PMID- 24305824
TI  - Membrane-anchored Abeta accelerates amyloid formation and exacerbates amyloid
      associated toxicity in mice.
AB  - Pathological, genetic, and biochemical hallmarks of Alzheimer's disease (AD) are
      linked to amyloid-beta (Abeta) peptide aggregation. Especially misfolded Abeta42
      peptide is sufficient to promote amyloid plaque formation. However, the cellular
      compartment facilitating the conversion of monomeric Abeta to aggregated toxic
      Abeta species remains unknown. In vitro models suggest lipid membranes to be the
      driving force of Abeta conversion. To this end, we generated two novel mouse
      models, expressing either membrane-anchored or nonanchored versions of the human
      Abeta42 peptide. Strikingly, membrane-anchored Abeta42 robustly accelerated Abeta
      deposition and exacerbated amyloid-associated toxicity upon crossing with Abeta
      precursor protein transgenic mice. These in vivo findings support the hypothesis
      that Abeta-membrane interactions play a pivotal role in early-onset AD as well as
      neuronal damage and provide evidence to study Abeta-membrane interactions as
      therapeutic targets. 

PMID- 24305823
TI  - Neuronal clearance of amyloid-beta by endocytic receptor LRP1.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly
      population. Accumulation, aggregation, and deposition of amyloid-beta (Abeta)
      peptides generated through proteolytic cleavage of amyloid precursor protein
      (APP) are likely initiating events in the pathogenesis of AD. While Abeta
      production is accelerated in familial AD, increasing evidence indicates that
      impaired clearance of Abeta is responsible for late-onset AD. Because Abeta is
      mainly generated in neurons, these cells are predicted to have the highest risk
      of encountering Abeta among all cell types in the brain. However, it is still
      unclear whether they are also involved in Abeta clearance. Here we show that
      receptor-mediated endocytosis in neurons by the low-density lipoprotein receptor
      related protein 1 (LRP1) plays a critical role in brain Abeta clearance. LRP1 is
      known to be an endocytic receptor for multiple ligands including Abeta.
      Conditional knock-out of Lrp1 in mouse forebrain neurons leads to increased brain
      Abeta levels and exacerbated amyloid plaque deposition selectively in the cortex
      of amyloid model APP/PS1 mice without affecting Abeta production. In vivo
      microdialysis studies demonstrated that Abeta clearance in brain interstitial
      fluid is impaired in neuronal Lrp1 knock-out mice. Because the neuronal LRP1
      deletion did not affect the mRNA levels of major Abeta degrading enzymes,
      neprilysin and insulin-degrading enzyme, the disturbed Abeta clearance is likely
      due to the suppression of LRP1-mediated neuronal Abeta uptake and degradation.
      Together, our results demonstrate that LRP1 plays an important role in receptor
      mediated clearance of Abeta and indicate that neurons not only produce but also
      clear Abeta. 

PMID- 24305825
TI  - Regulation of spine formation by ErbB4 in PV-positive interneurons.
AB  - The trophic factor neuregulin 1 (Nrg1) and its receptor ErbB4 are schizophrenia
      candidate genes. NRG1-ErbB4 signaling was thought to regulate spine formation and
      function in a cell-autonomous manner. Yet, recent studies indicate that ErbB4
      expression is largely restricted to GABAergic interneurons and is very low or
      absent in pyramidal cells. Here, we generated and characterized cell type
      specific ErbB4 mutant and transgenic mice. Spine density and the number of
      excitatory synapses were unaltered by neither deletion nor overexpression of
      ErbB4 in pyramidal neurons. However, spine density and excitatory synapse number
      were reduced in PV-ErbB4(-/-) mice where ErbB4 was selectively ablated in
      parvalbumin-positive GABAergic interneurons. Concurrently, basal glutamate
      transmission was impaired in PV-ErbB4(-/-) mice, but not in mice where ErbB4 was
      deleted or overexpressed in pyramidal neurons. Our results demonstrate a role of
      ErbB4 in PV-positive interneurons for spine formation in excitatory neurons. 

PMID- 24305826
TI  - Hippocampus and retrosplenial cortex combine path integration signals for
      successful navigation.
AB  - The current study used fMRI in humans to examine goal-directed navigation in an
      open field environment. We designed a task that required participants to encode
      survey-level spatial information and subsequently navigate to a goal location in
      either first person, third person, or survey perspectives. Critically, no
      distinguishing landmarks or goal location markers were present in the
      environment, thereby requiring participants to rely on path integration
      mechanisms for successful navigation. We focused our analysis on mechanisms
      related to navigation and mechanisms tracking linear distance to the goal
      location. Successful navigation required translation of encoded survey-level map
      information for orientation and implementation of a planned route to the goal.
      Our results demonstrate that successful first and third person navigation trials
      recruited the anterior hippocampus more than trials when the goal location was
      not successfully reached. When examining only successful trials, the
      retrosplenial and posterior parietal cortices were recruited for goal-directed
      navigation in both first person and third person perspectives. Unique to first
      person perspective navigation, the hippocampus was recruited to path integrate
      self-motion cues with location computations toward the goal location. Last, our
      results demonstrate that the hippocampus supports goal-directed navigation by
      actively tracking proximity to the goal throughout navigation. When using path
      integration mechanisms in first person and third person perspective navigation,
      the posterior hippocampus was more strongly recruited as participants approach
      the goal. These findings provide critical insight into the neural mechanisms by
      which we are able to use map-level representations of our environment to reach
      our navigational goals. 

PMID- 24305827
TI  - beta-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons
      by acting as an agonist for the G-protein-coupled receptor FFA3.
AB  - Free fatty acids receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43), for which the
      short-chain fatty acids (SCFAs) acetate and propionate are agonist, have emerged
      as important G-protein-coupled receptors influenced by diet and gut flora
      composition. A recent study (Kimura et al., 2011) demonstrated functional
      expression of FFA3 in the rodent sympathetic nervous system (SNS) providing a
      potential link between nutritional status and autonomic function. However, little
      is known of the source of endogenous ligands, signaling pathways, or effectors in
      sympathetic neurons. In this study, we found that FFA3 and FFA2 are unevenly
      expressed in the rat SNS with higher transcript levels in prevertebral (e.g.,
      celiac-superior mesenteric and major pelvic) versus paravertebral (e.g., superior
      cervical and stellate) ganglia. FFA3, whether heterologously or natively
      expressed, coupled via PTX-sensitive G-proteins to produce voltage-dependent
      inhibition of N-type Ca(2+) channels (Cav2.2) in sympathetic neurons. In addition
      to acetate and propionate, we show that beta-hydroxybutyrate (BHB), a metabolite
      produced during ketogenic conditions, is also an FFA3 agonist. This contrasts
      with previous interpretations of BHB as an antagonist at FFA3. Together, these
      results indicate that endogenous BHB levels, especially when elevated under
      certain conditions, such as starvation, diabetic ketoacidosis, and ketogenic
      diets, play a potentially important role in regulating the activity of the SNS
      through FFA3. 

PMID- 24305828
TI  - A computational model for epidural electrical stimulation of spinal sensorimotor
      circuits.
AB  - Epidural electrical stimulation (EES) of lumbosacral segments can restore a range
      of movements after spinal cord injury. However, the mechanisms and neural
      structures through which EES facilitates movement execution remain unclear. Here,
      we designed a computational model and performed in vivo experiments to
      investigate the type of fibers, neurons, and circuits recruited in response to
      EES. We first developed a realistic finite element computer model of rat
      lumbosacral segments to identify the currents generated by EES. To evaluate the
      impact of these currents on sensorimotor circuits, we coupled this model with an
      anatomically realistic axon-cable model of motoneurons, interneurons, and
      myelinated afferent fibers for antagonistic ankle muscles. Comparisons between
      computer simulations and experiments revealed the ability of the model to predict
      EES-evoked motor responses over multiple intensities and locations. Analysis of
      the recruited neural structures revealed the lack of direct influence of EES on
      motoneurons and interneurons. Simulations and pharmacological experiments
      demonstrated that EES engages spinal circuits trans-synaptically through the
      recruitment of myelinated afferent fibers. The model also predicted the capacity
      of spatially distinct EES to modulate side-specific limb movements and, to a
      lesser extent, extension versus flexion. These predictions were confirmed during
      standing and walking enabled by EES in spinal rats. These combined results
      provide a mechanistic framework for the design of spinal neuroprosthetic systems
      to improve standing and walking after neurological disorders. 

PMID- 24305829
TI  - Atp6ap2/(pro)renin receptor interacts with Par3 as a cell polarity determinant
      required for laminar formation during retinal development in mice.
AB  - (Pro)renin receptor [(P)RR], also known as Atp6ap2, has attracted growing
      attention as a key molecule for tissue renin-angiotensin system (RAS). In
      addition to its role in tissue RAS activation, Atp6ap2/(P)RR was originally
      identified as an accessory subunit for vacuolar H(+)-ATPase (v-ATPase), which is
      a multisubunit proton pump involved in diverse and fundamental cellular
      physiology. In this study, to elucidate the physiological function of
      Atp6ap2/(P)RR during retinal development in mammals, we used Cre-LoxP system to
      generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a
      critical role of Atp6ap2/(P)RR in photoreceptor development. Deletion of
      photoreceptor Atp6ap2/(P)RR did not affect retinal cell differentiation, but led
      to laminar disorganization around the outer nuclear layer together with severe
      dysfunction of photoreceptor cells. In the CKO mice, cell adhesion and polarity
      molecules, some of which were colocalized with Atp6ap2/(P)RR at the apical edge
      of the wild-type developing retina, were substantially dispersed together with
      mislocalization of retinal progenitor cells apart from the apical surface. Among
      theses molecules, coimmunoprecipitation using retinal homogenates and
      ATP6AP2/(P)RR-transfected cells showed that Atp6ap2/(P)RR interacted with
      partitioning defective 3 homolog (PAR3) protein, which is known to function in
      the Par-atypical protein kinase C (aPKC) system. Furthermore, yeast two-hybrid
      assays demonstrated direct molecular interaction between ATP6AP2/(P)RR and PAR3.
      Our present data revealed the novel function of Atp6ap2/(P)RR required for
      laminar formation during retinal development. We propose that this cellular
      activity associated with the Par-aPKC system, in addition to the v-ATPase
      function and tissue RAS activation, is the third biological role of
      Atp6ap2/(P)RR. 

PMID- 24305830
TI  - The visual representation of 3D object orientation in parietal cortex.
AB  - An accurate representation of three-dimensional (3D) object orientation is
      essential for interacting with the environment. Where and how the brain visually
      encodes 3D object orientation remains unknown, but prior studies suggest the
      caudal intraparietal area (CIP) may be involved. Here, we develop rigorous
      analytical methods for quantifying 3D orientation tuning curves, and use these
      tools to the study the neural coding of surface orientation. Specifically, we
      show that single neurons in area CIP of the rhesus macaque jointly encode the
      slant and tilt of a planar surface, and that across the population, the
      distribution of preferred slant-tilts is not statistically different from
      uniform. This suggests that all slant-tilt combinations are equally represented
      in area CIP. Furthermore, some CIP neurons are found to also represent the third
      rotational degree of freedom that determines the orientation of the image pattern
      on the planar surface. Together, the present results suggest that CIP is a
      critical neural locus for the encoding of all three rotational degrees of freedom
      specifying an object's 3D spatial orientation. 

PMID- 24305831
TI  - Independent population coding of speech with sub-millisecond precision.
AB  - To understand the strategies used by the brain to analyze complex environments,
      we must first characterize how the features of sensory stimuli are encoded in the
      spiking of neuronal populations. Characterizing a population code requires
      identifying the temporal precision of spiking and the extent to which spiking is
      correlated, both between cells and over time. In this study, we characterize the
      population code for speech in the gerbil inferior colliculus (IC), the hub of the
      auditory system where inputs from parallel brainstem pathways are integrated for
      transmission to the cortex. We find that IC spike trains can carry information
      about speech with sub-millisecond precision, and, consequently, that the temporal
      correlations imposed by refractoriness can play a significant role in shaping
      spike patterns. We also find that, in contrast to most other brain areas, the
      noise correlations between IC cells are extremely weak, indicating that spiking
      in the population is conditionally independent. These results demonstrate that
      the problem of understanding the population coding of speech can be reduced to
      the problem of understanding the stimulus-driven spiking of individual cells,
      suggesting that a comprehensive model of the subcortical processing of speech may
      be attainable in the near future. 

PMID- 24305832
TI  - Memory consolidation by replay of stimulus-specific neural activity.
AB  - Memory consolidation transforms initially labile memory traces into more stable
      representations. One putative mechanism for consolidation is the reactivation of
      memory traces after their initial encoding during subsequent sleep or waking
      state. However, it is still unknown whether consolidation of individual memory
      contents relies on reactivation of stimulus-specific neural representations in
      humans. Investigating stimulus-specific representations in humans is particularly
      difficult, but potentially feasible using multivariate pattern classification
      analysis (MVPA). Here, we show in healthy human participants that stimulus
      specific activation patterns can indeed be identified with MVPA, that these
      patterns reoccur spontaneously during postlearning resting periods and sleep, and
      that the frequency of reactivation predicts subsequent memory for individual
      items. We conducted a paired-associate learning task with items and spatial
      positions and extracted stimulus-specific activity patterns by MVPA in a
      simultaneous electroencephalography and functional magnetic resonance imaging
      (fMRI) study. As a first step, we investigated the amount of fMRI volumes during
      rest that resembled either one of the items shown before or one of the items
      shown as a control after the resting period. Reactivations during both awake
      resting state and sleep predicted subsequent memory. These data are first
      evidence that spontaneous reactivation of stimulus-specific activity patterns
      during resting state can be investigated using MVPA. They show that reactivation
      occurs in humans and is behaviorally relevant for stabilizing memory traces
      against interference. They move beyond previous studies because replay was
      investigated on the level of individual stimuli and because reactivations were
      not evoked by sensory cues but occurred spontaneously. 

PMID- 24305834
TI  - Susceptibility to vole attacks due to bark phenols and terpenes inPinus contorta
      provenances introduced into Sweden.
AB  - Seedlings of North AmericanPinus contorta introduced to Sweden and Finland are
      severely gnawed by voles, e.g.,Microtus agrestis. The level of damage varies
      between provenances. Chemical analyses of various phenolic compounds,
      monoterpenes, and resin acids of different provenances and of damaged and
      undamaged stems showed that some phenolic substances in the bark increased after
      damage without deterring the animals, that monoterpene differences between
      provenances were not related to vole damage, and that certain resin acids
      occurred in larger amounts in lightly than in severely damaged provenances.
      Levopimaric and neoabietic acid, and possibly abietic acid, may be important for
      a partial resistance to vole browsing. 

PMID- 24305833
TI  - Long-term antagonism of kappa opioid receptors prevents escalation of and
      increased motivation for heroin intake.
AB  - The abuse of opioid drugs, both illicit and prescription, is a persistent problem
      in the United States, accounting for >1.2 million users who require treatment
      each year. Current treatments rely on suppressing immediate withdrawal symptoms
      and replacing illicit drug use with long-acting opiate drugs. However, the
      mechanisms that lead to preventing opiate dependence are still poorly understood.
      We hypothesized that kappa opioid receptor (KOR) activation during chronic opioid
      intake contributes to negative affective states associated with withdrawal and
      the motivation to take increasing amounts of heroin. Using a 12 h long-access
      model of heroin self-administration, rats showed escalation of heroin intake over
      several weeks. This was prevented by a single high dose (30 mg/kg) of the long
      acting KOR antagonist norbinaltorphimine (nor-BNI), paralleled by reduced
      motivation to respond for heroin on a progressive-ratio schedule of
      reinforcement, a measure of compulsive-like responding. Systemic nor-BNI also
      significantly decreased heroin withdrawal-associated anxiety-like behavior.
      Immunohistochemical analysis showed prodynorphin content increased in the nucleus
      accumbens core in all heroin-exposed rats, but selectively increased in the
      nucleus accumbens shell in long-access rats. Local infusion of nor-BNI (4
      MUg/side) into accumbens core altered the initial intake of heroin but not the
      rate of escalation, while local injection into accumbens shell selectively
      suppressed increases in heroin intake over time without altering initial intake.
      These data suggest that dynorphin activity in the nucleus accumbens mediates the
      increasing motivation for heroin taking and compulsive-like responding for
      heroin, suggesting that KOR antagonists may be promising targets for the
      treatment of opioid addiction. 

PMID- 24305835
TI  - Sex-specific production of ipsdienol and myrcenol byDendroctonus ponderosae
      (Coleoptera: Scolytidae) exposed to myrcene vapors.
AB  - Male mountain pine beetles,Dendroctonus ponderosae Hopkins, produced ipsdienol
      [97.0% +/- 0.3S-(+)] and myrcenol (90.3% +/- 4.0E) when exposed to myrcene
      vapors. Females which were exposed to myrcene vapors did not produce any
      ipsdienol, but did produce low levels of myrcenol (98.0% +/- 0.7E). Neither sex
      produced detectable levels of ipsdienol or myrcenol when fed for 24 hr on
      lodgepole pine,Pinus contorta var.latifolia Engelmann. The sex-specific
      conversion of myrcene to ipsdienol and myrcenol suggests that these compounds may
      have behavioral significance within the species. In addition, the S-(+)-ipsdienol
      produced by maleD. ponderosae probably functions as a repellent allomone
      againstIps pini (Say). 

PMID- 24305836
TI  - Interspecific activity of semiochemicals among sibling species ofPissodes
      (Coleoptera: Curculionidae).
AB  - Pissodes strobi, P. approximatus, andP. nemorensis are sibling species of pine
      weevils that can hybridize in the laboratory but are presumed to be
      reproductively isolated in nature. Males of all three species produce the
      terpenoids grandisol and grandisal; these compounds serve as an aggregation
      pheromone forP. approximatus andP. nemorensis when deployed with odors from pine
      bolts. A series of field experiments examined the possibility of cross-attraction
      among the three species. Tests in New York and Florida found that parapatrically
      distributedP. approximatus andP. nemorensis were cross-attractive, but different
      photoperiodic conditioning was required for pheromone production in males of the
      two species. Long-day pheromone production (P. approximatus-type.) was inherited
      in interspecific hybrids. Other tests showed thatP. strobi males, or hybrid males
      from crosses ofP. strobi withP. approximatus, were not attractive to sympatricP.
      approximatus. When the response ofP. strobi was assessed to males of eitherP.
      strobi orP. approximatus confined on white pine leaders (the breeding site ofP.
      strobi), no evidence of cross-attraction or pheromone activity was found;P.
      strobi were caught in equal numbers onP. strobi-baited leaders,P. approximatus
      baited leaders, and unbaited leaders. Tests of interspecific interactions found
      that maleP. strobi produce an allelochemical signal that interrupts the response
      ofP. approximatus to its natural or synthetic aggregation pheromone. This
      interspecific response is apparently adaptive for members of both species
      (classified as an allomone-kairomone or synomone) because it may ultimately serve
      to prevent interspecific matings that would lower the fitness of the parents. 

PMID- 24305837
TI  - Electroantennogram responses by mountain pine beetles,Dendroctonus ponderosae
      Hopkins, exposed to selected semiochemicals.
AB  - Electroantennograms (EAGs) were obtained forD. ponderosae to the bark beetle
      pheromonestrans-verbenol,cis-verbenol,exo-brevicomin,endo-brevicomin, frontalin,
      verbenone; to the kairomones, alpha-pinene, beta-pinene, camphene, Delta-3
      carene, limonene, myrcene; to a blend (1?1?1) oftrans-verbenol,exo-brevicomin,
      and myrcene; and to diacetone-alcohol. Male and female responses, in general, did
      not differ significantly over the whole EAG dose-response curves but differed at
      a few concentrations on many of the curves. There were more differences noted for
      pheromones than kairomones. The blend yielded among the largest EAGs in both
      sexes and appeared to show synergism. Responses of females were lower than those
      for males in most instances. Significant differences in responses by the two
      sexes were much fewer for the kairomones than the pheromones. EAG recovery rates
      tested at only one concentration showed significant differences between males and
      females for three pheromones,trans-verbenol,cis-verbenol, and verbenone, and two
      kairomones, camphene and Delta-3-carene. Thresholds were quite low for most of
      the odorants exceptcis-verbenol, camphene, verbenone, and diacetone-alcohol in
      females, andcis-verbenol, verbenone, alpha-pinene, and diacetone-alcohol in
      males. The results, using at least one EAG parameter, support behavioral and
      field studies involvingexo-brevicomin,trans-verbenol, frontalin, and the blend. 

PMID- 24305838
TI  - Pheromone-mediated copulatory responses of the screwworm fly,Cochliomyia
      hominivorax.
AB  - A bioassay based on male copulatory responses occurring on contact with dead
      decoy insects was used to confirm the existence of a sex pheromone in the
      screwworm fly,Cochliomyia hominivorax. Males responded to female but not male
      decoys. Mated and virgin females were equally stimulatory. Activity was abolished
      when females were washed with hexane but partially restored by treatment with
      crude hexane extract of females. Responses decreased when extracts were diluted
      and when the number of females extracted per milliliter of hexane was decreased
      from 20 to 1 in the preparation of extracts concentrated to 0.4 female/MUl.
      Sexually mature female decoys of the 009 strain, the most laboratory-adapted of
      three strains examined in intrastrain tests, produced few copulatory attempts
      compared with those of Aricruz or DE-9 strains. However, newly emerged 009 as
      well as Aricruz females elicited responses from about 80% of sexually mature
      males. Those of the DE-9 strain stimulated fewer than 1%. The observation that
      009 females were maximally stimulatory before becoming receptive to mating
      suggests that these strain differences resulted from laboratory colonization. 

PMID- 24305839
TI  - Diphenyl-benzo[1,3]dioxole-4-carboxylic acid pentafluorophenyl ester: a
      convenient catechol precursor in the synthesis of siderophore vectors suitable
      for antibiotic Trojan horse strategies.
AB  - Catechols are components of many metal-chelating compounds, including
      siderophores that are naturally occurring iron(III) chelators excreted by
      microorganisms. Catechol derivatives are poorly soluble in organic media and the
      synthesis of catechol-containing molecules requires the use of protected catechol
      precursors with improved organic solubility. We therefore developed 2,2-diphenyl
      benzo[1,3]dioxole-4-carboxylic acid pentafluorophenyl ester. This activated ester
      reacts with an amine functionalized scaffold to generate chelators in which the
      catechol functions are protected in the form of diphenyl-benzodioxole moieties.
      The catechol can subsequently be deprotected, at the end of the synthesis, with
      trifluoroacetic acid (TFA). This strategy was applied to the synthesis of two
      catechol compounds functionalized with a terminal propargyl extension. These two
      compounds were shown to promote iron uptake in Escherichia coli and Pseudomonas
      aeruginosa. These two compounds are suitable for use as vectors in antibiotic
      Trojan horse approaches, as they could be conjugated with azide-functionalized
      antibiotics using the Huisgen dipolar 1,3-cycloaddition.

PMID- 24305840
TI  - Resveratrol treatment during goat oocytes maturation enhances developmental
      competence of parthenogenetic and hand-made cloned blastocysts by modulating
      intracellular glutathione level and embryonic gene expression.
AB  - PURPOSE: The aim of the present study was to determine whether supplementation of
      resveratrol, a stilbenoid antioxidant with therapeutic significance, influences
      goat (Capra hircus) oocyte maturation and subsequent embryonic development and
      expression of apoptosis and early embryonic development-related genes. METHODS:
      Five different concentrations of resveratrol (0.1, 0.25, 0.5, 2.0 and 5.0 MUM)
      were used in in vitro maturation (IVM) medium. Cell tracker blue and 2',7'
      dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescent stains were used to
      assay intracellular glutathione and reactive oxygen species levels in mature
      oocytes. Parthenogenetic activation and hand-made cloning were performed to check
      the developmental potential following resveratrol treatment. We used quantitative
      real-time PCR to analyze embryonic gene expression. RESULT: Compared to control,
      no significant improvement was observed in nuclear maturation in resveratrol
      treated groups and at 5.0 MUM concentration maturation rate decreased
      significantly (P < 0.05). But resveratrol treatment at the concentrations of
      0.25, 0.5 MUM significantly reduced intracellular ROS, and increased GSH
      concentrations. Oocytes treated with 0.25, 0.5 MUM resveratrol when subsequently
      used for PA and HMC, higher extent of blastocyst yields were observed. Expression
      analysis of proapoptotic (Bax) gene in mature oocytes, cumulus cells, and HMC
      derived blastocysts revealed lesser transcript abundances in various resveratrol
      treated groups., however no change in the same was observed for antiapoptotic
      gene (Bcl2). Differential expression of genes associated with developmental
      competence and nuclear reprogramming was also observed in HMC-derived
      blastocysts. CONCLUSION: Our results show that resveratrol treatment at optimum
      concentrations (0.25 and 0.5 MUM) during IVM produced beneficial microenvironment
      within oocytes by increasing the intracellular GSH, decreasing ROS level and this
      in turn, stimulated embryonic development and regulated gene expression.

PMID- 24305841
TI  - Sinonasal natural killer/T-cell lymphoma presenting as pyrexia of unknown origin
      with nasal symptoms.
AB  - A 68-year-old Chinese man presented with an eight-month history of pyrexia of
      unknown origin and chronic sinusitis despite multiple courses of antibiotics. He
      underwent extensive investigations, including workups for infections, chronic
      granulomatous diseases and malignancy. Nasal biopsies were performed twice under
      local anaesthesia, but did not show any evidence of malignancy. Eventually, the
      patient was diagnosed with natural killer (NK)/T-cell lymphoma, nasal variant,
      based on histopathological findings from harvested deep tissue obtained via
      functional endoscopic sinus surgery. This study highlights that, for patients
      presenting with pyrexia of unknown origin and nasal symptoms, NK/T-cell lymphoma
      must be considered as a differential diagnosis. Generous amounts of tissue should
      be harvested under general anaesthesia rather than limited tissue under local
      anaesthesia, in order to facilitate and ensure a definitive diagnosis.

PMID- 24305842
TI  - Delayed presentation of port-site metastasis from an unknown gastrointestinal
      malignancy following laparoscopic cholecystectomy.
AB  - Port-site metastasis (PSM) is often encountered during laparoscopic surgery in
      patients with malignancy. We report a 45-year-old woman who presented with a
      single PSM from papillary adenocarcinoma after undergoing laparoscopic
      cholecystectomy for calculus cholecystitis. Post cholecystectomy, a diagnosis of
      chronic cholecystitis was confirmed on histopathology. The patient presented with
      a mass at the site of epigastric port 28 months after surgery. PSM was suspected
      on clinical examination, which was supported by findings on computed tomography
      and further confirmed by fine-needle aspiration cytology of the lump. The patient
      underwent surgical clearance of the mass, and histopathological examination
      proved the lesion to be papillary adenocarcinoma. The site of the primary tumour
      was not detected even after thorough examination. Based on the histopathology
      report following local surgical clearance, the patient was started on
      chemotherapy. This case is unusual because of the long delay prior to the
      presentation of PSM and the unknown primary malignancy.

PMID- 24305844
TI  - Participation without representation? Senior opinion, legislative behavior, and
      federal health reform.
AB  - Why do legislators sometimes engage in behavior that deviates from the expressed
      policy preferences of constituents who participate in politics at high rates? We
      examine this puzzle in the context of Democratic legislators' representation of
      their senior citizen constituents on the Patient Protection and Affordable Care
      Act of 2010 (ACA). We find that legislators' roll-call votes on the ACA did not
      reflect the stated preferences of their respective senior constituents; by
      contrast, these roll-call votes did reflect the preferences of nonsenior adults.
      We draw upon a theoretical framework developed by Mansbridge to explain this
      apparent nonresponsiveness to seniors on the ACA. This framework distinguishes
      between promissory representation, whereby legislators merely respond to
      constituents' preferences, and anticipatory representation, whereby legislators
      respond to constituents' underlying policy interests, even when such interests
      conflict with expressed preferences. By considering the Medicare provisions in
      the ACA and analyzing Democratic legislators' floor speeches on health reform, we
      provide preliminary evidence that members of Congress engaged in anticipatory
      representation of their senior constituents by attempting to educate seniors
      about how the ACA serves their policy interests. 

PMID- 24305845
TI  - Maternity leave duration and postpartum mental and physical health: implications
      for leave policies.
AB  - This study examines the association of leave duration with depressive symptoms,
      mental health, physical health, and maternal symptoms in the first postpartum
      year, using a prospective cohort design. Eligible employed women, eighteen years
      or older, were interviewed in person at three Minnesota hospitals while
      hospitalized for childbirth in 2001. Telephone interviews were conducted at six
      weeks (N = 716), twelve weeks (N = 661), six months (N = 625), and twelve months
      (N = 575) after delivery. Depressive symptoms (Edinburgh Postnatal Depression
      Scale), mental and physical health (SF-12 Health Survey), and maternal childbirth
      related symptoms were measured at each time period. Two-stage least squares
      analysis showed that the relationship between leave duration and postpartum
      depressive symptoms is U-shaped, with a minimum at six months. In the first
      postpartum year, an increase in leave duration is associated with a decrease in
      depressive symptoms until six months postpartum. Moreover, ordinary least squares
      analysis showed a marginally significant linear positive association between
      leave duration and physical health. Taking leave from work provides time for
      mothers to rest and recover from pregnancy and childbirth. Findings indicate that
      the current leave duration provided by the Family and Medical Leave Act, twelve
      weeks, may not be sufficient for mothers at risk for or experiencing postpartum
      depression.

PMID- 24305846
TI  - Once you know, you are responsible: the road from scholar to activist.
AB  - Conventional wisdom usually argues that academic research should be conducted
      with the highest level of objectivity possible. I seek to turn that argument on
      its head and suggest that taking sides, even pursuing activist tactics, in
      support of our subjects' goals may be not only desirable but also the most
      ethical option. Drawing on my own experiences with research and activism in
      HIV/AIDS, first in the United States and later in East Africa, I present the case
      for the mutually beneficial relationship between scholarship and activism. 

PMID- 24305847
TI  - Voucherizing Medicare.
AB  - This article explores the evolving language of Medicare reform and recent
      conflicts over "voucherizing" Medicare. The Medicare reform debate is, in part, a
      contest over how to frame policy alternatives in order to enhance (or diminish)
      their political viability. "Voucherizing" has emerged as a powerful rhetorical
      weapon in that fight. Yet the accompanying debate is often misleading about both
      the current state of Medicare and the necessity of altering its programmatic
      structure to ensure future stability. 

PMID- 24305843
TI  - New tools and new biology: recent miniaturized systems for molecular and cellular
      biology.
AB  - Recent advances in applied physics and chemistry have led to the development of
      novel microfluidic systems. Microfluidic systems allow minute amounts of reagents
      to be processed using MUm-scale channels and offer several advantages over
      conventional analytical devices for use in biological sciences: faster, more
      accurate and more reproducible analytical performance, reduced cell and reagent
      consumption, portability, and integration of functional components in a single
      chip. In this review, we introduce how microfluidics has been applied to
      biological sciences. We first present an overview of the fabrication of
      microfluidic systems and describe the distinct technologies available for
      biological research. We then present examples of microsystems used in biological
      sciences, focusing on applications in molecular and cellular biology. 

PMID- 24305848
TI  - Going for the cure: patient interest groups and health advocacy in the United
      States.
AB  - Citizen groups, though celebrated during their sudden arrival on the lobbying
      scene, are vastly outnumbered by groups representing elite, occupationally based
      interests. Sensitive to the odds that nonoccupational groups face, this study
      asks what factors have allowed patient groups to form and become active in
      federal politics. Using three distinct data sets--a survey of patient groups,
      content analysis of group websites, and in-depth interviews with group
      representatives and policy makers in Washington, DC--this study assesses the
      activities of patient groups in the United States and argues that patient
      advocacy organizations garner stability from the relatively easy provision of
      selective and solidary benefits. Larger patient groups are especially likely to
      make use of these structural advantages to pursue congressional lobbying
      strategies. However, even these groups seek out noncompetitive, distributive
      political environments. Moreover, the study finds that patient groups rarely form
      coalitions across diseases, forgoing the potential to collectively speak for
      shared patient interests.

PMID- 24305849
TI  - Essential health benefits and the Affordable Care Act: law and process.
AB  - Starting in 2014, the Affordable Care Act (ACA) will require private insurance
      plans sold in the individual and small-group markets to cover a roster of
      "essential health benefits." Precisely which benefits should count as essential,
      however, was left to the discretion of the Department of Health and Human
      Services (HHS). The matter was both important and controversial. Nonetheless, HHS
      announced its policy by posting on the Internet a thirteen-page bulletin stating
      that it would allow each state to define essential benefits for itself. On both
      substance and procedure, the move was surprising. The state-by-state approach
      departed from the uniform, federal standard that the ACA appears to anticipate
      and that informed observers expected HHS to adopt. And announcing the policy
      through an Internet bulletin appeared to allow HHS to sidestep traditional
      administrative procedures, including notice and comment, immediate review in the
      courts, and White House oversight. This article explores two questions. First, is
      the state-by-state approach a lawful exercise of HHS's authority? Second, did HHS
      in fact evade the procedural obligations that are meant to shape the exercise of
      its discretion? 

PMID- 24305850
TI  - Splenic FDG uptake predicts poor prognosis in patients with unresectable
      cholangiocarcinoma.
AB  - AIM: Diffuse splenic 18F-Fluorodeoxyglucose (FDG) uptake has shown to be
      associated with concurrent inflammation. We evaluated the prognostic value of
      diffuse splenic FDG uptake for predicting prognosis in cholangiocarcinoma
      patients. PATIENTS, METHODS: Sixty-four patients with unresectable
      cholangiocarcinoma performed Positron emission tomography/computed tomography
      (PET/CT) using FDG between July 2009 and April 2012. Patients were divided into
      two groups according to splenic FDG uptake relative to hepatic FDG uptake. Eleven
      patients showing splenic FDG uptake exceeding hepatic uptake were included in
      group A, while 53 patients with hepatic FDG uptake exceeding splenic uptake were
      included in group B. Prognostic factors for overall survival were evaluated using
      log-rank test. Variables with a probability of less than or equal to 0.1 on
      univariate analysis were considered as possible independent factors. Cox
      proportional hazards model was used to analyze univariate and multivariate
      analysis. RESULTS: Mean standardized uptake value of the liver (Liver
      SUVmean)/Spleen SUVmean (L/S) ratio <1 (p = 0.0034), WBC > 10 000 (p = 0.1155)
      and CEA >30 (p = 0.0946) were predictors of overall survival on univariate
      analysis. In a subsequent multivariate analysis, L/S ratio <1 remained a
      significant independent predictor of poor prognosis (HR 6.0153, 95% CI, 1.7193
      21.0460, p = 0.0052). CONCLUSION: Our study has shown that splenic FDG uptake
      could be a predictor of overall survival of unresectable cholangiocarcinoma
      patients.

PMID- 24305851
TI  - Absence of DNA damage after 60-Hz electromagnetic field exposure combined with
      ionizing radiation, hydrogen peroxide, or c-Myc overexpression.
AB  - The principal objective of this study was to assess the DNA damage in a normal
      cell line system after exposure to 60 Hz of extremely low frequency magnetic
      field (ELF-MF) and particularly in combination with various external factors, via
      comet assays. NIH3T3 mouse fibroblast cells, WI-38 human lung fibroblast cells,
      L132 human lung epithelial cells, and MCF10A human mammary gland epithelial cells
      were exposed for 4 or 16 h to a 60-Hz, 1 mT uniform magnetic field in the
      presence or absence of ionizing radiation (IR, 1 Gy), H(2)O(2) (50 MUM), or c-Myc
      oncogenic activation. The results obtained showed no significant differences
      between the cells exposed to ELF-MF alone and the unexposed cells. Moreover, no
      synergistic or additive effects were observed after 4 or 16 h of pre-exposure to
      1 mT ELF-MF or simultaneous exposure to ELF-MF combined with IR, H(2)O(2), or c
      Myc activation.

PMID- 24305852
TI  - Design of a structure with low incident and viewing angle dependence inspired by
      Morpho butterflies.
AB  - Morpho butterflies are well known for their brilliant iridescent colors, which
      arise from periodic arrays of scales. These brilliant colors have a low angle
      dependence, in contrast to similar phenomena that are commonly caused by the
      periodic structures. We designed a structure with a low incident and viewing
      angle dependence inspired by Morpho butterflies. This structure was studied using
      the finite-difference time-domain method. The lamellae distribution of tree-like
      structure was found to be the determining factor for producing a low incident
      angle dependence. Two advanced models were designed to produce a low viewing
      angle dependence. Model I was constructed using two layers of scales. The
      particle swarm optimization algorithm was used to construct Model II. The angle
      dependence of Model II exhibited a large viewing angle range under various
      incident angles. 

PMID- 24305853
TI  - The effect of B-chromosomes of rye on the chromosome association in F1 hybrids
      Triticum aestivum x Secale cereale in the absence of chromosomes 5B or 5D.
AB  - T. aestivum var. 'Chinese Spring' (monosomic 5B and 5D, respectively) was crossed
      with S. cereale (with and without B-chromosomes). The resulting nullisomic 5B
      hybrids exhibited a high degree of chromosome association both at 20 degrees C
      and 10 degrees C. The presence of B-chromosomes reduced association slightly
      whether 5B was present or not.In nullisomic 5D hybrids B-chromosomes of rye raise
      chromosome association at 20 degrees C when compared to hybrids with 5D, with as
      well as without, B's. At 10 degrees C, due to the absence of the Ltp gene on 5D,
      chromosome association in nullisomic 5D hybrids is low, and no effects of rye B
      chromosomes is detectable.The hypothesis that B-chromosomes of rye carry (an)
      asynaptic gene(s) decreasing effective pairing, and (an) independent post
      synaptic gene(s) increasing chiasma frequency on effective pairing sites, is
      presented. 

PMID- 24305854
TI  - Analysis of genetic changes in radiated and non-radiated bulk oat (Avena sativa
      L.) populations.
AB  - In both radiated and non-radiated oat populations inbreeding coefficients
      increased more slowly than was expected on the assumption of full selfing and
      equal selective values for homozygotes and heterozygotes. Assuming 1% outcrossing
      for oats and a selective value of 1.0 for the mean, the heterozygotes for two
      loci governing crown rust reaction have an advantage of 50% over the homozygotes.
      This study supports previous observations that the heterozygote often has a
      decided advantage in predominantly self-pollinated crops. 

PMID- 24305855
TI  - The expression of tumour markers in intraspecific somatic hybrids of normal and
      crown gall cells from Nicotiana tabacum.
AB  - Following fusion of protoplasts from crown gall tumour calli, characterized by
      hormone independent growth, and protoplasts from normal tissues of a streptomycin
      resistant mutant, SR1, we selected hormone independent streptomycin-resistant
      calli in Nicotiana tabacum. The tumour line, B6S3, lost the ability to form
      shoots. Some of the selected lines, similar to SR1, however, are morphogenic.
      Both calli and shoots contained the tumour specific enzyme lysopinedehydrogenase.
      The hybrid shoots are resistant to Agrobacterium infection and do not root. These
      tumorous properties are dominantly expressed in the somatic hybrids. 

PMID- 24305856
TI  - Genetics of esterases in species of Lycopersicon.
AB  - Improvements in plant culture and electrophoretic technique permit detection and
      genetic analysis of seven esterase loci in Lycopersicon esculentum and related
      species with homosequential chromosomes. At all of these loci except one, each
      allele codes for a single anodal band, and the electrophoretic variants are
      inherited in monogenic fashion. For the exceptional Est-4, allozymes are 1-3
      banded in various combinations at four positions, and rare recombinants in one
      cross appeared at a frequency of 0.0005, suggesting the existence of several very
      tightly linked genes. Est-2 segregated solely for intensity differences in
      dominant/recessive fashion; Est-3 and Est-4 behave as monomers; the remaining Est
      l, 5, 6, and 7 - coding for contiguous bands in the region closest to the origin 
      are dimeric. The latter group are tightly linked inter se in the proximal
      portion of 2L (long arm of chromosome 2), the total map distance of the complex
      being approximately 1.5 cM; Est-2 is situated on 9L between ah and marm; Est-3 on
      1L between inv and dgt; Est-4 has not yet been located. Even in the interspecific
      hybrids, map distances are similar to the standard values for L. esculentum.
      Tandem duplication is hypothesized for the origin of the Est-l, 5-7 complex,
      which adds another example to the growing list of linked mimic genes in the
      tomato genome. In respect to the position of their bands and tight inter se
      linkage, this series exactly parallels the EA, EB, EC esterase series in Hordeum
      vulgare - a fact which suggests great antiquity for this block of genes. 

PMID- 24305857
TI  - Production of trigeneric (barley * wheat) * rye hybrids.
AB  - Rye (Secale cereale cv. Prolific 2n=14 and 2n =14 + 2B was crossed onto hybrids
      between barley (Hordeum vulgare 2n = 14) and wheat (Triticum aestivum 2n= 42).
      Pollinated florets were injected with GA3 to promote fertilization and hybrid
      embryo development. At 16 days after pollination the watery caryopses were
      removed, embryos dissected and cultured on a modified B5 medium. Approximately
      20% of the cultured embryos produced both roots and coleoptile and developed into
      viable seedlings. Viable seeds were also obtained at a low frequency from the
      same cross combinations. The hybrids were wheat-like except for the hairy neck
      characteristic of rye. There were 35 chromosomes in somatic tissue; 21 wheat, 7
      barley and 7 rye. The rye chromosomes were distinguishable by their larger size
      and terminal C-bands. A lower seed set was obtained using pollen from rye plants
      with 2n=14 + 2B chromosomes than from plants without B chromosomes. 

PMID- 24305858
TI  - A method of parental selection and cross prediction using incomplete partial
      diallels : Part 1: a simulation study.
AB  - When a character has a large additive genetic component in its variance, general
      combining ability estimates may be used for predicting cross performance.
      Further, if emphasis is placed on the ranks of the general combining abilities in
      a diallel rather than on their numerical values, the incomplete partial diallel
      is a powerful tool for parental selection. In a self pollinating species, if
      general combining ability effects are equal to or greater than specific combining
      ability effects, 20% of the partial diallel is found to give enough information
      for accurate ranking of the parental general combining abilities. A generalised
      method for calculating general combining abilities from incomplete partial
      diallels is presented and tested by computer simulation over a large range of
      genetic population parameters. 

PMID- 24305859
TI  - Inheritance of seed protein content and other agronomic characters in long bean
      (Vigna sesquipedalis Fruw.).
AB  - Seven varieties of long bean, which included three local and four exotic, were
      crossed in a complete diallel. This was an attempt to study the inheritance of
      crude protein content, protein yield, flowering date, pod yield and yield
      components.Both additive and non-additive gene effects were responsible for the
      genetic variation in the diallel population. However, dominance variance was more
      important than additive variance in crude protein content, number of pods per
      plant and number of seeds per pod. For seed weight and pod length, additive
      variance was more important.The crude protein content, protein yield and number
      of pods per plant appeared to be controlled by overdominance effects. Partial
      dominance seemed to be the case for flowering date, pod length and seed weight;
      complete to overdominance for pod yield. High protein appeared to be associated
      with recessive genes whereas there was a general trend of high yielding parents
      carrying more dominant genes. 

PMID- 24305861
TI  - Fruit removal rate depends on neighborhood fruit density, frugivore abundance,
      and spatial context.
AB  - Fleshy-fruited plants depend fundamentally on interactions with frugivores for
      effective seed dispersal. Recent models of frugivory within spatially explicit
      networks make two general predictions regarding these interactions: rate of fruit
      removal increases (i.e., is facilitated) as densities of conspecific neighborhood
      fruits increase, and fruit removal rate varies positively with frugivore
      abundance. We conducted a field experiment that constitutes the first empirical
      and simultaneous test of these two primary predictions. We manipulated
      neighborhood abundances of arrowwood (Viburnum recognitum and Viburnum dentatum)
      fruits in southern New England's maritime shrub community and monitored removal
      rates by autumn-migrating birds. Focal arrowwood plants in neighborhoods with
      high conspecific fruit density sustained moderately decreased fruit removal rates
      (i.e., competition) relative to those in low-density neighborhoods, a result that
      agrees with most field research to date but contrasts with theoretical
      expectation. We suggest the spatial contexts that favor competition (i.e., high
      abundance neighborhoods and highly aggregated landscapes) are considerably more
      common than the relatively uniform, low-aggregation fruiting landscapes that
      promote facilitation. Patterns of arrowwood removal by avian frugivores generally
      varied positively with, and apparently in response to, seasonal changes in
      migratory frugivore abundance. However, we suggest that dense stands of arrowwood
      concentrated frugivore activity at the neighborhood scale, thus counteracting
      geographic patterns of frugivore abundance. Our results underscore the importance
      of considering spatial context (e.g., fruit distribution and aggregation,
      frugivory hubs) in plant-avian frugivore interactions. 

PMID- 24305862
TI  - Transplantation of subalpine wood-pasture turfs along a natural climatic gradient
      reveals lower resistance of unwooded pastures to climate change compared to
      wooded ones.
AB  - Climate change could impact strongly on cold-adapted mountain ecosystems, but
      little is known about its interaction with traditional land-use practices. We
      used an altitudinal gradient to simulate a year-round warmer and drier climate
      for semi-natural subalpine grasslands across a landscape of contrasting land-use
      management. Turf mesocosms from three pasture-woodland land-use types-unwooded
      pasture, sparsely wooded pasture, and densely wooded pasture-spanning a gradient
      from high to low management intensity were transplanted downslope to test their
      resistance to two intensities of climate change. We found strong overall effects
      of intensive (+4 K) experimental climate change (i.e., warming and reduced
      precipitation) on plant community structure and function, while moderate (+2 K)
      climate change did not substantially affect the studied land-use types, thus
      indicating an ecosystem response threshold to moderate climate perturbation. The
      individual land-use types were affected differently under the +4 K scenario, with
      a 60% decrease in aboveground biomass (AGB) in unwooded pasture turfs, a 40%
      decrease in sparsely wooded pasture turfs, and none in densely wooded ones.
      Similarly, unwooded pasture turfs experienced a 30% loss of species, advanced (by
      30 days) phenological development, and a mid-season senescence due to drought
      stress, while no such effects were recorded for the other land-use types. The
      observed contrasting effects of climate change across the pasture-woodland
      landscape have important implications for future decades. The reduced impact of
      climate change on wooded pastures as compared to unwooded ones should promote the
      sustainable land use of wooded pastures by maintaining low management intensity
      and a sparse forest canopy, which buffer the immediate impacts of climate change
      on herbaceous vegetation.

PMID- 24305863
TI  - Resin duct characteristics associated with tree resistance to bark beetles across
      lodgepole and limber pines.
AB  - Bark beetles have recently killed billions of trees, yet conifer defenses are
      formidable and some trees resist attack. A primary anti-insect defense of pines
      is oleoresin from a system of resin ducts throughout the tree. Resin defense
      traits are heritable, and evidence suggests that resin duct characteristics are
      associated with resistance to insects. However, comparisons of resin ducts in
      trees killed by bark beetles to trees that resisted attack are unavailable. We
      compared vertical resin duct characteristics (number, density, and size) and
      growth rates from trees that were "resistant" (survived mass attack) versus
      "susceptible" (killed by attack) to bark beetles in lodgepole (Pinus contorta)
      and limber (Pinus flexilis) pines. Resistant trees of both species had
      significantly more resin ducts in recent growth than susceptible trees.
      Discriminant analysis (DA) correctly categorized 84% of lodgepole and 92% of
      limber pines as susceptible/resistant based on combinations of resin duct and
      growth characteristics from recent 5- through 20-year growth intervals. DA models
      using measures from only the most recent 5 years of growth correctly categorized
      72 and 81% of lodgepole and limber pines, respectively. Comparing resistant to
      susceptible trees independent of species identity led to the correct
      categorization of 82% of trees based on factors from 5- to 20-year intervals, and
      73% of trees using only resin duct counts from the most recent 5 years. We
      conclude that resin duct characteristics can be used to assess tree resistance to
      bark beetles across pine species, and offer a metric for management to enhance
      pest resistance.

PMID- 24305864
TI  - Life history affects how species experience succession in pen shell
      metacommunities.
AB  - In nature, very few species are common and broadly distributed. Most species are
      rare and occupy few sites; this pattern is ubiquitous across habitats and taxa.
      In spatially structured communities (metacommunities), regional distribution and
      local abundance may change as the relative effects of within-habitat processes
      (e.g., species interactions) and among-habitat processes (e.g., dispersal) may
      vary through succession. A field experiment with the marine benthic inhabitants
      of pen shells (Atrina rigida) tested how common and rare species respond to
      succession and metacommunity size. I followed community development through time
      and partitioned species into sessile and motile based on their natural history.
      Rare species drive diversity patterns and are influenced by metacommunity size:
      there are strong abundance-distribution differences between common and rare
      species in large metacommunities, but motile species show lower rates of change
      than sessile species. In small metacommunities both common and rare species have
      similar changes through time; the dichotomous distinction of common and rare
      species is not present. Edge effects in metacommunities affect species' changes
      in distribution and abundance. In large metacommunities diversity is higher in
      edge habitats relative to small metacommunities during early succession. However,
      edge effects benefit motile species over time in small metacommunities showing a
      rapid increase in diversity. Individual mobility is sensitive to regional
      community size and allows individuals to sort among different communities. In
      contrast, sessile species do not show this edge effect. Metacommunity theory is a
      useful framework for understanding spatially structured communities, but the
      natural history of coexisting species cannot be ignored. 

PMID- 24305865
TI  - Adolescents' reports of physical violence by peers in residential care settings:
      an ecological examination.
AB  - Physical victimization by peers was examined among 1,324 Jewish and Arab
      adolescents, aged 11 to 19, residing in 32 residential care settings (RCS) for
      children at-risk in Israel. Hierarchical Linear Modeling (HLM) was used to
      examine the relationships between physical victimization and adolescents'
      characteristics (age, gender, self-efficacy, adjustment difficulties,
      maltreatment by staff, and perceived social climate) as well as institution-level
      characteristics (care setting type, size, structure, and ethnic affiliation). For
      this study, we define physical violence as being grabbed, shoved, kicked,
      punched, hit with a hand, or hit with an object. Over 50% (56%) of the
      adolescents surveyed reported having experienced at least one form of physical
      violence by peers. Boys and younger adolescents were more likely to be victimized
      than girls and older adolescents. The results show that adolescents with
      adjustment difficulties or low social self-efficacy, and adolescents who perceive
      an institution's staff as strict and/or had experienced maltreatment by staff,
      are vulnerable groups for peer victimization. Lower levels of victimization were
      found in RCS with a familial element than in traditional group settings.
      Institutions with high concentrations of young people with adjustment
      difficulties and violent staff behaviors had higher levels of violence among
      residents. Applying an ecological perspective to an investigation of peer
      victimization in RCS enables the identification of risk factors at adolescent and
      institution levels. This type of examination has implications for child welfare
      practice and policy that can help in the development of prevention and
      intervention methods designed to tackle the involvement in violence of youth in
      care. 

PMID- 24305866
TI  - The interpersonal worlds of bullies: parents, peers, and partners.
AB  - Research has yet to examine the social influences of parents, peers, and partners
      on bullying. This study explored the impact of social relationships on bullies,
      victims, bully/victims, and uninvolved participants. A sample of 370 college-age
      participants was asked about bullying, family environment, friends' illegal
      behavior, and conflict resolution tactics in romantic relationships. Results
      indicated controls came from more secure and engaged families. Bully/victims
      reported friends engaging in more illegal behaviors than victims and uninvolved
      participants. Bullies and bully/victims reported more psychological coercion from
      their romantic partner. A logistic regression revealed peer illegal behaviors,
      psychological aggression, physical assault, and sexual coercion in romantic
      relationships best predicted bullies from non-bullies (67.3%). Based on these
      results, the interpersonal world of those involved with bullying significantly
      impacts behaviors. 

PMID- 24305867
TI  - Chirality effects on proline-substituted serine octamers revealed by infrared
      photodissociation spectroscopy.
AB  - Chiral preferences exist in proline-substituted serine octamers. For ions of [L
      Ser6 + Pro2]H(+), the stability preference is [L-Ser6 + L-Pro2]H(+) > [L-Ser6 + D
      Pro2]H(+) > [L-Ser6 + L-Pro1 + D-Pro1]H(+). Infrared photodissociation (IRPD)
      experiments were performed for the observed proline-substituted octamer ions in
      the range from 2700 to 3750 cm(-1). Chiral differentiation was achieved using the
      IRPD method, and the progressive changes in IRPD spectra due to the substitution
      were also reflected.

PMID- 24305868
TI  - The effect of supplementing zilpaterol hydrochloride on feeding performance and
      carcass characteristics of steers sorted by leptin genotype.
AB  - The focus of this investigation was to identify interactions that may exist among
      alleles of the leptin gene and supplementation of zilpaterol hydrochloride (ZH).
      Steers (n = 4,246; initial BW = 389.8 +/- 8.8 kg) were genotyped and sorted into
      1 of 3 leptin genotype (LG) groups (homozygous normal [CC], heterozygous [CT], or
      homozygous mutant ) from a candidate pool of 7,506 steers. Steers were allocated
      into 48 pens of which one-half were fed the beta-adrenergic agonist ZH and the
      balance, a control diet. During the pretreatment period (d 1 to 102), cattle of
      the TT genotype exhibited increased (P = 0.02) DMI compared to other genotypes
      and lower G:F than the CC genotype (P = 0.03). Cattle of the CT genotype had
      lower (P = 0.02) ADG compared to other genotypes for the treatment period. Cattle
      fed ZH had improved (P < 0.01) ADG and G:F compared to cattle on the control diet
      for both the treatment and entire study periods (d 1 to 125). For the entire
      study period, cattle of the TT genotype had greater (P = 0.03) DMI than the CT
      allele, with CT cattle having the lowest (P < 0.01) ADG and CC cattle having
      greatest (P < 0.01) G:F of all alleles. Cattle of the TT genotype had greater (P
      = 0.03) final shrunk weight than the CT allele. Cattle of the TT genotype had
      lower (P = 0.04) dressed yield compared to CT cattle and greater (P = 0.01)
      marbling score compared to CC cattle, with a concurrent increase (P < 0.01) in
      calculated empty body fat (EBF) over all alleles. Cattle fed ZH had greater (P <
      0.01) final shrunk weight, HCW, dressed yield, and LM area coupled with reduced
      (P < 0.01) marbling score, s.c. fat depth, EBF, and calculated USDA yield grade
      compared to control steers. Carcasses of the TT allele had a greater (P = 0.01)
      proportion of Choice carcasses than CT or CC alleles and lesser (P = 0.03)
      proportion of Select carcasses than CC alleles. Additionally, ZH supplemented
      cattle had fewer (P < 0.01) carcasses grading Premium Choice or better, Choice,
      and yield grade 3, 4, and 5 with subsequently more (P < 0.01) carcasses grading
      Select, Standard, and yield grade 1. Differences in live and carcass performance
      exist among leptin alleles, which may allow for sorting and improved timeliness
      of fed beef marketing. 

PMID- 24305869
TI  - Epigenetic DNA methylation in the promoters of peroxisome proliferator-activated
      receptor gamma in chicken lines divergently selected for fatness.
AB  - Peroxisome proliferator-activated receptor gamma is a master regulator of
      adipocyte differentiation and function. Expression of PPARgamma in mammals is
      regulated by DNA methylation; however, it is currently unknown whether chicken
      PPARgamma expression is regulated by DNA methylation. To enhance our
      understanding of molecular mechanisms underlying chicken adipose tissue
      development and adipogenesis, we investigated the promoter methylation status and
      gene expression of PPARgamma gene in Northeast Agricultural University broiler
      lines divergently selected for abdominal fat content (NEAUHLF). Deoxyribonucleic
      acid methylation was analyzed by bisulfite sequencing method, and mRNA expression
      was detected by real-time quantitative real time reverse-transcription polymerase
      chain reaction (RT-PCR). The analyzed region located from -1,175 to -301 bp
      upstream of the translation start codon ATG contains 6 CpG dinucleotides, which
      are located at positions -1,014, -796, -625, -548, -435, and -383 bp,
      respectively. The results revealed that the 3 CpGs at positions -548, -435, and 
      383 bp showed differential methylation between the lean and fat chicken lines,
      but the other 3 CpG sites at positions -1,014, -796, and -625 bp did not.
      PPARgamma gene promoter methylation in both chicken lines decreased with age, and
      PPARgamma promoter methylation levels were significantly higher in lean than fat
      broilers at 2 wk of age (79.9 to 64.5%; P < 0.0001), at 3 wk of age (66.7 to
      58.3%; P < 0.0001), and at 7 wk of age (50.0 to 42.7%; P = 0.0004). Real-time
      quantitative RT-PCR analysis showed that, negatively correlated with DNA
      methylation (Pearson's r = -0.653, P = 0.0057), PPARgamma expression was
      increased with age and significantly lower in lean than fat chicken lines at 2,
      3, and 7 wk of age (P < 0.0001). In conclusion, our findings suggest that chicken
      PPARgamma is regulated by DNA methylation during adipose tissue development. 

PMID- 24305870
TI  - Practical applications of trace minerals for dairy cattle.
AB  - Trace minerals have critical roles in the key interrelated systems of immune
      function, oxidative metabolism, and energy metabolism in ruminants. To date, the
      primary trace elements of interest in diets for dairy cattle have included Zn,
      Cu, Mn, and Se although data also support potentially important roles of Cr, Co,
      and Fe in diets. Trace minerals such as Zn, Cu, Mn, and Se are essential with
      classically defined roles as components of key antioxidant enzymes and proteins.
      Available evidence indicates that these trace minerals can modulate aspects of
      oxidative metabolism and immune function in dairy cattle, particularly during the
      transition period and early lactation. Chromium has been shown to influence both
      immune function and energy metabolism of cattle; dairy cows fed Cr during the
      transition period and early lactation have evidence of improved immune function,
      increased milk production, and decreased cytological endometritis. Factors that
      complicate trace mineral nutrition at the farm level include the existence of a
      large number of antagonisms affecting bioavailability of individual trace
      minerals and uncertainty in terms of requirements under all physiological and
      management conditions; therefore, determining the optimum level and source of
      trace minerals under each specific situation continues to be a challenge. Typical
      factorial approaches to determine requirements for dairy cattle do not account
      for nuances in biological function observed with supplementation with various
      forms and amounts of trace minerals. Trace mineral nutrition modulates
      production, health, and reproduction in cattle although both formal meta-analysis
      and informal survey of the literature reveal substantial heterogeneity of
      response in these outcome variables. The industry has largely moved away from
      oxide-based programs toward sulfate-based programs; however, some evidence favors
      shifting supplementation strategies further toward more bioavailable forms of
      inorganic and organic trace minerals. Furthermore, opportunities for specific
      modulation of aspects of health, milk production, and reproduction through
      supplementation strategies for diets of transition dairy cows are attractive
      because of the known dynamics of energy metabolism, immune function, and
      oxidative metabolism during this timeframe. 

PMID- 24305871
TI  - Application of fecal near-infrared spectroscopy and nutritional balance software
      to monitor diet quality and body condition in beef cows grazing Arizona
      rangeland.
AB  - Monitoring the nutritional status of range cows is difficult. Near-infrared
      spectroscopy (NIRS) of feces has been used to predict diet quality in cattle.
      When fecal NIRS is coupled with decision support software such as the Nutritional
      Balance Analyzer (NUTBAL PRO), nutritional status and animal performance can be
      monitored. Approximately 120 Hereford and 90 CGC composite (50% Red Angus, 25%
      Tarentaise, and 25% Charolais) cows grazing in a single herd were used in a study
      to determine the ability of fecal NIRS and NutbalPro to project BCS (1 = thin and
      9 = fat) under commercial scale rangeland conditions in central Arizona. Cattle
      were rotated across the 31,000 ha allotment at 10 to 20 d intervals. Cattle BCS
      and fecal samples (approximately 500 g) composited from 5 to 10 cows were
      collected in the pasture approximately monthly at the midpoint of each grazing
      period. Samples were frozen and later analyzed by NIRS for prediction of diet
      crude protein (CP) and digestible organic matter (DOM). Along with fecal NIRS
      predicted diet quality, animal breed type, reproductive status, and environmental
      conditions were input to the software for each fecal sampling and BCS date. Three
      different evaluations were performed. First, fecal NIRS and NutbalPro derived BCS
      was projected forward from each sampling as if it were a "one-time only"
      measurement. Second, BCS was derived from the average predicted weight change
      between 2 sampling dates for a given period. Third, inputs to the model were
      adjusted to better represent local animals and conditions. Fecal NIRS predicted
      diet quality varied from a minimum of approximately 5% CP and 57% DOM in winter
      to a maximum of approximately 11% CP and 60% DOM in summer. Diet quality
      correlated with observed seasonal changes and precipitation events. In evaluation
      1, differences in observed versus projected BCS were not different (P > 0.1)
      between breed types but these values ranged from 0.1 to 1.1 BCS in Herefords and
      0.0 to 0.9 in CGC. In evaluation 2, differences in observed versus projected BCS
      were not different (P > 0.1) between breed types but these values ranged from
      0.00 to 0.46 in Hereford and 0.00 to 0.67 in CGC. In evaluation 3, the range of
      differences between observed and projected BCS was 0.04 to 0.28. The greatest
      difference in projected versus observed BCS occurred during periods of lowest
      diet quality. Body condition was predicted accurately enough to be useful in
      monitoring the nutrition of range beef cows under the conditions of this study. 

PMID- 24305872
TI  - The effects of live yeast Saccharomyces cerevisiae on postweaning diarrhea,
      immune response, and growth performance in weaned piglets.
AB  - The effects of live yeast Saccharomyces cerevisiae (strain CNCM I-4407, 10(10)
      cfu/g; Actisaf; Lesaffre Feed Additives, Marcq-en-Baroeul, France) on the
      severity of diarrhea, immune response, and growth performance in weaned piglets
      orally challenged with enterotoxigenic Escherichia coli (ETEC) strain O149:K88
      were investigated. Live yeast was fed to sows and their piglets in the late
      gestation, suckling, and postweaning periods. Sows were fed a basal diet without
      (Control; n = 2) or with (Supplemented; n = 2) 1 g/kg of live yeast from d 94 of
      gestation and during lactation until weaning of the piglets (d 28). Suckling
      piglets of the supplemented sows were orally treated with 1 g of live yeast in
      porridge carrier 3 times a week until weaning. Weaned piglets were fed a basal
      starter diet without (Control; n = 19) or with (Supplemented; n = 15) 5 g of live
      yeast/kg feed for 2 wk. Significantly lower daily diarrhea scores (P < 0.05),
      duration of diarrhea (P < 0.01), and shedding of pathogenic ETEC bacteria (P <
      0.05) in feces was detected in the supplemented piglets. Administration of live
      yeast significantly increased (P < 0.05) IgA levels in the serum of piglets.
      Evidence indicates that decreased infection-related stress and severity of
      diarrhea in yeast-fed weaned piglets positively affected their growth capacity in
      the postweaning period (P < 0.05). The results suggest that dietary
      supplementation with live yeast S. cerevisiae to sows and piglets in the late
      gestation, suckling, and postweaning periods can be useful in the reduction of
      the duration and severity of postweaning diarrhea caused by ETEC. 

PMID- 24305873
TI  - Effects of excessive energy intake and supplementation with chromium propionate
      on insulin resistance parameters in nonlactating dairy cows.
AB  - The objective was to compare insulin resistance parameters in cows with adequate
      or excessive energy intake as well as in cows with excessive energy intake
      receiving Cr supplementation as chromium propionate. Thirteen multiparous,
      nonlactating Gir * Holstein cows were ranked by BW and BCS and assigned to 1 of 3
      dietary treatments on d 0: 1) diet to meet their ME requirements without Cr
      supplementation (MAN; n = 4), 2) diet to exceed their ME requirements without Cr
      supplementation (HIGH; n = 4), and 3) HIGH with 2.5 g/d of chromium propionate
      (HIGHCR; n = 5, with 10 mg of Cr/cow daily). Diets were formulated to provide
      100% of daily ME requirements of MAN and 177% of daily ME requirements of HIGH
      and HIGHCR cows and offered twice daily via individual self-locking head gates
      from d 0 to 88. Cow BW and BCS were recorded on d 0 and 88 of the experiment.
      Blood samples were collected before and 2 h after the morning feeding twice
      weekly. Preprandial revised quantitative insulin sensitivity check index
      (RQUICKI) was determined using serum glucose, insulin, and NEFA concentrations
      obtained before feeding. Glucose tolerance tests (GTT) were performed on d 32 and
      88 by infusing cows with 0.5 g of glucose/kg of BW whereas blood samples were
      collected at -15, 0, 10, 20, 30, 45, 60, and 90 min relative to infusion. Change
      in BCS tended to be greater in HIGH and HIGHCR (P = 0.09) compared with MAN cows.
      Within samples collected twice weekly, serum concentrations of glucose, insulin
      (beginning on d 14 of the experiment), and NEFA (preprandial samples only) were
      greater (P <= 0.05) in HIGH compared with HIGHCR cows and tended to be greater in
      HIGH compared with MAN cows (P <= 0.10) but did not differ (P >= 0.52) between
      HIGHCR and MAN cows. Moreover, HIGH cows had reduced RQUICKI compared with MAN (P
      = 0.02) and HIGHCR cows (P = 0.05) whereas RQUICKI was similar between MAN and
      HIGHCR cows (P = 0.53). Within samples collected during the GTT, mean serum
      insulin concentrations and insulin:glucose ratio were greater (P < 0.01) in HIGH
      compared with HIGHCR cows, tended (P <= 0.09) to be greater in HIGH compared with
      MAN cows, and were similar (P >= 0.16) between HIGHCR and MAN cows. Serum glucose
      concentrations were greater (P < 0.01) for HIGH compared with MAN and HIGHCR cows
      20 min relative to infusion. In conclusion, chromium propionate supplementation
      prevented the increase in insulin resistance caused by excessive energy intake in
      nonlactating dairy cows.

PMID- 24305874
TI  - Retention of n-3 polyunsaturated fatty acids in trimmed loin and belly is
      independent of timing of feeding ground flaxseed to growing-finishing female
      pigs.
AB  - A serial slaughter study, involving 45 individually housed Yorkshire female pigs,
      was conducted to evaluate the impact of feeding diets containing ground flaxseed
      (FS) during either the grower or late finisher phase on the incorporation of
      alpha-linolenic acid (18:3n-3) and n-3 highly unsaturated fatty acid metabolites
      (n-3 HUFA; all n-3 PUFA excluding 18:3n-3) in trimmed loin (longissimus dorsi)
      and belly (cross-section cut). Growth performance, carcass characteristics, and
      pork quality were also monitored. The three feeding regimens were 1) feeding a
      diet containing 10% FS between 25 and 50 kg BW, followed by FS-free diets (low n
      3 PUFA content) until 110 kg BW (FS early, FSE; n = 16), 2) feeding no FS diets
      between 25 and 85 kg BW, followed by a diet containing 6% FS until 110 kg BW (FS
      late, FSL; n = 17), and 3) feeding FS-free diets between 25 and 110 kg BW (CON; n
      = 8). Pigs were assigned to 1 of 3 target slaughter weights for determining whole
      nutrient retention: 50 kg (n = 4 and 5 for FSE and FSL, respectively), 85 kg (n =
      4 for FSE and FSL), and 110 kg (n = 8 pigs for FSE, FSL, and CON). An additional
      4 pigs were slaughtered to determine initial body composition at 25 kg BW. Pigs
      on treatments FSE and FSL consumed equal cumulative amounts of FS (5.1 vs. 5.2
      kg). Fatty acid content was expressed as milligrams per 100 g of fresh tissue. No
      treatment effect was observed for growth performance, body composition, carcass
      characteristics, loin meat quality, and fat content in the loin and belly
      samples. In the loin, the content of 18:3n-3 at 110 kg BW was greater for FSL
      than FSE and CON (P < 0.01; 143, 76.4, and 37 mg/100 g, respectively), whereas
      the contents of 18:3n-3 in the belly were greater for both FSL and FSE than CON
      (752, 667, and 207 mg/100 g for FSL, FSE, and CON, respectively). Within tissues,
      the content of n-3 HUFA was similar for FSL and FSE, and both were greater (P <
      0.01) than CON for loin (41.7, 30.3, and 17.9 mg/100 g, respectively) and belly
      (168, 179, and 71.2 mg/100 g, respectively), except for docosahexaenoic acid
      (22:6n-3) in the loin. Feeding FS tended to reduce the content of arachidonic
      acid (20:4n-6) and adrenic acid (22:4n-6; P < 0.10) in the loin and belly. In the
      belly but not in the loin, feeding FS reduced the content of total SFA (P = 0.05)
      and tended to reduce the content of the sum of MUFA (P = 0.09). Within the loin
      and belly, the ratio of n-6 to n-3 PUFA and the content of n-3 HUFA were similar
      for FSE and FSL, with the exception of 18:3n-3 and 20:4n-6 in the loin, for which
      contents were greater for FSL than FSE (P < 0.05). These results indicate that
      providing modest amounts of FS leads to a substantial enrichment of 18:3n-3 and n
      3 HUFA in pork products. The enrichment of n-3 HUFA appears to be independent of
      timing of feeding FS, providing flexibility as to when n-3 PUFA can be fed to
      generate n-3 PUFA-enriched pork products. 

PMID- 24305875
TI  - Reprogramming hMSCs morphology with silicon/porous silicon geometric micro
      patterns.
AB  - Geometric micro-patterned surfaces of silicon combined with porous silicon
      (Si/PSi) have been manufactured to study the behaviour of human Mesenchymal Stem
      Cells (hMSCs). These micro-patterns consist of regular silicon hexagons
      surrounded by spaced columns of silicon equilateral triangles separated by PSi.
      The results show that, at an early culture stage, the hMSCs resemble quiescent
      cells on the central hexagons with centered nuclei and actin/beta-catenin and a
      microtubules network denoting cell adhesion. After 2 days, hMSCs adapted their
      morphology and cytoskeleton proteins from cell-cell dominant interactions at the
      center of the hexagonal surface. This was followed by an intermediate zone with
      some external actin fibres/beta-catenin interactions and an outer zone where the
      dominant interactions are cell-silicon. Cells move into silicon columns to
      divide, migrate and communicate. Furthermore, results show that Runx2 and vitamin
      D receptors, both specific transcription factors for skeleton-derived cells, are
      expressed in cells grown on micropatterned silicon under all observed
      circumstances. On the other hand, non-phenotypic alterations are under cell
      growth and migration on Si/PSi substrates. The former consideration strongly
      supports the use of micro-patterned silicon surfaces to address pending questions
      about the mechanisms of human bone biogenesis/pathogenesis and the study of bone
      scaffolds. 

PMID- 24305876
TI  - FGFR1-WNT-TGF-beta signaling in prostate cancer mouse models recapitulates human
      reactive stroma.
AB  - The reactive stroma surrounding tumor lesions performs critical roles ranging
      from supporting tumor cell proliferation to inducing tumorigenesis and
      metastasis. Therefore, it is critical to understand the cellular components and
      signaling control mechanisms that underlie the etiology of reactive stroma.
      Previous studies have individually implicated fibroblast growth factor receptor 1
      (FGFR1) and canonical WNT/beta-catenin signaling in prostate cancer progression
      and the initiation and maintenance of a reactive stroma; however, both pathways
      are frequently found to be coactivated in cancer tissue. Using autochthonous
      transgenic mouse models for inducible FGFR1 (JOCK1) and prostate-specific and
      ubiquitously expressed inducible beta-catenin (Pro-Cat and Ubi-Cat, respectively)
      and bigenic crosses between these lines (Pro-Cat * JOCK1 and Ubi-Cat * JOCK1), we
      describe WNT-induced synergistic acceleration of FGFR1-driven adenocarcinoma,
      associated with a pronounced fibroblastic reactive stroma activation surrounding
      prostatic intraepithelial neoplasia (mPIN) lesions found both in in situ and
      reconstitution assays. Both mouse and human reactive stroma exhibited increased
      transforming growth factor-beta (TGF-beta) signaling adjacent to pathologic
      lesions likely contributing to invasion. Furthermore, elevated stromal TGF-beta
      signaling was associated with higher Gleason scores in archived human biopsies,
      mirroring murine patterns. Our findings establish the importance of the FGFR1-WNT
      TGF-beta signaling axes as driving forces behind reactive stroma in aggressive
      prostate adenocarcinomas, deepening their relevance as therapeutic targets.

PMID- 24305877
TI  - CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by
      regulating ZEB1 expression.
AB  - The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its
      contributions to progression and metastasis have not been evaluated. Here, we
      show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and
      colorectal tumors in which its expression level correlates positively with
      distant metastasis. CUL4A overexpression in normal or malignant human mammary
      epithelial cells increased their neoplastic properties in vitro and in vivo,
      markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic
      capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast
      cancer cells inhibited these processes. Mechanistically, we found that CUL4A
      modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a
      manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven
      proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast
      cancers, ZEB1 expression correlated positively with CUL4A expression and distant
      metastasis. Taken together, our findings reveal a pivotal role of CUL4A in
      regulating the metastatic behavior of breast cancer cells.

PMID- 24305880
TI  - Editors' note.

PMID- 24305878
TI  - Dramatic antitumor effects of the dual MET/RON small-molecule inhibitor LY2801653
      in non-small cell lung cancer.
AB  - Lung cancer is a heterogeneous disease encompassing a wide array of genetic
      abnormalities. The MET receptor tyrosine kinase is altered in many lung cancers,
      especially non-small cell lung cancer (NSCLC), and clinical trials of MET
      inhibitors that are under way are documenting cases of acquired resistance. On
      the basis of the evidence that the RON tyrosine kinase receptor can also be
      overexpressed in NSCLC, we evaluated the potent MET/RON dual kinase inhibitor
      LY2801653 in this setting. LY2801653 was more efficacious than the
      MET/ALK/RON/ROS inhibitor crizotinib with a distinct pattern of downstream
      signaling effects. Using the PamGene platform, we found that inhibition of MET
      and RON was associated with decreased phosphorylation of CBL, PI3K, and STAT3. In
      classic and orthotopic mouse xenograft models of lung cancer, LY2801653 decreased
      tumor growth, dramatically inhibiting mitotic events and angiogenesis. Taken
      together, our results argued that specific targeting of the MET/RON kinases could
      provide robust inhibition of cell proliferation and tumor outgrowth in multiple
      in vitro and in vivo models of NSCLC. These findings offer a robust preclinical
      proof of concept for MET/RON targeting by LY2801653 as a promising small-molecule
      modality to treat NSCLC.

PMID- 24305879
TI  - MDR1 synonymous polymorphisms alter transporter specificity and protein stability
      in a stable epithelial monolayer.
AB  - The drug efflux function of P-glycoprotein (P-gp) encoded by MDR1 can be
      influenced by genetic polymorphisms, including two synonymous changes in the
      coding region of MDR1. Here we report that the conformation of P-gp and its drug
      efflux activity can be altered by synonymous polymorphisms in stable epithelial
      monolayers expressing P-gp. Several cell lines with similar MDR1 DNA copy number
      were developed and termed LLC-MDR1-WT (expresses wild-type P-gp), LLC-MDR1-3H
      (expresses common haplotype P-gp), and LLC-MDR1-3HA (a mutant that carries a
      different valine codon in position 3435). These cell lines express similar levels
      of recombinant mRNA and protein. P-gp in each case is localized on the apical
      surface of polarized cells. However, the haplotype and its mutant P-gps fold
      differently from the wild-type, as determined by UIC2 antibody shift assays and
      limited proteolysis assays. Surface biotinylation experiments suggest that the
      non-wild-type P-gps have longer recycling times. Drug transport assays show that
      wild-type and haplotype P-gp respond differently to P-gp inhibitors that block
      efflux of rhodamine 123 or mitoxantrone. In addition, cytotoxicity assays show
      that the LLC-MDR1-3H cells are more resistant to mitoxantrone than the LLC-MDR1
      WT cells after being treated with a P-gp inhibitor. Expression of polymorphic P
      gp, however, does not affect the host cell's morphology, growth rate, or
      monolayer formation. Also, ATPase activity assays indicate that neither basal nor
      drug-stimulated ATPase activities are affected in the variant P-gps. Taken
      together, our findings indicate that "silent" polymorphisms significantly change
      P-gp function, which would be expected to affect interindividual drug disposition
      and response.

PMID- 24305881
TI  - Foreword.

PMID- 24305882
TI  - Nematode reproductive and ingestive responses to helminth and host chemical
      stimuli.
AB  - Current knowledge of the involvement of chemical stimuli in the reproductive and
      ingestive physiology of zooparasitic nematodes is reviewed. The habitat of
      zooparasitic nematodes, coupled with their sensory reduction, indicates that
      chemical stimuli may modulate most aspects of their behavioral physiology.
      Nematodes respond to the feeding status of the host so that the helminth's
      pharyngeal pumping, site selection, and sexual activity may be altered. Biogenic
      amines from the host, such as histamine, dopamine, or serotonin, may synchronize
      host and helminth ingestion. Octopamine, which is released by nematodes,
      depresses ingestion by male, but not female, worms. Biogenic amines may also
      regulate ovipositioning by female helminths. Nematodes release pheromones that
      enable precopulatory location of a mate. The male helminth is activated by both
      components of the female's pheromone while movement by the female is probably
      arrested by male-produced chemicals. Continuation of spectral analyses may allow
      future identification of female pheromone. The male's pheromone receptor binds
      lectin that is specific for mannose residues. Host immunity also alters the
      behavior of nematodes. Ingestion by nematodes is depressed by serum, particularly
      IgG1, from infected animals. Similar results occur after immunization of
      noninfected hosts. Immune serum has no effect on pheromone communication between
      the sexes of helminth, but depresses ovipositional behavior of female worms.
      Exploitation of these chemical signals and the helminths' responses may allow
      novel techniques for disease control. 

PMID- 24305883
TI  - Role of chemical substances from fish hosts in hatching and host-finding in
      monogeneans.
AB  - Hatching responses to chemical stimuli appear to have evolved independently in
      different kinds of monogenean skin and gill parasites of fishes, particularly in
      those parasites associated with bottom-dwelling hosts. Some monogeneans, such
      asEntobdella soleae, have two hatching strategies, responding readily to host
      skin mucus but hatching spontaneously in small numbers in the absence of the
      host. Other monogeneans, such asAcanthocotyle lobianchi, have abandoned
      spontaneous hatching and rely entirely on a "sit- and-wait" strategy, but
      improvements in the speed of hatching provide opportunities to take advantage of
      brief periods of contact between the eggs and the host. This has led to the loss
      of ciliated epidermal cells and to the inability to swim. Comparison of the eggs
      and hatching responses of two unrelated monogeneans,Leptocotyle minor
      andHexabothrium appendiculatum, which share the same dogfish host, reveals
      evidence of convergence. Small, stable molecules such as urea, excreted by the
      host, have been implicated as hatching stimulants in monogeneans. There is
      evidence that host recognition inE. soleae is by chemoperception but, in contrast
      with the lack of specificity of the chemical hatching stimuli, this appears to be
      of a specific nature. 

PMID- 24305884
TI  - Chemical communication in hermaphroditic digenetic trematodes.
AB  - Adult hermaphroditic digenetic trematodes show a tendency to pair or aggregate in
      vivo, on the chick chorioallantois, and in vitro. Intraspecific pairing studies
      onEchinostoma revolutum, Leucochloridiomorpha constantiae, andAmblosoma suwaense
      are reviewed. Lipophilic excretory-secretory products are involved in chemical
      communication in hermaphroditic digeneans. Free sterols are involved in chemical
      attraction inL. constantiae andE. revolutum and sterol esters play a similar role
      inA. suwaense. In vitro pairing betweenE. revolutum and various other digenean
      species suggest that interspecific pairing occurs in Digenea and that nonspecific
      factors are involved. 

PMID- 24305885
TI  - Internal chemical communication within flatworms.
AB  - An understanding of reproductive function is important for control of parasitic
      helminths. In cestodes and trematodes virtually nothing is known about regulatory
      and coordinating mechanisms that control maturation, gamete formation, egg
      production, and related processes. Neurosecretory neurons have been reported in
      various species but specific modes of action of neurohormones have yet to be
      demonstrated. The role of ecdysone is being investigated. 

PMID- 24305886
TI  - Schistosome behavior in vitro.
AB  - Schistosome adults attract each other in vitro and the attraction is chemically
      mediated. InSchistosoma mansoni adults, excretory-secretory (ES) products of
      worms of one sex attract worms of the opposite sex, and at least the lipophilic
      fraction is attractive. Intra- and interspecific attraction occurs inSchistosoma
      mansoni, S. japonicum, andS. haematobium adults. Current knowledge of schistosome
      behavior in vitro is reviewed. 

PMID- 24305887
TI  - Chemical communication in adult schistosomes.
AB  - Lipids released bySchistosoma mansoni adult males attract females in vitro. Lipid
      release is modulated by the presence of other worms. AlthoughS. mansoni males
      release lipid when paired with females, the release is enhanced when they are
      separated.S. japonicum adults release more free sterols when incubated
      individually than when incubated together. Similarly, individually incubatedS.
      haematobium males release more free sterols than when incubated in groups.
      However,S. haematobium females incubated in groups release more free fatty acids
      than do equal numbers of males or pairs incubated in groups. There is evidence
      thatS. mansoni adult females concomitantly accumulate and release cholesterol in
      the absence of an exogenous supply, although de novo synthesis of cholesterol in
      schistosomes has not yet been demonstrated. Schistosomula and adult schistosomes
      incorporate exogenous lipids. Lipids are incorporated chiefly through the
      tegument. Cholesterol is transferred between males and females. 

PMID- 24305888
TI  - Mating preference inSchistosoma mansoni.
AB  - We investigated the suitability of an in vitro culture system for measurement of
      mating behavior ofSchistosoma mansoni. The criteria used to evaluate this system
      were the level of phosphorylated nucleotides, egg production, and mating status
      of parasites. The level of ATP, ADP, AMP, and G6-P was measured at different time
      intervals during cultivation of worm pairs and remained essentially the same as
      that of control worms for up to 6 days. Egg production was observed in this
      system during 19 days of cultivation. Peak egg production occurred on day 4 with
      72% of the total eggs being laid during the first week of cultivation. The
      variability in the number of eggs produced by different pairs ofS. mansoni
      necessitated the selection and matching of tubes with the same number of eggs
      after 48 hr. This permitted the detection of small changes in egg production by
      decreasing intertube variation. Mating recognition between male and femaleS.
      mansoni was evaluated by culturing separated adult worms with their original
      partner or with a different partner. During the first 24 hr, mating occurred
      among a greater percentage of worm pairs comprised of their original partner than
      among worm pairs comprised of different partners (P < 0.001). After 48 and 72 hr
      of cultivation, these differences were not statistically significant. Similar
      results were obtained with a culture of mixed males and females. Two drugs were
      studied for their effects on the mating ofS. mansoni in vitro. Aminoglutethimide
      (AG) at a concentration of 1 * 10(-4) had no effect on the frequency of mating
      whereas diethyldithiocarbamate (DDC) completely inhibited mating at a
      concentration of 3 * 10(-6) M and reduced the level of ATP in these worms. 

PMID- 24305889
TI  - Extraction of intersexual chemoattractants fromSchistosoma mansoni.
AB  - FemaleSchistosoma mansoni and their excretory-secretory (ES) products were
      extracted with a series of solvents to provide fractions of varying polarity.
      These fractions were assayed for chemoattractivity to males in vitro. One major
      component of these mixtures was found to be nonattractive and was identified as
      cholesterol.n-Pentane- and ether-soluble fractions derived from ES products
      exhibited chemoattractive activity comparable to that possessed by whole-worm
      extracts, but appeared to be simpler mixtures. 

PMID- 24305890
TI  - In vitro orientation of maleSchistosoma mansoni to extracts derived from female
      schistosomes.
AB  - Chemical orientation of adult maleSchistosoma mansoni was studied during
      cultivation in vitro. Directional preference was assessed in culture vessels
      marked with compass coordinates by the application of circular statistics for
      determining clustering and orientation to a predicted direction. Organic solvent
      extracts of fresh female schistosomes and supernatant fluids from 72-hr cultures
      of female parasites were tested for potential chemotactic activity. Analysis
      showed significant (P < 0.05) directional preference and clustering of male worms
      towards test compounds at all time periods (24, 48, and 72 hr) with one mixture
      of female extracts and at one of three time periods with a second female extract.
      Male worms did not respond to ecdysone, cholesterol, or solvent controls by
      orienting in predicted direction, although clustering was observed on two of 12
      occasions. These results indicate the presence of a chemoattractant compound(s)
      in female extracts. 

PMID- 24305891
TI  - Time-lapse video tape documentation of chemical orientation bySchistosoma mansoni
      in vitro.
AB  - In vitro, the opposite sexes ofS. mansoni are attracted to each other by some
      means of premating communication which culminates in aggregation and copulation
      of sexual pairs within 24 hr. The system used for time-lapse video tape
      documentation of worm sexual behavior in vitro is described and evidence of
      sexual chemoattraction is presented. 

PMID- 24305892
TI  - Male-stimulated female maturation inSchistosoma: A review.
AB  - InSchistosoma mansoni and other schistosome species, pairing of the female with a
      male partner is necessary for the completion of reproductive morphogenesis and
      growth. Permanent contact with a male is also necessary for the maintenance of
      reproductivity in the sexually mature female. This phenomenon appears to be
      unique within the animal kingdom. The mechanism of male-stimulated female
      reproductive development in schistosomes remains unknown however. In this paper,
      the theories for the nature of the process are reviewed briefly, recent findings
      are added, and the biological and technical problems associated with its study
      are highlighted. 

PMID- 24305893
TI  - Structural and metabolic changes in femaleSchistosoma mansoni following male
      stimulation.
AB  - Pairing of males and females from single-sex infections results in the
      multiplication and differentiation of undifferentiated cells of the vitelline
      lobule culminating in the production of mature vitelline cells involved in egg
      shell formation. These changes are accompanied by increases in the rate of uptake
      of tyrosine, thymidine, and an increased accumulation of calcium. 

PMID- 24305894
TI  - Elemental changes during sexual maturation inSchistosoma mansoni.
AB  - Changes in the elemental composition ofSchistosoma mansoni in relation to age and
      sexual status are described, and studies on the structural localization of
      calcium in adult worms and the elemental composition of the tegument
      subtegumental tissues are reviewed. Some preliminary results on the distribution
      of Ca(2+)-dependent ATPase activity in the tegument of worms from both mixed and
      single-sex infections are also presented. 

PMID- 24305895
TI  - Influence of mating on surface nutrient exchange in schistosomes.
AB  - In schistosomes, the mating process influences male-female transfer and gender
      specific exchange of nutrients. The paired male schistosome provides glucose to
      the female partner. Male-to-female intertegumental transfer of(14)C-labeled
      glucose,(14)C-labeled 3-O-methylglucose, [(14)C]2-deoxyglucose and 2
      fluorodeoxyglucose has been demonstrated in schistosomes. This phenomenon has
      been studied extensively inSchistosoma mansoni, and confirmed inSchistosoma
      japonicum, as well asS. haematobium, using radioactive pulsing methods. Male
      schistosomes contain significantly greater quantities (nmol/mg worm water) of
      glucose than do females. The transfer of glucose is apparently not an energy
      dependent process, but occurs along this concentration gradient. Most, if not
      all, of the glucose utilized by the female is transferred from the male partner
      via tegumentary-facilitated diffusion mechanisms, free diffusion, or some
      combination of these two components. Unpaired male schistosomes contain greater
      quantities of glycogen than do comparable paired schistosomes, indicating that
      the presence of a female in the gynecophoral canal depletes the reserves of the
      male partner; this is additional indirect evidence for male-to-female transfer of
      glucose. Tegumentary surface uptake of acidic amino acids has been compared in
      paired and separated male and female schistosomes. InS. mansoni, a saturable
      carrier-mediated mechanism has been defined which operates only in unpaired male
      and unpaired female teguments. In contrast, the uptake of aspartate and glutamate
      is not seen in paired worms of this species. Tegumental uptake of acidic amino
      acids is not observed in paired or unpaired male or femaleS. japonicum. However,
      inS. haematobium, significant quantities of aspartate are taken up by both paired
      and unpaired male schistosomes. Measurable aspartate uptake is seen in paired
      femaleS. haematobium, but in the separated female, there is minimal uptake of
      this acidic amino acid. Thus the permeability of the teguments of human
      schistosome species to acidic amino acids is modified in response to the paired
      state inS. mansoni andS. haematobium, but these characteristics are not shared
      byS. japonicum. 

PMID- 24305896
TI  - Portal serum constituents possible determinants for anatomical localization
      ofSchistosoma mansoni during maturation and reproduction.
AB  - Coupled adult pairs ofSchistosoma mansoni were incubated in medium containing
      either peripheral or portal serum from rat, rabbit, hamster, or man, and egg
      production was measured daily. In all cases egg production was significantly
      increased for pairs in the presence of portal sera compared with that in the
      presence of peripheral sera. Fractionation of rabbit portal serum according to
      molecular weight demonstrated that the most active component(s) were in the range
      of 2000 to 50,000. Similarly, a rat portal serum fraction in the range of 2000 to
      30,000 molecular weight was most stimulatory. These fractions were as effective
      in stimulating oviposition as whole portal serum. CONCLUSIONS: (1) portal serum
      factor(s) exist that stimulateS. mansoni oviposition in vitro; (2) they are
      present in susceptible and nonsusceptible hosts; and (3) the molecular weight
      range for the active components is larger than would be expected for simple
      carbohydrates, amino acids, or free fatty acids absorbed from the
      gastrointestinal tract.

PMID- 24305897
TI  - Limitations to schistosome growth and maturation in nonpermissive hosts.
AB  - The life cycle of schistosomes is reviewed in its various steps, both in
      permissive hosts (in which the cycle is completed) and in nonpermissive hosts
      (which excrete no viable eggs as a result of the infection). A large worm loss
      occurs at (or after) the lung stage in both types of hosts ("normal attrition")
      and some nonpermissive hosts (like the rat) have an additional elimination of
      worms from the portal circulation. Worm growth and reproductive maturation are
      also impaired in several nonpermissive hosts and the possible host-parasite
      interactions leading to such limitations are discussed, with special reference to
      hormonal influences. Attention is also given to peculiar phenomena occurring in
      some hosts, like the late portal worm elimination in rhesus monkeys, the
      migration from mesenteric veins to lungs in rats, and the block to egg excretion
      in guinea pigs. The steps of the schistosome life cycle which appear vulnerable
      in several hosts are contrasted with the steps which are carried out successfully
      in the majority of hosts studied. 

PMID- 24305898
TI  - Identification of sex-linked antigens ofSchistosoma mansoni by
      immunoelectrophoresis and immunoblotting.
AB  - Immunoelectrophoresis and immunoblotting techniques, using sera from hyperimmune
      rabbits and infected mice, were used to analyze antigens ofSchistosoma mansoni. A
      comparison was made between the antigenic composition of adult male and female
      worms, isolated from monosexually and bisexually infected hamsters. A large
      number of female-specific and a few male-specific antigens were detected. The
      antigenic composition of females isolated from monosexually infected hamsters was
      shown to be very different from that of paired females. The presence of a major
      female-specific antigen with an apparent molecular weight of 32 kd in paired
      females only, suggests that synthesis of this antigen by female worms is
      initiated by the male partner. Analysis of the humoral immune response of mice
      receiving bisexual or monosexual infections showed that both mono- and bisexually
      infected mice develop a major humoral immune response to a 36-kd polypeptide
      antigen. A response to a major polypeptide antigen with an apparent molecular
      weight of 60 kd was observed in bisexually infected mice only. No antibodies
      reactive with this 60-kd polypeptide are formed during mon-osexual infections
      with either male or female worms. The 60-kd polypeptide was, however, present in
      monosexually reared females. This presence, and the presence in bisexually reared
      males, suggests a transfer of this antigen from females to males. 

PMID- 24305899
TI  - Biology of tegument associated IgG-Fc and C3 receptors inSchistosoma mansoni.
AB  - Mechanisms by which schistosomes escape host immune responses are reviewed, with
      particular emphasis regarding the possible contributions of host or host-like Fc
      and C3 receptors on adult parasites. 

PMID- 24305900
TI  - Strategies to determine the molecular basis of chemical communication by
      trematodes.
AB  - The identification of pheromones and chemicals that may inhibit or stimulate
      growth and reproduction necessarily leads to the consideration of biochemical
      methods to isolate and characterize these molecules. Analysis ofSchistosoma
      mansoni surface antigens by direct radioiodination, metabolic labeling with
      tritiated and(14)C-tagged hexose precursors, affinity chromatography, isoelectric
      focusing, hydrophobic chromatography, and competitive inhibition is presented to
      illustrate methods of immunochemical analysis and antigen purification. Technical
      problems that may arise when investigating parasite molecular biology are
      described. Evidence of diminished fecundity of female worms in acutely infected
      mice supports the theory of a "crowding effect" in murine schistosomiasis and
      suggests the possibility that worm secretions or metabolites may function as
      chemical messages to inhibit oviposition. There is also evidence that the immune
      response of mice to an isolated surface antigen from adult worms results in the
      attenuation of hepatic granulomata of challenge infections. Several hypotheses
      are proposed to elucidate the molecular basis for chemical communication between
      trematodes and analytical approaches to test these hypotheses are outlined. 

PMID- 24305901
TI  - Fundamental aspects and potential roles of ecdysteroids in schistosomes an update
      overview.
AB  - The human digenic trematodeSchistosoma mansoni produces ecdysteroid hormones.
      Both ecdysone (22R)-2beta,3beta,14,22,25-pentahydroxy-cholest-7-en-6-one and 20
      hydroxyecdysone (22R)-2beta,3beta, 14,20,22,25-hexahydroxycholest-7-en-6-one were
      detected during the critical development stages of this bisexual parasite: during
      the exponential growth phase to adult stage (day 11 postinfection) and during the
      sexual maturation of adult and egg laying (day 40 postinfection). The parasites
      released their ecdysteroid hormones in the biological fluids of the infected
      vertebrates as soon as six days postinfection. In addition, the time course of
      the ecdysteroid titer was correlated with the susceptibility or the innate
      resistance of the host to schistosome infection. Moreover, we demonstrated that
      after a schistomicide therapy, ecdysteroids from urine of infected children
      decreased markedly four days after drug administration. We also have demonstrated
      that immunization of rodents with an ecdysone-BSA complex led to the reduction of
      the worm burden. By in vitro studies, we have shown that the ecdysterone
      antibodies were able to kill the juvenile worms within 24 hr. In addition, we
      have demonstrated that the enzymes Superoxide dismutase (SOD, EC 1.15.1.1) were
      present in schistosomes and that the total Superoxide dismutase activities in
      both males and females could be correlated with the 20-hydroxyecdysone within
      parasites. 

PMID- 24305902
TI  - Developmental changes in energy metabolism ofSchistosoma mansoni and
      physiological role of oxygen in maintaining parasite function.
AB  - The time course of the conversion from a cyanide-sensitive to a cyanide
      insensitive energy metabolism in immatureSchistosoma mansoni was followed by
      correlating transitions in CO2 and lactate formation with physiological
      properties of the parasite. Volume conducted electrical potentials and
      measurement of CO2 evolution indicate that 3-hr posttransformational
      schistosomula are highly sensitive to 1 mM cyanide. By 24 hr after
      transformation, evolution of CO2 under control conditions is reduced by 77% from
      3-hr levels, while lactate excretion rises by 84%. At the 24-hr stage, neither
      cyanide nor rotenone affects the frequency or magnitude of endogenous electrical
      transients, but cyanide does eliminate 83 % of the already reduced levels of CO2
      evolved in 24-hr schistosomula. The adult parasite evolves a low level of CO2
      which is reduced by 88% in the presence of 1 mM cyanide. No significant Pasteur
      effect is detected, however, and endogenous electrical activity as well as
      mechanical responses of the adult musculature are unaffected by cyanide exposure.
      Furthermore, adult schistosomes were not adversely affected in terms of the
      physiological parameters measured by 24-hr incubations in oxygen-free medium.
      Adults were only marginally affected by 24-hr exposure to several respiratory
      inhibitors, but responded rapidly to some uncouplers of oxidative
      phosphorylation, including 2,4-DNP, carbonyl cyanide 3-chlorphenylhydrazone, and
      closantel. Our results indicate that schistosomula continue to rely on cyanide
      sensitive respiratory components for at least 3 hr after transformation; by 24
      hr, however, the parasites are metabolically similar to the adult stage, i.e,
      they depend on lactate fermentation for most of their energy requirements. 

PMID- 24305903
TI  - Effects of steroids and steroid synthesis inhibitors on fecundity ofSchistosoma
      mansoni in vitro.
AB  - In vitro egg production bySchistosoma mansoni was examined following a 72-hr
      incubation period in the presence of various steroids, steroid precursors, or
      steroid synthesis inhibitors. Mevinolin, an inhibitor of cholesterol
      biosynthesis, significantly decreased egg production at 10(-6) M. However,
      neither cholesterol (at 10(-5) M) nor any of its hydroxylated derivatives (at 10(
      4) M) affectedS. mansoni fecundity. Dianisidine, an inhibitor of cholesterol
      metabolism to hormonal products, was also ineffective in influencing egg
      production. The steroid hormones progesterone, 17alpha-hydroxyprogesterone and
      medroxyprogesterone acetate, all significantly decreased egg production; however,
      parasite muscle tension was also significantly reduced by the concentrations of
      these steroids needed to produce an effect on egg laying. Various androgenic
      hormones (androsterone, androstenedione, testosterone) and estrogenic hormones
      (17beta-estradiol and estrone) demonstrated no effect on in vitro egg production.
      Significant elevation in the rate of parasite oviposition was seen in the
      presence of the corticosteroid prednisolone (at 10(-5) M), but not by
      dexamethasone, a corticosteroid analog. 

PMID- 24305905
TI  - Evaluating the selection, training, and support of peer support workers in the
      United Kingdom.
AB  - This article describes the preparation, selection, training, and support of a
      group of people with lived experience of mental distress/illness and mental
      health service use to work as peer support workers (PSWs). The PSWs were
      recruited to provide support alongside conventional aftercare to service users
      discharged from acute psychiatric units in London, England. Training was
      delivered over 12 weekly, 1-day sessions from April to July 2010. Supervision and
      support were provided by a peer support coordinator and a training facilitator.
      The overall view of the training by those who went on to work as PSWs was that it
      was a valuable, challenging, yet positive experience that provided them with a
      good preparation for the role. A key area for improvement concerned the strength
      of emotional involvement and feelings PSWs had for their peers, especially in
      regard to ending the support relationship. Skilled, sensitive supervision and
      support is essential for the success of such roles.

PMID- 24305904
TI  - Simultaneous prediction of binding free energy and specificity for PDZ domain
      peptide interactions.
AB  - Interactions between protein domains and linear peptides underlie many biological
      processes. Among these interactions, the recognition of C-terminal peptides by
      PDZ domains is one of the most ubiquitous. In this work, we present a
      mathematical model for PDZ domain-peptide interactions capable of predicting both
      affinity and specificity of binding based on X-ray crystal structures and
      comparative modeling with ROSETTA. We developed our mathematical model using a
      large phage display dataset describing binding specificity for a wild type PDZ
      domain and 91 single mutants, as well as binding affinity data for a wild type
      PDZ domain binding to 28 different peptides. Structural refinement was carried
      out through several ROSETTA protocols, the most accurate of which included
      flexible peptide docking and several iterations of side chain repacking and
      backbone minimization. Our findings emphasize the importance of backbone
      flexibility and the energetic contributions of side chain-side chain hydrogen
      bonds in accurately predicting interactions. We also determined that predicting
      PDZ domain-peptide interactions became increasingly challenging as the length of
      the peptide increased in the N-terminal direction. In the training dataset,
      predicted binding energies correlated with those derived through calorimetry and
      specificity switches introduced through single mutations at interface positions
      were recapitulated. In independent tests, our best performing protocol was
      capable of predicting dissociation constants well within one order of magnitude
      of the experimental values and specificity profiles at the level of accuracy of
      previous studies. To our knowledge, this approach represents the first integrated
      protocol for predicting both affinity and specificity for PDZ domain-peptide
      interactions. 

PMID- 24305906
TI  - Adding SUGAR: service user and carer collaboration in mental health nursing
      research.
AB  - SUGAR (Service User and Carer Group Advising on Research) is an initiative
      established to develop collaborative working in mental health nursing research
      between mental health service users, carers, researchers, and practitioners at
      City University London, United Kingdom. This article will describe the background
      of SUGAR; how the group operates; some of the achievements to date, including
      researcher reflections; and case studies of how this collaboration influences our
      research. Written reflective narratives of service user and carer experiences of
      SUGAR were analyzed using constant comparative methods by the members. Common
      themes are presented with illustrative quotes. The article highlights the
      benefits and possible limitations identified to date by members of SUGAR,
      outlines future plans, and considers the findings in relation to literature on
      involvement and empowerment. This article, written by staff and members of SUGAR,
      is the first venture into collaborative writing of the group and reflects the
      shared ethos of collaborative working.

PMID- 24305907
TI  - Caring for dad at 100: challenges and coping strategies.
AB  - The author presents five exemplars of caregiving challenges taken from a 100-day
      diary she kept during her father's 100th year and then identifies 20 coping
      strategies she used to decrease the stress.

PMID- 24305908
TI  - Use of a sensory room on an intensive care unit.
AB  - This study explores the use of a sensory room on a psychiatric intensive care
      unit (PICU), with a particular focus on the effect on seclusion rates and staff
      and patients' experiences of using the sensory room. A mixed method research
      design was used, with the collection of seclusion data before and after a sensory
      room was introduced followed by qualitative interviews with staff and patients.
      No significant reduction in seclusion rates was noted with the introduction of
      the seclusion room. However, the interviews revealed a perception among staff
      that there had been a reduction in seclusion rates. Other findings from the
      interviews were that staff and patients viewed the sensory room as a positive
      therapeutic intervention, and use of the sensory room had improved staff-patient
      communication and patients' overall experience of the PICU. The use of a sensory
      room should be an intervention considered by other PICUs and inpatient
      psychiatric settings.

PMID- 24305909
TI  - Mobile apps for psychiatric nurses.
AB  - Many health care professionals, including psychiatric nurses, are faced with
      increasing questions from patients about mobile applications (apps). The purpose
      of this article is to give psychiatric-mental health nurses (PMHNs) an overview
      of the world of mobile health and medical apps to answer their own questions as
      well as those of their patients. Mobile apps will continue to evolve; thus, this
      article will serve as a base for PMHNs to build knowledge and understanding to
      help their patients.

PMID- 24305910
TI  - The nurse's role in primary care antidepressant medication adherence.
AB  - Depression remains one of the most common conditions seen in primary care
      settings. Antidepressant medications (ADMs) are considered standard treatment for
      moderate to severe depression, and in some instances, for minor depression. When
      ADM adherence is low, patients are at risk for treatment failure and poor quality
      of life. Nurses may be key in ensuring the success of ADM therapy; however,
      little is known about the interventions nurses use or the consequent patient
      outcomes. The objectives of this article were to identify studies in which nurses
      managed ADM adherence and to collect evidence about the efficacy of these
      interventions. A systematic literature review of clinical trial studies was
      conducted, which specifically included the role of the nurse. Nurse interventions
      identified were: patient care management, medication monitoring, depression
      education, and referrals to specialty providers. Nurses use a range of
      interventions to manage ADM adherence. In most studies, these approaches,
      including collaborative care, were efficacious.

PMID- 24305911
TI  - Combining ability and parental evaluation in five selected clones of sugarcane
      (Saccharum sp. hybrids).
AB  - Five Hawaiian commercial sugarcane (Saccharum sp. hybrids) clones were crossed in
      a full diallel. Four morphological characters were studied in the progeny: number
      of millable stalks per plant, stalk diameter, stalk length, and sucrose content.
      A fifth character, plant volume, was calculated from stalk number, stalk diameter
      and stalk length. The five selected parental clones were treated as fixed
      variables in the analysis. General combining ability (gca) was significant for
      all five characters; specific combining ability (sca) was significant for stalk
      diameter, stalk length, and plant volume. The variance for gca was large in all
      progeny populations. However, the variance for sca was large in the progeny of
      only some clones and/or for some individual characters. Parents were evaluated on
      the basis of their general combining ability: clone H49-3533 had high gca for
      sucrose content, while clone H53-5356 had high gca for plant vigor. 

PMID- 24305912
TI  - Characterization of X-ray induced increase of mitotic cross-overs in Glycine max.
AB  - Three types of spots can be identified on the leaves of heterozygous light green,
      Y/y, Glycine max (L.) Merrill: dark green (D) and aurea (A) single spots
      (resembling the phenotypes of the homozygotes) and double (Db) spots consisting
      of adjacent D and A tissue. X-irradiation increased the frequency of each type of
      spot on simple and first compound leaves. The Db spots, indicative of mitotic
      crossing-over (MCO), increase linearly with increasing dosage. Moisture content
      of the seeds was independent of the rate of spot increase. At high dosages
      morphological alterations were observed, including spots on homozygotes, leaf
      area reduction, smaller seedlings, and abnormal leaf shapes. The frequency of
      light green spots on normal dark green, Y/Y, seedlings was tabulated and, as with
      all other spot types, increased with increasing X-ray dosage. Dormant soybean
      seeds contain leaf primordia of both simple and first compound leaves. Mature
      simple leaves contained more spots, reflecting a larger primordial cell number,
      while first compound leaves had larger spots, since each affected cell underwent
      more mitoses prior to leaf maturation. Within first compound leaves, the terminal
      leaflets developed asynchronously in relation to the lateral leaflets. Terminal
      leaflets were shown to be initiated first, have a larger percentage of the
      leaflet area covered with spots, and have larger mature leaflet area. The
      spontaneous rate of MCO, 3.39*10(-5) MCO events per mitosis, was increased 282
      fold by 1600 R. We also ascertained that Mitomycin C is more specific for Db spot
      induction than X-rays. These results are compared with our similar irradiation
      experiments on tobacco shoot apices. 

PMID- 24305913
TI  - Desynapsis and spontaneous trisomy in jute (Corchorus olitorius L.).
AB  - Cytological studies in desynaptic plants, isolated at the F6 generation of an
      intervarietal cross of Corchorus olitorius L., have shown variable numbers of
      bivalents and univalents in the PMC's at metaphase I, resulting in irregular
      distribution of chromosomes at anaphase I. The progenies of the desynaptic plants
      consisted of 9.24 percent of all possible primary trisomies except trisomie 6.
      The desynaptic condition is controlled by a pair of simple recessive genes. 

PMID- 24305914
TI  - Haploidy from Hordeum interspecific crosses : Part 3: trihaploids of H.
      arizonicum and H. lechleri.
AB  - Hordeum arizonicum (2n=42) and H. lechleri (2n=42) were crossed with both H.
      bulbosum (2n=14 or 28) and H. vulgare (2n=14 or 28) and progeny plants were
      obtained through embryoculture. Crosses of arizonicum with diploid bulbosum
      invariably resulted in haploids (2n=21) of arizonicum, whereas arizonicum by
      tetraploid bulbosum or diploid vulgare crosses produced both hybrids and haploids
      of arizonicum. The lechleri by diploid bulbosum or diploid vulgare crosses
      resulted in haploids of lechleri, while lechleri by tetraploid bulbosum resulted
      in well differentiated embryos which failed to germinate.Hybrid embryos derived
      from the haploid producing crosses exhibit chromosome variability, suggesting
      that chromosome elimination leads to haploid formation.The results also indicate
      that the ratio of the parental genomes in the zygote is a critical factor which
      determines the chromosome elimination or stability in any cross combination.
      Furthermore, both arizonicum and lechleri appear to be of similar 'genetic
      strength' in eliminating bulbosum and vulgare chromosomes. The possibility of
      'stability factors' in overcoming elimination and manipulation towards
      elimination are discussed. 

PMID- 24305915
TI  - Combining ability and maternal effects in Brassica campestris L. var. 'yellow
      sarson'.
AB  - A diallel analysis of combining ability, including maternal effects, genotype X
      environment interaction and the progress under selection, is reported in three
      selected crosses of Brassica campestris L. var. 'yellow sarson', involving 15
      types, including 10 four-valved and 5 two-valved types from different parts of
      India. Twelve characters, including oil content, were studied in the f1
      generation.The investigation has revealed only marginal superiority of f1's over
      the parents for most of the characters related to yield. There was no relation
      between heterozygosity and stability of performance over environments for yield
      or its components or for oil content. Substantial maternal effects were observed
      which also interacted with environments. Creation of variation for primary and
      secondary branches would be essential for changing yield level in 'yellow
      sarson'. The presence of limited additive variation available for selection for
      yield components should be augmented by biparental mating the early segregating
      generations to break linkages, and was demonstrated by the recombinants obtained
      when this method was adopted.The magnitude of genotype - environment interactions
      in this study, as compared with the total genetic components for yield, oil
      content, number of siliquae on main axis and presence of large reciprocal
      variances in relation to general and specific combining ability variances for
      practically all characters, and the large interaction of [Formula: see text],
      narrowed down the expected effectiveness of selection.Biparental mating in the
      three best crosses yielded three new recombinants outyielding the best check T 10
      by the margins of 14%, 39% and 15%, respectively, in the yield trial. These
      recombinants had more primary branches and secondary branches, larger main axes
      and more siliquae with an increased number of seeds per siliqua, than any of the
      F1's in this study. 

PMID- 24305916
TI  - Electrophoretic survey of seedling esterases in wheats in relation to their
      phylogeny.
AB  - Evolutionary and ontogenetic variation of six seedling esterases of independent
      genetic control is studied in polyploid wheats and their diploid relatives by
      means of polyacrylamide gel electrophoresis. Four of them are shown to be
      controlled by homoeoallelic genes in chromosomes of third, sixth and seventh
      homoeologous groups.The isoesterase electrophoretic data are considered
      supporting a monophyletic origin of both the primitive tetraploid and the
      primitive hexaploid wheat from which contemporary taxa of polyploid wheats have
      emerged polyphyletically and polytopically through recurrent introgressive
      hybridization and accumulation of mutations. Ancestral diploids belonging or
      closely related to Triticum boeoticum, T. urartu, Aegilops speltoides and Ae.
      tauschii ssp. strangulata are genetically the most suitable genome donors of
      polyploid wheats. Diploids of the Emarginata subsection of the section Sitopsis,
      Aegilops longissima s.str., Ae. sharonensis, Ae. searsii and Ae. bicornis, are
      unsuitable for the role of the wheat B genome donors, being all fixed for the
      esterase B and D electromorphs different from those of tetraploid wheats. 

PMID- 24305917
TI  - Management of anastomotic leak: lessons learned from a large colon and rectal
      surgery training program.
AB  - BACKGROUND: Anastomotic leak is a dreaded surgical complication that can lead to
      significant morbidity and mortality. Despite its prevalence, there is no
      consensus on the management of anastomotic leak. This study aimed to review the
      management of anastomotic leak in the Division of Colon and Rectal Surgery at two
      institutions. METHODS: This is a retrospective review of all anastomotic leaks
      occurring after surgery in the Division of Colon and Rectal Surgery at two
      teaching institutions during 1997-2008. RESULTS: Altogether, 103 leaks occurred
      in 1,707 anastomoses (6 %), with a median time to diagnosis of 20 days (2-1,400
      days). The 90-day mortality rate was 3 %. The majority of cases were managed
      nonoperatively (73 %), and the majority of leaks were from an extraperitoneal
      anastomosis (67 %). Success (i.e., radiographic demonstration of a healed leak,
      restored gastrointestinal continuity) occurred in 54 % of operatively managed
      leaks and 57 % of nonoperatively managed leaks (56 % overall). Operative
      management differed by leak location. In 91 % of patients with intraperitoneal
      leaks, the anastomosis was resected. In 76 % of patients with extraperitoneal
      leaks, diversion and drainage alone was performed without manipulating the
      anastomosis. Nonoperative management was successful for 57 % of extraperitoneal
      leaks and 58 % of intraperitoneal leaks. There was no significant difference in
      the success rates based on type of management (operative/nonoperative) for either
      extraperitoneal or intraperitoneal leaks. CONCLUSIONS: Anastomotic leak continues
      to result in patient morbidity and mortality. Its diverse presentation requires
      tailoring management to the patient. Nonoperative and operative treatments are
      viable options for intraperitoneal and extraperitoneal leaks based on patient
      presentation.

PMID- 24305918
TI  - Ratio between proximal/distal gastroesophageal reflux does not discriminate
      abnormal proximal reflux.
AB  - INTRODUCTION: The threshold for pathologic proximal acid reflux is a
      controversial topic. Most values previously published are based on absolute
      numbers. We hypothesized that a relative value representing the quantitative
      relation between the amount of acid reflux that reaches proximal levels and the
      amount of distal reflux would be a more adequate parameter for defining
      pathologic proximal reflux. METHODS: We studied 20 healthy volunteers (median age
      30 years, 70 % women) without gastroesophageal reflux disease (GERD); 50 patients
      (median age 51 years, 60 % women) with esophageal symptoms of GERD (heartburn,
      regurgitation); and 50 patients (median age 49 years, 60 % women) with extra
      esophageal symptoms of GERD. All individuals underwent manometry and dual-probe
      pH monitoring. GERD was defined as a DeMeester score >14.7. The proximal/distal
      reflux ratio was calculated for all six parameters that constitute the DeMeester
      score. RESULTS: Absolute numbers for proximal reflux were not different for the
      three groups except for the number of episodes of reflux, which was higher for
      patients with GERD and esophageal symptoms than for patients with GERD and extra
      esophageal symptoms (p = 0.007). The number of episodes of distal reflux reaching
      proximal levels was significantly higher in volunteers than in all patients with
      GERD and significantly higher in patients with GERD and esophageal symptoms than
      in those with extra-esophageal symptoms. CONCLUSIONS: Our results suggest that
      the proximal/distal reflux ratio is not a good normative value for defining
      proximal reflux.

PMID- 24305919
TI  - Impact of surgery on quality of life in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Liver resection is the mainstay of curative treatment for localized
      hepatocellular carcinoma (HCC). However, the impact of surgery for HCC on quality
      of life (QOL) has not been well assessed. METHODS: Health-related QOL was
      assessed using the Short Form-36 questionnaire in 108 patients who underwent a
      liver resection for HCC between January 2004 and January 2008. The QOL assessment
      was scheduled before and every 3 months after the operation. Patients were
      divided into two groups based on patient-, tumor-, and surgery-related variables.
      The physical component summary (PCS) and mental component summary (MCS) were
      compared between the two groups. RESULTS: Altogether, 69 patients (64 %)
      completed the consecutive QOL assessments until 6 months after surgery. At 3
      months, the PCS scores were significantly lower for women and for patients who
      had undergone thoracotomy than among men (p = 0.010) and patients who had not
      undergone thoracotomy (p = 0.048), respectively. No significant differences in
      any of the PCS scores were observed at 6 months. No significant differences in
      the MCS scores were observed between the groups throughout the investigation, and
      improvement relative to the preoperative status was observed at 6 months.
      CONCLUSIONS: Physical impairments in the QOL after surgery had returned to the
      baseline at 6 months, and the postoperative mental QOL improved relative to the
      preoperative state. The surgical candidates were expected to have a satisfactory
      QOL regardless of the preoperative status and surgical outcomes. A
      thoracoabdominal approach had a transient negative impact on the physical health
      status.

PMID- 24305920
TI  - Characterizing the global burden of surgical disease: a method to estimate
      inguinal hernia epidemiology in Ghana: reply.

PMID- 24305921
TI  - Prognostic significance of the number of metastatic lymph nodes to stratify the
      risk of recurrence.
AB  - BACKGROUND: Prophylactic dissection facilitates identification of central lymph
      node (LN) metastasis in patients with papillary thyroid cancer (PTC). Because
      most staging systems do not stratify risks by the number of LN metastases,
      postoperative treatments vary among different institutions. Therefore we
      investigated the significance of number of LN metastases in risk stratification
      for recurrence in PTC. MATERIAL AND METHODS: A retrospective review was performed
      for 3,305 patients who had undergone thyroidectomy at Ajou University Hospital. A
      total of 2,462 patients (73.5 %) underwent total thyroidectomy, and another 3,152
      (94.1 %) underwent central LN dissection. Lateral cervical LN dissection had been
      performed in 420 patients (12.5 %). RESULTS: There were 115 patients with
      recurrence (3.4 %). Recurrence-free rates were 94.6 % at 5 years and 89.4 % at 10
      years. On univariate analysis, prognostic factors for recurrence were extent of
      thyroidectomy, tumor size, capsular invasion, T stage, N stage, number of LN
      metastasis, TNM stage, and radioactive iodine (RAI) therapy. On multivariate
      analysis, number of LN metastasis and N stage were significant prognostic factors
      for recurrence. Recurrence-free rate was significantly different between patients
      with 0-1 LN and those with 2 or more LN. CONCLUSIONS: Number of metastatic LN was
      a significant prognostic factor, in addition to the N stage. Therefore, number of
      metastatic LN must be considered for postoperative staging system to tailor
      treatment and follow-up recommendations. In addition, patients with >=2
      metastatic LN may benefit from total thyroidectomy and RAI therapy with
      postoperative follow-up with serum thyroglobulin.

PMID- 24305922
TI  - The outcomes of percutaneous versus open placement of peritoneal dialysis
      catheters.
AB  - BACKGROUND: Peritoneal dialysis catheters (PDCs) can be inserted by a
      percutaneous, open surgical, or laparoscopic approach. Considerable controversy
      surrounds the mode of catheter placement and its impact on technical success. We
      compared the complications and survival characteristics of PDCs that were
      inserted by the open approach versus those inserted percutaneously. METHODS: We
      reviewed the outcomes of 167 patients who received PDCs between September 2009
      and February 2012. Of these, 89 were placed percutaneously and 78 were placed by
      open surgical techniques. The mechanical complication rates, including catheter
      bleeding, wrapping, migration, leakage, and technical failure of intraperitoneal
      placement were compared between the two groups. Additionally, peritonitis
      episodes, exit site infection rates, and tunnel infection rates were compared
      between groups. RESULTS: The incidence of one or more previous intra-abdominal
      surgeries was significantly higher in the open group (4.5 percutaneous vs 21.7 %
      open; P = 0.001). Although the overall number of complications did not differ
      between the two groups, the incidence of early mechanical complications (11.2 vs
      0 %; P = 0.002) and the number of catheter removals due to mechanical
      complications (7.9 vs 1.3 %; P = 0.047) were higher in the percutaneous group. Of
      the 15 mechanical complications in the percutaneous group, one third were due to
      technical failures compared to none in the open group (5.6 vs 0 %; P = 0.034).
      The 1 year survival rate of the PDCs for the percutaneous and open groups was
      89.9 and 93.3 %, respectively (P = 0.249). CONCLUSIONS: The placement modality
      did not affect catheter survival. However, early mechanical complications,
      including technical failures, were more frequent in the percutaneous group,
      despite the proportion of patients with a history of one or more previous intra
      abdominal surgeries being significantly lower in that group. The direct
      visualized open method of catheter insertion may provide the most reliable and
      secure access for a PDC.

PMID- 24305923
TI  - Lobectomy and prophylactic central neck dissection for papillary thyroid
      microcarcinoma: do involved lymph nodes mandate completion thyroidectomy?
AB  - BACKGROUND: The present study was designed to investigate the necessity of
      completion thyroidectomy for patients who underwent thyroid lobectomy for low
      risk papillary thyroid microcarcinoma (PTMC) that was later pathologically
      diagnosed as central lymph node (CLN) metastasis. METHODS: Between 1986 and 2001,
      we assessed 551 patients who underwent thyroidectomy with prophylactic
      ipsilateral central compartment neck dissection, and 409 patients were followed
      up completely. Thyroid lobectomy were performed in 281 and 128 patients,
      respectively. The patients were divided into two groups according to CLN
      metastasis. Clinicopathological profiles and follow-up details were investigated
      by retrospective chart review. RESULTS: The CLN-positive and -negative groups
      were comprised of 43 (15.2 %) and 238 patients (84.8 %), respectively. The mean
      ages of the two groups were not significantly different (p > 0.05). The mean
      tumor size of the CLN-positive group (6.8 mm) was significantly larger than that
      of the CLN-negative group (5.6 mm; p < 0.05). Microscopic capsular invasion was
      significantly higher in the CLN-positive group (51.2 vs. 23.9 %; p < 0.05).
      Overall, 21 patients (7.4 %, 21/281) experienced recurrence. Among these, 2 (4.7
      %, 2/43) and 19 (8.0 %, 19/238) were in the CLN-positive and -negative groups,
      respectively. There was no significant correlation between CLN metastasis and
      tumor recurrence. CONCLUSIONS: Postoperative recurrence was lower in the CLN
      positive group, and there was no significant correlation between CLN metastasis
      and tumor recurrence. Our results suggest that it is not necessary to perform
      completion thyroidectomy for PTMC patients who have undergone thyroid lobectomy
      and who have been pathologically diagnosed with CLN metastasis.

PMID- 24305924
TI  - Postoperative PTH measurement is not a reliable predictor for hypocalcemia after
      total thyroidectomy in vitamin D deficiency: prospective study of 203 cases.
AB  - BACKGROUND: Several factors have been used to predict post total thyroidectomy
      (TT) hypocalcemia. Serum intact PTH (PTH) levels <10 pg/mL after TT is considered
      to be the most accurate predictor. The aim of the present study was to evaluate
      the accuracy of PTH as a predictor of post-TT hypocalcemia in patients with
      vitamin D deficiency. MATERIALS AND METHODS: The present prospective study was
      conducted from 2009 to 2011 and included patients undergoing TT for benign
      goiter. The PTH levels 8 h after TT in patients who were vitamin D sufficient
      (group A; S Vit D >20 ng/mL) versus those who were vitamin D deficient (group B)
      were compared. Comparison was also performed between patients belonging to group
      A and group B who developed hypocalcemia. Appropriate statistical tests were
      applied. RESULTS: A total of 203 patients (19 males, 184 females) underwent TT;
      58.6 % (n = 119) belonged to group A and 41.4 % (n = 84) to group B. Their mean
      age was 36.81 +/- 12.9 years, and the mean duration of goiter was 45.35 +/- 54.6
      months. Hypocalcemia occurred in 41 patients (20.2 %). Among them 15 belonged to
      group A and 26 to group B (p = 0.002). The mean PTH in patients who developed
      hypocalcemia was 12.75 +/- 8.91 versus 22.58 +/- 15.38 in those who did not
      develop hypocalcemia (p = 0.00). Furthermore it was seen that the mean PTH in
      vitamin D sufficient hypocalcemic patients (n = 15) was 7.12 +/- 1.79 and that in
      vitamin D deficient hypocalcemic patients (n = 26) was 16 +/- 9.77 (p = 0.001)
      CONCLUSIONS: Our findings suggest that the fall in PTH after TT in vitamin D
      deficient patients is unreliable in predicting hypocalcemia and should not be
      relied on to plan early postoperative discharge.

PMID- 24305925
TI  - Tomasz Drobnik (1858-1901)--an assistant who equalled his masters.

PMID- 24305926
TI  - Tissue expander-assisted ventral hernia repair for the skin-grafted damage
      control abdomen.

PMID- 24305927
TI  - Clinical analysis of anatomical resection for the treatment of hepatocellular
      carcinoma based on the stratification of liver function.
AB  - BACKGROUND: This study aimed to clarify the efficacy of anatomical resection (AR)
      for the treatment of hepatocellular carcinoma (HCC) compared with that of
      nonanatomical resection (NAR) based on the stratification of liver function (LF).
      METHODS: The clinical records of 174 patients with a single HCC, 2-5 cm in
      diameter and without macroscopic vascular invasion, were analyzed. AR was
      performed in 132 patients and NAR was performed in 42 patients. The indocyanine
      green retention rate at 15 min (ICGR15) of the 78 patients classified as the good
      LF group was 10-20 % and the ICGR15 of the 54 patients classified as the poor-LF
      group was 20-40 %. RESULTS: The 5-year overall survival (OS) and disease-free
      survival rates of the 174 patients were 67.6 and 33.4 %, respectively. Cox
      proportional hazard analysis identified ICGR15 >= 20 %, liver cirrhosis, alpha
      fetoprotein >= 100 mg/dL, and infiltrating growth as independent prognostic
      factors. Liver cirrhosis was significantly less frequent in patients who
      underwent AR than in patients who underwent NAR (52 vs. 79 %, p = 0.002). In the
      subgroup analysis of the good-LF group, there were no significant differences in
      5-year OS after AR and NAR (73.3 vs. 65.2 %, p = 0.857). By contrast, in the
      subgroup analysis of the poor-LF group, the 5-year OS after AR was significantly
      worse than after NAR (45.3 vs. 77.4 %, p = 0.044). CONCLUSION: In patients with
      an ICGR15 >= 20 %, we recommend NAR rather than AR for the treatment of a
      solitary 2-5-cm-diameter HCC and without macroscopic vascular invasion.

PMID- 24305928
TI  - Intraoperative neuromonitoring for surgical training in thyroid surgery: its
      routine use allows a safe operation instead of lack of experienced mentoring.
AB  - BACKGROUND: The aim of the present study was to evaluate the influence of
      intraoperative neuromonitoring (NM) on surgical training. The results of
      thyroidectomy performed by inexperienced surgeons under the supervision of a
      consultant surgeon without intraoperative neuromonitoring (ioNM) were compared to
      those of the operations performed without experienced assistance but under
      neuromonitoring control. MATERIALS AND METHODS: The study included the thyroid
      operations performed in our Department between 2005 and 2012. Among them,
      residents or fellows performed 1,116 procedures. Seven hundred sixty-five
      operations were conducted without neuromonitoring (NV group) and 351 with NM
      group. In the NV group 375 unilateral and 390 bilateral operations were
      performed. In the NM group 149 unilateral and 202 bilateral operations were
      performed. Primary end point of the study was the incidence of postoperative
      recurrent laryngeal nerve palsy. A secondary end point was the impact of ioNM on
      operating time and operative strategy. RESULTS: The incidence of recurrent
      laryngeal nerve (RLN) palsy was 2.6 % in the NV group and 2.7 % in the NM group
      [p = ns]. One case of bilateral RLN palsy was observed in the NV group. The
      operative time was longer in the NM group for both lobectomy and total
      thyroidectomy (50 vs. 56 min and 76 vs. 81 min, respectively; p < 0.05).
      CONCLUSIONS: The routine use of intermittent intraoperative neuromonitoring
      during thyroid operations does not reduce the incidence of RLN palsy.
      Nevertheless, it allows inexperienced surgeons to perform a safe operation with a
      complication rate comparable to that obtained under supervision of an experienced
      surgeon. Moreover, ioNM could avoid the unfortunate occurrence of a bilateral RLN
      palsy.

PMID- 24305929
TI  - In hepatocellular carcinomas, any proportion of poorly differentiated components
      is associated with poor prognosis after hepatectomy.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) often consists of various
      differentiation components in a single tumor. However, the categorization of
      histologic grade in hepatectomy for those tumors has not been standardized. Some
      studies have determined the differentiation grade of the tumor according to its
      worst component, whereas others have determined it according to its predominant
      component. The present study aimed to resolve the controversy about whether the
      worst component or the dominant component determines the nature of the tumor,
      especially focusing on the presence of a poorly differentiated component (PDC).
      METHODS: In total, 427 hepatectomized patients with solitary HCC were divided
      into three groups, tumors without a PDC (NP), tumors with a PDC but dominantly
      consisting of non-PDC as poorly contained (PC), and tumors predominantly
      consisted of a PDC as poorly dominant (PD). PC was compared with PD and NP.
      RESULTS: Statistical analysis revealed that large tumors and high alpha
      fetoprotein level were significantly more frequent in PC than in NP (P < 0.01 and
      P = 0.04, respectively), although no remarkable difference was observed between
      PC and PD. Both recurrence-free and overall survival rates were significantly
      worse in the PC and PD groups than in the NP group (PC vs. NP: P = 0.01 and P <
      0.01, PD vs. NP: P < 0.01 and P < 0.01, respectively), but there was no
      significant difference in these parameters between PC and PD. CONCLUSIONS: All
      HCC, including PDC, should be categorized as poorly differentiated HCC regardless
      of the predominant differentiation component.

PMID- 24305930
TI  - Morbidity of chemotherapy administration and satisfaction in breast cancer
      patients: a comparative study of totally implantable venous access device (TIVAD)
      versus peripheral venous access usage.
AB  - BACKGROUND: This prospective, non-randomized, comparative study evaluated
      morbidity of chemotherapy administration via a totally implantable venous access
      device (TIVAD) versus peripheral intravenous access (PIVA), and satisfaction in
      breast cancer patients in a limited-resource setting. METHODS: Consecutive
      patients receiving chemotherapy via TIVAD (n = 114) or PIVA (n = 159) were
      studied. Venous access-related events were recorded. Morbidity and satisfaction
      with TIVAD or PIVA as perceived by the patients were assessed using a
      specifically designed questionnaire, which patients filled after 1st cycle of,
      and after completion of all chemotherapy. RESULTS: Patients in the two groups
      were of comparable age, body mass index, and disease stage. Acceptance of TIVAD
      was higher in literate patients. TIVAD did not interfere with sleep or activities
      in 90 % of patients. The majority (81.2 %) were satisfied with the cosmetic
      outcome, 91.5 % would have TIVAD re-inserted if the need arose, and 89.6 % would
      recommend it to others. Non-fatal complications occurred in 16 patients, and
      TIVAD had to be removed prematurely in five patients. In the PIVA group, 40 %
      needed multiple needle pricks and 55.8 % developed thrombophlebitis or staining
      of arms. Drug extravasation and ulceration were suffered by 8.3 and 4.2 %,
      respectively. However, 78.3 % of patients reported no interference with daily
      activities and only 26 % would prefer a TIVAD. Those receiving more than six
      chemotherapy cycles were dissatisfied to a greater extent with PIVA (p < 0.05).
      CONCLUSIONS: Breast cancer chemotherapy via TIVAD is safe and convenient and
      results in high satisfaction levels, although it involves additional expenditure.
      Chemotherapy via PIVA is acceptable, albeit with lower satisfaction, more so in
      those receiving more than six chemotherapy cycles.

PMID- 24305931
TI  - Reoperative experience with papillary thyroid cancer.
AB  - BACKGROUND: Intense postoperative monitoring has resulted in increasing detection
      of patients with recurrent papillary thyroid cancer (PTC). Our goals included
      quantifying successful reoperation, and analyzing surgical complications and
      reasons for relapse. METHODS: From 1999 to 2008, a total of 410 patients
      underwent reoperation for PTC relapse. We analyzed post-reoperative disease
      outcomes, reasons for relapse, and complications. RESULTS: Bilateral reoperative
      thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central
      neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node
      dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II-V
      dissection, 93 (23 %); levels III-V, 86 (21 %); lateral single- or two
      compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53
      (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism,
      3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve
      injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of
      380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are
      alive with no structural evidence of disease, 38 % developed disease relapse
      (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease.
      The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18
      (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of
      these two reasons in 10 (3 %), and disease virulence (local or systemic
      recurrence) in 81 (21 %). CONCLUSIONS: Although 72 % of patients were rendered
      structurally disease free after reoperation, nearly 40 % suffered additional
      relapse. Improved surgical technique or preoperative localization might
      positively affect 15-20 %; at least 20 % reflect the biologic aggressiveness of
      the disease.

PMID- 24305932
TI  - Feasibility of laparoscopic re-resection for patients with recurrent
      hepatocellular carcinoma.
AB  - BACKGROUND: Repeated resection via an open approach is an effective treatment for
      post-operative recurrent hepatocellular carcinoma (HCC). However, there are
      limited data on the application of laparoscopic approach for recurrent HCC in
      patients with prior liver resections. The aim of this study was to review our
      experience of laparoscopic re-resection in patients with postoperative tumor
      recurrence. MATERIALS AND METHODS: A total of 11 patients received laparoscopic
      re-resections for postoperative tumor recurrence in our center. Data were
      reviewed for demographics, tumor characteristics, and perioperative outcomes.
      Case-match analysis with the open approach was performed in a 1:2 ratio. RESULTS:
      Six patients had their first liver resection carried out via the open approach
      and the remaining five patients received the laparoscopic approach. The recurrent
      tumor size was 20 mm (12-50 mm) and ten patients had a solitary recurrence. Two
      patients had laparoscopic left lateral sectionectomy and the remaining nine
      patients had sub-segmentectomies. There was no significant difference in patient
      characteristics, preoperative liver function, and tumor features between the
      laparoscopic and open groups. Perioperative blood loss was significantly reduced
      in the laparoscopic group (100 vs. 314 mL; p = 0.014) but the morbidity rate
      (18.2 vs. 4.5 %; p = 0.199) and length of hospitalization were comparable (6 vs.
      5 days; p = 0.831). The 3-year overall survival rates for the laparoscopic and
      open groups were 60.0 and 89.3 %, respectively (p = 0.279). CONCLUSION: Our study
      showed that laparoscopic re-resection for recurrent HCC was feasible with
      satisfactory postoperative and oncological outcomes, even in patients with
      previous major liver resections.

PMID- 24305933
TI  - Modified laparoscopic splenic vessel-preserving distal pancreatectomy: Matador
      assistance and peel-away technique.
AB  - BACKGROUND: Laparoscopic splenic vessel-preserving distal pancreatectomy (lap
      SVPDP) is a popular procedure in pancreatic surgery. However, postoperative
      complications include false aneurysms of the splenic artery, splenic vein
      stenosis and thrombosis, pancreatic fistulas, abscess, and perigastric varices.
      METHODS: Eight patients (three men, five women, average age 66.1 years) with
      benign tumors underwent lap-SVPDP. Lap-SVPDP was performed in the lithotomy
      position with the head slightly elevated. The splenic vein was peeled
      longitudinally toward the pancreatic tail. A vessel-sealing system was used to
      detach the pancreatic body from the greater omentum, and the pancreas was
      transected using a surgical stapler. RESULTS: Mean operation time was 254 min;
      mean blood loss was 163 ml; and mean post-surgical hospitalization time was 13
      days. No postoperative bleeding from the preserved splenic vessels occurred, and
      there were no splenic infarcts or splenic abscesses. CONCLUSIONS: For safe
      performance of lap-SVPDP, the posterior surface of the pancreas should be
      completely exposed. The splenic vein should be 'peeled away', starting from its
      central rear, enabling easy detection of its course to avoid inadvertent sealing.
      With improved operational techniques, lap-SVPDP can be adopted as a standard
      procedure in pancreatic surgery.

PMID- 24305934
TI  - Assessing patterns of practice of sentinel lymph node biopsy for breast cancer in
      Latin America.
AB  - INTRODUCTION: There is a lack information regarding how sentinel lymph node
      biopsy (SLNB) for breast cancer is carried out today in developing countries and
      how it was adapted. To rectify this situation we performed a pattern-of-practice
      survey amongst practicing surgeons in Latin America (LA). METHODS: A survey was
      developed to assess current surgical practice in breast cancer, use of SLNB,
      limitations to the implementation, training, technique variations, and observed
      adverse events. A total of 30 surgical associations and breast surgery societies
      in 18 Latin American countries were invited to participate. Surveys were
      distributed among member of these associations and 76.7 % of those contacted
      answered the survey. Responses were limited only to those who reported treating
      breast cancer patients. RESULTS: A total of 463 surgeons who manage breast cancer
      responded. Over 53 % of surgeons do not have sub-specialty training. Only 47.7 %
      have a high-volume case load, of which 87.8 % routinely perform SLNB. The main
      limitations perceived to the implementation of SLNB were a lack of
      resources/equipment (48 %) and training opportunities (33 %). Over 60 % reported
      that fewer than half of their patients were eligible for SLNB and 67.8 % reported
      that they were involved in teaching this technique to residents. CONCLUSIONS: A
      significant proportion of surgeons that treat breast cancer cases in LA have not
      had sub-specialty training or manage a low volume of cases. Among those surgeons
      with a high-volume caseload, SLNB is routinely performed. SLNB training during
      residency represents an opportunity for improvement in the region.

PMID- 24305935
TI  - Neoadjuvant therapy and vascular resection during pancreaticoduodenectomy:
      shifting the survival curve for patients with locally advanced pancreatic cancer.
AB  - BACKGROUND: Neoadjuvant therapy and vascular resection may offer patients with
      locally advanced pancreatic cancer potential cure. METHODS: We reviewed medical
      records of patients with ductal adenocarcinoma who underwent
      pancreaticoduodenectomy (PD) from 1992 through 2011. We identified patients who
      received neoadjuvant therapy (NA+) or required vascular resection (VR+) for
      locally advanced disease and compared outcomes to those who did not. RESULTS: Of
      the 643 patients who were initially explored, 506 (143 NA+ and 363 NA- patients)
      ultimately underwent PD. There were no significant differences in R0 resection or
      morbidity. Mortality was higher in the NA+ versus NA- group (7.0 vs 3.0 %, p =
      0.04). More NA+ patients underwent PD VR+ (p < 0.001). Among VR+ patients,
      neoadjuvant therapy resulted in significantly lower R1 resection. Among resected
      patients, survival of NA+ patients was significantly longer than both NA-
      patients (27.3 vs 19.7 months, p < 0.05) and patients abandoned because of
      locally advanced disease. Age, tumor grade, lymph node ratio, and R1 resection
      were independent predictors of poor survival. CONCLUSIONS: Neoadjuvant therapy
      and vascular resection offer patients with locally advanced pancreatic cancer the
      chance for cure with acceptable morbidity and mortality. These patients have
      improved survival over patients deemed locally inoperable by traditional
      criteria.

PMID- 24305936
TI  - Prognostic value of CEA and CK20 mRNA in the peritoneal lavage fluid of patients
      undergoing curative surgery for gastric cancer.
AB  - BACKGROUND: Peritoneal recurrence is the most common type of recurrence in
      gastric cancer. Although cytological examination of peritoneal lavage fluid has
      been used to predict peritoneal spread, peritoneal recurrences often occur even
      in patients with negative cytology. Our previous retrospective study suggested
      that reverse transcriptase-polymerase chain reaction (RT-PCR) using peritoneal
      lavage fluid may be useful for predicting peritoneal recurrence in patients with
      negative cytology. This prospective study was conducted to validate the clinical
      impact of this RT-PCR method. METHODS: From July 2009 to June 2012, a total of
      118 cT2-4 gastric cancer patients underwent surgery. Since 14 patients were
      ineligible because they had incurable factors, the remaining 104 eligible
      patients were evaluated for carcinoembryonic antigen (CEA) and cytokeratin 20
      (CK20) messenger RNA (mRNA) using RT-PCR. If either CEA or CK20 mRNA was detected
      by RT-PCR, the patient was defined as PCR-positive as in our previous study. The
      association between recurrence-free survival (RFS) and background factors was
      analyzed using Cox proportional hazards models. RESULTS: Of 104 patients, 16
      (15.4 %) were positive for either CEA or CK20. PCR-positive patients had
      significantly worse RFS than PCR-negative patients (log-rank p = 0.007).
      Regarding the pattern of recurrence, 4 of 16 (25 %) PCR-positive patients and 2
      of 88 (2 %) PCR-negative patients had peritoneal recurrence (p < 0.001), but
      there were no significant differences in recurrence at other sites. Cox
      multivariate analysis indicated only PCR-positivity as a significant predictor of
      poor RFS (p = 0.029). CONCLUSION: This prospective study demonstrated that CEA
      and CK20 PCR results could predict peritoneal recurrence after curative surgery.

PMID- 24305937
TI  - Low nutritional prognostic index correlates with poor survival in patients with
      stage IV colorectal cancer following palliative resection of the primary tumor.
AB  - BACKGROUND: We retrospectively investigated the prognostic significance of
      various clinicopathological factors and preoperative nutritional status to select
      patients with stage IV colorectal cancer (CRC) who will have a poor prognosis
      after palliative resection of the primary tumor. METHODS: A total of 100 stage IV
      CRC patients who underwent palliative resection were enrolled. Various
      clinicopathological factors and Onodera's prognostic nutritional index (OPNI)
      were evaluated to identify any possible relationship with the prognosis. RESULTS:
      At the time of the analysis, 83 patients had died, and the median survival time
      was 21 months. Of the 100 patients, 24 had primary tumor-related symptoms such as
      obstruction or bleeding. No significant correlation was noted between the OPNI
      and various clinicopathological factors. The multivariate analysis of patients
      without primary tumor-related symptoms revealed that the OPNI was an independent
      prognostic factor. The overall survival of the low-OPNI group was significantly
      worse than that of the high-OPNI group. CONCLUSIONS: This retrospective study
      suggested that patients with a low OPNI may not be candidates for palliative
      resection, because it provides no survival benefit to these patients.

PMID- 24305938
TI  - A simple risk score to predict the presence of non-sentinel lymph node metastases
      in breast cancer patients with a positive sentinel node.
AB  - BACKGROUND: Historically, completion axillary lymph node dissection (cALND) is
      recommended in sentinel lymph node (SLN)-positive patients. However, the high
      rate of negative non-sentinel nodes (NSNs) in cALND and the reported low axillary
      recurrence rates have led to a more conservative approach. A risk score was
      developed to identify a patient's individual risk for NSN metastases. METHODS:
      Data of 182 SLN-positive patients who underwent cALND were used for risk score
      development. The risk score, consisting of pathological tumor size (<= 20/>20
      mm), lymphovascular invasion (no/yes), extracapsular extension (no/yes), size of
      metastases (<= 2/>2 mm), and number of positive SLNs (1/>1), was subsequently
      validated on an external population (n = 180). RESULTS: The area under the
      receiver operating characteristic curve was 0.78 (95 % CI 0.71-0.85) in the
      original population and 0.78 (95 % CI 0.70-0.85) in the validation population.
      Based on the predicted risk for positive NSNs, three groups were defined: low
      risk (<= 20 %), intermediate risk (21-50 %), and high risk (>50 %). In total, 88
      patients met the Z0011 inclusion criteria and none of them had a high predicted
      risk. Of the 199 non-Z0011 patients, 67 (33.7 %) had low risk, 96 (48.2 %) had
      intermediate risk, and 36 (18.1 %) had high risk. CONCLUSION: A simple risk
      score, integrating just five clinicopathological variables, was developed that
      may assist in individual decision making regarding ALND in SLN-positive patients
      outside of the Z0011 trial.

PMID- 24305939
TI  - Gastrocele complicates the course of non-operated severe caustic injuries:
      operative strategies.
AB  - BACKGROUND: For selected cases of severe caustic injuries, evidence favors
      conservative management, consisting of radiographic and clinical observation
      without emergency surgery. However, this approach can lead to the development of
      gastric distension caused by combined esophageal and antral strictures, called
      gastrocele. This study assessed the safety of a two-stage surgical treatment for
      gastrocele. METHODS: Patients treated in our department between 2004 and 2010 for
      caustic injury who did not receive emergency surgery and subsequently developed
      gastrocele were retrospectively analysed. Demographic information, symptoms, and
      ingestion history were documented. Surgical management included partial
      gastrectomy and postponed esophageal stricture treatment. Outcome measures
      included postoperative morbidity and mortality. RESULTS: Eight nonoperated
      patients with severe caustic injury from suicidal ingestions of caustic
      substances were found to have developed gastrocoele. They presented with mostly
      endoscopic stage IIIb esophageal and gastric injuries. All patients had clinical
      symptoms of vomiting and abdominal tenderness at day 8 after caustic ingestion.
      Antrectomy and esophageal stricture treatment were performed at an average of 2
      and 8 months, respectively, after caustic ingestion. There were no postoperative
      deaths, and the long-term survival rate was 83 %. CONCLUSIONS: Gastrocele should
      be suspected in patients with stage III gastric and esophageal injuries who have
      been treated by conservative management and are still vomiting more than 1 week
      postingestion. A two-staged surgical strategy of antrectomy followed by a
      postponed esophageal stricture treatment was found to be safe and effective for
      these patients.

PMID- 24305940
TI  - Health-related quality of life after robot-assisted distal gastrectomy in early
      gastric cancer.
AB  - PURPOSE: This study was designed to assess the chronological change in health
      related quality of life (HRQOL) following robot-assisted distal gastrectomy
      (RADG) for early gastric cancer (EGC) and to compare the HRQOL of the patients
      undergoing RADG with that of the general population. METHODS: Patients undergoing
      RADG for EGC between March 2010 and May 2011 were enrolled. The European
      Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ
      C30) and the gastric cancer-specific module (QLQ-STO22) were completed before the
      operation and at 1 week as well as 1, 3, 6, and 12 months postsurgery. HRQOL data
      of the enrolled patients were compared to reference values obtained from the
      general population. RESULTS: A total of 30 patients were enrolled, and the
      overall compliance for questionnaire response was 94.4 %. The worst scores for
      most of the domains were observed at 1 week postsurgery and usually returned to
      baseline levels within 3 months, except for fatigue, dysphagia, pain, and eating
      restriction. Diarrhea was the only symptom that did not recovered after 1 year.
      Before surgery, patients reported significantly worse social function and
      financial difficulties compared to the general population, which persisted for 1
      year postsurgery. CONCLUSIONS: The immediate deterioration of HRQOL after RADG
      was restored to baseline levels within 3 months postsurgery in the majority of
      the patients. Robotic assistance might aid in the rapid recovery of global health
      status after surgery in EGC patients. Prolonged impairment in social function
      compared with the general population suggests that psychological support is
      necessary even for EGC patients.

PMID- 24305941
TI  - Response to letter-to-the-editor Surgical care: addressing the barriers to access
      in low-income countries.

PMID- 24305942
TI  - Surgical treatment of 144 cases of hilar cholangiocarcinoma without liver-related
      mortality.
AB  - BACKGROUND: The present study evaluated whether the short- and long-term outcomes
      improved during our 23 years of experience treating 144 consecutive patients with
      hilar cholangiocarcinoma. METHODS: Patients treated between 1990 and 2000 (period
      1; n = 70) were retrospectively compared with those treated between 2001 and 2012
      (period 2; n = 74). Mortality and major complications were defined as any death
      occurring within 90 days of surgery and a grade III-IV complication according to
      the Clavien classification, respectively. RESULTS: The mortality and major
      complication rates decreased from 1.2 and 34 % during period 1-0 and 24 % during
      period 2, respectively. Although the surgical procedure was comparable between
      the two periods, the median blood loss was significantly reduced from 1,020 mL
      during period 1-745 mL during period 2 (P = 0.003), and blood loss was the only
      significant predictor of postoperative morbidity in a multivariable analysis. The
      R0 resection rate (70 vs. 78 %, P = 0.250) and the 5-year survival rate (33 vs.
      35 %, P = 0.529) were similar for the two periods. A multivariable analysis
      identified positive nodal involvement and R1-2 resection as independent
      prognostic factors for survival. CONCLUSIONS: The perioperative outcomes after
      surgical treatment for hilar cholangiocarcinoma have steadily improved through
      the accumulation of experience and meticulous surgical techniques to reduce blood
      loss. Further improvement of the R0 resection rate could prolong patient
      survival.

PMID- 24305944
TI  - Improved clinical control of a challenging case of Behcet's disease with
      rituximab therapy.
AB  - Behcet's disease (BD) is a rare form of vasculitis in North America. Like other
      rare diseases, there is no high-quality evidence for biologic use beyond case
      reports/series, and thus, therapy remains controversial. We report on the case of
      a patient who failed to respond to conventional therapy with colchicine and
      NSAIDs. She responded to steroids but failed to tolerate steroid tapers despite
      azathioprine, methotrexate, infliximab, and etanercept and required chronic
      prednisone up to 20 mg daily due to recurrent severe mucosal ulcers with fever,
      erythema nodosum (EN), and arthritis. She received cyclophosphamide for another
      indication but even then failed steroid taper. After three courses of rituximab,
      she showed marked clinical improvement and was able to reduce prednisone to 8 mg
      and to return to school and work. A review of disease mechanisms and clinical
      literature is presented for those facing challenging cases where evidence is
      limited. 

PMID- 24305945
TI  - Anakinra treatment in drug-resistant Behcet's disease: a case series.
AB  - The study objective was to report treatment with an interleukin (IL)-1 receptor
      antagonist, anakinra, in patients with multiorgan Behcet's disease (BD).
      Comparison of clinical manifestations, previous treatments, markers of
      inflammation, concomitant medications, treatment regimen modifications, relapses,
      and adverse events before and during anakinra administration among patients with
      BD were evaluated. Nine BD patients (mean age 34.55 +/- 16.30 years) refractory
      to tumor necrosis factor blockers and standardized therapies are reported in our
      survey. Their mean age at disease onset was 25 +/- 13.88 years and their overall
      disease duration was 9.55 +/- 5.33 years. All patients were positive for the HLA
      B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out
      of nine patients promptly responded, and most of them were maintained on 100 mg
      of daily anakinra with low doses of prednisone. However, most patients
      experienced a relapse in one or more clinical manifestations over time (mean time
      to relapse 29 +/- 21.65 weeks), and only one patient remained completely under
      control on anakinra monotherapy. Despite a relapse in one or more disease
      manifestations, treatment was continued in most patients for a mean period of
      13.75 +/- 6.49 months. No serious adverse events occurred. Eight out of nine
      refractory BD patients showed a prompt improvement after starting anakinra,
      supporting the concept that IL-1 plays a pathological role in this disease.
      Nevertheless, after several months, most patients experienced a relapse. It
      remains unclear whether increasing the dose of anakinra would have prevented the
      reoccurrence of disease activity.

PMID- 24305946
TI  - BAG-6, a jack of all trades in health and disease.
AB  - BCL2-associated athanogene 6 (BAG-6) (also Bat-3/Scythe) was discovered as a gene
      product of the major histocompatibility complex class III locus. The Xenopus
      ortholog Scythe was first identified to act as an anti-apoptotic protein.
      Subsequent studies unraveled that the large BAG-6 protein contributes to a number
      of cellular processes, including apoptosis, gene regulation, protein synthesis,
      protein quality control, and protein degradation. In this context, BAG-6 acts as
      a multifunctional chaperone, which interacts with its target proteins for
      shuttling to distinct destinations. Nonetheless, as anticipated from its genomic
      localization, BAG-6 is involved in a variety of immunological pathways such as
      macrophage function and TH1 response. Most recently, BAG-6 was identified on the
      plasma membrane of dendritic cells and malignantly transformed cells where it
      serves as cellular ligand for the activating natural killer (NK) cell receptor
      NKp30 triggering NK cell cytotoxicity. Moreover, target cells were found to
      secrete soluble variants of BAG-6 and release BAG-6 on the surface of exosomes,
      which inhibit or activate NK cell cytotoxicity, respectively. These data suggest
      that the BAG-6 antigen is an important target to shape a directed immune response
      or to overcome tumor-immune escape strategies established by soluble BAG-6. This
      review summarizes the currently known functions of BAG-6, a fascinating
      multicompetent protein, in health and disease. 

PMID- 24305947
TI  - Inhibition of Ku70 acetylation by INHAT subunit SET/TAF-Ibeta regulates Ku70
      mediated DNA damage response.
AB  - DNA double-strand breaks (DSBs) can cause either cell death or genomic
      instability. The Ku heterodimer Ku70/80 is required for the NHEJ (non-homologous
      end-joining) DNA DSB repair pathway. The INHAT (inhibitor of histone
      acetyltransferases) complex subunit, SET/TAF-Ibeta, can inhibit p300- and PCAF
      mediated acetylation of both histone and p53, thereby repressing general
      transcription and that of p53 target genes. Here, we show that SET/TAF-Ibeta
      interacts with Ku70/80, and that this interaction inhibits CBP- and PCAF-mediated
      Ku70 acetylation in an INHAT domain-dependent manner. Notably, DNA damage by UV
      disrupted the interaction between SET/TAF-Ibeta and Ku70. Furthermore, we
      demonstrate that overexpressed SET/TAF-Ibeta inhibits recruitment of Ku70/80 to
      DNA damage sites. We propose that dysregulation of SET/TAF-Ibeta expression
      prevents repair of damaged DNA and also contributes to cellular proliferation.
      All together, our findings indicate that SET/TAF-Ibeta interacts with Ku70/80 in
      the nucleus and inhibits Ku70 acetylation. Upon DNA damage, SET/TAF-Ibeta
      dissociates from the Ku complex and releases Ku70/Ku80, which are then recruited
      to DNA DSB sites via the NHEJ DNA repair pathway.

PMID- 24305948
TI  - Urocanate as a potential signaling molecule for bacterial recognition of
      eukaryotic hosts.
AB  - Host recognition is the crucial first step in infectious disease pathogenesis.
      Recognition allows pathogenic bacteria to identify suitable niches and deploy
      appropriate phenotypes for successful colonization and immune evasion. However,
      the mechanisms underlying host recognition remain largely unknown. Mounting
      evidence suggests that urocanate-an intermediate of the histidine degradation
      pathway-accumulates in tissues, such as skin, and acts as a molecule that
      promotes bacterial infection via molecular interaction with the bacterial
      regulatory protein HutC. In Gram-negative bacteria, HutC has long been known as a
      transcriptional repressor of hut genes for the utilization of histidine (and
      urocanate) as sources of carbon and nitrogen. Recent work on the opportunistic
      human pathogen Pseudomonas aeruginosa and zoonotic pathogen Brucella abortus
      shows that urocanate, in conjunction with HutC, plays a significant role in the
      global control of cellular metabolism, cell motility, and expression of virulence
      factors. We suggest that in addition to being a valuable source of carbon and
      nitrogen, urocanate may be central to the elicitation of bacterial pathogenesis. 

PMID- 24305950
TI  - Detectable thyroglobulin with negative imaging in differentiated thyroid cancer
      patients. What to do with negative anatomical imaging and radioiodine scan?
AB  - In the absence of autoantibodies against thyroglobulin (Tg), Tg measurement
      nowadays is the cornerstone of clinical management of differentiated thyroid
      cancer patients. DTC patients presenting with a positive Tg measurement without
      an anatomical correlate on anatomic imaging provide a management challenge to the
      attending physician. Based on the literature we will provide an overview of the
      most important steps to undertake in such patients and their potential clinical
      consequences. 

PMID- 24305949
TI  - Cellular maintenance of nuclear protein homeostasis.
AB  - The accumulation and aggregation of misfolded proteins is the primary hallmark
      for more than 45 human degenerative diseases. These devastating disorders include
      Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Over
      15 degenerative diseases are associated with the aggregation of misfolded
      proteins specifically in the nucleus of cells. However, how the cell safeguards
      the nucleus from misfolded proteins is not entirely clear. In this review, we
      discuss what is currently known about the cellular mechanisms that maintain
      protein homeostasis in the nucleus and protect the nucleus from misfolded protein
      accumulation and aggregation. In particular, we focus on the chaperones found to
      localize to the nucleus during stress, the ubiquitin-proteasome components
      enriched in the nucleus, the signaling systems that might be present in the
      nucleus to coordinate folding and degradation, and the sites of misfolded protein
      deposition associated with the nucleus. 

PMID- 24305951
TI  - Stability of silk and collagen protein materials in space.
AB  - Collagen and silk materials, in neat forms and as silica composites, were flown
      for 18 months on the International Space Station [Materials International Space
      Station Experiment (MISSE)-6] to assess the impact of space radiation on
      structure and function. As natural biomaterials, the impact of the space
      environment on films of these proteins was investigated to understand fundamental
      changes in structure and function related to the future utility in materials and
      medicine in space environments. About 15% of the film surfaces were etched by
      heavy ionizing particles such as atomic oxygen, the major component of the low
      Earth orbit space environment. Unexpectedly, more than 80% of the silk and
      collagen materials were chemically crosslinked by space radiation. These findings
      are critical for designing next-generation biocompatible materials for contact
      with living systems in space environments, where the effects of heavy ionizing
      particles and other cosmic radiation need to be considered. 

PMID- 24305952
TI  - Reply to commentary on "Anthropometrical differences between suicide and other
      non-natural death circumstances: an autopsy study".

PMID- 24305953
TI  - Inverse association between body mass index and suicide?

PMID- 24305954
TI  - Allelic proportions of 16 STR loci-including the new European Standard Set (ESS)
      loci-in a Swiss population sample.
AB  - Allele frequencies and forensically relevant population statistics of 16 STR
      loci, including the new European Standard Set (ESS) loci, were estimated from 668
      unrelated individuals of Caucasian appearance living in different parts of
      Switzerland. The samples were amplified with a combination of the following three
      kits: AmpFlSTR(r) NGM SElectTM, PowerPlex(r) ESI17 and PowerPlex(r) ESX 17. All
      loci were highly polymorphic and no significant departure from Hardy-Weinberg
      equilibrium and linkage equilibrium was detected after correction for sampling.

PMID- 24305955
TI  - Detecting chirality in molecules by imaging photoelectron circular dichroism.
AB  - In this Perspective we discuss photoelectron circular dichroism (PECD), a
      relatively novel technique that can detect chiral molecules with high
      sensitivity. PECD has an enantiomeric sensitivity of typically 1-10%, which is
      two to three orders of magnitude larger than that of the widely employed
      technique of circular dichroism (CD). In PECD a chiral molecule is photoionized
      with circular polarized light, and the photoelectron angular scattering
      distribution is detected using particle imaging techniques. We present the
      general physical principles of photoelectron circular dichroism and we address
      both single- and multiphoton excitation. PECD has been measured with synchrotron
      radiation in single-photon ionization as well as, very recently, with femtosecond
      laser radiation in multiphoton ionization. We discuss the experimental
      implementation of PECD, focusing on velocity map coincidence imaging where the
      momentum distribution of both the electron and the coincident ion is measured.
      The coincident detection of the mass and momentum of the ion adds very powerful
      mass-correlated information to the PECD measurement of the chiral molecule. We
      illustrate the capabilities and the potential of PECD with various experimental
      examples and introduce computational methods that are able to model
      quantitatively experimental PECD results. We conclude with an outlook on novel
      developments and (analytical) implementations of PECD that may further broaden
      the application of PECD for the sensitive detection of chirality in molecules. 

PMID- 24305957
TI  - Development of a Novel Screening Strategy Designed to Discover a New Class of HIV
      Drugs.
AB  - Current antiretroviral treatments target multiple pathways important for human
      immunodeficiency virus (HIV) multiplication, including viral entry, synthesis and
      integration of the DNA provirus, and the processing of viral polyprotein
      precursors. However, HIV is becoming increasingly resistant to these "combination
      therapies." Recent findings show that inhibition of HIV Gag protein cleavage into
      its two structural proteins, matrix (MA) and capsid (CA), has a devastating
      effect on viral production, revealing a potential new target class for HIV
      treatment. Unlike the widely used HIV protease inhibitors, this new class of
      inhibitor would target the substrate, not the protease enzyme itself. This
      approach offers a distinct advantage in that inhibitors of MA/CA would only need
      to affect a subset of the Gag molecules to disable viral replication. To discover
      MA/CA-specific inhibitors, we constructed a modified MA/CA fusion peptide
      (MA/CADelta) that contains the HIV protease (PR) cleavage site as well as a
      tetracysteine motif for fluorescent labeling. The HIV PR cleavage of MA/CADelta
      can then be monitored via fluorescence polarization (FP). We have adapted this FP
      assay for high-throughput screening and validated it according to industry
      standards using a 384-well plate format. We have currently tested 24,000
      compounds in this assay and here detail the screening methodology and the results
      of this screening campaign. 

PMID- 24305958
TI  - Transplant renal artery stenosis in children: risk factors and outcome after
      endovascular treatment.
AB  - BACKGROUND: Transplant renal artery stenosis (TRAS) is an increasingly recognised
      cause of post-transplant hypertension. METHODS: We retrospectively analysed 216
      paediatric renal recipients transplanted between 2001 and 2011 to assess TRAS
      prevalence and percutaneous transluminal angioplasty (PTA) efficacy. To assess
      risk factors, we compared children with TRAS with a propensity score-matched
      cohort of recipients without TRAS. RESULTS: Of the 216 paediatric patients who
      were transplanted in the study period, 44 were hypertensive (prevalence 20.3 %)
      and ten presented with TRAS (prevalence 4.6 %, median age at transplantation 14
      years, range 6.78-17.36 years). Hypertensive patients without TRAS were
      prescribed one to two anti-hypertensive agents, whereas patients with TRAS
      required one to five medications. In the TRAS group, one recipient presented with
      vascular complications during surgery, and in three patients the graft had
      vascular abnormalities. TRAS was detected by Doppler ultrasonography (US)
      performed due to hypertension in nine of the patients with TRAS, but in the tenth
      case the TRAS was clinically silent and detected by routine Doppler-US screening.
      TRAS diagnosis was refined using angio-computed tomography or angio-magnetic
      resonance imaging. All patients underwent PTA without complications. Significant
      improvement after PTA was observed in the standard deviation scores for blood
      pressure [3.2 +/- 1.4 (pre-PTA) vs. 1.04 +/- 0.8 (post-PTA); p = 0.0006) and
      graft function [creatinine clearance: 69 +/- 17.08 (pre-PTA) vs. 80.7 +/- 21.5
      ml/min/1.73 m(2) (post-PTA); p = 0.006] We observed no significant differences
      between the two cohorts for cold ischaemia time, recipient/donor weight ratio,
      delayed graft function, cytomegalovirus infections and acute rejection episodes.
      CONCLUSIONS: Our study reports a low but significant TRAS prevalence among the
      paediatric patients who were transplanted at our centre in the study period and
      confirms that PTA is an effective and safe therapeutic option in paediatric renal
      transplant recipients. Known risk factors do not appear to be related to the
      development of TRAS.

PMID- 24305959
TI  - Near-infrared spectroscopy as continuous real-time monitoring for kidney graft
      perfusion.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) is a non-invasive technique
      designed to study regional oxygenation (rSO(2)) by measuring the absorption of
      chromophores. This study investigated the role of NIRS in the real-time
      monitoring of kidney graft perfusion for 72 h post-transplantation. METHODS:
      Consecutive children undergoing living related donor (LRD) or deceased donor (DD)
      kidney transplantation (KTP) were prospectively enrolled between April 2010 and
      August 2011. Renal rSO(2) values were registered continuously for 3 days and
      correlated with hourly urine output, serum creatinine, and urinary neutrophil
      gelatinase-associated lipocalin (u-NGAL). RESULTS: Twenty-four children were
      included, 6 underwent LRD and 18 DD KTP. Median age was 12.5 years (interquartile
      range [IQR] 3.5-16.6) and median body weight was 37 kg (IQR 13-49.7). Four
      patients experienced delayed graft function (DGF). Renal Doppler ultrasound
      showed normal vascularization patterns in all children. Median basal renal rSO(2)
      value was 68.8 % (IQR 59.3-76.2), significantly lower than the end-of-period
      result (83.6 %; IQR 79.2-90.4; p < 0.0001). Renal rSO(2) values showed
      significant correlation with serum creatinine (rs = -0.62; p < 0.05) and
      estimated glomerular filtration rate (eGFR) (rs = 0.64; p < 0.05). No correlation
      was shown between rSO(2) and diuresis. Increased rSO(2) was also found in
      patients who experienced DGF. u-NGAL exhibited a trend toward a decrease from
      baseline in both DD and LRD KTPs, with a strong negative correlation with rSO(2).
      CONCLUSIONS: rSO(2) assessed by NIRS strongly correlates with common markers of
      kidney graft function and perfusion, allowing continuous real-time monitoring of
      blood flow in renal grafts.

PMID- 24305960
TI  - Update on transcobalamin deficiency: clinical presentation, treatment and
      outcome.
AB  - Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is
      a rare autosomal recessive disorder usually presenting in early infancy with
      failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or
      agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe
      combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based
      on megaloblastic anemia, elevation of total plasma homocysteine, and blood or
      urine methylmalonic acid. It is confirmed by studying the synthesis of TC in
      cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is
      treatable with supplemental cobalamin, but the optimal type, route and frequency
      of cobalamin administration and long term patient outcomes are unknown. Here we
      present a series of 30 patients with TC deficiency, including an update on
      multiple previously published patients, in order to evaluate the different
      treatment strategies and provide information about long term outcome. Based on
      the data presented, current practice appears to favour treatment of individuals
      with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In
      most cases presented, at least weekly injections (1 mg IM) were necessary to
      ensure optimal treatment. Most centres adjusted the treatment regimen based on
      monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid,
      as well as, clinical status. Finally, continuing IM treatment into adulthood
      appears to be beneficial. 

PMID- 24305961
TI  - Muscle MRI in patients with long-chain fatty acid oxidation disorders.
AB  - INTRODUCTION: Muscle magnetic resonance imaging (MRI) is a useful tool for
      visualizing abnormalities in neuromuscular disorders. The value of muscle MRI has
      not been studied in long-chain fatty acid oxidation (lcFAO) disorders. LcFAO
      disorders may present with metabolic myopathy including episodic rhabdomyolysis.
      OBJECTIVE: To investigate whether lcFAO disorders are associated with muscle MRI
      abnormalities. METHODS: Lower body MRI was performed in 20 patients with lcFAO
      disorders, i.e. three carnitine palmitoyltransferase 2 deficiency (CPT2D), 12
      very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), three mitochondrial
      trifunctional protein deficiency (MTPD) and two isolated long-chain hydroxyacyl
      CoA dehydrogenase deficiency (LCHADD). RESULTS: At the time of MRI, four patients
      had muscle weakness, 14 had muscle pain and 13 were exercise intolerant. Median
      creatine kinase (CK) level of patients at the day of MRI was 398 U/L (range 35
      12,483). T1W and STIR signal intensity (SI) were markedly increased in MTPD
      patients from girdle to lower leg. VLCADD patients showed predominantly proximal
      T1W SI changes, whereas LCHADD patients mostly showed distal T1W SI changes.
      Prominent STIR weighted signal intensity increases of almost all muscle groups
      were observed in patients with VLCADD and LCHADD with very high CK (>11.000)
      levels. CONCLUSIONS AND RELEVANCE: lcFAO disorders are associated with specific
      patterns of increased T1W and STIR signal intensity. These patterns may reflect
      lipid accumulation and inflammation secondary to lcFAO defects and progressive
      muscle damage. Future studies are needed to investigate whether muscle MRI might
      be a useful tool to monitor disease course and to study pathogenesis of lcFAO
      related myopathy.

PMID- 24305962
TI  - Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning
      response in human skin.
AB  - IMPORTANCE: Solar UV irradiation causes photoaging, characterized by
      fragmentation and reduced production of type I collagen fibrils that provide
      strength to skin. Exposure to UV-B irradiation (280-320 nm) causes these changes
      by inducing matrix metalloproteinase 1 and suppressing type I collagen synthesis.
      The role of UV-A irradiation (320-400 nm) in promoting similar molecular
      alterations is less clear yet important to consider because it is 10 to 100 times
      more abundant in natural sunlight than UV-B irradiation and penetrates deeper
      into the dermis than UV-B irradiation. Most (approximately 75%) of solar UV-A
      irradiation is composed of UV-A1 irradiation (340-400 nm), which is also the
      primary component of tanning beds. OBJECTIVE: To evaluate the effects of low
      levels of UV-A1 irradiation, as might be encountered in daily life, on expression
      of matrix metalloproteinase 1 and type I procollagen (the precursor of type I
      collagen). DESIGN, SETTING, AND PARTICIPANTS: In vivo biochemical analyses were
      conducted after UV-A1 irradiation of normal human skin at an academic referral
      center. Participants included 22 healthy individuals without skin disease. MAIN
      OUTCOMES AND MEASURES: Skin pigmentation was measured by a color meter
      (chromometer) under the L* variable (luminescence), which ranges from 0 (black)
      to 100 (white). Gene expression in skin samples was assessed by real-time
      polymerase chain reaction. RESULTS: Lightly pigmented human skin (L* >65) was
      exposed up to 4 times (1 exposure/d) to UV-A1 irradiation at a low dose (20
      J/cm2), mimicking UV-A levels from strong sun exposure lasting approximately 2
      hours. A single exposure to low-dose UV-A1 irradiation darkened skin slightly and
      did not alter matrix metalloproteinase 1 or type I procollagen gene expression.
      With repeated low-dose UV-A1 irradiation, skin darkened incrementally with each
      exposure. Despite this darkening, 2 or more exposures to low-dose UV-A1
      irradiation significantly induced matrix metalloproteinase 1 gene expression,
      which increased progressively with successive exposures. Repeated UV-A1 exposures
      did not suppress type I procollagen expression. CONCLUSIONS AND RELEVANCE: A
      limited number of low-dose UV-A1 exposures, as commonly experienced in daily
      life, potentially promotes photoaging by affecting breakdown, rather than
      synthesis, of collagen. Progressive skin darkening in response to repeated low
      dose UV-A1 exposures in lightly pigmented individuals does not prevent UV-A1
      induced collagenolytic changes. Therefore, for optimal protection against skin
      damage, sunscreen formulations should filter all UV wavelengths, including UV-A1
      irradiation.

PMID- 24305963
TI  - Magnitude and mechanisms of glucose counterregulation following islet
      transplantation in patients with type 1 diabetes suffering from severe
      hypoglycaemic episodes.
AB  - AIMS/HYPOTHESIS: Pancreatic islet transplantation stabilises glycaemic control in
      type 1 diabetes mellitus patients with neuroglycopoenia, despite them not
      achieving insulin independence because of limited graft function. However, the
      extent and underlying metabolic pathways of restored glucose counterregulation
      are unknown. We therefore compared systemic glucose turnover, including lactate
      gluconeogenesis (GN) and muscle glucose uptake, in individuals with type 1
      diabetes who were transplant recipients with partial graft function
      (T1DM/ITx(+)), matched non-transplanted individuals with type 1 diabetes
      (T1DM/ITx(-)) and matched healthy non-diabetic individuals. METHODS: Participants
      (n = 12 in each group) underwent a euglycaemic and a hypoglycaemic (2.5-2.8
      mmol/l) hyperinsulinaemic clamp (0.8 mU kg(-1) min(-1)) in a randomised crossover
      fashion. Systemic and skeletal muscle glucose and lactate kinetics were assessed
      using a combination of isotopic and forearm balance techniques. RESULTS: Whole
      body glucose counterregulation, the difference in glucose infusion rates required
      to maintain the glycaemic goal between the hypoglycaemic and euglycaemic clamps,
      was improved in T1DM/ITx(+) (7.8 +/- 1.3 MUmol kg(-1) min(-1)) compared with
      T1DM/ITx(-) (0.3 +/- 0.9 MUmol kg(-1) min(-1)), but was ~45% lower than in
      controls (14.1 +/- 2.1 MUmol kg(-1) min(-1)). Increased endogenous glucose
      production (EGP) and decreased systemic glucose disposal accounted for 49% and
      39% of glucose counterregulation in T1DM/ITx(+), respectively, compared with 60%
      and 36% in controls. Lactate GN increased in T1DM/ITx(+) (2.7 +/- 0.4 MUmol kg(
      1) min(-1)) and controls (1.7 +/- 0.5 MUmol kg(-1) min(-1)), such that it
      accounted for 70% and 20% of the increased EGP, respectively. Skeletal muscle
      accounted for similar proportions of the decrease in systemic glucose disposal in
      controls (49%) and T1DM/ITx(+) (41%). CONCLUSIONS/INTERPRETATION: Partial islet
      graft function improves hypoglycaemia counterregulation by increasing EGP,
      largely via lactate GN and decreasing systemic glucose disposal. This may explain
      the reduction in severe hypoglycaemic events in T1DM/ITx(+) individuals. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01668485.

PMID- 24305964
TI  - HOMA and Matsuda indices of insulin sensitivity: poor correlation with minimal
      model-based estimates of insulin sensitivity in longitudinal settings.
AB  - AIMS/HYPOTHESIS: Little is known about the performance of surrogates in assessing
      changes in insulin sensitivity over time. This report compared updated HOMA of
      insulin sensitivity (HOMA2-%S) and the Matsuda index from OGTTs with minimal
      model-based estimates of insulin sensitivity (SI) from frequently sampled IVGTTs
      (FSIGTs) in longitudinal settings and cross-sectional settings. METHODS: Two
      longitudinal studies were used: one a natural observational study in which 338
      individuals were followed for a median of 4 years; one a clinical treatment study
      in which 97 individuals received pioglitazone treatment and were followed for 1
      year. Pairs of OGTTs and FSIGTs were performed at baseline and follow-up.
      Correlations were computed. Impact of measurement uncertainty was investigated
      through simulation studies. RESULTS: Correlations between HOMA2-%S and SI from
      baseline or follow-up data were in the range reported previously (0.61-0.69). By
      contrast, correlations for changes over time were only 0.35-0.39. The
      corresponding correlations between the Matsuda index and SI were 0.66-0.72 for
      cross-sectional data and 0.40-0.48 for longitudinal change. Correlations for
      changes were significantly lower than the cross-sectional correlations in both
      studies (p < 0.03). Simulation results demonstrated that the reduced correlations
      for change were not explained by error propagation, supporting a real limitation
      of surrogates to fully capture longitudinal changes in insulin sensitivity.
      CONCLUSIONS/INTERPRETATION: HOMA and Matsuda indices derived from cross-sectional
      data should be used cautiously in assessing longitudinal changes in insulin
      sensitivity.

PMID- 24305965
TI  - Infection-related mortality is higher for kidney allograft recipients with
      pretransplant diabetes mellitus.
AB  - AIMS/HYPOTHESIS: The risk of infection-related mortality in kidney allograft
      recipients with pre-existing diabetes mellitus is unknown. We determined the risk
      of infection-related mortality after kidney transplantation in a population-based
      cohort stratified by diagnosis of pre-existing diabetes mellitus. METHODS: We
      linked data between two national registries (Hospital Episode Statistics and the
      Office for National Statistics) to select all mortality events after kidney
      transplantation in England between April 2001 and March 2012. The primary outcome
      measure was infection-related mortality after transplantation comparing diabetic
      with non-diabetic recipients. RESULTS: A total of 19,103 kidney allograft
      recipients were analysed; 2,968 (15.5%) were known to have diabetes before kidney
      transplantation. After transplantation, 2,085 deaths (10.9%) occurred (median
      follow-up 4.4 years [interquartile range 2.2-7.3]), with 434 classified as
      secondary to infection (20.8% of all deaths). Risk of overall (16.0% vs 10.0%, p
      < 0.001) and infection-related (3.3% vs 2.1%, p < 0.001) mortality after kidney
      transplantation was higher for diabetic than non-diabetic recipients,
      respectively. No cytomegalovirus-related deaths occurred in diabetic recipients
      compared with 5.7% in non-diabetic recipients (p < 0.007), with a trend towards
      more unspecified sepsis in diabetic recipients (30.6% vs 22.6%, respectively, p =
      0.070). Diabetes at the time of transplantation was an independent risk factor
      predicting infection-related mortality in kidney allograft recipients after
      transplantation (HR 1.71 [95% CI 1.36, 2.15], p < 0.001).
      CONCLUSIONS/INTERPRETATION: Infection-related mortality is more common in kidney
      allograft recipients with pre-existing diabetes mellitus. Further work is
      required to determine whether attenuated immunosuppression is beneficial for
      diabetic kidney allograft recipients.

PMID- 24305966
TI  - Matrix metalloproteinase 9 opposes diet-induced muscle insulin resistance in
      mice.
AB  - AIMS/HYPOTHESIS: Increased extracellular matrix (ECM) collagen is a
      characteristic of muscle insulin resistance. Matrix metalloproteinase (MMP) 9 is
      a primary enzyme that degrades collagen IV (ColIV). As a component of the
      basement membrane, ColIV plays a key role in ECM remodelling. We tested the
      hypotheses that genetic deletion of MMP9 in mice increases muscle ColIV, induces
      insulin resistance in lean mice and worsens diet-induced muscle insulin
      resistance. METHODS: Wild-type (Mmp9(+/+)) and Mmp9-null (Mmp9(-/-)) mice were
      chow or high-fat (HF) fed for 16 weeks. Insulin action was measured by the
      hyperinsulinaemic-euglycaemic clamp in conscious weight-matched surgically
      catheterised mice. RESULTS: Mmp9(-/-) and HF feeding independently increased
      muscle ColIV. ColIV in HF-fed Mmp9(-/-) mice was further increased. Mmp9(-/-) did
      not affect fasting insulin or glucose in chow- or HF-fed mice. The glucose
      infusion rate (GIR), endogenous glucose appearance (EndoRa) and glucose
      disappearance (Rd) rates, and a muscle glucose metabolic index (Rg), were the
      same in chow-fed Mmp9(+/+) and Mmp9(-/-) mice. In contrast, HF-fed Mmp9(-/-) mice
      had decreased GIR, insulin-stimulated increase in Rd and muscle Rg. Insulin
      stimulated suppression of EndoRa, however, remained the same in HF-fed Mmp9(-/-)
      and Mmp9(+/+) mice. Decreased muscle Rg in HF-fed Mmp9(-/-) was associated with
      decreased muscle capillaries. CONCLUSIONS/INTERPRETATION: Despite increased
      muscle ColIV, genetic deletion of MMP9 does not induce insulin resistance in lean
      mice. In contrast, this deletion results in a more profound state of insulin
      resistance, specifically in the skeletal muscle of HF-fed mice. These results
      highlight the importance of ECM remodelling in determining muscle insulin
      resistance in the presence of HF diet.

PMID- 24305967
TI  - Inflorescence dimorphism, heterodichogamy and thrips pollination in Platycarya
      strobilacea (Juglandaceae).
AB  - BACKGROUND AND AIMS: Unlike other taxa in Juglandaceae or in closely related
      families, which are anemophilous, Platycarya strobilacea has been suggested to be
      entomophilous. In Juglandaceae, Juglans and Carya show heterodichogamy, a
      reproductive strategy in which two morphs coexist in a population and undergo
      synchronous reciprocal sex changes. However, there has been no study focusing on
      heterodichogamy in the other six or seven genera, including Platycarya. METHODS:
      Inflorescence architecture, sexual expression and pollination biology were
      examined in a P. strobilacea population in Japan. Flowering phenology was
      monitored daily for 24 trees in 2008 and 27 in 2009. Flower visitors and
      inhabitants were recorded or collected from different sexes and stages. KEY
      RESULTS: The population of P. strobilacea showed heterodichogamous phenology with
      protogynous and duodichogamous-protandrous morphs. This dimorphism in dichogamy
      was associated with distinct inflorescence morphologies. Thrips pollination was
      suggested by the frequent presence of thrips with attached pollen grains, the
      scarcity of other insect visitors, the synchronicity of thrips number in male
      spikes with the maturation of female flowers, and morphological characters shared
      with previously reported thrips-pollinated plants. Male spikes went through two
      consecutive stages: bright yellow and strong-scented M1 stage, and brownish and
      little-scented M2 stage. The latter contained more thrips, synchronized better
      with the receptive stage of female flowers of the reciprocal morph and is
      probably the main period of pollen export. CONCLUSIONS: Platycarya strobilacea is
      heterodichogamous and thrips-pollinated, both of which are relatively rare
      conditions in angiosperms. In male spikes of P. strobilacea, there is probably a
      temporal decoupling of pollinator attraction and pollen export.

PMID- 24305968
TI  - Sex pheromone of fall armyworm,Spodoptera frugiperda (J.E. Smith) :
      Identification of components critical to attraction in the field.
AB  - Analyses of extracts of pheromone glands and of volatiles from calling female
      fall armyworm moths,Spodoptera frugiperda (J.E. Smith), revealed the presence of
      the following compounds: dodecan-1-ol acetate, (Z)-7-dodecen-1-ol acetate, 11
      dodecen-1-ol acetate, (Z)-9-tetradecenal, (Z)-9-tetradecen-1-ol acetate, (Z)-11
      hexadecenal, and (Z)-11-hexadecen-1-ol acetate. The volatiles emitted by calling
      females differed from the gland extract in that the two aldehydes were absent.
      Field tests were conducted with sticky traps baited with rubber septa formulated
      to release blends with the same component ratios as those emitted by calling
      females. These tests demonstrated that both (Z)-7-dodecen-1-ol acetate and (Z)-9
      tetradecen-1-ol acetate are required for optimum activity and that this blend is
      a significantly better lure than either virgin females or 25 mg of (Z)-9-dodecen
      1-ol acetate in a polyethylene vial, the previously used standard. Addition of
      the other three acetates found in the volatiles did not significantly increase
      the effectiveness of the two-component blend as a bait for Pherocon 1C or
      International Pheromones moth traps. 

PMID- 24305969
TI  - Odor mimetism? : Key substances inOphrys lutea-Andrena pollination relationship
      (Orchidaceae: Andrenidae).
AB  - The hypothesis of chemical mimesis in the relationship betweenOphrys orchids and
      their pollinators was tested experimentally using preparations ofOphrys lutea
      var.lutea odor and the males of the solitary beeAndrena fuscipes, a species
      constellation that does not coexist under natural conditions. Correspondence in
      odor production was shown to occur. Identification of the compounds in the
      cephalic secretion ofA. fuscipes, males and females, and the flower labella
      extracts, was performed by gas chromatography and mass spectrometry. Geraniol,
      nerol, citral,E,E-farnesol and 6-methyl-5-hepten-2-one were present in the
      extracts of both the orchid and one or both sexes of the bee. Extracts, TLC
      fractions of extracts, blends, and separate compounds were tested in the field in
      the mating flight areas ofA. fuscipes males. Extracts and blends containingE,E
      farnesol, geraniol, and geranial showed the highest attractivity to the male
      bees. These compounds seem to be responsible for the release of the odor-guided
      mating behavior at theO. lutea labellum and can be regarded as general
      attractants for many species ofAndrena. 

PMID- 24305970
TI  - Female-produced sexual pheromone ofSceliodes cordalis (Lepidoptera: Pyralidae).
AB  - (E)-11-Hexadecen-1-yl acetate and (E)-11-hexadecen-1-ol were identified in
      extracts from the abdominal pheromone gland of femaleSceliodes cordalis and in a
      1?1 ratio acted as a potent field attractant for males. Sustained upwind flight
      by males to this mixture in a wind tunnel confirmed the identity of these
      compounds as major components of the natural sex pheromone of this species. The
      synthetic pheromone was used to define the annual limits of male flight activity.
      In the presence of 1-10 MUg of pheromone per liter of air, the mating rate of
      laboratory populations was halved. TheZ isomers of both pheromone components
      decreased the numbers of males captured in traps baited with virgin females in
      the field and inhibited upwind flight in the wind tunnel. The attraction of males
      ofMnesictena flavidalis to virgin females ofS. cordalis and synthetic mixtures
      was demonstrated to be due to the acetate component alone. MaleEudonia sp.
      nrlinealis were captured by (Z)-11-hexadecen-1-yl acetate. 

PMID- 24305972
TI  - Scale esterase: A pheromone-degrading enzyme from scales of silk mothAntheraea
      polyphemus.

PMID- 24305971
TI  - Nestmate recognition cues in laboratory and field colonies ofSolenopsis invicta
      buren (Hymenoptera: Formicidae) : Effect of environment and role of cuticular
      hydrocarbons.
AB  - Laboratory-rearedSolenopsis invicta workers were tested for the ability to
      discriminate nestmates from nonnestmate conspecifics. Postcontact aggressive
      response to workers from local field colonies was significantly greater than the
      response to lab-reared workers, even when the latter were selected from colonies
      originating hundreds of miles away. Behavioral observations support the
      conclusion that lab-reared ants were less distinctive than field-collected ants
      with respect to recognition cues detectable on the cuticle. Potential
      environmental factors affecting colony odor are discussed. In addition, gas
      liquid Chromatographic and statistical analyses of the majorS. invicta cuticular
      hydrocarbons indicate that cuticular hydrocarbon pattern was a poor predictor of
      laboratory colony response to field colony workers. 

PMID- 24305973
TI  - Lespedeza Phenolics andPenstemon alkaloids: Effects on digestion efficiencies and
      growth of voles.

PMID- 24305974
TI  - Female sex as an independent risk factor for stroke in atrial fibrillation:
      possible mechanisms.
AB  - Atrial fibrillation (AF) is an independent risk factor for thromboembolism and
      stroke. Women with AF are at a higher overall risk for thromboembolic stroke when
      compared to men with AF. Recent evidence suggests that female sex, after
      adjusting for stroke risk profile and sex differences in utilisation of
      anticoagulation, is an independent stroke risk factor in AF. The inclusion of
      female sex has improved the accuracy of the CHADS2 stroke risk stratification
      schema (Congestive heart failure, Hypertension, Age 75 years or greater, Diabetes
      mellitus, and prior Stroke or TIA). The newly revised and validated schema,
      CHA2DS2-VASc, dichotomises age and incorporates female sex and vascular disease
      history. The pathophysiological mechanisms to explain this increased risk in
      women are not well understood. According to Virchow's triad, thrombosis that
      leads to stroke in AF should arise from three co-existing phenomena: structural
      abnormalities, blood stasis, and a hypercoagulable state. Herein, we explore the
      sex differences in the biological processes that lead to thrombus formation as
      applied to Virchow's Triad. The objective of this review is to describe the
      potential mechanisms behind the increased risk of stroke in AF associated with
      female sex. 

PMID- 24305975
TI  - Teamwork matters: coordinated neuronal activity in brain systems relevant to
      psychiatric disorders.

PMID- 24305976
TI  - Does shear wave ultrasound independently predict axillary lymph node metastasis
      in women with invasive breast cancer?
AB  - Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound
      examination in assessing breast masses. In breast cancer, higher lesion stiffness
      on SWE has been shown to be associated with features of poor prognosis. The
      purpose of this study was to assess whether lesion stiffness at SWE is an
      independent predictor of lymph node involvement. Patients with invasive breast
      cancer treated by primary surgery, who had undergone SWE examination were
      eligible. Data were retrospectively analysed from 396 consecutive patients. The
      mean stiffness values were obtained using the Aixplorer(r) ultrasound machine
      from SuperSonic Imagine Ltd. Measurements were taken from a region of interest
      positioned over the stiffest part of the abnormality. The average of the mean
      stiffness value obtained from each of two orthogonal image planes was used for
      analysis. Associations between lymph node involvement and mean lesion stiffness,
      invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status
      and vascular invasion were assessed using univariate and multivariate logistic
      regression. At univariate analysis, invasive size, histologic grade, HER-2
      status, vascular invasion, tumour type and mean stiffness were significantly
      associated with nodal involvement. Nodal involvement rates ranged from 7 % for
      tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of
      >150 kPa. At multivariate analysis, invasive size, tumour type, vascular
      invasion, and mean stiffness maintained independent significance. Mean stiffness
      at SWE is an independent predictor of lymph node metastasis and thus can confer
      prognostic information additional to that provided by conventional preoperative
      tumour assessment and staging.

PMID- 24305977
TI  - Histone deacetylase inhibitor entinostat reverses epithelial to mesenchymal
      transition of breast cancer cells by reversing the repression of E-cadherin.
AB  - Loss of ERalpha in breast cancer correlates with poor prognosis, increased
      recurrence rates, and higher incidence of metastasis. Epigenetic silencing of E
      cadherin (loss of which is associated with more invasive phenotype) is observed
      in metastatic cell lines and invasive breast cancers. Here, we are showing that
      entinostat (ENT) can reverse epithelial to mesenchymal transition (EMT), which is
      considered to be a first step in the process of metastases formation. Triple
      negative breast cancer cells such as MDA-MB-231 and Hs578T show a basal phenotype
      characterized by loss of E-cadherin expression and higher expression of
      mesenchymal markers such as N-cadherin and vimentin along with transcriptional
      repressors such as twist and snail. When MDA-MB-231 and Hs578T cells or tumors
      were treated with ENT, E-cadherin transcription was increased along with
      reduction in N-cadherin mRNA expression. Chromatin immunoprecipitation assay
      showed that treatment of MDA-MB-231 and Hs578T cells increased the activation of
      E-cadherin promoter by reducing the association of twist and snail with the E
      cadherin (CDH1) promoter and downregulated both the snail and twist. ENT also
      inhibited cell migration in vitro. In addition, phosphorylation of vimentin was
      increased, as well as remodeling of vimentin filaments. ENT treatment also
      reduced formation of tubulin-based microtentacles, which help floating cells
      attach to other surfaces. These findings suggest that ENT can reverse EMT and may
      reduce the formation of metastasis. 

PMID- 24305978
TI  - Preoperative breast MRI and surgical outcomes in elderly women with invasive
      ductal and lobular carcinoma: a population-based study.
AB  - Existing evidence suggests that preoperative breast magnetic resonance imaging
      (MRI) might not improve surgical outcomes in the general breast cancer
      population. To determine if patients differentially benefit from breast MRI, we
      examined surgical outcomes-initial mastectomy, reoperation, and final mastectomy
      rates-among patients grouped by histologic type. We identified women diagnosed
      with early-stage breast cancer from 2004 to 2007 in the SEER-Medicare dataset. We
      classified patients as having invasive ductal carcinoma (IDC), invasive lobular
      carcinoma (ILC), mixed ductal/lobular carcinoma (IDLC) or other histologic type.
      Medicare claims were used to identify breast MRI and definitive surgeries during
      the initial surgical treatment episode. We used propensity score methods to
      account for the differential likelihood of exposure to MRI. Of the 20,332
      patients who met our inclusion criteria for this study, 12.2 % had a preoperative
      breast MRI. Patients with ILC as compared to other histologic groups were most
      likely to receive MRI [OR 2.32; 95 % CI (2.02-2.67)]. In the propensity score
      adjusted analyses, breast MRI was associated with an increased likelihood of an
      initial mastectomy for all patients and among all histologic subgroups. Among
      patients with ILC, having a breast MRI was associated with lower odds of a
      reoperation [OR 0.59; 95 % CI (0.40-0.86)], and an equal likelihood of a final
      mastectomy compared to similar patients without a breast MRI. Overall and among
      patients with IDC and IDLC, breast MRI was not significantly associated with a
      likelihood of a reoperation but was associated with greater odds of a final
      mastectomy. Our study provides evidence in support of the targeted use of
      preoperative breast MRI among patients with ILC to improve surgical planning; it
      does not provide evidence for the routine use of breast MRI among all newly
      diagnosed breast cancer patients or among patients with IDC. 

PMID- 24305979
TI  - Symptoms of endocrine treatment and outcome in the BIG 1-98 study.
AB  - There may be a relationship between the incidence of vasomotor and
      arthralgia/myalgia symptoms and treatment outcomes for postmenopausal breast
      cancer patients with endocrine-responsive disease who received adjuvant letrozole
      or tamoxifen. Data on patients randomized into the monotherapy arms of the BIG 1
      98 clinical trial who did not have either vasomotor or arthralgia/myalgia/carpal
      tunnel (AMC) symptoms reported at baseline, started protocol treatment and were
      alive and disease-free at the 3-month landmark (n = 4,798) and at the 12-month
      landmark (n = 4,682) were used for this report. Cohorts of patients with
      vasomotor symptoms, AMC symptoms, neither, or both were defined at both 3 and 12
      months from randomization. Landmark analyses were performed for disease-free
      survival (DFS) and for breast cancer free interval (BCFI), using regression
      analysis to estimate hazard ratios (HR) and 95 % confidence intervals (CI).
      Median follow-up was 7.0 years. Reporting of AMC symptoms was associated with
      better outcome for both the 3- and 12-month landmark analyses [e.g., 12-month
      landmark, HR (95 % CI) for DFS = 0.65 (0.49-0.87), and for BCFI = 0.70 (0.49
      0.99)]. By contrast, reporting of vasomotor symptoms was less clearly associated
      with DFS [12-month DFS HR (95 % CI) = 0.82 (0.70-0.96)] and BCFI (12-month DFS HR
      (95 % CI) = 0.97 (0.80-1.18). Interaction tests indicated no effect of treatment
      group on associations between symptoms and outcomes. While reporting of AMC
      symptoms was clearly associated with better DFS and BCFI, the association between
      vasomotor symptoms and outcome was less clear, especially with respect to breast
      cancer-related events. 

PMID- 24305980
TI  - Genomic copy number imbalances associated with bone and non-bone metastasis of
      early-stage breast cancer.
AB  - The aim of this study is to identify and validate copy number aberrations in
      early-stage primary breast tumors associated with bone or non-bone metastasis.
      Whole-genome molecular inversion probe arrays were used to evaluate copy number
      imbalances (CNIs) in breast tumors from 960 early-stage patients with information
      about site of metastasis. The CoxBoost algorithm was used to select metastasis
      site-related CNIs and to fit a Cox proportional hazards model. Gains at 1q41 and
      1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with
      bone metastasis. Gains at 2p11.2, 3q21.3-22.2, 3q27.1, 10q23.1, and 14q13.2-3 and
      loss at 7q21.11 were associated with non-bone metastasis. To examine the joint
      effect of CNIs and clinical predictors, patients were stratified into three risk
      groups (low, intermediate, and high) based on the sum of predicted linear hazard
      ratios. For bone metastasis, the hazard (95 % confidence interval) for the low
      risk group was 0.32 (0.11-0.92) compared to the intermediate-risk group and 2.99
      (1.74-5.11) for the high-risk group. For non-bone metastasis, the hazard for the
      low-risk group was 0.34 (0.17-0.66) and 2.33 (1.59-3.43) for the high-risk group.
      The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for
      non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases
      were externally validated in 335 breast tumors pooled from four independent
      cohorts. Distinct CNIs are independently associated with bone and non-bone
      metastasis for early-stage breast cancer patients across cohorts. These data
      warrant consideration for tailoring surveillance and management of metastasis
      risk. 

PMID- 24305981
TI  - Comparison of embolic agents used in uterine artery embolisation: a systematic
      review and meta-analysis.
AB  - PURPOSE: This study was designed to undertake systematic review and meta-analysis
      of published comparative trials comparing embolic agents used in uterine artery
      embolisation (UAE) for uterine leiomyomata. METHODS: Systematic literature
      searches were performed in MEDLINE, Embase, PubMed, and Cochrane Central
      databases from database inception to July 2012. Randomised and nonrandomised
      trials comparing two or more embolic agents used in UAE were included. Assessment
      included five widely used embolic agents: nonspherical polyvinyl alcohol (PVA)
      (Contour PVA, Boston Scientific or PVA Cook Medical); spherical PVA (Contour SE,
      Boston Scientific); acrylamido PVA (Beadblock, Biocompatibles, Terumo); tris
      acryl gelatin microspheres (TAGM) (Embospheres, Merit Medical Inc); and polyzene
      F hydrogel microspheres (Embozenes, CeloNova Biosciences). Outcomes assessed
      included: quality of life (QOL), assessment, magnetic resonance imaging (MRI),
      uterine and fibroid volumes and degrees of MRI fibroid enhancement and
      devascularisation. A total of 262 citations were reviewed with 5 randomised,
      controlled trials involving 295 women and 5 non-RCTs involving 617 women
      included. RESULTS: No evidence of superiority of any embolic agent was
      demonstrated. Meta-analysis was performed between TAGM (Embospheres) and
      spherical PVA microspheres. Two RCTs found a trend toward greater uterine and
      dominant fibroid volume reductions with Embospheres but the combined differences
      were not statistically significant (p = 0.78 and p = 0.94 respectively).
      Embospheres demonstrated greater percentage fibroid devascularisation than
      spherical PVA (p = 0.039). CONCLUSIONS: This study confirms that the current
      evidence demonstrates superiority of Embospheres over spherical PVA but no
      reported differences in outcomes between any of the other agents. Comparison of
      embolic agents was limited by lack of RCT data and further research is warranted.

PMID- 24305982
TI  - Chemical renal denervation in the rat.
AB  - INTRODUCTION: The recent success of renal denervation in lowering blood pressure
      in drug-resistant hypertensive patients has stimulated interest in developing
      novel approaches to renal denervation including local drug/chemical delivery. The
      purpose of this study was to develop a rat model in which depletion of renal
      norepinephrine (NE) could be used to determine the efficacy of renal denervation
      after the delivery of a chemical to the periadventitial space of the renal
      artery. METHODS: Renal denervation was performed on a single renal artery of 90
      rats (n = 6 rats/group). The first study determined the time course of renal
      denervation after surgical stripping of a renal artery plus the topical
      application of phenol in alcohol. The second study determined the efficacy of
      periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid.
      The final study determined the dose-response relationship for paclitaxel. In all
      studies, renal NE content was determined by liquid chromatography-mass
      spectrometry. RESULTS: Renal NE was depleted 3 and 7 days after surgical
      denervation. Renal NE was also depleted by periadventitial delivery of all agents
      tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose
      response was observed after the application of 150 MUL of 10(-5) M through 10(-2)
      M paclitaxel. CONCLUSION: We developed a rat model in which depletion of renal NE
      was used to determine the efficacy of renal denervation after perivascular renal
      artery drug/chemical delivery. We validated this model by demonstrating the
      efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and
      guanethidine and increasing doses of paclitaxel.

PMID- 24305983
TI  - In memory of Dr. Hideo Uchida.

PMID- 24305984
TI  - Pancreas transplants venous graft thrombosis: endovascular thrombolysis for graft
      rescue.
AB  - PURPOSE: To retrospectively assess the efficacy and safety of percutaneous
      endovascular treatment in patients with pancreas venous graft thrombosis (PVGT).
      MATERIALS AND METHODS: Between 2001 and 2009, 206 pancreas transplants were
      performed at our institution. A retrospective review of pancreas graft recipients
      who underwent endovascular therapy for PVGT was performed. The study group
      included 17 patients (10 men, 7 women; mean age 38 years) with PVGT (<60 % [9
      patients]; 30-60 % [8 patients]) 6.6 +/- 5.7 days after grafting. The
      angiographic studies, type of endovascular procedure, endovascular procedural and
      postprocedural effectiveness, and patient and graft outcomes were assessed.
      RESULTS: In 16 of 17 cases (94 %), significant (87.5 %) or partial (12.5 %) lysis
      of thrombi was achieved. One patient had external compression of the portal vein
      due to a hematoma, which hindered mechanical removal of the thrombi. This patient
      required graft pancreatectomy for extensive areas of parenchymal necrosis 2 days
      after the endovascular procedure. No complications related to endovascular
      treatment were observed. Postprocedural bleeding episodes related to
      anticoagulation were observed in five patients. Patient and pancreas graft
      survival rates at 12 months were 94 and 76 %, respectively. CONCLUSION: Catheter
      directed thrombectomy is an effective treatment for patients with PVGT.
      Percutaneous thrombectomy, followed by anticoagulation, appears to be an
      effective therapy to remove the thrombus and is associated with a low
      complication rate.

PMID- 24305985
TI  - Endovascular aneurysm sealing for abdominal aortic aneurysm repair: evolution or
      revolution?

PMID- 24305986
TI  - Aggressive vertebral hemangioma treated with combination of vertebroplasty and
      sclerotherapy through transpedicular and direct approach.

PMID- 24305987
TI  - Upside down use of Gore Excluder or Cook Zenith legs.
AB  - PURPOSE: Endovascular aneurysm repair is becoming increasingly popular. This
      technical note describes the usefulness of the upside-down technique of Gore
      Excluder or Cook Zenith legs. METHODS: Four patients with iliac or abdominal
      aortic aneurysms were treated. Three patients with isolated iliac artery
      aneurysms and one patient with an abdominal aortic aneurysm, in which the neck
      diameters were unfit for commercially available stent-grafts, were treated using
      an Excluder or a Zenith leg in an upside-down technique. RESULTS: The aneurysms
      were completely excluded and no endoleak occurred. There were no serious adverse
      events. CONCLUSIONS: The upside-down technique using an Excluder leg or a Zenith
      leg is both feasible and effective.

PMID- 24305988
TI  - Recurrent cerebral hyperperfusion syndrome after intracranial angioplasty and
      stenting: case report with review of literature.
AB  - Cerebral hyperperfusion syndrome (CHS) describes a syndrome of sudden onset focal
      neurological features, unilateral headache, and systemic hypertension. Recurrent
      CHS in the same patient has not been described to date. We describe a 55-year-old
      woman who first developed CHS post intracranial stenting with sudden-onset right
      focal seizures and associated acute focal edema on imaging. After one and half
      years, the patient developed symptomatic in-stent restenosis and underwent repeat
      angioplasty with stenting. Postprocedure, the patient had another episode of CHS
      in the form of acute bleed in the basal ganglia and died. A review of literature
      of patients for CHS postintracranial angioplasty and stenting also was performed.
      The present case describes a rare clinical scenario where the patient had
      recurrent CHS with different clinical and imaging features. 

PMID- 24305989
TI  - Active anti-erosion protection strategy in tamarisk (Tamarix aphylla).
AB  - Plants have numerous active protection strategies for adapting to complex and
      severe environments. These strategies provide endless inspiration for extending
      the service life of materials and machines. Tamarisk (Tamarix aphylla), a tree
      that thrives in raging sandstorm regions, has adapted to blustery conditions by
      evolving extremely effective and robust erosion resistant characteristics.
      However, the relationships among its surface cracks, internal histology and
      biomechanics, such as cracks, rings, cells, elasticity modulus and growth stress,
      which account for its erosion resistance, remain unclear. This present study
      reveals that the directionally eccentric growth rings of tamarisk, which are
      attributed to reduced stress and accelerated cell division, promote the formation
      of surface cracks. The windward rings are more extensive than the leeward side
      rings. The windward surfaces are more prone to cracks, which improves erosion
      resistance. Our data provide insight into the active protection strategy of the
      tamarisk against wind-sand erosion. 

PMID- 24305991
TI  - Oxidative degradation of silica-supported polyethylenimine for CO2 adsorption:
      insights into the nature of deactivated species.
AB  - The oxidative degradation of polyethylenimine-impregnated mesoporous SBA-15
      silica for CO2 capture was investigated at the molecular level. The adsorbents
      were exposed to flowing air at different temperatures, and their degree of
      deactivation was evaluated through the measurement of CO2 adsorption capacity
      prior and subsequent to air exposure. A solvent-extraction method was employed to
      isolate the deactivated species from the silica support. The extracted species
      were investigated by a variety of 1D and 2D NMR techniques such as (13)C, (1)H,
      (1)H-(15)N HMBC, (1)H-(13)C HMQC, and (1)H-(13)C HMBC. This in-depth
      investigation showed that they contain predominantly fragments involving imine
      and carbonyl groups. Several structural units were conclusively established. 

PMID- 24305990
TI  - Differential MMP-9 activity in CD34+progenitor cell-derived foam cells from
      diabetic and normoglycemic patients.
AB  - BACKGROUND: Upon coincubation with platelet aggregates, CD34(+) progenitor cells
      have the potential to differentiate into foam cells. There is evidence that
      progenitor cells from diabetic and nondiabetic patients have different
      properties, which may affect the patients' prognosis. In this study we
      investigated an in vitro model of foam cell formation based on patient-derived
      CD34(+) progenitor cells. We analyzed the growth characteristics as well as the M
      CSF-release and matrix metalloproteinase (MMP) synthesis from CD34(+) progenitor
      cell-derived foam cells originating from diabetic and nondiabetic patients.
      METHODS AND RESULTS: Bone marrow samples were obtained from 38 patients who were
      elected for thoracic surgery. CD34(+) progenitor cells from diabetic and
      nondiabetic patients were isolated and incubated with platelets from healthy
      volunteers. Foam cell formation was confirmed by immunostaining (CD68) and
      quantified by light microscopy. Whereas the absolute number of foam cells was not
      affected, the negative slope in the growth curve was seen significantly later in
      the diabetic group. In supernatants derived from"diabetic" CD34(+) progenitor
      cells, MMP-9 was significantly enhanced, whereas MMP-2 activity or M-CSF-release
      was not affected significantly. CONCLUSION: In a coculture model of CD34(+)
      progenitor cells with platelets, we show for the first time that"diabetic"
      CD34(+) progenitor cells exhibit functional differences in their differentiation
      to foam cells concerning growth characteristics and release of MMP-9.

PMID- 24305992
TI  - Prediction of mean skin temperature for use as a heat strain scale by introducing
      an equation for sweating efficiency.
AB  - The present paper made the heat balance equation (HBE) for nude or minimally clad
      subjects a linear function of mean skin temperature (t(sk)) by applying new
      equations for sweating efficiency (eta(sw)) and thermoregulatory sweat rate
      (S(wR)). As the solution of the HBE, the equation predicting t(sk) was derived
      and used for a heat strain scale of subjects. The eta(sw) was proportional to the
      reciprocal of S(w)/E(max) (S(w), sweat rate; E(max) maximum evaporative capacity)
      and the S(wR) was proportional to t(sk) with a parameter of the sweating capacity
      of the subject. The errors of predicted t(sk) from observations due to the
      approximation of eta(sw) were examined based on experimental data conducted on
      eight young male subjects. The value of errors of t(sk) was -0.10 +/- 0.42 
      degrees C (mean +/- sample standard deviation (SSD)). We aim to apply the
      predicted t(sk) of a subject at a level of sweating capacity as a heat strain
      scale of a function of four environmental factors (dry- and wet-bulb
      temperatures, radiation, and air velocity) and three human factors (metabolic
      rate, sweating capacity, and clothing (<=0.2clo)).

PMID- 24305993
TI  - Gait and upper limb variability in Parkinson's disease patients with and without
      freezing of gait.
AB  - Patients with Parkinson's disease (PD) and freezing of gait (FOG) (freezers)
      demonstrate high gait variability. The objective of this study was to determine
      whether freezers display a higher variability of upper limb movements and
      elucidate if these changes correlate with gait. We were the first group to
      compare directly objectively measured gait and upper limb movement variability of
      freezers between freezing episodes. Patients with objectively verified FOG (n =
      11) and PD patients without FOG (non-freezers) (n = 11) in a non-randomized
      medication condition (OFF/ON) were analyzed. Uncued antiphasic finger tapping and
      forearm diadochokinetic movements were analyzed via three-dimensional ultrasound
      kinematic measurements. Gait variability of straight gait was assessed using
      ground reaction forces. Freezers had shorter stride length (p = 0.004) and higher
      stride length variability (p = 0.005) in the medication OFF condition. Movement
      variability was not different during finger tapping or diadochokinesia between
      the groups. There was a trend towards more freezing of the upper limb during
      finger tapping for the freezers (p = 0.07). Variability in stride length
      generation and stride timing was not associated with variability of upper limb
      movement in freezers. Our findings demonstrate that: (1) freezers have a higher
      spatial gait variability between freezing episodes; (2) freezing-like episodes of
      the upper limb occur in PD patients, and tend to be more pronounced among
      freezers than non-freezers for finger tapping; (3) spatial and temporal upper
      extremity variability is equally affected in freezers and non-freezers in an
      uncued task. Upper limb freezing is not correlated to lower limb freezing,
      implicating a different pathophysiology. 

PMID- 24305994
TI  - Structural brain MRI abnormalities in pediatric patients with migraine.
AB  - Morphometric MRI studies in adult patients with migraine have consistently
      demonstrated atrophy of several gray matter (GM) regions involved in pain
      processing. We explored the regional distribution of GM and white matter (WM)
      abnormalities in pediatric patients with episodic migraine and their correlations
      with disease clinical manifestations. Using a 3.0 T scanner, brain T2-weighted
      and 3D T1-weighted scans were acquired from 12 pediatric migraine patients and 15
      age-matched healthy controls. GM and WM volumetric abnormalities were estimated
      using voxel-based morphometry (p < 0.05, family-wise error corrected). Compared
      to controls, pediatric migraine patients experienced a significant GM atrophy of
      several regions of the frontal and temporal lobes which are part of the pain
      processing network. They also had an increased volume of the right putamen. The
      left fusiform gyrus had an increased volume in patients with aura compared to
      patients without aura and controls, whereas it was significantly atrophied in
      patients without aura when compared to the other two groups. No abnormalities of
      WM volume were detected. In migraine patients, regional GM atrophy was not
      correlated with disease duration and attack frequency, whereas a negative
      correlation was found between increased volume of the putamen and disease
      duration (r = -0.95, p < 0.05). These results show that GM morphometric
      abnormalities do occur in pediatric patients with migraine. The presence of such
      abnormalities early in the disease course, and the absence of correlation with
      patient clinical characteristics suggest that they may represent a phenotypic
      biomarker of this condition. 

PMID- 24305995
TI  - Are Caribbean reef sharks, Carcharhinus perezi, able to perceive human body
      orientation?
AB  - The present study examines the potential capability of Caribbean reef sharks to
      perceive human body orientation, as well as discussing the sharks' swimming
      patterns in a person's vicinity. A standardized video method was used to record
      the scenario of single SCUBA divers kneeling in the sand and the approach
      patterns of sharks, combined with a control group of two divers kneeling back-to
      back. When approaching a single test-subject, significantly more sharks preferred
      to swim outside the person's field of vision. The results suggest that these
      sharks are able to identify human body orientation, but the mechanisms used and
      factors affecting nearest distance of approach remain unclear.

PMID- 24305996
TI  - How dogs scan familiar and inverted faces: an eye movement study.
AB  - Faces play an important role in communication and identity recognition in social
      animals. Domestic dogs often respond to human facial cues, but their face
      processing is weakly understood. In this study, facial inversion effect (deficits
      in face processing when the image is turned upside down) and responses to
      personal familiarity were tested using eye movement tracking. A total of 23 pet
      dogs and eight kennel dogs were compared to establish the effects of life
      experiences on their scanning behavior. All dogs preferred conspecific faces and
      showed great interest in the eye area, suggesting that they perceived images
      representing faces. Dogs fixated at the upright faces as long as the inverted
      faces, but the eye area of upright faces gathered longer total duration and
      greater relative fixation duration than the eye area of inverted stimuli,
      regardless of the species (dog or human) shown in the image. Personally, familiar
      faces and eyes attracted more fixations than the strange ones, suggesting that
      dogs are likely to recognize conspecific and human faces in photographs. The
      results imply that face scanning in dogs is guided not only by the physical
      properties of images, but also by semantic factors. In conclusion, in a free
      viewing task, dogs seem to target their fixations at naturally salient and
      familiar items. Facial images were generally more attractive for pet dogs than
      kennel dogs, but living environment did not affect conspecific preference or
      inversion and familiarity responses, suggesting that the basic mechanisms of face
      processing in dogs could be hardwired or might develop under limited exposure.

PMID- 24305997
TI  - Horses (Equus caballus) discriminate body odour cues from conspecifics.
AB  - Knowledge about social recognition and memory in animals can help us to determine
      appropriate management and husbandry techniques. In this study, we used a
      habituation-discrimination procedure to investigate the ability of horses (Equus
      caballus) to distinguish between the body odour samples of unfamiliar
      conspecifics. To pick up body odour, we rubbed material on the coat of horses and
      presented these unknown body odours to 16 different conspecifics of the same sex
      and similar age. The test consisted of two successive two-min presentations of a
      sample from one individual (e.g. individual 'A') and a simultaneous presentation
      of samples from individual 'A' and a novel individual (e.g. individual 'B')
      during a final third presentation. The results showed that horses, regardless of
      sex, decreased the time they spent investigating conspecific body odour across
      the initial two presentations-demonstrating habituation. In the final
      presentation, the results demonstrated successful discrimination of the
      previously experienced odour because horses investigated the novel olfactory
      sample ('B') significantly more than the pre-exposed sample ('A'). Taken
      together, these findings suggest, for the first time, that horses are able to
      discriminate two stimuli derived from body odours of unfamiliar conspecifics over
      short period of time. 

PMID- 24306000
TI  - BCG vaccine for clinically isolated syndrome and MS: infections and protective
      immunity.

PMID- 24305999
TI  - ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis
      imperfecta.
AB  - Integrins are cell-surface adhesion receptors that bind to extracellular matrices
      (ECM) and mediate cell-ECM interactions. Some integrins are known to play
      critical roles in dental enamel formation. We recruited two Hispanic families
      with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole
      exome sequences identified three integrin beta 6 (ITGB6) mutations responsible
      for their enamel malformations. The female proband of Family 1 was a compound
      heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A
      p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T >
      A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6
      transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and
      hemizygous for a transition mutation in Exon 6 of Nance-Horan Syndrome (NHS
      Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease
      causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular
      incisors localized ITGB6 to the distal membrane of differentiating ameloblasts
      and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory
      stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its
      localization was associated with ameloblast modulation. Our findings demonstrate
      that early and late amelogenesis depend upon cell-matrix interactions. Our
      approach (from knockout mouse phenotype to human disease) demonstrates the power
      of mouse reverse genetics in mutational analysis of human genetic disorders and
      attests to the need for a careful dental phenotyping in large-scale knockout
      mouse projects. 

PMID- 24306001
TI  - Neuroimaging and clinical features in type II (late-onset) Alexander disease.
AB  - OBJECTIVE: To describe the imaging and clinical features in type II (late-onset)
      Alexander disease (AxD). METHODS: We retrospectively identified all cases of type
      II AxD evaluated at Mayo Clinic, Rochester from January 1996 to February 2012.
      Clinical and neuroimaging data abstracted from the record included age at onset
      of symptoms, age at diagnosis, first symptom, neurologic symptoms,
      physical/neurologic findings on examination, genetic testing and/or biopsy (if
      performed), and MRI findings. RESULTS: Thirteen patients with type II AxD were
      identified. Median age at onset was 38 years (range: 12-63). Five patients were
      female. Eleven of 13 patients had atrophy of the medulla while all 13 had
      medullary T2 hyperintensity. In 7 patients, these brainstem regions showed patchy
      enhancement. Five subjects had T2 signal change in the middle cerebellar
      peduncle, with associated contrast enhancement in 4 subjects. Eleven of 12
      patients with T2 fluid-attenuated inversion recovery (FLAIR) imaging had pial
      FLAIR signal change in the medulla. Nine of 12 patients with spinal cord imaging
      had cord atrophy, and 3 of 9 of these evaluated with contrast had cervical cord
      enhancement. CONCLUSIONS: Our study confirms prior reports of atrophy and signal
      change of the medulla and spinal cord in late-onset AxD. We expand on previous
      imaging studies by identifying middle cerebellar peduncle and pial FLAIR signal
      changes as important diagnostic clues. Variable patchy enhancement may occur in
      regions of T2 hyperintensity, leading to diagnostic uncertainty. In addition, we
      demonstrate that previously emphasized clinical features such as palatal tremor
      may not be common. We affirm that age at onset predicts clinical phenotype and
      imaging findings.

PMID- 24306002
TI  - Effects of Bacille Calmette-Guerin after the first demyelinating event in the
      CNS.
AB  - OBJECTIVE: To evaluate Bacille Calmette-Guerin (BCG) effects after clinically
      isolated syndromes (CIS). METHODS: In a double-blind, placebo-controlled trial,
      participants were randomly assigned to receive BCG or placebo and monitored
      monthly with brain MRI (6 scans). Both groups then entered a preplanned phase
      with IM interferon-beta-1a for 12 months. From month 18 onward, the patients took
      the disease-modifying therapies (DMTs) that their neurologist considered
      indicated in an open-label extension phase lasting up to 60 months. RESULTS: Of
      82 randomized subjects, 73 completed the study (33 vaccinated and 40 placebo).
      During the initial 6 months, the number of cumulative lesions was significantly
      lower in vaccinated people. The relative risks were 0.541 (95% confidence
      interval [CI] 0.308-0.956; p = 0.03) for gadolinium-enhancing lesions (the
      primary endpoint), 0.364 (95% CI 0.207-0.639; p = 0.001) for new and enlarging T2
      hyperintense lesions, and 0.149 (95% CI 0.046-0.416; p = 0.001) for new T1
      hypointense lesions. The number of total T1-hypointense lesions was lower in the
      BCG group at months 6, 12, and 18: mean changes from baseline were -0.09 +/- 0.72
      vs 0.75 +/- 1.81 (p = 0.01), 0.0 +/- 0.83 vs 0.88 +/- 2.21 (p = 0.08), and -0.21
      +/- 1.03 vs 1.00 +/- 2.49 (p = 0.02). After 60 months, the cumulative probability
      of clinically definite multiple sclerosis was lower in the BCG + DMT arm (hazard
      ratio = 0.52, 95% CI 0.27-0.99; p < 0.05), and more vaccinated people remained
      DMT-free (odds ratio = 0.20, 95% CI 0.04-0.93; p = 0.04). CONCLUSIONS: Early BCG
      may benefit CIS and affect its long-term course. CLASSIFICATION OF EVIDENCE: BCG,
      as compared to placebo, was associated with significantly reduced development of
      gadolinium-enhancing lesions in people with CIS for a 6-month period before
      starting immunomodulating therapy (Class I evidence).

PMID- 24306003
TI  - The underestimation of familial ALS and counseling patients with sporadic ALS.

PMID- 24306004
TI  - Familial clustering of ALS in a population-based resource.
AB  - OBJECTIVE: To determine the extent of an inherited contribution to amyotrophic
      lateral sclerosis (ALS) mortality. METHODS: Death certificates (DCs) from 1904 to
      2009 were analyzed from patients with at least 3 generations recorded in the Utah
      Population Database, a genealogic and medical database of more than 2 million
      Utah residents. Among probands whose DCs listed ALS, the relative risk (RR) of
      death with ALS was determined among spouses and first- through fifth-degree
      relatives, using birth year-, sex-, and birthplace-matched cohorts. RESULTS:
      Eight hundred seventy-three patients with ALS met the inclusion criteria. Among
      3,531 deceased first-degree relatives of probands, the RR of dying with ALS was
      increased compared with control cohorts (RR = 4.91, 95% confidence interval 3.36,
      6.94). The RR of dying with ALS was also increased among 9,386 deceased second
      degree relatives (RR = 2.85, 95% confidence interval 2.06, 3.84). The RR of dying
      with ALS was not increased among third- through fifth-degree relatives. More
      affected first-degree relatives were male (p = 0.014). No cases of conjugal ALS
      were observed. CONCLUSIONS: This study is suggestive of familial clustering in
      excess of expected for ALS. Our results confirm the results of prior studies of
      familial ALS, suggesting applicability of our findings to other mixed European
      populations. Furthermore, this work expands on previous studies by quantifying
      the RR of ALS among more distant relatives. The use of mortality data obtained
      from DCs reduces the ascertainment and recall bias of many previous studies.
      Finally, the excess of ALS among second-degree relatives and lack of conjugal ALS
      are strongly supportive of a genetic contribution.

PMID- 24306005
TI  - The questionable use of unequal allocation in confirmatory trials.
AB  - Randomization is the standard means for addressing known and unknown confounders
      within the patient population in clinical trials. Although random assignment to
      treatment arms on a 1:1 basis has long been the norm, many 2-armed confirmatory
      trials now use unequal allocation schemes where the number of patients receiving
      investigational interventions exceeds those in the comparator arm. In what
      follows, we offer 3 arguments for why investigators, institutional review boards,
      and data and safety monitoring boards should exercise caution when planning or
      reviewing 2-armed confirmatory trials involving unequal allocation ratios. We
      close by laying out some of the conditions where uneven allocation can be
      justified ethically.

PMID- 24306006
TI  - Enzyme-free fluorescent-amplified aptasensors based on target-responsive DNA
      strand displacement via toehold-mediated click chemical ligation.
AB  - A new target-responsive DNA strand displacement system via toehold-mediated click
      chemical ligation was designed and prepared for enzyme-free fluorescent-amplified
      aptasensors. The aptasensors significantly amplified fluorescent signals in
      response to targets based on target recycling processes. 

PMID- 24306007
TI  - Expanded sexually transmitted infection surveillance efforts in the United States
      military: a time for action.

PMID- 24306008
TI  - The unrecognized role of the FDA microanalytical analyst.

PMID- 24306009
TI  - Evaluating the nutrition intake of U.S. military service members in garrison.
AB  - Sparse information exists on the nutrition intake of U.S. military service
      members in a garrison setting. The purpose of this study was to assess the eating
      habits of a small group of service members who had not deployed in the preceding
      12 months. Nutrition intake was measured using an online food frequency
      questionnaire and anthropometric measurements taken. Correlations were used to
      assess relationships between total caloric intake and sex, age, weight, waist
      circumference, body mass index, rank, marital status, history in a service
      specific weight control program, and time in service. There were 39 subjects (18
      males, 21 females) enrolled. There was a significant difference in total caloric
      intake between males and females (p = 0.040). The relationships of total caloric
      intake to both weight and waist circumference were significant (r = 0.425, p =
      0.007 and r = 0.393, p = 0.013). There was a modest relationship between total
      caloric intake and sex (r = 0.331, p = 0.040) and history in a weight control
      program (r = -0.313, p = 0.052). There was no significant correlation between
      body mass index, age, rank, marital status, time in service, and total caloric
      intake. These relationships may partially explain the eating habits of service
      members in garrison. Future studies should further assess intake and influential
      additional factors, such as deployments. 

PMID- 24306010
TI  - High-resolution ultrasound findings in the symptomatic residual limbs of
      amputees.
AB  - INTRODUCTION: Amputations are increasingly prevalent because of medical
      complications associated with diabetes, meningitis, peripheral vascular disease,
      and neoplasms as well as road traffic accidents and war. The use of ultrasound
      (U/S) to diagnose the cause of pain in the residual limb of amputees is presented
      together with a review of the literature. PATIENTS AND METHODS: 133 civilian
      patients with one or more amputations were included in the study. They were seen
      over a 2-year period, at the Douglas Bader Unit, Queen Mary's Hospital,
      Roehampton, Surrey, United Kingdom, in an outpatient setting. Patients were
      scanned using a Philips ATL/HDI 5000 U/S scanner. RESULTS: There were 89 male and
      44 female patients, age range 14 to 91 years, with a total of 136 amputated
      sites. 80% of amputations involved the lower limb. Neuromas were the most
      frequently found lesions, followed by inflammatory edema, soft-tissue
      calcifications, bony spurs, soft-tissue infection, overuse injuries, bursae, and
      skin lesions. Scar tissue, bony erosion, bone infection, aneurysm formation,
      venous thrombosis, and myodesis failure were less frequently seen. CONCLUSIONS:
      There is a wide spectrum of lesions in the amputated limb, which can be
      visualized by high-resolution U/S. Neuromas were the most frequent lesions seen.

PMID- 24306011
TI  - Randomized controlled trial of accelerated resolution therapy (ART) for symptoms
      of combat-related post-traumatic stress disorder (PTSD).
AB  - OBJECTIVES: Therapies for post-traumatic stress disorder (PTSD) endorsed by the
      Department of Defense and Veterans Administration are relatively lengthy, costly,
      and yield variable success. We evaluated Accelerated Resolution Therapy (ART) for
      the treatment of combat-related psychological trauma. METHODS: A randomized
      controlled trial of ART versus an Attention Control (AC) regimen was conducted
      among 57 U.S. service members/veterans. After random assignment, those assigned
      to AC were offered crossover to ART, with 3-month follow-up on all participants.
      Self-report symptoms of PTSD and comorbidities were analyzed among study
      completers and by the intention-to-treat principle. RESULTS: Mean age was 41 +/-
      13 years with 19% female, 54% Army, and 68% with prior PTSD treatment. The ART
      was delivered in 3.7 +/- 1.1 sessions with a 94% completion rate. Mean reductions
      in symptoms of PTSD, depression, anxiety, and trauma-related guilt were
      significantly greater (p < 0.001) with ART compared to AC. Favorable results for
      those treated with ART persisted at 3 months, including reduction in aggression
      (p < 0.0001). Adverse treatment-related events were rare and not serious.
      CONCLUSIONS: ART appears to be a safe and effective treatment for symptoms of
      combat-related PTSD, including refractory PTSD, and is delivered in significantly
      less time than therapies endorsed by the Department of Defense and Veterans
      Administration.

PMID- 24306012
TI  - Secondary traumatic stress in military primary and mental health care providers.
AB  - The purpose of this study was to explore rates of secondary traumatic stress
      (STS) in a sample of 70 military primary and mental health care providers. The
      sample included working professionals within two military hospitals. Participants
      completed surveys containing a demographic questionnaire and the Secondary
      Traumatic Stress Scale. Results of data analysis found military participants in
      the sample to be experiencing relatively low rates of STS. Over half of the
      sample reported endorsing at least one symptom of STS occurring within the last
      week, whereas 8% of participants indicated moderate to high symptomatology. The
      most frequently reported symptoms were feeling emotionally numb and trouble
      sleeping followed by the intrusive thoughts about clients. The least frequently
      reported symptom was feeling jumpy. Implications of study findings and
      recommendations for future research are outlined. 

PMID- 24306013
TI  - Postdeployment experiences of military mental health providers.
AB  - The deployment experiences of military mental health providers (MMHP) since
      September 2001 have been largely unexamined. MMHP are an integral part to the
      military health system and play a key role in maintaining a fit fighting force.
      MMHP deploy and are expected to help others manage their deployment experiences
      while being faced with their own emotional challenges during deployment and while
      transitioning home. This study examines two questions: First, how do MMHP
      experience reintegration to their families and jobs after being deployed, and
      second, how do MMHP assess and cope with their own postdeployment issues. In this
      study, 27 mental health professionals including social workers, psychiatrist, and
      psychologist were interviewed to examine their deployment and postdeployment
      experiences. Results indicated 81% of MMHP recognized some level of dysfunction
      in their lives, at home, at work, or at both, upon their return from deployment.
      The ability for MMHP to manage their own reintegration issues has significance
      for their own personal well-being as well as their ability to provide specialized
      care for others. Attention needs to be given to how MMHP are supported
      postdeployment and possibly tailor a transitional process for postdeployment
      reintegration based on the unique nature of their work. 

PMID- 24306014
TI  - Evaluating the benefits of a live, simulation-based telebehavioral health
      training for a deploying army reserve unit.
AB  - Telebehavioral health (TBH) has previously been reported as underutilized in the
      Afghan Theater of Operations despite efforts to expand the number of operational
      TBH sites. A lack of training on TBH services and equipment was identified as a
      probable cause. The National Center for Telehealth and Technology (T2) provided
      members of the 1972nd Medical Detachment (Combat Stress Control [CSC]) U.S. Army
      Reserve with an in-person TBH training designed to provide the unit with hands-on
      knowledge and skills to deliver TBH services in theater. A key training component
      consisted of placing unit members in live, simulated clinical and technical
      scenarios they were likely to encounter while deployed. Evaluations suggest that
      the training was successful at preparing the 1972nd CSC for its TBH mission.
      During its deployment, the 1972nd CSC led an approximate 40% expansion of TBH
      services, including the direct provision of around 700 clinical encounters.
      Several best practice recommendations were identified including: (1) maintain the
      hands-on component, (2) use lessons learned to develop scenarios, (3) incorporate
      training into daily activities, and (4) tailor training while ensuring that all
      stakeholders have the same base knowledge set. To our knowledge, this is the most
      comprehensive process improvement evaluation of a predeployment telehealth
      training available. 

PMID- 24306015
TI  - Effect of center-based counseling for veterans and veterans' families on long
      term mental health outcomes.
AB  - The Veterans and Veterans Families Counselling Service (VVCS), established by the
      Australian government, plays a pivotal role in providing mental health services
      to veterans and their families. This research explored the impact of center-based
      psychological counseling on depression, anxiety, stress, and alcohol use
      severity. A stratified sample of VVCS clients were invited to participate in this
      study. Data were collected on intake to the program, at the fifth counseling
      session, and 12 months after the commencement of counseling. Repeated-measures
      general linear model analyses were conducted to examine the impact of center
      based counseling on depression, anxiety, stress, and alcohol severity over time.
      VVCS center-based counseling resulted in a significant reduction in depression,
      anxiety, stress, and alcohol use severity after five sessions, and these
      improvements were maintained over the next 12 months. Despite these improvements,
      however, participants continued to report moderate-to-severe levels of mental
      health problems. VVCS center-based counseling successfully reduced depression,
      anxiety, stress, and alcohol use symptom severity of veterans and their families.
      However, the clinical profiles of this population are often complex and
      challenges remain in terms of addressing the mental health needs of this group. 

PMID- 24306016
TI  - Comfort levels of active duty gay/bisexual male service members in the military
      healthcare system.
AB  - Before a revision of the "Don't Ask, Don't Tell" policy in 2010, sexual behaviors
      that lesbian, gay, and bisexual service members disclosed to military healthcare
      providers (MHCPs) were grounds for discharge. However, after the revision,
      service members either did not know about the revision, or were still
      uncomfortable approaching MHCPs. This study examined the comfort levels of active
      duty gay/bisexual males approaching MHCPs about sexuality/sexual health concerns.
      Using a quantitative descriptive approach, the 31-item survey developed for this
      study provided initial research data to inform future studies on this topic. The
      survey was available to participants from March 2 to April 3, 2012. Analyzing
      responses from 30 participants, the data revealed a strong correlation between
      service members' comfort disclosing their sexual orientation to a MHCP and their
      perception of how the military cares about them as a sexual minority. The data
      suggested differences in comfort levels among age cohorts disclosing their sexual
      orientation, in addition to differences between officers and enlisted men
      concerning the cost of seeing a nonmilitary healthcare provider. MHCPs should
      understand that establishing a relationship with service members that encourages
      disclosure can improve their view of the military healthcare system and help
      address sexual health concerns. 

PMID- 24306017
TI  - Impact of illness per ICD-9 classification on progression to physical evaluation
      board for U.S. marines placed on limited duty status 2006-2010.
AB  - Mission readiness is of paramount importance to Marine Corps commanders.
      Personnel medically unable to perform at full capacity negatively affect a unit's
      readiness and ability to accomplish mission objectives. A retrospective cohort
      study was designed to evaluate the impact of diseases and conditions per
      International Statistical Classification of Diseases and Related Health Problems,
      Revision 9 (ICD-9) classification of primary diagnosis on likelihood of
      progressing to Physical Evaluation Board (PEB) for U.S. Marines placed on Limited
      Duty. A total of 30,937 records belonging to 19,042 unique individuals were
      identified in the Medical Board Online Tri-Service Tracking System database over
      the study surveillance period. Approximately half (9,133) of all Marines placed
      on Limited Duty were eventually referred to PEB. After multivariate adjustment
      Marines with a primary ICD-9 diagnosis indicating a blood disorder (OR = 4.1, 95%
      CI 2.1-8.1) or nervous system disorder (OR = 3.3, 95% CI 2.8- 3.8) were at
      greater risk of progressing to PEB as compared to the lowest risk group, Marines
      with an orthopedic diagnosis. Occupational category, rank grouping,
      race/ethnicity, and ICD-9 category had statistically significant impacts of
      varying magnitude on the risk of progressing to PEB; no significant difference
      was found for sex. 

PMID- 24306018
TI  - Perspectives from Ethiopia regarding U.S. military humanitarian assistance: how
      to build a better medical civil action project (MEDCAP).
AB  - Assuming that budgetary constraints continue over the next several years, the
      U.S. military's overseas medical activities including medical civic action
      projects (MEDCAPs) and humanitarian assistance projects could comprise an
      increasing proportion of the contributions of U.S. government (USG) to improving
      global health. We have identified several issues with MEDCAPs in Ethiopia since
      2009 that resulted in delays or project cancellations. These were mostly related
      to lack of a plan to develop sustainable capacities. Although there are many
      obvious medical needs for civilian populations in Ethiopia, the provision of
      sustainable development assistance involving these Ethiopian populations on
      behalf of the USG is a complex undertaking involving coordination with many
      partners and coordination with several other USG agencies. Military medical
      professionals planning MEDCAPs and other cooperative global health projects would
      benefit from consultation and close coordination with U.S. Centers for Disease
      Control and Prevention (CDC) and U.S. Agency of International Development (USAID)
      experts who are involved in supporting medium- and long-term health projects in
      Ethiopia. The establishment of durable military medical academic relationships
      and involvement of overseas military medical research units could also help
      promote sustainable projects and build robust professional relationships in
      global health. 

PMID- 24306019
TI  - Cost effectiveness of two army physical fitness programs.
AB  - Repeated failure in the Army Physical Fitness Test (APFT) is associated with
      lower fitness level, premature discharge, and significant career disruption, at
      high economic and health costs to the individual soldier and the U.S. Army. We
      used cost-effectiveness analysis to estimate the health and economic implications
      of two exercise interventions for Army National Guard (ARNG) soldiers who had
      failed the APFT, a traditional remediation program and a new pedometer-based
      program called Fitness for Life, involving individual counseling and follow-up
      telephone calls. Effectiveness of the interventions was analyzed in terms of APFT
      pass rates and calculated 10-year coronary heart disease risk. Costs were
      calculated based on tracking of resources used in the programs. APFT pass rates
      were 54.3% and 47.9%, respectively, for traditional and Fitness for Life
      programs, p = not significant. Neither program affected 10-year coronary heart
      disease risk. For assumed APFT pass rates up to 40% without any formal
      remediation, both the traditional remediation program and the ARNG Fitness for
      Life intervention had cost savings without significant group differences.
      Depending on the ARNG unit and personnel preference, although the Fitness for
      Life Program was more expensive and thus less cost-effective, either program
      could be cost-effective and of benefit to the military. 

PMID- 24306020
TI  - Association among functional-movement ability, fatigue, sedentary time, and
      fitness in 40 years and older active duty military personnel.
AB  - Identifying potential modifiable determinants of functional movement ability and
      fatigue may inform efforts to maintain constant physical readiness, especially in
      active duty military over 40 years of age, who are largely sedentary throughout
      their work day. The primary aim of this study was to determine the associations
      among conventional fitness measures (body composition, flexibility, and
      strength), sedentary behavior (sitting time), functional movement ability, and
      fatigue in military personnel. Volunteer active duty personnel 40 years of age
      and older (n = 569 males; n = 121 females; mean +/- SD for total sample = 44.5 +/
      4.1 years) were assessed for adiposity (%Fat), strength, flexibility, self
      reported sitting time, perceived fatigue using the fatigue severity scale, and
      functional movement ability using the functional movement screening criteria.
      Greater flexibility was associated with better functional movement screening
      scores (r = 0.34, p < 0.05), and waist circumference and %Fat were inversely
      related to function (r = -0.26 and -0.21, p < 0.05). Furthermore, less sitting
      time (p < 0.001) was associated with less fatigue. Our data suggest that exercise
      training, reductions in daily sitting time, and weight management may be viable
      intervention targets to enhance functional movement ability and reduce fatigue in
      40+ year old active duty military personnel. 

PMID- 24306021
TI  - Clinical prediction of musculoskeletal-related "medically not ready" for combat
      duty statuses among active duty U.S. army soldiers.
AB  - No evidence-based mechanism currently exists to inform U.S. Army clinicians of
      soldiers at risk of being found "Medically Not Ready" for combat duty.
      Historically, musculoskeletal conditions represent high-frequency medical
      problems among Army soldiers. We explored the feasibility of using centrally
      archived medical and administrative data on Army soldiers in the automated
      prediction of musculoskeletal-related Medically Not Ready soldiers who did not
      deploy. We examined 56,443 active duty U.S. Army soldiers who underwent precombat
      medical screening during March through December 2009 and in March 2010.
      Musculoskeletal problems were associated with 23.0% of nonreadiness cases in the
      study population. We used multivariable logistic regression in derivation cohorts
      to compute risk coefficients and cut points. We then applied these coefficients
      to covariates in validation cohorts, simulating predictions 2 to 3 months before
      their medical screenings. The analysis yielded c statistics ranging from 83 to
      90%. The predictions identified 45 to 73% and 50 to 82% of the individual male
      and female outcome-positive soldiers, respectively, while obtaining 83 to 95%
      specificity. Our findings demonstrate the potential of Army data to create
      evidence-based estimates of nonreadiness risk. These methods could enable earlier
      patient referrals and improved management, and potentially reduce medically
      related nondeployment. 

PMID- 24306022
TI  - Medical museum, 2nd surgical hospital.
AB  - When his unit, the 2nd Surgical Hospital (MA), was established at An Khe in
      January 1966, MAJ Rich began collecting retrieved foreign bodies along with
      documentation of the wound. A museum displaying these objects was established at
      one end of the operating room Quonset hut. During Rich's tour of duty, there were
      324 cases where the patient was wounded by a punji stick, representing 38% wounds
      because of hostile action. 

PMID- 24306023
TI  - Transmission of vaccinia virus, possibly through sexual contact, to a woman at
      high risk for adverse complications.
AB  - Severe adverse events, including eczema vaccinatum (EV), can result after
      smallpox vaccination. Persons at risk for EV include those with underlying
      dermatologic conditions, such as atopic dermatitis. We investigated a case of
      vaccinia infection, possibly acquired during sexual contact with a recently
      vaccinated military service member, in a female Maryland resident with atopic
      dermatitis. The U.S. Department of Defense's Vaccine Healthcare Centers Network
      (VHCN) and the Centers for Disease Control and Prevention (CDC) worked in
      conjunction with the patient's physician and the Maryland Department of Health
      and Mental Hygiene (DHMH) to confirm the diagnosis, ensure treatment, and prevent
      further transmission. Specimens collected from the patient were tested at the
      DHMH laboratories and were positive by real-time polymerase chain reaction for
      nonvariola orthopoxvirus. Testing at the CDC verified the presence of vaccinia
      specific DNA signatures. Continuing spread of the patient's lesions led to the
      administration of vaccinia immune globulin and strict infection control measures
      to prevent tertiary transmission to vulnerable family members, also with atopic
      dermatitis. VHCN contacted the service member to reinforce vaccination site care
      and hygiene. This case underscores the importance of prevaccination education for
      those receiving the smallpox vaccine to protect contacts at risk for developing
      severe adverse reactions. 

PMID- 24306024
TI  - Sprengel deformity presenting as a post-traumatic injury in an afghan boy: a case
      report.
AB  - Sprengel deformity is a rare congenital anomaly that involves the shoulder joint
      and scapula. We treated a young Afghan boy who was presented to the German Level
      II Provincial Reconstructive Team in Kunduz, Afghanistan, with the complaint of a
      shoulder deformity evolving after an accident that occurred several years before
      the presentation of the patient to clinic. Physicians maximized the available
      resources for the diagnostic workup by arranging for his computed tomography scan
      at the German Level III Hospital at Mazar-e-Sharif and then reviewing the study
      through teleradiology. The presence of a Coalition Surgical Team allowed the
      delivery of advanced surgical care by combining the specialized surgical skills
      of three upper extremity surgeons deployed to the area. 

PMID- 24306025
TI  - Salmonella septic arthritis in a patient receiving etanercept: case report and
      review of the literature.
AB  - Antitumor necrosis factor alpha agents are known to increase the risk for severe
      and atypical infections. Numerous atypical organisms have been reported
      previously, however, there is a paucity of reports of Salmonella as a
      complication of these therapies. We report a case of a 69-year-old female who
      developed Salmonella septic arthritis of the pubic symphysis while taking
      etanercept that resolved with cessation of etanercept and antibiotic treatment
      and we review the literature regarding this complication. Awareness of
      susceptibility to Gram-negative intracellular organisms and reactivation of
      dormant infections due to the mechanism of action of antitumor necrosis factor
      alpha medications is vital. 

PMID- 24306026
TI  - Ehd3, a regulator of vesicular trafficking, is silenced in gliomas and functions
      as a tumor suppressor by controlling cell cycle arrest and apoptosis.
AB  - EHD3 [Eps15 homology (EH) domain-containing protein 3] is a protein that resides
      in tubular and vesicular membrane structures and participates in endocytic
      recycling, although all its functions are unknown. Since Ehd3 is most abundantly
      expressed in brain tissues, we examined its role in brain cancer progression.
      Using immunohistochemistry, we report loss of EHD3 expression in gliomas,
      including low-grade astrocytomas, suggesting that this is an early event in
      gliomagenesis. EHD3 expression is also very low in most of glioma cell lines
      tested. In two cell lines, a bisulfite sequencing method identifies promoter
      hypermethylation as a mechanism of Ehd3 silencing, and its expression was
      restored by the demethylating agent 5-Azacytidine. Doxycycline-inducible
      restoration of EHD3 expression to glioma cells decreases their growth and
      invasiveness and induces cell cycle arrest and apoptosis. Furthermore, shRNA
      mediated Ehd3 silencing increases cell growth. Using a xenograft model, we
      demonstrate Ehd3 growth inhibitory functions in glioma cells in vivo. We suggest
      that Ehd3 functions as a tumor suppressor gene and loss of its expression is a
      very common event in gliomas. This is the first study to highlight the importance
      of a member of the C-terminal EHD proteins in cancer and to link their functions
      to the cell cycle and apoptosis. 

PMID- 24306027
TI  - Identification of novel sequence variations in microRNAs in chronic lymphocytic
      leukemia.
AB  - MicroRNA (miRNA) expression is deregulated in many tumors including chronic
      lymphocytic leukemia (CLL). Although the particular mechanism(s) responsible for
      their aberrant expression is not well characterized, the presence of mutations
      and single-nucleotide polymorphisms (SNPs) in miRNA genes, possibly affecting
      their secondary structure and expression, has been described. In CLL; however,
      the impact and frequency of such variations have yet to be elucidated. Using a
      custom resequencing microarray, we screened sequence variations in 109 cancer
      related pre-miRNAs in 98 CLL patients. Additionally, the primary regions of miR
      29b-2/29c and miR-16-1 were analyzed by Sanger sequencing in another cohort of
      213 and 193 CLL patients, respectively. Altogether, we describe six novel miR
      sequence variations and the presence of SNPs (n = 27), most of which changed the
      miR-secondary structure. Moreover, some of the identified SNPs have a
      significantly different frequency in CLL when compared with a control population.
      Additionally, we identified a novel variation in miR-16-1 that had not been
      described previously in CLL patients. We show that this variation affects the
      expression of mature miR-16-1. We also show that the expression of another miRNA
      with pathogenetic relevance for CLL, namely miR-29b-2, is influenced by the
      presence of a polymorphic insertion, which is more frequent in CLL than in a
      control population. Altogether, these data suggest that sequence variations may
      occur during CLL development and/or progression. 

PMID- 24306028
TI  - The continuing evolution of theAmerican Journal of Tropical Medicine & Hygiene.

PMID- 24306029
TI  - Non-trophic cutaneous ulcers in lepromatous leprosy.

PMID- 24306030
TI  - Gains and future road map for the elimination of dog-transmitted rabies in the
      Americas.

PMID- 24306031
TI  - 17D Yellow Fever Virus Vaccine.

PMID- 24306032
TI  - In response.

PMID- 24306033
TI  - Environmental factors influencing epidemic cholera.

PMID- 24306034
TI  - In response.

PMID- 24306035
TI  - Viral load for HIV treatment failure management: a report of eight drug-resistant
      tuberculosis cases co-infected with HIV requiring second-line antiretroviral
      treatment in Mumbai, India.

PMID- 24306039
TI  - Cross-national prevalence and cultural correlates of bipolar I disorder.
AB  - PURPOSE: Bipolar disorder has been consistently related to heightened sensitivity
      to reward. Greater reward sensitivity predicts the onset of disorder, a more
      severe course, and conversion from milder to severe forms. No studies consider
      whether cultural factors related to reward sensitivity influence the course of
      bipolar disorder. This study examines the relationship of reward-relevant
      cultural values to global prevalence rates of bipolar I disorder. METHODS:
      Lifetime prevalence of bipolar I disorder for 17 countries was drawn from
      epidemiological studies that used structured diagnostic interviews of large
      community samples. Bivariate correlations were used to assess the relationship of
      bipolar disorder prevalence with national scores on four reward-relevant cultural
      dimensions (Power Distance, Individualism, Long-Term Orientation, and Performance
      Orientation). RESULTS: The prevalence of bipolar I disorder was correlated in the
      predicted manner with Power Distance and Individualism, and with Long-Term
      Orientation and Performance Orientation after outliers were removed. CONCLUSIONS:
      Findings provide evidence for a cultural model of reward sensitivity in bipolar
      disorder.

PMID- 24306040
TI  - Integrated models in psychiatry: the state of the art.

PMID- 24306041
TI  - Suicide attempt in young people: a signal for long-term health care and social
      needs.
AB  - IMPORTANCE: Suicidal behavior has increased since the onset of the global
      recession, a trend that may have long-term health and social implications.
      OBJECTIVE: To test whether suicide attempts among young people signal increased
      risk for later poor health and social functioning above and beyond a preexisting
      psychiatric disorder. DESIGN: We followed up a cohort of young people and
      assessed multiple aspects of their health and social functioning as they
      approached midlife. Outcomes among individuals who had self-reported a suicide
      attempt up through age 24 years (young suicide attempters) were compared with
      those who reported no attempt through age 24 years (nonattempters). Psychiatric
      history and social class were controlled for. SETTING AND PARTICIPANTS: The
      population-representative Dunedin Multidisciplinary Health and Development Study,
      which involved 1037 birth cohort members comprising 91 young suicide attempters
      and 946 nonattempters, 95% of whom were followed up to age 38 years. MAIN
      OUTCOMES AND MEASURES: Outcomes were selected to represent significant individual
      and societal costs: mental health, physical health, harm toward others, and need
      for support. RESULTS: As adults approaching midlife, young suicide attempters
      were significantly more likely to have persistent mental health problems (eg,
      depression, substance dependence, and additional suicide attempts) compared with
      nonattempters. They were also more likely to have physical health problems (eg,
      metabolic syndrome and elevated inflammation). They engaged in more violence (eg,
      violent crime and intimate partner abuse) and needed more social support (eg,
      long-term welfare receipt and unemployment). Furthermore, they reported being
      lonelier and less satisfied with their lives. These associations remained after
      adjustment for youth psychiatric diagnoses and social class. CONCLUSIONS AND
      RELEVANCE: Many young suicide attempters remain vulnerable to costly health and
      social problems into midlife. As rates of suicidal behavior rise with the
      continuing global recession, additional suicide prevention efforts and long-term
      monitoring and after-care services are needed.

PMID- 24306042
TI  - Hepcidin and ferritin blood level as noninvasive tools for predicting breast
      cancer.
AB  - BACKGROUND: Currently used CA15-3 and CEA have found their clinical application
      particularly in the follow-up of patients with advanced disease. Novel biomarkers
      are urgent, especially for improving early diagnosis as well as for
      discriminating between benign and malignant disease. PATIENTS AND METHODS: In the
      present study, we used a proteomic approach based on surface-enhanced laser
      desorption/ionization-time of flight-mass spectrometry screening with the aim of
      identifying differentially expressed 2-30 kDa proteins in plasma of patients with
      malignant (65 cases) and benign (88 cases) breast lesions with respect to 121
      healthy controls. RESULTS: We found that the most promising SELDI peaks were
      those corresponding to hepcidin-25 and ferritin light chain. We evaluated the
      capability of these peaks in predicting malignant and benign breast lesions using
      the area under the receiver operating characteristic curve (AUC). The results
      showed a good capacity to predict malignant breast lesions for hepcidin-25 [AUC:
      0.82; 95% confidence interval (CI) 0.75-0.90] and ferritin light chain (AUC:
      0.86; 95% CI 0.79-0.92). Conversely, a weak and satisfactory capability to
      predict benign breast lesion was observed for hepcidin-25 (AUC: 0.63; 95% CI 0.41
      0.85) and ferritin light chain (AUC: 0.73; 95% CI 0.49-0.97). A significant
      association between HER2 status and hepcidin-25 was observed and the distribution
      of transferrin and ferritin were found significantly different in patients with
      breast cancer when compared with that of controls. CONCLUSIONS: This study
      provides evidence that hepcidin and ferritin light chain level in plasma may be
      of clinical usefulness to predict malignant and benign disease with respect to
      healthy controls.

PMID- 24306043
TI  - Arterial supply of the distal humerus.
AB  - PURPOSE: Distal humeral fractures are rare, but severe injuries, the treatment of
      which is often accompanied by serious complications and its outcome strongly
      depends on the quality of surgical therapy. Non-union is a common entity,
      compromising clinical results and requiring revision surgery. Osteonecrosis is an
      underestimated etiologic factor in the development of non-union. The present
      study aims to display the distribution patterns of the arterial vessels at the
      distal humerus, to correlate the displayed vessels with local nutrient foramina
      and to disclose an endangerment of these structures by common osteosynthetic
      implants. METHODS: Eight plastinated fresh frozen upper extremities were
      digitally analyzed regarding the vascular density of the cancellous bone, by
      calculating the ratio of area comprised by arterial vessels and the area
      comprised by cancellous bone on sagittal cuts of the distal humerus. Possible
      differences in the vascular density of the medial epicondylar region, the lateral
      epicondylar region and a watershed area between the epicondyles and distal to the
      supracondylar region were investigated. On the basis of 200 macerated humeri, the
      distribution pattern of cortical nutrient foramina and their anatomic relation to
      properly applied common distal humerus plates were documented. RESULTS: The data
      show a significantly higher density of vessels per cancellous bone in the
      epicondylar regions than in the watershed region (p < 0.000, median 0.148 vs.
      0.103). The analysis of the nutrient foramina showed distinct distribution
      patterns with a single foramen over the medial epicondyle (55 specimens, 27.5 %)
      and an area of several foramina at the posterior part of the lateral epicondyle
      (200 of the specimens, 100 %). In almost every specimen, the application of the
      osteosynthetic implants led to an overlay over the investigated nutrient
      foramina. DISCUSSION: Osteonecrosis and non-union are severe complications in the
      surgical treatment of distal humeral fractures. The biology of the bone,
      especially the blood supply, has to be respected as much as possible during open
      procedures, to optimize bony healing. This has to be considered when performing
      periosteal stripping or applying osteosynthetic plates over the postero-lateral
      and medial epicondyle. The watershed area of the distal humerus has to be
      considered as being prone to minor arterial blood supply and thereby non-union is
      possible, if the arterial vessels coming from the epicondyles are destroyed.

PMID- 24306044
TI  - The use of ultrasound improves the accuracy of epidural needle placement in
      cadavers.
AB  - PURPOSE: To investigate whether epidural-prepuncture ultrasound imaging improves
      the accuracy and quality of epidural needle placement or not? METHODS: By
      recruiting 15 cadavers, a total of 90 epidural needle punctures to access
      epidural space in study group with the help of ultrasound imaging at lumbar and
      thoracic spinal segments were attempted. A similar number of punctures in a
      control group were also performed without ultrasound imaging involving the
      intervertebral spaces adjacent to the ones used for ultrasound guided punctures.
      The accuracy of needle tip placement was ascertained with the help of computed
      axial tomography. Six variables: puncture depth and needle angle, procedure time,
      number of attempts per space, steps in needle advances, number of bony contacts
      and number of spaces attempted, were studied and compared among the groups.
      RESULTS: The accuracy of epidural needle placement and quality of the procedure
      in study group were superior to the control group. CONCLUSIONS: The pre-procedure
      ultrasound imaging enhances the accuracy and quality of epidural needle
      placement.

PMID- 24306045
TI  - [Peripherial talar fractures].
AB  - OBJECTIVE: Open reduction and internal fixation with screw(s) for fragments with
      sufficient size, and resection of smaller fragments. INDICATIONS: Displaced
      fragments with (typical) involvement of joint surface. CONTRAINDICATIONS: Active
      infection and severe peripherial vascular disease. SURGICAL TECHNIQUE:
      Positioning and approach are adapted to the fracture location. Fractures of the
      talar head and talar shoulders, supine position and anteromedial/-lateral
      approach. Fractures of the lateral talar process, lateral position on
      contralateral side and lateral approach. Fractures of the posterior talar
      process, prone position and posterolateral approach. Fractures of the medial,
      supine position and medial approach. Open reduction and internal screw fixation.
      Cartilage-surgical procedures for concomitant chondral defects. POSTOPERATIVE
      MANAGEMENT: For the first 6 weeks, 15 kg partial weight bearing without orthosis
      in a standard shoe. Thrombosis prophylaxis following the local standard during
      the time of partial weight bearing. RESULTS: At a specialized orthopedic hospital
      with a supraregional frequented department for foot and ankle surgery, 8 patients
      with peripherial talar fractures were treated in 2012 (medial/posterior talar
      process, each n = 1, lateral talar process, n = 2, medial and lateral talar
      shoulder, each n = 2). One fragment was fixed with 1-3 screws, and additional
      cartilage reconstruction with matrix-associated stem cell transplantation was
      performed in 4 cases (lateral talar process, n = 2, medial and lateral talar
      shoulder, each n = 1). Bony fusion was registered at the 6-week follow-up in all
      cases. Further follow-up is not completed. Complications have not been registered
      so far.

PMID- 24306046
TI  - [Operative treatment of central talar fractures].
AB  - OBJECTIVE: Anatomic reduction of talar neck and body fractures with axial
      realignment and restoration of the articular surfaces of the talus. INDICATIONS:
      Displaced talar neck and body fractures. CONTRAINDICATIONS: High perioperative
      risk, soft tissue infection, neurogenic osteoarthropathy. SURGICAL TECHNIQUE:
      Reduction of the axial alignment of the talus and its joints via bilateral
      approaches according to the preoperative CT-based planning. A medial malleolar
      osteotomy may be necessary to approach the talar dome. The blood supply via the
      deltoid ligament and the sinus tarsi has to be respected. Manipulation of the
      main fragments with K-wires introduced temporarily; a mini-distractor is helpful
      in restoring the length. Internal fixation is tailored to the individual fracture
      pattern, including conventional and headless screws, bioresorbable pins, lost K
      wires, and/or minifragment plates. Joint transfixation for 6 weeks to ensure
      ligamentous healing if instability persists after internal fixation. With severe
      soft tissue damage, temporary tibiometatarsal external fixation is applied until
      soft tissue consolidation. POSTOPERATIVE MANAGEMENT: Range of motion exercises of
      the ankle and subtalar joints starting postoperative day 2 except for cases with
      joint transfixation. Partial weight bearing of 20 kg for 10-12 weeks. Use of a
      cast or walker for 6 weeks followed by intensive active and passive range of
      motion exercises of the ankle and subtalar joints. RESULTS: Over 8 years 79
      fractures of the talar neck and body were treated. In all, 43 patients with 45
      talar neck (n = 30) and body (n = 15) fractures were re-examined clinically and
      radiologically (mean follow-up 3 years). Definite treatment consisted of open
      reduction and screw fixation of the talus in 41 cases and small plate fixation in
      2 cases supplemented by temporary external fixation for 1-3 weeks in 12 cases. At
      follow-up, the Maryland Foot Score averaged 86.1 and the AOFAS Ankle/Hindfoot
      Score averaged 78.9. The Hawkins classification was of prognostic value in talar
      neck fractures. The functional results and the rate of avascular necrosis (AVN)
      were unaffected by the time to definite internal fixation. AVN was observed in 11
      cases (24%); with only partial AVN involving less than one third of the talar
      body in 8 of these patients. Due to complete AVN with collapse of the talar dome,
      3 patients (6.7%) required fusion. Signs of posttraumatic arthritis of the
      tibiotalar or subtalar joint were seen in 21 cases (47%). The rate of symptomatic
      posttraumatic arthritis correlated with the occurrence of total AVN, but not with
      partial AVN.

PMID- 24306047
TI  - Fractures of the sustentaculum tali.
AB  - OBJECTIVE: Anatomical reconstruction of displaced sustentaculum tali fractures
      via a direct medial approach. INDICATIONS: Displaced fractures of the
      sustentaculum tali with incongruity or depression of the medial facet of the
      subtalar joint, entrapment of the flexor hallucis longus or flexor digitorum
      longus tendons, fracture line extending into the posterior facet of the subtalar
      joint. CONTRAINDICATIONS: Infected or grossly contaminated soft tissue, severely
      restricted vascular supply to the foot, high perioperative risk. SURGICAL
      TECHNIQUE: Direct medial approach over the sustentaculum tali, retraction of the
      tendons, joint exploration, fracture reduction using the medial facet and
      cortical outline as guidelines, fracture fixation with two small fragment screws
      from medial to lateral directed slightly plantarly and posteriorly. Fractures
      with depression of the medial facet as a whole can alternatively be reduced and
      fixed percutaneously. POSTOPERATIVE MANAGEMENT: Lower leg splint for 5-7 days,
      partial weight-bearing with 20 kg for 6-8 weeks (until radiographic signs of
      consolidation) in the patient's own shoewear, early range of motion exercises of
      the ankle, subtalar and mid-tarsal joints. RESULTS: Over a course of 15 years, 31
      patients were treated operatively for sustentacular fractures. In all, 27
      patients (87%) had additional fractures to the same foot and ankle. Eighteen
      patients with a mean age of 41 years treated at our institution with screw
      fixation for a unilateral fracture of the sustentaculum tali could be followed
      for a mean of 80 months (range 15-151 months). No wound healing problems or
      infections were seen with the medial approach. At the time of follow-up, 15
      sustentaculum tali fractures had an average Foot Function Index of 21.6 and an
      average AOFAS Ankle-Hindfoot Score of 83.6. Patients with isolated fractures of
      the sustentaculum tali had significantly better scores than those with additional
      injuries. In 1 patient, an additional lateral process fracture of the talus
      required subtalar fusion due to persistent pain. Care must be taken not to
      overlook these atypical calcaneal fractures and accompanying injuries to the mid
      tarsal joint and the lateral talar process as seen in 45% and 23%, respectively,
      in the present series.

PMID- 24306048
TI  - [Fractures of the anterior process of the calcaneus].
AB  - OBJECTIVE: Anatomical repositioning of isolated fractures of the anterior process
      of the calcaneus. Internal fixation for sufficiently large fragment sizes, for
      small fragments and evidence of instability of the calcaneocuboid (CC) joint in
      association with Chopart luxation fractures, transfixation of the CC joint.
      INDICATIONS: Dislocated fragments and intra-articular fractures (contraindication
      to open repositing: critical soft tissue relationships) and temporary
      stabilization for Chopart luxation fractures. CONTRAINDICATIONS: Infections and
      peripheral arterial occlusive disease (pAOD). SURGICAL TECHNIQUE: Supine position
      especially with accompanying injuries or placing in a side position for isolated
      fractures. Anterolateral access, fine repositioning by manipulation of the
      fragments with Kirschner wires, control of joint repositioning, definitive
      internal fixation with small fragments or miniscrews. For fragments not to be
      addressed, resection if necessary and transfixation with Kirschner wires.
      POSTOPERATIVE MANAGEMENT: Movement exercises of the ankle joint from
      postoperative day 1. From day 2 mobilization with partial loading of the affected
      leg with 20 kg for 6-8 weeks. After transfixation, removal of the wires after 6
      weeks and gradually increased loading. After subsidence of postoperative edema,
      patients can wear their own shoes or if necessary use a walker. RESULTS: Isolated
      fractures of the the anterior process of the calcaneus are rare and often
      initially overlooked injuries of the foot. In the literature there are only few
      case descriptions. From November 2009 to June 2011 a total of 5 isolated
      dislocated fractures of the anterior process with large fragments (type III), of
      which 3 were initially overlooked, were treated by osteosynthesis. In all cases
      the exact diagnosis could only be confirmed by computed tomography. In the follow
      up after 2 years and 5 months all patients showed consolidation of the fractures,
      especially those with delayed therapy. Clinically all patients had recovered full
      function with no evidence of posttraumatic arthrosis. In this small case series
      extended diagnostics in cases of suitable fracture mechanisms seems to be
      reasonable in order not to overlook rare fractures of the calcaneus. Operative
      therapy by anatomical repositioning and internal fixation of fractures of the
      anterior process of the calcaneus is a suitable therapy for treatment of these
      rare injuries.

PMID- 24306049
TI  - [Ankle arthrodesis with an posterolateral approach using a polyaxial angle stable
      Talarlock(r) plate].
AB  - OBJECTIVE: Safe arthrodesis of the ankle as well as load carrying capacity free
      of pain. INDICATION: Painful arthritis of the ankle joint occurring idiopathic or
      posttraumatic, resulting from rheumatoid arthritis or neuromuscular diseases.
      Extensive bony defects in varus or valgus ankle deformities and after failed
      prosthesis. Complex hindfoot deformities in neurological disease, paralysis and
      instabilities. Joint destruction after infection. CONTRAINDICATIONS: Active
      osteitis, extensive skin ulcers in the approach area, periphery artery occlusive
      disease. SURGICAL TECHNIQUE: Posterolateral skin incision. Sparing cartilage
      resection. Penetrating sclerosis zones. Reorientating anatomic positioning of the
      talus thereby correcting axis deformities. Talarlock((r)) plate positioning and
      tibiotalar arthrodesis. POSTOPERATIVE MANAGEMENT: Full weight bearing in an
      arthodesis boot for 6 weeks. After bone grafting partial weight bearing (20 kg)
      in an arthrodesis boot for 8 weeks. Full weight bearing after 10weeks. RESULTS:
      Ten patients were operated on using this procedure. The follow-up time was 1
      year. There were no complications requiring further surgical procedures. Ankle
      fusion and a good clinical outcome could be achieved in all cases.

PMID- 24306051
TI  - [Hindfoot fractures].

PMID- 24306050
TI  - [Medial closing wedge osteotomy for correction of genu valgum and torsional
      malalignment].
AB  - OBJECTIVE: Femoral medial closing wedge osteotomy for the correction of valgus
      malalignment to unload the cartilage in the lateral compartment and/or correction
      of symptomatic torsional malalignment. INDICATIONS: Lateral unicompartmental
      osteoarthritis of the knee with genu valgum in young patients. Symptomatic
      torsional malalignement of > 30 degrees  and < 0 degrees . CONTRAINDICATIONS:
      Grade 3 and 4 cartilage damage in the medial compartment. Heavy smoking. Medial
      meniscectomy. Extreme obesity. Inadequate soft tissue conditions. SURGICAL
      TECHNIQUE: The operation begins with arthroscopy of the knee joint. In case of
      grade 4 lateral cartilage damage, a microfracture is performed. The distal femur
      is exposed via an anteromedial longitudinal incision starting 10 cm above the
      patella and ending in the upper third of the patella. The medial femoral cortex
      is exposed using Hohmann retractors and an oblique closing wedge osteotomy is
      performed with an oscillating saw. In case of valgus correction, the lateral
      cortex is left intact. In case of correction of torsional malalignment, the
      osteotomy plane is horizontal and the lateral cortex is cut. The wedge height is
      determined preoperatively based on full leg x-rays. The leg axis is controlled
      intraoperatively with a long metal rod and the use of an image intensifier. The
      osteotomy is manually closed and stabilized with a locking plate. POSTOPERATIVE
      MANAGEMENT: The patient is mobilized under load with 20 kg body weight for the
      first 6 postoperative weeks. Full range of motion is permitted. RESULTS: We
      treated 23 patients with lateral cartilage damage (grades 3 and 4) and genu
      valgum with medial closing osteotomy of the distal femur (6 men and 17 women).
      After 3.5-years follow-up, the KOOS increased from 48.4 points to 84.9 points. In
      one case, there was an early loss of correction, with subsequent revision with
      bone grafting and lateral osteosynthesis. No peri-or postoperative complications
      such as infection, thrombosis, and embolism occurred. In 5 cases a torsional
      osteotomy was performed. The torsional osteotomy was performed 4 times due to
      chronic patellofemoral instability, and once due to a medial tibiofemoral
      instability. Healing complications were not observed in this population.
      Recurrent instability was not observed.

PMID- 24306053
TI  - Radiographic, SPECT, and echocardiographic presentation of cardiac pseudoaneurysm
      and 1 year follow-up.

PMID- 24306052
TI  - The importance of trabecular hypertrophy in right ventricular adaptation to
      chronic pressure overload.
AB  - To assess the contribution of right ventricular (RV) trabeculae and papillary
      muscles (TPM) to RV mass and volumes in controls and patients with pulmonary
      arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar
      response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP)
      during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and
      right heart catheterization at baseline and after one-year follow-up. Furthermore
      20 controls underwent CMR. RV masses were assessed with and without TPM. TPM
      constituted a larger proportion of total RV mass and RV end-diastolic volume
      (RVEDV) in PAH than in controls (Mass: 35 +/- 7 vs. 25 +/- 5 %; p < 0.001; RVEDV:
      17 +/- 6 vs. 12 +/- 6 %; p = 0.003). TPM mass was related to the RVFW mass in
      patients (baseline: R = 0.65; p < 0.001; follow-up: R = 0.80; p < 0.001) and
      controls (R = 0.76; p < 0.001). In PAH and controls, exclusion of TPM from the
      assessment resulted in altered RV mass, volumes and function than when included
      (all p < 0.01). Changes in RV TPM mass (beta = 0.44; p = 0.004) but not the
      changes in RVFW mass (p = 0.095) were independently related to changes in PAP
      during follow-up. RV TPM showed a larger contribution to total RV mass in PAH
      (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses
      significantly influenced the magnitude of the RV volumes and mass. Furthermore,
      TPM mass was stronger related to changes in PAP than RVFW mass. Our results
      implicate that TPM are important contributors to RV adaptation during pressure
      overload and cannot be neglected from the RV assessment.

PMID- 24306054
TI  - Sizing the mitral annulus in healthy subjects and patients with mitral
      regurgitation: 2D versus 3D measurements from cardiac CT.
AB  - The purpose of our study was (1) to assess retrospectively, in healthy subjects
      and in patients with moderate and severe functional mitral regurgitation (FMR),
      the normal mitral annular dimensions, (2) to determine differences in mitral
      annular geometry between healthy subjects and patients with FMR, and (3) to
      evaluate potential errors in 2-dimensional (2D) measurements given the 3D nature
      of the mitral annulus. 15 patients with no cardiac abnormalities (referred to as
      normals), 13 with moderate and 15 with severe FMR as determined by
      echocardiography underwent contrast-enhanced cardiac 64-slice Computed tomography
      (CT) with prospective electrocardiography-gating for excluding coronary artery
      disease. With an advanced visualization, segmentation, and image analysis
      software, the area, intercommissural distance (CC), septolateral distance (SLD),
      and the anterior and posterior circumference of the MA were measured in diastole.
      We found significant (P < .001) differences between normals and patients with
      severe FMR for area, SLD and posterior circumference in 3D (P < .001) and 2D (P <
      .001). Similarly, the SLD and the posterior circumference in both 3D (P = .002)
      and 2D (P = .001) were significantly smaller in patients with moderate FMR as
      compared to those with severe FMR. In contrast, there were no significant
      differences between groups regarding the CC and the anterior circumference both
      in 3D and 2D (all, P > .05). Measurements in 3D differed significantly from those
      with 2D for all circumference measurements and groups (P < .01), with a
      systematic underestimation of the posterior circumference of 2.1 +/- 1.5 mm in
      normals, 1.8 +/- 1.3 mm in patients with moderate FMR, and 1.9 +/- 1.9 mm in
      patients with severe FMR for 2D. Our study provides in vivo human CT data on MA
      dimensions in normals and patients with FMR, indicating differences in patients
      for the area, posterior circumference and SLD but not for the anterior
      circumference and CC. Systematic differences exist between 2D and 3D measurements
      for all circumferential measurements.

PMID- 24306055
TI  - Facile synthesis of mesoporous spinel NiCo2O4 nanostructures as highly efficient
      electrocatalysts for urea electro-oxidation.
AB  - Mesoporous spinel nickel cobaltite (NiCo2O4) nanostructures were synthesized via
      a facile chemical deposition method coupled with a simple post-annealing process.
      The physicochemical properties were characterized via X-ray diffraction (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      photoelectron spectra (XPS) and nitrogen sorption measurements. The
      electrocatalytic performances were investigated by cyclic voltammetry (CV),
      chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS) tests.
      The obtained NiCo2O4 materials exhibit typical agglomerate mesoporous
      nanostructures with a large surface area (190.1 m(2) g(-1)) and high mesopore
      volume (0.943 cm(3) g(-1)). Remarkably, the NiCo2O4 shows much higher catalytic
      activity, lower overpotential, better stability and greater tolerance towards
      urea electro-oxidation compared to those of cobalt oxide (Co3O4) synthesized by
      the same procedure. The NiCo2O4 electrode delivers a current density of 136 mA
      cm(-2) mg(-1) at 0.7 V (vs. Hg/HgO) in 1 M KOH and 0.33 M urea electrolytes
      accompanied with a desirable stability. The impressive electrocatalytic activity
      is largely ascribed to the high intrinsic electronic conductivity, superior
      mesoporous nanostructures and rich surface Ni active species of the NiCo2O4
      materials, which can largely boost the interfacial electroactive sites and charge
      transfer rates for urea electro-oxidation, indicating promising applications in
      future wastewater remediation, hydrogen production and fuel cells.

PMID- 24306056
TI  - Procalcitonin in febrile neutropenia--timing is important.

PMID- 24306057
TI  - Non-invasive measurement of transparency, arcus senilis, and scleral rim diameter
      of corneas during eye banking.
AB  - We developed a non-invasive device to quantify transparency (T), clear corneal
      diameter (CCD) excluding arcus senilis, and scleral rim diameter (SRD) of stored
      corneas. The T value (expressed in % on a relative scale), based on the
      modulation transfer function principle, referred to the ratio of local contrasts
      of a special LED backlit chart measured with and without cornea. CCD and SRD (in
      mm) were automatically calculated by morphologic operations. Firstly, we assessed
      measurement reproducibility. We then determined the agreement of T and CCD values
      with 3-level scores given independently by three experts on 179 scientific
      corneas. Thirdly, an eye bank was equipped with the device, and 358 consecutive
      organ-cultured (OC) corneas were tested for donor- and storage- related factors
      possibly influencing T and CCD. Reproducibility of T, CCD and SRD measurements
      was high, with intraclass correlation coefficients of 0.982, 0.886, and 0.999
      respectively. Capacity to discriminate the three levels of transparency and arcus
      senilis was good, with T of 20.0 (10.0-33.6), 38.3 (24.3-75.4) and 57.9 (33.9
      90.0) % respectively for T deemed poor, average, and good (P < 0.001), and CCD of
      9.8 (7.3-10.6), 10.5 (8.2-11.5), and 11.1 (9.9-12.0) mm respectively for arcus
      senilis deemed prominent, moderate or absent (P < 0.001). T was correlated with
      neither donor age nor endothelial cell density nor storage time, but slightly
      worsened during OC for corneas assessed twice. In conclusion, the device, which
      can be easily integrated in the facilities of an eye bank, provides reliable
      objective measurement of T, CCD, and SRD. This could be a useful tool for
      standardizing quality assessment of stored corneas and consequently optimizing
      their selection for penetrating, endothelial or anterior lamellar keratoplasty.

PMID- 24306058
TI  - Apathy and associated factors in Mexican patients with Parkinson's disease.
AB  - Apathy is one of the most common behavioral disturbances in Parkinson's disease
      (PD) with a reported prevalence of 17-51 %. Apathy has been associated with
      depression, cognitive deficits, and poor quality of life. The objective of this
      study was to determine the prevalence of apathy in Mexican subjects with PD and
      its correlation with clinical and demographic characteristics. A cross-sectional,
      descriptive, and analytic study was carried out. Consecutive subjects with PD
      attending the National Institute of Neurology and Neurosurgery in Mexico City
      were included. Demographic and other relevant clinical data were collected. The
      Apathy Scale was applied to all subjects. A cut-off score of >= 14 was used. A
      total of 241 non-demented patients (52.7 % male) were included. Apathy was found
      in 43 % of subjects. Lower body mass index, older age of PD onset, cognitive
      decline and disease severity were all related to apathy. The use of dopamine
      agonists or rasagiline was more common in patients with low apathy scores. Our
      results show that the prevalence of apathy in Mexican subjects with PD is similar
      to other reports.

PMID- 24306060
TI  - Nitrogen doped porous carbon fibres as anode materials for sodium ion batteries
      with excellent rate performance.
AB  - Nitrogen-doped activated porous carbon fibres (ACFs) were prepared as anode
      materials for Na-ion batteries. They exhibit excellent electrochemical
      performance, especially rate performance. The excellent rate performance is
      ascribed to the fibre-like morphology and the facilitated charge transfer. The
      influence of nitrogen functionalities on charge transfer and electrochemical
      performance of N-doped carbon anodes for Na ion batteries is discussed. 

PMID- 24306059
TI  - Protective mechanisms of adenosine 5'-monophosphate in platelet activation and
      thrombus formation.
AB  - Platelet activation is relevant to a variety of acute thrombotic events. We
      sought to examine adenosine 5'-monophosphate (AMP) mechanisms of action in
      preventing platelet activation, thrombus formation and platelet-related
      inflammatory response. We assessed the effect of AMP on 1) P-selectin expression
      and GPIIb/IIIa activation by flow cytometry; 2) Platelet aggregation and ATP
      secretion induced by ADP, collagen, TRAP-6, convulxin and thrombin; 3) Platelet
      rolling and firm adhesion, and platelet-leukocyte interactions under flow
      controlled conditions; and, 4) Platelet cAMP levels, sP-selectin, sCD40L, IL
      1beta, TGF-beta1 and CCL5 release, PDE3A activity and PKA phosphorylation. The
      effect of AMP on in vivo thrombus formation was also evaluated in a murine model.
      The AMP docking with respect to A2 adenosine receptor was determined by homology.
      AMP concentration-dependently (0.1 to 3 mmol/l) inhibited P-selectin expression
      and GPIIb/IIIa activation, platelet secretion and aggregation induced by ADP,
      collagen, TRAP-6 and convulxin, and diminished platelet rolling and firm
      adhesion. Furthermore, AMP induced a marked increase in the rolling speed of
      leukocytes retained on the platelet surface. At these concentrations AMP
      significantly decreased inflammatory mediator from platelet, increased
      intraplatelet cAMP levels and inhibited PDE3A activity. Interestingly, SQ22536,
      ZM241385 and SCH58261 attenuated the antiplatelet effect of AMP. Docking
      experiments revealed that AMP had the same orientation that adenosine inside the
      A2 adenosine receptor binding pocket. These in vitro antithrombotic properties
      were further supported in an in vivo model of thrombosis. Considering the
      successful use of combined antiplatelet therapy, AMP may be further developed as
      a novel antiplatelet agent. 

PMID- 24306061
TI  - Classification using sparse representations: a biologically plausible approach.
AB  - Representing signals as linear combinations of basis vectors sparsely selected
      from an overcomplete dictionary has proven to be advantageous for many
      applications in pattern recognition, machine learning, signal processing, and
      computer vision. While this approach was originally inspired by insights into
      cortical information processing, biologically plausible approaches have been
      limited to exploring the functionality of early sensory processing in the brain,
      while more practical applications have employed non-biologically plausible sparse
      coding algorithms. Here, a biologically plausible algorithm is proposed that can
      be applied to practical problems. This algorithm is evaluated using standard
      benchmark tasks in the domain of pattern classification, and its performance is
      compared to a wide range of alternative algorithms that are widely used in signal
      and image processing. The results show that for the classification tasks
      performed here, the proposed method is competitive with the best of the
      alternative algorithms that have been evaluated. This demonstrates that
      classification using sparse representations can be performed in a neurally
      plausible manner, and hence, that this mechanism of classification might be
      exploited by the brain. 

PMID- 24306062
TI  - Preoperative chemoradiation with or without induction oxaliplatin plus 5
      fluorouracil in locally advanced rectal cancer. Long-term outcome analysis.
AB  - BACKGROUND AND PURPOSE: It has been previously reported that a short FOLFOX-4
      induction significantly improves pathologic complete response in locally advanced
      rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In
      a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of
      sphincter preservation and long-term outcomes. PATIENTS AND METHODS: From January
      1995 to December 2010, 335 LARC patients were treated with preoperative
      chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients
      additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3
      12 weeks) after chemoradiation. RESULTS: Incidence of total tumor (63 vs. 54 %, p
      = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly
      increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from
      the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in
      the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up
      time for the entire cohort of patients was 72.6 months (range 4-205 months).
      FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p =
      0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free
      survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15).
      CONCLUSION: Short-intense induction FOLFOX-4 significantly improves downstaging
      and sphincter preservation in low rectal tumors. Long-term outcomes were not
      improved in the FOLFOX-4 group of patients.

PMID- 24306063
TI  - Whole abdominopelvic radiotherapy in the palliative treatment of pseudomyxoma
      peritonei.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical syndrome
      characterized by mucinous peritoneal disease arising from disseminated peritoneal
      adenomucinosis. Primary treatment involves a combination of cytoreductive surgery
      with hyperthermic intraperitoneal chemotherapy (HIPEC). There is no consensus on
      the proper treatment of recurrent PMP. In selected patients, repeated
      cytoreductive surgery with or without HIPEC might improve outcome. However, every
      repeated debulking procedure becomes less effective with increased morbidity.
      CASE REPORT: We present a case of a patient with intestinal obstruction caused by
      recurrent pseudomyxoma peritonei. We treated the patient with whole
      abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy (IMAT)
      to a total dose of 33 Gy, delivered in 22 daily fractions. The treatment was well
      tolerated and resulted in resolution of the obstruction for a period of 24
      months. CONCLUSION: To the best of our knowledge, we present the first case
      report showing the possibility of resolving intestinal obstruction with WAPRT in
      a patient with recurrent PMP. It is our opinion that WAPRT delivered by IMAT, in
      analogy with ovarian cancer, should be considered as a palliative treatment
      option in managing patients with recurrent PMP especially in case of obstruction.

PMID- 24306064
TI  - External-beam radiation therapy after surgical resection and intraoperative
      electron-beam radiation therapy for oligorecurrent gynecological cancer. Long
      term outcome.
AB  - PURPOSE: The goal of the present study was to analyze prognostic factors in
      patients treated with external-beam radiation therapy (EBRT), surgical resection
      and intraoperative electron-beam radiotherapy (IOERT) for oligorecurrent
      gynecological cancer (ORGC). PATIENTS AND METHODS: From January 1995 to December
      2012, 61 patients with ORGC [uterine cervix (52 %), endometrial (30 %), ovarian
      (15 %), vagina (3 %)] underwent IOERT (12.5 Gy, range 10-15 Gy), and surgical
      resection to the pelvic (57 %) and paraaortic (43 %) recurrence tumor bed. In
      addition, 29 patients (48 %) also received EBRT (range 30.6-50.4 Gy). Survival
      outcomes were estimated using the Kaplan-Meier method, and risk factors were
      identified by univariate and multivariate analyses. RESULTS: Median follow-up
      time for the entire cohort of patients was 42 months (range 2-169 months). The 10
      year rates for overall survival (OS) and locoregional control (LRC) were 17 and
      65 %, respectively. On multivariate analysis, no tumor fragmentation (HR 0.22; p
      = 0.03), time interval from primary tumor diagnosis to locoregional recurrence
      (LRR) < 24 months (HR 4.02; p = 0.02) and no EBRT at the time of pelvic
      recurrence (HR 3.95; p = 0.02) retained significance with regard to LRR. Time
      interval from primary tumor to LRR < 24 months (HR 2.32; p = 0.02) and no EBRT at
      the time of pelvic recurrence (HR 3.77; p = 0.04) showed a significant
      association with OS after adjustment for other covariates. CONCLUSION: External
      beam radiation therapy at the time of pelvic recurrence, time interval for
      relapse >= 24 months and not multi-involved fragmented resection specimens are
      associated with improved LRC in patients with ORGC. As suggested from the present
      analysis a significant group of ORGC patients could potentially benefit from
      multimodality rescue treatment.

PMID- 24306065
TI  - Effects of chemotherapy on the parotid and submandibular glands in head and neck
      cancer patients treated with chemoradiotherapy.

PMID- 24306066
TI  - [The chemotherapy before or after radiation therapy does not influence survival
      of children with high-risk medulloblastomas: results of the multicenter and
      randomized study of the Pediatric Oncology Group (POG 9031)].

PMID- 24306067
TI  - [Reduced acute toxicity for adults with medulloblastoma treated with proton beam
      craniospinal irradiation].

PMID- 24306069
TI  - Signs of the times.

PMID- 24306070
TI  - The placebo and the therapeutic uses of faith.
AB  - The holistic movement in modern medicine has raised questions concerning the very
      character of the religion-medicine dialogue. A truly mutual interaction between
      theology and medicine must require of the theologian a serious interest in and
      understanding of medicine if the notion of the body-mind unity is to be taken
      seriously from the point of view of pastoral care. This paper suggests that this
      discussion may be enriched by a theological analysis of the placebo, which has
      lately been the subject of controversy within medical circles. Finally, it is
      suggested that the value of the placebo reposes in its serving as a symbol of the
      dynamics of faith in medical care. 

PMID- 24306068
TI  - DEGRO practical guidelines: radiotherapy of breast cancer II: radiotherapy of non
      invasive neoplasia of the breast.
AB  - PURPOSE: To complement and update the 2007 practice guidelines of the breast
      cancer expert panel of the German Society of Radiation Oncology (DEGRO) for
      radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in
      the current version, a separate paper is dedicated to non-invasive proliferating
      epithelial neoplasia of the breast. In addition to the more general statements of
      the German interdisciplinary S3 guidelines, this paper is especially focused on
      indication and technique of RT in addition to breast conserving surgery. METHODS:
      The DEGRO expert panel performed a comprehensive survey of the literature
      comprising recently published data from clinical controlled trials, systematic
      reviews as well as meta-analyses, referring to the criteria of evidence-based
      medicine yielding new aspects compared to 2005 and 2007. The literature search
      encompassed the period 2008 to September 2012 using databases of PubMed and
      Guidelines International Network (G-I-N). Search terms were "non invasive breast
      cancer", "ductal carcinoma in situ, "dcis", "borderline breast lesions", "lobular
      neoplasia", "radiotherapy" and "radiation therapy". In addition to the more
      general statements of the German interdisciplinary S3 guidelines, this paper is
      especially focused on indications of RT and decision making of non-invasive
      neoplasia of the breast after surgery, especially ductal carcinoma in situ.
      RESULTS: Among different non-invasive neoplasia of the breast only the subgroup
      of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia,
      DIN) is considered for further recurrence risk reduction treatment modalities
      after complete excision of DCIS, particularly RT following breast conserving
      surgery (BCS), in order to avoid a mastectomy. About half of recurrences are
      invasive cancers. Up to 50 % of all recurrences require salvage mastectomy.
      Randomized clinical trials and a huge number of mostly observational studies have
      unanimously demonstrated that RT significantly reduces recurrence risks of
      ipsilateral DCIS as well as invasive breast cancer independent of patient age in
      all subgroups. The recommended total dose is 50 Gy administered as whole breast
      irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly.
      Retrospective data indicate a possible beneficial effect of an additional tumor
      bed boost for younger patients. Prospective clinical trials of different dose
      volume concepts (hypofractionation, accelerated partial breast irradiation, boost
      radiotherapy) are still ongoing. CONCLUSION: Postoperative radiotherapy permits
      breast conservation for the majority of women by halving local recurrence as well
      as reducing progression rates into invasive cancer. New data confirmed this
      effect in all patient subsets-even in low risk subgroups (LoE 1a).

PMID- 24306071
TI  - Meaning in life: Discovered or created?
AB  - Against the background claims that a meaningful life is more likely to be the
      product of creation than discovery and that a meaningful life must involve both
      subjective satisfaction and an objective moral component, three foundations of a
      meaningful life are discussed. These include the quality of one's relationships,
      the integrative power of one's goals and projects, and the role of story or
      stories. Concerning the role of story, the theological challenge is to choose
      that story or those stories that place life in a genuinely ultimate context. 

PMID- 24306072
TI  - A voice within: The prophetic experience of vocation.

PMID- 24306073
TI  - Masturbation from judaism to victorianism.
AB  - This article demonstrates how masturbation, based on a misconception of Genesis
      38:7-10, was judged harshly in both Judaism and Christianity, laying the
      foundation historically for social and religious hostility toward sex.
      Masturbation, known as the "secret sin," a threat to the human race, and an ontic
      evil, was condemned officially in 1054 by Pope Leo IX.From the medieval era to
      Victorianism there evolved new distortions of religion and science, so that
      masturbation was regarded as unnatural sex, murder, a diabolical practice, and
      the cause of two-thirds of all diseases and disorders including insanity,
      neurosis, and neurasthenia. Masturbation has historically served as the catalyst
      for social change in sexual attitudes. 

PMID- 24306074
TI  - Spiritual well-being in older adults: Harmonious interconnectedness.
AB  - The current study was designed to identify indicators of spiritual well-being in
      persons 65 years of age and over, using a grounded theory approach through the
      constant comparative method of data analysis. The basic social process of
      harmonious interconnectedness was discovered. This process was the unifying force
      between categories and within each identified category. The study has
      implications for health care personnel in that it provides a basis for assessing
      spiritual well-being in patients. 

PMID- 24306075
TI  - Mary, dogma, and psychoanalysis.
AB  - Why does Mary hold her prominent place in Catholic theology to the extent that
      five specific dogmas have developed around her? Psychoanalytic theory suggests
      dogma arises out of the psychic needs of people and psychic needs of people are
      expressed in dogma. The early views of Erich Fromm, a disciple of Freud, are
      presented to demonstrate that Marian dogma arose from the psychic needs of the
      people. The views of both Catholic and Protestant thinkers are presented, as well
      as theological and psychiatric views. 

PMID- 24306076
TI  - Staff support services: Room by the side of the road.
AB  - Staff Support Services, as done at Emory University Hospital, Atlanta, Georgia,
      uses the neutrality of the Department of Pastoral Services to meet the support
      needs of its staff. This model has evolved out of the concern of many departments
      to centralize and symbolize the availability of these various support services to
      hospital employees. Using a "shepherding model", Emory's Staff Support Services
      works both within and outside of the "room by he side of the road". 

PMID- 24306077
TI  - Inhibitory synapses between striatal projection neurons support efficient
      enhancement of cortical signals: a computational model.
AB  - The function of lateral inhibitory synapses between striatal projection neurons
      is currently poorly understood. This paper puts forward a model suggesting that
      inhibitory collaterals can be used to enhance the incoming cortical signals. In
      particular, we propose that lateral inhibition between projection neurons
      performs a signal-enhancing process that resembles the image processing technique
      of "unsharp masking", where a blurred copy is used to enhance and sharpen an
      input image. The paper also presents the results of computer simulations
      deomsntrating that the proposed mechanisms is compatible with known properties of
      striatal projection neurons, and outperforms alternative models of lateral
      inhibition. Finally, this paper illustrates the advantages of the proposed model
      and discusses the relevance of these conclusions for existing computational
      models of the basal ganglia and their role in cognition. 

PMID- 24306078
TI  - Copper-catalyzed trifluoromethylation of N-arylacrylamides "on water" at room
      temperature.
AB  - A copper-catalyzed intramolecular trifluoromethylation of arylacrylamides leads
      to oxindole derivatives, effected with stable and inexpensive Langlois' reagent
      (CF3SO2Na). These reactions proceed via a radical process in water at room
      temperature. The aqueous solution can be recycled. 

PMID- 24306079
TI  - Prognostic factors for mortality in (fecal) peritonitis: back to the roots!

PMID- 24306080
TI  - Patients with faecal peritonitis admitted to European intensive care units: an
      epidemiological survey of the GenOSept cohort.
AB  - INTRODUCTION: Faecal peritonitis (FP) is a common cause of sepsis and admission
      to the intensive care unit (ICU). The Genetics of Sepsis and Septic Shock in
      Europe (GenOSept) project is investigating the influence of genetic variation on
      the host response and outcomes in a large cohort of patients with sepsis admitted
      to ICUs across Europe. Here we report an epidemiological survey of the subset of
      patients with FP. OBJECTIVES: To define the clinical characteristics, outcomes
      and risk factors for mortality in patients with FP admitted to ICUs across
      Europe. METHODS: Data was extracted from electronic case report forms. Phenotypic
      data was recorded using a detailed, quality-assured clinical database. The
      primary outcome measure was 6-month mortality. Patients were followed for 6
      months. Kaplan-Meier analysis was used to determine mortality rates. Cox
      proportional hazards regression analysis was employed to identify independent
      risk factors for mortality. RESULTS: Data for 977 FP patients admitted to 102
      centres across 16 countries between 29 September 2005 and 5 January 2011 was
      extracted. The median age was 69.2 years (IQR 58.3-77.1), with a male
      preponderance (54.3%). The most common causes of FP were perforated diverticular
      disease (32.1%) and surgical anastomotic breakdown (31.1%). The ICU mortality
      rate at 28 days was 19.1%, increasing to 31.6% at 6 months. The cause of FP, pre
      existing co-morbidities and time from estimated onset of symptoms to surgery did
      not impact on survival. The strongest independent risk factors associated with an
      increased rate of death at 6 months included age, higher APACHE II score, acute
      renal and cardiovascular dysfunction within 1 week of admission to ICU,
      hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. CONCLUSIONS:
      In this large cohort of patients admitted to European ICUs with FP the 6 month
      mortality was 31.6%. The most consistent predictors of mortality across all time
      points were increased age, development of acute renal dysfunction during the
      first week of admission, lower haematocrit and hypothermia on day 1 of ICU
      admission.

PMID- 24306081
TI  - Influence of ventilatory strategy on the PRESERVE mortality risk score.

PMID- 24306082
TI  - Time course of central venous-to-arterial carbon dioxide tension difference in
      septic shock patients receiving incremental doses of dobutamine.
AB  - PURPOSE: To assess the time course of the central venous-arterial carbon dioxide
      tension difference (?PCO2)-as an index of the carbon dioxide production
      (VCO2)/cardiac index (CI) ratio-in stable septic shock patients receiving
      incremental doses of dobutamine. METHODS: Twenty-two hemodynamically stable
      septic shock patients with no signs of global tissue hypoxia, as testified by
      normal blood lactate levels, were prospectively included. A dobutamine infusion
      was administered at a dose of up to 15 MUg/kg/min in increments of 5 MUg/kg/min
      every 30 min. Complete hemodynamic and gas measurements were obtained at
      baseline, and at each dose of dobutamine. RESULTS: Dobutamine induced a
      significant dose-dependent increase of CI from 0 to 15 MUg/kg/min (P < 0.001).
      Oxygen consumption (VO2) and VCO2 were progressively increased by dobutamine.
      These increases were more marked between 10 and 15 MUg/kg/min (8.3 and 8.6 %,
      respectively) than between the lower doses. ?PCO2 and oxygen extraction (EO2)
      significantly decreased between 0 (8.0 +/- 2.0 mmHg and 43.8 +/- 13.4 %,
      respectively) and 10 MUg/kg/min of dobutamine (4.2 +/- 1.6 mmHg and 28.9 +/- 7.9
      %, respectively), but remained unchanged from 10 to 15 MUg/kg/min (5.4 +/- 2.4
      mmHg and 29.5 +/- 8.2 %, respectively). The central venous oxygen saturation
      significantly (ScvO2) increased from 0 to 10 MUg/kg/min and remained unchanged
      from 10 to 15 MUg/kg/min. Time courses of ?PCO2, ScvO2, and EO2 were linked
      therefore to the biphasic changes of VO2 and VCO2. CONCLUSION: ?PCO2 is a good
      indicator of the change of VCO2 induced by dobutamine. Measurement of ?PCO2,
      along with ScvO2 and EO2, may be presented as a useful tool to assess the
      adequacy of oxygen supply versus metabolic and oxygen demand.

PMID- 24306083
TI  - The utility of stroke volume variability as a predictor of fluid responsiveness
      in critically ill children: a pilot study.

PMID- 24306084
TI  - Thrombosis of the aortic root and ascending aorta during extracorporeal membrane
      oxygenation.

PMID- 24306085
TI  - Response to De Jonghe et al.: Prognostication of neurological outcome after
      cardiac arrest: standardization of neurological examination conditions is needed.

PMID- 24306086
TI  - Azygos vein enlargement and cavo-suprahepatic regurgitation in massive pulmonary
      embolism.

PMID- 24306087
TI  - Ultrasound-guided radial artery catheterization: a meta-analysis of randomized
      controlled trials.

PMID- 24306088
TI  - Long-term follow up of frontline therapy with fludarabine and cyclophosphamide in
      chronic lymphocytic leukemia: impact of biological parameters on clinical
      outcome.

PMID- 24306089
TI  - Eculizumab for the treatment of pregnancy-related atypical hemolytic uremic
      syndrome.

PMID- 24306090
TI  - A cascade reaction: ring-opening insertion of dioxaphospholane into lutetium
      alkyl bonds.
AB  - Geometrically constrained dioxaphospholane rings were incorporated into a
      bis(phosphinimine)carbazole ligand (HL) in an effort to generate an ancillary
      ligand system that is capable of supporting reactive lutetium alkyl
      functionalities and resistant to cyclometalation reactivity. This new ligand was
      used to prepare a lutetium dialkyl species, LLu(CH2SiMe3)2; however, the complex
      exhibited low thermal stability at ambient temperature. This dialkyl compound was
      found to be highly susceptible to a cascading inter- and intramolecular reaction
      that resulted in the sole formation of an asymmetric bimetallic tetraalkoxide
      complex. The product of this reaction, generated by the ring-opening insertion of
      dioxaphospholane moieties into lutetium-carbon bonds, was characterized by
      multinuclear NMR spectroscopy and single crystal X-ray diffraction. 

PMID- 24306092
TI  - A Novel Quinazolinone Derivative as Fluorescence Quenching Off-On Sensor for High
      Selectivity of Fe(3+).
AB  - A novel quinazolinone compound containing quinazoline-fused moiety has been
      synthesized as fluorescence Off-On sensor QQ. The probe exhibited highly
      selective and sensitive recognition toward trivalent ferric ion (Fe(3+)) over
      other metal ions in HEPES buffer solution (10 mM, pH = 7.0, DMF-H2O, 9:1, v/v).
      The significant quenching in the fluorescence spectral could be served as a
      selective fluorescence Off-On sensor. The titration study indicated the formation
      of 1:1 complex between QQ and Fe(3+). 

PMID- 24306091
TI  - Disruption of cortical association networks in schizophrenia and psychotic
      bipolar disorder.
AB  - IMPORTANCE: Psychotic disorders (including schizophrenia, schizoaffective
      disorder, and psychotic bipolar disorder) are devastating illnesses characterized
      by breakdown in the integration of information processing. Recent advances in
      neuroimaging allow for the estimation of brain networks on the basis of intrinsic
      functional connectivity, but the specific network abnormalities in psychotic
      disorders are poorly understood. OBJECTIVE: To compare intrinsic functional
      connectivity across the cerebral cortex in patients with schizophrenia spectrum
      disorders or psychotic bipolar disorder and healthy controls. DESIGN, SETTING,
      AND PARTICIPANTS: We studied 100 patients from an academic psychiatric hospital
      (28 patients with schizophrenia, 32 patients with schizoaffective disorder, and
      40 patients with bipolar disorder with psychosis) and 100 healthy controls
      matched for age, sex, race, handedness, and scan quality from December 2009 to
      October 2011. MAIN OUTCOMES AND MEASURES: Functional connectivity profiles across
      122 regions that covered the entire cerebral cortex. RESULTS: Relative to the
      healthy controls, individuals with a psychotic illness had disruption across
      several brain networks, with preferential reductions in functional connectivity
      within the frontoparietal control network (P < .05, corrected for family-wise
      error rate). This functionally defined network includes portions of the
      dorsolateral prefrontal cortex, posteromedial prefrontal cortex, lateral parietal
      cortex, and posterior temporal cortex. This effect was seen across diagnoses and
      persisted after matching patients and controls on the basis of scan quality.
      CONCLUSIONS AND RELEVANCE: Our study results support the view that cortical
      information processing is disrupted in psychosis and provides new evidence that
      disruptions within the frontoparietal control network may be a shared feature
      across both schizophrenia and affective psychosis.

PMID- 24306093
TI  - Intermediate doses of low-molecular-weight heparin for the long-term treatment of
      pregnancy thromboembolism. A systematic review.

PMID- 24306094
TI  - Prevalence of sexual abuse among children with conduct disorder: a systematic
      review.
AB  - Many clinicians and researchers have speculated that child sexual abuse and
      conduct disorder co-occur frequently, yet no systematic reviews of literature
      have specifically addressed both these conditions. To estimate the prevalence of
      sexual abuse among children with conduct disorder, the pertinent literature was
      systematically reviewed. Ten databases were searched, supplemented with hand
      search of reference lists from retrieved papers. Blind assessments of study
      eligibility and quality were conducted by two independent researchers.
      Disagreements were resolved by consensus. Twenty-three studies meeting minimum
      quality criteria that were enough to insure objectivity and not to invalidate
      results and including 7,256 participants with either conduct disorder or child
      sexual abuse were examined. The prevalence of child sexual abuse among
      participants with conduct disorder was 27 %; however, such figure might be
      underestimated due to selection, sampling, and recall biases; poor assessment
      methods; and narrow definitions of abuse in included studies. Participants with
      conduct disorder, compared with healthy individuals, reported higher rates of
      child sexual abuse. However, compared with other psychiatric populations, they
      reported similar or lower rates. There was also some evidence suggesting that
      children with conduct disorder might be more likely to report child physical
      abuse. Female participants with conduct disorder, compared with males, were
      significantly more likely to report child sexual abuse. Youths with conduct
      disorder are at risk of being (or having been) sexually abused, although such
      risk seems to be neither more specific to nor stronger for these individuals,
      compared with people with other psychiatric disorders.

PMID- 24306095
TI  - [Invasive candidiasis in non-neutropenic adults : Guideline-based management in
      the intensive care unit].
AB  - Invasive Candida infections represent a diagnostic and therapeutic challenge for
      clinicians particularly in the intensive care unit (ICU). Despite substantial
      advances in antifungal agents and treatment strategies, invasive candidiasis
      remains associated with a high mortality. Recent guideline recommendations on the
      management of invasive candidiasis by the European Society of Clinical
      Microbiology and Infectious Diseases (ESCMID) from 2012, the German Speaking
      Mycological Society and the Paul Ehrlich Society for Chemotherapy (DMykG/PEG)
      from 2011 and the Infectious Diseases Society of America (IDSA) from 2009 provide
      valuable guidance for diagnostic procedures and treatment of these infections but
      need to be interpreted in the light of the individual situation of the patient
      and the local epidemiology of fungal pathogens. The following recommendations for
      management of candidemia are common to all three guidelines. Any positive blood
      culture for Candida indicates disseminated infection or deep organ infection and
      requires antifungal therapy. Treatment should be initiated as soon as possible.
      Removal or changing of central venous catheters or other foreign material in the
      bloodstream is recommended whenever possible. Ophthalmological examination for
      exclusion of endophthalmitis and follow-up blood cultures during therapy are also
      recommended. Duration of therapy should be 14 days after clearance of blood
      cultures and resolution of symptoms. Consideration of surgical options and a
      prolonged antifungal treatment (weeks to months) are required when there is organ
      involvement. During the last decade several new antifungal agents were introduced
      into clinical practice. 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. Echinocandins have emerged as the generally
      preferred primary treatment in candidemia. The expert panel of ESCMID views
      fluconazole only as a marginally recommended therapy for this indication. The use
      of amphotericin B deoxycholate should be generally avoided because of toxicity. 

PMID- 24306096
TI  - [Ventilator-induced diaphragm dysfunction : clinically relevant problem].
AB  - Mechanical ventilation is a life-saving intervention for patients with
      respiratory failure or during deep sedation. During continuous mandatory
      ventilation the diaphragm remains inactive, which activates pathophysiological
      cascades leading to a loss of contractile force and muscle mass (collectively
      referred to as ventilator-induced diaphragm dysfunction, VIDD). In contrast to
      peripheral skeletal muscles this process is rapid and develops after as little as
      12 h and has a profound influence on weaning patients from mechanical ventilation
      as well as increased incidences of morbidity and mortality. In recent years,
      animal experiments have revealed pathophysiological mechanisms which have been
      confirmed in humans. One major mechanism is the mitochondrial generation of
      reactive oxygen species that have been shown to damage contractile proteins and
      facilitate protease activation. Besides atrophy due to inactivity, drug
      interactions can induce further muscle atrophy. Data from animal research
      concerning the influence of corticosteroids emphasize a dose-dependent influence
      on diaphragm atrophy and function although the clinical interpretation in
      intensive care patients (ICU) patients might be difficult. Levosimendan has also
      been proven to increase diaphragm contractile forces in humans which may prove to
      be helpful for patients experiencing difficult weaning. Additionally, antioxidant
      drugs that scavenge reactive oxygen species have been demonstrated to protect the
      diaphragm from VIDD in several animal studies. The translation of these drugs
      into the IUC setting might protect patients from VIDD and facilitate the weaning
      process. 

PMID- 24306097
TI  - Fitness cost associated with resistance to fluoroquinolones is diverse across
      clones of Klebsiella pneumoniae and may select for CTX-M-15 type extended
      spectrum beta-lactamase.
AB  - Lowered fitness cost associated with resistance to fluoroquinolones was recently
      demonstrated to influence the clonal dynamics of methicillin-resistant
      Staphylococcus aureus (MRSA) in the health care setting. We investigated whether
      or not a similar mechanism impacts Klebsiella pneumoniae. The fitness of K.
      pneumoniae isolates from major international hospital clones (ST11, ST15, ST147)
      already showing high-level resistance to fluoroquinolones and of strains from
      three minor clones (ST25, ST274, ST1028) in which fluoroquinolone resistance was
      induced in vitro was tested in a propagation assay. Strains from major clones
      showed significantly less fitness cost than three of four fluoroquinolone
      resistant derivatives of minor clone isolates. In addition, plasmids with CTX-M
      15 type extended-spectrum beta-lactamase (ESBL) genes were all retained in both
      major and minor clone isolates, irrespective of the strains' level of
      fluoroquinolone resistance, while each plasmid harboring SHV-type ESBLs had been
      lost during the induction of resistance. Major clone K. pneumoniae strains
      harbored more amino acid substitutions in the quinolone resistance determining
      regions (QRDRs) of the gyrA and parC genes than minor clone isolates. The
      presence of an active efflux system could be demonstrated in all fluoroquinolone
      resistant derivatives of originally SHV-producing minor clone isolates but not in
      any CTX-M-15-producing strain. Further investigations are needed to expand and
      confirm our findings on a larger sample. In addition, a long-term observation of
      our ciprofloxacin-resistant minor clone isolates is required in order to
      elucidate whether or not they are capable of restoring their fitness while
      concomitantly retaining high minimum inhibitory concentration (MIC) values. 

PMID- 24306098
TI  - Emergence of NDM-producing non-baumannii Acinetobacter spp. isolated from China.
AB  - One hundred and thirty-six bla OXA-51-negative strains were identified from 1,067
      Acinetobacter calcoaceticus-A. baumannii complex (ACB complex) isolates, which
      were collected during October 2010 to March 2013 from 15 general hospitals in 10
      cities throughout Zhejiang Province, China. Seven of the 136 bla OXA-51-negative
      ACB complex isolates were New Delhi metallo-beta-lactamase-1 (NDM-1)-positive,
      among which three were identified as A. nosocomialis and four were identified as
      A. pittii strains using 16S-23S rRNA gene intergenic spacer (ITS) sequencing and
      partial RNA polymerase beta-subunit (rpoB) sequencing. Pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST) analysis showed that
      the seven NDM-positive isolates belonged to three clonal strains with three novel
      sequence types (STs). Polymerase chain reaction (PCR) assays and DNA sequence
      analysis of the carbapenemase and other beta-lactamase genes indicated that all
      the isolates harbored the bla NDM-1 gene, and that only one strain of A.
      nosocomialis isolates harbored both bla NDM-1 and bla OXA-23. All of them were
      positive for bla ADC, from which three novel bla ADC genes (designated as bla ADC
      69, bla ADC-70, and bla ADC-71) were detected for the first time. The presence of
      ISAba125 upstream of bla NDM-1 was identified through genetic environment
      analysis. Carbapenem resistance can be transferred from A. nosocomialis and A.
      pittii to Escherichia coli EC600 by the conjugation experiment. Plasmid analysis,
      DNA hybridization, and extraction experiments indicated that bla NDM-1 was
      located on a plasmid of approximately 50 kb. In conclusion, we characterized the
      dissemination of NDM-1-positive A. pittii strains in Zhejiang Province, China,
      and reported the NDM-producing A. nosocomialis for the first time.

PMID- 24306099
TI  - Post-operative central nervous system infections after cranial surgery in China:
      incidence, causative agents, and risk factors in 1,470 patients.
AB  - A post-operative central nervous system infection (PCNSI) is a dangerous
      complication after cranial surgery. Although a large number of neurosurgical
      procedures are performed in hospitals in China, PCNSI-related data from this
      country are rarely reported. To address this issue, we examined the incidence of
      PCNSI after cranial surgery, the potential risk factors, and the offending
      etiologic agents in a large Chinese population. The medical records and post
      operative courses for patients >16 years of age who underwent elective or
      emergency cranial surgeries between May 2010 and May 2012 and who survived for >7
      days were reviewed retrospectively. Pre-operative data, surgery-related records,
      and post-operative variables were evaluated as risk factors for PCNSI after
      cranial surgery. Among 1,470 surgeries, 1,340 were craniotomies and 130 involved
      the cerebrospinal fluid (CSF). There were 109 patients with PCNSIs, resulting in
      a total infection rate of 7.4 %. The dominant Gram-positive organism isolated
      (Staphylococcus aureus) was the most common pathogen isolated. Based on
      multivariate analysis, the risk of PCNSI was increased by a CSF leak [odds ratio
      (OR), 3.545; 95 % confidence interval (CI), 2.053-6.122; p < 0.001], CSF drainage
      of any kind (OR, 2.858; 95 % CI, 1.577-5.181; p = 0.001), subsequent short-term
      surgery (OR, 2.224; 95 % CI, 1.229-4.024; p = 0.008), and surgery duration (OR,
      1.331; 95 % CI, 1.230-1.440; p < 0.001). PCNSI remains a critical problem for
      neurosurgeons in China. CSF leakage, CSF drainage of any kind, subsequent short
      term surgery, and surgery duration were major risk factors, indicating that
      surgery-focused management might be the most effective way to minimize the risk
      for PCNSI after cranial surgery.

PMID- 24306101
TI  - Formation of a pseudo-beta-hairpin motif utilizing the Ant-Pro reverse turn:
      consequences of stereochemical reordering.
AB  - Herein, we report a special case of pseudo-beta-hairpin formation by tetrapetide
      sequences featuring a two-membered Ant-Pro dipeptide motif (Ant = anthranilic
      acid and Pro = proline) at the loop region. These folded structures uniquely
      feature the presence of C9- and C17-H-bonding patterns at reverse turn and
      interstrand regions, respectively. Their hairpin nucleation and folding
      propensities have been expounded using solution and solid state studies of
      distinct stereochemically altered sequences. 

PMID- 24306100
TI  - Gastric sensitivity and reflexes: basic mechanisms underlying clinical problems.
AB  - Both reflex and sensory mechanisms control the function of the stomach, and
      disturbances in these mechanisms may explain the pathophysiology of disorders of
      gastric function. The objective of this report is to perform a literature-based
      critical analysis of new, relevant or conflicting information on gastric
      sensitivity and reflexes, with particular emphasis on the comprehensive
      integration of basic and clinical research data. The stomach exerts both phasic
      and tonic muscular (contractile and relaxatory) activity. Gastric tone determines
      the capacity of the stomach and mediates both gastric accommodation to a meal as
      well as gastric emptying, by partial relaxation or progressive recontraction,
      respectively. Perception and reflex afferent pathways from the stomach are
      activated independently by specific stimuli, suggesting that the terminal nerve
      endings operate as specialized receptors. Particularly, perception appears to be
      related to stimulation of tension receptors, while the existence of volume
      receptors in the stomach is uncertain. Reliable techniques have been developed to
      measure gastric perception and reflexes both in experimental and clinical
      conditions, and have facilitated the identification of abnormal responses in
      patients with gastric disorders. Gastroparesis is characterised by impaired
      gastric tone and contractility, whereas patients with functional dyspepsia have
      impaired accommodation, associated with antral distention and increased gastric
      sensitivity. An integrated view of fragmented knowledge allows the design of
      pathophysiological models in an attempt to explain disorders of gastric function,
      and may facilitate the development of mechanistically orientated treatments. 

PMID- 24306102
TI  - The relationship between male BMI and waist circumference on semen quality: data
      from the LIFE study.
AB  - STUDY QUESTION: What is the relationship between body size, physical activity and
      semen parameters among male partners of couples attempting to become pregnant?
      SUMMARY ANSWER: Overweight and obesity are associated with a higher prevalence of
      low ejaculate volume, sperm concentration and total sperm count. WHAT IS KNOWN
      ALREADY: Higher BMI is associated with impaired semen parameters, while
      increasing waist circumference (WC) is also associated with impaired semen
      parameters in infertile men. STUDY DESIGN, SIZE, DURATION: Data from the
      Longitudinal Investigation of Fertility and the Environment (LIFE) Study were
      utilized. The LIFE study is a population-based prospective cohort of 501 couples
      attempting to conceive in two geographic areas (Texas and Michigan, USA)
      recruited in 2005-2009. Couples were recruited from four counties in Michigan and
      12 counties in Texas to ensure a range of environmental exposures and lifestyle
      characteristics. In person interviews were conducted to ascertain demographic,
      health and reproductive histories followed by anthropometric assessment.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: We categorized BMI (kg/m(2)) as <25.0
      (underweight and normal), 25.0-29.9 (overweight) 30.0-34.9 (obese, class I) and
      >=35 (obese, class II) for analysis. Data were available for analysis in 468 men
      (93% participation), with a mean +/- SD age of 31.8 +/- 4.8 years, BMI of 29.8 +/
      5.6 kg/m(2) and WC of 100.8 +/- 14.2 cm. The majority of the cohort (82%) was
      overweight or obese with 58% reporting physical activity <1 time/week. The median
      sperm concentration for the men in the cohort was 60.2 M/ml with 8.6% having
      oligospermia (<15 M/ml). MAIN RESULTS AND THE ROLE OF CHANCE: When examining
      semen parameters, ejaculate volume showed a linear decline with increasing BMI
      and WC (P < 0.01). Similarly, the total sperm count showed a negative linear
      association with WC (P < 0.01). No significant relationship was seen between body
      size (i.e. BMI or WC) and semen concentration, motility, vitality, morphology or
      DNA fragmentation index. The percentage of men with abnormal volume,
      concentration and total sperm increased with increasing body size (P < 0.05). No
      relationship between physical activity and semen parameters was identified.
      LIMITATIONS, REASONS FOR CAUTION: Our cohort was largely overweight and
      sedentary, which may result in limited external validity, i.e. generalizability.
      The lack of physical activity did preclude examination of exercise more
      frequently than once per week, thus our ability to examine more active
      individuals is limited. WIDER IMPLICATIONS OF THE FINDINGS: Body size (as
      measured by BMI or WC) is negatively associated with semen parameters with little
      influence of physical activity. Our findings are the first showing a relationship
      between WC and semen parameters in a sample of men without known infertility.
      Given the worldwide obesity epidemic, further study of the role of weight loss to
      improve semen parameters is warranted. STUDY FUNDING/COMPETING INTEREST(S):
      Supported by the Intramural Research Program of the Eunice Kennedy Shriver
      National Institute of Child Health and Human Development (Contracts #N01-HD-3
      3355, N01-HD-3-3356 and N01-HD-3-3358). There are no competing interests.

PMID- 24306103
TI  - Classification of locoregional lymph nodes in medullary and papillary thyroid
      cancer.
AB  - BACKGROUND: Among the various thyroid malignancies, medullary and papillary
      thyroid carcinomas are characterized by predominant locoregional lymph node
      metastases that may cause morbidity and affect patient survival. Although lymph
      node metastases are frequently detected, the optimal strategy aiming at the
      removal of all tumor tissues while minimizing the associated surgical morbidity
      remains a matter of debate. PURPOSE: A uniform consented terminology and
      classification is a precondition in order to compare results of the surgical
      treatment of thyroid carcinomas. While the broad distinction between central and
      lateral lymph node groups is generally accepted, the exact boundaries of these
      neck regions vary significantly in the literature. Four different classification
      systems are currently used. The classification system of the American Head and
      Neck Society and the corresponding classification system of the Union for
      International Cancer Control (UICC) are based on observations of squamous cell
      carcinomas and appointed to needs of head and neck surgeons. The classification
      of the Japanese Society for Thyroid Diseases and the compartment classification
      acknowledge the distinctive pattern of metastasis in thyroid carcinomas.
      CONCLUSIONS: Comparison of four existing classification systems reveals
      underlying different treatment concepts. The compartment system meets the
      necessities of thyroid carcinomas and is used worldwide in studies describing the
      results of lymph node dissection. Therefore, the German Association of Endocrine
      Surgery has recommended using the latter system in their recently updated
      guidelines on thyroid carcinoma.

PMID- 24306104
TI  - Spontaneous and non-spontaneous bleeding complications in patients with oral
      vitamin K antagonist therapy.
AB  - PURPOSE: The aim of the study was to evaluate potential differences between
      patients with spontaneous and non-spontaneous bleeding episodes during treatment
      with vitamin K antagonists which mainly resulted in compartment syndromes.
      METHODS: The population in this study comprised 116 patients who suffered at
      least one bleeding complication which required surgical treatment during therapy
      with an oral vitamin K antagonist. The patients were treated between September
      2001 and July 2008. RESULTS: Significant differences were observed between the
      two patient groups with regard to the presence of renal failure, arterial
      hypertension, and diabetes mellitus, which occurred more frequently in patients
      with spontaneous bleeding. Also, significantly more patients with spontaneous
      bleedings developed compartment syndrome that needed emergency operation. Overall
      mortality was 9.6 %, was associated with multiorgan failure in all patients, and
      was not different between the two patient groups. CONCLUSIONS: The identification
      of high-risk patients before treatment with an oral vitamin K antagonist is of
      major importance. The existence of over-anticoagulation syndrome and compartment
      syndrome is associated with significant mortality and morbidity and should not be
      underestimated.

PMID- 24306105
TI  - Ion channels contribute to the regulation of cell sheet forces during Drosophila
      dorsal closure.
AB  - We demonstrate that ion channels contribute to the regulation of dorsal closure
      in Drosophila, a model system for cell sheet morphogenesis. We find that Ca(2+)
      is sufficient to cause cell contraction in dorsal closure tissues, as UV-mediated
      release of caged Ca(2+) leads to cell contraction. Furthermore, endogenous Ca(2+)
      fluxes correlate with cell contraction in the amnioserosa during closure, whereas
      the chelation of Ca(2+) slows closure. Microinjection of high concentrations of
      the peptide GsMTx4, which is a specific modulator of mechanically gated ion
      channel function, causes increases in cytoplasmic free Ca(2+) and actomyosin
      contractility and, in the long term, blocks closure in a dose-dependent manner.
      We identify two channel subunits, ripped pocket and dtrpA1 (TrpA1), that play a
      role in closure and other morphogenetic events. Blocking channels leads to
      defects in force generation via failure of actomyosin structures, and impairs the
      ability of tissues to regulate forces in response to laser microsurgery. Our
      results point to a key role for ion channels in closure, and suggest a mechanism
      for the coordination of force-producing cell behaviors across the embryo. 

PMID- 24306106
TI  - Drosophila intermediate neural progenitors produce lineage-dependent related
      series of diverse neurons.
AB  - Drosophila type II neuroblasts (NBs), like mammalian neural stem cells, deposit
      neurons through intermediate neural progenitors (INPs) that can each produce a
      series of neurons. Both type II NBs and INPs exhibit age-dependent expression of
      various transcription factors, potentially specifying an array of diverse neurons
      by combinatorial temporal patterning. Not knowing which mature neurons are made
      by specific INPs, however, conceals the actual variety of neuron types and limits
      further molecular studies. Here we mapped neurons derived from specific type II
      NB lineages and found that sibling INPs produced a morphologically similar but
      temporally regulated series of distinct neuron types. This suggests a common fate
      diversification program operating within each INP that is modulated by NB age to
      generate slightly different sets of diverse neurons based on the INP birth order.
      Analogous mechanisms might underlie the expansion of neuron diversity via INPs in
      mammalian brain. 

PMID- 24306107
TI  - Involvement of Delta/Notch signaling in zebrafish adult pigment stripe
      patterning.
AB  - The skin pigment pattern of zebrafish is a good model system in which to study
      the mechanism of biological pattern formation. Although it is known that
      interactions between melanophores and xanthophores play a key role in the
      formation of adult pigment stripes, molecular mechanisms for these interactions
      remain largely unknown. Here, we show that Delta/Notch signaling contributes to
      these interactions. Ablation of xanthophores in yellow stripes induced the death
      of melanophores in black stripes, suggesting that melanophores require a survival
      signal from distant xanthophores. We found that deltaC and notch1a were expressed
      by xanthophores and melanophores, respectively. Moreover, inhibition of
      Delta/Notch signaling killed melanophores, whereas activation of Delta/Notch
      signaling ectopically in melanophores rescued the survival of these cells, both
      in the context of pharmacological inhibition of Delta/Notch signaling and after
      ablation of xanthophores. Finally, we showed by in vivo imaging of cell membranes
      that melanophores extend long projections towards xanthophores in the yellow
      stripes. These data suggest that Delta/Notch signaling is responsible for a
      survival signal provided by xanthophores to melanophores. As cellular projections
      can enable long-range interaction between membrane-bound ligands and their
      receptors, we propose that such projections, combined with direct cell-cell
      contacts, can substitute for the effect of a diffusible factor that would be
      expected by the conventional reaction-diffusion (Turing) model. 

PMID- 24306109
TI  - A novel method for bone area measurement provides new insights into
      osteoarthritis and its progression.
AB  - BACKGROUND: Modern image analysis enables the accurate quantification of knee
      osteoarthritis (OA) bone using MRI. We hypothesised that three-dimensional
      changes in bone would be characteristic of OA and provide a responsive measure of
      progression. METHODS: 1312 participants with radiographic knee OA, and 885 non-OA
      controls with MRIs at baseline, 1, 2 and 4 years were selected from the NIH
      Osteoarthritis Initiative. Automated segmentation of all knee bones and
      calculation of bone area was performed using active appearance models. In a
      subset of 352 participants, responsiveness of bone area change was compared with
      change in radiographic joint space width (JSW) and MRI cartilage thickness over a
      2-year period. RESULTS: All OA knee compartments showed increased bone area over
      time compared with non-OA participants: for example, the 4-year percentage change
      from baseline in medial femur area for OA (95% CI) was 1.87(0.13), non-OA 0.43
      (0.07); p<0.0001. Bone area change was more responsive than cartilage thickness
      or JSW; 2-year SRM for bone area in the medial femur was 0.83, for the most
      responsive cartilage thickness measure central medial femorotibial composite
      (cMFTC): 0.38, JSW: 0.35. Almost half of all knees had change greater than
      smallest detectable difference at 2 years. Body mass index, gender and alignment
      had only a small effect on the rate of change of bone area. CONCLUSIONS: Changes
      in bone area discriminated people with OA from controls and was more responsive
      than the current and impending standards for assessing OA progression. The shape
      change in OA bone provides a new window on OA pathogenesis and a focus for
      clinical trials.

PMID- 24306108
TI  - Notch3 establishes brain vascular integrity by regulating pericyte number.
AB  - Brain pericytes are important regulators of brain vascular integrity,
      permeability and blood flow. Deficiencies of brain pericytes are associated with
      neonatal intracranial hemorrhage in human fetuses, as well as stroke and
      neurodegeneration in adults. Despite the important functions of brain pericytes,
      the mechanisms underlying their development are not well understood and little is
      known about how pericyte density is regulated across the brain. The Notch
      signaling pathway has been implicated in pericyte development, but its exact
      roles remain ill defined. Here, we report an investigation of the Notch3 receptor
      using zebrafish as a model system. We show that zebrafish brain pericytes express
      notch3 and that notch3 mutant zebrafish have a deficit of brain pericytes and
      impaired blood-brain barrier function. Conditional loss- and gain-of-function
      experiments provide evidence that Notch3 signaling positively regulates brain
      pericyte proliferation. These findings establish a new role for Notch signaling
      in brain vascular development whereby Notch3 signaling promotes expansion of the
      brain pericyte population. 

PMID- 24306111
TI  - Health: Mirage and reality.

PMID- 24306110
TI  - Prolonged P-wave duration is associated with atrial fibrillation recurrence after
      successful pulmonary vein isolation for paroxysmal atrial fibrillation.
AB  - Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) is
      successful in ~70-80 % after repeated procedures. This suggests a subgroup of PAF
      patients where electrical abnormalities outside the pulmonary veins are
      important. Prolonged P-wave duration (PWD), a marker of atrial remodelling, may
      identify this subgroup. This study's aim was to assess the association of PWD on
      standard 12 lead ECG with AF recurrence post PVI. METHODS: Retrospectively, ECGs
      were blindly analysed on PVI patients from August 2007-August 2011; patients with
      persistent AF, mitral valve disease, undergoing redo procedures or no sinus
      rhythm (SR) ECG within 1 year of PVI were excluded. ECGs were directly uploaded
      at 300 dpi, amplified *10, and then PWD measured in all leads. Prolonged PWD was
      as priori defined as maximum PWD >= 140 ms. RESULTS: The selective cohort
      consisted of 100 patients out of a total of 170 PVI: age 58 +/- 11 years, 72 %
      male, LVEF 62 +/- 9 %, 18 % ischaemic heart disease and 13 % diabetic. Thirty
      five had prolonged PWD, which was associated with greater AF recurrence rates
      compared to those without prolonged PWD (63 vs. 38 %, p < 0.05). Similarly, AF
      recurrence was associated with greater maximum PWD (139 +/- 17 vs. 129 +/- 14, p
      < 0.01), P-wave dispersion (58 +/- 21 vs. 49 +/- 15, p < 0.01), left atrium (LA)
      dimension (41 +/- 6 vs. 38 +/- 5, p < 0.05) and LA volumes (40 +/- 14 vs. 34 +/-
      11, p < 0.05) compared to those who remained in SR. None of these variables were
      independent predictors of AF recurrence by multivariate analysis. CONCLUSION: The
      presence of pre-existent prolonged PWD is associated with a higher risk of AF
      recurrence post PVI for paroxysmal AF.

PMID- 24306112
TI  - A psychological approach to ethics.
AB  - This article has the purpose of calling attention to C.G. Jung's archetypal
      concept of the Self as an approach to ethics. The distinction between simple
      morality and transcendent ethics is established. Comparison is made between the
      archetype of the Self and Kant's categorical imperative. Freud's superego,
      however, is assimilated to a "natural" outlook on morality, such as the notion of
      altruism in sociobiology. The superego is only the psychic effect of the current
      moral code-which could be explained either culturally or as a Lamarckian acquired
      characteristic of the unconscious. Jung's transcendent ethics is expressed in an
      "ethical mandala." 

PMID- 24306113
TI  - Religion and youth substance use.
AB  - This research study of 13,878 youths indicates that religion is not by itself a
      very important predictor of youth substance use. It is, however, more strongly
      related to alcohol use than drug use. Also, fundamentalist religious groups have
      the lowest percentages of substance use in general, while the more liberal types
      of religious groups have the lowest percentages of heavy substance use. Of the
      six dimensions of religion used in the study to predict youth substance use,
      importance of religion to the subject was the most important, with church
      membership second, and the fundamentalism-liberalism scale of religious groups
      third. 

PMID- 24306114
TI  - Anxiety, as experienced by chronic pain patients.
AB  - This article developed out of the author's work with patients at the Pain Control
      Center at Emory University Hospital in Atlanta, Georgia. The purpose of the
      article is to show how anxiety, an experience common to all persons, is
      particularly experienced by chronic pain patients. 

PMID- 24306115
TI  - A journey in pastoral care: A case study.
AB  - What is pastoral care? Many health professionals are not clear about the role of
      the chaplain on the health care team. This article addresses the question by
      using an actual case study to demonstrate how the chaplain interacts with the
      patient and the value of this interaction to the well-being of the patient. It
      attempts to define, by example, pastoral care. 

PMID- 24306116
TI  - Family tensions and Halakhic guidelines: An intergenerational view.
AB  - Jewish Orthodox families, like all families, face problems in their daily lives.
      Their family tensions and conflicts, however, can be mitigated by presenting
      Halakhic guidelines within an intergenerational context. This article presents
      such an approach, focusing on both intergenerational and Halakhic frameworks for
      facilitating family functioning. 

PMID- 24306117
TI  - Death: Bridge between science and spirit.
AB  - It is argued that contemporary health science, being part of a general cultural
      trend toward the materialism of scientific rationality, has reduced human health
      to a system of machine-like events. This philosophical trend has had the indirect
      effect of excluding the human spirit from playing any significant role in our
      understanding of man's health and well-being. The recent effort of biomedical
      science to extend this materialist philosophy into the area of human death and
      dying is examined in the context of this ideological trend. It is suggested that
      the trend has brought about an ever-widening conceptual gap between the realms of
      spirit and matter. The issue of bridging this contemporary conceptual gap is
      discussed in terms of recent research findings that suggest that the human brain
      may be capable of intergrating the logic of two seemingly irreconcilable ways of
      thinking into a whole which is enriched from the presence of both. This holistic
      possibility is discussed in the context of the philosophies that support the
      existence of spirit and matter. 

PMID- 24306118
TI  - Erratum.

PMID- 24306119
TI  - Role of sunitinib and SU12662 on dermatological toxicities in metastatic renal
      cell carcinoma patients: in vitro, in vivo, and outcomes investigation.
AB  - PURPOSE: Sunitinib commonly exhibits dose-limiting dermatological toxicities
      (DTs) that adversely affect health-related quality of life (HRQoL).
      Pharmacological activity of sunitinib is attributed to sunitinib and an
      equipotent, active metabolite, SU12662. The objective of this study is to compare
      the dermatotoxic potential of sunitinib and SU12662, and changes in HRQoL due to
      DTs. METHODS: A prospective cohort study was conducted on metastatic renal cell
      carcinoma patients. Plasma drug concentrations were determined by high
      performance liquid chromatography. DTs were graded by Common Terminology Criteria
      for Adverse Events. HRQoL of patients with hand-foot skin reaction (HFSR) was
      assessed by the hand-foot syndrome-specific quality-of-life questionnaire (HFS
      14). In addition, the IC50s of both compounds were determined with HaCaT
      keratinocytes. RESULTS: Sunitinib was more dermatotoxic in vitro, with a lower
      IC50 than SU12662 (23.33 vs. 35.32 MUM, p = 0.02). Similar results were observed
      in vivo, with higher sunitinib-to-SU12662 ratio in patients with pruritus, than
      patients without pruritus (p = 0.04). Higher HFS-14 scores were observed in
      patients with higher HFSR grade and in those with both hands and feet affected,
      indicating poorer HRQoL. CONCLUSIONS: Sunitinib may be more dermatotoxic than
      SU12662 from both in vivo and in vitro evidences. Therefore, appropriate
      management of DTs may be essential, especially in patients with a reduced
      sunitinib metabolising ability.

PMID- 24306120
TI  - Autophagy, a novel target for chemotherapeutic intervention of thyroid cancer.
AB  - PURPOSE: Thyroid cancers with unsatisfactory curative effect nowadays are the
      most common malignant tumors of the endocrine system. Apoptosis evasion, a
      hallmark of cancer, has driven the search of stimulating novel cell death way in
      cancer therapy. This review aims to explore the relationship between autophagy
      and thyroid cancer, especially the chemotherapy agents which are based on
      autophagy in treating thyroid cancers. METHODS: A computerized literature search
      of MEDLINE was performed using the following search terms: autophagy and thyroid
      cancer. RESULTS: Recent studies have found that several chemotherapeutic agents
      and knockdown of specific microRNA may contribute to autophagic tumor cell death
      in most thyroid cancer types. CONCLUSIONS: Stimulating autophagy may be an
      effective alternative treatment to most types of thyroid cancer.

PMID- 24306121
TI  - Rapid collapse of the humeral head after arthroscopic rotator cuff repair.
AB  - This report presents a case of rapidly progressive collapse of the humeral head
      following arthroscopic rotator cuff repair. We performed humeral head replacement
      8 months after the index surgery; histological examination of the collapsed area
      revealed necrosis, degeneration, fibrillation, and granulation in the cartilage
      and trabeculae. Osteonecrosis due to the use of metal anchors was considered the
      primary cause of the post-operative humeral head collapse. As the demand for
      arthroscopic cuff repair is expected to increase in the future, we recommend that
      surgeons become aware of the potential for complications, as seen in the present
      case. LEVEL OF EVIDENCE: IV.

PMID- 24306122
TI  - High accuracy in knee alignment and implant placement in unicompartmental medial
      knee replacement when using patient-specific instrumentation.
AB  - PURPOSE: The influence of patient-specific instrumentations on the accuracy of
      unicompartmental medial knee replacement remains unclear. The goal of this study
      was to examine the ability of patient-specific instrumentation to accurately
      reproduce postoperatively what the surgeon had planned preoperatively. METHODS:
      Twenty consecutive patients (20 knees) who suffered from isolated
      unicompartmental medial osteoarthritis of the knee and underwent medial knee
      replacement using newly introduced magnetic resonance imaging-based patient
      specific instrumentation were assessed. This assessment recorded the following
      parameters: (1) the planned and the postoperative mechanical axis acquired
      through long-leg AP view radiographies; (2) the planned and the postoperative
      tibial slope acquired by means of standard AP and lateral view radiographies; and
      (3) the postoperative fit of the implanted components to the bone in coronal and
      sagittal planes. The hypothesis of the study was that there was no statistically
      significant difference between postoperative results and preoperatively planned
      values. RESULTS: The study showed that (1) the difference between the
      postoperative mechanical axis (mean 1.9 degrees  varus +/- 1.2 degrees  SD) and
      the planned mechanical axis (mean 1.8 degrees  varus +/- 1.2 degrees  SD) was not
      statistically significant; (2) the difference between the postoperative tibial
      slope (mean 5.2 degrees  +/- 0.6 degrees  SD) and the planned tibial slope (mean
      5.4 degrees  +/- 0.6 degrees  SD) was statistically significant (p = 0.008); and
      (3) the postoperative component fit to bone in the coronal and sagittal planes
      was accurate in all cases; nevertheless, in one knee, all components were
      implanted one size smaller than preoperatively planned. Moreover, in two
      additional cases, one size thinner and one size thicker of the polyethylene
      insert were used. CONCLUSIONS: This study suggests that overall patient-specific
      instrumentation was highly accurate in reproducing postoperatively what the
      surgeon had planned preoperatively in terms of mechanical axis, tibial slope and
      component fit to bone. LEVEL OF EVIDENCE: IV.

PMID- 24306123
TI  - Current state of treatment of acute acromioclavicular joint injuries in Germany:
      is there a difference between specialists and non-specialists? A survey of German
      trauma and orthopaedic departments.
AB  - PURPOSE: The purpose of this study was to evaluate currently preferred treatment
      strategies as well as the acceptance of new arthroscopic techniques among German
      orthopaedic surgeons. We assumed that surgeons specialized in shoulder surgery
      and arthroscopy would treat acute acromioclavicular joint dislocations different
      to non-specialized surgeons. METHODS: Seven hundred and ninety-six orthopaedic
      and/or trauma departments were found through the German hospital directory of
      2012. Corresponding websites were searched for the email address of the chair of
      shoulder surgery (if applicable) or the department. Seven hundred forty-six
      emails with the request for study participation including a link to an online
      survey of 36 questions were sent. In 60 emails, the recipient was unknown.
      RESULTS: Two hundred and three (30 %) surgeons participated in the survey. one
      hundred and one were members of the AGA (German-speaking Society for Arthroscopy
      and Joint-Surgery) and/or of the DVSE (German Association of Shoulder and Elbow
      Surgery) and regarded as specialists, while 102 were non-members and regarded as
      non-specialists. According to the treatment of Rockwood I/II and IV-VI injuries,
      no significant differences were found. Seventy-four % of non-specialists and 67 %
      of specialists preferred surgical treatment for Rockwood III injuries (P =
      0.046). Non-specialists would use the hook plate in 56 % followed by the
      TightRope in 16 %; specialists would use the TightRope in 38 % followed by the
      hook plate in 32 % (P = 0.004). CONCLUSIONS: The majority of German orthopaedic
      and trauma surgeons advise surgical treatment for Rockwood III injuries.
      Specialists recommend surgery less often. Non-specialists prefer the hook plate,
      whereas specialists prefer the arthroscopic TightRope technique. LEVEL OF
      EVIDENCE: Observational survey, Level IV.

PMID- 24306125
TI  - Multi-nuclear silver(I) and copper(I) complexes: a novel bonding mode for
      bispyridylpyrrolides.
AB  - Reaction of deprotonated 2,5-bis(2'-pyridyl)pyrrole (HPDPH) with AgOTf (where
      OTf(-) = triflato) in THF readily yields a yellow triangular Ag3 complex
      [(PDPH)Ag]3 (1), of which the av. AgAg distance is 2.902 A. A mixture of HPDPH
      and AgOTf reacts with PPh3 to afford a linear Ag3 complex
      [Ag{(PDPH)Ag(PPh3)}2](OTf) (2.OTf), whereas it reacts with diethyl phosphite in
      the presence of Li[N(SiMe3)2] to yield a di-nuclear complex
      Li2[(PDPH)Ag2{P(O)(OEt)2}2](OTf) (Li2.3.OTf). In 2, the terminal Ag atoms are
      three coordinate containing one phosphorous atom from PPh3 and two nitrogen atoms
      of the PDPH ligand. The center Ag atom is only two coordinate, binding to the
      residued pyridyl N atom of the PDPH ligand. In 3, two silver atoms are bridged by
      one PDPH ligand. Treatment of PDPH with CuCl in the presence of NaH afforded a
      heterobimetallic copper-sodium complex [Cu(PDPH)2Na(thf)2] (4). The PDPH ligand
      in 1-4 is nonplanar, with torsion angles between pyridine and pyrrole rings in
      the range of 15.8-38.3 degrees . The argentophilic interactions, pi???pi
      stacking, and weak interaction of Ag???C(aromatic) are observed in these
      complexes. Interestingly, treatment of the analogous 2,5-bis(6'-bromo-2'
      pyridyl)pyrrole (HPDPBr) with AgOTf affords a di-nuclear complex
      [(HPDPBr)Ag]2(OTf)2 (5.(OTf)2). Its HPDPBr ligands coordinate to Ag atoms in a
      head-to-head fashion, and two protonated pyrrole linkages reside in the anti
      parallel direction and are non-coordinating. Short AgBr distances of 3.255-3.390
      A are observed.

PMID- 24306124
TI  - Arthroscopic reduction and internal fixation of acetabular fractures.
AB  - Arthroscopic reduction and screw fixation of acetabular fractures have not been
      reported. In this case report, arthroscopic treatment for acetabular fracture is
      reported for two patients. A 49-year-old man diagnosed with acetabular posterior
      wall fracture was treated by arthroscopic reduction and fixation using two
      screws. A 20-year-old woman who diagnosed with anterior column fracture was fixed
      using a screw using the arthroscopic technique prior to open reduction and
      internal fixation in the iliac bone fracture. Arthroscopic reduction and fixation
      in some case of acetabular fracture could be good indication with additional
      advantages of joint debridement and loose body removal.

PMID- 24306126
TI  - Symposium: Futures in Reproduction.

PMID- 24306127
TI  - Diffuse ulcerated skin rash.

PMID- 24306128
TI  - Introduction of ERAS((r)) program into clinical practice: from preoperative
      management to postoperative evaluation : Opening remarks.

PMID- 24306129
TI  - The lowest effective intracuff pressure of the esophagus obstruction tube to
      prevent reflux of gastric contents: a study on rabbits.
AB  - PURPOSE: To determine the lowest effective cuff pressure of the esophageal
      obstruction tube to prevent reflux of gastric contents in rabbits. METHODS:
      Twenty-two New Zealand white rabbits (2.0-2.5 kg) were anesthetized. An
      esophageal obstruction tube, an esophageal observation tube, and a gastric tube
      were inserted into the esophagus and stomach, respectively. Normal saline
      containing methylene blue was injected into the stomach for an animal model of
      gastric contents reflux. Possible saline reflux was observed through the
      esophageal observation tube. It was considered "regurgitation" when the saline
      flowed out, and "no regurgitation" when the saline did not. When a
      "regurgitation" result was obtained in a particular rabbit, the intracuff
      pressure was increased by 10 cm H(2)O in the following rabbit and vice versa. The
      trial was not terminated until six crossover points were observed from "no
      regurgitation" to "regurgitation." A probit regression model was used to analyze
      the effective intracuff pressure of the esophagus obstruction tube after 50 % and
      95 % of the rabbits showed no reflux. RESULTS: The lowest effective intracuff
      pressure to prevent reflux of gastric contents in 50 % of rabbits from the Dixon
      up-down method was 61.67 +/- 8.16 cm H(2)O. The intracuff pressures at which
      there was 50 % and 95 % probability of lack of gastric contents reflux from a
      probit regression model were 61.95 and 74.39 cm H(2)O, respectively. CONCLUSION:
      The insertion of an esophageal obstruction tube before endotracheal intubation
      can be an acceptable method for preventing the reflux of gastric contents in most
      rabbits under light anesthesia.

PMID- 24306131
TI  - Reaching out to take on TB in Somalia.
AB  - Among the many challenges facing populations disrupted by complex emergencies,
      personal security and food security rank much higher than access to healthcare.
      However, over time health needs assume increasing importance. Many complex crises
      occur in settings where the background incidence of TB is already high; social
      and economic conditions in crises are then highly conducive to amplification of
      the existing TB problem. Innovative approaches to delivery of diagnostic and
      treatment services, transition planning and integration with other healthcare
      providers and services are vital. In the extremely challenging environment of
      Somalia, multiple partners are making headway though collaboration and
      innovation.

PMID- 24306130
TI  - Analysis of quinolone-resistance in commensal and diarrheagenic Escherichia coli
      isolates from infants in Lima, Peru.
AB  - BACKGROUND: Antibiotic resistance is an increasing problem, particularly in
      countries where antibiotic use is frequently not controlled. The aim of this
      study was to analyse the prevalence of the molecular mechanisms of quinolone
      resistance in E. coli isolated from faeces of healthy Peruvian children or those
      presenting diarrhoea. METHODS: The presence of target mutations, transferable
      quinolone-resistance mechanisms and the role of Phe-Arg-beta-Naphtylamyde
      inhibitible efflux pumps were studied in 96 Escherichia coli (46 diarrheogenic
      and 50 non-diarrheogenic) isolates exhibiting resistance or diminished
      susceptibility to quinolones. RESULTS: The most resistant phenotype, Nal(R) and
      Cip(R), was most frequently present in isolates of healthy children. The
      distribution of quinolone resistance mechanisms between diarrheogenic (DEC) and
      commensal (non DEC) isolates was equitable, although the aac(6')Ib-cr gene was
      mainly detected in DEC isolates: 17 (34%) vs non DEC isolates nine (20%). QnrB
      was present in five (10%) DEC vs three (6%) non DEC isolates. CONCLUSIONS: Point
      mutations in gyrA and parC genes play a relevant role in quinolone resistance
      acquisition and highlight the role of efflux pumps also. This study provides
      knowledge about the molecular mechanisms involved in quinolone resistance in
      isolates in a non exposed population under high community antibiotic pressure.

PMID- 24306132
TI  - Improved effect of the combination naltrexone/D-penicillamine in the prevention
      of alcohol relapse-like drinking in rats.
AB  - Opioid antagonists are licensed drugs for treating alcohol use disorders;
      nonetheless, clinical studies have evidenced their limited effectiveness.
      Preclinical findings indicate that opioid receptor (OR) antagonists, such as
      naltrexone (NTX), reduce the alcohol deprivation effect (ADE). However, a
      detailed analysis of published data shows the existence of a delayed increase in
      ethanol consumption after continuous OR blockade, a phenomenon originally called
      as 'delayed ADE'. We have recently reported that D-penicillamine (DP) is able to
      prevent ADE through a mechanism dependent on the inactivation of acetaldehyde,
      the main metabolite of ethanol. Hypothetically, OR activation would be triggered
      by acetaldehyde after ethanol consumption. Hence, we conjecture that the
      combination of NTX and DP, due to their distinct but complementary mechanisms to
      impede OR activation, may be more efficacious in the prevention of the ADE and,
      specifically, the 'delayed ADE'. Herein, we compare the effects of the
      combination NTX/DP (NTX: 2*5 mg/kg SC injection daily/DP: SC infusion (0.25
      mg/h)) versus NTX on the ADE in long-term ethanol-experienced rats. As expected,
      NTX-treated animals displayed a delayed ADE. However, NTX/DP treatment prevented
      this delayed effect. Our present data indicate that this combination therapy
      shows an adequate anti-relapse preclinical efficacy being able to overcome the
      preclinical limitations of NTX alone. 

PMID- 24306133
TI  - Improvement in daytime sleepiness with clarithromycin in patients with GABA
      related hypersomnia: Clinical experience.
AB  - The macrolide antibiotic clarithromycin can enhance central nervous system
      excitability, possibly by antagonism of GABA-A receptors. Enhancement of GABA
      signaling has recently been demonstrated in a significant proportion of patients
      with central nervous system hypersomnias, so we sought to determine whether
      clarithromycin might provide symptomatic benefit in these patients. We performed
      a retrospective review of all patients treated with clarithromycin for
      hypersomnia, in whom cerebrospinal fluid enhanced GABA-A receptor activity in
      vitro in excess of controls, excluding those with hypocretin deficiency or
      definite cataplexy. Subjective reports of benefit and objective measures of
      psychomotor vigilance were collected to assess clarithromycin's effects. Clinical
      and demographic characteristics were compared in responders and non-responders.
      In total, 53 patients (38 women, mean age 35.2 (SD 12.8 years)) were prescribed
      clarithromycin. Of these, 34 (64%) reported improvement in daytime sleepiness,
      while 10 (19%) did not tolerate its side effects, and nine (17%) found it
      tolerable but without symptomatic benefit. In those who reported subjective
      benefit, objective corroboration of improved vigilance was evident on the
      psychomotor vigilance task. Twenty patients (38%) elected to continue
      clarithromycin therapy. Clarithromycin responders were significantly younger than
      non-responders. Clarithromycin may be useful in the treatment of hypersomnia
      associated with enhancement of GABA-A receptor function. Further evaluation of
      this novel therapy is needed. 

PMID- 24306134
TI  - Alcohol disrupts the effects of priming on the perception of ambiguous figures.
AB  - Inhibitory mechanisms are thought to underpin the well-documented impairing
      effects of alcohol on attention. Here, we use a novel priming paradigm to
      investigate the effects of alcohol on inhibitory mechanisms in attention.
      Participants were assigned to an alcohol (N=15), or placebo (N=15) group. The
      dose of alcohol was 0.8 g/kg for males and 0.75 g/kg for females. Participants
      were asked to report figure reversals during presentation of the face-vase
      ambiguous figure. Prior to this, they were shown a prime that was either
      semantically relevant to the face-vase stimulus or was neutral. Semantic priming
      decreased the number of figure reversals in the first half of the test session in
      the placebo group but not in the alcohol group. The placebo group was also more
      likely than the alcohol group to report the first interpretation of the figure to
      be the same as the semantic prime. Prior presentation of a semantic prime had a
      stabilising effect on reversal rate, suggesting that the primed interpretation
      inhibited the alternate interpretation. The absence of an effect in the alcohol
      group is consistent with an alcohol-related impairment of this inhibition. 

PMID- 24306135
TI  - Duration of activity and mode of action of modafinil: Studies on sleep and
      wakefulness in humans.
AB  - The duration of activity of modafinil was investigated in healthy male volunteers
      in two double-blind crossover studies. Mode of action was explored using a
      statistical model concerned with the relationship between total sleep duration
      and that of rapid eye movement (REM) sleep. Nocturnal sleep (23:00-07:00)
      followed by next-day performance (09:00-17:00) was studied in 12 subjects
      administered 100, 200, 300 mg modafinil and placebo, 0.5 h before bedtime.
      Performance overnight (19:00-08:45) followed by sleep (09:15-15:15) was studied
      in nine subjects administered 100, 200, 300, 400 mg modafinil, 300 mg caffeine
      and placebo at 22:15. Modafinil dose-dependently reduced sleep duration
      (nocturnal: 200 mg, p<0.05; 300 mg, p<0.001; morning: 300 and 400 mg, p<0.05) and
      REM sleep (nocturnal: 300 mg; morning: 400 mg; p<0.05). The statistical model
      revealed that reduced REM sleep was due to alerting activity, with no evidence of
      direct suppression of REM sleep, suggesting dopaminergic activity. Enhanced
      performance with modafinil during overnight work varied with dose (200 mg>100 mg;
      300, 400 mg>200, 100 mg, caffeine). However, in the study of next-day
      performance, the enhancement was attenuated at the highest dose (300 mg) by the
      greater disturbance of prior sleep. These findings indicate that modafinil has a
      long duration of action, with alerting properties arising predominantly from
      dopaminergic activity. 

PMID- 24306136
TI  - Brain metastases from breast cancer: lessons from experimental magnetic resonance
      imaging studies and clinical implications.
AB  - Breast cancer that has metastasized to the brain presents difficult clinical
      challenges. This diagnosis comes with high mortality rates, largely due to
      complexities in early detection and ineffective therapies associated with both
      dormancy and impermeability of the blood-brain barrier (BBB). Magnetic resonance
      imaging (MRI) is the current gold standard for diagnosis and assessment of brain
      tumors. It has been used clinically to investigate metastatic development as well
      as monitor response to therapy. Here, we describe preclinical imaging strategies
      that we have used to study the development of brain metastases due to breast
      cancer. Using this approach, we have identified three subsets of metastatic
      disease: permeable metastases, nonpermeable metastases, and solitary, dormant
      cancer cells, which likely have very different biology and responses to therapy.
      The ability to simultaneously monitor the spatial and temporal distribution of
      dormant cancer cells, metastatic growth, and associated tumor permeability can
      provide great insight into factors that contribute to malignant proliferation.
      Our preclinical findings suggest that standard clinical detection strategies may
      underestimate the true metastatic burden of breast cancer that has metastasized
      to the brain. A better understanding of true metastatic burden in brains will be
      important to assist in the development of more effective chemotherapeutics
      particularly those targeted to cross the BBB-as well as detection of small
      nonpermeable metastases. 

PMID- 24306137
TI  - Children with asthma versus healthy children: differences in secondhand smoke
      exposure and caregiver perceived risk.
AB  - INTRODUCTION: Secondhand smoke (SHS) exposure remains a public health problem.
      Few, if any, studies include both children with and without asthma to assess
      differences in caregiver smoking behavior, risk perception, and SHS. METHODS:
      Participants were 738 daily U.S. smokers (443 caregivers of children with asthma
      [CG-AC] and 295 caregivers of healthy children [CG-HC]; 50.9% White, 25% Black,
      15% Latino). Data are cross-sectional; SHS was measured through self-report and
      passive dosimetry. RESULTS: Compared with CG-HC, CG-AC had fewer risk factors for
      exposing children to SHS (lower nicotine dependence, higher motivation to quit,
      greater perceived benefits of cessation on child's health, and lower optimistic
      bias; all p values < .05). Specifically, 60.6% of CG-AC reported a household
      smoking ban versus 40.1% of CG-HC (p < .05), though >95% of both groups had
      detectable levels of SHS in their home. CG-AC self-reported lower SHS than CG-HC,
      but both groups had nearly equivalent SHS when measured objectively. CG-AC were
      almost twice as likely as CG-HC to report a home smoking ban when they had
      detectable levels of household SHS as measured by passive dosimetry (OR = 1.71;
      95% CI = 1.2, 2.4; p = .003). CONCLUSIONS: Caregivers of children with chronic
      health conditions, such as asthma, may be motivated to self-report lower levels
      of SHS. Child health status (e.g., asthma) may cue practitioners to inquire about
      SHS, but given the low proportion of household bans and high levels of actual
      exposure among both groups, SHS exposure assessment and reduction/elimination
      counseling should be prompted to occur for all children.

PMID- 24306138
TI  - An R2R3-MYB transcription factor as a negative regulator of the flavonoid
      biosynthesis pathway in Ginkgo biloba.
AB  - Flavonoids are secondary metabolites that contribute substantially to the quality
      of Ginkgo biloba. Plant flavonoid accumulation is controlled by transcriptional
      regulation of the genes that encode the biosynthetic enzymes, in which the R2R3
      MYB transcription factor is a key factor. In this study, we describe the cloning
      and functional characterization of a R2R3-MYB transcription factor gene, GbMYBF2,
      isolated from G. biloba. GbMYBF2 encodes a protein belonging to a small subfamily
      of R2R3-MYB transcription factors. Comparative and bioinformatics analyses showed
      that GbMYBF2 is more closely related to the repressor R2R3-MYB subfamily involved
      in flavonoid biosynthesis. Tissue expression pattern analysis showed that GbMYBF2
      was constitutively expressed in leaves, fruits, stems, and roots, wherein the
      level of transcription in the roots is significantly higher than that in the
      stems, leaves, and fruits. During G. biloba leaf growth, the transcription of
      GbMYBF2 is negatively correlated with the flavonoid content, suggesting that the
      GbMYBF2 gene is responsible for the repressed flavonoid biosynthesis. Transgenic
      Arabidopsis plants that overexpress GbMYBF2 exhibit an inhibition of flavonoid
      and anthocyanin biosynthesis compared with the untransformed Arabidopsis plants.
      In addition, the overexpression of GbMYBF2 in Arabidopsis clearly downregulates
      the expression of the structural genes that control the synthesis of flavonoids
      and anthocyanins. These findings suggest that GbMYBF2 may have a key role in
      repressing transcription in regulating the biosynthesis of flavonoids in G.
      biloba. 

PMID- 24306139
TI  - Prolonged duration of type 2 diabetes is associated with increased thrombin
      generation, prothrombotic fibrin clot phenotype and impaired fibrinolysis.
AB  - It has been shown that type 2 diabetes (DM) is associated with enhanced thrombin
      generation and formation of denser fibrin clots of reduced lysability. We sought
      to investigate the impact of diabetes duration versus glycaemia control on fibrin
      clot phenotype and its determinants in type 2 diabetic patients. In 156
      consecutive Caucasian patients with type 2 diabetes we investigated ex vivo
      thrombin generation, fibrinolytic proteins, along with plasma fibrin clot
      permeation (Ks), compaction, turbidity, and efficiency of tissue plasminogen
      activator (t-PA)-mediated fibrinolysis. Patients with longer diabetes duration
      (>5 years, median; n=68) had higher peak thrombin generation (+16.3%, p<0.001),
      plasminogen activator inhibitor-1 (PAI-1) antigen (+14.8%, p=0.001), t-PA antigen
      (+13.9%, p=0.002) compared with those with duration <=5 years (n=88). No such
      differences were observed between patients with inadequate glycaemic control,
      defined as glycated haemoglobin (HbA1C) >6.5% (48 mmol/mol) (n=77), versus those
      with HbA1C<=6.5% (n=79). Fibrinogen, thrombin-activatable fibrinolysis inhibitor
      antigen, plasminogen and soluble thrombomodulin were unaffected by disease
      duration or glycaemia control. Lower clot permeability, longer clot lysis, and
      higher maximum D-dimer levels released from clots (all p<0.05 after adjustment
      for fibrinogen, age, body mass index, insulin, acetylsalicylic acid treatment,
      and HbA1c or diabetes duration) were also observed in patients with diabetes
      duration >5 years and those with HbA1C>6.5%. We conclude that prolonged duration
      of type 2 diabetes is associated with increased thrombin formation,
      hypofibrinolysis, and prothrombotic fibrin clot phenotype. The impact of disease
      duration on coagulation is different and stronger than that observed during
      inadequate glycaemia control. 

PMID- 24306140
TI  - Factors which impact the delivery of genetic risk assessment services focused on
      inherited cancer genomics: expanding the role and reach of certified genetics
      professionals.
AB  - There is tremendous excitement about the promise of new genomic technologies to
      transform medical practice and improve patient care. Although the full power of
      genetic diagnosis has not yet been realized, paradigms of clinical decision
      making are changing. In fact, recent policy level changes to promote genetic
      counseling by certified genetics professionals (GP) such as genetic counselors
      and clinical geneticists, are occurring at both the payer and state level.
      However, there remain opportunities to develop policies within the United States
      to: 1) enhance the access to the limited workforce of GPs; 2) revise
      reimbursement schemes such that costs to deliver these services may be recouped
      by institutions with GPs; and 3) protect against the potential for discrimination
      based on genetic information. Although many of these issues predate advances in
      genomic technologies, they are exacerbated by them, with increasing access and
      awareness as costs of testing decrease. Consequently, evolving shifts in national
      policies poise GPs to serve as a hub of information and may be instrumental in
      facilitating new models to deliver genetics-based care through promoting academic
      community partnerships and interfacing with non-GPs. As we acknowledge the
      potential for genomics to revolutionize medical practice, the expertise of GPs
      may be leveraged to facilitate incorporation of this information into mainstream
      medicine. 

PMID- 24306141
TI  - Diagnostic exome sequencing identifies two novel IQSEC2 mutations associated with
      X-linked intellectual disability with seizures: implications for genetic
      counseling and clinical diagnosis.
AB  - Intellectual disability is a heterogeneous disorder with a wide phenotypic
      spectrum. Over 1,700 OMIM genes have been associated with this condition, many of
      which reside on the X-chromosome. The IQSEC2 gene is located on chromosome
      Xp11.22 and is known to play a significant role in the maintenance and
      homeostasis of the brain. Mutations in IQSEC2 have been historically associated
      with nonsyndromic X-linked intellectual disability. Case reports of affected
      probands show phenotypic overlap with conditions associated with pathogenic
      MECP2, FOXG1, CDKL5, and MEF2C gene mutations. Affected individuals, however,
      have also been identified as presenting with additional clinical features
      including seizures, autistic-behavior, psychiatric problems, and delayed language
      skills. To our knowledge, only 5 deleterious mutations and 2 intragenic
      duplications have been previously reported in IQSEC2. Here we report two novel
      IQSEC2 de novo truncating mutations identified through diagnostic exome
      sequencing in two severely affected unrelated male probands manifesting
      developmental delay, seizures, hypotonia, plagiocephaly, and abnormal MRI
      findings. Overall, diagnostic exome sequencing established a molecular diagnosis
      for two patients in whom traditional testing methods were uninformative while
      expanding on the mutational and phenotypic spectrum. In addition, our data
      suggests that IQSEC2 may be more common than previously appreciated, accounting
      for approximately 9 % (2/22) of positive findings among patients with seizures
      referred for diagnostic exome sequencing. Further, these data supports recently
      published data suggesting that IQSEC2 plays a more significant role in the
      development of X-linked intellectual disability with seizures than previously
      anticipated. 

PMID- 24306142
TI  - Informing children of their newborn screening carrier result for sickle cell or
      cystic fibrosis: qualitative study of parents' intentions, views and support
      needs.
AB  - Newborn screening for cystic fibrosis and sickle cell disease enables the early
      identification and treatment of affected children, prolonging and enhancing their
      quality of life. Screening, however, also identifies carriers. There are minimal
      or no health concerns for carriers. There are, however, potential implications
      when carriers reach reproductive age, and thus research attention has been given
      to how best to convey information about these implications in a meaningful,
      balanced way which does not raise undue anxieties. Most research focuses on the
      communication from health professional to parent, yet ultimately this information
      is of greatest significance to the child. This study examines parents' intentions
      to inform their child of newborn screening carrier results. Semi-structured
      interviews with 67 family members explored their intentions to inform the child,
      and related views and support needs. Parents almost unanimously indicated they
      planned to inform the child themselves. Health professionals were expected,
      however, to provide guidance on this process either to parents through advice and
      provision of written materials, or directly to the child. Although parents
      initially stated that they would convey the result once their child had developed
      the ability to understand the information, many appeared to focus on discrete
      life events linked to informed reproductive decision making. The results
      highlight ways in which health care providers may assist parents, including
      providing written material suitable for intergenerational communication and
      ensuring that cascade screening is accessible for those seeking it. Priorities
      for further research are identified in light of the results. 

PMID- 24306143
TI  - CuI-catalyzed cycloisomerization of propargyl amides.
AB  - The synthesis of substituted dihydrooxazoles by the CuI-catalyzed
      cycloisomerization of terminal propargyl amides is reported. The reaction has
      been shown to have good substrate scope and experiments to delineate the
      mechanism have been performed. Substrates containing a benzylic methylene were
      oxidized to the ketone under the reaction conditions. 

PMID- 24306144
TI  - Perceived maternal and paternal psychological control: relations to adolescent
      anxiety through deficits in emotion regulation.
AB  - The current study compared the differential effects of early adolescents'
      perceived maternal and paternal psychological control (as well as their
      discrepancy) on adolescent anxiety. It also tested whether psychological control
      leads to deficits in youths' ability to regulate their negative emotions, and if,
      in turn, such deficits lead to anxiety. Sixth- and seventh-grade students (n =
      214; 59% girls; 60% Caucasian) completed measures of perceived psychological
      control, regulation of negative emotions, and anxiety symptoms. The discrepancy
      between perceived mothers' and fathers' control was also calculated. Although
      perceptions of mothers' control, fathers' control, and their discrepancy were
      each bivariately related to adolescent anxiety, when considered together, only a
      larger discrepancy in parents' psychological control was uniquely associated with
      higher self-reported anxiety. Further, adolescents' dysregulation of negative
      emotions partially explained the relation of both maternal psychological control
      and the discrepancy in parental control to anxiety. Implications for
      understanding family-based etiological correlates of anxiety are discussed.

PMID- 24306145
TI  - Stereolithography in tissue engineering.
AB  - Several recent research efforts have focused on use of computer-aided additive
      fabrication technologies, commonly referred to as additive manufacturing, rapid
      prototyping, solid freeform fabrication, or three-dimensional printing
      technologies, to create structures for tissue engineering. For example, scaffolds
      for tissue engineering may be processed using rapid prototyping technologies,
      which serve as matrices for cell ingrowth, vascularization, as well as transport
      of nutrients and waste. Stereolithography is a photopolymerization-based rapid
      prototyping technology that involves computer-driven and spatially controlled
      irradiation of liquid resin. This technology enables structures with precise
      microscale features to be prepared directly from a computer model. In this
      review, use of stereolithography for processing trimethylene carbonate,
      polycaprolactone, and poly(D,L-lactide) poly(propylene fumarate)-based materials
      is considered. In addition, incorporation of bioceramic fillers for fabrication
      of bioceramic scaffolds is reviewed. Use of stereolithography for processing of
      patient-specific implantable scaffolds is also discussed. In addition, use of
      photopolymerization-based rapid prototyping technology, known as two-photon
      polymerization, for production of tissue engineering scaffolds with smaller
      features than conventional stereolithography technology is considered. 

PMID- 24306147
TI  - A novel nonanuclear hafnium oxide-hydroxide-sulphate cluster crystallised from
      aqueous solution.
AB  - Single crystals of (NH4)14[Hf9O8(OH)6(SO4)14].nH2O (1) were obtained by heating a
      sealed aqueous solution of HfOCl2.8H2O, (NH4)2SO4 and H2SO4 at 80  degrees C for
      10 days. The discrete [Hf9O8(OH)6(SO4)14](14-) anionic clusters have no inter
      cluster connectivity. This rare nonameric architecture has only been observed
      previously in two Bi(3+) oxo clusters.

PMID- 24306146
TI  - Of mice and (wo)men: factors influencing successful implantation including
      endocannabinoids.
AB  - BACKGROUND One in six couples suffer from infertility problems requiring in vitro
      fertilization therapy; however, the average birth rates in the past decade per
      IVF-embryo transfer cycle have remained static at around 25%. Although
      implantation failure is considered a major cause of infertility in otherwise
      healthy women, inadequate uterine receptivity is considered to be responsible for
      only two-thirds of implantation failures and problems with the embryo itself are
      responsible for the other third, such that only 30% of oocytes that are contacted
      by sperm result in successful human term pregnancies. Due to technical and
      ethical considerations, most research into the factors affecting the success of
      embryo implantation has been performed in mice, but this may be less than ideal.
      METHODS Selected relevant literature detailing the similarities and differences
      between rodent and human reproductive physiology surrounding implantation were
      nominated for inclusion. Primary papers and review articles (and primary sources
      within these), published between 1975 and 2012, with a clear indication for a
      particular ligand or cell being involved in the implantation process or
      placentation in the mouse or woman, were thoroughly examined and used to
      construct the review. RESULTS Mice have been identified as suitable models for
      investigating the processes of early pregnancy in women, for many reasons
      including their predictable, relatively short gestation and the ability to
      deliberately breed mice with the absence of a desired gene. There is, however,
      increasing evidence to suggest that the reproductive systems of humans and mice
      differ considerably when considering early pregnancy events. CONCLUSIONS In this
      review, we examine what is already known about the normal implantation process
      and the intrinsic factors that affect implantation, and then compare the
      differences between mice models and women in the context of early pregnancy. We
      highlight numerous differences between the mice and women and conclude it is
      becoming clear that all of the data from mouse studies cannot be confidently
      extrapolated to human reproduction. 

PMID- 24306148
TI  - Comparative studies of tri- and hexavalent chromium cytotoxicity and their
      effects on oxidative state of Saccharomyces cerevisiae cells.
AB  - Chromium is a significant mutagen and carcinogen in environment. We compared the
      effects of tri- and hexavalent chromium on cytotoxicity and oxidative stress in
      yeast. Cell growth was inhibited by Cr(3+) or Cr(6+), and Cr(6+) significantly
      increased the lethal rate compared with Cr(3+). Both Cr(3+) and Cr(6+) can enter
      into the yeast cells. The percent of propidium iodide permeable cells treated
      with Cr(3+) is almost five times as that treated with the same concentration of
      Cr(6+). Levels of TBARS, O2 (-), and carbonyl protein were significantly
      increased in both Cr(6+)- and Cr(3+)-treated cells in a concentration- and time
      dependent manner. Moreover, the accumulation of these stress markers in Cr(6+)
      treated cells was over the Cr(3+)-treated ones. The decreased GSH level and
      increased activity of GPx were observed after 300 MUM Cr(6+)-exposure compared
      with the untreated control, whereas there was no other change of GSH content in
      cells treated with Cr(3+) even at very high concentration. Exposure to both
      Cr(3+) and Cr(6+) resulted in the decrease of activities of SOD and catalase.
      Furthermore, the effect of Cr(6+) is stronger than that of Cr(3+). Null mutation
      sensitivity assay demonstrated that the gsh1 mutant was sensitive to Cr(6+) other
      than Cr(3+), the apn1 mutant is more sensitive to Cr(6+) than Cr(3+), and the
      rad1 mutant is sensitive to both Cr(6+) and Cr(3+). Therefore, Cr(3+) can be
      concluded to inhibit cell growth probably due to the damage of plasma membrane
      integrality in yeast. Although both tri- and hexavalent chromium can induce
      cytotoxicity and oxidative stress, the action mode of Cr(3+) is different from
      that of Cr(6+), and serious membrane damage caused by Cr(3+) is not the direct
      consequence of the increase of lipid peroxidation. 

PMID- 24306149
TI  - Screening for MCL-PHA-producing fluorescent pseudomonads and comparison of MCL
      PHA production under iso-osmotic conditions induced by PEG and NaCl.
AB  - The medium chain length polyhydroxyalkanoates (MCL-PHA) have attracted much
      attention from academic and industrial communities for their interesting
      applications in medical field. The aim of this study was to screen high MCL-PHA
      producing fluorescent pseudomonads, and to compare the effect of osmotic stress
      generated by NaCl (ionic) and polyethylene glycol (PEG, non-ionic inert polymer)
      on PHA production. A total of 50 fluorescent pseudomonads isolated from
      rhizospheric soil were screened for PHA production by Sudan Black staining. Out
      of all the PHA-producing isolates only five were MCL-PHA producers as detected by
      MCL-PCR. Isolate Bar1 identified as Pseudomonas fluorescens by 16S rRNA gene
      sequencing was selected for further analysis due to its high MCL-PHA production
      ability. The iso-osmotic stress generated by NaCl and PEG-6000 showed 5.75- and
      3.19-fold enhanced production of PHA at -2 bar osmotic potential, over control (0
      bar), respectively. There was 1.8-fold enhanced production of PHA at -2 bar
      osmotic stress induced by NaCl over PEG. PEG reduces availability of water to
      microorganisms without reducing exogenously provided nutrients which appear to be
      responsible for its down performance over NaCl. The FTIR analysis of PHA sample
      purified from cells showed strong marker bands near 1742, 2870, 1170, 1099, and
      2926 cm(-1), corresponding to MCL-PHA. The study reported that supplementation of
      NaCl (electrolyte) in growth media enhances the production of MCL-PHA which can
      be very useful for its industrial production. 

PMID- 24306150
TI  - Surface display of human growth hormone on Bacillus subtilis spores for oral
      administration.
AB  - Human growth hormone (hGH) is the major and important hormone component of human
      being. At present, hGH for clinical uses is mostly produced in Escherichia coli,
      which requires costly denaturation and refolding to recover functionality. To
      obtain long-term bioactive hormone, we used hGH as a foreign gene and constructed
      a recombinant plasmid pJS700-hGH which carries a recombinant gene cotC-hgh with
      an enterokinase site under the control of cotC promoter. Plasmid pJS700-hGH was
      transformed into Bacillus subtilis by double crossover and an amylase-inactivated
      mutant was produced. After spore formation, Western blot and fluorescence
      immunoassay were used to monitor hGH surface expression on spores. Oral
      administration to silkworm with spores displaying hGH further showed that the
      recombinant spores may have potential ability to be digested and absorbed into
      the silkworm's hemolymph due to both the resistant characters of spores and the
      addition of enterokinase site. 

PMID- 24306151
TI  - Metabolic features of rats resistant to a high-fat diet.
AB  - OBJECTIVE: We assessed the metabolic characteristics of high-fat-diet-resistant
      (DR) rats. METHODS: Body weight, energy intake, locomotor activity, oxygen
      consumption, plasma leptin and lipid levels, size of visceral-fat adipocytes, and
      mRNA levels of genes related to lipid metabolism were measured in control rats
      fed standard chow and in obesity-prone (high-fat-diet-induced obesity, DIO) and
      DR rats fed a high-fat diet. Glucose tolerance and insulin tolerance tests were
      also performed. RESULTS: DIO rats gained weight more rapidly than did DR and
      control rats; DR rats gained less weight than did DIO rats despite similar energy
      intake. Energy expenditure did not differ among the three groups. The diameter of
      visceral-fat adipocytes was similar in DR and control rats. mRNA levels of genes
      involved in lipogenesis, such as fatty acid synthase and acetyl-CoA carboxylase,
      tended to be lower in DR than in control and DIO rats, whereas those of carnitine
      palmitoyltransferase 1a, which is involved in fatty acid beta-oxidation, were
      greater in DR rats than in the other groups. DIO rats showed hyperinsulinemia and
      glucose intolerance, whereas DR rats had high sensitivity to insulin. CONCLUSION:
      DR rats show suppression of lipogenesis and acceleration of fatty acid beta
      oxidation in the visceral fat. These characteristics likely contribute to the
      anti-obesity phenotype of DR rats.

PMID- 24306152
TI  - Hypothalamic prepro-orexin mRNA level is inversely correlated to the non-rapid
      eye movement sleep level in high-fat diet-induced obese mice.
AB  - Orexins are hypothalamic neuropeptides, which play important roles in the
      regulation and maintenance of sleep/wakefulness states and energy homeostasis. To
      evaluate whether alterations in orexin system is associated with the
      sleep/wakefulness abnormalities observed in obesity, we examined the mRNA
      expression of prepro-orexin, orexin receptor type 1 (orexin 1r), and orexin
      receptor type 2 (oxexin 2r) in the hypothalamus in mice fed with a normal diet
      (ND) and high-fat diet (HFD)-induced obese mice. We also compared their
      relationships with sleep/wakefulness. Twenty-four, 4-week-old, male C57BL/6J mice
      were divided randomly into three groups, which received the following: (1) ND for
      17 weeks; (2) HFD for 17 weeks; and (3) ND for 7 weeks and HFD for a further 10
      weeks. The body weights of mice fed the HFD for 10-17 weeks were 112-150% of the
      average body weight of the ND group. The daily amount of non-rapid eye movement
      (NREM) sleep increased significantly in HFD-fed mice. These changes were
      accompanied by increases in the number but decreases in the duration of each NREM
      sleep episode. In addition, brief awakenings (<20 s epoch) during NREM sleep was
      nearly 2-fold more frequent. The mRNA level of prepro-orexin in the hypothalamus
      was significantly reduced in HFD-induced obese mice, whereas the levels of orexin
      1r and orexin 2r were unaffected. The daily amount of NREM sleep was negatively
      correlated with the hypothalamic prepro-orexin mRNA level, so these results
      suggest that the increased NREM sleep levels in HFD-induced obese mice are
      attributable to impaired orexin activity.

PMID- 24306154
TI  - Reduction in cardiovascular risk factors and insulin dose, but no beta-cell
      regeneration 1 year after Roux-en-Y gastric bypass in an obese patient with type
      1 diabetes: a case report.
AB  - Experience with Roux-en-Y gastric bypass in patients with type 1 diabetes is very
      limited, despite an increasing prevalence of obesity also in this population. We
      describe changes in anthropometric measures, insulin dose, HbA1c, blood pressure,
      lipid status, and metabolic response to a liquid mixed meal throughout the first
      year after RYGB in an obese patient with type 1 diabetes. No change in HbA1c was
      observed, but a 48% reduction in weight-adjusted insulin dose and improvements in
      cardiovascular risk factors was seen 1 year after surgery. Exaggerated secretions
      of anorexigenic gut hormones were seen during the meals.

PMID- 24306153
TI  - Comparative effectiveness of bariatric surgery vs. nonsurgical treatment of type
      2 diabetes among severely obese adults.
AB  - Although all weight-loss approaches may improve insulin sensitivity in type 2
      diabetes, bariatric surgery is believed to be the only reliable means of
      achieving diabetes remission. We conducted a retrospective cohort study to
      compare rates of diabetes remission, relapse and all-cause mortality among
      severely obese individuals with diabetes who underwent bariatric surgery vs.
      nonsurgically treated individuals. Severely obese adults with uncontrolled or
      medication-controlled diabetes who underwent bariatric surgery or received usual
      medical care from 2005 to 2008 in three health care delivery systems in the
      United States were eligible. Diabetes status was identified using pharmacy,
      laboratory, and diagnosis information from electronic medical records. A
      propensity approach and exclusion criteria identified 1395 adults with diabetes
      who had bariatric surgery and 62,322 who did not. Most procedures were Roux-en-Y
      gastric bypass (72.0% laparoscopic; 8.2% open); 4.4% were gastric banding, 2.4%
      sleeve gastrectomy, and 13.2% were other procedures. At two years, bariatric
      subjects experienced significantly higher diabetes remission rates [73.7% (95%
      CI: 70.6, 76.5)] compared to nonsurgical subjects [6.9% (95%CI: 6.9, 7.1)]. Age,
      site, duration of diabetes, hemoglobin A1c level, and intensity of diabetes
      medication treatment were significantly associated with remission. Bariatric
      subjects also experienced lower relapse rates than nonsurgical subjects (adjusted
      HR: 0.19; 95% CI: 0.15-0.23) with no higher risk of death (adjusted HR: 0.54; 95%
      CI: 0.22-1.30). We conclude that bariatric surgery can effectively induce
      remission of diabetes among most severely obese adults, and this treatment
      approach appears to be superior to nonsurgical treatment in inducing diabetes
      remission.

PMID- 24306155
TI  - Low 25-hydroxyvitamin D level is associated with insulin sensitivity in obese
      adolescents with non-alcoholic fatty liver disease.
AB  - AIM: The aim of this study was to investigate the relationships between 25
      hydroxy-vitamin D (25(OH)D) and insulin resistance in obese adolescents with non
      alcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: Eighty-seven obese
      adolescents (45 girls and 42 boys, mean age: 12.7 +/- 1.3 years, mean body mass
      index standard deviation score (BMI-SDS): 2.1 +/- 0.3) and 30 lean subjects (15
      girls and 15 boys, mean age: 12.3 +/- 1.45 years, mean BMI-SDS: 0.5 +/- 0.7) were
      enrolled for the study. The obese subjects were divided into two subgroups based
      on the presence or absence of fatty liver with high transaminases (NAFLD group
      and non-NAFLD group). Fasting blood samples were assayed for 25(OH)D,
      transaminases, glucose, and insulin levels. Insulin resistance was calculated by
      the homeostasis model assessment (HOMA-IR). RESULTS: 25(OH)D measurements were
      decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the lean
      group (29.5 +/- 18.4 vs. 41.0 +/- 17.9 vs. 48.1 +/- 22.2 ng/mL). However; the
      NAFLD group had significantly lower measurements of 25(OH)D than the non-NAFLD
      group (p < 0.001) and lean group (p < 0.001). 25(OH)D was negatively correlated
      with HOMA-IR (r = 0.158, p = 0.01) and with alanine aminotransferase (r = 0.794,
      p = 0.03) in the NAFLD obese group. There was no significant associations between
      fasting insulin, BMI-SDS and 25(OH)D in obese groups. CONCLUSION: We suggest that
      low 25(OH)D occurs commonly in obese adolescents with NAFLD and we demonstrated
      an association between insufficient vitamin D status and low insulin sensitivity
      in obese adolescents with NAFLD.

PMID- 24306156
TI  - Prevalence of elevated blood pressure and its relationship with fat mass, body
      mass index and waist circumference among a group of Moroccan overweight
      adolescents.
AB  - This study aimed to estimate the prevalence of hypertension among a group of
      adolescents and to assess the relationship of systolic and diastolic blood
      pressure (SBP, DBP) with body fat mass (BFM), body mass index (BMI) and waist
      circumference (WC). A total of 167 subjects aged 11-17 years were recruited,
      29.3% and 12.6% were overweight and obese respectively. BMI, WC, SBP and DBP were
      determined using standardized equipment. BFM was estimated by the deuterium oxide
      dilution. Hypertension (HT) and prehypertension (pre-HT) were observed in 17.4%
      and 9.6%, of the study population, respectively. The prevalence of HT and pre-HT
      was significantly higher in boys and in overweight-obese groups (p = 0.044; p =
      0.003 respectively). Both SBP and DBP were significantly higher in overweight
      obese compared to healthy-weight groups (p < 0.001; p = 0.002 respectively). SBP
      was significantly higher in boys than girls (p = 0.013). With some exceptions,
      SBP and DBP were significantly correlated with BMI, WC and BFM in the study
      population and different weight-status groups of both genders. The relationship
      of blood pressure with BMI appeared to be more significant than with WC and BFM.
      The prevalence of hypertension was higher in boys than girls and in overweight
      obese than healthy-weight adolescents. Overall SBP and DBP were associated with
      BFM, BMI and WC. However, the strong association between these variables was seen
      in girls, and the greater risk of developing hypertension could be associated
      with increasing BMI.

PMID- 24306157
TI  - 2 years change of waist circumference and body mass index and associations with
      type 2 diabetes mellitus in cohort populations.
AB  - OBJECTIVE: Compare the association between 2 years change of waist circumference
      (WC) or body mass index (BMI) and incident type 2 diabetes mellitus (T2DM) in
      cohort populations. METHODS: Prospective cohort study, based on a baseline
      investigation from 1999, we conducted the first follow-up for subjects whose
      follow time met 2 years, and the second follow-up for subjects whose follow time
      met 5 years. Two years change of WC or BMI was measured by the D-value between
      baseline and the first follow up values. The association between 2 years change
      of WC or BMI and incident T2DM were analyzed by using Poisson regression model.
      RESULTS: Among 3461 participants without T2DM at baseline, 160 subjects developed
      T2DM during follow up period. Across quartiles of WC D-value, hazards ratio (HR)
      of incident T2DM increased, but there was no significant dose response
      relationship was found between BMI D-value and incident T2DM. Compared with
      subjects whose both WC and BMI were modified, there was no significant increase
      for T2DM risk in subjects whose WC was modified but BMI was not modified
      [HR(95%CI) = 1.66(0.70-3.97)], but the T2DM risk was significantly higher in
      subjects whose WC was not modified but BMI was modified [HR(95%CI) = 1.73(1.17
      2.54)]. CONCLUSIONS: WC change was a better predictor for incident T2DM than BMI
      change. Intervention programs designed to reduce WC through lifestyle
      modification, including physical activity and diet, may have significant public
      health significance in preventing incident T2DM.

PMID- 24306158
TI  - Association between body mass index and high-sensitivity C-reactive protein in
      male Japanese.
AB  - We divided subjects into hs-CRP of <=1.0 mg/l and >1.0 mg/l, and investigated the
      relationship between hs-CRP and basic attributes, lifestyle and health checkup
      test results. In particular, hs-CRP increased significantly as BMI increased, and
      hs-CRP of >1.0 mg/l was seen in about 40% of people with BMI of >=25 kg/m(2) and
      75% with BMI of >= 30 kg/m(2). Persons with 3 or more abnormalities in BMI, blood
      pressure, serum lipid and glucose were found in 20.0% of those with hs-CRP >1.0
      mg/l, while 4.3% in hs-CRP <= 1.0 mg/l. The present findings have suggested that
      hs-CRP > 1.0 mg/l can be an indicator for obesity-related risks in male Japanese.

PMID- 24306159
TI  - Sarcopenic obesity is closely associated with metabolic syndrome.
AB  - OBJECTIVES: Obesity is a risk factor for metabolic syndrome (MetS). We aimed to
      investigate whether sarcopenic obesity (SO) was associated with MetS. METHODS: A
      total of 600 community-dwelling males and females aged 63.6 +/- 10.1 years in
      Northern Taiwan were enrolled in this study. Sarcopenia was defined by the
      percentage of total skeletal mass (total skeletal muscle mass (kg)/weight (kg) x
      100). Cut-offs were established at <37% in men and <27.6% in women using the
      bioelectrical impedance analysis (BIA) method. Obesity was defined as body mass
      index (BMI) >=25 kg/m(2). MetS was defined by the consensus of National
      Cholesterol Education Program-Adult Treatment Panel III modified for Asians. The
      association between MetS and SO was examined using multivariate logistic
      regression analyses after controlling potential confounders. RESULTS: The SO
      group demonstrated a higher risk for MetS (odds ratio [OR] 11.59 [95% confidence
      interval [CI] 6.72-19.98]) than the obese group (7.53 [4.01-14.14]) and
      sarcopenic group (1.98 [1.25-3.16]). The individual components including waist
      circumference, serum triglycerides, high-density lipoprotein cholesterol (HDL-C),
      and fasting serum glucose were independently associated with SO. CONCLUSION: SO
      is a major risk factor for MetS. The BIA method and BMI can easily identify
      subjects at high risk for MetS. The underlying mechanism for the relationship
      between SO and MetS warrants further research.

PMID- 24306160
TI  - Comparison of lipid accumulation product with body mass index as an indicator of
      hypertension risk among Mongolians in China.
AB  - OBJECTIVE: To compare associations of lipid accumulation product (LAP) and body
      mass index (BMI) with risk of hypertension. METHODS: Demographic characteristics,
      blood pressure and body measurements were obtained, blood lipids and fast plasma
      glucose were examined, BMI and LAP were calculated for 2589 Mongolians. Multiple
      linear model and covariance analysis was used to analyze the relationship between
      LAP and blood pressure levels, multivariate logistic analysis was used to analyze
      the association between BMI and LAP and hypertension. RESULTS: LAP and BMI were
      all significantly higher in hypertensives than in normotensives in both genders.
      Multivariate adjusted mean levels of SBP and DBP increased with increased LAP and
      there was a linear association between LAP and blood pressure. LAP had a stronger
      association with risk of hypertension compared with BMI, linear trend between LAP
      and risks of hypertension was better than that between BMI and risks of
      hypertension in males. Compared to the first quartile, the odds ratios [95%
      confidence intervals (95% CIs)] of hypertension associated with the second, third
      and fourth quartiles of LAP were 1.85(1.23,2.79), 2.20(1.47,3.28),
      4.21(2.78,6.38) in males; compared to the first quartile, the odds ratios (95%
      CIs) of hypertension associated with the second, third and fourth quartiles of
      BMI were 0.93(0.62,1.38), 1.23(0.83,1.84), 2.80(1.86,4.21) in males. CONCLUSION:
      LAP was more closely associated with risk of hypertension than BMI in Mongolian
      males, this study suggested that LAP might be a preferred anthropometry
      measurement to predict risk of hypertension in males. Future prospective cohort
      studies should be conducted to test the causal relationship between LAP and the
      risk of hypertension in Mongolian population.

PMID- 24306161
TI  - Obesity indices and metabolic markers are related to hs-CRP and adiponectin
      levels in overweight and obese females.
AB  - Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP),
      decreased adiponectin levels, and impaired microvascular endothelial function
      compared to lean subjects. We investigated the relationships of serum hs-CRP,
      adiponectin and microvascular endothelial function with obesity indices and
      metabolic markers in overweight and obese female subjects. Anthropometric
      profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin
      levels, and microvascular endothelial function were measured in 91 female
      subjects. Microvascular endothelial function was determined using laser Doppler
      fluximetry and the process of iontophoresis. Mean age and body mass index (BMI)
      of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were
      positively correlated with weight, BMI, waist circumference, hip circumference,
      body fat and visceral fat. Adiponectin levels were positively correlated with
      insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip
      ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No
      relationship was seen between microvascular endothelial function and obesity
      indices, and metabolic markers. In overweight and obese female subjects, hs-CRP
      levels were correlated with obesity indices while adiponectin levels were
      inversely correlated with obesity indices and metabolic markers. No significant
      relationship was seen between microvascular endothelial function with obesity
      indices and metabolic markers including hs-CRP and adiponectin in female
      overweight and obese subjects.

PMID- 24306162
TI  - Dinuclear cobalt(II) and cobalt(III) complexes of bis-bidentate napthoquinone
      ligands.
AB  - The combination of bridging bis-bidentate redox-active ligands derived from 3,3
      bis-2-hydroxy-1,4-naphthoquinone (bhnqH2), ancillary ligands based on tris(2
      pyridylmethyl)amine (tpa) and cobalt salts has afforded a new family of dinuclear
      cobalt complexes. Compounds of the complexes [Co2(bhnq)(tpa)2](2+) (1),
      [Co2(bhnq)(Metpa)2](2+) (2), [Co2(bhnq)(Me2tpa)2](2+) (3)
      [Co2(bhnq)(Me3tpa)2](2+) (4), [Co2(bhnq)(tpa)2](4+) (5),
      [Co2(bhMenaph)(tpa)2](2+) (6) and [Co2(bhPronaph)(tpa)2](2+) (7) (Mentpa involves
      n = 0, 1, 2 and 3 methyl groups at the 6-position of the tpa pyridine rings;
      bhMenaphH4 = bis-3,4-dihydroxy-4-methoxynaphthalene-1-one; bhPronaphH4 = bis-3,4
      dihydroxy-4-(2-oxopropyl)naphthalen-1(4H)-one) have been characterised by single
      crystal X-ray diffraction. While complexes 1-4 possess divalent cobalt centres,
      trivalent cobalt is evident in complexes 5-7. The bis-bidentate redox-active
      bridging ligand remains in the diamagnetic quinone bhnq(2-) redox state in
      complexes 1-5. Metal-catalysed reaction with methoxide or acetone enolate ions
      gives rise to the derivatised bridging ligands present in 6 and 7. The electronic
      properties of compounds of 1-7 have been explored in the solid state by infrared
      spectroscopy and variable temperature magnetic measurements and in solution by
      electronic absorption spectroscopy and cyclic voltammetry. 

PMID- 24306163
TI  - Prolonged preoperative chemotherapy for locally advanced pancreatic
      adenocarcinoma: curing cancer or simply improving patient selection?

PMID- 24306164
TI  - A multi-centred audit of secondary spinal assessments in a trauma setting: are we
      ATLS compliant?
AB  - PURPOSE: The global incidence of spinal cord injuries varies with the developed
      world having improved survival and 1 year mortality in a poly-trauma setting.
      This improved survival has been estimated at 20 % in a recent Cochrane review of
      Advanced Trauma Life Support (ATLS).The aim of this audit is to evaluate the
      management of patients with suspected spinal cord injury by the trauma and
      orthopaedic team in three centres in South Wales. METHODS: A retrospective case
      note review of the secondary survey was performed. Inclusion criteria were
      patients 18 years and above, with poly-trauma and presenting to Accident and
      Emergency department at the treating hospital. We used ATLS guidelines as an
      audit tool and reviewed the documentation of key components of the secondary
      assessment. RESULTS: Forty-nine patients were included (29 males, 20 females)
      with an average age of 53.7 years (19-92 years). We found that completion of all
      components of the secondary survey for spinal injury was poor, 29 % receiving a
      digital per rectal examination despite suspected spinal injury. Paralysis level
      was not documented in 20.4 % of patients. Medical Research Council grade was only
      documented in 24.5 % although was assessed in 73.5 %. The secondary survey took
      place after 2 h in 54.6 % of patients. CONCLUSION: We found that the
      documentation of the performance of a secondary survey was poor. We found that
      most patients included in this study are not currently meeting the minimal
      standard suggested by the ATLS guidelines.

PMID- 24306165
TI  - Comparison of vertebroplasty and kyphoplasty in the treatment of osteoporotic
      vertebral compression fractures with intravertebral clefts.
AB  - BACKGROUND: Few studies have compared the surgical outcomes of vertebroplasty
      (VP) and kyphoplasty (KP) in the treatment of osteoporotic vertebral compression
      fractures (VCFs) with intravertebral clefts. METHODS: A retrospective study was
      conducted to review patients with a single-level osteoporotic VCF treated by VP
      or KP. Intravertebral clefts were assessed by preoperative computed tomography
      (CT) and magnetic resonance scans. All enrolled patients were followed up for 12
      months. Clinical outcomes, radiological findings and complications were
      evaluated. RESULTS: A total of 53 patients were available for data analysis. Most
      of the fractures (75.5 %) occurred in the region of the thoracolumbar junction
      (T10-L2). Twenty-four patients received VP and 29 patients received KP. Patients
      in both group had significant pain relief after surgery (P < 0.01). Compared with
      VP group, there was a significant lower visual analogue scale (VAS) score in KP
      group at the 6- (P = 0.04) and 12-month follow-up (P = 0.02), but the decreased
      values of VAS score had no significant correlation with the magnitude of
      deformity correction. Restoration of vertebral body height and reduction in
      kyphotic angle were achieved in both groups, and the magnitude of correction was
      more significant in KP group (P < 0.01). Cement leakage rate in VP group (66.7 %)
      was higher than that in KP group (20.7 %), and there was a significant difference
      (P < 0.01). CONCLUSIONS: Intravertebral clefts occur primarily at the
      thoracolumbar junction and can be detected easily by CT and magnetic resonance
      imaging scans. Both VP and KP are effective in the treatment of clefts, but
      patients in KP group tend to have a better pain relief at the medium and long
      term follow-up. However, the better pain relief effect of KP cannot be attributed
      to the higher magnitude of deformity correction.

PMID- 24306166
TI  - A retrospective study of treating thoracolumbar spine fractures in ankylosing
      spondylitis.
AB  - Spinal fractures are commonly encountered in ankylosing spondylitis (AS)
      patients. This study compares the outcome of early surgical treatment with
      initial conservative treatment for thoracolumbar fractures in patients with AS.
      From 1996 to 2008, 28 patients with AS were treated either operatively or
      conservatively for thoracolumbar fractures; however, only 25 patients met the
      inclusion criteria with a minimum follow-up of 2 years. For surgically treated
      patients, posterior spinal instrumentation was performed using a transpedicle
      screw system. Nonsurgically treated patients wore a fracture brace. The
      demographic data, diagnosis, mechanism of injury, and neurological status were
      recorded, and fracture healing was assessed radiographically. The mean age was
      54.2 +/- 13.8 years (range 30-80 years). Six patients (Group A) received surgical
      intervention within 1 month. All of these fractures healed, and two of five
      patients showed neurologic improvement after surgery. Eight patients (Group B)
      had fractures that were missed. The delay in diagnosis resulted in
      pseudoarthrosis in all cases, and progressive neurologic deficits were identified
      in four cases. Eleven patients (Group C) received conservative treatment with
      bracing. Fracture union was achieved in three cases, and pseudoarthrosis occurred
      in eight cases. Operative treatment can achieve solid fusion and improve the
      neurological status, while conservative treatment may result in pseudoarthrosis
      and progressive neurologic deficit. The results suggest that AS patients with
      unstable spinal fractures should receive early surgical management to prevent
      further sequelae. 

PMID- 24306167
TI  - Two-stage revision for infected total knee arthroplasty: our experience with
      interval prosthesis.
AB  - INTRODUCTION: To review our practice of performing two-stage revision for
      infected total knee arthroplasty using articulating interval prosthesis and to
      compare the incidence of the recurrence of infection and re-operation rate in
      patients undergoing two-stage revision as planned with the group of patients who
      choose not to proceed to the second stage. METHOD: This study is a retrospective
      review of 60 consecutive patients undergoing a two-stage revision for infected
      total knee arthroplasty using articulating interval prosthesis. All cases managed
      by a single surgeon using a uniform peri-operative protocol, and short-course
      parenteral antibiotic therapy. RESULT: Thirty-four patients (57%) (Group 1)
      underwent the two-stage revision as planned. However, twenty-six patients (43%)
      (Group 2) opted not to have a second-stage procedure as the first-stage and
      interval prosthesis had eradicated the infection, resolved the pain and achieved
      good functional outcome. There were five cases of recurrent infection in the 60
      patients (8%) at a mean follow-up 5 years. In those completing the two-stage
      revision, two patients had recurrent infection. Of the patients who retained the
      interval prosthesis, there were three recurrent infections. There was no
      statistically significant difference between the groups in terms of recurrence of
      infection or re-revision. CONCLUSION: Two-stage revision with interval prostheses
      represents a safe and reliable method of treating infected knee prosthesis;
      however, there may be a role for one-stage revision in selected cases.

PMID- 24306168
TI  - Antegrade rigid nailing through the tip of the greater trochanter for pediatric
      femoral shaft fractures.
AB  - The aim of this work was to evaluate the results of rigid nailing of pediatric
      femoral shaft fractures inserted antegrade through the tip of the greater
      trochanter. Twenty-three femoral shaft fractures in 23 children were fixed with
      rigid interlocking nails inserted through the tip of the greater trochanter at
      Mansoura Emergency Hospital in the period between June 2009 and August 2011. The
      average age of the patients at the time of injury was 12.6 years (range 9.2-15
      years). The final follow-up radiographs were assessed for evidence of avascular
      necrosis (AVN) of the femoral head and any deformity of the proximal femur, the
      neck-shaft angle, the articulotrochanteric distance, and the femoral neck
      diameter. Patients were followed to a mean period of 31 months (range from 25 to
      36 months) postoperatively. All fractures united in a range of 9 weeks (from 8 to
      13 weeks) with no limb length discrepancy more than 2 cm and no clinically
      evident rotation in either direction; no case had a vascular necrosis of the
      femoral head or significant proximal femoral deformity by the final follow-up.
      Fixation of fractures of the shaft of the femur in children with rigid
      interlocking nails inserted through the tip of the greater trochanter is a rigid
      way for fixation controlling rotation and length. It is a safe technique without
      causing AVN of the femoral head or proximal femoral deformity.

PMID- 24306169
TI  - Radiographic assessment of ligamentous injuries in distal radius fractures after
      open reduction and internal fixation.
AB  - OBJECTIVES: Concomitant ligamentous injury in distal radius fractures (DRF) may
      explain continued pain following surgery. The purpose of this study was to
      compare radiographic measurements assessing scaphoid translation in DRF after
      reduction, to measurements performed on normal radiographs. This may allow
      noninvasive evaluation of radiocarpal ligamentous integrity. METHODS: Fifty
      postoperative radiographs were evaluated. The distance between the ulnar border
      of the radial styloid and the radial border of the scaphoid was measured midway
      between the styloid tip and scaphoid base, and then divided by scaphoid width at
      the same level. The measured ratios were compared to previously established
      normal data, established radiographic measurements of fracture reduction,
      fracture characteristics and fixation methods. RESULTS: Radiographic scaphoid
      position measurements differed significantly from normals (p = 0.0001). Fracture
      characteristics, surgical difficulty, and technique were not associated with
      scaphoid position. CONCLUSIONS: Despite accurate surgical reduction, abnormal
      positioning of the scaphoid may persist. This may reflect ligamentous injury,
      which generates suboptimal clinical results. Identifying and addressing
      ligamentous injury during surgery may prevent the development of instability and
      improve outcome after DRF.

PMID- 24306171
TI  - The importance of ignorance.

PMID- 24306172
TI  - The physician as priest, revisited.
AB  - Despite much resistance from the medical profession, the notion persists in our
      culture that the physician plays a priestly role. Medical resistance must be
      taken seriously. It stems from legitimate concerns that the priestly role implies
      an unwelcome broadening of medical responsibilities, expectations of moral
      expertise, and being on the receiving end of people's most intense existential
      hopes. On the other hand, the nature of illness and healing makes it inevitable
      that physicianswill take on ministerial functions in their medical work. This
      essay attempts to recover the notion of the physician as priest on the basis of
      theological and religious reflection on the nature of ministry and pastoral care.

PMID- 24306173
TI  - Communicating fundamentals of water and sanitation in Moslem communities.
AB  - According to the World Health Organization, 80 percent of all human diseases in
      the Third World relate to inadequate sanitation and the lack of clean water.
      Moreover, the incidence of these water-borne diseases shows no sign of
      diminishing, despite the installation of improved water systems in many rural
      communities. The beneficiaries of these systems, and particularly the women,
      remain as unaware of the benefits of improved water use and sanitation practices
      as they are of the germ theory of disease causation. Accordingly, this paper
      suggests the use of a community's existing values and belief structures in
      developing a strategy for communicating the need of behavioral change in water
      and sanitation practice. The author discusses how Koranic religious values can
      help promote this change, and suggests an operational strategy for use by
      international agencies in Moslem communities. 

PMID- 24306174
TI  - The escape-to-Israel syndrome: Variations on the geographic cure.
AB  - The author conceptualizes a pattern of thought and behavior that can be called
      the escape-to-Israel syndrome. This pattern is a contemporary variety, appearing
      primarily in the Jewish population, of the "geographic cure": that is, one can
      solve one's personal dilemmas by moving from one place to another. The syndrome
      is characterized by a tendency to idealize life in Israel. This idealization, and
      the viewers' fantasy of their own future in Israel, deflect solid confrontation
      with genuine personal problems. If, in fact, they do move to Israel, they may
      experience shock and trauma at the gap between expected reality and the
      discovered one. This may only compound their emotional difficulties. 

PMID- 24306175
TI  - A reappraisal of Teresa of Avila's supposed hysteria.
AB  - This essay offers a reassessment of Teresa's severe seizures which were such a
      characteristic feature of her mysticism. The diagnosis of hysteria is no longer
      viable, at the very least given its abandonment by clinicians. An alternative
      analysis is developed by phenomenologically comparing Teresa's seizures to
      parallel experiences of subjects in LSD-assisted psychotherapy. Using Stanislav
      Grof's categories, it is argued that Teresa's seizures are perinatal symptoms. As
      such, they represent the emergence and reintegration of extremely primitive
      psychological systems and might be described as the growing pains of
      transpersonal consciousness. They reflect not degenerative psychopathology but
      progressive movement toward higher states of consciousness. 

PMID- 24306170
TI  - Factors affecting formation and rupture of intracranial saccular aneurysms.
AB  - Unruptured intracranial aneurysms represent a decisional challenge. Treatment
      risks have to be balanced against an unknown probability of rupture. A better
      understanding of the physiopathology is the basis for a better prediction of the
      natural history of an individual patient. Knowledge about the possible
      determining factors arises from a careful comparison between ruptured versus
      unruptured aneurysms and from the prospective observation and analysis of
      unbiased series with untreated, unruptured aneurysms. The key point is the
      correct identification of the determining variables for the fate of a specific
      aneurysm in a given individual. Thus, the increased knowledge of mechanisms of
      formation and eventual rupture of aneurysms should provide significant clues to
      the identification of rupture-prone aneurysms. Factors like structural vessel
      wall defects, local hemodynamic stress determined also by peculiar geometric
      configurations, and inflammation as trigger of a wall remodeling are crucial. In
      this sense the study of genetic modifiers of inflammatory responses together with
      the computational study of the vessel tree might contribute to identify aneurysms
      prone to rupture. The aim of this article is to underline the value of a unifying
      hypothesis that merges the role of geometry, with that of hemodynamics and of
      genetics as concerns vessel wall structure and inflammatory pathways. 

PMID- 24306176
TI  - Energy and psychical pain.
AB  - Several relationships between energy and psychical pain are developed in this
      paper. These concepts are a-structural and existential in spirit, although
      developed in the framework of some analytic formulations on personality. A key
      concept developed is that the nature of psychical pain is determined, in part, by
      the manner in which the state of psychical energy associated with the pain
      departs from a given healthy ideal. 

PMID- 24306177
TI  - Single-phased white-light-emitting NaCaBO3:Ce3+,Tb3+,Mn2+ phosphors for LED
      applications.
AB  - A series of NaCaBO3:Ce(3+),Tb(3+),Mn(2+) borate phosphors were prepared via a
      high-temperature solid-state reaction. The obtained phosphors exhibit a strong
      excitation band between 250 and 400 nm, matching well with the dominant emission
      band of a NUV light-emitting-diode (LED) chip. The phosphors can generate light
      from blue to green, and from blue to red by Ce(3+)->Tb(3+) and Ce(3+)->Mn(2+),
      respectively. Furthermore, a wide-range-tunable white light emission was obtained
      by precisely controlling the contents of Ce(3+), Mn(2+), Tb(3+). The results show
      that this phosphor has potential applications as a single-phased phosphor for NUV
      white LEDs. 

PMID- 24306178
TI  - Individuals with coronary artery disease at a young age and features of the
      metabolic syndrome have an increased prothrombotic potential.
AB  - The relation between coagulation and atherosclerosis has been extensively
      described, pointing towards a hypercoagulable state in patients with
      atherosclerosis, especially in young individuals. However, not all studies were
      conclusive. It is known that the metabolic syndrome (MetS), a risk factor for
      coronary artery disease (CAD), is related to a higher incidence of thrombo
      embolic events. We hypothesised that individuals with CAD at a young age and MetS
      have an increased prothrombotic potential. It was the study objective to analyse
      the endogenous thrombin potential (ETP) and related thrombin generation
      parameters in patients with CAD before the age of 51 in men and 56 in women with
      and without MetS features and their healthy first-degree relatives. In this case
      control study we included 118 CAD patients and 50 first-degree relatives
      (controls). Parameters of thrombin generation were obtained with calibrated
      automated thrombinography. An adjusted general linear model (GLM) showed a
      positive association between the peak thrombin levels and the presence of CAD at
      a young age. Based on the NCEP criteria we divided our patient group in CAD
      patients with and without MetS, and compared them to the controls without MetS.
      We showed that CAD patients with MetS have increased ETP levels, both in
      comparison with healthy first-degree relatives and with CAD patients without
      MetS. There were no differences in ETP between patients without MetS and healthy
      controls. In conclusion, this study shows that individuals with CAD at a young
      age and MetS features have an increased prothrombotic potential, compared to CAD
      patients without MetS. 

PMID- 24306179
TI  - [Winter sport injuries].

PMID- 24306180
TI  - Detection and characterization of serine and threonine hydroxyl protons in
      Bacillus circulans xylanase by NMR spectroscopy.
AB  - Hydroxyl protons on serine and threonine residues are not well characterized in
      protein structures determined by both NMR spectroscopy and X-ray crystallography.
      In the case of NMR spectroscopy, this is in large part because hydroxyl proton
      signals are usually hidden under crowded regions of (1)H-NMR spectra and remain
      undetected by conventional heteronuclear correlation approaches that rely on
      strong one-bond (1)H-(15)N or (1)H-(13)C couplings. However, by filtering against
      protons directly bonded to (13)C or (15)N nuclei, signals from slowly-exchanging
      hydroxyls can be observed in the (1)H-NMR spectrum of a uniformly (13)C/(15)N
      labeled protein. Here we demonstrate the use of a simple selective labeling
      scheme in combination with long-range heteronuclear scalar correlation
      experiments as an easy and relatively inexpensive way to detect and assign these
      hydroxyl proton signals. Using auxtrophic Escherichia coli strains, we produced
      Bacillus circulans xylanase (BcX) labeled with (13)C/(15)N-serine or (13)C/(15)N
      threonine. Signals from two serine and three threonine hydroxyls in these protein
      samples were readily observed via (3)JC-OH couplings in long-range (13)C-HSQC
      spectra. These scalar couplings (~5-7 Hz) were measured in a sample of uniformly
      (13)C/(15)N-labeled BcX using a quantitative (13)C/(15)N-filtered spin-echo
      difference experiment. In a similar approach, the threonine and serine hydroxyl
      hydrogen exchange kinetics were measured using a (13)C/(15)N-filtered CLEANEX-PM
      pulse sequence. Collectively, these experiments provide insights into the
      structural and dynamic properties of several serine and threonine hydroxyls
      within this model protein.

PMID- 24306181
TI  - Paramagnetic doping of a 7TM membrane protein in lipid bilayers by Gd3+-complexes
      for solid-state NMR spectroscopy.
AB  - A considerable limitation of NMR spectroscopy is its inherent low sensitivity.
      Approximately 90 % of the measuring time is used by the spin system to return to
      its Boltzmann equilibrium after excitation, which is determined by (1)H-T1 in
      cross-polarized solid-state NMR experiments. It has been shown that sample doping
      by paramagnetic relaxation agents such as Cu(2+)-EDTA accelerates this process
      considerably resulting in enhanced sensitivity. Here, we extend this concept to
      Gd(3+)-complexes. Their effect on (1)H-T1 has been assessed on the membrane
      protein proteorhodopsin, a 7TM light-driven proton pump. A comparison between
      Gd(3+)-DOTA, Gd(3+)-TTAHA, covalently attached Cu(2+)-EDTA-tags and Cu(2+)-EDTA
      reveals a 3.2-, 2.6-, 2.4- and 2-fold improved signal-to-noise ratio per unit
      time due to longitudinal paramagnetic relaxation enhancement. Furthermore, Gd(3+)
      DOTA shows a remarkably high relaxivity, which is 77-times higher than that of
      Cu(2+)-EDTA. Therefore, an order of magnitude lower dopant concentration can be
      used. In addition, no line-broadening effects or peak shifts have been observed
      on proteorhodopsin in the presence of Gd(3+)-DOTA. These favourable properties
      make it very useful for solid-state NMR experiments on membrane proteins.

PMID- 24306182
TI  - Tilting at windmills: a comment on Auer and Griffiths.
AB  - In their review of Internet gambling studies, Auer and Griffiths (Soc Sci Comput
      Rev 20(3):312-320, 2013) question the validity of using bet size as an indicator
      of gambling intensity. Instead, Auer and Griffiths suggest using "theoretical
      loss" as a preferable measure of gambling intensity. This comment identifies
      problems with their argument and suggests a convergent rather than an
      exclusionary approach to Internet gambling measures and analysis. 

PMID- 24306185
TI  - An ATP-synthesizing system in seeds.
AB  - Using onion seed powder, a semi-in vitro system for ATP synthesis in seeds has
      been developed. The system requires AMP, phosphoenolpyruvate (PEP) and
      orthophosphate with apparent Km values of 0.8, 1.5 and 3.0 mM, respectively. ATP
      synthesis is pH-dependent with a sharp optimum at pH 6.4, it exhibits linearity
      with time up to 40 min, and with a seed powder concentration between 25 and 150
      mg ml(-1). The system is stimulated by low concentrations (<25 mM) of K(+) and
      Mg(2+) but is inhibited by higher concentrations of K(+) and Mg(2+) as well as by
      low concentrations of Li(+), Na(+) and especially Ca(2+). The maximal rate is
      about 5 pmol min(-1) mg seed powder(-1) in dry onion seeds. During seed
      imbibition the rate of activity increases by about 120% after 3 h, reaching a
      plateau which is steady up to 18 h, when the radicle emerges. A comparison of the
      ATP content in seeds during the early period of imbibition with the capacity of
      ATP synthesis at this stage reveals that the described system could provide,
      during germination, 100 times more ATP than that found in imbibed seeds. The
      system is shown to be present in ten different types of seeds. 

PMID- 24306184
TI  - Efficacy of the combination of voriconazole and caspofungin in experimental
      pulmonary aspergillosis by different Aspergillus species.
AB  - OBJECTIVES: Invasive pulmonary aspergillosis (IPA) caused by Aspergillus
      fumigatus, Aspergillus flavus, or Aspergillus niger is associated with high
      mortality. We evaluated the efficacy and compared the therapeutic effect
      differences of voriconazole (VRC) in combination with caspofungin (CAS) in
      transiently neutropenic rats infected by A. fumigatus, A. flavus, or A. niger.
      METHODS: Treatment groups consisted of VRC (10 mg/kg q12 h) monotherapy, CAS (1
      mg/kg/day) monotherapy, combination of VRC (10 mg/kg q12 h) + CAS (1 mg/kg/day),
      and no drug for 10 consecutive days. The efficacy and the difference in the
      treatments were evaluated through prolongation of survival, reduction in serum
      galactomannan levels and residual fungal burden, and histological studies.
      RESULTS: For all the strains, the combination of VRC and CAS led to significant
      prolongation in survival (P < 0.05) and reduction in residual fungal burden (P <
      0.05) compared with CAS alone, and decrease in serum galactomannan levels (P <
      0.05) compared with either agent alone. The survival in the combined therapy
      groups was significantly improved compared to VRC monotherapy for the strains of
      A. flavus and A. niger (P < 0.05), but no significant difference for the strains
      of A. fumigatus (P > 0.05). CONCLUSIONS: Combination of VRC and CAS was
      synergistic in IPA by A. flavus and A. niger, but small efficacy benefits in IPA
      by A. fumigatus.

PMID- 24306183
TI  - Breaking and entering into the CNS: clues from solid tumor and nonmalignant
      models with relevance to hematopoietic malignancies.
AB  - Various malignancies invade the CNS sanctuary site, accounting for the vast
      majority of CNS neoplastic foci and contributing to significant morbidity as well
      as mortality. The blood-brain barrier (BBB) exhibits considerable impermeability
      to chemotherapeutic agents, severely limiting therapeutic options available for
      patients developing metastatic CNS involvement, accounting for poor outcomes. The
      mechanisms by which malignant cells breach the highly exclusive BBB and
      subsequently survive in this unique anatomical site remain poorly understood,
      with most of the current knowledge stemming from nonmalignant and solid
      malignancy models. While solid and hematologic malignancies may face different
      challenges once within the CNS (e.g., solid tumor parenchymal metastasis compared
      to masses/nodules/leptomeningeal disease in hematologic malignancies),
      commonality exists in the process of migrating across the BBB from the
      circulation. Specifically considering this last point, this review aims to survey
      the current mechanistic knowledge regarding malignant migration across the BBB,
      necessarily emphasizing the better studied solid tumor and nonmalignant models
      with the intention of highlighting both the current knowledge gap and additional
      work required to effectively consider how hematopoietic malignancies breach the
      CNS. 

PMID- 24306186
TI  - Nutritional requirements of protoplast-derived, haploid tobacco cells grown at
      low cell densities in liquid medium.
AB  - Preliminary attempts to define a completely synthetic medium able to support
      divisions of haploid tobacco mesophyll protoplasts at low initial densities have
      failed. High protoplast concentrations together with large amounts of
      naphtaleneacetic acid in the medium (3 mg l(-1) NAA) were required for maximal
      induction of protoplast division. However, cell suspensions derived from haploid
      protoplasts after four days of preculture at high initial cell densities could be
      diluted to densities as low as 1-4 cells ml(-1), provided the concentration of
      NAA in the medium was lowered to below 0.3 mg l(-1). The optimal NAA supply for
      low cell density growth was affected by the nature of the nitrogen source.A
      simple minimal medium which supports the growth of these haploid cells with a
      plating efficiency of 30-40%, independent of the cell density in the range of 1-4
      to 3.10(4) cells ml(-1), has been established. In this medium inositol was the
      only vitamin stringently required for growth.Growth of cells at low densities was
      also possible in a medium initially containing 3 mg l(-1) NAA, provided it was
      conditioned by the growth of protoplasts at high densities. Preliminary
      experiments with [(14)C]NAA showed that the amount of free NAA remaining in the
      medium after preincubation at high densities was drastically reduced.
      Simultaneously, NAA conjugates accumulated in the medium. The implications of
      these results are discussed. 

PMID- 24306187
TI  - Comparative electrophoretic study on ribosomal proteins from algae.
AB  - The proteins from cytoplasmic ribosomal subunits of eight species of algae were
      analyzed by two-dimensional gel electrophoresis. The molecular weights of the
      proteins were in the range of 10,000 to 55,000. We have compared the protein
      patterns from the ribosomal subunits of the different species to those of
      Chlamydomonas reinhardii. It was quite clear that there are many similarities in
      the protein patterns of all the investigated species. We found for Chlamydomonas
      eugametos 48, Chlamydomonas noctigama 42, Chlorogonium elongatum 47, Scenedesmus
      obliquus 40, Chlorella fusca 35, and Euglena gracilis 35 proteins which were
      homologous to those of Chlamydomonas reinhardii. For the colorless flagellate
      Polytoma papillatum, we detected 45 proteins homologous to Chlamydomonas
      reinhardii, so that the generally assumed close relationship between
      Chlamydomonas and Polytoma is confirmed. 

PMID- 24306188
TI  - Polyploidy and aspartate-transcarbamylase activity in Hippocrepis comosa L.
AB  - The DNA content of plants which were sampled in natural di-, tetra- and hexaploid
      populations of Hippocrepis comosa L. was estimated and the aspartate
      transcarbamylase activities of the corresponding cell-free extracts were
      compared. The amount of DNA is not exactly proportional to the number of genomes.
      The three kinds of populations do not differ in their aspartate transcarbamylase
      specific activity. While the enzyme properties are identical in the extracts
      derived from the diploid and hexaploid plants, the aspartate transcarbamylase
      present in the tetraploid cytotype shows a slightly lower affinity for one of its
      substrates and a significantly lower sensitivity to the feedback inhibitor UTP
      which is still observed after partial purification. These properties might be
      related to the previously reported greater ability of the tetraploid cytotype to
      adapt to a variety of biotopes. 

PMID- 24306189
TI  - Three chloroplast membrane models corresponding to different photosynthetic
      potentialities in the same plant.
AB  - The biochemical characteristics and photosynthetic activities of chloroplast
      membranes of the two regions of the green tomato fruit were compared to those of
      the leaves which were taken as controls. Membranes may have qualitatively (and
      even quantitatively) identical components, such as lipids and chlorophylls, and
      yet have different photosynthetic abilities. Three models then are proposed. 

PMID- 24306190
TI  - Characterization of a cytoplasmic auxin receptor from tobacco-pith callus.
AB  - Cultured tobacco-pith tissue contains a cytoplasmic receptor for indoleacetic
      acid (IAA). The concentration of binding sites is very low in comparison to that
      of several auxin receptors found by other investigators. A few obvious possible
      causes (degradation or inactivation) were investigated. From the results we
      conclude that the low number of binding sites is real. The receptor binds IAA
      optimally at pH 7.5-7.8 and at a temperature of 24-30 degrees C, when incubated
      for 25-30 min. The binding is very specific, as is shown by competition
      experiments. The concentration of the receptor in the callus tissue changes
      dramatically during each culture period, which suggests a possible role in
      development. The receptor was partly purified by gel filtration on Sepharose 6B
      followed by ion-exchange chromatography on DEAE-cellulose. 

PMID- 24306191
TI  - The mechanism of the control of carbon fixation by the pH in the chloroplast
      stroma : Studies with acid mediated proton transfer across the envelope.
AB  - The salts of several weak acids have been used to render the envelope permeable
      to protons. In order to investigate the role of stromal pH changes in the light
      regulation of CO2 fixation, formate, octanoate, nitrite, and glyoxylate have been
      tried as tools to reverse the light-dependent alkalization of the stroma. For
      this purpose, the decrease of the stromal pH in illuminated spinach chloroplasts,
      as caused by the addition of these substances or by instantaneous lowering of the
      pH in the medium, has been compared with the corresponding decrease of CO2
      fixation and the change of stromal metabolite levels. It appears from out data
      that formate and octanoate are suited best to obtain a specific inhibition of CO2
      fixation by lowering the stromal pH. The measurement of the corresponding
      metabolite levels indicates that this inhibition is primarily due to an
      inhibition of fructose- and sedoheptulose bisphosphatase. It is concluded that
      these two enzymes are important regulatory steps for the light control of CO2
      fixation. 

PMID- 24306192
TI  - CO2 and malate metabolism in starch-containing and starch-lacking guard-cell
      protoplasts.
AB  - Isolated, purified mesophyll and guard-cell protoplasts of Vicia faba L. and
      Allium cepa L. were exposed to (14)CO2 in the light and in the dark. The guard
      cell protoplasts of Vicia and Allium did not show any labeling in phosphorylated
      products of the Calvin cycle, thus appearing to lack the ability to reduce CO2
      photosynthetically. In Vicia, high amounts of radioactivity (35%) appeared in
      starch after 60-s pulses of (14)CO2 both in the light and in the dark.
      Presumably, the (14)CO2 is fixed into the malate via PEP carboxylase and then
      metabolized into starch as the final product of gluconeogenesis. This is
      supported by the fact that guard-cell protoplasts exposed to malic acid uniformly
      labeled with (14)CO2 showed high amounts of labeled starch after the incubation,
      whereas cells labeled with [4-(14)C]malate had minimal amounts of labeled starch
      (1/120).In contrast, the starch-deficient Allium, guard-cell protoplasts did not
      show any significant (14)CO2 fixation. However, adding PEP to an homogenate
      stimulated (14)CO2 uptake, thus supporting the interpretation that the presence
      of starch as a source of PEP is necessary for incorporating CO2 and delivering
      malate. With starch-containing Vicia guard-cell protoplasts, the correlation
      between changes in volume and the interconversion of malate and starch was
      demonstrated. It was shown that the rapid gluconeogenic conversion of malate into
      starch prevents an increase of the volume of the protoplasts, whereas the
      degradation of starch to malate is accompanied by a swelling of the protoplasts. 

PMID- 24306193
TI  - Light-dependent net CO-evolution by C3 and C 4 plants.
AB  - Light-dependent CO-evolution by the green leaves of C3 and C4 plants depends on
      the CO2/O2 ratio in the ambient atmosphere. This and other physiological
      responses suggest that CO-evolution is a byproduct of photorespiration. At CO2/O2
      ratios up to 10(-3), the ratio of CO evolved: CO2 fixed in photosynthesis is
      significantly higher in C3 than in C4 plants. This discrepancy disappears when a
      correction is made for the CO2-concentrating mechanism in C4 photosynthesis, by
      which CO2-concentration at the site of ribulose-bis-phosphate
      carboxylase/oxygenase in the bundle sheaths is raised significantly as compared
      to the ambient atmosphere. Since the oxygenase function of this enzyme is
      responsible for glycolate synthesis, i.e., the substrate of photorespiration,
      this result seems to support the conclusion that CO-evolution is a consequence of
      photorespiration. CO-evolution may turn out to be a useful and rather
      straightforward indicator for photorespiration in ecophysiological studies. 

PMID- 24306194
TI  - D-Amino-acid-stimulated ethylene production in seed tissues.
AB  - Ethylene production by axial and cotyledonary tissues excised from Xanthium
      pennsylvanicum Wallr. seeds was markedly (up to 5-fold) stimulated by the D
      isomers of phenylalanine, valine, leucine, threonine, methionine and eithionine
      while the L-isomers caused no such effect. Responsiveness of these seed tissues
      to D-methionine appeared soon after the beginning of imbibition, reached a
      maximum after 6-12 and 12-24 h for the axial and cotyledonary tissues,
      respectively, and then decreased sharply. D-Phenylalanine and D-methionine also
      stimulated ethylene production in seed tissues of X. canadense Mill. and in
      cotyledonary segments from seeds of Helianthus annuus L., Cucurbita moschata
      Duch. and Vigna radiata (L.) Wilczek. The endogeneous ethylene production and the
      D-amino-acid-stimulated ethylene production by the seed segments was strongly
      inhibited by aminoethoxyvinyl glycine, a potent inhibitor of ethylene synthesis
      from L-methionine. 

PMID- 24306195
TI  - Properties of condensed chromatin in barley nuclei.
AB  - A method for isolation and purification of intact nuclei from barley leaves was
      developed and several properties of the chromatin were studied. The dense
      structure of the main part of the chromatin does not alter the accessibility of
      the DNA to nucleases. 60% of the nuclear DNA can be degraded by micrococcal
      endonuclease. Nevertheless the solubility of the chromatin fragments depends on
      the extent of nuclease digestion; solubilisation occurring only when the major
      part of the internucleosomal DNA was degraded (?30% of digestion). Electron
      microscopic observations suggest that this was due to particularly dense
      organization of the chromatin "in situ". The possible physiological meaning of
      some of these properties are discussed. 

PMID- 24306196
TI  - A biochemical model of photosynthetic CO2 assimilation in leaves of C 3 species.
AB  - Various aspects of the biochemistry of photosynthetic carbon assimilation in C3
      plants are integrated into a form compatible with studies of gas exchange in
      leaves. These aspects include the kinetic properties of ribulose bisphosphate
      carboxylase-oxygenase; the requirements of the photosynthetic carbon reduction
      and photorespiratory carbon oxidation cycles for reduced pyridine nucleotides;
      the dependence of electron transport on photon flux and the presence of a
      temperature dependent upper limit to electron transport. The measurements of gas
      exchange with which the model outputs may be compared include those of the
      temperature and partial pressure of CO2(p(CO2)) dependencies of quantum yield,
      the variation of compensation point with temperature and partial pressure of
      O2(p(O2)), the dependence of net CO2 assimilation rate on p(CO2) and irradiance,
      and the influence of p(CO2) and irradiance on the temperature dependence of
      assimilation rate. 

PMID- 24306197
TI  - The phytochrome system in light-grown Zea mays L.
AB  - The phytochrome system is analyzed in light-grown maize (Zea mays L.) plants,
      which were prevented from greening by application of the herbicide SAN 9789. The
      dark kinetics of phytochrome are not different in the first, second or third
      leaf. It is concluded that in light-grown maize plants phytochrome levels are
      regulated by Pr formation and Pfr and Pr destruction, rather than by Pfr->Pr dark
      reversion. Pr undergoes destruction after it has been cycled through Pfr. The
      consequences of this Pr destruction on the phytochrome system are discussed. 

PMID- 24306198
TI  - Measuring potential predictors of burnout and engagement among young veterinary
      professionals; construction of a customised questionnaire (the Vet-DRQ).
AB  - The Job Demands-Resources model (JD-R model) was used as the theoretical basis of
      a tailormade questionnaire to measure the psychosocial work environment and
      personal resources of recently graduated veterinary professionals. According to
      the JD-R model, two broad categories of work characteristics that determine
      employee wellbeing can be distinguished: job demands and job resources. Recently,
      the JD-R model has been expanded by integrating personal resource measures into
      the model. Three semistructured group interviews with veterinarians active in
      different work domains were conducted to identify relevant job demands, job
      resources and personal resources. These demands and resources were organised in
      themes (constructs). For measurement purposes, a set of questions ('a priori
      scale') was selected from the literature for each theme. The full set of a priori
      scales was included in a questionnaire that was administered to 1760 veterinary
      professionals. Exploratory factor analysis and reliability analysis were
      conducted to arrive at the final set of validated scales (final scales). 860
      veterinarians (73 per cent females) participated. The final set of scales
      consisted of seven job demands scales (32 items), nine job resources scales (41
      items), and six personal resources scales (26 items) which were considered to
      represent the most relevant potential predictors of work-related wellbeing in
      this occupational group. The procedure resulted in a tailormade questionnaire:
      the Veterinary Job Demands and Resources Questionnaire (Vet-DRQ). The use of
      valid theory and validated scales enhances opportunities for comparative national
      and international research. 

PMID- 24306199
TI  - Burnout and engagement, and its predictors in young veterinary professionals: the
      influence of gender.
AB  - With the aim to assess levels of burnout and work engagement in junior
      veterinarians and identify predictors of burnout and work engagement in male and
      female veterinarians, 1760 veterinarians who had graduated in The Netherlands
      between 1999 and 2009, received an electronic questionnaire. Veterinarians
      numbering 860 (73 per cent females) participated. Levels of exhaustion, cynicism
      and work engagement were significantly lower compared to the norm group (a random
      sample of the Dutch working population). Male veterinarians were less exhausted
      and more engaged than female veterinarians. Exhaustion decreased over the years.
      Job demands positively related to exhaustion were work-home interference and
      workload. Job resources positively related to work engagement were opportunities
      for professional development and skills discretion (ie, the ability to use and
      develop skills on the job. Personal resources explained more of the variance in
      work engagement of female and male veterinarians (31 per cent and 42 per cent)
      than of the variance in exhaustion (19 per cent and 21 per cent) and cynicism (19
      per cent and 10 per cent). Personal resources positively related to work
      engagement were self-efficacy and proactive behaviour. Relative importance
      analysis revealed differences between men and women in the importance of various
      job demands, job resources and personal resources in explaining burnout and
      engagement in young veterinary professionals. 

PMID- 24306200
TI  - A recurrence-predicting prognostic factor for patients with ovarian clear-cell
      adenocarcinoma at reproductive age.
AB  - OBJECTIVES: We retrospectively analyzed the clinicopathological features and
      evaluated the prognostic indicators of recurrence in 132 patients with clear cell
      adenocarcinoma (CCC) of the ovary at reproductive age. PATIENTS AND METHODS:
      Between 1986 and 2011, as a regional population-based study, clinicopathological
      data on 132 young patients with CCC, collected under the central pathological
      review system, were subjected to uni- and multivariable analyses to evaluate
      recurrence-free survival (RFS). RESULTS: The median age was 40 (27-45) years. The
      median follow-up period for surviving patients was 46.4 months. During the
      observation period, there were 16 recurrences in 87 patients with stage I tumors
      (18.4 %), 8 in 17 with stage II (47.1 %), and 16 in 28 with III-IV (57.1 %).
      Subsequently, 35 patients died of the disease. Those with stage I or II did not
      reach the median RFS. The median RFS of stage III-IV was 21.6 months. When
      analysis was confined to stage I patients, there was no significant difference in
      the RFS of CCC patients between IA and IC(r) (intraoperative capsule rupture) (P
      = 0.7957). In contrast, CCC patients with IC excluding IC(r) [IC(non-r)] showed a
      poorer RFS than those with IC(r) (P < 0.0001). In multivariable analysis confined
      to stage I patients, the substage group was only an independent prognostic factor
      for RFS [IA vs. IC(non-r)] [hazard ratio (HR) = 9.394; 95 % CI, 1.445-61.070; P =
      0.0190]. CONCLUSION: We should keep in mind the greater risk of recurrence in
      patients with stage IC disease or higher, other than those stage IC patients with
      intraoperative rupture.

PMID- 24306201
TI  - Enhancement of spin-crossover cooperativity mediated by lone pair-pi interactions
      and halogen bonding.
AB  - Rational ligand design has allowed the generation of a highly cooperative spin
      transition iron(II) complex, an unprecedented result in the family of (2,2'
      dipyridylamino/s-triazine)-based SCO materials.

PMID- 24306202
TI  - The Allee-type ideal free distribution.
AB  - The ideal free distribution (IFD) in a two-patch environment where individual
      fitness is positively density dependent at low population densities is studied.
      The IFD is defined as an evolutionarily stable strategy of the habitat selection
      game. It is shown that for low and high population densities only one IFD exists,
      but for intermediate population densities there are up to three IFDs. Population
      and distributional dynamics described by the replicator dynamics are studied. It
      is shown that distributional stability (i.e., IFD) does not imply local stability
      of a population equilibrium. Thus distributional stability is not sufficient for
      population stability. Results of this article demonstrate that the Allee effect
      can strongly influence not only population dynamics, but also population
      distribution in space. 

PMID- 24306203
TI  - Gifted adolescents: An analysis of their psychosocial development.
AB  - A model for viewing adolescent psychosocial development is outlined. The model
      assumes that basic changes in adolescents' biological, cognitive, and social
      capacities reciprocally interact with the social settings of the family, peer
      group, and school/work to influence transformations in six areas of psychosocial
      development (attachment, friendship, sexuality, achievement, autonomy, and
      identity). The model is then used as a framework for reviewing literature
      regarding gifted adolescents' psychosocial adjustment. On the whole, the
      literature provides a positive view of the psychosocial adjustment of gifted
      adolescents. While adjustment problems seem to exist in certain areas (e.g.,
      friendship), unequivocal conclusions cannot be drawn because of methodological
      limitations and the narrow scope of existing research. 

PMID- 24306204
TI  - The relationship of observed maternal behavior to questionnaire measures of
      parenting knowledge, attitudes, and emotional state in adolescent mothers.
AB  - Although relationships have been found between maternal psychological
      characteristics and cognitive and emotional outcomes in children, the behaviors
      which may mediate these relationships are seldom examined. This is especially
      true for adolescent mothers, whose children are thought to be at high risk for
      adverse outcomes. In this study, adolescent mothers in two special programs
      completed questionnaires measuring perception of the newborn (Neonatal Perception
      Inventory), knowledge of influences on child development (Infant Caregiving
      Inventory), and emotional state (General Health Questionnaire); they were also
      systematically observed while interacting with their infants in a naturalistic
      situation. Specific maternal behaviors were found to vary with the age of the
      mother and of the baby. Mothers with neutral or negative perceptions of their
      infants touched them less than did mothers with positive perceptions. Degree of
      emotional disturbance was inversely related to the amount of time that the mother
      looked at her infant while in physical contact. 

PMID- 24306205
TI  - Marcia and erikson: The relationships among ego identity status, neuroticism,
      dogmatism, and purpose in life.
AB  - Implicit in James Marcia's writings and in the many studies that have employed
      his measure of ego identity is the assumption that his four ego identity statuses
      are developmentally ordered along a continuum from "being identity diffused" to
      "achieving" an ego identity. In order to assess the validity of this assumption,
      hypotheses were generated and tested concerning the relationship between the
      above ordering and Erikson's writings regarding the role played in the process of
      identity formation by the following three variables: neuroticism, dogmatism, and
      a sense of purpose in life. If one assumes that Erikson's perspective is valid,
      then the results of this study fail to support Marcia's continuum assumption.
      While some of the identity statuses appear to classify persons in a manner
      consistent with Erikson's writings, not one instance of the postulated ordering
      of Marcia's four statuses is observed. It is concluded that Marcia's measure is
      not an adequate operationalization of Erikson's perspective on identity
      formation. 

PMID- 24306206
TI  - Correlates of drug abuse in adolescents: A comparison of families of drug abusers
      with families of nondrug abusers.
AB  - This study was designed to compare drug-abusing adolescents and their families
      with nondrug-abusing adolescents and their families by (1) a comparison of the
      adolescents on measures of self-esteem and perceived parental behavior, (2) a
      comparison of the parents of drug-abusing adolescents with the parents of nondrug
      abusing adolescents on child-rearing attitudes and on distortion in perceived
      parental behavior, and (3) an identification of the salient factors contributing
      to the prediction of drug-use in adolescents. The subjects in this study were 26
      clinical inpatient drug-abusing adolescents and their parents and 26 nondrug
      abusing adolescents and their parents. Testdata consisted of the adolescent's
      self-esteem score on the Self Esteem Inventory (SEI), the adolescent's factor
      score on the Child's Report of Parental Behavior Inventory-Revised (CRPBI-R), and
      the parents' scale score on each of the five factors of the Parent Attitude
      Survey (PAS). Findings indicate that the adolescent's self-esteem and perception
      of parental behavior, the ability of the parents to predict the child's parental
      perceptions, and the professed parental attitudes toward confidence and
      responsibility in child rearing all combine to suggest a set of factors
      differentiating the drug-abusing adolescent from the nondrug-abusing adolescent. 

PMID- 24306207
TI  - Alcohol-related problems and collegiate drinking patterns.
AB  - Six kinds of collegiate problem drinking were examined utilizing a ceptualized
      relationship among the variables of student religious commitment, parental
      attitude toward drinking, neutralization of drinking behavior, drinking before
      college, anticipated ethos of college life, social orientation in college, and
      quantity-frequency of alcohol consumption. Self-administered questionnaires were
      collected from 534 college students and analyzed by path analysis, which
      explained up to 47% of the variation in certain kinds of problem drinking. The
      strongest single predictor of problem drinking was found to be quantity and
      frequency of consumption, but precollege drinking was also important. 

PMID- 24306208
TI  - Genome-wide transcriptional analysis of differentially expressed genes in
      diabetic, healing corneal epithelial cells: hyperglycemia-suppressed TGFbeta3
      expression contributes to the delay of epithelial wound healing in diabetic
      corneas.
AB  - Patients with diabetes mellitus (DM) may develop corneal complications and
      delayed wound healing. The aims of this study are to characterize the molecular
      signatures and biological pathways leading to delayed epithelial wound healing
      and to delineate the involvement of TGFbeta3 therein. Genome-wide cDNA microarray
      analysis revealed 1,888 differentially expressed genes in the healing epithelia
      of normal (NL) versus type 1 DM rat corneas. Gene ontology and enrichment
      analyses indicated TGFbeta signaling as a major altered pathway. Among three
      TGFbeta isoforms, TGF-beta1 and beta3 were upregulated in response to wounding in
      NL corneal epithelial cells (CECs), whereas the latter was greatly suppressed by
      hyperglycemia in rat type 1 and 2 and mouse type 1 DM models. Functional analysis
      indicated that TGF-beta3 contributed to wound healing in NL corneas. Moreover,
      exogenously added TGF-beta3 accelerated epithelial wound closure in type 2 rat
      and type 1 mouse DM corneas via Smad and PI3K-AKT signaling pathways,
      autoregulation, and/or upregulation of Serpine1, a well-known TGFbeta target
      gene. Taken together, our study for the first time provides a comprehensive list
      of genes differentially expressed in the healing CECs of NL versus diabetic
      corneas and suggests the therapeutic potential of TGF-beta3 for treating corneal
      and skin wounds in diabetic patients. 

PMID- 24306209
TI  - Interactions between zinc transporter-8 gene (SLC30A8) and plasma zinc
      concentrations for impaired glucose regulation and type 2 diabetes.
AB  - Although both SLC30A8 rs13266634 single nucleotide polymorphism and plasma zinc
      concentrations have been associated with impaired glucose regulation (IGR) and
      type 2 diabetes (T2D), their interactions for IGR and T2D remain unclear.
      Therefore, to assess zinc-SLC30A8 interactions, we performed a case-control study
      in 1,796 participants: 218 newly diagnosed IGR patients, 785 newly diagnosed T2D
      patients, and 793 individuals with normal glucose tolerance. After adjustment for
      age, sex, BMI, family history of diabetes, and hypertension, the multivariable
      odds ratio (OR) of T2D associated with a 10 ug/dL higher plasma zinc level was
      0.87 (95% CI 0.85-0.90). Meanwhile, the OR of SLC30A8 rs13266634 homozygous
      genotypes CC compared with TT was 1.53 (1.11-2.09) for T2D. Similar associations
      were found in IGR and IGR&T2D groups. Each 10 ug/dL increment of plasma zinc was
      associated with 22% (OR 0.78 [0.72-0.85]) lower odds of T2D in TT genotype
      carriers, 17% (0.83 [0.80-0.87]) lower odds in CT genotype carriers, and 7% (0.93
      [0.90-0.97]) lower odds in CC genotype carriers (P for interaction = 0.01). Our
      study suggested that the C allele of rs13266634 was associated with higher odds
      of T2D, and higher plasma zinc was associated with lower odds. The inverse
      association of plasma zinc concentrations with T2D was modified by SLC30A8
      rs13266634. Further studies are warranted to confirm our findings and clarify the
      mechanisms underlying the interaction between plasma zinc and the SLC30A8 gene in
      relation to T2D. 

PMID- 24306211
TI  - Effects of lipid composition on physicochemical characteristics and cytotoxicity
      of vesicles composed of cationic and anionic dialkyl lipids.
AB  - The behaviors of cat-anionic vesicles composed of dioctadecyldimethylammonium
      bromide (DODAB) and dihexadecyl phosphate (DHP) with varying lipid composition
      were investigated through the measurements of size, zeta potential and
      fluorescence polarization, morphological observations, determination of
      thermotropic phase behavior, cell viability assay, and examination of entrapment
      efficiency and colloid stability. DODAB is miscible with DHP in the bilayer
      domain, which expresses a non-ideal mixing characteristic. The DODAB-rich
      vesicles show a smaller particle size, higher positive zeta potential, lower main
      transition temperature, less angular structure, better storage stability, and
      higher encapsulation efficiency than the DHP-rich ones. Introduction of DODAB
      into DHP vesicles enhances the membrane fluidity in the ripple and liquid
      crystalline phases. The membrane fluidity of mixed DODAB-DHP vesicles with the
      near charge might have a significant effect on the survival of nontransformed
      human skin fibroblast Hs68 cells. The degree of the cytotoxicity of Hs68 cells is
      dominated mainly by the charge nature of DODAB-DHP vesicles with varying lipid
      composition. The results gathered provide necessary information for future
      drug/gene delivery applications. 

PMID- 24306210
TI  - Expression of phosphofructokinase in skeletal muscle is influenced by genetic
      variation and associated with insulin sensitivity.
AB  - Using an integrative approach in which genetic variation, gene expression, and
      clinical phenotypes are assessed in relevant tissues may help functionally
      characterize the contribution of genetics to disease susceptibility. We sought to
      identify genetic variation influencing skeletal muscle gene expression
      (expression quantitative trait loci [eQTLs]) as well as expression associated
      with measures of insulin sensitivity. We investigated associations of 3,799,401
      genetic variants in expression of >7,000 genes from three cohorts (n = 104). We
      identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P <
      1.96 * 10(-5)) and 49 expression-insulin sensitivity phenotype associations
      (i.e., fasting insulin, homeostasis model assessment-insulin resistance, and BMI)
      (FDR <5%; P = 1.34 * 10(-4)). One of these associations, fasting
      insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the
      expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally
      associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and
      overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with
      T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL
      (rs4547172; P = 7.69 * 10(-6)) was nominally associated with glucose uptake,
      glucose oxidation rate, intramuscular triglyceride content, and metabolic
      flexibility (P = 0.016-0.048; n = 178). We explored eQTL results using published
      data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for
      the PFKM eQTL (rs11168327; r(2) = 0.75) was nominally associated with T2D
      (DIAGRAM P = 2.7 * 10(-3)). Taken together, our analysis highlights PFKM as a
      potential regulator of skeletal muscle insulin sensitivity. 

PMID- 24306212
TI  - Factors affecting a dilated ascending aorta in patients with bicuspid aortic
      valve: the relevance of valve anatomy, body size and age.
AB  - PURPOSE: Information regarding the appropriate management of patients with
      moderately dilated ascending aortas is limited. We investigated factors affecting
      ascending aortic dilatation in BAV patients, such as anatomy, body size and age.
      METHODS: We evaluated 130 patients with BAV (age, 59.9 +/- 16.1 years; body
      surface area (BSA), 1.58 +/- 0.20 m(2)) who underwent aortic valve surgery. The
      cusp configuration was determined according to the presence and location of the
      raphe and the cusp direction. The ascending aortic diameter index (AADI) was
      calculated using computed tomography and the BSA. RESULTS: Sixty-four patients
      had A-P-type BAV, while 66 had R-L-type BAV. The mean ascending aorta diameter
      was 42.6 +/- 6.7 mm, and the mean AADI was 27.1 +/- 5.6 mm/m(2). Based on the
      AADI, cusp configuration (R-L-BAV: 28.3 +/- 6.0 mm/m(2) vs. A-P-BAV: 25.8 +/- 4.9
      mm/m(2), P < 0.05), a female gender, age and the presence of aortic stenosis were
      found to be related to ascending aortic dilatation, while the mean ascending
      aortic diameter did not differ between the groups. Among the elderly patients, an
      AADI greater than 28 mm/m(2) was more frequently observed in the R-L-BAV group
      than in the A-P-BAV group. Ascending aortic replacement was required after 10
      years in two patients with R-L-BAV and no patients with A-P-BAV. CONCLUSIONS: The
      relative ascending aortic diameter helped to identify patients with BAV with a
      risk of dilatation, indicating that the use of ascending aortic replacement
      should be considered more frequently in patients with R-L-type BAV, while the
      procedure is avoidable in elderly patients with A-P-type BAV.

PMID- 24306213
TI  - Short- and long-term outcomes for patients with splenic flexure tumours treated
      by left versus extended right colectomy are comparable: a retrospective analysis.
AB  - PURPOSE: To compare the outcomes of colonic splenic flexure tumours treated by
      extended right colectomy versus left colectomy. METHODS: Stage I-III splenic
      flexure tumours, treated either by extended right colectomy or left colectomy
      between 1996 and 2011, were identified in a prospective database, and the short-
      and long-term outcomes compared. The survival analyses were performed using the
      Kaplan-Meier method and adjusted using a Cox-proportional hazard model. RESULTS:
      A total of 30 (44 %) splenic flexure tumours were resected by left colectomy and
      38 (56 %) by right colectomy. Emergency operations were more common (74 versus 20
      %, p < 0.001) in the right colectomy group. In the univariate analysis, the 5
      year overall survival (55 % for right colectomy versus 60 % for left colectomy, p
      = 0.197) and 5-year recurrence-free survival (41 versus 54 %, p = 0.180,
      respectively) showed a trend towards a non-significant survival benefit for left
      colectomy. However, when adjusted for age, gender, ASA classification, tumour
      stage, urgency and year of surgery, this trend disappeared. CONCLUSION: Patients
      undergoing extended right or left colectomy for splenic flexure tumours seemed to
      have comparable short- and long-term outcomes.

PMID- 24306214
TI  - Acute dietary protein intake restriction is associated with changes in myostatin
      expression after a single bout of resistance exercise in healthy young men.
AB  - Skeletal muscle satellite cells (SCs) play an important role in the myogenic
      adaptive response to exercise. It remains to be established whether nutrition
      plays a role in SC activation in response to exercise. In the present study, we
      assessed whether dietary protein alters the SC response to a single bout of
      resistance exercise. Twenty healthy young (aged 21 +/- 2 y) males were randomly
      assigned to consume a 4-d controlled diet that provided either 1.2 g protein ? kg
      body weight(-1) ? d(-1) [normal protein diet (NPD)] or 0.1 g protein ? kg body
      weight(-1) ? d(-1) [low protein diet (LPD)]. On the second day of the controlled
      diet, participants performed a single bout of resistance exercise. Muscle
      biopsies from the vastus lateralis were collected before and after 12, 24, 48,
      and 72 h of post-exercise recovery. SC content and activation status were
      determined using immunohistochemistry. Protein and mRNA expression were
      determined using Western blotting and reverse transcription polymerase chain
      reaction. The number of myostatin + SCs decreased significantly at 12, 24, and 48
      h (range, -14 to -49%; P < 0.05) after exercise cessation, with no differences
      between groups. Although the number of myostatin + SCs returned to baseline in
      the type II fibers on the NPD after 72 h of recovery, the number remained low on
      the LPD. At the 48 and 72 h time points, myostatin protein expression was
      elevated (86 +/- 26% and 88 +/- 29%, respectively) on the NPD (P < 0.05), whereas
      it was reduced at 72 h (-36 +/- 12% compared with baseline) in the LPD group (P <
      0.05). This study demonstrates that dietary protein intake does not modulate the
      post-exercise increase in SC content but modifies myostatin expression in
      skeletal muscle tissue. This trial was registered at clinicaltrials.gov as
      NCT01220037. 

PMID- 24306215
TI  - Indicaxanthin from cactus pear fruit exerts anti-inflammatory effects in
      carrageenin-induced rat pleurisy.
AB  - Nutritional research has shifted recently from alleviating nutrient deficiencies
      to chronic disease prevention. We investigated the activity of indicaxanthin, a
      bioavailable phytochemical of the betalain class from the edible fruit of Opuntia
      ficus-indica (L. Miller) in a rat model of acute inflammation. Rat pleurisy was
      achieved by injection of 0.2 mL of lambda-carrageenin in the pleural cavity, and
      rats were killed 4, 24, and 48 h later; exudates were collected to analyze
      inflammatory parameters, such as nitric oxide (NO), prostaglandin E(2) (PGE(2)),
      interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha); cells
      recruited in pleura were analyzed for cyclooxygenase-2 (COX-2), inducible nitric
      oxide synthase (iNOS) expression, and nuclear factor kappa-light-chain-enhancer
      of activated B cells (NF-kappaB) activation. Indicaxanthin (0.5, 1, or 2
      MUmol/kg), given orally before carrageenin, time- and dose-dependently, reduced
      the exudate volume (up to 70%) and the number of leukocytes recruited in the
      pleural cavity (up to 95%) at 24 h. Pretreatment with indicaxanthin at 2 MUmol/kg
      inhibited the carrageenin-induced release of PGE(2) (91.4%), NO (67.7%), IL-1beta
      (53.6%), and TNF-alpha (71.1%), and caused a decrease of IL-1beta (34.5%), TNF
      alpha (81.6%), iNOS (75.2%), and COX2 (87.7%) mRNA, as well as iNOS (71.9%) and
      COX-2 (65.9%) protein expression, in the recruited leukocytes. Indicaxanthin
      inhibited time- and dose- dependently the activation of NF-kappaB, a key
      transcription factor in the whole inflammatory cascade. A pharmacokinetic study
      with a single 2 MUmol/kg oral administration showed a maximum 0.22 +/- 0.02
      MUmol/L (n = 15) plasma concentration of indicaxanthin, with a half-life of 1.15
      +/- 0.11 h. When considering the high bioavailability of indicaxanthin in humans,
      our findings suggest that this dietary pigment has the potential to improve
      health and prevent inflammation-based disorders.

PMID- 24306216
TI  - The prevalence of low serum vitamin B-12 status in the absence of anemia or
      macrocytosis did not increase among older U.S. adults after mandatory folic acid
      fortification.
AB  - Whether folic acid fortification and supplementation at the population level have
      led to a higher prevalence of vitamin B-12 deficiency in the absence of anemia
      remains to be examined among a nationally representative sample of older U.S.
      adults. We assessed the prevalence of low vitamin B-12 status in the absence of
      anemia or macrocytosis before and after fortification among adults aged >50 y
      using cross-sectional data from the NHANES 1991-1994 (prefortification) and 2001
      2006 (postfortification). We compared the prefortification and postfortification
      prevalence of multiple outcomes, including serum vitamin B-12 deficiency (<148
      pmol/L) and marginal deficiency (148-258 pmol/L) with and without anemia
      (hemoglobin <130 g/L for men, <120 g/L for women) and with and without
      macrocytosis (mean cell volume >100 fL) using multinomial logistic regression,
      adjusting for age, sex, ethnicity, body mass index, C-reactive protein, and
      vitamin B-12 supplement use. Prefortification and postfortification serum vitamin
      B-12 deficiency without anemia [4.0 vs. 3.9%; adjusted prevalence ratio (aPR)
      (95% CI): 0.98 (0.67, 1.44)] or without macrocytosis [4.2 vs. 4.1%; aPR (95% CI):
      0.96 (0.65, 1.43)] remained unchanged. Marginal deficiency without anemia [25.1
      vs. 20.7%; aPR (95% CI): 0.82 (0.72, 0.95)] or without macrocytosis [25.9 vs.
      21.3%; aPR (95% CI): 0.82 (0.72, 0.94)] were both significantly lower after
      fortification. After fortification, higher folic acid intake was associated with
      a lower prevalence of low serum B-12 status in the absence of anemia or
      macrocytosis. Results suggest that the prevalence of low serum B-12 status in the
      absence of anemia or macrocytosis among older U.S. adults did not increase after
      fortification. Thus, at the population level, we found no evidence to support
      concerns that folic acid adversely affected the clinical presentation of vitamin
      B-12 deficiency among older adults. 

PMID- 24306217
TI  - Locally advanced pancreatic cancer: association between prolonged preoperative
      treatment and lymph-node negativity and overall survival.
AB  - IMPORTANCE: Treatment of patients with locally advanced/borderline resectable
      (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. OBJECTIVE:
      To (1) perform a detailed survival analysis of our institution's experience with
      patients with LA/BR PDAC who were downstaged and underwent surgical resection and
      (2) identify prognostic biomarkers that may help to guide a decision for the use
      of adjuvant therapy in this patient subgroup. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective observational study of 49 consecutive patients from a single
      institution during 1992-2011 with American Joint Committee on Cancer stage III
      LA/BR PDAC who were initially unresectable, as determined by staging computed
      tomography and/or surgical exploration, and who were treated and then surgically
      resected. MAIN OUTCOMES AND MEASURES: Clinicopathologic variables and prognostic
      biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by
      univariate and multivariate Cox proportional hazard modeling. RESULTS: All 49
      patients were deemed initially unresectable owing to vascular involvement. After
      completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6
      months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3
      patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were
      lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of
      evaluable patients achieved a complete histopathologic (HP) response. The median
      overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate
      analysis of HP prognostic biomarkers revealed that perineural invasion (hazard
      ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were
      most significant. Lymph-node involvement, as a marker of systemic disease, was
      also significant on univariate analysis (P=.05). Patients with no LN involvement
      had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The
      candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and
      microRNA-21 expression in the stroma (P=.05), also correlated with OS. On
      multivariate Cox proportional hazard modeling of HP and prognostic biomarkers,
      only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). CONCLUSIONS
      AND RELEVANCE: Our approach to patients with LA/BR PDAC, which includes prolonged
      preoperative chemotherapy, is associated with a high incidence of LN-negative
      disease and excellent OS. After surgical resection, HP treatment response,
      perineural invasion, and SMAD4 status should help determine who should receive
      adjuvant therapy in this select subset of patients.

PMID- 24306218
TI  - Larval anatomy of the pterobranch Cephalodiscus gracilis supports secondarily
      derived sessility concordant with molecular phylogenies.
AB  - Pterobranchs have been interpreted as "missing links" combining primitive
      invertebrate features with advanced vertebrate-like characteristics. The first
      detailed morphological description of an ontogenetic stage of a pterobranch,
      based on digital 3D-reconstruction at electron microscopic resolution, reveals a
      triploblastic animal with monociliated epithelia, an extensive coelomic cavity, a
      through gut with an asymmetrically developed gill slit but no signs of planktonic
      specializations, such as ciliated bands. Therefore, this crawling larva supports
      the hypothesis proposed in previous molecular phylogenetic studies that
      pterobranchs could be derived within enteropneusts rather than being "missing
      links".

PMID- 24306219
TI  - Geographical variation in parasitism shapes larval immune function in a
      phytophagous insect.
AB  - Two of the central goals of immunoecology are to understand natural variation in
      the immune system among populations and to identify those selection pressures
      that shape immune traits. Maintenance of the immune system can be costly, and
      both food quality and parasitism selection pressure are factors potentially
      driving immunocompetence. In tritrophic interactions involving phytophagous
      insects, host plants, and natural enemies, the immunocompetence of phytophagous
      insects is constrained by selective forces from both the host plants and the
      natural enemies. Here, we assessed the roles of host plants and natural enemies
      as selective pressures on immune variation among natural populations of Lobesia
      botrana. Our results showed marked geographical variation in immune defenses and
      parasitism among different natural populations. Larval immune functions were
      dependent of the host plant quality and were positively correlated to parasitism,
      suggesting that parasitoids select for greater investment into immunity in moth.
      Furthermore, investment in immune defense was negatively correlated with body
      size, suggesting that it is metabolically expensive. The findings emphasize the
      roles of host plants and parasitoids as selective forces shaping host immune
      functions in natural conditions. We argue that kinds of study are central to
      understanding natural variations in immune functions, and the selective forces
      beyond. 

PMID- 24306220
TI  - Dr Arnold Berliner (1862-1942), physicist and founding editor of
      Naturwissenschaften.

PMID- 24306221
TI  - Association of mean platelet volume with risk of venous thromboembolism and
      mortality in patients with cancer. Results from the Vienna Cancer and Thrombosis
      Study (CATS).
AB  - Venous thromboembolism (VTE) is a frequent complication in cancer patients. Mean
      platelet volume (MPV) has been associated with arterial and venous thrombosis in
      patients without cancer. We analysed MPV in cancer patients and investigated the
      association of MPV with risk of VTE and mortality. MPV was routinely determined
      in the Vienna Cancer and Thrombosis Study, a prospective, observational cohort
      study of patients with newly diagnosed or progressive cancer after remission.
      Study endpoints were occurrence of symptomatic VTE or death during a maximum
      follow-up of two years. Out of 1,544 included patients, 114 (7.4%) developed VTE
      and 573 (37.1%) died during a median observation time of 576 days. High MPV
      >=75th percentile of the study population; >=10.8 fL) was associated with
      decreased risk of VTE compared to MPV below the 75th percentile (HR [95% CI]:
      0.59 [0.37-0.95], p=0.031). In multivariable analysis, including age, sex, cancer
      groups, newly diagnosed vs recurrent disease, platelet count and soluble P
      selectin, this association remained statistically significant (0.65 [0.37-0.98],
      p=0.041). Mortality of patients with MPV (>=75th percentile was significantly
      decreased compared to those with lower MPV (0.72 [0.59-0.88], p=0.001). Two-year
      probability of VTE and overall survival was 5.5% and 64.7% in patients with high
      MPV compared to 9% and 55.7% in those with lower MPV. In conclusion, high MPV is
      associated with decreased VTE risk and improved survival in cancer patients. This
      finding is contrary to results observed in patients without cancer. Further
      studies are needed to confirm our results and elucidate underlying mechanisms. 

PMID- 24306222
TI  - Differential expression of proteins in brain regions of Alzheimer's disease
      patients.
AB  - Alzheimer's disease (AD), a progressive neurodegenerative disorder and the most
      common form of dementia and cognitive impairment is usually characterized by
      neuritic amyloid plaques, cerebrovascular amyloidosis and neurofibrillary
      tangles. In order to find out the pathological protein expression, a quantitative
      proteome analysis of AD hippocampus, substantia nigra and cortex was performed
      and the extent of protein expression variation not only in contrast to age
      matched controls but also among the understudied regions was analyzed. Expression
      alterations of 48 proteins were observed in each region along with significant
      co/contra regulation of malate dehydrogenase, lactate dehydrogenase B chain,
      aconitate hydratase, protein NipSnap homolog 2, actin cytoplasmic 1, creatine
      kinase U-type and glyceraldehyde-3-phosphate dehydrogenase. These differentially
      expressed proteins are mainly involved in energy metabolism, cytoskeleton
      integration, apoptosis and several other potent cellular/molecular processes.
      Interaction association network analysis further confirms the close interacting
      relationship between the co/contra regulated differentially expressed proteins
      among all the three regions. Elucidation of co/contra regulation of
      differentially expressed proteins will be helpful to understand disease
      progression and functional alterations associated with AD.

PMID- 24306225
TI  - Loneliness at adolescence: Correlates, attributions, and coping.
AB  - The present study provides much needed empirical data on the adolescent
      loneliness experience. One hundred adolescents were given measures of loneliness,
      loneliness attributions, coping styles, and personal characteristics. Loneliness
      was positively related to state and trait anxiety, an external locus of control,
      depression, self-consciousness, and social anxiety and negatively related to self
      reported attractiveness, likability, happiness, and life satisfaction. Lonely
      adolescents were also less willing to take social risks. Adolescents most often
      attributed loneliness to boredom and most often coped with loneliness by watching
      TV or listening to music. The implications of these findings for adolescent
      social development are discussed. 

PMID- 24306224
TI  - Diabetic control in children and adolescents: Psychosocial factors and
      therapeutic efficacy.
AB  - Forty-two insulin-dependent latency and adolescent age diabetics were studied
      over a four-month period. Half of the population received a multicomponent
      intervention designed to enhance diabetic regulation. Psychological and
      demographic variables and glycosylation of hemoglobin were correlated in order to
      investigate the interaction between personality factors and metabolic control.
      Number of life event changes predicted initial values of glycohemoglobin, while
      ego development predicted the magnitude of improved diabetic control. 

PMID- 24306226
TI  - The effects of modeling and cognitive induction on the moral reasoning of
      adolescents.
AB  - In this investigation of the effects of modeling and cognitive induction on moral
      reasoning, 87 junior high school students were exposed to moral reasoning,
      characteristic of either one stage above (+1) or one stage below (-1) their
      dominant stage, as determined by pretesting. The presented reasoning was
      attributed to a model of either high, neutral, or low status/relevance to the
      content of the moral dilemmas used. A multiple-choice adaptation of the Kohlberg
      moral development interview was used at pretesting, at intervention/posttesting,
      and at delayed posttesting. Analyses of changes in moral reasoning included
      examination of direct and indirect effects on both an immediate and a delayed
      posttest. Results indicated significant and stable change in moral reasoning
      associated with the developmental stage of the message (+1 produced advances, but
      -1 failed to induce significant regression) and significant temporary change
      associated with the characteristics of the model (high status/relevance models
      had greater influence than did neutral models). It is suggested that future
      research and educational efforts give attention to both the moral stage of the
      intervention and the nature of the source to which it is attributed. 

PMID- 24306227
TI  - Ethnicity and adjustment: A study of the self-image of Anglo-, Greek-, and
      Italian-Australian working class adolescents.
AB  - Two measures of adjustment, the Erikson Psychosocial Stage Inventory and the
      Offer Self-Image Questionnaire, were administered to a sample of 450 working
      class Anglo-, Greek-, and Italian-Australian adolescents in years 9 and 11 of 9
      Melbourne high schools. Anglo- and Greek-Australian adolescents scored similarly
      and significantly higher than Italian-Australians on a number of subscales,
      suggesting that culture conflict may be an influential factor in the adjustment
      of Italian-Australians, but not Greek-Australians. Significant differences
      between the minority groups, in favor of Greek-Australians, were interpreted as
      resulting from the relative differences in institutional support for and press
      toward assimilation of the two groups. 

PMID- 24306228
TI  - Adolescents' grief reactions and self-concept perceptions following sibling
      death: A study of 33 teenagers.
AB  - Thirty-three teenagers were interviewed regarding their grief reactions and self
      concept perceptions following sibling death. The teenagers also completed the
      Offer Self-Image Questionnaire for Adolescents (OSIQ). Grief reactions
      investigated were emotional responses, extent of preoccupations with thoughts of
      the dead sibling, effects on sleeping and eating habits, anniversary reactions,
      hallucinations of the dead sibling, thoughts of suicide, and effects on grades
      and study habits. In addition to OSIQ data, self-concept measures included self
      concept in common contexts, perceptions of personal maturity, lessons learned
      from the sibling's death, relationship with the sibling prior to the death, and
      importance of religious beliefs. Results oft tests on OSIQ standard scores
      indicated that the participants were as adjusted as same-age same-sex norm
      groups. Chi-square analysis and univariateF tests of group differences identified
      emotional responses significantly associated with sex and age characteristics of
      the participants. Statistically significant results emerged regarding effects on
      grades and study habits, perceptions of personal maturity, and increased
      importance of religious beliefs. Discriminant analysis indicated that specific
      emotional responses were influenced by perceptions of family closeness and by
      perceptions of personal communication with family members. Two case descriptions
      highlight some of the typical patterns which the teenagers experienced. 

PMID- 24306229
TI  - The role of the high school professional in identifying and managing adolescent
      suicidal behavior.
AB  - The ongoing contact of adolescents with high school staff may provide an
      opportunity for the early identification and effective management of suicidal
      behavior. In this study, the knowledge, attitude, and experience of 80 high
      school professionals regarding adolescent suicide were assessed through
      semistructured personal interviews. Respondents identified more than 30 signs of
      potential vulnerability - manifestations of depression, verbal and written cues,
      isolation, and self-destructive behaviors. Among predisposing factors, those
      related to alienation within the family were most prominent. Other important risk
      factors were low self-esteem, difficulty in peer relationships, and economic or
      ethnic differences from other students. When suicidal behaviors occurred,
      respondents saw students and staff as attempting to be helpful; families were
      more often viewed as defensive. 

PMID- 24306230
TI  - Effects of HF content in the (FH)(n)F- anion on the formation of ionic plastic
      crystal phases of N-ethyl-N-methylpyrrolidinium and N,N-dimethylpyrrolidinium
      fluorohydrogenate salts.
AB  - Fluorohydrogenate salts based on N-ethyl-N-methylpyrrolidinium (EMPyr(FH)nF) and
      N,N-dimethylpyrrolidinium (DMPyr(FH)nF) cations were synthesized, and the effects
      of the HF content n in EMPyr(FH)nF (1.0 <= n <= 2.3) and DMPyr(FH)nF (1.0 <= n <=
      2.0) on their thermal and structural properties were discussed, focusing on the
      characterization of ionic plastic crystal (IPC) phases. Several solid phases (IPC
      (I) and IPC (II) phases, and crystal phases of EMPyr(FH)1F, EMPyr(FH)2F, and
      EMPyr(FH)3F) are observed in the EMPyr(FH)nF system. The IPC (I) phase has an
      NaCl-type structure and is composed of EMPyr(+) cations and (FH)nF(-) (n = 1, 2,
      and 3) anions randomly occupying the anion positions in the lattice over a wide
      range of n values in (FH)nF(-). The melting point of EMPyr(FH)nF in the range 1.8
      <= n <= 2.3 is maximal at n = 2.0, whereas it increases with a decrease in n in
      the range 1.0 <= n <= 1.2. Furthermore, in the range 1.3 <= n <= 1.7, the solid
      phase is regarded as the IPC phase (IPC (II)), and their melting points are
      nearly constant (260-270 K). In the DMPyr(FH)nF system, the IPC (I') phase and
      crystal phases of DMPyr(FH)1F and DMPyr(FH)2F were observed. Although the IPC
      (I') phase has an NaCl-type structure, similar to the IPC (I) phase of
      EMPyr(FH)nF, it has higher ordering compared to the IPC (I) phase. The melting
      point of DMPyr(FH)nF increases monotonously with decreasing n but disappears in
      the small n region where the salt decomposes below the melting point. 

PMID- 24306231
TI  - Locally measured microstructural parameters are better associated with vertebral
      strength than whole bone density.
AB  - Whole vertebrae areal and volumetric bone mineral density (BMD) measurements are
      not ideal predictors of vertebral fractures. We introduce a technique which
      enables quantification of bone microstructural parameters at precisely defined
      anatomical locations. Results show that local assessment of bone volume fraction
      at the optimal location can substantially improve the prediction of vertebral
      strength. INTRODUCTION: Whole vertebrae areal and volumetric BMD measurements are
      not ideal predictors of vertebral osteoporotic fractures. Recent studies have
      shown that sampling bone microstructural parameters in smaller regions may permit
      better predictions. In such studies, however, the sampling location is described
      only in general anatomical terms. Here, we introduce a technique that enables the
      quantification of bone volume fraction and microstructural parameters at
      precisely defined anatomical locations. Specific goals of this study were to
      investigate at what anatomical location within the vertebrae local bone volume
      fraction best predicts vertebral-body strength, whether this prediction can be
      improved by adding microstructural parameters and to explore if this approach
      could better predict vertebral-body strength than whole bone volume fraction and
      finite element (FE) analyses. METHODS: Eighteen T12 vertebrae were scanned in a
      micro-computed tomography (CT) system and FE meshes were made using a mesh
      morphing tool. For each element, bone microstructural parameters were measured
      and correlated with vertebral compressive strength as measured experimentally.
      Whole bone volume fraction and FE-predicted vertebral strength were also compared
      to the experimental measurements. RESULTS: A significant association between
      local bone volume fraction measured at a specific central region and vertebral
      body strength was found that could explain up to 90% of the variation. When
      including all microstructural parameters in the regression, the predictive value
      of local measurements could be increased to 98%. Whole bone volume fraction could
      explain only 64% and FE analyses 76% of the variation in bone strength.
      CONCLUSIONS: A local assessment of volume fraction at the optimal location can
      substantially improve the prediction of bone strength. Local assessment of other
      microstructural parameters may further improve this prediction but is not
      clinically feasible using current technology.

PMID- 24306232
TI  - Shifting the odds of lifelong mental illness through an understanding of the
      profiles of adolescents and young adults with serious mental health conditions.
AB  - Every day families and mental health providers are called upon to make tough
      decisions in determining the best quality of care for adolescents and young
      adults with serious mental health conditions. This study profiles the behavioral
      and emotional needs and risk behaviors of adolescents and young adults seeking
      mental health services based on assessment of strengths and needs at program
      entry. 

PMID- 24306234
TI  - Antibody-mediated functional control of a dansylated polytheonamide mimic.
AB  - We demonstrate the functional control of a dansylated polytheonamide mimic (2),
      an artificial ion channel-forming cytotoxic peptide, by the external addition of
      a polyclonal anti-dansyl antibody (anti-dansyl IgG). The IgG effectively
      suppressed the ion transport activity and cytotoxicity of 2 in a dose-dependent
      manner.

PMID- 24306233
TI  - CD147/basigin reflects renal dysfunction in patients with acute kidney injury.
AB  - BACKGROUND: Acute tubular necrosis (ATN) describes a form of intrinsic acute
      kidney injury (AKI) that results from persistent hypoperfusion and subsequent
      activation of the immune system. A glycosylated transmembrane protein,
      CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis.
      The present study investigated whether CD147 can reflect pathological features
      and renal dysfunction in patients with AKI. METHODS: Plasma and spot urine
      samples were collected from 24 patients (12 controls and 12 with ATN) who
      underwent renal biopsy between 2008 and 2012. In another study, patients
      undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled
      in 2004. We collected urine and plasma samples from seven patients with AKI and
      33 patients without AKI, respectively. In these experiments, plasma and urinary
      CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured,
      and the former expression in kidneys was examined by immunostaining. RESULTS: In
      biopsy tissues of ATN with severe histological features, CD147 induction was
      strikingly present in inflammatory cells such as macrophages and lymphocytes in
      the injured interstitium, but not in damaged tubules representing atrophy. Both
      plasma and urinary CD147 levels were strikingly increased in ATN patients; both
      values showed greater correlations with renal dysfunction compared to urinary L
      FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147
      values in AKI patients were significantly higher than in non-AKI patients at post
      operative day 1, similar to the profile of urinary L-FABP. CONCLUSION: CD147 was
      prominent in its ability to detect AKI and may allow the start of preemptive
      medication.

PMID- 24306235
TI  - Emprical factors associated with Brainstem auditory evoked potential monitoring
      during microvascular decompression for hemifacial spasm and its correlation to
      hearing loss.
AB  - BACKGROUND: Cranial nerve VIII is at risk during microvascular decompression
      (MVD) for hemifacial spasm (HFS). The primary aim of this study is to evaluate
      the empirical factors associated with brainstem auditory evoked potential
      monitoring and its correlation to post operative hearing loss (HL) after MVD for
      HFS. METHODS: Pre-operative and post-operative audiogram data and BAEP from
      ninety-four patients who underwent MVD for HFS were analyzed. Pure tone
      audiometry (PTA) and Speech Discrimination Score (SDS) were performed on all
      patients before and after surgery. Intraoperative neurophysiological data were
      reviewed independently. HL was assessed using the AAO-HNS classification system
      for non-serviceable hearing loss (Class C/D), defined as PTA >50 dB and/or SDS
      <50% within the speech range of frequencies. RESULTS: Patients with HL had higher
      rates of loss in the amplitude of wave V and prolongation in the interpeak
      latency of peak I-V latency during MVD. Gender, age, side, and MVD duration did
      not increase the risk of HL. There was no correlation between successive number
      of BAEP changes (reflective of the number of surgical attempts) and HL. There was
      no association between the speed of recovery of BAEPs and HL. CONCLUSIONS:
      Patients with new post-operative HL have a faster rate of change in the amplitude
      of wave V and the interpeak I-V latency during intraoperative BAEP monitoring for
      HFS. Our alarm criteria to inform the surgeon about impending nerve injury might
      have to be modified and prospectively tested to prevent rapid change in BAEPs.

PMID- 24306236
TI  - Assessment of active play, inactivity and perceived barriers in an inner city
      neighborhood.
AB  - Avondale, a disadvantaged neighborhood in Cincinnati, lags behind on a number of
      indicators of child well-being. Childhood obesity has become increasingly
      prevalent, as one-third of Avondale's kindergarteners are obese or overweight.
      The study objective was to determine perceptions of the quantity of and obstacles
      to childhood physical activity in the Avondale community. Caregivers of children
      from two elementary schools were surveyed to assess their child's physical
      activity and barriers to being active. Three hundred and forty surveys were
      returned out of 1,047 for a response rate of 32%. On school days, 41% of
      caregivers reported that their children spent more than 2 h watching television,
      playing video games, or spending time on the computer. While over half of
      respondents reported that their children get more than 2 h of physical activity
      on school days, 14% of children were reported to be physically active less than 1
      h per day. Caregivers identified violence, cost of extracurricular activities,
      and lack of organized activities as barriers to their child's physical activity.
      The overwhelming majority of caregivers expressed interest in a program to make
      local playgrounds safer. In conclusion, children in Avondale are not
      participating in enough physical activity and are exposed to more screen time
      than is recommended by the AAP. Safety concerns were identified as a critical
      barrier to address in future advocacy efforts in this community. This project
      represents an important step toward increasing the physical activity of children
      in Avondale and engaging the local community.

PMID- 24306237
TI  - Communication enhancement and best practices for co-managing dual care rural
      Veteran patients by VA and non-VA providers: a survey study.
AB  - Many rural Veteran patients receive healthcare services from both Veterans
      Affairs (VA) and non-VA providers. Effective management of dual care Veteran
      patients to ensure the best clinical outcomes is a VA mission. The previous VA
      studies indicate that coordination between VA and non-VA providers has been
      lacking for dual care management of Veteran patients. In this study, we propose
      that VA proactively shares information with non-VA providers to enhance the
      communication process and identify the best practices to be carried out by both
      VA and non-VA providers for better coordination. Structured questionnaires are
      designed and distributed to VA and non-VA providers to obtain their evaluations
      on the proposed VA proactive information sharing approaches and the best practice
      items for dual care management. The non-VA provider respondents largely support
      the proposed proactive sharing items by VA, with the lowest average score being
      3.96 out of a 5.0 scale on one item. In terms of the best practice items on co
      managing dual care patients, three out of five items are overall rated higher
      than 4.0 from both sides. A pair-wise comparison between VA and non-VA
      perspectives further shows that the difference in average ratings of a proposed
      item could be significant. For such best practice items, the implementations from
      both sides may not be most effective. 

PMID- 24306238
TI  - The mechanism of formation of Cellulose-like microfibrils in a cell-free system
      from Acetobacter xylinum.
AB  - The mechanism of formation of cellulose-like microfibrils by a non-soluble,
      particulate enzyme and uridine diphosphoglucose (UDPG) in a cell-free system from
      Acetobacter xylinum was studied by transmission electron microscopy and X-ray
      diffraction. The suspension of particles to which the enzyme is adsorbed is
      composed of whole, dense ovoids, 50-250 nm long when wet, of fragments of the
      ovoids, and amorphous substance. There is a typical unit membrane around each
      ovoid but initially there is no trace of fibrillar material in the suspension.
      When the suspension of particles is incubated with UDPG, linear wisps of fibrils
      are produced which associate rapidly to form longer and wider threads, especially
      in 0.01 M NaCl. There is no visible attachment of the wisps to the particles.
      After 20 min incubation, threads with the typical morphology of cellulose
      microfibrils are formed that later tend to become entangled in clumps. The
      microfibrils are insoluble in hot, aqueous, alkaline solutions and resistant to
      the action of trypsin, but may be degraded by glusulase. After treatment with 1 M
      NaOH at 100 degrees  C or with cold 18% NaOH they show an X-ray diffraction
      pattern which resembles that of Cellulose II from mercerized, authentic bacterial
      cellulose. Incorporation of radioactive glucose into the insoluble residue is
      enhanced by drying of the cellulose microfibrils before alkaline digestion and
      especially by the addition of a gross excess of carrier cellulose after
      incubation. In this system there is no evidence for participation of linear,
      axial, synthesizing sites on the cell wall of the bacterium or for ordered,
      organized granules in the assembly of the microfibrils. That is, cellulose-like
      microfibrils may be formed in a cell-free system without the action of any of the
      previously suggested cell organelles. In addition, these observations are
      consistent with a previously described notion of a transient, hydrated, nascent,
      bacterial cellulose microfibril. The possibility that cellulose microfibrils of
      green plants may be formed in the same way is considered. 

PMID- 24306239
TI  - Reversal by pressure of seed germination promoted by anesthetics.
AB  - Germination of Panicum capillare L. caryopses induced by solutions of ethanol and
      ethyl ether was prevented by application of pressure >1 MPa during the period of
      exposure to the anesthetic. This effect of pressure indicates that germination is
      correlated with expansion at a site of anesthetic action in a cell membrane. The
      effects of several other anesthetics were measured on germination of P. capillare
      seeds. Ethanol, chloroform, and ethyl ether had the highest activity. Methanol
      and isopropanol were inactive. The effective compounds are thought to distribute
      preferentially to lipid-solution interfaces in cell membranes of the seeds. 

PMID- 24306240
TI  - "Arabidobrassica": A novel plant obtained by protoplast fusion.
AB  - Using somatic hybrid cell lines Arabidopsis thaliana+Brassica campestris,
      obtained by cloning individual protoplast-fusion products as starting material,
      shoots and flowering plants have been regenerated. Cytological, biochemical, and
      morphological analyses indicate that genetic material of both species is present
      in the resultant plants. Shoots and plants obtained from different lines and
      different regeneration events differed morphologically and genetically. Most
      regenerants show morphological abnormalities and unusual organizational patterns.
      Flowering forms have so far been sterile. "Asymmetric" hybrids (i.e., hybrids
      bearing most genetic material of one of the parent species and only few
      chromosomes of the other) were more regular in morphology. The results represent
      the first case of intergeneric-intertribal hybridization of flowering plants. 

PMID- 24306241
TI  - Effects of light and photoperiodic conditions on abscisic acid in leaves and
      roots of Acer pseudoplatanus L.
AB  - Roots of Acer pseudoplatanus seedlings grown in liquid nutrient medium contained
      much lower levels of both free and bound abscisic acid than did leaves. The
      levels of free abscisic acid were similar in young expanding and of mature
      leaves, but lower in older senscing leaves. Growing plants under long days or
      short days did not influence the levels of free and bound abscisic acid in
      leaves. However, under both long days and short days, levels of bound abscisic
      acid were lower at the end of the dark period than 8 h later during the light
      period. Phaseic acid was also detected during the light period but never at the
      end of the dark period. 

PMID- 24306242
TI  - Preparation of intact chloroplasts by chemically induced lysis of the green alga
      Dunaliella marina.
AB  - A method for the isolation in high yield of intact chloroplasts from the
      unicellular green alga Dunaliella marina (Volvocales) is described. This
      procedure uses chemically induced lysis of cells with the polycationic
      macromolecules, DEAE-dextran (M=500,000) or poly-D,L-lysine (M=30,000-70,000).
      Reaction conditions were optimized with respect to obtaining a high yield of
      intact chloroplasts, after isopycnic centrifugation in a linear sucrose density
      gradient, by varying the concentration of polycation and the temperature and pH
      of incubation. Broken chloroplasts devoid of the stromal marker enzymes
      fructosebisphosphate phosphatase and ribulosebisphosphate carboxylase, but
      containing mitochondrial (fumarase) and microbody (catalase) contamination, were
      banded at a bouyant density of 1.18 g cm(-3). Intact chloroplasts, as indicated
      by their retention of alkaline fructosebisphosphate phosphatase and
      ribulosebisphosphate carboxylase, were found in 30% yield (chlorophyll in intact
      cells, 100%) at an equilibrium density of 1.24 g cm(-3). Contamination by
      cytoplasmic material (pyruvate kinase), mitochondria, and microbodies was less
      than 8% each. 

PMID- 24306243
TI  - Identification and subcellular localization of starch-metabolizing enzymes in the
      green alga Dunaliella marina.
AB  - Enzymes of starch synthesis and degradation were identified in crude extracts of
      the unicellular green alga Dunaliella marina (Volvocales). By polyacrylamide gel
      electrophoresis and specific staining for enzyme activities, 4 multiple forms of
      starch synthase, 2 amylases, and at least 2 forms of alpha-glucan phosphorylase
      were visible. Using specific alpha-glucans incorporated into the gel before
      electrophoresis we have tentatively correlated alpha-amylase and beta-amylase
      with both hydrolytic activities. The activities of alpha-glucan phosphorylase and
      amylase(s) were measured quantitatively in crude extracts, and the concomitant
      action of alpha-glucan phosphorylase and amylase(s) was found to account for the
      fastest rate of starch mobilization observed in vivo. Isolated chloroplasts
      retained both typical plastid marker enzymes and ADPglucose pyrophosphorylase,
      starch synthase, amylase(s), and alpha-glucan phosphorylase to a similar
      percentage. Gel electrophoretic analysis followed by staining for enzyme activity
      of a stromal fraction resulted in a pattern of multiple forms of starch
      metabolizing enzymes analogous to that found in a crude extract. We interpret the
      combined data as indicating the exclusive location in vivo of starch-metabolizing
      enzymes in chloroplasts of D. marina. 

PMID- 24306244
TI  - The regulation of the energy-dependent phosphate uptake by the blue-green alga
      Anacystis nidulans.
AB  - Investigations of the energy-dependent accumulation of orthophosphate by the blue
      green alga Anacystis nidulans have established: 1. The transport through the cell
      membrane is the rate-limiting step in the incorporation of phosphate.-2. This
      transport is facilitated by a "carrier" that can be activated by Ca(2+) and
      Mg(2+) and inhibited by EDTA.-3. The activation of the carrier in the light is
      associated with changes of the cytoplasmic Mg(2+) content.-4. Intracellular
      phosphate is shown to be present in bound form.-5. The energy-dependent
      accumulation of orthophosphate within the cell depends strictly on the
      cytoplasmic pH and not on the energy conversion at the thylakoid membrane which
      is responsible for the energy supply. The cytoplasmic pH is different in the
      light, in the dark, and in the presence of the uncoupler carbonyl cyanide m
      chlorophenylhydrazone (CCCP). Orthophosphate accumulation can most readily be
      explained in terms of a pH dependent precipitation into a complex with bivalent
      cations rather than by an active transport against a concentration gradient. 

PMID- 24306245
TI  - Phloem loading in Vicia faba leaves: Effect of N-ethylmaleimide and
      parachloromercuribenzenesulfonic acid on H(+) extrusion, K (+) and sucrose
      uptake.
AB  - The effects of a penetrating (NEM) and a non-penetrating (PCMBS) sulfhydryl
      specific reagent on proton extrusion, (86)Rb and [U-(14)C]sucrose uptake by Vicia
      faba leaves have been studied. Proton extrusion was strongly or completely
      inhibited by 0.1 mM NEM. (86)Rb and [U-(14)C]sucrose uptake were markedly reduced
      by NEM concentrations equal to or higher than 0.5 mM. Under our experimental
      conditions, PCMBS (1 mM) exerted a strong inhibition on [(14)C]sucrose uptake but
      did not inhibit proton extrusion and (86)Rb uptake. The sensitivity of phloem
      loading to PCMBS is thought to be a consequence of sugar-carrier blockage and not
      of inhibition of the proton pump. 

PMID- 24306246
TI  - Mobilization of proline in the starchy endosperm of germinating barley grain.
AB  - In germinating grains of barley, Hordeum vulgare L. cv. Himalaya, free proline
      accumulated in the starchy endosperm during the period of rapid mobilization of
      reserve proteins. When starchy endosperms were separated from germinating grains
      and homogenized in a dilute buffer of pH 5 (the pH of the starchy endosperm), the
      liberation of proline continued in these suspensions. The process was completely
      inhibited by diisopropylfluorophosphate, indicating that it was totally dependent
      on serine carboxy-peptidases. The carboxypeptidases present in the starchy
      endosperms of germinating grains were fractionated by chromatography on DEAE
      cellulose. Four peaks were obtained, all with different activity spectra on the
      seven carbobenzoxydipeptides (Z-dipeptides) tested. Two of the peaks corresponded
      to previously known barley carboxypeptidases; these as well as a third peak
      hydrolyzed substrates of the types Z-X-Y and Z-X-Pro (X and Y denote any amino
      acid residue except proline). The fourth peak corresponded to a proline
      carboxypeptidase specific for substrates of the Z-Pro-X type. Apparently, in the
      hydrolysis of longer proline-containing peptides there must be sequential
      cooperation between the two carboxypeptidase types. The carboxypeptidases in
      extracts of starchy endosperms also liberated proline from the peptides Ala-Ala
      Ala-Pro and Ala-Ala-Pro while Ala-Pro and Pro-Ala were not attacked. The
      dipeptides, however, were rapidly hydrolyzed around pH 7 by extracts prepared
      from the scutella of germinating grains. It is concluded that one part of the
      proline residues of the reserve proteins is liberated in situ in the starchy
      endosperm through the combined action of acid proteinases and carboxypeptidases,
      while another part is taken up in the form of small peptides by the scutellum,
      where proline is liberated by amino- and/or dipeptidases in some "neutral
      compartment". 

PMID- 24306247
TI  - Radioimmunoassays for trans-zeatin and related cytokinins.
AB  - Radioimmunoassays for the quantitation of trans-zeatin and related cytokinins
      have been developed. Antisera produced against bovine serum albumin conjugates of
      trans-zeatinriboside have a high affinity (Ka=2.4.10(-11) M) for zeatinriboside
      and for zeatin, but show a negligible cross reaction to isopentenyladenosine
      (0.1%) and cis-zeatinriboside (0.4%), only a slight cross reaction to
      dihydrozeatin (1.7%), and no cross reaction at all to other purines, such as
      adenosine and related, compounds, was observed. The assays are sensitive and
      measuring ranges extend from 0.06-30 pmol (0.02-10 ng) of zeatinriboside. This
      has been achieved by employing as tracers immunoreactive zeatin derivatives with
      high-specific activity, (tritiated zeatinriboside-dialcohol: 8.37.10(11) Bq mmol(
      1) and zeatinribosyl-[(125)I]tyramine: ca. 1.9.10(13) Bq mmol(-1). The detection
      limit is 40 fmol (15pg) for the assay employing the tritiated tracer, and assay
      reproducibility is high (variation coefficients of triplicates less than 5%).
      Several hundred assays can be completed in one day, and, due to the high
      specificity of this assay, crude extracts may be used for analysis. The course of
      zeatin levels in developing fruits of Lycopersicon esculentum cv. Moneymaker is
      given. 

PMID- 24306248
TI  - Capacity for RNA synthesis in 70S ribosome-deficient plastids of heat-bleached
      rye leaves.
AB  - In the leaves of rye seedlings (Secale cereale L.) grown at an elevated
      temperature of 32 degrees C the formation of plastidic 70S ribosomes is
      specifically prevented. The resulting plastid ribosome-deficient leaves, which
      are chlorotic in light, represent a system for the identification of translation
      products of the 80S ribosomes among the chloroplastic proteins. Searching for the
      primary heat-sensitive event causing the 70S ribosome-deficiency, the
      thermostability of the chloroplastic capacity for RNA synthesis was investigated.
      The RNA polymerase activity of isolated normal chloroplasts from 22 degrees 
      grown rye leaves was not inactivated in vitro at temperatures between 30 degrees 
      and 40 degrees C. The ribosome-deficient plastids purified from bleached 32
      degrees -grown leaf parts contained significant RNA polymerase activity which
      was, however, lower than in functional chloroplasts. After application of
      [(3)H]uridine to intact leaf tissues [(3)H]uridine incorporation was found in
      ribosome-deficient plastids of 32 degrees C-grown leaves. The amount of
      incorporation was similar to that in the control chloroplasts from 22 degrees C
      grown leaves. According to these results, it is unlikely that the non-permissive
      temperature (32 degrees C) causes a general inactivation of the chloroplastic RNA
      synthesis in rye leaves. 

PMID- 24306249
TI  - The role of monovalent cations for photosynthesis of isolated intact
      chloroplasts.
AB  - The role of monovalent cations in the photosynthesis of isolated intact spinach
      chloroplasts was investigated. When intact chloroplasts were assayed in a medium
      containing only low concentrations of mono- and divalent cations (about 3 mval l(
      1)), CO2-fixation was strongly inhibited although the intactness of chloroplasts
      remained unchanged. Addition of K(+), Rb(+), or Na(+) (50-100 mM) fully restored
      photosynthesis. Both the degree of inhibition and restoration varied with the
      plant material and the storage time of the chloroplasts in "low-salt" medium. In
      most experiments the various monovalent cations showed a different effectiveness
      in restoring photosynthesis of low-salt chloroplasts (K(+)>Rb(+)>Na(+)). Of the
      divalent cations tested, Mg(2+) also restored photosynthesis, but to a lesser
      extent than the monovalent cations.In contrast to CO2-fixation, reduction of 3
      phosphoglycerate was not ihibited under low-salt conditions. In the dark, CO2
      fixation of lysed chloroplasts supplied with ATP, NADPH, and 3-phosphoglycerate
      strictly required the presence of Mg(2+) but was independent of monovalent
      cations. This finding excludes a direct inactivation of Calvin cycle enzymes as a
      possible basis for the inhibition of photosynthesis under low-salt
      conditions.Light-induced alkalization of the stroma and an increase in the
      concentration of freely exchangeable Mg(2+) in the stroma, which can be observed
      in normal chloroplasts, did not occur under low-salt conditions but were strongly
      enhanced after addition of monovalent cations (50-100 mM) or Mg(2+) (20-50
      mM).The relevance of a light-triggered K(+)/H(+) exchange at the chloroplast
      envelope is discussed with regard to the light-induced increase in the pH and the
      Mg(2+) concentration in the stroma, which are thought to be obligatory for light
      activation of Calvincycle enzymes. 

PMID- 24306250
TI  - Qualitative and quantitative aspects of betalains biosynthesis in Amaranthus
      caudatus L. var. pendula seedlings.
AB  - Seedlings of Amaranthus caudatus L. var. Pendula were used to study the influence
      of several treatment: white light, 3,4-dihydroxyphenylalanine (DOPA), kinetin,
      gibberellic acid (GA3) on betalains biosynthesis. The pigments, betacyanins and
      betaxanthins, were separated using a Sephadex G-15 column chromatography.
      Qualitative as well as quantitative differences were observed according to the
      treatments applied.The amaranthin biosynthesis seemed to be favored in the
      absence of DOPA. Under the combined effect of kinetin and white light a small
      quantity of betanin was also synthesized. Adding exogenous DOPA led to a more
      diversified production which included betacyanins (amaranthin and betanin),
      betaxanthins (vulgaxanthin and miraxanthin), and even dopachrome. As a general
      rule, kinetin activated the betalains biosynthesis whereas GA3 inhibited it. The
      stimulating effect of white light was always much greater than that of kinetin. 

PMID- 24306251
TI  - Reorganization of cortical microtubules and cellulose deposition during leaf
      formation in Graptopetalum paraguayense.
AB  - In the "regeneration" of a shoot from a leaf of the succulent, Graptopetalum
      paraguayense E. Walther the first new organs are leaf primordia. The original
      arrangement of cellulose microfibrils and of microtubules (MTs) in the epidermis
      of the leaf-forming site is one of parallel, straight lines. In the new
      primordium both structures still have a congruent arrangement but it is roughly
      in the form of concentric circles that surround the new cylindrical organ. The
      regions which undergo the greatest shift in orientation (90 degrees ) were
      studied in detail. Departures from the original cellulose alignment are detected
      in changes in the polarized-light image. Departures from the original cortical MT
      arrangement are detected using electron microscopy. The over-all reorganization
      of the MT pattern is followed by the tally of MT profiles, the various regions
      being studied in two perpendicular planes of section. This corrects for the
      difference in efficiency in counting transverse versus longitudinal profiles of
      MTs. Reorientation takes place sporadically, cell by cell, for both the cellulose
      microfibrils and the MTs, indicating a coordinated reorientation of the two
      structures. That MTs and cellulose microfibrils reorient jointly in individual
      cells was shown by reconstruction of the arrays of cortical MTs in paradermal
      sections of individual cells whose recent change in the orientation of cellulose
      deposition had been detected with polarized light. Closeness of the two
      alignments was also indicated by images where the MT and microfibril alignments
      co-varied within a single cell. The change-over in alignment of the MTs appears
      to involve stages where arrays of contrasting orientation co-exist to give a
      criss-cross image. During this critical reorganization, the frequency of the MTs
      is high. It falls during subsequent enlargement of the organ. It was found that
      the rearrangement of the cortical MTs to approximate a series of concentric
      circles on the residual meristem occurred before the emergence of leaf primordia.
      Through their apparent influence on microfibril alignments, the changes in MT
      disposition, described here, have the potential to generate major biophysical
      changes that accompany organogenesis. 

PMID- 24306252
TI  - The effect of light on the production of ethylene from 1-aminocyclopropane-1
      carboxylic acid by leaves.
AB  - White light inhibits the conversion of 1-amino-cyclopropane-1-carboxylic acid
      (ACC) in discs of green leaves of tobacco (Nicotiana tabacum L.) and segments of
      oat (Avena sativa L.) leaves by from 60 to 90%. Etiolated oat leaves do not show
      this effect. The general nature of the effect is shown by its presence in both a
      mono- and a dicotyledon. Since the leaves have been grown and pre-incubated in
      light, yet can produce from 2 to 9 times as much ethylene in the dark as in the
      light, it follows that the light inhibition is fully reversible. The inhibition
      by light is about equal to that exerted in the dark by CoCl2; it can be partly
      reversed by dithiothreitol and completely by mercaptoethanol. Thus the light is
      probably acting, via the photosynthetic system, on the SH group(s) of the enzyme
      system converting ACC to ethylene. 

PMID- 24306253
TI  - Increase in anthocyanin yield from wild-carrot cell cultures by a selection
      system based on cell-aggregate size.
AB  - Wild-carrot (Daucus carota L.) cell cultures were screened to yield small (less
      than 63 MUm) or large (greater than 170 MUm) cell aggregates which were then
      subcultured. Cultures of the small-size class had a higher, those of the large
      size class a lower anthocyanin yield than the unscreened culture. This
      relationship became accentuated with an increasing number of passages with
      screening prior to subculture. At the end of six months (12 passages), the
      pigment yield of the small-size class was triple that of the unscreened cells.
      Following this selection period, the tendency of the small-size fraction to
      increase in clump size when subcultured without screening was much less than that
      of freshly isolated cell aggregates of the same size. These observations may be
      explainable on the basis of a differential distribution of cytokinin between
      aggregates of different sizes. High levels of cytokinin inhibit anthocyanin
      accumulation and inhibit cell separation; these effects result in large cell
      aggregates having low levels of anthocyanin. In support of this hypothesis, it is
      shown that addition of kinetin to cultures of small cell aggregates causes an
      increase in the size of cell aggregates and a parallel decrease in anthocyanin
      yield. 

PMID- 24306254
TI  - Correlation between the nicotine content of tobacco plants and callus cultures.
AB  - Callus cultures of two low-alkaloid lines of Nicotiana tabacum L. had
      considerably lower nicotine contents than cultures from the respective
      highalkaloid cultivars which were isogenic except for the two loci for alkaloid
      accumulation. Thus, there was a strong correlation between the nicotine content
      of callus cultures and the plants from which they were derived. 

PMID- 24306255
TI  - Role of mitochondrial glutamate dehydrogenase in the reassimilation of ammonia
      produced by glycine serine transformation.
AB  - The ability of isolated pea-shoot mitochondria conditioned to incorporate ammonia
      into glutamate to reassimilate endogenously produced ammonia from glycine
      transformation was investigated. In the presence of 1 mM to 20 mM glycine less
      than 15% of the ammonia liberated was found to be incorporated into glutamate.
      Thus, a prominent role of mitochondrial glutamate dehydrogenase in the
      reassimilation of intramitochondrially produced ammonia can be excluded. 

PMID- 24306256
TI  - Homoleptic aminophenolates of Zn, Mg and Ca. Synthesis, structure, DFT studies
      and polymerization activity in ROP of lactides.
AB  - The reaction of MgBu2, ZnEt2 or Ca(O(i)Pr)2 with 2 eq. of three-coordinating N
      [methyl(2-hydroxy-3,5-dimethylphenyl)]-N-methyl-N-methyl-1,3-oxolaneamine (mpoa
      H) or N-[methyl(2-hydroxy-3,5-di-tert-butylphenyl)]-N-methyl-N-methyl-1,3
      oxolaneamine (tbpoa-H) gave neutral, monomeric [Mg(mpoa)2], [Zn(mpoa)2],
      [Zn(tbpoa)2], and [Ca(tbpoa)2] as white powders in 58-90% yields. The resulting
      aminophenolates were characterized in solution by NMR showing, in the case of
      [Zn(tbpoa)2], interesting dynamics. [Zn(tbpoa)2] and [Ca(tbpoa)2] were
      characterized by X-ray crystallography to show the Zn atom to be pseudo
      octahedrally coordinated and the Ca atom in six-coordination mode. The new
      homoleptic complexes were tested in the polymerization of lactide with an
      external alcohol to reveal stable behaviour (during the polymerization process)
      only in the case of [Zn(tbpoa)2]. The high activity of the catalyst was
      correlated with a ligand flexibility that was further supported by theoretical
      studies. 

PMID- 24306257
TI  - Personalizing breast cancer staging by the inclusion of ER, PR, and HER2.
AB  - IMPORTANCE: Nonanatomic factors, such as histologic grade and biomarkers, can
      guide breast cancer management but are not included in the current TNM staging
      system. OBJECTIVE: To use as an example the triple-negative phenotype (TNP)
      defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and
      human epidermal growth factor 2 (HER2) to examine whether such inclusion improves
      the prognostic accuracy of TNM staging for breast cancer. DESIGN, SETTING, AND
      PARTICIPANTS: Women diagnosed with primary invasive ductal breast cancer from
      January 1, 1991, through December 31, 2008, were identified from a prospective
      institutional database. Excluded were patients who received neoadjuvant therapy,
      those whose staging information was incomplete, or those whose tumor lacked ER,
      PR, and HER2 data. Breast cancers were categorized by TNM stage and by the
      presence or absence of TNP. MAIN OUTCOMES AND MEASURES: Overall survival at 5
      years. RESULTS: Database review identified 1842 consecutive eligible patients
      with breast cancer. When patients were stratified by TNM stage, overall survival
      curves for those with TNP breast cancer matched those for patients whose non-TNP
      breast cancer was 1 TNM stage higher. Multivariable analysis showed that TNP
      status was a powerful prognostic variable, and the likelihood ratio test revealed
      that the prognostic accuracy of the TNM staging system that incorporated TNP was
      superior to the current TNM staging system (P< .001). A TNM staging system that
      incorporated TNP reduced early-stage compression by 15%. CONCLUSIONS AND
      RELEVANCE: The internationally recognized and easily reproducible examination of
      ER, PR, and HER2 status exemplifies how nonanatomic factors can improve the
      prognostic accuracy of breast cancer staging.

PMID- 24306258
TI  - [Work rehabilitation in people with severe mental illnesses].
AB  - Work and employment are basic human rights. Work therapy has a long-standing
      tradition in mental health care. Integrating people with severe mental illness
      into jobs has always been considered indispensable. Germany has a good legal
      framework for work rehabilitation and there is solid evidence of effectiveness
      for a range of interventions. International models of work integration have not
      been implemented to a sufficient degree and this may be one of the reasons for
      limited success in work rehabilitation for people with mental illnesses. The need
      for work rehabilitation measures and the available evidence are outlined. Social
      legislation, conceptual and organizational aspects of rehabilitation are
      described. International comparisons suggest that the care system will have to
      integrate prevention, curative treatment, rehabilitation and long-term care in a
      better way. 

PMID- 24306259
TI  - Some thoughts on normal adolescents who lost a parent by death.
AB  - This study is an attempt to determine the effects of the loss of a parent by
      death in childhood on adolescents who were not part of a clinic population. In a
      longitudinal study of 350 normal adolescents by Peterson and Offer, 7 teenagers
      had lost a parent between the ages of 7 and 10 1/2. These 7 research protocols
      were reviewed at ages 12 and 13. Almost all of these youngsters were intensely
      involved with siblings and peers as a way to help them adapt to their loss. At
      least one-half of this group of normal adolescents had some type of therapeutic
      contact since the parent's death. At age 12 these youngsters appeared to be
      coping with their loss by extracting from their environment the necessary help
      and support. At age 13 they were still coping, but their adaptation appeared more
      precarious. 

PMID- 24306260
TI  - Adolescent conceptions of the homeland: A cross-cultural study.
AB  - Irish (135) and United States (123) subjects, aged from 8 to 17 years, wrote
      essays on their respective homelands. A content analysis revealed that American
      subjects, as they grow older, identify the homeland increasingly with its
      political ideals, while Irish subjects identify theirs with certain psychological
      ideals which they associate with the rural culture and landscape. Irish essays
      tended to be longer and more varied, and they showed a higher level of affective
      development. Profiles of the homeland on 7 semantic differential scales showed
      the break-up of a halo effect in the Irish sample. Adolescents in both countries
      showed a transition from concrete to abstract topics with age. The implications
      of these findings for research on the adolescent self-image are discussed. 

PMID- 24306261
TI  - Social competence during adolescence: Social sensitivity, locus of control,
      empathy, and peer popularity.
AB  - In male and female adolescents aged 14, 15, 17, and 18 years of age, the
      predictive relationship between social competency and peer relations and age
      differences in social competence were studied. Based upon a social deficit
      hypothesis, linear age differences were observed in social knowledge, locus of
      control, and a trend in empathy. Some sex differences were found, but no sex by
      age interactions were observed. The predicted relationship between social
      competency and peer popularity was supported, but was different according to sex
      of the adolescent. 

PMID- 24306262
TI  - Physiological concentrations of unconjugated bilirubin prevent oxidative stress
      induced hepatocanalicular dysfunction and cholestasis.
AB  - Bilirubin is an endogenous antioxidant with cytoprotective properties, and
      several studies highlight its potential in the treatment of pro-oxidant diseases.
      We demonstrated that oxidative stress (OS), a key feature in most hepatopathies,
      induces cholestasis by actin cytoskeleton disarrangement and further endocytic
      internalization of key canalicular transporters, such as the bile salt export
      pump (Bsep) and the multidrug resistance-associated protein 2 (Mrp2) . Here, we
      evaluated the capability of physiological concentrations of unconjugated
      bilirubin (UB) to limit OS and the impairment in biliary secretory function
      induced by the model pro-oxidant agent, tert-butylhydroperoxide (tBuOOH). UB
      fully prevented the formation of reactive oxygen species and membrane lipid
      peroxidation induced by tBuOOH in isolated rat hepatocytes. In the isolated rat
      hepatocyte couplet model, UB (17.1 MUM) prevented the endocytic internalization
      of Bsep and Mrp2 and the impairment in their secretory function induced by
      tBuOOH. UB also prevented actin disarrangement, as evaluated by both plasma
      membrane bleb formation and actin fluorescent staining. Finally, UB prevented
      tBuOOH-induced cPKC activation. Experiments in isolated perfused rat livers
      showed that UB prevents the increase in oxidized glutathione biliary excretion
      and the drop in bile flow and the biliary excretion of specific Bsep and Mrp2
      substrates. We conclude that physiological concentrations of UB are sufficient to
      prevent the biliary secretory failure induced by OS, by counteracting actin
      disarrangement and the consequent internalization of canalicular transporters
      relevant to normal bile formation. This reveals an important role for UB in
      preserving biliary secretory function under OS conditions.

PMID- 24306263
TI  - Emergency medicine resident well-being: stress and satisfaction.
AB  - BACKGROUND: Emergency medicine (EM) residents are exposed to many work-related
      stressors, which affect them both physically and emotionally. It is unknown,
      however, how EM residents perceive the effect of these stressors on their well
      being and how often they use unhealthy coping mechanisms to manage stress. AIMS:
      To evaluate EM residents' perceptions of stressors related to their overall well
      being and the prevalence of various coping mechanisms. METHODS: An online survey
      instrument was developed to gauge resident stress, satisfaction with current
      lifestyle, stress coping mechanisms and demographics. A stratified random sample
      of EM residents from three postgraduate years (PGY-I, PGY-II and PGY-III) was
      obtained. Descriptive statistics and one-way analysis of variance were used to
      compare residents across PGY level. RESULTS: There were 120 potential
      participants in each of the three PGYs. The overall response rate was 30% (109)
      with mean age of 30 and 61% were male. On a 0-4 scale (0 = completely
      dissatisfied), respondents in PGY-I reported significantly less satisfaction with
      lifestyle than those in PGY-II and III (mean rating: 1.29, 1.66 and 1.70,
      respectively; P < 0.001). There were no significant differences in mean ratings
      between PGYs on each of the other stress categories: work relationships (1.37),
      work environment (1.10) and response to patients (1.08). Residents reported
      exercise (94%), hobbies (89%) and use of alcohol (71%) as coping methods.
      CONCLUSIONS: Residents reported low satisfaction with current lifestyle. This
      dissatisfaction was unrelated to perceived work-related stress. Some undesirable
      coping methods were prevalent, suggesting that training programs could focus on
      promotion of healthy group activities.

PMID- 24306264
TI  - An effective mesoscopic model of double-stranded DNA.
AB  - Watson and Crick's epochal presentation of the double helix structure in 1953 has
      paved the way to intense exploration of DNA's vital functions in cells. Also,
      recent advances of single molecule techniques have made it possible to probe
      structures and mechanics of constrained DNA at length scales ranging from
      nanometers to microns. There have been a number of atomistic scale quantum
      chemical calculations or molecular level simulations, but they are too
      computationally demanding or analytically unfeasible to describe the DNA
      conformation and mechanics at mesoscopic levels. At micron scales, on the other
      hand, the wormlike chain model has been very instrumental in describing
      analytically the DNA mechanics but lacks certain molecular details that are
      essential in describing the hybridization, nano-scale confinement, and local
      denaturation. To fill this fundamental gap, we present a workable and predictive
      mesoscopic model of double-stranded DNA where the nucleotides beads constitute
      the basic degrees of freedom. With the inter-strand stacking given by an
      interaction between diagonally opposed monomers, the model explains with
      analytical simplicity the helix formation and produces a generalized wormlike
      chain model with the concomitant large bending modulus given in terms of the
      helical structure and stiffness. It also explains how the helical conformation
      undergoes overstretch transition to the ladder-like conformation at a force
      plateau, in agreement with the experiment. 

PMID- 24306265
TI  - Nucleotide sensing with a perylene-based molecular receptor via amplified
      fluorescence quenching.
AB  - A competitive fluorescence assay of perylene-based molecular receptors has been
      established, and selective detection of UTP is achieved through improved
      aggregation arising from the specific interaction of perylene-tethered
      guanidinium with uridine and phosphate groups in UTP. 

PMID- 24306266
TI  - Attitudes of people with osteoarthritis towards their conservative management: a
      systematic review and meta-ethnography.
AB  - This paper determines the perceptions of people diagnosed with osteoarthritis
      towards their conservative management strategies. A systematic review of the
      published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane
      Clinical Trials Registry, PubMed) and unpublished/trial registry databases (WHO
      International Clinical Trials Registry Platform, Current Controlled Trials, the
      United States National Institute of Health Trials Registry, NIHR Clinical
      Research Portfolio Database) searched from their inception to July 2013. Eligible
      studies included those which presented the attitudes or perceptions of people
      with osteoarthritis towards non-operative management strategies. Study quality
      was appraised using the CASP and the Gough's weight of evidence appraisal tools.
      Data were analysed through a meta-ethnography approach. Thirty-three studies
      including 1,314 people with osteoarthritis were sampled; the majority diagnosed
      with knee osteoarthritis. The overarching themes indicated people with
      osteoarthritis delay their diagnosis, opting for self-management and informal
      information gathering. This informal rather than health professional-led guidance
      is sought and maintained as an important resource throughout the care of this
      population and is valued. Diagnosis is sought at a 'critical point'. Healthcare
      interventions largely provided are poorly perceived. The period of subsequent
      self-management is an expectation before the inevitable requirement for joint
      replacement. There remains uncertainty regarding when this is required, but the
      expected failure of conservative treatment to manage pain and symptoms is common.
      In conclusion, patients should be enthused towards the principles of self
      management and clinicians should not trivialise osteoarthritis. This may provide
      a more valuable perception of non-operative management to promote its adoption
      and adherence in managing osteoarthritis. 

PMID- 24306267
TI  - New evidence for roles of growth arrest-specific protein 6 (Gas6) in systemic
      lupus erythematosus.

PMID- 24306268
TI  - A meta-analysis of the relationship between aspartic acid (D)-repeat
      polymorphisms in asporin and osteoarthritis susceptibility.
AB  - Our aim was to determine whether asporin (ASPN) D-repeat polymorphisms are
      associated with susceptibility to osteoarthritis (OA). A meta-analysis was
      conducted to examine the association between the ASPN D14, D13, and D15 alleles
      and OA of the knee and hip in each ethnic group. In total, 9 studies from eight
      articles involving 4,417 OA patients and 3,403 controls were considered in the
      meta-analysis. Meta-analysis showed no association between OA and the ASPN allele
      coding for 14 D-repeats (D14) in the overall population (OR 1.161, 95 % CI 0.934
      1.444, p = 0.178). Stratification by ethnicity identified no association between
      the ASPN D14 allele and OA in Europeans or Asians (OR 1.035, 95 % CI 0.914-1.173,
      p = 0.589; OR 1.537, 95 % CI 0.899-2.626, p = 0.116), respectively. However, high
      heterogeneity was found in Asians (I (2) = 81.2, p = 0.001). Meta-analysis of OA
      by site showed no association between knee and hip OA and the ASPN D14 allele (OR
      1.240, 95 % CI 0.946-1.627, p = 0.119; OR 1.130, 95 % CI 0.767-1.665, p = 0.537).
      Meta-analysis of D14 versus D13 allele showed the same pattern of OA association
      as the D14 allele. No association was found between the ASPN D13 and D15 alleles
      and risk of developing OA by meta-analysis (OR 0.942, 95 % CI 0.840-1.056, p =
      0.304; OR 1.050, 95 % CI 0.956-1.154, p = 0.306), respectively. This meta
      analysis shows that the ASPN D14, D13, and D15 alleles are not associated with
      the development of OA in Europeans and Asians. Thus, further study of this
      relationship is required in homogenous populations because of the heterogeneity
      of the ASPN D14 allele observed in Asians.

PMID- 24306270
TI  - Large amplitude motion in cold monohydrated dihydrogen phosphate anions H2PO4(
      )(H2O): infrared photodissociation spectroscopy combined with ab initio molecular
      dynamics simulations.
AB  - The vibrational spectroscopy of monohydrated dihydrogen phosphate anions, H2PO4(
      )(H2O), is studied in the O-H stretching (2700-3900 cm(-1)) and the fingerprint
      regions (600-1800 cm(-1)). Assignment of the experimental infrared multiple
      photon photodissociation spectra based on the predicted harmonic spectra of
      energetically low-lying 0 K structures is not conclusive. Ab initio molecular
      dynamics simulations reveal that the water molecule undergoes large amplitude
      motion, even at low internal temperatures, and that the dipole time correlation
      function qualitatively captures the anharmonic effects of the low-barrier
      isomerization reaction on the infrared intensities. 

PMID- 24306269
TI  - Association between TNF-alpha promoter -308 A/G polymorphism and rheumatoid
      arthritis: a meta-analysis.
AB  - The aim of this study was to determine whether the tumor necrosis factor-alpha
      (TNF-alpha) promoter -308 A/G polymorphism is associated with susceptibility to
      rheumatoid arthritis (RA) in populations with different ethnicities. MEDLINE and
      EMBASE databases and manual search were used to identify articles in which TNF
      alpha polymorphism was determined in RA patients and controls. A meta-analysis
      was conducted on the associations between the TNF-alpha -308 A/G polymorphism and
      RA by using (1) allelic contrast and (2) dominant models. A total of 19 studies
      involving 2,584 RA patients and 3,254 controls were considered. The meta-analysis
      showed no association between the TNF-alpha -308 A allele and RA when all the
      subjects were considered [odds ratio (OR) = 1.129, 95 % CI 0.843-1.513, P =
      0.416]. After stratification by ethnicity, the meta-analysis indicated that the A
      allele was significantly associated with RA in Latin Americans (OR = 1.620, 95 %
      CI 1.234-2.111, P = 3.6 * 10(-5)), but not in the European, Arab, or Asian
      populations. The meta-analysis of the AA/AG genotype showed the same pattern of
      results as with the A allele. No association was noted between the AA/AG genotype
      and RA when all the subjects were considered (OR = 1.114, 95 % CI 0.812-1.529, P
      = 0.503), but stratification by ethnicity revealed that the AA/AG genotype was
      significantly associated with RA in Latin Americans (OR = 1.650, 95 % CI 1.234
      2.104, P = 0.001). This meta-analysis showed that the TNF-alpha -308 A/G
      polymorphism may represent a significant risk factor for RA in Latin Americans
      but not in the European, Arab, or Asian populations.

PMID- 24306271
TI  - The utility of human dedifferentiated fat cells in bone tissue engineering in
      vitro.
AB  - We compared the osteoblastic differentiation abilities of dedifferentiated fat
      cells (DFATs) and human bone marrow mesenchymal stem cells (hMSCs) as a cell
      source for bone regeneration therapies. In addition, the utility of DFATs in bone
      tissue engineering in vitro was assessed by an alpha-tricalcium phosphate (alpha
      TCP)/collagen sponge (CS). Human DFATs were isolated from the submandibular of a
      patient by ceiling culture. DFATs and hMSCs at passage 3 were cultured in control
      medium or osteogenic medium (OM) for 14 days. Runx2 gene expression, alkaline
      phosphatase (ALP) activity, as well as osteocalcin (OCN) and calcium contents
      were analyzed to evaluate the osteoblastic differentiation ability of both cell
      types. DFATs seeded in a alpha-TCP/CS and cultured in OM for 14 days were
      analyzed by scanning electron microscopy (SEM) and histologically. Compared with
      hMSCs, DFATs cultured in OM generally underwent superior osteoblastogenesis by
      higher Runx2 gene expression at all days tested, as well as higher ALP activity
      at day 3 and 7, OCN expression at day 14, and calcium content at day 7. In SEM
      analyses, DFATs seeded in a alpha-TCP/CS were well spread and covered the alpha
      TCP/CS by day 7. In addition, numerous spherical deposits were found to almost
      completely cover the alpha-TCP/CS on day 14. Von Kossa staining showed that DFATs
      differentiated into osteoblasts in the alpha-TCP/CS and formed cultured bone by
      deposition of a mineralized extracellular matrix. The combined use of DFATs and
      an alpha-TCP/CS may be an attractive option for bone tissue engineering. 

PMID- 24306272
TI  - Impact of tannic acid on blood pressure, oxidative stress and urinary parameters
      in L-NNA-induced hypertensive rats.
AB  - Hypertension is a major health problem with increasing prevalence around the
      world. Tannic acid is water-soluble polyphenol that is present in tea, green tea,
      coffee, red wine, nuts, fruits and many plant foods. It has been reported to
      serve as an antioxidant or a pro-oxidant depending on the type of cells and its
      concentration. The purpose of our study was to evaluate the effect of tannic acid
      on systolic blood pressure, oxidative stress and some urinary parameters in the
      rat model of essential hypertension. Blood pressures of all rats were measured
      using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L
      arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in
      order to create an animal model of hypertension. Tannic acid was
      intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide
      dismutase, catalase activity and the concentration of malondialdehyde (MDA) were
      determined in blood plasma and homogenates of heart, liver and kidney. In order
      to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid,
      and urea nitrogen values were measured. Compared with the hypertension group, a
      decrease in MDA concentrations of heart tissue (p < 0.01), urea nitrogen values
      (p < 0.01) and urine volumes (p < 0.001) were established in hypertension +
      tannic acid group. There was also a decrease in blood pressure values (20th and
      30th days) of this group, but there was no a statistical difference according to
      hypertension group. The findings of our research show the effect of tannic acid
      in lowering blood pressure in hypertensive rats. 

PMID- 24306275
TI  - Alcohol consumption in early and late pregnancy is associated with poor child
      reading and writing ability at 8-9 years of age.

PMID- 24306273
TI  - Optimization of the isolation and expansion method of human mediastinal-adipose
      tissue derived mesenchymal stem cells with virally inactivated GMP-grade platelet
      lysate.
AB  - Mesenchymal stem cells (MSCs) are adult multipotent cells currently employed in
      several clinical trials due to their immunomodulating, angiogenic and repairing
      features. The adipose tissue is certainly considered an eligible source of MSCs.
      Recently, putative adipose tissue derived MSCs (ADMSCs) have been isolated from
      the mediastinal depots. However, very little is known about the properties, the
      function and the potential of human mediastinal ADMSCs (hmADMSCs). However, the
      lack of standardized methodologies to culture ADMSCs prevents comparison across.
      Herein for the first time, we report a detailed step by step description to
      optimize the isolation and the expansion methodology of hmADMSCs using a virally
      inactivated good manufacturing practice (GMP)-grade platelet lysate, highlighting
      the critical aspects of the procedure and providing useful troubleshooting
      suggestions. Our approach offers a reproducible system which could provide
      standardization across laboratories. Moreover, our system is time and cost
      effective, and it can provide a reproducible source of adipose stem cells to
      enable future studies to unravel new insights regard this promising stem cell
      population. 

PMID- 24306276
TI  - C-type natriuretic peptide in Parkinson's disease: reduced secretion and response
      to deprenyl.
AB  - C-type natriuretic peptide (CNP) is a neurotrophic factor widely expressed in the
      central nervous system including the basal ganglia, limbic system and
      hypothalamus. Nothing is known of CNP's role in the human brain but in rodents
      CNP promotes axon growth and branching, and interacts with dopaminergic function
      in models of addiction. Because preliminary evidence showed reduced levels in
      Parkinson's disease (PD), we examined concentrations of CNP peptides in
      cerebrospinal fluid (CSF) in 146 PD patients from the DATATOP study to determine
      changes over time in relation to medication status and cognitive function. CNP
      and an aminoterminal product of proCNP (NTproCNP) were measured in extracts from
      stored CSF by radioimmunoassay. CSF samples were obtained twice-at enrolment and
      at the study's endpoint (requirement for levodopa treatment) after treatment with
      placebo or deprenyl. At enrolment, median baseline concentration of CSF NTproCNP
      (776 pmol/L, n = 146) was significantly lower than that in a reference group
      without neurological disorder (1,010 pmol/L, p < 0.001). Concentrations declined
      significantly during placebo (p = 0.02) and lower values at enrolment were
      associated with more rapid functional decline (p < 0.01). In contrast, deprenyl-a
      treatment which delayed the need for levodopa-nullified the time-dependent
      decline in CSF NTproCNP. In conclusion subnormal CSF NTproCNP which declines with
      time and associates with increasing functional disability implicates CNP in PD.
      Concordant clinical and peptide responses to deprenyl suggest that some of the
      benefits of monoamine oxidase inhibitors in PD are mediated by preserving tissue
      CNP activity. 

PMID- 24306277
TI  - Relearning auditory spectral cues for locations inside and outside the visual
      field.
AB  - Previous research has demonstrated that, over a period of weeks, the auditory
      system accommodates to changes in the monaural spectral cues for sound locations
      within the frontal region of space. We were interested to determine if similar
      accommodation could occur for locations in the posterior regions of space, i.e.
      in the absence of contemporaneous visual information that indicates any mismatch
      between the perceived and actual location of a sound source. To distort the
      normal spectral cues to sound location, eight listeners wore small moulds in each
      ear. HRTF recordings confirmed that while the moulds substantially altered the
      monaural spectral cues, sufficient residual cues were retained to provide a basis
      for relearning. Compared to control measures, sound localization performance
      initially decreased significantly, with a sevenfold increase in front-back
      confusions and elevation errors more than doubled. Subjects wore the moulds
      continuously for a period of up to 60 days (median 38 days), over which time
      performance improved but remained significantly poorer than control levels. Sound
      localization performance for frontal locations (audio-visual field) was compared
      with that for posterior space (audio-only field), and there was no significant
      difference between regions in either the extent or rate of accommodation. This
      suggests a common mechanism for both regions of space that does not rely on
      contemporaneous visual information as a teacher signal for recalibration of the
      auditory system to modified spectral cues.

PMID- 24306278
TI  - Modeling the time-varying and level-dependent effects of the medial olivocochlear
      reflex in auditory nerve responses.
AB  - The medial olivocochlear reflex (MOCR) has been hypothesized to provide benefit
      for listening in noisy environments. This advantage can be attributed to a
      feedback mechanism that suppresses auditory nerve (AN) firing in continuous
      background noise, resulting in increased sensitivity to a tone or speech. MOC
      neurons synapse on outer hair cells (OHCs), and their activity effectively
      reduces cochlear gain. The computational model developed in this study implements
      the time-varying, characteristic frequency (CF) and level-dependent effects of
      the MOCR within the framework of a well-established model for normal and hearing
      impaired AN responses. A second-order linear system was used to model the time
      course of the MOCR using physiological data in humans. The stimulus-level
      dependent parameters of the efferent pathway were estimated by fitting AN
      sensitivity derived from responses in decerebrate cats using a tone-in-noise
      paradigm. The resulting model uses a binaural, time-varying, CF-dependent, level
      dependent OHC gain reduction for both ipsilateral and contralateral stimuli that
      improves detection of a tone in noise, similarly to recorded AN responses. The
      MOCR may be important for speech recognition in continuous background noise as
      well as for protection from acoustic trauma. Further study of this model and its
      efferent feedback loop may improve our understanding of the effects of
      sensorineural hearing loss in noisy situations, a condition in which hearing aids
      currently struggle to restore normal speech perception.

PMID- 24306279
TI  - Time until treatment equipoise: a new concept in surgical decision making.

PMID- 24306281
TI  - Treatment of cocaine addiction with amphetamine, a sleep-suppressant drug:
      associative learning, sleep patterns and clinical perspectives.

PMID- 24306280
TI  - An organoselenium compound improves behavioral, endocrinal and neurochemical
      changes induced by corticosterone in mice.
AB  - RATIONALE: 3-(4-Fluorophenylselenyl)-2,5-diphenylselenophene (F-DPS) is a
      promising organoselenium compound that shows antidepressant-like properties
      related to interaction with the serotonergic system. OBJECTIVES: In this study, a
      mouse model of anxiety/depressant-like behavior induced by long-term
      corticosterone treatment was used to evaluate behavioral, endocrinal, and
      neurochemical changes in mice and their possible modulation of F-DPS treatment.
      METHODS: Swiss mice were subjected to 4 weeks of corticosterone administration
      (20 MUg/ml in drinking water) and a new therapeutic approach with F-DPS (0.1
      mg/kg/day, intragastric route, during 1 week) was employed to modulate changes
      induced by corticosterone exposure. RESULTS: Treatment with corticosterone caused
      a significant depressant-like behavior in the forced swimming test and tail
      suspension test, which was accompanied by anxiety-like condition in the light
      dark test and novelty suppressed-feeding; similarly to the classical
      antidepressant drug paroxetine, F-DPS treatment was effective in reversing these
      behavioral changes. Further, F-DPS normalized serum levels of corticosterone and
      adrenocorticotropic hormone, which were increased after corticosterone exposure.
      Corticosterone also significantly inhibited glutamate uptake in the prefrontal
      cortex of mice, whereas glutamate release was not modified. Besides normalizing
      glutamate uptake in the corticosterone-exposed mice, F-DPS promoted an inhibition
      of 5-HT uptake in the prefrontal cortex and hippocampus. In addition, hippocampal
      monoamine oxidase-A activity was also inhibited by F-DPS treatment. CONCLUSIONS:
      These findings suggest a modulation of both serotonergic and glutamatergic
      systems by F-DPS after a long-term corticosterone exposure in mice, which may be
      involved in the antidepressant- and anxiolytic-like actions of this
      organoselenium compound.

PMID- 24306282
TI  - Stress, illness, and the social environment: depressive symptoms among first
      generation mandarin speaking Chinese in greater Los Angeles.
AB  - This study documents the indirect effects of social and environmental variables
      as mediated by immigrant stress and physical health. Using data from a large dual
      frame sample of first generation mandarin speaking Chinese immigrants in
      metropolitan Los Angeles counties with the largest groups of Chinese immigrants,
      this study uses a path analytic approach to trace how predictors are related to
      depressive symptoms and to measure direct and indirect influences of variables.
      Although bivariate analyses suggested that many predictors were associated with
      depressive symptoms, multivariate path analysis revealed a more complex structure
      of mediated associations. In the multivariate path analysis only reports of
      physical health and immigrant stress were directly related to depressive symptoms
      (P < 0.05), while acculturation, time in the US, income, US citizenship, and
      distance of persons on whom one could rely were related to stress (but not to
      physical health status) and only to depressive symptoms as mediated by stress.
      Age and educational attainment were related to health status (and to stress as
      mediated by physical health) and to depressive symptoms as mediated by both
      health and stress. These variables were also unrelated directly to health status
      and to depressive symptoms. Associations were evaluated using statistical
      significance, P < 0.05. This study demonstrates the significance of stress and
      health as mediators of variables in the larger context of the physical
      environment and suggests that the mechanisms linking ecological characteristics
      of immigrants to depressive symptoms may be stress and physical health among
      immigrants. 

PMID- 24306283
TI  - Food insecurity, cigarette smoking, and acculturation among Latinos: data from
      NHANES 1999-2008.
AB  - Prevalence of food insecurity (FI) among Latinos in the United States is almost
      double the national average. To better understand FI among Latinos, potential
      risk factors beyond poverty, including acculturation indicators and smoking
      status, were explored. Cross-sectional data from 6,681 Latino adults from the
      1999-2008 National Health and Nutrition Examination Surveys were used. Partial
      proportional odds (PPO) models were used to estimate associations of FI,
      including cigarette smoking and acculturation. The PPO models indicated that
      compared with never smokers, current smokers had significantly higher odds of FI
      (odds ratios ranged from 1.32 to 1.51 across models). Lower levels of
      acculturation and poverty and being a younger or middle-aged adult were also
      significantly associated with FI. Among Latinos, current smoking and low
      acculturation are important risk factors for FI. Current smoking and low
      acculturation may exacerbate nutritional deprivation in a population that is
      already disproportionally affected by poverty and poor health outcomes. 

PMID- 24306284
TI  - Self-reported vicarious trauma in asylum evaluators: a preliminary survey.
AB  - Hundreds of clinicians in the US conduct asylum evaluations, to document evidence
      of torture and persecution of people fleeing their home countries. Participating
      in these encounters puts clinicians at risk for vicarious trauma (VT). Little
      research addressed VT in physicians. Even less is known about VT among asylum
      evaluators. A survey was distributed to members of the asylum network of
      Physicians for Human Rights in Spring 2012. The majority (65%) of survey
      participants denied having experienced VT. However, being female, being a mental
      health professional and having performed a greater number of evaluations was
      associated with a higher likelihood of reporting VT. We present preliminary data
      about VT in asylum evaluators. Recruiters and trainers should make every effort
      to address the issue and educate their volunteers about means of identifying and
      managing symptoms. Formal and informal support services and resources should be
      developed and shared with volunteers.

PMID- 24306285
TI  - Polyacrylic acid@zeolitic imidazolate framework-8 nanoparticles with ultrahigh
      drug loading capability for pH-sensitive drug release.
AB  - The polyacrylic acid@zeolitic imidazolate framework-8 (PAA@ZIF-8) nanoparticles
      (NPs) were first fabricated using a facile and simple route. It is worthwhile
      noting that the as-fabricated PAA@ZIF-8 NPs possessed ultrahigh doxorubicin (DOX)
      loading capability (1.9 g DOX g(-1) NPs), which were employed as pH-dependent
      drug delivery vehicles.

PMID- 24306286
TI  - Administration and environment considerations in computer-based sports-concussion
      assessment.
AB  - Computer-based testing has become a vital tool for the assessment of sport
      related concussion (SRC). An increasing number of papers have been published on
      this topic, focusing on subjects such as the purpose and validity of baseline
      testing, the performance of special populations on computer-based tests, the
      psychometric properties of different computerized neurocognitive tools, and
      considerations for valid and reliable administration of these tools. The current
      paper describes several considerations regarding computerized test design, input
      and output devices, and testing environment that should be described explicitly
      when administering computer-based cognitive testing, regardless of whether the
      assessment is used for clinical or research purposes. The paper also reviews the
      conclusions of recent literature (2007-2013) using computer-based testing for the
      assessment of SRC, with special attention to the methods used in these studies.
      We also present an appendix checklist for clinicians and researchers that may be
      helpful in ensuring proper attention to factors that could influence the
      reliability and validity of computer-based cognitive testing. We believe that
      explicit attention to these technological factors may lead to the development of
      standards for the development and implementation of computer-based tests. Such
      standards have the potential to enhance the accuracy and utility of computer
      based tests in SRC.

PMID- 24306288
TI  - Changing cell-wall compositions in hypocotyls of dark-grown bean seedlings.
AB  - Hypocotyls of dark-grown 6-day-old seedlings of Phaseolus vulgaris L. proved to
      be sufficiently homogeneous to permit studies relating the rate of cell
      elongation to the composition of the primary cell walls. Whereas the levels of
      cellulose and uronic acids remained practically constant during and after cell
      extension, all other components showed major or minor changes. Cell-wall protein,
      as such, decreased by more than 50%, but indications are that hydroxyproline-rich
      glycoprotein increased with a decreasing rate of cell elongation, concomitant
      with a rise in the degree of arabinosylation of wall-bound hydroxyproline. As
      cell elongation slowed down, non-cellulosic glucose accumulated, presumably in
      the form of a beta-(1-4)glucan closely associated with cellulose. These findings
      confirm the notion that the primary cell wall is a highly dynamic structure. 

PMID- 24306287
TI  - Computerized neurocognitive testing in the management of sport-related
      concussion: an update.
AB  - Since the late nineties, computerized neurocognitive testing has become a central
      component of sport-related concussion (SRC) management at all levels of sport. In
      2005, a review of the available evidence on the psychometric properties of four
      computerized neuropsychological test batteries concluded that the tests did not
      possess the necessary criteria to warrant clinical application. Since the
      publication of that review, several more computerized neurocognitive tests have
      entered the market place. The purpose of this review is to summarize the body of
      published studies on psychometric properties and clinical utility of computerized
      neurocognitive tests available for use in the assessment of SRC. A review of the
      literature from 2005 to 2013 was conducted to gather evidence of test-retest
      reliability and clinical validity of these instruments. Reviewed articles
      included both prospective and retrospective studies of primarily sport-based
      adult and pediatric samples. Summaries are provided regarding the available
      evidence of reliability and validity for the most commonly used computerized
      neurocognitive tests in sports settings.

PMID- 24306289
TI  - Dependence of the membrane potential of Chara cells on external pH in the
      presence or absence of internal adenosinetriphosphate.
AB  - The dependence of the membrane potential (Em) and the membrane resistance (Rm) of
      Chara australis R. Brown on the pH of the external medium (pH0) was studied by
      controlling the activity of the plasmamembrane H(+) pump under both light and
      dark conditions. The activity of the pump was controlled by regulating the
      internal ATP or Mg(2+) concentration in tonoplast-free cells prepared by vacuolar
      perfusion. In these cells, which contained Mg . ATP (mgATP cells), Em and Rm were
      very sensitive to pH0, as in normal cells. Em was more negative in light than in
      the dark at all pH0 values tested. Tonoplast-free cells with very low [ATP]i (
      ATP cells) or [Mg(2+)]i (-Mg cells) showed very weak dependence of Em and Rm on
      pH0. Thus, the active and not the passive component of Em was sensitive to pH0.
      At the same time, the high permeability of the plasma membrane to H(+) was
      questioned. In both-ATP cells and-Mg cells, Em was scarcely affected and Rm
      markedly decreased on illumination. 

PMID- 24306290
TI  - Photosynthesis and the intracellular inorganic carbon pool in the bluegreen alga
      Anabaena variabilis: Response to external CO2 concentration.
AB  - The apparent photosynthetic affinity of A. variabilis to CO2 is greatly affected
      by the CO2 concentration in the medium during growth. Halfmaximal rate of
      photosynthetic O2 evolution is achieved at 10 MUM and 100 MUM inorganic carbon
      (Cinorg) in cells grown at low-CO2 (air) and high CO2 (5% v/v CO2 in air),
      respectively, whilst the maximum rate of photosynthesis is similar in both cases.
      Both high- and low-CO2-grown Anabaena accumulate Cinorg within the cell; however,
      the rate of accumulation and the steady-state internal Cinorg concentration
      reached is much higher in low as compared with high-CO2-grown cells. It is
      suggested that Anabaena cells actively accumulate Cinorg. Measurements of the
      kinetics of Cinorg transport indicate that the affinity of the transport
      mechanism for Cinorg is similar (Km(Cinorg(?150 MUM) in both high- and low-CO2
      grown cells. However, V max is 10-fold higher in the latter case. It is suggested
      that this higher V max for transport is the basis of the superior capability to
      accumulate Cinorg and the higher apparent photosynthetic affinity for external
      Cinorg in low-CO2-grown Anabaena. Carbonic anhydrase activity was not detectable
      in Anabaena, yet both photosynthetic affinity to Cinorg in the medium (but not V
      max) and the rate of accumulation of Cinorg were inhibited by the carbonic
      anhydrase inhibitor ethoxyzolamide. 

PMID- 24306291
TI  - Characterization of a maturation-specific mRNA in dry mung bean embryonic axes.
AB  - The poly(A)-rich RNA from dry mung bean (Vigna radiata [L.] Wilczek) embryonic
      axes has been isolated and translated in a wheat embryo cell-free system, and the
      products were analyzed on sodium dodecyl sulfate-polyacrylamide gels. The
      fluorographyic patterns showed a heavy band at approximately MW 12,000. The
      messenger RNA coding for this polypeptide disappeared in the course of early
      germination. This messenger is translated in vivo but simultaneously degrades
      when the axes imbibe. The poly(A)-rich RNA from dry axes has been fractionated on
      sucrose-dimethyl sulfoxide gradients, and this messenger has been found to be
      distributed largely in the 9-14 S region. The polypeptide synthesized in vitro
      has been immunoprecipitated, using the antiserum raised against this protein
      purified from dry axes. 

PMID- 24306292
TI  - Isolation and function of a low molecular weight protein of mung bean embryonic
      axes.
AB  - A low molecular weight protein from dry mung bean (Vigna radiata) embryonic axes
      has been purified to near homogeneity by chromatography on DEAE-cellulose and
      hydroxylapatite. It shows a molecular weight of about 12,000 in sodium dodecyl
      sulfate-polyacrylamide gels and a sedimentation coefficient of about 2 S in
      sucrose gradients. This protein occurs in greater amounts in dry axes than in dry
      cotyledons, and it dramatically disappears during early germination of the seed.
      Affinity chromatography tests do not indicate it as a trypsin inhibitor or as a
      glycoprotein. It is a water-soluble cytoplasmic protein exhibiting an amino acid
      composition characteristic of storage proteins with a high content of glutamic
      acid/glutamine. We suggest that it is a low molecular weight storage albumin. 

PMID- 24306293
TI  - Nitrogen redistribution during grain growth in wheat (Triticum aestivum L.) : II.
      Chloroplast senescence and the degradation of ribulose-1,5-bisphosphate
      carboxylase.
AB  - The flag leaf of wheat was examined for changes in quantity and activity of
      ribulose-bisphosphate carboxylase (RuBPCase; EC 4.1.1.39), in the proteolytic
      degradation of RuBPCase and other native proteins, and in the ultrastructure of
      the leaf cells during grain development. Proteolytic degradation of RuBPCase at
      pH 4.8 increased until 8-10 d after anthesis, then declined, and increased again
      16-18 d after anthesis. The second peak coincided with the onset of a
      preferential loss of immunologically recognizable RuBPCase. The specific activity
      and number of active sites per molecule of RuBPCase did not change during
      senescence. Examination of ultrastructure with the electron microscope showed
      little change in the appearance of the mitochondria as the flag leaf aged.
      Prominent cristae were still evident 35 d after anthesis. In contrast, the
      chloroplasts showed a progressive disruption of the thylakoid structure and an
      increasing number of osmiophilic glubules. The double membrane envelope
      surrounding the chloroplast appeared intact until at least 20 d after anthesis.
      The tonoplast also appeared intact up to 20 d. At later stages of senescence of
      the leaf the outer membrane of the chloroplast adjacent to the tonoplast appeared
      to break but the inner membrane of the envelope appeared intact until at least 35
      d after anthesis. 

PMID- 24306294
TI  - Nature of the phytochrome effect on the binding of glycolate oxidase to
      peroxisomes in vitro.
AB  - The attachment of glycolate oxidase to the peroxisomal fraction derived from
      etiolated barley leaves (Hordeum vulgare L. cr. Dvir) is affected by light. The
      effect of red irradiation is reversed by subsequent far-red irradiation,
      indicating the involvement of phytochrome. This phytochrome effect is assumed to
      be related to phytochrome binding. Indeed, prevention by filipin (1.2.10(-6) mol
      g(-1) f wt) or cholesterol of phytochrome binding to membranes abolishes the
      effect of light on the interaction between glycolate oxidase and the peroxisomal
      fraction. Glycolate oxidase binding is affected by addition of quasi-ionophores
      such as gramicidin and filipin at a concentration of 0.6.10(-3) mol g(-1) f wt.
      This fact indicates that peroxisome-glycolate oxidase interaction may be affected
      by membrane potential. Since both ion transport and membrane potential are known
      to be affected by phytochrome, it is proposed that phytochrome acts in the light
      induced modulation of glycolate oxidase attachment as a quasi-ionophore. 

PMID- 24306295
TI  - Pollen-pistil interaction in Linum grandiflorum : Scanning electron microscopic
      observations and proteins of the stigma surface.
AB  - A detailed investigation of the receptive surface of the stigma of a dimorphic
      taxon, Linum grandiflorum, was carried out using scanning electron microscopy,
      cytochemistry and polyacrylamide gel electrophoresis. The stigma surfaces of the
      pin and thrum morphs showed distinct differences. The stigma of the pin morph was
      of the dry type and the papillae were covered with a uniform cuticle-pellicle
      layer. The stigma of the thrum morph, on the other hand, resembled the wet type;
      the cuticle-pellicle layer was disrupted at places and a secretion product was
      released onto the surface of the stigma. Coomassie blue staining material was
      present on the surface of only the thrum stigma. Although esterases and acid
      phosphatases were present on the stigma of both the morphs, their activity was
      invariably higher on the thrum stigma. Polyacrylamide gel electrophoresis of
      stigma leachates also showed distinct differences in the protein profiles of the
      two morphs. 

PMID- 24306296
TI  - In vitro synthesis of barley storage proteins.
AB  - Membrane-bound polysomes were isolated from developing endosperms of barley
      (Hordeum vulgare L.) and shown to support the synthesis of trichloroacetic acid
      insoluble material by an in vitro wheat germ protein synthesis system. The mRNA
      associated with the polysomes was separated from the ribosomes by affinity
      chromatography on oligo-dT cellulose and was also shown to support in vitro
      protein synthesis. The poly-A(+) RNA isolated contained material of between 0.55
      and 2.55 kilobases in length with about 6% poly A. The products of in vitro
      protein synthesis resembled hordeins (the prolamin storage proteins of the barley
      endosperm) in that they were predominantly soluble in 55% propan-2-ol, contained
      a low proportion of lysine as compared with leucine and had similar, but not
      identical, electrophoretic properties. The differences in the electrophoretic
      behaviour between the products of poly-A(+) RNA translation and authentic
      hordeins is suggested to be due to the presence of an extra (leader?) sequence on
      the former. 

PMID- 24306297
TI  - Gibberellins and the photoperiodic control of stem elongation in the long-day
      plant Agrostemma githago L.
AB  - Agrostemma githago is a long-day rosette plant in which transfer from short days
      (SD) to long days (LD) results in rapid stem elongation, following a lag phase of
      7-8 d. Application of gibberellin A20 (GA20) stimulated stem elongation in plants
      under SD, while 2-isopropyl-4-dimethylamino-5-methylphenyl-1-piperidine
      carboxylate methyl chloride (AMO-1618, an inhibitor of GA biosynthesis) inhibited
      stem elongation in plants exposed to LD. This inhibition of stem elongation by
      AMO-1618 was overcome by simultaneous application of GA20, indicating that GAs
      play a role in the photoperiodic control of stem elongation in this species.
      Endogenous GA-like substances were analyzed using reverse-phase high-performance
      liquid chromatography and the d-5 corn (Zea mays L.) assay. Three zones with GA
      like activity were detected and designated, in order of decreasing polarity, as
      A, B, and C. A transient, 10-fold increase in the activity of zone B occurred
      after 8-10 LD, coincident with the transition from lag phase to the phase of
      rapid stem elongation. After 16 LD the activity in this zone had returned to a
      level similar to that under SD, even though the plants were elongating rapidly by
      this time. However, when AMO-1618 was applied to plants after 11 LD, there was a
      rapid reduction in the rate of stem elongation, indicating that continued GA
      biosynthesis was necessary following the transient increase in activity of zone
      B, if stem elongation was to continue under LD. It was concluded that control of
      stem elongation in A. githago involves more than a simple qualitative or
      quantitative change in the levels of endogenous GAs, and that photoperiodic
      induction alters both the sensitivity to GAs and the rate of turnover of
      endogenous GAs. 

PMID- 24306298
TI  - The effect of photoperiod on the levels of seven endogenous gibberellins in the
      long-day plant Agrostemma githago L.
AB  - The following seven gibberellins (GAs) have been identified by gas chromatography
      mass spectrometry in shoots and leaves of the long-day plant Agrostemma githago:
      GA53, GA44, GA19, GA17, GA20, GA1, and 3-epi-GA1. The levels of these compounds
      were measured, using selected ion monitoring, during photoperiodic induction. The
      levels of GA44, GA19, GA17, and GA20 all increased to a peak at eight long days
      (LD), followed by a decline, while the levels of GA1 and 3-epi-GA1 did not reach
      a peak until 12 LD. The level of GA53 remained steady over the first 10-12 LD.
      Later in the LD treatment the levels of GA53, GA44, GA19, and GA17 increased
      again. The rate of metabolism of all GAs except GA53 was higher after 12-16 LD
      than under short days. These data thus provide indirect evidence for an effect of
      photoperiodic induction on GA turnover in A. githago. 

PMID- 24306299
TI  - Mechanical stabilization of guard cell protoplasts of Vicia faba.
AB  - Guard cell protoplasts of Vicia faba were immobilized in cross-linked Ca
      alginate. No visible morphological changes were detected under the light
      microscope over a period of 14 days. The entrapped cells reacted normally to
      changes of the external osmolarity by shrinking and swelling. Addition of the
      calcium complexing agent, citrate, led to dissolution of the matrix. After
      reequilibration with Ca ions the released cells regained their ability to swell
      and shrink in response to external stress. The released protoplasts could be
      stained with the vital dye, neutral which was accumulated in the vacuoles. It
      should also be noted that the protoplasts can be transported when immobilized. 

PMID- 24306300
TI  - Anthocyanin accumulation and PAL activity in a suspension culture of Daucus
      carota L. : Inhibition by L-alpha-aminooxy-beta-phenylpropionic acid and t
      cinnamic acid.
AB  - Cells of Daucus carota grown in a liquid medium produced large amounts of
      cyanidin as the only flavonoid aglycon. After inoculation in fresh medium a
      maximum activity of phenylalanine ammonia lyase (PAL; EC 4.3.1.5) was observed
      within 24 h. L-alpha-aminooxy-beta-phenylpropionic acid (L-AOPP), thought to be a
      competitive inhibitor of PAL, inhibited cyanidin accumulation up to 80%. In order
      to study the regulatory role of PAL, the effects of L-AOPP and t-cinnamic acid,
      the product of the deamination of phenylalanine, were investigated. Cinnamic
      acid, applied in vivo (10(-4) M), was not able to compensate for the inhibition
      of cyanidin production caused by L-AOPP (10(-4) M) in the same sample. Carrot
      cells treated with L-AOPP exhibited a "super-induction" of PAL already described
      for gherkin hypocotyls (Amrhein and Gerhardt 1979). This effect was not
      influenced by t-cinnamic acid. L-AOPP seems to be a very specific inhibitor since
      it affected neither growth nor soluble protein content, whereas t-cinnamic acid
      inhibited both. Investigations on the content of soluble amino acids in L-AOPP
      treated cells revealed a specific accumulation of soluble phenylalanine, whereas
      treatment with t-cinnamic acid led to an increase of amino acids in general, thus
      indicating that the latter compound has a rather unspecific effect on cellular
      metabolism. In vitro studies with PAL isolated from Daucus carota revealed that L
      AOPP inhibited the enzyme at very low doses (K I=2.4.10(-9)), whereas t-cinnamic
      acid, by comparison, affected the enzyme at high concentrations (K I=1.8.10(-4)).

PMID- 24306301
TI  - The control of food mobilization in seeds of Cucumis sativus L. : III. The
      control of protein degradation.
AB  - An analysis of the in vitro activities of proteolytic enzymes from cotyledons of
      germinating cucumber seeds has been carried out and the effects of protein
      degradation products on such activities monitored. Aminopeptidase activity is
      substantially inhibited with either L-leucine or L-phenylalanine and trypsin
      activity with L-arginine. Aminopeptidase activity was also markedly reduced in
      the presence of individual di- and tripeptides. Of the peptides tested, however,
      only L-tryptophyl-L-phenylalanine inhibited the degradation of native cucumber
      seed protein by the endogenous cucumber seed protease(s) (autodigestive
      activity). 

PMID- 24306302
TI  - A clonal analysis of anthocyanin accumulation by cell cultures of wild carrot.
AB  - The accumulation of anthocyanin by clones and subclones from a cell suspension
      culture of wild carrot (Daucus carota L.) has been measured under standard
      conditions. Clones which accumulate low amounts of anthocyanin were shown, by
      recloning after maintenance by serial passage, to have become heterogenous and to
      contain cells with increased accumulation of anthocyanin. There appears to be a
      maximum amount of anthocyanin that clones can accumulate. Clones which accumulate
      the maximum amount of anthocyanin were shown by recloning after maintenance by
      serial passaging, to have become heterogenous and to contain many cells which
      accumulate less than the maximum possible amount of anthocyanin. When clones
      which accumulate the maximum amount of anthocyanin are maintained by serial
      passage, the decline in anthocyanin accumulation is different in different media.
      The results indicate that the changes in the ability of cells to accumulate
      anthocyanin involve no qualitative change in the genetic information of the
      cells, i.e., the changes are not the consequence of mutations. 

PMID- 24306303
TI  - X-ray microanalysis and chlorotetracycline staining of calcium vesicles in the
      green alga Mougeotia.
AB  - Calcium ions have been proposed to play a key role in the sensory transduction of
      phytochrome-governed chloroplast movement in the green alga Mougeotia. To test
      this hypothesis, the intracellular pattern of calcium distribution was studied in
      this alga by two independent techniques, namely, X-ray microanalysis of fixed and
      of unfixed frozen-hydrated cells, as well as in vivo fluorescence by
      chlorotetracycline. Both methods of detection reveal a significant
      compartmentation of calcium in vesicles close to the chloroplast edge and, less
      frequently, in the cortical cytoplasm. Microfilaments, presumably actin, which
      could function in driving chloroplast movement, have been observed running
      between the chloroplast edge and the cortical cytoplasm (Wagner, G., Klein, K.
      (1978) Photochem. Photobiol. 27, 137). The vesicular calcium concentration is
      stable and decays only slowly in the absence of extracellular calcium much in the
      same way as the ability of the chloroplast to perform movements decreases. A
      functional relationship between vesicular calcium compartmentation and
      phytochrome-governed chloroplast movement in the green alga Mougeotia seems
      indicated. 

PMID- 24306304
TI  - Glucan synthesis by intact cotton fibres fed with different precursors at the
      stages of primary and secondary wall formation.
AB  - Seed clusters of individual locules from fruit capsules of Gossypium arboreum L.
      with adhering intact fibres were fed with radioactive uridinediphosphoglucose
      (UDPG), guanosinediphosphoglucose (GDPG), glucose and sucrose. The incorporation
      into high molecular weight glucans of the fibres was studied. For primary wall
      fibres, UDPG at 1 mM was by far the best precursor, whereas sucrose was the best
      precursor for secondary wall fibres. No competition was observed between the
      incorporation of glucose from UDPG and from sucrose when the two were fed
      simultaneously to secondary wall fibres, indicating that their metabolic pathways
      are well separated when they are fed from the apoplast. Inhibitors of respiratory
      ATP-formation strongly inhibited incorporation of sucrose but not that of UDPG.
      Sucrose incorporation was studied at five different stages of development of the
      cotton fibres. At the stage of most intense secondary wall formation the
      incorporation rate was about 300 times that during primary wall formation (24
      days post anthesis (DPA)). Incorporation from 1 mM UDPG or GDPG by secondary wall
      fibres (35 DPA) was less than twice that of primary wall fibres (22 DPA),
      indicating that the two sugar nucleotides are not readily used as precursors for
      secondary wall cellulose when they are fed to the exterior of intact cells. The
      high molecular weight non-cellulosic glucans formed from UDPG and sucrose at 5
      and 1,000 MUM were solubilized in strongly alkaline solutions or dimethyl
      sulfoxide (DMSO) and were partially characterized by degradation with an exo-beta
      1,3-glucanase. After feeding for one hour, at most 1/3 of the radioactivity in
      high molecular weight material was found in cellulose and at least 2/3 in beta
      1,3-glucan. The proportions varied little for fibres in the age range of 30 to 48
      DPA when sucrose was the precursor although the total incorporation varied by a
      factor of about four. The fact that at all stages of secondary wall formation
      beta-1,3-glucan is synthesized at a very high rate, but that the total amount in
      the cell wall does not exceed 2% in the later stages of wall formation, can be
      interpreted in terms of a high turnover of this polysaccharide if it is assumed
      that wound effects are negligible in the system under study. 

PMID- 24306305
TI  - Spectral properties of soluble and pelletable phytochrome from epicotyls of
      etiolated pea seedlings.
AB  - The red-light(R)-absorbing form of phytochrome (Pr) was detected
      spectrophotometrically in a 20,000 g particulate fraction prepared from a 1,000 g
      supernatant fraction from epicotyl tissue of pea (Pisum sativum L.) seedlings
      grown in the dark and only briefly exposed to dim green light. The difference
      spectrum of phytochrome in this fraction was essentially the same as that of
      soluble phytochrome from the same tissue. When the non-irradiated 20,000 g
      particulate fraction was incubated in the dark at 25 degrees  C, an absorbance
      change (decrease) of Pr after actinic red irradiation was found only in the far
      red (FR) region. When the 20,000 g particulate fraction was irradiated with R and
      then incubated in the dark, the FR-absorbing form of phytochrome (Pfr)
      disappeared spectrally at a rate about half that in the soluble fraction, and the
      difference spectrum of the Pr which became detectable after dark incubation of
      the 20,000 g particulate fraction was markedly distorted. In contrast, Pfr in a
      20,000 g particulate fraction prepared from tissues irradiated with R did not
      change optically during dark incubation at 25 degrees  C for 60 min, while Pfr in
      the soluble fraction from the same tissue disappeared in the dark. No
      dissociation of either Pr or Pfr from the 20,000 g particulate fraction was
      indicated during a 60-min dark incubation at 25 degrees  C, but Pfr in a 20,000 g
      particulate fraction prepared in vitro from R-irradiated 1,000 g supernatant
      fraction in the presence of CaCl2 disappeared spectrally and the difference
      spectrum of Pr in the 20,000 g particulate fraction became quite distorted during
      the dark incubation. 

PMID- 24306306
TI  - Demonstration of C3-photosynthesis in a bluegreen alga, Coccochloris peniocystis.
AB  - Air-grown cells of the cyanobacterium, Coccochloris peniocystis Kutz were exposed
      to [(14)C] bicarbonate in the light for periods of 0.5 to 2.0 s followed by
      longer exposures to unlabelled bicarbonate. Although C4 acids are among the
      initial products of photosynthesis, the kinetics of tracer movement during the
      pulse-chase experiments demonstrate that the principal mechanism of CO2 fixation
      in this alga is the C3-pathway. 

PMID- 24306307
TI  - Youthful smoking and drinking in a longitudinal perspective.
AB  - The incidence and continuity of smoking and drinking, precursory social
      behavioral characteristics of smokers and drinkers, and life conditions related
      to smoking and drinking are described. The study was part of an extensive Finnish
      longitudinal study of social development, the original sample of which consisted
      of 8-year-old subjects (196 boys, 173 girls) studied in 1968 by employing peer
      nomination and teacher ratings. The follow-up studies were made at ages 14 and
      20. 154 Ss at age 14 and 135 Ss at age 20 were interviewed about their smoking
      and drinking habits, among others. The results showed that about 20% of the
      subjects smoked at age 14 and about 30% at age 20. The proportion of abstainers
      was about 25% at age 14 and 10% at age 20. The differences between the sexes were
      negligible. Smoking at age 20 was predictable on the basis of early initiation,
      but drinking was not. Aggressiveness at age 8, and orientation towards peers and
      negativism at age 14 predicted male and female smoking and male drinking and
      alcohol offences at age 20. Social characteristics did not predict female
      drinking. At age 20, male and female smoking and heavy drinking belonged to the
      way of life of Reveller, and smoking also to that of Loser. Smoking and drinking
      were related to parental models at age 20, but in puberty the influence of peers'
      smoking and drinking was stronger than that of the parental models. Lack of
      parental encouragement and affectional interaction with the parents was related
      to female smoking and male drinking. Youthful smoking and drinking were not
      connected with family socioeconomic status. 

PMID- 24306308
TI  - Social support factors and drinking among college student males.
AB  - The present investigation focused on social support and social competence among
      male college freshmen and the relation of these variables to alcohol use and
      psychological adjustment. Recent critical analyses of the social support
      literature suggest that studies in this area have generally failed to distinguish
      between different modes of support. Therefore, measures pertaining to possible
      dimensions of the social support construct (i.e., social network characteristics
      and perceived social support) were administered to 137 male college freshmen,
      along with a measure of social competence, and these data were factor analyzed.
      As a result, three interpretable factors were identified: Network Functions,
      Perceived Intimacy/Support, and Social Competence. Measures representing social
      network characteristics (e.g., network size, density, amount of social contact),
      perceived support, and social competence were used to predict alcohol use and
      psychological symptomatology. Results indicated that alcohol use was positively
      related to social network characteristics that reflect high levels of social
      interaction (e.g., network density, amount of social contact) and measures of
      social competence. Drinking was not significantly related to measures of
      perceived social support. Psychological symptomatology was negatively related to
      measures of perceived support, social competence, and network density. Thus, this
      study concludes that different modes of support and different measures of
      psychological adjustment should not be treated as if they are equivalent. And
      this study reaffirms a growing concern that the social context provides frequent
      opportunities for alcohol use and abuse in a college community. 

PMID- 24306309
TI  - Ego development in the college years: Two longitudinal studies.
AB  - Students from a two-year and a five-year college were tested twice at four-and
      four-and-a-half-year intervals using the Sentence Completion Test of Ego
      Development. In both samples retest scores were positively correlated with
      initial scores (0.39 and 0.49) and were significantly higher in ego level
      (typically a half-stage). These data are consistent with the developmental
      hypothesis that ego growth occurs according to a fixed sequence of stages, and
      suggest that rate of growth decreases with age. In one sample women were higher
      in ego level than men at the beginning of the study, but in neither sample were
      sex differences significant at retest. 

PMID- 24306310
TI  - Types of neutralization and types of delinquency.
AB  - Neutralization theory was tested with questionnaires administered to a random
      sample of public school students (N=298) and institutionalized male delinquents
      (N=53). Nye-Short delinquency items were factor analyzed to yield three
      dimensions of delinquency (Predatory, Minor, and Aggressive), and each of the
      five techniques of neutralization was scored separately. Patterns of acceptance
      of neutralization techniques were similar among high school males, high school
      females, and institutionalized males. For example, all three subsamples scored
      highest on Detail of a Victim and lowest on Appeal to Higher Loyalties.
      Correlations between each technique of neutralization and each type of
      delinquency, however, were statistically significant and quite dissimilar. Within
      the three subsamples, however, there were no discernible patterns among these
      dissimilar correlations. In fact, few of the differences among these correlations
      were statistically significant. The analysis provides general support for
      neutralization theory, but indicates that the particular technique of
      neutralization as well as the particular type of delinquent act may be viable
      distinctions in delinquency research. 

PMID- 24306311
TI  - Correlates of early adolescent peer and personal substance use in rural northern
      Michigan.
AB  - Data were collected from 181 middle school students in rural northern Michigan
      during May 1982. Student responses concerning peer and personal use of alcohol
      and nicotine were analyzed. The results suggest that peer substance use is highly
      correlated with personal substance use, and increases significantly with age.
      Sexual differences were also noted. This article describes the powerful
      correlates between peer and personal alcohol and nicotine use (i.e., cigarette
      smoking), and suggests some hypotheses for this phenomenon. 

PMID- 24306312
TI  - Attitudes of Senegalese schoolgoing adolescents towards tobacco smoking.
AB  - Results show that tobacco smoking is a widespread phenomenon among Senegalese
      adolescents for several important reasons: economic (the intensive advertisement
      campaigns in favor of tobacco smoking), cultural (the ambivalence of traditional
      attitudes of Western urbanization, and the attractiveness of the Western way of
      life), psychological (the traumas of modernism on a basically poor developing
      country). Despite this alarming picture, signs point to an effective preventive
      strategy aimed mainly at schoolgoing adolescents and based on joint legal,
      scientific, cultural, and even religious action. 

PMID- 24306313
TI  - Stabilization and transformation of asymmetric configurations in small-mismatch
      alloy nanoparticles: the role of coordination dependent energetics.
AB  - Chemical order in platinum-iridium truncated-octahedron nanoparticles as a model
      system was studied using coordination-dependent bond-energy variations (CBEV) and
      the statistical-mechanical free-energy concentration expansion method (FCEM)
      adapted for handling axially symmetric structures. Pt-Ir side-separated ("Quasi
      Janus", QJ) configurations are found to be stabilized at low temperatures mainly
      due to CBEV-related preferential strengthening of Pt-surface-Ir-subsurface bonds,
      and the greatly reduced number of hetero-atomic bonds. In comparison, the roles
      of local strain (by only ~2% atomic mismatch), short-range-order and vibrational
      entropy are minor. At higher temperatures, the QJ configuration is transformed
      into a partially disordered central-symmetric onion-like structure, and the sharp
      transition is accompanied by extensive pre-transition atomic exchange processes,
      reflected in a lambda-type heat capacity curve. The nanoparticle composition and
      size dependent transition temperatures, which are well below the bulk miscibility
      gap, furnish the first Pt-Ir nanophase diagram, which is likely to represent a
      distinct class of asymmetrically phase-separated nanoalloys having negligible
      mismatch but large preferential bond strengthening at the near-surface region.

PMID- 24306314
TI  - Exploratory study of carboplatin plus the copper-lowering agent trientine in
      patients with advanced malignancies.
AB  - PURPOSE: Preclinical data showed that trientine, a copper-lowering agent, re
      sensitized cancer cells to carboplatin through enhanced human copper transporter
      1 (hCtr1) -mediated platinum uptake. EXPERIMENTAL DESIGN: We studied carboplatin
      and trientine in patients (n = 55; 45 who had failed platinum) with advanced
      malignancies (Phase I, modified 3 + 3 design). RESULTS: The most common cancers
      were head and neck (n = 13), non-small cell lung (n = 10) and epithelial ovarian
      (n = 8). The median number of prior regimens was four. No dose-limiting toxicity
      or treatment-related deaths were observed at doses up to carboplatin AUC 6 given
      with trientine. Eight patients achieved stable disease (SD) >= 6 months (six
      platinum failures) and one patient with platinum-resistant ovarian cancer,
      partial response (PR) (total SD >= 6 months/PR = 9, 16.4 %). The mean nadir serum
      copper level in the nine patients with SD >= 6 months/PR was 0.55 MUg/mL (95 %
      CI, 0.34-0.75) versus 1.22 MUg/mL (95 % CI, 1.02-1.42) (p < 0.001) in 38 tested
      patients with progression. In patients who maintained their ceruloplasmin (major
      copper-carrying protein) levels at 5-15 mg/dL (n = 9), the median progression
      free and overall survivals were 9.2 and 15.2 months versus 1.9 (p = 0.001) and
      5.7 months (p = 0.033) in patients who did not (n = 38), respectively.
      CONCLUSIONS: The combination of a copper-lowering agent with carboplatin was well
      tolerated and associated with antitumor activity, especially in patients in whom
      copper and/or ceruloplasmin levels were lowered. Further investigation of this
      strategy for reversing platinum resistance is warranted.

PMID- 24306316
TI  - pH-controlled assembly of hybrid architectures based on Anderson-type
      polyoxometalates and silver coordination units.
AB  - Three new architectures based on Anderson-type polyoxometalates, (3-H2pya)[(3
      Hpya)2Ag][AgAlMo6H6O24].3H2O 1, HNa2[(3-pya)(3-Hpya)Ag]2[AlMo6H6O24].8H2O 2 and
      [(3-Hpya)2Ag][(H2O)2Ag]2[AlMo6H6O24].2H2O 3 (3-Hpya = 3-(3-pyridyl)acrylic acid),
      have been synthesized at the different pH values and characterized by elemental
      analysis, IR spectroscopy, TG analysis, powder X-ray diffraction and single
      crystal X-ray diffraction. Compound 1 was obtained at lower pH value (2.50), and
      represents a 3D host-guest compound containing the Ag-3-Hpya coordination complex
      guest and the 3D [AgAlMo6H6O24](2-) host. The host framework exhibits a 4
      connected diamond topology, and is constructed from [AlMo6H6O24](3-) clusters
      connected by Ag(+) cations. When the pH value was increased slightly, compound 2
      was obtained with a 1D chain structure built up of Anderson polyoxoanions, Ag-3
      Hpya coordination complexes and binuclear sodium clusters. By further increasing
      the pH value (3.50), compound 3 was isolated as a 2D network in which
      [AlMo6H6O24](3-) clusters are linked together by Ag(+) cations and Ag-3-Hpya
      coordination complexes. Their structural differences reveal that the pH value of
      the reaction system is the key factor influencing the structure and topology of
      three compounds. The UV-visible-NIR diffuse reflectivity spectra of 1-3 show that
      they can be regarded as a wide gap semiconductor. Furthermore, the pyrolysis of 1
      3 produces three nanocomposites 1'-3' composed of silver microparticles dispersed
      in the metal oxides. The photocatalytic properties of 1'-3' have been
      investigated. 

PMID- 24306317
TI  - Meiotic chromosome pairing behaviour of natural tetraploids and induced
      autotetraploids of Actinidia chinensis.
AB  - Non-preferential chromosome pairing was identified in tetraploid Actinidia
      chinensis and a higher mean multivalent frequency in pollen mother cells was
      found in colchine-induced tetraploids of A. chinensis compared with naturally
      occurring tetraploids. Diploid and tetraploid Actinidia chinensis are used for
      the development of kiwifruit cultivars. Diploid germplasm can be exploited in a
      tetraploid breeding programme via unreduced (2n) gametes and chemical-induced
      chromosome doubling of diploid cultivars and selections. Meiotic chromosome
      behaviour in diploid A. chinensis 'Hort16A' and colchicine-induced tetraploids
      from 'Hort16A' was analysed and compared with that in a diploid male and
      tetraploid males of A. chinensis raised from seeds sourced from the wild in
      China. Both naturally occurring and induced tetraploids formed multivalents, but
      colchicine-induced tetraploids showed a higher mean multivalent frequency in the
      pollen mother cells. Lagging chromosomes at anaphase I and II were observed at
      low frequencies in the colchicine-induced tetraploids. To investigate whether
      preferential or non-preferential chromosome pairing occurs in tetraploid A.
      chinensis, the inheritance of microsatellite alleles was analysed in the
      tetraploid progeny of crosses between A. chinensis (4x) and A. arguta (4x). The
      frequencies of inherited microsatellite allelic combinations in the hybrids
      suggested that non-preferential chromosome pairing had occurred in the tetraploid
      A. chinensis parent.

PMID- 24306318
TI  - High-resolution analysis of a QTL for resistance to Stagonospora nodorum glume
      blotch in wheat reveals presence of two distinct resistance loci in the target
      interval.
AB  - Stagonospora nodorum glume blotch (SNG), caused by the necrotrophic fungus
      Stagonospora nodorum, is one of the economically important diseases of bread
      wheat (Triticum aestivum L.). Resistance to SNG is known to be quantitative and
      previous studies of a recombinant inbred line (RIL) population identified a major
      quantitative trait locus (QTL) for resistance to SNG on the short arm of
      chromosome 3B. To localize this QTL (QSng.sfr-3BS) with high resolution, we
      constructed a genetic map for the QTL target region using information from
      sequenced flow-sorted chromosomes 3B of the two parental cultivars 'Arina' and
      'Forno', the physical map of chromosome 3B of cultivar 'Chinese Spring' and BAC
      clone sequences. The mapping population of near-isogenic lines (NIL) was
      evaluated for SNG resistance in field infection tests. NILs segregated for
      disease resistance as well as for plant height; additionally, we observed a high
      environmental influence on the trait. Our analysis detected a strong negative
      correlation of SNG resistance and plant height. Further analysis of the target
      region identified two linked loci associated with SNG resistance. One of them was
      also associated with plant height, revealing an effect of QSng.sfr-3BS on plant
      height that was hidden in the RIL population. This result demonstrates an
      unexpectedly high genetic complexity of resistance controlled by QSng.sfr-3BS and
      shows the importance of the study of QTL in mendelized form in NILs. 

PMID- 24306319
TI  - SSR marker-assisted improvement of fiber qualities in Gossypium hirsutum using G.
      barbadense introgression lines.
AB  - This study demonstrates the first practical use of CSILs for the transfer of
      fiber quality QTLs into Upland cotton cultivars using SSR markers without
      detrimentally affecting desirable agronomic characteristics. Gossypium hirsutum
      is characterized by its high lint production and medium fiber quality compared to
      extra-long staple cotton G. barbadense. Transferring valuable traits or genes
      from G. barbadense into G. hirsutum is a promising but challenging approach
      through a traditional interspecific introgression strategy. We developed one set
      of chromosome segment introgression lines (CSILs), where TM-1, the genetic
      standard in G. hirsutum, was used as the recipient parent and the long staple
      cotton G. barbadense cv. Hai7124 was used as the donor parent by molecular marker
      assisted selection (MAS). Among them, four CSILs, IL040-A4-1, IL080-D6-1, IL088
      A7-3 and IL019-A2-6, found to be associated with superior fiber qualities
      including fiber length, strength and fineness QTL in Xinjiang were selected and
      backcrossed, and transferred these QTLs into three commercial Upland cotton
      cultivars such as Xinluzao (XLZ) 26, 41 and 42 grown in Xinjiang. By backcrossing
      and self-pollinating twice, five improved lines (3262-4, 3389-2, 3326-3, 3380-4
      and 3426-5) were developed by MAS of background and introgressed segments. In
      diverse field trials, these QTLs consistently and significantly offered additive
      effects on the target phenotype. Furthermore, we also pyramided two segments from
      different CSILs (IL080-D6-1 and IL019-A2-6) into cultivar 0768 to accelerate
      breeding process purposefully with MAS. The improved lines pyramided by these two
      introgressed segments showed significant additive epistatic effects in four
      separate field trials. No significant alteration in yield components was observed
      in these modified lines. In summary, we first report that these CSILs have great
      potential to improve fiber qualities in Upland cotton MAS breeding programs.

PMID- 24306320
TI  - Genetic analysis and molecular mapping of crown rust resistance in common wheat.
AB  - This is the first report on genetic analysis and genome mapping of major dominant
      genes for near non-host resistance to barley crown rust ( Puccinia coronata var.
      hordei ) in common wheat. Barley crown rust, caused by Puccinia coronata var.
      hordei, primarily occurs on barley (Hordeum vulgare L.) in the Great Plain
      regions of the United States. However, a few genotypes of common wheat (Triticum
      aestivum L.) were susceptible to this pathogen among 750 wheat accessions
      evaluated. To investigate the genetics of crown rust resistance in wheat, a
      susceptible winter wheat accession PI 350005 was used in crosses with two
      resistant wheat varieties, Chinese Spring and Chris. Analysis of F1 plants and F2
      populations from these two crosses indicated that crown rust resistance is
      controlled by one and two dominant genes in Chris and Chinese Spring,
      respectively. To determine the chromosome location of the resistance gene Cr1 in
      Chris, a set of 21 monosomic lines derived from Chris was used as female parents
      to cross with a susceptible spring type selection (SSTS35) derived from the PI
      350005/Chris cross. Monosomic analysis indicated that Cr1 is located on
      chromosome 5D in Chris and one of the crown rust resistance genes is located on
      chromosome 2D in Chinese Spring. The other gene in Chinese Spring is not on 5D
      and thus is different from Cr1. Molecular linkage analysis and QTL mapping using
      a population of 136 doubled haploid lines derived from Chris/PI 350005 further
      positioned Cr1 between SSR markers Xwmc41-2 and Xgdm63 located on the long arm of
      chromosome 5D. Our study suggests that near non-host resistance to crown rust in
      these different common wheat genotypes is simply inherited.

PMID- 24306321
TI  - Accuracy of indirect estimation of power output from uphill performance in
      cycling.
AB  - PURPOSE: To use measurement by cycling power meters (Pmes) to evaluate the
      accuracy of commonly used models for estimating uphill cycling power (Pest).
      Experiments were designed to explore the influence of wind speed and steepness of
      climb on accuracy of Pest. The authors hypothesized that the random error in Pest
      would be largely influenced by the windy conditions, the bias would be diminished
      in steeper climbs, and windy conditions would induce larger bias in Pest.
      METHODS: Sixteen well-trained cyclists performed 15 uphill-cycling trials (range:
      length 1.3-6.3 km, slope 4.4-10.7%) in a random order. Trials included different
      riding position in a group (lead or follow) and different wind speeds. Pmes was
      quantified using a power meter, and Pest was calculated with a methodology used
      by journalists reporting on the Tour de France. RESULTS: Overall, the difference
      between Pmes and Pest was -0.95% (95%CI: -10.4%, +8.5%) for all trials and 0.24%
      (-6.1%, +6.6%) in conditions without wind (<2 m/s). The relationship between
      percent slope and the error between Pest and Pmes were considered trivial.
      CONCLUSIONS: Aerodynamic drag (affected by wind velocity and orientation, frontal
      area, drafting, and speed) is the most confounding factor. The mean estimated
      values are close to the power-output values measured by power meters, but the
      random error is between +/-6% and +/-10%. Moreover, at the power outputs (>400 W)
      produced by professional riders, this error is likely to be higher. This
      observation calls into question the validity of releasing individual values
      without reporting the range of random errors.

PMID- 24306322
TI  - Closed-loop systems and automation in the era of patients safety and
      perioperative medicine.

PMID- 24306323
TI  - Monitoring of intense neuromuscular blockade in a pig model.
AB  - Intense neuromuscular blockade (NMB) measured by post tetanic count (PTC) was
      monitored, reversed and verified in this pig model. In a cross-over assessor
      blinded design six pigs were randomized to either no NMB followed by intense NMB,
      or intense NMB followed by no NMB. Neuromuscular measurements were performed with
      acceleromyography [train-of-four (TOF) Watch SX]. In all pigs, the response to
      TOF nerve stimulation was stable and intense NMB (PTC 0-1) was established with
      rocuronium 3 mg/kg. For reversal, the pigs received sugammadex 20-35 mg/kg and
      returned to TOF-ratio above 0.90 within 2.15 min after injection. We established
      a pig model for monitoring intense NMB with surface stimulation electrodes and
      acceleromyography. We verified total relaxation of the diaphragm and the
      abdominal muscles at the PTC 0-1 by suction test and with surface
      electromyography. This pig model is suitable for studies with experimental
      abdominal surgery with monitoring of intense NMB, and where relaxation of the
      diaphragm and the abdominal muscles are required. 

PMID- 24306324
TI  - Ozakia, a new genus of winged fruit shared between the Miocene of Japan and
      western North America.
AB  - A new genus is recognized based on winged fruits with a single species shared
      between the Miocene of southwestern Honshu, Japan, and the Miocene of Oregon and
      Idaho, USA. Calyces of Ozakia emryi gen. et sp. n. were formerly attributed to
      Heptacodium (Caprifoliaceae) and Amelanchier (Rosaceae); however, newly recovered
      specimens reveal additional characters that contradict these assignments. The
      pedicellate fruits are obovate, tapering basally and truncate apically, with
      about 10 longitudinal ribs, a prominent epigynous synsepalous calyx of five
      lobes, each with a midvein and a pair of weaker, ascending intramarginal primary
      veins. The single style has a capitate stigma. Ozakia is considered to represent
      an extinct eudicot genus, the familial affinities of which remain uncertain. The
      eastern Asian-western North American disjunction of Ozakia occurrences suggests
      that this plant traversed the Beringia land bridge during or prior to the Middle
      Miocene. Relatively few extinct angiosperm genera are known as late as the
      Miocene. 

PMID- 24306325
TI  - Hepatitis B virus and hepatitis D virus in blood donors from Argentina:
      circulation of HBsAg and reverse transcriptase mutants.
AB  - In Argentina, current procedures to ensure the safety of the blood supply for
      transfusion include the serologic detection of specific blood-borne infections.
      The aim of this study was to evaluate the prevalence and the genetic diversity of
      hepatitis B virus (HBV) and hepatitis D virus (HDV) in blood donor populations
      from two distantly located Argentine regions. Data from 56,983 blood donations
      from the Favaloro Foundation, in the city of Buenos Aires (Central Region), and
      the Central Blood Bank of Misiones Province (Northeast Region) were analyzed.
      Samples that were reactive for HBsAg were analyzed for HBV-DNA characterization
      and HDV serological and molecular analysis. The HBV prevalence was 0.12 % for
      HBsAg and 1.68 % for anti-HBc antibodies in Buenos Aires, and 0.73 % and 8.55 %,
      respectively, in Misiones. Seventy-seven HBsAg-reactive samples were analyzed by
      polymerase chain reaction for HBV-DNA. Subgenotypes A2, B2, C2, F1b and F4
      (Buenos Aires) and F1b and D3 (Misiones) were detected. Several mutations within
      the major hydrophilic region of HBsAg, the reverse transcriptase, the basal core
      promoter, and the precore/core were detected. HDV genotype 1 was identified in
      Buenos Aires. This study confirms the circulation of several HBV subgenotypes, as
      well as known and newly identified variants, and the presence of HDV1 in this
      population. A thorough investigation has to be carried out to evaluate the
      clinical importance of some of the documented mutations as well as those detected
      in the HDV1 case.

PMID- 24306326
TI  - Critical evaluation of human oral bioavailability for pharmaceutical drugs by
      using various cheminformatics approaches.
AB  - PURPOSE: Oral bioavailability (%F) is a key factor that determines the fate of a
      new drug in clinical trials. Traditionally, %F is measured using costly and time
      consuming experimental tests. Developing computational models to evaluate the %F
      of new drugs before they are synthesized would be beneficial in the drug
      discovery process. METHODS: We employed Combinatorial Quantitative Structure
      Activity Relationship approach to develop several computational %F models. We
      compiled a %F dataset of 995 drugs from public sources. After generating chemical
      descriptors for each compound, we used random forest, support vector machine, k
      nearest neighbor, and CASE Ultra to develop the relevant QSAR models. The
      resulting models were validated using five-fold cross-validation. RESULTS: The
      external predictivity of %F values was poor (R(2) = 0.28, n = 995, MAE = 24), but
      was improved (R(2) = 0.40, n = 362, MAE = 21) by filtering unreliable predictions
      that had a high probability of interacting with MDR1 and MRP2 transporters.
      Furthermore, classifying the compounds according to the %F values (%F < 50% as
      "low", %F >= 50% as 'high") and developing category QSAR models resulted in an
      external accuracy of 76%. CONCLUSIONS: In this study, we developed predictive %F
      QSAR models that could be used to evaluate new drug compounds, and integrating
      drug-transporter interactions data greatly benefits the resulting models.

PMID- 24306327
TI  - Pharmacological characterization of 7-(4-(Piperazin-1-yl)) ciprofloxacin
      derivatives: antibacterial activity, cellular accumulation, susceptibility to
      efflux transporters, and intracellular activity.
AB  - PURPOSE: To evaluate pharmacological properties (antibacterial activity;
      accumulation in phagocytic cells; activity against intracellular bacteria;
      susceptibility to fluoroquinolone efflux transporters) of ciprofloxacin
      derivatives modified at C-7 of the piperazine ring. METHODS: N-acetyl- (1), N
      benzoyl- (2), N-ethyl- (3), and N-benzyl- (4) ciprofloxacin were synthesized.
      MICs against Escherichia coli and Staphylococcus aureus were determined following
      CLSI guidelines. Cellular accumulation, subcellular distribution, and
      intracellular activity (towards S. aureus and Listeria monocytogenes) were
      determined in J774 mouse macrophages. Efflux in bacteria (NorA [S. aureus], Lde
      [L. monocytogenes]) and in macrophages (Mrp4) was assessed using the
      corresponding inhibitors reserpine and gemfibrozil, respectively. RESULTS: All
      derivatives were active, though less than ciprofloxacin. 2 and 3 accumulated 2-3
      fold more than ciprofloxacin in mouse macrophages but remained substrates for
      efflux by Mrp4. 4 was insensitive to NorA and Lde, accumulated approx 50-fold
      more than ciprofloxacin in macrophages, was barely affected by Mrp4, localized in
      the soluble fraction of cells, and was equipotent to ciprofloxacin against
      intracellular bacteria. CONCLUSIONS: Benzyl substitution at C7 markedly affects
      the pharmacological profile of ciprofloxacin with respect to recognition by
      efflux transporters and cellular accumulation. N-benzyl-ciprofloxacin may serve
      as basis for designing molecules with higher intrinsic activity while remaining
      poorly susceptible to efflux.

PMID- 24306328
TI  - Occurrence of venlafaxine residues and its metabolites in marine mussels at trace
      levels: development of analytical method and a monitoring program.
AB  - Coastal areas are subject to growing pressures and impacts because of the
      increase in human activities. Lipophilic organic contaminants, such as polycyclic
      aromatic hydrocarbons (PAHs) or polychlorinated biphenyls (PCBs), have been
      monitored for decades within monitoring programs. However, until now, little
      information on the detection of so-called "emerging contaminants" such as
      hydrophilic organic compounds in the marine environment and no data on its
      metabolites or transformation products in marine organisms is available. In this
      report, a sensitive analytical methodology for identification and confirmation of
      venlafaxine (VEN) residues and five of its main metabolites in the marine mussels
      Mytilus galloprovincialis was validated. The sample preparation procedure was
      based on the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) approach.
      An analytical method was developed to quantify these compounds at trace levels by
      liquid chromatography coupled to high-resolution mass spectrometry. The method
      was then applied to marine mussels collected from the Mediterranean Sea in
      southeastern France. Residues of the antidepressant VEN were occasionally
      detected at ng/g dw level. In addition, the approach allowed us to identify
      several transformation products in the analyzed samples. N-desmethylvenlafaxine
      (NDV) was the most frequently detected metabolite followed by N,O-di
      desmethylvenlafaxine (NODDV). 

PMID- 24306329
TI  - Application of response function methodology for the simultaneous determination
      of potential fragrance allergens and preservatives in personal care products
      using micellar electrokinetic chromatography.
AB  - A micellar electrokinetic chromatography method was developed for determination
      of 15 suspected fragrance allergens and preservatives. The target compounds are
      widely used as ingredients in many personal care products, and all of them are
      included in the European Regulation concerning cosmetic products. The method was
      optimized by using a central composite experimental design and response surface
      methodology. A modified chromatographic response function was defined to weigh
      the terms in the response function adequately. After optimization of experimental
      conditions, a background electrolyte of 100 mM sodium dodecyl sulphate and 24 mM
      sodium tetraborate and pH 9.0 was selected for the separation of the analytes.
      The developed methodology was evaluated in terms of linearity, limits of
      detection and quantification, precision and accuracy, showing appropriate values
      (i.e., R (2) = >=0.99 and accuracy of 89-115 %). Finally, applicability of the
      micellar electrokinetic chromatography method was assessed by successfully
      quantifying fragrance allergens and preservatives in commercial personal care
      products. The most commonly found analyte was linalool (48.3 % of samples)
      followed by benzoic acid (37.6 %). All samples contained at least one of the
      target compounds, thus confirming the ubiquity of fragrance allergens and
      preservatives in personal care products. 

PMID- 24306330
TI  - Determination of urine caffeine and its metabolites by use of high-performance
      liquid chromatography-tandem mass spectrometry: estimating dietary caffeine
      exposure and metabolic phenotyping in population studies.
AB  - We have developed and validated a high-performance liquid chromatography-tandem
      mass spectrometric (LC-MS/MS) method for determining urine caffeine and 14
      caffeine metabolites suitable for estimating caffeine exposure and metabolic
      phenotyping in population studies. Sample preparation consisted solely of a
      series of simple reagent treatments at room temperature. Stable isotope-labeled
      analogs were used as internal standards for all analytes. We developed rapid LC
      MS/MS separations for both positive and negative ion mode electrospray
      ionizations to maximize measurement sensitivity. Limits of detection were 0.05
      0.1 MUmol/L depending on the analytes. Method imprecision, based on total
      coefficients of variation, was generally <7 % when analyte concentration was >1
      MUmol/L. Analyte recoveries were typically within 10 % of being quantitative (100
      %), and good agreement was observed among analytes measured across different
      MS/MS transitions. We applied this method to the analysis of a convenience set of
      human urine samples (n = 115) and were able to detect a majority of the analytes
      in >=99 % of samples as well as calculate caffeine metabolite phenotyping ratios
      for cytochrome P450 1A2 and N-acetyltransferase 2. Whereas existing LC-MS/MS
      methods are limited in number of caffeine metabolites for which they are
      validated, or are designed for studies in which purposely elevated caffeine
      levels are expected, our method is the first of its kind designed specifically
      for the rapid, sensitive, accurate, and precise measurement of urine caffeine and
      caffeine metabolites at concentrations relevant to population studies. 

PMID- 24306331
TI  - High-resolution time-of-flight mass spectrometry fingerprinting of metabolites
      from cecum and distal colon contents of rats fed resistant starch.
AB  - Time-of-flight mass spectrometry along with statistical analysis was utilized to
      study metabolic profiles among rats fed resistant starch (RS) diets. Fischer 344
      rats were fed four starch diets consisting of 55 % (w/w, dbs) starch. A control
      starch diet consisting of corn starch was compared against three RS diets. The RS
      diets were high-amylose corn starch (HA7), HA7 chemically modified with octenyl
      succinic anhydride, and stearic-acid-complexed HA7 starch. A subgroup received
      antibiotic treatment to determine if perturbations in the gut microbiome were
      long lasting. A second subgroup was treated with azoxymethane (AOM), a
      carcinogen. At the end of the 8-week study, cecal and distal colon content
      samples were collected from the sacrificed rats. Metabolites were extracted from
      cecal and distal colon samples into acetonitrile. The extracts were then analyzed
      on an accurate-mass time-of-flight mass spectrometer to obtain their metabolic
      profile. The data were analyzed using partial least-squares discriminant analysis
      (PLS-DA). The PLS-DA analysis utilized a training set and verification set to
      classify samples within diet and treatment groups. PLS-DA could reliably
      differentiate the diet treatments for both cecal and distal colon samples. The
      PLS-DA analyses of the antibiotic and no antibiotic-treated subgroups were well
      classified for cecal samples and modestly separated for distal colon samples. PLS
      DA analysis had limited success separating distal colon samples for rats given
      AOM from those not treated; the cecal samples from AOM had very poor
      classification. Mass spectrometry profiling coupled with PLS-DA can readily
      classify metabolite differences among rats given RS diets. 

PMID- 24306332
TI  - Helping (some) SSDI beneficiaries with severe mental illness return to work.

PMID- 24306333
TI  - Looking schizophrenia in the eye.

PMID- 24306334
TI  - Reassessing the safety of varenicline.

PMID- 24306335
TI  - 2013 in review.

PMID- 24306336
TI  - What's next for somatic symptom disorder?

PMID- 24306337
TI  - Where all and nothing is about mental health: beyond posttraumatic stress
      disorder for displaced Syrians.

PMID- 24306338
TI  - Postanesthesia persistent amnesia in a patient with a prior history of
      dissociative fugue state: the case for the two-hit hypothesis.

PMID- 24306339
TI  - Partners at the "interface".

PMID- 24306340
TI  - Drug-induced long QT in adult psychiatric inpatients: the 5-year cross-sectional
      ECG Screening Outcome in Psychiatry study.
AB  - OBJECTIVE: The authors aimed to determine the prevalence of drug-induced long QT
      at admission to a public psychiatric hospital and to document the associated
      factors using a cross-sectional approach. METHOD: All ECG recordings over a 5
      year period were reviewed for drug-induced long QT (heart-rate corrected QT >=500
      ms and certain or probable drug imputability) and associated conditions. Patients
      with drug-induced long QT (N=62) were compared with a sample of patients with
      normal ECG (N=143). RESULTS: Among 6,790 inpatients, 27.3% had abnormal ECG, 1.6%
      had long QT, and 0.9% qualified as drug-induced long QT case subjects. Sudden
      cardiac death was recorded in five patients, and torsade de pointes was recorded
      in seven other patients. Relative to comparison subjects, patients with drug
      induced long QT had significantly higher frequencies of hypokalemia, hepatitis C
      virus (HCV) infection, HIV infection, and abnormal T wave morphology.
      Haloperidol, sertindole, clotiapine, phenothiazines, fluoxetine, citalopram
      (including escitalopram), and methadone were significantly more frequent in
      patients with drug-induced long QT. After adjustment for hypokalemia, HCV
      infection, HIV infection, and abnormal T wave morphology, the effects of
      haloperidol, clotiapine, phenothiazines, and citalopram (including escitalopram)
      remained statistically significant. Receiver operating characteristic curve
      analysis based on the number of endorsed factors per patient indicated that 85.5%
      of drug-induced long QT patients had two or more factors, whereas 81.1% of
      patients with normal ECG had fewer than two factors. CONCLUSIONS: Drug-induced
      long QT and arrhythmia propensity substantially increase when specific
      psychotropic drugs are administered to patients with hypokalemia, abnormal T wave
      morphology, HCV infection, and HIV infection.

PMID- 24306341
TI  - Altered insula response to sweet taste processing in recovered anorexia and
      bulimia nervosa: a matter of disgust sensitivity?

PMID- 24306342
TI  - Response to Vicario.

PMID- 24306343
TI  - Prenatal genetic testing with chromosomal microarray analysis identifies major
      risk variants for schizophrenia and other later-onset disorders.

PMID- 24306344
TI  - ECT for developmental disability and severe mental illness.

PMID- 24306352
TI  - Different non-host resistance responses of two rice subspecies, japonica and
      indica, to Puccinia striiformis f. sp. tritici.
AB  - KEY MESSAGE: Japonica and indica have different non-host resistance (NHR)
      abilities to Puccinia striiformis f. sp. tritici ( Pst ), and hydrogen peroxide
      (H 2 O 2 ) has a positive function in NHR to japonica against Pst. ABSTRACT: Non
      host interactions between Puccinia striiformis f. sp. tritici (Pst) and two rice
      subspecies were characterized using 23 rice varieties, including 11 japonica and
      12 indica. Results showed that the infected fungal structures were easily
      produced in the leaves of indica, whereas only several substomatal vesicles and
      primary infection hyphae were observed in the leaves of japonica. This result
      indicated that indica is less resistant or more susceptible to Pst than japonica.
      Hydrogen peroxide accumulated in the initial phase of japonica-Pst interaction
      but not in indica-Pst interaction. A set of reactive oxygen species (ROS)-related
      genes was also induced in response to Pst infection, suggesting that ROS
      activation is one of the major mechanisms of non-host resistance of rice to Pst.

PMID- 24306353
TI  - cGMP and ethylene are involved in maintaining ion homeostasis under salt stress
      in Arabidopsis roots.
AB  - KEY MESSAGE: cGMP promotes ethylene production and enhances the perception of
      ethylene. Endogenous ethylene or cGMP accumulation maintains ion homeostasis to
      enhancing salt resistance. etr1 - 3 is insensitive to cGMP under salt stress.
      ABSTRACT: In the present study, we presented a signaling network involving
      ethylene and cGMP in salt resistance pathway of Arabidopsis roots. Results showed
      that the ethylene-insensitive mutant etr1-3 was more sensitive to salt stress
      than the wild type (WT). etr1-3 displayed a greater electrolyte leakage,
      thiobarbituric acid reactive substances and Na(+)/K(+) ratio, but a lower plasma
      membrane (PM) H(+)-ATPase activity compared to WT under the different NaCl
      contents. Application of 1-aminocyclopropane-1-carboxylic acid (ACC, an ethylene
      precursor) or 8-Br-cGMP (the cGMP analog) alleviated NaCl-induced injury by
      maintaining a lower Na(+)/K(+) ratio and increasing PM H(+)-ATPase activity in
      WT, but not in etr1-3. Roots treated with 8-Br-cGMP could promote ethylene
      production and enhance the expression of ACC synthase gene in WT. In addition,
      the 8-Br-cGMP action in NaCl stress was inhibited by aminooxyacetic acid (an
      inhibitor of ethylene biosynthesis), but 6-Anilino-5,8-quinolinedione (Ly83583, a
      guanylate cyclase inhibitor) could not affect ACC action in WT. These results
      suggest that ethylene functions as a downstream signal of cGMP that stimulates
      the PM H(+)-ATPase activity, which finally results in regulating ion homeostasis
      in Arabidopsis tolerance to salt. Moreover, cGMP enhanced the perception of
      ethylene in Arabidopsis under salt stress, which reversed the salt-induced
      increase of ETR1 and increased ERF1 at the transcript levels in WT. In a word,
      cGMP modulates salt resistance pathway of ethylene through regulating
      biosynthesis and perception of ethylene in Arabidopsis roots.

PMID- 24306355
TI  - Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune
      diseases in Denmark 1989-2008.
AB  - Autoimmune diseases have been little studied in gay men and lesbians. We followed
      4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47
      autoimmune diseases in the National Patient Registry between 1989 and 2008.
      Poisson regression analyses provided first hospitalization rate ratios (RRs)
      comparing rates between SSM individuals and persons in other marital status
      categories. SSM individuals experienced no unusual overall risk of autoimmune
      diseases. However, the risk of autoimmune thyroid dysfunction was increased,
      notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval
      (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01).
      There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95%
      CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36),
      rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis
      (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR =
      7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6),
      while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39
      0.99). The excess of psoriasis was restricted to same-sex married men with
      HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease
      occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR
      = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same
      sex marriage face no unusual overall risk of autoimmune diseases. However, the
      observed increased risk of thyroid dysfunction in these lesbians and gay men
      deserves further study.

PMID- 24306356
TI  - Development of interest and enjoyment in adolescence. Part I. Attentional
      capacities.
AB  - The first part of this two-part article argues that significant changes in both
      the capacity and the content of attention emerge in adolescence. Part I reviews
      evidence from behavioral and biological studies that the capacity for interested
      attention develops from late childhood into adolescence. 

PMID- 24306357
TI  - Development of interest and enjoyment in adolescence. Part II. Boredom and
      psychopathology.
AB  - Significant changes in both the capacity and the content of attention emerge
      during adolescence. Part II of this two-part article argues that a central task
      of adolescence is to utilize increased information-processing capacities in order
      to develop attentional habits which shape interests, provide enjoyment, and avoid
      boredom. Reports of chronic boredom or of extreme efforts to escape from boredom
      during adolescence may signify substantial difficulty in forming the attentional
      habits required for developing a separate identity. When adolescents are bored,
      they may resort to habits of attention and enjoyment which have deleterious
      personal, social, and ecological consequences. Further study of attention in
      adolescence may help to explore preventive educational approaches to the problem
      of boredom and of "pathological" solutions to boredom. 

PMID- 24306358
TI  - The nature and importance of attachment relationships to parents and peers during
      adolescence.
AB  - The nature and quality of adolescents' attachments to peers and parents were
      assessed with the newly developed Inventory of Adolescent Attachments. The
      relative influence on measures of self-esteem and life satisfaction of relations
      with peers and with parents was then investigated in a hierarchical regression
      model. The sample consisted of 213 adolescents ranging from 12 to 19 years of
      age. Two hypotheses were tested: (1) The quality of perceived attachments both to
      parents and peers would be related to well-being, and (2) the quality of parental
      relationships would be a more powerful predictor of well-being than would the
      quality of peer relationships. Confirming the study's hypotheses, the perceived
      quality of the adolescents' relationships to both peers and parents, their
      frequency of utilization of peers, and their degree of negative life change were
      significantly related to both measures of well-being. The quality of attachment
      to parents was significantly more powerful than that to peers in predicting well
      being. In addition, quality of attachment to parents showed a moderating effect
      under conditions of high life stress on the measures of self-esteem. The study
      suggests that it is useful to consider the quality of attachments to significant
      others as an important variable throughout the life span. 

PMID- 24306359
TI  - The relative importance of identity status interview components.
AB  - Eighty college males were given an expanded identity status interview which
      included two new interpersonal-sexual areas, "attitudes towards sexual
      expression" and "sex-role beliefs." The relative contribution of the new content
      areas as well as of the standard three areas (occupation, religion, and politics)
      to overall identity status was assessed by noting the extent of correspondence.
      Identity status in each content area was also compared with performance on the
      dependent variable of cognitive complexity. Ideology contributed more than
      occupation both to overall status rating, as well as to discrimination on the
      dependent variable. Results on the two new areas supported the view that
      interpersonal-sexual concerns are important for men's identity development as
      well as for women's. The finding that all interview areas corresponded well with
      overall identity status and discriminated significantly on the dependent measure
      leads to the suggestion that the process variables of crisis and commitment may
      so overshadow a particular content area that any content of personal relevance
      for the late adolescent might be used in investigating ego identity development. 

PMID- 24306360
TI  - Career development of adolescents: An ecological perspective.
AB  - Bronfenbrenner's ecological model of human development is used as a framework for
      examining the research on the career development of adolescents. The examination
      of the four contexts - the microsystem, the mesosystem, the exosystem, and the
      macrosystem - provides an additionalperspective to the ontogenic (individual)
      approach that has predominated the research literature in this field. Among the
      four contexts examined, some research on the influence of microsystem, including
      family, school,peer group, and workplace is identified. The amount of
      developmentally based research drops off quickly for the other systems, although
      there are other pertinent research and social issues for each system. Research
      and intervention implications of this perspective are indicated. 

PMID- 24306361
TI  - An exploratory study of dominance interactions among adolescent females at a
      summer camp.
AB  - One bunk of eight 16- to 17-year old females was studied over a four-week camping
      session. Instances of dyadic dominance behaviors between group members were
      recorded in three settings. Although participants formed a cohesive group
      dominance structure that remained relatively stable throughout the camp session,
      the structure was not rigid or hierarchical. A new term, "cohesive dyarchy," was
      coined to describe intracabin dominance relations. In contrast to many studies of
      adolescent females, popularity with boys and physical attractiveness were not
      found to be major predictors of dominance status. A variety of personality traits
      emphasizing interpersonal skills, athletic ability, and self-reported self-esteem
      predicted dominance status. Implications of these findings in terms of female
      adolescent development and future research are discussed. 

PMID- 24306362
TI  - The effects of assertive training on the performance self-esteem of adolescent
      girls.
AB  - Assertiveness training was provided for 148 girls in 10 high school business and
      homemaking classes in six senior high schools. Training sessions were co-led by
      an experienced leader and the students' own high school teacher. Significant
      changes in performance self-esteem scores were found between pretesting and a
      three-month follow-up (p<0.001) for the 103 subjects available at follow-up; low
      self-esteem subjects showed greater increases than high self-esteem subjects
      (p<0.001). Changes in self-esteem were related to the girls' perceptions of
      teacher reactions to their assertive behavior (p<0.01). 

PMID- 24306364
TI  - "[No] doctor but my master": Health reform and antislavery rhetoric in Harriet
      Jacobs's Incidents in the life of a slave girl.
AB  - This essay examines Harriet Jacobs's Incidents in the Life of a Slave Girl (1861)
      in light of new archival findings on the medical practices of Dr. James Norcom
      (Dr. Flint in the narrative). While critics have sharply defined the feminist
      politics of Jacobs's sexual victimization and resistance, they have overlooked
      her medical experience in slavery and her participation in reform after escape. I
      argue that Jacobs uses the rhetoric of a woman-led health reform movement
      underway during the 1850s to persuade her readers to end slavery. This essay
      reconstructs both contexts, revealing that Jacobs links enslaved women's physical
      and sexual vulnerability with her female readers' fears of male doctors' threats
      to modesty and of their standard bleed-and-purge treatments. Jacobs illustrates
      that slavery damages women's health as much as heroic medicine, and thus merits
      the political activism of her readers. Specifically, Jacobs dramatizes her
      conflicts with the rapacious physician-master at moments that are crucial to
      women's health: marriage, pregnancy, childbirth, and motherhood. Ultimately, this
      essay advances a new understanding of the role of health reform in social change:
      it galvanized other movements such as women's rights and abolition, particularly
      around issues of bodily autonomy for women and African Americans. 

PMID- 24306365
TI  - Changes in vitamin D and matrix metalloproteinase-9 in submariners during a
      submerged patrol.
AB  - OBJECTIVES: To quantify changes in vitamin D and matrix metalloproteinase-9
      (MMP9) in submariners over a single long patrol and compare the data to a group
      of non-deploying servicemen from their base port. METHODS: A prospective time
      series analysis was performed. Blood samples were taken from 49 submariners
      deploying on patrol and 43 shore-side controls from the base port (naval officers
      from base or non-deploying submariners), following a winter ashore at latitude 56
      degrees  north. Samples were drawn immediately before the submarine sailed, in
      January, and again in the final week of patrol 85 days later. Paired pre-patrol
      and late samples from each individual were assayed together and changes in
      vitamin D and MMP9 were assessed. RESULTS: Mean pre-patrol vitamin D
      concentrations were 58 and 49 nmol/L for the controls and submariners,
      respectively. Mean vitamin D concentrations increased in controls as expected
      (mean increase 12.6 nmol/L), but not in the submariners (mean decrease 1.6
      nmol/L). MMP9 levels were significantly higher in submariners pre-patrol, and
      increased significantly during the patrol. There was a significant inverse
      correlation between MMP9 and vitamin D levels (r=-0.41, p=0.01). CONCLUSIONS:
      This is the first study to quantify vitamin D and MMP levels in submariners.
      Circulating vitamin D concentrations on board were insufficient to prevent a rise
      in MMP. This has potential for adverse health effects and requires further study.

PMID- 24306366
TI  - pH and membrane-potential changes during glucose uptake inLemna gibba G1 and
      their response to light.
AB  - Extracellular pH was measured with a microelectrode positioned over the lower
      surface of singleLemna gibba plants. Upon addition of glucose, a transient
      extracellular alkalinization occurred. Saturated extracellular pH changes were
      observed with 5 mM glucose. Simultaneously, the membrane potential difference of 
      250 mV in the dark measured with intracellular glass micropipettes, trnasiently
      decreased by 105 mV. Uptake of [(14)C]glucose and extracellular alkalinization
      was enhanced by light whereas glucose-induced membrane-potential changes were
      reduced in the light and became even smaller with increasing the preillumination
      time. Glucose uptake was optimal at pH 6. The results are taken as further
      evidence in favor of H(+)-glucose cotransport inLemna. 

PMID- 24306367
TI  - Cell length, light and(14)C-labelled indol-3yl-acetic acid transport inPisum
      satisum L. andPhaseolus vulgaris L.
AB  - The putative auxin-transporting cells of the intact herbaceous dicotyledon are
      the young, differentiating vascular elements. The length of these cells was found
      to be considerably greater in dwarf (Meteor) than in tall (Alderman) varieties
      ofPisum sativum L., and to be greater in etiolated than in light-grown plants
      ofP. sativum cv Meteor andPhaseolus vulgaris L. cv Mexican Black. Under given
      light conditions during transport these large differences in cell length did not
      influence the shapes of the transport profiles or the velocity of transport
      of(14)C-labelled indol-3yl-acetic acid (IAA) applied to the apical bud. However,
      in both etiolated and light-grown bean and dwarf pea plants the velocity of
      transport in darkness was ca. 25% lower than that in light. Under the same
      conditions of transport velocities in bean were about twice those observed in the
      dwarf pea. Exposure to light during transport increased the rate of export
      of(14)C from the labelled shoot apex in green dwarf pea plants but not in
      etiolated plants. The light conditions to which the plants were exposed during
      growth and transport had little effect on the rates of uptake of IAA from the
      applied solutions. The results indicate that the velocity of auxin transport is
      independent of the frequency of cell-to-cell interfaces along the transport
      pathway and it is suggested that in intact plants auxin transport is entirely
      symplastic. 

PMID- 24306368
TI  - Action spectra for the light inhibition of flowering and its reversal inLemna
      paucicostata T-101.
AB  - Lemna paucicostata Hegelm. T-101, a short-day plant, flowers when plants
      preirradiated with red light (R) for 24 h are subjected to inductive darkness for
      72 h followed by two short-day cycles (6 h R+ 18 h dark). However, flowering is
      inhibited by blue-or far-red-light pulses applied at the beginning of the
      inductive dark period. These inhibitory light effects are fully reversible by a R
      pulse. The action spectra for the inhibitory light effect and for its reversal
      show that the light pulses act exclusively through phytochrome. It is concluded
      that a low level of Pfr at the beginning of the inductive dark period prevents
      flowering. 

PMID- 24306369
TI  - Anti-microtubular herbicides and fungicides affect Ca(2+) transport in plant
      mitochondria.
AB  - The herbicides amiprophosmethyl (APM) trifluralin, and oryzalin as well as the
      fungicides methylbenzimidazolyl carbamate (MBC), O-isopropyl N-phenyl carbamate
      (IPC), and chlorisopropyl N-phenyl carbamate (CIPC), which are known to cause the
      destruction of microtubules in vivo but do not interfere with tubulin
      polymerization in vitro, have been examined with respect to their ability to
      affect Ca(2+) transport in isolated cell organelles. In contrast to colchicine
      which has no effect on Ca(2+) transport in isolated mitochondrial and microsomal
      fractions, all of the substances investigated caused considerable reduction of
      ca(2+) net uptake into mitochondrial but not into microsomal fractions. This
      reduction has been shown to be due to an increase in passive Ca(2+) efflux. These
      results have been extrapolated to in vivo situations where they are postulated to
      act by raising cytoplasmic Ca(2+) levels. 

PMID- 24306370
TI  - Acid phosphatase activity in plastids (plastolysomes) of senescing embryo
      suspensor cells.
AB  - Autolysis of the suspensor, an embryonal haustorium, starts in the basal cells
      and proceeds in the direction of the embryo. InPhaseolus vulgaris, acid
      phosphatase activity is first found in transforming plastids, similar to the acid
      phosphatase activity inPh. coccineus [Nagl (1977) Z. Pflanzenphysiol.85, 45-51],
      although the ultrastructural details are different. InTropaeolum majus, autolysis
      begins in the most distal part of the suspensor, i.e., the chalazal or carpel
      haustorium. First the endoplasmic reticulum shows acid phosphatase activity, but
      neither the mitochondria, which undergo transformation similar to that observed
      in plastids ofPhaseolus, nor the leucoplasts show such activity. Later, however,
      the plastids exhibit low activity. Contrarily, the plastids in the suspensor
      cells adjacent to the embryo show increasing activity during senescence of the
      suspensor. During final autolysis, activity is found in all cytoplasmic
      membranes, while it is reduced in plastids. The visible ultrastructural
      transformations of various organelles into cytolysomes does not necessarily
      coincide with acid phosphatase activity. Our findings are a further indication of
      the high diversification and specialization of plastids during plant
      embryogenesis. 

PMID- 24306371
TI  - Binding of colchicine to a soluble fraction of carrot cells grown in suspension
      culture.
AB  - The binding of [(3)H]colchicine to soluble component prepared from carrot (Daucus
      carota L.) cells in suspension culture was assayed by the diethylaminoethyl(DEAE)
      cellulose powder method. The binding activity was very labile and the time course
      of the binding indicated that the colchicine-bound complex was also unstable. The
      reaction was enhanced by vinblastine but lumicolchicine had no effect. The
      optimum temperature for the reaction was 30 degrees  C, and the colchicine
      binding constant was calculated to be 3.5.10(4) l mol(-1) at 30 degrees  C. 

PMID- 24306372
TI  - Analysis of the regulation of adenosine 5'-phosphosulfate sulfotransferase
      activity inLemna minor L. using(15)N-density labeling.
AB  - The role of de novo synthesis in the regulation of adenosine 5'-phosphosulfate
      sulfotransferase activity by H2S inLemna minor L. was investigate using density
      labeling with(15)N applied as(15)NO 3 (-) in the culture medium. While adenosine
      5'-phosphosulfate sulfotransferase activity was rapidly reduced by H2S and
      rapidly recovered upon removal of H2S, O-acetyl-L-serine sulfhydrylase (EC
      4.2.99.8) did not show changes in extractable activity in response to H2S and
      could therefore be used as an internal marker enzyme for density labeling. The
      incorporation of(15)N into adenosine 5'-phosphosulfate sulfotransferase was
      strongly reduced upon transfer of plants into a H2S-containing atmosphere. Half
      maximal labeling was reached only after 70-80 h compared to 40-50 h in the
      control. After removal of H2S, adenosine 5'-phosphosulfate sulfotransferase
      activity increased to the initial level within 20 h, and the enzyme reached
      halfmaximal labeling after only 15 h. The time course of the density increase of
      O-acetyl-L-serine sulfhydrylase was not affected very significantly by H2S. These
      results provide evidence that de novo synthesis of enzyme protein is involved in
      the regulation of adenosine 5'-phosphosulfate sulfotransferase activity by H2S. 

PMID- 24306373
TI  - The endoplasmic reticulum of mung-bean cotyledons : Biosynthesis during seedling
      growth.
AB  - Germination and seedling growth of mungbean (Vigna radiata (L.) Wilczek) are
      accompanied by the incorporation of radioactive amino acids, glycerol, galactose,
      and glucosamine in an organelle fraction of the cotyledons which co-equilibrates
      with NADH-cytochrome-c-reductase activity at 1.13 g.cm(-3) on isopycnic gradients
      containing 1 mM EDTA. Up to 20% of the newly synthesized proteins accumulate in
      this organelle fraction. The organelle fraction has been identified as rough
      endoplasmic reticulum (ER) on the basis of its increased density (1.16 g.cm(-3))
      when 3 mM MgCl2 is included in all media. Seedling growth is also accompanied by
      a marked rise (more than 5-fold) in ER-associated NADH- and NADPH-cytochrome-c
      reductase activity, and by the incorporation of(59)Fe into ER-associated heme.
      Other manifestations of the reorganization of the ER in the cotyledons include a
      relative increase in membrane-associated RNA (from 12% of total RNA after 12 h of
      imbibition to 23% after 6 d of growth), and a change in the pattern of
      polypeptides associated with the ER. These results provide further evidence for
      the extensive reorganization of the ER of the cotyledons which accompanies
      seedling growth. The reorganization includes the simultaneous breakdown of the
      pre-existing tubular ER and the biosynthesis of new ER components. 

PMID- 24306374
TI  - Spiral growth in the radially-expanding piloboloid mutants ofPhycomyces
      blakesleeanus.
AB  - The growth zone of the sporangiophore of a piloboloid mutant,pil, ofPhycomyces
      expands radially at an increased rate until the growth zone becomes nearly
      spherical, in sharp contrast to that of the wild-type sporangiophore which
      exhibits longitudinal elongation only and is conical. The rotation of thepil
      sporangiophore reverses its direction from clockwise (CW) to counterclockwise
      (CCW) during the period of increased radial expansion, and the CCW rotation
      continues as long as does the radial expansion. The direction of rotation and the
      time of reversal are correlated with the relative rates of cell-wall expansion in
      the longitudinal and transverse directions. The CCW rotation of the
      sporangiophore of this mutant can be explained by the behavior of the
      microfibrils, as previously proposed to explain the rotation of the wild-type
      sporangiophore. 

PMID- 24306375
TI  - Nutritional regulation of organelle biogenesis inEuglena: Photo- and metabolite
      induction of mitochondria.
AB  - Exposure of dark-grown restingEuglena gracilis Klebs var.bacillaris Cori to
      light, ethanol, or malate produced an increase in the specific activity of
      fumarase (EC. 4.2.1.2) and succinate dehydrogenase (EC. 1.3.99.1) during the
      first 8-12 h of exposure to inducer, followed by a decrease in the specific
      activity of both mitochondrial enzymes between 12 and 72 h. The increased
      specific activity represented a net increase in the level of active enzyme, and
      it was dependent upon cytoplasmic protein synthesis. The photoinduction of
      fumarase required continuous illumination while the subsequent decrease in
      fumarase specific activity was independent of light. Light had little effect on
      the ethanol and malate induction of fumarase and succinate dehydrogenase. In the
      mutant W3BUL, which has no detectable protochlorophyll(ide) and chloroplast DNA,
      light induced both mitochondrial enzymes and the kinetics of enzyme induction
      were similar to the induction kinetics in wild-type cells. The induction of
      mitochondrial enzymes appears to be controlled by a non-chloroplast
      photoreceptor. Dark-grown resting cells of the plastidless mutant W10SmL have
      lost the ability to regulate fumarase levels. In this mutant, the specific
      activity of fumarase fluctuated and light had little effect on these
      fluctuations, indicating that fumarase synthesis was uncoupled from the
      nonchloroplast photoreceptor. Ethanol addition produced transient changes in
      fumarase specific activity in W10SmL indicating that in this mutant,
      mitochondrial enzymes are still inductible by metabolites. Fumarase synthesis in
      wild-type cells was not induced in the dark by levulinic acid, a chemical inducer
      of the breakdown ofEuglena storage carbohydrates. Taken together, our results
      indicate that the photoinduction of mitochondrial enzyme synthesis is not a
      result of the photoinduction of carbohydrate breakdown. The mechanisms by which
      light and organic carbon induce the synthesis ofEuglena mitochondria may differ. 

PMID- 24306376
TI  - Light inhibition of internode elongation in green plants : A kinetic study
      withVigna sinensis L.
AB  - The clongation of the first internode of fully greenVigna sinensis L. is
      inhibited by white light (W). This inhibition is fluence-rate dependent between 0
      and 70 Wm(-2). The kinetics of elongation rate in the light after darkness were
      investigated with linear displacement transducers. The internode elongation rate
      does not exhibit any endogenous rhythm. A rapid inhibition occurs during the
      first 2 or 3 h after the onset of light, and a second type of inhibition (slow
      reaction) increases from the beginning to the 8th hour of light. The rapid
      inhibition is not fluence-rate dependent between 20 and 70 Wm(-2), but the slow
      reaction is. There is no rapid inhibition in a low fluence rate white light to
      high fluence rate white light transition, only the slow reaction is observed. The
      responses to different wavebands, i.e., blue light (B), yellow and green light
      (YG), and red light (R), are the same for the two inhibition reactions. Each
      waveband used separately does not reproduce the full effect observed in W.
      Results show a stimulation with B, a greater inhibition activity with YG than
      with R, and a synergistic action of B and R which when given together lead to an
      inhibition similar to that obtained in W. Plants returned from the light to
      darkness progressively recover a high elongation rate without any latent period.
      The W light regulating internode elongation rate is mainly perceived by the
      growing internode itself. 

PMID- 24306377
TI  - Microtubules and coated vesicles in guard-cell protoplasts ofAllium cepa L.
AB  - Protoplasts were prepared from the guard cells ofA. cepa. Epidermal peels taken
      from expanding green leaves and largely free of mesophyll were treated with
      Cellulysin, and protoplasts were harvested after 18 h of digestion. That the
      protoplasts were derived from guard cells was ascertained from their
      characteristic vacuolar autofluorescence and from observations showing that all
      other epidermal cells are killed in the peeling procedure. The protoplasts proved
      to be a good system with which to view the cell cortex and inner surface of the
      plasmalemma. The lysis of cells adhering to polylysine-treated, Formvar-coated
      grids, followed by negative staining in uranyl acetate, showed that many
      microtubules normally present in ordered arrays in situ remain closely applied to
      the inner surface of the plasmalemma in protoplasts. In addition, numerous
      vesiculate elements including coated vesicles and/or pits are present amongst the
      microtubules. Similar vesicles are evident in thin sections of fixed, embedded
      guard cells and protoplasts. The significance of these structures in the cell
      cortex is discussed. 

PMID- 24306378
TI  - The induction of cytokinin habituation in primary pith explants of tobacco.
AB  - Pith parenchyma tissue ofNicotiana tabacum L. cv. "Havana 425" becomes cytokinin
      habituated when incubated at 35 degrees C on an auxin-containing medium. Under
      these conditions, habituated, hyperplastic nodules appear on the tissues. We used
      these nodules to estimate the incidence of habituation by a statistical method.
      The rate of habituation varied with the season. Tissue isolated from plants in
      the spring habituated approx. 7 times faster than did tissue isolated from plants
      in winter. The fact that the average rate, >4*10(-3) per cell generation, was 100
      1,000 times faster than the rate of somatic mutation inNicotiana species and
      depended on the physiological state of the tissue provides further evidence that
      habituation involves epigenetic changes rather than rare, random genetic
      mutations. We also found that kinetin (6-furfurylaminopurine) induced habituation
      and that the concentration required depended on the duration of cytokinin
      treatment. For long incubation times, approx. 6*10(-10) M kinetin, which is about
      1,000-fold lower than the concentration optimal for growth of cytokinin-requiring
      pith tissue, was sufficient to induce habituation. These results support the
      hypothesis that the habituated state is maintained by a positive feedback loop in
      which cytokinins either induce their own synthesis or inhibit their own
      degradation. 

PMID- 24306379
TI  - A reliable method for preparation and electron microscopic visualization of
      nucleosomes in higher plants.
AB  - An improved and reliable method is given for the preparation and electron
      microscopic visualization of nucleosomes in higher plants. The critical steps of
      the technique are indicated and enough details are given to allow for its use
      without any prior experience. 

PMID- 24306380
TI  - In vivo photoinactivation of ribulose bisphosphate carboxylase in the gas
      vacuolate cyanobacteriumMicrocystis aeruginosa.
AB  - Irradiation of buoyant, gas-vacuolate cells of the cyanobacteriumMicrocystis
      aeruginosa by 5.10(4) Wm(-2) of blue light for 1 h caused a 5% loss of
      extractable ribulose bisphosphate carboxylase activity compared to dark and red
      light controls. Ribulose bisphosphate carboxylase activity was unaffected by blue
      light in similar experiments conducted with cells containing collapsed gas
      vacuoles. 

PMID- 24306381
TI  - Induction of male flowers in a pistillate line ofRicinus communis L. by silver
      and cobalt ions.
AB  - Aqueous solutions of silver nitrate (10-100 MUg/plant) and cobalt chloride (125
      500 MUg/plant), injected into the main stem of plants of the pistillate cv. 240
      ofRicinus communis when the vegetative shoot apex was beginning to become
      reproductive, induced the formation of staminate (male) flowers with viable
      pollen in the normally strictly pistillate (female) terminal inflorescence, their
      number increasing with the dose of Ag(+) and Co(2+). No formation of bisexual
      flowers was noted. Female flowers pollinated with pollen from the induced male
      ones produced fruits and viable seeds. 

PMID- 24306382
TI  - Changes in chloraplast number during pea leaf development. An analysis of a
      protoplast population.

PMID- 24306383
TI  - Isolation of a recessive barley mutant resistant to S-(2-aminoethyl)L-cysteine.
AB  - S-(2-aminoethyl)L-cysteine (AEC) inhibits the growth of mature barley (Hordeum
      vulgare L vars. 'Bomi' and 'Maris Mink') embryos grown on sterile medium. This
      inhibition is relieved by lysine and, to a lesser extent, arginine and ornithine.
      In order to try and select plants which accumulate lysine, 8200 M2 embryos of
      sodium azide mutagenised barley were screened for growth in the presence of 0.25
      mM AEC. One line, R906 was selected for further characterisation. Progeny of the
      originally selected plant after selfing were all resistant to AEC. In a
      reciprocal cross with a sensitive barley the resistant trait was inherited as a
      single recessive nuclear gene which we designate aec-1. 

PMID- 24306384
TI  - Quantitative inheritance and barriers to crossability in Cicer arietinum L.
AB  - Three different diallel crosses were studied in Cicer arietinum; two of size 6*6,
      one within each of the two botanical groups 'macrosperma' and 'microsperma' of
      the cultivated subspecies, and one of 9*9 involving lines covering most of the
      morphological variation of chickpea. Barriers to crossability present neither a
      botanical nor a geographical pattern, being probably a direct consequence of
      interactions between genotypes. The genetic systems of twelve quantitative
      characters were analysed. Full dominance in a negative sense (small values
      dominant) is shown by leaflet length, width and shape index, rachis length,
      leaflet density on the rachis and pod length. Full dominance in a positive sense
      is shown by seeds per pod. Overdominance (in a positive sense) is evident for
      pods, seeds and yield per plant. Weak reciprocal differences were manifested by
      pod length, and pods, seeds and yield per plant. The system controlling number of
      leaflets per leaf is not clear. Dominance of 'primitive' over 'selected'
      characters seems to be the rule. As far as the environmental effects have
      permitted the analysis, no differences in genetic systems were observed between
      botanical groups. 

PMID- 24306385
TI  - On the prospects of using balanced sex-linked lethals for insect pest control.
AB  - A new method is suggested for controlling species of insect pests in which the
      female is heterogametic. This method, involving the use of balanced lethals on
      the Z chromosome, causes the death of females in the embryonic stage. The method
      has already been tested in practical sericulture for the production of entirely
      male progeny of the silkworm. The method requires the construction of two strains
      of the pest, one carrying two balanced nonallelic but closely located lethals on
      the Z chromosome, and another with two other pairs of lethals of the same type.
      In the hybrid progeny from the crosses between the two strains, 100% of the
      female embryos would die, thus making it possible to release only males without
      any laborious procedure for sex discrimination. In the progeny from the crosses
      between the released males and females from the natural population, again 100% of
      females would die, but the males would survive and when they mated - 62.5% of the
      female progeny would die. This rate would decline to 34.4 and 16.6% in the sons
      and grandsons respectively. The repeated release of hybrid males would lead to a
      progressive increase, with each successive generation, in the percentage of
      female mortality in the natural population until its total extinction. 

PMID- 24306386
TI  - S allele discrimination in styles of Petunia hybrida bearing stylar-conditioned
      pseudo-self-compatibility.
AB  - A cross between a 0% pseudo-self-compatible (PSC) plant (S3.3) and a 100% PSC
      plant (S1.1) yielded an F1 population which, when selfed, produced a high mean
      seed set which was not significantly different than that produced when the F1 was
      backcross pollinated by the 100% PSC parent. Backcross pollinating the F1 with
      the 0% PSC parent yielded no seed. No S3.3 plants were recovered in the F2
      populations, indicating that pollen tubes containing the S3 allele were inhibited
      during pollen tube growth of the selfed F1 plants. Apparently stylar-conditioned
      PSC does not remove all discriminatory power from these petunia styles. Crossing
      the F1 (S1.3) with an self-incompatible (SI) plant (S2.2) produced plants which
      were used for computation of a standard linkage test. An approximate map distance
      of 28 units was found between the S specificity locus and the major gene(s) which
      influenced its expression. Other generalized PSC modifying genes apparantly were
      not linked with the S locus. 

PMID- 24306387
TI  - Incompatibility alleles in Corylus avellana L. cultivars.
AB  - Pollen-stigma compatibility relationships are reported for 55 filbert cultivars
      (cvs) (Corylus avellana L.). A total of 11 S-alleles have been identified amongst
      36 cvs for which one or both S-alleles have been established. For the 20 cvs with
      only one known allele and the 17 for which neither allele have been identified
      further information is provided as to which alleles can be excluded as
      possibilities. 

PMID- 24306388
TI  - Correlations between various characters of inbred strains of corn and the
      relationship between inbred strains and their hybrids tested at three different
      ecological locations.
AB  - 1. The different reactions of inbred strains and hybrids often influence yield
      performance under different ecological conditions. Because of the negative
      correlation between length of vegetation period and yield of the hybrids (r=
      0.473) it was possible in some cases to obtain higher yields in a shorter
      vegetation period up to tasseling and silking. In kernel yield, the relationship
      between inbred strains and their hybrids was small. Here, specific combining
      ability is much more important, and length of vegetation period did not show any
      apparent direct influence. Only in cases of a combination of both high-yielding
      performance and appropriate day length and temperature could high yields be
      obtained under corresponding climatic conditions. 2. Dry matter content in
      kernels at harvest time was distinctly influenced by length of vegetation period
      (r=0.639 for inbred strains and r=0.767 for hybrids). Correlation between strains
      and hybrids in dry matter content of kernels was not very close (r=0.335). 3.
      Grain yield was much more influenced by the number of kernels per plant in inbred
      strains (r=0.572) than in hybrids (r=0.338), but there was no dependence of the
      number of kernels per plant on length of vegetation period. The number of kernels
      was much more influenced by the number of rows per ear (r=0.761 for inbred
      strains and 0.531 for hybrids), by diameter of ear (r= 0.672 and r=0.414) and by
      length of ear (r=0.684 and 0.657) respectively. For these characteristics the
      correlation between inbred strains and hybrids was distinct for length of ear
      (r=0.537) and number of kernels per plant (r=0.384) only. Some strains, however,
      did show a closer correlation in these characteristics. 4. Yield is influenced
      quite clearly by TKW as well (r=0.546 for inbred strains and 0.703 hybrids).
      There was no relationship between the other tested characters and TKW. The
      inheritance of these characters between inbred strains and hybrids was quite
      clear, especially for Cr Mi (r=0.808). 5. Cob percentage (in % d.m. of the whole
      ear) was only weakly inherited by some of the lines, for example, F 2. Between
      kernel yield and cob percentage, a negative correlation with r=-0.542 for the
      inbred strains and r=-0.307 for the hybrids could be found. 

PMID- 24306389
TI  - Strategies for radiology reporting and communication : part 4: quality assurance
      and education.

PMID- 24306391
TI  - Making your way as an academic paediatric trainee in the UK.
AB  - A career path in academic paediatric medicine is an extremely rewarding one, and
      while not traditionally considered an academic specialty, it offers a wealth of
      exciting research opportunities. Developing academic paediatrics is becoming
      increasingly important, as recently reviewed in the Royal College of Paediatrics
      and Child Health (RCPCH) Turning the Tide report, and developing future leaders
      in academic paediatrics is a key goal of the academic training pathways.
      Strategies are being implemented to ensure that the enthusiasm of academic
      trainees is maintained, and their development into future leaders is secured.

PMID- 24306390
TI  - Intensity of physical activity in the energy expenditure of older adults.
AB  - This study examined the intensity of activity contributing to physical activity
      energy expenditure in older adults. In 57 men and women aged >= 65, total energy
      expenditure (TEE) was measured using doubly labeled water and resting metabolic
      rate was measured using indirect calorimetry to calculate a physical activity
      index (PAI). Sedentary time and physical activity of light and moderate to
      vigorous (mod/vig) intensity was measured using an accelerometer. The subjects
      were 75 +/- 7 yrs (mean +/- SD) of age and 79% female. Subjects spent 66 +/- 8,
      25 +/- 5, and 9 +/- 4% of monitor wear time in sedentary, light, and mod/vig
      activity per day, respectively. In a mixture regression model, both light (beta =
      29.6 [15.6-43.6, 95% CI]), p < .001) and mod/vig intensity activity (beta = 28.7
      [7.4-50.0, 95% CI]), p = .01) were strongly associated with PAI, suggesting that
      both light and mod/vig intensity activities are major determinants of their
      physical activity energy expenditure. 

PMID- 24306392
TI  - Pulse oximetry in children.
AB  - Pulse oximetry is routinely used in hospitals in high-income settings, but its
      theoretical basis is often poorly understood. This paper summarises the
      physiological background, technological basis and limitations of pulse oximetry.

PMID- 24306393
TI  - Components of female sex pheromone of cocoa pod borer moth,Conopomorpha
      cramerella.
AB  - The cocoa pod borer,Conopomorpha cramerella (Snellen) (Lepidoptera:
      Gracillariidae), is the most serious pest of cocoa in Southeast Asia. Analyses of
      ovipositor washings and entrained volatiles from virgin female moths by gas
      chromatography (GC) linked to electroantennography (EAG), and comparison of EAG
      responses from the male moth to synthetic compounds indicated the presence of
      theE,Z,Z andE,E,Z isomers of 4,6,10-hexadecatrienyl acetate and the corresponding
      alcohols, and of hexadecyl alcohol. Amounts of pheromone produced were less than
      0.1 ng/female, and no peaks for the unsaturated components were observed on GC
      analysis. Extensive field testing of synthetic mixtures in Sabah, East Malaysia,
      showed that traps baited with a polyethylene vial impregnated with 1.2 mg of a
      mixture of the above five components in 40?60?4?6?10 ratio caught more maleC.
      cramerella moths than traps baited with a virgin female moth. 

PMID- 24306394
TI  - Sensory and behavioral effects of gossyplure alcohol on sex pheromone response of
      male pink bollworm moths,Pectinophora gossypiella.
AB  - (Z,Z)- and (Z,E)-7,11-hexadecadienol, reported to be pheromone precursors,
      interfere with the normal sequence of behavioral response of malePectinophora
      gossypiella to sex pheromone. The magnitude of the interference can be diminished
      with higher release rates of the sex pheromone. (Z,Z)-7,11-Hexadecadienol is more
      effective than itsZ,E isomer in eliciting the reduction in the behavioral
      response. Electroantennographic evidence suggests that each alcohol may be
      interfering more with receptor sites for the conformationally similar pheromone
      acetate than with receptor sites for the other pheromone isomer. Defining
      behavioral and physiological effects of pheromone analogs such as the alcohols of
      gossyplure may help to determine their potential for behavioral manipulations. 

PMID- 24306395
TI  - Behavioral responses of male and female Mexican fruit flies,Anastrepha ludens, to
      male-produced chemicals in laboratory experiments.
AB  - The behavioral responses of male and female Mexican fruit flies elicited by male
      abdominal extracts were measured in laboratory cages where pheromone was applied
      to the undersides of some leaves on a treated tree but to none of the leaves on a
      control tree. After arrival to the treated tree, females came directly to
      pheromone sources. Females on the treated tree visited leaves and fought other
      females at higher rates than on the control tree. Females stayed on treated
      leaves and trees longer than on control leaves and trees. In separate
      experiments, the number of males on pheromone-treated trees and leaves was higher
      than on controls, but other behavior was unchanged. The results indicate that the
      pheromone stimulates a complex of behavior involved in the mating ecology of the
      species. 

PMID- 24306396
TI  - Flavonoid pigments and wing color inMelanargia galathea.
AB  - Melanargia galathea L. from four different populations were classified into three
      categories, white, cream, and yellow, according to the background color of their
      wings. The flavonoid content of the wing and body tissues of butterflies in each
      of these categories was spectrophotometrically determined. A direct relationship
      was found between the wing background color and the flavonoid content of the
      wings; the greater the flavonoid content, the yellower the wings. Butterflies
      from the yellow category contained an average of 19.6 MUg flavone/mg wing tissue;
      those from the cream, an average of 14.1 MUg/mg tissue; and those from the white
      an average of 8.3 MUg/mg wing tissue. Flavonoids represent on average about 1.9%
      by weight of the yellow wings; 1.4% of the cream wings; and about 0.8% by weight
      of the white wings. The most frequently encountered wing background color in each
      of the populations examined was cream; far fewer individuals had white or yellow
      wings. Flavonoids were not evenly distributed in the wings ofM. galathea; greater
      quantities occur on the underside of the hindwings and front margins of the
      forewings, while the ocelli centers of the underside of the hindwings, and the
      inner margins on the upperside of the hindwings lack flavonoids. Furthermore,
      flavonoids were found in the white scales ofM. galathea but not in the black. The
      flavonoid content of the body ofM. galathea was found to be much lower than that
      of the wings. When expressed as a percentage of that in the wings, the flavonoid
      content of the body of both sexes was relatively constant; however, the flavonoid
      content of the female body represents on average about 59% of that in the wings,
      compared to about 20% in the male. Both the gross flavonoid content and the
      flavone concentration per milligram of tissue were found to be greater in female
      than male butterflies. Since the concentration of flavone per cm(2) of wing
      tissue was the same in both sexes, the greater flavonoid content of female than
      maleM. galathea has been attributed to the deposition of relatively large
      quantities in the reproductive tissues of the female. The possible role(s) of
      flavonoid pigments in wing coloration, in protecting vulnerable tissues from
      damaging ultraviolet radiation, in mate selection and/or sex recognition, in
      insect defense against vertebrate predators, and as antimicrobial agents inM.
      galathea has been discussed. 

PMID- 24306397
TI  - 2,6-Dichlorophenol in the tickRhipicephalus appendiculatus Neumann : A
      reappraisal.
AB  - Certain olfactory cells of maleRhipicephalus appendiculatus Neumann are known to
      be stimulated by 2,6-dichlorophenol.R. appendiculatus has been reexamined for the
      presence of 2,6-dichlorophenol, and it has been detected in both male and female
      adults. Unfed females contain 12 ng/ tick, declining to 2 ng/tick after six days
      of feeding, while unfed males contain 2 ng/tick, falling to 0 after feeding.
      Larval tick extracts which are also known to stimulate 2,6-dichlorophenol
      sensitive cells were examined and found to contain this phenol, whereasR.
      appendiculatus eggs did not contain this compound. 

PMID- 24306398
TI  - Inhibitory action of (4S,6S,7R)-isomer to pheromonal activity of serricornin,
      (4S,6S,7S)-7-Hydroxy-4,6-dimethyl-3-nonanone.
AB  - By adding the effects of a series of the stereoisomers to the pheromonal activity
      of serricornin, (4S,6S,7S)-7-hydroxy-4,6-dimethyl-3-nonanone, the sex pheromone
      of the cigarette beetleLasioderma serricorne (F.) was investigated. The
      experiments using synthetic enantiomeric mixtures and optically active
      stereoisomers showed that the (4S,6S,7R)-isomer inhibited significantly the
      pheromonal activity of serricornin. 

PMID- 24306399
TI  - Orientation of boll weevil,Anthonomus grandis boh. (Coleoptera: Curculionidae),
      to pheromone and volatile host compound in the laboratory.
AB  - Behavioral responses of male and female boll weevils to the aggregation
      pheromone, grandlure, and the major volatile of cotton, beta-bisabolol, were
      investigated using a new dual-choice olfactometer. Dosage-response experiments
      revealed both males and females to be attracted by the aggregation pheromone at
      the 1.0 MUg dosage. However, only males were attracted to beta-bisabolol (1.0
      MUg). Both sexes were repelled by the highest dosage ofbeta-bisabolol tested (10
      MUg). In preference experiment, males chose grandlure over beta-bisabolol, while
      both sexes chose the combination of grandlure + beta-bisabolol over beta
      bisabolol alone. There was some evidence for synergism between pheromone and
      plant odor for the females. The results correlate well with previous
      electrophysiological and behavioral experiments. 

PMID- 24306400
TI  - Urinary signaling pheromone and specific behavioral response in tree shrews
      (Tupaia belangeri) : I. Basic investigations for a bioassay.
AB  - As soon as they encounter the scent marks made by the urine of fertile male
      conspecifics, tree shrews of both sexes cover the scent marks with their own
      sternal-gland secretion by "chinning." The urine of other species, female
      conspecifics, or castrated male conspecifics does not elicit this behavior; that
      is, overmarking with sternal-gland secretion is a reaction to a specific chemical
      signal. The intensity of the overmarking reaction, i.e., the chinning score in
      response to the urine sample, decreases as the urine is diluted. The urine of
      different male conspecifics elicits overmarking of varying intensity; an animal's
      own urine is in general not overmarked. This behavioral reaction meets all the
      criteria for a bioassay of potential use in isolating the tree-shrew pheromone
      from urine. 

PMID- 24306401
TI  - Chemical and behavioral analyses of volatile sex pheromone components released by
      callingHeliothis virescens (F.) females (Lepidoptera: Noctuidae).
AB  - Gas chromatographic and mass spectral analyses were conducted on pheromone gland
      extracts, volatiles collected from excised pheromone glands, and volatiles
      collected from calling females. In addition to tetradecanal, (Z)-9-tetradecenal,
      hexadecanal, (Z)-7-hexadecenal, (Z)-9-hexadecenal, and (Z)-11-hexadecenal, four
      other compounds, tetradecanol, (Z)-9-tetradecenol, hexadecanol, and (Z)-11
      hexadecenol, were also identified from gland extracts. Only the six aldehyde
      components were found in gland and female volatile collections. The mean
      percentage of components identified from volatiles collected from calling females
      was 13.0% tetradecanal, 18.1% (Z)-9-tetradecenal, 7.3% hexadecanal, 0.6% (Z)-7
      hexadecenal, 1.0% (Z)-9-hexadecenal, and 60.0% (Z)-11-hexadecenal. Bioassays
      using rubber septa formulated to release the female volatile blend indicated that
      all six aldehyde components play major roles in close-range male reproductive
      behavior. Deletion of (Z)-9-hexadecenal from the six-component blend reduced the
      number of copulation attempts while (Z)-7-hexadecenal exerted subtle effects on
      all close range behaviors. Tetradecanal affected the number of times males
      reorient from close range. Deletion of hexadecanal from the six-component blend
      resulted in a significant reduction in the number of times males landed.
      Comparison of the six-component synthetic blend (released at somewhat less than 1
      female equivalent per hour) with calling females indicated that the six-component
      blend was indistinguishable from the females in inducing all of the behaviors
      monitored. 

PMID- 24306402
TI  - Synthesis of diastereomeric mixture of 15,19,23-trimethylheptatriacontane,
      contact sex pheromone of tsetse fly,Glossina morsitans morsitans westwood.
AB  - A nine-step synthesis is described for a diastereomeric mixture of 15,19,23
      trimethylheptatriacontane, a contact sex pheromone ofGlossina morsitans morsitans
      Westwood. The compound has been synthesized by means of double alkylation of
      diethyl 3-oxoglutarate (DEOG) with 3-methyl-2-heptadecenyl methanesulfonate,
      which was readily prepared from 1-hexadecene, as the key step. 

PMID- 24306403
TI  - Chemical identification and behavioral characterization of male wing pheromone
      ofEphestia elutella (Pyralidae).
AB  - Behavioral and chemical evidence is presented for the identity of the male wing
      pheromone ofEphestia elutella (Hubner) and the role of this pheromone in
      courtship success is evaluated. Males with the forewing removed experienced a
      mating success rate less than half of that of either intact males or males that
      had only the wing gland area remaining of their forewings. GC-MS analysis and
      microchemical reactions indicated the presence of (E)-phytol and a series of
      saturated gamma-lactones in a methylene chloride extract of the wings. Using an
      assay of female courtship behavioral response, (E)-phytol was found to evoke an
      intermediate level of response in females when presented alone, while the
      complete array of insect-derived gamma-lactones produced no significant response.
      The combination of either gamma-decalactone or gamma-undecalactone with (E)
      phytol in a 1?2 ratio, however, elicited a female response equivalent to that
      produced by the unfractionated wing extract. 

PMID- 24306404
TI  - Effect of combined feeding stimuli on ingestion by the nematodeTrichostrongylus
      colubriformis.
AB  - Ingestion by the nematodeTrichostrongylus colubriformis was stimulated by
      serotonin, histamine, and dopamine. Immune serum inhibited feeding by both sexes
      while octopamine depressed feeding by only male nematodes. However, the combined
      influence of these excitatory and inhibitory stimuli is unknown. Feeding in vitro
      by both sexes of the nematodeT. colubriformis was similar in millimolar ratios of
      histamine and dopamine or histamine and serotonin, but not dopamine and
      serotonin. Feeding by nematodes that was stimulated by histamine, dopamine, and
      serotonin was decreased by subsequent exposure to octopamine. Conversely,
      elevated concentrations of histamine, dopamine, and serotonin decreased the
      inhibitory action of octopamine on helminth ingestion in vitro. Doses of immune
      serum also decreased the stimulated feeding of nematodes that was induced by
      histamine, dopamine or serotonin. However, the addition of elevated
      concentrations of these biogenic amines to immune serum reversed the inhibitory
      effect. The feeding activity of nematodes may represent a summation of the
      inhibitory and excitatory stimuli that occur in the chemical environment of the
      helminth. 

PMID- 24306405
TI  - Chemical fractionation of shrimp extracts inducing bottom food search behavior in
      cod (Gadus morhua L.).
AB  - The bottom food search (BFS) feeding behavior in cod (Gadus morhua L.), has been
      used in a bioassay for chemical isolation of the feeding stimulant substances
      present in shrimp (Pandalus borealis). An aqueous methanol extract of ground
      shrimp was separated into acidic, neutral, and amphoteric/basic fractions by ion
      exchange chromatography and into single components by preparative high-pressure
      liquid chromatography (HPLC). Of the isolated single components, the amino acid
      glycine was most potent, followed by alanine. Two unidentified substances were
      also highly potent. There was a synergistic effect between glycine, alanine,
      proline, and arginine. These four amino acids were more potent than the total
      amino acid pool found in the shrimp extract, indicating that there may be amino
      acids in this pool having an antagonistic effect. 

PMID- 24306406
TI  - Fate of ingested iridoid glycosides in lepidopteran herbivores.
AB  - Thin-layer chromatography was used to follow the fates of iridoid glycosides
      ingested by four species of lepidopteran herbivores. These four species differed
      in their feeding strategy, ranging from generalist to monophagous specialist; and
      in their predator avoidance strategy, ranging from cryptic and palatable to
      aposematic and unpalatable. The fates of the iridoid glycosides ranged from
      sequestration by the unpalatable specialist,Euphydryas phaeton (Nymphalidae); to
      passage into the hemolymph and eventual elimination in the meconium by the
      specialistsJunonia coenia (Nymphalidae) andCeratomia catalpas (Sphingidae); to
      elimination of the intact compounds in the feces of the generalist
      feeder,Lymantria dispar (Lymantriidae). 

PMID- 24306407
TI  - Reinvestigation of anhydroserricornin, (2S,3S)-2,6-diethyl-3,5-dimethyl-3,4
      dihydro-2H-pyran, as a sex pheromone component for male cigarette beetle.
AB  - Reinvestigation of the pheromonal activity of anhydroserricornin, (2S,3S)-2,6
      diethyl-3,5-dimethyl-3,4-dihydro-2H-pyran, showed that the magnitude of its
      activity was less than 1/10(3) of that of serricornin, 7-hydroxy-4,6-dimethyl-3
      nonanone, the sex pheromone of the cigarette beetleLasioderma serricorne (F.).
      Neither a synergistic nor an inhibitory effect of anhydroserricornin addition on
      the action of serricornin was observed. 

PMID- 24306408
TI  - Volatile fatty acids in urine and vaginal secretions of cows during reproductive
      cycle.
AB  - Levels of volatile fatty acids (VFA) in vaginal secretions (VS) of cows were
      nearly independent of concentration changes of acids in the gastrointestinal
      tract, while levels in urine showed marked dependence. During three-week cycles,
      the VFA concentrations in VS increased shortly before heat and decreased to one
      third on days 19-22. Some cows showed an immediate increase after heat while in
      others the increase was slow and gradual. Moderately increased levels at midcycle
      were probably related to interovulatory follicle growth. Content of VFA in VS of
      pregnant cows was significantly above the level of the postestrus drop. Some
      pregnant cows in the first two thirds of gravidity had substantially higher
      levels of VFA than the other cows. Changes in VFA levels have a potential value
      for estrus detection and pregnancy diagnosis in cows. The gas chromatographic
      method used is too slow and tedious for practical application, but a reliable
      semiquantitative test for rapid proof of VFA or acetic acid in VS would be a very
      useful device for field use. It would have a substantial impact on the economy of
      cattle production by minimizing the loss of time due to delayed breeding. 

PMID- 24306409
TI  - Species, individual and kin specific blends in Dufour's gland secretions of
      halictine bees : Chemical evidence.
AB  - The compositions of Dufour's gland secretions of four sympatric halictine bee
      species were chemically studied by combined gas chromatography-mass spectrometry.
      The secretion is composed of C16-C24 macrocyclic lactones, isopentenyl esters,
      and hydrocarbons. Comparative analyses have revealed that the blends of compounds
      are species specific. Studies of individual glands belonging to bees of the
      speciesEvylaeus malachurum have demonstrated that each bee exhibits a specific
      blend in its Dufour's gland. Nestmate bees (considered as sister bees), however,
      are more similar to each other than nonrelated bees. The relative importance of
      species specificity, individual specificity, and similarities between kins are
      discussed. 

PMID- 24306410
TI  - Allelopathic suppression of weed and nitrification by selected cultivars
      ofSorghum bicolor (L.) moench.
AB  - Root exudates of 100 cultivars ofSorghum bicolor L. (Moench) were screened for
      their ability to inhibit seed germination and seedling growth ofAmaranthus
      retroflexus L. Exudates of some of the test cultivars were found to inhibit
      significantly seed germination and/or seedling growth ofA. retroflexus, and most
      of the inhibitory activity was found in neutral and acetone fractions of root
      exudates. Testing of aqueous extracts and decaying residues of four
      selectedSorghum cultivars (two toxic and two nontoxic through root exudation)
      revealed that all four cultivars significantly reducedA. retroflexus growth and
      nitrification processes with greater inhibition achieved by the toxic cultivars.
      This study suggests a potential biological control ofAmaranthus and nitrification
      by someS. bicolor cultivars. 

PMID- 24306411
TI  - Effects of three phenolic acids on chlorophyll content and ions uptake in cowpea
      seedlings.
AB  - This study was conducted to test the hypothesis that interfering with chlorophyll
      metabolism and ion uptake may be mechanisms through which some phenolic acids
      inhibit the growth of cowpea seedlings. Three concentrations (10(-4) M, 5 * 10(
      4) M, and 10(-3) M) of each of syringic, caffeic, and protocatechuic acids were
      used to test their effects using sand-culture medium. It was found that seedling
      growth, chlorophyll a, total chlorophyll, chlorophyll a/b ratio, and the uptake
      of N, P, K, Fe, and Mo were significantly reduced by most of the test
      concentrations of the phenolic acids. However, chlorophyll b content and the Mg
      uptake were not significantly affected by all the phenolic acid concentrations.
      Calcium uptake was significantly inhibited by 5 * 10(-4) M and 10(-3) M of
      caffeic acid and 5 * 10(-4) M of protocatechuic acid. In most cases, the
      reduction in dry weight was parallel to the reduction in chlorophyll content and
      ion uptake, and the reduction in chlorophyll was also parallel to the reduction
      in ion uptake. The relationships among the inhibition of dry weights, chlorophyll
      content, and ion uptake are briefly discussed. 

PMID- 24306412
TI  - Female sex pheromone of the melonworm,Diaphania hyalinata (Lepidoptera:
      Pyralidae), and analysis of male responses to pheromone in a flight tunnel.
AB  - Ten C16 chain-length compounds were identified from heptane extracts of
      ovipositors of female melonworm,Diaphania hyalinata (L.). The major constituents
      of the extracts were (E)-11-hexadecenal and (E,E)-10,12-hexadecadienal [(E,E)
      10,12-16:Ald] and the alcohols and acetates of these olefins were found in trace
      amounts (<2%). Extracts also contained traces of (E,Z)- and (Z,Z)-10,12-16:Ald,
      hexadecanal, and 1-hexadecanol. Analysis of the behavioral responses of males to
      synthetic mixtures of these compounds and responses to ovipositor extracts in a
      flight tunnel showed that a synthetic mixture of the 10 compounds elicited a
      behavioral repertoire from males that was indistinguishable from that elicited by
      ovipositor extract. Flight tunnel studies also indicated that six of the 10
      compounds probably represent the essential components of the female's sex
      pheromone. 

PMID- 24306413
TI  - Female sex pheromone of the pickleworm,Diaphania nitidalis (Lepidoptera:
      Pyralidae).
AB  - Heptane extracts of the ovipositors from pickleworm adults (Diaphania nitidalis)
      were found to contain (E)-11-hexadecenal along with proportionally smaller
      amounts of (Z)-11-hexadecenal, (E)- and (Z)-11-hexadecen-1-ol, hexadecanol,
      hexadecanal, and a trace amount of (E,Z)-10,12-hexadecadienal. Assays conducted
      in a flight tunnel and in the field showed that a synthetic mixture of the five
      unsaturated compounds elicited behavioral responses from pickleworm males that
      were indistinguishable from those elicited by extracts of the female or by mate
      calling females. When any component was deleted from the set of five unsaturated
      compounds, the intensity and extent of male responses to the resulting mixtures
      were significantly attenuated. The female sex pheromone of the pickleworm
      resembles the pheromone of a congeneric species,D. hyalinata, but bioassays
      indicated that (E,E)-10,12-hexadecadienal, produced byD. hyalinata but not by the
      pickleworm, plays a role in pheromonal specificity. 

PMID- 24306414
TI  - Synthesis of pungenin, a foliar constituent of some spruce species, and
      investigation of its efficacy as a feeding deterrent for spruce budworm
      [Choristoneura fumiferana (Clem.)].
AB  - Pungenin was synthesized from 3,4-dihydroxyacetophenone by a short sequence
      involving manipulation of protecting groups on the 3 and 4 hydroxyl functions.
      Bioassays indicated that the glucoside is a modest feeding deterrent for sixth
      instar spruce budworm larvae, but it does not appear to retard the development of
      small larvae or lead to increased mortality. 

PMID- 24306415
TI  - Chemical attractants tested against the Australian bush flyMusca vetustissima
      (Diptera: Muscidae).
AB  - A number of chemical compositions known to attract several synanthropic and pest
      fly species were tested against the Australian bush flyMusca vetustissima, a
      severe and persistent pest of man and domesticated and wild mammals. A standard
      composition containing small quantities of trimethylamine and indole, blended
      with large amounts of ammonium sulfate and anchovy meal, showed good attractancy
      against this fly. Deletion of ammonium sulfate did not significantly alter
      attractancy. Similarly, incorporation ofn-butyric acid and linoleic acid into the
      formulation did not alter attractancy, nor did addition of several carbonates and
      bicarbonates. Skatole, a closely related compound to indole, decreased
      attractancy significantly. In all the tests, the attractant compositions lured
      greater number of females than males. The attractancy of the standard composition
      was studied and compared with equal amount of fresh cattle dung. Chemical
      attractants lured bush flies and not dung beetles, while dung attracted both
      flies and beetles. The dung resource was 4.6 * more attractive to flies than the
      standard attractant composition. This suggests that there are other chemical
      attractants emanating from dung that warrant isolation and identification work.
      Nevertheless, the chemical attractants studied here provide a starting point for
      further investigations. The ratio of female to male flies attracted to humans was
      greater than the ratio of flies attracted to chemicals. The sex ratio of flies
      netted from human host was 3.0, while the sex ratio of flies attracted to
      chemical attractants was 1.8. The preponderance of females attracted to both
      sources was probably due to physiological requirements of the sexes. 

PMID- 24306416
TI  - Chemical detection of "self" and conspecifics by crayfish.
AB  - Stimulus waters were used to examine behaviorally chemical communication in
      female crayfishProcambarus clarkii. Animals detected conspecifics. Response to
      stimulus water drawn from the animal's own tank, "self " water, mimicked either
      response to distilled water or response to water drawn from the tank of another
      animal. The response to "self" water depended on the relative concentration of
      substance(s) in "self" water stimuli to that of the same substance(s) in the test
      animal's tank. 

PMID- 24306417
TI  - Urinary volatile constituents of the house mouse,Mus musculus, and their
      endocrine dependency.
AB  - Mouse urine contains a great number of volatile constituents that may be used in
      chemical communication. Some of these volatiles, identified in this study by
      combined gas chromatography-mass spectrometry and gas chromatography-Fourier
      transform infrared spectroscopy, appear unique to the mouse. Certain urinary
      volatiles exhibit strong dependence on the sex and endocrine status of the
      animals, as shown through castration, treatment with an antiandrogen, and hormone
      supplementation. 

PMID- 24306418
TI  - Chemical scent constituents in urine of wolf (Canis lupus) and their dependence
      on reproductive hormones.
AB  - The volatile components of castrated male and ovariectomized female wolf urine
      were investigated and correlated with the administration of testosterone or
      estradiol and progesterone. The results indicate that testosterone induces in the
      castrated male the formation of some compounds typically associated with the
      intact male, while reducing the levels of some compounds associated with
      castrated male and female. The production of some of the "male" compounds was
      also induced in the ovariectomized female, although at lower levels. Changes in
      hormone levels during treatment of females are reflected in the composition of
      the urinary volatiles. Consequently, many of these compounds could be used to
      communicate gender as well as reproductive status. 

PMID- 24306419
TI  - Comparative analysis of Papaver somniferum genotypes having contrasting latex and
      alkaloid profiles.
AB  - Papaver somniferum produces therapeutically useful benzylisoquinoline alkaloids
      (BIAs) like papaverine, thebaine, codeine, and morphine that accumulate in its
      capsular latex. Morphine is a potent analgesic but is also abused as a narcotic,
      which has increased the demand for non-narcotic thebaine that can be converted
      into various analgesics. To curtail the narcotic menace, many distinct genotypes
      of the plant have been developed that are deficient in morphine and/or latex.
      Sujata is one such latex-less low alkaloid-producing variety developed from the
      alkaloid-rich gum harvest variety Sampada. Its utility for gene prospecting and
      studying differential gene regulation responsible for its low alkaloid, nutritive
      seed oil, and latex-less phenotype has been exploited in this study. BIA
      profiling of Sujata and Sampada capsules at the early and late stages indicated
      that except for thebaine, Sujata had a depressed alkaloid phenotype as compared
      to Sampada. Comparative transcript-based analysis of the two genotypes was
      carried out in the early stage capsule (higher thebaine) using subtractive
      hybridization and microarray. Interrogation of a P. somniferum array yielded many
      differentially expressing transcripts. Their homology-based annotation classified
      them into categories--latex related, oil/lipid related, alkaloid related, cell
      wall related, and others. These leads will be useful to characterize the highly
      sought after Sujata phenotype.

PMID- 24306420
TI  - Bulk spin-crossover in the complex [FeL(NCS)2] of a tris(pyridyl)ethane-derived
      N4-ligand--a temperature-dependent crystallographic study.
AB  - We have recently shown that the vacuum-deposited complex [Fe(II)L(NCS)2] (L: 1-{6
      [1,1-di(pyridin-2-yl)ethyl]-pyridin-2-yl}-N,N-dimethylmethanamine) is capable of
      a thermally induced spin crossover (SCO) in direct contact with a graphite
      surface. The SCO significantly differs from the transition behaviour in the bulk
      phase (powder). In the present work, the assumption of virtually no
      intermolecular interaction in the powder is confirmed by comparison with the spin
      transition in acetone solution (T1/2 = 234[3] K, DeltaT80 = 58[4] K), as
      monitored by temperature-dependent UV/Vis spectroscopy. The complex crystallises
      from chlorocarbons in the form of a number of pseudopolymorphs. Amongst these,
      the sufficiently stable solvate [Fe(II)L(NCS)2].CHCl3 is investigated by variable
      temperature single-crystal X-ray diffractometry. Its SCO behaviour (T1/2 = 240[3]
      K, DeltaT80 = 35[4] K) correlates with features of molecular structure that are
      unambiguously identified by analysis of the tensor of thermal expansion.
      Following comprehensive comparison of spin-transition properties in different
      states of aggregation (also in relation to the newly synthesised high-spin
      iron(ii) and iron(iii) complexes [Fe(II)Cl2L] and [Fe(III)Cl2L]PF6), a mode of
      adsorption on graphite surfaces is proposed, that complies with all previous
      findings. 

PMID- 24306422
TI  - Iodine uptake and prostate cancer in the TRAMP mouse model.
AB  - Iodine supplementation exerts antitumor effects in several types of cancer.
      Iodide (I-) and iodine (I2) reduce cell proliferation and induce apoptosis in
      human prostate cancer cells (LNCaP and DU-145). Both chemical species decrease
      tumor growth in athymic mice xenografted with DU-145 cells. The aim of this study
      was to analyze the uptake and effects of iodine in a preclinical model of
      prostate cancer (transgenic adenocarcinoma of the mouse prostate [TRAMP]
      mice/SV40-TAG antigens), which develops cancer by 12 wks of age. 125I- and 125I2
      uptake was analyzed in prostates from wild-type and TRAMP mice of 12 and 24 wks
      in the presence of perchlorate (inhibitor of the Na+/I- symporter [NIS]). NIS
      expression was quantified by quantitative polymerase chain reaction (qPCR). Mice
      (6 wks old) were supplemented with 0.125 mg I- plus 0.062 mg I2/mouse/day for 12
      or 24 wks. The weight of the genitourinary tract (GUT), the number of acini with
      lesions, cell proliferation (levels of proliferating cell nuclear antigen [PCNA]
      by immunohistochemistry), p53 and p21 expression (by qPCR) and apoptosis
      (relative amount of nucleosomes by enzyme-linked immunosorbent assay) were
      evaluated. In both age-groups, normal and tumoral prostates take up both forms of
      iodine, but only I- uptake was blocked by perchlorate. Iodine supplementation
      prevented the overexpression of NIS in the TRAMP mice, but had no effect on the
      GUT weight, cell phenotype, proliferation or apoptosis. In TRAMP mice, iodine
      increased p53 expression but had no effect on p21 (a p53-dependent gene). Our
      data corroborate NIS involvement in I- uptake and support the notion that another
      transporter mediates I2 uptake. Iodine did not prevent cancer progression. This
      result could be explained by a strong inactivation of the p53 pathway by TAG
      antigens.

PMID- 24306421
TI  - Emerging role of high-mobility group box 1 (HMGB1) in liver diseases.
AB  - Damage-associated molecular pattern (DAMP) molecules are essential for the
      initiation of innate inflammatory responses to infection and injury. The
      prototypic DAMP molecule, high-mobility group box 1 (HMGB1), is an abundant
      architectural chromosomal protein that has location-specific biological
      functions: within the nucleus as a DNA chaperone, within the cytosol to sustain
      autophagy and outside the cell as a DAMP molecule. Recent research indicates that
      aberrant activation of HMGB1 signaling can promote the onset of inflammatory and
      autoimmune diseases, raising interest in the development of therapeutic
      strategies to control their function. The importance of HMGB1 activation in
      various forms of liver disease in relation to liver damage, steatosis,
      inflammation, fibrosis, tumorigenesis and regeneration is discussed in this
      review. 

PMID- 24306423
TI  - Antiangiogenic and antitumoral effects mediated by a vascular endothelial growth
      factor receptor 1 (VEGFR-1)-targeted DNAzyme.
AB  - Antiangiogenesis is a promising antitumor strategy that inhibits tumor vascular
      formation to suppress tumor growth. DNAzymes are synthetic single-strand
      deoxyribonucleic acid (DNA) molecules that can cleave ribonucleic acids (RNAs).
      Here, we conducted a comprehensive in vitro selection of active DNAzymes for
      their activity to cleave the vascular endothelial growth factor receptor (VEGFR
      1) mRNA and screened for their biological activity in a matrigel tube-formation
      assay. Among the selected DNAzymes, DT18 was defined as a lead molecule that was
      further investigated in several model systems. In a rat corneal vascularization
      model, DT18 demonstrated significant and specific antiangiogenic activity, as
      evidenced by the reduced area and vessel number in VEGF-induced corneal
      angiogenesis. In a mouse melanoma model, DT18 was shown to inhibit B16 tumor
      growth, whereas it did not affect B16 cell proliferation. We further assessed the
      DT18 effect in mice with established human nasopharyngeal carcinoma (NPC). A
      significant inhibition of tumor growth was observed, which accompanied
      downregulation of VEGFR-1 expression in NPC tumor tissues. To evaluate DT18
      effect on vasculature, we performed dynamic contrast enhanced magnetic resonance
      imaging (DCE-MRI) on the human NPC xenograft mice treated with DT18 and showed a
      reduction of the parameter of K(trans) (volume constant for transfer of contrast
      agent), which reflects the condition of tumor microvascular permeability. When
      examining the safety and tolerability of DT18, intravenous administration of Dz18
      to healthy mice caused no substantial toxicities, as shown by parameters such as
      body weight, liver/kidney function, and histological and biochemical analyses.
      Taken together, our data suggest that the anti-VEGFR-1 DNAzyme may be used as a
      therapeutic agent for the treatment of cancer, such as NPC. 

PMID- 24306424
TI  - Radiological work-up after mass casualty incidents: are ATLS guidelines
      applicable?
AB  - OBJECTIVES: In mass casualty incidents (MCI) a large number of patients need to
      be evaluated and treated fast. Well-designed radiological guidelines can save
      lives. The purpose of this study was to evaluate the Advanced Trauma Life Support
      (ATLS) radiological guidelines in the MCI of an aeroplane crash. METHODS: Medical
      data of all 126 survivors of an aeroplane crash were analysed. Data included type
      and body region of the radiological studies performed on the survivors,
      Abbreviated Injury Score (AIS) and Injury Severity Score (ISS) codes and trauma
      care level of the hospitals. RESULTS: Ninety patients (72 %) underwent one or
      more imaging studies: in total 297 radiographs, 148 CTs and 18 ultrasounds were
      performed. Only 18 % received diagnostic imaging of all four body regions as
      recommended by ATLS. Compliance with ATLS was highest (73.3 %) in severely
      injured victims (ISS >=16); this group underwent two thirds of the (near) total
      body CTs, all performed in level I trauma centres. CONCLUSION: Overall compliance
      with ATLS radiological guidelines was low, although high in severely injured
      patients. Level I trauma centres frequently used (near) total body CT. Deviation
      from ATLS guidelines in radiological work-up in less severely injured patients
      can be safe and did not result in delayed diagnosis of serious injury. KEY
      POINTS: * Radiological imaging protocols can assist the management of mass
      casualty incidents needs. * Advanced Trauma Life Support (ATLS) radiological
      guidelines have been developed. * But radiological guidelines have not frequently
      been applied in aeroplane crashes. * Aircraft accidents are of high energy so
      ATLS guidelines should be applied. * Following mass casualty incidents total body
      CT seems appropriate within ATLS protocols.

PMID- 24306425
TI  - Clinical application of bilateral high temporal and spatial resolution dynamic
      contrast-enhanced magnetic resonance imaging of the breast at 7 T.
AB  - OBJECTIVE: The objective of our study was to evaluate the clinical application of
      bilateral high spatial and temporal resolution dynamic contrast-enhanced magnetic
      resonance imaging (HR DCE-MRI) of the breast at 7 T. METHODS: Following
      institutional review board approval 23 patients with a breast lesion (BIRADS 0, 4
      5) were included in our prospective study. All patients underwent bilateral HR
      DCE-MRI of the breast at 7 T (spatial resolution of 0.7 mm(3) voxel size,
      temporal resolution of 14 s). Two experienced readers (r1, r2) and one less
      experienced reader (r3) independently assessed lesions according to BI-RADS(r).
      Image quality, lesion conspicuity and artefacts were graded from 1 to 5.
      Sensitivity, specificity and diagnostic accuracy were assessed using
      histopathology as the standard of reference. RESULTS: HR DCE-MRI at 7 T revealed
      29 lesions in 23 patients (sensitivity 100 % (19/19); specificity of 90 % (9/10))
      resulting in a diagnostic accuracy of 96.6 % (28/29) with an AUC of 0.95. Overall
      image quality was excellent in the majority of cases (27/29) and examinations
      were not hampered by artefacts. There was excellent inter-reader agreement for
      diagnosis and image quality parameters (kappa = 0.89-1). CONCLUSION: Bilateral HR
      DCE-MRI of the breast at 7 T is feasible with excellent image quality in clinical
      practice and allows accurate breast cancer diagnosis. KEY POINTS: * Dynamic
      contrast-enhanced 7-T MRI is being developed in several centres. * Bilateral high
      resolution DCE-MRI of the breast at 7 T is clinically applicable. * 7-T HR DCE
      MRI of the breast provides excellent image quality. * 7-T HR DCE-MRI should
      detect breast cancer with high diagnostic accuracy.

PMID- 24306426
TI  - Assessment of the nature of residual masses at end of treatment in lymphoma
      patients using volume perfusion computed tomography.
AB  - OBJECTIVES: To determine the diagnostic benefit of volume perfusion computed
      tomography (VPCT) at end of treatment for response assessment in lymphoma
      patients. METHODS: Seventy-five patients with different lymphoma subtypes were
      included: 50/75 patients had residual masses at end of treatment, 26/50 patients
      underwent VPCT at baseline and at end of treatment, and 24/50 patients only had
      end-of-treatment VPCTs. We evaluated the size of the main lymphoma mass, its
      blood flow (BF), blood volume (BV) and k-trans, calculated ratios (baseline and
      end of treatment) as well as sensitivity/specificity/negative (NPV)/positive
      predictive values (PPV). For VPCT at end of treatment, a cutoff threshold between
      responders and non-responders was calculated. RESULTS: For patients undergoing
      VPCT at baseline and end of treatment, reduction in size, BF, BV and k-trans was
      significant (P < 0.001). Identification of non-response was reached at: <53%
      reduction in size (sensitivity/specificity/accuracy/PPV/NPV of
      88.89%/62.5%/80.77%/84.21%/71.43%), <15% reduction of BF
      (sensitivity/specificity/accuracy/PPV/NPV of 100%/37.5%/80.77%/0.26%/100%), or
      <45% reduction of k-trans (sensitivity/specificity/accuracy/PPV/NPV of
      88.89%/75%/84.62%/88.89%/75%). In the subgroup undergoing VPCT at end of
      treatment, BF >18.51 ml/100 ml indicated non-responsiveness (sensitivity 92.86%,
      specificity 72.73%, accuracy 84%, PPV 81.25%, NPV 88.89%). CONCLUSIONS: VPCT
      seems adequate for assessment of lymphoma response at end of treatment. The
      degree of residual lymphoma perfusion at end of treatment helps to identify
      patients likely to remain in remission 1 year after completion of therapy. KEY
      POINTS: * Volume perfusion computed tomography (VPCT) offers measurements for
      assessing tumour response. * Perfusion parameter changes measured by VPCT
      correlate with antitumour therapy response. * In lymphoma, baseline and end-of
      treatment perfusion parameter ratios can predict response. * Perfusion
      measurements after treatment identify patients likely to remain in remission.

PMID- 24306427
TI  - Hepatic tuberculoma mimicking hepatocellular carcinoma in an immunocompetent
      host.
AB  - Hepatic tuberculosis as a part of disseminated tuberculosis is seen in 50-80% of
      cases. Isolated hepatic tuberculosis is very uncommon even in countries with high
      prevalence of tuberculosis. It can occur as a primary case or due to reactivation
      of an old tubercular focus. We report a case of a 59-year-old Caucasian woman who
      presented with persistent right upper quadrant pain and a hepatic lesion on an
      abdominal CT. She had a history of pulmonary tuberculosis 15 years ago with
      localised lung tuberculosis treated with lobectomy and antituberculous drugs. 

PMID- 24306428
TI  - Phalangeal lytic lesion: do not forget osseous sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease that most commonly involves the
      lung and thoracic lymph nodes. However, any organ can be affected. Osseous
      sarcoidosis has been reported in 3-13% of the cases. The skeletal involvement on
      radiographs is usually seen late in the course of the disease and is rarely the
      initial manifestation. We report a case of sarcoidosis revealed by a lytic lesion
      of the phalanx. 

PMID- 24306429
TI  - A reversible cause of 'end-stage renal disease': discrepant findings in serial
      duplex ultrasonograms in a suspected occlusion of a renal arterial bypass graft.
AB  - Duplex ultrasonography may be inaccurate due to a number of variables in operator
      and patient characteristics. We describe a 40-year-old woman who presented with
      acute kidney injury after prior complex abdominal aortic surgery that had left
      her with an essentially solitary functional kidney. On the basis of normal
      Doppler findings, she was started on dialysis. Owing to high clinical suspicion
      and a failure of renal function to return, a second Doppler study was performed 3
      weeks after the first, revealing the characteristic tardus-parvus waveform of
      renal artery stenosis. The patient underwent urgent renal arterial angioplasty
      and stent placement. She experienced an immediate increase in urinary output,
      required no further dialysis, and the creatinine improved to 1.7 mg/dL (her prior
      renal baseline). The case illustrates an important complication of abdominal
      aortic aneurysm repair, draws attention to a potential source of error in the
      Doppler measurement, and underscores the limitations of duplex ultrasonography
      for excluding renal artery stenosis in the presence of high pretest probability. 

PMID- 24306430
TI  - Normal chest X-ray should not mislead.
AB  - A lung ultrasound (US) can be routinely performed at the bedside by a trained
      intensive care unit physician and may provide accurate information about a lung's
      status that has diagnostic and therapeutic relevance. Oesophageal perforations
      are rare, and due to the rarity of this type of perforation and its non-specific
      presentation, the diagnosis and treatment are delayed, leading to a high
      mortality rate. We present a 70-year-old woman with a postoesophagoscopy
      perforated oesophagus. Lung US detected pneumothorax and mild pleural effusion
      that were not present on the postoperative chest X-ray. The early detection of
      the perforation led to a good outcome. 

PMID- 24306431
TI  - Large hepatic adenoma in a 21-year-old male.
AB  - Hepatic adenoma is an uncommon benign lesion of the liver that occurs more
      frequently in women in their third and fourth decades. The female/male ratio is
      up to 11:1. Hepatic adenomas may be single or multiple occasionally reaching
      sizes up to 20 cm. They are non-cancerous lesions, however they can become
      malignant. We present a 21-year-old male patient with no medical history who
      presented with abdominal pain, a palpable abdominal mass, abnormal liver function
      tests and a 14 kg weight loss in a 2-year period. A CT scan was performed with a
      17 cm tumour compressing intrahepatic bile ducts. The patient underwent a right
      hepatectomy with no complications. Histopathological analysis of the tumour
      revealed a hepatic adenoma with central necrosis. The patient is asymptomatic at
      1-year follow-up. 

PMID- 24306432
TI  - Bilateral sleeve fractures of the patella in a 12-year-old boy with hereditary
      spastic paraparesis and crouch gait.
AB  - This is the first reported case of bilateral sleeve fractures of the patellae in
      a child with crouch gait. A 12-year-old boy with hereditary spastic paraparesis
      (HSP), who was found to have mid-stance crouch of 20 degrees  on previous gait
      analysis, presented with pain of gradual onset and limited mobility. There was no
      history of trauma. Three-dimensional gait analysis showed that extensor mechanism
      function during loading response was intact, but knee flexion in swing was
      significantly reduced, indicating protective guarding by rectus femoris. X-rays
      showed bilateral minimally displaced sleeve fractures of the patellae. These were
      treated with immobilisation in cylinder casts in extension for 4 weeks. Follow-up
      X-rays showed that the fractures had successfully united and the patient
      progressed to full weight bearing and mobility as tolerated. 

PMID- 24306433
TI  - Optical coherence tomography assessment of vessel wall degradation in thoracic
      aortic aneurysms.
AB  - Optical coherence tomography images of human thoracic aorta from aneurysms reveal
      elastin disorders and smooth muscle cell alterations when visualizing the media
      layer of the aortic wall. These disorders can be employed as indicators for wall
      degradation and, therefore, become a hallmark for diagnosis of risk of aneurysm
      under intraoperative conditions. Two approaches are followed to evaluate this
      risk: the analysis of the reflectivity decay along the penetration depth and the
      textural analysis of a two-dimensional spatial distribution of the aortic wall
      backscattering. Both techniques require preprocessing stages for the
      identification of the air-sample interface and for the segmentation of the media
      layer. Results show that the alterations in the media layer of the aortic wall
      are better highlighted when the textural approach is considered and also agree
      with a semiquantitative histopathological grading that assesses the degree of
      wall degradation. The correlation of the co-occurrence matrix attains a
      sensitivity of 0.906 and specificity of 0.864 when aneurysm automatic diagnosis
      is evaluated with a receiver operating characteristic curve.

PMID- 24306434
TI  - Limb swelling in a pediatric sickle cell patient after revaccination with
      pneumococcal vaccine.
AB  - CASE (DESCRIPTION): This report describes an incident of limb swelling after
      revaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). A
      5-year old female with sickle cell disease experienced severe arm swelling with
      edema to the extent that it was difficult to put a shirt over the arm. The day
      prior, she received PPSV23 concomitantly with the meningococcal vaccine. She had
      received the PPSV23 vaccine 2.5 years prior to the event. The patient was managed
      with analgesics, antiemetics, and antibiotic prophylaxis and the arm swelling
      resolved 24 h later. A decreased length of time between revaccination and
      concurrent administration with the meningococcal vaccine could have contributed.
      CONCLUSION: Although rare, limb swelling after revaccination could be a concern
      in special at-risk populations where repeated vaccination is necessary for
      pneumococcal protection.

PMID- 24306435
TI  - A conceptual framework of patient satisfaction with a pharmacy adherence service.
AB  - BACKGROUND: Patients do not adhere to their medicines for a host of reasons which
      can include their underlying beliefs as well as the quality of their interactions
      with healthcare professionals. One way of measuring the outcome of pharmacy
      adherence services is to assess patient satisfaction but no questionnaire exists
      that truly captures patients' experiences with these relatively new services.
      OBJECTIVE: Our objective was to develop a conceptual framework specific to
      patient satisfaction with a community pharmacy adherence service based on
      criteria used by patients themselves. SETTING: The study was based in community
      pharmacies in one large geographical area of the UK (Surrey). All the work was
      conducted between October 2008 and September 2010. METHODS: This study involved
      qualitative non-participant observation and semi-structured interviewing. We
      observed the recruitment of patients to the medicines use review (MUR) service
      and also actual MUR consultations (7). We also interviewed patients (15). Data
      collection continued until no new themes were identified during analysis. We
      analysed interviews to firstly create a comprehensive account of themes which had
      significance within the transcripts, then created sub-themes within super
      ordinate categories. We used a structure-process-outcome approach to develop a
      conceptual framework relating to patient satisfaction with the MUR. Favourable
      ethical opinion for this study was received from the NHS Surrey Research Ethics
      Committee on 2nd June 2008. RESULTS: Five super-ordinate themes linked to patient
      satisfaction with the MUR service were identified, including relationships with
      healthcare providers; attitudes towards healthcare providers; patients'
      experience of health, healthcare and medicines; patients' views of the MUR
      service; the logistics of the MUR service. In the conceptual framework, structure
      was conceptualised as existing relationships, environment, and time; process was
      conceptualised as related to recruitment and consultation stages; and outcome as
      two concepts of immediate patient outcomes and satisfaction on reflection.
      CONCLUSION: We identified and highlighted factors that can influence patient
      satisfaction with the MUR service and this led to the development of a conceptual
      framework of patient satisfaction with the MUR service. This can form the basis
      for developing a questionnaire for measuring patient satisfaction with this and
      similar pharmacy adherence services.

PMID- 24306436
TI  - A comprehensive review of the impact of clinical pharmacy services on patient
      outcomes in mental health.
AB  - BACKGROUND: The importance of pharmacists in mental healthcare is starting to be
      recognised around the world. However few studies have focused on the evidence
      supporting pharmacist involvement in the inpatient mental healthcare setting.
      AIM: Evaluate types of outcomes achieved and level of evidence supporting
      clinical pharmacy services in inpatient mental health settings. METHODS: Medline,
      PyscINFO and International Pharmaceutical Abstracts databases were searched from
      January 1990 to March 31 2013. Studies were included if in an inpatient setting,
      published in English, and reported an intervention provided by a pharmacist or
      involving a pharmacist with a pivotal role in an intervention team. Data were
      extracted according to sample population and size, study design and outline,
      country, role of the pharmacist in the study, and the main results of the study.
      The level of evidence for each study was assessed using Australia's National
      Health and Medical Research Council's hierarchy of clinical evidence and results
      were categorised as having economic, clinical and/or humanistic outcomes.
      RESULTS: Eighteen articles met the inclusion criteria. A range of pharmaceutical
      services provided by pharmacists in inpatient mental healthcare were identified.
      These services highlight the role of pharmacists as reviewers of medication
      charts, laboratory results and medication prescribing and as educators of
      patients and other health care professionals. Six studies included a control or
      comparison group and had pre and post intervention measures. These comprised of
      three randomised control trials, one historical control study and two case series
      post and pre-post tests, corresponding to evidence levels of II, III-3 and IV
      respectively. Seven studies reported clinical outcomes, two economical and one
      humanistic outcomes. One study reported both clinical and economical outcomes.
      Seven studies focused on impact evaluation measures. CONCLUSIONS: Pharmacists
      provide a variety of services and play a significant role in inpatient mental
      healthcare. However, the level of evidence supporting these services is limited
      and the type of outcomes achieved is narrow.

PMID- 24306437
TI  - Can perception of aperture passability be improved immediately after practice in
      actual passage? Dissociation between walking and wheelchair use.
AB  - Perception of the fit between a person's action capabilities and relevant
      environmental properties (i.e., affordances) is often fine tuned gradually
      through experience performing a behavior. However, the immediate effect of such
      practice on the improvement of affordance perception is unclear. The present
      study was designed to examine whether a critical factor in the immediate effect
      of such practice is the opportunity to detect very fine differences between
      possible and impossible behaviors [i.e., high-resolution (HR) practice].
      Participants reported whether apertures of various widths were passable when
      walking while holding a 69-cm horizontal bar (Experiment 1) or when using a
      wheelchair (Experiment 2). When practicing passing through apertures, seven
      different aperture widths, including their minimum passable width (70 cm for both
      experiments) were presented around the affordance boundary with 1- or 5-cm
      increments for the HR or low-resolution (LR) conditions, respectively. Accuracy
      of perception of passability improved following both HR and LR practice when
      walking. In contrast, no improvement was observed in any condition when using a
      wheelchair. These findings suggest that the immediate effect of practice was
      mediated by the form of locomotion but not the resolution of the practice.

PMID- 24306438
TI  - Manipulating visual-motor experience to probe for observation-induced after
      effects in adaptation learning.
AB  - Observers can learn to move in novel, adapted environments after watching a
      learning or expert model. Although this is an effective practice technique, it is
      unclear how this learning is achieved and if observers update an internal model
      of their visual-motor environment, as shown through the presence of after-effects
      (i.e., negative carry-over effects when aiming in a normal environment following
      exposure to perturbed conditions). For such updating to occur via observational
      practice, it has been reasoned that the observer requires the motor capabilities
      to perform the task they are observing. To test this, we first trained three
      groups to physically move in clockwise (CW) or counterclockwise (CCW) rotated
      environments. When immediately returned to a normal environment, after-effects
      were seen. We then attempted to wash out these effects before allowing two of
      these groups (CW and CCW), and a naive observation only group, to watch a video
      of an actor performing in a CW environment. This observation phase was
      immediately followed by another test for after-effects and a direct test of
      learning when aiming in the rotated environment. Consistent with previous data,
      there were direct learning effects due to observation. Although after-effects
      increased for the experienced observers, these were small and were not
      significantly different from a physical practice only group that did not undergo
      the observation phase. Therefore, even with a motor repertoire for the rotated
      environment, there was a lack of evidence that observational practice results in
      implicit (re)updating of an internal model for aiming. 

PMID- 24306439
TI  - Contralateral tactile masking between forearms.
AB  - Masking effects have been demonstrated in which tactile sensitivity is affected
      when one touch is close to another on the body surface. Such effects are likely a
      result of local lateral inhibitory circuits that sharpen the spatial tuning of a
      given tactile receptor. Mutually inhibitory pathways have also been demonstrated
      between cortical tactile maps of the two halves of the body. Occasional reports
      have indicated that touches on one hand or forearm can affect tactile sensitivity
      at contralateral locations. Here, we measure the spatial tuning and effect of
      posture on this contralateral masking effect. Tactile sensitivity was measured on
      one forearm, while vibrotactile masking stimulation was applied to the opposite
      arm. Results were compared to sensitivity while vibrotactile stimulation was
      applied to a control site on the right shoulder. Sensitivity on the forearm was
      reduced by over 3 dB when the arms were touching and by 0.52 dB when they were
      held parallel. The masking effect depended on the position of the masking
      stimulus. Its effectiveness fell off by 1 STD when the stimulus was 29 % of arm
      length from the corresponding contralateral point. This long-range inhibitory
      effect in the tactile system suggests a surprisingly intimate relationship
      between the two sides of the body.

PMID- 24306440
TI  - Combined effects of auditory and visual cues on the perception of vection.
AB  - Vection is the illusion of self-motion in the absence of real physical movement.
      The aim of the present study was to analyze how multisensory inputs (visual and
      auditory) contribute to the perception of vection. Participants were seated in a
      stationary position in front of a large, curved projection display and were
      exposed to a virtual scene that constantly rotated around the yaw-axis,
      simulating a 360 degrees  rotation. The virtual scene contained either only
      visual, only auditory, or a combination of visual and auditory cues.
      Additionally, simulated rotation speed (90 degrees /s vs. 60 degrees /s) and the
      number of sound sources (1 vs. 3) were varied for all three stimulus conditions.
      All participants were exposed to every condition in a randomized order. Data
      specific to vection latency, vection strength, the severity of motion sickness
      (MS), and postural steadiness were collected. Results revealed reduced vection
      onset latencies and increased vection strength when auditory cues were added to
      the visual stimuli, whereas MS and postural steadiness were not affected by the
      presence of auditory cues. Half of the participants reported experiencing
      auditorily induced vection, although the sensation was rather weak and less
      robust than visually induced vection. Results demonstrate that the combination of
      visual and auditory cues can enhance the sensation of vection.

PMID- 24306442
TI  - Nutrient mitigation in a temporary river basin.
AB  - We estimate the nutrient budget in a temporary Mediterranean river basin. We use
      field monitoring and modelling tools to estimate nutrient sources and transfer in
      both high and low flow conditions. Inverse modelling by the help of PHREEQC model
      validated the hypothesis of a losing stream during the dry period. Soil and Water
      Assessment Tool model captured the water quality of the basin. The 'total daily
      maximum load' approach is used to estimate the nutrient flux status by flow
      class, indicating that almost 60% of the river network fails to meet nitrogen
      criteria and 50% phosphate criteria. We recommend that existing well-documented
      remediation measures such as reforestation of the riparian area or composting of
      food process biosolids should be implemented to achieve load reduction in close
      conjunction with social needs.

PMID- 24306443
TI  - Polycyclic aromatic hydrocarbon levels in European catfish from the upper Po
      River basin.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a major concern in environmental
      studies as many of them have been labeled as probable carcinogens by the
      International Agency for Research on Cancer (IARC 1983). Due to their lipophilic
      properties and resistance to degradation, PAHs can accumulate in organic tissue.
      As a consequence, alarming concentrations of these compounds have been found in
      many aquatic species. The European catfish (Silurus glanis) is a top food chain
      predator that is considered to be a reliable bio-indicator of environmental
      pollution. From 2009 to 2011, 54 specimens of S. glanis were captured from four
      different sites covering the area of the Po River basin (Northern Italy). Fish
      muscles were analyzed in the laboratory to determine the levels of nine PAHs,
      namely naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, pyrene,
      benz[a]anthracene, chrysene, and benz[a]pyrene (BaP), which were detected by high
      performance liquid chromatography (HPLC). The total average concentration of PAHs
      was 26.90 +/- 49.50 ng g(-1) (min 0.60, max 275.75 ng g(-1)). Analysis showed
      that 9.20% of the fish muscles exceeded the maximum levels of 2 ng g(-1) set for
      BaP by European regulations (Commission Regulation (EC), 2006). Values measured
      for benz[a]pyrene ranged from 0.05 to 8.20 ng g(-1) (mean 1.07 +/- 1.58 ng g(
      1)). Chrysene and benz[a]anthracene, both considered potential human carcinogens
      (PAH2), were found at levels of 4.40 and 0.05 ng g(-1) (mean values),
      respectively. The highest mean concentration was recorded for anthracene (12.92
      ng g(-1)), which has been recently included in the list of substances of very
      high concern (SVHC) as reported by the European Chemicals Agency (ECHA 1-9,
      2009).

PMID- 24306444
TI  - Transforming Pinus pinaster forest to recreation site: preliminary effects on
      LAI, some forest floor, and soil properties.
AB  - This study investigates the effects of forest transformation into recreation
      site. A fragment of a Pinus pinaster plantation forest was transferred to a
      recreation site in the city of Bartin located close to the Black Sea coast of
      northwestern Turkey. During the transformation, some of the trees were
      selectively removed from the forest to generate more open spaces for the
      recreationists. As a result, Leaf Area Index (LAI) decreased by 0.20 (about 11%).
      Additionally, roads and pathways were introduced into the site together with some
      recreational equipment sealing parts of the soil surface. Consequently, forest
      environment was altered with a semi-natural landscape within the recreation site.
      The purpose of this study is to assess the effects of forest transformation into
      recreation site particularly in terms of the LAI parameter, forest floor, and
      soil properties. Preliminary monitoring results indicate that forest floor
      biomass is reduced by 26% in the recreation site compared to the control site.
      Soil temperature is increased by 15% in the recreation site where selective
      removal of trees expanded the gaps allowing more light transmission. On the other
      hand, the soil bulk density which is an indicator of soil compaction is
      unexpectedly slightly lower in the recreation site. Organic carbon (C(org)) and
      total nitrogen (N(total)) together with the other physical and chemical parameter
      values indicate that forest floor and soil have not been exposed to much
      disturbance. However, subsequent removal of trees that would threaten the
      vegetation, forest floor, and soil should not be allowed. The activities of the
      recreationists are to be concentrated on the paved spaces rather than soil
      surfaces. Furthermore, long-term monitoring and management is necessary for both
      the observation and conservation of the site.

PMID- 24306445
TI  - Synthesis and in vitro evaluation of tetrahydroisoquinolines with pendent
      aromatics as sigma-2 (sigma2) selective ligands.
AB  - 5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3
      dimethoxybenzamide 1 is a potent and selective sigma2 receptor ligand suitable
      for further development. A series of new analogues, incorporating a variety of
      isoquinoline and carboxylic acid moieties, linked together with either a linear
      or cyclic amine spacer have been synthesised and assessed for their sigma1/sigma2
      binding affinity and selectivity. Compounds with a rigid piperidine spacer gave
      Ki values for the sigma2 receptor between 8.7-845 nM. Changing the configuration
      of the methoxy groups on the isoquinoline moiety resulted in molecules with
      sigma2Ki values of 4.4-133 nM whereas varying the length and flexibility of the
      carbon spaces gave sigma2Ki values 0.88-15.0 nM, some of the most active,
      selective sigma2 ligands to date. Thus, the flexibility and length of the carbon
      linker and the carboxylic acid moiety are confirmed to be key to the exceptional
      binding affinity and selectivity for this active series. Additionally, the
      incorporation of a halogen on selected carboxylic acid moieties provided a
      convenient strategy for the introduction of a radiohalogen for applications in
      pharmacological and imaging studies. 

PMID- 24306446
TI  - Sex-role conflicts and personal adjustment: A study of British adolescents.
AB  - A study employing British adolescents as subjects was conducted to test two
      hypotheses: (1) In learning to adjust to sex-role prescriptions in adolescence,
      females are more likely than males to experience conflict over sex-role issues
      and problems in personal adjustment, with high academically achieving females
      hypothesized to be most likely to evidence such conflicts. (2) Individuals of
      both sexes who experience high levels of sex-role conflict are most likely to
      evidence less adequate personal adjustment. Results were partially supportive of
      hypothesis 1. Though no sex differences were obtained for measures of personal
      adjustment, females appeared to experience more conflict over sex-role issues.
      Males also evidenced conflict, however, and there was not a uniform female
      disadvantage. No relationship for either sex was found between high academic
      ambition and less adequate adjustment. Support for hypothesis 2 was more
      consistent. Individuals of both sexes who experienced the highest levels of sex
      role conflict also experienced more problems in personal adjustment, but only
      when the conflict reflected a perception of the self as deficient in
      instrumental, "masculine," attributes in comparison with perceived societal
      expectations. Results and implications for future research are discussed. 

PMID- 24306447
TI  - Sex-role identification of normal adolescent males and females as related to
      school achievement.
AB  - The historical view of masculinity/femininity posited essentially bipolar
      opposites, with the presence of one set of characteristics precluding the other.
      More recent studies of sex-role stereotypes have defined sexual orientation
      within clusters of socially desirable attributes which males and females perceive
      as differentiating males from females. This view negates the contention that
      psychological sex roles are composed of bipolar opposites, and concludes that the
      constructs of masculinity and femininity are independent dimensions rather than a
      single bipolar dimension. Little is known about the sex-role functioning of
      adolescents, yet it is during adolescence that qualitative shifts occur in
      interpersonal relationships and concurrent changes occur in cognitive
      functioning, with adolescents shifting toward hypothetical thinking and abstract
      ideal notions. In view of these changes, much can be learned about adult
      functioning by studying the sex-role perceptions of adolescents related to
      familial and social variables. This study examines the sex-role perceptions that
      adolescents hold of fathers, mothers, ideal males, ideal females, and selves.
      Differences exist between male and female adolescents, and significant linkages
      exist between sex-role identification and academic achievement. 

PMID- 24306448
TI  - Delinquency: The role of self-esteem and social values.
AB  - Self-esteem and value orientation are recognized in several theories as important
      factors in the development of delinquency. In a comparison of these theories,
      value orientation and different aspects of self-esteem were assessed using an
      individually administered test battery with male delinquents, marginal
      delinquents, and nondelinquents. No value orientation or overall self-esteem
      differences were found. The results are interpreted as generally supportive of
      the Kaplan theory, which holds that delinquents use psychological defenses to
      enhance their self-esteem and to retain endorsement of socially accepted values. 

PMID- 24306449
TI  - Birth order and self-concept in adolescence.
AB  - The effect of birth order on self-concept was examined in a sample of adolescent
      boys and girls. Based upon self-theory, which suggests that the two main
      processes of self-concept formation (e.g., reflected appraisals and social
      comparisons) are affected by the power and role relationships associated with
      ordinal position in the family, several hypotheses were tested: (1) The self
      evaluations of only and oldest children are more positive than those of younger
      siblings; (2) middle-borns have the lowest self-evaluations; (3) these
      relationships are affected by the sex and spacing of nearest sibling; and (4) the
      self-conceptions of oldest and only children are more similar to those of their
      parents than the self-conceptions of younger siblings and their parents. Using
      analysis of variance and several different measures of self-evaluation, very
      little support was found for any of these hypotheses. The strongest support was
      found for the hypothesis on middle-borns, but even these relationships were not
      large. Several explanations are offered for these weak and inconsistent findings.

PMID- 24306450
TI  - Sizing up single-molecule enzymatic conformational dynamics.
AB  - Enzymatic reactions and related protein conformational dynamics are complex and
      inhomogeneous, playing crucial roles in biological functions. The relationship
      between protein conformational dynamics and enzymatic reactions has been a
      fundamental focus in modern enzymology. It is extremely difficult to characterize
      and analyze such complex dynamics in an ensemble-averaged measurement, especially
      when the enzymes are associated with multiple-step, multiple-conformation complex
      chemical interactions and transformations. Beyond the conventional ensemble
      averaged studies, real-time single-molecule approaches have been demonstrated to
      be powerful in dissecting the complex enzymatic reaction dynamics and related
      conformational dynamics. Single-molecule enzymology has come a long way since the
      early demonstrations of the single-molecule spectroscopy studies of enzymatic
      dynamics about two decades ago. The rapid development of this fundamental protein
      dynamics field is hand-in-hand with the new development of single-molecule
      imaging and spectroscopic technology and methodology, theoretical model analyses,
      and correlations with biological preparation and characterization of the enzyme
      protein systems. The complex enzymatic reactions can now be studied one molecule
      at a time under physiological conditions. Most exciting developments include
      active manipulation of enzymatic conformational changes and energy landscape to
      regulate and manipulate the enzymatic reactivity and associated conformational
      dynamics, and the new advancements have established a new stage for studying
      complex protein dynamics beyond by simply observing but by actively manipulating
      and observing the enzymatic dynamics at the single-molecule sensitivity
      temporally and spatially. 

PMID- 24306451
TI  - Controlling proton movement: electrocatalytic oxidation of hydrogen by a
      nickel(II) complex containing proton relays in the second and outer coordination
      spheres.
AB  - A nickel bis(diphosphine) complex containing proton relays in the second and
      outer coordination spheres, Ni(P(Cy)2N((CH2)2OMe))2, (P(Cy)2N((CH2)2OMe) = 1,5
      di(methoxyethyl)-3,7-dicyclohexyl-1,5-diaza-3,7-diphosphacyclooctane), is an
      electrocatalyst for hydrogen oxidation. The addition of hydrogen to the Ni(II)
      complex results in rapid formation of three isomers of the doubly protonated
      Ni(0) complex, [Ni(P(Cy)2N((CH2)2OMe)2H)2](2+). The three isomers show fast
      interconversion at 40  degrees C, unique to this complex in this class of
      catalysts. Under conditions of 1.0 atm H2 using H2O as a base, catalytic
      oxidation proceeds at a turnover frequency of 5 s(-1) and an overpotential of 720
      mV, as determined from the potential at half of the catalytic current. Compared
      to the previously reported Ni(P(Cy)2N(Bn))2 complex, the new complex operates at
      a faster rate and at a lower overpotential.

PMID- 24306452
TI  - Investigating children's spiritual experiences through the Health and Physical
      Education (HPE) learning area in Australian schools.
AB  - The purpose of this study is to explore spirituality within the Health and
      Physical Education (HPE) learning area, through investigating children's
      experiences within three Brisbane Catholic Education primary schools (Queensland,
      Australia). There are seven dimensions of wellness: physical, intellectual,
      emotional, social, spiritual, environmental, and occupational, which are all
      strongly connected (Robbins et al. in A wellness way of life, 9th edition, McGraw
      Hill, USA, 2011). It is logical that HPE, which promotes students to adopt
      lifelong health and well-being, offers opportunities for spirituality to be
      experienced and warrants investigation. Data gathered in this qualitative
      research suggest that regular quality inclusive HPE lessons increased students'
      potential for spiritual experiences. 

PMID- 24306454
TI  - eIF5A has a function in the cotranslational translocation of proteins into the
      ER.
AB  - The putative eukaryotic translation initiation factor 5A (eIF5A) is a highly
      conserved and essential protein present in all organisms except bacteria. To be
      activated, eIF5A requires the conversion of a specific residue of lysine into
      hypusine. This hypusine modification occurs posttranslationally in two enzymatic
      steps, and the polyamine spermidine is the substrate. Despite having an essential
      function in translation elongation, the critical role played by eIF5A remains
      unclear. In addition to demonstrating genetic interactions with translation
      factors, eIF5A mutants genetically interact with mutations in YPT1, which encodes
      an essential protein involved in endoplasmic reticulum (ER)-to-Golgi vesicle
      transport. In this study, we investigated the correlation between the function of
      eIF5A in translation and secretion in yeast. The results of in vivo translocation
      assays and genetic interaction analyses suggest a specific role for eIF5A in the
      cotranslational translocation of proteins into the ER, but not in the
      posttranslational pathway. Additionally, we observed that a block in eIF5A
      activation up-regulates stress-induced chaperones, which also occurs when SRP
      function is lost. Finally, loss of eIF5A function affects binding of the ribosome
      nascent chain complex to SRP. These results link eIF5A function in translation
      with a role of SRP in the cell and may help explain the dual effects of eIF5A in
      differential and general translation. 

PMID- 24306455
TI  - Separate mechanisms for age-related truncation and racemisation of peptide-bound
      serine.
AB  - Some amino acids are particularly susceptible to degradation in long-lived
      proteins. Foremost among these are asparagine, aspartic acid and serine. In the
      case of serine residues, cleavage of the peptide bond on the N-terminal side, as
      well as racemisation, has been observed. To investigate the role of the hydroxyl
      group, and whether cleavage and racemisation are linked by a common mechanism,
      serine peptides with a free hydroxyl group were compared to analogous peptides
      where the serine hydroxyl group was methylated. Peptide bond cleavage adjacent to
      serine was increased when the hydroxyl group was present, and this was
      particularly noticeable when it was present as the hydroxide ion. Adjacent amino
      acid residues also had a pronounced affect on cleavage at basic pH, with the
      SerPro motif being especially susceptible to scission. Methylation of the serine
      hydroxyl group abolished truncation, as did insertion of a bulky amino acid on
      the N-terminal side of serine. By contrast, racemisation of serine occurred to a
      similar extent in both O-methylated and unmodified peptides. On the basis of
      these data, it appears that racemisation of Ser, and cleavage adjacent to serine,
      occur via separate mechanisms. Addition of water across the double bond of
      dehydroalanine was not detected, suggesting that this mechanism was unlikely to
      be responsible for conversion of L-serine to D-serine. Abstraction of the alpha
      proton may account for the majority of racemisation of serine in proteins.

PMID- 24306453
TI  - Cloning, characterization and application of a glyceraldehyde-3-phosphate
      dehydrogenase promoter from Aspergillus terreus.
AB  - It is important to develop native and highly efficient promoters for effective
      genetic engineering of filamentous fungi. Although Aspergillus terreus is an
      important industrial fungus for the production of itaconic acid and lovastatin,
      the available genetic toolbox for this microorganism is still rather limited. We
      have cloned the 5' upstream region of the glyceraldehyde-3-phosphate
      dehydrogenase gene (gpd; 2,150 bp from the start codon) from A. terreus CICC
      40205 and subsequently confirmed its promoter function using sgfp (synthetic
      green fluorescent protein) as the reporter. The sequence of the promoter PgpdAt
      was further analysed by systematic deletion to obtain an effective and compact
      functional promoter. Two truncated versions of PgpdAt (1,081 and 630 bp) were
      also able to drive sgfp expression in A. terreus. The activities of these three
      PgpdAt promoters of varying different lengths were further confirmed by
      fluorescence, western blot and transcription. The shortest one (630 bp) was
      successfully applied as a driver of vgb expression in the genetic engineering of
      A. terreus. The function of expressed haemoglobin was demonstrated by the CO
      (carbon monoxide)-difference spectrum and enhanced oxygen uptake rate, glucose
      consumption and itaconic acid titer. Our study was successful in developing and
      validating an efficient and compact native promoter for genetic engineering of A.
      terreus. 

PMID- 24306456
TI  - A mild removal of Fmoc group using sodium azide.
AB  - A mild method for effectively removing the fluorenylmethoxycarbonyl (Fmoc) group
      using sodium azide was developed. Without base, sodium azide completely
      deprotected N (alpha)-Fmoc-amino acids in hours. The solvent-dependent conditions
      were carefully studied and then optimized by screening different sodium azide
      amounts and reaction temperatures. A variety of Fmoc-protected amino acids
      containing residues masked with different protecting groups were efficiently and
      selectively deprotected by the optimized reaction. Finally, a biologically
      significant hexapeptide, angiotensin IV, was successfully synthesized by solid
      phase peptide synthesis using the developed sodium azide method for all Fmoc
      removals. The base-free condition provides a complement method for Fmoc
      deprotection in peptide chemistry and modern organic synthesis. 

PMID- 24306457
TI  - Association of muscle-strengthening activity with knee and low back pain, falls,
      and health-related quality of life among Japanese older adults: a cross-sectional
      survey.
AB  - This study aimed to examine the association of muscle-strengthening activity with
      knee and low back pain, falls, and health-related quality of life among Japanese
      older adults. A cross-sectional survey targeted 3,000 people. The response rate
      was 52% and 208 respondents did not meet the inclusion criteria. Therefore, 1,351
      individuals were analyzed. Muscle-strengthening activity (exercise using
      equipment and body weight, lifestyle activities), knee and low back pain, falls
      over the past year, health-related quality of life (SF-8), and potential
      confounders were assessed. Individuals engaging in exercise using body weight and
      lifestyle activity (>= 2 days/week) were more likely to have knee pain. Engaging
      in exercise using equipment and body weight was associated with higher scores of
      general health. These results indicate that exercise using equipment and body
      weight might have a positive effect on health-related quality of life, but muscle
      strengthening activities are associated with knee pain in older people. 

PMID- 24306458
TI  - Morphological and syntactic awareness in poor comprehenders: another piece of the
      puzzle.
AB  - Poor comprehenders have intact word-reading skills but struggle specifically with
      understanding what they read. We investigated whether two metalinguistic skills,
      morphological and syntactic awareness, are specifically related to poor reading
      comprehension by including separate and combined measures of each. We identified
      poor comprehenders (n = 15) and average comprehenders (n = 15) in Grade 4 who
      were matched on word-reading accuracy and speed, vocabulary, nonverbal cognitive
      ability, and age. The two groups performed comparably on a morphological
      awareness task that involved both morphological and syntactic cues. However, poor
      comprehenders performed less well than average comprehenders on a derivational
      word analogy task in which there was no additional syntactic information, thus
      tapping only morphological awareness, and also less well on a syntactic awareness
      task, in which there were no morphological manipulations. Our task and
      participant-selection process ruled out key nonmetalinguistic sources of
      influence on these tasks. These findings suggest that the relationships among
      reading comprehension, morphological awareness, and syntactic awareness depend on
      the tasks used to measure the latter two. Future research needs to identify
      precisely in which ways these metalinguistic difficulties connect to challenges
      with reading comprehension. 

PMID- 24306459
TI  - Morphological awareness and vocabulary development among kindergartners with
      different ability levels.
AB  - Our goal was to investigate the growth of vocabulary and morphological awareness
      over time in the context of an intervention for kindergartners with different
      ability levels in these skills. Participants in this exploratory study were 108
      children from schools serving socioeconomically disadvantaged neighborhoods.
      Results indicated that children significantly improved their morphological
      awareness skills and vocabulary over a period of 4 months ( eta(p)(2) = .61 for
      morphological awareness and eta(p)(2) = .53 for vocabulary), with the greatest
      gains made by children who were initially low on these measures. Morphological
      awareness and vocabulary skills were reciprocally related; each made a unique
      contribution to growth in the other. The results suggest that it may be
      beneficial to combine instruction in vocabulary and morphological awareness and
      that kindergarten teachers can successfully do so with guidance.

PMID- 24306460
TI  - The effects of a multilinguistic morphological awareness approach for improving
      language and literacy.
AB  - The purpose of this study was to examine the effectiveness of a multilinguistic
      intervention to improve reading and spelling in primary grade students who
      struggle with literacy. Twenty second-grade students with spelling deficits were
      randomly assigned to receive a multilinguistic intervention with a phonological
      and orthographic awareness emphasis, or one with an additional morphological
      awareness focus. The morphological intervention group performed better on
      standardized measures of reading comprehension, and spelling, and on a
      nonstandardized spelling test of morphological patterns. Both groups improved and
      no between-group differences were found on a standardized measure of word
      identification and word attack, as well as on a nonstandardized spelling test of
      orthographic patterns. 

PMID- 24306461
TI  - Putting words to work: effects of morphological instruction on children's
      writing.
AB  - This quasi-experimental study examined effects of a 12-week, teacher-delivered,
      morphologically focused intervention on writing outcomes for fifth-grade U.S.
      students. In order to help students gain control over the morphologically complex
      words that typify academic writing, the intervention called students' attention
      to the morphological structure of words drawn from the district's science
      curriculum, taught morphologically related forms of those words, and provided
      opportunities for students to use morphologically related forms in reading and
      writing. Multilevel model results of posttests showed that, compared to control
      students (n = 75), intervention students (n = 95) included more morphologically
      complex words in a sentence-combining task, whether this was scored by a strict
      (correct spellings only) or lenient (plausible incorrect spellings accepted)
      criterion, and used more morphologically complex words that had been targeted in
      the intervention in their extended written responses. In addition, students with
      lower pretest scores on the sentence-combining measure showed greater
      intervention effects on the sentence-combining measure than did higher performing
      peers. Taken together, these results support the use of morphological instruction
      in the classroom, especially for students who struggle with writing. 

PMID- 24306462
TI  - Dietary effects of phytoecdysones in the leek-moth,Acrolepiopsis assectella Zell.
      (Lepidoptera: Acrolepiidae).
AB  - Incorporation of certain phytoecdysones (ecdysterone, polypodine B, and
      ponasterone A) into a semisynthetic artificial diet induces pathophysiological
      effects in larvae of the leek-moth (Acrolepiopsis assectella Zell.,
      Acrolepiidae). The effects include lethality of the newly hatched, first-instar
      larvae; special ecdysial failures associated with the appearance of larvae with
      two head capsules; and developmental anomalies during metamorphosis. The
      effective range of dietary ecdysteroid, as evaluated by larval mortality, varies
      from 25 to 250 ppm. The EC50 value is 100 ppm for polypodine B and 130 ppm for
      ecdysterone. The dietary effects of the phytoecdysones are similar to the
      previously observed effects caused by the dried flowers, but not leaves, of the
      leek plant. However, the active compound of the leek flowers is a saponin. 

PMID- 24306463
TI  - Food search behavior in arctic charr,Salvelinus alpinus (L.), induced by food
      extracts and amino acids.
AB  - Food search behavior in Arctic charr (Salvelinus alpinus) to extracts of
      granulated food was quantified and compared with the response to solutions of
      amino acid mixtures. The concentration of each of 18 amino acids was analyzed in
      the food extract and similar pure amino acid solutions were prepared. Earlier
      published electrophysiological data and the data of concentrations in the test
      area were used to order the amino acids with respect to their presumed
      contribution to the stimulatory effect of the food extract. The 18 amino acids
      were tested collectively (18 aa) or were divided into two groups, one group
      containing 7 amino acids (7 aa) which was presumed to have a high stimulatory
      effect and the other group containing the remaining 11 amino acids (11 aa). The
      solutions of 7, 11, and 18 aa were stimulatory at concentrations between 2 and 5
      * 10(-6) M, but no significant responses were observed at 2-5 * 10(-9) M. This
      can be compared with the food extract which elicited response at all
      concentrations tested, i.e., the total concentrations of 18 amino acids were 5 *
      10(-9), 5 * 10(-8), 5 * 10(-7), and 5 * 10(-6) M. The response to the 18 aa
      solution was compared with the food extract and was shown to be significantly
      lower at 5 * 10(-9) M but not at 5 * 10(-6) M. These results show that amino
      acids induce food search behavior in Arctic charr, but there are other substances
      which also contribute to the stimulatory effect of the food extract. 

PMID- 24306464
TI  - Flavanone glycosides as oviposition stimulants in a papilionid butterfly,Papilio
      protenor.
AB  - Identification of chemical compounds responsible for the oviposition behavior in
      a Rutaceae feeder,Papilio protenor demetrius, was undertaken with the epicarp of
      sour orange (Citrus natsudaidai) which exhibited potent stimulatory activity as
      did its leaves for egg-laying by the females. The stimulants were present in the
      hydrosoluble fraction, and the kairomonal activity displayed by the peel was
      regarded as originating from the synergistic effect of the total chemical
      complex. One of the active compounds was identified as a flavanone glycoside,
      naringin (naringenin-7beta-neohesperidoside), which, although showing no
      appreciable effectiveness when bioassayed alone, elicited positive response at
      the concentration of 0.2% either when admixed with other unidentified components
      or provided the females had been conditioned with them in advance. Another
      flavanone glycoside, hesperidin (hesperetin-7beta-rutinoside) that was contained
      in a trace amount in the peel also had a positive effect comparable to that of
      naringin under similar conditions, while their corresponding aglycones were less
      active or inactive. In contrast, a flavone glycoside, rhoifolin, coexisting in
      the peel, and some other flavones and flavonols tested as possible candidates for
      oviposition stimulants were all found entirely ineffective. 

PMID- 24306465
TI  - Dynamics of 6-methoxybenzoxazolinone in winter wheat : Effects of photoperiod and
      temperature.
AB  - 6-Methoxybenzoxazolinone (6-MBOA), a compound derivable from some freshly growing
      plants, is known to stimulate reproduction in some mammals and birds. Winter
      wheat was studied under controlled laboratory conditions to determine the effects
      of photoperiod and temperature on derivable 6-MBOA content. Longer photoperiods
      decrease the amount of derivable 6-MBOA per gram of fresh material in 4-day-old
      wheat seedlings. Higher temperatures also decrease the amount of derivable 6-MBOA
      in 4-day-old wheat. 6-MBOA content decreases as the plant ages. Comparisons of
      only the first centimeter above the seed produced the same age-related result. 6
      MBOA is concentrated in the meristematic region with decreasing amounts found in
      higher portions of the plant. Roots from 9-day-old plants contain 6-MBOA.
      Unsprouted wheat seeds contain negligible amounts of 6-MBOA. These results
      demonstrate that environmental variables have a significant effect on derivable 6
      MBOA levels, but that under all the regimes studied, 6-MBOA is present in freshly
      sprouted wheat. 

PMID- 24306466
TI  - Variation of some secondary metabolites in juvenile stages of three plant species
      from tropical rain forest.
AB  - Results from qualitative and quantitative evaluation of some chemical
      constituents, particularly phenols and volatile terpenes, from juvenile stages of
      three primary species belonging to the perennial rain forest are presented. The
      degree of infection and the time of the year were taken into account. TLC, GC,
      and simple chemical methods were used to estimate differences among components.
      Biological assays were conducted to evaluate fungicide potential of the extracts
      from studied plants. In general terms, the results show significant differences
      in the chemical composition of the species studied (Nectandra ambigens, Omphalea
      oleifera, andLicaria alata) related to the time of the year and the degree of
      infection. These differences can be related as well to their intrinsic resistance
      to infection and ability to grow to the adult stage. 

PMID- 24306467
TI  - A reassessment of the binding of napthaleneacetic acid by membrane preparations
      from maize.
AB  - Naphthalene-1-acetic acid (NAA) binding by membrane fractions derived from maize
      has been re-evaluated. Using a computer curve-fitting procedure only one major
      type of NAA binding, in terms of binding affinity, could be identified. Auxins,
      antiauxins and structurally related compounds have been tested for their
      competitive effect on NAA binding and the inhibitor constants for a number of
      these have been determined. Extracts from various plant species have been
      examined for their NAA binding ability, but all showed much less binding than
      maize leaf or coleoptile preparations. The possibility of the NAA binding by
      maize extracts being due to a true hormone receptor is discussed. 

PMID- 24306468
TI  - Chloroplast envelopes as affected by light or dark pretreatment of pea plants.
AB  - Glutaraldehyde fixation in 0.33 M sorbitol without any buffer reveals changes in
      the staining properties of the envelopes of chloroplasts of pea plants kept in
      the light or in the dark prior to fixation. After dark pretreatment the outer
      double membrane of the chloroplast does not adsorb heavy metals, resulting in a
      "white" unstained rim instead of the usual membrane. All other membranes of the
      cell, including chloroplast grana, are not affected and stain normally. Light
      pretreatment of the plants allows the usual staining of the outer membrane of the
      chloroplats. Fixation carried out in the medium usually used to isolate intact
      CO2 fixing chloroplasts (sorbitol+buffer+ions) reverses the above process and
      results in unstained envelopes of chloroplasts from preilluminated leaves, while
      the envelopes of chloroplasts from leaves kept in the dark stain normally.
      Glutaraldehyde-fixed chloroplats isolated from preilluminated leaves show a very
      basic isoelectric point during electrofocusing, while fixed chloroplasts from
      predarkened tissue exhibit an isoelectric point at about pH 7. 

PMID- 24306469
TI  - Ultrastructure and lipid composition of etioplasts in developing dark-grown wheat
      leaves.
AB  - Changes in the ultrastructure and lipid composition of etioplasts have been
      evaluated in three regions from the base to the tip of 8-day-old darkgrown wheat
      leaves and in the upper-2/3 region of etiolated leaves of different ages. In
      developing darkgrown tissues, the main morphological changes that etioplasts
      undergo consist of an increase in the amount of thylakoids which, in the most
      mature etioplasts, align in parallel arrays. Concomitantly, galactolipids and
      sulfolipid form an increasing proportion of the total lipids. Trans-3
      hexadecenoic acid was not detectable in phosphatidylglycerol (PG) of etioplasts
      showing appressed thylakoids isolated from 5-day-old leaves, but was present in
      significant amounts in etioplasts in the basal part of 8-day-ols leaves in which
      membrane appression was barely visible. The proportions of this acid increase as
      etioplasts develop, reaching 25% of the PG fatty acids (1.2% of the total fatty
      acids) in the most differentiated etioplasts. In wheat etioplasts, it appears
      that trans-3-hexadecenoic acid may accumulate in considerable amounts in
      darkgrown tissues and that its accumulation is not directly involved in membrane
      appression. 

PMID- 24306470
TI  - Are polyamines involved in the induction and regulation of the Crassulacean acid
      metabolism?
AB  - Leaves of plants with Crassulacean acid metabolism (CAM) were analyzed for
      variation in the content of polyamines in connection with the metabolism of malic
      acid in the dark and in the light, and with the induction of full-CAM activity.
      Under conditions (long days) resulting in extremely low CAM activity, young
      leaves of K. blossfeldiana have very low content in the polyamine-precursor
      arginine and in putrescine. The content in these two substances was increased
      dramatically by full-CAM induction with short days. During the course of the
      night/day cycle two peaks of putrescine content were observed in leaves of
      Kalanchoe blossfeldiana Poelln. Tom Thumb performing full-CAM operation: a large
      increase occurs toward the end of the day and the first half of the night, and
      its kinetics corresponds to the increase in the rate of malic acid synthesis;
      another peak, very sharp, appears during the first hours of the day, concomitant
      with the time of release of malic acid from the vacuole into the cytoplasm. In
      the case of Bryophyllum daigremontianum Berger similar variations were observed
      for the content in spermidine. These results support the hypothesis that
      polyamines could be involved in countering the tendency toward acidification of
      the cytoplasm at those moments of CAM operation at which the local concentration
      of malic acid is increased (i.e., during active synthesis in the dark and during
      the efflux from the vacuole in the light). 

PMID- 24306471
TI  - Direct turgor pressure measurements in individual leaf cells of Tradescantia
      virginiana.
AB  - The water relations of leaves of Tradescantia virginiana were studied using the
      miniaturized pressure probe (Husken, E. Steudle, Zimmermann, 1978 Plant Physiol.
      61, 158-163). Under well-watered conditions cell turgor pressures, P o, ranged
      from 2 to 8 bar in epidermal cells. In subsidiary cells P o was about 1.5 to 4.5
      bar and in mesophyll cells about 2 to 3.5 bar. From the turgor pressure,
      relaxation induced in individual cells by changing the turgor pressure directly
      by means of the pressure probe, the half-time of water exchange was measured to
      be between 3 and 100 s for the epidermal, subsidiary, and mesophyll cells. The
      volumetric elastic modulus, epsilon, of individual cells was determined by
      changing the cell volume by a defined amount and simultaneously measuring the
      corresponding change in cell turgor pressure. The values for the elastic modulus
      for epidermal, subsidiary, and mesophyll cells are in the range of 40 to 240 bar,
      30 to 200 bar, and 6 to 14 bar, respectively. Using these values, the hydraulic
      conductivity, L p, for the epidermal, subsidiary, and mesophyll cells is
      calculated from the turgor pressure relaxation process (on the basis of the
      thermodynamics of irreversible processes) to be between 1 and 55.10(-7) cm s(-1)
      bar(-1). The data for the volumetric elastic modulus of epidermal and subsidiary
      cells indicate that the corresponding elastic modulus for the guard cells should
      be considerably lower due to the large volume changes of these cells during
      opening or closing. Recalculation of experimental data obtained by K. Raschke
      (1979, Encycl. Plant Physiol. N.S., vol. 7, pp 383-441) on epidermal strips of
      Vicia faba indicates that the elastic modulus of guard cells of V. faba is in the
      order of 40-80 bar for closed stomata. However, with increasing stomatal opening,
      i.e., increasing guard cell volume, epsilon decreases. Therefore, in our opinion
      Raschke's results would indicate a relationship between guard cell volume and
      epsilon which would be inverse to that for plant cells known in the literature.
      epsilon assumes values between 20-40 bar when the guard cell colume is soubled. 

PMID- 24306472
TI  - The initiation of legumin synthesis in immature embryos of Pisum sativum L. grown
      in vivo and in vitro.
AB  - A highly sensitive immunoassay has been used for the detection of a major storage
      protein, legumin, in embryos of Pisum sativum L.; with this technique nanogram
      quantities could be measured. In the two varieties tested, legumin could be
      detected in embryos in vivo, when they had attained a fresh weight of 2.10(-3) g
      and 3.10(-3) g, respectively. Contrary to earlier claims, embryos cultured in
      vitro were shown to be capable of initiating legumin synthesis. This capacity to
      initiate legumin synthesis was confirmed by two-dimensional isoelectric focusing
      electrophoresis and fluorography; embryos harvested before initiation of legumin
      synthesis and cultured in radioactive medium were shown to have synthesized
      legumin subunits. The amounts of legumin and total protein synthesized per unit
      fresh weight were consistently greater in vitro than in equivalent embryos grown
      in vivo. 

PMID- 24306473
TI  - Formation of (n-9) and (n-7) cis-monounsaturated fatty acids in seeds of higher
      plants.
AB  - The relative abundance of (n-9) and (n-7) isomers in the monounsaturated fatty
      acids of seed lipids has been determined for selected plants in order to assess
      the biosynthetic reactions involved in their formation. Delta9 Desaturation of
      stearic acid to (n-9) octadecenoic acid is almost exclusively operative in the
      formation of monounsaturated fatty acids in the seeds of Helianthus annuus,
      Glycine max and Brassica napus, cv. Quinta and Erglu, in which chain elongation
      of monounsaturated fatty acids terminates at the level of an 18 carbon chain.
      Delta9 Desaturation of palmitic acid is a minor yet significant pathway in the
      seeds of Sinapis alba and Brassica napus, cv. Rapol and Tira, in which chain
      elongation of monounsaturated fatty acids occurs extensively beyond the 18 carbon
      chain. In each of these seeds, both (n-9) and (n-7) octadecenoic acids formed are
      subsequently elongated to icosenoic acids. However, elongation of the (n-7)
      isomer is terminated at the level of a 20 carbon chain, whereas the (n-9)
      icosenoic acid is selectively elongated to docosenoic acid and even up to
      tetracosenoic acid in Sinapis alba. Delta9 Desaturation of palmitic acid followed
      by elongation to (n-7) octadecenoic acid occurs to a minor extent in the seeds of
      Tropaeolum majus. Only the (n-9) octadecenoic acid, and not its (n-7) isomer, is
      elongated to icosenoic and docosenoic acids. 

PMID- 24306474
TI  - Phospholipid composition and fatty acid desaturation in the roots of rye during
      acclimatization of low temperature : Positional analysis of fatty acids.
AB  - When the roots of rye plants grown at 20 degrees C were cooled to 8 degrees C the
      concentration of phospholipid in them more than doubled over a 7 d period in
      comparison with that in roots remaining at 20 degrees C. The relative abundance
      of lecithin (PC) declined while that of phosphatidyl ethanolamine (PE) increased;
      this change was completed after 2 d cooling. Labelling with (32)P suggested that
      turnover of phospholipids may be inhibited by low temperature. Acyl lipids
      contained an increased proportion of linolenic acid (18:3) and reduced proportion
      of linoleic acid (18:2) when roots were cooled at 8 degrees C for 7 d. The ratio
      of these acids is a relatively more sensitive indicator of desaturation than is
      the double bond index. Cooling brought about no change in the abundance of the
      principal saturated acid, palmitic (16:0). In the first 3 days of cooling PC and
      PE desaturated markedly while there was no change in galactosyl and neutral
      lipids. Desaturation did not appear to be greatly sensitive to the concentration
      of dissolved O2 and was only partly inhibited in 8 degrees C solutions where the
      oxygen concentration was lowered to 0.5-2.0%. Positional analysis of acyl chains
      in PC and PE showed that more than 90% of all 16:0 is associated with position I
      while 65% of the 18:2+18:3 is associated with position II. When roots are cooled
      the abundance of 18:3 increases in both chains but the relative distribution of
      saturated and unsaturated fatty acids remains constant in positions I and II. At
      both 20 degrees C and 8 degrees C there is a high probability that a saturated
      chain in position I will be paired with the polyunsaturated one in position II. 

PMID- 24306475
TI  - Zeatin-9-glucoside, a major endogenous cytokinin of Vinca rosea L. crown gall
      tissue.
AB  - Cultured crown gall tissue of Vinca rosea L. was found to contain, in addition to
      the previously reported cytokinins zeatin, zeatin riboside, and the 0-glucosides
      of these two compounds, relatively high levels of zeatin-9-D-glucopyranoside.
      This is the first conclusive identification of an endogenous cytokinin 9
      glucoside. 

PMID- 24306476
TI  - Isozymes of the glycolytic and pentose-phosphate pathways in storage tissues of
      different oilseeds.
AB  - Isozymes of hexose-phosphate isomerase (HPI; EC 5.3.1.9), pyruvate kinase (PK; EC
      2.7.1.40) and 6-phosphogluconate dehydrogenase (6PGDH; EC 1.1.1.44) have been
      detected in the developing cotyledons of soybean (Glycine max (L.) Merr.),
      safflower (Carthamnus tinctorius L.) and sunflower (Helianthus annuus L.). In
      each seed there are two isozymes each of PK and HPI. The isozyme patterns of
      6PGDH are more complex: soybean has two forms of the enzyme, safflower three, and
      sunflower six. In each tissue, at least 25% of the activity of each of the three
      enzymes is in the plastids. This supports the proposal that the glycolytic and
      pentose-phosphate pathways are operating in the plastids and that the plastids
      are the site of long-chain fatty-acid biosynthesis in developing oilseeds. 

PMID- 24306477
TI  - Partial characterization of two stable auxotrophic cell strains of Datura innoxia
      Mill.
AB  - A growth analysis of several presumptive "leaky" auxotrophs from Datura innoxia
      suspension cultures led to the discovery of an adenine-requiring cultures led to
      the discovery of an adenine-requiring cell strain (Ad1). Both Ad1 and Pn1, a
      pantothenate-requiring strain isolated earlier from these cultures, still require
      either adenine or pantothenate for growth after more than one year in culture.
      Attempts to select prototrophic revertants have failed. Ad 1 also grew well in a
      medium containing either 5-aminoimidazole-4-carboxamide ribotide or inosine
      instead of adenine; Pn 1 with pantoic acid alone but not at all in the presence
      of beta-alanine or alpha-ketoisovalerate alone instead of pantothenate. Pn 1
      cells starved of pantothenate for up to 4d and Ad1 of adenine for 10d or more
      resumed growth when transferred to appropriately supplemented media. Wild-type
      Datura cells grown on unsupplemented medium would not crossfeed the required
      nutrients to the auxotrophs. The starvation and cross-feeding experiment showed
      that both auxotrophs could be used in reconstruction experiments to develop
      enrichment-selection techniques for the isolation of more auxotrophs. 

PMID- 24306478
TI  - Effects of pH and other factors on the phosphate dependence of photosynthesis in
      spinach chloroplasts.
AB  - Chloroplast stromal volume and pH influenced the phosphate (Pi)-dependence of
      photosynthesis of spinach (Spinacia oleracea L.) chloroplasts. Decreasing the
      sorbitol concentration in the reaction mixture from 0.35 to 0.25 M, or decreasing
      the external pH from 8.3 to 7.3, extended the induction period of photosynthesis
      and decreased both the optimal [Pi] and the minimal [Pi] required to inhibit O2
      evolution completely. At least part of the effect of external pH was attributable
      to changes in stromal pH on the basis of effects of NH4Cl and sodium acetate at a
      constant external pH. When the external pH was increased from 7.3 to 8.3, the
      stromal pH changed only about 0.6 pH units. Hence, the pH gradient across the
      envelope was diminished and the efflux of phosphoglycerate relative to
      dihydroxyacetone phosphate was enhanced.Calvin-cycle activity, varied with light
      intesity or electron transport inhibitors, affected the rate of photosynthesis
      but not the induction period or the Pi optimum for photosynthesis. Relatively low
      Calvin-cycle activity was apparently sufficient to fill metabolite pools and thus
      terminate the induction period. The results indicate that pH does not affect the
      Pi dependence of photosynthesis by reducing Calvin-cycle activity. Rather, it is
      postulated that at low stromal pH, larger metabolic pools are required to
      maintain maximum rates of photosynthesis because of changes in substrate affinity
      of some Calvin-cycle enzymes. Consequently, chloroplast photosynthesis would be
      more sensitive to exogenous Pi. 

PMID- 24306479
TI  - Isolation of a cell-fusion hormone from Griffithsia pacifica kylin, a red alga.
AB  - Filaments of Griffithsia pacifica replace dead cells by the process of cell
      repair. When an intercalary cell is killed, but its cell wall remains intact
      holding the two halves of the plant together, the cell above it produces a repair
      rhizoid cell; the cell below it produces a specialized, rhizoid-like repair shoot
      cell. The repair rhizoid and shoot grow towards each other, meet, and fuse to
      form a single shoot cell. Evidence from observations of cell repair in vivo has
      indicated that the repair rhizoid produces a hormone or hormones which induce the
      production of the repair shoot, maintain the rhizoid-like morphology and growth
      of the repair shoot, and attract it to the repair rhizoid for fusion. This
      hormone has been named rhodomorphin. Using an artificial cell-fusion system we
      show that repair rhizoids and normal rhizoids, but no shoot cell, can induce
      decapitated filaments to form repair shoot cells. Decapitated filaments form
      repair shoot cells only when they are exposed to the hormone within 4-6 h after
      decapitation; after this time they lose their sensitivity to the hormone. A
      method has been developed for isolating, and assaying for, the cell-fusion
      hormone. Rhodomorphin retains its activity for several days at room temperature
      and for at least two years at-16 degrees  C. 

PMID- 24306480
TI  - Composition, ultrastructure and function of the cutin- and suberin-containing
      layers in the leaf, fruit peel, juice-sac and inner seed coat of grapefruit
      (Citrus paradisi Macfed.).
AB  - Cutin and suberin polymers from various anatomical regions of grapefruit were
      analyzed chemically and ultrastructurally. The leaf, fruit peel and juice-sac
      showed an amorphous cuticular layer. The cutin in the leaf was composed of 10,16
      dihydroxy C16 acid and its positional isomers as the major monomers whereas 16
      hydroxy-10-oxo C16 acid was a major component in the fruit peel. Juice-sac cutin,
      on the other hand, contained the dihydroxy C16 acids, hydroxyoxo C16 acids,
      hydroxyepoxy C18 acids and trihydroxy C18 acids. Ultrastructural examination of
      the inner seed coat showed that an amorphous cuticular layer encircled the entire
      seed except in the chalazal region which showed several layers of cells with
      lamellar suberin structure throughout the cell walls. Consistent with the
      ultrastructural assignment, the compositions of the aliphatic components of the
      polymers from the chalazal region and the non-chalazal region indicated the
      presence of suberin and cutin, respectively. The aliphatic portion of the polymer
      from the chalazal region of the inner seed coat contained C16, C18:1, C22 and C24
      omega-hydroxy acids (46% combined total) and the corresponding dicarboxylic acids
      (43%) as the major components. omega-Hydroxy-9,10-epoxy C18 acids and 9,10,18
      trihydroxy C18 acids were the major components (77%) of the polymer from the non
      chalazal portion of the inner seed coat. The main portion and the chalazal region
      of the inner seed coat yielded 17 and 342 MUg/cm(2) of aliphatic monomers,
      respectively, and the diffusion resistance of these two portions of the inner
      seed coat were 62 and 192 sec/cm, respectively. The inner seed coat was shown to
      be the major moisture diffusion barrier influencing imbibition and germination. 

PMID- 24306481
TI  - Erratum.

PMID- 24306483
TI  - Comparison of single cell culture derived Solanum tuberosum L. plants and a model
      for their application in breeding programs.
AB  - The techniques of microspore and protoplast regeneration starting from dihaploid
      Solanum tuberosum plants has been improved to such an extent that the production
      of more than 2000 microspore derived A1 plant lines and of several hundred
      protoplast derived plantlets has become possible. Further, from the dihaploid
      Solanum species S. phureja the regeneration of microspores to plants, and from
      the species S. infundibuliforme, S. sparsipilum and S. tarijense the regeneration
      of protoplasts to calluses, has been achieved. The plants descending from the two
      single cell culture systems are compared with reference to phenotypic markers and
      economic qualities. Some principles characteristic for either microspore or
      protoplast derived plants are examined and their significance is discussed. The
      results are compiled into an extended analytical synthetic breeding scheme based
      on a stepwise reduction of the autotetraploid to the monohaploid level and a
      subsequent controlled combination to a new synthetic completely heterozygous
      tetraploid potato. 

PMID- 24306484
TI  - The effects of selection for different combinations of weights at two ages on the
      growth curve of mice.
AB  - The weights of mice in lines selected for different combinations of high and low
      body weights at 5 and at 10 weeks of age were recorded from 3 to 21 weeks of age.
      The average growth curve for each line was computed using the Gompertz function.
      The growth curves of lines selected for high or low weight at a single age (ST
      lines) showed large differences in estimates of mature size and small differences
      in estimates of maturing rate, i.e. of the relative rate of growth to maturity.
      The growth curves of lines selected by independent culling for divergent
      combinations of deviations of opposite sign in 5- and 10-week weights (ICL lines)
      showed little difference in estimates of mature size and a large difference in
      estimates of maturing rate. The growth curves of lines selected by index for
      divergence in 5-week weight with no change in 10-week-weight or for divergence in
      10-week-weight with no change in 5-week weight showed large differences in
      estimates of mature size and large differences in estimates of the maturing rate.
      The relationship between mature size and maturing rate was affected in different
      ways by the three types of selection. 

PMID- 24306485
TI  - Stimulation of embryogenesis and haploid production in Brassica campestris anther
      cultures by elevated temperature treatments.
AB  - Culture of Brassica campestris anthers at 35 degrees C for one or three days
      prior to culture at 25 degrees C significantly stimulated the yield of microspore
      derived embryos. More than 100 plants were regenerated from cultured embryos and
      haploids were identified amongst them. The haploid frequency was greater than 70%
      if all small-flowered sterile plants were considered to be haploid. The yield of
      microspore-derived plants in B. campestris is approaching the level where anther
      culture may be utilized as a practical breeding tool. 

PMID- 24306482
TI  - Higher plasma CXCL12 levels predict incident myocardial infarction and death in
      chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort
      study.
AB  - AIMS: Genome-wide association studies revealed an association between a locus at
      10q11, downstream from CXCL12, and myocardial infarction (MI). However, the
      relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors,
      incident MI, and death is unknown. METHODS AND RESULTS: We analysed study-entry
      plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency
      Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in
      chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI
      or death. Plasma CXCL12 levels were positively associated with several
      cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia),
      lower estimated glomerular filtration rate (eGFR), and higher inflammatory
      cytokine levels (P < 0.05). In fully adjusted models, higher study-entry CXCL12
      was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence
      interval 1.14, 1.33, P < 0.001) for one standard deviation (SD) increase in
      CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI
      (1.26; 1.09,1.45, P < 0.001), death (1.20; 1.09,1.33, P < 0.001), and combined
      MI/death (1.23; 1.13-1.34, P < 0.001) adjusting for demographic factors, known
      CVD risk factors, and inflammatory markers and remained significant for MI (1.19;
      1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after
      further controlling for eGFR and urinary albumin:creatinine ratio. CONCLUSIONS:
      In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent
      CVD as well as the hazard of incident MI and death. Further studies are required
      to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a
      tool for genomic and therapeutic trials.

PMID- 24306486
TI  - Selection of potato callus for resistance to culture filtrates of Phytophthora
      infestans and regeneration of resistant plants.
AB  - Dihaploid calli from Solanum tuberosum were selected, which were resistant to the
      culture filtrate of Phytophthora infestans. Each of the resistant calli was
      resistant to all four pathotypes of Phytophthora used in these experiments. The
      resistance was not lost through regeneration and the induction of new callus. 

PMID- 24306487
TI  - The chromosomal location of peroxidase isozymes of the wheat kernel.
AB  - The analysis of the individual parts of the Triticum aestivum L. kernel yields a
      total of 11 peroxidase isozymes: m, n, a, c, d1, d, d2, e, f, g and h (in order
      from faster to slower migration). Isozymes a, c and d are found in the endosperm
      (Ed) and seed coats (C), while m, n, d1, d2, e, f, g and h are peculiar to the
      embryo and scutellum (E + S). The use of the nullitetrasomic and ditellosomic
      series of 'Chinese Spring' wheat allows peroxidase isozymes to be associated with
      specific chromosome arms. Isozymes a, c and d (Ed) are associated with chromosome
      arms 7D(S), 4B(L) and 7A(S); whereas isozymes m, d2, e and f are associated with
      chromosome arms 3D(S), 3B(L), 3D(L) and 3D(L), respecitvely. Thus, the E + S
      isozymes are associated with homoeology group 3 and the Ed isozymes with
      homoeology groups 7 (a and d isozymes) or 4 (c isozymes). 

PMID- 24306488
TI  - Combining ability analysis over F1-F 5 generations in diallel crosses of bread
      wheat.
AB  - Combining ability studies for grain yield and its primary component traits in
      diallel crosses involving seven diverse wheat cultivars of bread wheat (Triticum
      aestivum L.) over generations F1-F5 are reported. The general and specific
      combining ability variances were significant in all generations for all the
      traits except specific combining ability variance for number of spikes per plant
      in the F5. The ratio of general to specific combining ability variances was
      significant for all the traits except grain yield in all the generations. This
      indicated an equal role of additive and non-additive gene effects in the
      inheritance of grain yield, and the predominance of the former for its component
      traits. The presence of significant specific combining ability variances in even
      the advanced generations may be the result of an additive x additive type of
      epistasis or evolutionary divergence among progenies in the same parental array.
      The relative breeding values of the parental varieties, as indicated by their
      general combining ability effects, did not vary much over the generations. The
      cheap and reliable procedure observed for making the choice of parents, selecting
      hybrids and predicting advanced generation (F5) bulk hybrid performance was the
      determination of breeding values of the parents on the relative performance of
      their F2 progeny bulks. 

PMID- 24306489
TI  - An efficient plating system for rapid isolation of mutants from plant cell
      suspensions.
AB  - A plating system for cell suspensions of soybean, SB-1, (Glycine max L. cv.
      'Mandarin') and Datura innoxia D.I. (Mill) was developed using feeder cells. The
      characteristics of the system are: a) the efficiency of plating (EOP) is high
      (0.5-0.6), b) over a range of 10-300 plated clumps the EOP is constant, c) the
      growth rate of plated cells resembles that of suspension cultures (generation
      time 24 hr.). Clumps with few or with many cells have similar plating
      efficiencies.Employing the plating system, a mutant resistant to 8 azaguanine
      (8AG) was isolated from SB-1 in 7 days and purified and tested within an
      additional 3 weeks. Feeder plates were used to selectively re-isolate 8 AG
      resistant and maltose utilizing mutants from a 1000-fold excess of wild type
      cells.The plating technique also can be utilized to isolate auxotrophic mutants
      since free amino acids are not produced by the feeder suspension. Other
      applications of this plating technique are discussed. 

PMID- 24306490
TI  - Peroxidase activities in relation to plant height and grain weight in bread wheat
      (Triticum aestivum L.).
AB  - The relationship of peroxidase activity with plant height and grain weight has
      been studied in seven different varieties of bread wheat belonging to diverse
      genotypes, and their F1 crosses. The association between plant height and
      peroxidase activity was highly significant and negative. Based on the similarity
      index values of peroxidase isoenzymes, the seven wheat genotypes could be
      classified into two groups: the first group consisting of triple and quadruple
      dwarf varieties and the other of tall, single and double dwarf. A negative
      correlation between peroxidase activity and grain weight was also observed.
      However, the results of this study indicate a possibility of developing a dwarf
      plant type with low peroxidase activity and well filled grains. 

PMID- 24306491
TI  - Structure, photoluminescent and cathodoluminescent properties of a rare-earth
      free red emitting beta-Zn3B2O6:Mn2+ phosphor.
AB  - A rare-earth free red emitting beta-Zn3B2O6:Mn(2+) phosphor was prepared by a
      solid-state reaction method. The crystal structure, photoluminescent and
      cathodoluminescent properties of beta-Zn3B2O6:Mn(2+) were systematically
      investigated. The absorption and photoluminescence excitation spectra confirm
      that beta-Zn3B2O6:Mn(2+) matches the UV LED chip. Under UV light and low-voltage
      electron beam excitations, an interesting orange-red emission band centered at
      ~600 nm of Mn(2+) at the tetrahedral Zn(2+) sites is observed. Besides, the
      unusual red shift with increasing Mn(2+) content is also found and contributed to
      an exchange interaction between Mn(2+). In addition, under low-voltage
      excitation, beta-Zn3B2O6:Mn(2+) exhibits higher color purity of 98.1% than that
      of the commercial ZnS:Ag,Cd yellow phosphor and reported ZnGeN2:Mn(2+) orange
      phosphor, which indicated the beta-Zn3B2O6:Mn(2+) has a patenting application in
      FEDs. 

PMID- 24306492
TI  - Ion Torrent sequencing for conducting genome-wide scans for mutation mapping
      analysis.
AB  - Mutation mapping in mice can be readily accomplished by genome wide segregation
      analysis of polymorphic DNA markers. In this study, we showed the efficacy of Ion
      Torrent next generation sequencing for conducting genome-wide scans to map and
      identify a mutation causing congenital heart disease in a mouse mutant, Bishu,
      recovered from a mouse mutagenesis screen. The Bishu mutant line generated in a
      C57BL/6J (B6) background was intercrossed with another inbred strain, C57BL/10J
      (B10), and the resulting B6/B10 hybrid offspring were intercrossed to generate
      mutants used for the mapping analysis. For each mutant sample, a panel of 123
      B6/B10 polymorphic SNPs distributed throughout the mouse genome was PCR
      amplified, bar coded, and then pooled to generate a single library used for Ion
      Torrent sequencing. Sequencing carried out using the 314 chip yielded >600,000
      usable reads. These were aligned and mapped using a custom bioinformatics
      pipeline. Each SNP was sequenced to a depth >500*, allowing accurate automated
      calling of the B6/B10 genotypes. This analysis mapped the mutation in Bishu to an
      interval on the proximal region of mouse chromosome 4. This was confirmed by
      parallel capillary sequencing of the 123 polymorphic SNPs. Further analysis of
      genes in the map interval identified a splicing mutation in Dnaic1(c.204+1G>A),
      an intermediate chain dynein, as the disease causing mutation in Bishu. Overall,
      our experience shows Ion Torrent amplicon sequencing is high throughput and cost
      effective for conducting genome-wide mapping analysis and is easily scalable for
      other high volume genotyping analyses.

PMID- 24306493
TI  - Characterization and RNA-seq analysis of underperformer, an activation-tagged
      potato mutant.
AB  - The potato cv. Bintje and a Bintje activation-tagged mutant, underperformer (up)
      were compared. Mutant up plants grown in vitro were dwarf, with abundant axillary
      shoot growth, greater tuber yield, altered tuber traits and early senescence
      compared to wild type. Under in vivo conditions, the dwarf and early senescence
      phenotypes of the mutant remained, but the up plants exhibited a lower tuber
      yield and fewer axillary shoots compared to wild type. Southern blot analyses
      indicated a single T-DNA insertion in the mutant, located on chromosome 10.
      Initial PCR-based gene expression studies indicated transcriptional
      activation/repression of several genes in the mutant flanking the insertion. The
      gene immediately flanking the right border of the T-DNA insertion, which encoded
      an uncharacterized Broad complex, Tramtrac, Bric-a-brac; also known as Pox virus
      and Zinc finger (BTB/POZ) domain-containing protein (StBTB/POZ1) containing an
      Armadillo repeat region, was up-regulated in the mutant. Global gene expression
      comparisons between Bintje and up using RNA-seq on leaves from 60 day-old plants
      revealed a dataset of over 1,600 differentially expressed genes. Gene expression
      analyses suggested a variety of biological processes and pathways were modified
      in the mutant, including carbohydrate and lipid metabolism, cell division and
      cell cycle activity, biotic and abiotic stress responses, and proteolysis.

PMID- 24306495
TI  - Intensive visible-light photoactivity of Bi- and Fe-containing pyrochlore
      nanoparticles.
AB  - Bi-Fe-Nb-O pyrochlore nanoparticles were synthesized by a facile coprecipitation
      reaction. They exhibit intense visible-light absorption due to a narrow band gap
      and high visible-light photocatalytic activity for degradation of methyl orange. 

PMID- 24306494
TI  - Increase in transcript accumulation of Psy1 and e-Lcy genes in grain development
      is associated with differences in seed carotenoid content between durum wheat and
      tritordeum.
AB  - Carotenoid rich diets have been associated with lower risk of certain diseases.
      The great importance of cereals in human diet has directed breeding programs
      towards carotenoid enhancement to alleviate these deficiencies in developing
      countries and to offer new functional foods in the developed ones. The new cereal
      tritordeum (*Tritordeum Ascherson et Graebener) derived from durum wheat
      (Triticum turgidum ssp. durum) and the wild barley Hordeum chilense, naturally
      presents carotenoid levels 5-8 times higher than those of durum wheat. The
      improvement of tritordeum properties as a new functional food requires the
      elucidation of biosynthetic steps for carotenoid accumulation in seeds that
      differ from durum wheat. In this work expression patterns of nine genes from the
      isoprenoid and carotenoid biosynthetic pathways were monitored during grain
      development in durum wheat and tritordeum. Additionally, a fine identification
      and quantification of pigments (chlorophylls and carotenoids) during grain
      development and in mature seeds has been addressed. Transcript levels of Psy1,
      Psy2, Zds, e-Lcy and b-Lcy were found to correlate to carotenoid content in
      mature grains. The specific activation of the homeologous genes Psy1, e-Lcy from
      H. chilense and the high lutein esterification found in tritordeum may serve to
      explain the differences with durum wheat in carotenoid accumulation. 

PMID- 24306496
TI  - Checklist for standardized reporting of drug-drug interaction management
      guidelines.
AB  - PURPOSE: Inconsistencies and omissions in drug-drug interaction (DDI) management
      guidelines may lead to harm and suboptimal therapy. The purpose of this study was
      to define a checklist for DDI management guidelines to help developers produce
      high-quality guidelines that will support healthcare providers in clinical
      practice. METHODS: We carried out a two-round Delphi process with an
      international panel of healthcare providers, most of whom are pharmacists
      involved in providing DDI information, in order to select those items that should
      be addressed in DDI management guidelines (including grading systems that could
      be used). RESULTS: Twenty-three panellists reached consensus on 19 items in two
      main domains. These were consolidated into a checklist of 15 elements for
      standardized reporting in management guidelines. For each element a description
      is provided to specify what information should be documented in that specific
      element. CONCLUSIONS: It was possible to reach a broad consensus on which
      relevant items should be included in a checklist for the development of DDI
      management guidelines.

PMID- 24306497
TI  - On the possible interaction between vaccines and drugs.

PMID- 24306499
TI  - Effects of pH on the kinetics of redox reactions in and around the cytochromebf
      complex in an isolated system.
AB  - Rate-coefficients describing the electron transfer reactions between P700 and
      plastocyanin, between cytochromef in cytochromebf complexes and plastocyanin, and
      between decyl plastoquinol and cytochromebf complexes were determined as a
      function of pH in the range 4-10 from flash-induced absorbancy changes at four
      wavelengths. The reactions between P700 and plastocyanin, and between cytochromef
      and plastocyanin were optimised when there was electrostatic interaction between
      ionised acidic groups in plastocyanin with a pKa of 4.3-4.7 and ionised basic
      constituents in P700 (assumed to be in the PSI-F subunit) and in cytochromef,
      with a pKb of 8.9-9.4. The basic groups are thought to be lysine rather than
      arginine. This mechanism agrees with that inferred from effects of ionic strength
      changes on rate-coefficients. The relation between the second-order rate
      coefficient for decyl plastoquinol oxidation by thebf complex and pH was
      characterised by a pKa of 6.1. This is interpreted as showing that the anion
      radical form of that quinol, which has a pKa of 6, and which becomes
      progressively protonated when pH is changed from 7 to 5, is essential to reduce
      cytochromeb-563 (low potential) during quinol oxidation. Above pH 9, permanent
      effects were observed on this rate-coefficient, which were absent in the
      reactions between P700, plastocyanin and cytochromef. 

PMID- 24306498
TI  - Regulation and possible function of the violaxanthin cycle.
AB  - This paper discusses biochemical and regulatory aspects of the violaxanthin cycle
      as well as its possible role in photoprotection. The violaxanthin cycle responds
      to environmental conditions in the short-term and long-term by adjusting rates of
      pigment conversions and pool sizes of cycle pigments, respectively. Experimental
      evidence indicating a relationship between zeaxanthin formation and non
      photochemical energy dissipation is reviewed. Zeaxanthin-associated energy
      dissipation appears to be dependent on transthylakoid DeltapH. The involvement of
      light-harvesting complex II in this quenching process is indicated by several
      studies. The current hypotheses on the underlying mechanism of zeaxanthin
      dependent quenching are alterations of membrane properties, including
      conformational changes of the light-harvesting complex II, and singlet-singlet
      energy transfer from chlorophyll to zeaxanthin. 

PMID- 24306500
TI  - A robust protocol for site-directed mutagenesis of the D1 protein inChlamydomonas
      reinhardtii: A PCR-splicedpsbA gene in a plasmid conferring spectinomycin
      resistance was introduced into apsbA deletion strain.
AB  - In this paper, we describe a protocol to obtain a site-directed mutants in
      thepsbA gene ofChlamydomonas reinhardtii, which overcomes several drawbacks of
      previous protocols, and makes it possible to generate a mutant within a month.
      Since the large size of the gene, and the presence of four large introns has made
      molecular genetics of thepsbA gene rather unwieldy, we have spliced all of the
      exons of thepsbA gene by PCR to facilitate genetic manipulation and sequencing of
      the gene. The resultant construct (plasmid pBA153, with several unique
      restriction sites introduced at exon boundaries) carried 1.2 and 1.8 kb intact
      sequences from the 5'- and 3'-flanking regions, respectively. The plasmid was
      used to transform a D1-deletion mutant and was found to complement the deletion
      and restore photosynthetic activity. In addition, a bacterialaadA gene conferring
      spectinomycin resistance (spe (r)) was inserted downstream of the intron-freepsbA
      gene, to give construct pBA155. This allowed selection of mutant strains
      deficient in photosynthesis by using spectinomycin resistance, and eliminated the
      possibility of selection for revertant strains which is a consequence of having
      to use photosynthetic activity as a selection pressure. Finally, pBA155 was used
      to construct pBA157, in which additional restriction sites were inserted to
      facilitate cassette mutagenesis for generation of mutations in spans thought to
      be involved in donor-side interactions. AllpsbA deletion strains transformed with
      intron-freepsbA-aadA constructs encoding the wild-type D1 sequence, and screened
      on spectinomycin plates for thespe (r) phenotype, were able to grow
      photosynthetically, and all showed identical kinetics for electron transfer from
      primary (QA) to secondary quinone (QB) in Photosystem II, as assayed by the decay
      of the high fluorescence yield on oxidation of the reduced primary acceptor (QA (
      )). 

PMID- 24306501
TI  - Light/dark modulation of phosphoenolpyruvate carboxylase in C3 and C 4 species.
AB  - In this report, the effects of light on the activity and allosteric properties of
      phosphoenolpyruvate (PEP) carboxylase were examined in newly matured leaves of
      several C3 and C4 species. Illumination of previously darkened leaves increased
      the enzyme activity 1.1 to 1.3 fold in C3 species and 1.4 to 2.3 fold in C4
      species, when assayed under suboptimal conditions (pH 7) without allosteric
      effectors. The sensitivities of PEP carboxylase to the allosteric effectors
      malate and glucose-6-phosphate were markedly different between C3 and C4 species.
      In the presence of 5 mM malate, the activity of the enzyme extracted from
      illuminated leaves was 3 to 10 fold higher than that from darkened leaves in C4
      species due to reduced malate inhibition of the enzyme from illuminated leaves,
      whereas it increased only slightly in C3 species. The Ki(malate) for the enzyme
      increased about 3 fold by illumination in C4 species, but increased only slightly
      in C3 species. Also, the addition of the positive effector glucose-6-phosphate
      provided much greater protection against malate inhibition of the enzyme from C4
      species than C3 species. Feeding nitrate to excised leaves of nitrogen deficient
      plants enhanced the degree of light activation of PEP carboxylase in the C4
      species maize, but had little or no effect in the C3 species wheat. These results
      suggest that post-translational modification by light affects the activity and
      allosteric properties of PEP carboxylase to a much greater extend in C4 than in
      C3 species. 

PMID- 24306502
TI  - Photosynthetic performance and fluorescence in relation to antenna size and
      absorption cross-sections in rye and barley grown under normal and intermittent
      light conditions.
AB  - The size of the Photosystem II light harvesting antenna and the absorption cross
      sections of PS I (sigmaPSI) and PS II (sigmaPSII) were examined in relation to
      photosynthetic performance fluorescence. Wild-type (WT) rye (Secale cereale) and
      barley (Hordeurn vulgare) as well as the barley chlorophyllb-less chlorina F2
      mutant were grown under control and intermittent light (IML) conditions.
      (sigmaPSII) in control barley F2 was similar to IML grown WT rye and barley,
      which, in turn was 2.5 to 3.5 times smaller than for control WT plants. In
      contrast, sigmaPSI was similar for all control plants. This was 2.5 to 4 times
      larger than for IML-grown WT plants. IML-grown barley mutant plants had the
      smallest absorption cross-sections. Photosynthetic light response curves revealed
      that the barley chlorina F2-mutant had rates of oxygen evolution on a per leaf
      area basis that were only slightly lower than control WT rye and barley while IML
      grown plants had strongly reduced photosynthetic performance. Convexity (Theta)
      for control barley chlorina F2-mutants was equal to the WT controls (0.6-0.7),
      while all IML-grown plants had a Theta of 0. This indicates that, in contrast to
      control barley mutants, IML-plants were limited by PS II turn-over rates at all
      irradiances. However, on a per leaf Chl-basis the IML-grown plants exhibited the
      highest photosynthetic rates. Thus, the comparatively poor photosynthetic rates
      for IML-grown plants on a per leaf area basis were not due to less efficient
      photosynthetic reaction centers, but may rather be due to an increased limitation
      from PS II turn-over and a reduction in the number of reaction centers per leaf
      area. 

PMID- 24306503
TI  - Triplet energy transfer between bacteriochlorophyll and carotenoids in B850 light
      harvesting complexes ofRhodobacter sphaeroides R-26.1.
AB  - The build-up and decay of bacteriochlorophyll (BChl) and carotenoid triplet
      states were studied by flash absorption spectroscopy in (a) the B800-850 antenna
      complex ofRhodobacter (Rb.)sphaeroides wild type strain 2.4.1, (b) theRb.
      sphaeroides R-26.1 B850 light-harvesting complex incorporated with spheroidene,
      (c) the B850 complex incorporated with 3,4-dihydrospheroidene, (d) the B850
      complex incorporated with 3,4,5,6-tetrahydrospheroidene and (e) theRb.
      sphaeroides R-26.1 B850 complex lacking carotenoids. Steady state absorption and
      circular dichroism spectroscopy were used to evaluate the structural integrity of
      the complexes. The transient data were fit according to either single or double
      exponential rate expressions. The triplet lifetimes of the carotenoids were
      observed to be 7.0+/-0.1 MUs for the B800-850 complex, 14+/-2 MUs for the B850
      complex incorporated with spheroidene, and 19+/-2 MUs for the B850 complex
      incorporated with 3,4-dihydrospheroidene. The BChl triplet lifetime in the B850
      complex was 80+/-5 MUs. No quenching of BChl triplet states was seen in the B850
      complex incorporated with 3,4,5,6-tetrahydrospheroidene. For the B850 complex
      incorporated with spheroidene and with 3,4-dihydrospheroidene, the percentage of
      BChl quenched by carotenoids was found to be related to the percentage of
      carotenoid incorporation. The triplet energy transfer efficiencies are compared
      to the values for singlet energy transfer measured previously (Frank et al.
      (1993) Photochem. Photobiol. 57: 49-55) on the same samples. These studies
      provide a systematic approach to exploring the effects of state energies and
      lifetimes on energy transfer between BChls and carotenoids in vivo. 

PMID- 24306504
TI  - Prevalence and patterns of substance use among early adolescents.
AB  - Prevalence and patterns of substance use are described for a sample of 105 San
      Francisco East Bay adolescents (age 14). Data are compared with national
      statistics on substance use among high school seniors. While alcohol use appeared
      comparable to the national statistics, tobacco use was less prevalent among this
      younger western sample. Despite the differences in ages, use of marijuana,
      cocaine, and hallucinogens was similar to national high school prevalence; use of
      other "harder" drugs was more extensive among the older, national sample.
      Contrary to typical findings, males and females were not found to differ in
      frequency or extent of substance use; females appeared somewhat more involved in
      substance use at this early age. Initiation of substance use occurred at early
      grade levels, suggesting that intervention efforts should begin prior to junior
      high, perhaps as early as fourth or fifth grade. 

PMID- 24306505
TI  - Incidence and correlates of bulimic behavior in a female high school population.
AB  - To investigate the incidence and correlates of bulimic behavior, 1268 high school
      females were surveyed. A 47-item questionnaire was used to identify a group of
      students that would meet the DSM-III criteria for a probable diagnosis of
      bulimia. Students were then compared across the four content areas of
      demographics; body perception and weight information; dieting, exercise and
      menstrual behavior; and frequency of bingeing and purging behavior. Results
      indicated that 4.9% of the students met rigorous criteria for the diagnosis of
      bulimia. Between-group comparisons indicated that body dissatisfaction, drive for
      thinness, and chronicity of dieting differentiated the two groups. 

PMID- 24306506
TI  - Correlates of romantic attachment: A path analysis study.
AB  - A path-analytic study was undertaken to investigate the proposed relationship
      between physical attractiveness, need for intimacy, self-disclosure, thought
      about one's dating partner, and reported romantic love. Extrapolations from
      theories by Murstein (1971) and I. Reiss (1960), and conclusions from other
      empirical work, provided the background for the assessment of the relationship
      between the four proposed predictive factors and the development of romantic
      affect. During the winter of 1977-78 656 college students responded to a survey
      assessing each of the four predictors and romantic love. Path structures were
      initially estimated for male and female subsamples. Since few significant sex
      differences were noted, coefficients were compared for groups of students
      involved in dating relationships of varying durations. All four predictors were
      significantly associated with the subjects' self-reported romantic affect toward
      their dating partner. In all analyses, thinking about one's partner was found to
      be the most potent predictor. The data suggest the earlier work by Murstein and
      Reiss offer both testable and productive theoretical foundations for the study of
      romantic involvement. However, in future work it would be beneficial to (a)
      search for more numerous and powerful antecedents to romantic love; (b) delineate
      the specific role of cognitive processes in influencing romantic attachment; (c)
      compare relationships on criteria other than months of involvement; and (d) seek
      to examine love from the perspectives of both individuals involved in the dyadic
      relationship. 

PMID- 24306507
TI  - Decade differences in rural adolescents' views of life possibilities.
AB  - In a small-town high school ninth-graders were administered the same research
      instrument in 1967 and 1979. They listed events they thought would happen to them
      in the future, occupations, free-time activities, and people known, and answered
      questions related to perceptions of autonomy and family decision making. Except
      for the time span of future events, which remained between four and five years
      ahead, the later group showed many significant increases in cognitive
      possibilities, especially for occupations and free-time activities. Boys in 1979
      perceived less family cohesiveness and girls more autonomy than their 1967
      counterparts. Content analyses showed expansion of the girls' possibilities into
      formerly male-stereotyped occupations and an increase in perceptions of sexual
      and possibly antisocial activities, particularly among boys. 

PMID- 24306508
TI  - Behavior problems of handicapped adolescent female students.
AB  - Adolescent girls aged 12 through 16 years, identified as either educable mentally
      retarded, behaviorally disordered, learning disabled, or nonhandicapped, were
      rated by their teachers on the Behavior Problem Checklist. Analysis of these
      ratings revealed significant differences for pupil category, Behavior Problem
      Checklist dimension, and category-by-dimension interaction. Behaviorally
      disordered students showed a greater degree of maladjustment than the retarded
      and nonhandicapped students on all four checklist dimensions, and exceeded the
      learning disabled on three dimensions (not Personality Problem). Implications for
      further research and special educational practices based on the present findings
      are discussed. 

PMID- 24306509
TI  - Developmental trends and gender differences in the relation between understanding
      of friendship and asociality.
AB  - The relation between understanding of friendship and asociality was examined in
      91 girls and 104 boys ranging in age from 9 to 17 years. Consistent with previous
      research, older children had higher understanding of friendship scores than
      younger children, and girls had higher understanding of friendship scores than
      boys. The relation between understanding of friendship and asociality was
      significant only for boys. Difficulty in understanding components of friendship
      appears to be one correlate of boys' delinquent tendencies. 

PMID- 24306510
TI  - A social skills analysis in childhood and adolescence using symbolic
      interactionism.
AB  - Support is obtained from the literature about the need for advances in the
      conceptualization of "social skills." There is agreement that much is known about
      how to improve social skills, but less attention has been given to what to change
      or improve. The present article outlines a model of social skills in childhood
      and adolescence using the concepts and literature on symbolic interactionism in
      an attempt to provide a possible conceptual framework for social skills. The
      proposed model is organized around the concepts of role-taking, role-making,
      definition of the situation, and self. Each concept is taken in turn and how it
      could contribute to the analysis or understanding of social skills in childhood
      and adolescence is shown. The article concludes with a discussion of ways in
      which the proposed scheme might be used in one area of social skills - friendship
      making. Some possible difficulties and limitations in the model are noted. 

PMID- 24306511
TI  - Synthesis of thioamides via one-pot A(3)-coupling of alkynyl bromides, amines,
      and sodium sulfide.
AB  - We herein describe a novel method for the synthesis of thioamides by a three
      component condensation of alkynyl bromides, amines, and Na2S.9H2O. The developed
      method is applicable for a wide range of amines and alkynyl bromides bearing
      different functional groups furnishing the corresponding products in moderate to
      excellent yields. 

PMID- 24306512
TI  - Fatty acid synthase inhibitor C75 ameliorates experimental colitis.
AB  - Abnormalities of lipid metabolism through overexpression of fatty acid synthase
      (FASN), which catalyzes the formation of long-chain fatty acids, are associated
      with the development of inflammatory bowel disease (IBD). C75 is a synthetic
      alpha-methylene-gamma-butyrolactone compound that inhibits FASN activity. We
      hypothesized that C75 treatment could effectively reduce the severity of
      experimental colitis. Male C57BL/6 mice were fed 4% dextran sodium sulfate (DSS)
      for 7 d. C75 (5 mg/kg body weight) or dimethyl sulfoxide (DMSO) (vehicle) was
      administered intraperitoneally from d 2 to 6. Clinical parameters were monitored
      daily. Mice were euthanized on d 8 for histological evaluation and measurements
      of colon length, chemokine, cytokine and inflammatory mediator expression. C75
      significantly reduced body weight loss from 23% to 15% on d 8, compared with the
      vehicle group. The fecal bleeding, diarrhea and colon histological damage scores
      in the C75-treated group were significantly lower than scores in the vehicle
      animals. Colon shortening was significantly improved after C75 treatment. C75
      protected colon tissues from DSS-induced apoptosis by inhibiting caspase-3
      activity. Macrophage inflammatory protein 2, keratinocyte-derived chemokine,
      myeloperoxidase activity and proinflammatory cytokines (tumor necrosis factor
      alpha, interleukin [IL]-1beta and IL-6) in the colon were significantly
      downregulated in the C75-treated group, compared with the vehicle group.
      Treatment with C75 in colitis mice inhibited the elevation of FASN,
      cyclooxygenase-2 and inducible nitric oxide synthase expression as well as
      IkappaB degradation in colon tissues. C75 administration alleviates the severity
      of colon damage and inhibits the activation of inflammatory pathways in DSS
      induced colitis. Thus, inhibition of FASN may represent an attractive therapeutic
      potential for treating IBD. 

PMID- 24306513
TI  - Deep brain stimulation for tremor resulting from acquired brain injury.
AB  - OBJECTIVES: To evaluate the efficacy of deep brain stimulation (DBS) in the
      treatment of tremor resulting from acquired brain injury (ABI). METHODS: A series
      of eight consecutive patients with post-ABI tremor were treated with DBS of the
      ventro-oralis posterior (VOP)/zona incerta (ZI) region, and subsequently
      underwent blinded assessments using Bain's tremor severity scale. RESULTS: VOP/ZI
      DBS produced a mean reduction in tremor severity of 80.75% based on Bain's tremor
      severity scale, with significant reductions in all five component tremor
      subscores: rest, postural, kinetic, proximal and distal. No adverse neurological
      complications were reported, although one patient experienced exacerbation of pre
      existing gait ataxia. CONCLUSION: VOP/ZI stimulation is demonstrated here to be
      an effective and safe approach for the treatment of post-ABI tremor in the
      largest series published at the time of writing.

PMID- 24306514
TI  - Initial clinical application of modified Dixon with flexible echo times: hepatic
      and pancreatic fat assessments in comparison with (1)H MRS.
AB  - OBJECTS: Hepatic and pancreatic fat content become increasingly important for
      phenotyping of individuals with metabolic diseases. This study aimed to (1)
      evaluate hepatic fat fractions (HFF) and pancreatic fat fractions (PFF) using
      (1)H magnetic resonance spectroscopy (MRS) and the recently introduced fast
      mDixon method, and to examine body fat effects on HFF and PFF, (2) investigate
      regional differences in HFF and PFF by mDixon. MATERIALS AND METHODS: HFF and PFF
      were quantified by mDixon with two flexible echo times and by single voxel (1)H
      MRS in 24 healthy subjects. The regional differences of PFF within the pancreas
      were assessed with mDixon. Abdominal visceral and subcutaneous fat was assessed
      by T1-weighted MRI at 3T. RESULTS: Both methods correlated well for
      quantification of HFF (r = 0.98, p < 0.0001) and PFF (r = 0.80, p < 0.0001).
      However, mDixon showed a higher low limit in HFF and PFF. PFF showed no regional
      differences using mDixon. In addition, both visceral and subcutaneous fat
      correlated with pancreatic fat, while only visceral fat correlated with liver
      fat, employing both (1)H MRS and mDixon. CONCLUSION: The novel and fast two-point
      mDixon exhibits a good correlation with the gold-standard (1)H MRS for assessment
      of HFF and PFF, with limited sensitivity for assessing lower fat content.

PMID- 24306515
TI  - Attitudes and knowledge of medical practitioners to hereditary cancer clinics and
      cancer genetic testing.
AB  - Genetic testing for susceptibility for common cancers is widely available. Thus,
      doctors have a role in identifying and referring patients who would benefit from
      a consultation with a specialist in genetics. This study aims to assess doctors'
      referral rates, knowledge and attitudes towards cancer genetic testing, broken
      down by specialty (gastrointestinal, breast/ovarian, other specialties and
      General Practitioners-GPs). A 4-page questionnaire was mailed out to the GPs of
      all patients seen in 2012 in the Hereditary Cancer Clinic of St. Vincent's
      Hospital Sydney (n = 128) and all the specialists in St. Vincent's Hospital
      Sydney that might refer to the HCC (n = 33). 50 questionnaires were returned (31
      %). Most doctors had referred a patient for cancer genetic testing (90 %). The
      average proportion of patients referred was 1 in 68.5 patients with
      breast/ovarian specialists referring the most, followed by gastrointestinal
      specialists and GPs. There was suboptimal knowledge of cancer genetic testing
      amongst doctors. Breast/ovarian specialists were most knowledgeable, followed by
      gastrointestinal specialists, other specialists and GPs. There were indications
      of inappropriate referral amongst doctors. Most (77.6 %) doctors were willing to
      receive further information on cancer genetics. Nearly all (94 %) doctors believe
      that it is their duty to inform an individual at high risk for hereditary cancer
      that cancer genetic counselling and testing is available. The majority of doctors
      have positive attitudes towards cancer genetic testing. Defective knowledge
      scores, however, indicate that doctors need further training or tools to enable
      them to refer patients appropriately for cancer genetic testing.

PMID- 24306516
TI  - Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic
      differentiation of rat osteoblasts.
AB  - In the present study, the effects of bone morphogenetic protein-2 (BMP-2),
      vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) on regulation of rat osteoblast (ROB) maturation in vitro were
      investigated. It was found that the proliferation, differentiation and
      mineralization of ROBs were all dose-dependently increased at particular times in
      the case of treatment with only one growth factor. To investigate the effects of
      combined treatment, ROBs were treated with either a single application of a
      relatively high dose of each growth factor, or binary/triple combined
      applications of relatively low doses of the growth factors. Osteogenic
      differentiation was significantly promoted in the triple combination treatment of
      BMP-2, VEGF and bFGF compared with the single or binary combination treatments.
      The optimal timing of the triple combination to enhance osteogenesis was also
      tested. When bFGF and VEGF were added in the early stage, and BMP-2 and VEGF were
      added in the late stage, osteogenic differentiation of ROBs could be enhanced
      more effectively. These results could be used to construct bone tissue
      engineering scaffolds that release growth factors sequentially. 

PMID- 24306517
TI  - Ca(2+) transport in mitochondrial and microsomal fractions from higher plants.
AB  - Mitochondria from etiolated corn possess a much greater Ca(2+) uptake capacity
      per mg protein than microsomes from the same source. Differences in energy
      requirements, sensitivity to specific inhibitors, and sedimentation properties
      enabled us to study both Ca(2+) uptake mechanisms without mutual contamination.
      The microsomal Ca(2+) uptake does not vary much among different plants as
      compared to the mitochondrial Ca(2+) uptake; this is also true for different
      organs of the same plant. Mitochondrial Ca(2+) uptake is more dependent on the
      age of the seedlings than microsomal uptake, because of changes in active Ca(2+)
      uptake activity rather than of changes in efflux. Intactness and the oxidative
      and phosphorylative properties of the mitochondria remained unchanged during this
      time period. Na(+) and Mg(2+) do not induce Ca(2+) release from mitochondria. 

PMID- 24306518
TI  - Auxin-binding by particulate fractions from tobacco leaf protoplasts.
AB  - In vitro binding of 1-naphthaleneacetic acid (NAA) to particulate fractions from
      tobacco leaf protoplasts was studied. In freshly isolated protoplasts no specific
      binding could be detected, whereas it was present in particulate fractions from
      tobacco leaves. It is concluded that the NAA-binding-sites are probably located
      at the external face of the plasma membrane; they are destroyed during protoplast
      isolation by proteolytic enzymes in the cellulase and macerozyme preparations.
      After culturing the protoplasts for 3-4 d, the first cell divisions were observed
      and at the same time specific NAA-binding became detectable. The affinity
      constant for NAA was approx. 2.10(6) mol(-1) and the number of binding sites
      increased during further culture. 

PMID- 24306519
TI  - The roles of nitrate and ammonium in the regulation of the development of nitrate
      reductase in Chlamydomonas reinhardii.
AB  - The regulation of the development of nitrate reductase (NR) activity in
      Chlamydomonas reinhardii has been compared in a wild-type strain and in a mutant
      (nit-A) which possesses a modified nitrate reductase enzyme that is non
      functional in vivo. The modified enzyme cannot use NAD(P)H as an electron donor
      for nitrate reduction and it differs from wild-type enzyme in that NR activity is
      not inactivated in vitro by incubation with NAD(P)H and small quantities of
      cyanide; it is inactivated when reduced benzyl viologen or flavin mononucleotide
      is present. After short periods of nitrogen starvation mutant organisms contain
      much higher levels of terminal-NR activity than do similarly treated wild-type
      ones. Despite the inability of the mutant to utilize nitrate, no nitrate or
      nitrite was found in nitrogen-starved cultures; it is therefore concluded that
      the appearance of NR activity is not a consequence of nitrification. After
      prolonged nitrogen starvation (22 h) the NR level in the mutant is low. It
      increases rapidly if nitrate is then added and this increase in activity does not
      occur in the presence of ammonium, tungstate or cycloheximide. Disappearance of
      preformed NR activity is stimulated by addition of tungstate and even more by
      addition of ammonium. The results are interpreted as evidence for a continuous
      turnover of NR in cells of the mutant with ammonium both stimulating NR breakdown
      and stopping NR synthesis. Nitrate protects the enzyme from breakdown. Reversible
      inactivation of NR activity is thought to play an insignificant role in the
      mutant. 

PMID- 24306520
TI  - Nucleic acid and protein synthesis and loss of vigour in germinating wheat
      embryos.
AB  - A study has been made of the RNA and protein synthesising systems of wheat
      embryos isolated from seed lots having high viability but differing in vigour.
      The rate of RNA and protein synthesis in wheat embryos during the early hours of
      germination is related to the vigour of the seed lot. The imposition of a stress
      factor, in the nature of a sub-optimal germination temperature, during
      germination of isolated wheat embryos magnifies the differences in rates of
      protein and RNA synthesis between high and low vigour seed. Using cell-free
      protein synthesising systems it has been demonstrated that an important
      difference between high and low vigour embryos lies in the relative levels of
      messenger RNA in the embryo. High vigour embryos contain relatively higher levels
      of poly A(+)-RNA (i.e. potential mRNA species) than lower vigour embryos and
      furthermore the level of poly A(+)-RNA in high vigour embryos increases during
      early germination whilst in lower vigour embryos the level decreases. The
      difference in poly A(+)-RNA levels accounts, at least partially, for the
      differences in rates of protein synthesis observed between embryos from high and
      low vigour wheat seed during early germination at both optimal and sub-optimal
      germination temperatures. 

PMID- 24306521
TI  - Hydroxyurea-induced mitotic synchronization in Allium sativum root meristems.
AB  - The synchronized divisions following a treatment with hydroxyurea (HU) - an
      inhibitor of DNA synthesis - were studied in root meristems of Allium sativum
      using two methods: autoradiography of median sections and morphological labeling
      with a cytokinesis inhibitor. It is shown that the second wave of mitoses is
      heterogeneous: it is composed mostly of cells which have been synchronized in the
      S phase by the HU treatment, of cells coming from the quiescent center stimulated
      to enter DNA synthesis and of cells which were not blocked by the 23 h HU
      treatment (slow cycling cells). It is also shown that the cell cycle following
      the first synchronized division is considerably shortened by the synchronization
      procedure. 

PMID- 24306522
TI  - Effect of indoleacetic acid, abscisic acid, root tips and coleoptile tips on
      growth and curvature of maize roots.
AB  - The effect of externally applied indoleacetic acid (IAA) and abscisic acid (ABA)
      on the growth of roots of Zea mays L. was measured. Donor blocks of agar with IAA
      or ABA were placed laterally on the roots and root curvature was measured. When
      IAA was applied to vertical roots, a curvature directed toward the donor block
      was observed. This curvature corresponded to a growth inhibition at the side of
      the root where the donor was applied. When IAA was applied to horizontal roots
      from the upper side, normal geotropic downward bending was delayed or totally
      inhibited. The extent of retardation and the inhibition of curvature were found
      to depend on the concentration of IAA in the donor block. ABA neither induced
      curvature in vertical roots nor inhibited geotropic curvature in horizontal
      roots; thus the growth of roots was not inhibited by ABA. However, when, instead
      of donor blocks, root tips or coleoptile tips were placed onto vertical roots, a
      curvature of the roots was observed. 

PMID- 24306523
TI  - Geotropic curvature of decapitated Avena coleoptiles after application of tips of
      maize roots, tips of Avena coleoptiles, indoleacetic acid, or abscisic acid.
AB  - Isolated Avena coleoptiles were decapitated at different distances from the tip
      and then placed horizontally, after which the geotropic curvature was measured.
      No geotropic curvature could be detected during the first 3 h. Later, upward
      curvature occurred which was found to depend inversely on the length of the
      decapitated tips. When the tips of maize roots or Avena coleoptiles were placed
      on the cut surface of decapitated Avena coleoptiles, the coleoptiles showed a
      significantly stronger upward curvature as compared to controls which had been
      provided with agar blocks on the cut surface. The same upward curvature was found
      with decapitated coleoptiles provided with agar blocks containing 10(-6) or 10(
      7) M indoleacetic acid (IAA). After application of abscisic acid (ABA) at
      concentrations of 10(-6) and 10(-8) M to the decapitated coleoptiles, the
      curvature observed was not different from that of the controls; at higher
      concentrations of ABA the curvature was found to be lower than that of the
      controls. It is concluded that root tips secrete a substance which may replace
      the effect of IAA in coleoptiles. The results are discussed in view of the
      validity of the Cholodny-Went hypothesis for the geotropic reaction of roots. 

PMID- 24306524
TI  - Differential expression of the genes for ribulose-1,5-bisphosphate carboxylase
      and light-harvesting chlorophyll a/b protein in the developing barley leaf.
AB  - The expression of genes in particular for light-harvesting chlorophyll a/b
      protein (LHCP) and ribulose-1,5-bisphosphate carboxylase (RuBPCase) has been
      studied in the developing barley leaf. This has been done by analysis of the
      occurrence of both proteins within the different regions (1 to 6, beginning from
      the base) of the primary 7-day-old leaf. It has been found that LHCP already
      appears in the base of the leaf, whereas RuBPCase is primarily expressed in the
      apical expanding part of the leaf. The distribution of the mRNAs for both
      proteins within this gradient is in accordance with that of the proteins
      themselves, indicating that gene expression is not regulated at the level of
      translation in both cases. The poly(A) mRNA for LHCP occurs mainly in the basic
      sections 2 and 3, whereas that for RuBPCase is found throughout the leaf but
      primarily in the apical sections of the leaf. 

PMID- 24306525
TI  - Metabolism of [(13)C 1]gibberellin A 29 to [ (13)C 1]gibberellin-catabolite in
      maturing seeds of Pisum sativum cv. Progress No. 9.
AB  - The metabolism of GA29 during seed maturation in Pisum sativum cv. Progress No. 9
      was further investigated. [17-(13)C1]GA29 was metabolised to a GA-catabolite
      (structure 3), with incorporation of the [(13)C] label from the GA29 substrate
      into the GA-catabolite being demonstrated by GC-MS. Quantitation of the GA
      catabolite using GC-MS was achieved by adding GA-catabolite, labelled with
      [(18)O], to seed extracts as an internal standard. At least 50% conversion of
      [(13)C1]GA29 to [(13)C1]GA-catabolite was demonstrated with the build up of
      exogenous [(13)C1]GA-catabolite strictly paralleling the accumulation of native
      GA-catabolite. These results strongly suggest that conversion of GA29 to the GA
      catabolite is a natural metabolic step occurring during the final stages of seed
      maturation. 25 MUg per seed of native GA-catabolite was recorded in 37 day old
      seeds. Some problems encountered in the analysis of extracts containing the GA
      catabolite are discussed briefly. 

PMID- 24306526
TI  - Lag-phase and rate of synthesis in phytochrome-mediated induction of
      phenylalanine ammonia-lyase in mustard (Sinapis alba L.) cotyledons.
AB  - Mustard seedlings were irradiated with continuous far-red light either with or
      without far-red preirradiation for between 6 and 44 h. The preirradiation
      increases the rate of light-mediated phenylalanine ammonia-lyase (EC 4.3.1.5)
      accumulation in the cotyledons up to 5-fold but does not eliminate the apparent
      lag-phase of induction which lasts between 30 and 60 min, both with and without a
      preirradiation. No differential effect of inhibitors presumed to be acting close
      to gene transcription was observed for plants, whether given a preirradiation or
      not. These results do not support the notion that two different induction
      mechanisms are involved in the action of phytochrome on phenylalanine ammonia
      lyase synthesis during primary and secondary irradiation. There was however a
      strong promotive effect of preirradiation on P fr-mediated enzyme accumulation
      which can be explained by an elevated level of the rate of enzyme synthesis left
      over from the previous light treatment and a transient increase in the capacity
      of the system to increase the rate of enzyme synthesis in response to active
      phytochrome. 

PMID- 24306527
TI  - The isolation of endoplasmic reticulum from barley aleurone layers.
AB  - Techniques for the isolation and purification of endoplasmic reticulum (ER) from
      aleurone layers of barley (Hordeum vulgare L.) were assessed. Neither
      differential centrifugation nor density gradient centrifugation of a homogenate
      separate the ER or other organelles of this tissue from the lipidcontaining
      spherosomes. Isopycnic sucrose gradient centrifugation of organelles first
      purified by molecular sieve chromatography on Sepharose 4B, however, results in
      separation of the organelles based on their differing buoyant densities.
      Manipulation of the magnesium concentration of the isolation media and density
      gradient solutions affords isolation of ER at a density of 1.13-1.14 g cc(-1) and
      1.17-1.18 g cc(-1). Electron microscopy shows that the membranes sedimenting at
      1.13-1.14 g cc(-1) are devoid of ribosomes and are characteristic of smooth ER,
      while those sedimenting at 1.17-1.18 g cc(-1) are studded with ribosomes and have
      the features of rough ER. Endoplasmic reticulum isolated by isopycnic density
      gradient centrifugation can be further purified by rate-zonal centrifugation. 

PMID- 24306528
TI  - Quantitative and qualitative changes in the endoplasmic reticulum of barley
      aleurone layers.
AB  - Changes in the level of the endoplasmicreticulum (ER) marker enzyme cytochrome-c
      reductase (EC 1.6.2.1) were followed with time of imbibition of de-embryonated
      half-seeds of barley (Hordeum vulgare L.) and the subsequent incubation of their
      aleurone layers in gibberellic acid (GA3) and H2O. During imbibition there is an
      increase in the level of cytochrome-c-reductase activity and in the amount of 280
      nm absorbance associated with this enzyme. When aleurone layers are incubated for
      a further 42 h in water, there is a doubling of the cytochrome-c-reductase
      activity. In GA3, the activity of cytochrome-c reductase reaches a maximum at 24
      h of incubation and thereafter falls to below 70% of its level at the beginning
      of the incubation period. Changes in the cytochrome-c-reductase activity
      correlate with changes in the fine structure of the aleurone cell. The ER
      isolated in low Mg(2+) from aleurone layers incubated in buffer for up to 18 h
      has buoyant density of 1.13-1.14 g cc(-1) while that from layers incubated in GA3
      for 7.5-18 h has a density of 1.11-1.12 g cc(-1). The alpha-amylase (EC3.2.1.1)
      isolated with the organelle fraction by Sepharose gel filtration is associated
      with the ER on isopycnic and rate-zonal density gradients, and its activity can
      be enhanced by Triton X-100. The soluble alpha-amylase fraction from Separose-4B
      columns, on the other hand, is not Triton-activated but is acid-labile. Acid
      phosphatase (EC3.1.3.2) is distributed in at least three peaks on isopycnic
      gradients. In low Mg(2+) the second peak of activity has a density of 1.12 g cc(
      1) in GA3-treated tissue and 1.13-1.14 g cc(-1) in H2O-treated tissue. With high
      Mg(2+) buffers, this peak of phosphatase activity disappears. Acid-phosphatase
      activity is not enhanced by Triton X-100 nor is it acid-labile. 

PMID- 24306529
TI  - What is pea legumin - Is it glycosylated?
AB  - Since there is some question as to whether or not legumin is glycosylated, this
      storage protein was isolated by various procedures from developing cotyledons of
      Pisum sativum L. supplied with [(14)C]-labeled glucosamine and analyzed by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis. Legumin isolated by the
      classical method of Danielsson [(1949) Biochem. J. 44, 387-400] a procedure in
      which globulins extracted with a buffered salt solution are precipitated with
      ammonium sulfate (70% saturation) and legumin separated from vicilin by
      isoelectric precipitation, was labeled. The glucosamine incorporated into legumin
      was associated with low-molecular-weight polypeptides. In contrast, legumin
      isolated by the method of Casey [(1979) Biochem. J. 177, 509-520], a procedure
      where legumin is prepared by zonal isoelectric precipitation from globulins
      precipitated with 40-70% ammonium sulfate, was not labeled. However, the globulin
      fraction precipitated with 40% ammonium sulfate was labeled and the radioactive
      glucosamine was associated with low-molecular-weight polypeptides. Legumin
      isolated from protein bodies [Thomson et al. (1978) Aust. J. Plant Physiol. 5,
      263-279] was not extensively labeled. However, the saltinsoluble fraction of
      protein body extracts was labeled and the radioactivity was associated with low
      molecular-weight polypeptides. These results indicate that protein bodies contain
      a glycoprotein of low-molecular-weight that co-purifies with legumin isolated by
      the method of Danielsson but that is discarded when isolation methods developed
      more recently are used. 

PMID- 24306530
TI  - Patterns of polypeptide synthesis in various maize organs under anaerobiosis.
AB  - The pattern of protein synthesis was compared in several organs of maize (Zea
      mays L.) under aerobic and anaerobic conditions. Protein synthesis was measured
      by [(35)S]methionine incorporation and analysis by two-dimensional native-SDS
      (sodium lauryl sulfate) polyacrylamide gel electrophoresis and fluorography. The
      aerobic protein-synthesis profiles were very different for root, endosperm,
      scutellum and anther wall. However, except for some characteristic qualitative
      and quantitative differences, the patterns of protein synthesis during
      anaerobiosis were remarkably similar for these diverse organs and also for
      mesocotyl and coleoptile. The proteins synthesized were the anaerobic
      polypeptides (ANPs) which have been previously described in anaerobic roots of
      seedlings. Leaves exhibited no detectable protein synthesis under anaerobic
      conditions, and died after a short anaerobic treatment. Evidence is presented
      that the ANPs are not a generalized response to stress. This indicates that the
      ANPs are synthesized as a specific response to anaerobic conditions such as
      flooding. 

PMID- 24306531
TI  - Photoresponsive polymer nanocarriers with multifunctional cargo.
AB  - Nanoparticles with photoresponsive character can be assembled from amphiphilic
      macromolecular components and hydrophobic chromophores. In aqueous solutions, the
      hydrophobic domains of these species associate to produce spontaneously nanosized
      hosts with multiple photoresponsive guests in their interior. The modularity of
      this supramolecular approach to nanostructured assemblies permits the co
      encapsulation of distinct subsets of guests within the very same host. In turn,
      the entrapped guests can be designed to interact upon light excitation and
      exchange electrons, energy or protons. Such photoinduced processes permit the
      engineering of properties into these supramolecular constructs that would
      otherwise be impossible to replicate with the separate components. Alternatively,
      noninteracting guests with distinct functions can be entrapped in these
      supramolecular containers to ensure multifunctional character. In fact,
      biocompatible luminescent probes with unique photochemical and photophysical
      signatures have already emerged from these fascinating investigations. Thus,
      polymer nanocarriers can become invaluable supramolecular scaffolds for the
      realization of multifunctional and photoresponsive tools for a diversity of
      biomedical applications. 

PMID- 24306532
TI  - Leaf shrinkage with dehydration: coordination with hydraulic vulnerability and
      drought tolerance.
AB  - Leaf shrinkage with dehydration has attracted attention for over 100 years,
      especially as it becomes visibly extreme during drought. However, little has been
      known of its correlation with physiology. Computer simulations of the leaf
      hydraulic system showed that a reduction of hydraulic conductance of the
      mesophyll pathways outside the xylem would cause a strong decline of leaf
      hydraulic conductance (K(leaf)). For 14 diverse species, we tested the hypothesis
      that shrinkage during dehydration (i.e. in whole leaf, cell and airspace
      thickness, and leaf area) is associated with reduction in K(leaf) at declining
      leaf water potential (Psi(leaf)). We tested hypotheses for the linkage of leaf
      shrinkage with structural and physiological water relations parameters, including
      modulus of elasticity, osmotic pressure at full turgor, turgor loss point (TLP),
      and cuticular conductance. Species originating from moist habitats showed
      substantial shrinkage during dehydration before reaching TLP, in contrast with
      species originating from dry habitats. Across species, the decline of K(leaf)
      with mild dehydration (i.e. the initial slope of the K(leaf) versus Psi(leaf)
      curve) correlated with the decline of leaf thickness (the slope of the leaf
      thickness versus Psi(leaf) curve), as expected based on predictions from computer
      simulations. Leaf thickness shrinkage before TLP correlated across species with
      lower modulus of elasticity and with less negative osmotic pressure at full
      turgor, as did leaf area shrinkage between full turgor and oven desiccation.
      These findings point to a role for leaf shrinkage in hydraulic decline during
      mild dehydration, with potential impacts on drought adaptation for cells and
      leaves, influencing plant ecological distributions.

PMID- 24306533
TI  - Plantation forestry under global warming: hybrid poplars with improved
      thermotolerance provide new insights on the in vivo function of small heat shock
      protein chaperones.
AB  - Climate-driven heat stress is a key factor affecting forest plantation yields.
      While its effects are expected to worsen during this century, breeding more
      tolerant genotypes has proven elusive. We report here a substantial and durable
      increase in the thermotolerance of hybrid poplar (Populus tremula*Populus alba)
      through overexpression of a major small heat shock protein (sHSP) with convenient
      features. Experimental evidence was obtained linking protective effects in the
      transgenic events with the unique chaperone activity of sHSPs. In addition,
      significant positive correlations were observed between phenotype strength and
      heterologous sHSP accumulation. The remarkable baseline levels of transgene
      product (up to 1.8% of total leaf protein) have not been reported in analogous
      studies with herbaceous species. As judged by protein analyses, such an
      accumulation is not matched either by endogenous sHSPs in both heat-stressed
      poplar plants and field-grown adult trees. Quantitative real time-polymerase
      chain reaction analyses supported these observations and allowed us to identify
      the poplar members most responsive to heat stress. Interestingly, sHSP
      overaccumulation was not associated with pleiotropic effects that might decrease
      yields. The poplar lines developed here also outperformed controls under in vitro
      and ex vitro culture conditions (callus biomass, shoot production, and ex vitro
      survival), even in the absence of thermal stress. These results reinforce the
      feasibility of improving valuable genotypes for plantation forestry, a field
      where in vitro recalcitrance, long breeding cycles, and other practical factors
      constrain conventional genetic approaches. They also provide new insights into
      the biological functions of the least understood family of heat shock protein
      chaperones.

PMID- 24306534
TI  - MAKER-P: a tool kit for the rapid creation, management, and quality control of
      plant genome annotations.
AB  - We have optimized and extended the widely used annotation engine MAKER in order
      to better support plant genome annotation efforts. New features include better
      parallelization for large repeat-rich plant genomes, noncoding RNA annotation
      capabilities, and support for pseudogene identification. We have benchmarked the
      resulting software tool kit, MAKER-P, using the Arabidopsis (Arabidopsis
      thaliana) and maize (Zea mays) genomes. Here, we demonstrate the ability of the
      MAKER-P tool kit to automatically update, extend, and revise the Arabidopsis
      annotations in light of newly available data and to annotate pseudogenes and
      noncoding RNAs absent from The Arabidopsis Informatics Resource 10 build. Our
      results demonstrate that MAKER-P can be used to manage and improve the
      annotations of even Arabidopsis, perhaps the best-annotated plant genome. We have
      also installed and benchmarked MAKER-P on the Texas Advanced Computing Center. We
      show that this public resource can de novo annotate the entire Arabidopsis and
      maize genomes in less than 3 h and produce annotations of comparable quality to
      those of the current The Arabidopsis Information Resource 10 and maize V2
      annotation builds. 

PMID- 24306535
TI  - The effect of right terminal repeat deletion on the oncogenicity of the T-Region
      of pTiT37.
AB  - A modified pTiT37 plasmid was constructed by deleting a 103 base fragment between
      an AhaIII and a Bc/I site. This fragment, located to the right of the nopaline
      synthase gene contains the right terminal 25 base pair repeat sequence which
      defines the right limit of the T-Region. The effect of this deletion was
      determined on a number of host plants. In contrast to previous reports, the
      deletion does not destroy tumorigenicity on all plant species. It had no effect
      on tumorigenicity when Linum usitatissimum was used as the test species and an
      attenuating effect when Kalanchoe tubiflora was used. Only when Nicotiana tabacum
      was used did the mutant appear avirulent. We propose from these data and the
      phenotype of those tumours that form, that a pseudo border located in the 3'
      untranslated region of the ipt locus has been used to provide the right hand
      limit of the T-Region in the absence of the normal border. 

PMID- 24306536
TI  - alpha-amylase genes of wheat are two multigene families which are differentially
      expressed.
AB  - The alpha-Amy1 and alpha-Amy2 genes of wheat produce distinct subsets of alpha
      amylase isozymes which show different patterns of expression in wheat aleurone
      cells and in developing grain. In order to characterise the organisation and
      expression of these genes, clones of alpha-Amy1 and alpha-Amy2 cDNA have been
      isolated. The two types of cDNA clone were distinguished within a small library
      of alpha-amylase cDNA clones (Baulcombe and Buffard, Planta 157 493-501 [1983])
      by restriction endonuclease mapping and by cross hybridisation. The identity of
      alpha-Amy1 or alpha-Amy2 type was assigned from the results of hybrid selected
      translation analysis in which small subfragments of the cDNA clones were used.
      These subfragments were derived from the 3' ends of the cDNA and did not cross
      hybridise between the different types of cDNA. Hybridisation of alpha-Amy1 and
      alpha-Amy2 cDNA probes to restriction enzyme digests of wheat nuclear DNA
      revealed that these are multigene families located on the group 6 (alpha-Amy1)
      and group 7 (alpha-Amy2) chromosomes. Studies on the levels of alpha-Amy1 and
      alpha-Amy2 mRNA in developing grain and in aleurone tissue indicated that the
      differences in isozyme expression are due to the patterns of mRNA accumulation.
      In aleurone tissue the alpha-Amy1 transcripts accumulate in parallel with other
      genes which are regulated by gibberellic acid, while the accumulation of alpha
      Amy2 genes is sustained for 36 h longer. 

PMID- 24306537
TI  - Partial characterisation of different classes of viral DNA, and kinetics of DNA
      synthesis in turnip protoplasts infected with cauliflower mosaic virus.
AB  - Turnip protoplasts infected with cauliflower mosaic virus (CaMV) have been used
      to examine the kinetics of CaMV DNA synthesis, and the different classes of CaMV
      DNA found in vivo partially characterised. Differential extraction techniques for
      DNA from infected protoplasts has identified several distinct classes of viral
      DNA. The same approach applied to virus preparations revealed that while the
      majority of virion DNA was stably encapsidated, some small DNAs and a
      heterogeneous population 3.8-ca. 5.0 Kb were not. The structural relationship of
      sa-DNA (3) with the particle is such that only its 5' RNA moeity is susceptible
      to nuclease attack. Two-dimensional gel electrophoresis of total CaMV DNA from
      infected protoplasts revealed all the DNA species found in virion DNA, those
      species representing the 'free' DNA class and a further class of molecules, rich
      in DNA of (-) polarity (24), to which the role of reverse transcription
      intermediates has been ascribed. 'Free' DNA contains 8 Kb supercoiled DNA (Form I
      DNA), an 8 Kb open circle (Form II), an 8 Kb linear (Form III) and a truncated
      molecule with an extension of the (-) strand previously observed from infected
      plants (10). Kinetic experiments show that the accumulation of total CaMV-DNA
      parallels the accumulation of progeny virions to reach a maximum around 72 h post
      inoculation and that there is not a separation of CaMV-DNA synthesis into clearly
      defined early and late stages. 

PMID- 24306538
TI  - Nucleotide sequences and stability of a Nicotiana nuclear DNA segment possessing
      autonomously replicating ability in yeast.
AB  - The nucleotide sequence of a tobacco (Nicotiana tabacum) chromosomal DNA
      segment(t3-ars) capable of replication in yeast (ars: autonomously replicating
      sequences) is presented. The subcloned region (618 bp) contained 11 bp consensus
      (5' A/TTTTATPuTTTA/T 3') essential for several yeast ars, and 73% A and T. Unique
      70 bp repetitive sequences resided next to this sequence. Thirty-two bp AT
      repeats were also seen in the neighbourhood of the repetitive sequence. The
      hybrid plasmid containing t3-ars was mitotically stabilized by the help of yeast
      centromere (CEN4). 

PMID- 24306539
TI  - Sequence analysis of Vicia faba highly repeated DNA: the BamHI repeated sequence
      families.
AB  - Cleavage of Vicia faba nuclear DNA with the restriction endonuclease BamHI
      yielded discrete size classes of 250, 850, 900, 990, 1 150, 1 500 and 1 750 bp of
      highly repetitive DNA. Each of these sequence families comprised about 3% of the
      total genomic DNA. Some sequence members from each sequence family were cloned in
      pBR322 and their primary structures determined. Computer analyses of nucleotide
      sequences suggested the existence of about 60 bp sequence periodicity within the
      repeating unit of the 990 bp sequence family, though the extent of homology among
      the surmised shorter subrepeat units was very low. With other BamHI sequence
      families, however, the data did not show any clear internal sequence periodicity.
      The repeat units of the 850 bp and 1 750 bp sequence families contained
      nucleotide sequences homologous to the 250 bp family sequence. No sequence
      relationship between or among other sequence families was observed. There was 13
      25% sequence variation among 6 cloned members of the 250 bp family and probably
      also among those of other BamHI repeat families. DNA sequences homologous to
      these V. faba BamHI repeat families were detected in Pisum sativum DNA by
      Southern blot hybridization. Furthermore, very weak cross-hybridization was
      observed with plant DNAs from Phaseolus vulgaris, Triticum aestivum, Cucumis
      sativus and Trillium kamtschaticum. 

PMID- 24306540
TI  - Cellular double-stranded RNA in Phaseolus vulgaris.
AB  - High molecular weight double-stranded (ds) RNAs have been detected in apparently
      virus-free French (common) bean Phaseolus vulgaris cv. Black Turtle Soup (BTS).
      Several other bean cultivars were free of detectable high molecular weight
      dsRNAs. The dsRNAs have been partially characterized and have homology to the BTS
      genome as well as to the genomes of other bean cultivars. The T m of hybrids
      formed between BTS DNA and denatured dsRNA have been estimated. 

PMID- 24306541
TI  - Assessment of detached podocytes in the Bowman's space as a marker of disease
      activity in lupus nephritis.
AB  - Podocyte damage is an important pathogenic component of glomerular disease
      progression. This study is a trial to clarify the value of counting and scoring
      the number of shed Bowman's space podocytes as an activity parameter of lupus
      nephritis, a trial that has not been conducted before. This study was performed
      on 42 female patients with the clinical diagnosis of lupus nephritis. Beside the
      routine stains tissue sections were stained by colloidal iron and anti
      podocalyxin for sialomucin. Podocytes in the Bowman's space were counted and
      scored. Thorough statistical work was carried out to correlate the podocyte
      scores with the morphological lesions of lupus nephritis. This study revealed
      significant association and correlation of shed Bowman's space podocytes with
      histopathological parameters of activity in different classes of lupus nephritis.
      We concluded that counting and scoring shed Bowman's space podocytes is
      statistically significant as a marker of disease activity in lupus nephritis. It
      can be one of the parameters of activity index but not of chronicity index. 

PMID- 24306542
TI  - Association of muscle strength, power, and optimal shortening velocity with
      functional abilities of women with chronic osteoarthritis participating in a
      multi-modal exercise program.
AB  - We assessed the relative association of quadriceps muscle strength and power as
      well as optimal shortening velocity (upsilon(opt)) to physical functioning in 28
      women aged 50-87 years with chronic osteoarthritis participating in a three-week
      multimodal exercise program. Quadriceps muscle strength, power, upsilon(opt), and
      functional performance using the Activities of Daily Living (ADL) scale, Timed Up
      & Go (TUG) test, Tinetti test, and 6-Minute Walking Test (6-MWT) were assessed
      pre- and postrehabilitation. With rehabilitation, patients improved the values of
      strength, power, and the results of all functional tests. Both at baseline and
      postrehabilitation, functional status was more strongly related to power and
      upsilon(opt) than to strength. Functional gains obtained with rehabilitation were
      not related to changes in power or upsilon(opt), and only very modestly related
      to changes in strength. Future studies should assess the benefits and feasibility
      of power- and velocity-oriented training in patients with osteoarthritis.

PMID- 24306543
TI  - Ti(3+)-defected and V-doped TiO2 quantum dots loaded on MCM-41.
AB  - V-doped TiO2 quantum dots (QDs) possessing many Ti(3+) defects were fabricated by
      simple hydrolysis using MCM-41 as a support. The QDs show high charge-separation
      efficiency and high photocatalytic activity due to the quantum size effect and
      the newly formed defect- and dopant-mediated band levels. 

PMID- 24306544
TI  - Ultrastructure of exocrine prothoracic gland ofDatana ministra (Drury)
      (Lepidoptera: Notodontidae) and the nature of its secretion.
AB  - Datana ministra larvae possess a gland situated in the ventral anterior portion
      of the prothorax. The gland consists of a single sac and is only charged with
      secretion in the last instar. Its orifice, a simple slit, opens into a transverse
      invagination of the integument in the cervical margin of the prosternite. The
      components of the gland have been identified by GC and GCMS and have been shown
      to be dodecanol, dodecyl acetate, and dodecyl formate. The morphology of the
      gland and the chemistry of the secretion are discussed in relation to other
      notodontid larvae which have been investigated. It is conjectured that the
      secretion is not defensive in nature but may function as a dispersal pheromone. 

PMID- 24306545
TI  - Identification of the sex attractant pheromone of the southwestern corn
      borerDiatraea grandiosella Dyar.
AB  - We report the identification of the southwestern corn borer,Diatraea grandiosella
      Dyar (Lepidoptera: Pyralidae), female sex attractant pheromone as a mixture of
      (Z)-9-hexadecenal, (Z)-11-hexadecenal, and (Z)-13-octadecenal in the ratio
      21.5?70.6?7.9. Initially, six 16- and 18-carbon aldehydes includingn-hexadecanal,
      (Z)-9-octadecenal, (Z)-11-octadecenal, and the three above were isolated from
      female gland rinses and evaluated as potential pheromone components by GLC-MS and
      laboratory bioassays. By laboratory flight chamber and field tests, the stated
      mixture of (Z)-9-hexadecenal, (Z)-11-hexadecenal, and (Z)-13-octadecenal was
      shown to be as effective as the female for male attraction. Electrophysiological
      studies confirmed the requirement for these three compounds, but not forn
      hexadecanal, (Z)-9-octadecenal, and (Z)-11-octadecenal. 

PMID- 24306546
TI  - Sex-identifying urine and molt signals in lobster (Homarus americanus).
AB  - During courtship, premolt female lobsters,Homarus americanus, choose a male and
      initiate a pair bond by repeated approaches to his shelter. The male allows such
      a female to share his shelter for about one week. This knowledge formed the basis
      to search for quantitative evidence for lobster sex pheromone(s) used in
      courtship: male cues to allow premolt females to identify a preferred male, and
      female cues to allow males to identify a premolt mature female. In each of four
      1500-liter naturalistic aquaria, the behavioral responses of one female and two
      male lobsters to male and female lobster urine (0.5 ml) and body odor (20 ml)
      stimuli were observed. These stimuli were injected once or twice per day into a
      continuously flowing delivery tube attached to lobster shelters. Habituation to
      stimulus introduction-a serious problem in earlier experiments-was apparently
      avoided in the more natural social and physical environment we employed in these
      experiments. We demonstrated that male and female molt body odors contain
      different chemical substances: females responded to male molt body odor and males
      responded to female molt body odor but not vice versa. In general, male and
      female intermolt urine caused strong responses; however, females responded only
      weakly to male urine. This suggests that male and female urine are chemically
      different. Female urine and molt body odor caused a typically male "high-on-legs"
      response. These results show that molt body odors and intermolt urine contain sex
      specific substances, which may be used in lobster courtship as well as other
      social interactions. 

PMID- 24306547
TI  - Correlation of retention times on liquid crystal capillary column with reported
      vapor pressures and half-lives of compounds used in pheromone formulations.
AB  - A method has been developed to determine by capillary gas chromatography on
      liquid crystal stationary phases the relative vapor pressures and half-lives of
      many compounds used as insect pheromones. This study demonstrated that the
      retention time of seven acetates on a liquid crystal column (cholesteryl-p
      chlorocinnamate) could be correlated closely to the reported vapor pressures of
      the compounds. For 13 additional pheromonal acetates and alcohols, reported half
      lives showed a high degree of correlation with their retention times on the
      liquid crystal column. Thus chromatography on capillary liquid crystal gas
      Chromatographie columns appears to be a useful method for determining the
      relative volatilities of many pheromones to facilitate the development of more
      precise formulations. 

PMID- 24306548
TI  - Persistence of nonprotein seed amino acid s-(beta-carboxyethyl)-cysteine in young
      leaves ofCalliandra rubescens Ecological implications.
AB  - The insecticidal nonprotein amino acid S-(beta-carboxyethyl)-cysteine (S-CEC) is
      the major free amino acid in the seeds of severalCalliandra spp. where it
      accounts for up to 2.9 % of dry weight. Lesser amounts of other related S
      containing amino acids and an array of nonprotein imino acids derived from
      pipecolic acid are other constituents. High concentrations of imino acids, which
      also show insecticidal activity, are maintained in the mature leaves, but sulfur
      compounds are lacking. In this study the disappearance of S-CEC from the
      germinating seeds and young seedlings ofC. rubescens was monitored over time.
      After 10 weeks, S-CEC continues to be found in high concentrations in the stems
      and new leaves. As young leaves mature, sulfur compounds quickly decrease in
      concentration. Traces of S-CEC are found in new leaves of plants up to nine
      months after germination. Whether high concentration of S-CEC in young leaves is
      due to transportation from the seed or de novo synthesis is unclear. The
      ecological implications are discussed. 

PMID- 24306550
TI  - Poultry slaughtering practices in rural communities of Bangladesh and risk of
      avian influenza transmission: a qualitative study.
AB  - Slaughtering sick poultry is a risk factor for human infection with highly
      pathogenic avian influenza and is a common practice in Bangladesh. This paper
      describes human exposures to poultry during slaughtering process and the customs
      and rituals influencing these practices in two Bangladeshi rural communities. In
      2009, we conducted 30 observations to observe slaughtering practices and 110 in
      depth and short interviews and 36 group discussions to explore reasons behind
      those practices. The villagers reported slaughtering 103 poultry, including 20
      sick poultry during 2 months. During different stages of slaughtering, humans,
      the environment, healthy poultry, and other animals were exposed to poultry blood
      and body parts. Women performed most of the slaughtering tasks, including
      evisceration. Defeathering required the most time and involved several persons.
      During festivals, ceremonies, and rituals, many people gathered and participated
      in the slaughtering of poultry. Exposure to poultry slaughtering created numerous
      opportunities for potential avian influenza transmission. Strategies that can be
      further tested to determine if they reduce the risk of transmission include
      skinning the carcasses of sick poultry, using hot water for defeathering and
      cleaning, using a bucket to contain slaughtering blood and carcass, burying the
      offal and encouraging handwashing. 

PMID- 24306551
TI  - Aquatic macroinvertebrate assemblages of Ghana, West Africa: understanding the
      ecology of a neglected tropical disease.
AB  - Buruli ulcer (BU) is an emerging, but neglected tropical disease, where there has
      been a reported association with disturbed aquatic habitats and proposed aquatic
      macroinvertebrate vectors such as biting Hemiptera. An initial step in
      understanding the potential role of macroinvertebrates in the ecology of BU is to
      better understand the entire community, not just one or two taxa, in relation to
      the pathogen, Mycobacterium ulcerans, at a large spatial scale. For the first
      time at a country-wide scale this research documents that M. ulcerans was
      frequently detected from environmental samples taken from BU endemic regions, but
      was not present in 30 waterbodies of a non-endemic region. There were significant
      differences in macroinvertebrate community structure and identified potential
      indicator taxa in relation to pathogen presence. These results suggest that
      specific macroinvertebrate taxa or functional metrics may potentially be used as
      aquatic biological indicators of M. ulcerans. Developing ecological indicators of
      this pathogen is a first step for understanding the disease ecology of BU and
      should assist future studies of transmission. 

PMID- 24306552
TI  - Attempted detection of Toxoplasma gondii oocysts in environmental waters using a
      simple approach to evaluate the potential for waterborne transmission in the
      Galapagos Islands, Ecuador.
AB  - Toxoplasmosis is a health concern for wildlife and humans, particularly in island
      ecosystems. In the Galapagos Islands, exposure to Toxoplasma gondii has been
      found in marine avifauna on islands with and without domestic cats. To evaluate
      potential waterborne transmission of T. gondii, we attempted to use filtration
      and epifluorescent microscopy to detect autofluorescent T. gondii oocysts in
      fresh and estuarine surface water samples. T. gondii oocyst-like structures were
      microscopically visualized but were not confirmed by polymerase chain reaction
      and sequence analyses. Further research is needed to refine environmental
      pathogen screening techniques and to evaluate disease risk of waterborne zoonoses
      such as T. gondii for wildlife and humans, particularly in the Galapagos and
      other naive island ecosystems. 

PMID- 24306553
TI  - Clinical significance of post-interventional cerebral hyperdensities after
      endovascular mechanical thrombectomy in acute ischaemic stroke.
AB  - INTRODUCTION: This study aims to investigate the clinical significance of post
      interventional cerebral hyperdensities (PCHD) after endovascular mechanical
      thrombectomy in acute ischaemic stroke. METHODS: Data of 102 consecutive patients
      who received post-interventional CT scans within 4.5 h after mechanical
      thrombectomy were analysed retrospectively. RESULTS: Sixty-two of 102 patients
      (60.8 %) had PCHD on their post-interventional CT scans. The most common site of
      PCHD was the basal ganglia. PCHD were persisting in 13 of 62 patients (21.0 %),
      and transient in the remaining 49 patients (79.0 %) within 24 h. Four patients
      with PCHD and four patients without PCHD suffered from parenchymal haemorrhage.
      Neither ASA nor Clopidogrel, Tirofiban or rtPA were risk factors for PCHD. Final
      infarction size was congruent with or bigger than areas of PCHD in 93.3 % of
      cases in our series. CONCLUSION: PCHD was not a risk factor for parenchymal
      haemorrhage in our series. The occurrence of PCHD was strongly related to the
      prior presence of infarction. PCHD was also a strong predictor for final
      infarction size.

PMID- 24306555
TI  - Consistent Partial Least Squares for nonlinear structural equation models.
AB  - Partial Least Squares as applied to models with latent variables, measured
      indirectly by indicators, is well-known to be inconsistent. The linear compounds
      of indicators that PLS substitutes for the latent variables do not obey the
      equations that the latter satisfy. We propose simple, non-iterative corrections
      leading to consistent and asymptotically normal (CAN)-estimators for the loadings
      and for the correlations between the latent variables. Moreover, we show how to
      obtain CAN-estimators for the parameters of structural recursive systems of
      equations, containing linear and interaction terms, without the need to specify a
      particular joint distribution. If quadratic and higher order terms are included,
      the approach will produce CAN-estimators as well when predictor variables and
      error terms are jointly normal. We compare the adjusted PLS, denoted by PLSc,
      with Latent Moderated Structural Equations (LMS), using Monte Carlo studies and
      an empirical application. 

PMID- 24306554
TI  - Phenotype gene expression differences between resistant and susceptible salmon
      families to IPNV.
AB  - Infectious pancreatic necrosis virus (IPNV) is an economically important pathogen
      of the salmonid aquaculture industry. Selective breeding has been employed to
      improve resistance to this infectious disease, and it is of importance to
      investigate the expression profile of immune genes of Atlantic salmon with
      different genetic background in response to this virus. This study examined the
      immune modulation response of eight candidate genes in head kidney tissue in two
      families of Atlantic salmon with high and low mortalities, after challenge with
      IPNV. The results showed that the expression pattern of target genes differed in
      the two families. Generally, higher expression of antiviral, pro-inflammatory
      genes and transcription factors such as tripartite motif, NF-kappaB, IFNI, STAT1,
      protein kinase R, and Vig-2 in the resistant family were observed at the same
      time point. One may speculate the functional importance of these putative
      candidate genes in the characterization of the IPNV-resistant (low mortalities)
      immune phenotype. Therefore, on our findings, we suggest that future salmonids
      studies aiming to identify candidate genes/pathway or vaccines evaluation should
      consider validating detected genes/pathway across different genetic backgrounds
      or immune phenotype. 

PMID- 24306556
TI  - Comment on the asymptotics of a distribution-free goodness of fit test statistic.
AB  - In a recent article Jennrich and Satorra (Psychometrika 78: 545-552, 2013) showed
      that a proof by Browne (British Journal of Mathematical and Statistical
      Psychology 37: 62-83, 1984) of the asymptotic distribution of a goodness of fit
      test statistic is incomplete because it fails to prove that the orthogonal
      component function employed is continuous. Jennrich and Satorra (Psychometrika
      78: 545-552, 2013) showed how Browne's proof can be completed satisfactorily but
      this required the development of an extensive and mathematically sophisticated
      framework for continuous orthogonal component functions. This short note provides
      a simple proof of the asymptotic distribution of Browne's (British Journal of
      Mathematical and Statistical Psychology 37: 62-83, 1984) test statistic by using
      an equivalent form of the statistic that does not involve orthogonal component
      functions and consequently avoids all complicating issues associated with them. 

PMID- 24306557
TI  - Quantile lower bounds to reliability based on locally optimal splits.
AB  - Extending the theory of lower bounds to reliability based on splits given by
      Guttman (in Psychometrika 53, 63-70, 1945), this paper introduces quantile lower
      bound coefficients lambda 4(Q) that refer to cumulative proportions of potential
      locally optimal "split-half" coefficients that are below a particular point Q in
      the distribution of split-halves based on different partitions of variables into
      two sets. Interesting quantile values are Q=0.05,0.50,0.95,1.00 with lambda
      4(0.05)<=lambda 4(0.50)<=lambda 4(0.95)<=lambda 4(1.0). Only the global optimum
      lambda 4(1.0), Guttman's maximal lambda 4, has previously been considered to be
      interesting, but in small samples it substantially overestimates population
      reliability rho. The three coefficients lambda 4(0.05), lambda 4(0.50), and
      lambda 4(0.95) provide new lower bounds to reliability. The smallest, lambda
      4(0.05), provides the most protection against capitalizing on chance
      associations, and thus overestimation, lambda 4(0.50) is the median of these
      coefficients, while lambda 4(0.95) tends to overestimate reliability, but also
      exhibits less bias than previous estimators. Computational theory, algorithm, and
      publicly available code based in R are provided to compute these coefficients.
      Simulation studies evaluate the performance of these coefficients and compare
      them to coefficient alpha and the greatest lower bound under several population
      reliability structures.

PMID- 24306558
TI  - Energy-dependent changes in the ATP/ADP ratio at the tight nucleotide binding
      site of chloroplast ATP synthase.
AB  - Using DTT-modulated thylakoid membranes we studied tight nucleotide binding and
      ATP content in bound nucleotides and in the reaction mixture during [(14)C] ADP
      photophosphorylation. The increasing light intensity caused an increase in the
      rate of [(14)C] ADP incorporation and a decrease in the steady-state level of
      tightly bound nucleotides. Within the light intensity range from 11 to 710 w m(
      2), ATP content in bound nucleotides was larger than that in nucleotides of the
      reaction mixture; the most prominent difference was observed at low degrees of
      ADP phosphorylation. The increasing light intensity was accompanied by a
      significant increase of the relative ATP content in tightly bound nucleotides.
      The ratio between substrates and products formed at the tight nucleotide binding
      site during photophosphorylation was suggested to depend on the light-induced
      proton gradient across the thylakoid membrane. 

PMID- 24306559
TI  - Changes in the cyanobacterial photosynthetic apparatus during acclimation to
      macronutrient deprivation.
AB  - When the cyanobacterium Synechococcus sp. Strain PCC 7942 is deprived of an
      essential macronutrient such as nitrogen, sulfur or phosphorus, cellular
      phycobiliprotein and chlorophyll contents decline. The level of beta-carotene
      declines proportionately to chlorophyll, but the level of zeaxanthin increases
      relative to chlorophyll. In nitrogen- or sulfur-deprived cells there is a net
      degradation of phycobiliproteins. Otherwise, the declines in cellular
      pigmentation are due largely to the diluting effect of continued cell division
      after new pigment synthesis ceases and not to net pigment degradation. There was
      also a rapid decrease in O2 evolution when Synechococcus sp. Strain PCC 7942 was
      deprived of macronutrients. The rate of O2 evolution declined by more than 90% in
      nitrogen- or sulfur-deprived cells, and by approximately 40% in phosphorus
      deprived cells. In addition, in all three cases the fluorescence emissions from
      Photosystem II and its antennae were reduced relative to that of Photosystem I
      and the remaining phycobilisomes. Furthermore, state transitions were not
      observed in cells deprived of sulfur or nitrogen and were greatly reduced in
      cells deprived of phosphorus. Photoacoustic measurements of the energy storage
      capacity of photosynthesis also showed that Photosystem II activity declined in
      nutrient-deprived cells. In contrast, energy storage by Photosystem I was
      unaffected, suggesting that Photosystem I-driven cyclic electron flow persisted
      in nutrient-deprived cells. These results indicate that in the modified
      photosynthetic apparatus of nutrient-deprived cells, a much larger fraction of
      the photosynthetic activity is driven by Photosystem I than in nutrient-replete
      cells. 

PMID- 24306560
TI  - Structure-function studies on the interaction of PsaC with the Photosystem 1
      heterodimer : The site directed change R561E in PsaB destabilizes the subunit
      interaction in Synechocystis sp. PCC 6803.
AB  - The interaction of PsaC with the core heterodimer of Photosystem 1 was studied in
      wild type Synechocystis sp. PCC 6803 and the site-directed mutant R561E of PsaB.
      The mutant reaction center was much less stable in urea and the functional
      reconstitution of the mutant core using PsaC was impaired. However, the extent of
      reconstitution increased in the presence of divalent cations whereas that of the
      wild type was inhibited. We conclude that the reaction center in the mutant is
      unstable, most likely due to the introduction of an unfavorable electrostatic
      interaction between surface-exposed residues on PsaC and the binding site for the
      subunit on the core heterodimer in support of the model proposed previously
      (Rodday et al. (1993) Photosynth Res 36: 1-9). 

PMID- 24306561
TI  - Analysis of xanthophyll cycle carotenoids and chlorophyll fluorescence in light
      intensity-dependent chlorophyll-deficient mutants of wheat and barley.
AB  - Three light intensity-dependent Chl b-deficient mutants, two in wheat and one in
      barley, were analyzed for their xanthophyll cycle carotenoids and Chl
      fluorescence characteristics under two different growth PFDs (30 versus 600 MUmol
      photons.m(-2) s(-1) incident light). Mutants grown under low light possessed
      lower levels of total Chls and carotenoids per unit leaf area compared to wild
      type plants, but the relative proportions of the two did not vary markedly
      between strains. In contrast, mutants grown under high light had much lower
      levels of Chl, leading to markedly greater carotenoid to Chl ratios in the
      mutants when compared to wild type. Under low light conditions the carotenoids of
      the xanthophyll cycle comprised approximately 15% of the total carotenoids in all
      strains; under high light the xanthophyll cycle pool increased to over 30% of the
      total carotenoids in wild type plants and to over 50% of the total carotenoids in
      the three mutant strains. Whereas the xanthophyll cycle remained fairly
      epoxidized in all plants grown under low light, plants grown under high light
      exhibited a considerable degree of conversion of the xanthophyll cycle into
      antheraxanthin and zeaxanthin during the diurnal cycle, with almost complete
      conversion (over 90%) occurring only in the mutants. 50 to 95% of the xanthophyll
      cycle was retained as antheraxanthin and zeaxanthin overnight in these mutants
      which also exhibited sustained depressions in PS II photochemical efficiency
      (Fv/Fm), which may have resulted from a sustained high level of photoprotective
      energy dissipation activity. The relatively larger xanthophyll cycle pool in the
      Chl b-deficient mutant could result in part from the reported concentration of
      the xanthophyll cycle in the inner antenna complexes, given that the Chl b
      deficient mutants are deficient in the peripheral LHC-II complexes. 

PMID- 24306562
TI  - Comparative study of reaction centers from purple photosynthetic bacteria:
      Isolation and optical spectroscopy.
AB  - Reaction centers from two species of purple bacteria, Rhodospirillum rubrum and
      Rhodospirillum centenum, have been characterized and compared to reaction centers
      from Rhodobacter sphaeroides and Rhodobacter capsulatus. The reaction centers
      purified from these four species can be divided into two classes according to the
      spectral characteristics of the primary donor. Reaction centers from one class
      have a donor optical band at a longer wavelength, 865 nm compared to 850 nm, and
      an optical absorption band associated with the oxidized donor at 1250 nm that has
      a larger oscillator strength than reaction centers from the second class. Under
      normal buffering conditions, reaction centers isolated from Rb. sphaeroides and
      Rs. rubrum exhibit characteristics of the first class while those from Rb.
      capsulatus and Rs. centenum exhibit characteristics of the second class. However,
      the reaction centers can be converted between the two groups by the addition of
      charged detergents. Thus, the observed spectral differences are not due to
      intrinsic differences between reaction centers but represent changes in the
      electronic structure of the donor due to interactions with the detergents as has
      been confirmed by recent ENDOR measurements (Rautter J, Lendzian F, Lubitz W,
      Wang S and Allen JP (1994) Biochemistry 33: 12077-12084). The oxidation midpoint
      potential for the donor has values of 445 mV, 475 mV, 480 mV and 495 mV for Rs.
      rubrum, Rs. centenum, Rb. capsulatus, and Rb. sphaeroides, respectively. Despite
      this range of values for the midpoint potential, the decay rates of the
      stimulated emission are all fast with values of 4.1 ps, 4.5 ps. 5.5 ps and 6.1 ps
      for quinone-reduced RCs from Rs. rubrum, Rb. capsulatus, Rs. centenum, and Rb.
      sphaeroides, respectively. The general spectral features of the initial charge
      separated state are essentially the same for the four species, except for
      differences in the wavelengths of the absorption changes due to the different
      donor band positions. The pH dependence of the charge recombination rates from
      the primary and secondary quinones differ for reaction centers from the four
      species indicating different interactions between the quinones and ionizable
      residues. A different mechanism for charge recombination from the secondary
      quinone, that probably is direct recombination, is proposed for RCs from Rs.
      centenum. 

PMID- 24306563
TI  - Changes in the photosynthetic light response curve during leaf development of
      field grown maize with implications for modelling canopy photosynthesis.
AB  - Changes in the photosynthetic light-response curve during leaf development were
      determined for the fourth leaf of maize crops sown on 23 April and 10 June.
      Temperatures were unusually mild during late spring/early summer and neither crop
      experienced chilling damage. The concept of thermal time was used to take into
      account the effects of different temperature regimes on developmental stage,
      thereby enabling photosynthetic light-response data to be combined for both crops
      to describe the general response. Large variations in the upper asymptote (Asat)
      and convexity (Theta) of the light-response curve occurred during leaf
      development, but the maximum quantum yield of CO2 assimilation remained
      relatively constant throughout. Dark respiration rates showed a small but
      significant decrease with leaf age and generally ranged between 5 and 10% of
      Asat. A simple mathematical model was developed to assess the sensitivity of
      daily leaf photosynthesis (AL) to reductions in the Asat, Theta and the initial
      slope (Phi) of the light-response curve at different stages of leaf development.
      On bright sunny days, and at all developmental stages, AL was ca. twice as
      sensitive to reductions in Asat than to reductions in Phi and Theta. In overcast
      conditions, however, all three parameters contributed significantly to reductions
      in leaf photosynthesis, although the contribution of Phi was greatest during
      early leaf growth, while older leaves were most sensitive to depressions in Asat.
      The implications of these results for modelling the sensitivity of canopy
      photosynthesis to chill-induced photoinhibition of the light-response curve are
      discussed. 

PMID- 24306564
TI  - Inactivation of the water-oxidizing enzyme in manganese stabilizing protein-free
      mutant cells of the cyanobacteria Synechococcus PCC7942 and Synechocystic PCC6803
      during dark incubation and conditions leading to photoactivation.
AB  - The previously constructed MSP (manganese stabilizing protein-psbO gene product)
      free mutant of Synechococcus PCC7942 (Bockholt R, Masepohl B and Pistorius E K
      (1991) FEBS Lett 294: 59-63) and a newly constructed MSP-free mutant of
      Synechocystis PCC6803 were investigated with respect to the inactivation of the
      water-oxidizing enzyme during dark incubation. O2 evolution in the MSP-free
      mutant cells, when measured with a sequence of short saturating light flashes,
      was practically zero after an extended dark adaptation, while O2 evolution in the
      corresponding wild type cells remained nearly constant. It could be shown that
      this inactivation could be reversed by photoactivation. With isolated thylakoid
      membranes from the MSP-free mutant of PCC7942, it could be demonstrated that
      photoactivation required illumination in the presence of Mn(2+) and Ca(2+), while
      Cl(-) addition was not required under our experimental conditions. Moreover, an
      extended analysis of the kinetic properties of the water-oxidizing enzyme
      (kinetics of the S3->(S4)->S0 transition, S-state distribution, deactivation
      kinetics) in wild type and mutant cells of Synechococcus PCC7942 and
      Synechocystis PCC6803 was performed, and the events possibly leading to the
      reversible inactivation of the water-oxidizing enzyme in the mutant cells are
      discussed. We could also show that the water-oxidizing enzyme in the MSP-free
      mutant cells is more sensitive to inhibition by added NH4Cl-suggesting that NH3
      might be a physiological inhibitor of the water oxidizing enzyme in the absence
      of MSP. 

PMID- 24306565
TI  - Extraction of DNA from milligram amounts of fresh, herbarium and mummified plant
      tissues.
AB  - We have developed a DNA extraction procedure for milligram amounts of plant
      tissue. Yields ranged from 0.3-200 nanograms of DNA per milligram of tissue. The
      factors affecting yield are discussed. Fresh tissue, as well as herbarium
      specimens (22-118 years old) and mummified seeds and embryos (500 to greater than
      44 600 years old) were used. All tissues attempted (57 types from 29 species)
      yielded measurable amounts of DNA. In no case tested was inhibition observed for
      restriction enzymes BamHI or EcoRI. 

PMID- 24306566
TI  - A 21 kilobase-pair deletion/addition difference in the inverted repeat sequence
      of chloroplast DNA from Chlamydomonas eugametos and C. moewusii.
AB  - Our recent physical mapping of chloroplast DNA (cpDNA) from Chlamydomonas
      moewusii, a unicellular green alga which is interfertile with Chlamydomonas
      eugametos, has revealed a two-fold size difference between the inverted repeat
      sequences of these algae. With a size of 42 kbp, the inverted repeat of C.
      moewusii is the largest yet identified in any chloroplast genome. Here we have
      compared the arrangement of conserved sequences within the two algal inverted
      repeats by hybridizing cloned restriction fragments representing over 90% of
      these repeats to Southern blots of cpDNA digests from the two algae. We found
      that the size difference between the two algal inverted repeats is due to the
      presence of an extra DNA segment of 21 kilobase pairs (kbp) in C. moewusii.
      Except for this sequence, the C. moewusii inverted repeat is highly homologous to
      the entire C. eugametos repeat and the arrangement of conserved sequences in the
      two repeats is identical. Southern hybridizations with specific gene probes
      revealed that the conserved sequences include the rDNA region and the genes
      coding for the large subunit of ribulose 1,5 bisphosphate carboxylase-oxygenase
      (rbcL) and for the '32 kilodalton' thylakoid membrane protein (psbA). With
      respect to the conserved sequences, the extra 21 kbp DNA segment of C. moewusii
      lies in the region of psbA, most probably slightly downstream from this gene. 

PMID- 24306567
TI  - Non-oncogenic plant vectors for use in the agrobacterium binary system.
AB  - Agrobacterium strains harbouring the T-region and the virulence-region of the Ti
      plasmid on separate replicons still display efficient T-DNA transfer to plants.
      Based on this binary vector strategy we have constructed T-region derived gene
      vectors for the introduction of foreign DNA into plants. The vectors constructed
      can replicate in E. coli, thus the genetic manipulations with them can be
      performed with E. coli as a host. They can be transferred to Agrobacterium as a
      cointegrate with the wide host range plasmid R772. Their T-regions are
      transferred to plant cells from Agrobacterium strains conferring virulence
      functions.The plasmid pRAL 3940 reported here is 11.5 kb large, contains a marker
      to identify transformed plant cells and unique restriction sites for direct
      cloning of passenger DNA, flanked by the left- and right-hand border fragments of
      the T-region (including the 25 bp border repeats). The plasmid is free of onc
      genes. Therefore, is does not confer tumorigenic traits on the transformed plant
      cells and mature, fertile plants can thus be regenerated from them. 

PMID- 24306568
TI  - Phytochrome regulation of phytochrome mRNA abundance.
AB  - Pure phytochrome RNA sequence synthesized in an SP6-derived in vitro
      transcription system has been used as a standard to quantitate phytochrome mRNA
      abundance in Avena seedlings using a filter hybridization assay. In 4-day-old
      etiolated Avena seedlings phytochrome mRNA represents ~0.1% of the total
      poly(A)(+) RNA. Irradiation of such seedlings with a saturating red-light pulse
      or continuous white light induces a decline in this mRNA that is detectable
      within 30 min and results in a 50% reduction by ~60 min and >90% reduction within
      5 h. The effect of the red-light pulse is reversed, approximately to the level of
      the far-red control, by an immediately subsequent far-red pulse. In seedlings
      maintained in extended darkness after the red-light pulse, the initial rapid
      decline in phytochrome mRNA level is followed by a slower reaccumulation such
      that 50-60% of the initial abundance is reached by 48 h. White-light grown
      seedlings transferred to darkness exhibit a similar accumulation of phytochrome
      mRNA that is accelerated by removal of residual Pfr with a far-red light pulse at
      the start of the dark period. The data establish that previously reported
      phytochrome-regulated changes in translatable phytochrome mRNA levels result from
      changes in the physical abundance of this mRNA rather than from altered
      translatability. 

PMID- 24306569
TI  - Resistance to hygromycin B : A new marker for plant transformation studies.
AB  - A bacterial gene encoding hygromycin phosphotransferase has been modified for
      expression in tobacco cells. The aphIV gene from Escherichia coli was inserted
      between the 5' sequence of an octopine synthase gene and the 3' sequence from a
      nopaline synthase gene. The new gene was incorporated between T-DNA border
      fragments in the broad-host-range vector pKT210 to form a micro-Ti plasmid.
      Agrobacterium tumefaciens containing this plasmid and a Ti plasmid as helper was
      used to incite crown gall tumors on aseptic tobacco plants. Samples of these
      galls could grow in the presence of hygromycin B, provided that the aph gene had
      been fused with the ocs gene to maintain the sense of the coding sequences. When
      the genes had been fused in the reverse 'antisense' orientation none of the gall
      samples could grow on hygromycin. Unlike wild-type galls the hygromycin-resistant
      tissue contained DNA sequences homologous to the aphIV gene. Thus the modified
      gene can be introduced into tobacco cells and confer on them the ability to grow
      in the presence of hygromycin B. 

PMID- 24306570
TI  - Restriction fragment polymorphisms as probes for plant diversity and their
      development as tools for applied plant breeding.
AB  - Maize and tomato cDNA clones have been hybridized in Southern blotting
      experiments to plant genomic DNA prepared from different lines to detect
      restriction fragment polymorphisms (RFPs). In maize we have found that a high
      degree of genetic variability is present, even among domestic inbred lines. Most
      randomly chosen maize cDNA clones can be used to detect elements of this
      variability. Similar levels of polymorphism are observed when genomic DNA is
      digested with any of a number of different restriction enzymes and probed with
      individual clones. When a clone is hybridized to genomic DNAs prepared from
      several different maize lines, a number of different alleles are often detected
      at a single locus. At the same time one clone can often detect more than one
      independently segregating locus by cross hybridization to related sequences at
      other loci. As expected these markers are inherited as simple codominant
      Mendelian alleles from one generation to the next and colinkage of these markers
      can be demonstrated in the progeny from a heterozygous parent. In similar studies
      with tomato, remarkably different results were found. Few RFPs were demonstrable
      among domestic Lycopersicon esculentum lines although a higher level of
      variability could be detected when comparing esculentum with its wild
      Lycopersicon relatives. These results are discussed in relation to the applied
      uses of RFPs in plant breeding as well as the inherent variability of different
      plant genomes. 

PMID- 24306571
TI  - Nucleotide sequence of the soybean mitochondrial 18S rRNA gene: evidence for a
      slow rate of divergence in the plant mitochondrial genome.
AB  - The nucleotide sequence of the 18S rRNA gene from soybean mitochondria was
      determined and is presented here in comparison to the 18S rRNA genes from wheat
      and maize mitochondria. All three genes exhibit remarkable sequence similarity
      supporting the proposal that there is a slower rate of nucleotide divergence in
      plant mitochondrial DNA (mtDNA) as compared to the mtDNA of animals. A lower
      degree of sequence similarity is observed between the dicotyledenous plant
      soybean and either wheat (84%) or maize (85%) than between the two monocots
      (96%). A possible secondary structure for the soybean 18S rRNA is presented that
      is analogous to the proposed structure for the E. coli 16S rRNA. 

PMID- 24306572
TI  - Computer analysis identifies sequence homologies between potential gene products
      of Maize Streak Virus and those of Cassava Latent Virus and Tomato Golden Mosaic
      Virus.
AB  - The amino acid sequences of the putative polypeptides of maize streak virus (MSV)
      have been systematically compared with those of cassava latent virus (CLV) and
      tomato golden mosaic virus (TGMV) using the programme DIAGON (8).Conserved
      sequences have been detected between peptides encoded by the complementary (-)
      sense of MSV and those of CLV and TGMV, viz; the 40 200 Mr polypeptide of CLV-1
      (3) and the 40 285 Mr polypeptide of TGMV-A (4) show extensive homologies with
      the 17 768 Mr and 31 388 Mr polypeptides of MSV (6).Distant and variable
      homologies have been detected between the putative coat protein of MSV when
      compared with those of CLV and TGMV. No other relationships between the potential
      gene products of MSV and those of CLV and TGMV have been detected.The extensive
      homologies detected between the complementary sense encoded peptides suggest that
      they are derived from functional genes, and that the directly conserved sequences
      may contain amino acids essential to the function of these proteins. The less
      extensive homologies among the putative coat proteins are considered in relation
      to their possible structures and functions. 

PMID- 24306573
TI  - A self-image questionnaire for young adolescents (SIQYA): Reliability and
      validity studies.
AB  - This article describes a questionnaire measure of self-image designed for young
      adolescents. It represents a downward extension of the Offer Self-Image
      Questionnaire and utilizes nine scales from that instrument: Emotional Tone,
      Impulse Control, Body Image, Peer Relationships, Family Relationships, Mastery
      and Coping, Vocational/Educational Goals, Psychopathology, and Superior
      Adjustment. This 98-item questionnaire elicits responses on a 6-point Likert-type
      scale. The alpha coefficients for each scale are high, indicating a high degree
      of internal consistency among the items. The validity of this instrument is
      examined through factor analyses and through the association of these scales with
      other measures of self-image. The results suggest that this questionnaire
      provides a useful way to assess self-image among young adolescents. 

PMID- 24306574
TI  - Parental criticism and the adolescent experience.
AB  - In a questionnaire study of 883 high school students, subjects were asked the
      extent to which their parents criticized them for 18 criticizable behaviors or
      attitudes. Over 50% of the respondents reported being criticized for being
      disobedient, lazy, and messy-issues central to family life. Further analyses
      indicated a relationship between perceived criticism and self-image. The more
      criticism the teenager perceived for a specific behavior or attitude (e.g., being
      selfish), the more likely that teenager was to perceive himself/herself as being
      that way. The differential impact of criticism in the context of parental
      rejection was also explored. 

PMID- 24306575
TI  - Defendant characteristics and judgment behaviors of adolescent mock jurors.
AB  - Fictitious court cases involving child abuse were presented to 140 male
      undergraduates and 140 male junior high school students to determine if the
      tendency to deal harshly with alleged criminals is dependent upon certain
      defendant characteristics. Results indicate that younger adolescent jurors give
      longer sentences than older adolescent jurors, and male defendants receive longer
      sentences than female defendants. While no significant main effects for case
      content were found, younger jurors gave longer sentences and attributed more
      responsibility to a parent who beat his/her child, while older adolescent jurors
      attributed more responsibility and prescribed longer sentences to a parent who
      burned the child. Implications for future research with adolescent jurors are
      discussed. 

PMID- 24306576
TI  - Chinese adolescents' self-concept as measured by the offer self-image
      questionnaire.
AB  - This article reports results of a study of self-image among 426 adolescents from
      the Republic of China (Taiwan). Self-image was studied through use of a Chinese
      translation of the Offer Self-Image Questionnaire. Subjects were from public
      schools and a factory setting in the Republic of China. Implications for
      understanding Chinese youth as well as problems in doing cross-cultural research
      are discussed. 

PMID- 24306577
TI  - Interethnic contacts in an alternative educational environment: The Israeli
      Shelef project.
AB  - The purpose of the study was to examine the unique interethnic contact situation
      provided by the Israeli Shelef project and its consequences in changes of ethnic
      stereotypes among Shelef participants. The study population consisted of all 49
      Shelef members during the academic year 1979-1980, who resided in seven different
      development towns. They responded to an anonymous questionnaire which solicited
      information concerning their personal background and measures of interethnic
      relations. The data indicate that the tendency to generalize and to relate to
      people categorically decreased over the year and was replaced by a more
      individualistic approach to people different than one's own. Also, Shelef
      members' valuation of eastern Jews and development townspeople became higher, and
      their readiness to associate with them became complete and unconditional at all
      levels of intimacy. The implications of the project for providing adolescents
      with meaningful experiences, bringing the school and the "real world" closer
      together, are also discussed. 

PMID- 24306578
TI  - Self-disclosure: Implications for the study of parent-adolescent interaction.
AB  - Self-disclosure is a process by which persons make themselves known to each
      other. As such, it is an integral part of the family interaction process. In
      families in which adolescents are present, interaction may change as a result of
      changes in degree, topic, or rate of self-disclosure. Self-disclosure of
      adolescents and parents may change as a result of adolescent development,
      specifically changes in cognitive and physical development and self-concept.
      Implications of changes in self-disclosure are discussed in relation to parent
      adolescent interaction. 

PMID- 24306579
TI  - Primary frozen shoulder: brief review of pathology and imaging abnormalities.
AB  - BACKGROUND: Primary frozen shoulder (FS) is a painful contracture of the
      glenohumeral joint that arises spontaneously without an obvious preceding event.
      Investigation of the intra-articular and periarticular pathology would contribute
      to the treatment of primary FS. REVIEW OF LITERATURE: Many studies indicate that
      the main pathology is an inflammatory contracture of the shoulder joint capsule.
      This is associated with an increased amount of collagen, fibrotic growth factors
      such as transforming growth factor-beta, and inflammatory cytokines such as tumor
      necrosis factor-alpha and interleukins. Immune system cells such as B
      lymphocytes, T-lymphocytes and macrophages are also noted. Active fibroblastic
      proliferation similar to that of Dupuytren's contracture is documented. Presence
      of inflammation in the FS synovium is supported by the synovial enhancement with
      dynamic magnetic resonance study in the clinical setting. CONCLUSION: Primary FS
      shows fibrosis of the joint capsule, associated with preceding synovitis. The
      initiator of synovitis, however, still remains unclear. Future studies should be
      directed to give light to the pathogenesis of inflammation to better treat or
      prevent primary FS.

PMID- 24306580
TI  - Prevalence of neuropathic pain in cases with chronic pain related to spinal
      disorders.
AB  - BACKGROUND: The incidence and characteristics of neuropathic pain associated with
      spinal disorders have not yet been fully clarified. The purpose of this study was
      to investigate the prevalence of neuropathic pain and the degree of deterioration
      of quality of life (QOL) in patients with chronic pain associated with spinal
      disorders who visited orthopedic outpatient clinics. METHODS: This cross
      sectional study was conducted in 1,857 patients recruited from 137 medical
      institutions nationwide. Participants were men and women aged 20-79 years with a
      history of spine-related pain for at least 3 months and a visual analog scale
      (VAS) score of at least 30 in the previous week. Patients were screened using a
      neuropathic pain screening questionnaire. The degree of QOL deterioration and its
      correlation with the presence of neuropathic pain were assessed using the Short
      Form Health Survey with 36 questions (SF-36). RESULTS: Overall prevalence of
      neuropathic pain was 53.3%. It was relatively high in patients with cervical
      spondylotic myelopathy (77.3%) and ligament ossification (75.7%) and relatively
      low in those with low back pain (29.4%) and spondylolysis (40.4%). Only 56.9% of
      patients with radiculopathy were diagnosed with neuropathic pain. Logistic
      regression analysis identified several risk factors, including advanced age,
      severe pain, disease duration of at least 6 months, and cervical lesions. In QOL
      assessment, physical functioning, role-physical, role-emotional, and social
      functioning were severely affected, and this trend was more pronounced in
      patients who were more likely to have neuropathic pain. CONCLUSIONS: The
      frequency of neuropathic pain tended to be higher in patients with diseases
      associated with spinal cord damage and lower in patients with diseases that
      primarily manifested as somatic pain. A bias toward allodynia symptoms in the
      screening questionnaire may have resulted in the failure to diagnose neuropathic
      pain in some patients with radiculopathy. Poor QOL, primarily from the aspect of
      physical functioning, was demonstrated in patients with neuropathic pain
      associated with spinal disorders.

PMID- 24306581
TI  - A multicenter study of ICU telemedicine reengineering of adult critical care.
AB  - BACKGROUND: Few studies have evaluated both the overall effect of ICU
      telemedicine programs and the effect of individual components of the intervention
      on clinical outcomes. METHODS: The effects of nonrandomized ICU telemedicine
      interventions on crude and adjusted mortality and length of stay (LOS) were
      measured. Additionally, individual intervention components related to process and
      setting of care were evaluated for their association with mortality and LOS.
      RESULTS: Overall, 118,990 adult patients (11,558 control subjects, 107,432
      intervention group patients) from 56 ICUs in 32 hospitals from 19 US health-care
      systems were included. After statistical adjustment, hospital (hazard ratio
      [HR]=0.84; 95% CI, 0.78-0.89; P<.001) and ICU (HR=0.74; 95% CI, 0.68-0.79;
      P<.001) mortality in the ICU telemedicine intervention group was significantly
      better than that of control subjects. Moreover, adjusted hospital LOS was
      reduced, on average, by 0.5 (95% CI, 0.4-0.5), 1.0 (95% CI, 0.7-1.3), and 3.6
      (95% CI, 2.3-4.8) days, and adjusted ICU LOS was reduced by 1.1 (95% CI, 0.8
      1.4), 2.5 (95% CI, 1.6-3.4), and 4.5 (95% CI, 1.5-7.2) days among those who
      stayed in the ICU for >=7, >=14, and >=30 days, respectively. Individual
      components of the interventions that were associated with lower mortality,
      reduced LOS, or both included (1) intensivist case review within 1 h of
      admission, (2) timely use of performance data, (3) adherence to ICU best
      practices, and (4) quicker alert response times. CONCLUSIONS: ICU telemedicine
      interventions, specifically interventions that increase early intensivist case
      involvement, improve adherence to ICU best practices, reduce response times to
      alarms, and encourage the use of performance data, were associated with lower
      mortality and LOS.

PMID- 24306582
TI  - Rapid photomodulation of stem extension in light-grownSinapis alba L. : Studies
      on kinetics, site of perception and photoreceptor.
AB  - Treatment of the whole of aSinapis alba plant with supplementary far-red light
      (FR), in back-ground white light (WL), induces a rapid increase in stem extension
      rate. This rapid increase is regulated by the light environment of the stem
      itself. Supplementary FR to the stem increases extension rate after a lag period
      of 10-15 min. A lag period of 3-4 h follows FR irradiation of the leaf, before an
      increase in extension rate is detectable. When the stem is given supplementary
      FR, the change in extension rate which is induced increases with increasing FR
      fluence rate, and with decreasing phytochrome photoequilibrium. There is no
      difference between the effects of supplementary FR lambdamax 719 nm and
      supplementary FR lambdamax 739 nm for these relationships. The increase in
      extension rate induced by supplementary FR is reversed by an increase in the
      fluence rate of red light (R). These data indicate that the response is
      controlled by phytochrome photoequilibrium. 

PMID- 24306583
TI  - Phase transitions in plant cuticles.
AB  - The effect of temperature on wet plant cuticles has been investigated with the
      following techniques: Calorimetry, densitometry, spin-label electron-spin
      resonance-(ESR)-spectroscopy, photo bleaching, and light and electron microscopy.
      At low temperatures cuticles ofCitrus aurantium L. andHedera helix show, at 16.3
      degrees C, a sharp transition (DeltaT~0.5 degrees C) with a latent heat of 4.7+/
      0.5 J g(-1)-cuticle. Below transition: The main orientation of the polymer matrix
      is parallel to the normal of the cuticle and the main orientation of the layer
      with soluble lipids is perpendicular to the normal. The cuticle is in a rigid
      state. Above transition (between 16.3 degrees C and 38 degrees C): Only the
      orientation of the polymer matrix has changed (tilted in parts). There exist
      several very sharp (DeltaT?0.1 degrees C) transitions (38 degrees C, 41 degrees
      C, 45 degrees C, 49 degrees C, ...) with a latent heat in the order of 0.4 J g(
      1)-cuticle. Above 38 degrees C: The lamella of the soluble lipids is in a fluid
      state. Above 45 degrees C there is a change in the molecular orientation of the
      soluble lipids as well as in the polymer matrix. The soluble lipids are mainly
      oriented parallel to the normal. The dry cuticles show no phase transition
      between 0 degrees C and 200 degrees C. At room temperature a dry/wet transition
      can be observed. 

PMID- 24306584
TI  - Unusual fatty acids in the lipids from organs and cell cultures ofPetroselinum
      crispum.
AB  - The lipids of seeds, leaves, and roots of parsley,Petroselinum crispum, and of
      heterotrophic as well as photomixotrophic cell cultures of this plant were
      characterized with the aim of finding a system for studying the biosynthesis of
      unusual fatty acids. It was found that (Z)-6-octadecenoic acid, petroselinic
      acid, which is the typical constituent fatty acid of triacylglycerols in seeds,
      occurs only in small proportions, if at all, in leaves, roots, and cell cultures
      of parsley. In all lipid classes studied petroselinic acid is accompanied by its
      (Z)-9- and (Z)-11-isomers, oleic and vaccenic acid, respectively. The
      phosphatidylcholines, phosphatidylethanolamines, and triacylglycerols of both
      heterotrophic and photomixotrophic callus cultures contain no petroselinic acid
      but rather oleic and vaccenic acids in equal ratios. Thus, cell cultures of
      parsley appear to be suitable for studying the biosynthesis of vaccenic acid. The
      constituent octadecadienoic acids in the lipids of various tissues and cell
      cultures of parsley consist almost exclusively of the (Z),(Z)-9,12-isomer,
      linoleic acid, which is derived from oleic acid. (Z),(Z)-6,9- and (Z),(Z)-11,14
      Octadecadienoic acids, which could be expected as products of desaturation of
      petroselinic and vaccenic acids, were not found in any of the lipids of organs
      and cell cultures investigated. 

PMID- 24306586
TI  - Light filtering function of bud scales in woody plants.
AB  - Bud scales ofPicea abies (L.) Karst andFagus sylvatica L. selectively transmit
      the incident spectrum of electromagnetic radiation. It was shown that the scales
      absorb almost all radiation below 600 nm. Only the red and far-red light which is
      reduced to 0.01-2% reaches the apical domes. The center of a beech bud receives
      0.11% and the center of a spruce bud 0.84% of the incident 300-2,000 nm light. 

PMID- 24306585
TI  - HCO 3 (-) and OH (-)transport across the plasmalemma ofChara : Spatial resolution
      obtained using extracellular vibrating probe.
AB  - Internodal and whorl (branch) cells of the green alga,Chara corallina Klein ex
      Willd., em. R.D.W., were studied with the extracellular vibrating probe for
      measuring transmembrane ion currents, and with an extracellular pH microprobe for
      measuring the surface pH profile. Bands of positive inward current (OH(-) efflux)
      1-3 mm wide were separated by wider bands of outward current (HCO 3 (-) influx)
      along the length of the cell. The measured peaks of inward current ranged from 20
      to 60 MUA cm(-2) (98 MUm from the cell surface) which would correspond to a
      surface ionic flux of 270-800 pmol cm(-2) s(-1). The peaks of outward current
      (HCO 3 (-) influx) ranged from 10 to 30 MUA cm(-2) which would correspond to a
      surface ionic flux of 140-400 pmol cm(-2) s(-1). The inward current bands matched
      the regions of surface alkalinity very well. The outward current (HCO 3 (-)
      influx) was reduced at least 10-fold in low-HCO 3 (-) medium, with a commensurate
      readjustment in the strength and pattern of inward current (OH(-) efflux).
      (Although these experiments involved a manipulation of the external pH, it is
      felt that the main adjustment in current patterns was in response to the
      reduction in exogenous HCO 3 (-) ). The presence of the vibrating probe perturbed
      the inward current region when vibrating with a 26-MUm amplitude, but this
      perturbation was eliminated when a 7-MUm amplitude was used. The perturbation was
      usually observed as a reduction in the number of inward current peaks with an
      increase (approximate doubling) in the amplitudes of the one or two remaining
      peaks. Both the inward and outward currents were light-dependent, falling off
      within seconds of light removal. 

PMID- 24306587
TI  - Relationship of photocarotenogenesis to other behavioural and regulatory
      responses inPhycomyces.
AB  - The effect of light on carotene accumulation was studied by analyzing the beta
      carotene content of 4-alpha-old mycelia continuously exposed to illumination of
      different intensities. The wild-type, mutants defective in phototropism, mutants
      defective in carotene regulation, and newpic mutants specifically defective for
      photocarotenogenesis were examined. The results indicate that
      photocarotenogenesis depends on a single sensory pathway which shares its earlier
      steps (governed by genesmadA andmadB) with the sensory pathway for phototropism.
      It shares its later steps (probably governed by genescarA andpicB) with one of
      the pathways for carotene regulation, and includes at least one specific step
      (governed by genepicA) not known to be involved in other responses. 

PMID- 24306588
TI  - Properties and regulation of adenosine 5'-phosphosulfate sulfotransferase from
      suspension cultures ofNicotiana sylvestris.
AB  - The properties and the regulation of adenosine 5'-phosphosulfate sulfotransferase
      extracted from cell suspension cultures ofNicotiana sylvestris was investigated.
      Optimal adenosine 5'-phosphosulfate sulfotransferase activity was obtained from
      the cells by extraction with 0.1 M tris-HCl, pH8.0, containing 2 M MgSO4 and 10
      mM dithioerythritol. The K m for adenosine 5'-phosphosulfate in the
      sulfotransferase reaction was about 11 MUM. Adenosine 5'-phosphosulfate in
      concentrations above 50 MUM were inhibitory. The extratable adenosine 5'
      phosphosulfate sulfotransferase activity decreased during cultivation with
      sulfate as the sole sulfur source, but after about 3 days it reached a constant
      level (50 to 100 nmol activated sulfate transferred h(-1) mg(-1) protein) which
      was maintained for at least 24 h. Addition of 0.5 mM cysteine to the culture
      medium decreased the extractable adenosine 5'-phosphosulfate sulfotransferase
      activity and blocked growth completely. With 0.1 mM cysteine an enzyme level of
      about 10% of the initial value was reached within 6 to 12 h without significant
      inhibition of growth. The added cysteine was absorbed rapidly and after 24 h
      cysteine could no longer be detected in the medium. Before the cysteine was
      completely depleted, the activity of adenosine 5'-phosphosulfate sulfotransferase
      started to increase, reaching ultimately a level which was comparable to the
      initial value. 

PMID- 24306589
TI  - Propagated waves induced by gradients of physiological factors within plasmodia
      ofPhysarum polycephalum.
AB  - Plasmodia ofPhysarum polycephalum were analyzed with the aid of cinematography
      and the infrared reflection technique for characterization of the phase behavior
      of their oscillating contraction activity, with special emphasis placed on the
      effects of temperature gradients. In response to temperature gradients, phase
      gradients were documented cinematographically as well as by infrared
      registration. A quantitative evaluation of the cinematographically recorded
      phenomena was carried out with the aid of streak photography. The phase gradient
      is directed across the region of the temperature gradient with a delay in phase
      toward the colder side. The correspondingly generated waves are as short as 1 mm
      and are propagated toward the colder region. A comparison of these waves with the
      known "flickering" phenomena in cinematographic films reveals a common nature of
      both. 

PMID- 24306590
TI  - Manganese superoxide dismutase from a higher plant : Purification of a new Mn
      containing enzyme.
AB  - A manganese-containing superoxide dismutase (EC 1.15.1.1) was purified to
      homogeneity from a higher plant for the first time. The enzyme was isolated
      fromPisum sativum leaf extracts by thermal fractionation, ammonium sulfate
      salting out, ion-exchange and gel-filtration column chromatography, and
      preparative polyacrylamide gel electrophoresis. Pure manganese superoxide
      dismutase had a specific activity of about 3,000 U mg(-1) and was purified 215
      fold, with a yield of 1.2 mg enzyme per kg whole leaf. The manganese superoxide
      dismutase had a molecular weight of 94,000 and contained one g-atom of Mn per mol
      of enzyme. No iron and copper were detected. Activity reconstitution experiments
      with the pure enzyme ruled out the possibility of a manganese loss during the
      purification procedure. The stability of manganese superoxide dismutase at-20
      degrees C, 4 degrees C, 25 degrees C, 50 degrees C, and 60 degrees C was studied,
      and the enzyme was found more labile at high temperatures than bacterial
      manganese superoxide dismutases and iron superoxide dismutases from an algal and
      bacterial origin. 

PMID- 24306591
TI  - Steady state osmotic adaptation inUlva lactuca.
AB  - The effects of hyper- and hypo-saline stresses on the levels of various inorganic
      and organic solutes inUlva lactuca have been recorded. Hypoosmotic stress
      decreased the tissue concentration of K(+), Na(+) and Cl(-) while hyper-osmotic
      stress caused a transient increase in Na(+) and a stable accumulation of K(+) and
      Cl(-). The tissue content of beta-dimethylsulphoniopropionate (beta
      dimethylpropiothetin) responded to changes in salinity. The time course of
      hypersaline stress showed the beta-dimethylsulophoniopropionate concentration
      rose as the Na(+) level fell. The levels of free sugars and amino acids,
      including proline, were relatively low in this alga and did not appear to be
      important in osmotic adjustment. The possibility that tertiary sulphonium dipolar
      ions have an analogous role in some algae to glycinebetaine and possibly other
      quaternary nitrogen compounds in higher plants as cytoplasmic osmotica is
      discussed briefly. 

PMID- 24306592
TI  - Fatty acid synthesis by isolated chromoplasts from the daffodil. Energy sources
      and distribution patterns of the acids.
AB  - 1. Fatty acid synthesis in isolated intact chromoplasts from [1-(14)C]acetate was
      made possible by using ATP, ADP (via adenylate kinase), and, with decreasing
      efficiency, UTP, CTP, and GTP as energy sources. 2. The glycolytic path from
      dihydroxyacetone phosphate to acetyl-CoA operates within the chromoplasts. The
      glycolytic intermediates, especially 2-phosphoglycerate and phosphoenolpyruvate,
      served as very effective energy donors for fatty acid synthesis by
      phosphorylating the endogenous adenine nucleotide pool. 3. In the presence of
      exogenous ATP or ADP, appreciable amounts of in vitro formed fatty acids were
      found as acyl-CoA and subsequent products, mainly phosphatidylcholine. When other
      energy sources were used most of the acids formed were in the free form, and to a
      minor extent, in the phosphatidic acid and diacylglycerol fractions. Similar
      results have recently been reported for spinach chloroplasts (Kleinig and
      Liedvogel 1979, FEBS Lett.101, 339-342). 

PMID- 24306593
TI  - Phosphate translocator and adenylate translocator in chromoplast membranes.
AB  - It is shown by the criteria of saturation kinetics, specificity, and inhibition
      experiments that chromoplast membranes from the daffodil flower contain a
      phosphate translocator for the counter-exchange of phosphate, and 3
      phosphoglycerate, as well as phosphoenolpyruvate; they also contain an adenylate
      translocator. This is the first report on the occurrence of these translocators
      in non-green plastids. Both translocators exhibit certain dissimilar properties
      when compared to the corresponding systems of chloroplasts. The transport rates
      of both translocators are sufficient to allow a prominent fatty acid synthesis in
      isolated chromoplasts when C3 intermediates of the glycolytic pathway or adenine
      nucleotides are used as energy sources. 

PMID- 24306594
TI  - Fluence response relationship of carotenogenesis inNeurospora crassa.
AB  - The fluence response of the blue light induced carotenoid synthesis inNeurospora
      is biphasic. Using fluence rates between 0.3 and 40 Wm(-2), increasing
      illumination times beyond 16 min (at 20 degrees C) result in a second rise of the
      amount of carotenoids synthesized in the subsequent dark period. On altering the
      temperature, the transition point to the second phase of the response is shifted
      to shorter/longer illumination periods with increasing/decreasing temperature,
      respectively. The transition point can also be shifted by administering high
      fluence rates of near UV light: The start of the second phase is already
      triggered after an irradiation time of 2 min. The findings suggest that elements
      of the transduction sequence become depleted and senstivity recovers in a
      temperature-dependent process. The biphasic response and the effects of UV light
      are discussed in relation to the transduction mechanism and to the ecological
      significance. 

PMID- 24306595
TI  - Synchronization and signal transmission in protoplasmic strands ofPhysarum :
      Reaction to varying temperature gradients.
AB  - Isolated protoplasmic strands ofPhysarum polycephalum, mounted as a trapeze, show
      synchronous contraction activities when the isometric tension development of both
      arms of the trapeze is measured independently of each other. This phase
      regulation can be experimentally disturbed by temperature changes. Within a
      permanent gradient, however, the phases become resynchronized. The maximal
      temperature gradient between both arms allowing a phase resynchronization was
      approximately 9 degrees  C along a distance of 25 mm. The transmission of the
      signal along the middle piece of the trapeze (which, as the connecting part of
      both arms, is responsible for signal transmission in phase synchronization) can
      be influenced by temperature changes. The minimal temperature allowing a signal
      transmission is 15 degrees  C, the maximal temperature approximately 29 degrees 
      C. A morphological investigation of protoplasmic strands mounted as trapezes
      revealed that the normal architecture of the objects is not influenced by the
      experimental trapeze arrangement. Permanent thermal gradients induce thermotactic
      reactions, i.e., a preferred protoplasmic mass transport into one arm of the
      trapeze. This leads, after several hours, to a morphological asymmetry of the
      trapeze. In spite of the fact that this reaction limits the temporal use of
      trapezes within thermal gradients to 2-3 h, the capacity of such strands for
      phase regulation is not hindered. Thermal gradients are suitable methods for
      studying the unknown phase-regulating factor and its transmission. As criteria
      for an intact pathway of signal transmission, the capacity of the trapeze arms to
      resynchronize as well as to maintain synchronization within a thermal gradient
      can be used. 

PMID- 24306596
TI  - Photorespiration and beta-carboxylation in brown macroalgae.
AB  - Photorespiration has been assayed in a variety of marine macroalgae by the
      Warburg oxygen inhibitory effect and the percentage(14)C-labeling of glycine and
      serine. It was found that particularly the members of the brown macroalgae
      examined, such asFucus andLaminaria (Phaeophyceae), show a rather weak response
      to high O2 partial pressure. This observation is attributed to the appreciably
      high potential for beta-carboxylation via PEP-carboxykinase, generally occurring
      in brown seaweeds. 

PMID- 24306597
TI  - Somatic hybrids between unilateral cross-incompatible Petunia species.
AB  - Somatic hybrid plants regenerated following the fusion of leaf mesophyll
      protoplasts of Petunia parodii with those isolated from a cell suspension of
      albino P. inflata. These two species exhibit a unilateral cross-incompatability
      with a pre-zygotic mode of reproductive isolation preventing hybridizations with
      P. inflata as the maternal parent. Selection of somatic hybrids relied on the
      fact that unfused or homokaryon protoplasts of P. parodii did not develop beyond
      the cell colony stage while those of the putative somatic hybrids and albino P.
      inflata parent produced callus. Green somatic hybrid calluses were readily
      identified against the white background of P. inflata following complementation
      to chlorophyll synthesis proficiency and continued growth in hybrid cells.
      Shoots, and ultimately flowering plants, were identified as somatic hybrids based
      on their floral morphology and colour, chromosome number and the fact that they
      segregated for parental characters. The frequency of somatic hybrid production
      was comparable to that previously established for two sexually compatible Petunia
      species. 

PMID- 24306598
TI  - An effective chemical mutagenesis procedure for Petunia hybrida cell suspension
      cultures.
AB  - By using mercury(II)-chloride (HgCl2) and Dl-6-fluorotryptophan (6FT) as positive
      selection conditions we were able to show that N-methyl-N'-nitro-N
      nitrosoguanidine (NG) is an effective mutagen for Petunia hybrida suspension
      cells.A number of the 205 calli resistant to HgCl2 and 17 calli resistant to 6FT
      were isolated. The highest mutation frequency was 1.0 x 10(-5) and 2.0 x 10(-6)
      for HgCl2 and 6FT, respectively. A preliminary characterization of the mutants is
      presented.A significant increase in the number of drug-resistant calli was only
      obtained at NG-concentrations (5-40 MUg/ml) that had no observable effect on the
      survival of the mutagenized cultures. 

PMID- 24306599
TI  - Use of amino acid analogue-resistant cell lines for selection of Nicotiana
      sylvestris somatic cell hybrids.
AB  - Nicotiana sylvestris cell lines resistant to the amino acid analogues S-2
      aminoethyl-cysteine (AEC(R)), or 5-methyl-tryptophan (5MT(R)), were isolated in
      suspension culture. Assuming these resistances to be dominant, we have attempted
      to determine if such variant cell lines can be used to select double resistant
      somatic cell hybrids. A total of 1.8 * 10(4) control calli from mixed AEC(R) and
      5MT(R) protoplasts, and AEC(R) and 5MT(R) homokaryotic fusions were placed on
      double analogue selection, but none survived. Eight somatic hybrid calli (0.8%),
      able to grow without inhibition on the double analogue selection medium, were
      obtained after AEC(R) + 5MT(R) protoplast fusion. These were further determined
      as hybrids on the basis of resistance level, chromosome number, and chlorophyll
      content, all characteristics differing in the parental cell lines. 

PMID- 24306600
TI  - Differences in red cell shape of two inbred chicken lines.
AB  - Comparison of two inbred chicken lines (Fx > 99.9%) revealed significant
      differences in shape of the red blood cells (RBC). The length-width index was
      lower for both sexes in IC-line (1.46) when compared to CB-line chickens (1.88).
      Phenotypic expression of this character in F1 hybrids and both backcross groups
      corresponded to the common manifestations of the metric parameters. The index in
      F1 hybrid chickens deviated from intermediate values with the dominant tendency
      to oval RBC. An analysis of the segregating first backcross generation chickens
      did not show any association between RBC shape and the genotype in the blood
      group systems B, C, I, and D and the IgG allotypes. The differences in RBC shape
      were probably not associated with the survival of RBC in the blood circulation. 

PMID- 24306601
TI  - Participation of the intracellular enzymes in the control of mutational processes
      : Part 4: the role of UV-specific endonuclease and medium composition in the
      induction of genic mutations in Escherichia coli.
AB  - The influence of UV-specific endonuclease and medium composition on the frequency
      and spectrum of genic mutations in Escherichia coli KI2 uvr (+) (with normal
      repair enzymes) and urv A6 (defective in UV-specific endonuclease) was studied.
      Mutations at the locus glu (gene controlling assimilation of glucose) were
      induced by ultra-violet irradiation and hydroxylamine treatment. To identify
      mutant colonies, triphenyl tetrazolium chloride (TTC) was added to the medium
      since it coloured the mutant colonies bright crimson and readily permitted
      distinction between pure mutant clones (complete mutations) and mixed clones
      (mosaic or sector mutations).A maximum mutation frequency after UV-irradiation
      was observed in E. coli uvr (+) cells but not in the E. coli uvr A6 strain. The
      curve of mutagenesis with a maximum was found in both studied strains after
      treatment by hydroxylamine which did not cause DNA damage recognized by UV
      specific endonuclease.The highest frequency of mutations (at the point of
      maximum) in the series of experiments with enriched growth medium was almost 10
      times higher than in the series of the experiments with poor medium.It was
      established that in bacteria with normal repair enzymes the frequency of complete
      mutations was higher than the frequency of mosaic mutations. It was also observed
      that the rate of UV-mutagenesis was higher in the case of E. coli uvr (+).The
      study of the distribution of mosaic mutant sectors in experiments with bacteria
      suspended in either a nutrient broth or a buffer during UV-irradiation revealed
      that the size of mutant sectors was rather variable and that the differences in
      the number of nucleoids per cell did not always determine the distribution of
      mutant sector sizes. 

PMID- 24306602
TI  - Doubled haploids for estimating genetic variances in presence of linkage and gene
      association.
AB  - The effect of gene association (or dispersion) and linkage on the estimation of
      genetic variances in a diallel experiment involving doubled haploid lines is
      evaluated. It is shown that the estimates of the additive and the additive X
      additive genetic variances, as obtained by Choo et al. (1979), are biased if
      genes are linked or are not independently distributed in the parents. However,
      this bias only occurs in the presence of interaction between homozygous loci.
      Gene association (or dispersion) and linkage, if present, can be detected by
      comparing the parental vs the crosses mean, the parental vs the doubled haploid
      lines variance, and the among vs the within crosses variance. 

PMID- 24306603
TI  - Nucleotide polymorphism in chloroplast dna of Nicotiana debneyi.
AB  - EcoR1 restriction endonuclease analysis of chloroplast DNA isolated from several
      distinct populations of Nicotiana debneyi has revealed a naturally occurring
      polymorphism. The chloroplast DNA of seven of the nine populations analysed
      possessed an additional EcoRl site. The origin of the additional restriction
      endonuclease fragments was confirmed by hybridisation of [(32) P]-cRNA to
      fractionated EcoRl restricted chloroplast-DNA fragments adsorbed to
      nitrocellulose filters. Reciprocal f1 hybrids between plants carrying the variant
      chloroplast-DNA's confirmed maternal inheritance of chloroplast-DNA. 

PMID- 24306604
TI  - Haploidy from Hordeum interspecific crosses : Part 2: dihaploids of H.
      brachyantherum and H. depressum.
AB  - Interspecific crosses of Hordeum brachyantherum (2n = 28) and H. depressum (2n =
      28) with H. bulbosum (2n = 14 or 28) and H. vulgare (2n = 14 or 28) were made.
      Crosses between brachyantherum and diploid bulbosum resulted in dihaploids (2n =
      14) of brachyantherum and hybrids (2n = 21), whilst the crosses of brachyantherum
      by tetraploid bulbosum or vulgare gave hybrid progeny. Similarly, crosses between
      H. depressum and diploid bulbosum resulted in dihaploids (2n = 14) of depressum
      and hybrids (2n = 21), whereas depressum by tetraploid bulbosum or vulgare
      invariably produced hybrids.Cytological observations on 12 day old embryos
      obtained from these crosses revealed chromosome variability down to 14 in crosses
      with diploid bulbosum indicating thereby that chromosome elimination leads to
      haploid formation. Embryonic cells from the brachyantherum by diploid vulgare
      cross also exhibited a certain degree of chromosomal instability as
      micronuclei.The results indicate that the ratio of parental genomes in the zygote
      determines whether haploids or hybrids will be produced in crosses of
      brachyantherum or depressum with bulbosum. Furthermore, brachyantherum appears to
      be more efficient in eliminating bulbosum chromosomes in comparison with
      depressum. 

PMID- 24306605
TI  - Cell frequencies of green somatic-variations in the tl chlorophyll mutant of
      Nicotiana tabacum var 'Samsun'.
AB  - The chlorophyll deficient tl mutant of Nicotiana tabacum var 'Samsun' expresses
      green, clear and twin, green and clear somatic variations spontaneously on leaves
      at a low frequency. This character is maintained after both vegetative
      multiplication and sexual reproduction. However a very important phenotypic
      variability in the capacity for somatic variation appears in in vitro bud
      neoformations from leaf fragments of tl/tl homozygous plants. This variability is
      observed in the type of variations and the variation pattern, defined as the
      frequency and size of the variant areas.The present work was aimed at determining
      both the cell frequencies of the events which lead to the somatic variation and
      the preferential sequence of leaf initial development during which these
      frequencies are at a maximum. It was limited to plant populations with very
      different patterns for green variations, some having a high frequency of large
      variation, others having a high frequency of small variations. They were compared
      with a population of control plants having a low frequency.In the case of plants
      having a high frequency of large green variations, the events leading to somatic
      variation occurred between the twenty-first and the twelfth cell cycles preceding
      the end of the initial division phase, the maximum cell frequencies being in the
      seventeenth and sixteenth cycles. The maximum frequencies appeared extremely
      high, being on average about 10(-2). In plants with a high frequency of small
      green variations the event occurred between cell cycles nine and one, with mean
      frequencies of 10(-3) but without any clearly marked maximum. In the low
      frequency control plants the event also took place during the last ten cell
      cycles but with decreasing frequencies from 10(-4) to 10(-7).The frequency and
      the starting period of the cell events leading to somatic variation are closely
      dependent on the state of the cell. This is, on the one hand, strictly linked to
      the physiology of the plant and, on the other, closely correlated with the stage
      of differentiation, which may vary according to the genetic back ground of the
      leaf initial cells.The results are discussed in relation to comparable
      observations and the relevant interpretations made on other instability mutants. 

PMID- 24306606
TI  - Identification of a high-molecular-weight subunit of glutenin whose presence
      correlates with bread-making quality in wheats of related pedigree.
AB  - The subunit composition of glutenin was analysed by SDS-polyacrylamide-gel
      electrophoresis using two varieties of contrasting pedigrees. 'Maris Widgeon', a
      variety of good bread-making quality, was shown to contain 2 glutenin subunits
      not present in 'Maris Ranger', a much higher yielding variety that is unsuitable
      for making bread. A third subunit was only found in 'Maris Ranger' glutenin. To
      determine if any of these subunits are directly related to bread-making quality,
      60 randomly-derived F2 progeny from a 'Maris Widgeon' x 'Maris Ranger' cross were
      analysed for bread-making quality and for glutenin subunit composition. A strong
      correlation was demonstrated between the presence of one of the two subunits
      inherited from 'Maris Widgeon', and quality. This subunit (termed subunit 1
      glutenin) had an approx. mol. wt. of 145,000. It was also found in 'Maris
      Freeman', a bread-making variety selected from the same cross previously made in
      1962. In further crosses involving 'Maris Widgeon' or its descendants, more bread
      making varieties have been produced in the last decade at the Plant Breeding
      Institute, Cambridge and all but one have inherited glutenin subunit 1. The
      subunit has been traced back through 'Holdfast' to 'White Fife', a Canadian hard
      spring wheat of excellent breadmaking quality. Some 67 varieties were screened
      for the presence of glutenin subunit 1 and it was found in 31% of them. Several
      unrelated varieties of good bread-making quality did not contain subunit 1
      glutenin. 

PMID- 24306607
TI  - Detection of genic interactions by analyzing the F2 generation of diallel
      crosses.
AB  - The ability of the Hayman and Jinks method of analysis of diallel crosses to
      detect genic interactions was studied in peanuts. Six traits, measured in the F2
      generation of a diallel cross of four cultivars, were analyzed. In F2 analyses of
      the diallel, least squares estimates of variance components D, H1 , H2, F, E,
      were used as an additional criteria for the adequacy of the diallel model. They
      were found to be in substantial agreement with the tests based on Wr and Vr
      values, and probably more reliable. The regression of Wr on Vr was shown to be
      unsuitable to detect 'duplicate gene' type of interactions; it was detected,
      however, by the ratio of the mean within-F2 - family variance and the variance
      among the parents. Using the different criteria, 'duplicate genes' type of
      interactions was detected for two traits, 'complementary genes' type was detected
      for one trait and three traits were found to fit the additive-dominance model
      without any genic interactions. 

PMID- 24306608
TI  - Mode of inheritance of dwarf stature and allelic relationships among various
      spontaneous and induced dwarfs of cultivated rice Oryza sativa L.
AB  - Genetic study of spontaneous and induced dwarfs included the mode of inheritance
      of dwarf stature and the allelic relationships among various dwarfs. Qualitative
      genetic analysis involving crosses of fourteen dwarfs with a common tall variety
      'IARI 11124' showed that the degree of dominance in the F1 hybrids varied with
      the cross. With the exception of the crosses of IARI 6579 and IARI 10560 with the
      tall variety, all crosses exhibited incomplete dominance. The segregation pattern
      in F2 populations of height classes showed dwarfness to be a monogenic recessive
      trait functioning, however, in association with modifier complexes of varied
      strength. From F2 behaviour of all possible crosses involving the fourteen
      different dwarfs, the allelic relationships were deduced. Three major groups of
      dwarfs could be recognised. Group I, comprised of FF 36, IARI 5842, IARI 5906-2B,
      IARI 5923, IARI 10061, IARI 10560 and IARI 11445, was allelic to I-geo-tse and
      Dee-Gee-Woo-Gen with modifiers of predominantly negative effects, while group-2,
      comprised of dwarfs IARI 5901-2, IARI 5924, IARI 6579 and IARI 7312B, was also
      allelic to Dee-Gee-Woo-Gen and I-geo-tse but with large and equal number of
      modifiers of positive and negative effects. The induced mutant, Central Africa
      Mutant (CAM) which constituted the third group seemed to possess a dwarfing gene
      that was non-allelic to those of the above mentioned two groups of dwarfs, with
      equal strength of modifiers of plus and minus effects. Unlike the dwarfs of
      spontaneous origin, which are invariably allelic to 'Dee-Gee-Woo-Gen', the
      induced dwarf was nonallelic. Thus, induced mutagenesis appears to give rise to
      dwarfing genes different from those found in the naturally occurring dwarfs. 

PMID- 24306609
TI  - Sex determination in Sarotherodon (tilapia) : Part 2: the sex ratio as a tool for
      the determination of genotype - a model of autosomal and gonosomal influence.
AB  - The simplest possible model of the sex determination process adding autosomal
      influence to a minimal number of sex chromosomes was developed to explain matings
      of Tilapia (Sarotherodon) species. Eighteen different genotypes, each having two
      autosomes (AA, Aa, or aa) and two sex chromosomes (WX, WY, WW, XY, XX or YY)
      involved in sex determination, are predicted by the theory. Their sex (10 males
      and 8 females) were determined using a series of directed graphs, showing the
      relative strength of the chromosome pairs, developed on the basis of Chen's sex
      ratio results (Chen 1969). This theoretical model predicts eight different sex
      ratios (0?1, 1?3, 3?5, 1?1, 9?7, 5?3, 3?1, 1?0 ???); three of them are not
      predicted by the WXYZ theory. The greatest part of these sex ratios have been
      obtained experimentally in extensive series of crosses between related species of
      Tilapia and their hybrids, carried out by several authors. The theory succeeds in
      explaining all of Chen's results, including those ratios 5?3 and 0?1 seen in
      certain crosses but not predicted by the WXYZ theory. The importance of the
      autosomes is seen in comparisons of the genotype pairs (AaWY, aaWY), (AaXY, aaXY)
      and (AAWW, AaWW) in which the first genotype in each case is male while the
      second is female as proven by the sex ratio results. The members of the pair
      differ only in the substitution of one autosome for the other. To test the
      theory, experiments consisting of hormonal sex reversion and a series of crosses
      are proposed. Finally, theoretical and practical implications of the theory are
      discussed. 

PMID- 24306611
TI  - Pro-life, pro-choice.

PMID- 24306610
TI  - Cytogenetic behaviour and phosphate and potassium content in desynaptic pearl
      millet.
AB  - Continued inbreeding by self pollination resulted in a proportion of sterile
      plants in some families of the inbred line IP 1475 of Pennisetum americanum (L.)
      Leeke. Cytological examinations of the sterile plants revealed mild to extreme
      desynapsis and also chromosome fragmentation in some plants. Segregation ratios
      in the selfed families did not fit into any simple Mendelian ratio; however, in
      one F2 family of the cross desynaptic x normal, segregation into 15 normal: 1
      desynaptic was observed. Plants from a segregating family were classified as
      normals, desynaptics with 2-6 univalents, desynaptics with 2-10 univalents,
      desynaptics with 10-14 univalents and desynaptics with chromosome fragmentation.
      Estimation of the content of phosphate and potassium from the flag leaves did not
      reveal significant differences between the five groups of plants. 

PMID- 24306612
TI  - An essay on psychotherapy and religion.
AB  - Cultural innovation by thinkers of the early twentieth century created an
      intellectual impasse between competing understandings of religion. Religion was
      understood as either transcendence and the sacred (e.g., Otto) or as fantasy and
      projection (e.g., Freud). Whether a cooperative symbiosis of these orientations
      toward religion can be achieved is the central and unresolved issue of this
      paper. "Examined experience" is considered within religious studies and
      psychotherapy. Although not conclusive, the argument is that examined experience
      is a means by which the desired symbiosis can be achieved. The essay is personal
      in that it reflects the author's struggle for understanding, especially as
      Western (e.g., Christian) and Eastern (e.g., Zen) experiences are examined. 

PMID- 24306613
TI  - Psychoanalytic approaches to biblical religion.
AB  - A brief look at four studies of biblical religion from a psychoanalytic point of
      view (spanning the time from Freud'sMoses and Monotheism to the present) alerts
      us to the many ways biblical religion both reflects and mediates the dawning
      realization that for the well-being of humanity it is of decisive importance that
      sons do (in spite of all emotional obstacles) identify with their fathers and
      fathers do find ways of loving and caring for their sons (the eldest son in
      particular). 

PMID- 24306614
TI  - Today's women and depression.
AB  - The author suggests that women in our society are more vulnerable to depression
      than ever before. A brief review of four psychoanalytical approaches to treatment
      and the religious care of the depressed woman are presented. The Book of Ruth is
      used as a case study of a woman's reactive depression. 

PMID- 24306615
TI  - Forest lights: Notes on the conceptualization of the unconscious.
AB  - Using the metaphor of lights appearing unexplained in the night, the author
      argues for a conceptualization of the unconscious based on a posture of trust and
      acceptance rather than one of fear and explanation. 

PMID- 24306616
TI  - Existential perspective in the thought of Carl Jung.
AB  - It is argued that there is a significant existential perspective in the thought
      of Carl Jung. Similarities and differences with some of the views of Jean Paul
      Sartre are explored as a way of developing this perspective and to show how a
      philosophy of a man might be developed drawing from both sources. Jung is shown
      to be in disagreement with Sartre in defending an idea of a determinate human
      nature, describing the self in a developmental way, and in not claiming that
      human freedom is absolute or unconditioned. Nevertheless, the Jungian concept of
      individuation is similar to Sartre's ideal of authenticity, in that both focus on
      the goal of achieving meaningful existence through development of inner
      resources, creative exercise of freedom, and overcoming self-deception. 

PMID- 24306617
TI  - Psychotherapy and the locus of control.
AB  - Underlying various actions of both the therapist and the patient are expectations
      about the measure to which an individual's experiences are the product of
      powerful external forces or of the person's own actions and decisions. While most
      of our anthropological theories support the notion that a person's experience is
      subject to an external locus of control, neither that view nor the opposite
      emphasizing freedom and autonomy is adequate for the therapeutic enterprise.
      THere are elements of truth in both positions that ned to be incorporated in
      therapeutic expectations if the enterprise is to proceed in an orderly fashion. 

PMID- 24306618
TI  - Use of inertial measurement units to assess age-related changes in gait
      kinematics in an active population.
AB  - To study mobility in older populations it can be advantageous to use portable
      gait analysis systems, such as inertial measurement units (IMUs), which can be
      used in the community. To define a normal range, 136 active subjects were
      recruited with an age range of 18 to 97. Four IMUs were attached to the subjects,
      one on each thigh and shank. Subjects were asked to walk 10 m at their own self
      selected speed. The ranges of motion of thigh, shank, and knee in both swing and
      stance phase were calculated, in addition to stride duration. Thigh, shank, and
      knee range of movement in swing and stance were significantly different only in
      the > 80 age group. Regressions of angle against age showed a cubic relationship.
      Stride duration showed a weak linear relationship with age, increasing by
      approximately 0.1% per year. 

PMID- 24306619
TI  - Comparative study of one-stitch versus Lich-Gregoir ureterovesical implantation
      for kidney transplants.
AB  - OBJECTIVE: To compare the outcomes of standard Lich-Gregoir technique and a
      modified one-stitch technique of ureteroneocystostomy in renal transplantation.
      PATIENTS AND METHODS: Data from 645 transplant recipients by two different
      ureteroneocystostomy techniques were retrospectively reviewed at the first
      Affiliated Hospital, Medical College of Xi'an Jiaotong University, between
      January 2002 and December 2007. RESULTS: There were 418 recipients in the Lich
      Gregoir group and 227 in new one-stitch group. The overall ureteral complication
      rate for new one-stitch technique was 19.8 % (n = 45) as opposed to 15.79 % (n =
      66) for the Lich-Gregoir technique. No significantly different rate of ureteral
      complications occurred in two groups (P > 0.05). In comparison, there was a
      higher proportion of hematuria at the limit of statistical significance in new
      one-stitch group (P < 0.05). Average operative time for the modified one-stitch
      and Lich-Gregoir techniques was 8.8 +/- 1.4 and 21.9 +/- 6.1 min, respectively (P
      < 0.05). Urinary tract infections, delayed graft function and rejection rates
      were not significantly different between the two groups (P > 0.05). CONCLUSION:
      Although the modified one-stitch technique may predispose patients to higher
      rates of hematuria, it has no significant difference in ureteral complications
      compared with the Lich-Gregoir group. Based on this large series and data
      analyses, we believe that this new technique will become one of our multiple
      choices in our setting.

PMID- 24306620
TI  - New technique for prostate volume assessment.
AB  - PURPOSE: The prostate-specific antigen density (PSAD) helps distinguish between
      benign prostatic hyperplasia (BPH) and prostate cancer. Accurate prostate volume
      (PV) assessment is necessary for PSAD calculation and both BPH diagnosis and
      treatment response monitoring; therefore, accurate PV measurement is increasingly
      becoming an essential step in the urology. METHODS: Magnetic resonance imaging
      was used for PV estimation. A new technique based on single-class support-vector
      machines (S SVM) for accurate PV estimation was realized. Three estimation
      methods were compared; method 1: planimetry (reference), method 2: S SVM based,
      and method 3: prolate ellipsoid. RESULTS: Method 1 and method 2 depict a strong
      correlation (Spearman's rank correlation coefficient rho = 0.965, p > 0.001). The
      interrater reliability for method 1 and method 2 readings as expressed by the
      intraclass correlation coefficient (ICC) was 0.975 (p > 0.001). Comparison
      between method 3 and the two other methods shows rho = 0.873 (p > 0.001), and rho
      = 0.795 (p > 0.001), respectively. ICC was 0.54 and 0.505, respectively. The mean
      difference between method 1 and method 2 was -0.05 ml. The limits of agreement
      with the 95 % confidence interval were -3.8 to 3.7 ml. Comparing method 3 and the
      two other methods shows a worse agreement with mean difference of 8.6 ml (95 %
      confidence interval of 1.0-16.2 ml) and 8.6 ml (95 % confidence interval of -0.7
      to 18.0 ml), respectively. CONCLUSIONS: The prostate volumes obtained by our
      technique agreed excellently with the planimetry (reference) method. This new
      technique would be clinically useful for urologists in prostate volumetric
      analysis.

PMID- 24306621
TI  - Varying electronic structural forms of ruthenium complexes of non-innocent 9,10
      phenanthrenequinonoid ligands.
AB  - Bis(acetylacetonato)ruthenium complexes [Ru(acac)2(Q1-3)], 1-3, incorporating
      redox non-innocent 9,10-phenanthrenequinonoid ligands (Q1 = 9,10
      phenanthrenequinone, 1; Q2 = 9,10-phenanthrenequinonediimine, 2; Q3 = 9,10
      phenanthrenequinonemonoimine, 3) have been characterised electrochemically,
      spectroscopically and structurally. The four independent molecules in the unit
      cell of 2 are involved in intermolecular hydrogen bonding and pi-pi interactions,
      leading to a 2D network. The oxidation state-sensitive bond distances of the
      coordinated ligands Q(n) at 1.296(5)/1.289(5) A (C-O), 1.315(3)/1.322(4) A (C-N),
      and 1.285(3)/1.328(3) A (C-O/C-N) in 1, 2 and 3, respectively, and the well
      resolved (1)H NMR resonances within the standard chemical shift range suggest DFT
      supported variable contributions from valence formulations [Ru(III)(acac)2(Q(-))]
      (spin-coupled) and [Ru(II)(acac)2(Q(0))], respectively. Complexes 1-3 exhibit one
      oxidation and two reduction steps with comproportionation constants Kc~ 10(7)
      10(22) for the intermediates. The electrochemically generated persistent redox
      states 1(n) (n = 0, 1-, 2-) and 2(n)/3(n) (n = 1+, 0, 1-, 2-) have been analysed
      by UV-vis-NIR spectroelectrochemistry and by EPR for the paramagnetic
      intermediates in combination with DFT and TD-DFT calculations, revealing
      significant differences in the oxidation state distribution at the {Ru-Q}
      interface for 1(n)-3(n). In particular, the diminished propensity of the NH
      containing systems for reduction results in the preference for Ru(II)(Q(0))
      relative to Ru(III)(Q(-)) (neutral compounds) and for Ru(II)(Q(-)) over the
      Ru(III)(Q(2-)) alternative in the case of the monoanionic complexes. 

PMID- 24306622
TI  - Problems in studying and defining pubertal events.
AB  - Problems in studying and defining pubertal events during early adolescence are
      examined in this paper. Whether puberty is best characterized as a social
      construction or as a physical event and whether early adolescence is best
      considered a transitional or distinct life period are discussed. Then, the
      markers or life events associated with puberty and possible boundaries of early
      adolescence are considered. Finally, possible models for studying pubertal change
      are discussed, focusing on timing of events, mediated effects, biobehavioral
      interaction, and cumulative risk models.Puberty: The time of life in which the
      two sexes begin first to be acquainted.- Samuel JOhnson. 

PMID- 24306623
TI  - A longitudinal study of moral and ego development in young adults.
AB  - The purpose of this study was to investigate the longitudinal changes in moral
      judgment and ego development in a young adult sample when a concurrent measure of
      verbal ability was used as a statistical control. Sixty-one late adolescents and
      young adults, representing three educational groups, were tested in 1977 and 1979
      on the Defining Issues Tests, a measure of moral judgment (Rest), the Sentence
      Completion Test of Ego Development (Loevinger and Wessler) and Terman's Concept
      Mastery Test, a measure of verbal ability. No group or time differences were
      found in ego development. A significant increase was found between the 1977 and
      1979 moral judgment scores,p<0.05, and between groups at both testing,p<0.001.
      Sex differences were found,p<0.01, with females scoring higher than males, which
      were statistically accounted for by verbal ability. These findings suggest that
      moral development continues into the young adult years and that verbal ability
      may moderate sex differences in moral judgment. 

PMID- 24306624
TI  - Sex differences in intellectual and ego development in late adolescence.
AB  - Perry's scheme of intellectual and ethical development was examined for sex
      differences with respect to areas of identity concern for which sex differences
      have been suggested: occupational choice, interpersonal relationships, and sexual
      identity. The content area of religion and ego development, as measured by
      Loevinger's sentence completion test (SCT), were also examined. Thirty-one
      females and 29 males participated. An interview format which applied Perry's
      unstructured approach to each of the four areas was utilized. Transcribed
      interviews and SCTs were rated blind. Structural as well as content analyses were
      performed. Structural analyses revealed no significant sex differences overall or
      by content area. However, multiple and stepwise regression analyses revealed
      patterns in which male personality processes consistently focused upon
      occupational issues while female processes focused upon interpersonal and sexual
      issues. Ego development was found to be highly correlated with intellectual
      development for men but unrelated for women. Content analyses suggest that women
      focus their interpersonal worlds developmentally upon issues of trust while men
      focus upon issues of rightness. Results are interpreted in the context of recent
      works by Gilligan concerning sex differences in development. 

PMID- 24306625
TI  - Predicting violent behavior in psychiatrically hospitalized boys.
AB  - A naturalistic study of violent behavior in a sample of 100 boys residing within
      an inpatient psychiatric facility is reported. Over 1000 recorded incidents of
      interpersonal aggression were used to explore patterns of male violence in a
      contextually defined setting. Findings include a proportionately greater
      incidence of violence in younger boys. Staff members, particularly males, were
      more likely to be the victims of interpersonal violence, but peers and staff were
      equally likely to be the target of aggressive behavior in general. Observable
      provocation in the social context, the age of the child, and choice of victim
      (staff vs. peer) were found to be important predictors within a logistic
      regression model of violence. An estimate of the predictive utility of a logistic
      model for the occurrence of violence was found to be too low for clinical
      purposes. An application of a descriptive statistical method to collections of
      incidents for five highly aggressive boys yielded idiopathic models of violent
      behavior. Predictive accuracy estimates from these models suggest that
      multivariate description of behavioral data can be a clinically useful tool in
      understanding and possibly preventing violence within defined contexts such as
      residential psychiatric facilities. 

PMID- 24306626
TI  - Use of drugs among Senegalese school going adolescents.
AB  - Though it may appear more severe and dramatic in most industrialized nations,
      drug addiction has also become a matter for concern in some developing nations.
      The problem is even more complex when, prior to the advent of colonialism and the
      adoption of Western values by those countries, there already existed traditional
      forms of drug addiction. This paper examines the attitudes of Senegalese school
      going adolescents to the problem of drug addiction. It describes the nature,
      development, and perception of drug addiction in the country from an historical
      and sociological point of view. It shows the tolerance of Senegalese society
      toward drugs - some were used in traditional medicine - and its rejection of
      "hard" and intermediate drugs, as they are viewed negatively by the society. The
      authors finally analyze the motivations of the drug addicts which also indicate,
      in Africa as in the West, a crisis of identity reflecting a global crisis of
      civilization. 

PMID- 24306627
TI  - Swimming, swarming, twitching, and chemotactic responses of Cupriavidus
      metallidurans CH34 and Pseudomonas putida mt2 in the presence of cadmium.
AB  - To use of microorganisms for bioremediation purposes, the study of their motility
      behavior toward metals is essential. In the present study, Cupriavidus
      metallidurans CH34 and Pseudomonas putida mt2 were used as cadmium (Cd)-resistant
      and -sensitive bacteria, respectively, to evaluate the effects of Cd on their
      motility behaviors. Potassium morpholinopropane sulfonate (MOPS) buffer was used
      to observe the motility behavior of both isolates. Movement of mt2 was less in
      MOPS buffer compared with CH34, likely reflecting the mono-flagellated nature of
      mt2 and the peritrichous nature of CH34. The swimming, swarming, twitching, and
      chemotaxis behaviors of mt2 were greater in the presence of glucose than that of
      Cd. mt2 exhibited negative motility behaviors when exposed to Cd, but the
      opposite effect was seen in CH34. Cd was found to be a chemorepellent for mt2 but
      a chemoattractant for CH34, suggesting that CH34 is a potential candidate for
      metal (Cd) bioremediation. 

PMID- 24306628
TI  - G protein-coupled estrogen receptor-protein kinase A-ERK-CREB signaling pathway
      is involved in the regulation of mouse gubernaculum testis cells by
      diethylstilbestrol.
AB  - The etiology of testicular dysgenesis syndrome is multifactorial and involves
      environmental factors, such as environmental estrogens. Several studies have
      shown that hormonal effects on the gubernaculum may affect testicular descent.
      Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the
      morphology and proliferation of gubernacular cells, but the underlying mechanisms
      remain elusive. In this study, we aimed to determine whether DES may regulate the
      function of gubernaculum testis cells by way of nongenomic effects mediated by G
      protein-coupled estrogen receptor (GPER). We used cultured mouse gubernacular
      testis cells to demonstrate that GPER is expressed in gubernaculum testis cells.
      Erk1/2 inhibitor PD98059, PKA inhibitor H89, and Src inhibitor PP2 relieved DES
      induced inhibition of gubernaculum testis cell proliferation, but ER inhibitor
      ICI 182780 had no effects on DES-induced inhibition of gubernaculum testis cell
      proliferation. In addition, we found that DES induced the activation of CREB
      downstream of PKA, Src, and ERK1/2 in these cells. These data suggest that the
      effects of DES on mouse gubernaculum testis cells are mediated at least partially
      by GPER-protein kinase A-ERK-CREB signaling pathway. 

PMID- 24306629
TI  - Coexistent dermatofibrosarcoma protuberans and anticonvulsant-induced cutaneous
      lymphoid hyperplasia: diagnostic challenge.
AB  - A 60-year-old African-American male patient with a history of seizures,
      developmental delay, long history of behavioural issues with psychotic episodes,
      heart, liver, thyroid and kidney diseases presented for evaluation of a right
      neck skin lesion. Physical examination revealed a shiny purplish-red plaque on
      the right neck and a thin pink plaque on the posterior neck. The lesions were
      similar in appearance, but different enough to warrant skin biopsy of each.
      Pathology demonstrated mycosis fungoides (MF) on the right neck and
      dermatofibrosarcoma protuberans (DFSP) on the posterior neck. The identification
      of two rare conditions made us reconsider our diagnosis. After further review,
      the right neck skin lesion was thought to be anticonvulsant-induced cutaneous
      lymphoid hyperplasia, not MF. This case demonstrates how insufficient skin biopsy
      can have significant clinical consequences. Biopsy of the right neck only would
      have overlooked a DFSP and incorrectly given the patient a diagnosis of MF. 

PMID- 24306631
TI  - Quetiapine-induced manic episode: a paradox for contemplation.
AB  - A 24-year-old man with bipolar disorder who was started on quetiapine as an
      adjunct to valproate (mood stabiliser) after a depressive episode switched to a
      manic episode while on the drug. The manic episode resolved following the
      withdrawal of quetiapine. This case illustrates the rare possibility of
      quetiapine emergent manic episode which a clinician needs to be aware of in the
      context of the management of bipolar disorders. 

PMID- 24306630
TI  - Chronic Propionibacterium acnes prosthesis joint infection manifesting as a large
      abscess with gas, without prosthesis loosening.

PMID- 24306632
TI  - An older man with a rare cause of heart failure.

PMID- 24306633
TI  - Kinetic mechanism of NADP-malic enzyme from maize leaves.
AB  - The kinetic mechanism of NADP-dependent malic enzyme purified from maize leaves
      was studied in the physiological direction. Product inhibition and substrate
      analogues studies with 3' aminopyridine dinucleotide phosphate and tartrate
      indicate that the enzyme reaction follows a sequential ordered Bi-Ter kinetic
      mechanism. NADP is the leading substrate followed by L-malate and the products
      are released in the order of CO2, pyruvate and NADPH. The enzyme also catalyzes a
      slow, magnesium-dependent decarboxylation of oxaloacetate and reduction of
      pyruvate and oxaloacetate in the presence of NADPH to produce L-lactate and L
      malate, respectively. 

PMID- 24306634
TI  - An in vivo analysis of photosynthesis during short-term O3 exposure in three
      contrasting species.
AB  - The depressions of photosynthetic CO2 uptake following O3 exposures of 200 and
      400 nmol mol(-1) for between 4 and 16 h were compared between Pisum sativum,
      Quercus robur and Triticum aestivum, and the potential causes of change
      identified in vivo. Photosynthetic change was examined by analysis of CO2, O2, O3
      and water vapour exchanges together with chlorophyll fluorescence in controlled
      environments. Under identical fumigation conditions, each species showed very
      similar rates of O3 consumption. The light-saturated rate of CO2 uptake showed a
      statistically significant decrease in each species with increasing O3 dose.
      Although stomatal conductance declined in parallel with CO2 uptake this did not
      account for the observed decrease in photosynthesis. The decrease in mesophyll
      conductance resulted primarily from a decrease in the apparent carboxylation
      capacity, implying in decreased activity of ribulose 1,5-bisphosphate
      carboxylase/oxygenase. The maximum capacity of carboxylation was consequently
      reduced by over 30% and 50% after 16 h fumigation with 200 and 400 nmol mol(-1)
      O3 respectively. Additionally, in Q. robur, a statistically significant
      inhibition of the CO2 saturated rate of photosynthesis occurred after 16 h with
      400 nmol mol(-1) O3, suggesting that the ability to regenerate ribulose 1,5
      bisphosphate was also impaired. None of the species showed any significant
      decrease in the efficiency of light-limited photosynthesis following fumigation
      at 200 nmol mol(-1) O3, but effects were apparent at 400 nmol mol(-1) O3. The
      common feature in all three species was a decline in carboxylation capacity which
      preceded any other change in the photosynthetic apparatus. 

PMID- 24306635
TI  - Malate regulation of Mg(2+)-ATPase of chloroplast coupling factor 1.
AB  - The regulatory effects of malate on chloroplast Mg(2+)-ATPase were investigated
      and the mechanism was discussed. Malate stimulated methanol-activated membrane
      bound and isolated CF1 Mg(2+)-ATPase activity. The gamma subunit of CF1 may be
      involved in malate regulation of the enzyme function. Modification of gamma
      subunit at one site of the peptide by NEM may affect malate stimulation of ATPase
      while at another site may have no effect. The effect of malate on the Mg(2+)
      ATPase was also controlled by the Mg(2+)/ATP ratio in the reaction medium. The
      enhancing effect of malate on Mg(2+)-ATPase activity depended on the presence of
      high concentrations of Mg(2+) in the reaction mixture. Kinetic study showed that
      malate raised the Vmax of catalysis without affecting the Km for Mg(2+) ATP. The
      experiments imply that the stimulation of Mg(2+)-ATPase by malate is probably
      correlated with the Pi binding site on the enzyme. The regulation of ATPase
      activity by malate in chloroplasts may be relevant to its function in vivo. 

PMID- 24306636
TI  - Reduction of cytochromes with menaquinol and sulfide in membranes from green
      sulfur bacteria.
AB  - Reduction of cytochromes in chlorosome-free membranes of Chlorobia was studied
      anaerobically, with an LED array spectrophotometer. For Chlorobium tepidum these
      membranes contained 0.2 moles cytochrome per mole of bacteriochlorophyll a. The
      observed change upon complete reduction of oxidized membranes with dithionite
      could be satisfactorily fitted with three cytochrome components having absorption
      peaks at 553 (cyt c), 558 and 563 nm (cyt b), in relative amounts of 5:1:2. About
      20% of total cytochrome 553 were reducible by ascorbate. Menaquinol reduced all
      of the 553-component, and this reduction was sensitive to stigmatellin, NQNO and
      antimycin A. The reduction was insensitive to KCN. However, it was transient at
      low concentrations of menaquinol in the absence of KCN, but permanent in its
      presence, demonstrating that electron transport into an oxidation pool was
      blocked. The 563-component was only slightly reduced by menaquinol unless NQNO or
      antimycin were present. The stimulation of cytochrome 563-reduction by these
      inhibitors was more pronounced in the presence of ferricyanide. This phenomenon
      reflects 'oxidant-induced reduction' of cytochrome b and demonstrates that a Q
      cycle is operative in Chlorobia. Also, sulfide fully reduced cytochrome 553, but
      more slowly than menaquinol. KCN inhibited in this case, as did stigmatellin,
      NQNO and antimycin A. NQNO was a better inhibitor than antimycin A. Cytochrome
      563 again was hardly reduced unless antimycin A was added. The effect was more
      difficult to observe with NQNO. This supports the conclusion that sulfide
      oxidation proceeds via the quinone pool and the cytochrome bc-complex in green
      sulfur bacteria. 

PMID- 24306637
TI  - Differential activities of heterocyst ferredoxin, vegetative cell ferredoxin, and
      flavodoxin as electron carriers in nitrogen fixation and photosynthesis in
      Anabaena sp.
AB  - In cyanobacteria an increasing number of low potential electron carriers is
      found, but in most cases their contribution to metabolic pathways remains
      unclear. In this work, we compare recombinant plant-type ferredoxins from
      Anabaena sp. PCC 7120, encoded by the genes petF and fdxH, respectively, and
      flavodoxin from Anabaena sp. PCC 7119 as electron carriers in reconstituted in
      vitro assays with nitrogenase, Photosystem I, ferredoxin-NADP(+) reductase and
      pyruvate-ferredoxin oxidoreductase. In every experimental system only the
      heterocyst ferredoxin catalyzed an efficient electron transfer to nitrogenase
      while vegetative cell ferredoxin and flavodoxin were much less active. This
      implies that flavodoxin is not able to functionally replace heterocyst
      ferredoxin. When PFO-activity in heterocyst extracts was reconstituted under
      anaerobic conditions, both ferredoxins were more efficient than flavodoxin, which
      suggested that this PFO was of the ferredoxin dependent type. Flavodoxin,
      synthesized under iron limiting conditions, replaces PetF very efficiently in the
      electron transport from Photosystem I to NADP(+), using thylakoids from
      vegetative cells. 

PMID- 24306638
TI  - The resolution and biochemical characterization of subcomplexes of the main light
      harvesting chlorophyll a/b-protein complex of Photosystem II (LHC II).
AB  - LHC II isolated from carnation leaves has been solubilized and resolved by a
      newly developed, vertical-bed non-denaturing isoelectric focusing in
      polyacrylamide slab gels to yield three trimeric subcomplexes focusing at pH
      4.52, 4.42 and 4.37 (designated a, b and c, respectively), comprising
      approximately 38%, 24% and 38% of the chlorophyll. The spectroscopic data
      demonstrated a close similarity among LHC II subcomplexes concerning their
      chlorophyll content and organization. The most alkaline and the most acidic
      subcomplex contained the 27 kDa polypeptide of LHC II while the intermediate pI
      fraction contained both LHC II polypeptides, i.e. 27 kDa and 26 kDa ones
      associated at 2:1 stoichiometry. The 27 kDa polypeptide could be resolved by
      denaturing isoelectrofocusing into 10 pI molecular isoforms covering 5.90-4.20 pH
      range. Three of the isoforms were found in the subcomplexes a and b and eight in
      the subcomplex c. The 26 kDa polypeptide comprised the unique pI molecular
      isoform focusing at pH 5.61. 

PMID- 24306639
TI  - Electrochromic absorbance changes in the chlorophyll-c-containing alga
      Pleurochloris meiringensis (Xanthophyceae).
AB  - Flash-induced absorbance changes were measured in the Chl-c-containing alga
      Pleurochloris meiringensis (Xanthophyceae) between 430 and 570 nm. In addition to
      the bands originating from redox changes of cytochromes, three major positive and
      tow negative transient bands were observed both 0.7 and 20 ms after the exciting
      flash. These transient bands peaking at 520, 480 and 451 nm and 497 and 465 nm,
      respectively, could be assigned to an almost homogeneous shift of the absorbance
      bands with maxima at 506, 473 and 444 nm, respectively. The shape of the
      absorbance transients elicited from PS I or PS II was identical, and the two
      photosystems contributed nearly equally to the absorbance changes. Furthermore,
      the decay transients were sensitive to the preillumination of the cells. These
      data strongly suggest that the absorbance transients originate from an
      electrochromic response of carotenoid molecules. The pigment species responsible
      for the 506 nm absorption band, probably heteroxanthin or diatoxanthin,
      transferred excitation energy to both photosystems as shown by the aid of 77 K
      fluorescence excitation spectra. 

PMID- 24306640
TI  - A sensitive, simultaneous analysis of ribulose 1,5-bisphosphate
      carboxylase/oxygenase efficiencies: Graphical determination of the CO2/O 2
      specificity factor.
AB  - A simple approach to determine CO2/O2 specificity factor (tau) of ribulose 1,5
      bisphosphate carboxylase/oxygenase is described. The assay measures the amount of
      CO2 fixation at varying [CO2]/[O2] ratios after complete consumption of ribulose
      1,5-bisphosphate (RuBP). Carbon dioxide fixation catalyzed by the carboxylase was
      monitored by directly measuring the moles of (14)CO2 incorporated into 3
      phosphoglycerate (PGA). This measurement at different [CO2]/[O2] ratios is used
      to determine graphically by several different linear plots the total RuBP
      consumed by the two activities and the CO2/O2 specificity factor. The assay can
      be used to measure the amounts of products of the carboxylase and oxygenase
      reactions and to determine the concentration of the substrate RuBP converted to
      an endpoint amount of PGA and phosphoglycolate. The assay was found to be
      suitable for all [CO2]/[O2] ratios examined, ranging from 14 to 215 micromolar
      CO2 (provided as 1-16 mM NaHCO3) and 614 micromolar O2 provided as 50% O2. The
      procedure described is extremely rapid and sensitive. Specificity factors for
      enzymes of highly divergent tau values are in good agreement with previously
      published data. 

PMID- 24306642
TI  - Health: The wider perspective.

PMID- 24306641
TI  - We remember Eugene : (Rabinowitch and his laboratory, during the fifties).
AB  - This article is written in memory of Eugene Rabinowitch, one of the major
      prophets of photosynthesis. I speak on behalf of all the students and post
      doctorial associates who were fortunate to be associated with and to have loved
      this wonderful man. I shall also describe my research with Eugene. We all
      remember him on the 1995 anniversary of his death (May 15, 1973). 

PMID- 24306643
TI  - Love and the addicted physician.
AB  - This paper reviews the cases of two addicted physicians. One is dead and the
      other alive and well as a result of the heroic and compassionate effort of his
      friends. We offer speculations regarding the physicians' special vulnerabilities
      and the role of a tough love in transcending these vulnerabilities. 

PMID- 24306644
TI  - Spiritual support in life threatening illness.
AB  - This work evaluated the experiences of 45 patients of children with cancer and
      101 cancer patients with their home pastors and hospital chaplains. The
      sttisfactions and difficulties enountered in these interactions are detailed, and
      recommendations are offered to aid persons in acute distress. Individuals in
      these circumstances appear to desire spiritual support more than evident
      psychologial aid, though the skillful use of the latter to understant the
      religious desires of the patients and parents is appreciated. It is also evident
      that pastors dealing which problems related to potential terminality are
      themselves under considerble stress. 

PMID- 24306645
TI  - The art of healing and the many worlds of time.
AB  - This essay is a contribution to the understanding of the difficulties involved in
      integrating biomedicine and holistic medicine. The phenomenology of the
      perception of time as described by Mann, Siegler, and Osmond is postulated as
      underlying the different orientations to the practice of medicine. 

PMID- 24306646
TI  - Recent studies of near-death experiences.
AB  - This article consists of a summary of the central points in the work of recent
      investigators of near-death experiences (NDEs). It considers the work of Moody,
      Osis, Rawlings, Ring, Sabom, and Grof as well as the criticisms of Noyes and
      Siegel. The appearance of a common core in the experiences suggests the presence
      of more than ordinary hallucinations. However, NDEs seem to be not literal
      experiences of life beyond death but archetypal experiences, the judgment of the
      validity of which will depend on one's assessment of depth symbolism. 

PMID- 24306647
TI  - Personality, faith, development, and work attitudes.
AB  - Drawing upon the developmental work of Loevinger and Fowler, the author
      speculates upon the existence of work attitudes that accompany each stage and
      explains how the attitudes influence people's orientations toward work and
      family. 

PMID- 24306648
TI  - Masochism and piety.
AB  - A recent tract,The Whipping, is parallel in many ways to both Victorian
      flagellation pornography and medieval flagellation penance movements. The
      spirituality ofThe Whipping is seen to be basically masochistic. The same trend
      is easily seen inmuch standard pietistic literature. The question is raised
      whether the spiritual masochism does not represent a repressed and sublimated
      sexual masochism. If so, then Christians should ask themselves if they can
      consistently condemm sexual masochism while advocating its spritual counterpart,
      or vice versa. 

PMID- 24306649
TI  - Isolation and characterisation of cDNA clones for tomato polygalacturonase and
      other ripening-related proteins.
AB  - Gene expression during the ripening of tomato fruit was investigated by cDNA
      cloning and hybrid-select translation. A cDNA library was prepared from poly(A)
      containing mRNA from ripe tomato fruit and sreened by differential hybridization.
      146 ripening-related cDNA clones were found. Eleven groups and eight unique
      clones have been identified so far. The sizes of the cloned cDNA inserts were
      determined and type-members for seven groups were used in hybrid selection
      experiments. Six of the seven clones encode translation products corresponding to
      six ripening related polypeptides detected previously by in vitro translation of
      total cytoplasmic RNA (14). One cDNA group codes for a Mr 48 000 protein that was
      identified as polygalacturonase on the basis of immunoprecipitation with specific
      antiserum raised against tomato polygalacturonase. re]19840918 rv]19850613
      ac]19850618. 

PMID- 24306650
TI  - Simple binary vectors for DNA transfer to plant cells.
AB  - Cosmid binary vectors for the introduction of DNA into plant cells have been
      constructed. These vectors are derived from the replicon of the broad host range
      plasmid pRK2 and contain the T-DNA border regions between which have been placed
      a chimaeric gene conferring resistance to kanamycin in plant cells. Appropriate
      restriction endonuclease targets have also been placed between the border
      regions. These binary vectors, in conjunction with appropriate Agrobacterium
      strains, are capable of delivering DNA to plant cells in cocultivation
      experiments with very high efficiency. The transformation frequency is shown to
      be somewhat dependent on the replicon used. re]19850121 rv]19850506 ac]19850513. 

PMID- 24306651
TI  - Cytokinins modulate the expression of genes encoding the protein of the light
      harvesting chlorophyll a/b complex.
AB  - Tobacco cell suspension cultures responded to cytokinins (for instance kinetin)
      by full chloroplast differentiation. The hormone had the effect of stimulating
      the appearance of a few prominent plastid proteins. Synthesis of the light
      harvesting chlorophyl a/b-binding protein (LHCP) in response to kinetin was
      noteworthy (Axelos M. et al.: Plant Sci Lett 33:201-212, 1984).Poly(A)(+)RNAs
      were prepared from cells grown in the presence of or without added kinetin.
      Poly(A)(+)RNA recovery and translation activity were not quantitatively altered
      by the hormone treatment. In vitro translation of polyadenylated mRNA into
      precursor polypeptides of LHCP (pLHCP) was quantified by immunoprecipitation and
      SDS-PAGE fractionation of pLHCP immunoprecipitates: pLHCP-mRNA translating
      activity was found to be stimulated in parallel to mature LHCP accumulation by
      kinetin-induced cells.Dot-blot and northern-blot hybridizations of poly(A)(+)RNA
      were carried out, using as a probe a pea LHCP-cDNA clone (Broglie R. et al.: Proc
      Natl Acad Sci USA 78: 7304-7308, 1981). A ten-fold increase of the level of pLHCP
      encoding sequences was observed in poly(A)(+)RNA prepared from 9-d kinetin
      stimulated cells, compared to control cells. Oligo(dT)-cellulose-excluded RNA
      fractions exhibited very low hybridization levels, in the same ratios as those
      obtained with poly(A)(+)RNA.Thus, the expression of LHCP-gene activity, in
      response to kinetin addition to tobacco cell suspension cultures, is regulated by
      the level of pLHCP-encoding mRNA rather than by translational or post
      translational controls. re]19850218 rv]19850605 ac]19850613. 

PMID- 24306652
TI  - Developmental expression of sunflower 11S storage protein genes.
AB  - Helianthinin is the major globulin storage protein of sunflower seeds. Antiserum
      prepared against purified helianthinin was used to study storage protein
      accumulation in developing sunflower embryos. Synthesis of helianthinin begins
      within 7 days after anthesis (DAA) and it accumulates rapidly until 19 DAA.
      Storage protein synthesis then slows until seed maturation at 30 DAA. Anti
      helianthinin was also used to select specific cDNA recombinants from a
      bacteriophage lambda gt11 cDNA expression library prepared from immature
      sunflower embryo polyadenylated RNA. One of these recombinants, lambda gt11H3,
      contained a 300 bp cDNA insert which was used as a hybridization probe for RNA
      gel blot and RNA dot blot analyses. This probe hybridizes with an approximately
      1.9 kb sunflower embryo transcript. Helianthinin mRNA is present in embryos 7 DAA
      and accumulates to maximum prevalence at 12 DAA which corresponds to the period
      of maximum helianthinin accumulation. Soon after 12 DAA helianthinin RNA begins
      to decrease. Full length helianthinin mRNA is not detectable in mature seeds or
      in germinated seedlings. These results indicate that synthesis of the 11S
      sunflower seed storage protein occurs during a specific stage of embryogenesis
      and is regulated by the accumulation of helianthinin mRNA. 

PMID- 24306653
TI  - Red light inhibits blue light-induced chloroplast development in cultured plant
      cells at the mRNA level.
AB  - During the blue light-dependent chloroplast differentiation in suspension
      cultured cells of tobacco (Nicotiana tabacum var. 'Samsun') chlorophylls and
      other pigments as well as specific membrane and stroma proteins are synthesized
      de-novo: the 32-kD membrane protein of photosystem II, the small subunit (SSU)
      and the large subunit (LSU) of ribulose-bisphosphate carboxylase/oxygenase (EC.
      4.1.1.39; RuBPCase). Parallel with their accumulation the steady-state
      concentration of the corresponding mRNAs increases rapidly and coordinately as
      was detected by employing cloned DNA sequences complementary to these plastid and
      nuclear transcripts as hybridization probes. The blue light-induced change in the
      concentration of the mRNAs analyzed here is abolished by red light when applied
      to cells at an early or late stage of chloroplast differentiation. The results
      indicate that blue light exerts a positive and coordinate influence on both
      genomes, nuclear and plastid, in chloroplast development of tobacco cells.
      re]19850308 rv]19850605 ac]19850627. 

PMID- 24306654
TI  - A microassay for detection of DNA and RNA in small numbers of plant cells.
AB  - A microtechnique for the detection of DNA or RNA in small numbers of plant cells
      (1-50) has been developed using cauliflower mosaic virus (CaMV) infection of
      turnip as a model system. Both DNA and RNA extracted from 10 mesophyll
      protoplasts from CaMV-infected plants can be detected by hybridization using a
      radioactive probe made from cloned CaMV DNA (pCaMV10). No hybridization above
      background was detected in extracts of protoplasts from uninfected plants. At
      least 0.15 pg (11 000 molecules) of purified pCaMV10 DNA can be detected. This
      method is superior to existing 'macro' techniques for nucleic acid detection as
      smaller amounts of tissue are required and the detection is approximately 100
      fold more sensitive. re]19850326 rv]19850530 ac]19850611. 

PMID- 24306655
TI  - Nucleotide sequence of a cDNA clone of Brassica napus 12S storage protein shows
      homology with legumin from Pisum sativum.
AB  - The most abundant protein in seeds of Brassica napus (L.) is cruciferin, a
      legumin-like 12S storage protein. By in vitro translation of embryo RNA, and
      pulse-chase labelling of cultured embryos with (14)C-leucine, we have shown that
      the 30 kd alpha polypeptides and 20 kd beta polypeptides of cruciferin are
      synthesized as a family of 50 kd precursors which are cleaved post
      translationally. One member of the cruciferin family was cloned from embryo cDNA
      and sequenced. The nucleotide sequence of the cruciferin cDNA clone, pC1,
      contains one long open reading frame, which originates in a hydrophobic signal
      peptide region. Therefore, the complete sequence of the cruciferin mRNA was
      obtained by primer extension of the cDNA. The predicted precursor polypeptide is
      488 amino acids long, including the 22 amino acids of the putative signal
      sequence. The amino acid composition of cruciferin protein is very similar to the
      predicted composition of the precursor. Comparison with an amino acid sequence of
      legumin from peas, deduced from the nucleotide sequence of a genomic clone, shows
      that the alpha polypeptide precedes the beta polypeptide on the precursor.
      Cruciferin and legumin share 40% homology in the regions which can be aligned.
      However, cruciferin contains a 38 amino acid region high in glutamine and glycine
      in the middle of the alpha subunit, which is absent in legumin. Legumin has a
      highly charged region, 57 amino acids long, at the carboxyl-end of the alpha
      subunit, which is not found in cruciferin. Both of these regions appear to have
      originated by reiteration of sequences. re]19850513 ac]19850715. 

PMID- 24306656
TI  - Dual-task performance in young and older adults: speed-accuracy tradeoffs in
      choice responding while treadmill walking.
AB  - Thirty-one young (mean age = 20.8 years) and 30 older (mean age = 71.5 years) men
      and women categorized as physically active (n = 30) or inactive (n = 31)
      performed an executive processing task while standing, treadmill walking at a
      preferred pace, and treadmill walking at a faster pace. Dual-task interference
      was predicted to negatively impact older adults' cognitive flexibility as
      measured by an auditory switch task more than younger adults; further,
      participants' level of physical activity was predicted to mitigate the relation.
      For older adults, treadmill walking was accompanied by significantly more rapid
      response times and reductions in local- and mixed-switch costs. A speed-accuracy
      tradeoff was observed in which response errors increased linearly as walking
      speed increased, suggesting that locomotion under dual-task conditions degrades
      the quality of older adults' cognitive flexibility. Participants' level of
      physical activity did not influence cognitive test performance. 

PMID- 24306658
TI  - CD151 overexpression is associated with poor prognosis in patients with pT3
      gastric cancer.
AB  - INTRODUCTION: CD151, a transmembrane protein of the tetraspanin family, is
      implicated in the regulation of cell-substrate adhesion and cell migration.
      Overexpression of CD151 has been reported in several cancers and controls MET
      dependent neoplastic growth by enhancing receptor signaling. However, association
      of CD151 overexpression with MET or tumor progression has not been reported in
      gastric cancer. MATERIALS AND METHODS: We conducted immunohistochemical analysis
      of CD151 overexpression in 491 pT3 gastric carcinomas and analyzed the
      relationship with MET overexpression and prognostic significance. RESULTS: CD151
      was highly expressed in 119 gastric carcinomas (24.2 %) and was significantly
      associated with higher pN stages. Patients with CD151-positive gastric cancer
      showed shorter overall (p = 0.003) and disease-free survival (p = 0.001) compared
      with patients with CD151-negative gastric carcinoma. CD151 overexpression was an
      independent prognostic factor for overall survival [hazard ration (HR) 1.335; 95
      % CI 1.005-1.775; p = 0.046] and disease-free survival (HR 1.903; 95 % CI 1.348
      2.685; p < 0.001). Co-overexpression of CD151 and MET was observed in 30 (6.1 %)
      gastric cancers and was more frequent in advanced pN stages than in other groups.
      Moreover, co-overexpression of CD151 and MET was a strong independent prognostic
      factor for overall survival (HR 3.163; 95 % CI 1.958-5.108; p < 0.001) and
      disease-free survival (HR 3.834; 95 % CI 2.145-6.852; p < 0.001). CONCLUSION:
      CD151 overexpression is an independent prognostic factor and could be a potential
      molecular therapeutic target in patients with advanced gastric cancers. Further
      studies are needed to establish the biological significance of CD151/MET co
      overexpression and the potential of targeting both molecules as a therapeutic
      strategy.

PMID- 24306659
TI  - Utilization of radiotherapy for malignant phyllodes tumors: analysis of the
      National Cancer Data Base, 1998-2009.
AB  - BACKGROUND: Malignant phyllodes tumors of the breast have traditionally been
      treated with surgical excision. Recently, the use of adjuvant radiotherapy has
      been advocated to reduce the risk of local recurrence; however, this
      recommendation is controversial in the absence of consistent outcome data. We
      hypothesize that there has been a trend toward increased utilization of adjuvant
      radiotherapy for malignant phyllodes tumors despite its uncertain effect on
      outcomes. METHODS: Using the National Cancer Data Base, predictors of
      radiotherapy utilization were examined for women with malignant phyllodes from
      1998 to 2009. Kaplan-Meier and Cox regression models were generated to determine
      the effect of radiotherapy on local recurrence (LR), disease-free survival (DFS),
      and overall survival (OS). RESULTS: Of the 3,120 patients with malignant
      phyllodes, 57 % underwent breast conservation surgery and 42 % underwent
      mastectomy. Overall, 14.3 % of women received adjuvant radiotherapy. Utilization
      of radiotherapy doubled over the study period (9.5 % in 1998-1999 vs. 19.5 % in
      2008-2009, p < 0.001). Women were significantly more likely to receive
      radiotherapy if they were diagnosed later in the study, were age 50-59 years old,
      had tumors >10 cm, or had lymph nodes removed. For the 1,774 patients with
      available recurrence data, overall recurrence was 14.1 %, and LR was 5.9 %. In
      adjusted models, adjuvant radiotherapy reduced LR (aHR 0.43, 95 % CI 0.19-0.95)
      but did not impact DFS or OS after 53 months' median follow-up. CONCLUSIONS:
      Utilization of adjuvant radiotherapy for malignant phyllodes doubled from 1998 to
      2009. Radiotherapy significantly reduced LR but had no effect on DFS or OS.

PMID- 24306660
TI  - The prognostic significance of an R1 resection in gastric cancer patients treated
      with adjuvant chemoradiotherapy.
AB  - BACKGROUND: A microscopically irradical (R1) resection is a well-known adverse
      prognostic factor after gastric cancer surgery. However, the prognostic
      significance of an R1 resection in gastric cancer patients who are treated with
      chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore,
      the aim of this study was to evaluate the effect of an R1 resection on
      (recurrence-free) survival in gastric cancer patients who were treated with CRT
      after surgery. METHODS: Gastric cancer patients who had undergone a resection
      with curative intent followed by adjuvant CRT at our institute between 2001 and
      2011 were included. CRT consisted of radiotherapy (45 Gy/25 fractions) combined
      with concurrent capecitabine (with or without cisplatin) or 5
      fluorouracil/leucovorin. RESULTS: A consecutive series of 110 patients was
      studied, including 80 (73 %) patients who had undergone an R0 resection and 30
      (27 %) patients with an R1 resection. Pathologic T-classification (p = 0.26), N
      classification (p = 0.77), and histologic subtype according to Lauren (p = 0.071)
      were not significantly different between these groups. Three-year recurrence-free
      survival (45 vs. 35 %, p = 0.34) and overall survival (47 vs. 48 %, p = 0.58) did
      not significantly differ between patients who had undergone an R0 or R1
      resection. In a multivariate analysis, pathologic T-classification and N
      classification were independent prognostic factors for survival. CONCLUSIONS: A
      R1 resection was not an adverse prognostic factor in gastric cancer patients who
      had undergone CRT after the operation.

PMID- 24306661
TI  - Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM).
AB  - PURPOSE: To investigate the diagnostic and prognostic value of circulating tumor
      cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural
      mesothelioma (MPM). METHODS: We prospectively evaluated CTCs in 7.5 mL of
      peripheral blood sampled from patients with a suspicion of MPM. A semiautomated
      system was used to capture CTCs with an antibody against the epithelial cell
      adhesion molecule. RESULTS: Of 136 eligible patients, 32 were finally diagnosed
      with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 %
      (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P =
      0.011). The CTC count was significantly higher in MPM patients than in NM
      patients (P = 0.007), and a receiver operating characteristic (ROC) curve
      analysis showed an insufficient capability of the CTC test in discrimination
      between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence
      interval, 0.523-0.723; P = 0.036). Among MPM patients, CTCs were more frequently
      detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those
      with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC
      count >= 1) were a significant factor to predict a poor prognosis among
      epithelioid patients (median overall survival, 22.3 months for positive CTCs vs.
      12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P =
      0.649). A multivariate analysis showed that positive CTCs were a significant and
      independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 %
      confidence interval, 1.530-5.511; P = 0.001) for epithelioid MPM patients.
      CONCLUSIONS: CTC was a promising marker in diagnosis and prediction of prognosis
      in MPM, especially in epithelioid MPM.

PMID- 24306662
TI  - DNA methylation profiling identifies EYA4 gene as a prognostic molecular marker
      in hepatocellular carcinoma.
AB  - BACKGROUND: DNA hypermethylation plays important roles in carcinogenesis by
      silencing key genes. This study aims to identify pivotal genes in hepatocellular
      carcinoma (HCC) by DNA methylation microarray and to assess their prognostic
      values. MATERIALS AND METHODS: DNA methylation microarray was performed in 45
      pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to
      identify hypermethylated genes in HCC. Potential prognosis-related genes were
      selected among hypermethylated genes by analyzing influences of methylation
      levels on disease-free survival (DFS) and overall survival (OS) in 45 patients.
      Their prognostic values were validated in 154 patients with HCC (including the
      initial 45 patients) to determine the independent prognostic gene. RESULTS:
      Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with
      liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely
      associated with DFS (both P < 0.050), and methylation levels of EYA4 were
      inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely
      related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size
      were independent predictors of both shorter DFS and OS, and higher Barcelona
      Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS
      (all P < 0.050). CONCLUSIONS: EYA4 functions as a prognostic molecular marker in
      HCC. Its aberrant hypermethylation and subsequent down-regulation may promote
      tumor progression.

PMID- 24306663
TI  - Parathyroid surgery in the elderly: should minimally invasive surgery be
      abandoned?
AB  - BACKGROUND: Single adenoma is the cause of 80 % of primary hyperparathyroidism
      (PHPT) resulting in wide acceptance of minimally invasive parathyroidectomy
      (MIP). The incidence of PHPT increases with age. Little information is available
      regarding the prevalence of multiglandular disease (MGD) in older patients.
      METHODS: The records of 537 patients that underwent parathyroid surgery between
      January 2005 and October 2012 at two endocrine surgery referral centers were
      retrospectively reviewed. Comparison was performed between patients younger than
      65 and older than 65 years of age. Clinical variables included preoperative
      laboratories and imaging, extent of neck exploration, number of glands excised,
      and intraoperative parathyroid hormone levels during surgery. RESULTS: There were
      374 (70 %) patients in the younger age group (YG) and 163 (30 %) patients in the
      older age group (OG). The mean age was 50 +/- 0.5 and 71 +/- 0.4 years,
      respectively. There was no difference between the groups in terms of gender or
      laboratory results. MGD was significantly more common in the OG (24 % vs. 12 %; p
      = 0.001) and similarly MIP was less commonly completed in the OG (49 % vs. 68 %;
      p < 0.001). Cure rates were comparable between the OG and YG (93 % vs. 95 %; p =
      0.27). In the OG, patients with MGD had significantly smaller glands as compared
      to patients with single adenomas in this group (331 +/- 67 vs. 920 +/- 97 mg; p =
      0.006, respectively). CONCLUSIONS: MGD in PHPT was found to be more prevalent in
      older patients. Planning a bilateral neck exploration should be considered in
      older patients, especially when a relatively small gland is suggested by imaging
      or encountered during surgery.

PMID- 24306664
TI  - Is atypical metastasis obstructive to sentinel node navigation surgery in early
      gastric cancer patients?

PMID- 24306665
TI  - Computed tomography (CT) venography using a multidetector CT prior to the
      percutaneous external jugular vein approach for an implantable venous-access
      port.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to determine the success
      rate and complications of using the percutaneous approach of the external jugular
      vein (EJV) for placement of a totally implantable venous-access port (TIVAP) with
      a preoperative estimate of the detailed anatomical orientation of the cervical
      venous plexus using computed tomography venography (CT-V). METHODS: A prospective
      cohort study of 45 patients in whom placement of a TIVAP was attempted via the
      right EJV was conducted. The preoperative anatomical estimation of the cervical
      venous plexus was performed with CT-V using a Multidetector Helical 16-section
      CT. The angulation between the right EJV and the right subclavian vein, anterior
      jugular vein, transverse cervical vein, and suprascapular vein was estimated.
      RESULTS: CT-V success was achieved in 45 of 45 patients (100 %). A plexus of
      veins under the clavicle was most commonly responsible for the insertion of the
      central venous catheter. The EJV approach resulted in a successful cannulation
      rate of 93 %. No initial complications of pneumothorax or carotid artery puncture
      occurred during insertion procedures. Late complications occurred in three
      patients. These included one port erosion (2 %), one catheter occlusion (2 %),
      and one wound hematoma (2 %). Catheter-related infections were observed in one
      patient (2 %). CONCLUSIONS: The percutaneous EJV approach with CT-V guidance is
      an optional method for patients with multiple central venous cannulations, those
      in hemodialysis, or those with long catheter indwelling periods.

PMID- 24306666
TI  - A body shape index has a good correlation with postoperative complications in
      gastric cancer surgery.
AB  - BACKGROUND: The relationship between obesity and surgical complications has been
      controversial. A Body Shape Index (ABSI) is a newly developed anthropometric
      index based on waist circumference adjusted for height and weight. The aim of
      this study was to investigate the relationship between ABSI and surgical
      complications. METHODS: From November 2001 to September 2012, 4,813 patients
      underwent curative resection for gastric cancer. ABSI was defined as waist
      circumference divided by (BMI(2/3)height(1/2)). Data of clinicopathologic
      characteristics and morbidity were collected by retrospective review. Binary
      logistic regression was used for multivariable analyses to determine whether ABSI
      was independently associated with postoperative complications. RESULTS: The
      incidence of overall surgical complications was 13.4 %, and the most common
      complication was ileus (2.8 %). In the multivariable analysis, ABSI was an
      independent factor for overall complications [odds ratio (OR), 1.22; 95 %
      confidence interval (CI) 1.01-1.48; P = 0.041). However, BMI showed no
      statistical significance (OR, 1.03; 95 % CI 1.00-1.06; P = 0.063). In the
      subgroup analyses, ABSI was significantly associated with overall complications
      regarding open gastrectomy (OR, 1.26; 95 % CI 1.01-1.57; P = 0.039). Regarding
      laparoscopy-assisted gastrectomy, ABSI had no significant effect on overall
      complications (P = 0.844). CONCLUSIONS: ABSI shows good correlation with surgical
      complications in patients with gastric cancer. Further studies are needed for the
      various clinical roles of ABSI, and the results could be helpful to determine the
      effect of abdominal obesity on gastric cancer surgery and the clinical usefulness
      of ABSI.

PMID- 24306667
TI  - Analysis of bevacizumab-based preoperative radiochemotherapy in patients with
      locally advanced rectal cancer on surgery-associated spectrum of complications.
AB  - BACKGROUND: Preoperative radiochemotherapy (RCT) is a standard of care for
      patients with locally advanced rectal cancer (LARC; stages II and III). Results
      of our phase II study (BevXelOx-RT) have shown that this regimen is feasible but
      without a significant improvement of pathological complete response. Whether
      preoperatively administered bevacizumab, due to its specific toxicity profile,
      leads to increased rates of surgical complications is currently a subject for
      debate. This analysis focusses on the surgery-associated spectrum of
      complications. METHODS: Data from 62 patients with rectal cancer (uT3-4; N0/1,
      M0) of the phase II trial were analyzed. Patients received radiotherapy (50.4/1.8
      Gy fractions), simultaneous bevacizumab 5 mg/kg (d1, d15, d29), and capecitabine
      825 mg/m(2) twice daily (d1-14, d22-35), oxaliplatin 50 mg/m(2) (d1, d8, d22,
      d29). Four to six weeks after RCT, surgical resection was performed. RESULTS:
      Overall, 69/69 patients underwent surgery, and 66 (95.7 %) patients had R0
      resection. Surgery was mainly conducted (in 66 %) by highly experienced surgeons
      (>20 resections of rectal cancer/year) with differences between the institutions
      due to the operative procedures but without effects on the rate of R0 resection
      or complications. The average duration of surgery was 239 min (+/-10). Frequency
      of multivisceral resections (11 %), intraoperative (8 %) and postoperative (43 %)
      complications were all in the expected range. In particular, we did not observe
      an increased rate of postoperative bleedings (3 %). The postoperative mortality
      rate was 0 %. CONCLUSIONS: Quantity and the kind of surgery-associated spectrum
      of complications followed by a preoperative bevacizumab-containing RCT regimen in
      patients with LARC were in line with comparable trials of bevacizumab-based
      approaches.

PMID- 24306668
TI  - Elevated preoperative systemic inflammatory markers predict poor outcome in
      localized soft tissue sarcoma.
AB  - BACKGROUND: Systemic inflammation has been implicated in cancer development and
      progression. This study sought to determine whether systemic inflammatory markers
      can predict postoperative outcome in soft tissue sarcoma (STS). METHODS: A total
      of 162 cases of primary, localized STS were reviewed. Patients with evidence of
      infectious or inflammatory diseases were excluded. The mean follow-up period was
      46.7 months. The level of serum C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR) measured
      before surgery were evaluated for association with disease-specific survival and
      local recurrence. RESULTS: The mean values of CRP, ESR, and NLR were 0.79 mg/dL,
      18.8 mm/h, and 2.12, respectively. Cutoff values derived from receiver-operating
      characteristic curve analysis were 0.20 mg/dL for CRP, 10.0 mm/h for ESR, and
      2.50 for NLR. On univariate analysis, all inflammatory markers were associated
      with disease-specific survival (CRP: P = 0.007; ESR: P = 0.022; NLR: P = 0.030).
      On multivariate analysis, the CRP level (P = 0.019) and ESR (P = 0.013) remained
      significant. Elevation of multiple markers was a more significant prognostic
      factor than elevation of a single marker (P = 0.001). However, none of the
      inflammatory markers was associated with local recurrence (CRP: P = 0.345; ESR: P
      = 0.271; NLR: P = 0.570). Histologic grade was strongly correlated with
      inflammatory marker values (NLR: P < 0.001; ESR: P = 0.002; CRP: P = 0.007).
      CONCLUSIONS: Preoperative systemic inflammatory status, assessed by using
      multiple serum markers, predicted disease-specific survival in STS.

PMID- 24306670
TI  - Demonstration of an odorous intramale primer effect in short-tailed vole,Microtus
      agrestis L.
AB  - Anal (proctodeal) glands of maleMicrotus agrestis housed in social isolation
      undergo severe atrophy. Their weight and volume is significantly lower than those
      of the stock control males. The atrophied glands can be revived by subjecting
      deprived voles to various social odors. Atrophied glands of isolated males do not
      respond to the odors of male and female urine, voided feces of females, and
      unvoided feces of males. Atrophied anal glands of males exposed to voided male
      feces (which have passed the orifice of the anal gland) and soiled bedding from
      adult males show strong recrudescence. The mean weight and volume of the glands
      and plasma testosterone level are significantly higher than of males maintained
      in complete social isolation, although they are significantly less than those of
      stock control males. Atrophied glands of socially deprived males strongly respond
      to the odor of ethereal extract of gland secretion. In males exposed daily to
      anal gland secretion extract, the weight and volume of the gland and plasma
      testosterone level increase and are not significantly different from those of
      stock controls. They enjoy higher plasma testosterone levels and consequently
      larger and more active anal glands than complete isolates. 

PMID- 24306671
TI  - Sabulodes caberata guenee (Lepidoptera: Geometridae) : Components of its sex
      pheromone gland.
AB  - A 6,9-nonadecadiene, (Z)-9-nonadecene, andn-nonadecane were identified in
      extracts of sex pheromone glands of femaleSabulodes caberata Guenee. Potential
      pheromonal activity of gland components was assessed by electroantennogram
      measurements of gas-chromatographic fractions of abdominal tip extracts. Chemical
      identification was based on gas chromatography and mass spectrometry of parent
      compounds, hydrogenation products, ozonolysis products, dimethyl disulfide
      adducts, and synthesis. The monoene was synthesized via coupling of alkyl and
      acetylenic intermediates. (Z,Z)-6,9-Nonadecadiene (Z6,Z9-19?H) was synthesized
      from methyl linoleate via chain lengthening. SyntheticZ6,Z9-19?H had the same
      retention times on polar and nonpolar capillary gas-chromatographic columns as
      the 6,9-nonadecadiene from the sex pheromone glands. In field testsZ6,Z9-19:H
      alone produced trap catch of maleS. caberata and addition of (Z)-9-nonadecene orn
      nonadecane had no effect on trap catch. 

PMID- 24306672
TI  - Pinosylvin and pinosylvin methyl ether as feeding deterrents in green alder.
AB  - Snowshoe hare (Lepus americanus) feeding preferences for Alaskan green alder
      (Alnus crispa) are governed by the concentrations of two deterrent secondary
      metabolites, pinosylvin and pinosylvin methyl ether. For instance, the preference
      of mature internodes over juvenile internodes was correlated with about a
      threefold increase in the levels of these compounds in the juvenile form. During
      the last year of the study, however, the levels of these compounds dropped below
      the threshold of avoidance in both types of internodes, resulting in
      nondiscriminatory use by hares even though the relative levels of these
      metabolites remained the same between the juvenile and mature form internodes.
      These conclusions are strongly supported with feeding bioassays using pure
      pinosylvin, pinosylvin methyl ether, and other less active secondary metabolites
      found in alder. 

PMID- 24306673
TI  - Prediction of release ratios of multicomponent pheromones from rubber septa.
AB  - A method has been developed to predict the release ratio of the components of
      blends of alcohols, acetates, and/or aldehydes from rubber septa. The
      calculations of predicted release ratios are based on the relative vapor
      pressures of the components. The relative vapor pressures of the compounds were
      calculated from their retention indices on a liquid crystal capillary gas
      chromatographie column. The correlation between the theoretically predicted and
      experimentally determined ratios was very good. Thus, formulations can be
      prepared that will release a desired ratio of the components of a multicomponent
      pheromone blend. 

PMID- 24306674
TI  - Characterisation of crystalline-amorphous blends of sucrose with terahertz-pulsed
      spectroscopy: the development of a prediction technique for estimating the degree
      of crystallinity with partial least squares regression.
AB  - The control of the amorphous and crystalline states of drugs and excipients is
      important in many instances of product formulation, manufacture, and packaging,
      such as the formulation of certain (freeze-dried) fast melt tablets. This study
      examines the use of terahertz-pulsed spectroscopy (TPS) coupled with two
      different data analytical methods as an off-line tool (in the first instance) for
      assessing the degree of crystallinity in a binary mixture of amorphous and
      polycrystalline sucrose. The terahertz spectrum of sucrose was recorded in the
      wave number range between 3 and 100 cm(-1) for both the pure crystalline form and
      for a mixture of the crystalline and amorphous (freeze-dried) form. The THz
      spectra of crystalline sucrose showed distinct absorption bands at ~48, ~55, and
      ~60 cm(-1) while all these features were absent in the amorphous sucrose.
      Calibration models were constructed based on (1) peak area analysis and (2)
      partial least square regression analysis, with the latter giving the best LOD and
      LOQ of 0.76% and 2.3%, respectively. The potential for using THz spectroscopy, as
      a quantitative in-line tool for percent crystallinity in a range of complex
      systems such as conventional tablets and freeze-dried formulations, is suggested
      in this study. 

PMID- 24306675
TI  - Factors affecting the use of impedance spectroscopy in the characterisation of
      the freezing stage of the lyophilisation process: the impact of liquid fill
      height in relation to electrode geometry.
AB  - This study aims to investigate the application of impedance spectroscopy using
      fixed electrode geometries on a standard glass vial in the characterisation of
      the freezing process of solutions at different fill liquid volumes. Impedance
      spectra (between 10 and 10(6) Hz) were recorded every 3 min, during the freezing
      cycle on a solution of 30 mg/mL sucrose contained within 10 mL glass vials having
      an electrode system (two thin copper foils: w, 18 mm; h, 5 mm) affixed to the
      external surface of the vial. A fill factor (Phi) was defined in terms of the
      relative height of the solution volume to the height of the electrodes from the
      base of the vial. Solution volumes of 1.5 to 5 mL (corresponding to Phi= 0.5-1.6)
      were investigated to establish the applicability of having a fixed electrode
      geometry for a range of solution volumes. A linear relationship between the time
      duration of the ice formation/solidification phase and the fill factor suggests
      that fixed electrode geometries may be used to investigate a range of fill
      volumes. The benefit of this approach is that it does not invade the solution and
      hence records the freezing process without providing additional nucleation sites
      and in a manner which is representative of the entire fill volume. 

PMID- 24306676
TI  - A case study of in silico modelling of ciprofloxacin hydrochloride/metallic
      compound interactions.
AB  - With the development of physiologically based absorption models, there is an
      increased scientific and regulatory interest in in silico modelling and
      simulation of drug-drug and drug-food interactions. Clinically significant
      interactions between ciprofloxacin and metallic compounds are widely documented.
      In the current study, a previously developed ciprofloxacin-specific in silico
      absorption model was employed in order to simulate ciprofloxacin/metallic
      compound interaction observed in vivo. Commercially available software
      GastroPlusTM (Simulations Plus Inc., USA) based on the ACAT model was used for
      gastrointestinal (GI) simulations. The required input parameters, relating to
      ciprofloxacin hydrochloride physicochemical and pharmacokinetic characteristics,
      were experimentally determined, taken from the literature or estimated by
      GastroPlusTM. Parameter sensitivity analysis (PSA) was used to assess the
      importance of selected input parameters (solubility, permeability, stomach and
      small intestine transit time) in predicting percent drug absorbed. PSA identified
      solubility and permeability as critical parameters affecting the rate and extent
      of ciprofloxacin absorption. Using the selected input parameters, it was possible
      to generate a ciprofloxacin absorption model, without/with metal cation
      containing preparations co-administration, which matched well the in vivo data
      available. It was found that reduced ciprofloxacin absorption in the presence of
      aluminium hydroxide, calcium carbonate or multivitamins/zinc was accounted for by
      reduced drug solubility. The impact of solubility-permeability interplay on
      ciprofloxacin absorption can be observed in the ciprofloxacin-aluminium
      interaction, while in ciprofloxacin-calcium and ciprofloxacin-zinc interactions,
      effect of solubility was more pronounced. The results obtained indicate that in
      silico model developed can be successfully used to complement relevant in vitro
      studies in the simulation of physicochemical ciprofloxacin/metallic compound
      interactions. 

PMID- 24306677
TI  - Evaluation of citrus fibers as a tablet excipient.
AB  - The consumption of fibers is associated with many health benefits, such as a
      reduction of cardiovascular and gastrointestinal diseases, control of body
      weight, and prevention of diabetes. Despite the widespread use of fiber
      supplements such as capsules or tablets, there is an almost complete lack of
      information concerning the technological properties of functional fibers used in
      nutraceutical formulations. The aim of this work was to characterize the
      technological properties of citrus fibers necessary for their use as a processing
      aid in tableting. The results obtained showed that citrus fibers share many
      properties of other polysaccharides used as tableting excipients, such as thermal
      behavior and compaction mechanism, together with an appreciable tabletability.
      However, the most interesting properties resulted from their disintegration
      power. Citrus fibers behaved in a similar manner to the well-known super
      disintegrant croscarmellose sodium and resulted to be little susceptible to their
      concentration, to lubricant type, and lubricant concentration. Thus, this work
      supports the idea of a potential use of citrus fibers as "active" substances and
      processing aid in the tableting of nutraceutical products and also as functional
      excipient in pharmaceutical tablets formulation. 

PMID- 24306678
TI  - Oral lichen planus may enhance the expression of Th17-associated cytokines in
      local lesions of chronic periodontitis.
AB  - OBJECTIVES: This study aims to compare the expression levels of interleukin (IL)
      17 and IL-23 in local periodontal tissues from patients with both chronic
      periodontitis and oral lichen planus (CP-OLP), patients with chronic
      periodontitis (CP) only, patients with oral lichen planus (OLP) only, and healthy
      controls (HC). MATERIALS AND METHODS: The periodontal tissues were collected from
      15 CP-OLP patients, 15 CP patients, 15 OLP patients, and 10 healthy controls.
      Immunohistochemistry (IHC) and real-time quantitative PCR (qPCR) was performed to
      investigate the protein and mRNA expression level of IL-17 and IL-23 in
      periodontal lesions from these four groups. RESULTS: IHC statistical analysis
      showed that the expression level of IL-17- and IL-23p19-positive cells
      significantly increased in CP-OLP group compared with that in CP (P < 0.01) and
      OLP groups (P < 0.05), showing intense staining reaction in local lamina propria
      lesions. Meanwhile, qPCR result showed higher IL-17 mRNA level in CP-OLP compared
      with that in CP and OLP groups and demonstrated a significant increase than OLP
      group (P < 0.05). Moreover, it was found that IL-17 mRNA expression level in
      erosive CP-OLP patients was significantly correlated with probing depth and
      attachment loss (P < 0.05). CONCLUSIONS: This study indicated that there was an
      increased expression level of IL-17 and IL-23 in periodontal tissues from
      periodontitis patients with oral lichen planus, which might aggravate the
      inflammatory response in local lesions. CLINICAL RELEVANCE: Oral lichen planus
      and chronic periodontitis may have interaction in disease pathogenesis, while IL
      17 detection in local lesions may be helpful in identifying the disease severity
      in periodontitis patients with oral lichen planus.

PMID- 24306679
TI  - The Basic Erosive Wear Examination (BEWE) applied retrospectively to two studies.
AB  - OBJECTIVES: A scoring method for tooth erosion is needed to enable community
      based assessments. The aim of this study was to evaluate the Basic Erosive Wear
      Examination (BEWE) scoring method, using data previously collected from two
      studies. MATERIALS AND METHODS: In a national survey of erosion in children and
      adolescents, a representative, 20 % nationwide sample of 2,251 children, aged 6,
      12 and 15 years, was examined. Erosion, recorded for all surfaces of permanent
      teeth, was converted to a BEWE score. For a group of referred patients, erosion
      was scored for 351 patients and then converted to a BEWE score. RESULTS: From the
      national survey, no erosion was seen in permanent teeth of 6 years old, but was
      present in 12 years old (19.9 % boys, mean BEWE of 0.22; 11.0 % girls, mean BEWE
      of 0.079; p < 0.001). Among 15 years old, erosion was seen in 30.7 % of subjects
      (38.3 % boys, mean BEWE of 1.00; 22.7 % girls, mean BEWE of 0.42; p < 0.001). For
      the referred patients, the BEWE score was 9.4 for subjects with gastric reflux
      symptoms but 6.0 for those without symptoms (p < 0.001). CONCLUSIONS: The value
      of scoring with the BEWE methodology was clearly demonstrated, showing increasing
      severity of erosion between 12 and 15 years and gender differences in erosion
      severity. Intrinsic acid erosion clearly caused an increased BEWE score. CLINICAL
      RELEVANCE: The BEWE scoring methodology appears valuable for assessing erosion in
      populations.

PMID- 24306680
TI  - Biochemical analysis of the articular disc of the temporomandibular joint with
      magnetic resonance T2 mapping: a feasibility study.
AB  - OBJECTIVES: Symptoms of temporomandibular joint (TMJ) dysfunction can seriously
      compromise patients' quality of life. The aim of our study was to use magnetic
      resonance imaging (MRI) T2 mapping of the articular disc to determine whether T2
      mapping of the TMJ disc is feasible in routine clinical imaging and to assess the
      normal T2 relaxation time distribution within the TMJ. METHODS: Included were ten
      asymptomatic volunteers without pain, any mouth-opening limitations, or any
      clicking phenomena. MR imaging was performed on a 3-T MR scanner using a
      flexible, dedicated, eight-channel multielement coil. T2 mapping was performed in
      the oblique sagittal plane. The regions of interest (ROIs) for the T2 relaxation
      time maps of the disc were selected manually. RESULTS: The mean values for ROIs
      ranged between 22.4 and 28.8 ms, and the mean for all ROIs was 26.0 +/- 5.0 ms.
      Intraclass correlation (ICC) for interobserver variability was 0.698, and ICC for
      intraobserver variability was 0.861. There was no statistically significant
      difference between raters (p = 0.091) or sides (p = 0.810). CONCLUSION: The T2
      mapping technique enables ultrastructural analysis of the composition of TMJ
      disc. This biochemical technique is feasible in vivo, as shown in our study, when
      a high-field (3 T) MR and a dedicated TMJ coil are used. CLINICAL RELEVANCE: T2
      mapping as a biochemical technique, together with morphological MRI, may help to
      gain more insights into the physiology and into the pathophysiology of the
      articular disc in the TMJ noninvasively and in vivo.

PMID- 24306681
TI  - Translocation and metabolism of glycine betaine by barley plants in relation to
      water stress.
AB  - The glycine betaine which accumulated in shoots of young barley plants (Hordeum
      vulgare L.) during an episode of water stress did not undergo net destruction
      upon relief of stress, but its distribution among plant organs changed. During
      stress, betaine accumulated primarily in mature leaves, whereas it was found
      mainly in young leaves after rewatering. Well-watered, stressed, and stressed
      rewatered plants were supplied with [methyl-(14)C]betaine (8.5 nmol) via an
      abraded spot on the second leaf blade, and incubated for 3 d. In all three
      treatments the added (14)C migrated more or less extensively from the second leaf
      blade, but was recovered quantitatively from various plant organs in the form of
      betaine; no labeled degradation products were found in any organ. When 0.5 MUmol
      of [methyl-(14)C]betaine was applied via an abraded spot to the second leaf
      blades of well-watered, mildly-stressed, and stressed-rewatered plants, (14)C was
      translocated out of the blades at velocities of about 0.2-0.3 cm/min which were
      similar to velocities found for applied [(14)C]sucrose. Heat-girdling of the
      sheath prevented export of [(14)C]betaine from the blade. When 0.5 MUmol
      [(3)H]sucrose and 0.5 MUmol [(14)C]betaine were suppled simultaneously to second
      leaf blades, the (3)H/(14)C ratio in the sheath tissue was the same as that of
      the supplied mixture. After supplying tracer [(14)C]betaine aldehyde (the
      immediate precursor of betaine) to the second leaf blade, the (14)C which was
      translocated into the sheath was in the form of betaine. Thus, betaine
      synthesized by mature leaves during stress behaves as an inert end product and
      upon rewatering is translocated to the expanding leaves, most probably via the
      phloem. Accordingly, it is suggested that the level of betaine in a barley plant
      might serve as a useful cumulative index of the water stress experienced during
      growth. 

PMID- 24306682
TI  - Use of an (n, alpha) nuclear reaction to study the long-distance transport of
      boron in trifolium repens after foliar application.
AB  - The growth of white clover (Trifolium repens L.) is severely inhibited by boron
      starvation, but a foliar treatment with boric acid can transitorily alleviate the
      deficiency symptoms. The (10)B(n ,alpha)(7) Li nuclear reaction has been used to
      study boron transport in the plant after foliar application. More than 98% of the
      boron supplied remained at the point where it was applied to the leaves, and less
      than 2% was useful to the growth of the treated plant. This small "efficient"
      portion of boron was quite mobile. It was distributed to the different parts of
      the plant, then was transferred from the oldest parts to the newly formed leaves.
      Physiological and agronomical implications of these data are discussed. 

PMID- 24306683
TI  - Correlation between 5-aminolaevulinate accumulation and protochlorophyll
      photoconversion.
AB  - A 1-min light pulse delivered to mustard seedlings (Sinapis alba L.) 60 h after
      sowing initiates the release of cotyledonary 5-aminolaevulinate (ALA)
      accumulation which continues for at least 2 h in the dark. Phytochrome (P fr)
      increases the rate of ALA accumulation after a 24-h red light pretreatment but is
      not the trigger for this release. It is shown that the rate of ALA accumulation
      varies with the wave-length and fluence rate of the 1-min light pulse and can be
      predicted from the degree of protochlorophyll-(ide) photoconversion. There is a
      linear correlation between the rate of ALA accumulation and the degree of
      protochlorophyll(ide) (PChl)->chlorophyll(ide) a (Chl a) photoconversion in
      etiolated seedlings. In seedlings pretreated with red light this correlation is
      non-linear and the rate increases more rapidly with increasing degrees of PChl
      >Chl a photoconversion. It is suggested that there may exist an interaction
      between P fr and PChl->Chl a photoconversion in controlling ALA accumulation. 

PMID- 24306684
TI  - Ultrastructural investigations on Lycopersicum peruvianum pollen activation and
      pollen tube organization after self-and cross-pollination.
AB  - No differences have been observed "in vivo" between Lycopersicum peruvianum
      compatible and incompatible pollen during activation and pollen tube emission and
      organization, that is until 4 h and 30 min after pollination. During pollen
      activation the main events are the setting free of rough endoplasmic reticulum
      (RER) cisterns which were "stacked" in the mature pollen, the increase in the
      number of polysomes, and a great activity of the dictyosomes. Immediately after
      germination of the vegetative nucleus and the generative cell move into the tube,
      the generative cell diviting to form the male gametes; the tube then becomes
      organized in four zones. This series of changes is similar to what has already
      been observed "in vitro" except that in vitro the generative cell remains
      undivided and the whole process from seeding to tube organization takes 3 h
      instead of 4 h and 30 min after pollination, as it does in vivo. Our findings are
      compatible with the main models of the tube inhibition mechanism proposed till
      now. 

PMID- 24306685
TI  - Promotion of stomatal opening in the grass Anthephora pubescens nees by a range
      of natural and synthetic cytokinis.
AB  - Stomatal opening in detached epidermis of Anthephora pubescens Nees incubated in
      the light and CO2-free air was enhanced by each of 6 natural and 4 synthetic
      cytokinis. Apertures were maximal following incubation with 10 mmol m(-3)
      cytokinin in PIPES buffer for all except N(6)-[Delta (2)-isopentyl] adenine and
      N(6)-[Delta (2)-sopentyl] adenosine which both opened stomata maximally at 0.1
      mmol m(-3). Experiments which were undertaken to optimise the conditions of
      incubation showed that opening was maximal after 3 h incubation and that while 10
      mmol m(-3) kinetin increased the rate of stomatal opening, it did not affect the
      duration. Exogenous KCl was not needed for opening and light was saturating even
      at the low level of 140 MUmol m(-2) s(-1). 

PMID- 24306686
TI  - ATPase and acid phosphatase activities associated with vacuoles isolated from
      storage roots of red beet (Beta vulgaris L.).
AB  - Phosphatase activities were measured in preparations of vacuoles isolated from
      storage roots of red beet (Beta vulgaris L.). The vacuoles possessed both acid
      phosphatase and ATPase activities which could be distinguished by their
      susceptibility to inhibition by low concentrations of ammonium molybdate
      [(NH4)6Mo7O24.4H2O]. The acid phosphatase was completely inhibited by 100 MUM
      ammonium molybdate but the ATPase was unaffected. The acid phosphatase was a
      soluble enzyme which hydrolysed a large number of phosphate esters and had a pH
      optimum of 5.5. In contrast, the ATPase was partially membrane-bound, had a pH
      optimum of 8.0 and hydrolysed ATP preferentially, although it was also active
      agianst PPi, GTP and GDP. At pH 8.0 both the ATPase and PPase activities were
      Mg(2+)-dependent and were further stimulated by KCl. The ATPase and PPase
      activities at pH 8.0 may be different enzymes. The recovery and purification of
      the ATPase during vacuole isolation were determined. The results indicate that
      the Mg(2+)-dependent, KCl-stimulated ATPase activity is not exclusively
      associated with vacuoles. 

PMID- 24306687
TI  - Amino acid uptake by Lemna gibba by a mechanism with affinity to neutral L-and D
      amino acids.
AB  - Earlier work suggested that amino acid uptake by Lemna gibba cells is a H(+)
      cotransport mechanism driven by a proton-electrochemical gradient at the
      plasmalemma. The present investigations of the transient membrane depolarizations
      elicited by amino acids and tracer-uptake experiments show that all neutral alpha
      L-amino acids, D-alanine and analogues, like beta-alanine and p
      fluorophenylalanine, are transported by the same system. It remains to be seen if
      there are separate mechanisms for the uptake of acidic and basic amino acids. 

PMID- 24306688
TI  - Variability of mitochondrial population in Chlamydomonas reinhardii.
AB  - Several details have been published cocerning the mitochondrial number and shapes
      at various stages of the synchronized vegetative and generative cell cycle in
      Chlamydomonas reinhardii. The present study, based on ultrathin serial sections
      and threedimensional reconstructions, completes these data. Quantitative analysis
      of serial micrographs makes it possible to give specific details of mitochondrial
      volumes in cells at early intermediate stages of the vegetative life cycle. Our
      investigations clearly show that mitochondria have a relatively wide range of
      sizes, within certain limits, and vary like the mitochondrial shapes; in fact,
      they vary in various cells at various stages as well as in several cells at the
      same stage and even in one and the same cell. Thus, we present a plastic insight
      into the dynamically changing micromorphology of the mitochondrial population in
      Chlamydomonas reinhardii. 

PMID- 24306689
TI  - The reactivation of nitrate reductase from spinach (Spinacia oleracea L.)
      inactivated by NADH and cyanide, using trivalent manganese either generated by
      illuminated chloroplasts or as manganipyrophosphate.
AB  - Nitrate reductase of spinach (Spinacia oleracea L.) leaves which had been
      inactivated in vitro by treatment with NADH and cyanide, was reactivated by
      incubation with oxidant systems and measured as FMNH2-dependent activity.
      Reactivation was produced with trivalent manganese compounds represented either
      by manganipyrophosphate or produced by oxidation of Mn(2+) ions in the presence
      of illuminated chloroplasts and compared with reactivation obtained with
      ferricyanide. Reactivation in the chloroplast system was equivalent to that with
      ferricyanide when orthophosphate was used but was variable and weak in the
      presence of pyrophosphate, although manganipyrophosphate was formed, freely.
      Reactivation by manganipyrophosphate in dark reaction conditions was less
      effective than with ferricyanide but was not inhibited by the addition of
      pyrophosphate. Reactivation with illuminated unheated chloroplasts was dependent
      on added manganese and oxidation of manganese in the presence of pyrophosphate
      was abolished by boiling the chloroplasts. In the presence of orthophosphate
      however, boiled, illuminated chloroplasts reactivated the enzyme in the absence
      of added manganese. Reactivation occurred spontaneously in air, more slowly than
      with the other oxidants, but to a similar extent to that produced by
      manganipyrophosphate. The results provide a possible model for physiological
      reactivation mechanisms. 

PMID- 24306690
TI  - Polysomes and intracisternal accumulations in enucleate sieve elements of rice
      (Oryza sativa L.).
AB  - Polysomes in sieve elements of rice (Oryza sativa L.) were studied with the
      electron microscope. The polysomes were found on the rough endoplasmic reticulum
      (ER) present in immature sieve elements and also on the cisternae of aggregated
      ER in the parietal layer of mature, enucleate sieve elements. In the immature
      sieve elements the ER cisternae existed as narrow profiles while in the mature
      sieve elements the ER cisternae were considerably dilated and contained a
      fibrillar material and, occasionally, electron-opaque inclusions. In addition to
      the aggregated ER, single profiles of ER were found applied to the lateral walls
      and also the sieve plates. These cisternae also bore ribosomes and were separated
      from the plasmalemma by a narrow, dense space. In the mature sieve elements much
      of the surface of the ER membranes was covered with polysomes. The dimensions of
      the polysomes are described and the possibility that they contribute to the
      formation of the fibrillar material in the intracisternal space is discussed. 

PMID- 24306691
TI  - Role of auxin and sucrose in the differentiation of sieve and tracheary elements
      in plant tissue cultures.
AB  - The differentiation of sieve and tracheary elements was studied in callus culture
      of Daucus carota L., Syringa vulgaris L., Glycine max (L.) Merr., Helianthus
      annuus L., Hibiscus cannabinus L. and Pisum sativum L. By the lacmoid clearing
      technique it was found that development of the phloem commenced before that of
      the xylem. In not one of the calluses was differentiation of tracheary elements
      observed in the absence of sieve elements. The influence of indole-3-acetic acid
      (IAA) and sucrose was evaluated quantitatively in callus of Syringa, Daucus and
      Glycine. Low IAA levels resulted in the differentiation of sieve elements with no
      tracheary cells. High levels resulted in that of both phloem and xylem. IAA thus
      controlled the number of sieve and tracheary elements, increase in auxin
      concentration boosting the number of both cell types. Changes in sucrose
      concentration, while the IAA concentration was kept constant, did not have a
      specific effect on either sieve element differentiation, or on the ratio between
      phloem and xylem. Sucrose did, however, affect the quantity of callose deposited
      on the sieve plates, because increase in the sucrose concentration resulted in an
      increase in the amount of callose. It is proposed that phloem is formed in
      response to auxin, while xylem is formed in response to auxin together with some
      added factor which reaches it from the phloem. 

PMID- 24306692
TI  - Factors influencing the incidence of habituation for cytokinin of tobacco pith
      tissue in culture.
AB  - Pith tissue of Nicotiana tabacum L. cv. "Havana 425" exhibits a gradient in its
      tendency to habituate for cytokinin on an auxin-containing medium at 35 degrees 
      C, about 10 degrees  C above the standard culture temperature. Explants of pith
      from below the 8th to 11th internode, counting from the bottom of the plant,
      rarely habituate for cytokinin; explants from above this threshold habituate
      rapidly. The explants must also be above a critical size, about 20-30 mg, to
      habituate. There was a pronounced interaction between size and position effects;
      the threshold position for cytokinin habituation shifted upward with decreasing
      explant size. 

PMID- 24306693
TI  - Molecular characterisation and evolution of HMW glutenin subunit genes in
      Brachypodium distachyon L.
AB  - Brachypodium distachyon, a small wild grass within the Pooideae family, is a new
      model organism for exploring the functional genomics of cereal crops. It was
      shown to have close relationships to wheat, barley and rice. Here, we describe
      the molecular characterisation and evolutionary relationships of high molecular
      weight glutenin subunits (HMW-GS) genes from B. distachyon. Sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), high performance
      capillary electrophoresis (HPCE) and liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) analyses demonstrated that there was no HMW-GS expression
      in the Brachypodium grains due to the silencing of their encoding genes. Through
      allele-specific polymerase chain reaction (AS-PCR) amplification and cloning, a
      total of 13 HMW-GS encoding genes from diploid, tetraploid and hexaploid
      Brachypodium species were obtained, and all of them had typical structural
      features of y-type HMW-GS genes from common wheat and related species,
      particularly more similar to the 1Dy12 gene. However, the presence of an in-frame
      premature stop codon (TAG) at position 1521 in the coding region resulted in the
      conversion of all the genes to pseudogenes. Further, quantitative real-time PCR
      (qRT-PCR) analysis revealed that HMW-GS genes in B. distachyon displayed a
      similar trend, but with a low transcriptional expression profile during grain
      development due to the occurrence of the stop codon. Phylogenetic analysis showed
      that the highly conserved Glu-1-2 loci were presented in B. distachyon, which
      displayed close phylogenetic evolutionary relationships with Triticum and related
      species. 

PMID- 24306694
TI  - The natural progression of synovial fluid white blood-cell counts and the
      percentage of polymorphonuclear cells after primary total knee arthroplasty: a
      multicenter study.
AB  - BACKGROUND: Assessments of the synovial fluid white blood-cell (WBC) count and
      percentage of polymorphonuclear cells (PMNs) have been reported to be useful in
      the diagnosis of periprosthetic joint infection. The purpose of this multicenter
      retrospective study was to evaluate the natural progression of the synovial fluid
      WBC count, PMN percentage, and total neutrophil count in patients who underwent
      knee aspiration during the first two years after primary total knee arthroplasty
      and had no evidence of periprosthetic joint infection. METHODS: From April 1999
      to March 2012, 571 patients who presented within the first two years after
      primary total knee arthroplasty underwent knee aspiration as part of an
      evaluation for periprosthetic joint infection. Patients were categorized into
      four groups on the basis of the number of days between surgery and
      arthrocentesis. The synovial fluid WBC count, PMN percentage, and total
      neutrophil count were compared among the four time periods with use of separate
      one-way analyses of variance and Tamhane post-hoc analyses. RESULTS: Four hundred
      and fifty-two samples not associated with a periprosthetic joint infection were
      adequate for analysis. The synovial fluid WBC count, PMN percentage, and total
      neutrophil count all decreased after the first ninety postoperative days. The
      synovial fluid WBC count showed an earlier return to a level similar to the two
      year time point than the PMN percentage did. The mean total neutrophil count
      decreased from 2533.2 cells/MUL during the first forty-five days to 649.0
      cells/MUL from forty-six to ninety days, 269.5 cells/MUL from three months to one
      year, and 240.8 cells/MUL from one to two years. CONCLUSIONS: The synovial fluid
      WBC count and PMN percentage changed at different rates over the first two years
      after total knee arthroplasty, with the WBC count exhibiting an initially more
      rapid decrease and the PMN percentage demonstrating a more linear decrease.
      Hence, the total neutrophil count, which combines these two parameters, may
      provide a better method to identify patients with a periprosthetic joint
      infection. Values for the synovial fluid WBC count, PMN percentage, and total
      neutrophil count were all significantly elevated in the early postoperative
      period, and the use of standard cutoff values for the diagnosis of periprosthetic
      joint infection can lead to false-positive results.

PMID- 24306695
TI  - Efficacy and safety of recombinant human bone morphogenetic protein-2/calcium
      phosphate matrix for closed tibial diaphyseal fracture: a double-blind,
      randomized, controlled phase-II/III trial.
AB  - BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) applied on
      an absorbable collagen sponge improves open tibial fracture-healing as an adjunct
      to unreamed intramedullary nail fixation. We evaluated rhBMP-2 and a new,
      injectable calcium phosphate matrix (CPM) formulation in acute closed tibial
      diaphyseal fractures treated with reamed intramedullary nail fixation. METHODS:
      Patients were randomized (1:2:2:1) to receive standard of care, which consisted
      of definitive fracture fixation within seventy-two hours of injury with a locked
      intramedullary nail after reaming; standard of care and injection with 1.0 mg/mL
      of rhBMP-2/CPM; standard of care and injection with 2.0 mg/mL of rhBMP-2/CPM; or
      standard of care and injection with buffer/CPM, to evaluate the activity of the
      CPM delivery matrix and provide for sponsor and investigator blinding. The co
      primary end points of the study were the effects of rhBMP-2/CPM on the time to
      fracture union (based on blinded assessment of radiographs) and the time to
      return to normal function (based on blinded assessment of the time to full weight
      bearing without pain at the fracture site) compared with standard of care alone.
      RESULTS: Three hundred and sixty-nine patients were randomized and included in
      the intent-to-treat population. This study was terminated after an interim
      analysis (180 patients with six months of follow-up) revealed no shortening in
      the time to fracture union in the active treatment arms compared with the
      standard of care control (the SOC group). In the final primary analysis, the
      median time to radiographic fracture union was not significantly different for
      the SOC (13.1 weeks), 1.0-mg/mL rhBMP-2/CPM (13.0 weeks), 2.0-mg/mL rhBMP-2/CPM
      (15.9 weeks), or buffer/CPM (15.4 weeks) treatment groups. The median time to
      pain-free full weight-bearing was also not significantly different among the SOC
      (13.4 weeks), 1.0-mg/mL rhBMP-2/CPM (13.4 weeks), 2.0-mg/mL rhBMP-2/CPM (14.3
      weeks), and buffer/CPM (16.4 weeks) treatment groups. CONCLUSIONS: In patients
      with closed tibial fractures treated with reamed intramedullary nailing, the time
      to fracture union and pain-free full weight-bearing were not significantly
      reduced by rhBMP-2/CPM compared with standard of care alone. 24306696

PMID- 24306696
TI  - Learning curve for new technology?: a nationwide register-based study of 46,363
      total knee arthroplasties.
AB  - BACKGROUND: The risk of early revision is increased for the first patients
      operatively treated with a newly introduced knee prosthesis. In this study, we
      explored the learning curves associated with ten knee implant models to determine
      their effect on early revision risk. METHODS: We studied register data from all
      seventy-five surgical units that performed knee arthroplasty in Finland from 1998
      to 2007. Of 54,925 patients (66,098 knees), 39,528 patients (46,363 knees)
      underwent arthroplasty for osteoarthritis of the knee with the ten most common
      total knee implants and were followed with complete data until December 31, 2010,
      or the time of death. We used a Cox proportional-hazards regression model for
      calculating the hazard ratios for early revision for the first fifteen
      arthroplasties and subsequent increments of numbers of arthroplasties. RESULTS:
      We found large differences among knee implants at the introduction with regard to
      the risk of early revision, as well as for the overall risk of early revision. A
      learning curve was found for four implant models, while six models did not show a
      learning effect on the risk of early revision. The survivorship of the studied
      prostheses showed substantial differences. CONCLUSIONS: Knee implants have model
      specific learning curves and early revision risks. Some models are more difficult
      to implement than others. The manufacturers should consider the learning effect
      when designing implants and instrumentation. The surgeons should thoroughly
      familiarize themselves with the new knee implants before use.

PMID- 24306699
TI  - The surgical anatomy of the infrapatellar branch of the saphenous nerve in
      relation to incisions for anteromedial knee surgery.
AB  - BACKGROUND: Iatrogenic injury to the infrapatellar branch of the saphenous nerve
      is a common complication of surgical approaches to the anteromedial side of the
      knee. A detailed description of the relative anatomic course of the nerve is
      important to define clinical guidelines and minimize iatrogenic damage during
      anterior knee surgery. METHODS: In twenty embalmed knees, the infrapatellar
      branch of the saphenous nerve was dissected. With use of a computer-assisted
      surgical anatomy mapping tool, safe and risk zones, as well as the location
      dependent direction of the nerve, were calculated. RESULTS: The location of the
      infrapatellar branch of the saphenous nerve is highly variable, and no definite
      safe zone could be identified. The infrapatellar branch runs in neither a purely
      horizontal nor a vertical course. The course of the branch is location-dependent.
      Medially, it runs a nearly vertical course; medial to the patellar tendon, it has
      a -45 degrees  distal-lateral course; and on the patella and patellar tendon, it
      runs a close to horizontal-lateral course. Three low risk zones for iatrogenic
      nerve injury were identified: one is on the medial side of the knee, at the level
      of the tibial tuberosity, where a -45 degrees  oblique incision is least prone to
      damage the nerves, and two zones are located medial to the patellar apex (cranial
      and caudal), where close to horizontal incisions are least prone to damage the
      nerves. CONCLUSIONS: The infrapatellar branch of the saphenous nerve is at risk
      for iatrogenic damage in anteromedial knee surgery, especially when longitudinal
      incisions are made. There are three low risk zones for a safer anterior approach
      to the knee. The direction of the infrapatellar branch of the saphenous nerve is
      location-dependent. To minimize iatrogenic damage to the nerve, the direction of
      incisions should be parallel to the direction of the nerve when technically
      possible. CLINICAL RELEVANCE: These findings suggest that iatrogenic damage of
      the infrapatellar branch of the saphenous nerve can be minimized in anteromedial
      knee surgery when both the location and the location-dependent direction of the
      nerve are considered when making the skin incision.

PMID- 24306698
TI  - Management of failures of total ankle replacement with the agility total ankle
      arthroplasty.
AB  - BACKGROUND: Few studies have focused on treatment following failed total ankle
      replacement. The purpose of this study was to report the outcomes of patients
      undergoing revision total ankle replacement and to propose a talar component
      subsidence grading system that may be helpful in making decisions regarding how
      to revise failed total ankle replacements in the future. METHODS: A retrospective
      review was performed of fifty-three patients who underwent revision total ankle
      replacement and had been followed for a minimum of two years. Patients were
      assessed radiographically and with outcome scores. The rates of conversion to
      amputation or fusion were also assessed. RESULTS: The mean follow-up period was
      49.1 months after the revision arthroplasty. The average time from primary total
      ankle replacement to revision was fifty-one months. Forty-one of the fifty-three
      patients (77%) were available for follow-up. The revision arthroplasty had been
      converted to an arthrodesis in five of the forty-one patients, and two additional
      patients had undergone amputation. The most common indication for revision total
      ankle replacement was talar subsidence (63%; twenty-six of forty-one). Twenty-two
      patients (54%) had a subtalar arthrodesis performed at the time of the revision
      arthroplasty, with nineteen of those having a custom-designed long-stem talar
      component placed simultaneously. The mean radiographic measurements of component
      position did not change significantly postoperatively. The mean postoperative
      scores for the thirty-four patients with a retained total ankle replacement were:
      4.4 of 10 possible points on a visual analog pain scale (VAS), 65 of 100 possible
      points on the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scale,
      93.5 of 100 possible points on the Short-Form 12 (SF-12), 137.9 of 204 possible
      points on the Revised Foot Function Index (FFI-R), and 64 of 180 possible points
      on the Ankle Osteoarthritis Scale (AOS). The mean arc of motion radiographically
      was 18 degrees  preoperatively and 23 degrees  postoperatively, with all
      improvement occurring in plantar flexion. A lesser amount of preoperative talar
      subsidence was a significant predictor of a good outcome based on the AOFAS
      hindfoot score (p < 0.03) and the AOS (p < 0.01) score. CONCLUSIONS: Revision
      arthroplasty may be considered as an alternative to arthrodesis when treating
      patients with a failed Agility total ankle implant.

PMID- 24306697
TI  - The association between perioperative allogeneic transfusion volume and
      postoperative infection in patients following lumbar spine surgery.
AB  - BACKGROUND: Perioperative allogeneic red blood cell transfusion is a risk factor
      for surgical site infection. The purpose of this study was to determine if the
      volume of perioperative allogeneic red blood cell transfusion influences the risk
      of surgical site infection following lumbar spine procedures. METHODS: A
      retrospective matched case control study was performed by reviewing all patients
      who had undergone lumbar spine surgery at our institution from 2005 to 2009.
      Surgical site infections (spinal or iliac crest) were identified, all within
      thirty days of the procedure. Controls were matched to the infection cohort
      according to age, sex, body mass index, diabetic status, smoking status, Charlson
      Comorbidity Index, length of surgery, and procedure. A conditional logistic
      regression was performed to examine the association between transfusion volume
      and surgical site infection. The results were summarized by an odds ratio.
      RESULTS: A total of 1799 lumbar procedures were identified with an infection rate
      of 3.1% (fifty-six cases). On the basis of the numbers, there was no significant
      difference in the matched variables between the infection cohort and the matched
      controls. The volume of transfusion was significantly associated with surgical
      site infection (odds ratio, 4.00 [95% confidence interval, 1.96 to 8.15]) after
      adjusting for both unmatched variables of preoperative hemoglobin level and
      volume of intraoperative blood loss. CONCLUSIONS: In this retrospective matched
      case control study, the association between surgical site infection following
      lumbar spine surgery and volume of perioperative allogeneic red blood cell
      transfusion was supported.

PMID- 24306700
TI  - Digit replantation: experience of two U.S. academic level-I trauma centers.
AB  - BACKGROUND: Despite advances in microsurgery, digit replantation now is performed
      less frequently in the U.S. compared with fifteen years ago. There has been
      uncertainty regarding whether previously reported U.S. replantation success rates
      and results reported from other countries reflect the current experience in the
      U.S. We hypothesized that the success of digit replantation at two academic level
      I referral hospitals in the U.S. would be similar to previously published
      results. METHODS: In this retrospective case series, we examined all cases of
      digit replantation that were performed from 1997 through 2010 at two
      institutions. The cumulative rate of viable digit replantations was determined.
      Binary logistic regression modeling determined the relative impact of patient,
      injury, and operative factors on replantation survival. RESULTS: During the study
      period, 135 digit replantations were performed in 106 patients. Fourteen cases
      did not meet our inclusion criteria, yielding a cohort of 121 replantations. The
      thumb (n = 40) was the most commonly replanted digit, followed by the long finger
      (n = 31). The mechanism of injury was classified as sharp in eighty-three digits,
      crush in nineteen digits, and avulsion in eighteen digits. The majority of
      replantations were performed following Tamai level-III (n = 49) or level-IV (n =
      56) amputations. Sixty-nine (57%) of the digit replantation procedures were
      successful. Logistic regression analysis identified replantation of the radial
      three digits and no history of tobacco use as significant independent predictors
      of replantation success. CONCLUSIONS: The rate of success of digit replantation
      (57%) at two academic level-I trauma hospitals was lower than previously
      published rates. Radial-digit involvement and no prior tobacco use were
      associated with replantation success. This modest success rate reflects a need
      for additional evaluation of our current benchmarks and clinical settings for
      replantation surgery. These data help to better inform patients, families, and
      physicians who are considering digit replantation.

PMID- 24306701
TI  - Lateral mass screw fixation in the cervical spine: a systematic literature
      review.
AB  - BACKGROUND: Lateral mass screw fixation with plates or rods has become the
      standard method of posterior cervical spine fixation and stabilization for a
      variety of surgical indications. Despite ubiquitous usage, the safety and
      efficacy of this technique have not yet been established sufficiently to permit
      "on-label" U.S. Food and Drug Administration approval for lateral mass screw
      fixation systems. The purpose of this study was to describe the safety profile
      and effectiveness of such systems when used in stabilizing the posterior cervical
      spine. METHODS: A systematic search was conducted in MEDLINE and the Cochrane
      Collaboration Library for articles published from January 1, 1980, to December 1,
      2011. We included all articles evaluating safety and/or clinical outcomes in
      adult patients undergoing posterior cervical subaxial fusion utilizing lateral
      mass instrumentation with plates or rods for degenerative disease (spondylosis),
      trauma, deformity, inflammatory disease, and revision surgery that satisfied our
      a priori inclusion and exclusion criteria. RESULTS: Twenty articles (two
      retrospective comparative studies and eighteen case series) satisfied the
      inclusion and exclusion criteria and were included. Both of the comparative
      studies involved comparison of lateral mass screw fixation with wiring and
      indicated that the risk of complications was comparable between treatments
      (range, 0% to 7.1% compared with 0% to 6.3%, respectively). In one study, the
      fusion rate reported in the screw fixation group (100%) was similar to that in
      the wiring group (97%). Complication risks following lateral mass screw fixation
      were low across the eighteen case series. Nerve root injury attributed to screw
      placement occurred in 1.0% (95% confidence interval, 0.3% to 1.6%) of patients.
      No cases of vertebral artery injury were reported. Instrumentation complications
      such as screw or rod pullout, screw or plate breakage, and screw loosening
      occurred in <1% of the screws inserted. Fusion was achieved in 97.0% of patients
      across nine case series. CONCLUSIONS: The risks of complications were low and the
      fusion rate was high when lateral mass screw fixation was used in patients
      undergoing posterior cervical subaxial fusion. Nerve root injury attributed to
      screw placement occurred in only 1% of 1041 patients. No cases of vertebral
      artery injury were identified in 758 patients. Screw or rod pullout, screw or
      plate breakage, and screw loosening occurred in <1% of the screws inserted.

PMID- 24306702
TI  - Peripheral nerve repair and reconstruction.
AB  - When possible, direct repair remains the current standard of care for the repair
      of peripheral nerve lacerations. In large nerve gaps, in which direct repair is
      not possible, grafting remains the most viable option. Nerve scaffolds include
      autologous conduits, artificial nonbioabsorbable conduits, and bioabsorbable
      conduits and are options for repair of digital nerve gaps that are <3 cm in
      length. Experimental studies suggest that the use of allografts may be an option
      for repairing larger sensory nerve gaps without associated donor-site morbidity.

PMID- 24306704
TI  - Origin of propionibacterium in surgical wounds and evidence-based approach for
      culturing propionibacterium from surgical sites.
AB  - BACKGROUND: To explore the origin of Propionibacterium in surgical wounds and to
      suggest an optimized strategy for culturing this organism at the time of revision
      surgery, we studied the presence of this organism on the skin and in the surgical
      wounds of patients who underwent revision arthroplasty for reasons other than
      apparent infection. METHODS: Specimens were cultured in broth and on aerobic and
      anaerobic media. The presence and degree of positivity of Propionibacterium
      cultures were correlated with sex. The results of dermal and deep cultures were
      correlated. Times to positivity and the yields of each media type and specimen
      source were investigated. RESULTS: Propionibacterium grew in twenty-three of
      thirty cultures of specimens obtained preoperatively from the unprepared
      epidermis over the area where a skin incision was going to be made for a shoulder
      arthroplasty; males had a greater average degree of positivity than females (p <
      0.002). Twelve of twenty-one male subjects and zero of twenty female subjects who
      had cultures of dermal specimens obtained during revision shoulder arthroplasty
      had positive findings for Propionibacterium (p = 0.0001). Twelve of twenty male
      subjects and only one of twenty female subjects had positive deep cultures (p =
      0.0004). The positivity of dermal cultures for Propionibacterium was
      significantly associated with the positivity of deep cultures for this organism
      (p = 0.0001). If Propionibacterium was present in deep tissues, it was likely
      that it would be recovered by culture if four different specimens were obtained
      and cultured for a minimum of seventeen days on three different media: aerobic,
      anaerobic, and broth. CONCLUSIONS: Because the surgical incision of dermal
      sebaceous glands may be a source of Propionibacterium in deep wounds, strategies
      for minimizing the risk of Propionibacterium infections may need to be directed
      at minimizing the contamination of surgical wounds from these bacteria residing
      in rather than on the skin. Obtaining at least four specimens, observing them for
      seventeen days, and using three types of culture media optimize the recovery of
      Propionibacterium at the time of revision surgery.

PMID- 24306705
TI  - Assessment of femoral head and head-neck junction perfusion following surgical
      hip dislocation using gadolinium-enhanced magnetic resonance imaging: a cadaveric
      study.
AB  - BACKGROUND: The purpose of the present study was to quantify perfusion to the
      femoral head and head-neck junction using gadolinium-enhanced magnetic resonance
      imaging following three surgical dislocations of the hip (trochanteric flip
      osteotomy, standard posterior approach, and modified posterior approach).
      METHODS: The medial femoral circumflex artery was cannulated in fifty fresh
      frozen cadaveric hips (twenty-five pelvic specimens). One hip on each pelvic
      specimen was randomly chosen to undergo one of the three surgical dislocations,
      and the contralateral hip was used as a control. Gadolinium enhancement on the
      magnetic resonance imaging scan was quantified in both the femoral head and head
      neck junction by volumetric analysis using custom magnetic resonance imaging
      analysis software. A polyurethane compound was then injected, and gross
      dissection was performed to assess the extraosseous vasculature. RESULTS:
      Magnetic resonance imaging quantification revealed that the trochanteric flip
      osteotomy group maintained almost full perfusion (mean, 96% for the femoral head
      and 98% for the head-neck junction). The standard posterior approach almost
      completely compromised perfusion (mean, 4% for the femoral head and 8% for the
      head-neck junction). Six specimens in the modified posterior approach group
      demonstrated partial perfusion (mean, 32% in the femoral head and 26% in the head
      neck junction). Three specimens in the modified posterior approach group
      demonstrated almost full perfusion (mean, 96% in the femoral head and 97% in the
      head-neck junction). Gross dissection revealed that all specimens in the standard
      posterior approach group and seven of ten in the modified posterior approach
      group sustained disruption of the ascending branch of the medial femoral
      circumflex artery. All specimens in the standard posterior approach group
      demonstrated disruption of the inferior retinacular artery. The inferior
      retinacular artery remained intact in nine of ten specimens in the modified
      posterior approach group. One specimen in the modified posterior approach group
      that had disruption of both the ascending medial femoral circumflex artery and
      inferior retinacular artery demonstrated a substantial decrease in perfusion (7%
      in the femoral head and 5% in the head-neck junction). CONCLUSIONS: The
      trochanteric flip osteotomy preserves the vascular supply to the femoral head and
      head-neck junction. The standard posterior approach disrupts the vascular supply
      and should be completely abandoned for surgical hip dislocation. Despite reduced
      enhancement, substantial perfusion of the femoral head and head-neck junction was
      present in the modified posterior approach group, likely because of the
      preservation of the inferior retinacular artery. The modified posterior approach
      produced variable results, indicating that improvement to the modified posterior
      approach is needed. CLINICAL RELEVANCE: Our study provides previously unreported
      quantitative magnetic resonance imaging data on the perfusion to the femoral head
      and head-neck junction during common surgical approaches to the hip.

PMID- 24306706
TI  - EOS low-dose radiography: a reliable and accurate upright assessment of lower
      limb lengths.
AB  - BACKGROUND: Children with lower-limb-length discrepancy require repeated
      radiographic assessment for monitoring and as a guide for management. The need
      for accurate assessment of length and alignment is balanced by the need to
      minimize radiation exposure. We compared the accuracy, reliability, and radiation
      dose of EOS, a novel low-dose upright biplanar radiographic imaging system, at
      two different settings, with that of conventional radiographs
      (teleoroentgenograms) and computed tomography (CT) scanograms, for the assessment
      of limb length. METHODS: A phantom limb in a standardized position was assessed
      ten times with each of four different imaging modalities (conventional
      radiographs, CT scanograms, EOS-Slow, EOS-Fast). A radiation dosimeter was placed
      on the phantom limb, on a portion closest to the radiation source for each
      modality, in order to measure skin-entrance radiation dose. Standardized
      measurements of bone lengths were made on each image by consultant orthopaedic
      surgeons and residents and then were assessed for accuracy and reliability.
      RESULTS: The mean absolute difference from the true length of the femur was
      significantly lower (most accurate) for the EOS-Slow (2.6 mm; 0.5%) and EOS-Fast
      (3.6 mm; 0.8%) protocols as compared with CT scanograms (6.3 mm; 1.3%) (p <
      0.0001), and conventional radiographs (42.2 mm; 8.8%) (p < 0.0001). There was no
      significant difference in accuracy between the EOS-Slow and EOS-Fast protocols (p
      = 0.48). The mean radiation dose was significantly lower for the EOS-Fast
      protocol (0.68 mrad; 95% confidence interval [CI], 0.60 to 0.75 mrad) compared
      with the EOS-Slow protocol (13.52 mrad; 95% CI, 13.45 to 13.60 mrad) (p <
      0.0001), CT scanograms (3.74 mrad; 95% CI, 3.67 to 3.82 mrad) (p < 0.0001), and
      conventional radiographs (29.01 mrad; 95% CI, 28.94 to 29.09 mrad) (p < 0.0001).
      Intraclass correlation coefficients showed excellent (>0.90) agreement for
      conventional radiographs, the EOS-Slow protocol, and the EOS-Fast protocol.
      CONCLUSIONS: Upright EOS protocols that utilize a faster speed and lower current
      are more accurate than CT scanograms and conventional radiographs for the
      assessment of length and also are associated with a significantly lower radiation
      exposure. In addition, the ability of this technology to obtain images while
      subjects are standing upright makes this the ideal modality with which to assess
      limb alignment in the weight-bearing position. This method has the potential to
      become the new standard for repeated assessment of lower-limb lengths and
      alignment in growing children. CLINICAL RELEVANCE: This study assesses the
      reliability and accuracy of a diagnostic test used for clinical decision-making.

PMID- 24306707
TI  - Assessment of three-dimensional lumbar spine vertebral motion during gait with
      use of indwelling bone pins.
AB  - BACKGROUND: This study quantifies the three-dimensional motion of lumbar
      vertebrae during gait via direct in vivo measurement with the use of indwelling
      bone pins with retroreflective markers and motion capture. Two previous studies
      in which bone pins were used were limited to instrumentation of two vertebrae,
      and neither evaluated motions during gait. While several imaging-based studies of
      spinal motion have been reported, the restrictions in measurement volume that are
      inherent to imaging modalities are not conducive to gait applications. METHODS:
      Eight healthy volunteers with a mean age of 25.1 years were screened to rule out
      pathology. Then, after local anesthesia was administered, two 1.6-mm Kirschner
      wires were inserted into the L1, L2, L3, L4, L5, and S1 spinous processes. The
      wires were clamped together, and reflective marker triads were attached to the
      end of each wire couple. Subjects underwent spinal computed tomography to
      anatomically register each vertebra to the attached triad. Subjects then walked
      several times in a calibrated measurement field at a self-selected speed while
      motion data were collected. RESULTS: Less than 4 degrees  of lumbar
      intersegmental motion was found in all planes. Motions were highly consistent
      between subjects, resulting in small group standard deviations. The largest
      motions were in the coronal plane, and the middle lumbar segments exhibited
      greater motions than the segments cephalad and caudad to them. Intersegmental
      lumbar flexion and axial rotation motions were both extremely small at all
      levels. CONCLUSIONS: The lumbar spine chiefly acts to contribute abduction during
      stance and adduction during swing to balance the relative motions between the
      trunk and pelvis. The lumbar spine acts in concert with the thoracic spine. While
      the lumbar spine chiefly contributes coronal plane motion, the thoracic spine
      contributes the majority of the transverse plane motion. Both contribute flexion
      motion in an offset phase pattern. CLINICAL RELEVANCE: This is a valid model for
      measuring the three-dimensional motion of the spine. Normative data were obtained
      to better understand the effects of spine disorders on vertebral motion over the
      gait cycle.

PMID- 24306708
TI  - Whole-exome sequencing: discovering genetic causes of orthopaedic disorders.

PMID- 24306709
TI  - AOA 2013-2014 Presidential address: Failure to succeed?: AOA critical issues.

PMID- 24306710
TI  - Using the arthroscopic surgery skill evaluation tool as a pass-fail examination.
AB  - BACKGROUND: Examination of arthroscopic skill requires evaluation tools that are
      valid and reliable with clear criteria for passing. The Arthroscopic Surgery
      Skill Evaluation Tool was developed as a video-based assessment of technical
      skill with criteria for passing established by a panel of experts. The purpose of
      this study was to test the validity and reliability of the Arthroscopic Surgery
      Skill Evaluation Tool as a pass-fail examination of arthroscopic skill. METHODS:
      Twenty-eight residents and two sports medicine faculty members were recorded
      performing diagnostic knee arthroscopy on a left and right cadaveric specimen in
      our arthroscopic skills laboratory. Procedure videos were evaluated with use of
      the Arthroscopic Surgery Skill Evaluation Tool by two raters blind to subject
      identity. Subjects were considered to pass the Arthroscopic Surgery Skill
      Evaluation Tool when they attained scores of >= 3 on all eight assessment
      domains. RESULTS: The raters agreed on a pass-fail rating for fifty-five of sixty
      videos rated with an interclass correlation coefficient value of 0.83. Ten of
      thirty participants were assigned passing scores by both raters for both
      diagnostic arthroscopies performed in the laboratory. Receiver operating
      characteristic analysis demonstrated that logging more than eighty arthroscopic
      cases or performing more than thirty-five arthroscopic knee cases was predictive
      of attaining a passing Arthroscopic Surgery Skill Evaluation Tool score on both
      procedures performed in the laboratory. CONCLUSIONS: The Arthroscopic Surgery
      Skill Evaluation Tool is valid and reliable as a pass-fail examination of
      diagnostic arthroscopy of the knee in the simulation laboratory. CLINICAL
      RELEVANCE: This study demonstrates that the Arthroscopic Surgery Skill Evaluation
      Tool may be a useful tool for pass-fail examination of diagnostic arthroscopy of
      the knee in the simulation laboratory. Further study is necessary to determine
      whether the Arthroscopic Surgery Skill Evaluation Tool can be used for the
      assessment of multiple arthroscopic procedures and whether it can be used to
      evaluate arthroscopic procedures performed in the operating room.

PMID- 24306711
TI  - Refining the parameters for diagnosis of periprosthetic infection: commentary on
      an article by Christian P. Christensen, MD, et al.: "The natural progression of
      synovial fluid white blood-cell counts and the percentage of polymorphonuclear
      cells after primary total knee arthroplasty. a multicenter study".

PMID- 24306712
TI  - An injectable BMP cocktail for fracture-healing--a study that others have only
      imagined: commentary on an article by Thomas Lyon, MD, et al.: "Efficacy and
      safety of recombinant human bone morphogenetic protein-2/calcium phosphate matrix
      for closed tibial diaphyseal fracture. a double-blind, randomized, controlled
      phase-II/III trial".

PMID- 24306713
TI  - Learning curve for new technology: climbing that hill: commentary on an article
      by Mikko Peltola, MSc, et al.: "Learning curve for new technology? A Nationwide
      register-based study of 46,363 total knee arthroplasties".

PMID- 24306714
TI  - The deficiency of soluble proteins and plastid ribosomal RNA in the albino pollen
      plantlets of rice.
AB  - The components of soluble protein and ribosomal RNA in green and albino pollen
      plantlets of rice were studied by means of polyacrylamide gel electrophoresis.
      The results were as follows: (1) Soluble protein: the soluble proteins in green
      pollen plantlets may be fractionated into 15 bands of varying intensities in
      which the highest content and the most prominent one is band 3 (fraction I
      protein). Band 3, however, is nearly absent in albino pollen plantlets. (2)
      Ribosomal RNA (rRNA): rRNA of high molecular weight in green pollen plantlets may
      be fractionated into 4 bands, i.e. 25S RNA and 18S RNA in cytoplasmic ribosomes,
      and 23S RNA and 16S RNA in plastid ribosomes. Little or no 23S RNA and 16S RNA,
      however, is found in albino pollen plantlets. Together with the evidence obtained
      by other workers, it is suggested that albino forms of pollen plantlets is caused
      by the impairment of DNA. 

PMID- 24306715
TI  - The evaluation of horizontal resistance of winter wheats by the 'center pivot'
      method.
AB  - Twenty bread wheat varieties were sown in forty meter long plots and infected
      with a mixture of three races of stem rust (14, 34, 311) in the Center-pivot
      design. The epidemic's development and its effect on yield (factors) were studied
      in an experiment.With the Center-pivot method we modelled the natural processes
      without chemicals. The epidemic's development and the processes connected with it
      can be studied quantitatively as well as by subjective evaluation.Some of the
      studied genotypes were quickly infected and others slowly. The date of infection
      proved to be especially important to the amount of yield decrease.However, a
      quick spread of the epidemic does not inevitably lead to a decrease of yield and
      1000-grain-weight for every genotype.Vertical resistance has qualitative
      features. On the other hand, there is only a quantitative difference between
      field resistant and tolerant genotypes, and between horizontally resistant and
      susceptible ones. The tolerant genotypes cannot limit the spread of the epidemic,
      but they can limit the degree of damage, and so their yields and 1000-grain
      weights are essentially uninfluenced. The field resistant genotypes slow down the
      epidemic's development, and therefore their yields and 1000-grain-weights
      decrease less. This fact makes possible their separation in two steps, first on
      the basis of epidemic development, and then by measuring the decrease of yield
      and 1000-grainweight.Tolerance and field resistance are supposed to be inherited
      olygenically. Consequently, breeding for horizontal resistance should work with
      basically different methods than those previously used for race-specific
      resistance. 

PMID- 24306716
TI  - Genes in diploid triticinae compensating for the low temperature regulating gene
      Ltp in chromosome 5D of Triticum aestivum.
AB  - Hybrids of Triticum aestivum (monosomic 5D or ditelosomic 5DL) x T. speltoides (=
      Ae. speltoides) showed that the genotype of T. speltoides carries gene(s) which
      can partially compensate for the expected decrease in chromosome association at
      low temperatures (10 degrees C) in the absence of chromosome 5D. In hybrids of T.
      aestivum (normal, ditelosomic 3DL or ditelosomic 3DL-monosomic 5D) x T.
      longissimum (= Ae. sharonensis), this compensation was not observed.In normal F1
      hybrids of T. durum x T. longissimum partial chromosome association occurred at
      10 degrees C and this stabilizer effect may be explained by the presence of a Ltp
      like gene on chromosome 5A. When a line of T. durum carrying a homozygous
      translocated 5B-5D chromosome was used in the crosses an even higher chromosome
      association was observed.These results suggest either the existence of a promoter
      gene for chromosome association in the 5D translocated segment or the loss of a
      weak suppressor gene in the removed segment of 5B. It was concluded that the
      translocated 5D segment did not carry the Ltp stabilizer gene. 

PMID- 24306717
TI  - Environmental maternal influences on body composition in mice selected for body
      weight.
AB  - The effect of the postnatal maternal environment, simulated by rearing mice in
      litters of three, six or nine, on body weight and body composition was
      investigated in three lines of mice differing widely in growth rate. The lines
      were selected for high (H6) and low (L6) 6-week body weight while the control
      line was maintained by random selection. Body weight and weights and percentages
      of ether extract, water, ash and protein at 21, 42, 63 and 84 days were recorded.
      With few exceptions, there were positive correlated responses to selection in
      body weight and in weights of body components. At 21 and 42 days the correlated
      responses were larger in L6 mice than in H6 mice. Body weight and weights of body
      components were larger for mice reared in litters of three than for those reared
      in litters of nine. Also, mice reared in litters of six were intermediate in body
      weight and weights of some of the body components between those reared in litters
      of three and nine. Differences in body weight and weights of body components due
      to postnatal maternal environment were small by comparison with differences due
      to genetic line. There were significant line by maternal environment interactions
      in body weight at 21 days and in ether extract weight at 21 and 63 days. Line and
      maternal environment differences in percentages of body components did not follow
      any consistent trend. The results for percentages of body components were further
      complicated by line x maternal environment interactions. In general, both line
      and postnatal maternal environmental differences in percentages of body
      components diminished with age. 

PMID- 24306718
TI  - The use of matrix specifications in defining gene action in genotypic value
      models and generation mean analysis.
AB  - Gene action and interaction have been defined in the literature by the use of a
      variety of notations (Mather 1949; Hayman 1954, 1955, 1957; Jinks 1954;
      Kempthorne 1954, 1955). This leads to unnecessary complications in understanding
      the subject. This paper provides a simple convenient way of translating one
      parameterization into another and illustrates the simple linear relationship
      between them. The various notations are written in matrix form by the use of a
      specification matrix. This provides a convenient compact method of presentation
      of the relevant Equations. The linear relationship between the genetic parameters
      enables these to be estimated in the most convenient way and then converted to
      other parameters for the purposes of comparison. The generation means Equations
      of Hayman (1958) are derived using the matrix formulation as an illustration of
      the use of the specification matrix. 

PMID- 24306719
TI  - Structural and functional analysis of the scute locus in Drosophila melanogaster.
AB  - The functional expression of 12 scute alleles in homozygotes and compounds of
      Drosophila melanogaster at 14 degrees , 22 degrees , 30 degrees C is analysed.
      Based on the data obtained, linear maps for bristles and mutations are built. The
      basic features of the maps, clustering and polarity, are invariable with respect
      to temperature, scute gene dosage and cross direction. In addition local
      dominance of the norm over bristle reduction was produced by the scute mutation;
      different types of complementation reactions were established for each bristle.
      The gene scute is treated as an operon-like system, composed of 3-4 cistrons with
      each controlling the formation of bristles on a particular region of the fly's
      body. This model argues well with the structure of maps constructed and implies a
      post-translational level of initial events of bristle-formation process. 

PMID- 24306720
TI  - Environmental monitoring of alcohol sulfates and alcohol ethoxysulfates in marine
      sediments.
AB  - The study describes the environmental monitoring of anionic surfactants-alcohol
      sulfates (AS) and alcohol ethoxysulfates (AES)-in marine sediments. Concentration
      values were obtained after pressurised liquid extraction (PLE) and liquid
      chromatography-tandem mass spectrometry analysis (LC-MS/MS). Samples were
      collected from a range of wastewater discharge points along the coast of the
      provinces of Huelva, Malaga, Granada and Almeria. Urban, agricultural and
      industrial wastewaters are discharged at the selected 38 sampling sites.
      Principal component analysis was carried out in order to evaluate the
      distribution and behaviour of these compounds in these coastal environments.
      Evaluation of the data revealed that the behaviour and sources of AS and AES in
      marine sediments are different, and that the distribution of AES depends on the
      length of the alkyl chain, while the number of ethoxylated units is not relevant.
      Additionally, the 38 sampling sites can be grouped into only two types of
      outfalls according to their AS distribution. The concentration of compounds in
      sediment samples ranged from 7.52 to 13.50 mg kg(-1) for AS, from 3.04 to 10.68
      mg kg(-1) for AES-C12Ex and from 3.83 to 11.56 mg kg(-1) for AES-C14Ex.

PMID- 24306721
TI  - Environmental and health risk assessment of Pb, Zn, As and Sb in soccer field
      soils and sediments from mine tailings: solid speciation and bioaccessibility.
AB  - Areas polluted by the persistent presence of metal(loid)s induce health problems,
      especially when recreational activities (on land or water) promote human exposure
      to the pollutants. This study focuses on one of the most encountered worldwide
      mining waste, i.e. those from the extraction of Pb-Zn-Ag. The representative Pb
      Zn-rich tailing (about 64,100 m(3)) sampled is located near a soccer field and a
      famous river for fishing. The scientific interests is relative to: (1) mobility
      and bioaccessibility of metal(oid)s, (2) human risk assessments and (3)
      relationship between human risks and solid-bearing phases in the environment.
      Soccer field soils, tailings and sediments from the nearby river were sampled;
      moreover, metal(loid) speciation (from BCR experiments) and bioaccessibility were
      measured and solid speciation performed by X-ray diffraction and electron
      microscopy in order to highlight metal(loid) dispersion and impact. Results
      demonstrate that the soccer field is highly contaminated by Pb, Zn, As and Sb due
      primarily to waste runoff. In terms of risk assessment, Pb and As human
      bioaccessibility highlights the major health risk (48 and 22.5 % of human
      bioaccessibility, respectively). Since local populations are regularly in close
      contact with metal(loid)s, the health risk due to pollutant exposure needs to be
      reduced through sustainable waste disposal and the rehabilitation of polluted
      sites.

PMID- 24306722
TI  - Sonochemical degradation of a pharmaceutical waste, atenolol, in aqueous medium.
AB  - Atenolol is a beta-blocker drug and an identified emerging pollutant. Advanced
      oxidation processes (AOPs) utilise the reaction of a highly oxidising species
      (hydroxyl radicals, (*)OH) for the mineralisation of emerging pollutants since
      conventional treatment methodologies generally fail to degrade these compounds.
      In the present work, degradation of atenolol was carried out using ultrasound
      with frequencies ranging from 200 kHz to 1 MHz as a source of hydroxyl radical.
      The degradation was monitored by HPLC, total organic carbon (TOC) and chemical
      oxygen demand (COD) reduction and ion chromatography (IC). Nearly 90 % of
      degradation of atenolol was observed with ultrasound having 350 kHz. Both
      frequency and power of ultrasound affect the efficiency of degradation. Nearly
      100 % degradation was obtained at a pH of 4. Presence of various additives such
      as sodium dodecyl sulphate, chloride, sulphate, nitrate, phosphate and
      bicarbonate was found to reduce the efficiency of degradation. Although nearly
      100 % degradation of atenolol was observed under various experimental conditions,
      only about 62 % mineralisation (from TOC and COD measurements) was obtained.
      Nearly eight intermediate products were identified using high-resolution mass
      spectrometry (LC-Q-TOF). These products were understood as the results of
      hydroxyl radical addition to atenolol. The degradation studies were also carried
      out in river water which also showed a similar degradation profile. A mechanism
      of degradation and mineralisation is presented.

PMID- 24306723
TI  - Changes in the nature of dissolved organics during pulp and paper mill wastewater
      treatment: a multivariate statistical study combining data from three analytical
      techniques.
AB  - The paper-making process can produce large amounts of wastewater (WW) with high
      particulate and dissolved organic loads. Generally, in developed countries,
      stringent international regulations for environmental protection require pulp and
      paper mill WW to be treated to reduce the organic load prior to discharge into
      the receiving environment. This can be achieved by primary and secondary
      treatments involving both chemical and biological processes. These processes
      result in complex changes in the nature of the organic material, as some
      components are mineralised and others are transformed. In this study, changes in
      the nature of organics through different stages of secondary treatment of pulp
      and paper mill WW were followed using three advanced characterisation techniques:
      solid-state (13)C nuclear magnetic resonance (NMR) spectroscopy, pyrolysis-gas
      chromatography mass spectrometry (py-GCMS) and high-performance size-exclusion
      chromatography (HPSEC). Each technique provided a different perspective on the
      changes that occurred. To compare the different chemical perspectives in terms of
      the degree of similarity/difference between samples, we employed non-metric
      multidimensional scaling. Results indicate that NMR and HPSEC provided strongly
      correlated perspectives, with 86 % of the discrimination between the organic
      samples common to both techniques. Conversely, py-GCMS was found to provide a
      unique, and thus complementary, perspective.

PMID- 24306724
TI  - Emissions behavior and distribution of polychlorinated dibenzo-p-dioxins and
      furans (PCDD/Fs) from cement kilns in China.
AB  - The production of cement in China is accompanied by various emissions, such as
      fine particulate matter, heavy metals, nitrogen oxides, sulfur oxides, carbon
      dioxide.... Moreover, cement kiln presents a potential health risk to its
      surroundings, linking to emissions of persistent organic pollutants (POPs), such
      as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), in brief
      dioxins. Flue gas samples were collected from five typical cement kilns during
      twelve runs and were used to evaluate the levels and distribution of PCDD/Fs in
      the emissions from cement kilns. The PCDD/Fs concentrations (136 congeners) and I
      TEQ values ranged from 2.3 to >40 ng/m(3) and 9.3~90.8 * 10(-3) ng I-TEQ/m(3),
      respectively, which were lower than the emission standard in China (0.1 ng I
      TEQ/m(3)). In weight units, the dominant congeners were OCDD, 1,2,3,4,6,7,8
      HpCDF, and OCDF; 2,3,4,7,8-PeCDF is the largest contributor (36-66 %) to the
      total I-TEQ value of twelve runs. HxCDF and TCDF were the first two most abundant
      homologue groups (12-85 and 4-52 %), and the homologue concentration decreased
      with rising chlorine number for PCDDs. In addition, there was no marked
      difference in homologue profiles when solid wastes (refuse-derived fuel and
      municipal solid waste) and hazardous wastes (DDT and POPs) were combusted as
      supplemental fuels. The use of various supplemental fuels had no obvious effect
      on the fingerprint of PCDD/F homologues. Moreover, there was no significant
      difference in levels of PCDD/Fs emission due to the diversity of production
      capacity, which were consistent with reported previously. Air pollution control
      device had effect on the homologue profiles, and cement system with electrostatic
      precipitators (ESP) had more fractions of octachloro congeners to the total.

PMID- 24306725
TI  - Occurrence and removal of six pharmaceuticals and personal care products in a
      wastewater treatment plant employing anaerobic/anoxic/aerobic and UV processes in
      Shanghai, China.
AB  - The occurrence and removal of six pharmaceuticals and personal care products
      (PPCPs) including caffeine (CF), N, N-diethyl-meta-toluamide (DEET),
      carbamazepine, metoprolol, trimethoprim (TMP), and sulpiride in a municipal
      wastewater treatment plant (WWTP) in Shanghai, China were studied in January
      2013; besides, grab samples of the influent were also taken every 6 h, to
      investigate the daily fluctuation of the wastewater influent. The results showed
      the concentrations of the investigated PPCPs ranged from 17 to 11,400 ng/L in the
      WWTP. A low variability of the PPCP concentrations in the wastewater influent
      throughout the day was observed, with the relative standard deviations less than
      25 % for most samples. However, for TMP and CF, the slight daily fluctuation
      still reflected their consumption patterns. All the target compounds except CF
      and DEET, exhibited poor removal efficiencies (<40 %) by biological treatment
      process, probably due to the low temperature in the bioreactor, which was
      unfavorable for activated sludge. While for the two biodegradable PPCPs, CF, and
      DEET, the anaerobic and oxic tank made contributions to their removal while the
      anoxic tank had a negative effect to their elimination. The tertiary UV treatment
      removed the investigated PPCPs by 5-38 %, representing a crucial polishing step
      to compensate for the poor removal by the biologic treatment process in winter.

PMID- 24306726
TI  - Impact of haze and air pollution-related hazards on hospital admissions in
      Guangzhou, China.
AB  - Guangzhou is a metropolitan in south China with unique pollutants and geographic
      location. Unlike those in western countries and the rest of China, the appearance
      of haze in Guangzhou is often (about 278 days per year on average of 4 years).
      Little is known about the influence of these hazes on health. In this study, we
      investigated whether short-term exposures to haze and air pollution are
      associated with hospital admissions in Guangzhou. The relationships between haze,
      air pollution, and daily hospital admissions during 2008-2011 were assessed using
      generalized additive model. Studies were categorized by gender, age, season, lag,
      and disease category. In haze episodes, an increase in air pollutant emissions
      corresponded to 3.46 (95 % CI, 1.67, 5.27) increase in excessive risk (ER) of
      total hospital admissions at lag 1, 11.42 (95 % CI, 4.32, 18.99) and 11.57 (95 %
      CI, 4.38, 19.26) increases in ERs of cardiovascular illnesses at lags 2 and 4
      days, respectively. As to total hospital admissions, an increase in NO2 was
      associated with a 0.73 (95 % CI, 0.11, 1.35) and a 0.28 (95 % CI, 0.11, 0.46)
      increases in ERs at lag 5 and lag 05, respectively. For respiratory illnesses,
      increases in NO2 was associated with a 1.94 (95 % CI, 0.50, 3.40) increase in ER
      at lag 0, especially among chronic obstructive pulmonary disease. Haze (at lag1)
      and air pollution (for NO2 at lag 5 and for SO2 at lag3) both presented more
      drastic effects on the 19 to 64 years old and in the females. Together, we
      demonstrated that haze pollution was associated with total and cardiovascular
      illnesses. NO2 was the sole pollutant with the largest risk of hospital
      admissions for total and respiratory diseases in both single- and multi-pollutant
      models.

PMID- 24306727
TI  - Tributyltin (TBT) induces oxidative stress and modifies lipid profile in the
      filamentous fungus Cunninghamella elegans.
AB  - To investigate the response of the tributyltin-degrading fungal strain
      Cunninghamella elegans to the organotin, a comparative lipidomics strategy was
      employed using an LC/MS-MS technique. A total of 49 lipid species were
      identified. Individual phospholipids were then quantified using a multiple
      reaction monitoring method. Tributyltin (TBT) caused a decline in the amounts of
      many molecular species of phosphatidylethanolamine or phosphatidylserine and an
      increase in the levels of phosphatidic acid, phosphatidylinositol and
      phosphatidylcholine. In the presence of TBT, it was observed that overall
      unsaturation was lower than in the control. Lipidome data were analyzed using
      principal component analysis, which confirmed the compositional changes in
      membrane lipids in response to TBT. Additionally, treatment of fungal biomass
      with butyltin led to a significant increase in lipid peroxidation. It is
      suggested that modification of the phospholipids profile and lipids peroxidation
      may reflect damage to mycelium caused by TBT. 

PMID- 24306728
TI  - Assessment of the contribution of sewer deposits to suspended solids loads in
      combined sewer systems during rain events.
AB  - Within the French observatories network SOERE "URBIS," databases of continuous
      turbidity measurements accumulating hundreds of events and many dry weather days
      are available for two sites with different features (Clichy in Paris and Ecully
      in Lyon). These measurements, converted into total suspended solids (TSS)
      concentration using TSS-turbidity relationships and combined with a model of
      runoff event mean concentration, enable the assessment of the contribution of
      sewer deposits to wet weather TSS loads observed at the outlet of the two
      watersheds. Results show that the contribution of sewer deposits to wet weather
      suspended solid's discharges is important but variable (between 20 and 80 % of
      the mass at the outlet depending on the event), including a site allegedly free
      of (coarse) sewer deposits. The uncertainties associated to these results are
      assessed too. 

PMID- 24306729
TI  - Echocardiography of the pulmonary circulation and right ventricular function:
      exploring the physiologic spectrum in 1,480 normal subjects.
AB  - BACKGROUND: Although transthoracic echocardiography (TTE) is an excellent
      noninvasive screening test for pulmonary hypertension, the physiologic range of
      Doppler echocardiography-derived pulmonary pressures remains not completely
      investigated. The aim of the present study was, therefore, to explore the full
      spectrum of pulmonary pressures and right ventricular (RV) functional indexes by
      TTE in healthy subjects and to investigate clinical and echocardiographic
      correlates. METHODS: A random sample of 1,480 healthy individuals (mean age, 36.1
      +/- 15.5 years; range, 20-80 years; 905 men) underwent a comprehensive TTE.
      Pulmonary artery systolic pressure (PASP), mean pressure, and pulmonary vascular
      resistance were estimated by standard Doppler echocardiography formulas. In
      addition, RV diastolic (Doppler transtricuspid inflow measurements) and systolic
      indexes (RV fractional area change, RV tissue Doppler peak systolic velocity,
      tricuspid annular plane systolic excursion) were calculated. RESULTS: PASP and
      mean pulmonary artery pressure values were significantly higher in subjects aged
      > 50 years and in those with a BMI > 30 kg/m2. In particular, a PASP > 40 mm Hg
      was found in 118 subjects (8%) of those aged > 50 years and in 103 (7%) of those
      with a BMI > 30 kg/m2. No differences by age were registered in RV systolic
      indexes and in pulmonary vascular resistances. On multivariate analysis, in the
      overall study population, age, BMI, mitral E/e' ratio, and left ventricular
      stroke volume were the only independent predictors of PASP. CONCLUSIONS: This
      study delineates an estimate of pulmonary hemodynamics in a wide age range cohort
      of healthy subjects. Pulmonary pressures increased with age and BMI, as expected.

PMID- 24306730
TI  - Medical, cognitive and academic outcomes of very low birth weight infants at age
      10-14 years in Ireland.
AB  - BACKGROUND: Low birth weight (LBW) is a leading cause of infant mortality and
      morbidity, and a specific risk for the development of neuro-developmental and
      academic problems. AIM: To examine the medical, cognitive and academic outcomes
      of VLBW (<1,500 g) children, born in one maternity hospital in Dublin between
      1995 and 1997. METHODS: The study employed a prospective/cohort design, with semi
      structured, and standardised measures, along with the completion of a study
      specific questionnaire. Ratings were obtained from parents and teachers. RESULTS:
      Of the 127 surviving VLBW cohort, 64 (50 %) consented to assessment at a mean age
      of 11.6 years (SD 1.0) along with a matched-weight and gender control sample of
      51. VLBW children had an increased risk of chronic medical problems and neuro
      sensory deficits, but without any increased use in services. Similarly, they had
      lower IQ (mean 89.7 compared to NBW 101.3, p < 0.001) and more were identified by
      teachers to have special education needs (33 % VLBW vs. 7 % NBW, p < 0.005). With
      regard to academic attainments, birth weight had a significant [t(98) = -4.54, p
      < 0.001] and robust effect (eta(2) = 0.17) on mathematical attainment scores.
      Those with lower SES fared least well off. CONCLUSIONS: Although significant
      advances have been made in reducing infant mortality, there is a recognised
      increased risk of subsequent disability especially with decreasing gestational
      age, and when coupled with low SES. Having facilitated the survival of vulnerable
      infants, services must be available for the necessary on-going medical and
      educational support and treatment that they require throughout adolescent years.

PMID- 24306732
TI  - [Choroidal thickness after scleral buckling surgery in macula-off rhegmatogenous
      retinal detachment].
AB  - BACKGROUND: Enhanced depth imaging (EDI) optical coherence tomography (OCT)
      provides high-definition cross-sectional images of the choroid. Information on
      alterations in choroidal thickness (CT) after scleral buckling surgery (SBS) is
      rare. PATIENTS AND METHODS: The medical charts of 122 patients (122 eyes) who
      underwent SBS for macula-off rhegmatogenous retinal detachment (RRD) were
      retrospectively analyzed. Patients with a follow-up >= 6 months were included.
      Postoperative EDI-OCT images concerning CT were evaluated 1 week, 1 month and 6
      months postoperatively in 4 groups: group 1 cerclage + cryopexy (n = 39 eyes),
      group 2 cerclage + cryopexy + sponge (n = 28 eyes), group 3 SBS + subretinal
      fluid drainage (SRD) (n = 25 eyes) and group 4 SBS + sponge + SRD (n = 30 eyes).
      Subfoveal CT was compared between the groups and with the non-operated fellow
      eye. RESULTS: Subfoveal CT in groups 1, 2, 3 and 4 was thicker 1 week
      postoperatively. There were no significant differences between the groups or when
      comparing the operated eye with the fellow eye 1 and 6 months postoperatively.
      CONCLUSION: There were no differences in subfoveal CT 1 and 6 months after SBS
      between the eye with macula-off RRD and the fellow eye. The use of a sponge or
      SRD induced no differences concerning subfoveal CT.

PMID- 24306733
TI  - Analysis of an automated background correction method for cardiovascular MR phase
      contrast imaging in children and young adults.
AB  - BACKGROUND: Phase contrast magnetic resonance imaging (MRI) is a powerful tool
      for evaluating vessel blood flow. Inherent errors in acquisition, such as phase
      offset, eddy currents and gradient field effects, can cause significant
      inaccuracies in flow parameters. These errors can be rectified with the use of
      background correction software. OBJECTIVE: To evaluate the performance of an
      automated phase contrast MRI background phase correction method in children and
      young adults undergoing cardiac MR imaging. MATERIALS AND METHODS: We conducted a
      retrospective review of patients undergoing routine clinical cardiac MRI
      including phase contrast MRI for flow quantification in the aorta (Ao) and main
      pulmonary artery (MPA). When phase contrast MRI of the right and left pulmonary
      arteries was also performed, these data were included. We excluded patients with
      known shunts and metallic implants causing visible MRI artifact and those with
      more than mild to moderate aortic or pulmonary stenosis. Phase contrast MRI of
      the Ao, mid MPA, proximal right pulmonary artery (RPA) and left pulmonary artery
      (LPA) using 2-D gradient echo Fast Low Angle SHot (FLASH) imaging was acquired
      during normal respiration with retrospective cardiac gating. Standard phase image
      reconstruction and the automatic spatially dependent background-phase-corrected
      reconstruction were performed on each phase contrast MRI dataset. Non-background
      corrected and background-phase-corrected net flow, forward flow, regurgitant
      volume, regurgitant fraction, and vessel cardiac output were recorded for each
      vessel. We compared standard non-background-corrected and background-phase
      corrected mean flow values for the Ao and MPA. The ratio of pulmonary to systemic
      blood flow (Qp:Qs) was calculated for the standard non-background and background
      phase-corrected data and these values were compared to each other and for
      proximity to 1. In a subset of patients who also underwent phase contrast MRI of
      the MPA, RPA, and LPA a comparison was made between standard non-background
      corrected and background-phase-corrected mean combined flow in the branch
      pulmonary arteries and MPA flow. All comparisons were performed using the
      Wilcoxon sign rank test (alpha = 0.05). RESULTS: Eighty-five children and young
      adults (mean age 14 years; range 10 days to 32 years) met the criteria for
      inclusion. Background-phase-corrected mean flow values for the Ao and MPA were
      significantly lower than those for non-background-corrected standard Ao (P =
      0.0004) and MPA flow values (P < 0.0001), respectively. However, no significant
      difference was seen between the standard non-background (P = 0.295) or background
      phase-corrected (P = 0.0653) mean Ao and MPA flow values. Neither the mean
      standard non-background-corrected (P = 0.408) nor the background-phase-corrected
      (P = 0.0684) Qp:Qs was significantly different from 1. However in the 27 patients
      with standard non-background-corrected data, the difference between the Ao and
      MPA flow values was greater than 10%. There were 19 patients with background
      phase-corrected data in which the difference between the Ao and MPA flow values
      was greater than 10%. In the subset of 43 patients who underwent MPA and branch
      pulmonary artery phase contrast MRI, the sum of the standard non-background
      corrected mean RPA and LPA flow values was significantly different from the
      standard non-background-corrected mean MPA flow (P = 0.0337). The sum of the
      background-phase-corrected mean RPA and LPA flow values was not significantly
      different from the background-phase-corrected mean MPA flow value (P = 0.1328),
      suggesting improvement in pulmonary artery flow calculations using background
      phase-correction. CONCLUSION: Our data suggest that background phase correction
      of phase contrast MRI data does not significantly change Qp:Qs quantification,
      and there are residual errors in expected Qp:Qs quantification despite background
      phase correction. However the use of background phase correction does improve
      quantification of MPA flow relative to combined RPA and LPA flow. Further work is
      needed to validate these findings in other patient populations, using other MRI
      units, and across vendors.

PMID- 24306734
TI  - Aneurysmal dilatation of persistent vitelline vein with thrombus in a neonate.
AB  - The paired vitelline veins selectively involute and form a part of the portal
      vein during embryonic development. The presence of a persistent vitelline vein
      segment after birth is very rare and can be confused with anomalies of the portal
      and umbilical veins. We present sonographic, CT and MRI findings of aneurysmal
      dilatation of a persistent vitelline vein with thrombus in a neonate; this case
      was first misdiagnosed as an umbilical vein varix by prenatal US. MRI was used to
      identify the persistent vitelline vein segment and the remnant umbilical vein
      segment. 

PMID- 24306735
TI  - Utility of sonographic assessment of the position of the third part of the
      duodenum using water instillation in intestinal malrotation: a single-center
      retrospective audit.
AB  - BACKGROUND: Intestinal malrotation and particularly volvulus are potentially
      devastating conditions. Upper gastrointestinal (UGI) contrast studies have been
      considered the gold standard for diagnosis. However the use of ultrasonography
      (US) has been increasingly described. We describe a method for delineating the
      duodenal anatomy with US as a means to exclude malrotation. OBJECTIVE: To report
      our experience using US to assess intestinal rotation. MATERIALS AND METHODS: We
      conducted a retrospective audit of US scans performed at a tertiary referral
      centre to exclude malrotation for paediatric surgery between 2008 and 2011.
      RESULTS: One hundred thirty-nine infants were included, of whom 114 had a normal
      US scan. Of the 114, nine had subsequent upper gastrointestinal contrast studies
      that confirmed the initial results; there were no false-negatives. There were
      abnormal US scans in four infants associated with midgut volvulus and
      malrotation; there were no false-positives. The other 21 US scans were equivocal,
      and 11 of these had a confirmatory UGI contrast study; only one required surgery
      to correct malrotation. CONCLUSION: US has been a safe and effective tool in the
      assessment of intestinal rotation at our institution. The main advantages of US
      imaging are its lack of ionising radiation and its rapid and accurate diagnosis
      of volvulus.

PMID- 24306737
TI  - Impact of parental holocaust traumatization on offsprings' reports of parental
      child-rearing practices.
AB  - The impact of severe parental traumatization on child rearing was investigated in
      a nonselective nonclinical group of Israeli adolescents, offspring of Holocaust
      survivors (N=76). Adolescents' reports of parental behavior were correlated with
      a measure of severity of parental Holocaust traumatization. For boys, the
      severity of paternal traumatization (PT) correlated negatively with reported
      child-rearing practices denoting both paternal nurturance and paternal control.
      Mothers were perceived by boys as withholding nurturance and exerting hostile
      control as a function of their spouses' degree of traumatization (PT). Females
      perceived fathers as being inconsistent socializers, with anxiety-provoking and
      enforcement overtones as a function of PT. PT is, however, uncorrelated with any
      maternal practices as reported by girls. The severity of maternal traumatization
      (MT) was correlated with fathers' refrainment with girls from harsh modes, such
      as control, hostile control, and instilling anxiety. MT correlated for boys with
      maternal refrainment from harsh child-rearing practices, such as hostile control
      and enforcement. The results clearly point to the existence of significant
      associations between degree of parental traumatization and reported child-rearing
      experiences. The pattern of correlations indicate specific intragender and
      intergender transgenerational interactions. 

PMID- 24306738
TI  - Dimensions of the self-concept: A source of further distinctions in the nature of
      self-consciousness.
AB  - This study distinguished between forms of self-consciousness (private self
      consciousness and social anxiety) and investigated the effect of self-esteem,
      vulnerability to criticism, and the tendency to fantasize on each. Utilizing a
      sample of adolescents (age 12 to 19 years), a structural equation analysis using
      unobserved variables revealed that, as expected, vulnerability to others'
      criticism heightened both private self-consciousness and social anxiety. In
      contrast, the tendency to fantasize in everyday life increased only private self
      consciousness, and low self-esteem led directly only to increased social anxiety.
      Further, results showed that self-esteem had an appreciable indirect effect on
      both private self-consciousness and social anxiety, as mediated by vulnerability
      and the tendency to fantasize, indicating that the effect of self-esteem (a
      primary motivator) was more complex than an analysis of direct effects would
      indicate. Implications for our understanding of self-consciousness and the self
      concept are discussed. 

PMID- 24306739
TI  - Adolescent alcohol abuse and other problem behaviors: Their relationships and
      common parental influences.
AB  - This study was designed to explore the relationships between adolescent alcohol
      abuse and other problem behaviors. Parental socialization practices, particularly
      support/nurturance, were also examined for common influences on both alcohol
      abuse and other youthful deviance. Interviews were conducted with a
      representative household sample of adolescents aged 12-17 years and their
      parents. The findings support the theory that adolescent alcohol abuse is part of
      a complex psychosocial problem behavior syndrome and that a high degree of
      parental nurturance may be a significant deterrence to alcohol abuse and more
      general deviant behaviors. 

PMID- 24306740
TI  - Family structure, family attributes, and delinquency in a sample of low-income,
      minority males and females.
AB  - A popular thesis in criminology links "broken homes" to juvenile delinquency.
      This thesis has been invoked to explain higher rates of delinquency among youth
      from low-income, minority families than among youth from mainstream backgrounds.
      The study reported here employs data collected at two points in time to assess
      the thesis that family structure is significantly associated with self-reported
      delinquency within a sample of black males and females from low-income families.
      The relationships between an array of family variables, including family
      structure, and each of four types of self-reported delinquency are examined in
      analysis conducted separately for males and females. Findings indicate that few
      family factors are significant for delinquency and family structure is of minimal
      importance for the types of delinquency examined. The results differ for males
      and females. These findings raise serious questions about the cogency of the
      broken-home thesis of delinquency to explain delinquency among nonmainstream
      groups in our society. 

PMID- 24306741
TI  - Is increased UV-B a threat to crop photosynthesis and productivity?
AB  - It has been suggested that increases in ground-level UV-B, as a result of
      stratospheric ozone depletion, may have major deleterious effects on crop
      photosynthesis and productivity. The direct consequences of such effects have
      been projected by some as a world-wide decrease in crop yields of 20-25%. Further
      losses, or unrealized gains, have also been suggested as a result of increased UV
      B counteracting the beneficial effects of elevated atmospheric CO2. Deleterious
      UV-B effects may be largely partitioned between damage to the plant genome and
      damage to the photosynthetic machinery. Direct damage to DNA is a common result
      of absorption of high energy UV-B photons. However, most plants possess repair
      mechanisms adequate to deal with the levels of damage expected from projected
      increases in ground-level UV-B. In addition, most plants have the ability to
      increase production of UV-absorbing compounds in their leaves as a result of
      exposure to UV-B, UV-A and visible radiation. These compounds contribute
      substantially to reducing UV-B damage in situ. It has also been shown that in
      some plants, under the proper conditions, almost every facet of the
      photosynthetic machinery can be damaged directly by very high UV-B exposures.
      However, electron transport, mediated by Photosystem II (PS II) appears to be the
      most sensitive part of the system. Various laboratories have reported damage to
      virtually all parts of the PS II complex from the Mn binding site to the
      plastoquinone acceptor sites on the opposite surface of the thylakoid membrane.
      However, a critical review of the literature with emphasis on exposure protocols
      and characterization of the radiation environment, revealed that most growth
      chamber and greenhouse experiments and very many field experiments have been
      conducted at unrealistic or indeterminate UV-B exposure levels, especially with
      regard to the spectral balance of their normal radiation environment. Thus, these
      experiments have led directly to large overestimates of the potential for damage
      to crop photosynthesis and yield within the context of 100 year projections for
      stratospheric ozone depletion. Indeed, given the massive UV-B exposures necessary
      to produce many of these effects, we suggest it is unlikely that they would occur
      in a natural setting and urge reconsideration of the purported impacts of
      projected increases of UV-B on crop productivity. 

PMID- 24306742
TI  - In situ evidence that chilling in the light does not cause uncoupling of
      photophosphorylation or detachment of coupling factor in chilling-sensitive
      plants.
AB  - The potential involvement of impaired photophosphorylation in the chilling
      sensitivity of photosynthesis in warm climate plant species has been a topic of
      investigation for more than two decades. With recent advances in the analysis of
      photosynthetic energy transduction in intact leaves, experiments are now possible
      that either address or avoid important uncertainties in the significance and
      interpretation of earlier in vitro work. Nevertheless, different laboratories
      using different techniques to analyze the effects of chilling in the light on
      photophosphorylation in intact cucumber (Cucumis sativus) leaves have come to
      very different conclusions regarding the role of impaired ATP formation capacity
      in the inhibition of net photosynthesis. In order to evaluate these discrepancies
      and bring this issue to a final resolution, in this investigation, we have made a
      detailed analysis of the decay of the flash-induced electrochromic shift and
      changes in chlorophyll fluorescence yield in cucumber leaves before, during and
      after a 5 h light-chill at chill temperatures of between 4 and 10 degrees C. We
      feel that our findings address the major discrepancies in both data and
      interpretation as well as provide convincing evidence that photophosphorylation
      is not disrupted in cucumber leaves during or after light and chilling exposure.
      It follows that impaired photophosphorylation is not a contributing element to
      the inhibition of net photosynthesis that is widely observed in warm climate
      plants as a result of chilling in the light. 

PMID- 24306743
TI  - Spectroscopic studies of bound cytochrome c and an iron-sulfur center in a
      purified reaction center complex from the green sulfur bacterium Chlorobium
      tepidum.
AB  - Flash-induced optical kinetics at room temperature of cytochrome (Cyt) c 551 and
      an Fe-S center (CFA/CFB) bound to a purified reaction center (RC) complex from
      the green sulfur photosynthetic bacterium Chlorobium tepidum were studied. At 551
      nm, the flash-induced absorbance change decayed with a t 1/2 of several hundred
      ms, and the decay was accelerated by 1-methoxy-5-methylphenazinium methyl sulfate
      (mPMS). In the blue region, the absorbance change was composed of mPMS-dependent
      (Cyt) and mPMS-independent component (CFA/CFB) which decayed with a t 1/2 of ~400
      650 ms. Decay of the latter was effectively accelerated by benzyl viologen (Em 
      360 mV) and methyl viologen (-440 mV), and less effectively by triquat (-540 mV).
      The difference spectrum of Cyt c had negative peaks at 551, ~520 and ~420 nm,
      with a positive rise at ~440 to ~500 nm. The difference spectrum of CFA/CFB
      resembled P430 of PSI, and had a broad negative peak at 430~435 nm. 

PMID- 24306744
TI  - Formation of the isocyclic ring of chlorophyll by isolated Chlamydomonas
      reinhardtii chloroplasts.
AB  - Chlamydomonas reinhardtii chloroplasts catalyzed two sequential steps of Chl
      biosynthesis, S-adenosyl-L-methionine:Mg-protoporphyrin IX methyltransferase and
      Mg-protoporphyrin IX monomethyl ester oxidative cyclase. A double mutant strain
      of C. reinhardtii was constructed which has a cell wall deficiency and is unable
      to form chlorophyll in the dark. Dark-grown cells were disrupted with a BioNeb
      nebulizer under conditions which lysed the plasma membrane but not the
      chloroplast envelope. Chloroplasts were purified by Percoll density gradient
      centrifugation. The purified chloroplasts were used to define components required
      for the biosynthesis of Mg-2,4-divinylpheoporphyrin a 5 (divinyl
      protochlorophyllide) from Mg-protoporphyrin IX. Product formation requires the
      addition of Mg-protoporphyrin IX, the substrate for S-adenosyl-L-methionine:Mg
      protoporphyrin IX methyltransferase which produces Mg-protoporphyrin IX
      monomethyl ester. The Mg-protoporphyrin IX monomethyl ester that is generated in
      situ is the substrate for Mg-protoporphyrin IX monomethyl ester oxidative
      cyclase. The reaction product was identified as Mg-2,4-divinylpheoporphyrin a 5
      (divinyl protochlorophyllide) by excitation and emission spectrofluorometry and
      HPLC on ion-paired reverse-phase and polyethylene columns. Mg-2,4
      divinylpheoporphyrin a 5 formation by the coupled enzyme system required O2 and
      was stimulated by the addition of NADP(+), an NADPH regenerating system, and S
      adenosyl-L-methionine. Product was formed at a relatively steady rate for at
      least 60 min. 

PMID- 24306745
TI  - The NADP-linked glyceraldehyde-3-phosphate dehydrogenases of Anabaena variabilis
      and Synechocystis PCC 6803, which lack one of the cysteines found in the higher
      plant enzyme, are not reductively activated.
AB  - Light activation of NADP-linked glyceraldehyde-3-P dehydrogenase involves
      reductive cleavage of a disulfide bond. We have proposed that the inactivating
      disulfide locks the two domains of the enzyme, preventing catalysis, and we have
      tentatively identified the two critical cysteine residues in the chloroplast
      enzyme (D. Li, F.J. Stevens, M. Schiffer and L.E. Anderson (1994) Biophys J. 67:
      29-35). We reasoned that if activation of this enzyme involves these cysteines
      that enzymes lacking one or both should be active in the dark and insensitive to
      reductants. One of these cysteines is present in the enzymes from Anabaena
      variabilis and Synechocystis PCC 6803 but the other is not. Consistent with the
      proposed mechanism, glyceraldehyde-3-P dehydrogenase is not affected by DTT
      treatment in extracts of either of these cyanobacteria. Fructosebisphosphatase is
      DTT-activated in extracts of both of these cyanobacteria and glucose-6-P
      dehydrogenase is inactivated in Synechocystis, as in higher plant chloroplasts.
      Apparently reductive modulation is possible in these cyanobacteria but
      glyceraldehyde-3-P dehydrogenase is not light activated. 

PMID- 24306746
TI  - Polyphasic rise of chlorophyll a fluorescence in herbicide-resistant D1 mutants
      of Chlamydomonas reinardtii.
AB  - Chlorophyll (Chl) a fluorescence transient, a sensitive and non-invasive probe of
      the kinetics and heterogeneity of the filling up of the electron acceptor pool of
      Photosystem II (PS II), was used to characterize D1-mutants of Chlamydomonas
      reinhardtii. Using a shutter-less system (Plant Efficiency Analyzer, Hansatech,
      UK), which provides the first measured data point at 10 MUs and allows data
      accumulation over several orders of magnitude of time, we have characterized, for
      the first time, complete Chl a fluorescence transients of wild type (WT), cell
      wall less (CW-15) C. reinhardtii and several herbicide-resistant mutants of the
      D1 proteins: D1-V219I The mutants are labeled as follows: the single letter code
      for the wild type amino acid, followed by the residue number, then the code for
      the mutated amino acid. A251V, F255Y, S264A G256D and L275F. In all cases, the
      Chl a fluorescence induction transients follow a pattern of O-J-I-P where J and I
      appear as two steps between the minimum Fo (O) and the maximum Fmax (Fm, P)
      levels. The differences among the mutants are in the kinetics of the filling up
      of the electron acceptor pool of PS II (this paper) in addition to those in the
      re-oxidation kinetics of QA (-) to QA, published elsewhere (Govindjee et al.
      (1992) Biochim Biophys. Acta: 1101: 353-358; Strasser et al. (1992) Archs. Sci.
      Geneve 42: 207-224) and not in the ratio of the maximal fluorescence Fm to the
      initial fluorescence Fo. The value of this experimental ratio is Fm/Fo = 4.4+/
      0.21 independent of the mutation. At 600 W m(-2) of 650 nm excitation, distinct
      hierarchy in the fraction of variable Chl a fluorescence at the J level is
      observed: S264A > A251V ~ G256A > L275F ~ V219I > F255Y ~ CW-15 ~ WT. At 300 and
      60 W m(-2) excitation, a somewhat similar hierarchy among the mutants was
      observed for the intermediate levels J and I. Addition of bicarbonate-reversible
      inhibitor formate did not change the O to J phases, slowed the I to P rise, and
      in many cases, slowed the decay of fluorescence beyond the P level. These
      observations are interpreted in terms of formate effect being on the acceptor
      rather than on the donor side (S-states) of PS II. The formate effect was
      different in different mutants, with L275F being the most insensitive mutant
      followed by others (V219I, F255Y, WT, A251V and S264A). Further, in the presence
      of high concentrations of DCMU, identical transients were observed for all the
      mutants and the WT.The quantum yield of photochemistry of PS II, calculated from
      1-(Fo/Fm), is in the range of 0.73 to 0.82 for the WT as well as for the mutants
      examined. Thus, in contrast to differences in the kinetics of the electron
      acceptor side of PS II, there were no significant differences in the maximum
      quantum yield of PS II, among the mutants tested. We suggest that earlier
      photochemistry yield values were much lower (0.4-0.6) than those reported here
      due to either higher measured values of Fo by instruments using camera shutters,
      or due to the use of cells grown in less than-optimal conditions. 

PMID- 24306747
TI  - A mutation in the small subunit of ribulose-1,5-bisphosphate
      carboxylase/oxygenase that reduces the rate of its incorporation into holoenzyme.
AB  - A mutant of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco), in which Arg53 is replaced by Glu, was synthesized and imported into
      isolated chloroplasts. The mutant protein was efficiently imported into the
      chloroplast and correctly processed to the mature size. Like the wild type
      protein, it was stable over a period of at least 2 h. Unlike the wilk-type
      protein however, most of the mutant protein was not assembled with holo-Rubisco
      at the end of a 10-min import reaction. It migrated instead as a diffused band on
      a non-denaturing gel, slower than the precursor protein, but faster than the
      holoenzyme. The level of the unassembled mutant protein in the stroma decreased
      with time, while its level in the assembled fraction has increased, indicating
      that this protein is a slowly-assembled, rather than a non-assembled, mutant of
      the small suubunit of Rubisco. Accumulation of the mutant protein in the
      holoenzyme fraction was dependent on ATP and light. The transient species,
      migrating faster than the holoenzyme but slower than the precursor protein, may
      represent an intermediate in the assembly process of the small subunit of
      Rubisco. 

PMID- 24306748
TI  - Description of energy migration and trapping in photosystem I by a model with two
      distance scaling parameters.
AB  - The energy transfer and trapping kinetics in the core antenna of Photosystem I
      are described in a new model in which the distance between the core antenna
      chlorophylls and P700 is proposed to be considerably longer than the distance
      between the chlorophylls within the antenna. Structurally, the model describes
      the Photosystem I core antenna as a regular sphere around P700, while
      energetically it consists of three levels representing the bulk antenna, P700 and
      the red-shifted antenna pigments absorbing at longer wavelength than P700,
      respectively. It is shown that the model explains experimental results obtained
      from the Photosystem I complex of the cyanobacterium Synechococcus sp. (A.R.
      Holzwarth, G. Schatz, H Brock, and E. Bittersman (1993) Biophys. J. 64: 1813
      1826) quite well, and that no unrealistic charge separation rate and organization
      of the long-wavelength pigments has to be assumed. We suggest that excitation
      energy transfer and trapping in Photosystem I should be described as a 'transfer
      to-the-trap'-limited process. 

PMID- 24306749
TI  - Evolution of PS IIalpha and PS IIbeta centers during the greening of Euglena
      gracilis Z: Correlations with changes in lipid content.
AB  - The building up of the two types of reaction centers, PS IIalpha and PS IIbeta,
      was investigated during the greening of Euglena gracilis Z cells in resting
      medium. The maximal values in the proportion of PS IIalpha centers (55%) and in
      the oxygen evolved per chlorophyll were reached at the outbreak of greening, when
      accumulation of galactolipids (MGDG and DGDG) rich in unsaturated fatty acids
      occurred, and when anionic lipids (SQDG and PG) emerged. As the greening
      progressed, the chlorophyll accumulation corresponded to a secondary enrichment
      in PS IIbeta centers, which built up more rapidly than PS IIalpha centers;
      correlatively, a general saturation of the fatty acids constitutive of all lipid
      classes took place. 

PMID- 24306750
TI  - Isolation and characterisation of the Photosystem two reaction centre complex
      from a double mutant of Chlamydomonas reinhardtii.
AB  - A rapid procedure has been developed for the isolation of the photosystem two
      reaction centre complex (PS II RC) from a double mutant of Chlamydomonas
      reinhardtii, F54-14, which lacks the Photosystem one complex and the chloroplast
      ATPase. Thylakoid membranes are solubilised with 1.5% (w/v) Triton X-100 and the
      PS II RC purified by anion-exchange chromatography using TSK DEAE-650(S) (Merck).
      The complex has a pigment stoichiometry of approximately six chlorophyll a: two
      pheophytin a: one cytochrome b-559: one to two beta-carotene. It photoaccumulates
      reduced pheophytin and oxidised P680 in the presence of sodium dithionite and
      silicomolybdate, respectively. Immunoblotting experiments have confirmed the
      presence of the D1 and D2 polypeptides in this complex. The alpha-subunit of
      cytochrome b-559 was identified by N-terminal sequencing. Comparison of the
      complex with the PS II RC from pea using SDS-polyacrylamide gel electrophoresis
      showed that their polypeptide compositions were similar. However, the alpha
      subunit of cytochrome b-559 from C. reinhardtii has a lower apparent molecular
      weight than the pea counterpart whereas the beta-subunit is larger. 

PMID- 24306752
TI  - Emersonian therapy.

PMID- 24306751
TI  - Corrigendum.

PMID- 24306753
TI  - Eros and wholeness.
AB  - It is suggested that the direction for resolving the current normative confusion
      regarding the place of sexuality in our lives lies in understanding it as a
      manifestation of Eros. Eros is revealed to be the desire for wholeness. In order
      for Eros to achieve its aim, therefore, we must respect the whole fabric of life.
      This respect is manifest when the connections between Eros and six different
      facets of life are held intact and thereby enhanced. These six facets are (1)
      pleasure, (2) human relationship, (3) procreation, (4) family, (5) psychological
      growth, and (6) spiritual growth. The nature of each of these connections is
      briefly discussed. 

PMID- 24306754
TI  - The anthropology of Carl Jung: Implications for pastoral care.
AB  - This article examines the basic tenets of Carl Jung's anthropology, including
      intrapsychic structure, relationships, society, and the process of individuation.
      It then turns to his ideas about God and religion. Jung builds his understanding
      of God from his work in psychology, and because of that method, there are several
      major problems with his theologizing. Nevertheless, his insights are extremely
      valuable to the field of pastoral care, and ministers would do very well to
      appreciate his contribution, though always with a critical eye to its limitation.

PMID- 24306755
TI  - Dramatic religious conversion and schizophrenic decompensation.
AB  - The similarities between dramatic religious and psychotic experiences have long
      been observed and, just as long, have proved a source of confusion and
      misunderstanding. Recent surveys on decompensation to schizophrenic psychosis
      offer not only striking comparisons to the phenomenon of sudden and dramatic
      religious conversion but clues to the limits of continuity between these two
      mental processes. Using Docherty and his associates model of the stages of onset
      of schizophrenic psychosis and their own review of the literature of religious
      conversion, the authors suggest three principal similarities and the point of
      departure between the two phenomena. 

PMID- 24306756
TI  - Religion and the theory of masochism.
AB  - The various aspects of masochistic personality structures provide a useful model
      for examining familiar elements of ordinary religious life. Overall theories of
      masochism can be divided into six general categories which trace masochism to 1)
      a distortion of love, 2) a need for punishment, 3) a payment for future rewards,
      4) a strategy of the weak or powerless, 5) a flight from selfhood, or 6) an
      effort to be an object for others. In each case, religious analogies can be found
      exhibiting the same dynamics. Thus, certain religious phenomena may provide
      cultural or collective responses to the psychological needs at the root of
      masochism.240. 

PMID- 24306757
TI  - Healing and health care of the whole person.
AB  - What happened to the ancient art of healing when the modern science of medicine
      came into being? Recent alternatives of treating the body to keep it well are
      intrinsically linked to the social and religious development of our society.
      Holistic medicine may involve the rediscovery of many old ways that have been
      lost or forgotten. This article attempts to introduce healing as an aspect of all
      health care and particularly of the holistic model of health care. This model
      certainly includes biomedicine, but its parameters may be very much greater. 

PMID- 24306758
TI  - The hospice: Humane care for the dying.
AB  - The hospice movement arose as a reaction to the dehumanizing atmosphere of acute
      care hospitals, where excessive utilization of life support equipment deprived
      dying patients of a meaningful vision of their destiny. Respecting the spiritual
      quest of the terminally ill for wholeness and dignity, the hospice concept
      prescribes the rendering of compassionate and pastoral care by a benevolent
      community of family, health care staff, friends, and clergy. Approximately 800
      hospice programs are currently evolving in the United States. St. Mary's
      (formerly "Hillhaven") Hospice in Tucson, Arizona, offers the most comprehensive
      program of services, including home care, inpatient care, and artistic media
      through which the dying express their creativity. Numerous demonstration projects
      funded by several government agencies, principally the Health Care Financing
      Administration (HCFA), are expected to result in the legislative actions
      eliminating barriers to reimbursement of the cost of hospice services by
      Medicare, Medicaid, and other third-party payers. Existential analysis reveals
      the value of religion and spiritual support in enabling the dying to banish
      anxiety and muster the hope requisite for fully appreciating the authentic
      meaning of their destiny. 

PMID- 24306759
TI  - Identification of the epitopes of monoclonal antibodies against P74 of
      Helicoverpa armigera nucleopolyhedrovirus.
AB  - P74 is a per os infectivity factor of baculovirus. Here, we report the production
      of three monoclonal antibodies (mAbs), denoted as 20D9, 20F9 and 21E1, raised
      against P74 of Helicoverpa armigera nucleopolyhedrovirus (HearNPV), and the
      identification of their recognition epitopes. The full-length P74, without the
      transmembrane domains at the C-terminus, was first divided into three segments
      (N, M and C, respectively), based on the proposed cleavage model for the protein,
      which were then expressed individually. Western blot analyses revealed specific
      cross-reactions with the N fragment, for both 20D9 and 21E1. Extensive
      truncation, followed by prokaryotic expression, of the P74 N fragment was then
      performed in order to screen for linear epitopes of P74. The recognition regions
      of 20D9 and 21E1 were revealed to be localized at R144-T153 and T199-C219,
      respectively. In addition, immunofluorescence microscopy indicated that 20D9 and
      20F9 could recognize native P74 in HearNPV-infected cells. These findings will
      facilitate further investigations of the proteolytic processing of HearNPV P74,
      and of its involvement in virus-host interactions. 

PMID- 24306760
TI  - Snapshots of a viral RNA polymerase switching gears from transcription initiation
      to elongation.
AB  - During transcription initiation, RNA polymerase binds tightly to the promoter DNA
      defining the start of transcription, transcribes comparatively slowly, and
      frequently releases short transcripts (3-8 nucleotides) in a process called
      abortive cycling. Transitioning to elongation, the second phase of transcription,
      the polymerase dissociates from the promoter while RNA synthesis continues.
      Elongation is characterized by higher rates of transcription and tight binding to
      the RNA transcript. The RNA polymerase from enterophage T7 (T7 RNAP) has been
      used as a model to understand the mechanism of transcription in general, and the
      transition from initiation to elongation specifically. This single-subunit enzyme
      undergoes dramatic conformational changes during this transition to support the
      changing requirements of nucleic acid interactions while continuously maintaining
      polymerase function. Crystal structures, available of multiple stages of the
      initiation complex and of the elongation complex, combined with biochemical and
      biophysical data, offer molecular detail of the transition. Some of the crystal
      structures contain a variant of T7 RNAP where proline 266 is substituted by
      leucine. This variant shows less abortive products and altered timing of
      transition, and is a valuable tool to study these processes. The structural
      transitions from early to late initiation are well understood and are consistent
      with solution data. The timing of events and the structural intermediates in the
      transition from late initiation to elongation are less well understood, but the
      available data allows one to formulate testable models of the transition to guide
      further research. 

PMID- 24306761
TI  - T-DNA genes to study plant development: precocious tuberisation and enhanced
      cytokinins in A. tumefaciens transformed potato.
AB  - Potato Line Mb1501B is a derivative of the cultivar Maris Bard (Solanum
      tuberosum), transformed with T-DNA from A. tumefaciens strain LBA1501. In culture
      it grew as frequently branching stunted shoots with a basal callus, lacking
      roots. These shoots did not form tubers. When grafted, Mb1501B shoots gradually
      became morphologically more normal and aerial tubers formed readily. Cultured
      Mb1501B shoots contained 100-200-fold higher concentrations of the biologically
      active cytokinins zeatin, zeatin riboside and their corresponding side-chain o
      glucosides than untransformed Maris Bard shoots. Cultured Mb1501B shoots
      contained approximately a 3-fold lower concentration of indole acetic acid (IAA).
      In grafted Mb1501B plants a 3-10-fold higher concentration of the active
      cytokinins was found compared with untransformed plants and no difference in IAA
      concentration. 

PMID- 24306762
TI  - Expression of shoot-inducing Ti TL-DNA in differentiated tissues of potato
      (Solanum tuberosum cv Maris Bard).
AB  - In potato line Mb1501B one or possibly two normal size Ti TL-DNA copies per
      tetraploid genome were detected by Southern blot analysis, but no TR-DNA. The TL
      DNA probably contained the entire transposon Tn1831 inserted at the T-DNA auxin
      gene for transcript 2. Northern blot analyses of the steady-state RNA in
      different Mb1501B tissues isolated from (i) shoots cultured in vitro (ii) grafted
      plants and (iii) tubers, showed that that TL-DNA transcripts 3, 4, 6a and 7 were
      expressed most abundantly in the cultured shoots. They formed approximately
      0.0023 to 0.0007% of the total poly(A) RNA. Transcripts 1, 5 and 6b were not
      detected in any of the tissues analysed. This indicated even lower levels of
      expression (below approximately 0.0001% of the total poly(A) RNA or, making
      certain assumptions, an abundance of less than one T-DNA derived RNA molecule per
      cell). As expected, transcript 2 was not detected in any of the Mb1501B tissues.
      The abundance of the transcripts was reduced in grafted plants and tubers
      compared with cultured shoots with the greatest decrease (5*) for transcripts 4,
      6a and 7. Transcript 4, the one most responsible for the changed growth and
      development of Mb 1501 B, formed approximately 0.0003% of the poly(A) RNA from
      both grafted plants and tubers. 

PMID- 24306763
TI  - Structure and expression of DNA transferred to tobacco via transformation of
      protoplasts with Ti-plasmid DNA: co-transfer of T-DNA and non T-DNA sequences.
AB  - The T-DNA structure and organization in tissues obtained via transformation of
      tobacco protoplasts with Ti-plasmid DNA was found to be completely different from
      the T-DNA introduced via Agrobacterium tumefaciens. It is often fragmented.
      Overlapping copies of T-DNA, having various sizes, as well as separated fragments
      of T-DNA were detected. The border sequences of 23 basepairs (bp), flanking the T
      region in the Ti-plasmid as direct repeats are not used as preferred sequences
      for integration. Similar results were obtained with a T-region clone lacking one
      of the TL-borders. This clone, which carried the cytokinin locus and only the
      right border sequence of TL and the left border sequence of TR, still had the
      capacity to transform protoplasts. Also the Vir-region of the Ti-plasmid is not
      required for integration of foreign DNA via DNA transformation. This is
      demonstrated by the results with the T-region clone mentioned and by the
      transforming capacity of a Ti-plasmid carrying a mutated Vir-region.
      Nevertheless, in a number of Ti-plasmid DNA transformants Vir-region fragments
      were found to be stably integrated. Furthermore, it has been established that co
      transformation can occur with plant cells. Besides the detection of Ti-plasmid
      fragments from outside the T-region also DNA sequences originating from two DNA
      sources, which were both independently present in transformation experiments,
      have been found in some DNA transformants, e.g. calf thymus DNA, which was used
      as carrier DNA. No expression of the co-transferred DNA was observed. In total
      three phenotypical classes of DNA transformants were isolated. Although the T-DNA
      was often scrambled, polyA(+) mRNA studies indicated that the different
      phenotypes studied can be explained by the presence of active T-DNA genes with
      known functions. 

PMID- 24306764
TI  - Transformation of plant protoplasts with DNA: cotransformation of non-selected
      calf thymus carrier DNA and meiotic segregation of transforming DNA sequences.
AB  - With the DNA transformation procedure developed in our laboratory (13) several
      transformed tobacco SR1 tissues were obtained which, apart from selected and non
      selected pTi sequences (T(+)), also had acquired non-selected calf thymus carrier
      DNA sequences (C(+)), being integrated in their nuclear genomes. From one such
      tissue (cNT4), with a shooty crown gall phenotype and expressing mannopine
      synthesis activity (Mas(+)), shoots were grafted and mature, flowering plants
      (gNT4) were obtained. After cross pollination with wild type SR1 tobacco pollen
      49% of the seedlings obtained, had the maternal NT4-like crown gall phenotype and
      51% showed wild type (SR1) features. The mannopine locus segregated independently
      from the locus determining the crown gall phenotype. When screened for integrated
      ('transforming') foreign DNA sequences 97% of the NT4-like seedlings turned out
      to be C(+)T(+). Most of the SR1-like seedlings, having a wild type tobacco
      morphology, proved to be transformed as well: roughly a 1:1:1:1 ratio as found
      for C(+)T(+):C(-)T(+): C(+)T:C T SR1-like seedlings. Based on the segregation of
      transforming sequences during meiosis a model is presented showing the
      integration of these sequences in three different host chromosomes. 

PMID- 24306765
TI  - The nucleosome structure of the rRNA genes of some tumorous and nontumorous
      Nicotiana cell lines.
AB  - The nucleosome structure of the nuclear rRNA genes was investigated in a variety
      of tumorous and nontumorous Nicotiana tabacum cell lines, and in a genetic tumor
      produced by crossing Nicotiana langsdorffii with Nicotiana glauca. The rRNA genes
      from two unorganized octopine type crown gall tumors were found in an altered
      nucleosome conformation compared to those of the other cell lines and N. tabacum
      leaves. The altered nucleosome structure of the rRNA genes in the octopine type
      crown gall lines was not due to the tumorous state of the tissue, nor was it
      related directly to the morphology of the tumor. These two lines did have,
      however, a greatly reduced rRNA gene copy number. Several Eco R1 fragments
      homologous to the rRNA gene probe were preferentially lost from one of these
      tumor lines. The alteration of the nucleosome structure of the remaining rRNA
      genes in the octopine type crown gall tumors may result from rapid transcription
      necessitated by their reduced copy number. 

PMID- 24306766
TI  - Activity expressed from cloned Anacystis nidulans large and small subunit
      ribulose bisphosphate carboxylase genes.
AB  - The ribulose bisphosphate carboxylase/oxygenase (EC4.1.1.39) (RubisCO) large and
      small subunit genes from Anacystis nidulans have been cloned as a single fragment
      into M 13mp10 and pEMBL8 and expressed in Escherichia coli. From M 13mp10 a low
      yield of enzyme with high specific activity was obtained. The molecular weight of
      the active enzyme was 260 000 Da and of the inactive enzyme approximately 730 000
      Da. The small and large subunits cloned separately did not express activity. The
      RubisCO gene cloned into pEMBL8 expressed activity up to 22 times that from the M
      13 cloned RubisCO DNA. The RubisCO protein produced by the pEMBL cloned gene had
      a normal MW (550 000). Immunoprecipitation and polyacrylamide gel electrophoresis
      showed the presence of both large and small subunits. 

PMID- 24306767
TI  - Comparison of pedometer and accelerometer derived steps in older individuals with
      Parkinson's disease or osteoporosis under free-living conditions.
AB  - AIM: To compare self-reported pedometer steps with accelerometer steps under free
      living conditions in individuals with Parkinson's disease (PD) or osteoporosis
      (OP). METHODS: Seventy-three individuals with PD and 71 individuals with OP wore
      a pedometer (Yamax LS2000) and an accelerometer (ActiGraph GT1M/GT3X+)
      simultaneously for one week. RESULTS: Fifty-one individuals with PD (72.6 +/- 5.3
      years) and 61 with OP (75.6 +/- 5.3 years) provided simultaneously recorded data
      for 3-7 consecutive days. Pedometer steps were significantly lower than
      accelerometer steps in the PD group (p = .002) but not in the OP group (p =
      .956). Bland-Altman plots demonstrated wide limits of agreement between the
      instruments in both PD (range = 6,911 steps) and OP (range = 6,794 steps).
      CONCLUSION: These results suggest that the ActiGraph GT1M/GT3X+ should be
      preferred over the Yamax LS2000 for the assessment of steps in both research and
      clinical evaluations, particularly in individuals with PD or altered gait.

PMID- 24306768
TI  - Then and now: a systematic review of the systematics of prokaryotes in the last
      80 years.
AB  - In the 80 years that have passed since the first issue of Antonie van Leeuwenhoek
      was published, the field of prokaryote systematics has changed dramatically. The
      4th edition of Bergey's Manual of Determinative Bacteriology (1934) described 132
      genera and 2,703 species. The numbers of genera and species with names with
      standing in the nomenclature in August 2013 were 2,390 and 11,482, respectively,
      including no more than 75 genera and 250 species that were recognized in 1934. In
      the years 2006-2012, on average 624 new species were added annually, most of
      which were described by scientists in Asian countries. We review the past and
      current species concept for the prokaryotes and the current requirements for the
      description of new species, based on a 'polyphasic' approach. We discuss the
      impact of genomics and metagenomics and other new trends toward revitalization of
      prokaryote systematics, and provide some ideas and speculations on possible
      future developments in the field. 

PMID- 24306769
TI  - Streptomyces tunisiensis sp. nov., a novel Streptomyces species with
      antibacterial activity.
AB  - A novel actinomycete strain designated CN-207(T) was isolated from northern
      Tunisian soil. This strain exhibited potent broad spectrum antibacterial activity
      against clinical isolates of methicillin-resistant Staphylococcus species and
      several other Gram-positive and Gram-negative bacteria. Strain CN-207(T)
      developed greyish aerial mycelium and pale grey substrate mycelium on yeast
      extract/malt agar. The isolate produced branching vegetative mycelia with
      sporangiophores bearing sporangia developing at a late stage of growth. The
      sporangia contained smooth, non-motile spores. Chemotaxonomic characteristics of
      strain CN-207(T) were typical of the Streptomyces genus. Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that strain CN-207(T) belonged to the
      genus Streptomyces, and was most closely related to Streptomyces griseoincarnatus
      DSM 40274(T), Streptomyces variabilis DSM 40179(T), Streptomyces labedae DSM
      41446(T) and Streptomyces erythrogriseus DSM 40116(T). Low DNA-DNA relatedness
      values were recorded between strain CN-207(T) and its closest phylogenetic
      neighbours. Strain CN-207(T) was also distinguished from the nearest phylogenetic
      neighbours using a combination of morphological and phenotypic characteristics.
      On the basis of its phenotypic and molecular properties, strain CN-207(T) is
      considered as a novel species of the Streptomyces genus, for which the name
      Streptomyces tunisiensis sp. nov. is proposed. The type strain is CN-207(T) (=JCM
      17589(T) = DSM 42037(T)).

PMID- 24306770
TI  - Triple test cross analysis in F2 populations of four barley crosses.
AB  - The triple test cross analysis of Jinks and Perkins (1970) was used to study
      different components of genetic variation in four barley F2 populations, C 164x
      IB 226, C 164xJyoti, IB 226xP 113 and DL 3xP 113, for final plant height, spike
      length, 100-kernel weight, grain yield per plant and harvest index. The overall
      epistasis (i type) was, in general, a minor component but the j & 1 type
      epistasis was an important element for all five characters in cross 3 (IB 226xP
      113). Both the additive (D) and dominance (H) components were highly significant
      for all the five characters in all four crosses. The dominance was directional in
      all cases except for 100-grain weight in crosses 1 (C 164xIB 226), 2 (C
      164xJyoti) and 4(DL 3xP 113). 

PMID- 24306771
TI  - 'Nucleolar dominance' as observed in barley translocation lines with specifically
      reconstructed SAT chromosomes.
AB  - Diploid homo- and heterokaryotypes of barley translocation lines with only one
      satellite chromosome pair containing two nucleolus organizer regions (NORs) in
      opposite arms were found to show repressed nucleolus formation by the transposed
      NOR as evident from the formation of only micronucleoli. The same was true for
      auto-tetraploid homokaryotypes and for translocation lines with all NORs tandemly
      arranged into the same chromosome arm. When NORs were transposed to chromosomes
      without NOR in the standard karyotype, the normal pattern of nucleolus formation
      remained unaffected. The modified mode of nucleolus formation after the
      combination of all NORs in one chromosome pair is interpreted to be due to
      intrachromosomal nucleolar dominance analogous to interchromosomal nucleolar
      dominance observed in certain interspecific hybrids. 

PMID- 24306772
TI  - Organophosphate induced chlorophyll mutations in Hordeum vulgare.
AB  - Ten Organophosphorus (OP) insecticides are tested for their genetic toxicology in
      the Hordeum vulgare system. Of these, 8 OPs induced chlorophyll mutations of
      which 6 are new discoveries. 

PMID- 24306773
TI  - Biochemical selection of immature, haploid embryos of Zea mays L.
AB  - A method was devised for the biochemical selection of immature, haploid Zea mays
      embryos using Adh1 (-) and either the Stock 6 or indeterminate gametophyte (ig in
      W23) high haploid-inducing systems. Haploid (Adh1 (-)) embryos survived exposure
      to levels of allyl alcohol which killed diploid (Adh1 (+)/Adh1 (-)) embryos. Of
      the total surviving embryos which were examined cytologically 15% (using ig) and
      22% (using Stock 6) were haploid. In two experiments with Stock 6, 100% of the
      surviving embryos were haploid. To obtain maximum effectiveness of Stock 6 and
      ig, Adh1 (-) was transferred to stock 6 and W23 backgrounds. Immature, haploid
      embryos are being used to develop haploid, morphogenic tissue cultures of Zea
      mays. 

PMID- 24306774
TI  - Some consequences of selection for fast and slow recovery from the larval alarm
      reaction in Aedes aegypti.
AB  - Replicated divergent selection based upon the time taken to recover from the
      larval alarm reaction in the mosquito Aedes aegypti resulted in lines which
      recovered faster and slower than the control lines. Estimates of the realized
      heritability were consistent, ranging from 0.21 to 0.24 in the fast replicates
      and 0.19 to 0.20 in the slow replicates. After 11 generations of selection an
      apparent change in the fitness was examined using an application of the path
      analysis. The relevance of the findings to natural selection is also discussed. 

PMID- 24306775
TI  - Cytoplasmic male sterility in barley : Part 4: effect of msm1 cytoplasm and
      partial fertility on kernel protein and lysine.
AB  - The effect of the msm1 cytoplasm of barley (Hordeum vulgare L.) on kernel protein
      and lysine was studied using the near-isogenic, unrestored derivatives of seven
      barley varieties. With normal lysine varieties, 'Adorra', 'Bomi', 'CI 4362', and
      'Hankkija's Eero', the msm1 cytoplasm produced an average of one percentage point
      more protein than did the normal cytoplasm of the same varieties. There was no
      difference between the two cytoplasms with respect to their effect on the lysine
      content. With high lysine varieties, 'Bomi Riso mutant 13', 'Bomi Riso mutant
      1508', and 'CI 3947', msm1 produced almost one percentage point more protein but
      protein with a somewhat decreased lysine content.Induced partial spike fertility
      in normal 'Adorra' was found to be associated with lysine in meal (r=-0.999),
      with protein in meal (r=-0.984), and with lysine in protein (r=0.941). Removal of
      the spikes on the secondary tillers affected both the protein and its lysine
      content. It is suggested that good spike fertility is an important pre-requisite
      when selecting high lysine and/or high protein segregants or mutants. 

PMID- 24306776
TI  - Isolation and characterization of anthocyanin variants originating from the
      unstable system an2-1 in Petunia hybrida (Hort.).
AB  - Forty stable an2-n alleles, derived from the unstable system an2-1, have been
      tested for anthocyanin synthesis. All of them proved to be different from both
      the An2 and an2 natural alleles. Only two were distinct from the others which
      according to Duncan's multiple range test formed a group of overlapping
      populations. Amongst the variants isolated there was a large majority of light
      coloured types. Regulation-like effects of the an2-n alleles on the subsequent
      genes of the anthocyanin pathway have been observed. A hypothesis concerning the
      nature of the genetic events occurring at the An2 locus is discussed. 

PMID- 24306777
TI  - Fisher's reticulate mating system for immigration into an improved stock.
AB  - A reticulate mating system is described which was designed by the late R.A.
      Fisher to permit the introduction of new genetic variability into an improved
      stock by immigration. Analysis of part of a long-term experiment to alter the
      degree of dominance of the mutant Sd in mice using the system demonstrates a
      rapid response. Its applicability to stocks of animals of economic value is
      considered. 

PMID- 24306778
TI  - Structural investigation of protonated azidothymidine and protonated dimer.
AB  - Infrared multiple photon dissociation (IRMPD) spectroscopy experiments and
      quantum chemical calculations have been used to explore the possible structures
      of protonated azidothymidine and the corresponding protonated dimer. Many
      interesting differences between the protonated and neutral forms of
      azidothymidine were found, particularly associated with keto-enol
      tautomerization. Comparison of computational vibrational and the experimental
      IMRPD spectra show good agreement and give confidence that the dominant
      protonated species has been identified. The protonated dimer of azidothymidine
      exhibits three intramolecular hydrogen bonds. The IRMPD spectrum of the
      protonated dimer is consistent with the spectrum of the most stable computational
      structure. This work brings to light interesting keto-enol tautomerization and
      exocyclic hydrogen bonding involving azidothymidine and its protonated dimer. The
      fact that one dominant protonated species is observed in the gas phase, despite
      both the keto and enol structures being similar in energy, is proposed to be the
      direct result of the electrospray ionization process in which the dominant
      protonated dimer structure dissociates in the most energetically favorable way. 

PMID- 24306779
TI  - "Best match" model and effect of Na+/H+ exchange on anion attachment to peptides
      and stability of formed adducts in negative ion electrospray mass spectrometry.
AB  - The "Best Match" model has been extended to account for the role that Na(+)/H(+)
      exchange plays on anion attachment in negative ion electrospray. Without any
      Na(+)/H(+) exchange on (Glu) fibrinopeptide B, the higher basicity anions F(-)
      and CH3COO(-) can hardly form observable adducts; however, after multiple
      Na(+)/H(+) exchanges, adduct formation is enabled. Moreover, dissociation
      pathways of CF3COO(-) adducts with singly deprotonated peptides that have
      undergone 0 to 3 Na(+)/H(+) exchanges exhibit a shift in CID product ions from
      losing predominately CF3COOH (case of 0 Na(+)/H(+) exchanges) to losing
      predominately CF3COO(-) (case of 3 Na(+)/H(+) exchanges). These phenomena can be
      rationalized by considering that Na(+) cations exchange at, and serve to "block",
      the most acidic sites, thereby forcing implicated anions to attach to lower
      acidity protons. In addition to forming ion pairs with carboxylate groups, Na(+)
      also participates in formation of tri-atomic ions of the form ANaA(-) during
      adduct dissociation. The fact that low gas-phase basicity (GB) anions
      preferentially form ANaA(-) species, even though high GB anions form more stable
      tri-atomic species, indicates that the monatomic ions were not in close contact
      in the initial adduct. The propensity for formation of stable anionic adducts is
      dependent on the degree of matching between anion GBs and GBapp of deprotonated
      sites on the peptide. The GBapp is raised dramatically as the charge state of the
      peptide increases via a through-space effect. The presence of Na(+) on
      carboxylate sites substantially decreases the GBapp by neutralizing these sites,
      while slightly increasing the intrinsic GBs by an inductive effect. 

PMID- 24306780
TI  - Sulfolobus solfataricus thiol redox puzzle: characterization of an atypical
      protein disulfide oxidoreductase.
AB  - Protein disulfide oxidoreductases (PDOs) are proteins involved in disulfide bond
      formation playing a crucial role in adaptation to extreme environment. This paper
      reports the functional and structural characterization of Sso1120, a PDO from the
      hyperthermophilic archaeon Sulfolobus solfataricus. The protein was expressed in
      Escherichia coli and purified to homogeneity. The functional characterization
      showed that the enzyme has reductase activity, as tested by insulin assay, but
      differently from the other PDOs, it does not present isomerase activity. In
      addition it is able to form a redox couple with the thioredoxin reductase that
      could be used in undiscovered pathways. The protein revealed a melting point of
      around 90  degrees C in CD spectroscopy-monitored thermal denaturation and high
      denaturant resistance. The X-ray crystallographic structure was solved at 1.80 A
      resolution, showing differences with respect to other PDOs and an unexpected
      similarity with the N-terminal domain of the alkyl hydroperoxide reductase F
      component from Salmonella typhimurium. On the basis of the reported data and of
      bioinformatics and phylogenetic analyses, a possible involvement of this atypical
      PDO in a new antioxidant system of S. solfataricus has been proposed. 

PMID- 24306782
TI  - Bioorganic chemistry of communication systems.

PMID- 24306781
TI  - Bacterial chitin utilization at halophilic conditions.
AB  - Chitin is a dominant structural polymer produced in large amounts by brine shrimp
      Artemia in hypersaline lakes. Microbiological analysis of chitin utilization as a
      growth substrate in hypersaline chloride-sulfate lakes in the south Kulunda
      Steppe (Altai, Russia) revealed two groups of bacteria able to grow on chitin at
      moderate salinity. Under aerobic conditions, an enrichment culture was obtained
      at 2 M NaCl. Further purification resulted in the isolation of strains HCh1 and
      strain HCh2, identified as representatives of the genera Saccharospirillum and
      Arhodomonas (both in the Gammaproteobacteria). The chitin-utilizing potential has
      not been previously recognized in these genera. The Saccharospirillum sp. strain
      HCh1 grew on chitin within the salinity range from 0.5 to 3.25 M NaCl (optimum at
      1 M), while Arhodomonas sp. strain HCh2 grew up to 2.5 M NaCl but had a higher
      salt optimum at 1.5 M. Anaerobic enrichments grew with chitin at 2 and 4 M NaCl,
      but growth in the latter was extremely slow and the culture eventually lost
      viability. The enrichment at 2 M NaCl resulted in the isolation of strain HCh
      An1, identified as a distant new species of the genus Orenia in the clostridial
      order Halanaerobiales. It was able to grow on chitin within a salinity range from
      1.0 to 2.5 M NaCl (optimum at 1.5 M). The strain is proposed as a new species of
      the genus Orenia-O. chitinitropha. 

PMID- 24306783
TI  - Binding and hydrolysis of radiolabeled pheromone and several analogs by male
      specific antennal proteins of the mothAntheraea polyphemus.
AB  - Sensory hair proteins from antennae of males of the wild silk moth,Antheraea
      polyphemus (Lepidoptera, Saturniidae) were incubated with radiolabeled 6E,11Z
      hexadecadienyl acetate in the presence of unlabeled pheromone analogs as
      competitive inhibitors. The two extracellular proteins of importance, a highly
      active sensillar esterase and an abundant 15,000 mol wt binding protein, interact
      to degrade labeled pheromone less efficiently in the presence of certain
      unsaturated acetate analogs of the natural pheromone.Enzymatic hydrolysis of the
      acetate (or diazoacetate) was also examined for three pheromone analogs: [11,12
      (3)H2]-6E,11Z-hexadecadienyl diazoacetate, [11,12-(3)H2]-hexadecyl acetate, and
      [9,10-(3)H2]-9Z-tetradecenyl acetate. The former two are poor substrates at
      concentrations over four orders of magnitude. The 9Z-14:Ac, however, is the best
      alternative substrate for this in vitro pheromone metabolism system. Unlabeled 9Z
      14: Ac is also the best competitive inhibitor of the hydrolysis of labeled 6E,
      11Z-16: Ac. Whereas the tritiated natural pheromone shows a flat response (ca.
      40% conversion) to increasing concentrations from 3 * 10(-9) to 3 * 10(-6) M,
      tritiated 9Z-14: Ac is degraded more rapidly at higher concentrations. 

PMID- 24306784
TI  - Pheromone biosynthesis and role of functional groups in pheromone specificity.
AB  - The sex attractants for many Lepidoptera are long-chain, monounsaturated acetate
      esters, alcohols, and aldehydes. In vivo metabolic studies and enzyme analysis in
      vitro have provided evidence that the aldehyde pheromone of the eastern spruce
      budworm is synthesized de novo via an acetate ester precursor. Interconversion of
      the functional groups (ester, alcohol, aldehyde) can explain differences in the
      pheromone blends used by closely related species. 

PMID- 24306785
TI  - Terminal steps in pheromone biosynthesis byHeliothis virescens andH. zea.
AB  - In vivo application to the sex pheromone gland ofHeliothis Virescens andH. Zea of
      large quantities of alcohols normally present in small amounts resulted in the
      preferential conversion of the alcohols to the corresponding pheromonal
      aldehydes. Amounts of the minor component aldehydes were increased up to 15-fold
      by selectively applying large quantities of the alcohol precursors. Using this
      technique, we have inducedH. virescens to convert "bombykol," the sex pheromone
      of the silkworm, to the corresponding aldehyde, "bombykal," and have induced
      femaleH. zea to produce the same sex pheromone components used byH. virescens by
      applying tetradecanol and (Z)-9-tetradecenol to the surface of the gland.
      Further, treatedH. zea females were attractive toH. virescens males and caused
      males to attempt interspecific copulation repeatedly. We have also found that the
      enyzme involved in this conversion is dependent on the presence of molecular
      oxygen, indicating that a nonspecific alcohol oxidase is responsible for the
      terminal biosynthetic step in pheromone production by bothH. virescens andH. zea.

PMID- 24306786
TI  - Spruce budworm (Choristoneura fumiferana) pheromone chemistry and behavioral
      responses to pheromone components and analogs.
AB  - This paper reviews the sex pheromone chemistry and pheromone-mediated behavior of
      the spruce budworm and related coniferophagous (Choristoneura) budworms. InC.
      fumiferana, temporal changes in pheromone-gland monounsaturated fatty acids
      (pheromone precursors) enable the prediction of the primary sex pheromone
      components. This technique may also be applicable for predicting additional
      pheromone components. Tetradecanal (14? Ald), previously shown to enhance close
      range precopulatory behavior, lowers the threshold of response by males for
      upwind flight to a pheromone-component source. Spruce budworm males maintain
      upwind flight to 95?5 (E/Z)-1,12-pentadecadiene (diolefin analog) after
      initiating upwind flight to a primary-component pheromone source (95?5E/Z11
      14?Ald). This is the first demonstration of apparently normal male flight
      responses to a pheromone analog. 

PMID- 24306787
TI  - Pheromones of two arctiid moths (Creatonotos transiens andC. gangis) : Chiral
      components from both sexes and achiral female components.
AB  - The two major components of the female sex pheromones of twoCreatonotos species
      have been identified as an achiral C21 triene, (Z,Z,Z)-3,6,9-heneicosatriene, and
      a chiral epoxide, (Z,Z)-2(2,5-octadienyl)-3-undecyloxirane. The ratios of these
      components in the two species fall into nonoverlapping ranges. Two additional
      achiral minor components, (Z,Z)-6,9-heneicosadiene and (Z,Z,Z)-3,6,9
      tricosatriene, were also identified in the female sex gland extracts. The male
      pheromone of both species consists of hydroxydanaidal, a chiral
      dihydropyrrolizine derived from pyrrolizidine alkaloids in the larval
      diet.Creatonotos transiens was found to convert dietary heliotrine into (R)-(-)
      hydroxydanaidal, with inversion at the single asymmetric carbon atom. The
      possible biological and biosynthetic significance of the chiral pheromone
      components are discussed, and they are compared with known examples of chiral
      lepidopteran pheromones. 

PMID- 24306788
TI  - Metabolic transformation of tritium-labeled pheromone by tissues ofHeliothis
      virescens moths.
AB  - Unsaturated aliphatic pheromones ofH. VIRESCENS were prepared at high specific
      activity ((3)H, 58 Ci/mmol) and were employed to study tissue specificity of
      acetate esterase, alcohol oxidase, and aldehyde dehydrogenase in male and
      femaleHeliothis virescens. Thus, [9,10-(3)H2]Z9-14:Ac was synthesized by partial
      tritiation of the corresponding alkyne and was converted to the labeledZ9-14?OH
      andZ9-14?Al for metabolic studies. Soluble and membrane-associated enzyme
      activities were determined by radio-TLC assays. Esterase activity is highest in
      legs of both sexes, but also occurs in antennal and glandular tissues. Oxidase
      activity requires O2 and is highest in female pheromone gland tissues, but it is
      also high in the male hairpencils. Aldehyde dehydrogenase activity was uniformly
      high in all tissues, but highest in antennal tissues of both males and females. 

PMID- 24306789
TI  - Sex pheromone biosynthesis in the red-banded leafroller moth, studied by mass
      labeling with stable isotopes and analysis with mass spectrometry.
AB  - A technique for mass-labeling was developed to study sex pheromone biosynthesis
      in the red-banded leafroller moth,Argyrotaenia velutinana. With this technique,
      the pheromone components and all fatty acyl groups in the pheromone gland were
      analyzed for incorporation of label in the same analytic ran with gas
      chromatography-mass spectrometry, using chemical ionization and selected ion
      monitoring (GC-SIM-CI-MS). Sex pheromone glands were incubated with fatty acids
      or triacylglycerols labeled with at least three deuterium atoms or carbon-13
      atoms. The results of these incubations support an interpretation in which
      hexadecanoate is chain shortened to tetradecanoate, which is desaturated to
      produce (E)- and (Z)-11-tetradecenoate precursors for the sex pheromone
      components (E)- and (Z)-11-tetradecen-1-yl acetate. Labeled (E)- and (Z)-11
      tetradecenoyl groups in synthetic triacylglycerols were not incorporated into the
      sex pheromone components, perhaps indicating that this lipid class is not a donor
      of the immediate fatty acyl precursors in sex pheromone biosynthesis. 

PMID- 24306790
TI  - Insect olfactory receptor responses to components of pheromone blends.
AB  - Multicomponent pheromone systems are common in many insect species. As our
      knowledge about the number of different chemical compounds actually involved in a
      particular communication system increases, so too does the need for an efficient
      neural mechanism for the encoding of behaviorially relevant odor compounds. Here
      we consider the electrical activity of olfactory receptor neurons in a subset of
      the individual pheromone-sensitive sensilla on the antennae of male cabbage
      looper moths (Trichoplupia ni). Responses to single- and multiple-component
      stimuli, drawn from seven behaviorally active compounds, were obtained at several
      different intensities. Some blends elicited electrical responses which were not
      readily predicted from a knowledge of the receptor neuron's response to
      individual components. 

PMID- 24306791
TI  - Scale esterase : A pheromone-degrading enzyme from scales of silk mothAntheraea
      polyphemus.
AB  - Body scales of the silk mothAntheraea polyphemus contain an esterase which can
      degrade the female sex pheromone of this species. This esterase, which appears to
      be stabilized to the scale cuticle, is present in both sexes, but is species
      specific. The enzyme may play a significant role in the behaviors associated with
      sex-pheromone attraction, helping to filter out stimulus noise by degrading
      adsorbed pheromone, thus preventing adsoptive body surfaces from becoming
      uncontrolled pheromone sources. 

PMID- 24306792
TI  - Metabolism of pheromone components and analogs by cuticular enzymes
      ofChoristoneura fumiferana.
AB  - In vivo incubation ofChoristoneura fumiferana with (E)-11-tetradecenal, the major
      pheromone component, resulted in adsorption followed by transformation to (E)-11
      tetradecenoic acid, the only observed metabolite. Antennae, legs, and wings from
      both sexes were investigated for enzyme activity. Specificity studies with the
      aldehyde dehydrogenase system showed that the enzyme prefers aldehydes of 14
      carbon chain length or shorter. 

PMID- 24306793
TI  - Reproductive endocrine influences upon olfactory perception : A current
      perspective.
AB  - An overview of relationships between psychophysical measures of olfactory
      function and reproductive neuroendocrine processes is presented. Human studies
      are emphasized, and the influences of gender, menstrual cycle phase, pregnancy,
      and injected gonadal hormones upon olfactory perception are discussed in detail. 

PMID- 24306794
TI  - Analysis of chemical signals in a primate species (Saguinus fuscicollis): Use of
      behavioral, chemical, and pattern recognition methods.
AB  - Scent marking with specialized skin glands is a common behavior in the
      tamarin,Saguinus fuscicollis. The scent marks identify species, subspecies,
      gender, and individual, and they also contain information on the social position
      and hormonal condition of an animal. The marks are chemically complex, containing
      a large number of compounds. Analysis by means of gas chromatography-mass
      spectrometry has identified 16 major components (squalene and 15 esters of
      butyric acid). These compounds are present in the marks of males and females of
      two subspecies,Saguinus f. fuscicollis andSaguinus f. illigeri. Application of
      computerized pattern recognition techniques has shown that concentration patterns
      of some of the butyrates are diagnostic of the two subspecies while concentration
      patterns of other butyrates are diagnostic of males and females regardless of
      subspecies. Behavioral studies have shown that the concentration patterns of
      butyrates and squalene alone do not encode information on subspecies and gender.
      It is, however, likely that this information is partially encoded by these
      specific butyrate-squalene concentration patterns but that yet unidentified
      compounds in the scent marks serve as necessary synergists. 

PMID- 24306795
TI  - Enzymatic adaptations of herbivorous insects and mites to phytochemicals.
AB  - A variety of oxidases, reductases, esterases, epoxide hydrolases, and group
      transferases in herbivorous insects and mites detoxify and facilitate the
      excretion of toxic phytochemicals (allelochemicals). Current theory indicates
      that the cytochrome P-450-dependent mixed-function oxidases (MFOs) are by far the
      most important enzymes because they have many attributes that are essential for
      an effective detoxification system. Data presented here on the midgut microsomal
      MFO activity of larvae of the gypsy moth,Lymantria dispar, are discussed in the
      light of previous work and support the theory. In the gypsy moth, the MFO levels
      exhibit a parallel trend with changes in specific feeding rates, and changes in
      the specific activity of the enzyme appear to be regulated ontogenetically and by
      inductive effect of chemicals in the diet. The specific activity of the MFOs
      rises more sharply on leaves of a highly preferred type-1 plant, the pin oak,
      than on an artificial wheat germ diet; the increase from mid-second instar to mid
      fifth is 4.5- and 1.8-fold, respectively. The relationship of food consumption
      rate to increase in body mass (W) was slightly in excess of a 1?1 ratio for both
      pin oak and the artificial diet, indicating that the feeding rate surpasses the
      increase in W (a rare phenomenon in insects). Moreover, the surface-to-volume
      ratios are fairly constant for combined data of gut lumen and epithelium in
      second to fifth instars, because the volume occupied by the epithelial cells is
      much larger than in older ones. Thus, it is concluded that greater specific
      activity of the MFO is necessary with larval advancement to higher instars in
      order that they may process dietary allelochemicals with an efficiency comparable
      to younger larvae. Additional data suggest that MFO level increases reflect
      further adaptation to: (1) normal, seasonal changes in plants' allelochemical
      composition and concentration; (2) increase in allelochemical concentration in
      response to leaf damage; and (3) the risk faced by dispersing larvae of
      encountering a greater amount and variety of allelochemicals on suboptimal/ less
      suitable plants. Evidence also has emerged recently for MFO-catalyzed
      metabolism/deactivation of numerous plant allelochemicals, including compounds
      that induce the enzyme. MFOs are further adapted for participation in the
      biogenesis of substances physiologically important to insects. Moreover, the
      catalytic center of the MFO system, cytochrome P-450, occurs in multiple forms;
      the significance of this important feature is discussed. 

PMID- 24306796
TI  - The haustorium and the chemistry of host recognition in parasitic angiosperms.
AB  - Two parasitic angiosperms,Agalinis purpurea (Scrophulariaceae) andStriga asiatica
      (Scrophulariaceae), are compared as to the chemical recognition events involved
      in host selection.Agalinis is a hemiparasite which can mature to seed-set without
      a host, whereasStriga is a holoparasite and survives for only a very limited time
      without a host. Both parasites, however, attach to a host through a specialized
      organ known as the haustorium and regulate the development of this organ through
      the recognition of chemical factors from host plants. We now describe the
      discovery of 2,6-dimethoxy-p-benzoquinone (2,6-DMBQ) as an haustoria-inducing
      principle fromSorghum root extracts. Our investigation of this compound has led
      us to suggest that one level of host recognition in these parasitic plants is
      mediated through their enzymatic digestion of the host root surface. Degradation
      of surface components liberates quinonoid compounds, such as 2,6-DMBQ, which in
      turn trigger haustorial development. 

PMID- 24306797
TI  - Chloroplast development and the synthesis of chlorophyll a and b and chlorophyll
      protein complexes I and II in the dark in Tradescantia albiflora (Kunth).
AB  - Continued synthesis of chlorophyll a and chlorophyll b occurs in Tradescantia
      albiflora Kunth on transfer to darkness. This synthesis continues for several
      days and may result in a doubling of chlorophyll content per leaf. It is
      accompanied by continued cell division and development of normal chloroplast
      ultrastructure, including stacked thylakoids. 

PMID- 24306798
TI  - A simple system for determining the phloem mobility of compounds using excised
      pods of lupin (Lupinus albus L.).
AB  - Lupin pods were isolated from the plant and the pedicels placed in solutions of
      either radiolabeled sucrose, glucose, abscisic acid, or gibberellin A9 (GA9).
      Phloem exudate was collected from the cut stylar ends of the pods and both
      quantitative and qualitative data were obtained on the activity in the sap. Fed
      sucrose, abscisic acid, and GA9 were found in phloem exudate, but labeled glucose
      was immobile as the monosaccharide and activity in exudate appeared in sucrose. 

PMID- 24306799
TI  - Modulation of L-phenylalanine ammonia-lyase by pathway intermediates in cell
      suspension cultures of dwarf French bean (Phaseolus vulgaris L.).
AB  - The increase in extractable phenylalanine ammonia-lyase (PAL;EC 4.3.1.5.)
      activity induced in French bean cell suspension cultures in response to treatment
      with autoclaved ribonuclease A was inhibited by addition of the phenylpropanoid
      pathway intermediates cinnamic acid, 4-coumaric acid or ferulic acid. The
      effectiveness of inhibition was in the order cinnamic acid>4-coumaric
      acid>ferulic acid. Cinnamic acid also inhibited the PAL activity increase induced
      by dilution of the suspensions into an excess of fresh culture medium. Addition
      of low concentrations (<10(-5)M) of the pathway intermediates to cultures at the
      time of application of ribonuclease gave variable responses ranging from
      inhibition to 30-40% stimulation of the PAL activity measured at 8 h. Following
      addition of pathway intermediates to cultures 4-5 h after ribonuclease treatment,
      rapid increases followed by equally rapid declines in PAL activity were observed.
      The cinnamic acid-stimulated increase in enzyme activity was unaffected by
      treatment with cycloheximide at a concentration which gave complete inhibition of
      the ribonuclease-induced response. However, cycloheximide completely abolished
      the subsequent decline in enzyme activity. Treatment of induced cultures with
      alpha-aminooxy-beta-phenylpropionic acid (AOPPA) resulted in increased but
      delayed rates of enzyme appearance when compared to controls not treated with the
      phenylalanine analogue. The results are discussed in relation to current views on
      the regulation of enzyme levels in higher plants. 

PMID- 24306800
TI  - Efficient translation of long-lived messengers in extracts from dry pea primary
      axes : Evidence for the presence of lectin mRNA.
AB  - Extracts prepared from dry pea (Pisum sativum, L; cv oberon) primary axes
      translate efficiently their endogenous messengers in an in vitro protein
      synthesizing system. The native long-lived messengers are biologically fully
      active and direct the synthesis of a whole range of polypeptides with MW ranging
      up to 130,000. About 0.5% of the total in vitro synthesized polypeptides are
      recovered in the immunoprecipitate obtained with pea lectin antiserum. Since
      about one-fourth of the radioactivity in the immunoprecipitate comigrates with
      authentic pea lectin it is concluded that about 0.1% of the long-lived messengers
      code for the lectin. 

PMID- 24306801
TI  - Rapid separation of the plastid, mitochondrial, and cytoplasmic fractions from
      intact leaf protoplasts of Avena : Determination of in vivo ATP pool sizes during
      greening.
AB  - Purified intact protoplasts were isolated from etiolated and greening leaves of
      Avena sativa. They were ruptured by forcing them through a 20-MUm aperture nylon
      net and immediately thereafter fractionated into a pure pellet of plastids (well
      above 70% of total plastids), a layer of mitochondria only slightly contaminated
      by other cellular constituents (about 50% of total mitochondria), and a
      cytoplasmic supernatant. This was achieved within 60 s by an integrated method of
      homogenation of protoplasts and centrifugal filtration of the homogenate on a
      gradient of silicone oils, contained together with the nylon net in 450 MUl
      microtubes, and verified by comparing the levels of activity of specific markers
      within the three fractions obtained. With appropriate modifications to
      immediately quench metabolic reactions within the fractions, this method allows
      the determination of metabolite levels within plastids, mitochondria, and the
      cytoplasmic compartment of intact protoplasts. The applicability of this
      technique is demonstrated by the determination of ATP in the plastids,
      mitochondria, and the cytoplasm of protoplasts obtained from etiolated and
      greening primary leaves of Avena. The levels of ATP, corrected for contamination
      of the fractions by each other, exhibit a pronounced transient increase during
      greening, especially within the cytoplasm. 

PMID- 24306802
TI  - Effect of chemical inhibitors of photorespiration on nitrogenase activity in
      nodulated alfalfa plants.
AB  - Nitrogen fixation (measured as acetylene reduction) by whole nodulated alfalfa
      plants was stimulated when the plants were treated with isonicotinic acid
      hydracide (INH) and glyoxylate, both inhibitors of the glycolate pathway of
      carbohydrate metabolism, at concentrations of 300 and 100 mM, respectively.
      Reducing energetic loses caused by photorespiration results in an increase in the
      symbiotic nitrogen fixation. 

PMID- 24306803
TI  - Growth, cell volume, and fine structure of Porphyra umbilicalis in relation to
      osmotic tolerance.
AB  - Porphyra umbilicalis, a marine red alga occurring in the intertidal zone of the
      cold North Sea, tolerates a wide range of osmotic conditions from 0.2 x to 6 x
      artificial seawater medium ASP12. In cells osmotically adapted for two weeks,
      photosynthesis and respiration are progressively inhibited in media more
      concentrated than 2 x. In both hypo- and hyperosmotic stress ranges, the most
      striking fine structural change is the development of vacuoles. In comparison to
      1 x medium, where vacuoles are virtually lacking, the vacuolar part of the
      protoplasm increases 6-fold in 0.2 x and 10-fold in 3.5 x medium, respectively.
      However, at extreme hyperosmotic stress (6 x medium) the vacuolar part is
      extremely small. The largest cell volumes are found in 0.2 x and 3.5 x media, the
      smallest one in 6 x medium. In the osmotically regulated range (0.2-3.5 x
      medium), the regulated parameter is the volume of the protoplasm without the
      vacuolar system. It is suggested that at hyperosmotic stress the vacuoles may
      serve as osmotically active compartment, probably by accumulation of inorganic
      ions. The intracellular content of Floridean starch granules decreases with
      increasing osmotic pressure, possibly indicating the significance of soluble
      organic constituents as osmotically active solutes. 

PMID- 24306804
TI  - A study of abscisic acid uptake by apical and proximal root segments of Phaseolus
      coccineus L.
AB  - 1. We investigated the pH and concentration dependence of abscisic acid uptake by
      short segments taken from different zones along the length of primary roots of
      Phaseolus coccineus L. (Runner bean). Tissue from all regions studied, up to and
      including the zone of lateral root initiation showed a non-saturable uptake
      component identifiable with passive diffusion of the undissociated species of
      abscisic acid. The net uptake increased through the elongation zone towards the
      apex, perhaps principally due to the increasing relation volume of cytoplasm (pH
      value 7-8; cf pH 4-6 for vacuole) acting as an anion trap. A saturable uptake
      component, Km=2.6+/-0.8 MUmol dm(-3), is restricted to the apical 4-6 mm of the
      root (including lateral roots), is not of metabolic origin, and is likely to be a
      carrier. 2. No polarity of transport could be detected using donor blocks
      containing [2-(14)C]abscisic acid applied to 15 mm or 40 mm segments whose apical
      10 mm had been removed; if the elongation zone were present in the test segments,
      a distribution of radioactivity that might be expected from acropetal polarity
      was obtained, but which may simply be accounted for by the greater uptake
      capacity of the elongating, relatively unvacuolated cells in the extending region
      of the root. 

PMID- 24306805
TI  - Hormones are no causal links in phytochrome-mediated adventitious root formation
      in mustard seedlings (Sinapis alba L.).
AB  - The question of whether or not hormones are causal links in the realization of
      phytochrome control during photomorphogenesis was investigated using the
      phytochrome-dependent formation of adventitious roots in hypocotyl cuttings
      excised from mustard seedlings as a test system. Histological examination of
      regenerating "rest" seedlings revealed that phytochrome (operationally,
      continuous far-red light) mediates the de novo formation of root primordia in the
      pericycle region of the hypocotyl near the cutting surface withing 12-24 h after
      excision.Auxin (IAA), gibberellin (GA3), Cytokinin (kinetin), abscisic acid
      (ABA), and ethylene had no promotive effect on primordium formation in dark-grown
      or far-red irradiated rest seedlings. Depending on concentration, the application
      of these hormones was either ineffective or inhibitory in the rooting response.
      It is concluded that phytochrome does not operate through changes of hormone
      (auxin, gibberellin, cytokinin, ABA, ethylene) levels.While externally applied
      ethylene had no specific effect on primordium formation, the number of primordia
      produced in darkness could be increased to the far-red light level by removing
      the endogenously formed ethylene. Since the stimulatory effect of light could not
      be related to a lower ethylene level, it is concluded that ethylene interferes
      with primordium formation by modulating the susceptibility of this process to
      phytochrome control. This ethylene effect takes place in a concentration range
      below the range that can be manipulated by external application of the hormone. 

PMID- 24306806
TI  - Isolation and biliprotein characterization of phycobilisomes from the
      thermophilic cyanobacterium Mastigocladus laminosus Cohn.
AB  - A method for the effective isolation of functionally intact phycobilisomes from
      the thermophilic cyanobacterium M. laminosus is presented, using an
      unconventional high buffer molarity for stabilizing the aggregates and
      introducing a DNAse treatment of the disrupted cells to obtain sharp banding of
      the phycobilisomes in the linear sucrose density gradients.The structural
      integrity of the isolated phycobilisomes is demonstrated by a fluorescence
      emission maximum at 673 nm of aggregated allophycocyanin and by electron
      microscopy.Besides C-phycocyanin and allophycocyanin, phycoerythrocyanin is a
      constituent pigment of the phycobilisomes. These pigments indicated in the
      absorption spectrum of phycobilisomes with a maximum at 610 nm and two shoulders
      at 650 and 580 nm, respectively, were characterized by spectral data and
      isoelectric points. 

PMID- 24306807
TI  - Abscisic acid and related compounds in phloem exudate of Yucca flaccida haw. and
      coconut (Cocos nucifera L.).
AB  - Phloem sap collected from Yucca and coconut inflorescence stalks was shown to
      contain abscisic acid (ABA) and trace amounts of 2-trans ABA. In coconut sap, two
      compounds probably derived from ABA with mass spectra consistent with their being
      dihydrophaseic acid and either hydroxyphaseic acid or oxo-dihydrophaseic acid
      were also found to be present. 

PMID- 24306811
TI  - Lives of the Buddha: Vessantara the charitable prince: Thai school.

PMID- 24306808
TI  - When and how do I use neoadjuvant chemotherapy for breast cancer?
AB  - OPINION STATEMENT: Systemic neoadjuvant chemotherapy is utilized along with
      surgery and radiotherapy for the management of patients with locally advanced
      breast cancer. The backbone of current chemotherapy regimens include
      anthracyclines and taxanes given either sequentially or concurrently for up to 8
      cycles. Neoadjuvant treatment benefits include in vivo assessment of response to
      treatment with reduction in the extent of primary and regional metastases.
      Neoadjuvant chemotherapy for operable breast cancer is used in women who desire
      breast conservation surgery who are not candidates for such treatment at the time
      of the diagnosis. The use of neoadjuvant treatment in patients, who present with
      operable breast cancer, shows equivalent survival outcome compared with adjuvant
      breast cancer treatment. Several prospective studies have evaluated the role of
      trastuzumab in combination with neoadjuvant chemotherapy in patients with Her2
      positive disease. The addition of trastuzumab to neoadjuvant chemotherapy is
      associated with improvement of the complete clinical and pathological complete
      response to therapy and significantly improved event-free survival and overall
      survival. Dual Her2 blockade is emerging as a new approach to improve
      pathological complete response rates and therefore survival. To date, in triple
      negative breast cancer, there are no predictive markers to identify potential
      treatment targets. Triple-negative patients who achieve a pathological complete
      response have more favorable outcome compared with those with residual disease
      following neoadjuvant treatment. The choice of optimal chemotherapy regimen and
      the duration of treatment have been studied extensively in the neoadjuvant
      setting. No consensus has been developed thus far. Following work done with
      anthracycline and CMF treatments in neoadjuvant chemotherapy, recent studies in
      locally advanced breast cancer focus on the addition of new and target agents.
      All of these trials are based on well-established regimes used in the adjuvant
      setting. Successful use of neoadjuvant chemotherapy requires a coordinated
      multidisciplinary approach.

PMID- 24306812
TI  - A leap of faith in antidepressant treatment?

PMID- 24306813
TI  - Antidepressant medication and spontaneous abortion: "no significant association"?
      Clinically significant association!

PMID- 24306814
TI  - Developmental mismatch: why some immigrants seem protected from affective,
      personality, and substance use disorders.

PMID- 24306816
TI  - Toward a genuinely patient-centered metric of depression recovery: one step
      further.

PMID- 24306817
TI  - Diagnostic value of abdominal drainage in individual risk assessment of
      pancreatic fistula following pancreaticoduodenectomy.
AB  - BACKGROUND: The use of prophylactic abdominal drainage following
      pancreaticoduodenectomy (PD) is controversial as its therapeutic value is
      uncertain. However, the diagnosis of postoperative pancreatic fistula (POPF), the
      main cause of PD-associated morbidity, is often based on drain pancreatic amylase
      (DPA) levels. The aim of this study was to assess the predictive value of DPA,
      plasma pancreatic amylase (PPA) and serum C-reactive protein (CRP) for diagnosing
      POPF after PD. METHODS: Patients undergoing PD with prophylactic drainage between
      2008 and 2012 were studied prospectively. DPA, PPA and CRP levels were obtained
      daily. Differences between groups with clinically relevant POPF (International
      Study Group on Pancreatic Fistula (ISGPF) grade B/C) and without clinically
      relevant POPF (no POPF or ISGPF grade A) were evaluated. Receiver operating
      characteristic (ROC) analyses were performed to determine the value of DPA, PPA
      and CRP in prediction of POPF. Risk profiles for clinically relevant POPF were
      constructed and related to the intraoperative pancreatic risk assessment.
      RESULTS: Fifty-nine (18.7 per cent) of 315 patients developed clinically relevant
      POPF. DPA, PPA and CRP levels on postoperative day (POD) 1-3 differed
      significantly between the study groups. In predicting POPF, the DPA level on POD
      1 (cut-off at 1322 units/l; odds ratio (OR) 24.61, 95 per cent confidence
      interval 11.55 to 52.42) and POD 2 (cut-off at 314 units/l; OR 35.45, 14.07 to
      89.33) was superior to that of PPA on POD 1 (cut-off at 177 units/l; OR 13.67,
      6.46 to 28.94) and POD 2 (cut-off at 98 units/l; OR 16.97, 8.33 to 34.59). When
      DPA was combined with CRP (cut-off on POD 3 at 202 mg/l; OR 16.98, 8.43 to
      34.21), 90.3 per cent of postoperative courses could be predicted correctly (OR
      44.14, 16.89 to 115.38). CONCLUSION: The combination of serum CRP and DPA
      adequately predicted the development of clinically relevant pancreatic fistula
      following PD.

PMID- 24306818
TI  - Bioethics consultation practices and procedures: a survey of a large Canadian
      community of practice.
AB  - The literature fails to reflect general agreement over the nature of the services
      and procedures provided by bioethicists, and the training and core competencies
      this work requires. If bioethicists are to define their activities in a
      consistent way, it makes sense to look for common ground in shared communities of
      practice. We report results of a survey of the services and procedures among
      bioethicists affiliated with the University of Toronto Joint Centre for Bioethics
      (JCB). This is the largest group of bioethicists working in healthcare
      organizations in Canada. The results suggest there are many common services and
      procedures of JCB bioethicists. This survey can serve as a baseline for further
      exploration of the work of JCB bioethicists. Common practices exist with respect
      to the domains of practice, individual reporting relationships, service
      availability within business hours and the education and training of the
      bioethicist. 

PMID- 24306819
TI  - Facility-level analysis of PET scanning for staging among US veterans with non
      small cell lung cancer.
AB  - BACKGROUND: PET scanning has been shown in randomized trials to reduce the
      frequency of surgery without cure among patients with potentially resectable non
      small cell lung cancer (NSCLC). We examined whether more frequent use of PET
      scanning at the facility level improves survival among patients with NSCLC in
      real-world practice. METHODS: In this prospective cohort study of 622 US veterans
      with newly diagnosed NSCLC, we compared groups defined by the frequency of PET
      scan use measured at the facility level and categorized as low (<25%), medium
      (25%-60%), or high (>60%). RESULTS: The median age of the sample was 69 years.
      Ninety-eight percent were men, 36% were Hispanic or nonwhite, and 54% had
      moderate or severe comorbidities. At low-, medium-, and high-use facilities, PET
      scan was performed in 13%, 40%, and 72% of patients, respectively (P<.0001).
      Baseline characteristics were similar across groups, including clinical stage
      based on CT scanning. More frequent use of PET scanning was associated with more
      frequent invasive staging (P<.001) and nonsignificant improvements in downstaging
      (P=.13) and surgery without cure (P=.12). After a median of 352 days of follow
      up, 22% of the sample was still alive, including 22% at low- and medium-use
      facilities and 20% at high-use facilities. After adjustment and compared with
      patients at low-use facilities, the hazard of death was greater for patients at
      high-use facilities (adjusted hazard ratio [HR], 1.35; 95% CI, 1.05-1.74) but not
      different for patients at medium-use facilities (adjusted HR, 1.14; 95% CI, 0.88
      1.46). CONCLUSIONS: In this study of veterans with NSCLC, markedly greater use of
      PET scanning at the facility level was associated with more frequent use of
      invasive staging and possible improvements in downstaging and surgery without
      cure, but greater use of PET scanning was not associated with better survival.

PMID- 24306820
TI  - In case of obesity, longevity-related mechanisms lead to anti-inflammation.
AB  - The exact mechanisms which contribute to longevity have not been figured out yet.
      Our aim was to find out a common way for prompting longevity by bringing together
      the well-known applications such as food restriction, exercise, and probiotic
      supplementing in an experimental obesity model. Experimental obesity was promoted
      in a total of 32 young (2 months old) and 32 aged (16 months old) male Wistar
      albino rats through 8-week cafeteria diet (salami, chocolate, chips, and
      biscuits). Old and young animals were divided into groups each consisting of
      eight animals and also divided into four subgroups as obese control, obese food
      restriction, obese probiotic-fed and obese exercise groups. Probiotic group diet
      contained 0.05 %w/total diet inactive and lyophilized Lactobacillus casei str.
      Shirota. The exercise group was subjected to treadmill running 1 h/day, at 21
      m/min and at an uphill incline of 15 % for 5 days a week. Food restriction group
      was formed by giving 40 % less food than the others. The control group was fed
      regular pellet feed ad libitum. This program was continued for 16 weeks. Blood
      samples from all the groups were analyzed for fasting glucose, insulin, IGF-1,
      insulin-like growth factor binding protein 3 (IGFBP-3), interleukin (IL)-6, IL
      12, malondialdehyde (MDA), fT3, TT3, fT4, TT4, and liver tissue MDA levels were
      measured. All applications showed anti-inflammatory effects through the observed
      changes in the levels of IGFBP-3, IL-6, and IL-12 in the young and old obese
      rats. While the interventions normally contribute to longevity by recruiting
      different action mechanisms, anti-inflammatory effect is the only mode of action
      for all the applications in the obesity model. 

PMID- 24306823
TI  - Two old men and a youngster.

PMID- 24306821
TI  - Functional long-term results after rectal cancer surgery--technique of the
      athermal mesorectal excision.
AB  - PURPOSE: The total mesorectal excision (TME), embedded in a multimodal
      therapeutic concept, is accepted as the standard therapy of the advanced
      adenocarcinoma of the middle and lower thirds. The thermal damages of the
      autonomous nerves in the little pelvis caused by dissection devices remains a
      large problem. For our patients, we use water-jet dissection (WJD)-aided TME with
      the intention to minimise the rate of bladder and sexual function disorders.
      METHODS: From October 2001 until June 2010, we recorded 125 patients with an
      adenocarcinoma of the middle and lower third of the rectum. Ninety deep anterior
      rectum resections and 35 abdominoperineal rectum extirpations by WJD were
      performed. Of the patients, 27.2 % received neoadjuvant radiochemotherapy.
      Bladder and sexual function disorders were assessed by International Prostate
      Symptom Score and International Index of Erectile Function. RESULTS: The median
      follow-up period was 46 (2-117) months. Considering a local recurrence rate of
      9.6 %, the tumour-specific 5-year survival of the entire collective was 75.4 %.
      Long-term bladder function disorders showed in 6.0 % (4/64) and sexual function
      disorders in 25.0 % (9/36) of the male patients in the course of time.
      CONCLUSION: The specific advantage of the WJD technique is not only the
      facilitated dissection between the mesorectal fascia and the surrounding nervous
      structures in the little pelvis but also a completely athermal TME. The rate of
      bladder and sexual function disorders is an excellent result compared to that of
      international centres. Due to the size of the patient collective and the
      retrospective character of the study, further studies are necessary to validate
      the presented results.

PMID- 24306822
TI  - Nerve supply to the internal anal sphincter differs from that to the distal
      rectum: an immunohistochemical study of cadavers.
AB  - PURPOSE: Fecal incontinence is a common problem after anal sphincter-preserving
      operations. The intersphincteric autonomic nerves supplying the internal anal
      sphincter (IAS) are formed by the union of: (1) nerve fibers from Auerbach's
      nerve plexus of the most distal part of the rectum and (2) the inferior rectal
      branches of the pelvic plexus (IRB-PX) running along the conjoint longitudinal
      muscle coat. The aim of the present study is to identify the detailed morphology
      of nerves to the IAS. METHODS: The study comprised histological and
      immunohistochemical evaluations of paraffin-embedded sections from a large block
      of anal canal from the preserved 10 cadavers. RESULTS: The IRB-PX came from the
      superior aspect of the levator ani and ran into the anal canal on the
      anterolateral side. These nerves contained both sympathetic and parasympathetic
      fibers, but the sympathetic content was much higher than in nerves from the
      distal rectum. All intramural ganglion cells in the distal rectum were neuronal
      nitric oxide synthase-positive and tyrosine hydroxylase-negative and were
      restricted to above the squamous-columnar epithelial junction. Parasympathetic
      nerves formed a lattice-like plexus in the circular smooth muscles of the distal
      rectum, whereas the IAS contained short, longitudinally running sympathetic and
      parasympathetic nerves, although sympathetic nerves were dominant. CONCLUSIONS:
      The major autonomic nerve input to the IAS seemed not to originate from the
      distal rectum but from the IRB-PX. Injury to the IRB-PX during surgery seemed to
      result in loss of innervation to the major part of the IAS.

PMID- 24306824
TI  - "Allocation of medical resources".
AB  - Typical macroallocation and microallocation paradigms of medical resources are
      discussed. Rather than strict polarization of these two aspects of resource
      allocation, a spectrum of positions is emphasized that supports approaching both
      extremes in the same fashion. Until now many have argued for a social value
      oriented system for macroallocation issues while choosing randomness or queuing
      for the opposite extreme. I do not believe that such a distinction can be morally
      supported but that a consistent approach to allocation of resources should be
      maintained. 

PMID- 24306825
TI  - Spiritual growth through care of the dying.
AB  - One of the most difficult issues with which clergy must deal is that of theodicy,
      the reconciliation of a good God with evil in this world. The case of L.R. is
      that of a good thirty-nine-year-old man dying of cancer. This paper examines the
      role of the clergy in working with the dying patient, traditional responses to
      the questions of theodicy, and a proposal for an adequate contemporary solution
      to the issue of theodicy. One key factor in caring for the dying is the mutual
      spiritual growth of the dying patient and the clergy care giver. 

PMID- 24306826
TI  - Chaplains' medical approach to psychiatric patients.
AB  - Chaplains' understanding of people's psychiatric and medical problems may aid
      them in dealing with people's spiritual problems. However, exploratory interviews
      and observations of chaplains and inpatients at a VA psychiatric facility
      indicate that chaplains take a medical model perspective with patients, often
      attempting to treat patients' psychiatric problems rather than focusing on their
      reliigious needs. Chaplains avoid one-on-one religious discussions despite the
      importance of these conversations to patients. Discussed are implications for the
      utilization of health services and for the formation of treatment teams. 

PMID- 24306827
TI  - Philosophy in religious health care facilities.
AB  - Why formulate a philosophy statement? How may this statement influence
      organizational life? Answers to these questions affirm the practical utility of a
      philosophy within a health care facility. In addressing the first question,
      consideration is given to the philosophical questions by whom, to whom, and for
      what purpose is the organization sent. Also considered are its purpose in
      relating to and mode of relating to its patients. The practical place of a
      philosophy is illustrated through the difference between for-profit and non
      profit corporations. A close analysis of organizational structure, systems, and
      strategies details this difference. 

PMID- 24306828
TI  - The development of medical sects.
AB  - There exist a number of studies that demonstrate a parallel between secular and
      transcendental movements. A useful exercise is to look at the development of
      medicine and compare the origin and development of medical sects with sects that
      we would more normally associate with religious development. Thus, the struggle
      for a dominant ideology in medicine meant that Galenism as the New Systematists
      gave way to the emergence of a dominant medical orthodoxy. The dilemmas presented
      by new discoveries in medicine highlight this struggle for dominance. Running
      alongside medical sectarianism is the phenomenon of medical cults such as
      phrenology and mesmerism. Osteopathy, naturopathy, homeopathy, and chiropractic
      are significant examples of modern challenges to the monopoly of medical
      knowledge exhibited by sects. 

PMID- 24306830
TI  - Time in the dream.
AB  - Therapies that make use of dream material tend to interpret in the past, present,
      or future tense. Representative therapies that emphasize each tense are reviewd
      to motivate the notion of interpreting in all three tenses. The potential for
      integration over past, present, and future is discussed, and a detailed
      illustration is presented. 

PMID- 24306829
TI  - The role of religious values in coping with cancer.
AB  - The relationship between transcendent meaning attribution, religious orientation,
      and psychological well-being was studied in cancer and noncancer patients to test
      the hypotheses that intrinsic religious values and life meaning enhance coping
      and well-being during the course of the life-threatening illness. Subjects were
      44 patients receiving medical treatment for cancer and noncancer medical
      conditions. In the cancer group, higher levels of attributed life meaning were
      positively linked with intrinsic religious orientation, and associated with lower
      levels of despiar, anger-hostility, and social isolation. Cancer patients scored
      higher than noncancer patients on depersonalization, suggesting the presence of
      psychic numbing in response to their illness. Noncancer group results were
      characterized by positive correlations between the two groups in coping styles
      and salience of life meaning attribution. A rationale for the observed
      differences in coping styles between the two groups is presented, highlighting
      perceived life threat as a key differentiating variable. 

PMID- 24306831
TI  - The temporal scaling of bacterioplankton composition: high turnover and
      predictability during shrimp cultivation.
AB  - The spatial distribution of microbial communities has recently been reliably
      documented in the form of a distance-similarity decay relationship. In contrast,
      temporal scaling, the pattern defined by the microbial similarity-time
      relationships (STRs), has received far less attention. As a result, it is unclear
      whether the spatial and temporal variations of microbial communities share a
      similar power law. In this study, we applied the 454 pyrosequencing technique to
      investigate temporal scaling in patterns of bacterioplankton community dynamics
      during the process of shrimp culture. Our results showed that the similarities
      decreased significantly (P = 0.002) with time during the period over which the
      bacterioplankton community was monitored, with a scaling exponent of w = 0.400.
      However, the diversities did not change dramatically. The community dynamics
      followed a gradual process of succession relative to the parent communities, with
      greater similarities between samples from consecutive sampling points. In
      particular, the variations of the bacterial communities from different ponds
      shared similar successional trajectories, suggesting that bacterial temporal
      dynamics are predictable to a certain extent. Changes in bacterial community
      structure were significantly correlated with the combination of Chl a, TN, PO4 (3
      ), and the C/N ratio. In this study, we identified predictable patterns in the
      temporal dynamics of bacterioplankton community structure, demonstrating that the
      STR of the bacterial community mirrors the spatial distance-similarity decay
      model.

PMID- 24306832
TI  - Characteristics of community health organizations and decision-makers considering
      the adoption of motivational interviewing.
AB  - Research related to the adoption of comparative effectiveness research (CER) in
      mental health practice is limited. This study explores the factors that influence
      decisions to adopt motivational interviewing (MI)-an evidence-based practice
      (EBP) grounded in CER-among decision-makers (n = 311) in community health
      organizations (n = 92). Descriptive analyses focus on organization and decision
      maker characteristics and processes that may influence the decision to adopt an
      EBP, including demographics, structure and operations, readiness, attitudes,
      barriers, and facilitators. Within-group agreement is examined to determine the
      degree to which participants within each organization gave similar responses.
      Results show characteristics differed according to type of organization
      (community health versus community behavioral health) and position (directors
      versus staff). Within-group agreement was also influenced by position. These
      findings indicate different strategies may be needed to best disseminate CER to
      the two groups.

PMID- 24306833
TI  - Sleep disturbance in adolescents: Sleep quality, sleep habits, beliefs about
      sleep, and daytime functioning.
AB  - This study examined the prevalence and correlates of sleep disturbance in
      adolescents. Two hundred seventy-seven 9th- and 10th-grade students completed a
      questionnaire on sleep quality, sleep habits, beliefs about sleep, and daytime
      mood and functioning. Based on their responses, subjects were classified as good
      sleepers (66%), occasional poor sleepers (23%), and chronic poor sleepers (11%).
      Occasional and chronic poor sleepers reported being significantly more depressed,
      without energy, tense, moody, and irritable and less rested and alert than good
      sleepers. They were also more likely to describe themselves negatively. However,
      poor sleepers were not consistently more tired than good sleepers. Rather, they
      tended to be least tired in the evening, the time when most good sleepers
      reported feeling tired. There were few differences in the sleep habits and
      beliefs about sleep of good and poor sleepers. All subjects reported shifts in
      bedtimes and waketimes from weekdays to weekends, with occasional and chronic
      poor sleepers showing a tendency toward greater shifts, a possible factor
      contributing to their sleep disturbance. Occasional and chronic poor sleepers
      also reported more observable behaviors and feelings of stress than good
      sleepers. The need for early intervention with particular attention to teaching
      adolescents about good sleep habits and the need for stable bedtimes and
      waketimes and the possibility of joint intervention on daytime stress and
      sleeping problems are discussed. 

PMID- 24306834
TI  - Sex in transition, 1900-1980.
AB  - Changes in the proportion of college-aged males and females participating in
      coital relationships are analyzed through a review of 35 studies conducted
      between 1903 and 1980. Two major trends are apparent: there has been a major
      increase in the proportion of young people reporting intercourse, and the
      proportion of females reporting coital involvement has increased more rapidly
      than the proportion of males, although the initial base for males is greater.
      Prior to 1970, about twice as many college men as women reported having had
      intercourse; since 1970, the proportions of men and women reporting coital
      involvement are nearly equal. These changes are seen as supportive of major
      shifts in the standards governing sexual behavior from the double standard to the
      single standard of permissiveness with affection [Reiss, I. F. (1967).The Social
      Context of Premarital Sexual Permissiveness, Rinehart and Winston, New York] to
      the current standard of intercourse being appropriate in love relationships
      (without the requirement of progression toward marriage) and permissible in
      causal relationships without exploitation. 

PMID- 24306835
TI  - Adolescent egocentrism: The association among imaginary audience behavior,
      cognitive development, and parental support and rejection.
AB  - Two theoretical perspectives have been advanced to account for heightened
      egocentrism during early adolescence. One perspective assumes that formal
      operational thought is associated with increased self-consciousness. The second
      perspective proposes that parental support and affection diminish egocentrism,
      while parental rejection enhances self-conscious reactions by young adolescents.
      Data analysis using responses from 251 early adolescents (131 males, 120 females)
      on measures of cognitive development and perceived parental support revealed that
      (a) formal operations diminished adolescent egocentrism, while (b) perceived
      parental relations were predictive of self-consciousness. Contrary to
      posttheoretical assumptions, seventh graders functioning at the level of concrete
      operations were higher in self-conscious egocentrism than were formal-operations
      youths. Further, perceived parental support was associated with diminished
      egocentrism, while perceived parental rejection was predictive of heightened self
      consciousness. 

PMID- 24306836
TI  - Development of an objective measure to assess ego identity in adolescence:
      Validation and replication.
AB  - Three studies that evaluate the reliability and validity of the Extended Version
      of the Objective Measure of Ego Identity Status (Adams and Grotevant, 1983) are
      reported. In Studies 1 and 2, college students in Texas and Utah, respectively,
      completed the identity measure, the Extended Range Vocabulary Test, and the
      Crowne-Marlowe Social Desirability Scale and released achievement results from
      their college records. The identity measure was found to have acceptable
      reliability (both internal consistency and test-retest) and validity (content,
      factorial, discriminant, and concurrent). In Study 3, scale scores from the
      objective identity measure correlated in the predicted pattern with ratings of
      identity exploration and commitment made from the Ego Identity Interview.
      Although the objective measure is not intended to replace the interview, it would
      appear to be useful in a number of situations where administration of the
      interview is impractical. 

PMID- 24306837
TI  - Physical attractiveness as a mediator of the impact of early pubertal changes for
      girls.
AB  - The present study examined the effects of early pubertal development and physical
      attractiveness on the popularity, body image, and self-esteem of over 200 sixth
      grade girls. Two rival hypotheses were explored. The first suggests that
      physically attractive girls, because of their more favorable social environment,
      will exhibit fewer psychosocial difficulties than unattractive girls during
      pubertal development. The second hypothesis argues that attractive girls will
      exhibit greater difficulty during pubertal transition because their self-image is
      more intimately connected with their physical appearance. Although there were no
      significant interactions between attractiveness and pubertal development for
      either popularity or body image, the second hypothesis was supported with respect
      to self-esteem. Specifically, developing attractive girls exhibited lower self
      esteem than their unattractive counterparts. The results are discussed in terms
      of the relative vulnerability to bodily changes of girls differing in physical
      attractiveness. 

PMID- 24306838
TI  - Delinquent recidivists: Vulnerable children.
AB  - This study examines the relationship between vulnerability factors and recidivism
      by testing the hypothesis that first offenders who repeat delinquencies display
      more high-risk factors than those who do not repeat delinquencies. Four factors
      are identified which distinguish recidivists from nonrecidivists in a sample of
      first offenders matched by age and sex. Results are discussed from an
      epidemiological and early-intervention perspective. 

PMID- 24306839
TI  - [Systemic sclerosis and pregnancy. A review of the current literature].
AB  - Pregnancy in women diagnosed with systemic sclerosis generally has a favorable
      outcome according to most recent studies. Women with systemic sclerosis who wish
      to become pregnant should achieve low disease activity for at least 6 months
      prior to conception. Regular follow-up of pregnant scleroderma patients by an
      interdisciplinary medical team including gynaecologists and rheumatologists is
      necessary to control disease activity and avoid possible complications. Severe
      organ involvement, early diffuse systemic sclerosis with rapid onset, and
      pulmonary hypertension ought to discourage patients from pregnancy, as these
      situations are at high risk of complications for both mother and fetus during
      pregnancy. 

PMID- 24306840
TI  - [Incidence rates and risk factors for gastrointestinal perforation in patients
      with rheumatoid arthritis].

PMID- 24306841
TI  - The discovery and function of plastocyanin: A personal account.
AB  - A brief autobiographical account is presented of the early research that led to
      the discovery of the copper protein plastocyanin and the identification of its
      function as an electron carrier in plant photosynthesis. A discussion follows of
      different approaches employed for the determination of the functional site of
      plastocyanin in relation to cytochrome f. A summary is provided of a heated
      controversy about the involvement of two or three light reactions in
      photosynthesis and an experiment is described that has contributed to resolution
      of the controversy through the identification of the functional site of
      plastocyanin. An early history of photosynthesis research in Japan is also
      discussed. 

PMID- 24306842
TI  - Effects of hydrostatic pressure on the kinetics of electron transfer in an
      isolated system of chloroplast cytochrome bf complex, plastocyanin and P700.
AB  - The effects of pressure on the kinetics of redox reactions in and around the
      chloroplast cytochrome bf complex were studied using a reconstituted system
      consisting of Photosystem I (PS I) particles, cytochrome bf complex and
      plastocyanin (PC), all derived from pea chloroplasts. There were no significant
      permanent effects of pressure in the range 0.1-191 MPa on the reaction kinetics,
      or on the shape of the absorption spectra of components studied. Discernable
      effects on rate-coefficients of increasing pressure were observed on the
      reduction of P700(+) by PC(I), on the reduction of PC(II) by ascorbate, and on
      the oxidation of decyl plastoquinol by the bf complex. The volumes of activation
      DeltaV(#) were determined from the dependence of the rate-coefficient on pressure
      using: [Formula: see text] The volume of activation is the difference in partial
      molar volume between the activated state and the reactants for the redox
      reaction. Such data was sought to help define in detail those redox reactions and
      the corresponding activated states. For the reduction of P700(+) by PC(I) and the
      oxidation of decyl plastoquinol by the bf complex, the rate coefficient decreased
      with increase in pressure, whilst for the reduction of PC(II) by ascorbate it
      increased. The corresponding volumes of activation were 9.6+/-0.6*10(-6) m(3)
      mol(-1), 18+/-2*10(-6) m(3) mol(-1) and -14+/-1*10(-6) m(3) mol(-1),
      respectively. Much of the pressure-dependence of PC(II) reduction by ascorbate
      was ascribed to an increase in ascorbate ionisation with increase in pressure.
      There was little effect of pressure on the kinetics of oxidation of
      ferrocytochrome f by PC(II), or on the equilibrium constant of the redox pair
      ferrocytochrome f/ferricytochrome f: PC(II)/PC(I). Possible physical bases for
      these activation volumes are discussed, and they are compared with literature
      values. 

PMID- 24306843
TI  - Purification of a Photosystem II reaction center from a thermophilic
      cyanobacterium using immobilized metal affinity chromatography.
AB  - Oxygen-evolving PS II particles from the thermophilic cyanobacterium
      Synechococcus elongatus are partially purified by centrifugation on a sucrose
      gradient and are bound to a Chelating Sepharose column loaded with Cu(2+) ions.
      Bound particles are then transformed into PS II RC complexes by two washing
      steps. First, washing with a phosphate buffer (pH=6.5) containing 0.02% of SB 12
      removes the rest of phycobilins and leaves pure PS II core particles on the
      column. Second, washing with a phosphate buffer (pH=6.2) containing 0.2 M LiClO4
      and 0.05% of DM removes CP 47 and CP 43 and leaves bare PS II RC complexes on the
      column. These are then eluted with a phosphate buffer containing 1% of
      dodecylmaltoside (DM). The molar ratio of pigments in the eluate changes with the
      progress of elution but around the middle of the elution period a nearly stable
      ratio is maintained of Chl a: Pheo a: Car: Cyt b 559 equal to 2.9: 1: 0.9: 0.8.
      In these fractions the photochemical separation of charges could be demonstrated
      by accumulation of reduced pheophytin (DeltaA of 430-440 nm) and by the flash
      induced formation of P680(+) (DeltaA at 820 nm). The relatively slow relaxation
      kinetics of the latter signal (t1/2 ~ 1 ms) may suggest that in a substantial
      fraction of the RCs QA remains bound to the complex. 

PMID- 24306844
TI  - Rubisco, rubisco activase and ribulose-5-phosphate kinase gene expression and
      polypeptide accumulation in a tobacco mutant defective in chloroplast protein
      synthesis.
AB  - Expression of the genes for ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco; rbcS and rbcL), Rubisco activase (rca) and ribulose-5-phosphate (Ru5-P)
      kinase (prk) and accumulation of the polypeptides was examined in chlorophyllous
      and chlorotic sectors of the DP1 mutant of Nicotiana tabacum. Plastids from
      chlorotic sectors of this variegated plastome mutant contained 30S and 50S
      ribosomal subunits, but had abnormally low levels of plastid polysomes.
      Consequently, mutant plastids were translationally repressed, unable to
      synthesize plastid-encoded polypeptides including the large subunit of Rubisco
      despite the presence of the corresponding mRNAs. Transcripts of rbcS accumulated
      to near wild type levels in chlorotic sectors, but there was little accumulation
      of the Rubisco small subunit (SS) polypeptide or holoenzyme. Messenger-RNA
      isolated from chlorotic sectors effectively directed the synthesis of Rubisco SS
      in vitro suggesting that posttranslational factors were responsible for the
      decrease in Rubisco SS abundance. Transcripts of rca and prk also accumulated to
      near wild type levels in chlorotic sectors and a diurnal rhythm in the abundance
      of rca mRNA was detected in green and chlorotic sectors. Despite the low
      abundance of Rubisco holoenzyme in chlorotic sectors, Rubisco activase and Ru5-P
      kinase polypeptides accumulated to significant levels. Activities of Rubisco and
      Ru5-P kinase paralleled protein levels, indicating that active forms of these
      enzymes were present in chlorotic sectors. The data indicate that the
      developmental events governing the accumulation of Rubisco activase and Ru5-P
      kinase polypeptides and the diurnal regulation of rca expression were not
      dependent on the attainment of photosynthetically competent plastids or the
      accumulation of Rubisco. 

PMID- 24306845
TI  - Changes in lipid composition of Photosystem 1 particles from thylakoids
      phosphorylated under reductive or anaerobic conditions.
AB  - Changes in lipid composition of Photosystem 1 (PS 1) particles isolated from
      thylakoids phosphorylated under reductive or anaerobic conditions have been
      studied. Under reductive conditions, there was an increase in
      monogalactosyldiacylglycerol containing highly saturated fatty acids and
      phosphatidylglycerol containing transhexadecenoic fatty acid. Under anaerobic
      conditions, the amount of all lipid classes was increased. As we have shown
      earlier (S. V. Manuilskaya, O. I. Volovik, A. I. Mikhno, A. I. Polischuk and S.
      M. Kochubey (1990) Photosynthetica 24: 419-423) these changes were due to a co
      migration of some lipid species and light-harvesting chlorophyll a/b complex LHC
      II from PS 2 to PS 1. These data allow us to conclude that LHC II consists of the
      lipoproteins containing specific lipids. Different composition of lipids co
      migrating with LHC II under various conditions of phosphorylation might be caused
      by the variety of LHC II subpopulations transferred under each reductive
      condition. 

PMID- 24306846
TI  - A 64-kDa protein is a substrate for phosphorylation by a distinct thylakoid
      protein kinase.
AB  - Solubilization of spinach thylakoids with the nonionic detergent n-octyl-beta-D
      glucopyranoside (OG) releases active protein kinase from the membrane. Further
      purification was reported to demonstrate that a 64-kDa protein is the origin of
      this kinase activity (Coughlan S J and Hind G (1986) J Biol Chem 261: 11378
      11385). The N-terminal sequence of this protein was subsequently determined (Gal
      A, Herrmann R, Lottspiech F and Ohad I (1992) FEBS Lett 298: 33-35). Liquid phase
      isoelectric focusing of the OG extract and an hydroxylapatite-purified fraction,
      derived from the OG preparation, reveals that the 64-kDa protein with this
      documented N-terminal sequence can be separated from the protein kinase activity.
      Experimental conditions were optimised by manipulation of ampholyte and detergent
      concentrations to maximise protein solubility and enzyme activity. The kinase
      containing fraction was able to catalyze the phosphorylation of several proteins
      including the 64-kDa which was identified using antibodies raised against a
      synthetic peptide corresponding to the N-terminal sequence. The results described
      indicate that this 64-kDa protein is not the protein kinase responsible for the
      phosphorylation of the light-harvesting complex associated with Photosystem II. 

PMID- 24306847
TI  - Thylakoid-bound proteolytic activity against LHC II apoprotein in bean.
AB  - Triton X-100 solubilized thylakoids, isolated from Phaseolus vulgaris
      chloroplasts, degrade endogenous or exogenously added LHC II. The degradation, as
      monitored by immunodetection of the remaining LHC II after incubation at 37
      degrees C, is activated by Mg(++) and inhibited by pCMB, EDTA, PMSF and
      benzamidine; the activity under high light conditions parallels chlorophyll
      photooxidation. The thylakoid-bound proteolytic activity is under phytochrome
      control. Etiolated plants pretreated by a white light pulse, and kept in the dark
      thereafter, show enhanced proteolytic activity, which follows rhythmical
      oscillations. On the other hand, chloramphenicol pretreatment of etiolated
      plants, prior to their transfer to continuous light, reduces the proteolytic
      activity against LHC II. The results suggest that the degradation involves a
      serine type protease, which depends on SH group(s), coded by the plastid genome;
      the protease action on LHC II is regulated by Mg(++), phytochrome, the biological
      clock and chlorophyll accumulation in the thylakoid. The stroma lamellar
      fraction, separated from French press disrupted chloroplasts, exhibits higher
      activity towards exogenous LHC II than the grana fraction. The stroma of intact
      chloroplasts exhibits also high proteolytic activity, which is drastically
      reduced when the lysis medium is supplemented with cations. This suggests that
      the protease is bound mainly on stroma lamellae and peripheral granal membranes,
      its association to the membranes being possibly under cation control. 

PMID- 24306848
TI  - Effects of dark- and light-induced proton gradients in thylakoids on the Q and B
      thermoluminescence bands.
AB  - Thermoluminescence experiments have been carried out to study the effect of a
      transmembrane proton gradient on the recombination properties of the S2 and S3
      states of the oxygen evolving complex with QA (-) and QB (-), the reduced
      electron acceptors of Photosystem II. We first determined the properties of the
      S2QA (-) (Q band), S2QB (-) and S3QB (-) (B bands) recombinations in the pH range
      5.5 to 9.0, using uncoupled thylakoids. The, a proton gradient was created in the
      dark, using the ATP-hydrolase function of ATPases, in coupled unfrozen
      thylakoids. A shift towards low temperature of both Q and B bands was observed to
      increase with the magnitude of the proton gradient measured by the fluorescence
      quenching of 9-aminoacridine. This downshift was larger for S3QB (-) than for
      S2QB (-) and it was suppressed by nigericin, but not by valinomycin. Similar
      results were obtained when a proton gradient was formed by photosystem I
      photochemistry. When Photosystem II electron transfer was induced by a flash
      sequence, the reduction of the plastoquinone pool also contributed to the
      downshift in the absence of an electron acceptor. In leaves submitted to a flash
      sequence above 0 degrees C, a downshift was also observed, which was supressed by
      nigericin infiltration. Thus, thermoluminescence provides direct evidence on the
      enhancing effect of lumen acidification on the S3->S2 and S2->S1 reverse
      transitions. Both reduction of the plastoquinone pool and lumen acidification
      induce a shift of the Q and B bands to lower temperature, with a predominance of
      lumen acidification in non-freezing, moderate light conditions. 

PMID- 24306849
TI  - Contrasting leaf and 'ecosystem' CO2 and H 2O exchange in Avena fatua
      monoculture: Growth at ambient and elevated CO2.
AB  - Elevated CO2 (ambient + 35 Pa) increased shoot dry mass production in Avena fatua
      by ~ 68% at maturity. This increase in shoot biomass was paralleled by an 81%
      increase in average net CO2 uptake (A) per unit of leaf area and a 65% increase
      in average A at the 'ecosystem' level per unit of ground area. Elevated CO2 also
      increased 'ecosystem' A per unit of biomass. However, the products of total leaf
      area and light-saturated leaf A divided by the ground surface area over time
      appeared to lie on a single response curve for both CO2 treatments. The
      approximate slope of the response suggests that the integrated light saturated
      capacity for leaf photosynthesis is ~ 10-fold greater than the 'ecosystem' rate.
      'Ecosystem' respiration (night) per unit of ground area, which includes soil and
      plant respiration, ranged from-20 (at day 19) to-18 (at day 40) MUmol m(-2) s(-1)
      for both elevated and ambient CO2 Avena. 'Ecosystem' below-ground respiration at
      the time of seedling emergence was ~-10 MUmol m(-2) s(-1), while that occuring
      after shoot removal at the termination of the experiment ranged from -5 to-6
      MUmol m(-2) s(-1). Hence, no significant differences between elevated and ambient
      CO2 treatments were found in any respiration measure on a ground area basis,
      though 'ecosystem' respiration on a shoot biomass basis was clearly reduced by
      elevated CO2. Significant differences existed between leaf and 'ecosystem' water
      flux. In general, leaf transpiration (E) decreased over the course of the
      experiment, possibly in response to leaf aging, while 'ecosystem' rates of
      evapotranspiration (ET) remained constant, probably because falling leaf rates
      were offset by an increasing total leaf biomass. Transpiration was lower in
      plants grown at elevated CO2, though variation was high because of variability in
      leaf age and ambient light conditions and differences were not significant. In
      contrast, 'ecosystem' evapotranspiration (ET) was significantly decreased by
      elevated CO2 on 5 out of 8 measurement dates. Photosynthetic water use
      efficiencies (A/E at the leaf level, A/ET at the 'ecosystem' level) were
      increased by elevated CO2. Increases were due to both increased A at leaf and
      'ecosystem' level and decreased leaf E and 'ecosystem' ET. 

PMID- 24306850
TI  - Occurrence of the carotenoid lactucaxanthin in higher plant LHC II.
AB  - The pigment composition of the light-harvesting complexes of Photosystem II (LHC
      II) has been determined for lettuce (Lactuca sativa). In common with other
      members of the composite, the photosynthetic tissues of this species may contain
      large amounts of the carotenoid lactucaxanthin (epsilon, epsilon-carotene-3,3'
      diol) in addition to their normal compliment of carotenoids. The occurrence and
      distribution of lactucaxanthin in LHC II has been examined using isoelectric
      focusing of BBY particles followed by reversed-phase HPLC analysis of the
      pigments. The major carotenoids detected in LHC IIb, LHC IIa (CP29) and LHC IIc
      (CP26) purified from dark-adapted lettuce were lutein, violaxanthin, neoxanthin
      and lactucaxanthin. Lactucaxanthin has been shown to be a major component of PS
      II, accounting for ~26% of total xanthophyll in both LHC IIb (~23% total
      xanthophyll) and in the minor complexes (12-16%). In this study, LHC IIb was
      clearly resolved into four bands and their carotenoid composition determined.
      These four bands proved to be very similar in their pigment content and
      composition, although the relative amounts of neoxanthin and lutein in particular
      were found to increase from bands 1 to 4 (i.e. with increasing electrophoretic
      mobility). The operation of the xanthophyll cycle has also been examined in the
      LHC of L. sativa following light treatment. The conversion efficiency for
      violaxanthin->zeaxanthin was nearly identical for each light-harvesting complex
      examined at 58-61%. Nearly half of the zeaxanthin formed in PS II was associated
      with LHC IIb, although the molar ratio of zeaxanthin:chlorophyll a was highest in
      the minor LHC. 

PMID- 24306851
TI  - Regulatory phosphorylation of C4 phosphoenolpyruvate carboxylase from Sorghum: An
      immunological study using specific anti-phosphorylation site-antibodies.
AB  - A peptide containing the N-terminal phosphorylation site (Ser-8) of Sorghum C4
      phospho enolpyruvate carboxylase (PEPC) was synthesized, purified and used to
      raise an antiserum in rabbits. Affinity-purified IgGs prevented PEPC
      phosphorylation in a reconstituted in vitro assay and reacted with both the
      phosphorylated and dephosphorylated forms of either native or denatured PEPC in
      immunoblotting experiments. Saturation of dephospho-PEPC with these specific IgGs
      resulted in a marked alteration of its functional and regulatory properties that
      mimicked phosphorylation of Ser-8. A series of recombinant C4 PEPCs mutated in
      the N-terminal phosphorylation domain and a C3-like PEPC isozyme from Sorghum
      behaved similarly to their C4 counterpart with respect to these phosphorylation
      site antibodies. 

PMID- 24306852
TI  - Concavities, negative parts, and the perception that shapes are complete.
AB  - When we perceive the shape of an object, we can often make many other inferences
      about the object, derived from its shape. For example, when we look at a bitten
      apple, we perceive not only the local curvatures across the surface, but also
      that the shape of the bitten region was caused by forcefully removing a piece
      from the original shape (excision), leading to a salient concavity or negative
      part in the object. However, excision is not the only possible cause of
      concavities or negative parts in objects-for example, we do not perceive the
      spaces between the fingers of a hand to have been excised. Thus, in order to
      infer excision, it is not sufficient to identify concavities in a shape; some
      additional geometrical conditions must also be satisfied. Here, we studied the
      geometrical conditions under which subjects perceived objects as been bitten, as
      opposed to complete shapes. We created 2-D shapes by intersecting pairs of
      irregular hexagons and discarding the regions of overlap. Subjects rated the
      extent to which the resulting shapes appeared to be bitten or whole on a 10-point
      scale. We find that subjects were significantly above chance at identifying
      whether shapes were bitten or whole. Despite large intersubject differences in
      overall performance, subjects were surprisingly consistent in their judgments of
      shapes that had been bitten. We measured the extent to which various geometrical
      features predict subjects' judgments and find that the impression that an object
      is bitten is strongly correlated with the relative depth of the negative part.
      Finally, we discuss the relationship between excision and other perceptual
      organization processes such modal and amodal completion, and the inference of
      other attributes of objects, such as the material properties. 

PMID- 24306853
TI  - A neural hierarchy for illusions of time: duration adaptation precedes
      multisensory integration.
AB  - Perceived time is inherently malleable. For example, adaptation to relatively
      long or short sensory events leads to a repulsive aftereffect such that
      subsequent events appear to be contracted or expanded (duration adaptation).
      Perceived visual duration can also be distorted via concurrent presentation of
      discrepant auditory durations (multisensory integration). The neural loci of both
      distortions remain unknown. In the current study we use a psychophysical approach
      to establish their relative positioning within the sensory processing hierarchy.
      We show that audiovisual integration induces marked distortions of perceived
      visual duration. We proceed to use these distorted durations as visual adapting
      stimuli yet find subsequent visual duration aftereffects to be consistent with
      physical rather than perceived visual duration. Conversely, the concurrent
      presentation of adapted auditory durations with nonadapted visual durations
      results in multisensory integration patterns consistent with perceived, rather
      than physical, auditory duration. These results demonstrate that recent sensory
      history modifies human duration perception prior to the combination of temporal
      information across sensory modalities and provides support for adaptation
      mechanisms mediated by duration selective neurons situated in early areas of the
      visual and auditory nervous system (Aubie, Sayegh, & Faure, 2012; Duysens,
      Schaafsma, & Orban, 1996; Leary, Edwards, & Rose, 2008). 

PMID- 24306854
TI  - The role of eye movements in a contour detection task.
AB  - Vision combines local feature integration with active viewing processes, such as
      eye movements, to perceive complex visual scenes. However, it is still unclear
      how these processes interact and support each other. Here, we investigated how
      the dynamics of saccadic eye movements interact with contour integration,
      focusing on situations in which contours are difficult to find or even absent. We
      recorded observers' eye movements while they searched for a contour embedded in a
      background of randomly oriented elements. Task difficulty was manipulated by
      varying the contour's path angle. An association field model of contour
      integration was employed to predict potential saccade targets by identifying
      stimulus locations with high contour salience. We found that the number and
      duration of fixations increased with the increasing path angle of the contour. In
      addition, fixation duration increased over the course of a trial, and the time
      course of saccade amplitude depended on the percept of observers. Model fitting
      revealed that saccades fully compensate for the reduced saliency of peripheral
      contour targets. Importantly, our model predicted fixation locations to a
      considerable degree, indicating that observers fixated collinear elements. These
      results show that contour integration actively guides eye movements and
      determines their spatial and temporal parameters. 

PMID- 24306855
TI  - Assessing the effectiveness of health care cost containment measures: evidence
      from the market for rehabilitation care.
AB  - This study empirically evaluates the effectiveness of different health care cost
      containment measures. The measures investigated were introduced in Germany in
      1997 to reduce moral hazard and public health expenditures in the market for
      rehabilitation care. Of the analyzed measures, doubling the daily copayments was
      clearly the most effective cost containment measure, resulting in a reduction in
      utilization of about [Formula: see text] . Indirect measures such as allowing
      employers to cut federally mandated sick pay or paid vacation during inpatient
      post-acute care stays did not significantly reduce utilization. There is evidence
      neither for adverse health effects nor for substitution effects in terms of more
      doctor visits. 

PMID- 24306856
TI  - Chemiluminescent examination of abiotic oxidative stress of watercress.
AB  - Watercress (Nasturtium officinale) is an aquatic plant that readily
      bioaccumulates heavy metals that may be found in contaminated aquatic systems.
      Toxic effects of contaminants on the physiological processes cause changes in
      oxidase enzymatic activity in watercress, which can be measured with a
      luminometer. The luminometer uses the reaction produced when peroxidases break
      down hydrogen peroxide into water and an oxygen radical. The resulting oxyradical
      binds to and oxidizes phenolic groups, producing a measureable luminescent
      reaction. Nasturtium officinale plants were exposed to 3 different concentrations
      of heavy metals, including lead, nickel, copper, and manganese for 24 h, 48 h,
      and 72 h. Aquatic exposure to the 4 heavy metals caused a significant increase in
      oxidative enzyme production. Fluorometric and morphometric measurements were also
      conducted to compare plant stress with the oxidative enzyme analyses.
      Fluorometric measurements performed on plants stressed by exposure to heavy
      metals revealed no significant decreases in photosystem II efficiency.
      Morphometric measurements of root length showed decreased root growth resulting
      from exposures to Ni, Cu, and Mn.

PMID- 24306857
TI  - Fully automated compound screening in Arabidopsis thaliana seedlings.
AB  - High-throughput small molecule screenings in model plants are of great value to
      identify compounds that interfere with plant developmental processes. In academic
      research, the plant Arabidopsis thaliana is the most commonly used model organism
      for this purpose. However, compared to plant cellular systems, A. thaliana plants
      are less amenable to develop high-throughput screening assays. In this chapter,
      we describe a screening procedure that is compatible with liquid handling systems
      and increases the throughput of compound screenings in A. thaliana seedlings. 

PMID- 24306858
TI  - Time-profiling fluorescent reporters in the Arabidopsis root.
AB  - Confocal laser scanning microscopy is a useful nondestructive approach for the
      visualization of fluorescent reporters in planta. Samples are usually placed
      between a slide and a cover slip which, although suited to single time-point
      imaging, does not allow long-term observation. Here, we describe a technique to
      monitor changes in fluorescence in the Arabidopsis root over a long period of
      time. Treatment can easily be performed, and this approach is suitable for use in
      low-throughput chemical screens. We also present a rapid method to analyze
      fluorescence intensity profiles generated using this protocol. 

PMID- 24306859
TI  - Screening for bioactive small molecules by in vivo monitoring of luciferase-based
      reporter gene expression in Arabidopsis thaliana.
AB  - Chemical genetics is a scientific strategy that utilizes bioactive small
      molecules as experimental tools to dissect biological processes. Bioactive
      compounds occurring in nature represent an enormous diversity of structures that
      potentially can be used as activators or inhibitors of biochemical pathways,
      transport processes, regulatory networks, or developmental programs. Screening
      methods to identify bioactive small molecules can vary greatly, ranging from
      visual evaluation of phenotypic alterations to quantifying biometric traits such
      as enzyme activities. Here, we describe a general methodology that permits
      identification of compounds modulating the expression of reporter genes in
      Arabidopsis thaliana seedlings. The selection of luciferase-based reporter
      systems has the advantage that it allows in vivo imaging of reporter gene
      activity in a semiquantitative manner without affecting plant viability. We chose
      an Arabidopsis line harboring the luciferase reporter under the control of the
      jasmonate-inducible LOX2 promoter to screen for either activators or inhibitors
      of gene expression. The outlined assay conditions can readily be applied to
      Arabidopsis lines containing other reporter genes. Thereby screening for small
      molecules affecting different signaling pathways and/or phenotypic responses is
      possible. 

PMID- 24306860
TI  - Application of yeast-two hybrid assay to chemical genomic screens: a high
      throughput system to identify novel molecules modulating plant hormone receptor
      complexes.
AB  - Phytohormones are endogenous signalling molecules that regulate plant
      development, adaptation to the environment, and survival. Upon internal or
      external stimuli, hormones are quickly accumulated and perceived, which in turn
      activates specific signalling cascades regulating the appropriate physiological
      responses. In the last decade, great advances in understanding plant hormone
      perception mechanisms have been achieved. Among different methodological
      approaches, yeast-two hybrid (Y2H) assays played a pivotal role in the
      identification and analysis of plant hormone perception complexes. The Y2H assay
      is a rapid and straightforward technique that can be easily employed to identify
      small molecules directly modulating plant hormone perception complexes in a high
      throughput manner. However, an Y2H chemical screen tends to isolate false
      positive molecules, and therefore a secondary in planta screen is required to
      confirm the genuine bioactivity of putative positive hits. This two-step
      screening approach can substantially save time and manual labor. This chapter
      focuses on the prospects of Y2H-based chemical genomic high-throughput screens
      applied to plant hormone perception complexes. Specifically, the method employed
      to carry out a chemical genomic screen to identify agonist and antagonist
      molecules of the phytohormone jasmonic acid in its conjugated form jasmonic acid
      isoleucine (JA-Ile) is described. An easy in planta confirmation assay is also
      illustrated. However, this methodology can be easily extended to detect novel
      chemical compounds perturbing additional plant hormone receptor complexes.
      Finally, the high-throughput approach described here can also be implemented for
      the identification of molecules interfering with protein-protein interaction of
      plant complexes other than hormone receptors. 

PMID- 24306861
TI  - High-throughput screening of small-molecule libraries for inducers of plant
      defense responses.
AB  - Transgenic Arabidopsis seedlings containing a pathogen-responsive reporter gene
      allow for convenient high-throughput screening of chemical libraries for
      compounds that induce plant defense responses. Candidates identified by such
      screens can be further tested for their ability to protect plants from pathogen
      caused diseases. Using Arabidopsis defense signaling mutants, defined regulatory
      processes that are targeted by a given candidate molecule can be easily narrowed
      down. Here, we provide a detailed high-throughput screening protocol for library
      compounds that activate a pathogen-responsive reporter gene in liquid-grown
      Arabidopsis seedlings. 

PMID- 24306862
TI  - Using a reverse genetics approach to investigate small-molecule activity.
AB  - Chemical genomics is a highly effective approach for understanding complex and
      dynamic biological processes in plants. A chemical activity can be investigated
      by a reverse genetics strategy, for which a huge abundance and diversity of
      Arabidopsis thaliana mutants are readily available for exploitation. Here we
      present an approach to characterize a chemical of interest, as well as examples
      of studies demonstrating an effective combination of chemical genomics with
      reverse genetics strategies, drawn from recent literature on phytohormone
      signalling and auxin transport. 

PMID- 24306863
TI  - Investigating the phytohormone ethylene response pathway by chemical genetics.
AB  - Conventional mutant screening in forward genetics research is indispensible to
      understand the biological operation behind any given phenotype. However, several
      issues, such as functional redundancy and lethality or sterility resulting from
      null mutations, frequently impede the functional characterization of genetic
      mutants. As an alternative approach, chemical screening with natural products or
      synthetic small molecules that act as conditional mutagens allows for identifying
      bioactive compounds as bioprobes to overcome the above-mentioned issues. Ethylene
      is the simplest olefin and is one of the major phytohormones playing crucial
      roles in plant physiology. Most of the current information on how ethylene works
      in plants came primarily from genetic studies of ethylene mutants identified by
      conventional genetic screening two decades ago. However, we lack a complete
      picture of functional interaction among components in the ethylene pathway and
      cross talk of ethylene with other phytohormones. Here, we describe our
      methodology for using chemical genetics to identify small molecules that
      interfere with the ethylene response. We set up a phenotype-based screening
      platform and a reporter gene-based system for verification of the hit compounds
      identified by chemical screening. We have successfully identified small molecules
      affecting the ethylene phenotype in etiolated seedlings and showed that a group
      of structurally similar compounds are novel inhibitors of ACC synthase, a rate
      limiting enzyme in the ethylene biosynthesis pathway. 

PMID- 24306864
TI  - Screening for inhibitors of chloroplast galactolipid synthesis acting in membrano
      and in planta.
AB  - The knowledge of the membrane lipid metabolism in photosynthetic cells is
      expected to benefit from the availability of inhibitors acting at the level of
      specific enzymes like MGD1 (E.C. 2.4.1.46) that catalyzes the synthesis of
      monogalactosyldiacylglycerol (MGDG) in chloroplasts. MGDG is a major lipid of
      photosynthetic membrane, interacting with photosystems. It is the precursor of
      digalactosyldiacylglycerol that serves as a phospholipid surrogate when plants
      are deprived of phosphate, and it is a source of polyunsaturated fatty acids for
      jasmonic acid syntheses. MGD1 is activated by phosphatidic acid and thus a
      coupling point between phospholipid and galactolipid metabolisms. Here we
      describe a method to screen for inhibitors of MGD1 assayed in liposomes. Selected
      compounds can therefore reach the core of the biological membranes in which the
      target sits. We then describe a secondary screen to evaluate the efficiency of
      developed compounds at the whole plant level. Major issues raised by the
      screening of inhibitors acting on membrane proteins are discussed and can be
      useful for similar targets. 

PMID- 24306865
TI  - Forward chemical screening of small RNA pathways.
AB  - RNA silencing is a mechanism of gene expression regulation mediated by short
      noncoding RNAs called small RNAs. Small RNAs can suppress gene expression
      transcriptionally or posttranscriptionally by base pairing to their targets. In
      plants, they are involved in a diverse range of pathways and processes. Forward
      genetic screens have led to the identification of many components in small RNA
      biogenesis and functional pathways. However, it cannot identify essential or
      functionally redundant genes. Forward chemical screens can overcome these
      limitations by targeting multiple redundant proteins within a family and by
      giving the user temporal control of the application of the chemical. Here, we
      describe a method to quickly screen chemicals that perturb small RNA pathways
      using Arabidopsis thaliana reporter lines in a 96-well format. 

PMID- 24306866
TI  - Identification and use of fluorescent dyes for plant cell wall imaging using high
      throughput screening.
AB  - Plant cell walls define cell shape during development and are composed of
      interlaced carbohydrate and protein networks. Fluorescent dyes have long been
      used to label plant cell walls, enabling optical microscopy-based interrogation
      of cell wall structure and composition. However, the specific cell wall
      components to which these dyes bind are often poorly defined. The availability of
      fluorescent compound libraries provides the potential to screen for and identify
      new fluorescent compounds that interact with specific plant cell wall components,
      enabling the study of cell wall architecture in intact, living tissues. Here, we
      describe a technique for screening fluorescent compound libraries for enhanced
      fluorescence upon interaction with plant cell walls, a secondary screening method
      to identify which cell wall components interact with a given dye, and a protocol
      for staining and observing Arabidopsis seedlings using a fluorescent cell wall
      labeling dye. These methods have the potential to be applied to screening for
      differences in cell wall structure and composition among genetically diverse
      plant varieties or species. 

PMID- 24306867
TI  - High-throughput identification of chemical endomembrane cycling disruptors
      utilizing tobacco pollen.
AB  - Endomembrane cycling processes in plants remain mostly intractable through
      classical genetic interrogation. Chemical disruption of these processes provides
      an opportunity to slow or inhibit these processes for study. Tobacco pollen,
      which is dependent upon endomembrane cycling for tube growth, provides a plant
      system that is amenable to high-throughput screening of chemical disruptors. We
      describe here the process that allowed the identification of over 360
      endomembrane cycling disruptors. 

PMID- 24306868
TI  - Plant chemical genomics: gravity sensing and response.
AB  - The gene families that encode the vesicle trafficking machinery in plants are
      highly expanded compared to those from protists and animals. As such, classical
      genetic screens for mutants with lesions in these genes are fraught with issues
      of redundancy and lethality. A chemical genomics approach can, in theory,
      circumvent these issues because inhibitory or stimulatory molecules may be
      applied at any point in development at sublethal concentrations. This chapter
      describes the protocols for a chemical genomics screen designed to identify
      components of the plant cell vesicle trafficking machinery. A two-tiered screen
      was designed where the primary screen assayed for chemicals that modified the
      gravitropic response, a process that in plant cells is intimately tied to vesicle
      trafficking; the secondary screen employed fluorescent marker lines that were
      treated with gravitropic inhibitors or inducers to assay for changes in
      endomembrane system morphology. We thus identified four compounds by which we can
      further explore the relationship between gravitropic signal transduction and
      vesicle trafficking. 

PMID- 24306869
TI  - Screening chemical libraries for compounds that affect protein sorting to the
      yeast vacuole.
AB  - Protein trafficking to the yeast vacuole has been extensively studied using a
      series of deletion mutants. In these genetic screens, mis-targeted vacuolar cargo
      proteins were used as phenotype markers. Here we describe a similar approach
      employing pharmacological effects of diverse chemical compounds to mimic
      molecular phenotypes caused by conventional genetic mutations in protein
      trafficking genes. 

PMID- 24306870
TI  - The use of multidrug approach to uncover new players of the endomembrane system
      trafficking machinery.
AB  - Chemical Biology is a strong tool to perform experimental procedures to study the
      Endomembrane System (ES) in plant biology. In the last few years, several
      bioactive compounds and their effects upon protein trafficking as well as
      organelle distribution, identity, and size in plants and yeast have been
      characterized. Today, several of these chemical tools are widely used to perform
      mutant screens and establish the trafficking pathway of a given cellular
      component. This chapter is a guideline to perform multidrug approaches to study
      the endomembrane system in plant cells. This type of approach is a powerful and
      useful strategy to thoroughly determine the trafficking of a specific protein as
      well as to perform mutant screens based on phenotypes produced by drug
      treatments. On the other hand, a multidrug approach can address the
      characterization of a new bioactive molecule and find its cellular pathway
      target. Overall, this approach can unravel mechanisms and identify new players in
      endomembrane trafficking. 

PMID- 24306871
TI  - Cheminformatic analysis of high-throughput compound screens.
AB  - This article gives an overview of basic computational methods that are commonly
      used for analyzing small molecule screening data in the chemical genomics field.
      First, we introduce cheminformatic concepts for analyzing drug-like small
      molecule structures and their properties. Second, we introduce compound selection
      approaches for assembling screening libraries using compound property and
      diversity analyses. Finally, we discuss methods for interpreting screening hits
      by analyzing compound structures and induced phenotypes using similarity search
      and clustering approaches. These are critical steps for optimizing screening
      hits, and relating structure to bioactivity and phenotype. 

PMID- 24306872
TI  - Endomembrane dissection using chemically induced bioactive clusters.
AB  - Chemical genomics is a novel approach that allows for the rapid functional
      analysis of plant proteins, complexes, pathways, and networks. Systematic screens
      for bioactive small molecules causing specific subcellular phenotypes have been
      successfully performed in mammalian cells, but thus far, are limited in plants.
      This protocol describes a systematic chemical screen of plasma membrane recycling
      markers in plants, using confocal microscopy and the subsequent clustering of
      subcellular phenotypes, to identify chemicals with desired effects. The method
      provides an approach to identify novel chemicals for pathway dissection, making
      chemical genomics more accessible to the scientific community. The matrix of
      novel chemicals described in this protocol can be expanded and analyzed
      continuously as more data is collected, increasing our knowledge of the
      endomembrane system, and accumulating compartment-specific markers and chemical
      probes that perturb specific aspects of endomembrane trafficking. 

PMID- 24306873
TI  - Statistical molecular design: a tool to follow up hits from small-molecule
      screening.
AB  - In high-throughput screening (HTS) a robust assay is used to interrogate a large
      collection of small organic molecules in order to find compounds, hits, with a
      desired biological activity. The hits are then further explored by an iterative
      process where new compounds are designed, purchased, or synthesized, followed by
      an evaluation in one or more assays. Statistical molecular design (SMD) is a
      useful method to select a balanced, varied, and information-rich compound
      collection based on hits from HTS in order to create a foundation for development
      of optimized compounds with improved properties. In this chapter, we describe the
      use of SMD to explore a hit obtained from small-molecule screening. 

PMID- 24306874
TI  - Early stage hit triage for plant chemical genetic screens and target site
      identification.
AB  - The increasing use of plant biological screens of large compound libraries to
      discover informative chemical probes for plant chemical genetics requires
      efficient methods for hit selection and advancement. Downstream target
      identification and validation studies with selected chemistries can also be
      resource-intensive and have a significant failure rate. Several steps and
      considerations for early stage hit triage are outlined to increase the
      probability of success that downstream studies with the chemical probe will be
      robust and productive, especially for target site discovery. Conversely,
      problematic compounds can be shelved or avoided entirely, saving time and
      resources. These steps include assessment of compound availability, purity,
      stability and solubility; determination of the biological dose-response; early
      and iterative evaluation of analogs; avoidance of promiscuous "frequent-hitters";
      consideration of physicochemical parameters affecting compound bioavailability
      and mobility, use of "low-barrier" biological testing systems; and assessing the
      potential for compound metabolism or bioconversion. 

PMID- 24306875
TI  - Screening for gene function using the FOX (full-length cDNA overexpressor gene)
      hunting system.
AB  - Mutant resources are indispensable for the characterization of the functions of
      genes. There are two types of mutants, loss-of-function and gain-of-function
      mutants. Recently, we have developed a novel system in plants that uses a gain-of
      function approach and is named as the FOX (full-length cDNA overexpressor gene)
      hunting system. In this system, Arabidopsis full-length cDNAs (fl-cDNAs) are
      randomly over-expressed under the control of the cauliflower mosaic virus (CaMV)
      35S promoter in Arabidopsis plants. These transgenic plants, or Arabidopsis FOX
      lines, possess ectopically expressed fl-cDNAs in their genome. Chemical genomics
      is a newly emerging field that connects chemical biology with genomes. Since each
      FOX line expresses an excess amount of the protein from the transgene it can be
      resistant or hypersensitive to bioactive chemicals when the protein is the target
      for the chemical. In this protocol, we describe the procedure for identification
      of the fl-cDNAs responsible for the target of the chemical or for the signal
      transduction pathway involving the chemical. 

PMID- 24306876
TI  - Quantification of stable isotope label in metabolites via mass spectrometry.
AB  - Isotope labelling experiments with stable or radioactive isotopes have long been
      an integral part of biological and medical research. Labelling experiments led to
      the discovery of new metabolic pathways and made it possible to calculate the
      fluxes responsible for a metabolic phenotype, i.e., the qualitative and
      quantitative composition of metabolites in a biological system. Prerequisite for
      efficient isotope labelling experiments is a reliable and precise method to
      analyze the redistribution of isotope label in a metabolic network. Here we
      describe the use of the CORRECTOR program, which utilizes matrix calculations to
      correct mass spectral data from stable isotope labelling experiments for the
      distorting effect of naturally occurring stable isotopes (NOIs). CORRECTOR
      facilitates and speeds up the routine quantification of experimentally introduced
      isotope label from multiple mass spectral readouts, which are generated by
      routine metabolite profiling when combined with stable isotope labelling
      experiments. 

PMID- 24306877
TI  - 1H NMR-based metabolomics methods for chemical genomics experiments.
AB  - Metabolomics and chemical genomics studies can each provide unique insights into
      plant biology. Although a variety of analytical techniques can be used for the
      interrogation of plant systems, nuclear magnetic resonance (NMR) provides
      unbiased characterization of abundant metabolites. An example methodology is
      provided for probing the metabolism of Arabidopsis thaliana in a chemical
      genomics experiment including methods for tissue treatment, tissue collection,
      metabolite extraction, and methods to minimize variance in biological and
      technical sample replicates. Additionally, considerations and methods for data
      analysis, including multivariate statistics, univariate statistics, and data
      interpretation are included. The process is illustrated by examining the
      metabolic effects of chemical treatment of Arabidopsis with Sortin 1, also known
      as vacuolar protein sorting inhibitor 1. Sortin 1 was applied to Arabidopsis
      seedlings to examine metabolic effects in a chemical genomics experiment and to
      demonstrate the utility of metabolomics in conjunction with other "omics"
      techniques. 

PMID- 24306878
TI  - Determination of auxin transport parameters on the cellular level.
AB  - The accumulation of radioactively labelled compounds in cells is frequently used
      for the determination of activities of various transport systems located at the
      plasma membrane, including the system for carrier-mediated transport of plant
      hormone auxin. The measurements of auxin transport could be performed on the
      tissue level as well, but for more precise quantitative analysis of activity of
      individual auxin carriers the model of plant cell cultures represents an
      invaluable tool. Here, we describe the method for the determination of the
      activities of auxin influx and efflux carriers in plant cells grown in a
      suspension using radiolabelled synthetic auxins 2,4-dichlorophenoxyacetic acid
      (2,4-D) and naphthalene-1-acetic acid (NAA). By making use of specific inhibitors
      of active auxin influx and efflux, as well as cell lines overexpressing or
      silencing particular auxin carriers, this method allows the determination of
      kinetic parameters of auxin flow across the plasma membrane and the activity of
      those carriers. 

PMID- 24306879
TI  - Analyzing the in vivo status of exogenously applied auxins: a HPLC-based method
      to characterize the intracellularly localized auxin transporters.
AB  - Exogenous application of biologically important molecules for plant growth
      promotion and/or regulation is very common both in plant research and
      horticulture. Plant hormones such as auxins and cytokinins are classes of
      compounds which are often applied exogenously. Nevertheless, plants possess a
      well-established machinery to regulate the active pool of exogenously applied
      compounds by converting them to metabolites and conjugates. Consequently, it is
      often very useful to know the in vivo status of applied compounds to connect them
      with some of the regulatory events in plant developmental processes. The in vivo
      status of applied compounds can be measured by incubating plants with
      radiolabeled compounds, followed by extraction, purification, and HPLC metabolic
      profiling of plant extracts. Recently we have used this method to characterize
      the intracellularly localized PIN protein, PIN5. Here we explain the method in
      detail, with a focus on general application. 

PMID- 24306880
TI  - New treatment options for lung adenocarcinoma--in view of molecular background.
AB  - Lung cancer is the leading cause of cancer related mortality all over the world,
      and a number of developments have indicated future clinical benefit recently. The
      development of molecular pathology methods has become increasingly important in
      the prediction of chemotherapy sensitivity and mutation analysis to identify
      driver mutations as important targets of new therapeutic agents. The most
      significant changes in the treatment of NSCLC revealed in new pathologic
      classification and in the introduction of molecularly targeted therapies, which
      include monoclonal antibodies and small molecule tyrosine kinase inhibitors. The
      side effects of these agents are generally better tolerated than those of
      conventional chemotherapy and show higher efficacy. The most important factor
      follows: histology subtypes, gene mutation status, patients' selection, drug
      toxicities and occurence of drug resistance. In the advanced disease, the hope of
      cure is less than 3%, but improvements in survival have been clearly achieved.
      Some years ago the median lung cancer survival rate was 10-12 months, now in case
      of available specific molecular targets, a significant increase in median
      survival rates to 24-36 months has been achieved. These agents give an
      opportunity to provide a new standard of care. Therefore testing EGFR mutations
      and ALK rearrangements in patients with advanced lung adenocarcinoma should be
      incorporated into routine clinical practice. This review focuses on the rationale
      for targeted agents and new treatment possibilities in case of advanced lung
      adenocarcinoma.

PMID- 24306882
TI  - Stimulation by abscisic acid of RNA synthesis in discs from healthy and tobacco
      mosaic virus-infected tobacco leaves.
AB  - Uptake of abscisic acid from the culture medium by discs of healthy and tobacco
      mosaic virus-infected tobacco leaves was measured. Small (two to five-fold)
      increases in abscisic acid concentration in discs caused increases in rates of
      [(3)H]uridine and [(3)H]adenine incorporation into total nucleic acid, virus RNA
      and host ribosomal RNA. Net accumulation of virus RNA was also enhanced by
      abscisic acid. This evidence for stimulation of RNA synthesis is compared with
      previous reports showing inhibition of RNA synthesis in other tissues. It is
      suggested that the increase in endogenous abscisic acid caused by tobacco mosaic
      virus infection may be at least partly responsible for observed increases in
      rates of RNA synthesis after infection. 

PMID- 24306881
TI  - Hodgkin disease therapy induced second malignancy susceptibility 6q21 functional
      variants in roma and hungarian population samples.
AB  - Patients treated successfully for pediatric Hodgkin's lymphoma are known to
      develop secondary malignancies; care is already taken in treatment to prevent
      this adverse effect. Recent GWAS study identified rs4946728 and rs1040411
      noncoding SNPs located between PRDM1 and ATG1 genes on chromosome 6q21 as risk
      factors for secondary malignancies in patients formerly treated with radiotherapy
      for pediatric Hodgkin disease. We investigated the allele frequencies of these
      two SNPs in biobanked, randomly selected DNA of average, apparently healthy
      Hungarians (n = 277) and in samples of Roma (n = 279) population living Hungary.
      The risk allele frequency for rs4946728 was 79.4 % in Hungarian and 83.5 % in
      Roma samples, while for rs1040411 it was 56.4 % in Hungarian and 55.8 % in Roma
      samples. These values are quite similar in the two populations, and are rather
      high. The values are higher than those frequencies observed in the controls
      (rs4946728: 59.1 % and rs1040411: 39.6 %, p < 0.05), and are in the range of the
      cases (86 % and 68.2 %, respectively) of the above original GWAS study. Our
      findings suggest, that beside the already taken precautions, genetic
      characterization of Hungarian pediatric Hodgkin patients seems to be advantageous
      prior to the treatment of their disease.

PMID- 24306883
TI  - Heavy-meromyosin-decoration of microfilaments from Mougeotia protoplasts.
AB  - The cell wall of the green alga Mougeotia was enzymatically digested by macerase
      and cellulysin. Released protoplasts were spread on poly-L-ornithine, formvar
      carbon-coated grids, and cell fragments were collected for structural
      characterization. Large numbers of 5-7 nm filaments are seen which may be
      decorated with heavy meromyosin (HMM), a digest product of muscle myosin that
      binds specifically to actin, supporting the hypothesis that the phytochrome
      mediated chloroplast movements in these algae are driven by a contractile complex
      of actomyosin. 

PMID- 24306884
TI  - Fine structure, pattern of division, and course of wound phloem in Coleus blumei.
AB  - The wound phloem bridges which have developed six days after interrupting an
      internodal vascular bundle contain wound sieve-elements, companion cells, and
      phloem parenchyma cells. An analysis of the meristematic activity responding to
      the wounding clearly demonstrates that three consecutive divisions are
      prerequisite to the formation of phloem mother-cells. Companion cells are
      obligatory sister cells of wound sieve-elements, connected to the latter by
      specific plasmatic strands and provided with a dense protoplast. Six days after
      wounding most of the wound sieve-elements are still at a nucleate state of
      development, but already have characteristic P-protein bodies and plastids
      containing sieve-element starch. Their cytoplasmic differentiation corresponds to
      the changes recorded during maturation of ordinary sieve elements. Sieve-plate
      pores penetrate through preexisting parenchyma cell walls, only, and develop from
      primary pitfield-plasmodesmata. Wound sieve-elements do not connect to
      preexisting bundle sieve-elements, they open a new tier of young sieve elements
      produced by cambial activity. 

PMID- 24306885
TI  - Analysis of picogram quantities of indole-3-acetic acid by high performance
      liquid chromatography-fluorescence procedures.
AB  - The use of spectrofluorimeter coupled to a reverse phase high performance liquid
      chromatography column permits selective detection of indole-3-acetic acid at the
      low picogram level. The value of the technique is demonstrated by the analysis of
      endogenous IAA in elongating shoots, xylem sap and callus of Douglas-fir. The
      data are also used to illustrate a procedure whereby the accuracy of
      chromatographic analyses can be verified within definable probability limits. 

PMID- 24306886
TI  - The role of the epidermis in auxin-induced and fusicoccin-induced elongation of
      Pisum sativum stem segments.
AB  - The effects of peeling and wounding on the indole-3-acetic acid (IAA) and
      fusicoccin (FC) growth response of etiolated Pisum sativum L. cv. Alaska stem
      tissue were examined. Over a 5 h growth period, peeling was found to virtually
      eliminate the IAA response, but about 30% of the FC response remained. In
      contrast, unpeeled segments wounded with six vertical slits exhibited significant
      responses to both IAA and FC, indicating that peeling does not act by damaging
      the tissue. Microscopy showed that the epidermis was removed intact and that the
      underlying tissue was essentially undamaged. Neither the addition of 2% sucrose
      to the incubation medium nor the use of a range of IAA concentrations down to 10(
      8) M restored IAA-induced growth in peeled segments, suggesting that lack of
      osmotic solutes and supra-optimal uptake of IAA were not important factors over
      this time period. It is concluded that, although the possibility remains that
      peeling merely allows leakage of hydrogen ions into the medium, it seems more
      likely that peeling off the epidermis removes the auxin responsive tissue. 

PMID- 24306887
TI  - Mechanism of effect of aging on membrane transport in leaf strips of Centranthus
      ruber: Possible ethylene involvement in cutting shock.
AB  - Cerulenin has been used to investigate the mechanism by which leaf strips of
      Centranthus ruber (L.) Lam et D.C. increase their capacity for solute uptake
      during a period of incubation in CaSO4 ("aging"). alpha-Aminoisobutyric acid was
      used to assess uptake capability. The leaf strips developed their uptake capacity
      for at least 8-10 h after excision. Cerulenin, if added to the aging medium
      immediately after cutting or at any time during the aging process, almost
      completely halted this development, but did not bring about loss of the uptake
      capacity already achieved. That cerulenin was specifically interfering with fatty
      acid biosynthesis was indicated by the fact that it drastically depressed
      incorporation of labelled acetate into the lipid fraction but did not affect the
      incorporation of labelled alanine. Cycloheximide strongly inhibited the
      development of uptake capacity, but sensitivity to actinomycin D was not evident
      for at least 2 h. The results are consistent with the concept that slicing leads
      to immediate damage to tissue membranes and that "aging" is a process of membrane
      repair, involving renewed synthesis of membrane lipids and membrane proteins.The
      damage to membranes associated with cutting may involve wound ethylene. This is
      indicated by the following findings: Treatment of aged leaf strips with Ethrel (2
      chloroethylphosphonic acid) resulted in drastic loss of their acquired uptake
      capacity. The strips recovered from such Ethrel-induced loss of uptake capacity
      while aging in CaSO4 as they can after cutting. Cerulenin halted recovery of
      uptake capacity after ethrel treatment just as it did after cutting. Treatment of
      leaves before cutting with amino-ethoxyvinylglycine somewhat improved the uptake
      performance of leaf strips immediately after excision. 

PMID- 24306888
TI  - Effects of peeling on the surface structure of the Avena coleoptile: Implications
      for hormone research.
AB  - Coleoptiles of oats (Avena sativa L.) are often peeled in order to observe
      hormone-enhanced acidification of the external medium. It is shown by means of
      the scanning electron microscope that peeling largely removes a single layer of
      cells, the epidermis with its cuticle. Strips of intact and damaged epidermal
      cells remain, but most of the newly exposed surface is composed of cortical
      cells. The cortical face is relatively intact, except that some cells appear
      punctured and some are broken when a vascular bundle is pulled out with the
      epidermis. The surface of the cortex is covered by a thin "film" which is
      partially digested by 2% pectinase. The pectinase pretreatment also inhibits
      indoleacetic-acid- and fusicoccin-enhanced acidification. Thus, although peeling
      could be involved in proton extrusion, physical damage to the coleoptile cells
      per se does not seem to be the major stimulus leading to hormone-enhanced
      acidification. 

PMID- 24306889
TI  - An association between photorespiration and protein catabolism: Studies with
      Chlamydomonas.
AB  - Work demonstrating the operation of a photorespiratory N cycle in Chlamydomonas
      is described. NH3 release by this process is light dependent, sensitive to
      changes in pO2 and pCO2, and abolished by a photosystem II inhibitor. Evidence is
      presented which shows that this NH3 derives its N from protein rather than from
      freshly synthesised glutamate. Protein turnover is shown to provide amino-N at a
      rate sufficient to account for the highest photorespiratory N excretion observed
      suggesting that changes in excretion can be accounted for by increased catabolism
      of normally recirculating amino acids. It is equally possible however that a
      direct link between photorespiration and protein turnover exists, increased NH3
      excretion resulting from enhanced protein turnover. The data suggest that if
      similar mechanisms operate in higher plants, previous estimates of the amount of
      N recycled in photorespiration may have been too high. 

PMID- 24306890
TI  - Appearance and disappearance of proteins in the shoot apical meristem of Sinapis
      alba in transition to flowering.
AB  - Vegetative plants of Sinapis alba L. grown under short days were induced to
      flower by exposure to one long day or continuous long days. Irrespective of the
      number of long days, the first flower primordia were initiated by the shoot
      apical meristem 60 h after the start of the inductive treatment. An indirect
      histoimmunofluorescence technique was used to search in the apical meristem for
      three antigenic proteins which had been previously detected by immunodiffusion
      tests in the whole apical bud (Pierard et al. (1977) Physiol. Plant. 41, 254
      258). One protein called protein A, present in the vegetative meristem, increased
      in concentration during the first 48 h following the start of the inductive
      treatment. It stayed constant up to 96 h and disappeared completely at a later
      time. Two other proteins called B and C, absent in the vegetative meristem,
      appeared in the meristem of induced plants between 30 and 36 h after the start of
      the inductive treatment and progressively accumulated at later times up to 240 h.
      These proteins appeared 8 h before the irreversible commitment of the meristem to
      produce flower primordia (point of no return) was reached and 24 h before start
      of flower production. These observations support an interpretation of floral
      evocation as consisting, at least partially, of an early and qualitative change
      in gene expression. 

PMID- 24306891
TI  - Small RNA species in maize tissue.
AB  - The low molecular weight RNA components of maize have been analyzed after
      labeling callus and leaf tissue with [(3)H]uridine in vitro. Electrophoresis of
      the isolated RNA on acrylamide slab gels reveals, apart from 5S and transfer RNA,
      three major and about five minor RNA species with chain lengths between 140 and
      280 nucleotides. These RNA molecules are labeled as rapidly as 5S, transfer RNA,
      and do not represent degradation products of large ribosomal RNA molecules.
      Furthermore, like 5S and transfer RNA, these small RNA species are stable and
      show no detectable turnover within forty-eight hours. Fractionation of the tissue
      into crude subcellular fractions indicates a preferential association of some of
      the small stable RNA species with the nucleus, while others appear to be located
      in the cytoplasm. The low molecular weight RNA spectrum from the leaf is similar
      to that observed in callus, with the major small RNA species equally present in
      both tissues. 

PMID- 24306892
TI  - Incorporation of [2(14)C]malonyl CoA into fatty acids by a cell-free extract of
      Catharanthus roseus suspension culture cells.
AB  - A cell-free extract containing the enzymes for de-novo synthesis, elongation and
      desaturation of fatty acids was prepared from cultured cells of Catharanthus
      roseus G. Don. (14)C-Fatty acids synthesized by the extract from [2-(14)C]malonyl
      CoA substrate were palmitic (16:0), stearic (18:0) and oleic (18:1). Dialyzed
      extract was active and stable at room temperature and at 4 degrees  C, but was
      inactivated on boiling. There was an absolute requirement for NADPH for
      incorporation of [2-(14)C]malonyl CoA into total fatty acids. Escherichia coli
      acyl carrier protein stimulated total fatty-acid synthesis without affecting the
      relative ratio of individual fatty acids. Total fatty-acid synthesis at a rate of
      45 nmol.mg(-1) protein.h(-1) occurred at a substrate level of 73 MUM malonyl CoA,
      cofactor levels of 500 MUM NADPH, 30 MUg.ml(-1) E. coli ACP, and 1.0 mg.ml(-1)
      extract protein. Total fatty acid synthesis was also sensitive to cerulenin and
      CoA levels. Variations in the relative abundance of individual (14)C-fatty acids
      were regulated by concentrations of [(14)C]malonyl CoA. NADPH and ferredoxin, as
      well as by pH, temperature and length of incubation. Fatty-acid synthetase
      enzymes responsible for [(14)C]palmitic acid were rapidly saturated at a low
      substrate level (0.3 MUM malonyl CoA). Increasing the level of [2-(14)C]malonyl
      CoA permitted further synthesis of [(14)C]stearate and [(14)C]oleate.
      Desaturation of [(14)C]stearate to [(14)C]oleate was stimulated by increasing the
      levels of NADPH and ferredoxin. The desaturase and elongase enzymes were
      sensitive to acidic pH. The desaturase was also unstable at 41 degrees  C,
      although fatty acid synthetase and elongase were unaffected by this temperature. 

PMID- 24306893
TI  - Immunocytochemical localization of reserve protein in the endoplasmic reticulum
      of developing bean (Phaseolus vulgaris) cotyledons.
AB  - The ultrastructure of the storage parenchyma cells of the cotyledons of
      developing bean (Phaseolus vulgaris L.) seeds was examined in ultrathin frozen
      sections of specimens fixed in a mixture of glutaraldehyde, formaldehyde and
      acrolein, infused with 1 M sucrose, and sectioned at-80 degrees  C.
      Ultrastructural preservation was excellent and the various subcellular organelles
      could readily be identified in sections which had been stained with uranyl
      acetate and embedded in Carbowax and methylcellulose. The cells contained large
      protein bodies, numerous long endoplasmic reticulum cisternae, mitochondria,
      dictyosomes, and electron-dense vesicles ranging in size from 0.2 to 1.0 MUm.
      Indirect immunolabelling using rabbit immunoglobulin G against purified phaseolin
      (7S reserve protein), and ferritin-conjugated goat immunoglobulin G against
      rabbit immunoglobulin G was used to localize phaseolin. With a concentration of
      0.1 mg/ml of anti-phaseolin immunoglobin G, heavy labeling with ferritin
      particles was observed ober the protein bodies, the cisternae of the endoplasmic
      reticulum, and the vesicles. The same structures were lightly labeled when the
      concentration of the primary antigen was 0.02 mg/ml. Ferritin particles were also
      found over the Golgi bodies. The absence of ferritin particles from other
      organelles such as mitochondria and from areas of cytoplasm devoid of organelles
      indicated the specificity of the staining, especially at the lower concentration
      of anti-phaseolin immunoglobulin G. 

PMID- 24306894
TI  - The effect of light on the biosynthesis of the light-harvesting chlorophyll a/b
      protein : Evidence for the requirement of chlorophyll a for the stabilization of
      the apoprotein.
AB  - The effect of light on the biosynthesis of the light-harvesting chlorophyll a/b
      protein (LHCP) is investigated in wild-type barley (Hordeum vulgare L.) and in
      the chlorophyll b-less mutant chlorina f2. In dark-grown plants a short red light
      pulse triggers the appearance of mRNA activity for the LHCP. While the
      accumulation of this mRNA is controlled by phytochrome (Apel (1979) Eur. J.
      Biochem. 97, 183-188), the red light treatment is not sufficient to induce the
      appearance of the LHCP within the membrane. Thus, at least one of the subsequent
      steps in the biosynthetic pathway leading to the assembly of the LHCP is
      controlled by light. The red light-induced mRNA is taken up into the polysomes
      during the subsequent dark period and is translated in vitro in a cell-free
      protein synthesizing system. However, an accumulation of the freshly synthesized
      polypeptide within the plant is not observed. The apparent instability of the
      polypeptide might be explained by the deficiency of chlorophyll in the red light
      treated plants. In the chlorophyll b-less barley mutant chlorina f2 an
      accumulation of the freshly synthesized apoprotein of the LHCP can be observed in
      the light. Thus, chlorophyll a formation seems to be a light-dependent step which
      is required for the stabilization of the LHCP. 

PMID- 24306895
TI  - The influence of small direct electric currents on the transport of auxin in
      intact plants.
AB  - When a d.c. potential of 9.0 V was applied to the stem of intact pea seedlings
      (Pisum sativum L. cv. Meteor and cv. Alderman) via 10 mM KCl-soaked filter paper
      electrodes placed ca. 50 mm apart the stem passed a steady current of 15-20 MUA
      (resistance ca. 100 kOmega cm(-1)). The basipetal transport of [1-(14)C]IAA
      applied to the apical bud was completely inhibited over the portion of the stem
      through which current flowed and (14)C-labelled compounds accumulated in the
      vicinity of the upper electrode. The inhibition of transport was independent of
      the polarity of the applied potential. The basipetal transport of IAA in the stem
      above the electrode was not affected.Labelled auxin accumulated at the upper
      electrode both as unchanged IAA and as a compound tentatively identified as indol
      3yl-acetyl aspartic acid (IAAsp). These compounds were only slowly remobilised
      when the current was interrupted. However, the ability of the transport system to
      move freshly-applied IAA was rapidly and fully restored when the potential was
      removed. No injury to the plant was detected after maintaining a current flow for
      up to 72 h. No leakage of (14)C-labelled compounds into the KCl solution bathing
      the electrodes was detected. 

PMID- 24306896
TI  - beta-Carotene synthesis in isolated chromoplasts from Narcissus pseudonarcissus.
AB  - A system has been established from isolated intact chromoplasts of Narcissus
      pseudonarcissus flowers that synthesizes geranylgeraniol, an unknown polyprenoid
      alcohol, phytoene, and beta-carotene from [1-(14)C]isopentenyl pyrophosphate in a
      good yeild. Long chain pyrophosphates are not accumulated. San 6706 inhibits the
      dehydrogenation of phytoene, whereas nicotine does not lead to an accumulation of
      lycopene. Separation and identification of polyprenoid lipids was performed by
      HPLC. The properties and advantages of the chromoplast system are discussed. 

PMID- 24306897
TI  - Changes in 1-aminocyclopropane-1-carboxylic-acid content of cut carnation flowers
      in relation to their senescence.
AB  - The rise in ethylene production accompanying the respiration climacteric and
      senescence of cut carnation flowers (Dianthus caryophyllus L. cv. White Sim) was
      associated with a 30-fold increase in the concentration of 1-aminocyclopropane-1
      carboxylic acid (ACC) in the petals (initial content 0.3 nmol/g fresh weight).
      Pretreatment of the flowers with silver thiosulfate (STS) retarded flower
      senescence and prevented the increase in ACC concentration in the petals. An
      increase in ACC in the remaining flower parts, which appeared to precede the
      increase in the petals, was only partially prevented by the STS pretreatment.
      Addition of aminoxyacetic acid (2 mM) to the solution in which the flowers were
      kept completely inhibited accumulation of ACC in all flower parts. 

PMID- 24306898
TI  - The spectrum of statin therapy in cancer patients: is there a need for further
      investigation?
AB  - Although our understanding of the relationship between cancer and statin use
      continues to improve, it remains a complex association requiring further research
      focusing on both biologic and clinical end points in a wide range of patient
      populations. To date, most of the published results are from observational
      studies detailing the risk of incident cancers or from randomized controlled
      trials with cardiovascular primary end points and cancer only as a secondary end
      point. Although there is certainly great value in the information obtained from
      observational studies, they cannot prove a causal link between statins and
      cancer, and it would then seem appropriate to design and implement clinical
      trials. Such studies should consider three main end products of the mevalonate
      pathway (cholesterol, geranyl pyrophosphate, and farnesyl pyrophosphate) from a
      mechanistic perspective, as well as the potential for cancer cell mediation with
      statin use, in addition to pertinent clinical end points including cancer
      incidence and mortality. 

PMID- 24306899
TI  - An organic luminescent molecule: what will happen when the "butterflies" come
      together?
AB  - Cross dipole stacking based on a novel fluorescent molecule, 9,10-bis (2,2
      diphenylvinyl) anthracene (BDPVA), is presented. The butterfly-like structure of
      BDPVA is the key feature to form the unique aggregation structure and such a
      stacking mode is highly beneficial for fluorescence emission, resulting in high
      performance amplified spontaneous emission and electroluminescence of BDPVA. 

PMID- 24306901
TI  - Components of moribund American elm trees as attractants to elm bark
      beetles,Hylurgopinus rufipes and Scolytus multistriatus.
AB  - Hylurgopinus rufipes male and female beetles were attracted to American elms
      infected with Dutch elm disease, and to American elms killed by injection of
      cacodylic acid.H. rufipes was also attracted to solvent extracts of elm, or to
      Porapak Q-trapped volatiles from elm. The major components of attractive
      fractions of Porapak Q-trapped volatiles were isolated, identified, and tested in
      field bioassays. Several artificially compounded mixtures of sesquiterpenes were
      attractive toH. rufipes, although no bait tested was as attractive as diseased
      tree controls. Laboratory bioassays with H. rufipes were marginally successful.
      In laboratory bioassays, nine of 14 sequiterpenes identified from active
      fractions of Porapak extracts elicited significant response from Scolytus
      multistriatus male and female beetles: delta- and gamma-cadinene, alpha-cubebene,
      gamma-muurolene, and beta-elemene were most active. However, in field tests, none
      of the sesquiterpenes alone or in combination significantly attracted S.
      multistriatus, nor did they significantly enhance the attraction of S.
      multistriatus to female-produced pheromone components (4-methyl-3-heptanol [H]
      and alpha-multistriatin [M]). In other field tests, alpha-cubebene (C)
      significantly enhanced response of S. multistriatus to H plus M, but foliage,
      logs, or chips of healthy elm did not enhance trap catch to HMC.

PMID- 24306900
TI  - The right ventricle explains sex differences in survival in idiopathic pulmonary
      arterial hypertension.
AB  - BACKGROUND: Male sex is an independent predictor of worse survival in pulmonary
      arterial hypertension (PAH). This finding might be explained by more severe
      pulmonary vascular disease, worse right ventricular (RV) function, or different
      response to therapy. The aim of this study was to investigate the underlying
      cause of sex differences in survival in patients treated for PAH. METHODS: This
      was a retrospective cohort study of 101 patients with PAH (82 idiopathic, 15
      heritable, four anorexigen associated) who were diagnosed at VU University
      Medical Centre between February 1999 and January 2011 and underwent right-sided
      heart catheterization and cardiac MRI to assess RV function. Change in pulmonary
      vascular resistance (PVR) was taken as a measure of treatment response in the
      pulmonary vasculature, whereas change in RV ejection fraction (RVEF) was used to
      assess RV response to therapy. RESULTS: PVR and RVEF were comparable between men
      and women at baseline; however, male patients had a worse transplant-free
      survival compared with female patients (P = .002). Although male and female
      patients showed a similar reduction in PVR after 1 year, RVEF improved in female
      patients, whereas it deteriorated in male patients. In a mediator analysis, after
      correcting for confounders, 39.0% of the difference in transplant-free survival
      between men and women was mediated through changes in RVEF after initiating PAH
      medical therapies. CONCLUSIONS: This study suggests that differences in RVEF
      response with initiation of medical therapy in idiopathic PAH explain a
      significant portion of the worse survival seen in men.

PMID- 24306902
TI  - Cross-attraction between two species of Matsucoccus : Extraction, bioassay, and
      isolation of the sex pheromone.
AB  - In laboratory bioassays, males of Matsucoccus resinosae from Pinus resinosa in
      New York and Matsucoccus n. sp. from Pinus thunbergiana in Korea were strongly
      attracted to crude hexane extracts of M. resinosae females, and M. resinosae
      males responded strongly to extracts of Matsucoccus n. sp. females. Males of the
      two species responded similarly to gas chromatographic fractions and subfractions
      of a pentane extract of M. resinosae females. Sex pheromones of these two species
      appear to be the same or very similar.

PMID- 24306903
TI  - Stereoselective synthesis of (Z,E)-3,5-tetradecadienyl acetate: Sex attractant
      for carpenterworm moth,Prionoxystus robiniae (Peck) (Lepidoptera: Cossidae) and
      effect of isomers and monounsaturated acetates on its attractiveness.
AB  - A new efficient stereoselective synthesis for (Z,E)-3,5-tetradecadienyl acetate
      (Z3,E5-14?Ac) a potent male sex attractant for the carpenterworm,Prionoxystus
      robiniae (Peck), was developed. The effects of the other three isomers (Z,Z; E,Z;
      E,E) on the field attractiveness of the Z,E isomer toward male P. robiniae were
      determined. The Z, Z isomer inhibited attraction, the E, E isomer synergized
      attraction, and theE,Z isomer had no effect on attraction. Seven monounsaturated
      14-carbon acetates were evaluated for their effect on the attractiveness of Z3,E5
      14?Ac. (E)-3-Tetradecenyl acetate enhanced attraction and (Z)-9- and (E)-5
      tetradecenyl acetate reduced trap captures. (Z,E)-3,5-Tetradecadien-1-ol also
      reduced the attractiveness of Z3,E5-14?Ac.

PMID- 24306904
TI  - Detoxification function of geophagy and domestication of the potato.
AB  - Detoxification as the adaptive function of geophagy is demonstrated from field
      and historical data associating clay consumption with the domestication of
      potentially toxic potatoes. In vitro analyses showed that the glycoalkaloid,
      tomatine, was effectively adsorbed by four classes of edible clays over a range
      of simulated gastrointestinal conditions. These results, in conjunction with
      reports of geophagy by nonhuman primates, suggest geophagy as a solution to the
      impasse chemical deterrents pose to the process of domestication and to chemical
      constraints on plant exploitation by non-fireusing hominids. The inorganic
      component of the chemical environment deserves increased attention from chemical
      ecologists. 

PMID- 24306905
TI  - Isolation of feeding deterrents against argentine stem weevil from ryegrass
      infected with the endophyte Acremonium loliae.
AB  - Infection of ryegrass (Lolium perenne) by an endophytic fungus (Acremonium
      loliae) confers resistance against the Argentine stem weevil (Listronotus
      bonariensis). Extracts from ryegrass clones, infected and uninfected with A.
      loliae, were compared in a feeding choice bioassay, and several fractions were
      identified which affected stem weevil feeding behavior. One stem weevil feeding
      deterrent, peramine C12H17N5O, has been isolated from infected ryegrass and
      partially characterized as a basic indole derivative. Extracts from culturedA.
      loliae had no effect on stem weevil feeding behavior nor was peramine detected in
      the fungal cultures examined. Peramine and the other active substances are
      hydrophilic in contrast to the lipophilic properties reported for the neurotoxic
      lolitrems also isolated from ryegrass infected with A. loliae and associated with
      causing ryegrass staggers disorder in livestock. It is suggested that ryegrass
      staggers and stem weevil feeding deterrency may arise by different biochemical
      mechanisms.

PMID- 24306906
TI  - Male moth sensitivity to multicomponent pheromones: Critical role of female
      released blend in determining the functional role of components and active space
      of the pheromone.
AB  - In the present study male redbanded leafroller (Argyrotaenia velutinana), cabbage
      looper (Trichoplusia ni), and Oriental fruit moths, (Grapholita molesta), were
      tested in a flight tunnel to (1) the major pheromone component, (2) theZ/E
      pheromone component mixtures for Oriental fruit moth and redbanded leafroller,
      (3) and the female-released blends, over a series of dosages. Experiments were
      designed to test the hypothesis that male response downwind of a female is
      initiated by the major component and that minor components function only to
      elicit behaviors close to the female during close-range approach and courtship.
      The results did not support this hypothesis, but rather showed that males
      initiated upwind flight in significantly higher percentages to the complete
      blends of components, at all dosages, compared to single components or partial
      blends. Addition of minor components also signficantly enhanced male perception
      of the major component at lower dosages, resulting in completed flights to
      dosages of the major component that alone did not elicit any upwind flight. Our
      results support the concept that minor components function to enhance male
      sensitivity to the pheromone, and the specificity of the signal. Our results also
      support the hypothesis that the active space of the pheromone is a function of
      the upper and lower concentration thresholds for the blend of components, and not
      simply for the major component. 

PMID- 24306907
TI  - Contents of dufour glands of workers of three species of Tetramorium
      (Hymenoptera: Formicidae).
AB  - The Dufour glands of worker ants of Tetramorium caespitum, and the
      morphologically similar T. impurum are filled with similar, but species-specific
      mixtures of linear hydrocarbons and three homologous sesquiterpene corhpounds.
      Glands of workers ofT. caespitum contain, on average, 70 ng of oil containing C13
      to C17 linear hydrocarbons with n-pentadecane (64%) and a mixture of pentadecenes
      (14%) as major components.T. impurum glands are smaller and contain an average of
      40 ng of the same mixture but with n-pentadecane (49%) and a sesquiterpenoid
      compound (19%) the major components. Two isomeric pentadecenes, (Z)-6-pentadecene
      and (Z)-7-pentadecene are present in both species.T. semilaeve workers contain on
      average only 30 ng of a simple mixture of hydrocarbons with pentadecane
      contributing more than 90% of the total.

PMID- 24306908
TI  - Identification of a volatile attractant for Diabrotica and Acalymma spp. from
      blossoms of Cucurbita maxima duchesne.
AB  - Fractionation of headspace volatiles from Cucurbita maxima blossoms by high
      performance liquid chromatography resulted in the isolation of a single component
      which was highly active in an electroantennogram bioassay on Diabrotica
      undecimpunctata howardi antennae. This compound was identified as indole by gas
      chromatography-mass spectrometry. Field-trapping bioassays were conducted which
      indicated that indole is a potent attractant of the western corn rootworm,D.
      virgifera virgifera, and the striped cucumber beetle,Acalymma vittatum. The
      southern corn rootworm,D. u. howardi, did not respond, despite its strong EAG
      response. The sex ratio ofD. v. virgifera found in indole-baited traps varied
      seasonally. Males were trapped in abundance in late July and later September,
      1983, while females were more abundant August and early September. The
      effectiveness of indole as aD. v. virgifera attractant also varied seasonally. A
      prolonged period of depressed trap catches occurred in early August 1983, during
      the silking and tasseling period of the corn in the field where trapping was
      carried out.

PMID- 24306909
TI  - Soldier defense secretions of the genus Hospitalitermes in Peninsular Malaysia.
AB  - Soldier defense secretions of the genus Hospitalitermes (Isoptera, Termitidae,
      Nasutitermitinae) were chemically analyzed by GC-MS and were found to contain
      volatile monoterpenes and polyoxygenated diterpenes. Interspecific and
      intraspecific chemical variations for H. umbrinus, H. hospitalis, H.
      flaviventris, and H. bicolor are described. Interspecific variations in
      monoterpene and diterpene structures and compositions were evident. A remarkable
      example of large intraspecific variation from a single species was observed inH.
      umbrinus, indicating that colonies of this species can be separable into two
      chemically distinct groups. The diterpenes found in one of these groups have
      unusually high molecular weights.

PMID- 24306910
TI  - Lespedeza phenolics and Penstemon alkaloids: Effects on digestion efficiencies
      and growth of voles.
AB  - Lespedeza cuneata contains high levels of phenolics and is a common food plant of
      the meadow vole (Microtus pennsylvanicus);Penstemon digitalis contains
      substantial quantities of alkaloids and is a common food plant of meadow voles
      and prairie voles (M. ochrogaster). We investigated the palatability of these
      plants and the effects of their secondary compounds on the digestion efficiencies
      and growth of both species of voles. Voles ate very little of either plant when
      alternative food was present. Phenolics and alkaloids were extracted from the
      plants, incorporated into separate artificial diets, and fed to weanling voles
      for three weeks.Lespedeza phenolics reduced the growth of meadow voles but not
      prairie voles throughout the feeding trial. These compounds disrupted digestion,
      reducing protein digestibility by more than half.Penstemon alkaloids lowered only
      the initial growth rates of prairie voles and had no significant effect on meadow
      voles. Prairie voles tended to increase food consumption rates on both Lespedeza
      and Penstemon diets. This response offset some of the decrease in digested
      protein intake in the first case, and offset the increased metabolic cost of
      processing the diet in the latter case. Our results indicate that although
      Lespedeza phenolics and Penstemon alkaloids do influence consumption and
      digestibility of artificial diets, they do not greatly reduce the performance
      (i.e., growth or survival) of voles when consumed at levels generally observed
      for wild voles. However, these compounds probably do place an upper limit on the
      amount of fresh Lespedeza and Penstemon that can be consumed and contribute to
      the generalist feeding strategy of voles.

PMID- 24306911
TI  - Feeding responses of snowshoe hares (Lepus americanus) to volatile constituents
      of red fox (Vulpes vulpes) urine.
AB  - This study investigated the influence of the volatile constituents of red fox
      (Vulpes vulpes) urine in suppressing feeding by snowshoe hares (Lepus americanus)
      on coniferous tree seedlings. Pen and field bioassays indicated that the odor of
      fox urine and its principal component, 3-methyl-3-butenyl methyl sulfide, had a
      negative effect on feeding behavior of hares. The other sulfur-containing
      compounds, 2-phenylethyl methyl sulfide and 3-methylbutyl methyl sulfide, as well
      as six other constituents, were not effective. Synthetic urine mixtures composed
      of eight and nine volatile constituents, respectively, did not suppress feeding
      in pen bioassays. However, the mixture of eight compounds in a field bioassay did
      result in significantly fewer seedlings being eaten by hares than in the control.
      3-Methyl-3-butenyl methyl sulfide may act as an interspecific chemical signal
      which induces a fear or avoidance response in hares. Additional work is required
      to determine the optimum concentration and release system for 3-methyl-3-butenyl
      methyl sulfide to be used as a mammalian semiochemical in crop protection. 

PMID- 24306912
TI  - Identification of cantharidin in false blister beetles (Coleoptera, Oedemeridae)
      from florida.
AB  - Cantharidin, a potent vesicant and antifeedant, is identified for the first time
      in two oedemerid beetles from the western hemisphere. Amounts of the substance
      per beetle were found to range from 2 to 7 MUg inHeliocis repanda and from 15 to
      35 MUg inOxycopis thoracica. Females had two to three times more cantharidin than
      males of the same species. Cantharidin loads of these beetles are sufficient to
      irritate human skin. 

PMID- 24306913
TI  - Idiosyncratic variation in chemical defenses among individual generalist
      grasshoppers.
AB  - The defensive secretion of the lubber grasshopper,Romalea microptera, shows
      extreme chemical variation among individual adults of the same sex within a
      single wild population. Certain phenolic compounds were absent in some
      individuals and present in others. Concentrations of compounds, when present,
      varied over two to three orders of magnitude. Chemical variation attributable to
      individuals accounted for 60-88% of the total quantitative variation and was
      evenly contributed by all individuals in both sexes. Cluster and regression
      analyses showed no discernible predictable patterns in the defensive secretion
      variation. The specificity of chemical cues used by predators may explain why
      these defenses are so idiosyncratic. 

PMID- 24306914
TI  - Sex pheromone ofAdoxophyes orana: Additional components and variability in ratio
      of (Z)-9- and (Z)-11-tetradecenyl acetate.
AB  - Twelve products related to the sex pheromone main components (Z)-9- and (Z)-11
      tetradecenyl acetate (Z9-14?Ac andZ11-14?Ac, respectively), were identified in
      female pheromone gland extracts of the laboratory-reared summerfruit tortrix
      moth,Adoxophyes orana F.v R. These are the geometric isomers and the alcohols of
      the main components, (Z)-9-dodecenyl acetate, (Z)-11-hexadecenyl acetate, and
      saturated acetates of 12-22 carbons. The ratio ofZ9-14?Ac toZ11-14?Ac in
      individuals varied from 3.5?1 to 11?1 with an average of 6.2; their total added
      up to 462 ng/female with an average of 182 ng for 2- to 7-day-old individuals. No
      qualitative or quantitative differences were observed between laboratory and
      field insects.Z9-14?Ac,Z11-14?Ac and the corresponding alcohols were also found
      in female effluvia. Addition of either of the two alcohols to a blend of the two
      acetates augmented trap catch in the field. The same was true for (Z)-9,(E)-12
      tetradecadienyl acetate which was not detected in gland extracts. 

PMID- 24306915
TI  - Chemical mate recognition and release of male sexual behavior in polybiine
      wasp,Belonogaster petiolata (Degeer) (Hymenoptera: Vespidae).
AB  - The results of bioassays using freshly killed gynes ofBelonogaster petiolata
      (Degeer) and hexane extracts of their tagmata and abdominal glands provide
      evidence for the existence of chemical signals in the venom, thorax, and head of
      gynes that serve as mate recognition cues and releasers of copulatory behavior in
      conspecific males. Attraction of males to the source of the chemicals occurs over
      short distances (a few centimeters). 

PMID- 24306916
TI  - Selective olfactory choices of the honeybee among sunflower aromas: A study by
      combined olfactory conditioning and chemical analysis.
AB  - A bioassay based on an olfactory conditioning method simulating the foraging
      situation in laboratory conditions was coupled with chemical analysis of volatile
      sunflower blends. Behavioural data obtained from for-agers'responses to volatile
      fraction point out that honeybees need to use only a limited fraction acting as a
      "simplified aromatic pattern" of the plant, among hundreds of compounds
      constituting the whole aroma. This active fraction included 27 polar compounds
      among which 14 were identified. Extension of such data to crop pollination and
      plant improvement is discussed. 

PMID- 24306917
TI  - Role of secondary metabolites in feeding associations between a predatory
      nudibranch, two grazing nudibranchs, and a bryozoan.
AB  - The carnivorous nudibranch Roboastra tigris preys preferentially upon two
      nudibranchs,Tambja abdere and T. eliora, that in turn feed upon the bryozoan
      Sessibugula translucens. All four organisms contain tambjamines A-D (I-IV) that
      were shown to be fish feeding inhibitors. When attacked by Roboastra, T. abdere
      secretes a distasteful mucus containing a total of 3 mg of the tambjamines that
      sometimes causes the Roboastra to break off the attack. Under similar
      circumstances T. eliora attempts to swim away; it presumably contains
      insufficient of the tambjamines to deter Roboastra. Roboastra follows the slime
      trail of nudibranchs using contact chemoreception and reverses direction when the
      trail is broken. The slime trail ofT. abdere contains low concentrations of the
      tambjamines. In Y-maze experiments,T. eliora was attracted towards seawater
      containing S. translucens and seawater containing 10(-10) M tambjamines A and B
      (1?1) but was repelled by seawater containing > 10(-8) M tambjamines A and B. At
      higher concentrations the mixture of tambjamines may be recognized as an alarm
      pheromone.

PMID- 24306918
TI  - Regulation of the expression of alpha-amylase gene by sodium butyrate.
AB  - Sodium butyrate exerts a pronounced inhibition on the gibberellic acid-induced
      synthesis and secretion of alpha-amylase by aleurone cells of barley seeds. This
      inhibition, which is reversible and non-competitive with cespect to gibberellic
      acid, is concentration dependent, with virtually total inhibition being
      accomplished between 4 and 5 mM sodium butyrate. The pattern of inhibition of
      alpha-amylase formation correlates well with a decrease in the accumulation of
      its messenger RNA. The addition of butyrate 12 h after the addition of
      gibberellic acid to half-seeds, has no effect on the formation and secretion of
      alpha-amylase. It has been shown in earlier studies that the synthesis of alpha
      amylase mRNAs takes about 12 h for completion. The conclusion that butyrate
      interferes with some step in the transcriptional process is supported by a
      decrease observed in the RNAs that hybridize with a cloned alpha-amylase cDNA.
      The results of in vitro translation confirm the inhibition of the formation of
      several translatable mRNAs. Further, immunological probing detected only trace
      amounts of alpha-amylase proteins in the secretion of butyrate-treated seeds.
      Translation of functional mRNAs, post-translational modifications and the
      secretion alpha-amylase are not affected by sodium butyrate. It is concluded that
      butyrate selectively inhibits the transcription of several genes that are under
      the influence of gibberellic acid. This report is the first one documenting the
      inhibitory effect of sodium butyrate on a hormone-induced synthesis and
      accumulation of mRNAs in a plant system. 

PMID- 24306919
TI  - Recombination between mutant cauliflower mosaic virus DNAs.
AB  - A class of mutants of cauliflower mosaic virus (CaMV) DNA was distinguished based
      on its members' ability to induce symptoms when coinoculated on plants with other
      CaMV DNAs mutant at a different locus. Three mutants, one each in open reading
      frame I, III, and VI had this ability. A second class of mutant DNAs did not
      induce symptoms unless combined with a mutant DNA of the first class. Viral DNA
      extracted from diseased plants was shown by restriction enzyme digestion to have
      lost the mutant alleles. When turnip plants were inoculated with a recombining
      mutant derived from DNA of the Cabbage S isolate and a mutant derived from DNA of
      a different isolate, a heterogeneity in the viral DNA extracted from the diseased
      plants was detected by restriction enzyme analysis. Restriction analysis of
      cloned representatives of this heterogeneous population revealed regions
      consistent with repair of heteroduplexes formed during general recombination
      between duplex DNAs. Some regions consistent with this mechanism or with
      recombination by strandswitching during reverse transcription were found. 

PMID- 24306920
TI  - Transcription and translation of heat shock and normal proteins in seedlings and
      developing seeds of soybean exposed to a gradual temperature increase.
AB  - Heat shock proteins (hsps) are synthesized at higher temperatures in soybean
      seedlings exposed to a gradual temperature increase as compared to a rapid heat
      shock (hs). There are differences in the pattern of synthesis of different hsps
      depending on whether the temperature exposure is rapid or gradual. The synthesis
      of normal temperature proteins also occurs at higher temperatures after a gradual
      increase in temperature than after a rapid hs. The increased protein synthesis
      seen with a gradual temperature increase is because of increased mRNA levels. In
      general the mRNAs for actin and the hsps are found at temperatures 6 to 9 degrees
      C higher after a gradual temperature increase than after a rapid hs. While hsps
      are detected in developing seeds after either type of heat treatment an increase
      in the synthesis of hsps is observed at the higher temperatures after a gradual
      temperature increase compared to a rapid hs to the same temperatures. The only
      proteins synthesized at the highest temperatures (49 degrees C) after a gradual
      temperature increase are the precursors of the storage proteins and the hsps.
      After a gradual increase in temperature the mRNAs for the 11S storage proteins
      are present in relatively large amounts up to 43 degrees C decreasing thereafter
      but were detectable at 52 degrees C; whereas, the hsp mRNA levels were relatively
      constant from 40 to 52 degrees C. 

PMID- 24306921
TI  - A chimaeric hygromycin resistance gene as a selectable marker in plant cells.
AB  - We show here that plant cells are sensitive to the antibiotic hygromycin-B(4). We
      also show that a chimaeric gene consisting of the nopaline synthase (nos) gene
      regulatory elements and the E. coli derived hygromycin phosphotransferase (hpt)
      gene, when transferred to plants' cells, confers resistance to hygromycin B. The
      chimaeric nos-hpt gene enables efficient selection of DNA transfer to plant cells
      when used in conjunction with Ti plasmid-derived binary vectors in cocultivation
      experiments. 

PMID- 24306922
TI  - Circular plasmid DNAs from mitochondria of Sorghum bicolor.
AB  - Agarose gel electrophoresis of mitochondrial DNA (mtDNA) from the IS1112C male
      sterile cytoplasm of Sorghum bicolor (S. bicolor) revealed plasmid-like DNAs
      additional to the linear N1 and N2 molecules. Mitochondrial plasmids were
      separated from the principal mitochondrial genome and used in the construction of
      molecular clones. Clones with EcoRI inserts of 1.7 and 2.3 kb were recovered.
      Hybridization of these clones to Southern blots of unrestricted and EcoRI
      digested IS1112C mitochondrial plasmids indicated the cloned inserts were
      complete or nearly-complete copies of minicircular DNA molecules. These clones
      were used to probe Southern blots of mitochondrial genomes from six cytoplasmic
      male-sterile (CMS) and five male-fertile (MF) lines of S. bicolor, as well as
      Southern blots of IS1112C chloroplast, kafir chloroplast, IS1112C nuclear, and
      kafir nuclear genomes. The 2.3 and 1.7 kb plasmids had a very limited
      distribution among the sorghum entries we examined. We found no evidence for
      integrated copies of these sequences in any of the mitochondrial, chloroplast, or
      nuclear genomes probed in this study. However, the 2.3 kb sorghum minicircle did
      hybridize to the 1.94 kb minicircle from maize mitochondria. Hybridization of the
      1.7 and 2.3 kb clones to IS111L2C mitochondrial RNA reveal a transcript of 1.1 kb
      from the 1.7 kb minicircle and transcripts of 1.9 and 1.4 kb from the 2.3 kb
      molecule. 

PMID- 24306923
TI  - Molecular cloning and nucleotide sequence of cDNA for sporamin, the major soluble
      protein of sweet potato tuberous roots.
AB  - Sporamin accounts for more than 80% of the total soluble proteins of tuberous
      roots of sweet potato, but very little, if any, in other tissues of the same
      plant. In vitro translation of RNA fractions from the tuberous roots in wheat
      germ extract and subsequent immunoprecipitation with the antibody to sporamin
      indicated that this protein is synthesized by membrane-bound polysomes as a
      precursor 4 000 daltons larger than the mature protein. A cDNA expression library
      was constructed from the total poly(A)(+) RNA from the tuberous roots by a vector
      primer method, and an essentially full-length cDNA clone for the sporamin mRNA
      was selected by direct immunological screening of the colonies. Northern blot
      analysis showed that sporamin mRNA is approximately 950 nucleotides in length and
      is specifically present in tuberous roots and very little, if any, in leaves,
      petioles and non-tuberous roots. Nucleotide sequence of the cDNA predicts a 37
      amino acid extension in the precursor at the amino-terminus of the mature
      protein. 

PMID- 24306924
TI  - Different organization of nif genes in nonheterocystous and heterocystous
      cyanobacteria.
AB  - Labeled probes carrying the Anabaena PCC 7120 nitrogenase (nifK and nifD) and
      nitrogenase reductase (nifH) genes were hybridized to Southern blots of DNA from
      diverse N2-fixing cyanobacteria in order to test a previous observation of
      different nif gene organization in nonheterocystous and heterocystous strains.
      The nif probes showed no significant hybridization to DNA from a unicellular
      cyanobacterium incapable of N2 fixation. All nonheterocystous cyanobacteria
      examined (unicellular and filamentous) had a contiguous nifKDH gene cluster
      whereas all of the heterocystous strains showed separation of nifK from
      contiguous nifDH genes. These findings suggest that nonheterocystous and
      heterocystous cyanobacteria have characteristic and fundamentally different nif
      gene arrangements. The noncontiguous nif gene pattern, as shown with two Het(-)
      mutants, is independent of phenotypic expression of heterocyst differentiation
      and aerobic N2-fixation. Thus nif arrangement could be a useful taxonomic marker
      to distinguish between phenotypically Het(-) heterocystous cyanobacteria and
      phylogenetically unrelated nonheterocystous strains. 

PMID- 24306925
TI  - Transcriptome profiling of brain edemas caused by influenza infection and
      lipopolysaccharide treatment.
AB  - Influenza A virus-associated encephalopathy triggered by influenza virus
      infection often occurs in children aged five and younger in Japan. However, the
      mechanisms behind Influenza A virus-associated encephalopathy are not yet well
      understood. This study developed an Influenza A virus-associated encephalopathy
      like model using mice infected with Influenza A virus and given
      lipopolysaccharide treatment. The results showed that the mice used in the model
      suffered from brain edemas nearly three times more severe, as well as having
      higher cytokine levels in sera compared to those of the control groups. Using
      gene expression profiling, cytokine-related genes were found not to be up
      regulated in the brain in situ, while protein coding genes, which are known to be
      involved in blood-brain barrier disruption, were up-regulated. Categorizing the
      functional groups using gene ontology revealed the terms "ion channels," "calcium
      oscillation," and "membrane transporter activities." The blood-brain barrier
      disruption found in this Influenza A virus-associated encephalopathy model can
      therefore be assumed to be due to a cellular electrolyte imbalance of the
      neuronal tissue, in addition to a cytokine storm.

PMID- 24306926
TI  - Measuring social inclusion--a key outcome in global mental health.
AB  - BACKGROUND: Social inclusion is increasingly recognized as a key outcome for
      evaluating global mental health programmes and interventions. Whereas social
      inclusion as an outcome is not a new concept in the field of mental health, its
      measurement has been hampered by varying definitions, concepts and instruments.
      To move the field forward, this paper reviews the currently available instruments
      which measure social inclusion and are reported in the literature, realizing that
      no single measure will be appropriate for all studies or contexts. METHODS: A
      systematic literature search of English language peer-reviewed articles published
      through February 2013 was undertaken to identify scales specifically developed to
      measure social inclusion or social/community integration among populations with
      mental disorders. RESULTS: Five instruments were identified through the search
      criteria. The scales are discussed in terms of their theoretical underpinnings,
      domains and/or key items and their potential for use in global settings. Whereas
      numerous reviewed abstracts discussed mental health and social inclusion or
      social integration, very few were concerned with direct measurement of the
      construct. All identified scales were developed in high-income countries with
      limited attention paid to how the scale could be adapted for cross-cultural use.
      CONCLUSIONS: Social inclusion is increasingly highlighted as a key outcome for
      global mental health policies and programmes, yet its measurement is
      underdeveloped. There is need for a global cross-cultural measure that has been
      developed and tested in diverse settings. However, until that need is met, some
      of the scales presented here may be amenable to adaptation.

PMID- 24306927
TI  - Etiology of familial breast cancer with undetected BRCA1 and BRCA2 mutations:
      clinical implications.
AB  - BACKGROUND: Familial breast cancer accounts for 20-30 % of all breast cancer
      cases. Mutations in the BRCA1 and BRCA2 genes account for the majority of high
      risk families with both early onset breast cancer and ovarian cancer. Most of the
      families with less than six breast cancer cases and no ovarian cancer do not
      carry BRCA1 or BRCA2 mutations that can be detected using routine sequencing
      protocols. Here, we aimed to review the etiology of familial breast cancer in
      cases without BRCA1 and BRCA2 mutations. RESULTS: After excluding BRCA1 and BRCA2
      mutations, factors proposed to contribute to familial breast cancer include:
      chance clustering of apparently sporadic cases, shared lifestyle, monogenic
      inheritance, i.e., dominant gene mutations associated with a high risk (TP53,
      PTEN, STK11), dominant gene mutations associated with a relatively low risk (ATM,
      BRIP1, RLB2), recessive gene mutations associated with horizontal inheritance
      patterns (sister-sister), and polygenic inheritance where susceptibility to
      familial breast cancer is thought to be conferred by a large number of low risk
      alleles. CONCLUSIONS: Current evidence suggests that in the majority of cases
      with BRCA1 and BRCA2 negative familial breast cancer the etiology is due to
      interactions of intermediate or low risk alleles with environmental and lifestyle
      factors. Thus, a careful selection of patients submitted to genetic testing is
      needed. Clearly, further research is required to fully elucidate the etiology of
      non-BRCA familial breast cancer.

PMID- 24306928
TI  - A combination of paclitaxel and siRNA-mediated silencing of Stathmin inhibits
      growth and promotes apoptosis of nasopharyngeal carcinoma cells.
AB  - BACKGROUND: Stathmin, a microtubule associated protein (MAP), is an important
      molecular target for cancer therapy. Paclitaxel is one of the primary antitumor
      drugs targeting microtubules (MTs). We hypothesized that decreasing the
      expression level of Stathmin might improve the effectiveness of paclitaxel in the
      treatment of nasopharyngeal carcinoma (NPC). METHODS: NPC cell lines, CNE1-LMP1
      and HNE2, and a CNE1-LMP1 tumor xenograft mouse model were used to test both in
      vitro and in vivo our siRNA-based Stathmin silencing strategy. The effects of
      Stathmin silencing on cell proliferation, apoptosis, and viability were
      investigated using MTT, AO/EB staining, TUNEL, caspase protein detection, and FCM
      assays. Cell migration and invasion were assayed using a Transwell assay. The
      combined effects of Stathmin silencing and paclitaxel were investigated using
      MTT, FCM, Western blot and indirect immunofluorescence assays. The effect of
      paclitaxel on Stathmin expression in NPC cells and, in addition, A375, MGC and
      HeLa cells was determined by RT-PCR and Western blotting. RESULTS: We found that
      siRNA-mediated silencing of Stathmin suppresses proliferation, induces apoptosis
      through the mitochondrial pathway, and causes G2/M-phase cell cycle arrest in the
      NPC cell lines CNE1-LMP1 and HNE2. Also, the migration and invasion of the
      respective NPC cells were found to be inhibited. In addition, we show that a
      combination of Stathmin silencing and paclitaxel is more effective than either
      agent alone in inhibiting proliferation and inducing apoptosis, cell cycle
      arrest, and MT polymerization. Furthermore, we found that Stathmin expression in
      the tumor cells is down-regulated by paclitaxel treatment. CONCLUSION: siRNA
      mediated silencing of Stathmin suppresses the proliferation, invasion and
      metastasis, and induces the apoptosis of NPC cells. Paclitaxel reduces the
      expression of Stathmin, and combining Stathmin silencing with paclitaxel
      treatment enhances MT polymerization. This combined strategy may provide a new
      approach for clinical NPC treatment.

PMID- 24306929
TI  - Founder niche constrains evolutionary adaptive radiation.
AB  - Adaptive radiation of a lineage into a range of organisms with different niches
      underpins the evolution of life's diversity. Although the role of the environment
      in shaping adaptive radiation is well established, theory predicts that the
      evolvability and niche of the founding ancestor are also of importance. Direct
      demonstration of a causal link requires resolving the independent effects of
      these additional factors. Here, we accomplish this using experimental bacterial
      populations and demonstrate how the dynamics of adaptive radiation are
      constrained by the niche of the founder. We manipulated the propensity of the
      founder to undergo adaptive radiation and resolved the underlying causal changes
      in both its evolvability and niche. Evolvability did not change, but the
      propensity for adaptive radiation was altered by changes in the position and
      breadth of the niche of the founder. These observations provide direct empirical
      evidence for a link between the niche of organisms and their propensity for
      adaptive radiation. This general mechanism may have rendered the evolutionary
      dynamics of extant adaptive radiations dependent on chance events that determined
      their founding ancestors. 

PMID- 24306931
TI  - Three-dimensional architecture of actin filaments in Listeria monocytogenes comet
      tails.
AB  - The intracellular bacterial pathogen Listeria monocytogenes is capable of
      remodelling the actin cytoskeleton of its host cells such that "comet tails" are
      assembled powering its movement within cells and enabling cell-to-cell spread. We
      used cryo-electron tomography to visualize the 3D structure of the comet tails in
      situ at the level of individual filaments. We have performed a quantitative
      analysis of their supramolecular architecture revealing the existence of bundles
      of nearly parallel hexagonally packed filaments with spacings of 12-13 nm.
      Similar configurations were observed in stress fibers and filopodia, suggesting
      that nanoscopic bundles are a generic feature of actin filament assemblies
      involved in motility; presumably, they provide the necessary stiffness. We
      propose a mechanism for the initiation of comet tail assembly and two scenarios
      that occur either independently or in concert for the ensuing actin-based
      motility, both emphasizing the role of filament bundling. 

PMID- 24306932
TI  - Avalanches mediate crystallization in a hard-sphere glass.
AB  - By molecular-dynamics simulations, we have studied the devitrification (or
      crystallization) of aged hard-sphere glasses. First, we find that the dynamics of
      the particles are intermittent: Quiescent periods, when the particles simply
      "rattle" in their nearest-neighbor cages, are interrupted by abrupt "avalanches,"
      where a subset of particles undergo large rearrangements. Second, we find that
      crystallization is associated with these avalanches but that the connection is
      not straightforward. The amount of crystal in the system increases during an
      avalanche, but most of the particles that become crystalline are different from
      those involved in the avalanche. Third, the occurrence of the avalanches is a
      largely stochastic process. Randomizing the velocities of the particles at any
      time during the simulation leads to a different subsequent series of avalanches.
      The spatial distribution of avalanching particles appears random, although
      correlations are found among avalanche initiation events. By contrast, we find
      that crystallization tends to take place in regions that already show incipient
      local order. 

PMID- 24306933
TI  - Desiccation tolerance in diapausing spider mites Tetranychus urticae and T.
      kanzawai (Acari: Tetranychidae).
AB  - We investigated the effects of changes in vapor pressure deficit (VPD) on the
      survival of diapausing (winter form) and non-diapausing (summer form) spider
      mites Tetranychus urticae Koch and Tetranychus kanzawai Kishida (Acari:
      Tetranychidae). Adult females of both species were kept without food at VPDs of
      0.0, 0.4, 0.7, 1.5, 1.9, or 2.7 kPa for 3, 6, 9, 12, or 15 days at 25  degrees C.
      Diapausing females of both species kept at a VPD of >=0.4 kPa for >=6 days
      clearly tolerated desiccation. Under water-saturated conditions (VPD = 0.0 kPa),
      in which no desiccation occurred, diapausing females showed high starvation
      tolerance: 90 % survived for up to 15 days. No interspecific differences in
      tolerance to desiccation or starvation were observed under most conditions. These
      results indicate that diapause functions increase tolerance to desiccation and
      starvation. Such multiple tolerances to harsh environments might support winter
      survival in spider mites.

PMID- 24306935
TI  - Some mortal paradoxes.

PMID- 24306934
TI  - Assessing physical activity in older adults: required days of trunk accelerometer
      measurements for reliable estimation.
AB  - We investigated the reliability of physical activity monitoring based on trunk
      accelerometry in older adults and assessed the number of measured days required
      to reliably assess physical activity. Seventy-nine older adults (mean age 79.1 +/
      7.9) wore an accelerometer at the lower back during two nonconsecutive weeks.
      The duration of locomotion, lying, sitting, standing and shuffling, movement
      intensity, the number of locomotion bouts and transitions to standing, and the
      median and maximum duration of locomotion were determined per day. Using data of
      week 2 as reference, intraclass correlations and smallest detectable differences
      were calculated over an increasing number of consecutive days from week 1.
      Reliability was good to excellent when whole weeks were assessed. Our results
      indicate that a minimum of two days of observation are required to obtain an ICC
      >= 0.7 for most activities, except for lying and median duration of locomotion
      bouts, which required up to five days. 

PMID- 24306936
TI  - The practice of pastoral care: Revisiting the generalist.
AB  - In a day of reliance on specialists, how can generalist practitioners like clergy
      be confident of the value of their contributions? The theoretical validity and
      practical implications of such religious resources as meaning, mystery,
      providence, values, grace, and community are discussed. Although various
      psychological schools of thought have also confirmed the importance of these
      dynamics, the clergy can validate them from within the discipline of religion
      itself. Thus, ministers as general practitioners in the community can work with
      self-confidence in cooperation with other mental health workers. 

PMID- 24306937
TI  - Psychotherapists and the clergy: Fifty years later.
AB  - Jung's two powerful articles on psychotherapy and the clergy, written in 1928 and
      1932. are looked at from the vantage point of fifty years later and the author's
      experience in conducting analysis with many people from both vocations. He notes
      that relatively few people achieve the kind of integration of the ego that Jung
      writes about-an essentially religious experience-wherein the center of their
      existence now gravitates about the Self. Yet Jung's work and views have had a
      profound effect on spiritually inclined people of all ages. The predictions of
      Jung's articles, regarding therapy, the dissemination of pyschology to the
      masses, and other issues are examined. 

PMID- 24306938
TI  - Neurology, psychology, and extraordinary religious experiences.
AB  - Temporal lobe epilepsy and certain personality disorders often result in
      experiences described as "religious." TLE research suggests a possible
      neurological basis for such experiences. Immediately the question arises about
      the authenticity of these experiences as religious. An experience is authentic if
      it furthers the authentic growth of the subject, regardless of what triggered it.
      So pathology may occasion authentic religious experiences, even as history
      exemplifies. For practical purposes, the further question about God in religious
      experience is secondary. The exception, miraculous occurrences, should not be
      granted without sufficient reason. This approach dissolves all conflict between
      science and faith. 

PMID- 24306939
TI  - Glossolalia and the psychology of the self and narcissism.
AB  - A survey of the religious and psychological literature on glossolalia ("speaking
      in tongues") reviews the various ways that have been used to try to understand
      this fascinating practice. At the present time an impasse has been reached:
      glossolalists can no longer be viewed as suffering from psychopathological
      disorders or from sociological deprivation. Insights derived from the psychology
      of the self and narcissism, as presented in the works of Heinz Kohut and D.W.
      Winnicott, are used to suggest new approaches to understand glossolalia. 

PMID- 24306940
TI  - Touch and technology: Two paradigms of patient care.
AB  - Technology violates human dignity only to the extent that its use reduces persons
      to the moral status of objects. The prevalence of technology in health care is an
      extension of the scientific paradigm, in which the body is reduced to an object
      void of subjectivity. The empathie paradigm, in contrast, is based upon the moral
      primacy of subjectivity. Empathic touch-as distinct from instrumental and
      philanthropic touch-establishes a clinical relation of intersubjectivity,
      affirming in patients the dignity and worth that morally distinguish persons from
      objects. 

PMID- 24306941
TI  - "Soul-making" in a schizophrenic saint.
AB  - "Soul-making" (cf. Jung and Hillman) is the process of integrating spiritual and
      bodily imagery into an intimated wholeness transcending conscious comprehension.
      Pierre Janet's case of the psychotic mystic, Madeleine, reveals that the patient
      had been "making" her own-soul even though his theory had no provision for soul.
      Janet's soul-stripping theory is contrasted with a soul-making approach,
      primarily in their respective interpretations of Madeleine's altered states of
      consciousness. Religious ecstasy is a "stretching" of soul, an expansion into the
      realm of "spirit," which requires a subsequent descent into and reconciliation
      with tradition, society, outer world, and body. 

PMID- 24306942
TI  - Human stem cell models of neurodegeneration: a novel approach to study mechanisms
      of disease development.
AB  - The number of patients with neurodegenerative diseases is increasing
      significantly worldwide. Thus, intense research is being pursued to uncover
      mechanisms of disease development in an effort to identify molecular targets for
      therapeutic intervention. Analysis of postmortem tissue from patients has yielded
      important histological and biochemical markers of disease progression. However,
      this approach is inherently limited because it is not possible to study patient
      neurons prior to degeneration. As such, transgenic and knockout models of
      neurodegenerative diseases are commonly employed. While these animal models have
      yielded important insights into some molecular mechanisms of disease development,
      they do not provide the opportunity to study mechanisms of neurodegeneration in
      human neurons at risk and thus, it is often difficult or even impossible to
      replicate human pathogenesis with this approach. The generation of patient
      specific induced pluripotent stem (iPS) cells offers a unique opportunity to
      overcome these obstacles. By expanding and differentiating iPS cells, it is
      possible to generate large numbers of functional neurons in vitro, which can then
      be used to study the disease of the donating patient. Here, we provide an
      overview of human stem cell models of neurodegeneration using iPS cells from
      patients with Alzheimer's disease, Parkinson's disease, amyotrophic lateral
      sclerosis, frontotemporal dementia, Huntington's disease, spinal muscular atrophy
      and other neurodegenerative diseases. In addition, we describe how further
      refinements of reprogramming technology resulted in the generation of patient
      specific induced neurons, which have also been used to model neurodegenerative
      changes in vitro. 

PMID- 24306943
TI  - High-quality conforming hexahedral meshes of patient-specific abdominal aortic
      aneurysms including their intraluminal thrombi.
AB  - In order to perform finite element (FE) analyses of patient-specific abdominal
      aortic aneurysms, geometries derived from medical images must be meshed with
      suitable elements. We propose a semi-automatic method for generating conforming
      hexahedral meshes directly from contours segmented from medical images. Magnetic
      resonance images are generated using a protocol developed to give the abdominal
      aorta high contrast against the surrounding soft tissue. These data allow us to
      distinguish between the different structures of interest. We build novel
      quadrilateral meshes for each surface of the sectioned geometry and generate
      conforming hexahedral meshes by combining the quadrilateral meshes. The three
      layered morphology of both the arterial wall and thrombus is incorporated using
      parameters determined from experiments. We demonstrate the quality of our patient
      specific meshes using the element Scaled Jacobian. The method efficiently
      generates high-quality elements suitable for FE analysis, even in the bifurcation
      region of the aorta into the iliac arteries. For example, hexahedral meshes of up
      to 125,000 elements are generated in less than 130 s, with 94.8 % of elements
      well suited for FE analysis. We provide novel input for simulations by
      independently meshing both the arterial wall and intraluminal thrombus of the
      aneurysm, and their respective layered morphologies. 

PMID- 24306944
TI  - Preoperative assessment of the aortic arch in children younger than 1 year with
      congenital heart disease: utility of low-dose high-pitch dual-source computed
      tomography. A single-centre, retrospective analysis of 62 cases.
AB  - OBJECTIVES: To evaluate the feasibility, image quality and impact of 3D imaging
      in low-dose high-pitch dual-source computed tomography (DSCT) to assess arbitrary
      anatomical malformations of the aortic arch in children <1 year of age with
      congenital heart disease (CHD). METHODS: Between January 2010 and May 2013, DSCT
      was performed to assess the aortic arch anatomy in a total of 62 consecutive
      patients with CHD (aged 0-348 days). DSCT was used whenever conventional
      echocardiography was not sufficient to display the complex anatomy entirely.
      Image data acquisition was realized within a single cardiac cycle using
      prospective ECG triggering. 3D reconstruction for surgical planning was
      performed. Image quality was assessed retrospectively, using a 4-point scale from
      '1 = no artefacts' to '4 = uninterpretable'. The accuracy and impact of the 3D
      reconstructions was compared with intraoperative findings using a 5-point scale
      (from '1 = essential' to '5 = misleading'). Administered radiation exposure was
      evaluated. RESULTS: Imaging was successful in all patients, image quality was
      rated 1.34 on the 4-point scale and the impact of the 3D reconstructions for
      surgical planning was 2.05 on the 5-point scale. Mean dose-length product was 6.8
      +/- 2.6 mGy cm, and the effective dose was 0.45 +/- 0.13 mSv (0.21-0.74).
      CONCLUSIONS: DSCT is a fast and appropriate imaging modality in the preoperative
      assessment of the aortic arch for surgical planning in CHD.

PMID- 24306945
TI  - Periaortic cutaneous fistula 10 years after type A aortic dissection.

PMID- 24306946
TI  - Re: Is valve choice a significant determinant of paravalvular leak post
      transcatheter aortic valve implantation? A systematic review and meta-analysis.

PMID- 24306947
TI  - Late thrombosis of a kinked ascending aortic graft.

PMID- 24306948
TI  - Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in
      a porcine heterotopic valve model.
AB  - OBJECTIVES: Warfarin is used to reduce the risk of stroke and thromboembolic
      complications in patients with mechanical heart valves. Yet, despite frequent
      blood testing, its poor pharmacokinetic and pharmacodynamic profiles often result
      in variable therapeutic levels. Rivaroxaban is a direct competitive factor Xa
      inhibitor that is taken orally. It inhibits the active site of factor Xa without
      the need for the cofactor antithrombin, and thus, its mechanism of action is
      differentiated from that of the fractionated heparins and indirect factor Xa
      inhibitors. No in vivo data exist regarding the effectiveness of rivaroxaban in
      preventing thromboembolic complications of mechanical heart valves. We tested the
      hypothesis that rivaroxaban is as effective as enoxaparin for thromboprophylaxis
      of mechanical valves that use a previously described heterotopic aortic valve
      porcine model. METHODS: A modified bileaflet mechanical valved conduit that
      bypassed the native, ligated descending thoracic aorta was implanted into 30
      swine. Postoperatively, the animals were randomly assigned to groups receiving no
      anticoagulation (n = 10), enoxaparin at 2 mg/kg subcutaneously twice daily (n =
      10) or rivaroxaban at 2 mg/kg orally twice daily (n = 10). The amount of valve
      thrombus was measured on post-implantation day 30 as the primary end point.
      Quantitative evaluation of radiolabelled platelet deposition on the valve
      prostheses was done and embolic and haemorrhagic events were measured as
      secondary end points. RESULTS: Animals with no anticoagulation had a thrombus
      mean of 759.9 mg compared with 716.8 mg with enoxaparin treatment and 209.6 mg
      with rivaroxaban treatment (P = 0.05 for enoxaparin vs rivaroxaban). Similarly,
      the mean number of platelets deposited on the valve prosthesis was lower in the
      rivaroxaban group (6.13 * 10(9)) than in the enoxaparin group (3.03 * 10(10)) (P
      = 0.03). CONCLUSIONS: In this study, rivaroxaban was more effective than
      enoxaparin for short-term thromboprophylaxis of mechanical valve prosthetics in
      the heterotopic aortic position. It reduced valve thrombus and platelet
      deposition on day 30 following implantation without increased adverse events.
      Future studies would provide additional support for clinical trials evaluating
      rivaroxaban as an alternative to warfarin for appropriately selected patients
      with prosthetic aortic valves.

PMID- 24306949
TI  - Adolescence, stress, and psychological well-being.
AB  - The present study analyzes the mental-health consequences of stress in a sample
      of 1,038 adolescents (526 females and 512 males) from a Canadian prairie city.
      The study examined the relationship between perceived stress in family, school,
      and peer-group situations and four measures of psychological well-being, i.e.,
      anxiety, depression, social dysfunction, and anergia. The moderator effects of
      locus of control orientation (mastery) on stress-outcome relationships were also
      examined, as were the sex differences in health and the perception of stress. All
      three sources of stress were found to be related to the four measures of mental
      health, with family stress having the strongest negative health impact. The
      health-protective role of locus of control was limited for the large part to the
      stresses emanating from school and peer groups. Substantial sex differences were
      found in the perception of family- and peer-related stresses as well as in levels
      of psychological distress. A tentative explanation of these differences was
      examined with reference to prevailing structural conditions and differences in
      locus of control orientation, with female adolescents showing greater
      externality. Implications of the results are drawn for the long-standing debate
      on the relative impact of stress and its sources on adolescents' psychosocial
      development and for a current controversy in adolescent theory between proponents
      of "classical" and proponents of "empirical" conceptions of adolescence. 

PMID- 24306950
TI  - Correlates of depressive symptoms in adolescents.
AB  - The relationship between a number of social and cognitive variables and
      depressive symptomatology was evaluated in a sample of public middle-school and
      high-school students. The variables measured included stressful life events,
      locus of control, causal attributions, and means-ends problem-solving abilities.
      Higher levels of depression were found to be associated with a more external
      locus of control and a tendency to attribute outcomes to causes which are
      internal, stable, and global. Parental divorce and socioeconomic status were also
      found to be associated with higher levels of depression. No relationship was
      found to exist between either amount of life stress or problem-solving ability
      and depression. The implications of these results for delineating the underlying
      dimensions of depression in adolescents are discussed. 

PMID- 24306951
TI  - The influences of chronic illness and ego development on self-esteem in diabetic
      and psychiatric adolescent patients.
AB  - Self-esteem as measured by the Coopersmith Self-Esteem Inventory [Coopersmith, S.
      (1967),The Antecedents of Self-Esteem, Freeman, San Francisco] and ego
      development as measured by the Washington University Sentence Completion Test
      [Loevinger, J., and Wessler, R. (1970),Measuring Ego Development, Vol. I, Jossey
      Bass, San Francisco] were evaluated in three groups of early adolescents:
      diabetic patients, nonpsychotic psychiatric patients, and a nonpatient group of
      high-school students. We found that low levels of ego development were associated
      with low levels of global and domain-specific self-esteem in all three subject
      groups. Levels of self-esteem among diabetic patients were not significantly
      different from those of nonpatients. While psychiatric patients had significantly
      lower self-esteem levels than the other groups, this difference was accounted for
      by preconformists, i.e., those at the lowest stages of ego development.
      Psychiatric patients reaching higher ego levels showed self-esteem levels
      indistinguishable from those of the diabetics and nonpatients. 

PMID- 24306952
TI  - Familial correlates of identity formation in late adolescence: A study of the
      predictive utility of connectedness and individuality in family relations.
AB  - Past investigations have documented that late adolescence is associated with
      developmental changes in identity formation resulting in individual differences
      in identity statuses. Particular attention has been given to the identification
      and study of diffusion, foreclosure, moratorium, and identity achievement
      statuses. Drawing from the recent theoretical speculations by Cooper and
      Grotevant, an investigation was completed to assess the predictive utility of
      measures of family connectedness and individuality in differentiating among the
      four identity statuses. Data were obtained from male and female late adolescents
      and their mothers and fathers on perceptions of independence (individuality),
      communication, and emotional affection (connectedness). Differences among
      adolescents grouped into the four identity formation statuses were assessed using
      analysis of variance techniques comparing gender and identity status on measures
      of connectedness and individuality within a parent-adolescent relationship.
      Evidence consistent with the notion that a combination of emotional attachment to
      parents and the encouragement of independence striving by parents is associated
      with healthy identity development emerges from our data. 

PMID- 24306953
TI  - Moral judgment, personality, and attitude to authority in early and late
      adolescence.
AB  - The purpose of this study was to examine the personological features of moral
      judgment and to determine the extent to which principled moral reasoning is
      politically biased. We also attempted to determine the relation between moral
      judgment and attitude to authority and the developmental patterning of attitude
      to authority from early to late adolescence. Attitude to authority was assessed
      in terms of specific sources of authority (mother, father, police, government)
      and by the Attitude to Authority Scale, which assesses attitudes along the
      liberal-conservative political continuum. The conservative personality syndrome
      was assessed by the Conservatism Scale, while moral judgment was assessed by the
      Defining Issues Test. The results indicated that moral reasoning is unrelated to
      attitudes to specific sources of authority and negatively related to political
      conservatism and to conservative personality features. Attitudes toward sources
      of personal authority (mother, father) were more similar than attitudes toward
      impersonal authority (police, government), though attitudes toward Father were
      related to attitudes toward Government and Police. Age trends showed that younger
      adolescents are more politically conservative and more conforming to authority
      than older adolescents. Results are discussed in terms of the political and
      personological features of Kohlbergian moral judgment and in light of recent
      research on the transformation of adolescent-parent relations in adolescence. 

PMID- 24306954
TI  - Maternal employment and adolescents' relations with parents, siblings, and peers.
AB  - The association between maternal employment status and the relations that
      adolescents have with their parents, siblings, and peers was investigated. Three
      daily reports of conflicts with family members and time spent with parents,
      peers, and alone were obtained from 64 tenth-grade adolescents using a telephone
      interviewing technique. Males, but not females, had more arguments, which were of
      longer duration and greater intensity, with their mothers and siblings when their
      mothers worked than when they did not. Female conflict behavior was unrelated to
      the work status of the mother. Adolescents of both sexes spent less time with
      their parents when their mothers worked, especially when they worked full-time,
      than when they were nonemployed. Adolescents with employed mothers generally
      spent less free time with their parents than those with nonemployed mothers. Time
      spent with parents in the performance of household tasks was not affected by
      maternal employment status. The need to take a family system perspective in order
      to understand fully the relationship between maternal employment and adolescent
      development was emphasized. 

PMID- 24306955
TI  - Psychopathy and aggression: when paralimbic dysfunction leads to violence.
AB  - Psychopaths can be alarmingly violent, both in the frequency with which they
      engage in violence and the gratuitous extent of their violent acts. Indeed, one
      principal utility of the clinical construct of psychopathy is in predicting
      future violent behavior in criminal offenders. Aggression is a complex construct
      that intersects psychopathy at many levels. This chapter provides a review of
      psychopathy as a clinical construct including the most prominent cognitive and
      neurobiological models, which serve to account for its pathophysiology. We then
      describe how the brain abnormalities implicated in psychopathy may lead to
      diverse behavioral outcomes, which can include aggression in its many forms. 

PMID- 24306956
TI  - FGFR2, HER2 and cMet in gastric adenocarcinoma: detection, prognostic
      significance and assessment of downstream pathway activation.
AB  - Receptor tyrosine kinase pathways are potential therapeutic targets in gastric
      adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2
      gene amplification to assess their prognostic significance, and downstream
      mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers
      in patients with gastric adenocarcinoma. Tissue microarrays were constructed from
      resection samples of 184 patients who underwent surgery for gastric/gastro
      oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour
      body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical
      and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2
      amplification was identified in 2 % of cases and associated with worse survival
      (P = 0.005). HER2 overexpression was observed in 10 % of cases and associated
      with increased survival (P = 0.041). cMet overexpression was observed in 4 % of
      cases and associated with worse survival (P < 0.001). On multivariate analysis,
      only cMet retained significance (P = 0.006). pS6 and pERK expression were
      observed in 73 % and 30 % of tumours, respectively, with no association with
      survival. HER2 (P = 0.004) and pERK (P = 0.001) expression differed between
      tumour regions with HER2 expression increased in the LS compared with the TB and
      IE. These findings confirm subpopulations in gastric adenocarcinoma with poor
      outcome that may benefit from specific therapeutic strategies. However, we found
      heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for
      their use as predictive biomarkers in gastric biopsies. The potential downstream
      pharmacodynamic markers pS6 and pERK were expressed across tumour regions,
      providing evidence that resections and biopsies would yield comparative results
      in clinical trials. 

PMID- 24306957
TI  - Expression of miRNAs and ZEB1 and ZEB2 correlates with histopathological grade in
      papillary urothelial tumors of the urinary bladder.
AB  - Histopathological grading of papillary urothelial tumors (PUTs) of the urinary
      bladder is subjective and poorly reproducible. We investigated the relationship
      between the expression of frequently deregulated microRNAs (miRNAs) as well as
      their target genes (ZEB1/ZEB2) and bladder cancer histopathological grade in an
      attempt to find a miRNA that might allow more reliable grading of PUTs. We
      measured the expression levels of four miRNAs (miR-145, miR-205, miR-125b, and
      miR-200c) in 120 formalin-fixed, paraffin-embedded bladder tumor tissue samples
      using real-time PCR assays. ZEB1 and ZEB2 expression was assessed in the same
      bladder tissues by immunohistochemistry. MiR-205 distinguished low-grade
      papillary urothelial carcinoma (LG) from high-grade papillary urothelial
      carcinoma (HG), and miR-145 distinguished HG from infiltrating carcinoma (CA)
      with an area under the receiver operator characteristic curve (AUC) of 0.992 and
      0.997, respectively (sensitivity/specificity of 95.8/96.7 % and 100/91.7 %,
      respectively; p < 0.05). The expression level of miR-125b was significantly lower
      in LG than in PUNLMP, with an AUC value of 0.870 (93.3 % sensitivity and 84.2 %
      specificity; p < 0.05). ZEB1 immunoreactivity was more frequently detected in HG
      than in LG (57 % vs 13 %, p < 0.01) and in HG than in CA (57 % vs 17 %, p <
      0.01). ZEB2 immunoreactivity was more frequent in CA than in HG (83 % vs 54 %, p
      < 0.05). ZEB1/ZEB2 and miRNAs expression seems to reliably distinguish between
      different grades of PUTs of the urinary bladder. They might well serve as useful
      complementary diagnostic biomarkers for grading of papillary urothelial tumors. 

PMID- 24306958
TI  - The density of CD8+ T-cell infiltration and expression of BCL2 predicts outcome
      of primary diffuse large B-cell lymphoma of bone.
AB  - Primary bone lymphoma (PBL) comprises 5 % of all extranodal non-Hodgkin's
      lymphomas (NHLs). Diffuse large B-cell lymphoma (DLBCL) accounts for the majority
      of cases, which is the most heterogeneous group of lymphomas. Previous studies
      suggested that besides the tumor cell phenotype, phosphatidylinositol 3
      kinase/acutely transforming retrovirus/mammalian target of rapamycin
      (PI3K/AKT/mTOR) pathway activity and the composition of the immune
      microenvironment of DLBCL influence the clinical behavior of the disease. The aim
      of our study was to determine the relationship between clinical factors, tumor
      cell phenotype, microenvironment, PI3K/AKT/mTOR pathway activity, and disease
      outcome in primary bone diffuse large B-cell lymphoma (PB-DLBCL). We constructed
      tissue-microarrays from 41 cases of PB-DLBCL. To characterize tumor cell
      phenotype, T-cell subsets, macrophages, and PI3K/AKT/mTOR pathway activity
      immunohistochemical stainings were evaluated. Kaplan-Meier survival analysis
      provided evidence that age (<=65), CD3 and CD8+ T cell infiltrations >5 %, low
      BCL2 expression of the tumor cells (<=30 %), and low proliferation index (Ki67 <=
      57 %) were associated with favorable outcome of PB-DLBCL patients. Multivariate
      analysis revealed that CD8+ T cell infiltration >5 % and low BCL2 expression
      (<=30 %) were independent predictors of survival. Increased macrophage
      infiltration (>10 %) showed tendency toward an adverse prognostic effect.
      International prognostic index, tumor cell phenotype (GCB or ABC), MYC protein
      expression, and activation of PI3K/AKT/mTOR pathway had no significant impact on
      survival. However, mTOR activity showed a significant correlation with activated
      B-cell phenotype. We conclude that CD8 and BCL2 expressions are potential
      prognostic markers for PB-DLBCL patients and the PI3K/AKT/mTOR pathway appears to
      be an additional therapeutic target in PB-DLBCL with activated-B-cell phenotype. 

PMID- 24306959
TI  - Effect of high versus low doses of fat and vitamin A dietary supplementation on
      fatty acid composition of phospholipids in mice.
AB  - Dietary fat and vitamin A provide important precursors for potent bioactive
      ligands of nuclear hormone receptors, which regulate various enzymes involved in
      lipid homeostasis, metabolism and inflammation. We determined the effects of
      dietary fat and dietary vitamin A on hepatic expression of two fatty acid
      metabolizing enzymes, elongase 6 (ELOVL6) and stearoyl-coenzyme A desaturase 1
      (SCD1) and the concentration of saturated fatty acids (SAFA) and monounsaturated
      fatty acid (MUFA) of phospholipids in serum and liver. Mice (n = 6) were fed 4
      weeks with diets containing 2, 5 and 25 % of fat or vitamin A (0, 2,500 and
      326,500 RE/kg as retinyl palmitate). MUFAs and SAFAs were measured using GC and
      ESI-MS/MS. Hepatic expression of metabolizing enzymes was determined using QRT
      PCR. ELOVL6 was significantly down-regulated in response to a high-fat diet (p <
      0.001) and significantly up-regulated in response to low-fat diet (p < 0.05).
      SCD1 expression was significantly lower in high- versus low-fat diet (p < 0.05).
      The vitamin A content in the diet did not influence the hepatic expression of
      both enzymes. In plasma, the amounts of MUFAs bound to phospholipids
      significantly decreased in response to a high-fat diet and increased after a low
      fat diet. This tendency was also observed in the liver for various phospholipids
      sub-classes. In summary, this study shows that fat content in the diet has a
      stronger impact than the content of vitamin A on hepatic gene expression of SCD1
      and ELOVL6 and thereby on MUFA and SAFA concentrations in liver and plasma. 

PMID- 24306960
TI  - Reduced expression of folate transporters in kidney of a rat model of folate
      oversupplementation.
AB  - Folic acid is the key one-carbon donor required for de novo nucleotide and
      methionine synthesis. Its deficiency is associated with megaloblastic anemia,
      cancer and various complications of pregnancy. However, its supplementation
      results in reduction of neural tube defects and prevention of several types of
      cancer. The intake of folic acid from fortified food together with the use of
      nutritional supplements creates a state of folate oversupplementation.
      Fortification of foods is occurring worldwide with little knowledge of the
      potential safety and physiologic consequences of intake of such high doses of
      folic acid. So, we planned to examine the effects of acute and chronic folate
      oversupplementation on the physiology of renal folate transport in rats. Male
      Wistar rats were procured and divided into two groups. Rats in group I were given
      semisynthetic diets containing 2 mg folic acid/kg diet (control) and those in
      group II were given folate-oversupplemented rat diet, i.e., 20 mg folic acid/kg
      diet (oversupplemented). Six animals from group I and group II received the
      treatment for 10 days (acute treatment) and remaining six for 60 days (chronic
      treatment). In acute folate-oversupplemented rats, 5-[(14)C]
      methyltetrahydrofolate uptake was found to be significantly reduced, as compared
      to chronic folate-oversupplemented and control rats. This reduction in uptake was
      associated with a significant decrease in the mRNA and protein levels of the
      folate transporters. Results of the present investigation showed that acute
      oversupplementation led to a specific and significant down-regulation of renal
      folate uptake process mediated via transcriptional and translational regulatory
      mechanism(s). 

PMID- 24306964
TI  - Preface.

PMID- 24306965
TI  - Performance of instrumental variable methods in cohort and nested case-control
      studies: a simulation study.
AB  - PURPOSE: Instrumental variable (IV) analysis is becoming increasingly popular to
      adjust for confounding in observational pharmacoepidemiologic research. One of
      the prerequisites of an IV is that it is strongly associated with exposure; if it
      is weakly associated with exposure, IV estimates are reported to be biased. We
      aimed to assess the performance of IV estimates in various (pharmaco
      )epidemiologic settings. METHODS: Data were simulated for continuous/binary
      exposure, outcome and IV in cohort and nested case-control (NCC) designs with
      different incidences of the outcome. Pearson's correlation, point bi-serial
      correlation, odds ratio (OR), and F-statistic were used to assess the IV-exposure
      association. Two-stage analysis was performed to estimate the exposure effect.
      RESULTS: For all types of IV and exposure in the cohort and NCC designs, IV
      estimates were extremely unstable and biased when the IV was very weakly
      associated with exposure (e.g. Pearson's correlation < 0.15 for continuous or OR
      < 2.0 for binary IV and exposure; although specific cut-off values depend on
      simulation settings). For stronger IVs, estimates were unbiased and become less
      variable compared with weaker IVs in the case of continuous and binary (risk
      difference scale) outcomes. For a similar IV-exposure association (e.g. OR = 1.4
      and 5% incidence of the outcome), the variability of the estimates was more
      pronounced in the NCC (standard deviation = 2.37, case : control = 1:5) compared
      with the cohort design (standard deviation = 1.14). The variability was even more
      pronounced for rare (<=1%) outcomes. However, IV estimates from the NCC design
      became less variable with an increasing number of controls per case. Moreover,
      estimates were biased when the IV was related to confounders even with strong
      IVs. CONCLUSIONS: Instrumental variable analysis performs poorly when the IV
      exposure association is extremely weak, especially in the NCC design. IV
      estimates in the NCC design become less variable when the number of control
      increases. As NCC does not use the entire cohort, in order to achieve stable
      estimates, this design requires a stronger IV-exposure association than the
      cohort design.

PMID- 24306962
TI  - Native American ancestry, lung function, and COPD in Costa Ricans.
AB  - BACKGROUND: Whether Native American ancestry (NAA) is associated with COPD or
      lung function in a racially admixed Hispanic population is unknown. METHODS: We
      recruited 578 Costa Ricans with and without COPD into a hybrid case
      control/family-based cohort, including 316 members of families of index case
      subjects. All participants completed questionnaires and spirometry and gave a
      blood sample for DNA extraction. Genome-wide genotyping was conducted with the
      Illumina Human610-Quad and HumanOmniExpress BeadChip kits (Illumina Inc), and
      individual ancestral proportions were estimated from these genotypic data and
      reference panels. For unrelated individuals, linear or logistic regression was
      used for the analysis of NAA and COPD (GOLD [Global Initiative for Chronic
      Obstructive Lung Disease] stage II or greater) or lung function. For extended
      families, linear mixed models and generalized estimating equations were used for
      the analysis. All models were adjusted for age, sex, educational level, and
      smoking behavior; models for FEV1 were also adjusted for height. RESULTS: The
      average proportion of European, Native American, and African ancestry among
      participants was 62%, 35%, and 3%, respectively. After adjustment for current
      smoking and other covariates, NAA was inversely associated with COPD (OR per 10%
      increment, 0.55; 95% CI, 0.41-0.75) but positively associated with FEV1, FVC, and
      FEV1/FVC. After additional adjustment for pack-years of smoking, the association
      between NAA and COPD or lung function measures was slightly attenuated. We found
      that about 31% of the estimated effect of NAA on COPD is mediated by pack-years
      of smoking. CONCLUSIONS: NAA is inversely associated with COPD but positively
      associated with FEV1 or FVC in Costa Ricans. Ancestral effects on smoking
      behavior partly explain the findings for COPD but not for FEV1 or FVC.

PMID- 24306967
TI  - The evolution of progressive postoperative weight bearing after autologous
      chondrocyte implantation in the tibiofemoral joint.
AB  - Autologous chondrocyte implantation (ACI) has demonstrated good clinical success
      in the repair of articular cartilage defects in the knee. Postoperative
      rehabilitation after ACI is considered critical in returning the patient to an
      optimal level of function by attempting to create the appropriate mechanical
      environment for cartilage regrowth, and it involves a progressive program that
      emphasizes full motion, progressive partial weight bearing (PWB), and controlled
      exercises. While evidence-based research is clearly lacking in all components of
      ACI rehabilitation, one important element in this treatment algorithm that has
      been subjected to some early scientific study is the gradual progression of the
      patient back to full weight-bearing (WB) gait after surgery. With the continual
      advancement of ACI surgical techniques, along with clinical experience and
      improved knowledge of histology and of the maturation process of chondrocytes,
      proposed postoperative WB protocols have evolved to better reflect the nature of
      the specific ACI surgery. The purpose of this article is to present the varied
      PWB programs that have been practiced alongside the evolving ACI surgical
      technique, the experimental basis for such protocols, the issues pertinent to the
      accurate prescription of WB, and future directions for developing such methods to
      best return patients to an optimal level of function after ACI. 

PMID- 24306966
TI  - Authoritative parenting and cigarette smoking among multiethnic preadolescents:
      the mediating role of anti-tobacco parenting strategies.
AB  - INTRODUCTION: Parenting has been shown to affect smoking among children in U.S.
      majority groups, but less is known about this association among multiethnic urban
      populations. Our study examines the role of parenting on smoking among a highly
      diverse sample. METHODS: Health surveys were collected from eighth graders (N =
      459) in 2 low-income urban schools. Structural equation models examined the
      direct and indirect effects of authoritative parenting on lifetime smoking. A
      moderated mediation analysis examined whether indirect effects of authoritative
      parenting vary among racial/ethnic groups. RESULTS: Authoritative controlling
      parenting, characterized by limit setting, was positively associated with anti
      tobacco parenting. Anti-tobacco parenting was inversely associated with smoking,
      mediating the relationship between controlling parenting and smoking. There was
      no evidence that mediation was moderated by race/ethnicity. CONCLUSIONS: Parent
      training, which focuses on setting rules and expectations, can be an important
      and universal element of smoking prevention programs targeted to youth in diverse
      communities.

PMID- 24306961
TI  - Cellular polarity in aging: role of redox regulation and nutrition.
AB  - Cellular polarity concerns the spatial asymmetric organization of cellular
      components and structures. Such organization is important not only for biological
      behavior at the individual cell level, but also for the 3D organization of
      tissues and organs in living organisms. Processes like cell migration and
      motility, asymmetric inheritance, and spatial organization of daughter cells in
      tissues are all dependent of cell polarity. Many of these processes are
      compromised during aging and cellular senescence. For example, permeability
      epithelium barriers are leakier during aging; elderly people have impaired
      vascular function and increased frequency of cancer, and asymmetrical inheritance
      is compromised in senescent cells, including stem cells. Here, we review the
      cellular regulation of polarity, as well as the signaling mechanisms and
      respective redox regulation of the pathways involved in defining cellular
      polarity. Emphasis will be put on the role of cytoskeleton and the AMP-activated
      protein kinase pathway. We also discuss how nutrients can affect polarity
      dependent processes, both by direct exposure of the gastrointestinal epithelium
      to nutrients and by indirect effects elicited by the metabolism of nutrients,
      such as activation of antioxidant response and phase-II detoxification enzymes
      through the transcription factor nuclear factor (erythroid-derived 2)-like 2
      (Nrf2). In summary, cellular polarity emerges as a key process whose redox
      deregulation is hypothesized to have a central role in aging and cellular
      senescence. 

PMID- 24306969
TI  - Editors' note.

PMID- 24306968
TI  - The importance of biotic interactions and local adaptation for plant response to
      environmental changes: field evidence along an elevational gradient.
AB  - Predicting the response of species to environmental changes is a great and on
      going challenge for ecologists, and this requires a more in-depth understanding
      of the importance of biotic interactions and the population structuration in the
      landscape. Using a reciprocal transplantation experiment, we tested the response
      of five species to an elevational gradient. This was combined to a neighbour
      removal treatment to test the importance of local adaptation and biotic
      interactions. The trait studied was performance measured as survival and biomass.
      Species response varied along the elevational gradient, but with no consistent
      pattern. Performance of species was influenced by environmental conditions
      occurring locally at each site, as well as by positive or negative effects of the
      surrounding vegetation. Indeed, we observed a shift from competition for biomass
      to facilitation for survival as a response to the increase in environmental
      stress occurring in the different sites. Unlike previous studies pointing out an
      increase of stress along the elevation gradient, our results supported a stress
      gradient related to water availability, which was not strictly parallel to the
      elevational gradient. For three of our species, we observed a greater biomass
      production for the population coming from the site where the species was dominant
      (central population) compared to population sampled at the limit of the
      distribution (marginal population). Nevertheless, we did not observe any pattern
      of local adaptation that could indicate adaptation of populations to a particular
      habitat. Altogether, our results highlighted the great ability of plant species
      to cope with environmental changes, with no local adaptation and great
      variability in response to local conditions. Our study confirms the importance of
      taking into account biotic interactions and population structure occurring at
      local scale in the prediction of communities' responses to global environmental
      changes. 

PMID- 24306970
TI  - Introduction.

PMID- 24306971
TI  - Significance of phototoxic phytochemicals in insect herbivory.
AB  - The significance of the wide range of phototoxins, occurring in many plant
      species, with respect to their role in insect herbivory and on insects, is not
      fully understood. The types of compounds include polyacetylenes, quinones,
      furanocoumarins, tryptophan- and tyrosine-derived alkaloids and are distributed
      throughout some of the major families of flowering plants. Efforts are being made
      to determine the mechanisms of cellular toxicity of these compounds at the
      cellular and the organismal levels. 

PMID- 24306972
TI  - Toxicological action and ecological importance of plant photosensitizers.
AB  - This review discusses the biochemical action and ecological significance of
      phototoxic phytochemicals. Mechanistic details of photosensitization as well as
      cellular and molecular targets of plant-derived phototoxins in model biological
      systems (microbial and in vitro) and in herbivorous insects are described.
      Findings from these studies suggest the potential importance of phototoxic plant
      metabolites in plant-insect interactions. Aspects of phototoxin distribution and
      significance in diverse ecosystems are considered, and areas for future research
      are suggested. 

PMID- 24306973
TI  - Light-mediated allelochemical effects of naturally occurring polyacetylenes and
      thiophenes from asteraceae on herbivorous insects.
AB  - Polyacetylenes and their thiophene derivatives, characteristic secondary
      metabolites of the Asteraceae, were examined for their effects on herbivorous
      insects. Three thiophenes (a monothiophene, a bithiophene, and alpha-terthienyl)
      and four polyacetylenes (phenylheptatriyne, phenylheptadiynene, phenylheptadiyene
      acetate, and matricaria lactone) were studied for their phototoxicity and light
      independent toxicity to (1) a polyphagous lepidopteran,Ostrinia nubilalis, whose
      host range includes a number of phototoxic Asteraceae, (2) a polyphagous
      lepidoteran,Euxoa messoria, whose host range includes very few species of
      Asteraceae, and (3) an oligophagous lepidopteran,Manduca sexta, which is a
      specialist on Solanaceae. Several compounds were phototoxic toM. sexta andE.
      messoria even at very low irradiance levels, but behavioral adaptations,
      including spinning silk and boring into diet, allowedO. nubilalis to avoid
      photosensitization. Light-independent activity of the compounds to all three
      species involved feeding deterrence increasing in the orderO. nubilalis, E.
      messoria, andM. sexta, and longterm metabolic toxicity in the form of impaired
      nutrient utilization. The biosynthetically derived thiophenes were more toxic
      than their acetylenic precursors, and toxicity increased with increasing number
      of thiophene rings. The results are discussed in terms of plant-insect
      coevolution. 

PMID- 24306974
TI  - Insect defenses against phototoxic plant chemicals.
AB  - In addition to avoidance strategies, insects may use one or more biochemical
      defenses against phototoxic plant constituents or the reactive forms of oxygen
      they generate. These biochemical defenses may include metabolism; excited state
      quenching; deactivation of singlet oxygen, superoxide, or free radicals; and
      destruction of reaction products. This article is a survey of the antioxidative
      enzymes and simpler molecules produced by insects and their possible roles in
      combating phototoxic chemicals. 

PMID- 24306975
TI  - Comparative metabolism of [(3)H]psoralen and [ (3)H]isopsoralen by black
      swallowtail (Papilio polyxenes Fabr.) caterpillars.
AB  - The comparative fate of tritiated preparations of a linear furanocoumarin
      (psoralen) and an angular furanocoumarin (isopsoralen) was determined in last
      instar caterpillars of the black swallowtail butterfly (Papilio polyxenes Fabr.).
      Oral administration of either furanocoumarin at 5 MUg/g is followed by rapid
      metabolism, primarily through oxidative cleavage of the furan ring, and the
      metabolites are rapidly excreted. Isopsoralen is, however, metabolized at a
      somewhat slower rate than is psoralen, and levels of unmetabolized isopsoralen in
      body tissues of the treated caterpillars are about three-fold higher. These data
      are compatible with the hypothesis that a reduced detoxification rate accounts at
      least in part for the susceptibility ofP. polyxenes caterpillars to the
      deleterious effect of isopsoralens. 

PMID- 24306976
TI  - In vitro metabolism of a linear furanocoumarin (8-methoxypsoralen, xanthotoxin)
      by mixed-function oxidases of larvae of black swallowtail butterfly and fall
      armyworm.
AB  - Studies were made of the comparative in vitro metabolism of [(14)C]xanthotoxin
      and [(14)C]aldrin by homogenate preparations of midguts and bodies (carcass minus
      digestive tract and head) of last-stage larvae of the black swallowtail butterfly
      (Papilio polyxenes Fabr.) and the fall armyworm [Spodoptera frugiperda (J. E.
      Smith)]. The two substrates were metabolized by 10,000g supernatant microsomal
      preparations from both species. Evidence gained through the use of a specific
      inhibitor and cofactor indicated that mixed-function microsomal oxidases were
      major factors in the metabolism and that the specific activity of this enzyme
      system was considerably higher in midgut preparations fromP. polyxenes than in
      similar preparations fromS. frugiperda. Aldrin was metabolized 3-4 times faster
      byP. polyxenes, and xanthotoxin 6-6.5 times faster. 

PMID- 24306977
TI  - Efficacy of the plant phototoxinalpha-terthienyl againstAedes intrudens and
      effects on nontarget organisms.
AB  - The botanical phototoxin, alpha-terthienyl (alpha-T) was spray applied to natural
      or artificial pools containing mosquito (Aedes intrudens) larvae and nontarget
      invertebrates (caddisfly, damselfly, midge, shrimp,Daphnia, snail) and one
      vertebrate (trout) at concentrations varying from 0.01 to 1 kg/hectare, under
      field and laboratory conditions. All field-treated nontarget invertebrates
      survived alpha-T treatment better thanA. intrudens which can be controlled at
      doses as low as 0.01 kg/hectare within one week. Under laboratory conditions,
      snails and trout survived alpha-T and UV treatments up to 10 kg/ hectare. These
      results compare favorably with organophosphates and pyrethroid insecticides
      currently used for mosquito control. The results confirm that alpha-T is a highly
      effective larvicide with acceptable nontarget effects. 

PMID- 24306978
TI  - Delayed phototoxic effects of 8-methoxypsoralen, khellin, and sphondin inAedes
      aegypti.
AB  - At concentrations up to 6.7 ppm, 8-methoxypsoralen, sphondin, and khellin are not
      toxic to first-instar larvae of the mosquitoAedes aegypti. The irradiation of
      sensitized larvae with long-wavelength ultraviolet light did not always produce
      any immediate toxicity enhancement, but delayed effects were clearly visible.
      These were observed over the development of the organisms from first-instar
      larvae to adults. No adverse effects were noted when larvae were irradiated in
      the absence of sensitizers, or when they were placed in solutions of sensitizers
      which had been previously irradiated with the same light sources. 8
      Methoxypsoralen was slightly more phototoxic than its isomer sphondin. Khellin,
      recently reported to undergo photoinduced cyclization with DNA components, showed
      minimal phototoxicity in the concentration range used. 

PMID- 24306979
TI  - Detection of furocoumarins in plants and plant products with an ultrasensitive
      biological photoassay employing a DNA-repair-deficient bacterium.
AB  - The application of an ultrasensitive photobiological assay which detects
      photosensitizing furocoumarins with sensitivities as high as 1 * 10(-11) g is
      discussed in relation to these molecules as phytoalexins. Examples of the
      utilization of this technique, verified by both HPLC and TLC, are the analyses of
      healthy and diseased celery and carrots, dry seeds, plant extracts and oils, and
      whole plants and leaves. The usefulness of this method in following the metabolic
      detoxification of furocoumarins is also illustrated. The extreme sensitivity of
      the test has permitted the detection, for the first time, of both 5
      methoxypsoralen and 8-methoxypsoralen in fresh carrot roots. 

PMID- 24306980
TI  - Inactivation and mutagenesis by phototoxins usingEscherichia coli strains
      differing in sensitivity to near- and far-ultraviolet light.
AB  - FourEscherichia coli strains carrying all the possible combinations of genes
      controlling sensitivity to near-UV (NUV;nur versusnur (+)) and far-UV (FUV;uvrA6
      versusuvrA (+)) were inactivated with broad-spectrum NUV together with specific
      phototoxins. The inactivation kinetics of the four strains are consistent with
      the previous reports that psoralen and angelicin inactivation is based on the
      formation of DNA adducts, while xanthotoxin (8-MOP) inactivation is based on the
      combined effects of DNA adduct formation and oxygen-dependent photodynamic
      action. At sufficiently high NUV fluences, xanthotoxol (8-HOP) induces lethal DNA
      lesions in an excision-deficient (uvrA6) strain. Inactivation by alpha-terthienyl
      plus NUV involves strictly membrane damage since the genes controlling the
      sensitivity to either NUV or FUV have no effect on inactivation kinetics. Using
      mutation to histidine independence (his-4 (+)) in the presence of NUV as a
      measure of mutagenicity by phototoxins, psoralen and xanthotoxin are mutagenic,
      angelicin is less mutagenic, and xanthotoxol and alpha-terthienyl are not
      mutagenic. None of the phototoxins tested in the presence of NUV were as
      mutagenic as FUV. Imperatorin and berberine were neither phototoxic nor mutagenic
      in this assay system. This assay thus provides a rapid qualitative screening
      procedure to identify the mode of action and mutagenicity of plant phototoxins
      with potential insecticidal properties. 

PMID- 24306981
TI  - Regional models for sediment toxicity assessment.
AB  - The present study describes approaches to improve the performance of empirical
      models developed from a large nationwide data set to predict sediment toxicity
      from chemistry for regional applications. The authors developed 4 multiple
      chemical (PMax ) models selected from individual chemical models developed using
      1) a previously published approach applied to the nationwide data set; 2) a
      broader array of response and explanatory variables (e.g., different
      normalization approaches and toxicity classifications) applied to the nationwide
      data set; 3) a data set from the New York/New Jersey, USA, region; and 4) both
      nationwide and regional data sets. The models were calibrated using the regional
      data set. Performance was tested using an independent data set from the same
      region. The performance of the final PMax model developed using the calibration
      process substantially improved over that of the uncalibrated PMax model developed
      using the nationwide data set. The improvements were achieved by selecting the
      best performing individual chemical models and eliminating those that performed
      poorly when applied together. Although the best performing PMax model included
      both nationwide and region-specific models, the performance of the PMax model
      derived using only nationwide models was nearly as good. These results suggest
      that calibrating nationwide models to a regional data set may be both a more
      efficient and effective approach for improving model performance than developing
      region-specific models. This article is a US Government work and is in the public
      domain in the USA.

PMID- 24306982
TI  - Searching the same display twice: Properties of short-term memory in repeated
      search.
AB  - Consecutive search for different targets in the same display is supported by a
      short-term memory mechanism: Distractors that have recently been inspected in the
      first search are found more quickly in the second search when they become the
      target (Exp. 1). Here, we investigated the properties of this memory process. We
      found that this recency advantage is robust to a delay between the two searches
      (Exp. 2) and that it is only slightly disrupted by an interference task between
      the two searches (Exp. 3). Introducing a concurrent secondary task (Exp. 4)
      showed that the memory representations formed in the first search are based on
      identity as well as location information. Together, these findings show that the
      short-term memory that supports repeated visual search stores a complex
      combination of item identity and location that is robust to disruption by either
      time or interference.

PMID- 24306984
TI  - Weightlifting exercise and the size-weight illusion.
AB  - In the size-weight illusion (SWI), large objects feel lighter than equally
      weighted small objects. In the present study, we investigated whether this
      powerful weight illusion could influence real-lift behavior-namely, whether
      individuals would perform more bicep curls with a dumbbell that felt subjectively
      lighter than with an identically weighted, but heavier-feeling, dumbbell.
      Participants performed bicep curls until they were unable to continue with both a
      large, light-feeling 5-lb dumbbell and a smaller, heavy-feeling 5-lb dumbbell. No
      differences emerged in the amounts of exercise that participants performed with
      each dumbbell, even though they felt that the large dumbbell was lighter than the
      small dumbbell. Furthermore, in a second experiment, we found no differences in
      how subjectively tired participants felt after exercising for a set time with
      either dumbbell. We did find, however, differences in the lifting dynamics, such
      that the small dumbbell was moved at a higher average velocity and peak
      acceleration. These results suggest that the SWI does not appear to influence
      exercise outcomes, suggesting that perceptual illusions are unlikely to affect
      one's ability to persevere with lifting weights.

PMID- 24306983
TI  - Beyond slots and resources: grounding cognitive concepts in neural dynamics.
AB  - Research over the past decade has suggested that the ability to hold information
      in visual working memory (VWM) may be limited to as few as three to four items.
      However, the precise nature and source of these capacity limits remains hotly
      debated. Most commonly, capacity limits have been inferred from studies of visual
      change detection, in which performance declines systematically as a function of
      the number of items that participants must remember. According to one view, such
      declines indicate that a limited number of fixed-resolution representations are
      held in independent memory "slots." Another view suggests that such capacity
      limits are more apparent than real, but emerge as limited memory resources are
      distributed across more to-be-remembered items. Here we argue that, although both
      perspectives have merit and have generated and explained impressive amounts of
      empirical data, their central focus on the representations--rather than processes
      -underlying VWM may ultimately limit continuing progress in this area. As an
      alternative, we describe a neurally grounded, process-based approach to VWM: the
      dynamic field theory. Simulations demonstrate that this model can account for key
      aspects of behavioral performance in change detection, in addition to generating
      novel behavioral predictions that have been confirmed experimentally.
      Furthermore, we describe extensions of the model to recall tasks, the integration
      of visual features, cognitive development, individual differences, and functional
      imaging studies of VWM. We conclude by discussing the importance of grounding
      psychological concepts in neural dynamics, as a first step toward understanding
      the link between brain and behavior.

PMID- 24306986
TI  - Leghemoglobin-like sequences in the DNA of four actinorhizal plants.
AB  - A cloned cDNA partial copy of a soybean leghemoglobin mRNA was used to probe
      genomic DNA of four species of actinorhizal plants. Southern blot hybridization
      revealed the presence of sequences with homology to the leghemoglobin probe in
      DNA from Alnus glutinosa, Casuarina glauca, Ceanothus americanus and Elaeagnus
      pungens. The hybridization patterns of the restriction fragments revealed some
      fragment size conservation between the DNA of soybean and the DNA of four
      actinorhizal plants which are taxonomically unrelated to soybean or to each
      other. The results presented here indicate that globin gene sequences are much
      more widely distributed in the plant kingdom than has previously been thought.
      Furthermore, if sequence conservation is actually as high as the restriction
      fragment patterns suggest, the evolution of the DNA surrounding the globin
      sequences has been highly constrained. 

PMID- 24306985
TI  - Response inhibition during perceptual decision making in humans and macaques.
AB  - Response inhibition in stop signal tasks has been explained as the outcome of a
      race between GO and STOP processes (e.g., Logan, 1981). Response choice in two
      alternative perceptual categorization tasks has been explained as the outcome of
      an accumulation of evidence for the alternative responses. To begin unifying
      these two powerful investigation frameworks, we obtained data from humans and
      macaque monkeys performing a stop signal task with responses guided by perceptual
      categorization and variable degrees of difficulty, ranging from low to high
      accuracy. Comparable results across species reinforced the validity of this
      animal model. Response times and errors increased with categorization difficulty.
      The probability of failing to inhibit responses on stop signal trials increased
      with stop signal delay, and the response times for failed stop signal trials were
      shorter than those for trials with no stop signal. Thus, the Logan race model
      could be applied to estimate the duration of the stopping process. We found that
      the duration of the STOP process did not vary across a wide range of
      discrimination accuracies. This is consistent with the functional, and possibly
      mechanistic, independence of choice and inhibition mechanisms.

PMID- 24306987
TI  - Intracellular sites of the synthesis of sweet potato mitochondrial F1ATPase
      subunits.
AB  - Five subunits (alpha-, beta-, gamma-, delta- and delta'-subunits) of the six
      alpha~delta'-and epsilon-subunits) in the F1 portion (F1ATPase) of sweet potato
      (Ipomoea batatas) mitochondrial adenosine triphosphatase were isolated by an
      electrophoretic method. The delta- and delta'-subunits were not distinguishable
      immunologically but showed completely different tryptic peptide maps, indicating
      that they were different molecular species. In vitro protein synthesis with
      isolated sweet potato root mitochondria produced only the alpha-subunit when
      analyzed with anti-sweet potato F1ATPase antibody reacting with all the subunits
      except the epsilon-subunit. Sweet potato root poly(A)(+)RNA directed the
      synthesis of six polypeptides which were immunoprecipitated by the antibody: two
      of them immunologically related to the beta-subunit and the others to the delta-
      and delta'-subunits. We conclude that the alpha-subunit of the F1ATPase is
      synthesized only in the mitochondria and the beta-, delta- and delta'-subunits
      are in the cytoplasm. 

PMID- 24306988
TI  - Sequences of two bean mitochondria tRNAs(Tyr) which differ in the level of post
      transcriptional modification and have a prokaryotic-like large extra-loop.
AB  - Two bean mitochondrial tRNAs(Tyr) purified by RPC-5 chromatography and two
      dimensional gel electrophoresis have been sequenced using post-labeling
      techniques. These two tRNAs only differ by three post-transcriptional
      modifications in the D-loop. They have a large variable loop and therefore
      resemble prokaryotic tRNAs(Tyr) rather than eukaryotic cytoplasmic tRNAs(Tyr). 

PMID- 24306989
TI  - Extrachromosomal DNA of pea-root (Pisum sativum) has repeated sequences and
      ribosomal genes.
AB  - Restriction endonuclease digestion and Southern blotting procedure were used to
      determine differences between extrachromosomal, nuclear, plastid, and
      mitochondrial DNAs from meristematic cells of cultured pea roots.Extrachromosomal
      and nuclear DNA are highly methylated and neither DNA is homologous to plastid or
      mitochondrial DNA. Hybridization of extrachromosomal DNA to nuclear DNA indicated
      that extrachromosomal DNA differed quantitatively from total nuclear DNA in
      repetitive sequences. Cloned rDNA showed that extrachromosomal DNA contains rRNA
      genes but the hybridization signal indicated that the copy number was less than
      that expected if the molecules were amplified. These and cytological findings
      suggest that extrachromosomal DNA is involved in or a product of genomic changes
      associated with the onset of differentiation by precursor cells of vascular
      parenchyma and the root cap. 

PMID- 24306990
TI  - Dihydrofolate reductase from Daucus carota cell suspension cultures:
      purification, molecular and kinetic characterization.
AB  - The purification of dihydrofolate reductase (5, 6, 7, 8 tetrahydrofolate: NADP(+)
      oxidoreductase, E.C.: 1.5.1.3) from Daucus carota to apparent homogeneity, is
      described. The enzyme is a soluble protein with a molecular weight of 183 000+/-2
      500, composed of identical subunits of 58 400+/-1 000. The enzyme is only weakly
      recognized by antibodies against human DHFR. The carrot DHFR is characterized by
      a pH optimum of 5.9, Km values for dihydrofolate and NADPH of 3.7 MUM and 2.2
      MUM, respectively and a turnover number of 4 750 or 1 500 when referring to the
      183 K form or the 58 K monomer, respectively. Molecular and kinetic properties
      are remarkably different from those reported for the soybean enzyme. Sensitivity
      to methotrexate is similar to that of bacterial and mammalian enzymes while
      sensitivity to trimethoprim and dihydrotriazine is intermediate between the two
      groups of organisms. 

PMID- 24306991
TI  - Plastid gene expression during fruit ripening in tomato.
AB  - A tomato chloroplast genome map has been constructed with the restriction enzymes
      Hpa I, Pvu II, and Sal I. Twelve plastid genes have been located on the tomato
      plastid genome (159 kb).The expression of plastid genes during tomato fruit
      ripening has been studied. The levels of transcripts of various genes coding for
      proteins of the photosystem I (psaA), photosystem II (psbA, psbB, psbC, psbD) and
      the stroma (rbcL) decrease when plastids differentiate from chloroplasts to
      chromoplasts. The amount of plastid ribosomal RNA also decreases. Transcripts of
      the genes for the P700 reaction center protein (psaA), for the photosystem II
      associated proteins (psbC, psbD) and for the large subunit of ribulose-1,5
      bisphosphate carboxylase (rbcL) cannot be detected in chromoplasts. In contrast,
      a relatively high level of mRNA is present for the 32 kD protein ('herbicide
      binding protein', psbA) in red fruit. 

PMID- 24306992
TI  - Identification of the genetic locus responsible for non-polar root induction by
      Agrobacterium rhizogenes 1855.
AB  - Root proliferation can be induced by Agrobacterium rhizogenes on carrot discs
      both on the apical and basal surface (facing the root apex and base,
      respectively) or on the apical surface only, depending on the bacterial strain.
      This differential response on the two surfaces is denominated polarity. We
      correlate the polarity of some strains with the absence of an Ri plasmid genetic
      locus, present in non polar strains such as A. rhizogenes 1855, which bears
      sequence homology with the auxin genes of Ti plasmid T-DNA. We demonstrate that
      this locus is responsible for root induction on the basal surface since insertion
      of a transposon in this region of pRi1855 induces polarity in this strain. 

PMID- 24306993
TI  - Interleukin-22, liver progenitor cells, and liver cancer.

PMID- 24306994
TI  - Social media in disaster risk reduction and crisis management.
AB  - This paper reviews the actual and potential use of social media in emergency,
      disaster and crisis situations. This is a field that has generated intense
      interest. It is characterised by a burgeoning but small and very recent
      literature. In the emergencies field, social media (blogs, messaging, sites such
      as Facebook, wikis and so on) are used in seven different ways: listening to
      public debate, monitoring situations, extending emergency response and
      management, crowd-sourcing and collaborative development, creating social
      cohesion, furthering causes (including charitable donation) and enhancing
      research. Appreciation of the positive side of social media is balanced by their
      potential for negative developments, such as disseminating rumours, undermining
      authority and promoting terrorist acts. This leads to an examination of the
      ethics of social media usage in crisis situations. Despite some clearly
      identifiable risks, for example regarding the violation of privacy, it appears
      that public consensus on ethics will tend to override unscrupulous attempts to
      subvert the media. Moreover, social media are a robust means of exposing
      corruption and malpractice. In synthesis, the widespread adoption and use of
      social media by members of the public throughout the world heralds a new age in
      which it is imperative that emergency managers adapt their working practices to
      the challenge and potential of this development. At the same time, they must heed
      the ethical warnings and ensure that social media are not abused or misused when
      crises and emergencies occur.

PMID- 24306995
TI  - pH-responsive micro- and nanocarrier systems.
AB  - Release on demand: The pH gradients between extra- and intracellular regions can
      be utilized for the controlled release of drugs and biological cargos from
      delivery systems. Biocompatible carrier systems with pH-cleavable units must
      fulfill many other criteria as well, for example, a long blood circulation time.
      This can be achieved by tailored micro- and nanocarriers based on macromolecular
      architectures or stable self-assembled systems. 

PMID- 24306996
TI  - A straightforward treatment of activity in aqueous CaCO3 solutions and the
      consequences for nucleation theory.
AB  - The aqueous calcium carbonate system is rigorously investigated with respect to
      ionic activity. Ideal treatment is found to be a good approximation at relevant
      concentrations. The data further show that bound CaCO3 species cannot be regarded
      as "inactive" during nucleation but rather appear to play a key role in the phase
      separation process, and that amorphous calcium carbonate (ACC) can be
      precipitated from much lower levels of supersaturation than previously believed. 

PMID- 24306997
TI  - On being present-minded.

PMID- 24306998
TI  - Psychotherapy and religion: The emmanuel movement.
AB  - This paper reconsiders the significance of the Emmanuel movement, a pre- Freudian
      psychotherapeutic system founded by Dr. Elwood Worcester as a method of church
      sponsored healing. Its significance lies in three areas: (1) Historically, it was
      a popular effort by Protestant clergy to claim religious authority over
      psychological and psychosomatic ailments, a struggle that the medical profession
      eventually won almost completely. (2) The Emmanuel movement was an effort to
      combat the scientific materialism and medical somaticism of its time, including
      the excessive use of drugs. It aimed at greater individual control over emotional
      wellbeing through a self-help movement taught by religious leaders using some
      Christian ideas. Significant parallels can be found with present-day holistic
      health efforts. (3) Theoretically, Worcester's conception of the "person" is of
      interest as an effort to construct a nonreductionist view of the interactions of
      body, mind, and spirit. 

PMID- 24306999
TI  - The legacy of Kohut for religion and psychology.

PMID- 24307000
TI  - Sexuality and spirit in Kierkegaard's thought.
AB  - The following article shows a sensible and responsible interpretation of
      Kierkegaard's theory of sexuality in relation to the longest-range development of
      self, where self from this perspective will be called spirit. Since, for
      Kierkegaard, this longest-range development involved immortality and was
      construed by him from a religious perspective, the topics under consideration
      will necessarily have some relevance to the philosophy of religion. Mental health
      issues will figure prominently, too. In the process of working this out, I have
      found some startling and significant adumbrations of some of Freud's work. 

PMID- 24307001
TI  - Christian commitment and a "Docetic" view of human emotions.
AB  - This paper encourages people in the church to discuss the danger of equating
      Christian commitment with a denial of one's humanity, thus developing a "docetic"
      view of human emotions. The paper focuses on biblical passages which are
      susceptible to three forms of "docetic interpretation":denial of unpleasant
      feelings often in the name of Christian joy, with possible damaging emotional or
      physical consequences;denial of human development and the possible influence of
      the past on present emotional and religious experience; anddenial of human value
      through passive acceptance of what seems to be inevitable by saying, "Thy will be
      done." 

PMID- 24307002
TI  - Pastoral accompaniment of the cancer patient.
AB  - Cancer confronts a person with his or her mortality. On the inner journey of
      coming to terms with this, the pastor accompanies the patient in a way analogous
      to the way in which a musical accompanist supports a soloist, providing attentive
      relationship and supportive context. Patients in these circumstances raise and
      explore themes of betrayal-faithfulness, control-surrender, despair-hope, and
      separation-reconciliation. 

PMID- 24307003
TI  - Near-death experiences and religion: A further investigation.
AB  - The relationship between religion and near-death experiencers (NDEs) was examined
      by interviewing 40 near-death experiences who were given a series of instruments
      to measure religious orientation and religious change. No relationship was found
      between religious orientation prior to the NDE and the depth of the NDE. However,
      a significant correlation was found between the depth of the NDE and a subsequent
      increase both in the importance of religion and in religious activity. Various
      theoretical explanations of NDEs were examined to account for these findings. 

PMID- 24307004
TI  - The inside story. Physicians' views on digital ano-rectal examination for anal
      cancer screening of HIV positive men who have sex with men.
AB  - OBJECTIVE: Anal cancer is relatively common amongst HIV positive men who have sex
      with men (MSM), but little is known about the anal cancer screening practices of
      HIV physicians, and whether digital ano-rectal examination (DARE) is utilized for
      this. To determine the practice of anal cancer screening among HIV physicians,
      and to identify any barriers for implementing DARE as a method for anal cancer
      screening. METHODS: 36 physicians from a sexual health centre, 2 tertiary
      hospital infectious diseases outpatient clinics, and 2 general practices
      completed a questionnaire on their practice of anal cancer screening amongst HIV
      positive MSM. Physicians were asked about their confidence in using DARE for anal
      cancer screening, and whether they perceived barriers to implementing this in
      their clinic. RESULTS: Most physicians (86%, 95% CI: 71-95) thought that anal
      cancer screening was important, but only 22% (95% CI: 10-39) were currently
      screening. Reasons for not screening were the absence of guidelines (87%, 95% CI:
      60-98), lack of time (47%, 95% CI: 30-65), and concern about patient
      acceptability of DARE (32%, 95% CI: 17-51). Whilst 67% (95% CI: 49-81) of
      physicians felt confident in performing a DARE, only 22% (95% CI: 10-39) were
      confident in recognizing anal cancer using DARE. CONCLUSION: Although HIV
      physicians were aware of the need for anal cancer screening among the HIV + MSM
      population, few were routinely screening. If DARE were to be incorporated into
      routine HIV care, guidelines recommending screening and up-skilling of HIV
      physicians to recognize anal cancer are needed.

PMID- 24307005
TI  - The neurology of Sjogren's syndrome and the rheumatology of peripheral neuropathy
      and myelitis.
AB  - Neurological symptoms occur in approximately 20% of patients with Sjogren's
      syndrome, and may be the presenting manifestations of the disease. Here, we
      review several neurological conditions that can occur in Sjogren's syndrome:
      sensory ganglionopathy, painful small fibre neuropathy, and transverse myelitis
      (independently or as part of neuromyelitis optica). We present the symptoms,
      signs, differential diagnoses, recommended diagnostic evaluation, and treatment
      of each of these, highlighting the features that should alert neurologists to
      consider Sjogren's syndrome.

PMID- 24307006
TI  - Transcatheter valve-in-ring implantation after a failed surgical mitral repair
      using a transseptal approach and a veno-arterial loop for valve placement.
AB  - A failure of a mitral valve repair, which includes the implantation of a mitral
      annuloplasty ring in the majority of cases, is associated with relevant
      mortality. Surgery is considered as the standard treatment for these patients.
      For patients who have an unacceptable high peri-surgical risk a transcatheter
      valve-in-ring (TVIR) procedure might be an option. Isolated case reports and
      small case series report on the feasibility of a TVIR implantation in mitral
      position. We present a case where a 29-mm Edwards Sapien valve was placed in a 32
      mm Carpentier Edwards ring. To our knowledge no valve has been implanted so far
      in this ring size and this is the first case where a veno-arterial loop was used
      as guide rail for valve implantation and helped considerably to position the
      valve properly.

PMID- 24307007
TI  - Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a
      real-life setting: results of the ETNA cohort.
AB  - Although the real-life benefits of bevacizumab may differ from clinical trials,
      observational data are rare. In this cohort study, the effectiveness of
      bevacizumab in first-line treatment of metastatic colorectal cancer was
      investigated. Patients initiating bevacizumab between January 2006 and December
      2007 were identified in 28 French centres. Outcomes were investigated in the
      whole cohort and in those with irinotecan-based treatment that was used in the
      pivotal clinical trial; patients were stratified using inclusion/exclusion
      criteria of the pivotal clinical trial (PCT) (eligible for the PCT, not eligible
      or unclassifiable). The Kaplan-Meier method estimated progression-free survival
      (PFS) and overall survival (OS). A total of 411 patients were included: 57 %
      male, median age 65.1 years, 78 % Eastern Cooperative Oncology Group performance
      status <=1, 88 % irinotecan-based regimen, median duration of bevacizumab use 5.5
      months, median OS = 25.3 months (95 % confidence interval, CI [23.3; 27.0]) and
      median PFS = 10.1 months (95 % CI [9.5; 11.0]). Among the 360 patients who
      received irinotecan-based chemotherapy, 144 would have been eligible for the PCT,
      194 not eligible and 22 unclassifiable. Median OS in those considered eligible
      was 29.1 (95 % CI [25.4; 33.6]) and in those considered not eligible this was
      24.9 months (95 % CI [21.3; 26.9]); median PFS was respectively 11.5 months (95 %
      CI [10.3; 12.0]) and 9.4 months (95 % CI [8.8; 10.3]). The effectiveness of
      bevacizumab was found to be similar to that found in other studies including
      clinical trials which is reassuring. 

PMID- 24307008
TI  - Young "healthy" smokers have functional and inflammatory changes in the nasal and
      the lower airways.
AB  - BACKGROUND: Smoking is responsible for most COPD. Although people with COPD often
      have concomitant nasal disease, there are few studies that report physiologic or
      inflammatory changes in the upper airways in young asymptomatic smokers. We
      investigated physiologic and inflammatory changes in the nasal and lower airways
      of young smokers and if these changes were related to smoking history. METHODS:
      Seventy-two subjects aged between 18 and 35 years (32 healthy nonsmokers and 40
      young smokers) participated in this study. We measured nasal mucociliary
      clearance (MCC), nasal mucus surface contact angle, cell counts, myeloperoxidase
      and cytokine concentrations in nasal lavage fluid, exhaled breath condensate
      (EBC) pH, and lung function. RESULTS: Smokers had faster MCC, an increased number
      of cells (macrophages, ciliated cells, and goblet cells), increased lavage
      myeloperoxidase concentration, and decreased EBC pH compared with nonsmokers.
      There was a significant inverse relationship between pack-year smoking history
      and EBC pH. There were no differences in lung function or mucus surface
      properties comparing smokers to nonsmokers. CONCLUSIONS: Young adult smokers have
      functional and inflammatory changes in the nasal and lower airways and these
      correlate with smoking history. However, in these young smokers, smoking history
      was not associated with pulmonary function decline, probably because it is
      unlikely that spirometry detects early physiologic changes in the airways. TRIAL
      REGISTRY: ClinicalTrials.gov; No.: NCT01877291; URL: www.clinicaltrials.gov.

PMID- 24307009
TI  - Merkel cell polyomavirus detection in Merkel cell cancer tumors in Northern
      Germany using PCR and protein expression.
AB  - Merkel cell carcinoma is a highly malignant skin cancer which predominantly
      occurs in elderly and immunocompromised persons. The identification of the Merkel
      cell polyomavirus (MCPyV) has inaugurated a new understanding of Merkel cell
      carcinoma pathogenesis. The frequent detection of the virus in Merkel cell
      carcinoma tissue (70-90%), its monoclonal integration in the tumor cells and the
      expression of viral oncogenes highly suggest that MCPyV is causally linked to the
      pathogenesis of the majority of Merkel cell cancer (MCC) cases. Using qualitative
      and quantitative PCR together with immunohistochemical staining this study aimed
      at characterizing the presence of MCPyV sequences and viral early gene expression
      in a cohort of MCC cases (n = 32) selected in Northern Germany. 40-57% of the
      cases were identified as MCPyV positive with 40.6% of the cases positive by
      immunohistochemical staining and 51.6-57.6% positive by PCR. Interestingly, in
      the majority (64%) of LT-Antigen positive tumors only 25-50% of tumor cells
      express LT-Antigen. These data are in accord with published studies describing
      heterogeneity in MCPyV viral loads and suggest that detection of MCPyV in Merkel
      cell carcinoma by PCR should be undertaken using multiple primer pairs.

PMID- 24307010
TI  - Double aortic arch without vascular ring: an unusual variation.

PMID- 24307013
TI  - Melting at high pressure: can first-principles computational chemistry challenge
      diamond-anvil cell experiments?

PMID- 24307014
TI  - A domino approach to dibenzopentafulvalenes by quadruple carbopalladation.

PMID- 24307015
TI  - Carbonylation of cyclotrisilenes.

PMID- 24307016
TI  - A di-substituted boron dication and its hydride-induced transformation to an NHC
      stabilized borabenzene.

PMID- 24307017
TI  - Hindered aryllithium reagents as partners in palladium-catalyzed cross-coupling:
      synthesis of tri- and tetra-ortho-substituted biaryls under ambient conditions.

PMID- 24307018
TI  - An adaptable and dynamically porous organic salt traps unique tetrahalide
      dianions.

PMID- 24307019
TI  - Metal-free OLED triplet emitters by side-stepping Kasha's rule.

PMID- 24307020
TI  - Proton cascade in a molecular solid: H/D exchange on mobile and immobile water.

PMID- 24307021
TI  - Memories of cricket, Guinness and green gels.

PMID- 24307022
TI  - Thirty years of fun with antenna pigment-proteins and photochemical reaction
      centers: A tribute to the people who have influenced my career.
AB  - The author summarizes the research contributions to photosynthesis made by him,
      his graduate and postdoctoral students, visiting scientists and by his
      collaboration with other photosynthesis workers during 1964-1994. The development
      of isolation procedures and biochemical/biophysical characterization of antenna
      pigment-proteins and photochemical reaction centers are described together with
      the author's education and experiences as a scientific researcher. Some anecdotes
      hopefully add insight into what it was like to be in this area of science during
      the period. 

PMID- 24307024
TI  - Characterization of a Synechococcus sp. strain PCC 7002 mutant lacking
      Photosystem I. Protein assembly and energy distribution in the absence of the
      Photosystem I reaction center core complex.
AB  - A Synechococcus sp. strain PCC 7002 DeltapsaAB::cat mutant has been constructed
      by deletional interposon mutagenesis of the psaA and psaB genes through selection
      and segregation under low-light conditions. This strain can grow
      photoheterotrophically with glycerol as carbon source with a doubling time of 25
      h at low light intensity (10 MUE m(-2) s(-1)). No Photosystem I (PS I)-associated
      chlorophyll fluorescence emission peak was detected in the DeltapsaAB::cat
      mutant. The chlorophyll content of the DeltapsaAB::cat mutant was approximately
      20% that of the wild-type strain on a per cell basis. In the absence of the PsaA
      and PsaB proteins, several other PS I proteins do not accumulate to normal
      levels. Assembly of the peripheral PS I proteins PsaC,PsaD, PsaE, and PsaL is
      dependent on the presence of the PsaA and PsaB heterodimer core. The precursor
      form of PsaF may be inserted into the thylakoid membrane but is not processed to
      its mature form in the absence of PsaA and PsaB. The absence of PS I reaction
      centers has no apparent effect on Photosystem II (PS II) assembly and activity.
      Although the mutant exhibited somewhat greater fluorescence emission from
      phycocyanin, most of the light energy absorbed by phycobilisomes was efficiently
      transferred to the PS II reaction centers in the absence of the PS I. No light
      state transition could be detected in the DeltapsaAB::cat strain; in the absence
      of PS I, cells remain in state 1. Development of this relatively light-tolerant
      strain lacking PS I provides an important new tool for the genetic manipulation
      of PS I and further demonstrates the utility of Synechococcus sp. PCC 7002 for
      structural and functional analyses of the PS I reaction center. 

PMID- 24307025
TI  - Reaction centers of Rhodobacter sphaeroides R26 containing C-3 acetyl and vinyl
      (bacterio)pheophytins at sites HA,B.
AB  - The native bacteriopheophytin a in reaction centers of Rb. sphaeroides R26 has
      been exchanged with modified bacteriopheophytins (bacteriochlorins), as well as
      with plant-type pheophytins (chlorins). Emphasis is on four pigments, which
      differ by their C-3 substituents (vinyl or acetyl) or their state of oxidation
      (chlorin or bacteriochlorin). The native BPhe a, which is a member of this group,
      can be replaced by the other three at both binding sites, HA and HB. However,
      exchange at HB proceeds more readily. Optical spectra (absorption, cd) show
      characteristic shifts, and the cd spectra indicate induced interactions between
      HA,B and BA,B and possibly also with P. Upon flash illumination, all modified
      reaction centers show reversible electron transfer to QB with recombination times
      comparable to native reaction centers. Forward rates and electron-transfer yields
      are also reported for some of the pigments. 

PMID- 24307023
TI  - Function and organization of Photosystem I polypeptides.
AB  - Photosystem I functions as a plastocyanin:ferredoxin oxidoreductase in the
      thylakoid membranes of chloroplasts and cyanobacteria. The PS I complex contains
      the photosynthetic pigments, the reaction center P700, and five electron transfer
      centers (A0, A1, FX, FA, and FB) that are bound to the PsaA, PsaB, and PsaC
      proteins. In addition, PS I complex contains at least eight other polypeptides
      that are accessory in their functions. Recent use of cyanobacterial molecular
      genetics has revealed functions of the accessory subunits of PS I. Site-directed
      mutagenesis is now being used to explore structure-function relations in PS I.
      The overall architecture of PSI complex has been revealed by X-ray
      crystallography, electron microscopy, and biochemical methods. The information
      obtained by different techniques can be used to propose a model for the
      organization of PS I. Spectroscopic and molecular genetic techniques have
      deciphered interaction of PS I proteins with the soluble electron transfer
      partners. This review focuses on the recent structural, biochemical and molecular
      genetic studies that decipher topology and functions of PS I proteins, and their
      interactions with soluble electron carriers. 

PMID- 24307026
TI  - Effect of Photosystem II inhibitor K-15 on photochemical reactions of the
      isolated D1/D2 cytochrome b559 complex.
AB  - Effect of a highly efficient inhibitor of Photosystem II (PS II), K-15 (4
      [methoxy-bis-(trifluoromethyl)methyl)-2,6-dinitrophenyl hydrazone methyl ketone),
      was investigated using the D1/D2/cytochrome b559 reaction centre (RC) complex. A
      novel approach for photoaccumulating reduced pheophytin (Pheo(-)) in the absence
      of the strong reducing agent, sodium dithionite, was demonstrated which involved
      illumination in the presence of TMPD (from 5 to 100 MUM) under anaerobic
      conditions. The addition of K-15 at concentrations of 0.5 MUM and 2 MUM resulted
      in approx. 50% and near 100%, respectively, inhibition of this photoreaction,
      while subsequent additions of dithionite eliminated the inhibitory effect of K
      15. Methyl viologen induced similar inhibition at much higher concentrations (>1
      mM). Moreover, K-15 efficiently quenched the 'variable' part of chlorophyll
      fluorescence (which is the recombination luminescence of the pair P680 (+) Pheo(
      )). A 50% inhibition was induced by 5 MUM K-15 and the effect was maximal in the
      range 20 to 200 MUM. Photooxidation of P680 in the presence of 0.1 mM
      silicomolybdate was also efficiently inhibited by K-15 (50% inhibition at 15
      MUM). The data are consistent with the idea put forward earlier (Klimov et al.
      1992) that the inhibitory effect of K-15 is based on facilitating a rapid
      recombination between Pheo(-) and P680 (+) (or Z(+)) via its redox properties.
      The inhibitor can be useful for suppressing PS II reactions in isolated RCs of PS
      II which are resistant to all traditional inhibitors, like diuron, and probably
      functions by substituting for QA missing in the preparation.At a concentration of
      0.5-50 MUM K-15 considerably increased both the rate and extent of cytochrome
      b559 photoreduction in the presence, as well as in the absence, of 5 mM MnCl2.
      Consequently it is suggested that K-15 also serves as a mediator for electron
      transfer from Pheo(-) to cytochrome b559. 

PMID- 24307027
TI  - Isolation and initial characterization of virescent mutants of Arabidopsis
      thaliana.
AB  - In higher plants, development of the chloroplasts must be coordinated with
      development of the leaf. In order to study the signals that synchronize these two
      developmental processes, we have isolated virescent (delayed in greening) mutants
      of Arabidopsis thaliana. Two such mutants that have pale-green young leaves which
      gradually green more fully during leaf maturation have been partially
      characterized. The two, vir1 and vir2, are due to separate nuclear recessive
      mutations. The pale leaves of vir1 and vir2 both had reduced 77 degrees K
      fluorescence emission at 730-734 nm relative to that at 686-687 nm, indicating a
      reduction in the relative amount of LHC I compared to WT. As leaves greened, the
      amount of LHC I increased to near wildtype levels. The shift in the fluorescence
      emission peak from 730 nm to 734 nm, characteristic of maturing LHC I, was seen
      for vir1, but not vir2, suggesting that vir1 is a regulatory mutant while vir2
      may be defective in a specific aspect(s) of LHC I function. 

PMID- 24307028
TI  - Consequences of LHC II deficiency for photosynthetic regulation in chlorina
      mutants of barley.
AB  - The light-harvesting chlorophyll a/b proteins associated with PS II (LHC II) are
      often considered to have a regulatory role in photosynthesis. The photosynthetic
      responses of four chlorina mutants of barley, which are deficient in LHC II to
      varying degrees, are examined to evaluate whether LHC II plays a regulatory role
      in photosynthesis. The efficiencies of light use for PS I and PS II
      photochemistry and for CO2 assimilation in leaves of the mutants were monitored
      simultaneously over a wide range of photon flux densities of white light in the
      presence and absence of supplementary red light. It is demonstrated that the
      depletions of LHC II in these mutants results in a severe imbalance in the
      relative rates of excitation of PS I and PS II in favour of PS I, which cannot be
      alleviated by preferential excitation of PS II. Analyses of xanthophyll cycle
      pigments and fluorescence quenching in leaves of the mutants indicated that the
      major LHC II components are not required to facilitate the light-induced
      quenching associated with zeaxanthin formation. It is concluded that LHC II is
      important to balance the distribution of excitation energy between PS I and PS II
      populations over a wide range of photon flux densities. It appears that LHC II
      may also be important in determining the quantum efficiency of PS II
      photochemistry by reducing the rate of quenching of excitation energy in the PS
      II primary antennae. 

PMID- 24307029
TI  - Circadian expression of the light-harvesting protein of Photosystem II in
      etiolated bean leaves following a single red light pulse: Coordination with the
      capacity of the plant to form chlorophyll and the thylakoid-bound protease.
AB  - The appearance of the light harvesting II (LHC II) protein in etiolated bean
      leaves, as monitored by immunodetection in LDS-solubilized leaf protein extracts,
      is under phytochrome control. A single red light pulse induces accumulation of
      the protein, in leaves kept in the dark thereafter, which follows circadian
      oscillations similar to those earlier found for Lhcb mRNA (Tavladoraki et al.
      (1989) Plant Physiol 90: 665-672). These oscillations are closely followed by
      oscillations in the capacity of the leaf to form Chlorophyll (Chl) in the light,
      suggesting that the synthesis of the LHC II protein and its chromophore are in
      close coordination. Experiments with levulinic acid showed that PChl(ide)
      resynthesis does not affect the LHC II level nor its oscillations, but new Chl a
      synthesis affects LHC II stabilization in thylakoids, implicating a proteolytic
      mechanism. A proteolytic activity against exogenously added LHC II was detected
      in thylakoids of etiolated bean leaves, which was enhanced by the light pulse.
      The activity, also under phytochrome control, was found to follow circadian
      oscillations in verse to those in the stabilization of LHC II protein in
      thylakoids. Such a proteolytic mechanism therefore, may account for the circadian
      changes observed in LHC II protein level, being implicated in pigment-protein
      complex assembly/stabilization during thylakoid biogenesis. 

PMID- 24307030
TI  - Assessing modulation of stromal and thylakoid light-harvesting complex-II
      phosphatase activities with phosphopeptide substrates.
AB  - The study of the light-harvesting complex II (LHC-II) phosphatase activity has
      been difficult due to the membrane association of its substrate. Thylakoid
      membranes labeled with [gamma-(32)P]ATP were incubated with chymotrypsin,
      releasing phosphopeptides which served as labeled substrates for LHC-II
      phosphatase. Utilizing these phosphopeptides as substrates, protein phosphatase
      activities have been identified in both the thylakoid membrane and the stromal
      fraction. The thylakoid-bound phosphatase was liberated from the membrane with a
      sub-solubilizing concentration of Brij 35. The membrane and the stromal protein
      phosphatases were inhibited by NaF and EDTA, but not inhibited by microcystin-LR.
      The stromal phosphatase differed from the membrane phosphatase in pH optimum, in
      its lack of inhibition by molybdate ions, and by its response to magnesium and
      manganese ions. Using the soluble chymotryptic peptide substrate, the effect of
      light on pea thylakoid-bound LHC-II phosphatase activity was also assessed.
      Incubation of the thylakoid membranes in the light caused a 35% inhibition of LHC
      II phosphatase activity. The inhibition was diminished by the addition of DCMU.
      Addition of 10 mM dithiothreitol stimulated the activity in darkness and obviated
      the inhibition when exposed to light. These studies suggest that positive or
      negative regulation of the LHC-II phosphatase activity is possible in vivo. 

PMID- 24307031
TI  - Energy transfer for low temperature fluorescence in PS II mutant thylakoids.
AB  - The Chl-protein complexes of three maize (Zea mays L.) mutants and one barley
      (Hordeum vulgare L.) mutant were analyzed using low temperature Chl fluorescence
      emissions spectroscopy and LDS-polyacrylamide gel electrophoresis. The maize
      mutants hcf-3, hcf-19, and hcf-114 all exhibited a high Chl fluorescence (hcf)
      phenotype indicating a disruption of the energy transfer within the
      photosynthetic apparatus. The mutations in each of these maize mutants affects
      Photosystem II. The barley mutant analyzed was the well characterized Chl b-less
      mutant chlorina-f2, which did not exhibit the hcf phenotype. Chlorina-f2 was used
      because no complete Chl b-less mutant of maize is available. Analysis of hcf-3,
      hcf-19, and hcf-114 revealed that in the absence of CP43, LHC II can still
      transfer excitation energy to CP47. These results suggest that in mutant
      membranes LHC II can interact with CP47 as well as CP43. This functional
      interaction of LHC II with CP47 may only occur in the absence of CP43, however,
      it is possible that LHC II is positioned in the thylakoid membranes in a manner
      which allows association with both CP43 and CP47. 

PMID- 24307032
TI  - Isolation of membrane bound light-harvesting-complexes from the dinoflagellates
      Heterocapsa pygmaea and Prorocentrum minimum.
AB  - We have isolated Chl a-Chl c-carotenoid binding proteins from the dinoflagellates
      Prorocentrum minimum and Heterocapsa pygmaea grown under high (500 MUmol m(-2) s(
      1), HL) and low (35 MUmol m(-2) s(-1), LL) light conditions. We compared various
      isolation procedures of membrane bound light harvesting complexes (LHCs) and
      assayed the functionality of the solubilized proteins by determining the energy
      transfer efficiency from the accessory pigments to Chl a by means of fluorescence
      excitation spectra. The identity of the newly isolated protein-complexes were
      confirmed by immunological cross-reactions with antibodies raised against the
      previously described membrane bound Chl a-c proteins (Boczar et al. (1980) FEBS
      Lett 120: 243-247). Spectroscopic analysis demonstrated the relatedness of these
      proteins with the recently described Chl-a-c 2-peridinin (ACP) binding protein
      (Hiller et al. (1993) Photochem Photobiol 57: 125-131; Iglesias Prieto et al.
      (1993) Phil Trans R Soc London B 338: 381-392). The water-soluble peridinin-Chl a
      binding-protein (PCP) was not detectable in P. minimum. Two functional forms of
      ACP with different pigmentation were isolated. A variant of ACP which was
      isolated from high-light grown cells, that specifically binds increased amounts
      of diadinoxanthin was compared to the previously described ACPs that bind
      proportionately more peridinin. 

PMID- 24307033
TI  - Sequence conservation of light-harvesting and stress-response proteins in
      relation to the three-dimensional molecular structure of LHCII.
AB  - The structure of pea light-harvesting complex LHCII determined to 3.4 A
      resolution by electron crystallography (Kuhlbrandt, Wang and Fujiyoshi (1994)
      Nature 367: 614-621) was examined to determine the relationship between
      structural elements and sequence motifs conserved in the extended family of light
      harvesting antennas (Chl a/b, fucoxanthin Chl a/c proteins) and membrane
      intrinsic stress-induced proteins (ELIPs) to which LHCII belongs. It is predicted
      that the eukaryotic ELIPs can bind at least four molecules of Chl. The one-helix
      prokaryotic ELIP of Synechococcus was modelled as a homodimer based on the high
      degree of conservation of residues involved in the interactions of the first (B)
      and third (A) helices of LHCII. 

PMID- 24307034
TI  - Studies on the light-harvesting complexes from the thermotolerant purple
      bacterium Rhodopseudomonas cryptolactis.
AB  - The antenna complexes from Rps. cryptolactis have been isolated and purified.
      Rps. cryptolactis contains two types of variable antenna complex, B800-850 and
      B800-820 as well as the 'core' B875 antenna complex. The variable antenna
      complexes contain more than two types of antenna apoprotein, and have a
      Bchla:carotenoid ratio of ~2:1. They can both be crystallised, but the B800-820
      complex is the easiest with which to get relatively large single 3-D crystals (up
      to 0.5 mm in each dimension). 

PMID- 24307035
TI  - The carboxyl-terminal region of the spinach PsaD subunit contains information for
      its specific assembly into plant thylakoids.
AB  - The assembly of the multi-subunit membrane-protein Photosystem I (PS I) complex
      involves incorporation of peripheral proteins into the complex. Here we studied
      assembly of the PsaD subunit of the cyanobacterial and plant PS I into the
      thylakoid membranes. We generated partial and chimeric psaD genes from which
      labeled proteins were synthesized in vitro. Assembly of these proteins into the
      cyanobacterial or plant thylakoids was assayed. The deletion of leader sequence
      and N-terminal extension of spinach prePsaD did not inhibit its assembly into
      spinach or cyanobacterial thylakoids. Addition of these sequences to the
      cyanobacterial PsaD did not enable it to assemble into plant thylakoids.
      Moreover, these additions significantly decreased the ability of the chimeric
      proteins to assemble into cyanobacterial thylakoids. In contrast, when the
      carboxyl-terminal half of cyanobacterial PsaD was replaced by the corresponding
      region of the spinach PsaD, the chimeric protein could assemble into both spinach
      and cyanobacterial thylakoids. Therefore, information in the carboxyl-terminal
      region of spinach PsaD is crucial for its assembly into plant thylakoids. 

PMID- 24307037
TI  - Light-induced biogenesis of the light-harvesting complexes of Photosystems I and
      II : Gene expression and protein accumulation.
AB  - The light-harvesting complexes of Photosystems I and II contain multiple
      chlorophyll-carotenoid-binding proteins. The stoichiometry and topology of the
      LHCs is precisely defined to optimally funnel captured light energy to the
      reaction center. The manner in which this exact arrangement is accomplished is
      not known. As an initial means to understand the mechanisms involved in
      establishing a functional LHC, the influence of light on LHC gene expression and
      protein accumulation was studied during the light-induced greening of etiolated
      wild type and chlorophyll b-less mutant barley seedlings. Light, involving
      phytochrome, promotes the expression of all LHC genes with the same relative
      kinetics. LHC protein accumulation closely parallels the increases observed in
      transcript levels. Differential accumulation of LHC transcripts or protein was
      not evident in wild type seedlings. Post-translational factors are likely to be
      involved in fine tuning the position and stoichiometry of the individual LHCs
      around the reaction center. 

PMID- 24307036
TI  - Assembly of the chlorophyll-protein complexes.
AB  - The biogenesis of photosynthetic complexes in plants and algae is a multi-step
      process that involves intricate coordination of steps in two intracellular
      compartments, the chloroplast and the cytoplasm. The process initiates with the
      transcription and translation of the various polypeptide subunits. The nuclear
      encoded Chl-binding proteins are translated on cytoplasmic ribosomes as
      precursors that have a transit (leader) sequence at their amino-terminus. The
      precursors are post-translationally imported into the chloroplasts,
      proteolytically processed into their mature forms, inserted into the
      thylationally imported into the chloroplasts, proteolytically processed into
      their mature forms, inserted into the thylakoid membrane, and bound to their co
      factors (and pigments) and with other subunits to form an active complex. The
      order and mechanisms by which these events occur, are currently being discovered.
      Electrostatic interactions, the 'positive inside rule', interhelix interactions,
      interactions with lipids and chaperone proteins affect the insertion and
      stabilization of the Chl-proteins in the thylakoids. This review describes the
      events occurring during the integration and organization of the Chl-proteins. 

PMID- 24307039
TI  - Structural and functional properties of the coleoptile chloroplast:
      Photosynthesis and photosensory transduction.
AB  - Recent studies have shown that guard cell and coleoptile chloroplasts appear to
      be involved in blue light photoreception during blue light-dependent stomatal
      opening and phototropic bending. The guard cell chloroplast has been studied in
      detail but the coleoptile chloroplast is poorly understood. The present study was
      aimed at the characterization of the corn coleoptile chloroplast, and its
      comparison with mesophyll and guard cell chloroplasts. Coleoptile chloroplasts
      operated the xanthophyll cycle, and their zeaxanthin content tracked incident
      rates of solar radiation throughout the day. Zeaxanthin formation was very
      sensitive to low incident fluence rates, and saturated at around 800-1000 MUmol
      m(-2) s(-1). Zeaxanthin formation in corn mesophyll chloroplasts was insensitive
      to low fluence rates and saturated at around 1800 MUmol m(-2) s(-1). Quenching
      rates of chlorophyll a fluorescence transients from coleoptile chloroplasts
      induced by saturating fluence rates of actinic red light increased as a function
      of zeaxanthin content. This implies that zeaxanthin plays a photoprotective role
      in the coleoptile chloroplast. Addition of low fluence rates of blue light to
      saturating red light also increased quenching rates in a zeaxanthin-dependent
      fashion. This blue light response of the coleoptile chloroplast is analogous to
      that of the guard cell chloroplast, and implicates these organelles in the
      sensory transduction of blue light. On a chlorophyll basis, coleoptile
      chloroplasts had high rates of photosynthetic oxygen evolution and low rates of
      photosynthetic carbon fixation, as compared with mesophyll chloroplasts. In
      contrast with the uniform chloroplast distribution in the leaf, coleoptile
      chloroplasts were predominately found in the outer cell layers of the coleoptile
      cortex, and had large starch grains and a moderate amount of stacked grana and
      stroma lamellae. Several key properties of the coleoptile chloroplast were
      different from those of mesophyll chloroplasts and resembled those of guard cell
      chloroplasts. We propose that the common properties of guard cell and coleoptile
      chloroplasts define a functional pattern characteristic of chloroplasts
      specialized in photosensory transduction. 

PMID- 24307038
TI  - Genetic engineering of thylakoid protein complexes by chloroplast transformation
      in Chlamydomonas reinhardtii.
AB  - Chloroplast transformation of Chlamydomonas reinhardtii has developed into a
      powerful tool for studying the structure, function and assembly of thylakoid
      protein complexes in a eukaryotic organism. In this article we review the
      progress that is being made in the development of procedures for efficient
      chloroplast transformation. This focuses on the development of selectable markers
      and the use of Chlamydomonas mutants, individually lacking thylakoid protein
      complexes, as recipients. Chloroplast transformation has now been used to
      engineer all four major thylakoid protein complexes, photosystem II, photosystem
      I, cytochrome b 6/f and ATP synthase. These results are discussed with an
      emphasis on new insights into assembly and function of these complexes in
      chloroplasts as compared with their prokaryotic counterparts. 

PMID- 24307040
TI  - The impact of work-limiting disability on labor force participation.
AB  - According to the justification hypothesis, non-employed individuals may over
      report their level of work limitation, leading to biased census/survey estimates
      of the prevalence of severe disabilities and the associated labor force
      participation rate. For researchers studying policies which impact the disabled
      or elderly (e.g., Supplemental Security Income, Disability Insurance, and Early
      Retirement), this could lead to significant bias in key parameters of interest.
      Using the American Community Survey, we examine the potential for both inflated
      and deflated reported disability status and generate a general index of
      disability, which can be used to reduce the bias of these self-reports in other
      studies. We find that at least 4.8 million individuals have left the labor force
      because of a work-limiting disability, at least four times greater than the
      impact implied by our replication of previous models.

PMID- 24307041
TI  - Editors' note.

PMID- 24307042
TI  - Chemical ecology of marine organisms: An overview.
AB  - An overview of marine chemical ecology is presented. Emphasis is placed on
      antipredation, invertebrate-toxic host relationships, antifouling, competition
      for space, species dominance, and the chemistry of ecological interactions. 

PMID- 24307043
TI  - Chemically stimulated feeding behavior in marine animals : Importance of chemical
      mixtures and involvement of mixture interactions.
AB  - A review is provided of the chemical components in tissue extracts that elicit
      feeding behavior in marine fish and crustaceans. For most species, the major
      stimulants of feeding behavior in excitatory extracts are an assemblage of common
      metabolites of low molecular weight including amino acids, quaternary ammonium
      compounds, nucleosides and nucleotides, and organic acids. It is often mixtures
      of substances rather than individual components that account for the stimulatory
      capacity of a natural extract. Recent studies using a shrimp,Palaemonetes pugio,
      are described in which behavioral bioassays were conducted with complex synthetic
      mixtures formulated on the basis of the composition of four tissue extracts.
      These results indicate that synergistic interactions occur among the mixture
      components. The neural mechanisms whereby marine crustaceans receive and code
      information about chemical mixtures are also reviewed. Narrowly tuned receptor
      cells, excited only by particular components of food extracts such as specific
      amino acids, nucleotides, quaternary ammonium compounds, and ammonium ions, are
      common in lobsters and could transmit information about mixtures as a labeled
      line code. However, since physiological recordings indicate that most higher
      level neurons in the brain each transmit information about many components of
      mixtures, rather than about a single component, it is suggested that information
      about a complex food odor is transmitted as an across-fiber pattern, instead of a
      labeled-line code. Electrophysiological recordings of responses of peripheral and
      central neurons of lobsters to odor mixtures and their components reveal that
      suppressive interactions occur, rather than the synergistic interactions noted
      earlier in the behavioral studies. Possible reasons for these differences are
      discussed. Evidence from the behavioral study indicates that the "direction" of a
      mixture interaction can be concentration-dependent and the synergism may occur at
      low mixture concentrations, while suppression may occur at high concentrations. 

PMID- 24307044
TI  - Macromolecular cues in marine systems.
AB  - A review of the roles of biopolymers as marine chemical cues is presented. The
      goal of the review is to provide a context within which to view present research
      and to provide insight into future research potential for macromolecules in
      marine chemical ecology. The roles of peptides, proteins, glycoproteins,
      proteoglycans, lectins, and mucopolysaccharides are discussed. Biological events
      mediated include: larval settlement and metamorphosis, gamete attraction,
      predator-prey interactions, alarm responses, feeding responses, nonfood resource
      acquisition, trail following, and larval-release behavior. Molecular origins,
      transmission, modulation, and multifunctionality of cues are discussed and
      illustrated with specific examples. The advantages of biopolymers, especially
      peptides and proteins, as specific cues in marine systems derive from their
      solubility, specific information content (due to the asymmetric nature of the
      monomer and the wordlike information content of the primary structure of the
      polymer), distance transmission in water by bulk flow rather than diffusion,
      relatively high signal-to-noise ratio, and common occurrence as structural and
      metabolic components of all living organisms. 

PMID- 24307045
TI  - Plant and fungal cell wall fragments activate expression of proteinase inhibitor
      genes for plant defense.
AB  - Plant and fungal cell wall fragments produced by enzymic degradation during pest
      attacks are hypothesized to be activators of a universal recognition system for
      locally and systemically activating genes which control the synthesis of plant
      defense chemicals such as the antibiotic phytoalexins and antinutritive
      proteinase inhibitors. Proteinase inhibitor cDNAs have been prepared from wound
      induced mRNAs, isolated, and characterized. The cDNAs have been utilized to
      quantify specific proteinase inhibitor mRNAs in leaves following wounding or
      simulated insect attacks. The cDNAs have also been utilized as hybridization
      probes to isolate and characterize proteinase inhibitor genes from tomato and
      potato genomic DNA. Proteinase inhibitor proteins have been induced in tomato
      leaves by chewing insects and shown to be highly correlated with a systemically
      mediated reduction in the nutritional quality of the leaves toward the larval
      noctuidSpodoptera exigua. Thus, the wound-induced proteinase inhibitors, whose
      genes in tomato leaves can be activated by wounding, insect attacks, and plant
      and fungal cell wall fragments, can significantly decrease the quality of the
      leaves for such herbivorous insects. This inducible set of biochemical reactions
      leading to the de novo biosynthesis of proteinase inhibitors is, therefore,
      considered to be a potentially important defense of plant leaves that should be
      considered both in developing general theories on insect-plant interactions and
      in selecting insect-resistant crop varieties. 

PMID- 24307046
TI  - Coadaptation ofDrosophila and yeasts in their natural habitat.
AB  - The mutualistic interactions of cactophilicDrosophila and their associated yeasts
      in the Sonoran Desert are studied as a system which has evolved within the
      framework of their host cactus stem chemistry. Because theDrosophila-yeast system
      is saphrophytic, their responses are not thought to directly influence the
      evolution of the host. Host cactus stem chemistry appears to play an important
      role in determining where cactophilicDrosophila breed and feed. Several chemicals
      have been identified as being important. These include sterols and alkaloids of
      senita as well as fatty acids and sterol diols of agria and organpipe cactus.
      Cactus chemistry appears to have a limited role in directly determining the
      distribution of cactus-specific yeasts. Those effects which are known are due to
      unusual lipids of organpipe cactus and triterpene glycosides of agria and
      organpipe cactus.Drosophilayeast interactions are viewed as mutualistic and can
      take the form of (1) benefits to theDrosophila by either direct nutritional gains
      or by detoxification of harmful chemicals produced during decay of the host stem
      tissue and (2) benefits to the yeast in the form of increased likelihood of
      transmission to new habitats. Experiments on yeast-yeast interactions in decaying
      agria cactus provide evidence that the yeast community is coadapted. This
      coadaptation among yeasts occurs in two manners: (1) mutualistic increases in
      growth rates (which are independent of the presence ofDrosophila larvae) and (2)
      stabilizing competitive interactions when growth reaches carrying capacity. This
      latter form is dependent on larval activity and results in benefits to the larvae
      present. In this sense, the coadapted yeast community is probably also coadapted
      with respect to itsDrosophila vector. 

PMID- 24307047
TI  - Cellulose digestion inMonochamus marmorator Kby. (Coleoptera: Cerambycidae): Role
      of acquired fungal enzymes.
AB  - Larvae of the balsam fir sawyer,Monochamus marmorator Kby. (Coleoptera,
      Cerambycidae), contain midgut digestive enzymes active against hemicellulose and
      cellulose. Cellulases from larvae fed on balsam fir wood infected with the
      fungus,Trichoderma harzianum Rifai (Deuteromycetes, Moniliales, Moniliaceae),
      were found to be identical to those of the cellulase complex produced by this
      fungus when compared using chromatography, electrophoresis, and isofocusing. When
      larvae are maintained on a fungus-free diet, their midgut fluids lack
      cellulolytic activity, and they are unable to digest cellulose. Cellulolytic
      capacity can be restored by feeding the larvae wood permeated by fungi. We
      conclude that the enzymes which enableM. marmorator larvae to digest cellulose
      are not produced by the larvae. Instead, the larvae acquire the capacity to
      digest cellulose by ingesting active fungal cellulases while feeding in fungus
      infected wood. 

PMID- 24307049
TI  - Chemically mediated behavior in Acari: Adapations for finding hosts and mates.
AB  - Ticks and mites respond to a limited spectrum of stimuli in their search for
      hosts and mates. Airborne chemical signals include carbon dioxide, ammonia,
      organic acids, terpenoids, 2,6-dichlorophenol, and other phenolic compounds.
      These are detected primarily by sensilla in and adjacent to Haller's organ. Most
      ixodid species examined have one or more multiporose sensilla that detect such
      volatiles. These olfactoreceptors enable the ticks to respond to remote volatile
      chemicals from hosts and from the other ticks, e.g., sex pheromones. Other
      sensilla, probably mechanogustatory in function, also occur on the tarsi.
      Gustatory sensilla on the palps detect assembly pheromones that enable ticks and
      mites to respond to conspecific or heterospecific chemical stimuli in their
      environment. Responses to those stimuli in ticks result in clustering, i.e.,
      arrestant behavior. Arrestant behavior also occurs in certain mites. Finally,
      cheliceral chemosensilla enable ticks to recognize specific phagostimulants in
      host blood, e.g., ATP and glutathione, that stimulate feeding. InDennacentor
      variabilis andD. andersoni, these same cheliceral chemosensilla recognize species
      specific genital sex pheromones in the vulvae of conspecific mates, without which
      they do not copulate. 

PMID- 24307048
TI  - Behavioral responses to chemical cues by bacteria.
AB  - Bacterial chemotaxis presents a model sensory system in which cells modulate the
      direction of rotation of their flagella in response to gradients of certain
      chemicals. The chemotactic machinery ofEscherichia coli is currently being
      systematically reduced to its individual components through the accomplishments
      of behavioral, physical, genetic, molecular genetic, and biochemical analyses.
      Thirteen of the so called "MCP-related" class of chemotaxis gene products are
      known. Transmembrane methyl-accepting chemotaxis proteins (MCPs) are important
      for the chemical sensing, signal generation, and sensory adaptation processes.
      Soluble chemotaxis proteins relay information from these MCPs to structural
      components of the flagella referred to as switch proteins. Emphasis here is on
      the separate roles each of these groups of chemotaxis proteins perform, as well
      as their protein-protein relationships. 

PMID- 24307050
TI  - Coevolutionary adaptations of rootworm beetles (Coleoptera: Chrysomelidae) to
      cucurbitacins.
AB  - The cucurbitacins are oxygenated tetracyclic triterpenoids produced as secondary
      plant compounds by nearly all genera of Cucurbitaceae. The very bitter and toxic
      cucurbitacins are effective semiochemicals acting ecologically as allomones to
      protect the Cucurbitaceae from attack by a variety of invertebrate and vertebrate
      herbivores. For the Luperini (Coleoptera: Chrysomelidae: Galerucinae) the
      cucurbitacins have become kairomones for host selection, affecting the behavior
      of this large group of 1500 species of Aulacophorina (Old World) and Diabroticina
      (New World) by arrest and compulsive feeding. When feeding on bitter cucurbits
      these beetles sequester large amounts of cucurbitacins in their blood and
      tissues, and these act as allomones to deter predation. Specific detoxification
      and excretory mechanisms of the Diabroticina enable these beetles to avoid the
      toxic effects of the cucurbitacins. 

PMID- 24307051
TI  - Phytochemical basis of learning inRhagoletis pomonella and other herbivorous
      insects.
AB  - Examples of phytochemically-based learning of host preference in herbivorous
      insects are reviewed in the context of traditionally important issues: the number
      and kinds of chemicals involved; which sensory modalities are affected; whether
      peripheral or central nervous processing is altered; and whether learning is
      associative or not. A fifth issue addressed here- whether experience enhances a
      feeding or ovipositing insect's propensity to accept familiar chemical stimuli or
      to reject novel chemical stimuli-has been ignored in previous studies. Following
      the review, evidence is presented indicating that female apple maggot flies
      (Ragoletis pomonella) learn to reject both novel physical and novel chemical
      stimuli. 

PMID- 24307052
TI  - Biochemical insight into insecticidal properties ofL-Canavanine, a higher plant
      protective allelochemical.
AB  - L-Canavanine manifests potent insecticidal properties in a canavanine-sensitive
      insect such as the tobacco hornworm,Manduca sexta (L.) (Sphingidae).
      Investigations of the biochemical basis for the antimetabolic properties of this
      arginine analog reveal that it is activated and aminoacylated by arginyl tRNA
      synthetase and incorporated into the nascent polypeptide chain. This creates
      structurally aberrant, canavanine-containing proteins that can possess altered
      physicochemical properties. Evidence is presented in studies with the tobacco
      hornworm; the canavanine-adapted bruchid beetle,Caryedes brasiliensis (Bruchidae)
      and the weevil,Sternechus tuberculatus (Curculionidae); as well as the canavanine
      resistant larvae ofHeliothis virescens [Noctuidae] to support the contention that
      formation of aberrant, canavanyl proteins produce deleterious biological effects
      and is a significant basis for canavanine's antimetabolic properties. 

PMID- 24307053
TI  - Cardenolide connection between overwintering monarch butterflies from Mexico and
      their larval food plant,Asclepias syriaca.
AB  - The majority (85%) of 394 monarch butterflies sampled from overwintering sites in
      Mexico contain the same epoxy cardenolide glycosides, including most
      conspicuously a novel polar glycoside with a single genin-sugar bridge
      (aspecioside), as occur in the milkweedsAsclepias speciosa andA. syriaca. This
      cardenolide commonality was established by isolating aspecioside and syriobioside
      from the wings of overwintering monarchs and the two plant species, and comparing
      Chromatographie and NMR spectrometric characteristics of the isolates. When
      combined with the migratory pattern of monarchs and the distribution of these two
      milkweed species, this chemical evidence lends strong support to the hypothesis
      thatA. syriaca is the major late summer food plant of monarchs in eastern North
      America. This finding may be of ecological importance, forA. syriaca contributes
      less cardenolide and cardenolides of lower emetic potency to monarchs than most
      milkweeds studied to date. 

PMID- 24307054
TI  - Sequestration of cardenolides inOncopeltus fasciatus: Morphological and
      physiological adaptations.
AB  - The morphological and physiological adaptations associated with sequestration of
      cardenolides by the lygaeidOncopeltus fasciatus are summarized and discussed.
      Cardenolides are efficiently accumulated inO. fasciatus; however, the insect does
      not appear to suffer any physiological cost as a result of handling large amounts
      of these plant toxins. Morphological adaptations of the insect include a modified
      integument composed of a double layered epidermis with an inner layer (the
      dorsolateral space) specialized for cardenolide storage. Special weak areas of
      the cuticle are found on both the thorax and abdomen, which rupture when the
      insect is squeezed, resulting in the cardenolide-rich contents of the inner
      epidermal layer being released onto the body surface in the form of discrete
      spherical droplets. Physiological adaptations include selective sequestration of
      food plant cardenolides, concentration of cardenolides in the dorsolateral space,
      passive uptake of cardenolides at the gut and dorsolateral space requiring little
      energy output, reabsorption of secreted cardenolides by the Malpighian tubules,
      high in vivo tolerance to cardenolides, and the presence of cardenolide-resistant
      Na,K-ATPases. 

PMID- 24307055
TI  - Economics of chemical defense in chrysomelinae.
AB  - Chemical defense in chrysomelid larvae (subtribe Chrysomelina and Phyllodectina)
      is reviewed. Most species secrete autogenous monoterpenes. The diversity of their
      secretion is interpreted as a mechanism to reduce adaptation by predacious
      arthropods. The consequences of a host plant shift to the Salicacae are explored.
      Salicin from these host plants is used as a precursor for the salicylaldehyde
      secreted by the larvae of many species. This offers several advantages. It
      provides the larvae with an inexpensive and efficient defense. The recovery of
      the glucose moiety of the salicin contributes significantly to the larval energy
      budget. Adults sequester salicin in the eggs at concentrations which are toxic to
      ants. Owing to this maternal provisioning, neonate larvae produce salicylaldehyde
      from hatching onwards, whereas other species secreting monoterpenes are not
      protected at hatching. The secretion of salicylaldehyde by different species is
      considered to be chemical mimicry reinforcing visual aposematic signals. 

PMID- 24307056
TI  - US provider-reported diet and physical activity counseling to pregnant and non
      pregnant women of childbearing age during preventive care visits.
AB  - Healthy diet, physical activity and appropriate weight gain during pregnancy
      contribute to healthy birth outcomes. The Institute of Medicine recommends that
      women receive counseling about diet and exercise during preconception, pregnancy
      and postpartum periods. We sought to determine how often healthcare providers
      report counseling women of childbearing age about diet or exercise and if such
      rates vary by pregnancy, overweight/obesity status or physician specialty. We
      combined the 2005-2010 National Ambulatory Medical Care Survey and the National
      Hospital Ambulatory Medical Care Survey to obtain nationally representative
      estimates of outpatient preventive care visits for women of child-bearing age (15
      44 years). Accounting for survey design, we compared proportions of preventive
      visits that included diet/exercise counseling for pregnant women versus non
      pregnant women and performed multivariable logistic regression models to estimate
      odds ratios. Providers reported counseling pregnant women about diet/exercise
      during 17.9 % of preventive care visits compared to 22.6 % of visits for non
      pregnant women (P < 0.01, adj. OR 0.8, 95 % CI 0.7, 1.0). Overweight/obese
      pregnant (vs. non-pregnant) women were significantly less likely to receive
      diet/exercise counseling (adj. OR 0.7, CI 0.5, 0.9) as were women seen by OB/GYNs
      versus non-OB/GYNs (adj. OR 0.4, CI 0.3, 0.5). Our findings suggest that provider
      reported diet/exercise counseling rates during preventive care visits for women
      of childbearing age vary by overweight/obesity and pregnancy statuses, as well as
      by provider specialty. Our data suggest that there may be missed opportunities to
      provide diet/exercise counseling and that increasing rates of counseling could
      result in improved maternal and infant health outcomes. 

PMID- 24307057
TI  - Lower- extremity biomechanics and maintenance of vertical-jump height during
      prolonged intermittent exercise.
AB  - CONTEXT: Potential biomechanical compensations allowing for maintenance of
      maximal explosive performance during prolonged intermittent exercise, with
      respect to the corresponding rise in injury rates during the later stages of
      exercise or competition, are relatively unknown. OBJECTIVE: To identify lower
      extremity countermovement-jump (CMJ) biomechanical factors using a principal
      components approach and then examine how these factors changed during a 90-min
      intermittent-exercise protocol (IEP) while maintaining maximal jump height.
      DESIGN: Mixed-model design. SETTING: Laboratory. PARTICIPANTS: Fifty-nine
      intermittent-sport athletes (30 male, 29 female) participated in experimental and
      control conditions. INTERVENTIONS: Before and after a dynamic warm-up and every
      15 min during the 1st and 2nd halves of an individually prescribed 90-min IEP,
      participants were assessed on rating of perceived exertion, sprint/cut speed, and
      3-dimensional CMJ biomechanics (experimental). On a separate day, the same
      measures were obtained every 15 min during 90 min of quiet rest (control). MAIN
      OUTCOME MEASURES: Univariate piecewise growth models analyzed progressive changes
      in CMJ performance and biomechanical factors extracted from a principal
      components analysis of the individual biomechanical dependent variables. RESULTS:
      While CMJ height was maintained during the 1st and 2nd halves, the body descended
      less and knee kinetic and energetic magnitudes decreased as the IEP progressed.
      CONCLUSIONS: The results indicate that vertical-jump performance is maintained
      along with progressive biomechanical changes commonly associated with decreased
      performance. A better understanding of lower-extremity biomechanics during
      explosive actions in response to IEP allows us to further develop and
      individualize performance training programs.

PMID- 24307058
TI  - Human mesenchymal stromal cells modulate T-cell responses through TNF-alpha
      mediated activation of NF-kappaB.
AB  - Although mesenchymal stromal cells (MSCs) possess the capacity to modulate immune
      responses, little is known about the mechanisms that underpin these processes. In
      this study, we show that immunosupression is mediated by activation of nuclear
      factor kappa B (NF-kappaB) in human MSCs. This pathway is activated by TNF-alpha
      that is generated following TCR stimulation of T cells. Inhibition of NF-kappaB
      through silencing of IkappaB kinase beta or the TNF-alpha receptor abolishes the
      immunosuppressive capacity of MSCs. Our data also indicate that MSC-associated NF
      kappaB activation primarily leads to inhibition of T-cell proliferation with
      little effect on expression of the activation markers CD69 and CD25. Thus, our
      data support the hypothesis that the TNF-alpha/NF-kappaB signalling pathway is
      required for the initial priming of immunosuppressive function in human MSCs.
      Interestingly, drugs that interfere with NF-kappaB activation significantly
      antagonise the immunoregulatory effect of MSCs, which could have important
      implications for immunosuppression regimens in the clinic. 

PMID- 24307059
TI  - Assessment of adrenocortical activity and behavior of the collared anteater
      (Tamandua tetradactyla) in response to food-based environmental enrichment.
AB  - One of the current standard approaches to the study of animal welfare is
      measuring hypothalamic-pituitary-adrenal activity, frequently in association with
      behavioral assessment. We studied the effects of food-based environmental
      enrichment on adrenocortical activity and behavior in zoo-housed collared
      anteaters (Tamandua tetradactyla; n = 5). We successfully validated measurements
      of fecal cortisol metabolites (FCMs) using an 11-oxoetiocholanolone enzyme
      immunoassay by stimulating (ACTH injection) and suppressing (dexamethasone
      administration) adrenocortical activity. Three months later, we subjected animals
      to an ABA-type experiment (three 6-week periods): pre-enrichment (routine diet:
      A), enrichment (modified diet: B), and post-enrichment (routine diet: A) periods.
      We assessed adrenocortical activity by collecting individual feces three times a
      week (total number of samples: 228), and evaluated behavior by performing 3 days
      of behavioral observations per period (with a total of 3,600 behavioral data
      points for the individuals studied). Statistical analysis revealed changes in FCM
      concentrations (ug/g) over the periods (3.04 +/- 0.68, 2.98 +/- 0.66, and 4.04 +/
      0.90, respectively). Additionally, it showed that the number of FCM peaks was
      highly reduced during enrichment; meanwhile active natural behaviors were
      significantly increased. We consider that these changes in response to food-based
      environmental enrichment improved the welfare of individual zoo-housed collared
      anteaters. This research might contribute to in situ and ex situ studies on the
      physiology and behavior of this endemic South American species.

PMID- 24307060
TI  - Epigallocatechin-3-gallate, a green tea catechin, protects the heart against
      regional ischemia-reperfusion injuries through activation of RISK survival
      pathways in rats.
AB  - Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has
      been shown to modulate numerous molecular targets in the setting of inflammation.
      This study aimed to determine whether EGCG protects against regional myocardial
      ischemia/reperfusion (I/R) injuries and its underlying mechanisms involving the
      role of reperfusion injury salvage kinase (RISK) pathways (PI3K-Akt and ERK 1/2)
      and GSK-3beta or apoptotic kinases (p38 and JNK). The rats were subjected to I/R
      injuries consisting of 30 min ischemia followed by 2 h reperfusion. EGCG (10
      mg/kg, intravenously) was administered alone or along with wortmannin (PI3K
      inhibitor, 0.6 mg/kg, intravenously) 5 min before the onset of reperfusion.
      Wortmannin was administered 10 min before the reperfusion. Infarct size was
      measured at the end of the reperfusion. The phosphorylation of Akt, GSK-3beta,
      and MAPK kinases (ERK1/2, P38 and JNK) was determined by Western blotting after
      10 min of reperfusion. EGCG reduced the infarct size compared with the control
      (25.4 +/- 9.2 versus 43.2 +/- 8.2 %, p < 0.05). Wortmannin alone did not affect
      the infarct size, but abolished the EGCG-induced infarct size limiting effect,
      indicating that EGCG may protect the heart by modulating the PI3K-Akt. EGCG
      significantly enhanced the phosphorylation of Akt and GSK-3beta but not ERK1/2,
      while it reduced that of p38 and JNK. These results suggest that EGCG has a
      protective effect against regional myocardial I/R injuries through activation of
      the RISK pathway and attenuation of p38 and JNK. EGCG may have cardioprotective
      effects in patients undergoing surgeries prone to myocardial I/R injuries.

PMID- 24307061
TI  - Nanobiomaterials for pharmaceutical and medical applications.

PMID- 24307063
TI  - Optimizing the safety of surgery, before surgery.

PMID- 24307062
TI  - Elevation of serum tumor necrosis factor alpha in patients with periprosthetic
      osteolysis: a case-control study.
AB  - BACKGROUND: Periprosthetic osteolysis is the leading reason for THA revision. The
      relationship of serum biomarkers with severe radiographic periprosthetic
      osteolysis has not been defined but may be important to direct future research
      and clinical therapeutics. QUESTIONS/PURPOSES: We determined whether there was an
      association between measurable inflammatory markers (high-sensitivity C-reactive
      protein [hsCRP]) or inflammatory mediators (tumor necrosis factor alpha [TNF
      alpha], IL-1beta, IL-6, receptor activator of nuclear factor kappaB ligand
      [RANKL], and osteoprotegerin [OPG]) and periprosthetic osteolysis. METHODS: We
      identified 15 patients with THAs scheduled for revision surgery because of severe
      periprosthetic osteolysis. For each study patient, a nonosteolytic, pain-free
      control patient with THAs was identified and matched for age, sex, time since
      initial THA, acetabular and femoral component prosthesis material, and prosthesis
      wear within 1.0 mm/year using a manual wear analysis technique. Overall, the
      study and control patients had a mean wear rate of 0.25 mm/year since index THA.
      There were no differences in baseline characteristics between study and control
      patients in age, sex, BMI, Charlson Comorbidity Index, time since initial THA,
      UCLA activity score, and acetabular and femoral component type. Serum hsCRP, IL
      1beta, IL-6, TNF-alpha, RANKL, and OPG were measured by ELISA in duplicate
      assays. Differences in values were assessed using the Wilcoxon rank-sum test.
      RESULTS: Median TNF-alpha levels were higher in study patients than in controls
      (7.1 pg/mL [SD, 11.6 pg/mL] versus 1.5 pg/mL [SD, 1.3 pg/mL]) (p < 0.01). Median
      IL-6 levels tended to be higher in study patients than in controls (8.9 pg/mL
      [SD, 13.2 pg/mL] versus 3.5 pg/mL [SD, 0.7 pg/mL]) (p = 0.09). The other serum
      inflammatory proteins and mediators of bone turnover were not different between
      groups. CONCLUSIONS: TNF-alpha is elevated in patients with osteolysis compared
      to matched controls. The role of TNF-alpha and its potential as a target of
      nonsurgical therapy to prevent osteolysis warrant further investigation in
      larger, prospective studies.

PMID- 24307064
TI  - CORR Insights((r)): Is sternocleidomastoid muscle release effective in adults
      with neglected congenital muscular torticollis?

PMID- 24307065
TI  - Painful forearm mass in a 75-year-old man.

PMID- 24307066
TI  - CORR Insights(r): Meniscal injury after adolescent anterior cruciate ligament
      injury: how long are patients at risk?

PMID- 24307067
TI  - Elderly patients have similar outcomes compared to younger patients after
      minimally invasive surgery for spinal stenosis.
AB  - BACKGROUND: Older patients undergo surgery for lumbar spinal stenosis in great
      numbers, but as a result of substantial diagnostic and surgical heterogeneity,
      the impact of age on results after surgery is poorly defined. QUESTIONS/PURPOSES:
      We compared groups of patients younger and older than 70 years with relative
      clinical and surgical homogeneity to determine differences in (1) interval
      improvement in Oswestry Disability Index (ODI) at 6 weeks, 6 months, and 12
      months postoperatively and (2) perioperative adverse events. METHODS: We
      performed a subgroup analysis of an ongoing prospective observational study.
      Patients were divided based primarily on age (younger than 70 years [n = 68] and
      70 years or older [n = 41]) and secondarily on procedure (minimally invasive
      decompression alone or decompression and instrumented fusion). With the exception
      of age and American Society of Anesthesiologists status, the two age groups were
      similar (p > 0.3) in baseline demographics and ODI. Mean pre- and postoperative
      ODI were compared between groups at 6 weeks, 6 months, and 12 months.
      Perioperative adverse events were also compared. RESULTS: At all time intervals,
      both younger and older patients demonstrated (p = 0.05 to < 0.001) improvements
      in ODI. At the 1-year mark, no differences in ODI were demonstrated between the
      younger and older patients for decompression only (21 versus 26 [p = 0.29]) or
      decompression and fusion (19 versus 18 [p = 0.97]). Interval improvement in ODI
      was not different between younger and older patients at any time point for
      decompression only (6 weeks: -18 versus -20 [p = 0.66]; 6 months: -21 versus -17
      [p = 0.41]; 12 months: -21 versus -15 [p = 0.29]) or decompression and fusion (6
      weeks: -11 versus -12 [p = 0.58]; 6 months: -21 versus -22 [p = 0.69]; 12 months:
      -23 versus -27 [p = 0.97]). There were no differences in perioperative adverse
      events between groups (p = 0.67). CONCLUSIONS: When clinical and surgical
      heterogeneity is minimized, improvements in terms of disability as measured by
      the ODI and the frequency of adverse events after surgery in elderly patients
      with lumbar spinal stenosis are comparable to those of younger patients. For
      patients with focal lumbar spinal stenosis, age alone should not dissuade us from
      considering surgical intervention if otherwise indicated. LEVEL OF EVIDENCE:
      Level III, therapeutic study. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24307068
TI  - CORR Insights(r): Symptomatic pulmonary embolus after joint arthroplasty:
      stratification of risk factors.

PMID- 24307069
TI  - Prevalence of work-related dermatitis in the working population: authors'
      response to letter from Rosenman and Fussman.

PMID- 24307070
TI  - Three-dimensional compressible and stretchable conductive composites.
AB  - Three-dimensional (3D) conductive composites with remarkable flexibility,
      compressibility, and stretchability are fabricated by solution deposition of thin
      metal coatings on chemically modified, macroscopically continuous, 3D
      polyurethane sponges, followed by infiltration of the metallic sponges with
      polydimethylsiloxane (PDMS). These low-cost conductive composites are used as
      high-performance interconnects for flexible and stretchable light-emitting diode
      (LED) arrays, even with severe surface abrasion or cutting. 

PMID- 24307071
TI  - Calcium phosphate scaffolds mimicking the gradient architecture of native long
      bones.
AB  - The synthesis of beta-tricalcium phosphate (beta-TCP) scaffolds offering both the
      macroporous inner structure required for proper in vivo degradation and a non
      macroporous outer structure for the enhancement of mechanical properties
      continues to be a challenge. The hypothesis of this study was to realize
      biomimetic beta-TCP scaffolds with a macroporous inner structure and a compact
      outer structure using a lost wax casting technique. The porosity, macropore size,
      interconnectivity of the inner porous structure, and diameter of the outer
      compact structure were adjusted to specific values using a three-dimensional wax
      printer to manufacture the wax molds for the casting process. After the slip
      casting, the wax was pyrolyzed and the specimens were sintered. The resulting
      graded beta-TCP scaffolds (porous + compact) were characterized and compared with
      beta-TCP scaffolds with overall apparent macropores (only porous) and samples
      without macropores (only compact). The porosity and the compressive strength of
      the only compact, porous + compact, and only porous beta-TCP samples were 31.4 +/
      0.4 vol %, 55.6 +/- 0.9 vol %, and 66.9 +/- 0.4 vol % and 192 +/- 7 MPa, 36 +/-
      2 MPa, and 9 +/- 1 MPa, respectively. The macropore size was 500 um and the
      micropore size was up to 10 um, both featuring a completely open porous
      structure. From these results, we conclude that the lost wax casting technique
      offers an excellent method for the fabrication of beta-TCP scaffolds with an
      inner macroporous structure and compact outer structure which mimics the
      cancellous and cortical structure of natural bone.

PMID- 24307072
TI  - Health for profit?

PMID- 24307073
TI  - Growth counseling: A dialogue with Howard Clinebell.
AB  - This interview describes an emerging tenor in pastoral psychology, growth
      counseling. Philosophically cultivated by the Human Potentials Movement, this
      school of counseling has genetic components in biblical theology, as well as
      intrapsychic and interpersonal psychotherapy. Church-related issues are also
      linked, especially crisis intervention models for the laity and the pastoral
      counselor's unique vantage for ministry. In addition to these characteristics,
      the "dialogue" underscores two other concerns many health care professionals
      share: (1) a deemphasis of psychopathology via a renewed emphasis of the human
      "growth drive"; and (2) the therapeutic complementarity of affirmation vis-a-vis
      empathic confrontation. 

PMID- 24307074
TI  - Phenomenological methodology in the human sciences.
AB  - The author suggests that phenomenological methodology differs from traditional
      methodologies both in purpose and procedure. The task of a phenomenological
      researcher is to "see" the logic or meaning of an experience, for any subject,
      rather than to discover causal connections or patterns of correlation. The nature
      of the task demands extensive study of a small sample, allowing the subjects to
      speak for themselves and to reveal the logic of their experience as lived. The
      author reviews verification procedures relevant to phenomenological studies and
      discusses the limitations inherent in phenomenological research. 

PMID- 24307075
TI  - Mary and femininity: A psychological critique.
AB  - This essay uses Freud to interpret the symbolism and theology of Mary in modern
      Catholicism. In her role as the mother of believers, Mary functions to place the
      Christian in the position of a child who receives illusory gratification from the
      mother. In her role as model for Christians to emulate, Mary functions to place
      the Christian in the position of receptivity and dependence which Freud
      associated with femininity. Reinterpreting Freud from a feminist perspective, I
      suggest that the kind of femininity Mary represents serves to perpetuate
      patriachal social structures and to inhibit full psychological maturity. 

PMID- 24307076
TI  - Fear of engulfment and the problem of identity.
AB  - Centuries ago, our ancestors had already intuited that death anxiety is
      unequivocally linked to introspection and the search for identity. In mythology,
      the image of heroes being engulfed by monsters was often used symbolically to
      describe the potential dangers associated with such search. The author gives an
      overview of hero-myths and legends with engulfment motifs and presents a critical
      appraisal of Carl G. Jung's interpretation of its symbolism and relationship to
      "heroism" (that is, mental health). The prophet Jonah is also studied to
      highlight another type of hero rarely alluded to by Jung. Finally, parallels are
      drawn throughout with the fear of engulfment as seen in psychotherapy. 

PMID- 24307077
TI  - Empyrean rebirthing: Miracle or menace?
AB  - The purpose of this article is to alert human services professionals to the
      potential psychological and physiological harm which may result from
      participation in rebirthing, a process sponsored by the Science of Mind Church.
      The author provides a personal account of a rebirthing workshop as well as an
      analysis of the physiological determinants of the experiences she had. Questions
      are raised regarding the ethics, safety, and responsibilities inherent in the
      promotion of an activity such as rebirthing. 

PMID- 24307078
TI  - Health counseling competencies needed by the minister.
AB  - The purpose of this study was to characterize current health counseling practices
      of the Church of Christ minister and to identify areas of needed health
      counseling competencies which should be addressed during professional preparation
      of the minister. The subjects who made up the sample for this study came from the
      population of active local ministers of the Churches of Christ who resided in the
      states of Arkansas, California, Oklahoma, Tennessee, and Texas.Specifically, it
      was found that the Church of Christ minister is most frequently called upon to
      offer counsel in the health-related areas of marital problems, patient
      counseling, death education, alcohol problems, drug use or abuse, and aging,
      respectively. It was also found that the majority of the ministers surveyed felt
      that their training for the ministry had not adequately prepared them to offer
      health counsel. The majority of the sample indicated that all health topics
      listed on the questionnaire should be required during initial preparation for the
      ministry. Other findings were also noted. 

PMID- 24307079
TI  - Toward a model for spirituality and alcoholism.
AB  - Spirituality is a significant factor in recovery from alcoholism, whatever
      definition of this condition one may use. One aspect of alcohol abuse is its
      apparent relationship to the balance between brain hemispheres. Excessive use of
      alcohol "anesthetizes" the object-based, language-oriented functions of the left
      hemisphere, associated with an "action mode" of consciousness. This allows
      greater engagement of the right-hemisphere "receptive mode," which is also
      associated with religious experience. A model of spirituality based on achieving
      a balance between hemisphere functions and modes of consciousness could provide a
      non-chemical alternative to excessive use of alcohol. 

PMID- 24307080
TI  - Comparison of ultrasound and magnetic resonance imaging parameters in predicting
      survival in isolated left-sided congenital diaphragmatic hernia.
AB  - OBJECTIVE: To compare test characteristics of ultrasound- and magnetic resonance
      imaging (MRI)-derived parameters in predicting newborn survival in cases of
      isolated left-sided congenital diaphragmatic hernia (CDH). METHODS: This was a
      retrospective study involving 85 fetuses with an isolated left CDH. All had
      detailed prenatal evaluation, prenatal care, delivery and postnatal care at a
      single institution. Ultrasound images were reviewed to allow calculation of the
      lung-to-head ratio (LHR) and the observed/expected LHR (O/E-LHR), and MRI images
      were reviewed to determine the observed/expected total lung volume (O/E-TLV) and
      the percent herniated liver (%HL). Univariable logistic regression was used to
      evaluate each parameter for its ability to predict survival. Receiver-operating
      characteristics (ROC) curves were constructed and test characteristics were
      determined for each parameter as a predictor of survival. RESULTS: The overall
      survival for all fetuses included was 65%. Pseudo-R(2) values for all parameters
      were similar and were statistically significant as predictors of survival, with
      %HL having the highest pseudo-R(2) , of 0.28. ROC curve analysis showed
      ultrasound-determined parameters (LHR and O/E-LHR) to have a similar area under
      the curve (AUC), of 0.70, whilst MRI parameters (O/E-TLV and %HL) had AUC values
      of 0.82 and 0.84, respectively. At ROC-curve-determined cut-off values, MRI
      parameters had better test characteristics than did ultrasound parameters. At a
      standardized 5% false-positive rate, %HL performed best, with a sensitivity of
      0.54 and a specificity of 0.95. At clinically employed cut-off values,
      sensitivity was similar for all parameters but MRI parameters provided the best
      combination of sensitivity and specificity, as evidenced by better likelihood
      ratios. CONCLUSIONS: A variety of measures have been proposed as antenatal
      predictors of survival in CDH. Ultrasound parameters function at a similar level,
      whereas MRI-determined parameters appear to offer better predictive value.

PMID- 24307081
TI  - Tertiary alcohols as substrates for S(N)2-like stereoinversion.
AB  - Rewrite the textbooks! The stereospecific bimolecular substitution reaction (SN
      2) is usually limited to primary and secondary electrophiles. The Shenvi group
      has developed a method in which tertiary alcohol substrates are converted into
      isocyanides with configurational inversion. Intriguingly, tertiary hydroxy groups
      react selectively in the presence of unprotected primary and secondary hydroxy
      groups. 

PMID- 24307082
TI  - Characterization of multiple-herbicide-resistant Italian ryegrass (Lolium perenne
      spp. multiflorum).
AB  - BACKGROUND: Multiple-herbicide resistance in Lolium perenne spp. multiflorum has
      evolved in many areas in Oregon. To manage the resistant populations, the
      resistance patterns must be determined. In this study, a population (CT)
      suspected to be resistant to sulfometuron and hexazinone was collected from a
      Christmas tree plantation. RESULTS: The CT population is resistant to at least
      six herbicides with four different mechanisms of action: atrazine (>16-fold),
      diuron (2.4-fold), glyphosate (7.4-fold), hexazinone (3.1-fold), imazapyr (1.8
      fold) and sulfometuron (>16-fold). Two mutations, Trp-591-Leu and Ser-264-Gly,
      were identified in the acetolactate synthase (ALS) and psbA gene respectively. No
      previously reported mutation in the 5-enolpyruvylshikimate-3-phosphate synthase
      (EPSPS) gene was found. Less shikimic acid accumulated in the CT plants than in
      the susceptible plants after treatment with glyphosate at 0.6 kg AE ha(-1) .
      CONCLUSION: This study suggests that the multiple resistance patterns of Lolium
      perenne spp. multiflorum populations can be complex, but that chemical control
      options to manage these populations exist. These remaining chemical options
      should be integrated with non-chemical management strategies to slow the spread
      of multiple-resistant biotypes in agroecosystems.

PMID- 24307083
TI  - A modeling and simulation study of the role of suspended microbial populations in
      nitrification in a biofilm reactor.
AB  - Many biological wastewater treatment processes are based on bacterial biofilms,
      i.e. layered aggregates of microbial populations deposited on surfaces.
      Detachment and (re-)attachment leads to an exchange of biomass between the
      biofilm and the surrounding aqueous phase. Traditionally, mathematical models of
      biofilm processes do not take the contribution of the suspended, non-attached
      bacteria into account, implicitly assuming that these are negligible due to the
      relatively small amount of suspended biomass compared to biofilm biomass. In this
      paper, we present a model for a nitrifying biofilm reactor that explicitly
      includes both types of biomass. The model is derived by coupling a reactor mass
      balance for suspended populations and substrates with a full one-dimensional
      Wanner-Gujer type biofilm model. The complexity of this model, both with respect
      to mathematical structure and number of parameters, prevents a rigorous analysis
      of its dynamics, wherefore we study the model numerically.Our investigations show
      that suspended biomass needs to be considered explicitly in the model if the
      interests of the study are the details of the nitrification process and its
      intermediate steps and compounds. However, suspended biomass may be neglected if
      the primary interests are the overall reactor performance criteria, such as
      removal rates. Furthermore, it can be expected that changes in the biofilm area,
      attachment, detachment, and dilution rates are more likely to affect the
      variables primarily associated with the second step of nitrification, while the
      variables associated with the first step tend to be more robust.

PMID- 24307084
TI  - Optimal performance of the tryptophan operon of E. coli: a stochastic, dynamical,
      mathematical-modeling approach.
AB  - In this work, we develop a detailed, stochastic, dynamical model for the
      tryptophan operon of E. coli, and estimate all of the model parameters from
      reported experimental data. We further employ the model to study the system
      performance, considering the amount of biochemical noise in the trp level, the
      system rise time after a nutritional shift, and the amount of repressor molecules
      necessary to maintain an adequate level of repression, as indicators of the
      system performance regime. We demonstrate that the level of cooperativity between
      repressor molecules bound to the first two operators in the trp promoter affects
      all of the above enlisted performance characteristics. Moreover, the
      cooperativity level found in the wild-type bacterial strain optimizes a cost
      benefit function involving low biochemical noise in the tryptophan level, short
      rise time after a nutritional shift, and low number of regulatory molecules.

PMID- 24307085
TI  - [Support to pass away].

PMID- 24307086
TI  - [Legal ramifications of medical end-of-life decisions in dementia--orientational
      certainty through the latest decisions of the German Supreme Court?].
AB  - Taking care of dying people is one of the most difficult obligations of the
      physician, especially if these patients are suffering from dementia and
      accordingly when their current capacity to consent is arguable. In this field,
      numerous ethical and forensic problems arise that have to be considered. Legal
      medical end-of-life decisions that potentially shorten life (Sterbehilfe) are
      divided into two categories: direct "Sterbehilfe" refers to stopping life
      prolonging measures. Indirect "Sterbehilfe" describes the use of agents to
      alleviate symptoms of a terminally ill patient which may however, shorten life
      expectancy. A physician terminating a patient's life based on his own decision
      and authority of action always acts illegally. This paper describes the current
      discussion on this issue in Germany considering the medical and legal aspects of
      it while focussing on patients suffering from dementia and their ability to form
      and to articulate their own will. 

PMID- 24307087
TI  - [Psychopathological differentiation of depressive syndromes].
AB  - The historical contributions of Kurt Schneider, Karl Leonhard, Hans-Jorg
      Weitbrecht and Hubertus Tellenbach provide different concepts for a
      psychopathological differentiation of depressive syndromes. The current
      diagnostic systems ICD-10 and DSM-5 also contain categories for a differentiated
      classification of depressive disorders that trace back to the above historical
      concepts. The extensive diagnostic concepts of "depressive episode" or "major
      depression", however, are mainly based on the severity of symptomatology in terms
      of the number of symptoms and on their temporal duration. This approach could
      result in a lack of psychopathological differentiation and the limitation to a
      more syndromal and dimensional view of depression. In contrast, a differentiated
      typology of depressive phenomenology based on traditional psychopathological
      concepts could be useful both for clinical treatment decisions and for
      neurobiological research. 

PMID- 24307088
TI  - [Psychopathy in childhood and adolescence].
AB  - Personality disorders manifest themselves in stable deviations of personality
      traits that especially arise in negative interactions with others. Those typical
      dysfunctional interactions can be observed particularly in dissocial and
      antisocial personality disorders: adults with severe forms of personality
      disorders often showed specific symptoms in childhood and adolescence. Clinical
      researchers therefore demand a respective diagnosis of childhood and adolescent
      psychopathy. There is an extensive body of research on dissocial and borderline
      personality disorders in children and adolescents. To date the severe form of
      dissocial personality disorders, psychopathy, cannot be specifically classified.
      The transfer of this diagnosis to childhood and adolescence is crucial: based on
      the assumption of persistence and the risk of stigmatisation many clinicians
      refuse to diagnose psychopathy at a young age. On the other hand there are
      positive treatment outcomes that aim at symptom reduction from a very early age.
      The specification of dissocial personality disorders in childhood and adolescence
      may encourage the development of new treatments and the de-stigmatisation as well
      as qualify the dogged assumption of persistence of personality disorders. 

PMID- 24307089
TI  - [On the history of obsessive compulsive disorders: their place in the nosological
      classifications up to the beginning of the 20th century].
AB  - Influenced by French psychiatry, the first German works on obsessive-compulsive
      phenomena were published in the second half of the 19th century. First they were
      seen as one form of the unitary psychosis, later they became involved in the
      dispute about the concept of paranoia. The first German definition, proposed by
      Carl Westphal in 1877 and of crucial importance in the conceptual history of
      obsessive disorders as an illness (OCD) ever since, stood in this tradition.
      Still the adequate nosological classification of obsessive phenomena was still
      heavily disputed. As more and more varied forms of obsessive disorders were
      described, the highly unspecific concept of neurasthenia gained importance. Then
      degeneration theory was a widespread aetiological concept to integrate the large
      number of obsessive phenomena. Towards the end of the 19th century, when
      psychoanalysis emerged, psychological aspects started to interest psychiatrists
      and psychoanalytical suggestions like Sigmund Freud's concept of obsessional
      neurosis were discussed. However, none of these different nosological
      suggestions, nor any of the proposed definitions, found general approval. Above
      all the question to what extent affects were involved and whether certain
      phenomena were compulsive in nature or not remained the subject of (ongoing)
      controversy. This led to a variety of highly inconsistent aetiopathogenetic
      concepts being proposed. 

PMID- 24307090
TI  - [Drug safety in clinical practice--part 2: psychopharmacological treatment].

PMID- 24307091
TI  - [Communications of the Viktor von Weizsacker Society].

PMID- 24307092
TI  - Why do you fear the bogeyman? An embodied predictive coding model of perceptual
      inference.
AB  - Why are we scared by nonperceptual entities such as the bogeyman, and why does
      the bogeyman only visit us during the night? Why does hearing a window squeaking
      in the night suggest to us the unlikely idea of a thief or a killer? And why is
      this more likely to happen after watching a horror movie? To answer these and
      similar questions, we need to put mind and body together again and consider the
      embodied nature of perceptual and cognitive inference. Predictive coding provides
      a general framework for perceptual inference; I propose to extend it by including
      interoceptive and bodily information. The resulting embodied predictive coding
      inference permits one to compare alternative hypotheses (e.g., is the sound I
      hear generated by a thief or the wind?) using the same inferential scheme as in
      predictive coding, but using both sensory and interoceptive information as
      evidence, rather than just considering sensory events. If you hear a window
      squeaking in the night after watching a horror movie, you may consider plausible
      a very unlikely hypothesis (e.g., a thief, or even the bogeyman) because it
      explains both what you sense (e.g., the window squeaking in the night) and how
      you feel (e.g., your high heart rate). The good news is that the inference that I
      propose is fully rational and gives minds and bodies equal dignity. The bad news
      is that it also gives an embodiment to the bogeyman, and a reason to fear it. 

PMID- 24307094
TI  - The unusually strong stabilizing effects of glycine betaine on the structure and
      function of the oxygen-evolving Photosystem II complex.
AB  - Natural osmoregulatory substances (osmolytes) allow a wide variety of organisms
      to adjust to environments with high salt and/or low water content. In addition to
      their role in osmoregulation, some osmolytes protect proteins from denaturation
      and deactivation by, for example, elevated temperature and chaotropic compounds.
      A ubiquitous protein-stabilizing osmolyte is glycine betaine (N-trimethyl
      glycine). Its presence has been reported in bacteria, in particular
      cyanobacteria, in animals and in plants from higher plants to algae. In the
      present review we describe the experimental evidence related to the ability of
      glycine betaine to enhance and stabilize the oxygen-evolving activity of the
      Photosystem II protein complexes of higher plants and cyanobacteria. The osmolyte
      protects the Photosystem II complex against dissociation of the regulatory
      extrinsic proteins (the 18 kD, 23 kD and 33 kD proteins of higher plants and the
      9 kD protein of cyanobacteria) from the intrinsic components of the Photosystem
      II complex, and it also stabilizes the coordination of the Mn cluster to the
      protein cleft. By contrast, glycine betaine has no stabilizing effect on partial
      photosynthetic processes that do not involve the oxygen-evolving site of the
      Photosystem II complex. It is suggested that glycine betaine might act, in part,
      as a solute that is excluded from charged surface domains of proteins and also as
      a contact solute at hydrophobic surface domains. 

PMID- 24307095
TI  - Leaf cavity CO2 concentrations and CO2 exchange in onion, Allium cepa L.
AB  - Onion (Allium cepa L.) plants were examined to determine the photosynthetic role
      of CO2 that accumulates within their leaf cavities. Leaf cavity CO2
      concentrations ranged from 2250 MUL L(-1) near the leaf base to below atmospheric
      (<350 MUL L(-1)) near the leaf tip at midday. There was a daily fluctuation in
      the leaf cavity CO2 concentrations with minimum values near midday and maximum
      values at night. Conductance to CO2 from the leaf cavity ranged from 24 to 202
      MUmol m(-2) s(-1) and was even lower for membranes of bulb scales. The capacity
      for onion leaves to recycle leaf cavity CO2 was poor, only 0.2 to 2.2% of leaf
      photosynthesis based either on measured CO2 concentrations and conductance values
      or as measured directly by (14)CO2 labeling experiments. The photosynthetic
      responses to CO2 and O2 were measured to determine whether onion leaves exhibited
      a typical C3-type response. A linear increase in CO2 uptake was observed in
      intact leaves up to 315 MUL L(-1) of external CO2 and, at this external CO2
      concentration, uptake was inhibited 35.4+/-0.9% by 210 mL L(-1) O2 compared to 20
      mL L(-1) O2. Scanning electron micrographs of the leaf cavity wall revealed
      degenerated tissue covered by a membrane. Onion leaf cavity membranes apparently
      are highly impermeable to CO2 and greatly restrict the refixation of leaf cavity
      CO2 by photosynthetic tissue. 

PMID- 24307096
TI  - Efficiency of photosynthesis in continuous and pulsed light emitting diode
      irradiation.
AB  - The light utilization efficiency and relative photon requirement of
      photosynthesis in pulsed and continuous light from light emitting diodes (LEDs)
      has been measured. First, we chacterized the photon requirement of photosynthesis
      from light of LEDs that differ in spectral quality. A photon requirement of
      10.3+/-0.4 was measured using light from a 658 nm peak wavelength (22 nm half
      band width) LED over the range of 0-50 MUmol photons m(-2) s(-1) in 2 kPa O2 in
      leaves of tomato (Lycopersicon esculentum Mill., cv. VF36). Because the
      conversion of electrical power to photons increased with wavelength, LED lamps
      with peak photon output of 668 nm were most efficient for converting electricity
      to photosynthetically fixed carbon. The effect of pulsed irradiation on
      photosynthesis was then measured. When all of the light to make the equivalent of
      50 MUmol photons m(-2) s(-1) was provided during 1.5 MUs pulses of 5000 MUmol
      photons m(-2) s(-1) followed by 148.5 MUs dark periods, photosynthesis was the
      same as in continuous 50 MUmol photons m(-2) s(-1). When the pulse light and dark
      periods were lengthened to 200 MUs and 19.8 ms, respectively, photosynthesis was
      reduced, although the averaged photon flux density was unchanged. Under these
      conditions, the light pulses delivered 10(17) photons m(-2), which we calculate
      to be equivalent to the capacitance of PS I or PS II. Data support the theory
      that photons in pulses of 100 MUs or shorter are absorbed and stored in the
      reaction centers to be used in electron transport during the dark period. When
      light/dark pulses were lengthened to 2 ms light and 198 ms dark, net
      photosynthesis was reduced to half of that measured in continuous light. Pigments
      of the xanthophyll cycle were not affected by any of these pulsed light
      treatments even though zeaxanthin formation occurred when leaves were forced to
      dissipate an equal amount of continuous light. 

PMID- 24307097
TI  - Chlorophyll fluorescence changes at high temperatures induced by linear heating
      of greening barley leaves.
AB  - A relative decrease of the high temperature part (above 60 degrees C) of the
      chlorophyll fluorescence temperature curve during 3 h to 10 h greening period of
      barley (Hordeum vulgare L.) leaves was found to be concomitant to a decrease of
      Chl alb ratio and to a gradual increase of LHCP/core ratio found by
      electrophoresis and the ratio of granal to total length of thylakoid membranes.
      It is suggested that the high temperature part of the fluorescence temperature
      curve depends inversely on the relative amount of LHC II in thylakoid membranes. 

PMID- 24307093
TI  - The common origins of the pigments of life-early steps of chlorophyll
      biosynthesis.
AB  - The complex pathway of tetrapyrrole biosynthesis can be dissected into five
      sections: the pathways that produce 5-aminolevulinate (the C-4 and the C-5
      pathways), the steps that transform ALA to uroporphyrinogen III, which are
      ubiquitous in the biosynthesis of all tetrapyrroles, and the three branches
      producing specialized end products. These end products include corrins and
      siroheme, chlorophylls and hemes and linear tetrapyrroles. These branches have
      been subjects of recent reviews. This review concentrates on the early steps
      leading up to uroporphyrinogen III formation which have been investigated
      intensively in recent years in animals, in plants, and in a wide range of
      bacteria. 

PMID- 24307098
TI  - Complex formation in plant thylakoid membranes. Competition studies on membrane
      protein interactions using synthetic peptide fragments.
AB  - Thylakoid membranes of pea were used to study competition between extra-membrane
      fragments and their parental membrane-bound proteins. Phosphorylated and
      unphosphorylated fragments of light harvesting complex II (LHC II) from higher
      plants were used to compete with LHC II for interactions with itself and with
      other thylakoid protein complexes. Effects of these peptide fragments of LHC II
      and of control peptides were followed by 80 K chlorophyll fluorescence
      spectroscopy of isolated thylakoids. The phosphorylated LHC II fragment competes
      with membrane-bound phosphoproteins in the phosphatase reaction. The same
      fragment accelerates the process of dark-to-light adaptation and decreases the
      rate of the light-to-dark adaptation when these are followed by fluorescence
      spectroscopy. In contrast, the non-phosphorylated LHC II peptide does not affect
      the rate of adaptation but produces results consistent with inhibition of
      formation of a quenching complex. In this quenching complex we propose that LHC
      II remains inaccessible to the LHC II kinase, explaining an observed decrease in
      LHC II phosphorylation in the later stages of the time-course of phosphorylation.
      The most conspicuous protein which is steadily phosphorylated during the time
      course of phosphorylation is the 9 kDa (psbH) protein. The participation of the
      phosphorylated form of psbH in the quenching complex, where it is inaccessible to
      the phosphatase, may explain its anomalously slow dephosphorylation. The
      significance of the proposed complex of LHC II with phospho-psbH is discussed. 

PMID- 24307099
TI  - Prolonged high light treatment of plant cells results in changes of the amount,
      the localization and the electrophoretic behavior of several thylakoid membrane
      proteins.
AB  - The effect of a 30 h high light treatment on the amount and the localization of
      thylakoid proteins was analysed in low light grown photoautotrophic cells of
      Marchantia polymorpha and Chenopodium rubrum. High light treatment resulted in a
      net loss of D1 protein which was accompanied by comparable losses of other
      proteins of the PS II core (reaction center with inner antenna). LHC II proteins
      were not reduced correspondingly, indicating that these complexes are less
      affected by prolonged high light. High light influenced the distribution of PS II
      components between the grana and the stroma region of the thylakoid membrane,
      probably by translocation of the respective PS II proteins. Additionally,
      modifications of several thylakoid proteins were detected in high light treated
      cells of C. rubrum. These effects are discussed in relation to photoinhibitory
      damage and repair processes. 

PMID- 24307100
TI  - A possible calcium binding site in D1 protein: A fluorescence and FTIR study of
      the interaction between lanthanides and a synthetic peptide.
AB  - A peptide ranging from residue 229 to 240 of the D1 protein of Photosystem (PS)
      II was synthesized and lanthanides were used as candidates of calcium.
      Fluorescence and FTIR spectroscopy were used to test the conformational
      adaptation after lanthanide additions. Fluorescence spectroscopy showed that the
      synthetic peptide provides lanthanide binding site, and that glutamic acids are
      involved in lanthanide binding. Resolution enhancement techniques were combined
      with band curve-fitting procedures to quantitate the FTIR spectral information
      from the amide 1 bands. The relative areas of these component bands indicate that
      lanthanide induced a substantial decrease in the amount of unordered structure
      and turns, while a corresponding increase in the amount of alpha-helix and 'open
      loop' was also observed. This indicates that a relatively compact structure of
      the synthetic peptide is formed if lanthanides are applied. The results may
      reflect on the physiological and biochemical function of calcium in PS II,
      including preventing D1 from trypsin digestion. 

PMID- 24307103
TI  - Allelopathic polyacetylenes fromCentaurea repens (Russian knapweed).
AB  - The allelopathic weed Russian knapweed (Centaurea repens) was found to contain
      polyacetylenes VIII-XIV in the roots. Dose vs. response of the root length
      elongation against lettuce, alfalfa, barnyard grass, and red millet showed IX to
      be active. Closely related isomers were not active. Examination of the soil
      surrounding the Russian knapweed roots revealed the presence of IX in sufficient
      concentration to have an appreciable effect on the surrounding plant community. 

PMID- 24307102
TI  - MicroRNA-128 regulates the differentiation of rat bone mesenchymal stem cells
      into neuron-like cells by Wnt signaling.
AB  - Bone marrow mesenchymal stem cells (BMSCs) are a source of multipotent stem cells
      ideally suited for various cell-based therapies. BMSCs can differentiate into
      neuron-like cells under the appropriate conditions. MicroRNAs are members of a
      family of noncoding small RNAs that regulate gene expression at the
      posttranscriptional level, either by inhibiting mRNA translation or by promoting
      mRNA degradation. MicroRNAs play an important role in the differentiation of
      BMSCs into neurons. MicroRNA-128, a brain-enriched microRNA, was recently found
      to be necessary in the neural differentiation of BMSCs. Studies have shown that
      Wnt signaling pathway is involved in regulating MSC differentiation. Our goal
      here was to investigate whether microRNA-128 can regulate the differentiation of
      BMSCs through modulation of Wnt3a, a key component of the Wnt signaling pathway.
      By means of dual-luciferase reporter assay, we describe for the first time that
      by binding to a specific site in the 3'-UTR of Wnt3a in BMSCs, downregulated
      microRNA-128 may lead to the neural differentiation of mesenchymal stem cells.
      Transfection of microRNA-128 mimic decreased the nerve cell markers and Wnt3a
      expression levels. On the other hand, the inhibition of microRNA-128
      significantly elevated the nerve cell markers as well as the Wnt3a expression
      levels. This suggests that microRNA-128 acts as an endogenous attenuator of BMSCs
      differentiation into neurons. 

PMID- 24307104
TI  - Cuticular hydrocarbons of gregarious and solitary locustsLocusta migratoria
      cinerascens.
AB  - The cuticular hydrocarbons ofLocusta migratoria cinerascens-larvae and adults,
      males and females, gregarious and solitaries-have been investigated by combined
      gas chromatography-mass spectrometry. The hydrocarbons comprise 52-78% of the
      cuticular lipids and are divided inton-alkanes (28.7-47.3%), 3-, 4-, and 5
      methylalkanes (11.3-15.8%), internally branched monomethylalkanes (13.7-19.9%),
      and internally branched dimethylalkanes (19.8-35.9%) with seven or nine
      methylenes between the two branch points. While the sexual dimorphism does not
      seem to be reflected in the cuticular hydrocarbon composition, clear quantitative
      variations favoring the longest chain alkanes have been observed between
      gregarious and solitary locusts, thus revealing a new phase character in these
      insects. 

PMID- 24307105
TI  - Western avocado leafroller,Amorbia cuneana (Walsingham), (Lepidoptera:
      Tortricidae) : Discovery of populations utilizing different ratios of sex
      pheromone components.
AB  - The most effective lure for maleAmorbia cuneana (Walsingham) in Orange, Ventura,
      and Riverside counties of California was previously found to be a 1?1 ratio of
      (E,E)-10,12- and (E,Z)-10,12-tetradecadien-1-ol acetates. In subsequent field
      tests in San Diego and Santa Barbara counties, this lure was ineffective.
      Analysis of sex pheromone glands (SPG) of femaleA. cuneana from these two
      counties showed theEE:EZ ratio to be about 1?9 and synthetic lures of this
      composition were highly attractive in these areas. Analysis of the SPG of a
      number of females from both areas showed that there were three population types:
      two in the low ratio areas possessed 37 and 58%EZ, and the third in the high
      ratio areas possessed 89%EZ. 

PMID- 24307106
TI  - Beneficial arthropod behavior mediated by airborne semiochemicals : I. Flight
      behavior and influence of preflight handling ofMicroplitis croceipes (Cresson).
AB  - Oriented responses ofMicroplitis croceipes (Cresson) to airborne odors of
      actively feedingHeliothis zea (Boddie) larvae were observed in a flight tunnel.
      The behavior ofM. croceipes prior to and during sustained, oriented flights was
      videotaped and analyzed in detail. Preflight exposure of the parasitoid to feces
      and other components of the plant-host complex were found to be vital in
      effective flight behavior, while maturation of the parasitoid had little effect.
      The increased frequency of oriented flight that resulted from preflight exposure
      of a plant-host complex persisted for at least 24 hr. 

PMID- 24307101
TI  - Conundrum of pathogenesis of diabetic cardiomyopathy: role of vascular
      endothelial dysfunction, reactive oxygen species, and mitochondria.
AB  - Diabetic cardiomyopathy and heart failure have been recognized as the leading
      causes of mortality among diabetics. Diabetic cardiomyopathy has been
      characterized primarily by the manifestation of left ventricular dysfunction that
      is independent of coronary artery disease and hypertension among the patients
      affected by diabetes mellitus. A complex array of contributing factors including
      the hypertrophy of left ventricle, alterations of metabolism, microvascular
      pathology, insulin resistance, fibrosis, apoptotic cell death, and oxidative
      stress have been implicated in the pathogenesis of diabetic cardiomyopathy.
      Nevertheless, the exact mechanisms underlying the pathogenesis of diabetic
      cardiomyopathy are yet to be established. The critical involvement of
      multifarious factors including the vascular endothelial dysfunction,
      microangiopathy, reactive oxygen species (ROS), oxidative stress, mitochondrial
      dysfunction has been identified in the mechanism of pathogenesis of diabetic
      cardiomyopathy. Although it is difficult to establish how each factor contributes
      to disease, the involvement of ROS and mitochondrial dysfunction are emerging as
      front-runners in the mechanism of pathogenesis of diabetic cardiomyopathy. This
      review highlights the role of vascular endothelial dysfunction, ROS, oxidative
      stress, and mitochondriopathy in the pathogenesis of diabetic cardiomyopathy.
      Furthermore, the review emphasizes that the puzzle has to be solved to firmly
      establish the mitochondrial and/or ROS mechanism(s) by identifying their most
      critical molecular players involved at both spatial and temporal levels in
      diabetic cardiomyopathy as targets for specific and effective
      pharmacological/therapeutic interventions. 

PMID- 24307107
TI  - Studies on identification and syntheses of insect pheromones XXII : Sex pheromone
      of poplar twig clearwing mothParanthrene tabaniformis rott-Structure and
      synthesis.
AB  - (E,Z)-3,13-Octadecadien-1-ol (la) was identified as the sex pheromone from the
      poplar twig clearwing moth,Paranthrene tabaniformis, females by gas
      chromatography-mass spectrometry analysis, synthesis, and laboratory bioassays.
      In the field tests, a trap baited with 200 MUg synthetic la caught more male
      moths than two live female moths. 

PMID- 24307108
TI  - Field studies on chemically mediated behavior in land hermit crabs: Volatile and
      nonvolatile odors.
AB  - Land hermit crabs,Coenobita rugosis, were tested in the field in Costa Rica for
      behavioral responses to odors. Volatile odors associated with horse feces, fruit,
      and honey attracted crabs within minutes. Odors from dead gastropod flesh were
      not immediately attractive, but after aging, odors from a variety of flesh
      sources attracted crabs. Crabs fed actively upon the materials that attracted
      them. Feeding behavior was stimulated by components of fruit juice and fresh
      gastropod flesh juices of less than 10,000 daltons, honey, a 0.5 M sucrose
      solution, and a saturated solution of tyrosine. Twenty additional amino acid
      solutions tested at 0.1 M concentration were weak feeding stimulants at best.
      Chemical cues controlled feeding behavior, but not shell acquisition;C. rugosis
      were not differentially attracted to flesh odors or to living gastropods whose
      shells they occupied. 

PMID- 24307109
TI  - Propaganda substances in the cuckoo antLeptothorax kutteri and the slave
      makerHarpagoxenus sublaevis.
AB  - This paper reports the first discovery of "propaganda substances" in a workerless
      inquiline ant, the European myrmicineLeptothorax kutteri Buschinger. These
      substances are used by the parasite queen as a chemical weapon for defense
      against hostile workers of the host speciesL. acervorum. The substances also have
      an unusual behavioral effect: they cause host workers to attack each other, and
      they therefore appear to override nestmate recognition in host colonies.
      Laboratory experiments show that the source of these substances is the Dufour's
      gland of theL. kutteri queen. Our experiments also confirm the hypothesis that
      the closely related slave-making antHarpagoxenus sublaevis uses its Dufour's
      gland secretions as a chemical weapon during slave raids and colony foundation.
      The behavioral effect of these slave-maker secretions is identical to that ofL.
      kutteri queens. 

PMID- 24307110
TI  - Predator deterrence by mandibular gland secretions of bees (Hymenoptera:
      Apoidea).
AB  - Volatile lipids from the mandibular gland secretions of bees (Hymenoptera:
      Apoidea) are potent olfactory repellents of foraging ants (Formica,
      Crematogaster) in biologically relevant contexts and quantities. In contrast,
      differential success in capture of bee and fly prey by predatory asilid flies
      (Efferia), reduviid bugs (Apiomerus), and arachnids (Agelenopsis, Argiope) is
      better explained by prey size than by chemical repellence, aposematism, or
      possession of a sting. Supernormal doses of some allomones, applied to worker
      honeybees (Apis mellifera) that were fed toArgiope aurantia spiders, elicted more
      frequent preenvenomation pauses following ensnarement but did not significantly
      increase other prey-handling times. These pauses merely delayed the bee's demise.
      Mandibular gland secretions of solitary bees augment their other secondary
      defenses in at least two contexts: (1) during intranest encounters when repelling
      intruding ants, and (2) retaliation delivered to their arthropodan predators
      which, if the bee is nearly too large for the predator to handle, may allow the
      bee to escape. 

PMID- 24307111
TI  - Plant allelochemicals and insect parasitoids effects of nicotine onCotesia
      congregata (say) (Hymenoptera: Braconidae) andHyposoter annulipes (Cresson)
      (Hymenoptera: Ichneumonidae).
AB  - Parasitoids developing within tobacco hornworms or fall army-worms exhibit
      significant differences in development and survival depending on whether their
      hosts fed on nicotine-free or nicotine-containing diets. The effects of nicotine
      were more severe on the relatively less adapted parasitoid,H. annulipes than the
      specialist parasitoid,Cotesia congregata. Labeled alkaloid originally placed in
      herbivore diet was incorporated in several parasitoid tissues. These results
      suggest that interactions between plant allelochemicals and parasitoids should be
      considered in the development of theory on insect herbivory and plant defense. 

PMID- 24307112
TI  - Effects of comsumption of high and low nicotine tobacco byManduca sexta
      (Lepidoptera: Sphingidae) on survival of gregarious endoparasitoidCotesia
      congregata (Hymenoptera: Braconidae).
AB  - The significance of nicotine in the three trophic level interaction involving
      tobacco (Nicotiana tabacum), the tobacco hornworm (Manduca sexta), and the
      parasitoidCotesia congregata was investigated in field plots of two varieties of
      tobacco which had about a 10-fold difference in their nicotine content. WhileM.
      sexta mortality, rates of parasitism byC. congregata, and the total number ofC.
      congregata larvae produced per host were similar on each of the two varieties,
      the number of parasitoids reaching adult-hood on the low nicotine treatment was
      nearly twice that on the high nicotine treatment. This difference was due to the
      significantly greater proportion of parasitoid larvae which failed to emerge from
      the host or that died prior to pupation after emerging from hosts which fed on
      the high nicotine variety. A greater proportion of larvae from hosts which fed on
      the low nicotine tobacco died as pupae. No treatment differences occurred for
      either sex of the parasitoid in individual dry weight, longevity, or pupal
      development time, except that female pupal duration was prolonged in the high
      nicotine treatment. These results support the suggestion that plant
      allelochemicals, which may function to provide plant resistance against pest
      herbivores, can be detrimental to natural enemies of the pest. 

PMID- 24307113
TI  - Laser microbeam studies of role of amphid receptors in chemosensory behavior of
      nematodeCaenorhabditis elegans.
AB  - Amphid sensilla, historically considered the primary chemosensory structures of
      nematodes, were found to be necessary for the detection of only one of the six
      chemical stimuli that were tested. Only the attraction to cAMP was eliminated by
      damaging the two lateral lips, which bear the amphid sensilla. The inner labial
      sensilla, one of which occurs on each of the six lips, are probably the primary
      receptor structures for the other chemical stimuli. Damaging all six lips, which
      should destroy all anterior chemosensory input, not only eliminted the attraction
      to sodium and chloride ions, but reversed the nematodes' response to them.
      Nematodes with all six lips destroyed showed reversal behavior when exposed to
      these attractants. Nematodes with damage to all six lips appeared to recover much
      of their normal chemosensory function within 24 hr after treatment. 

PMID- 24307114
TI  - Effects of cuticular duvane diterpenes from green tobacco leaves on tobacco
      budworm (Lepidoptera: Noctuidae) oviposition.
AB  - Five cuticular chemical components isolated from the green leaves of tobacco
      introductions (TIs) and a commercial tobacco cultivar were tested for their
      effects on tobacco budworm,Heliothis virescens (F), oviposition in cage
      bioassays, and field experiments. These chemicals were sprayed onto budworm
      resistant TI 1112 tobacco which produces low levels of most cuticular components.
      Individual duvane diterpenes (alpha- and beta-4,8,13-duvatrien-1-ols and alpha-
      and beta-4,8,13-duvatriene-1,3-diols) increased tobacco budworm egg laying on
      sprayed TI 1112 plants.cis-Abienol, docosanol, and docosanyl myristate were
      inactive. 

PMID- 24307115
TI  - Sex pheromone ofGrapholita funebrana occurrence ofZ-8- andZ-10-Tetradecenyl
      acetate as secondary components.
AB  - Z-8-Dodecenyl acetate (Z8-12?Ac),E-8-dodecenyl acetate (E8-12?Ac),Z-8
      tetradecenyl acetate (Z8-14?Ac),Z-10-tetradecenyl acetate (Z10-14?Ac), andZ-8
      dodecen-1-ol (Z8-12?OH) were identified in the proportions 100?1?30?5?2 in female
      sex gland extracts ofGrapholita funebrana, accompanied by saturated acetates from
      12 to 20 carbons with tetradecyl acetate predominating.Z10-14?Ac has not
      previously been described as a lepidopteran sex pheromone component. Best
      attraction of males is obtained withZ8-12?Ac in the presence of a higher
      proportion ofE8-12?Ac than in the female. Inclusion of the 14-carbon acetates did
      not augmentG. funebrana catches but inhibitedG. molesta. On the other hand,
      addition ofZ8-12?OH at the level optimal forG. molesta reduced attraction ofG.
      funebrana. 

PMID- 24307116
TI  - Aggregation of larvae ofBlattella germanica (L.) by lactic acid present in
      excreta.
AB  - Lactic acid has been identified in extracts of filter paper "conditioned" by the
      German cockroach,Blattella germanica (L.). One-to two-week old larvae aggregated
      on filter paper wetted with solutions of lactic acid. 

PMID- 24307117
TI  - The female sex pheromone of sugarcane stalk borer,Chilo auricilius identification
      of four components and field tests.
AB  - Four pheromonal components have been detected in ovipositor washings and
      volatiles from female sugarcane stalk borers,Chilo auricilius Dudgeon
      (Lepidoptera: Pyralidae), using combined gas chromatography-electroantennography.
      The components have been identified as (I) (Z)-7-do-decenyl acetate, (II) (Z)-8
      tridecenyl acetate, (III) (Z)-9-tetradecenyl acetate, and (IV) (Z)-10
      pentadecenyl acetate by comparison of their gas chromatographic behavior with
      that of synthetic standards. In field tests carried out in northern India during
      1982-1984, a combination of II, III, and IV in their naturally occurring ratio
      (8?4?1) was shown to provide a highly attractive synthetic source for trap use.
      (Z)-7-Dodecenyl acetate was found to reduce catches of maleC. auricilius, both
      when dispensed with the other three components and when released from dispensers
      surrounding a trap baited with the other three components. 

PMID- 24307118
TI  - Vitamin a deficiency modifies response of predatory miteAmblyseius potentillae to
      volatile kairomone of two-spotted spider mite,Tetranychus urticae.
AB  - A volatile kairomone of the two-spotted spider mite,Tetranychus urticae, elicits
      a searching response of the phytoseiid predatorAmblyseius potentillae, only when
      the predator is reared on a carotenoid-free diet. However, after addition of
      crystalline beta-carotene or vitamin A acetate to the predator's rearing diet
      this searching response was absent. Because vitamin A and beta-carotene are
      indispensable nutrients for diapause induction, the carotenoid-deficient
      predators increase their fitness by searching for two-spotted spider mites, when
      other spider mites are unavailable. Two-spotted spider mites, among others,
      contain the carotenoids required for diapause induction, but are an inferior prey
      due to the dense webbing they produce. When the predators have carotenoids at
      their disposal, they do better by searching for other spider mites that are more
      profitable in terms of reproductive success. Such a prey is the European red
      spide mite,Panonychus ulmi. The volatile kairomone of this prey elicits a
      searching response of the predator whether it has a carotenoid deficiency or not.

PMID- 24307119
TI  - Defensive mechanisms of loblolly and shortleaf pine against attack by southern
      pine beetle,Dendroctonus frontalis Zimmermann, and its fungal
      associate,Ceratocystis minor (Hedgecock) Hunt.
AB  - Loblolly and shortleaf pine growing on a single site in the North Carolina
      piedmont were examined to determine similarities and differences in their
      defensive mechanisms against the southern pine beetle,Dendroctonus frontalis
      Zimmermann, and its fungal associate,Ceratocystis minor (Hedgecock) Hunt. Both
      species responded to wounding and fungal inoculation by forming a hypersensitive
      lesion around the wound site. There were significantly less soluble sugars and
      more monoterpenes in the lesion tissue than in unwounded inner bark. The two
      species were similar in resin flow rate and inner bark soluble sugar content, but
      the loblolly pines had thicker bark, longer hypersensitive lesions, and a higher
      concentration of inner bark monoterpenes. Inner bark monoterpene composition was
      also significantly different between the two pine species. It is hypothesized
      that two different defensive strategies against southern pine beetle attack may
      be utilized. 

PMID- 24307120
TI  - Necrodols: Anti-insectan terpenes from defensive secretion of carrion beetle
      (Necrodes surinamensis).
AB  - Two compounds recently isolated from the defensive gland ofNecrodes surinamensis,
      alpha-and beta-necrodol, first representatives of a new category of monoterpenes
      (the necrodanes), are shown to be repellent to ants and other insects and
      irritating to cockroaches and flies. The compounds doubtless play a defensive
      role inNecrodes. The possible long-range applied significance of research on
      insect repellents is discussed. 

PMID- 24307121
TI  - Sex pheromone ofEupoecilia ambiguella female: Analysis and male response to
      ternary blend.
AB  - Sex gland extracts and washes ofEupoecilia ambiguella contain 10-20 ng/female of
      the primary sex pheromone componentZ-9-dodecenyl acetate (Z9-12?Ac), accompanied
      by a number of related compounds. These areE-9-dodecenyl acetate (E9-12?Ac),Z-9
      dodecen-1-ol (Z9-12?OH), saturated acetates of 12, 16, 18, and 20 carbons, and
      traces of a doubly unsaturated acetate, tentatively identified as a 9,11
      dodecadienyl acetate. Octadecyl acetate predominates among the pheromone-related
      components, making up 1-2, occasionally 20-30 times the amount ofZ9-12?Ac. The
      same compounds were also found in field-collected females and in effluvia.Z-9
      Undecenyl acetate, which is a male attractant on its own, was also found in a
      sample of female effluvia. A hierarchy is observed in the ethological function of
      the pheromone components.Z9-12?Ac is an attractant forE. ambiguella males.
      Dodecyl acetate (12?Ac) is not attractive on its own but augments male catch when
      added to the main attractant. Addition of 18?Ac augments attraction only when
      bothZ9-12?Ac and 12?Ac are present. Windtunnel tests demonstrate that 18?Ac also
      raises the disorientation threshold, as previously shown for 12?Ac. Other
      compounds, with the possible exception of additional saturated acetates, had
      either no effect on trap catch or, in the case ofE9-12?Ac,Z9-12?OH, andE-9,11
      dodecadienyl acetate, were inhibitory above a certain level. A blend of roughly
      equal parts ofZ9-12?Ac, 12?Ac, and 18?Ac provides the best attractant blend forE.
      ambiguella known to date. 

PMID- 24307122
TI  - Allelopathic research of subtropical vegetation in Taiwan : III. Allelopathic
      exclusion of understory byLeucaena leucocephala (Lam.) de Wit.
AB  - Leucaena leucocephala plantations in Kaoshu, southern Taiwan, exhibit, after
      several years of growth, a unique pattern of weed exclusion beneathLeucaena
      canopy. The pattern has been observed in manyLeucaena plantations in Taiwan and
      is particularly pronounced in the area where a substantial amount ofLeucaena
      litter has accumulated on the ground. Field data showed that the phenomenon was
      primarily not due to physical competition involving light, soil moisture, pH, and
      nutrients. Instead, aqueous extracts ofLeucaena fresh leaves, litter, soil, and
      seed exudate showed significantly phytotoxic effects on many test species,
      including rice, lettuce,Acacia confusa, Alnus formosana, Casuarina glauca,
      Liquidambar formosana, andMimosa pudica. However, the extracts were not toxic to
      the growth ofLeucaena seedlings. The decomposing leaves ofLeucaena also
      suppressed the growth of the aforementioned plants grown in pots but did not
      inhibit that ofLeucaena plants. By means of paper and thin-layer chromatography,
      UV-visible spectrophotometry, and high-performance liquid chromatography, 10
      phytotoxins were identified. They included mimosine, quercetin, and gallic,
      protocatechuic,p-hydroxybenzoic,p-hydroxyphenylacetic, vanillic, ferulic,
      caffeic, andp-coumaric acids. The mature leaves ofLeucaena possess about 5% dry
      weight of mimosine, the amount varying with varieties. The seed germination and
      radicle growth of lettuce, rice, and rye grass were significantly inhibited by
      aqueous mimosine solution at a concentration of 20 ppm, while that of the forest
      species mentioned was suppressed by the mimosine solution at 50 ppm or above.
      However, the growth ofMiscanthus floridulus andPinus taiwanensis was not
      suppressed by the mimosine solution at 200 ppm. The seedlings ofAgeratum
      conzoides died in mimosine solution at 50 ppm within seven days and wilted at 300
      ppm within three days. It was concluded that the exclusion of understory plants
      was evidently due to the allelopathic effect of compounds produced byLeucaena.
      The allelopathic pattern was clearly shown in the area with a heavy accumulation
      ofLeucaena leaf litter, which was a result of drought and heavy wind influence. 

PMID- 24307123
TI  - Isolation and characterization of glucocapparin inIsomeris arborea nutt.
AB  - Isomeris arborea (Capparaceae), is the only woody caper endemic to southern
      California and northern Baja. Methylglucosinolate, also known as glucocapparin,
      was the only glucosinolate found inI. arborea organs by paper chromatography of
      the thiourea derivatives and was quantitatively determined by gas chromatography
      by hydrolytic products. The concentration of glucocapparin ranged from an average
      of 4.6 mg/g wet weight in mature leaves to 5.2 mg/g wet weight in immature
      leaves. Buds averaged 6.2 mg/g wet weight and capsule walls 1.8 mg/g wet weight.
      Seeds contained an average of 14.3 mg/g wet weight of glucocapparin.
      Glucocapparin concentration was found to vary significantly among the mature
      leaves of individuals within a single population. This compound is known to be
      deleterious to nonadapted herbivores and may be implicated in the chemical
      defense mechanism ofI. arborea. 

PMID- 24307124
TI  - Euphydryas anicia (Lepidoptera: Nymphalidae) utilization of iridoid glycosides
      fromCastilleja andBesseya (Scrophulariaceae) host plants.
AB  - Iridoid glycosides were found to be sequestered by natural populations
      ofEuphydryas anicia after ingestion from the host plantsBesseya alpina, B.
      plantaginea, andCastilleja integra. Both major iridoids ofB. alpina, cataipol and
      aucubin, were found in butterfly populations where this was the only host plant.
      The catalpol-aucubin ratio was higher in the butterflies than in the host plant.
      AnE. anicia population which uses bothB. plantaginea andC. integra as host plants
      was found to sequester cataipol as well as another iridoid, macfadienoside.
      Macfadienoside was the major iridoid ofC. integra, while catalpol esters were the
      major iridoids ofB. plantaginea. Although it was a major sequestered iridoid,
      catalpol was a minor constituent in both host plants. The macfadienoside-catalpol
      ratio in the butterflies from this population was highly variable, and there
      appeared to be both sex and individual variation in host plant and/or iridoid
      glucoside utilization byE. anicia. Although other iridoids were present in the
      host plants, none was sequestered in more than trace amounts. 

PMID- 24307125
TI  - Potentially defensive proteins in mature seeds of 59 species of tropical
      leguminosae.
AB  - A survey of 59 species of tropical legume seeds revealed high interspecific
      variation in proteinaceous capacity to inhibit bovine trypsin (a digestive
      enzyme) and to agglutinate human (type B, Rh positive) and laboratory rabbit red
      blood cells. The legume subfamily Mimosoideae was conspicuous for the absence of
      seeds with very weak trypsin inhibition. Congenerics sometimes differed strongly
      from each other with respect to both trypsin inhibition and
      phytohemagglutination. Half the species of seeds displayed no hemagglutinating
      capacity with one or the other kinds of red blood cells, and in only 27% of the
      30 cases where there was some activity did the same species of seed actively
      agglutinate both species of red blood cells. A species of seed that had
      hemagglutinating capacity was almost invariably associated with moderate to high
      levels of trypsin inactivation. While it has been long known that a great
      diversity of small toxic and potentially defensive molecules occur in legume
      seeds and that one species of seed often contains several of them, we now feel
      that it is reasonable to consider legume seeds as also containing a high
      diversity of potentially toxic protein molecules. A single seed is likely to
      contain, at the least, three to four classes of defensive compounds, any or all
      of which, or some in combination, may be the cause of a seed being rejected by a
      potential seed predator. 

PMID- 24307126
TI  - Toxicities of host secondary compounds to eggs of theBrassica specialistDasineura
      brassicae.
AB  - The toxicities of selected host secondary plant substances to eggs of theBrassica
      specialistDasineura brassicae were estimated in a laboratory test.
      Isothiocyanates (ITCs) and 1-cyano-2-phenylethane, autolysis products of
      glucosinolates, were more toxic than a "green leaf alcohol,"cis-3-hexen-1-ol,
      found in numerous plant families. The most toxic compound, 2-phenylethyl ITC,
      occurs in all investigatedBrassica hosts ofD. brassicae. However, the less
      suitableBrassica hosts additionally release comparatively large amounts of allyl
      ITC. This suggests that even a crucifer specialist may be restricted in its use
      of particular hosts due to their compositions and concentrations of glucosinolate
      compounds. 

PMID- 24307127
TI  - Identification of sex pheromone produced by female sweetpotato weevil,Cylas
      formicarius elegantulus (Summers).
AB  - A sex pheromone of the sweetpotato weevil,Cylas formicarius elegantulus
      (Summers), was obtained from collections of volatiles from virgin females, and
      pheromone was isolated by means of liquid and gas chromatography. The
      purification procedure was monitored by quantitative laboratory and field
      bioassays and the compound was identified as (Z)-3-dodecen-1-ol (E)-2-butenoate
      by means of spectroscopic and microchemical methods. Synthesis, followed by
      laboratory and field bioassays, showed that the biological activity of the
      synthetic material was qualitatively and quantitatively indistinguishable from
      that of the purified natural product. 

PMID- 24307128
TI  - Behavioral and growth responses of specialist herbivore,Homoeosoma electellum, to
      major terpenoid of its host,Helianthus SPP.
AB  - The responses of a sunflower specialist,Homoeosoma electellum, the sunflower
      moth, to the terpenoids produced by its host plant,Helianthus, were measured.
      Larvae were reared on synthetic diet containing one of three concentrations of
      the dominant sesquiterpene lactone found in glandular trichomes ofH.
      maximilliani. Treatments were initiated at each of three larval ages. Pupal
      weight was significantly reduced, but the effect diminished as the larvae aged.
      Survival and development time were unaffected by various treatments. In
      behavioral tests, larvae showed no preference for untreated synthetic diet
      compared to diet containing the secondary compound at a concentration of 1% by
      dry weight. When the concentration was raised to 5%, all but last-instar larvae
      showed a significant preference for the untreated diet. A second behavioral test
      measured the damage done to whole florets and an array of floral parts offered to
      larvae of different ages. The damage pattern of floral tissues changed as the
      larvae grew older, demonstrating that the willingness of larvae to eat tissues
      contaminated with trichome contents increased with age. The value of the
      glandular trichome contents as a defense againstH. electellum is discussed. 

PMID- 24307129
TI  - Behavior ofHeliothis virescens (F.) in presence of oviposition deterrents from
      elderberry.
AB  - Extracts prepared from elderberry,Sambucus simpsonii Rehd., leaves with either
      acetone, dichloromethane, distilled water, ethanol, hexane, or methanol deterred
      oviposition byHeliothis virescens (F.) on treated substrates in the laboratory.
      Doses of the aqueous extract equivalent to as little as 0.8 mg of leaves/cm2 of
      oviposition substrate were effective in reducing egg deposition. There was no
      significant difference in the mean number of landings on extract-treated and
      untreated surfaces. When either the antennae, proboscis, or the metathoracic legs
      were removed from female moths, there was no significant effect on oviposition on
      paper towels treated with elderberry leaf-water extract in laboratory bioassays,
      but in field cages, moths without these appendages deposited significantly fewer
      eggs on treated leaves of tobacco plants, a preferred host. There was no evidence
      that elderberry leaf-water extract affected mating byH. virescens. 

PMID- 24307130
TI  - Allelopathic influence ofSorghum bicolor on weeds during germination and early
      development of seedlings.
AB  - The allelopathic interaction between sorghum [Sorghum bicolor (L.) Moench] and 10
      species of grass and broadleaf weeds was investigated. Germination of weed seeds
      was slightly inhibited or stimulated, depending on species, when incubated in
      closed Petri dishes with germinating sorghum. Subsequent radicle and hypocotyl or
      coleoptile elongation of weeds was significantly inhibited by the germinating
      sorghum. For weeds interplanted with sorghum and grown under greenhouse
      conditions. The inhibitory effect on some weed species was still evident after 2
      months of growth. Significant differences were found in the dry matter per weed
      plant grown in pots in proximity to sorghum vs. weeds grown in monoculture.
      Aqueous leachates from pots planted with sorghum alone or from a system in which
      sorghum roots protruded into water had strong allelopathic activity. These
      results indicate that water-soluble allelochemicals are produced by germinating
      sorghum seeds and that production of these substances continues during seedling
      growth. 

PMID- 24307131
TI  - Study of female sex pheromone of leopard moth,Zeuzera pyrina L. Isolation and
      identification of three components.
AB  - Three compounds have been identified in the abdominal tip extracts from the
      female leopard moth,Zeuzera pyrina L. Gas-liquid chromatography and mass
      spectroscopy data showed that (E, Z)-2, 13-octadecadien-1-ol acetate was the main
      component and that (Z)-13-octadecen-1-ol acetate and octadecan-1-ol acetate were
      secondary components. The electroanten-nographic responses of maleZ. pyrina to
      nanogram amounts of all four 2, 13-octadecadien-1-ol acetate isomers indicated
      that theE, Z isomer had the maximum activity. A strong EAG response was also
      recorded for (Z)-7-do-decen-1-ol acetate, which was not detected in the female
      extracts. 

PMID- 24307132
TI  - Sex-specific activity of (R)-(-)- and (S)- (+)-1,7-dioxaspiro[5.5]undecane, the
      major pheromone ofDacus oleae.
AB  - 1,7-Dioxaspiro[5.5]undecane (olean), the major component of the female sex
      attractant pheromone blend of the olive fruit flyDacus oleae (Gmelin) was shown
      to be released as a racemate. The response of males and females to pure (R)-(-)
      and (S)-(+)-enantiomers was tested under laboratory and field conditions. Males
      in laboratory and field tests responded only to (R)-(-)-olean, which functions as
      a sex attractant. Females responded only to (S)-(+)-olean in laboratory tests but
      not in the field. There are indications that the latter enantiomer fuctions as a
      short-range arrestant throughout the day and as an aphrodisiac in the process of
      mating. 

PMID- 24307133
TI  - Exploring skyline for both MS(E) -based label-free proteomics and HRMS
      quantitation of small molecules.
AB  - The MS(E) (where MS(E) is low energy (MS) and elevated energy (E) mode of
      acquisition) acquisition method commercialized by Waters on its Q-TOF instruments
      is regarded as a unique data-independent fragmentation approach that improves the
      accuracy and dynamic range of label-free proteomic quantitation. Due to its
      special format, MS(E) acquisition files cannot be independently analyzed with
      most widely used open-source proteomic software specialized for processing data
      dependent acquisition files. In this study, we established a workflow integrating
      Skyline, a popular and versatile peptide-centric quantitation program, and a
      statistical tool DiffProt to fulfill MS(E) -based proteomic quantitation.
      Comparison with the vendor software package for analyzing targeted
      phosphopeptides and global proteomic datasets reveals distinct advantages of
      Skyline in MS(E) data mining, including sensitive peak detection, flexible
      peptide filtering, and transparent step-by-step workflow. Moreover, we developed
      a new procedure such that Skyline MS1 filtering was extended to small molecule
      quantitation for the first time. This new utility of Skyline was examined in a
      protein-ligand interaction experiment to identify multiple chemical compounds
      specifically bound to NDM-1 (where NDM is New Delhi metallo-beta-lactamase 1), an
      antibiotics-resistance target. Further improvement of the current weaknesses in
      Skyline MS1 filtering is expected to enhance the reliability of this powerful
      program in full scan-based quantitation of both peptides and small molecules. 

PMID- 24307134
TI  - Fetal and placental vascular tumors: persistent fetal hyperdynamic status
      predisposes to poorer long-term neurodevelopmental outcome.
AB  - OBJECTIVE: To evaluate the association between fetal hemodynamic changes seen in
      the presence of vascular tumors of fetal or placental origin and risk of adverse
      pregnancy outcome. METHODS: All cases of placental chorioangioma, sacrococcygeal
      teratoma and pulmonary sequestration during a 10-year period were included.
      Ultrasound data and pregnancy and long-term neurodevelopmental outcomes were
      assessed in this cohort. A survival analysis was performed to assess the
      relationship between the cardiovascular profile score (CVPS) and adverse
      pregnancy outcome. RESULTS: There were 56 fetal or placental tumors, including 28
      chorioangiomas, 10 sacrococcygeal teratomas and 18 pulmonary sequestrations,
      diagnosed at a median gestation of 23 + 3 weeks. Abnormal CVPS (<= 8) was seen in
      30% of sacrococcygeal teratomas and in 46% of chorioangiomas, but in none of the
      pulmonary sequestration cases. Adverse pregnancy outcome occurred in 11 cases
      (three stillbirths, three neonatal deaths and five cases of developmental delay)
      and only in those cases in which the tumors were associated with a CVPS of <= 8.
      CONCLUSIONS: Certain fetal and placental vascular tumors are associated with
      cardiac dysfunction in fetal life. When the CVPS is low (<= 8), these cases are
      at increased risk of both fetal/neonatal demise as well as overt long-term
      neurodevelopmental disability. The long-term neurodevelopmental outcome should be
      formally and prospectively assessed in cases of fetal and placental vascular
      tumors.

PMID- 24307135
TI  - Prediction of the ageing of commercial lager beer during storage based on the
      degradation of iso-alpha-acids.
AB  - BACKGROUND: Iso-alpha-acids and their chemically modified variants are
      responsible for the bitterness of beer and play a disproportionately large role
      in the final quality of beer. The current study was undertaken to predict the
      degradation of commercial lager beers related to changes in the concentration of
      trans-iso-alpha-acids during storage by using high-pressure liquid
      chromatography. RESULTS: In the analysed beers the concentration of isohumulone
      (average concentration 28 mg L(-1)) was greater than that of isocohumulone (20 mg
      L(-1)) and isoadhumulone (10 mg L(-1)). The kinetic parameters, activation energy
      and rate constant, of the trans-iso-alpha-acids were calculated. In the case of
      dark beers, the activation energy for the degradation of trans-isocohumulones was
      found to be higher than for trans-isohumulones and trans-isoadhumulones, whereas
      in pale and alcohol-free beers activation energies for the degradation of the
      three trans isomers were similar. CONCLUSION: The loss of iso-alpha-acids can be
      calculated using the activation energy of the degradation of trans-iso-alpha
      acids and the temperature profile of the accelerated ageing. The results obtained
      in the investigation can be used in the beer industry to predict the alteration
      of the bitterness of beer during storage.

PMID- 24307136
TI  - Current approaches to managing fear of cancer recurrence; a descriptive survey of
      psychosocial and clinical health professionals.
AB  - OBJECTIVE: Fear of cancer recurrence (FCR) is common amongst cancer survivors and
      help with this problem is the most frequently reported unmet need in this
      population. This study investigated how FCR is perceived and managed by clinical
      health professionals (medical and nursing staff) and psychosocial professionals
      in oncology settings. METHODS: Clinical health professionals and psychosocial
      professionals in oncology settings received emailed invitations from their
      professional organisation to participate in an online survey. RESULTS: Data from
      77 clinical health professionals and 64 psychosocial professionals indicate that
      FCR is perceived as common and challenging to manage. Thirty-one percent of
      psychosocial professionals estimated FCR is present in >50% of cancer survivors
      seen in their practise. Only a minority (21%) of clinical staff reported always
      referring patients with high levels of FCR to psychosocial support. Strategies
      for managing FCR differed considerably amongst psychosocial professionals, and
      most reported that aspects of acceptance and commitment therapy and/or cognitive
      behaviour therapy were helpful. Greater than 99% of participants were interested
      in training to help patients manage FCR. CONCLUSIONS: Fear of cancer recurrence
      is commonly identified in oncology settings and a common focus of discussion in
      follow-up care. However, patients with high levels of FCR are not routinely
      referred to psychosocial staff, and barriers to referral to psychosocial care
      should be investigated. The diversity of approaches reported by psychosocial
      professionals suggests lack of consensus regarding management of FCR, indicating
      that the development effective, theoretical-based intervention and evidence-based
      intervention for FCR is a matter of priority.

PMID- 24307137
TI  - Spot drip application of dimethyl disulfide as a post-plant treatment for the
      control of plant parasitic nematodes and soilborne pathogens in grape production.
AB  - BACKGROUND: Plant parasitic nematodes and soilborne pathogens can reduce the
      overall productivity in grape production. Not all grape growers apply soil
      fumigants before planting, and there is no single rootstock resistant to all
      nematode species. The aim of this investigation was to evaluate the effect of
      dimethyl disulfide (DMDS) applied at 112, 224, 448 and 897 kg ha(-1) as a post
      plant treatment against soilborne plant parasitic nematodes and pathogens on the
      grape yield in established grapevines. RESULTS: In microplot and field trials,
      post-plant fumigation with DMDS controlled citrus (Tylenchulus semipenetrans),
      root-knot (Meloidogyne spp.), pin (Paratylenchus spp.) and ring (Mesocriconema
      xenoplax) nematodes in established Thomson Seedless grapevines. However, DMDS did
      not control the soilborne pathogens Pythium ultimum and Fusarium oxysporum. No
      indications of phytotoxicity were detected after post-plant fumigation with DMDS.
      In the field trial, grape yield was significantly higher with the lowest DMDS
      rate, but no difference among other rates was observed in comparison with the
      untreated control. CONCLUSION: Post-plant fumigation with DMDS controlled plant
      parasitic nematodes in established grapevines but was less efficacious against
      soilborne pathogens. Low rates of DMDS were sufficient for nematode control and
      increased the grape yield, probably without affecting beneficial soil organisms.
      Further research on evaluating the potential effect of DMDS against beneficial
      soil organisms is needed.

PMID- 24307139
TI  - Glutamate dysfunction associated with developmental cerebellar damage: relevance
      to autism spectrum disorders.
AB  - Neural abnormalities commonly associated with autism spectrum disorders include
      prefrontal cortex (PFC) dysfunction and cerebellar pathology in the form of
      Purkinje cell loss and cerebellar hypoplasia. It has been reported that loss of
      cerebellar Purkinje cells results in aberrant dopamine neurotransmission in the
      PFC which occurs via dysregulation of multisynaptic efferents from the cerebellum
      to the PFC. Using a mouse model, we investigated the possibility that
      developmental cerebellar Purkinje cell loss could disrupt glutamatergic
      cerebellar projections to the PFC that ultimately modulate DA release. We
      measured glutamate release evoked by local electrical stimulation using fixed
      potential amperometry in combination with glutamate selective enzyme-based
      recording probes in urethane-anesthetized Lurcher mutant and wildtype mice.
      Target sites included the mediodorsal and ventrolateral thalamic nuclei,
      reticulotegmental nuclei, pedunculopontine nuclei, and ventral tegmental area.
      With the exception of the ventral tegmental area, the results indicated that in
      comparison to wildtype mice, evoked glutamate release was reduced in Lurcher
      mutants by between 9 and 72% at all stimulated sites. These results are
      consistent with the notion that developmental loss of cerebellar Purkinje cells
      drives reductions in evoked glutamate release in cerebellar efferent pathways
      that ultimately influence PFC dopamine release. Possible mechanisms whereby
      reductions in glutamate release could occur are discussed.

PMID- 24307141
TI  - Rhodium(I)-catalyzed cyclization of allenynes with a carbonyl group through
      unusual insertion of a C-O bond into a rhodacycle intermediate.
AB  - Rhodium(I)-catalyzed cyclization of allenynes with a tethered carbonyl group was
      investigated. An unusual insertion of a C?O bond into the C(sp(2) )-rhodium bond
      of a rhodacycle intermediate occurs via a highly strained transition state.
      Direct reductive elimination from the obtained rhodacyle intermediate proceeds to
      give a tricyclic product containing an 8-oxabicyclo[3.2.1]octane skeleton, while
      beta-hydride elimination from the same intermediate gives products that contain
      fused five- and seven-membered rings in high yields. 

PMID- 24307140
TI  - Electroanalysis may be used in the vanillin biotechnological production.
AB  - This study shows that electroanalysis may be used in vanillin biotechnological
      production. As a matter of fact, vanillin and some molecules implicated in the
      process like eugenol, ferulic acid, and vanillic acid may be oxidized on
      electrodes made of different materials (gold, platinum, glassy carbon). By a
      judicious choice of the electrochemical method and the experimental conditions
      the current intensity is directly proportional to the molecule concentrations in
      a range suitable for the biotechnological process. So, it is possible to imagine
      some analytical strategies to control some steps in the vanillin biotechnological
      production: by sampling in the batch reactor during the process, it is possible
      to determine out of line the concentration of vanillin, eugenol, ferulic acid,
      and vanillic acid with a gold rotating disk electrode, and low concentration of
      vanillin with addition of hydrazine at an amalgamated electrode. Two other
      possibilities consist in the introduction of electrodes directly in the batch
      during the process; the first one with a gold rotating disk electrode using
      linear sweep voltammetry and the second one requires three gold rotating disk
      electrodes held at different potentials for chronoamperometry. The last proposal
      is the use of ultramicroelectrodes in the case when stirring is not possible. 

PMID- 24307142
TI  - The matter of the heart.

PMID- 24307143
TI  - The pastoral challenge of an abusive situation.
AB  - This paper explores a ministerial response to congregants who have abused or
      neglected their child. I begin by distinguishing the three major secular
      responses to this kind of family problem: casework, counseling, and therapy, and
      go on to note how all of the above are limited in their effectiveness by the
      objective, causal, explanatory framework within which they operate. I suggest
      that a pastor can take the same family facts and help those involved to
      understand and respond to them concretely as they are experienced. The paper
      concludes with an exploration of this alternative approach within a religious
      vocabulary of prayer and increased inwardness. 

PMID- 24307144
TI  - Marriage and ministry in midlife women.
AB  - This study of 15 midlife women seminarians or clergy and 13 of their husbands
      focuses upon the tension between a commitment to family life and a commitment to
      ordained ministry. The women were preparing to become Protestant clergy or were
      already in this vocation, while their husbands were middle-class, successful
      professional people. The study examines the impact of the new cultural self
      development ethic upon the lives and religious faith of the women. Husbands'
      responses to the wives' changes are considered, and suggestions are made to
      supervising judicatories regarding assistance that may be given to the couples. 

PMID- 24307145
TI  - Re-visioning resurrection: St. Paul and Swedenborg.
AB  - St. Paul's "spiritual body" is envisaged as imaginal body, the wordimaginal
      standing for the intermediate realm of beings and events in Neoplatonism and
      Sufism. Swedenborg's world of spirits and angels conforms to this view and so is
      seen as contributing to a richer understanding of St. Paul in the sense of a
      "good" docetism. Crucial in this kind of revisioning the mystery of resurrection
      is the creative power of visionary imagination, which, in turn, is inseparable
      from the reality of the soul as thesitus of visionary events. 

PMID- 24307146
TI  - The denial of death and the out-of-the-body experience.
AB  - The out-of-the-body experience is a phenomenon which continues to be reported and
      continues to be interpreted in many ways. It seems, however, that more attention
      is given to finding a spiritual base for this occurrence than a psychological
      understanding of it. This paper considers the psychological forces of denial as a
      suitable explanation for the OBE and suggests that these experiences may be
      understood as hallucinations caused by traumatic events rather than genuine
      previews of the afterlife. That is: "Do these people transcend their bodies and
      also time and space to acquire these experiences, or could it be that nothing has
      been transcended at all save the need to deny death and thus transcend its feared
      consequence, which is 'not being'?" 

PMID- 24307147
TI  - Hermeneutics in a medical center.
AB  - By focusing onhermeneutics anddialogue, this article clarifies the distinctive
      contribution that pastoral and psychotherapeutic interventions have to make in
      the healing process. It is shown how the hermeneutical process discloses the
      meaning of events through the interpretation of texts that arise spontaneously in
      the lives of individuals and groups. Texts may range from individual fantasies
      and dreams to sacred histories recorded in scriptures. When the meaning of life
      events is explored in dialogue through symbolic texts, we term that process
      "dialogical hermeneutics." Effective dialogical hermeneutics requires the use of
      three techniques: (1) presence in the caring relationship, (2) dialogue toward
      meaning, and (3) offering alternative interpretation. 

PMID- 24307148
TI  - Manipulating nanoscale interactions in a polymer nanocomposite for chiral control
      of linear and nonlinear optical functions.
AB  - The design, synthesis, and supramolecular organization of a nanocomposite in
      which nanoscale excitonic interactions between quantum dots and the chiral
      polymer dramatically enhance the optical activity is reported. This material is
      highly suitable for application in the emerging field of chiral photonics. 

PMID- 24307149
TI  - Nucleotide sequences of transfer RNA genes in the Pisum sativum chloroplast DNA.
AB  - Eight transfer RNA (tRNA) genes which were previously mapped to five regions of
      the Pisum sativum (pea) chloroplast DNA (ctDNA) have been sequenced. They have
      been identified as tRNA(Val)(GAC), tRNA(Asn)(GUU), tRNA(Arg)(ACG),
      tRNA(Leu)(CAA), tRNA(Tyr)(GUA), tRNA(Glu)(UUC), tRNA(His)(GUG), and
      tRNA(Arg)(UCU) by their anticodons and by their similarity to other previously
      identified tRNA genes from the chloroplast DNAs of higher plants or from E.
      gracilis. In addition,two other tRNA genes, tRNA(Gly) (UCC) and tRNA(Ile)(GAU),
      have been partially sequenced. The tRNA genes are compared to other known
      chloroplast tRNA genes from higher plants and are found to be 90-100% homologous.
      In addition there are similarities in the overall arrangement of the individual
      genes between different plants. The 5' flanking regions and the internal
      sequences of tRNA genes have been studied for conserved regions and consensus
      sequences. Two unusual features have been found: there is an apparent intron in
      the D-loop of the tRNA(Gly)(UCC), and the tRNA(Glu)(UUC) contains GATTC in its T
      loop. 

PMID- 24307150
TI  - The two genes for the small subunit of RuBP Carboxylase/oxygenase are closely
      linked in Chlamydomonas reinhardtii.
AB  - Ribulose bisphosphate carboxylase-oxygenase (Rubisco) is a key enzyme in the
      photosynthetic fixation of CO2 by the chloroplast. The synthesis of the enzyme is
      an example of the cooperation between the chloroplast and the nucleocytoplasmic
      compartments, as it is assembled from subunits encoded in the two respective
      genomes. I have used a synthetic oligonucleotide probe to isolate the nuclear
      Rubisco small subunit genes (rbcS) directly from a genomic library of
      Chlamydomonas reinhardtii DNA. They constitute only a small family: there are two
      rbcS genes, and an additional related sequence, in the C. reinhardtii genome. All
      three are clustered within 11kb at a single locus, and should thus be
      particularly well suited for genetic manipulation. The pattern of expression of
      rbcS RNA is dependent on the growth conditions. 

PMID- 24307138
TI  - Consensus paper: pathological mechanisms underlying neurodegeneration in
      spinocerebellar ataxias.
AB  - Intensive scientific research devoted in the recent years to understand the
      molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are
      identifying new pathways and targets providing new insights and a better
      understanding of the molecular pathogenesis in these diseases. In this consensus
      manuscript, the authors discuss their current views on the identified molecular
      processes causing or modulating the neurodegenerative phenotype in
      spinocerebellar ataxias with the common opinion of translating the new knowledge
      acquired into candidate targets for therapy. The following topics are discussed:
      transcription dysregulation, protein aggregation, autophagy, ion channels, the
      role of mitochondria, RNA toxicity, modulators of neurodegeneration and current
      therapeutic approaches. Overall point of consensus includes the common vision of
      neurodegeneration in SCAs as a multifactorial, progressive and reversible
      process, at least in early stages. Specific points of consensus include the role
      of the dysregulation of protein folding, transcription, bioenergetics, calcium
      handling and eventual cell death with apoptotic features of neurons during SCA
      disease progression. Unresolved questions include how the dysregulation of these
      pathways triggers the onset of symptoms and mediates disease progression since
      this understanding may allow effective treatments of SCAs within the window of
      reversibility to prevent early neuronal damage. Common opinions also include the
      need for clinical detection of early neuronal dysfunction, for more basic
      research to decipher the early neurodegenerative process in SCAs in order to give
      rise to new concepts for treatment strategies and for the translation of the
      results to preclinical studies and, thereafter, in clinical practice. 

PMID- 24307151
TI  - Several biotic and abiotic elicitors act synergistically in the induction of
      phytoalexin accumulation in soybean.
AB  - Plants often respond to microbial infection by producing antimicrobial compounds
      called phytoalexins. Plants also produce phytoalexins in response to in vitro
      treatment with molecules called elicitors. Specific elicitors, including a hexa
      beta-glucosyl glucitol derived from fungal cell walls, the pectin-degrading
      enzyme endopolygalacturonic acid lyase, and oligogalacturonides obtained by
      either partial acid hydrolysis or enzymatic degradation of plant cell walls or
      citrus polygalacturonic acid, induce soybean (Glycine max. L.) cytoledons to
      accumulate phytoalexins. The experiments reported here demonstrate that the
      elicitor-active hexa-beta-glucosyl glucitol acts synergistically with several
      biotic and abiotic elicitors in the induction of phytoalexins in soybean
      cotyledons. At concentrations below 50 ng/ml, the hexa-beta-glucosyl glucitol
      does not induce significant phytoalexin accumulation. When assayed in combination
      with either endopolygalacturonic acid lyase or with a decagalacturonide released
      from citrus polygalacturonic acid by this lyase, however, the observed elicitor
      activity of the hexa-beta-glucosyl glucitol is as much as 35-fold higher than the
      sum of the responses of these elicitors assayed separately. A similar synergism
      was also demonstrated for the combination of the hexa-beta-glucosyl glucitol with
      dilute solutions of sodium acetate, sodium formate, or sodium propionate buffers.
      These buffers are thought to damage or kill plant cells, which may cause the
      release of oligogalacturonides from the plant cell wall. The results suggest that
      oligogalacturonides act as signals of tissue damage and, as such, can enhance the
      response of plant tissues to other elicitor-active molecules during the
      initiation of phytoalexin accumulation. 

PMID- 24307152
TI  - An under-methylated region in the spacer of ribosomal RNA genes of Lilium henryi.
AB  - Ribosomal RNA genes of Lilium henryi are almost completely methylated at CG and
      CNG sequences. A short under-methylated region was detected between 2.05 and 2.4
      kbp upstream of the 18S sequences. It included the only sites of digestion by
      four methylation-sensitive restriction endonucleases - PstI, Hae II, Eco RII and
      Hpa II. Only about 15%-20% of rDNA repeats from shoot meristem are susceptible to
      each of the enzymes. The same repeats are apparently cut by all enzymes and occur
      in contiguous blocks. Because the region involved is likely to include regulatory
      sequences it may be that under-methylation occurs specifically in active rDNA
      repeats. To test this, rDNA was examined from pollen mother cells at pachytene
      where transcription has fallen to near zero. Under-methylation levels here were
      similar to those in shoot meristem tissue. Thus methylation of this region is not
      the agent responsible for rDNA gene inactivation in pachytene cells and it does
      not occur immediately genes become inactive. Even so, sequences in this region
      might be prevented from becoming methylated in transcribing repeats. 

PMID- 24307153
TI  - The formation of R-prime deletion mutants and the identification of the symbiotic
      genes in Rhizobium fredii strain USDA191.
AB  - R-prime plasmids were formed between the plasmid of Rhizobium fredii strain
      USDA191 containing nodulation and nitrogen-fixation genes, pRjaUSDA191c, and
      pRL180, and RP1 derivative. R. fredii USDA191 contains four HindIII fragments
      that hybridize with an 8.7 kb EcoRI fragment that contains nodulation genes from
      R. meliloti. These four fragments are on pRjaUSDA191c and are 15.5 kb, 12.5 kb,
      6.8 kb, and 5.2 kb in size. A series of R-primes generated in E. coli of
      pRjaUSDA191c were transferred into a Nod(-) Nif(-) derivative of strain USDA191
      to determine which nodulation region is necessary for nodule formation.
      Transconjugants containing the 12.5 kb and the 6.8 kb HindIII fragments on
      segments of pRjaUSDA191c produced nodules on soybean plants. However,
      transconjugants containing the 12.5 kb HindIII fragment alone were unable to form
      nodules, suggesting that the 6.8 kb HindIII fragment or the 6.8 kb and the 12.5
      kb HindIII fragments together were needed for nodule formation. The 6.8 kb
      HindIII fragment was subcloned into the vector pVK102 and transferred into
      transconjugants containing no sequences homologous to R. meliloti nodulation DNA
      or to transconjugants containing only the 12.5 kb HindIII fragment. Nodules were
      formed on soybeans only when both the 12.5 kb and the 6.8 kb HindIII fragments
      were present in R. frediistrain USDA191. 

PMID- 24307154
TI  - Properties of the linear N1 and N2 plasmid-like DNAs from mitochondria of
      cytoplasmic male-sterile Sorghum bicolor.
AB  - The linear N1 and N2 plasmid-like DNAs were recovered from mitochondria of the
      IS1112C line of cytoplasmic male-sterile (CMS) Sorghum bicolor (S. bicolor).
      Molecular clones containing internal sequences of these plasmids were
      constructed. These clones were used to probe Southern blots of mitochondrial
      genomes from six CMS and five male-fertile (MF) lines of S. bicolor, as well as
      Southern blots of IS1112C chloroplast, IS1112C nuclear and kafir nuclear genomes.
      We found no evidence for integrated copies of N1 or N2 in any of the
      mitochondrial, chloroplast or nuclear genomes probed in this study. Our clones
      did detect an N1-homologous transcript of 3.1 kb and N2-homologous transcripts of
      3.9 and 1.4 kb in IS1112C mitochondrial RNA prepared from lines with and without
      nuclear, fertility-restoring genes.N1 and N2 DNAs were degraded by exonuclease
      III but were resistant to lambda exonuclease, presumably due to the presence of
      5' terminal proteins. We detected multimeric forms of N1 and N2 in Southern blots
      of unrestricted, IS1112C mitochondrial DNA (mtDNA). These forms apparently also
      had associated protein molecules. 

PMID- 24307156
TI  - The FREEDOM trial (AUGUST 2013).

PMID- 24307157
TI  - Electronic health records (JULY 2013).

PMID- 24307158
TI  - Q: Can an ARB be given to patients who have had angioedema on an ACE inhibitor?

PMID- 24307159
TI  - The conundrum of explaining breast density to patients.

PMID- 24307160
TI  - Dense breasts and legislating medicine.

PMID- 24307161
TI  - Ascites in a 42-year-old woman.

PMID- 24307162
TI  - Third universal definition of myocardial infarction: update, caveats,
      differential diagnoses.
AB  - Updated definitions of myocardial infarction (MI) reflect research on measuring
      cardiac troponin to diagnose MI. Elevations of this biomarker indicate cardiac
      injury but not always an acute coronary syndrome. Clinical judgment is needed to
      interpret increasingly sensitive biomarker assays appropriately. Here, we review
      the new MI definitions and the various causes of elevated troponin to enable
      physicians to differentiate acute coronary syndromes from other conditions. 

PMID- 24307163
TI  - Antiplatelet therapy to prevent recurrent stroke: Three good options.
AB  - Drugs that prevent platelets from sticking together-ie, aspirin, dipyridamole,
      and clopidogrel-are an important part of therapy to prevent recurrence of
      ischemic stroke of atherosclerotic origin. We discuss current indications for
      these drugs and review the evidence behind our current use of aspirin,
      dipyridamole, and clopidogrel. 

PMID- 24307164
TI  - Percutaneous lovastatin accelerates bone healing but is associated with
      periosseous soft tissue inflammation in a canine tibial osteotomy model.
AB  - Experimental studies have shown the ability of statins to stimulate bone
      formation when delivered locally or in large oral doses, however most have been
      studied in rodents. This anabolic effect is through the selective activation of
      BMP-2. Our purpose was to determine the effects of local treatment with
      lovastatin on bone healing in mammals as a preclinical animal model. We
      administered lovastatin (6 mg/kg) by percutaneous injection to a canine tibial
      osteotomy stabilized with external fixation. We found that lovastatin improved
      bone healing after a single injection into the fracture site assessed by serial
      radiography and histology at bone union. However, lovastatin treatment resulted
      in adverse local soft tissue inflammation. These results suggest that
      percutaneous lovastatin injection may be a useful adjuvant treatment over the
      course of bone healing to augment fracture repair, although further investigation
      into the mechanism of soft tissue adverse effects is warranted.

PMID- 24307165
TI  - Cardiac magnetic resonance before and after percutaneous pulmonary valve
      implantation.
AB  - PURPOSE: To measure the magnetic resonance (MR) artefact produced by a
      percutaneous pulmonary valve stent and to evaluate the changes in volumetric and
      functional right ventricle (RV) parameters due to percutaneous pulmonary valve
      implantation (PPVI). MATERIALS AND METHODS: A Melody valve was studied in vitro
      using clinical cardiac MR (CMR) sequences. In vivo, we analysed the CMR
      examinations obtained before and after PPVI of 27 consecutive patients. The
      echocardiography pressure gradient (PG) and catheter PG were measured. The
      Wilcoxon test was used for comparisons. RESULTS: In vitro, the least difference
      between artefact extent and actual valve size (0.1 mm) was obtained with a steady
      state free precession (SSFP) sequence. In vivo, RV end-diastolic volume
      (ml/m(2)), end-systolic volume (ml/m(2)) and ejection fraction (%) were 79 +/-
      42, 43 +/- 41 and 49 +/- 13 before PPVI and 64 +/- 21 (p = 0.054), 30 +/- 14 (p =
      0.021), and 54 +/- 12 (p = 0.018) 6 months after PPVI, respectively. The PG and
      regurgitation fraction (RF) were 36 +/- 15 mmHg and 14 +/- 18 % before PPVI and
      13 +/- 15 mmHg (p < 0.001) and 2 +/- 5 % (p = 0.013) after PPVI, respectively. No
      significant differences were found comparing the PG measured with CMR,
      echocardiography and catheter. CONCLUSIONS: We showed in vitro that the SSFP
      sequence produced the most accurate valve measurement. After PPVI, CMR showed a
      strong decrease of PG and RF with a significant improvement of RV function.

PMID- 24307166
TI  - [The effectiveness of health aid to West Africa: now more uncertain than ever].

PMID- 24307167
TI  - Assessing health literacy in rural settings: a pilot study in rural areas of Cluj
      County, Romania.
AB  - Health literacy improves knowledge and builds skills to help individuals make
      appropriate decisions regarding their health. Over the past 20 years, several
      studies have described associations between health literacy and health outcomes.
      With respect to Romania, evidence is scarce on the level of health literacy, as
      well as on its determinants. Thus, the objectives of this study were to briefly
      screen functional health literacy levels in a sample of rural inhabitants, to
      assess the relationship between health literacy and reported health status, as
      well as to explore health literacy determinants within this population. Data were
      collected between September-November 2010, in four villages in Cluj County,
      Romania, using a cross-sectional survey. The mean age of respondents in the
      sample was 56 years, with roughly half of respondents being retired. The brief
      screening of health literacy suggested inadequate to marginal levels within the
      sample. Significant associations were observed between health literacy score and
      education, and self-perceived health status, whereas the relationship between
      health literacy and gender, and the presence of a chronic disease was not
      statistically significant. Limited health literacy has been shown to be common in
      people who rated their health as poor, those who attended only middle school, and
      individuals lacking basic information about their body. In order to minimize the
      adverse effects of low health literacy on health and health outcomes, efforts
      should be invested in identifying and addressing the health needs of adults with
      low and marginal health literacy, especially in underserved areas such as rural
      and remote settings, where access to health-related information is limited.

PMID- 24307168
TI  - [Politics in the fight against Malaria in Casamance, Senegal: public health
      activity in the context of conflict and decentralization].

PMID- 24307169
TI  - Reinstating higher order properties of a study list by retrieving a list item.
AB  - In two experiments, we looked at the role of higher order list properties in
      episodic recall. A probabilistic paired-associate paradigm was used in which each
      cue was repeatedly paired with two different targets. This paradigm permitted us
      to cue for a target that had been studied with that cue in the last list, or to
      cue for either of the two targets that had been repeatedly paired with that cue,
      although neither the cue nor either of its two targets had been studied in the
      last list. In Experiment 1, the higher order property was whether all of the
      targets in a given list were animal names or vegetable names. In Experiment 2,
      the higher order property was whether all of the pairs in a list were
      associatively related or unrelated. The assumption was that if participants were
      using these higher order properties when they retrieved a target that had been
      studied in the last list, they would also use these properties when recalling in
      response to a cue that had been studied in other lists but not in the most recent
      list. The results supported the use of both kinds of higher order properties in
      episodic access. They also showed that these higher order properties were
      reinstated by retrieving a target, and were then used in the next memory access
      operation. The questions of why the retrieval of a target would reinstate a
      higher order list property and how these very different higher order list
      properties aid in episodic access were also discussed. 

PMID- 24307170
TI  - Biochemical and structural insights into RNA binding by Ssh10b, a member of the
      highly conserved Sac10b protein family in Archaea.
AB  - Proteins of the Sac10b family are highly conserved in Archaea. Ssh10b, a member
      of the Sac10b family from the hyperthermophilic crenarchaeon Sulfolobus shibatae,
      binds to RNA in vivo. Here we show that binding by Ssh10b destabilizes RNA
      secondary structure. Structural analysis of Ssh10b in complex with a 25-bp RNA
      duplex containing local distortions reveals that Ssh10b binds the two RNA strands
      symmetrically as a tetramer with each dimer bound asymmetrically to a single RNA
      strand. Amino acid residues involved in double-stranded RNA binding are similar,
      but non-identical, to those in dsDNA binding. The dimer-dimer interaction
      mediated by the intermolecular beta-sheet appears to facilitate the
      destabilization of base pairing in the secondary structure of RNA. Our results
      suggest that proteins of the Sac10b family may play important roles in RNA
      transactions requiring destabilization of RNA secondary structure in Sulfolobus. 

PMID- 24307171
TI  - Functional properties of the retinal glutamate transporters GLT-1c and EAAT5.
AB  - In the mammalian retina, glutamate uptake is mediated by members of a family of
      glutamate transporters known as "excitatory amino acid transporters (EAATs)."
      Here we cloned and functionally characterized two retinal EAATs from mouse, the
      GLT-1/EAAT2 splice variant GLT-1c, and EAAT5. EAATs are glutamate transporters
      and anion-selective ion channels, and we used heterologous expression in
      mammalian cells, patch-clamp recordings and noise analysis to study and compare
      glutamate transport and anion channel properties of both EAAT isoforms. We found
      GLT-1c to be an effective glutamate transporter with high affinity for Na(+) and
      glutamate that resembles original GLT-1/EAAT2 in all tested functional aspects.
      EAAT5 exhibits glutamate transport rates too low to be accurately measured in our
      experimental system, with significantly lower affinities for Na(+) and glutamate
      than GLT-1c. Non-stationary noise analysis demonstrated that GLT-1c and EAAT5
      also differ in single-channel current amplitudes of associated anion channels.
      Unitary current amplitudes of EAAT5 anion channels turned out to be approximately
      twice as high as single-channel amplitudes of GLT-1c. Moreover, at negative
      potentials open probabilities of EAAT5 anion channels were much larger than for
      GLT-1c. Our data illustrate unique functional properties of EAAT5, being a low
      affinity and low-capacity glutamate transport system, with an anion channel
      optimized for anion conduction in the negative voltage range. 

PMID- 24307172
TI  - Enhancement of TWIK-related acid-sensitive potassium channel 3 (TASK3) two-pore
      domain potassium channel activity by tumor necrosis factor alpha.
AB  - TASK3 two-pore domain potassium (K2P) channels are responsible for native leak K
      channels in many cell types which regulate cell resting membrane potential and
      excitability. In addition, TASK3 channels contribute to the regulation of
      cellular potassium homeostasis. Because TASK3 channels are important for cell
      viability, having putative roles in both neuronal apoptosis and oncogenesis, we
      sought to determine their behavior under inflammatory conditions by investigating
      the effect of TNFalpha on TASK3 channel current. TASK3 channels were expressed in
      tsA-201 cells, and the current through them was measured using whole cell voltage
      clamp recordings. We show that THP-1 human myeloid leukemia monocytes, co
      cultured with hTASK3-transfected tsA-201 cells, can be activated by the specific
      Toll-like receptor 7/8 activator, R848, to release TNFalpha that subsequently
      enhances hTASK3 current. Both hTASK3 and mTASK3 channel activity is increased by
      incubation with recombinant TNFalpha (10 ng/ml for 2-15 h), but other K2P
      channels (hTASK1, hTASK2, hTREK1, and hTRESK) are unaffected. This enhancement by
      TNFalpha is not due to alterations in levels of channel expression at the
      membrane but rather to an alteration in channel gating. The enhancement by
      TNFalpha can be blocked by extracellular acidification but persists for mutated
      TASK3 (H98A) channels that are no longer acid-sensitive even in an acidic
      extracellular environment. TNFalpha action on TASK3 channels is mediated through
      the intracellular C terminus of the channel. Furthermore, it occurs through the
      ASK1 pathway and is JNK- and p38-dependent. In combination, TNFalpha activation
      and TASK3 channel activity can promote cellular apoptosis. 

PMID- 24307173
TI  - Dissociated GalphaGTP and Gbetagamma protein subunits are the major activated
      form of heterotrimeric Gi/o proteins.
AB  - Although most heterotrimeric G proteins are thought to dissociate into Galpha and
      Gbetagamma subunits upon activation, the evidence in the Gi/o family has long
      been inconsistent and contradictory. The Gi/o protein family mediates inhibition
      of cAMP production and regulates the activity of ion channels. On the basis of
      experimental evidence, both heterotrimer dissociation and rearrangement have been
      postulated as crucial steps of Gi/o protein activation and signal transduction.
      We have now investigated the process of Gi/o activation in living cells directly
      by two-photon polarization microscopy and indirectly by observations of G protein
      coupled receptor kinase-derived polypeptides. Our observations of existing
      fluorescently labeled and non-modified Galphai/o constructs indicate that the
      molecular mechanism of Galphai/o activation is affected by the presence and
      localization of the fluorescent label. All investigated non-labeled, non-modified
      Gi/o complexes dissociate extensively upon activation. The dissociated subunits
      can activate downstream effectors and are thus likely to be the major activated
      Gi/o form. Constructs of Galphai/o subunits fluorescently labeled at the N
      terminus (GAP43-CFP-Galphai/o) seem to faithfully reproduce the behavior of the
      non-modified Galphai/o subunits. Galphai constructs labeled within the helical
      domain (Galphai-L91-YFP) largely do not dissociate upon activation, yet still
      activate downstream effectors, suggesting that the dissociation seen in non
      modified Galphai/o proteins is not required for downstream signaling. Our results
      appear to reconcile disparate published data and settle a long running dispute. 

PMID- 24307176
TI  - Greek version of the Internet Addiction Test: a validation study.
AB  - The aim of this project was to translate, culturally adapt and validate the
      Internet Addiction Test (IAT) in Greek adults. Twenty-one post-graduate medical
      students participated in the cultural adaptation procedure and 151 both post- and
      under-graduate medical students in the validation process. The internal
      consistency shown by a Cronbach's alpha was 0.91. Two-week test-retest
      reliability was rtt = 0.84, p < 0.001. Face validity was affirmed by 83.6 % of
      the students. In terms of convergent validity, the hours of daily internet use
      were positively correlated with IAT score (rho = 0.48, p < 0.001). Moreover, IAT
      scores were higher in students that reported use of online gambling (40.5 vs
      29.2, p = 0.004), pornographic sites (36.5 vs 28.0, p = 0.003) and online games
      (35.6 vs 28.2, p = 0.009). Exploratory factor analysis revealed three
      interpretable factors for the IAT, "Psychological/Emotional Conflict", "Time
      Management" and "Neglect Work", that showed good internal consistency and
      concurrent validity, explaining 55.3 % of the variance. The Greek version of IAT
      has shown good psychometric properties, comparable with the original IAT and the
      previously published translated versions, and can be a useful tool in future
      studies on internet addiction. 

PMID- 24307177
TI  - A recovery-oriented approach for an acute psychiatric ward: is it feasible and
      how does it affect staff satisfaction?
AB  - To evaluate professionals' attitudes to recovery and coercion, as well their
      satisfaction with working conditions before and after the implementation of a
      recovery-oriented ward concept on an admission ward. Longitudinal study design
      with two measurement times of the study sample, with a control group assessed at
      study end. Evaluating the implementation of the recovery concept, attitudes
      towards recovery, coercion, perceptions of the ward and working satisfaction were
      assessed with questionnaires and computed using Chi square and ANOVA variance
      analyses. The members of the intervention ward (n = 17) did not differ from the
      control group (n = 21), except that control group members were younger. The
      recovery-orientation of the study ward (ROSE questionnaire) increased
      significantly (alpha level = 0.05) from study begin to study end (p = 0.003), and
      compared to the control group (p = 0.002). The attitudes towards coercion did not
      change significantly in the intervention group, but did so compared to the
      control group. The contentedness (GMI) and the satisfaction with working
      conditions (ABB) of the intervention group members compared to control group was
      significantly higher (GMI: p = 0.004, ABB subscale working conditions: p = 0.043,
      satisfaction: p = 0.023). The study indicates that recovery-oriented principles
      can be implemented even in an acute admission ward, increasing team satisfaction
      with work, while attitudes towards coercion did not change significantly within
      this single-unit project. 

PMID- 24307175
TI  - Probing the dynamic distribution of bound states for methylcytosine-binding
      domains on DNA.
AB  - Although highly homologous to other methylcytosine-binding domain (MBD) proteins,
      MBD3 does not selectively bind methylated DNA, and thus the functional role of
      MBD3 remains in question. To explore the structural basis of its binding
      properties and potential function, we characterized the solution structure and
      binding distribution of the MBD3 MBD on hydroxymethylated, methylated, and
      unmethylated DNA. The overall fold of this domain is very similar to other MBDs,
      yet a key loop involved in DNA binding is more disordered than previously
      observed. Specific recognition of methylated DNA constrains the structure of this
      loop and results in large chemical shift changes in NMR spectra. Based on these
      spectral changes, we show that MBD3 preferentially localizes to methylated and,
      to a lesser degree, unmethylated cytosine-guanosine dinucleotides (CpGs), yet
      does not distinguish between hydroxymethylated and unmethylated sites. Measuring
      residual dipolar couplings for the different bound states clearly shows that the
      MBD3 structure does not change between methylation-specific and nonspecific
      binding modes. Furthermore, residual dipolar couplings measured for MBD3 bound to
      methylated DNA can be described by a linear combination of those for the
      methylation and nonspecific binding modes, confirming the preferential
      localization to methylated sites. The highly homologous MBD2 protein shows
      similar but much stronger localization to methylated as well as unmethylated
      CpGs. Together, these data establish the structural basis for the relative
      distribution of MBD2 and MBD3 on genomic DNA and their observed occupancy at
      active and inactive CpG-rich promoters. 

PMID- 24307174
TI  - Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-kappaB
      signaling pathway and proinflammatory response in human pericytes.
AB  - Pericytes and mesenchymal stem cells (MSCs) are ontogenically related, and in
      fact, no significant phenotypic differences could be observed by flow cytometry.
      Transcriptome analysis of human pericytes and MSCs revealed that 43 genes were up
      regulated more than 10-fold in pericytes compared with MSCs. Identification of
      Toll-like receptor 4 (TLR4) as one of the most abundant RNA species in pericytes
      with respect to MSCs and confirmation of TLR4 expression on the cell surface led
      us to obtain a comprehensive overview of the expression program of
      lipopolysaccharide (LPS)-stimulated pericytes. Transcriptional profiling of LPS
      treated cells revealed that 22 genes were up-regulated more than 5-fold. Of them,
      10 genes encoded chemokines and cytokines (CXCL10, CCL20, IL8, CXCL1, IL6, CCL2,
      IL1B, CXCL2, IL1A, and CXCL6), and three genes encoded adhesion molecules (ICAM1,
      VCAM1, and SELE). LPS induced nuclear translocation of the transcription factor
      NF-kappaB in stimulated pericytes. Moreover, inhibition of NF-kappaB activation
      by SC-514 blocked LPS-induced up-regulation of a subset of chemokine genes,
      confirming the key role of NF-kappaB in LPS signaling in pericytes. At the
      protein level, we assessed the secretion of the proinflammatory cytokines and
      chemokines IL-6, IL-8, CXCL1, CXCL2, CXCL3, and CCL2 not only after LPS treatment
      but also in HMGB1-stimulated pericytes. Up-regulation of the adhesion molecules
      ICAM-1 and VCAM-1 resulted in an increased adhesion of peripheral blood
      leukocytes to an LPS-treated pericyte monolayer. The role of pericytes in the
      inflammatory context has been scarcely addressed; according to these results,
      pericytes should be considered as active players in the inflammatory cascade with
      potential physiopathological implications. 

PMID- 24307178
TI  - Internet psychoeducation for bipolar affective disorder: basis for preparation
      and first experiences.
AB  - There is growing evidence that patients with bipolar affective disorder (BAD),
      who use medication, respond well to further psychotherapeutic interventions.
      Internet-based psychoeducation is typically centered on the interaction between a
      client and therapist via the Internet. Multiple methods were required to
      investigate existing psychoeducational and psychotherapeutic strategies used on
      patients suffering from BAD. Systematic reviews and original reports of all
      trials of psychoeducation in BAD patients were retrieved. Patients with BAD, who
      were hospitalized in a psychiatric department or attended a day hospital program,
      were exposed to the first version of the program during the treatment, and then
      questioned about understandability, comprehensibility, and usefulness of each
      lecture. Twelve modules of the Internet E-Program for BAD were developed and the
      intervention was a pilot tested with twelve patients. Internet psychoeducation
      program for BAD is an intervention designed for universal implementation that
      addresses heightened learning needs of patients suffering from BAD. It is
      designed to promote confidence and reduce the number of episodes of the disorder
      by providing skills in monitoring warning signs, planning daily activities and
      practicing communication skills. 

PMID- 24307179
TI  - Factors and processes modulating phenotypes in neuronopathic lysosomal storage
      diseases.
AB  - Lysosomal storage diseases are inherited metabolic disorders caused by genetic
      defects causing deficiency of various lysosomal proteins, and resultant
      accumulation of non-degraded compounds. They are multisystemic diseases, and in
      most of them (>70%) severe brain dysfunctions are evident. However, expression of
      various phenotypes in particular diseases is extremely variable, from non
      neuronopathic to severely neurodegenerative in the deficiency of the same enzyme.
      Although all lysosomal storage diseases are monogenic, clear genotype-phenotype
      correlations occur only in some cases. In this article, we present an overview on
      various factors and processes, both general and specific for certain disorders,
      that can significantly modulate expression of phenotypes in these diseases. On
      the basis of recent reports describing studies on both animal models and clinical
      data, we propose a hypothesis that efficiency of production of compounds that
      cannot be degraded due to enzyme deficiency might be especially important in
      modulation of phenotypes of patients suffering from lysosomal storage diseases.

PMID- 24307180
TI  - Alcohol-induced psychotic disorder: a review.
AB  - While alcohol-induced psychotic disorder (AIPD) is well recognised, relatively
      little is known about the condition. We undertook a review of the literature to
      identify studies on the epidemiology, clinical manifestations, underlying
      neurobiology and treatment of AIPD. Few prospective studies have been conducted
      on AIPD. Recent advances have focussed on epidemiological, phenomenological,
      neuro-imaging, treatment and outcome issues. Current evidence suggests AIPD can
      be clinically distinguished from alcohol-withdrawal delirium and schizophrenia.
      The disorder may be more common than previously recognised depending on the
      inclusion criteria applied. AIPD is associated with high co-morbidity with other
      psychiatric disorders, high re-hospitalization and mortality rates and suicidal
      behaviour. Concurrent dysregulation of several neurotransmitter systems may be
      involved in the pathogenesis of hallucinations in alcohol dependence, and neuro
      imaging studies suggest perfusion abnormalities to various brain regions.
      Antipsychotic treatment remains the preferred treatment for AIPD. The prognosis
      appears less favourable than previously believed, yet usually good when
      abstinence can be maintained. 

PMID- 24307182
TI  - Intra- and interobserver agreement with regard to describing adnexal masses using
      International Ovarian Tumor Analysis terminology: reproducibility study involving
      seven observers.
AB  - OBJECTIVES: To estimate intraobserver repeatability and interobserver agreement
      in assessing the presence of papillary projections in adnexal masses and in
      classifying adnexal masses using the International Ovarian Tumor Analysis
      terminology for ultrasound examiners with different levels of experience. We also
      aimed to identify ultrasound findings that cause confusion and might be
      interpreted differently by different observers, and to determine if repeatability
      and agreement change after consensus has been reached on how to interpret
      'problematic' ultrasound images. METHODS: Digital clips (two to eight clips per
      adnexal mass) with gray-scale and color/power Doppler information of 83 adnexal
      masses in 80 patients were evaluated independently four times, twice before and
      twice after a consensus meeting, by four experienced and three less experienced
      ultrasound observers. The variables analyzed were tumor type (unilocular,
      unilocular solid, multilocular, multilocular solid, solid) and presence of
      papillary projections. Intraobserver repeatability was evaluated for each
      observer (percentage agreement, Cohen's kappa). Interobserver agreement was
      estimated for all seven observers (percentage agreement, Fleiss kappa, Cohen's
      kappa). RESULTS: There was uncertainty about how to define a solid component and
      a papillary projection, but consensus was reached at the consensus meeting.
      Interobserver agreement for tumor type was good both before and after the
      consensus meeting, with no clear improvement after the meeting, mean percentage
      agreement being 76.0% (Fleiss kappa, 0.695) before the meeting and 75.4% (Fleiss
      kappa, 0.682) after the meeting. Interobserver agreement with regard to papillary
      projections was moderate both before and after the consensus meeting, with no
      clear improvement after the meeting, mean percentage agreement being 86.6%
      (Fleiss kappa, 0.536) before the meeting and 82.7% (Fleiss kappa, 0.487) after
      it. There was substantial variability in pairwise agreement for papillary
      projections (Cohen's kappa, 0.148-0.787). Intraobserver repeatability with regard
      to tumor type was very good and similar before and after the consensus meeting
      (agreement 87-95%, kappa, 0.83-0.94). With regard to papillary projections
      intraobserver repeatability was good or very good both before and after the
      consensus meeting (agreement 88-100%, kappa, 0.64-1.0). CONCLUSIONS: Despite
      uncertainty about how to define solid components, interobserver agreement was
      good for tumor type. The interobserver agreement for papillary projection was
      moderate but very variable between observer pairs. The term 'papillary
      projection' might need a more precise definition. The consensus meeting did not
      change inter- or intraobserver agreement.

PMID- 24307181
TI  - Rats with minimal hepatic encephalopathy due to portacaval shunt show
      differential increase of translocator protein (18 kDa) binding in different brain
      areas, which is not affected by chronic MAP-kinase p38 inhibition.
AB  - Neuroinflammation plays a main role in neurological deficits in rats with minimal
      hepatic encephalopathy (MHE) due to portacaval shunt (PCS). Treating PCS rats
      with SB239063, an inhibitor of MAP-kinase-p38, reduces microglial activation and
      brain inflammatory markers and restores cognitive and motor function. The
      translocator protein-(18-kDa) (TSPO) is considered a biomarker of
      neuroinflammation. TSPO is increased in brain of PCS rats and of cirrhotic
      patients that died in hepatic coma. Rats with MHE show strong microglial
      activation in cerebellum and milder in other areas when assessed by MHC-II
      immunohistochemistry. This work aims were assessing: 1) whether binding of TSPO
      ligands is selectively increased in cerebellum in PCS rats; 2) whether treatment
      with SB239063 reduces binding of TSPO ligands in PCS rats; 3) which cell type
      (microglia, astrocytes) increases TSPO expression. Quantitative autoradiography
      was used to assess TSPO-selective (3)H-(R)-PK11195 binding to different brain
      areas. TSPO expression increased differentially in PCS rats, reaching mild
      expression in striatum or thalamus and very high levels in cerebellum. TSPO was
      expressed in astrocytes and microglia. Treatment with SB239063 did not reduces
      (3)[H]-PK11195 binding in PCS rats. SB239063 reduces microglial activation and
      levels of inflammatory markers, but not binding of TSPO ligands. This indicates
      that SB239063-induced neuroinflammation reduction in PCS rats is not mediated by
      effects on TSPO. Also, enhanced TSPO expression is not always associated with
      cognitive or motor deficits. If enhanced TSPO expression plays a role in
      mechanisms leading to neurological alterations in MHE, SB239063 would interfere
      these mechanisms at a later step. 

PMID- 24307183
TI  - An association between external hydrocephalus in infants and reversible collapse
      of the venous sinuses.
AB  - The etiology of external hydrocephalus is usually ascribed to either a delay in
      maturation or obstruction of the arachnoid granulations, but the arachnoid
      granulations are absent in neonates. Venous outflow stenoses, similar to those
      seen in idiopathic intracranial hypertension (IIH), have been described in
      external hydrocephalus. A reversible collapse of the sinuses is known to operate
      in IIH, but collapsible sinuses have not been previously described in infants
      with external hydrocephalus. Three infants with external hydrocephalus had
      magnetic resonance venography at differing time points during their illness. The
      venous sinuses varied in size depending on the cerebrospinal fluid pressure
      similar to IIH in adults. External hydrocephalus may be analogous to IIH in
      adults. 

PMID- 24307185
TI  - Enhancement of survival of alginate-encapsulated Lactobacillus casei NCDC 298.
AB  - BACKGROUND: Micro-encapsulation of hydrocolloids improves the survival of
      sensitive probiotic bacteria in the harsh conditions that prevail in foods and
      during gastrointestinal passage by segregating them from environments.
      Incorporation of additives in encapsulating hydrocolloids and coatings of
      microcapsules further improves the survival of the probiotics. In this study, the
      effect of incorporation of resistant-maize starch in alginate for micro
      encapsulation and coating of microcapsules with poly-l-lysine, stearic acid and
      bees wax on the survival of encapsulated Lactobacillus casei NCDC 298 at pH 1.5,
      2% high bile salt, 65  degrees C for 20 min and release of viable lactobacilli
      cells from the capsule matrix in simulated aqueous solutions of colonic pH were
      assessed. RESULTS: Addition of resistant maize starch (2%) improved the survival
      of encapsulated L. casei NCDC 298. Coating of microcapsules with poly-L-lysine
      did not further improve the protection of encapsulated cells from the harsh
      conditions; however, bees wax and stearic acid (2%) improved the survival under
      similar conditions. Incorporation of maize starch (2%) in alginate followed by
      coating of beads with stearic acid (2%) led to better protection and complete
      release of entrapped lactobacilli in simulated colonic pH solution was observed.
      CONCLUSION: Additional treatments improve the survival of alginate-encapsulated
      lactobacilli cells without hindering the release of active cells from the capsule
      matrix and hence, the resulting encapsulated probiotics can be exploited in the
      development of probiotic functional foods with better survival of sensitive
      probiotic organisms.

PMID- 24307186
TI  - Mechanisms of resistance to paraquat in plants.
AB  - The aim of this brief review is to draw information from studies of the mechanism
      of evolved resistance in weeds, together with information from laboratory studies
      of paraquat tolerance in model plants. Plants having mutations that limit
      paraquat uptake into cytoplasm, that confer various stress tolerances or that
      have transgenes that co-express two or more of the chloroplast Halliwell-Asada
      cycle enzymes can all exhibit enhanced tolerance to paraquat. However, none of
      these mechanisms correspond to the high-level resistances that have evolved
      naturally in weeds. Most, but not all, of the evidence from studies of paraquat
      resistant biotypes of weeds can reasonably be reconciled with the proposal of a
      single major gene mechanism that sequesters paraquat away from chloroplasts and
      into the vacuole. However, the molecular details of this putative mechanism
      remain ill-defined.

PMID- 24307187
TI  - Proteomic analysis of outer membrane vesicles from the probiotic strain
      Escherichia coli Nissle 1917.
AB  - Escherichia coli Nissle 1917 (EcN) is a probiotic used for the treatment of
      intestinal disorders. EcN improves gastrointestinal homeostasis and microbiota
      balance; however, little is known about how this probiotic delivers effector
      molecules to the host. Outer membrane vesicles (OMVs) are constitutively produced
      by Gram-negative bacteria and have a relevant role in bacteria-host interactions.
      Using 1D SDS-PAGE and highly sensitive LC-MS/MS analysis we identified in this
      study 192 EcN vesicular proteins with high confidence in three independent
      biological replicates. Of these proteins, 18 were encoded by strain-linked genes
      and 57 were common to pathogen-derived OMVs. These proteins may contribute to the
      ability of this probiotic to colonize the human gut as they fulfil functions
      related to adhesion, immune modulation or bacterial survival in host niches. This
      study describes the first global OMV proteome of a probiotic strain and provides
      evidence that probiotic-derived OMVs contain proteins that can target these
      vesicles to the host and mediate their beneficial effects on intestinal function.
      All MS data have been deposited in the ProteomeXchange with identifier PXD000367
      (http://proteomecentral.proteomexchange.org/dataset/PXD000367). 

PMID- 24307188
TI  - Enough.

PMID- 24307184
TI  - Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD
      study.
AB  - OBJECTIVE: To evaluate 8-year weight losses achieved with intensive lifestyle
      intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study.
      DESIGN AND METHODS: Look AHEAD assessed the effects of intentional weight loss on
      cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type
      2 diabetes, randomly assigned to ILI or usual care (i.e., diabetes support and
      education [DSE]). The ILI provided comprehensive behavioral weight loss
      counseling over 8 years; DSE participants received periodic group education only.
      RESULTS: All participants had the opportunity to complete 8 years of intervention
      before Look AHEAD was halted in September 2012; >=88% of both groups completed
      the 8-year outcomes assessment. ILI and DSE participants lost (mean +/- SE) 4.7%
      +/- 0.2% and 2.1 +/- 0.2% of initial weight, respectively (P < 0.001) at year 8;
      50.3% and 35.7%, respectively, lost >=5% (P < 0.001), and 26.9% and 17.2%,
      respectively, lost >=10% (P < 0.001). Across the 8 years ILI participants,
      compared with DSE, reported greater practice of several key weight-control
      behaviors. These behaviors also distinguished ILI participants who lost >=10% and
      kept it off from those who lost but regained. CONCLUSIONS: Look AHEAD's ILI
      produced clinically meaningful weight loss (>=5%) at year 8 in 50% of patients
      with type 2 diabetes and can be used to manage other obesity-related co-morbid
      conditions.

PMID- 24307189
TI  - Transference as a religious phenomenon in psychotherapy.
AB  - An analysis is presented of the conventional and far-reaching existential
      interpretations of the concept of transference. Analogies are drawn between the
      deepest meanings of transference and interpersonal and religious (man-and-God)
      dialogue. By way of case illustrations, it is shown that transference from
      patient to therapist can have implications for the patient's real relationship
      with God. 

PMID- 24307190
TI  - Religious issues in psychotherapy.
AB  - Religious belief is important to a large proportion of our population. It has
      been found to be a potent neutralizer of death anxiety. Religion and
      psychotherapy shave values relating to self-actualization. It is the
      responsibility of psychotherapists to be aware of their own ambivalences and
      biases; to assess the significance of religious belief in the lives of their
      clients; to clarify conflicting views and values of client and therapist; to
      treat the client's psychodynamic problems; and respectfully to refer spiritual
      problems outside the domain of psychotherapy to the client's minister. An
      illustrative example from the author's practice is included. 

PMID- 24307191
TI  - Spiritual support for caregivers of dementia patients.
AB  - Dementia is considered the "major psychiatric disorder of old age" and affects
      over 4 million people in the United States. As Alzheimer's disease and other
      dementias progress, the patient can become increasingly dependent on the family
      for care. This dependency can place the caregiver in a role that is both
      difficult and demanding. In this study coping strategies used by family
      caregivers of dementia patients and caregivers' sense of burden were assessed.
      Burden scores were significantly correlated with spiritual support, an external
      coping strategy. When spiritual well-being is integrated with medical and
      psychosocial needs, the clergy and spiritual community can play an integral role
      in the care for families and dementia patients. 

PMID- 24307192
TI  - The value of confession and forgiveness according to Jung.
AB  - This article represents a broad survey of the views of C. G. Jung regarding
      confession and for giveness. Man, a naturally religious being, has a need to
      confess his wrong and to gain forgiveness of one sanctioned to absolve. The
      curative effect of confession has been known for centuries. Without confession,
      man remains in moral isolation. Priests, ministers, and rabbis, as well as
      psychotherapists, attest to the universality of this human phenomenon. Confession
      is located in that place where psychology and religion meet-guilt. Jung's views
      on confession bridge the chasm between psychology and religion. 

PMID- 24307193
TI  - Psychiatry and religion: Judeo-Christian theism and Fromm's humanism.
AB  - This paper provides a discussion of the ethical humanism of the late
      psychoanalyst Eric Fromm as compared to traditional Judeo-Christian theism.
      Considering their respective views of human nature and possibility, and of the
      relationship between truth, reason, and revelation, the authors posit that Fromm
      and traditional theists take radically different positions, making their
      religious stances fundamentally incompatible. In conclusion, the authors suggest
      how these differences could have significant implication for pastoral care. 

PMID- 24307194
TI  - Religion and health in Mexican Americans.
AB  - The relationship between religion and health was investigated using data from a
      three-generation study of mexican Americans. Two measures of religion-religious
      institution attendance and self-rated religiosity-were correlated with a number
      of functional health indicators, including self-rated health, activity
      restriction owing to health, bed disability days, physician utilization, worry
      over health, a physical symptoms scale, and a depression scale. In addition,
      prevalence rates were calculated for several major chronic diseases. Many
      significant associations obtained, as well as an inverse relationship between
      self-rated religiosity and hypertension. These findings are interpreted in light
      of the literature on religious attendance and health and on religion and aging. 

PMID- 24307195
TI  - Religion and aging.
AB  - Life history data and cultural values are used to suggest ways in which personal
      and social beliefs influence the quality of experiences of aging. Central
      questions are the extent to which an individual can select beliefs that lead to a
      longer, more meaningful life and the special influence that religion may have in
      enhancing aging. Responsiveness to needs of the elderly is a necessary component
      of enlightened planning for the future. Secularization and industrialization have
      diminished roles and expectations for the elderly. Religion may be an effective
      means to identify these concerns and improve the quality of life of older people.

PMID- 24307196
TI  - The hospice: Humane care for the dying.
AB  - The hospice movement arose as a reaction to the dehumanizing atmosphere of acute
      care hospitals, where excessive utilization of life support equipment deprived
      dying patients of a meaningful vision of their destiny. Respecting the spiritual
      quest of the terminally ill for wholeness and dignity, the hospice concept
      prescribes the rendering of compassionate and pastoral care by a benevolent
      community of family, health care staff, friends, and clergy. Approximately 800
      hospice programs are currently evolving in the United States. St. Mary's
      (formerly "Hillhaven") Hospice in Tucson, Arizona, offers the most comprehensive
      program of services, including home care, inpatient care, and artistic media
      through which the dying express their creativity. Numerous demonstration projects
      funded by several government agencies, principally the Health Care Financing
      Administration (HCFA), are expected to result in legislative actions eliminating
      barriers to reimbursement of the cost of hospice services by Medicare, Medicaid,
      and other third-party payers. Existential analysis reveals the value of religion
      and spiritual support in enabling the dying to banish anxiety and muster the hope
      requisite for fully appreciating the authentic meaning of their destiny. 

PMID- 24307197
TI  - The mediating roles of cancer-related rumination in the relationship between
      dispositional hope and psychological outcomes among childhood cancer survivors.
AB  - OBJECTIVE: This study aimed to examine the effects of dispositional hope on
      psychopathology as well as self-perceived positive change in childhood cancer
      survivors through the potential mediation of cancer-related ruminations. METHODS:
      A cross-sectional design was used, and a group of childhood cancer survivors (N =
      89; mean age = 23.2 years; age range = 17.2-31.3 years) were studied.
      Dispositional hope level was measured by the Hope Scale; positive and negative
      cancer-related ruminations were assessed by the Chinese Cancer-related Rumination
      Scale; depression symptoms were measured by Beck Depression Inventory; and
      anxiety symptoms were measured by Beck Anxiety Inventory. Positive adjustment
      outcome of posttraumatic growth (PTG) was assessed by the Chinese Post-traumatic
      Growth Inventory. Multiple regressions were used to analyze the relationship
      between dispositional hope and the outcome variables of PTG, anxiety and
      depression and the potential mediators of positive and negative cancer-related
      rumination. RESULTS: Dispositional hope was positively related to PTG, and the
      correlation was specifically mediated by positive cancer-related rumination.
      Dispositional hope also correlated with lower levels of depression and anxiety,
      specifically mediated by negative cancer-related rumination. CONCLUSION: The
      present finding supported hope as a significant positive factor for childhood
      cancer survivors, which was associated with PTG and better psychological
      adjustment. The findings may inform development of therapeutic intervention
      programs aimed at increasing childhood cancer patients' hope levels, which may be
      correlated with more positive cancer-related thoughts and better adjustment. The
      present study, which examined survivors diagnosed at young age, may enrich
      existing studies on the effect of onset age and adjustment outcomes.

PMID- 24307198
TI  - Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine.
AB  - Ibogaine is a psychoactive indole alkaloid. Its use as an antiaddictive agent has
      been accompanied by QT prolongation and cardiac arrhythmias, which are most
      likely caused by human ether a go-go-related gene (hERG) potassium channel
      inhibition. Therefore, we studied in detail the interaction of ibogaine with hERG
      channels heterologously expressed in mammalian kidney tsA-201 cells. Currents
      through hERG channels were blocked regardless of whether ibogaine was applied via
      the extracellular or intracellular solution. The extent of inhibition was
      determined by the relative pH values. Block occurred during activation of the
      channels and was not observed for resting channels. With increasing
      depolarizations, ibogaine block grew and developed faster. Steady-state
      activation and inactivation of the channel were shifted to more negative
      potentials. Deactivation was slowed, whereas inactivation was accelerated.
      Mutations in the binding site reported for other hERG channel blockers (Y652A and
      F656A) reduced the potency of ibogaine, whereas an inactivation-deficient double
      mutant (G628C/S631C) was as sensitive as wild-type channels. Molecular drug
      docking indicated binding within the inner cavity of the channel independently of
      the protonation of ibogaine. Experimental current traces were fit to a kinetic
      model of hERG channel gating, revealing preferential binding of ibogaine to the
      open and inactivated state. Taken together, these findings show that ibogaine
      blocks hERG channels from the cytosolic side either in its charged form alone or
      in company with its uncharged form and alters the currents by changing the
      relative contribution of channel states over time. 

PMID- 24307199
TI  - Regulation of death induction and chemosensitizing action of 3-bromopyruvate in
      myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase
      activity modulation.
AB  - 3-Bromopyruvate (3-BrP) is an alkylating, energy-depleting drug that is of
      interest in antitumor therapies, although the mechanisms underlying its
      cytotoxicity are ill-defined. We show here that 3-BrP causes concentration
      dependent cell death of HL60 and other human myeloid leukemia cells, inducing
      both apoptosis and necrosis at 20-30 MUM and a pure necrotic response at 60 MUM.
      Low concentrations of 3-BrP (10-20 MUM) brought about a rapid inhibition of
      glycolysis, which at higher concentrations was followed by the inhibition of
      mitochondrial respiration. The combination of these effects causes concentration
      dependent ATP depletion, although this cannot explain the lethality at
      intermediate 3-BrP concentrations (20-30 MUM). The oxidative stress caused by
      exposure to 3-BrP was evident as a moderate overproduction of reactive oxygen
      species and a concentration-dependent depletion of glutathione, which was an
      important determinant of 3-BrP toxicity. In addition, 3-BrP caused glutathione
      dependent stimulation of p38 mitogen-activated protein kinase (MAPK), mitogen
      induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK),
      and protein kinase B (Akt)/mammalian target of rapamycin/p70S6K phosphorylation
      or activation, as well as rapid LKB-1/AMP kinase (AMPK) activation, which was
      later followed by Akt-mediated inactivation. Experiments with pharmacological
      inhibitors revealed that p38 MAPK activation enhances 3-BrP toxicity, which is
      conversely restrained by ERK and Akt activity. Finally, 3-BrP was seen to
      cooperate with antitumor agents like arsenic trioxide and curcumin in causing
      cell death, a response apparently mediated by both the generation of oxidative
      stress induced by 3-BrP and the attenuation of Akt and ERK activation by
      curcumin. In summary, 3-BrP cytotoxicity is the result of several combined
      regulatory mechanisms that might represent important targets to improve
      therapeutic efficacy. 

PMID- 24307200
TI  - Maintained cocaine self-administration is determined by quantal responses:
      implications for the measurement of antagonist potency.
AB  - The change in frequency of cocaine self-administration as a function of the unit
      dose is widely assumed to represent a graded pharmacodynamic response.
      Alternatively, a pharmacological theory states that during maintained self
      administration, a quantal response occurs at a minimum maintained cocaine
      concentration (satiety threshold). Rats self-administered cocaine at unit doses
      spanning an 8-fold range from 0.75 to 6 umol/kg. Despite an approximately 7-fold
      difference in the interinjection intervals, there were no differences in the
      plasma cocaine concentration at the time of lever press across this range of unit
      doses, consistent with the satiety threshold representing an equiactive cocaine
      concentration. Because self-administration always occurs when cocaine
      concentrations decline back to the satiety threshold, this behavior represents a
      process of automatic back titration of equiactive agonist concentrations.
      Therefore, the lower frequency of self-administration at higher unit doses is
      caused by an increase in the duration of the cocaine-induced satiety response,
      and the graded dose-frequency relationship is due to cocaine pharmacokinetics.
      After the interinjection intervals at a particular unit dose were stable, rats
      were injected with the competitive D1-like dopamine receptor antagonist R-(+)-7
      chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390;
      15 nmol/kg intravenously) and the session continued. At all cocaine unit doses,
      SCH23390 accelerated self-administration with a concomitant increase in the
      calculated satiety threshold, and these equiactive cocaine concentration ratios
      were independent of the cocaine unit dose. Therefore, the measurement of
      antagonist potency requires only a single unit dose of cocaine, selected on the
      basis of convenience, and using multiple cocaine unit doses is redundant.

PMID- 24307201
TI  - Antinociceptive effects of central administration of the endogenous cannabinoid
      receptor type 1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(alpha)], an N
      terminally extended hemopressin peptide.
AB  - The cannabinoid system has been demonstrated to modulate the acute and chronic
      pain of multiple origins. Mouse VD-hemopressin(alpha) [(m)VD-Hpalpha], an 11
      residue alpha-hemoglobin-derived peptide, was recently reported to function as a
      selective agonist of the cannabinoid receptor type 1 (CB1) in vitro. To
      characterize its behavioral and physiological properties, we investigated the in
      vivo effects of (m)VD-Hpalpha in mice. In the mouse tail-flick test, (m)VD
      Hpalpha dose-dependently induced antinociception after supraspinal (EC50 = 6.69
      nmol) and spinal (EC50 = 2.88 nmol) administration. The antinociceptive effects
      of (m)VD-Hpalpha (intracerebroventricularly and intrathecally) were completely
      blocked by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H
      pyrazole-3- carboxamide (AM251; CB1 antagonist), but not by 6-iodo-2-methyl-1-[2
      (4-morpholinyl)ethyl]-1H-indol-3-yl(4-methoxyphenyl)-methanone (AM630; CB2
      antagonist) or naloxone (opioid antagonist), showing its selectivity to the CB1
      receptor. Furthermore, the central nervous system (CNS) effects of (m)VD-Hpalpha
      were evaluated in body temperature, locomotor activity, tolerance development,
      reward, and food intake assays. At the highly antinociceptive dose (3 * EC50),
      (m)VD-Hpalpha markedly exerted hypothermia and hypoactivity after supraspinal
      administration. Repeated intracerebroventricular injection of (m)VD-Hpalpha
      resulted in both development of tolerance to antinociception and conditioned
      place aversion. In addition, central injection of (m)VD-Hpalpha dose-dependently
      stimulated food consumption. These findings demonstrate that this novel
      cannabinoid peptide agonist induces CB1-mediated central antinociception with
      some CNS effects, which further supports a CB1 agonist character of (m)VD
      Hpalpha. Moreover, the current study will be helpful to understand the in vivo
      properties of the endogenous peptide agonist of the cannabinoid CB1 receptor.

PMID- 24307202
TI  - Bronchoprotection by olodaterol is synergistically enhanced by tiotropium in a
      guinea pig model of allergic asthma.
AB  - The novel once-daily beta2-agonist bronchodilator drug olodaterol has recently
      been shown to be effective in patients with allergic asthma for >24 hours. An
      increased cholinergic tone common to these patients may decrease the
      effectiveness of beta2-agonists. This could provide a rationale for combination
      therapy with olodaterol and the long-acting anticholinergic tiotropium to aim for
      a once-daily treatment regimen. In guinea pigs, we evaluated the protective
      effects of olodaterol, alone and in combination with tiotropium, on airway
      responsiveness to histamine, which is partially mediated by a cholinergic reflex
      mechanism. In addition, using a guinea pig model of acute allergic asthma, we
      examined the cooperative effects of these bronchodilators on allergen-induced
      early (EAR) and late (LAR) asthmatic reactions, airway hyper-responsiveness (AHR)
      to histamine, and airway inflammation. It was demonstrated that the protective
      effect of olodaterol against histamine-induced bronchoconstriction was
      synergistically enhanced and prolonged in the presence of tiotropium. In
      addition, tiotropium synergistically augmented both the reversal of and the
      protection against the allergen-induced AHR after the EAR by olodaterol.
      Olodaterol and tiotropium were highly effective in inhibiting the magnitude of
      the allergen-induced EAR and LAR, and both reactions were fully inhibited by the
      combination of these drugs. It is remarkable that these effects were not
      associated with an effect on inflammatory cell infiltration in the airways. In
      conclusion, the results indicate that combination therapy with olodaterol and
      tiotropium may be highly effective in the treatment of allergen-induced asthmatic
      reactions and AHR.

PMID- 24307203
TI  - Reactive oxygen species-mediated DNA damage and apoptosis in human skin epidermal
      cells after exposure to nickel nanoparticles.
AB  - Nickel nanoparticles (NiNPs) are increasingly used in various applications due to
      their unique properties. However, there is little information concerning the
      toxicity of NiNPs in the human skin cell (A431). The present study was designed
      to investigate the cytotoxicity, apoptosis, and DNA damage due to NiNPs in A431
      cells. A cellular proliferative capacity test showed that NiNPs induce
      significant cytotoxicity in a dose- and time-dependent manner. NiNPs were also
      found to induce oxidative stress evidenced by the generation of reactive oxygen
      species (ROS) and depletion of glutathione (GSH). Further, co-treatment with the
      antioxidant N-acetylcysteine (NAC) mitigated the ROS generation due to NiNPs,
      suggesting the potential mechanism of oxidative stress. NiNPs also induced
      significant elevation of lipid peroxidation, catalase, and superoxide dismutase
      and caspase-3 activity in A431 cells. In addition, NAC suppressed NiNP-induced
      caspase-3 activity. DNA fragmentation analysis using the comet assay showed that
      the NiNPs cause genotoxicity in a dose- and time-dependent manner. Therefore, the
      study points out the capability of the NiNPs to induce oxidative stress resulting
      in apoptosis and genotoxicity. This study warrants more careful assessment of
      NiNPs before their industrial applications. 

PMID- 24307204
TI  - Sample size determination for studies designed to estimate covariate-dependent
      reference quantile curves.
AB  - Accuracy and sample size issues concerning the estimation of covariate-dependent
      quantile curves are considered. It is proposed to measure the precision of an
      estimate of the pth quantile at a given covariate value by the probability with
      which this estimate lies between the p1 th and p2 th quantile, where p1  < p < p2
      . Requiring that this probability exceeds a given confidence bound for all
      covariate values in a specified range leads to a sample size criterion.
      Approximate formulae for the precision and sample size are derived for the normal
      parametric regression approach and for the semiparametric quantile regression
      method. A simulation study is performed to evaluate the accuracy of the
      approximations. Numerical evaluations show that rather large numbers of subjects
      are needed to construct quantile curves with a reasonable amount of accuracy,
      especially if the quantile regression method is applied.

PMID- 24307205
TI  - Enantioselective palladium(II) phosphate catalyzed three-component reactions of
      pyrrole, diazoesters, and imines.

PMID- 24307207
TI  - Therapeutic drug monitoring of zuclopenthixol in a double-blind placebo
      controlled discontinuation study in adults with intellectual disabilities and
      aggressive behaviour.
AB  - The trial was a double-blind, placebo-controlled comparison with a
      discontinuation design. 49 mentally retarded patients with aggressive behaviour
      were treated with zuclopenthixol at a dose of 2-20 mg/d. At each visit the
      clinical effect was evaluated. Correlations between dose, serum concentration,
      and efficacy measures were calculated. The mean dose was 10.0 mg/day (+/-5.17);
      the mean serum concentration 4.19 ng/mL (+/-3.16). Associations of dosage, serum
      concentration and clinical efficiency did not result in coherent patterns.
      Correlations with clinical efficiency measures appeared to be contradictory for
      dosage and serum concentrations, respectively. As no consistent associations
      between dosage, serum concentration, and clinical efficiency measures were found,
      different hypotheses explaining the results are discussed. 

PMID- 24307208
TI  - Strength of TCR signal from self-peptide modulates autoreactive thymocyte
      deletion and Foxp3(+) Treg-cell formation.
AB  - Autoreactive CD4(+) CD8(-) (CD4SP) thymocytes can be subjected to deletion when
      they encounter self-peptide during their development, but they can also undergo
      selection to become CD4SPFoxp3(+) Treg cells. We have analyzed the relationship
      between these distinct developmental fates using mice in which signals
      transmitted by the TCR have been attenuated by mutation of a critical tyrosine
      residue of the adapter protein SLP-76. In mice containing polyclonal TCR
      repertoires, the mutation caused increased frequencies of CD4SPFoxp3(+)
      thymocytes. CD4SP thymocytes expressing TCR Vbeta-chains that are subjected to
      deletion by endogenous retroviral superantigens were also present at increased
      frequencies, particularly among Foxp3(+) thymocytes. In transgenic mice in which
      CD4SP thymocytes expressing an autoreactive TCR undergo both deletion and Treg
      cell formation in response to a defined self-peptide, SLP-76 mutation abrogated
      deletion of autoreactive CD4SP thymocytes. Notably, Foxp3(+) Treg-cell formation
      still occurred, albeit with a reduced efficiency, and the mutation was also
      associated with decreased Nur77 expression by the autoreactive CD4SP thymocytes.
      These studies provide evidence that the strength of the TCR signal can play a
      direct role in directing the extent of both thymocyte deletion and Treg-cell
      differentiation, and suggest that distinct TCR signaling thresholds and/or
      pathways can promote CD4SP thymocyte deletion versus Treg-cell formation. 

PMID- 24307209
TI  - Lactate down-regulates matrix systhesis and promotes apoptosis and autophagy in
      rat nucleus pulposus cells.
AB  - The intervertebral disk (IVD) is avascular and anaerobic glycolysis has been
      recognized as the main source of energy. Due to anaerobic glycolysis, there are
      high levels of lactate production in disk. Previous study shows lactate
      concentration is elevated in the degenerated IVD. However, it is not clear how
      lactate causes degeneration of disks. In this study, we found that 2 mM lactate
      promote proliferation of NP cells, while 6 mM lactate slightly inhibit their
      proliferation. By detection under transmission electron microscopy, and western
      bolt for autophagy related protein beclin-1, LC3 and p62, we demonstrated that 6
      mM lactate leads to autophagy induction of NP cells. TUNEL results showed that
      the apoptosis incidence was increased. High lactate concentration induced the
      degradation in protein expression and mRNA level of GAG content, type II collagen
      and slight increase of type I collagen. Based on these observations, we conclude
      that high lactate concentration is a pathogenic factor for IVD degeneration, and
      lactate metabolism may be a new therapeutic target for IVD degeneration.

PMID- 24307210
TI  - Development, validity and reliability of the short multidimensional positive
      mental health instrument.
AB  - PURPOSE: The 47-item positive mental health (PMH) instrument measures the level
      of PMH in multiethnic adult Asian populations. This study aimed to (1) develop a
      short PMH instrument and (2) establish its validity and reliability among the
      adult Singapore population. METHODS: Two separate studies were conducted among
      adult community-dwelling Singapore residents of Chinese, Malay or Indian
      ethnicity where participants completed self-administered questionnaires. In the
      first study, secondary data analysis was conducted using confirmatory factor
      analysis (CFA) to shorten the PMH instrument. In the second study, the newly
      developed short PMH instrument and other scales were administered to 201
      residents to establish its factor structure, validity and reliability. RESULTS: A
      20-item short PMH instrument fulfilling a higher-order six-factor structure was
      developed following secondary analysis. The mean age of the participants in the
      second study was 41 years and about 53% were women. One item with poor factor
      loading was further removed to generate a 19-item version of the PMH instrument.
      CFA demonstrated a first-order six-factor model of the short PMH instrument. The
      PMH-19 instrument and its subscales fulfilled criterion validity hypotheses.
      Internal consistency and test-retest reliability of the PMH-19 instrument were
      high (Cronbach's alpha coefficient = 0.87; intraclass correlation coefficient =
      0.93, respectively). CONCLUSIONS: The 19-item PMH instrument is multidimensional,
      valid and reliable, and most importantly, with its reduced administration time,
      the short PMH instrument can be used to measure and evaluate PMH in Asian
      communities.

PMID- 24307211
TI  - Testing gender invariance of the hospital anxiety and depression scale using the
      classical approach and Bayesian approach.
AB  - PURPOSE: Measurement invariance is an important attribute for the Hospital
      Anxiety and Depression Scale (HADS). Most of the confirmatory factor analysis
      studies on the HADS adopt the classical maximum likelihood approach. The
      restrictive assumptions of exact-zero cross-loadings and residual correlations in
      the classical approach can lead to inadequate model fit and biased parameter
      estimates. The present study adopted both the classical approach and the
      alternative Bayesian approach to examine the measurement and structural
      invariance of the HADS across gender. METHODS: A Chinese sample of 326 males and
      427 females was used to examine the two-factor model of the HADS across gender.
      Configural and scalar invariance of the HADS were evaluated using the classical
      approach with the robust-weighted least-square estimator and the Bayesian
      approach with zero-mean, small-variance informative priors to cross-loadings and
      residual correlations. RESULTS: Acceptable and excellent model fits were found
      for the two-factor model under the classical and Bayesian approaches,
      respectively. The two-factor model displayed scalar invariance across gender
      using both approaches. In terms of structural invariance, females showed a
      significantly higher mean in the anxiety factor than males under both approaches.
      CONCLUSION: The HADS demonstrated measurement invariance across gender and
      appears to be a well-developed instrument for assessment of anxiety and
      depression. The Bayesian approach is an alternative and flexible tool that could
      be used in future invariance studies.

PMID- 24307212
TI  - Cancer patient-reported outcomes assessment using wireless touch screen tablet
      computers.
AB  - PURPOSE: To assess the feasibility of collecting patient-reported outcomes data
      with wireless touch screen tablet computers in the adult oncology palliative care
      setting. METHODS: Patients were provided with tablet computers during scheduled
      clinic visits and answered online queries about their experience over the past
      week in the health domains of anxiety, depression, fatigue, pain interference,
      physical function, instrumental social support, sleep impairment, diarrhea,
      constipation, nausea, vomiting, anorexia, dyspnea, neuropathy, and spiritual
      values. RESULTS: Content analysis of patient interviews indicates that wireless
      touch screen tablet computers are a feasible approach for collecting patient
      reported outcome measures by palliative care cancer patients presenting in
      clinic. Most patients indicated that the questionnaire was easy to answer.
      However, all but one patient requested some form of assistance, and many reported
      difficulties attributable to a lack of familiarity with the device,
      interpretation of certain questions, and wireless connectivity-related issues.
      CONCLUSIONS: This feasibility study demonstrates that tablet computers have the
      potential to efficiently and reliably collect patient-reported health status
      measures among palliative care cancer patients presenting in clinics. The use of
      these devices may lead to substantial improvements by making patient-reported
      outcomes available for clinical decision-making.

PMID- 24307213
TI  - The replication initiation protein Sld2 regulates helicase assembly.
AB  - Assembly of the Cdc45-Mcm2-7-GINS (CMG) replicative helicase complex must be
      regulated to ensure that DNA unwinding is coupled with DNA synthesis. Sld2 is
      required for the initiation of DNA replication in budding yeast. We identified a
      mutant of Sld2, Sld2-m1,4, that is specifically defective in Mcm2-7 binding. When
      this sld2-m1,4 mutant is expressed, cells exhibit severe inhibition of DNA
      replication. Furthermore, the CMG complex assembles prematurely in G1 in mutant
      cells, but not wild-type cells. These data suggest that Sld2 binding to Mcm2-7 is
      essential to block the inappropriate formation of a CMG helicase complex in G1.
      We also study a mutant of Sld2 that is defective in binding DNA, sld2-DNA, and
      find that sld2-DNA cells exhibit no GINS-Mcm2-7 interaction. These data suggest
      that Sld2 association with DNA is required for CMG assembly in S phase. 

PMID- 24307216
TI  - Heavy metals in agricultural landscapes as hazards to human and ecosystem health:
      a case study on zinc and cadmium in drainage channel sediments.
AB  - BACKGROUND: In agricultural systems, heavy metals pose severe risks to the health
      of soil-plant-animal-human continuum. Drainage channels, as integral components
      of agricultural landscapes, contain sediment material that can be both a source
      and a sink of metals and other toxic/persistent elements due to its highly
      reactive interfaces and strong binding affinity. The drainage channel network in
      a case study area of Vojvodina (Serbia) is not appropriately protected from
      contamination, nor is it maintained regularly (e.g. by desilting), thus
      endangering and potentially decreasing the ecological value of surrounding water
      and agricultural land resources, i.e. exposing food production to potential
      contaminants. In this study (2004-2012), Cd and Zn concentrations were analysed
      in 100 samples from 46 drainage channels sediments spread along the areas of the
      most intensive agricultural land use in Vojvodina. RESULTS: Among the samples
      measured, 5% had Cd and 14% had Zn concentrations above the maximally permitted
      levels, indicating that some drainage channel sections have been exposed to
      different point and non-point source pollutants. The maximum detected
      concentrations of the analysed elements were >50% (Zn) and were as much as 11
      fold (Cd) higher than their remediation values. CONCLUSION: There is a strong
      need for the establishment of qualitative monitoring of channel sediment media in
      agro-ecosystems closely linked with complex pollution sources (intensive
      agriculture, industry, urban zones).

PMID- 24307218
TI  - One-pot synthesis of molecular bottle-brush functionalized single-walled carbon
      nanotubes with superior dispersibility in water.
AB  - Molecular bottle-brush functionalized single-walled carbon nanotubes (SWCNTs)
      with superior dispersibility in water are prepared by a one-pot synthetic
      methodology. Elongating the main-chain and side-chain length of molecular bottle
      brushes can further increase SWCNT dispersibility. They show significant
      enhancement of SWCNT dispersibility up to four times higher than those of linear
      molecular functionalized SWCNTs. 

PMID- 24307217
TI  - Comparison of laparoscopy-assisted and open donor right hepatectomy: a
      prospective case-matched study from china.
AB  - BACKGROUND: Laparoscopy-assisted hepatectomy is a new minimally invasive approach
      for graft harvesting in living donors. Only a few liver transplant centers have
      introduced this surgical procedure. METHODS: A prospective case-matched study was
      conducted on 25 consecutive donors who underwent laparoscopy-assisted donor right
      hepatectomy (LADRH) between July 2011 and March 2013 at our transplant center.
      These donors were matched 1:1 according to age, gender, and body mass index with
      25 donors who underwent open donor right hepatectomy (ODRH). RESULTS: LADRH was
      successfully performed in all 25 of the donors. Donor complications, estimated
      blood loss, and operative time were similar between the groups. Hospital stay and
      periods of analgesic use were significantly shorter in the LADRH group [7.0 +/-
      1.4 (LADRH) vs. 8.7 +/- 2.4 (ODRH), p = 0.003, and 2.4 +/- 1.0 (LADRH) vs. 3.2 +/
      1.0 (ODRH), p = 0.011, respectively). The total in-hospital cost is higher with
      LADRH, primarily due to the additional material costs for LADRH. Finally, there
      were no differences in graft size, graft survival, or recipient complications
      between the two groups. CONCLUSION: The results of this study show that LADRH is
      a feasible and safe procedure compared with ODRH. Although higher material costs
      for laparoscopic assisted procedures are inevitable, LADRH may have an advantage
      over ODRH by causing less pain and facilitating earlier recovery. Efforts can be
      made to improve the technical success of LADRH for some overweight donors.

PMID- 24307219
TI  - Micropatterned polymeric nanosheets for local delivery of an engineered
      epithelial monolayer.
AB  - Like a carpet for cells, micropatterned polymeric nanosheets are developed toward
      local cell delivery. The nanosheets direct morphogenesis of retinal pigment
      epithelial (RPE) cells and allow for the injection of an engineered RPE monolayer
      through syringe needles without the loss of cell viability. Such an ultrathin
      carrier has the promise of a minimally invasive delivery of cells into narrow
      tissue spaces. 

PMID- 24307220
TI  - The real-world dose-relativity of sevelamer hydrochloride and lanthanum carbonate
      monotherapy in patients with end-stage renal disease.
AB  - INTRODUCTION: Sevelamer hydrochloride (SH) and lanthanum carbonate (LC) are
      calcium-free phosphate binders used for the management of hyperphosphatemia in
      patients with end-stage renal disease (ESRD). The objective of this analysis was
      to evaluate the real-world dose-relativity between SH and LC monotherapy in US
      patients with ESRD. METHODS: This was a post hoc analysis of a 16-week, real
      world study (Vemuri et al. in BMC Nephrol 12:49, 2011) of the efficacy of
      conversion to LC monotherapy from other phosphate binders. The SH:LC dose
      relativity ratio, based on the mean daily dose, was calculated in the subset of
      patients from the Vemuri study who converted from SH to LC monotherapy and had
      available SH and LC dose data. RESULTS: A total of 950 patients converted from SH
      to LC monotherapy and had recorded dose data. The post hoc analysis population
      comprised 691 patients with available dose data for both SH at baseline and LC at
      week 16. The mean (SD) serum phosphate level at baseline was 5.91 (1.66) mg/dL.
      After conversion to LC monotherapy for 16 weeks, the mean (SD) serum phosphate
      level was 5.93 (1.85) mg/dL. The mean (SD) daily baseline SH dose was 7,703
      (3,642) mg and the mean (SD) daily LC dose at week 16 was 2,800 (939) mg (9.6
      versus 2.8 tablets, respectively; P < 0.0001), resulting in a SH:LC dose
      relativity ratio of 2.8. The median individual patient SH:LC dose-relativity
      ratio was 2.6 (95% CI 2.6-2.8). Across baseline SH dose subgroups (2,400-4,800,
      >4,800-7,200, >7,200-9,600, and >9,600 mg/day), the mean daily SH dose was 4,051,
      7,047, 9,253, and 13,150 mg, respectively. In comparison, the mean daily LC dose
      was 2,445-3,156 mg. Thus, patients requiring baseline SH doses >7,200 mg/day (41%
      of the analysis population) had higher SH:LC dose-relativity ratios of 3.1-4.2
      (median individual patient ratios 3.1-4.0). CONCLUSION: In this post hoc analysis
      of real-world dose-relativity, the overall SH:LC dose-relativity ratio was 2.8
      (median individual patient ratio 2.6 (95% CI 2.6-2.8). These findings are
      consistent with the World Health Organization-defined daily dose and previous
      studies of the relative phosphate binding capacity of the two drugs. Patients
      requiring SH doses >7,200 mg/day had higher SH:LC dose-relativities of 3.1-4.2
      (median individual patient ratios 3.1-4.0). These findings have implications for
      the tablet burden and cost-effectiveness of SH and LC in the treatment of
      hyperphosphatemia.

PMID- 24307221
TI  - Comparative short-term effect of once-daily molsidomine on chronic angina in
      general practitioners' versus cardiologists' coronary patient populations.
AB  - INTRODUCTION: The direct nitric oxide donor molsidomine is commonly used to
      relieve symptoms in chronic angina thanks to its vasodilatory properties that
      induce both a reduction in myocardial oxygen demand and an increase in coronary
      blood flow. The objective of this study was to compare the short-term effect of
      molsidomine 16 mg once daily (Coruno((r)), Therabel Pharmaceuticals Ltd, Dublin,
      Ireland) in patients with stable angina previously on molsidomine 8 mg twice
      daily, in care of general practitioners (GPs) versus cardiologists. METHODS: A
      total of 53 and 80 patients treated by GPs and cardiologists, respectively, took
      part in this multicenter, open-label clinical trial. Frequency of anginal
      attacks, short-acting nitroderivative tablets consumption, and subjective
      clinical status were evaluated, as was tolerability to molsidomine through the
      reporting of adverse events (AEs), the recording of vital parameters-resting
      blood pressure, heart rate, and electrocardiogram-and routine blood analyses.
      RESULTS: Although demographic and clinical characteristics were significantly
      different in GPs' compared with cardiologists' patients, the effect of either the
      8 mg or the 16 mg molsidomine formulation on anginal crises and nitroderivatives
      consumption was similar in both patient cohorts, with a trend for the 16 mg
      formulation to be more efficient on symptoms in elderly patients. Subjective
      assessment of the beneficial effect of molsidomine 16 versus 8 mg was comparable
      in GPs' and cardiologists' patients independently of age, "no change" being the
      most often reported item. Self-evaluation of functional capacity in elderly
      showed on the whole no difference between the two patient cohorts, only magnitude
      of pace and total score on molsidomine 16 mg being higher in cardiologists'
      compared with GPs' patients, and total score in cardiologists' patients higher on
      molsidomine 16 mg compared with 8 mg. Incidences of AEs and drug-related AEs, as
      well as proportions of patients reporting such AEs, were similar between GPs' and
      cardiologists' patient cohorts as between molsidomine 8 and 16 mg formulations.
      Molsidomine 16 mg once daily had no clinically significant effect on blood
      pressure, heart rate, electrocardiogram or blood parameters, and compliance with
      treatment was excellent in whatever patient cohort. CONCLUSION: Despite
      significant demographic and clinical differences between patients in care of GPs
      and cardiologists, molsidomine was equally efficient in these two patient
      cohorts, with a trend towards less anginal attacks in the elderly when treated
      with the 16 mg compared with the 8 mg formulation. Compliance and tolerability to
      the drug were excellent in both patient cohorts.

PMID- 24307222
TI  - An efficient multistep ligand-based virtual screening approach for GPR40
      agonists.
AB  - G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) is a
      member of the GPCR superfamily, and GPR40 agonists have therapeutic potential for
      type 2 diabetes. With the crystal structure of GPR40 currently unavailable,
      various ligand-based virtual screening approaches can be applied to identify
      novel agonists of GPR40. It is known that each ligand-based method has its own
      advantages and limitations. To improve the efficiency of individual ligand-based
      methods, an efficient multistep ligand-based virtual screening approach is
      presented in this study, including the pharmacophore-based screening,
      physicochemical property filtering, protein-ligand interaction fingerprint
      similarity analysis, and 2D-fingerprint structural similarity search. A focused
      decoy library was generated and used to evaluate the efficiency of this virtual
      screening protocol. This multistep workflow not only significantly improved the
      hit rate compared with each individual ligand-based method, but also identified
      diverse known actives from decoys. This protocol may serve as an efficient
      virtual screening tool for the targets without crystal structures available to
      discover novel active compounds. 

PMID- 24307223
TI  - Purification and characterization of 8 of the pathogenesis-related proteins in
      tobacco leaves reacting hypersensitively to tobacco mosaic virus.
AB  - Leaves of tobacco plants (Nicotiana tabacum cv. Samsun NN) which are reacting
      hypersensitively to infection with tobacco mosaic virus contain 10 major
      pathogenesis-related (PR) proteins which are absent, or present in small amounts
      in uninfected leaves. We describe here a preparative procedure of purification of
      the tobacco PR-proteins which involves a combination of conventional and high
      performance liquid chromatography. The separation and isolation of the proteins
      were based on differences in net charge at different pH values, in isoelectric
      point and in apparent molecular weight. This procedure led to the purification to
      homogeneity of 8 PR-proteins, as shown by polyacrylamide slab gel electrophoresis
      (PAGE) of the purified proteins under denaturing and non-denaturing conditions.
      These were the 3 well-known proteins PR-1a,-1b and-1c, and 5 other major PR
      proteins, called PR-2,-N,-O,-P and-Q, according to the nomenclature of Van Loon
      (39). None of the purified PR-proteins gave a positive Schiff reaction for
      carbohydrate content. Molecular weight determinations from gel permeation
      chromatography and from sodium dodecyl sulphate (SDS)-PAGE indicated that all 8
      PR-proteins were monomers and that three groups could be distinguished among
      them. The first group is the PR-1 group containing PR-1a,-1b and-1c (12000 MW),
      the second consists of PR-P and PR-Q (14000 MW) and the third of PR-2, PR-N and
      PR-O (25000 MW). In the PR-1 group, PR-1a can be distinguished clearly from the
      two other members on denaturing slab gels containing both SDS and urea. 

PMID- 24307224
TI  - Nicotiana chloroplast genome: X. Correlation between the DNA sequences and the
      isoelectric focusing patterns of the LS of Rubisco.
AB  - Comparison of the DNA sequences of the rbcL gene from three Nicotiana species
      reveals a high degree of homology among the 1431 bp in the coding region. Only
      eight base pair differences are observed between N. otophora and N. tabacum, and
      between N. otophora and N. acuminata. Four base pair differences are observed
      between N. acuminata and N. tabacum. Most changes are in the third position of
      the codon resulting in only two amino acid alterations when N. otophora and N.
      acuminata are compared with N. tabacum. Evidence is presented demonstrating that
      the amino acid compositions of the LS derived from the DNA sequence are related
      to the IEF cluster pattern. A single charged residue is responsible for the
      difference in cluster pattern. 

PMID- 24307225
TI  - Accurate transcription and processing of 19 Euglena chloroplast tRNAs in a
      Euglena soluble extract.
AB  - The transcription and accurate processing of 19 different Euglena gracilis
      chloroplast tRNAs in a homologous chloroplast soluble extract is described. The
      chloroplast DNA dependent-RNA polymerase present in the extract selectively
      transcribes the tRNA genes (Greenberg et al., 1984, J. Biol. Chem., 259: 14880
      14887). Two dimensional polyacrylamide gel electrophoresis and RNA fingerprint
      analysis were used to show that the tRNAs are correctly processed at the 5'- and
      3'-ends. The Euglena chloroplast soluble extract contains a 5'-processing or
      'RNase P-like' activity and RNases responsible for processing tRNA termini.
      However, it was not determined if the 3'-CCA was added. Therefore, the soluble
      extract contains activities that are quite similar to an extract of spinach
      chloroplasts (Greenberg et al. (1984), Plant Mol. Biol., 3: 97-109). After
      transcription of total chloroplast DNA in the Euglena soluble extract, thirty
      three tRNA sized products were resolved by two dimensional polyacrylamide gel
      electrophoresis. Nineteen tRNAs could be identified in this mixture. 

PMID- 24307226
TI  - Independent integration and seed-transmission of the TR-DNA of the octopine Ti
      plasmid pTi Ach5 in Nicotiana plumbaginifolia.
AB  - After co-cultivation of diploid Nicotiana plumbaginifolia protoplasts with an
      octopine-type Agrobacterium tumefaciens strain (LBA 4013) putative transformants
      were selected for hormone-independent growth, and were tested for T-DNA markers.
      The number of transformants expressing only TL-DNA markers, i.e. phytohormone
      autotrophy and octopine synthase, was an order of magnitude higher than that of
      the cell lines which were simultaneously positive for both TL- and TR-DNA markers
      (the latter being mannopine and agropine). In one transformant, line no. 101,
      only the TR-DNA markers were found. Not each of the TL-, or TR-DNA markers were
      expressed in each transformant resulting in a variety of phenotypes. It included
      the unorganized or the shoot-teratoma type of growth combined with the presence
      or absence of opines; e.g. agropine was absent from some of the transformants
      containing its precursor, mannopine. 5-Azacytidine did not induce agropine
      synthesis in these lines. Southern blot analysis showed that the TR-DNA region
      coding for agropine synthesis was rearranged or absent in one of these lines.
      Similar variation in the expression of agropine and mannopine production was
      observed in transformants obtained with the leucinopine-type strain A281.From
      line 101 plants could be easily regenerated with the ability to synthesize
      agropine and mannopine. The segregation in the self-progeny fitted to a 3:1
      ratio, indicating that the TR-DNA was carried by a single chromosome. The
      Southern blot analysis showed that only opine-positive plants contained TR-DNA.
      It also confirmed the absence of the TL-DNA, demonstrating the independent
      integration of the TR-region of the octopine-type Ti plasmid pTi Ach5. 

PMID- 24307227
TI  - Comparison between the organization of nuclear ribosomal DNA unit of Euglena
      gracilis Z and var. Bacillaris.
AB  - We have characterized the nuclear rDNA unit of Euglena gracilis var. bacillaris
      and compared it to that of the Z strain. We have localized restriction sites for
      Eco R1, Sal 1, Sma 1, Hind III, Bam H1 and Bgl II on this unit as well as the
      coding region for 20 S and 25 S rRNAs. For both strains, results suggest an
      homogeneity of the 11.6 kbp rDNA units. Comparison between strains shows
      differences characterized by two additional Sal 1 sites in bacillaris and the
      likely methylation of one Sma 1 site in Z. Both differences are localized in a
      non-coding region of the rDNA unit. Analyses of 18 Euglena strains from various
      origins confirm these differences and allow easy recognition of bacillaris and Z
      type strains. 

PMID- 24307228
TI  - A physical map of the sorghum chloroplast genome.
AB  - The chloroplast genome of the IS1112C cytoplasm of sorghum was mapped by the
      construction of a Bam-HI library in pUC8, and hybridization with BamHI, SalI, and
      PstI digests of chloroplast DNA (ctDNA) of sorghum and maize. The molecules are
      extensively colinear, with only one of 13 SalI fragments differing slightly from
      maize. Seven of 70 restriction sites differed in the two species. A total
      molecular size of ca. 138 kb was estimated for sorghum. The inverted repeat was
      not conserved between sorghum and maize, as revealed by a slightly larger BamHI
      16S rDNA fragment in sorghum. Homology of a sequence adjacent to the gammabcl
      gene and one end of the inverted repeat was detected. These homologies were also
      observed in maize, and suggest that the ctDNA genomes of sorghum and maize share
      small reiterations of sequences of the inverted repeat. 

PMID- 24307229
TI  - Localization of the genes coding for the 51 kDa PSII chlorophyll apoprotein,
      apocytochrome b6, the 65-70 kDa PSI chlorophyll apoproteins and the 44 kDa PSII
      chlorophyll apoprotein in pea chloroplast DNA.
AB  - DNA probes isolated from previously mapped spinach genes were used to locate 5
      genes on pea ctDNA by heterologous hybridization. The genes mapped include psbC,
      psaA, psaB, psbB, and petB. PsbB and petB mapped to a 6.7 kbp XbaI DNA fragment
      adjacent to the petD gene. Northern probes from within the DNA which codes for
      psbB and petD hybridized to 6 RNAs ranging from 1.2 to 5.6 kbp. The psaA and psaB
      genes, which code for 65-70 kDa proteins of Photosystem I, were mapped to a 7.5
      kbp. XbaI DNA fragment. A 5.8 kbp RNA is transcribed from the region which
      contains the psaA and psaB genes suggesting that these genes are co-transcribed.
      Finally the psbC gene which codes for a 44 kDa chlorophyll-protein of Photosystem
      II was mapped to a 12.3 kbp PstI DNA fragment. The pea psbC open reading frame
      overlaps the psbD coding sequence and this gene pair is within 3 kbp of the psaA
      psaB genes. Overall, the organization of the 3 gene clusters analyzed in peas is
      similar to that reported for spinach. 

PMID- 24307230
TI  - ARX/Arx is expressed in germ cells during spermatogenesis in both marsupial and
      mouse.
AB  - The X-linked aristaless gene, ARX, is essential for the development of the
      gonads, forebrain, olfactory bulb, pancreas, and skeletal muscle in mice and
      humans. Mutations cause neurological diseases, often accompanied by ambiguous
      genitalia. There are a disproportionately high number of testis and brain genes
      on the human and mouse X chromosomes. It is still unknown whether the X
      chromosome accrued these genes during its evolution or whether genes that find
      themselves on the X chromosome evolve such roles. ARX was originally autosomal in
      mammals and remains so in marsupials, whereas in eutherian mammals it
      translocated to the X chromosome. In this study, we examined autosomal ARX in
      tammars and compared it with the X-linked Arx in mice. We detected ARX mRNA in
      the neural cells of the forebrain, midbrain and hindbrain, and olfactory bulbs in
      developing tammars, consistent with the expression in mice. ARX was detected by
      RT-PCR and mRNA in situ hybridization in the developing tammar wallaby gonads of
      both sexes, suggestive of a role in sexual development as in mice. We also
      detected ARX/Arx mRNA in the adult testis in both tammars and mice, suggesting a
      potential novel role for ARX/Arx in spermiogenesis. ARX transcripts were
      predominantly observed in round spermatids. Arx mRNA localization distributions
      in the mouse adult testis suggest that it escaped meiotic sex chromosome
      inactivation during spermatogenesis. Our findings suggest that ARX in the therian
      mammal ancestor already played a role in male reproduction before it was
      recruited to the X chromosome in eutherians. 

PMID- 24307231
TI  - Can adults with autism spectrum disorders infer what happened to someone from
      their emotional response?
AB  - Can adults with autism spectrum disorders (ASD) infer what happened to someone
      from their emotional response? Millikan has argued that in everyday life, others'
      emotions are most commonly used to work out the antecedents of behavior, an
      ability termed retrodictive mindreading. As those with ASD show difficulties
      interpreting others' emotions, we predicted that these individuals would have
      difficulty with retrodictive mindreading. Sixteen adults with high-functioning
      autism or Asperger's syndrome and 19 typically developing adults viewed 21 video
      clips of people reacting to one of three gifts (chocolate, monopoly money, or a
      homemade novelty) and then inferred what gift the recipient received and the
      emotion expressed by that person. Participants' eye movements were recorded while
      they viewed the videos. Results showed that participants with ASD were only less
      accurate when inferring who received a chocolate or homemade gift. This
      difficulty was not due to lack of understanding what emotions were appropriate in
      response to each gift, as both groups gave consistent gift and emotion inferences
      significantly above chance (genuine positive for chocolate and feigned positive
      for homemade). Those with ASD did not look significantly less to the eyes of
      faces in the videos, and looking to the eyes did not correlate with accuracy on
      the task. These results suggest that those with ASD are less accurate when
      retrodicting events involving recognition of genuine and feigned positive
      emotions, and challenge claims that lack of attention to the eyes causes emotion
      recognition difficulties in ASD.

PMID- 24307232
TI  - ?

PMID- 24307233
TI  - [Quality of Mesorectal Excision ("Plane of Surgery") - Which Quality Targets are
      Adequate?].
AB  - Today, the examination of rectal cancer specimens includes the obligate
      macroscopic assessment of the quality of mesorectal excision by the pathologist
      reporting the plane of surgery. The frequency of operations in the muscularis
      propria plane of surgery (earlier described as incomplete mesorectal excision) is
      essential. The quality of mesorectal excision is important for the prognosis,
      especially as local recurrences are observed more frequently after operations in
      the muscularis propria plane of surgery. For the definition of quality targets,
      data of 13 studies published between 2006 and 2012, each with more than 100
      patients and adequate specialisation and experience of the surgeons (5413
      patients), data of the prospective multicentric observation study "Quality
      Assurance - Rectal Cancer" (at the Institute for Quality Assurance in Operative
      Medicine at the Otto-von-Guericke University at Magdeburg) from 2005 to 2010
      (8044 patients) and data of the Department of Surgery, University Hospital
      Erlangen, from 1998 to 2011 (991 patients) were analysed. The total incidence of
      operations in the muscularis propria plane of surgery was 5.0 % (721/14 448).
      Even with adequate specialisation and experience of the surgeon, the frequency of
      operations in the muscularis propria plane of surgery is higher in
      abdominoperineal excisions than in sphincter-preserving surgery (8.4 vs. 2.8 %, p
      < 0.001). Thus, the quality target for the frequency of operations in the
      muscularis propria plane should be defined as < 5 % for sphincter-preserving
      procedures and as < 10 % for abdominoperineal excisions. 

PMID- 24307234
TI  - Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria
      dependent apoptosis.
AB  - Very limited information regarding the influence of chronic methamphetamine
      exposure on cardiac apoptosis is available. In this study, we evaluate whether
      chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and
      mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats
      at 3-4 months of age were randomly divided into a vehicle-treated group
      [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated
      group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of
      exposure, abnormal myocardial architecture, more minor cardiac fibrosis and
      cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the
      MA group than in the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas
      receptor, Fas-associated death domain, activated caspase-8, and activated caspase
      3 (Fas-dependent apoptosis) extracted from excised hearts were significantly
      increased in the MA group, compared to the PBS group. Protein levels of cardiac
      Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3
      (mitochondria-dependent apoptosis) were significantly increased in the MA group,
      compared with the PBS group. The results from this study reveal that chronic
      methamphetamine exposure will activate cardiac Fas-dependent and mitochondria
      dependent apoptotic pathways, which may indicate a possible mechanism for
      developing cardiac abnormalities in humans with chronic methamphetamine abuse.

PMID- 24307235
TI  - Physicians' experiences and perspectives regarding the use of continuous sedation
      until death for cancer patients in the context of psychological and existential
      suffering at the end of life.
AB  - OBJECTIVE: The use of continuous sedation until death for terminally ill cancer
      patients with unbearable and untreatable psychological and existential suffering
      remains controversial, and little in-depth insight exists into the circumstances
      in which physicians resort to it. METHODS: Our study was conducted in Belgium,
      the Netherlands, and the UK in hospitals, PCUs/hospices, and at home. We held
      interviews with 35 physicians most involved in the care of cancer patients who
      had psychological and existential suffering and had been continuously sedated
      until death. RESULTS: In the studied countries, three groups of patients were
      distinguished regarding the origin of their psychological and existential
      suffering. The first group had preexisting psychological problems before they
      became ill, the second developed psychological and existential suffering during
      their disease trajectory, and the third presented psychological symptoms that
      were characteristic of their disease. Before they resorted to the use of
      sedation, physicians reported that they had considered an array of
      pharmacological and psychological interventions that were ineffective or
      inappropriate to relieve this suffering. Necessary conditions for using sedation
      in this context were for most physicians the presence of refractory symptoms, a
      short life expectancy, and an explicit patient request for sedation. CONCLUSIONS:
      Physicians in our study used continuous sedation until death in the context of
      psychological and existential suffering after considering several pharmacological
      and psychological interventions. Further research and debate are needed on how
      and by whom this suffering at the end of life should be best treated, taking into
      account patients' individual preferences.

PMID- 24307236
TI  - Macrophage depletion reduces cell proliferation and extracellular matrix
      accumulation but increases the ultimate tensile strength of injured Achilles
      tendons.
AB  - Macrophages are present in large numbers and display specific and distinct
      phenotypes during the various phases of tissue repair. However, their role
      following tendon injury and during repair has never been investigated. We
      injected C57BL/6 mice daily for 4 days with liposome-encapsulated clodronate to
      deplete circulating monocytes/macrophages. Placebo mice were injected with PBS.
      The left Achilles tendons of the mice were transversely sectioned and sutured
      using the 8-strand technique. Macrophage accumulation and cell proliferation were
      significantly lower in the tendons of clodronate-treated mice than in those of
      PBS-treated mice on days 3 and 7 post-injury. TGF-beta1 staining was
      significantly more intense in the tendons of PBS-treated mice on day 7 post
      injury. Edema and the dry mass of the Achilles tendons were also higher in the
      PBS-treated mice on days 7 and 14 post-injury. No differences in absolute
      strength and stiffness were observed, but Young's modulus and maximal stress were
      significantly greater for tendons from the clodronate-treated mice than those
      from PBS-treated mice after 14 days of tendon repair. Overall, our findings
      showed that macrophages promote cell proliferation and extracellular matrix
      accumulation but their presence leads to inferior ultimate tensile strength of
      the Achilles tendons.

PMID- 24307237
TI  - Multicomponent synthesis of unsymmetrical unsaturated N-heterocyclic carbene
      precursors and their related transition-metal complexes.
AB  - A low-cost, modular, and easily scalable multicomponent procedure affording
      access in good yields and excellent selectivity (up to 93%) to a wide range of
      (a)chiral unsymmetrical 1-aryl-3-cycloalkyl-imidazolium salts is disclosed.
      Electronic and steric properties of the corresponding unsymmetrical unsaturated N
      heterocyclic carbene (U2-NHC) ligands were evaluated and evidenced strong
      electron donor ability, high steric discrimination, and modular steric demand.

PMID- 24307238
TI  - Immunological characterization of a modified vaccinia virus Ankara vector
      expressing the human papillomavirus 16 E1 protein.
AB  - Women showing normal cytology but diagnosed with a persistent high-risk human
      papillomavirus (HR-HPV) infection have a higher risk of developing high-grade
      cervical intraepithelial neoplasia and cervical cancer than noninfected women. As
      no therapeutic management other than surveillance is offered to these women,
      there is a major challenge to develop novel targeted therapies dedicated to the
      treatment of these patients. As such, E1 and E2 antigens, expressed early in the
      HPV life cycle, represent very interesting candidates. Both proteins are
      necessary for maintaining coordinated viral replication and gene synthesis during
      the differentiation process of the epithelium and are essential for the virus to
      complete its normal and propagative replication cycle. In the present study, we
      evaluated a new active targeted immunotherapeutic, a modified vaccinia virus
      Ankara (MVA) vector containing the E1 sequence of HPV16, aimed at inducing
      cellular immune responses with the potential to help and clear persistent HPV16
      related infection. We carried out an extensive comparative time course analysis
      of the cellular immune responses induced by different schedules of immunization
      in C57BL/6 mice. We showed that multiple injections of MVA-E1 allowed sustained
      HPV16 E1-specific cellular immune responses in vaccinated mice and had no impact
      on the exhaustion phenotype of the generated HPV16 E1-specific CD8+ T cells, but
      they led to the differentiation of multifunctional effector T cells with high
      cytotoxic capacity. This study provides proof of concept that an MVA expressing
      HPV16 E1 can induce robust and long-lasting E1-specific responses and warrants
      further development of this candidate.

PMID- 24307239
TI  - Intramuscular delivery of adenovirus serotype 5 vector expressing humanized
      protective antigen induces rapid protection against anthrax that may bypass
      intranasally originated preexisting adenovirus immunity.
AB  - Developing an effective anthrax vaccine that can induce a rapid and sustained
      immune response is a priority for the prevention of bioterrorism-associated
      anthrax infection. Here, we developed a recombinant replication-deficient
      adenovirus serotype 5-based vaccine expressing the humanized protective antigen
      (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and
      robust humoral and cellular immune responses in Fisher 344 rats. Animals
      intramuscularly inoculated with a single dose of 108 infectious units of Ad5
      PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose
      (LD50) of anthrax lethal toxin 7 days after vaccination. Although preexisting
      intranasally induced immunity to Ad5 slightly weakened the humoral and cellular
      immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was
      achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy
      conferred by intramuscular vaccination in the presence of preexisting
      intranasally induced immunity was significantly better than that of intranasal
      delivery of Ad5-PAopt and intramuscular injection with recombinant PA and
      aluminum adjuvant without preexisting immunity. As natural Ad5 infection often
      occurs via the mucosal route, the work here largely illuminates that
      intramuscular inoculation with Ad5-PAopt can overcome the negative effects of
      immunity induced by prior adenovirus infection and represents an efficient
      approach for protecting against emerging anthrax.

PMID- 24307240
TI  - Antibody responses to Bordetella pertussis Fim2 or Fim3 following immunization
      with a whole-cell, two-component, or five-component acellular pertussis vaccine
      and following pertussis disease in children in Sweden in 1997 and 2007.
AB  - Bordetella pertussis fimbriae (Fim2 and Fim3) are components of a five-component
      acellular pertussis vaccine (diphtheria-tetanus-acellular pertussis vaccine
      [DTaP5]), and antibody responses to fimbriae have been associated with
      protection. We analyzed the IgG responses to individual Fim2 and Fim3 in sera
      remaining from a Swedish placebo-controlled efficacy trial that compared a whole
      cell vaccine (diphtheria-tetanus-whole-cell pertussis vaccine [DTwP]), a two
      component acellular pertussis vaccine (DTaP2), and DTaP5. One month following
      three doses of the Fim-containing vaccines (DTwP or DTaP5), anti-Fim2 geometric
      mean IgG concentrations were higher than those for anti-Fim3, with a greater anti
      Fim2/anti-Fim3 IgG ratio elicited by DTaP5. We also determined the responses in
      vaccinated children following an episode of pertussis. Those who received DTaP5
      showed a large rise in anti-Fim2 IgG, reflecting the predominant Fim2 serotype at
      the time. In contrast, those who received DTwP showed an equal rise in anti-Fim2
      and anti-Fim3 IgG concentrations, indicating that DTwP may provide a more
      efficient priming effect for a Fim3 response following contact with B. pertussis.
      Anti-Fim2 and anti-Fim3 IgG concentrations were also determined in samples from
      two seroprevalence studies conducted in Sweden in 1997, when no pertussis vaccine
      was used and Fim2 isolates predominated, and in 2007, when either DTaP2 or DTaP3
      without fimbriae was used and Fim3 isolates predominated. Very similar
      distributions of anti-Fim2 and anti-Fim3 IgG concentrations were obtained in 1997
      and 2007, except that anti-Fim3 concentrations in 1997 were lower. This
      observation, together with the numbers of individuals with both anti-Fim2 and
      anti-Fim3 IgG concentrations, strongly suggests that B. pertussis expresses both
      Fim2 and Fim3 during infection. 

PMID- 24307241
TI  - Endovenous saphenous vein ablation in patients with acute isolated superficial
      vein thrombosis.
AB  - OBJECTIVE: The possible benefits of endovenous saphenous ablation (EVSA) as
      initial treatment in patients presenting with isolated superficial-vein
      thrombosis (SVT) and saphenous vein reflux include: (1) definitive treatment of
      the underlying pathology and (2) elimination of the saphenous vein as a path for
      pulmonary emboli, which (3) may eliminate the need for anticoagulation. METHODS:
      In a ten-year review of 115 limbs presenting with acute isolated SVT, 72 limbs
      (71 patients) with saphenous reflux were given a choice of two treatments
      following an explanation of the risks and benefits of each. Group I limbs (n =
      41) were treated with office EVSA using radiofrequency or laser with or without
      thrombophlebectomy if performed within 45 days of diagnosis. Post-treatment
      anticoagulants were not given. Group II limbs (n = 31) were treated with
      compression hose and repeat Duplex within one week, with added anticoagulants if
      SVT extended into the thigh. RESULTS: In group I, mean interval from diagnosis to
      treatment was 13.7 days. One calf deep vein thrombosis was noted. In group II no
      complications were noted. In late follow-up of group II patients, 12/29 underwent
      EVSA more than 45 days after initial presentation. CONCLUSIONS: The safety and
      efficacy of EVSA and thrombophlebectomy appear indistinguishable from
      conservative measures and may be offered as initial treatment to patients
      presenting with SVT and saphenous reflux.

PMID- 24307242
TI  - Study on different bandages and application techniques for achieving stiffer
      compression.
AB  - OBJECTIVES: The objective of this study was to investigate the relationship
      between interface pressure and stiffness of compression achieved by various
      combinations of bandages and application techniques. METHOD: There were eight
      healthy volunteers. One roll (4.5 m) of four types of bandages with different
      extensibilities (0, 90, 108 and 218%) was applied to the leg in single-layer
      bandage fashion with eight random tensions. Then, the leg was wrapped with one to
      eight rolls in multi-layer bandage fashion. RESULTS: Each combination of bandage
      and application technique displayed an indigenous linear interface pressure
      static stiffness index relationship. With single-layer bandage, lower
      extensibility was associated with higher static stiffness index at a given
      interface pressure. With multi-layer bandage, the static stiffness index at a
      given interface pressure was independent of the bandage type. CONCLUSION: The
      stiffness at a given interface pressure was affected by the extensibility with
      single-layer bandage but not with multi-layer bandage.

PMID- 24307243
TI  - IL-4-induced gene 1 maintains high Tob1 expression that contributes to TCR
      unresponsiveness in human T helper 17 cells.
AB  - Human Th17 cells have a limited proliferative capacity compared to other T-cell
      subsets. We have shown that human Th17 cells display impaired IL-2 production due
      to IL-4-induced gene 1 (IL4I1) upregulation. Here, we show that in human Th17
      cells, IL4I1 also maintains high levels of Tob1, a member of the Tob/BTG (B-cell
      traslocation gene) antiproliferative protein family, which prevents cell-cycle
      progression mediated by TCR stimulation. Indeed, Th17 cells exhibited higher
      levels of Tob1 than Th1 cells in both resting and TCR-activated conditions.
      Accordingly, the expression of positive regulators of the cell cycle (cyclin A,
      B, C, and E and Cdk2), as well as of Skp2, which promotes Tob1 degradation, was
      lower in Th17 cells than in Th1 cells. Tob1 expression in human Th17 cells
      correlated with both RAR (retinoic acid receptor)-related orphan receptor C
      (RORC) and IL4I1 levels. However, RORC was not directly involved in the
      regulation of Tob1 expression, whereas IL4I1 silencing in Th17 cells induced a
      substantial decrease of Tob1 expression. These data suggest that IL4I1
      upregulation in human Th17 cells limits their TCR-mediated expansion not only by
      blocking the molecular pathway involved in the activation of the IL-2 promoter,
      but also by maintaining high levels of Tob1, which impairs entry into the cell
      cycle. 

PMID- 24307244
TI  - Controllable co-segregation synthesis of wafer-scale hexagonal boron nitride thin
      films.
AB  - A facile and scalable co-segregation method is used to grow hexagonal boron
      nitride (h-BN) thin films from B- and N-containing metals. By annealing the
      sandwiched metal substrates in vacuum, sub-monolayer h-BN flakes, monolayer h-BN
      films, and multilayer h-BN thin films of varying thickness are successfully
      prepared. This approach follows an underneath-growth mode and exhibits good
      thickness- and location-control. 

PMID- 24307245
TI  - Shoulder strength profiles in children with and without brachial PLEXUS PALSY.
AB  - INTRODUCTION: We characterized bilateral shoulder strength and the balance of
      antagonist/agonist muscle pairs in children with brachial plexus palsy (BPP) and
      with typical development (TD). METHODS: In 15 children with unilateral BPP and 11
      with TD, bilateral maximal isometric shoulder strength in flexion/extension,
      internal/external rotation, and abduction/adduction was recorded using a hand
      held dynamometer. Correlation between strength and active range of motion were
      evaluated using the Mallet score. RESULTS: Children with BPP had strength
      asymmetry in all muscles, whereas children with TD had significant strength
      asymmetry for flexors and abductors. In children with BPP, extensors and external
      rotators were the weakest muscles, leading to sagittal and transverse plane
      muscle imbalances. Higher strength values were related to better active range of
      motion. CONCLUSIONS: This study highlights the importance of documenting shoulder
      strength profiles in children with BPP which may help predict deformity
      development.

PMID- 24307246
TI  - Quantification of Fusarium oxysporum in fumigated soils by a newly developed real
      time PCR assay to assess the efficacy of fumigants for Fusarium wilt disease in
      strawberry plants.
AB  - BACKGROUND: Two soil fumigants, chloropicrin (CP) and dimethyl disulfide (DMDS),
      were used to control Fusarium wilt disease (FWD) which caused large economic
      losses in strawberries. The fumigants were evaluated alone and in combination in
      a laboratory study and in strawberry greenhouses. RESULTS: Laboratory tests found
      that combinations of CP and DMDS indicated a positive synergistic activity on
      Fusarium oxysporum. A newly developed quantitative assay for F. oxysporum
      involving real-time PCR was used successfully to evaluate F. oxysporum control by
      the fumigants; it provided similar results to the selective medium but was less
      time-consuming and less labor intensive. Greenhouse trials revealed that the
      combination of CP and DMDS successfully suppressed the incidence of FWD and
      sharply reduced the population density of F. oxysporum, which significantly
      increased fruit branch number and maintained a good strawberry yield, higher than
      methyl bromide (MB) treatment. All of the treatments provided significantly
      better results than the non-treated control. CONCLUSION: This study confirms that
      the newly developed real-time PCR quantitative assay for F. oxysporum was
      suitable for the control efficacy evaluation of soil fumigants and that the novel
      fumigant combination of CP and DMDS offers a promising effective alternative to
      MB for the control of F. oxysporum in strawberry greenhouses.

PMID- 24307247
TI  - A microvascular system for chemical reactions using surface waste heat.
AB  - Coffee-powered chemistry: Low-grade waste heat on surfaces can be used to drive
      chemical reactions, including the regeneration of a CO2 capture solution. Flowing
      two-phase heat transfer has been implemented within microvascular systems. This
      stripping system can be adapted to pre-fabricated surfaces, as demonstrated by a
      coffee mug containing a 1.2 m long microchannel. MEA=monoethanolamine. 

PMID- 24307248
TI  - The effect of iconicity of visual displays on statistical reasoning: evidence in
      favor of the null hypothesis.
AB  - Knowing which properties of visual displays facilitate statistical reasoning
      bears practical and theoretical implications. Therefore, we studied the effect of
      one property of visual diplays - iconicity (i.e., the resemblance of a visual
      sign to its referent) - on Bayesian reasoning. Two main accounts of statistical
      reasoning predict different effect of iconicity on Bayesian reasoning. The
      ecological-rationality account predicts a positive iconicity effect, because more
      highly iconic signs resemble more individuated objects, which tap better into an
      evolutionary-designed frequency-coding mechanism that, in turn, facilitates
      Bayesian reasoning. The nested-sets account predicts a null iconicity effect,
      because iconicity does not affect the salience of a nested-sets structure-the
      factor facilitating Bayesian reasoning processed by a general reasoning
      mechanism. In two well-powered experiments (N = 577), we found no support for a
      positive iconicity effect across different iconicity levels that were manipulated
      in different visual displays (meta-analytical overall effect: log OR = -0.13, 95%
      CI [-0.53, 0.28]). A Bayes factor analysis provided strong evidence in favor of
      the null hypothesis-the null iconicity effect. Thus, these findings corroborate
      the nested-sets rather than the ecological-rationality account of statistical
      reasoning.

PMID- 24307249
TI  - What counts as evidence for working memory training? Problems with correlated
      gains and dichotomization.
AB  - The question of whether computerized cognitive training leads to generalized
      improvements of intellectual abilities has been a popular, yet contentious, topic
      within both the psychological and neurocognitive literatures. Evidence for the
      effective transfer of cognitive training to nontrained measures of cognitive
      abilities is mixed, with some studies showing apparent successful transfer, while
      others have failed to obtain this effect. At the same time, several authors have
      made claims about both successful and unsuccessful transfer effects on the basis
      of a form of responder analysis, an analysis technique that shows that those who
      gain the most on training show the greatest gains on transfer tasks. Through a
      series of Monte Carlo experiments and mathematical analyses, we demonstrate that
      the apparent transfer effects observed through responder analysis are illusory
      and are independent of the effectiveness of cognitive training. We argue that
      responder analysis can be used neither to support nor to refute hypotheses
      related to whether cognitive training is a useful intervention to obtain
      generalized cognitive benefits. We end by discussing several proposed alternative
      analysis techniques that incorporate training gain scores and argue that none of
      these methods are appropriate for testing hypotheses regarding the effectiveness
      of cognitive training. 

PMID- 24307250
TI  - The eyes grasp, the hands see: metric category knowledge transfers between vision
      and touch.
AB  - Categorization of seen objects is often determined by the shapes of objects.
      However, shape is not exclusive to the visual modality: The haptic system also is
      expert at identifying shapes. Hence, an important question for understanding
      shape processing is whether humans store separate modality-dependent shape
      representations, or whether information is integrated into one multisensory
      representation. To answer this question, we created a metric space of computer
      generated novel objects varying in shape. These objects were then printed using a
      3-D printer, to generate tangible stimuli. In a categorization experiment,
      participants first explored the objects visually and haptically. We found that
      both modalities led to highly similar categorization behavior. Next, participants
      were trained either visually or haptically on shape categories within the metric
      space. As expected, visual training increased visual performance, and haptic
      training increased haptic performance. Importantly, however, we found that visual
      training also improved haptic performance, and vice versa. Two additional
      experiments showed that the location of the categorical boundary in the metric
      space also transferred across modalities, as did heightened discriminability of
      objects adjacent to the boundary. This observed transfer of metric category
      knowledge across modalities indicates that visual and haptic forms of shape
      information are integrated into a shared multisensory representation. 

PMID- 24307251
TI  - Transcriptional regulatory network and protein-protein interaction to reveal the
      mechanism of pancreatic cancer.
AB  - The development of pancreatic cancer (PC) may involve the over-expression of
      oncogenes, inactivation tumor suppressor genes or the deregulation of various
      signaling proteins. Thus identification and analysis of transcriptional
      regulatory relationship as well as protein-protein interaction (PPI) in PC to
      provide deep insights into the pathogenetic mechanism of pancreatic cancer. In
      this study, we downloaded the gene expression profile of PC from Gene Expression
      Omnibus and identified differentially expressed genes (DEGs) in PC patients
      compared with controls. To further understand how these DEGs act together to
      account for the initiation of pancreatic cancer, a transcriptional regulatory
      network was constructed to find the notes for GO function and KEGG pathways
      annotation, aiming to explore the clusters and pathways in PC. A total of 1,821
      transcriptional regulatory relationships were identified. Then, a PPI network was
      constructed and noted by GO and KEGG, and some special modules, clusters and
      pathways were identified to involved in PC. Finally, we constructed the
      transcriptional regulatory network and PPI network of pancreatic cancer.
      Comparing the pathways involved in Transcriptional regulatory network and PPI
      network, pathway in cancer, PC, p53 signaling pathway, Hematopoietic cell lineage
      and graft-versus-host disease co-existed in these two network, so we predict
      these pathways may play key factors in development of cancer. 

PMID- 24307252
TI  - Characterization of a glutamine synthetase gene DvGS1 from Dunaliella viridis and
      investigation of the impact on expression of DvGS1 in transgenic Arabidopsis
      thaliana.
AB  - A novel glutamine synthetase (GS) gene DvGS1 showing highest amino acid sequence
      identity of 78 % with the other homologous GS proteins from green algae, was
      isolated and characterized from Dunaliella viridis. Phylogenetic analysis
      revealed that DvGS1 occupied an independent phylogenetic position which was
      different with the GSs from higher plants, animals and microbes. Functional
      complement in E. coli mutant confirmed that the DvGS1 encoded functional GS
      enzyme. Real-time PCR analysis of DvGS1 in D. viridis cells under nitrogen
      starvation revealed that the mRNA level of DvGS1 was positively up-regulated in
      12 h. The DvGS1 levels at the points of 12 and 24 h were separately twofold and
      fourfold of the level before nitrogen starvation. In order to investigate the
      potential application of DvGS1 in higher plants, the transgenic study of DvGS1 in
      Arabidopsis thaliana was carried out. Phenotype identification demonstrated that
      all three transgenic lines of T3 generation showed obviously enhanced root length
      (26 %), fresh weight (22-46 % at two concentrations of nitrate supplies), stem
      length (26 %), leaf size (29 %) and silique number (30 %) compared with the wild
      type Arabidopsis. Biochemical analysis confirmed that all three transgenic lines
      had higher total nitrogen content, soluble protein concentration, total amino
      acid content and the leaf GS activity than the wild type plants. The free NH4 (+)
      and NO3 (-) concentration in fresh leaves of three transgenic lines were reduced
      by 17-26 % and 14-15 % separately (at two concentrations of nitrate supplies)
      compared with those of the wild types. All the results indicated that over
      expression of DvGS1 in Arabidopsis significantly results in the improvement of
      growth phenotype and the host's nitrogen use efficiency.

PMID- 24307253
TI  - Identification of a novel fumarase C from Streptomyces lividans TK54 as a good
      candidate for L-malate production.
AB  - Fumarase is a key enzyme that catalyzes the reversible hydration of fumarate to L
      malate in the tricarboxylic acid cycle. This reaction has been extensively
      utilized for industrial applications in producing L-malate. In this study, a
      fumarase C gene from Streptomyces lividans TK54 (slFumC) was cloned and expressed
      as a fused protein (SlFumC) in Escherichia coli. The molecular mass of SlFumC was
      about 49 kDa determined by SDS-PAGE. Kinetic studies showed that the K m value of
      SlFumC for L-malate increased by approximately 8.5-fold at pH 6.5 (6.7 +/- 0.81
      mM) to 8.0 (57.0 +/- 1.12 mM), which was higher than some known fumarases. The
      catalytic efficiency (k cat) and the specific activity increased by about 9.5
      fold at pH 6.5 (65 s(-1)) to 8.0 (620 s(-1)) and from 79 U/mg at pH 6.5 to 752
      U/mg at pH 8.0, respectively. Therefore, SlFumC may acquire strong catalytic
      ability by increasing pH to partially compensate for the loss of substrate
      affinity. The enzyme also showed substrate inhibition phenomenon, which is pH
      dependent. Specific activity of SlFumC was gradually enhanced with increasing
      phosphate concentrations. However, no inhibition was observed at high
      concentration of phosphate ion, which was distinctly different in case of other
      Class II fumarases. In industrial process, the reaction temperatures for L-malate
      production are usually set between 40 and 60  degrees C. The recombinant SlFumC
      displayed maximal activity at 45  degrees C and remained over 85 % of original
      activity after 48 h incubation at 40  degrees C, which was more thermostable than
      other fumarases from Streptomyces and make it an efficient enzyme for use in the
      industrial production of L-malate.

PMID- 24307254
TI  - Management of children in the deployed intensive care unit at Camp Bastion,
      Afghanistan.
AB  - BACKGROUND: The deployed Intensive Therapy Unit (ITU) in the British military
      field hospital in Camp Bastion, Afghanistan, admits both adults and children. The
      purpose of this paper is to review the paediatric workload in the deployed ITU
      and to describe how the unit copes with the challenge of looking after critically
      injured and ill children. METHODS: Retrospective review of patients <16 years of
      age admitted to the ITU in the British military field hospital in Camp Bastion,
      Afghanistan, over a 1-year period from April 2011 to April 2012. RESULTS: 112/811
      (14%) admissions to the ITU were paediatric (median age 8 years, IQR 6-12, range
      1-16). 80/112 were trauma admissions, 13 were burns, four were non-trauma
      admissions and 15 were readmissions. Mechanism of injury in trauma was blunt in
      12, blast (improvised explosive device) in 45, blast (indirect fire) in seven and
      gunshot wound in 16. Median length of stay was 0.92 days (IQR 0.45-2.65). 82/112
      admissions (73%) were mechanically ventilated, 16/112 (14%) required inotropic
      support. 12/112 (11%) died before unit discharge. Trauma scoring was available in
      65 of the 80 trauma admissions. Eight had Injury Severity Score or New Injury
      Severity Score >60, none of whom survived. However, of the 16 patients with
      predicted mortality >50% by Trauma Injury Severity Score, seven survived. Seven
      cases required specialist advice and were discussed with the Birmingham
      Children's Hospital paediatric intensive care retrieval service. The mechanisms
      by which the Defence Medical Services support children admitted to the deployed
      adult ITU are described, including staff training in clinical, ethical and child
      protection issues, equipment, guidelines and clinical governance and rapid access
      to specialist advice in the UK. CONCLUSIONS: With appropriate support, it is
      possible to provide intensive care to children in a deployed military ITU.

PMID- 24307255
TI  - From the battlefield to the laboratory: the use of clinical data analysis in
      developing models of lower limb blast injury.
AB  - A key weapon in the insurgents' armamentarium against coalition and local
      security forces in Iraq and Afghanistan has been the use of anti-vehicle mines
      and improvised explosive devices (IEDs). Often directed against vehicle-borne
      troops, these devices, once detonated, transfer considerable amounts of energy
      through the vehicle to the occupants. This results in severe lower limb injuries
      that are frequently limb threatening. Fundamental to designing novel mitigation
      strategies is a requirement to understand the injury mechanism by developing
      appropriate injury modelling tools that are underpinned by the analysis of
      contemporary battlefield casualty data. This article aims to summarise our
      understanding of the clinical course of lower limb blast injuries from IEDs and
      its value in developing unique injury modelling test-beds to evaluate and produce
      the next generation of protective equipment for reducing the devastating effects
      of blast injury. 

PMID- 24307257
TI  - A general multistage procedure for k-out-of-n gatekeeping.
AB  - We generalize a multistage procedure for parallel gatekeeping to what we refer to
      as k-out-of-n gatekeeping in which at least k out of n hypotheses ( 1 ? k ? n) in
      a gatekeeper family must be rejected in order to test the hypotheses in the
      following family. This gatekeeping restriction arises in certain types of
      clinical trials; for example, in rheumatoid arthritis trials, it is required that
      efficacy be shown on at least three of the four primary endpoints. We provide a
      unified theory of multistage procedures for arbitrary k, with k = 1 corresponding
      to parallel gatekeeping and k = n to serial gatekeeping. The theory provides an
      insight into the construction of truncated separable multistage procedures using
      the closure method. Explicit formulae for calculating the adjusted p-values are
      given. The proposed procedure is simpler to apply for this particular problem
      using a stepwise algorithm than the mixture procedure and the graphical procedure
      with memory using entangled graphs.

PMID- 24307258
TI  - Effect of combining conventional frying with radio-frequency post-drying on
      acrylamide level and quality attributes of potato chips.
AB  - BACKGROUND: In conventional manufacturing of potato chips, achieving an extremely
      low moisture content (2% by weight) in the final product necessitates prolonged
      exposure of potato slices to high oil temperatures. This promotes acrylamide
      formation and causes an exponential increase in acrylamide level toward the end
      of the frying process. In this regard, frying potato slices partially in hot oil
      followed by a radio-frequency (RF) drying treatment to selectively heat the
      remaining moisture appears to be a viable approach in terms of limiting
      acrylamide formation. RESULTS: RF post-drying of partially fried potato slices
      resulted in lower acrylamide levels (80.4 ng g(-1) for control, 59.4 ng g(-1) for
      RF post-dried potato slices partially fried for 95 s, 54.8 ng g(-1) for RF post
      dried potato slices partially fried for 80 s). This process modification also led
      a to 12% reduction in oil content in the final product. According to instrumental
      analysis results, RF post-dried samples had lower hardness and a slightly lower
      degree of browning in comparison to control. No significant difference (alpha =
      0.05) was found between samples in terms of sensory characteristics. CONCLUSION:
      Results demonstrate that RF post-processing may be an effective strategy for
      minimising acrylamide levels of potato chips without adversely affecting quality
      attributes.

PMID- 24307256
TI  - Hemostatic strategies for traumatic and surgical bleeding.
AB  - Wide interest in new hemostatic approaches has stemmed from unmet needs in the
      hospital and on the battlefield. Many current commercial hemostatic agents fail
      to fulfill the design requirements of safety, efficacy, cost, and storage.
      Academic focus has led to the improvement of existing strategies as well as new
      developments. This review will identify and discuss the three major classes of
      hemostatic approaches: biologically derived materials, synthetically derived
      materials, and intravenously administered hemostatic agents. The general class is
      first discussed, then specific approaches discussed in detail, including the
      hemostatic mechanisms and the advancement of the method. As hemostatic strategies
      evolve and synthetic-biologic interactions are more fully understood, current
      clinical methodologies will be replaced.

PMID- 24307259
TI  - Specialty, political affiliation, and perceived social responsibility are
      associated with U.S. physician reactions to health care reform legislation.
AB  - BACKGROUND: Little is known about how U.S. physicians' political affiliations,
      specialties, or sense of social responsibility relate to their reactions to
      health care reform legislation. OBJECTIVE: To assess U.S. physicians' impressions
      about the direction of U.S. health care under the Affordable Care Act (ACA),
      whether that legislation will make reimbursement more or less fair, and examine
      how those judgments relate to political affiliation and perceived social
      responsibility. DESIGN: A cross-sectional, mailed, self-reported survey.
      PARTICIPANTS: Simple random sample of 3,897 U.S.physicians. MAIN MEASURES: Views
      on the ACA in general, reimbursement under the ACA in particular, and perceived
      social responsibility. KEY RESULTS: Among 2,556 physicians who responded (RR2: 65
      %), approximately two out of five (41 %) believed that the ACA will turn U.S.
      health care in the right direction and make physician reimbursement less fair (44
      %). Seventy-two percent of physicians endorsed a general professional obligation
      to address societal health policy issues, 65 % agreed that every physician is
      professionally obligated to care for the uninsured or underinsured, and half (55
      %) were willing to accept limits on coverage for expensive drugs and procedures
      for the sake of expanding access to basic health care. In multivariable analyses,
      liberals and independents were both substantially more likely to endorse the ACA
      (OR 33.0 [95 % CI, 23.6-46.2]; OR 5.0 [95 % CI, 3.7-6.8], respectively), as were
      physicians reporting a salary (OR 1.7 [95 % CI, 1.2-2.5])or salary plus bonus (OR
      1.4 [95 % CI, 1.1-1.9)compensation type. In the same multivariate models, those
      who agreed that addressing societal health policy issues are within the scope of
      their professional obligations (OR 1.5 [95 % CI, 1.0-2.0]), who believe
      physicians are professionally obligated to care for the uninsured / under-insured
      (OR 1.7 [95 % CI,1.3-2.4]), and who agreed with limiting coverage for expensive
      drugs and procedures to expand insurance coverage (OR 2.3 [95 % CI, 1.8-3.0]),
      were all significantly more likely to endorse the ACA. Surgeons and procedural
      specialists were less likely to endorse it (OR 0.5 [95 % CI, 0.4-0.7], OR 0.6 [95
      %CI, 0.5-0.9], respectively). CONCLUSIONS: Significant subsets of U.S. physicians
      express concerns about the direction of U.S. health care under recent health care
      reform legislation. Those opinions appear intertwined with political
      affiliation,type of medical specialty, as well as perceived social
      responsibility.

PMID- 24307260
TI  - Variation in the risk of readmission among hospitals: the relative contribution
      of patient, hospital and inpatient provider characteristics.
AB  - BACKGROUND: The risk of readmission varies among hospitals. This variation has
      led the Centers of Medicare and Medicaid services to reduce payments to hospitals
      with excess readmissions. The contribution of patient characteristics, hospital
      characteristics and provider type to the variation in risk of readmission among
      hospitals has not been determined. OBJECTIVE: To describe the variation in risk
      of readmission among hospitals and partition it by patient characteristics,
      hospital characteristics and provider type. DESIGN: Retrospective research design
      of 100% Texas Medicare data using multilevel, multivariable models. SUBJECTS: A
      total of 514,064 admissions of Medicare beneficiaries to 272 hospitals in Texas
      for medical diagnoses during the years 2008 and 2009. MAIN MEASURES: Using
      hierarchical generalized linear models, we describe the hospital-specific
      variation in risk of readmission that is attributable to patients
      characteristics, hospital characteristics and provider type by measuring the
      variance and intraclass correlation coefficients. KEY RESULTS: Of the total
      variation in risk of readmission, only a small amount (0.84%) is attributed to
      hospitals. In further analyses modeling the components of this variation among
      hospitals, differences in patient characteristics in the hospitals explained
      56.2% of the variation. Hospital characteristics and the type of provider
      explained 9.3% of the variation among hospitals and 0.08% of the total variation
      in risk of readmission. CONCLUSIONS: Patient characteristics are the largest
      contributor to variation in risk of readmission among hospitals. Measurable
      hospital characteristics and the type of inpatient provider contribute little to
      variation in risk of readmission among hospitals.

PMID- 24307261
TI  - Reduction in 18F-fluorodeoxyglucose uptake on serial cardiac positron emission
      tomography is associated with improved left ventricular ejection fraction in
      patients with cardiac sarcoidosis.
AB  - BACKGROUND: Cardiac positron emission tomography (PET) using (18)F
      fluorodeoxyglucose (FDG) has been used to diagnose and monitor cardiac
      sarcoidosis (CS). It is not known whether a reduction in myocardial inflammation,
      as measured by FDG uptake, is associated with improvement in LV ejection fraction
      (EF). METHODS: For 23 patients with CS followed by a total of 90 serial PET exams
      (median 4 per patient), two physicians blinded to EF quantified the maximum of
      standardized uptake value (SUV) and volume of inflamed tissue above two distinct
      thresholds to assess the intensity and extent of FDG uptake on each study. Using
      gated (82)Rubidium rest myocardial perfusion images, EF was measured blinded to
      all clinical and FDG data. To account for clustering and differences in scan
      frequency, a longitudinal mixed effects model was used to evaluate the
      relationship between FDG uptake and changes in EF on interval scans. RESULTS:
      Among 23 patients with serial PET exams (mean age 49, 74% male, mean baseline EF
      43% +/- 13%), the median time between the first and last scan was 2.0 years.
      Overall, 91% were treated with corticosteroids, 78% with ACE/ARB, 83% with beta
      blockers, and 83% had ICDs. Longitudinal regression demonstrated a significant
      inverse linear relationship between maximum SUV and EF with an expected increase
      in EF of 7.9% per SUV reduction of 10 g.mL(-1) (P = .008). Likewise, in an
      analysis based on volume, there was an increase in EF of 2.1% per 100 cm(3)
      decrease in volume of inflamed tissue using a threshold of 2.7 g.mL(-1) (P =
      .028) and an increase in EF of 3.8% per 100 cm(3) decrease (P = .022) using a SUV
      threshold of 4.1 g.mL(-1). CONCLUSIONS: In a longitudinal cohort of CS patients,
      a reduction in the intensity and extent of myocardial inflammation on FDG PET is
      associated with improvement in EF. These data suggest serial PET scanning may
      help guide titration of immunosuppressive therapy to improve or prevent heart
      failure in CS.

PMID- 24307262
TI  - Delayed sodium 18F-fluoride PET/CT imaging does not improve quantification of
      vascular calcification metabolism: results from the CAMONA study.
AB  - BACKGROUND: This study aimed to determine if delayed sodium (18)F-fluoride
      (Na(18)F) PET/CT imaging improves quantification of vascular calcification
      metabolism. Blood-pool activity can disturb the arterial Na(18)F signal. With
      time, blood-pool activity declines. Therefore, delayed imaging can potentially
      improve quantification of vascular calcification metabolism. METHODS AND RESULTS:
      Twenty healthy volunteers and 18 patients with chest pain were prospectively
      assessed by triple time-point PET/CT imaging at approximately 45, 90, and 180
      minutes after Na(18)F administration. For each time point, global uptake of
      Na(18)F was determined in the coronary arteries and thoracic aorta by calculating
      the blood-pool-corrected maximum standardized uptake value (cSUV(MAX)). A target
      to-background ratio (TBR) was calculated to determine the contrast resolution at
      45, 90, and 180 minutes. Furthermore, we assessed whether the acquisition time
      point affected the relation between cSUV(MAX) and the estimated 10-year risk for
      fatal cardiovascular disease (SCORE %). Coronary cSUV(MAX) (P = .533) and aortic
      cSUV(MAX) (P = .654) remained similar with time, whereas the coronary TBR (P <
      .0001) and aortic TBR (P < .0001) significantly increased with time. Even though
      the contrast resolution improved with time, positive correlations between SCORE %
      and coronary cSUV(MAX) (P < .020) and aortic cSUV(MAX) (P < .005) were observed
      at all investigated time points. CONCLUSIONS: Delayed Na(18)F PET/CT imaging does
      not improve quantification of vascular calcification metabolism. Although
      contrast resolution improves with time, arterial Na(18)F avidity is invariant to
      the time between Na(18)F administration and PET/CT acquisition. Therefore, the
      optimal PET/CT acquisition time-point to quantify vascular calcification
      metabolism is achieved as early as 45 minutes after Na(18)F administration.

PMID- 24307263
TI  - Application of two-dimensional gel-based mass spectrometry to functionally
      dissect resistance to targeted cancer therapy.
AB  - PURPOSE: The majority of gastric cancers are diagnosed at advanced stages,
      characterized by robust therapy resistance. The oncoprotein hypoxia-inducible
      factor 1 (HIF-1) is associated with therapy resistance, partly via activation of
      the DNA damage response. We have noted a robust ability of gastric cancer cells
      to functionally compensate the loss of HIF-1 in vitro. The purpose of this study
      was to identify molecular pathways that underlie this compensation. EXPERIMENTAL
      DESIGN: We performed 2DE to compare the nuclear proteome of wild-type and HIF-1
      deficient gastric cancer cells. Differently expressed protein spots were
      identified via MS). After bioinformatic evaluation, functional validation of
      selected identified pathways was performed. RESULTS: 2DE displayed a total of
      2523 protein spots, from which 87 were identified as regulated by HIF-1. Seventy
      of the identified spots were different proteins and 17 were isoforms.
      Bioinformatic analyses revealed that a significant amount of the identified
      proteins were related to cellular survival pathways. Specifically, members of the
      proteasome pathway were found upregulated upon loss of HIF-1. Combined inhibition
      of HIF-1 and the proteasome inflicted significant DNA damage, supporting the
      hypothesis that the proteasome is of functional importance to compensate the loss
      of HIF-1. CONCLUSIONS AND CLINICAL RELEVANCE: Our data show robust and functional
      changes of the nuclear proteome upon inactivation of the HIF-1 oncoprotein in
      gastric cancer cells. We propose that 2DE-MS represents a useful tool to
      functionally dissect resistance mechanisms to targeted therapy and to identify
      novel targets for antiproliferative combination therapy.

PMID- 24307264
TI  - Combination of ATRA and ATRC for the synthesis of periodic vinyl copolymers.
AB  - A new approach to periodic vinyl copolymers via combination of atom transfer
      radical addition (ATRA) and atom transfer radical coupling (ATRC) is reported.
      The two examples are methyl methacrylate (MMA) and styrene (St) periodic
      copolymer (P(SMMS)) and acrylonitrile (AN) and St periodic copolymer (P(SAAS)).
      First, two monomer sequence units (MSU) with built-in sequence, SMMS and SAAS,
      are synthesized through the controlled ATRA of two ATRP initiators with St. Then,
      the ATRC of SMMS and SAAS are conducted at high radical conditions to generate
      two types of high-molecular-weight copolymers, P(SMMS) and P(SAAS). Though side
      reactions can not be totally avoided, characterizations of the polymer structure
      with a variety of means confirm that the main chain structures of P(SMMS) and
      (PSAAS) are predominantly with the periodic sequences from the MSUs. Attempts to
      suppress the side reactions are successful via the MNP-mediated ATRC of SMMS and
      SAAS. 

PMID- 24307265
TI  - c-Met inhibition in a HOXA9/Meis1 model of CN-AML.
AB  - BACKGROUND: Hematopoiesis is a paradigm for developmental processes,
      hierarchically organized, with stem cells at its origin. Hematopoietic stem cells
      (HSCs) replenish progenitor and precursor cells of multiple lineages, which
      normally differentiate into short-lived mature circulating cells. Hematopoiesis
      has provided insight into the molecular basis of tissue homeostasis and
      malignancy. Malignant hematopoiesis, in particular acute myeloid leukemia (AML),
      results from impaired development or differentiation of HSCs and progenitors. Co
      overexpression of HOX and TALE genes, particularly the HOXA cluster and MEIS1, is
      associated with AML. Clinically relevant models of AML are required to advance
      drug development for an aging patient cohort. RESULTS: Molecular analysis
      identified altered gene, microRNA, and protein expression in HOXA9/Meis1 leukemic
      bone marrow compared to normal controls. A candidate drug screen identified the c
      Met inhibitor SU11274 for further analysis. Altered cell cycle status, apoptosis,
      differentiation, and impaired colony formation were shown for SU11274 in AML cell
      lines and primary leukemic bone marrow. CONCLUSIONS: The clonal HOXA9/Meis1 AML
      model is amenable to drug screening analysis. The data presented indicate that
      human AML cells respond in a similar manner to the HOXA9/Meis1 cells, indicating
      pre-clinical relevance of the mouse model.

PMID- 24307266
TI  - Alignment-free three-dimensional optical metamaterials.
AB  - Three-dimensional optical metamaterials based on multilayers typically rely on
      critical vertical alignment to achieve the desired functionality. Here the
      conditions under which three-dimensional metamaterials with different
      functionalities may be realized without constraints on alignment are analyzed and
      demonstrated experimentally. This study demonstrates that the release of
      alignment constraints for multilayered metamaterials is allowed, while their
      anomalous interaction with light is preserved. 

PMID- 24307267
TI  - Vacuum assisted closure therapy for treatment of complex wounds in replanted
      extremities.
AB  - The object of this study was to compare the outcomes of the vacuum assisted
      closure (VAC) therapy and conventional wound care with dressing change for
      treatment of complex wounds in patients with replantation of amputated upper and
      lower extremities. Data of 43 patients with replantation of amputated extremities
      from May 2004 to December 2011 were reviewed. There were 18 wounds of 18 patients
      with replantation, which were treated by dressing change and 26 wounds of 25
      patients by VAC therapy. The outcomes were evaluated by the survival rate of
      replanted extremities, growth of granulation tissue, interval between wound
      treatment and secondary procedure and eventual secondary wound coverage methods.
      Vascular thromboses were found in 3 patients with wound treatment by dressing
      change and 5 by VAC. All replants of two groups of patients survived after
      salvage procedures. The wound score was 3.6 +/- 0.7 in the conventional dressing
      change group and 5.8 +/- 0.7 in the VAC group at the sixth day after treatment,
      respectively. The intervals between wound treatment and secondary wound coverage
      procedure were 12.0 +/- 1.7 days in the dressing change group and 6.1 +/- 0.7
      days in the VAC group. Flaps were applied for wound coverage in 9 out of 18
      (50.0%) wounds in the dressing change group and 5 out of 26 (19.2%) in the VAC
      group (P < 0.05), when the wounds of rest of patients were covered by the skin
      graft. The results showed that VAC could promote the growth of granulation tissue
      of wound, decrease the need of flap for wound coverage, and did not change the
      survival of replantation.

PMID- 24307268
TI  - Alcohol drinking and second primary cancer risk in patients with upper
      aerodigestive tract cancers: a systematic review and meta-analysis of
      observational studies.
AB  - BACKGROUND: We conducted a systematic review and meta-analysis of existing data
      from observational studies to assess the strength of the association of alcohol
      drinking with second primary cancer risk in patients with upper aerodigestive
      tract (UADT; oral cavity, pharynx, larynx, and esophagus) cancer. METHODS: PubMed
      and Embase were searched up to July 2012 and the reference lists of studies
      included in the analysis were examined. Random-effects models were used to
      estimate summary relative risks (RR) and 95% confidence interval (CI). RESULTS:
      Nineteen studies, 8 cohort and 11 case-control studies, were included. In highest
      versus lowest meta-analyses, alcohol drinking was associated with significantly
      increased risk of UADT second primary cancers (RR, 2.97; 95% CI, 1.96-4.50).
      Significantly increased risks were also observed for UADT and lung combined (RR,
      1.90; 95% CI, 1.16-3.11) and all sites (RR, 1.60; 95% CI, 1.22-2.10) second
      primary cancers. For an increase in the alcohol intake of 10 grams per day, dose
      response meta-analysis resulted in a significantly increased RR of 1.09 (95% CI,
      1.04-1.14) for UADT second primary cancers. CONCLUSIONS: Alcohol drinking in
      patients with UADT cancer is associated with an increased risk of second primary
      cancers. Studies conducted in alcohol drinking patients with UADT cancer and
      evaluating the effect of alcohol cessation on second primary cancer and other
      outcomes are needed. IMPACT: Our results emphasize the importance of prevention
      policies aiming to reduce alcohol drinking. Health-care professionals should
      encourage alcohol drinking patients with UADT cancer to reduce their consumption
      and reinforce the surveillance of this at-risk subpopulation.

PMID- 24307269
TI  - Bioequivalence of two pregabalin 300 mg capsules (Neurexal and Lyrica(r)) in
      healthy human volunteers.
AB  - The pharmacokinetics of 2 brands of pregabalin 300 mg capsules were compared in
      23 healthy human volunteers after a single oral dose in a randomized cross-over
      study. The study protocol was prepared with relevance to the requirements set in
      the US FDA and the EMA guidances for conduction of bioequivalence studies.
      Reference (Lyrica((r)), Pfizer, France) and test (Neurexal, Pharmaline, Lebanon)
      products were administered to fasted volunteers. Blood samples were collected up
      to 48 h and assayed for pregabalin using a validated LC-MS/MS method. The
      pharmacokinetic parameters AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2 and
      elimination rate constant were determined from plasma concentration-time profile
      by non-compartmental analysis method using WinNonlin V5.2. The analysis of
      variance did not show any significant difference between the 2 formulations and
      90% confidence intervals fell within the acceptable range for bioequivalence: 80
      125%. It was concluded that the 2 brands exhibited comparable pharmacokinetic
      profiles and that Pharmaline's Neurexal is bioequivalent to Lyrica((r)) of
      Pfizer, France.

PMID- 24307270
TI  - The inhibition of monoamine oxidase by phenformin and pentamidine.
AB  - A computational study has suggested that phenformin, an oral hypoglycaemic drug,
      may bind to the active sites of the monoamine oxidase (MAO) A and B enzymes. The
      present study therefore investigates the MAO inhibitory properties of phenformin.
      Pentamidine, a structurally related diamidine compound, has previously been
      reported to be a MAO inhibitor and was included in this study as a reference
      compound. Using recombinant human MAO-A and MAO-B, this study finds that
      phenformin acts as a moderately potent MAO-A selective inhibitor with an IC50
      value of 41 uM. Pentamidine, on the other hand, potently inhibits both MAO-A and
      MAO-B with IC50 values of 0.61 MUM and 0.22 MUM, respectively. An examination of
      the recoveries of the enzymatic activities after dilution and dialysis of the
      enzyme-inhibitor complexes shows that both compounds interact reversibly with the
      MAO enzymes. A kinetic analysis suggests that pentamidine acts as a competitive
      inhibitor with estimated Ki values of 0.41 MUM and 0.22 MUM for the inhibition of
      MAO-A and MAO-B, respectively. Phenformin also exhibited a competitive mode of
      MAO-A inhibition with an estimated Ki value of 65 uM. This study concludes that
      biguanide and amidine functional groups are most likely important structural
      features for the inhibition of the MAOs by phenformin and pentamidine, and
      compounds containing these and closely related functional groups should be
      considered as potential MAO inhibitors. Furthermore, the biguanide and amidine
      functional groups may act as useful moieties in the future design of MAO
      inhibitors.

PMID- 24307271
TI  - Study of antimicrobial effects of vancomycin loaded PLGA nanoparticles against
      enterococcus clinical isolates.
AB  - Researchers have demonstrated that antimicrobial agents in nanoparticle (NP)
      forms have better activities. Vancomycin (VCM), as a glycopeptide antibiotic with
      antimicrobial activity against gram positive bacteria, is poorly absorbed from
      the intestinal tract. Enterococcus is a genus of bacteria that became resistant
      to a wide range of antibiotics in last decades, and cause severe infections in
      hospitalized patients. This paper describes preparation of VCM--loaded poly
      (lactic-co-glycolic acid) (PLGA) NPs and compares the antimicrobial effects with
      drug solution against clinical Enterococcus isolates. VCM-loaded PLGA NPs were
      fabricated by W1/O/W2 solvent evaporation method. The comparison of obtained
      Minimum Inhibitory Concentration (MIC) values showed a significant decrease in
      the antimicrobial effect of VCM -loaded NPs. Results also indicated that the
      potency of the NPs against VCM resistant isolates of Enterococcus was less than
      VCM susceptible isolates. The reduced antimicrobial effect of formulated NPs in
      invitro condition is perhaps related to the strong electrostatic linkage between
      hydrophilic drug (VCM) and hydrophobic polymer (PLGA) that lead to the slow
      release of the antibiotic from polymeric NPs.

PMID- 24307272
TI  - Isolation and characterization of DNA topoisomerase II from cauliflower
      inflorescences.
AB  - Type II DNA topoisomerase has been isolated from inflorescences of cauliflower
      (Brassica oleracea var. botrytis) through a sequence of polyethylene glycol
      fractionation, ammonium sulfate precipitation, and column chromatography on CM
      Sephadex, hydroxyapatite and phosphocellulose. The molecular weight of the native
      enzyme, based on sedimentation coefficient (9S) and gel filtration analysis
      (Stokes radius, 60 A), was estimated to be 223 000. This enzyme was able to
      catalyze fully the relaxation of supercoiled DNA by breaking and then rejoining
      the double-stranded DNA. The breaking reaction was reversible by a change in salt
      concentrations. When an antitumor drug, 4'-(9-acridinylamino)-methanesulfon-m
      anisidide, was added to the topoisomerase reaction, DNA cleavage fragments were
      accumulated; and this suggested that the drug interfered with the reaction at the
      rejoining step. This enzyme also catalyzed the formation of DNA catenanes in the
      presence of 8% polyethylene glycol or histone H1, while few catenanes were formed
      in the presence of spermidine, which was highly effective on a bacterial enzyme. 

PMID- 24307273
TI  - Changes with time in the distribution of virus and PR protein around single local
      lesions of TMV infected tobacco.
AB  - ELISA was used to determine PR la protein and TMV accumulation in local necrotic
      lesions produced on salicylic acid and water sprayed Nicotiana tabacum cv Xanthi
      nc leaves. The amount of PR la protein produced is the result of an interaction
      between the salicylic acid treatment and lesion growth. The implication of these
      observations for experiments investigating the relationship between PR proteins
      and resistance are discussed.The distribution of TMV and PR la protein in and
      around single local necrotic lesions up to 14 days after inoculation was measured
      by ELISA. The highest concentration of TMV was in the centre of the lesion and
      decreased rapidly with distance from the centre. In contrast there was very
      little PR la protein in the centre of the lesion, the largest amounts were just
      outside the centre, and the concentration then decreased with distance from the
      centre. This is the distribution that might be expected for a substance closely
      associated with the restriction of virus spread. 

PMID- 24307274
TI  - Characterization of photosystem II mutants of Chlamydomonas reinhardii lacking
      the psbA gene.
AB  - We have examined 78 chloroplast mutants of Chlamydomonas reinhardii lacking
      photosystem II activity. Most of them are unable to synthesize the 32 Kdalton
      protein. Analysis of 22 of these mutants reveals that they have deleted both
      copies of the psbA gene (which codes for the 32 Kdalton protein) in their
      chloroplast genome. Although these mutants are able to synthesize and to
      integrate the other photosystem II polypeptides in the thylakoid membranes, they
      are unable to assemble a stable functional photosystem II complex. The 32
      Kprotein appears therefore to play an important role not only in photosystem II
      function, but also in stabilizing this complex. 

PMID- 24307275
TI  - Isolation and characterization of cDNAs encoding oat 12S globulin mRNAs.
AB  - A cDNA library was made from poly(A(+)) RNA isolated from developing oat seeds,
      and oat globulin cDNA clones were identified by hybridization with synthetic
      oligonucleotides. Globulin clones were characterized by restriction enzyme
      mapping and cross-hybridization analysis. Based on these comparisons, four
      classes of globulin clones were distinguished. These clones hybridized to
      multiple DNA fragments in restriction enzyme digests of oat genomic DNA,
      indicating that the genes exist in a multigene family. The nucleotide sequence of
      one of the globulin cDNA clones was determined. The amino acid sequence derived
      from the DNA sequence verified its identity as an oat globulin and confirmed that
      the protein is synthesized as a precursor similar to legume 11S storage
      globulins. The basic polypeptide encoded at the 3' end of the mRNA was found to
      be homologous to the basic polypeptides of other 11S seed globulins. 

PMID- 24307276
TI  - Chloroplast genome organisation in sugar beet and maize.
AB  - The XhoI and SmaI restriction map of the chloroplast genome from the fertile
      cytoplasm of sugar beet has been constructed from overlapping cosmid clones. The
      genome was found to be typical of that of a dicotyledonous species, being 147.3
      kb in size and having an inverted repeat. RbcL for the large subunit of ribulose
      1,5-bisphosphate carboxylase, psbA for the 32 kD protein of the photosystem II
      reaction centre, and the 16S ribosomal RNA were located using heterologous
      probes. In both sugar beet and maize the inverted repeats recombine giving two
      isomeric forms of the genome. 

PMID- 24307277
TI  - Site-specific mutagenesis of potato spindle tuber viroid cDNA: : Alterations
      within premelting region 2 that abolish infectivity.
AB  - The infectivity of cloned viroid cDNAs permits investigation of
      structure/function relationships in these unusual pathogenic RNAs by systematic
      site-specific mutagenesis of the cDNAs and subsequent bioassay. We have used
      three different strategies to create nucleotide substitutions within premelting
      region 2, a region of potato spindle tuber viroid (PSTV) believed to be important
      in viroid replication: sodium bisulfitecatalyzed deamination of deoxycytosine
      residues, oligonucleotide-directed mutagenesis, and construction of chimeric
      viroid cDNAs from fragments of infectious PSTV and tomato apical stunt viroid
      cDNAs. Although their effects upon the rod-like native structure of PSTV should
      be minimal, C -> U transitions at positions 92 or 284 appeared to be lethal. When
      inoculation with PSTV cDNA containing a single nucleotide substitution was
      mediated by the Ti plasmid of Agrobacterium tumefaciens, PSTV progeny with an
      unaltered 'wild type' sequence was obtained. Two factors, the high error
      frequency characteristic of RNA synthesis and the use of a systemic bioassay for
      PSTV replication, may explain such sequence reversion and emphasize the
      importance of an appropriate bioassay system for screening mutant viroid cDNAs. 

PMID- 24307278
TI  - DNA sequences of tobacco chloroplast genes for tRNA(Ser) (GGA), tRNA (Thr) (UGU),
      tRNA (Leu) (UAA), tRNA (Phe) (GAA): the tRNA (Leu) gene contains a 503 bp intron.
AB  - The location and nucleotide sequence of tobacco chloroplast genes for tRNA(Ser)
      (GGA), tRNA(Thr) (UGU), tRNA(Leu) (UAA) and tRNA(Phe) (GAA) (trnS-GGA, trnT-UGU,
      trnL-UAA and trnF-GAA, respectively) have been determined. These genes are
      located in the 10 kbp BamHI fragment which lies in the middle of the large single
      copy region of the chloroplast DNA. The gene order is trnS-trnT-trnL-trnF. The
      trnS, trnL and trnF are encoded on the same strand while the trnT on the opposite
      strand. The trnL contains a 503 bp intron like maize and broad bean trnL-UAAs. 

PMID- 24307279
TI  - Parental attitudes toward newborn screening for Duchenne/Becker muscular
      dystrophy and spinal muscular atrophy.
AB  - INTRODUCTION: Disease inclusion in the newborn screening (NBS) panel should
      consider the opinions of those most affected by the outcome of screening. We
      assessed the level and factors that affect parent attitudes regarding NBS panel
      inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD),
      and spinal muscular atrophy (SMA). METHODS: The attitudes toward NBS for DMD,
      BMD, and SMA were surveyed and compared for 2 categories of parents, those with
      children affected with DMD, BMD, or SMA and expectant parents unselected for
      known family medical history. RESULTS: The level of support for NBS for DMD, BMD,
      and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among
      expectant parents. CONCLUSIONS: There was strong support for NBS for DMD, BMD,
      and SMA in both groups of parents. Given advances in diagnostics and promising
      therapeutic approaches, discussion of inclusion in NBS should continue.

PMID- 24307280
TI  - Sequence control in polymer chemistry through the Passerini three-component
      reaction.
AB  - A new strategy to achieve sequence control in polymer chemistry based on the
      iterative application of the versatile Passerini three-component reaction (P-3CR)
      in combination with efficient thiol-ene addition reactions is introduced. First,
      stearic acid was used as a starting substrate to build up a sequence-defined
      tetramer with a molecular weight of 1.6 kDa. Using an acid-functionalized PEG
      allowed for an easier isolation of the sequence-defined macromolecules by simple
      precipitation and led to a sequence-defined pentamer in a block-copolymer
      architecture. Importantly, this new strategy completely avoids protecting group
      chemistry. By following this strategy, a different side chain can be introduced
      to the polymer/oligomer backbone in a simple way and at a defined position within
      the macromolecule.

PMID- 24307281
TI  - Elevated level of fibrinogen increases caveolae formation; role of matrix
      metalloproteinase-9.
AB  - The role of the inflammatory agent fibrinogen (Fg) in increased pial venular
      permeability has been shown previously. It was suggested that an activation of
      matrix metalloproteinase-9 (MMP-9) is involved in Fg-induced enhanced
      transcytosis through endothelial cells (ECs). However, direct link between Fg,
      caveolae formation, and MMP-9 activity has never been shown. We hypothesized that
      at an elevated level, Fg enhances formation of functional caveolae through
      activation of MMP-9. Male wild-type (WT, C57BL/6J) or MMP-9 gene knockout (MMP9-/
      ) mice were infused with Fg (4 mg/ml, final blood concentration) or equal volume
      of phosphate buffered saline (PBS). After 2 h, mice were sacrificed and brains
      were collected for immunohistochemical analyses. Mouse brain ECs were treated
      with 4 mg/ml of Fg or PBS in the presence or absence of MMP-9 activity inhibitor,
      tissue inhibitor of metalloproteinases-4 (TIMP-4, 12 ng/ml). Formation of
      functional caveolae was assessed by confocal microscopy. Fg-induced increased
      formation of caveolae, which was defined by an increased co-localization of
      caveolin-1 (Cav-1) and plasmalemmal vesicle-associated protein-1 and was
      associated with an increased phosphorylation of Cav-1, was ameliorated in the
      presence of TIMP-4. These results suggest that at high levels, Fg enhances
      formation of functional caveolae that may involve Cav-1 signaling and MMP-9
      activation.

PMID- 24307282
TI  - Tumor-suppressing effects of miR-141 in human osteosarcoma.
AB  - Osteosarcoma is the most common primary malignancy to arise from bone. The
      pathogenesis of osteosarcoma is unclear, and new therapy molecular target is
      needed. The miRNAs researched suggested that miRNAs are involved in the
      pathogenesis of osteosarcoma. MiR-141, which belong to miR-200 family, take a
      part in tumorigenesis. However, the role of miR-141 in the pathogenesis of
      osteosarcoma remained unclear. In this study, we focused on the miR-141 in
      osteosarcoma and found that the expression of miR-141 is lower in osteosarcoma.
      Overexpression of miR-141 not only inhibits osteosarcoma cell proliferation but
      also induces cell apoptosis. It is estimated that miR-141 played its role via
      ZEB1 and ZEB2. In all, miR-141 played a osteosarcoma-suppressing role via ZEB1
      and ZEB2. Our finding may elucidate the miRNAs mechanism in osteosarcoma and
      provide a new molecule target for osteosarcoma therapy. 

PMID- 24307283
TI  - Change and significance of IL-8, IL-4, and IL-10 in the pathogenesis of terminal
      Ileitis in SD rat.
AB  - The objective of the study is to explore change and significance of IL-8, IL-4
      and IL-10 in the pathogenesis of terminal Ileitis in SD rat. 60 male SD rats were
      divided into model group, suture group, and control group equally. The rats
      subjected to ileum-cecum side-to-side anastomosis in terminal ileum in model
      group, suture in terminal ileum in suture group, and the control group accepted
      no special treatment. The terminal ileum tissue which was 1-3 cm from anastomotic
      stoma was collected at 2 and 8 weeks after surgery in each group. The
      pathological slice was observed under microscope, and PCR was applied to detect
      the expression of IL-4, IL-8, and IL-10 at different times. Pathological result
      showed that neutrophils significantly increased in model group and suture group
      at 2nd week, showing acute inflammatory reaction; model group showed chronic
      inflammation at 8th week. The change of IL-8, IL-4, and IL-10 expression level at
      2 weeks after surgery: The IL-8 expression level of SD rat terminal ileum tissue
      in model group was significantly higher than in control and suture groups (P <
      0.01), and it was higher in suture group compared to control group (P < 0.01);
      the expression level of IL-4 in control group was higher than model and suture
      groups (P < 0.05); there was no statistical significance between model group and
      suture group (P = 0.363); the expression level of IL-10 in control group was
      higher than in model and suture groups (P < 0.01), and it was higher in suture
      group compared to model group (P < 0.01). The change of IL-8, IL-4, IL-10
      expression level at 8 weeks after surgery: The expression level of IL-8
      significantly decreased in model group, and there was no significantly difference
      between three groups (P > 0.05); the expression level of IL-4 was higher in model
      group and suture group compared to 2nd week; there was no significance between
      three groups (P < 0.05); the expression of IL-10 was higher in model group
      compared to 2nd week (P < 0.01), it was lower than control group and suture group
      (P < 0.01); there was no significant difference between suture group and control
      group (P > 0.05). The chronic terminal ileum model could be successfully
      established by ileum-cecum side-to-side anastomosis in terminal ileum in SD rats;
      IL-8 can induce the inflammatory reaction in terminal ileitis and chemokines
      aggregation and mediate inflammatory reaction by mediating other inflammatory
      factors; as a proinflammatory cytokine, IL-8 can inhibit IL-10; IL-10 and IL-4
      can inhibit the inflammatory reaction of terminal ileum.

PMID- 24307285
TI  - B-cell modulation of dendritic-cell function: signals from the far side.
AB  - An appropriate immune response against a specific pathogen requires finely
      orchestrated interactions between the various cell populations within the immune
      system. At the same time, immunological tolerance to self must be maintained. DCs
      play an essential role in achieving these dual requisites. They coordinate
      adaptive immunity by integrating signals directly emanating from both infectious
      agents and cells of the immune system. Many such signals, especially those from
      innate cells and T cells, have been extensively characterized. In contrast,
      little is known about how B cells modulate function of DCs. B cells produce a
      variety of cytokines, including IL-10 and IL-6, which are known to influence DC
      function. In addition, Igs constitute the major secretory products of terminally
      differentiated B cells (plasma cells). DCs express various types of receptors for
      binding Ig, such as Fc receptors and C-type lectin receptors. In accordance, Igs
      can regulate DC function depending on the receptors engaged. Here, we review the
      emerging immunomodulatory role of cytokines and Ig secreted by B cells. We
      discuss the evidence for how these B-cell-derived factors may shape the adaptive
      immune response by directly acting on DCs.

PMID- 24307284
TI  - Unsuspected pyocyanin effect in yeast under anaerobiosis.
AB  - The blue-green phenazine, Pyocyanin (PYO), is a well-known virulence factor
      produced by Pseudomonas aeruginosa, notably during cystic fibrosis lung
      infections. It is toxic to both eukaryotic and bacterial cells and several
      mechanisms, including the induction of oxidative stress, have been postulated.
      However, the mechanism of PYO toxicity under the physiological conditions of
      oxygen limitation that are encountered by P. aeruginosa and by target organisms
      in vivo remains unclear. In this study, wild-type and mutant strains of the yeast
      Saccharomyces cerevisiae were used as an effective eukaryotic model to determine
      the toxicity of PYO (100-500 MUmol/L) under key growth conditions. Under respiro
      fermentative conditions (with glucose as substrate), WT strains and certain H2 O2
      -hypersensitive strains showed a low-toxic response to PYO. Under respiratory
      conditions (with glycerol as substrate) all the strains tested were significantly
      more sensitive to PYO. Four antioxidants were tested but only N-acetylcysteine
      was capable of partially counteracting PYO toxicity. PYO did not appear to affect
      short-term respiratory O2 uptake, but it did seem to interfere with cyanide
      poisoned mitochondria through a complex III-dependent mechanism. Therefore, a
      combination of oxidative stress and respiration disturbance could partly explain
      aerobic PYO toxicity. Surprisingly, the toxic effects of PYO were more
      significant under anaerobic conditions. More pronounced effects were observed in
      several strains including a 'petite' strain lacking mitochondrial DNA, strains
      with increased or decreased levels of ABC transporters, and strains deficient in
      DNA damage repair. Therefore, even though PYO is toxic for actively respiring
      cells, O2 may indirectly protect the cells from the higher anaerobic-linked
      toxicity of PYO. The increased sensitivity to PYO under anaerobic conditions is
      not unique to S. cerevisiae and was also observed in another yeast, Candida
      albicans. 

PMID- 24307286
TI  - Modular synthesis of triarylmethanes through palladium-catalyzed sequential
      arylation of methyl phenyl sulfone.
AB  - Triarylmethanes, which are valuable structures in materials, sensing and
      pharmaceuticals, have been synthesized starting from methyl phenyl sulfone as an
      inexpensive and readily available template. The three aryl groups were installed
      through two sequential palladium-catalyzed C-H arylation reactions, followed by
      an arylative desulfonation. This method provides a new synthetic approach to
      multisubstituted triarylmethanes using readily available haloarenes and aryl
      boronic acids, and is also valuable for the preparation of unexplored
      triarylmethane-based materials and pharmaceuticals.

PMID- 24307287
TI  - The occurrence and abundance of two alien eucalypt psyllids in apple orchards.
AB  - BACKGROUND: The arrival of alien insects is frequently associated with the
      introduction of alien plants. Two exotic Psylloidea native to Australia
      [Ctenarytaina eucalypti (Maskell, 1890) and Ctenarytaina spatulata Taylor, 1997]
      were recorded during a two-year survey in five apple orchards located in
      Asturias, on the northern coast of Spain. Both species develop on Eucalyptus, but
      our results suggest that the adults feed also on apple. RESULTS: The captures of
      adult Ctenarytaina, particularly C. spatulata (2191 individuals vs 100 of C.
      eucalypti) were higher than those of the psyllids that develop on apple. Both
      species occurred in all sites, including those most distant from the eucalypt
      plantations. Their abundance peaks matched with two crucial periods in the apple
      tree cycle: sprouting and leaf drop. The hypothesis that the adult eucalypt
      psyllids feed on apple is supported by the presence of a phytoplasma, the causal
      agent of the apple proliferation disease, in one specimen of each species. This
      phytoplasma can be only acquired after feeding on an infected apple tree. This is
      the first report of continuous captures of these psyllids in apple orchards.
      CONCLUSIONS: This study suggests that adults of the two Ctenarytaina species feed
      in apple orchards in Asturias.

PMID- 24307288
TI  - The concept of instability: a French perspective on the concept of ADHD.
AB  - Historical references to the emergence of the current concept of ADHD typically
      cite descriptions from medical textbooks by Weikard (1775) and Crichton (An
      inquiry into the nature and origin of mental derangement: Comprehending a concise
      system of the physiology and pathology of the human mind and a history of the
      passion and their affects. Cardell Jr and Davies, Londres, 1798) on attention
      disorders, poems of Hoffman on hyperactive and impulsive behaviors (Der
      Struwwelpeter. Frankfurt am Main, Literarische Anstalt, 1843), as well as the
      work of Still (Lancet 1:1008-1012, 1077-1082, 1163-1168, 1902a, Lancet
      159(4102):1008-1013, 1902b, Lancet 159(4103):1077-1082, 1902c, Lancet
      159(4104):1163-1168, 1902d) on impulsive behaviors and defective moral regulation
      of behavior. The notion of "instability" developed by French physicians between
      1887 and 1910 is rarely mentioned and often ignored. Writings from this period
      show that in France, the emergence of the concept of ADHD according to modern
      terminology comes from the notion of "mental instability" introduced in the 1890s
      under the leadership of Desire-Magloire Bourneville at the Hospital Bicetre in
      Paris, based on his observations of children and adolescents who had been labeled
      "abnormal" and placed in medical and educational institutions. In the early
      twentieth century, elaborating on the observations of Bourneville, Jean Phillipe
      and Georges Paul-Boncour showed the presence of a subgroup of "unstable" children
      who suffered from a disease entity in its own right within the population of
      "abnormal" schoolchildren (the terminology of the time). This new pathological
      entity included symptoms of hyperactivity, impulsivity and inattention,
      corresponding to today's classic triad of ADHD symptoms. While noting the lack of
      behavioral inhibition, clinical descriptions of Bourneville, Philip and Paul
      Boncour also considered the notion of "moral disorder" which at that time played
      an important role in psychopathology. This resulted in some degree of confusion
      between impulsive symptoms and major behavioral disturbances often associated
      with ADHD. 

PMID- 24307289
TI  - Monte Carlo simulation of in vivo Raman spectral measurements of human skin with
      a multi-layered tissue optical model.
AB  - Raman photon generation inside human skin and escaping to skin surface were
      modeled in an eight-layered skin optical model. Intrinsic Raman spectra of
      different skin layers were determined by microscopy measurements of excised skin
      tissue sections. Monte Carlo simulation was used to study the excitation light
      distribution and intrinsic Raman signal distortion caused by tissue reabsorption
      and scattering during in vivo measurements. The simulation results demonstrated
      how different skin layers contributed to the observed in vivo Raman spectrum.
      Using the strongest Raman peak at 1445 cm(-1) as an example, the simulation
      suggested that the integrated contributions of the stratum corneum layer is 1.3%,
      the epidermis layer 28%, the dermis layer 70%, and the subcutaneous fat layer
      1.1%. Reasonably good matching between the calculated spectrum and the measured
      in vivo Raman spectra was achieved, thus demonstrated great utility of our
      modeling method and approaches for help understanding the clinical measurements.

PMID- 24307290
TI  - Assessing fatigue in ankylosing spondylitis: the importance of frequency and
      severity.
AB  - OBJECTIVE: The aim of this study was to explore the value of assessing fatigue
      frequency and its relationship with fatigue severity in a UK cohort of AS
      patients. METHODS: Single items from the Evaluation of AS Quality of Life and
      BASDAI were used to measure fatigue frequency and severity, respectively. Items
      were included in a questionnaire containing AS-specific and generic measures,
      completed by participants in a postal survey at baseline and 6 months.
      Respondents were categorized at baseline into four groups according to fatigue
      frequency and severity and compared on other measures of health status. RESULTS:
      Of baseline responders who experienced fatigue (n = 451, 74%), 75% reported it to
      be frequent and severe, 15% frequent not severe and 10% severe not frequent.
      There was no difference between groups on gender, age or years with AS. Patients
      reporting frequent and severe fatigue had worse scores than other groups across
      all other health status measures. Patients reporting only frequent fatigue had
      similar scores to those reporting only severe fatigue, but worse than those
      without fatigue. Eighty-one per cent of non-fatigued patients and 79% of those
      with frequent and severe fatigue at baseline did not change their level of
      fatigue at 6 months. However, 80% of patients with frequent or severe fatigue at
      baseline changed, mainly to no fatigue (43%) or both frequent and severe fatigue
      (30%). CONCLUSION: Routinely assessing both the frequency and severity of fatigue
      is important in understanding the impact of fatigue and its change over time. Not
      assessing frequency could result in the failure to identify patients with
      significant fatigue. However, the multidimensional nature of fatigue should be
      further explored.

PMID- 24307291
TI  - Further confirmation that digital ulcers are associated with the severity of
      abnormality on nailfold capillaroscopy in patients with systemic sclerosis.

PMID- 24307292
TI  - Inflammatory plasma markers and risk for venous thromboembolism.
AB  - Venous thromboembolism (VTE) and arterial thrombosis have been thought to result
      from two different mechanisms. Recent data indicate that the two diseases may
      share some common risk factors, such as the activity of inflammation on
      haemostasis. In this population-based study we explored whether raised levels of
      inflammation-sensitive plasma markers (ISPs) increase the risk for venous
      thromboembolism. Measurements of five ISPs (fibrinogen, haptoglobin,
      ceruloplasmin, alpha1-antitrypsin and orosomucoid) were performed in 6,068
      subjects from "the Malmo Preventive Study". These apparently healthy men from the
      city of Malmo in Sweden, were included in the study between 1974 and 1982 and
      followed up until 2008. We calculated the hazard ratio (HR) for VTE in relation
      to the number of raised ISPs as well as individual ISPs in the fourth quartile.
      Mean follow-up time was 26.2 years. Out of the cohort (n = 6,068), 398 (6.6%) had
      a venous thromboembolism during the follow-up. The number of raised ISPs was
      significantly associated with age, BMI and smoking. Age, BMI and diabetes
      mellitus type 2 were also significant risk factors for developing a VTE (HR =
      1.05 with p < 0.01 and 95% CI 1.01-1.08, HR = 1.10 with p < 0.001 and 95% CI 1.06
      1.14 and HR = 1.78 with p < 0.05 and 95% CI 1.13-2.81, respectively). Incidence
      of venous thromboembolism was not significantly related to number of raised
      inflammatory proteins (p for trend = 0.37) or any of the individual ISPs. Age and
      BMI is significantly associated with the risk for developing VTE. Incidence of
      VTE was not associated with any of the inflammatory proteins.

PMID- 24307293
TI  - Developmental control of cortico-cerebral astrogenesis.
AB  - A remarkable body of research over the last 15 years has been aimed at
      disentangling the cellular and molecular mechanisms which regulate murine cortico
      cerebral astrogenesis. This research effort has allowed the reconstruction of the
      actual sizing of this process, as well as a better definition of its temporal,
      spatial and clonal articulation. Moreover, these investigations have shed
      substantial light on the cardinal molecular mechanisms governing the transition
      from pallial neuronogenesis to astrogenesis, as well as subsequent progress of
      the latter. It has turned out that proper temporal articulation of astrogenesis
      relies on a plethora of tightly interlaced mechanisms, which synergistically
      dampen astrogenesis prior to birth and promote it during peri- and postnatal
      life. The aim of this review is to provide a comprehensive and organic synthesis
      of these mechanisms, as well as a critical evaluation of their specific relevance
      to proper articulation of cerebral cortex astrogenesis in time and space. 

PMID- 24307294
TI  - Clonal analyses in the anterior pre-placodal region: implications for the early
      lineage bias of placodal progenitors.
AB  - Cranial ectodermal placodes, a vertebrate innovation, contribute to the
      adenohypophysis and peripheral nervous system of the head, including the paired
      sense organs (eyes, nose, ears) and sensory ganglia of the Vth, VIIth, IXth and
      Xth cranial nerves. Fate-maps of groups of cells in amphibians, teleosts and
      amniotes have demonstrated that all placodes have a common origin in a horseshoe
      shaped territory, known as the preplacodal region (PPR), which surrounds the
      presumptive neural plate of the late gastrula/early neurula stage embryo. Given
      the extensive regional overlap of progenitors for different placodes in the chick
      embryo, it has been a matter of debate as to whether individual cells in the PPR
      are truly multipotent progenitors, with regard to placodal identity, or rather
      are lineage-biased or restricted to a specific placodal type prior to overt
      differentiation. Utilizing clonal analyses in vivo, we demonstrate here that the
      anterior PPR comprises some precursors that contribute either to the olfactory or
      lens placode well before they are spatially segregated or committed to either of
      these placodal fates. This suggests that lineage bias towards a specific placodal
      fate may coincide with induction of the PPR. 

PMID- 24307295
TI  - Eph receptors and ephrin class B ligands are expressed at tissue boundaries in
      Hydra vulgaris.
AB  - Eph receptors and ephrins are important players in axon guidance, cell sorting
      and boundary formation. Both the receptors and the ligands are integrated
      transmembrane proteins and signalling is bidirectional. The prevalent outcome of
      signal transduction is repulsion of adjacent cells or cell populations.
      Eph/ephrins have been identified in all multicellular animals from human to
      sponge, their functions however appear to have been altered during evolution.
      Here we have identified four Eph receptors and three class B ligands in the
      cnidarian Hydra vulgaris, indicating that those are the evolutionary older ones.
      In situ hybridisation experiments revealed a striking complementarity of
      expression of receptors and ligands in tentacles and in developing buds. This
      suggests that the original function of ephrin signalling may have been in
      epithelial cell adhesion and the formation of tissue boundaries. 

PMID- 24307296
TI  - Xnr3 affects brain patterning via cell migration in the neural-epidermal tissue
      boundary during early Xenopus embryogenesis.
AB  - Neural induction and anteroposterior neural patterning occur simultaneously
      during Xenopus gastrulation by the inhibition of BMP and Wnt signaling,
      respectively. However, other processes might be necessary for determining the
      neural-epidermal boundary. Xenopus nodal-related-3 (Xnr3) is expressed in dorsal
      blastula and plays a role in neural formation. In this study, we analyzed how
      Xnr3 affects neural patterning to identify novel mechanisms of neural-epidermal
      boundary determination. In situ hybridization revealed that ventro-animal
      injection with Xnr3 shifted the lateral krox20 expression domain anteriorly and
      reduced Otx2 expression. The mature region of Xnr3 is necessary for these effects
      to occur, and the pro-region accelerated them. Phalloidin labeling revealed that
      cells around the neural-epidermal boundary lost their slender shape following
      Xnr3 injection. Moreover, we analyzed the cell migration of ectodermal cells and
      found specific Xnr3-induced effects at the neural-epidermal boundary. These
      findings together suggested that Xnr3 affects anterior ectoderm migration around
      the neural-epidermal boundary to induce a specific neural pattern abnormality.
      Change of the shape of surrounding ectodermal cells and the specific migratory
      pattern might therefore reflect the novel mechanism of neural-epidermal boundary.

PMID- 24307297
TI  - Long-term serial cultivation of mouse induced pluripotent stem cells in serum
      free and feeder-free defined medium.
AB  - Mouse embryonic stem (mES) cells and mouse induced pluripotent stem (miPS) cells
      are commonly maintained on inactivated mouse embryonic fibroblast feeder cells in
      medium supplemented with fetal bovine serum or proprietary replacements. An
      undefined medium containing unknown quantities of reagents has limited the
      development of applications for pluripotent cells because of the relative lack of
      knowledge regarding cell responses to differentiating growth factors. Therefore
      we developed a serum-free medium, designated ESF7, in which mES cells can be
      maintained in an undifferentiated state without feeder cells. The medium was
      tested for culturing miPS cells. The miPS cells have been maintained in ESF7
      medium for more than 3 years with an undifferentiated phenotype manifested by the
      expression of pluripotency marker genes and alkaline phosphatase, and these cells
      exhibited largely normal karyotypes. Furthermore, we found that fibroblast growth
      factor-2 (FGF-2) with heparin induced miPS cell differentiation into neuronal
      cells, both in an adherent monolayer and in embryoid body suspension culture.
      Moreover, we found that FGF-2 with bone morphogenetic protein 2 induced miPS cell
      differentiation into cardiomyocytes in embryoid body suspension culture.
      Furthermore, we transplanted subcutaneously miPS cells maintained in ESF7 into
      the dorsal flanks of SCID mice; all of the transplants produced tumors with
      tissues derived from all three embryonic germ layers. As this simple serum-free
      adherent monoculture system supports the long-term propagation of pluripotent iPS
      cells in vitro, it will allow us to elucidate cell responses to growth factors
      under defined conditions, and it should provide useful information for
      differentiation protocols for human iPS cells. 

PMID- 24307298
TI  - Pitx3 directly regulates Foxe3 during early lens development.
AB  - Pitx3 is a bicoid-related homeodomain transcription factor critical for the
      development of the ocular lens, mesencephalic dopaminergic neurons and skeletal
      muscle. In humans, mutations in PITX3 are responsible for cataracts and anterior
      segment abnormalities of varying degree; polymorphisms are associated with
      Parkinson?s disease. In aphakia (ak) mice, two deletions in the promoter region
      of Pitx3 cause abnormal lens development. Here, we investigated systematically
      the role of Pitx3 in lens development including its molecular targets responsible
      for the ak phenotype. We have shown that ak lenses exhibit reduced proliferation
      and aberrant fiber cell differentiation. This was associated with loss of Foxe3
      expression, complete absence of Prox1 expression, reduced expression of epsilon
      tubulin and earlier expression of gamma-crystallin during lens development. Using
      EMSA and ChIP assays, we demonstrated that Pitx3 binds to an evolutionary
      conserved bicoid-binding site on the 5'-upstream region of Foxe3. Finally, Pitx3
      binding to 5'-upstream region of Foxe3 increased transcriptional activity
      significantly in a cell-based reporter assay. Identification of Foxe3 as a
      transcriptional target of Pitx3 explains at least in part some of the phenotypic
      similarities of the ak and dyl mice (dysgenic lens, a Foxe3 allele). These
      findings enhance our understanding of the molecular cascades which subserve lens
      development.

PMID- 24307299
TI  - Unraveling new roles for serotonin receptor 2B in development: key findings from
      Xenopus.
AB  - The serotonin receptor 5-HT2B has been shown to be critically important during
      embryogenesis as the knockout of this gene in mice causes heart defects and
      embryonic lethality that impairs further analyses on other embryonic cell and
      tissue types. In the present review, we highlight how the use of Xenopus laevis,
      an alternative vertebrate model suitable for gene loss and gain of function
      analyses, has contributed to our understanding of the role of 5-HT2B signaling
      during development. In vivo studies showed that 5-HT2B signaling is not only
      required for heart development, but that it also has a crucial role in ocular and
      craniofacial morphogenesis, being involved in shaping the first branchial arch
      and the jaw joint, in retinogenesis and possibly in periocular mesenchyme
      development. These findings may be relevant for our understanding of congenital
      defects including human birth malformations. In addition, 5-HT2B appears to be
      required for the therapeutic actions of selective serotonin reuptake inhibitors
      commonly prescribed as antidepressant drugs to pregnant and lactating women. We
      discuss how the understanding of the molecular basis of serotonin signaling in a
      suitable animal embryogenesis model may open new lines of investigations and
      therapies in humans. 

PMID- 24307300
TI  - Identification of promoter elements responsible for gonad-specific expression of
      zebrafish Deadend and its application to ovarian germ cell derivation.
AB  - We discovered that a 150-bp region of zebrafish deadend (dnd) spanning the
      translation start codon, exon 1 and part of intron 1 is required to direct
      heterologous neomycin-resistance gene (neo) expression specifically in the gonad,
      similar to endogenous dnd. Using an 8.3-kb dnd promoter that contains this 150-bp
      region, we generated Tg(dnd:neo-dnd) transgenic zebrafish in which the expression
      of Neo was detected specifically in ovarian germ cells. The transgenic fish were
      used to initiate primary ovarian germ cell cultures with antibiotic G418 to
      select ovarian germ cells and eliminate ovarian somatic cells. RT-PCR results
      demonstrated that the drug-selected ovarian germ cells continued to express germ
      cell markers nanos3, vasa and dnd. Growth assays demonstrated that recombinant
      zebrafish Lif had a significant mitogenic effect on the ovarian germ cells. When
      long-term ovarian germ cell cultures were transplanted into two-week-old
      infertile larvae, they successfully colonized and directed the formation of a
      truncated gonad in the recipient adult fish. Histological examination of the
      recipient adult fish revealed that 9 out of 34 individuals (26%) possessed donor
      derived cells in their gonads. The identification of zebrafish dnd promoter and
      the use of this promoter to generate Tg(dnd:neo-dnd) led to the success of germ
      cell isolation through drug selection to generate homogenous germ cells that can
      be used to study zebrafish germ cell biology and may lead to a cell-mediated gene
      transfer strategy. 

PMID- 24307301
TI  - Signaling pathways dictating pluripotency in embryonic stem cells.
AB  - Embryonic Stem Cells (ESCs) are derived from the inner cell mass of blastocysts.
      They have the unique potency to differentiate into diverse lineages. Hence, they
      are bestowed with the term pluripotency. Several mechanisms have been implicated
      in maintaining the pluripotency of ESCs. This review will focus on the role of
      signaling pathways in regulating ESC pluripotency among diverse mammalian
      species. A novel phylogenetic approach has been designed to understand the
      structural basis of divergence in the signaling pathways which modulate
      pluripotency among different species. Detailed insight into different signaling
      mechanisms indicates inhibition of Extracellular Related Kinase 1/2 (ERK 1/2)
      signaling as the key component regulating the pluripotency of ESCs. On the basis
      of recent advances made in this field, it can be hypothesized that expression of
      the transcription factor KLF4 and inhibition of ERK signaling may promote the
      establishment and maintenance of true ESCs from different mammalian species. 

PMID- 24307302
TI  - Zfyve9a regulates the proliferation of hepatic cells during zebrafish
      embryogenesis.
AB  - Zfyve9 is a FYVE domain protein first identified as a binding partner for
      SMAD2/3. In vitro studies indicate that it can function either positively or
      negatively in the TGF-beta signaling pathway depending on the cell lines used.
      However, the in vivo function of this protein remains to be investigated. We
      first analyzed the tissue distribution of zebrafish zfyve9a by in situ
      hybridization. To investigate the in vivo function of this gene, we performed
      morpholino mediated loss-of-function assays. We analyzed the expression patterns
      of liver (cp and fabp10a), pancreas (trypsin and insulin) or gut (fabp2) specific
      markers to determine whether the formation of these organs is affected by zfyve9a
      knockdown. We determined the specification of hepatoblast in the zfyve9a
      morphants (prox1a) and investigated the proliferation and survival of hepatic
      cells in the morphants by P-H3 staining and TUNEL assay respectively. We report
      here that zfyve9a is enriched in the zebrafish embryonic liver and required for
      hepatogenesis. Morpholino mediated knockdown of zfyve9a inhibits the formation of
      liver by day 4 while the other endoderm-derived organs appear unaffected. We
      demonstrated that the specification of hepatoblasts is normal in the zfyve9a
      morphants; however, the proliferation rate of these cells is reduced. Thus, our
      results reveal the liver-specific function of zfyve9a during early embryogenesis
      and indicate that the zfyve9a mediated signal is essential for the proliferation
      of hepatic cells during the expansion of liver bud. 

PMID- 24307303
TI  - Analysis of Cripto expression during mouse cardiac myocyte differentiation.
AB  - Vertebrate cardiac progenitor cells are initially allocated in two distinct
      domains, the first and second heart fields. It has been demonstrated that first
      heart field cells give rise to the myocardial cells in the left ventricle and
      part of the atria, whereas second heart field cells move into the developing
      heart tube and contribute to the myocardium of the outflow tract and right
      ventricle and the majority of atria. In this study, we have examined the
      expression of the mouse Cripto gene and the lineage of Cripto-expressing cells,
      focusing on its relationship with cardiac myocyte differentiation. The mouse
      Cripto gene is initially expressed at late head fold (LHF) stages in the cardiac
      crescent region, known as the first heart field; later in the medial region of
      the early heart tube, and by embryonic day 8.5, it is localized to the outflow
      tract. Using a Cripto-LacZ allele, we found that Cripto- expressing progeny cells
      contribute to the myocardium of the entire outflow tract and right ventricle, as
      well as to a majority of cells within the left ventricle. In contrast, no Cripto-
      expressing progeny cells were found in the atria or atrio-ventricular canal.
      Therefore, Cripto is transiently expressed in early differentiating myocardial
      cells of the left ventricle, right ventricle and outflow tract between LHF stages
      and E8.5. Cripto expression is subsequently downregulated as cells undergo
      further differentiation. 

PMID- 24307304
TI  - Kidins220/ARMS is dynamically expressed during Xenopus laevis development.
AB  - Kidins220 (Kinase D interacting substrate of 220 kDa)/ARMS (Ankyrin Repeat-rich
      Membrane Spanning) is a conserved scaffold protein that acts as a downstream
      substrate for protein kinase D and mediates multiple receptor signalling
      pathways. Despite the dissecting of the function of this protein in mammals,
      using both in vitro and in vivo studies, a detailed characterization of its gene
      expression during early phases of embryogenesis has not been described yet. Here,
      we have used Xenopus laevis as a vertebrate model system to analyze the gene
      expression and the protein localization of Kidins220/ARMS. We found its
      expression was dynamically regulated during development. Kidins220/ARMS mRNA was
      expressed from neurula to larval stage in different embryonic regions including
      the nervous system, eye, branchial arches, heart and somites. Similar to the
      transcript, the protein was present in multiple embryonic domains including the
      central nervous system, cranial nerves, motor nerves, intersomitic junctions,
      retinal ganglion cells, lens, otic vesicle, heart and branchial arches. In
      particular, in some regions such as the retina and somites, the protein displayed
      a differential localization pattern in stage 42 embryos when compared to the
      earlier examined stages. Taken together our results suggest that this multidomain
      protein is involved in distinct spatio-temporal differentiative events. 

PMID- 24307305
TI  - Self-assembled microspheres driven by dipole-dipole interactions: UCST-type
      transition in water.
AB  - A double hydrophilic block copolymer, poly(ethylene glycol)-poly(3-dimethyl
      (methacryloyloxyethyl) ammonium propane sulfonate) (PEG-SB), is synthesized by
      reversible addition-fragmentation transfer (RAFT) polymerization using PEG methyl
      ether (4-cyano-4-pentanoate dodecyl trithiocarbonate) as a chain transfer agent.
      PEG-SB forms multi-layered microspheres with dipole-dipole interactions of the SB
      side chains as the driving force. The PEG-SB polymers show an upper critical
      solution temperature (UCST) and the UCST is controllable by the polymerization
      degree. The PEG-SB microspheres are dissociated above the UCST and then
      monodispersed microspheres (~1 MUm) are obtained when the solution temperature is
      decreased below the UCST again. The disassociation/association of the
      microspheres is also controllable using the concentration of NaCl. These multi
      responsive microspheres could be a powerful tool in the field of nano
      biotechnology. 

PMID- 24307306
TI  - Segregation indices for disease clustering.
AB  - Spatial clustering has important implications in various fields. In particular,
      disease clustering is of major public concern in epidemiology. In this article,
      we propose the use of two distance-based segregation indices to test the
      significance of disease clustering among subjects whose locations are from a
      homogeneous or an inhomogeneous population. We derive the asymptotic
      distributions of the segregation indices and compare them with other distance
      based disease clustering tests in terms of empirical size and power by extensive
      Monte Carlo simulations. The null pattern we consider is the random labeling (RL)
      of cases and controls to the given locations. Along this line, we investigate the
      sensitivity of the size of these tests to the underlying background pattern
      (e.g., clustered or homogenous) on which the RL is applied, the level of
      clustering and number of clusters, or to differences in relative abundances of
      the classes. We demonstrate that differences in relative abundances have the
      highest influence on the empirical sizes of the tests. We also propose various
      non-RL patterns as alternatives to the RL pattern and assess the empirical power
      performances of the tests under these alternatives. We observe that the empirical
      size of one of the indices is more robust to the differences in relative
      abundances, and this index performs comparable with the best performers in
      literature in terms of power. We illustrate the methods on two real-life examples
      from epidemiology.

PMID- 24307307
TI  - Formation of heat-induced cottonseed congossypin(7S) fibrils at pH 2.0.
AB  - BACKGROUND: Heat-induced protein aggregation is important for the texture of
      various food products. Many types of food proteins have been found to assemble
      into fibrillar structures under certain conditions. We studied fibril formation
      of cottonseed 7S storage protein upon heating (for 0-720 min) at 90 degrees C and
      pH 2.0, investigated the conversion rate, and determined the extent of thermal
      aggregation. RESULTS: Thioflavin-T fluorescence and Congo-red analysis indicated
      the formation of amyloid-like fibrils upon heating. Centrifugal filtration
      indicated that the conversion was very low (<10%) until congossypin concentration
      up to 2 mg mL(-1), and the conversion increases with increasing heating time, but
      levels off after longer heating times. Dynamic light scattering and atomic force
      microscopy showed that the extent of thermal aggregation at pH 2.0, or contour
      length of the worm-like and fine-stranded aggregates, progressively increased
      with increasing heating time. Furthermore, reducing electrophoresis analyses
      indicated that progressive polypeptide hydrolysis occurred upon heating.
      Experiments indicate that congossypin can form heat-induced amyloid-like
      aggregates and the conversion of congossypin monomers into fibrils increased with
      heating time and protein concentration. CONCLUSION: The results would be of vital
      importance for the utilisation of cottonseed proteins to produce thermally
      induced fibrillar gels with excellent properties.

PMID- 24307308
TI  - Progress of research on specificity of meridian acupoint efficacy.
AB  - Acupuncture point specificity is the theoretical basis for meridian and
      acupuncture theory. Also it is the key factor for the efficacy of acupuncture
      treatment. Studies on acupoint specifificity have aroused wide interest in
      scholars both at home and abroad. Some researchers abroad do not support acupoint
      specifificity. Chinese scholars have, after years of research, preliminarily
      confifirmed the existence of acupoint specifificity. However, there is still no
      conclusive evidence to support acupoint specificity in terms of its specific
      physiological foundation, underlying mechanism and laws. This paper summarizes
      and analyzes basic and clinical researches on acupoint specificity in biological
      structure, physiology and acupoint effect, provides clues for further studies and
      develops the theoretical basis for acupont specifificity. 

PMID- 24307309
TI  - Disease location identification as a major guide to acupoint selection.
AB  - Selecting acupoints according to channel pathway is the major point selection
      principle in acupuncture treatment for which there is a consensus. However,
      defining the disease location remains the premise of acupoint selection based on
      channel pathway. What is the substance of disease location identification in
      clinical acupuncture? Besides indicating acupoint selection according to channel
      pathway, what guidance can it provide for acupuncture treatment? This is the main
      topic discussed in this article. 

PMID- 24307310
TI  - Bone marrow angiogenesis in patients presenting with differential Chinese
      medicine syndrome: correlation with the clinico-pathological features of aplastic
      anemia.
AB  - OBJECTIVE: To explore differences in bone marrow angiogenesis seen in aplastic
      anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome,
      and to correlate these differences with clinical pathology. METHODS: Thirty-five
      patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with
      "yin deficiency syndrome." Bone marrow biopsies and serum were collected.
      Microvessel density (MVD) and positive expression of vascular endothelial-derived
      growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible
      factor -1alpha (HIF-1alpha), and VEGF expression were assayed by enzyme-linked
      immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by
      enzyme method and liquid chip technology was used to detected the expression of
      interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-gamma and tumor necrosis
      factor (TNF)-alpha. RESULTS: Counts for leukocytes, absolute neutrophils and
      platelets in "yin deficiency syndrome" were lower than those found in "yang
      deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of
      CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency
      syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF
      and LDH expression, and enhanced expression of HIF-1alpha as compared to "yang
      deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA
      (P<0.01), but IL-10 was decreased (P<0.05). High TNF-alpha expression was seen in
      "yang deficiency syndrome" and IFN-gamma expression was decreased in "yin
      deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively).
      CONCLUSION: AA patients have lower MVD than normals, especially in "yin
      deficiency syndrome." MVD might differentially correlate to disease severity, and
      could be dependent on bone marrow or serum VEGF expression and LDH. Additionally,
      IL-2, IL-10, IL-4 and IFN-gamma were negatively associated while IL-6 and TNF
      alpha were positively associated with MVD.

PMID- 24307311
TI  - The effect of Chaiqin Chengqi Decoction () on modulating serum matrix
      metalloproteinase 9 in patients with severe acute pancreatitis.
AB  - OBJECTIVE: To investigate the effect of Chaiqin Chengqi Decoction (, CQCQD) on
      regulating serum matrix metalloproteinase 9 (MMP-9) in patients with severe acute
      pancreatitis (SAP). METHODS: Thirty-five SAP patients hospitalized in West China
      Hospital from September 1, 2008 to February 28, 2009 were randomly assigned to
      two groups using a computer-derived random number sequence in a ratio of 1:1,
      treatment group (18 patients) and the placebo control group (17 patients). The
      patients in the treatment group were administered with CQCQD by gastric perfusion
      (50 mL/2 h) and retention enema (200 mL/6 h) for 7 days. The two groups had
      similar baseline information. The clinical indicators, including the initial
      Balthazar's computed tomography (CT) score, acute physiology and chronic health
      evaluation II (APACHE II) scores on 1st, 3rd, 5th and 7th day, incidences and
      durations of complications and the serum C-reactive protein (CRP), levels of MMP
      9 on the 1st, 3rd, 5th and 7th day, were recorded and compared between the two
      groups. RESULTS: The serum MMP-9, CRP and the APACHE II scores on the 3rd, 5th
      and 7th day in the treatment group were lower than those in the control group
      (P<0.05). The serum MMP-9 was positively correlated with the APACHE II score on
      the 1st day (r=0.430, P=0.01). The durations of acute respiratory distress
      syndrome (5.4+/-2.4 vs. 2.9+/-1.3), acute hepatitis (4.6+/-0.8 vs. 1.9+/-0.6) and
      acute heart failure (3.9+/-1.6 vs. 1.3+/-0.6, <0.05) in the control group were
      longer than those in the treatment group. CONCLUSION: CQCQD could decrease the
      serum MMP-9 to relieve the severity of clinical symptoms and prevent the
      development of multiple organ dysfunction syndrome in patients with SAP.

PMID- 24307312
TI  - Inhibition of the tubular epithelial-to-mesenchymal transition in vivo and in
      vitro by the Uremic Clearance Granule ().
AB  - OBJECTIVE: To investigate the effect of the Uremic Clearance Granule (UCG, ), a
      Chinese patent medicine, on tubular epithelial-to-mesenchymal transition (EMT) in
      a unilateral ureteral obstruction (UUO) model in vivo and transforming growth
      factor (TGF)-beta1 induced EMT of HK-2 cells in vitro. METHODS: In vivo study, 50
      Sprague Dawley rats were divided into three groups: a sham operation group
      (n=10), a UUO group (n=20), and a UUO with UCG treatment group (n=20). The UCG
      was given at a dose of 4.5 g/kg body weight per day by gavage after surgery. In
      vitro study, HK-2 cells were cultured in 10% fetal bovine serum (FBS), 10%
      healthy rat serum, 10% FBS and TGF-beta1 (10 ng/mL), 10% healthy rat serum and
      TGF-beta1, or 10% rat serum containing the uremic clearance granule and TGF
      beta1. The expression of the epithelial marker E-cadherin and the mesenchymal
      markers vimentin and alpha-smooth muscle actin (alpha-SMA) in kidney tissues and
      HK-2 cells were investigated by Western blot analysis and immunofluorescence
      staining. RESULTS: The rats of the UUO group showed obvious tubulointerstitial
      fibrosis, compared with the sham operation group rats. Tubulointerstitial
      fibrosis score was reduced by 17.5%+/-1.1% at day 7 and by 20.0%+/-1.2% at day 14
      in the UCG-treated group, compared with the UUO group. The UCG could maintained
      expression of E-cadherin and suppressed expression of vimentin and alpha-SMA in
      kidney tissues of UUO rats at days 7 and 14, as determined by Western blot
      analysis and immunofluorescence staining. Rat serum containing the UCG partially
      inhibited TGF-beta1-induced fibroblast phenotype of HK-2 cells and maintained the
      epithelial morphology of HK-2 cells in vitro. This occurred partially through a
      reduction of vimentin expression and an increase of E-cadherin expression.
      CONCLUSION: These results suggest that the UCG prevents tubular EMT and may be a
      promising agent for treating tubulointerstitial fibrosis.

PMID- 24307313
TI  - Qufeng Tongluo Prescription () inhibits mesangial cell proliferation and promotes
      apoptosis through regulating cell cycle progression.
AB  - OBJECTIVE: To study the effects and possible underlying mechanism of Qufeng
      Tongluo Prescription (, QFTL) on the regulation of mesangial cells (MCs)
      proliferation and apoptosis. METHODS: The MCs used in this experiment have
      undergone five passages induced by lipopolysaccharide (LPS). Changes in the
      proliferation, apoptosis, cell cycle regulatory proteins and mRNA expression
      levels of the MCs after administration of Benazepril or QFTL were measured by
      methyl thiazolyl tetrazolium (MTT) reduction assay, flow cytometry, Western blot
      and quantitative real-time polymerase chain reaction (qRT-PCR), respectively.
      RESULTS: The addition of Benazepril or QFTL serum inhibited LPS-induced MC
      proliferation after treatment for 24, 48 and 72 h, respectively (P<0.05 or
      P<0.01). Moreover, the inhibitory effect is more significant in the QFTL group at
      48 h (P<0.05). Compared with the control group, LPS-induced cell proliferation
      decreased the number of cells in G1 phase versus cells in S and G2/M phases,
      while the addition of QFTL and Benazepril serum increased the ratio of cells at
      G1 phase (P<0.05 or P<0.01) to cells at S phase (P<0.01), implicating the cell
      cycle inhibition effect exerted by QFTL. LPS decreased the level of MC apoptosis,
      compared with the control group (P<0.05), while QFTL and Benazepril serum
      increased the level of MC apoptosis (P<0.01). Moreover, the difference between
      the QFTL group and the Benazepril group was statistically significant (P<0.01).
      Compared with the control group, the protein and mRNA expression levels of
      cylinD1, cyclin dependent kinase 2 (CDK2) and p21 were significantly increased
      (P<0.05 or P<0.01), p27 was decreased but with no statistical significance
      (P>0.05); After being treated with QFTL and Benazepril serum, the protein and
      mRNA expression levels of cylinD1, CDK2, p21 were decreased and p27 increased
      significantly (P<0.05 or P<0.01); Compared with the Benazepril group, QFTL show
      better effects on protein and mRNA expression levels of cylinD1, CDK2 (P<0.05 or
      P<0.01) and p21 protein expression (P<0.05). CONCLUSION: QFTL inhibits MCs
      proliferation, promotes MCs apoptosis through an underlying mechanism of down
      regulating the protein and mRNA expression levels of cylinD1, CDK2, p21 and up
      regulation of the expression level of p27.

PMID- 24307314
TI  - Modified Xiaochaihu Decoction () prevents the progression of chronic pancreatitis
      in rats possibly by inhibiting transforming growth factor-beta1/Sma- and mad
      related proteins signaling pathway.
AB  - OBJECTIVE: To investigate the effect of modified Xiaochaihu Decoction (, MXD) on
      transforming growth factor-beta1/Sma- and Mad-related proteins (TGF-beta1/Smads)
      signaling pathway in rats with chronic pancreatitis (CP) induced by dibutyltin
      dichloride. METHODS: Thirty healthy male Wistar rats were randomly divided into
      the normal control group, CP group and CP+MXD-treated group. CP was induced by
      injection of dibutyltin dichloride (DBTC, 7 mg/kg of body weight) into the right
      caudal vein, and the control rats were treated with vehicle. MXD was given daily
      by gavage at a dose of 10 g/kg of body weight, starting from the day after CP
      induction. After 28-day treatment, the n-benzoyl-tyrosyl para-aminobenzoic acid
      (NBT-PABA) test was carried out to evaluate exocrine pancreatic function. Then,
      rats were sacrificed, and pancreatic tissues were harvested for histological
      evaluation. In addition, the mRNA expression of TGF-beta1, TGF-beta1 type II
      receptor (TGFbetaRII), Smad3 and Smad7 was determined in pancreatic tissues by
      using real-time polymerase chain reaction. RESULTS: Treatment of CP with MXD
      improved the PABA recovery, decreased the histological lesion, and reduced the
      mRNA expression of TGF-beta1, TGFbetaRII and Smad3 (P<0.05). However, MXD had no
      effect on Smad7 mRNA level. CONCLUSIONS: MXD could protect the pancreas against
      chronic injury and improve pancreatic exocrine function in DBTC induced rat CP
      model. Its mechanism may involve inhibition of the TGF-beta1/Smads signaling
      pathway.

PMID- 24307315
TI  - Neuroprotective effect of Chunghyuldan (Qing Xue Dan) on hypoxia-reoxygenation
      induced damage of neuroblastoma 2a cell lines.
AB  - OBJECTIVES: Chunghyuldan (CHD), a combinatorial drug that has anti-hyperlipidemic
      and antiinflammatory activities, has been shown to reduce infarct volume in a
      focal ischemia-reperfusion rat model. To explore the molecular basis of CHD's
      neuroprotective effect, we examined whether CHD shows a cell-protective activity
      and has a regulatory effect on Bax and/or B-cell leukemia/lymphoma 2 (Bcl-2)
      expression in mouse neuroblastoma 2a (N2a) cells subjected to hypoxia
      reoxygenation (H/R). METHODS: In order to evaluate the effects of CHD on the
      cytotoxicity induced from hypoxia or H/R condition, lactate dehydrogenase (LDH)
      assay was performed. To explore whether the suppression of neural damage when pre
      treated with CHD is associated with its anti-apoptotic effect, the CHD effect on
      the expression of Bcl-2 and Bax was analyzed by Western blotting analysis.
      RESULTS: Cytotoxicity of N2a cell line was slightly increased in 42 h hypoxia
      condition and dramatically increased under the H/R condition. CHD treatment
      markedly decreased the cytotoxicity in both conditions (P<0.01, P<0.05). H/R
      markedly increased the expression of the pro-apoptotic protein, Bax, but slightly
      increased the expression of the anti-apoptotic protein, Bcl-2, compared with the
      normoxia or hypoxia group. CHD significantly decreased Bax expression (P<0.01)
      and slightly decreased Bcl-2 expression (P>0.05), resulted in a reduction of
      Bax/Bcl-2 ratio in N2a cells subjected to H/R. CONCLUSION: CHD has
      neuroprotective effect in N2a cells subjected to H/R, which might be derived at
      least in part from its ability to decrease the expression of the pro-apoptotic
      protein, Bax.

PMID- 24307316
TI  - Response of osteoblast-like MC3T3-E1 cells on bioactive titanium fabricated by a
      chemical treatment process using a calcium-phosphate slurry.
AB  - We recently developed a chemical treatment process using a calcium-phosphate
      slurry for fabricating new layers consisting of hydroxyapatite and titanium
      dioxide (TiO2) on titanium (Ti) substrate. In this study, the response of
      osteoblast-like MC3T3-E1 cells on Ti substrate treated with a calcium-phosphate
      slurry was investigated to elucidate its behavior in a biological environment.
      The cellular adhesiveness and proliferation capacity did not differ significantly
      between the treated and untreated Ti substrates, suggesting that the slurry
      treatment did not cause cytotoxicity. The slurry treatment did not affect the
      increase in alkaline phosphatase activity after the induction of cell
      differentiation, whereas it was found to be significantly advantageous for the
      calcification behavior on the slurry-treated Ti substrate. In consequence, the
      hard-tissue compatibility of Ti is expected to be improved by the chemical
      treatment process using a calcium-phosphate slurry.

PMID- 24307317
TI  - Bandgap tunability in Zn(Sn,Ge)N(2) semiconductor alloys.
AB  - ZnSn1-x Gex N2 direct bandgap semiconductor alloys, with a crystal structure and
      electronic structure similar to InGaN, are earth-abundant alternatives for
      efficient, high-quality optoelectronic devices and solar-energy conversion. The
      bandgap is tunable almost monotonically from 2 eV (ZnSnN2 ) to 3.1 eV (ZnGeN2 )
      by control of the Sn/Ge ratio. 

PMID- 24307318
TI  - Lower extremity soft tissue defect reconstruction with the serratus anterior
      flap.
AB  - Reconstruction of limb-threatening lower extremity defects presents unique
      challenges. The selected method must provide adequate coverage of exposed bone,
      joints, and tendons while maximizing function of the limb. The traditional
      workhorse flaps, the free latissimus dorsi and rectus abdominis flaps, have been
      associated with donor site morbidity and bulkiness that can impair
      rehabilitation. We report a case series (n = 18) in which the free serratus
      anterior muscle flap and split thickness skin graft (STSG) was used for lower
      limb soft tissue coverage. Injuries were due to diabetes (9/18), trauma (7/18),
      and chronic venous stasis (2/18). A 94% flap survival rate was observed and all
      but one patient was ambulatory. No donor site morbidity was reported. Our series
      demonstrates that serratus anterior is an advantageous, reliable free flap with
      minimal donor site morbidity.

PMID- 24307319
TI  - Structural analysis of a maize gene coding for glutathione-S-transferase involved
      in herbicide detoxification.
AB  - We have used the cDNA clone encoding maize glutathione-S-transferase (GST I) to
      isolate a genomic DNA clone containing the complete GST I gene. Nucleotide
      sequence analysis of the cDNA and genomic clones has yielded a complete amino
      acid sequence for maize GST I and provided the exon-intron map of its gene. The
      mRNA homologous sequences in the maize GST I gene consist of a 107 bp 5'
      untranslated region, a 642 bp coding region and ~340 bp of the 3' untranslated
      region. They are divided into three exons by two introns which interrupt the
      coding region. The 5' untranslated spacer contains an unusual sequence of
      pentamer AGAGG repeated seven times. The inbred maize line (Missouri 17) contains
      a single gene for GST I, whereas the hybrid line (3780A) contains two genes.
      Nucleotide sequence analysis of the primer extended cDNA products reveals that
      the 5' untranslated regions of the two genes in the hybrid 3780A are identical
      except for a 6 bp internal deletion (or insertion). The amino acid sequence of
      maize GST I shares no apparent sequence homology with the published sequences of
      animal GST's and represents the first published sequence of a plant GST.
      re]19850813 ac]19851126. 

PMID- 24307320
TI  - Changes in translatable poly(A) RNA from differentiated potato tissues
      transformed with shoot-inducing Ti TL-DNA of Agrobacterium tumefaciens.
AB  - Two dimensional gel electrophoresis was used to examine differences in steady
      state total poly(A) RNA from untransformed potato (Solanum tuberosum cv. Maris
      Bard) and potato transformed with shoot-inducing TL-DNA from A. tumefaciens. RNA
      was compared from phenotypically very distinct in vitro cultured shoots, more
      similar grafted plants and tubers. In each case between 200-400 translation
      products were identified representing the more abundant poly(A) mRNA's. In
      general, poly(A) RNA from the transformed tissues gave more high molecular weight
      products. This increase was most evident in poly(A) RNA from shoot cultures.
      Depending on the tissue examined, 1-5% of the translation products with a
      molecular weight <43 KD were observed to increase or decrease in abundance. The
      influence of T-DNA on cellular gene expression in the different transformed
      potato tissues is discussed in relation to previously determined changes in T-DNA
      gene expression (particularly of the T-DNA cytokinin gene) and the corresponding
      changes in endogenous hormone concentrations. It is concluded that some of the
      specific changes in low molecular weight products are either directly caused by
      the increased cytokinin levels or are indirectly involved in maintaining the
      transformed phenotype. re]19850530 rv]19851206 ac]19851210. 

PMID- 24307321
TI  - Potato spindle tuber viroid infections mediated by the Ti plasmid of
      Agrobacterium tumefaciens.
AB  - Full length copies of potato spindle tuber viroid (PSTV) were introduced into
      plant cells using an Agrobacterium tumefaciens vector. Crown galls containing the
      PSTV DNA were induced on tomato plants, and the plants analysed for systemic
      replication of the viroid. Two separately derived multimeric PSTV insertions in
      the T-DNA were infectious on every plant inoculated. However, monomeric PSTV gave
      rise to significant levels of infection only when an adjacent plant promoter
      could direct transcription of + strand PSTV RNA. Our results suggest that this
      experimental system will be useful for the analysis of viroid replication. A
      second application of the results may be the use of systemic viral infection as a
      sensitive assay for transient expression of transformed DNA. re]19850917
      rv]19851203 ac]19851210. 

PMID- 24307322
TI  - Characterization of P. sativum chloroplast psbA transcripts produced in vivo, in
      vitro and in E. coli.
AB  - We have analyzed the region of the chloroplast genome from P. sativum which
      encodes the 5'-end of psbA. S1 nuclease mapping and primer extension analysis of
      chloroplast RNA revealed psbA transcripts with 5'-termini 92, 93 and 68
      nucleotides upstream from the psbA open reading frame. The psbA transcripts with
      5'-ends 92-93 nucleotides upstream from the psbA open reading frame can be
      labeled with alpha-(32)P-GTP by guanylyltransferase. DNA sequences 10 and 35 bp
      upstream from the longest psbA transcript showed homology to -10 and -35
      consensus promoter sequences in E. coli. Truncated psbA constructs which contain
      the putative psbA promoter sequences were shown to promote transcription in E.
      coli from a site similar to that used by chloroplast RNA polymerase in vivo.
      Accurate transcription of psbA constructs was also observed in a homologous in
      vitro transcription extract from chloroplasts. Sequence analysis of the region
      upstream from the psbA transcripts revealed a putative 3'-exon of a tRNA-Lys (240
      bp upstream) and an unidentified open reading frame (URF, 485 bp upstream). The
      3'-end of the URF mRNA was located approximately 240 bp from the 5'-end of the
      longest psbA transcript indicating that the URF and tRNA-Lys sequence are
      cotranscribed. Comparison of P. sativum and N. tabacum DNA sequences at the 5'
      end of psbA revealed homology between sequences coding for psbA mRNA including 40
      bp upstream from the longest psbA transcript. A second region of homology which
      includes the tRNA-Lys sequence was also located. In contrast the intergenic DNA
      exhibited extensive divergence in size and sequence. re]19850627 rv]19851211
      ac]19851216. 

PMID- 24307323
TI  - Characterization of a chloroplast DNA sequence from Chlorella ellipsoidea that
      promotes autonomous replication in yeast.
AB  - An EcoRI 2.7 kbp fragment from Chlorella ellipsoidea chloroplast DNA (cpDNA)
      cloned in YIp5 was shown to promote autonomous replication in Saccharomyces
      cerevisiae. The fragment was localized in the small single copy region close to
      the inverted repeat. The ARS activity (autonomously replicating sequences in
      yeast) was found to be confined within a subclone of a ca. 300 bp HindIII
      fragment. Sequence analysis of this fragment revealed its high AT content and the
      presence of several direct and inverted repeats and a few elements that were
      related to the yeast ARS consensus sequence. Electron microscopic studies
      revealed that this sequence did not coincide with the primary replication origin
      of chloroplast DNA. The functioning of this sequence as a possible origin of
      plasmid replication in vivo is discussed. This is the first report on Chlorella
      cpDNA sequence. re]19850821 rv]19851211 ac]19851216. 

PMID- 24307324
TI  - Nucleotide sequences of two corn histone H3 genes. Genomic organization of the
      corn histone H3 and H4 genes.
AB  - Two histone H3 genes have been cloned from a lambdagtWESlambda.B corn genomic
      library. The nucleotide sequences show 96% homology and both encode the same
      protein, which differs from its counterpart in wheat and pea by one amino acid
      substitution. The 5'-flanking regions of the two corn H3 genes contain the
      classical histone-gene-specific consensus sequences and possess several regions
      of extensive nucleotide homology. A conserved octanucleotide 5'-CGCGGATC-3'
      occurs at approximately 200 nucleotides upstream from the initiation ATG codon.
      This octanucleotide was found to exist in all of the 7 plant histone genes
      sequenced so far. Codon usage is characterized by a very high frequency of C
      (67%) and G (28%) at the third position of the codons, those ending by A (1%) and
      T (4%) being practically excluded.Comparison of Southern blots of EcoRI, EcoRV
      and BamHI digested genomic DNA suggests that the corn H3 and H4 genes are not
      closely associated. The H3 genes exist as 60 to 80 copies and the H4 genes as 100
      to 120 copies per diploid genome. re]19851002 rv]19851212 ac]19851216. 

PMID- 24307325
TI  - Sequence organization of the chloroplast ribosomal spacer of Chlamydomonas
      reinhardii: uninterrupted tRNAile and tRNAala genes and extensive secondary
      structure.
AB  - The 1805 bp spacer between the chloroplast ribosomal 16S and 7S RNA genes of
      Chlamydomonas reinhardii has been sequenced. It contains the genes of tRNA ala
      and tRNA ile which are both uninterrupted. The spacer includes several short
      direct and inverted repeats and a large palindromic structure which maps in the
      region where DNA rearrangements have occurred in other Chlamydomonas species. 

PMID- 24307326
TI  - Identification of hairy root loci in the T-regions of Agrobacterium rhizogenes Ri
      plasmids.
AB  - Agrobacterium rhizogenes induces root formation at the wound site of inoculation
      in plants and inserts a fragment of its plasmid (Ri) into the plant nuclear DNA.
      Parts of the transferred region (T-region) of the Ri plasmid of A. rhizogenes
      strain A4 or 8196 are cloned in Escherichia coli. Insertions of the E. coli lacZ
      coding region into the hybrid plasmids were made in vivo using transduction by
      miniMu. Twenty insertions localized in the TL-DNA of pRiA4 (or pRi1855) and 2
      inserts in the T-DNA of pRi8196 were obtained in E. coli. One of the TL-DNA
      insertions is saved up because it is linked to an internal T-DNA deletion; the
      others because they confer a lactose plus phenotype on E. coli; this indicates
      that the T-DNA harbours sequences that are expressed in E. coli. Fifteen of these
      T-DNA insertions were transfered to Agrobacterium where they substitute the
      corresponding wild-type T-DNA of the Ri plasmid by homologous recombination.
      These strains corresponding to insertion-directed mutagenesis were used to
      inoculate Daucus carota slices and stems and leaves of Kalanchoe daigremontiana.
      The two insertions strains obtained in the T-DNA of pRi8196 are avirulent on K.
      daigremontiana; but their phenotypes differ on D. carota slices, suggesting that
      insertions affect distinct loci on the T-DNA involved in hairy root formation.
      Only one insertion out of the twenty obtained in the TL-DNA of pRiA4 (or 1855)
      induces a loss of virulence on leaves of K. daigremontiana. However the TL-DNA
      deletion harbouring strain induces a loss of virulence on D. carota and K.
      daigremontiana (stems and leaves), confirming the importance of the TL-DNA for
      hairy root induction. re]19850711 rv]19851230 ac]19860114. 

PMID- 24307327
TI  - Biologically active transcripts of cloned DNA of the coat protein messenger of
      two plant viruses.
AB  - To initiate infection, a mixture of the three genomic RNAs of alfalfa mosaic
      virus (AIMV) has to be supplemented with a small amount of coat protein or RNA 4,
      the subgenomic messenger for coat protein. The possibility to replace RNA 4 in
      the inoculum by in vitro synthesized transcripts of a cloned DNA copy of the coat
      protein cistron was investigated using the SP6 transcription system. Transcripts
      with or without the cap structure m(7)G(5')ppp(5')G were both translated in vitro
      in viral coat protein, but only capped transcripts yielded an infectious mixture
      when added to the AIMV genomic RNAs. This indicates that the cap structure is
      essential to the in vivo translatin of RNA 4. Similar results were obtained with
      RNAs transcribed in vitro from a DNA copy of the putative coat protein cistron of
      tobacco streak virus (TSV). re]19850822 rv]19851203 ac]19860114. 

PMID- 24307328
TI  - Unexpected room-temperature ferromagnetism in nanostructured Bi2Te3.
AB  - There is an urgent need for the development in the field of the magnetism of
      topological insulators, owing to the necessity for the realization of the quantum
      anomalous Hall effect. Herein, we discuss experimentally fabricated
      nanostructured hierarchical architectures of the topological insulator Bi2Te3
      without the introduction of any exotic magnetic dopants, in which intriguing room
      temperature ferromagnetism was identified. First-principles calculations
      demonstrated that the intrinsic point defect with respect to the antisite Te site
      is responsible for the creation of a magnetic moment. Such a mechanism, which is
      different from that of a vacancy defect, provides new insights into the origins
      of magnetism. Our findings may pave the way for developing future Bi2Te3-based
      dissipationless spintronics and fault-tolerant quantum computation.

PMID- 24307329
TI  - Antimicrobial management of septic arthritis of the hand and wrist.
AB  - PURPOSE: The optimal antimicrobial treatment for patients with hand or wrist
      septic arthritis is unknown. We report the treatment outcomes in patients with
      these infections. METHODS: The medical records of 40 consecutive adult patients
      with hand or wrist septic arthritis treated at our institution from 2000 to 2008
      were retrospectively reviewed. The primary outcome measure was treatment failure
      (histopathologic or microbiologic evidence of relapsed infection from the same
      joint or a contiguous anatomic area). RESULTS: Involved joints were the wrist (n
      = 10, 25 %), metacarpal-phalangeal (n = 11, 27.5 %), proximal interphalangeal (n
      = 8, 20 %), distal interphalangeal (n = 10, 25 %), and thumb interphalangeal (n =
      1, 2.5 %). Methicillin-sensitive (n = 15, 45 %) and -resistant (n = 7, 17.5 %)
      Staphylococcus aureus were the most common pathogens. Surgical therapies included
      open arthrotomy with debridement (n = 33, 82.5 %), arthroscopic debridement (n =
      2, 5 %), and aspiration alone (n = 5, 12.5 %). Most patients (23/40, 58 %)
      received less than 1 week of parenteral antimicrobial therapy. Only two patients
      developed definite antimicrobial treatment failure, one of whom had an atypical
      mycobacterium infection. Patients with subacute to chronic infections were at
      high risk for finger amputation. CONCLUSIONS: When combined with surgical
      debridement, relatively short courses of parenteral antimicrobial treatment (<1
      week) supplemented with oral therapy for an additional 2-3 weeks is usually
      sufficient antimicrobial therapy for hand or wrist septic arthritis.

PMID- 24307330
TI  - Multi-state models for colon cancer recurrence and death with a cured fraction.
AB  - In cancer clinical trials, patients often experience a recurrence of disease
      prior to the outcome of interest, overall survival. Additionally, for many
      cancers, there is a cured fraction of the population who will never experience a
      recurrence. There is often interest in how different covariates affect the
      probability of being cured of disease and the time to recurrence, time to death,
      and time to death after recurrence. We propose a multi-state Markov model with an
      incorporated cured fraction to jointly model recurrence and death in colon
      cancer. A Bayesian estimation strategy is used to obtain parameter estimates. The
      model can be used to assess how individual covariates affect the probability of
      being cured and each of the transition rates. Checks for the adequacy of the
      model fit and for the functional forms of covariates are explored. The methods
      are applied to data from 12 randomized trials in colon cancer, where we show
      common effects of specific covariates across the trials.

PMID- 24307331
TI  - Generation of AQP2-Cre transgenic mini-pigs specifically expressing Cre
      recombinase in kidney collecting duct cells.
AB  - The important differences in physiological parameters and anatomical
      characteristics of the kidney between humans and mice make it difficult to
      replicate the precise progression of human renal cystic diseases in gene
      modification mouse models. In contrast to mice, pigs are a better animal model of
      human diseases, as they are more similar in terms of organ size, structure, and
      physiological parameters. Here, we report the generation and initial examination
      of an AQP2-Cre transgenic (Tg) Chinese miniature (mini)-pig line that expresses
      Cre recombinase exclusively in kidney collecting duct cells. An 8-kb fragment of
      the mini-pig aquaporin 2 (AQP2) 5'-flanking region was utilized to direct Cre
      expression in Tg mini-pigs. Two Tg mini-pigs were generated by pig somatic cell
      nuclear transfer and both carried the entire coding sequence of Cre recombinase.
      RT-PCR and western blotting analysis revealed that Cre recombinase was uniquely
      expressed in the kidney, while immunohistochemical studies located its expression
      in kidney collecting duct cells. Furthermore, six integration sites and 12-14
      copies of the Cre gene were detected in various tissues by high-efficiency
      thermal asymmetric interlaced PCR and absolute quantitative real-time PCR,
      respectively. Combined with previous studies of Cre recombinase activity, we
      believe that this AQP2-Cre Tg mini-pig line will be a useful tool to generate
      kidney collecting duct cell-specific gene knockout mini-pig models, thereby
      allowing the investigation of gene functions in kidney development and the
      mechanisms of human renal cystic disease. 

PMID- 24307332
TI  - Dual-treatment autodissemination station with enhanced transfer of an insect
      growth regulator to mosquito oviposition sites.
AB  - BACKGROUND: The Asian tiger mosquito, Aedes albopictus (Skuse), transmits
      important arboviral diseases and displaces native species. This peridomestic
      mosquito deposits eggs in natural and artificial containers. Container larval
      habitats tend to be cryptic and, therefore, difficult to reach by conventional
      insecticide treatments. We have developed an autodissemination station that
      transfers the insect growth regulator, pyriproxyfen, from the station to
      oviposition sites. Mosquitoes visiting the station become contaminated with an
      oil sticker followed by pyriproxyfen powder before exiting. RESULTS: In a room
      (31 m(3) ) bioassay a single station consistently achieved 100% Ae. albopictus
      pupal mortality against 10 oviposition containers. In a greenhouse (200 m(3) )
      assay with two stations and 12 oviposition cups, 91.7% of the cups had been
      contaminated as shown, and 57.1% pupal mortality was recorded. Pyriproxyfen
      transfer was also detected by visualizing mosquito 'tarsal prints' using a
      fluorescent dye. CONCLUSIONS: The oil and pyriproxyfen powder dual-treatment
      station enhanced autodissemination efficacy by increasing toxicant attachment and
      retention on contaminated females. The autodissemination station offers a
      targeted, less environmentally damaging approach to manage cryptic container
      species.

PMID- 24307333
TI  - The photoredox-catalyzed Meerwein addition reaction: intermolecular amino
      arylation of alkenes.
AB  - A variety of amides are efficiently accessible under mild conditions by
      intermolecular amino-arylation using a photo Meerwein addition with visible
      light. The reaction has a broad substrate scope, tolerates a large range of
      functional groups, and was applied to the synthesis of a 3-aryl-3,4
      dihydroisoquinoline. 

PMID- 24307334
TI  - [The specific role of medical psychotherapy as seen by somatic physicians in
      general hospitals].
AB  - OBJECTIVES: We examined the attitude towards the importance of medical
      psychotherapy among physicians working in a hospital. We focused on their opinion
      about the general role of medical psychotherapy within the health care system as
      well as on their opinion about the importance of medical psychotherapy in
      different clinical situations. METHOD: 105 physicians with various clinical
      specialties were interviewed using a questionnaire designed for this purpose.
      RESULTS: From the point of view of the interviewed physicians, medical
      psychotherapy plays an important role. Especially medical psychotherapists are
      considered to be competent in cases of life-threatening situations resulting from
      mental disorders (such as suicide, anorexia nervosa), in psychopharmacological
      treatment as well as in cases of medically unexplained physical symptoms.
      Furthermore, medical competence in psychotherapy is requested wherever there is
      close connection to physical illness (such as stressful events in medical
      contexts). CONCLUSIONS: Especially in times of increasing specialization of
      physicians there is a need for medical psychotherapy in inpatient health care and
      clinical consultation.

PMID- 24307335
TI  - [Patterns of dysfunctional parenting styles and psychological disturbances in
      offspring].
AB  - OBJECTIVES: Dysfunctional parenting styles represent a risk factor for the
      development of psychological disturbances. The present study investigated the
      differential validity of the German language Fragebogen zur Erfassung
      dysfunktionaler Erziehungsstile (FDEB; Measurement of Parental Styles, MOPS) and
      determined whether different forms of psychological disorders are associated with
      specific patterns of parenting styles. METHODS: 145 inpatients, 108 outpatients
      and a control group of 633 representative individuals from the general population
      were investigated by adapting the FDEB. RESULTS: A comparison of dysfunctional
      parenting styles showed different distress levels within the diagnostic groups:
      Patients suffering from depression reported high levels of maternal indifference
      and over protectiveness together with an abusive rearing behavior on the part of
      both parents. Patients with anxiety disorders reported having overprotective
      mothers. Bulimic patients as well as those with personality disorders
      significantly exhibited stress in almost all areas. However, anorexic patients
      did not differ significantly from the control group, which appeared to be the
      least affected of all. CONCLUSION: The FDEB showed a satisfactory differential
      validity. There was evidence that specific patterns of dysfunctional parenting
      styles were associated with different diagnostic groups.

PMID- 24307336
TI  - [Utilization and utility of psycho-oncologic support of patients with mamma
      carcinoma].
AB  - OBJECTIVES: This study explores patients' utilization of psycho-oncologic support
      and the effectiveness thereof. METHODS: At the hospital in Munich-Harlaching, 51
      patients were recruited following their first admission to the breast centre, 27
      of whom utilized the psycho-oncologic service. They were compared to 24 decliners
      of the service. All patients completed self-rating questionnaires (Distress
      Thermometer and Patient Health Questionnaire) at admission and at release. Group
      differences were calculated statistically by chi-square- and t-tests. RESULTS: We
      found no significant differences between users and decliners concerning socio
      demographic and somatic data, but there were significant group differences in
      mental health. Users reported more mental distress and more depressive and
      anxiety symptoms. Psycho-oncologic interventions showed small to large effect
      sizes. CONCLUSIONS: Although this study corresponded more to external than to
      internal validity standards, it did yield provisional empirical evidence that
      psycho-oncologic interventions are effective in the treatment of the mental
      symptoms of breast cancer patients.

PMID- 24307337
TI  - [Basic thoughts on psychopharmacological interventions through psychotherapy of
      severe forms of post-traumatic stress disorder: a case study].
AB  - The present paper focuses on clinical issues concerning the psychopharmacological
      treatment of severe forms of post-traumatic stress disorder (PTSD).Using a case
      study, we discuss problems in this field against the background of psychodynamic
      and psychotraumatological theories. We also present strategies for the
      appropriate use of psychotropic drugs in the psychotherapy of PTSD. 

PMID- 24307338
TI  - The first step is the hardest - emotion recognition in patients with somatoform
      disorders.
AB  - OBJECTIVES: The aetiology of somatoform disorders is assumed to consist of
      several factors, as alexithymia, dysfunctional cognitions and emotion regulation.
      As a consequence of somatoform disorders social withdrawal is discussed. Several
      studies prove connections between mental problems, emotion recognition, and
      functioning social relationships. METHODS: A sample of 35 patients suffering from
      a somatoform disorder and a sample of 73 persons without any somatoform symptoms
      were investigated according to their ability to identify emotional facial
      expressions (computer-assisted presentation of photos). RESULTS: Our results
      demonstrate significant differences in the ability to decode others' emotional
      states between people with or without somatoform disorders. In all six tests the
      patients achieved significantly worse results. CONCLUSIONS: Our results suggest
      that psychotherapeutic treatment of patients with somatoform disorders should
      also focus on the recognition of emotions and deal with them.

PMID- 24307339
TI  - [Protective factors for postpartum depression].
AB  - OBJECTIVES: This article examines the associations between protective factors und
      the occurrence of postpartum depressive symptoms. METHODS: Using a prospective
      longitudinal design 303 pregnant women were examined at 3 points in time (T1: 1st
      trimester, T2: 3rd trimester, T3: 3-5 months postpartum). The analyses are based
      on T1 and T3. RESULTS: Sense of coherence (SOC-L9, Schumacher et al. 2000) at 1st
      trimester was on average 51.7 (SD = 7.2) - significantly above the mean of a
      comparison sample. 37 women (15.4 %) had a score of 10 or more on the Edinburgh
      Postnatal Depression Scale (EPDS, Cox et al. 1987) 3 to 5 months postpartum.
      Pregnant women who stated that their pregnancy had been planned and desired, with
      a higher marital and overall life satisfaction as well as a higher sense of
      coherence, had a significantly lower risk for the development of postpartum
      depression. Using multiple regression it was found that only sense of coherence
      significantly predicted postpartum depression. CONCLUSIONS: The results suggest
      that a higher sense of coherence at first trimester is an important protective
      factor for the occurrence of postpartum depression.

PMID- 24307340
TI  - [Is there adequate care for patients with psychosomatic disorders in Austria?
      Analysis of the need and a proposal for a model of quality assurance in Austrian
      psychosomatic medicine].
AB  - INTRODUCTION: Quality assurance in psychosomatic medicine in Austria is currently
      based on a voluntary continuing medical education programme in psychosocial,
      psychosomatic and psychotherapeutic medicine. It is questionable whether
      psychosomatic care can be sufficiently provided in this manner. In addition, a
      broadly based proposal to create a subspecialty in psychosomatic medicine in
      order to facilitate quality assurance, is investigated. METHODS: The necessity to
      reorganize psychosomatic care was explored through semi-structured qualitative
      interviews with experts. Data-based analyses probed the labour market of the
      proposed subspecialty, and the literature was reviewed to look into the cost
      benefit ratio of psychosomatic treatment. RESULTS: All experts expressed a need
      to restructure psychosomatic care in Austria. Examples exist for psychosomatic
      treatment with an efficient cost-benefit relation in diverse medical settings.
      CONCLUSION: Establishing a subspecialty in Psychosomatic Medicine seems feasible
      and could contribute to increased quality assurance and the nationwide provision
      of psychosomatic care.

PMID- 24307341
TI  - Comparison of soil and foliar zinc application for enhancing grain zinc content
      of wheat when grown on potentially zinc-deficient calcareous soils.
AB  - BACKGROUND: The concentration of Zn and phytic acid in wheat grain has important
      implications for human health. We conducted field and greenhouse experiments to
      compare the efficacy of soil and foliar Zn fertilisation in improving grain Zn
      concentration and bioavailability in wheat (Triticum aestivum L.) grain grown on
      potentially Zn-deficient calcareous soil. RESULTS: Results from the 2-year field
      experiment indicated that soil Zn application increased soil DTPA-Zn by an
      average of 174%, but had no significant effect on grain Zn concentration. In
      contrast, foliar Zn application increased grain Zn concentration by an average of
      61%, and Zn bioavailability by an average of 36%. Soil DTPA-Zn concentrations
      varied depending on wheat cultivars. There were also significant differences in
      grain phytic acid concentration among the cultivars. A laboratory experiment
      indicated that Zn (from ZnSO4 ) had a low diffusion coefficient in this
      calcareous soil. CONCLUSION: Compared to soil Zn application, foliar Zn
      application is more effective in improving grain Zn content of wheat grown in
      potentially Zn-deficient calcareous soils.

PMID- 24307342
TI  - Bioethics and nonhuman animals.

PMID- 24307343
TI  - Unmixing mixed-methods research.

PMID- 24307344
TI  - Passive sampling methods for contaminated sediments: state of the science for
      organic contaminants.
AB  - This manuscript surveys the literature on passive sampler methods (PSMs) used in
      contaminated sediments to assess the chemical activity of organic contaminants.
      The chemical activity in turn dictates the reactivity and bioavailability of
      contaminants in sediment. Approaches to measure specific binding of compounds to
      sediment components, for example, amorphous carbon or specific types of reduced
      carbon, and the associated partition coefficients are difficult to determine,
      particularly for native sediment. Thus, the development of PSMs that represent
      the chemical activity of complex compound-sediment interactions, expressed as the
      freely dissolved contaminant concentration in porewater (Cfree ), offer a better
      proxy for endpoints of concern, such as reactivity, bioaccumulation, and
      toxicity. Passive sampling methods have estimated Cfree using both kinetic and
      equilibrium operating modes and used various polymers as the sorbing phase, for
      example, polydimethylsiloxane, polyethylene, and polyoxymethylene in various
      configurations, such as sheets, coated fibers, or vials containing thin films.
      These PSMs have been applied in laboratory exposures and field deployments
      covering a variety of spatial and temporal scales. A wide range of calibration
      conditions exist in the literature to estimate Cfree , but consensus values have
      not been established. The most critical criteria are the partition coefficient
      between water and the polymer phase and the equilibrium status of the sampler. In
      addition, the PSM must not appreciably deplete Cfree in the porewater. Some of
      the future challenges include establishing a standard approach for PSM
      measurements, correcting for nonequilibrium conditions, establishing guidance for
      selection and implementation of PSMs, and translating and applying data collected
      by PSMs.

PMID- 24307345
TI  - Elevated expression patterns and tight correlation of the PLCE1 and NF-kappaB
      signaling in Kazakh patients with esophageal carcinoma.
AB  - This study investigated the expression of the phospholipase C epsilon 1 (PLCE1)
      and nuclear factor-kappaB (NF-kappaB)-related proteins in Kazakh patients with
      esophageal squamous cell carcinoma (ESCC). Tissue microarrays of 90 ethnic Kazakh
      patients with ESCC and exhibiting clinical characteristics were analyzed for
      protein expression of PLCE1, IKKbeta, IKBalpha, p50, and p65 by
      immunohistochemistry. Correlations between histoscores of PLCE1 and NF-kappaB
      related proteins were determined using Spearman's rank correlation tests.
      Expression of PLCE1 and NF-kappaB-related proteins significantly increased in
      tumor tissues compared with normal esophageal tissues (P = 9.48 * 10(-7), 1.24 *
      10(-5), 0.004, 0.003, and 2.83 * 10(-5), respectively). Upregulation of PLCE1 was
      significantly correlated with advanced tumor-node-metastasis stages (P = 0.018)
      and lymph node metastasis (P = 0.003). Overexpression of IKKbeta and IKBalpha was
      associated with ESCC stages I/II (P = 3.36 * 10(-4) and 0.022, respectively).
      Increased expression of p50 was significantly higher in patients with lymph node
      metastasis than without lymph node metastasis (P = 0.048). Elevated expression of
      p65 protein was significantly correlated with poor and moderately differentiated
      ESCC and depth of tumor invasion (P = 0.026 and 0.010, respectively). Significant
      positive correlations were observed between the expression of PLCE1 and NF-kappaB
      related proteins, especially IKKbeta (r = 0.246 and P = 0.025) and p50 (r = 0.244
      and P = 0.024). These results suggest, for the first time, that upregulation of
      PLCE1 is correlated with increased expression of NF-kappaB-related proteins in
      Kazakh patients with ESCC, suggesting that interaction between PLCE1 with the NF
      kappaB signal pathway may be responsible for the carcinogenesis of ESCC, such as
      ESCC-related inflammation.

PMID- 24307346
TI  - Expression level of phosphorylated-4E-binding protein 1 in radical nephrectomy
      specimens as a prognostic predictor in patients with metastatic renal cell
      carcinoma treated with mammalian target of rapamycin inhibitors.
AB  - The objective of this study was to analyze the expression levels of multiple
      components in the mammalian target of rapamycin (mTOR) signaling pathway in
      radical nephrectomy specimens from patients with metastatic renal-cell carcinoma
      (RCC) treated with mTOR inhibitors in order to identify factors predicting
      susceptibility to these agents. This study retrospectively included a total of 48
      consecutive patients undergoing radical nephrectomy, who were diagnosed with
      metastatic RCC and subsequently treated with an mTOR inhibitor (everolimus or
      temsirolimus) as either first- or second-line systemic therapy. Expression levels
      of 5 molecular markers involved in the signaling pathway associated with mTOR,
      including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p
      4E-binding protein 1 (4E-BP1), were measured by immunohistochemical staining of
      primary RCC specimens. Of several factors examined, bone metastasis, liver
      metastasis, and the expression level of p-4E-BP1 were shown to have significant
      impacts on the response to the mTOR inhibitors. Progression-free survival (PFS)
      was significantly correlated with the expression levels of PTEN and p-4E-BP1 in
      addition to the presence of bone metastasis on univariate analysis. Of these
      significant factors, p-4E-BP1 expression and bone metastasis appeared to be
      independently associated with PFS on multivariate analysis. These findings
      suggest that it would be useful to consider the expression levels of potential
      molecular markers in the mTOR signaling pathway, particularly p-4E-BP1, as well
      as conventional clinical parameters when selecting patients with metastatic RCC
      who are likely to benefit from treatment with mTOR inhibitors.

PMID- 24307347
TI  - NSE can predict the sensitivity to definitive chemoradiotherapy of small cell
      carcinoma of esophagus.
AB  - Patients with esophageal small cell carcinoma undergoing definitive
      chemoradiotherapy (CRT) seem to have disparity in tumor response. The
      identification of CRT sensitivity-related tumor markers would be helpful for
      selecting patients most likely to benefit from CRT. The aim of this study was to
      examine the predictive value of biological markers in small cell carcinoma of the
      esophagus (SCEC) patients treated with definitive CRT. Pretreatment serum levels
      of neurone-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21
      1), and carcinoembryonic antigen (CEA) were measured by immunoradiometric assays,
      while the tumor responses were evaluated according to the World Health
      Organization response criteria. The relationships between pretreatment expression
      of NSE, CYFRA21-1, CEA, and the tumor response to CRT were analyzed. The
      effective rates (complete response + partial response) in NSE high and low groups
      were 10.80 % (9/82) and 37.98 % (31/82), respectively (P = 0.003).The results
      from statistical analysis indicated that the effectiveness of CRT was
      significantly associated with the serum levels of NSE before treatment (P =
      0.002). The overall survival (OS) of the patients with high NSE levels was worse
      than that of those with low NSE levels (P = 0.004). In multivariate analysis, low
      level of NSE was the most significant independent predictor of good OS (P =
      0.003). The result showed a promising predictive value of NSE regarding to the
      sensitivity of tumors to CRT. NSE may be a reliable surrogate marker of CRT
      efficacy in patients with SCEC.

PMID- 24307348
TI  - A prospective observational study to evaluate G-CSF usage in patients with solid
      tumors receiving myelosuppressive chemotherapy in Italian clinical oncology
      practice.
AB  - Febrile neutropenia (FN) is a severe dose-limiting side effect of
      myelosuppressive chemotherapy in patients with solid tumors. Clinical practice
      guidelines recommend primary prophylaxis with G-CSF in patients with an overall
      >= 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72
      h after chemotherapy; for daily G-CSF, administration should continue until the
      absolute neutrophil count (ANC) is 1 * 10(9)/L post-nadir and should not be
      terminated after ANC increase in the early days of administration. The aim of
      this study was to assess guideline adherence in oncology practice in Italy. In
      this multicenter, prospective, observational study, patients were enrolled at the
      first G-CSF use in any cycle and were followed for two subsequent cycles (or
      until the end of chemotherapy if less than two additional cycles). Primary
      objective was to explore G-CSF use in Italian clinical practice; therefore, data
      were collected on the G-CSF type, timing of administration, and number of doses.
      512 eligible patients were enrolled (median age, 62). The most common tumor types
      were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF
      cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was
      administered later than 72 h after chemotherapy in 42 % of cycles, and the median
      [range] number of doses was four [1, 10]. Pegfilgrastim was administered later
      than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered
      in a manner which is not supported by evidence-based guidelines. As this practice
      may lead to poor outcomes, educational initiatives are recommended.

PMID- 24307349
TI  - Discordance and clinical significance of ER, PR, and HER2 status between primary
      breast cancer and synchronous axillary lymph node metastasis.
AB  - Discordance of estrogen receptor (ER), progesterone receptor (PR), and human
      epidermal growth factor receptor 2 (HER2) status between primary breast cancer,
      metastatic lesion and synchronous axillary lymph node metastasis has been
      reported in the series studies. Systemic treatment of primary invasive breast
      cancer patients with synchronous axillary metastasis is currently based on the
      biomarker characteristics of the primary tumor; however, hormone receptors and
      HER2 status may change throughout tumor progression from the primary tumor to the
      synchronous axillary metastasis. As local metastasis, the synchronous axillary
      lymph node metastasis may represent the potentially metastatic breast cancer
      cells much better than the primary tumor. Hence, the determination of hormone
      receptors and HER2 status should be routinely performed in synchronous axillary
      nodal metastasis, together with primary tumor, to guide therapy management and
      evaluate the recurrent risk of primary invasive breast cancer patients with
      synchronous axillary nodal metastasis, which may even change the postoperative
      risk categories (St. Gallen consensus) of breast cancer in these patients. This
      article will review the studies on the discordance and clinical significance of
      ER, PR, and HER2 receptor status between primary breast cancer and synchronous
      axillary lymph node metastasis.

PMID- 24307353
TI  - X-ray structure of a porphyrin-tetramethylcucurbit[6]uril supramolecular polymer.

PMID- 24307354
TI  - Ordered mesoporous core/shell SnO2/C nanocomposite as high-capacity anode
      material for lithium-ion batteries.

PMID- 24307350
TI  - Use of 2D images of depth and integrated reflectivity to represent the severity
      of demineralization in cross-polarization optical coherence tomography.
AB  - Several studies have demonstrated the potential of cross-polarization optical
      coherence tomography (CP-OCT) to quantify the severity of early caries lesions
      (tooth decay) on tooth surfaces. The purpose of this study is to show that 2D
      images of the lesion depth and the integrated reflectivity can be used to
      accurately represent the severity of early lesions. Simulated early lesions of
      varying severity were produced on tooth samples using simulated lesion models.
      Methods were developed to convert the 3D CP-OCT images of the samples to 2D
      images of the lesion depth and lesion integrated reflectivity. Calculated lesion
      depths from OCT were compared with lesion depths measured from histological
      sections examined using polarized light microscopy. The 2D images of the lesion
      depth and integrated reflectivity are well suited for visualization of early
      demineralization.

PMID- 24307355
TI  - On-surface magnetometry: the evaluation of superexchange coupling constants in
      surface-wired single-molecule magnets.

PMID- 24307356
TI  - Meteorites as catalysts for prebiotic chemistry.

PMID- 24307357
TI  - Optimizing divalent inhibitors of Pseudomonas aeruginosa lectin LecA by using a
      rigid spacer.

PMID- 24307358
TI  - Epimerization-free C-terminal peptide activation.

PMID- 24307359
TI  - Mixed oligoureas based on constrained bicyclic and acyclic beta-amino acids
      derivatives: on the significance of the subunit configuration for folding.
AB  - The combination of a non-functionalized constrained bicyclo[2.2.2]octane motif
      along with urea linkages allowed the formation of a highly rigid 2.5(12/14)
      helical system both in solution and the solid state. In this work, we aimed at
      developing stable and functionalized systems as promising materials for
      biological applications in investigating the impact of this constrained motif and
      its configuration on homo and heterochiral mixed-oligourea helix formation. Di-,
      tetra-, hexa-, and octa-oligoureas alternating the highly constrained bicyclic
      motif of (R) or (S) configuration with acyclic (S)-beta(3)-amino acid derivatives
      were constructed. Circular dichroism (CD), NMR experiments, and the X-ray crystal
      structure of the octamer unequivocally proved that the alternating heterochiral
      R/S sequences form a stable left-handed 2.5-helix in contrast to the mixed (S/S)
      oligoureas, which did not adopt any defined secondary structure. We observed that
      the (-)-synclinal conformation around the C(alpha)-C(beta) bond of the acyclic
      residues, although sterically less favorable than the (+)-synclinal conformation,
      was imposed by the (R)-bicyclic amino carbamoyl (BAC) residue. This highlighted
      the strong ability of the BAC residue to drive helical folding in heterochiral
      compounds. The role of the stereochemistry of the BAC unit was assessed and a
      model was proposed to explain the misfolding of the S/S sequences.

PMID- 24307360
TI  - Chiral photoresponsive tetrathiazoles that provide snapshots of folding states.
AB  - Herein, we designed chiral photoresponsive tetra(2-phenylthiazole)s, which induce
      a diastereoselective 6pi-electrocyclization reaction in a helically folded
      structure to freeze the conformational interconversions. The folding conformation
      with one helical turn of tetra(2-phenylthiazole)s was supported by multiple
      intramolecular noncovalent interactions including vicinal S...N interheteroatom
      interactions and CH-pi and pi-pi stacking interactions between nonadjacent units,
      as found in X-ray crystal structures as well as quantum chemical calculations.
      The introduction of a chiral group at both ends of tetra(2-phenylthiazole)
      dictates the preferential folding into a one-handed helix conformation by the
      simultaneous operation of S...O and multiple CH-pi interactions that involve the
      chiral end groups. Since the tetra(2-phenylthiazole)s possess two equivalent
      photoreactive 6pi-electron systems and the folded conformation is suitable for
      photoinduced electrocyclization reaction, they undergo a photocyclization
      reaction in a stereoselective manner to memorize the chirality of the helix in a
      resulting diastereomeric closed form.

PMID- 24307361
TI  - Preorganized anion traps for exploiting anion-pi interactions: an experimental
      and computational study.
AB  - 1,3-Bis(pentafluorophenyl-imino)isoindoline (A(F)) and 3,6-di-tert-butyl-1,8
      bis(pentafluorophenyl)-9H-carbazole (B(F)) have been designed as preorganized
      anion receptors that exploit anion-pi interactions, and their ability to bind
      chloride and bromide in various solvents has been evaluated. Both receptors A(F)
      and B(F) are neutral but provide a central NH hydrogen bond that directs the
      halide anion into a preorganized clamp of the two electron-deficient appended
      arenes. Crystal structures of host-guest complexes of A(F) with DMSO, Cl(-), or
      Br(-) (A(F):DMSO, A(F):Cl(-), and A(2)(F):Br(-)) reveal that in all cases the
      guest is located in the cleft between the perfluorinated flaps, but NMR
      spectroscopy shows a more complex situation in solution because of E,Z/Z,Z
      isomerism of the host. In the case of the more rigid receptor B(F), Job plots
      evidence 1:1 complex formation with Cl(-) and Br(-), and association constants up
      to 960 M(-1) have been determined depending on the solvent. Crystal structures of
      B(F) and B(F):DMSO visualize the distinct preorganization of the host for anion
      pi interactions. The reference compounds 1,3-bis(2-pyrimidylimino)isoindoline
      (A(N)) and 3,6-di-tert-butyl-1,8-diphenyl-9H-carbazole (B(H)), which lack the
      perfluorinated flaps, do not show any indication of anion binding under the same
      conditions. A detailed computational analysis of the receptors A(F) and B(F) and
      their host-guest complexes with Cl(-) or Br(-) was carried out to quantify the
      interactions in play. Local correlation methods were applied, allowing for a
      decomposition of the ring-anion interactions. The latter were found to contribute
      significantly to the stabilization of these complexes (about half of the total
      energy). Compounds A(F) and B(F) represent rare examples of neutral receptors
      that are well preorganized for exploiting anion-pi interactions, and rare
      examples of receptors for which the individual contributions to the binding
      energy have been quantified.

PMID- 24307362
TI  - A unified strategy for the synthesis of mucin cores 1-4 saccharides and the
      assembled multivalent glycopeptides.
AB  - By displaying different O-glycans in a multivalent mode, mucin and mucin-like
      glycoproteins are involved in a plethora of protein binding events. The
      understanding of the roles of the glycans and the identification of potential
      glycan binding proteins are major challenges. To enable future binding studies of
      mucin glycan and glycopeptide probes, a method that gives flexible and efficient
      access to all common mucin core-glycosylated amino acids was developed. Based on
      a convergent synthesis strategy starting from a shared early stage intermediate
      by differentiation in the glycoside acceptor reactivity, a common disaccharide
      building block allows for the creation of extended glycosylated amino acids
      carrying the mucin type-2 cores 1-4 saccharides. Formation of a phenyl-sulfenyl-N
      Troc (Troc=trichloroethoxycarbonyl) byproduct during N-iodosuccinimide-promoted
      thioglycoside couplings was further characterized and a new methodology for the
      removal of the Troc group is described. The obtained glycosylated 9
      fluorenylmethoxycarbonyl (Fmoc)-protected amino acid building blocks are
      incorporated into peptides for multivalent glycan display.

PMID- 24307363
TI  - Conformational change from a twisted figure-eight to an open-extended structure
      in doubly fused 36pi core-modified octaphyrins triggered by protonation:
      implication on photodynamics and aromaticity.
AB  - Two examples of core-modified 36pi doubly fused octaphyrins that undergo a
      conformational change from a twisted figure-eight to an open-extended structure
      induced by protonation are reported. Syntheses of the two octaphyrins (in which
      Ar=mesityl or tolyl) were achieved by a simple acid-catalyzed condensation of
      dipyrrane unit containing an electron-rich, rigid dithienothiophene (DTT) core
      with pentafluorobenzaldehyde followed by oxidation with 2,3-dichloro-5,6-dicyano
      1,4-benzoquinone (DDQ). The single-crystal X-ray structure of the octaphyrin (in
      which Ar=mesityl) shows a figure-eight twisted conformation of the expanded
      porphyrin skeleton with two DTT moieties oriented in a staggered conformation
      with a pi-cloud distance of 3.7 A. Spectroscopic and quantum mechanical
      calculations reveal that both octaphyrins conform to a [4n]pi nonaromatic
      electronic structure. Protonation of the pyrrole nitrogen atoms of the
      octaphyrins results in dramatic structural change, which led to 1) a large
      redshift and sharpening of absorption bands in electronic absorption spectrum, 2)
      a large change in chemical shift of pyrrole beta-CH and -NH protons in the (1)H
      NMR spectrum, 3) a small increase in singlet lifetimes, and 4) a moderate
      increase in two-photon absorption cross-section values. Furthermore, nucleus
      independent chemical shift (NICS) values calculated at various geometrical
      positions show positive values and anisotropy-induced current density (AICD)
      plots indicate paratropic ring-currents for the diprotonated form of the
      octaphyrin (in which Ar=tolyl); the single-crystal X-ray structure of the
      diprotonated form of the octaphyrin shows an extended structure in which one of
      the pyrrole ring of each dipyrrin subunit undergoes a 180 degrees  ring-flip.
      Four trifluoroacetic acid (TFA) molecules are bound above and below the molecular
      plane defined by meso-carbon atoms and are held by N-H...O, N-H...F, and C-H...F
      intermolecular hydrogen-bonding interactions. The extended-open structure upon
      protonation allows pi-delocalization and the electronic structure conforms to a
      [4n]pi Huckel antiaromatic in the diprotonated state.

PMID- 24307364
TI  - Structure-based optimization of the terminal tripeptide in glycopeptide dendrimer
      inhibitors of Pseudomonas aeruginosa biofilms targeting LecA.
AB  - The galactopeptide dendrimer GalAG2 ((beta-Gal-OC6H4CO-Lys-Pro-Leu)4(Lys-Phe-Lys
      Ile)2Lys-His-Ile-NH2) binds strongly to the Pseudomonas aeruginosa (PA) lectin
      LecA, and it inhibits PA biofilms, as well as disperses already established ones.
      By starting with the crystal structure of the terminal tripeptide moiety GalA-KPL
      in complex with LecA, a computational mutagenesis study was carried out on the
      galactotripeptide to optimize the peptide-lectin interactions. 25 mutants were
      experimentally evaluated by a hemagglutination inhibition assay, 17 by isothermal
      titration calorimetry, and 3 by X-ray crystallography. Two of these tripeptides,
      GalA-KPY (dissociation constant (K(D))=2.7 MUM) and GalA-KRL (K(D)=2.7 MUM), are
      among the most potent monovalent LecA ligands reported to date. Dendrimers based
      on these tripeptide ligands showed improved PA biofilm inhibition and dispersal
      compared to those of GalAG2, particularly G2KPY ((beta-Gal-OC6H4CO-Lys-Pro
      Tyr)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2). The possibility to retain and even
      improve the biofilm inhibition in several analogues of GalAG2 suggests that it
      should be possible to fine-tune this dendrimer towards therapeutic use by
      adjusting the pharmacokinetic parameters in addition to the biofilm inhibition
      through amino acid substitutions.

PMID- 24307365
TI  - Role of dicarboxylate linkers in Mn(III)-salicylaldoximate based extended
      structures: synthesis, structures, and magnetic behavior.
AB  - Four new oxo-centered Mn(III)-salicylaldoximate triangle-based extended complexes
      [Mn(III)6O2(salox)6(EtOH)4(phda)]n.(saloxH2)n.(2H2O)n (1),
      [Mn(III)6O2(salox)6(MeOH)5(5-I-isoph)]n.(3MeOH)n (2),
      [Mn(III)6O2(salox)6(MeOH)4(H2O) (5-N3-isoph)]n.(4MeOH)n (3) and
      [Mn(III)3NaO(salox)3(MeOH)4(5-NO2-isoph)]n.(MeOH)n (H2O)n (4)
      [salox=salicylaldoximate, phda=1,3-phenylenediacetate, isoph=isophthalate] have
      been synthesized under similar reaction conditions. Single crystal X-ray
      structures show that in 1, only one type of Mn6 cluster is arranged in 1D,
      whereas in 2 and 3 there are two types of clusters, differing in the way the
      triangle units are joined and assembled. In complex 4, however, the basic
      building structure is heteronuclear and based on Mn3 units extended in 2D.
      Susceptibility measurements (dc and ac) over a wide range of temperatures and
      fields show that the complexes 1, 2, and 3 behave as single molecule magnets
      (SMMs) with S=4 ground state, while 4 is dominantly antiferromagnetic with a
      ground spin state S=2. Density functional theory calculations have been performed
      on model complexes to provide a qualitative theoretical interpretation for their
      overall magnetic behavior.

PMID- 24307366
TI  - Photoinduced charge separation in zinc-porphyrin/tungsten-alkylidyne dyads:
      generation of reactive porphyrin and metallo radical states.
AB  - The luminescent tungsten-alkylidyne metalloligand [WCl(=C-4,4'-C6H4CC-py)(dppe)2]
      (1; dppe=1,2-bis(diphenylphosphino)ethane) and the zinc-tetraarylporphyrins ZnTPP
      and ZnTP(Cl)P (TPP=tetraphenylporphyrin, TP(Cl)P=tetra(p-chlorophenyl)porphyrin)
      self-assemble in fluorobenzene solution to form the dyads ZnTPP(1) and
      ZnTP(Cl)P(1), in which the metalloligand is axially coordinated to the porphyrin.
      Excitation of the porphyrin-centered S1 excited states of these dyads initiates
      intramolecular energy-transfer (ZnPor->1) and electron-transfer (1->ZnPor)
      processes, which together efficiently quench the S1 state (~90%). Transient
      absorption spectroscopy and an associated kinetic analysis reveal that the net
      product of the energy-transfer process is the (3)[dpi*] state of coordinated 1,
      which is formed by S1->(1)[dpi*] singlet-singlet (Forster) energy transfer
      followed by (1)[dpi*]->(3)[dpi*] intersystem crossing. The data also demonstrate
      that coordinated 1 reductively quenches the porphyrin S1 state to produce the
      [ZnPor(-)][1(+)] charge-separated state. This is a rare example of the reductive
      quenching of zinc porphyrin chromophores. The presence in the [ZnPor(-)][1(+)]
      charge-separated states of powerfully reducing zinc-porphyrin radical anions,
      which are capable of sensitizing a wide range of reductive electrocatalysts, and
      the 1(+) ion, which can initiate the oxidation of H2, produces an integrated
      photochemical system with the thermodynamic capability of driving photoredox
      processes that result in the transfer of renewable reducing equivalents instead
      of the consumption of conventional sacrificial donors.

PMID- 24307367
TI  - An iron impurity in multiwalled carbon nanotube complexes with chitosan that
      biomimics the heme-peroxidase function.
AB  - A new biomimetic functional system having an impure multiwalled carbon nanotube
      (MWCNT-Fe)-chitosan biopolymer (H2N-CHIT) chemically modified glassy carbon
      electrode (GCE/[MWCNT-Fe:H2N-CHIT]) has been developed and demonstrated efficient
      hydrogen peroxide electrocatalytic and electrochemical sensing applications in pH
      7 phosphate buffer solution (PBS). The hybrid system showed a stable and well
      defined surface confined redox peak at an apparent electrode potential, E degrees
      '=-0.22 V versus Ag/AgCl with surface excess value 13.63 nmol cm(-2).
      Physicochemical characterizations of the hybrid by using FESEM, TEM, Raman
      spectroscopy, FTIR, and various control electrochemical experiments revealed that
      the iron impurity in the MWCNT interacted with the amino functional group of the
      chitosan polymer and thereby formed an unique complex-like structure ([MWCNT
      Fe(III/II):NH2-CHIT]), similar to heme peroxidase with a central Fe(III/II)-redox
      active site. The biomimetic system followed Michaelis-Menten-type reaction
      kinetics for the H2O2 reduction reaction with a K(M) value of 0.23 mM. At pH 7,
      amperometric i-t sensing and flow-injection analysis of H2O2 on the biomimetic
      system showed calibration plots in windows 5-500 and 50-2500 MUM, with detection
      limit values of 2.3 and 9.7 MUM, respectively. Unlike most of the previously
      reported systems that undergo serious interferences in physiological pH, the
      biomimetic system displayed a remarkable tolerance to other co-existing
      interferants (such as cysteine, ascorbic acid, uric acid, nitrate, and nitrite),
      at a H2O2 detection potential similar to the peroxidase enzyme. The ability of
      the biosensor system to perform routine analyses was demonstrated by the
      detection of H2O2 present in simulated milk and clinical and cosmetic samples
      with appreciable recovery values.

PMID- 24307368
TI  - The ambivalent chemistry of a free anionic N-heterocyclic carbene decorated with
      a malonate backbone: the plus of a negative charge.
AB  - The anionic heterocycle "[maloNHC](-)", ([1](-)), is the archetype of a growing
      family of N-heterocyclic carbenes incorporating an anionic backbone; here, a
      malonate group. A comprehensive experimental exploration of its chemistry as a
      free entity (in the form of its lithium salt [1].Li) is presented, and
      rationalized using DFT calculations at the B3LYP/6-31+G** level of theory. For
      the sake of comparison, similar computations were performed on other
      representative carbene types. Reactions of [1].Li with a broad series of
      electrophilic reagents were used to ascertain its intrinsic nature as a
      nucleophilic carbene. Unexpectedly, [1].Li was also seen to react with the
      nucleophilic tert-butylisocyanide, to give an anionic ketenimine, which could be
      subsequently derivatized, either into an imine by protonation of the ketenimine
      moiety, or into a neutral ketenimine by alkylation of the intracyclic malonate
      moiety. Further experiments on the electrophilic behavior of [1].Li revealed its
      unexpected reactivity toward p-chlorobenzaldehyde, resulting in a formal C-H
      activation and the first structurally characterized keto-tautomer of the Breslow
      intermediate. Finally, [1].Li remarkably activates polar E-H bonds, including N-H
      bonds from ammonia and amines, Si-H bonds, and B-H bonds. Importantly, DFT
      calculations indicate the importance of counterion effects. In particular, the
      key to the observed reactivity appears to be a modulation of energy levels
      associated with a dynamic variability of the Li-O distance between the remote
      malonate group and the counterion.

PMID- 24307369
TI  - La2@C(s)(17,490)-C76: a new non-IPR dimetallic metallofullerene featuring
      unexpectedly weak metal-pentalene interactions.
AB  - Although all the pure-carbon fullerene isomers above C60 reported to date comply
      with the isolated pentagon rule (IPR), non-IPR structures, which are expected to
      have different properties from those of IPR species, are obtainable either by
      exohedral modification or by endohedral atom doping. This report describes the
      isolation and characterization of a new endohedral metallofullerene (EMF),
      La2@C76, which has a non-IPR fullerene cage. The X-ray crystallographic result
      for the La2@C76/[Ni(II)(OEP)] (OEP=octaethylporphyrin) cocrystal unambiguously
      elucidated the C(s)(17,490)-C76 cage structure, which contains two adjacent
      pentagon pairs. Surprisingly, multiple metal sites were distinguished from the X
      ray data, which implies dynamic behavior for the two La(3+) cations inside the
      cage. This dynamic behavior was also corroborated by variable-temperature (139)La
      NMR spectroscopy. This phenomenon conflicts with the widely accepted idea that
      the metal cations in non-IPR EMFs invariably coordinate strongly with the
      negatively charged fused-pentagon carbons, thereby providing new insights into
      modern coordination chemistry. Furthermore, our electrochemical and computational
      studies reveal that La2@C(s)(17,490)-C76 has a larger HOMO-LUMO gap than other
      dilanthanum-EMFs with IPR cage structures, such as La2@D(3h)(5)-C78 and
      La2@I(h)(7)-C80, which implies that IPR is no longer a strict rule for EMFs.

PMID- 24307370
TI  - Bioconjugation of proteins with a paramagnetic NMR and fluorescent tag.
AB  - Site-specific labeling of proteins with lanthanide ions offers great
      opportunities for investigating the structure, function, and dynamics of proteins
      by virtue of the unique properties of lanthanides. Lanthanide-tagged proteins can
      be studied by NMR, X-ray, fluorescence, and EPR spectroscopy. However, the
      rigidity of a lanthanide tag in labeling of proteins plays a key role in the
      determination of protein structures and interactions. Pseudocontact shift (PCS)
      and paramagnetic relaxation enhancement (PRE) are valuable long-range structure
      restraints in structural-biology NMR spectroscopy. Generation of these
      paramagnetic restraints generally relies on site-specific tagging of the target
      proteins with paramagnetic species. To avoid nonspecific interaction between the
      target protein and paramagnetic tag and achieve reliable paramagnetic effects,
      the rigidity, stability, and size of lanthanide tag is highly important in
      paramagnetic labeling of proteins. Here 4'-mercapto-2,2':6',2''-terpyridine-6,6''
      dicarboxylic acid (4MTDA) is introduced as a a rigid paramagnetic and fluorescent
      tag which can be site-specifically attached to a protein by formation of a
      disulfide bond. 4MTDA can be readily immobilized by coordination of the protein
      side chain to the lanthanide ion. Large PCSs and RDCs were observed for 4MTDA
      tagged proteins in complexes with paramagnetic lanthanide ions. At an excitation
      wavelength of 340 nm, the complex formed by protein-4MTDA and Tb(3+) produces
      high fluorescence with the main emission at 545 nm. These interesting features of
      4MTDA make it a very promising tag that can be exploited in NMR, fluorescence,
      and EPR spectroscopic studies on protein structure, interaction, and dynamics.

PMID- 24307371
TI  - Formation of substituted oxa- and azarhodacyclobutanes.
AB  - The preparation of substituted oxa- and azarhodacyclobutanes is reported. After
      exchange of ethylene with a variety of unsymmetrically and symmetrically
      substituted alkenes, the corresponding rhodium-olefin complexes were oxidized
      with H2O2 and PhINTs (Ts=p-toluenesulfonyl) to yield the substituted oxa- and
      azarhodacyclobutanes, respectively. Oxarhodacyclobutanes could be prepared with
      excellent selectivity for incorporation of the oxygen atom on the more
      substituted carbon atom of the alkene. At the same time, azarhodacyclobutanes
      showed good-to-excellent selectivity for heteroatom incorporation on the less
      substituted carbon. Furthermore, it was shown that steric modifications of the
      ancillary ligand have a significant influence on the selectivity of Rh-olefin
      complex formation as well as formation of the substituted azametallacycles.

PMID- 24307372
TI  - Generation and spectroscopic identification of ClCNS, ClNCS and NCCNS.
AB  - The photolysis of four chloro-substituted thiadiazoles (3,4-dichloro-, 3-chloro-
      and 3-chloro-4-fluoro-1,2,5-thiadiazole; 3,5-dichloro-1,2,4-thiadiazole) and 3,4
      dicyano-1,2,5-thiadiazole was investigated in inert solid-argon matrices at
      cryogenic temperatures by means of UV irradiation at selected wavelengths of 254
      and 280 nm. The photolysis products were identified by mid-IR and UV
      spectroscopy. Evidence for the existence of three novel pseudohalides, namely,
      chloronitrile sulfide (ClCNS), chlorine isothiocyanate (ClNCS) and cyanogen N
      sulfide (NCCNS), was provided by direct spectroscopic methods supported by
      quantum chemical calculations. Ground-state geometries, vibrational frequencies,
      IR intensities, and UV excitation energies of ClCNS, ClNCS and NCCNS were
      obtained from calculations using the B3LYP, CCSD(T) and SAC-CI methods and the
      aug-cc-pV(T+d)Z basis set.

PMID- 24307373
TI  - The effect of the length of histone H3K4me3 on recognition by reader proteins.

PMID- 24307375
TI  - Robust diagnostic genetic testing using solution capture enrichment and a novel
      variant-filtering interface.
AB  - Targeted hybridization enrichment prior to next-generation sequencing is a
      widespread method for characterizing sequence variation in a research setting,
      and is being adopted by diagnostic laboratories. However, the number of variants
      identified can overwhelm clinical laboratories with strict time constraints, the
      final interpretation of likely pathogenicity being a particular bottleneck. To
      address this, we have developed an approach in which, after automatic variant
      calling on a standard unix pipeline, subsequent variant filtering is performed
      interactively, using AgileExomeFilter and AgilePindelFilter
      (http://dna.leeds.ac.uk/agile), tools designed for clinical scientists with
      standard desktop computers. To demonstrate the method's diagnostic efficacy, we
      tested 128 patients using (1) a targeted capture of 36 cancer-predisposing genes
      or (2) whole-exome capture for diagnosis of the genetically heterogeneous
      disorder primary ciliary dyskinesia (PCD). In the cancer cohort, complete
      concordance with previous diagnostic data was achieved across 793 variant
      genotypes. A high yield (42%) was also achieved for exome-based PCD diagnosis,
      underscoring the scalability of our method. Simple adjustments to the variant
      filtering parameters further allowed the identification of a homozygous
      truncating mutation in a presumptive new PCD gene, DNAH8. These tools should
      allow diagnostic laboratories to expand their testing portfolios flexibly, using
      a standard set of reagents and techniques. 

PMID- 24307374
TI  - Genetic evidence in planar cell polarity signaling pathway in human neural tube
      defects.
AB  - Neural tube defects (NTDs) are a group of birth anomalies having a profound
      physical, emotional, and financial effects on families and communities. Their
      etiology is complex, involving environmental and genetic factors that interact to
      modulate the incidence and severity of the developing phenotype. The planar cell
      polarity (PCP) pathway controls the process of convergent extension (CE) during
      gastrulation and neural tube closure and has been implicated in the pathogenesis
      of NTDs in animal models and human cohorts. This review summarizes the cumulative
      results of recent studies on PCP signaling pathway and human NTDs. These results
      demonstrate that PCP gene alterations contribute to the etiology of human NTDs. 

PMID- 24307376
TI  - Saturday night broad QRS complex tachycardia in a young male.

PMID- 24307377
TI  - Waterpipe smoking: not necessarily less hazardous than cigarette smoking :
      Possible consequences for (cardiovascular) disease.
AB  - CONTEXT: Cigarette smoking has declined over the last years in modern countries.
      On the contrary, waterpipe smoking has increased, especially among young people
      visiting waterpipe bars. Unfortunately, most waterpipe smokers seem to know
      little about the possible cardiovascular and other health consequences of
      waterpipe smoking. OBJECTIVE: To describe by narrative literature review the
      known adverse consequences for the human body caused by smoking the waterpipe
      compared with the consequences of smoking normal cigarettes. Also, to get a
      picture of public awareness of these consequences as deducted from the literature
      and a small new survey in the Netherlands. RESULTS/CONCLUSIONS: Tobacco smoking
      is associated with serious adverse (cardiovascular) health effects, and there is
      no evidence that these effects are less serious if a waterpipe is used. The
      increasing use together with the limited amount of awareness and attention for
      the possible health consequences of smoking the waterpipe is worrisome.
      Especially considering the increasing acceptance and use of the waterpipe among
      the youth. Therefore we recommend more systematic research into the possible
      health hazards of waterpipe smoking. In the meantime education campaigns and
      materials are needed to raise public awareness on the possible health risks of
      waterpipe use.

PMID- 24307378
TI  - Prevalence of psychological distress in elderly hypertension patients in primary
      care.
AB  - BACKGROUND: Recent guidelines on cardiovascular disease prevention advocate the
      importance of psychological risk factors, as they contribute to the risk of
      developing cardiovascular disease. However, most previous research on
      psychological distress and cardiovascular factors has focused on selected
      populations with cardiovascular disease. AIM: The primary aim was to determine
      the prevalence of depression, anxiety, and Type D personality in elderly primary
      care patients with hypertension. Secondary aim was to examine the relation
      between elevated systolic blood pressure and depression, anxiety, and Type D
      personality. DESIGN AND SETTING: A cross-sectional study in primary care
      practices located in the south of the Netherlands. METHOD: Primary care
      hypertension patients (N = 605), between 60 and 85 years (45 % men, mean age = 70
      +/- 6.6), were recruited for this study. All patients underwent a structured
      interview including validated self-report questionnaires to assess depression
      (PHQ-9), anxiety (GAD-7), and Type D personality (DS14) as well as blood pressure
      assessment. RESULTS AND CONCLUSION: Depression was prevalent in 5 %, anxiety in 5
      %, and Type D personality in 8 %. None of the distress measures were associated
      with elevated systolic blood pressure of >160 mmHg (all p-values >0.05). This
      study showed no relation between psychological distress and elevated systolic
      blood pressure in elderly primary care patients with hypertension.

PMID- 24307379
TI  - Association of TMV coat protein with chloroplast membranes in virus-infected
      leaves.
AB  - The polypeptide composition of extracts of chloroplasts from tobacco leaves
      systemically infected with different strains of Tobacco Mosaic Virus (TMV) was
      analyzed by one- and two-dimensional gel electrophoresis. There were no changes
      in the protein profiles of chloroplasts from infected leaves when compared to
      control leaves except for the presence of coat protein (CP) of TMV, identified by
      immunoblotting. When protease-treated intact chloroplasts isolated on Percoll
      gradients were osmotically disrupted the CP could be detected in both stroma and
      membrane fractions. The majority of the CP associated with the thylakoid
      membranes (about 1-5% of the total thylakoid proteins) was in the form of free
      molecules while stroma contained aggregated or assembled CP (about 0.1% of the
      soluble proteins). Thylakoid-associated CP was insensitive to protease digestion
      unless the membranes were first treated with a detergent, indicating that the CP
      was embedded inside or otherwise complexed with the thylakoid
      membranes.Chloroplasts isolated from leaves infected with TMV-PV42, a symptomless
      strain, contained approximately 10-50 times less CP than did chloroplasts
      isolated from leaves bearing mosaic symptoms induced by other strains of TMV (U1,
      PV230 or PV39). A possible role of CP in symptom development is discussed. 

PMID- 24307380
TI  - Genetic transformation of Brassica campestris var. rapa protoplasts with an
      engineered cauliflower mosaic virus genome.
AB  - A hybrid Cauliflower Mosaic Virus (CaMV) genome containing a selectable marker
      gene was constructed by replacing the gene VI coding region with the
      aminoglycoside (neomycin) phosphotransferase type II [APH(3')II] gene from Tn5.
      This modified viral genome was tested for its infectivity both in planta and in a
      protoplast transformation system of Brassica campestris var. rapa. Stable,
      genetically transformed cell lines of B. campestris var. rapa were obtained after
      transformation. DNA of the hybrid CaMV genome was found to be integrated into
      high molecular weight plant genomic DNA. Transformation was achieved only when
      the hybrid genome was supplied together with wild type viral DNA. A possible
      complementation of the modified CaMV genome with the wild type viral DNA as a
      helper molecule in planta and in the protoplast system is discussed. 

PMID- 24307381
TI  - A linear DNA molecule of 5.9 kilobase-pairs is highly homologous to the
      chloroplast DNA in the green alga Chlamydomonas moewusii.
AB  - The unicellular green alga Chlamydomonas moewusii contains small DNA species of
      unknown cellular location. We report that the most abundant of these DNAs, here
      designated low-molecular-weight DNA (LMW DNA), is a linear molecule of 5.9
      kilobase pairs (kbp). Southern blot hybridization and restriction enzyme analysis
      revealed that the LMW DNA sequence also exists as an integrated sequence in a
      discrete region of the chloroplast genome. We have confirmed earlier reports that
      small DNA species related to the LMW DNA are absent from Chlamydomonas eugametos,
      an alga which is interfertile with C. moewusii. In the C. eugametos chloroplast
      genome we found only remnants of the LMW DNA sequence. 

PMID- 24307382
TI  - Developmental regulation of RI TL-DNA gene expression in roots, shoots and tubers
      of transformed potato (Solanum tuberosum cv. Desiree).
AB  - Expression of TL-DNA from Agrobacterium rhizogenes plasmid pRi 1855 was examined
      in a transformed derivative of Solanum tuberosum cv. Desiree, D9X8a. Northern
      blot analysis identified at least nine TL-DNA coded transcripts in roots, shoots
      and tubers but their relative abundance differed within and between organs. This
      revealed a distinctive pattern of organ specified differential expression.
      Grafting experiments showed that the abnormal shape of tubers of transformed
      potato was probably determined by TL-DNA products synthesised within the tuber
      and not by diffusable products synthesised in other parts of the plant. The
      abundance of at least one transcript, tr5, was probably determined by culture
      conditions. Implications for functions and control of expression of Ri TL-DNA
      genes are discussed. It is suggested that Ri TL-DNA provides a convenient and
      extensive set of model genes to study variation and stability of expression of
      linked foreign genes introduced into plants. 

PMID- 24307383
TI  - Restriction endonuclease studies on the chloroplast and mitochondrial DNAs of
      alfalfa (Medicago sativa L.) protoclones.
AB  - Alfalfa protoclones were regenerated from the mesophyll protoplasts of two cloned
      source plants (parents), RS-K1 and RS-K2, initiated from Regen S seed. Because of
      the high frequency of karyotypic upset previously observed in these plants,
      chloroplast DNAs (cpDNA) from 23 protoclones and mitochondrial DNAs (mtDNA) from
      20 protoclones were examined by restriction endonuclease analysis in order to
      assess recombination in their cytoplasmic genomes. Seven and four endonucleases
      were separately used for cpDNA and mtDNA analysis, respectively. Data were
      consistent with no, or a low frequency of, major sequence rearrangements in
      either the chloroplast or the mitochondrial genomes as a result of protocloning.
      However, two types of cpDNA were detected in the 23 protoclones, with only one
      protoclone possessing the cpDNA type of the cloned parental populations sampled.
      Possible explanations include a preferential selection during protocloning for
      one of two parental cpDNA types, an in planta sorting out of cpDNA types in the
      parental material or both. 

PMID- 24307384
TI  - Variation in the ribosomal RNA genes among individuals of Vicia faba.
AB  - Length heterogeneity in the ribosomal repeat of Vicia faba is due to the presence
      of variable numbers of a 325 bp subrepetitive element within the nontranscribed
      spacer region. The distribution of size classes among 88 individuals within a
      population was investigated by blot-hybridization. We find that individual plants
      can exhibit more than 20 size classes and that hybridization patterns are highly
      diverse from individual to individual, more so than for any species so far
      investigated. In contrast, no such differences are observed in patterns for
      different tissues from a single plant or from parental to F1 generation. Some
      changes were observed in the F2 generation. We conclude that unequal
      recombination can give rise to the diversity that we observe for the V. faba rDNA
      repeats. 

PMID- 24307385
TI  - The expression of a nopaline synthase - human growth hormone chimaeric gene in
      transformed tobacco and sunflower callus tissue.
AB  - To study whether mammalian RNA processing signals function in plants, we have
      constructed a chimaeric gene in which the complete human growth hormone (hGH)
      gene is flanked by DNA fragments containing the promoter and polyadenylation site
      of the nopaline synthase gene. The hGH gene used contains four introns and an
      additional 440 bp downstream from the hGH poly(A) addition site. The
      transcription of this chimaeric gene was studied following its introduction into
      sunflower and tobacco cells using a Ti plasmid vector. Analysis of poly(A)(+) RNA
      isolated from the transformed tumor tissue demonstrated the following: (1) a
      single polyadenylated transcript, 2700 bp in length, was transcribed from the
      chimaeric gene; (2) the transcription was initiated at the published start site
      of the nopaline synthase gene; (3) the hGH polyadenylation site was not used for
      processing of the 3' end; only the poly(A) addition site of the nopaline synthase
      gene was recognized, (4) no splicing of the hGH introns could be detected. We
      also demonstrate that the hGH pre-mRNA isolated from plant cells can be spliced
      in a HeLa cell nuclear extract, indicating that the hGH pre-mRNA was functional.
      These results show that processing signals of the hGH pre-mRNA are not recognized
      in these plant cells. 

PMID- 24307387
TI  - Biotechnology news and views.

PMID- 24307386
TI  - Structure of a 3.2 kb region of pea chloroplast DNA containing the gene for the
      44 kD photosystem II polypeptide.
AB  - The gene for the 44 kD chlorophyll a-binding photosystem II polypeptide has been
      localized on the pea (Pisum sativum) chloroplast genome. The nucleotide sequence
      of the gene and its flanking regions has been analyzed. The gene codes for a
      polypeptide of 473 amino acid residues and is possibly cotranscribed with the
      gene for the D2 photosystem II polypeptide with which it has 50 bp in common. The
      amino acid sequences of the 44 kD polypeptides from pea, spinach and maize are
      approximately 95% homologous. Within the 1 kb fragment 3' to the 44 kD gene a 93
      bp tRNA-Ser (UGA) gene and an open reading frame of 62 codons (ORF 62) were
      identified. Both show high homology to corresponding genes 3' to the 44 kD genes
      from spinach, maize and barley. The 44 kD gene and ORF 62 are encoded in the same
      strand, and have putative promoter sequences, ribosome binding sites and
      transcription termination signals. 

PMID- 24307388
TI  - Leukemia inhibitory factor promotes porcine oocyte maturation and is accompanied
      by activation of signal transducer and activator of transcription 3.
AB  - We produced recombinant porcine leukemia inhibitory factor (pLIF) and examined
      its effect on in vitro maturation (IVM) of porcine oocytes and their
      developmental competence after in vitro fertilization. Porcine cumulus-oocyte
      complexes (COCs) were matured in a medium supplemented with pLIF during the first
      22 hr, last 22 hr, or entire 44 hr duration of IVM. Oocytes in all groups tended
      to show enhanced nuclear maturation rates by the metaphase II (MII) stage (76.1%,
      82.1%, and 86.6%, respectively) compared to the without-pLIF treatment group
      (69.6%, control). A significant increase in MII rate (P < 0.05) and obvious
      induction of cumulus expansion were observed over the whole time span (44 hr) in
      the IVM group. When cumulus cells were removed at 22 hr and denuded oocytes were
      further cultured, pLIF showed no effect on maturation rate. Oocytes matured in
      pLIF-supplemented medium showed a tendency for more rapid blastocyst development
      (21.1% vs. 16.2%, P = 0.0715). Examination of transcripts and proteins of the LIF
      signaling pathway in COCs revealed that LIF, LIF receptors, and signal transducer
      and activator of transcription 3 (STAT3) are present in both cumulus cells and
      oocytes. The amount of phosphorylated STAT3 (p-STAT3) markedly increased in both
      cumulus cells and oocytes cultured in pLIF-supplemented media, although oocyte p
      STAT3 disappeared after 44 hr of IVM. These results suggest that the LIF/STAT3
      pathway is functional during IVM of porcine oocytes, and supplementing pLIF in
      the IVM medium can improve oocyte maturation by activating this pathway.

PMID- 24307389
TI  - Pre-weaning growth performance of crossbred lambs (Dorper * indigenous sheep
      breeds) under semi-intensive management in eastern Ethiopia.
AB  - A study was conducted to assess the effect of genetic and non-genetic factors
      (litter size, sex of lamb, and parity of dam) on pre-weaning growth performance
      of crossbred lambs (75% Dorper (DR) 25% indigenous lambs; and 50% Dorper 50%
      indigenous lambs) under semi-intensive husbandry practices in eastern Ethiopia.
      Data from a total of 275 Dorper sire breed * indigenous (Blackhead Ogaden [BHO]
      and Hararghe Highland [HH]) crossbred lambs with different genetic group of the
      parental breeds were collected for three consecutive years (2009 to 2011). Pre
      weaning growth performance attributes of crossbred lambs studied were birth
      weight, weaning weight, and pre-weaning average daily gain. Data were analyzed
      using the GLM procedure of SAS (2003). Breed group and non-genetic factors
      significantly affected pre-weaning growth performance. Lambs with 75% Dorper and
      25% indigenous had higher (P < 0.01) birth weight than 50% DR and 50% HH but
      similar to 50% DR and 50% BHO. Weaning weight and pre-weaning live weight gain
      were higher (P < 0.01) for 3/4DR1/4BHO and 3/4DR1/4HH than 50% Dorper
      inheritance. Single-born lambs had higher weight at birth, weaning weight, and
      pre-weaning average daily gain as compared to twins. Sex comparison is
      significant (P < 0.05) and male lambs recorded highest pre-weaning growth
      performance compared to female counterparts. Parity, season, and lambing year
      significantly (P < 0.01) influenced the pre-weaning growth of crossbred lambs.
      Therefore, it could be concluded that 50-75% Dorper inheritance improved pre
      weaning growth performance of indigenous breeds of Hararghe Highland and
      Blackhead Ogaden sheep. The result also suggested culling of ewes older than
      fourth parity to improve the pre-weaning growth performance of lambs.

PMID- 24307390
TI  - Risk factors for anaplasmosis in dairy cows during the peripartum.
AB  - Anaplasma marginale is endemic in tropical and subtropical areas around the
      world. Some studies have suggested that cows during peripartum may present a
      transient immunosuppression state and development of clinical signs of
      anaplasmosis. The aim of this study was to investigate the relationship between
      some risk factors and the seroprevalence of A. marginale in dairy cows during
      peripartum in Rio de Janeiro, Brazil. The risk factors analyzed in association
      with the prevalence of antibodies against A. marginale in dairy cows were calving
      season, reproductive experience, breed standard, tick infestations, stocking
      density, and milk yield. The antibodies against A. marginale were tested in
      indirect enzyme-linked immunosorbent assays. A primary screening using a 2 * k
      contingency table of the exposed variables with the outcomes was performed. All
      variables for which p < 0.20 were included in a fixed effects log regression. The
      risk factors investigated to anaplasmosis were calving (OR 2.61, IC 1.08-7.63),
      breed standard (OR 3.83, IC 0.08-0.28), reproductive experience (OR 33.7, IC 2.14
      5.16), milk yield (OR 3.9, IC 2.24-7.03), Rhipicephalus microplus infestations
      (OR 10.3, IC 0.05-0.17), and stocking density (OR 22.3, IC 0.05-0.17). Low titers
      of antibodies against A. marginale during peripartum had been characterized as a
      period previous to development of clinical anaplasmosis. Thus, studies on
      anaplasmosis should consider each farm as an epidemiological unit, where
      environmental and immunological factors may influence the endemic status of the
      pathogen.

PMID- 24307392
TI  - And the winner is...azadithiolate: an amine proton relay in the [FeFe]
      hydrogenases.
AB  - A victory in the pocket: An international team of chemists and biophysicists have
      resolved the long-standing question of the structure of the active site of the
      [FeFe] hydrogenases by assembling the active enzyme with a version of the active
      site synthesized in vitro (see scheme; HydF is a scaffold protein, HydA1 is a
      natural hydrogenase). The protein incorporating the diiron complex 2 showed
      similar activity to that of the natural enzyme. 

PMID- 24307391
TI  - Seroprevalence and risk factors associated with Chlamydophila spp. infection in
      ewes in the northeast of Algeria.
AB  - A cross-sectional study was carried out to estimate prevalence of Chlamydophila
      spp. antibodies and to investigate risk factors associated with chlamydial
      infection in 552 ewes between March 2011 and January 2012 in the province of
      Constantine. Anti-Chlamydophila antibodies were detected using an indirect enzyme
      linked immunosorbent assay kit in 24.5% of examined sera. Of the herds, 70.4% had
      at least one seropositive animal. A pretested structured questionnaire was
      administered in order to collect information on individual animal health and herd
      management practices. Chi-square analysis and multivariable logistic regression
      model were used to identify risk factors related to Chlamydophila seropositivity.
      Univariable analysis revealed 17 variables with p < 0.25 that were offered to the
      multivariable logistic regression model which in turn identified 12-23 months age
      group (OR = 5.903, 95% CI (OR) = 1.690; 20.618) and not using disinfectants (OR =
      2.099, 95% CI (OR) = 1.314; 8.065) as risk factors for Chlamydophila spp.
      seropositivity. Moreover, occurrence of stillbirth problem (OR = 3.682, 95% CI
      (OR) = 1.825; 7.430) and 5-10% mortality rate in young lambs (OR = 2.584, 95% CI
      (OR) = 1.058; 6.310) were significantly associated with seropositivity to
      Chlamydophila spp. On the other hand, availability of veterinary service was
      identified as a protective factor (OR = 0.161, 95% CI (OR) = 0.051; 0.511).

PMID- 24307393
TI  - Next generation sequencing in nonsyndromic intellectual disability: from a
      negative molecular karyotype to a possible causative mutation detection.
AB  - The identification of causes underlying intellectual disability (ID) is one of
      the most demanding challenges for clinical Geneticists and Researchers. Despite
      molecular diagnostics improvements, the vast majority of patients still remain
      without genetic diagnosis. Here, we report the results obtained using Whole Exome
      and Target Sequencing on nine patients affected by isolated ID without
      pathological copy number variations, which were accurately selected from an
      initial cohort of 236 patients. Three patterns of inheritance were used to search
      for: (1) de novo, (2) X-linked, and (3) autosomal recessive variants. In three of
      the nine proband-parent trios analyzed, we identified and validated two de novo
      and one X-linked potentially causative mutations located in three ID-related
      genes. We proposed three genes as ID candidate, carrying one de novo and three X
      linked mutations. Overall, this systematic proband-parent trio approach using
      next generation sequencing could explain a consistent percentage of patients with
      isolated ID, thus increasing our knowledge on the molecular bases of this disease
      and opening new perspectives for a better diagnosis, counseling, and treatment.

PMID- 24307394
TI  - Oncological translational research in the Spanish national health system: the
      INTRO study.
AB  - OBJECTIVES: Under the auspices of the Foundation for Excellence and Quality in
      Oncology (ECO), the Translational Research in Oncology Medical Services Study
      (INTRO) was conducted with the aim of describing the current state of, and future
      expectations for translational cancer research in Spanish medical centres. The
      first step in the investigation was intended to analyse the current condition of
      the national Medical Oncology Services network by examining different aspects of
      the oncology research field. METHODS: A descriptive and observational multicentre
      study was performed at a statewide level; information was collected by surveying
      a cross-section of all those responsible for Medical Oncology Services in Spain.
      RESULTS: The survey was completed by key informants, who were selected
      independently by each service, between September 2010 and April 2011. We were
      able to gather comprehensive data from a total of 27 Spanish hospitals. These
      data enabled us to describe the allocation of human and material resources
      devoted to clinical and translational research across the Medical Oncology
      Services and to describe the organisational and functional components of these
      services and units. These data included information pertaining to the activities
      developed, their funding sources, and their functional dependence on other
      internal or external bodies. Finally, we explored the degree of dissemination and
      use of some specific techniques used for the genetic diagnosis of cancer, which
      have recently been introduced in Medical Oncology within the Spanish healthcare
      system. CONCLUSIONS: A wide range of variability exists between different
      oncology services in Spanish hospitals. Time should be spent reflecting on the
      need and opportunities for improvement in the development of translational
      research within the field of oncology.

PMID- 24307396
TI  - Non-homologous end joining-mediated functional marker selection for DNA cloning
      in the yeast Kluyveromyces marxianus.
AB  - The cloning of DNA fragments into vectors or host genomes has traditionally been
      performed using Escherichia coli with restriction enzymes and DNA ligase or
      homologous recombination-based reactions. We report here a novel DNA cloning
      method that does not require DNA end processing or homologous recombination, but
      that ensures highly accurate cloning. The method exploits the efficient non
      homologous end-joining (NHEJ) activity of the yeast Kluyveromyces marxianus and
      consists of a novel functional marker selection system. First, to demonstrate the
      applicability of NHEJ to DNA cloning, a C-terminal-truncated non-functional ura3
      selection marker and the truncated region were PCR-amplified separately, mixed
      and directly used for the transformation. URA3(+) transformants appeared on the
      selection plates, indicating that the two DNA fragments were correctly joined by
      NHEJ to generate a functional URA3 gene that had inserted into the yeast
      chromosome. To develop the cloning system, the shortest URA3 C-terminal encoding
      sequence that could restore the function of a truncated non-functional ura3 was
      determined by deletion analysis, and was included in the primers to amplify
      target DNAs for cloning. Transformation with PCR-amplified target DNAs and C
      terminal truncated ura3 produced numerous transformant colonies, in which a
      functional URA3 gene was generated and was integrated into the chromosome with
      the target DNAs. Several K. marxianus circular plasmids with different selection
      markers were also developed for NHEJ-based cloning and recombinant DNA
      construction. The one-step DNA cloning method developed here is a relatively
      simple and reliable procedure among the DNA cloning systems developed to date.

PMID- 24307397
TI  - Should water precautions be recommended for children with tympanostomy tubes?

PMID- 24307395
TI  - Epidermal growth factor receptor tyrosine-kinase inhibitor treatment resistance
      in non-small cell lung cancer: biological basis and therapeutic strategies.
AB  - Lung cancer remains the leading cause of cancer-related death. Non-small cell
      lung cancer (NSCLC) represents 85 % of all lung cancer cases and it is classified
      into three major subtypes: adenocarcinoma, squamous cell carcinoma and large-cell
      carcinoma. In the past years, molecular-targeted therapies have been developed in
      order to improve response, survival and quality of life in patients with advanced
      NSCLC. Lung cancers harboring mutations in the epidermal growth factor receptor
      (EGFR) respond to EGFR tyrosine-kinase inhibitors (TKIs). However, virtually all
      patients with initial response relapse due to acquired resistance. Better
      understanding the biology of these tumors and mechanisms of EGFR TKIs resistance
      could shed some light on research of new therapeutic options in this setting.
      This review aims to emphasize on EGFR involved lung cancer pathway, primary and
      acquired mechanisms of TKIs resistance, and discuss agents currently used in
      clinical development in this emerging scenario. 

PMID- 24307398
TI  - A standardized online clinical education and assessment tool for neurology
      clerkship students assigned to multiple sites.
AB  - The Drexel neurology clerkship experience can vary from large groups at a
      university hospital inpatient unit to smaller groups at private physician
      offices. Evaluations are based on the site director's subjective assessment and
      performance on the National Board of Medical Examiners neurology shelf
      examination. We are developing a standardized online clinical neurology course
      and quiz for the whole clerkship. We piloted the course and quiz at a single site
      for one academic year and compared their test scores with a control group of
      students at other clerkship sites who took the online quiz without viewing the
      course. Students at the pilot site achieved higher scores both on the neurology
      shelf examination and the clinical quiz and also reported higher teaching
      satisfaction scores than students at all other sites. There was a 97 %
      participation rate in the online quiz from the other sites. Use of this online
      course and quiz provides effective standardized clinical neurology teaching and
      evaluation that can be applied to students across multiple sites. 

PMID- 24307399
TI  - Focus on international research strategy and teaching: the FIRST programme.
AB  - Research, education and patient care are important missions of academic health
      centres and their respective teaching programmes. Yet, teaching hospitals
      struggle with ways to effectively support quality research initiatives. These
      issues are even more pronounced in countries with developing medical education
      systems where inconsistencies in training programme structure and quality, along
      with the lack of uniformity in the backgrounds and experience of the faculty, can
      hinder meaningful research activities. Hospital leaders recognized the need to
      inculcate both the desire and the ability to conduct quality research into every
      postgraduate training programme. Given the lack of global benchmarks, the
      institution developed and implemented the FIRST Programme (Focus on International
      Research Strategy and Teaching), a hospital-wide approach to research strategy
      training and support in 2010-2012. Over a 3-year period, the number of resident
      and faculty research activities has more than doubled. The types of research
      studies have also changed over the past few years, with an increase in basic
      science and randomized clinical trials. Our experience with implementing an
      institution-wide research initiative has been quite encouraging. Through
      leadership commitment, the institution has witnessed substantial increases in
      both trainee and faculty scholarship over a 3-year period. 

PMID- 24307400
TI  - Endoscopist-related factors contributing to high-quality colonoscopy: results of
      a Delphi survey.
AB  - Education and competency assessment in gastrointestinal endoscopy is important.
      Concerning colonoscopy, it is not completely clear what the best way is to learn
      this procedure, what defines competency in colonoscopy, and which factors define
      a high-quality colonoscopy. The aim of this study was to determine the
      endoscopist-related factors that define a high-quality colonoscopy. A three-round
      Delphi survey among expert endoscopists was carried out. In round 1, the panel
      was invited to identify factors essential for a good colonoscopy. The listed
      factors were to be ranked during the second round. In the third round, a 5-point
      Likert scale was added. A reference panel was invited to assess the items as
      well. 14 expert endoscopists from the Netherlands were invited, of whom eight
      participated (57 %). A list of 30 items important for colonoscopy was formulated.
      After the following rounds, consensus was reached on 16 items. Validation was
      conducted among eight trainees and eight experienced endoscopists (response 100
      %). The groups agreed on the importance of all but one factor (p = 0.001). This
      Delphi survey has made explicit the endoscopist-related factors that are
      important for optimal colonoscopy. This might provide trainers more support
      regarding concrete competency assessment of trainees in endoscopy. 

PMID- 24307401
TI  - Self-assembly of hierarchical nanostructures from dopamine and polyoxometalate
      for oral drug delivery.
AB  - The preparation of 3D hierarchical nanostructures by a simple and versatile
      strategy of self-assembly of dopamine (DA) and phosphotungstic acid (PTA) is
      described. The size and morphology of the hierarchical nanostructures could be
      simply controlled by varying the ratio of the two components, their
      concentrations, and the pH of the initial Tris-HCl solution. The self-assembly of
      the flowerlike microspheres has been found to involve a two-stage growth process.
      Moreover, use of the hierarchical nanostructures as a possible carrier for an
      anticancer drug in chemotherapy has been explored. The nanostructures showed an
      intriguing pH-dependent release behavior, making them promising for applications
      in biomedical science. 

PMID- 24307402
TI  - The N-terminus and Tudor domains of Sgf29 are important for its heterochromatin
      boundary formation function.
AB  - Eukaryotic chromosomes are organized into heterochromatin and euchromatin
      domains. Heterochromatin domains are transcriptionally repressed and prevented
      from spreading into neighbouring genes by chromatin boundaries. Previously, we
      identified 55 boundary-related genes in Saccharomyces cerevisiae. In this study,
      we describe the characterization of one of these boundary genes, named SGF29,
      which was previously reported as a component of the SAGA, SLIK, ADA and HAT-A2
      complex. A domain analysis of Sgf29 identified two minimal regions that can
      function as individual boundaries. The N-terminal minimal region comprising amino
      acids 1-12, which has not been defined as a functional domain, showed stronger
      boundary formation ability than the C-terminal minimal region comprising amino
      acids 110-255, which contains Tudor domains. Together with Ada2, Ada3 and Sgf29,
      which are all components of SAGA, Gcn5 acetylates multiple lysine residues on
      nucleosomal histone H3, which is associated with an open chromatin structure.
      However, the results presented in this study suggest that the boundary formation
      ability of the Sgf29 minimal regions is independent of Gcn5. An in vivo analysis
      also revealed that Sgf29 and Gcn5 perform distinct functions at native telomere
      boundary regions on the chromosome. 

PMID- 24307403
TI  - Structure and properties of the C-terminal beta-helical domain of VgrG protein
      from Escherichia coli O157.
AB  - The bacterial Type 6 secretion system (T6SS) translocates protein toxins (also
      called effectors) from the cytosol of a T6SS-carrying cell to a target cell by a
      syringe-like supramolecular complex resembling a contractile tail of
      bacteriophages. Valine-glycine repeat protein G (VgrG) proteins, which are the
      homologues of the gp27-gp5 (gene product) cell puncturing complex of
      bacteriophage T4, are considered to be located at the attacking tip of the
      bacterial T6SS apparatus. Here, we over-expressed six VgrG proteins from
      pathogenic Escherichia coli O157 and CFT073 strains. Purified VgrG1 of E. coli
      O157 and c3393 of E. coli CFT073 form trimer in solution and are rich in beta
      structure. We also solved the crystal structure of a trypsin-resistant C-terminal
      fragment of E. coli O157 VgrG1 (VgrG1C(G561)) at 1.95 A resolution. VgrG1C(G561)
      forms a three-stranded antiparallel beta-helix which is structurally similar to
      the beta-helix domain of the central spike protein (gp138) of phi92 phage,
      indicating a possible evolutional relationship. Comparison of four different
      three-stranded beta-helix proteins shows how their amino acid composition
      determines the protein fold. 

PMID- 24307405
TI  - Structurally stabilized organosilane-templated thermostable mesoporous titania.
AB  - Structurally thermostable mesoporous anatase TiO2 (m-TiO2) nanoparticles,
      uniquely decorated with atomically dispersed SiO2, is reported for the first
      time. The inorganic Si portion of the novel organosilane template, used as a
      mesopores-directing agent, is found to be incorporated in the pore walls of the
      titania aggregates, mainly as isolated sites. This is evident by transmission
      electron microscopy and high-angle annular dark field scanning transmission
      electron microscopy, combined with electron dispersive X-ray spectroscopy. This
      type of unique structure provides exceptional stability to this new material
      against thermal collapse of the mesoporous structure, which is reflected in its
      high surface area (the highest known for anatase titania), even after high
      temperature (550  degrees C) calcination. Control of crystallite size, pore
      diameter, and surface area is achieved by varying the molar ratios of the
      titanium precursor and the template during synthesis. These mesoporous materials
      retain their porosity and high surface area after template removal and further
      NaOH/HCl treatment to remove silica. We investigate their performance for dye
      sensitized solar cells (DSSCs) with bilayer TiO2 electrodes, which are prepared
      by applying a coating of m-TiO2 onto a commercial titania (P25) film. The high
      surface area of the upper mesoporous layer in the P25-m-TiO2 DSSC significantly
      increases the dye loading ability of the photoanode. The photocurrent and fill
      factor for the DSSC with the bilayer TiO2 electrode are greatly improved. The
      large increase in photocurrent current (ca. 56%) in the P25-m-TiO2 DSSC is
      believed to play a significant role in achieving a remarkable increase in the
      photovoltaic efficiency (60%) of the device, compared to DSSCs with a monolayer
      of P25 as the electrode.

PMID- 24307406
TI  - Quantifying nanoscale biochemical heterogeneity in human epithelial cancer cells
      using combined AFM and PTIR absorption nanoimaging.
AB  - Subcellular chemical heterogeneity plays a key role in cell organization and
      function. However the biomechanics underlying the structure-function relationship
      is governed by cell substructures which are poorly resolved using conventional
      chemical imaging methods. To date, advances in sub-diffraction limited infrared
      (IR) nanoscopy have permitted intracellular chemical mapping. In this work we
      report how image analysis applied to a combination of IR absorption nanoimaging
      and topographic data permits quantification of chemical complexity at the
      nanoscale, enabling the analysis of biochemical heterogeneity in mammalian cancer
      cells on the scale of subcellular features.

PMID- 24307407
TI  - Editorial: Special issue on computational approaches for extracting knowledge
      from biological networks.

PMID- 24307404
TI  - Novel dynein DYNC1H1 neck and motor domain mutations link distal spinal muscular
      atrophy and abnormal cortical development.
AB  - DYNC1H1 encodes the heavy chain of cytoplasmic dynein 1, a motor protein complex
      implicated in retrograde axonal transport, neuronal migration, and other
      intracellular motility functions. Mutations in DYNC1H1 have been described in
      autosomal-dominant Charcot-Marie-Tooth type 2 and in families with distal spinal
      muscular atrophy (SMA) predominantly affecting the legs (SMA-LED). Recently,
      defects of cytoplasmic dynein 1 were also associated with a form of mental
      retardation and neuronal migration disorders. Here, we describe two unrelated
      patients presenting a combined phenotype of congenital motor neuron disease
      associated with focal areas of cortical malformation. In each patient, we
      identified a novel de novo mutation in DYNC1H1: c.3581A>G (p.Gln1194Arg) in one
      case and c.9142G>A (p.Glu3048Lys) in the other. The mutations lie in different
      domains of the dynein heavy chain, and are deleterious to protein function as
      indicated by assays for Golgi recovery after nocodazole washout in patient
      fibroblasts. Our results expand the set of pathological mutations in DYNC1H1,
      reinforce the role of cytoplasmic dynein in disorders of neuronal migration, and
      provide evidence for a syndrome including spinal nerve degeneration and brain
      developmental problems. 

PMID- 24307408
TI  - Detecting protein complexes based on relevancy from protein interaction networks.
AB  - In protein-protein interaction networks, proteins combine into macromolecular
      complexes to execute essential functions in the cells, such as replication,
      transcription, protein transport. To solve the problem of detecting protein
      complexes from protein interaction networks, we used relevant graph and
      irrelevant graph to represent the relation of connection between a node and a
      core graph. We defined a variable Relevancy to represent whether a node had a
      dense or loose connection to a core graph. Then we proposed the Relevancy
      Judgment algorithm to detecting protein complexes from protein interaction
      networks. Our algorithm decided whether a node belonged to a protein complex
      through judging the relevancy between core graph and nodes out of core graph.
      Experiment results show that our algorithm has an excellent performance in both
      accuracy and hit rate. 

PMID- 24307409
TI  - A computational model for genetic and epigenetic signals in colon cancer.
AB  - Cancer, a class of diseases, characterized by abnormal cell growth, has one of
      the highest overall death rates world-wide. Its development has been linked to
      aberrant genetic and epigenetic events, affecting the regulation of key genes
      that control cellular mechanisms. However, a major issue in cancer research is
      the lack of precise information on tumour pathways; therefore, the delineation of
      these and of the processes underlying disease proliferation is an important area
      of investigation. A computational approach to modelling malignant system events
      can help to improve understanding likely "triggers", i.e. initiating abnormal
      micro-molecular signals that occur during cancer development. Here, we introduce
      a network-based model for genetic and epigenetic events observed at different
      stages of colon cancer, with a focus on the gene relationships and tumour
      pathways. Additionally, we describe a case study on tumour progression recorded
      for two gene networks on colon cancer, carcinoma in situ. Our results to date
      showed that tumour progression rate is higher for a small, closely-associated
      network of genes than for a larger, less-connected set; thus, disease development
      depends on assessment of network properties. The current work aims to provide
      improved insight on the way in which aberrant modifications characterize cancer
      initiation and progression. The framework dynamics are described in terms of
      interdependencies between three main layers: genetic and epigenetic events, gene
      relationships and cancer stage levels. 

PMID- 24307410
TI  - OntoPIN: an ontology-annotated PPI database.
AB  - Protein-protein interaction (PPI) data stored in publicly available databases are
      queried by the use of simple query interfaces allowing only key-based queries. A
      typical query on such databases is based on the use of protein identifiers and
      enables the retrieval of one or more proteins. Nevertheless, a lot of biological
      information is available and is spread on different sources and encoded in
      different ontologies such as Gene Ontology. The integration of existing PPI
      databases and biological information may result in richer querying interfaces and
      successively could enable the development of novel algorithms that may use
      biological information. The OntoPIN project showed the effectiveness of the
      introduction of a framework for the ontology-based management and querying of
      Protein-Protein Interaction Data. The OntoPIN framework first merges PPI data
      with annotations extracted from existing ontologies (e.g. Gene Ontology) and
      stores annotated data into a database. Then, a semantic-based query interface
      enables users to query these data by using biological concepts. OntoPIN allows:
      (a) to extend existing PPI databases by using ontologies, (b) to enable a key
      based querying of annotated data, and (c) to offer a novel query interface based
      on semantic similarity among annotations. 

PMID- 24307411
TI  - Survey: Enhancing protein complex prediction in PPI networks with GO similarity
      weighting.
AB  - Predicting protein complexes from protein-protein interaction (PPI) networks has
      been the focus of many computational approaches over the last decade. These
      methods tend to vary in performance based on the structure of the network and the
      parameters provided to the algorithm. Here, we evaluate the merits of enhancing
      PPI networks with semantic similarity edge weights using Gene Ontology (GO) and
      its annotation data. We compare the cluster features and predictive efficacy of
      six well-known unweighted protein complex detection methods (Clique Percolation,
      MCODE, DPClus, IPCA, Graph Entropy, and CoAch) against updated weighted
      implementations. We conclude that incorporating semantic similarity edge
      weighting in PPI network analysis unequivocally increases the performance of
      these methods. 

PMID- 24307412
TI  - Mining maximal cohesive induced subnetworks and patterns by integrating
      biological networks with gene profile data.
AB  - With the availability of vast amounts of protein-protein, protein-DNA
      interactions, and genome-wide mRNA expression data for several organisms,
      identifying biological complexes has emerged as a major task in systems biology.
      Most of the existing approaches for complex identification have focused on
      utilizing one source of data. Recent research has shown that systematic
      integration of gene profile data with interaction data yields significant
      patterns. In this paper, we introduce the problem of mining maximal cohesive
      subnetworks that satisfy user-defined constraints defined over the gene profiles
      of the reported subnetworks. Moreover, we introduce the problem of finding
      maximal cohesive patterns which are sets of cohesive genes. Experiments on Yeast
      and Human datasets show the effectiveness of the proposed approach by assessing
      the overlap of the discovered subnetworks with known biological complexes.
      Moreover, GO enrichment analysis shows that the discovered subnetworks are
      biologically significant. 

PMID- 24307413
TI  - AutoSPET: an SPM plugin to automatize neuroimages PET analysis.
AB  - Neuroimaging analysis supports clinicians in the diagnosis of neurological
      diseases by extracting information from digital images. Due to the large number
      of images generated by new devices (e.g. PET ones), there is a lot of effort in
      defining computer-based tools to analyze and classify (brain) radiological
      images. Statistical tools, such as SPM (for Statistical Parametric Mapping), are
      largely used by physicians for image analysis. Nevertheless, large datasets
      analysis requires repetitive steps, due to the lack of automatic procedures. E.g.
      SPM requires human intervention during long and complex steps.We here present a
      tool, called AutoSPET (for Automatic SPM analysis for PET images), which allows
      to perform SPM analyses on large sets of PET images. It works as a meta-component
      orchestrating interactions with SPM, Matlab and with SPM plugins via a unified
      user interface. AutoSPET has been tested with real clinical datasets and it is
      publicly available as an official SPM plugin on the SPM website. 

PMID- 24307414
TI  - Building and mining web-based questionnaires and surveys with SySQ.
AB  - A questionnaire is a method for collecting data that can come from many sources
      such as observations, telephone interviews or documentary sources. Whatever the
      source of data is, the questionnaire provides a framework of questions that
      facilitate researcher's work. A manual approach for collecting data using
      questionnaire presents some limitations and introduces several sources of errors.
      A second issue regards the statistical and data mining of data that often is
      conducted using different tools than the questionnaire system, which may
      introduce errors in the analysis pipeline. For instance, common methods applied
      to data set concern the normality test, the association and correlation
      discovery, linear regression, classification and clustering. Usually this
      analysis is performed using external tools, often not free, such as SPSS, SAS,
      STATA, Weka, or Clementine.We present a web-based software system, to automatize
      the analysis pipeline and to support researchers involved in the collection of
      questionnaire data, such as in epidemiology, aiming to reduce the errors listed
      above and including some basic functions to conduct statistical analysis on
      collected data. Our system allows researchers to create questionnaires, adding
      sections and structured questions. It provides a preview of the questionnaire,
      the exportation of saved data into statistical software compatible formats, or it
      permits to analyze them directly applying statistical methods and common data
      mining techniques from the main interface. 

PMID- 24307416
TI  - DNA sequence organization in the genomes of three related millet plant species.
AB  - A major portion of the genomes of three millet species, namely, barn yard millet,
      fox tail millet and little millet has been shown to consist of interspersed
      repeat and single copy DNA sequences. The interspersed repetitive DNA sequences
      are both short (0.15-1.0 kilo base pairs, 62-64% and long (>1.5 kilo base pairs,
      36-38%) in barn yard millet and little millet while in fox tail millet, only long
      interspersed repeats (>1.5 kilo base pairs) are present. The length of the
      interspersed single copy DNA sequences varies in the range of 1.6-2.6 kilo base
      pairs in all the three species. The repetitive duplexes isolated after
      renaturation of 1.5 kilo base pairs and 20 kilo base pairs long DNA fragments
      exhibit a high thermal stability with Tms either equal to or greater than the
      corresponding native DNAs. The S1 nuclease resistant repetitive DNA duplexes also
      are thermally stable and reveal the presence of only 1-2% sequence divergence.The
      present data on the modes of sequence arrangement in millets substantiates the
      proposed trend in plants, namely, plants with 1C nuclear DNA content of less than
      5 picograms have diverse patterns of sequence organization while those with 1C
      nuclear DNA content greater than 5 picograms have predominantly a short period
      interspersion pattern. 

PMID- 24307415
TI  - Inhibition of peroxisome proliferator-activated receptor gamma: a potential link
      between chronic maternal hypoxia and impaired fetal growth.
AB  - Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized
      by maternal vascular dysfunction and diminished fetal growth. In an effort to
      identify novel pathways for these hypoxia-related effects, we assessed gene
      expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from
      43 female, high-altitude or sea-level residents in the nonpregnant state or
      during pregnancy (20 or 36 wk). Hypoxia-related fetal growth restriction becomes
      apparent between 25 and 29 wk of gestation and continues until delivery. Our
      sampling strategy was designed to capture changes occurring before (20 wk) and
      during (36 wk) the time frame of slowed fetal growth. PBMC gene expression
      profiles were generated using human gene expression microarrays and compared
      between altitudes. Biological pathways were identified using pathway analysis.
      Modest transcriptional differences were observed between altitudes in the
      nonpregnant state. Of the genes that were differentially expressed at high
      altitude vs. sea level during pregnancy (20 wk: 59 probes mapped to 41 genes; 36
      wk: 985 probes mapped to 700 genes), several are of pathological relevance for
      fetal growth restriction. In particular, transcriptional changes were consistent
      with the negative regulation of peroxisome proliferator-activated receptor gamma
      (PPARgamma) at high altitude; such effects were accompanied by reduced birth
      weight (P <0.05) and head circumference (P <0.01) at high altitude vs. sea level.
      Our findings indicate that chronic exposure to hypoxia during pregnancy alters
      maternal gene expression patterns in general and, in particular, expression of
      key genes involved in metabolic homeostasis that have been proposed to play a
      role in the pathophysiology of fetal growth restriction.

PMID- 24307417
TI  - Nodulation of specific legumes is controlled by several distinct loci in
      Rhizobium trifolii.
AB  - Three distinct loci (designated regions III, IV and V) were identified in the 14
      kb Nod region of Rhizobium trifolii strain ANU843 and were found to determine the
      host range characteristics of this strain. Deletion of region III or region V
      only from the 14 kb Nod region affected clover nodulation capacity. The
      introduction to R. Leguminosarum of DNA fragments on multicopy vectors carrying
      regions III, IV and V (but not smaller fragments) extended the host range of R.
      leguminosarum so that infection threads and nodules occurred on white clover
      plants. The same DNA fragments were introduced to the Sym plasmid-cured strain
      (ANU845) carrying the R. meliloti recombinant nodulation plasmid pRmSL26. Plasmid
      pRmSL26 alone does not confer root hair curling or nodulation on clover plants.
      However, the introduction to ANU845 (pRmSL26) of a 1.4 kb fragment carrying R.
      trifolii region IV only, resulted in the phenotypic activation of marked root
      hair curling ability to this strain on clovers but no infection events or nodules
      resulted. Only the transfer of regions III, IV and V to strain ANU845 (pRmSL26)
      conferred normal nodulation and host range ability of the original wild type R.
      trifolii strain. These results indicate that the host range genes determine the
      outcome of early plant-bacterial interactions primarily at the stage of root hair
      curling and infection. 

PMID- 24307418
TI  - A disarmed binary vector from Agrobacterium tumefaciens functions in
      Agrobacterium rhizogenes : Frequent co-transformation of two distinct T-DNAs.
AB  - Binary Ti plasmid vector systems consist of two plasmids in Agrobacterium, where
      one plasmid contains the DNA that can be transferred to plant cells and the other
      contains the virulence (vir) genes which are necessary for the DNA transfer but
      are not themselves stably transferred. We have constructed two nononcogenic
      vectors (pARC4 and pARC8) based on the binary Ti plasmid system of Agrobacterium
      tumefaciens for plant transformation. Each vector contains the left and right
      termini sequences from pTiT37. These sequences, which determine the extent of DNA
      transferred to plant cells, flank unique restriction enzyme sites and a marker
      gene that functions in the plant (nopaline synthase in pARC4 or neomycin
      phosphotransferase in pARC8). After construction in vitro, the vectors can be
      conjugatively transferred from E. coli to any of several Agrobacterium strains
      containing vir genes. Using A. rhizogenes strain A4 containing the resident Ri
      plasmid plus a vector with the nopaline synthase marker, we found that up to 50%
      of the hairy roots resulting from the infection of alfalfa or tomato synthesized
      nopaline. Thus, vector DNA encoding an unselected marker was frequently co
      transferred with Ri plasmid DNA to an alfalfa or a tomato cell. In contrast, the
      frequency of co-transfer to soybean cells was difficult to estimate because we
      encountered a high background of non-transformed roots using this species. Up to
      five copies of the vector DNA between the termini sequences were faithfully
      transferred and maintained in most cases suggesting that the termini sequences
      and the vir genes from the Ri and Ti plasmids are functionally equivalent. 

PMID- 24307419
TI  - A DNA topoisomerase type I from wheat embryo mitochondria.
AB  - In order to study DNA replication and expression in wheat mitochondria our
      laboratory has been seeking to develop a system that supports DNA synthesis and
      transcription, either in isolated mitochondria from wheat embryos or in a
      mitochondrial lysate from the same source deprived of endogenous DNA in vitro. We
      have characterized some of the enzymes involved in the DNA synthesis and
      transcription process. In this study we describe a DNA topoisomerase
      activity.Broken mitochondria from wheat embryos can actively relax negatively
      supercoiled DNA (pBR322, pAT153, etc...). The enzyme is intramitochondrial: the
      activity is detected only when intact organelles are broken by non-ionic
      detergent. Most of the topoisomerase activity found in the broken mitochondria is
      recovered in the mitochondrial lysate. It is stimulated by Mg(2+) and has an
      optimum salt concentration, KCl or NaCl, between 50 mM and 100 mM. ATP has no
      effect on this activity. Ethidium bromide, berenil, novobiocine and nalidixic
      acid, compounds currently used to characterize DNA topoisomerases, do not effect
      the relaxation of supercoiled DNA by the wheat mitochondrial activity. On the
      other hand N-ethylmaleimide has a strong inhibitory effect indicating that
      sulfhydryl groups are essential for enzyme activity. The molecular weight of the
      enzyme as determined by glycerol gradient sedimentation, is about 110 kd. Another
      important feature of the mitochondrial lysate DNA topoisomerase is the ability to
      relax positively supercoiled DNA, a property of eukaryotic topoisomerases I. 

PMID- 24307420
TI  - Specific in vitro transcription of 16S rRNA gene by pea chloroplast RNA
      polymerase.
AB  - A highly purified RNA polymerase preparation from pea chloroplasts has been shown
      to specifically transcribe the 16S rRNA gene in vitro using the recombinant pCB2
      8 DNA as a template. The RNA polymerase has been found to show maximum activity
      and specificity with pea supercoiled rDNA as a template. At low concentrations of
      ribonucleoside triphosphates, the RNA polymerase selectively initiates
      transcription on the 16S rRNA gene. A part of the 16S rRNA gene has been
      sequenced. The mature 16S rRNA has been found by S1 nuclease analysis to contain
      sequences starting from GAAGCT. The in vitro synthesized RNA has been found to
      protect the same nucleotides GAAGCT. In addition, the in vitro synthesized RNA
      was also found to strongly protect bases starting with TATG located at about 260
      bases away from the start site of the mature 16S rRNA. 

PMID- 24307421
TI  - Insertion of the Mu1 transposable element into the first intron of maize Adh1
      interferes with transcript elongation but does not disrupt chromatin structure.
AB  - The presence of the Mu1 transposable element within the first intervening
      sequence of the maize Adh1 gene interfered with transcription through that gene.
      Insertion of the element did not have an apparent effect on transcription
      initiation or chromatin structure. In nuclei isolated from anaerobically induced
      roots, in which Adh1 is transcriptionally active, a subset of the Adh1 chromatin
      is arranged in a unique conformation characterized by a generalized sensitivity
      to nucleases, specific DNAase I sensitive sites and a nucleosome array distinct
      from the inactive configuration present in leaf nuclei. The chromatin
      organization of the Mu1-induced mutant alleles is indistinguishable from that of
      the progenitor Adh1-S allele and a point mutant allele that is null for ADH1
      activity. The initiation of transcription also proved to be unaffected in these
      mutants. Nuclear runoff experiments indicated that Adh1 sequences upstream from
      the point of Mu1 insertion were transcribed normally, but sequences downstream to
      the insertion were drastically reduced relative to a reference gene expressed in
      anaerobic root nuclei. Thus, it was concluded that the defect in these Mu1
      induced mutants does not reside at the level of gene accessibility or transcript
      initiation. Rather, Mu1 presents an impediment to the progress of the polymerase
      II complex during transcript elongation. 

PMID- 24307423
TI  - Editorial.

PMID- 24307422
TI  - An analysis of tobacco mosaic virus replicative structures synthesized in vitro.
AB  - The RNA structures synthesized in vitro by a crude enzyme complex from tobacco
      mosaic virus (TMV)-infected leaves have been analyzed; the major viral-specific
      products were similar to TMV-replicative form (RF) and-replicative intermediate
      (RI) in electrophoretic behavior and ribonuclease sensitivity. Synthesis of these
      RF-like and RI-like structures neither required nor responded to added viral RNA,
      but did require all four ribonucleotide triphosphates. Enriched radiolabeled RF
      like and RI-like RNA fractions were isolated from non-denaturing agarose gels by
      electroelution and hybridized to a collection of TMV sequences cloned into
      bacteriophage M13. Enriched RF-RNA hybridized to sequences of both plus and minus
      polarity, while enriched RI-RNA hybridized only to inserts of minus polarity,
      indicating only plus strand synthesis in this fraction. Most of the label
      incorporated into the plus strand of the enriched RF-RNA was found near the 3'
      end of this strand, while most of the label incorporated into enriched RI-RNA was
      found several hundred bases from the 5'-end of the plus strand. 

PMID- 24307424
TI  - Cell tracking with caged xenon: using cryptophanes as MRI reporters upon cellular
      internalization.
AB  - Caged xenon has great potential in overcoming sensitivity limitations for
      solution-state NMR detection of dilute molecules. However, no application of such
      a system as a magnetic resonance imaging (MRI) contrast agent has yet been
      performed with live cells. We demonstrate MRI localization of cells labeled with
      caged xenon in a packed-bed bioreactor working under perfusion with
      hyperpolarized-xenon-saturated medium. Xenon hosts enable NMR/MRI experiments
      with switchable contrast and selectivity for cell-associated versus unbound
      cages. We present MR images with 10(3) -fold sensitivity enhancement for cell
      internalized, dual-mode (fluorescence/MRI) xenon hosts at low micromolar
      concentrations. Our results illustrate the capability of functionalized xenon to
      act as a highly sensitive cell tracer for MRI detection even without signal
      averaging. The method will bridge the challenging gap for translation to in vivo
      studies for the optimization of targeted biosensors and their multiplexing
      applications. 

PMID- 24307425
TI  - Body frame variation and adiposity in development, a mixed-longitudinal study of
      "Cape Coloured" children.
AB  - OBJECTIVES: The obesity epidemic is impacting both developed and undeveloped
      countries worldwide. It has only been recently that wide scale public campaigning
      has focused on prevention rather than intervention. Individual variations in food
      metabolism and energy expenditure may be responsible for much of the adiposity
      present amongst individuals. This article studies individual variation in
      relationship between lean trunk size and adiposity. METHODS: A mixed longitudinal
      growth study was conducted between 1986 and 1995 among urban and rural "Cape
      Coloured" schoolchildren from the Western Cape Province of South Africa. The
      sample consists of 127 females and 130 males between the ages of 6 and 20 years
      measured 6-9 times each. Correlations between age-standardized triceps,
      subscapular and abdominal skinfold thicknesses and quotient indices obtained by
      expressing trunk length, lower limb, and upper limb lengths and bi-acromial and
      bi-iliocristal diameters as percentages of body height were explored for each
      year of growth. RESULTS: Significant correlation coefficients (P < 0.05) between
      0.087 and 0.511 were found in both males and females, between bi-acromial and bi
      iliocristal indices and three skinfold thicknesses, but not between trunk and
      limb lengths and skinfolds. CONCLUSIONS: Skeletal frame width and amount of
      adiposity are correlated. The correlation persists longitudinally throughout
      childhood and adolescence in individuals living in very poor, as well as, in good
      environmental conditions.

PMID- 24307426
TI  - CT virtual cystourethroscopy for complex urethral strictures: an investigative,
      descriptive study.
AB  - PURPOSE: To compare the values of CT virtual cystourethroscopy and of
      conventional cystourethroscopy in diagnosing complex urethral strictures.
      METHODS: From January 2012 to December 2012, 33 patients, suspected of having
      complex urethral strictures before operation, were enrolled in this study. After
      CT scanning, a virtual cystourethroscopic view was software-generated.
      Conventional cystourethroscopy was also used before operation. The time durations
      of virtual cystourethroscopy and conventional cystourethroscopy were recorded.
      The accuracies of both techniques were compared using the actual findings from
      the operation. RESULTS: For 16 patients suffering from urethral strictures
      associated with various fistulas, the duration of examination with virtual
      cystourethroscopy was statistically significantly shorter than with conventional
      cystourethroscopy (P < 0.001). The detection rate of fistula by virtual
      cystourethroscopy was similar to than by conventional cystourethroscopy (P =
      0.057). The same results were obtained in eight patients suffering from urethral
      strictures associated with false passages. Only virtual cystourethroscopy could
      reveal the details of the urethral lumen in nine patients suffering from long
      anterior urethral strictures caused by lichen sclerosus. By contrast,
      conventional cystourethroscopy failed in those same patients. CONCLUSION: CT
      virtual cystourethroscopy is a useful technique for the diagnosis of urethral
      disease, especially in male patients suffering from complex urethral strictures.

PMID- 24307427
TI  - Association between hemoglobin, calcium, and lactate dehydrogenase variability
      and mortality among metastatic renal cell carcinoma.
AB  - PURPOSE: There are no robust data on hemoglobin (Hb), lactate dehydrogenase
      (LDH), and calcium variability for overall survival (OS) in patients with
      metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth
      factor (VEGF)-targeted therapy. We aim to evaluate prognostic implications of Hb,
      LDH, and calcium variability and establish a novel risk stratification model in
      RCC patients receiving targeted therapies. METHODS: We retrospectively studied an
      unselected cohort of patients with mRCC, who were treated with tyrosine kinase
      inhibitors. We assessed LDH variability, Ca variability, and Hb variability with
      various methods using standard deviation and fluctuation across thresholds.
      Kaplan-Meier and log-rank analyses were employed on OS and multivariate Cox
      proportional hazard model analyzed clinical parameters for their prognostic
      relevance. RESULTS: A total of 59 patients intermediate-risk group according to
      the Memorial Sloan-Kettering Cancer Center with mRCC who had early progressed
      after first-line therapy with interferon-alpha were included in this
      retrospective single-center study conducted between February 2008 and December
      2011. The mean Hb was 12.4 g/dl (min-max 9.1-15.2) throughout the study.
      Multivariable-adjusted Cox regression showed that patients in the consistently
      low-Hb group and patients in the low-amplitude and high-amplitude groups had a
      statistically significant increase in risk compared with patients who were
      consistently on target (HR 4.1; 95 % CI 1.3-12.9 and HR 2.9; 95 % CI 1.05-8.1 and
      HR 4.4; 95 % CI 1.7-11.1, respectively). On the other hand, the higher mean LDH
      (LDH more than 1 >upper limit of normal) was associated with OS. LDH variability
      and Ca variability were not associated with mortality. CONCLUSIONS: In patients
      with mRCC treated with VEGF-targeted therapy, Hb variability and mean LDH level
      might be associated with OS. This should be investigated prospectively.

PMID- 24307428
TI  - Left ventricular hypertrophy and chronic fluid overload in peritoneal dialysis
      patients.
AB  - PURPOSE: Cardiovascular disease is the leading cause of mortality in dialysis
      patients with left ventricular hypertrophy (LVH) being an important predictor of
      mortality. We wanted to determine the prevalence of LVH in peritoneal dialysis
      (PD) patients and factors contributing to it. METHODS: This is a cross-sectional
      study assessing LVH using echocardiogram in PD patients. Left ventricular mass
      index (LVMI) was calculated to determine LVH. Chronic fluid overload
      (overhydration) was assessed using the body composition monitor, and blood
      pressure (BP) was measured using 24-h ambulatory BP monitoring. RESULTS: Thirty
      one patients (21 females:10 males, 48.97 +/- 14.50 years and dialysis vintage
      40.0 +/- 28.9 months) were studied. More than two-thirds (77.4 %) were
      hypertensive, and a third (35.5 %) were diabetic. Baseline data included mean
      serum albumin (37.34 +/- 4.43 g/l), weekly Kt/V (2.02 +/- 0.23), residual renal
      function of 68 (0-880) ml and ultrafiltration of 1,606.9 +/- 548.6 ml. Majority
      of patients (80.6 %) had LVH on echocardiogram with LVMI of 136.5 +/- 37.8 g/m(2)
      and overhydration of 2.23 +/- 1.77 l. Average systolic BP, diastolic BP and mean
      arterial pressure were 141.2 +/- 23.3, 90.8 +/- 19.7 and 107.6 +/- 19.6 mmHg,
      respectively. Patients with LVH had a lower serum albumin (p = 0.003), were more
      overhydrated (p = 0.010) and were on higher number of anti-hypertensive agents (p
      <= 0.001). Predictors of LVMI were overhydration (p = 0.002), the presence of
      diabetes (p = 0.008) and the number of anti-hypertensive agents used (p = 0.026).
      However, overhydration (p = 0.007) was the main predictor of LVH on multivariate
      analysis. CONCLUSION: Overhydration is strongly associated with LVH in PD
      patients.

PMID- 24307429
TI  - Serum levels of fetuin-A, osteoprotegerin and osteopontin in patients with
      coronary artery disease: effects of statin (HMGCoA-reductase inhibitor) therapy.
AB  - BACKGROUND AND OBJECTIVES: Statins (HMGCoA-reductase inhibitors) produce numerous
      non-lipid related, 'pleiotropic' effects. Our aim was to investigate whether
      simvastatin treatment affects serum levels of vascular calcification inhibitors,
      such as fetuin-A, osteoprotegerin (OPG) and osteopontin (OPN), in patients with
      coronary artery disease (CAD). METHODS: A total of 98 statin-free patients with
      angiographically proven, newly diagnosed CAD were treated with simvastatin (20-40
      mg daily) for 6 months to target a low-density lipoprotein (LDL) level <100 mg/dL
      (the statin group [SG]). Thirty-five age- and sex-matched healthy individuals
      without any chronic metabolic or cardiovascular disease at baseline served as a
      healthy control group (HCG). Clinical, anthropometrical and metabolic parameters
      and serum fetuin-A, OPG, OPN and high-sensitivity C-reactive protein (hsCRP)
      levels were assayed at baseline in all participants and after 6 months only in SG
      patients. RESULTS: Compared with HCG subjects at baseline, SG patients exhibited
      higher serum levels of OPG (7.39 +/- 2.94 pmol/L vs 2.47 +/- 1.15 pmol/L, p <
      0.001), OPN (60.99 +/- 17.52 ng/mL vs 45.45 +/- 10.26 ng/mL, p = 0.005) and hsCRP
      (4.66 +/- 1.74 mg/L vs 1.58 +/- 0.56 mg/L, p < 0.001) as well as lower serum
      levels of fetuin-A (0.222 +/- 0.036 MUg/L vs 0.839 +/- 0.092 MUg/L, p < 0001).
      Apart from significantly reducing plasma total cholesterol and LDL, simvastatin
      also reduced serum levels of fetuin-A (by ~62.6 %), OPG (by ~47.2 %), OPN (by
      ~44.6 %) and hsCRP (by ~45.3 %) (p < 0.05) in SG patients. In standard multiple
      regression analysis, the simvastatin-induced reduction in fetuin-A was
      independently associated with changes in total cholesterol (beta = -0.289, p =
      0.048) and LDL (beta = -0.302, p = 0.032) (R (2) = 0.305, p = 0.040). CONCLUSION:
      Patients with CAD showed derangements in serum levels of all vascular
      calcification inhibitors compared with those in healthy controls. Simvastatin
      treatment for 6 months significantly decreased serum fetuin-A, OPG and OPN
      levels, but the clinical relevance of this requires further investigation.

PMID- 24307430
TI  - Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the
      maintenance of abstinence in alcohol dependence.
AB  - A liquid formulation of sodium oxybate (Alcover((r))), the sodium salt of gamma
      hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol
      withdrawal syndrome and for the maintenance of abstinence in alcohol dependence.
      This article reviews the efficacy and tolerability of sodium oxybate in alcohol
      withdrawal syndrome and in the maintenance of abstinence in alcohol dependence,
      as well as summarizing its pharmacological properties. Results of randomized
      controlled trials indicate that sodium oxybate was at least as effective as
      diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly
      alleviating symptoms, and was at least as effective as naltrexone or disulfiram
      in the maintenance of abstinence in alcohol-dependent patients. Sodium oxybate
      was generally well tolerated. The risk of sodium oxybate abuse is generally low
      when it is administered to alcohol-dependent patients at its approved dosage,
      under the supervision of a designated family member and with continuous strict
      medical surveillance. However, certain patient groups, such as patients with
      alcohol dependence and borderline personality disorder or who are in remission
      from heroin or cocaine addiction, may not be suitable candidates for sodium
      oxybate therapy because of an increased risk of abuse. In conclusion, sodium
      oxybate is a useful option for the treatment of alcohol withdrawal syndrome and
      for the maintenance of abstinence in alcohol dependence. 

PMID- 24307431
TI  - Tocilizumab monotherapy in a patient with rheumatoid arthritis and iatrogenic
      Kaposi sarcoma.
AB  - Kaposi sarcoma (KS) is a human herpesvirus-8-associated lymphoangioproliferative
      neoplasm. Both human and viral interleukin-6 (IL-6) proteins seem to drive much
      of the clinical manifestations of KS, which provides a new target for
      intervention by using IL-6-neutralizing antibodies. We describe the clinical
      course of a patient in whom tocilizumab, a monoclonal anti-IL-6 receptor antibody
      approved for rheumatoid arthritis (RA) treatment, was effective not only in
      inducing RA remission but was also safe for KS. 

PMID- 24307432
TI  - Nitrogen-doped porous graphitic carbon as an excellent electrode material for
      advanced supercapacitors.
AB  - An advanced supercapacitor material based on nitrogen-doped porous graphitic
      carbon (NPGC) with high a surface area was synthesized by means of a simple
      coordination-pyrolysis combination process, in which tetraethyl orthosilicate
      (TEOS), nickel nitrate, and glucose were adopted as porogent, graphitic catalyst
      precursor, and carbon source, respectively. In addition, melamine was selected as
      a nitrogen source owing to its nitrogen-enriched structure and the strong
      interaction between the amine groups and the glucose unit. A low-temperature
      treatment resulted in the formation of a NPGC precursor by combination of the
      catalytic precursor, hydrolyzed TEOS, and the melamine-glucose unit. Following
      pyrolysis and removal of the catalyst and porogent, the NPGC material showed
      excellent electrical conductivity owing to its high crystallinity, a large
      Brunauer-Emmett-Teller surface area (SBET =1027 m(2)  g(-1) ), and a high
      nitrogen level (7.72 wt %). The unusual microstructure of NPGC materials could
      provide electrochemical energy storage. The NPGC material, without the need for
      any conductive additives, showed excellent capacitive behavior (293 F g(-1) at 1
      A g(-1) ), long-term cycling stability, and high coulombic efficiency (>99.9 %
      over 5000 cycles) in KOH when used as an electrode. Notably, in a two-electrode
      symmetric supercapacitor, NPGC energy densities as high as 8.1 and 47.5 Wh kg(-1)
      , at a high power density (10.5 kW kg(-1) ), were achieved in 6 M KOH and 1 M Et4
      NBF4 -PC electrolytes, respectively. Thus, the synthesized NPGC material could be
      a highly promising electrode material for advanced supercapacitors and other
      conversion devices. 

PMID- 24307433
TI  - Biomimetic myocardial patches fabricated with poly(E-caprolactone) and
      polyethylene glycol-based polyurethanes.
AB  - The production of efficient heart patches for myocardium repair requires the use
      of biomaterials with high elastomeric properties and controllable
      biodegradability. To fulfil these design criteria we propose biodegradable
      poly(ester urethanes) and poly(ether ester urethanes) from poly(E-caprolactone)
      (PCL) and poly(ethylene glycol) (PEG) as macrodiols, 1,4-diisocyanatobutane as
      diisocyanate, l-Lysine Ethyl Ester and Alanine-Alanine-Lysine (AAK) as chain
      extenders. This peptide was used to tune biodegradability properties, since the
      Alanine-Alanine sequence is a target for the elastase enzyme. Enzymatic
      degradation tests demonstrated the feasibility of tuning biodegradability
      properties due to the introduction of AAK peptide in polyurethane backbone. Two
      formulations have been processed into porous scaffolds by Thermally-Induced Phase
      Separation (TIPS). Scanning Electron Microscopy micrographs revealed promising
      microstructures, which were characterized by stretched and unidirectional pores
      and mimicked the striated muscle tissue. Tensile tests showed that, although
      scaffolds are characterized by lower mechanical properties than films, these
      substrates have suitable elastomeric behaviors and elastic moduli for contractile
      and soft tissue regeneration. Viability tests on cardiomyocytes revealed the best
      cell response for dense film and porous scaffold obtained from PCL and Lysine
      Ethyl Ester-based polyurethane, with an increased viability for the porous
      substrate, which is ascribable to the morphological features of its
      microstructure. Future works will be addressed to study the in vivo behavior of
      these constructs and to confirm their applicability for myocardial tissue
      engineering.

PMID- 24307434
TI  - Hiatal hernia repair in laparoscopic adjustable gastric banding and laparoscopic
      Roux-en-Y gastric bypass: a national database analysis.
AB  - Hiatal hernia (HH) repairs are commonly done concomitantly with laparoscopic Roux
      en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB) to
      decrease gastroesophageal reflux disease (GERD). There is limited evidence about
      the additional surgical risk these combined procedures engender. We used the
      United States Nationwide Inpatient Sample 2004-2009 to compare mortality risk,
      prolonged length of stay (PLOS), and perioperative adverse events using
      propensity score-matched analysis. We repeated the analysis after removing
      patients diagnosed with GERD. There were 42,272 weighted patients undergoing
      LRYGB alone representing 206,559 discharges nationally and an additional 1,945
      and 9,060, respectively, undergoing LRYGB + HH repair. For LAGB, there were
      10,558 records representing 52,901 LAGB-only discharges and 1,959 representing
      9,893 LAGB + HH repair discharges. Thirty-eight percent (95 % CI: 36, 41 %) of
      the patients in the LRYGB-only group had GERD compared to 55 % (51, 59 %) in the
      LRYGB + HH repair group. Among the LAGB groups, 31 % (28, 34 %) of LAGB-only
      patients had GERD compared to 44 % (38, 49 %) in the LAGB + HH repair group. We
      find that the average treatment effect on the treated (considering the
      concomitant procedure as treatment and the single procedure as control) for PLOS
      was -0.12353 (-0.15909, -0.08797) between the LRYGB groups and -0.04353 (
      0.07488, -0.01217) for the LAGB groups. We find no evidence of increased risk of
      perioperative adverse events among patients undergoing concomitant HH repair with
      LRYGB or LAGB. Patients undergoing the combined procedure appear to be at lower
      risk of PLOS; this may be due to surgical training norms.

PMID- 24307435
TI  - Bariatric surgery may improve employment status in unemployed, underserved,
      severely obese patients.
AB  - BACKGROUND: The purpose of this study was to determine the impact of bariatric
      surgery on employment status in underserved, unemployed patients with severe
      obesity. METHODS: A retrospective review of all unemployed severely obese
      patients seen in our urban safety-net bariatric surgery program was performed.
      Preoperative patient questionnaires and medical records were reviewed to evaluate
      patient employment status at the time of initial evaluation by the
      multidisciplinary bariatric surgery team. Follow-up data was obtained on all
      available patients (including those who did not undergo surgery), including
      weight and employment status. A standardized telephone questionnaire was
      administered to supplement details regarding employment. Changes in employment
      status and body weight were determined in both groups. RESULTS: Here, 193
      unemployed severely obese patients were evaluated by the multidisciplinary
      obesity team. The vast majority of patients (>80%) were minorities (primarily
      Hispanic) and publicly insured. Seventy-two underwent bariatric surgery and 121
      did not. Twenty-four percent of the surgical patients and 9% of the non-surgical
      patients had acquired full-time employment at least one year postoperatively (p =
      0.043). There was a 10-point body mass index reduction in the surgical group,
      compared to 1-point reduction in the non-surgical group after one year.
      CONCLUSIONS: Bariatric surgery may improve employment status in an unemployed
      severely obese patient cohort. Future research in this area should collect
      detailed prospective data on employment prior to surgery and assess changes
      longitudinally to provide a more complete picture of the impact of bariatric
      surgery on employment.

PMID- 24307437
TI  - Peritoneal dialysis: a Cinderella that must become a Princess.

PMID- 24307436
TI  - Laparoscopic greater curvature plication in morbidly obese women with type 2
      diabetes: effects on glucose homeostasis, postprandial triglyceridemia and
      selected gut hormones.
AB  - BACKGROUND: Laparoscopic greater curvature plication (LGCP) is an emerging
      bariatric procedure that reduces the gastric volume without implantable devices
      or gastrectomy. The aim of this study was to explore changes in glucose
      homeostasis, postprandial triglyceridemia, and meal-stimulated secretion of
      selected gut hormones [glucose-dependent insulinotropic polypeptide (GIP),
      glucagon-like peptide-1 (GLP-1), ghrelin, and obestatin] in patients with type 2
      diabetes mellitus (T2DM) at 1 and 6 months after the procedure. METHODS: Thirteen
      morbidly obese T2DM women (mean age, 53.2 +/- 8.76 years; body mass index, 40.1
      +/- 4.59 kg/m2) were prospectively investigated before the LGCP and at 1- and 6
      month follow-up. At these time points, all study patients underwent a
      standardized liquid mixed-meal test, and blood was sampled for assessment of
      plasma levels of glucose, insulin, C-peptide, triglycerides, GIP, GLP-1, ghrelin,
      and obestatin. RESULTS: All patients had significant weight loss both at 1 and 6
      months after the LGCP (p <= 0.002), with mean percent excess weight loss (%EWL)
      reaching 29.7 +/- 2.9% at the 6-month follow-up. Fasting hyperglycemia and
      hyperinsulinemia improved significantly at 6 months after the LGCP (p < 0.05),
      with parallel improvement in insulin sensitivity and HbA1c levels (p < 0.0001).
      Meal-induced glucose plasma levels were significantly lower at 6 months after the
      LGCP (p < 0.0001), and postprandial triglyceridemia was also ameliorated at the 6
      month follow-up (p < 0.001). Postprandial GIP plasma levels were significantly
      increased both at 1 and 6 months after the LGCP (p < 0.0001), whereas the overall
      meal-induced GLP-1 response was not significantly changed after the procedure (p
      > 0.05). Postprandial ghrelin plasma levels decreased at 1 and 6 months after the
      LGCP (p < 0.0001) with no significant changes in circulating obestatin levels.
      CONCLUSION: During the initial 6-month postoperative period, LGCP induces
      significant weight loss and improves the metabolic profile of morbidly obese T2DM
      patients, while it also decreases circulating postprandial ghrelin levels and
      increases the meal-induced GIP response.

PMID- 24307438
TI  - Guidelines of the Peritoneal Dialysis Study Group of the Italian Society of
      Nephrology.

PMID- 24307440
TI  - Clinical effects of biocompatible dialysis fluids.

PMID- 24307439
TI  - The peritoneal dialysis catheter.
AB  - The results obtained from the positioning and management of the catheter for
      peritoneal dialysis depend on the techniques used, but also and above all, on the
      experience of the practitioners. A comparison between practitioners may help to
      change their convictions, as well as to further improve results, in the interests
      of patient welfare. This is the aim of these Best Practice Guidelines.. 

PMID- 24307441
TI  - Prescription in peritoneal dialysis.

PMID- 24307442
TI  - Dialysis adequacy in peritoneal dialysis.

PMID- 24307443
TI  - Functional assessment of the peritoneal membrane.

PMID- 24307444
TI  - A comparison between continuous ambulatory and automated peritoneal.

PMID- 24307445
TI  - Peritoneal ultrafiltration in patients with advanced decompensated heart failure.
AB  - The aim of the Best Practice guidelines on peritoneal ultrafiltration (UF) in
      patients with treatment-resistant advanced decompensated heart failure (TR-AHDF)
      is to achieve a common approach to the management of decompensated heart failure
      in those situations in which all conventional treatment options have been
      unsuccessful, and to stimulate a closer cooperation between nephrologists and
      cardiologists. The standardization of the case series of different centers would
      allow a better definition of the results published in the literature, without
      which they are nothing more than anecdotes. TR-AHDF is characterized by the
      persistence of severe symptoms even when all possible pharmacological and
      surgical options have been exhausted. These patients are often treated with
      methods that allow extracorporeal UF - slow continuous ultrafiltration (SCUF) and
      continuous renal replacement therapy (CRRT) - which have to be performed in
      hospital facilities. Peritoneal ultrafiltration (PUF) can be considered a
      treatment option in patients with TR-AHDF when, despite the fact that all
      treatment options have been used, patients meet the following criteria: * stage D
      decompensated heart failure (ACC/AHA classification); * INTERMACS level 4
      decompensated heart failure; * INTERMACS frequent flyer profile; * chronic renal
      failure (estimated glomerular filtration rate <50 ml/min per 1.73 m2: KDOQI
      classification stage 3 chronic kidney disease); * no obvious contraindications to
      peritoneal UF. PUF treatment modes are derived from the treatment regimens
      proposed by various authors to obtain systemic UF in patients with severe
      decompensated heart failure, using manual and automated incremental peritoneal
      dialysis involving various glucose concentrations in addition to the single
      icodextrin exchange. These guidelines also identify a minimum set of tests and
      procedures for the follow-up phase, to be supplemented, according to the center's
      resources and policy, with other tests that are less routine or more complex also
      from a logistic/organizational standpoint, emphasizing the need for the patient's
      clinical and treatment program to involve both the nephrologist and the
      cardiologist. The pathophysiological aspects of a deterioration in kidney
      function in patients with decompensated heart failure are also considered, and
      the results of PUF in patients with decompensated heart failure reported in the
      various case series are reviewed. 

PMID- 24307446
TI  - Encapsulating peritoneal sclerosis.
AB  - The purpose of this best practice is to briefly define what has now been accepted
      regarding encapsulating peritoneal sclerosis (EPS), highlighting the latest
      developments and outlining future lines of research. The medical therapy that can
      be proposed (to be discussed individually, verifying the individual features of
      the patient) appears to include steroids, tamoxifen, and sirolimus or everolimus,
      with blood levels maintained at reference values for post-transplantation
      therapy. In view of the high incidence of relapse also in responders, it appears
      appropriate to continue therapy for prolonged periods, at least for 6 months.
      Moreover, a surgical assessment is indicated, especially for patients with
      intestinal symptoms including subocclusion status. To date the prevention of EPS
      is an unresolved issue. The recommended measures include the accurate prevention
      and best treatment of acute peritonitis, the use of biocompatible dialysis fluids
      (there is no consensus on their exact definition) and the monitoring of
      ultrafiltration characteristics and peritoneal membrane transport. Other
      recommended measures are the extensive use of renin-angiotensin- aldosterone axis
      inhibitors for the treatment of arterial hypertension in PD and the exclusion of
      beta- blockers. Other suggested strategies are tamoxifen prophylaxis in cases at
      risk and to adopt personalized immunosuppressive protocols for patients with PD
      who undergo renal transplantation. 

PMID- 24307447
TI  - Primate sociality to human cooperation. Why us and not them?
AB  - Developmental psychologists identify propensities for social engagement in human
      infants that are less evident in other apes; Sarah Hrdy links these social
      propensities to novel features of human childrearing. Unlike other ape mothers,
      humans can bear a new baby before the previous child is independent because they
      have help. This help alters maternal trade-offs and so imposes new selection
      pressures on infants and young children to actively engage their caretakers'
      attention and commitment. Such distinctive childrearing is part of our
      grandmothering life history. While consequences for other cooperative activities
      must surely follow, the novel rearing environments set up by helpful
      grandmothering can explain why natural selection escalated preferences and
      motivations for interactivity in our lineage in the first place, and why, unlike
      other aspects of infant development, social sensitivities are not delayed in
      humans compared with genus Pan. 

PMID- 24307449
TI  - LCIB in the Chlamydomonas CO2-concentrating mechanism.
AB  - The CO2-concentrating mechanism confers microalgae a versatile and efficient
      strategy for adapting to a wide range of environmental CO2 concentrations. LCIB,
      which has been demonstrated as a key player in the eukaryotic algal CO2
      concentrating mechanism (CCM), is a novel protein in Chlamydomonas lacking any
      recognizable domain or motif, and its exact function in the CCM has not been
      clearly defined. The unique air-dier growth phenotype and photosynthetic
      characteristics in the LCIB mutants, and re-localization of LCIB between
      different subcellular locations in response to different levels of CO2, have
      indicated that the function of LCIB is closely associated with a distinct low CO2
      acclimation state. Here, we review physiological and molecular evidence linking
      LCIB with inorganic carbon accumulation in the CCM and discuss the proposed
      function of LCIB in several inorganic carbon uptake/accumulation pathways.
      Several new molecular characteristics of LCIB also are presented. 

PMID- 24307451
TI  - Physiological stratification in electricity-producing biofilms of Geobacter
      sulfurreducens.
AB  - The elucidation of mechanisms and limitations in electrode respiration by
      electroactive biofilms is significant for the development of rapidly emerging
      clean energy production and wastewater treatment technologies. In Geobacter
      sulfurreducens biofilms, the controlling steps in current production are thought
      to be the metabolic activity of cells, but still remain to be determined. By
      quantifying the DNA, RNA, and protein content during the long-term growth of
      biofilms on polarized graphite electrodes, we show in this work that current
      production becomes independent of DNA accumulation immediately after a maximal
      current is achieved. Indeed, the mean respiratory rate of biofilms rapidly
      decreases after this point, which indicates the progressive accumulation of cells
      that do not contribute to current production or contribute to a negligible
      extent. These results support the occurrence of physiological stratification
      within biofilms as a consequence of respiratory limitations imposed by limited
      biofilm conductivity. 

PMID- 24307448
TI  - The insectan apes.
AB  - I present evidence that humans have evolved convergently to social insects with
      regard to a large suite of social, ecological, and reproductive phenotypes.
      Convergences between humans and social insects include: (1) groups with
      genetically and environmentally defined structures; (2) extensive divisions of
      labor; (3) specialization of a relatively restricted set of females for
      reproduction, with enhanced fertility; (4) extensive extramaternal care; (5)
      within-group food sharing; (6) generalized diets composed of high-nutrient
      density food; (7) solicitous juveniles, but high rates of infanticide; (8)
      ecological dominance; (9) enhanced colonizing abilities; and (10) collective,
      cooperative decision-making. Most of these convergent phenotypic adaptations stem
      from reorganization of key life-history trade-offs due to behavioral,
      physiological, and life-historical specializations. Despite their extensive
      socioreproductive overlap with social insects, humans differ with regard to the
      central aspect of eusociality: reproductive division of labor. This difference
      may be underpinned by the high energetic costs of producing offspring with large
      brains. 

PMID- 24307453
TI  - Thyrolinguofacial trunk arising from the carotid bifurcation determined by
      cadaver dissection.
AB  - Knowledge of the arterial variations in the neck region may be of great
      importance in the diagnosis and treatment of cervical and maxillofacial
      pathologies. We report on a male cadaver found to have a superior thyroid,
      lingual and facial artery arising with a common trunk from the relatively high
      carotid bifurcation on the right side. After branching off the superior thyroid
      artery, the linguofacial trunk divided in the submandibular region into the
      lingual and the facial artery. The embryogenesis of such a combination of
      anomalies is not clear, but the anatomic consequences may have important clinical
      implications for radiologic examinations and surgical procedures in the regions
      of the head and neck. 

PMID- 24307452
TI  - Comparison of D-dimer point of care test (POCT) against current laboratory test
      in patients with suspected venous thromboembolism (VTE) presenting to the
      emergency department (ED).
AB  - AIMS: To compare quantitative point of care (POC) with laboratory d-dimer testing
      in patients with suspected venous thromboembolism (VTE) presenting to the
      emergency department. METHODS: A prospective single centre diagnostic study in
      adults presenting with suspected VTE (pleuritic chest pain or leg swelling)
      RESULTS: Main outcome measures were the statistical correlation of the two
      methods. Secondary outcome measures were: test turnaround times, correlation
      between D-dimer levels, Wells score and final diagnosis. The results showed that
      there was strong evidence of POC D-dimer being sufficiently accurate to be used
      as a screening device. The correlation between the two logged assay scores was
      good. Both logged scores correlated similarly with the Wells score. Once an
      equivalent cut-off value for POC D-dimer (412 ng/mL) was established, there were
      only 4 of 100 cases all of which were extremely close to the cut-off. D-dimer
      turnaround time decreased by 83%. A further recent analysis of laboratory times
      done in 2013 demonstrates that POC D-dimer results remain 62% quicker. Based on
      the D-dimer results 27 patients were scanned. The median Wells score in this
      group was 3.0 (range 2-10) median POC D-dimer levels of 2590 (412-5000) and
      median lab D-dimer levels of 864 (230-13 000) showing good correlation between D
      dimer positive patients and the Wells score. Seven patients had positive scans.
      There was a significant difference in both logged D-dimer scores between the
      negative and positive groups indicating that raised D-dimer levels correlate well
      with final diagnosis. CONCLUSIONS: The POC device was comparable with the
      laboratory device and was sufficiently accurate to be used as a screening tool in
      the emergency department setting.

PMID- 24307454
TI  - Lyotropic lamellar phase formed from monolayered theta-shaped carborane-cage
      amphiphiles.

PMID- 24307455
TI  - Labeled oxazaphosphorines for applications in mass spectrometry studies. 2.
      Synthesis of deuterium-labeled 2-dechloroethylcyclophosphamides and 2- and 3
      dechloroethylifosfamides.
AB  - The prodrugs cyclophosphamide (CP) and ifosfamide (IF) each metabolize to an
      active alkylating agent through a cytochrome P450-mediated oxidation at the C-4
      position. Competing with this activation pathway are enzymatic oxidations at the
      exocyclic alpha and alpha' carbons, which result in dechloroethylation of CP and
      IF. The incidence of oxidation at one position relative to another is believed to
      be at least one factor underlying the high degree of interpatient variability in
      both CP and IF pharmacokinetics. As standards for the mass spectrometry
      quantification of dechloroethylation, the following were synthesized: (1)
      [4,4,5,5-(2) H4 ]-2-dechloroethylcyclophosphamide (equivalent to [4,4,5,5-(2) H4
      ]-3-dechloroethylifosfamide); (2) [alpha,alpha,4,4,5,5-(2) H6 ]-2
      dechloroethylcyclophosphamide (equivalent to [alpha,alpha,4,4,5,5-(2) H6 ]-3
      dechloroethylifosfamide); and (3) [alpha,alpha,4,4,5,5-(2) H6 ]-2
      dechloroethylifosfamide. The common precursor to all of the target compounds was
      [2,2,3,3-(2) H4 ]-3-aminopropanol. A one-pot reaction of this compound with POCl3
      and unlabeled or labeled 2-chloroethylamine hydrochloride gave the d4 and d6
      labeled 2-dechloroethylcyclophosphamides. The construction of the 2
      dechloroethylifosfamide from the aminopropanol required five discreet steps.
      Optimization of the synthetic pathways and stability studies are discussed. 

PMID- 24307457
TI  - Growth factors expression in hyaluronic acid fat graft myringoplasty.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the effect of hyaluronic acid (HA)
      associated to fat graft on growth factors expression during the healing process
      of tympanic membrane (TM) perforations in guinea pigs using the hyaluronic acid
      fat graft myringoplasty (HAFGM) technique. STUDY DESIGN: Prospective randomized
      animal study. METHODS: Thirty guinea pigs were divided equally into three groups:
      group I (control group), group II (fat graft myringoplasty technique), and group
      III (HAFGM technique). TMs were perforated on day 1 and then sampled on days 0,
      3, 8, and 21 and tested for the expression of: epidermal growth factor (EGF),
      insulin-like growth factor (IGF), tumor necrosis factor alpha (TNF alpha),
      vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF).
      Five perforated TMs were taken at day 0 from group I to serve as a reference
      level. RESULTS: Group III showed an increased expression of all tested growth
      factors, except for KGF. EGF was highest in the early healing process; then IGF
      peaked at day 8 with statistically significant increase compared to groups I and
      II. TNF alpha in group III was significantly higher than group I throughout the
      study, with a peak level at day 21. VEGF was significantly higher in group III
      compared to group I at days 3 and 21. Neovascularization and scarless TM closure
      was obtained in group III, while spontaneous closure was associated with thin
      layered and scarred TM in group I. CONCLUSIONS: HA association to fat graft in
      perforated TM increases the expression of the endogenous growth factors,
      suggesting that such an association is advantageous for healing. LEVEL OF
      EVIDENCE: N/A.

PMID- 24307456
TI  - On the cutting edge of organ renewal: Identification, regulation, and evolution
      of incisor stem cells.
AB  - The rodent incisor is one of a number of organs that grow continuously throughout
      the life of an animal. Continuous growth of the incisor arose as an evolutionary
      adaptation to compensate for abrasion at the distal end of the tooth. The
      sustained turnover of cells that deposit the mineralized dental tissues is made
      possible by epithelial and mesenchymal stem cells residing at the proximal end of
      the incisor. A complex network of signaling pathways and transcription factors
      regulates the formation, maintenance, and differentiation of these stem cells
      during development and throughout adulthood. Research over the past 15 years has
      led to significant progress in our understanding of this network, which includes
      FGF, BMP, Notch, and Hh signaling, as well as cell adhesion molecules and micro
      RNAs. This review surveys key historical experiments that laid the foundation of
      the field and discusses more recent findings that definitively identified the
      stem cell population, elucidated the regulatory network, and demonstrated
      possible genetic mechanisms for the evolution of continuously growing teeth.

PMID- 24307458
TI  - Effect of carotenoid beta-cryptoxanthin on cellular and humoral immune response
      in rabbit.
AB  - Beta-cryptoxanthin (b-Cr) is a pro-vitamin A and one of the major carotenoids
      that can be commonly found in mammalian serum and tissues. Foods rich in certain
      fatty acids are known to be effective to gain a healthy immune system. In the
      present study, we evaluated the effect of b-Cr on rabbit humoral and cellular
      immune responses to have a better vision about the mechanism of effect of
      carotenoids on immune system. Twenty rabbits were randomly divided into five
      groups (4 per group): Groups consisted of: 1) control group (normal saline; 2) b
      Cr (control); 3) vaccine control; 4) 5 mg/kg b-Cr o.p. + vaccine; 5) 10 mg/kg b
      Cr o.p. + vaccine. Blood samples were obtained from the marginal ear artery at
      three time points: days 0, 14 and 21 of the study. Blood CD4+ and CD8+
      lymphocytes and Serum Immunoglobulin and Cytokines content were evaluated.
      Results show that b-Cr administration increased the blood CD4+ lymphocytes count
      (P > 0.01). Serum IgG, IgM and IgA levels increased (P > 0.05) following b-Cr
      administration. b-Cr treatment increased serum IL-4 levels (P > 0.05). According
      to presented results, b-Cr may increase the humoral immunity in mammals. So, it
      would possible has a potentially beneficial effect on health and on prevention of
      the immunity related diseases. 

PMID- 24307459
TI  - Optimization of immune strategy for a construct of Salmonella-delivered ApxIA,
      ApxIIA, ApxIIIA and OmpA antigens of Actinobacillus pleuropneumoniae for
      prevention of porcine pleuropneumonia using a murine model.
AB  - In this study, the Actinobacillus pleuropneumoniae antigens ApxIA, ApxIIA,
      ApxIIIA and OmpA were expressed in an attenuated strain of Salmonella
      (?lon?cpxR?asd) for prevention of porcine pleuropneumonia. In order to evaluate
      the immunization strategy of the construct, a total 60 BALB/c mice were equally
      divided into four groups (n = 15). Group A mice were intranasally immunized only
      at 6-weeks-of-age, while group B mice were intransally primed and boosted at 6-
      and 9-weeks-of-age, respectively, and group C mice were intransally primed at 6
      weeks-of-age and subsequently boosted twice at 9- and 12-weeks-of-age. Group D
      mice were used as a control, which were inoculated with sterile PBS. Groups A, B,
      and C showed significantly higher serum IgG and fecal IgA immune responses than
      those of the control group. After virulent challenge with a wild type A.
      pleuropneumoniae, the immunized groups A, B and C showed 33.3 %, 13.3 % and 26.7
      % mortality as the control group showed 60 % mortality. These results showed that
      the protection against porcine pleuropneumonia using the construct can be
      optimized by a double intranasal vaccination.

PMID- 24307460
TI  - Antiviral interventions for liver transplant patients with recurrent graft
      infection due to hepatitis C virus.
AB  - BACKGROUND: Antiviral therapy for recurrent hepatitis C infection after liver
      transplantation is controversial due to unresolved balance between benefits and
      harms. OBJECTIVES: To compare the therapeutic benefits and harms of different
      antiviral regimens in patients with hepatitis C re-infected grafts after liver
      transplantation. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation
      Index Expanded to February 2013. SELECTION CRITERIA: We considered only
      randomised clinical trials (irrespective of language, blinding, or publication
      status) comparing various antiviral therapies (alone or in combination) in the
      treatment of hepatitis C virus recurrence in liver transplantation for the
      review. DATA COLLECTION AND ANALYSIS: Two authors collected the data
      independently. We calculated the risk ratio (RR) or mean difference (MD) with 95%
      confidence intervals (CI) using the fixed-effect and the random-effects models
      based on available case-analysis. In the presence of only trials for a
      dichotomous outcome, we performed the Fisher's exact test. MAIN RESULTS: Overall,
      17 trials with 736 patients met the inclusion criteria for this review. All
      trials had high risk of bias. Five hundred and one patients randomised in 11
      trials provided information for various comparisons in this systematic review
      after excluding post-randomisation drop-outs and patients from trials that did
      not report any of the outcomes of interest for this review. The comparisons for
      which outcomes were available included pegylated (peg) interferon versus control;
      peg interferon plus ribavirin versus control; ribavirin plus peg interferon
      versus peg interferon; peg interferon (1.5 MUg/kg/week) plus ribavirin versus peg
      interferon (0.5 MUg/kg/week) plus ribavirin; amantadine plus peg interferon plus
      ribavirin versus peg interferon plus ribavirin; interferon versus control;
      interferon plus ribavirin versus control; ribavirin versus interferon; and
      ribavirin versus placebo. Long-term follow-up was not available in these trials.
      There were no significant differences in mortality, retransplantation, graft
      rejections requiring retransplantation or medical treatment, or fibrosis
      worsening between the groups in any of the comparisons in which these outcomes
      were reported. Quality of life and liver decompensation were not reported in any
      of the trials. There was a significantly higher proportion of participants who
      developed serious adverse events in the ribavirin plus peg interferon combination
      therapy group than in the peg interferon monotherapy group (1 trial; 56
      participants; 17/28 (60.7%) in the intervention group versus 5/28 (17.9%) in the
      control group; RR 3.40; 95% CI 1.46 to 7.94). There was no significant difference
      in proportion of participants who developed serious adverse events or in the
      number of serious adverse events between the intervention and control groups in
      the other comparisons that reported serious adverse events. AUTHORS' CONCLUSIONS:
      Considering the lack of clinical benefit, there is currently no evidence to
      recommend or refute antiviral treatment for recurrent liver graft infection with
      hepatitis C virus. Further randomised clinical trials with low risk of bias and
      low risk of random errors with adequate duration of follow-up are necessary.

PMID- 24307461
TI  - Exploring self-criticism: confirmatory factor analysis of the FSCRS in clinical
      and nonclinical samples.
AB  - The Forms of Self-criticizing/Attacking and Self-reassuring Scale (FSCRS) is a
      self-report questionnaire that assesses the forms of self-criticism and self
      reassurance. The aim of this study was to explore the latent structure of the
      FSCRS in nonclinical and clinical samples. Data from 381 participants from the
      general population and from 304 participants from clinical settings were
      subjected to confirmatory factor analyses to explore several structural models
      reflecting alternative representations of the FSCRS dimensionality. Overall, the
      model with the best fit to the data, in both samples, was the three-factor model
      (inadequate self, hated self and reassured self subscales) replicating the FSCRS
      original structure. The scale showed good psychometric characteristics, and the
      three factors discriminated between the clinical and nonclinical samples. To our
      knowledge, this is the first study to confirm the factor structure of the FSCRS
      in a purely clinical sample, and to test alternative models. This study adds to
      the existent literature that has been supporting the conceptualization of self
      criticism as a multidimensional construct. Given the good psychometric properties
      of the Portuguese version of the FSCRS, its use is encouraged and recommended for
      the assessment of self-criticism in both clinical and research settings.

PMID- 24307462
TI  - Hole burning study of excited state structure and energy transfer dynamics of
      bacteriochlorophyll c in chlorosomes of green sulphur photosynthetic bacteria.
AB  - Results of low temperature fluorescence and spectral hole burning experiments
      with whole cells and isolated chlorosomes of the green sulfur bacterium
      Chlorobium limicola containing BChl c are reported. At least two spectral forms
      of BChl c (short-wavelength and long-wavelength absorbing BChl c) were identified
      in the second derivative fluorescence spectra. The widths of persistent holes
      burned in the fluorescence spectrum of BChl c are determined by excited state
      lifetimes due to fast energy transfer. Different excited state lifetimes for both
      BChl c forms were observed. A site distribution function of the lowest excited
      state of chlorosomal BChl c was revealed. The excited state lifetimes are
      strongly influenced by redox conditions of the solution. At anaerobic conditions
      the lifetime of 5.3 ps corresponds to the rate of energy transfer between BChl c
      clusters. This time shortens to 2.6 ps at aerobic conditions. The shortening may
      be caused by introducing a quencher. Spectral bands observed in the fluorescence
      of isolated chlorosomes were attributed to monomeric and lower state aggregates
      of BChl c. These forms are not functionally connected with the chlorosome. 

PMID- 24307463
TI  - Exciton states of the antenna and energy trapping by the reaction center.
AB  - Forward and back energy transfer between antenna and RC in the photosynthetic
      apparatus of purple bacteria was studied taking into account the exciton states
      of the antenna. The exciton states were calculated for core antenna configuration
      in the form of a circular aggregate of N identical BChl molecules with the CN
      symmetry. The influence of pigment inhomogeneity on the proposed exciton
      description of the antenna and its interaction with RC was investigated. The
      ratio between the rate constants of forward and back energy transfer between the
      exciton levels of the antenna and RC was obtained as a function of the
      temperature, the number of antenna BChls and the antenna exciton level position
      with respect to BChl special pair level of RC. A versatile analytical expression
      for this ratio which is independent of the BChl special pair level position and
      its dipole orientation was derived. The proposed model results in an irreversible
      excitation trapping by RC even at room temperature. 

PMID- 24307464
TI  - The consequences of chlorophyll deficiency for photosynthetic light use
      efficiency in a single nuclear gene mutation of cowpea.
AB  - The light harvesting and photosynthetic characteristics of a chlorophyll
      deficient mutant of cowpea (Vigna unguilata), resulting from a single nuclear
      gene mutation, are examined. The 40% reduction in total chlorophyll content per
      leaf area in the mutant is associated with a 55% reduction in pigment-proteins of
      the light harvesting complex associated with Photosystem II (LHC II), and to a
      lesser extent (35%) in the light harvesting complex associated with Photosystem I
      (LHC I). No significant differences were found in the Photosystem I (PS I) and
      Photosystem II (PS II) contents per leaf area of the mutant compared to the
      wildtype parent. The decreases in the PS I and PS II antennae sizes in the mutant
      were not accompanied by any major changes in quantum efficiencies of PS I and PS
      II in leaves at non-saturating light levels for CO2 assimilation. Although the
      chlorophyll deficiency resulted in an 11% decrease in light absorption by mutant
      leaves, their maximum quantum yield and light saturated rate of CO2 assimilation
      were similar to those of wildtype leaves. Consequently, the large and different
      decreases in the antennae of PS II and PS I in the mutant are not associated with
      any loss of light use efficiency in photosynthesis. 

PMID- 24307465
TI  - Photoinduced formation of pheophytin/chlorophyll-containing complexes during the
      greening of plant leaves.
AB  - Illumination of etiolated maize leaves with low-intensity light produces a
      chlorophyll/pheophytin-containing complex. The complex contains two native
      chlorophyll forms Chl 671/668 and Chl 675/668 as well as pheophytin Pheo 679/675
      (with chlorophyll/pheophytin ratio of 2/1). The complex is formed in the course
      of two successive reactions: reaction of protochlorophyllide Pchlde 655/650
      photoreduction resulted in chlorophyllide Chlde 684/676 formation, and the
      subsequent dark reaction of Chlde 684/676 involving Mg substitution by H2 in
      pigment chromophore and pigment esterification by phytol. Out data show that the
      reaction leading to chlorophyll/pheophytin-containing complex formation is not
      destructive. The reaction is in fact biosynthetic, and is competitive with the
      known reactions of biosynthesis of the bulk of chlorophyll molecules. The
      relationship between chlorophyll and pheophytin biosynthesis reactions is
      controlled by temperature, light intensity and exposure duration.The native
      complex containing pheophytin a and chlorophyll a is supposed to be a direct
      precursor of the PS II reaction centre in plant leaves. 

PMID- 24307466
TI  - Selective extraction of CP 26 and CP 29 proteins without affecting the binding of
      the extrinsic proteins (33, 23 and 17 kDa) and the DCMU sensitivity of a
      Photosystem II core complex.
AB  - A highly purified oxygen evolving Photosystem II core complex was isolated from
      PS II membranes solubilized with the non-ionic detergent n-octyl-beta-D
      thioglucoside. The three extrinsic proteins (33, 23 and 17 kDa) were functionally
      bound to the PS II core complex. Selective extraction of the 22, 10 kDa, CP 26
      and CP 29 proteins demonstrated that these species are not involved in the
      binding of the extrinsic proteins (33, 23 and 17 kDa) or the DCMU sensitivity of
      the Photosystem II complex. 

PMID- 24307467
TI  - Deletion of cytochrome c oxidase genes from the cyanobacterium Synechocystis sp.
      PCC6803: Evidence for alternative respiratory pathways.
AB  - An oligonucleotide directed against a highly conserved region of aa3-type
      cytochrome c oxidases was used to clone the cox genes from the cyanobacterium
      Synechocystis sp. PCC6803. Several overlapping clones were obtained that
      contained the coxB, coxA, and coxC genes, transcribed in the same direction in
      that order, coding for subunits II, I, and III, respectively. The deduced protein
      sequences of the three subunits showed high sequence similarity with the
      corresponding subunits of all known aa3-type cytochrome c oxidases. A 1.94-kb
      HindII fragment containing most of coxA and about half of coxC was deleted and
      replaced by a cassette coding for kanamycin resistance. Mutant cells that were
      homozygous for the deleted cox locus were obtained. They were viable under
      photoautotrophic and photoheterotrophic conditions, but contained no cytochrome c
      oxidase activity. Nevertheless, these mutant cells showed almost normal
      respiration, defined as cyanide-inhibitable O2 uptake by whole cells in the dark.
      It is concluded, therefore, that aa3-type cytochrome c oxidase is not the only
      terminal respiratory oxidase in Synechocystis sp. PCC6803. 

PMID- 24307468
TI  - Inhibition of PS II photochemistry by PAR and UV radiation in natural
      phytoplankton communities.
AB  - The effects of PAR and UV radiation on PS II photochemistry were examined in
      natural phytoplankton communities from coastal waters off Rhode Island (USA) and
      the subtropical Pacific. The photochemical energy conversion efficiency, the
      functional absorption cross section and the kinetics of electron transfer on the
      acceptor side of PS II were derived from variable fluorescence parameters using
      both pump and probe and fast repetition rate techniques. In both environments,
      the natural phytoplankton communities displayed marked decreases in PS II
      photochemical energy conversion efficiency that were correlated with increased
      PAR. In the coastal waters, the changes in photochemical energy conversion
      efficiency were not statistically different for samples treated with
      supplementary UV-B radiation or screened to exclude ambient UV-B. Moreover, no
      significant light-dependent changes in the functional absorption cross section of
      PS II were observed. The rate of electron transfer between QA (-) and QB was,
      however, slightly reduced in photodamaged cells, indicative of damage on the
      acceptor side. In the subtropical Pacific, the decrease in photochemical energy
      conversion efficiency was significantly greater for samples exposed to natural
      levels of UV-A and/or UV-B compared with those exposed to PAR alone. The cells
      displayed large diurnal changes in the functional absorption cross section of PS
      II, indicative of non-photochemical quenching in the antenna. The changes in the
      functional absorption cross section were highly correlated with PAR but
      independent of UV radiation. The time course of changes in photochemical
      efficiency reveals that the photoinhibited reaction centers rapidly recover
      (within an hour or two) to their preillumination values. Thus, while we found
      definitive evidence for photoinhibition of PS II photochemistry in both coastal
      and open ocean phytoplankton communities, we did not find any effect of UV-B on
      the former, but a clear effect on the latter. The results of this study indicate
      that the effects of UV-B radiation on phytoplankton photosynthesis are as
      dependent on the radiative transfer properties of the water body and the mixing
      rate, as on the wavelength and energy distribution of the radiation and the
      absorption cross sections of the biophysical targets. 

PMID- 24307469
TI  - Inhibition by ethoxyzolamide of a photoacoustic uptake signal in leaves: Evidence
      for carbonic anhydrase catalyzed CO2-solubilisation.
AB  - A photoacoustic pulse-modulation technique is applied for the study of a CO2
      stimulated gas uptake signal in leaves (Reising and Schreiber, Photosynthe Res
      31: 227-238, 1992). It is shown that this uptake signal can be substantially
      suppressed by application of the carbonic anhydrase inhibitor, ethoxyzolamide, to
      leaf discs. This inhibitor does not affect the O2-evolution signal in air or the
      chlorophyll fluorescence induction pattern at high CO2, when non-saturating light
      intensities are used. On the basis of these findings it is concluded that at
      least a major part of the CO2-stimulated photoacoustic uptake signal results from
      light-modulated CO2-solubilisation catalysed by carbonic anhydrase. Modulated CO2
      solubilisation appears likely to be induced by light driven H(+)-translocation
      from the stroma into the thylakoid lumen. Comparison of the induction patterns of
      chlorophyll fluorescence quenching and the uptake signal suggests a correlation
      between membrane energisation and CO2-uptake. The importance of O2-dependent
      electron flow as a major cause of membrane energisation is discussed. It is
      proposed that in the absence of CO2 the combination of Mehler- and ascorbate
      peroxidase reactions does not result in a photobaric signal, as O2-uptake and O2
      evolution components cancel each other. Two main conclusions, which are of
      considerable importance for future practical applications of the photoacoustic
      method, are drawn from these findings: (1) When high CO2 is applied to leaves,
      the photobaric uptake component may provide a unique means of monitoring the
      function of stromal carbonic anhydrase in vivo. (2) Brief flushing of the
      photoacoustic cell with air may prevent the occurrence of an uptake signal, thus
      allowing a straight-forward deconvolution into photothermal and O2-evolution
      components. 

PMID- 24307470
TI  - Competition between electron acceptors in photosynthesis: Regulation of the
      malate valve during CO2 fixation and nitrite reduction.
AB  - For maximal rates of CO2 assimilation in isolated intact spinach chloroplasts the
      generation of the adequate NADPH/ATP ratio is achieved either by cyclic electron
      flow around photosystem I or by linear electron transport to oxaloacetate,
      nitrite or oxygen (Mehler-reaction). The interrelationships between these poising
      mechanisms turn out to be strictly hierarchical. In the presence of antimycin A,
      an inhibitor of ferredoxin-dependent cyclic electron transport, the reduction of
      both, oxaloacetate and nitrite, but not that of oxygen restores CO2 fixation.
      When oxaloacetate and nitrite are added at low concentrations simultaneously
      during steady-state CO2 fixation, the reduction of nitrite is clearly preferred
      over the reduction of oxaloacetate, but CO2 fixation is not influenced. Nitrite
      reduction is not decreased upon addition of oxaloacetate, but vice versa. This is
      due to the regulation of NADP-malate dehydrogenase activation by electron
      pressure via the ferredoxin/thioredoxin system on the one hand, and by the
      NADPH/(NADP+NADPH) ratio (anabolic reduction charge, ARC) on the other hand. Thus
      the closing of the 'malate valve' prevents drainage of reducing equivalents from
      the chloroplast (1) when a low ARC indicates a high demand for NADPH in the
      stroma and (2) when nitrite reduction reduces the electron pressure at
      ferredoxin. The 'malate valve' is opened when cyclic electron transport is
      inhibited by antimycin A. Under these conditions the rate of malate formation is
      higher than in the absence of the inhibitor even in the presence of oxaloacetate,
      thus indicating that the regulation of the 'malate valve' functions at various
      redox states of the acceptor side of Photosystem I. 

PMID- 24307471
TI  - Erratum.

PMID- 24307472
TI  - Intention to undergo colonoscopy screening among relatives of colorectal cancer
      cases: a theory-based model.
AB  - BACKGROUND: It is recommended that persons having familial risk of colorectal
      cancer begin regular colonoscopy screening at an earlier age than those in the
      general population. However, many individuals at increased risk do not adhere to
      these screening recommendations. PURPOSE: The goal of this study was to examine
      cognitive, affective, social, and behavioral motivators of colonoscopy intention
      among individuals at increased risk of familial colorectal cancer. METHODS:
      Relatives of colorectal cancer cases (N = 481) eligible for colonoscopy screening
      completed a survey assessing constructs from several theoretical frameworks
      including fear appeal theories. RESULTS: Structural equation modeling indicated
      that perceived colorectal cancer risk, past colonoscopy, fear of colorectal
      cancer, support from family and friends, and health-care provider recommendation
      were determinants of colonoscopy intention. CONCLUSIONS: Future interventions to
      promote colonoscopy in this increased risk population should target the factors
      we identified as motivators. (ClinicalTrials.gov number NCT01274143).

PMID- 24307473
TI  - Is being out about sexual orientation uniformly healthy? The moderating role of
      socioeconomic status in a prospective study of gay and bisexual men.
AB  - BACKGROUND: Stress associated with concealing sexual orientation is a possible
      mechanism for health disparities among lesbian, gay, bisexual (LGB) individuals.
      However, disclosing one's sexual orientation might not be uniformly healthy
      across social contexts. PURPOSE: The present study tested whether being out is
      less healthy for gay and bisexual men of lower socioeconomic status (SES)
      relative to higher SES men. METHODS: Using longitudinal data on gay and bisexual
      men (N = 564, ages 18-72), we examined whether the association between outness
      and physical health differs by SES. RESULTS: SES significantly moderated
      associations between outness and physician visits, nonprescription medication
      use, and physical symptoms. Outness predicted physical health benefits for higher
      SES men but health problems for lower SES men. CONCLUSIONS: The common assumption
      that disclosing one's sexual orientation is uniformly healthy may be less
      accurate (or inaccurate) for lower status groups. Future research should explore
      SES as context for minority stress and LGB health disparities.

PMID- 24307474
TI  - The impact of incentives on exercise behavior: a systematic review of randomized
      controlled trials.
AB  - BACKGROUND: The effectiveness of reinforcing exercise behavior with material
      incentives is unclear. PURPOSE: This study aims to conduct a systematic review of
      existing research on material incentives for exercise, organized by incentive
      strategy. METHODS: Ten studies conducted between January 1965 and June 2013
      assessed the impact of incentivizing exercise compared to a non-incentivized
      control. RESULTS: There was significant heterogeneity between studies regarding
      reinforcement procedures and outcomes. Incentives tended to improve behavior
      during the intervention while findings were mixed regarding sustained behavior
      after incentives were removed. CONCLUSIONS: The most effective incentive
      procedure is unclear given the limitations of existing research. The
      effectiveness of various incentive procedures in promoting initial behavior
      change and habit formation, as well as the use of sustainable incentive
      procedures should be explored in future research.

PMID- 24307475
TI  - From waste biomass to solid support: lignosulfonate as a cost-effective and
      renewable supporting material for catalysis.
AB  - Lignosulfonate (LS) is an organic waste generated as a byproduct of the cooking
      process in sulfite pulping in the manufacture of paper. In this paper, LS was
      used as an anionic supporting material for immobilizing cationic species, which
      can then be used as heterogeneous catalysts in some organic transformations. With
      this strategy, three lignin-supported catalysts were prepared including 1) lignin
      SO3 Sc(OTf)2 , 2) lignin-SO3 Cu(OTf), and 3) lignin-IL@NH2 (IL=ionic liquid).
      These solid materials were then examined in many organic transformations. It was
      finally found that, compared with its homogeneous counterpart as well as some
      other solid catalysts that are prepared by using different supports with the same
      metal or catalytically active species, the lignin-supported catalysts showed
      better performance in these reactions not only in terms of activity but also with
      regard to recyclability. 

PMID- 24307476
TI  - Hierarchical copper-decorated nickel nanocatalysts supported on La2O3 for low
      temperature steam reforming of ethanol.
AB  - Copper/nickel nanocatalysts with a unique morphology were prepared by thermal
      reduction of a perovskite LaNix Cu1-x O3 precursor (x=1, 0.9, and 0.7). During
      thermal reduction, copper was first reduced and reacted with lanthanum to form
      metastable Cu5 La and Cu13 La. When the thermal reduction temperature was
      increased, the perovskite decomposed to Ni and La2 O3 , CuLa alloys disappeared,
      and Cu deposits on Ni nanoparticles were generated, thereby forming Cu/Ni
      nanocatalysts with hierarchical structures. Nanosized nickel, decorated with
      copper and supported on La2 O3 , could be produced at 520-550  degrees C. The
      steam reforming of ethanol was used as a model reaction to demonstrate the
      catalytic capability of the materials formed. The hierarchical structure of the
      Cu/Ni/La2 O3 catalysts confers synergetic effects that greatly favor the
      dehydrogenation of ethanol and which break the C-C bond to produce a higher yield
      of hydrogen at a low reaction temperature, whereas La2 O3 provides the required
      stability during the reaction. The reaction at 290  degrees C achieved almost 100
      % conversion with a hydrogen yield reaching 2.21 molH2  mol(-1) EtOH thus
      indicating that this special structural feature can achieve high activity for the
      SRE at low temperatures. The proposed synthesis of nanocatalysts appears to be a
      good way to generate oxide-supported hierarchically structured nanoparticles that
      can also be applied to other reactions catalyzed by a heterogeneous metal oxide
      system.

PMID- 24307477
TI  - Robotic cholecystectomy and resident education: the UC Davis experience.
AB  - INTRODUCTION: The popularity of robotic surgery highlights the need for
      strategies to integrate this technique into surgical education. We present 5 year
      data for robotic cholecystectomy (RC) as a model for training residents. METHODS:
      Data were collected on all RC over 66 months. Duration for docking the robot (S2)
      and performing RC (S3), and surgical outcomes, were recorded. We used a linear
      mixed effects model to investigate learning curves. RESULTS: Thirty-eight
      trainees performed 160 RCs, with most performing more than four. One case was
      aborted due to haemodynamic instability, and two were converted to open surgery
      due to adhesions. There were no technical complications. The duration of S2 (mean
      = 6.2 +/- 3.6 min) decreased considerably (p = 0.027). Trainees also demonstrated
      decrease in duration of S3 (mean = 38.4 +/- 15.4 min), indicating improvement in
      technique (p = 0.008). CONCLUSIONS: RC is an effective model for teaching
      residents. Significant and reproducible improvement can be realized with low risk
      of adverse outcomes.

PMID- 24307478
TI  - Is it safe to withdraw etanercept in established rheumatoid arthritis after low
      disease activity achievement?

PMID- 24307479
TI  - Role of biomaterials in prevention of in-stent restenosis.
AB  - Coronary balloon angioplasty and coronary stenting are the procedures used in
      healing coronary artery disease. However, injury of arteries during angioplasty
      and stenting causes cell stimulations in tissue. Cell movement and thrombosis
      lead to re-narrowing of widened vessel called restenosis. Several new types of
      carriers and technology have been developed to suppress and/or prevent
      restenosis. Authors review the polymeric materials featured in drug/gene carrier
      systems, nanovehicles, and stent coating materials against restenosis.

PMID- 24307480
TI  - The G2019S LRRK2 mutation: another morbid burden for Ashkenazi Jews may provide
      new insights on sporadic Parkinson's disease.

PMID- 24307481
TI  - From the Journal archives: Complications of transurethral prostatic surgery: back
      to the future?

PMID- 24307482
TI  - Genome sequencing of Giardia lamblia genotypes A2 and B isolates (DH and GS) and
      comparative analysis with the genomes of genotypes A1 and E (WB and Pig).
AB  - Giardia lamblia (syn G. intestinalis, G. duodenalis) is the most common
      pathogenic intestinal parasite of humans worldwide and is a frequent cause of
      endemic and epidemic diarrhea. G. lamblia is divided into eight genotypes (A-H)
      which infect a wide range of mammals and humans, but human infections are caused
      by Genotypes A and B. To unambiguously determine the relationship among
      genotypes, we sequenced GS and DH (Genotypes B and A2) to high depth coverage and
      compared the assemblies with the nearly completed WB genome and draft sequencing
      surveys of Genotypes E (P15; pig isolate) and B (GS; human isolate). Our results
      identified DH as the smallest Giardia genome sequenced to date, while GS is the
      largest. Our open reading frame analyses and phylogenetic analyses showed that GS
      was more distant from the other three genomes than any of the other three were
      from each other. Whole-genome comparisons of DH_A2 and GS_B with the optically
      mapped WB_A1 demonstrated substantial synteny across all five chromosomes but
      also included a number of rearrangements, inversions, and chromosomal
      translocations that were more common toward the chromosome ends. However, the
      WB_A1/GS_B alignment demonstrated only about 70% sequence identity across the
      syntenic regions. Our findings add to information presented in previous reports
      suggesting that GS is a different species of Giardia as supported by the degree
      of genomic diversity, coding capacity, heterozygosity, phylogenetic distance, and
      known biological differences from WB_A1 and other G. lamblia genotypes.

PMID- 24307483
TI  - Hoxa5/Cre transgenic mice: novel tools for regional deletion along the anterior
      posterior axis.
AB  - The Hoxa5 homeobox gene encodes a transcription factor that plays a critical role
      in specifying the identity of the cervico-thoracic region along the anterior
      posterior embryo axis and in orchestrating organ morphogenesis. The loss of Hoxa5
      function results in skeletal transformations, lethality at birth due to lung
      defects, and organ anomalies affecting the digestive tract, the mammary gland and
      the ovary. Study of Hoxa5 gene regulation has revealed the interplay of several
      control regions that direct Hoxa5 developmental expression. Enhancers targeting
      expression in the CNS, the paraxial and lateral plate mesoderm at the cervico
      thoracic level, and in the mesenchymal compartment of the respiratory and
      digestive tracts have been identified. Using these molecular tools, we have
      generated two Hoxa5/Cre transgenic mouse lines carrying different combinations of
      Hoxa5 regulatory enhancers and allowing site-specific recombination in subsets of
      Hoxa5 expression sites as tested with the Rosa26/lacZ reporter mice. Further
      validation of the recombination efficiency of the Hoxa5/Cre transgenic lines was
      performed with mice carrying a Hoxa5 conditional allele. Hoxa5 deletion with the
      Hoxa5/Cre mouse lines recapitulates Hoxa5 mutant phenotypes, such as skeletal
      defects, neonatal lethality, and lung malformations. Hoxa5/Cre mouse lines
      provide novel genetic tools for gene function analysis in defined tissues along
      the anterior-posterior axis.

PMID- 24307484
TI  - Synthesis of isotopically labeled epothilones.
AB  - The epothilones, including epothilones B and D, are macrocyclic lactones, which
      have potent cytotoxicities and promote the polymerization of tubulin to
      mictotubules by binding to and stabilizing the tubulin polymer. They have a very
      similar mechanism of action to paclitaxel (Taxol(r)). The determination of the
      microtubule-binding conformation of the epothilones is an important piece of
      information in designing improved analogs for possible clinical use, and
      internuclear distance information that will assist the determination of this
      conformation can be obtained by rotational echo double resonance (REDOR) NMR
      studies of microtubule-bound epothilones with appropriate stable isotope labels.
      Analogs of epothilone B and epothilone D with [(2) H3 ] and [(19) F] labels were
      prepared from an advanced precursor for potential use in REDOR NMR studies to
      determine internuclear distances in tubulin-bound ligand.

PMID- 24307486
TI  - An enzymatic domain for the formation of cyclic ethers in complex polyketides.

PMID- 24307485
TI  - Comparison of treatment modalities for contact granuloma: a nationwide
      multicenter study.
AB  - OBJECTIVES/HYPOTHESIS: This study evaluated the efficacy of commonly used
      treatment modalities and determined predictors of treatment outcome for contact
      granuloma. STUDY DESIGN: Retrospective study. METHODS: Twenty otolaryngologists
      from 18 university hospitals reviewed the medical records of their own contact
      granuloma patients for the most recent 4 years. To be enrolled as a valid case,
      each treatment had to continue for at least 3 months. After excluding intubation
      granuloma, 590 cases of contact granuloma were analyzed. Treatment outcomes were
      assessed as complete response (CR), marked response (MR), partial response (PR),
      and no response. The chi-square test was used to compare the efficacy of each
      treatment modality and logistic regression to determine the predictors of
      treatment outcome. RESULTS: The long-term outcomes of good response (GR) (sum of
      CR and MR) rates after each treatment were 20.5% for observation, 31.6% for
      steroid inhalation, 44.0% for proton pump inhibitor (PPI), 44.3% for voice
      therapy, 60.0% for surgical removal, and 74.2% for botulinum toxin injection.
      Voice therapy, PPI, and botulinum toxin had more good responses than simple
      observation for the long-term outcome (P < 0.05). Surgical removal had a
      significantly higher recurrence rate (37.1%) than simple observation (10.3%) (P <
      0.05). CONCLUSIONS: Voice therapy or PPI are recommended as first-line
      treatments. Surgical removal should be reserved for selected patients because of
      the high chance of recurrence. Botulinum toxin injection can be used not only for
      primary cases but also for refractory cases with an expected high response rate.

PMID- 24307487
TI  - Treatment of hypertension in peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) causes considerable morbidity and
      mortality. Hypertension is a risk factor for PAD. Treatment for hypertension must
      be compatible with the symptoms of PAD. Controversy regarding the effects of beta
      adrenoreceptor blockade for hypertension in patients with PAD has led many
      physicians to stop prescribing beta-adrenoreceptor blockers. Little is known
      about the effects of other classes of anti-hypertensive drugs in the presence of
      PAD. This is the second update of a Cochrane review first published in 2003.
      OBJECTIVES: To determine the effects of anti-hypertensive drugs in patients with
      both raised blood pressure and symptomatic PAD in terms of the rate of
      cardiovascular events and death, symptoms of claudication and critical leg
      ischaemia, and progression of atherosclerotic PAD as measured by ankle brachial
      index (ABI) changes and the need for revascularisation (reconstructive surgery or
      angioplasty) or amputation. SEARCH METHODS: For this update the Cochrane
      Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the
      Cochrane Peripheral Vascular Diseases Group Specialised Register (last searched
      March 2013) and CENTRAL (2013, Issue 2). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) of at least one anti-hypertensive treatment against
      placebo or two anti-hypertensive medications against each other, with
      interventions lasting at least one month. Trials had to include patients with
      symptomatic PAD. DATA COLLECTION AND ANALYSIS: Data were extracted by one author
      (DAL) and checked by the other (GYHL). Potentially eligible studies were excluded
      when the results presentation prevented adequate extraction of data and enquiries
      to authors did not yield raw data. MAIN RESULTS: Eight RCTs were included with a
      total of 3610 PAD patients. Four studies compared a recognised class of anti
      hypertensive treatment with placebo and four studies compared two anti
      hypertensive treatments with each other. Studies were not pooled due to the
      variation of the comparisons and the outcomes presented. Overall the quality of
      the available evidence was unclear, primarily as a result of a lack of detail in
      the study reports on the randomisation and blinding procedures and incomplete
      outcome data. Two studies compared angiotensin converting enzyme (ACE) inhibitors
      against placebo. In one study there was a significant reduction in the number of
      cardiovascular events in patients receiving ramipril (odds ratio (OR) 0.72, 95%
      confidence interval (CI) 0.58 to 0.91; n = 1725). In the second trial using
      perindopril (n = 52) there was a marginal increase in claudication distance but
      no change in ABI and a reduction in maximum walking distance. A trial comparing
      the calcium antagonist verapamil versus placebo in patients undergoing
      angioplasty (n = 96) suggested that verapamil reduced restenosis (per cent
      diameter stenosis (+/- SD) 48.0% +/- 11.5 versus 69.6% +/- 12.2; P < 0.01),
      although this was not reflected in the maintenance of a high ABI (0.76 +/- 0.10
      versus 0.72 +/- 0.08 for verapamil versus placebo). Another study (n = 80)
      demonstrated no significant difference in arterial intima-media thickness (IMT)
      in men receiving the thiazide diuretic hydrochlorothiazide (HCTZ) compared to
      those receiving the alpha-adrenoreceptor blocker doxazosin (-0.12 +/- 0.14 mm and
      -0.08 +/- 0.13 mm, respectively; P = 0.66). A study (n = 36) comparing
      telmisartan to placebo found a significant improvement in maximum walking
      distance at 12 months with telmisartan (median (interquartile range (IQR)) 191 m
      (157 to 226) versus 103 m (76 to 164); P < 0.001) but no differences in ABI
      (median (IQR) 0.60 (0.60 to 0.77) versus 0.52 (0.48 to 0.67)) or arterial IMT
      (median (IQR) 0.08 cm (0.07 to 0.09) versus 0.09 cm (0.08 to 0.10)). Two studies
      compared the beta-adrenoreceptor blocker nebivolol with either the thiazide
      diuretic HCTZ or with metoprolol. Both studies found no significant differences
      in intermittent or absolute claudication distance, ABI, or all-cause mortality
      between the anti-hypertensives. A subgroup analysis of PAD patients (n = 2699) in
      a study which compared a calcium antagonist-based strategy (verapamil slow
      release (SR) +/- trandolapril) to a beta-adrenoreceptor blocker-based strategy
      (atenolol +/- hydrochlorothiazide) found no significant differences in the
      composite endpoints of death, non-fatal myocardial infarction or non-fatal stroke
      with or without revascularisation (OR 0.90, 95% CI 0.76 to 1.07 and OR 0.96, 95%
      CI 0.82 to 1.13, respectively). AUTHORS' CONCLUSIONS: Evidence on the use of
      various anti-hypertensive drugs in people with PAD is poor so that it is unknown
      whether significant benefits or risks accrue. However, lack of data specifically
      examining outcomes in PAD patients should not detract from the overwhelming
      evidence on the benefit of treating hypertension and lowering blood pressure.

PMID- 24307488
TI  - Pooled population pharmacokinetic analysis of phase I, II and III studies of
      linifanib in cancer patients.
AB  - BACKGROUND AND OBJECTIVE: Linifanib is a multi-targeted receptor tyrosine kinase
      inhibitor, which can inhibit members of the vascular endothelial growth factor
      and platelet-derived growth factor receptor families. The objective of this
      analysis was to characterize the population pharmacokinetics of linifanib in
      cancer patients. METHODS: We pooled 7,351 linifanib plasma concentrations from
      1,010 cancer patients enrolled in 13 clinical studies. Population pharmacokinetic
      modelling was performed using NONMEM version 7.2. The covariates that were
      screened included the cancer type, co-medications, creatinine clearance,
      formulation, fed status, liver function markers (bilirubin, blood urea nitrogen
      [BUN], aspartate aminotransferase [AST], alanine aminotransferase [ALT]),
      albumin, age, sex, race, body weight, surface area and body mass index. RESULTS:
      A two-compartment model with first-order absorption and disposition best
      described linifanib pharmacokinetics. An increase in body weight was associated
      with less than proportional increases in volumes of distribution. Subjects with
      hepatocellular carcinoma and renal cell carcinoma were estimated to have 63 and
      86% larger volumes of distribution, respectively, than subjects with the other
      cancer types. Females had 25% slower oral clearance (CL/F) than males, while
      subjects with colorectal cancer had 41% faster CL/F than other subjects. For
      linifanib bioavailability, subjects with refractory acute myeloid leukaemia or
      myelodysplastic syndrome had 43% lower bioavailability, evening doses were
      associated with 27% lower bioavailability than morning doses, and administration
      of linifanib under fed conditions decreased the bioavailability by 14%. Finally,
      the oral solution formulation showed two-fold faster absorption than the tablet
      formulations. CONCLUSION: The use of mixed-effects modelling allowed robust
      assessment of the impact of the concomitant effects of body size, different
      cancer types, formulation, diurnal variation, sex and food on linifanib
      pharmacokinetics. The developed population pharmacokinetic model describes
      linifanib concentrations adequately and can be used to conduct simulations or to
      evaluate the linifanib exposure-response relationship.

PMID- 24307489
TI  - Anhedonia and pain avoidance in the suicidal mind: behavioral evidence for
      motivational manifestations of suicidal ideation in patients with major
      depressive disorder.
AB  - OBJECTIVES: Psychological pain may be helpful in conceptualizing suicidal
      behavior, in that high motivation to avoid pain combined with painful feelings
      may contribute to an increased risk of suicide. However, no experimental study
      has tested this hypothesis. The aim of the present study is to provide empirical
      evidence for the relationship between anhedonia, pain avoidance motivation, and
      suicidal ideation. METHOD: The sample comprised 40 depressed outpatients and 20
      healthy control subjects. All participants completed the Beck Scale for Suicide
      Ideation (BSS), Beck Depression Inventory, Psychache Scale, Three-Dimensional
      Psychological Pain Scale, the monetary incentive delay (MID), and affective
      incentive delay (AID) tasks. Based on BSS scores, clinical participants were
      divided into high suicidal ideation (HSI) and low suicidal ideation (LSI) groups.
      RESULTS: In the AID task, the HSI group had longer response times (RTs) under the
      reward condition than those under the punishment condition (p = .002). The LSI
      and control groups had shorter RTs under the reward condition compared with those
      under the neural condition (p <.001 and p = .008, respectively). The LSI group
      also had shorter RTs under the reward condition than under the punishment
      condition (p = .003). Pain arousal (r = -.33, p <.01) and BSS scores were
      significantly negatively correlated with differences in RTs between neutral and
      reward conditions. Pain avoidance (r = .35, p <.01) and BSS scores were
      positively correlated with differences in RTs between neutral and punishment
      conditions. CONCLUSIONS: The AID task was more sensitive than the MID task for
      the detection of participants' motivation in approaching hedonic experiences and
      avoiding pain. A suicidal mindset is manifested as decreased motivation to
      experience hedonia and increased motivation to avoid pain, which could be strong
      predictors of suicidal behavior.

PMID- 24307490
TI  - Attentional modulation of reward processing in the human brain.
AB  - Although neural signals of reward anticipation have been studied extensively, the
      functional relationship between reward and attention has remained unclear: Neural
      signals implicated in reward processing could either reflect attentional biases
      towards motivationally salient stimuli, or proceed independently of attentional
      processes. Here, we sought to disentangle reward and attention-related neural
      processes by independently modulating reward value and attentional task demands
      in a functional magnetic resonance imaging study in healthy human participants.
      During presentation of a visual reward cue that indicated whether monetary reward
      could be obtained in a subsequent reaction time task, participants either
      attended to the reward cue or performed an unrelated attention-demanding task at
      two different levels of difficulty. In ventral striatum and ventral tegmental
      area, neural responses were modulated by reward anticipation irrespective of
      attentional demands, thus indicating attention-independent processing of reward
      cues. By contrast, additive effects of reward and attention were observed in
      visual cortex. Critically, reward-related activations in right anterior insula
      strongly depended on attention to the reward cue. Dynamic causal modelling
      revealed that the attentional modulation of reward processing in insular cortex
      was mediated by enhanced effective connectivity from ventral striatum to anterior
      insula. Our results provide evidence for distinct functional roles of the brain
      regions involved in the processing of reward-indicating information: While
      subcortical structures signal the motivational salience of reward cues even when
      attention is fully engaged elsewhere, reward-related responses in anterior insula
      depend on available attentional resources, likely reflecting the conscious
      evaluation of sensory information with respect to motivational value.

PMID- 24307491
TI  - Tips for double balloon enteroscopy in patients with Roux-en-Y reconstruction and
      modified child surgery.
AB  - Pancreatobiliary disease in patients with altered anatomic intestine is one of
      the most difficult cases for pancreatobiliary endoscopic therapies and diagnosis.
      There are two major challenges to overcome to complete the procedure. The first
      challenge is the deep insertion to the blind end. The second challenge is the
      endoscopic retrograde cholangiopancreatography (ERCP)-related intervention.
      Impairing either success means the incompletion of the procedure. The double
      balloon enteroscope (DBE), which has been recently developed, enabled the deep
      intubation to the blind end. Especially, using the scopes with a short working
      length allowed us to perform the ERCP-related interventions with a high success
      rate. Generally, ERCP using double balloon endoscope (DB-ERCP) in patients with
      altered gastrointestinal anatomy has been established. We introduce our standard
      technique for DB-ERCP and provide several tips for insuring a successful
      procedure. 

PMID- 24307492
TI  - Impact of nodal ratio on survival in recurrent nasopharyngeal carcinoma.
AB  - BACKGROUND: The purpose of this study was to investigate if nodal ratio has a
      prognostic role in the survival of patients with recurrent nasopharyngeal
      carcinoma (NPC) in the neck. METHODS: Patients with recurrent NPC in the neck who
      were treated in Queen Mary Hospital from 2000 to 2011 were identified. Clinical
      data, pathological results, and survival outcome were analyzed. RESULTS: Only
      nodal ratio remained as a statistically significant predictor in multivariate
      analysis for nodal recurrence (p = .045) and nodal recurrence-free survival (p =
      .010). All other predictors lost significance when compared with each other and
      with nodal ratio. Nodal ratio was also a significant predictor for overall
      survival (OS) in univariate analysis (p = .001) but lost its significance in
      multivariate analysis. The cutoff points 10% and 15% effectively stratified the
      patients into 3 risk groups (p = .02). CONCLUSION: In patients with NPC with neck
      recurrence, nodal ratio (the ratio of positive nodes to the total number of nodes
      examined) is a strong predictor of further nodal recurrence and nodal recurrence
      free survival. Nodal ratio also impacts the OS but loses its significance in
      multivariate analysis, including concurrent local recurrence. Stratification of
      patients into low, medium, and high-risk groups according to nodal ratio may have
      a potential role in guiding therapeutic decision-making. Therefore, further
      exploration in this area is warranted.

PMID- 24307493
TI  - Bioorthogonal chemistry for (68) Ga radiolabelling of DOTA-containing compounds.
AB  - Copper-catalysed 'click' chemistry is a highly utilised technique for
      radiolabelling small molecules and peptides for imaging applications. The
      usefulness of these reactions falls short, however, when metal catalysis is not a
      practically viable route; such as when using metal chelates as radioligands.
      Here, we describe a method for carrying out 'click-type' radiochemistry in the
      presence of DOTA chelates, by combining (68) Ga radiolabelling techniques with
      well-established bioorthogonal reactions, which do not rely upon metal catalysis.

PMID- 24307494
TI  - Short-term biliary stenting before mechanical lithotripsy for difficult bile duct
      stones.
AB  - BACKGROUND AND STUDY AIM: Short-term common bile duct stenting has been shown to
      decrease stone size, but its effect on mechanical lithotripsy has not been
      reported. PATIENTS AND METHODS: Sixty patients of difficult bile duct stones were
      subjected to mechanical lithotripsy. Thirty patients were subjected to mechanical
      lithotripsy at the time of first endoscopic retrograde cholangiopancreatography
      (group A) while another 30 patients were subjected to mechanical lithotripsy
      using trapezoid basket after a short period of stenting (group B). The effect on
      the hardness of stone, durability of the basket after stenting, and duration of
      mechanical lithotripsy was studied. RESULTS: Lithotripsy after stenting was less
      time consuming, and durability of the basket was much more in comparison to
      lithotripsy without stenting (p < 0.001). Friability of stone increased after
      stenting, and it was easy to break the stone after preliminary stenting.
      CONCLUSION: Short-term (2 to 3 months) stenting should be done in all the
      patients with large stones before subjecting them to mechanical lithotripsy to
      make the procedure less time consuming and more convenient to endoscopist.

PMID- 24307495
TI  - Chemoembolization of intermediate stage hepatocellular carcinomas: results from a
      Nordic tertiary liver cancer center.
AB  - BACKGROUND: Transarterial chemoembolization (TACE) is used as palliative
      treatment of hepatocellular carcinoma (HCC). Most publications are from HCC
      patient populations where viral hepatitis is the primary cause of liver disease.
      In the Nordic countries, most patients have either alcohol-induced cirrhosis or
      are noncirrhotic. The aim of this single-center study was to evaluate patient
      characteristics, survival, and side effects of TACE in a Danish referral center
      for HCC treatment. METHODS: Fifty-nine consecutive patients with HCC, treated
      with TACE, either chemoembolization with drug-eluting beads or conventional-TACE
      with Lipiodol, were included in the study. Their medical records were
      retrospectively reviewed, computed tomography images analyzed, and biochemical
      markers recorded. The primary endpoint was overall survival. Analyses were by
      intention to treat. RESULTS: Thirty-five patients (59 %) had HCC on a background
      of liver cirrhosis most often caused by alcohol (60 % of cirrhotics or 35 %
      overall). Before the first chemoembolization, the patients had a median Child
      Pugh score of 6 (5-7) and a median MELD score of 10 (6-21). Median survival after
      chemoembolization was 18.9 months (13.1-24.7). TACE patients were hospitalized
      for an average of 3 days (2-30). Prolonged stay was most often due to side
      effects-eg. pain (31 %), fever (14 %), nausea (10 %), and infection (10 %).
      Thirty-three patients (56 %) did not have any side effects. CONCLUSIONS: In this
      cohort, we observed an acceptable survival following TACE without significant
      side effects.

PMID- 24307496
TI  - A MALDI MS investigation of the lysophosphatidylcholine/phosphatidylcholine ratio
      in human spermatozoa and erythrocytes as a useful fertility marker.
AB  - The human spermatozoa membrane is characterized by a unique fatty acyl
      composition with significant amounts of highly unsaturated fatty acids,
      particularly docosahexaenoic acid (22:6), whereby phosphatidylcholine (PtdCho)
      (16:0/22:6) is the most abundant glycerophospholipid. The large amount of highly
      unsaturated fatty acyl residues is crucial for the fluidity of the membrane and,
      therefore, the successful fertilization process. Consequently, however, the
      spermatozoa are very sensitive to reactive oxygen species (ROS) that are
      generated under conditions of "oxidative stress" and key players in many
      pathological conditions. Lipid oxidation of the sperm membrane is accompanied by
      the loss of the oxidatively modified unsaturated residue (normally in the sn-2
      position) and the generation of saturated lysophosphatidylcholine (LysoPtdCho).
      Although other lysolipids are also generated, LysoPtdCho is the "marker" lipid of
      choice due to the high abundance of PtdCho. In particular, obesity (body mass
      index >30 kg/m(2)) is characterized by increased ROS generation and negatively
      affects the reproductive potential. We will show here that the LysoPtdCho/PtdCho
      ratio can be easily determined by matrix-assisted laser desorption/ionization
      time of flight mass spectrometry (MALDI-TOF MS). The data found do correlate with
      clinical markers of sperm quality. A very interesting aspect is that the
      LysoPtdCho/PtdCho ratios determined in the spermatozoa extracts correlate with
      the LysoPtdCho/PtdCho values determined in the organic extracts of erythrocytes.
      Thus, there is no absolute need for a sperm investigation, but an estimation of
      the fertilizing ability of the corresponding male could be also made directly
      from the blood which is more readily available than the spermatozoa. 

PMID- 24307497
TI  - Effects of bone marrow-derived mesenchymal stem cells and platelet-rich plasma on
      bone regeneration for osseointegration of dental implants: preliminary study in
      canine three-wall intrabony defects.
AB  - Tissue engineering has been applied to overcome the obstacles encountered with
      bone regeneration for the placement of dental implants. The purpose of this study
      was to determine the bone formation ability of human bone marrow-derived
      mesenchymal stem cells (BMMSCs) and platelet-rich plasma (PRP) when applied
      separately or together to the intrabony defect around dental implants with a
      porous hydroxyapatite (HA) scaffold. Standardized three-wall intrabony defects (4
      * 4 * 4 mm) were created at the mesial of each dental implant site in four
      mongrel dogs. Defects were then grafted with the following materials: HA + BMMSCs
      (HS group), HA + PRP (HP group), HA + BMMSCs + PRP (HSP group), and HA scaffold
      alone (HA group). The level of bone formation (bone density) and osseointegration
      (bone-to-implant contact [BIC]) in bone defects around the implants were
      evaluated by histological and histometric analysis at 6 and 12 weeks after the
      placement of implants. HA, HS, HP, and HSP groups generally showed an increase in
      bone density and BIC between 6 and 12 weeks, except BIC in the HS group. Although
      no statistically significant differences were found among HA, HS, HP, and HSP
      groups (p > 0.05), the highest level of bone density and BIC were observed in the
      HSP group after the 12-week healing period. Furthermore, the level of bone
      maturation was higher in the HSP group than in the other groups as determined
      histologically. The findings of this preliminary study suggest that BMMSCs and
      PRP combined with HA scaffold may provide additional therapeutic effects on bone
      regeneration and improve osseointegration in bone defects around dental implants.

PMID- 24307498
TI  - Characterization of the co-purified invertase and beta-glucosidase of a
      multifunctional extract from Aspergillus terreus.
AB  - The filamentous fungus Aspergillus terreus secretes both invertase and beta
      glucosidase when grown under submerged fermentation containing rye flour as the
      carbon source. The aim of this study was to characterize the co-purified
      fraction, especially the invertase activity. An invertase and a beta-glucosidase
      were co-purified by two chromatographic steps, and the isolated enzymatic
      fraction was 139-fold enriched in invertase activity. SDS-PAGE analysis of the co
      purified enzymes suggests that the protein fraction with invertase activity was
      heterodimeric, with subunits of 47 and 27 kDa. Maximal invertase activity, which
      was determined by response surface methodology, occurred in pH and temperature
      ranges of 4.0-6.0 and 55-65  degrees C, respectively. The invertase in co
      purified enzymes was stable for 1 h at pH 3.0-10.0 and maintained full activity
      for up to 1 h at 55  degrees C when diluted in water. Invertase activity was
      stimulated by 1 mM concentrations of Mn2+ (161 %), Co2+ (68 %) and Mg2+ (61 %)
      and was inhibited by Al3+, Ag+, Fe2+ and Fe3+. In addition to sucrose, the co
      purified enzymes hydrolyzed cellobiose, inulin and raffinose, and the apparent
      affinities for sucrose and cellobiose were quite similar (K(M) = 22 mM). However,
      in the presence of Mn2+, the apparent affinity and V(max) for sucrose hydrolysis
      increased approximately 2- and 2.9-fold, respectively, while for cellobiose, a
      2.6-fold increase in V(max) was observed, but the apparent affinity decreased 5.5
      fold. Thus, it is possible to propose an application of this multifunctional
      extract containing both invertase and beta-glucosidase to degrade plant biomass,
      thus increasing the concentration of monosaccharides obtained from sucrose and
      cellobiose.

PMID- 24307499
TI  - Effect of copper-induced oxidative stress on sclerotial differentiation and
      antioxidant properties of Penicillium thomii PT95 strain.
AB  - Penicillium thomii PT95 strain was able to form abundant orange, sand-shaped
      sclerotia in which carotenoids were accumulated. The aim of this work was to
      determine the effects of copper-induced oxidative stress on the sclerotial
      differentiation and antioxidant properties of PT95 strain. The results showed
      that the time of exudates initiation, sclerotial initiation and sclerotial
      maturation of PT95 strain were advanced in 1-2 days under the copper-induced
      oxidative stress growth conditions. The analytical results of sclerotial biomass,
      carotenoids content in sclerotia showed that copper-induced oxidative stress
      favored the sclerotial differentiation and biosynthesis of carotenoids. Under the
      copper-induced oxidative stress growth conditions, the total phenolics content
      and DPPH free radical scavenging activity of sclerotia of this fungus were
      decreased as compared with the control. However, the oxidative stress induced by
      a lower amount of CuSO4 in media could enhance significantly the reducing power
      of sclerotia.

PMID- 24307500
TI  - Looking into the crystal ball: the 60-5 criterion--a newly proposed predictor of
      severe complications after liver transplantation.

PMID- 24307501
TI  - Significant substituent effect on the anomerization of pyranosides: mechanism of
      anomerization and synthesis of a 1,2-cis glucosamine oligomer from the 1,2-trans
      anomer.
AB  - Aminoglycosides containing a 2,3-trans carbamate group easily undergo
      anomerization from the 1,2-trans glycoside to the 1,2-cis isomer under mild
      acidic conditions. The N-substituent of the carbamate has a significant effect on
      the anomerization reaction; in particular, an N-acetyl group facilitated rapid
      and complete alpha-anomerization. The differences in reactivity due to the
      various N-substituents were supported by the results of DFT calculations; the
      orientation of the acetyl carbonyl group close to the anomeric position was found
      to contribute significantly to the directing of the anomerization reaction. By
      exploiting this reaction, oligoaminoglycosides with multiple 1,2-cis glycosidic
      bonds were generated from 1,2-trans glycosides in a one-step process. 

PMID- 24307502
TI  - Perioperative only versus extended antimicrobial usage in tympanomastoid surgery:
      a randomized trial.
AB  - OBJECTIVES/HYPOTHESIS: Antimicrobial prophylaxis is still a matter of debate in
      ear surgeries. Previous studies have focused on prophylaxis in middle ear surgery
      alone without inclusion of mastoidectomy. We therefore investigated efficacy of
      two regimes of antimicrobial prophylaxis in tympanoplasty with cortical
      mastoidectomy done for mild middle ear disease in chronic otitis media. STUDY
      DESIGN: Prospective, randomized, controlled, double-blind study. METHODS:
      Patients undergoing tympanoplasty with cortical mastoidectomy were included and
      randomized into two study groups. The group I patients received parenteral
      perioperative antimicrobials; only group II patients received additional extended
      oral antimicrobials for 8 days more postoperatively. Primary outcomes evaluated
      were postaural wound infection and graft success, assessed weekly until 1 month.
      Adverse events and length of hospital stay were evaluated as secondary outcome.
      RESULTS: Seventy-eight patients were randomized into group I (n = 39) and group
      II (n = 39). The two groups showed no difference in wound infection rate. The
      graft success rate in both the group was comparable (94.87% in group I and 97.44%
      in group II, respectively; P = 1.00). The length of hospital stay was
      significantly longer (P = 0.00001) in group II (3.05 [0.72], mean [SD]) as
      compared to group I (2.36 [0.49]). During the first postoperative week, a
      significantly higher incidence of gastrointestinal disturbances were observed in
      group II (19 [48.72%] as compared to 1 [2.56%] in group I, P = 0.00001).
      CONCLUSION: The present study shows that there is no need of extended
      antimicrobial prophylaxis for tympanoplasty with cortical mastoidectomy done for
      mild middle ear disease. An indiscriminate use of antimicrobials may lead to
      increase incidence of adverse events and prolonged hospital stay. LEVEL OF
      EVIDENCE: 1b.

PMID- 24307503
TI  - Volatile organic compounds from fungi isolated after hurricane katrina induce
      developmental defects and apoptosis in a Drosophila melanogaster model.
AB  - In previous work, our laboratory developed a Drosophila model for studying the
      adverse effects of fungal volatile organic compounds (VOCs) emitted by growing
      cultures of molds. In this report, we have extended these studies and compared
      the toxic effects of fungal VOCs emitted from living cultures of four molds
      isolated after Hurricane Katrina from a flooded home in New Orleans. Strains of
      Aspergillus, Mucor, Penicillium, and Trichoderma were grown with wild-type larvae
      and the toxic effects of volatile products on the developmental stages of
      Drosophila larvae were evaluated. Furthermore, heterozygous mutants of Drosophila
      carrying the apoptotic genes, reaper and dronc, were used to assess the role of
      apoptosis in fungal VOCs mediated toxicity. Third-instar larvae of Drosophila
      carrying these apoptotic genes were exposed to fungal VOCs emitted from growing
      mold cultures for 10 days. The larval strains carrying apoptopic genes survived
      longer than the control wild type larvae; moreover, of those that survived,
      heterozygous reaper and dronc strains progressed to pupae and adult phases more
      rapidly, suggesting that fungal VOCs may induce apoptotic changes in flies. These
      data lend support to the use of Drosophila as an inexpensive and genetically
      versatile toxicological model to investigate the mechanistic basis for some of
      the human illnesses/symptoms associated with exposure to mold-contaminated indoor
      air, especially after hurricanes.

PMID- 24307504
TI  - Carborane-based carbonic anhydrase inhibitors.
AB  - CA inhibitors: Human carbonic anhydrases (CAs) are diagnostic and therapeutic
      targets. Various carborane cages are shown to act as active-site-directed
      inhibitors, and substitution with a sulfamide group and other substituents leads
      to compounds with high selectivity towards the cancer-specific isozyme IX.
      Crystal structures of the carboranes in the active site provide information that
      can be applied to the structure-based design of specific inhibitors. 

PMID- 24307505
TI  - Retinal injury thresholds for 532, 578, and 630 nm lasers in connection to
      photodynamic therapy for choroidal neovascularization.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to explore the retinal
      injury thresholds in rabbits and evaluate the influence of retinal pigmentation
      on threshold irradiance at laser wavelengths of 532, 578, and 630 nm which might
      be involved in hypocrellin B (HB) and hematoporphyrin monomethyl ether (HMME)
      photodynamic therapy (PDT) for choroidal neovascularization (CNV). MATERIALS AND
      METHODS: The eyes of pigmented and non-pigmented rabbits were exposed to 532,
      578, and 630 nm lasers coupled to a slit lamp biological microscope. The exposure
      duration was 100 seconds and the retinal spot size was 2 mm throughout the
      experiment. The minimum visible lesions were detected by funduscopy at 1 and 24
      hours post exposure. Bliss probit analysis was performed to determine the ED50
      thresholds, fiducial limits and probit slope. RESULTS: In pigmented rabbits, the
      24-hour retinal threshold irradiances at 532, 578, and 630 nm were 1,003, 1,475,
      and 1,720 mW/cm(2) , respectively. In non-pigmented rabbits, the 24-hour
      threshold irradiances were 1,657, 1,865, and 15,360 mW/cm(2) , respectively. The
      ED50 for 24-hour observation differed very little from the ED50 for 1-hour
      observation. The non-pigmented rabbits required a ninefold increase in threshold
      irradiance at 630 nm comparing to the pigmented rabbits. CONCLUSION: This study
      will contribute to the knowledge base for the limits of laser irradiance in
      application of HB or HMME PDT for CNV.

PMID- 24307506
TI  - In vivo testing of silver treated fibers for the evaluation of skin irritation
      effect and hypoallergenicity.
AB  - Textiles are a fertile breeding ground for a multitude of micro-organisms under
      appropriate conditions of moisture and temperature. The broad-spectrum biocide
      properties of silver are well known and many technologies have been developed so
      far to treat textiles with silver. The efficacy of the silver deposition
      technology presented in this article has been already demonstrated in previous
      works, where the strong adhesion of silver nanoparticles to the substrate and
      their antibacterial capability have been assessed. This work focuses on the
      evaluation of any possible interaction of silver treated cotton with human skin,
      in terms of skin irritation and hypoallergenicity. Moreover, the presence of
      silver and the antibacterial capability against Gram positive and Gram negative
      bacteria, namely Staphylococcus aureus and Escherichia coli, were verified even
      after several washing cycles in order to develop a product with long-term
      antibacterial capability and no adverse effects in terms of skin irritation and
      hypoallergenicity.

PMID- 24307507
TI  - Synthesis and in vivo evaluation of (11) C-labeled (1,7-dicarba-closo-dodecaboran
      1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide.
AB  - Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as
      hydrophobic pharmacophores in the design of new drugs and radiotracers because of
      their hydrophobic character, spherical structure, and excellent chemical and
      photochemical stability. In the present paper, the synthesis and in vivo
      evaluation of (11) C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1
      ethylpyrrolidin-2-yl]methyl}amide, an analog of the D2 receptor ligand [(11)
      C]raclopride, is described. The radiosynthesis was approached by reaction of the
      demethylated precursor with [(11) C]CH3 I in basic media; moderate radiochemical
      yields (18.2 +/- 2.8%, decay corrected), and excellent radiochemical purities
      (>98%) were obtained in overall synthesis time of ~50 min. In vivo assays showed
      a biodistribution pattern with significant uptake in liver, kidneys and lungs at
      short times (t = 4 min) after administration and increasing accumulation in
      bladder at longer times (t >= 14.5 min). Although brain positron emission
      tomography scans showed good blood brain barrier penetration, the high unspecific
      uptake observed in different brain regions impedes its applicability as D2
      receptor ligand.

PMID- 24307509
TI  - Public attitudes regarding the use of electronic health information and residual
      clinical tissues for research.
AB  - Use of electronic medical records (EMR) and residual clinical biospecimens have
      become important for the conduct of biomedical research. Currently, human
      subjects' protection regulations permit much of this research to be conducted
      without individual informed consent, posing a risk to biomedical research from
      public objection. We sought to understand public attitudes regarding access to
      EMRs and residual clinical biospecimens. This article reports the results of 12
      focus groups with 131 participants conducted in Utah, Washington, Arizona, and
      Minnesota. Results indicate strong support for biomedical and genetic research in
      general and clear support for improved patient education regarding research
      access to individual data and biospecimens. Our participants were supportive of
      an opt-out approach to patient decision-making regarding research access to
      clinical data and biospecimens for research in general. 

PMID- 24307508
TI  - MOZ-mediated repression of p16(INK) (4) (a) is critical for the self-renewal of
      neural and hematopoietic stem cells.
AB  - Although inhibition of p16(INK4a) expression is critical to preserve the
      proliferative capacity of stem cells, the molecular mechanisms responsible for
      silencing p16(INK4a) expression remain poorly characterized. Here, we show that
      the histone acetyltransferase (HAT) monocytic leukemia zinc finger protein (MOZ)
      controls the proliferation of both hematopoietic and neural stem cells by
      modulating the transcriptional repression of p16(INK4a) . In the absence of the
      HAT activity of MOZ, expression of p16(INK4a) is upregulated in progenitor and
      stem cells, inducing an early entrance into replicative senescence. Genetic
      deletion of p16(INK4a) reverses the proliferative defect in both Moz(HAT) (-) (/)
      (-) hematopoietic and neural progenitors. Our results suggest a critical
      requirement for MOZ HAT activity to silence p16(INK4a) expression and to protect
      stem cells from early entrance into replicative senescence.

PMID- 24307510
TI  - Current status of the hybrid approach for the treatment of hypoplastic left heart
      syndrome.
AB  - The hybrid approach for hypoplastic left heart syndrome (HLHS), consisting of
      bilateral pulmonary artery banding and ductal stenting, has emerged as an
      alternative to the traditional Norwood approach. This approach defers open heart
      surgery to beyond the neonatal period, which is believed to reduce postoperative
      mortality and morbidity and improve neurological development as compared with the
      conventional approach. However, there have been no scientific studies supporting
      these hypotheses. Recently, there seems to be a tendency that many centers
      recommend the hybrid approach as an interim procedure to rescue preoperative high
      risk patients. Currently, the decision to adopt the hybrid approach or the
      Norwood approach seemed to be based on the preference of congenital heart
      surgeons and cardiologists. Further investigation including a randomized multi
      center study would allow a scientific decision as to which approach is more
      appropriate for the patient with HLHS. 

PMID- 24307511
TI  - Well-dispersed CoS nanoparticles on a functionalized graphene nanosheet surface:
      a counter electrode of dye-sensitized solar cells.
AB  - With a facile electrophoretic deposition and chemical bath process, CoS
      nanoparticles have been uniformly dispersed on the surface of the functionalized
      graphene nanosheets (FGNS). The composite was employed as a counter electrode of
      dye-sensitized solar cells (DSSCs), which yielded a power conversion efficiency
      of 5.54 %. It is found that this efficiency is higher than those of DSSCs based
      on the non-uniform CoS nanoparticles on FGNS (4.45 %) and built on the naked CoS
      nanoparticles (4.79 %). The achieved efficiency of our cost-effective DSSC is
      also comparable to that of noble metal Pt-based DSSC (5.90 %). Our studies have
      revealed that both the exceptional electrical conductivity of the FGNS and the
      excellent catalytic activity of the CoS nanoparticles improve the conversion
      efficiency of the uniformly FGNS-CoS composite counter electrode. The
      electrochemical impedance spectra, cyclic voltammetry, and Tafel polarization
      have evidenced the best catalytic activity and the fastest electron transport.
      Additionally, the dispersion condition of CoS nanoparticles on FGNS plays an
      important role for catalytic reduction of I3 (-) .

PMID- 24307512
TI  - Tips of laparoscopic pancreaticoduodenectomy: superior mesenteric artery first
      approach (with video).
AB  - In previous reports of laparoscopic pancreaticoduodenectomy, the Kocher maneuver
      with a wide mobilization of the right colonic flexure is carried out in the early
      phase, and dissection of the superior mesenteric artery is performed in the last
      phase of resection. This report describes laparoscopic superior mesenteric artery
      first approach, in which the superior mesenteric artery is dissected in the early
      phase of resection. Through the ligament of Treitz, the retroperitoneum is widely
      opened and the superior mesenteric artery is isolated just superior to the left
      renal vein. The periarterial connective tissue and nerve plexuses surrounding the
      superior mesenteric artery are dissected longitudinally to identify the inferior
      pancreaticoduodenal artery, which is then tied and divided. The superior
      mesenteric artery first approach and early ligation of the inferior
      pancreaticoduodenal artery is considered to be a feasible, safe, and effective
      method for performing pure laparoscopic pancreaticoduodenectomy. 

PMID- 24307513
TI  - A new device to improve the location of a Montgomery thyroplasty prosthesis.

PMID- 24307514
TI  - Thalidomide treatment in a myelofibrosis patient with leukemia transformation.
AB  - Primary myelofibrosis is a clonal disease of chronic myeloproliferative neoplasm,
      and is a progressive clinical course with short median survival of less than 5
      years after diagnosis. Leukemic transformation occurs in 8-23 % of myelofibrosis
      patients, and survival is about 3 months after transformation to leukemia.
      Thalidomide, an oral immunomodulatory drug, has been used effectively in the
      treatment of primary myelofibrosis, in which some patients could become
      transfusion independent, and showed improvement in thrombocytopenia and reduction
      in spleen size. Here, we report a patient with primary myelofibrosis with
      leukemic transformation who survived for more than 6 years with thalidomide
      monotherapy. Thalidomide may be beneficial for some myelofibrosis patients with
      leukemic transformation for whom intensive chemotherapy is not indicated. 

PMID- 24307515
TI  - inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia
      that developed in an elderly woman.
AB  - A 75-year-old woman presented with marked leukocytosis; the white cell count was
      143.6 * 103/MUL with 38.6 % monocytes and 13.6 % immature granulocytes, including
      blasts. Bone marrow (BM) aspirate smears showed >90 % cellularity with
      hyperplasia of myeloid-lineage cells, 14.6 % monocytes, and 32.1 % blasts. The
      granulocyte series showed a range of dysplastic morphologies. The rate of
      peroxidase positivity was 51.5 %. CD36+ cells with monocytic differentiation
      comprised 64.6 % mononuclear cells. Metaphase spreads obtained from the BM
      revealed an aneuploid karyotype with -7 and a submetacentric marker chromosome
      derived from chromosome 2, which was determined to be inv(2)(p23q13) by
      fluorescence in situ hybridization using the Vysis ALK probe. RAN-binding protein
      2 (RANBP2)-ALK fusion mRNA was confirmed by reverse transcriptase-mediated
      polymerase chain reaction and nucleotide sequencing. High-sensitivity anti-ALK
      immunohistochemistry of a BM biopsy specimen demonstrated nuclear membrane
      staining of leukemia cells. As the leukemia showed features of chronic
      myelomonocytic leukemia, the patient was treated with standard daunorubicin
      cytarabine followed by azacitidine, leading to the durable suppression of
      leukemia progression. These findings suggest that inv(2)(p23q13)/RABBP2-ALK
      defines a small subset of myeloid leukemia characterized by differentiation to
      monocytes and sharing features of myelodysplastic syndrome/myeloproliferative
      neoplasm.

PMID- 24307516
TI  - A role for activator of G-protein signaling 3 (AGS3) in multiple myeloma.
AB  - Previous studies have demonstrated that activator of G-protein signaling 3 (AGS3;
      also known as GPSM1), a member of the AGS family, plays an important anti
      apoptotic role through enhancing the phosphorylation of cyclic AMP response
      element-binding protein (p-CREB). In this report, we delineate the anti-apoptotic
      role of AGS3 in multiple myeloma (MM). To do this, we developed a cell apoptotic
      model induced by doxorubicin in MM. Our data indicate that decreased expression
      of AGS3 is correlated with reduced levels of p-CREB in the apoptotic model. The
      negative role of AGS3 in cell apoptosis was further confirmed by knocking down
      AGS3. The microenvironment has been shown to influence tumor cell phenotype in
      response to chemotherapy. Since cell adhesion-mediated drug resistance remains a
      major obstacle for successful treatment of MM, we constructed a cell adhesion
      model in MM and detected the changing of AGS3 protein expression. AGS3 siRNA
      reversed the high rate of MM cell adhesion to either fibronectin or HS-5 cells.
      Consistent with the reduced adhesion rate, the cells also exhibited reduced drug
      resistance to doxorubicin, mitoxantrone, and dexamethasone. Collectively, these
      data indicate that AGS3 may be represented as a good candidate for pursuing
      clinical trials in MM. Moreover, our data provide a clinical therapeutic target
      for MM and potentially other tumors that home and/or metastasize to the bone. 

PMID- 24307517
TI  - Distribution of serum erythropoietin levels in lower risk myelodysplastic
      syndrome cases with anemia.
AB  - International guidelines for myelodysplastic syndrome (MDS) state that the
      standard therapy for lower risk MDS patients with symptomatic anemia of serum
      erythropoietin (EPO) <500 IU/L is erythroid-stimulating agents (ESAs). The
      objective of this study is to examine the distribution of EPO levels in lower
      risk MDS patients, and to inquire into the relationship of EPO distribution to
      hemoglobin levels and transfusions. Twenty cases of lower risk MDS (low or
      intermediate-1 by the International Prognostic Scoring System) with hemoglobin
      level <90 g/L at our institution were enrolled. Eight received more than two
      units of transfusions per month. Median hemoglobin level was 78 g/L. EPO levels
      ranged between 26.4 and 11300 IU/L (median 645 IU/L), including 10 cases (50 %)
      with >500 IU/L. EPO levels were inversely correlated to hemoglobin levels,
      especially in the cases without transfusion support (p < 0.001, R = 0.92). The
      rate of the cases with EPO <500 IU/L was significantly higher in the group
      without transfusion than the others (p = 0.020). Considering that, in Japan, the
      indication for transfusion is around 70 g/L of hemoglobin for chronic diseases,
      it may be possible to improve anemia in a subset of lower risk MDS cases by
      administration of ESAs before transfusions are required.

PMID- 24307518
TI  - Prophylactic antibiotics for inhibiting preterm labour with intact membranes.
AB  - BACKGROUND: The aetiology of preterm birth is complex and there is evidence that
      subclinical genital tract infection influences preterm labour in some women but
      the role of prophylactic antibiotic treatment in the management of preterm labour
      is controversial. Since rupture of the membranes is an important factor in the
      progression of preterm labour, it is important to see if the routine
      administration of antibiotics confers any benefit or causes harm, prior to
      membrane rupture. OBJECTIVES: To assess the effects of prophylactic antibiotics
      administered to women in preterm labour with intact membranes, on maternal and
      neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 August 2013). SELECTION CRITERIA:
      Randomised trials that compared antibiotic treatment with placebo or no treatment
      for women in preterm labour (between 20 and 36 weeks' gestation) with intact
      membranes. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial eligibility, and undertook quality assessment and data extraction.
      We contacted study authors for additional information. Results are presented
      using risk ratio (RR) for categorical data and mean difference (MD) for data
      measured on a continuous scale with their respective 95% confidence intervals
      (CI). The number needed to treat to benefit (NNTB) and the number needed to treat
      to harm (NNTH) was calculated where appropriate. MAIN RESULTS: In this update
      (2013), with the addition of three trials (305 women), the large ORACLE II 2001
      trial continues to dominate the results of this review. This review now includes
      a total of 14 studies randomising 7837 women. No significant difference was shown
      in perinatal or infant mortality for infants of women allocated to any
      prophylactic antibiotics compared with no antibiotics. However, an increase in
      neonatal deaths was shown for infants of women receiving any prophylactic
      antibiotics when compared with placebo (RR 1.57, 95% CI 1.03 to 2.40; NNTH 149,
      95% CI 2500 to 61). No reduction in preterm birth or other clinically important
      short-term outcomes for the infant were shown.Long-term child outcomes to seven
      years of age were available for infants in the UK enrolled in the ORACLE II
      trial. Comparing any antibiotics with placebo, a marginally non-statistically
      significant increase was shown in any functional impairment (RR 1.10, 95% CI 0.99
      to 1.23) and cerebral palsy (CP) (RR 1.82, 95% CI 0.99 to 3.34). In subgroup
      analysis, CP was statistically significantly increased for infants of women
      allocated to macrolide and beta-lactam antibiotics combined compared with placebo
      (RR 2.83, 95% CI 1.02 to 7.88; NNTH 35, 95% CI 333 to 9).Further, exposure to any
      macrolide antibiotics (including erythromycin alone or erythromycin plus co
      amoxiclav) versus no macrolide antibiotics (including placebo and co-amoxiclav
      alone) was shown to increase neonatal death (RR 1.52, 95% CI 1.05 to 2.19; NNTH
      139, 95% CI 1429 to 61), any functional impairment (RR 1.11, 95% CI 1.01 to 1.20;
      NNTH 24, 95% CI 263 to 13) and CP (RR 1.90, 95% CI 1.20 to 3.01; NNTH 64, 95% CI
      286 to 29). Exposure to any beta-lactam (beta-lactam alone or in combination with
      macrolide antibiotics) versus no beta-lactam antibiotics resulted in more
      neonatal deaths (RR 1.51, 95% CI 1.06 to 2.15; NNTH 143, 95% CI 1250 to 63) and
      CP (RR 1.67, 95% CI 1.06 to 2.61; NNTH 79, 95% CI 909 to 33), however no
      difference was shown in functional impairment.Maternal infection was reduced with
      the use of any prophylactic antibiotics compared with placebo (RR 0.74, 95% CI
      0.63 to 0.86; NNTB 34, 95% CI 24 to 63) and any beta-lactam compared with no beta
      lactam antibiotics (RR 0.80, 95% CI 0.69 to 0.92; NNTB 47, 95% CI 31 to 119).
      However, caution should be exercised with this finding due to the possibility of
      bias shown by funnel plot asymmetry. Any beta-lactam compared with no beta-lactam
      antibiotics was associated with an increase in maternal adverse drug reaction (RR
      1.61, 95% CI 1.02 to 2.54; NNTH 17, 95% CI 526 to 7). AUTHORS' CONCLUSIONS: This
      review did not demonstrate any benefit in important neonatal outcomes with the
      use of prophylactic antibiotics for women in preterm labour with intact
      membranes, although maternal infection may be reduced. Of concern, is the finding
      of short- and longer-term harm for children of mothers exposed to antibiotics.
      The evidence supports not giving antibiotics routinely to women in preterm labour
      with intact membranes in the absence of overt signs of infection.Further research
      is required to develop sensitive markers of subclinical infection for women in
      preterm labour with intact membranes, as this is a group that might benefit from
      future novel interventions, including new modalities of antibiotic therapy. The
      results of this review demonstrate the need for future trials in the area of
      preterm birth to include assessment of long-term neurodevelopmental outcome.

PMID- 24307519
TI  - Enhanced osteoconductivity of sodium-substituted hydroxyapatite by system
      instability.
AB  - The effect of substituting sodium for calcium on enhanced osteoconductivity of
      hydroxyapatite was newly investigated. Sodium-substituted hydroxyapatite was
      synthesized by reacting calcium hydroxide and phosphoric acid with sodium nitrate
      followed by sintering. As a control, pure hydroxyapatite was prepared under
      identical conditions, but without the addition of sodium nitrate. Substitution of
      calcium with sodium in hydroxyapatite produced the structural vacancies for
      carbonate ion from phosphate site and hydrogen ion from hydroxide site of
      hydroxyapatite after sintering. The total system energy of sodium-substituted
      hydroxyapatite with structural defects calculated by ab initio methods based on
      quantum mechanics was much higher than that of hydroxyapatite, suggesting that
      the sodium-substituted hydroxyapatite was energetically less stable compared with
      hydroxyapatite. Indeed, sodium-substituted hydroxyapatite exhibited higher
      dissolution behavior of constituent elements of hydroxyapatite in simulated body
      fluid (SBF) and Tris-buffered deionized water compared with hydroxyapatite, which
      directly affected low-crystalline hydroxyl-carbonate apatite forming capacity by
      increasing the degree of apatite supersaturation in SBF. Actually, sodium
      substituted hydroxyapatite exhibited markedly improved low-crystalline hydroxyl
      carbonate apatite forming capacity in SBF and noticeably higher osteoconductivity
      4 weeks after implantation in calvarial defects of New Zealand white rabbits
      compared with hydroxyapatite. In addition, there were no statistically
      significant differences between hydroxyapatite and sodium-substituted
      hydroxyapatite on cytotoxicity as determined by BCA assay. Taken together, these
      results indicate that sodium-substituted hydroxyapatite with structural defects
      has promising potential for use as a bone grafting material due to its enhanced
      osteoconductivity compared with hydroxyapatite.

PMID- 24307521
TI  - Cytotoxicity and genotoxicity of triethyleneglycol-dimethacrylate in macrophages
      involved in DNA damage and caspases activation.
AB  - Triethyleneglycol-dimethacrylate (TEGDMA) is a monomer and widely used in dental
      composite resins. TEGDMA has been found to exhibit cytotoxicity and genotoxicity
      on many cells. However, little is known about the potential toxicological
      implications of TEGDMA on murine macrophage cell line RAW264.7. In this study,
      TEGDMA demonstrated a cytotoxic effect to RAW264.7 cells in a concentration- and
      time-dependent manner (p < 0.05). TEGDMA was found to induce two modes of cell
      death in a concentration-dependent manner (p < 0.05). TEGDMA-induced cell
      apoptosis was demonstrated by the increase in the portion of sub-G0/G1 phase and
      DNA ladder formation. In addition, TEGDMA exhibited genotoxicity via a dose
      related increase in the numbers of micronucleus and DNA strand breaks (p < 0.05).
      Furthermore, the activation of caspase-3, -8, and -9 were generated by TEGDMA in
      a dose-dependent manner (p < 0.05). These results indicated that cytotoxicity and
      genotoxicity induced by TEGDMA in macrophages may be via DNA damage and caspase
      activation.

PMID- 24307523
TI  - Ring-opening polymerization reactions of propylene oxide catalyzed by porphyrin
      metal 3+ complexes of aluminum, chromium and cobalt.
AB  - In today's world, a major scientific challenge is preserving the delicate balance
      between industrial growth and a pollutant free terrestrial environment. Thus,
      "greener" syntheses of commodity materials, capture and utilization of gaseous
      industrial by-products have become research areas of increasing significance. The
      pioneering work of Inoue showed a potential utilization of CO2, a major
      petrochemical by-product, and opened a new field of research. Inoue discovered
      the (porphyrin)Al(III)X catalyst systems, (X=Cl(-) or alkoxide) which
      copolymerize CO2 with epoxides to produce polycarbonates. This catalyst can also
      copolymerize epoxides and cyclic anhydrides to form polyesters. The current
      record describes our research aimed towards mechanistic understanding and further
      developments of (porphyrin)M(III)X catalyst systems. This detailed account shows
      the influence of the porphyrin ligands (tetraphenylporphyrin (TPP),
      octaethylporphyrin (OEP), tetrakis-pentafluorophenylporphyrin (TFPP)), metal
      centers (Al, Cr, and Co) and Lewis base co-catalysts on the individual reaction
      steps and equilibria involved in the copolymerization processes.

PMID- 24307522
TI  - Invertebrate specific D1-like dopamine receptor in control of salivary glands in
      the black-legged tick Ixodes scapularis.
AB  - The control of tick salivary secretion, which plays a crucial role in
      compromising the host immune system, involves complex neural mechanisms. Dopamine
      is known to be the most potent activator of salivary secretion, as a
      paracrine/autocrine factor. We describe the invertebrate-specific D1-like
      dopamine receptor (InvD1L), which is highly expressed in tick salivary glands.
      The InvD1L phylogenic clade was found only in invertebrates, suggesting that this
      receptor was lost in vertebrates during evolution. InvD1L expressed in Chinese
      hamster ovary (CHO)-K1 cells was activated by dopamine with a median effective
      dose (EC50 ) of 1.34 MUM. Immunohistochemistry using the antibody raised against
      InvD1L revealed two different types of immunoreactivities: basally located axon
      terminals that are colocalized with myoinhibitory peptide (MIP) and SIFamide
      neuropeptides, and longer axon-like processes that are positive only for the
      InvD1L antibody and extended to the apical parts of the acini. Both structures
      were closely associated with the myoepithelial cell, as visualized by beta
      tubulin antibody, lining the acinar lumen in a web-like fashion. Subcellular
      localizations of InvD1L in the salivary gland suggest that InvD1L modulates the
      neuronal activities including MIP/SIFamide varicosities, and leads the
      contraction of myoepithelial cells and/or of the acinar valve to control the
      efflux of the luminal content. Combining the previously described D1 receptor
      with its putative function for activating an influx of fluid through the
      epithelial cells of acini, we propose that complex control of the tick salivary
      glands is mediated through two different dopamine receptors, D1 and InvD1L, for
      different downstream responses of the acinar cells.

PMID- 24307524
TI  - Direct evidence for intermolecular oxidative addition of sigma(Si-Si) bonds to
      gold.
AB  - Oxidative addition plays a major role in transition-metal catalysis, but this
      elementary step remains very elusive in gold chemistry. It is now revealed that
      in the presence of GaCl3, phosphine gold chlorides promote the oxidative addition
      of disilanes at low temperature. The ensuing bis(silyl) gold(III) complexes were
      characterized by quantitative (31)P and (29)Si NMR spectroscopy. Their structures
      (distorted Y shape) and the reaction profile of sigma(Si-Si) bond activation were
      analyzed by DFT calculations. These results provide evidence for the
      intermolecular oxidative addition of sigma(Si-Si) bonds to gold and open
      promising perspectives for the development of new gold-catalyzed redox
      transformations.

PMID- 24307526
TI  - It is all in the face: carotenoid skin coloration loses attractiveness outside
      the face.
AB  - Recently, the importance of skin colour for facial attractiveness has been
      recognized. In particular, dietary carotenoid-induced skin colour has been
      proposed as a signal of health and therefore attractiveness. While perceptual
      results are highly consistent, it is currently not clear whether carotenoid skin
      colour is preferred because it poses a cue to current health condition in humans
      or whether it is simply seen as a more aesthetically pleasing colour,
      independently of skin-specific signalling properties. Here, we tested this
      question by comparing attractiveness ratings of faces to corresponding ratings of
      meaningless scrambled face images matching the colours and contrasts found in the
      face. We produced sets of face and non-face stimuli with either healthy (high
      carotenoid coloration) or unhealthy (low-carotenoid coloration) colour and asked
      participants for attractiveness ratings. Results showed that, while for faces
      increased carotenoid coloration significantly improved attractiveness, there was
      no equivalent effect on perception of scrambled images. These findings are
      consistent with a specific signalling system of current condition through skin
      coloration in humans and indicate that preferences are not caused by sensory
      biases in observers. 

PMID- 24307525
TI  - Mesenchymal stem/stromal cells inhibit the NLRP3 inflammasome by decreasing
      mitochondrial reactive oxygen species.
AB  - Mesenchymal stem/stromal cells (MSCs) control excessive inflammatory responses by
      modulating a variety of immune cells including monocytes/macrophages. However,
      the mechanisms by which MSCs regulate monocytes/macrophages are unclear.
      Inflammasomes in macrophages are activated upon cellular "danger" signals and
      initiate inflammatory responses through the maturation and secretion of
      proinflammatory cytokines such as interleukin 1beta (IL-1beta). Here we
      demonstrate that human MSCs (hMSCs) negatively regulate NLRP3 inflammasome
      activation in human or mouse macrophages stimulated with LPS and ATP. Caspase-1
      activation and subsequent IL-1beta release were decreased in macrophages by
      direct or transwell coculture with hMSCs. Addition of hMSCs to macrophages either
      at a LPS priming or at a subsequent ATP step similarly inhibited the inflammasome
      activation. The hMSCs had no effect on NLRP3 and IL-1beta expression at mRNA
      levels during LPS priming. However, MSCs markedly suppressed the generation of
      mitochondrial reactive oxygen species (ROS) in macrophages. Further analysis
      showed that NLRP3-activated macrophages stimulated hMSCs to increase the
      expression and secretion of stanniocalcin (STC)-1, an antiapoptotic protein.
      Addition of recombinant protein STC-1 reproduced the effects of hMSCs in
      inhibiting NLRP3 inflammasome activation and ROS production in macrophages.
      Conversely, the effects of hMSCs on macrophages were largely abrogated by an
      small interfering RNA (siRNA) knockdown of STC-1. Together, our results reveal
      that hMSCs inhibit NLRP3 inflammasome activation in macrophages primarily by
      secreting STC-1 in response to activated macrophages and thus by decreasing
      mitochondrial ROS.

PMID- 24307527
TI  - The evolution of cerebellum structure correlates with nest complexity.
AB  - Across the brains of different bird species, the cerebellum varies greatly in the
      amount of surface folding (foliation). The degree of cerebellar foliation is
      thought to correlate positively with the processing capacity of the cerebellum,
      supporting complex motor abilities, particularly manipulative skills. Here, we
      tested this hypothesis by investigating the relationship between cerebellar
      foliation and species-typical nest structure in birds. Increasing complexity of
      nest structure is a measure of a bird's ability to manipulate nesting material
      into the required shape. Consistent with our hypothesis, avian cerebellar
      foliation increases as the complexity of the nest built increases, setting the
      scene for the exploration of nest building at the neural level. 

PMID- 24307528
TI  - Male-male competition leads to less abundant but more attractive sperm.
AB  - Males employ complex strategies to optimize their reproductive success when faced
      with male-male competition; for instance, they can adjust the ejaculate
      characteristics. In copulating species, a male may also strategically adjust his
      ejaculate expenditure according to female quality. Quantifying the relative
      contribution of ejaculate plasticity in male reproductive success is often
      difficult, especially when females exert postcopulatory cryptic choice. One way
      to quantify the functional significance of ejaculate plasticity is offered by
      mating systems in which the reproductive partners do not meet each other during
      insemination. In the collembolan Orchesella cincta, males deposit their
      ejaculates (spermatophores) irrespective of the presence of females. We tested
      whether Orchesella males adjust spermatophore number when exposed to the presence
      of another male and whether changes in spermatophore production influence female
      choice. We found that Orchesella males display plasticity in spermatophore
      allocation. Males decreased the spermatophore number when exposed to a rival
      male. Moreover, females preferentially took up spermatophores of males that were
      exposed to a competitor. The reduction in spermatophore number suggests, besides
      an adaptive response to the risk of ejaculate removal by rival males, an
      optimization strategy owing to the costs of more attractive spermatophores. 

PMID- 24307529
TI  - Motion dazzle: a locust's eye view.
AB  - Motion dazzle describes high-contrast patterns (e.g. zigzags on snakes and dazzle
      paint on World War I ships) that do not conceal an object, but inhibit an
      observer's perception of its motion. However, there is limited evidence for this
      phenomenon. Locusts have a pair of descending contralateral movement detector
      (DCMD) neurons which respond to predator-like looming objects and trigger escape
      responses. Within the network providing input to a DCMD, separate channels are
      excited when moving edges cause areas of the visual field to brighten or darken,
      respectively, and these stimuli interact antagonistically. When a looming square
      has an upper half and lower half that are both darker than background, it elicits
      a stronger DCMD response than the upper half does alone. However, when a looming
      square has a darker-than-background upper half and a brighter-than-background
      lower half, it elicits a weaker DCMD response than its upper half does alone.
      This effect allows high-contrast patterns to weaken and delay DCMD response
      parameters implicated in escape decisions, and is analogous to motion dazzle.
      However, the motion dazzle effect does not provide the best means of motion
      camouflage, because uniform bright squares, or low-contrast squares, elicit
      weaker DCMD responses than high-contrast, half dark, half bright squares. 

PMID- 24307530
TI  - Ignoring discards biases the assessment of fisheries' ecological fingerprint.
AB  - Understanding the pressures of fisheries on the ecosystem is crucial for
      effective management. Fishery removals, or catch, are composed of both landings
      and discards. However, the use of discards data in studies investigating the
      effect of the fishing pressures is sparse. Here, we explore the individual
      contribution of both these catch components to the overall pressure of fisheries
      on the ecosystem metrics. Using Irish observer data, we compare the linear
      relationship between several ecological metrics calculated for landings and
      discards with those of catch. Our results show that in fisheries with high
      discarding rates, discards can drive the fisheries' ecological fingerprint and
      highlight the need to rectify landings-based estimates to make them
      representative of those of catch in order to gain a robust picture of the impact
      of fisheries. 

PMID- 24307531
TI  - Rates of transposition in Escherichia coli.
AB  - The evolutionary role of transposable elements (TEs) is still highly
      controversial. Two key parameters, the transposition rate (u and w, for
      replicative and non-replicative transposition) and the excision rate (e) are
      fundamental to understanding their evolution and maintenance in populations. We
      have estimated u, w and e for six families of TEs (including eight members: IS1,
      IS2, IS3, IS4, IS5, IS30, IS150 and IS186) in Escherichia coli, using a mutation
      accumulation (MA) experiment. In this experiment, mutations accumulate
      essentially at the rate at which they appear, during a period of 80 500 (1610
      generations * 50 lines) generations, and spontaneous transposition events can be
      detected. This differs from other experiments in which insertions accumulated
      under strong selective pressure or over a limited genomic target. We therefore
      provide new estimates for the spontaneous rates of transposition and excision in
      E. coli. We observed 25 transposition and three excision events in 50 MA lines,
      leading to overall rate estimates of u ~ 1.15 * 10(-5), w ~ 4 * 10(-8) and e ~
      1.08 * 10(-6) (per element, per generation). Furthermore, extensive variation
      between elements was found, consistent with previous knowledge of the mechanisms
      and regulation of transposition for the different elements. 

PMID- 24307532
TI  - Synthesis of a new fluorine-18 glycosylated 'click' cyanoquinoline for the
      imaging of epidermal growth factor receptor.
AB  - This study reports the radiosynthesis of a new fluorine-18 glycosylated 'click'
      cyanoquinoline [(18) F]5 for positron emission tomography imaging of epidermal
      growth factor receptor (EGFR). The tracer was obtained in 47.7 +/- 7.5% (n = 3)
      decay-corrected radiochemical yield from 2-[(18) F]fluoro-2-deoxy-beta-d
      glucopyranosyl azide, and the overall nondecay-corrected radiochemical yield from
      aqueous fluoride was 8.6 +/- 2.3% (n = 3). An in vitro preliminary cellular
      uptake study showed selectivity of the tracer for EGFR-positive A431 cell lines
      versus EGFR-negative MCF-7 cell lines. [(18) F]5 tracer uptake in A431 cells was
      significantly reduced by addition of the cold isotope analogue compound 5.

PMID- 24307533
TI  - Comment on "On gestational weeks and maths".

PMID- 24307534
TI  - Response to "On gestational weeks and maths".

PMID- 24307535
TI  - Aerobic oxidative coupling of resveratrol and its analogues by visible light
      using mesoporous graphitic carbon nitride (mpg-C(3)N(4)) as a bioinspired
      catalyst.
AB  - The first aerobic oxidative coupling of resveratrol and its analogues by
      mesoporous graphitic carbon nitride as a bioinspired catalyst with visible light
      has been developed. With this method, delta-viniferin and its analogues were
      synthesized in moderate to high yield. The metal-free conditions, visible-light
      irradiation, and the ideal oxidant, molecular oxygen, make this coupling reaction
      environmental friendly and practical. 

PMID- 24307536
TI  - Japanese postmarketing surveillance of clopidogrel for patients with non-ST
      segment-elevation acute coronary syndrome indicated for percutaneous coronary
      intervention (J-PLACE NSTE-ACS).
AB  - Clopidogrel in combination with aspirin has been a standard therapy for patients
      who have undergone percutaneous coronary intervention. The present study was
      conducted as a postmarketing surveillance, for the purpose of assessing the
      safety and efficacy of clopidogrel in real clinical practice in patients with non
      ST-segment-elevation acute coronary syndrome (NSTE-ACS). Subjects were registered
      between March 2008 and December 2010, and as a result, patients not only with
      NSTE-ACS but also other types of ischemic heart diseases were enrolled. Data on
      off-label subjects were used only in safety evaluation. After excluding patients
      with inappropriate clinical report forms, 3,673 patients with non-ST-segment
      elevation myocardial infarction, unstable angina, STEMI, stable angina, or old
      myocardial infarction were observed for safety evaluation. Efficacy was assessed
      in 2,562 of the 3,673 patients with NSTE-ACS. Aspirin was concomitantly
      prescribed to 3,615/3,673 (98.6 %) of the safety group, and 2,374/3,673 (64.6 %)
      received a loading dose of clopidogrel. During a maximum follow-up period of 12
      months, 397 (10.8 %) of the 3,673 patients experienced adverse drug reactions
      (ADRs), of whom 145 (4.0 %) had serious conditions, as classified by the
      investigators. The most frequently observed ADRs were hepatobiliary and
      gastrointestinal disorders. Bleeding adverse events were observed in 138 patients
      (3.8 %) and 80 cases (2.2 %) were considered as serious. The 1-year cumulative
      incidence of major adverse cardiovascular events and major adverse cardiac and
      cerebrovascular events in the patients with NSTE-ACS were estimated to be 11.6
      and 12.2 %, respectively. Serious AEs that substantially affect the safety
      profile of clopidogrel were not confirmed.

PMID- 24307537
TI  - "Primary" percutaneous transluminal renal angioplasty for late stent thrombosis.
AB  - Renal artery thrombosis is a rare, but serious and often misdiagnosed, condition,
      with poor prognosis and renal functional impairment. As for the rarity of the
      occurrence, data about real incidence of renal stent thrombosis are lacking,
      ranging from 0 to 1 % depending on the study evaluated. We report the case of a
      43-year-old man with nephrovascular hypertension, previously treated with renal
      stent implantation, with a late stent thrombosis. The diagnostic and subsequent
      therapeutic management was analyzed and discussed. 

PMID- 24307538
TI  - Whole-body MRI, including diffusion-weighted imaging, for staging lymphoma:
      comparison with CT in a prospective multicenter study.
AB  - PURPOSE: To compare whole-body magnetic resonance imaging (MRI), including
      diffusion-weighted imaging (DWI), to computed tomography (CT) for staging newly
      diagnosed lymphoma. MATERIALS AND METHODS: In all, 108 patients with newly
      diagnosed lymphoma prospectively underwent whole-body MRI (T1-weighted and T2
      weighted short inversion time inversion recovery [n = 108], and DWI [n = 104])
      and CT. Ann Arbor stages were assigned according to whole-body MRI and CT
      findings. Staging disagreements were resolved using bone marrow biopsy, FDG-PET,
      and follow-up studies. The results were descriptively analyzed. RESULTS: Staging
      results of whole-body MRI without DWI were equal to those of CT in 66.6%, higher
      in 24.1%, and lower in 9.3%, with correct/incorrect/unresolved higher staging and
      incorrect/unresolved lower staging relative to CT in 15/7/4 and 9/1 patient(s),
      respectively. Staging results of whole-body MRI with DWI were equal to those of
      CT in 65.4%, higher in 27.9%, and lower in 6.7%, with
      correct/incorrect/unresolved higher staging and incorrect/unresolved lower
      staging relative to CT in 18/6/5 and 6/1 patient(s), respectively. CONCLUSION:
      The results of this study suggest that whole-body MRI staging equals CT staging
      in the majority of patients with newly diagnosed lymphoma. No advantage of
      additional DWI was demonstrated. Whole-body MRI can be a good alternative to CT
      if radiation exposure should be avoided.

PMID- 24307520
TI  - Purinergic signalling in the gastrointestinal tract and related organs in health
      and disease.
AB  - Purinergic signalling plays major roles in the physiology and pathophysiology of
      digestive organs. Adenosine 5'-triphosphate (ATP), together with nitric oxide and
      vasoactive intestinal peptide, is a cotransmitter in non-adrenergic, non
      cholinergic inhibitory neuromuscular transmission. P2X and P2Y receptors are
      widely expressed in myenteric and submucous enteric plexuses and participate in
      sympathetic transmission and neuromodulation involved in enteric reflex
      activities, as well as influencing gastric and intestinal epithelial secretion
      and vascular activities. Involvement of purinergic signalling has been identified
      in a variety of diseases, including inflammatory bowel disease, ischaemia,
      diabetes and cancer. Purinergic mechanosensory transduction forms the basis of
      enteric nociception, where ATP released from mucosal epithelial cells by
      distension activates nociceptive subepithelial primary afferent sensory fibres
      expressing P2X3 receptors to send messages to the pain centres in the central
      nervous system via interneurons in the spinal cord. Purinergic signalling is also
      involved in salivary gland and bile duct secretion. 

PMID- 24307539
TI  - Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: an
      economic evaluation alongside a randomised controlled trial.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of the
      lungs of unknown origin with a poor prognosis. A small trial of co-trimoxazole
      demonstrated improvements in symptoms and functional parameters over a 3-month
      period. We therefore conducted a larger trial with a concurrent economic
      evaluation to investigate this antibiotic further. METHODS: We report an economic
      evaluation alongside a multi-centre, randomised, placebo-controlled, double-blind
      trial of 12 months therapy with 960 mg co-trimoxazole daily in 181 patients with
      fibrotic idiopathic interstitial pneumonia (IIP). Patients were recruited from 28
      university and district hospitals in the UK and were aged over 40 years with
      fibrotic IIP. We report costs to the National Health Service (NHS) and society,
      change in forced vital capacity (primary endpoint) and quality-adjusted life
      years (QALYs) gained, incremental cost effectiveness and cost utility ratios over
      12 months. RESULTS: From the perspective of society, mean cost per patient in the
      co-trimoxazole arm was approximately L1177 higher than in the placebo arm, but
      mean QALYs were 0.053 higher yielding an incremental cost-effectiveness ratio of
      L22,012 per QALY gained with a 54.44 % probability of being below L30,000. The
      cost of IPF to UK society in 2011 is tentatively estimated at L124 million, of
      which 13 % is NHS costs, 1 % social services, 2 % patient out-of-pocket costs and
      84 % lost productivity. CONCLUSIONS: Given commonly employed thresholds in the UK
      NHS, on balance co-trimoxazole may be a cost-effective treatment for IPF,
      although there is substantial decision uncertainty. However, recent guidance on
      the use of immunosuppressive therapy in IPF patients should be taken into account
      prior to any policy decision.

PMID- 24307540
TI  - The nasal cycle during wakefulness and sleep and its relation to body position.
AB  - OBJECTIVES/HYPOTHESIS: To compare the occurrence, duration, and relative
      amplitudes of the nasal cycle (NC) during wakefulness and sleep, and to
      investigate the relationship of the NC to body position. STUDY DESIGN/METHODS: In
      20 healthy subjects, the NC was measured by long-term rhinoflowmetry for an
      average 23.1 hours during wakefulness and sleep. Head and body position were also
      recorded during the night. RESULTS: A classic NC was displayed by 50% of subjects
      during wakefulness and by 75% of the subjects during sleep. Cycle duration during
      wakefulness was 91.1 minutes (+/- 65.2; 20-337), increasing significantly during
      sleep to 178 minutes (+/- 92.8; 21-498) (P < 0.01). The relative mean flow of the
      working phase during wakefulness was 67.6% (+/- 8.0; 58-90), and it was
      significantly higher during sleep at 82.0% (+/- 6.8; 63-93) (P < 0.01). On
      recumbency, there was a significant correlation between body position and resting
      phase side (r = 0.67; P = 0.024). To a significant extent, positional shifts led
      to subsequent NC laterality changes (22%; P < 0.01). Conversely, to a significant
      extent, positional shifts preceded NC laterality changes (57.6%; P < 0.01). Body
      position changed in a nonsignificant number of cases (30.3%; P = 0.16) due to
      reversal of the congestion side of the inferior turbinates. CONCLUSION: The
      results of our study show that the NC during sleep is characterized by longer
      cycle durations and greater amplitudes than during wakefulness on normal physical
      activity. Shifts in body position during sleep alter the NC in a specific
      direction to a significant extent, but the opposite is not the case. LEVEL OF
      EVIDENCE: 4.

PMID- 24307541
TI  - Diagnostic criteria for pancreaticobiliary maljunction 2013.
AB  - Pancreaticobiliary maljunction is a congenital malformation in which the
      pancreatic and bile ducts join anatomically outside the duodenal wall. The
      diagnostic criteria for pancreaticobiliary maljunction were proposed in 1987. The
      committee of The Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM)
      for diagnostic criteria for pancreaticobiliary maljunction began to revise the
      diagnostic criteria from 2011 taking recently advanced diagnostic imaging
      techniques into consideration, and the final revised version was approved in the
      36(th) Annual Meeting of JSPBM. For diagnosis of pancreaticobiliary maljunction,
      an abnormally long common channel and/or an abnormal union between the pancreatic
      and bile ducts must be evident on direct cholangiography, such as endoscopic
      retrograde cholangiopancreatography, percutaneous transpehatic cholangiography,
      or intraoperative cholangiography; magnetic resonance cholangiopancreatography;
      or three-dimensional drip infusion cholangiography computed tomography. However,
      in cases with a relatively short common channel, it is necessary to confirm that
      the effect of the papillary sphincter does not extend to the junction by direct
      cholangiography. Pancreaticobiliary maljunction can be diagnosed also by
      endoscopic ultrasonography or multi-planar reconstruction images provided by
      multi-detector row computed tomography. Elevated amylase levels in bile and
      extrahepatic bile duct dilatation strongly suggest the existence of
      pancreaticobiliary maljunction.

PMID- 24307542
TI  - Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical
      proliferative) tumours and associated peritoneal implants.
AB  - There is debate as to whether peritoneal implants associated with serous
      borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary
      are derived from the primary ovarian tumour or arise independently in the
      peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease
      identified from a nation-wide tumour registry in Denmark. Mutational analysis for
      hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS
      mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis
      was successful in 56 peritoneal implants and revealed KRAS mutations in 34
      (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be
      performed in two primary tumours and in nine implants, either because DNA
      amplification failed or because there was insufficient tissue for mutational
      analysis. For these specimens we performed VE1 immunohistochemistry, which was
      shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation.
      VE1 staining was positive in one of two APSTs and seven of nine implants. Thus,
      among 63 implants for which mutation status was known (either by direct
      mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS
      mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were
      found in 34 (91%) of 37 SBT/APST-implant pairs and identical BRAF mutations in 14
      (100%) of 14 SBT/APST-implant pairs. Wild-type KRAS and BRAF (at the loci
      investigated) were found in 11 (100%) of 11 SBT/APST-implant pairs. Overall
      concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST-implant (non
      invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence
      that the vast majority of peritoneal implants, non-invasive and invasive, harbour
      the identical KRAS or BRAF mutations that are present in the associated SBT/APST,
      supporting the view that peritoneal implants are derived from the primary ovarian
      tumour.

PMID- 24307543
TI  - Prognostic implication of HSPA (HSP70) in breast cancer patients treated with
      neoadjuvant anthracycline-based chemotherapy.
AB  - Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer
      to reduce tumor size before surgery. Unfortunately, resistance to chemotherapy
      may arise from a variety of mechanisms. Heat shock proteins (HSPs), which are
      highly expressed in mammary tumor cells, have been implicated in anticancer drug
      resistance. In spite of the widely described value of HSPs as molecular markers
      in cancer, their implications in breast tumors treated with anthracycline-based
      neoadjuvant chemotherapy has been poorly explored. In this study, we have
      evaluated, by immunohistochemistry, the expression of HSP27 (HSPB1) and HSP70
      (HSPA) in serial biopsies from locally advanced breast cancer patients (n = 60)
      treated with doxorubicin (DOX)- or epirubicin (EPI)-based monochemotherapy.
      Serial biopsies were taken at days 1, 3, 7, and 21, and compared with
      prechemotherapy and surgical biopsies. After surgery, the patients received
      additional chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil.
      High nuclear HSPB1 and HSPA expressions were found in invasive cells after
      DOX/EPI administration (P < 0.001), but the drug did not affect the cytoplasmic
      expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P <
      0.01) levels at postchemotherapy. No correlations were found between HSPs
      expression and the clinical and pathological response to neoadjuvant therapy.
      However, in postchemotherapy biopsies, high nuclear (>31 % of the cells) and
      cytoplasmic HSPA expressions (>11 % of the tumor cells) were associated with
      better DFS (P = 0.0348 and P = 0.0118, respectively). We conclude that HSPA
      expression may be a useful prognostic marker in breast cancer patients treated
      with neoadjuvant DOX/EPI chemotherapy indicating the need to change the
      administered drugs after surgery for overcoming drug resistance. 

PMID- 24307544
TI  - Imaging tumour ATB0,+ transport activity by PET with the cationic amino acid O
      2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine.
AB  - PURPOSE: The concentrative amino acid transporter ATB(0,+) (SLC6A14) is under
      evaluation as a target for anticancer therapy. An ATB(0,+)-selective positron
      emission tomography (PET) probe could advance preclinical drug development. We
      characterised the cationic tyrosine analogue O-2((2-[(18)F]fluoroethyl)methyl
      amino)ethyltyrosine ([(18)F]FEMAET) as a PET probe for ATB(0,+) activity.
      PROCEDURES: Cell uptake was studied in vitro. ATB(0,+) expression was quantified
      by real-time PCR. [(18)F]FEMAET accumulation in xenografts was investigated by
      small animal PET with mice. RESULTS: [(18)F]FEMAET accumulated in PC-3 and NCI
      H69 cancer cells in vitro. As expected for ATB(0,+) transport, uptake was
      inhibited by LAT/ATB(0,+) inhibitors and dibasic amino acids, and [(18)F]FEMAET
      efflux was only moderately stimulated by extracellular amino acids. ATB(0,+) was
      expressed in PC-3 and NCI-H69 but not MDA-MB-231 xenografts. PET revealed
      accumulation in PC-3 and NCI-H69 xenografts and significant reduction by ATB(0,+)
      inhibition. Uptake was negligible in MDA-MB-231 xenografts. CONCLUSION: ATB(0,+)
      activity can be imaged in vivo by PET with [(18)F]FEMAET.

PMID- 24307545
TI  - Module assembly for designing multivalent mid-sized inhibitors of protein-protein
      interactions.
AB  - Developing clinically relevant synthetic agents that are capable of disrupting
      protein-protein interactions (PPIs) is now a major goal of scientific research.
      In an effort to explore new methodologies that are applicable to the design of
      synthetic PPI inhibitors, we examined a strategy based on the assembly of small
      module compounds to create multivalent mid-sized agents. This personal account
      describes three particular approaches based on module assembly: metal-chelating
      based ligand assembly, covalent chemical ligation templated by a targeted
      protein, and bivalent inhibitor design for simultaneous targeting of the active
      pocket and protein surface. These strategies were shown to be useful for
      synthesizing minimally sized synthetic agents for targeting PPIs and may enable
      development of agents that are applicable to inhibition of intracellular PPIs. 

PMID- 24307546
TI  - Copper-catalyzed reduction of alkyl triflates and iodides: an efficient method
      for the deoxygenation of primary and secondary alcohols.
AB  - We describe an effective method for catalytic reduction of 1 degrees  alkyl
      sulfonates, and 1 degrees  and 2 degrees  iodides in the presence of a wide range
      of functional groups. This Cu-catalyzed reaction provides a means for the
      effective deoxygenation of alcohols, as demonstrated by the highly selective
      reduction of 1 degrees  alcohols using a triflation/reduction sequence. A
      preliminary study of the reaction mechanism suggests that the reduction does not
      involve free-radical intermediates. 

PMID- 24307550
TI  - alpha,beta-Unsaturated acyl cyanides as new bis-electrophiles for
      enantioselective organocatalyzed formal [3+3]spiroannulation.
AB  - alpha,beta-Unsaturated acyl cyanides are key bis-electrophile substrates for
      successful domino enantioselective organocatalyzed Michael-intramolecular
      acylation domino sequences. This new reactivity has been applied to the synthesis
      of enantioenriched azaspiro[4,5]decanone ring systems by a formal
      [3+3]spiroannulation, constituting a rare example of synthesis of glutarimides in
      an optically active form. 

PMID- 24307551
TI  - Amplification and thrifty single-molecule sequencing of recurrent somatic
      structural variations.
AB  - Deletion of tumor-suppressor genes as well as other genomic rearrangements
      pervade cancer genomes across numerous types of solid tumor and hematologic
      malignancies. However, even for a specific rearrangement, the breakpoints may
      vary between individuals, such as the recurrent CDKN2A deletion. Characterizing
      the exact breakpoints for structural variants (SVs) is useful for designating
      patient-specific tumor biomarkers. We propose AmBre (Amplification of
      Breakpoints), a method to target SV breakpoints occurring in samples composed of
      heterogeneous tumor and germline DNA. Additionally, AmBre validates SVs called by
      whole-exome/genome sequencing and hybridization arrays. AmBre involves a PCR
      based approach to amplify the DNA segment containing an SV's breakpoint and then
      confirms breakpoints using sequencing by Pacific Biosciences RS. To amplify
      breakpoints with PCR, primers tiling specified target regions are carefully
      selected with a simulated annealing algorithm to minimize off-target
      amplification and maximize efficiency at capturing all possible breakpoints
      within the target regions. To confirm correct amplification and obtain
      breakpoints, PCR amplicons are combined without barcoding and simultaneously long
      read sequenced using a single SMRT cell. Our algorithm efficiently separates
      reads based on breakpoints. Each read group supporting the same breakpoint
      corresponds with an amplicon and a consensus amplicon sequence is called. AmBre
      was used to discover CDKN2A deletion breakpoints in cancer cell lines: A549, CEM,
      Detroit562, MOLT4, MCF7, and T98G. Also, we successfully assayed RUNX1-RUNX1T1
      reciprocal translocations by finding both breakpoints in the Kasumi-1 cell line.
      AmBre successfully targets SVs where DNA harboring the breakpoints are present in
      1:1000 mixtures. 

PMID- 24307552
TI  - TIGRA: a targeted iterative graph routing assembler for breakpoint assembly.
AB  - Recent progress in next-generation sequencing has greatly facilitated our study
      of genomic structural variation. Unlike single nucleotide variants and small
      indels, many structural variants have not been completely characterized at
      nucleotide resolution. Deriving the complete sequences underlying such
      breakpoints is crucial for not only accurate discovery, but also for the
      functional characterization of altered alleles. However, our current ability to
      determine such breakpoint sequences is limited because of challenges in aligning
      and assembling short reads. To address this issue, we developed a targeted
      iterative graph routing assembler, TIGRA, which implements a set of novel data
      analysis routines to achieve effective breakpoint assembly from next-generation
      sequencing data. In our assessment using data from the 1000 Genomes Project,
      TIGRA was able to accurately assemble the majority of deletion and mobile element
      insertion breakpoints, with a substantively better success rate and accuracy than
      other algorithms. TIGRA has been applied in the 1000 Genomes Project and other
      projects and is freely available for academic use. 

PMID- 24307554
TI  - Endothelial, epithelial, and fibroblast cells exhibit specific splicing programs
      independently of their tissue of origin.
AB  - Alternative splicing is the main mechanism of increasing the proteome diversity
      coded by a limited number of genes. It is well established that different tissues
      or organs express different splicing variants. However, organs are composed of
      common major cell types, including fibroblasts, epithelial, and endothelial
      cells. By analyzing large-scale data sets generated by The ENCODE Project
      Consortium and after extensive RT-PCR validation, we demonstrate that each of the
      three major cell types expresses a specific splicing program independently of its
      organ origin. Furthermore, by analyzing splicing factor expression across
      samples, publicly available splicing factor binding site data sets (CLIP-seq),
      and exon array data sets after splicing factor depletion, we identified several
      splicing factors, including ESRP1 and 2, MBNL1, NOVA1, PTBP1, and RBFOX2, that
      contribute to establishing these cell type-specific splicing programs. All of the
      analyzed data sets are freely available in a user-friendly web interface named
      FasterDB, which describes all known splicing variants of human and mouse genes
      and their splicing patterns across several dozens of normal and cancer cells as
      well as across tissues. Information regarding splicing factors that potentially
      contribute to individual exon regulation is also provided via a dedicated CLIP
      seq and exon array data visualization interface. To the best of our knowledge,
      FasterDB is the first database integrating such a variety of large-scale data
      sets to enable functional genomics analyses at exon-level resolution. 

PMID- 24307553
TI  - Regulatory modules controlling maize inflorescence architecture.
AB  - Genetic control of branching is a primary determinant of yield, regulating seed
      number and harvesting ability, yet little is known about the molecular networks
      that shape grain-bearing inflorescences of cereal crops. Here, we used the maize
      (Zea mays) inflorescence to investigate gene networks that modulate determinacy,
      specifically the decision to allow branch growth. We characterized developmental
      transitions by associating spatiotemporal expression profiles with morphological
      changes resulting from genetic perturbations that disrupt steps in a pathway
      controlling branching. Developmental dynamics of genes targeted in vivo by the
      transcription factor RAMOSA1, a key regulator of determinacy, revealed potential
      mechanisms for repressing branches in distinct stem cell populations, including
      interactions with KNOTTED1, a master regulator of stem cell maintenance. Our
      results uncover discrete developmental modules that function in determining grass
      specific morphology and provide a basis for targeted crop improvement and
      translation to other cereal crops with comparable inflorescence architectures. 

PMID- 24307556
TI  - Spermicide used alone for contraception.
AB  - BACKGROUND: Spermicides have been used as contraceptives for thousands of years.
      Despite this long use, only recently have studies examined the comparative
      efficacy and acceptability of these vaginal medications. Spermicides contain an
      active ingredient (most commonly nonoxynol-9) and a formulation used to disperse
      the product, such as foam or vaginal suppository. OBJECTIVES: This review
      examined all known randomized controlled trials of a spermicide used alone for
      contraception. SEARCH METHODS: In August 2013, we searched the following
      computerized databases for randomized controlled trials of spermicides for
      contraception: CENTRAL, MEDLINE, POPLINE, LILACS, EMBASE, ClinicalTrials.gov, and
      ICTRP. For the initial review, we examined the reference lists of trials found as
      well as those of review articles and textbook chapters. SELECTION CRITERIA: We
      included any trial of a commercial product used alone for contraception. Each
      included trial must have provided sufficient information to determine pregnancy
      rates. DATA COLLECTION AND ANALYSIS: Two authors independently extracted
      information from the trials identified. We did not conduct a meta-analysis, since
      most trials had large losses to follow up. We entered the data into tables and
      presented the results descriptively. MAIN RESULTS: We located reports from 14
      trials for the initial review, but have not identified any new trials since then.
      In the largest trial to date, the gel (Advantage S) containing the lowest dose of
      nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy
      than were gels with higher doses of the same agent (100 mg and 150 mg).
      Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for
      the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three
      different vehicles with 100 mg of nonoxynol-9 had similar efficacy.
      Interpretation of these figures is limited, since 39% of participants
      discontinued the method or were lost from the trial. Few important differences in
      efficacy emerged in other trials. AUTHORS' CONCLUSIONS: The probability of
      pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg
      was inferior to two other products tested in the largest trial. Aside from this
      finding, personal characteristics and behavior of users may be more important
      than characteristics of the spermicide products in determining the probability of
      pregnancy. Gel was liked more than the film or vaginal suppository in the largest
      trial. Spermicide trials have the dual challenges of difficult recruitment and
      high discontinuation rates; the latter threatens trial validity.

PMID- 24307555
TI  - CD13 regulates anchorage and differentiation of the skeletal muscle satellite
      stem cell population in ischemic injury.
AB  - CD13 is a multifunctional cell surface molecule that regulates inflammatory and
      angiogenic mechanisms in vitro, but its contribution to these processes in vivo
      or potential roles in stem cell biology remains unexplored. We investigated the
      impact of loss of CD13 on a model of ischemic skeletal muscle injury that
      involves angiogenesis, inflammation, and stem cell mobilization. Consistent with
      its role as an inflammatory adhesion molecule, lack of CD13 altered myeloid
      trafficking in the injured muscle, resulting in cytokine profiles skewed toward a
      prohealing environment. Despite this healing-favorable context, CD13(KO) animals
      showed significantly impaired limb perfusion with increased necrosis, fibrosis,
      and lipid accumulation. Capillary density was correspondingly decreased,
      implicating CD13 in skeletal muscle angiogenesis. The number of CD45-/Sca1
      /alpha7-integrin+/beta1-integrin+ satellite cells was markedly diminished in
      injured CD13(KO) muscles and adhesion of isolated CD13(KO) satellite cells was
      impaired while their differentiation was accelerated. Bone marrow transplantation
      studies showed contributions from both host and donor cells to wound healing.
      Importantly, CD13 was coexpressed with Pax7 on isolated muscle-resident satellite
      cells. Finally, phosphorylated-focal adhesion kinase and ERK levels were reduced
      in injured CD13(KO) muscles, consistent with CD13 regulating satellite cell
      adhesion, potentially contributing to the maintenance and renewal of the
      satellite stem cell pool and facilitating skeletal muscle regeneration.

PMID- 24307557
TI  - The integration of cancer survivorship training in the curriculum of
      hematology/oncology fellows and radiation oncology residents.
AB  - BACKGROUND: Cancer specialists require an understanding of survivors' needs to
      insure optimal delivery of care. Training programs currently focus on treatment,
      while survivorship care focuses on time after treatment. Cancer survivorship
      training represents an education paradigm shift. METHODS: The Cancer Survivorship
      Workshop was held at the James P. Wilmot Cancer Center of the University of
      Rochester in academic year 2011-2012, with six sessions held. Objectives included
      the following: learning about survivorship from patient, primary care physician,
      and oncologist perspectives using a curriculum based on survivorship literature;
      designing treatment summaries (TSs) and survivorship care plans (SCPs) for five
      malignancies (lung, breast, prostate, colon, and lymphoma); and establishing
      collaboration between hematology/oncology (HO) and radiation oncology (RO)
      trainees by working together in teams. Course impact was assessed pre- and post
      training using a 13-question survey. Questions were answered using a 10-point
      scale, with predefined rating for each question. RESULTS: Statistically
      significant differences in responses to several survey questions were observed
      comparing pre- and post-course experience. Improvement was noted in comfort
      discussing survivorship issues with patients (p = 0.001), reported knowledge of
      survivorship care for five types of cancer (p = 0.002), confidence in ability to
      explain a SCP (p = 0.001), and comfort discussing late effects of cancer
      treatment (p = 0.001). Five unique sets of TS and SCPs were completed.
      CONCLUSIONS: This study demonstrates the feasibility of implementing cancer
      survivorship education into the curriculum of HO and RO training. IMPLICATIONS
      FOR CANCER SURVIVORS: The project was designed with intension to optimize
      survivor care through enhanced provider training.

PMID- 24307558
TI  - Molecular imaging and pharmacokinetics of (99m) Tc-hTERT antisense
      oligonucleotide as a potential tumor imaging probe.
AB  - Targeting and visualization of human telomerase reverse transcriptase (hTERT)
      represents a promising approach for providing diagnostic value. The uptake
      kinetics and imaging results of (99m) Tc-hTERT antisense oligonucleotides (ASON)
      in hTERT-expressing cells were examined in vitro and in vivo. The
      pharmacokinetics and acute toxicity studies of (99m) Tc-hTERT ASON were also
      performed. The labeling efficiencies of radiolabeled oligonucleotide reached 76
      +/- 5%, the specific activity was up to 1850 kBq/ug, and the radiochemical purity
      was above 96%. Radioactivity accumulated to a higher concentration in hTERT
      expressing cells with antisense probe than with sense control (p < 0.05). Lipid
      carrier incorporation significantly increased the transmembrane delivery of
      radiolabeled probes (p < 0.05). hTERT-expressing xenografts in nude mice were
      clearly visualized at 6 h postinjection of the antisense probe but not the sense
      control probe. However, liposome did not increase the radioactivity accumulation
      of probes in tumors for either antisense or sense probe (p > 0.05). Radioactivity
      counts per minute versus time profiles for (99m) Tc-hTERT ASON were biphasic,
      indicative of a three-compartment model. The pharmacokinetics parameters of half
      life of distribution (T1/2alpha ), half-life of elimination (T1/2beta ), total
      apparent volume of distribution (Vd), and total rate of clearance were 2.04 +/-
      0.48 min, 24 +/- 4.8 min, 109.83 +/- 17.20 mL, and 3.19 +/- 0.17 mL/min,
      respectively. The acute toxicity study results showed the safe application of
      (99m) Tc-hTERT ASON in vivo. This study provides further evidences that (99m) Tc
      hTERT ASON should be developed as a safe, potential molecular image-guided
      diagnostic agent. 

PMID- 24307559
TI  - Test-retest reliability of fMRI activation generated by different saccade tasks.
AB  - PURPOSE: To assess the reproducibility of brain-activation and eye-movement
      patterns in a saccade paradigm when comparing subjects, tasks, and magnetic
      resonance (MR) systems. MATERIALS AND METHODS: Forty-five healthy adults at two
      different sites (n = 45) performed saccade tasks with varying levels of target
      predictability: predictable (PRED), position predictable (pPRED), time
      predictable (tPRED), and prosaccade (SAC). Eye-movement pattern was tested with a
      repeated-measures analysis of variance. Activation maps reproducibility were
      estimated with the cluster overlap Jaccard index and signal variance coefficient
      of determination for within-subjects test-retest data, and for between-subjects
      data from the same and different sites. RESULTS: In all groups latencies
      increased with decreasing target predictability: PRED < pPRED < tPRED < SAC (P <
      0,001). Activation overlap was good to fair (>0.40) in all tasks in the within
      subjects test-retest comparisons and poor (<0.40) in the tPRED for different
      subjects. The overlap of the different tasks for within-groups data was higher
      (0.40-0.68) than for the between-groups data (0.30-0.50). Activation consistency
      was 60-85% in the same subjects, 50-79% in different subjects, and 50-80% in
      different sites. In SAC, the activation found in the same and in different
      subjects was more consistent than in other tasks (50-80%). CONCLUSION: The
      predictive saccade tasks produced evidence for brain-activation and eye-movement
      reproducibility.

PMID- 24307560
TI  - Development of a preliminary pediatric tracheal growth model from magnetic
      resonance images.
AB  - OBJECTIVES/HYPOTHESIS: To develop a growth model of the minimum cross-sectional
      area of the normal pediatric trachea with measurements from magnetic resonance
      images (MRIs) to supplement the clinical criteria used to determine if a child
      with tracheal stenosis needs surgery. STUDY DESIGN: Retrospective imaging review.
      METHODS: A total of 81 patients were imaged for a variety of clinical reasons and
      declared to have normal tracheas fully visible in their T1 magnetic resonance
      image. Regression analysis was used to identify any contribution that age,
      gender, and z scores for height and weight have in predicting the minimum cross
      sectional area of the trachea. RESULTS: The best-fit model for minimum cross
      sectional area is: Area = -0.00451*age(4) + 0.177*age(3) - 2.05*age(2) + 12.6*age
      + 8.02 (area in mm(2) and age in years). Gender and z scores for height and
      weight did not provide any additional explanation of variance in tracheal size.
      CONCLUSIONS: Our study demonstrates the potential to create a growth model of the
      normal trachea based on cross-sectional area of the trachea using MRIs. Even with
      the relatively small number of patients used to build it, the model has
      demonstrated some ability to be used as an objective prediction tool when
      deciding a treatment path for a patient. With continued development of precise,
      objective measures to diagnose the severity of the tracheal stenosis, more
      patients can be given early and accurate prognosis and be treated appropriately.

PMID- 24307561
TI  - Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313
      polymorphisms on resting energy expenditure, leptin and thyrotropin levels in
      obese non-morbid premenopausal women.
AB  - Given that leptin, ghrelin and thyrotropin play a major role in the regulation of
      resting energy expenditure (REE) and that the FTO rs9939609 and the MC4R
      rs17782313 polymorphisms have been proposed to affect energy homeostasis, we
      hypothesized that both polymorphisms are associated with REE and that these
      relationships can be mediated by leptin, ghrelin and thyrotropin in obesity.
      Therefore, the present study aimed to examine the relationships between FTO
      rs9939609 and the MC4R rs17782313 with REE, leptin, ghrelin and thyrotropin
      levels in obese women. The study comprised 77 obese (body mass index 34.0 +/- 2.8
      kg/m(2)) women (age 36.7 +/- 7 years). We measured body composition by dual
      energy X-ray absorptiometry and REE by indirect calorimetry. We analysed fasting
      leptin, ghrelin and thyrotropin levels and the ratio of leptin to fat mass was
      calculated. Genotype distributions of the polymorphisms did not deviate from
      Hardy-Weinberg expectations (P values >0.2). Women carrying the A allele of the
      FTO rs9939609 had lower REE (1,580 +/- 22 vs. 1,739 +/- 35 kcal/day, P < 0.001)
      and higher leptin to fat mass ratio (1.33 +/- 0.05 vs. 1.13 +/- 0.08 ng/ml kg, P
      < 0.05) and thyrotropin levels (1.93 +/- 0.10 vs. 1.53 +/- 0.16 MUU/ml, P < 0.05)
      regardless of age and body mass index. We found no significant influence of the
      MC4R rs17782313 on energy metabolism or biochemical variables. Our findings
      confirm that the A allele of the FTO rs9939609 is associated with lower REE and
      increased plasma leptin levels. We also found an association between the FTO
      rs9939609 and thyrotropin, suggesting the possible influence of FTO in the
      hypothalamic-pituitary-thyroid axis as a potential mechanism of the increased
      adiposity.

PMID- 24307562
TI  - Optimal cut-off value for the number of colorectal liver metastases: a project
      study for hepatic surgery of the Japanese Society of Hepato-Biliary-Pancreatic
      Surgery.
AB  - BACKGROUND: The optimal cut-off value of the number of colorectal liver
      metastases (CRLM) to predict prognosis after hepatic resection remains unclear.
      This study was conducted to determine a suitable cut-off value. METHODS: A total
      of 727 hepatectomized patients with CRLM were evaluated. We proposed the
      following optimal cut-off values: first, a small P-value for the log-rank test
      with no overlapping of the 95% confidence interval (CI) for median survival time
      using the Kaplan-Meier method and the hazard ratio (HR) using the Cox
      proportional hazards model and, second, the maximum HR value for accurate
      separation. RESULTS: For disease-free survival analysis, of the three group
      separations, A2 (1, 2-4, and >=5) showed a small P-value and the largest HR,
      whereas two group separations, B2, B3 and B4 showed similarly small P-values, but
      B4 (1-4, >=5) indicated the largest HR. Regarding the overall survival analysis,
      of the three group separations, A2 showed the smallest P-value, whereas the two
      group separations, B4 showed similarly small P-values, with the largest HR.
      CONCLUSIONS: Tumor number separation in patients with CRLM after hepatic
      resection should be performed using the A2 (1, 2-4, and >=5) or B4 (1-4 and >=5)
      classifications.

PMID- 24307563
TI  - Blood-based testing for colorectal cancer screening.
AB  - Colorectal cancer (CRC) is the third most common non-skin cancer diagnosed in men
      and women in the USA and worldwide. While it has been clearly established that
      screening for CRC, using a variety of methods, is cost effective and has a
      significant impact on overall survival, screening rates have proven to be sub
      optimal. It has been long conjectured that a simple blood-based test, with a
      specimen drawn at a routine doctor's office visit, would encourage those
      individuals who have refused or ignored screening recommendations to undergo
      screening. This article reviews the currently available blood-based screening
      tests for CRC, including the ColonSentryTM messenger RNA (mRNA) expression panel
      and the SEPT9 methylated DNA test, and explores newer biomarkers that are near
      clinical implementation. Also discussed are additional applications for blood
      based CRC testing, such as assessing prognosis, disease surveillance, and
      expansion of screening tests to high-risk populations, such as the estimated 1.4
      million individuals in the USA with inflammatory bowel disease. 

PMID- 24307564
TI  - Versatile and enhanced tumour modelling in mice via somatic cell transduction.
AB  - Genetically engineered mouse (GEM) models of cancer currently comprise the most
      accurate way to experimentally recapitulate the human disease in the laboratory.
      Given recent advances in genomics and genetic screens, however, as well as an
      increasing urgency for the translation of effective preclinical treatments into
      the clinic, there is a pressing need to make these models easier and more
      efficient to work with. Accordingly, we have developed a versatile lentivirus
      based approach to induce tumours from somatic cells of GEMs, add or subtract gene
      expression and render the tumours imageable from a simple breeding stock. The
      vectors deliver a tamoxifen-inducible and self-inactivating Cre recombinase,
      conditional bioluminescent and fluorescent proteins and an shRNA component.
      Following the transduction of somatic cells, tumours are initiated by Cre
      mediated recombination of the inherited floxed alleles. Self-inactivation of Cre
      expression switches on the expression of luciferase, thereby rendering the
      recombined cells and resulting tumours bioluminescent. We demonstrate proof of
      concept of this approach by inducing bioluminescent lung tumours in conditional
      Kras and p53 mice. We also show that a variant vector expressing shRNA alters
      tumour growth dynamics and the histological grade associated with the inherited
      genotype. This approach comprises a versatile means to induce imageable and
      spontaneous tumour burden in mice. The vectors can be readily customized at the
      bench to modify reporter readout or tumour phenotype without additional
      transgenic strain development or breeding. They should also be useful for
      inducing imageable tumours in organs other than the lung, provided that the
      inherited conditional genotype is sufficiently penetrant.

PMID- 24307565
TI  - Stat3 mediates LIF-induced protection of astrocytes against toxic ROS by
      upregulating the UPC2 mRNA pool.
AB  - Reactive oxygen species (ROS) have been implicated in various types of CNS
      damage, including stroke. We used a cultured astrocyte model to explore
      mechanisms of survival of CNS cells following ROS damage. We found that
      pretreatment with leukemia inhibitory factor (LIF) preserves astrocytes exposed
      to toxic levels of t-BHP by inhibiting an increase in intracellular ROS following
      t-BHP treatment. Astrocytes lacking functional Stat3 did not benefit from the pro
      survival or antioxidant effects of LIF. Inhibition of mitochondrial uncoupling
      protein 2 (UCP2) using a chemical inhibitor or siRNA abrogates the prosurvival
      effects of LIF, indicating a critical role for UCP2 in modulation of
      mitochondrial ROS production in survival following ROS exposure. LIF treatment of
      astrocytes results in increased UCP2 mRNA that is accompanied by an increase in
      Stat3 binding to the UCP2 promoter region. Although treatment with LIF alone did
      not increase UCP2 protein, a combination of LIF treatment and ROS stress led to
      increased UCP2 protein levels. We conclude that LIF protects astrocytes from ROS
      induced death by increasing UCP2 mRNA, allowing cells to respond to ROS stress by
      rapidly producing UCP2 protein that ultimately decreases endogenous mitochondrial
      ROS production.

PMID- 24307568
TI  - The 2.05-helix in hetero-oligopeptides entirely composed of C(alpha,alpha)
      disubstituted glycines with both side chains longer than methyls.
AB  - The existence of the very uncommon, but potentially quite interesting, multiple,
      consecutive fully-extended conformation (2.05-helix) has been already clearly
      demonstrated in homo-oligopeptides based on quaternary alpha-amino acids with
      both side chains longer than methyls, but not cyclized on the alpha-carbon atom.
      To extend the scope of this research, in this work we investigated the occurrence
      of this flat 3D-structure in hetero-oligopeptides, each composed of two or three
      different residues of that class. The synthesis of a terminally protected peptide
      series to the tetrapeptide level was carried out by solution methods. The
      resulting oligomers were chemically and conformationally characterized. The data
      obtained point to an overwhelming population of the fully-extended conformation
      in CDCl3. However, a solvent-driven switch to a predominant 310-helical structure
      was seen in CD3CN. A delicate, local balance between these two conformations is
      confirmed to occur in the crystalline state. Molecular dynamics simulations in
      CHCl3 on a hetero-tetrapeptide converged to the fully-extended conformation even
      starting from the 310-helical structure.

PMID- 24307567
TI  - Nested autoinhibitory feedbacks alter the resistance of homeostatic adaptive
      biochemical networks.
AB  - Negative feedback control is a ubiquitous feature of biochemical systems, as is
      time delay between a signal and its response. Negative feedback in conjunction
      with time delay can lead to oscillations. In a cellular context, it might be
      beneficial to mitigate oscillatory behaviour to avoid recurring stress
      situations. This can be achieved by increasing the distance between the
      parameters of the system and certain thresholds, beyond which oscillations occur.
      This distance has been termed resistance. Here, we prove that in a generic three
      dimensional negative feedback system the resistance of the system is modified by
      nested autoinhibitory feedbacks. Our system features negative feedbacks through
      both input-inhibition as well as output-activation, a signalling component with
      mass conservation and perfect adaptation. We show that these features render the
      system applicable to biological data, exemplified by the high osmolarity glycerol
      system in yeast and the mammalian p53 system. Output-activation is better
      supported by data than input-inhibition and also shows distinguished properties
      with respect to the system's stimulus. Our general approach might be useful in
      designing synthetic systems in which oscillations can be tuned by synthetic
      autoinhibitory feedbacks. 

PMID- 24307569
TI  - Maternal genetic polymorphisms of phase II metabolic enzymes and the risk of
      fetal neural tube defects.
AB  - BACKGROUND: Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been
      associated with the risk of fetal neural tube defects (NTDs). Whether maternal
      genetic variants related to PAH metabolism contribute to the development of fetal
      NTDs remains unclear. METHODS: We conducted a case-control study in a Chinese
      population to examine the association of selected maternal genetic variants of
      phase II enzymes involved in the elimination of the metabolic intermediates of
      these chemicals with fetal NTD risk, and to evaluate possible interaction of the
      genetic variant and maternal exposure to indoor air pollution from coal
      combustion and smoking (IAPCC). Blood samples were collected from 534 NTD case
      mothers and 534 control mothers and assayed for 12 polymorphisms of 5 genes
      encoding phase II enzymes. RESULTS: We found that the rs9282861 GG genotype of
      SULT1A1 was associated with an elevated risk of total NTDs (odds ratio [OR] =
      2.12, 95% confidence interval [CI]: 1.49-3.00), compared with the GA genotype.
      The SULT1A1 rs9282861 variant showed a significant additive interaction with
      maternal exposure to IAPCC for NTD risk, with a relative excess risk of
      interaction of 1.20 (95% CI 0.23-2.18), and the OR for the joint effect of high
      level IAPCC exposure and the GG genotype was 8.37 (95% CI: 3.63-19.28).
      CONCLUSION: Maternal SULT1A1 polymorphism is associated with the risk of fetal
      NTDs, and has an additive-scale interaction with maternal IAPCC exposure for NTD
      risk.

PMID- 24307566
TI  - Reverse engineering and identification in systems biology: strategies,
      perspectives and challenges.
AB  - The interplay of mathematical modelling with experiments is one of the central
      elements in systems biology. The aim of reverse engineering is to infer, analyse
      and understand, through this interplay, the functional and regulatory mechanisms
      of biological systems. Reverse engineering is not exclusive of systems biology
      and has been studied in different areas, such as inverse problem theory, machine
      learning, nonlinear physics, (bio)chemical kinetics, control theory and
      optimization, among others. However, it seems that many of these areas have been
      relatively closed to outsiders. In this contribution, we aim to compare and
      highlight the different perspectives and contributions from these fields, with
      emphasis on two key questions: (i) why are reverse engineering problems so hard
      to solve, and (ii) what methods are available for the particular problems arising
      from systems biology? 

PMID- 24307570
TI  - Simple method for whole-brain volumetric T(1)-weighted turbo spin-echo imaging.
AB  - We propose a simple scheme of 3D turbo spin echo (TSE) with low-refocusing flip
      angles (RFAs) for obtaining sufficient T1-weighted contrast. The low RFA can
      easily lead spins into a pseudo-steady-state (PSS) condition, but a preparation
      scheme is required for smooth transition into static PSS. For obtaining T1
      contrast, PSS preparation is the most important factor, and therefore we focused
      on the PSS preparation. To optimize the T1 contrast in the proposed sequence, we
      compared the following parameters: RFAs of 90 degrees  and 30 degrees , and a PSS
      preparation scheme of "90 degrees  + alpha/2" and asymptotic preparation.
      Subsequently, to demonstrate the quality of the proposed sequence, we compared
      the image quality regarding conventional 3D TSE and 2D spin echo (SE). A
      combination of an RFA of 30 degrees  and the "90 degrees  + alpha/2" preparation
      scheme showed the highest T1 contrast. The optimized sequence provided higher
      contrast and sharper images compared to 3D TSE, and it showed contrast and a
      signal-to-noise ratio similar to those of 2D SE. 

PMID- 24307571
TI  - Dynamic contrast-enhanced MRI to evaluate the therapeutic response to neoadjuvant
      chemoradiation therapy in locally advanced rectal cancer.
AB  - PURPOSE: To evaluate the usefulness of perfusion parameters derived from dynamic
      contrast-enhanced MR imaging (DCE-MRI) for assessing the therapeutic response to
      neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer
      (LARC). MATERIALS AND METHODS: Fifty patients with LARC (>=T3 or lymph-node
      metastasis) who underwent CRT and subsequent surgery, were included in this
      study. All patients underwent pre- and post-CRT DCE-MRI on a 1.5 Tesla unit. By
      using a postprocessing software, the following perfusion parameters (K(trans) ,
      kep , ve ) were measured for tumor. Those perfusion parameters were compared not
      only between the T-downstaged group and the nondownstaged group, but also before
      and after CRT in each group. RESULTS: After CRT, the mean K(trans) (min(-1) )
      significantly decreased from 1.24 +/- 0.53 to 0.76 +/- 0.45 in the T-downstaged
      group (n = 24) (P = 0.0007), whereas it did not significantly decrease in the
      nondownstaged group (n = 26) (from 1.02 +/- 0.53 to 0.87 +/- 0.48, P = 0.24). The
      percentage difference between pre- and post-CRT K(trans) in the T-downstaged
      group was significantly higher than that in the nondownstaged group (43%, 16%,
      respectively, P = 0.0092). However, none of the other parameters showed
      significant differences. CONCLUSION: A large decrease in the mean K(trans) after
      CRT was associated with a good therapeutic response to CRT for LARC.

PMID- 24307572
TI  - Three-dimensional whole-brain perfusion quantification using pseudo-continuous
      arterial spin labeling MRI at multiple post-labeling delays: accounting for both
      arterial transit time and impulse response function.
AB  - Measurement of the cerebral blood flow (CBF) with whole-brain coverage is
      challenging in terms of both acquisition and quantitative analysis. In order to
      fit arterial spin labeling-based perfusion kinetic curves, an empirical three
      parameter model which characterizes the effective impulse response function (IRF)
      is introduced, which allows the determination of CBF, the arterial transit time
      (ATT) and T(1,eff). The accuracy and precision of the proposed model were
      compared with those of more complicated models with four or five parameters
      through Monte Carlo simulations. Pseudo-continuous arterial spin labeling images
      were acquired on a clinical 3-T scanner in 10 normal volunteers using a three
      dimensional multi-shot gradient and spin echo scheme at multiple post-labeling
      delays to sample the kinetic curves. Voxel-wise fitting was performed using the
      three-parameter model and other models that contain two, four or five unknown
      parameters. For the two-parameter model, T(1,eff) values close to tissue and
      blood were assumed separately. Standard statistical analysis was conducted to
      compare these fitting models in various brain regions. The fitted results
      indicated that: (i) the estimated CBF values using the two-parameter model show
      appreciable dependence on the assumed T(1,eff) values; (ii) the proposed three
      parameter model achieves the optimal balance between the goodness of fit and
      model complexity when compared among the models with explicit IRF fitting; (iii)
      both the two-parameter model using fixed blood T1 values for T(1,eff) and the
      three-parameter model provide reasonable fitting results. Using the proposed
      three-parameter model, the estimated CBF (46 +/- 14 mL/100 g/min) and ATT (1.4 +/
      0.3 s) values averaged from different brain regions are close to the literature
      reports; the estimated T(1,eff) values (1.9 +/- 0.4 s) are higher than the tissue
      T1 values, possibly reflecting a contribution from the microvascular arterial
      blood compartment.

PMID- 24307573
TI  - Benzoboroxole-functionalized magnetic core/shell microspheres for highly specific
      enrichment of glycoproteins under physiological conditions.
AB  - Efficient enrichment of specific glycoproteins from complex biological samples is
      of great importance towards the discovery of disease biomarkers in biological
      systems. Recently, phenylboronic acid-based functional materials have been widely
      used for enrichment of glycoproteins. However, such enrichment was mainly carried
      out under alkaline conditions, which is different to the status of glycoproteins
      in neutral physiological conditions and may cause some unpredictable degradation.
      In this study, on-demand neutral enrichment of glycoproteins from crude
      biological samples is accomplished by utilizing the reversible interaction
      between the cis-diols of glycoproteins and benzoboroxole-functionalized magnetic
      composite microspheres (Fe3O4/PAA-AOPB). The Fe3O4/PAA-AOPB composite
      microspheres are deliberately designed and constructed with a high-magnetic
      response magnetic supraparticle (MSP) core and a crosslinked poly(acrylic acid)
      (PAA) shell anchoring abundant benzoboroxole functional groups on the surface.
      These nanocomposites possessed many merits, such as large enrichment capacity
      (93.9 mg/g, protein/beads), low non-specific adsorption, quick enrichment process
      (10 min) and magnetic separation speed (20 s), and high recovery efficiency.
      Furthermore, the as-prepared Fe3O4/PAA-AOPB microspheres display high selectivity
      to glycoproteins even in the E. coli lysate or fetal bovine serum, showing great
      potential in the identify of low-abundance glycoproteins as biomarkers in real
      complex biological systems for clinical diagnoses.

PMID- 24307575
TI  - Abstracts of the 138th Meeting of the American Neurological Association. October
      13-16, 2013. New Orleans, Louisiana, USA.

PMID- 24307576
TI  - Comparison of the AJCC N staging system in mucosal and cutaneous squamous head
      and neck cancer.
AB  - OBJECTIVES/HYPOTHESIS: The American Joint Committee on Cancer (AJCC)
      substantially changed the staging of cutaneous squamous cell carcinoma (cSCC) in
      the seventh edition of its staging manual. Given that oral mucosal squamous cell
      carcinoma (mSCC) and cSCC behave differently and affect different patient
      populations, the aim of this study was to provide a side-by-side comparison and
      to evaluate the current nodal (N) grouping for cSCC alongside oral mSCC to
      determine whether the same system is justified. STUDY DESIGN: Retrospective
      analysis of prospectively collected data. METHODS: Multivariable analysis of 672
      patients with metastatic cSCC and of 225 patients with metastatic mSCC from two
      prospective cancer-center databases. RESULTS: While, as expected, the N grouping
      functioned well in mSCC in terms of distribution and stratification of patients,
      it performed much less favorably in cSCC. In contrast to mSCC, the different N
      groups demonstrate much less prognostic importance in cSCC. CONCLUSION: Although
      the introduction of a unified N system for mSCC and cSCC has definite advantages,
      it does not translate into optimal distribution and stratification for metastatic
      cSCC. LEVEL OF EVIDENCE: 4.

PMID- 24307574
TI  - Expression of chimeric receptor CD4zeta by natural killer cells derived from
      human pluripotent stem cells improves in vitro activity but does not enhance
      suppression of HIV infection in vivo.
AB  - Cell-based immunotherapy has been gaining interest as an improved means to treat
      human immunodeficiency virus (HIV)/AIDS. Human embryonic stem cells (hESCs) and
      induced pluripotent stem cells (iPSCs) could become a potential resource. Our
      previous studies have shown hESC and iPSC-derived natural killer (NK) cells can
      inhibit HIV-infected targets in vitro. Here, we advance those studies by
      expressing a HIV chimeric receptor combining the extracellular portion of CD4 to
      the CD3zeta intracellular signaling chain. We hypothesized that expression of
      this CD4zeta receptor would more efficiently direct hESC- and iPSC-derived NK
      cells to target HIV-infected cells. In vitro studies showed the CD4zeta
      expressing hESC- and iPSC-NK cells inhibited HIV replication in CD4+ T-cells more
      efficiently than their unmodified counterparts. We then evaluated CD4zeta
      expressing hESC (CD4zeta-hESC)- and iPSC-NK cells in vivo anti-HIV activity using
      a humanized mouse model. We demonstrated significant suppression of HIV
      replication in mice treated with both CD4zeta-modified and -unmodified hESC-/iPSC
      NK cells compared with control mice. However, we did not observe significantly
      increased efficacy of CD4zeta expression in suppression of HIV infection. These
      studies indicate that hESC/iPSC-based immunotherapy can be used as a unique
      resource to target HIV/AIDS.

PMID- 24307577
TI  - Interleukin-10 promoter (-1082) polymorphism in association with repeated
      hospital-acquired infections in elderly patients.
AB  - BACKGROUND: Infections are frequent complications of hospitalization,
      particularly in the elderly. Pro- and anti-inflammatory cytokines are essential
      components of the host response to pathogens and polymorphisms in their genes may
      contribute to inter-individual variations of the inflammatory response. The aim
      of this study was to investigate whether cytokine polymorphisms, separately or in
      combination, could be determining factors in the development of repeated
      nosocomial infections in elderly hospitalized patients. METHODS: Tumor necrosis
      factor-alpha (-308) and (-238), interleukin-6 (-174) and (-6331), interleukin-10
      (-1082) and (-592) polymorphisms were genotyped by PCR and hybridization with
      fluorescent-labeled probes in 245 hospitalized elderly patients (mean age 85.2
      years; SD 6) and compared with those in 145 healthy adults. RESULTS: The
      distribution of genotypes did not differ between elderly patients and control
      subjects. The presence of the interleukin-10 A(592) or A(1082) allele was more
      frequent individually and after adjustment for multiple comparisons in patients
      who suffered from several infections (p = 0.012, odds ratio = 5.3; 95 %
      confidence interval = 1.2-23.1). CONCLUSION: Our data support a determinant role
      for interleukin-10 (-1082) polymorphism in the development of nosocomial
      infections.

PMID- 24307578
TI  - Simple verbal analogies test: normative data on a short task exploring abstract
      thinking.
AB  - BACKGROUND AND AIMS: The simple verbal analogies test (SVAT) is a short
      neuropsychological task requiring few minutes of administration that explores
      inductive verbal abstract thinking. It already showed a good specificity and
      sensitivity in discriminating normal controls from probable Alzheimer's disease
      patients. Verbal working memory, semantic knowledge and memory and word-finding
      ability are also involved in performing analogies. The aim of this study is to
      provide the normative values of this test in a sample of normal controls and
      corrections of raw scores and equivalent scores. METHODS AND RESULTS: We
      determined the normative values of SVAT in a sample of 424 normal controls to
      provide corrections of raw scores and equivalent scores. CONCLUSIONS: SVAT is a
      useful test to assess executive functions, working memory and to discriminate
      between cognitive deterioration and normal aging.

PMID- 24307579
TI  - Inhibition of hepatitis C virus production by aptamers against the core protein.
AB  - Hepatitis C virus (HCV) core protein is essential for virus assembly. HCV core
      protein was expressed and purified. Aptamers against core protein were raised
      through the selective evolution of ligands by the exponential enrichment
      approach. Detection of HCV infection by core aptamers and the antiviral
      activities of aptamers were characterized. The mechanism of their anti-HCV
      activity was determined. The data showed that selected aptamers against core
      specifically recognize the recombinant core protein but also can detect serum
      samples from hepatitis C patients. Aptamers have no effect on HCV RNA replication
      in the infectious cell culture system. However, the aptamers inhibit the
      production of infectious virus particles. Beta interferon (IFN-beta) and
      interferon-stimulated genes (ISGs) are not induced in virally infected
      hepatocytes by aptamers. Domains I and II of core protein are involved in the
      inhibition of infectious virus production by the aptamers. V31A within core is
      the major resistance mutation identified. Further study shows that the aptamers
      disrupt the localization of core with lipid droplets and NS5A and perturb the
      association of core protein with viral RNA. The data suggest that aptamers
      against HCV core protein inhibit infectious virus production by disrupting the
      localization of core with lipid droplets and NS5A and preventing the association
      of core protein with viral RNA. The aptamers for core protein may be used to
      understand the mechanisms of virus assembly. Core-specific aptamers may hold
      promise for development as early diagnostic reagents and potential therapeutic
      agents for chronic hepatitis C. 

PMID- 24307580
TI  - Quantification of entry phenotypes of macrophage-tropic HIV-1 across a wide range
      of CD4 densities.
AB  - Defining a macrophage-tropic phenotype for HIV-1 to assess a role in pathogenesis
      is complicated by the fact that HIV-1 isolates vary continuously in their ability
      to enter monocyte-derived macrophages (MDMs) in vitro, and MDMs vary in their
      ability to support HIV-1 entry. To overcome these limitations, we identified
      consistent differences in entry phenotypes between five paired blood-derived, T
      cell-tropic HIV-1 env genes, four of which are CCR5-using (R5) and one of which
      is CXCR4-using (X4), and cerebrospinal fluid (CSF)-derived, R5 macrophage-tropic
      env genes. We performed entry assays using the CD4- and CCR5-inducible Affinofile
      cell line, expressing a range of CD4 levels that approximates the range from MDMs
      to CD4(+) T cells. The macrophage-tropic viruses were significantly better at
      infecting cells expressing low levels of CD4 than the T cell-tropic viruses from
      the same subjects, with the titration of CD4 providing a distinctive and
      quantitative phenotype. This difference in CD4 utilization was not due to
      macrophage-tropic viruses being CD4 independent. Furthermore, macrophage-tropic
      viruses did not differ from paired T cell-tropic viruses in their ability to use
      low levels of CCR5 (tpaired = -1.39; P = 0.24) or their use of an alternative
      conformation of CCR5. We also infected MDMs with a panel of viruses and observed
      that infectivity of each virus differed across four donors and between three
      preparations from a single donor. We concluded that the evolutionary transition
      from replication in T cells to that in macrophages involves a phenotypic
      transition to acquire the ability to infect cells expressing low levels of CD4
      and that this phenotype is more reliably measured in Affinofile cells than in
      macrophages. IMPORTANCE HIV-1 typically infects memory T cells by using CD4 and
      CCR5 to enter cells. The virus evolves to infect new cell types by changing the
      coreceptor from CCR5 to CXCR4 to infect naive T cells or adapting to the use of
      low levels of CD4 to infect macrophages. However, defining the phenotype of
      macrophage tropism has been difficult due to inherent variability in the use of
      macrophages generated in culture to support entry of HIV-1. We describe the use
      of Affinofile cells with inducible and variable levels of CD4 to identify a
      signature phenotype for macrophage-tropic HIV-1. The ability to define HIV-1
      variants that have evolved an entry phenotype that allows more efficient entry
      into cells with low levels of CD4 sets the stage for a clearer placement of these
      variants in HIV-associated pathogenesis. 

PMID- 24307581
TI  - A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge
      with simian immunodeficiency virus SIVmac251.
AB  - As an alternative to targeting human immunodeficiency virus (HIV), we have
      developed vaccines targeting CCR5, a self-protein critically involved in HIV
      replication and pathogenesis. By displaying peptides derived from CCR5 at high
      density on the surface of virus-like particles, we can efficiently induce high
      titer IgG antibodies against this self-molecule. Here, we investigated whether
      prophylactic immunization of rhesus macaques with a particle-based vaccine
      targeting two regions of macaque CCR5 could prevent or suppress vaginal infection
      with highly virulent SIVmac251. Twelve macaques were vaccinated with a
      bacteriophage Qbeta-based vaccine targeting macaque CCR5 (Qbeta.CCR5). Six
      control animals were immunized with the Qbeta platform alone. All animals
      immunized with Qbeta.CCR5 developed high-titer anti-CCR5 antibody responses.
      Macaques were vaginally challenged with a high dose of SIVmac251. The mean peak
      viral RNA levels in the vaccinated groups were 30-fold lower than in the control
      group (10(6.8) versus 10(8.3) copies/ml plasma). Three of the 12 vaccinated
      macaques dramatically suppressed simian immunodeficiency virus (SIV) replication:
      peak viral loads were low (10(3) to 10(4) RNA copies/ml), and SIV RNA became
      undetectable from 6 weeks onward. No viral RNA or DNA could be detected in colon
      and lymph node biopsy specimens collected 13 months after challenge. In vivo
      depletion of CD8(+) cells failed to induce a viral rebound. However, once anti
      CCR5 antibody responses had waned, the 3 animals became infected after
      intravaginal and/or intravenous rechallenge. In conclusion, vaccination against
      CCR5 was associated with dramatic suppression of virus replication in a subset
      (25%) of macaques. These data support further research of vaccination against
      CCR5 to combat HIV infection. 

PMID- 24307582
TI  - Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated
      transcript during herpes simplex virus 1 latency.
AB  - Herpesvirus entry mediator (HVEM) is one of several cell surface proteins herpes
      simplex virus (HSV) uses for attachment/entry. HVEM regulates cellular immune
      responses and can also increase cell survival. Interestingly, latency-associated
      transcript (LAT), the only viral gene consistently expressed during neuronal
      latency, enhances latency and reactivation by promoting cell survival and by
      helping the virus evade the host immune response. However, the mechanisms of
      these LAT activities are not well understood. We show here for the first time
      that one mechanism by which LAT enhances latency and reactivation appears to be
      by upregulating HVEM expression. HSV-1 latency/reactivation was significantly
      reduced in Hvem(-/-) mice, indicating that HVEM plays a significant role in HSV-1
      latency/reactivation. Furthermore, LAT upregulated HVEM expression during latency
      in vivo and also when expressed in vitro in the absence of other viral factors.
      This study suggests a mechanism whereby LAT upregulates HVEM expression
      potentially through binding of two LAT small noncoding RNAs to the HVEM promoter
      and that the increased HVEM then leads to downregulation of immune responses in
      the latent microenvironment and increased survival of latently infected cells.
      Thus, one of the mechanisms by which LAT enhances latency/reactivation appears to
      be through increasing expression of HVEM. 

PMID- 24307583
TI  - Two novel proteins of cyanophage Syn5 compose its unusual horn structure.
AB  - The marine cyanophage Syn5 can be propagated to a high titer in the laboratory on
      marine photosynthetic Synechococcus sp. strain WH8109. The purified particles
      carry a novel slender horn structure projecting from the vertex opposite the tail
      vertex. The genome of Syn5 includes a number of genes coding for novel proteins.
      Using immune-electron microscopy with gold-labeled antibodies, we show that two
      of these novel proteins, products of genes 53 and 54, are part of the horn
      structure. A third novel protein, the product of gene 58, is assembled onto the
      icosahedral capsid lattice. Characterization of radioactively labeled precursor
      procapsids by sucrose gradient centrifugation shows that there appear to be three
      classes of particles-procapsids, scaffold-deficient procapsids, and expanded
      capsids. These lack fully assembled horn appendages. The horn presumably
      assembles onto the virion just before or after DNA packaging. Antibodies raised
      to the recombinant novel Syn5 proteins did not interfere with phage infectivity,
      suggesting that the functions of these proteins are not directly involved in
      phage attachment or infection of the host WH8109. The horn structure may
      represent some adaption to the marine environment, whose function will require
      additional investigation. 

PMID- 24307584
TI  - A versatile RNA vector for delivery of coding and noncoding RNAs.
AB  - The discovery that RNA viruses, lacking any DNA intermediate, can be engineered
      to express both coding and noncoding RNAs suggests that this platform may have
      therapeutic value as a delivery vehicle. Here we illustrate that a self
      replicating, noninfectious RNA, modeled on influenza virus, provides one such
      example of a versatile in vivo delivery system for silencing and/or expressing a
      desired RNA for therapeutic purposes. 

PMID- 24307585
TI  - H3 stalk-based chimeric hemagglutinin influenza virus constructs protect mice
      from H7N9 challenge.
AB  - The recent outbreak of H7N9 influenza virus infections in humans in China has
      raised concerns about the pandemic potential of this strain. Here, we test the
      efficacy of H3 stalk-based chimeric hemagglutinin universal influenza virus
      vaccine constructs to protect against H7N9 challenge in mice. Chimeric
      hemagglutinin constructs protected from viral challenge in the context of
      different administration routes as well as with a generic oil-in-water adjuvant
      similar to formulations licensed for use in humans. 

PMID- 24307587
TI  - Expression of herpes simplex virus 1 microRNAs in cell culture models of
      quiescent and latent infection.
AB  - To facilitate studies of herpes simplex virus 1 latency, cell culture models of
      quiescent or latent infection have been developed. Using deep sequencing, we
      analyzed the expression of viral microRNAs (miRNAs) in two models employing human
      fibroblasts and one using rat neurons. In all cases, the expression patterns
      differed from that in productively infected cells, with the rat neuron pattern
      most closely resembling that found in latently infected human or mouse ganglia in
      vivo. 

PMID- 24307586
TI  - De novo prion aggregates trigger autophagy in skeletal muscle.
AB  - In certain sporadic, familial, and infectious prion diseases, the prion protein
      misfolds and aggregates in skeletal muscle in addition to the brain and spinal
      cord. In myocytes, prion aggregates accumulate intracellularly, yet little is
      known about clearance pathways. Here we investigated the clearance of prion
      aggregates in muscle of transgenic mice that develop prion disease de novo. In
      addition to neurodegeneration, aged mice developed a degenerative myopathy, with
      scattered myocytes containing ubiquitinated, intracellular prion inclusions that
      were adjacent to myocytes lacking inclusions. Myocytes also showed elevated
      levels of the endoplasmic reticulum chaperone Grp78/BiP, suggestive of impaired
      protein degradation and endoplasmic reticulum stress. Additionally, autophagy was
      induced, as indicated by increased levels of beclin-1 and LC3-II. In C2C12
      myoblasts, inhibition of autophagosome maturation or lysosomal degradation led to
      enhanced prion aggregation, consistent with a role for autophagy in prion
      aggregate clearance. Taken together, these findings suggest that the induction of
      autophagy may be a central strategy for prion aggregate clearance in myocytes.
      IMPORTANCE In prion diseases, the prion protein misfolds and aggregates in the
      central nervous system and sometimes in other organs, including muscle, yet the
      cellular pathways of prion aggregate clearance are unclear. Here we investigated
      the clearance of prion aggregates in the muscle of a transgenic mouse model that
      develops profound muscle degeneration. We found that endoplasmic reticulum stress
      pathways were activated and that autophagy was induced. Blocking of autophagic
      degradation in cell culture models led to an accumulation of aggregated prion
      protein. Collectively, these findings suggest that autophagy has an instrumental
      role in prion protein clearance. 

PMID- 24307588
TI  - High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by
      the macrophage-T cell virological synapse.
AB  - Macrophage infection is considered to play an important role in HIV-1
      pathogenesis and persistence. Using a primary cell-based coculture model, we show
      that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity
      HIV-1 infection to autologous CD4(+) T cells through a viral envelope
      glycoprotein (Env) receptor- and actin-dependent virological synapse (VS),
      facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)
      mediated transmission by MDM results in high levels of T cell HIV-1 integration
      and is 1 to 2 orders of magnitude more efficient than cell-free infection. This
      mode of cell-to-cell transmission is broadly susceptible to the activity of CD4
      binding site (CD4bs) and glycan or glycopeptide epitope-specific broadly
      neutralizing monoclonal antibodies (bNMAbs) but shows resistance to bNMAbs
      targeting the Env gp41 subunit membrane-proximal external region (MPER). These
      data define for the first time the structure and function of the macrophage-to-T
      cell VS and have important implications for bNMAb activity in HIV-1 prophylaxis
      and therapy. IMPORTANCE The ability of HIV-1 to move directly between contacting
      immune cells allows efficient viral dissemination with the potential to evade
      antibody attack. Here, we show that HIV-1 spreads from infected macrophages to T
      cells via a structure called a virological synapse that maintains extended
      contact between the two cell types, allowing transfer of multiple infectious
      events to the T cell. This process allows the virus to avoid neutralization by a
      class of antibody targeting the gp41 subunit of the envelope glycoproteins. These
      results have implications for viral spread in vivo and the specificities of
      neutralizing antibody elicited by antibody-based vaccines. 

PMID- 24307589
TI  - Internal ribosome entry site-based attenuation of a flavivirus candidate vaccine
      and evaluation of the effect of beta interferon coexpression on vaccine
      properties.
AB  - Infectious clone technologies allow the rational design of live attenuated viral
      vaccines with the possibility of vaccine-driven coexpression of immunomodulatory
      molecules for additional vaccine safety and efficacy. The latter could lead to
      novel strategies for vaccine protection against infectious diseases where
      traditional approaches have failed. Here we show for the flavivirus Murray Valley
      encephalitis virus (MVEV) that incorporation of the internal ribosome entry site
      (IRES) of Encephalomyocarditis virus between the capsid and prM genes strongly
      attenuated virulence and that the resulting bicistronic virus was both
      genetically stable and potently immunogenic. Furthermore, the novel bicistronic
      genome organization facilitated the generation of a recombinant virus carrying an
      beta interferon (IFN-beta) gene. Given the importance of IFNs in limiting virus
      dissemination and in efficient induction of memory B and T cell antiviral
      immunity, we hypothesized that coexpression of the cytokine with the live vaccine
      might further increase virulence attenuation without loss of immunogenicity. We
      found that bicistronic mouse IFN-beta coexpressing MVEV yielded high virus and
      IFN titers in cultured cells that do not respond to the coexpressed IFN. However,
      in IFN response-sufficient cell cultures and mice, the virus produced a self
      limiting infection. Nevertheless, the attenuated virus triggered robust innate
      and adaptive immune responses evidenced by the induced expression of Mx proteins
      (used as a sensitive biomarker for measuring the type I IFN response) and the
      generation of neutralizing antibodies, respectively. IMPORTANCE The family
      Flaviviridae includes a number of important human pathogens, such as Dengue
      virus, Yellow fever virus, Japanese encephalitis virus, West Nile virus, and
      Hepatitis C virus. Flaviviruses infect large numbers of individuals on all
      continents. For example, as many as 100 million people are infected annually with
      Dengue virus, and 150 million people suffer a chronic infection with Hepatitis C
      virus. However, protective vaccines against dengue and hepatitis C are still
      missing, and improved vaccines against other flaviviral diseases are needed. The
      present study investigated the effects of a redesigned flaviviral genome and the
      coexpression of an antiviral protein (interferon) on virus replication,
      pathogenicity, and immunogenicity. Our findings may aid in the rational design of
      a new class of well-tolerated and safe vaccines. 

PMID- 24307590
TI  - Stable, high-level expression of reporter proteins from improved alphavirus
      expression vectors to track replication and dissemination during encephalitic and
      arthritogenic disease.
AB  - Engineered alphavirus vectors expressing reporters of infection have been used
      for a number of years due to their relatively low costs for analysis of virus
      replication and the capacity to utilize imaging systems for longitudinal
      measurements of growth within single animals. In general, these vectors have been
      derived from Old World alphaviruses using a second viral subgenomic promoter to
      express the transgenes, placed either immediately after the nonstructural
      proteins or at the 3' end of the viral coding sequences. However, the relevance
      of these vectors to natural infections is questionable, as they have not been
      rigorously tested for virulence in vivo in comparison with parental viruses or
      for the retention of the reporter during replication. Here, we report
      construction of new expression vectors for two Old World arthritogenic
      alphaviruses (Sindbis and Chikungunya viruses) and two New World encephalitic
      alphaviruses (eastern and Venezuelan equine encephalitis viruses) based upon
      either fusion of the reporter protein in frame within nonstructural protein 3
      (nsP3) or insertion of the reporter as a cleavable element between the capsid and
      PE2 structural proteins. We have compared these with a traditional 3' double
      subgenomic promoter virus expressing either a large, firefly luciferase (fLuc;
      1,650 nucleotides), or small, NanoLuc (nLuc; 513 nucleotides), luminescent
      reporter protein. Results indicate that the nLuc is substantially more stable
      than fLuc during repeated rounds of infection regardless of the transgene
      location. However, the capsid-PE2 insertion and nsP3 fusion viruses exhibit the
      most authentic mimicking of parental virus infection regardless of expressed
      protein. IMPORTANCE As more antiviral therapeutics and vaccines are developed,
      rapid and accurate in vivo modeling of their efficacy will be required. However,
      current alphavirus vectors expressing reporters of infection have not been
      extensively tested for accurate mimicking of the infection characteristics of
      unmodified parental viruses. Additionally, use of in vivo imaging systems
      detecting light emitted from luciferase reporters can significantly decrease
      costs associated with efficacy studies by minimizing numbers of animals. Herein
      we report development and testing of new expression vectors for Sindbis,
      Chikungunya, and eastern and Venezuelan equine encephalitis viruses and
      demonstrate that a small (~500-nucleotide) reporter gene (NanoLuc; Promega) is
      very stable and causes a disease severity similar to that caused by unmodified
      parental viruses. In contrast, expression of larger reporters is very rapidly
      lost with virus replication and can be significantly attenuating. The utility of
      NanoLuc for in vivo imaging is also demonstrated. 

PMID- 24307591
TI  - Proximity of the maxillary artery to the mandibular ramus: an anatomic study
      using three-dimensional reconstruction of computer tomography.
AB  - The maxillary artery (MA) is the main source of brisk bleeding during
      maxillectomy and procedures in the subcondylar portion of the mandible. The
      purpose of the study was to investigate the relationship between the MA and the
      mandible in the infratemporal fossa. The CT scans of 100 patients were
      retrospectively evaluated. The distances from the MA to bony landmarks were
      assessed in a three-dimensional model of the CT scan. In the cases where the MA
      was lateral to the LP [164 of 200 MAs (82%)], the mean shortest distances from
      the MA to the apex of the coronoid and condyle and the deepest portion of the
      mandibular notch were 13.6 +/- 1.6 mm, 21.3 +/- 2.0 mm, and 3.6 +/- 1.0 mm,
      respectively. The contact point between the MA and medial surface of the mandible
      was measured and found to be 3.6 +/- 2.2 mm posterior and 1.7 +/- 1.4 mm inferior
      relative to the deepest portion of the mandibular notch. In the cases where the
      MA was medial to the LP [36 of 200 MAs (18%)], the mean shortest distances from
      the MA to the apex of the coronoid and condyle and the deepest portion of the
      mandibular notch were 19.5 +/- 2.5 mm, 20.7 +/- 2.4 mm, and 16.3 +/- 3.7 mm,
      respectively. The studied measurements will help guide surgeons to determine the
      anatomy of the operative field in relation to the MA and minimize risks of
      injuring the vessel.

PMID- 24307592
TI  - The small heat-shock protein alphaB-crystallin is essential for the nuclear
      localization of Smad4: impact on pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the
      proliferation of myofibroblasts and the accumulation of extracellular matrix
      (ECM) in the lungs. TGF-beta1 is the major profibrotic cytokine involved in IPF
      and is responsible for myofibroblast proliferation and differentiation and ECM
      synthesis. alphaB-crystallin is constitutively expressed in the lungs and is
      inducible by stress, acts as a chaperone and is known to play a role in cell
      cytoskeleton architecture homeostasis. The role of alphaB-crystallin in
      fibrogenesis remains unknown. The principal signalling pathway involved in this
      process is the Smad-dependent pathway. We demonstrate here that alphaB-crystallin
      is strongly expressed in fibrotic lung tissue from IPF patients and in vivo
      rodent models of pulmonary fibrosis. We also show that alphaB-crystallin
      deficient mice are protected from bleomycin-induced fibrosis. Similar protection
      from fibrosis was observed in alphaB-crystallin KO mice after transient
      adenoviral-mediated over-expression of IL-1beta or TGF-beta1. We show in vitro in
      primary epithelial cells and fibroblasts that alphaB-crystallin increases the
      nuclear localization of Smad4, thereby enhancing the TGF-beta1-Smad pathway and
      the consequent activation of TGF-beta1 downstream genes. alphaB-crystallin over
      expression disrupts Smad4 mono-ubiquitination by interacting with its E3
      ubiquitin ligase, TIF1gamma, thus limiting its nuclear export. Conversely, in the
      absence of alphaB-crystallin, TIF1gamma can freely interact with Smad4.
      Consequently, Smad4 mono-ubiquitination and nuclear export are favoured and thus
      TGF-beta1-Smad4 pro-fibrotic activity is inhibited. This study demonstrates that
      alphaB-crystallin may be a key target for the development of specific drugs in
      the treatment of IPF or other fibrotic diseases.

PMID- 24307593
TI  - Resonances in the entrance channel of the elementary chemical reaction of
      fluorine and methane.
AB  - Extending the fully quantum-state-resolved description of elementary chemical
      reactions beyond three or four atom systems is a crucial issue in fundamental
      chemical research. Reactions of methane with F, Cl, H or O are key examples that
      have been studied prominently. In particular, reactive resonances and
      nonintuitive mode-selective chemistry have been reported in experimental studies
      for the F+CH4 ->HF+CH3 reaction. By investigating this reaction using transition
      state spectroscopy, this joint theoretical and experimental study provides a
      clear picture of resonances in the F+CH4 system. This picture is deduced from
      high-resolution slow electron velocity-map imaging (SEVI) spectra and accurate
      full-dimensional (12D) quantum dynamics simulations in the picosecond regime. 

PMID- 24307594
TI  - Patient with disorganization syndrome: surgical procedures, pathology, and
      potential causes.
AB  - BACKGROUND: The human disorganization syndrome (HDS) is an extremely rare
      malformation syndrome that presents with a severe pattern of defects affecting
      different structures. METHODS: We describe a newborn girl presenting with HDS.
      Her clinical features included a large appendage arising from the right buttock
      as the only alteration, with size and shape of a lower member-like structure, and
      a pedicle of the extra limb structure. The surgical observations, the
      pathological results, evolution up to 6 months of age, and their potential causes
      are described, as well as a review of the literature. RESULTS: The MRI procedure
      also detected a multicystic mass located at the presacral region of the pelvis
      and perineum, without any dysraphism or other medullary anomalies. The X-ray
      showed that the member-like structure had an iliac wing, femur, tibia, fibula,
      and aberrant metatarsals. The review of the literature shows disparate defects of
      the published cases with HDS, which include some features pathogenically not
      related with this syndrome. CONCLUSION: We highlight the need to maintain
      restricted the clinical diagnosis for HDS to those concordant with a great
      disorganization of morphogenetic inductions affecting the three germ layers,
      which occur during the first four weeks of development. This is crucial to: (a)
      perform a correct diagnosis, which is essential to establish the prognosis and
      surgery procedures, (b) identify which is/are the cause/s, and (c) the adequate
      genetic counseling.

PMID- 24307595
TI  - A link between gut community metabolism and pathogenesis: molecular hydrogen
      stimulated glucarate catabolism aids Salmonella virulence.
AB  - Glucarate, an oxidized product of glucose, is a major serum organic acid in
      humans. Still, its role as a carbon source for a pathogen colonizing hosts has
      not been studied. We detected high-level expression of a potential glucarate
      permease encoding gene gudT when Salmonella enterica serovar Typhimurium are
      exposed to hydrogen gas (H(2)), a gaseous by-product of gut commensal metabolism.
      A gudT strain of Salmonella is deficient in glucarate-dependent growth, however,
      it can still use other monosaccharides, such as glucose or galactose.
      Complementation of the gudT mutant with a plasmid harbouring gudT restored
      glucarate-dependent growth to wild-type (WT) levels. The gudT mutant exhibits
      attenuated virulence: the mean time of death for mice inoculated with WT strain
      was 2 days earlier than for mice inoculated with the gudT strain. At 4 days
      postinoculation, liver and spleen homogenates from mice inoculated with a gudT
      strain contained significantly fewer viable Salmonella than homogenates from
      animals inoculated with the parent. The parent strain grew well H(2)-dependently
      in a minimal medium with amino acids and glucarate provided as the sole carbon
      sources, whereas the gudT strain achieved approximately 30% of the parent
      strain's yield. Glucarate-mediated growth of a mutant strain unable to produce
      H(2) was stimulated by H(2) addition, presumably owing to the positive
      transcriptional response to H(2). Gut microbiota-produced molecular hydrogen
      apparently signals Salmonella to catabolize an alternative carbon source
      available in the host. Our results link a gut microbiome-produced diffusible
      metabolite to augmenting bacterial pathogenesis.

PMID- 24307596
TI  - Continuous vagal IONM prevents recurrent laryngeal nerve paralysis by revealing
      initial EMG changes of impending neuropraxic injury: a prospective, multicenter
      study.
AB  - OBJECTIVES/HYPOTHESIS: Existing intraoperative neuromonitoring (IONM) formats
      stimulate the recurrent laryngeal nerve (RLN) intermittently, exposing it to risk
      for injury in between stimulations. We report electrophysiologic parameters of
      continuous vagal monitoring, utilizing a novel real-time IONM format, and relate
      these parameters to intraoperative surgical maneuvers that delineate nascent
      adverse but reversible electrophysiologic parameters to prevent nerve injury.
      These results are correlated with postoperative vocal cord functional outcome.
      STUDY DESIGN: Prospective multicenter tertiary study. METHOD: Evoked vagal nerve
      waveform amplitude and latency changes during 102 thyroidectomies were recorded.
      Adverse electrophysiologic response was categorized into 1-concordant amplitude
      reduction and latency increase events (combined events) and 2-loss of signal
      (LOS). Surgical maneuvers were modified when adverse electrophysiologic findings
      were noted. All patients underwent preoperative and postoperative laryngoscopy;
      intraoperative electrophysiologic findings were correlated with postoperative
      laryngeal function. RESULTS: Continuous vagal monitoring did not result in
      stimulation-evoked nerve injury or intraoperative adverse cardiac, pulmonary, or
      gastrointestinal effects. Both intraoperative combined events and LOS were
      associated with development of vocal cord paralysis (VCP) (P = 0.001 and P >0.001
      respectively). Combined events had a positive predictive value (PPV) of 33%,
      negative predictive value (NPV) of 97%, and were reversible in 73%. LOS had a PPV
      of 83%, NPV of 98%, and was reversible in only 17%. Milder combined events and
      isolated amplitude or latency changes were not associated with VCP. CONCLUSIONS:
      Continuous vagal monitoring is safe and provides real-time RLN evaluation during
      surgical maneuvers. Combined events and LOS, both easily identifiable
      intraoperatively, are related to the development of VCP. A combined event
      represents a largely reversible electrophysiologic change when the associated
      surgical maneuver is aborted. If allowed to continue, it can advance to LOS
      (which typically is significantly less reversible) and to postoperative VCP.
      Continuous vagal monitoring has utility in identifying real-time adverse
      concordant amplitude and latency changes (combined events), which can prompt
      modification of the associated surgical maneuver and may prevent RLN paralysis
      during thyroidectomy. LEVEL OF EVIDENCE: 4.

PMID- 24307598
TI  - MRI-defined height of rectal tumours.
AB  - BACKGROUND: There is no standard for reporting rectal cancer distances from the
      distal resection margin in the literature. The objective was to demonstrate the
      importance of rectal cancer measurement from a standardized point. METHODS:
      Review of databases at two international institutions identified 50 patients with
      rectal adenocarcinoma within 15 cm of the anal verge (AV), who had preoperative
      magnetic resonance imaging (MRI) and underwent surgery with curative intent.
      Expert radiologists reviewed the magnetic resonance images for anatomical
      distances from the anorectal ring (ARR) to the AV, from the ARR to the dentate
      line (DL), and from the DL to the AV. Anatomical measurements were compared with
      preoperative measurements to assess reporting inconsistencies. RESULTS: Fifty
      patients with rectal adenocarcinoma were included in the study. The mean(s.d.)
      anatomical distance was 1.66(0.61) cm from the ARR to the DL, 3.78(0.61) cm from
      the ARR to the AV (maximum 5.5 cm) and 2.11(0.10) cm from the DL to the AV. The
      mean radiological distance from the distal tumour was 2.90(1.60) (median 3.2,
      range 0-7.5) cm to the ARR, 4.36(3.20) (median 4.2, range -0.5 to 12.8) cm to the
      DL and 6.13(3.39) (median 6.0, range 0-14.1) cm to the AV. There was a
      significant difference in the distal tumour margin between measurements made by
      the expert radiologists and reported preoperative measurements (P < 0.001).
      Significant differences were also found between the expert radiologists' MRI and
      rigid proctoscopic measurements (P = 0.025). CONCLUSION: There was up to 5.5 cm
      variation, depending on which landmark was chosen for reporting the distal margin
      of rectal cancer. This has potential implications for surgical planning,
      interpreting radiological images and comparative studies.

PMID- 24307597
TI  - Extramural depth of tumor invasion at thin-section MR in rectal cancer:
      associating with prognostic factors and ADC value.
AB  - PURPOSE: To assess the value of maximal extramural depth (EMD) of T3 tumor spread
      on MRI as a potential noninvasive imaging biomarker of tumor aggressiveness in
      rectal cancer, by analyzing the relationship between tumoral EMD values and
      clinical or histological prognostic parameters. In addition, we try to
      investigate the relationship between EMD and apparent diffusion coefficient (ADC)
      values. MATERIALS AND METHODS: Ninety rectal cancer patients who underwent
      primary MRI staging and diffusion weighted imaging (DWI) as T3 tumor were
      included. Tumor EMD was measured, and the EMD values of the subgroups based on
      pretreatment CEA, CA19-9 levels, N stage, and histological parameters were
      compared. The correlation between EMD and ADC values was compared. RESULTS:
      Interobserver agreement of confidence levels for observers 1 and 2 was good for
      cN stage (k = 0.678) and EMD measurement(k = 0.612) and was excellent for ADC
      measurement (k = 0.880). Tumor EMDs differ between CEA <5 ng/mL versus >= 5 ng/mL
      (P = 0.013), CA19-9 < 27 U/mL versus >= 27 U/mL (P = 0.012), the groups of cN0
      versus cN+ cancers (P = 0.049), and between the several groups of histological
      differentiation grades (P = 0.033). There was no significant difference in EMDs
      between the various groups of vessel carcinoma embolus and neural invasion. A
      significant negative correlation (r = -0.581; P = 0.001) between ADC and EMD
      values was found. CONCLUSION: Significant correlations were found between EMD
      values and CEA, CA19-9 level, differentiation grade and ADC value. As been found,
      higher EMD values were associated with a more aggressive tumor profile and,
      therefore, EMD has the potential to become an imaging biomarker of tumor
      aggressiveness indicator.

PMID- 24307599
TI  - Extraction-free in situ derivatisation of timosaponin AIII using direct analysis
      in real time TOF/MS.
AB  - INTRODUCTION: Direct analysis in real time (DART) TOF/MS has been used for mass
      information of various non-polar phytochemicals in raw material with no sample
      preparation. However, low ionisation efficiency for polar compounds including
      glycosides limits its extensive use in the field of phytochemical analysis.
      OBJECTIVE: In order to develop a direct analysis method for polar glycosides
      using in situ derivatisation, which improves ionisation efficiency of hydrophilic
      glycosides. METHOD: Anemarrhena Rhizoma was used as a model plant targeting on
      Timosaponin AIII utilising a Dip-It module. Permethylation was applied to the
      powdered raw material with tetramethylammonium hydroxide in front of a DART ion
      source. Also, DART TOF/MS combined with permethylation was applied to timosaponin
      AIII standard solution to obtain the limit of detection (LOD). RESULTS: In situ
      methylation of timosaponin AIII and Anemarrhena Rhizoma raw material were
      successfully used to ionise the glycoside. The LOD was found to be in the range
      of 2.4-4.8 ng for permethylated timosaponin AIII and this level is four times
      higher than the range of the underivatisation analysis. Direct analysis of
      permethylated timosaponin from Anemarrhena Rhizoma was also successfully
      performed. CONCLUSION: A simple and quick derivatisation method with
      tetramethylammonium hydroxide was developed for the direct identification of a
      hydrophilic saponin from the plant tissue. Better ionisation efficiency conferred
      by in situ permethylation enabled ionisation of whole molecules of timosaponin
      AIII from the plant tissue. This simple analytical method will provide a solution
      to reduce tedious sample preparation steps, not only for non-polar but also
      hydrophilic natural products directly from the tissue.

PMID- 24307600
TI  - Application of graphene for the SPE clean-up of organophosphorus pesticides
      residues from apple juices.
AB  - In this paper, an effective graphene-based SPE clean-up procedure coupled with GC
      MS was developed for the determination of organophosphorus pesticide residues in
      apple juices. The apple juice samples were diluted with water and could be loaded
      onto the cartridge directly. Several parameters affecting the extraction
      efficiency were investigated, including the type of elution, washing solution,
      and sample pH. Under the optimized conditions, excellent limits of quantitation
      for the target analytes were found to be 0.15-1.18 ng/mL, and the average
      recoveries of the analytes at two spiked levels for real-sample analysis ranged
      from 69.8 to 106.2% with RSDs less than 7.3%. Furthermore, the graphene-based
      cartridges exhibited superior reusability for juice sample analysis. The proposed
      method is sensitive, simple, and cost saving, and provides a detection platform
      for the monitoring of pesticide residues.

PMID- 24307601
TI  - Dose enhancement by various nanoparticles in prostate brachytherapy.
AB  - The aim of this Monte Carlo study is to calculate dose enhancement in tumours by
      various nanoparticles in prostate brachytherapy using (125)I interstitial
      implants. ProstaSeed (125)I brachytherapy source was simulated using MCNPX Monte
      Carlo code. Dose rate constant, radial dose function and anisotropy function
      values were calculated and compared with previously published data. Dose
      enhancement factors (DEFs) were calculated for Fe2O3, Ag, Gd, Pt and Au
      nanoparticles with concentrations of 7, 18 and 30 mg/ml. Our source simulation
      was validated by comparing our results with previously published data. Maximum
      DEF values on the central transverse line, within the tumour, for Fe2O3, Ag, Gd,
      Pt and Au nanoparticles with 30 mg/ml concentration were 1.27, 1.15, 1.14, 1.32,
      1.79, respectively. No general trend in DEF with increasing atomic number, or
      concentration of nanoparticles was observed. However, DEF was the highest for 30
      mg/ml concentration of Au. The 50 % isodose line tightened toward the central
      point of the spherical tumour and the central 100 % isodose line expanded
      outward. The presence of nanoparticles in a prostate tumour increases the dose
      inside tumour and decreases the dose outside it, thus the treatment time and
      source activity can be decreased due to dose enhancement in the tumour. While
      more preclinical studies on other aspects are necessary, using nanoparticles can
      be proposed as a useful tool in prostate brachytherapy. Au nanoparticles with
      higher concentrations can be more useful for this purpose when compared to other
      nanoparticles.

PMID- 24307602
TI  - Salt-induced fabrication of superhydrophilic and underwater superoleophobic PAA-g
      PVDF membranes for effective separation of oil-in-water emulsions.
AB  - Conventional polymer membranes suffer from low flux and serious fouling when used
      for treating emulsified oil/water mixtures. Reported herein is the fabrication of
      a novel superhydrophilic and underwater superoleophobic poly(acrylic acid)
      grafted PVDF filtration membrane using a salt-induced phase-inversion approach. A
      hierarchical micro/nanoscale structure is constructed on the membrane surface and
      endows it with a superhydrophilic/underwater superoleophobic property. The
      membrane separates both surfactant-free and surfactant-stabilized oil-in-water
      emulsions under either a small applied pressure (<0.3 bar) or gravity, with high
      separation efficiency and high flux, which is one to two orders of magnitude
      higher than those of commercial filtration membranes having a similar permeation
      property. The membrane exhibits an excellent antifouling property and is easily
      recycled for long-term use. The outstanding performance of the membrane and the
      efficient, energy and cost-effective preparation process highlight its potential
      for practical applications.

PMID- 24307603
TI  - Different role of cAMP pathway on the human mast cells HMC-1(560) and HMC
      1(560,816) activation.
AB  - HMC-1 are inflammatory cells that release vasoactive substances such as
      histamine. These cells have the c-kit receptor permanently activated in the
      membrane due to mutations in the proto-oncogene c-kit: Val-560 -> Gly and Asp-816
      -> Val. Thus, there are two known cellular lines: HMC-1(560) and HMC-1(560,816) .
      These mutations are involved in a disease called mastocitosys. In the present
      paper both lines were used to study the influence of cAMP/PKA/PDEs pathway on the
      histamine release and Ca(2+) signaling since this pathway is often involved in
      these process. For this, the cells were preincubated with cAMP/PKA/PDEs
      modulators such as dibutyryl cAMP (dbcAMP), forskolin, H89, rolipram, IBMX, or
      imidazole and then stimulated with ionomycin. When cells were stimulated with
      agents that increase cAMP levels, the histamine release was not modified in HMC
      1(560) but decreased in HMC-1(560,816) cells. The same happened when PKA was
      blocked. Furthermore, PDEs role on histamine release was independent of cAMP in
      HMC-1(560) cells and possibly also in HMC-1(560,816) cells. By contrast, the
      modulation of PKA and PDEs together changed the response in both cellular lines,
      therefore a relationship between them was suggested. All these modulatory effects
      on histamine release are Ca(2+) -independent. On the other hand, the effect of c
      kit modulation on the cAMP/PKA/PDEs pathway was also checked. This receptor was
      blocked with STI571 (imatinib) and BMS-354825 (dasatinib), but only the last one
      caused a decrease in the cellular response to ionomycin. This article
      demonstrates for the first time than the cAMP/PKA/PDEs pathway is involved in the
      activation of HMC-1(560) and HMC-1(560,816) cells.

PMID- 24307604
TI  - Cranial nerve assessment: a concise guide to clinical examination.
AB  - Examination of the cranial nerves is an integral and important part of a complete
      neurological examination. Historically, these skills were crucial for diagnosing
      specific lesions. With the development of modern imaging modalities, the
      significance of clinical examination techniques has perhaps been undermined. The
      authors present an overview of each cranial nerve with a concise summary of
      examination techniques.

PMID- 24307605
TI  - Development and comparison of new high-efficiency dry powder inhalers for carrier
      free formulations.
AB  - High-efficiency dry powder inhalers (DPIs) were developed and tested for use with
      carrier-free formulations across a range of different inhalation flow rates.
      Performance of a previously reported DPI was compared with two new designs in
      terms of emitted dose (ED) and aerosolization characteristics using in vitro
      experiments. The two new designs oriented the capsule chamber (CC) at different
      angles to the main flow passage, which contained a three-dimensional (3D) rod
      array for aerosol deaggregation. Computational fluid dynamics simulations of a
      previously developed deaggregation parameter, the nondimensional specific
      dissipation (NDSD), were used to explain device performance. Orienting the CC at
      90 degrees  to the mouthpiece, the CC90 -3D inhaler provided the best performance
      with an ED = 73.4%, fine particle fractions (FPFs) less than 5 and 1 MUm of 95.1%
      and 31.4%, respectively, and a mass median aerodynamic diameter (MMAD) = 1.5 MUm.
      For the carrier-free formulation, deaggregation was primarily influenced by
      capsule aperture position and the NDSD parameter. The new CC-3D inhalers reduced
      the percent difference in FPF and MMAD between low and high flows by 1-2 orders
      of magnitude compared with current commercial devices. In conclusion, the new CC
      3D inhalers produced extremely high-quality aerosols with little sensitivity to
      flow rate and are expected to deliver approximately 95% of the ED to the lungs.

PMID- 24307608
TI  - Second study on the recurrence risk of isolated esophageal atresia with or
      without trachea-esophageal fistula among first-degree relatives: no evidence for
      increased risk of recurrence of EA/TEF or for malformations of the VATER/VACTERL
      association spectrum.
AB  - BACKGROUND: Esophageal atresia with/without trachea-esophageal fistula (EA/TEF)
      denotes a spectrum of severe congenital malformations. The aim of this systematic
      study was to determine both the recurrence risk for EA/TEF, and the risk for
      malformations of the VATER/VACTERL association spectrum, in first-degree
      relatives of patients with isolated EA/TEF. METHODS: A total of 108 unrelated
      patients with isolated EA/TEF were included. These individuals had 410 first
      degree relatives including 194 siblings. The presence of EA/TEF and malformations
      of the VATER/VACTERL association spectrum in relatives was systematically
      assessed. Data from the EUROCAT network were used for comparison. RESULTS: None
      of the first-degree relatives displayed any form of EA/TEF. In two families, a
      first-degree relative presented with malformations from the VATER/VACTERL
      association spectrum. However, no increase in the risk for malformations of the
      VATER/VACTERL association spectrum was found compared with the control cohort (p
      = 0.87). In three families, one more distantly related relative presented with
      EA/TEF. CONCLUSION: In contrast to previous studies, our results suggest a very
      low recurrence risk for isolated EA/TEF and/or for malformations of the
      VATER/VACTERL association spectrum among first-degree relatives.

PMID- 24307609
TI  - Blood pressure response to renal artery stenting in 901 patients from five
      prospective multicenter FDA-approved trials.
AB  - BACKGROUND: Renal artery stent revascularization is commonly used for
      renovascular hypertension. Clinical predictors associated with blood pressure
      (BP) improvement after renal artery stent revascularization are not well
      understood. METHODS: Patient-level data from 901 patients in five prospective
      multicenter Food and Drug Administration-approved investigational device
      exemption studies of renal artery stent revascularization was pooled. BP response
      was defined as reduction of systolic BP (SBP) by >10 mm Hg. Stent patency was
      defined within each study. Associations of BP reduction were determined by
      logistic regression. RESULTS: Of 901 patients, complete outcome information was
      available in 527. Of these, 212/527 (40%) were male, mean age was 63 +/- 13
      years, 196/544 (36%) were diabetic and 504/527 (96%) had a SBP >= 140 mm Hg or
      DBP >= 90 mm Hg at baseline. Compared to baseline, 9-month systolic (164 +/- 21
      mm Hg vs. 146 +/- 22 mm Hg, P < 0.0001) and diastolic (79 +/- 13 mm Hg vs. 76 +/-
      12 mm Hg, P < 0.0001) BP declined significantly. Nine-month stent patency was 90%
      (305/339). In a univariate analysis, baseline SBP >150 mm Hg (OR = 4.09, CI =
      2.74-6.12, P < 0.0001) was positively associated with BP response following renal
      artery stent revascularization. In a multivariable analysis, baseline SBP
      remained associated with a positive BP response (OR = 1.76, CI = 1.53-2.03, P <
      0.0001). CONCLUSIONS: In the largest pooled dataset of patients treated with
      renal artery stent revascularization, SBP and DBP were significantly lower at 9
      months. Elevated baseline SBP (>150 mm Hg) was strongly associated with BP
      reduction after the procedure.

PMID- 24307610
TI  - Plant phytochemicals as epigenetic modulators: role in cancer chemoprevention.
AB  - In recent years, "nutri-epigenetics," which focuses on the influence of dietary
      agents on epigenetic mechanism(s), has emerged as an exciting novel area in
      epigenetics research. Targeting of aberrant epigenetic modifications has gained
      considerable attention in cancer chemoprevention research because, unlike genetic
      changes, epigenetic alterations are reversible and occur during early
      carcinogenesis. Aberrant epigenetic mechanisms, such as promoter DNA methylation,
      histone modifications, and miRNA-mediated post-transcriptional alterations, can
      silence critical tumor suppressor genes, such as transcription factors, cell
      cycle regulators, nuclear receptors, signal transducers, and apoptosis-inducing
      and DNA repair gene products, and ultimately contribute to carcinogenesis. In an
      effort to identify and develop anticancer agents which cause minimal harm to
      normal cells while effectively killing cancer cells, a number of naturally
      occurring phytochemicals in food and medicinal plants have been investigated.
      This review highlights the potential role of plant-derived phytochemicals in
      targeting epigenetic alterations that occur during carcinogenesis, by modulating
      the activity or expression of DNA methyltransferases, histone modifying enzymes,
      and miRNAs. We present in detail the epigenetic mode of action of various
      phytochemicals and discuss their potential as safe and clinically useful
      chemopreventive strategies. 

PMID- 24307611
TI  - Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to
      hair follicles and human dermal papilla cells.
AB  - Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related
      cells is important in the treatment of alopecia. Here we report the development
      of "squarticles," nanoparticles formed from sebum-derived lipids such as squalene
      and fatty esters, for use in achieving targeted drug delivery to the follicles.
      Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions
      (NE), were prepared. The physicochemical properties of squarticles, including
      size, zeta potential, drug encapsulation efficiency, and drug release, were
      examined. Squarticles were compared to a free control solution with respect to
      skin absorption, follicular accumulation, and dermal papilla cell targeting. The
      particle size of the NLC type was 177 nm; that of the NE type was 194 nm.
      Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles.
      An improved drug deposition in the skin was observed in the in vitro absorption
      test. Compared to the free control, the squarticles reduced minoxidil penetration
      through the skin. This may indicate a minimized absorption into systemic
      circulation. Follicular uptake by squarticles was 2- and 7-fold higher for DPCP
      and minoxidil respectively compared to the free control. Fluorescence and
      confocal images of the skin confirmed a great accumulation of squarticles in the
      follicles and the deeper skin strata. Vascular endothelial growth factor
      expression in dermal papilla cells was significantly upregulated after the
      loading of minoxidil into the squarticles. In vitro papilla cell viability and in
      vivo skin irritancy tests in nude mice suggested a good tolerability of
      squarticles to skin. Squarticles provide a promising nanocarrier for topical
      delivery of DPCP and minoxidil. 

PMID- 24307612
TI  - Neutrophil-to-lymphocyte ratio as a novel-potential marker for predicting
      prognosis of Bell palsy.
AB  - OBJECTIVES/HYPOTHESIS: Bell palsy can be defined as an idiopathic, acute, facial
      nerve palsy. Although the pathogenesis of Bell palsy is not fully understood,
      inflammation seems to play important role. Neutrophil-to-lymphocyte (NLR) ratio
      was defined as a novel potential marker to determine inflammation and it is
      routinely measured in peripheral blood. Our goal was to investigate the
      relationship between Bell palsy and inflammation by using NLR. STUDY DESIGN:
      Retrospective study. METHODS: The 54 patients who were followed up for Bell palsy
      for a period of 1 to 3 years, along with 45 age- and sex-matched controls, were
      included in the study. An automated blood cell counter was used for NLR
      measurements. All patients were treated with prednisone, 1 mg/kg per day with a
      progressive dose reduction. Patients were classified according to the House
      Brackmann grading system at posttreatment period. Those with House-Brackmann
      grade I and grade II were regarded as satisfactory recovery; and those with House
      Brackmann grade III to grade VI were regarded as nonsatisfactory recovery.
      RESULTS: The mean NLR and neutrophil values in patients with Bell palsy were
      significantly higher than in the control group (P=0.001 and P<0.001,
      respectively). In addition, NLR levels were higher in nonsatisfactory recovered
      patients compared with satisfactory recovered ones (P<0.001). CONCLUSION: This is
      the first study investigating the relationship between NLR levels and Bell palsy
      and its prognosis. Our result suggest that while evaluating Bell palsy patients,
      NLR might be taken into account as a novel potential marker to predict the
      patients' prognosis. LEVEL OF EVIDENCE: 3b.

PMID- 24307613
TI  - Editorial: microbial interactions in the rhizosphere.

PMID- 24307616
TI  - Stereochemistry of C18 monounsaturated cork suberin acids determined by
      spectroscopic techniques including (1) H-NMR multiplet analysis of olefinic
      protons.
AB  - INTRODUCTION: Suberin is a biopolyester responsible for the protection of
      secondary plant tissues, and yet its molecular structure remains unknown. The
      C18:1 omega-hydroxyacid and the C18:1 alpha,omega-diacid are major monomers in
      the suberin structure, but the configuration of the double bond remains to be
      elucidated. OBJECTIVE: To unequivocally define the configuration of the C18:1
      suberin acids. METHODS: Pure C18:1 omega-hydroxyacid and C18:1 alpha,omega
      diacid, isolated from cork suberin, and two structurally very close C18:1 model
      compounds of known stereochemistry, methyl oleate and methyl elaidate, were
      analysed by NMR spectroscopy, Fourier transform infrared (FTIR) and Raman
      spectroscopy, and GC-MS. RESULTS: The GC-MS analysis showed that both acids were
      present in cork suberin as only one geometric isomer. The analysis of
      dimethyloxazoline (DMOX) and picolinyl derivatives proved the double bond
      position to be at C-9. The FTIR spectra were concordant with a cis-configuration
      for both suberin acids, but their unambiguous stereochemical assignment came from
      the NMR analysis: (i) the chemical shifts of the allylic (13) C carbons were
      shielded comparatively to the trans model compound, and (ii) the complex
      multiplets of the olefinic protons could be simulated only with (3) JHH and long
      range (4) JHH coupling constants typical of a cis geometry. CONCLUSION: The two
      C18:1 suberin acids in cork are (Z)-18-hydroxyoctadec-9-enoic acid and (Z)
      octadec-9-enedoic acid.

PMID- 24307618
TI  - Deception of children in research.
AB  - The aim of this article is to draw attention to an under-recognised but ethically
      important phenomenon involving the deception of children in research. The type of
      deception we are referring to is not planned deception that is part of the
      research design. Instead it is deception that occurs in individual cases where
      parents ask researchers not to reveal something about the research to their
      child. Our focus is children who do not have ultimate decisional authority-
      children around the ages of 7-14 years old who may have the cognitive capacity to
      understand but not to consent for themselves; children whose agreement is
      required but not sufficient to authorise research. We provide three illustrative
      scenarios for analysis. Then, we identify circumstances in which non-disclosure
      might be justified and set out reasons why providing information to non-competent
      children is ethically required. On this basis, we argue that non-planned
      deception requested by parents is very unlikely to be ethically acceptable.
      Finally, we recommend that guidelines should (a) require researchers to consider
      what to do if parents do not want to disclose information to a child and (b)
      clarify that the most ethical response is to simply not include that child in the
      research.

PMID- 24307619
TI  - The Val158Met polymorphism in the COMT gene is associated with increased cancer
      risks in Chinese population.
AB  - The Val158Met polymorphism in the COMT gene may affect the DNA repair pathways
      and be associated with the risk of cancer in Chinese population. However, the
      results of previous studies are inconsistent. The objective of this study was to
      investigate the association between the Val158Met polymorphism in the COMT gene
      and the risk of cancer for Chinese population by meta-analysis. We searched
      PubMed, Embase, CNKI, Weipu, and Wanfang databases, and the last search was
      updated on Sep. 26, 2013. Statistical analysis was performed using the Revman4.2
      and Stata10.0 software. A total of 18 case-control studies concerning 5034 case
      and 6234 controls were included. In the total analysis, the results suggested a
      significant association between the Val158Met polymorphism in the COMT gene and
      the cancer risk in Chinese population: OR = 1.34, 95%CI = 1.04-1.73, and P = 0.03
      for AA vs. AG + GG; OR = 1.39, 95%CI = 1.06-1.82, and P = 0.02; OR = 1.13, 95%CI
      = 1.01-1.27, and P = 0.04. In the subgroup analysis by cancer types, significant
      association was found in the breast cancer and esophageal squamous cell
      carcinoma. The current meta-analysis confirmed that the Val158Met polymorphism in
      the COMT gene may be a risk factor for cancer in Chinese population. In the
      future, more case-control studies are needed to validate our results.

PMID- 24307620
TI  - Breast cancer sentinel lymph node mapping using near-infrared guided indocyanine
      green in comparison with blue dye.
AB  - Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) was
      considered to have the potential to improve sentinel lymph node (SLN) mapping in
      breast cancer. Herein, we performed a randomized clinical trial to evaluate the
      effectiveness of ICG fluorescence imaging compared with blue dye imaging in SLN
      navigation surgery. We also analyzed lymph drainage pathways to identify targets
      for sentinel lymph node biopsy (SLNB). Finally, 68 consecutive patients diagnosed
      with breast cancer and who underwent SLNB between November 2010 and September
      2012 were enrolled in the study. The cases were randomly grouped into either the
      ICG fluorescence or blue dye group, with 36 in the ICG fluorescence group and 32
      in the blue dye group. Levels I and II axillary dissection was performed in all
      cases after SLNB. A single lymph drainage pathway was detected in 21 of 36
      (58.3%) patients, and multiple lymph drainage pathways were detected in 15 of 36
      (41.7%) cases. The detection rate of SLNB was higher by ICG fluorescence than by
      blue dye (97.2 vs. 81.3%, p < 0.05), as 3.6 SLNs were detected on average in the
      ICG fluorescence group compared to 2.1 in the blue dye group. However, the
      sensitivity and false-negative rate were similar in the two groups. In
      conclusion, ICG fluorescence was superior to blue dye for the identification of
      the SLN.

PMID- 24307621
TI  - Clinical significance of serum epithelial cell adhesion molecule (EPCAM) and
      vascular cell adhesion molecule-1 (VCAM-1) levels in patients with epithelial
      ovarian cancer.
AB  - Cellular adhesion molecules might be good markers in some types of malignant
      tumors, useful information in diagnosis and prognosis. The objective of this
      study was to evaluate the serum levels of epithelial cell adhesion molecule
      (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) in epithelial ovarian
      cancer (EOC) patients. Fifty patients were enrolled into the study. Serum EPCAM
      and VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Age-
      and sex-matched 30 healthy controls were included in the analysis. The median age
      of the patients was 56.5 years, range 22 to 83 years. Majority of the patients
      had advanced disease (stages III-IV) (90%). The baseline serum EPCAM levels of
      the EOC patients were significantly higher than in those in the control group (p
      = 0.03). However, there was no significant difference in the serum VCAM-1 level
      between EOC patients and controls (p = 0.24). Metastatic patients had higher
      serum VCAM-1 levels compared with the non-metastatic patients (p = 0.03).
      Moreover, no other clinical variables including response to chemotherapy were
      found to be correlated with both serum assays (p > 0.05). No correlation was
      found between serum EPCAM and VCAM-1 levels in EOC patients (r(s) = 0.105, p =
      0.362). Neither serum EPCAM level nor serum VCAM-1 level had significant adverse
      effect on survival. In conclusion, the higher baseline serum levels of VCAM-1
      were associated with metastatic disease, and serum EPCAM level was found to be a
      diagnostic marker in EOC patients. However, both serum assays had no prognostic
      roles on outcome.

PMID- 24307622
TI  - CCNG2 expression is downregulated in colorectal carcinoma and its clinical
      significance.
AB  - This study aimed to analyze the expression, clinical significance of cyclin G2
      (CCNG2) in colorectal carcinoma, and the biological effect in its cell line by
      CCNG2 overexpression. Immunohistochemistry and Western blot were used to analyze
      CCNG2 protein expression in colorectal cancer and to study the influence of the
      upregulated expression of CCNG2 that might be found on SW480 cell biological
      effect. We found that the level of CCNG2 protein expression was significantly
      lower in colorectal cancer tissue than normal tissues (P < 0.05). The level of
      CCNG2 was correlated with T stages, lymph node metastasis, clinic stage, and
      histological grade (P < 0.05). Loss of CCNG2 expression correlated significantly
      with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result
      of biological function has shown that SW480 cell-transfected CCNG2 had a lower
      survival fraction, higher percentage of the G0/G1 phases, and lower CDK2 protein
      expression compared with SW480 cell-untransfected CCNG2 (P < 0.05).

PMID- 24307623
TI  - Association between the CYP1A1 A2455G polymorphism and risk of cancer: evidence
      from 272 case-control studies.
AB  - A2455G is a common polymorphism in CYP1A1, showing differences in its biological
      functions. Case-control studies have been performed to elucidate the role of
      A2455G in cancer; however, the results are conflicting and heterogeneous. Hence,
      we performed a meta-analysis to investigate the association between cancer
      susceptibility and A2455G (64,593 cases and 91,056 controls from 272 studies)
      polymorphism in different inheritance models. We used odds ratios with 95%
      confidence intervals to assess the strength of the association. Overall,
      significantly increased cancer risk was observed in any genetic model (dominant
      model, odds ration [OR] = 1.19, 95% confidence interval [CI] = 1.13-1.25;
      recessive model: OR = 1.41, 95% CI = 1.29-1.54; additive model: OR = 1.49, 95% CI
      = 1.35-1.65) when all eligible studies were pooled into the meta-analysis. In
      further stratified and sensitivity analyses, the elevated risk remained for
      subgroups of breast cancer, colorectal cancer, esophageal cancer, hepatocellular
      cancer, head and neck cancer, leukemia, lung cancer, and prostate cancer, but
      these associations vary in different ethnic populations. In summary, this meta
      analysis suggests the participation of A2455G in the susceptibility for some
      cancers, such as breast cancer, colorectal cancer, lung cancer, and so on.
      Moreover, ethnicity, histological type of cancer, and smokers seem to contribute
      to varying expressions of the A2455G on some cancers risk. In addition, our work
      also points out the importance of new studies for A2455G polymorphism in some
      cancer types, such as gallbladder cancer, Indians of breast cancer, and
      Caucasians of ovarians, because these cancer types had high heterogeneity in this
      meta-analysis (I(2) > 75%).

PMID- 24307624
TI  - VEGF-C expression is associated with the poor survival in gastric cancer tissue.
AB  - Vascular endothelial growth factor-C (VEGF-C) is considered as a prime mediator
      of lymphangiogenesis and has been implicated in carcinogenesis and metastasis.
      Various studies examined the relationship between VEGF-C overexpression and the
      clinical outcome in patients with gastric cancer, but yielded conflicting
      results. Electronic databases updated to July 2013 were searched to find relevant
      studies. A meta-analysis was conducted with eligible studies which quantitatively
      evaluated the relationship between VEGF-C overexpression and survival of patients
      with gastric cancer. Survival data were aggregated and quantitatively analyzed.
      We performed a meta-analysis of 13 studies that evaluated the correlation between
      VEGF-C overexpression and survival in patients with gastric cancer. Combined
      hazard ratios suggested that VEGF-C overexpression had an unfavorable impact on
      overall survival (OS) (hazard ratio (HR) = 1.38, 95% confidence interval (CI) =
      1.08-1.68), but not disease-free survival (DFS) (HR = 1.25, 95% CI = 0.89-1.62)
      in patients with gastric cancer. No significant heterogeneity (P = 0.132) was
      observed among 11 studies for OS and among 5 studies for DFS (P = 0.105). VEGF-C
      overexpression indicates a poor prognosis for overall survival, but not disease
      free survival in patients with gastric cancer.

PMID- 24307625
TI  - Haplotype-based case-control study of DNA repair gene XRCC3 and hepatocellular
      carcinoma risk in a Chinese population.
AB  - Previous studies indicated that the human X-ray repair complementing group 3 gene
      (XRCC3) plays an important role in hepatocellular carcinoma (HCC) susceptibility.
      We aimed to investigate the association of XRCC3 genetic polymorphism with HCC
      risk. This study was conducted in a Chinese Han population consisting of 300 HCC
      cases and 300 sex- and age-matched cancer-free controls. Three genetic variants
      (rs861539, rs12432907, and rs861537) were genotyped by the TaqMan(r) SNP
      Genotyping Assay. Our findings suggested that the TT genotype and T allele from
      rs861539 genetic variants were statistically associated with HCC risk. The TT
      genotype was statistically associated with the increased risk of HCC compared to
      CC wild genotype (P < 0.001). And the T allele was more common in the HCC
      patients than that in the control subjects. (OR = 1.97, 95% confidence interval
      (CI) 1.457 ~ 2.659, P < 0.001). Haplotype-based case-control study analysis
      indicated that TTG haplotype was more frequent in HCC groups than in the control
      group (odds ratio (OR) = 1.967, 95% CI 1.456 ~ 2.658); however, the CTG haplotype
      is more common in the control group than that in the HCC group (OR = 0.550, 95 %
      CI 0.430 ~ 0.703; P < 0.001). Our data indicated that genetic variants of the
      XRCC3 gene were statistically associated with HCC risk in a Chinese population.

PMID- 24307626
TI  - Meta-analysis: eating frequency and risk of colorectal cancer.
AB  - Eating frequency has been implicated in the risk of colorectal cancer (CRC) in
      several epidemiological studies with contradictory and inconclusive findings. We
      performed a meta-analysis to evaluate their relationship. The pooled relative
      risk (RR) with 95% confidence interval (CI) was calculated to estimate the
      effects. A total of 15 eligible studies with 141,431 subjects and 11,248 cases
      were retrieved after a comprehensive search of the PubMed, Cochrane Library, and
      Web of Science databases up to October 2013. The overall meta-analysis revealed
      no strong significant association between eating frequency and risk of CRC in
      different eating occasion categories (1 meal/day): RR = 1.01, 95% CI 0.94-1.09, P
      = 0.709; 3 vs. <3 daily meals: RR = 1.17, 95% CI 0.93-1.46; 4 vs. <3 daily meals:
      RR = 1.13, 95% CI 0.92-1.38; >= 5 vs. <3 daily meals: RR = 0.95, 95% CI 0.61
      1.47; 4 vs. <= 3 daily meals: RR = 1.18, 95% CI 0.92-1.51; and 1-2 vs. 3 or 4
      daily meals: RR = 0.82, 95% CI 0.63-1.06). However, modest evidence of an
      increased risk of CRC in case-control studies (RR = 1.30; 95% CI, 1.11-1.52) and
      >= 5 vs. <= 3 meals group (RR = 1.30; 95% CI, 1.11-1.52) was observed. Our meta
      analysis results do not support the hypothesis that eating frequency strongly
      reduced or increased the risk of CRC. Clinical randomized trials are required to
      evaluate this relationship further.

PMID- 24307628
TI  - Carbon dioxide capture and use: organic synthesis using carbon dioxide from
      exhaust gas.
AB  - A carbon capture and use (CCU) strategy was applied to organic synthesis. Carbon
      dioxide (CO2) captured directly from exhaust gas was used for organic
      transformations as efficiently as hyper-pure CO2 gas from a commercial source,
      even for highly air- and moisture-sensitive reactions. The CO2 capturing aqueous
      ethanolamine solution could be recycled continuously without any diminished
      reaction efficiency.

PMID- 24307627
TI  - Association between cytotoxic T lymphocyte antigen-4 +49A/G, -1722T/C, and 
      1661A/G polymorphisms and cancer risk: a meta-analysis.
AB  - Cytotoxic T lymphocyte antigen-4 (CTLA-4), a key gene that contributes to the
      susceptibility and clinical course of cancer, is an important down-regulator of T
      cell activation and proliferation. The +49A/G polymorphism is commonly studied
      because of its association with cancer risks. However, other polymorphisms, such
      as -1722T/C and -1661A/G, have not been studied in detail. We performed a meta
      analysis using 43 eligible case-control studies with a total of 19,089 patients
      and 21,388 controls to examine the association between CTLA-4 +49A/G, -1722T/C,
      and -1661A/G polymorphisms and cancer risk. We searched the PubMed and EMBASE
      databases for all articles published up to July 17, 2013. Individuals with the
      +49 A allele (AA/AG vs. GG, odds ratio (OR) = 1.21, 95% confidence interval (95%
      CI) = 1.16-1.27) and -1661 G allele (AG/GG vs. AA, OR = 1.52, 95% CI = 1.34-1.73)
      had increased cancer risk. However, no significant association between cancer
      risk and the -1722T/C polymorphism was found (CC/CT vs. TT, OR = 1.04, 95% CI =
      0.92-1.16). In subgroup analysis for the +49A/G polymorphism, increased cancer
      risk remained in the subgroups of Asians (OR = 1.25, 95 % CI = 1.18-1.31),
      patients with breast cancer (OR = 1.28, 95% CI = 1.15-1.42), and patients with
      lung cancer (OR = 1.20, 95 % CI = 1.07-1.35). For the -1661A/G polymorphism,
      increased cancer risk remained in the subgroups of Asians (OR = 1.52, 95% CI =
      1.34-1.73), patients with breast cancer (OR = 1.48, 95% CI = 1.07-2.03), and
      patients with oral cancer (OR = 3.16, 95% CI = 1.84-5.45). However, no
      significant increase in cancer risk was found in the subgroups for the -1722T/C
      polymorphism. In conclusion, the results suggest that +49A/G and -1661A/G
      polymorphisms in CTLA-4 are risk factors for cancers, whereas the -1722T/C
      polymorphism is not associated with an increased risk of cancer.

PMID- 24307630
TI  - Zebrafish as a model system to study toxicology.
AB  - Monitoring and assessing the effects of contaminants in the aquatic eco
      environment is critical in protecting human health and the environment. The
      zebrafish has been widely used as a prominent model organism in different fields
      because of its small size, low cost, diverse adaptability, short breeding cycle,
      high fecundity, and transparent embryos. Recent studies have demonstrated that
      zebrafish sensitivity can aid in monitoring environmental contaminants,
      especially with the application of transgenic technology in this area. The
      present review provides a brief overview of recent studies on wild-type and
      transgenic zebrafish as a model system to monitor toxic heavy metals, endocrine
      disruptors, and organic pollutants for toxicology. The authors address the new
      direction of developing high-throughput detection of genetically modified
      transparent zebrafish to open a new window for monitoring environmental
      pollutants.

PMID- 24307631
TI  - Big bubble DALK after CXL in keratoconic patients.

PMID- 24307629
TI  - Novel insights into embryonic stem cell self-renewal revealed through comparative
      human and mouse systems biology networks.
AB  - Embryonic stem cells (ESCs), characterized by their ability to both self-renew
      and differentiate into multiple cell lineages, are a powerful model for
      biomedical research and developmental biology. Human and mouse ESCs share many
      features, yet have distinctive aspects, including fundamental differences in the
      signaling pathways and cell cycle controls that support self-renewal. Here, we
      explore the molecular basis of human ESC self-renewal using Bayesian network
      machine learning to integrate cell-type-specific, high-throughput data for gene
      function discovery. We integrated high-throughput ESC data from 83 human studies
      (~1.8 million data points collected under 1,100 conditions) and 62 mouse studies
      (~2.4 million data points collected under 1,085 conditions) into separate human
      and mouse predictive networks focused on ESC self-renewal to analyze shared and
      distinct functional relationships among protein-coding gene orthologs.
      Computational evaluations show that these networks are highly accurate,
      literature validation confirms their biological relevance, and reverse
      transcriptase polymerase chain reaction (RT-PCR) validation supports our
      predictions. Our results reflect the importance of key regulatory genes known to
      be strongly associated with self-renewal and pluripotency in both species (e.g.,
      POU5F1, SOX2, and NANOG), identify metabolic differences between species (e.g.,
      threonine metabolism), clarify differences between human and mouse ESC
      developmental signaling pathways (e.g., leukemia inhibitory factor (LIF)
      activated JAK/STAT in mouse; NODAL/ACTIVIN-A-activated fibroblast growth factor
      in human), and reveal many novel genes and pathways predicted to be functionally
      associated with self-renewal in each species. These interactive networks are
      available online at www.StemSight.org for stem cell researchers to develop new
      hypotheses, discover potential mechanisms involving sparsely annotated genes, and
      prioritize genes of interest for experimental validation.

PMID- 24307632
TI  - Validation of congenital anomaly coding in Canada's administrative databases
      compared with a congenital anomaly registry.
AB  - BACKGROUND: Congenital anomaly (CA) surveillance provides epidemiologic data that
      are necessary for health planning. Approaches to CA surveillance vary; however,
      an increasing number of jurisdictions rely on administrative health databases for
      case ascertainment. This study aimed to assess the validity of CA coding in three
      administrative databases compared with a CA registry. METHODS: A cohort of 5862
      live and stillborn infants from Calgary Alberta Canada was created through
      linking 12 clinical and administrative databases. Diagnostic codes for all health
      care contacts (hospitalizations, emergency room visits, out-patient physician
      visits) in the first 3 months of life were examined for relevant International
      Classification of Disease codes. Sensitivity, positive predictive values, and
      kappa coefficients were calculated, and data from the Alberta Congenital
      Anomalies Surveillance System was used as the reference standard. RESULTS: The
      ability of administrative data to accurately ascertain CAs varied by data source
      and the specificity of the diagnosis. Consistently, hospitalization data out
      performed other administrative data sources in terms of sensitivity, positive
      predictive values, and kappa. Kappa scores for CAs easily visible at birth ranged
      from moderate (0.62 for emergency room visits and 0.65 for out-patient physician
      claims) to good (0.83 for hospitalization data) depending on the data source.
      CONCLUSION: The validity of CA coding in administrative databases compared with a
      CA registry varies by database used and by CA studied. This has important
      implications for national surveillance efforts. Condition-specific validity
      should be assessed locally before use of these data sources for research or
      planning purposes.

PMID- 24307633
TI  - Prolonged efficiency of siRNA-mediated gene silencing in primary cultures of
      human preadipocytes and adipocytes.
AB  - OBJECTIVE: Primary human preadipocytes and differentiated adipocytes in culture
      are valuable cell culture systems to study adipogenesis and adipose function in
      relation to human adipose biology. To use these systems for mechanistic studies,
      siRNA-mediated knockdown of genes for its effectiveness was studied. METHODS:
      Methods were developed to effectively deliver siRNA for gene silencing in primary
      preadipocytes isolated from human subcutaneous adipose tissue and newly
      differentiated adipocytes. Expression level of genes and proteins was measured
      using quantitative RT-PCR and western blotting. Lipid droplet morphology was
      observed using microscopy, and glycerol release was quantified as a measure of
      lipolysis. RESULTS: siRNA-mediated knockdown of genes in primary human
      preadipocytes resulted in prolonged silencing effects, suppressing genes
      throughout the process of their differentiation. In newly differentiated
      adipocytes, siRNA-mediated gene knockdown allowed proteins to stay depleted for
      at least 5 days. It was possible to re-express a protein after its siRNA-mediated
      depletion. Importantly, siRNA transfected human adipocytes remained metabolically
      active, responding to beta-adrenergic stimulation to increase lipolysis.
      CONCLUSIONS: Our study describes the methods of gene silencing in primary
      cultures of human preadipocytes and adipocytes and their prolonged effectiveness.

PMID- 24307634
TI  - The real world experience of the biodegradable polymer-coated sirolimus-eluting
      coronary stent system: Results From an "All-Comers" Clinical Experience.
AB  - OBJECTIVES: This INDOLIMUS Registry sought to evaluate the safety and efficacy of
      the biodegradable polymer coated Indolimus((r)) sirolimus-eluting coronary stent
      for the treatment of coronary artery disease across a wide range of patients
      treated in routine clinical practice, including those with high-risk
      characteristics and complex lesions. BACKGROUND: First-generation drug-eluting
      stents utilize nonbiodegradable polymeric coatings, whose persistent presence in
      the arterial wall may negatively affect long-term outcomes. It has been
      hypothesized that persistent presence of polymer may compromise the safety of
      drug-eluting stents, and that therefore biodegradable polymer coatings might
      reduce late adverse events in an unselected patient population. METHODS: All 530
      consecutive unselected patients (415 males and 115 females) included who
      underwent percutaneous coronary intervention at the Sri Venkateswara Institute of
      Medical Sciences, Tirupati, India between August 2012 and March 2013, with an in
      hospital, at 30-days and at 6-months follow-up. Retrospective analysis of those
      data had been done. RESULTS: A total of 617 lesions were treated in 530 enrolled
      patients (mean age 54.9 +/- 10.8 years) with average stent length of 18.8 +/- 6.0
      mm. An average of 1.18 stents was implanted per patient. The patients'
      characteristics are noted as having 169 (31.9%) patients of diabetics and 215
      (40.6%) hypertension. Smoking, alcoholism and tobacco chewing were found in 273
      (51.5%), 130 (24.5%) and 17 (3.2%), respectively. The indications for
      intervention were unstable angina in 77 (14.5%) and previous myocardial
      infarction in 56 (10.6%) of the patients. Lesions were of type B2 in 264 (42.7%)
      and type C in 127 (20.6%). Stent delivery was successful in all cases and in
      hospital, 30-days and 6-months follow-up of all 530 patients was obtained. The
      incidence of any major adverse cardiac events at in-hospital, at 30-days and at 6
      months were 5 (0.94%), 8 (1.52%), and 18 (3.40%), respectively. Long term follow
      up of this registry is ongoing to confirm safety and efficacy profiles.
      CONCLUSIONS: The relatively low event rate that was observed in INDOLIMUS
      Registry indicates that the biodegradable polymer coated Indolimus((r)) sirolimus
      eluting coronary stent can achieve excellent clinical performances in a large
      group of patients. (c) 2013 Wiley Periodicals, Inc.

PMID- 24307636
TI  - Three versus five micrometer chlorinated polysaccharide-based packings in chiral
      capillary electrochromatography: efficiency and precision evaluation.
AB  - In an earlier part of this study (performance evaluation) it was observed, for
      home-made capillary electrochromatography (CEC) columns, that smaller particle
      diameters do not always generate higher efficiencies. This phenomenon was further
      examined in this study, evaluating Van Deemter curves. Naphthalene and trans
      stilbene oxide were analyzed on four 3 um and four 5 um chlorinated
      polysaccharide-based chiral stationary phases (CSPs) applying voltages ranging
      from 5 to 30 kV. Neither the 3 nor the 5 um packings generated systematically the
      highest efficiencies. The varying column efficiencies were optimized by
      evaluating nine packing procedures for both 3 and 5 um CSPs. Again it was
      observed that smaller particle-size packings were not necessarily beneficial for
      the efficiency of the CEC analysis. This observation was statistically evaluated.
      A variability study evaluated different precision estimates related to column
      packing and replicate measurement conditions. The best columns with the highest
      efficiencies (for chiral separations) and good precision, that is, the lowest RSD
      values, were generated by the packing procedure in which an MeOH-slurry and a
      water rinsing step of 8 h were applied.

PMID- 24307635
TI  - Comparative proteomics reveals key proteins recruited at the nucleoid of
      Deinococcus after irradiation-induced DNA damage.
AB  - The nucleoids of radiation-resistant Deinococcus species show a high degree of
      compaction maintained after ionizing irradiation. We identified proteins
      recruited after irradiation in nucleoids of Deinococcus radiodurans and
      Deinococcus deserti by means of comparative proteomics. Proteins in nucleoid
      enriched fractions from unirradiated and irradiated Deinococcus were identified
      and semiquantified by shotgun proteomics. The ssDNA-binding protein SSB, DNA
      gyrase subunits GyrA and GyrB, DNA topoisomerase I, RecA recombinase, UvrA
      excinuclease, RecQ helicase, DdrA, DdrB, and DdrD proteins were found in
      significantly higher amounts in irradiated nucleoids of both Deinococcus species.
      We observed, by immunofluorescence microscopy, the subcellular localization of
      these proteins in D. radiodurans, showing for the first time the recruitment of
      the DdrD protein into the D. radiodurans nucleoid. We specifically followed the
      kinetics of recruitment of RecA, DdrA, and DdrD to the nucleoid after
      irradiation. Remarkably, RecA proteins formed irregular filament-like structures
      1 h after irradiation, before being redistributed throughout the cells by 3 h
      post-irradiation. Comparable dynamics of DdrD localization were observed,
      suggesting a possible functional interaction between RecA and DdrD. Several
      proteins involved in nucleotide synthesis were also seen in higher quantities in
      the nucleoids of irradiated cells, indicative of the existence of a mechanism for
      orchestrating the presence of proteins involved in DNA metabolism in nucleoids in
      response to massive DNA damage. All MS data have been deposited in the
      ProteomeXchange with identifier PXD00196
      (http://proteomecentral.proteomexchange.org/dataset/PXD000196). 

PMID- 24307637
TI  - Antioxidant supplementation enhances bacterial peritonitis in mice by inhibiting
      phagocytosis.
AB  - Antioxidants are known to exhibit numerous health benefits including anti-ageing,
      anti-apoptotic and immuno-stimulatory effects. However, we present the data
      showing counterproductive effects of therapeutically relevant antioxidants on
      bacterial clearance by the immune system in a murine peritonitic model. The
      antioxidants ascorbic acid, glutathione and N-acetylcysteine augmented morbidity
      and mortality in mice carrying Eshcerichia coli-induced acute bacterial
      peritonitis. Treatment of peritonitic mice with antioxidants significantly
      increased their bacterial load in the range of 0.3-2 logs. Antioxidant
      administration to peritonitic mice resulted in decreased numbers of macrophages,
      B-cells and dendritic cells at the primary site of infection and increased
      neutrophil infiltration. Serum TNF-alpha levels were also decreased in
      antioxidant-treated peritonitic mice. In vitro experiments showed that
      antioxidants reduced the phagocytic efficacy of peritoneal macrophages by ~60-75%
      and also decreased E. coli-induced oxidative burst in macrophages cells. Taken
      together, our data indicate that the antioxidants increased the severity of
      peritonitis by decreasing the phagocytic efficiency, oxidative burst, and TNF
      alpha production, and increasing neutrophil infiltration. Based on these results,
      we propose that antioxidant supplementation during the course of bacterial
      infection is not recommended as it could be detrimental for the host. In
      addition, the present study underlines the importance of timing and context of
      antioxidant administration rather than indiscriminate usage to gain the best
      possible therapeutic advantage of these redox compounds.

PMID- 24307638
TI  - Direct Spectroscopic detection of the orientation of free OH groups in methyl
      lactate-(water)(1,2) clusters: hydration of a chiral hydroxy ester.
AB  - Hydration of chiral molecules is a subject of significant current interest in
      light of recent experimental observations of chirality transfer from chiral
      solutes to water in solution and the important roles which water plays in
      biological events. Using a broadband chirped pulse and a cavity based microwave
      spectrometer, we detected spectroscopic signatures of the mono- and dihydrates of
      methyl lactate, a chiral hydroxy ester. Surprisingly, these small hydration
      clusters show highly specific binding preferences. Not only do they strongly
      prefer the insertion H-bonding topology, but they also favor specific pointing
      direction(s) for their non-H-bonded hydroxy group(s). We observed that the
      particular dihydrate conformer identified is not the most stable one predicted.
      This work highlights the superior capability of high-resolution spectroscopy to
      identify specific water binding topologies, and provides quantitative data to
      test state-of-the-art theory. 

PMID- 24307639
TI  - MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of
      human stromal stem cells.
AB  - Osteoblast differentiation and bone formation (osteogenesis) are regulated by
      transcriptional and post-transcriptional mechanisms. Recently, microRNAs (miRNAs)
      were identified as novel key regulators of human stromal (skeletal, mesenchymal)
      stem cells (hMSC) differentiation. Here, we identified miRNA-34a (miR-34a) and
      its target protein networks as modulator of osteoblastic (OB) differentiation of
      hMSC. miRNA array profiling and further validation by quantitative RT-PCR
      revealed that miR-34a was upregulated during OB differentiation of hMSC, and in
      situ hybridization confirmed its OB expression in vivo. Overexpression of miR-34a
      inhibited early commitment and late OB differentiation of hMSC in vitro, whereas
      inhibition of miR-34a by anti-miR-34a enhanced these processes. Target prediction
      analysis and experimental validation confirmed Jagged1 (JAG1), a ligand for Notch
      1, as a bona fide target of miR-34a. siRNA-mediated reduction of JAG1 expression
      inhibited OB differentiation. Moreover, a number of known cell cycle regulator
      and cell proliferation proteins, such as cyclin D1, cyclin-dependent kinase 4 and
      6 (CDK4 and CDK6), E2F transcription factor three, and cell division cycle 25
      homolog A were among miR-34a targets. Furthermore, in a preclinical model of in
      vivo bone formation, overexpression of miR-34a in hMSC reduced heterotopic bone
      formation by 60%, and conversely, in vivo bone formation was increased by 200% in
      miR-34a-deficient hMSC. miRNA-34a exhibited unique dual regulatory effects
      controlling both hMSC proliferation and OB differentiation. Tissue-specific
      inhibition of miR-34a might be a potential novel therapeutic strategy for
      enhancing in vivo bone formation.

PMID- 24307640
TI  - CNS lymphoma in a patient with Shwachman Diamond syndrome.

PMID- 24307654
TI  - Modeling the contribution of toxicokinetic and toxicodynamic processes to the
      recovery of Gammarus pulex populations after exposure to pesticides.
AB  - Because aquatic macroinvertebrates may be exposed regularly to pesticides in edge
      of-the-field water bodies, an accurate assessment of potential adverse effects
      and subsequent population recovery is essential. Standard effect risk assessment
      tools are not able to fully address the complexities arising from multiple
      exposure patterns, nor can they properly address the population recovery process.
      In the present study, we developed an individual-based model of the freshwater
      amphipod Gammarus pulex to evaluate the consequences of exposure to 4 compounds
      with different modes of action on individual survival and population recovery.
      Effects on survival were calculated using concentration-effect relationships and
      the threshold damage model (TDM), which accounts for detailed processes of
      toxicokinetics and toxicodynamics. Delayed effects as calculated by the TDM had a
      significant impact on individual survival and population recovery. We also
      evaluated the standard assessment of effects after short-term exposures using the
      96-h concentration-effect model and the TDM, which was conservative for very
      short-term exposure. An integration of a TKTD submodel with a population model
      can be used to explore the ecological relevance of ecotoxicity endpoints in
      different exposure environments.

PMID- 24307641
TI  - 25th anniversary article: A soft future: from robots and sensor skin to energy
      harvesters.
AB  - Scientists are exploring elastic and soft forms of robots, electronic skin and
      energy harvesters, dreaming to mimic nature and to enable novel applications in
      wide fields, from consumer and mobile appliances to biomedical systems, sports
      and healthcare. All conceivable classes of materials with a wide range of
      mechanical, physical and chemical properties are employed, from liquids and gels
      to organic and inorganic solids. Functionalities never seen before are achieved.
      In this review we discuss soft robots which allow actuation with several degrees
      of freedom. We show that different actuation mechanisms lead to similar
      actuators, capable of complex and smooth movements in 3d space. We introduce
      latest research examples in sensor skin development and discuss ultraflexible
      electronic circuits, light emitting diodes and solar cells as examples.
      Additional functionalities of sensor skin, such as visual sensors inspired by
      animal eyes, camouflage, self-cleaning and healing and on-skin energy storage and
      generation are briefly reviewed. Finally, we discuss a paradigm change in energy
      harvesting, away from hard energy generators to soft ones based on dielectric
      elastomers. Such systems are shown to work with high energy of conversion, making
      them potentially interesting for harvesting mechanical energy from human gait,
      winds and ocean waves. 

PMID- 24307655
TI  - Utilization patterns of antihyperuricemic agents following safety announcement on
      allopurinol and benzbromarone by Taiwan Food and Drug Administration.
AB  - OBJECTIVE: The purpose of this study is to evaluate the utilization of four
      approved antihyperuricemic agents in Taiwan before and after two safety
      announcements rescinded an indication for allopurinol and added a warning on
      benzbromarone-induced hepatotoxicity in the year 2005. METHODS: An interrupted
      time series design and segmented regression models were used to examine impacts
      of the safety announcements on the utilization of allopurinol, benzbromarone,
      probenecid, or sulfinpyrazone. All outpatient prescriptions of the four
      antihyperuricemic agents were extracted from a longitudinal cohort dataset with
      1000000 individuals randomly sampled from the National Health Insurance Research
      Database. We examined utilization patterns of antihyperuricemic agents before and
      after the policy intervention (i.e., safety announcements and labeling changes of
      allopurinol and benzbromarone) in the year 2005. RESULTS: Following the safety
      announcements, there was a reduction in the number of allopurinol users in the
      first year of intervention (-95.82 users per 100000 persons, 95%CI, [-166.84, 
      24.80]) and a continuous reduction afterward at a rate of -53.17 per 100000
      persons per year. The utilization of benzbromarone grew steadily before 2005 but
      decreased drastically after the intervention, with a 30.12% reduction in the
      number of users by the end of year 2008. There was no commensurate change in the
      number of probenecid or sulfinpyrazone users after the intervention. CONCLUSIONS:
      Further research is required to evaluate the direct impacts of the safety
      announcements on clinical outcomes, treatment costs, and patient's quality of
      life.

PMID- 24307656
TI  - Cardioprotective effect of high-dose intragraft adenosine infusion on
      microvascular function and prevention of no-reflow during saphenous vein grafts
      intervention.
AB  - BACKGROUND: Despite the use of embolic protection devices, no-reflow can still
      occur during saphenous vein grafts (SVGs) intervention. High-dose intracoronary
      adenosine infusion preconditions the myocardium, improves coronary flow, and
      prevents no-reflow. The role of high-dose intragraft adenosine infusion on
      protection of microvascular function and prevention of no-reflow has not been
      investigated OBJECTIVES: We investigated the cardioprotective effect of high-dose
      intragraft adenosine infusion, compared with placebo, on microvascular function
      and prevention of no-reflow during SVGs intervention. METHODS: We randomized 22
      patients with SVGs stenoses to receive either a 10-min intragraft adenosine
      infusion (200 MUg/min; total dose = 2,000 MUg) or normal saline prior to
      stenting. Average peak velocity (APV), coronary flow velocity reserve (CVR),
      thrombolysis in myocardial infarction (TIMI) frame count (TFC), TIMI myocardial
      perfusion grade (TMPG), and the rate of no-reflow were compared between the two
      groups before adenosine or saline infusions and after stenting RESULTS: After
      stenting, hyperemic APV, CVR, and TMPG were significantly higher in the adenosine
      treated group than in the control group (60 +/- 18 vs. 35 +/- 10 cm/sec; 2.6 +/-
      0.54 vs. 1.8 +/- 0.47; and 2.8 +/- 0.90 vs. 2.1 +/- 0.80, respectively; P < 0.05.
      TFC was significantly lower in the adenosine-treated group than in the control
      group (14 +/- 3.0 vs. 26 +/- 13; P < 0.05). In the control group, four patients
      (36%) developed no-reflow compared to none in the adenosine-treated patient; P <
      0.05 CONCLUSIONS: This study provides the first evidence that high-dose
      intragraft adenosine infusion compared with placebo protects microvascular
      function and prevents no-reflow during SVGs intervention.

PMID- 24307657
TI  - Inhibition of constitutively active Stat3 reverses enzalutamide resistance in
      LNCaP derivative prostate cancer cells.
AB  - PURPOSE: Use of enzalutamide has improved the treatment of advanced prostate
      cancer. However, resistance to enzalutamide can develop frequently in initial
      responders. This study aimed to test whether overexpression of IL-6 and
      constitutive activation of Stat3 in prostate cancer cells increase resistance to
      enzalutamide. EXPERIMENTAL DESIGN: Sensitivity of prostate cancer cells to
      enzalutamide was tested using cell growth assays and clonogenic assays.
      Quantitative reverse transcription-PCR, ELISA, and Western blotting were
      performed to detect expression levels of IL-6, c-Myc, survivin, and AR.
      Expression of Stat3 was downregulated using siRNA specific to Stat3. ChIP assay
      was performed to examine recruitment of AR to the PSA promoter. RESULTS: Prostate
      cancer cells expressing autocrine IL-6 are resistant to enzalutamide and
      autocrine IL-6 leads to constitutive activation of Stat3 and its target genes.
      Down regulation of Stat3 led to an increase in sensitivity of prostate cancer
      cells to enzalutamide. Overexpression of constitutively active Stat3 in prostate
      cancer cells induced resistance to enzalutamide treatment. Constitutively active
      Stat3 also enhanced the recruitment of AR to PSA promoter which could not be
      disrupted by enzalutamide. The Stat3 inhibitor AG490 reversed enzalutamide
      resistance in prostate cancer cells, while combination treatment with
      enzalutamide and AG490 significantly inhibited cell growth and induced cell
      apoptosis. CONCLUSIONS: This study demonstrates that the autocrine IL-6 pathway
      induces enzalutamide resistance in prostate cancer cells via the constitutive
      activation of Stat3. Co-targeting IL6-Stat3 pathway with enzalutamide may be
      utilized for treatment of advanced prostate cancer.

PMID- 24307658
TI  - Salinity affects microbial activity and soil organic matter content in tidal
      wetlands.
AB  - Climate change-associated sea level rise is expected to cause saltwater intrusion
      into many historically freshwater ecosystems. Of particular concern are tidal
      freshwater wetlands, which perform several important ecological functions
      including carbon sequestration. To predict the impact of saltwater intrusion in
      these environments, we must first gain a better understanding of how salinity
      regulates decomposition in natural systems. This study sampled eight tidal
      wetlands ranging from freshwater to oligohaline (0-2 ppt) in four rivers near the
      Chesapeake Bay (Virginia). To help isolate salinity effects, sites were selected
      to be highly similar in terms of plant community composition and tidal influence.
      Overall, salinity was found to be strongly negatively correlated with soil
      organic matter content (OM%) and C : N, but unrelated to the other studied
      environmental parameters (pH, redox, and above- and below-ground plant biomass).
      Partial correlation analysis, controlling for these environmental covariates,
      supported direct effects of salinity on the activity of carbon-degrading
      extracellular enzymes (beta-1, 4-glucosidase, 1, 4-beta-cellobiosidase, beta-D
      xylosidase, and phenol oxidase) as well as alkaline phosphatase, using a per unit
      OM basis. As enzyme activity is the putative rate-limiting step in decomposition,
      enhanced activity due to salinity increases could dramatically affect soil OM
      accumulation. Salinity was also found to be positively related to bacterial
      abundance (qPCR of the 16S rRNA gene) and tightly linked with community
      composition (T-RFLP). Furthermore, strong relationships were found between
      bacterial abundance and/or composition with the activity of specific enzymes (1,
      4-beta-cellobiosidase, arylsulfatase, alkaline phosphatase, and phenol oxidase)
      suggesting salinity's impact on decomposition could be due, at least in part, to
      its effect on the bacterial community. Together, these results indicate that
      salinity increases microbial decomposition rates in low salinity wetlands, and
      suggests that these ecosystems may experience decreased soil OM accumulation,
      accretion, and carbon sequestration rates even with modest levels of saltwater
      intrusion. 

PMID- 24307659
TI  - Stereoselective nucleophilic fluoromethylation of aryl ketones: dynamic kinetic
      resolution of chiral alpha-fluoro carbanions.
AB  - Although many methods are available for the synthesis of optically enriched
      monofluoromethyl secondary alcohols, synthesizing optically enriched
      monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to
      handle nucleophilic fluoromethylation protocol was developed. The current
      monofluoromethylation showed much higher facial selectivity than the
      corresponding difluoromethylation and proceeded via a different type of
      transition state. Excellent stereoselective control at the fluorinated carbon
      chiral center was found, an effect believed to be facilitated by the dynamic
      kinetic resolution of the chiral alpha-fluoro carbanions. 

PMID- 24307660
TI  - Successful treatment of severe myasthenia gravis developed after allogeneic
      hematopoietic stem cell transplantation with plasma exchange and rituximab.
AB  - Myasthenia gravis is among the rare complications after allogeneic hematopoietic
      stem cell transplantation and is usually associated with chronic GVHD. Herein, we
      report a 2-year and 10 months of age female with Griscelli syndrome, who
      developed severe myasthenia gravis at post-transplant +22nd month and required
      respiratory support with mechanical ventilation. She was unresponsive to
      cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate
      mofetil and the symptoms could only be controlled after plasma exchange and
      subsequent use of rituximab, in addition to cyclosporine A and mycophenolate
      mofetil maintenance. She is currently asymptomatic on the 6th month of follow-up.

PMID- 24307661
TI  - Understanding control of calcitic biomineralization-proteomics to the rescue.
AB  - The avian eggshell is one of the fastest calcifying processes known and
      represents a unique model for studying biomineralization. Eggshell strength is a
      crucial economic trait for table egg production, and ensures that a safe egg
      reaches the consumer kitchen. However, a common toolkit for eggshell
      mineralization has not yet been defined. In this issue, label-free MS-based
      protein quantification technology has been used by Sun et al. (Proteomics 2013,
      13, 3523-3536) to detect differences in protein abundance between eggshell matrix
      from strong and weak eggs and between the corresponding uterine fluids bathing
      strong and weak eggs. Proteins associated with the formation of strong eggshells
      are identified, which are now candidates for further investigations to define the
      regulatory relationship between specific eggshell matrix proteins and calcite
      crystal texture. 

PMID- 24307662
TI  - Implications of climate change for potamodromous fishes.
AB  - There is little understanding of how climate change will impact potamodromous
      freshwater fishes. Since the mid 1970s, a decline in annual rainfall in south
      western Australia (a globally recognized biodiversity hotspot) has resulted in
      the rivers of the region undergoing severe reductions in surface flows (ca. 50%).
      There is universal agreement amongst Global Climate Models that rainfall will
      continue to decline in this region. Limited data are available on the movement
      patterns of the endemic freshwater fishes of south-western Australia or on the
      relationship between their life histories and hydrology. We used this region as a
      model to determine how dramatic hydrological change may impact potamodromous
      freshwater fishes. Migration patterns of fishes in the largest river in south
      western Australia were quantified over a 4 year period and were related to a
      number of key environmental variables including discharge, temperature, pH,
      conductivity and dissolved oxygen. Most of the endemic freshwater fishes were
      potamodromous, displaying lateral seasonal spawning migrations from the main
      channel into tributaries, and there were significant temporal differences in
      movement patterns between species. Using a model averaging approach, amount of
      discharge was clearly the best predictor of upstream and downstream movement for
      most species. Given past and projected reductions in surface flow and
      groundwater, the findings have major implications for future recruitment rates
      and population viabilities of potamodromous fishes. Freshwater ecosystems in
      drying climatic regions can only be managed effectively if such hydro-ecological
      relationships are considered. Proactive management and addressing existing
      anthropogenic stressors on aquatic ecosystems associated with the development of
      surface and groundwater resources and land use is required to increase the
      resistance and resilience of potamodromous fishes to ongoing flow reductions. 

PMID- 24307663
TI  - Magnetic bead assisted labeling of antibodies at nanogram scale.
AB  - There are currently several initiatives that aim to produce binding reagents for
      proteome-wide analysis. To enable protein detection, visualization, and target
      quantification, covalent coupling of reporter molecules to antibodies is
      essential. However, current labeling protocols recommend considerable amount of
      antibodies, require antibody purity and are not designed for automation. Given
      that small amounts of antibodies are often sufficient for downstream analysis, we
      developed a labeling protocol that combines purification and modification of
      antibodies at submicrogram quantities. With the support of magnetic microspheres,
      automated labeling of antibodies in parallel using biotin or fluorescent dyes was
      achieved. 

PMID- 24307664
TI  - Commitment to cyst formation in Giardia.
AB  - Giardia trophozoites differentiate into infectious cysts (encystment) in response
      to physiological stimuli; encystment is crucial for Giardia's transmission,
      survival and pathogenesis. In vitro, Giardia encysts when bile sequesters lipids
      necessary for this lipid auxotroph, and in vivo they encyst to infect new hosts.
      In this study, we investigated, for the first time, commitment to encystment in
      Giardia using both molecular and cellular techniques. We show that after 3-6 h in
      inducing conditions, encysting trophozoites continue to encyst regardless of
      whether the inducing stimulus remains. We propose that a trophozoite's inability
      to revert to a growing or dividing trophozoite represents a commitment to
      encystment. The onset of commitment correlated with the appearance of encystment
      specific vesicles (ESVs) and encystment specific protein synthesis. These
      observations suggest the involvement of regulatory pathways with the ability to
      'remember' a transient signal long after its removal; a property that enables
      encysting trophozoites to complete the encystment process should the unfavourable
      triggering condition(s) change. The ability to form cysts in response to
      transient signals or, as we have highlighted in this paper, the ability of a
      small percentage of the population to form cysts without an inducer is vital for
      the maintenance of infection within populations. 

PMID- 24307665
TI  - Adaptive response of Amphibacillus xylanus to normal aerobic and forced oxidative
      stress conditions.
AB  - Amphibacillus xylanus grows at the same rate and with the same cell yield under
      aerobic and anaerobic conditions. Under aerobic conditions, it exhibits vigorous
      oxygen consumption in spite of lacking a respiratory system and haem catalase. To
      understand the adaptive response of A. xylanus to oxidative stresses, a genomic
      analysis of A. xylanus was conducted. The analysis showed that A. xylanus has the
      genes of four metabolic systems: two pyruvate metabolic pathways, a glycolytic
      metabolic pathway and an NADH oxidase (Nox)-AhpC (Prx) system. A transcriptional
      study confirmed that A. xylanus has these metabolic systems. Moreover, genomic
      analysis revealed the presence of two genes for NADH oxidase (nox1 and nox2),
      both of which were identified in the transcriptional analysis. The nox1 gene in
      A. xylanus was highly expressed under normal aerobic conditions but that of nox2
      was not. A purification study of NADH oxidases indicated that the gene product of
      nox1 is a primary metabolic enzyme responsible for metabolism of both oxygen and
      reactive oxygen species. A. xylanus was successfully grown under forced oxidative
      stress conditions such as 0.1 mM H2O2, 0.3 mM paraquat and 80 % oxygen. Proteomic
      analysis revealed that manganese SOD, Prx, pyruvate dehydrogenase complex E1 and
      E3 components, and riboflavin synthase beta-chain are induced under normal
      aerobic conditions, and the other proteins except the five aerobically induced
      proteins were not induced under forced oxidative stress conditions. Taken
      together, the present findings indicate that A. xylanus has a unique defence
      system against forced oxidative stress. 

PMID- 24307666
TI  - The FupA/B protein uniquely facilitates transport of ferrous iron and siderophore
      associated ferric iron across the outer membrane of Francisella tularensis live
      vaccine strain.
AB  - Francisella tularensis is a highly infectious Gram-negative pathogen that
      replicates intracellularly within the mammalian host. One of the factors
      associated with virulence of F. tularensis is the protein FupA that mediates high
      affinity transport of ferrous iron across the outer membrane. Together with its
      paralogue FslE, a siderophore-ferric iron transporter, FupA supports survival of
      the pathogen in the host by providing access to the essential nutrient iron. The
      FupA orthologue in the attenuated live vaccine strain (LVS) is encoded by the
      hybrid gene fupA/B, the product of an intergenic recombination event that
      significantly contributes to attenuation of the strain. We used (55)Fe transport
      assays with mutant strains complemented with the different paralogues to show
      that the FupA/B protein of LVS retains the capacity for high-affinity transport
      of ferrous iron, albeit less efficiently than FupA of virulent strain Schu S4.
      (55)Fe transport assays using purified siderophore and siderophore-dependent
      growth assays on iron-limiting agar confirmed previous findings that FupA/B also
      contributes to siderophore-mediated ferric iron uptake. These assays further
      demonstrated that the LVS FslE protein is a weaker siderophore-ferric iron
      transporter than the orthologue from Schu S4, and may be a result of the sequence
      variation between the two proteins. Our results indicate that iron-uptake
      mechanisms in LVS differ from those in Schu S4 and that functional differences in
      the outer membrane iron transporters have distinct effects on growth under iron
      limitation. 

PMID- 24307667
TI  - Interaction complexity matters: disentangling services and disservices of ant
      communities driving yield in tropical agroecosystems.
AB  - Owing to complex direct and indirect effects, impacts of higher trophic levels on
      plants is poorly understood. In tropical agroecosystems, ants interact with crop
      mutualists and antagonists, but little is known about how this integrates into
      the final ecosystem service, crop yield. We combined ant exclusion and
      introduction of invasive and native-dominant species in cacao agroecosystems to
      test whether (i) ant exclusion reduces yield, (ii) dominant species maximize
      certain intermediate ecosystem services (e.g. control of specific pests) rather
      than yield, which depends on several, cascading intermediate services and (iii)
      even, species-rich ant communities result in highest yields. Ants provided
      services, including reduced leaf herbivory and fruit pest damage and indirect
      pollination facilitation, but also disservices, such as increased mealybug
      density, phytopathogen dissemination and indirect pest damage enhancement. Yields
      were highest with unmanipulated, species-rich, even communities, whereas ant
      exclusion decreased yield by 27%. Introduction of an invasive-dominant ant
      decreased species density and evenness and resulted in 34% lower yields, whereas
      introduction of a non-invasive-dominant species resulted in similar species
      density and yields as in the unmanipulated control. Species traits and ant
      community structure affect services and disservices for agriculture in
      surprisingly complex ways, with species-rich and even communities promoting
      highest yield. 

PMID- 24307668
TI  - Drivers of protogynous sex change differ across spatial scales.
AB  - The influence of social demography on sex change schedules in protogynous reef
      fishes is well established, yet effects across spatial scales (in particular, the
      magnitude of natural variation relative to size-selective fishing effects) are
      poorly understood. Here, I examine variation in timing of sex change for
      exploited parrotfishes across a range of environmental, anthropogenic and
      geographical factors. Results were highly dependent on spatial scale. Fishing
      pressure was the most influential factor determining length at sex change at the
      within-island scale where a wide range of anthropogenic pressure existed. Sex
      transition occurred at smaller sizes where fishing pressure was high. Among
      islands, however, differences were overwhelmingly predicted by reefal-scale
      structural features, a pattern evident for all species examined. For the most
      abundant species, Chlorurus spilurus, length at sex change increased at higher
      overall densities and greater female-to-male sex ratios at all islands except
      where targeted by fishermen; here the trend was reversed. This implies differing
      selective pressures on adult individuals can significantly alter sex change
      dynamics, highlighting the importance of social structure, demography and the
      selective forces structuring populations. Considerable life-history responses to
      exploitation were observed, but results suggest potential fishing effects on
      demography may be obscured by natural variation at biogeographic scales. 

PMID- 24307669
TI  - Bee pollination improves crop quality, shelf life and commercial value.
AB  - Pollination improves the yield of most crop species and contributes to one-third
      of global crop production, but comprehensive benefits including crop quality are
      still unknown. Hence, pollination is underestimated by international policies,
      which is particularly alarming in times of agricultural intensification and
      diminishing pollination services. In this study, exclusion experiments with
      strawberries showed bee pollination to improve fruit quality, quantity and market
      value compared with wind and self-pollination. Bee-pollinated fruits were
      heavier, had less malformations and reached higher commercial grades. They had
      increased redness and reduced sugar-acid-ratios and were firmer, thus improving
      the commercially important shelf life. Longer shelf life reduced fruit loss by at
      least 11%. This is accounting for 0.32 billion US$ of the 1.44 billion US$
      provided by bee pollination to the total value of 2.90 billion US$ made with
      strawberry selling in the European Union 2009. The fruit quality and yield
      effects are driven by the pollination-mediated production of hormonal growth
      regulators, which occur in several pollination-dependent crops. Thus, our
      comprehensive findings should be transferable to a wide range of crops and
      demonstrate bee pollination to be a hitherto underestimated but vital and
      economically important determinant of fruit quality. 

PMID- 24307670
TI  - Ecological effects of ocean acidification and habitat complexity on reef
      associated macroinvertebrate communities.
AB  - The ecological effects of ocean acidification (OA) from rising atmospheric carbon
      dioxide (CO2) on benthic marine communities are largely unknown. We investigated
      in situ the consequences of long-term exposure to high CO2 on coral-reef
      associated macroinvertebrate communities around three shallow volcanic CO2 seeps
      in Papua New Guinea. The densities of many groups and the number of taxa (classes
      and phyla) of macroinvertebrates were significantly reduced at elevated CO2 (425
      1100 uatm) compared with control sites. However, sensitivities of some groups,
      including decapod crustaceans, ascidians and several echinoderms, contrasted with
      predictions of their physiological CO2 tolerances derived from laboratory
      experiments. High CO2 reduced the availability of structurally complex corals
      that are essential refugia for many reef-associated macroinvertebrates. This loss
      of habitat complexity was also associated with losses in many macroinvertebrate
      groups, especially predation-prone mobile taxa, including crustaceans and
      crinoids. The transition from living to dead coral as substratum and habitat
      further altered macroinvertebrate communities, with far more taxa losing than
      gaining in numbers. Our study shows that indirect ecological effects of OA
      (reduced habitat complexity) will complement its direct physiological effects and
      together with the loss of coral cover through climate change will severely affect
      macroinvertebrate communities in coral reefs. 

PMID- 24307671
TI  - Individual differences affect honest signalling in a songbird.
AB  - Research in the past decade has established the existence of consistent
      individual differences or 'personality' in animals and their important role in
      many aspects of animal behaviour. At the same time, research on honest signalling
      of aggression has revealed that while some of the putative aggression signals are
      reliable, they are only imperfectly so. This study asks whether a significant
      portion of the variance in the aggression-signal regression may be explained by
      individual differences in signalling strategies. Using the well-studied
      aggressive signalling system of song sparrows (Melospiza melodia), we carried out
      repeated assays to measure both aggressive behaviours and aggressive signalling
      of territorial males. Through these assays, we found that aggressive behaviours
      and aggressive signalling were both highly repeatable, and moreover that
      aggressive behaviours in 2009-2010 predicted whether the birds would attack a
      taxidermic mount over a year later. Most significantly, we found that residual
      variation in signalling behaviours, after controlling for aggressive behaviour,
      was individually consistent, suggesting there may be a second personality trait
      determining the level of aggressive signalling. We term this potential
      personality trait 'communicativeness' and discuss these results in the context of
      honest signalling theories and recent findings reporting prevalence of 'under
      signalling'. 

PMID- 24307672
TI  - Mating systems and protein-protein interactions determine evolutionary rates of
      primate sperm proteins.
AB  - To assess the relative impact of functional constraint and post-mating sexual
      selection on sequence evolution of reproductive proteins, we examined 169 primate
      sperm proteins. In order to recognize potential genome-wide trends, we
      additionally analysed a sample of altogether 318 non-reproductive (brain and
      postsynaptic) proteins. Based on cDNAs of eight primate species (Anthropoidea),
      we observed that pre-mating sperm proteins engaged in sperm composition and
      assembly show significantly lower incidence of site-specific positive selection
      and overall lower non-synonymous to synonymous substitution rates (dN/dS) across
      sites as compared with post-mating sperm proteins involved in capacitation,
      hyperactivation, acrosome reaction and fertilization. Moreover, database
      screening revealed overall more intracellular protein interaction partners in pre
      mating than in post-mating sperm proteins. Finally, post-mating sperm proteins
      evolved at significantly higher evolutionary rates than pre-mating sperm and non
      reproductive proteins on the branches to multi-male breeding species, while no
      such increase was observed on the branches to unimale and monogamous species. We
      conclude that less protein-protein interactions of post-mating sperm proteins
      account for lowered functional constraint, allowing for stronger impact of post
      mating sexual selection, while the opposite holds true for pre-mating sperm
      proteins. This pattern is particularly strong in multi-male breeding species
      showing high female promiscuity. 

PMID- 24307673
TI  - Fish introductions reveal the temperature dependence of species interactions.
AB  - A major area of current research is to understand how climate change will impact
      species interactions and ultimately biodiversity. A variety of environmental
      conditions are rapidly changing owing to climate warming, and these conditions
      often affect both the strength and outcome of species interactions. We used fish
      distributions and replicated fish introductions to investigate environmental
      conditions influencing the coexistence of two fishes in Swedish lakes: brown
      trout (Salmo trutta) and pike (Esox lucius). A logistic regression model of brown
      trout and pike coexistence showed that these species coexist in large lakes (more
      than 4.5 km(2)), but not in small, warm lakes (annual air temperature more than
      0.9-1.5 degrees C). We then explored how climate change will alter coexistence by
      substituting climate scenarios for 2091-2100 into our model. The model predicts
      that brown trout will be extirpated from approximately half of the lakes where
      they presently coexist with pike and from nearly all 9100 lakes where pike are
      predicted to invade. Context dependency was critical for understanding pike-brown
      trout interactions, and, given the widespread occurrence of context-dependent
      species interactions, this aspect will probably be critical for accurately
      predicting climate impacts on biodiversity. 

PMID- 24307674
TI  - Evidence of photosymbiosis in Palaeozoic tabulate corals.
AB  - Coral reefs form the most diverse of all marine ecosystems on the Earth. Corals
      are among their main components and owe their bioconstructing abilities to a
      symbiosis with algae (Symbiodinium). The coral-algae symbiosis had been traced
      back to the Triassic (ca 240 Ma). Modern reef-building corals (Scleractinia)
      appeared after the Permian-Triassic crisis; in the Palaeozoic, some of the main
      reef constructors were extinct tabulate corals. The calcium carbonate secreted by
      extant photosymbiotic corals bears characteristic isotope (C and O) signatures.
      The analysis of tabulate corals belonging to four orders (Favositida,
      Heliolitida, Syringoporida and Auloporida) from Silurian to Permian strata of
      Europe and Africa shows these characteristic carbon and oxygen stable isotope
      signatures. The delta(18)O to delta(13)C ratios in recent photosymbiotic
      scleractinians are very similar to those of Palaeozoic tabulates, thus providing
      strong evidence of such symbioses as early as the Middle Silurian (ca 430 Ma).
      Corals in Palaeozoic reefs used the same cellular mechanisms for carbonate
      secretion as recent reefs, and thus contributed to reef formation. 

PMID- 24307675
TI  - Recurrent gene loss correlates with the evolution of stomach phenotypes in
      gnathostome history.
AB  - The stomach, a hallmark of gnathostome evolution, represents a unique anatomical
      innovation characterized by the presence of acid- and pepsin-secreting glands.
      However, the occurrence of these glands in gnathostome species is not universal;
      in the nineteenth century the French zoologist Cuvier first noted that some
      teleosts lacked a stomach. Strikingly, Holocephali (chimaeras), dipnoids
      (lungfish) and monotremes (egg-laying mammals) also lack acid secretion and a
      gastric cellular phenotype. Here, we test the hypothesis that loss of the gastric
      phenotype is correlated with the loss of key gastric genes. We investigated
      species from all the main gnathostome lineages and show the specific contribution
      of gene loss to the widespread distribution of the agastric condition. We
      establish that the stomach loss correlates with the persistent and complete
      absence of the gastric function gene kit--H(+)/K(+)-ATPase (Atp4A and Atp4B) and
      pepsinogens (Pga, Pgc, Cym)--in the analysed species. We also find that in
      gastric species the pepsinogen gene complement varies significantly (e.g. two to
      four in teleosts and tens in some mammals) with multiple events of
      pseudogenization identified in various lineages. We propose that relaxation of
      purifying selection in pepsinogen genes and possibly proton pump genes in
      response to dietary changes led to the numerous independent events of stomach
      loss in gnathostome history. Significantly, the absence of the gastric genes
      predicts that reinvention of the stomach in agastric lineages would be highly
      improbable, in line with Dollo's principle.

PMID- 24307676
TI  - The consequences of balanced harvesting of fish communities.
AB  - Balanced harvesting, where species or individuals are exploited in accordance
      with their productivity, has been proposed as a way to minimize the effects of
      fishing on marine fish communities and ecosystems. This calls for a thorough
      examination of the consequences balanced harvesting has on fish community
      structure and yield. We use a size- and trait-based model that resolves
      individual interactions through competition and predation to compare balanced
      harvesting with traditional selective harvesting, which protects juvenile fish
      from fishing. Four different exploitation patterns, generated by combining
      selective or unselective harvesting with balanced or unbalanced fishing, are
      compared. We find that unselective balanced fishing, where individuals are
      exploited in proportion to their productivity, produces a slightly larger total
      maximum sustainable yield than the other exploitation patterns and, for a given
      yield, the least change in the relative biomass composition of the fish
      community. Because fishing reduces competition, predation and cannibalism within
      the community, the total maximum sustainable yield is achieved at high
      exploitation rates. The yield from unselective balanced fishing is dominated by
      small individuals, whereas selective fishing produces a much higher proportion of
      large individuals in the yield. Although unselective balanced fishing is
      predicted to produce the highest total maximum sustainable yield and the lowest
      impact on trophic structure, it is effectively a fishery predominantly targeting
      small forage fish. 

PMID- 24307677
TI  - The dark side of self-focus: brain activity during self-focus in low and high
      brooders.
AB  - There are two distinct modes of self-focus: analytical self-focus is abstract,
      general and evaluative whereas experiential self-focus is concrete, specific and
      non-evaluative. Using functional magnetic resonance imaging (fMRI), we
      investigated the neural bases of these two modes of self-focus in relation with
      brooding, the maladaptive form of rumination. Forty-one French-speaking right
      handed healthy young adults (10 men, mean age +/- s.d.: 21.8 +/- 2.3 years)
      engaged in analytical and experiential self-focus triggered by verbal stimuli
      during fMRI. Brooding was measured with the 22-item Rumination Response Style
      scale. Individuals with lower brooding scores showed greater activation of the
      posterior cingulate cortex/precuneus during analytical than experiential self
      focus, whereas individuals with higher brooding scores did not. This is
      consistent with the hypothesis that brooding is associated with less control over
      the nature of the self-focus engaged. These findings may help to refine our
      understanding of how rumination promotes depression through maladaptive self
      focus. 

PMID- 24307679
TI  - ATP increases within the lumen of the endoplasmic reticulum upon intracellular
      Ca2+ release.
AB  - Multiple functions of the endoplasmic reticulum (ER) essentially depend on ATP
      within this organelle. However, little is known about ER ATP dynamics and the
      regulation of ER ATP import. Here we describe real-time recordings of ER ATP
      fluxes in single cells using an ER-targeted, genetically encoded ATP sensor. In
      vitro experiments prove that the ATP sensor is both Ca(2+) and redox insensitive,
      which makes it possible to monitor Ca(2+)-coupled ER ATP dynamics specifically.
      The approach uncovers a cell type-specific regulation of ER ATP homeostasis in
      different cell types. Moreover, we show that intracellular Ca(2+) release is
      coupled to an increase of ATP within the ER. The Ca(2+)-coupled ER ATP increase
      is independent of the mode of Ca(2+) mobilization and controlled by the rate of
      ATP biosynthesis. Furthermore, the energy stress sensor, AMP-activated protein
      kinase, is essential for the ATP increase that occurs in response to Ca(2+)
      depletion of the organelle. Our data highlight a novel Ca(2+)-controlled process
      that supplies the ER with additional energy upon cell stimulation. 

PMID- 24307680
TI  - Biphasic influence of Miz1 on neural crest development by regulating cell
      survival and apical adhesion complex formation in the developing neural tube.
AB  - Myc interacting zinc finger protein-1 (Miz1) is a transcription factor known to
      regulate cell cycle- and cell adhesion-related genes in cancer. Here we show that
      Miz1 also plays a critical role in neural crest development. In the chick, Miz1
      is expressed throughout the neural plate and closing neural tube. Its morpholino
      mediated knockdown affects neural crest precursor survival, leading to reduction
      of neural plate border and neural crest specifier genes Msx-1, Pax7, FoxD3, and
      Sox10. Of interest, Miz1 loss also causes marked reduction of adhesion molecules
      (N-cadherin, cadherin6B, and alpha1-catenin) with a concomitant increase of E
      cadherin in the neural folds, likely leading to delayed and decreased neural
      crest emigration. Conversely, Miz1 overexpression results in up-regulation of
      cadherin6B and FoxD3 expression in the neural folds/neural tube, leading to
      premature neural crest emigration and increased number of migratory crest cells.
      Although Miz1 loss effects cell survival and proliferation throughout the neural
      plate, the neural progenitor marker Sox2 was unaffected, suggesting a neural
      crest-selective effect. The results suggest that Miz1 is important not only for
      survival of neural crest precursors, but also for maintenance of integrity of the
      neural folds and tube, via correct formation of the apical adhesion complex
      therein. 

PMID- 24307681
TI  - Exo70E2 is essential for exocyst subunit recruitment and EXPO formation in both
      plants and animals.
AB  - In contrast to a single copy of Exo70 in yeast and mammals, the Arabidopsis
      genome contains 23 paralogues of Exo70 (AtExo70). Using AtExo70E2 and its GFP
      fusion as probes, we recently identified a novel double-membrane organelle termed
      exocyst-positive organelle (EXPO) that mediates an unconventional protein
      secretion in plant cells. Here we further demonstrate that AtExo70E2 is essential
      for exocyst subunit recruitment and for EXPO formation in both plants and
      animals. By performing transient expression in Arabidopsis protoplasts, we
      established that a number of exocyst subunits (especially the members of the Sec
      family) are unable to be recruited to EXPO in the absence of AtExo70E2. The
      paralogue AtExo70A1 is unable to substitute for AtExo70E2 in this regard.
      Fluorescence resonance energy transfer assay and bimolecular fluorescence
      complementation analyses confirm the interaction between AtExo70E2 and Sec6 and
      Sec10. AtExo70E2, but not its yeast counterpart, is also capable of inducing EXPO
      formation in an animal cell line (HEK293A cells). Electron microscopy confirms
      the presence of double-membraned, EXPO-like structures in HEK293A cells
      expressing AtExo70E2. Inversely, neither human nor yeast Exo70 homologues cause
      the formation of EXPO in Arabidopsis protoplasts. These results point to a
      specific and crucial role for AtExo70E2 in EXPO formation. 

PMID- 24307682
TI  - The RAVE complex is an isoform-specific V-ATPase assembly factor in yeast.
AB  - The regulator of ATPase of vacuoles and endosomes (RAVE) complex is implicated in
      vacuolar H(+)-translocating ATPase (V-ATPase) assembly and activity. In yeast,
      rav1 mutants exhibit a Vma(-) growth phenotype characteristic of loss of V-ATPase
      activity only at high temperature. Synthetic genetic analysis identified
      mutations that exhibit a full, temperature-independent Vma(-) growth defect when
      combined with the rav1 mutation. These include class E vps mutations, which
      compromise endosomal sorting. The synthetic Vma(-) growth defect could not be
      attributed to loss of vacuolar acidification in the double mutants, as there was
      no vacuolar acidification in the rav1 mutant. The yeast V-ATPase a subunit is
      present as two isoforms, Stv1p in Golgi and endosomes and Vph1p in vacuoles.
      Rav1p interacts directly with the N-terminal domain of Vph1p. STV1 overexpression
      suppressed the growth defects of both rav1 and rav1vph1, and allowed RAVE
      independent assembly of active Stv1p-containing V-ATPases in vacuoles. Mutations
      causing synthetic genetic defects in combination with rav1 perturbed the normal
      localization of Stv1-green fluorescent protein. We propose that RAVE is necessary
      for assembly of Vph1-containing V-ATPase complexes but not Stv1-containing
      complexes. Synthetic Vma(-) phenotypes arise from defects in Vph1p-containing
      complexes caused by rav1, combined with defects in Stv1p-containing V-ATPases
      caused by the second mutation. Thus RAVE is the first isoform-specific V-ATPase
      assembly factor. 

PMID- 24307684
TI  - Risk of subsequent attention deficit-hyperactivity disorder in children with
      febrile seizures.
AB  - OBJECTIVE: In this study, we obtained relevant data from a nationwide cohort
      database to investigate the risk of attention deficit-hyperactivity disorder
      (ADHD) in children with a history of febrile seizures (FS). METHODS: We
      identified 1081 children with FS as the case cohort, and the date of diagnosis
      was used as an index date. Four controls were matched randomly with each case
      based on age, sex, urbanisation level, parents' occupation, and index date. We
      applied Cox's proportional hazards regression to estimate the HR and CI of FS
      associated ADHD. RESULTS: After 11 years of follow-up, the incidence of ADHD for
      the FS and control cohorts is 7.83 and 4.72 per 1000 person-years, respectively.
      The FS cohort was 1.66 times more at risk of ADHD occurrence (95% CI 1.27 to
      2.18) than the control cohort. The risk of developing ADHD increased in
      conjunction with the frequency of FS-related visits. CONCLUSIONS: FS may increase
      the risk of subsequent ADHD occurrence in children. Children who visited
      physicians for FS more than twice had a significantly higher cumulative incidence
      of ADHD.

PMID- 24307683
TI  - Cohesion promotes nucleolar structure and function.
AB  - The cohesin complex contributes to ribosome function, although the molecular
      mechanisms involved are unclear. Compromised cohesin function is associated with
      a class of diseases known as cohesinopathies. One cohesinopathy, Roberts syndrome
      (RBS), occurs when a mutation reduces acetylation of the cohesin Smc3 subunit.
      Mutation of the cohesin acetyltransferase is associated with impaired rRNA
      production, ribosome biogenesis, and protein synthesis in yeast and human cells.
      Cohesin binding to the ribosomal DNA (rDNA) is evolutionarily conserved from
      bacteria to human cells. We report that the RBS mutation in yeast (eco1-W216G)
      exhibits a disorganized nucleolus and reduced looping at the rDNA. RNA polymerase
      I occupancy of the genes remains normal, suggesting that recruitment is not
      impaired. Impaired rRNA production in the RBS mutant coincides with slower rRNA
      cleavage. In addition to the RBS mutation, mutations in any subunit of the
      cohesin ring are associated with defects in ribosome biogenesis. Depletion or
      artificial destruction of cohesion in a single cell cycle is associated with loss
      of nucleolar integrity, demonstrating that the defects at the rDNA can be
      directly attributed to loss of cohesion. Our results strongly suggest that
      organization of the rDNA provided by cohesion is critical for formation and
      function of the nucleolus. 

PMID- 24307685
TI  - Transcription factor and microRNA co-regulatory loops: important regulatory
      motifs in biological processes and diseases.
AB  - Transcription factors (TFs) and microRNAs (miRNAs) can jointly regulate target
      gene expression in the forms of feed-forward loops (FFLs) or feedback loops
      (FBLs). These regulatory loops serve as important motifs in gene regulatory
      networks and play critical roles in multiple biological processes and different
      diseases. Major progress has been made in bioinformatics and experimental study
      for the TF and miRNA co-regulation in recent years. To further speed up its
      identification and functional study, it is indispensable to make a comprehensive
      review. In this article, we summarize the types of FFLs and FBLs and their
      identified methods. Then, we review the behaviors and functions for the
      experimentally identified loops according to biological processes and diseases.
      Future improvements and challenges are also discussed, which includes more
      powerful bioinformatics approaches and high-throughput technologies in TF and
      miRNA target prediction, and the integration of networks of multiple levels. 

PMID- 24307686
TI  - Tissue- and stage-dependent dosage compensation on the neo-X chromosome in
      Drosophila pseudoobscura.
AB  - Sex chromosome dosage compensation (DC) is widely accepted in various organisms.
      This concept is mostly supported by comparisons of gene expression between
      chromosomes and between sexes. However, genes on the X chromosome and autosomes
      are mostly not homologous, and the average gene expression level on these
      chromosomes may not be the same even under DC, which complicates comparisons
      between chromosomes. Many genes with sex-biased expression also make comparisons
      between sexes difficult. To overcome these issues, we investigated DC by
      comparing the expression of neo-X-linked genes in Drosophila pseudoobscura with
      those of their autosomal orthologs in other Drosophila species. The ratio of the
      former to the latter in males would be 1 under DC, whereas it becomes 0.5 without
      DC. We found that the ratio was ~0.85 for adult whole bodies, indicating that the
      DC is incomplete on the neo-X chromosome in adults as a whole. The ratio (~0.90)
      was also significantly less than 1 for adult bodies without gonads, whereas it
      was ~1.0 for adult heads. These results indicate that DC varies among tissues.
      Our sliding-window analysis of the ratio also revealed that the upregulation of
      neo-X-linked genes in males occurred chromosome wide in all tissues analyzed,
      indicating global upregulation mechanisms. However, we found that gene functions
      also affected the levels of DC. Furthermore, most of the genes recently moved to
      the X were already under DC at the larval stage but not at the adult stage. These
      results suggest that DC in Drosophila species operates in a tissue/stage
      dependent manner. 

PMID- 24307687
TI  - Earliest Holozoan expansion of phosphotyrosine signaling.
AB  - Phosphotyrosine (pTyr) signaling is involved in development and maintenance of
      metazoans' multicellular body through cell-to-cell communication. Tyrosine
      kinases (TKs), tyrosine phosphatases, and other proteins relaying the signal
      compose the cascade. Domain architectures of the pTyr signaling proteins are
      diverse in metazoans, reflecting their complex intercellular communication.
      Previous studies had shown that the metazoan-type TKs, as well as other pTyr
      signaling proteins, were already diversified in the common ancestor of metazoans,
      choanoflagellates, and filastereans (which are together included in the clade
      Holozoa) whereas they are absent in fungi and other nonholozoan lineages.
      However, the earliest-branching holozoans Ichthyosporea and Corallochytrea, as
      well as the two fungi-related amoebae Fonticula and Nuclearia, have not been
      studied. Here, we analyze the complete genome sequences of two ichthyosporeans
      and Fonticula, and RNAseq data of three additional ichthyosporeans, one
      corallochytrean, and Nuclearia. Both the ichthyosporean and corallochytrean
      genomes encode a large variety of receptor TKs (RTKs) and cytoplasmic TKs (CTKs),
      as well as other pTyr signaling components showing highly complex domain
      architectures. However, Nuclearia and Fonticula have no TK, and show much less
      diversity in other pTyr signaling components. The CTK repertoires of both
      Ichthyosporea and Corallochytrea are similar to those of Metazoa,
      Choanoflagellida, and Filasterea, but the RTK sets are totally different from
      each other. The complex pTyr signaling equipped with positive/negative feedback
      mechanism likely emerged already at an early stage of holozoan evolution, yet
      keeping a high evolutionary plasticity in extracellular signal reception until
      the co-option of the system for cell-to-cell communication in metazoans. 

PMID- 24307688
TI  - A new formulation of protein evolutionary models that account for structural
      constraints.
AB  - Despite the importance of a thermodynamically stable structure with a conserved
      fold for protein function, almost all evolutionary models neglect site-site
      correlations that arise from physical interactions between neighboring amino acid
      sites. This is mainly due to the difficulty in formulating a computationally
      tractable model since rate matrices can no longer be used. Here, we introduce a
      general framework, based on factor graphs, for constructing probabilistic models
      of protein evolution with site interdependence. Conveniently, efficient
      approximate inference algorithms, such as Belief Propagation, can be used to
      calculate likelihoods for these models. We fit an amino acid substitution model
      of this type that accounts for both solvent accessibility and site-site
      correlations. Comparisons of the new model with rate matrix models and
      alternative structure-dependent models demonstrate that it better fits the
      sequence data. We also examine evolution within a family of homohexameric enzymes
      and find that site-site correlations between most contacting subunits contribute
      to a higher likelihood. In addition, we show that the new substitution model has
      a similar mathematical form to the one introduced in Rodrigue et al. (Rodrigue N,
      Lartillot N, Bryant D, Philippe H. 2005. Site interdependence attributed to
      tertiary structure in amino acid sequence evolution. Gene 347:207-217), although
      with different parameter interpretations and values. We also perform a
      statistical analysis of the effects of amino acids at neighboring sites on
      substitution probabilities and find a significant perturbation of most
      probabilities, further supporting the significant role of site-site interactions
      in protein evolution and motivating the development of new evolutionary models
      similar to the one described here. Finally, we discuss possible extensions and
      applications of the new substitution model. 

PMID- 24307689
TI  - Protecting research and a case for optimism.

PMID- 24307691
TI  - Tumor-associated immune parameters for personalized patient care.
AB  - The implementation of a robust technology adapted to clinical practice for the
      evaluation of the tumor-immune infiltrate is required to exploit its prognostic
      and theranostic value (Robins et al., this issue). 

PMID- 24307692
TI  - Indolcarboxamide is a preclinical candidate for treating multidrug-resistant
      tuberculosis.
AB  - New chemotherapeutic compounds against multidrug-resistant Mycobacterium
      tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis
      (TB). We have identified and characterized the indolcarboxamides as a new class
      of antitubercular bactericidal agent. Genetic and lipid profiling studies
      identified the likely molecular target of indolcarboxamides as MmpL3, a
      transporter of trehalose monomycolate that is essential for mycobacterial cell
      wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent
      activity against both drug-sensitive and multidrug-resistant clinical isolates of
      Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in
      several species enabled further evaluation for efficacy and safety. NITD-304 and
      NITD-349 were efficacious in treating both acute and chronic Mtb infections in
      mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks
      in exploratory rat toxicology studies revealed a promising safety margin.
      Finally, neither compound inhibited the activity of major cytochrome P-450
      enzymes or the hERG (human ether-a-go-go related gene) channel. These results
      suggest that NITD-304 and NITD-349 should undergo further development as a
      potential treatment for multidrug-resistant TB. 

PMID- 24307693
TI  - Digital genomic quantification of tumor-infiltrating lymphocytes.
AB  - Infiltrating T lymphocytes are frequently found in malignant tumors and are
      suggestive of a host cancer immune response. Multiple independent studies have
      documented that the presence and quantity of tumor-infiltrating lymphocytes
      (TILs) are strongly correlated with increased survival. However, because of
      methodological factors, the exact effect of TILs on prognosis has remained
      enigmatic, and inclusion of TILs in standard prognostic panels has been limited.
      For example, some reports enumerate all CD3(+) cells, some count only cytotoxic
      CD8(+) T cells, and the criteria used to score tumors as TIL-positive or TIL
      negative are inconsistent among studies. To address this limitation, we introduce
      a robust digital DNA-based assay, termed QuanTILfy, to count TILs and assess T
      cell clonality in tissue samples, including tumors. We demonstrate the clonal
      specificity of this approach by the diagnosis of T cell acute lymphoblastic
      leukemia and the accurate, sensitive, and highly reproducible measurement of TILs
      in primary and metastatic ovarian cancer. Our experiments demonstrate an
      association between higher TIL counts and improved survival among women with
      ovarian cancer, and are consistent with previous observations that the immune
      response against ovarian cancer is a meaningful and independent prognostic
      factor. Surprisingly, the TIL repertoire is diverse for all tumors in the study
      with no notable oligoclonal expansions. Furthermore, because variability in the
      measurement and characterization of TILs has limited their clinical utility as
      biomarkers, these results highlight the significant translational potential of a
      robust, standardizable DNA-based assay to assess TILs in a variety of cancer
      types. 

PMID- 24307694
TI  - Microfluidic CD4+ and CD8+ T lymphocyte counters for point-of-care HIV
      diagnostics using whole blood.
AB  - Roughly 33 million people worldwide are infected with HIV; disease burden is
      highest in resource-limited settings. One important diagnostic in HIV disease
      management is the absolute count of lymphocytes expressing the CD4(+) and CD8(+)
      receptors. The current diagnostic instruments and procedures require expensive
      equipment and trained technicians. In response, we have developed microfluidic
      biochips that count CD4(+) and CD8(+) lymphocytes in whole blood samples, without
      the need for off-chip sample preparation. The device is based on differential
      electrical counting and relies on five on-chip modules that, in sequence,
      chemically lyses erythrocytes, quenches lysis to preserve leukocytes, enumerates
      cells electrically, depletes the target cells (CD4 or CD8) with antibodies, and
      enumerates the remaining cells electrically. We demonstrate application of this
      chip using blood from healthy and HIV-infected subjects. Erythrocyte lysis and
      quenching durations were optimized to create pure leukocyte populations in less
      than 1 min. Target cell depletion was accomplished through shear stress-based
      immunocapture, using antibody-coated microposts to increase the contact surface
      area and enhance depletion efficiency. With the differential electrical counting
      method, device-based CD4(+) and CD8(+) T cell counts closely matched control
      counts obtained from flow cytometry, over a dynamic range of 40 to 1000
      cells/MUl. By providing accurate cell counts in less than 20 min, from samples
      obtained from one drop of whole blood, this approach has the potential to be
      realized as a handheld, battery-powered instrument that would deliver simple HIV
      diagnostics to patients anywhere in the world, regardless of geography or
      socioeconomic status. 

PMID- 24307695
TI  - Minimal residual disease monitoring with high-throughput sequencing of T cell
      receptors in cutaneous T cell lymphoma.
AB  - Mycosis fungoides (MF) and the leukemic presentation Sezary syndrome (SS) are
      clonal T cell lymphomas arising from the skin and are considered noncurable with
      standard therapies. To develop a specific and sensitive monitoring tool, we
      tested the ability of high-throughput sequencing (HTS) of T cell receptors (TCRB)
      to monitor minimal residual disease (MRD) after allogeneic hematopoietic cell
      transplantation. Genomic DNA was extracted from peripheral blood mononuclear
      cells (PBMCs) or skin samples. The rearranged TCRbeta loci were amplified using
      Vbeta- and Jbeta-specific primers, followed by HTS, to generate up to 1,000,000
      reads spanning the CDR3 region of individual cells. Malignant clones were
      identified in diagnostic samples in all cases by a dominant CDR3 sequence. Before
      transplant, four patients had circulating Sezary cells by the routine flow
      cytometry, which was confirmed by TCRB HTS. Although the flow cytometry found no
      detectable Sezary cells, malignant clones were detected by TCRB HTS in all other
      six cases. Five patients achieved "molecular remission" in blood between +30 and
      +540 days after transplant. Four of these patients also achieved molecular
      clearance in skin after transplant. Experiments using blood samples spiked with
      purified Sezary cells demonstrated that TCRB HTS can detect Sezary cells at the
      level of 1 in 50,000 PBMCs, which is more sensitive than standard diagnostics. We
      have thus demonstrated the utility of TCRB HTS to assess MRD with increased
      sensitivity and specificity compared to other current methodologies, and to
      monitor response to therapy in this MF/SS patient population. 

PMID- 24307696
TI  - The impact of miRNA-based molecular diagnostics and treatment of NRF2-stabilized
      tumors.
AB  - NF-E2-related factor 2 (NRF2) is a master transcriptional regulator that
      integrates cellular stress responses and is negatively regulated by Kelch-like
      ECH-associated protein 1 (KEAP1) at the posttranslational level. In human
      cancers, aberrantly stabilized NRF2, either by mutation of NRF2 or KEAP1, plays a
      vital role in chemoresistance and tumor cell growth through the transcriptional
      activation of target genes, suggesting that targeted inhibition of NRF2 is a
      potential therapy for NRF2-stabilized tumors. MicroRNAs (miRNA) are endogenous
      small noncoding RNAs that can negatively regulate gene expression by interfering
      with the translation or stability of target transcripts. Moreover, tumor
      suppressor miRNAs have been suggested to be useful for cancer treatment. Here, a
      reporter-coupled miRNA library screen identified four miRNAs (miR-507, -634, 
      450a, and -129-5p) that negatively regulate the NRF2-mediated oncogenic pathway
      by directly targeting NRF2. Importantly, downregulation of these miRNAs, in
      addition to the somatic mutation of NRF2 or KEAP1, is associated with stabilized
      NRF2 and poor prognosis in esophageal squamous cell carcinoma (ESCC).
      Furthermore, administration of a miR-507 alone or in combination with cisplatin
      inhibited tumor growth in vivo. Thus, these findings reveal that miRNA-based
      therapy is effective against NRF2-stabilized ESCC tumors. IMPLICATIONS: This
      study determines the potential of miRNA-based molecular diagnostics and
      therapeutics in NRF2-stablized tumors.

PMID- 24307697
TI  - Local transplantation of granulocyte colony stimulating factor-mobilized CD34+
      cells for patients with femoral and tibial nonunion: pilot clinical trial.
AB  - Most bone fractures typically heal, although a significant proportion (5%-10%) of
      fractures fail to heal, resulting in delayed union or persistent nonunion. Some
      preclinical evidence shows the therapeutic potential of peripheral blood CD34(+)
      cells, a hematopoietic/endothelial progenitor cell-enriched population, for bone
      fracture healing; however, clinical outcome following transplantation of CD34(+)
      cells in patients with fracture has never been reported. We report a phase I/IIa
      clinical trial regarding transplantation of autologous, granulocyte colony
      stimulating factor-mobilized CD34(+) cells with atelocollagen scaffold for
      patients with femoral or tibial fracture nonunion (n = 7). The primary endpoint
      of this study is radiological fracture healing (union) by evaluating
      anteroposterior and lateral views at week 12 following cell therapy. For the
      safety evaluation, incidence, severity, and outcome of all adverse events were
      recorded. Radiological fracture healing at week 12 was achieved in five of seven
      cases (71.4%), which was greater than the threshold (18.1%) predefined by the
      historical outcome of the standard of care. The interval between cell
      transplantation and union, the secondary endpoint, was 12.6 +/- 5.4 weeks (range,
      8-24 weeks) for clinical healing and 16.1 +/- 10.2 weeks (range, 8-36 weeks) for
      radiological healing. Neither deaths nor life-threatening adverse events were
      observed during the 1-year follow-up after the cell therapy. These results
      suggest feasibility, safety, and potential effectiveness of CD34(+) cell therapy
      in patients with nonunion. 

PMID- 24307698
TI  - Sox2 suppression by miR-21 governs human mesenchymal stem cell properties.
AB  - MicroRNAs (miRNAs) have recently been shown to act as regulatory signals for
      maintaining stemness and for determining the fate of adult and fetal stem cells,
      such as human mesenchymal stem cells (hMSCs). hMSCs constitute a population of
      multipotent stem cells that can be expanded easily in culture and are able to
      differentiate into many lineages. We have isolated two subpopulations of fetal
      mesenchymal stem cells (MSCs) from amniotic fluid (AF) known as spindle-shaped
      (SS) and round-shaped (RS) cells and characterized them on the basis of their
      phenotypes, pluripotency, proliferation rates, and differentiation potentials. In
      this study, we analyzed the miRNA profile of MSCs derived from AF, bone marrow
      (BM), and umbilical cord blood (UCB). We initially identified 67 different miRNAs
      that were expressed in all three types of MSCs but at different levels, depending
      on the source. A more detailed analysis revealed that miR-21 was expressed at
      higher levels in RS-AF-MSCs and BM-MSCs compared with SS-AF-MSCs. We further
      demonstrated for the first time a direct interaction between miR-21 and the
      pluripotency marker Sox2. The induction of miR-21 strongly inhibited Sox2
      expression in SS-AF-MSCs, resulting in reduced clonogenic and proliferative
      potential and cell cycle arrest. Strikingly, the opposite effect was observed
      upon miR-21 inhibition in RS-AF-MSCs and BM-MSCs, which led to an enhanced
      proliferation rate. Finally, miR-21 induction accelerated osteogenesis and
      impaired adipogenesis and chondrogenesis in SS-AF-MSCs. Therefore, these findings
      suggest that miR-21 might specifically function by regulating Sox2 expression in
      human MSCs and might also act as a key molecule determining MSC proliferation and
      differentiation. 

PMID- 24307699
TI  - Interactions between the regulatory subunit of type I protein kinase A and p90
      ribosomal S6 kinase1 regulate cardiomyocyte apoptosis.
AB  - Cardiomyocyte apoptosis contributes toward the loss of muscle mass in myocardial
      pathologies. Previous reports have implicated type I cAMP-dependent protein
      kinase (PKA) and p90 ribosomal S6 kinase (RSK) in cardiomyocyte apoptosis.
      However, the precise mechanisms and the isoform of RSK involved in this process
      remain undefined. Using adult rat ventricular myocytes and mouse-derived cardiac
      HL-1 cardiomyocytes, we demonstrate that hypoxia/reoxygenation (H/R)-induced
      apoptosis is accompanied by a decrease in the type I PKA regulatory subunit
      (PKARIalpha) and activation of RSK1. As previously described by us for other cell
      types, in cardiomyocytes, inactive RSK1 also interacts with PKARIalpha, whereas
      the active RSK1 interacts with the catalytic subunit of PKA. Additionally, small
      interfering (siRNA)-mediated silencing of PKARIalpha or disrupting the
      RSK1/PKARIalpha interactions with a small, cell-permeable peptide activates RSK1
      and recapitulates the H/R-induced apoptosis. Inhibition of RSK1 or siRNA-mediated
      silencing of RSK1 attenuates H/R-induced apoptosis, demonstrating the role of
      RSK1 in cardiomyocyte apoptosis. Furthermore, silencing of RSK1 decreases the H/R
      induced phosphorylation of sodium-hydrogen exchanger 1 (NHE1), and inhibition of
      NHE1 with 5'-N-ethyl-N-isopropyl-amiloride blocks H/R induced apoptosis,
      indicating the involvement of NHE1 in apoptosis. Overall, our findings
      demonstrate that H/R-mediated decrease in PKARIalpha protein levels leads to
      activation of RSK1, which via phosphorylation of NHE1 induces cardiomyocyte
      apoptosis. 

PMID- 24307702
TI  - HomSI: a homozygous stretch identifier from next-generation sequencing data.
AB  - In consanguineous families, as a result of inheriting the same genomic segments
      through both parents, the individuals have stretches of their genomes that are
      homozygous. This situation leads to the prevalence of recessive diseases among
      the members of these families. Homozygosity mapping is based on this observation,
      and in consanguineous families, several recessive disease genes have been
      discovered with the help of this technique. The researchers typically use single
      nucleotide polymorphism arrays to determine the homozygous regions and then
      search for the disease gene by sequencing the genes within this candidate disease
      loci. Recently, the advent of next-generation sequencing enables the concurrent
      identification of homozygous regions and the detection of mutations relevant for
      diagnosis, using data from a single sequencing experiment. In this respect, we
      have developed a novel tool that identifies homozygous regions using deep
      sequence data. Using *.vcf (variant call format) files as an input file, our
      program identifies the majority of homozygous regions found by microarray single
      nucleotide polymorphism genotype data. AVAILABILITY AND IMPLEMENTATION: HomSI
      software is freely available at www.igbam.bilgem.tubitak.gov.tr/softwares/HomSI,
      with an online manual.

PMID- 24307700
TI  - HEFT: eQTL analysis of many thousands of expressed genes while simultaneously
      controlling for hidden factors.
AB  - MOTIVATION: Identification of expression Quantitative Trait Loci (eQTL), the
      genetic loci that contribute to heritable variation in gene expression, can be
      obstructed by factors that produce variation in expression profiles if these
      factors are unmeasured or hidden from direct analysis. METHODS: We have developed
      a method for Hidden Expression Factor analysis (HEFT) that identifies individual
      and pleiotropic effects of eQTL in the presence of hidden factors. The HEFT model
      is a combined multivariate regression and factor analysis, where the complete
      likelihood of the model is used to derive a ridge estimator for simultaneous
      factor learning and detection of eQTL. HEFT requires no pre-estimation of hidden
      factor effects; it provides P-values and is extremely fast, requiring just a few
      hours to complete an eQTL analysis of thousands of expression variables when
      analyzing hundreds of thousands of single nucleotide polymorphisms on a standard
      8 core 2.6 G desktop. RESULTS: By analyzing simulated data, we demonstrate that
      HEFT can correct for an unknown number of hidden factors and significantly
      outperforms all related hidden factor methods for eQTL analysis when there are
      eQTL with univariate and multivariate (pleiotropic) effects. To demonstrate a
      real-world application, we applied HEFT to identify eQTL affecting gene
      expression in the human lung for a study that included presumptive hidden
      factors. HEFT identified all of the cis-eQTL found by other hidden factor methods
      and 91 additional cis-eQTL. HEFT also identified a number of eQTLs with direct
      relevance to lung disease that could not be found without a hidden factor
      analysis, including cis-eQTL for GTF2H1 and MTRR, genes that have been
      independently associated with lung cancer. AVAILABILITY: Software is available at
      http://mezeylab.cb.bscb.cornell.edu/Software.aspx. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 24307703
TI  - Cascade: a R package to study, predict and simulate the diffusion of a signal
      through a temporal gene network.
AB  - SUMMARY: Temporal gene interactions, in response to environmental stress, form a
      complex system that can be efficiently described using gene regulatory networks.
      They allow highlighting the more influential genes and spotting some targets for
      biological intervention experiments. Despite that many reverse engineering tools
      have been designed, the Cascade package is an integrated solution adding several
      new and original key features such as the ability to predict changes in gene
      expressions after a biological perturbation in the network and graphical outputs
      that allow monitoring the spread of a signal through the network. AVAILABILITY
      AND IMPLEMENTATION: The R package Cascade is available online at http://www
      math.u-strasbg.fr/genpred/spip.php?rubrique4.

PMID- 24307704
TI  - Joint estimation of isoform expression and isoform-specific read distribution
      using multisample RNA-Seq data.
AB  - MOTIVATION: RNA-sequencing technologies provide a powerful tool for expression
      analysis at gene and isoform level, but accurate estimation of isoform abundance
      is still a challenge. Standard assumption of uniform read intensity would yield
      biased estimates when the read intensity is in fact non-uniform. The problem is
      that, without strong assumptions, the read intensity pattern is not identifiable
      from data observed in a single sample. RESULTS: We develop a joint statistical
      model that accounts for non-uniform isoform-specific read distribution and gene
      isoform expression estimation. The main challenge is in dealing with the large
      number of isoform-specific read distributions, which potentially are as many as
      the number of splice variants in the genome. A statistical regularization via a
      smoothing penalty is imposed to control the estimation. Also, for identifiability
      reasons, the method uses information across samples from the same region. We
      develop a fast and robust computational procedure based on the iterated-weighted
      least-squares algorithm, and apply it to simulated data and two real RNA-Seq
      datasets with reverse transcription-polymerase chain reaction validation.
      Empirical tests show that our model performs better than existing methods in
      terms of increasing precision in isoform-level estimation. AVAILABILITY AND
      IMPLEMENTATION: We have implemented our method in an R package called Sequgio as
      a pipeline for fast processing of RNA-Seq data.

PMID- 24307705
TI  - Influence of lysophosphatidic acid on nitric oxide-induced luteolysis in
      steroidogenic luteal cells in cows.
AB  - Lysophosphatidic acid (LPA) together with its active G protein-coupled receptors
      are present in the corpus luteum (CL) of the cow. Under in vivo conditions, LPA
      stimulated P4 and PGE2 secretion during the luteal phase of the estrous cycle in
      heifers. Furthermore, LPA maintained P4 synthesis and actions in the bovine CL in
      vitro. However, the effect of this phospholipid on nitric oxide (NO)-induced
      functional and structural luteolysis has not been investigated. The aim of the
      present work was to determine the effects of LPA on 1) NO-induced functional
      luteolysis, 2) NO-dependent PG synthesis, and 3) NO-induced structural luteolysis
      in cultured steroidogenic luteal cells. We documented that LPA reversed the
      inhibitory effect of NONOate, an NO donor, on P4 synthesis and PGE2/PGF2alpha
      ratio in cultured steroidogenic luteal cells. Additionally, LPA inhibited NO
      induced apoptosis in cultured steroidogenic luteal cells via abrogation of the NO
      dependent stimulatory influence on proapoptotic TNFalpha/TNFR1 and Fas/FasL
      expression, Caspase 3 activity, and the Bax/Bcl2 ratio during luteal regression
      in the bovine CL. In conclusion, this study proves that in the presence of LPA,
      NO cannot induce luteolytic capacity acquisition, leading to functional and
      structural luteolysis of bovine luteal cells. 

PMID- 24307706
TI  - SPACA7 is a novel male germ cell-specific protein localized to the sperm acrosome
      that is involved in fertilization in mice.
AB  - Sperm acrosome associated 7 (SPACA7) is a novel protein of unknown function with
      no homology to any known protein. Spaca7 transcripts are detected only in testis
      and predict a 158-residue mature polypeptide with one potential N-glycosylation
      site and no cysteines. Orthologs are present in various species, including mice
      and humans. We developed a polyclonal antibody to mouse SPACA7 to study its
      expression and function. Western blotting and immunofluorescence microscopy
      detected SPACA7 only in testis, and it was detected in testis starting at
      Postnatal Day 21 and into adulthood. Immunofluorescence staining of testicular
      germ cells detected weak SPACA7 expression as early as zygotene spermatocytes.
      Higher expression was observed in round spermatids, where SPACA7 was localized to
      a perinuclear spot adjacent to the Golgi and to the acrosome of elongating
      spermatids and spermatozoa. Immunogold electron microscopy demonstrated that
      SPACA7 is localized within the proacrosomal granule of round spermatids and the
      acrosome of spermatozoa. Finally, we showed that SPACA7 was retained within the
      acrosome of epididymal sperm and was released upon the acrosome reaction. To
      assess if SPACA7 was involved in fertilization, in vitro fertilization assays in
      the presence of anti-SPACA7 IgG were performed. Anti-SPACA7 inhibited
      fertilization of cumulus-intact eggs and prominently delayed cumulus dispersal.
      However, anti-SPACA7 did not inhibit fertilization of cumulus-free eggs. Our
      findings indicate that release of SPACA7 from the acrosome accelerates cumulus
      dispersal and facilitates fertilization via unknown mechanisms. This study is the
      first to document the expression of endogenous SPACA7 and a function for this
      novel acrosomal protein. 

PMID- 24307707
TI  - Murine Binder of SPerm homolog 2 (BSPH2): the black sheep of the BSP superfamily.
AB  - Proteins of the Binder of SPerm superfamily are known to bind choline
      phospholipids on sperm membrane and promote sperm capacitation. The current study
      focuses on the biochemical and functional characterization of the murine Binder
      of SPerm homolog 2 (BSPH2). A recombinant protein (rec-BSPH2) was expressed in
      Escherichia coli Rosetta-gami B (DE3)pLysS cells using pET32a vector. It was
      purified by immobilized metal ion affinity chromatography and refolded on column
      using a decreasing urea gradient. Rec-BSPH2 was found to share some binding
      characteristics with other BSP proteins, such as binding to gelatin, heparin, and
      epididymal sperm. Rec-BSPH2 as well as murine recombinant BSPH1 were found to
      have different immunofluorescence patterns when bound to uncapacitated versus
      capacitated sperm, indicating a rearrangement of these proteins on sperm surface
      during or following capacitation. Surprisingly, rec-BSPH2 was unable to bind
      phosphorylcholine liposomes or promote sperm capacitation. It is the first time
      that such results are reported for proteins of the BSP family. The results
      indicate that murine BSPH1 and BSPH2 might not have redundant functions, as is
      the case with bovine BSPs. This study could lead to a better understanding of the
      role of BSP proteins in sperm functions and the existence of redundant BSP
      proteins in the reproductive tract. 

PMID- 24307708
TI  - A life in science: a celebration of the career of Hans Hoppeler at the University
      of Bern.

PMID- 24307709
TI  - Locomotion- and mechanics-mediated tactile sensing: antenna reconfiguration
      simplifies control during high-speed navigation in cockroaches.
AB  - Animals can expend energy to acquire sensory information by emitting signals
      and/or moving sensory structures. We propose that the energy from locomotion
      itself could permit control of a sensor, whereby animals use the energy from
      movement to reconfigure a passive sensor. We investigated high-speed, antenna
      mediated tactile navigation in the cockroach Periplaneta americana. We discovered
      that the passive antennal flagellum can assume two principal mechanical states,
      such that the tip is either projecting backward or forward. Using a combination
      of behavioral and robotic experiments, we demonstrate that a switch in the
      antenna's state is mediated via the passive interactions between the sensor and
      its environment, and this switch strongly influences wall-tracking control. When
      the tip of the antenna is projected backward, the animals maintain greater body
      to-wall distance with fewer body collisions and less leg-wall contact than when
      the tip is projecting forward. We hypothesized that distally pointing
      mechanosensory hairs at the tip of the antenna mediate the switch in state by
      interlocking with asperities in the wall surface. To test this hypothesis, we
      performed laser ablation of chemo-mechanosensory hairs and added artificial hairs
      to a robotic antenna. In both the natural and artificial systems, the presence of
      hairs categorically increased an antenna's probability of switching state.
      Antennal hairs, once thought to only play a role in sensing, are sufficient for
      mechanically reconfiguring the state of the entire antenna when coupled with
      forward motion. We show that the synergy between antennal mechanics, locomotion
      and the environment simplifies tactile sensing. 

PMID- 24307710
TI  - Proteomic response of marine invertebrate larvae to ocean acidification and
      hypoxia during metamorphosis and calcification.
AB  - Calcifying marine invertebrates with complex life cycles are particularly at risk
      to climate changes as they undergo an abrupt ontogenetic shift during larval
      metamorphosis. Although our understanding of the larval response to climate
      changes is rapidly advancing, the proteome plasticity involved in a compensatory
      response to climate change is still unknown. In this study, we investigated the
      proteomic response of metamorphosing larvae of the tubeworm Hydroides elegans,
      challenged with two climate change stressors, ocean acidification (OA; pH 7.6)
      and hypoxia (HYP; 2.8 mg O2 l(-1)), and with both combined. Using a two
      dimensional gel electrophoresis (2-DE)-based approach coupled with mass
      spectrometry, we found that climate change stressors did not affect metamorphosis
      except under OA, but altered the larval proteome and phosphorylation status.
      Metabolism and various stress and calcification-related proteins were
      downregulated in response to OA. In OA and HYP combined, HYP restored the
      expression of the calcification-related proteins to the control levels. We
      speculate that mild HYP stress could compensate for the negative effects of OA.
      This study also discusses the potential functions of selected proteins that might
      play important roles in larval acclimation and adaption to climate change. 

PMID- 24307711
TI  - The behavioural effects of predator-induced stress responses in the cricket
      (Gryllus texensis): the upside of the stress response.
AB  - Predator-induced stress responses are thought to reduce an animal's risk of being
      eaten. Therefore, these stress responses should enhance anti-predator behaviour.
      We found that individual insects (the cricket Gryllus texensis) show reliable
      behavioural responses (i.e. behavioural types) in a plus-shaped maze. An
      individual's behaviour in the plus maze remained consistent for at least 1/2 of
      its adult life. However, after exposure to a model predator, both male and female
      crickets showed a reduced period of immobility and an increased amount of time
      spent under shelter compared with controls. These changes could be mimicked by
      injections of the insect stress neurohormone octopamine. These behavioural
      changes probably aid crickets in evading predators. Exposure to a model predator
      increased the ability of crickets to escape a live predator (a bearded dragon,
      Pogona vitticeps). An injection of octopamine had the same effect, showing that
      stress hormones can reduce predation. Using crickets to study the fitness
      consequences of predator-induced stress responses will help integrate ecological
      and biomedical concepts of 'stress'. 

PMID- 24307712
TI  - Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and
      thyroid hormone receptor beta-1 in a fasting-adapted mammal.
AB  - Food deprivation in mammals is typically associated with reduced thyroid hormone
      (TH) concentrations and deiodinase content and activity to suppress metabolism.
      However, in prolonged-fasted, metabolically active elephant seal pups, TH levels
      are maintained, if not elevated. The functional relevance of this apparent
      paradox is unknown and demonstrates variability in the regulation of TH levels,
      metabolism and function in food-deprived mammals. To address our hypothesis that
      cellular TH-mediated activity is upregulated with fasting duration, we quantified
      the mRNA expression and protein content of adipose and muscle deiodinase type I
      (DI1) and type II (DI2), and TH receptor beta-1 (THrbeta-1) after 1, 3 and 7
      weeks of fasting in northern elephant seal pups (N=5-7 per week). Fasting did not
      decrease the concentrations of plasma thyroid stimulating hormone, total
      triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting
      that the hypothalamic-pituitary-thyroid axis is not suppressed, but rather
      maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased
      threefold and fourfold, respectively, and 20- and 30-fold, respectively, in
      muscle. With the exception of adipose DI1, protein expression of adipose DI2 and
      muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose
      (fivefold) and muscle (fourfold) THrbeta-1 mRNA expression, suggesting that the
      mechanisms mediating cellular TH activity are upregulated with prolonged fasting.
      The data demonstrate a unique, atypical mechanism of TH activity and regulation
      in mammals adapted to prolonged food deprivation in which the potential
      responsiveness of peripheral tissues and cellular TH activity are increased,
      which may contribute to their lipid-based metabolism. 

PMID- 24307713
TI  - Maintaining acoustic communication at a cocktail party: heterospecific masking
      noise improves signal detection through frequency separation.
AB  - We examined acoustic masking in a chirping katydid species of the Mecopoda
      elongata complex due to interference with a sympatric Mecopoda species where
      males produce continuous trills at high amplitudes. Frequency spectra of both
      calling songs range from 1 to 80 kHz; the chirper species has more energy in a
      narrow frequency band at 2 kHz and above 40 kHz. Behaviourally, chirper males
      successfully phase-locked their chirps to playbacks of conspecific chirps under
      masking conditions at signal-to-noise ratios (SNRs) of -8 dB. After the 2 kHz
      band in the chirp had been equalised to the level in the masking trill, the
      breakdown of phase-locked synchrony occurred at a SNR of +7 dB. The remarkable
      receiver performance is partially mirrored in the selective response of a first
      order auditory interneuron (TN1) to conspecific chirps under these masking
      conditions. However, the selective response is only maintained for a stimulus
      including the 2 kHz component, although this frequency band has no influence on
      the unmasked TN1 response. Remarkably, the addition of masking noise at 65 dB
      sound pressure level (SPL) to threshold response levels of TN1 for pure tones of
      2 kHz enhanced the sensitivity of the response by 10 dB. Thus, the spectral
      dissimilarity between masker and signal at a rather low frequency appears to be
      of crucial importance for the ability of the chirping species to communicate
      under strong masking by the trilling species. We discuss the possible properties
      underlying the cellular/synaptic mechanisms of the 'novelty detector'. 

PMID- 24307714
TI  - Cerebrospinal fluid pressure and glaucoma: regulation of trans-lamina cribrosa
      pressure.
AB  - Increased trans-lamina cribrosa pressure difference (TLCPD), the difference of
      intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSF-P), has
      been investigated as a possible risk factor in glaucoma pathogenesis. In fact,
      lower CSF-P in the setting of normal IOP has been implicated as a potential risk
      factor for normal tension glaucoma. Increased TLCPD has been associated with
      decreased neuroretinal rim area and increased visual field defects. Furthermore,
      dysregulation of systemic blood pressure has been associated with changes in IOP.
      Recent studies have also suggested that increased body mass index (BMI) is
      associated with decreased prevalence of glaucoma, which may be due to an
      increased CSF-P with increased BMI found in many studies. Given the interaction
      of various pressures, their role in glaucoma pathophysiology has come under
      investigation and warrants further study in order to better understand the
      aetiology and progression of glaucoma. 

PMID- 24307715
TI  - Can conjunctival lymphoma be a clinical diagnosis?

PMID- 24307716
TI  - Subfoveal choroidal thickness measurements with enhanced depth imaging optical
      coherence tomography in patients with nanophthalmos.
AB  - PURPOSE: To compare subfoveal choroidal thickness (SFCT) between patients with
      nanophthalmos and age-matched controls. METHODS: This prospective, cross
      sectional and comparative study included 31 eyes from 31 patients with
      nanophthalmos (study group) and 31 eyes from 31 healthy subjects (control group).
      SFCT and central macular thickness (CMT) were measured with spectral domain
      optical coherence tomography. All participants underwent a standardised ocular
      examination including best corrected visual acuity (BCVA), central corneal
      thickness (CCT), anterior chamber depth (ACD) and refractive error (RE)
      measurements. RESULTS: Mean SFCT in the nanophthalmic eyes and in the control
      eyes were 551.3 +/- 87 um and 330.5 +/- 46 um, respectively (p<0.001). Mean BCVA,
      RE, CMT, axial length (AL), ACD, CCT values were 0.4 +/- 0.28 logMAR Unit, +10.6
      (3.06), 331.9 +/- 78 um, 18.8 +/- 1.5 mm, 2.42 +/- 0.4 mm and 577.2 +/- 32 um,
      respectively, in nanophthalmic eyes and there was a statistically significant
      difference between groups (p<0.001 for each). There were negative correlations
      between SFCT with AL (r=-0.836, p<0.001) and ACD (r=-0.597, p<0.001) for the
      entire study population. SFCT was significantly correlated with CCT (r=0.471,
      p<0.001) and CMT (r=0.585, p<0.001), RE (r=0.836, p<0.001). CONCLUSIONS: SFCT was
      significantly higher in nanophthalmic eyes. Further studies are needed to
      evaluate the role of SFCT to explain the pathophysiology of nanophthalmos.

PMID- 24307717
TI  - Reproducibility of macular ganglion cell-inner plexiform layer thickness
      measurement with cirrus HD-OCT in normal, hypertensive and glaucomatous eyes.
AB  - AIM: To evaluate the intraobserver and interobserver reproducibility of macular
      retinal ganglion cell-inner plexiform layer (GC-IPL) thickness measurement by
      automated detection on Optical Coherence Tomography (OCT) images in normal,
      hypertensive (ocular hypertensive (OHT)) and glaucomatous eyes. METHODS: A total
      of 138 eyes were enrolled in three groups: 69 normal, 35 OHT and 34 primary open
      angle glaucoma eyes. All patients underwent a complete ocular examination, 24-2
      automated perimetry, biometry and pachymetry. Macular imaging was performed in
      each eye using the Cirrus HD-OCT 4000 with software V.6.0. (Carl Zeiss Meditec,
      Dublin, California, USA) three times on the same day by each of two observers,
      and the GC analysis (GCA) algorithm provided parameters expressed as average,
      minimum and six sectoral GC-IPL thicknesses. Reproducibility was assessed by
      intraclass correlation coefficient (ICC), coefficient of variation (CV) and test
      retest variability (TRTV) calculated as 1.96 times the SD. RESULTS: Mean GC-IPL
      thickness was 82.27 +/- 7.37 MUm, 76.84 +/- 7.01 MUm and 66.16 +/- 11.16 MUm in
      normal, OHT and glaucoma groups, respectively. GC-IPL thickness was significantly
      lower in glaucomatous eyes than in normal and OHT eyes (p<0.0001 for all
      parameters). In all groups, ICC ranged from 96.4 to 99.9% and 92.5 to 99.8%, CV
      ranged from 0.41 to 2.24% and 0.55 to 1.67%, and TRTV ranged from 0.61 to 2.64
      MUm and 0.83 to 2.22 MUm for intraobserver and interobserver reproducibility,
      respectively. CONCLUSIONS: To the best of our knowledge, this is the first study
      of GCA algorithm reproducibility in normal, OHT and glaucomatous eyes. The
      reproducibility of GC-IPL thickness measurements using the Cirrus HD-OCT GCA
      algorithm was found to be highly satisfactory. GC-IPL thickness may be a
      promising new OCT parameter for analysis of ganglion cell damage in glaucoma.

PMID- 24307718
TI  - Expanding roles of protein kinase CK2 in regulating plant growth and development.
AB  - Protein kinase CK2 (formerly known as casein kinase II) is a ubiquitious Ser/Thr
      kinase present in all eukaryotes. The alpha (catalytic) and beta (regulatory)
      subunits of CK2 exist both as a tetrameric holoenzyme and as monomers in
      eukaryotic cells. CK2 has been implicated in multiple developmental and stress
      responsive pathways including light signalling and circadian clock in plants.
      Recent studies using CK2 knockout and dominant negative mutants in Arabidopsis
      have uncovered new roles for this enzyme. CK2 substrates that have been
      identified so far are primarily transcription factors or regulatory proteins. CK2
      mediated phosphorylation of these factors often results in alteration of the
      protein function including changes in the DNA-binding affinity, dimerization,
      stability, protein-protein interactions, and subcellular localization. CK2 has
      evolved as an essential housekeeping kinase in plants that modifies protein
      function in a dynamic way. This review summarizes the current knowledge of the
      role of CK2 in plant development. 

PMID- 24307719
TI  - Early competition shapes maize whole-plant development in mixed stands.
AB  - Mixed cropping is practised widely in developing countries and is gaining
      increasing interest for sustainable agriculture in developed countries. Plants in
      intercrops grow differently from plants in single crops, due to interspecific
      plant interactions, but adaptive plant morphological responses to competition in
      mixed stands have not been studied in detail. Here the maize (Zea mays) response
      to mixed cultivation with wheat (Triticum aestivum) is described. Evidence is
      provided that early responses of maize to the modified light environment in mixed
      stands propagate throughout maize development, resulting in different phenotypes
      compared with pure stands. Photosynthetically active radiation (PAR), red:far-red
      ratio (R:FR), leaf development, and final organ sizes of maize grown in three
      cultivation systems were compared: pure maize, an intercrop with a small distance
      (25cm) between maize and wheat plants, and an intercop with a large distance
      (44cm) between the maize and the wheat. Compared with maize in pure stands, maize
      in the mixed stands had lower leaf and collar appearance rates, increased blade
      and sheath lengths at low ranks and smaller sizes at high ranks, increased blade
      elongation duration, and decreased R:FR and PAR at the plant base during early
      development. Effects were strongest in the treatment with a short distance
      between wheat and maize strips. The data suggest a feedback between leaf
      initiation and leaf emergence at the plant level and coordination between blade
      and sheath growth at the phytomer level. A conceptual model, based on
      coordination rules, is proposed to explain the development of the maize plant in
      pure and mixed stands. 

PMID- 24307720
TI  - The ASH Choosing Wisely(r) campaign: five hematologic tests and treatments to
      question.
AB  - Choosing Wisely(r) is a medical stewardship and quality improvement initiative
      led by the American Board of Internal Medicine Foundation in collaboration with
      leading medical societies in the United States. The ASH is an active participant
      in the Choosing Wisely(r) project. Using an iterative process and an evidence
      based method, ASH has identified 5 tests and treatments that in some
      circumstances are not well supported by evidence and which in certain cases
      involve a risk of adverse events and financial costs with low likelihood of
      benefit. The ASH Choosing Wisely(r) recommendations focus on avoiding liberal RBC
      transfusion, avoiding thrombophilia testing in adults in the setting of transient
      major thrombosis risk factors, avoiding inferior vena cava filter usage except in
      specified circumstances, avoiding the use of plasma or prothrombin complex
      concentrate in the nonemergent reversal of vitamin K antagonists, and limiting
      routine computed tomography surveillance after curative-intent treatment of non
      Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated
      benefits of the identified tests and treatments before performing them.

PMID- 24307721
TI  - Identification of Bruton's tyrosine kinase as a therapeutic target in acute
      myeloid leukemia.
AB  - Bruton's tyrosine kinase (BTK) is a cytoplasmic protein found in all
      hematopoietic cell lineages except for T cells. BTK mediates signaling downstream
      of a number of receptors. Pharmacologic targeting of BTK using ibrutinib
      (previously PCI-32765) has recently shown encouraging clinical activity in a
      range of lymphoid malignancies. This study reports for the first time that
      ibrutinib inhibits blast proliferation from human acute myeloid leukemia (AML)
      and that treatment with ibrutinib significantly augmented cytotoxic activities of
      standard AML chemotherapy cytarabine or daunorubicin. Here we describe that BTK
      is constitutively phosphorylated in the majority of AML samples tested, with BTK
      phosphorylation correlating highly with the cell's cytotoxic sensitivity toward
      ibrutinib. BTK-targeted RNAi knockdown reduced colony-forming capacity of primary
      AML blasts and proliferation of AML cell lines. We showed that ibrutinib binds at
      nanomolar range to BTK. Furthermore, we showed ibrutinib's antiproliferative
      effects in AML are mediated via an inhibitory effect on downstream nuclear factor
      kappaB survival pathways. Moreover, ibrutinib inhibited AML cell adhesion to bone
      marrow stroma. Furthermore, these effects of ibrutinib in AML were seen at
      comparable concentrations efficacious in chronic lymphocytic leukemia. These
      results provide a biological rationale for clinical evaluation of BTK inhibition
      in AML patients. 

PMID- 24307722
TI  - Evidence grows for benefits of exercise in dementia.

PMID- 24307723
TI  - Too much medicine: from evidence to action.

PMID- 24307724
TI  - A healthy market? Lack of transparency raises doubts about NHS commissioning.

PMID- 24307725
TI  - Tackling female genital mutilation in the UK.

PMID- 24307726
TI  - Dethroning the king of condiments: what is the link between salt, hypertension,
      and mortality?

PMID- 24307727
TI  - Rate of surgery for lung cancer in England and Wales rose 50% in five years.

PMID- 24307728
TI  - Scottish healthcare performs no better than England despite higher spending,
      report finds.

PMID- 24307729
TI  - Cognate peptide-MHC complexes are expressed as tightly apposed nanoclusters in
      virus-infected cells to allow TCR crosslinking.
AB  - Antigenic T cell stimulation requires interaction between the TCR of the T cell
      and cognate peptide-MHC molecules presented by the APC. Although studies with TCR
      specific Abs and soluble peptide-MHC ligands have shown that the TCR needs to be
      crosslinked by two or more ligands to induce T cell stimulation, it is not
      understood how several MHC molecules loaded with the cognate antigenic peptide
      can produce crosslinking under physiological conditions. We show at the molecular
      level that large clusters of cognate peptide-MHC are formed at the surface of
      murine professional and nonprofessional APCs upon virus infection and that these
      clusters impinge on the stimulatory capacity of the APC. These clusters are
      formed by tight apposition of cognate peptide-MHC complexes in a configuration
      that is compatible with simultaneous engagement of two or more TCRs. This
      suggests that physiological expression of Ag allows formation of multivalent
      ligands for the TCR that permit TCR crosslinking and T cell activation. 

PMID- 24307730
TI  - Th1 polarization of T cells injected into the cerebrospinal fluid induces brain
      immunosurveillance.
AB  - Although CD4 T cells reside within the cerebrospinal fluid, it is yet unclear
      whether and how they enter the brain parenchyma and migrate to target specific
      Ags. We examined the ability of Th1, Th2, and Th17 CD4 T cells injected
      intracerebroventricularly to migrate from the lateral ventricles into the brain
      parenchyma in mice. We show that primarily Th1 cells cross the ependymal layer of
      the ventricle and migrate within the brain parenchyma by stimulating an IFN-gamma
      dependent dialogue with neural cells, which maintains the effector function of
      the T cells. When injected into a mouse model of Alzheimer's disease, amyloid
      beta (Abeta)-specific Th1 cells target Abeta plaques, increase Abeta uptake, and
      promote neurogenesis with no evidence of pathogenic autoimmunity or neuronal
      loss. Overall, we provide a mechanistic insight to the migration of cerebrospinal
      fluid CD4 T cells into the brain parenchyma and highlight implications on brain
      immunity and repair. 

PMID- 24307731
TI  - A circadian clock gene, Rev-erbalpha, modulates the inflammatory function of
      macrophages through the negative regulation of Ccl2 expression.
AB  - Disruption of the circadian rhythm is a contributory factor to clinical and
      pathophysiological conditions, including cancer, the metabolic syndrome, and
      inflammation. Chronic and systemic inflammation are a potential trigger of type 2
      diabetes and cardiovascular disease and are caused by the infiltration of large
      numbers of inflammatory macrophages into tissue. Although recent studies
      identified the circadian clock gene Rev-erbalpha, a member of the orphan nuclear
      receptors, as a key mediator between clockwork and inflammation, the molecular
      mechanism remains unknown. In this study, we demonstrate that Rev-erbalpha
      modulates the inflammatory function of macrophages through the direct regulation
      of Ccl2 expression. Clinical conditions associated with chronic and systemic
      inflammation, such as aging or obesity, dampened Rev-erbalpha gene expression in
      peritoneal macrophages from C57BL/6J mice. Rev-erbalpha agonists or
      overexpression of Rev-erbalpha in the murine macrophage cell line RAW264
      suppressed the induction of Ccl2 following an LPS endotoxin challenge. We
      discovered that Rev-erbalpha represses Ccl2 expression directly through a Rev
      erbalpha-binding motif in the Ccl2 promoter region. Rev-erbalpha also suppressed
      CCL2-activated signals, ERK and p38, which was recovered by the addition of
      exogenous CCL2. Further, Rev-erbalpha impaired cell adhesion and migration, which
      are inflammatory responses activated through the ERK- and p38-signaling pathways,
      respectively. Peritoneal macrophages from mice lacking Rev-erbalpha display
      increases in Ccl2 expression. These data suggest that Rev-erbalpha regulates the
      inflammatory infiltration of macrophages through the suppression of Ccl2
      expression. Therefore, Rev-erbalpha may be a key link between aging- or obesity
      associated impairment of clockwork and inflammation. 

PMID- 24307732
TI  - Expansion of CMV-mediated NKG2C+ NK cells associates with the development of
      specific de novo malignancies in liver-transplanted patients.
AB  - Solid cancers are a major adverse outcome of orthotopic liver transplantation
      (OLT). Although the use of chronic immunosuppression is known to play a role in T
      cell impairment, recent insights into the specificities of NK cells led us to
      reassess the potential modulation of this innate immune cell compartment after
      transplantation. Our extensive phenotypic and functional study reveals that the
      development of specific de novo noncutaneous tumors post-OLT is linked to unusual
      NK cell subsets with maturation defects and to uncommon cytokine production
      associated with the development of specific cancers. Remarkably, in CMV(+)
      patients, the development de novo head/neck or colorectal tumors is linked to an
      aberrant expansion of NK cells expressing NKG2C and a high level of intracellular
      TNF-alpha, which impact on their polyfunctional capacities. In contrast, NK cells
      from patients diagnosed with genitourinary tumors possessed a standard immature
      signature, including high expression of NKG2A and a robust production of IFN
      gamma. Taken together, our results suggest that under an immunosuppressive
      environment, the interplay between the modulation of NK repertoire and CMV status
      may greatly hamper the spectrum of immune surveillance and thus favor outgrowth
      and the development of specific de novo tumors after OLT. 

PMID- 24307734
TI  - A novel T cell subset with trans-rearranged Vgamma-Cbeta TCRs shows Vbeta
      expression is dispensable for lineage choice and MHC restriction.
AB  - alphabeta T cells, which express the alpha-beta TCR heterodimer, express CD4 or
      CD8 coreceptors on cells that are MHC class I or MHC class II dependent. In
      contrast, gammadelta T cells do not express CD4 or CD8 and develop independently
      of MHC interaction. The factors that determine alphabeta and gammadelta lineage
      choice are not fully understood, and the determinants of MHC restriction of TCR
      specificity have been controversial. In this study we have identified a naturally
      occurring population of T cells expressing Vgamma-Cbeta receptor chains on the
      cell surface, the products of genomic trans-rearrangement between the Vgamma2
      gene and a variety of Dbeta or Jbeta genes, in place of an intact TCRbeta-chain
      and in association with TCRalpha. Identification of this population allowed an
      analysis of the role of TCR variable regions in determining T cell lineage choice
      and MHC restriction. We found that Vgamma2(+)Cbeta(+) cells are positive for
      either CD4 or CD8 and are selected in an MHC class II- or MHC class I-dependent
      manner, respectively, thus following the differentiation pathway of alphabeta and
      not gammadelta cells and demonstrating that Vbeta V region sequences are not
      required for selection of an MHC-restricted repertoire. 

PMID- 24307733
TI  - Calcium signaling via Orai1 is essential for induction of the nuclear orphan
      receptor pathway to drive Th17 differentiation.
AB  - Orai1 is the pore subunit of Ca(2+) release-activated Ca(2+) (CRAC) channels that
      stimulate downstream signaling pathways crucial for T cell activation. CRAC
      channels are an attractive therapeutic target for alleviation of autoimmune
      diseases. Using high-throughput chemical library screening targeting Orai1, we
      identified a novel class of small molecules that inhibit CRAC channel activity.
      One of these molecules, compound 5D, inhibited CRAC channel activity by blocking
      ion permeation. When included during differentiation, Th17 cells showed higher
      sensitivity to compound 5D than Th1 and Th2 cells. The selectivity was
      attributable to high dependence of promoters of retinoic-acid-receptor-related
      orphan receptors on the Ca(2+)-NFAT pathway. Blocking of CRAC channels
      drastically decreased recruitment of NFAT and histone modifications within key
      gene loci involved in Th17 differentiation. The impairment in Th17
      differentiation by treatment with CRAC channel blocker was recapitulated in Orai1
      deficient T cells, which could be rescued by exogenous expression of retinoic
      acid-receptor-related orphan receptors or a constitutive active mutant of NFAT.
      In vivo administration of CRAC channel blockers effectively reduced the severity
      of experimental autoimmune encephalomyelitis by suppression of differentiation of
      inflammatory T cells. These results suggest that CRAC channel blockers can be
      considered as chemical templates for the development of therapeutic agents to
      suppress inflammatory responses. 

PMID- 24307735
TI  - A single amino acid substitution in the hemagglutinin of H3N2 subtype influenza A
      viruses is associated with resistance to the long pentraxin PTX3 and enhanced
      virulence in mice.
AB  - The long pentraxin, pentraxin 3 (PTX3), can play beneficial or detrimental roles
      during infection and disease by modulating various aspects of the immune system.
      There is growing evidence to suggest that PTX3 can mediate antiviral activity in
      vitro and in vivo. Previous studies demonstrated that PTX3 and the short
      pentraxin serum amyloid P express sialic acids that are recognized by the
      hemagglutinin (HA) glycoprotein of certain influenza A viruses (IAV), resulting
      in virus neutralization and anti-IAV activity. In this study, we demonstrate that
      specificity of both HA and the viral neuraminidase for particular sialic acid
      linkages determines the susceptibility of H1N1, H3N2, and H7N9 strains to the
      antiviral activities of PTX3 and serum amyloid P. Selection of H3N2 virus mutants
      resistant to PTX3 allowed for identification of amino acid residues in the
      vicinity of the receptor-binding pocket of HA that are critical determinants of
      sensitivity to PTX3; this was supported by sequence analysis of a range of H3N2
      strains that were sensitive or resistant to PTX3. In a mouse model of infection,
      the enhanced virulence of PTX3-resistant mutants was associated with increased
      virus replication and elevated levels of proinflammatory cytokines in the
      airways, leading to pulmonary inflammation and lung injury. Together, these
      studies identify determinants in the viral HA that can be associated with
      sensitivity to the antiviral activities of PTX3 and highlight its importance in
      the control of IAV infection. 

PMID- 24307736
TI  - The response of secondary genes to lipopolysaccharides in macrophages depends on
      histone deacetylase and phosphorylation of C/EBPbeta.
AB  - LPS induces the expression of NO synthase 2 (nos2) in macrophages. The expression
      of this molecule is one of the hallmarks of classical activation. In this paper,
      we describe that trichostatin A (TSA), which inhibits deacetylase activity,
      blocks LPS-dependent nos2 expression. TSA specifically inhibits LPS-dependent
      genes of secondary response, which require new protein synthesis for their
      induction but not those belonging to the primary response, which do not depend on
      this process. Deacetylase activity acts at the transcriptional level because RNA
      polymerase II was not bound after LPS stimulus when we added TSA. A link between
      the global acetylation caused by HDAC inhibitor and gene promoter recruitment of
      CDK8 was found. This Mediator complex subunit associates with Med 12, Med13, and
      cyclin C to form a submodule that is a transcriptional negative regulator. We
      also found that TSA reduces C/EBPbeta phosphorylation without affecting its
      binding to DNA. Taken together, these results shed light on the molecular
      mechanisms involved in the transcriptional regulation of LPS-treated macrophages
      and on how TSA targets critical LPS-induced genes, such as nos2 and tnf-alpha, in
      inflammatory macrophage response. 

PMID- 24307737
TI  - Polymorphisms in the CD1d promoter that regulate CD1d gene expression are
      associated with impaired NKT cell development.
AB  - CD1d-restricted NKT cells comprise an innate-like T cell population that exerts
      significant influence over early events in the developing immune response. The
      frequency of NKT cells is highly variable in humans and in mice, but the basis
      for this variability remains unclear. In this study, we report a striking
      deficiency of type I NKT cells in the wild-derived inbred strains PWD/PhJ,
      SPRET/EiJ, and CAST/EiJ. Investigation of the underlying basis for the lack of
      type I NKT cells revealed that one strain, PWD/PhJ, exhibited a significant
      impairment in thymocyte and splenocyte CD1d gene and protein expression.
      Accordingly, both thymocytes and bone marrow-derived dendritic cells from PWD
      mice exhibited a significant impairment in the ability to present alpha
      galactosylceramide to NKT cells. The impaired PWD CD1d gene expression was due to
      impaired CD1d promoter activity. Fine-mapping of the promoter activity revealed
      that two single nucleotide substitutions at positions -331 and -164 in the
      proximal promoter were each sufficient to account for the diminished PWD CD1d
      promoter activity. Examination of the strain distribution pattern of these
      polymorphisms revealed that, of 19 strains analyzed, only PWD and PWK mice
      possessed both CD1d promoter polymorphisms. A subsequent examination of the PWK
      strain revealed that it also exhibited impaired thymocyte CD1d expression and
      very low numbers of NKT cells. Taken together, these results provide new insight
      into the control of CD1d gene expression, and they have implications for the
      evolution of CD1d and type I NKT cells. 

PMID- 24307738
TI  - Platelet-secreted microRNA-223 promotes endothelial cell apoptosis induced by
      advanced glycation end products via targeting the insulin-like growth factor 1
      receptor.
AB  - Platelets play a significant role in atherosclerosis, stroke, and asthma through
      active interaction with neutrophils, monocytes, and vascular endothelial cells.
      The mechanism underlying these intercellular interactions, however, is
      incompletely understood. In this study, we report that platelets can remotely
      modulate vascular endothelial cell apoptosis through releasing microRNA-223 (miR
      223)-containing microvesicles (MVs). First, platelets expressed abundant miRNAs,
      and miR-223 had the highest level of expression. Platelet miR-223 and other
      miRNAs can be upregulated by the stimulation with thrombopoietin (TPO) or
      thrombin. Unlike leukocytes, platelets contained high levels of pre-miRNAs, and
      upregulation of mature platelet miRNAs by TPO was correlated with decreased pre
      miRNAs. Second, under stimulation with TPO, platelets released a large amount of
      MVs, which also contain higher levels of miR-223. Elevation of miR-223 inside
      circulating platelet MVs (P-MVs) was also observed in plasma samples from
      patients with enteritis, hepatitis, nephritis, or atherosclerosis. Third,
      incubation of P-MVs with HUVECs, which had significantly lower levels of miR-223
      than platelets, showed that P-MVs effectively delivered miR-223 into HUVECs.
      Finally, in HUVECs, exogenous platelet miR-223 decreased the level of insulin
      like growth factor 1 receptor and thus promoted HUVEC apoptosis induced by
      advanced glycation end products. The proapoptotic effect of P-MVs on HUVECs was
      largely abolished by depleting cellular miR-223 using anti-miR-223 antisense
      oligonucleotide. In conclusion, our study presents the first evidence, to our
      knowledge, that platelet-released miR-223 promotes advanced glycation end product
      induced vascular endothelial cell apoptosis via targeting insulin-like growth
      factor 1 receptor. 

PMID- 24307739
TI  - MPYS/STING-mediated TNF-alpha, not type I IFN, is essential for the mucosal
      adjuvant activity of (3'-5')-cyclic-di-guanosine-monophosphate in vivo.
AB  - The bacterial second messenger (3'-5')-cyclic-di-guanosine-monophosphate (CDG) is
      a promising mucosal adjuvant candidate that activates balanced Th1/Th2/Th17
      responses. We showed previously that CDG activates stimulator of IFN genes
      (STING)-dependent IFN-I production in vitro. However, it is unknown whether STING
      or IFN-I is required for the CDG adjuvant activity in vivo. In this study, we
      show that STING(-/-) mice (Tmem173(<tm1Camb>)) do not produce Ag-specific Abs or
      Th1/Th2/Th17 cytokines during CDG/Ag immunization. Intranasal administration of
      CDG did not induce TNF-alpha, IL-1beta, IL-6, IL-12, or MCP-1 production in
      STING(-/-) mice. Surprisingly, we found that the cytokine and Ab responses were
      unaltered in CDG/Ag-immunized IFNAR(-/-) mice. Instead, we found that CDG
      activates STING-dependent, IFN-I-independent TNF-alpha production in vivo and in
      vitro. Furthermore, using a TNFR1(-/-) mouse, we demonstrate that TNF-alpha
      signaling is critical for CDG-induced Ag-specific Ab and Th1/Th2 cytokine
      production. This is distinct from STING-mediated DNA adjuvant activity, which
      requires IFN-I, but not TNF-alpha, production. Finally, we found that CDG
      activates STING-dependent, but IRF3 stimulation-independent, NF-kappaB signaling.
      Our results established an essential role for STING-mediated TNF-alpha production
      in the mucosal adjuvant activity of CDG in vivo and revealed a novel IFN-I
      stimulation-independent STING-NF-kappaB-TNF-alpha pathway. 

PMID- 24307740
TI  - Massive benefits of antiretroviral therapy in Africa.

PMID- 24307741
TI  - The survival benefits of antiretroviral therapy in South Africa.
AB  - BACKGROUND: We sought to quantify the survival benefits attributable to
      antiretroviral therapy (ART) in South Africa since 2004. METHODS: We used the
      Cost-Effectiveness of Preventing AIDS Complications-International model (CEPAC)
      to simulate 8 cohorts of human immunodeficiency virus (HIV)-infected patients
      initiating ART each year during 2004-2011. Model inputs included cohort-specific
      mean CD4(+) T-cell count at ART initiation (112-178 cells/uL), 24-week ART
      suppressive efficacy (78%), second-line ART availability (2.4% of ART
      recipients), and cohort-specific 36-month retention rate (55%-71%). CEPAC
      simulated survival twice for each cohort, once with and once without ART. The sum
      of the products of per capita survival differences and the total numbers of
      persons initiating ART for each cohort yielded the total survival benefits.
      RESULTS: Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years
      across the 8 cohorts. Total estimated population lifetime survival benefit for
      all persons starting ART during 2004-2011 was 21.7 million life-years, of which
      2.8 million life-years (12.7%) had been realized by December 2012. By 2030,
      benefits reached 17.9 million life-years under current policies, 21.7 million
      life-years with universal second-line ART, 23.3 million life-years with increased
      linkage to care of eligible untreated patients, and 28.0 million life-years with
      both linkage to care and universal second-line ART. CONCLUSIONS: We found
      dramatic past and potential future survival benefits attributable to ART,
      justifying international support of ART rollout in South Africa.

PMID- 24307743
TI  - A New Positioning Algorithm for Position-Sensitive Avalanche Photodiodes.
AB  - We are using a novel position sensitive avalanche photodiode (PSAPD) for the
      construction of a high resolution positron emission tomography (PET) camera. Up
      to now most researchers working with PSAPDs have been using an Anger-like
      positioning algorithm involving the four corner readout signals of the PSAPD.
      This algorithm yields a significant non-linear spatial "pin-cushion" distortion
      in raw crystal positioning histograms. In this paper, we report an improved
      positioning algorithm, which combines two diagonal corner signals of the PSAPD
      followed by a 45 degrees  rotation to determine the X or Y position of the
      interaction. We present flood positioning histogram data generated with the old
      and new positioning algorithms using a 3 * 4 array of 2 * 2 * 3 mm3 and a 3 * 8
      array of 1 * 1 * 3 mm3 of LSO crystals coupled to 8 * 8 mm2 PSAPDs. This new
      algorithm significantly reduces the pin-cushion distortion in raw flood histogram
      image.

PMID- 24307742
TI  - Molecular characterization of an invasive phenotype of group A Streptococcus
      arising during human infection using whole genome sequencing of multiple isolates
      from the same patient.
AB  - Invasive group A streptococcal (GAS) strains often have genetic differences
      compared to GAS strains from nonsterile sites. Invasive, "hypervirulent" GAS
      strains can arise from a noninvasive progenitor following subcutaneous
      inoculation in mice, but such emergence has been rarely characterized in humans.
      We used whole genome analyses of multiple GAS isolates from the same patient to
      document the molecular basis for emergence of a GAS strain with an invasive
      phenotype during human infection. In contrast to previous theories, we found that
      elimination of production of the cysteine protease SpeB was not necessary for
      emergence of GAS with an invasive, "hypervirulent" phenotype. 

PMID- 24307744
TI  - Spermatozoa Production by Triploid Males in the New Zealand Freshwater Snail
      Potamopyrgus antipodarum.
AB  - Asexual lineages derived from dioecious taxa are typically assumed to be all
      female. Even so, asexual females from a variety of animal taxa occasionally
      produce males. The existence of these males sets the stage for potential gene
      flow across asexual lineages as well as between sexual and asexual lineages. A
      recent study showed that asexual triploid female Potamopyrgus antipodarum, a New
      Zealand freshwater snail often used as a model to study sexual reproduction,
      occasionally produce triploid male offspring. Here, we show that these triploid
      male P. antipodarum 1) have testes that produce morphologically normal sperm, 2)
      make larger sperm cells that contain more nuclear DNA than the sperm produced by
      diploid sexual males, and 3) produce sperm that range in DNA content from haploid
      to diploid, and are often aneuploid. Analysis of meiotic chromosomes of triploid
      males showed that aberrant pairing during prophase I likely accounts for the high
      variation in DNA content among sperm. These results indicate that triploid male
      P. antipodarum produce sperm, but the extent to which these sperm are able to
      fertilize female ova remains unclear. Our results also suggest that the general
      assumption of sterility in triploid males should be more closely examined in
      other species in which such males are occasionally produced.

PMID- 24307745
TI  - Class Restricted Clustering and Micro-Perturbation for Data Privacy.
AB  - The extensive use of information technologies by organizations to collect and
      share personal data has raised strong privacy concerns. To respond to the
      public's demand for data privacy, a class of clustering-based data masking
      techniques is increasingly being used for privacy-preserving data sharing and
      analytics. Traditional clustering-based approaches for masking numeric
      attributes, while addressing re-identification risks, typically do not consider
      the disclosure risk of categorical confidential attributes. We propose a new
      approach to deal with this problem. The proposed method clusters data such that
      the data points within a group are similar in the non-confidential attribute
      values whereas the confidential attribute values within a group are well
      distributed. To accomplish this, the clustering method, which is based on a
      minimum spanning tree (MST) technique, uses two risk-utility tradeoff measures in
      the growing and pruning stages of the MST technique respectively. As part of our
      approach we also propose a novel cluster-level micro-perturbation method for
      masking data that overcomes a common problem of traditional clustering-based
      methods for data masking, which is their inability to preserve important
      statistical properties such as the variance of attributes and the covariance
      across attributes. We show that the mean vector and the covariance matrix of the
      masked data generated using the micro-perturbation method are unbiased estimates
      of the original mean vector and covariance matrix. An experimental study on
      several real-world datasets demonstrates the effectiveness of the proposed
      approach.

PMID- 24307746
TI  - BRIGHTENING THE BULB: RESPONSE TO COMMENTARY.

PMID- 24307747
TI  - Transient regional climate change: analysis of the summer climate response in a
      high-resolution, century-scale, ensemble experiment over the continental United
      States.
AB  - Integrating the potential for climate change impacts into policy and planning
      decisions requires quantification of the emergence of sub-regional climate
      changes that could occur in response to transient changes in global radiative
      forcing. Here we report results from a high-resolution, century-scale, ensemble
      simulation of climate in the United States, forced by atmospheric constituent
      concentrations from the Special Report on Emissions Scenarios (SRES) A1B
      scenario. We find that 21st century summer warming permanently emerges beyond the
      baseline decadal-scale variability prior to 2020 over most areas of the
      continental U.S. Permanent emergence beyond the baseline annual-scale variability
      shows much greater spatial heterogeneity, with emergence occurring prior to 2030
      over areas of the southwestern U.S., but not prior to the end of the 21st century
      over much of the southcentral and southeastern U.S. The pattern of emergence of
      robust summer warming contrasts with the pattern of summer warming magnitude,
      which is greatest over the central U.S. and smallest over the western U.S. In
      addition to stronger warming, the central U.S. also exhibits stronger coupling of
      changes in surface air temperature, precipitation, and moisture and energy
      fluxes, along with changes in atmospheric circulation towards increased
      anticylonic anomalies in the mid-troposphere and a poleward shift in the mid
      latitude jet aloft. However, as a fraction of the baseline variability, the
      transient warming over the central U.S. is smaller than the warming over the
      southwestern or northeastern U.S., delaying the emergence of the warming signal
      over the central U.S. Our comparisons with observations and the Coupled Model
      Intercomparison Project Phase 3 (CMIP3) ensemble of global climate model
      experiments suggest that near-term global warming is likely to cause robust sub
      regional-scale warming over areas that exhibit relatively little baseline
      variability. In contrast, where there is greater variability in the baseline
      climate dynamics, there can be greater variability in the response to elevated
      greenhouse forcing, decreasing the robustness of the transient warming signal.

PMID- 24307748
TI  - Using D-Amino Acids to Delineate the Mechanism of Protein Folding: Application to
      Trp-cage.
AB  - Using the miniprotein Trp-cage as a model, we show that D-amino acids can be used
      to facilitate the delineation of protein folding mechanism. Specifically, we
      study the folding-unfolding kinetics of three Trp-cage mutants where the native
      glycine residue near the C-terminus of the alpha-helix is replaced by a D-amino
      acid. A previous study showed that these mutations increase the Trp-cage
      stability, due to a terminal capping effect. Our results show that the
      stabilizing effect of D-asparagine and D-glutamine originates almost exclusively
      from a decrease in the unfolding rate, while the D-alanine mutation results in a
      similar decrease in the unfolding rate, but it also increases the folding rate.
      Together, these results support a folding mechanism wherein the alpha-helix
      formation in the transition state is nucleated at the N-terminus, whereas those
      long-range native interactions stabilizing this helix are developed at the
      downhill side of the folding free energy barrier.

PMID- 24307749
TI  - Some Distributions and Their Implications for an Internal Pilot Study With a
      Univariate Linear Model.
AB  - In planning a study, the choice of sample size may depend on a variance value
      based on speculation or obtained from an earlier study. Scientists may wish to
      use an internal pilot design to protect themselves against an incorrect choice of
      variance. Such a design involves collecting a portion of the originally planned
      sample and using it to produce a new variance estimate. This leads to a new power
      analysis and increasing or decreasing sample size. For any general linear
      univariate model, with fixed predictors and Gaussian errors, we prove that the
      uncorrected fixed sample F-statistic is the likelihood ratio test statistic.
      However, the statistic does not follow an F distribution. Ignoring the
      discrepancy may inflate test size. We derive and evaluate properties of the
      components of the likelihood ratio test statistic in order to characterize and
      quantify the bias. Most notably, the fixed sample size variance estimate becomes
      biased downward. The bias may inflate test size for any hypothesis test, even if
      the parameter being tested was not involved in the sample size re-estimation.
      Furthermore, using fixed sample size methods may create biased confidence
      intervals for secondary parameters and the variance estimate.

PMID- 24307752
TI  - Adult criminal involvement: A cross-sectional inquiry into correlates and
      mechanisms over the life course.
AB  - In this paper, we examine the relative contribution of four domains of predictors
      that have been linked to adult criminal involvement: (1) socio-demographic
      characteristics, (2) family-of-origin factors, (3) proximal processes developed
      during adolescence, and (4) current lifestyle and situational factors. Cross
      sectional data were collected through face-to-face interviews with 242 community
      recruited adults. Data analysis involved negative binomial regression. Being
      male, family size, juvenile delinquency, aggression, living with someone involved
      in illegal activity and recent violent victimization were independently
      associated with non-violent criminal involvement. Aggression, association with
      deviant peers, and recent violent victimization were independently associated
      with violent criminal involvement. Juvenile delinquency and aggression mediated
      the affect of multiple family-of-origin characteristics on non-violent criminal
      involvement and aggression mediated the effect of childhood physical abuse on
      violent criminal involvement. The results emphasize the importance of
      investigating both antecedents and proximal risk factors predictive of different
      types of criminal involvement, which, in turn, will assist in developing risk
      focused prevention and intervention programs.

PMID- 24307753
TI  - TREATMENT STAFF REFERRALS, PARTICIPATION EXPECTATIONS, AND PERCEIVED BENEFITS AND
      BARRIERS TO ADOLESCENT INVOLVEMENT IN 12-STEP GROUPS.
AB  - Adolescents treated for substance use disorders (SUD) appear to benefit from
      AA/NA participation. However, as compared to adults, fewer adolescents attend,
      and those who do attend do so less intensively and discontinue sooner. It is
      unknown whether this disparity is due to a lowered expectation for youth
      participation by the clinicians treating them, as they may adapt the adult-based
      model to fit a less dependent cohort, or whether recommendations are similar to
      those of clinicians who work with adults, and other factors are responsible. All
      clinical staff (N = 114) at five adolescent programs (3 residential, 2
      outpatient) were surveyed anonymously about referral practices and other beliefs
      about 12-step groups. Staff rated AA/NA participation as very important and
      helpful to adolescent recovery and referral rates were uniformly high (M = 86%,
      SD = 28%). Desired participation frequency was over 3 times per week. The
      theoretical orientation and level of care of the programs influenced some
      results. Findings suggest lower adolescent participation in 12-step groups is not
      due to a lack of clinician enthusiasm or referrals, but appears to be due to
      other factors.

PMID- 24307754
TI  - Statistical Modeling of RNA-Seq Data.
AB  - Recently, ultra high-throughput sequencing of RNA (RNA-Seq) has been developed as
      an approach for analysis of gene expression. By obtaining tens or even hundreds
      of millions of reads of transcribed sequences, an RNA-Seq experiment can offer a
      comprehensive survey of the population of genes (transcripts) in any sample of
      interest. This paper introduces a statistical model for estimating isoform
      abundance from RNA-Seq data and is flexible enough to accommodate both single end
      and paired end RNA-Seq data and sampling bias along the length of the transcript.
      Based on the derivation of minimal sufficient statistics for the model, a
      computationally feasible implementation of the maximum likelihood estimator of
      the model is provided. Further, it is shown that using paired end RNA-Seq
      provides more accurate isoform abundance estimates than single end sequencing at
      fixed sequencing depth. Simulation studies are also given.

PMID- 24307755
TI  - Dietary supplement ingredient database (DSID): Preliminary USDA studies on the
      composition of adult multivitamin/mineral supplements.
AB  - The Nutrient Data Laboratory of the United States Department of Agriculture
      (USDA) is collaborating with the Office of Dietary Supplements (ODS), the
      National Center for Health Statistics (NCHS), and other government agencies to
      design and populate a dietary supplement ingredient database (DSID). This
      analytically based, publicly available database will provide reliable estimates
      of vitamin and mineral content of dietary supplement (DS) products. The DSID will
      initially be populated with multivitamin/mineral (MVM) products because they are
      the most commonly consumed supplements. Challenges associated with the analysis
      of MVMs were identified and investigated. A pilot study addressing the
      identification of appropriate analytical methods, sample preparation protocols,
      and experienced laboratories for the analysis of 12 vitamins and 11 minerals in
      adult MVM supplement products was completed. Preliminary studies support the
      development of additional analytical studies with results that can be applied to
      the DSID. Total intakes from foods and supplements are needed to evaluate the
      associations between dietary components and health. The DSID will provide better
      estimates of actual nutrient intake from supplements than databases that rely on
      label values alone.

PMID- 24307756
TI  - Addressable, large-field second harmonic generation microscopy based on 2D
      acousto-optical deflector and spatial light modulator.
AB  - We present an addressable, large-field second harmonic generation microscope by
      combining a 2D acousto-optical deflector with a spatial light modulator. The SLM
      shapes an incoming mode-locked, near-infrared Ti:Sapphire laser beam into a
      multifocus array, which can be rapidly scanned by changing the incident angle of
      the laser beam using a 2D acousto-optical deflector. Compared to the single-beam
      scan technique, the multifocus array scan can increase the scanning rate and the
      field-of-view size with the multi-region imaging ability.

PMID- 24307757
TI  - The earliest sense of self and others: Merleau-Ponty and recent developmental
      studies.
AB  - Recent studies in developmental psychology have found evidence to suggest that
      there exists an innate system that accounts for the possibilities of early infant
      imitation and the existence of phantom limbs in cases of congenital absence of
      limbs. These results challenge traditional assumptions about the status and
      development of the body schema and body image, and about the nature of the
      translation process between perceptual experience and motor ability. Merleau
      Ponty, who was greatly influenced by his study of developmental psychology, and
      whose phenomenology of perception was closely tied to the concept of the body
      schema, accepted these traditional assumptions. They also informed his
      philosophical conclusions concerning the experience of self and others. We re
      examine issues involved in understanding self and others in light of the more
      recent research in developmental psychology. More specifically our re-examination
      challenges a number of Merleau-Ponty's conclusions and suggests, in contrast,
      that the newborn infant is capable of a rudimentary differentiation between self
      and non-self.

PMID- 24307758
TI  - Functional DNA directed assembly of nanomaterials for biosensing.
AB  - This review summarizes recent progress in the development of biosensors by
      integrating functional DNA molecules with different types of nanomaterials,
      including metallic nanoparticles, semiconductor nanoparticles, magnetic
      nanoparticles, and carbon nanotubes. On one hand, advances in nanoscale science
      and technology have generated nanomaterials with unique optical, electrical,
      magnetic and catalytic properties. On the other hand, recent progress in biology
      has resulted in functional DNAs, a new class of DNAs that can either bind to a
      target molecule (known as aptamers) or perform catalytic reactions (known as
      DNAzymes) with the ability to recognize a broad range of targets from metal ions
      to organic molecules, proteins and cells specifically. By taking advantage of the
      strengths in both fields, the physical and chemical properties of nanomaterials
      have been modulated by the target recognition and catalytic activity of
      functional DNAs in the presence of a target analyte, resulting in a large number
      of colorimetric, fluorescent, electrochemical, surface-enhanced Raman scattering
      and magnetic resonance imaging sensors for the detection of a broad range of
      analytes with high sensitivity and selectivity.

PMID- 24307759
TI  - Oncostatin M and TLR-4 ligand synergize to induce MCP-1, IL-6, and VEGF in human
      aortic adventitial fibroblasts and smooth muscle cells.
AB  - Accumulating evidence suggests that adventitial fibroblasts play a significant
      role in contributing to inflammation of the arterial wall and pathogenesis of
      atherosclerosis. The effects of gp130 cytokines on these cells (including
      oncostatin M-[OSM] and IL-6), some of which have been implicated in
      atherosclerosis, are currently unknown. Experiments were performed to determine
      whether gp130 cytokines regulate human aortic adventitial fibroblasts (HAoAFs) or
      smooth muscle cells (HAoSMCs) alone or in context of TLR-4 ligands (also
      implicated in atherosclerosis). HAoAFs and HAoSMCs were stimulated with LPS
      and/or one of OSM, IL-6, IL-11, IL-31, or LIF. ELISAs performed on cell
      supernatants showed that stimulation with OSM alone caused increased MCP-1, IL-6,
      and VEGF levels. When combined, LPS and OSM synergized to increase MCP-1, IL-6,
      VEGF protein, and mRNA expression as assessed by qRT-PCR, in both HAoAFs and
      HAoSMCs, while LPS-induced IL-8 levels were reduced. Such effects were not
      observed with other gp130 cytokines. Signalling pathways including STATs,
      MAPKinases, and NF kappa B were activated, and LPS induced steady state mRNA
      levels of the OSM receptor chains OSMR beta and gp130. The results suggest that
      OSM is able to synergize with TLR-4 ligands to induce proinflammatory responses
      by HAoAFs and HAoSMCs, supporting the notion that OSM regulation of these cells
      contributes to the pathogenesis of atherosclerosis. 

PMID- 24307760
TI  - Plasma granzyme B in ST elevation myocardial infarction versus non-ST elevation
      acute coronary syndrome: comparisons with IL-18 and fractalkine.
AB  - OBJECTIVE: The proapoptotic protein, granzyme B (GZB), was identified as a
      contributor to the atherosclerotic plaque instability and recently as
      inflammatory activator. We studied the release kinetics of GZB and other markers
      of inflammation such as high sensitivity C reactive protein (hsCRP), interleukin
      18 (IL-18), and fractalkine (FKN) in the early phase after acute cardiac events
      in different ACS subgroups. METHODS: Thirty-six nondiabetic patients with ACS
      were compared to 12 control subjects. According to ACS diagnosis, the patients
      were classified into 22 patients with ST elevation myocardial infarction (STEMI)
      and 14 patients with non-ST elevation myocardial infarction or unstable angina
      (NSTEMI/UA). Blood samples were taken on day 1 (day of onset) and day 3 to
      measure hsCRP, IL-18, FKN, and GZB by ELISA. RESULTS: Patients with ACS showed
      significantly higher GZB, IL-18, and FKN levels than the controls. STEMI group
      showed significantly higher GZB levels than NSTEMI/UA group. On day 3, FKN levels
      displayed a significant decrease, while GZB levels were significantly increased.
      IL-18 levels were more or less constant. GZB levels were positively correlated
      with IL-18 (r = 0.416, P < 0.01) and FKN (r = 0.58, P < 0.001). CONCLUSIONS:
      Unlike IL-18 and FKN, plasma GZB may be a marker of ACS disease severity.

PMID- 24307761
TI  - Asymmetric dimethylarginine blocks nitric oxide-mediated alcohol-stimulated cilia
      beating.
AB  - The airway epithelium is exposed to alcohol during drinking through direct
      exhalation of volatized ethanol from the bronchial circulation. Alcohol exposure
      leads to a rapid increase in the cilia beat frequency (CBF) of bronchial
      epithelial cells followed by a chronic desensitization of cilia stimulatory
      responses. This effect is governed in part by the nitric oxide regulation of
      cyclic guanosine and adenosine monophosphate-dependent protein kinases (PKG and
      PKA) and is not fully understood. Asymmetric dimethylarginine (ADMA), an
      endogenous inhibitor of nitric oxide synthase, is implicated in the pathogenesis
      of several pulmonary disorders. We hypothesized that the inhibition of nitric
      oxide synthase by ADMA blocks alcohol-stimulated increases in CBF. To test this
      hypothesis, ciliated primary bovine bronchial epithelial cells (BBEC) were
      preincubated with ADMA (100  uM) and stimulated with 100 mM ethanol. CBF was
      measured and PKA assayed. By 1 hr, ethanol activated PKA, resulting in elevated
      CBF. Both alcohol-induced PKA activation and CBF were inhibited in the presence
      of ADMA. ADMA alone had no effect on PKA activity or CBF. Using a mouse model
      overexpressing the ADMA-degrading enzyme, dimethylarginine dimethylaminohydrolase
      (DDAH), we examined PKA and CBF in precision-cut mouse lung slices. Alcohol
      stimulated increases in lung slice PKA and CBF were temporally enhanced in the
      DDAH mice versus control mice.

PMID- 24307762
TI  - Vitreous inflammation associated with intravitreal anti-VEGF pharmacotherapy.
AB  - Vascular endothelial growth factor (VEGF) is a potent promoter of angiogenesis
      involved in a wide variety of physiologic processes. Intravitreal injections
      targeting VEGF have transformed the treatment of neovascular retinal diseases.
      Currently, there are four anti-VEGF agents in use: bevacizumab, ranibizumab,
      pegaptanib, and aflibercept. The success and frequency of anti-VEGF therapy have
      made the ocular safety profile of these agents of vital importance. This paper
      focuses on sterile endophthalmitis. In this paper, we compare the incidences of
      posttreatment sterile endophthalmitis among the four agents, review the mechanism
      of actions, and discuss the most prevalent hypotheses leading to sterile
      endophthalmitis. 

PMID- 24307763
TI  - Retinal pigment epithelial cells express a functional receptor for glucagon-like
      peptide-1 (GLP-1).
AB  - Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that has been
      shown to improve glucose homeostasis in type 2 diabetes. The biological effects
      of GLP-1 are mediated by its specific receptor GLP-1R that is expressed in a wide
      range of tissues, where it is responsible of the extra-pancreatic effects of GLP
      1. Since the retinal pigment epithelium (RPE), that forms the outer retinal
      barrier, has a key role in protecting from diabetic retinopathy (DR), we
      investigated the potential expression and function of GLP-1R in a RPE cell line.
      ARPE-19 cells were cultured in DMEM/F12 supplemented with 10% FBS. The expression
      of GLP-1R was evaluated at both mRNA and protein levels. Then, the activation
      postreceptor intracellular signal transduction pathways (extracellular signal
      regulated kinases 1 and 2 [ERK1/2] and protein kinase B [PKB]) were assessed by
      western blot in normal cells or silenced for GLP-1R in the presence or absence of
      10 nmol/L GLP-1. The potential connections between intracellular signalling
      pathways triggered by GLP-1 stimulation were performed before incubating cells
      with kinase pharmacological inhibitors of mitogen-activated protein kinase
      (MEK)1/2, phosphatydilinositol-3kinase (PI3K), or epidermal growth factor
      receptor (EGFR). The results showed that GLP1R is expressed at both mRNA and
      protein level in ARPE-19 cells. Stimulation with GLP-1 strongly activated PKB and
      ERK1/2 phosphorylation till 40 min of exposure. GLP-1-mediated activation of both
      kinases was dependent on the upstream activation of PI3K and EGFR. Finally,
      treatment with GLP-1 did not affect the spontaneous release of VEGF-A from ARPE
      19 cells. In conclusion, this paper showed that the presence of functional GLP-1R
      is expressed in RPE cells. These data might represent the rationale to further
      investigate the potential direct beneficial effects of GLP-1 treatment against
      DR. 

PMID- 24307764
TI  - Mindfulness approaches to childbirth and parenting.
AB  - Mindfulness meditation is increasingly being used as a way of managing pain,
      reducing stress and anxiety and, in the form of mindfulness-based cognitive
      therapy (MBCT), as a way of reducing the risk of recurrence in depression (NICE,
      2004). This article considers its potential for parents preparing for childbirth
      focusing on three areas: managing pain during pregnancy and labour; reducing risk
      of perinatal depression; and increasing 'availability' of attention for the
      infant. The encouraging evidence to date suggests the possibility that
      mindfulness has an important contribution to make, both for reducing
      vulnerability in high-risk groups and as a universal intervention.

PMID- 24307765
TI  - Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2
      viral assembly.
AB  - Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease
      caused by dengue virus is a public health problem worldwide. The viral non
      structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication
      and hence, it is considered to be a good anti-viral target. Leaf extracts from
      Carica papaya is generally prescribed for patients with dengue fever, but there
      are no scientific evidences for its anti-dengue activity; hence we intended to
      investigate the anti-viral activity of compounds present in the leaves of Carica
      papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of
      the extracts from Carica papaya by using bioinformatics tools. Interestingly, we
      find the flavonoid quercetin with highest binding energy against NS2B-NS3
      protease which is evident by the formation of six hydrogen bonds with the amino
      acid residues at the binding site of the receptor. Our results suggest that the
      flavonoids from Carica papaya have significant anti-dengue activities.
      ABBREVIATIONS: ADME - Absorption, distribution, metabolism and excretion, BBB -
      Blood brain barrier, CYP - Cytochrome P450, DENV - - Dengue virus, DHF - Dengue
      hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - - Gas chromatography- Mass
      spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB 
      Protein data bank, PMF - Potential Mean Force.

PMID- 24307766
TI  - Evaluation of a duplex real-time PCR assay to detect MRSA from broth culture,
      human sera seeded with MRSA and from patient's serum.
AB  - The need for rapid methods in order to precisely detect methicillin-resistant
      Staphylococcus aureus (MRSA) is extensively acknowledged. This study evaluated a
      quantitative real-time PCR assay targeting mecA (encoding high level resistance
      to methicillin) and femB (a specific genomic marker for S. aureus) genes to
      detect MRSA from broth culture, from serum seeded with MRSA and straight from the
      patient's serum. One hundred and thirty-five clinical isolates of MRSA strains
      and different species were utilised in this study. In addition, a pilot study
      with 9 patients' serum samples was performed. The sensitivity and specificity
      values for this assay were 99% and 100% respectively. The detection limit for
      this method was 1.23*10(2) CFU/ml from the serum seeded with MRSA cells and the
      limiting concentration of DNA for detection was 18 fg, which equates to 5.14
      genomic DNA copies. In addition, this assay detected MRSA from patient's serum (7
      out of 9) with sensitivity of 77.8%. Overall, the assay was rapid, efficient,
      sensitive and easy to perform. 

PMID- 24307767
TI  - Domain wise docking analyses of the modular chitin binding protein CBP50 from
      Bacillus thuringiensis serovar konkukian S4.
AB  - This paper presents an in silico characterization of the chitin binding protein
      CBP50 from B. thuringiensis serovar konkukian S4 through homology modeling and
      molecular docking. The CBP50 has shown a modular structure containing an N
      terminal CBM33 domain, two consecutive fibronectin-III (Fn-III) like domains and
      a C-terminal CBM5 domain. The protein presented a unique modular structure which
      could not be modeled using ordinary procedures. So, domain wise modeling using
      MODELLER and docking analyses using Autodock Vina were performed. The best
      conformation for each domain was selected using standard procedure. It was
      revealed that four amino acid residues Glu-71, Ser-74, Glu-76 and Gln-90 from N
      terminal domain are involved in protein-substrate interaction. Similarly, amino
      acid residues Trp-20, Asn-21, Ser-23 and Val-30 of Fn-III like domains and Glu
      15, Ala-17, Ser-18 and Leu-35 of C-terminal domain were involved in substrate
      binding. Site-directed mutagenesis of these proposed amino acid residues in
      future will elucidate the key amino acids involved in chitin binding activity of
      CBP50 protein. 

PMID- 24307768
TI  - Agonistic approach of omega-3, omega-6 and its metabolites with BDNF: An in
      silico study.
AB  - Brain derived neurotrophic factor (BDNF) is a member of neurotrophic family of
      growth factors, mainly found in the hippocampus and cerebral cortex of brain.
      Studies have shown that there is a link between BDNF and cognitive dysfunction,
      as well as there is a relationship between the PUFAs intake and their effect on
      BDNF production. Intake of PUFAs, mainly omega-3 and omega-6 has show increase in
      production of BDNF in brain. In our study we performed docking studies on PUFAs
      and their metabolites with BDNF using MVD (Molegro Virtual Docker), this has
      shown that the metabolites of the PUFAs mainly LXA_4, NPD1, HDHA have shown more
      binding affinity towards BDNF. These metabolites of PUFAs are responsible for
      modulation of BDNF activity. 

PMID- 24307769
TI  - Comparative Genomics of Trypanosomatid Pathogens using Codon Usage Bias.
AB  - It is well known that an amino acid can be encoded by more than one codon, called
      synonymous codons. The preferential use of one particular codon for coding an
      amino acid is referred to as codon usage bias (CUB). A quantitative analytical
      method, CUB and a related tool, Codon Adaptative Index have been applied to
      comparatively study whole genomes of a few pathogenic Trypanosomatid species.
      This quantitative attempt is of direct help in the comparison of qualitative
      features like mutational and translational selection. Pathogens of the Leishmania
      and Trypanosoma genus cause debilitating disease and suffering in human beings
      and animals. Of these, whole genome sequences are available for only five
      species. The complete coding sequences (CDS), highly expressed, essential and low
      expressed genes have all been studied for their CUB signature. The codon usage
      bias of essential genes and highly expressed genes show distribution similar to
      codon usage bias of all CDSs in Trypanosomatids. Translational selection is the
      dominant force selecting the preferred codon, and selection due to mutation is
      negligible. In contrast to an earlier study done on these pathogens, it is found
      in this work that CUB and CAI may be used to distinguish the Trypanosomatid
      genomes at the sub-genus level. Further, CUB may effectively be used as a
      signature of the species differentiation by using Principal Component Analysis
      (PCA). ABBREVIATIONS: CUB - Codon Usage Bias, CAI - Codon Adaptative Index, CDS -
      Coding sequences, t-RNA - Transfer RNA, PCA - Principal Component Analysis.

PMID- 24307770
TI  - Screening of MicroRNA as potential CardiomiRs in Rattus noveregicus Heart related
      Dataset.
AB  - MicroRNAs (miRNAs) are the naturally expressed small, 18~25 nts long non-coding
      single stranded RNAs, which inhibit the translation by interacting with the 3'
      untranslated region (UTR) of specific mRNA targets or by repression of
      posttranscriptional modification of mRNAs. MiRNAs are found to regulate the
      differentiation, development, function and stress responsive growth of cardiac
      cells. Their role and association with several disease progressions is of
      interest in recent years. Our interest is to study their role in cardiac
      hypertrophy (characterized by increased cell size, protein synthesis and
      reactivation of gene pathways). Therefore, we analyzed their features using a
      dataset (# ~1400 #) of potential intronic and 3'UTR targeted miRNAs from known
      cardiac marker genes. We report 10 uncharacterized miRNAs regulating cardiac
      marker genes during cardiac hypertrophy and other cardiac diseases. 

PMID- 24307771
TI  - Comparative genome analysis of Solanum lycopersicum and Solanum tuberosum.
AB  - Solanum lycopersicum and Solanum tuberosum are agriculturally important crop
      species as they are rich sources of starch, protein, antioxidants, lycopene, beta
      carotene, vitamin C, and fiber. The genomes of S. lycopersicum and S. tuberosum
      are currently available. However the linear strings of nucleotides that together
      comprise a genome sequence are of limited significance by themselves.
      Computational and bioinformatics approaches can be used to exploit the genomes
      for fundamental research for improving their varieties. The comparative genome
      analysis, Pfam analysis of predicted reviewed paralogous proteins was performed.
      It was found that S. lycopersicum proteins belong to more families, domains and
      clans in comparison with S. tuberosum. It was also found that mostly intergenic
      regions are conserved in two genomes followed by exons, intron and UTR. This can
      be exploited to predict regions between genomes that are similar to each other
      and to study the evolutionary relationship between two genomes, leading towards
      the development of disease resistance, stress tolerance and improved varieties of
      tomato. 

PMID- 24307772
TI  - A Structured-based Model for the Decreased Activity of Ala222Val and Glu429Ala
      Methylenetetrahydrofolate Reductase (MTHFR) Mutants.
AB  - The structure of human Methylenetetrahydrofolate Reductase (MTHFR) is not known
      either by NMR or by X-ray methods. Phosphorylation seems to play an important
      role in the functioning of this flavoprotein. MTHFR catalyzes an irreversible
      reaction in homocysteine metabolism. Phosphorylation decreases the activity of
      MTHFR by enhancing the sensitivity of the enzyme to SAdenosylmethione. Two common
      polymorphisms in MTHFR, Ala222Val and Glu429Ala, can result in a number of
      vascular diseases. Effects of the Glu429Ala polymorphism on the structure of
      human MTHFR remain undetermined due to limited structural information. Hence,
      structural models of the MTHFR mutants were constructed using I-TASSER and
      assessed by PROCHECK, DFIRE and Verify3D tools. A mechanism is further suggested
      for the decreased activity of the Ala222Val and Glu429Ala mutants due to a
      decrease in number of serine phosphorylation sites using information gleaned from
      the molecular models. This provides insights for the understanding of structure
      function relationship for MTHFR. 

PMID- 24307773
TI  - DPPrimer - A Degenerate PCR Primer Design Tool.
AB  - Designed degenerate primers unlike conventional primers are superior in matching
      and amplification of large number of genes, from related gene families. DPPrimer
      tool was designed to predict primers for PCR amplification of homologous gene
      from related or diverse plant species. The key features of this tool include
      platform independence and user friendliness in primer design. Embedded features
      such as search for functional domains, similarity score selection and
      phylogebetic tree further enhance the user friendliness of DPPrimer tool.
      Performance of DPPrimer tool was evaluated by successful PCR amplification of ADP
      glucose phosphorylase genes from wheat, barley and rice. AVAILABILITY: DPPrimer
      is freely accessible at http://202.141.12.147/DGEN_tool/index.html.

PMID- 24307774
TI  - DIACAN: Integrated Database for Antidiabetic and Anticancer Medicinal Plants.
AB  - Medicinal plants and plant derived molecules are widely used in traditional
      cultures all over the world and they are becoming large popular among biomedical
      researchers and pharmaceutical companies as a natural alternative to synthetic
      medicine. Information related to medicinal plants and herbal drugs accumulated
      over the ages are scattered and unstructured which make it prudent to develop a
      curated database for medicinal plants. The Antidiabetic and Anticancer Medicinal
      Plants Database (DIACAN) aims to collect and provide an integrated platform for
      plants and phytochemiclas having antidiabetic or anticancer activity.
      AVAILABILITY: http://www.kaubic.in/diacan.

PMID- 24307775
TI  - Is liver biopsy necessary in the management of alcoholic hepatitis?
AB  - Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients
      with a history of heavy alcohol use, which can progress to liver failure. A
      clinical diagnosis of AAH can be challenging to make in patients without a clear
      alcohol history or in the presence of risk factors for other causes of acute
      liver failure. Other causes of acute on chronic liver failure such as sepsis or
      variceal haemorrhage should be considered. Liver biopsy remains the only reliable
      method to make an accurate diagnosis. However, there is controversy surrounding
      the use of liver biopsy in patients with AAH because of the risks of performing a
      percutaneous biopsy and limitations in access to transjugular biopsy. We review
      the existing literature and find there are few studies directly comparing
      clinical and histological diagnosis of AAH. In the small number of studies that
      have been conducted the correlation between a clinical and histological diagnosis
      of AAH is poor. Due to this lack of agreement together with difficulties in
      accessing transjugular liver biopsy outside tertiary referral centres and
      research institutions, we cannot advocate universal biopsy for AAH but there
      remains a definite role for liver biopsy where there is clinical diagnostic doubt
      or dual pathology. It also adds value in a clinical trial context to ensure a
      homogeneous trial population and to further our understanding of the disease
      pathology. Further prospective studies are required to determine whether non
      invasive markers can be used to accurately diagnose AAH. 

PMID- 24307776
TI  - Improvement analysis of article quality in World Journal of Gastroenterology
      during 2008-2012.
AB  - AIM: To understand the changes and development of World Journal of
      Gastroenterology (WJG) in recent years. METHODS: The Journal Citation Report
      (JCR) and SCI-E database of the ISI Web of Knowledge were used to search the
      articles and data of related indices in WJG during 2008-2012. Bibliometric
      methods were used for statistical analysis of the author's degree of
      collaboration, collaboration rate, the first author's publications, high
      productivity authors, the authors' origins in each year; the distribution of the
      countries and journals of the authors citing WJG papers was also analyzed. In
      addition, the indices related to this journal in each year were compared with the
      data from 6 SCI journals in the field of gastroenterology in the 2012 volume.
      RESULTS: A total of 4409 papers in WJG were examined in this study. For the
      period 2008-2012, the self-citation rate was 8.59%, 6.02%, 5.50%, 4.47% and
      5.21%. Of a total of 3898 first authors, 3526 published 1 paper, 291 published 2
      papers, 59 published 3 papers, and 22 published 4 or more papers. The origin of
      WJG authors covered the six continents, and the majority came from Asia, Europe
      and North America. The number of countries of origin of WJG authors was 65, 66,
      61, 65 an 60 for the period 2008-2012. Authors from 66 countries cited a total of
      3194 of the 4409 papers, and these citations were found in 1140 journals.
      CONCLUSION: The results suggest that WJG has stayed on the track of normal
      international publication and all the indices of this journal are stable and
      reasonable.

PMID- 24307777
TI  - Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma: dysregulation
      and implications for early detection, diagnosis and therapy.
AB  - Hepatitis C virus (HCV) infection is one of main causes of hepatocellular
      carcinoma (HCC) and the prevalence of HCV-associated HCC is on the rise
      worldwide. It is particularly important and helpful to identify potential markers
      for screening and early diagnosis of HCC among high-risk individuals with chronic
      hepatitis C, and to identify target molecules for the prevention and treatment of
      HCV-associated-HCC. Small non-coding RNAs, mainly microRNAs (miRNAs), and long
      non-coding RNAs (lncRNAs) with size greater than 200 nucleotides, are likely to
      play important roles in a variety of biological processes, including development
      and progression of HCC. For the most part their underlying mechanisms of action
      remain largely unknown. In recent years, with the advance of high-resolution of
      microarray and application of next generation sequencing techniques, a
      significant number of non-coding RNAs (ncRNAs) associated with HCC, particularly
      caused by HCV infection, have been found to be differentially expressed and to be
      involved in pathogenesis of HCV-associated HCC. In this review, we focus on
      recent studies of ncRNAs, especially miRNAs and lncRNAs related to HCV-induced
      HCC. We summarize those ncRNAs aberrantly expressed in HCV-associated HCC and
      highlight the potential uses of ncRNAs in early detection, diagnosis and therapy
      of HCV-associated HCC. We also discuss the limitations of recent studies, and
      suggest future directions for research in the field. miRNAs, lncRNAs and their
      target genes may represent new candidate molecules for the prevention, diagnosis
      and treatment of HCC in patients with HCV infection. Studies of the potential
      uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their
      infancy. 

PMID- 24307778
TI  - Hepatitis C virus control among persons who inject drugs requires overcoming
      barriers to care.
AB  - Despite a high prevalence of hepatitis C virus (HCV) infection, the vast majority
      of persons who inject drugs (PWID) have not engaged in HCV care due to a large
      number of obstacles. Education about the infection among both PWID and providers
      remains an important challenge as does discrimination faced by PWID in
      conventional health care settings. Many providers also remain hesitant to
      prescribe antiviral therapy due to concerns about adherence and relapse to drug
      use resulting in reinfection. Presently, however, as a result of improvements in
      treatment efficacy combined with professional society and government endorsement
      of HCV treatment for PWID, a pressing need exists to develop strategies to engage
      these individuals into HCV care. In this article, we propose several strategies
      that can be pursued in an attempt to engage PWID into HCV management. We advocate
      that multidisciplinary approaches that utilize health care practitioners from a
      wide range of specialties, as well as co-localization of medical services, are
      strategies likely to result in increased numbers of PWID entering into HCV
      management. Pursuit of HCV therapy after stabilization through drug treatment is
      an additional strategy likely to increase PWID engagement into HCV care. The full
      impact of direct acting antivirals for HCV will only be realized if innovative
      approaches are pursued to engage all HCV infected individuals into treatment. 

PMID- 24307780
TI  - Tumor necrosis factor-alpha inhibitors and chronic hepatitis C: a comprehensive
      literature review.
AB  - Tumor necrosis factor-alpha (TNF-alpha) inhibitors are known to increase
      reactivation of concurrent chronic hepatitis B, but their impact on the hepatitis
      C virus (HCV) is controversial. Some conditions of immunosuppression, such as
      liver transplantation, typically cause an increase in the rate of HCV evolution.
      Inhibition of TNF-alpha, a cytokine involved in the apoptotic signaling pathway
      of hepatocytes infected by HCV, could potentially increase viral replication.
      Currently available clinical data appear to contradict this hypothesis. A review
      of medical literature revealed that a total of 216 patients with HCV were exposed
      to one or more treatments with TNF-alpha inhibitors, with a median observation
      time of 1.2 years and 260 cumulative patient-years of exposure. Only three cases
      of drug withdrawal due to suspected HCV liver disease recrudescence were
      reported. Treatment with TNF-alpha inhibitors in patients with HCV infection
      appears to be safe in the short term, but there are insufficient data to assess
      their long-term safety. Universal screening for HCV before beginning treatment
      with TNF-alpha inhibitors is currently controversial. The presence of HCV is not
      a contraindication to therapy with TNF-alpha inhibitors, with the exception of
      cirrhotic patients. In cases of cirrhosis, the benefit/risk ratio should be
      evaluated at the individual level. Prior to treatment with TNF-alpha inhibitors,
      patients with HCV should be referred to a hepatologist to determine the necessity
      of hepatic disease assessment, using liver biopsy or non-invasive methods, and
      the potential indication for antiviral therapy. In patients with HCV infection
      who are treated with TNF-alpha inhibitors, liver function monitoring every three
      months is advised. 

PMID- 24307781
TI  - Relationships between lymphomas linked to hepatitis C virus infection and their
      microenvironment.
AB  - The relationships between lymphomas and their microenvironment appear to follow 3
      major patterns: (1) an independent pattern; (2) a dependent pattern on
      deregulated interactions; and (3) a dependent pattern on regulated coexistence.
      Typical examples of the third pattern are hepatitis C virus (HCV)-associated
      marginal zone lymphomas (MZLs) and mucosa-associated lymphoid tissue lymphomas.
      In these lymphomas, a regulated coexistence of the malignant cells and the
      microenvironmental factors usually occurs. At least initially, however, tumor
      development and cell growth largely depend on external signals from the
      microenvironment, such as viral antigens, cytokines, and cell-cell interactions.
      The association between HCV infection and B-cell lymphomas is not completely
      defined, although this association has been demonstrated by epidemiological
      studies. MZL and diffuse large B-cell lymphoma are the histotypes most frequently
      associated with HCV infection. Many mechanisms have been proposed for explaining
      HCV-induced lymphomagenesis; antigenic stimulation by HCV seems to be fundamental
      in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B
      cell lymphomas. Recently, antiviral treatment has been proved to be effective in
      the treatment of HCV-associated indolent lymphomas. Importantly, clinically
      responses were linked to the eradication of the HCV-RNA, providing a strong
      argument in favor of a causative link between HCV and lymphoproliferation. 

PMID- 24307779
TI  - Between Scylla and Charybdis: the role of the human immune system in the
      pathogenesis of hepatitis C.
AB  - Hepatitis C virus (HCV) frequently elicits only mild immune responses so that it
      can often establish chronic infection. In this case HCV antigens persist and
      continue to stimulate the immune system. Antigen persistence then leads to
      profound changes in the infected host's immune responsiveness, and eventually
      contributes to the pathology of chronic hepatitis. This topic highlight
      summarizes changes associated with chronic hepatitis C concerning innate immunity
      (interferons, natural killer cells), adaptive immune responses (immunoglobulins,
      T cells, and mechanisms of immune regulation (regulatory T cells). Our overview
      clarifies that a strong anti-HCV immune response is frequently associated with
      acute severe tissue damage. In chronic hepatitis C, however, the effector arms of
      the immune system either become refractory to activation or take over regulatory
      functions. Taken together these changes in immunity may lead to persistent liver
      damage and cirrhosis. Consequently, effector arms of the immune system will not
      only be considered with respect to antiviral defence but also as pivotal
      mechanisms of inflammation, necrosis and progression to cirrhosis. Thus, avoiding
      Scylla - a strong, sustained antiviral immune response with inital tissue damage 
      takes the infected host to virus-triggered immunopathology, which ultimately
      leads to cirrhosis and liver cancer - the realm of Charybdis. 

PMID- 24307782
TI  - Burden of pediatric hepatitis C.
AB  - Hepatitis C virus (HCV) is a major health burden infecting 170-210 million people
      worldwide. Additional 3-4 millions are newly-infected annually. Prevalence of
      pediatric infection varies from 0.05%-0.36% in the United States and Europe; up
      to 1.8%-5.8% in some developing countries. The highest prevalence occurs in
      Egypt, sub-Saharan Africa, Amazon basin and Mongolia. HCV has been present in
      some populations for several centuries, notably genotypes 1 and 2 in West Africa.
      Parenteral anti-schistosomal therapy practiced in the 1960s until the early 1980s
      had spread HCV infection throughout Egypt. Parenteral acquisition of HCV remains
      a major route for infection among Egyptian children. Insufficient screening of
      transfusions, unsterilized injection equipment and re-used needles and syringes
      continue to be major routes of HCV transmission in developing countries, whereas
      vertical transmission and adolescent high-risk behaviors (e.g., injection drug
      abuse) are the major routes in developed countries. The risk of vertical
      transmission from an infected mother to her unborn/newborn infant is
      approximately 5%. Early stages of HCV infection in children do not lead to marked
      impairment in the quality of life nor to cognitive, behavioral or emotional
      dysfunction; however, caregiver stress and family system strain may occur. HCV
      slowly progresses to serious complications as cirrhosis (1%-2%) and
      hepatocellular carcinoma (HCC) especially in the presence of risk factors as
      hemolytic anemias, obesity, treated malignancy, and concomitant human immune
      deficiency and/or hepatitis B virus co-infection. HCV vaccine remains elusive to
      date. Understanding the immune mechanisms in patients who successfully cleared
      the infection is essential for vaccine development. The pediatric standard of
      care treatment consists of pegylated interferon-alpha 2a or b plus ribavirin for
      24-48 wk. The new oral direct acting antivirals, approved for adults, need
      further evaluation in children. Sustained virologic response varies depending on
      the viral load, genotype, duration of infection, degree of aminotransferase
      elevation, adiposity and single nucleotide polymorphisms of interleukin (IL)-28B
      locus. The goals of treatment in individual patients are virus eradication,
      prevention of cirrhosis and HCC, and removing stigmatization; meanwhile the
      overall goal is decreasing the global burden of HCV. IL-28B polymorphisms have
      been also associated with spontaneous clearance of vertically acquired HCV
      infection. The worldwide economic burden of HCV for children, families and
      countries is estimated to be hundreds of millions of US dollars per year. The
      United States, alone, is estimated to spend 199-336 million dollars in screening,
      monitoring and treatment during one decade. The emotional burden of having an HCV
      infected child in a family is more difficult to estimate. 

PMID- 24307783
TI  - Direct effects of hepatitis C virus on the lymphoid cells.
AB  - It has been reported that the direct binding of hepatitis C virus (HCV) and/or
      the replication of HCV in the extrahepatic organs and, especially, lymphoid
      cells, might affect the pathogenesis of extrahepatic diseases with HCV infection.
      More than one decade ago, several reports described the existence of HCV-RNA in
      peripheral blood mononuclear cells. Moreover, many reports describing the
      existence of HCV in B lymphocytes and B cell lymphoma have been published. In
      addition to B lymphocytes, it was reported that HCV replication could be detected
      in T lymphocytes and T cell lines. Among the extrahepatic diseases with HCV
      infection, mixed cryoglobulinemia-related diseases and autoimmune-related
      diseases are important for understanding the immunopathogensis of HCV persistent
      infection. Moreover, HCV persistent infection can cause malignant lymphoma. The
      biological significance of lymphotropic HCV has not yet become clear. However,
      several candidates have been considered for a long time. One is that lymphotropic
      HCV is an HCV reservoir that might contribute to the recurrence of HCV infection
      and difficult-to-treat disease status. The other important issue is the
      carcinogenesis of the lymphoid cells and disturbances of the immune responses.
      Therefore, the extrahepatic diseases might be induced by direct interaction
      between HCV and lymphoid cells. In this article, we summarize various studies
      showing the direct effect of HCV on lymphoid cells and discuss the biological
      significance of lymphotropic HCV. 

PMID- 24307784
TI  - An insight into the diagnosis and pathogenesis of hepatitis C virus infection.
AB  - This review focuses on research findings in the area of diagnosis and
      pathogenesis of hepatitis C virus (HCV) infection over the last few decades. The
      information based on published literature provides an update on these two aspects
      of HCV. HCV infection, previously called blood transmitted non-A, non-B
      infection, is prevalent globally and poses a serious public health problem
      worldwide. The diagnosis of HCV infection has evolved from serodetection of non
      specific and low avidity anti-HCV antibodies to detection of viral nucleic acid
      in serum using the polymerase chain reaction (PCR) technique. Current PCR assays
      detect viral nucleic acid with high accuracy and the exact copy number of viral
      particles. Moreover, multiplex assays using real-time PCR are available for
      identification of HCV-genotypes and their isotypes. In contrast to previous
      methods, the newly developed assays are not only fast and economic, but also
      resolve the problem of the window period as well as differentiate present from
      past infection. HCV is a non-cytopathic virus, thus, its pathogenesis is
      regulated by host immunity and metabolic changes including oxidative stress,
      insulin resistance and hepatic steatosis. Both innate and adaptive immunity play
      an important role in HCV pathogenesis. Cytotoxic lymphocytes demonstrate crucial
      activity during viral eradication or viral persistence and are influenced by
      viral proteins, HCV-quasispecies and several metabolic factors regulating liver
      metabolism. HCV pathogenesis is a very complex phenomenon and requires further
      study to determine the other factors involved. 

PMID- 24307786
TI  - Liver function impairment in liver transplantation and after extended
      hepatectomy.
AB  - Extended hepatectomy, or liver transplantation of reduced-size graft, can lead to
      a pattern of clinical manifestations, namely "post-hepatectomy liver failure" and
      "small-for-size syndrome" respectively, that can range from mild cholestasis to
      irreversible organ non-function and death of the patient. Many mechanisms are
      involved in their occurrence but in the recent past, high portal blood flow
      through a relatively small liver vascular bed has taken a central role.
      Therefore, several techniques of inflow modulation have been attempted in cases
      of portal hyperperfusion first in liver transplantation, such as portocaval
      shunt, mesocaval shunt, splenorenal shunt, splenectomy or ligation of the splenic
      artery. However, high portal flow is not the only factor responsible, and before
      major liver resections, preoperative assessment of the residual liver function is
      necessary. Techniques such as portal vein embolization or portal vein ligation
      can be adopted to increase the future liver volume, preventing post-hepatectomy
      liver failure. More recently, a new surgical procedure, that combines in situ
      splitting of the liver and portal vein ligation, has gradually come to light,
      inducing remarkable hypertrophy of the healthy liver in just a few days. Further
      studies are needed to confirm this hypothesis and overcome one of the biggest
      issues in the field of liver surgery. 

PMID- 24307785
TI  - Scotomas in molecular virology and epidemiology of hepatitis C virus.
AB  - In the 1970s, scientists learned of a new pathogen causing non-A, non-B
      hepatitis. Classical approaches were used to isolate and characterize this new
      pathogen, but it could be transmitted experimentally only to chimpanzees and
      progress was slow until the pathogen was identified as hepatitis C virus (HCV) in
      1989. Since then, research and treatment of HCV have expanded with the
      development of modern biological medicine: HCV genome organization and
      polyprotein processing were delineated in 1993; the first three-dimensional
      structure of HCV nonstructural protein (NS3 serine protease) was revealed in
      1996; an infectious clone of HCV complementary DNA was first constructed in 1997;
      interferon and ribavirin combination therapy was established in 1998 and the
      therapeutic strategy gradually optimized; the HCV replicon system was produced in
      1999; functional HCV pseudotyped viral particles were described in 2003; and
      recombinant infectious HCV in tissue culture was produced successfully in 2005.
      Recently, tremendous advances in HCV receptor discovery, understanding the HCV
      lifecycle, decryption of the HCV genome and proteins, as well as new anti-HCV
      compounds have been reported. Because HCV is difficult to isolate and culture,
      researchers have had to avail themselves to the best of modern biomedical
      technology; some of the major achievements in HCV research have not only advanced
      the understanding of HCV but also promoted knowledge of virology and cellular
      physiology. In this review, we summarize the advancements and remaining scotomas
      in the molecular virology and epidemiology of HCV. 

PMID- 24307787
TI  - Exocrine pancreatic insufficiency in adults: a shared position statement of the
      Italian Association for the Study of the Pancreas.
AB  - This is a medical position statement developed by the Exocrine Pancreatic
      Insufficiency collaborative group which is a part of the Italian Association for
      the Study of the Pancreas (AISP). We covered the main diseases associated with
      exocrine pancreatic insufficiency (EPI) which are of common interest to
      internists/gastroenterologists, oncologists and surgeons, fully aware that EPI
      may also occur together with many other diseases, but less frequently. A
      preliminary manuscript based on an extended literature search (Medline/PubMed,
      Cochrane Library and Google Scholar) of published reports was prepared, and key
      recommendations were proposed. The evidence was discussed at a dedicated meeting
      in Bologna during the National Meeting of the Association in October 2012. Each
      of the proposed recommendations and algorithms was discussed and an initial
      consensus was reached. The final draft of the manuscript was then sent to the
      AISP Council for approval and/or modification. All concerned parties approved the
      final version of the manuscript in June 2013. 

PMID- 24307788
TI  - MicroRNAs as tools to predict glucocorticoid response in inflammatory bowel
      diseases.
AB  - In spite of the introduction in therapy of highly effective biological agents,
      glucocorticoids (GCs) are still employed to induce remission in moderate to
      severe inflammatory bowel diseases (IBD), but considerable inter-individual
      differences in their efficacy and side effects have been reported. The
      effectiveness of these drugs is indeed very variable and side effects,
      particularly severe in pediatric patients, are common and often unpredictable:
      the understanding of the complex gene regulation mediated by GCs could shed light
      on the causes of this variability. In this context, microRNAs (miRNAs) represent
      a new and promising field of research. miRNAs are small non-coding RNA molecules
      that suppress gene expression at post-transcriptional level, and are fine-tuning
      regulators of diverse biological processes, including the development and
      function of the immune system, apoptosis, metabolism and inflammation. Emerging
      data have implicated the deregulated expression of certain miRNA networks in the
      pathogenesis of autoimmune and inflammatory diseases, such as IBD. There is a
      great interest in the identification of the role of miRNAs in the modulation of
      pharmacological response; however, the association between miRNA and GC response
      in patients with IBD has not yet been evaluated in a prospective clinical study.
      The identification of miRNAs differently expressed as a consequence of GC
      treatment in comparison to diagnosis, represents an important innovative approach
      that could be translated into clinical practice. In this review we highlight the
      altered regulation of proteins involved in GC molecular mechanism by miRNAs, and
      their potential role as molecular markers useful for predicting in advance GC
      response. 

PMID- 24307789
TI  - Anti-angiogenic therapies for metastatic colorectal cancer: current and future
      perspectives.
AB  - Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the
      second leading cause of cancer death in both men and women in the United States,
      with about 142820 new cases and 50830 deaths expected in 2013. Metastatic disease
      (mCRC) remains a challenge for oncologists worldwide due to its potential
      comorbidities. Recently, chemotherapy regimens containing 5-fluorouracil,
      leucovorin, oxaliplatin and irinotecan combinations are a standard of care in the
      metastatic disease. Currently, biological therapies involving vascular
      endothelial growth factor and epidermal growth factor receptor pathways, such as
      bevacizumab and cetuximab, have emerged as good option for improving mCRC patient
      survival. Now, aflibercept plus standard chemotherapy has also been approved in
      second line regimen for mCRC patients. Our review will discuss novel biological
      drugs and their indications for mCRC patients and will bring future perspectives
      in this regard. 

PMID- 24307790
TI  - Alcoholism and liver disease in Mexico: genetic and environmental factors.
AB  - Alcoholism and cirrhosis, which are two of the most serious health problems
      worldwide, have a broad spectrum of clinical outcomes. Both diseases are
      influenced by genetic susceptibility and cultural traits that differ globally but
      are specific for each population. In contrast to other regions around the world,
      Mexicans present the highest drinking score and a high mortality rate for
      alcoholic liver disease with an intermediate category level of per capita alcohol
      consumption. Mexico has a unique history of alcohol consumption that is linked to
      profound anthropological and social aspects. The Mexican population has an
      admixture genome inherited from different races, Caucasian, Amerindian and
      African, with a heterogeneous distribution within the country. Thus, genes
      related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver
      alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide
      B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one
      individual to another. Furthermore, they may be inherited as risk or non-risk
      haplogroups that confer susceptibility or resistance either to alcohol addiction
      or abusive alcohol consumption and possibly liver disease. Thus, in this era of
      genomics, personalized medicine will benefit patients if it is directed according
      to individual or population-based data. Additional association studies will be
      required to establish novel strategies for the prevention, care and treatment of
      liver disease in Mexico and worldwide.

PMID- 24307792
TI  - Splanchnic-aortic inflammatory axis in experimental portal hypertension.
AB  - Splanchnic and systemic low-grade inflammation has been proposed to be a
      consequence of long-term prehepatic portal hypertension. This experimental model
      causes minimal alternations in the liver, thus making a more selective study
      possible for the pathological changes characteristic of prehepatic portal
      hypertension. Low-grade splanchnic inflammation after long-term triple partial
      portal vein ligation could be associated with liver steatosis and portal
      hypertensive intestinal vasculopathy. In fact, we have previously shown that
      prehepatic portal hypertension in the rat induces liver steatosis and changes in
      lipid and carbohydrate metabolism similar to those produced in chronic
      inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and
      bacterial translocation in this experimental model suggest the existence of a
      portal hypertensive intestinal microbiome implicated in both the splanchnic and
      systemic alterations related to prehepatic portal hypertension. Among the
      systemic impairments, aortopathy characterized by oxidative stress, increased
      levels of proinflammatory cytokines and profibrogenic mediators stand out. In
      this experimental model of long-term triple portal vein ligated-rats, the
      abdominal aortic proinflammatory response could be attributed to oxidative
      stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide
      phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen
      species production and promote aortic inflammation. Also, oxidative stress
      mediated by NAD(P)H oxidase has been associated with risk factors for
      inflammation and atherosclerosis. The splanchnic and systemic pathology that is
      produced in the long term after triple partial portal vein ligation in the rat
      reinforces the validity of this experimental model to study the chronic low-grade
      inflammatory response induced by prehepatic portal hypertension. 

PMID- 24307791
TI  - Management of post-hepatectomy complications.
AB  - Hepatic resection had an impressive growth over time. It has been widely
      performed for the treatment of various liver diseases, such as malignant tumors,
      benign tumors, calculi in the intrahepatic ducts, hydatid disease, and abscesses.
      Management of hepatic resection is challenging. Despite technical advances and
      high experience of liver resection of specialized centers, it is still burdened
      by relatively high rates of postoperative morbidity and mortality. Especially,
      complex resections are being increasingly performed in high risk and older
      patient population. Operation on the liver is especially challenging because of
      its unique anatomic architecture and because of its vital functions. Common post
      hepatectomy complications include venous catheter-related infection, pleural
      effusion, incisional infection, pulmonary atelectasis or infection, ascites,
      subphrenic infection, urinary tract infection, intraperitoneal hemorrhage,
      gastrointestinal tract bleeding, biliary tract hemorrhage, coagulation disorders,
      bile leakage, and liver failure. These problems are closely related to surgical
      manipulations, anesthesia, preoperative evaluation and preparation, and
      postoperative observation and management. The safety profile of hepatectomy
      probably can be improved if the surgeons and medical staff involved have
      comprehensive knowledge of the expected complications and expertise in their
      management. This review article focuses on the major postoperative issues after
      hepatic resection and presents the current management. 

PMID- 24307793
TI  - Identification and characterization of a novel bipartite nuclear localization
      signal in the hepatitis B virus polymerase.
AB  - AIM: To characterize the nuclear import of hepatitis B virus (HBV) polymerase (P)
      and its relevance for the viral life cycle. METHODS: Sequence analysis was
      performed to predict functional motives within P. Phosphorylation of P was
      analyzed by in vitro phosphorylation. Phosphorylation site and nuclear
      localization signal (NLS) were destroyed by site directed mutagenesis.
      Functionality of the identified NLS was analyzed by confocal fluorescence
      microscopy and characterizing the karyopherin binding. Relevance of the
      structural motives for viral life cycle was studied by infection of primary
      Tupaia hepatocytes with HBV. RESULTS: We identified by sequence alignment and
      functional experiments a conserved bipartite NLS containing a casein kinase II
      (CKII) phosphorylation site located within the terminal protein domain (TP) of
      the HBV polymerase. Inhibition of CKII impairs the functionality of this NLS and
      thereby prevents the nuclear import of the polymerase. Binding of the import
      factor karyopherin-alpha2 to the polymerase depends on its CKII-mediated
      phosphorylation of the bipartite NLS. In HBV-infected primary Tupaia hepatocytes
      CKII inhibition in the early phase (post entry phase) of the infection process
      prevents the establishment of the infection. CONCLUSION: Based on these data it
      is suggested that during HBV infection the final import of the genome complex
      into the nucleus is mediated by a novel bipartite NLS localized in the TP domain
      of HBV polymerase.

PMID- 24307794
TI  - Addicts with chronic hepatitis C: difficult to reach, manage or treat?
AB  - AIM: To assess the acceptance, safety and efficacy of care and treatment for
      chronic hepatitis C (CHC) in drug addicts. METHODS: We designed a
      multidisciplinary, phase IV prospective cohort study. All illicit drug users
      (IDUs) visited a Territorial Addiction Service (SerT) in the District of Brescia,
      and hepatitis C antibody (HCVAb) testing positive were offered as part of a
      standardised hepatologic visit in our Gastroenterology Unit. Patients with
      confirmed CHC and without medical contraindications were administered
      peginterferon alfa-2b 1.5 MUg/kg per week plus ribavirin (800-1400 mg/d) for 16
      48 wk. All IDUs were unselected because of ongoing addiction and read and signed
      an informed consent form. Virologic responses at weeks 4 and 12 of therapy, at
      the end of treatment and 24 wk after the end of treatment were the main measures
      of efficacy. Adherence was estimated according to the 80/80/80 criteria. RESULTS:
      From November 2007 to December 2009, 162 HCVAb+ IDUs were identified. Sixty-seven
      patients (41% of the initial cohort) completed the diagnostic procedure, and CHC
      was diagnosed in 54 (33% of the total). Forty-nine patients were offered therapy,
      and 39 agreed (80% of acceptance rate). The prevalent HCV genotype was type 1,
      and the HCV RNA baseline level was over 5.6 log/mL in 61% of cases. Five patients
      dropped out, two because of severe adverse events (SAEs) and three without
      medical need. Twenty-three and 14 patients achieved end of treatment responses
      (ETRs; 59%) and sustained virologic responses (SVRs; 36%), respectively. Thirty
      one patients were fully compliant with the study protocol (80% adherence). The
      prevalence of host and viral characteristics negatively affecting the treatment
      response was high: age over 40 years (54%), male gender (85%), overweight body
      type (36%), previous unsuccessful antiviral therapy (21%), HCV genotype and viral
      load (60% and 62%, respectively), earlier contact with HBV (40%) and steatosis
      and fibrosis (44% and 17%, respectively). In a univariate analysis, alcohol
      intake was associated with a non-response (P = 0.0018, 95%CI: 0.0058-0.4565).
      CONCLUSION: Drug addicts with CHC can be successfully treated in a
      multidisciplinary setting using standard antiviral combination therapy, despite
      several "difficult to reach, manage and treat" characteristics.

PMID- 24307795
TI  - Expression of hepatitis B virus 1.3-fold genome plasmid in an SV40 T-antigen
      immortalized mouse hepatic cell line.
AB  - AIM: To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome
      plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T
      antigen (SV40T) expression. METHODS: Mouse hepatic cells were isolated from mouse
      liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase
      digestion method and cultured in vitro. The pRSV-T plasmid was transfected into
      mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line.
      The SV40LT-immortalized mouse hepatic cells were identified and transfected with
      the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and
      hepatitis B e antigen (HBeAg) in the supernatant were determined by an
      electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection.
      The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were
      investigated by indirect immunofluorescence analysis. The presence of HBV DNA
      replication intermediates in the transfected cells and viral particles in the
      supernatant of the transfected cell cultures was monitored using the Southern
      hybridization assay and transmission electronic microscopy, respectively.
      RESULTS: The pRSV-T plasmid was used to immortalize mouse hepatocytes and an
      SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT
      immortalized mouse hepatic cells have the same morphology and growth
      characteristics as primary mouse hepatic cells can be subcultured and produce
      albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not
      show the characteristics of tumor cells, as alpha-fetoprotein levels were
      comparable (0.58 +/- 0.37 vs 0.61 +/- 0.31, P = 0.37). SV40LT-immortalized mouse
      hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found
      that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The
      levels of HBsAg and HBeAg continuously increased in the supernatant after the
      transfection of pHBV1.3, and began to decrease 72 h after transfection. The
      expressions of HBsAg and HBcAg were observed in the pHBV1.3-transfected cells.
      HBV DNA replication intermediates were also observed at 72 h after transfection,
      including relaxed circular DNA, double-stranded DNA and single-stranded DNA.
      Furthermore, a few 42 nm Dane particles, as well as many 22 nm subviral particles
      with a spherical or filamentous shape, were detected in the supernatant.
      CONCLUSION: SV40T expression can immortalize mouse hepatic cells, and the pHBV1.3
      transfected SV40T-immortalized mouse hepatic cell line can be a new in vitro cell
      model.

PMID- 24307796
TI  - Evaluation of 4 three-dimensional representation algorithms in capsule endoscopy
      images.
AB  - AIM: To evaluate the three-dimensional (3-D) representation performance of 4
      publicly available Shape-from-Shading (SfS) algorithms in small-bowel capsule
      endoscopy (SBCE). METHODS: SfS techniques recover the shape of objects using the
      gradual variation of shading. There are 4 publicly available SfS algorithms. To
      the best of our knowledge, no comparative study with images obtained during
      clinical SBCE has been performed to date. Three experienced reviewers were asked
      to evaluate 54 two-dimensional (2-D) images (categories:
      protrusion/inflammation/vascular) transformed to 3-D by the aforementioned SfS 3
      D algorithms. The best algorithm was selected and inter-rater agreement was
      calculated. RESULTS: Four publicly available SfS algorithms were compared. Tsai's
      SfS algorithm outperformed the rest (selected as best performing in 45/54 SBCE
      images), followed by Ciuti's algorithm (best performing in 7/54 images) and
      Torreao's (in 1/54 images). In 26/54 images; Tsai's algorithm was unanimously
      selected as the best performing 3-D representation SfS software. Tsai's 3-D
      algorithm superiority was independent of lesion category
      (protrusion/inflammatory/vascular; P = 0.678) and/or CE system used to obtain the
      2-D images (MiroCam/PillCam; P = 0.558). Lastly, the inter-observer agreement was
      good (kappa = 0.55). CONCLUSION: 3-D representation software offers a plausible
      alternative for 3-D representation of conventional capsule endoscopy images
      (until optics technology matures enough to allow hardware enabled-"real" 3-D
      reconstruction of the gastrointestinal tract).

PMID- 24307797
TI  - Predictors of Clostridium difficile infection severity in patients hospitalised
      in medical intensive care.
AB  - AIM: To describe and analyse factors associated with Clostridium difficile
      infection (CDI) severity in hospitalised medical intensive care unit patients.
      METHODS: We performed a retrospective cohort study of 40 patients with CDI in a
      medical intensive care unit (MICU) at a French university hospital. We include
      patients hospitalised between January 1, 2007 and December 31, 2011. Data on
      demographics characteristics, past medical history, CDI description was
      collected. Exposure to risk factors associated with CDI within 8 wk before CDI
      was recorded, including previous hospitalisation, nursing home residency,
      antibiotics, antisecretory drugs, and surgical procedures. RESULTS: All included
      cases had their first episode of CDI. The mean incidence rate was 12.94
      cases/1000 admitted patients, and 14.93, 8.52, 13.24, 19.70, and 8.31
      respectively per 1000 admitted patients annually from 2007 to 2011. Median age
      was 62.9 [interquartile range (IQR) 55.4-72.40] years, and 13 (32.5%) were women.
      Median length of MICU stay was 14.0 d (IQR 5.0-22.8). In addition to diarrhoea,
      the clinical symptoms of CDI were fever (> 38  degrees C) in 23 patients,
      abdominal pain in 15 patients, and ileus in 1 patient. The duration of diarrhoea
      was 13.0 (8.0-19.5) d. In addition to diarrhoea, the clinical symptoms of CDI
      were fever (> 38  degrees C) in 23 patients, abdominal pain in 15 patients, and
      ileus in 1 patient. Prior to CDI, 38 patients (95.0%) were exposed to
      antibiotics, and 12 (30%) received at least 4 antibiotics. Fluoroquinolones,
      3(rd) generation cephalosporins, coamoxiclav and tazocillin were prescribed most
      frequently (65%, 55%, 40% and 37.5%, respectively). The majority of cases were
      hospital-acquired (n = 36, 90%), with 5 cases (13.9%) being MICU-acquired.
      Fifteen patients had severe CDI. The crude mortality rate within 30 d after
      diagnosis was 40% (n = 16), with 9 deaths (9 over 16; 56.3%) related to CDI. Of
      our 40 patients, 15 (37.5%) had severe CDI. Multivariate logistic regression
      showed that male gender [odds ratio (OR): 8.45; 95%CI: 1.06-67.16, P = 0.044],
      rising serum C-reactive protein levels (OR = 1.11; 95%CI: 1.02-1.21, P = 0.021),
      and previous exposure to fluoroquinolones (OR = 9.29; 95%CI: 1.16-74.284, P =
      0.036) were independently associated with severe CDI. CONCLUSION: We report
      predictors of severe CDI not dependent on time of assessment. Such factors could
      help in the development of a quantitative score in ICU's patients.

PMID- 24307798
TI  - Prognosis and follow-up of 135 patients with ischemic colitis over a five-year
      period.
AB  - AIM: To study the prognosis (recurrence and mortality) of patients with ischemic
      colitis (IC). METHODS: This study was conducted in four Spanish hospitals,
      participants in the Ischemic Colitis in Spain study We analyzed prospectively 135
      consecutive patients who met criteria for definitive or probable IC according to
      Brandt criteria, and follow up these patients during the next five years,
      retrospectively. Long-term results (recurrence and mortality) were evaluated
      retrospectively after a median interval of 62 mo (range 54-75 mo). RESULTS:
      Estimated IC recurrence rates were 2.9%, 5.1%, 8.1% and 9.7% at years 1, 2, 3 and
      5 years, respectively. Five-year survival was 69% (93 of 135) and 24% (10 of 42
      patients) died for causes related to the IC. Among these 10 patients, 8 died in
      their first episode at hospital (4 had gangrenous colitis and 4 fulminant
      colitis) and 2 due to recurrence. CONCLUSION: The five-year recurrence rate of IC
      was low. On the other hand, mortality during follow-up was high and was not
      associated with ischemic colitis.

PMID- 24307799
TI  - Single balloon enteroscopy for endoscopic retrograde cholangiography in patients
      with Roux-en-Y hepaticojejuno anastomosis.
AB  - AIM: To evaluate single balloon enteroscopy in diagnostic and therapeutic
      endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y
      hepaticojejunoanastomosis (HJA). METHODS: The study took place from January 2009
      to December 2011 and we retrospectively assessed 15 patients with Roux-en-Y HJA
      who had signs of biliary obstruction. In total, 23 ERC procedures were performed
      in these patients and a single balloon videoenteroscope (Olympus SIF Q 180) was
      used in all of the cases. A transparent overtube was drawn over the
      videoenteroscope and it freely moved on the working part of the enteroscope. Its
      distal end was equipped with a silicone balloon that was inflated by air from an
      external pump at a pressure of <= 5.4 kPa. The technical limitations or rather
      the parameters of the single balloon enteroscope (working length - 200 cm,
      diameter of the working channel - 2.8 mm, absence of Albarran bridge) showed the
      need for special endoscopic instrumentation. RESULTS: Cannulation success was
      reached in diagnostic ERC in 12 of 15 patients. ERC findings were normal in 1 of
      12 patients. ERC in the remaining 11 patients showed some pathological changes.
      One of these (cystic bile duct dilation) was subsequently resolved surgically.
      Endoscopic treatment was initialized in the remaining 10 patients (5 with HJA
      stenosis, 2 with choledocholithiasis, and 3 with both). This treatment was
      successful in 9 of 10 patients. The endoscopic therapeutic procedures included:
      balloon dilatation of HJA stenosis - 11 times (7 patients); choledocholitiasis
      extraction - five times (5 patients); biliary plastic stent placement - six times
      (4 patients); and removal of biliary stents placed by us - six times (4
      patients). The mean time of performing a single ERC was 72 min. The longest
      procedure took 110 min and the shortest took 34 min. This shows that it is
      necessary to allow for more time in individual procedures. Furthermore, these
      procedures require the presence of an anesthesiologist. We did not observe any
      complications in these 15 patients. CONCLUSION: This method is more demanding
      than standard endoscopic retrograde cholangiopancreatography due to altered
      postsurgical anatomy. However, it is effective, safe, and widens the
      possibilities of resolving biliary pathology.

PMID- 24307800
TI  - Simultaneous follow-up of mouse colon lesions by colonoscopy and endoluminal
      ultrasound biomicroscopy.
AB  - AIM: To evaluate the potential use of colonoscopy and endoluminal ultrasonic
      biomicroscopy (eUBM) to track the progression of mouse colonic lesions. METHODS:
      Ten mice were treated with a single azoxymethane intraperitoneal injection (week
      1) followed by seven days of a dextran sulfate sodium treatment in their drinking
      water (week 2) to induce inflammation-associated colon tumors. eUBM was performed
      simultaneously with colonoscopy at weeks 13, 17-20 and 21. A 3.6-F diameter 40
      MHz mini-probe catheter was used for eUBM imaging. The ultrasound mini-probe
      catheter was inserted into the accessory channel of a pediatric flexible
      bronchofiberscope, allowing simultaneous acquisition of colonoscopic and eUBM
      images. During image acquisition, the mice were anesthetized with isoflurane and
      kept in a supine position over a stainless steel heated surgical waterbed at 37 
      degrees C. Both eUBM and colonoscopic images were captured and stored when a
      lesion was detected by colonoscopy or when the eUBM image revealed a modified
      colon wall anatomy. During the procedure, the colon was irrigated with water that
      was injected through a flush port on the mini-probe catheter and that acted as
      the ultrasound coupling medium between the transducer and the colon wall. Once
      the acquisition of the last eUBM/colonoscopy section for each animal was
      completed, the colons were fixed, paraffin-embedded, and stained with hematoxylin
      and eosin. Colon images acquired at the first time-point for each mouse were
      compared with subsequent eUBM/colonoscopic images of the same sites obtained in
      the following acquisitions to evaluate lesion progression. RESULTS: All 10 mice
      had eUBM and colonoscopic images acquired at week 13 (the first time-point). Two
      animals died immediately after the first imaging acquisition and, consequently,
      only 8 mice were subjected to the second eUBM/colonoscopy imaging acquisition (at
      the second time-point). Due to the advanced stage of colonic tumorigenesis, 5
      animals died after the second time-point image acquisition, and thus, only three
      were subjected to the third eUBM/colonoscopy imaging acquisition (the third time
      point). eUBM was able to detect the four layers in healthy segments of colon: the
      mucosa (the first hyperechoic layer moving away from the mini-probe axis),
      followed by the muscularis mucosae (hypoechoic), the submucosa (the second
      hyperechoic layer) and the muscularis externa (the second hypoechoic layer).
      Hypoechoic regions between the mucosa and the muscularis externa layers
      represented lymphoid infiltrates, as confirmed by the corresponding histological
      images. Pedunculated tumors were represented by hyperechoic masses in the mucosa
      layer. Among the lesions that decreased in size between the first and third time
      points, one of the lesions changed from a mucosal hyperplasia with ulceration at
      the top to a mucosal hyperplasia with lymphoid infiltrate and, finally, to small
      signs of mucosal hyperplasia and lymphoid infiltrate. In this case, while lesion
      regression and modification were observable in the eUBM images, colonoscopy was
      only able to detect the lesion at the first and second time-points, without the
      capacity to demonstrate the presence of lymphoid infiltrate. Regarding the
      lesions that increased in size, one of them started as a small elevation in the
      mucosa layer and progressed to a pedunculated tumor. In this case, while eUBM
      imaging revealed the lesion at the first time-point, colonoscopy was only able to
      detect it at the second time-point. All colonic lesions (tumors, lymphoid
      infiltrate and mucosal thickening) were identified by eUBM, while colonoscopy
      identified just 76% of them. Colonoscopy identified all of the colonic tumors but
      failed to diagnose lymphoid infiltrates and increased mucosal thickness and
      failed to differentiate lymphoid infiltrates from small adenomas. During the
      observation period, most of the lesions (approximately 67%) increased in size,
      approximately 14% remained unchanged, and 19% regressed. CONCLUSION: Combining
      eUBM with colonoscopy improves the diagnosis and the follow-up of mouse colonic
      lesions, adding transmural assessment of the bowel wall.

PMID- 24307801
TI  - Effects of disease severity and necrosis on pancreatic dysfunction after acute
      pancreatitis.
AB  - AIM: To evaluate the effects of disease severity and necrosis on organ
      dysfunctions in acute pancreatitis (AP). METHODS: One hundred and nine patients
      treated as AP between March 2003 and September 2007 with at least 6 mo follow-up
      were included. Patients were classified according to severity of the disease,
      necrosis ratio and localization. Subjective clinical evaluation and fecal
      pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and
      oral glucose tolerance test was completed for endocrine dysfunction. The
      correlation of disease severity, necrosis ratio and localization with exocrine
      and endocrine dysfunction were investigated. RESULTS: There were 58 male and 51
      female patients, and mean age was 56.5 +/- 15.7. Of the patients, 35.8% had
      severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was
      identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP
      (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP
      and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels
      were lower than the others (P < 0.05 and 0.001 respectively) and in patients
      having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower
      than 200 MUg/g stool. Forty percent of the patients who had undergone
      necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more
      significant in patients with SAP and NAP (P < 0.001). All of the patients in the
      necrosectomy group had endocrine dysfunction. CONCLUSION: Patients with SAP, NAP,
      pancreatic head necrosis and necrosectomy should be followed for pancreatic
      functions.

PMID- 24307802
TI  - Shugan-decoction relieves visceral hyperalgesia and reduces TRPV1 and SP colon
      expression.
AB  - AIM: To evaluate the therapeutic effect of Shugan-decoction (SGD) on visceral
      hyperalgesia and colon gene expressions using a rat model. METHODS: Ninety-six
      adult male Wistar rats were randomized into six equal groups for assessment of
      SGD effects on psychological stress-induced changes using the classic water
      avoidance stress (WAS) test. Untreated model rats were exposed to chronic (1 h/d
      for 10 d consecutive) WAS conditions; experimental treatment model rats were
      administered with intragastric SGD at 1 h before WAS on consecutive days 4-10
      (low-dose: 0.1 g/mL; mid-dose: 0.2 g/mL; high-dose: 0.4 g/mL); control treatment
      model rats were similarly administered with the irritable bowel syndrome drug,
      dicetel (0.0042 g/mL); untreated normal control rats received no drug and were
      not subjected to the WAS test. At the end of the 10-d WAS testing period, a semi
      quantitative measurement of visceral sensitivity was made by assessing the
      abdominal withdrawal reflex (AWR) to colorectal balloon-induced distension (at 5
      mmHg increments) to determine the pain pressure threshold (PPT, evidenced by pain
      behavior). Subsequently, the animals were sacrificed and colonic tissues
      collected for assessment of changes in expressions of proteins related to
      visceral hypersensitivity (transient receptor potential vanilloid 1, TRPV1) and
      sustained visceral hyperalgesia (substance P, SP) by immunohistochemistry and
      real-time polymerase chain reaction. Inter-group differences were assessed by
      paired t test or repeated measures analysis of variance. RESULTS: The WAS test
      successfully induced visceral hypersensitivity, as evidenced by a significantly
      reduced AWR pressure in the untreated model group as compared to the untreated
      normal control group (190.4 +/- 3.48 mmHg vs 224.0 +/- 4.99 mmHg, P < 0.001). SGD
      treatments at mid-dose and high-dose and the dicetel treatment significantly
      increased the WAS-reduced PPT (212.5 +/- 2.54, 216.5 +/- 3.50 and 217.7 +/- 2.83
      mmHg respectively, all P < 0.001); however, the low-dose SGD treatment produced
      no significant effect on the WAS-reduced PPT (198.3 +/- 1.78 mmHg, P > 0.05).
      These trends corresponded to the differential expressions observed for both TRPV1
      protein (mid-dose: 1.64 +/- 0.08 and high-dose: 1.69 +/- 0.12 vs untreated model:
      3.65 +/- 0.32, P < 0.001) and mRNA (0.44 +/- 0.16 and 0.15 +/- 0.03 vs 1.39 +/-
      0.15, P < 0.001) and SP protein (0.99 +/- 0.20 and 1.03 +/- 0.23 vs 2.03 +/-
      0.12, P < 0.01) and mRNA (1.64 +/- 0.19 and 1.32 +/- 0.14 vs 2.60 +/- 0.33, P <
      0.05). These differential expressions of TRPV1 and SP related to mid- and high
      dose SGD treatments were statistically similar to the changes induced by dicetel
      treatment. No signs of overt damage to the rat system were observed for any of
      the SGD dosages. CONCLUSION: Shugan-decoction can reduce chronic stress-induced
      visceral hypersensitivity in rats, and the regulatory mechanism may involve
      mediating the expressions of TRPV1 and SP in colon tissues.

PMID- 24307803
TI  - Clinical characteristics and prognosis of young patients with colorectal cancer
      in Eastern China.
AB  - AIM: To explore the clinical characteristics and prognosis of young patients with
      colorectal cancer patients in Eastern China. METHODS: A total of 1335 patients
      with colorectal cancer treated from December 1985 to December 2005 at the Second
      Affiliated Hospital of Zhejiang University School of Medicine were studied
      retrospectively. The patients were divided into two groups, a younger group (aged
      <= 30 years) and an older group (aged > 30 years), and comparison was made in the
      clinical characteristics and prognosis between the two groups. Chi-square test
      was used for data analysis of all categorical variables, and overall survival
      (OS) was calculated by the Kaplan-Meier method. A multivariate analysis was
      performed using the Cox model. RESULTS: There were 42 (3.1%) and 1293 (96.9%)
      cases in the younger group and older group, respectively. Univariate analysis
      showed that the 5- and 10-year OS in the younger group were 33.9% and 26.1%,
      respectively, and those in the older group were 60.1% and 52.2%, respectively.
      Younger group had poor survival (chi(2) = 14.146, P = 0.000). Multivariate
      analysis revealed that age was not a dependent factor for prognosis (OR = 0.866,
      95%CI: 0.592-1.269, P = 0.461). Stratified analysis indicated that in stage III
      and IV disease, the 5- and 10-year OS were 24.6% and 14.8% in the younger group,
      and 40.4% and 33.3% in the older group, respectively, with a significant
      difference between the two groups (chi(2) = 5.101, P = 0.024). In the subgroup of
      radical surgery, the 5- and 10-year OS were 44.3% and 34.2% in the younger group,
      and 69.6% and 60.5% in the older group, with a difference being significant
      between the two groups (chi(2) = 7.830, P = 0.005). CONCLUSION: Compared with
      older patients, the younger patients have lower survival, especially in the
      subgroups of stage III and IV disease and radical surgery.

PMID- 24307804
TI  - Clinical effects and complications of TIPS for portal hypertension due to
      cirrhosis: a single center.
AB  - AIM: To determine the clinical effects and complications of transjugular
      intrahepatic portosystemic shunt (TIPS) for portal hypertension due to cirrhosis.
      METHODS: Two hundred and eighty patients with portal hypertension due to
      cirrhosis who underwent TIPS were retrospectively evaluated. Portal trunk
      pressure was measured before and after surgery. The changes in hemodynamics and
      the condition of the stent were assessed by ultrasound and the esophageal and
      fundic veins observed endoscopically. RESULTS: The success rate of TIPS was
      99.3%. The portal trunk pressure was 26.8 +/- 3.6 cmH2O after surgery and 46.5 +/
      3.4 cmH2O before surgery (P < 0.01). The velocity of blood flow in the portal
      vein increased. The internal diameters of the portal and splenic veins were
      reduced. The short-term hemostasis rate was 100%. Esophageal varices disappeared
      completely in 68% of patients and were obviously reduced in 32%. Varices of the
      stomach fundus disappeared completely in 80% and were obviously reduced in 20% of
      patients. Ascites disappeared in 62%, were markedly reduced in 24%, but were
      still apparent in 14% of patients. The total effective rate of ascites reduction
      was 86%. Hydrothorax completely disappeared in 100% of patients. The incidence of
      post-operative stent stenosis was 24% at 12 mo and 34% at 24 mo. The incidence of
      post-operative hepatic encephalopathy was 12% at 3 mo, 17% at 6 mo and 19% at 12
      mo. The incidence of post-operative recurrent hemorrhage was 9% at 12 mo, 19% at
      24 mo and 35% at 36 mo. The cumulative survival rate was 86% at 12 mo, 81% at 24
      mo, 75% at 36 mo, 57% at 48 mo and 45% at 60 mo. CONCLUSION: TIPS can effectively
      lower portal hypertension due to cirrhosis. It is significantly effective for
      hemorrhage of the digestive tract due to rupture of esophageal and fundic veins
      and for ascites and hydrothorax caused by portal hypertension.

PMID- 24307805
TI  - "Metroticket" predictor for assessing liver transplantation to treat
      hepatocellular carcinoma: a single-center analysis in mainland China.
AB  - AIM: To validate the "Metroticket" predictor using a large cohort of liver
      transplantation (LT) patients with hepatocellular carcinoma (HCC) in China.
      METHODS: In total, 230 cases of LT for HCC treatment at our center, from July
      2000 to August 2008, were included in the present study. The predicted 1-, 3- and
      5-year post-LT survival rates were calculated using the Metroticket model
      (http://89.96.76.14/metroticket/calculator/). The predicted and observed long
      term survival rates were then compared and analyzed. RESULTS: The predicted
      survival rates for all 230 cases, as calculated by the Metroticket model, were
      64.7% and 56.2% at 3 and 5 years, respectively, and the observed survival rates
      for these patients were 71.3% and 57.8%, respectively. For the 23 cases with
      macrovascular invasion, the predicted 5-year survival rate was 43.5%, whereas the
      observed 5-year survival rate was only 8.7%. For the 42 cases with microvascular
      invasion but an absence of macrovascular invasion, the predicted 5-year survival
      rate was 44.9%, and the observed 5-year survival rate was 50%. For the remaining
      165 patients without any vascular invasion, the predicted 5-year survival rate
      was 65.8%, and the observed 5-year survival rate was 66.7%. CONCLUSION: The
      Metroticket model can be used to accurately predict survival in HCC-related LT
      cases with an absence of macrovascular invasion.

PMID- 24307806
TI  - Decreased histone H2B monoubiquitination in malignant gastric carcinoma.
AB  - AIM: To investigate H2B monoubiquitination (uH2B) and H3K4 di- and tri
      methylation (H3K4-2me, H3K4-3me) levels and their clinical significance in
      gastric cancer (GC). METHODS: Immunohistochemistry (IGC) was used to detect the
      differential levels of uH2B, H3K4-2me and H3K4-3me modifications in GC specimens
      from chemo/radiotherapy-naive patients who underwent potentially curative
      surgical resection (n = 159) and in a random sampling of non-tumor gastric
      epithelium specimens (normal controls, n = 20). The immunohistochemistry (IHC)
      detected modifications were classified as negative, low-level, or high-level
      using a dual-rated (staining intensity and percentage of positively-stained
      cells) semi-quantitative method. The relationships between uH2B modification
      levels and clinicopathological parameters of GC were assessed by a Wilcoxon rank
      sum test (pairwise comparisons) and the Kruskal-Wallis H test (multiple
      comparisons). The correlation between uH2B modification and survival was
      estimated by Kaplan-Meier analysis, and the role of uH2B as an independent
      prognostic factor for survival was assessed by multivariate Cox regression
      analysis. RESULTS: The presence and level of H3K4-2me and H3K4-3me IHC staining
      was similar between the normal controls and GC specimens. In contrast, the level
      of uH2B was significantly lower in the malignant gastric tissues (vs normal
      control tissues) and decreased along with increases in dedifferentiation (well
      differentiated > moderately differentiated > poorly differentiated). The level of
      uH2B correlated with tumor differentiation (P < 0.001), Lauren's diffuse- and
      intestinal-type classification (P < 0.001), lymph node metastasis (P = 0.049) and
      tumor-node-metastasis stage (P = 0.005). Patients with uH2B+ staining had higher
      5-year survival rates than patients with uH2B-staining (52.692 +/- 2.452 vs
      23.739 +/- 5.207, P < 0.001). The uH2B level was an independent prognostic factor
      for cancer-specific survival (95%CI: 0.237-0.677, P = 0.001). CONCLUSION: uH2B
      displays differential IHC staining patterns corresponding to progressive stages
      of GC. uH2B may contribute to tumorigenesis and could be a potential therapeutic
      target.

PMID- 24307807
TI  - siRNA-targeted inhibition of growth hormone receptor in human colon cancer SW480
      cells.
AB  - AIM: To determine the effects of RNAi-mediated inhibition of the growth hormone
      receptor (GHR) gene on tumors and colon cancer cells in vivo. METHODS:
      Construction of a eukaryotic vector for human GHR expression, the pcDNA6.2
      GW/EmGFP-small interfering RNAs (siRNAs)-GHR plasmid, was used to inhibit GHR
      expression. Thirty-six BALB/c nude mice were randomly divided into groups and
      treated with normal saline (NS), recombinant plasmid (G2), growth hormone (GH), 5
      fluorouracil (FU), G2+FU or G2+FU+GH. Each nude mouse was subcutaneously
      inoculated with 1 * 10(7) human colon cancer SW480 cells; the nude mice were
      weighed before inoculation and on the 2(nd), 5(th), 8(th), 11(th), 14(th) and
      17(th) day after inoculation. All nude mice were sacrificed after 17 d. Each
      subcutaneous tumor was removed and studied. Tumor volume was measured on the
      5(th), 8(th), 11(th), 14(th) and 17(th) day after inoculation. The expression of
      GHR protein in the tumor tissue was detected by Western blotting analysis, and
      the differences in GHR mRNA expression in the tumor tissue were detected by real
      time quantitative reverse transcription-polymerase chain reaction. RESULTS:
      Compared to the control group, the weights of the inoculated nude mice on the
      17(th) day after inoculation were: G2: 21.60 +/- 0.71 g, GH: 21.64 +/- 0.45 g,
      FU: 18.94 +/- 0.47 g, FU+G2: 19.40 +/- 0.60 g, G2+FU+GH: 21.04 +/- 0.78 g vs NS:
      20.68 +/- 0.66 g, P < 0.05; the tumor volumes after the subcutaneous inoculation
      were: G2: 9.71 +/- 3.82 mm(3), FU: 11.54 +/- 2.42 mm(3), FU+G2: 11.42 +/- 1.11
      mm(3), G2+FU+GH: 10.47 +/- 1.02 mm(3) vs NS: 116.81 +/- 10.61 mm(3), P < 0.05.
      Compared to the GH group, the tumor volumes were significantly decreased in the
      experimental groups. The GHR protein expression (G2: 0.39 +/- 0.02, FU: 0.40 +/-
      0.02, FU+G2: 0.38 +/- 0.01, G2+FU+GH: 0.39 +/- 0.01 vs NS: 0.94 +/- 0.02, P <
      0.05) and the GHR mRNA expression (G2: 14.12 +/- 0.10, FU: 15.15 +/- 0.44, FU+G2:
      16.46 +/- 0.27, G2+FU+GH: 15.37 +/- 0.57 vs NS: 12.63 +/- 0.14, P < 0.05) were
      significantly decreased and increased, respectively, in the experimental groups.
      CONCLUSION: Inhibition of GHR in human colon cancer SW480 cells resulted in anti
      tumor effects in nude mice.

PMID- 24307808
TI  - Laparoscopic vs open total gastrectomy for gastric cancer: a meta-analysis.
AB  - AIM: To conduct a meta-analysis comparing laparoscopic total gastrectomy (LTG)
      with open total gastrectomy (OTG) for the treatment of gastric cancer. METHODS:
      Major databases such as Medline (PubMed), Embase, Academic Search Premier
      (EBSCO), Science Citation Index Expanded and the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library were searched for studies
      comparing LTG and OTG from January 1994 to May 2013. Evaluated endpoints were
      operative, postoperative and oncological outcomes. Operative outcomes included
      operative time and intraoperative blood loss. Postoperative recovery included
      time to first flatus, time to first oral intake, hospital stay and analgesics
      use. Postoperative complications comprised morbidity, anastomotic leakage,
      anastomotic stenosis, ileus, bleeding, abdominal abscess, wound problems and
      mortality. Oncological outcomes included positive resection margins, number of
      retrieved lymph nodes, and proximal and distal resection margins. The pooled
      effect was calculated using either a fixed effects or a random effects model.
      RESULTS: Fifteen non-randomized comparative studies with 2022 patients were
      included (LTG - 811, OTG - 1211). Both groups had similar short-term oncological
      outcomes, analgesic use (WMD -0.09; 95%CI: -2.39-2.20; P = 0.94) and mortality
      (OR = 0.74; 95%CI: 0.24-2.31; P = 0.61). However, LTG was associated with a lower
      intraoperative blood loss (WMD -201.19 mL; 95%CI: -296.50--105.87 mL; P < 0.0001)
      and overall complication rate (OR = 0.73; 95%CI: 0.57-0.92; P = 0.009); fewer
      wound-related complications (OR = 0.39; 95%CI: 0.21-0.72; P = 0.002); a quicker
      recovery of gastrointestinal motility with shorter time to first flatus (WMD 
      0.82; 95%CI: -1.18--0.45; P < 0.0001) and oral intake (WMD -1.30; 95%CI: -1.84-
      0.75; P < 0.00001); and a shorter hospital stay (WMD -3.55; 95%CI: -5.13--1.96; P
      < 0.0001), albeit with a longer operation time (WMD 48.25 min; 95%CI: 31.15
      65.35; P < 0.00001), as compared with OTG. CONCLUSION: LTG is safe and effective,
      and may offer some advantages over OTG in the treatment of gastric cancer.

PMID- 24307809
TI  - Effectiveness of interferon-gamma release assays for differentiating intestinal
      tuberculosis from Crohn's disease: a meta-analysis.
AB  - AIM: To investigate the clinical usefulness of interferon-gamma release assays
      (IGRAs) in the differential diagnosis of intestinal tuberculosis (ITB) from
      Crohn's disease (CD) by meta-analysis. METHODS: A systematic search of English
      language studies was performed. We searched the following databases: Medline,
      Embase, Web of Science and the Cochrane Library. The Standards for Reporting
      Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic
      Accuracy tool were used to assess the methodological quality of the studies.
      Sensitivity, specificity, and other measures of the accuracy of IGRAs in the
      differential diagnosis of ITB from CD were pooled and analyzed using random
      effects models. Receiver operating characteristic curves were applied to
      summarize overall test performance. Two reviewers independently judged study
      eligibility while screening the citations. RESULTS: Five studies met the
      inclusion criteria. The average inter-rater agreement between the two reviewers
      for items in the quality checklist was 0.95. Analysis of IGRAs for the
      differential diagnosis of ITB from CD produced summary estimates as follows:
      sensitivity, 0.74 (95%CI: 0.68-0.80); specificity, 0.87 (95%CI: 0.82-0.90);
      positive likelihood ratio, 5.98 (95%CI: 3.79-9.43); negative likelihood ratio,
      0.28 (95%CI: 0.18-0.43); and diagnostic odds ratio, 26.21 (95%CI: 14.15-48.57).
      The area under the curve was 0.92. The evaluation of publication bias was not
      significant (P = 0.235). CONCLUSION: Although IGRAs are not sensitive enough,
      they provide good specificity for the accurate diagnosis of ITB, which may be
      helpful in the differential diagnosis of ITB from CD.

PMID- 24307810
TI  - Seven synchronous early gastric cancer with 28 lymph nodes metastasis.
AB  - An 85 year male patient complaining epigastric discomfort was admitted. From the
      esophagogastroduodenoscopy, three early gastric cancer (EGCa) lesions had been
      identified and these were diagnosed as adenocarcinoma with poorly differentiated
      cell type. The patient underwent operation. From the post-operative mapping,
      however, additional 4 EGCa lesions were found, and the patient was diagnosed with
      7 synchronous EGCa. Out of the 7 EGCa lesions, 6 had shown invasion only to the
      mucosal layer and one had shown invasion into the 1/3 layer of submucosa. In
      spite of such superficial invasions, 28 of 48 lymph nodes had been identified as
      metastases. The multiple lesions of EGCa do not increase the risk of lymph node
      metastasis, but if their differentiations are poor or if they have lympho
      vascular invasion, multiple lymph node metastases could incur even if the depth
      of invasion is limited to the mucosal layer or the upper portion of the
      submucosal layer. 

PMID- 24307811
TI  - Small cell carcinoma of the liver and biliary tract without jaundice.
AB  - An 80-year-old woman presenting with chest pain was found to have a large,
      lobulated soft tissue mass in the liver and nearby tissues on abdominal computed
      tomography (CT). The tumor had invaded the common hepatic artery and main portal
      vein. Jaundice developed 4 wk later, at which point, a pancreas and biliary CT
      scan revealed a large mass in the right lobe of the liver and a hilar duct
      obstruction, which was found to be a small cell carcinoma. Despite its rarity,
      liver and bile duct small cell carcinoma should be considered in the differential
      diagnosis of atypical chest pain without jaundice. 

PMID- 24307812
TI  - Malignant paraganglioma of the rectum: the first case report and a review of the
      literature.
AB  - Paragangliomas typically develop in the extra-adrenal sites along the sympathetic
      and/or the parasympathetic chain. Occasionally, the tumors may arise in some
      exotic sites, including the head and neck region and the urogenital tract.
      Paraganglioma presenting as a primary rectal neoplasm has not been well described
      in the literature. Here, we report the first case of malignant paraganglioma
      arising in the rectum of a 37-year-old male. He presented to the clinic because
      of hematochezia with tenesmus. The anorectal digital examination and colonoscopic
      examination revealed a polypoid mass of the rectum, measuring approximately 4 cm
      in diameter. The overall morphology and immunophenotype were consistent with a
      typical paraganglioma. However, the tumor exhibited features suggestive of
      malignant potential, including local extension into adjacent adipose tissue,
      nuclear pleomorphism, confluent tumor necrosis, vascular invasion and metastases
      to regional lymph nodes. In conclusion, we present the first case of rectal
      malignant paraganglioma. Due to the unexpected occurrence in this region,
      malignant paraganglioma may be misdiagnosed as other tumors with overlapping
      features; in particular, a neuroendocrine tumor of epithelial origin. Because of
      the differences in treatment, separating paraganglioma from its mimics is
      imperative. Combination of morphology with judicious immunohistochemical study is
      helpful in obtaining the correct diagnosis. 

PMID- 24307813
TI  - Ileal conduit stomal variceal bleeding managed by endovascular embolization.
AB  - Ileal conduit stomal varices are rare, and may result in bleeding. The standard
      treatment modality for management of this type of hemorrhage has not been
      established. We present the case of a 70-year-old woman with progressive ileal
      conduit stomal variceal bleeding which was successfully managed by endovascular
      embolization via the transjugular transhepatic approach. In conclusion,
      transjugular transhepatic endovascular embolization is a good choice in patients
      with ileal conduit stomal variceal bleeding who have failed conservative therapy.

PMID- 24307814
TI  - Hydroxycitric acid does not promote inflammation or liver toxicity.
AB  - Garcinia cambogia extract (GC) with its active component consisting of
      hydroxycitric acid (HCA) is widely utilized for weight loss. Various HCA salts
      are available, including calcium, magnesium, potassium and mixtures of these.
      Experimentally, these salts exhibit different properties with some, but not all,
      improving glucose tolerance and blood pressure. Recently, obesity-prone C57BL/6J
      mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without GC (1%, w/w)
      for 16 wk. The active arm reduced visceral fat, adipocyte size and serum glucose,
      yet purportedly also exhibited hepatic collagen accumulation, lipid peroxidation
      and increased mRNA levels of genes related to oxidative stress. The latter
      findings are at odds with a large body of animal and human studies that have been
      conducted on the safety and efficacy of HCA. This literature shows HCA to be
      protective against the liver toxicity associated with ethanol and dexamethasone
      administration, and to maintain serum aspartate aminotransferase, alanine
      aminotransferase and alkaline phosphatase at near normal levels. In both animal
      and clinical literature, elevated intakes of HCA per se have not led to signs of
      inflammation or hepatotoxicity. The compound has been found to reduce markers of
      inflammation in brain, intestines, kidney and serum. 

PMID- 24307815
TI  - ANALYSIS OF MULTIVARIATE FAILURE TIME DATA USING MARGINAL PROPORTIONAL HAZARDS
      MODEL.
AB  - The marginal proportional hazards model is an important tool in the analysis of
      multivariate failure time data in the presence of censoring. We propose a method
      of estimation via the linear combinations of martingale residuals. The estimation
      and inference procedures are easy to implement numerically. The estimation is
      generally more accurate than the existing pseudo-likelihood approach: the size of
      efficiency gain can be considerable in some cases, and the maximum relative
      efficiency in theory is infinite. Consistency and asymptotic normality are
      established. Empirical evidence in support of the theoretical claims is shown in
      simulation studies.

PMID- 24307816
TI  - Sequential Analysis of the Cox Model under Response Dependent Allocation.
AB  - Sellke and Siegmund (1983) developed the Brownian approximation to the Cox
      partial likelihood score as a process of calendar time, laying the foundation for
      group sequential analysis of survival studies. We extend their results to cover
      situations in which treatment allocations may depend on observed outcomes. The
      new development makes use of the entry time and calendar time along with the
      corresponding sigma-filtrations to handle the natural information accumulation.
      Large sample properties are established under suitable regularity conditions.

PMID- 24307817
TI  - Could public health problem from meningococcal disease be eliminated?

PMID- 24307819
TI  - Effects of information dissemination using video of indigenous language on 11-12
      years children's dental health.
AB  - BACKGROUND: Videos as a medium of health education are useful tools. This study
      evaluated the effectiveness of a dental health education video in the Yoruba
      language (spoken in southwestern Nigeria) targeted at children from the lower
      socioeconomic class. METHODS: An interventional study was conducted among 120
      children aged 11 and 12 years, randomly selected from three public primary
      schools in Ibadan, Nigeria. Participants were assigned into three study groups:
      group 1 watched the video, group 2 received verbal dental health education in the
      Yoruba language and group 3 were the control. Following this, each participant
      received a full mouth prophylaxis, and six weeks later, their oral hygiene was
      assessed using the Simplified Oral Hygiene Index of Greene and Vermillion.
      RESULTS: A mean debris score of (1.11), (1.04) and (1.57) was recorded for the
      video, verbal and control groups respectively (p<0.001). The mean calculus index
      score was lowest among the verbal group (0.56), followed by the video group
      (0.75) and highest among the control (1.16) (p<0.001). However, multivariate
      analysis, controlling for child's age and fathers education, revealed that oral
      hygiene of the participants in the video group was significantly better by 28.6%
      compared to the control group while in the verbal education group there was an
      improvement of 23.4 % in contrast to the control. CONCLUSION: This study
      demonstrated that a culturally appropriate video in an indigenous language can
      significantly improve oral hygiene among school children from the lower
      socioeconomic group in Nigeria.

PMID- 24307818
TI  - Age at menarche among in-school adolescents in Sawla Town, South Ethiopia.
AB  - BACKGROUND: Although a declining trend in age at menarche has been observed in
      developed countries over decades commonly attributed to childhood excessive
      weight gain and sedentary life, little is known about this case in the developing
      countries. METHODS: A cross-sectional study design and multistage sampling was
      used to include 660 school adolescents for analysis. Data collection included
      weight and height measurements. Multinomial logistic regression analyses were
      done for early and late age of menarche, in reference to average age at menarche,
      to measure the association of age at menarche with some socio-demographic
      variables and body habits. RESULTS: The mean age at menarche was 13.9+/-1.2 years
      (95%CI, 13.8-14.0). The menarche ages ranged between 10 and 12 years for 10.5%,
      13 and 14 years for 54.5%, and 15+ years for 35%. Low menarche age was
      independently associated with high calorie consumption, high protein diet, more
      coffee intake, low physical activity and parents' low educational background. Low
      body mass index, low parents' income, exercise, and Amhara ethnic background were
      associated with late menarche age. COCLUSION: The mean menarche age found in this
      study was higher than the report from developed countries. But, the proportion of
      adolescents with low menarche age was comparable with reports from developed
      countries. Inactive adolescents were more likely to see menarche earlier than
      average age. Healthy eating habits, regular exercise and nutrition education need
      to be promoted among school children.

PMID- 24307820
TI  - Bacterial profile and antimicrobial susceptibility pattern of isolates among burn
      patients at Yekatit 12 Hospital Burn Center, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Infection is a common cause of morbidity and mortality in burn
      patients. Clinical diagnosis of bacteremia and/or sepsis in burn patients is
      difficult for a number of reasons. It could be symptomatic and/or asymptomatic as
      a result of immune deficiency secondary to thermal injury. METHODS: A cross
      sectional study was conducted at Yekatit 12 Hospital Burn Center. Blood specimen
      and wound swab were collected from burn patients and were cultured by
      conventional method. Sensitivity/susceptibility pattern of the isolates was
      determined by disc diffusion method. Some of the risk factors of bacteremia like
      prior antibiotic use and total body surface area burn were also determined.
      RESULTS: Fifty patients were enrolled in the study of whom 21(42%) were found
      bacteremic. Five different bacteria were isolated from blood specimen. Coagulase
      negative Staphylococci, 9(42.8%), S. aureus, 8(38.2%), Bacillus spps, 2(9.52%),
      K. pneumoniae, 1(4.8%), and P. aeruginosa, 1(4.8%), were frequent isolates. From
      wound swab, S. aureus, (34.04%), and P. aeruginosa, (31.8%), were predominant.
      Antimicrobial resistance was observed for Ampicillin, (77.4%), Doxycycline,
      (74.0), Nalidixic acid, (70.5%), Penicillin G, (68.2%), and tetracycline,
      (67.5%). Total body surface area of burn >= 15% was found as a risk factor for
      bacteremia. CONCLUSION: Bacteremia was detected at a rate of 42% among burn
      patients. Frequent isolates were S. aureus, (34.04%), and P. aeruginosa, (31.8%).
      About 82.16% of the isolates showed multiple resistances. In light of our
      findings, regular antibiotic resistance test has to be done for each patient in
      order to select an appropriate antimicrobial agent.

PMID- 24307821
TI  - Hepatotoxicity and associated risk factors in HIV-infected patients receiving
      antiretroviral therapy at Felege Hiwot Referral Hospital, Bahirdar, Ethiopia.
AB  - BACKGROUND: In Human Immunodeficiency Virus (HIV) infected patients on
      antiretroviral treatment (ART), hepatotoxicity is life threatening. Its outcome
      may lead to liver failure and death. This study was conducted to determine the
      rate and determinants of elevated alanine amino transferase (ALT) (referred as
      >40IU/L for both males and females). METHODS: A cross sectional study was
      conducted on HIV infected individuals who are on ART and suspected of drug
      resistance at Felege Hiwot Referral Hospital, Bahir Dar from July to December
      2012. Venous bloods were collected from each patient and processed parallely to
      determine ALT, number of HIV RNAs, CD4 and CD8 T cells count, anti hepatitis C
      virus (HCV) and hepatitis B surface antigen. RESULTS: Out of 269 HIV infected
      patients receiving ART, 32% were confirmed of grades 1-4 levels of elevated ALT.
      The rate of severe hepatotoxicity (grade 3 and 4) was 1.84%. Patients with
      increased CD8 T cell counts (P=0.011; AOR=1.82; CI: 1.12 -2.54), alcohol over use
      (P=0.014; AOR = 1.23; CI: 1.36-3.29) and detectable HIV-1 RNA copies (P=0.015;
      AOR=2.07; CI: 1.15-3.74) independently predicts the elevation of ALT.
      CONCLUSIONS: In HIV infected patients on ART, extreme elevations of ALT were
      infrequent but minor elevations were common so that patient-linked variables such
      as use of alcohol intake must be taken in to account for better clinical
      management of ART patients. The role of active HCV co-infection on the treatment
      outcome of ART should be further studied.

PMID- 24307822
TI  - Medication non-adherence among adult psychiatric out patients in Jimma University
      Specialized Hospital, Southwest Ethiopia.
AB  - BACKGROUND: Information on adherence of adult psychiatric patients to biological
      modes of treatment is scarce in Ethiopia. Knowledge on adherence is essential in
      terms of future prognosis, quality of life and functionality of such patients.
      This study was conducted to assess the magnitude and associated factors of non
      adherence to medication. METHODS: A hospital based cross-sectional study was
      conducted in November 2011 at the psychiatry facility of Jimma University
      Specialized Hospital, which provides service to more than 10 mill people. A
      sample of 422 adults with psychiatric illness in the follow-up outpatients was
      selected consecutively. Data was collected using a pre-tested questionnaire by
      face-to-face interview and from patient medical records. The four-item Morisky
      scale was used to assess degree of medication adherence. Data was analyzed using
      SPSS version 16 and descriptive, chi-square test and logistic regression
      statistical methods were used. P-Value of less than 0.05 was considered as
      statistically significant in the final model. RESULTS: Out of the 422 patients,
      40.3% were females and 59.7% males. The prevalence rate for non-adherence was
      41.2%, non-affective psychoses diagnosis contributing the highest rate (44.5%).
      From the total non-adherent respondents, 78.2% attributed their non-adherence to
      forgetting. Irregular follow-up, poor social support and complex drug regimen
      were independently associated variables with non-adherence. CONCLUSIONS: The
      result of the study showed that non-adherence among psychiatric patients in
      Southwest Ethiopia is high and revealed possible associated factors. Adherence
      needs integrated efforts in creating a mechanism in enhancing regular follow-up,
      informal social support system and ongoing awareness creation among
      professionals.

PMID- 24307823
TI  - Soil transmitted helminths and associated factors among schoolchildren in
      government and private primary school in Jimma Town, Southwest Ethiopia.
AB  - BACKGROUND: Soil transmitted helminth infections are among the most common human
      infections. They are distributed throughout the world with high prevalence rates
      in tropical and sub-tropical countries mainly because of lack of adequate
      sanitary facilities, inappropriate waste disposal systems, lack of safe water
      supply, and low socio-economic status. METHODS: A comparative cross sectional
      study was conducted from December 2011 to June 2012 to determine and assess the
      prevalence of soil transmitted helminths and their associated factors among
      government and private primary school children. Stool samples were collected from
      369 randomly selected children and examined microscopically for eggs of soil
      transmitted helminth following McMaster techniques. Soil samples were collected
      from different parts of the school compound and microscopic examination was
      performed for eggs of the helminths using sodium nitrate flotation technique.
      RESULTS: The overall prevalence rate of soil transmitted helminth infections in
      private and government schools was 20.9% and 53.5% respectively. T. trichiura was
      the most common soil transmitted helminth in both schools while hookworm
      infections were identified in government school students only. Type of school and
      sex were significantly associated with soil transmitted helminth. Soil
      contamination rate of the school compounds was 11.25% with predominant parasites
      of A. lumbricoides. CONCLUSION: Higher prevalence of soil transmitted helminth
      infection was found among government school students. Thus, more focus, on
      personal hygiene and sanitary facilities, should be given to children going to
      government schools.

PMID- 24307824
TI  - Quality of family planning services in primary health centers of Jimma Zone,
      Southwest Ethiopia.
AB  - BACKGROUND: Good quality of care in family planning (FP) services help
      individuals and couples to meet their reproductive health needs safely and
      effectively. Therefore, assessment and improvement of the quality of family
      planning services could enhance family planning services utilization. This study
      was thus conducted to assess the quality of family planning services in primary
      health centers of Jimma Zone, Southwest Ethiopia. METHODS: A cross-sectional
      facility based study was conducted from March 1(st)-25(th), 2011 among family
      planning clients of government primary health care centers in southwest Ethiopia.
      Exit interview of 301 family planning clients identified through systematic
      random sampling technique was carried out using a pre-tested structured
      questionnaire. Availability of resources was checked using provider interview and
      inventory checklist. Moreover, a total of 150 consultation sessions were observed
      using checklist. Descriptive statistics and linear regression coefficients were
      generated to meet the objective of the study. RESULTS: There was a shortage of
      some medical equipment, trained staffs, and information education and
      communication materials (IEC) in all of the family planning clinics. The mean
      waiting time at the service delivery points and consultation duration were 16.4
      and 10.5 minutes, respectively. The providers used at least one information
      education and communication material in 33.3% of the consultation sessions. The
      overall satisfaction score was 8.64. Clients' perception on adequacy of
      information during consultation (beta=0.24; ( 95%CI=0.02-0.16) ease of getting
      the clinic site, short waiting time (beta=0.17; 95%CI=0.15-029) and educational
      level (beta=0.09; 95%CI =0.09-0.29) were significantly associated with overall
      satisfaction. CONCLUSIONS: The findings of this study showed that there was lack
      of critical resources for the provision of quality family planning services in
      all of the primary health care centers included in the study. This has affected
      important aspects of service provision including the use of IEC materials during
      consultations. Hence, it is advisable that health managers of the health
      facilities and the district health office ensure improved availability of trained
      personnel, IEC materials and other supplies at the clinics.

PMID- 24307825
TI  - Is plaque removal efficacy of toothbrush related to bristle flaring? A 3-month
      prospective parallel experimental study.
AB  - BACKGROUND: Toothbrushes are over-the-counter products; therefore, no special
      instruction is given to users when they purchase. There are scarce published
      studies that have investigated about how often toothbrushes should be replaced.
      Thus, this study aimed to verify the impact of the Progressive Toothbrush Bristle
      Flaring on plaque control efficacy of toothbrush. MATERIALS AND METHODS: Thirty
      six subjects were randomly selected and underwent complete oral prophylaxis 10
      days prior to the Baseline plaque recording. All subjects were provided with new
      similar toothbrushes and were divided into two groups. New Brush Group changed
      toothbrush every month and Old month Group used single toothbrush for the whole
      period of the study. Both groups were assessed for plaque accumulation every
      month using Turesky et al, (1970) modification of the Quigley and Hein (1962)
      plaque index. Toothbrush head was photographed and assessed by measuring the
      brushing surface area on standardized photographs using National Institutes of
      Health Image Analysis Program (USA). RESULTS: Both groups showed similar plaque
      scores at the 40(th) day; progressive increase in the plaque scores in group
      without changing the toothbrush were recorded at the 70(th) and 100(th) days. As
      toothbrush flaring increased, the plaque scores also increased in the Old Brush
      Group. Highest plaque accumulation was recorded in Mandibular Lingual aspects in
      Old Brush Group. CONCLUSION: Progressive increase was seen in the plaque scores
      with increase in toothbrush bristle flaring.

PMID- 24307826
TI  - Oral assessment and nursing interventions among Nigerian nurses-knowledge,
      practices and educational needs.
AB  - BACKGROUND: Assessment of oral condition, oral care, and informing the attending
      doctor of unusual oral findings for possible consultation or referral to a
      dentist are the advocated roles of hospital nurses. The objective of the study
      was thus to assess the roles of Nigerian nurses in the assessment of oral
      conditions of hospitalized patients. METHODS: This questionnaire-based cross
      sectional survey of all nurses caring for hospitalized patients in the University
      of Benin Teaching Hospital was conducted in the first half of 2010. RESULTS: Of
      the 384 studied participants, 94.3% considered oral care as an important aspect
      of nursing care and 73.4% had oral health component in their nursing school
      curriculum. A total of 80.7% reported suspicious and abnormal findings in
      hospitalized patients to the attending doctor. Amongst the respondents, 38.0%
      reported ability to conduct good oral tissue examination. Only 28.1% demonstrated
      good knowledge of common oral diseases. Three-quarters (73.4%) thought that it is
      compulsory for nurses to assess the oral condition of hospitalized patients. The
      67.7% and 21.9% of the respondents did the assessment on admission and discharge
      respectively. The majority (90.1%) desired training on oral care of hospitalized
      patients. CONCLUSION: There is a need to improve the skill and competence of
      nurses in the assessment of oral condition to make them a substantive partner in
      the oral care of hospitalized patients.

PMID- 24307827
TI  - A meta-analysis of drug resistant tuberculosis in Sub-Saharan Africa: how
      strongly associated with previous treatment and HIV co-infection?
AB  - BACKGROUND: In Sub-Saharan Africa, the fight against tuberculosis (TB) has
      encountered a great challenge because of the emergence of drug resistant TB
      strains and the high prevalence of HIV infection. The aim of this meta-analysis
      was to determine the association of drug-resistant TB with anti-TB drug treatment
      history and HIV co-infection. METHODS: After electronic based literature search
      in the databases of Medline, HINARI, EMBASE and the Cochrane library, article
      selection and data extraction were carried out. HIV co-infection and previous
      history of TB treatment were used as predictors for the occurrence of any anti-TB
      drug resistant or multiple drug resistant TB (MDR-TB). The risk ratios for each
      included study and for the pooled sample were computed using the random-effects
      model. Heterogeneity test, sensitivity analyses and funnel plots were also done.
      RESULTS: The pooled analysis showed that the risk of developing drug-resistant TB
      to at least one anti-TB drug was about 3 times higher in individuals who had a
      previous history of anti-TB treatment than new TB cases. The risk of having MDR
      TB in previously anti-TB treated TB cases was more than 5-fold higher than that
      of new TB cases. Resistance to Ethambutol and Rifampicin was more than fivefold
      higher among the previously treated with anti-TB drugs. However, HIV infection
      was not associated with drug-resistant TB. CONCLUSION: There was a strong
      association of previous anti-TB treatment with MDR-TB. Primary treatment warrants
      special emphasis, and screening for anti-TB drugs sensitivity has to be
      strengthened.

PMID- 24307828
TI  - Gender disparity in prevalence of depression among patient population: a
      systematic review.
AB  - BACKGROUND: Many people are unable to withstand the set point for usual
      vicissitudes of life and are overwhelmed by depression, especially when there is
      a potential stressor like a disease. Gender is very important in defining
      susceptibility and exposure to a number of mental health risks. The objective of
      this review is to systematically identify, appraise and synthesize the best
      available evidence on gender disparity in prevalence of depression among patient
      populations. METHODS: Observational analytical studies done on patients of 18
      years old were included. The JBI-MAStARI tool for extraction was used to pool
      quantitative data. Review Manager Software was used for meta-analysis and Odds
      ratios and their 95% confidence intervals were calculated. RESULT: On Meta
      analysis, a total of 19639 patients were involved, with male to female ratio of
      1.14:1. The finding of the Meta analysis showed that male sex is 63% less likely
      to develop depression than female sex (Odds ratio=0.63, 95% Confidence Interval=
      0.59, 0.68). The studies included were homogenous; Heterogeneity test: Chi(2) =
      309.23, df = 30, (P < 0.00001). CONCLUSION: Depression is more common among
      females than male patients.

PMID- 24307829
TI  - Non-syndromic unilateral supplemental maxillary central incisor: a case report.
AB  - BACKGROUND: Supernumerary teeth are developmental anomaly. There are various
      theories explaining their occurrence. Maxilla is more commonly affected and males
      have higher predilection than females for having supernumerary teeth. CASE
      DETAILS: The present case is presented with three permanent central incisors, all
      of them with normal morphology. On clinical and radiographic examination, it was
      identified as a case of non-syndromic unilateral left supplemental maxillary
      central incisor. Treatment plan involved extraction of the supplemental tooth
      followed by orthodontic treatment to correct the malalignment of the teeth.
      CONCLUSION: The presence of supplemental teeth of normal morphology is quite a
      rare condition and are commonly associated with various syndromes but, in rare
      cases, they also exists as non-syndromic forms. Supernumerary teeth can cause
      aesthetic or functional problems, especially when situated in the maxillary
      anterior region. Complications related to the phenomenon can be minimized by
      early detection and by carrying out a comprehensive treatment protocol.

PMID- 24307830
TI  - Peers and the Emergence of Alcohol Use: Influence and Selection Processes in
      Adolescent Friendship Networks.
AB  - This study addresses not only influence and selection of friends as sources of
      similarity in alcohol use, but also peer processes leading drinkers to be chosen
      as friends more often than non-drinkers, which increases the number of
      adolescents subject to their influence. Analyses apply a stochastic actor-based
      model to friendship networks assessed five times from 6th through 9th grades for
      50 grade cohort networks in Iowa and Pennsylvania, which include 13,214
      individuals. Results show definite influence and selection for similarity in
      alcohol use, as well as reciprocal influences between drinking and frequently
      being chosen as a friend. These findings suggest that adolescents view alcohol
      use as an attractive, high status activity and that friendships expose
      adolescents to opportunities for drinking.

PMID- 24307831
TI  - Energy-efficient pulse-coupled synchronization strategy design for wireless
      sensor networks through reduced idle listening.
AB  - Synchronization is crucial to wireless sensor networks due to their decentralized
      structure. We propose an energy-efficient pulse-coupled synchronization strategy
      to achieve this goal. The basic idea is to reduce idle listening by intentionally
      introducing a large refractory period in the sensors' cooperation. The large
      refractory period greatly reduces idle listening in each oscillation period, and
      is analytically proven to have no influence on the time to synchronization.
      Hence, it significantly reduces the total energy consumption in a synchronization
      process. A topology control approach tailored for pulse-coupled synchronization
      is given to guarantee a k-edge strongly connected interaction topology, which is
      tolerant to communication-link failures. The topology control approach is totally
      decentralized and needs no information exchange among sensors, and it is
      applicable to dynamic network topologies as well. This facilitates a completely
      decentralized implementation of the synchronization strategy. The strategy is
      applicable to mobile sensor networks, too. QualNet case studies confirm the
      effectiveness of the synchronization strategy.

PMID- 24307832
TI  - Preimmigration Family Cohesion and Drug/Alcohol Abuse Among Recent Latino
      Immigrants.
AB  - Given the growing population of Latino immigrants in the United States, it is
      critical for counselors to understand pre- and postimmigration social contextual
      factors affecting the mental health of this heterogeneous ethnic population. The
      objective of our cross-sectional, retrospective study was to investigate the
      potential protective influence of preimmigration family cohesion on drug/alcohol
      abuse just prior to migration among 527 Latino young adults (age 18-34 years).
      Multivariate Poisson regression indicated that preimmigration family cohesion was
      inversely related with harmful/hazardous alcohol consumption, the
      frequency/quantity of alcohol use, and illicit drug use when controlling for the
      potentially confounding sociodemographic factors of gender, age, education,
      income, marital status, and immigration status (documented or undocumented).
      Associations between family cohesion and drug/alcohol use behaviors varied
      between Central American immigrants and Caribbean/South American regional groups.
      Preimmigration findings offer a fuller contextual understanding of the lives of
      Latino young adult immigrants and support the importance of family cohesion as a
      buffer against drug/alcohol abuse.

PMID- 24307834
TI  - Treatment approaches and antibiotic use for emergency dental treatment in Turkey.
AB  - The purpose of this study was to gather information about Turkish general dental
      practitioners' treatment approaches towards endodontic emergencies, antibiotic
      prescribing habits, and their participation in lifelong learning programs.
      Questionnaires were given to dentists who attended the 16th National Congress
      organized by the Turkish Dental Association. From 1,400 questionnaires
      distributed, 589 (43%) were deemed usable in this study. This survey dealt with
      questions that were subdivided into two main topics: dental emergency treatment
      approaches, and antibiotic prescription and information on lifelong learning
      program participation. The statistical analysis was conducted with a chi (2) test
      at a significance level of P<0.05. For irreversible pulpitis cases in vital
      teeth, most of the dental practitioners (65.3%) preferred single-visit root canal
      treatments. For teeth presenting a periapical lesion, the preferred treatment
      approach was root canal treatment (91.5%). The rate of prescription of analgesics
      and antibiotics was 21.7% in untreated acute apical periodontitis cases and 41%
      in acute apical abscess cases. Frequently prescribed antibiotics were amoxicillin
      clavulanate (61.8%) and amoxicillin (46.5%). There was a tendency for
      practitioners to attend congresses as their years of professional practice
      increased (P<0.0001). There have been discrepancies between taught and observed
      practice. Educational initiatives are needed to prevent inappropriate
      prescription of antibiotics. 

PMID- 24307833
TI  - Guidelines for overcoming hospital managerial challenges: a systematic literature
      review.
AB  - PURPOSE: The need to respond to accreditation institutes' and patients'
      requirements and to align health care results with increased medical knowledge is
      focusing greater attention on quality in health care. Different tools and
      techniques have been adopted to measure and manage quality, but clinical errors
      are still too numerous, suggesting that traditional quality improvement systems
      are unable to deal appropriately with hospital challenges. The purpose of this
      paper is to grasp the current tools, practices, and guidelines adopted in health
      care to improve quality and patient safety and create a base for future research
      on this young subject. METHODS: A systematic literature review was carried out. A
      search of academic databases, including papers that focus not only on lean
      management, but also on clinical errors and risk reduction, yielded 47 papers.
      The general characteristics of the selected papers were analyzed, and a content
      analysis was conducted. RESULTS: A variety of managerial techniques, tools, and
      practices are being adopted in health care, and traditional methodologies have to
      be integrated with the latest ones in order to reduce errors and ensure high
      quality and patient safety. As it has been demonstrated, these tools are useful
      not only for achieving efficiency objectives, but also for providing higher
      quality and patient safety. Critical indications and guidelines for successful
      implementation of new health managerial methodologies are provided and
      synthesized in an operative scheme useful for extending and deepening knowledge
      of these issues with further studies. CONCLUSION: This research contributes to
      introducing a new theme in health care literature regarding the development of
      successful projects with both clinical risk management and health lean management
      objectives, and should address solutions for improving health care even in the
      current context of decreasing resources.

PMID- 24307835
TI  - How far has The Korean Journal of Internal Medicine advanced in terms of journal
      metrics?
AB  - The Korean Journal of Internal Medicine has already been valued as an
      international journal, according to a citation analysis in 2011. Now, 2 years
      later, I would like to confirm how much the Journal has advanced from the point
      of view of journal metrics by looking at the impact factor, cites per document (2
      years), SCImago Journal Rank (SJR), and the Hirsch index. These were obtained
      from a variety of databases, such as the Korean Medical Citation Index, KoreaMed
      Synapse, Web of Science, JCR Web, and SCImago Journal & Country Rank. The
      manually calculated 2012 impact factor was 1.252 in the Web of Science, with a
      ranking of 70/151 (46.4%) in the category of general and internal medicine. Cites
      per documents (2 years) for 2012 was 1.619, with a ranking of 267/1,588 (16.8%)
      in the category of medicine (miscellaneous). The 2012 SJR was 0.464, with a
      ranking of 348/1,588 (21.9%) in the category of medicine (miscellaneous). The
      Hirsch index from KoreaMed Synapse, Web of Science, and SCImago Journal & Country
      Rank were 12, 15, and 19, respectively. In comparison with data from 2010, the
      values of all the journal metrics increased consistently. These results reflect
      favorably on the increased competency of editors and authors of The Korean
      Journal of Internal Medicine. 

PMID- 24307836
TI  - Counteracting the enzymatic activity of dipeptidylpeptidase 4 for potential
      therapeutic advantage, with an emphasis on cord blood transplantation.
AB  - Dipeptidylpeptidase (DPP) 4, also known as CD26, is an enzyme present on the
      surface of a number of different cell types. It is also found within cells and as
      a soluble protein in body fluids. It can specifically truncate proteins at the
      penultimate N-terminus residue for some amino acids, such as alanine, proline,
      serine, and perhaps others. DPP4 has been implicated in regulating the in vitro
      and in vivo functional activities of a number of hematopoietically active
      molecules, and this information, along with that on inhibition of DPP4, has been
      studied in efforts to enhance hematopoietic cell transplantation (HCT),
      hematopoiesis after stress in mouse models, and in the clinical setting of single
      unit cord blood (CB) HCT. This article reviews the current status of this
      compound's effects on regulatory proteins, the field of CB HCT, a potential role
      for modulating DPP4 activity in enhancing single-unit CB HCT in adults, and
      future aspects in context of other cellular therapies and the area of
      regenerative medicine. 

PMID- 24307837
TI  - The role of rhinosinusitis in severe asthma.
AB  - The prevalence of asthma is approximately 5% to 10% in the general population. Of
      these, approximately 5% to 10% are severe asthmatics who respond poorly to
      asthmatic drugs, including high-dose inhaled steroids. Severe asthmatics have
      persistent symptoms, frequent symptom exacerbation, and severe airway obstruction
      even when taking high-dose inhaled steroids. The medical costs of treating severe
      asthmatics represent ~50% of the total healthcare costs for asthma. Risk factors
      for severe asthma are genetic and environmental, including many kinds of
      aeroallergens, beta-blockers, and anti-inflammatory drugs. Gastroesophageal
      reflux disease and factors such as denial, anxiety, fear, depression,
      socioeconomic status, and alcohol consumption can exacerbate asthma. Rhinitis and
      asthma usually occur together. There is increasing evidence that allergic
      rhinitis and rhinosinusitis may influence the clinical course of asthma. This
      review discusses the role of rhinosinusitis in severe asthma. 

PMID- 24307838
TI  - Is there enough support for endobronchial ultrasound-guided transbronchial needle
      aspiration as an initial diagnostic tool?

PMID- 24307839
TI  - A biomarker, osteoprotegerin, in patients undergoing hemodialysis.

PMID- 24307840
TI  - Persistent methicillin-resistant Staphylococcus aureus bacteremia: do we need a
      new therapeutic strategy?

PMID- 24307841
TI  - The diagnostic efficacy and safety of endobronchial ultrasound-guided
      transbronchial needle aspiration as an initial diagnostic tool.
AB  - BACKGROUND/AIMS: Real-time, convex probe endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) is used for the staging of malignant
      mediastinal lymph nodes. We evaluated the diagnostic efficacy and safety of EBUS
      TBNA when used as an initial diagnostic tool. METHODS: We retrospectively studied
      56 patients who underwent EBUS-TBNA as an initial diagnostic tool between August
      2010 and December 2011. Procedure purpose were classified into four categories:
      1) intrathoracic masses adjacent to the central airway; 2) enlarged lymph nodes
      for concurrent diagnosis and staging in suspected malignancy; 3) enlarged lymph
      nodes in suspected malignancy cases with inability to perform percutaneous core
      needle biopsy (PCNB); and 4) solely mediastinal masses/lymph nodes in lieu of
      mediastinoscopy. RESULTS: The diagnostic accuracy of EBUS-TBNA regardless of
      procedure purpose was calculated to be 83.9%. Furthermore, the diagnostic
      accuracy of malignant disease was significantly higher than benign disease (93.9%
      vs. 70.6%, p < 0.001). The diagnostic accuracy of EBUS-TBNA for each disease is
      as follows: tuberculosis, 50%; sarcoidosis, 60%; aspergillosis, 100%; lung
      abscess, 100%; lung cancer, 93%; and lymphoma, 100%. There were minor
      complications in seven patients during the EBUS-TBNA procedure. The complications
      included mild hypoxia and bleeding. CONCLUSIONS: In conclusion, EBUS-TBNA is a
      useful initial diagnostic tool for both benign and malignant diseases. EBUS-TBAN
      is also a very safe procedure and less invasive compared to mediastinoscopy or
      PCNB.

PMID- 24307842
TI  - Serum osteoprotegerin is associated with vascular stiffness and the onset of new
      cardiovascular events in hemodialysis patients.
AB  - BACKGROUND/AIMS: Osteoprotegerin (OPG) and fetuin-A are vascular calcification
      regulators that may be related to high cardiovascular (CV) mortality in
      hemodialysis (HD) patients. We evaluated the relationship between OPG, fetuin-A,
      and pulse wave velocity (PWV), a marker of vascular stiffness, and determined
      whether OPG and fetuin-A were independent predictors of CV events in HD patients.
      METHODS: We conducted a prospective observational study in 97 HD patients. OPG
      and fetuin-A were measured at baseline and arterial stiffness was evaluated by
      PWV. All patients were stratified into tertiles according to serum OPG levels.
      RESULTS: A significant trend was observed across increasing serum OPG
      concentration tertiles for age, HD duration, systolic blood pressure,
      cholesterol, triglycerides, and PWV. Multiple linear regression analysis revealed
      that diabetes (beta = 0.430, p = 0.000) and OPG levels (beta = 0.308, p = 0.003)
      were independently associated with PWV. The frequency of new CV events was
      significantly higher in the upper OPG tertiles compared with those in the lower
      OPG tertiles. In Cox proportional hazards analysis, upper tertiles of OPG levels
      were significantly associated with CV events (hazard ratio = 4.536, p = 0.011).
      CONCLUSIONS: Serum OPG, but not fetuin-A, levels were closely associated with
      increased vascular stiffness, and higher OPG levels may be independent predictors
      of new CV events in HD patients.

PMID- 24307843
TI  - Predictors and clinical outcomes of persistent methicillin-resistant
      Staphylococcus aureus bacteremia: a prospective observational study.
AB  - BACKGROUND/AIMS: The high mortality attributable to persistent methicillin
      resistant Staphylococcus aureus (MRSA) bacteremia in spite of glycopeptide
      treatment has heightened the need for early detection and intervention with
      alternative agents. The purpose of this study was to determine the clinical
      characteristics of and risk factors for persistent MRSA bacteremia. METHODS: All
      first episodes of significant MRSA bacteremia at a 710-bed academic medical
      center from November 2009 through August 2010 were recorded. Blood cultures were
      conducted at 3 days and every 2 to 3 days thereafter until clearance. Clinical
      characteristics and outcomes were compared between persistent MRSA bacteremia (>=
      7 days) and nonpersistent MRSA bacteremia (<= 3 days). RESULTS: Of 79 patients
      with MRSA bacteremia during the study period, 31 (39.2%) had persistent MRSA
      bacteremia. The persistent MRSA bacteremia group had significantly higher 30-day
      mortality than the nonpersistent MRSA bacteremia group (58.1% vs. 16.7%, p <
      0.001). Multivariate analysis indicated that metastatic infection at presentation
      (odds ratio [OR], 14.57; 95% confidence interval [CI], 3.52 to 60.34; p < 0.001)
      and delayed catheter removal in catheter-related infection (OR, 3.80; 95% CI,
      1.04 to 13.88; p = 0.004) were independent predictors of persistent MRSA
      bacteremia. Patients with a time to blood culture positivity (TTP) of < 11.8
      hours were at increased risk of persistent MRSA bacteremia (29.0% vs. 8.3%, p =
      0.029). CONCLUSIONS: High mortality in patients with persistent MRSA bacteremia
      was noted. Early detection of metastatic infection and early removal of infected
      intravascular catheters should be considered to reduce the risk of persistent
      MRSA bacteremia. Further studies are needed to evaluate the role of TTP for
      predicting persistent MRSA bacteremia.

PMID- 24307844
TI  - Clinicopathological characteristics of synchronous and metachronous gastric
      neoplasms after endoscopic submucosal dissection.
AB  - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has become accepted as a
      minimally invasive treatment for gastric neoplasms. However, the development of
      synchronous or metachronous gastric lesions after endoscopic resection has become
      a major problem. We investigated the characteristics of multiple gastric
      neoplasms in patients with early gastric cancer (EGC) or gastric adenoma after
      ESD. METHODS: In total, 512 patients with EGC or gastric adenoma who had
      undergone ESD between January 2008 and December 2011 participated in this study.
      The incidence of and factors associated with synchronous and metachronous gastric
      tumors were investigated in this retrospective study. RESULTS: In total, 66
      patients (12.9%) had synchronous lesions, and 13 patients (2.5%) had metachronous
      lesions. Older (> 65 years) subjects had an increased risk of multiple gastric
      neoplasms (p = 0.012). About two-thirds of the multiple lesions were similar in
      macroscopic and histological type to the primary lesions. The median interval
      from the initial lesions to the diagnosis of metachronous lesions was 31 months.
      The annual incidence rate of metachronous lesions was approximately 3%.
      CONCLUSIONS: We recommend careful follow-up in patients of advanced age (> 65
      years) after initial ESD because multiple lesions could be detected in the
      remnant stomach. Annual surveillance might aid in the detection of metachronous
      lesions. Large-scale, multicenter, and longer prospective studies of appropriate
      surveillance programs are needed.

PMID- 24307846
TI  - Meta-analysis of randomized controlled trials of bosentan for treatment of
      pulmonary arterial hypertension.
AB  - BACKGROUND/AIMS: We assessed the efficacy and safety of bosentan in patients with
      pulmonary arterial hypertension (PAH). METHODS: We surveyed randomized controlled
      trials (RCTs) of the efficacy and safety of bosentan in patients with PAH using
      MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches.
      Meta-analysis of RCTs was performed to determine treatment efficacy and safety
      outcomes. Results are presented as odds ratios (ORs) or weighted mean differences
      (WMDs). RESULTS: Meta-analysis of seven RCTs including a total of 410 patients
      and 296 controls revealed that the 6-minute work distance was significantly
      higher in the bosentan group than in the placebo group (WMD, 46.19; 95%
      confidence interval [CI], 21.20 to 71.19; p = 2.9 * 10(-5)). Compared with the
      placebo, bosentan significantly reduced the mean pulmonary arterial pressure in
      patients with PAH (WMD, -6.026; 95% CI, -8.785 to -3.268, p = 1.8 * 10(-6)). The
      bosentan therapy group worsened less clinically than the placebo group (OR,
      0.252; 95% CI, 0.140 to 0.454; p = 4.6 * 10(-7)). The incidence of serious
      adverse events did not differ between the bosentan and placebo groups (OR, 0.948;
      95% CI, 0.556 to 1.614; p = 0.843). However, the results of the abnormal liver
      function test (LFT) were significantly higher in the bosentan group than in the
      placebo group (OR, 2.312; 95% CI, 1.020 to 5.241; p = 0.045). CONCLUSIONS: This
      meta-analysis shows that bosentan can treat PAH effectively. However, bosentan
      increased the incidence of abnormal LFT results compared with the placebo.

PMID- 24307845
TI  - Endoscopic comparison of alendronate alone and the enteric-coated alendronate
      with calcitriol combination in postmenopausal Korean females.
AB  - BACKGROUND/AIMS: This study was performed to compare the mucosal findings after
      esophagogastroduodenoscopy in two groups before and after the use of alendronate
      only and following administration of the enteric-coated alendronate (5 mg) and
      calcitriol (0.5 ug) combined drug (Maxmarvil, Yuyu Co.). METHODS: The study
      population consisted of 33 postmenopausal healthy female volunteers, aged 50 to
      70 years (mean age, 58 +/- 5) without gastrointestinal symptoms and with normal
      baseline endoscopic findings. Esophagogastroduodenoscopy was performed at
      baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17
      subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were
      reported by an endoscopist after 2 weeks of treatment with each medication
      schedule. RESULTS: Esophageal mucosal injuries developed in two of 16 subjects in
      the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal
      injuries developed in eight subjects in the alendronate group and four subjects
      in the Maxmarvil group; this difference was statistically significant.
      CONCLUSIONS: The mucosal damage scores for the alendronate group (total score 24)
      were significantly higher than those for the Maxmarvil group (total score 9) in
      the esophagus and stomach. Therefore, this study suggested that enteric-coated
      Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may
      improve the tolerability of osteoporosis medication in clinical practice.

PMID- 24307847
TI  - A polymorphism in the histone deacetylase 1 gene is associated with the response
      to corticosteroids in asthmatics.
AB  - BACKGROUND/AIMS: Recent investigations suggest that histone deacetylase 1 (HDAC1)
      and HDAC2 may be target molecules to predict therapeutic responses to
      corticosteroids. We evaluated the effects of variation in HDAC1 and HDAC2 on the
      response to corticosteroids in asthmatics. METHODS: Two single nucleotide
      polymorphisms (SNPs) were selected after resequencing HDAC1 and HDAC2. For the
      first analysis, we evaluated the association between those SNPs and asthma
      severity in 477 asthmatics. For the second analysis, we evaluated the effects of
      these SNPs on lung function improvements in response to corticosteroid treatment
      in 35 independent adult asthmatics and 70 childhood asthmatics. RESULTS: We found
      that one SNP in HDAC1 (rs1741981) was significantly related to asthma severity in
      a recessive model (corrected p = 0.036). Adult asthmatics who were homozygous for
      the minor allele of rs1741981 showed significantly lower % forced expiratory
      volume in 1 second (%FEV1) increases in response to systemic corticosteroids
      treatment compared with the heterozygotes or those homozygous for the major
      allele (12.7% +/- 7.2% vs. 37.4% +/- 33.7%, p = 0.018). Similarly, childhood
      asthmatics who were homozygous for the minor allele of rs1741981 showed
      significantly lower %FEV1 increases in response to inhaled corticosteroid
      treatment compared with the heterozygotes or those homozygous for the major
      allele (14.1% +/- 5.9% vs. 19.4% +/- 8.9%, p = 0.035). CONCLUSIONS: The present
      study demonstrated that rs1741981 in HDAC1 was significantly associated with the
      response to corticosteroid treatment in asthmatics.

PMID- 24307848
TI  - Successful management of colonic perforation with a covered metal stent.
AB  - Self-expandable stents are widely available for the treatment of perforation of
      the gastrointestinal tract. Because of the risk of migration, there has been no
      report of the use of self-expandable stents for the treatment of perforation of
      the colon or rectum. This is a report of successful treatment of iatrogenic
      colonic perforation during balloon dilatation of anastomotic stricture with a
      fully covered stent. Fully covered, self-expandable metallic stents can be
      considered useful tools for management of this condition. 

PMID- 24307849
TI  - Two dislodged and crushed coronary stents: treatment of two simultaneously
      dislodged stents using crushing techniques.
AB  - Coronary stent dislodgement is a rare complication of percutaneous coronary
      intervention. We report a rare case of dislodgement of two intracoronary stents.
      On withdrawal of two balloon catheters, one with a guide wire was mechanically
      distorted from the left main (LM) to the proximal left anterior descending artery
      (LAD) while the other was dislodged from the LM to the ostial left circumflex
      artery. The stent in the LAD could not be retrieved into the guide catheter using
      a Goose neck snare, because it was caught on a previously deployed stent at the
      mid LAD. A new stent was quickly deployed from the LM to the proximal LAD,
      because the patient developed cardiogenic shock. Both stents, including a
      distorted and elongated stent, were crushed to the LM wall. Stent deployment and
      crushing may be a good alternative technique to retrieving a dislodged stent. 

PMID- 24307850
TI  - Postinfectious Guillain-Barre syndrome in a patient with methimazole-induced
      agranulocytosis.
AB  - Both Graves disease and Guillain-Barre syndrome (GBS) are autoimmune disorders
      caused by impaired self-tolerance mechanisms and triggered by interactions
      between genetic and environmental factors. GBS in patients who suffer from other
      autoimmune diseases is rarely reported, and the development of postinfectious GBS
      in a patient with Graves disease has not been previously reported in the
      literature. Herein, we report a patient with Graves disease who developed
      postinfectious GBS during a course of methimazole-induced agranulocytosis. 

PMID- 24307852
TI  - Acute regional myocarditis with normal ventricular wall motion diagnosed by two
      dimensional speckle tracking imaging.

PMID- 24307851
TI  - A case of Tsutsugamushi disease presenting with nephrotic syndrome.
AB  - Nephrotic syndrome associated with Tsutsugamushi disease has not been previously
      reported. We are describing a case of Tsutsugamuchi disease presenting with
      nephrotic syndrome. A 72-year-old woman presented with fever and generalized
      edema. Laboratory studies revealed a leukocytosis, hypoalbuminemia, and
      hypercholesterolemia. Her urine protein excretion was 5.4 g/day. The anti
      Tsutsugamushi antibody test was strongly positive (1:2,560). A renal biopsy was
      performed, and pathologic findings revealed membranous glomerulonephritis. The
      patient's clinical symptoms improved markedly after treatment with doxycycline. 

PMID- 24307853
TI  - Acute respiratory failure caused by phenytoin overdose.

PMID- 24307854
TI  - A case of primary aldosteronism presenting as non-ST elevation myocardial
      infarction.

PMID- 24307855
TI  - Penicillin G-induced hemorrhagic cystitis: a case and review of the literature.

PMID- 24307856
TI  - A giant fibroepithelial polyp mimicking a subepithelial tumor.

PMID- 24307857
TI  - Metastatic malignant solid pseudopapillary tumor of the pancreas.

PMID- 24307858
TI  - When Intuition Fails to Align with Data: A Reply to.
AB  - Holistic processing, a hallmark of face perception, is often measured in the so
      called composite paradigm, in which participants are asked to match part of a
      stimulus while ignoring another part. In prior work, we recommended against the
      use of one version of the composite task we call the partial design, on the basis
      of confounds with response biases. Rossion wrote a lengthy piece that reviews the
      work that he has published using this design, raising a large number of
      criticisms, both about an alternative measure of holistic processing that we have
      used and advocated (which we call the complete design) and about our work in
      general. In this reply, we have limited our discussion to those issues that would
      be relevant to a researcher looking to decide which version of this composite
      paradigm to use, as we doubt a comprehensive reply would be of significant
      interest outside a very small circle.

PMID- 24307859
TI  - A highly efficient nano-Fe3O4 encapsulated-silica particles bearing sulfonic acid
      groups as a solid acid catalyst for synthesis of 1,8-dioxo-octahydroxanthene
      derivatives.
AB  - ABSTRACT: The functionalization of silica-coated Fe3O4 magnetic nanoparticles
      (Fe3O4@SiO2) using chlorosulfonic acid were afforded sulfonic acid-functionalized
      magnetic Fe3O4 nanoparticles (Fe3O4@SiO2-SO3H) that can be applied as an organic
      inorganic hybrid heterogeneous catalyst. The used Fe3O4 magnetic nanoparticles
      are 18-30 nm sized that was rapidly functionalized and can be used as catalyst in
      organic synthesis. The prepared nanoparticles were characterized by X-ray
      diffraction analysis, magnetization curve, scanning electron microscope, dynamic
      laser scattering, and FT-IR measurements. The resulting immobilized catalysts
      have been successfully used in the synthesis of 1,8-dioxo-octahydroxanthene
      derivatives under solvent free condition. This procedure has many advantages such
      as; a much milder method, a shorter reaction time, a wide range of functional
      group tolerance, and absence of any tedious workup or purification. Other
      remarkable features include the catalyst can be reused at least five times
      without any obvious change in its catalytic activity. This procedure also avoids
      hazardous reagents/solvents, and thus can be an eco-friendly alternative to the
      existing methods. GRAPHICAL ABSTRACT: A highly efficient nano-Fe3O4 encapsulated
      silica particles bearing sulfonic acid groups as a solid acid catalyst for
      synthesis of 1,8-dioxo-octahydroxanthene derivatives.

PMID- 24307860
TI  - Core/shell-type nanorods of Tb3+-doped LaPO4, modified with amine groups,
      revealing reduced cytotoxicity.
AB  - ABSTRACT: A simple co-precipitation reaction between Ln3+ cations (Ln =
      lanthanide) and phosphate ions in the presence of polyethylene glycol (PEG),
      including post-treatment under hydrothermal conditions, leads to the formation of
      Tb3+-doped LaPO4 crystalline nanorods. The nanoparticles obtained can be
      successfully coated with amorphous and porous silica, forming core/shell-type
      nanorods. Both products reveal intensive green luminescence under UV lamp
      irradiation. The surface of the core/shell-type product can also be modified with
      -NH2 groups via silylation procedure, using 3-aminopropyltriethoxysilane as a
      modifier. Powder X-ray diffraction, transmission electron microscopy, and
      scanning electron microscopy confirm the desired structure and needle-like shape
      of the products synthesized. Fourier transform infrared spectroscopy and specific
      surface area measurements by Brunauer-Emmett-Teller method reveal a successful
      surface modification with amine groups of the core/shell-type nanoparticles
      prepared. The nanomaterials synthesized exhibit green luminescence characteristic
      of Tb3+ ions, as solid powders and aqueous colloids, examined by
      spectrofluorometry. The in vitro cytotoxicity studies reveal different degree
      toxicity of the products. LaPO4:Tb3+@SiO2@NH2 exhibits the smallest toxicity
      against B16F0 mouse melanoma cancer cells and human skin microvascular
      endothelial cell lines, in contrast to the most toxic LaPO4:Tb3+@SiO2. GRAPHICAL
      ABSTRACT: 

PMID- 24307861
TI  - Stability of silver nanoparticle monolayers determined by in situ streaming
      potential measurements.
AB  - ABSTRACT: A silver particle suspension obtained by a chemical reduction was used
      in this work. Monolayers of these particles (average size 28 nm) on mica modified
      by poly(allylamine hydrochloride) were produced under diffusion-controlled
      transport. Monolayer coverages, quantitatively determined by atomic force
      microscopy (AFM) and SEM, was regulated by adjusting the nanoparticle deposition
      time and the suspension concentration. The zeta potential of the monolayers was
      determined by streaming potential measurements carried out under in situ (wet)
      conditions. These measurements performed for various ionic strengths and pH were
      interpreted in terms of the three-dimensional (3D) electrokinetic model. The
      stability of silver monolayers was also investigated using streaming potential
      and the AFM methods. The decrease in the surface coverage of particles as a
      function of time and ionic strength varied between 10-1 and 10-4 M was
      investigated. This allowed one to determine the equilibrium adsorption constant
      Ka and the binding energy of silver particles (energy minima depth). Energy
      minima depth were calculated that varied between -18 kT for I = 10-1 M and -19 kT
      for I = 10-4 for pH 5.5 and T = 298 K. Our investigations suggest that the
      interactions between surface and nanoparticles are controlled by the
      electrostatic interactions among ion pairs. It was also shown that the in situ
      electrokinetic measurements are in accordance with those obtained by more tedious
      ex situ AFM measurements. This confirmed the utility of the streaming potential
      method for direct kinetic studies of nanoparticle deposition/release processes.
      GRAPHICAL ABSTRACT: 

PMID- 24307862
TI  - Functionalized NaA nanozeolites labeled with 224,225Ra for targeted alpha
      therapy.
AB  - The 223Ra, 224Ra, and 225Ra radioisotopes exhibit very attractive nuclear
      properties for application in radionuclide therapy. Unfortunately the lack of
      appropriate bifunctional ligand for radium is the reason why these radionuclides
      have not found application in receptor-targeted therapy. In the present work, the
      potential usefulness of the NaA nanozeolite as a carrier for radium radionuclides
      has been studied. 224Ra and 225Ra, alpha-particle emitting radionuclides, have
      been absorbed in the nanometer-sized NaA zeolite (30-70 nm) through simple ion
      exchange. 224,225Ra-nanozeolites exhibited very high stability in solutions
      containing physiological salt, EDTA, amino acids, and human serum. To make NaA
      nanozeolite particles dispersed in water their surface was modified with a silane
      coupling agent containing poly(ethylene glycol) molecules. This functionalization
      approach let us covalently attach a biomolecule to the NaA nanozeolite surface.

PMID- 24307863
TI  - AlCl3-Promoted Facile E-to-Z Isomerization Route to (Z)-2-Methyl-1-buten-1,4
      ylidene Synthons for Highly Efficient and Selective (Z)-Isoprenoid Synthesis.
AB  - Zr-catalyzed methylalumination of 3-butyn-1-ols followed by AlCl3-promoted
      stereoisomerization at 50  degrees C for 6 h provides 4-iodo-3-methyl-3-buten-1
      ols 2b and 6 of >=98 Z configuration in 87 and 67% yields, respectively. (Z)-1,4
      Diiodo-2-methyl-1-butene (1b) obtainable by iodination of 2b is a valuable
      synthon for efficient and selective syntheses of (Z)-alkene containing
      isoprenoids.

PMID- 24307864
TI  - Length Dependent Helix-Coil Transition Kinetics of Nine Alanine-Based Peptides.
AB  - It is well-known that end caps and the peptide length can dramatically influence
      the thermodynamics of the helix-coil transition. However, their roles in
      determining the kinetics of the helix-coil transition have not been studied
      extensively and are less well understood. Kinetic Ising models and sequential
      kinetic models involving barrier crossing via diffusion all predict that the
      helix formation time depends monotonically on the peptide length with the
      relaxation time increasing with respect to increasing chain length. Here, we have
      studied the helix-coil transition kinetics of a series of Ala-based alpha-helical
      peptides of different length (19-39 residues), with and without end caps, using
      time-resolved infrared spectroscopy coupled with laser-induced temperature jump
      (T-jump) initiation method. The helical content of these peptides was kinetically
      monitored by probing the amide carbonyl stretching frequencies (i.e., the amide
      I' band) of the peptide backbone. We found that the relaxation rates for peptides
      with efficient end caps are more rapid than those of the corresponding peptides
      without good end caps. These results indicate that efficient end-capping
      sequences can not only stabilize preexisting helices but also promote helix
      formation through initiation. Furthermore, we found that the relaxation times of
      these peptides, following a T-jump of 1-11  degrees C, show rather complex
      behaviors as a function of the peptide length, in disagreement with theoretical
      predications. Theses results are not readily explained by theories in which Ala
      is taken to have a single helical propensity (s). However, recent studies have
      suggested that s depends on chain length; when this factor is considered, the
      mean first-passage times of the coil-to-helix transition show similar dependence
      on the peptide length as those observed experimentally.

PMID- 24307865
TI  - The Influence of Religious Coping on the Acculturative Stress of Recent Latino
      Immigrants.
AB  - Acculturative stress negatively impacts the physical and mental health of Latino
      immigrants. Little is known about the pre-immigration resources that may
      influence the acculturative stress of Latino immigrants. Religion plays a
      prominent role in Latino culture and may prove to be an influential resource
      during difficult life transitions, such as those experienced during the
      immigration process. The present study examines the association between religious
      coping resources prior to immigration and acculturative stress after immigration
      within a multiethnic sample of 527 adult Latinos who have lived in the United
      States for less than 1 year. Path analyses revealed that pre-immigration external
      religious coping was associated with high levels of post-immigration
      acculturative stress. Illegal immigrant status was associated with high levels of
      pre-immigration religious coping as well as post-immigration acculturative
      stress. These findings expand scientific understanding as to the function and
      effect of specific religious coping mechanisms among Latino immigrants.
      Furthermore, results underscore the need for future research, which could serve
      to inform culturally relevant prevention and treatment programs.

PMID- 24307867
TI  - Testing normal means: the reconcilability of the P value and the Bayesian
      evidence.
AB  - The problem of reconciling the frequentist and Bayesian evidence in testing
      statistical hypotheses has been extensively studied in the literature. Most of
      the existing work considers cases without the nuisance parameters which is not
      the frequently encountered situation since the presence of the nuisance
      parameters is very common in practice. In this paper, we consider the
      reconcilability of the Bayesian evidence against the null hypothesis H0 in terms
      of the posterior probability of H0 being true and the frequentist evidence
      against H0 in terms of the P value in testing normal means where the nuisance
      parameters are present. The reconcilability of evidence can be obtained both for
      testing a normal mean and for the Behrens-Fisher problem.

PMID- 24307866
TI  - Alkyne-azide cycloaddition catalyzed by silver chloride and "abnormal" silver N
      heterocyclic carbene complex.
AB  - A library of 1,2,3-triazoles was synthesized from diverse alkynes and azides
      using catalytic amounts of silver chloride instead of copper compounds. In
      addition, a novel "abnormal" silver N-heterocyclic carbene complex was tested as
      catalyst in this process. The results suggest that the reaction requires only
      0.5% of silver complex, affording 1,2,3-triazoles in good yields. 

PMID- 24307868
TI  - Synthesis, characterization and application of 1-butyl-3 methylimidazolium
      chloride as green material for extractive desulfurization of liquid fuel.
AB  - The possible application of imidazolium ionic liquids as energy-efficient green
      material for extractive deep desulfurization of liquid fuel has been
      investigated. 1-Butyl-3-methylimidazolium chloride [BMIM]Cl was synthesized by
      nucleophilic substitution reaction of n-methylimidazolium and 1-chlorobutane.
      Molecular structures of the ILs were confirmed by FTIR, (1)H-NMR, and (13)C-NMR.
      The thermal properties, conductivity, solubility, water content and viscosity
      analysis of [BMIM]Cl were carried out. The effects of reaction time, reaction
      temperature, sulfur compounds, and recycling of IL without regeneration on
      dibenzothiophene removal of liquid fuel were presented. In the extractive
      desulfurization process, the removal of dibenzothiophene in n-dodecane using
      [BMIM]Cl was 81% with mass ratio of 1 : 1, in 30 min at 30 degrees C under the
      mild reaction conditions. Also, desulfurization of real fuels with IL and
      multistage extraction were studied. The results of this work might offer
      significant insights in the perceptive use of imidazoled ILs as energy-efficient
      green material for extractive deep desulfurization of liquid fuels as it can be
      reused without regeneration with considerable extraction efficiency.

PMID- 24307869
TI  - Germination response of MR 219 rice variety to different exposure times and
      periods of 2450 MHz microwave frequency.
AB  - Germination is a key process in plants' phenological cycles. Accelerating this
      process could lead to improvment of the seedling growth as well as the
      cultivation efficiency. To achieve this, the effect of microwave frequency on the
      germination of rice seeds was examined. The physiological feedbacks of the MR 219
      rice variety in terms of seed germination rate (GR), germination percentage (GP),
      and mean germination time (MGT) were analyzed by exposing its seeds to 2450 MHz
      of microwave frequency for one, four, seven, and ten hours. It was revealed that
      exposing the seeds to the microwave frequency for 10 hours resulted in the
      highest GP. This treatment led to 100% of germination after three days with a
      mean germination time of 2.1 days. Although the other exposure times of microwave
      frequency caused the moderate effects on germination with a GP(a3) ranged from
      93% to 98%, they failed to reduce the MGT(a3). The results showed that ten-hour
      exposure times of microwave frequency for six days significantly facilitated and
      improved the germination indices (primary shoot and root length). Therefore, the
      technique is expected to benefit the improvement of rice seed germination
      considering its simplicity and efficacy in increasing the germination percentage
      and rate as well as the primary shoot and root length without causing any
      environmental toxicity.

PMID- 24307870
TI  - Magnetohydrodynamic simulations of hypersonic flow over a cylinder using axial-
      and transverse-oriented magnetic dipoles.
AB  - Numerical simulations of magnetohydrodynamic (MHD) hypersonic flow over a
      cylinder are presented for axial- and transverse-oriented dipoles with different
      strengths. ANSYS CFX is used to carry out calculations for steady, laminar flows
      at a Mach number of 6.1, with a model for electrical conductivity as a function
      of temperature and pressure. The low magnetic Reynolds number (<<1) calculated
      based on the velocity and length scales in this problem justifies the quasistatic
      approximation, which assumes negligible effect of velocity on magnetic fields.
      Therefore, the governing equations employed in the simulations are the
      compressible Navier-Stokes and the energy equations with MHD-related source terms
      such as Lorentz force and Joule dissipation. The results demonstrate the ability
      of the magnetic field to affect the flowfield around the cylinder, which results
      in an increase in shock stand-off distance and reduction in overall temperature.
      Also, it is observed that there is a noticeable decrease in drag with the
      addition of the magnetic field.

PMID- 24307871
TI  - Carpal tunnel release surgery and venous hypertension in early hemodialysis
      patients without amyloid deposits.
AB  - AIM: Carpal tunnel syndrome (CTS) is one of the frequent problems of the patients
      who underwent hemodialysis (HD). The role of venous hypertension due to
      arteriovenous fistula (AVF) has not been clarified completely; therefore, we
      aimed to investigate the role of venous hypertension due to AVF in hemodialysis
      patients who had CTS. PATIENTS AND METHODS: We included 12 patients who had been
      receiving HD treatment for less than 8 years and the newly diagnosed CTS patients
      with the same arm of AVF. All patients were diagnosed clinically and the results
      were confirmed by both nerve conduction studies and electromyography. Open carpal
      tunnel release surgery was performed on all of them. Venous pressure was measured
      in all patients before and after two weeks of surgery. RESULTS: There were
      significant differences before and after the surgery with regard to pressures (P
      > 0.05). After the surgery, all carpal ligament specimens of the patients were
      not stained with Congo red for the presence of amyloid deposition. CONCLUSION:
      Increased venous pressure on the same arm with AVF could be responsible for CTS
      in hemodialysis patients. Carpal tunnel release surgery is the main treatment of
      this disease by reducing the compression on the nerve.

PMID- 24307872
TI  - Climatic trends in hail precipitation in France: spatial, altitudinal, and
      temporal variability.
AB  - Hail precipitation is characterized by enhanced spatial and temporal variability.
      Association Nationale d'Etude et de Lutte contre les Fleaux Atmospheriques
      (ANELFA) installed hailpad networks in the Atlantic and Midi-Pyrenees regions of
      France. Historical data of hail variables from 1990 to 2010 were used to
      characterize variability. A total of 443 stations with continuous records were
      chosen to obtain a first approximation of areas most affected by hail. The
      Cressman method was selected for this purpose. It was possible to find
      relationships between spatial distributions of the variables, which are supported
      by obtained Pearson correlations. Monthly and annual trends were examined using
      the Mann-Kendall test for each of the total affected hailpads. There were 154
      pads with a positive trend; most were located between Tarbes and Saint-Gaudens.
      We found 177 pads with a negative trend, which were largely south of a pine
      forest in Landes. The remainder of the study area showed an elevated spatial
      variability with no pattern, even between relatively close hailpads. A similar
      pattern was found in Lerida (Spain) and Southeast France. In the entire area,
      monthly trends were predominantly negative in June, July, and August, whereas May
      had a positive trend; again, however, there was no spatial pattern. There was a
      high concentration of hailpads with positive trend near the Pyrenees, probably
      owing to orographic effects, and if we apply cluster analysis with the Mann
      Kendall values, the spatial variability is accentuated for stations at higher
      altitude. 

PMID- 24307873
TI  - Theoretical prediction of ultrasound elastography for detection of early
      osteoarthritis.
AB  - Ultrasound elastography could be used as a new noninvasive technique for
      detecting early osteoarthritis. As the first critical step, this study
      theoretically predicted the excitation power and the measurement errors in
      detecting cartilage detect. A finite element model was used to simulate wave
      propagation of elastography in the cartilage. The wave was produced by a force F,
      and the wave speed C was calculated. The normal cartilage model was used to
      define the relationship between the wave speed and elastic modulus. Various
      stiffness values were simulated. F = 10 N with a duration of 0.5 ms was required
      for having measurable deformation (10 MUm) at the distal site. The deformation
      had a significant rise when the wave crossed the defect. The relationship between
      the wave speed and elastic parameters was found as C = 1.57 * (E)/(2 *
      rho(1+MU)))(1/2), where E was the elastic modulus, MU was Poisson's ratio, and
      rho was the density. For the simulated defect with an elastic modulus of 7 MPa
      which was slightly stiffer than the normal cartilage, the measurement error was
      0.1 MPa. The results suggested that, given the simulated conditions, this new
      technique could be used to detect the defect in early osteoarthritis.

PMID- 24307875
TI  - Tyrosinase inhibitory effect and antioxidative activities of fermented and
      ethanol extracts of Rhodiola rosea and Lonicera japonica.
AB  - This is the first study to investigate the biological activities of fermented
      extracts of Rhodiola rosea L. (Crassulaceae) and Lonicera japonica Thunb.
      (Caprifoliaceae). Alcaligenes piechaudii CC-ESB2 fermented and ethanol extracts
      of Rhodiola rosea and Lonicera japonica were prepared and the antioxidative
      activities of different concentrations of samples were evaluated using in vitro
      antioxidative assays. Tyrosinase inhibition was determined by using the
      dopachrome method with L-DOPA as substrate. The results demonstrated that
      inhibitory effects (ED50 values) on mushroom tyrosinase of fermented Rhodiola
      rosea, fermented Lonicera japonica, ethanol extract of Lonicera japonica, and
      ethanol extract of Rhodiola rosea were 0.78, 4.07, 6.93, and >10 mg/ml,
      respectively. The DPPH scavenging effects of fermented Rhodiola rosea (ED50 =
      0.073 mg/ml) and fermented Lonicera japonica (ED50 = 0.207 mg/ml) were stronger
      than effects of their respective ethanol extracts. Furthermore, the scavenging
      effect increases with the presence of high content of total phenol. However, the
      superoxide scavenging effects of fermented Rhodiola rosea was less than effects
      of fermented Lonicera japonica. The results indicated that fermentation of
      Rhodiola rosea and Lonicera japonica can be considered as an effective
      biochemical process for application in food, drug, and cosmetics.

PMID- 24307874
TI  - Molecular dynamic simulation to explore the molecular basis of Btk-PH domain
      interaction with Ins(1,3,4,5)P4.
AB  - Bruton's tyrosine kinase contains a pleckstrin homology domain, and it
      specifically binds inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), which is
      involved in the maturation of B cells. In this paper, we studied 12 systems
      including the wild type and 11 mutants, K12R, S14F, K19E, R28C/H, E41K, L11P,
      F25S, Y40N, and K12R-R28C/H, to investigate any change in the ligand binding site
      of each mutant. Molecular dynamics simulations combined with the method of
      molecular mechanics/Poisson-Boltzmann solvent-accessible surface area have been
      applied to the twelve systems, and reasonable mutant structures and their binding
      free energies have been obtained as criteria in the final classification. As a
      result, five structures, K12R, K19E, R28C/H, and E41K mutants, were classified as
      "functional mutations," whereas L11P, S14F, F25S, and Y40N were grouped into
      "folding mutations." This rigorous study of the binding affinity of each of the
      mutants and their classification provides some new insights into the biological
      function of the Btk-PH domain and related mutation-causing diseases. 

PMID- 24307876
TI  - Aerobic exercise improves signs of restless leg syndrome in end stage renal
      disease patients suffering chronic hemodialysis.
AB  - BACKGROUND: Restless leg syndrome (RLS) is one of the prevalent complaints of
      patients with end stage renal diseases suffering chronic hemodialysis. Although
      there are some known pharmacological managements for this syndrome, the adverse
      effect of drugs causes a limitation for using them. In this randomized clinical
      trial we aimed to find a nonpharmacological way to improve signs of restless leg
      syndrome and patients' quality of life. MATERIAL AND METHODS: Twenty-six patients
      were included in the study and divided into 2 groups of control and exercise. The
      exercise group used aerobic exercise during their hemodialysis for 16 weeks. The
      quality of life and severity of restless leg syndrome were assessed at the first
      week of study and final week. Data were analyzed using SPSS software. RESULTS:
      The difference of means of RLS signs at the first week of study and final week
      was -5.5 +/- 4.96 in exercise group and -0.53 +/- 2.3 in control group. There was
      not any statistical difference between control group and exercise group in
      quality of life at the first week of study and final week. CONCLUSIONS: We
      suggest using aerobic exercise for improving signs of restless leg syndrome, but
      no evidence was found for its efficacy on patient's quality of life.

PMID- 24307877
TI  - Left prefrontal activity reflects the ability of vicarious fear learning: a
      functional near-infrared spectroscopy study.
AB  - Fear could be acquired indirectly via social observation. However, it remains
      unclear which cortical substrate activities are involved in vicarious fear
      transmission. The present study was to examine empathy-related processes during
      fear learning by-proxy and to examine the activation of prefrontal cortex by
      using functional near-infrared spectroscopy. We simultaneously measured
      participants' hemodynamic responses and skin conductance responses when they were
      exposed to a movie. In this movie, a demonstrator (i.e., another human being) was
      receiving a classical fear conditioning. A neutral colored square paired with
      shocks (CS(shock)) and another colored square paired with no shocks (CS(no
      shock)) were randomly presented in front of the demonstrator. Results showed that
      increased concentration of oxygenated hemoglobin in left prefrontal cortex was
      observed when participants watched a demonstrator seeing CS(shock) compared with
      that exposed to CS(no-shock). In addition, enhanced skin conductance responses
      showing a demonstrator's aversive experience during learning object-fear
      association were observed. The present study suggests that left prefrontal
      cortex, which may reflect speculation of others' mental state, is associated with
      social fear transmission.

PMID- 24307878
TI  - Optimizing available phosphorus in calcareous soils fertilized with diammonium
      phosphate and phosphoric acid using Freundlich adsorption isotherm.
AB  - In calcareous soils, phosphorus (P) retention and immobilization take place due
      to precipitation and adsorption. Since soil pH is considered a major soil
      variable affecting the P sorption, an acidic P fertilizer could result in low P
      adsorption compared to alkaline one. Therefore, P adsorption from DAP and
      phosphoric acid (PA) required to produce desired soil solution P concentration
      was estimated using Freundlich sorption isotherms. Two soils from Faisalabad and
      T. T. Singh districts were spiked with 0, 10, and 20 % CaCO3 for 15 days.
      Freundlich adsorption isotherms (P = aC(b/a)) were constructed, and theoretical
      doses of PA and DAP to develop a desired soil solution P level (i.e., 0.20 mg L(
      1)) were calculated. It was observed that P adsorption in soil increased with
      CaCO3. Moreover, at all the levels of CaCO3, P adsorption from PA was lower
      compared to that from DAP in both the soils. Consequently, lesser quantity of PA
      was required to produce desired solution P, 0.2 mg L(-1), compared to DAP.
      However, extrapolating the developed relationship between soil CaCO3 contents and
      quantity of fertilizer to other similar textured soils needs confirmation.

PMID- 24307879
TI  - Actinomycetes diversity among rRNA gene clones and cellular isolates from Sambhar
      salt lake, India.
AB  - The vertical stratification of actinomycetes diversity in Sambhar salt lake
      (India's largest salt lake) was investigated by using cultivable and uncultivable
      approaches. The isolates from cultured approaches were clustered on the basis of
      cultural, morphological, biochemical, and cell wall characteristics, and results
      were further strengthened by 16S rDNA-RFLP into five major groups. 16S rDNA
      sequencing of the representative isolates from each clusters was identified as
      belonging to Streptomyces, Actinopolyspora, Microbispora, Saccharopolyspora, and
      Actinoplanes genera, while culture independent group was established as
      Streptomyces (130 clones, 20 OTUs), Micromonospora (96 clones, 7 OTUs),
      Streptosporangium (79 clones, 9 OTUs), Thermomonospora (46 clones, 8 OTUs), and
      Dactylosporangium (58 clones, 8 OTUs). The diversity assessment using Shannon and
      Wiener index was found to be 1.55, 1.52, 1.55, and 1.49 from surface lake water,
      at depth of 1.5 m, shallow layer of water with algal population, and finally at
      depth of 2.5 m, respectively. We observed diversity in terms of the species
      richness as Streptomyces is dominant genus in both culture dependent and culture
      independent techniques followed by Microbispora (culture dependent methods) and
      Micromonospora (culture independent method) genera, respectively.

PMID- 24307880
TI  - Amplify-and-forward cooperative diversity for green UWB-based WBSNs.
AB  - This paper proposes a novel green cooperative diversity technique based on
      suboptimal template-based ultra-wideband (UWB) wireless body sensor networks
      (WBSNs) using amplify-and-forward (AF) relays. In addition, it analyzes the bit
      error-rate (BER) performance of the proposed nodes. The analysis is based on the
      moment-generating function (MGF) of the total signal-to-noise ratio (SNR) at the
      destination. It also provides an approximate value for the total SNR. The
      analysis studies the performance of equally correlated binary pulse position
      modulation (EC-BPPM) assuming the sinusoidal and square suboptimal template
      pulses. Numerical results are provided for the performance evaluation of optimal
      and suboptimal template-based nodes with and without relay cooperation. Results
      show that one relay node provides ~23 dB performance enhancement at 1e - 3 BER,
      which mitigates the effect of the nondesirable non-line-of-sight (NLOS) links in
      WBSNs.

PMID- 24307881
TI  - Investigation of vortex clouds and droplet sizes in heated water spray patterns
      generated by axisymmetric full cone nozzles.
AB  - The hot water sprays are an important part of many industrial processes, where
      the detailed knowledge of physical phenomena involved in jet transportation,
      interaction, secondary breakup, evaporation, and coalescence of droplets is
      important to reach more efficient processes. The objective of the work was to
      study the water spray jet breakup dynamics, vortex cloud formation, and droplet
      size distribution under varying temperature and load pressure. Using a high speed
      camera, the spray patterns generated by axisymmetric full cone nozzles were
      visualized as a function water temperature and load pressure. The image analysis
      confirmed that the spray cone angle and width do not vary significantly with
      increasing Reynolds and Weber numbers at early injection phases leading to
      increased macroscopic spray propagation. The formation and decay of semitorus
      like vortex clouds were also noticed in spray structures generated at near water
      boiling point temperature. For the nozzle with smallest orifice diameter (1.19
      mm), these vortex clouds were very clear at 90 degrees C heating temperature and
      1 bar water load pressure. In addition, the sauter mean diameter (SMD) of the
      spray droplets was also measured by using Phase Doppler Anemometry (PDA) at
      different locations downstream of the nozzle exit. It was noticed that SMD varies
      slightly w.r.t. position when measured at room temperature whereas at higher
      temperature values, it became almost constant at distance of 55 mm downstream of
      the nozzle exit.

PMID- 24307882
TI  - Some new inequalities of Jordan type for sine.
AB  - The authors find some new inequalities of Jordan type for the sine function.
      These newly established inequalities are of new form and are applied to deduce
      some known results. 

PMID- 24307883
TI  - Poly(lactic acid) filled with cassava starch-g-soybean oil maleate.
AB  - Poly(lactic acid), PLA, is a biodegradable polymer, but its applications are
      limited by its high cost and relatively poorer properties when compared to
      petroleum-based plastics. The addition of starch powder into PLA is one of the
      most promising efforts because starch is an abundant and cheap biopolymer.
      However, the challenge is the major problem associated with poor interfacial
      adhesion between the hydrophilic starch granules and the hydrophobic PLA, leading
      to poorer mechanical properties. In this paper, soybean oil maleate (SOMA) was
      synthesized by grafting soybean oil with various weight percents of maleic
      anhydride (MA) using dicumyl peroxide (DCP) as an initiator. Then, SOMA was
      employed for the surface modifying of cassava starch powder, resulting in SOMA-g
      STARCH. The obtained SOMA-g-STARCH was mixed with PLA in various weight ratios
      using twin-screw extruder, resulting in PLA/SOMA-g-STARCH. Finally, the obtained
      PLA/SOMA-g-STARCH composites were prepared by a compression molding machines. The
      compatibility, thermal properties, morphology properties, and mechanical
      properties were characterized and evaluated. The results showed that the
      compatibility, surface appearance, and mechanical properties at 90 : 10 and 80 :
      20 ratios of PLA/SOMA-g-STARCH were the best.

PMID- 24307885
TI  - Nonuniform exponential dichotomies in terms of Lyapunov functions for
      noninvertible linear discrete-time systems.
AB  - The aim of this paper is to give characterizations in terms of Lyapunov functions
      for nonuniform exponential dichotomies of nonautonomous and noninvertible
      discrete-time systems. 

PMID- 24307886
TI  - Pd(II) and Zn(II) based complexes with Schiff base ligands: synthesis,
      characterization, luminescence, and antibacterial and catalytic activities.
AB  - Two new metal complexes involving Schiff base ligands, namely, [Pd(L1)2] (1) and
      [Zn(L2)2] (2), [HL1: 2,4-dibromo-6-((E)-(mesitylimino)methyl)phenol and HL2: 2
      ((E)-(2,6-diisopropylphenylimino)methyl)-4,6-dibromophenol], have been
      solvothermally synthesized and characterized by elemental analysis, IR
      spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and single
      crystal X-ray diffraction. Both 1 and 2 are mononuclear cyclometalated complexes
      with square planar and tetrahedral coordination geometry, respectively. 1 and 2
      display photoluminescence in the solid state at 298 K (fluorescence lifetimes tau
      = 5.521 MUs at 508 nm for 1; tau = 3.697 MUs at 506 nm for 2). These Schiff base
      ligands and their metal complexes have been screened for antibacterial activity
      against several bacteria strains, and the results are compared with the activity
      of penicillin. Moreover, the Suzuki reaction of 4-bromoanisole with phenylboronic
      acid by 1 has also been studied.

PMID- 24307887
TI  - ergm.userterms: A Template Package for Extending statnet.
AB  - Exponential-family random graph models (ERGMs) represent a powerful and flexible
      class of models for the statistical analysis of networks. statnet is a suite of
      software packages that implement these models. This paper details how the
      capabilities for ERGM modeling can be expanded and customized by programming
      additional network statistics that may be included in ERGMs. We describe a
      template R package called ergm.userterms that can be modified for this purpose.
      It is designed to make this process as straightforward as possible. We also
      explain some of the internal workings of statnet that will help users develop
      their own network analysis capabilities.

PMID- 24307884
TI  - The role of TNF-alpha and TNF superfamily members in the pathogenesis of calcific
      aortic valvular disease.
AB  - Calcific aortic valve disease (CAVD) represents a slowly progressive pathologic
      process associated with major morbidity and mortality. The process is
      characterized by multiple steps: inflammation, fibrosis, and calcification.
      Numerous studies focalized on its physiopathology highlighting different "actors"
      for the multiple "acts." This paper focuses on the role of the tumor necrosis
      factor superfamily (TNFSF) members in the pathogenesis of CAVD. In particular, we
      discuss the clinical and experimental studies providing evidence of the
      involvement of tumor necrosis factor-alpha (TNF-alpha), receptor activator of
      nuclear factor-kappa B (NF-kappaB) ligand (RANKL), its membrane receptor RANK and
      its decoy receptor osteoprotegerin (OPG), and TNF-related apoptosis-inducing
      ligand (TRAIL) in valvular calcification.

PMID- 24307889
TI  - Antifungal Compounds from Piper Species.
AB  - This review documents chemical structures and antifungal activities of 68
      compounds isolated from 22 Piper species of the plant family Piperaceae. These
      compounds include amides, flavonoids, prenylated benzoic acid derivatives,
      lignans, phenylpropanoids, butenolides, and cyclopentendiones. Some of them may
      serve as leads for potential pharmaceutical or agricultural fungicide
      development.

PMID- 24307888
TI  - Honokiol as a Radiosensitizing Agent for Colorectal cancers.
AB  - Radioresistance is a frustrating obstacle for patients with colorectal cancers
      (CRCs) undergoing radiotherapy. There is an urgent need to find an effective
      agent to increase the sensitivity of CRCs to radiation. Honokiol, an active
      compound purified from Magnolia, was found to radiosensitize colorectal cancer
      cells both in vitro and in vivo. However, the mechanisms control important
      signaling that enhances radiosensitivity is currently unknown. In this study, we
      have reviewed important signaling pathways that are closely related to
      radiosensitization, such as cell cycle arrest, tumor angiogenesis, JAK/STAT3
      signaling pathway and Mismatch repair. Studies show that honokiol can interfere
      with these pathways at different levels. With overall analysis, it may bring
      light on finding the possible mechanism by which honokiol acts as a
      radiosensitizing agent for CRCs.

PMID- 24307890
TI  - Contrast improvement in sub- and ultraharmonic ultrasound contrast imaging by
      combining several hammerstein models.
AB  - Sub- and ultraharmonic (SUH) ultrasound contrast imaging is an alternative
      modality to the second harmonic imaging, since, in specific conditions it could
      produce high quality echographic images. This modality enables the contrast
      enhancement of echographic images by using SUH present in the contrast agent
      response but absent from the nonperfused tissue. For a better access to the
      components generated by the ultrasound contrast agents, nonlinear techniques
      based on Hammerstein model are preferred. As the major limitation of Hammerstein
      model is its capacity of modeling harmonic components only, in this work we
      propose two methods allowing to model SUH. These new methods use several
      Hammerstein models to identify contrast agent signals having SUH components and
      to separate these components from harmonic components. The application of the
      proposed methods for modeling simulated contrast agent signals shows their
      efficiency in modeling these signals and in separating SUH components. The
      achieved gain with respect to the standard Hammerstein model was 26.8 dB and 22.8
      dB for the two proposed methods, respectively. 

PMID- 24307891
TI  - Trends and Factors Affecting Hospitalization Costs in Patients with Inflammatory
      Bowel Disease: A Two-Center Study over the Past Decade.
AB  - With the growing number of patients with inflammatory bowel disease (IBD) and
      hospitalization cases, the overall medical care cost elevates significantly in
      consequence. A total of 2458 hospitalizations, involving 1401 patients with IBD,
      were included from two large medical centers. Hospitalization costs and factors
      impacting cost changes were determined. Patients with IBD and frequency of
      hospitalizations increased significantly from 2003 to 2011 (P < 0.001). The
      annual hospitalization cost per patient, cost per hospitalization, and daily cost
      during hospitalization increased significantly in the past decade (all P <
      0.001). However, length of stay decreased significantly (P < 0.001). Infliximab
      was the most significant factor associated with higher hospitalization cost (OR =
      44380.09, P < 0.001). Length of stay (OR = 1.29, P < 0.001), no medical insurance
      (OR = 1.31, P = 0.017), CD (OR = 3.55, P < 0.001), inflammatory bowel disease
      unclassified (IBDU) (OR = 4.30, P < 0.0001), poor prognosis (OR = 6.78, P <
      0.001), surgery (OR = 3.16, P < 0.001), and endoscopy (OR = 2.44, P < 0.001) were
      found to be predictors of higher hospitalization costs. Patients with IBD and
      frequency of hospitalizations increased over the past decade. CD patients
      displayed a special one peak for age at diagnosis, which was different from UC
      patients. The increased hospitalization costs of IBD patients may be associated
      with infliximab, length of stay, medical insurance, subtypes of IBD, prognosis,
      surgery, and endoscopy. 

PMID- 24307893
TI  - Study of RNA Interference Targeting NET-1 Combination with Sorafenib for
      Hepatocellular Carcinoma Therapy In Vitro and In Vivo.
AB  - The aim of this study is to explore the inhibitory effects of RNA interference
      (RNAi) targeting NET-1 or combined with sorafenib on HCC in vitro and in vivo and
      the possible underlying mechanisms. The expressions of NET-1 mRNA and protein
      were detected by RT-QPCR and western blot. The ability of proliferation was
      determined by CCK-8 assay. Apoptosis was examined by flow cytometry (FCM).
      Abilities of migration and invasion were measured by scratch-wound assay and
      transwell assay. MHCC97H cells with stable transfection of NET-1shRNA were
      injected subcutaneously to prepare nude mice model of HCC and Caspase-3, Caspase
      8, and Caspase-9 mRNAs of tumor tissues in different groups were examined. NET-1
      mRNA and protein were reduced sharply in MHCC97H cells transfected with NET
      1shRNA. The abilities of proliferation and migration were inhibited and apoptosis
      was promoted in either NET-1shRNA or sorafenib as compared with untreated cells
      in vitro and in vivo (P < 0.05). The mRNA levels of caspase-3, caspase-8, and
      caspase-9 of tumor tissues were reduced in different treatment groups compared
      with untreated group, particularly in combination group. (P < 0.05). The
      combination NET-1shRNA with sorafenib dramatically enhanced the effects of
      sorafenib antitumor ,which may involve in blocking ras signaling pathway and
      stimulating apoptotic pathways simultaneously. 

PMID- 24307892
TI  - PP2A-Mediated Anticancer Therapy.
AB  - PP2A is a family of mammalian serine/threonine phosphatases that is involved in
      the control of many cellular functions including protein synthesis, cellular
      signaling, cell cycle determination, apoptosis, metabolism, and stress responses
      through the negative regulation of signaling pathways initiated by protein
      kinases. Rapid progress is being made in the understanding of PP2A complex and
      its functions. Emerging studies have correlated changes in PP2A with human
      diseases, especially cancer. PP2A is comprised of 3 subunits: a catalytic
      subunit, a scaffolding subunit, and a regulatory subunit. The alternations of the
      subunits have been shown to be in association with many human malignancies.
      Therapeutic agents targeting PP2A inhibitors or activating PP2A directly have
      shed light on the therapy of cancers. This review focuses on PP2A structure,
      cancer-associated mutations, and the targeting of PP2A-related molecules to
      restore or reactivate PP2A in anticancer therapy, especially in digestive system
      cancer therapy. 

PMID- 24307894
TI  - Diagnosis and management of gastroesophageal reflux disease.

PMID- 24307895
TI  - Helicobacter pylori Infection in Dialysis Patients: A Meta-Analysis.
AB  - Background. Infection with Helicobacter pylori contributes to the
      etiopathogenesis of various extragastrointestinal conditions, yet its etiological
      association with either symptomatic or asymptomatic dialysis patients remains
      inconclusive. Methods. Two researchers working independently conducted a
      literature search of the online databases PubMed, EMBase, ScienceDirect, and
      Cochrane Central Register of Controlled Trials to identify relevant articles to
      the end of 2012. Case-control and cross-sectional studies that met the inclusion
      criteria were included. Results. Fifteen studies involving 1237 dialysis patients
      and 1568 controls with normal renal function were included. Compared with normal
      controls, dialysis patients overall were associated with a relatively lower risk
      of H. pylori infection though not statistically significant. A significant
      inverse association was found between H. pylori prevalence and duration of
      treatments in those who were dialyzed >4 years (odds ratio 0.28; 95% confidence
      interval 0.22-0.36, P < 0.00001). No relationship between H. pylori status and
      duration of dialysis was observed in CRF patients. There were no significant
      differences in endoscopic features between patients and controls. Conclusions.
      Our meta-analysis found no evidence of a significant association between
      infection with H. pylori and dialysis overall, whereas long-term treatments of
      more than four years had a significant protective effect. 

PMID- 24307896
TI  - Risk factors for urgency incontinence in women undergoing stress urinary
      incontinence surgery.
AB  - Objective. To determine baseline variables associated with urgency urinary
      incontinence (UUI) in women presenting for stress urinary incontinence (SUI)
      surgery. Methods. Baseline data from two randomized trials enrolling 1,252 women
      were analyzed: SISTEr (fascial sling versus Burch colposuspension) and TOMUS
      (retropubic versus transobturator midurethral sling). Demographic data, POP-Q
      measures, and validated measures of symptom severity and quality of life were
      collected. Charlson Comorbidity Index (CCI) and Patient Health Questionnaire-9
      were measured in TOMUS. Multivariate models were constructed with UUI and symptom
      severity as outcomes. Results. Over two-thirds of subjects reported bothersome
      UUI at baseline. TOMUS patients with more comorbidities had higher UDI irritative
      scores (CCI score 0 = 39.4, CCI score 1 = 42.1, and CCI score 2+ = 51.0, P =
      0.0003), and higher depression scores were associated with more severe UUI.
      Smoking, parity, prior incontinence surgery/treatment, prolapse stage, and
      incontinence episode frequency were not independently associated with UUI.
      Conclusions. There were no modifiable risk factors identified for patient
      reported UUI in women presenting for SUI surgery. However, the direct
      relationships between comorbidity level, depression, and worsening of UUI/urgency
      symptoms may represent targets for preoperative intervention. Further research is
      necessary to elucidate the pathophysiologic mechanisms that explain the
      associations between these medical conditions and bladder function. 

PMID- 24307897
TI  - Transport Reversal during Heteroexchange: A Kinetic Study.
AB  - It is known that secondary transporters, which utilize transmembrane ionic
      gradients to drive their substrates up a concentration gradient, can reverse the
      uptake and instead release their substrates. Unfortunately, the Michaelis-Menten
      kinetic scheme, which is popular in transporter studies, does not include
      transporter reversal, and it completely neglects the possibility of equilibrium
      between the substrate concentrations on both sides of the membrane. We have
      developed a complex two-substrate kinetic model that includes transport reversal.
      This model allows us to construct analytical formulas allowing the calculation of
      a "heteroexchange" and "transacceleration" using standard Michaelis coefficients
      for respective substrates. This approach can help to understand how glial and
      other cells accumulate substrates without synthesis and are able to release such
      substrates and gliotransmitters. 

PMID- 24307898
TI  - Mechanisms of perivascular adipose tissue dysfunction in obesity.
AB  - Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia,
      perivascular adipose tissue (PVAT) was considered only as a passive structural
      support for the vasculature, and it was routinely removed for isolated blood
      vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that
      PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important
      number of adipocyte-derived factors with physiological and pathophysiological
      paracrine vasoactive effects have been identified. PVAT undergoes structural and
      functional changes in obesity. During early diet-induced obesity, an adaptative
      overproduction of vasodilator factors occurs in PVAT, probably aimed at
      protecting vascular function. However, in established obesity, PVAT loses its
      anticontractile properties by an increase of contractile, oxidative, and
      inflammatory factors, leading to endothelial dysfunction and vascular disease.
      The aim of this review is to focus on PVAT dysfunction mechanisms in obesity. 

PMID- 24307900
TI  - Associations between Caries among Children and Household Sugar Procurement,
      Exposure to Fluoridated Water and Socioeconomic Indicators in the Brazilian
      Capital Cities.
AB  - The objective of this ecological study was to investigate the association between
      caries experience in 5- and 12-year-old Brazilian children in 2010 and household
      sugar procurement in 2003 and the effects of exposure to water fluoridation and
      socioeconomic indicators. Sample units were all 27 Brazilian capital cities. Data
      were obtained from the National Surveys of Oral Health; the National Household
      Food Budget Survey; and the United Nations Program for Development. Data analysis
      included correlation coefficients, exploratory factor analysis, and linear
      regression. There were significant negative associations between caries
      experience and procurement of confectionery, fluoridated water, HDI, and per
      capita income. Procurement of confectionery and soft drinks was positively
      associated with HDI and per capita income. Exploratory factor analysis grouped
      the independent variables by reducing highly correlated variables into two
      uncorrelated component variables that explained 86.1% of total variance. The
      first component included income, HDI, water fluoridation, and procurement of
      confectionery, while the second included free sugar and procurement of soft
      drinks. Multiple regression analysis showed that caries is associated with the
      first component. Caries experience was associated with better socioeconomic
      indicators of a city and exposure to fluoridated water, which may affect the
      impact of sugars on the disease. 

PMID- 24307899
TI  - Efficacy of goshajinkigan for oxaliplatin-induced peripheral neuropathy in
      colorectal cancer patients.
AB  - Objective. To evaluate the efficacy of Goshajinkigan for oxaliplatin-induced
      peripheral neuropathy in colorectal cancer patients. Patients. Colorectal cancer
      patients (N = 29) who received >=4 weeks of Goshajinkigan for oxaliplatin-induced
      peripheral neuropathy during chemotherapy at Kyoto Prefectural University of
      Medicine were (Goshajinkigan group) compared to 44 patients who had not received
      Goshajinkigan during the same period (non-Goshajinkigan group). Main Outcome
      Measures. The effect of Goshajinkigan was graded as curative, effective,
      stabilizing, or deleterious. The relationships between the grade of peripheral
      neuropathy and the dose of oxaliplatin in the Goshajinkigan and non-Goshajinkigan
      groups were evaluated. Results. The effect of Goshajinkigan on peripheral
      neuropathy in the Goshajinkigan group was curative, effective, stabilizing, and
      deleterious in 3.4, 20.7, 69.0, and 6.9% of patients, compared to the effect in
      the non-Goshajinkigan group (4.5, 15.9, 45.5, and 34.1%). The ratio of
      deleterious effects was significantly different between these two groups (P =
      0.04). A Kaplan-Meier analysis in relation to the cumulative dose of oxaliplatin
      showed that the incidence of grade 3 peripheral neuropathy tended to be less in
      the Goshajinkigan group (P = 0.05). There were no significant differences in time
      to treatment failure and severe adverse events between these two groups.
      Conclusions. Goshajinkigan prevented exacerbation of oxaliplatin-induced
      peripheral neuropathy. This trial is registered with UMIN000009956. 

PMID- 24307902
TI  - The assessment of disease activity in rheumatic diseases.

PMID- 24307901
TI  - Convergence of synapses, endosomes, and prions in the biology of
      neurodegenerative diseases.
AB  - Age-related misfolding and aggregation of disease-linked proteins in selective
      brain regions is a characteristic of neurodegenerative diseases. Although
      neuropathological aggregates that characterize these various diseases are found
      at sites other than synapses, increasing evidence supports the idea that synapses
      are where the pathogenesis begins. Understanding these diseases is hampered by
      our lack of knowledge of what the normal functions of these proteins are and how
      they are affected by aging. Evidence has supported the idea that
      neurodegenerative disease-linked proteins have a common propensity for prion
      protein-like cell-to-cell propagation. However, it is not thought that the prion
      like quality of these proteins/peptides that allows their cell-to-cell
      transmission implies a role for human-to-human spread in common age-related
      neurodegenerative diseases. It will be important to better understand the
      molecular and cellular mechanisms governing the role of these aggregating
      proteins in neural function, especially at synapses, how their propagation occurs
      and how pathogenesis is promoted by aging. 

PMID- 24307903
TI  - Long-Term Drug Survival of TNF Inhibitor Therapy in RA Patients: A Systematic
      Review of European National Drug Registers.
AB  - Objective. The present systematic review of RA registry data was undertaken to
      analyse the time on treatment of licensed TNF inhibitors in patients with RA in
      Europe. Methods. English language European registry studies comparing TNF
      inhibitors were searched using MEDLINE, Embase, Cochrane, and WHO: ICTRP up to 16
      April 2012 and proceedings of three selected conferences held between 2010 and
      2012. Pooled analysis was performed to determine drug survival rates for each TNF
      inhibitor. Results. Sixteen studies met the inclusion criteria, of which 11
      studies assessed biologic-naive patients and five studies included a mixed
      population of biologic-naive and biologic pretreated patients. The overall
      effectiveness of TNF inhibitors diminished with time, leading to decreased drug
      survival rates. Pooled drug survival rates after 60 months follow-up were 37%
      (infliximab), 48% (adalimumab), and 52% (etanercept). Further, in an
      observational study, when TNF inhibitors were used in combination with
      methotrexate, a longer drug survival was observed compared to TNF inhibitors
      alone. Conclusion. The findings of this systematic review indicated numerically
      lower drug discontinuation rates with etanercept than adalimumab, whereas
      infliximab had the highest rate. Further research is needed to understand the
      underlying mechanisms of treatment discontinuation with TNF inhibitors. 

PMID- 24307904
TI  - Unusual clinical presentation of ethylene glycol poisoning: unilateral facial
      nerve paralysis.
AB  - Ethylene glycol (EG) may be consumed accidentally or intentionally, usually in
      the form of antifreeze products or as an ethanol substitute. EG is metabolized to
      toxic metabolites. These metabolites cause metabolic acidosis with increased
      anion gap, renal failure, oxaluria, damage to the central nervous system and
      cranial nerves, and cardiovascular instability. Early initiation of treatment can
      reduce the mortality and morbidity but different clinical presentations can cause
      delayed diagnosis and poor prognosis. Herein, we report a case with the atypical
      presentation of facial paralysis, hematuria, and kidney failure due to EG
      poisoning which progressed to end stage renal failure and permanent right
      peripheral facial nerve palsy. 

PMID- 24307905
TI  - Concurrence of crossed cerebellar diaschisis and parakinesia brachialis oscitans
      in a patient with hemorrhagic stroke.
AB  - Crossed cerebellar diaschisis (CCD) is defined as a reduction in blood flow in
      the cerebellar hemisphere contralateral to the supratentorial focal lesion. The
      phenomenon termed parakinesia brachialis oscitans (PBO) in which stroke patients
      experience involuntary stretching of the hemiplegic arm during yawning is rarely
      reported. The concurrence of CCD and PBO has never been described. A 52-year-old
      man had putaminal hemorrhage and demonstrated no significant recovery in his left
      hemiplegia after intensive rehabilitation, but his gait improved gradually. Two
      months after the stroke, the single photon emission computed tomography (SPECT)
      showed CCD. Four months after the stroke, the patient noticed PBO. The follow-up
      SPECT showed persistent CCD and the patient's arm was still plegic. The frequency
      and intensity of PBO have increased with time since the stroke. We speculate that
      the two phenomena CCD and PBO might share similar neuroanatomical pathways and be
      valuable for predicting clinical recovery after stroke. 

PMID- 24307906
TI  - Papillary thyroid carcinoma with lung metastasis arising from dyshormonogenetic
      goiter: a case report.
AB  - Prior radiation exposure is the best known risk factor for thyroid cancers, and
      papillary thyroid carcinoma (PTC) may arise from dyshormonogenetic goiter. A 17
      year-old female patient was admitted to the department of chest diseases with
      respiratory symptoms. The patient had undergone a thyroid surgery for goiter at
      the age of 9. A bilateral nodular opacity was detected by radiological
      examination. The histopathologic examination of the specimen obtained from
      computed tomography guided trucut biopsy was diagnosed as PTC. We present a very
      rare case of PTC with lung metastasis that had undergone subtotal thyroidectomy
      due to dyshormonogenetic goiter eight years ago. 

PMID- 24307907
TI  - Radical cystectomy and lymphadenectomy to two patients with pelvic kidney:
      surgical pitfalls and considerations.
AB  - Our goal is to describe our experience in the difficulties encountered during
      radical cystectomy for muscle invasive bladder cancer in patients with
      contemporary pelvic kidney. Two patients with muscle invasive bladder cancer and
      contemporary pelvic kidney were subjected to radical cystectomy and extended
      lymphadenectomy with conversion to an ileal pouch. In both cases, lymphadenectomy
      was the first step after entering the true pelvis. In order to proceed to the
      cystoprostatectomy, careful dissection of the ectopic renal vessels and proper
      mobilization of the kidney were performed. In both cases, an ileal pouch was our
      choice. The pelvic kidney is the most common sight of renal ectopia. The etiology
      is the aborted ascent of the fetal kidney from its initial position in the
      pelvis. This is the first case series describing radical cystectomy for muscle
      invasive urothelial carcinoma of the bladder in patients with a pelvic kidney. 

PMID- 24307908
TI  - Do Not Be Fooled by Fancy Mutations: Inflammatory Fibroid Polyps Can Harbor
      Mutations Similar to Those Found in GIST.
AB  - Goal. Surgeons that remove a typical polyp from the stomach or small intestine
      should be reluctant to accept a diagnosis of GIST just because there is a
      mutation in platelet-derived growth factor receptor alfa (PDGFRA). Background. A
      subtype of gastric and intestinal polyps is denoted as inflammatory fibroid polyp
      (IFP). In some of these cases a mutation in PDGFRA is found, leading to the
      diagnosis of gastrointestinal stromal tumor (GIST). Study. This study includes
      two patients that had polyps removed from the ileum, and an extended
      investigation was performed with immunohistochemical staining and mutation
      analyses. Results. The tumors did not show typical immunohistochemical staining
      for markers used to diagnose GIST, but the mutation analysis revealed a mutation
      in PDGFRA exon 12. On the basis of the mutation analysis, both polyps were
      primarily diagnosed as GISTs, but the diagnosis was later changed to inflammatory
      fibroid polyp. Conclusion. It is important that both surgeons and pathologists be
      aware that IFP can harbor a mutation in PDGFRA where further treatment and follow
      up is different with the two different diagnoses. A mutation analysis can be
      misleading when taken out of the context of clinical observations, histological
      characteristics and immunohistochemical staining. 

PMID- 24307911
TI  - Wave-induced flow in meridians demonstrated using photoluminescent bioceramic
      material on acupuncture points.
AB  - The mechanisms of acupuncture remain poorly understood, but it is generally
      assumed that measuring the electrical conductivity at various meridians provides
      data representing various meridian energies. In the past, noninvasive methods
      have been used to stimulate the acupuncture points at meridians, such as heat,
      electricity, magnets, and lasers. Photoluminescent bioceramic (PLB) material has
      been proven to weaken hydrogen bonds and alter the characteristics of liquid
      water. In this study, we applied the noninvasive PLB technique to acupuncture
      point irradiation, attempting to detect its effects by using electrical
      conductivity measurements. We reviewed relevant literature, searching for
      information on meridians including their wave-induced flow characteristics. 

PMID- 24307912
TI  - Predicting the morphology of sickle red blood cells using coarse-grained models
      of intracellular aligned hemoglobin polymers.
AB  - Sickle red blood cells (SS-RBCs) exhibit heterogeneous cell morphologies (sickle,
      holly leaf, granular, etc.) in the deoxygenated state due to the polymerization
      of the sickle hemoglobin. Experimental evidence points to a close relationship
      between SS-RBC morphology and intracellular aligned hemoglobin polymers. Here, we
      develop a coarse-grained (CG) stochastic model to represent the growth of the
      intracellular aligned hemoglobin polymer domain. The CG model is calibrated based
      on the mechanical properties (Young's modulus, bending rigidity) of the sickle
      hemoglobin fibers reported in experiments. The process of the cell membrane
      transition is simulated for physiologic aligned hemoglobin polymer configurations
      and mean corpuscular hemoglobin concentration. Typical SS-RBC morphologies
      observed in experiments can be obtained from the current model as a result of the
      intracellular aligned hemoglobin polymer development without introducing any
      further ad hoc assumptions. It is found that the final shape of SS-RBCs is
      primarily determined by the angular width of the aligned hemoglobin polymer
      domain, but it also depends, to a lesser degree, on the polymer growth rate and
      the cell membrane rigidity. Cell morphologies are quantified by structural shape
      factors, which agree well with experimental results from medical images.

PMID- 24307910
TI  - Complementary and alternative medicine: a survey of its use in pediatric
      oncology.
AB  - Background. The use of complementary and alternative medicine (CAM) is high among
      children and youths with chronic illnesses, including cancer. The objective of
      this study was to assess prevalence and patterns of CAM use among pediatric
      oncology outpatients in two academic clinics in Canada. Procedure. A survey was
      developed to ask patients (or their parents/guardians) presenting to oncology
      clinics at the Stollery Children's Hospital in Edmonton and the Children's
      Hospital of Eastern Ontario (CHEO) in Ottawa about current or previous use of CAM
      products and practices. Results. Of the 137 families approached, 129 completed
      the survey. Overall CAM use was 60.5% and was not significantly different between
      the two hospitals. The most commonly reported reason for not using CAM was lack
      of knowledge about it. The most common CAM products ever used were multivitamins
      (86.5%), vitamin C (43.2%), cold remedies (28.4%), teething remedies (27.5%), and
      calcium (23.0%). The most common CAM practices ever used were faith healing
      (51.0%), massage (46.8%), chiropractic (27.7%), and relaxation (25.5%). Many
      patients (40.8%) used CAM products at the same time as prescription drugs.
      Conclusion. CAM use was high among patients at two academic pediatric oncology
      clinics. Although most respondents felt that their CAM use was helpful, many were
      not discussing it with their physicians. 

PMID- 24307909
TI  - Liver transplant tolerance and its application to the clinic: can we exploit the
      high dose effect?
AB  - The tolerogenic properties of the liver have long been recognised, especially in
      regard to transplantation. Spontaneous acceptance of liver grafts occurs in a
      number of experimental models and also in a proportion of clinical transplant
      recipients. Liver graft acceptance results from donor antigen-specific tolerance,
      demonstrated by the extension of tolerance to other grafts of donor origin. A
      number of factors have been proposed to be involved in liver transplant tolerance
      induction, including the release of soluble major histocompatibility (MHC)
      molecules from the liver, its complement of immunosuppressive donor leucocytes,
      and the ability of hepatocytes to directly interact with and destroy antigen
      specific T cells. The large tissue mass of the liver has also been suggested to
      act as a cytokine sink, with the potential to exhaust the immune response. In
      this review, we outline the growing body of evidence, from experimental models
      and clinical transplantation, which supports a role for large tissue mass and
      high antigen dose in the induction of tolerance. We also discuss a novel gene
      therapy approach to exploit this dose effect and induce antigen-specific
      tolerance robust enough to overcome a primed T cell memory response. 

PMID- 24307913
TI  - Statistical analysis of biomarkers for personalized medicine.

PMID- 24307914
TI  - Analytical solution of multicompartment solute kinetics for hemodialysis.
AB  - Objective. To provide an exact solution for variable-volume multicompartment
      kinetic models with linear volume change, and to apply this solution to a 4
      compartment diffusion-adjusted regional blood flow model for both urea and
      creatinine kinetics in hemodialysis. Methods. A matrix-based approach applicable
      to linear models encompassing any number of compartments is presented. The
      procedure requires the inversion of a square matrix and the computation of its
      eigenvalues lambda , assuming they are all distinct. This novel approach bypasses
      the evaluation of the definite integral to solve the inhomogeneous ordinary
      differential equation. Results. For urea two out of four eigenvalues describing
      the changes of concentrations in time are about 10(5) times larger than the other
      eigenvalues indicating that the 4-compartment model essentially reduces to the 2
      compartment regional blood flow model. In case of creatinine, however, the
      distribution of eigenvalues is more balanced (a factor of 10(2) between the
      largest and the smallest eigenvalue) indicating that all four compartments
      contribute to creatinine kinetics in hemodialysis. Interpretation. Apart from
      providing an exact analytic solution for practical applications such as the
      identification of relevant model and treatment parameters, the matrix-based
      approach reveals characteristic details on model symmetry and complexity for
      different solutes. 

PMID- 24307916
TI  - Survey Breakoffs in a Computer-Assisted Telephone Interview.
AB  - Nearly 23% of all telephone interviews in the most recently completed wave of the
      Panel Study of Income Dynamics break off at least once, requiring multiple
      sessions to complete the interview. Given this high rate, a study was undertaken
      to better understand the causes and consequences of temporary breakoffs in a
      computer-assisted telephone interview setting. The majority of studies examining
      breakoffs have been conducted in the context of self-administered web surveys.
      The present study uses new paradata collected on telephone interview breakoffs to
      describe their prevalence, associated field effort, the instrument sections and
      questions on which they occur, their source - whether respondent-initiated,
      interviewer-initiated, or related to telephone problems - and associations with
      respondent and interviewer characteristics. The results provide information about
      the survey response process and suggest a set of recommendations for instrument
      design and interviewer training, as well as additional paradata that should be
      collected to provide more insight into the breakoff phenomenon.

PMID- 24307915
TI  - Advances in multiphoton microscopy technology.
AB  - Multiphoton microscopy has enabled unprecedented dynamic exploration in living
      organisms. A significant challenge in biological research is the dynamic imaging
      of features deep within living organisms, which permits the real-time analysis of
      cellular structure and function. To make progress in our understanding of
      biological machinery, optical microscopes must be capable of rapid, targeted
      access deep within samples at high resolution. In this Review, we discuss the
      basic architecture of a multiphoton microscope capable of such analysis and
      summarize the state-of-the-art technologies for the quantitative imaging of
      biological phenomena.

PMID- 24307918
TI  - Racial Identity and Racial Treatment of Mexican Americans.
AB  - How racial barriers play in the experiences of Mexican Americans has been hotly
      debated. Some consider Mexican Americans similar to European Americans of a
      century ago that arrived in the United States with modest backgrounds but were
      eventually able to participate fully in society. In contrast, others argue that
      Mexican Americans have been racialized throughout U.S. history and this limits
      their participation in society. The evidence of persistent educational
      disadvantages across generations and frequent reports of discrimination and
      stereotyping support the racialization argument. In this paper, we explore the
      ways in which race plays a role in the lives of Mexican Americans by examining
      how education, racial characteristics, social interactions, relate to racial
      outcomes. We use the Mexican American Study Project, a unique data set based on a
      1965 survey of Mexican Americans in Los Angeles and San Antonio combined with
      surveys of the same respondents and their adult children in 2000, thereby
      creating a longitudinal and intergenerational data set. First, we found that
      darker Mexican Americans, therefore appearing more stereotypically Mexican,
      report more experiences of discrimination. Second, darker men report much more
      discrimination than lighter men and than women overall. Third, more educated
      Mexican Americans experience more stereotyping and discrimination than their less
      educated counterparts, which is partly due to their greater contact with Whites.
      Lastly, having greater contact with Whites leads to experiencing more
      stereotyping and discrimination. Our results are indicative of the ways in which
      Mexican Americans are racialized in the United States.

PMID- 24307917
TI  - Early lesions in lymphoid neoplasia: Conclusions based on the Workshop of the XV.
      Meeting of the European Association of Hematopathology and the Society of
      Hematopathology, in Uppsala, Sweden.
AB  - The increasing use of immunophenotypic and molecular techniques on lymphoid
      tissue samples without obvious involvement by malignant lymphoma has resulted in
      the increased detection of "early" lymphoid proliferations, which show some, but
      not all the criteria necessary for a diagnosis of malignant lymphoma. In most
      instances, these are incidental findings in asymptomatic individuals, and their
      biological behaviour is uncertain. In order to better characterize these
      premalignant conditions and to establish diagnostic criteria, a joint workshop of
      the European Association for Haematopathology and the Society of Hematopathology
      was held in Uppsala, Sweden, in September 2010. The panel reviewed and discussed
      more than 130 submitted cases and reached consensus diagnoses. Cases representing
      the nodal equivalent of monoclonal B-cell lymphocytosis (MBL) were discussed, as
      well as the "in situ" counterparts of follicular lymphoma (FL) and mantle cell
      lymphoma (MCL), topics that also stimulated discussions concerning the best
      terminology for these lesions. The workshop also addressed the borderland between
      reactive hyperplasia, and clonal proliferations such as pediatric marginal zone
      lymphoma and pediatric FL, which may have very limited capacity for progression.
      Virus-driven lymphoproliferations in the grey zone between reactive lesions and
      manifest malignant lymphoma were covered. Finally, early manifestations of T-cell
      lymphoma, both nodal and extranodal, and their mimics were addressed. This
      workshop report summarizes the most important conclusions concerning diagnostic
      features, as well as proposals for terminology and classification of early
      lymphoproliferations and tries to give some practical guidelines for diagnosis
      and reporting.

PMID- 24307919
TI  - Predicting (un)healthy behavior: A comparison of risk-taking propensity measures.
AB  - We compare four different risk-taking propensity measures on their ability to
      describe and to predict actual risky behavior in the domain of health. The risk
      taking propensity measures we compare are: (1) a general measure of risk-taking
      propensity derived from a one-item survey question (Dohmen et al., 2011), (2) a
      risk aversion index calculated from a set of incentivized monetary gambles (Holt
      & Laury, 2002), (3) a measure of risk taking derived from an incentive compatible
      behavioral task-the Balloon Analog Risk Task (Lejuez et al., 2002), and (4) a
      composite score of risk-taking likelihood in the health domain from the Domain
      Specific Risk Taking (DOSPERT) scale (Weber et al., 2002). Study participants are
      351 clients of health centers around Witbank, South Africa. Our findings suggest
      that the one-item general measure is the best predictor of risky health behavior
      in our population, predicting two out of four behaviors at the 5% level and the
      remaining two behaviors at the 10% level. The DOSPERT score in the health domain
      performs well, predicting one out of four behaviors at the 1% significance level
      and two out of four behaviors at the 10% level, but only if the DOSPERT
      instrument contains a hypothetical risk-taking item that is similar to the actual
      risky behavior being predicted. Incentivized monetary gambles and the behavioral
      task were unrelated to actual health behaviors; they were unable to predict any
      of the risky health behaviors at the 10% level. We provide evidence that this is
      not because the participants had trouble understanding the monetary trade-off
      questions or performed poorly in the behavioral task. We conclude by urging
      researchers to further test the usefulness of the one-item general measure, both
      in explaining health related risk-taking behavior and in other contexts.

PMID- 24307920
TI  - Local Wavelet-Based Filtering of Electromyographic Signals to Eliminate the
      Electrocardiographic-Induced Artifacts in Patients with Spinal Cord Injury.
AB  - Surface Electromyography (EMG) is a standard method used in clinical practice and
      research to assess motor function in order to help with the diagnosis of
      neuromuscular pathology in human and animal models. EMG recorded from trunk
      muscles involved in the activity of breathing can be used as a direct measure of
      respiratory motor function in patients with spinal cord injury (SCI) or other
      disorders associated with motor control deficits. However, EMG potentials
      recorded from these muscles are often contaminated with heart-induced
      electrocardiographic (ECG) signals. Elimination of these artifacts plays a
      critical role in the precise measure of the respiratory muscle electrical
      activity. This study was undertaken to find an optimal approach to eliminate the
      ECG artifacts from EMG recordings. Conventional global filtering can be used to
      decrease the ECG-induced artifact. However, this method can alter the EMG signal
      and changes physiologically relevant information. We hypothesize that, unlike
      global filtering, localized removal of ECG artifacts will not change the original
      EMG signals. We develop an approach to remove the ECG artifacts without altering
      the amplitude and frequency components of the EMG signal by using an externally
      recorded ECG signal as a mask to locate areas of the ECG spikes within EMG data.
      These segments containing ECG spikes were decomposed into 128 sub-wavelets by a
      custom-scaled Morlet Wavelet Transform. The ECG-related sub-wavelets at the ECG
      spike location were removed and a de-noised EMG signal was reconstructed.
      Validity of the proposed method was proven using mathematical simulated synthetic
      signals and EMG obtained from SCI patients. We compare the Root-mean Square Error
      and the Relative Change in Variance between this method, global, notch and
      adaptive filters. The results show that the localized wavelet-based filtering has
      the benefit of not introducing error in the native EMG signal and accurately
      removing ECG artifacts from EMG signals.

PMID- 24307921
TI  - Topical corticosteroid application and the structural and functional integrity of
      the epidermal barrier.
AB  - Topical corticosteroids are a very important part of the treatment of many skin
      disorders, especially eczematous dermatoses. When utilized properly and
      judiciously these agents often achieve excellent results in clearing or markedly
      improving many dermatological disorders. As some studies have shown, topical
      corticosteroids, despite their ability to decrease inflammation through several
      mechanisms, induce abnormalities in lipid synthesis and intercellular bilayer
      structure in the stratum corneum, which appear to prolong epidermal barrier
      recovery. These adverse effects may contribute to eariier eczematous flaring if
      measures to provide barrier repair are not undertaken. In addition, although
      topical corticosteroids are applied only to sites affected by the skin eruption,
      the incorporation of "barrier friendly" excipients into the vehicle that improve
      stratum corneum permeability barrier function and integrity is very rational. 

PMID- 24307922
TI  - Infrared camera evaluation of the cooling effect of triamcinolone acetonide
      aerosol.
AB  - OBJECTIVE: Triamcinolone acetonide spray is a topical corticosteroid indicated
      for the relief of inflammatory/pruritic manifestations of corticosteroid
      responsive dermatoses. There are clinical reports of an antipruritic, cooling
      sensation appreciated upon application. This study was designed to quantify the
      cryotherapeutic cooling effect of triamcinolone acetonide spray. DESIGN: Using an
      infrared video camera, skin surface temperature was evaluated for change upon
      application of the triamcinolone acetonide and two comparator ingredient
      components of triamcinolone acetonide: ethanol alcohol in a non-aerosolized spray
      and triamcinolone acetonide cream. SETTING: This was an open-label, single
      center, comparator study. PARTICIPANTS: This study enrolled 20 subjects with a
      diagnosis of either an acute or chronic steroid-responsive dermatosis. Ten
      additional controls were also enrolled. MEASUREMENTS: Using an infrared video
      camera, skin surface temperature was evaluated for change upon application of the
      triamcinolone acetonide and two comparator ingredient components of triamcinolone
      acetonide:ethanol alcohol in a non-aerosolized spray and triamcinolone acetonide
      cream. RESULTS: Across every study cohort, the average change in skin surface
      temperature with triamcinolone acetonide (between 16-18 degrees C; P<0.001 for
      all comparisons, Figures 1 and 2) was significantly greater than the change
      demonstrated by both the non-aerosolized spray (between 5-7 degrees C) and the
      triamcinolone acetonide cream (between 5.0-6.5 degrees C). CONCLUSION: The
      transient temperature change of nearly 20 degrees C with triamcinolone acetonide
      is most likely attributable to the refrigerant properties of the isobutane
      propellant of this product. Similar to other common cryotherapy methods,
      triamcinolone acetonide can achieve very low skin surface temperatures, which may
      result in localized relief of pruritus.

PMID- 24307923
TI  - Open-label treatment of moderate or marked melasma with a 4% hydroquinone skin
      care system plus 0.05% tretinoin cream.
AB  - OBJECTIVE: To evaluate treating epidermal melasma using a 4% hydroquinone skin
      care system plus tretinoin 0.05% cream. DESIGN: Multicenter open-label study with
      all patients receiving above-mentioned treatment for up to 24 weeks. SETTING:
      Private dermatology and plastic surgery clinics and clinical research facilities.
      PARTICIPANTS: Thirty-seven adult females with moderate or marked epidermal
      melasma, melasma pigmentation of mild-to-marked intensity and Fitzpatrick skin
      type III to VI. MEASUREMENTS: Melasma severity melasma pigmentation intensity
      melasma improvement, patient satisfaction, quality-of-life measures, erythema,
      dryness, peeling, burning/stinging. RESULTS: No patient discontinued due to lack
      of efficacy or treatment-related adverse events. Treatment was associated with a
      significant reduction from baseline in melasma severity and melasma pigmentation
      intensity from Week 4 onward (P<=0.001), and 100 percent of patients showed
      improvement from Week 8 onward. At Week 24, 100 percent of patients were
      "satisfied" or "very satisfied" with the overall effectiveness of their
      treatment. Patients' quality of life also improved (e.g., the proportion of
      patients feeling embarrassed or self-conscious about their skin "a lot" or "very
      much" declined from 78 percent at baseline to four percent at Week 24). Mean and
      median scores for erythema, dryness, peeling, and burning/stinging did not exceed
      trace levels. CONCLUSION: Treating moderate-to-severe melasma using the 4%
      hydroquinone skin care system plus 0.05% tretinoin can significantly reduce the
      severity of melasma and the intensity of melasma pigmentation within four weeks.
      Treatment was generally well tolerated and associated with an improved quality of
      life and high levels of patient satisfaction.

PMID- 24307924
TI  - Halometasone 0.05% cream in eczematous dermatoses.
AB  - OBJECTIVE: The authors aimed to document the real-life performance of
      halometasone 0.05% w/w cream in day-today practice through this multicenter, open
      label, Phase 4 study in India. METHODS: The authors enrolled 302 eligible
      patients either with acute or chronic eczema and treated them with halometasone
      0.05% cream daily. Efficacy variables (i.e., investigator's global assessment and
      pruritis severity score) were assessed at baseline and end of study. Physician's
      global evaluation of efficacy was assessed at the end of treatment. Treatment
      response was assessed as either a success or failure based on improvement in
      investigator's global assessment. RESULTS: Study population included 61.26
      percent male and 38.74 percent female participants, with the average age being
      30.79+/-14.52 (mean+/-SD) years. Contact dermatitis was seen in 22.52 percent of
      the study population. The mean (+/-SD) duration of primary diagnosis was 461.45
      days (+/-854.67). The most common type observed was "chronic" (60.49%), followed
      by "acute" (24.83%) conditions. Levocetirizine was the most commonly prescribed
      concomitant medication (31.39%), followed by emollients (15.33%). The mean and
      median duration of therapy was 18.50 and 25 days, respectively. Post therapy,
      there was a significant (p<0.0001) reduction in the severity of eczema and
      pruritus. Therapeutic success defined as cure (85.43%) and improvement (11.26%)
      was seen in 96.69 percent of patients. Physician's global evaluation of efficacy
      showed that in 96.67 percent of patients, treatment produced either an
      "excellent" (31.67%) or "good" (65.00%) response. Adverse events were reported in
      only 0.99 percent (3/302), with erythema being most common (0.66%). CONCLUSION:
      Halometasone is efficacious with a good safety and tolerability profile in
      patients with noninfected corticosteroid-responsive eczematous dermatoses.

PMID- 24307925
TI  - A review of trimethylaminuria: (fish odor syndrome).
AB  - Trimethylaminuria, better known as fish odor syndrome, is a psychologically
      disabling condition in which a patient emits a foul odor, which resembles that of
      rotting fish. The disorder is most commonly caused by an inherited deficiency in
      flavin monooxygenase 3, the vital enzyme for the metabolism of trimethylamine,
      which is the compound responsible for the unpleasant odor. The condition is
      uncommon, but there has been recent research to suggest that the diagnosis may
      often be overlooked. Moreover, it is important to be cognizant of this condition
      because there are reliable diagnostic tests and the disorder can be devastating
      from a psychosocial perspective. While there is no cure, many simple treatment
      options exist that may drastically improve the quality of life of these patients.
      This article will review the literature with an emphasis on the psychosocial
      impact and treatment options. 

PMID- 24307926
TI  - Atopic dermatitis and the stratum corneum: part 2: other structural and
      functional characteristics of the stratum corneum barrier in atopic skin.
AB  - This three-part review presents what is currently known about the involvement and
      interdependency of the epidermal barrier and immune response in the
      etiopathogenesis of atopic dermatitis. Part 1 of this review depicted the role of
      filaggrin in atopic dermatitis while this article, Part 2, evaluates the role of
      serine proteases and specific lipids in the structural and functional integrity
      of the stratum corneum and its multiple barrier functions in atopic dermatitis.
      Upregulation of serine protease activity causes adverse structural changes of the
      stratum corneum due to degradation of certain stratum corneum proteins that are
      integral to epidermal structure and functions, interference with the formation of
      the stratum corneum intercellular lipid membrane, which normally regulates
      epidermal water flux and gradient, and induction of a TH2 pattern of
      inflammation, which is the hallmark profile of atopic skin. Alteration in lipid
      ratios and changes in lipid-directed enzymes may play a role in the impairment of
      barrier functions that are associated with atopic dermatitis. In Part 3, immune
      dysregulation, including upregulation of a TH2 inflammation pattern, augmented
      allergic sensitization, sustained wound healing inflammation, and impaired innate
      immunity are discussed. The roles of the stratum corneum permeability barrier,
      the immune defense barrier, and antimicrobial barrier in AD pathogenesis are
      explained in detail. With this explanation, the interdependence of the multitude
      of polymorphisms and dysregulations seen in AD skin will become clear. The
      condensing of these impaired and/or dysregulated functions and how they interact
      should provide further knowledge about the pathogenic mechanisms that cause
      atopic dermatitis, how they are clinically relevant, and how they may assist in
      developing more specific therapies directed at the pathogenesis of atopic
      dermatitis. 

PMID- 24307927
TI  - Mitogenesis of vascular smooth muscle cell stimulated by platelet-derived growth
      factor-bb is inhibited by blocking of intracellular signaling by epigallocatechin
      3-O-gallate.
AB  - Epigallocatechin gallate (EGCG) is known to exhibit antioxidant,
      antiproliferative, and antithrombogenic effects and reduce the risk of
      cardiovascular diseases. Key events in the development of cardiovascular disease
      are hypertrophy and hyperplasia according to vascular smooth muscle cell
      proliferation. In this study, we investigated whether EGCG can interfere with
      PDGF-bb stimulated proliferation, cell cycle distribution, and the gelatinolytic
      activity of MMP and signal transduction pathways on RAOSMC when it was treated in
      two different ways-cotreatment with PDGF-bb and pretreatment of EGCG before
      addition of PDGF-bb. Both cotreated and pretreated EGCG significantly inhibited
      PDGF-bb induced proliferation, cell cycle progression of the G0/G1 phase, and the
      gelatinolytic activity of MMP-2/9 on RAOSMC. Also, EGCG blocked PDGF receptor
      beta (PDGFR-beta) phosphorylation on PDGF-bb stimulated RAOSMC under pretreatment
      with cells as well as cotreatment with PDGF-bb. The downstream signal
      transduction pathways of PDGFR-beta, including p42/44 MAPK, p38 MAPK, and Akt
      phosphorylation, were also inhibited by EGCG in a pattern similar to PDGFR-beta
      phosphorylation. These findings suggest that EGCG can inhibit PDGF-bb stimulated
      mitogenesis by indirectly and directly interrupting PDGF-bb signals and blocking
      the signaling pathway via PDGFR-beta phosphorylation. Furthermore, EGCG may be
      used for treatment and prevention of cardiovascular disease through blocking of
      PDGF-bb signaling. 

PMID- 24307928
TI  - PTSD in Depressed Mothers in Home Visitation.
AB  - Recent research has suggested that mothers participating in home visitation
      programs have a high incidence of mental health problems, particularly
      depression. Posttraumatic stress disorder (PTSD) is a common comorbidity with
      depression, yet its prevalence among home visiting populations and implications
      for parenting and maternal functioning have not been examined. This study
      contrasted depressed mothers with (n = 35) and without PTSD (n = 55) who were
      enrolled in a home visitation program. Results indicated that depressed mothers
      with comorbid PTSD were more likely to have experienced childhood sexual abuse,
      had greater severity of depressive symptoms, increased social isolation, and
      lower overall functioning than their counterparts without PTSD. Among PTSD
      mothers, greater severity of PTSD symptoms, in particular avoidance and emotional
      numbness, were associated with increased maternal psychopathology and parenting
      deficits even after controlling for depression severity. These findings add to
      the literature documenting the negative impacts of PTSD on maternal functioning
      and parenting. Implications for screening and treatment in the context of home
      visitation are discussed.

PMID- 24307929
TI  - The NLAAS Story: Some Reflections, Some Insights A commentary prepared for the
      special issue of the Asian American Journal of Psychology.

PMID- 24307930
TI  - The Generalized NEQ and Detectability Index for Tomosynthesis and Cone-Beam CT:
      From Cascaded Systems Analysis to Human Observers.
AB  - PURPOSE: In the early development of new imaging modalities - such as
      tomosynthesis and cone-beam CT (CBCT) - an accurate predictive model for imaging
      performance is particularly valuable in identifying the physical factors that
      govern image quality and guiding system optimization. In this work, a task-based
      cascaded systems model for detectability index is proposed that describes not
      only the signal and noise propagation in the 2D (projection) and 3D
      (reconstruction) imaging chain but also the influence of background anatomical
      noise. The extent to which generalized detectability index provides a valid
      metric for imaging performance was assessed through direct comparison to human
      observer experiments. METHODS: Detectability index (d') was generalized to
      include anatomical background noise in the same manner as the generalized noise
      equivalent quanta (NEQ) proposed by Barrett et al. (Proc. SPIE Med. Imaging, Vol.
      1090, 1989). Anatomical background noise was measured from a custom phantom
      designed to present power-law spectral density comparable to various anatomical
      sites (e.g., breast and lung). Theoretical calculations of d' as a function of
      the source-detector orbital extent (thetatot) was obtained from a 3D cascaded
      systems analysis model for tomosynthesis and cone-beam CT (CBCT). Four model
      observers were considered in the calculation of d': prewhitening (PW), non
      prewhitening (NPW), prewhitening with eye filter and internal noise (PWE), and
      non-prewhitening with eye filter and internal noise (NPWE). Human observer
      performance was measured from 9AFC tests for a variety of idealized imaging tasks
      presented within a clutter phantom. Theoretical results (d') were converted to
      area under the ROC curve (Az ) and compared directly to human observer
      performance as a function of imaging task and orbital extent. RESULTS:
      Theoretical results demonstrated reasonable correspondence with human observer
      response for all tasks across the continuum in thetatot ranging from low-angle
      tomosynthesis (thetatot ~10 degrees ) to CBCT (thetatot ~180 degrees ). Both
      theoretical and experimental Az were found to increase with acquisition angle,
      consistent with increased rejection of out-of-plane clutter for larger
      tomosynthesis angle. Of the four theoretical model observers considered, the
      prewhitening models tended to overestimate real observer performance, while the
      non-prewhitening models demonstrated reasonable agreement. CONCLUSIONS:
      Generalized detectability index was shown to provide a meaningful metric for
      imaging performance, helping to bridge the gap between real observer performance
      and prevalent Fourier-based metrics based in first principles of spatial
      frequency-dependent NEQ and imaging task.

PMID- 24307931
TI  - Drought-induced trans-generational tradeoff between stress tolerance and defence:
      consequences for range limits?
AB  - Areas just across species range boundaries are often stressful, but even with
      ample genetic variation within and among range-margin populations, adaptation
      towards stress tolerance across range boundaries often does not occur. Adaptive
      trans-generational plasticity should allow organisms to circumvent these problems
      for temporary range expansion; however, range boundaries often persist. To
      investigate this dilemma, we drought stressed a parent generation of Boechera
      stricta (A.Gray) A. Love & D. Love, a perennial wild relative of Arabidopsis,
      representing genetic variation within and among several low-elevation range
      margin populations. Boechera stricta is restricted to higher, moister elevations
      in temperate regions where generalist herbivores are often less common. Previous
      reports indicate a negative genetic correlation (genetic tradeoff) between
      chemical defence allocation and abiotic stress tolerance that may prevent the
      simultaneous evolution of defence and drought tolerance that would be needed for
      range expansion. In growth chamber experiments, the genetic tradeoff became
      undetectable among offspring sib-families whose parents had been drought treated,
      suggesting that the stress-induced trans-generational plasticity may circumvent
      the genetic tradeoff and thus enable range expansion. However, the trans
      generational effects also included a conflict between plastic responses
      (environmental tradeoff); offspring whose parents were drought treated were more
      drought tolerant, but had lower levels of glucosinolate toxins that function in
      defence against generalist herbivores. We suggest that either the genetic or
      environmental tradeoff between defence allocation and stress tolerance has the
      potential to contribute to range limit development in upland mustards. 

PMID- 24307933
TI  - Calcium-sensing receptor regulates blood calcium independent of PTH.

PMID- 24307934
TI  - BP use is associated with an increased risk of atypical femoral fractures.

PMID- 24307932
TI  - Structural location determines functional roles of the basic amino acids of KR
      12, the smallest antimicrobial peptide from human cathelicidin LL-37.
AB  - Cationic antimicrobial peptides are recognized templates for developing a new
      generation of antimicrobials to combat superbugs. Human cathelicidin LL-37 is an
      essential host defense molecule in human innate immunity. Previously, we
      identified KR-12 as the smallest antibacterial peptide of LL-37. KR-12 has a
      narrow activity spectrum since it is active against Gram-negative Escherichia
      coli but not Gram-positive Staphylococcus aureus. The functional roles of the
      basic amino acids of KR-12, however, have not yet been elucidated. An alanine
      scan of cationic amino acids of KR-12 provided evidence for their distinct roles
      in the activities of the peptides. Bacterial killing and membrane permeation
      experiments indicate that the R23A and K25A mutants, as well as the lysine-to
      arginine mutant, were more potent than KR-12. Another three cationic residues
      (K18, R19, and R29) of KR-12, which are located in the hydrophilic face of the
      amphiphathic helix, appeared to be more important in clustering anionic lipids or
      hemolysis than R23 and K25 in the interfacial region. While the loss of
      interfacial R23 or K25 reduced peptide helicity, underscoring its important role
      in membrane binding, the overall increase in peptide activity of KR-12 could be
      ascribed to the increased peptide hydrophobicity that outweighed the role of
      basic charge in this case. In contrast, the mutations of interfacial R23 or K25
      reduced peptide bactericidal activity of GF-17, an overlapping, more hydrophobic
      and potent peptide also derived from LL-37. Thus, the hydrophobic context of the
      peptide determines whether an alanine substitution of an interfacial basic
      residue increases or decreases membrane permeation and peptide activity.

PMID- 24307935
TI  - ITGA1 gene locus may shed light on osteoporosis-type 2 diabetes link.

PMID- 24307936
TI  - AZT 5'-Phosphonates: Achievements and Trends in the Treatment and Prevention of
      HIV Infection.
AB  - Despite the numerous drawbacks, 3'-azido-3'-deoxythymidine (AZT, Zidovudine,
      Retrovir) remains one of the key drugs used in the treatment and prevention of
      HIV infection in both monotherapy and HAART. A strategy in searching for new
      effective and safe AZT agents among latent (depot) forms of AZT has yielded its
      first positive results. In particular, the sodium salt of AZT 5'-H-phosphonate
      (Nikavir, phosphazide) has demonstrated clinical advantages over parent AZT:
      first and foremost, lower toxicity and better tolerability. It can be effectively
      used for the prevention of vertical transmission from mothers to babies and as an
      alternative drug for HIV-infected patients with low tolerance to Zidovudine.
      Preclinical studies of another phosphonate, AZT 5'-aminocarbonylphosphonate, have
      demonstrated that it releases AZT when taken orally. Pharmacokinetic studies have
      shown a prolonged action potential. Based on the analysis of both toxicological
      and pharmacological data, AZT 5'-aminocarbonylphosphonate has been recommended
      for clinical trials. 

PMID- 24307938
TI  - Transfer of Silver Nanoparticles through the Placenta and Breast Milk during in
      vivo Experiments on Rats.
AB  - Silver nanoparticles (NPs), widely used in the manufacture of various types of
      consumer products and for medical applications, belong to novel types of
      materials that pose potential risks to human health. The potential negative
      effects of the influence of these NPs on reproduction are insufficiently
      researched. A quantitative assessment of the transfer of metallic silver
      nanoparticles through the placenta and breast milk was carried out during an in
      vivo experiment. We used 34.9 +/- 14.8 nm in size silver NPs that were stabilized
      by low-molecularweight polyvinylpyrrolidone and labeled with the (110m)Ag
      radioactive isotope using thermal neutron irradiation in a nuclear reactor.
      [(110m)Ag]-labeled NPs preparations were administered intragastrically via a
      gavage needle to pregnant (20(th) day of gestation) or lactating (14-16th day of
      lactation) female rats at a dose of 1.69-2.21 mg/kg of body weight upon
      conversion into silver. The accumulation of NPs in rat fetuses and infant rats
      consuming their mother's breast milk was evaluated using a low-background
      semiconductor gamma-ray spectrometer 24 and 48 hours following labeling,
      respectively. In all cases, we observed a penetration of the [(110m)Ag]-labeled
      NPs through the placenta and ther entry into the mother's milk in amounts
      exceeding by 100-1,000 times the sensitivity of the utilized analytical method.
      The average level of accumulation of NPs in fetuses was 0.085-0.147% of the
      administered dose, which was comparable to the accumulation of the label in the
      liver, blood, and muscle carcass of adult animals and exceeded the penetration of
      NPs across the hematoencephalic barrier into the brain of females by a factor of
      10-100. In lactating females, the total accumulation of [(110m)Ag]-labeled NPs
      into the milk exceeded 1.94 +/- 0.29% of the administered dose over a 48 h period
      of lactation; not less than 25% of this amount was absorbed into the
      gastrointestinal tract of infant rats. Thus, this was the first time experimental
      evidence of the transfer of NPs from mother to offspring through the placenta and
      breast milk was obtained. 

PMID- 24307937
TI  - Clathrin-mediated endocytosis and adaptor proteins.
AB  - Macromolecules gain access to the cytoplasm of eukaryotic cells using one of
      several ways of which clathrin-dependent endocytosis is the most researched.
      Although the mechanism of clathrin-mediated endocytosis is well understood in
      general, novel adaptor proteins that play various roles in ensuring specific
      regulation of the mentioned process are being discovered all the time. This
      review provides a detailed account of the mechanism of clathrin-mediated
      internalization of activated G protein-coupled receptors, as well as a
      description of the major proteins involved in this process. 

PMID- 24307939
TI  - Should we consider patients with coexistent hepatitis B or C infection for
      orthotopic heart transplantation?
AB  - Heart transplantation (HTX) is the gold standard surgical treatment for patients
      with advanced heart failure. The prevalence of hepatitis B and hepatitis C
      infection in HTX recipients is over 10%. Despite its increased prevalence, the
      long-term outcome in this cohort is still not clear. There is a reluctance to
      place these patients on transplant waiting list given the increased incidence of
      viral reactivation and chronic liver disease after transplant. The emergence of
      new antiviral therapies to treat this cohort seems promising but their long-term
      outcome is yet to be established. The aim of this paper is to review the
      literature and explore whether it is justifiable to list advanced heart failure
      patients with coexistent hepatitis B/C infection for HTX. 

PMID- 24307941
TI  - In silico insights of L-glutamate: structural features in vacuum and in complex
      with its receptor.
AB  - Structural properties of the glutamate in vacuum and in complex with its receptor
      were analyzed. The analysis was focused on global properties, attempting to
      characterize features such as overall flexibility and common trends in the
      conformation set. The glutamate, as other ligands in complex with the receptor,
      adopts a spatial conformation that corresponds to one of the possible molecular
      equilibrium states in physiological conditions. The glutamate forms an extended
      structure for all cases, but the energy of the glutamate round out form is lower
      than the extended glutamate form. The results showed the glutamate as a flexible
      molecule, which can easily adapt to different interacting environments, and it
      can be considered as an approximation to address why glutamate interacts with a
      great number of molecules. 

PMID- 24307942
TI  - Pivotal role of mediterranean dietary regimen in the increase of serum magnesium
      concentration in patients with coronary artery disease.
AB  - Background. Recent studies confirmed cardioprotective role of intravenous
      magnesium for the prevention of cardiac events, but effect of dietary intake of
      this mineral via recommended dietary regimens on control and inhibition of
      coronary artery disease (CAD) risk factors has been questioned. The aim of the
      present study was to determine effect of Mediterranean dietary approach on serum
      magnesium concentration among Iranian patients with CAD. Method. Baseline
      characteristics and clinical data of 102 consecutive patients with the diagnosis
      of CAD and candidates for isolated coronary artery bypass surgery were entered
      into the study. Laboratory parameters especially serum magnesium concentration
      were measured after 12-14 h of overnight fasting and before operation.
      Nutritional status was assessed by food frequency questionnaire and the diet
      score was calculated on the basis of Mediterranean diet quality index (Med-DQI).
      Results. No significant differences were found in the concentrations of albumin,
      last fasting blood sugar, last creatinine, and lipid profiles between the groups
      with Mediterranean dietary score < 5 and the group with higher dietary score;
      however, serum magnesium concentration in the first group was higher than that in
      the group with higher dietary score. Linear multivariate regression analysis
      showed that the lower Mediterranean dietary score was a predictor for serum
      magnesium concentration after adjusting for confounders. Conclusion. Taking
      Mediterranean dietary regimen can be associated with increased level of serum
      magnesium concentration, and thus this regimen can be cardioprotective because of
      its effects on serum magnesium. 

PMID- 24307943
TI  - The exposure assessment in current time study: implementation, feasibility, and
      acceptability of real-time data collection in a community cohort of illicit drug
      users.
AB  - Objective. We describe the study design and evaluate the implementation,
      feasibility, and acceptability of an ecological momentary assessment (EMA) study
      of illicit drug users. Design. Four sequential field trials targeting observation
      of 30 individuals followed for a four week period. Participants. Participants
      were recruited from an ongoing community-cohort of current or former injection
      drug users. Of 113 individuals enrolled, 109 completed study procedures during
      four trials conducted from November 2008 to May 2013. Methods. Hand-held
      electronic diaries used in the initial trials were transitioned to a smartphone
      platform for the final trial with identical data collection. Random-prompts
      delivered five times daily assessed participant location, activity, mood, and
      social context. Event-contingent data collection involved participant self
      reports of illicit drug use and craving. Main Outcome Measures. Feasibility
      measures included participant retention, days of followup, random-prompt response
      rates, and device loss rate. Acceptability was evaluated from an end-of-trial
      questionnaire. Sociodemographic, behavioral, clinical, and trial characteristics
      were evaluated as correlates of weekly random-prompt response rates >=80% using
      logistic regression with generalized estimating equations. Results. Study
      participants were a median of 48.5 years old, 90% African American, 52% male, and
      59% HIV-infected with limited income and educational attainment. During a median
      followup of 28 days, 78% of 11,181 random-prompts delivered were answered (mean
      of 2.8 responses daily), while 2,798 participant-initiated events were reported
      (30% drug use events; 70% craving events). Self-reported acceptability to study
      procedures was uniformly favorable. Device loss was rare (only 1 lost device
      every 190 person-days of observation). Higher educational attainment was
      consistently associated with a higher response rate to random-prompts, while an
      association of HIV infection with lower response rates was not observed after
      accounting for differences in trial recruitment procedures. Conclusion. Near real
      time EMA data collection in the field is feasible and acceptable among community
      dwelling illicit drug users. These data provide the basis for future studies of
      EMA-informed interventions to prevent drug relapse and improve HIV treatment
      outcomes in this population. 

PMID- 24307944
TI  - Adnexal Masses Treated Using a Combination of the SILS Port and Noncurved
      Straight Laparoscopic Instruments: Turkish Experience and Review of the
      Literature.
AB  - Objective. To report our experience treating adnexal masses using a combination
      of the SILS port and straight nonroticulating laparoscopic instruments. Study
      Design. This prospective feasibility study included 14 women with symptomatic and
      persistent adnexal masses. Removal of adnexal masses via single-incision
      laparoscopic surgery using a combination of the SILS port and straight
      nonroticulating laparoscopic instruments was performed. Results. All of the
      patients had symptomatic complex adnexal masses. Mean age of the patients was
      38.4 years (range: 21-61 years) and mean duration of surgery was 71 min (range:
      45-130 min). All surgeries were performed using nonroticulating straight
      laparoscopic instruments. Mean tumor diameter was 6 cm (range: 5-12 cm). All
      patient pathology reports were benign. None of the patients converted to
      laparotomy. All the patients were discharged on postoperative d1.
      Postoperatively, all the patients were satisfied with their incision and cosmetic
      results. Conclusion. All 14 patients were successfully treated using standard,
      straight nonroticulating laparoscopic instruments via the SILS port. This
      procedure can reduce the cost of treatment, which may eventually lead to more
      widespread use of the SILS port approach. Furthermore, concomitant surgical
      procedures are possible using this approach. However, properly designed
      comparative studies with single port and classic laparoscopic surgery are
      urgently needed. 

PMID- 24307940
TI  - Dendritic cell-based approaches for therapeutic immune regulation in solid-organ
      transplantation.
AB  - To avoid immune rejection, allograft recipients require drug-based
      immunosuppression, which has significant toxicity. An emerging approach is
      adoptive transfer of immunoregulatory cells. While mature dendritic cells (DCs)
      present donor antigen to the immune system, triggering rejection, regulatory DCs
      interact with regulatory T cells to promote immune tolerance. Intravenous
      injection of immature DCs of either donor or host origin at the time of
      transplantation have prolonged allograft survival in solid-organ transplant
      models. DCs can be treated with pharmacological agents before injection, which
      may attenuate their maturation in vivo. Recent data suggest that injected
      immunosuppressive DCs may inhibit allograft rejection, not by themselves, but
      through conventional DCs of the host. Genetically engineered DCs have also been
      tested. Two clinical trials in type-1 diabetes and rheumatoid arthritis have been
      carried out, and other trials, including one trial in kidney transplantation, are
      in progress or are imminent. 

PMID- 24307945
TI  - Intravenous paracetamol reduces postoperative opioid consumption after orthopedic
      surgery: a systematic review of clinical trials.
AB  - Postoperative pain management is one of the most challenging jobs in orthopedic
      surgical population as it comprises of patients from extremes of ages and with
      multiple comorbidities. Though effective, opioids may contribute to serious
      adverse effects particularly in old age patients. Intravenous paracetamol is
      widely used in the postoperative period with the hope that it may reduce opioid
      consumption and produce better pain relief. A brief review of human clinical
      trials where intravenous paracetamol was compared with placebo or no treatment in
      postoperative period in orthopedic surgical population has been done here. We
      found that four clinical trials reported that there is a significant reduction in
      postoperative opioid consumption. When patients received an IV injection of 2 g
      propacetamol, reduction of morphine consumption up to 46% has been reported.
      However, one study did not find any reduction of opioid requirement after spinal
      surgery in children and adolescent. Four clinical trials reported better pain
      scores when paracetamol has been used, but other three trials denied. We conclude
      that postoperative intravenous paracetamol is a safe and effective adjunct to
      opioid after orthopedic surgery, but at present there is no data to decide
      whether paracetamol reduces opioid related adverse effects or not. 

PMID- 24307946
TI  - Urinary Tract Infections due to Multidrug-Resistant Enterobacteriaceae:
      Prevalence and Risk Factors in a Chicago Emergency Department.
AB  - Background. Selection of empiric antibiotics for urinary tract infections (UTIs)
      has become more challenging because of the increasing rates of multidrug
      resistant Enterobacteriaceae (MDRE) infections. Methods. This retrospective study
      was conducted to determine antibiotic resistance patterns, risk factors, and
      appropriate empiric antibiotic selection for MDRE UTIs. Adult patients seen in
      the Emergency Department (ED) with Enterobacteriaceae UTIs during 2008-2009 were
      identified from review of microbiology records. MDRE were defined as organisms
      resistant to at least 3 categories of antibiotics. Results. There were 431
      eligible patients; 83 (19%) had MDRE UTIs. Resistance rates for individual
      antibiotics among MDRE UTIs were significantly greater than non-MDRE UTIs:
      levofloxacin, 72% versus 14%; TMP-SMX, 77% versus 12%; amoxicillin-clavulanate,
      35% versus 4%; nitrofurantoin, 21% versus 12%, and ceftriaxone, 20% versus 0%.
      All Enterobacteriaceae isolates were susceptible to ertapenem (MIC <= 2 mg/L).
      Independent risk factors for MDRE UTI were prior fluoroquinolone use within 3
      months (adjusted odds ratio (aOR) 3.64; P = 0.001), healthcare-associated risks
      (aOR 2.32; P = 0.009), and obstructive uropathy (aOR 2.22; P = 0.04). Conclusion.
      Our study suggests that once-daily intravenous or intramuscular ertapenem may be
      appropriate for outpatient treatment of ED patients with MDRE UTI. 

PMID- 24307947
TI  - Grape seed proanthocyanidin rescues rats from steatosis: a comparative and
      combination study with metformin.
AB  - Nonalcoholic fatty liver disease (NAFLD), a premorbid condition, lacks proper
      management owing to multitude of abnormalities. In this study, we compared the
      effects of a potent antioxidant, grape seed proanthocyanidins (GSP), and an
      insulin sensitizer, metformin (MET), in high-fat-fructose-diet- (HFFD-) induced
      albino Wistar rat model of NAFLD. Either GSP (100 mg/Kg b.w) or MET (50 mg/Kg
      b.w) or both were administered as therapeutic options. HFFD-fed rats showed
      abnormal plasma lipid profile, inflammation, and steatosis of the liver when
      examined by biochemical and histology techniques. Increased lipid storage,
      lipogenesis, and reduced lipolysis were evident from mRNA expression studies of
      hepatic lipid droplets (LD) proteins, sterol regulatory element binding 1c (SREBP
      1c), and peroxisome proliferator activated receptor- alpha (PPAR- alpha ). GSP
      administration to HFFD-fed rats caused 69% reduction in hepatic TG levels,
      whereas MET caused only 23%. The combination treatment reduced TG levels by 63%.
      GSP reduced the mRNA expression of SREBP1c and LD proteins and increased that of
      PPAR- alpha more effectively compared to MET in HFFD-induced hyperlipidemic rats.
      Combination of MET and GSP improved the metabolism of lipids effectively, but the
      effect was not additive in restoring lipid levels. 

PMID- 24307948
TI  - Effect of Commercial Cyanobacteria Products on the Growth and Antagonistic
      Ability of Some Bioagents under Laboratory Conditions.
AB  - Evaluation of the efficacy of blue-green algal compounds against the growth of
      either pathogenic or antagonistic microorganisms as well as their effect on the
      antagonistic ability of bioagents was studied under in vitro conditions. The
      present study was undertaken to explore the inhibitory effect of commercial algal
      compounds, Weed-Max and Oligo-Mix, against some soil-borne pathogens. In growth
      medium supplemented with these algal compounds, the linear growth of pathogenic
      fungi decreased by increasing tested concentrations of the two algal compounds.
      Complete reduction in pathogenic fungal growth was observed at 2% of both Weed
      Max and Oligo-Mix. Gradual significant reduction in the pathogenic fungal growth
      was caused by the two bioagents and by increasing the concentrations of algal
      compounds Weed-Max and Oligo-Mix. The present work showed that commercial algal
      compounds, Weed-Max and Oligo-Mix, have potential for the suppression of soil
      borne fungi and enhance the antagonistic ability of fungal, bacterial, and yeast
      bio-agents. 

PMID- 24307949
TI  - Asthma Control and Its Relationship with Obstructive Sleep Apnea (OSA) in Older
      Adults.
AB  - Background/Objectives. Asthma in older individuals is poorly understood. We aimed
      to characterize the older asthma phenotype and test its association with
      obstructive sleep apnea (OSA). Design. Cross-sectional. Setting. Pulmonary and
      Asthma/Allergy clinics. Participants. 659 asthma subjects aged 18-59 years
      (younger) and 154 aged 60-75 (older). Measurements. Sleep Apnea scale of Sleep
      Disorders Questionnaire (SA-SDQ), asthma severity step (1-4, severe if step 3 or
      4), established OSA diagnosis, continuous positive airway pressure (CPAP) use,
      and comorbidities. Results. Older versus younger had worse control, as assessed
      by asthma step, lung function, and inhaled corticosteroid use. Among older
      subjects, after controlling for known asthma aggravators, OSA diagnosis was the
      only factor robustly associated with severe asthma: on average, OSA was
      associated with nearly 7 times greater likelihood of severe asthma in an older
      individual (OR = 6.67). This relationship was of greater magnitude than in
      younger subjects (OR = 2.16). CPAP use attenuated the likelihood of severe asthma
      in older subjects by 91% (P = 0.005), much more than in the younger asthmatics.
      Conclusion. Diagnosed OSA increases the risk for worse asthma control in older
      patients, while CPAP therapy may have greater impact on asthma outcomes.
      Unrecognized OSA may be a reason for poor asthma control, particularly among
      older patients. 

PMID- 24307950
TI  - Practical medical management of Crohn's disease.
AB  - Crohn's disease is a chronic inflammatory disease of diagnostic and therapeutic
      challenges. After proper diagnosis, treatment decisions must be made on precise
      clinical judgment. During the course of the disease there are variable clinical
      features, so each case must be managed individually. Physicians who care for
      patients with Crohn's disease should be prepared for treatment options in
      different states of the disease and possible complications of both the disease
      and medications. This paper will focus on the management of Crohn's disease. We
      aim to discuss current treatment options in different presentations of the
      disease and to provide algorithmic management strategy. 

PMID- 24307951
TI  - Aspirin use in rheumatoid arthritis patients with increased risk of
      cardiovascular disease.
AB  - Objectives. To examine the patterns of low-dose aspirin use in rheumatoid
      arthritis (RA) patients with high risk for coronary artery disease (CAD).
      Methods. Cross-sectional study of 36 consecutive RA patients with a Framingham
      score >=10% for CAD. Eligible RA patients were provided with a questionnaire on
      CAD risk factors and use of low-dose aspirin. For aspirin nonusers, the reason
      for nonuse was requested by both the patient and rheumatologist. Questions for
      patients included physician's advice, self-preference, history of
      gastrointestinal bleeding, allergy to aspirin, or concomitant use of other anti
      inflammatory medications. Questions for rheumatologists included awareness of the
      increased CAD risk, attribution, patient preference, history of gastrointestinal
      bleeding, allergy to aspirin, and medication interactions. Results. Patients
      participated in the study; 8 patients reported using daily aspirin, while 23
      patients did not. The main reason cited by patients for not taking aspirin was
      that they were not instructed by their primary care physician (PCP) to do so (n =
      16), which was also the main reason cited by rheumatologists (n = 9). Conclusion.
      This study confirmed underutilization of aspirin in RA patients at high risk for
      CAD, largely due to the perception that this is an issue which should be handled
      by the PCP. 

PMID- 24307952
TI  - Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin-Receptor
      Blockers (ARBs) in Patients at High Risk of Cardiovascular Events: A Meta
      Analysis of 10 Randomised Placebo-Controlled Trials.
AB  - Context. Whether angiotensin converting-enzyme inhibitors (ACEI) and angiotensin
      receptor blockers (ARB) are useful in high risk patients without heart failure is
      unclear. We perform a meta-analysis of prospective randomized placebo-controlled
      ACEI or ARB trials studying patients with a combination of risk factors to assess
      treatment impact on all cause mortality, cardiovascular mortality, nonfatal
      myocardial infarction (MI) and stroke. Method. A PubMed search was made for
      placebo-controlled trials recruiting at least 1,200 high risk patients randomized
      to either ACEI or ARB, with follow-up of at least 2 years. Meta-analysis was
      performed using the RevMan 5 program and Mantel-Haenszel analysis was done with a
      fixed effects model. Results. Ten trials recruiting 77,633 patients were
      reviewed. All cause mortality was significantly reduced by ACEI (RR 0.89; P =
      0.0008), but not by ARB treatment (RR 1.00; P = 0.89). Cardiovascular mortality
      and nonfatal MI were also reduced in the ACEI trials but not with ARB therapy.
      Stroke was significantly reduced in the ACEI trials (RR 0.75; P < 0.00001) and
      more modestly reduced in the ARB trials (RR 0.90; P = 0.01). Conclusion. ACEI
      treatment reduced stroke, nonfatal MI, cardiovascular and total mortality in high
      risk patients, while ARB modestly reduced stroke with no effect on nonfatal MI,
      cardiovascular and total mortality. 

PMID- 24307953
TI  - Protective Effects of Resveratrol against Chronic Immobilization Stress on
      Testis.
AB  - Objective. The aim of this study was to investigate protective effects of
      resveratrol, a strong antioxidant, against possible negative effects of chronic
      immobilization stress on testes of male rats histochemically,
      immunohistochemically, ultrastructurally, and biochemically. Material and
      Methods. Male Wistar rats were divided into 4 groups (n = 7). Group I, control
      group (C), was not exposed to stress. Group II, stress group (S), was exposed to
      chronic immobilization stress. In Group III, low dose resveratrol + stress group
      (LRS), rats were given 10 mg/kg/day resveratrol just before the stress
      application. In Group IV, high dose resveratrol + stress group (HRS), rats were
      given 20 mg/kg/day resveratrol just before the stress application. For chronic
      immobilization stress application animals were put in the plastic tubes (6 cm in
      diameter, 15 cm in length) during 32 days for 6 hours. All animals were
      sacrificed 18 hours after the last stress application. Results. Histochemical and
      ultrastructural investigations showed that in stress group there was germ cell
      deprivation in seminiferous tubules and increase of connective tissue on
      interstitial area. No significant changes were seen in low and high dose
      resveratrol groups. After immunohistochemical investigations, TUNEL (+) and
      Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group
      compared with those control group, but they were decreased in low and high dose
      resveratrol groups. According to biochemically results, MDA, GSH, and
      testosterone levels in stress group showed no significant difference when
      compared with those of the other groups. Conclusion. The chronic immobilization
      stress increases oxidative stress and apoptosis and causes histological tissue
      damages; resveratrol can minimize the histological damage in testes
      significantly. 

PMID- 24307954
TI  - Nasopalatine duct cyst.
AB  - The nasopalatine cyst is the most common epithelial and nonodontogenic cyst of
      the maxilla. The cyst originates from epithelial remnants from the nasopalatine
      duct. The cells may be activated spontaneously during life or are eventually
      stimulated by the irritating action of various agents (infection, etc.). It is
      different from a radicular cyst. The definite diagnosis should be based on
      clinical, radiological, and histopathological findings. The treatment is
      enucleation of the cystic tissue, and only in rare cases a marsupialisation needs
      to be performed. A case of a nasopalatine duct cyst in a 35-year-old male is
      reviewed. The typical radiologic and histological findings are presented. 

PMID- 24307955
TI  - Porokeratotic eccrine ostial and dermal duct nevus.
AB  - PEODDN is a rare benign cutaneous disorder that clinically resembles comedo nevus
      but favors the palms and soles, where pilosebaceous follicles are absent.
      Widespread involvement along Blaschko's lines can also occur. It is a disorder of
      keratinization involving the intraepidermal eccrine duct (acrosyringium) and is
      characterized by eccrine hamartoma and cornoid lamellation in pathology. The
      patient is a 29-year-old man with an 8-year history of pruritic skin lesions on
      his right lateral ankle. In the pathologic examination, multiple small epidermal
      invagination with overlying parakeratotic cornoid lamellation, loss of granular
      layer, and few dyskeratotic cells at the base of epidermal invagination are
      revealed. After clinic-pathologic correlation, the diagnosis of porokeratotic
      eccrine ostial and dermal duct nevus (PEODDN) was made. Late-onset and rare
      clinical presentation as pruritic lesion are the characteristic features that
      make this patient an extraordinary presentation of PEODDN. 

PMID- 24307956
TI  - A novel case of functional gastric neuroendocrine carcinoma occurred after
      endoscopic submucosal dissection.
AB  - In Japan, endoscopic submucosal dissection (ESD) is becoming a standard treatment
      for intramucosal differentiated gastric cancer. Although ESD is associated with a
      high cure rate for patients with early gastric cancer, tumors may recur, albeit
      rarely. We performed ESD on an 80-year-old man with a small depressed type of
      gastric cancer of the posterior wall of the cardia, found to be locally invasive
      on histology. Thirty months later, local recurrence and multiple liver metastases
      were detected, accompanied by frequent severe hypoglycemia. Despite chemotherapy,
      the patient died 6 months after relapse. On autopsy, the recurrent gastric lesion
      and liver metastases were examined immunohistochemically. Several characteristic
      tumor cells were positive for chromogranin A, cluster of differentiation (CD) 56,
      Ki-67, and insulin-like growth factor (IGF)-II. Western blot analysis of the
      patient's serum obtained during a hypoglycemic attack showed the high molecular
      weight form of IGF-II or "big" IGF-II. The patient was diagnosed with non-islet
      cell tumor hypoglycemia (NICTH), with "big" IGF-II being produced by the gastric
      neuroendocrine carcinoma. This is the novel case of a functional gastric
      neuroendocrine carcinoma that occurred after ESD and induced a hypoglycemic
      attack associated with NICTH. 

PMID- 24307957
TI  - Mayor erythropoietic response after deferasirox treatment in a transfusion
      dependent anemic patient with primary myelofibrosis.
AB  - Primary myelofibrosis (PMF) is a myeloproliferative neoplasm frequently
      complicated by transfusion dependent anemia. Both anemia and transfusion
      dependence are associated with a poor outcome, at least in part because of toxic
      effects of iron overload (IOL). Iron-chelating therapy (ICT) is increasingly used
      in order to prevent IOL in this setting. Here, we describe the case of a 73-year
      old man affected by PMF and severe transfusion-dependent anemia who experienced a
      dramatic erythroid response after being treated with deferasirox to prevent IOL. 

PMID- 24307958
TI  - Low Molecular Weight Heparin Induced Skin Necrosis without Platelet Fall
      Revealing Immunoallergic Heparin Induced Thrombocytopenia.
AB  - Low molecular weight heparins (LMWH) are commonly used in the ICU setting for
      thromboprophylaxis as well as curative decoagulation as required during renal
      replacement therapy (RRT). A rare adverse event revealing immunoallergic LMWH
      induced thrombopenia (HIT) is skin necrosis at injection sites. We report the
      case of a patient presenting with skin necrosis witnessing an HIT after RRT,
      without thrombocytopenia. The mechanism remains unclear. Anti-PF4/heparin
      antibodies, functional tests (HIPA and/or SRA), and skin biopsy are of great help
      to evaluate differential diagnosis with a low pretest probability 4T's score. 

PMID- 24307959
TI  - Salmonella neck abscess as an opportunistic infection in diabetes mellitus.
AB  - Salmonella neck infections represent an uncommon cause of focal salmonellosis.
      While the incidence of nontyphoid salmonellosis is estimated at over 2 million
      cases annually, extraintestinal manifestations account for less than 1% of cases.
      This paper describes two patients with Salmonella neck abscesses as the initial
      presentation of diabetes mellitus. The first patient was diagnosed as having
      Salmonella enterica serotype Enteritidis sternocleidomastoid pyomyositis and the
      second patient Salmonella enterica serotype Typhimurium parapharyngeal abscess.
      Both patients had elevated hemoglobin A1c levels and had not been previously
      diagnosed with diabetes mellitus. Salmonella spp. should be on the differential
      as a causative pathogen in patients presenting with neck abscesses and poorly
      controlled glucose levels. Diabetes may be a risk factor for salmonellosis due to
      decreased gastric acidity and prolonged gastric transit time. Prompt incision and
      drainage accompanied by antibiotics remains the treatment of choice for infected
      neck abscesses. 

PMID- 24307960
TI  - Spasticity as the first manifestation of ischaemic lesions involving the
      cingulum.
AB  - Background and Purpose. Spasticity is a positive sign of upper motor neuron
      syndrome that usually develops weeks after a stroke. The mechanisms that lead to
      its appearance are not completely understood, namely, the cortical regions whose
      lesion may induce spasticity. Summary of Cases. We report two patients with an
      ischaemic stroke entailing the anterior cingulate gyrus (pericallosal artery
      territory), who presented with acute hemiplegia and spasticity since symptom
      onset. Spasticity resolved within days after onset. Conclusions. The acute
      destruction of the anterior cingulate region, interrupting inhibitory projections
      towards lower motor centres, probably explains the acute onset of spasticity that
      occurred in these two patients. Further studies addressing the role of this
      region in acute and chronic disturbances of muscular tone are necessary. 

PMID- 24307961
TI  - Hypofractionated stereotactic radiosurgery in a large bilateral thalamic and
      Basal Ganglia arteriovenous malformation.
AB  - Purpose. Arteriovenous malformations (AVMs) in the basal ganglia and thalamus
      have a more aggressive natural history with a higher morbidity and mortality than
      AVMs in other locations. Optimal treatment-complete obliteration without new
      neurological deficits-is often challenging. We present a patient with a large
      bilateral basal ganglia and thalamic AVM successfully treated with
      hypofractionated stereotactic radiosurgery (HFSRS) with intensity modulated
      radiotherapy (IMRT). Methods. The patient was treated with hypofractionated
      stereotactic radiosurgery to 30 Gy at margin in 5 fractions of 9 static fields
      with a minimultileaf collimator and intensity modulated radiotherapy. Results. At
      10 months following treatment, digital subtraction angiography showed complete
      obliteration of the AVM. Conclusions. Large bilateral thalamic and basal ganglia
      AVMs can be successfully treated with complete obliteration by HFSRS with IMRT
      with relatively limited toxicity. Appropriate caution is recommended. 

PMID- 24307962
TI  - An unexpected complete remission of advanced intestinal-type vulvar
      adenocarcinoma after neoadjuvant chemotherapy: a case report and a literature
      review.
AB  - Vulvar cancer represents approximately 3%-5% of all gynecological malignancies.
      Squamous cell carcinoma is the most frequent histotype, whereas melanomas,
      adenocarcinomas, basal cell carcinomas, and sarcomas are much less common.
      Intestinal-type adenocarcinoma is a rare variant of vulvar carcinoma with only
      few cases found in the literature. The origin of this neoplasia is still much
      debated, but the most reliable hypothesis is the origin from cloacal remnants
      that may persist in the adult in different organs. Because of its extremely low
      incidence, the optimal management of this kind of vulvar cancer is still debated.
      We report the case of a woman affected by advanced intestinal-type vulvar
      adenocarcinoma, who achieved a complete clinical and pathological response after
      neoadjuvant chemotherapeutic treatment with platinum and paclitaxel. 

PMID- 24307963
TI  - Mechanisms of L-triiodothyronine-induced inhibition of synaptosomal na(+)-k(+)
      ATPase activity in young adult rat brain cerebral cortex.
AB  - The role of thyroid hormones (TH) in the normal functioning of adult mammalian
      brain is unclear. Our studies have identified synaptosomal Na(+)-K(+)-ATPase as a
      TH-responsive physiological parameter in adult rat cerebral cortex. L
      triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na(+)-K(+)-ATPase
      activity (but not Mg(2+)-ATPase activity) in similar dose-dependent fashions,
      while other metabolites of TH were less effective. Although both T3 and the beta 
      adrenergic agonist isoproterenol inhibited Na(+)-K(+)-ATPase activity in
      cerebrocortical synaptosomes in similar ways, the beta -adrenergic receptor
      blocker propranolol did not counteract the effect of T3. Instead, propranolol
      further inhibited Na(+)-K(+)-ATPase activity in a dose-dependent manner,
      suggesting that the effect of T3 on synaptosomal Na(+)-K(+)-ATPase activity was
      independent of beta -adrenergic receptor activation. The effect of T3 on
      synaptosomal Na(+)-K(+)-ATPase activity was inhibited by the alpha2-adrenergic
      agonist clonidine and by glutamate. Notably, both clonidine and glutamate
      activate Gi-proteins of the membrane second messenger system, suggesting a
      potential mechanism for the inhibition of the effects of TH. In this paper, we
      provide support for a nongenomic mechanism of action of TH in a neuronal membrane
      related energy-linked process for signal transduction in the adult condition. 

PMID- 24307964
TI  - Poor Aerobic Fitness May Contribute to Cognitive Decline in HIV-infected Older
      Adults.
AB  - The HIV-infected older adult (HOA) community is particularly vulnerable to
      cognitive impairment. Previous studies in the general older adult population have
      reported that lower scores on tests of cognitive function often correlate
      negatively with aerobic fitness [5-7]. HIV-infected individuals have
      significantly reduced aerobic fitness and physical function compared to HIV
      uninfected individuals. Determining important correlates of cognitive ability may
      be beneficial in not only detecting precursors to future cognitive impairments,
      but also target areas for interventions. The purpose of this study was to
      investigate the relationship between cognitive ability and aerobic fitness in HIV
      infected older adults. We conducted a cross-sectional study of HOA on
      antiretroviral therapy (ART) >50 years of age. Domain specific cognitive function
      was assessed by means of a neuropsychological battery. Aerobic fitness (VO2peak)
      was assessed using a graded, progressive treadmill test. Thirty-seven HOA on ART
      (mean+/-SD: age 59+/-6 years, BMI 28+/-5, CD4 663+/-337 cells/ml, duration since
      HIV diagnosis 17+/-7 years; 81% males) completed the cognitive tests. Several
      domains of cognition were significantly associated with VO2peak by Spearman
      correlation analysis (p<0.05). By step-wise adjusted regression VO2peak was most
      frequently and significantly related to many cognitive domains such as verbal and
      visual memory, visual perception, and language (p<0.05). We found that
      participants with higher Vo2peak were less likely to have more severe forms of
      HIV-associated neurocognitive disorders (HAND) such as mild neurocognitive
      disorder (OR=0.65; p=0.01) and HIV-associated dementia (OR=0.64; p=0.0006). In
      HOA and in conclusion, aerobic fitness is related to cognitive performance on
      various tasks. The likelihood of cognitive impairment increased with lower
      fitness levels. Therefore, increased fitness may serve an important factor in
      maintenance of cognition and neural integrity for aging HIV-infected individuals.
      Future prospective and large scale studies are needed to evaluate the effect of
      fitness and vascular stiffness and function on cognition and brain structure
      among HOA. 

PMID- 24307965
TI  - Autonomic Cardiovascular Damage during Post-menopause: the Role of Physical
      Training.
AB  - Menopause is part of the aging process and is characterized by the natural
      cessation of menstruation; during this time, the production of ovarian hormones,
      especially estrogen, is sharply reduced. This reduction can cause symptoms and
      disorders that affect most women and can interfere with their quality of life.
      Women are also more susceptible to cardiovascular diseases during this period,
      considering that these ovarian hormones would be associated with a protective
      effect on the cardiovascular system, by acting at various levels, contributing to
      the body homeostasis. Among several effects on the cardiovascular system, the
      ovarian hormones seem to play an important role in the autonomic control of heart
      rate and blood pressure. A reduction in ovarian hormones causes an autonomic
      imbalance and increases the risk of cardiovascular diseases. In fact, this
      increased risk is justified by the key role the autonomic nervous system plays in
      all cardiac regulatory mechanisms, exerting a tonic and reflexive influence on
      the main variables of the cardiovascular system. The autonomic system controls
      various cardiovascular parameters, such as the modulation of heart rate and blood
      pressure, myocardial contractility and venous capacitance, directly participating
      in the regulation of cardiac output. Over the years, the standard treatment for
      menopause symptoms and disorders has been hormone replacement therapy (HRT).
      However, many studies have indicated the risks of HRT, which justify the need for
      new non-pharmacological therapies. To this end, physical training, mainly
      aerobic, has been applied with excellent results on the cardiovascular autonomic
      nervous system, as it reduces the risk of cardiac diseases and improves the
      survival rate with direct beneficial effects on the quality of life of these
      women during the aging process. 

PMID- 24307966
TI  - Depression Treatment Non-adherence and its Psychosocial Predictors: Differences
      between Young and Older Adults?
AB  - Depression is a common disease among young and older adults. Although it can be
      treated, non-adherence is very common among individuals of different ages. The
      aim of the present paper is to review and summarize research findings regarding
      depression among young and older adults, with a special focus on the phenomenon
      of treatment non-adherence among young and older adults with depression. The
      first section of the review focuses on describing the characteristics of
      depression in young and older adults. The second section focuses on treatment non
      adherence of young and older adults, the prevalence of this phenomenon, and its
      consequences. The third section focuses on several factors (illness beliefs,
      treatment beliefs, self-stigma, and self-esteem) that were identified as having a
      significant association with treatment non-adherence of individuals with
      depression, with special attention focused on age differences. Results of the
      review of the literature reveal that research in the area of depression treatment
      non-adherence and its predictors among young and older adults has received, to
      date, very minor and limited attention. Thus, there is a need to expand the
      current body of knowledge and promote future interventions geared towards the
      unique characteristics of depression among young and older adults, in order to
      increase their treatment adherence. 

PMID- 24307967
TI  - Mitochondrial DNA damage patterns and aging: revising the evidences for humans
      and mice.
AB  - A significant body of work, accumulated over the years, strongly suggests that
      damage in mitochondrial DNA (mtDNA) contributes to aging in humans. Contradictory
      results, however, are reported in the literature, with some studies failing to
      provide support to this hypothesis. With the purpose of further understanding the
      aging process, several models, among which mouse models, have been frequently
      used. Although important affinities are recognized between humans and mice,
      differences on what concerns physiological properties, disease pathogenesis as
      well as life-history exist between the two; the extent to which such differences
      limit the translation, from mice to humans, of insights on the association
      between mtDNA damage and aging remains to be established. In this paper we revise
      the studies that analyze the association between patterns of mtDNA damage and
      aging, investigating putative alterations in mtDNA copy number as well as
      accumulation of deletions and of point mutations. Reports from the literature do
      not allow the establishment of a clear association between mtDNA copy number and
      age, either in humans or in mice. Further analysis, using a wide spectrum of
      tissues and a high number of individuals would be necessary to elucidate this
      pattern. Likewise humans, mice demonstrated a clear pattern of age-dependent and
      tissue-specific accumulation of mtDNA deletions. Deletions increase with age, and
      the highest amount of deletions has been observed in brain tissues both in humans
      and mice. On the other hand, mtDNA point mutations accumulation has been clearly
      associated with age in humans, but not in mice. Although further studies, using
      the same methodologies and targeting a larger number of samples would be
      mandatory to draw definitive conclusions, the revision of the available data
      raises concerns on the ability of mouse models to mimic the mtDNA damage patterns
      of humans, a fact with implications not only for the study of the aging process,
      but also for investigations of other processes in which mtDNA dysfunction is a
      hallmark, such as neurodegeneration. 

PMID- 24307970
TI  - Is bilateral orchiectomy for metastatic prostate cancer treatment associated with
      high cardiovascular risk?
AB  - Cardiovascular disease is one of the most common causes of death worldwide and
      the most usual in the western populations. Although it affects both sexes, it is
      more frequent in males in whom it shortens the average life expectancy. This
      difference has been attributed to the negative effects of testosterone; however,
      recent research showed that this hormone may have protective effects on the
      cardiovascular system. In confirmation to the above current evidence suggests
      that the low levels of testosterone could be associated with an increased CVD
      risk and with an augmentation of morbidity and mortality in males. In the present
      article, we present 2 cases of men with CVD and metastatic prostate cancer
      treated with bilateral orchiectomy who died of acute stroke during the
      perioperational period. The possible association of androgen deprivation with
      cardiovascular disease progression and the consequent risk of stroke are briefly
      discussed. 

PMID- 24307971
TI  - Perioperative Pain Management for Patients on Chronic Buprenorphine: A Case
      Report.
AB  - Here we present a patient with a Type I Chiari malformation who was receiving
      buprenorphine for chronic pain who underwent two separate urogynecologic
      procedures for removal of vaginal mesh with two different pain management
      regimens. For the first procedure at an outside hospital, the patient's usual
      dose of buprenorphine (8 mg sublingual every 8 hours) was continued up through
      her surgery and then a full opioid receptor agonist was used for postoperative
      pain management. The patient complained that this resulted in very poor pain
      control for her in the postoperative period. Prior to her second procedure, which
      was performed at our institution, buprenorphine was switched to a full opioid
      agonist (oral hydromorphone 4 mg every 4 to 6 hours, maximum 20 mg per day) for 5
      days prior to surgery; postoperative pain was managed with full opioid receptor
      agonists. The patient again reported suboptimal pain control in spite of
      substantially increased doses of opioids. This case report highlights the
      difficulty of perioperative pain management for patients on chronic buprenorphine
      and emphasizes the need for additional investigation.

PMID- 24307968
TI  - Aging, functional capacity and eccentric exercise training.
AB  - Aging is a multi-factorial process that ultimately induces a decline in our
      physiological functioning, causing a decreased health-span, quality of life and
      independence for older adults. Exercise participation is seen as a way to reduce
      the impact of aging through maintenance of physiological parameters. Eccentric
      exercise is a model that can be employed with older adults, due to the muscle's
      ability to combine high muscle force production with a low energy cost. There may
      however be a risk of muscle damage before the muscle is able to adapt. The first
      part of this review describes the process of aging and how it reduces aerobic
      capacity, muscle strength and therefore functional mobility. The second part
      highlights eccentric exercise and the associated muscle damage, in addition to
      the repeated bout effect. The final section reviews eccentric exercise
      interventions that have been completed by older adults with a focus on the
      changes in functional mobility. In conclusion, eccentric endurance exercise is a
      potential training modality that can be applied to older adults for improving
      muscle strength, aerobic capacity and functional ability. However, further
      research is needed to assess the effects on aerobic capacity and the ideal
      prescription for eccentric endurance exercise. 

PMID- 24307969
TI  - mtDNA Mutations and Their Role in Aging, Diseases and Forensic Sciences.
AB  - Mitochondria are independent organelles with their own DNA. As a primary
      function, mitochondria produce the energy for the cell through Oxidative
      Phosphorylation (OXPHOS) in the Electron Transport Chain (ETC). One of the toxic
      products of this process is Reactive Oxygen Species (ROS), which can induce
      oxidative damage in macromolecules like lipids, proteins and DNA. Mitochondrial
      DNA (mtDNA) is less protected and has fewer reparation mechanisms than nuclear
      DNA (nDNA), and as such is more exposed to oxidative, mutation-inducing damage.
      This review analyzes the causes and consequences of mtDNA mutations and their
      relationship with the aging process. Neurodegenerative diseases, related with the
      aging, are consequences of mtDNA mutations resulting in a decrease in
      mitochondrial function. Also described are "mitochondrial diseases", pathologies
      produced by mtDNA mutations and whose symptoms are related with mitochondrial
      dysfunction. Finally, mtDNA haplogroups are defined in this review; these groups
      are important for determination of geographical origin of an individual.
      Additionally, different haplogroups exhibit variably longevity and risk of
      certain diseases. mtDNA mutations in aging and haplogroups are of special
      interest to forensic science research. Therefore this review will help to clarify
      the key role of mtDNA mutations in these processes and support further research
      in this area. 

PMID- 24307972
TI  - Improved biomarker performance for the detection of hepatocellular carcinoma by
      inclusion of clinical parameters.
AB  - We have previously identified several biomarkers of hepatocellular carcinoma
      (HCC). The levels of three of these biomarkers were analyzed individually and in
      combination with the currently used marker, alpha fetoprotein (AFP), for the
      ability to distinguish between a diagnosis of cirrhosis (n=113) and HCC (n=164).
      We have utilized several novel biostatistical tools, along with the inclusion of
      clinical factors such as age and gender, to determine if improved algorithms
      could be used to increase the probability of cancer detection. Using several of
      these methods, we are able to detect HCC in the background of cirrhosis with an
      AUC of at least 0.95. The use of clinical factors in combination with biomarker
      values to detect HCC is discussed.

PMID- 24307974
TI  - A case of paranoid schizophrenia and severe antipsychotic-induced Parkinson's
      disorder treated with a combination of olanzapine and lurasidone.

PMID- 24307975
TI  - Posttraumatic stress disorder exacerbation with cholinesterase inhibitor in a
      patient with dementia.

PMID- 24307976
TI  - The demographics of pain catastrophizing in a primary care sample.

PMID- 24307973
TI  - Human Umbilical Cord Blood for Transplantation Therapy in Myocardial Infarction.
AB  - Cell-based therapy is a promising therapy for myocardial infarction. Endogenous
      repair of the heart muscle after myocardial infarction is a challenge because
      adult cardiomyocytes have a limited capacity to proliferate and replace damaged
      cells. Pre-clinical and clinical evidence has shown that cell based therapy may
      promote revascularization and replacement of damaged myocytes after myocardial
      infarction. Adult stem cells can be harvested from different sources including
      bone marrow, skeletal myoblast, and human umbilical cord blood cells. The use of
      these cells for the repair of myocardial infarction presents various advantages
      over other sources of stem cells. Among these are easy harvesting, unlimited
      differentiation capability, and robust angiogenic potential. In this review, we
      discuss the milestone findings and the most recent evidence demonstrating the
      therapeutic efficacy and safety of the transplantation of human umbilical cord
      blood cells as a stand-alone therapy or in combination with gene therapy,
      highlighting the importance of optimizing the timing, dose and delivery methods,
      and a better understanding of the mechanisms of action that will guide the
      clinical entry of this innovative treatment for ischemic disorders, specifically
      myocardial infarction.

PMID- 24307977
TI  - A pilot study evaluating genetic and environmental factors for postpartum
      depression.
AB  - OBJECTIVE: To assess the influence of genetic and environmental risk factors upon
      postpartum depression. DESIGN: Case-control, prospective study. SETTING: The
      University of California at San Francisco Obstetric and Gynecology Clinic.
      PARTICIPANTS: Mothers screened for postpartum depression six weeks after delivery
      with the Edinburgh Postnatal Depression Scale and recruited as cases and
      controls. MEASUREMENTS: Eligible subjects completed a series of assessments and a
      structured clinical interview to confirm diagnosis of depression.
      Deoxyribonucleic acid was obtained for genotyping of 81 single nucleotide
      polymorphisms in 12 genes hypothesized to be postpartum depression-related.
      RESULTS: Twenty-four cases and 24 controls were eligible for analysis. Three
      single necleotide polymorphisms in the serotonin 2A receptor (HTR2A) gene were
      associated with postpartum depression. The strongest association at a functional
      promoter polymorphism (rs6311), a functional promoter single nucleotide
      polymorphisms (p=0.002, odds ratio 0.25, 95% confidence interval:0.10-0.63), was
      a finding robust to population stratification. Gene-wide association was
      significant for HTR2A (permuted p=0.008), but not when corrected for all 12
      genes. Analysis of demographic and psychosocial risk factors identified
      distressed relationship, unplanned pregnancy, and a previous history of
      depression as significant predictive variables (p<=0.05). CONCLUSIONS: This pilot
      data suggests deoxyribonucleic acid variations in HTR2A may be associated with
      postpartum depression. Psychosocial variables were also identified as risk
      factors. The relative influence of these variables on the manifestation of
      postpartum depression is yet to be determined.

PMID- 24307978
TI  - Differential diagnosis of hallucinations in a patient with myasthenia gravis.
AB  - We present the case of a 63-year-old woman with comorbidity of myasthenia gravis
      and psychosis. Different diagnostic hypotheses based on a review of the
      literature are discussed. A protracted history of physical spousal abuse, patient
      symptoms, and results of different investigations allowed us to conclude that the
      patient had a form of posttraumatic stress disorder with secondary psychotic
      features. Psychosis due to myasthenia gravis is rarely seen, and it remains
      unclear what is the pathophysiology, if any, for such an association. The present
      case highlights the difficulties the physician faces in disentangling psychosis
      as a potential manifestation of myasthenia gravis itself versus being caused by a
      medical side effect of treatment, or psychosis due to a distinct co-occurring
      neurologic or psychiatric condition. 

PMID- 24307979
TI  - A Case of Reversible Neuropsychiatry Symptoms in HIV due to Toxic
      Leukoencephalopathy.
AB  - Mothball ingestion has been previously cited to induce toxic-leukoencephalopathy,
      secondary to the destructive effects of paradichlorobenzene on central nervous
      system white matter. This case presents a 37-year-old woman who experienced a
      neuropsychiatric syndrome consistent with paradichlorobenzene-induced toxic
      leukoencephalopathy after two decades of mothball abuse. Her clinical
      presentation was insidious, involving fluctuating cognitive decline, depression,
      and psychosis. This was further complicated by an human immunodeficiency virus
      infection and concomitant cocaine abuse. Ultimately, her clinical findings were
      attributed to a reversible toxic-leukoencephalopathy from mothball ingestion, and
      her magnetic resonance imaging findings were consistent with symmetric
      leukoencephalopathy and atrophy. Though leukoencephalopathy in human
      immunodeficiency virus has numerous potential etiologies, a patient with a
      history of substance abuse warrants consideration of toxin-induced
      leukoencephalopathy, and further inquiry regarding abuse of other substances is
      appropriate. 

PMID- 24307980
TI  - Obesity and substance misuse: is there a relationship?
AB  - The relationship between obesity and alcohol/drug misuse has been examined
      through both site studies and large epidemiological studies. In reviewing 19 site
      studies that have examined alcohol misuse among the obese, in comparison with
      rates before 1990, rates since 1990 have doubled (6.2% to 14.3%). Of the 7
      studies that have examined drug misuse among the obese, rates average 8.0%. Given
      the potential limitations of varying study populations, methodologies, and
      prevalence assessments, these rates closely reflect those in the general
      population, according to data from the National Comorbidity Survey Replication
      study. As for the findings from 5 large epidemiological studies, Overall,
      findings do not clearly support the contention that obese individuals are at a
      higher risk for substance misuse, although specific sub-populations of the obese
      may be (e.g., those with Cluster B personality disorders). If there is an
      association between some obese populations and substance abuse, this may be
      accounted for by overlapping neurohormonal correlates. However, some authorities
      contend that food and drugs compete for the same reward pathways in the brain,
      suggesting that obesity may actually be protective against substance misuse. 

PMID- 24307981
TI  - Pubertal pathways and the relationship to anthropometric changes in childhood:
      The Fels longitudinal study.
AB  - OBJECTIVE: To examine the relationship of the initial manifestation of pubertal
      development in children to anthropometric measurements recorded during the early
      childhood and adolescence. METHODS: The Fels Longitudinal study is an
      observational study of growth and development of healthy white children. A total
      of 109 boys and 75 girls with serial self-assessments of Tanner stages of
      genital/breast and pubic hair developments provided data for a longitudinal
      analysis with a linear mixed model. RESULTS: About 11.0% of boys and 22.7% of
      girls witnessed the appearance of pubic hair (adrenarche) prior to the onset of
      genital/breast growth (gonadarche/thelarche) and about 13.7% of boys and 22.7% of
      girls experienced the onset of gonadarche/thelarche prior to adrenarche. The
      remaining 75.3% of boys and 54.7% of girls were concordant for adrenarche and
      gonadarche/thelarche. During the first two years of life, boys and girls with
      earlier gonadarche and thelarche than adrenarche were found to have more rapid
      weight gain than those with earlier adrenarche than gonadarche/thelarche. During
      early childhood from age 2 - 7 years, those girls with early thelarche had higher
      body mass index (BMI) and waist circumference to height ratio (waist/height) than
      those with early adrenarche. In children of ages 8 - 20, girls with early
      gonadarche had higher BMI z-scores than those with early adrenarche. CONCLUSION:
      Girls with early thelarche and later adrenarche, have more rapid mean weight gain
      during the first two years of life, higher BMI and waist/height during early
      childhood, and higher BMI z-scores during adolescence. Boys with early gonadarche
      and later adrenarche experienced more rapid weight gain during the first two
      years of life than boys with early adrenarche and later gonadarche. In other
      words, girls with early thelarche are more likely to be triggered by early
      accumulation of fat mass than those with early adrenarche.

PMID- 24307982
TI  - Fruit intake associated with urinary estrogen metabolites in healthy
      premenopausal women.
AB  - Urinary concentrations of 2:16-hydroxyestrone (2:16-OHE1) approximate
      concentrations of 2-OHE1 and 16alpha -OHE1 in breast tissue. As estrogens are
      purported to be involved in breast cancer development, the 2:16-OHE1 ratio can
      provide an indication of estrogen metabolite exposure in the breast. With prior
      studies observing associations between urinary estrogen metabolites and dietary
      intake of fruits, vegetables, and fiber ascertained from food questionnaires, we
      examined associations between dietary factors ascertained through 3-day food
      records and urinary 2:16-OHE1 in 191 pre-menopausal healthy women. Fruit
      consumption was positively associated with 2:16-OHE1 after adjustment for total
      energy, ethnicity, body mass index, parity, smoking history, and serum estradiol
      (p= 0.003). Fruit consumption was positively associated with 2- OHE1
      concentrations (p=0.006), but was not associated with 16alpha-OHE1 (p=0.92). The
      Musaceae botanical grouping (comprised primarily of bananas) was positively
      associated with the 2:16-OHE1 ratio, and Rosaceae (comprised of citrus fruits)
      and Musaceae botanical groupings were positively associated with 2-OHE1 (but not
      16alpha-OHE1) concentrations, after adjustment for confounders. Our data suggest
      that dietary fruit intake is associated with urinary 2- OHE1 and the 2:16-OHE1
      ratio and that breast tissue exposure to estrogen metabolites may thus be
      influenced by diet.

PMID- 24307983
TI  - Patient eligibility criteria for a surgical treatment that enhances tissue
      sealing by use of a medicated sponge: observational study ELITE.
AB  - RATIONALE: The application of a haemostatic agent in general surgery, in addition
      to its effect on bleeding, also provides tissue sealing and adhesion. A sponge
      drug is used with some actions of resection and wide dissection, without
      knowledge of the eligibility of patients. In this study, we sought to identify
      clusters of patients for which the medicated sponge enhances tissue sealing.
      METHODS: Observational study (ELITE), from a panel of selected surgeons from
      hospitals in France in several surgical areas: abdominal, gynaecology, urology
      and thoracic. The survey identified the criteria for using the sponge TachoSil(r)
      in their surgical practices involving n = 683 patients. A multiple correspondence
      analysis (MCA) followed by an ascending hierarchical classification (AHC) was
      used in order to identify the eligibility criteria for the application of the
      sponge for tissue sealing in addition to hemostasis. RESULTS: The most relevant
      classification was based on 9 groups of patients for which the sponge was used. 6
      of them are mainly linked with the kind of lesion, 2 with the site of application
      and the latest one with the type of operation. CONCLUSIONS: The ELITE study
      revealed that the TachoSil(r) sponge was used mainly during surgery, requiring a
      reinforcement of the resection tissue sealing. The expected objective was
      successfully reached in 97% of the cases.

PMID- 24307984
TI  - A reliable and effective method of DNA isolation from old human blood paper
      cards.
AB  - Blood paper cards provide an effective DNA storage method. In this study, we used
      three DNA dissolving reagents (Tris-EDTA [TE] buffer, Tris-HCl buffer, and water)
      and one common commercially available kit (DN131 from MRC Inc) to elute DNA from
      105 human blood paper cards collected up to 10 years ago. These DNA samples were
      used as templates for amplification of a single nucleotide polymorphism (SNP,
      C125T) region of human caspase-12 by PCR and a specific Taqman genotyping assay
      using the same amount of DNA. We show that DNA isolated by Tris-HCl buffer has
      higher yield and quality in comparison to DN131 solution. PCR success rate to
      amplify caspase-12 C125T SNP using Tris-HCl is comparable to the method using
      DN131 (89.5% vs 87.6%). The Taqman genotyping success rate using Tris-HCl is
      higher than using DN131 (81.9% vs 70.5%). Using TE or water, PCR success rates
      are lower than using DN131 (73.3% [TE]; 72.4% [H2O]), but Taqman genotyping
      success rates are comparable to the method using DN131 (70.5% [TE]; 79.1% [H2O]).
      We concluded that using Tris-HCl is a reliable and effective method to elute DNA
      from old human blood paper cards. The crude DNA isolated by Tris-HCl can be used
      to study genetic polymorphisms in human populations. 

PMID- 24307985
TI  - Exact traveling wave solutions of the KP-BBM equation by using the new approach
      of generalized (G'/G)-expansion method.
AB  - The new approach of the generalized (G'/G)-expansion method is an effective and
      powerful mathematical tool in finding exact traveling wave solutions of nonlinear
      evolution equations (NLEEs) in science, engineering and mathematical physics. In
      this article, the new approach of the generalized (G'/G)-expansion method is
      applied to construct traveling wave solutions of the Kadomtsev-Petviashvili
      Benjamin-Bona-Mahony (KP-BBM) equation. The solutions are expressed in terms of
      the hyperbolic functions, the trigonometric functions and the rational functions.
      By means of this scheme, we found some new traveling wave solutions of the above
      mentioned equation. 

PMID- 24307986
TI  - Impact of freezing rate on electrical conductivity of produce.
AB  - The aim of this work was to compare the effects of freezing rate on electrical
      conductivity of potatoes, carrots and apples. Electrical conductivity tests were
      conducted on a custom ohmic cell while samples texture was measured by means of a
      universal testing machine. The raw un-pretreated samples were used as control.
      This study showed that freezing pre-treatments lead to differences in electrical
      conductivity of considered samples, producing structural damage, the latter being
      relatively more severe when the tested products undergo ohmic treatment. 

PMID- 24307987
TI  - Effectiveness and safety of intensive triplet chemotherapy plus bevacizumab, FIr
      B/FOx, in young-elderly metastatic colorectal cancer patients.
AB  - Four-drug regimens, such as FIr-B/FOx schedule, can improve efficacy of first
      line treatment of metastatic colorectal cancer (MCRC) patients. The present study
      specifically evaluates feasibility of FIr-B/FOx first-line intensive regimen in
      fit young-elderly MCRC patients, representing approximately 40% of overall MCRC
      patients. Activity, efficacy, and safety were equivalent to overall MCRC
      patients, not significantly different according to KRAS genotype. Clinical
      outcome was significantly prolonged in liver-limited compared to other/multiple
      metastatic disease. Safety evaluation of the individual young-elderly patient
      showed that limiting toxicity syndromes (LTS) in multiple sites were
      significantly increased, compared to LTS in single site, with respect to non
      elderly patients. 

PMID- 24307988
TI  - The hidden burden of trichinellosis in Vietnam: a postoutbreak epidemiological
      study.
AB  - A cross-sectional study was conducted in Muong Lat town (Thanh Hoa province,
      North Vietnam), following the confirmed diagnosis of trichinellosis in six
      patients from that town who had eaten hunted wild boar meat during the Vietnamese
      lunar year celebration. All inhabitants who declared to have eaten undercooked or
      raw wild boar meat at the celebration and showed at least one clinical symptom
      compatible with trichinellosis were included in the study and blood sampled. Anti
      Trichinella IgG were determined by ELISA and Western Blot. Seropositive persons
      were given appropriate albendazole treatment and were followed up. A total of 100
      inhabitants met the inclusion criteria. Among these, 30 (30%) had antibodies to
      Trichinella. Serologically confirmed cases had fever (90.0%), myalgia (86.7%),
      facial oedema (63.3%), diarrhoea (53.3%), and pain of the masseter muscles
      (43.3%). Eosinophilia was detected in 83.3% of these individuals. Clinical
      symptoms resolved in all patients during albendazole treatment. The results
      suggest that only a proportion of the trichinellosis cases had sought health care
      during the outbreak. There is a need to implement surveillance and better
      diagnosis for trichinellosis and to set up educational programs to prevent
      infection in North Vietnam. 

PMID- 24307989
TI  - S100A12 and hBD2 correlate with the composition of the fecal microflora in ELBW
      infants and expansion of E. coli is associated with NEC.
AB  - OBJECTIVE: To describe the development of the gut microbiota in extremely low
      birth weight (ELBW) infants with and without necrotizing enterocolitis (NEC)
      between April 2008 and December 2009, fecal microflora was prospectively analyzed
      in fecal samples of all ELBW infants using real-time PCR assays. In addition,
      fecal inflammatory were measured. RESULTS: Fecal microflora established early in
      ELBW infants and microbiota composition remained stable over the first 28 days of
      life except for the prevalence of C. difficile which decreased with decreasing
      antibiotic use. Infants who subsequently developed NEC had an increase of total
      bacterial count (9.8-fold) 24 h prior to clinical symptoms mainly due to the
      expansion of E. coli species (21.6-fold), whereas microbiota composition did not
      differ from healthy ELBW infants five days before onset of NEC. Importantly,
      S100A12 and hBD2 positively correlated with the total and E. coli bacterial CFU/g
      feces (r (2) 0.4 and 0.64, resp.). CONCLUSIONS: In summary, we found evidence for
      a disturbed homeostasis between the intestinal microbiome and host immunity in
      ELBW infants with NEC. Moreover, S100A12 and hBD2 correlate with the fecal
      microbiota thus linking the intestinal innate immune response to the bacterial
      colonization thus possibly providing a diagnostic tool in the future.

PMID- 24307990
TI  - Thermal and chemical stability of two homologous POZ/BTB domains of KCTD proteins
      characterized by a different oligomeric organization.
AB  - POZ/BTB domains are widespread modules detected in a variety of different
      biological contexts. Here, we report a biophysical characterization of the
      POZ/BTB of KCTD6, a protein that is involved in the turnover of the muscle small
      ankyrin-1 isoform 5 and, in combination with KCTD11, in the ubiquitination and
      degradation of HDAC1. The analyses show that the domain is a tetramer made up by
      subunits with the expected alpha /beta structure. A detailed investigation of its
      stability, carried out in comparison with the homologous pentameric POZ/BTB
      domain isolated from KCTD5, highlights a number of interesting features, which
      are shared by the two domains despite their different organization. Their
      thermal/chemical denaturation curves are characterized by a single and sharp
      inflection point, suggesting that the denaturation of the two domains is a
      cooperative two-state process. Furthermore, both domains present a significant
      content of secondary structure in their denatured state and a reversible
      denaturation process. We suggest that the ability of these domains to fold and
      unfold reversibly, a property that is somewhat unexpected for these oligomeric
      assemblies, may have important implications for their biological function.
      Indeed, these properties likely favor the formation of heteromeric associations
      that may be essential for the intricate regulation of the processes in which
      these proteins are involved. 

PMID- 24307991
TI  - Sympathomimetic activity of a Hoodia gordonii product: a possible mechanism of
      cardiovascular side effects.
AB  - Hoodia gordonii, a popular appetite suppressant, is widely used as an ingredient
      in many food supplements despite the fact that supporting scientific evidence is
      scarce. Recently alarming side effects of H. gordonii products (increased blood
      pressure and elevated pulse rate) have been reported. The aim of our study was to
      elucidate the underlying mechanism of these symptoms. A H. gordonii-containing
      product was tested for sympathomimetic activity. Isolated organ experiments on
      rat uterine rings revealed smooth muscle relaxant effect with a substantial
      component mediated through beta -adrenergic receptors. Chromatographic comparison
      of the analyzed product and authentic plant material confirmed that the herbal
      product contained Hoodia spp. extract, and its cardiovascular effects may be
      linked to the compounds of the plant. 

PMID- 24307992
TI  - A machine-learned predictor of colonic polyps based on urinary metabolomics.
AB  - We report an automated diagnostic test that uses the NMR spectrum of a single
      spot urine sample to accurately distinguish patients who require a colonoscopy
      from those who do not. Moreover, our approach can be adjusted to tradeoff between
      sensitivity and specificity. We developed our system using a group of 988
      patients (633 normal and 355 who required colonoscopy) who were all at average or
      above-average risk for developing colorectal cancer. We obtained a metabolic
      profile of each subject, based on the urine samples collected from these
      subjects, analyzed via (1)H-NMR and quantified using targeted profiling. Each
      subject then underwent a colonoscopy, the gold standard to determine whether
      he/she actually had an adenomatous polyp, a precursor to colorectal cancer. The
      metabolic profiles, colonoscopy outcomes, and medical histories were then
      analysed using machine learning to create a classifier that could predict whether
      a future patient requires a colonoscopy. Our empirical studies show that this
      classifier has a sensitivity of 64% and a specificity of 65% and, unlike the
      current fecal tests, allows the administrators of the test to adjust the tradeoff
      between the two. 

PMID- 24307993
TI  - Hippuric acid as a significant regulator of supersaturation in calcium oxalate
      lithiasis: the physiological evidence.
AB  - At present, the clinical significance of existing physicochemical and biological
      evidence and especially the results we have obtained from our previous in vitro
      experiments have been analyzed, and we have come to the conclusion that hippuric
      acid (C6H5CONHCH2COOH) is a very active solvent of Calcium Oxalate (CaOX) in
      physiological solutions. Two types of experiments have been discussed: clinical
      laboratory analysis on the urine excretion of hippuric acid (HA) in patients with
      CaOX lithiasis and detailed measurements of the kinetics of the dissolution of
      CaOX calculi in artificial urine, containing various concentrations of HA. It
      turns out that the most probable value of the HA concentration in the control
      group is approximately ten times higher than the corresponding value in the group
      of the stone-formers. Our in vitro analytical measurements demonstrate even a
      possibility to dissolve CaOX stones in human urine, in which increased
      concentration of HA have been established. A conclusion can be that drowning out
      HA is a significant regulator of CaOX supersaturation and thus a regulation of
      CaOX stone formation in human urine. Discussions have arisen to use increased
      concentration of HA in urine both as a solubilizator of CaOX stones in the
      urinary tract and on the purpose of a prolonged metaphylactic treatment. 

PMID- 24307994
TI  - Enzymes inhibition and antidiabetic effect of isolated constituents from Dillenia
      indica.
AB  - AIMS: This study was designed to investigate the enzyme inhibitory and
      antidiabetic activity for the constituents isolated from Dillenia indica.
      METHODS: The leaves of D. indica were extracted with methanol and subjected to
      fractionation and chromatographic separation, which led to the isolation of seven
      compounds: betulinic acid (1), n-heptacosan-7-one (2), n-nonatriacontan-18-one
      (3), quercetin (4), beta sitosterol (5), stigmasterol (6), and stigmasteryl
      palmitate (7). Among these isolates, compounds 1, 4, 5, and 6 were evaluated for
      in vitro enzyme inhibition and compounds 4, 5 and 6 were evaluated for
      antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice.
      RESULTS: Compounds 1, 4, 5, and 6 showed 47.4, 55.2, 48.8, and 44.3% alpha 
      amylase inhibition, respectively, and 52.2, 78.2, 52.5, and 34.2% alpha 
      glucosidase inhibition, respectively, at the dose of 50 ug/kg. Compounds 4, 5 and
      6 also showed significant (*P < 0.05) antidiabetic activity in streptozotocin
      nicotinamide induced diabetic mice at the dose of 10 mg/kg. CONCLUSION: These
      results provide evidence that Dillenia indica might be a potential source of
      antidiabetic agents.

PMID- 24307995
TI  - A combination of radiosurgery and soluble tissue factor enhances vascular
      targeting for experimental glioblastoma.
AB  - Radiosurgery for glioblastoma is limited to the development of resistance,
      allowing tumor cells to survive and initiate tumor recurrence. Based on our
      previous work that coadministration of tissue factor and lipopolysaccharide
      following radiosurgery selectively induced thrombosis in cerebral arteriovenous
      malformations, achieving thrombosis of 69% of the capillaries and 39% of medium
      sized vessels, we hypothesized that a rapid and selective shutdown of the
      capillaries in glioblastoma vasculature would decrease the delivery of oxygen and
      nutrients, reducing tumor growth, preventing intracranial hypertension, and
      improving life expectancy. Glioblastoma was formed by implantation of GL261 cells
      into C57Bl/6 mouse brain. Mice were intravenously injected tissue factor,
      lipopolysaccharide, a combination of both, or placebo 24 hours after
      radiosurgery. Control mice received both agents after sham irradiation.
      Coadministration of tissue factor and lipopolysaccharide led to the formation of
      thrombi in up to 87 +/- 8% of the capillaries and 46 +/- 4% of medium sized
      vessels within glioblastoma. The survival rate of mice in this group was 80%
      versus no survivor in placebo controls 30 days after irradiation. Animal body
      weight increased with time in this group (r = 0.88, P = 0.0001). Thus,
      radiosurgery enhanced treatment with tissue factor, and lipopolysaccharide
      selectively induces thrombosis in glioblastoma vasculature, improving life
      expectancy.

PMID- 24307996
TI  - 17 beta -Estradiol attenuates poststroke depression and increases neurogenesis in
      female ovariectomized rats.
AB  - Studies have linked neurogenesis to the beneficial actions of specific
      antidepressants. However, whether 17 beta -estradiol (E2), an antidepressant, can
      ameliorate poststroke depression (PSD) and whether E2-mediated improvement of PSD
      is associated with neurogenesis are largely unexplored. In the present study, we
      found that depressive-like behaviors were observed at the first week after focal
      ischemic stroke in female ovariectomized (OVX) rats, as measured by sucrose
      preference and open field test, suggesting that focal cerebral ischemia could
      induce PSD. Three weeks after middle cerebral artery occlusion (MCAO), rats were
      treated with E2 for consecutive 14 days. We found that E2-treated rats had
      significantly improving ischemia-induced depression-like behaviors in the forced
      swimming test and sucrose preference test, compared to vehicle-treated group. In
      addition, we also found that BrdU- and doublecortin (DCX)-positive cells in the
      dentate gyrus of the hippocampus and the subventricular zone (SVZ) were
      significantly increased in ischemic rats after E2 treatment, compared to vehicle
      treated group. Our data suggest that focal cerebral ischemia can induce PSD, and
      E2 can ameliorate PSD. In addition, newborn neurons in the hippocampus may play
      an important role in E2-mediated antidepressant like effect after ischemic
      stroke. 

PMID- 24307999
TI  - Back propagation neural network model for predicting the performance of
      immobilized cell biofilters handling gas-phase hydrogen sulphide and ammonia.
AB  - Lab scale studies were conducted to evaluate the performance of two
      simultaneously operated immobilized cell biofilters (ICBs) for removing hydrogen
      sulphide (H2S) and ammonia (NH3) from gas phase. The removal efficiencies (REs)
      of the biofilter treating H2S varied from 50 to 100% at inlet loading rates
      (ILRs) varying up to 13 g H2S/m(3) .h, while the NH3 biofilter showed REs ranging
      from 60 to 100% at ILRs varying between 0.5 and 5.5 g NH3/m(3) .h. An application
      of the back propagation neural network (BPNN) to predict the performance
      parameter, namely, RE (%) using this experimental data is presented in this
      paper. The input parameters to the network were unit flow (per min) and inlet
      concentrations (ppmv), respectively. The accuracy of BPNN-based model predictions
      were evaluated by providing the trained network topology with a test dataset and
      also by calculating the regression coefficient (R (2)) values. The results from
      this predictive modeling work showed that BPNNs were able to predict the RE of
      both the ICBs efficiently.

PMID- 24307998
TI  - CX3CR1 receptor polymorphisms, Th1 cell recruitment, and acute myocardial
      infarction outcome: looking for a link.
AB  - Fractalkine is a proinflammatory chemokine that participates in atherosclerotic
      process mediating the interactions of vascular cells and leukocytes and selective
      recruitment of Th1 lymphocytes, through interaction with CX3CR1 receptor. The
      polymorphism of the fractalkine receptor 280M-containing haplotype, which
      codifies for a receptor with minor expression and with a reduced binding
      capability, represents a novel protective factor of atherosclerotic disease. We
      investigated the association among CX3CR1 genotype, the inflammatory infiltrate
      subpopulations recruited in the plaque, and the in situ expression of fractalkine
      and its receptor, in patients who died of myocardial infarction (AMI) compared
      with subjects who died of noncardiac causes. Patients with nonlethal AMI (AMI
      survivors) were also investigated to correlate the CX3CR1 polymorphisms and the
      incidence of lethal AMI. A strong T cells infiltrate was found in infarct related
      artery (IRA) plaques of AMI patients presenting the V249 T280 haplotype (84%).
      Conversely, a decreased T cell recruitment was associated with I249T280 haplotype
      in the controls (64%). The significant higher presence of the variant allele I249
      in homo- and heterozygosis, found in controls (91%) and in AMI survivors (94%),
      with respect to the patients who died of AMI (48%), showed the relevance of this
      polymorphism both in the onset and outcome of acute myocardial infarction. The
      presence of CX3CR1 polymorphisms could influence the incidence and the outcome of
      acute myocardial infarction, altering the inflammation of the whole coronary tree
      by the impaired recruitment of Th1 polarized subpopulation in the coronary
      plaque. 

PMID- 24308000
TI  - ASPic-GeneID: a lightweight pipeline for gene prediction and alternative isoforms
      detection.
AB  - New genomes are being sequenced at an increasingly rapid rate, far outpacing the
      rate at which manual gene annotation can be performed. Automated genome
      annotation is thus necessitated by this growth in genome projects; however, full
      fledged annotation systems are usually home-grown and customized to a particular
      genome. There is thus a renewed need for accurate ab initio gene prediction
      methods. However, it is apparent that fully ab initio methods fall short of the
      required level of sensitivity and specificity for a quality annotation. Evidence
      in the form of expressed sequences gives the single biggest improvement in
      accuracy when used to inform gene predictions. Here, we present a lightweight
      pipeline for first-pass gene prediction on newly sequenced genomes. The two main
      components are ASPic, a program that derives highly accurate, albeit not
      necessarily complete, EST-based transcript annotations from EST alignments, and
      GeneID, a standard gene prediction program, which we have modified to take as
      evidence intron annotations. The introns output by ASPic CDS predictions is given
      to GeneID to constrain the exon-chaining process and produce predictions
      consistent with the underlying EST alignments. The pipeline was successfully
      tested on the entire C. elegans genome and the 44 ENCODE human pilot regions. 

PMID- 24307997
TI  - Adipose-derived mesenchymal cells for bone regereneration: state of the art.
AB  - Adipose tissue represents a hot topic in regenerative medicine because of the
      tissue source abundance, the relatively easy retrieval, and the inherent
      biological properties of mesenchymal stem cells residing in its stroma. Adipose
      derived mesenchymal stem cells (ASCs) are indeed multipotent somatic stem cells
      exhibiting growth kinetics and plasticity, proved to induce efficient tissue
      regeneration in several biomedical applications. A defined consensus for their
      isolation, classification, and characterization has been very recently achieved.
      In particular, bone tissue reconstruction and regeneration based on ASCs has
      emerged as a promising approach to restore structure and function of bone
      compromised by injury or disease. ASCs have been used in combination with
      osteoinductive biomaterial and/or osteogenic molecules, in either static or
      dynamic culture systems, to improve bone regeneration in several animal models.
      To date, few clinical trials on ASC-based bone reconstruction have been concluded
      and proved effective. The aim of this review is to dissect the state of the art
      on ASC use in bone regenerative applications in the attempt to provide a
      comprehensive coverage of the topics, from the basic laboratory to recent
      clinical applications. 

PMID- 24308001
TI  - Biocompatibility assessment of novel collagen-sericin scaffolds improved with
      hyaluronic Acid and chondroitin sulfate for cartilage regeneration.
AB  - Cartilage tissue engineering (CTE) applications are focused towards the use of
      implantable biohybrids consisting of biodegradable scaffolds combined with in
      vitro cultured cells. Hyaluronic acid (HA) and chondroitin sulfate (CS) were
      identified as the most potent prochondrogenic factors used to design new
      biomaterials for CTE, while human adipose-derived stem cells (ASCs) were proved
      to display high chondrogenic potential. In this context, our aim was not only to
      build novel 3D porous scaffolds based on natural compounds but also to evaluate
      their in vitro biological performances. Therefore, for prospective CTE, collagen
      sericin (Coll-SS) scaffolds improved with HA (5% or 10%) and CS (5% or 10%) were
      used as temporary physical supports for ASCs and were analyzed in terms of
      structural, thermal, morphological, and swelling properties and cytotoxic
      potential. To complete biocompatibility data, ASCs viability and proliferation
      potential were also assessed. Our studies revealed that Coll-SS hydrogels
      improved with 10% HA and 5% CS displayed the best biological performances in
      terms of cell viability, proliferation, morphology, and distribution. Thus,
      further work will address a novel 3D system including both HA 10% and CS 5%
      glycoproteins, which will probably be exposed to prochondrogenic conditions in
      order to assess its potential use in CTE applications. 

PMID- 24308002
TI  - Development of an immunochromatographic test strip for detection of cholera
      toxin.
AB  - Because cholera toxin (CT) is responsible for most of the symptoms induced by
      Vibrio cholerae infection, detection of CT is critical for diagnosis of the
      disease. In this study, we constructed an immunochromatographic test strip for
      detection of CT (CT-IC) with polyclonal antibodies developed against purified
      recombinant whole CT protein. The detection limit of the CT-IC was 10 ng/mL of
      purified recombinant CT, and it could detect the CT in culture supernatant of all
      15 toxigenic V. cholerae isolates examined, whereas no false-positive signal was
      detected in all 5 nontoxigenic V. cholerae isolates examined. The specificity of
      the CT-IC was examined with recombinant heat-labile toxin (LT), which shares high
      homology with CT, and it was revealed that the minimum detection limit for LT was
      100 times higher than that for CT. In addition, lt gene-positive enterotoxigenic
      Escherichia coli (ETEC) was examined by CT-IC. The false-positive signals were
      observed in 3 out of 12 ETEC isolates, but these signals were considerably faint.
      The CT-IC did not develop false-positive signals with all 7 V. parahaemolyticus
      isolates. These results showed the high specificity of CT-IC and the feasible use
      of it for the detection and surveillance of toxigenic V. cholerae.

PMID- 24308003
TI  - Rapid identification of aldose reductase inhibitory compounds from Perilla
      frutescens.
AB  - The ethyl acetate (EtOAc) soluble fraction of methanol extracts of Perilla
      frutescens (P. frutescens) inhibits aldose reductase (AR), the key enzyme in the
      polyol pathway. Our investigation of inhibitory compounds from the EtOAc soluble
      fraction of P. frutescens was followed by identification of the inhibitory
      compounds by a combination of HPLC microfractionation and a 96-well enzyme assay.
      This allowed the biological activities to be efficiently matched with selected
      HPLC peaks. Structural analyses of the active compounds were performed by LC
      MS(n). The main AR inhibiting compounds were tentatively identified as
      chlorogenic acid and rosmarinic acid by LC-MS(n). A two-step high speed counter
      current chromatography (HSCCC) isolation method was developed with a solvent
      system of n-hexane-ethyl acetate-methanol-water at 1.5:5:1:5, v/v and 3:7:5:5,
      v/v. The chemical structures of the isolated compounds were determined by (1)H-
      and (13)C-nuclear magnetic resonance spectrometry (NMR). The main compounds
      inhibiting AR in the EtOAc fraction of methanol extracts of P. frutescens were
      identified as chlorogenic acid (2) (IC50 = 3.16 MU M), rosmarinic acid (4) (IC50
      = 2.77 MU M), luteolin (5) (IC50 = 6.34 MU M), and methyl rosmarinic acid (6)
      (IC50 = 4.03 MU M).

PMID- 24308004
TI  - Improved scFv anti-HIV-1 p17 binding affinity guided from the theoretical
      calculation of pairwise decomposition energies and computational alanine
      scanning.
AB  - Computational approaches have been used to evaluate and define important residues
      for protein-protein interactions, especially antigen-antibody complexes. In our
      previous study, pairwise decomposition of residue interaction energies of single
      chain Fv with HIV-1 p17 epitope variants has indicated the key specific residues
      in the complementary determining regions (CDRs) of scFv anti-p17. In this present
      investigation in order to determine whether a specific side chain group of
      residue in CDRs plays an important role in bioactivity, computational alanine
      scanning has been applied. Molecular dynamics simulations were done with several
      complexes of original scFv anti-p17 and scFv anti-p17mutants with HIV-1 p17
      epitope variants with a production run up to 10 ns. With the combination of
      pairwise decomposition residue interaction and alanine scanning calculations, the
      point mutation has been initially selected at the position MET100 to improve the
      residue binding affinity. The calculated docking interaction energy between a
      single mutation from methionine to either arginine or glycine has shown the
      improved binding affinity, contributed from the electrostatic interaction with
      the negative favorably interaction energy, compared to the wild type. Theoretical
      calculations agreed well with the results from the peptide ELISA results.

PMID- 24308005
TI  - Helminth protein vaccine induced follicular T helper cell for enhancement of
      humoral immunity against Schistosoma japonicum.
AB  - Protein vaccines combined with adjuvants have been widely used to induce immune
      responses, especially the humoral immune response, against molecular targets
      including parasites. Follicular T helper (Tfh) cells are the specialized
      providers of B-cell help, however, the induction of Tfh cells in protein
      vaccination has been rarely studied. Here, we report that the Schistosoma
      japonicum recombinant protein (SjGST-32) combined with tacrolimus (FK506)
      augmented the induction of Tfh cells, which expressed the canonical markers
      CXCR5, BCL6, and IL-21, and enhanced the humoral immune responses in BALB/c mice.
      Furthermore, the expression of IL-21R on germinal center (GC) B cells and memory
      B cells increased in immunized mice, which indicated that IL-21 from the induced
      Tfh cells interacted with IL-21R for activation of B cells and maintenance of
      long-lived humoral immunity. Our results suggest that helminth protein vaccine
      combined with FK506 induces Tfh cell for stimulating humoral immune responses and
      inducing long-lived humoral immunity. 

PMID- 24308007
TI  - High expression and purification of amino-terminal fragment of human amyloid
      precursor protein in Pichia pastoris and partial analysis of its properties.
AB  - The cleaved amino-terminal fragment of human amyloid precursor protein (N-APP)
      binds death receptor 6 (DR6) and triggers a caspase-dependent self-destruction
      process, which was suggested to contribute to Alzheimer's disease. To investigate
      the N-APP-DR6-induced degeneration pathway at the molecular level, obtaining
      abundant and purified N-APP is fundamental and critical. The recombinant N-APP
      has been produced in mammalian expression system. However, the cost and yield
      disadvantages of mammalian expression system make it less ideal for protein mass
      production. Here, we successfully expressed and purified recombinant N-terminal
      18-285 amino acid residues of human amyloid precursor protein from the
      methylotrophic yeast Pichia pastoris with a high yield of 50 mg/L. Flow cytometry
      indicated the purified N-APP-induced obvious apoptosis of human neuroblastoma
      SHEP cells.

PMID- 24308008
TI  - Functional status in behavioral variant frontotemporal dementia: a systematic
      review.
AB  - The aim was to conduct a systematic review of studies that described the
      functional profile of patients with behavioral variant frontotemporal dementia
      (bvFTD), published between 2000 and 2013. The bibliographic search was conducted
      using the terms "frontotemporal dementia" and "frontotemporal lobar degeneration"
      in combination with "independence," "functionality," "basic activities of daily
      living," "disability," and scales that measure functional performance:
      "Disability Assessment for Dementia-DAD," "Functional Activities Questionnaire
      (FAQ)," "Direct Assessment of Functional Status (DAFS)." To be included in the
      review, the study had to mention the characterization of the functional status of
      patients with bvFTD in the objectives of the study, using a previously validated
      instrument of functional assessment. Fourteen studies met this criterion. The
      reviewed studies suggested that individuals with bvFTD have greater functional
      impairment when compared to those with other subtypes of frontotemporal lobar
      degeneration or Alzheimer's disease. The studies documented a significant
      association between cognitive impairment and measures of functionality in these
      patients. The cognitive profile of patients may predict faster functional
      decline. 

PMID- 24308006
TI  - Propionibacterium acnes: an underestimated pathogen in implant-associated
      infections.
AB  - The role of Propionibacterium acnes in acne and in a wide range of inflammatory
      diseases is well established. However, P. acnes is also responsible for
      infections involving implants. Prolonged aerobic and anaerobic agar cultures for
      14 days and broth cultures increase the detection rate. In this paper, we review
      the pathogenic role of P. acnes in implant-associated infections such as
      prosthetic joints, cardiac devices, breast implants, intraocular lenses,
      neurosurgical devices, and spine implants. The management of severe infections
      caused by P. acnes involves a combination of antimicrobial and surgical treatment
      (often removal of the device). Intravenous penicillin G and ceftriaxone are the
      first choice for serious infections, with vancomycin and daptomycin as
      alternatives, and amoxicillin, rifampicin, clindamycin, tetracycline, and
      levofloxacin for oral treatment. Sonication of explanted prosthetic material
      improves the diagnosis of implant-associated infections. Molecular methods may
      further increase the sensitivity of P. acnes detection. Coating of implants with
      antimicrobial substances could avoid or limit colonization of the surface and
      thereby reduce the risk of biofilm formation during severe infections. Our
      understanding of the role of P. acnes in human diseases will likely continue to
      increase as new associations and pathogenic mechanisms are discovered. 

PMID- 24308009
TI  - Abnormal nerve conduction study findings indicating the existence of peripheral
      neuropathy in multiple sclerosis and neuromyelitis optica.
AB  - OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) has been
      reported in patients with multiple sclerosis (MS). However, there have been
      limited reports of peripheral neuropathy as a complication of neuromyelitis
      optica (NMO). In this paper, we showed the characteristics and differences
      between peripheral neuropathy as a complication of MS and NMO. METHOD: We
      analyzed a series of 58 MS and 28 NMO patients and evaluated nerve conduction
      studies (NCS) in 21 MS and 5 NMO patients. RESULTS: Six of the 58 MS and 3 of the
      28 NMO patients revealed abnormal NCS findings. Three (5.2%) of the 58 MS
      patients fulfilled the criteria for CIDP. One (3.6%) of the 28 NMO patients
      showed peripheral neuropathy at the same time of NMO relapse, although CIDP was
      not seen in NMO. The other 5 (3 MS and 2 NMO) patients were complicated with
      neuropathy caused by concomitant diabetes mellitus and Sjogren's syndrome.
      CONCLUSION: Frequency of abnormal NCS findings might exhibit no significant
      difference between MS and NMO, although the cause and pathophysiology of
      peripheral neuropathy were different in MS and in NMO. There might be a group of
      NMO who were affected simultaneously in the central and peripheral nervous
      tissues.

PMID- 24308011
TI  - Proximal-type Epithelioid Sarcoma of the Head and Neck (HN): A Study with
      Immunohistochemical and Molecular Analysis of SMARCB1.
AB  - Proximal-type epithelioid sarcoma is an aggressive variant of epithelioid sarcoma
      most often occurring in soft tissues of the proximal limbs, characterized by
      polygonal cells, marked nuclear atypia, and varied rhabdoid features. Malignant
      rhabdoid tumor is an aggressive, well characterized entity typically with
      rhabdoid morphology and involving the kidney of pediatric patients. Rarely,
      tumors with morphologic and biologic features identical to those in kidney occur
      in extra-renal sites and are regarded as an extrarenal presentation of the same
      entity in kidney, named malignant extra-renal rhabdoid tumor. Morphologic and
      immunophenotypical similarities between proximal-type epithelioid sarcoma and
      malignant rhabdoid tumor pose a diagnostic challenge and may suggest a
      relationship between the two. Both tumors are characterized by loss of SMARCB1
      (INI1/BAF47/SNF5) expression; however, the molecular events involved differ. Here
      we describe the immunohistochemical and molecular analysis of three head and neck
      tumors with morphologic features shared by proximal-type epithelioid sarcoma and
      malignant rhabdoid tumor. All tumors showed loss of SMARCB1expression. Direct
      sequencing of the promoter and nine coding exons of SMARCB1, multiplex ligation
      dependent probe amplification, and whole genome single nucleotide polymorphism
      array were performed on the two adult cases and showed only a heterozygous
      deletion of chromosome 22 in a minority of cells in one of the cases. Though
      rare, proximal-type epithelioid sarcoma could occur in the head and neck and
      should be differentiated from other epithelioid tumors by the loss of SMARCB1
      expression. The lack of detectable genetic alteration in the SMARCB1 locus in
      head and neck proximal-type epithelioid sarcoma warrants further investigation
      into the molecular mechanism underlying loss of SMARCB1 expression.

PMID- 24308010
TI  - Performance of glutamate dehydrogenase and triose phosphate isomerase genes in
      the analysis of genotypic variability of isolates of Giardia duodenalis from
      livestocks.
AB  - Giardia duodenalis is a small intestinal protozoan parasite of several
      terrestrial vertebrates. This work aims to assess the genotypic variability of
      Giardia duodenalis isolates from cattle, sheep and pigs in the Southeast of
      Brazil, by comparing the standard characterization between glutamate
      dehydrogenase (gdh) and triose phosphate isomerase (tpi) primers. Fecal samples
      from the three groups of animals were analyzed using the zinc sulphate
      centrifugal flotation technique. Out of 59 positive samples, 30 were from cattle,
      26 from sheep and 3 from pigs. Cyst pellets were stored and submitted to PCR and
      nested-PCR reactions with gdh and tpi primers. Fragment amplification of gdh and
      tpi genes was observed in 25 (42.4%) and 36 (61.0%) samples, respectively.
      Regarding the sequencing, 24 sequences were obtained with gdh and 20 with tpi.
      For both genes, there was a prevalence of E specific species assemblage, although
      some isolates have been identified as A and B, by the tpi sequencing. This has
      also shown a larger number of heterogeneous sequences, which have been attribute
      to mixed infections between assemblages B and E. The largest variability of inter
      assemblage associated to the frequency of heterogeneity provided by tpi
      sequencing reinforces the polymorphic nature of this gene and makes it an
      excellent target for studies on molecular epidemiology. 

PMID- 24308012
TI  - Expression of VHL Causes Three-Dimensional Morphological Changes in Renal Cells
      Indicative of Proximal Tubule Differentiation.
AB  - Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are responsible
      for the VHL hereditary cancer syndrome, and are associated with the majority of
      clear cell renal cell carcinomas. In this study, scanning electron microscopy of
      VHL-negative renal carcinoma cells was utilized to examine the effects of VHL re
      expression on the morphology of these cells. Significant differences were
      observed between the morphology of VHL-negative control cells and those with
      reintroduced VHL, with VHL expression mediating an apical surface that mounded
      upward, as opposed to the flat surfaces seen with VHL-negative cells. In long
      term cultures, rounded VHL-expressing cells grew in clusters on top the
      monolayer, and microvilli were observed on the apical face of these cells, in a
      manner suggestive of proximal tubule differentiation. In contrast, VHL-negative
      cells remained flat and did not develop microvilli in long-term cultures. Since
      VHL is a key member of an ubiquitin E3 ligase complex whose best known target is
      hypoxia-inducible factor alpha (HIF-alpha), we looked at the effects of HIF-alpha
      expression on cell morphology. Knockdown of HIF-2alpha in cells that only express
      this isoform had no effect on the morphology of the cells. These results indicate
      that VHL expression directs three dimensional morphological changes in renal
      cells indicative of differentiation, and while dysregulation of HIF-alpha may be
      necessary for tumorigenesis following VHL loss, it is not the major determinant
      of these VHL-mediated morphological changes.

PMID- 24308013
TI  - Direct and Mediated Effects of a Social-Emotional and Character Development
      Program on Adolescent Substance Use.
AB  - Mitigating and preventing substance use among adolescents requires approaches
      that address the multitude of factors that influence this behavior. Such
      approaches must be tested, not only for evidence of empirical effectiveness, but
      also to determine the mechanisms by which they are successful. The aims of the
      present study were twofold: 1) To determine the effectiveness of a school-based
      social-emotional and character development (SECD) program, Positive Action (PA),
      in reducing substance use (SU) among a sample of U.S. youth living in a low
      income, urban environment, and 2) to test one mechanism by which the program
      achieves its success. We used longitudinal mediation analysis to test the
      hypotheses that: 1) students attending PA intervention schools engage in
      significantly less SU than students attending control schools, 2) students
      attending PA intervention schools show significantly better change in SECD than
      students attending control schools, and 3) the effect of the PA intervention on
      SU is mediated by the change in SECD. Analyses revealed program effects on both
      SECD and SU, a relationship between SECD and SU, and the effects of PA on SU were
      completely mediated by changes in SECD. Future research directions and
      implications for school-based social-emotional and character development efforts
      and substance use prevention are addressed.

PMID- 24308014
TI  - A Parallel Point Matching Algorithm for Landmark Based Image Registration Using
      Multicore Platform.
AB  - Point matching is crucial for many computer vision applications. Establishing the
      correspondence between a large number of data points is a computationally
      intensive process. Some point matching related applications, such as medical
      image registration, require real time or near real time performance if applied to
      critical clinical applications like image assisted surgery. In this paper, we
      report a new multicore platform based parallel algorithm for fast point matching
      in the context of landmark based medical image registration. We introduced a non
      regular data partition algorithm which utilizes the K-means clustering algorithm
      to group the landmarks based on the number of available processing cores, which
      optimize the memory usage and data transfer. We have tested our method using the
      IBM Cell Broadband Engine (Cell/B.E.) platform. The results demonstrated a
      significant speed up over its sequential implementation. The proposed data
      partition and parallelization algorithm, though tested only on one multicore
      platform, is generic by its design. Therefore the parallel algorithm can be
      extended to other computing platforms, as well as other point matching related
      applications.

PMID- 24308015
TI  - Novel amikacin inhaled formulation for the treatment of lower respiratory tract
      infections.
AB  - Lower respiratory tract infections are usually treated with systemic antibiotics,
      but sometimes in certain conditions inhaled antibiotics may also be used. In
      cystic fibrosis (CF) for example, inhaled tobramycin is used to treat chronic
      airways infection due to Pseudomonas aeruginosa, and in other conditions such as
      ventilator-associated pneumonia, inhaled colistin is used as add-on therapy to
      reduce the risk of side effects of prolonged systemic exposure. Other inhaled
      antibiotics are currently under development, and inhaled amikacin is one such
      example. The two formulations of inhaled amikacin currently under clinical
      development may have two different therapeutic trajectories: the nebulized
      liposomal formulation is the first once-daily aminoglycoside for CF patients,
      whereas the free nebulized amikacin may be used in addition to systemic therapy
      in ventilator-associated pneumonia patients exploiting reduced systemic exposure
      to amikacin as a therapeutic advantage, especially in patients with renal
      impairment. 

PMID- 24308016
TI  - Denosumab: a new treatment option for giant cell tumor of bone.
AB  - Giant cell tumor of bone (GCTB) is an osteolytic, usually benign neoplasm
      characterized by infiltration with osteoclast-like giant cells, and the
      osteoclast differentiation factor receptor activator of nuclear factor kappa-B
      ligand (RANKL) is heavily involved in its pathogenesis. Denosumab belongs to a
      new class of drugs that inhibit RANKL. Prior to denosumab, multimodality
      treatment in refractory, recurrent and metastatic GCTB has shown variable
      results. Recent phase II data have demonstrated denosumab's activity with regard
      to disease and symptom control, without significant adverse effects. On the basis
      of this data, the FDA approved denosumab for the treatment of patients whose GCTB
      is unresectable, or when surgery is likely to result in severe morbidity. Ongoing
      questions remain, including the optimal scheduling, patient selection, use in the
      adjuvant setting and long-term toxicity concerns. 

PMID- 24308017
TI  - Trastuzumab emtansine for the treatment of HER2-positive metastatic breast
      cancer.
AB  - Trastuzumab emtansine is an antibody-drug conjugate comprised of the receptor
      tyrosine-protein kinase erbB-2 (HER2) antibody trastuzumab, and a derivative of
      the cytostatic agent maytansinoid DM1, covalently linked by a thiol linker. The
      drug was developed in an attempt to overcome trastuzumab resistance in patients
      with HER2-positive breast carcinoma, but it is also of potential use in other
      HER2-positive cancers. The preclinical antitumor activity of trastuzumab
      emtansine was established in HER2-positive breast cancer cell lines and murine
      xenograft models. Preclinically, trastuzumab emtansine was efficacious in HER2
      positive cells that were resistant to trastuzumab or lapatinib. Clinically, the
      drug is well tolerated in most patients, with a predictable pharmacokinetic
      profile and minimal systemic exposure to free cytotoxic DM1. Unlike with
      trastuzumab, cardiac toxicity has not been seen in patients receiving trastuzumab
      emtansine and less adverse events have been reported than with other chemotherapy
      regimens. Results from a number of phase II studies and early results from a
      phase III investigation (EMILIA) demonstrated response rates of 25-35% in
      patients with breast cancer who had previously received trastuzumab. Several
      phase II and III studies are under way investigating trastuzumab emtansine in
      combination with other regimens in patients with HER2-positive cancers. 

PMID- 24308018
TI  - A report from the American College of Rheumatology 2013 Meeting (October 26-30,
      2013 - San Diego, California, USA).
AB  - The American College of Rheumatology annual meeting opened in San Diego,
      California, with a poster session in which prominent clinical and preclinical
      research into experimental and putative novel therapies for rheumatoid arthritis
      and other inflammatory conditions were discussed. The meeting continued through 2
      more days of poster presentations and 4 days of very active oral sessions, in
      which information was discussed on therapeutics and candidate drugs for managing
      rheumatological diseases ranging from rheumatoid arthritis, osteoarthritis and
      systemic lupus erythematosus to many other conditions frequently seen in the
      rheumatology ward. The following report summarizes a selection of oral and poster
      presentations that reflect the state of the art of current rheumatology
      pharmacotherapy and what is arising as novel investigational therapy. 

PMID- 24308019
TI  - A report from Biopharm America 2013 - sixth Annual International Partnering
      Conference (September 16-19, 2013 - Boston, Massachusetts, USA).
AB  - The sixth Annual International Partnering Conference, Biopharm America 2013, took
      full advantage of its setting in Boston, Massachusetts, home of perhaps the
      greatest concentration of academic institutions in the U.S., if not the world.
      With a keynote address from a systems biologist from Harvard University, a
      networking reception at the Boston Museum of Science and a spirited 'Academic
      Innovators Showcase', the EBD Group's gathering paid homage to the links between
      a steady flow of new scientific ideas and a healthy biopharmaceutical pipeline. 

PMID- 24308020
TI  - A report from CPhI Worldwide 2013, Fifth Annual Pre-Connect Conference (October
      22-24, 2013 - Frankfurt, Germany).
AB  - A day before the start of the 2013 Conference on Pharmaceutical Ingredients
      (CPhI) Worldwide, the world's leading pharmaceutical networking event, a number
      of attendees gathered for the Fifth Annual Pre-Connect Conference to discuss
      trends in business development, manufacturing and regulatory arenas. Of the six
      modules presented at the meeting, one was dedicated to the sourcing environment
      in emerging markets, with special attention paid to developments in India and
      China. Other modules evaluated the current trends in the creation of generics and
      supergenerics in emerging markets. Additionally, there were updates on issues
      surrounding the regulatory and development hurdles that biosimilars and
      biobetters are facing today. Common themes for both discussions include
      appropriate pricing and erosion demographics for generics and biosimilars,
      licensing scenarios, commercialization strategies, and how to stay competitive
      and find novel innovations within new delivery systems, improved formulations and
      modifications to create better quality active pharmaceutical ingredients. 

PMID- 24308021
TI  - Infant pain regulation as an early indicator of childhood temperament.
AB  - BACKGROUND: There is considerable variability in infants' responses to painful
      stimuli, including facial and vocal expressions. This variability in pain-related
      distress response may be an indicator of temperament styles in childhood.
      OBJECTIVE: To examine the relationships among immunization pain outcomes (pain
      reactivity, pain regulation and parent ratings of infant pain) over the first
      year of life and parent report of early temperament. METHODS: A subset of parent
      infant dyads in an ongoing Canadian longitudinal cohort was studied. Infant pain
      behaviours were coded using the Modified Behavior Pain Scale. Parental judgments
      of infant pain were recorded using the Numeric Rating Scale. Infant temperament
      was measured using the Infant Behaviour Questionnaire-Revised. Correlational
      analyses and multiple regressions were conducted. RESULTS: Multiple regressions
      revealed that the 12-month regulatory pain scores predicted parent ratings of the
      Negative Affectivity temperament dimension at 14 months of age. Parent ratings of
      infant pain at 12 months of age predicted parent ratings of the
      Orienting/Affiliation temperament dimension, with sex differences observed in
      this substrate. CONCLUSION: Pain-related distress regulation at one year of age
      appears to be a novel indicator of parent report of temperament ratings. Pain
      outcomes in the first six months of life were not related to parent temperament
      ratings.

PMID- 24308022
TI  - Motor function predicts parent-reported musculoskeletal pain in children with
      cerebral palsy.
AB  - BACKGROUND: The relationship between pain and motor function is not well
      understood, especially for children and adolescents with communication and motor
      impairments associated with cerebral palsy (CP). OBJECTIVES: To determine whether
      a predictive relationship between motor function and musculoskeletal pain exists
      in children with CP. METHODS: Following informed consent, caregivers of 34
      pediatric patients with CP (mean [+/- SD] age 9.37+/-4.49 years; 80.0% male)
      completed pain- and function-related measures. Parents completed the Dalhousie
      Pain Interview and the Brief Pain Inventory based on a one-week recall to
      determine whether pain had been experienced in the past week, its general
      description, possible cause, duration, frequency, intensity and interference with
      daily function. The Gross Motor Function Classification System (GMFCS) was used
      to classify the motor involvement of the child based on their functional ability
      and their need for assistive devices for mobility. RESULTS: GMFCS level
      significantly predicted parent-reported musculoskeletal pain frequency (P<0.02),
      duration (P=0.05) and intensity (P<0.01). Duration of pain was significantly
      related to interference with activities of daily living (P<0.05). CONCLUSIONS:
      Children with CP with greater motor involvement, as indexed by GMFCS level, may
      be at risk for increased pain (intensity, frequency and duration) that interfers
      with activities of daily living. The clinical index of suspicion should be raised
      accordingly when evaluating children with developmental disability who cannot
      self-report reliably.

PMID- 24308025
TI  - Reduction of pain thresholds in fibromyalgia after very low-intensity magnetic
      stimulation: a double-blinded, randomized placebo-controlled clinical trial.
AB  - BACKGROUND: Exposure to electromagnetic fields has been reported to have
      analgesic and antinociceptive effects in several organisms. OBJECTIVE: To test
      the effect of very low-intensity transcranial magnetic stimulation on symptoms
      associated with fibromyalgia syndrome. METHODS: A double-blinded, placebo
      controlled clinical trial was performed in the Sagrado Corazon Hospital, Seville,
      Spain. Female fibromyalgia patients (22 to 50 years of age) were randomly
      assigned to either a stimulation group or a sham group. The stimulation group
      (n=28) was stimulated using 8 Hz pulsed magnetic fields of very low intensity,
      while the sham group (n=26) underwent the same protocol without stimulation.
      Pressure pain thresholds before and after stimulation were determined using an
      algometer during the eight consecutive weekly sessions of the trial. In addition,
      blood serotonin levels were measured and patients completed questionnaires to
      monitor symptom evolution. RESULTS: A repeated-measures ANOVA indicated
      statistically significant improvement in the stimulation group compared with the
      control group with respect to somatosensory pain thresholds, ability to perform
      daily activities, perceived chronic pain and sleep quality. While improvement in
      pain thresholds was apparent after the first stimulation session, improvement in
      the other three measures occurred after the sixth week. No significant between
      group differences were observed in scores of depression, fatigue, severity of
      headaches or serotonin levels. No adverse side effects were reported in any of
      the patients. CONCLUSIONS: Very low-intensity magnetic stimulation may represent
      a safe and effective treatment for chronic pain and other symptoms associated
      with fibromyalgia.

PMID- 24308026
TI  - Validation and evaluation of two observational pain assessment tools in a trauma
      and neurosurgical intensive care unit.
AB  - BACKGROUND: Studies have demonstrated that patients in the intensive care unit
      experience high levels of pain. While many of these patients are nonverbal at
      some point during their stay, there are few valid tools available to assess pain
      in this group. OBJECTIVES: To evaluate the validity and clinical utility of two
      pain assessment tools, the revised Adult Non-Verbal Pain Scale (NVPS-R) and the
      Critical Care Pain Observation Tool (CPOT), in a trauma and neurosurgical patient
      population. METHODS: Patients were assessed using the NVPS-R and CPOT by trained
      intensive care unit nurses (n=23) and research assistants before, during and
      after two procedures: turning of the patient (nociceptive procedure) and
      noninvasive blood pressure cuff inflation (non-nociceptive procedure).
      Communicative patients were also asked to report their level of pain during each
      assessment. RESULTS: A total of 66 patients (34 communicative, 32
      noncommunicative) were included in the study. CPOT and NVPS-R scores increased
      significantly when participants were exposed to turning, but not during
      noninvasive blood pressure measurement (repeated measures ANOVA: CPOT, F=5.81,
      P=0.019; NVPS-R, F=5.32, P=0.025) supporting discriminant validity. CPOT and NVPS
      R scores were significantly higher during the turning procedure for patients who
      had indicated that they were in pain versus those who were not, indicating
      criterion validity. Inter-rater reliability was generally higher for the CPOT
      than NVPS-R. Nurses rated the feasibility of the two tools as comparable but
      provided higher ratings of acceptability for the CPOT. CONCLUSIONS: While the
      present study supports the use of the CPOT and the NVPS-R with critically ill
      trauma and neurosurgical patients, further research should explore the role of
      vital signs in pain.

PMID- 24308027
TI  - Living with difference: exploring the social self of adolescents with chronic
      pain.
AB  - BACKGROUND: Chronic pain negatively affects an adolescent's life; however, little
      is known about the social impact of chronic pain for adolescents. More is known
      about the general peer relationships of adolescents with chronic pain than their
      close friendships. Close friendships begin to take on more importance during
      adolescence as these relationships facilitate the development of an adolescent's
      sense of personal identity and increasing independence from family influences.
      Thus, chronic pain may create friendship challenges for adolescents beyond those
      typically experienced during this developmental trajectory, which may negatively
      impact their abilities to secure social support. OBJECTIVES: To better understand
      the challenges adolescents with chronic pain face with regard to their
      friendships. METHODS: An interpretative phenomenological study using individual
      interviews was conducted. RESULTS: Two themes emerged. 'Rethinking the self with
      pain' describes the intrusive nature of chronic pain, challenging the
      participants to rethink the way they view themselves and their place within their
      social network. 'Rethinking friendships' describes the interpretation of their
      friends' reactions to their chronic pain condition, which led to these
      adolescents spending more time by themselves, and feeling misunderstood and
      unsupported. CONCLUSIONS: The impact of chronic pain on the adolescent as an
      individual as well as the responses of close friends and others within their
      social network resulted in the development of new friendship needs. However, the
      adolescents were not always able to secure these new friendship needs. Their
      experiences suggest factors within friendships that may be ameliorated by
      interventions, thus maintaining and strengthening their close friendships.

PMID- 24308028
TI  - Establishing intra- and inter-rater agreement of the Face, Legs, Activity, Cry,
      Consolability scale for evaluating pain in toddlers during immunization.
AB  - BACKGROUND: The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a five
      item tool that was developed to assess postoperative pain in young children. The
      tool is frequently used as an outcome measure in studies investigating acute
      procedural pain in young children; however, there are limited published
      psychometric data in this context. OBJECTIVE: To establish inter-rater and
      intrarater agreement of the FLACC scale in toddlers during immunization. METHODS:
      Participants comprised a convenience sample of toddlers recruited from an
      immunization drop-in service, who were part of a larger pilot randomized
      controlled trial. Toddlers were video- and audiotaped during immunization
      procedures. The first rater scored each video twice in random order over a period
      of three weeks (intrarater agreement), while the second rater scored each video
      once and was blinded to the first rater's scores (inter-rater agreement). The
      FLACC scale was scored at four timepoints throughout the procedure. Intraclass
      correlation coefficients were used to assess agreement of the FLACC scale.
      RESULTS: Thirty toddlers between 12 and 18 months of age were recruited, and
      video data were available for 29. Intrarater agreement coefficients were 0.88 at
      baseline, 0.97 at insertion of first needle, and 0.80 and 0.81 at 15 s and 30 s
      following the final injection, respectively. Inter-rater coefficients were 0.40
      at baseline, 0.95 at insertion of first needle, and 0.81 and 0.78 at 15 s and 30
      s following the final injection, respectively. CONCLUSIONS: The FLACC scale has
      sufficient agreement in assessing pain in toddlers during immunizations,
      especially during the most painful periods of the procedure.

PMID- 24308030
TI  - Effect of substrate choice and tissue type on tissue preparation for spectral
      histopathology by Raman microspectroscopy.
AB  - Raman spectroscopy is a non-destructive, non-invasive, rapid and economical
      technique which has the potential to be an excellent method for the diagnosis of
      cancer and understanding disease progression through retrospective studies of
      archived tissue samples. Historically, biobanks are generally comprised of
      formalin fixed paraffin preserved tissue and as a result these specimens are
      often used in spectroscopic research. Tissue in this state has to be dewaxed
      prior to Raman analysis to reduce paraffin contributions in the spectra. However,
      although the procedures are derived from histopathological clinical practice, the
      efficacy of the dewaxing procedures that are currently employed is questionable.
      Ineffective removal of paraffin results in corruption of the spectra and previous
      experiments have shown that the efficacy can depend on the dewaxing medium and
      processing time. The aim of this study was to investigate the influence of
      commonly used spectroscopic substrates (CaF2, Spectrosil quartz and low-E slides)
      and the influence of different histological tissue types (normal, cancerous and
      metastatic) on tissue preparation and to assess their use for spectral
      histopathology. Results show that CaF2 followed by Spectrosil contribute the
      least to the spectral background. However, both substrates retain paraffin after
      dewaxing. Low-E substrates, which exhibit the most intense spectral background,
      do not retain wax and resulting spectra are not affected by paraffin peaks. We
      also show a disparity in paraffin retention depending upon the histological
      identity of the tissue with abnormal tissue retaining more paraffin than normal. 

PMID- 24308029
TI  - A systematic review of the effectiveness of knowledge translation interventions
      for chronic noncancer pain management.
AB  - BACKGROUND: Reliable evidence detailing effective treatments and management
      practices for chronic noncancer pain exists. However, little is known about which
      knowledge translation (KT) interventions lead to the uptake of this evidence in
      practice. OBJECTIVES: To conduct a systematic review of the effectiveness of KT
      interventions for chronic noncancer pain management. METHODS: Comprehensive
      searches of electronic databases, the gray literature and manual searches of
      journals were undertaken. Randomized controlled trials, controlled clinical
      trials and controlled before-and-after studies of KT interventions were included.
      Data regarding interventions and primary outcomes were categorized using a
      standard taxonomy; a risk-of-bias approach was adopted for study quality. A
      narrative synthesis of study results was conducted. RESULTS: More than 8500
      titles and abstracts were screened, with 230 full-text articles reviewed for
      eligibility. Nineteen studies were included, of which only a small proportion
      were judged to be at low risk of bias. Interactive KT education for health care
      providers has a positive effect on patients' function, but its benefits for other
      health provider- and patient-related outcomes are inconsistent. Interactive
      education for patients leads to improvements in knowledge and function. Little
      research evidence supports the effectiveness of structural changes in health
      systems and quality improvement processes or coordination of care. CONCLUSIONS:
      KT interventions incorporating interactive education in chronic noncancer pain
      led to positive effects on patients' function and knowledge about pain. Future
      studies should provide implementation details and use consistent theoretical
      frameworks to better estimate the effectiveness of such interventions.

PMID- 24308031
TI  - Predicting detection limits of enzyme-linked immunosorbent assay (ELISA) and
      bioanalytical techniques in general.
AB  - The detection limit is one of the most important performance parameters for
      bioanalytical techniques. Here we present a generic method to estimate the
      detection limit of biomolecular assays based on a step-by-step analysis of the
      assay procedure. Enzyme-linked immunosorbent assay (ELISA) is used here as an
      example; however, much of the information presented in this article may be
      applied to other types of biomolecular assays and analytical techniques. A clear
      understanding of what affects the detection limit can help researchers to
      evaluate different bio-analytical techniques properly, and to design better
      strategies to optimize and achieve the best analytical performance. 

PMID- 24308034
TI  - [If you want to revoke an unconditional waiver, you must face high hurdles].

PMID- 24308032
TI  - The genomic landscape of oesophagogastric junctional adenocarcinoma.
AB  - The incidence of oesophagogastric junctional (OGJ) adenocarcinoma is rising
      rapidly in western countries, in contrast to the declining frequency of distal
      gastric carcinoma. Treatment options for adenocarcinomas involving the
      oesophagogastric junction are limited and the overall prognosis is extremely
      poor. To determine the genomic landscape of OGJ adenocarcinoma, exomes of eight
      tumours and matched germline DNA were subjected to massively parallel DNA
      sequencing. Microsatellite instability was observed in three tumours which
      coincided with an elevated number of somatic mutations. In total, 117 genes were
      identified that had predicted coding alterations in more than one tumour.
      Potentially actionable coding mutations were identified in 67 of these genes,
      including those in CR2, HGF , FGFR4, and ESRRB. Twenty-nine genes harbouring
      somatic coding mutations and copy number changes in the MSS OGJ dataset are also
      known to be altered with similar predicted functional consequence in other tumour
      types. Compared with the published mutational profile of gastric cancers, 49%
      (57/117) of recurrently mutated genes were unique to OGJ tumours. TP53, SYNE1,
      and ARID1A were amongst the most frequently mutated genes in a larger OGJ cohort.
      Our study provides an insight into the mutational landscape of OGJ
      adenocarcinomas and confirms that this is a highly mutated and heterogeneous
      disease. Furthermore, we have uncovered somatic mutations in therapeutically
      relevant genes which may represent candidate drug targets.

PMID- 24308033
TI  - The matricellular protein CCN3 regulates NOTCH1 signalling in chronic myeloid
      leukaemia.
AB  - Deregulated NOTCH1 has been reported in lymphoid leukaemia, although its role in
      chronic myeloid leukaemia (CML) is not well established. We previously reported
      BCR-ABL down-regulation of a novel haematopoietic regulator, CCN3, in CML; CCN3
      is a non-canonical NOTCH1 ligand. This study characterizes the NOTCH1-CCN3
      signalling axis in CML. In K562 cells, BCR-ABL silencing reduced full-length
      NOTCH1 (NOTCH1-FL) and inhibited the cleavage of NOTCH1 intracellular domain
      (NOTCH1-ICD), resulting in decreased expression of the NOTCH1 targets c-MYC and
      HES1. K562 cells stably overexpressing CCN3 (K562/CCN3) or treated with
      recombinant CCN3(rCCN3) showed a significant reduction in NOTCH1 signalling (>
      50% reduction in NOTCH1-ICD, p < 0.05).Gamma secretase inhibitor (GSI), which
      blocks NOTCH1 signalling, reduced K562/CCN3 colony formation but increased that
      of K562/control cells. GSI combined with either rCCN3 or imatinib reduced K562
      colony formation with enhanced reduction of NOTCH1 signalling observed with
      combination treatments. We demonstrate an oncogenic role for NOTCH1 in CML and
      suggest that BCR-ABL disruption of NOTCH1-CCN3 signalling contributes to the
      pathogenesis of CML.

PMID- 24308035
TI  - [If the MDK inquires].

PMID- 24308037
TI  - Reply to Mokany et al: Comprehensive measures of biodiversity are critical to
      investigations of ecosystem multifunctionality.

PMID- 24308036
TI  - Reply to Fontes-Villalba et al.: On a reluctance to conjecture about animal food
      consumption.

PMID- 24308038
TI  - Notes from the field: recurrent outbreak of Campylobacter Jejuni infections
      associated with a raw milk dairy-Pennsylvania, April-May 2013.

PMID- 24308039
TI  - Johnson & Johnson hunts for dengue fever drugs with academia.

PMID- 24308040
TI  - In the literature. Piperacillin-tazobactam and extended-spectrum beta-lactamase-
      producing Escherichia coli.

PMID- 24308041
TI  - Update on dental caries risk and caries lesion assessment.

PMID- 24308042
TI  - miRNAs targeting in glioma stem cell  maintenance.

PMID- 24308043
TI  - Special Issue: IX Nestle Nutrition Conference. Maternal obesity: reproduction,
      pregnancy, and offspring outcomes, November 8-9, 2012, Mexico City, Mexico.
      Foreword.

PMID- 24308044
TI  - Physical activity and working memory in healthy older adults: an ERP study.
AB  - This study examined the effects of physical activity on working memory in older
      adults using both behavioral and neuroelectric measures. Older adults were
      assigned to either a higher or lower physical activity group, and event-related
      potentials were recorded during assessments of a modified Sternberg task. The
      results indicated that older adults in the higher physical activity group
      exhibited shorter response times, independent of the working memory load.
      Enhanced P3 and N1 amplitudes and a decreased P3 latency were observed in the
      higher physical activity group. These findings suggested that physical activity
      facilitates working memory by allocating more attentional resources and
      increasing the efficiency of evaluating the stimulus during the retrieval phase
      as well as engaging more attentional resources for the early discriminative
      processes during the encoding phase of a working memory task.

PMID- 24308045
TI  - Education and imaging. Gastrointestinal: Symmetric lymphangitis of lower limbs
      originating from a perianal abscess.

PMID- 24308046
TI  - [Association between risk factors and (18)F-FDG-accumulation ].

PMID- 24308047
TI  - [Classification of traumatic intervertebral disc lesions].

PMID- 24308048
TI  - [Stiffness of the liver and HCC risk factor identification].

PMID- 24308050
TI  - [Concomitant PET-scan improves sensitivity].

PMID- 24308049
TI  - [Determination of prognostic factors].

PMID- 24308051
TI  - [Good image quality and reduced radiation dose for thoracic-CT].

PMID- 24308052
TI  - [Assessment of cognitive impairement in preterm infants with PVL].

PMID- 24308053
TI  - [Importance of steatosis for MR diagnosis].

PMID- 24308054
TI  - [MRT shows higher fracture rate].

PMID- 24308055
TI  - [Dose reduction could reduce the number of new cancer cases].

PMID- 24308056
TI  - [Intra-procedural cone-beam CT can predict response].

PMID- 24308057
TI  - [Effectiveness and safety of CTPA in elderly patients].

PMID- 24308058
TI  - [CT diagnosis of vascular closure].

PMID- 24308059
TI  - [Medical assistance: obtaining health care abroad].

PMID- 24308060
TI  - [A forgotten portrait of Markusovszky (Watercolor by Karoly Sterio)].

PMID- 24308061
TI  - [To the Editors: Author's reply regarding calcium metabolism in
      hyperparathyroidism].

PMID- 24308062
TI  - N-glycosylation affects the proper folding, enzymatic characteristics and
      production of a fungal beta-glucosidase.
AB  - Heterologous expression of beta-glucosidase is one of the approaches to enhance
      the efficiency of fungal cellulase preparations. It has been reported that N
      glycosylation affects the structure framework, function and stability of
      proteins. In this study, a beta-glucosidase from Aspergillus terreus (GenBank:
      XP_001216552, BglS) was heterologously expressed in Pichia pastoris and
      Trichoderma reesei. The four asparagine residues were all linked with high
      mannose-type oligosaccharides in P. pastoris, whereas only N224 carried high
      mannosetype glycan in T. reesei (the other three sites carried one N
      acetylglucosamine). The long N-glycan chains on PpBglS weakened its substrate
      affinity, activity and thermostability. The moderate post-translational and post
      secretory glycan modification in T. reesei makes it a suitable expression system
      for BglS. The N224 glycan played a critical role in BglS folding. The elucidation
      of the correlation between the different N-glycosylation patterns of BglS and
      their corresponding enzymatic characteristics is an important step towards
      improving the activity, thermostability and even production of heterologous beta
      glucosidase by glycan engineering.

PMID- 24308063
TI  - Disease spectrum of intraductal papillary mucinous neoplasm with an associated
      invasive carcinoma invasive IPMN versus pancreatic ductal adenocarcinoma
      associated IPMN.
AB  - OBJECTIVES: Current version of World Health Organization classification
      introduced the concept of ''intraductal papillary mucinous neoplasm(IPMN) with an
      associated invasive carcinoma.'' The authors investigated the clinicopathologic
      characteristics and prognosis of this disease category according to tumor
      morphology and percentage of invasive component. METHODS: Fifty-nine patients who
      underwent surgical resection of IPMN with an associated invasive carcinoma at
      Seoul National University Hospital were subgrouped according to the invasive
      component of less than 5% (minimally invasive [MI] intraductal papillary mucinous
      carcinoma [IPMC] [MI-IPMC]), 5%- 50% (invasive IPMC [IPMC-I]),and 50% or greater
      (pancreatic ductal adenocarcinoma [PDAC]-associated IPMN [PDAC-IPMN]). Prognosis
      was compared with 219 curatively resected conventional PDAC. RESULTS: Eleven MI
      IPMCs (18.6%), 24 IPMC-Is (40.7%), and 24PDAC-IPMNs (40.7%) were identified. With
      the transition from MIIPMC to IPMC-I and PDAC-IPMN, percentage of advanced T (P
      G0.001) or N stage (P = 0.001), expression of S100A4 (P = 0.004), p53(P = 0.028),
      and CD24 (P = 0.009) increased; and SMAD4 expression decreased (P G 0.001). The
      overall 5-year survival rates for MIIPMC,IPMC-I, and PDAC-IPMN were 80.8%, 59.0%,
      and 29.3%,respectively (P G 0.001). Pancreatic ductal adenocarcinoma-associated
      IPMN had poor prognosis compared with MI-IPMC (P = 0.011) or IPMC-I (P = 0.026)
      but had comparable prognosis with conventional PDAC (P = 0.138). CONCLUSIONS:
      Pancreatic ductal adenocarcinoma-associated IPMN has different
      clinicopathological characteristics compared with the IPMC-I.Intraductal
      papillary mucinous neoplasm with an associated invasive carcinoma is composed of
      a wide spectrum of disease.

PMID- 24308065
TI  - [Roger Charles Louis Guillemin].

PMID- 24308064
TI  - Migratory activity of CD105+ pancreatic cancer cells is strongly enhanced by
      pancreatic stellate cells.
AB  - OBJECTIVES: CD105 expression correlates with prognosis for several cancers.
      However, its significance in pancreatic cancer is unclear. METHODS: We analyzed
      CD105 expression in resected pancreatic cancer tissue and pancreatic cancer cell
      lines, compared the properties of CD105(+) and CD105(-) cells using quantitative
      RT-PCR and migration assays, and evaluated the relationship between CD105(+)
      cells and pancreatic stellate cells (PSCs). RESULTS: Immunohistochemistry showed
      that the frequency of CD105 expression was higher in pancreatic cancer than that
      in normal tissue(8% vs 0%, respectively). In flow cytometry, CD105 was expressed
      in pancreatic cancer cells, whereas weak CD105 expression was detected in normal
      pancreatic ductal epithelial cells. Quantitative RT-PCR showed that E-cadherin
      mRNA expression was suppressed and vimentin mRNA was overexpressed in CD105(+)
      cells (P < 0.05). Migration of CD105(+) cancer cells was strongly enhanced (more
      than that of CD105(+) cells) in coculture with PSCs (P < 0.05). CD105 expression
      did not correlate to clinicopathologic characteristics or the Kaplan-Meier
      survival analysis. CONCLUSIONS: Suppression of an epithelial marker and over
      expression of a mesenchymal marker suggest that epithelial-mesenchymal transition
      is induced in CD105(+) pancreatic cancer cells. CD105(+) pancreatic cancer cell
      migration is strongly enhanced by PSCs, suggesting that these cells play a role
      in the pancreatic cancer microenvironment.

PMID- 24308066
TI  - Mitomycin C versus 5-fluorouracil as an adjunctive  treatment for trabeculectomy:
      a meta-analysis of  randomized clinical trials.
AB  - Mitomycin C (MMC) and 5-fluorouracil (5-FU) are the most frequently utilized
      adjuvant therapies in trabeculectomy (TRAB), but there is no general consensus as
      to the direct comparative efficacy and safety of these two adjuvants. In this
      study, the authors conducted a meta-analysis to compare the efficacy and safety
      of augmenting TRAB with MMC or 5-FU. A systematic review with meta-analysis was
      conducted and five randomized controlled clinical trials comparing MMC versus 5
      FU as adjunctive therapies were identified, totaling 416 participants. A lower
      pooled mean IOP and higher complete and qualified success rates were observed in
      the MMC arm than in the 5-FU arm. Epithelial corneal defects were the unique
      complication reported more frequently with 5-FU compared to MMC treatment.
      Compared to TRAB with 5-FU, TRAB with MMC was associated with higher rates of
      complete and qualified surgical success and was not associated with increased
      incidences of postoperative complications.

PMID- 24308067
TI  - Nurse care managers, new programming aim to provide more outpatient care
      alternatives for ED patients on the margin.
AB  - The University of Michigan Health System is developing clinical programming and
      deploying specially trained care managers as part of an initiative aimed at
      eliminating unnecessary hospital admissions. The ED-based care managers will
      assess every patient who comes to the ED, but focus their time on developing
      outpatient care alternatives for patients on the margin when physicians are
      making admission vs. discharge decisions. The initial focus of the program will
      be on patients placed in observation, but developers plan to expand the program
      to include slightly more complicated patients as physicians become more
      comfortable with outpatient treatment alternatives. While the care managers are
      already being deployed in the ED, program developers are working with community
      partners to create a toolbox of outpatient care alternatives such as a visiting
      nurse program that can be activated by ED referral. Illustrating the potential
      for such a program, one new study showed that in a sampling of Medicare patients
      who underwent six common surgical procedures, nearly one in five of these
      patients had an ED visit within one month of their hospital stay, and more than
      half of these patients ended up back in the hospital.

PMID- 24308068
TI  - Lean-driven improvements eliminate waste, boost patient satisfaction in a matter
      of weeks.
AB  - To address declining volumes and suboptimal patient satisfaction in the ED,
      administrators at North Adams Regional Hospital used lean techniques to eliminate
      waste and streamline the triage process. A few months into the new approach,
      administrators say that average daily visits to the ED have increased from 42 to
      54, and patient satisfaction scores have jumped 25 points on Press Ganey surveys.
      Participants also report the approach has resulted in improved cooperation among
      ED staff and lower noise levels. Participants on a lean improvement team
      implemented a three-step triage process that connects patients with a provider
      quickly. The approach enables non-essential data gathering to take place later in
      the visit. The team also divided the ED into pods so that nurses can be assigned
      to three or four contiguous rooms. This approach eliminates unnecessary movement
      and makes it easier for physicians to find a patient's assigned nurse. The
      hospital is now leveraging the same improvement process to work on ED-to-hospital
      admissions and a process for handling unexpected patient surges.

PMID- 24308069
TI  - Prepare for enhanced scrutiny on infection control as regulators clamp down on
      unsafe practices related to health care-associated infections.
AB  - Government regulators are stepping up efforts to reduce harm from health care
      associated infections (HAI) in 2014. This is expected to include unannounced
      visits to hospitals by inspectors from the Centers for Medicare and Medicaid
      Services (CMS). Experts recommend that hospitals prepare for such visits by
      thoroughly reviewing the agency's revised worksheet for infection control, which
      reflects the latest guidelines and revisions. Further, administrators need to
      insure that staff are adhering to core best practices. The Centers for Disease
      Control (CDC) says there are 1.7 million HAI every year, resulting in 99,000 to
      100,000 deaths. The Department of Health and Human Services has devoted $1
      billion toward cracking down on the problem in 2014. As a result, hospitals
      should expect surveyors who are more knowledgeable about infection control than
      in the past. ED administrators need to pay particular attention to the CDC's
      Guide to Infection Prevention for Outpatient Settings.

PMID- 24308070
TI  - The Joint Commission aims for high-reliability health care, unveils framework to
      move hospitals toward zero harm.
AB  - To move hospitals toward what it terms high-reliability, The Joint Commission
      (TJC) is urging administrators to use a framework that it has developed to push
      their organizations through stages of maturity, ultimately creating environments
      in which there is zero patient harm. To get to this point, TJC leaders say
      hospitals will have to commit to transparency, promote and reward error
      reporting, and seize upon opportunities to improve. The Joint Commission has
      tested its high-reliability framework in seven hospitals, and it is now working
      on an assessment tool that will enable hospitals to measure their level of
      maturity across the framework's 14 components. The accrediting agency is urging
      hospitals to use a combination of Six Sigma, lean, and change management to make
      improvements that can be sustained. At some hospitals, entrenched practices of
      intimidation are dissuading staff from reporting unsafe practices and interfering
      with quality improvement efforts, according to TJC.

PMID- 24308071
TI  - New program set to intervene to prevent readmissions, repeat ED visits due to
      acute exacerbations of asthma.
AB  - Faculty at Indiana University School of Medicine are set to launch a community
      paramedicine program aimed at preventing repeat hospital and ED visits for acute
      exacerbations of asthma in children. Under the program, all children who are
      treated in the hospital or ED for asthma will receive home visits by specially
      trained paramedics within a few days of discharge. Paramedics will conduct a
      comprehensive assessment and make referrals as necessary for followup care.
      Nearly 30% of children who have been hospitalized for asthma require readmission
      to the hospital not long after discharge, and as many as 25% of children who have
      been treated in the ED for asthma will return to the ED within 30 days for
      another asthma-related visit. The one-time home visits will be comprehensive,
      enabling EMS providers to initiate stop-gap measures so that if a child is
      starting to get sick, paramedics can make sure the appropriate medicines are
      started and that acute care needs are met. Developers will monitor 30-day, 90
      day, and one-year readmission metrics among patients who have received home
      visits.They hope that resulting cost-savings will sustain the program beyond the
      initial period, which is being funded through a grant from the Department of
      Health and Human Services.

PMID- 24308076
TI  - The increase of cancer in New Zealand. 1913.

PMID- 24308077
TI  - Hugh Timothy Spencer.

PMID- 24308080
TI  - An identified neuron mediates the unconditioned stimulus in associative olfactory
      learning in honeybees.

PMID- 24308079
TI  - [Abstracts of Dermatological Days Paris 2013, the Annual Congress of
      Dermatological Research 2013. Paris, France. December 11-13, 2013].

PMID- 24308081
TI  - Gainsharing and the Patient Protection and Affordable Care Act.

PMID- 24308082
TI  - Open source synthetic biology: problems and solutions.

PMID- 24308084
TI  - What's new?

PMID- 24308083
TI  - March-in rights under the Bayh-Dole Act: the NIH's paper tiger?

PMID- 24308085
TI  - The legacy of Archie Cochrane: what's in it for pediatric nurses?

PMID- 24308086
TI  - What is 'normal?' Evaluating vital signs.
AB  - PROBLEM: Vital sign (VS) assessment and monitoring are often routinely scheduled
      whether they are needed or not. This practice led pediatric nurse leaders to
      voice concerns about the frequency of VS at a National Summit for Pediatric and
      Adolescent Evidence-Based Practice. A search of databases yielded no direct
      evidence regarding frequency. However, we determined that before this question
      could be adequately addressed, we first needed answers to two other important
      questions concerning normative values for this population and what constitutes
      significant change in VS. CLINICAL QUESTIONS: Among pediatric patients 1 to 5
      years of age, 1) what are "normal" VS parameters, and 2) what is a significant
      change in VS? METHOD: Additional searches, including a hand search, yielded five
      systematic reviews, one case-control study, five descriptive studies, and eight
      textbooks on normative values for children. Additionally, six articles on
      pediatric early warning signs (PEWS) were also reviewed. FINDINGS: Systematic
      reviews agree that vital signs are ill-defined and are a poor indicator of
      physical deterioration in young children. Normative VS tables are inconsistent
      and sometimes contradictory. Change parameters in the PEWS literature also lacked
      consistency. There is scarcity of high-quality, consistent research on normative
      VS values for children. Additionally, there is a lack of evidence to guide the
      frequency of assessments and use of behavioral and physiologic indicators of
      decline in young hospitalized children. This points to opportunities for further
      research in these areas. Clinicians need VS guidelines based on research to guide
      their clinical decision making and interventions.

PMID- 24308087
TI  - Children's perceptions of injuries: a qualitative study in Sweden.
AB  - To understand one of the major public health problems for children, it is
      important to consider the children's perspective. The purpose of this qualitative
      study was to explore, describe, and categorize children's perceptions of injury
      severity and children's explanations of the injuries they experience. A total of
      29 students from six randomly selected schools were interviewed in age groups of
      9, 13, and 17 years. Manifest content analysis according to Graneheim and Lundman
      (2004) was used to categorize children's own statements. Need of medical
      attention, long-term consequences, and familiarity with the injury risk situation
      were identified as important determinants of children's perception of injury
      severity. Three categories emerged from children's explanations of their
      injuries: "Because of Me" (beliefs, lack of concentration, health conditions, and
      lack of awareness of risk), "Because of the Situation" (rain, ice, wind, animals,
      inanimate objects, constructions, and the children's games), and "Just
      Inexplicable" to the children. Findings suggest that children have a wide
      perception of injury severity and that children's beliefs of injury causation, as
      well as children's familiarity with injury risk situations, need to be considered
      in future studies focusing on the development of childhood injury prevention
      strategies. Additionally, results suggest that sometimes children cannot or do
      not want to explain their injuries.

PMID- 24308088
TI  - The lived experience of parenting a child with autism in a rural area: making the
      invisible, visible.
AB  - This qualitative study explored the lived experiences of parents parenting a
      child with autism while living in a rural area. The philosophy of hermeneutic
      phenomenology was used to guide this inquiry, and interviews of 26 families
      served as primary data. Thematic statements were isolated using van Manen's
      (1990) selective highlighting approach. "Making the invisible, visible" emerged
      as the essence of the parents' experience. Parents shared that although autism
      was an invisible disability, they in fact made it visible in their constant
      battles to ensure their child received the best quality of life. The major themes
      of this essence included a) he's not the Rain Man, b) society's lack of knowledge
      and understanding, and c) doing it on our own. Findings from this study may be
      used to guide program development that is concerned with improving the quality of
      life of families of children with autism living in rural areas.

PMID- 24308089
TI  - Satisfaction of nurses with the Withdrawal Assessment Tool-1 (WAT-1).
AB  - BACKGROUND: Use of opioids and benzodiazepines in critically ill children results
      in an increased risk of withdrawal syndrome requiring the pediatric nurse to
      accurately assess the patient's clinical state. A valid and reliable pediatric
      withdrawal assessment tool could be of considerable value to improve nursing
      care. OBJECTIVE: To evaluate nurses' satisfaction with a new pediatric assessment
      tool, the Withdrawal Assessment Tool-1 (WAT-1). METHODS: Forty-one Pediatric
      Intensive Care Unit (PICU) and 27 Pediatric Intermediate Care Unit (PIMC) staff
      participated in a pre- and post-implementation survey. The survey looked at
      confidence in assessment skills, perception of communication about withdrawal,
      and satisfaction with nursing care of the child undergoing withdrawal syndrome.
      Staff were surveyed, completed online education about the WAT-1, and then
      repeated the survey after six months of clinical use. RESULTS: Overall confidence
      in assessment changed very little. There was improvement in the perception of
      communication (p = 0.005) as well as satisfaction with care provided (p =
      0.00002) after implementation of the WAT-1. In particular, satisfaction with
      nursing documentation of withdrawal syndrome improved significantly (p =
      0.00002). CONCLUSIONS: The WAT-1 improves nurses' satisfaction with their care of
      children undergoing withdrawal syndrome, in particular, their documentation of
      the level of withdrawal symptoms.

PMID- 24308090
TI  - Understanding the clinical handoff perspective of pediatric emergency nurses.
AB  - In 2007, The Joint Commission began requiring health care organizations to
      develop and implement a standardized approach to clinical handoff. The goal is to
      improve patient safety across the health care continuum. While accurate and
      complete handoff communication is essential in all areas of patient care, it is
      of critical importance where patients require the most complex care, such as in
      the emergency department. This quality improvement study used a focus group to
      begin to understand the clinical handoff perspective of pediatric emergency
      nurses. Eight nurses of varying levels of practice who work a variety of shifts
      participated to explore the clinical handoff process in the emergency department
      of a pediatric teaching hospital. Perceptions and beliefs regarding the process
      of clinical handoff (who is involved, what variations exist, where they occur)
      and barriers to the clinical handoff process were explored. Recurring themes
      included provider-directed handoff, interruptions--impediment to care, and
      envisioning the ideal process.

PMID- 24308091
TI  - Building quality improvement evidence.

PMID- 24308092
TI  - Pulse oximetry screening for critical congenital heart disease in the newborn.

PMID- 24308093
TI  - Watery discharge from the neck ... now that is strange!

PMID- 24308094
TI  - Speaking up for children undergoing procedures: the ONE VOICE approach.

PMID- 24308095
TI  - The evolution of obstructive sleep apnea (OSA) treatment and monitoring.

PMID- 24308096
TI  - Hold high your torch.

PMID- 24308097
TI  - Maxillomandibular advancement surgery as alternative to continuous positive
      airway pressure in morbidly severe obstructive sleep apnea: a case report.
AB  - Obstructive sleep apnea syndrome (OSAS) is a sleep-related breathing disorder,
      characterized by disrupted snoring and repetitive upper airway obstructions. Oral
      appliance therapy is an effective alternative to continuous positive airway
      pressure (CPAP) and is especially effective in mild and moderate OSAS cases.
      Successful oral appliance therapy has been suggested as a predictor for
      successful maxillomandibular advancement (MMA) surgery in OSAS patients. MMA
      surgery has gained increasing popularity in this field since this procedure is
      associated with an enlargement of the entire velo-oro-hypopharyngeal airway. The
      authors present an unusual case of a CPAP-intolerant morbidly obese female (body
      mass index (BMI) = 40) with morbidly severe OSAS (apnea-hypopnea index (AHI) =
      139, lowest oxyhemoglobin saturation level = 73%), who underwent a successful
      combination of MMA surgery, a modified genioplasty and cervicomental liposuction
      after oral appliance therapy. The post-surgical AHI was 6, and the lowest
      oxyhemoglobin saturation level increased to 86%. The authors suggest that this
      surgical combination should be seriously considered in obese patients with severe
      OSAS and CPAP intolerance.

PMID- 24308098
TI  - Craniocervical posture and trigeminal nerve mechanosensitivity in subjects with a
      history of orthodontic use: a cross-sectional study.
AB  - The purpose of the study was to evaluate whether, in asymptomatic subjects, there
      are differences in: (i) head posture while sitting and standing still and (ii)
      trigeminal nerve mechanosensitivity, between those who have a history of using
      orthodontics and those who do not. The sample consisted of 72 subjects (21 +/-
      2.14 years): one group who had used orthodontics in the past (n = 37), and
      another group who had not had previous orthodontic treatment (n = 35). The
      authors measured the CranioVertebral Angle (CVA) while the subject was sitting
      and standing still by means of lateral photographs, and the pressure pain
      threshold (PPT) of the trigeminal nerve. The orthodontics group showed a more
      upright position of the head when sitting compared to the non-orthodontics group,
      with the difference being statistically significant (ANOVA test; p < 0.001; F1,70
      = 16.705; R2 = 0.19), but not for the standing position (p = 0.538). The values
      of the PPT in the trigeminal nerve (supraorbital-V1, infraorbital-V2 and
      mandibular-V3) were lower on both sides (dominant and nondominant) in the non
      orthodontics group. The between-group comparison (ANOVA test) showed
      statistically significant differences for the trigeminal nerve PPT in its
      different branches (V1 p = 0.001; F1,70 = 13.012; R2 = 0.15) (V2 p = 0.004; F1,70
      = 9.103; R2 = 0.11) (V3 p = 0.005; F1,70 = 8.228; R2 = 0.10). Based on these
      observations, it was concluded that subjects with a history of orthodontic use
      show a better sitting craniocervical posture and mechano-sensitivity of the
      trigeminal nerve branches compared to the group that had not used orthodontics in
      the past.

PMID- 24308099
TI  - Smoothness of molar movement during gum chewing in children with primary
      dentition.
AB  - The purpose of this study was to test the null hypothesis that molar movement
      during gum chewing in children with primary dentition is as smooth as in adults.
      Twenty-two healthy children with primary dentition and 23 healthy adult females
      participated in this study. Mandibular movement during gum chewing was recorded
      using an optoelectronic analysis system with six degrees-of-freedom at 100 Hz,
      and 10 cycles were selected for analysis. Normalized jerk cost (NJC) at the
      incisors and working and balancing molars were calculated in each phase (i.e.,
      opening, closing and occlusal level phases) for each chewing cycle. The NJC of
      the working side molar in children was larger than in adults in both the opening
      and occlusal phases. Inter-individual variances of the NJC in each phase in
      children and adults were smaller than corresponding intra-individual variances,
      except for the NJC during the occlusal phase of adults for the working and
      balancing side molars. The inter- and intra-individual variances of the NJC
      during the closing phase were the smallest in each phase for both children and
      adults. This indicates that the jaw movements of children with primary dentition
      are more variable, less smooth, and faster than that of adults.

PMID- 24308100
TI  - Volumetric wear of various orthotic appliance materials.
AB  - The purpose of this study was to compare the resistance to wear of six commonly
      used orthotic appliance materials. These materials were: SR Ivocap (Ivoclar
      Vivadent, Inc., Amherst, NY), Eclipse (Dentsply International, York, PA), ProBase
      (Ivoclar Vivadent), Valplast (Valplast International Corp., Oceanside, NY), Impak
      (CMP Industries LLC, Albany, NY), and Clearsplint (Astron Dental Corp., Lake
      Zurich, IL). Twelve cylindrical specimens of each material were fabricated per
      manufacturer instructions. Occlusal wear was simulated in a custom-made wear
      simulator with each specimen receiving four wear scars in a two-body wear
      simulation using a 1.5 mm tungsten-carbide tipped stylus at 40 newtons for 2500
      cycles at 1 Hz, while immersed in 37 degrees C distilled water (n = 48). The
      specimens were evaluated before and after wear testing using a three-dimensional
      (3D) noncontact profilometer (Proscan 2000, Scantron Corp., Eagan, MN). A mean
      change in volume was determined for each orthotic material. Results found that
      Clearsplint material displayed the greatest amount of volume loss/wear, while SR
      Ivocap, Eclipse, and ProBase materials had the least amount of wear. Valplast and
      Impak performed more moderately. Based upon this wear knowledge, practitioners
      are able to more reliably choose the appliance material necessary for their
      various patients.

PMID- 24308101
TI  - Temporomandibular dysfunction: internal derangement associated with facial and/or
      mandibular asymmetry.
AB  - The aim of this study was to observe the association between facial and/or
      mandibular asymmetry and internal derangement of the temporomandibular joint
      (TMJ) in patients with temporomandibular dysfunction (TMD). The sample consisted
      of 17 patients with facial and/or condylar-mandibular asymmetry who had signs and
      symptoms of TMD. They were evaluated by means of clinical examination, panoramic
      radiography, nuclear magnetic resonance (NMR), and in some cases, computed
      tomography (CT) and scintigraphy. All patients with facial and/or condylar
      mandibular asymmetry had TMJ disc displacement (DD). The results of this study
      suggest a possible association between facial and/or condylar-mandibular
      asymmetry and DD. Based on these findings, it is important to consider the need
      for treating this disorder, particularly in growing patients, in order to prevent
      the generation of asymmetry, which is very difficult to treat once it sets in.

PMID- 24308102
TI  - Frequency of oral habits, dysfunctions, and personality traits in bruxing and
      nonbruxing children: a comparative study.
AB  - The aim of the current study was to compare personality traits, presence of oral
      myofunctional dysfunctions, and other parafunctional habits in bruxing and
      nonbruxing children. Fifty-four patients aged 10 to 15 years were seen at the
      Comprehensive Pediatric Dental Clinic and examined by dentists using the RDC/TMD;
      speech therapists and psychologists were included in the study. Patients were
      divided into two groups: bruxing (A) and nonbruxing (B). Mean age was 13.1 years,
      S.D. 1.6. No significant differences in age or gender were found between groups.
      Group A comprised 44.44% of the population and showed a high frequency of middle
      conscientiousness scores and low frequency of low neuroticism scores. Presence of
      TMD, unilateral chewing, and high tongue tip position at rest were all
      significantly higher. Frequency of oral habits was higher in bruxers, who showed
      significantly increased gum chewing, and lip, cheek, and object biting compared
      to nonbruxing controls. Bruxism is considered a risk factor for temporomandibular
      dysfunction (TMD).

PMID- 24308103
TI  - Efficacy of massage treatment technique in masseter muscle hardness: robotic
      experimental approach.
AB  - The study aimed to clarify the masseter muscle hardness in patients with
      myofascial pain, to examine their changes after massage, and to analyze whether
      the hardness can be an index for massage treatment. Sixteen patients with
      myofascial pain (12 with unilateral and 4 with bilateral masseter muscle pain)
      and 24 healthy volunteers were enrolled in this study. The masseter hardness
      between patients and the healthy volunteers was compared. The changes in the
      hardness in patients after massage were examined. The relation of the hardness
      with massage regimens and efficacies was analyzed. There was a significant right
      and-left difference of the hardness in patients, although there was no difference
      in the healthy volunteers. The hardness decreased after massage. The pretreatment
      asymmetry index of the hardness showed a significant correlation with the massage
      pressure. It was concluded that there was a significant difference between the
      right and left masseter hardness in patients with myofascial pain. After massage
      treatment, the masseter hardness and right-and-left difference decreased. The
      hardness may be an index for determining the massage pressure.

PMID- 24308104
TI  - Prescriptive proprioceptive insoles and dental orthotics change the frontal plane
      position of the atlas (C1), mastoid, malar, temporal, and sphenoid bones: a
      preliminary study.
AB  - The purpose of this series of case studies was to determine if the frontal plane
      position of the cranial bones and atlas could be altered using dental orthotics,
      prescriptive insoles, or both concurrently. The cranial radiographs of four
      patients were reviewed for the study. Three of the patients were diagnosed as
      having a temporomandibular joint (TMJ) dysfunction and a preclinical clubfoot
      deformity. The fourth patient was diagnosed as having a TMJ dysfunction, a
      preclinical clubfoot deformity and a Catetgory II sacral occipital subluxation,
      as designated in the chiropractic's Sacro Occipital Technique (SOT). Each patient
      had a series of four cranial radiographs taken using a modified orthogonal
      protocol. In two patients, improvement towards orthogonal was achieved when using
      both prescriptive dental orthotics and prescriptive insoles concurrently.
      Improvement towards orthogonal was less apparent when using only the prescriptive
      dental orthotic. No improvement or a negative frontal plane shift was noted when
      using only the prescriptive proprioceptive insoles. In the third patient, the
      frontal plane position of the cranial bones and atlas increased (away from
      orthogonal) when using the generic proprioceptive insoles alone or in combination
      with a prescriptive dental orthotic. In the fourth patient, the frontal plane
      position of the cranial bones improved using the dental orthotic. However, the
      proprioceptive insoles, when used alone or in combination with the dental
      orthotic, increased the frontal plane position of the cranial bones and atlas.
      This study demonstrates that changes in the frontal plane position of the cranial
      and atlas bones can occur when using proprioceptive insoles and/or dental
      orthotics.

PMID- 24308105
TI  - Synovial chondromatosis of the temporomandibular joint: a case report and
      literature review.
AB  - Synovial chondromatosis (SC) is a pathologic condition in which mesenchymal
      tissue rests in a given synovial membrane undergo a metaplastic process,
      ultimately producing and secreting cartilaginous bodies into the joint space. It
      is more commonly discussed in the orthopedic literature, since the axial skeleton
      is the most frequently affected. Although rare, it does occur within the
      temporomandibular joint (TMJ), with approximately 100 cases previously being
      described. Within the TMJ, its presentation can be variable, though most cases
      will show it to be unilateral with fixed and/or loose cartilaginous bodies
      confined to the superior joint space. Clinically, patients may present with
      symptoms similar to that of an internal derangement disorder, including pain,
      clicking, tenderness, functional limitations, and swelling. A thorough history
      and physical examination, along with proper radiographic examination, are
      paramount in properly diagnosing SC. Treatment options consist of arthroscopy,
      arthrotomy with synovectomy, excision of cartilaginous bodies, and possible
      discectomy. In the current paper, the authors describe the presentation,
      diagnosis, and surgical management of a SC case involving the right TMJ in a 31
      year-old Caucasian female.

PMID- 24308106
TI  - Nurse safety.

PMID- 24308107
TI  - Water treatment for hemodialysis: an update.
AB  - While nurses may not routinely service the water treatment system or mix the
      dialysate, they are responsible for understanding all of the clinical
      ramifications of water treatment and dialysate preparation for hemodialysis as a
      part of the entire dialysis treatment picture. Although the water treatment
      system has historically been in the technicians' domain, knowing the technical
      aspects is important for the entire team to work together to ensure patient
      safety and well-being. This article describes the composition of water treatment
      systems for hemodialysis, as well as the monitoring and testing necessary to
      assure that both water and dialysate are safe for patient use.

PMID- 24308108
TI  - Non-pharmaceutical fatigue interventions in adults receiving hemodialysis: a
      systematic review.
AB  - Fatigue is common for individuals receiving hemodialysis and can lead to
      decreased physical function, quality of life, and survival. Because fatigue is
      frequently reported as bothersome, nurses must discover effective ways to assist
      patients to manage this symptom. The purpose of this systematic review was to
      examine the effectiveness of non-pharmacologic interventions used to minimize
      fatigue. Interventions found to significantly reduce fatigue included exercise
      and Eastern medicine-based therapies.

PMID- 24308109
TI  - Calciphylaxis: a devastating complication of derangements of calcium-phosphorus
      metabolism--a case report and review of the literature.
AB  - Calciphylaxis is a rare and potentially devastating condition also referred to as
      uremic gangrene syndrome, calcific uremic arteriolopathy, metastatic
      calcification, and uremic small-vessel disease that can present in patients with
      end stage renal disease. This article reports a case of a 38-year-old African
      American female on peritoneal dialysis for six years with a known history of non
      adherence with diet, medications, and prescribed peritoneal dialysis treatment
      regimen. At her monthly clinic visit, the patient complained of burning sensation
      in the fingers of both hands with limited fine motor movement due to edema and
      severe pain. A presumptive diagnosis of calciphylaxis led to hospital admission
      with confirmation by X-ray of her hands. The patient was switched to hemodialysis
      with low calcium dialysate, aggressive reduction in phosphorus, diet counseling,
      use of cinacalcet, and six weeks of intravenous sodium thiosulfate infusion with
      hemodialysis treatments. The patient's condition improved with resolution of
      symptoms. This case was chosen based on the rarity of a calciphylaxis
      presentation and paucity of knowledge regarding diagnosis and treatment.

PMID- 24308110
TI  - Viewing an educational video can improve phosphorus control in patients on
      hemodialysis: a pilot study.
AB  - The objective of this single-arm interventional pilot study was to determine
      whether viewing an educational video about phosphorous and phosphorous control by
      patients on hemodialysis was associated with improved phosphorous values and
      improvement in knowledge and attitudes about the topics presented. METHOD: An
      educational video was shown to 150 patients at 16 dialysis centers. The change in
      serum phosphate levels before and after the viewing of an educational video was
      evaluated. RESULTS: Mean phosphorous levels for patients were lower in the month
      after viewing the educational video compared to their values over the three
      months before the video was shown (6.35 versus 6.82 g/dL). This difference was
      statistically significant on a per patient basis (-0.47 g/dL, p = 0.0006). Of
      these patients, all with phosphorus levels outside of the normal range (3.5 to
      5.5 mg/dL) before viewing the video, 28.4% had phosphorus levels within the
      normal range within a month after viewing the video. CONCLUSION: Patients on
      hemodialysis who watched an educational video had improved phosphorous levels in
      the month after viewing the video when compared to phosphorus levels over the
      three months before the video was shown. The video intervention has the
      advantages of being simple, low-cost, and easy to implement, and is associated
      with improved phosphorous levels in patients undergoing hemodialysis. The video
      increased patient compliance with recommended self-care regimens.

PMID- 24308111
TI  - Does blood volume monitor use decrease episodes of intradialytic hypotension in
      chronic hemodialysis treatments?

PMID- 24308112
TI  - From critical care nurse to nephrology nurse in the intensive care unit.

PMID- 24308113
TI  - Forearm compartment syndrome in a patient on hemodialysis following failure of an
      arteriovenous fistula.

PMID- 24308114
TI  - Strategies for disaster readiness.

PMID- 24308115
TI  - Designing for safety and beauty.

PMID- 24308116
TI  - Embattled survivors give lifesaving advice.

PMID- 24308117
TI  - Rising above Iowa's 2008 flood.

PMID- 24308118
TI  - Catholic Charities, Baton Rouge: teams take their expertise on the road.

PMID- 24308120
TI  - For long-term care, readiness gaps abound.

PMID- 24308119
TI  - Connections matter when disaster hits.

PMID- 24308121
TI  - Good planning pays off for PACE.

PMID- 24308123
TI  - Interview with Nicole Lurie, MD. Official's focus shifts to the vulnerable at
      home. Interview by Marie Rohde.

PMID- 24308122
TI  - Preparedness must permeate health care: yet still has a long way to go.

PMID- 24308124
TI  - Allocating resources--a wicked problem.

PMID- 24308125
TI  - Combating global warming: Healthy climate, healthy people.

PMID- 24308126
TI  - New survey: mission leaders respond Executive Summary of the 2013 CHA Mission
      Leader Survey.

PMID- 24308127
TI  - Aligning cultures, vision and values: hitting all the keys.

PMID- 24308128
TI  - Preparing communities to be healthy, resilient.

PMID- 24308129
TI  - Affordable Care Act: we can do this.

PMID- 24308130
TI  - Polst: a portable plan for care.

PMID- 24308131
TI  - The best may come in fallow time.

PMID- 24308132
TI  - Staving off loneliness.

PMID- 24308133
TI  - An incomparable journey.

PMID- 24308134
TI  - Parkinson's disease: my nemesis, my teacher.

PMID- 24308135
TI  - Back to the basics.

PMID- 24308136
TI  - Therapy, ADLs top RAI manual update list.

PMID- 24308137
TI  - [Therapeutic aggressiveness and "investigational" aggressiveness: even fight!].

PMID- 24308138
TI  - [Cognitive impairment in elderly patients: what to do in primary care?].
AB  - In Switzerland, each year there are about 25000 new patients suffering from
      dementia (one new case every 20 minutes!). Currently, recognition of cognitive
      impairment and dementia diagnoses remain essentially based on clinical features.
      For the primary care provider, a 4-step approach based on a) history, b)
      collateral information provided by a knowledgeable relative, c) a standardized
      brief cognitive screening instrument, and d) simple laboratory tests will
      identify most older persons suffering from dementia. Unclear situations benefit
      from an assessment in a memory clinic.

PMID- 24308139
TI  - [Antiplatelet agents and older patients: which drugs and what evidence?].
AB  - Antiplatelet drugs are a cornerstone for the management of all atherosclerosis
      related conditions, increasingly frequent with advanced age. Associations of
      antiplatelet drugs increase the bleeding risk and the overall net clinical
      benefit should be carefully assessed. In the absence of recommendations made
      specifically for the elderly practical suggestions can be inferred from subgroup
      analyses of large trials. The association of two antiplatelet agents should be
      limited to acute coronary syndromes for a maximum of one year, avoiding prasugrel
      in 75 years and older patients, and to coronary angioplasties for a minimum
      duration depending on the type of stent. In elderly patients with atrial
      fibrillation and ischemic heart disease more than one year after coronary
      stenting, a vitamin K antagonist alone is usually sufficient.

PMID- 24308140
TI  - [Geriatric assessment in old patients candidate to transcatheter aortic
      implantation].
AB  - Aortic stenosis mostly occurs among old-old patients. Once symptoms appear,
      prognosis is guarded, with 2-year mortality as high as 50%. Transcatheter Aortic
      Valve Implantation (TAVI) is a new therapeutic option in patients at very high
      surgical risk, who are mostly older persons. However, TAVI is associated with
      some complications, and patient selection remains a challenge. Comprehensive
      geriatric assessment (CGA) identifies patients with medical and functional
      problems likely to affect the TAVI post-operative course. Collaboration between
      cardiologists and geriatricians will likely become a standard approach to enhance
      the assessment of these frail patients and identify those most likely to benefit
      from TAVI.

PMID- 24308141
TI  - [Clostridium difficile infections, specific issues in the elderly].
AB  - Clostridium difficile is a well-established cause of infectious nosocomial
      diarrhea in adults. Each time diarrhea is observed in a patient receiving
      antibiotic treatment, Clostridium colitis should be suspected; diagnosis should
      be confirmed by the identification of toxin in the patient's stools. Its
      incidence is increasing due to growing use of several classes of antibiotics, and
      is associated with a high relapse rate and a significant case-fatality rate. The
      elderly are particularly at risk for this type of infection. Recent developments
      include the occurrence of epidemics in restricted communities and settings and
      the appearence of new virulent strains of this pathogen (especially PCR Ribotype
      027). Vancomycin should be preferred over metronidazole in severe cases of
      diarrhea. New treatments are currently being tested and evaluated. Prevention
      remains a priority; high standards of hygiene and careful attention to the
      judicious prescription of antibiotics are crucial in this regard.

PMID- 24308142
TI  - [Bullous pemphigoid: a cutaneous disorder to be known in aging persons].
AB  - Bullous pemphigoid is a rare autoimmune muco-cutaneous disorder involving
      particularly aged adults. Its incidence may be underestimated. Recent studies
      show the various clinical presentations that may delay diagnosis up to several
      years in absence of typical bullous presentation. Diagnosis such as skin adverse
      event or infection should be quickly eliminated and the autoimmunity confirmed
      with skin and blood immunology and pathology analysis. Any chronic pruritis or
      persisting blister in old people should lead to the diagnosis procedures of a
      bullous pemphigoid.

PMID- 24308143
TI  - [Drug-induced adverse events in the elderly: a traveler's guide].
AB  - Elderly people are prone to drug-induced adverse events (AEs), which often
      manifest as an atypical clinical picture. The differential diagnosis of any new
      symptom or alteration in the general state of health in the elderly must,
      therefore, include AEs. This article offers a practical tool designed to help
      clinicians to rapidly identify which drugs may induce which kind of frequent
      symptoms or syndromes.

PMID- 24308144
TI  - [Identification of elderly material and financial abuse].
AB  - Elder abuse and in particular material and financial exploitation involving the
      misappropriation of the older person's money or property is common but rarely
      identified or managed in clinical practice. It has a direct impact on quality of
      life, health and social status. Our aim is to assist clinicians by summarizing
      this frequently unrecognized problem. We discuss risk factors, alerting signs,
      clinical manifestations, and specific questions that can be used for screening
      purposes as well as intervention strategies preferably in the context of a
      multidisciplinary team.

PMID- 24308145
TI  - [Poliomyelitis: eradication questioned].

PMID- 24308147
TI  - [Twenty-four French intellectuals claim that animals are not beasts].

PMID- 24308148
TI  - [Our air is carcinogenic; Proust was asthmatic].

PMID- 24308149
TI  - [Electronic intimacy].

PMID- 24308150
TI  - Who is the aesthetic consumer?

PMID- 24308151
TI  - Cosmeceuticals for men.
AB  - The demand for topical products capable of preventing aging or delivering
      cosmetic improvement to the male skin is growing. Companies are marketing
      products that are labeled "for men." Nevertheless, there is no consensus on which
      properties these products should possess. This article aims to develop a rational
      approach to men's cosmeceuticals based on anatomic and physiologic features of
      the male skin without neglecting behavioral idiosyncrasies when relevant. A
      review of the literature for skin gender singularities was used to determine the
      needs of male skin and subsequently to postulate how cosmeceuticals could fulfill
      these needs. Cosmeceutical ingredients capable of reversing sun-induced
      alteration are of particular benefit for men. Adapting cosmetic treatment to male
      grooming routines increases compliance. Shaving presents an opportunity to
      deliver cosmeceuticals for men. The marketing of skin care products for men is
      evolving and becoming seemingly complex; further research is warranted.

PMID- 24308152
TI  - Botulinum toxin type A reconstituted in lidocaine with epinephrine for facial
      rejuvenation: results of a participant satisfaction survey.
AB  - To assess the feasibility, safety, and lack of inferiority of reconstituting
      botulinum toxin type A (BTX-A) in 1% lidocaine hydrochloride with epinephrine
      1:100,000, 181 participants were asked to complete a satisfaction survey 3 to 6
      months after treatment with the reconstituted formulation for facial
      rejuvenation. The addition of lidocaine was believed to achieve an immediate
      paralyzing effect on the injected muscles, and the addition of epinephrine was
      hypothesized to minimize diffusion to adjacent muscles. Participants were treated
      in the areas of the forehead and glabella, as well as the orbicularis oculi,
      orbicularis oris, and procerus muscles, in varying doses (10-60 U). Fifty-eight
      percent (91/157) of participants reported being more satisfied with BTX-A
      reconstituted in 1% lidocaine with epinephrine 1:100,000, with 85.7% (78/91) of
      these participants reporting that the immediate results made the formulation
      superior; 35.7% (56/157) were indifferent and 6.4% (10/157) reported that the
      modified formulation did not work better. The injection of BTX-A reconstituted in
      1% lidocaine with epinephrine 1:100,000 presented no increased adverse effects
      (AEs), no decrease in pharmacologic potency, immediate feedback to the clinician,
      and higher satisfaction for the participants who previously had been treated with
      BTX-A reconstituted in unpreserved saline. Botulinum toxin type A reconstituted
      in 1% lidocaine with epinephrine 1:100,000 may increase the duration and efficacy
      of this widely used toxin.

PMID- 24308153
TI  - Absorbable poliglecaprone 25 sutures for both subcutaneous and transepidermal
      closure: a cosmetically and economically appealing option.
AB  - The majority of dermatologic surgeons close surgical defects using absorbable
      sutures to approximate deep subcutaneous tissue and nonabsorbable sutures to
      close the epidermal tissue. However, the absorbable monofilament poliglecaprone
      25 can serve as the sole suture material in closing deep surgical defects
      involving subcutaneous and epidermal tissue with the benefits of providing
      aesthetically pleasing outcomes, possibly due to the material's low tissue
      reactivity and clear colorless appearance, and cost-effectiveness. We discuss the
      estimated cost savings per procedure when using poliglecaprone 25. Additional
      advantages include increased versatility, ease of handling, and convenience. Some
      disadvantages include a slight stiffness of the suture material, which may
      require a surgeon to make minor adjustments to his/her knot tying technique, as
      well as a transparent appearance that may make suture removal more challenging
      when using the undyed version of the suture material. However, the many benefits
      of using poliglecaprone 25 for closure of surgical defects outweigh the few
      disadvantages.

PMID- 24308154
TI  - RITA inhibits growth of human hepatocellular carcinoma through induction of
      apoptosis.
AB  - RBP-J-interacting and tubulin-associated (RITA) is a novel RBP-J-interacting
      protein that downregulates Notch-mediated transcription. The current study
      focuses on the antitumor effect of RITA in human hepatocellular carcinoma (HCC)
      and aims to explore its molecular mechanism. Thirty paired HCC and adjacent non
      tumoral liver samples were analyzed by real-time quantitative reverse
      transcriptase polymerase chain reaction (qRT-PCR). RITA overexpression was
      induced by transfection of a pcDNA3.1-Flag-RITA plasmid into HepG2 cells. RITA
      knockdown was achieved by siRNA transfection. mRNA and protein expression of
      target genes were quantified by qRT-PCR and Western blotting, respectively. Cell
      proliferation and apoptosis were measured using MTT assay and flow cytometry. Our
      results demonstrate that adjacent nontumoral liver samples exhibited increased
      RITA expression compared to HCC tissues (p < 0.05); RITA levels were associated
      with tumor differentiation status. Overexpression of RITA suppressed cell
      proliferation and promoted early apoptosis, while its silencing promoted cell
      growth dramatically (p < 0.05). RITA overexpression upregulated p53 and reduced
      cyclin E levels, whereas silencing of RITA had the opposite effect on p53 and
      cyclin E expression. Our in vitro results represent the first evidence that RITA
      might suppress tumor growth and induce apoptosis in HCCs, and may be a potent
      antitumoral agent for HCC treatment that deserves further exploration.

PMID- 24308155
TI  - Enhancement of antitumor activity by combination of tumor lysate-pulsed dendritic
      cells and celecoxib in a rat glioma model.
AB  - Using dendritic cell (DC)-based vaccines for treatment of gliomas has emerged as
      a meaningful and feasible treatment approach for inducing long-term survival, but
      this approach so far has failed to generate significant clinical responses. In
      the present study, we demonstrated that glioma lysate-pulsed DCs in combination
      with celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, showed more
      significantly enhanced antitumor activity with increased apoptosis of tumor
      cells, reduced neovascularization, and developed a strong cytotoxic T lymphocyte
      (CTL) response in tumor-bearing rats. Celecoxib may reduce production of
      prostaglandin E2 and modulate the balance between T helper 1 (Th1) cytokines and
      T helper 2 (Th2) cytokines by increasing the pivotal Thl cytokine interleukin-12
      and reducing Th2 cytokine interleukin-10. Taken together, our results
      demonstrated that selective inhibition of COX-2 using celecoxib combined with DC
      based immunotherapy could act as an important novel strategy for improving future
      treatment of malignant gliomas.

PMID- 24308156
TI  - BTG2 overexpression increases the radiosensitivity of breast cancer cells in
      vitro and in vivo.
AB  - Antiproliferative gene B-cell translocation gene, member 2 (BTG2) is a member of
      the BTG/TOB antiproliferative gene family. In this study, we investigated the
      effect of BTG2 gene overexpression on the radiosensitivity of breast cancer cells
      in vitro and in vivo. Results show that in human breast cancer cell line MCF-7
      stably overexpressing BTG2 gene, cell sensitivity to ionizing radiation
      increased. The MCF-7-BTG2 cells were more susceptible to radiation-caused
      apoptosis with decreased cyclin B1, cyclin D1, Ku70, FEN-1, and XRCC1 protein
      expression as well as increased BAX protein expression. The findings indicate for
      the first time that BTG2 can improve the radiosensitivity of breast cancer cells
      by affecting cell cycle distribution, enhancing radiation-induced apoptosis, and
      inhibiting DNA repair-related protein expression.

PMID- 24308157
TI  - The role of HOXA9 in human laryngeal squamous cell carcinoma.
AB  - The present study was performed to investigate the expression of HOXA9 in human
      laryngeal squamous cell carcinoma and its possible roles in the progression. The
      levels of HOXA9 mRNA and protein were evaluated in human laryngeal squamous cell
      carcinoma. Hep-2 cells were transfected with h-HOXA9-siRNA. CCK-8 was used to
      analyze cell proliferation. Flow cytometry (FCM) was used to analyze cell cycle.
      The mobility of cells was tested by transwell migration assay. The expression of
      HOXA9 in laryngeal squamous cell carcinoma was significantly higher than normal
      mucosa tissues. In in vitro experiments, downregulation of HOXA9 strongly
      inhibited cell growth in Hep-2 by arresting cells in G1 phase (p < 0.05).
      Transwell migration assay showed that more HOXA9-negative cells migrated to the
      lower side of the membrane than positive ones (p < 0.01). HOXA9 acts as an
      oncogene in laryngeal squamous cell carcinoma. It could promote the proliferation
      and migration of Hep-2 cells.

PMID- 24308158
TI  - Inhibition of tumor growth and alteration of associated macrophage cell type by
      an HO-1 inhibitor in breast carcinoma-bearing mice.
AB  - Heme oxygenase-1 [HO-1, also called heat shot protein 32 (HSP32)] can
      specifically metabolize heme to carbon monoxide, biliverdin, and ferrous iron and
      plays an important role in the processes of anti-inflammation, tissue protection,
      and antioxidative stress reaction. It has been reported that HO-1 can promote
      tumorigenesis and metastasis of many tumors. However, the detailed mechanisms of
      how HO-1 affects tumor progress are not clear. Here, we used ZnPPIX (a specific
      inhibitor of HO-1) to evaluate its potential effects on mouse breast cancer and
      tumor-associated macrophages (TAMs). We found out that mouse 4T1 breast cancer
      growth can be effectively suppressed through inhibition of HO-1 in vitro and in
      vivo. Moreover, in the 4T1 mouse model, when HO-1 was suppressed in TAMs,
      alternatively activated macrophages (M2 type) switched to classically activated
      macrophages (M1 type). In conclusion, 4T1 breast cancer growth was modulated by
      HO-1 expression. Furthermore, inhibition of HO-1 may induce tumor-associated
      immune response by activating TAMs' alternative proliferation. These data suggest
      that HO-1 may be an important target of breast cancer treatment.

PMID- 24308159
TI  - Prolonged disease stability with trabectedin in a heavily pretreated elderly
      patient with metastatic leiomyosarcoma of the thigh and renal failure: a case
      report and review of the literature.
AB  - Leiomyosarcoma represents about 24% of all soft tissue sarcomas and can originate
      from retroperitoneum, uterus, or extremities. Adequate local control may be
      achieved with surgery and radiotherapy. In the presence of unresectable
      metastases either doxorubicin- or gemcitabine-based chemotherapy is the standard
      of treatment. Nevertheless, prognosis remains poor regardless of the selected
      chemotherapy regimen, and new effective therapeutic agents for patients with
      advanced leiomyosarcoma are needed. Trabectedin, a promising new DNA-damaging
      agent with a mechanism of action that is different from that of traditional
      alkylating agents, is approved in Europe for the treatment of patients with
      advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or
      who are unsuited to receive these agents and in combination with pegylated
      liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum
      sensitive ovarian cancer. We present a case of a 76-year-old patient with
      progressive metastatic lung lesions from a previously resected primary
      leiomyosarcoma of the thigh and moderate renal failure, who achieved 17 months of
      disease stability during third-line treatment with trabectedin. Trabectedin was
      not associated with any cumulative toxicity and was consistently well tolerated
      for a total of 22 treatment cycles. Current evidence on trabectedin is also
      presented.

PMID- 24308160
TI  - Toward a national policy on long term care & statement to the Commisssion on Long
      Term Care.

PMID- 24308161
TI  - Report of the Commission on Long Term Care issued September 12, 2013.

PMID- 24308162
TI  - A guided tour of the nation's capitol: site of the 2013 NAHC Annual Meeting.

PMID- 24308163
TI  - Understanding Medicare premiums.

PMID- 24308164
TI  - Alzheimer's in those with Down's syndrome.

PMID- 24308165
TI  - Make your service monogrammed.

PMID- 24308166
TI  - Are you a professional writer? Conflicting testimonies.

PMID- 24308167
TI  - Breath wish. What's behind this persistent shortness of breath?

PMID- 24308168
TI  - Give a little; get a little. Improving your patient care connections.

PMID- 24308169
TI  - An EMS introduction to accountable care organizations. ACOs bring healthcare
      system partners together to deliver better care to certain types of patients.

PMID- 24308170
TI  - The hospital cooperative model for EMS. What are the benefits of bringing
      multiple hospitals together to deliver emergency medical services?

PMID- 24308171
TI  - MIH approach proves positive for Chicago CHF trial. Collaboration seems to be
      cutting readmissions, improving experiences.

PMID- 24308172
TI  - Infection control update: the emerging threat of CRE. A potential new superbug
      resists antibiotics.

PMID- 24308173
TI  - San Antonio Police Department launches tactical medic program. Specially trained
      officers can deliver emergency care until EMS takes over.

PMID- 24308174
TI  - Prehospital childbirth fetal complications. Part 2: what can go wrong, and how
      can you tell?

PMID- 24308175
TI  - A sentimental journey. Program helps grant last wishes.

PMID- 24308176
TI  - EMS in the National Park Service. Responders face myriad challenges when it comes
      to delivering patient care in our nation's parks.

PMID- 24308177
TI  - Dusting for fingerprints. How to reinforce the foundation of an EMS safety
      culture.

PMID- 24308178
TI  - Desk duty. Time to step away from a fascinating, rewarding field.

PMID- 24308179
TI  - [Effect of manual acupuncture stimulation of "Zusanli" (ST 36) on gastric
      motility, and SP and motilin activities in gastric antrum and nucleus raphe
      magnus in gastric hyperactivity and hypoactivity rats].
AB  - OBJECTIVE: To observe the changes of gastric motility and levels of substance P
      (SP) and motilin (MTL) in the gastric antrum and Nucleus Raphe Magnus (NRM) after
      manual acupuncture stimulation of "Zusanli" (ST 36) in gastric hyperactivity and
      hypoactivity rats, so as to analyze the role of NRM in acupuncture mediated
      adjustment of gastric motility. METHODS: Fifty SD rats were randomly and equally
      divided into control, gastric hyperactivity (G-Hypera) model, gastric
      hypoactivity (G-Hypoa) model, acupuncture + G-Hypera and acupuncture + G-Hypoa
      groups (10 rats/group). G-Hypera model was established by intravenous (tail vein)
      injection of Maxolon (0.5 mL/200 g) and G-Hypoa model established by intravenous
      injection of Atropin (0.5 mL/200 g), respectively. After insertion of acupuncture
      needles into bilateral "Zusanli" (ST 36), the needles were repeatedly manipulated
      at a frequency of about 2 Hz for 5 min. The intragastric pressure was recorded
      and analyzed using a physiological signal analysis system. The SP and MTL
      contents of gastric antrum were measured by ELISA, and SP and MTL immunoactivity
      of NRM was determined by immunohistochemistry. RESULTS: In gastric hyperactivity
      rats, compared with the control group, the intragastric pressure (not systolic
      frequency), SP and MTL contents in the gastric antrum and MTL immunoactivity of
      NRM were significantly increased (P < 0.05, P < 0.01), while SP immunoactivity of
      NRM was apparently decreased in the G-Hypera model group (P < 0.01). After
      acupuncture stimulation, the intragastric pressure, gastric SP and MTL contents,
      and MTL immunoactivity of NRM were all significantly down-regulated (P < 0.05, P
      < 0.01), and SP immunoactivity of NRM was markedly up-regulated (P < 0.01) in
      comparison with the model group. In gastric hypoactivity rats, compared with the
      control group, the intragastric pressure and gastric systolic frequency, gastric
      SP and MTL contents, and MTL immunoactivity of NRM were significantly decreased
      (P < 0.05, PF < 0.01), while SP immunoactivity of NRM was remarkably up-regulated
      in the G-Hypoa model group (P < 0.01). After acupuncture stimulation, the above
      mentioned 6 indexes were reversed significantly (P < 0.05, P < 0.01) in
      comparison with those of the model group. CONCLUSION: Acupuncture stimulation of
      "Zusanli" (ST 36) has an obvious bi-directional adjustment effect on gastric
      motility, which is closely associated with its functions in regulating gastric SP
      and MTL level and the expression of MTL and SP in the NRM of brainstem.

PMID- 24308180
TI  - [Effect of drug-paste separated moxibustion on expression of estrogen,
      progestogen and their endometrial receptor mRNA in rats with primary
      dysmenorrhea].
AB  - OBJECTIVE: To observe the effect of drug-paste separated moxibustion of "Mingmen"
      (GV 4) on the levels of serum estrogen (E2) and progesterone (P) and their
      endometrial receptor mRNA expression in rats with primary dysmenorrhea in order
      to investigate its mechanism underlying improvement of primary dysmenorrhea.
      METHODS: A total of 100 female SD rats were randomized into control, model,
      medication, acupuncture and moxibustion groups, with 20 rats in each group.
      Primary dysmenorrhea model was established by subcutaneous injection of
      Benzestrofol for 10 days and intraperitoneal injection of Oxytocin for 1 d. Rats
      of the medication group were fed with extractum leonuri inspissatum (8 g/100 g)
      and those of the moxibustion group treated with drug-paste separated moxibustion
      at "Mingmen" (GV 4). For rats of the acupuncture group, a filiform needle was
      inserted into GV 4, manipulated for a while and retained for 30 min. The
      treatment of the latter 3 groups was conducted once daily for 7 days. The rat's
      body-writhing latency and times during 30 min were recorded. The contents of
      serum E2 and P were detected by ELISA, and the expression of estrogen receptor
      (ER) mRNA and progesterone receptor (PR) mRNA in the endometrium was determined
      by quantitative real-time (RT)-PCR. RESULTS: (1) The body-writhing latency was
      shorter and the writhing times were more in the model group than in the control
      group (P < 0.01). Compared with the model group, the body-writhing latency was
      significantly increased and the writhing times were obviously decreased in the
      medication, acupuncture and moxibustion groups (P < 0.01). There were no
      significant differences among the medication, acupuncture and moxibustion groups
      in the body-writhing latency (P > 0.05), but the body-writhing numbers of the
      acupuncture and moxibustion groups were markedly lower than that of the
      medication group (P < 0.01). (2) Compared with the control group, serum E2
      content and endometrial ER mRNA expression level were significantly increased,
      and serum P content and endometrial PR mRNA level evidently decreased in the
      model group (P < 0.01, P < 0.05). In comparison with the model group, serum E2
      contents and endometrial ER mRNA expression levels were considerably down
      regulated, and serum P contents and endometrial PR mRNA expression levels
      markedly up-regulated in the medication, acupuncture and moxibustion groups (P <
      0.01, P < 0.05). The effects of the moxibustion group were significantly superior
      to those of the acupuncture and medication groups, and those of the acupuncture
      group were also significantly superior to those of the medication group in
      lowering E2 and endometrial ER mRNA levels, and raising serum P and endometrial
      PR mRNA expression levels (P < 0.01, P < 0.05). CONCLUSION: Drug-paste separated
      moxibustion of GV 4 is effective in relieving pain in primary dysmenorrheal rats,
      which is probably associated with its effects in down-regulating serum E2 content
      and endometrial ER mRNA expression, and up-regulating serum P and endometrial PR
      mRNA expression levels.

PMID- 24308181
TI  - [Effect of acupuncture intervention on hippocampal neuron loss and astrocytosis
      in SAMP 8 mice].
AB  - OBJECTIVE: To observe the effect of "Sanjiao Acupuncture Therapy" on hippocampal
      selective neuron loss and astrocytosis in senile accelerated mice (SAM) so as to
      reveal its mechanism underlying improvement of Alzheimer's disease (AD). METHODS:
      A total of 18 seven-month old male SAM prone 8 (SAMP 8) were selected and
      randomly allocated into model group, acupuncture group, and non-acupoint group.
      Moreover, 6 age- and sex-matched SAM resistant 1 (SAMR 1) were enrolled as the
      homology normal control group. For mice of the acupuncture group, "Sanjiao
      Acupuncture Therapy" [manual acupuncture stimulation of "Danzhong" (CV 17),
      "Zhongwan" (CV 12), "Qihai" (CV 6), "Zusanli" (ST 36) and "Xuehai"(SP 10)] was
      given, and for rats of the non-acupoint group, manual acupuncture stimulation was
      applied to bilateral costal region (non-acupoints, below the costal region and 10
      and 15 mm superior to the iliac crest). The treatment was conducted once daily
      for 14 days. At the end of each experiment, the mouse's hippocampus tissue was
      taken out after routine perfusion and fixing for paraffin sections which were
      stained by toluidine blue technique for observing changes of neurons and by
      immunohistochemistry for analyzing glial fibrillary acidic protein (GFAP)
      immunoactivity of astrocytes. RESULTS: Compared with the control group, a marked
      neuron loss was found in the model, acupuncture and non-acupoint groups (P <
      0.01). The numbers of neurons of hippocampal CA 1 and CA 3 regions in the
      acupuncture group were significantly more than those in the model group (P <
      0.05). Compared with the control group, the expression level of hippocampal GFAP
      was markedly increased in the model group (P < 0.01). In comparison with the
      control group, the average expression area, optical density values and the number
      of GFAP-labeled astocytes were significantly upregulated in the model group (P <
      0.01). While in comparison with the model group, these 3 indexes were apparently
      downregulated in the acupuncture group (P < 0.01) but not in the non-acupoint
      group except the average expression area, suggesting a reduction of hippocampal
      astrocyte activity after acupuncture intervention. A negative correlation was
      found between the expression level of GFAP and the number of astrocytes.
      CONCLUSION: "Sanjiao Acupuncture Therapy" can lower or delay neuron loss,
      suppress astrocytosis, and regulate the relationship between neuron and
      astrocyte, which may contribute to its function in relieving AD.

PMID- 24308182
TI  - [Effect of electroacupuncture intervention on blood-lipid, high-sensitivity C
      reactive protein and adiponectin levels in hyperlipidemia rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Zusanli" (ST 36) and "Zhongwan" (CV 12) on blood-lipid, high-sensitivity C
      reactive protein (HS-CRP) and adiponectin (ADPN) levels in hyperlipidemia rats,
      so as to study its mechanisms underlying improvement of hyperlipidemia. METHODS:
      Thirty-two male Wistar rats were randomly divided into control group, model
      group, manual acupuncture group and EA group (n = 8 in each group).
      Hyperlipedemia model was established by feeding the rats with high fat diet for
      40 days. Manual acupuncture and EA stimulation were separately applied to
      unilateral "Zusanli" (ST 36) and "Zhongwan" (CV 12),once daily for 4 weeks. Serum
      triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol
      (HDL-C), low density lipoprotein cholesterol (LDL-C) levels were determined by
      chromatometry, and serum HS-CRP and ADPN contents detected by immunity
      turbidimetric method and euzymelinked immunosorbent assay, respectively. RESULTS:
      Compared with the control group, serum TC, TG, LDL-C and HS-CRP levels were
      significantly upregulated in the model group (P < 0.05, P < 0.01), while serum
      HDL-C and ADPN levels remarkably reduced after modeling (P < 0.05, P < 0.01). In
      comparison with the model group, serum TC, TG, LDL-C and HS-CRP contents were
      considerably decreased in both manual acupuncture and EA groups (P < 0.05, P <
      0.01), and serum HDL-C and ADPN contents were evidently upregulated in the manual
      acupuncture and EA groups (P < 0.05, P < 0.01). The effect of EA in decreasing
      serum TC, TG, LDL-C and HS-CRP, and increasing serum ADPN was superior to that of
      manual acupuncture (P < 0.05). CONCLUSION: EA intervention has a remarkably
      positive effect on hyperlipidemia by reducing serum TC, TG, LDL-C and HS-CRP
      contents and upregulating serum HDL-C and ADPN levels in hyperlipidemic rats.

PMID- 24308183
TI  - [Effect of electroacupuncture intervention on expression of corticotropin
      releasing factor protein in hypothalamus and hippocampus of traumatized rats].
AB  - OBJECTIVE: To observe changes of anesthesia analepsia time and hypothalamic and
      hippocampal corticotropin-releasing factor (CRF) protein expression after
      electroacupuncture (EA) intervention in acute traumatic rats, in order to explore
      its mechanism underlying relief of post-operative stress. METHODS: Twenty male
      Sprague-Dawley rats were randomly divided into normal control group, model group,
      sham EA group and EA group (5 rats/group). Acute traumatic model was established
      by left lobectomy. For rats of the sham EA group, two filiform needles were
      inserted into the right "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) respectively,
      without needle-twirling and without electrical stimulation. For rats of the EA
      group, the right ST 36 and SP 6 were electrically stimulated at 2 Hz/100 Hz and 2
      mA for 30 minutes after needle insertion. Anesthesia analepsia time was recorded
      and righting reflex was tested for the acute traumatized rats. The expression of
      CRF protein in the hypothalamus and hippocampus was analyzed with Western blot.
      RESULTS: The anesthesia analepsia time and righting reflex recovery time were
      significantly shorter in the EA group than in the model group and sham EA group
      (P < 0.01). There was a close correlation between the anesthesia analepsia time
      and righting reflex recovery time (P < 0.05). In comparison with the normal
      group, the expression level of hippocampal CRF protein was significantly
      decreased whereas that of hypothalamic CRF protein evidently increased in the
      model group (P < 0.05). Compared with the model group, hippocampal CRF protein
      expression was considerably upregulated and hypothalamic CRF protein remarkably
      down-regulated in the EA group (P < 0.05). A markedly negative correlation was
      found between hypothalamic CRF and hippocampal CRF protein expression, and
      between hippocampal CRF expression and the stimulating mode (P < 0.001), and a
      positive correlation was found between hypothalamic CRF expression and righting
      reflex, and between hippocampal CRF expression and EA intervention (P < 0.01).
      CONCLUSION: EA intervention can shorten anesthesia analepsia time and righting
      reflex recovery time in liver-traumatized rats, which is closely associated with
      its effects in upregulating hippocampal CRF protein expression and down
      regulating hypothalamic CRF expression. It suggests that CRF mediated hippocampus
      hypothalamus-pituitary-axis is involved in EA induced reduction of post-surgical
      stress.

PMID- 24308184
TI  - [Segmental and regional distribution of neurons and their axonal projection
      associated with acupoint "yongquan" (KI 1) in the rat: cholera toxin subunit B
      method].
AB  - OBJECTIVE: To observe the distribution of neurons and their axonal projection
      associated with "Yongquan" (KI 1) area by neural tracing technique with cholera
      toxin subunit B (CTB). METHODS: A total of 5 microL of 1% CTB solution was
      injected into the front central part of hind foot plantar (corresponding to the
      KI 1 region in the human body) using a Hamilton microsyringe. After 3 survival
      days, the rats were deeply anesthetized and transcardically perfused for
      collecting the dorsal root ganglia (DRGs), spinal cord and brain tissues.
      Following fixing in 4% paraforldehyde containing phosphate buffer solution (PBS)
      and incubation in PBS containing 25% glucose solution, the aforementioned tissues
      were sectioned to be stained with immunofluorescence or immunohistochemistry for
      revealing the labeled sensory neurons and their tansganglionic projection and
      motor neurons. RESULTS: All the labeled neurons (sensory and motor neurons) and
      transganglionic axonal projection appeared ipsilaterally to the injection side.
      The labeled sensory neurons were located in the DRGs of lumbar 3-5 segments (L 3
      L 5) with a higher concentration at L 4, while motor neurons distributed in the
      dorsolateral portion of spinal ventral horn from L 3 to L 6 with a higher
      concentration at L 5. In addition, transganglionic axonal projections were found
      to situate in the medial part of laminae III - IV from L 3 to L 5, as far as in
      the gracile nucleus. CONCLUSION: Acupoint KI 1 area is innervated by sensory
      neurons in L 3-L 5 DRGs and motor neurons from the dorsolateral ventral horns of
      L 3-L 6. The axonal projection of the primary sensory neurons distributes in the
      medial part of laminae III - IV of L 3-L 5 and gracile nucleus, respectively.

PMID- 24308185
TI  - [Effect of electroacupuncture intervention on N-methyl-D-aspartic acid receptor
      expression in spinal cord in rats with chronic constrictive injury of the sciatic
      nerve].
AB  - OBJECTIVE; To observe the changes of N-methyl-D-aspartic acid (NMDA) receptor
      expression of spinal cord after electroacupuncture (EA) intervention in rats with
      chronic constrictive injury (CCI) of the sciatic nerve so as to reveal the
      mechanism underlying improvement of neuropathic pain. METHODS: Sixty male SD rats
      were randomly divided into sham operation (sham) group, CCI model group and EA
      group (n = 20). CCI model was established by ligature of the right sciatic nerve
      with a piece of surgical chromic suture. For rats of the sham group, the right
      sciatic nerve was just isolated without ligature. The rats of the EA group were
      given with EA stimulation of "Weizhong" (BL 40) and "Huantiao" (GB 30) on the
      injured side at a frequency of 2 Hz, electric current of 1-3 mA for 30 min
      (increasing 1 mA every 10 min). The treatment was conducted once a day from the
      11th day to the 20th day after modeling. NMDA receptor 2 B subunit (NR 2 B)
      protein and mRNA expression levels in the spinal cord were determined by
      immunohistochemistry, Western blot and reverse transcription (RT)-polymerase
      chain reaction (PCR), respectively, and spinal NMDA receptor subunit 1 (NR 1)
      protein and mRNA expression levels were measured by Western blot and RT-PCR,
      respectively. RESULTS: In comparison with the sham group, NR 1 protein and mRNA
      expression levels of the model group in the spinal cord were considerably
      upregulated after CCI (P < 0.01, P < 0.05). In comparison with the model group NR
      1 protein and mRNA expression levels of the EA group in the spinal cord were
      evidently down-regulated (P < 0.05). No significant changes of NR 2 B protein and
      mRNA expression after CCI and EA stimulation were found after
      immunohistochemistry, Western blot and RT-PCR measurements (P > 0.05).
      CONCLUSION: EA intervention is effective in alleviating neuropathic pain in CCI
      rats, which may be closely related to its effects in lowering functional activity
      of NR 1 protein and mRNA in the spinal cord.

PMID- 24308186
TI  - [Effect of electroacupuncture intervention at different time-points in a day on
      expression of c-fos and neuronal nitric oxide synthase in medial prefrontal
      cortex in ketamine addiction rats].
AB  - To observe the effects of electroacupuncture(EA) stimulation of "Zusanli"(ST 36)
      and "Sanyinjiao"(SP 6) at different time-points of a day on the expression of c
      fos and neuronal nitric oxide synthase (nNOS) in the medial prefrontal cortex
      (mPFC) in rats with ketamine addiction. METHODS: A total of 56 SD rats were
      randomized into control group, saline group, model group and EA group. The EA
      group was further divided into Zi-shi (23 : 00), Mao-shi (05 : 00), Wu-shi (11 :
      00) and You-shi (17 : 00) subgroups (n = 8 in each group or subgroup). Ketamine
      addiction model was established by intraperitoneal administration of ketamine
      (100 mg/kg), once a day for 7 days. EA (2 Hz, 3 V) was applied to unilateral
      "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) acupoints for 30 min, once daily for 7
      days. The expression of c-fos and nNOS in the mPFC was detected by
      immunohistochemistry. RESULTS: Following EA intervention for 7 days, the animals'
      daily life activities including body stretching, standing, jumping, circling,
      falling on the back and fur-licking in the EA group (Wu-shi and You-shi
      subgroups) were close to those of the normal control and saline groups, being
      much better than the model group. Compared with the normal control group and
      saline group, the expression levels of c-fos and nNOS in the mPFC in the model
      group were significantly upregulated (P < 0.05). Compared with the model group,
      the expression levels of both c-fos and nNOS were considerably down-regulated in
      the Wu-shi (11 : 00) and You-shi (17 : 00) subgroups (P < 0.05), rather than in
      the Zi-shi (23 : 00) and Mao-shi (05 : 00) subgroups (P > 0.05). CONCLUSION: EA
      of ST 36 and SP 6 at 11 : 00 and 17 : 00 can decrease the expression o fc-fos and
      nNOS in the mPFC in ketamine addiction rats, which may contribute to its effects
      in improving the rats' behavior activity.

PMID- 24308187
TI  - [Cumulative analgesic effects of EA stimulation of sanyinjiao (SP 6) in primary
      dysmenorrhea patients: a multicenter randomized controlled clinical trial].
AB  - OBJECTIVE: To compare the cumulative analgesic effect of electroacupuncture (EA)
      stimulation of Sanyinjiao (SP 6), Xuanzhong (GB 39) and non-acupoint for primary
      dysmenorrhea patients. METHODS: A total of 200 patients with primary dysmenorrhea
      were randomly assigned to Sanyinjiao (SP 6, a dysmenorrheal-relieving related
      acupoint) group, Xuanzhong (GB 39, an unrelated acupoint) group, non-acupoint
      group and control group, with 50 cases in each group. The participants were
      administered with EA (2 Hz/100 Hz, 0.5-1.6 mA) at SP 6, GB 39 and non-acupoint
      for 30 min, once daily for 3 consecutive days. The intensity of the pain was
      ranked from 0 (no pain) to 100 (intolerable) using visual analogue scale (VAS)
      and RSS (Cox retrospective symptom scale) severity rating scores (RSS-COX 2)
      before and after three interventions. RESULTS: In comparison with the control
      group, VAS and RSS-COX 2 scores were significantly lower in the SP 36, GB 39 and
      non-acupoint groups (P < 0.001, P < 0.05), suggesting an alleviation of the pain
      severity after EA treatment. No significant differences were found among the
      three treatment groups in both VAS and RSS-COX 2 scores (P > 0.05). CONCLUSION:
      EA stimulation of SP 6, GB 39 and non-acupoint has a good cumulative analgesic
      effect in patients with primary dysmenorrhea.

PMID- 24308188
TI  - [Observation on clinical effect of ZHUANG medicine mediated thread moxibustion
      combined with medication for patients with ulcerative colitis].
AB  - OBJECTIVE: To observe the clinical effect and safety of Sulfasalazine (SASP)
      combined with ZHUANG medicine mediated thread moxibustion (ZMMTM) for patients
      with mild and moderate ulcerative colitis (UC). METHODS: A total of 46 UC
      patients were randomly and equally divided into moxibustion group (SASP combined
      with ZMMTM) and SASP medication group. Patients of both groups were treated by
      oral administration of SASP (1 g, tid) for six weeks. For patients of the
      moxibustion group, ZMMTM was applied to points Tianshu (ST 25), Qihai (CV 6),
      Guanyuan (CV 4), and Dachangshu (BL 25), once a day, for 20 times. The
      therapeutic effect was assessed according to Schroeder and colleagues' method
      (1987), scores of Baron' s endoscope scale (0 - 9 scoring standards, 1964), 0 - 3
      scoring standards of activity indexes (including 4 items of diarrhea, hemorrhage,
      mucosal appearance and doctors' evaluation), respectively. RESULTS: Of the two 32
      UC patients in the medication and moxibustion groups, 6 and 9 had a complete
      remission in their symptoms, 6 and 7 experienced a remarkable improvement, 5 and
      6 were effective, and 6 and 1 was invalid, with the effective rates being 73.91%
      and 95.65%, respectively. Following the treatment, both endoscopic score and
      activity index in the moxibustion group were significantly lower than those of
      the medication group (P < 0.05). CONCLUSION: ZMMTM combined with medication is
      significantly superior to simple medication in relieving clinical symptoms of
      mild and moderate UC patients.

PMID- 24308189
TI  - [Clinical trials of acupuncture intervention combined with sitting training for
      cerebral palsy children with parafunctional sitting position].
AB  - OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) combined
      with sitting training for cerebral palsy (CP) children with parafunctional
      sitting position. METHODS: A total of 120 parafunctional sitting CP child
      patients were randomly and equally divided into sitting training (control) group
      and EA plus sitting training (EA) group. The sitting training included assistant
      sitting, legs-crossing-sitting, sitting with one-leg extending, long-term
      sitting, balancing-sitting, chair-climbing, and pron and hand-supporting, twice
      daily. EA (4 Hz, a tolerable strength) was applied to Mingmen (GV 4), Jizhong (GV
      6), Shenshu (BL 23), and Pishu (BL 20) for 30 min, once daily. Both sitting
      training and EA treatment were conducted 5 times a week and continuously for a
      month. Twenty-items of sitting functions (0 - 3 point scaling) of Gross Motor
      Function Measure (GMFM) were used to evaluate the infantile patients' motor
      function and Nimodipine-method was employed to assess the curative effect.
      RESULTS: The sitting function scores were significantly increased in both control
      and EA groups compared with pre-treatment in the same one group (P < 0.01), and
      were apparently higher in the EA group than in the control group (P < 0.05),
      suggesting a better therapeutic effect of EA plus sitting training. EA plus
      sitting training intervention was better for the spastic and hypotonic patterns
      of CP patients than the other patterns in the therapeutic effect (P < 0.01). Of
      the two 60 cases of CP children in the control and EA groups, 20 (33.33%) and 22
      (36.67%) experienced marked improvement, 24 (40.00%) and 30 (50.00%) were
      effective, and 16 (26.67%) and 8 (13.33%) failed, with the effective rates being
      73.33% and 86.67% respectively. CONCLUSION: Acupuncture intervention combined
      with sitting training is better than sitting training intervention alone in
      improving cerebral palsy children with parafunctional sitting position,
      especially for the spastic and hypotonic CP patients.

PMID- 24308190
TI  - [Observation on therapeutic effect of acupuncture intervention combined with
      hyperbaric oxygen therapy for delayed encephalopathy caused by carbon monoxide
      poisoning].
AB  - OBJECTIVE: To observe the curative effect of acupuncture intervention combined
      with hyperbaric oxygen chamber treatment for delayed encephalopathy in 32 carbon
      monoxide (CO) poisoning patients. METHODS: A total of 62 CO poisoning
      encephalopathy patients were randomized into control group (n = 30) and
      acupuncture group (n = 32). Patients of the two groups were all treated with
      medicines (energy mixture solution, hormones, brain cell activators, calcium ion
      blockers, anti-inflammatory agents, etc.) and hyperbaric oxygen treatment (oxygen
      inhaling for 90 min/time). Moreover, patients of the acupuncture group received
      acupuncture stimulation of bilateral Taixi (KI 3), Xuanzhong (GB 39), Hegu (LI
      4), Taichong (LR 3), and Fengchi (GB 20). All the treatments were conducted once
      daily for 30 days. The therapeutic effect of the treatments for neurological
      function was assessed by NIH Stroke Scale (NIHSS, 34 points in total; including
      15 items as consciousness, horizontal eye movement, visual power, visual field,
      facial muscular motion, limb movement, coordination movement, sensory and
      language levels, etc.). RESULTS: After the treatment, of the 30 and 32 cases in
      the control and acupuncture groups, 1 and 4 were cured, 3 and 8 experienced
      marked improvement, 4 and 11 were improved, and 22 and 9 invalid, with the
      effective rates being 26.1% and 72.3%, respectively. The therapeutic effect of
      the acupuncture group was significantly superior to that of the control group (P
      < 0.05). The average NIHSS score was 5.01 +/- 0.72 in the acupuncture group,
      being significantly lower than that (8.30 +/- 0.45) in the control group (P <
      0.05). CONCLUSION: Acupuncture treatment can effectively strengthen the efficacy
      of hyperbaric oxygen therapy in the treatment of delayed encephalopathy caused by
      carbon monoxide poisoning.

PMID- 24308191
TI  - [Effect of cervical paravertebral block combined with acupuncture intervention on
      cervicogenic headache].
AB  - OBJECTIVE: To observe the therapeutic effect of cervical paravertebral block plus
      acupuncture treatment for cervicogenic headache. METHODS: Sixty cases of
      cervicogenic headache were randomly and equally divided into cervical
      paravertebral block (control) group and acupuncture plus cervical paravertebral
      block (acupuncture) group. Paravertebral block was performed by injection of 5 mL
      of 0.3% lidocaine solution containing triamcinolone (10 mg) into the 2nd cervical
      paravertebral tissue from the cross point between the posterior border of the
      sternomastoid muscle and the angle of jaw, once every week for three weeks.
      Manual acupuncture stimulation was applied to Baihui (GV 20), unilateral Fengchi
      (GB 20) and Jiaosun (SJ 20), once daily for 3 weeks. The patients' headache
      severity was assessed by visual analogue scale (VAS) and their cervical vertebral
      activity assessed by range of motion (ROM) before and after the treatment.
      RESULTS: Compared with pre-treatment in the same one group, the scores of both
      VAS and ROM at time points of one, two and three weeks after the treatment were
      significantly decreased in the control and acupuncture groups (P < 0.05),
      suggesting a marked improvement of both headache and cervical motion after the
      treatment. Comparison between the two groups showed that the VAS and ROM scores
      of the acupuncture group were evidently lower than those of the control group at
      each time point after the treatment (P < 0.05), displaying a better therapeutic
      effect of acupuncture plus paravertebral block for cervicogenic headache.
      CONCLUSION: Acupuncture combined with cervical paravertebral block is effective
      in relieving cervicogenic headache and improving cervical vertebral activity in
      cervicogenic headache patients, and can strengthen the therapeutic effect of
      simple paravertebral block.

PMID- 24308192
TI  - [Research on action features of acupuncturist experts' acupuncture needle
      twirling skills].
AB  - OBJECTIVE: To observe the features of acupuncture needle twirling manipulations
      in order to promote the development of objective and quantitative performance
      standards of acupuncture manipulation. METHODS: Twelve expert acupuncturists and
      12 novices were enrolled in this study. Everyone of them was instructed to
      perform 10 trials of the uniform reinforcing and reducing technique of
      acupuncture on an artificial skin-pad that was mounted to a six-axis force
      transducer and each subject had his or her dominant hand index finger affixed
      with an infrared light emitting diode for acquiring parameters of acupuncture
      needle manipulation. The force transducer was used to measure the force the
      participant applied as they held an acupuncture needle to stimulate the skin-pad,
      and at the mean time, an optoelectric camera was employed to measure the position
      of the diode. RESULTS: In comparison with the expert acupuncturist group, the
      straggling coefficient of needle-twirling frequency was significantly bigger in
      the novice group (P < 0.01), suggesting a higher consistency in the trial-by
      trial needle-twirling operation of the expert acupuncturists. Comparison of the
      needle-twirling force showed that the force values of the Z-axis in both expert
      group and novice group were considerably higher than those of the X-axis and Y
      axis in the same one group (P < 0.01). The time of pre-needle-twirling of the
      novice group was markedly longer than that of the expert group (P < 0.01),
      suggesting a skilled operation technique of the expert acupuncturists. No
      significant differences were found between the expert acupuncturist group and
      novice group in the needle-twirling amplitude, frequency, force and total
      operation time (P > 0.05). CONCLUSION: Movement frequency consistency and
      temporal efficiency are the action features of expert acupuncturists in
      performing the uniform reducing-reinforcing twirling skill, which differentiates
      the performances of experts from novices. The assessment and training of this
      acupuncture skill should focus on these kinematic features.

PMID- 24308193
TI  - [Application of red-hot needle therapy to management of neurological dysfunction
      related diseases revealed by data mining technology].
AB  - OBJECTIVE: To analyze the application rules of the red-hot needle therapy to the
      treatment of neurological dysfunction related diseases in the ancient and modern
      clinical practice by data mining. METHODS: Modern literature data about the red
      hot needle therapy in medical journals and partial medical books were collected
      to establish a "red-hot needling literature network database", followed by
      manually selecting its applicable illness spectrum of neurological dysfunction.
      Then, the application rules of the red-hot needling for neurological dysfunction
      related diseases, including selection of acupuncture needle types, acupoints,
      operation methods, etc. were analyzed. RESULTS: A total of 17 categories of
      neurological dysfunction related diseases treated by red-hot needle therapy were
      collected from medical journals, ten categories of diseases collected from
      medical cases, and five categories of diseases collected from medical books. The
      most frequently seen diseases were herpes zoster/residual neuralgia of herpes
      zoster, facial paralysis, facial neuritis (prosopodynia), and stroke/stroke
      sequelae, etc. During acupuncture treatment, doctors (acupuncturists) usually
      selected Ashi points, performed spot pricking or quick insertion and withdrawal
      of the red-hot needle, or adopted additional surrounded needling around the focus
      of infection according to syndrome differentiation in some cases. CONCLUSION: Red
      hot needle therapy has a good curative efficacy in relieving symptoms of
      neurological dysfunction related diseases, being worthy of promotion in clinical
      practice.

PMID- 24308194
TI  - [Comments on influence of different functional status of the body on clinical
      effects of acupuncture therapy].
AB  - Functional status is an important factor affecting clinical therapeutic effect of
      acupuncture therapy. Authors of the present article make an analysis on the
      related descriptions of ancient classical books about the patient's body
      constitution, age, duration of disease, type of disease or clinical conditions,
      psychological state, etc. which determine the functional state of patients.
      Moreover, the authors also make some comments on the results of modern clinical
      trials and experimental studies. However, till now, the results of many related
      modern studies were lower in reliability due to unreliable methodology. Fewer
      clinical trials involve the patient's psychological state, and constitution from
      the viewpoint of Chinese medicine. Correspondingly, the related experimental
      studies are fewer. The authors suggest that in the coming days clinical trials
      should be greatly improved in quality and the mutual interference among the
      influential factors should be excluded. At the same time, experimental studies on
      the related biochemical mechanisms should be strengthened.

PMID- 24308195
TI  - Alternative representation for the stability diagram of quadrupole ion traps upon
      additional quadrupolar excitation.
AB  - We present a combined theoretical and experimental study of the stability of ions
      in a linear ion trap under the application of one or two auxiliary radiofrequency
      (RF) fields, in order to perform simultaneous resonant excitation/ejection of
      several different ions. The influence of the amplitude and frequency of the
      auxiliary field is addressed through the construction of experimental and
      theoretical stability diagrams. Theoretical diagrams are constructed using the
      method developed by Konenkov et al. [J. Am. Soc. Mass Spectrom. 13, 597 (2002)].
      We propose a new representation of stability diagrams more adapted to the study
      of auxiliary excitations than the canonical one. Stability regions are
      represented as a function of the fundamental RF amplitude and of the relative
      intensity of the excitation. This representation facilitates the monitoring of
      the evolution of the mass-selectivity of first- and higher-order resonant
      excitations in the trap, for which an empirical law is derived. We also show that
      the relative phase shift between the excitation field and the main driving field
      has a strong influence on the shape of the diagrams.

PMID- 24308196
TI  - Specific enrichment and direct detection of phosphopeptides on insoluble
      transition metal oxide particles in matrix-assisted laser desorption/ionization
      mass spectrometry applications.
AB  - Several transition metal oxides, such as iron (III), nickel (II) and zirconium
      (IV) oxides, were examined in detail for the specific enrichment and the
      purification of phosphopeptides from a digested peptide mixture solution.
      Phosphopeptide enrichment was performed on the metal oxide particles using a
      peptide mixture obtained bytryptic digestion of beta-casein. The mixture of
      protein digests containing bovine serum albumin (BSA): beta-casein digests (100:1
      mole ratio) was also used for the phosphopeptide enrichment. Furthermore, non-fat
      milk digest was examined as a complex biological sample. In each phosphopeptide
      enrichment process, phosphopeptides were specifically enriched and separated from
      the non-phosphopeptides. The phosphopeptides were adsorbed onto the metal oxide
      surface at acidic pH values between 1.0 and 2.0 and, for desorption of
      phosphopeptides from metal oxide particles, pH values were examined and optimized
      in the enrichment studies. The analysis of phosphopeptides were carried out by
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) using
      2,5-dihydroxybenzoic acid matrix containing 1.0% phosphoric acid to obtain
      intense protonated signals and to overcome degradation of the phosphopeptides by
      phosphate group loss in mass spectrometric conditions. Moreover, it was
      demonstrated that the direct detection of phosphopeptides from the surface of the
      metal oxide particles was possible using MALDI-MS by mixing the phosphopeptide
      adsorbed metal oxide particles with MALDI matrix solution in slurry form before
      the analysis. Thus, the effects of interferences arising from chemical species
      used in the desorption process was successfully eliminated for the fast and
      sensitive detection of phosphopeptides in MALDI-MS applications.

PMID- 24308197
TI  - Characterization of low-molecular weight iodine-terminated polyethylenes by gas
      chromatography/mass spectrometry and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry with the use of derivatization.
AB  - Gas chromatography/mass spectrometry (GC/MS) and matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry, in
      conjunction with various derivatization approaches, have been applied to
      structure determination of individual oligomers and molecular-mass distributions
      (MMD) in low-molecular mass polyethylene having an iodine terminus. Direct GC/MS
      analysis has shown that the samples under investigation composed of polyethyelene
      iodides (major components) and n-alkanes. Exchange reaction with methanol in the
      presence of NaOH gave rise to methoxy-derivatives and n-alkenes. Electron
      ionization mass spectra have shown that the former contained terminal methoxy
      groups indicating the terminal position of the iodine atom in the initial
      oligomers. MMD parameters have been determined with the aid of MALDI mass
      spectrometry followed by preliminary derivatization-formation of covalently
      bonded charge through the reaction of iodides with triphenylphosphine,
      trialkylamines, pyridine or quinoline. The mass spectra revealed well-resolved
      peaks for cationic parts of derivatized oligomers allowing the determination of
      MMD. The latter values have been compared with those calculated from GC/MS data.

PMID- 24308198
TI  - Detection of nerve agents using proton transfer reaction mass spectrometry with
      ammonia as reagent gas.
AB  - The chemical warfare agents (CWA) Sarin, Soman, Cyclosarin and Tabun were
      characterised by proton transfer mass spectrometry (PTRMS). It was found that
      PTRMS is a suitable technique to detect nerve agents highly sensitively, highly
      selectively and in near real-time. Methods were found to suppress molecule
      fragmentation which is significant under PTRMS hollow cathode ionisation
      conditions. In this context, the drift voltage (as one of the most important
      system parameters) was varied and ammonia was introduced as an additional
      chemical reagent gas. Auxiliary chemicals such as ammonia affect ionisation
      processes and are quite common in context with detectors for CWAs based on ion
      mobility spectrometry (IMS). With both, variation of drift voltage and ammonia as
      the reagent gas, fragmentation can be suppressed effectively. Suppression of
      fragmentation is crucial particularly concerning the implementation of an
      algorithm for automated agent identification in field applications. On the other
      hand, appearance of particular fragments might deliver additional information.
      Degradation and rearrangement products of nerve agents are not distinctive for
      the particular agent but for the chemical class they belong to. It was found that
      switching between ammonia doped and ordinary water ionisation chemistry can
      easily be performed within a few seconds. Making use of this effect it is
      possible to switch between fragment and molecular ion peak spectra. Thus,
      targeted fragmentation can be used to confirm identification based only on single
      peak detection. PTRMS turned out to be a promising technique for future CWA
      detectors. In terms of sensitivity, response time and selectivity (or confidence
      of identification, respectively) PTRMS performs as a bridging technique between
      IMS and GC-MS.

PMID- 24308199
TI  - Identification of wood between Phoebe zhennan and Machilus pingii using the gas
      chromatography-mass spectrometry direct injection technique.
AB  - In this paper, the technique of direct injection gas chromatography-mass
      spectrometer (GC-MS) was employed to discriminate between two batches of wood
      (Phoebe zhennan and Machilus pingii) with characteristic smells. Based on the GC
      MS fingerprints obtained, similarities between samples were evaluated via
      correlation coefficient, hierarchical clustering and characteristic constituents
      analysis. The results showed that distinct differences in total ion chromatograms
      existed between the two species of wood and their correlation coefficients were
      low; however, the relationship between the same species of different batches
      showed the opposite; meanwhile, the analysis of hierarchical clustering and
      characteristic constituents also demonstrated an interrelationship. All the
      analytical methods achieved the goal of identification between the two species of
      wood, which verified that the technique can be used to identify different species
      of wood with characteristic smells.

PMID- 24308200
TI  - Characterization of secondary metabolites from the raphides of calcium oxalate
      contained in three araceae family plants using laser microdissection and ultra
      high performance liquid chromatography-quadrupole/time of flight-mass
      spectrometry.
AB  - The dried stem tubers of Pinellia ternata (Thunb.) Breit, P. pedatisecta Schott
      and Typhonium flagelliforme (Lodd.) Blume from the Araceae family are used as
      Chinese medicines, namely Banxia, Zhangye Banxia and Shui Banxia, respectively.
      They have been reported to have a strong irritative effect on mucosa. Previous
      studies have indicated that the pure raphides of calcium oxalate contained in the
      stem tubers of three plants have attributed to this strong irritation. However,
      the processed products of the stem tubers of P. ternata, including Fabanxia,
      Qingbanxia and Jiangbanxia, have been found to have no irritative effects on
      mucosa. Currently, the secondary metabolites from the raphides of calcium oxalate
      contained in the stem tubers of P. ternata with its processed products, P.
      pedatisecta and T. flagelliforme were analyzed by means of laser microdissection
      and ultra-high performance liquid chromatography-quadrupole/ time of flight-mass
      spectrometry. The results indicate that the stem tubers of P. ternata P.
      pedatisecta and T. flagelliforme mainly contain amino acids, fatty acids, cyclic
      dipeptides and alkaloids. The secondary metabolite profile of the stem tuber of
      P. ternata was different from those of its processed products, Fabanxia,
      Qingbanxia and Jiangbanxia. However, the secondary metabolites from their
      raphides of calcium oxalate all contained beta-sitosterol, sitosterol palmitate,
      trigonelline, octadecenoic acid, pedatisectine A and thymidine. The raphides of
      calcium oxalate from P. ternata, P. pedatisecta and T. flagelliforme do not
      include any specific irritants. The results indicated that the irritation induced
      by raphides of calcium oxalate of three Araceae family plants is not relevant to
      the secondary metabolites but relates to the special needle shape.

PMID- 24308201
TI  - A preliminary investigation on placenta protein profile reveals only modest
      changes in well controlled gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) is associated with a wide range of tissue
      specific changes depending on the quality of glycemic control of the mothers.
      Here we tested the hypothesis that GDM is associated with alterations in the
      human term placenta proteome. For this aim, two different approacheswere
      employed. The placenta homogenates from 20 healthy subjects and those from 20 GDM
      pregnant women were pooled. The two samples thus obtained were analyzed by matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS) and the
      proteins detected were tentatively identified by comparison of their molecular
      weight with the Human Protein Reference Database, restricting the search to the
      species expressed in the placenta tissue. However this approach led to misleading
      results: in fact, an in deep analysis of the spectra and tandem mass spectrometry
      (MS/MS) measurements of the digestion products from the protein detected,
      unequivocally proved that the species observed are maternal and fetal globins.
      Consequently, the two pools were analyzed by 1D sodium dodecyl sulphate
      polyacrylamide gel electrophoresis; the different bands obtained were digested by
      trypsin and the digestion products were analyzed by MALDI-MS; the protein
      identification was carried out by comparison of the peptide mass fingerprint with
      databases. Only modest quantitative differences were observed between the
      placenta protein profiles of healthy and GDM subjects, indicating that GDM, if
      well controlled, induces only minor changes in the placental proteome. One
      example of differently expressed proteins in the placenta homogenate pool from
      GDM and the controls was the SRRM1 protein, a member of the serine-arginine
      protein kinase family; for GDM samples, the MALDI spectrum of its digestion
      products showed the presence of molecular species attributable to glycation and
      glyco-oxidation processes.

PMID- 24308202
TI  - Croatian anthropological terminology--challenges and dilemmas.
AB  - This paper describes the project ANTRONA aimed at constructing basic
      anthropological terminology that covers the entire range of anthropology as a
      science. It is a part of national language planning oriented terminology
      management for the Croatian language, and as such it is focused solely at the
      production of a terminographic database. The major difficulties encountered
      during the procedural stages of the project are outlined, such as the wide range
      of the interdisciplinary field of anthropology, including concepts and terms from
      natural and social sciences and humanities, as well as polysemy and fuzzy
      boundaries between the lexicon of the general language and specialized language.
      On the basis of several examples, we argue that terminography should be dealt
      with primarily by keeping in mind the range of its subsequent applications the
      aim of which is not only ontological, but also communicative in nature, and that
      functional pragmatic approach offers a more flexible framework for dealing with
      the demands of terminology in such an interdisciplinary field.

PMID- 24308203
TI  - The Croatian national termbank Struna: a new platform for terminological work.
AB  - The development of the Croatian Special Field Terminology program (known by its
      Croatian acronym Struna) began in 2007 as part of an initial coordination project
      launched at the initiative of the Croatian Standard Language Council, and has
      since been financed by the Croatian Science Foundation. It is being carried out
      at the Institute of Croatian Language and Linguistics, which serves as the
      national coordinator. This paper describes the current design of the e-Struna
      termbank and explains the adjustments made in the database structure and in the
      terminographic approach, both to support and reflect the methodological issues
      concerning interdisciplinary and multidisciplinary work. Based on examples taken
      from the Croatian anthropological terminology collection special attention is
      given to two frequently neglected categories of terminological description:
      context and note.

PMID- 24308204
TI  - Ethics of the profession of public relations--does the public relations affects
      on journalism in Croatia?
AB  - The UK's leading professional body for public relations "Chartered Institute of
      Public Relations" (CIPR) said that the public relations is about reputation--they
      are the result of what you do, what you say and what others say about you.
      Furthermore CIPR says that public relations are discipline whose objectives are
      safeguarding reputation, establishing understanding and pot pores, and the impact
      on the thinking and behavior of the public. Although the primary goal of public
      relations is to preserve and build a reputation, to tell the truth to a customer
      who has hired experts in this area, it seems that in its own way of development,
      public relations practitioners have stopped worrying about their reputation and
      the perception of the discipline within the public they address. All relevant
      professional bodies for public relations, including the Croatian Association for
      Public Relation (HUOJ), had set up codes of ethics and high standards according
      which the members and practitioners should be evaluated. Among other things stays
      that practitioner of public relations is required to check the reliability and
      accuracy of the data prior to their distribution and nurture honesty and
      accountability to the public interest. It seems that right this instruction of
      code of ethics has been often violated. In a public speech in Croatia, and
      therefore in the media, exist manipulation, propaganda, and all the techniques of
      spin, which practitioners of public relations are skillfully using in the daily
      transfer of information to the users and target groups. The aim of this paper is
      to determine what is the perception of the profession to the public. As in
      today's journalism increasingly present plume of public relations, we wish to
      comment on the part where journalism ends and begins PR and vice versa. In this
      paper, we analyze and compare codes of ethics ethics associations for public
      relations, as well as codes of ethics journalists' associations, in order to
      answer the question of where the boundaries of public relations and journalism
      are. Where one ends and the other begins, and the extent to which these two
      professions touch and affect each other. Is manipulation and spin present in the
      media, that is the questions that we seek the answer in this paper.

PMID- 24308205
TI  - The opinions of Polish nurses and patients on nursing protests.
AB  - The aim of this study is to explore nurses' and patients' opinions about nurses
      in Poland going on strike. The study was carried out in Poland between January
      and June 2009, using 150 nurses and 150 hospitalized patients. The study was
      conducted using two questionnaire surveys. The main reasons why nursing strikes
      are organized, in the opinions of nurses, are: higher wages, the improvement of
      working conditions and the improvement of the image of the nursing profession.
      The main reasons why nursing strikes are organized, in the opinions of patients,
      are: higher wages, not abiding standards of employment by government and the
      improvement of the image of the nursing profession. The main reasons for a lack
      of active participation in strikes are holidays and occupational and economic
      matters. Patients and nurses support nursing strikes. Both nurses (53.3%) and
      patients (42%) said that organizing nursing strikes is right and might improve
      the occupational situation of nurses.

PMID- 24308206
TI  - WHOQOL-bREF questionnaire as a measure of quality of life in sarcoidosis.
AB  - The aim of this study was to evaluate the usefulness of a short form of the
      WHOQOL questionnaire, the WHOQOL-BREF, which consists of 24 questions, in
      evaluating quality of life (QOL) in sarcoidosis patients. A group of 97
      sarcoidosis patients and a matched group of 97 healthy controls took part in the
      study. Their QOL was examined by means of the WHOQOL-BREF, and the respiratory
      functions were measured in sarcoidosis patients. The WHOQOL-BREF revealed
      significantly poorer QOL of sarcoidosis patients in the domains of Physical and
      Psychological Health in comparison to healthy controls. In contrast, sarcoidosis
      patients perceived their QOL significantly better than healthy controls in the
      domains of Social Relations and Environment. Differences between sarcoidosis
      patients and healthy controls were found in several items from the WHOQOL-BREF
      and some of them were modified by gender. However, the WHOQOL-BREF did not prove
      to be a sensitive measure of fatigue, which is the most common symptom in
      sarcoidosis patients.

PMID- 24308207
TI  - Analysis of self-determined motivation in basketball players through goal
      orientations.
AB  - The purpose of this study was twofold. Firstly to examine the relations between
      the different constructs that defines Nicholls' Achievement Goal Theory and Deci
      and Ryan's self-determination theory. Secondly to analyse the differences that
      exist between them with respect to the socio-demographic variables gender and
      age. A sample of 292 federated basketball players from the Region of Murcia
      (Spain) with ages between 14 and 18 years old was used. In addition, Castilian
      versions of The Perception of Success Questionnaire (POSQ) and the Sports
      Motivational Scale (SMS) were administered. Three statistical analyses were
      employed, a descriptive analysis, a correlation analysis and a regression
      analysis. The results showed a positive relation between ego orientation,
      extrinsic motivation and amotivation. The motivational relations between both
      theories and the differences with respect to gender and age are discussed. We
      have found out that mainly gender and also age differences are strong predictors
      of ego orientation, extrinsic motivation of external regulation and amotivation.
      We can also confirm that extrinsic motivation of external regulation positively
      predicts ego orientation and a decrease of task orientation. The results ratify
      the use of the Spanish version of the SMS to measure different types of
      motivation within the sports context.

PMID- 24308208
TI  - Treatment seeking behaviour in hypertension: factors associated with awareness
      and medication among socioeconomically disadvantaged migrants in Delhi, India.
AB  - The present study is apart of a cross-sectional prevalence study. Descriptive
      statistics were used to present the awareness, treatment and control of
      hypertension. Multiple logistic regression analyses were performed to examine the
      influence of socio-demographic and other variables on awareness and on current
      medication use. The results reveal that only 41% of the total hypertensive
      persons were aware of their hypertension status, and only 59% of them were on
      medication. Of those treated, only 5% had controlled hypertension. Multiple
      logistic regression analyses reveal that gender, age, pulse rate and education
      were significantly associated with awareness of hypertension whereas age is the
      only significant factor associated with medication use. The Hosmer and Lemeshow
      tests for goodness of fit reveal that these regression models are a good fit. The
      study concludes that undiagnosed hypertension is considerable. Awareness,
      treatment and control of hypertension are not adequate among socioeconomically
      disadvantaged migrants. Since hypertension has become a common problem, the
      health education and awareness campaigns along with facilities such as blood
      pressure screening and hypertension treatment through primary health care system
      are essential.

PMID- 24308209
TI  - Oculocutaneous albinism and consanguineous marriage among Spanish Gitanos or Cale
      -a study of 83 cases.
AB  - This paper studies 83 cases of oculocutaneous albinism (OCA) in family networks
      of Gitanos in southeastern Spain, and analyzes their sustained inbreeding
      patterns and complex genealogical relationships. It is based in the family and
      genealogy reconstitution of the Gitano population of 22 contiguous localities
      using ethnographic and historical demography methods. The study found a
      prevalence of OCA among Gitanos in the area of about 1: 1,200. Most of the cases
      belong to three extended kin networks in which consanguineous marriages have been
      common for generations. In these networks there are other cases of visual and
      auditive congenital anomalies, and other birth defects such as brachydactily,
      polydactily, neurological defects, Potter Sequence, etc. In 61 OCA cases it was
      possible to trace inbreeding links with a depth of three to nine generations. For
      these cases the estimated alpha (average of the inbreeding coefficient, F) is
      0.0222. Relationships between the parents of people affected are of three types:
      close, as between first or second cousins; distant, as between third or fourth
      cousins, and non-existent, as in mixed marriages. In most cases, however, persons
      with albinism are linked by multiple consanguineous links. Albinism seems to be a
      visible example of a high prevalence of birth defects in this minority,
      associated with founder effects, sustained inbreeding and high fertility rates.
      These conditions derive from Gitano's marriage preferences and pronatalist
      strategies. In turn, these strategies have to be related to the exclusion,
      persecution and segregation that Spanish Gypsies have suffered for centuries.

PMID- 24308210
TI  - Facial preferences in early adolescent girls: pubertal maturity predicts
      preferences maturity.
AB  - Despite numerous studies on perception of facial attractiveness in adults,
      preferences in adolescents remain poorly recognized. The aim of present study was
      to explore facial preferences in girls at early adolescence (11-14 years old) and
      compare them with preferences of women. All females evaluated the same 30 male
      faces, which were also assessed by independent judges for several perceived
      features. Regardless of age, girls assessed attractiveness much the same as
      women, and the strengths of their preferences for specific facial features were
      similar to those of women. Except for the youngest girls, pubertal maturity
      (measured as the time elapsed since the menarche and breast development)
      correlated positively with the similarity of the girls' attractiveness
      evaluations to those of adult women and with strength of preference for cues to
      good biological quality (skin healthiness and sexy appearance). This remained
      true even after controlling for age and psychosexual development, suggesting thus
      that sex hormones are involved in development of facial preferences in pubescent
      girls.

PMID- 24308211
TI  - Smoking habits according to metabolic traits in an island population of the
      eastern Adriatic Coast.
AB  - The study deals with the connection between metabolic syndrome (MS) and smoking
      habits of 1602 males and 828 females aged 18-97 years from the island of Hvar,
      Croatia. The age-adjusted prevalence of MS was higher in males (18.1-31.2%) than
      females (9.7-24.2%) by all five criteria that were defined, except the one by
      AHA/NHLBI. The overall prevalence of MS reached 12.9% by WHO using body mass
      index (BMI), 13.1% by EGIR, 14.5% by WHO using waist to hip ratio (WHR), 18.2% by
      NCEP/ATP III, 18.9% by AHA/NHLBI, and 26.7% by IDF criteria. The prevalence of
      smoking habits was similar in males (24.7%) and females (23.8%). The frequency of
      mild, moderate and heavy smoking was higher in males than females, 35.8:26.6%,
      31.0:27.0%, and 35.9:7.7%, respectively. Age and sex had significant influence on
      BMI and WHR, both being highest in male former smokers (28.15 kg/m2 and 0.973,
      respectively) and in female non-smokers (27.18 kg/m2 and 0.869, respectively).
      The appearance of arterial hypertension (HTN) differed according to frequency of
      smoking; males had higher prevalence than females using WHO and EGIR criteria of
      blood pressure > or = 140/90 mmHg, even after age adjustment. In males and
      females respectively, systolic HTN in non-smokers was 20.7:15.1%, in former
      smokers 17.9:15.2% and in current smokers 16.9:13.0%; diastolic HTN in non
      smokers was 19.8:12.7%, in former smokers 22.4:10.5%, and in current smokers
      11.3:9.1%. By NCEP, AHA, IDF criteria of blood pressure > or = 130/85 mmHg,
      arterial HTN was also more prevalent in males than females; systolic HTN in non
      smokers being 31.4:19.8%, in former smokers 29.9:12.7%, and in current smokers
      25.4:11.1%; and diastolic HTN in non-smokers was 20.5:11.5%, in former smokers
      24.8:11.3%, and in current smokers 14.7:9.4%. According to AHA/NHLBI and IDF
      criteria of high plasma glucose as > or = 5.6 mmoL/L, both males and females in
      all the three categories of smokers had glucose levels above the normal range
      (5.80-6.31 mmol/L in males and 5.80-5.91 mmol/L in females), except female
      current smokers (5.51 mmol/L). By WHO, EGIR and NCEP/ATP III criteria of high
      plasma glucose as > or = 6.1 mmol/L, only male non-smokers (6.31 mmol/L) and
      former smokers (6.24 mmol/L) had elevated levels. Considering normal HDL
      cholesterol as > 1.0 mmol/L in males and > 1.2 mmol/L in females, both males and
      females in all the three smoker's categories had HDL within normal range; females
      having higher HDL levels (1.52 mmol/L) than males (1.30 mmol/L). Considering
      normal value for triglycerides as < 1.7 mmol/L, male former smokers (1.76 mmol/L)
      and current smokers (1.81 mmol/L) had higher levels; and as a whole group
      triglycerides were higher in males than females, 1.66:1.37 mmol/L respectively.
      The prevalence of MS differed between males and females using various MS
      criteria. Both males and females had the highest prevalence of MS by IDF
      criteria; male former smokers 60.5%, female non-smokers 51.4%, male non-smokers
      53.8%, female former smokers 38.2%, and lowest in both male and female current
      smokers 39.8 and 33.0% respectively. In males, the lowest prevalence of MS was
      observed in non-smokers by AHA criteria (30.5%), in former smokers by WHO
      criteria (35.7%), and in current smokers using EGIR criteria (18.1%). Females in
      all the three smoker's categories had the lowest prevalence of MS using EGIR and
      WHO criteria. MS were less prevalent in current smokers than in non-smokers and
      former smokers.

PMID- 24308212
TI  - Obesity and systolic blood pressure in young adult men born small for gestational
      age.
AB  - Individuals born small for gestational age (SGA) are supposed to be at higher
      risk to develop cardiovascular disorders, and recent report showed that
      concurrent obesity influences blood pressure (BP) in SGA children. Our aim was to
      investigate the impact of obesity and birth weight on blood pressure values in
      young adult men born SGA and controls born after normal pregnancy, Normotensive,
      non-treated adult men were enrolled (N = 185; mean age 21.29 +/- 0.9 years).
      Birth parameters were obtained from medical records and SGA was defined as birth
      weight (BW) under 10th percentile for gestational age and obesity as BMI > 25
      kg/m2. According to the presence or absence of obesity and BW the subjects were
      divided into four groups: (1) non-obese with normal BW (N = 50), (2) non-obese
      SGA (N = 67), (3) obese with normal BW (N = 40), (4) obese SGA (N = 28). BP was
      measured using Omron M6 and Spacelab 90207 device following the ESH/ESC
      guidelines. Systolic BP, 24-hour BP variability and pulse pressure were
      significantly higher in SGA subjects than in those with normal BW (p < 0.05). The
      highest 24-hour and daytime systolic BP values as well as 24-hour pulse pressure
      were found in the subgroup of obese SGA subjects (p < 0.001). Significant
      differences for the above parameters were observed between obese SGA group and
      non-obese SGA group (p < 0.05). Obese SGA subjects had higher 24-hour and daytime
      systolic BP values compared to obese normal BW group. No difference was found in
      BP between non-obese SGA and non-obese group with normal BW (p > 0.05). In
      addition to BW and shorter pregnancy duration, obesity concurrently and
      significantly determines systolic BP in young normotensive men and point to a
      need for more aggressive implementation of healthy lifestyle as early as
      possible.

PMID- 24308213
TI  - Hypertension, overweight and obesity in adolescents: the CRO-KOP study.
AB  - The objective of this study was to determine the prevalence of hypertension,
      overweight and obesity in Croatian adolescents. In this cross-sectional survey
      (the sub-study of the EH-UH study) 375 boys and 381 girls (mean age 15.9 +/- 0.5
      years) from four high schools in the city of Koprivnica were enrolled. Blood
      pressure, body height and body weight were measured according to the current
      ESH/ESC guidelines. Data on life style were obtained from questionnaire. Average
      blood pressure values were higher in boys than in girls (117/74 mmHg vs. 111/69
      mmHg; p < 0.001). Significantly higher blood pressure values were obtained in
      overweight children compared to those with normal weight (119/76 mmHg us. 115/72
      mmHg; p < 0.01). Prevalence of hypertension was 8.5% in the whole group being
      significantly higher in boys than in girls (11.2% vs. 5.8%; p = 0.0007). As
      expected, prevalence of hypertension was significantly higher in obese children
      than in those with normal weight (20.0% vs. 6.8%; p = 0.015). A significant
      correlation was found between body mass index and blood pressure (p = 0.0001).
      The overall prevalence of obesity was 3.54% (boys 2.2%; girls 4.9%). Our results
      confirmed positive relationship between overweight, obesity and hypertension
      starting from childhood pointing again the utmost importance of preventive
      measures beginning from early life.

PMID- 24308214
TI  - Impact of angiotensin-converting enzyme gene polymorphism on proteinuria and
      arterial hypertension.
AB  - Proteinuria is the hallmark of renal disease. In essential hypertension the onset
      of de novo proteinuria is associated with faster rate of progression of disease.
      Some authors have suggested that the DD genotype of the angiotensin-converting
      enzyme (ACE) gene would be an adverse renal prognosis factor. It may also have
      different effects on the reduction of proteinuria by ACE inhibitors in patients
      with proteinuria. Observations on the association between the ACE gene
      polymorphism and hypertension have been inconsistent, which might be due to
      ethnic and geographical variations. In this study was to investigated the
      relationship between ACE gene polymorphism and antiproteinuric effect of ACE
      inhibitors (ramipril) and to evaluate the possible association between I/D
      polymorphism and hypertension. We recruited 66 hypertensive patients (male 42,
      female 24) with overt proteinuria (urinary protein excretion over 500 mg/day).
      Patients were classified into three groups in accordance with ACE genotypes (17
      DD; 35 ID; 14 II). They were treated with ramipril and prospectively followed up
      for one year. Various clinical parameters including age, body mass index (BMI),
      24-h urine protein, creatinine, creatinine clearance (Ccr), systolic and
      diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP) were
      measured in the pre- and post-treatment periods. The ACE gene
      insertion/deletion(I/D) polymorphisms in intron 16 were determined by PCR.
      Results showed that there were no significant differences in the clinical
      parameters such as age, gender, serum creatinine, Ccr, SBP, DBP, MAP, and daily
      urinary excretion of protein among three groups (P > 0.05). ID genotype patients
      were found to have lower BMI (p = 0.031). ACE inhibition significantly reduced
      proteinuria in all genotype groups (p < 0.05). The percentage reductions of 24-h
      urinary excretion of protein were significantly different between the genotype
      groups (p = 0.042) and for DD genotype were significantly greater than in ID
      (79.2 +/- 28.9% vs 49.2 +/- 64.8%, P = 0.015). The slope of SBP was the main
      factor related to the slope of the percentage reduction of proteinuria, however,
      a significant negative correlation coefficient between these parameters was found
      (rs = -0.382, p = 0.002). We failed to find significant difference in outcomes of
      treatments with ACE inhibitor between male and female according the I/D
      polymorphism of the ACE gene. D allele in the ACE genotype could be a useful
      genetic marker with important clinical, therapeutic and prognostic implications
      in recognizing patients with proteinuria that are at greater risk of renal
      damage.

PMID- 24308215
TI  - Total and LDL cholesterol are associated with glomerular filtration rate in
      normoalbuminuric type 1 diabetic patients.
AB  - Studies have generally suggested a positive association between dyslipidemia and
      chronic kidney disease, but sparse data are available on the relation of lipids
      and glomerular filtration rate in patients with normal renal function. We
      investigated the associations of serum lipids, including total, LDL, HDL, VLDL
      cholesterol, and triglyceride levels with estimated glomerular filtration rate
      (eGFR) in type 1 diabetic patients. Study included 313 normoalbuminuric type 1
      diabetic patients with normal or mild decrease (eGFR > 60 mL/min per 1.73 m2)
      renal function and before any interventions with statins, ACE inhibitors or
      angiotensin II receptor blockers. eGFR was significantly associated with total,
      LDL, and HDL cholesterol (r = -0.21, -0.18, and -0.17, respectively, for all p <
      0.05). Stratifying serum lipids for degree of eGFR, levels of total, LDL, and HDL
      cholesterol were inversely related to eGFR, but trends were significant only for
      total (5.1 vs 5.0 and 4.6 mmol/L) and LDL cholesterol (2.9 vs 2.8 and 2.4
      mmol/L). We have detected an association between eGFR and lipid abnormalities in
      type 1 diabetes in early stages. The study was conducted in patients with no
      therapeutic intervention. This may suggest that lipid abnormalities may play a
      role in the pathogenesis of renal impairment in type 1 diabetic patients.

PMID- 24308216
TI  - Association between red blood cell count and renal function exist in type 1
      diabetic patients in the absence of nephropathy.
AB  - Anemia is a prevalent finding in patients with type 1 diabetes, particularly in
      those with albuminuria or reduced renal function. We investigated the
      relationship between red blood cell count (RBC) and renal function in type 1
      diabetic patients with normal or mildly impaired renal function and urinary
      albumin excretion rate (UAE) < 30 mg/24 h. Study included 313 type 1 diabetic
      patients with estimated glomerular filtration rate (eGFR) > 60 mL min(-1) 1.73 m(
      2), and before any interventions with statins, ACE inhibitors or angiotensin II
      receptor blockers. UAE was measured from at least two 24-h urine samples.
      Hemoglobin (Hb), hematocrit (Hct), erythrocytes (E), serum iron and ferritin
      levels were significantly lower in subjects in the highest quartile of serum
      creatinine compared to those in lowest quartile (132 vs 148 g/L, 0.39 vs 0.42
      L/L, 4.5 vs 4.8 x 10(12)/L, 13 vs 18 micromol/L, and 25 vs 103 microg/L,
      respectively, for all p < 0.001). Hb and Hct levels were significantly lower in
      subjects in the highest quartile of UAE compared to those in lowest quartile (135
      vs 140 g/L, and 0.40 vs 0.41 L/L, respectively, for all p = 0.03). Finally, those
      with mildly impaired eGFR had significantly lower levels of Hb, Hct and E
      compared to those with normal eGFR or hyperfiltrating subjects (133 vs 140 g/L,
      0.38 vs 0.41 L/L, and 4.4 vs 4.7 x 10(12)/L, respectively, for all p = 0.01). We
      have detected that interplay between RBC and renal function parameters occurs
      even in type 1 diabetic patients with normal or mildly impaired renal function.

PMID- 24308217
TI  - Risk factors for microvascular atherosclerotic changes in patients with type 2
      diabetes mellitus.
AB  - Diabetes mellitus is a metabolic disorder primarily characterized by elevated
      blood glucose levels and by microvascular and macrovascular complications which
      increase the morbidity and mortality. The aim of this study was to assess whether
      in high risk patients with type 2 diabetes mellitus whose blood pressure and
      lipid levels are well controlled still exist risk factors for microvascular
      changes and target organ damage (nephropathy and retinopathy). In this case
      control retrospective study 326 patients (111 with nephropathy and/or retinopathy
      and 215 controls) were enrolled. Nephropathy or retinopathy was present in 10.1%
      and 26.9% cases, respectively. Only 71% of patients (no significant difference
      between cases and controls) were treated with antidiabetic drugs. Therefore their
      diabetes was not properly controlled (hemoglobin A1c was 7.96% in cases and 7.58%
      in controls). Patients with microvascular changes had significantly longer
      diabetes than the controls (p < 0.05) but there were no significant differences
      between these two groups concerning lipids concentrations. Statins and fibrates
      were used by significantly less (p < 0.05) patients with microvascular
      complications than by those without them (21.6% vs. 36.3% and 1.8% vs. 17.2%
      respectively). The results of this study suggest that the duration of the disease
      and adequate control of glycaemia in patients with type 2 diabetes mellitus are
      more important for microvascular complications than the serum lipoproteins
      levels. Lipid-lowering treatment might have an impact on microvascular
      complications in patients with type 2 diabetes, irrespectively of their serum
      lipid levels.

PMID- 24308218
TI  - The relationship between methylenetetrahydrofolate reductase C677T gene
      polymorphism and diabetic nephropathy in Croatian type 2 diabetic patients.
AB  - Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been shown to be
      associated with the development of diabetic nephropathy in many ethnic groups. In
      this study, we examined the correlation between MTHFR C677T polymorphism and
      microalbuminuria in patients with diabetes mellitus type 2 in Croatian patients.
      85 patients with diabetes mellitus type 2 were recruited. Patients were
      classified into two groups--with and without diabetic nephropathy according to
      urinary albumin excretion rate in urine collected during 24 hours. The C677T
      genotype was determined by real-time PCR analysis. The genotype frequencies were
      CC 36.5%, CT 42.3% and TT 21.2% in diabetic patients without nephropathy versus
      CC 39.4%, CT 45.4% and TT 15.2% in those with nephropathy. There was no
      statistically significant difference in allele distribution between patients with
      nephropathy and those without (p = 0.788). Our study did not show a correlation
      between mutations in the MTHFR gene and diabetic nephropathy in Croatian
      patients. Diabetic nephropathy is influenced by multiple risk factors which can
      modify the importance of MTHFR polymorphism in its development.

PMID- 24308219
TI  - Ambulatory blood pressure monitoring in diabetic hypertensive patients, single
      center report--preliminary results.
AB  - ABPM (ambulatory blood pressure monitoring) has been considered to be a useful
      tool for the diagnosis and management of arterial hypertension and is a better
      predictor of future cardiovascular events as compared with conventional office
      based BP measurements. Despite its potential values, ABPM is not yet widely used
      in many clinical offices mainly because of lack of knowledge and unavailability.
      Aims of this preliminary study are to determine the control of hypertension and
      circadian BP characteristics in patients referred to our Centre whom we enrolled
      in the "HRKMAT" Study-Croatian Registry of ABPM. Although patients included in
      HRKMAT Study had other risk factors for cardiovascular diseases, in this paper we
      analyzed differences between hypertensive diabetics (N = 20) and nondiabetics (N
      = 57). 24-hours ABPM was performed with an automated oscillometric device Mobil-O
      Graph NG Vers.20 and office BP using mercury sphygmomanometer. Average office BP
      was 139/90 mmHg, and average 24h ABPM was 130/82 mmHg. Majority of hypertensive
      patients used antihypertensive drugs (79.2%). Diabetic patients had higher
      systolic BP but lower diastolic BP. There were no statistically significant
      differences in dipping status, but earlier BP surge was noticed in reverse
      diabetic dippers than in reverse non-diabetic dippers. Though no significant,
      there was higher prevalence of WCH ("white coat hypertension") in diabetics, and
      we found MH (masked hypertension) in only two patients. These are preliminary
      results on ABPM from our centre and of HRKMAT registry. Further and more valuable
      data and results are awaited from the main HRKMAT database.

PMID- 24308220
TI  - Effects of lipoprotein lipase and peroxisome proliferator-activated receptor
      gamma gene variants on metabolic syndrome traits.
AB  - Peroxisome proliferator activated receptor-gamma (PPARG) and lipoprotein lipase
      (LPL) play important role in lipid homeostasis, insulin resistance and
      adipogenesis, and their gene variability could be considered as predictive
      genetic markers for metabolic syndrome (MetSy). The aim of the study was to
      estimate possible associations of PPARG (Pro12Ala) and LPL PvuII (+/-)
      polymorphisms with MetSy and its traits. Study included 527 subjects. According
      to the modified National Cholesterol Education Program Adult Treatment Panel III
      definitions, subjects were classified into the metabolic syndrome group and
      control group. Genotyping was performed using polymerase chain reaction
      restriction fragment length polymorphism methods. In the total sample, LPL
      variants were associated with waist circumference (chi2 = 7.263, d.f = 2, p =
      0.026) and with BMI (chi2 = 6.549, d.f = 2, p = 0.038), where PvuII (+/+)
      genotype carriers had the highest risk for increased waist circumference
      (specific PvuII (+/+) vs. others analysis chi2 = 7.033, p = 0.008) and increased
      BMI (specific PvuII( +/+) vs. others analysis chi2 = 5.154, p = 0.023). LPL gene
      variants were also associated with HDL-C levels (chi2 = 6.901, d.f = 2, p =
      0.032), where PvuII (-/-) genotype carriers had higher HDL-C values in comparison
      to others (specific Pvu (+/+) vs. others analysis chi2 = 6.504, p = 0.011).
      Furthermore, PvuII (-) allele carriers had significantly lower glucose (allele
      based analysis Add Value = -0.0878, chi2 = 5.878, d.f. = 1, p = 0.015).
      Significant interaction was detected between PPARG and LPL that affected HDL-C
      levels in male population (chi2 = 11.790, d.f = 1, p = 0.0006) in the manner that
      Ala/PvuII(+) contributed to the lowest HDL-C values (Specific Ala/ Pvu(+) vs.
      others analysis was chi2 = 11.750, p = 0.0006). According to obtained results LPL
      and PPARG gene variants could be susceptibility factors of obesity and lipid
      status, contributing to development of MetSy, particularly in males. Because of
      antiatherogenic function of HDL-C, the identification of genetic variants
      associated with HDL-C can provide useful information related to genotype
      phenotype relationships. Since the interplay between PPARG and LPL gene and
      gender seems to be significant it could point to the personalized behavioural
      recommendations for prevention of metabolic and cardiovascular diseases.

PMID- 24308221
TI  - Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
      in the early period after kidney transplantation.
AB  - The role of renin-angiotensin system inhibitors (ACE-inhibitors) or angiotensin
      receptor blockers (ARB) in the renal transplant recipients (RTRs) is incompletely
      defined and according to the current guidelines they should be initiated after
      six months post-transplantation. The aim of the present paper is to evaluate the
      efficiency and safety of early (within six months post-transplantation) versus
      late (after six months post-transplantation) initiation of ACE-inhibitors or ARB
      in RTRs. The study group compromised of 108 RTRs (50 male and 58 female) who
      received a kidney transplant. Beside other prescribed antihypertensive drugs all
      of them took and ACE inhibitors or ARB in order to achieve blood pressure
      control. For this analysis purpose, recipients were stratified into two groups
      according to the time of ACE inhibitors/ARB initiation into early (within six
      months post-transplantation) and late (after six months after transplantation)
      group. For each patient haemoglobin, serum creatinine and potassium levels were
      analyzed at the beginning of ACE inhibitors/ARB introduction and at the end of
      the first, third, sixth and twelfth month. In the 54 (50%) of the 108 patients
      ACE inhibitors/ARB were initiated within six months post-transplantation and in
      49 (90.7%) of them within three months (in 29 patients within one month; in 13
      within two months; in 7 within 3 months) post-transplantation. In additional 54
      (50%) patients ACE inhibitors/ARB were initiated, but after six months post
      transplantation. There was no statistically significant difference between the
      two groups related to age or gender and due to the duration of dialysis treatment
      before the transplantation. Analyzing the haemoglobin, creatinine and potassium
      serum levels after initiation of therapy with ACE inhibitors/ARB trough observed
      period we did not found any statistically significant difference in all measured
      parameters between the two groups of patients and also within the same group of
      patients. Therefore, according to experience from our Institution early
      initiation of ACE inhibitors or ARB appears to be safe in carefully selected
      recipients with relatively good early graft function.

PMID- 24308222
TI  - BCM--body composition monitor: a new tool for the assessment of volume-dependent
      hypertension in patients on maintenance haemodialysis.
AB  - Hypertension is a common finding in end-stage renal disease patients with the
      prevalence between 20 to 85%. Although the etiology of arterial hypertension (AH)
      in this patient group is multifactorial, sodium and volume excess leading to
      extracellular volume overload are one of the most important and potentially
      adjustable causes. Control of volume status can either normalize the blood
      pressure (BP) or make the AH easier to control in the great majority of dialysis
      patients. Heavy reliance is placed on the dialysis procedure to gradually remove
      fluid over a period of days to weeks until a stable dry weight is achieved.
      Numerous attempts have been made to utilize alternative methods to more
      accurately assessment of dry weight, and the newest and most interesting method
      is multifrequency bioelectrical impedance spectroscopy (BIS). In this prospective
      study we used BIS in 65 haemodialysis (HD) patients in order to detect those with
      volume-dependent hypertension and to further investigate the role of dry weight
      management in BP control. Dry weight was corrected at the beginning, and after 1,
      and 3 months. Final data were collected after six months. Our data showed that
      assessment of fluid overload using BIS provides better management of fluid status
      and BP control in the patients on maintenance HD, and that dry weight correction
      can lead to significantly better control of volume-dependent hypertension in this
      patient group.

PMID- 24308223
TI  - Importance of urinary NGAL, serum creatinine standardization and estimated
      glomerular filtration rate in resistant hypertension.
AB  - In patients with resistant hypertension (RH) we investigated the importance of
      urinary neutrophil gelatinase-associated lipocalin (uNGAL- a chemiluminescent
      microparticle immunoassay (CMIA) method became using (Abbott Diagnostics) for the
      measurement of NGAL in urine samples) and incidence of chronic kidney disease
      using the Modification of Diet in Renal Disease Study (MDRD) and Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) equations in estimating glomerular
      filtration rate (eGFR) based on standardised serum creatinine method traceable to
      isotope dilution mass spectrometry (IDMS) method. It would have been difficult to
      predict that levels of these biomarker would perform better organ damage than
      traditional measurements of kidney function such as standardised serum
      creatinine, MDRD, or CKD-EPI equations in special population such as RH. Serum
      creatinine concentrations were measured in 50 patients (24M:26F from RH Registar
      in Clinical Hospital Merkur) by the kinetic Jaffe method. There were no
      significant differences between the GFR values derived by MDRD and CKD-EPI
      equations in the group of patients with RH. 62% of patients have eGFR > 60
      mL/minl/1.73 m2, while a 38% of patients have eGFR < 60 mL/min/1.73 m2. The
      measurement of NGAL in urine samples of 40 patients with RH showed no difference
      and seems to be of no use in further determination of renal impairement. Higher
      value of uNGAL in some resistant hypertension patients could have link in the
      repair stage after AKI and would reveal pathways that could link AKI and CKD.

PMID- 24308224
TI  - Survival of patients treated with online hemodiafiltration compared to
      conventional hemodialysis.
AB  - Accumulating data from observational studies showed that online hemodiafiltration
      (OLHDF) might improve survival in chronic hemodialysis (HD) patients. According
      to this data, the aim of our study was to investigate whether there was a
      difference in survival of patients treated with OLHDF compared to standard,
      conventional HD. We included 85 prevalent patients with end-stage renal disease
      (ESRD) treated with HD as a method of renal replacement therapy (RRT) for more
      than three months. Patients were previously treated with HD and divided into two
      groups: in 42 patients new treatment with OLHDF was introduced, and 43 patients
      were treated with HD. Both groups were followed over a period of 36 months. The
      study showed significantly better survival of patients treated with OLHDF,
      compared to the survival of patients treated with HD in the whole study
      population, as well as in the subgroups of diabetics, of patients who were on RRT
      with HD for more than five years and of the patients who were older than 65
      years. In the nondiabetics, patients who were on RRT for less than five years and
      in the patients who were younger than 65 years, survival results in the OLHDF
      group were not significantly better compared to those in the HD group. As in our
      study, there are accumulating data from observational studies that HDF may
      improve survival in chronic HD patients, but new, prospective randomized trials
      are needed to support evidence about this hypothesis.

PMID- 24308225
TI  - Definition of acetylsalicylic acid resistance using whole blood impedance
      aggregometry in patients undergoing coronary artery surgery.
AB  - A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been
      described, but some patients experience adverse cardiac events despite
      appropriate ASA treatment. Study aim was to define ASA resistance using Multiple
      electrode aggregometry (MEA) preoperatively in group of patients undergoing
      coronary artery bypass grafting (CABG). Prospective observational trial at
      University Hospital Center Zagreb enrolled 131 patients scheduled for CABG, and
      divided them into 4 groups with respect to preoperative antiplatelet therapy
      (APT). Group 1 received 100 mg ASA per day, Group 2 100 mg ASA + 75 mg
      clopidogrel per day, Group 3 75 mg clopidogrel per day, and Group 4 did not
      receive any APT. MEA with ASPI test (sensitive to ASA) and ADP test (sensitive to
      clopidogrel) was performed prior to surgery. In Group 1, patients were
      characterized as ASA resistant if their ASPI test value exceeded the 75th
      percentile distribution. Study enrolled 131 patients. Significant differences
      both in the ASPI (p < 0.001) and the ADP test (p = 0.038) were observed between
      patients in different APT groups. In Group (1) ASPI test value of 30 AUC
      presented 75th percentile of distribution, thus indicating ASA resistance. Group
      2 patients had slightly lower ADP test values, but no significant difference
      occurred (mean 60.05 vs. 63.32 AUC, p = 0.469). In Group 1 and 2, significant
      correlations between the ADP test and both, platelet count (r = 0.347, p < 0.001)
      and fibrinogen level (r = 0.364, p < 0.001) were observed. Association between
      low response to ASA and post-CABG major adverse ischemic events risk increase has
      been described thus indicating need for ASA resistant patients detection. In
      patients with preoperative ASPI test exceeding 30 AUC postoperative, ASA dose
      adjustment or clopidogrel addition according to MEA results should be considered.

PMID- 24308226
TI  - Macular thickness after glaucoma filtration surgery.
AB  - The aim of present study was to analyze early postoperative changes in the
      macular area using optical coherence tomography (OCT) after uncomplicated
      glaucoma filtration surgery. This prospective study included 32 patients (34
      eyes) with open-angle glaucoma, which underwent trabeculectomy with or without
      use of mitomycin C. Exclusion criteria were macular edema, uveitis, age-related
      macular degeneration, blurred optical media, secondary glaucoma and angle-closure
      glaucoma. All standard clinical examinations were made before surgery, at the 2nd
      day, 1 week and 1 month after surgery. Tomography of the macula was performed
      during every examination using Cirrus HD OCT for the analysis of central subfield
      thickness. Results show that thickening of the macula was slightly higher 1 week
      and 1 month after operation in comparison with baseline end 2nd day
      postoperativelly. There was no significant difference in the change of macular
      thickness in patients who have used topical prostaglandins compared with those
      who have used other topical medications. Also, there was no difference in macular
      changes between patients treated with or without mitomycin C. In conclusion, we
      found a slight subclinical increase in macular thickness after uncomplicated
      trabeculectomy, for which we considered that was the result in reduction of
      intraocular pressure after glaucoma surgery. Macular thickening after glaucoma
      filtering surgery could be a physiological reaction to the stress of the retina
      caused by a sudden reduction of intraocular pressure and it is the consequence of
      altered relationship between capillary pressure and interstitial fluid pressure.

PMID- 24308227
TI  - The role of C-Fos protein, somatostatin and neuropeptide Y in the pathogenesis of
      ischemic brain injuries based on animal model of cerebral ischemia.
AB  - The aim of this study was to define all the areas of changes in expression of
      nuclear c-Fos protein (c-Fos), cytoplasmic somatostatin (SS) and neuropeptide Y
      (NPY) in rat brain during experimental ischemia. Using the immunohistochemical
      method, brain mapping (based on the atlas by Paxinos & Watson) of
      immunoreactivity for c-Fos, SS and NPY in 39 rats, was studied in telencephalon,
      diencephalon and midbrain after resistant and transitory ischemia. The first
      experimental group (R group) was exposed to resistant ischemia by occlusion (10
      minutes) of four vessels according to the Pulsinelli method. The second group was
      first exposed to transitory (4 minutes) ischemia (preconditioning) and, after 72
      hours, to total ischemia as in the R group. There was a statistical difference
      between the R and T group in the c-Fos reaction, especially in the parietofrontal
      cortex, anterior amygdaloid area, claustrum, reuniens nucleus and suprachiasmatic
      nucleus. The dominant immunohistochemical reactivity was found for c-Fos protein,
      and the most reactive in terms of co-localization of c-Fos with SS and NPY was
      periventricular area of hypothalamus. The mapping showed that both,
      phylogenetically new as well as phylogenetically older brain structures reacted
      immunohistochemically. The results of our study, regarding the impact of
      preconditioning with a short period of ischemia on c-Fos activity and co
      localization of c-Fos with SS and NPY immunoreactivity, showed the need for
      future studies of brain neuropeptides related to regional and time effects, and
      indicated brain structures which may require pharmacological targeting to achieve
      neuroprotective level of proto-oncogene activity in populations at risk.

PMID- 24308228
TI  - Somatotype of elite Italian gymnasts.
AB  - The somatotyping method is especially helpful in sports in which the body could
      directly influence the biomechanics of movements and the performance's results.
      The purpose of this study was to determine the somatotype of elite Italian
      gymnasts and to compare it in terms of competition levels. The sample comprised
      64 elite gymnasts (42 females (F), somatotype 1.4-4.4-3.2; and 22 males (M),
      somatotype 1.6-6.3-2.1) belonging to the Italian National Artistic Gymnastic Team
      (2007) at different competition levels: Allieve, Junior, and Senior. Mean whole
      somatotypes, by competition levels, were not significantly different in both
      sexes (Female gymnasts: Allieve, 1.3-4.6-3.3; Junior, 1.3-4.2-3.6; Senior, 1.7
      4.2-2.7; Male gymnasts: Junior, 1.5-6.3-2.5; Senior, 1.7-6.3-1.6). Male Junior
      gymnasts exhibited greater ectomorphy than Senior athletes (F1,20 = 7.75, p <
      0.01). Compared to other elite athletes male and female gymnasts tend to be less
      endomorphic and more mesomorphic. This study highlighted the peculiarities of the
      somatotype of Italian elite gymnasts and their strong homogeneity, evident also
      from the low values of somatotype attitudinal mean (SAM). The results emphasize
      the need for a specific somatotype to reach an elite level in sport and the need
      to integrate the somatotype analysis between the scientific instruments for
      selecting talent also in artistic gymnastics.

PMID- 24308229
TI  - Bilateral concentric and eccentric isokinetic strength evaluation of quadriceps
      and hamstrings in basketball players.
AB  - The aim of the study was to investigate the existence of bilateral asymmetry in
      healthy basketball players of different age, as evidence suggest that it may be
      an age related phenomenon which develops over the years of training. Fifty
      healthy basketball players (26 males and 24 females) participated in the study.
      The quadriceps (Q) and the hamstring (H) were tested concentrically and
      eccentrically at 60 degrees/s. The main outcome measure was body weight
      normalized peak torque (PT/BW). We have also calculated different strength ratios
      as well as the bilateral strength differences. The main findings indicate that
      (1) bilateral strength asymmetry is noticeable in senior basketball players
      relating predominantly to the Q (2) some gender related strength differences were
      mainly associated with the concentric strength of Q and H (3) when corrected for
      weight and height, age related strength differences were relatively small and
      observed only with respect to H strength in males (4) superiority of eccentric
      over concentric strength values of Q and H was more pronounced in females than in
      males. Strength asymmetry in senior basketball players may be more attributable
      to the better neuromuscular control during vertical jumping than to the strength
      itself as there were no age related differences between cadets and senior
      players.

PMID- 24308230
TI  - Blood lactate level responses and comparison with submaximal running and roller
      skiing in cross-country skiers.
AB  - The purpose of this study is to examine the effect of 30-minute duration
      submaximal running and roller skiing exercises, which are among the most
      important aerobic exercise models in cross-country skiers, on lactic acid levels.
      The study group comprised 6 female and 4 male athletes (age: 16.87 +/- 1.87
      years, body height: 168.35 +/- 5.66 cm, body weight: 56.83 +/- 7.1 kg) who
      competed in cross-country skiing at national and international level. All
      athletes participated in the study voluntarily. Measurements were performed three
      times as basal (1st measurement), immediately after exercise (2nd measurement)
      and 5 minutes after finishing exercise (3rd measurement).Statistical analysis was
      conducted using SPSS (version 11.5). A significant increase (P < 0.01) in lactic
      acid levels was found for both 30-minute submaximal exercise types; however, this
      effect did not differ statistically between groups. Running exercises caused
      greater fatigue than skiing exercises, according to percentage values, but the
      difference in fatigue levels between exercise types was not statistically
      significant.

PMID- 24308231
TI  - Urinary tract infection (UTI) in newborns: risk factors, identification and
      prevention of consequences.
AB  - The aim of the study is identification of urinary tract infections (UTI) and
      urinary tract anomalies (UTA) already in the perinatal period. The authors
      attempted to prevent serious consequences of the above conditions in the examined
      children. Family history data, certain conditions in pregnancy and appertaining
      symptoms in children were elaborated to specify selective distinctive criteria
      for children at risk. Newborns (1200) were selected for potential existence of a
      UTI. All the examined newborns underwent a urinalysis. Those with significant
      bacteriuria were taken urine specimens, C-reactive protein (RVP), Complete Blood
      Count (CBC) and bilirubin. The newborns with a UTI and a suspected UTA were sent
      to ultrasound examination, direct radio nuclide cystography and Tc99m MAG3
      dynamic scanning. The frequency of a UTI in the perinatal period amounted to
      4.5%. A UTA was found in 29.6% of the examinees. The infection was more likely to
      appear among newborns with a UTA in their families, a UTI, pre-eclampsia and a
      febrile infection in mother, intrauterine growth retardation, premature rupture
      of membranes (RVP), umbilical cord strangulation, jaundice, cyanosis, breathing
      difficulties, seizures and asphyxia.

PMID- 24308232
TI  - Prevalence of third molars and pathological changes related to them in dental
      medicine.
AB  - The purpose of this study was to determine the prevalence of third molars in
      terms of respondents' age. Furthermore it was desired to determine the extent of
      the manifestation of pathological changes, such as caries, apical lesions, and
      alveolar bone resorption. This study was based on 500 OPGs of patients from the
      Faculty of Dentistry, University of Zagreb. Patients were divided into seven age
      groups. The total number of molars, the number of cavities on remaining molars,
      the quality of endodontic treatment and the evaluation of their performance and
      presence of periapical lesions was analyzed. As apart of the periodontal status,
      the number of inadequate fillings, the number of damaged furcations and bone
      resorption was analyzed. The statistical analysis was performed by means of
      STATISTICA 7 statistical package (StatSoft, Tulsa, USA). The correlation between
      the total number of molars and the age of patients was analyzed by means of
      Spearman's correlation to the level of significance of 0.05. The number of first,
      second and third molars significantly decreased in higher age groups. The
      prevalence of caries in third molars as compared to first and second molars was
      generally lower, third molars were endodontic treated at least. Assessment of
      involved furcations showed that the lowest percentage of 8% was found in third
      molars. The majority of all remaining molars had bone resorption of 1-3 mm.

PMID- 24308233
TI  - Multiple lingual cusps trait on mandibular premolars and hypoconulid reduction
      trait on mandibular first molar in living Jordanian population. Intra- and inter
      trait interactions.
AB  - The objective was to determine the expression and fluctuating asymmetry of two
      dental morphological traits in the living Jordanians: The lingual cusp number on
      the lower premolars (LP1 and LP2) and the hypoconulid (distal cusp) reduction on
      the lower first molar (LM1). In addition, both intra- trait and inter- trait
      interactions were analyzed. Three hundred school children (15.5 +/- 0.4 years)
      were involved. Impressions for the mandibular dental arches were taken, and
      dental casts were reproduced. The above-mentioned traits were observed. Paired
      sample t test and nonparametric correlation analysis were used for data analysis.
      Three-cusped LP1 was found in 11.40 % of the examined students, while the two
      cusped LP1 was found in 88.60%. In comparison, the Three-cusped LP2 was found in
      61.40% while the two-cusped LP2 was found in 38.60% of the observed subjects. The
      frequencies of the 4-cusped and 5-cusped LM1 were found to be 8.65% and 91.35%,
      respectively. Nonparametric correlation analysis revealed positive and
      statistically significant association between the expression of two lingual cusps
      on LP1 and on LP2 in both genders (p < 0.01), while there was no significant
      correlation between expression of two lingual cusps on either LP1 or LP2 and the
      hypoconulid loss on LM1 in both genders (p > 0.05). Bilateralism was highly
      significant in the tested traits in both genders (p < 0.001). This finding might
      be a sign of relatively low environmental stresses experienced by the living
      Jordanians and/or great ability of its individuals to buffer the adverse effects
      of such stresses on dental development. This study is a useful addition to the
      existing literature in that it examines a previously poorly characterized
      population and assists in placing the contemporary Jordanian population within
      the current framework of human population groups globally.

PMID- 24308234
TI  - Comparison of vertical forces during root canal filling with three different
      obturation techniques.
AB  - The aim of this study was to examine and compare vertical forces exerted during
      root canal obturation with the cold lateral condensation technique, Thermafil
      technique and ProTaper guttapercha. Fourty-five single-rooted permanent teeth
      were used in the study. All specimens were instrumented using the ProTaper
      rotating technique and were randomly divided into three experimental groups (n =
      15 per group). In the first group, root canals were obturated using the cold
      lateral condensation technique. In the second group, the Thermafil technique was
      used to obturate root canals. In the last group, a ProTaper gutta-percha of the
      same taper as the instrumented root canals was used for root canal obturation.
      Vertical forces were measured using the device developed for simulation of
      endodontic treatment. The results showed a statistically significant difference
      (p = 0.0001) for vertical forces when cold lateral condensation obturation
      technique was used in comparison to other techniques. No statistically
      significant difference was found for vertical forces during obturation with
      Thermafil and ProTaper gutta-percha (p = 0.16). The cold lateral condensation
      technique exerted higher vertical forces in comparison to the Thermafil and
      ProTaper obturation techniques.

PMID- 24308235
TI  - Disc and condylar head position in the temporomandibular joint with and without
      disc displacement.
AB  - The purpose of this study was to evaluate the difference between disc and condyle
      position between temporomandibular joints (TMJs) without disc displacement (DD)
      in asymptomatic volunteers, and patients who have DD in contralateral joints,
      respectively unilateral DD. Secondly, there were two TMJ groups which consisted
      of measurements from patients' symptomatic DD and volunteers with asymptomatic
      DD. The study included 79 TMJs of 40 patients with unilateral DD. In the group of
      25 asymptomatic volunteers, 20 volunteers were without DD bilaterally (40
      joints), while five had DD in at least one TMJ. All subjects were examined
      clinically and DD was confirmed by magnetic resonance imaging. Left and right
      TMJs were analysed independently for each participant based on their DD status
      (symptomatic, asymptomatic, and without DD). All asymptomatic TMJs did not have
      any clinical signs of TMJ functional abnormalities. There was a significant
      statistical difference between disc position among TMJs without DD in
      asymptomatic volunteers and TMJs without DD in patients (p = 0.016). Moreover, no
      significant differences were found between condyle position in the same groups of
      joints (p = 0.706). There were no significant differences in the DD position (p =
      0.918) or condyle position (p = 0.453) between the group with asymptomatic
      volunteers' joints and the group with symptomatic patients' joints. There was a
      significant difference between patient and volunteers' joints without DD: the
      disc was positioned more anteriorly in patients' joints without DD than in joints
      of asymptomatic volunteers without DD.

PMID- 24308236
TI  - Interleukin-6 polymorphism and prostate cancer risk in population of Eastern
      Croatia.
AB  - Recent studies suggest that chronic inflammation is crucial in the development
      and progression of prostate cancer (CaP). Interleukin-6 (IL-6) is a
      proinflammatory cytokine that plays an important role in intraprostatic
      inflammation and thus carcinogenesis. The -174G > C polymorphism of IL-6 gene has
      been associated with high IL-6 producer phenotype and an increased risk for CaP.
      The aim of this study was to evaluate the association between the mentioned IL-6
      polymorphism and CaP risk, as well as to compare the genotype frequency between
      the different tumour grades of CaP, in population of Eastern Croatia. We analyzed
      the IL-6 polymorphism in 120 CaP patients and 120 controls with benign prostatic
      hyperplasia (BPH). CaP patients and BPH controls did not statistically differ in
      studied IL-6 polymorphism. Furthermore, high IL-6 producer genotypes (GG or GC)
      were more frequent in controls than in CaP group (86.7% vs 80.8%, respectively, p
      = 0.147). Also, no statistically significant difference in IL-6 high and low
      producer genotype frequency was noticed between well, moderately and poorly
      differentiated tumours. Our results, taken together with other studies on the
      subject, suggest that IL-6 - 174 single nucleotide polymorphism (SNP)
      distribution may differ between various ethnic groups and that a single cytokine
      gene polymorphism has probably just a minor effect on CaP susceptibility. Further
      studies should be performed to clarify the link between SNPs of different
      cytokines and the risk for CaP.

PMID- 24308237
TI  - First six years of implementing colorectal cancer screening in the Osijek-Baranja
      County, Croatia--can we do better?
AB  - The primary goal of this paper is to evaluate the efficiency of the Colorectal
      Cancer Screening Program in the Osijek-Baranja County. The screening method for
      early detection of colorectal cancer was the guaiac Faecal Occult Blood Test
      (gFOBT) and colonoscopy for gFOBT positive finding. The target population were
      asymptomatic subjects at average risk, aged 50-74. The responding rate was 20.3%
      (14.9% of men and 19.3% of women). The percentage of gFOBT positive tests was
      8.5% (11.2% of men and 6.6% of women). From the 1,657 individuals who were
      invited to further assessment (884 men and 773 women), 1,157 underwent a
      colonoscopy exam (649 men and 508 women). We can conclude that the response to
      FOBT in our county was extremely poor. 83 carcinomas were found, with almost
      double findings among men than among women. Our population has a significantly
      higher number of men with malignant and premalignant changes when compared with
      women. Considering the higher incidence among men, as well as an increase in
      incidence in the entire population, we have to take care that our public health
      programmes are being created with this taken into account, as to increase the
      response rate, especially among those with a higher risk of developing a disease.

PMID- 24308238
TI  - Clinical expression of inflammatory bowel diseases--a retrospective population
      based cohort study; Vukovarsko-Srijemska County, Croatia, 2010.
AB  - Clinical characteristics of the cohort of 150 patients with inflammatory bowel
      diseases, ulcerative colitis (UC) and Crohn's disease (CD), Vukovarsko-Srijemska
      County, Croatia, were retrospectively assessed. UC was clinically presented with
      frequent passage of bloody, slimy stools, while preferential symptoms of CD were
      fever, anemia and severe weight loss, differences reflecting longer duration of
      symptoms prior to the diagnosis, in patients with CD. The prevalent disease
      localisations, in patients with UC, were the rectum and the left colon and the
      anorectum, while the prevailing phenotype, in patients with CD, corresponded with
      younger adult age at disease onset, ileocolonic localization and stricturing
      disease behavior Intestinal complications, including perforation, fistula,
      abscess and ileus, were more prevalent in patients with CD. Of extraintestinal
      complications, only ankylosing spondylitis and erythema nodosum, reached
      marginally significant differences, in favor to patients with CD. Shortcomings of
      this study include the lack of associations and the time-dependent disease
      projections.

PMID- 24308239
TI  - Expression of genes responsible for the repair of mispaired bases of the DNA
      (MLH1) in invasive ductal breast carcinoma.
AB  - Breast cancer is a heterogeneous group of diseases determined and distinguished
      by cellular type, gene expression and clinical signs and symptoms. Identification
      of histological and biological markers is of great value in predicting the
      progression of tumor growth and anticipating the expected response to various
      treatment options. Due to a high degree of cell proliferation in breast tumors
      and high genetic instability of these tumors, as a consequence of defective DNA
      repair mechanisms, chemotherapy as a treatment option often renders very
      successful results. During our scientific research we wanted to determine the
      involvement of the genetic polymorphisms of DNA mismatch repair system (MLH1
      gene) and the subsequent development of breast carcinoma. This study included 108
      patients who were surgically treated for invasive breast cancer at the Department
      of Plastic, Reconstructive and Aesthetic Surgery, University Hospital "Dubrava".
      The expression of the MLH1 gene was determined by immunohistochemical methods.
      The results showed that 82.9% of tumor cells expressed the MLH1 gene. Analysis of
      survival rate for patients with invasive ductal breast cancer showed a
      statistically significant (p = 0.043) correlation with the expression of MLH1
      genes. The overall five year survival rate of our patients was 78.7%. These
      results indicate that there is a possible involvement of MLH1 gene in the
      progression and development of breast cancer.

PMID- 24308240
TI  - Periodontal disease increases risk for chronic obstructive pulmonary disease.
AB  - The aim of this study was to explore whether a periodontal disease could be a
      risk indicator for a chronic obstructive pulmonary disease (COPD). The examined
      group comprised 93 patients with COPD (mean age 65.8 years). The control group
      comprised 43 systemically healthy individuals (mean age 62.1 years). Respiratory
      and periodontal conditions were examined in both groups. COPB subjects had
      significantly worse periodontal conditions than controls (p < 0.05) with regard
      to each parameter of periodontal condition, except for gingival inflammation.
      COPD patients had higher Plaque Index than control patients (82.84 +/- 22.81 vs.
      57.15 +/- 26.96; p < 0.001), higher periodontal depth (3.02 +/- 0.92 vs. 2.57 +/-
      0.79 mm; p = 0.007), higher gingival recession (1.97 +/- 1.09 vs. 0.91 +/- 0.79
      mm; p < 0.001), and higher mean clinical attachment loss (CAL) (4.12 +/- 1.74 vs.
      2.91 +/- 1.27 mm; p < 0.001). Multiple logistic regression model, after
      controlling for other risk indicators, showed that periodontal disease, presented
      as CAL > or = 4 mm at > or = 60% sites, was associated with odds ratio of 3.2
      (95% CI 1.0-9.8) for the COPB group. Data suggest that periodontal disease could
      be a risk indicator for COPD.

PMID- 24308241
TI  - West Nile virus outbreak in humans in Croatia, 2012.
AB  - During August and September 2012, seven cases of West Nile neuroinvasive disease
      were identified in three north-eastern counties of Croatia. Four cases were
      reported in Osijek-Baranja County, two in Brod-Posavina County and one in Vukovar
      Srijem County. The median age of the patients was 62.7 years. All patients were
      hospitalized for 2-5 weeks. The patients from Slavonski Brod had more severe
      clinical presentation of disease with prolonged hospitalization. Medical
      entomological research was carried out in 64 localities, where 1785 mosquitoes
      were captured. Among the analyzed mosquitoes, 114 were determined to be Culex
      pipiens and subjected to molecular characterization for the presence of virus. No
      viral RNA was detected in mosquitoes. Subsequent public health measures taken
      include mosquito control in all settlements where disease was detected.

PMID- 24308242
TI  - Equine seroprevalence rates as an additional indicator for a more accurate risk
      assessment of the West Nile virus transmission.
AB  - The West Nile Virus (WNV) is a zoonotic arbovirus that has recently been causing
      outbreaks in many countries in southern and Central Europe. In 2012, for the
      first time, it caused an outbreak in eastern Croatia with total of 7 human
      clinical cases. With an aim of assisting public health personnel in order to
      improve survey protocols and vector control, the high risk areas of the WNV
      transmission were estimated and mapped. The study area included cities of Osijek
      and Slavonski Brod and 8 municipalities in Vukovarsko-Srijemska County. Risk
      estimation was based on seroprevalence of WNV infections in horses as an
      indicator of the virus presence, as well as the presence of possible WNV mosquito
      vectors with corresponding vector competences. Four mosquito species considered
      as possible WNV vectors are included in this study: Aedes vexans, Culex modestus,
      Culex pipiens and Ochlerotatus caspius. Mosquitoes were sampled using dry-ice
      baited CDC trap, twice a month, between May and October. This study suggests that
      the two mosquito species present the main risk of WNV transmission in eastern
      Croatia: the Culex pipiens--because of good vector competence and the Aedes
      vexans--because of the very high abundances. As a result, these two species
      should be focus of future mosquito surveillance and a vector control management.

PMID- 24308243
TI  - Heavy metals and metalloid content in vegetables and soil collected from the
      gardens of Zagreb, Croatia.
AB  - Aim of this study was to determine concentration of Pb, Cd, As and Hg in green
      leafy vegetables and soil in the urban area of Zagreb, Croatia and to determine
      if there is a connection between the contamination of soil and vegetables. Green
      leafy vegetables and soil samples were taken from the gardens located in the
      outskirts of the city. Concentrations of Pb, Cd, As and Hg were determined by
      atomic absorption spectrometry; showing that average concentrations of metals and
      metalloids in vegetables and in soil, regardless of the location of sampling were
      below the maximum allowed concentration (MAC). The analysis determined that metal
      concentrations in only nine vegetable samples (9%) were above maximum allowed
      values prescribed by national and European legislation (three with higher
      concentrations of Pb, one with a higher concentration of Cd and five with higher
      concentrations of Hg). Concentrations of contaminants present in the analysed
      samples, in general, are lower than the ones published in similar studies. The
      final distribution and concentration of contaminants in vegetables of Zagreb,
      besides industry and traffic, is affected by the dominant wind direction.

PMID- 24308244
TI  - Effects of magnesium, chromium, iron and zinc from food supplements on selected
      aquatic organisms.
AB  - The aim of this study was to determine the effect of uncontrolled environmental
      disposal of food supplements containing magnesium (Mg), chromium (Cr), iron (Fe)
      and zinc (Zn) on selected aquatic organisms including freshwater algae
      Scenedesmus subspicatus and Raphidocelis subcapitata, water flea Daphnia magna
      and duckweed Lemna minor. Thirty different food supplements containing Mg, Cr, Fe
      and Zn were analyzed. Results were expressed as effective concentration 50
      (EC50), i.e. growth inhibiting Mg, Cr, Fe and Zn (mg/L) concentration
      immobilizing 50% of treated organisms. Particular metal EC50 differed
      significantly (p < 0.001) among study organisms, as follows (in ascending order):
      Scenedesmus subspicatus EC50 Fe (median 46.9 mg/L) < Zn (59.8 mg/L) < Mg (73.0
      mg/L) < Cr (88.1 mg/L) (KW-H(3;120) = 36.856; p < 0.001); Raphidocelis
      subcapitata EC50 Fe (median 44.9 mg/L) < Zn (52.6 mg/L) < Mg (62.2 mg/L) < Cr
      (76.8 mg/L) (KW-H(3;120) = 44.0936; p < 0.001); Daphnia magna EC50 Zn (median
      59.4 mg/L) < Cr (79.2 mg/L) < Fe (80.8 mg/L) Mg (82.0 mg/L) (KW-H(3;120) =
      39.2637; p < 0.001); and Lemna minor EC50 Zn (median 131.0 mg/L) < Fe (186.8
      mg/L) < Mg (192.5 mg/L) < Cr (240.4 mg/L) (KW-H(3;120) = 58.6567; p < 0.001).
      Uncontrolled environmental disposal of food supplements containing Mg, Cr, Fe and
      Zn exerts adverse effects on aquatic organisms. Therefore, legal provisions
      should regulate both the utilization and disposal of food supplements into the
      environment.

PMID- 24308245
TI  - Animal assisted therapy and perception of loneliness in geriatric nursing home
      residents.
AB  - Use of animals for therapeutic purposes, animal assisted therapy or AAT is a
      method for improving quality of life for long-term inpatients. The object of this
      paper was to evaluate dog companionship as a form of AAT and its effects on
      perception of loneliness in geriatric nursing home residents. The participants
      were involved in a six-month program of dog companionship three times weekly for
      90 minutes. There were 21 residents included in the program, with a mean age of
      80 years. Loneliness was measured by the short version of the UCLA Scale of
      loneliness. Comparison of test results before and after participation in the
      program showed that dog companionship reduces the perception of loneliness.

PMID- 24308246
TI  - GISTs' classifications in predicting aggressive behavior: a single institution
      experience.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      of the gastrointestinal tract. When making treatment plan it is very important to
      make proper tumor aggressiveness estimation. Traditionally, the best prognostic
      factors are tumor size and number of mitoses. The aim of this study was to define
      which GIST classification (Amin's or Newman's classification or Fletcher's
      Consensus Criteria) is the most significant determining prognosis and has the
      strongest impact on survival. This study included 63 GIST patients whose tumor
      specimens were evaluated by standard histopathological methods and classified
      based on histological assessment of malignant behavior to the three different
      systems. Comparison of those classification systems was done and none of them was
      proven to be statistically significantly better in predicting overall survival
      and probability of lethal outcome. We conclude that all three classifications are
      comparable in prediction of malignant behavior. The worst prognostic factor is
      existence of metastases at the time of disease diagnosis.

PMID- 24308247
TI  - Osteobiography of a 19th century elderly woman with pertrochanteric fracture and
      osteoporosis: a multidisciplinary approach.
AB  - In this paper the osteobiography of an elderly woman recovered from a cemetery
      tomb where she was buried in 1850, affected by hip fracture and osteoporosis, is
      described. The overall anthropological characteristics of the individual have
      been investigated. Macroscopic, radiographic, tomographic, microscopic, and
      chemical and structural examinations have been performed to give a detailed
      account of the condition of the skeleton. A non-union pertrochanteric fracture
      not surgically treated and probably due to senile osteoporosis was diagnosed. The
      consequences of the fracture to the bones show that this individual likely
      survived several years following the injury. The osseous features we describe
      (remodelled bone at the fracture site, asymmetry of entheseal changes likely
      related to the particular walking pattern of the individual) may be useful in
      personal identification of skeletons of legal interest. Regarding the recognition
      of osteoporosis in unearthed skeletons, our study underlines that the cortical
      thickness, microscopic features, degree of crystallinity and Ca/P ratio represent
      more useful elements than the mean bone density, mineral/matrix ratio and mineral
      maturity, which are more sensitive to diagenetic changes that affect the mineral
      phase post-mortem.

PMID- 24308248
TI  - Dirofilaria repens as a cause of subconjunctival infection in a 77-years old
      female patient from Croatia--a case report.
AB  - The zoonotic parasites of the genus Dirofilaria are on the increase as an
      accidental finding or as a cause of disease in humans worldwide. Human
      dirofilariasis usually manifests as either subcutaneous infiltrates or lung
      parenchymal disease, in many cases asymptomatically. We report the case of a 77
      year old female patient presenting with irritation and pain in her left eye.
      Ophthalmologic examination of the temporal part of her left eye revealed motile
      and threadlike organism, which was surgically extracted and morphologically
      identified as Dirofilaria. Further molecular diagnostics with polymerase chain
      reaction (PCR) confirmed that the isolated organism is Dirofilaria repens. Due to
      already recognized autochthonous occurrence of human dirofilariasis in Croatia,
      human dirofilariasis must be included in the differential diagnosis of patients
      presenting with subcutaneous nodules, eye affection and other potential
      manifestations of this disease.

PMID- 24308249
TI  - The weak spots of saliva buffering tests.
AB  - Saliva buffering test is in need of improvements. This article illustrates the
      most commonly used saliva buffering capacity tests and its major problems.
      Starting with Ericsson and his laboratory buffer capacity test and all the way to
      Kitasako a lot of issues are to release. The aim of this paper is to put saliva
      buffering tests up to serious discussion.

PMID- 24308250
TI  - Therapy of umbilical hernia during laparoscopic cholecystectomy.
AB  - The aim of this study is to show our experience with umbilical hernia
      herniorrhaphy and laparoscopic cholecystectomy, both in the same act. During last
      10 years we operated 89 patients with cholecystitis and pre-existing umbilical
      hernia. In 61 of them we performed standard laparoscopic cholecystectomy and
      additional sutures of abdominal wall, and in 28 patients we performed in the same
      act laparoscopic cholecystectomy and herniorrhaphy of umbilical hernia. We
      observed incidence of postoperative herniation, and compared patients recovery
      after herniorrhaphy combined with laparoscopic cholecystectomy in the same act,
      and patients after standard laparoscopic cholecystectomy and additional sutures
      of abdominal wall. Patients, who had in the same time umbilical hernia
      herniorrhaphy and laparoscopic cholecystectomy, shown better postoperative
      recovery and lower incidence of postoperative umbilical hernias then patients
      with standard laparoscopic cholecystectomy and additional abdominal wall sutures.

PMID- 24308251
TI  - Primary malignant fibrous histiocytoma of the spleen: recurrence eight years
      after splenectomy--report of a case and literature review.
AB  - Primary intraabdominal malignant mesenchymal tumors are very rare. There are just
      few cases of intraabdominal visceral malignant fibrous histiocytoma in the
      literature. We report a case of primary malignant fibrous histiocytoma of the
      spleen in a 57-year-old man, with a recurrence eight years after the splenectomy.
      After the initial surgery the patient was without complaints, and refused to
      receive chemotherapy or radiotherapy. Eight years after the surgery the patient
      reported due to general weakness and malaise when the diagnosis of disease
      relapse was established. Radical surgery was performed although the tumor
      involved large curvature of the stomach, left crus of the diaphragm, splenic
      flexure of the colon and tail of pancreas. Four months after the surgery patient
      died. To the best of our knowledge, to date, only 18 cases have been reported in
      the literature, describing malignant fibrous histiocytoma of the spleen.

PMID- 24308252
TI  - Brain tissue adaptability to slow-growing tumors: case report of clivus
      meningioma.
AB  - A 46-year-old female patient with a large slow-growing craniocervical junction
      tumor is presented. Her complaints began 6 months before with sensory and painful
      sensations, sphincter impairment, and motor events (spastic tetraparesis, more
      pronounced on the left extremities). Magnetic resonance of the head revealed a
      rounded tumor of 2.5 cm in diameter, by its characteristics corresponding to
      meningioma, at the level of C1 vertebra and craniocervical junction, with the
      base at spinal canal anterior wall, occupying most of the craniocervical
      junction, compressing spinal cord and medulla oblongata. Intracerebral computed
      tomography angiography showed spared lumen and a satisfactory image of vertebral
      arteries bypassing the expansive growth at the occipital foramen, confirming slow
      tumor growth. Antiedematous therapy led to transient improvement in extremity
      strength and partial recovery of neurologic deficit, which resolved completely
      upon neurosurgical operation and rehabilitation. This case report exemplifies
      brain adaptability to slowly growing expansive neoplasms, based on its volume
      reduction up to the moment when further adaptation is not possible anymore, i.e.
      breaking of the mechanism of adaptation. Because of brain adaptability, such
      slowly growing tumors may stay asymptomatic for a long time. Brain plasticity
      also includes adaptation and autoregulation of the circulation, thus ensuring
      stable blood flow.

PMID- 24308253
TI  - Complex regional pain syndrome type I after diphtheria-tetanus (Di-Te)
      vaccination.
AB  - Complex regional pain syndrome type I (CRPS I) is a disorder of one or more
      extremities characterized by pain, abnormal sensitivity (allodynia), swelling,
      limited range of motion, vasomotor instability, fatigue and emotional distress.
      The symptoms may be aggravated by even minor activity or weather change. It is
      usually provoked by injury, surgery or injection but in a small proportion of
      patients CRPS I develops without a clear causative event. There are several
      literature reports on CRPS after rubella and hepatitis B vaccination. We present
      a case of CRPS I affecting the left arm after diphtheria and tetanus (Di-Te)
      vaccination in the left deltoid muscle in a young girl having experienced
      profound emotional stress before the vaccination procedure. History data on
      previous minor trauma at the site of vaccination or emotional stress may
      necessitate temporary vaccination delay due to their proneness to impaired local
      or systemic immune response and CRPS as a complication of vaccination. If a child
      or an adult has prominent swelling and severe pain after vaccination, the
      diagnosis of CRPS I should be considered and if confirmed, the multidisciplinary
      treatment should start as soon as possible.

PMID- 24308254
TI  - Biomedical psychiatry and its concealed metaphors: an anthropological
      perspective.
AB  - The idea that power relations structure social life is self-evident to most
      anthropologists. Western medical knowledge or biomedicine, and by extension
      science or scientific knowledge, however, has until relatively recently been
      exempt from anthropological scrutiny in political terms. An understanding of
      biomedicine as a system of knowledge that is not a copy of facts but a
      representation of them has entailed a break with the traditional separation of
      folk knowledge and scientific knowledge in anthropology, making it possible to
      include biomedicine in the repertoire of ethnographic objects. The peculiarity of
      biomedicine as a cultural system, seen from this perspective, lies in a paradox:
      its self-characterization as a set of non-ideological discourses and practices is
      a representation that conceals its ideological and power-saturated nature.
      Through an analysis of DSM-IV-TR, this article explores some of the
      representational strategies through which this concealment takes place in
      biomedical psychiatry: the asocial and universal character of mental illness
      categories; the neutrality of clinical practice; and the non-moral nature of
      clinical criteria and judgment. These are concealed metaphors in the true sense,
      for not only do they speak of something without naming it but they also deny
      their own existence as metaphors.

PMID- 24308255
TI  - Sex steroids: beyond conventional dimorphism.
AB  - Sexual dimorphism is a characteristic of a large number of species, ranging from
      lower invertebrates to mammals and, last but not least, humans. Recognition of
      the various factors regulating sexual dimorphism initial establishment (i.e. sex
      determination and differentiation) and subsequent life-long adaptation to
      distinct functional and behavioural patterns has remained a hot topic for several
      decades. As our understanding of the various molecular pathways involved in this
      process increases, the significant role of sex steroids becomes more evident. At
      the same time, the recognition of new sites of steroid production (e.g. parts of
      the brain) and aromatization, as well as new target cells (owing to the proposed
      presence of additional receptors to those classically considered as primary
      steroid receptors) has lead to the need to revisit their spectrum of actions
      within a novel, multifactorial context. Thus, anthropology and medicine are
      presented with the challenge to unravel a major mystery, i.e. that of sexual
      orientation and differentiation and its potential contribution in human evolution
      and civilization development, taking advantage of the high-tech research tools
      provided by modern biotechnology. This short review summarizes the basic
      principles of sex determination and sex steroid function as they have been
      classically described in the literature and then proceeds to present examples of
      how modern research methods have started to offer a new insight on the more
      subtle details of this process, stressing that it is extending to virtually every
      single part and system of the body.

PMID- 24308256
TI  - Who is the patient? Disclosure of information and consent in anesthesia and
      intensive care (informed consent).
AB  - Physicians have always strived to uphold all the ethical postulates of the
      medical profession in all aspects of the practice, however with the vast advances
      in science and technology, numerous ethical dilemmas regarding all aspects of
      life and ultimately death have emerged. Medical decisions however, are no longer
      in the sole jurisdiction of traditional Hippocratic medicine but are now
      deliberated and delivered by the patient and they are comprised of a number of
      additional determining aspects such as psychological, social, legal, religious,
      esthetic, administrative etc., which all together represent the complete best
      interest of the patient. This is the basic goal of the "Informed Consent". The
      widening of legal boundaries regarding professional liability may consequentially
      lead to a "defensive medicine" and a deterioration in the quality of healthcare.
      In the Republic of Croatia there a four types of liability and the
      hyperproduction of laws which regulate healthcare geometrically increase the
      hazards to which physicians are exposed to on a daily basis. When evaluating the
      Croatian informed consent for anesthesia, we can come to the conclusion that it
      is completely impractical and as such entirely unnecessary. Anesthesiologists
      should concentrate on an informed consent which would in brief explain all the
      necessary information a "reasonable" anesthesiologist would disclose to a
      "reasonable" patient so that a patient could undertake a diagnostic or
      therapeutic procedure unburdened and with complete confidence in the physicians
      who are involved in the treatment of the respective patient.

PMID- 24308257
TI  - Pharmacotherapy of suicidal behaviour in major depression, schizophrenia and
      bipolar disorder.
AB  - The psychopathological dynamics in suicidality overcomes actual diagnostic
      distribution therefore pharmacotherapy has restricted role in overall prevention
      of suicidal behaviour among mentally ill and is demanding for clinician. This
      role is achieved through reduction and alleviation of suicidal risk with rational
      and individual pharmacotherapeutic approach emphasising effective, safe and
      tolerable treatment. The genetic and epigenetic factors, dysfunction of
      neurotransmitter, neuroendocrine system and stress response system has been
      determining for neurobiology of suicidality. Therefore, pharmacotherapeutic
      approach should be focused, not only on prevention and reduction of suicidality,
      but adjusted for general and diagnosis-specific risk factors. Suicidality
      represents trans-diagnostic issue, however making the correct diagnosis is of
      great importance. Identical group of psychiatric medications or even the same
      drug, could be palliating for suicidal behaviour in one diagnostic category and
      in other aggravating concerning suicidal ideations. Clinician should be reserved
      towards epidemiological studies about reducing suicidal rate due to increased
      consumption of antidepressants. Detailed data analysis showed there is no
      relevancy which antidepressants were given to specific patient, in what age and
      phase of illness. The FDA has issued warnings about possible increased risk of
      suicidal behaviour in children and adolescents when given antidepressant therapy.
      In general, serotoninergic drugs have neutral or mildly protective effect on
      potential suicidal behaviour while noradrenergic drugs may have activating effect
      or could even worsen suicidal ideation in certain phase of the illness. When
      given in appropriate dose and the right time, dual or noradrenergic
      antidepressants, could also have good protective impact on specific patient. In
      patients with bipolar disorder, antidepressive drug could be trigger for suicidal
      behaviour. Greater susceptibility when diagnosing bipolar disorder and broader
      usage of mood stablizing medications, alone or combined with other
      psychopharmacotherapy, has the significant role in suppression and elimination of
      suicidal behaviour. The lithium and sodium valproate are found to be particularly
      suitable for prevention and elimination of suicidal behaviour along with some
      other mood stabilizers. Pharmacotherapy of suicidality in patients with
      schizophrenia represents specific problem. Confirmed drug with anti-suicidal
      effect, clozapine, is not first choice medication and does not represent general
      solution for suicidality in schizophrenia. For clinician, the pharmacotherapy of
      suicidal behaviour consists of skilled individual and rational drug
      administration accompanied with appropriate psychotherapeutic support.

PMID- 24308258
TI  - [A researcher's itinary on the history of the body].
AB  - As a pioneer of a new field of research, history of the body, Georges Vigarello
      goes back over his career as a historian, not so much in search of a hypothetical
      or ultimate unity of the body, but beyond the original dipersion is rather aiming
      at relating the existence of coherences and unified logics passing through
      different fields: the body as an object of thought, of representations and
      practices. In such a perspective, the history of the body sheds light on a
      specific era, underlines its culture, while indicating its possible homogeneity.

PMID- 24308259
TI  - The origins of British sports medicine, 1850-1914.
AB  - This article, by focussing on athletes' training methods and treatments for
      sporting injuries, examines the origins of sports medicine in Britain from around
      1850 to 1914. Although, the phrase 'sports medicine' had not yet been invented,
      the article explains how the development of sports medicine during this period
      was shaped by a wider historical context. Difficulties over defining sports
      medicine, for example, stemmed from its status as a holistic practice in an
      increasingly professionalised medical world. Moreover, ideas concerning the
      training of athletes reflected both contemporary shifts in medical thinking,
      especially physiology, and a power struggle between orthodox and unorthodox
      medical practitioners. During this period, an increasingly competitive sporting
      world, also gave rise to the sporting injury and the need for specialised
      treatments. However, rather these treatments further mirrored contemporary
      medical practices.

PMID- 24308260
TI  - [Beginning of the institutionalization of physical therapy in a Swiss canton:
      1928-1945].
AB  - The institutionalization of physical therapy in Switzerland took place in the
      inter-war period. This article aims to relate the initiation of this process in
      the Canton of Vaud, as a specific example that will nevertheless be compared with
      the Swiss and international contexts. This story occurs around three major events
      between 1928 and 1945: the massage becomes a regulated profession, followed by
      the emergence of a professional association and a specialized school. The
      intention is first to identify the social actors, then the interests, issues, and
      interactions that have contributed to model the modern physical therapy. Finally,
      the techniques used by the masseurs--the first professional physical therapists-
      and their working environment are evoked.

PMID- 24308261
TI  - [Sauveur-Henri-Victor Bouvier (1799-1877): orthopaedist, surgeon and promoter of
      physical education].
AB  - This article establishes the biography of a little known physician of the 19th
      century., whose commitment with orthopaedics and formulation of medical
      gymnastics was important: the surgeon-orthopaedist Sauveur-Henri-Victor Bouvier.
      Several constitutive processes of the medical field of the 19th century are
      analysed: specialization (around orthopaedics), professionalization and
      development of various therapeutic and hygienic methods (among them medical
      gymnastics). Bouvier's biography is particularly instructive and sheds new light
      on these different processes, as well as on the institutionalization of
      orthopaedics from the 1820's up to the 1870's, at the intersection between
      medical and educative fields, between hospital, medical faculty and teaching of
      gymnastics.

PMID- 24308262
TI  - [Scoliotic young girls and orthopaedics in Belle Epoque: the urban surge of
      mecanotherapy in Lausanne and Geneva].
AB  - In Belle Epoque towns marked by the industrial and medical surge, a new technical
      therapy, called mechanotherapy, emerged, stemming from Swedish medical gymnastics
      and auxiliary to orthopaedics. Aiming mostly at treating scoliosis, this therapy
      by movement attracted a sizeable female clientele to these towns, because of the
      hygienic and social conceptions feeding collective imagination linked to the
      bodies of scoliotic young girls. Taking the French-speaking Swiss towns of
      Lausanne and Geneva as examples, the article first seeks to describe the
      emergence of mechanotherapy as a medical and urban phenomenon. It then addresses
      the role played by scoliosis in this orthopaedic practice, and examines the
      clientele attracted to the towns, among which well-born young girls seem to be
      predominant.

PMID- 24308263
TI  - [Transformations of the relationships between medicine and physical activities
      from the beginning of the 19th C. to the beginning of the 20th C. in France].
AB  - In order to understand the modes of cooperation that are practically working
      between two groups with uneven social status, physicians and physical educators,
      since the beginning of the 19th century until the beginning of the 20th century,
      we consider the results of researches that have been realized since three
      decennials. The evolution of those relationships accomplishes itself while the
      definition of respective roles (physician hygienist, physical educator with
      sanitary conception) and the reciprocal adjustment of specialities are becoming
      more precise. The process is tight, and the adaptations of the respective tasks
      are continuously retranslated in terms of statuary dimensions and protection of
      respective jurisdictions of both groups in the process of professionalization.

PMID- 24308264
TI  - [Women's physical and sporting activities in the beginning of the 20th C.: a
      technical way maintaining a normative definition of the body, the example of
      menstruation].
AB  - End of the 19th century France is characterized by a wave of hygiene campaigns
      corresponding to a dominant depopulation phenomenon. It is in this context that a
      law is introduced in 1880 which stipulates that gymnastics should be taught in
      all boy's schools: the "loi George", whose provisions are soon extended to girls.
      Female physical and sports practice is thus structured politically and
      scientifically as a project of quantitative and qualitative regeneration of
      "race", based on the Lamarckian idea according to which health and physical
      improvement of the individual is transmitted to their descendants. This paper
      describes the socio-historical conditions of the construction of medical
      discourses about female physical and sports practice as well as their plurality
      and foundation, from 1880 to 1920, when the First Medical Congress on child and
      female Physical Education took place. Ambiguities, tensions, and contradictions
      of the politics of health and regeneration of the female body through physical
      and sports practice are analyzed.

PMID- 24308265
TI  - Laughter in popular games and in sport. The other health of human play.
AB  - Hurling in Cornwall, la soule in Britanny, Shrovetide football in England:
      Popular games have normally been treated as forerunners of modern sport, sport
      having regulated the space and the time of the game, the (non-) violence of
      behaviour, the control of results, the planning, strategy, tactics, techniques
      and evaluation of the competitive action. This is told as a story of social
      improvement and progress--and about turning unhealthy wildness into civilized
      'healthy' sport activity. What sociological analysis of game-playing tended to
      ignore was the laughter of the participants. With the seriousness of modern
      sport, as it was established in the nineteenth century, a culture of laughter
      disappeared. This study tries to counter this mainstream by a phenomenology of
      laughter in popular games. A contrasting attention is turned towards the
      seriousness of sporting competition, the smile in modern sport and fitness, and
      the 'underground' dimension of laughter in modern sports. By comparative
      analysis, laughter reveals as a bodily discourse about the imperfect human being.
      It tells an oppositional story about the perfectionism in the order of Western
      thinking--in sports as well as in health. The bodily 'physiology' of laughter,
      the exploding psychical energy, and the inter-bodily social relations in laughter
      and play and game point towards the multi-dimensionality of health, as it was
      formulated by WHO: as "physical, mental, and social well-being".

PMID- 24308266
TI  - [Between hygiene, therapeutics and education of the body (France, Germany,
      England): European histories of a specialization?].

PMID- 24308269
TI  - Part-set cuing of texts, scenes, and matrices.
AB  - In four experiments, we extended the study of part-set cuing to expository texts
      and pictorial scenes. In Experiment 1, recall of expository text was tested with
      and without part-set cues in the same order as the original text; cues strongly
      impaired recall. Experiment 2 repeated Experiment 1 but used cues in random order
      and found significant but reduced impairment with cuing. Experiments 3 and 4
      examined the part-set cuing of objects presented in a scene or matrix and found
      virtually no effect of cuing. More objects were recalled from the scene than from
      the matrix, indicating that the scene's organization aided memory, but the cues
      did not assist recall. These results extend the domains in which part-set cues
      have either impaired or failed to improve recall. Implications for education and
      eyewitness accounts are briefly considered. 

PMID- 24308268
TI  - The conformation of lipid-free human apolipoprotein A-I in solution.
AB  - Apolipoprotein AI (apoA-I) is the principal acceptor of lipids from ATP-binding
      cassette transporter A1, a process that yields nascent high density lipoproteins.
      Analysis of lipidated apoA-I conformation yields a belt or twisted belt in which
      two strands of apoA-I lie antiparallel to one another. In contrast, biophysical
      studies have suggested that a part of lipid-free apoA-I was arranged in a four
      helix bundle. To understand how lipid-free apoA-I opens from a bundle to a belt
      while accepting lipid it was necessary to have a more refined model for the
      conformation of lipid-free apoA-I. This study reports the conformation of lipid
      free human apoA-I using lysine-to-lysine chemical cross-linking in conjunction
      with disulfide cross-linking achieved using selective cysteine mutations. After
      proteolysis, cross-linked peptides were verified by sequencing using tandem mass
      spectrometry. The resulting structure is compact with roughly four helical
      regions, amino acids 44-186, bundled together. C- and N-terminal ends, amino
      acids 1-43 and 187-243, respectively, are folded such that they lie close to one
      another. An unusual feature of the molecule is the high degree of connectivity of
      lysine40 with six other lysines, lysines that are close, for example, lysine59,
      to distant lysines, for example, lysine239, that are at the opposite end of the
      primary sequence. These results are compared and contrasted with other reported
      conformations for lipid-free human apoA-I and an NMR study of mouse apoA-I. 

PMID- 24308270
TI  - Efficient "light-soaking"-free inverted organic solar cells with aqueous solution
      processed low-temperature ZnO electron extraction layers.
AB  - Low-temperature processes are unremittingly pursued in the fabrication of organic
      solar cells. The paper reports that the highly efficient and "light-soaking"-free
      inverted organic solar cell can be achieved by using ZnO thin films processed
      from the aqueous solution method at a low temperature. The inverted organic solar
      with an aqueous-processed ZnO thin film annealed at 150  degrees C shows an
      efficiency of 3.79%. Even when annealed at a temperature as low as 80  degrees C,
      the device still shows an efficiency of 3.71%. With the proper annealing
      temperature of 80  degrees C, the flexible device, which shows an efficiency of
      3.56%, is fabricated on PET. This flexible device still keeps the efficiency
      above 3.40% after bent for 1000 times with a curvature radius of 50 mm. In
      contrast, a low annealing temperature leads to an inferior device performance
      when the ZnO thin film is processed from the widely used sol-gel method. The
      device with sol-gel processed ZnO annealed at 150  degrees C only shows a PCE of
      1.3%. Furthermore, the device shows a strong "light-soaking" effect, which is not
      observed in the device containing an aqueous-processed ZnO thin film. Our results
      suggest that the adopted aqueous solution method is a more efficient low
      temperature technique, compared with the sol-gel method. 

PMID- 24308267
TI  - Cell surface self-assembly of hybrid nanoconjugates via oligonucleotide
      hybridization induces apoptosis.
AB  - Hybrid nanomaterials composed of synthetic and biological building blocks possess
      high potential for the design of nanomedicines. The use of self-assembling
      nanomaterials as "bio-mimics" may trigger cellular events and result in new
      therapeutic effects. Motivated by this rationale, we designed a therapeutic
      platform that mimics the mechanism of immune effector cells to cross-link surface
      receptors of target cells and induce apoptosis. This platform was tested against
      B-cell lymphomas that highly express the surface antigen CD20. Here, two
      nanoconjugates were synthesized: (1) an anti-CD20 Fab' fragment covalently linked
      to a single-stranded morpholino oligonucleotide (MORF1), and (2) a linear polymer
      of N-(2-hydroxypropyl)methacrylamide (HPMA) grafted with multiple copies of the
      complementary oligonucleotide MORF2. We show that the two conjugates self
      assemble via MORF1-MORF2 hybridization at the surface of CD20(+) malignant B
      cells, which cross-links CD20 antigens and initiates apoptosis. When tested in a
      murine model of human non-Hodgkin's lymphoma, the two conjugates, either
      administered consecutively or as a premixture, eradicated cancer cells and
      produced long-term survivors. The designed therapeutics contains no small
      molecule cytotoxic compounds and is immune-independent, aiming to improve over
      chemotherapy, radiotherapy and immunotherapy. This therapeutic platform can be
      applied to cross-link any noninternalizing receptor and potentially treat other
      diseases. 

PMID- 24308271
TI  - Fuse or die: how to survive the loss of Dam in Vibrio cholerae.
AB  - Dam methylates GATC sequences in gamma-proteobacteria genomes, regulating several
      cellular functions including replication. In Vibrio cholerae, which has two
      chromosomes, Dam is essential for viability, owing to its role in chr2
      replication initiation. In this study, we isolated spontaneous mutants of V.
      cholerae that were able to survive the deletion of dam. In these mutants,
      homologous recombination and chromosome dimer resolution are essential, unless
      DNA mismatch repair is inactivated. Furthermore, the initiator of chr2
      replication, RctB, is no longer required. We show that, instead, replication of
      chr2 is insured by spontaneous fusion with chr1 and piggybacking its replication
      machinery. We report that natural fusion of chr1 and chr2 occurred by two
      distinct recombination pathways: homologous recombination between repeated IS
      elements and site-specific recombination between dif sites. Lastly, we observed a
      preferential fusion of the two chromosomes in their terminus of replication.

PMID- 24308272
TI  - Sexual disclosures: connections to relational satisfaction and closeness.
AB  - This study examines sexual communication by describing the content of sexual
      disclosures within marital relationships and assessing the association between
      sexual disclosures and relational outcomes, specifically relational satisfaction
      and closeness. A survey administered to 293 married individuals (58% female) who
      had an average age of 40 years (range = 20-73), 13.7 years of marriage (range = 1
      month to 54 years), and who reported high levels of relational satisfaction
      assessed the relation between the content of sexual disclosures and satisfaction
      and closeness. While sexual disclosures are made infrequently, positive affect
      and sexual preferences are disclosed more than negative topics and disclosing
      sexual information is positively related to relationship satisfaction, rrho(280)
      =.26, p <.001; and closeness, rs(280) =.475, p <.01. Therapists can use these
      findings to show clients the positive relation between revealing sexual
      information and relationship satisfaction and closeness, as reported by
      individuals experiencing relationship satisfaction. 

PMID- 24308273
TI  - Enzyme-directed assembly of nanoparticles in tumors monitored by in vivo whole
      animal imaging and ex vivo super-resolution fluorescence imaging.
AB  - Matrix metalloproteinase enzymes, overexpressed in HT-1080 human fibrocarcinoma
      tumors, were used to guide the accumulation and retention of an enzyme-responsive
      nanoparticle in a xenograft mouse model. The nanoparticles were prepared as
      micelles from amphiphilic block copolymers bearing a simple hydrophobic block and
      a hydrophilic peptide brush. The polymers were end-labeled with Alexa Fluor 647
      dyes leading to the formation of labeled micelles upon dialysis of the polymers
      from DMSO/DMF to aqueous buffer. This dye-labeling strategy allowed the presence
      of the retained material to be visualized via whole animal imaging in vivo and in
      ex vivo organ analysis following intratumoral injection into HT-1080 xenograft
      tumors. We propose that the material is retained by virtue of an enzyme-induced
      accumulation process whereby particles change morphology from 20 nm spherical
      micelles to micrometer-scale aggregates, kinetically trapping them within the
      tumor. This hypothesis is tested here via an unprecedented super-resolution
      fluorescence analysis of ex vivo tissue slices confirming a particle size
      increase occurs concomitantly with extended retention of responsive particles
      compared to unresponsive controls. 

PMID- 24308274
TI  - Vegetable, fruit and nitrate intake in relation to the risk of Barrett's
      oesophagus in a large Dutch cohort.
AB  - There are few epidemiological data on the dietary risk factors of Barrett's
      oesophagus, a precursor of oesophageal adenocarcinoma. The present study
      investigated the association between vegetable, fruit and nitrate intake and
      Barrett's oesophagus risk in a large prospective cohort. The Netherlands Cohort
      Study recruited 120,852 individuals aged 55-69 years in 1986. Vegetable and fruit
      intake was assessed using a 150-item FFQ, and nitrate intake from dietary sources
      and drinking water was determined. After 16.3 years of follow-up, 433 cases (241
      men and 192 women) of Barrett's oesophagus with specialised intestinal metaplasia
      and 3717 subcohort members were analysed in a case-cohort design using Cox
      proportional hazards models while adjusting for potential confounders. Men
      exhibited a lower risk of Barrett's oesophagus in the highest v. the lowest
      quintile of total (multivariable-adjusted hazard ratio (HR): 0.66, 95% CI 0.43,
      1.01), raw (HR 0.63, 95% CI 0.40, 0.99), raw leafy (HR 0.55, 95% CI 0.36, 0.86)
      and Brassica (HR 0.64, 95% CI 0.41, 1.00) vegetable intake. No association was
      found for other vegetable groups and fruits. No significant associations were
      found between vegetable and fruit intake and Barrett's oesophagus risk among
      women. Total nitrate intake was inversely associated with Barrett's disease risk
      in men (HR 0.50, 95% CI 0.25, 0.99) and positively associated with it in women
      (HR 3.77, 95% CI 1.68, 8.45) (P for interaction = 0.04). These results suggest
      that vegetable intake may contribute to the prevention of Barrett's oesophagus.
      The possible differential effect in men and women should be evaluated further.

PMID- 24308275
TI  - The relationship between neurotrophins and bipolar disorder.
AB  - Relationship between neurotrophins, especially brain-derived neurotrophic factor
      (BDNF) and bipolar disorder (BPD) has been widely investigated, but results have
      been inconsistent. BDNF polymorphism may be associated with the susceptibility to
      subtype BPD such as rapid cycling BPD or early onset BPD. Met allele carriers of
      Val66Met of BDNF gene had smaller gray matter (GM) in both patients and healthy
      controls, but bipolar patients carrying Met allele had better response to lithium
      treatment. Decreased serum/plasma BDNF levels were observed at different mood
      states. BDNF may interact with other systems to execute its neuroprotective
      effects. Overall data suggest that neurotrophins may be involved in the
      pathogenesis of BPD and treatment response, but the magnitude of their role needs
      further investigation with large sample size studies. 

PMID- 24308276
TI  - Options to enhance recovery from aphasia by means of non-invasive brain
      stimulation and action observation therapy.
AB  - Aphasia is a highly disabling language disorder usually caused by a left
      lateralized brain damage. Even if traditional linguistic-based therapies have
      been proved to induce an adequate clinical improvement, a large percentage of
      patients are left with some degree of language impairments. Therefore, new
      approaches to common speech therapies are urgently needed in order to maximize
      the recovery from aphasia. The recent application of non-invasive
      neurostimulation techniques to language rehabilitation has already provided
      promising results particularly for the recovery of word-retrieval deficits in
      chronic stroke aphasic patients. Positive outcomes also come from action
      observation therapy. Indeed, some very recent studies have shown that the
      observation and/or execution of gestures positively influences language recovery
      especially for words related to human actions. This article gives an overview of
      the most important results achieved using these two approaches and discusses how
      the application of these treatments might potentiate aphasia recovery. 

PMID- 24308277
TI  - Pharmacotherapy of generalized anxiety disorder: focus and update on pregabalin.
AB  - Generalized anxiety disorder (GAD) is one of the most common psychiatric
      disorders and clinically characterized by both psychological anxiety and somatic
      symptoms (muscular tension and autonomic symptoms). Next to serotonergic
      antidepressants, the Ca(2+) channel alpha2delta ligand pregabalin is an approved
      first-line treatment of GAD in many countries. Pregabalin is considered effective
      against psychological and somatic anxiety symptoms alike. However, occurrence of
      discontinuation syndromes and a growing number of reports regarding abuse or
      dependence during the last years are concerns, particularly in patients with a
      history of addictive behavior. Here we review key issues of GAD and the
      pharmacology and pharmacokinetics of pregabalin. Above all, we evaluate evidence
      from available randomized placebo-controlled as well as head-to-head clinical
      trials with other drugs regarding its efficacy and safety in the GAD treatment. 

PMID- 24308278
TI  - Recognition, diagnosis and treatment of postpartum bipolar depression.
AB  - Bipolar disorder is a serious and often chronic disorder characterized by
      episodes of depression, hypomania, mania or mixed states that affects many
      individuals worldwide, and is a leading cause of years of 'healthy' life lost as
      a result of disability and premature mortality. For women, bipolar disorder tends
      to cluster during the childbearing years. Detection of bipolar disorder can be
      complicated and therefore it is essential that women presenting with mood
      episodes after childbirth receive a comprehensive examination to allow for
      accurate diagnosis, with particular attention to manic symptoms. Once a diagnosis
      of bipolar disorder is confirmed, pharmacotherapy with consideration made to
      breastfeeding status may be considered alone or in combination with
      psychotherapy. 

PMID- 24308279
TI  - Pramipexole augmentation in treatment-resistant major depressive disorder.
AB  - Evaluation of: Cusin C, Iovieno N, Iosifescu DV et al. A randomized, double
      blind, placebo-controlled trial of pramipexole augmentation in treatment
      resistant major depressive disorder. J. Clin. Psychiatry 74(7), e636-e641 (2013).
      To overcome limited efficacy in antidepressants, clinicians may choose
      augmentation, switching to a different antidepressant, or a combination of
      different antidepressant drugs based on the individual patient's clinical
      circumstances. Among such options for difficult-to-treat major depressive
      disorder (MDD) patients, augmentation therapy with atypical antipsychotics,
      psychostimulants, dopamine agonists, serotonin 1A partial agonists, lithium, and
      thyroid hormones are commonly used in clinical practice. In fact, augmentation
      therapy has some clinical merits and is more convenient than switching
      medications and combination approaches for treating MDD. One such augmentation
      agent, pramipexole has been proposed, and has been implicated in the development
      and treatment of MDD. Recently, randomized controlled trials with pramipexole
      augmentation have been conducted and have demonstrated that pramipexole is a safe
      and potentially efficacious augmentation strategy. This article will discuss
      currently available clinical trial data and the potential role of pramipexole in
      MDD treatment, including clinical significance, limitations, and future research
      directions. 

PMID- 24308280
TI  - Therapeutic options for cervicogenic headache.
AB  - The term cervicogenic headache (CeH) describes a syndrome originating from the
      cervical spine. There are a variety of therapeutic approaches used for the
      management of CeH, but scientific evidence of their effectiveness is scarce. No
      medication drug has proven to be effective. The evidence for greater occipital
      nerve blocks, cervical nerve blockades, facet joint injections and surgical
      procedures is limited. Several physical therapy interventions are proposed for
      CeH, with spinal manipulation and soft tissue interventions being the most
      commonly used. However, the lack of solid evidence of positive effects and risks
      of serious complications for spinal manipulation should be considered in favor of
      other physical therapy interventions associated with less risk. The inconsistent
      results in the literature can be related to the fact that maybe not all
      therapeutic interventions are appropriate for all patients with CeH or maybe not
      all patients with CeH will benefit from particular interventions. 

PMID- 24308281
TI  - Current and future treatment modalities in schizophrenia: novel antipsychotic
      drugs and cognitive therapy.
AB  - In 60 years of use of antipsychotic drugs in schizophrenia, the only definite
      advance has been the introduction of clozapine. Some but not all other atypical
      or second-generation drugs may have small therapeutic advantages over
      conventional antipsychotics, but this remains controversial. New entrant
      atypicals seem unlikely to be therapeutically superior to conventional drugs, and
      glutamatergic drugs have yet to fulfill their theoretical promise. There is
      considerable current interest in novel mechanisms of antipsychotic action, but no
      such drugs have yet reached market authorization. A psychotherapeutic
      intervention, cognitive behavioral therapy has also found a place in the
      treatment of schizophrenia. However, the size of its effect against psychotic
      symptoms is small, and current evidence suggests no effect against negative
      symptoms or in reducing relapse. 

PMID- 24308282
TI  - A tailored implementation intervention to implement recommendations addressing
      polypharmacy in multimorbid patients: study protocol of a cluster randomized
      controlled trial.
AB  - BACKGROUND: Multimorbid patients frequently receive complex medication regimens
      and are at higher risk for adverse drug reactions and hospitalisations. Managing
      patients with polypharmacy is demanding, because it requires coordination of
      multiple prescribers and intensive monitoring. Three evidence-based
      recommendations addressing polypharmacy in primary care are structured medication
      counselling, use of medication lists and medication reviews to avoid potentially
      inappropriate medication (PIM). Although promising to improve patient outcomes,
      these recommendations are not well implemented in German routine care.
      Implementation of guidelines is often hindered by specific "determinants of
      change". "Tailored" interventions are designed to specifically address previously
      identified determinants. This study examines a tailored intervention to implement
      the aforementioned recommendations into German primary care practices. This study
      is part of the European Tailored Interventions for Chronic Diseases project,
      which aims at contributing knowledge about the methods used for tailoring.
      METHODS/DESIGN: The study is designed as a cluster randomized controlled trial
      with primary care practices of general practitioners (GPs) who are organized in
      quality circles. Quality circles will be the unit of randomization with a 1:1
      ratio. Follow-up time is 6 months. GPs and healthcare assistants in the
      intervention group will receive training on medication management. Each GP will
      create a tailored concept of how to implement the three recommendations into
      his/her practice. Evidence-based checklists for medication counselling and
      medication reviews will be provided for physicians. A tablet PC with an
      interactive educational tool and information leaflets will be provided for use by
      patients to inform about the necessity of continuous medication management.
      Control practices will not receive special training and will provide care as
      usual. Primary outcome is the degree of implementation of the three
      recommendations, which will be measured using a prespecified set of indicators.
      Additionally, the PIM prescription rate, patient activation, patients' beliefs
      about medicine, medication adherence and patients' social support will be
      measured. DISCUSSION: This study will contribute knowledge about the feasibility
      of implementing recommendations for managing patients with polypharmacy in
      primary care practices. Additionally, this study will contribute knowledge about
      methods for tailoring of implementation interventions. TRIAL REGISTRATION:
      Clinicaltrials.gov ISRCTN34664024.

PMID- 24308283
TI  - Palladium-catalyzed synthesis of 2-(aminomethyl)indoles from 3-(o
      trifluoroacetamidoaryl)-1-propargylic alcohols and amines.
AB  - A novel palladium-catalyzed approach to 2-(aminomethyl)indoles from 3-(o
      trifluoroacetamidoaryl)-1-propargylic alcohols and amines has been developed. 

PMID- 24308284
TI  - Viral quasispecies inference from 454 pyrosequencing.
AB  - BACKGROUND: Many potentially life-threatening infectious viruses are highly
      mutable in nature. Characterizing the fittest variants within a quasispecies from
      infected patients is expected to allow unprecedented opportunities to investigate
      the relationship between quasispecies diversity and disease epidemiology. The
      advent of next-generation sequencing technologies has allowed the study of virus
      diversity with high-throughput sequencing, although these methods come with
      higher rates of errors which can artificially increase diversity. RESULTS: Here
      we introduce a novel computational approach that incorporates base quality scores
      from next-generation sequencers for reconstructing viral genome sequences that
      simultaneously infers the number of variants within a quasispecies that are
      present. Comparisons on simulated and clinical data on dengue virus suggest that
      the novel approach provides a more accurate inference of the underlying number of
      variants within the quasispecies, which is vital for clinical efforts in mapping
      the within-host viral diversity. Sequence alignments generated by our approach
      are also found to exhibit lower rates of error. CONCLUSIONS: The ability to infer
      the viral quasispecies colony that is present within a human host provides the
      potential for a more accurate classification of the viral phenotype.
      Understanding the genomics of viruses will be relevant not just to studying how
      to control or even eradicate these viral infectious diseases, but also in
      learning about the innate protection in the human host against the viruses.

PMID- 24308285
TI  - Mussel-inspired thermosensitive polydopamine-graft-poly(N-isopropylacrylamide)
      coating for controlled-release fertilizer.
AB  - A thermoresponsive release multi-element compound fertilizer was first reported
      on the basis of a polydopamine-graft-poly(N-isopropylacrylamide) bilayer coated
      on a salty core by a combination of dopamine chemistry and surface-initiated atom
      transfer radical polymerization techniques, and the control of nutrient release
      in response to the environmental temperature was investigated. The successful
      synthesized stimuli-responsive fertilizers were confirmed by transmission
      electron microscopy (TEM), Fourier transforms infrared spectroscopy (FTIR),
      thermogravimetric analysis (TGA) and gel permeation chromatography (GPC). The
      release of elements from fertilizer was determined by an inductively coupled
      plasma (ICP) emission spectrometer. The thermosensitive fertilizers exhibit
      outstanding stimuli-responsive permeability to encapsulated nutrients, and the
      release rate of coated elements can be tailored by the ambient temperature. They
      can release nutrients easily at T < lower critical solution temperature (LCST)
      but slow at T > LCST. This strategy of grafting thermoresponsive polymer brushes
      on polydopamine (Pdop)-coated substrates is useful to prepare a stimuli
      responsive release system, which can adjust the release rate according to
      different conditions, and will be effective and promising in the research and
      development of a stimuli-sensitive controlled-release system. 

PMID- 24308286
TI  - Near-edge X-ray absorption fine structure studies of electrospun
      poly(dimethylsiloxane)/poly(methyl methacrylate)/multiwall carbon nanotube
      composites.
AB  - This work describes the near conduction band edge structure of electrospun mats
      of multiwalled carbon nanotube (MWCNT)-polydimethylsiloxane-poly(methyl
      methacrylate) by near edge X-ray absorption fine structure (NEXAFS) spectroscopy.
      Effects of adding nanofillers of different sizes were addressed. Despite observed
      morphological variations and inhomogeneous carbon nanotube distribution, spun
      mats appeared homogeneous under NEXAFS analysis. Spectra revealed differences in
      emissions from glancing and normal spectra, which may evidence phase separation
      within the bulk of the micrometer-size fibers. Further, dichroic ratios show
      polymer chains did not align, even in the presence of nanofillers. Addition of
      nanofillers affected emissions in the C-H, C?O, and C-C regimes, suggesting their
      involvement in interfacial matrix-carbon nanotube bonding. Spectral differences
      at glancing angles between pristine and composite mats suggest that geometric
      conformational configurations are taking place between polymeric chains and
      carbon nanotubes. These differences appear to be carbon nanotube-dimension
      dependent and are promoted upon room temperature mixing and shear flow during
      electrospinning. CH-pi bonding between polymer chains and graphitic walls, as
      well as H-bonds between impurities in the as-grown MWCNTs and polymer pendant
      groups are proposed bonding mechanisms promoting matrix conformation. 

PMID- 24308287
TI  - Synthesis of sulfones from organozinc reagents, DABSO, and alkyl halides.
AB  - Organozinc reagents react with the SO2 surrogate DABSO, and the resulting zinc
      sulfinate salts are alkylated in situ to afford sulfones. This transformation has
      a broad scope and is compatible with a wide range of structural motifs of
      medicinal chemistry relevance including nitrile, secondary carbamates, and
      nitrogen-containing heterocycles. 

PMID- 24308288
TI  - Predictions of glass transition temperature for hydrogen bonding biomaterials.
AB  - We show that the glass transition of a multitude of mixtures containing hydrogen
      bonding materials correlates strongly with the effective number of hydroxyl
      groups per molecule, which are available for intermolecular hydrogen bonding.
      This correlation is in compliance with the topological constraint theory, wherein
      the intermolecular hydrogen bonds constrain the mobility of the hydrogen bonded
      network. The finding that the glass transition relates to hydrogen bonding rather
      than free volume agrees with our recent finding that there is little difference
      in free volume among carbohydrates and polysaccharides. For binary and ternary
      mixtures of sugars, polyols, or biopolymers with water, our correlation states
      that the glass transition temperature is linear with the inverse of the number of
      effective hydroxyl groups per molecule. Only for dry biopolymer/sugar or
      sugar/polyol mixtures do we find deviations due to nonideal mixing, imposed by
      microheterogeneity. 

PMID- 24308289
TI  - Barriers to and facilitators of nurse-parent interaction intended to promote
      healthy weight gain and prevent childhood obesity at Swedish child health
      centers.
AB  - BACKGROUND: Overweight and obesity in preschool children have increased worldwide
      in the past two to three decades. Child Health Centers provide a key setting for
      monitoring growth in preschool children and preventing childhood obesity.
      METHODS: We conducted semi-structured interviews with 15 nurses working at Child
      Health Centers in southwest Sweden in 2011 and 2012. All interviews were tape
      recorded and transcribed verbatim and imported to QSR N'Vivo 9 software. Data
      were analyzed deductively according to predefined themes using content analysis.
      RESULTS: Findings resulted in 332 codes, 16 subthemes and six main themes. The
      subthemes identified and described barriers and facilitators for the prevention
      of childhood obesity at Child Health Centers. Main themes included assessment of
      child's weight status, the initiative, a sensitive topic, parental responses,
      actions and lifestyle patterns. Although a body mass index (BMI) chart
      facilitated greater recognition of a child's deviant weight status than the
      traditional weight-for-height chart, nurses used it inconsistently. Obesity was a
      sensitive topic. For the most part, nurses initiated discussions of a child's
      overweight or obesity. CONCLUSION: CHCs in Sweden provide a favorable opportunity
      to prevent childhood obesity because of a systematic organization, which by
      default conducts growth measurements at all health visits. The BMI chart yields
      greater recognition of overweight and obesity in children and facilitates
      prevention of obesity. In addition, visualization and explanation of the BMI
      chart helps nurses as they communicate with parents about a child's weight
      status. On the other hand, inconsistent use and lack of quality assurance
      regarding the recommended BMI chart was a barrier to prevention, possibly
      delaying identification of overweight or obesity. Other barriers included
      emotional difficulties in raising the issue of obesity because it was perceived
      as a sensitive topic. Some parents deliberately wanted overweight children, which
      was another specific barrier. Concerned parents who took the initiative or
      responded positively to the information about obesity facilitated prevention
      activities.

PMID- 24308290
TI  - Scrambled self-assembly of bacteriochlorophylls c and e in aqueous Triton X-100
      micelles.
AB  - Bacteriochlorophyll (BChl) e was coassembled with BChl c in Triton X-100 micelles
      in aqueous solutions. The Qy absorption bands of the coaggregates were positioned
      between those of aggregates consisting solely of BChl c or e. The electronic
      absorption spectra of the coaggregates could not be reproduced by linear
      combinations of the spectra of the aggregates consisting solely of each pigment,
      but they were in line with the simulated spectra for the self-aggregates in which
      both BChls were randomly distributed. These suggest that BChls c and e are not
      spatially separated; they are homogenously distributed over the self-aggregates
      to give electronic spectra that are different from those of the aggregate
      consisting solely of each pigment. Deaggregation of the scrambled self-aggregates
      by excess Triton X-100 did not produce any spectral components assigned to an
      aggregate consisting solely of either BChl c or e. Acid-induced decomposition of
      the scrambled aggregates showed different kinetics from those of the aggregates
      consisting solely of each pigment. These also support the homogeneous
      distribution of BChls c and e in the scrambled self-aggregates. These results
      will be useful to investigate the major light-harvesting antenna systems of green
      photosynthetic bacteria that contain two kinds of chlorosomal BChls. 

PMID- 24308291
TI  - Adult neurogenesis and its role in neuropsychiatric disease, brain repair and
      normal brain function.
AB  - Neural stem/progenitor cells (NSPCs) in the mammalian brain retain the ability to
      generate new neurones throughout life in discrete brain regions, through a
      process called adult neurogenesis. Adult neurogenesis, a dramatic form of adult
      brain circuitry plasticity, has been implicated in physiological brain function
      and appears to be of pivotal importance for certain forms of learning and memory.
      In addition, failing or altered neurogenesis has been associated with a variety
      of brain diseases such as major depression, epilepsy and age-related cognitive
      decline. Here we review recent advances in our understanding of the basic biology
      underlying the neurogenic process in the adult brain, focusing on mechanisms that
      regulate quiescence, proliferation and differentiation of NSPCs. In addition, we
      discuss how neurogenesis influences normal brain function, and in particular its
      role in memory formation, as well as its contribution to neuropsychiatric
      diseases. Finally, we evaluate the potential of targeting endogenous NSPCs for
      brain repair. 

PMID- 24308292
TI  - The mild(r) procedure: a systematic review of the current literature.
AB  - OBJECTIVES: This study's objective was to determine if the literature supports
      use of the Minimally Invasive Lumbar Decompression (mild(r)) procedure (Vertos
      Medical, Aliso Viejo, CA, USA) to reduce pain and improve function in patients
      with symptomatic degenerative lumbar spinal stenosis. DESIGN/SETTINGS: The study
      was designed as an evidence-based review of available data. Studies were
      identified from PubMed, Embase, and the Cochrane Library. Articles were evaluated
      using the Grading of Recommendations Assessment, Development and Evaluation
      Working Group system. Results were compiled assessing short- (4-6 weeks), medium-
      (3-6 months), and long-term (>1 year) outcomes. The primary outcomes evaluated
      were pain, measured by the visual analog scale (VAS), and function, measured by
      the Oswestry Disability Index (ODI). Secondary outcomes included pain and patient
      satisfaction, measured by the Zurich Claudication Questionnaire, adverse
      effects/complications, and changes in utilization of co-interventions. RESULTS:
      The literature search revealed one randomized controlled trial (RCT) and 12 other
      studies (seven prospective cohort, four retrospective, and one case series) that
      provided information on the use of mild(r) in patients with degenerative lumbar
      spinal stenosis. All studies showed statistically significant improvements in VAS
      and ODI scores at all time frames compared with preprocedure levels; the RCT
      showed improvement over controls. Categorical data were not provided; thus, the
      proportion of patients who experienced minimal clinically meaningful outcomes is
      unknown. CONCLUSION: The current body of evidence addressing mild(r) is of low
      quality. High-quality studies that are independent of industry funding and
      provide categorical data are needed to clarify the proportions of patients who
      benefit from mild(r) and the degree to which these patients benefit. Additional
      data at up to 2 years are needed to determine the overall utility of the
      procedure.

PMID- 24308293
TI  - New developments in the use of gene therapy to treat Duchenne muscular dystrophy.
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD) is a lethal X-linked inherited
      disorder characterised by progressive muscle weakness, wasting and degeneration.
      Although the gene affected in DMD was identified over 25 years ago, there is
      still no effective treatment. AREAS COVERED: Here we review some of the genetic
      based strategies aimed at amelioration of the DMD phenotype. A number of Phase
      II/III clinical trials of antisense oligonucleotide-induced exon skipping for
      restoration of the open reading frame (ORF) of the DMD gene have recently been
      completed. The potential strategies for overcoming the hurdles that appear to
      prevent exon skipping becoming an effective treatment for DMD currently are
      discussed. EXPERT OPINION: The applicability of exon skipping as a therapy to DMD
      is restricted and the development of alternative strategies that are more
      encompassing is needed. The rapid pre-clinical advances that are being made in
      the field of adeno-associated virus (AAV)-based delivery of micro-dystrophin
      would address this. The obstacles to be faced with gene replacement strategies
      would include the need for high viral titres, efficient muscle targeting and
      avoidance of immune response to vector and transgene. The new emerging field of
      gene editing could potentially provide permanent correction of the DMD gene and
      the feasibility of such an approach to DMD is discussed.

PMID- 24308294
TI  - Surfactin triggers biofilm formation of Bacillus subtilis in melon phylloplane
      and contributes to the biocontrol activity.
AB  - The biocontrol activity of many Bacillus species has been traditionally related
      to the direct antagonism of pathogens. In previous works, we reported that B.
      subtilis strain UMAF6614 was an efficient biocontrol agent that produced
      bacillomycin, fengycin and surfactin lipopeptides. Bacillomycins and fengycins
      were shown to have antagonistic activity towards fungal and bacterial pathogens
      of cucurbits; however, the functionality of surfactin remained unclear. In this
      study, the role of surfactin in the biocontrol activity of this strain was
      investigated. We observed that a deficiency in surfactin production led to a
      partial reduction of disease suppression by this biocontrol agent, which
      coincided with a defect in biofilm formation and the colonization of the melon
      phylloplane. These effects were due to a dramatic reduction in the production of
      exopolysaccharide and the TasA protein, which are the two major components of the
      extracellular matrix. We propose that the biocontrol activity of this strain is
      the result of the coordinated action of the three families of lipopeptides. B.
      subtilis UMAF6614 produces surfactin to trigger biofilm formation on melon
      phylloplane, which ensures the long-term persistence and the adequate secretion
      of suppressive lipopeptides, bacillomycins and fengycins, which efficiently
      target pathogens. 

PMID- 24308295
TI  - Glomerular tip adhesions predict the progression of IgA nephropathy.
AB  - BACKGROUND: Focal segmental glomerulosclerosis-like lesions have been proposed to
      be predictive factors for IgA nephropathy. This single center, retrospective
      cohort study was designed to clarify which clinical and pathological factors are
      predictive of decreased estimated glomerular filtration rate (eGFR) at 5 and 10
      years in IgA nephropathy patients. METHODS: Of the 229 patients with IgA
      nephropathy who were admitted to Aichi Medical University Hospital between 1986
      and 2010, 57 were included in this study during the 5 to 10 years after renal
      biopsy. Clinical, laboratory, and pathological parameters were analyzed by
      multiple linear regression analysis with backward elimination to determine
      independent risk factors. After identifying such factors, we compared patients
      with and without each factor using the Student's t test, Wilcoxon test, or Mann
      Whitney U test. RESULTS: Four variables were identified as predictive factors for
      progression of IgA nephropathy: initial eGFR (p = 0.0002), glomerular tip
      adhesion (p = 0.004), global sclerosis (p = 0.019), and diastolic blood pressure
      (p = 0.024). The annual decrease in eGFR of patients with (n = 9) or without
      glomerular tip adhesions (n = 48) was 4.13 +/- 3.58 and 1.49 +/- 2.89 ml/min/1.73
      m2, respectively (p = 0.015). Serum total cholesterol levels were 231 +/- 45
      mg/dl and 196 +/- 42 mg/dl, respectively (two-sided p = 0.064; one-sided p =
      0.032). CONCLUSIONS: The presence of glomerular tip adhesions predicts the
      progression of IgA nephropathy. High levels of serum total cholesterol may affect
      glomerular tip adhesions.

PMID- 24308296
TI  - Relationship between the concentrations of dissolved organic matter and
      polycyclic aromatic hydrocarbons in a typical U.K. upland stream.
AB  - Concentrations of total and freely dissolved polycyclic aromatic hydrocarbons
      (PAHs) and dissolved organic carbon (DOC) were measured in water collected during
      four sampling events at five sites from the River Wyre. The sites are typical of
      streams draining upland organically rich soils in northwest U.K. Freely dissolved
      PAHs were separated from those associated with DOC using a flocculation method.
      The sum of concentrations of the total and freely dissolved PAHs analyzed ranged
      from 2.71 to 18.9 ng/L and 2.61 to 16.8 ng/L, respectively. PAH concentrations
      and PAH fluxes derived from concentrations and water flow rates generally
      increased downstream, the trend in the latter being more pronounced. The
      concentration of individual PAHs containing five or more aromatic rings was found
      to be strongly correlated to the DOC concentration (p < 0.0001), suggesting
      common terrestrial sources and hydrological pathways. In contrast, no significant
      relationships were observed between concentrations of PAHs with four or fewer
      rings and DOC. Concentrations of PAHs with more than four rings showed similar
      seasonal variation as DOC concentration (peaking in the late summer), while
      variation in two or three ring PAHs was out of phase with DOC (peaking in the
      winter). As the PAH-DOC relationship appeared partly dependent on the molecular
      weight of the PAHs, a linear regression function that included an interaction
      between this variable and DOC concentration was used to model PAH concentrations
      over a 2 year period to estimate annual fluxes. The relationship identified
      between PAH concentrations and DOC should help to enhance interpretation of PAH
      monitoring data that are currently sparse both spatially and temporally and,
      thus, enable more robust assessments of the potential risks of these
      environmental pollutants to sensitive aquatic organisms and human water supplies.

PMID- 24308297
TI  - Dose-related regulatory effect of intravenous immunoglobulin on dendritic cells
      mediated immune response.
AB  - CONTEXT: Intravenous immunoglobulin (IVIG) has been successfully applied in
      immune-related diseases of adults and neonates, such as human immunodeficiency
      virus (HIV) infection and systemic lupus erythematosus (SLE). OBJECTIVE: This
      study aims to investigate the distinct impacts of IVIG on cultured dendritic
      cells (DCs) from newborn and healthy adult. MATERIALS AND METHODS: Blood samples
      were collected from eight full-term newborns and eight healthy adult volunteers.
      DCs from cord blood and peripheral blood were both cultured in the RPMI 1640
      medium containing 10% fetal calf serum, 50 ng/ml granulocyte/macrophage colony
      stimulating factor (GM-CSF) and 10 ng/ml recombinant human interleukin-4 (rhIL-4)
      for 5 d with therapeutic IVIG (20 mg/ml) or physiological IVIG (10 mg/ml).
      Lipopolysaccharides (LPSs, 1 MUg/ml) were added on the fifth day to induce the
      maturation of immature DCs. The phagocytosis of monocytes, expression of MR
      (mannose receptor), CD14, CD1a, CD80, CD83, CD86 and MHC II were examined by flow
      cytometry. The expression of IL-4 mRNA was detected by RT-PCR, while IFN-gamma,
      IL-12 and IL-10 were analyzed by enzyme-linked immunosorbent assay (ELISA)
      commercial kits. RESULTS: IVIG of therapeutic dose inhibited the phagocytosis,
      differentiation and maturation of DCs, whereas physiological dose exhibited an
      accelerated role in vitro, especially on DCs from neonates, but aroused different
      effects on cytokine secretion. DISCUSSION AND CONCLUSION: The different responses
      are generally due to immature immune system of neonate, which has a limit
      capacity to maintain immunity homeostasis. Modulation of DCs phagocytosis,
      differentiation, maturation and cytokine secretion by IVIG is of potential
      relevance to its dosage and immune status of patients.

PMID- 24308298
TI  - Longitudinal gait development and variability of growing pigs reared on three
      different floor types.
AB  - Biomechanical investigation into locomotor pathology in commercial pigs is
      lacking despite this being a major concern for the industry. Different floor
      types are used in modern, intensive pig production systems at different stages of
      the pigs' production cycle. The general perception holds that slatted and/or hard
      solid concrete surfaces are inferior to soft straw-covered floors regarding
      healthy musculoskeletal development. Previous studies have compared pigs housed
      on different floor types using clinical, subjective assessment of leg weakness
      and lameness. However, reliability studies generally report a low repeatability
      of clinical lameness scoring. The objective of this study was to quantitatively
      assess the long-term effect of pen floors, reflected in the biomechanical gait
      characteristics and associated welfare of the pigs. A cohort of 24 pigs housed on
      one of three different floor types was followed from 37 to 90 kg average
      liveweight, with gait analysis (motion capture) starting at 63 kg. The three
      floor types were fully slatted concrete, partly slatted concrete and deep straw
      bedded surfaces, all located within the same building. Pigs underwent five
      repeated camera-based motion captures, 7 to 10 days apart, during which 3D
      coordinate data of reflective skin markers attached to leg anatomical landmarks
      were collected. Pigs walked on the same solid concrete walkway during captures.
      One-way ANOVA and repeated measures ANOVA were used to analyse the gait data.
      Results revealed changes over time in the spatiotemporal gait pattern which were
      similar in magnitude and direction for the pigs from different floor types.
      Significant increases in elbow joint flexion with age were observed in all pigs
      (P?0.050; +6 degrees ). There were few differences between floor groups, except
      for the step-to-stride ratio in the hind legs being more irregular in pigs housed
      on partly slatted floors (P=0.012; 3.6 times higher s.d.) compared with those on
      5 to 10 cm straw-bedding in all pen areas. As the level of clinical problems was
      generally low in this cohort, it may be that floors elicit problems only when
      there is a primary predisposing factor increasing weakness in susceptible
      tissues.

PMID- 24308299
TI  - A single center experience in 266 patients of infantile malignancies.
AB  - INTRODUCTION: The diagnosis and management of cancer in infantile age group is a
      significant challenge to pediatric oncologists. Malignancies occurring in infants
      often have different clinical and biological behavior in comparison to older
      children. This study was performed with an aim to find out the profile of
      infantile cancers at a tertiary care cancer center in South India. METHODS: The
      present study was a retrospective analysis of infants presenting with malignancy
      between 2003 and 2012 to our center in South India. RESULT: A total of 4588
      pediatric patients were registered in the Department of Pediatric Oncology at our
      institute between 2003 and 2012. Among those, 266 (5.79%) of the patients were
      infants (0-1 years). There were 65.75% males and 34.25% females. Solid tumors
      were the most common malignancy in this age group (72.56%). Leukemias were
      observed in 67 (25.19%) infants. ALL was the most common hematological malignancy
      (17.29%) followed by AML (5.64%). Common solid tumors in descending orders were
      neuroblastoma, soft tissue sarcoma, renal tumors, germ cell tumors,
      retinoblastoma and hepatoblastoma. Thirteen (4.89%) neonates were seen in our
      study. The most common malignancy in neonates was neuroblastoma. CONCLUSION: The
      distribution of malignancy in infants is quite different from that which is found
      in older children. Although neuroblastoma is the most common infantile tumor in
      western countries, in our study leukemia is the most common infantile malignancy.
      Embryonal tumors such as neuroblastoma, Wilms tumor, retinoblastoma, and
      hepatoblastoma were more prevalent in infants. Solid tumors were the most common
      malignancy in infants which is followed by leukemia.

PMID- 24308300
TI  - Submaximal exercise testing may be superior to the 6-min walk test in assessing
      pulmonary arterial hypertension disease severity.
AB  - INTRODUCTION: Submaximal exercise testing (SET) assesses functional exercise
      capacity in pulmonary arterial hypertension (PAH) patients and provides
      additional physiologic information compared with the 6-min walk test (6MWT). The
      relative correlations of the 6MWT and SET using SHAPE-HFTM with other markers of
      PAH severity, particularly echocardiogram (ECHO)-derived mean pulmonary artery
      pressure (MPAP), have not been investigated. OBJECTIVES: (i) Examine the
      correlation between SHAPE measures with the 6-min walk distance (6MWD), and (ii)
      Compare SHAPE parameters and the 6MWD to clinical measures of PAH severity.
      METHODS: Fifty-five consecutive group 1 PAH outpatients were evaluated in a
      single pulmonary hypertension referral center from March 2011 to June 2012. DATA
      COLLECTED: World Health Organization (WHO) functional class (FC), brain
      natriuretic peptide (BNP), ECHO, 6MWD and SHAPE results. Data are reported using
      mean +/- standard deviation and Spearman correlation coefficients (r). RESULTS:
      Nine patients were excluded. Of the 46 remaining patients, 78% were women and the
      average age was 61 +/- 13 years. PAH characteristics: WHO FC III-IV 48%;
      idiopathic PAH 52%; BNP 198 +/- 277 pg/mL; 6MWD 399 +/- 97 m; ECHO right atrial
      pressure (RAP) 7 +/- 4, pulmonary artery systolic pressure (PASP) 63 +/- 29 and
      MPAP 45 +/- 17 mmHg. SET with SHAPE results: mean partial pressure of end-tidal
      (PET ) CO2 31 +/- 6 mmHg at end-exercise; ventilatory efficiency (VE/VCO2 ) 43 +/
      16. Significant correlations were found between the 6MWD and SHAPE variables:
      VE/VCO2 (r = -0.57, P < 0.0001) and end-exercise PET CO2 (r = 0.42, P = 0.004).
      VE/VCO2 correlated with WHO FC, BNP, RAP, MPAP and PASP and 6MWD only with WHO
      FC, BNP and PASP. CONCLUSION: SHAPE outperformed 6MWD in comparison with other
      measures of PAH disease severity.

PMID- 24308301
TI  - Trial-based clinical and economic analyses: the unhelpful quest for conformity.
AB  - Where there is conformity across the findings, interpretation and implications of
      'clinical' and 'economic' research, there is limited cause for concern. However,
      there is often unease when apparent contradictory conclusions are drawn from the
      same study. Given the ever increasing role for economic evaluation in healthcare
      decision making, this commentary challenges the necessity of compatibility
      between clinical and economic evaluation. 

PMID- 24308302
TI  - Processing genome scale tabular data with wormtable.
AB  - BACKGROUND: Modern biological science generates a vast amount of data, the
      analysis of which presents a major challenge to researchers. Data are commonly
      represented in tables stored as plain text files and require line-by-line parsing
      for analysis, which is time consuming and error prone. Furthermore, there is no
      simple means of indexing these files so that rows containing particular values
      can be quickly found. RESULTS: We introduce a new data format and software
      library called wormtable, which provides efficient access to tabular data in
      Python. Wormtable stores data in a compact binary format, provides random access
      to rows, and enables sophisticated indexing on columns within these tables. Files
      written in existing formats can be easily converted to wormtable format, and we
      provide conversion utilities for the VCF and GTF formats. CONCLUSIONS:
      Wormtable's simple API allows users to process large tables orders of magnitude
      more quickly than is possible when parsing text. Furthermore, the indexing
      facilities provide efficient access to subsets of the data along with providing
      useful methods of summarising columns. Since third-party libraries or custom code
      are no longer needed to parse complex plain text formats, analysis code can also
      be substantially simpler as well as being uniform across different data formats.
      These benefits of reduced code complexity and greatly increased performance allow
      users much greater freedom to explore their data.

PMID- 24308303
TI  - Molecular markers reveal narrow genetic base and culturing-associated genetic
      drift in Teretrius nigrescens Lewis populations released for the biological
      control of the larger grain borer in Africa.
AB  - In biological control, successful establishment of a natural enemy species
      depends on its adaptability in the introduced range including its ability to re
      establish desired ecological interactions with the pest. These are affected by
      genetic parameters hitherto largely unresolved in biological control. The larger
      grain borer (LGB), Prostephanus truncatus, an invasive species from meso-America,
      is the most important post-harvest pest of maize in Africa. We studied the
      genetic structure of Teretrius nigrescens, a predatory beetle previously released
      for the control of the pest in Africa, to test the hypothesis that establishment
      patterns were a result of ecotype-environment mismatch and to follow up on our
      earlier reports of distinct lineages of the predator. We studied 13 populations
      of T. nigrescens, using 16 polymorphic microsatellite markers. Five genetic
      populations with a hierarchical structure and significant isolation by distance
      were detected. The most diverse population was found in southern Mexico,
      consistent with earlier lineage coexistence observations. Populations introduced
      to Africa maintained genetic similarity to local geographic populations of their
      area of origin. The more successful Benin releases were also more genetically
      diverse. Loss of rare alleles and a higher frequency of existing private alleles
      in some populations indicated population expansions following bottleneck events.
      Sustainable biological control should accommodate pest and natural enemy species,
      and monitor genetic changes associated with introduction and release. 

PMID- 24308304
TI  - Hospital accreditation, reimbursement and case mix: links and insights for
      contractual systems.
AB  - BACKGROUND: Resource consumption is a widely used proxy for severity of illness,
      and is often measured through a case-mix index (CMI) based on Diagnosis Related
      Groups (DRGs), which is commonly linked to payment. For countries that do not
      have DRGs it has been suggested to use CMIs derived from International
      Classification of Diseases (ICD). Our research objective was to use ICD-derived
      case-mix to evaluate whether or not the current accreditation-based hospital
      reimbursement system in Lebanon is appropriate. METHODS: Our study population
      included medical admissions to 122 hospitals contracted with the Lebanese
      Ministry of Public Health (MoPH) between June 2011 and May 2012. Applying ICD
      derived CMI on principal diagnosis cost (CMI-ICDC) using weighing similar to that
      used in Medicare DRG CMI, analyses were made by hospital accreditation, ownership
      and size. We examined two measures of 30-day re-admission rate. Further analysis
      was done to examine correlation between principal diagnosis CMI and surgical
      procedure cost CMI (CMI-CPTC), and three proxy measures on surgical complexity,
      case complexity and surgical proportion. RESULTS: Hospitals belonging to the
      highest accreditation category had a higher CMI than others, but no difference
      was found in CMI among the three other categories. Private hospitals had a higher
      CMI than public hospitals, and those more than 100 beds had a higher CMI than
      smaller hospitals. Re-admissions rates were higher in accreditation category C
      hospitals than category D hospitals. CMI-ICDC was fairly correlated with CMI
      CPTC, and somehow correlated with the proposed proxies. CONCLUSIONS: Our results
      indicate that the current link between accreditation and reimbursement rate is
      not appropriate, and leads to unfairness and inefficiency in the system. Some
      proxy measures are correlated with case-mix but are not good substitutes for it.
      Policy implications of our findings propose the necessity for changing the
      current reimbursement system by including case mix and outcome indicators in
      addition to accreditation in hospital contracting. Proxies developed may be used
      to detect miss-use and provider adverse behavior. Research using ICD-derived case
      mix is limited and our findings may be useful to inform similar initiatives and
      other limited-setting countries in the region.

PMID- 24308305
TI  - Incidence of first ever stroke during Hajj ceremony.
AB  - BACKGROUND: The Hajj Ceremony, the largest annual gathering in the world, is the
      most important life event for any Muslim. This study was designed to evaluate the
      incidence of stroke among Iranian pilgrims during the Hajj ceremony. METHODS: We
      ascertained all cases of stroke occurring in a population of 92,974 Iranian
      pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk
      factors of the first ever stroke in Hajj pilgrims were compared, within the same
      time frame, to those of the Mashhad residents, the second largest city in Iran.
      Data for the latter group were extracted from the Mashhad Stroke Incidence Study
      (MSIS) database. RESULTS: During the study period, 17 first-ever strokes occurred
      in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group.
      Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was
      lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and
      gender-specific subgroups, the Hajj stroke crude rates were in general similar to
      or lower than the general population of Mashhad, Iran, with the exception of
      women aged 35 to 44 years and aged >75 years who were at greater risk of having
      first-ever stroke than the non-pilgrims of the same age. CONCLUSION: The first
      ever stroke rate among Iranian Hajj pilgrims was lower than that of the general
      population in Mashhad, Iran, except for females 35-44 or more than 75 years old.
      The number of events occurring during the Hajj suggests that Islamic countries
      should consider designing preventive and screening programs for pilgrims.

PMID- 24308306
TI  - W. W. "Mo" Cleland: a catalytic life.
AB  - Professor W. Wallace Cleland, the architect of modern steady-state enzyme
      kinetics, died on March 6, 2013, from injuries sustained in a fall outside of his
      home. He will be most remembered for giving the enzyme community Ping-Pong
      kinetics and the invention of dithiothreitol (DTT). He pioneered the utilization
      of heavy atom isotope effects for the elucidation of the chemical mechanisms of
      enzyme-catalyzed reactions. His favorite research journal was Biochemistry, in
      which he published more than 135 papers beginning in 1964 with the disclosure of
      DTT. 

PMID- 24308308
TI  - Nanocasting synthesis of In2O3 with appropriate mesostructured ordering and
      enhanced gas-sensing property.
AB  - Ordered mesoporous In2O3 gas-sensing materials with controlled mesostructured
      morphology and high thermal stability have been successfully synthesized via a
      nanocasting method in conjunction with the container effect. The mesostructured
      ordering, as well as the particle size, crystallinity and pore size distribution
      have been proved to vary in a large range by using the XRD, SAXRD, SEM, TEM, and
      nitrogen physisorption techniques. The control of the mesostructured morphology
      was carried out by tuning the transportation rate of indium precursor in template
      channel resulting from the different escape rate of the decomposed byproducts via
      the varied container opening and shapes. The particular relation between the
      mesostructured ordering and gas sensing property of mesoporous In2O3 was examined
      in detail. It was found that the ordered mesoporous In2O3 with appropriate
      mesostructured morphology exhibited significantly improved ethanol sensitivity,
      response and selectivity performances in comparison with the other ordered
      mesoporous In2O3, which benefits from the large surface area with enough sensing
      active sites, proper pore distribution for sufficient gas diffusion, and
      appropriate particle size for effective electron depletion. The resulting sensing
      behaviors lead to a better understanding of designing and using such mesoporous
      metal oxides for a number of gas-sensing applications. 

PMID- 24308307
TI  - Primary porcine proximal tubular cells as an alternative to human primary renal
      cells in vitro: an initial characterization.
AB  - BACKGROUND: A good in vitro model should approximate an in vivo-like behavior as
      closely as possible in order to reflect most likely the in vivo situation.
      Regarding renal physiology of different species, humans are more closely related
      to pigs than to rodents, therefore primary porcine kidney cells (PKC) and their
      subsequent cell strain could be a valid alternative to primary human cells for
      renal in vitro toxicology. For this PKC must display inherent characteristics
      (e.g. structural organization) and functions (e.g. transepithelial transport) as
      observed under in vivo conditions within the respective part of the kidney.
      RESULTS: We carried out a comprehensive characterization of PKC and their
      subsequent cell strain, including morphology and growth as well as transporter
      expression and functionality. The data presented here demonstrate that PKC
      express various transporters including pMrp1 (abcc1), pMrp2 (abcc2), pOat1
      (slc22a6) and pOat3 (slc22a8), whereas pMdr1 (abcb1) and pOatp1a2 (slco1a2) mRNA
      could not be detected in either the PKCs or in the porcine cortical tissue.
      Functionality of the transporters was demonstrated by determining the specific
      PAH transport kinetics. CONCLUSIONS: On the basis of the presented results it can
      be concluded that PKC and to some extent their subsequent cell strain represent a
      valuable model for in vitro toxicology, which might be used as an alternative to
      human primary cells.

PMID- 24308309
TI  - Effect of cultivation practices on the beta-glucan content of Agaricus
      subrufescens basidiocarps.
AB  - The present work aimed to assess the effect of the following treatments on the
      medicinal potential (beta-glucan content) and agronomical performance (yield) of
      Agaricus subrufescens: five different fungal strains, three cultivation
      substrates (compost), four casing layers, and four cultivation environments. Two
      experiments were performed, and the results indicate that the greatest
      contribution to the variation in beta-glucan content was the strain (35.8%),
      followed by the casing layer (34.5%), the cultivation environment (15.7%), and
      the type of compost (9.9%). On the other hand the variation in yield was affected
      most by the cultivation environment (82.1%), followed by the strain (81.3%),
      casing layer (49.1%), and compost type (15.2%). These findings underscore the
      importance of developing a production protocol that employs specific cultivation
      practices for improving mushroom yield as well as beta-glucan content.

PMID- 24308311
TI  - Double role of the hydroxy group of phosphoryl in palladium(II)-catalyzed ortho
      olefination: a combined experimental and theoretical investigation.
AB  - Density functional theory calculations have been carried out on Pd-catalyzed
      phosphoryl-directed ortho-olefination to probe the origin of the significant
      reactivity difference between methyl hydrogen benzylphosphonates and dimethyl
      benzylphosphonates. The overall catalytic cycle is found to include four basic
      steps: C-H bond activation, transmetalation, reductive elimination, and recycling
      of catalyst, each of which is constituted from different steps. Our calculations
      reveal that the hydroxy group of phosphoryl plays a crucial role almost in all
      steps, which can not only stabilize the intermediates and transition states by
      intramolecular hydrogen bonds but also act as a proton donor so that the eta(1)
      CH3COO(-) ligand could be protonated to form a neutral acetic acid for easy
      removal. These findings explain why only the methyl hydrogen benzylphosphonates
      and methyl hydrogen phenylphosphates were found to be suitable reaction partners.
      Our mechanistic findings are further supported by theoretical prediction of Pd
      catalyzed ortho-olefination using methyl hydrogen phenylphosphonate, which is
      verified by experimental observations that the desired product was formed in a
      moderate yield. 

PMID- 24308310
TI  - The effect of Baduanjin exercise for physical and psychological wellbeing of
      college students: study protocol for a randomized controlled trial.
AB  - BACKGROUND: The physical and mental health of college students tends to
      continuously decline around the world. Since they are in a significant transition
      period which presents opportunities and challenges in health promotion, it is
      important to improve their health in this period. As a traditional Chinese
      exercise form which combines movements with breath and mind, Baduanjin may be one
      of the selectable effective exercises. However, evidence of Baduanjin exercise
      for college students has not been completely established. The primary aim of this
      trial is to evaluate the effectiveness and safety of Baduanjin exercise for
      physical and mental health of college students through a rigorous randomization,
      parallel-controlled design. METHOD/DESIGN: We will conduct a randomized, single
      blind, parallel-controlled trial. A total of 222 college students from Fujian
      University of Traditional Chinese Medicine who meet the eligibility criteria will
      be recruited and randomly allocated into Baduanjin training or usual exercise
      control group. Baduanjin training will last 12 weeks (1 h per day, 5 days per
      week). The physical and psychological outcomes, including lumbar muscle strength,
      lumbar proprioception function, physical fitness, as well as self-reported
      symptom intensity, stress, self-esteem, mood, quality of life, quality of sleep,
      and adverse events, will be evaluated by blinded outcome assessors at baseline,
      13 weeks (at the end of intervention), and 25 weeks (after the 12-week follow-up
      period). DISCUSSION: This protocol presents an objective design of a randomized,
      single-blind trial that aims to evaluate the effectiveness and safety of
      Baduanjin exercise for physical and mental health of college students. If the
      outcome is positive, the results will provide higher-quality evidence to better
      inform the college students regarding their selection about whether to receive
      such exercise. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC
      13003329. Registration date: 18 July, 2013.

PMID- 24308312
TI  - Managers' reactions towards employees' disclosure of psychiatric or somatic
      diagnoses.
AB  - AIMS: To study whether employees who disclose a psychiatric diagnosis, such as
      depression risk stigmatisation and discrimination at the workplace. METHODS:
      Randomised experimental study with 748 managers from German companies
      incorporating four case vignettes displaying an employee with different
      'diagnoses' (depression, burnout, private crisis and thyroid dysfunction), but
      identical unspecific complaints. Main outcome measures were the managers'
      attitudes and their impact on stigmatisation with respect to job performance.
      RESULTS: In nearly all aspects of job performance, the diagnosis depression
      (psychiatric disorder) was seen as more critical than the diagnosis of a thyroid
      dysfunction (somatic disease). The diagnosis 'burnout' did not prove to be less
      stigmatising than 'depression'. Likewise 'private crisis' was rated less
      favourably than thyroid dysfunction. CONCLUSIONS: Therefore, employees have to
      evaluate if they disclose their psychiatric disorder or if they conceal it as a
      somatic illness.

PMID- 24308313
TI  - DABSO-based, three-component, one-pot sulfone synthesis.
AB  - The addition of Grignard reagents or organolithium reagents to the SO2-surrogate
      DABSO generates a diverse set of metal sulfinates, suitable for direct conversion
      to sulfone products. The metal sulfinates can be trapped in situ with a wide
      range of C-electrophiles, including alkyl, allyl, and benzyl halides, epoxides,
      and (hetero)aryliodoniums. 

PMID- 24308315
TI  - Sequential electrochemical unzipping of single-walled carbon nanotubes to
      graphene ribbons revealed by in situ Raman spectroscopy and imaging.
AB  - We report an in situ Raman spectroscopic and microscopic investigation of the
      electrochemical unzipping of single-walled carbon nanotubes (SWNTs). Observations
      of the radial breathing modes (RBMs) using Raman spectral mapping reveal that
      metallic SWNTs are opened up rapidly followed by gradual unzipping of
      semiconducting SWNTs. Consideration of the resonant Raman scattering theory
      suggests that two metallic SWNTs with chiralities (10, 4) and (12, 0) get
      unzipped first at a lower electrode potential (0.36 V) followed by the gradual
      unzipping of another two metallic tubes, (9, 3) and (10, 1), at a relatively
      higher potential (1.16 V). The semiconducting SWNTs with chiralities (11, 7) and
      (12, 5), however, get open up gradually at +/-1.66 V. A rapid decrease followed
      by a subsequent gradual decrease in the metallicity of the SWNT ensemble as
      revealed from a remarkable variation of the peak width of the G band complies
      well with the variations of RBM. Cyclic voltammetry also gives direct evidence
      for unzipping in terms of improved capacitance after oxidation followed by more
      important removal of oxygen functionalities during the reduction step, as
      reflected in subtle changes of the morphology confirming the formation of
      graphene nanoribbons. The density functional-based tight binding calculations
      show additional dependence of chirality and diameter of nanotubes on the epoxide
      binding energies, which is in agreement with the Raman spectroscopic results and
      suggests a possible mechanism of unzipping determined by combined effects of the
      structural characteristics of SWNTs and applied field. 

PMID- 24308314
TI  - Measuring telomere length for the early detection of precursor lesions of
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Esophageal cancer is the sixth leading cause of cancer death
      worldwide; current early detection screening tests are inadequate. Esophageal
      balloon cytology successfully retrieves exfoliated and scraped superficial
      esophageal epithelial cells, but cytologic reading of these cells has poor
      sensitivity and specificity for detecting esophageal squamous dysplasia (ESD),
      the precursor lesion of esophageal squamous cell carcinoma (ESCC). Measuring
      telomere length, a marker for chromosomal instability, may improve the utility of
      balloon cytology for detecting ESD and early ESCC. METHODS: We examined balloon
      cytology specimens from 89 asymptomatic cases of ESD (37 low-grade and 52 high
      grade) and 92 age- and sex-matched normal controls from an esophageal cancer
      early detection screening study. All subjects also underwent endoscopy and
      biopsy, and ESD was diagnosed histopathologically. DNA was extracted from the
      balloon cytology cells, and telomere length was measured by quantitative PCR. A
      receiver operating characteristic (ROC) curve was plotted for telomere length as
      a diagnostic marker for high-grade dysplasia. RESULTS: Telomere lengths were
      comparable among the low- and high-grade dysplasia cases and controls, with means
      of 0.96, 0.96, and 0.92, respectively. The area under the ROC curve was 0.55 for
      telomere length as a diagnostic marker for high-grade dysplasia. Further
      adjustment for subject characteristics, including sex, age, smoking, drinking,
      hypertension, and body mass index did not improve the use of telomere length as a
      marker for ESD. CONCLUSIONS: Telomere length of esophageal balloon cytology cells
      was not associated with ESCC precursor lesions. Therefore, telomere length shows
      little promise as an early detection marker for ESCC in esophageal balloon
      samples.

PMID- 24308316
TI  - Before and beyond the micellization of n-alkyl glycosides. A water-1H NMR
      relaxation study.
AB  - The interactions between the headgroups of n-alkyl glycoside (AG) and water
      molecules were studied by nuclear magnetic transverse relaxation times (T2) of
      the water protons before and beyond the micellization. Despite the low
      concentration of the surfactants (mM), their micellization induce strong effect
      on the T2 values of bulk water when the AG molecules self-aggregate into
      micelles. This is associated with the decreasing of the fraction of OH headgroups
      of AG to exchange protons with water molecules due to the OH headgroups
      intermolecular interactions of AG at the micelle surface. These findings support
      the computational results described in the literature, which indicate that the
      water hydrogen bonding to OH headgroups is perturbed at AG micelle surfaces. 

PMID- 24308317
TI  - Household catastrophic medical expenses in eastern China: determinants and policy
      implications.
AB  - BACKGROUND: Much of research on household catastrophic medical expenses in China
      has focused on less developed areas and little is known about this problem in
      more developed areas. This study aimed to analyse the incidence and determinants
      of catastrophic medical expenses in eastern China. METHODS: Data were obtained
      from a health care utilization and expense survey of 11,577 households conducted
      in eastern China in 2008. The incidence of household catastrophic medical
      expenses was calculated using the method introduced by the World Health
      Organization. A multi-level logistic regression model was used to identify the
      determinants. RESULTS: The incidence of household catastrophic medical expenses
      in eastern China ranged from 9.24% to 24.79%. Incidence of household catastrophic
      medical expenses was lower if the head of household had a higher level of
      education, labor insurance coverage, while the incidence was higher if they lived
      in rural areas, had a family member with chronic diseases, had a child younger
      than 5 years old, had a person at home who was at least 65 years old, and had a
      household member who was hospitalized. Moreover, the impact of the economic level
      on catastrophic medical expenses was non-linear. The poorest group had a lower
      incidence than that of the second lowest income group and the group with the
      highest income had a higher incidence than that of the second highest income
      group. In addition, region was a significant determinant. CONCLUSIONS: Reducing
      the incidence of household catastrophic medical expenses should be one of the
      priorities of health policy. It can be achieved by improving residents' health
      status to reduce avoidable health services such as hospitalization. It is also
      important to design more targeted health insurance in order to increase financial
      support for such vulnerable groups as the poor, chronically ill, children, and
      senior populations.

PMID- 24308318
TI  - Fate of polyfluoroalkyl phosphate diesters and their metabolites in biosolids
      applied soil: biodegradation and plant uptake in greenhouse and field
      experiments.
AB  - Significant contamination of perfluoroalkyl acids (PFAAs) in wastewater treatment
      plant (WWTP) sludge implicates the practice of applying treated sludge or
      biosolids as a potential source of these chemicals onto agricultural farmlands.
      Recent efforts to characterize the sources of PFAAs in the environment have
      unveiled a number of fluorotelomer-based materials that are capable of degrading
      to the perfluoroalkyl carboxylates (PFCAs), such as the polyfluoroalkyl phosphate
      diesters (diPAPs), which have been detected in WWTP and paper fiber biosolids.
      Here, a greenhouse microcosm was used to investigate the fate of endogenous
      diPAPs and PFCAs present in WWTP and paper fiber biosolids upon amendment of
      these materials with soil that had been sown with Medicago truncatula plants.
      Biodegradation pathways and plant uptake were further elucidated in a separate
      greenhouse microcosm supplemented with high concentrations of 6:2 diPAP. Biosolid
      amended soil exhibited increased concentrations of diPAPs (4-83 ng/g dry weight
      (dw)) and PFCAs (0.1-19 ng/g dw), as compared to control soils (nd-1.4 ng/g dw).
      Both plant uptake and biotransformation contributed to the observed decline in
      diPAP soil concentrations over time. Biotransformation was further evidenced by
      the degradation of 6:2 diPAP to its corresponding fluorotelomer intermediates and
      C4-C7 PFCAs. Substantial plant accumulation of endogenous PFCAs present in the
      biosolids (0.1-138 ng/g wet weight (ww)) and those produced from 6:2 diPAP
      degradation (100-58 000 ng/g ww) were observed within 1.5 months of application,
      with the congener profile dominated by the short-chain PFCAs (C4-C6). This
      pattern was corroborated by the inverse relationship observed between the plant
      soil accumulation factor (PSAF, Cplant/Csoil) and carbon chain length (p < 0.05,
      r = 0.90-0.97). These results were complemented by a field study in which the
      fate of diPAPs and PFCAs was investigated upon application of compost and paper
      fiber biosolids to two farm fields. Together, these studies provide the first
      evidence of soil biodegradation of diPAPs and the subsequent uptake of these
      chemicals and their metabolites into plants. 

PMID- 24308319
TI  - Perceived discrimination and ethnic affirmation: Anglo culture orientation as a
      moderator among mexican-origin adolescent mothers.
AB  - This study examined whether Anglo culture orientation modified the association
      between adolescents' perceived ethnic discrimination and ethnic identity
      affirmation over time in a sample of Mexican-origin adolescent mothers (N = 205,
      Mage  = 16.24 years). Results indicated that perceived ethnic discrimination was
      significantly associated with decreases in ethnic identity affirmation over time
      for adolescents reporting high Anglo culture orientation, but no relation existed
      for adolescents reporting low Anglo culture orientation. Findings suggest that a
      person-environment mismatch (i.e., between adolescents' perceptions of their
      connection to Anglo culture and the messages they receive from others regarding
      that connection in terms of perceived ethnic discrimination) may be detrimental
      to adolescents' development of positive feelings about their ethnicity. 

PMID- 24308320
TI  - Milking behaviour of buffalo cows: entrance order and side preference in the
      milking parlour.
AB  - On two farms, three milking groups of buffalo cows were used to assess the
      consistency of entrance order and the preference for one side of the milking
      parlour. On Farm 1 (F1) all animals were primiparous (n=57). On Farm 2, three
      primiparous, 16 secondiparous and 36 multiparous cows (range 1-8) constituted
      group F2G1; whereas group F2G2 had 12 primiparous, 10 secondiparous and 14
      multiparous cows (range 1-10). Animals were milked in auto-tandem milking
      parlours (2*5 and 2*6 for Farms 1 and 2, respectively). For each cow, entrance
      order into milking parlour, side where she was milked, milk yield, time and
      duration of milking were recorded. These data were derived from the computerised
      identification of cows. The sequence in which the cows entered the milking
      parlour ranged from 1 to 57 for group F1, from 1 to 55 for group F2G1 and from 1
      to 36 for group F2G2. The analysis of data was conducted on 130, 120 and 92
      consecutive milkings for groups F1, F2G1 and F2G2, respectively. Kendall's
      coefficients of concordance showed a strong constancy of the entrance order into
      milking parlour for groups F1 (W=0.658; chi2=4792.81; P<0.001), F2G1 (W=0.779;
      chi2=5046.81; P<0.001) and F2G2 (W=0.624; chi2=2030.48; P<0.001). Spearman rank
      correlation coefficients indicated that the more productive cows in groups F1 and
      F2G1 tended to enter the milking parlour first (r s=-0.221 and r s=-0.215;
      P<0.10; respectively). In group F2G1, a negative correlation was found between
      duration of milking and order of entry in the milking parlour (r s=-0.265;
      P<0.05). Animals in group F2G2 (r s=0.334; P<0.05) with higher days in milk
      entered the milking parlour latterly. In all three groups, 68 cows (45.9%)
      preferred the right side of the milking parlour, 73 the left side (49.3%) and the
      remaining seven (4.8%) showed no preference. Finally, negative correlations were
      found between mean entrance order and parity for both groups of Farm 2 (r s=
      0.319; P<0.05 and r s=-0.325; P<0.05 for F2G1 and F2G2, respectively). As
      buffaloes showed higher entrance order consistency and side preference than other
      domestic ruminants, it is concluded that management practices that disturb their
      choice should be avoided in order to minimise stress during farming routines. 

PMID- 24308321
TI  - Probing the contribution of different intermolecular forces to the adsorption of
      spheroproteins onto hydrophilic surfaces.
AB  - Protein adsorption is a delicate process, which results from the balance between
      the properties of proteins and their solid supports. Although the relevance of
      some of these parameters has been already unveiled, the precise involvement of
      electrostatics and other weaker intermolecular forces requires further
      comprehension. Aiming to contribute to this task, this work explores the
      attachment, rearrangement, and surface aggregation of a model spheroprotein, such
      as bovine beta-lactoglobulin (beta-LG), onto hydrophilic substrates
      prefunctionalized with different alkylthiol films. Thereby, a variety of
      electrostatic scenarios for the adsorption of beta-LG could be recreated through
      the variation of the pH and the functional chemistry of the surfaces. The changes
      in surface mass density (plus associated water) and film flexibility were
      followed in situ with quartz crystal microbalance with dissipation monitoring.
      Film packing and aggregation were assessed by faradaic electrochemical
      measurements and ex situ atomic force microscopy and field effect scanning
      electron microscopy. In contrast to previous hypotheses arguing that
      electrostatic interactions between charged substrates and proteins would be the
      only driving force, a complex interplay between Coulombic and non-Coulombic
      intermolecular forces (which would depend upon the experimental conditions) has
      been suggested to explain the results. 

PMID- 24308322
TI  - An online, mindfulness-based, cognitive-behavioral therapy for female sexual
      difficulties: impact on relationship functioning.
AB  - This article presents the evaluation of an online treatment for female sexual
      difficulties as it relates to relationship functioning. Pursuing Pleasure was an
      online, mindfulness-based, cognitive behavioral therapy for female sexual
      difficulties. In Study 1, 26 women completed treatment and changes were compared
      with a waitlist control group (n = 31). In Study 2, 16 women from the control
      group then completed treatment. The authors did not use a control group in Study
      2. Results demonstrated that both treatment groups observed significant
      improvements in sexual intimacy and communication, and emotional intimacy
      improved significantly in the Study 1 treatment group. Most improvements were
      maintained at follow-up. 

PMID- 24308323
TI  - Osteogenically differentiated mesenchymal stem cells and ceramics for bone tissue
      engineering.
AB  - INTRODUCTION: In the human body, cells having self-renewal and multi
      differentiation capabilities reside in many tissues and are called adult stem
      cells. In bone marrow tissue, two types of stem cells are well known:
      hematopoietic stem cells and mesenchymal stem cells (MSCs). Though the number of
      MSCs in bone marrow tissue is very low, it can be increased by in vitro culture
      of the marrow, and culture-expanded MSCs are available for various tissue
      regeneration. AREAS COVERED: The culture-expanded MSCs can further differentiate
      into osteogenic cells such as bone forming osteoblasts by culturing the MSCs in
      an osteogenic medium. This paper discusses osteogenically differentiated MSCs
      derived from the bone marrow of patients. Importantly, the differentiation can be
      achieved on ceramic surfaces which demonstrate mineralized bone matrix formation
      as well as appearance of osteogenic cells. The cell/matrix/ceramic constructs
      could show immediate in vivo bone formation and are available for bone
      reconstruction surgery. EXPERT OPINION: Currently, MSCs are clinically available
      for the regeneration of various tissues due to their high
      proliferation/differentiation capabilities. However, the capabilities are still
      limited and thus technologies to improve or recover the inherent capabilities of
      MSCs are needed.

PMID- 24308324
TI  - Clinical features of three avian influenza H7N9 virus-infected patients in
      Shanghai.
AB  - INTRODUCTION: Since February 2013, a novel reassortant H7N9 virus associated with
      human deaths, but no apparent outbreaks in poultry and wild birds has emerged in
      eastern China. OBJECTIVES: The potential reemergence of H7N9 during next year's
      influenza season demand a further understanding of this important disease.
      METHODS: Between March 1 and April 30, 2013, we obtained and analyzed clinical,
      epidemiologic and radiologic features, and virologic data from three laboratory
      confirmed patients of A H7N9 infection admitted in Shanghai Ruijin Hospital.
      RESULTS: All patients were middle to old aged (mean age 62 years) and overweight
      (mean body mass index 31) patients. Two patients were exposed to poultry directly
      or indirectly in food market. They presented with fever and rapidly progressive
      pneumonia that did not respond to antibiotics. Time between onset of symptoms and
      onset of respiratory failure (days) were 7-11 days. Two patients presented
      secondary invasive bacterial infections. All patients died on day 7 to day 86
      after the onset of symptoms. CONCLUSIONS: Cross species poultry-to-person
      transmission of this new reassortant avian influenza H7N9 virus can result in
      severe and fatal respiratory disease like acute respiratory distress syndrome
      (ARDS) in humans. Reduplicate chest imaging examination is suggested for risky
      patients with fever and dyspnea. Secondary invasive bacterial infections and
      pneumothorax can cause severe and fatal consequence. Old age, obesity and
      presence of comorbidity may be associated with increased mortality. Pulmonary
      fibrosis can be seen at late stage of the disease.

PMID- 24308326
TI  - The moral experience of the patient with chronic pain: bridging the gap between
      first and third person ethics.
AB  - BACKGROUND: There has been a widespread call for an ethics in the management of
      patients with chronic pain which is patient centered and takes into account the
      lived experience of the patient. It has been argued in literature that current
      "duty" or principlist-based models of ethics (so-called 3rd person ethics) have
      not adequately addressed the needs of either patients or practitioners in this
      area. METHOD: Two strands of literature within phenomenology were reviewed: the
      literature of interpretative phenomenological analysis and the study of the lived
      experience of the person with chronic pain; and the contribution of phenomenology
      in neo-Aristotelian virtue ethics (1st person ethics). FINDINGS: Patients
      experience chronic pain in existential and moral terms in addition to their
      biomedical issues, facing dilemmas in understanding their own self-identity and
      in attempting to recover a sense of moral worth and agency. DISCUSSION: We
      outline a patient-centered ethics to underpin contemporary collaborative,
      multimodal approaches in the management of chronic pain. We firstly describe an
      agency-oriented, neo-Aristotelian 1st person ethics and then outline a
      hermeneutic relationship with extant "duty-based," 3rd person bioethics. The
      utility of the ethics model we propose (the ethical reasoning bridge) lies in its
      capacity for developing a sense of moral agency for both practitioner and
      patient, resonating with the current emphasis of seeking active engagement of
      patients in management.

PMID- 24308327
TI  - 6S RNA: recent answers--future questions.
AB  - 6S RNA is a non-coding RNA, found in almost all phylogenetic branches of
      bacteria. Through its conserved secondary structure, resembling open DNA
      promoters, it binds to RNA polymerase and interferes with transcription at many
      promoters. That way, it functions as transcriptional regulator facilitating
      adaptation to stationary phase conditions. Strikingly, 6S RNA acts as template
      for the synthesis of small RNAs (pRNA), which trigger the disintegration of the
      inhibitory RNA polymerase-6S RNA complex releasing 6S RNA-dependent repression.
      The regulatory implications of 6S RNAs vary among different bacterial species
      depending on the lifestyle and specific growth conditions that they have to face.
      The influence of 6S RNA can be seen on many different processes including
      stationary growth, sporulation, light adaptation or intracellular growth of
      pathogenic bacteria. Recent structural and functional studies have yielded
      details of the interaction between E. coli 6S RNA and RNA polymerase. Genome-wide
      transcriptome analyses provided insight into the functional diversity of 6S RNAs.
      Moreover, the mechanism and physiological consequences of pRNA synthesis have
      been explored in several systems. A major function of 6S RNA as a guardian
      regulating the economic use of cellular resources under limiting conditions and
      stress emerges as a common perception from numerous recent studies.

PMID- 24308328
TI  - The effects of resveratrol on flap survival in diabetic rats.
AB  - Resveratrol is an antioxidant agent with multiple positive impacts on the body.
      It is known to have anti-diabetic, anti-inflammatory, anti-carcinogenic, and
      neuroprotective effects. The goal of this study is to demonstrate the antioxidant
      and anti-diabetic effects of resveratrol on flap survival in diabetic rats.
      Streptozotocin-induced diabetic Sprague-Dawley albino rats were treated with 10
      mg/kg resveratrol following a flap surgery. Histological findings regarding
      polymorphonuclear leukocyte (PMNL) density, vascular proliferation, fibroblast
      density, and tissue necrosis were compared between resveratrol-treated and
      control rats. Significantly higher PMNL density was found in the control group (p
      = 0.005); while vascular proliferation and the fibroblast density were higher in
      the resveratrol group (p = 0.004 and p = 0.021, respectively). Collagen density
      was also higher in the resveratrol group and the difference has statistical
      significance (p = 0.024). Lymphocyte density was not significantly different
      between groups (p = 0.061). When the necrosis in the distal areas was evaluated
      histologically, 20% of the resveratrol group had epidermal tissue necrosis, thus
      90% of the control group had epidermal or full-layer necrosis. Resveratrol
      improved flap survival significantly in diabetic rats. Therefore, diabetic
      patients requiring complex reconstructive procedures may benefit from
      resveratrol; so, clinical trials are required to support this study.

PMID- 24308329
TI  - NrsZ: a novel, processed, nitrogen-dependent, small  non-coding RNA that
      regulates Pseudomonas  aeruginosa PAO1 virulence.
AB  - The opportunistic pathogen Pseudomonas aeruginosa PAO1 has a remarkable capacity
      to adapt to various environments and to survive with limited nutrients. Here, we
      report the discovery and characterization of a novel small non-coding RNA: NrsZ
      (nitrogen-regulated sRNA). We show that under nitrogen limitation, NrsZ is
      induced by the NtrB/C two component system, an important regulator of nitrogen
      assimilation and P. aeruginosa's swarming motility, in concert with the
      alternative sigma factor RpoN. Furthermore, we demonstrate that NrsZ modulates P.
      aeruginosa motility by controlling the production of rhamnolipid surfactants,
      virulence factors notably needed for swarming motility. This regulation takes
      place through the post-transcriptional control of rhlA, a gene essential for
      rhamnolipids synthesis. Interestingly, we also observed that NrsZ is processed in
      three similar short modules, and that the first short module encompassing the
      first 60 nucleotides is sufficient for NrsZ regulatory functions.

PMID- 24308330
TI  - A platform independent RNA-Seq protocol for the detection of transcriptome
      complexity.
AB  - BACKGROUND: Recent studies have demonstrated an unexpected complexity of
      transcription in eukaryotes. The majority of the genome is transcribed and only a
      little fraction of these transcripts is annotated as protein coding genes and
      their splice variants. Indeed, most transcripts are the result of antisense,
      overlapping and non-coding RNA expression. In this frame, one of the key aims of
      high throughput transcriptome sequencing is the detection of all RNA species
      present in the cell and the first crucial step for RNA-seq users is represented
      by the choice of the strategy for cDNA library construction. The protocols
      developed so far provide the utilization of the entire library for a single
      sequencing run with a specific platform. RESULTS: We set up a unique protocol to
      generate and amplify a strand-specific cDNA library representative of all RNA
      species that may be implemented with all major platforms currently available on
      the market (Roche 454, Illumina, ABI/SOLiD). Our method is reproducible, fast,
      easy-to-perform and even allows to start from low input total RNA. Furthermore,
      we provide a suitable bioinformatics tool for the analysis of the sequences
      produced following this protocol. CONCLUSION: We tested the efficiency of our
      strategy, showing that our method is platform-independent, thus allowing the
      simultaneous analysis of the same sample with different NGS technologies, and
      providing an accurate quantitative and qualitative portrait of complex whole
      transcriptomes.

PMID- 24308331
TI  - Novel composite material polyoxovanadate@MIL-101(Cr): a highly efficient
      electrocatalyst for ascorbic acid oxidation.
AB  - A novel hybrid composite material, PMo10V2@MIL-101 was prepared by the
      encapsulation of the tetra-butylammonium (TBA) salt of the vanadium-substituted
      phosphomolybdate [PMo10V2O40](5-) (PMo10V2) into the porous metal-organic
      framework (MOF) MIL-101(Cr). The materials characterization by powder X-ray
      diffraction, Fourier transform infrared spectra and scanning electron microscopy
      confirmed the preparation of the composite material without disruption of the MOF
      porous structure. Pyrolytic graphite electrodes modified with the original
      components (MIL-101(Cr), PMo10V2), and the composite material PMo10V2@MIL-101
      were prepared and their electrochemical responses were studied by cyclic
      voltammetry. Surface confined redox processes were observed for all the
      immobilized materials. MIL-101(Cr) showed one-electron reduction process due to
      chromium centers (Cr(III) -> Cr(II)), while PMo10V2 presented five reduction
      processes: the peak at more positive potentials is attributed to two superimposed
      1-electron vanadium reduction processes (V(V) -> V(IV)) and the other four peaks
      to Mo-centred two-electron reduction processes (Mo(VI) -> Mo(V)). The
      electrochemical behavior of the composite material PMo10V2@MIL-101 showed both
      MIL-101(Cr) and PMo10V2 redox features, although with the splitting of the two
      vanadium processes and the shift of the Mo- and Cr- centered processes to more
      negative potentials. Finally, PMo10V2@MIL-101 modified electrode showed
      outstanding enhanced vanadium-based electrocatalytic properties towards ascorbic
      acid oxidation, in comparison with the free PMo10V2, as a result of its
      immobilization into the porous structure of the MOF. Furthermore, PMo10V2@MIL-101
      modified electrode showed successful simultaneous detection of ascorbic acid and
      dopamine.

PMID- 24308332
TI  - Bilberry anthocyanins neutralize the cytotoxicity of co-chaperonin GroES
      fibrillation intermediates.
AB  - The co-chaperonin GroES (Hsp10) works with chaperonin GroEL (Hsp60) to facilitate
      the folding reactions of various substrate proteins. Upon forming a specific
      disordered state in guanidine hydrochloride, GroES is able to self-assemble into
      amyloid fibrils similar to those observed in various neurodegenerative diseases.
      GroES therefore is a suitable model system to understand the mechanism of amyloid
      fibril formation. Here, we determined the cytotoxicity of intermediate GroES
      species formed during fibrillation. We found that neuronal cell death was
      provoked by soluble intermediate aggregates of GroES, rather than mature fibrils.
      The data suggest that amyloid fibril formation and its associated toxicity toward
      cell might be an inherent property of proteins irrespective of their correlation
      with specific diseases. Furthermore, with the presence of anthocyanins that are
      abundant in bilberry, we could inhibit both fibril formation and the toxicity of
      intermediates. Addition of bilberry anthocyanins dissolved the toxic
      intermediates and fibrils, and the toxicity of the intermediates was thus
      neutralized. Our results suggest that anthocyanins may display a general and
      potent inhibitory effect on the amyloid fibril formation of various
      conformational disease-causing proteins. 

PMID- 24308333
TI  - The biggest challenges currently facing companion diagnostic advancement.
AB  - Low productivity in the pharmaceutical industry positions personalized medicine
      and companion diagnostics as an attractive approach. The oncology community is
      enthusiastic and optimistic that advances in molecular diagnostics have the
      potential to materialize the dream of personalized cancer therapy with the aim
      to: help the drug industry enhance the probability of success and, probably,
      accelerate time to market; help the diagnostics industry develop diagnostic tests
      utilizing precious human samples; and support accurate diagnosis and selection of
      the most efficacious and least toxic therapies. However, this spectacular road is
      not yet paved and remains facing the following biggest challenges: the need for
      better understanding of biology and limitations of preclinical models; pre
      analytical variables that are likely to alter results; analytical discrepancies;
      and the wide gap between clinical/pharmaceutical and diagnostic understandings.
      This article explores these challenges, their possible impacts, and provides some
      suggestions for mitigation. 

PMID- 24308334
TI  - New molecular diagnosis and screening methods for colorectal cancer using fecal
      protein, DNA and RNA.
AB  - Several screening methods for reducing the mortality rate of colorectal cancer
      (CRC) have been reported in recent decades. Fecal occult blood tests (FOBTs) are
      widely used for CRC screening and immunochemical FOBTs perform better than guaiac
      FOBTs; however, the sensitivity and specificity of immunochemical FOBTs remain
      unsatisfactory. To resolve this problem, novel fecal molecular methods based on
      fecal protein, DNA and RNA analyses have been developed. Regarding fecal
      proteins, several marker proteins indicating intestinal bleeding and cancer cell
      specific proteins have been investigated. Regarding fecal DNA, numerous gene
      mutation and gene methylation analyses have been reported. Consequently, fecal
      DNA analysis was recommended as a CRC screening method in 2008. In addition, gene
      expression analyses of CRC-specific genes and miRNAs in fecal RNA have been
      investigated over the last decade. This review article summarizes molecular
      methods using fecal samples for CRC screening, focusing on reports within the
      last 5 years. 

PMID- 24308336
TI  - Portrait Toxigenic Clostridium difficile assay, an isothermal amplification assay
      detects toxigenic C. difficile in clinical stool specimens.
AB  - The Portrait Toxigenic Clostridium difficile assay is a rapid, qualitative assay
      for the detection of the tcdB gene of C. difficile in stool specimens from
      patients suspected of C. difficile infections, and received 510(k) clearance by
      the US FDA in March 2012. The Portrait Toxigenic C. difficile assay combines
      novel blocked-primer-mediated helicase-dependent multiplex amplification (bpHDA)
      technology and chip-based detection in an automated sample-to-result format. The
      assay requires minimal sample preparation and results are available within 90
      min. In a multicenter evaluation, the Portrait Toxigenic C. difficile assay had a
      sensitivity of 98.2% and specificity of 92.8% compared with toxigenic culture. A
      comparative study between the Portrait Toxigenic C. difficile assay and three FDA
      cleared molecular assays for the detection of toxigenic C. difficile exhibited a
      high degree of agreement (93.8-97.5%). The Portrait Toxigenic C. difficile assay
      provides a simple, cost-effective method with broad applicability to panel-based
      approaches, potentially simplifying workflow. 

PMID- 24308335
TI  - DNA-based nanosensors for next-generation clinical diagnostics via detection of
      enzyme activity.
AB  - Specific and sensitive detection of DNA-modifying enzymes represents a
      cornerstone in modern medical diagnostics. Many of the currently prevalent
      methods are not preferred in the clinics because they rely heavily on pre
      amplification or post-separation steps. This editorial highlights the potential
      of adopting DNA-based nanosensors for the assessment of the activities of DNA
      modifying enzymes, with emphasis on the topoisomerase and tyrosyl-DNA
      phosphodiesterase families. By underlining the existing challenges, we expect
      that the DNA-nanosensors may soon be promoted to clinical diagnostics via enzyme
      detection. 

PMID- 24308337
TI  - The value of procalcitonin measurement in localized skin and skin structure
      infection, diabetic foot infections, septic arthritis and osteomyelitis.
AB  - Serum procalcitonin (PCT) is an established diagnostic marker for severe or
      systemic bacterial infections such as pneumonia, sepsis and septic shock. Data
      regarding the role of PCT in localized infections without systemic inflammatory
      response syndrome are scarce. The aim of this review is to assess the value of
      PCT measurements in localized infections such as skin and skin structure
      infections, diabetic foot infections, septic arthritis (SA) and osteomyelitis. It
      appears that serum PCT is unlikely to change the clinical practice in skin and
      skin structure infection. However, serum PCT could have a role in diagnosis and
      monitoring of diabetic foot infections in hospitalized settings. There are
      conflicting reports regarding the ability of serum PCT to distinguish SA from non
      SA; synovial PCT may be more appropriate in these settings, including in implant
      related infections. Better designed studies are needed to evaluate the usefulness
      of PCT with or without other biomarkers in localized infections. 

PMID- 24308339
TI  - Serum free light chain analysis in the diagnosis and management of multiple
      myeloma and related conditions.
AB  - The serum free light chain (FLC) assay is an important tool in the management of
      patients with monoclonal gammopathies. MEDLINE, the Cochrane Central Register of
      Controlled Trials and the Cochrane Database of Systematic Reviews from January
      2000 through July 2013, were used as data sources. The available evidence is
      rather weak. For screening of multiple myeloma and related conditions, the
      association of the FLC assay with the traditional serum tests avoids urine study.
      Screening for immunoglobulin light-chain (AL) amyloidosis or other rare syndromes
      requires the urine examination. FLC measurement is used in the assessment of the
      risk of progression of precursor diseases to overt myeloma, and for risk
      stratification in solitary plasmacytoma, multiple myeloma and AL amyloidosis. In
      patients with oligosecretory myeloma and AL amyloidosis, the quantification of
      FLC is essential for monitoring and categorization of response to therapy.
      Further studies with improved design are warranted to strengthen the available
      evidence.

PMID- 24308340
TI  - The application of monoclonal antibodies in cancer diagnosis.
AB  - Cancer becomes the second leading cause of death in the world. An effective
      strategy for early diagnosis of the disease is key to reduce the mortality and
      morbidity. Development of effective monoclonal antibody (mAb)-based assays or
      diagnostic imaging techniques for detection of antigens and small molecules that
      are released from cancerous cells will enhance modern diagnostic medicine of
      cancer significantly. Although mAb technology is still under development, recent
      advances in preparation of recombinant antigen and antibody engineering
      techniques have dramatically enhanced the applications of this technology in
      cancer diagnosis. Compared with other methods, mAb-based assays may provide
      spatial, temporal, accurate and quantitative measurement for diagnosis of the
      disease. This review summarizes the progress of the mAb-based assays in the field
      of molecular diagnosis of cancer. 

PMID- 24308341
TI  - cobas 4800 HPV Test, a real-time polymerase chain reaction assay for the
      detection of human papillomavirus in cervical specimens.
AB  - Cervical cancer screening incorporating high-risk human papillomavirus (HPV)
      detection has become the preferred screening strategy in some countries and is
      increasingly more widespread in other countries with organized or opportunistic
      screening programs. Given knowledge that high-risk HPV genotypes differ in their
      oncogenic potential, commercial HPV assays with genotyping capabilities have been
      developed and have garnered attention in the recent literature. The cobas 4800
      HPV Test is a qualitative multiplex assay that provides specific genotyping
      information for HPV types 16 and 18, while concurrently detecting 12 other high
      risk HPV genotypes as a pooled result. It is currently the only clinically
      validated, US FDA-approved assay with this capability. Since HPV types 16 and 18
      have been designated as conferring the greatest risk for cervical disease, their
      detection may prove useful in guiding patient management.

PMID- 24308342
TI  - Coupling of soil solarization and reduced rate fumigation: effects on methyl
      iodide emissions from raised beds under field conditions.
AB  - Using field plots, we studied the effect on methyl iodide (MeI) emissions of
      coupling soil solarization (passive and active) and reduced rate fumigation (70%
      of a standard fumigation) in raised beds under virtually impermeable film (VIF).
      The results showed that for the standard fumigation and the passive solarization
      + fumigation treatments, emissions from the nontarped furrow were very high
      (~50%). Emissions from the bed top and sidewall of these treatments were
      relatively low but were increased in the latter due to the longer environmental
      exposure of the VIF covering with the coupled approach (increased tarp
      permeability). Overall, this approach offered no advantage over fumigation-only
      in terms of emission reduction. With active solarization + fumigation, the large
      application of hot water during solarization apparently led to severely limited
      diffusion causing very low total emissions (<1%). Although this suggests a
      benefit in terms of air quality, a lack of diffusion could limit the pesticidal
      efficacy of the treatment. 

PMID- 24308344
TI  - Patients with Korsakoff syndrome in nursing homes: characteristics, comorbidity,
      and use of psychotropic drugs.
AB  - BACKGROUND: Very limited literature exists on the care and course of patients
      with Korsakoff syndrome (KS) living in long-term care facilities (LTCFs). Even
      less literature can be found on the pharmacological treatment of behavioral
      symptoms of KS. The purpose of the present study was to describe baseline
      characteristics, comorbidity, and the use of psychotropic drugs in
      institutionalized patients with KS. METHODS: In this cross-sectional descriptive
      study, 556 patients were included living in ten specialized care units in Dutch
      nursing homes. Data were collected by means of a retrospective chart review.
      RESULTS: The majority of patients were men (75%) and single (78%) with a mean age
      on admission of 56.7 years (SD 8.9, range 29.8-85.3). Mean length of stay was 6.0
      years (SD 5.4, range 0.2-33.3). Sixty-eight percent of patients suffered from at
      least one somatic disease and 66% from at least one extra psychiatric disorder.
      One or more psychotropic drugs were prescribed to 71% of patients with a great
      variation in prescription patterns between the different nursing homes.
      CONCLUSION: Patients with KS depending on long-term care usually have comorbidity
      in more than one domain (somatic and psychiatric). The indications for
      prescribing psychotropic drugs are in many cases unclear and it seems probable
      that they are often given to manage challenging behavior. Longitudinal studies on
      the evidence for this prescription behavior and possible alternatives are
      recommended.

PMID- 24308345
TI  - Dibromoisobenzofuran as a formal equivalent of didehydroisobenzofuran: reactive
      platform for expeditious assembly of polycycles.
AB  - Two-directional annulation of dibromoisobenzofuran, a formal equivalent to
      didehydroisobenzofuran, was developed. Importantly, selective bromine-lithium
      exchange allows the tandem generation of benzynes and dual cycloadditions with
      two different arynophiles. Also described is the application to the synthesis of
      a substituted pentacene. 

PMID- 24308343
TI  - A synergistic approach towards understanding the functional significance of
      dopamine receptor interactions.
AB  - The importance of the neurotransmitter dopamine (DA) in the nervous system is
      underscored by its role in a wide variety of physiological and neural functions
      in both vertebrates and invertebrates. Binding of dopamine to its membrane
      receptors initiates precise signaling cascades that result in specific cellular
      responses. Dopamine receptors belong to a super-family of G-protein coupled
      receptors (GPCRs) that are characterized by seven trans-membrane domains. In
      mammals, five dopamine receptors have been identified which are grouped into two
      different categories D1- and D2-like receptors. The interactions of DA receptors
      with other proteins including specific Galpha subunits are critical in deciding
      the fate of downstream molecular events carried out by effector proteins. In this
      mini-review we provide a synopsis of known protein-protein interactions of DA
      receptors and a perspective on the potential synergistic utility of
      Caenorhabditis elegans as a model eukaryote with a comparatively simpler nervous
      system to gain insight on the neuronal and behavioral consequences of the
      receptor interactions. 

PMID- 24308346
TI  - Estimating the lifelong health impact and financial burdens of different types of
      lung cancer.
AB  - BACKGROUND: Owing to the high mortality and rapidly growing costs related to lung
      cancer, it is worth examining the health benefits of prevention for major types
      of lung cancer. This study attempts to quantify the quality-adjusted life
      expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures of patients
      with different pathological types of lung cancer. METHODS: A national cohort
      consisting of 66,535 patients with pathologically verified lung cancer was
      followed for 13 years (1998-2010) to obtain the survival function, which was
      further extrapolated to lifetime. Between 2011 and 2012, EuroQol 5-dimension
      questionnaires were used to measure the quality of life (QoL) for 1,314
      consecutive, cross-sectional samples. After multiplying the lifetime survival
      function by the utility values of QoL, we estimated the QALE and loss-of-QALE. We
      also collected the monthly healthcare expenditures, which included National
      Health Insurance-reimbursed and out-of-pocket direct medical costs, for 2,456
      patients from 2005 to 2012. These values were multiplied by the corresponding
      survival probabilities to calculate lifetime healthcare expenditures after
      adjustments with medical care inflation rates and annual discount rates. RESULTS:
      The QALE for patients with small cell lung cancer, squamous cell carcinoma, and
      adenocarcinoma were 1.21, 2.37, and 3.03 quality-adjusted life year (QALY), with
      the corresponding loss-of-QALE of 13.69, 12.22, and 15.03 QALY, respectively. The
      lifetime healthcare expenditures were US$ 18,455 +/- 1,137, 20,599 +/- 1,787, and
      36,771 +/- 1,998, respectively. CONCLUSIONS: The lifelong health impact and
      financial burdens in Taiwan are heavier for adenocarcinoma than for squamous cell
      carcinoma. The cost-effectiveness of prevention programs could be directly
      compared with that of treatment strategies to improve patient value. And the
      methodology could be applied to other chronic diseases for resources planning of
      healthcare services.

PMID- 24308347
TI  - Paper-based microfluidic device with upconversion fluorescence assay.
AB  - A paper-based microfluidic device with upconversion fluorescence assay (named as
      UC-MUPAD) is proposed. The device is fabricated on a normal office printing sheet
      with a simple plotting method. Upconversion phosphors (UCPs) tagged with specific
      probes are spotted to the test zones on the MUPAD, followed by the introduction
      of assay targets. Upconversion fluorescence measurements are directly conducted
      on the test zones after the completion of the probe-to-target reactions, without
      any post-treatments. The UC-MUPAD features very easy fabrication and operation,
      simple and fast detection, low cost, and high sensitivity. UC-MUPAD is a
      promising prospect for a clinical point-of-care test. 

PMID- 24308348
TI  - A general approach for predicting the filtration of soft and permeable colloids:
      the milk example.
AB  - Membrane filtration operations (ultra-, microfiltration) are now extensively used
      for concentrating or separating an ever-growing variety of colloidal dispersions.
      However, the phenomena that determine the efficiency of these operations are not
      yet fully understood. This is especially the case when dealing with colloids that
      are soft, deformable, and permeable. In this paper, we propose a methodology for
      building a model that is able to predict the performance (flux, concentration
      profiles) of the filtration of such objects in relation with the operating
      conditions. This is done by focusing on the case of milk filtration, all
      experiments being performed with dispersions of milk casein micelles, which are
      sort of "natural" colloidal microgels. Using this example, we develop the general
      idea that a filtration model can always be built for a given colloidal dispersion
      as long as this dispersion has been characterized in terms of osmotic pressure Pi
      and hydraulic permeability k. For soft and permeable colloids, the major issue is
      that the permeability k cannot be assessed in a trivial way like in the case for
      hard-sphere colloids. To get around this difficulty, we follow two distinct
      approaches to actually measure k: a direct approach, involving osmotic stress
      experiments, and a reverse-calculation approach, that consists of estimating k
      through well-controlled filtration experiments. The resulting filtration model is
      then validated against experimental measurements obtained from combined milk
      filtration/SAXS experiments. We also give precise examples of how the model can
      be used, as well as a brief discussion on the possible universality of the
      approach presented here. 

PMID- 24308349
TI  - Economic valuation of informal care in cerebrovascular accident survivors in
      Spain.
AB  - BACKGROUND: Cerebrovascular diseases are the second leading cause of death
      worldwide and one of the health conditions which demand the highest level of
      social services. The aim of this study was to estimate the social cost of non
      professional (informal) care provided to survivors of cerebrovascular accidents
      (CVA) with some type of disability in Spain. METHODS: We obtained data from the
      2008 Survey on Disability, Independent Living and Dependency (EDAD-08) on the
      main characteristics of individuals who provide informal care to survivors of
      CVAs in Spain. We estimated the cost of substituting informal care in favor of
      formal care provided by professional caregivers (proxy good method) and performed
      a statistical analysis of the relationship between degree of dependency and
      number of care hours provided using ordinary least squares regression. RESULTS:
      The number of disabled people diagnosed with CVA totaled 1,975 (329,544 people
      when extrapolating to the national population using the elevation factor provided
      by EDAD-08). Of these, 1,221 individuals (192,611 people extrapolated to the
      national population) received at least one hour of informal care per week. The
      estimated hours of informal care provided in 2008 amounted to 852 million. The
      economic valuation of the time of informal care ranges from 6.53 billion euros
      (at 7.67 euros/hour) to 10.83 billion euros (when calculating each hour of care
      at 12.71 euros). The results of our statistical analysis highlight the importance
      of degree of dependency in explaining differences in the number of hours of
      informal care provided. CONCLUSIONS: The results of our study reveal the high
      social cost of cerebrovascular accidents in Spain. In addition, evidence is
      presented of a correlation between higher degree of dependency in CVA survivors
      and greater number of hours of care received. An integral approach to care for
      CVA survivors requires that the caregivers' role and needs be taken into account.

PMID- 24308350
TI  - Particle size-specific distributions and preliminary exposure assessments of
      organophosphate flame retardants in office air particulate matter.
AB  - In this study, the concentrations, size-specific distributions, and preliminary
      exposure assessments of 10 organophosphate flame retardants (OPFRs) were
      investigated in suspended particulate matter collected from offices. OPFRs were
      detected in a range of 5.00-147.77 ng/m(3). Tri(chloropropyl) phosphate (TCPP)
      was the most abundant analog followed by tri(2-chloroethyl) phosphate (TCEP) and
      triphenyl phosphate (TPhP). Chlorinated OPFRs (TCPP, TCEP, and tris(1,3
      dichloroisopropyl) phosphate (TDCPP)) contributed to about 77% of the total
      OPFRs. Size-specific distributions revealed that TCEP, tri-n-propyl phosphate
      (TnPP), TCPP, and tri-n-butyl phosphate (TnBP) shared a similar distribution
      pattern with a peak in the fraction 4.7-5.8 MUm. A peak was also found in the
      distributions of tricresyl phosphate (TCrP), 2-ethylhexyl diphenyl phosphate
      (EHDPP), and tri(2-ethylhexyl) phosphate (TEHP) but in different fractions. A
      bimodal distribution was observed for TDCPP, TPhP, and tributoxyethyl phosphate
      (TBEP). The results of mass median aerodynamic diameter (MMAD) indicated that
      TDCPP, TCrP, and TEHP were mainly located on ultrafine particles (<=1 MUm), while
      TnPP, TBEP, and EHDPP mainly on fine particles (<=2.5 MUm). Furthermore, MMADs of
      OPFRs were found to be positively correlated with their vapor pressures (Vp) (p <
      0.01), indicating that OPFR analogs with low Vp were inclined to adsorb on small
      size particles. Preliminary exposure assessments suggested a low risk of exposure
      to OPFRs for people working in such offices, and inhaled OPFRs would mainly
      deposit in the head region of the respiratory tract. 

PMID- 24308351
TI  - Protective effects of dietary PUFA against chronic disease: evidence from
      epidemiological studies and intervention trials.
AB  - This review considers evidence for a protective effect of PUFA on chronic
      disease. Estimates of PUFA intakes in prospective cohort studies are usually
      based on FFQ or biomarkers of intake. Cohort studies suggest that both linoleic
      and linolenic acid intake are associated with a lower risk of CHD. The intake of
      fish, the major source of long-chain n-3 PUFA is associated with a lower risk of
      both stroke and CHD, particularly sudden cardiac death. No relationship with
      common sites of cancer (breast and colon) and PUFA has been found. However, some
      recent studies suggest an association of high intakes of n-3 PUFA with risk of
      prostate cancer. An updated Cochrane review of dietary fat modification
      (replacing SFA with PUFA) randomised controlled trials to prevent CHD found a 14%
      lower incidence and a non-significant 7% lower mortality from CHD. The effects of
      an increased intake of n-3 PUFA on CHD incidence mortality have been tested in
      patients with pre-existing CHD in randomised controlled trials. Meta-analysis of
      these trials showed no overall benefit on total mortality or CVD incidence but a
      trend for lower risk of cardiac death was 0.91 (95% CI 0.85, 0.98). At present,
      there is little evidence from other trials demonstrating the clear benefits or
      harm from increased intakes of PUFA. In conclusion, present evidence intakes
      benefit from partial replacement of SFA with a balanced mixture of n-6 and n-3
      PUFA which may contribute to CVD prevention.

PMID- 24308353
TI  - The attachment affinity of hemoglobin toward silver-containing bioactive glass
      functionalized with glutaraldehyde.
AB  - Bioactive glasses belonging to the 56SiO2.(40 - x)CaO.4P2O5.xAg2O system, with x
      = 0, 2, and 8 mol %, were surface functionalized with the protein coupling agent
      glutaraldehyde (GA) and further evaluated in terms of hemoglobin affinity. The
      bare and GA-functionalized samples were investigated before and after protein
      attachment, by electron paramagnetic resonance (EPR) spectroscopy combined with
      spin-labeling procedure. Methanethiosulfonate spin label was used to explore the
      local environment of beta-93 cysteine in horse hemoglobin, in terms of spin label
      side chain mobility. The EPR simulation methods were employed to quantify the
      rotational correlational times and fraction of the immobilized spin labels. The
      EPR absorption spectrum was further exploited to estimate the amount of
      hemoglobin loaded on the substrates. The surface elemental composition obtained
      by X-ray photoelectron spectroscopy revealed similar tendency in terms of surface
      coverage. Changes in surface architecture, that is, changes in surface morphology
      after protein coverage, were observed by scanning electron microscopy. It was
      concluded that GA improves the stability of protein attachment and induces
      polymerization of hemoglobin molecules. 

PMID- 24308352
TI  - Isometric exercise as a test of pain modulation: effects of experimental pain
      test, psychological variables, and sex.
AB  - OBJECTIVE: Little is known regarding whether exercise-induced hypoalgesia (EIH)
      produced by isometric exercise is influenced by psychological factors or
      systematically varies across multiple experimental psychophysical pain tests.
      Thus, this study sought to determine the influence of experimental pain test,
      psychological factors, and sex on the hypoalgesic response of submaximal
      isometric exercise. METHODS: Healthy young males (N = 12) and females (N = 15)
      completed one training and two testing sessions consisting of quiet rest (control
      condition) or a 3-minute isometric handgrip performed at 25% of maximum voluntary
      contraction. Pain testing was conducted on both forearms prior to and following
      exercise and quiet rest. The pain tests included: pressure pain thresholds (PPT),
      suprathreshold pressure pain test, static prolonged heat test, and temporal
      summation of heat pain. Participants completed the Pain Catastrophizing Scale
      during the training session and the State-Trait Anxiety Inventory-State version
      prior to each session. The data were analyzed with mixed model analyses of
      variance, partial Pearson correlations, and hierarchical regression analyses.
      RESULTS: Isometric exercise increased PPTs for men and women, reduced pain
      perception during static prolonged heat stimuli for women, and reduced temporal
      summation of pain for men and women. Greater pain catastrophizing was associated
      with smaller reductions in temporal summation following isometric exercise.
      CONCLUSIONS: These findings demonstrate that the hypoalgesic response to
      submaximal isometric exercise is partially a function of sex and experimental
      pain test. Furthermore, the relationship between EIH and pain catastrophizing was
      psychophysical pain test specific, with greater pain catastrophizing predicting
      diminished EIH only during the temporal summation of pain trials.

PMID- 24308354
TI  - The conditional importance of sex: exploring the association between sexual well
      being and life satisfaction.
AB  - Leaders in the field of sexuality have called for additional research examining
      the link between sexual well-being and life satisfaction in women in order to
      expand knowledge regarding the important consequences of a satisfying sex life.
      Participants in the present study were sexually active women reporting a wide
      range of sexual difficulties who completed an in-person interview, validated self
      report measures, and daily online assessments for 4 weeks. Sexual well-being was
      related to life satisfaction both cross-sectionally and within individuals over
      time. In addition, high relational satisfaction and low attachment anxiety served
      as protective factors, decreasing the degree to which unsatisfying sexual
      experiences were associated with decreases in life satisfaction. These results
      extend previous findings by confirming a strong association between sexual well
      being and overall life satisfaction within individuals over time. The strength of
      this association is moderated by a number of intra- and interpersonal factors.
      Implications for healthcare providers are discussed. 

PMID- 24308355
TI  - Public-private partnerships to revitalize psychiatric drug discovery.
AB  - INTRODUCTION: Precompetitive public-private partnerships (PPPs) have the
      potential to improve psychiatric drug discovery by addressing gaps in the
      research and development pipeline such as the identification and validation of
      new targets, models, biomarkers and disease phenotyping. PPPs are a model to
      strategically bring together expertise, in-kind support and funding from multiple
      public and private sector partners. AREAS COVERED: This editorial describes
      selected case examples of established and emerging public-private consortia in
      the United States and Europe that provide tools, methods or resources to
      accelerate central nervous system (CNS) drug discovery. The authors provides a
      listing of public-private consortia projects that focus on the CNS, the stage of
      the drug discovery pipeline that they address, diseases, deliverables provided
      and current consortia partners. EXPERT OPINION: Some of the projects undertaken
      by PPPs in the area of CNS drug discovery and development are beginning to make
      tools, resources and data publicly available. Only a few PPPs have delivered
      enough to extract lessons learned. These include building alignment across a wide
      group of stakeholders, engaging advocacy groups and funding commitments for a
      minimum of 5 years.

PMID- 24308356
TI  - Nocturnal continuous positive airway pressure in severe non-apneic asthma. A
      pilot study.
AB  - INTRODUCTION: It has been demonstrated that brief periods of nocturnal continuous
      positive airway pressure (nCPAP) reduce airway reactivity in animal models and in
      patients with asthma. The effects of nCPAP in severe uncontrolled non-apneic
      asthmatic patients are not well known. AIM: In this open pilot study, we aimed to
      assess the effect nCPAP on peak flow (PEF) variability and asthma control in this
      type of patients. METHODS: CPAP was applied to 10 patients with severe long
      standing asthma without obstructive sleep apnea for seven consecutive nights.
      CPAP was titrated in auto setting and applied to the patients. Daily PEF, was
      measured from 2 weeks before the intervention to 2 weeks after the end of nCPAP
      treatment. PEF amplitude and PEF morning dip (MD) over 24-h periods averaged over
      1 week were calculated as indexes of PEF variability. Asthma control test (ACT)
      and European quality of life (EuroQol) questionnaire were measured at baseline
      and after 1 month, and at baseline and at the end of CPAP period, respectively.
      RESULTS: The PEF amplitude significantly decreased both during CPAP period and in
      the first week after nCPAP discontinuation as compared with the baseline (19.8 +/
      7.5%, 23.9 +/- 9.1% and 28.9 +/- 11.5%, respectively, always P < 0.05). PEF MD
      significantly decreased during nCPAP in comparison with the baseline (P < 0.001).
      The ACT and EuroQol significantly improved after nCPAP in comparison with the
      basal value. CONCLUSIONS: In this preliminary report, brief period of nCPAP
      reduces PEF variability and improves control in severe non-apneic asthma at a
      short-term evaluation. Further studies with longer-term evaluation and larger
      number of patients are warranted.

PMID- 24308357
TI  - Acute effect of carbamazepine on corticothalamic 5-9-Hz and thalamocortical
      spindle (10-16-Hz) oscillations in the rat.
AB  - A major side effect of carbamazepine (CBZ), a drug used to treat neurological and
      neuropsychiatric disorders, is drowsiness, a state characterized by increased
      slow-wave oscillations with the emergence of sleep spindles in the
      electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular
      recordings in freely moving or lightly anesthetized rats to explore the impact of
      CBZ within the intact corticothalamic (CT)-thalamocortical (TC) network, more
      specifically on CT 5-9-Hz and TC spindle (10-16-Hz) oscillations. Two to three
      successive 5-9-Hz waves were followed by a spindle in the cortical EEG. A single
      systemic injection of CBZ (20 mg/kg) induced a significant increase in the power
      of EEG 5-9-Hz oscillations and spindles. Intracellular recordings of
      glutamatergic TC neurons revealed 5-9-Hz depolarizing wave-hyperpolarizing wave
      sequences prolonged by robust, rhythmic spindle-frequency hyperpolarizing waves.
      This hybrid sequence occurred during a slow hyperpolarizing trough, and was at
      least 10 times more frequent under the CBZ condition than under the control
      condition. The hyperpolarizing waves reversed at approximately -70 mV, and became
      depolarizing when recorded with KCl-filled intracellular micropipettes,
      indicating that they were GABAA receptor-mediated potentials. In neurons of the
      GABAergic thalamic reticular nucleus, the principal source of TC GABAergic
      inputs, CBZ augmented both the number and the duration of sequences of rhythmic
      spindle-frequency bursts of action potentials. This indicates that these
      GABAergic neurons are responsible for the generation of at least the spindle
      frequency hyperpolarizing waves in TC neurons. In conclusion, CBZ potentiates
      GABAA receptor-mediated TC spindle oscillations. Furthermore, we propose that CT
      5-9-Hz waves can trigger TC spindles.

PMID- 24308358
TI  - Role of toll-like receptors gene polymorphism in renal transplantation.
AB  - Toll-like receptors (TLRs), evolutionarily conserved innate, are expressed in a
      wide variety of tissues and cell types, and they play key role in the innate
      immune system. Gene mutation is an important factor associated with some diseases
      risk and gene polymorphism of TLRs can influence their function to take part in
      the physiological process in the body. Chronic kidney disease causes high
      morbidity and mortality, and renal transplantation provides the optimal treatment
      for people with end-stage renal disease. Innate immune takes a most important
      role in renal transplantation. There are some studies reporting that TLRs gene
      polymorphism takes an important role in the renal transplantation. However, no
      review summed up the role of TLRs gene polymorphism in renal transplantation. The
      literatures were searched extensively and this review was performed to review the
      role of TLRs gene polymorphism in renal transplantation.

PMID- 24308359
TI  - Electronic health records for biological sample collection: feasibility study of
      statin-induced myopathy using the Clinical Practice Research Datalink.
AB  - AIMS: Electronic healthcare records (EHRs) are increasingly used to store
      clinical information. A secondary benefit of EHRs is their use, in an anonymized
      form, for observational research. The Clinical Practice Research Datalink (CPRD)
      contains EHRs from primary care in the UK and, despite 1083 peer-reviewed
      research publications, has never been used to obtain pharmacogenetic samples.
      Using a statin-induced myopathy paradigm, we evaluated using the CPRD to obtain
      patient samples for a pharmacogenetic study targeting 250 cases and 500 controls
      from UK general practitioner (GP) practices. METHODS: The CPRD identified
      potential patients fitting specific case-definition criteria (active
      rhabdomyolysis or creatine phosphokinase > four times the upper limit of normal),
      and corresponding GP practices were asked to invite patient participation.
      Consenting patients were requested to provide either saliva or blood samples and
      to complete an ethnicity questionnaire. Control subjects were recruited from the
      same GP practice (saliva) or a small number of practices (blood). Samples were
      forwarded for DNA extraction. RESULTS: Thirty-six months of recruitment yielded
      DNA samples from 149 statin-induced myopathy cases and 587 tolerant controls.
      Data show that contacting patients through their GP is a reliable method for
      obtaining samples without compromising anonymity. Saliva collection directly from
      patients was considerably less effective than blood sampling. After 10 months of
      recruitment, saliva sampling was suspended in favour of blood sampling.
      CONCLUSIONS: We demonstrate the potential of EHRs for identifying accurately
      phenotyped cases and controls for pharmacogenetic studies. Recruitment was
      successful only because of the willingness of GP practices to participate and the
      existence of strong doctor-patient relationships. The present study provides a
      model that can be implemented in future genetic analyses using EHRs.

PMID- 24308360
TI  - Biosynthesis of the active compounds of Isatis indigotica based on transcriptome
      sequencing and metabolites profiling.
AB  - BACKGROUND: Isatis indigotica is a widely used herb for the clinical treatment of
      colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various
      structural classes of compounds have been identified as effective ingredients.
      However, little is known at genetics level about these active metabolites. In the
      present study, we performed de novo transcriptome sequencing for the first time
      to produce a comprehensive dataset of I. indigotica. RESULTS: A database of
      36,367 unigenes (average length = 1,115.67 bases) was generated by performing
      transcriptome sequencing. Based on the gene annotation of the transcriptome, 104
      unigenes were identified covering most of the catalytic steps in the general
      biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently,
      the organ-specific expression patterns of the genes involved in these pathways,
      and their responses to methyl jasmonate (MeJA) induction, were investigated.
      Metabolites profile of effective phenylpropanoid showed accumulation pattern of
      secondary metabolites were mostly correlated with the transcription of their
      biosynthetic genes. According to the analysis of UDP-dependent
      glycosyltransferases (UGT) family, several flavonoids were indicated to exist in
      I. indigotica and further identified by metabolic profile using UPLC/Q-TOF.
      Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs
      were suggested as flavonol glycosyltransferases and lignan glycosyltransferases.
      CONCLUSIONS: This database provides a pool of candidate genes involved in
      biosynthesis of effective metabolites in I. indigotica. Furthermore, the
      comprehensive analysis and characterization of the significant pathways are
      expected to give a better insight regarding the diversity of chemical
      composition, synthetic characteristics, and the regulatory mechanism which
      operate in this medical herb.

PMID- 24308361
TI  - Expression of a single-chain human leukocyte antigen-DRA/DRB3*01:01 molecule and
      differential binding of a monoclonal antibody in the presence of specifically
      bound human platelet antigen-1a peptide.
AB  - BACKGROUND: Studies show that 1 in 1200 neonates have a low platelet (PLT) count
      due to alloimmunization against human PLT antigen (HPA)-1a (beta3 -L33). This
      mainly occurs in HPA-1a-negative mothers who are positive for the human leukocyte
      antigen (HLA)-DRB3*01:01 allele, but only about one-third of cases will mount an
      effective alloimmune response. The development of specific treatment modalities
      requires that the mechanisms driving the maternal alloimmune response against the
      fetal PLTs be further explored. An antibody reagent that has a different binding
      affinity to HLA-DRA/DRB3*01:01 with and without the beta3 -L33 peptide would be a
      valuable reagent to study peptide presentation on maternal antigen-presenting
      cells. STUDY DESIGN AND METHODS: To identify such antibodies, HLA-DRA/DRB3*01:01
      was recombinantly expressed in Drosophila S2 cells. To delineate the epitope of
      interesting antibodies, seven mutant HLA-DRA/DRB3*01:01 molecules were generated
      by site-directed mutagenesis introducing naturally occurring amino acid changes
      encoded by DRB3*02 and DRB3*03 alleles. RESULTS: The murine monoclonal antibody
      (MoAb) DA2 showed robust binding by enzyme-linked immunosorbent assay to
      recombinant HLA-DRA/DRB3*01:01, but binding was reduced in the presence of beta3 
      L33 peptide. The binding affinity of DA2 to the mutant HLA-DRA/DRB3*0101 in which
      serine at Position 60 of the beta1-chain was replaced by tyrosine was greatly
      enhanced. Interestingly the binding of DA2 to the mutant was not reduced by the
      presence of beta3 -L33 peptide. CONCLUSION: The results of this study generate a
      molecular model of the interaction of the HLA-DRA/DRB3*01:01 molecule with MoAb
      DA2. This will inform functional studies with the recombinant Class II molecules.

PMID- 24308362
TI  - Recent advancements of flow cytometry: new applications in hematology and
      oncology.
AB  - Flow cytometry offers great diagnostic opportunities in the vast majority of
      hematologic and oncologic diseases with multiple cellular and molecular
      information within an individual cell. We will discuss various applications of
      flow cytometry, particularly in hematology and oncology, in addition to general
      principles and limitations of flow cytometry. They include nucleic acid analyses
      in cancer cells, new methods for assessing rare circulating tumor cells and
      disease-specific applications in malignancy with emphasis on diagnosis and
      treatment of hematologic malignancy, including minimal residual disease. With
      improvement of monoclonal antibodies, fluorescence and laser technology, flow
      cytometry now offers new avenues of assessing cellular functionality through
      examination of intracellular compartments. High-throughput quantitative analysis,
      advancements of in vivo flow cytometry and assessment of minimal residual
      diseases, as exampled in patient stratification and prediction of leukemia
      therapeutic response, will further make flow cytometry indispensable in medicine.

PMID- 24308363
TI  - O-methylated theaflavins suppress the intracellular accumulation of triglycerides
      from terminally differentiated human visceral adipocytes.
AB  - A known O-methylated theaflavin, theaflavin 3-O-(3-O-methyl)gallate (3MeTF3G),
      and the new theaflavin 3-O-(3,5-di-O-methyl)gallate (3,5diMeTF3G) were
      synthesized via the O-methylation of theaflavin 3-O-gallate (TF3G). Both 3MeTF3G
      and 3,5diMeTF3G are more stable than TF3G at pH 7.5 in the order 3,5diMeTF3G >
      3MeTF3G > TF3G. The inhibitory effects of these compounds on the intracellular
      accumulation of triglycerides from terminally differentiated human visceral
      adipocytes were investigated. Compound 3MeTF3G exhibited an inhibitory effect
      similar to that of TF3G at 3 MUM and a slightly lower effect than that of TF3G at
      10 MUM. The result suggested that the degradants and oxidatively polymerized
      products of TF3G may also have inhibitory effects. For cells treated with
      3,5diMeTF3G at 3 and 10 MUM, intracellular triglyceride accumulation was dose
      dependent and significantly lower compared with that for other compounds. It was
      suggested that the higher effect of 3,5diMeTF3G was due to its higher stability
      and likely improved absorption owing to di-O-methylation. 

PMID- 24308364
TI  - Assessing the in vivo efficacy of doxorubicin loaded hyaluronan nanoparticles.
AB  - Magnetic nanoparticles are attractive platforms for biomedical applications
      including diagnosis and treatment of diseases. We have shown previously that
      hyaluronan-coated superparamagnetic iron oxide nanoparticles (HA-SPIONs) enhanced
      the efficacy of the conjugated anticancer drug doxorubicin (DOX) in vitro against
      drug-sensitive and drug-resistant human ovarian cancer cells. In this manuscript,
      we report our findings on the efficacy of DOX loaded HA-SPIONs in vivo using
      subcutaneous and intraperitoneal SKOV-3 ovarian tumor models in nude mice. The
      accumulation of the nanoparticles in subcutaneous tumors following an intravenous
      nanoparticle administration was confirmed by magnetic resonance imaging, and its
      distribution in the tumors was evaluated by confocal microscopy and Prussian blue
      staining. DOX delivered by nanoparticles accumulated at much higher levels and
      distributed wider in the tumor tissue than intravenously injected free DOX,
      leading to significant reduction of tumor growth. The IVIS Spectrum for in vivo
      bioluminescence imaging was used to aid in therapy assessment of the DOX-loaded
      nanoparticles on intraperitoneal ovarian tumors formed by firefly luciferase
      expressing human ovarian SKOV-3 cells. DOX-loaded HA-SPIONs significantly reduced
      tumor growth, delayed tumor development, and extended the survival of mice. Thus,
      utilizing HA-SPIONs as drug delivery vehicles constitutes a promising approach to
      tackle CD44 expressing ovarian cancer. 

PMID- 24308365
TI  - A multi-level multi-scale approach to study essential genes in Mycobacterium
      tuberculosis.
AB  - BACKGROUND: The set of indispensable genes that are required by an organism to
      grow and sustain life are termed as essential genes. There is a strong interest
      in identification of the set of essential genes, particularly in pathogens, not
      only for a better understanding of the pathogen biology, but also for identifying
      drug targets and the minimal gene set for the organism. Essentiality is
      inherently a systems property and requires consideration of the system as a whole
      for their identification. The available experimental approaches capture some
      aspects but each method comes with its own limitations. Moreover, they do not
      explain the basis for essentiality in most cases. A powerful prediction method to
      recognize this gene pool including rationalization of the known essential genes
      in a given organism would be very useful. Here we describe a multi-level multi
      scale approach to identify the essential gene pool in a deadly pathogen,
      Mycobacterium tuberculosis. RESULTS: The multi-level workflow analyses the
      bacterial cell by studying (a) genome-wide gene expression profiles to identify
      the set of genes which show consistent and significant levels of expression in
      multiple samples of the same condition, (b) indispensability for growth by using
      gene expression integrated flux balance analysis of a genome-scale metabolic
      model, (c) importance for maintaining the integrity and flow in a protein-protein
      interaction network and (d) evolutionary conservation in a set of genomes of the
      same ecological niche. In the gene pool identified, the functional basis for
      essentiality has been addressed by studying residue level conservation and the
      sub-structure at the ligand binding pockets, from which essential amino acid
      residues in that pocket have also been identified. 283 genes were identified as
      essential genes with high-confidence. An agreement of about 73.5% is observed
      with that obtained from the experimental transposon mutagenesis technique. A
      large proportion of the identified genes belong to the class of intermediary
      metabolism and respiration. CONCLUSIONS: The multi-scale, multi-level approach
      described can be generally applied to other pathogens as well. The essential gene
      pool identified form a basis for designing experiments to probe their finer
      functional roles and also serve as a ready shortlist for identifying drug
      targets.

PMID- 24308367
TI  - Submicrometer-sized hierarchical hollow spheres of heavy lanthanide
      orthovanadates: sacrificial template synthesis, formation mechanism, and
      luminescent properties.
AB  - Hollow spheres of heavy lanthanide orthovanadates (LnVO4, Ln = Tb, Dy, Er, Tm,
      Yb, Lu) and yolk-shell structures of Ho(OH)CO3@HoVO4 have been successfully
      prepared by employing Ln(OH)CO3 colloidal spheres as a sacrificial template and
      NH4VO3 as a vanadium source. In particular, the as-obtained LuVO4 hollow spheres
      are assembled from numerous hollow-structured elliptic nanoparticles, and their
      textural parameters such as the inner and outer diameters, shell thicknesses, and
      number of shells could be finely tuned through introducing different amounts of
      NH4VO3 and employing Lu(OH)CO3 templates with different sizes. The possible
      mechanisms for the formation of hollow spheres and yolk-shell structures, and
      also the hollow-structured elliptic nanoparticles of LuVO4, i.e., building blocks
      of LuVO4 hollow spheres, are proposed and discussed in detail. Under ultraviolet
      excitation, the obtained LuVO4:Eu(3+) hollow spheres show strong red emissions
      located in the saturated color region, and the modulation of emission intensity
      and color purity could be realized by tuning the textural parameters of the
      obtained hollow spheres. It was found that the nanostructure of the building
      blocks of LuVO4:Eu(3+) hollow spheres also had an effect on the luminescent
      properties of the as-obtained materials. Moreover, the quantum efficiency could
      be affected by the textural parameters of the as-obtained LuVO4:Eu(3+) hollow
      spheres, and the double-shelled LuVO4:Eu(3+) hollow sphere has the highest
      quantum efficiency. In addition, the excellent biocompatibility indicates the
      potential biological applications of LuVO4 hollow spheres. 

PMID- 24308366
TI  - Alteration of choroidal thickness in a case of carotid cavernous fistula: a case
      report and a review of the literature.
AB  - BACKGROUND: To measure the alterations of the choroidal thickness in Carotid
      cavernous fistula (CCF) using enhanced depth imaging optical coherence tomography
      (EDI-OCT). CASE PRESENTATION: A 64-year-old woman was referred to us for redness,
      exophthalmos and visual disturbance in her right eye. She was diagnosed with CCF
      by magnetic resonance imaging (MRI) and magnetic resonance
      angiography.Observations; Embolization resulted in improvement of ocular
      symptoms, and there was a reduction of the subfoveal choroidal thickness in the
      right eye from 351 MUm preoperatively to 142 MUm postoperatively in EDI-OCT.
      CONCLUSION: EDI-OCT demonstrated that the choroidal thickness increases occurred
      due to congestion in a CCF case.

PMID- 24308368
TI  - Comparison and reappraisal of carbon electrodes for the voltammetric detection of
      dopamine.
AB  - The electro-oxidation of dopamine (DA) is investigated on the unmodified surfaces
      of five different classes of carbon electrodes: glassy carbon (GC), oxygen
      terminated polycrystalline boron-doped diamond (pBDD), edge plane pyrolytic
      graphite (EPPG), basal plane pyrolytic graphite (BPPG), and the basal surface of
      highly oriented pyrolytic graphite (HOPG), encompassing five distinct grades with
      step edge density and coverage varying by more than 2 orders of magnitude.
      Surfaces were prepared carefully and characterized by a range of techniques,
      including atomic force microscopy (AFM), field emission scanning electron
      microscopy (FE-SEM), and Raman spectroscopy. Although pBDD was found to be the
      least susceptible to surface fouling (even at relatively high DA concentrations),
      the reaction showed sluggish kinetics on this electrode. In contrast, DA electro
      oxidation at pristine basal plane HOPG at concentrations <=100 MUM in 0.15 M PBS,
      pH 7.2, showed fast kinetics and only minor susceptibility toward surface fouling
      from DA byproducts, although the extent of HOPG surface contamination by
      oxidation products increased substantially at higher concentrations (with the
      response similar on all grades, irrespective of step edge coverage). EPPG also
      showed a fast response, with little indication of passivation with repeated
      voltammetric cycling but a relatively high background signal due to the high
      capacitance of this graphite surface termination. Of all five carbon electrode
      types, freshly cleaved basal plane HOPG showed the clearest signal (distinct from
      the background) at low concentrations of DA (<10 MUM) as a consequence of the low
      capacitance. Studies of the electrochemical oxidation of DA in the presence of
      the common interferents ascorbic acid (AA) and serotonin (5-HT), of relevance to
      neurochemical analysis, showed that the signals for DA were still clearly and
      easily resolved at basal plane HOPG surfaces. In the presence of AA, repetitive
      voltammetry caused products of AA electro-oxidation to adsorb onto the HOPG
      surface, forming a permselective film that allowed the electrochemical oxidation
      of DA to proceed unimpeded, while greatly inhibiting the electrochemical response
      of AA itself. The studies presented provide conclusive evidence that the pristine
      surface of basal plane HOPG is highly active for the detection of DA,
      irrespective of the step edge density and method of cleavage, and adds to a
      growing body of evidence that the basal plane of HOPG is a much more active
      electrode for many classes of electrode reactions than previously believed. 

PMID- 24308369
TI  - Cervical spinal cord stimulation for the management of pain from brachial plexus
      avulsion.

PMID- 24308370
TI  - Effects of two weeks of metformin treatment on whole-body glycocalyx barrier
      properties in db/db mice.
AB  - BACKGROUND: The anti-diabetic drug metformin has been demonstrated to exert a
      protective effect against vascular complications in diabetes independent of its
      glucose lowering action. Since the endothelial glycocalyx has been indicated to
      have important vasculoprotective properties and to be vulnerable to degradation
      by hyperglycemic conditions, we evaluated in the current study the effect of
      short-term metformin treatment on whole-body glycocalyx barrier properties in a
      mouse model of non-insulin dependent diabetes mellitus (db/db mouse). METHODS:
      Glycocalyx barrier properties were measured in an acute experiment in three
      groups of mice: 1) db/db mice without treatment serving as controls, 2) db/db
      mice which received metformin for two weeks in the drinking water serving as
      experimental group, and 3) C57Bl/6 mice serving as reference group. Animals were
      put under anesthesia (ketamine, medetomidine, and atropine) and carotid artery
      blood pressure was continuously monitored. To probe the glycocalyx a mixture of
      the tracers FITC-labeled 70 kDa dextrans (Dex70) or fluorescein-labeled red blood
      cells (RBCs) versus Texas Red-labeled 40 kDa dextrans (Dex40) was infused and
      blood samples subsequently collected for 30 min to determine the initial vascular
      distribution volume and clearance of these tracers. Urine was collected and dry
      to-wet weight of heart and kidney were determined after the experiment. Group
      differences were tested using unpaired t-tests. RESULTS: Metformin treatment did
      not affect body weight, fasting blood glucose and arterial blood pressure.
      Compared to C57Bl/6 mice, db/db mice showed a diminished initial exclusion and
      increased vascular clearance of Dex70 versus Dex40 (P < 0.05), and both were
      improved by the metformin treatment (P < 0.05). While urine production was higher
      in the db/db mice compared to C57Bl/6 (P < 0.05), heart and kidney of the
      metformin treated animals showed comparable dry-to-wet weights compared to the
      C57Bl/6 mice. CONCLUSIONS: Two weeks of metformin in the drinking water is
      associated with an improvement in glycocalyx barrier properties in db/db mice, as
      evidence by an enhanced exclusion and retention of 70 kDa dextrans in the
      vasculature. In addition, metformin improved hydration of heart and kidney.
      Previous reported cardiovascular benefits of metformin may well involve an
      improvement of the endothelial glycocalyx.

PMID- 24308371
TI  - Coexistence of Cu, Fe, Pb, and Zn oxides and chlorides as a determinant of
      chlorinated aromatics generation in municipal solid waste incinerator fly ash.
AB  - We investigated chemical determinants of the generation of chlorinated aromatic
      compounds (aromatic-Cls), such as polychlorinated biphenyls (PCBs) and
      chlorobenzenes (CBzs), in fly ash from municipal solid waste incineration. The
      influences of the following on aromatic-Cls formation in model fly ash (MFA) were
      systematically examined quantitatively and statistically: (i) inorganic chlorides
      (KCl, NaCl, CaCl2), (ii) base materials (SiO2, Al2O3, CaCO3), (iii) metal oxides
      (CuO, Fe2O3, PbO, ZnO), (iv) metal chlorides (CuCl2, FeCl3, PbCl2, ZnCl2), and
      (v) "coexisting multi-models." On the basis of aromatic-Cls concentrations, the
      ?CBzs/?PCBs ratio, and the similarity between distribution patterns, MFAs were
      categorized into six groups. The results and analysis indicated that the
      formation of aromatic-Cls depended strongly on the "coexistence condition",
      namely multimodels composed of not only metal chlorides, but also of metal
      oxides. The precise replication of metal chloride to oxide ratios, such as the
      precise ratios of Cu-, Fe-, Pb-, and Zn-chlorides and oxides, may be an essential
      factor in changing the thermochemical formation patterns of aromatic-Cls.
      Although CuCl2 acted as a promoter of aromatic-Cls generation, statistical
      analyses implied that FeCl3 also largely influenced the generation of aromatic
      Cls under mixture conditions. Various additional components of fly ash were also
      comprehensively analyzed. 

PMID- 24308372
TI  - Bendamustine-rituximab: a cost-utility analysis in first-line treatment of
      indolent non-Hodgkin's lymphoma in England and Wales.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of bendamustine-rituximab (B-R)
      compared with CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone,
      rituximab) and CVP-R (cyclophosphamide, vincristine, prednisone, rituximab) as
      first-line treatment for patients with advanced indolent non-Hodgkin's lymphoma
      (NHL). METHODS: A patient-level simulation was adapted from the model used by the
      University of Sheffield School of Health and Related Research (ScHARR) in a
      health technology appraisal of rituximab for first-line treatment of follicular
      lymphoma. This approach allowed modelling of the complex treatment pathways in
      indolent NHL. Data from a Phase 3 randomized, open-label trial were used to
      compare B-R with CHOP-R. The relative efficacy of CHOP-R and CVP-R was estimated
      using an indirect treatment comparison similar to the original ScHARR approach.
      The analysis was conducted from the perspective of the National Health Service in
      England and Wales, using a lifetime time horizon. A number of one-way sensitivity
      and scenario analyses were conducted, including one using recently published data
      comparing CVP-R with CHOP-R. RESULTS: The deterministic incremental cost
      effectiveness ratio (ICER) was L5249 per quality adjusted life year (QALY) for B
      R vs CHOP-R, and L8092 per QALY for B-R vs CVP-R. The alternative scenario using
      direct data comparing CVP-R with CHOP-R approximately halved the ICER for B-R vs
      CVP-R to L4733. Owing to its better toxicity profile, B-R reduced the cost of
      treating adverse events by over L1000 per patient vs CHOP-R. LIMITATIONS: The
      main limitations were: immaturity of overall survival data from the Phase 3
      trial; reliance on quality-of-life data from previous health technology
      appraisals (as this was not collected in the trial); and a lack of direct
      evidence or a network of connected evidence comparing B-R with CVP-R.
      CONCLUSIONS: The ICERs for B-R vs CHOP-R and CVP-R were considerably below the
      thresholds normally regarded as cost-effective in England and Wales (L20,000
      30,000 per QALY).

PMID- 24308373
TI  - Excited state dynamics of photoswitchable fluorescent protein Padron.
AB  - The key events in the light-induced switching mechanism of the photochromic green
      fluorescent protein Padron have been investigated by employing femtosecond
      fluorescence up-conversion, femtosecond transient absorption, and time-correlated
      single photon counting techniques. In contrast to Dronpa, excitation of protein's
      neutral state at 395 nm triggers an efficient and complex photoswitching to a
      dark state whereas irradiation with 495 nm light reverses the protein to its
      initial state restoring the bright fluorescence. On the basis of the kinetics
      observed upon irradiation of the chromophore in the protonated state, we suggest
      that the switching mechanism consists of a light-initiated excited state process
      (presumably ESPT) with a time constant of 1 ps producing an unstable intermediate
      state, tentatively assigned to the excited state of the cis-anionic form, that is
      followed by a cis- to trans- isomerization (14.5 ps) forming the trans-anionic
      state in which the dark chromophore resides. In the trans-state, the protonation
      equilibrium strongly favors the anionic form. Consequently, upon excitation of
      the formed anionic species a trans-cis isomerization of the chromophore was found
      to occur with a time constant as fast as 5.2 ps switching the chromophore
      quantitatively to the bright (anionic) state. 

PMID- 24308374
TI  - Manipulating dietary PUFA in animal feed: implications for human health.
AB  - Milk, meat and eggs tend not to be regarded as an important source of PUFA. They
      are disproportionally high in SFA compared with their PUFA content, especially
      those from cattle and sheep, since their rumen microbes are responsible for the
      loss of over 90% of PUFA intake by livestock. This need not necessarily be the
      case since the relative proportion of PUFA in these foods is dictated by
      livestock management, especially feeding, and this can be manipulated to boost
      their content of crucial long-chain n-3 fatty acids and conjugated linoleic fatty
      acids. The present paper considers the fatty acid composition in animal-derived
      foods and how these can be manipulated to be more conducive for consumers'
      health. The importance of recognising the effect of livestock production systems
      on fat composition is also highlighted along with the fact that we may have to
      compromise between intensive, high levels of production and this particular
      aspect of food quality.

PMID- 24308376
TI  - Can stem-cell-derived models revolutionize drug discovery?
AB  - The pharmaceutical industry continues to struggle to bring new and innovative
      medicines to the market. Possible reasons for these challenges are the paradigms
      currently used during drug discovery and development. Over the last 15 years, our
      ability to study the pathology of human disease has increased tremendously. For
      example, the advent of human embryonic stem cells, and later the discovery of
      induced pluripotent stem cells, now make it possible to access large quantities
      of human specialized cells, address the issue of genetic diversity and to create
      disease models in a culture dish. Recently, the potential of pluripotent stem
      cell technologies in the pursuit of new medicines has been demonstrated through
      the in vitro recreation of many human diseases, and the subsequent use of these
      models in proof-of-concept drug screens. Ultimately, this can, together with the
      unlimited access to relevant human cells, aid in reducing both cost and attrition
      rate of new drug candidates. The field is now open for large-scale application of
      stem-cell-derived cells for both drug screening and safety assessment.

PMID- 24308375
TI  - Primary ciliary dyskinesia complicated with diffuse panbronchiolitis: a case
      report and literature review.
AB  - BACKGROUND: Fifty percent of patients with primary ciliary dyskinesia (PCD) have
      situs inversus. Diffuse panbronchiolitis (DPB) might be one of the characteristic
      features of the lung in PCD. METHODS: We reported a case of PCD without situs
      inversus, yet complicated with DPB, and did literature review. RESULTS: A 34-year
      old nonsmoking Chinese woman with 6-year primary infertility suffered from
      recurrent episodes of respiratory tract infections since childhood. Lung
      auscultation revealed end-inspiratory coarse crackles. Pulmonary function tests
      demonstrated mild obstructive ventilation functional impairment. Lung biopsy
      showed respiratory bronchiolitis. Nasal mucosa cilia showed the absence of both
      outer and inner dynein arms of the microtubules. Saccharin test was positive.
      Chest images showed bronchiectasis and bronchiolitis but no situs inversus.
      Paranasal sinus computed tomography (CT) showed maxillary sinusitis and ethmoid
      sinusitis. A culture of bronchoalveolar lavage fluid was positive for Pseudomonas
      aeruginosa. Her conditions improved in clinical symptoms and CT images after 2
      months of treatment with azithromycin. Literature review revealed that very rare
      patients were diagnosed as PCD complicated with diffuse DPB, and all of them had
      situs inversus. CONCLUSIONS: The association of DPB might be one of the
      characteristic features of the lung in PCD. Further studies on the concurrence of
      these two diseases are suggested so as to elucidate the mechanism of both.

PMID- 24308377
TI  - Emerging molecular methods for male infertility investigation.
AB  - Male factors account for approximately 50% of reproductive pathology. Different
      disorders, including urogenital and endocrine system development abnormalities,
      lead to testicular and gametogenesis defects. Parallely, studies have reported
      that somatic and germ cell genome decay are a major cause of male infertility. It
      has been shown that in somatic karyotype, there is a higher incidence of
      chromosomal aberrations in infertile men than neonatal population and significant
      chromosome Y microdeletion or specific gene alterations in affected
      spermatogenesis. Karyotyping and FISH application at somatic and germ cell levels
      are no longer sufficient to investigate the potential contribution of genome
      disorders on male infertility. A wide range of molecular methods are required for
      better understanding of male infertility causes. Molecular omes and omics
      techniques have become a great tool to investigate male infertility from
      chromosome to protein. This review reports different molecular tests and methods
      that can be offered for male infertility investigation. 

PMID- 24308378
TI  - Directed evolution of three-finger toxin to produce serine protease inhibitors.
AB  - Directed evolution is a very popular strategy for improving biophysical
      properties and even for generating proteins with novel functions. Recent advances
      in combinatorial protein engineering mean it is now possible to develop protein
      scaffolds that could substitute for whole antibody-associated properties as
      emerging therapeutic proteins. In particular, disulfide-rich proteins are
      attractive templates for directed evolution in the search for novel molecules
      because they can regulate the activities of receptors, enzymes, and other
      molecules. Previously, we demonstrated that functional regulatory molecules
      against interleukin-6 receptor (IL-6R) could be obtained by directed evolution of
      the three-finger toxin (3F) scaffold. In the present study, trypsin was selected
      as a target for directed evolution to further explore the potential use of the 3F
      cDNA display library. After seven rounds of selection, the DNA sequences
      converged. The recombinant proteins produced by the selected candidates had
      inhibitory activity against trypsin (Ki of 33-450 nM). Three of the six groups
      had Ki values that were comparable to bovine pancreatic trypsin inhibitor and
      soybean trypsin inhibitor. Two of the candidates also had inhibitory effects
      against chymotrypsin and kallikrein. This study suggests that 3F protein is
      suitable for the preparation of high-diversity libraries that can be utilized to
      obtain protease inhibitors. In addition to our previous successful targeting of
      IL-6R, the technique developed in our studies may have wide applications in the
      generation of regulatory molecules for targets of interest, such as receptors,
      enzymes for research, diagnostic applications, and therapeutic uses.

PMID- 24308379
TI  - Genetic architecture of resistance to Septoria tritici blotch in European wheat.
AB  - BACKGROUND: Septoria tritici blotch is an important leaf disease of European
      winter wheat. In our survey, we analyzed Septoria tritici blotch resistance in
      field trials with a large population of 1,055 elite hybrids and their 87 parental
      lines. Entries were fingerprinted with the 9 k SNP array. The accuracy of
      prediction of Septoria tritici blotch resistance achieved with different genome
      wide mapping approaches was evaluated based on robust cross validation scenarios.
      RESULTS: Septoria tritici blotch disease severities were normally distributed,
      with genotypic variation being significantly (P < 0.01) larger than zero. The
      cross validation study revealed an absence of large effect QTL for additive and
      dominance effects. Application of genomic selection approaches particularly
      designed to tackle complex agronomic traits allowed to double the accuracy of
      prediction of Septoria tritici blotch resistance compared to calculation methods
      suited to detect QTL with large effects. CONCLUSIONS: Our study revealed that
      Septoria tritici blotch resistance in European winter wheat is controlled by
      multiple loci with small effect size. This suggests that the currently achieved
      level of resistance in this collection is likely to be durable, as involvement of
      a high number of genes in a resistance trait reduces the risk of the resistance
      to be overcome by specific pathogen isolates or races.

PMID- 24308380
TI  - Effective extraction method for determination of neonicotinoid residues in tea.
AB  - Sample preparation using an absorbent for removal of polyphenols and a solid
      phase extraction (SPE) cartridge for cleanup followed by high-performance liquid
      chromatography (HPLC) has been investigated for the simultaneous determination of
      eight neonicotinoid insecticides (dinotefuran, nitenpyram, thiamethoxam,
      imidacloprid, clothianidin, imidaclothiz, acetamiprid, and thiacloprid). After
      tea samples were soaked with water and extracted with acetonitrile, sample
      extracts were treated with an appropriate amount of polyvinylpolypyrrolidone
      (PVPP) to effectively remove polyphenols. The treated extract was cleaned up with
      a Carb-PSA cartridge. Neonicotinoid insecticides were eluted with acetonitrile
      from the cartridge and dried. The extract was redissolved with methanol/water
      (1:9, v/v) and analyzed by conventional HPLC coupled with an ultraviolet
      detector. The recoveries of eight neonicotinoid insecticides in tea samples were
      71.4-106.6% at 0.1-1.0 mg kg(-1) spiked levels. Relative standard deviations were
      <10% for all of the recovery tests. The established method was simple, effective,
      and accurate and could be used for monitoring neonicotinoid insecticides in tea. 

PMID- 24308381
TI  - Duration of a cow-milk exclusion diet worsens parents' perception of quality of
      life in children with food allergies.
AB  - BACKGROUND: In Italy, rigorous studies obtained with specific and validated
      questionnaires that explore the impact of exclusion diets on health-related
      quality of life (HRQoL) in children with food allergies are lacking. In this
      cross-sectional study, we wished to validate the Italian version of a disease
      specific quality of life questionnaire, and assess the impact of exclusion diets
      on the HRQoL in a cohort of Italian children with IgE-mediated food allergies.
      METHODS: Children on an exclusion diet for >=1 food were enrolled consecutively,
      and their parents completed the validated Italian version of the Food Allergy
      Quality of Life Questionnaire-Parent Form (FAQLQ-PF) and Food Allergy Independent
      Measure (FAIM). RESULTS: Ninety-six parents of children aged 0-12 years answered
      the FAQLQ-PF. The validity of the construct of the questionnaire was assessed by
      correlation between the FAQLQ-PF and FAIM-PF (r = 0.85). The Italian version of
      the FAQLQ had good internal consistency (Cronbach's alpha >0.70). Factors that
      mainly influenced the HRQoL were older age, severity of food allergy, and the
      duration of the cow milk-exclusion diet. CONCLUSIONS: The FAQLQ-PF, validated in
      Italian, is a reliable instrument. Worse QoL scores were observed among older
      children, those with severe systemic reactions, and those with a prolonged cow
      milk-free diet. It is very important to consider the QoL assessment as an
      integral part of food-allergy management. These results emphasize the need to
      administer exclusion diets only for the necessary time and the importance of
      assessment of the HRQoL in these patients.

PMID- 24308382
TI  - Reorganization of cytoskeleton and transient activation of Ca2+ channels in
      mesenchymal stem cells cultured on silicon nanowire arrays.
AB  - Tissue engineering combines biological cells and synthetic materials containing
      chemical signaling molecules to form scaffolds for tissue regeneration.
      Mesenchymal stem cells (MSCs) provide an attractive source for tissue engineering
      due to their versatility of multipotent differentiation. Recently, it has been
      recognized that both chemical and mechanical stimulations are essential mediators
      of adhesion and differentiation of MSCs. While significant progress has been made
      on the understanding of chemical regulatory factors within the extracellular
      matrix, the effects of mechanical stimulation exerted by nanomaterials on MSCs
      and the underlying mechanisms are less well-known. The present study showed that
      the adhesion, proliferation, and differentiation of MSCs cultured on vertically
      aligned silicon nanowire (SiNW) arrays were significantly different from those on
      flat silicon wafer and control substrates. The interactions between MSCs and the
      SiNW arrays caused the stem cells to preferentially differentiate toward
      osteocytes and chondrocytes but not adipocytes in the absence of supplementary
      growth factors. Our study demonstrated that Ca(2+) ion channels were transiently
      activated in MSCs upon mechanical stimulation, which eventually led to activation
      of Ras/Raf/MEK/ERK signaling cascades to regulate adhesion, proliferation, and
      differentiation of MSCs. The stretch-mediated transient Ca(2+) ion channel
      activation and cytoskeleton reorganization during stem cell-nanowire interaction
      may be early events of lineage-specific potentiation of MSCs in determining the
      fates of mesenchymal stem cells cultured on microenvironments with specific
      mechanical properties. 

PMID- 24308383
TI  - A concise synthesis of (-)-lasonolide A.
AB  - Lasonolide A is a novel polyketide displaying potent anticancer activity across a
      broad range of cancer cell lines. Here, an enantioselective convergent total
      synthesis of the (-)-lasonolide A in 16 longest linear and 34 total steps is
      described. This approach significantly reduces the step count compared to other
      known syntheses. The synthetic strategy utilizes alkyne-bearing substrates as
      core building blocks and is highlighted by stitching together two similarly
      complex halves via a key Ru-catalyzed alkene-alkyne coupling and
      macrolactionization. 

PMID- 24308384
TI  - Electrophysiological evidence for early perceptual facilitation and efficient
      categorization of self-related stimuli during an Implicit Association Test
      measuring neuroticism.
AB  - The Implicit Association Test (IAT) is a widely used latency-based categorization
      task that indirectly measures the strength of automatic associations between
      target and attribute concepts. So far, little is known about the perceptual and
      cognitive processes underlying personality IATs. Thus, the present study examined
      event-related potential indices during the execution of an IAT measuring
      neuroticism (N  =  70). The IAT effect was strongly modulated by the P1 component
      indicating early facilitation of relevant visual input and by a P3b-like late
      positive component reflecting the efficacy of stimulus categorization. Both
      components covaried, and larger amplitudes led to faster responses. The results
      suggest a relationship between early perceptual and semantic processes operating
      at a more automatic, implicit level and later decision-related categorization of
      self-relevant stimuli contributing to the IAT effect.

PMID- 24308385
TI  - Crystal structure and cyclic hydrogenation property of Pr4MgNi19.
AB  - The hydrogen absorption-desorption property and the crystal structure of
      Pr4MgNi19 was investigated by pressure-composition isotherm measurement and X-ray
      diffraction (XRD). Pr4MgNi19 consisted of two phases: 52.9% Ce5Co19-type
      structure (3R) and 47.0% Gd2Co7-type structure (3R). Sm5Co19-type structure (2H)
      and Ce2Ni7-type structure (2H) were not observed in the XRD profile. The Mg atoms
      substituted at the Pr sites in a MgZn2-type cell. The maximum hydrogen capacity
      reached 1.14 H/M (1.6 mass%) at 2 MPa. The hysteresis factor, Hf = ln(Pabs/Pdes),
      was 1.50. The cyclic hydrogenation property of Pr4MgNi19 was investigated up to
      1000 absorption-desorption cycles. After 250, 500, 750, and 1000 cycles, the
      retention rates of hydrogen were reduced to 94%, 92%, 91%, and 90%, respectively.
      These properties were superior to those of Pr2MgNi9 and Pr3MgNi14. 

PMID- 24308386
TI  - Electronic communication in linear oligo(azobenzene) radical anions.
AB  - The radical anions of five bis(azobenzene) and one tris(azobenzene) compounds
      were studied by optical and electron paramagnetic resonance (EPR) spectroscopies
      in polar aprotic solvents. The radicals with planar or almost-planar bridges are
      charge-delocalized mixed-valence species. Localization of charge occurs only on
      radicals with highly twisted biphenyl bridges. The electronic coupling between
      the azobenzene charge-bearing units, calculated as half the energy of the
      intervalence band for the charge-delocalized and by the Hush equation for the
      charge-localized radicals, decreases with the distance and torsion angle between
      azobenzene units. These radicals have smaller electronic couplings between charge
      bearing units than other mixed-valence organic radicals with similar bridges.
      However, the application of a three-stage model to the tris(azobenzene) radical
      anion intervalence band yields an electronic coupling between consecutive
      azobenzenes that is higher than in any of the bis(azobenzene) radicals studied. 

PMID- 24308387
TI  - UV-irradiation-induced templated/in-situ formation of ultrafine silver/polymer
      hybrid nanoparticles as antibacterial.
AB  - Two types of facile approaches toward ultrafine Ag/polymer hybrid nanoparticles
      (NPs) within 10 nm are introduced. Template and in-situ formation method are
      developed by photoreduction based on inverse microemulsion (IME) polymerization
      of N,N-dimethylacrylamide (DMAA). The template method refers to the usage of size
      varied polymeric PDMAA NPs as templates for the preparation of Ag/PDMAA hybrids
      with desired morphology and optical property. To avoid the self-seeding
      nucleation of free Ag(+) in the solution, in-situ formation method is developed
      by introducing AgNO3 during IME polymerization, in which product hybrids could be
      obtained via autoprecipitation in large scale. Additionally, the produced
      Ag/PDMAA hybrids show high antibacterial performance. 

PMID- 24308388
TI  - Does experienced seclusion or restraint affect psychiatric patients' subjective
      quality of life at discharge?
AB  - BACKGROUND: In Finland major effort has been invested in reducing the use of
      coercion in psychiatric treatment, and the goal is to diminish the use of
      coercion by 40% by 2015. Improving patients' quality of life (QoL) has gained
      prominence in psychiatric treatment during the past decade. Numerous studies have
      shown that most secluded or restrained patients (S/R patients) would prefer not
      to have had this experience. Experience of S/R could affect negatively patients'
      QoL, but empirical data on this issue are lacking. AIM: The study aimed to
      explore the effect of experienced S/R on the subjective QoL of psychiatric in
      patients. METHOD: This study explored subjective QoL of the S/R patients. At
      discharge, S/R patients completed the Short Form of the Quality of Life Enjoyment
      and Satisfaction Questionnaire (Q-LES-Q-SF). RESULTS: We found that S/R patients'
      (n = 36) subjective QoL was significantly better than that of non-S/R patients'
      (n = 228). Most non-S/R patients were diagnosed with mood disorders (mostly
      depression). Most of S/R patients were diagnosed with schizophrenia, schizotypal
      and delusional disorders. The mean duration of S/R was 2.3 days, median was one
      day and mean length of the hospitalization after S/R episode was 2.5 months.
      CONCLUSION: Our cross-sectional findings suggest that S/R does not considerably
      influence patients' QoL or that the influence is short-lived. Because baseline
      QoL was not measured this remains uncertain. There are also many other factors,
      such as negative mood, which decrease the patients' QoL ratings. These factors
      may either mask the influence of S/R on QoL or modify the experience of QoL to
      such an extent that no independent association can be found at the time of
      discharge.

PMID- 24308389
TI  - Factors associated with poor asthma control among asthmatic patient visiting
      emergency department.
AB  - INTRODUCTION: Bronchial asthma is a common chronic disease that affects people of
      all ages. Insufficient asthma control may cause frequent emergency department
      (ED) visit by patients who seek crisis management of their asthma. OBJECTIVES:
      This study aims to identify the factors associated with poor asthma control.
      METHODS: We enrolled 450 participants who visited (ED) for asthma management.
      Besides assessing the asthma severity classification, we assess each participant
      for asthma control over the months preceding ED visit using Asthma Control Test
      score. We employed an independent t-test and ANOVA to assess if the differences
      in asthma control scores by demographic and clinical characteristics are
      statistically significant. The dependence of asthma control scores on demographic
      and clinical characteristics had been investigated with stepwise regression
      model. RESULTS: There are differences in asthma control scores by the number of
      ED visits and severity of asthma classification (P values = 0.001). It was found
      that participant age, multiple ED visits, severe persistent, moderate persistent,
      mild persistent, received education about asthma medication and received
      education about asthma disease were greatly affected asthma control scores. For
      instance, the asthma control is predicted to decrease by 10.688 when participant
      had severe persistent asthma. Similarly, the asthma control is predicted to
      decrease by 5.647 when the participant had moderate persistent asthma.
      CONCLUSIONS: This study identified many factors that may explain insufficient
      asthma control.

PMID- 24308390
TI  - Epidemiology and prevention of dental caries.

PMID- 24308391
TI  - Caries prevalence of children and adolescents in Bosnia and Herzegovina.
AB  - OBJECTIVE: The aim of this study was to present epidemiological parameters of
      caries prevalence in children and adolescents in index age groups on a national
      and regional level in Bosnia and Herzegovina (BH). MATERIALS AND METHODS: The
      study was conducted during 2004 year for children aged 6 and 12, and during 2007
      for adolescents aged 15. An oral health survey was performed on a total number of
      1,240 children and adolescents in line with World Health Organization methodology
      and criteria. Results for caries prevalence and treatment needs were presented
      and discussed in this paper. RESULTS: Mean dmft (decay, missing, filled teeth for
      primary dentition) for children aged six was 6.7 (SD+/-3.9) in that the decayed
      teeth constituted the major part of the index (88.8%), followed by extracted
      teeth (8.9%) and a small percentage of filled teeth (2.3%). In 12-year-olds DMFT
      (Decay, Missing, Filled Teeth for permanent dentition) was 4.2 (SD+/-2.9),
      Significant Caries index (SiC) was 7.7 (SD+/-2.9), the decayed teeth constituted
      the major part of the index (45.4%), followed by 42.1% of FT and 12.5% of
      extracted teeth. Among 15-year-olds the DMFT was 7.6 (SD+/-4.1), SiC was 9.2
      (SD+/-1.2), and filled teeth constituted the major part of the index. CONCLUSION:
      The present study provides some evidence of relatively high caries prevalence and
      severity in comparison with Western European countries. It is necessary to devote
      more attention to the oral health of children and adolescents. Community based
      oral health promotion, preventive programs and preventive oriented public dental
      health care services should be made available and accessible to all children in
      Bosnia and Herzegovina.

PMID- 24308392
TI  - Dental caries: strategies to control this preventable disease.
AB  - OBJECTIVE: To provide a brief commentary review of strategies to control dental
      caries. Dental decay is one of man's most prevalent diseases. In many counties,
      severity increased in parallel with importation of sugar, reaching its zenith
      about 1950s and 1960s. Since then, severity has declined in many countries, due
      to the wide use of fluoride especially in toothpaste, but dental caries remains a
      disease of medical, social and economic importance. Within the EU in 2011, the
      cost of dental treatment was estimated to be ?79 billion. The pathogenesis is
      well understood: bacteria in dental plaque (biofilm) metabolise dietary sugars to
      acids which then dissolve dental enamel and dentine. Possible approaches to
      control caries development, therefore, involve: removal of plaque, reducing the
      acidogenic potential of plaque, reduction in sugar consumption, increasing the
      tooth's resistance to acid attack, and coating the tooth surface to form a
      barrier between plaque and enamel. At the present time, only three approaches are
      of practical importance: sugar control, fluoride, and fissure sealing. The
      evidence that dietary sugars are the main cause of dental caries is extensive,
      and comes from six types of study. Without sugar, caries would be negligible.
      Fluoride acts in several ways to aid caries prevention. Ways of delivering
      fluoride can be classed as: 'automatic', 'home care' and 'professional care': the
      most important of these are discussed in detail in four articles in this issue of
      the Acta Medica Academica. CONCLUSION: Dental caries is preventable -
      individuals, communities and countries need strategies to achieve this.

PMID- 24308393
TI  - Water fluoridation and oral health.
AB  - Water fluoridation, is the controlled addition of fluoride to the water supply,
      with the aim of reducing the prevalence of dental caries. Current estimates
      suggest that approximately 370 million people in 27 countries consume fluoridated
      water, with an additional 50 million consuming water in which fluoride is
      naturally occurring. A pre-eruptive effect of fluoride exists in reducing caries
      levels in pit and fissure surfaces of permanent teeth and fluoride concentrated
      in plaque and saliva inhibits the demineralisation of sound enamel and enhances
      the remineralisation of demineralised enamel. A large number of studies conducted
      worldwide demonstrate the effectiveness of water fluoridation. Objections to
      water fluoridation have been raised since its inception and centre mainly on
      safety and autonomy. Systematic reviews of the safety and efficacy of water
      fluoridation attest to its safety and efficacy; dental fluorosis identified as
      the only adverse outcome. CONCLUSION: Water fluoridation is an effective safe
      means of preventing dental caries, reaching all populations, irrespective of the
      presence of other dental services. Regular monitoring of dental caries and
      fluorosis is essential particularly with the lifelong challenge which dental
      caries presents.

PMID- 24308394
TI  - Salt fluoridation and oral health.
AB  - The aim of this paper is to make known the potential of fluoridated salt in
      community oral health programs, particularly in South Eastern Europe. Since 1922,
      the addition of iodine to salt has been successful in Switzerland. Goiter is
      virtually extinct. By 1945, the caries-protective effect of fluorides was well
      established. Based on the success of water fluoridation, a gynecologist started
      adding of fluoride to salt. The sale of fluoridated salt began in 1956 in the
      Swiss Canton of Zurich, and several other cantons followed suit. Studies
      initiated in the early seventies showed that fluoride, when added to salt,
      inhibits dental caries. The addition of fluoride to salt for human consumption
      was officially authorized in 1980-82. In Switzerland 85% of domestic salt
      consumed is fluoridated and 67% in Germany. Salt fluoridation schemes are
      reaching more than one hundred million in Mexico, Colombia, Peru and Cuba. The
      cost of salt fluoridation is very low, within 0.02 and 0.05 ? per year and
      capita. Children and adults of the low socio-economic strata tend to have
      substantially more untreated caries than higher strata. Salt fluoridation is by
      far the cheapest method for improving oral health. CONCLUSION: Salt fluoridation
      has cariostatic potential like water fluoridation (caries reductions up to 50%).
      In Europe, meaningful percentages of users have been attained only in Germany
      (67%) and Switzerland (85%). In Latin America, there are more than 100 million
      users, and several countries have arrived at coverage of 90 to 99%. Salt
      fluoridation is by far the cheapest method of caries prevention, and billions of
      people throughout the world could benefit from this method.

PMID- 24308395
TI  - Milk fluoridation for the prevention of dental caries.
AB  - The aim of this review is to give an overview of 55 years experience of milk
      fluoridation and draw conclusions about the applicability of the method.
      Fluoridated milk was first investigated in the early 1950s, almost simultaneously
      in Switzerland, the USA and Japan. Stimulated by the favourable results obtained
      from these early studies, the establishment of The Borrow Dental Milk Foundation
      (subsequently The Borrow Foundation) in England gave an excellent opportunity for
      further research, both clinical and non-clinical, and a productive collaboration
      with the World Health Organization which began in the early 1980s. Numerous peer
      reviewed publications in international journals showed clearly the
      bioavailability of fluoride in various types of milk. Clinical trials were
      initiated in the 1980s - some of these can be classed as randomised controlled
      trials, while most of the clinical studies were community preventive programmes.
      CONCLUSION: These evaluations showed clearly that the optimal daily intake of
      fluoride in milk is effective in preventing dental caries. The amount of fluoride
      added to milk depends on background fluoride exposure and age of the children:
      commonly in the range 0.5 to 1.0 mg per day. An advantage of the method is that a
      precise amount of fluoride can be delivered under controlled conditions. The cost
      of milk fluoridation programmes is low, about ? 2 to 3 per child per year.
      Fluoridation of milk can be recommended as a caries preventive measure where the
      fluoride concentration in drinking water is suboptimal, caries experience in
      children is significant, and there is an existing school milk programme.

PMID- 24308396
TI  - Fluoride toothpastes and fluoride mouthrinses for home use.
AB  - OBJECTIVE: To provide a brief commentary review of fluoride-containing
      toothpastes and mouthrinses with emphasis on their use at home. Toothpastes and
      mouthrinses are just two of many ways of providing fluoride for the prevention of
      dental caries. The first investigations into incorporating fluoride into
      toothpastes and mouthrinses were reported in the middle 1940s. Unlike water
      fluoridation (which is 'automatic fluoridation'), fluoride-containing toothpastes
      and fluoridecontaining mouthrinses are, primarily, for home use and need to be
      purchased by the individual. By the 1960s, research indicated that fluoride could
      be successfully incorporated into toothpastes and clinical trials demonstrated
      their effectiveness. By the end of the 1970s, almost all toothpastes contained
      fluoride. The widespread use of fluoride- containing toothpastes is thought to be
      the main reason for much improved oral health in many countries. Of the many
      fluoride compounds investigated, sodium fluoride, with a compatible abrasive, is
      the most popular, although amine fluorides are used widely in Europe. The
      situation is similar for mouthrinses. Concentrations of fluoride (F), commonly
      found, are 1500 ppm (1500 MUg F/g) for toothpastes and 225 ppm (225 MUg F/ml) for
      mouthrinse. Several systematic reviews have concluded that fluoride-containing
      toothpastes and mouthrinses are effective, and that there is added benefit from
      their use with other fluoride delivery methods such as water fluoridation.
      Guidelines for the appropriate use of fluoride toothpastes and mouthrinses are
      available in many countries. CONCLUSION: Fluoride toothpastes and mouthrinses
      have been developed and extensive testing has demonstrated that they are
      effective and their use should be encouraged.

PMID- 24308397
TI  - The cariostatic mechanisms of fluoride.
AB  - This article discusses the possible cariostatic mechanisms of the action of
      fluoride. In the past, fluoride inhibition of caries was ascribed to reduced
      solubility of enamel due to incorporation of fluoride (F-) into the enamel
      minerals. The present evidence from clinical and laboratory studies suggests that
      the caries-preventive mode of action of fluoride is mainly topical. There is
      convincing evidence that fluoride has a major effect on demineralisation and
      remineralisation of dental hard tissue. The source of this fluoride could either
      be fluorapatite (formed due to the incorporation of fluoride into enamel) or
      calcium fluoride (CaF2)-like precipitates, which are formed on the enamel and in
      the plaque after application of topical fluoride. Calcium fluoride deposits are
      protected from rapid dissolution by a phosphate -protein coating of salivary
      origin. At lower pH, the coating is lost and an increased dissolution rate of
      calcium fluoride occurs. The CaF2, therefore, act as an efficient source of free
      fluoride ions during the cariogenic challenge. The current evidence indicates
      that fluoride has a direct and indirect effect on bacterial cells, although the
      in vivo implications of this are still not clear. CONCLUSION: A better
      understanding of the mechanisms of the action of fluoride is very important for
      caries prevention and control. The effectiveness of fluoride as a cariostatic
      agent depends on the availability of free fluoride in plaque during cariogenic
      challenge, i.e. during acid production. Thus, a constant supply of low levels of
      fluoride in biofilm/saliva/dental interference is considered the most beneficial
      in preventing dental caries.

PMID- 24308398
TI  - Experiences with amine fluoride containing products in the management of dental
      hard tissue lesions focusing on Hungarian studies: a review.
AB  - Fluorides play a significant role in the promotion of oral health, fostering
      remineralization, inhibiting demineralization processes in the enamel, and having
      antibacterial activity. The effects of fluorides are mostly exerted by their
      topical effect. The beneficial effect of amine fluorides (AmF) on caries and
      dental plaque reduction has been known for a long time. The caries reducing and
      plaque-inhibiting effect of stannous fluoride (SnF2) was also reported. However,
      the combination of amine fluoride/stannous fluoride has shown a much better
      inhibition of plaque accumulation then these products alone. There have been
      several clinical studies with AmF or AmF/ SnF2 products, using toothpaste, gel,
      combination of toothpaste and gel/fluid, toothpaste and mouth rinse. The aim of
      this article is to review the clinical experiences with these products based on
      Hungarian studies. The first Hungarian studies with AmF containing gel were
      published by Szoke and Kozma (1989) and Denes and Gabris (1991). Madlena et al.
      (2002) performed a study with an AmF-containing toothpaste and gel in high risk
      groups of adolescents. The first Hungarian study with AmF/SnF2 products was
      published by Banoczy et al. (1989). Based on the favourable results of these
      products used in combination for 12 weeks, other studies (Madlena et al. 2004,
      2012) assessed the effects of toothpastes and mouth rinse containing AmF/SnF2 on
      plaque accumulation, within a shorter period of time, in young adults and
      orthodontic patients. CONCLUSION: Regular use of different oral hygienic products
      containing an AmF and AmF/SnF2 combination contributes to the prevention of
      plaque accumulation and consequently to the prevention of dental diseases.

PMID- 24308399
TI  - Caries risk assessment models in caries prediction.
AB  - OBJECTIVE: The aim of this research was to assess the efficiency of different
      multifactor models in caries prediction. MATERIALS AND METHODS: Data from the
      questionnaire and objective examination of 109 examinees was entered into the
      Cariogram, Previser and Caries-Risk Assessment Tool (CAT) multifactor risk
      assessment models. Caries risk was assessed with the help of all three models for
      each patient, classifying them as low, medium or high-risk patients. The
      development of new caries lesions over a period of three years [Decay Missing
      Filled Tooth (DMFT) increment = difference between Decay Missing Filled Tooth
      Surface (DMFTS) index at baseline and follow up], provided for examination of the
      predictive capacity concerning different multifactor models. RESULTS: The data
      gathered showed that different multifactor risk assessment models give
      significantly different results (Friedman test: Chi square = 100.073, p=0.000).
      Cariogram is the model which identified the majority of examinees as medium risk
      patients (70%). The other two models were more radical in risk assessment, giving
      more unfavorable risk -profiles for patients. In only 12% of the patients did the
      three multifactor models assess the risk in the same way. Previser and CAT gave
      the same results in 63% of cases - the Wilcoxon test showed that there is no
      statistically significant difference in caries risk assessment between these two
      models (Z = -1.805, p=0.071). CONCLUSION: Evaluation of three different
      multifactor caries risk assessment models (Cariogram, PreViser and CAT) showed
      that only the Cariogram can successfully predict new caries development in 12
      year-old Bosnian children.

PMID- 24308400
TI  - Oral health attitudes and caries-preventive behaviour of Czech parents of
      preschool children.
AB  - OBJECTIVE: To characterize the oral health-related attitudes and behaviour of
      Czech parents of preschool children. MATERIALS AND METHODS: A representative
      sample of 796 parents was recruited for the cross-sectional questionnaire survey.
      Study data were collected using a validated questionnaire with 44 attitudinal
      items related to different aspects of caries prevention. The data were analyzed
      by explorative factor analysis, extracted factors were subjected to reliability
      analysis and Kruskal-Wallis ANOVA was used to test differences in the factor
      scores in respondents with different levels of education and self-perceived SES.
      RESULTS: The factor analysis extracted 3 factors, labelled "Toothbrushing -
      perceived significance and parental efficacy" ; "External caries control" and
      "Internal caries control". They explained 28.9% of the data variability. The
      comparison of the factor scores in groups with different SES and education of
      mothers showed highly significant differences. For all three factors, median
      values of the aggregated Likert scale increased with increasing SES and education
      of the mother. CONCLUSION: The parents report that they are aware of their
      responsibility for the prevention of tooth decay in their children. In caries
      prevention they concentrate on toothbrushing. Dietary measures do not seem to be
      of similar importance to them. The increasing self-perceived SES of the family
      and the education level of the mother have a significantly positive effect on the
      caries-preventive attitudes of the parents. Based on the study results, the
      message to the public health sector in the Czech Republic should include the need
      to highlight the importance of a non-cariogenic diet and the role of fluorides in
      caries prevention.

PMID- 24308401
TI  - Current possibilities in occlusal caries management.
AB  - Dental caries is a multifactorial disease that affects most populations
      throughout the world and it is still the primary cause of oral pain and tooth
      loss. The occlusal surfaces of posterior teeth are the most vulnerable sites for
      dental caries due to their anatomy. Therefore, the aim of the following article
      is to summarize current knowledge on occlusal caries development and the
      possibilities of its prevention. Although the overall caries rate today has
      fallen for populations in industrialized countries, the rate of occlusal surface
      caries has not decreased. This may be explained with fact that topically applied
      fluorides and their mode of action prevent caries better on smooth than on
      occlusal surfaces. As we know, tooth decay of first permanent molars causes a
      great deal of different short and long term difficulties for patients. Therefore,
      there is a continuous need for implementation of programs for caries prevention
      in permanent teeth. Nowadays, we like to treat our patients by minimally invasive
      methods. A very important step in our effective preventive treatment is sealing
      pits and fissures as a cornerstone of occlusal caries management. Reliable
      assessment of caries activity is also very important for defining treatment needs
      and plans. A very important decision, which should be made during occlusal caries
      management, is the selection of restorative material according to the treatment
      plan. CONCLUSION: Current possibilities in occlusal caries prevention and
      management are very effective. Therefore, dentists today do not have any excuse
      for avoiding the philosophy of Minimally Invasive Dentistry, especially when we
      talk about caries management of occlusal surfaces in permanent molars.

PMID- 24308402
TI  - The effect of different enamel surface treatments on microleakage of fissure
      sealants.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of different
      techniques of surface treatment on the microleakage of fissure sealants in
      permanent molar teeth in vitro. MATERIALS AND METHODS: 96 extracted impacted
      human third molars were randomly divided into 8 surface treatment groups
      (n=12/group) as 1. Er: YAG laser ; (Fidelis II, Fotona, Ljubljana, Slovenia) (125
      mj, 20Hz) ; 2. Er: YAG laser + 37% H3PO4 (15s) ; 3. ER: AG laser + 37%
      H3PO4+Prime&Bond NT ; 4. Er: YAG laser + G Bond ; 5. Er: YAG laser + Prime&Bond
      NT ; 6. 37% H3PO4 ; 7. 37% H3PO4 + Prime&Bond NT ; 8. G Bond. Sealant material
      (Clinpro, 3M ESPE, Seefeld, Germany), was applied into the fissures and light
      cured for 20s with LED (Bluephase C5, Ivoclar-Vivadent, Schaan, Liechtenstein).
      Specimens were subjected to thermocycling (1000*, 5-55 degrees C, dwell time:
      15s) and immersed in 0.5% basic fuchsin solution for 24h at 37 degrees C. The
      samples were sectioned and scored on a 3 point rating scale using a light
      microscope with a magnification of *20. One-way analysis of variance was used to
      analyze data. Multiple comparisons were analyzed using Bonferroni test (p=0.05).
      RESULTS: Er:YAG laser showed the highest microleakage scores whereas Er YAG laser
      + 37% H3PO4 showed the lowest. Although 37% H3PO4 group showed higher scores than
      Er:YAG laser + 37% H3PO4, the difference was not statistically significant.
      CONCLUSION: Etching fissures with phosphoric acid is sufficient prior to fissure
      sealant application.

PMID- 24308403
TI  - Demography and market impacts on dental practices' development in Bulgaria during
      the period of transition 1990-2010.
AB  - OBJECTIVE: The purpose of this study was to present the impact of demography and
      market dynamics on the organizational and technological development of dental
      practices in Bulgaria during the period of socio-economic transition from 1990 to
      2010. MATERIALS AND METHODS: Relevant data were gathered from the official
      registers of the Bulgarian Dental Association, National Health Insurance Fund,
      National Health Information Institute and research studies, published during the
      period 1990-2010. They were analysed and are discussed in this paper. RESULTS:
      During the period there was a decrease in population of Bulgaria, from 8,149,468
      in 2000 to 7,563,000 in 2010 and a movement from rural areas to cities. There was
      an aging population with an increase in oral health care needs at a time of
      decrease in the size of the national labour force and economic growth.
      Paradoxically, over the last 20 years, the number of dentists in Bulgaria
      increased by more than 50% from 1997 to 2008. The average age of dentists changed
      from 39.7 years in 1997 to 41.7 years in 2008. The number of group dental
      practices increased and the number of individual practices and group practices
      for specialized dental care and dental centres decreased. The utilization of
      dental services is currently "about half" that of the mean for all European Union
      Member States, which is over 80% per year. CONCLUSION: The growing number of
      elderly people who have retained their teeth suggests an increase in treatment
      needs. However, the decline in their purchasing power limits the demand for oral
      health care services. In order to meet this and other challenges Bulgarian
      dentists have started changing their traditional solo-practice to group-practice.

PMID- 24308404
TI  - Drug delivery systems for intra-articular treatment of osteoarthritis.
AB  - INTRODUCTION: Intra-articular (IA) drug delivery is very useful in the treatment
      of osteoarthritis (OA), the most common chronic joint affliction. However, the
      therapeutic effect of IA administration depends mostly on the efficacy of drug
      delivery. AREAS COVERED: The present article reviews the current status of IA
      therapy for OA treatment as well as its rationale. Outlines of drug delivery
      parameters such as release profile, retention time, distribution, size and
      transport that influence the drug's biological performance in the joints are
      summarized. New delivery systems, currently under investigation, including
      liposome, nanoparticle, microparticle and hydrogel formulations are introduced.
      Functionalized drug delivery systems by targeting and thermoresponsiveness that
      are being investigated for OA treatment via IA therapy are also addressed. EXPERT
      OPINION: Several delivery systems, including liposome, microparticles,
      nanoparticles and hydrogels, have been investigated for the sustained drug
      delivery to the joints. These can be advanced by the use of functionalized drug
      delivery systems that can lead targeting to specific regions and
      thermoresponsiveness for prolonged drug release in the joints. Further advances
      will bring forth new biocompatible and biodegradable materials as a drug carrier
      or new combination regimens. Future innovations in this field should be directed
      toward the development of adapted delivery systems that can induce tissue
      regeneration in OA patients.

PMID- 24308405
TI  - Quality of doctoral nursing education in the United Kingdom: exploring the views
      of doctoral students and staff based on a cross-sectional questionnaire survey.
AB  - AIM: To evaluate the quality of doctoral education in nursing in the United
      Kingdom. BACKGROUND: In recent decades, doctoral education programmes in nursing
      are increasing worldwide. There are many reasons for this and concerns have been
      raised regarding the quality of provision in and across countries. To date, the
      quality of doctoral education on a global level has not been reported in the
      literature. This United Kingdom study is part of a seven country investigation
      into the quality of doctoral education in nursing (Australia, Japan, Korea, South
      Africa, Thailand, United Kingdom and United States of America). DESIGN: A
      quantitative study using a cross-sectional comparative survey design. METHOD: An
      online survey was administered to collect the views of doctoral students and
      staff members on four domains: programme, faculty/staff, resource and evaluation.
      The study was carried out between 2010-2012. RESULTS: In most cases, staff
      perceived these more positively than students and the differences in perception
      were often statistically significant. Interestingly, many students rated the
      quality of supervision as excellent, whereas no staff member rated supervision
      this highly. The crucial importance of resources was confirmed in the path
      analysis of the four Quality of Doctoral Nursing Education domains. This
      demonstrates that investment in resources is much more cost-effective than
      investment in the other domains in relation to improving the overall quality of
      doctoral education in nursing. CONCLUSION: This study has wide-ranging
      implications for how the quality of doctoral education is monitored and enhanced.

PMID- 24308406
TI  - Lidocaine may be effective in alleviating physical symptoms in cancer patients.

PMID- 24308407
TI  - School burnout and cardiovascular functioning in young adult males: a hemodynamic
      perspective.
AB  - This study investigated aortic and brachial hemodynamic functioning that may link
      school burnout to cardiovascular risk factors. Methodological improvements from
      previous research were implemented including (1) statistical control of
      depressive and anxiety symptoms (2) resting, stress-induced and cardiac recovery
      condition comparisons and (3) use of pulse wave analysis. Forty undergraduate
      young adult males completed self-report measures of school burnout, trait anxiety
      and depressive symptoms. Participants then completed a protocol consisting of a
      10-min seated rest, 5-min baseline (BASE), 3-min cold pressor test (CPT) and a 3
      min recovery period (REC). Indices of brachial and aortic hemodynamics were
      obtained by means of pulse wave analysis via applanation tonometry. Controlling
      for anxiety and depressive symptoms, planned contrasts identified no differences
      in cardiovascular parameters at BASE between participants in burnout and non
      burnout groups. However, negative changes in hemodynamic indices occurred in
      burnout participants at CPT and REC as evidenced by increased aortic and brachial
      systolic and diastolic blood pressures, increased left ventricular work and
      increased myocardial oxygen consumption. Findings suggest that school burnout
      symptoms are associated with cardiac hyperactivity during conditions of cardiac
      stress and recovery and therefore may be associated with the early manifestations
      of cardiovascular disease. Future studies are suggested to reveal underlying
      autonomic mechanisms explaining hemodynamics functioning in individuals with
      school burnout symptomatology.

PMID- 24308408
TI  - Conventional and molecular diagnostic strategies for prosthetic joint infections.
AB  - An accurate diagnosis of prosthetic joint infection (PJI) is the mainstay for an
      optimized clinical management. This review analyzes different diagnostic
      strategies of PJI, with special emphasis on molecular diagnostic tools and their
      current and future applications. Until now, the culture of periprosthetic tissues
      has been considered the gold standard for the diagnosis of PJI. However,
      sonication of the implant increases the sensitivity of those cultures and is
      being increasingly adopted by many centers. Molecular diagnostic methods compared
      with intraoperative tissue culture, especially if combined with sonication, have
      a higher sensitivity, a faster turnaround time and are not influenced by previous
      antimicrobial therapy. However, they still lack a system for detection of
      antimicrobial susceptibility, which is crucial for an optimized and less toxic
      therapy of PJI. More studies are needed to assess the clinical value of these
      methods and their cost-effectiveness. 

PMID- 24308409
TI  - Exploring the use of mobile phone technology for the enhancement of the
      prevention of mother-to-child transmission of HIV program in Nyanza, Kenya: a
      qualitative study.
AB  - BACKGROUND: Community-based mobile phone programs can complement gaps in clinical
      services for prevention of mother-to-child transmission (PMTCT) of HIV in areas
      with poor infrastructure and personnel shortages. However, community and health
      worker perceptions on optimal mobile phone communication for PMTCT are
      underexplored. This study examined what specific content and forms of mobile
      communication are acceptable to support PMTCT. METHODS: Qualitative methods using
      focus groups and in-depth interviews were conducted in two district hospitals in
      Nyanza Province, Kenya. A total of 45 participants were purposefully selected,
      including HIV-positive women enrolled in PMTCT, their male partners, community
      health workers, and nurses. Semi-structured discussion guides were used to elicit
      participants' current mobile phone uses for PMTCT and their perceived benefits
      and challenges. We also examined participants' views on platform design and
      gender-tailored short message service (SMS) messages designed to improve PMTCT
      communication and male involvement. RESULTS: Most participants had access to a
      mobile phone and prior experience receiving and sending SMS, although phone
      sharing was common among couples. Mobile phones were used for several health
      related purposes, primarily as voice calls rather than texts. The perceived
      benefits of mobile phones for PMTCT included linking with health workers,
      protecting confidentiality, and receiving information and reminders. Men and
      women considered the gender-tailored SMS as a catalyst for improving PMTCT male
      involvement and couples' communication. However, informative messaging relayed
      safely to the intended recipient was critical. In addition, health workers
      emphasized the continual need for in-person counseling coupled with, rather than
      replaced by, mobile phone reinforcement. For all participants, integrated and
      neutral text messaging provided antenatally and postnatally was most preferred,
      although not all topics or text formats were equally acceptable. CONCLUSIONS:
      Given the ubiquity of mobile phones in Kenya and current health-related uses of
      mobile phones, a PMTCT mobile communications platform holds considerable
      potential. This pre-intervention assessment of community and health worker
      preferences yielded valuable information on the complexities of design and
      implementation. An effective PMTCT mobile platform engaging men and women will
      need to address contexts of non-disclosure, phone sharing, and linkages with
      existing community and facility-based services.

PMID- 24308410
TI  - Determinants of patient satisfaction with public hospital services.
AB  - The aim of this research is to propose and test a model of the causal
      relationships among the constructs of perceived service quality, consumption
      emotions, and satisfaction among users of public hospital services. The
      conceptual model proposed in this study postulates that: (a) perceived service
      quality is positively related to positive emotions and negatively related to
      negative emotions; (b) perceived service quality is positively related to patient
      satisfaction; and (c) positive emotions are positively related to patient
      satisfaction and negative emotions are negatively related to patient
      satisfaction. The model was tested with data from an empirical study in the
      Canadian public hospital setting. Data were collected from 314 respondents. The
      relationships between the constructs were tested using structural equation
      modeling by means of the EQS software. All hypothesized relationships were
      supported. The results confirm that perceived service quality exerts both direct
      and indirect effects (through positive and negative emotions) on satisfaction.
      The study demonstrates that emotions play an important role in determining
      satisfaction with hospital services. 

PMID- 24308411
TI  - Knowledge flows in health communities of practice.
AB  - This article will examine a case study of an outpatient's clinic in an Australian
      public hospital with the objective of gaining a better understanding of the
      issues related to knowledge dynamics in communities of practice within a health
      care environment. This case study research approach was considered to provide a
      fine-grained approach recommended for improved understanding of nuances, detail,
      and the forces underlying the phenomena under observation. Focus on detail was an
      important attribute of this study notwithstanding possible shortcomings in not
      being able to externalize the research findings. Of the four modes of knowledge
      exchange observed to take place in this public hospital community of practice,
      Mode C (tacit to explicit) stands out as a key finding. Here, the release of each
      individual's tacit knowledge is forthcoming and free flowing given the
      established culture of trust in this clinic. The informal communication
      environment in the luminal space of their workplace corridor provided a conducive
      environment that enabled a free-flowing exchange of community knowledge. Health
      care managers are increasingly required to guide the use and flow of knowledge
      within their organizations. The insights gained from this project will provide
      them with a better understanding of knowledge dynamics within a health-care
      community of practice, which is a microcosm of the larger organization. 

PMID- 24308412
TI  - Patient satisfaction scores and their relationship to hospital website quality
      measures.
AB  - Hospitals and health systems are using web-based and social media tools to market
      themselves to consumers with increasingly sophisticated strategies. These efforts
      are designed to shape the consumers' expectations, influence their purchase
      decisions, and build a positive reputation in the marketplace. Little is known
      about how these web-based marketing efforts are taking form and if they have any
      relationship to consumers' satisfaction with the services they receive. The
      purpose of this study is to assess if a relationship exists between the quality
      of hospitals' public websites and their aggregated patient satisfaction ratings.
      Based on analyses of 1,952 U.S. hospitals, our results show that website quality
      is significantly and positively related to patients' overall rating of the
      hospital and their intention to recommend the facility to others. The potential
      for web-based information sources to influence consumer behavior has important
      implications for policymakers, third-party payers, health care providers, and
      consumers. 

PMID- 24308413
TI  - Consumer choice of purchasing private-label drugs: an empirical study in China.
AB  - This research investigates factors influencing Chinese consumers' purchase choice
      of private-label drugs over rational brand equivalents. Survey data were
      collected from 251 Chinese consumers. Results show that their purchase choice of
      private-label drugs is significantly influenced by drug trust and perceptions of
      drug quality, but is not influenced by private-label drugs' price advantage.
      Store trust and perceived drug quality are significant predictors of drug trust.
      Store trust also positively affects perceived drug quality. Finally, store trust
      is significantly influenced by product quality and service quality. 

PMID- 24308414
TI  - Direct-to-consumer (DTC) antidepressant advertising and consumer misperceptions
      about the chemical imbalance theory of depression: the moderating role of
      skepticism.
AB  - Based on a survey with members of an online consumer panel (N= 699), this study
      revealed that: (a) a substantial percentage of consumers held misperceptions
      about the chemical imbalance theory of depression; (b) personal and interpersonal
      experiences with depression positively related to such misperceptions; (c)
      overall, exposure to direct-to-consumer (DTC) antidepressant advertising did not
      significantly relate to misperceptions; and (d) DTC exposure magnified
      misperceptions when consumers were highly trustful of DTC advertising, whereas
      exposure diluted misperceptions when consumers were highly skeptical. Theoretical
      and practical implications of the research are discussed, especially in light of
      the social responsibility of DTC advertising. 

PMID- 24308415
TI  - On reducing information asymmetry in U.S. health care.
AB  - Information asymmetry is a significant issue facing the U.S. health care system.
      In this article, we investigate some methods of reducing this asymmetry. We trace
      the information asymmetry using the "wicked problem" of the health care
      distribution system. An information asymmetry reduction method requiring joint
      responsibilities among health care stakeholders is developed. It is argued that
      information asymmetry is a contributor to enormous health care inflation. Hence,
      any reduction in such asymmetry will reduce health care costs. Concepts from both
      signaling and corrective justice theories are integrated in this article to help
      reduce the information asymmetry that exists in the U.S. health care system.
      Getting health care costs in line with other "advanced" nations, is the long-term
      solution to the wicked problem that currently exists in the U.S. health care
      system. There is an immediate need for a centralized health care database with
      adequate provisions for individual privacy. Both processes as well as an outcome
      based control system are essential for reducing information asymmetries in the
      U.S. health care system. 

PMID- 24308417
TI  - Does improved confidence in a disease relate to increased knowledge? Our
      experience with medical students.

PMID- 24308418
TI  - A literature review of the Dutch debate on the nurse practitioner role:
      efficiency vs. professional development.
AB  - AIM: To explore the debate on the development of the nurse practitioner
      profession in the Netherlands. BACKGROUND: In the Netherlands, the positives and
      negatives of nurse practitioners working in the medical domain have been debated
      since the role was introduced in 1997. The outcome of the debate is crucial for
      nurse practitioners' professional development and society's justification of
      their tasks. METHOD: Review of 14 policy documents, 35 opinion papers from
      nurses, 363 opinion articles from physicians and 24 Dutch research papers
      concerning nurse practitioners from 1995 to 2012. RESULTS: Two discourses were
      revealed: one related to efficiency and one to the development of the profession.
      In both, the nurse practitioner role was presented as a solution for healthcare
      and workforce problems, while arguments differed. The efficiency discourse seemed
      most influential. Opinions of nurse practitioners were underrepresented; taking
      up new responsibilities was driven by the wish to improve patient care. While
      most physicians were willing to delegate tasks to nurse practitioners, they
      wished to retain final responsibility for medical care. LIMITATIONS: All
      available publications were extensively studied, which could not include
      unpublished policy documents from the government or influential parties. This may
      have led to some selectivity. CONCLUSION: The case of the Netherlands shows that
      nurses in developing their advanced role are facing barriers, similar to those in
      other countries. The dominance of efficiency arguments combined with protection
      of medical autonomy undermines the development towards nursing care that really
      benefits patients. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse
      practitioners should strive to obtain positions in which they are allowed to make
      their own decisions and wise use of healthcare resources for the good of patients
      and society. Nurse practitioners should aim to become members of influential
      healthcare Boards in their countries, in which they can raise their voices and be
      involved in policy making.

PMID- 24308419
TI  - Lotus petal perforator flap for reconstruction of an extended chronic presacral
      defect after radiotherapy and rectal cancer resection.
AB  - AIM: As a result of their extent and complexity, pelvic wounds after surgery for
      anorectal malignancy often require a multidisciplinary approach to accomplish
      closure. This report describes a successful reconstruction using the lotus petal
      perforator flap. METHOD: This flap is based on perforators of the internal
      pudendal artery and was partially depithelialized for plugging the defect.
      RESULTS: Wound healing was achieved after 12 days. CONCLUSION: The lotus petal
      flap is a relatively simple and successful choice for reconstruction of an
      extended chronic presacral defect after radiotherapy and rectal cancer resection.

PMID- 24308420
TI  - A facile one-pot method to synthesize a polypyrrole/hemin nanocomposite and its
      application in biosensor, dye removal, and photothermal therapy.
AB  - In this work, we introduced a facile method for the construction of a
      polypyrrole/hemin (PPy/hemin) nanocomposite via one-pot chemical oxidative
      polymerization. In this process, a hemin molecule serving as a dopant was
      entrapped in the PPy nanocomposite during chemical oxidative polymerization.
      Scanning electron microscopy (SEM), transmission electron microscopy (TEM),
      Fourier transform infrared spectroscopy (FTIR), and UV-visible spectroscopy
      results demonstrated that the PPy/hemin nanocomposite was successfully
      synthesized. The as-prepared nanocomposite exhibited intrinsic peroxidase-like
      catalytic activities, strong adsorption properties, and an excellent near
      infrared (NIR) light-induced thermal effect. We utilized the nanomaterials to
      catalyze the oxidation of a peroxidase substrate 3,3,5,5-tetramethylbenzidine by
      H2O2 to the oxidized colored product which provided a colorimetric detection of
      glucose. As low as 50 MUM glucose could be detected with a linear range from 0.05
      to 8 mM. Moreover, the obtained nanocomposite also showed excellent removal
      efficiency for methyl orange and rhodamine B and a photothermal effect, which
      implied a promising application as the pollutant adsorbent and photothermal
      agent. The unique nature of the PPy/hemin nanocomposite makes it very promising
      for the fabrication of inexpensive, high-performance bioelectronic devices in the
      future. 

PMID- 24308422
TI  - Core-shell and asymmetric polystyrene-gold composite particles via one-step
      Pickering emulsion polymerization.
AB  - Core-shell structured polystyrene-gold composite particles are synthesized from
      one-step Pickering emulsion polymerization. The surface coverage of the core
      shell composite particles is improved with increasing gold nanoparticle (AuNP)
      hydrophobicity and concentration. At high surface coverage, the AuNPs exhibit an
      ordered hexagonal pattern, likely due to electrostatic repulsion during the
      emulsion polymerization process. In addition to core-shell structured polystyrene
      gold composite particles, an intriguing observation is that at low AuNP
      concentrations, asymmetric polystyrene-gold nanocomposite particles are
      simultaneously formed, where a single gold nanoparticle is attached onto each
      polystyrene particle. It is found that these asymmetric particles are formed via
      a "seeded-growth" mechanism. The core-shell and asymmetric polystyrene-gold
      composite particles prove to be efficient catalysts as they successfully catalyze
      the Rhodamine B reduction reaction with stable performance and show high
      recyclability as catalysts. 

PMID- 24308421
TI  - The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop)
      mononucleotide sequence variations, is associated with bladder cancer.
AB  - BACKGROUND: Bladder cancer is a relatively common and potentially life
      threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The
      aim of this study was to determine deletions and sequence variations in the
      mitochondrial displacement loop (D-loop) region from the blood specimens and
      tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral
      tissues. METHODS: The DNA from blood, tumoral tissues and adjacent non-tumoral
      tissues of twenty-six patients with bladder cancer and DNA from blood of 504
      healthy controls from different ethnicities were investigated to determine
      sequence variation in the mitochondrial D-loop region using multiplex polymerase
      chain reaction (PCR), DNA sequencing and southern blotting analysis. RESULTS:
      From a total of 110 variations, 48 were reported as new mutations. No deletions
      were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples
      from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not
      significantly correlated with bladder cancer, the C16069T variation was
      significantly present in patient samples compared to control samples (p < 0.05).
      Interestingly, there was no significant difference (p > 0.05) of C variations,
      including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between
      patients and control samples. CONCLUSION: Our study suggests that 16069
      mitochondrial DNA D-Loop mutations may play a significant role in the etiology of
      bladder cancer and facilitate the definition of carcinogenesis-related mutations
      in human cancer.

PMID- 24308423
TI  - Intramolecular phosphorus-phosphorus bond formation within a Co2P4 core.
AB  - The reduction of [(Cp'''Co)2(MU,eta(2:2)-P2)2] (Cp''' = 1,2,4-tBu3C5H2) with the
      samarocenes, [(C5Me4R)2Sm(THF)n] (R = Me or n-propyl), gives
      [(Cp'''Co)2P4Sm(C5Me4R)2]. This is the first example of an intramolecular P-P
      coupling in a polyphosphide complex upon reduction of the transition metal. The
      formation of the P-P bond is not a result of the direct reduction of the
      phosphorus atoms but is induced by a rearrangement of the positive charges
      between the metal atoms. 

PMID- 24308424
TI  - Identification of new developmentally regulated genes involved in Streptomyces
      coelicolor sporulation.
AB  - BACKGROUND: The sporulation of aerial hyphae of Streptomyces coelicolor is a
      complex developmental process. Only a limited number of the genes involved in
      this intriguing morphological differentiation programme are known, including some
      key regulatory genes. The aim of this study was to expand our knowledge of the
      gene repertoire involved in S. coelicolor sporulation. RESULTS: We report a DNA
      microarray-based investigation of developmentally controlled gene expression in
      S. coelicolor. By comparing global transcription patterns of the wild-type parent
      and two mutants lacking key regulators of aerial hyphal sporulation, we found a
      total of 114 genes that had significantly different expression in at least one of
      the two mutants compared to the wild-type during sporulation. A whiA mutant
      showed the largest effects on gene expression, while only a few genes were
      specifically affected by whiH mutation. Seven new sporulation loci were
      investigated in more detail with respect to expression patterns and mutant
      phenotypes. These included SCO7449-7451 that affect spore pigment biogenesis;
      SCO1773-1774 that encode an L-alanine dehydrogenase and a regulator-like protein
      and are required for maturation of spores; SCO3857 that encodes a protein highly
      similar to a nosiheptide resistance regulator and affects spore maturation; and
      four additional loci (SCO4421, SCO4157, SCO0934, SCO1195) that show developmental
      regulation but no overt mutant phenotype. Furthermore, we describe a new promoter
      probe vector that takes advantage of the red fluorescent protein mCherry as a
      reporter of cell type-specific promoter activity. CONCLUSION: Aerial hyphal
      sporulation in S. coelicolor is a technically challenging process for global
      transcriptomic investigations since it occurs only as a small fraction of the
      colony biomass and is not highly synchronized. Here we show that by comparing a
      wild-type to mutants lacking regulators that are specifically affecting processes
      in aerial hypha, it is possible to identify previously unknown genes with
      important roles in sporulation. The transcriptomic data reported here should also
      serve as a basis for identification of further developmentally important genes in
      future functional studies.

PMID- 24308425
TI  - Clinicopathological analysis and prognosis of extrahepatic bile duct cancer with
      a microscopic positive ductal margin.
AB  - BACKGROUND: The fate of a microscopic positive ductal margin (MPDM) of
      extrahepatic bile duct (EHBD) cancer is unclear. The purpose of this study was to
      analyse the clinicopathological features of EHBD cancer with MPDM and to identify
      the prognostic factors associated with survival. METHODS: Between 1995 and 2007,
      a retrospective analysis of 464 patients who had undergone surgical resection for
      EHBD cancer was conducted. Clinicopathological factors likely to influence
      survival were assessed using univariate and multivariate analysis. RESULTS: One
      hundred twenty-four patients had MPDM which included invasive carcinoma (IC) (n
      =85) and carcinoma in situ (CIS)/ high-grade dysplasia (HGD) (n = 39). The median
      survival (MS) of R0, R1 as CIS/ HGD, and R1 as IC were 41 months, 29 months, and
      18 months, respectively. Adverse prognostic factors were 'IC' on the resection
      margin [HR = 1.66, 95% confidence intervals (CIs) 1.06-2.59, P = 0.026], and no
      use of adjuvant chemoradiotherapy (HR = 1.57, 95% CIs 1.04-2.39, P = 0.033).
      Adjuvant chemoradiotherapy was beneficial in patients with MPDM as IC (5-year
      survival rate 19.7 compared with 2.8%, P = 0.011). CONCLUSIONS: The presence of
      MPDM is an important prognostic factor in EHBD cancer. When a ductal resection
      margin is positive, discrimination between 'IC' and 'CIS/ HGD' is important.

PMID- 24308426
TI  - Dimyristoyl phosphatidylcholine: a remarkable exception to alpha-tocopherol's
      membrane presence.
AB  - Using data obtained from different physical techniques (i.e., neutron
      diffraction, NMR and UV spectroscopy), we present evidence which explains some of
      the conflicting and inexplicable data found in the literature regarding alpha
      tocopherol's (aToc's) behavior in dimyristoyl phosphatidylcholine (di-14:0PC)
      bilayers. Without exception, the data point to aToc's active chromanol moiety
      residing deep in the hydrophobic core of di-14:0PC bilayers, a location that is
      in stark contrast to aToc's location in other PC bilayers. Our result is a clear
      example of the importance of lipid species diversity in biological membranes and
      importantly, it suggests that measurements of aToc's oxidation kinetics, and its
      associated byproducts observed in di-14:0PC bilayers, should be reexamined, this
      time taking into account its noncanonical location in this bilayer. 

PMID- 24308428
TI  - The importance of parental beliefs and support for pedometer-measured physical
      activity on school days and weekend days among Canadian children.
AB  - BACKGROUND: Parental influences are essential to the behaviours and physical
      activity of their children. Our study aimed to determine if parental beliefs and
      support are associated with children's pedometer measured physical activity
      levels on school days and weekend days. METHODS: In the spring of 2009 and 2011,
      we analyzed cross-sectional data from 1,355 grade five students and parents in 30
      schools in Alberta, Canada. Parents reported how much they care about exercising,
      how much they encourage their child to be physically active, and how frequently
      they engage in physical activities with their child. Physical activity was
      assessed from step counts obtained from time-stamped pedometers collected over
      nine consecutive days. RESULTS: Increased parental encouragement was positively
      associated with boys' and girls' physical activity on school days (Boys: beta =
      1373, 95% CI: 606, 2139; Girls: beta = 632, 95% CI: 108, 1155) and girls'
      physical activity on weekend days (beta = 997, 95% CI: 130, 1864). Increased
      parental care was positively associated with boys' physical activity on weekend
      days (beta = 1381, 95% CI: 85, 2676). Increased parental support and engagement
      was associated with an additional 632-1381 steps/day for children in this study.
      CONCLUSIONS: Parental care, encouragement and engagement are associated with
      physical activity levels of children 10-11 years of age. Policy makers and
      researchers should consider the importance of targeting parents when designing
      strategies to promote physical activity in children. This is particularly
      relevant to weekends and holidays when children's activity levels are low.

PMID- 24308429
TI  - Inhibition of the beta-catenin/Tcf signaling by caffeoylquinic acids in sweet
      potato leaf through down regulation of the Tcf-4 transcription.
AB  - Sweet potato leaves contain the highest levels of functional polyphenols. In this
      study the effects of the sweet potato leaf extract and its contents, such as mono
      (3, 4, and 5)-caffeoylquinic acid (CQA), di-CQA (4,5-diCQA, 3,5-diCQA, and 3,4
      diCQA) and caffeic acid (CA), were evaluated on the beta-catenin/Tcf-4 signaling
      in human colorectal cancer HCT116 cells. The extract and the CQA derivatives
      inhibited the beta-catenin/Tcf-4 signaling, and the inhibition of the di-CQA
      (with two caffeoyl groups) was higher than that of the mono-CQA (one-caffeoyl
      group) and CA, suggesting that the caffeoyl structure in the presence of a
      catechol group plays a significant role in interfering with the beta-catenin/Tcf
      4 signaling. In addition, the CQA derivatives had no effect on the beta-catenin
      protein expression, but all test compounds inhibited the expression of the Tcf-4
      transcription, and the inhibition of the di-CQA derivatives was stronger than
      those of the mono-CQA derivatives as well as the beta-catenin/Tcf-4
      transcriptional activity. These compounds can modulate the downstream Wnt
      signaling pathway, suggesting that sweet potato leaves can be a protective food
      for colorectal cancer. 

PMID- 24308430
TI  - Stable transformation and reverse genetic analysis of Penium margaritaceum: a
      platform for studies of charophyte green algae, the immediate ancestors of land
      plants.
AB  - The charophyte green algae (CGA, Streptophyta, Viridiplantae) occupy a key
      phylogenetic position as the immediate ancestors of land plants but,
      paradoxically, are less well-studied than the other major plant lineages. This is
      particularly true in the context of functional genomic studies, where the lack of
      an efficient protocol for their stable genetic transformation has been a major
      obstacle. Observations of extant CGA species suggest the existence of some of the
      evolutionary adaptations that had to occur for land colonization; however, to
      date, there has been no robust experimental platform to address this genetically.
      We present a protocol for high-throughput Agrobacterium tumefaciens-mediated
      transformation of Penium margaritaceum, a unicellular CGA species. The
      versatility of Penium as a model for studying various aspects of plant cell
      biology and development was illustrated through non-invasive visualization of
      protein localization and dynamics in living cells. In addition, the utility of
      RNA interference (RNAi) for reverse genetic studies was demonstrated by targeting
      genes associated with cell wall modification (pectin methylesterase) and
      biosynthesis (cellulose synthase). This provided evidence supporting current
      models of cell wall assembly and inter-polymer interactions that were based on
      studies of land plants, but in this case using direct observation in vivo. This
      new functional genomics platform has broad potential applications, including
      studies of plant organismal biology and the evolutionary innovations required for
      transition from aquatic to terrestrial habitats. 

PMID- 24308431
TI  - Application of SILAC labeling to primary bone marrow-derived dendritic cells
      reveals extensive GM-CSF-dependent arginine metabolism.
AB  - Although dendritic cells (DCs) control the priming of the adaptive immunity
      response, a comprehensive description of their behavior at the protein level is
      missing. The introduction of the quantitative proteomic technique of metabolic
      labeling (SILAC) into the field of DC research would therefore be highly
      beneficial. To achieve this, we applied SILAC labeling to primary bone marow
      derived DCs (BMDCs). These cells combine both biological relevance and
      experimental feasibility, as their in vitro generation permits the use of
      (13)C/(15)N-labeled amino acids. Interestingly, BMDCs appear to exhibit a very
      active arginine metabolism. Using standard cultivation conditions, ~20% of all
      protein-incorporated proline was a byproduct of heavy arginine degradation. In
      addition, the dissipation of (15)N from labeled arginine to the whole proteome
      was observed. The latter decreased the mass accuracy in MS and affected the
      natural isotopic distribution of peptides. SILAC-connected metabolic issues were
      shown to be enhanced by GM-CSF, which is used for the differentiation of DC
      progenitors. Modifications of the cultivation procedure suppressed the arginine
      related effects, yielding cells with a proteome labeling efficiency of >=90%.
      Importantly, BMDCs generated according to the new cultivation protocol preserved
      their resemblance to inflammatory DCs in vivo, as evidenced by their response to
      LPS treatment. 

PMID- 24308432
TI  - Detection of T-cell receptor gamma gene rearrangement in paraffin-embedded T or
      natural killer/T-cell lymphoma samples using the BIOMED-2 protocol.
AB  - While the use of polymerase chain reaction (PCR)-based clonality analysis of
      formalin-fixed paraffin-embedded (FFPE) tissue has recently become widespread,
      the detection sensitivity for lymphoma subtypes using FFPE samples is not well
      known. Here, we analyzed T-cell receptor gamma chain (TCRG) gene rearrangement
      clonality in 100 cases of T- or natural killer (NK)/T-cell lymphoma and examined
      detection sensitivity according to lymphoma subtype. Clonality was detected in
      approximately 80% of the major T-cell lymphoma subtypes: peripheral T-cell
      lymphoma, not otherwise specified, 84% (21/25 cases); angioimmunoblastic T-cell
      lymphoma, 71% (15/21 cases); and adult T-cell leukemia/lymphoma, 80% (8/10
      cases). The number of clonal peaks differed according to subtype. TCRG gene
      rearrangement was not detected in 63 cases of B-cell lymphoma or reactive
      lesions. Thus, clonality analysis can effectively and reliably detect TCRG gene
      rearrangement in T-cell lymphoma cases and could, therefore, be a useful
      diagnostic tool in routine practice.

PMID- 24308433
TI  - Bortezomib-based combination regimens in myeloma: more is not necessarily better.

PMID- 24308434
TI  - Bendamustine and melphalan kill myeloma cells similarly through reactive oxygen
      species production and activation of the p53 pathway and do not overcome
      resistance to each other.
AB  - Because the old alkylating drug bendamustine (BDM) is currently under evaluation
      in patients with multiple myeloma, we compared its efficacy to that of melphalan
      in 29 human myeloma cell lines (HMCLs). The concentrations of BDM and melphalan
      that killed 50% of cells (LD50) in HMCLs were linearly correlated (p < 0.001),
      and reactive oxygen (ROS) scavengers similarly inhibited cell death induced by
      both drugs. Sensitivity of HMCLs to both drugs was correlated to p53: the BDM and
      melphalan median LD50 values of TP53(wild-type) HMCLs were more than two-fold
      lower than those of TP53(abnormal) HMCLs (p < 0.001), and p53 silencing in
      TP53(wt) NCI-H929 cells inhibited BDM- and melphalan-induced cell death. Both
      drugs induced expression of p53 targets, p21, Puma and DR5, only in TP53(wt)
      HMCLs. In primary cells, both drugs induced an increase in DR5 expression in
      cells without del(17p). Finally, we demonstrated that the combined effect of BDM
      and melphalan was additive, and that BDM did not overcome melphalan resistance
      and vice versa.

PMID- 24308435
TI  - Dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide (SMILE)
      chemotherapy for relapsed or refractory adult lymphoblastic lymphoma.

PMID- 24308436
TI  - Spinal deformities and lung function in adults with osteogenesis imperfecta.
AB  - INTRODUCTION: There are no larger studies of adults with osteogenesis imperfecta
      (OI), focusing on the impact of spinal cord deformities on lung function
      assessment. OBJECTIVES: To assess prevalence and severity of spinal deformities
      and lung function in an adult population with OI and to explore whether
      compromise of lung function correlated with deformities of the spine. METHODS:
      Ninety-two adults with OI had radiographs of the spine, 75 underwent spirometry.
      Deformities were assessed radiographically using a semi-quantitative (SQ)
      approach grading each vertebra from mild to severe (0-3 SQ grades). The spinal
      deformity index (SDI) was calculated by summing the SQ grades of all vertebrae
      from TH4 to L4. Scoliosis was measured using the Cobb method. Pulmonary function
      tests were performed; both current measured and arm-span height were used for
      calculating the predicted lung volumes and flow rates. RESULTS: Vertebral
      deformities were found in 67%, the majority of deformities were found in the mid
      thoracic region. Scoliosis was found in 46%, nine patients exhibited torsion
      scoliosis. Median values of SDI were 2.0 in type I, 4.0 in type IV and 2.5 in the
      total population. Only correction with arm-span height had a significant impact
      on the assessment of lung function. Significant negative correlations were
      obtained when spirometry variables were correlated to spine deformities.
      CONCLUSIONS: OI patients show spinal deformities influencing body height and lung
      function. Lung function tests should be corrected for reductions in body height
      by using arm-span height. OI patients should be evaluated with spirometry when
      vertebral deformities are suspected.

PMID- 24308437
TI  - In vitro cytotoxicity, pharmacokinetics and tissue distribution in rats of MXN
      004, a novel conjugate of polyethylene glycol and SN38.
AB  - 1.  MXN-004 is a water-soluble PEGylated 7-ethyl-10-hydroxy-camptothecin (SN38).
      The aim of this study was to evaluate the in vitro cytotoxicity of MXN-004 and
      investigate pharmacokinetics and tissue distribution of MXN-004 and its active
      metabolite SN38 in rats. 2.  In vitro cytotoxicity of MXN-004 was tested in A549,
      HepG2 and Caco-2 cancer cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and compared with irinotecan. The
      pharmacokinetics and tissue distribution of MXN-004, irinotecan and their
      identical active metabolite SN38 were investigated after intravenous
      administration of MXN-004 and irinotecan at a same dose level of 16 MUmol/kg in
      rats. 3.  In vitro cytotoxicity study showed that MXN-004 was more potent in
      comparison with irinotecan. In rats, MXN-004 exhibited a longer half-life
      (sixfold) and much greater Vss as compared with irinotecan. The AUC0-infinity,
      T1/2 and Cmax of SN38 after intravenous administration of MXN-004 were higher
      than those of irinotecan (3.5-, 1.92- and 10.6-fold, respectively). In addition,
      the concentrations of SN38 released from MXN-004 were significantly higher in all
      tissues than those from irinotecan, especially in the lung. 4.  These results
      suggested that MXN-004 might be a more potential water-soluble antitumor agent
      with prolonged half-life of SN38 compared to irinotecan.

PMID- 24308438
TI  - Frequency and genotype distribution of ABCB1 gene polymorphisms among
      Maharashtrian population of Central India.
AB  - 1. Apart from conferring multidrug resistance to cancer cells, P-glycoprotein (P
      gp) encoded by the gene ABCB1 (also, known as Multidrug resistance gene, MDR1),
      plays a major role in drug disposition. Single nucleotide polymorphisms (SNPs) in
      the ABCB1 gene might contribute to inter-individual and ethnic differences in
      drug disposition and thereby, could influence the outcome and prognosis of
      certain diseases. 2. India is one of the most ethnically and genetically diverse
      regions of the world. This study was undertaken with a view to determine the
      allele and genotype frequencies of C3435T and C1236T polymorphisms in the ABCB1
      gene among the Maharashtrian population, residing in the Vidarbha region of
      central India and compare them with HapMap and other Indian populations. The
      common synonymous C3435T polymorphism has been found to be associated with lower
      P-gp functional expression and drug uptake, alone or in conjunction with a few
      other linked SNPs like C1236T. 3. The genotypes of C3435T and C1236T SNPs were
      determined by PCR-RFLP in 222 healthy and unrelated Maharashtrian individuals. 4.
      According to the findings of this study, the Maharashtrians were found to be not
      significantly different from the Gujarati Indians in Houston, Texas in the HapMap
      database.

PMID- 24308439
TI  - Clinical effectiveness of the obturator externus muscle injection in chronic
      pelvic pain patients.
AB  - BACKGROUND: Because of its anatomical location and function, the obturator
      externus (OE) muscle can be a source of pain; however, this muscle is
      understudied as a possible target for therapeutic intervention in pain practice.
      In this retrospective observational study, we evaluated the clinical
      effectiveness of the OE muscle injection with a local anesthetic in chronic
      pelvic pain patients with suspected OE muscle problems. METHODS: Twenty-three
      patients with localized tenderness on the inferolateral side of the pubic
      tubercle accompanied by pain in the groin, anteromedial thigh, or hip were
      studied. After identifying the OE with contrast dye under fluoroscopic guidance,
      5 to 8 mL of 0.3% lidocaine was injected. Pain scores were assessed before and
      after injection; patient satisfaction was also assessed. RESULTS: Mean pain score
      decreased by 44.7% (6.6 +/- 1.8 to 3.5 +/- 0.9, P < 0.001) 2 weeks after OE
      muscle injection as compared with pain score before injection. In addition, 82%
      of patients (19 of 23 patients) reported excellent or good satisfaction during 2
      weeks after injection. No patients reported complications from OE muscle
      injection. CONCLUSIONS: Fluoroscopy-guided injection of the OE muscle with local
      anesthetic reduced pain scores and led to a high level of satisfaction at short
      term follow-up in patients with suspected OE muscle problem. The results of this
      study suggest that OE muscle injection may be a valuable therapeutic option for a
      select group of chronic pelvic pain patients who present with localized
      tenderness in the OE muscle that is accompanied by groin, anteromedial thigh, or
      hip pain.

PMID- 24308440
TI  - Qualitative systematic review: the unique experiences of the nurse-family member
      when a loved one is admitted with a critical illness.
AB  - AIM: To interpret and synthesize nurse-family member experiences when a
      critically ill loved one is admitted to hospital. BACKGROUND: Having a family
      member hospitalized in a critical condition is an important stressor. When the
      family member is also a nurse, the provision of care is more complex, yet little
      research exists on this issue. DESIGN: Systematic review using Thomas and
      Harden's approach to thematic synthesis of qualitative research. DATA SOURCES:
      Primary studies were located by searching CINAHL, Proquest, Journals@Ovid,
      SCOPUS, Cochrane Library and Google Scholar. No date restrictions were applied
      due to a lack of relevant literature. All studies that met inclusion criteria
      were retrieved (n = 1717) and seven met the review aim. REVIEW METHODS: Following
      critical appraisal, seven studies from 1999-2011 describing the nurse-family
      member's experience were reviewed and synthesized. RESULTS: Six characteristics
      of the nurse-family member experience were identified: specialized knowledge;
      dual-role conflicts; competing expectations; building relationships; being 'let
      in'; and healthcare setting. CONCLUSION: Nurse-family members experience
      important stressors that can negatively affect their psychological health and
      experience as a healthcare consumer. Nurse-family members want a different type
      of care than other healthcare consumers. Acknowledging nurse-family members'
      specialized knowledge and dual role, keeping them fully informed and allowing
      them to be with the patient and feel in control can reduce their fear and
      anxiety. Further research is needed to develop a deeper understanding of the
      unique experiences, challenges and needs of nurse-family members to provide them
      with an enhanced level of care.

PMID- 24308441
TI  - Altered emotionality, hippocampus-dependent performance and expression of NMDA
      receptor subunit mRNAs in chronically stressed mice.
AB  - N-Methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission in the
      hippocampus is implicated in cognitive and emotional disturbances during stress
      related disorders. Here, using quantitative RT-PCR, we investigated the
      hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress
      paradigm that mimics clinically relevant conditions of simultaneously affected
      emotionality and hippocampus-dependent functions. A 2-week stress procedure,
      which comprised ethologically valid stressors, exposure to a rat and social
      defeat, was applied to male C57BL/6J mice. For predation stress, mice were
      introduced into transparent containers that were placed in a rat home cage during
      the night; social defeat was applied during the daytime using aggressive CD1
      mice. This treatment impaired hippocampus-dependent performance during contextual
      fear conditioning. A correlation between this behavior and food displacement
      performance was demonstrated, suggesting that burrowing behavior is affected by
      the stress procedure and is hippocampus-dependent. Stressed mice (n = 22) showed
      behavioral invigoration and anomalous anxiolytic-like profiles in the O-maze and
      brightly illuminated open field, unaltered short-term memory in the step-down
      avoidance task and enhanced aggressive traits, as compared to non-stressed mice
      (n = 10). Stressed mice showed increased basal serum corticosterone
      concentrations, hippocampal mRNA expression for the NR2A subunit of the NMDAR and
      in the NR2A/NR2B ratio; mRNA expression of NR2B and NR1 was unchanged. Thus,
      stress-induced aberrations in both hippocampal-dependent performance and
      emotional abnormalities are associated with alterations in hippocampal mRNA NR2A
      levels and the NR2A/NR2B ratio and not with mRNA expression of NR2B or NR1.

PMID- 24308442
TI  - Endolaparoscopic removal of colonic polyps.
AB  - AIM: A proportion of colonic polyps is not amenable to exclusively colonoscopic
      removal due to their location, size or tortuosity of the colon. A combined
      laparoscopic/colonoscopic polypectomy or endolaparoscopic polypectomy (ELP) is an
      alternative to formal segmental resection. We present our experience of ELP.
      METHOD: This is a retrospective review of a consecutive series of patients who
      underwent ELP for preoperatively diagnosed benign polyps between 2010 and 2013.
      Data are presented as median (interquartile range, IQR). RESULTS: Thirty patients
      commenced ELP. Eighteen were male and the median (IQR) age was 65.4 (61.6-73.5)
      years. Of 30 attempted cases, 22 (73%) underwent successful ELP surgery. Patients
      in whom combined ELP surgery was unsuccessful were converted to laparoscopic
      colectomy (one) or colonic mobilization and colotomy (seven). The median
      operation time for successful ELP was 105 (75-125) min. The complication rate was
      13.3% and the median length of stay was 2.0 (1.0-3.0) days for successful ELP
      compared with 5.5 (3.5-6.8) days for converted patients (P = 0.014). The median
      polyp size was 14 (10-22) mm; eight (26.7%) had high-grade dysplasia with two
      cases of invasive cancer identified. CONCLUSION: A combined endoscopic
      laparoscopic approach provides an alternative to segmental resection for treating
      challenging colonic polyps. This approach appears to be safe and effective and
      should be offered to selected patients with benign colonic polyps.

PMID- 24308443
TI  - Tailor-made charge-conversional nanocomposite for pH-responsive drug delivery and
      cell imaging.
AB  - Imaging labels, therapeutic drugs, as well as many other agents can all be
      integrated into one nanoplatform to allow for molecular imaging and therapy. With
      this in mind, herein we report the first example of a tailor-made charge
      conversional nanocomposite composed of mesoporous gamma-AlO(OH) and upconversion
      nanoparticles (UCNPs) via a simple and versatile method, and the obtained
      nanocomposite could be performed as a drug delivery carrier and applied for cell
      imaging. The nanocomposite (UCNPs-Al) was found to be able to efficiently
      transport DOX, a typical chemotherapeutic anticancer drug, into the cancer cell
      and release DOX from UCNPs-Al triggering by the mildly acidic environment. In
      vitro cell cytotoxicity assay verified that DOX-loaded nanocomposites (UCNPs-Al
      DOX) exhibited greater cytotoxicity with respect to free DOX at the same
      concentrations, because of the increase in cell uptake of anti-cancer drug
      delivery vehicles mediated by the charge-conversional property. Moreover, the UCL
      emission from UCNPs and the red fluorescence of DOX allow the nanocomposite to
      track and monitor the drug delivery system simultaneously. These findings have
      opened up new insights into designing and producing the highly versatile
      multifunctional nanoparticles for simultaneous imaging and therapeutic
      applications. 

PMID- 24308444
TI  - Comparing nursing handover and documentation: forming one set of patient
      information.
AB  - AIM: The aim of this study was to explore the potential for one set of patient
      information for nursing handover and documentation. BACKGROUND: Communication of
      patient information requires two processes in nursing: a verbal summary of the
      patients' care and another report within the nursing notes, creating duplication.
      INTRODUCTION: Advances in speech recognition technology have provided an
      opportunity to consider the practicality of one set of information at the nursing
      end-of-shift. METHODS: We used content analysis to compare transcripts from 162
      digitally recorded handovers and written nursing notes for similar patients
      within general medical-surgical wards from two metropolitan hospitals in Sydney
      Australia. FINDINGS: Using the Nursing Handover Minimum Dataset analysis
      framework similar content [n = 2109 (handover) n = 1902 (nursing notes)] was
      found within the handovers and notes at the end-of-shift (7:00 am and 2:00 pm).
      Analysis of the overarching categories demonstrated the emphasis within the
      differing data sources as: patient identification (31%), care planning or
      interventions (25%), clinical history (13%), and clinical status (13%) for
      handover, vs. care planning (47%), clinical status (24%), and outcomes or goals
      of care (12%) for nursing notes. DISCUSSION: This study has demonstrated that
      similar patient information is presented at handover and within documentation.
      Major categories are consistent with international nursing minimum datasets in
      use. CONCLUSION: We can use one set of patient information (within some
      limitations) for two purposes with system design, practice change and education.
      Experiments are currently being conducted trialling speech recognition within
      laboratory and clinical settings. IMPLICATIONS FOR NURSING AND HEALTH POLICY: One
      set of patient information, verbally generated at handover delivering electronic
      documentation within one process, will transform international nursing policy for
      nursing handover and documentation.

PMID- 24308445
TI  - A metapopulation model for highly pathogenic avian influenza: implications for
      compartmentalization as a control measure.
AB  - Although the compartmentalization of poultry industry components has substantial
      economic implications, and is therefore a concept with huge significance to
      poultry industries worldwide, the current requirements for compartment status are
      generic to all OIE member countries. We examined the consequences for potential
      outbreaks of highly pathogenic avian influenza in the British poultry industry
      using a metapopulation modelling framework. This framework was used to assess the
      effectiveness of compartmentalization relative to zoning control, utilizing
      empirical data to inform the structure of potential epidemiological contacts
      within the British poultry industry via network links and spatial proximity.
      Conditions were identified where, despite the efficient isolation of poultry
      compartments through the removal of network-mediated links, spatially mediated
      airborne spread enabled spillover of infection with nearby premises making
      compartmentalization a more 'risky' option than zoning control. However, when
      zoning control did not effectively inhibit long-distance network links,
      compartmentalization became a relatively more effective control measure than
      zoning. With better knowledge of likely distance ranges for airborne spread, our
      approach could help define an appropriate minimum inter-farm distance to provide
      more specific guidelines for compartmentalization in Great Britain.

PMID- 24308447
TI  - MALDI mass spectrometry imaging in microscope mode with infrared lasers:
      bypassing the diffraction limits.
AB  - This letter demonstrates the use of infrared matrix-assisted laser
      desorption/ionization coupled with microscope mode mass spectrometry imaging. It
      is aimed to explore the use of intrinsic water in tissue as a matrix for imaging
      at spatial resolutions below the diffraction limit of the employed IR optics.
      Stigmatic ion optics with a magnification factor of ~70 were used to project the
      spatial distribution of produced ions onto a detector while separating ions with
      different mass-to-charge ratios using a time-of-flight mass spectrometer. A
      pixelated detector was used to simultaneously record arrival time and impact
      position. A previously described dried-droplet sample system of 2,5
      dihydroxybenzoic acid (DHB) and 5 peptides covered by a copper grid for defined
      surface structure was used to benchmark the light- and ion-optical setup for
      spatial resolution and mass spectrometric performance. A spatial resolving power
      of 9.8 MUm, well below the optical limit of diffraction (14 MUm for the given
      setup), was established. After, frozen cryo-sections from a biological model
      system were measured by exploiting the endogenous water content as a matrix.
      Principal component analysis enabled a clear distinction between distinct tissue
      regions identified by both light microscopy and MS imaging.

PMID- 24308446
TI  - Mucosal immune responses predict clinical outcomes during influenza infection
      independently of age and viral load.
AB  - RATIONALE: Children are an at-risk population for developing complications
      following influenza infection, but immunologic correlates of disease severity are
      not understood. We hypothesized that innate cellular immune responses at the site
      of infection would correlate with disease outcome. OBJECTIVES: To test the
      immunologic basis of severe illness during natural influenza virus infection of
      children and adults at the site of infection. METHODS: An observational cohort
      study with longitudinal sampling of peripheral and mucosal sites in 84 naturally
      influenza-infected individuals, including infants. Cellular responses, viral
      loads, and cytokines were quantified from nasal lavages and blood, and correlated
      to clinical severity. MEASUREMENTS AND MAIN RESULTS: We show for the first time
      that although viral loads in children and adults were similar, innate responses
      in the airways were stronger in children and varied considerably between plasma
      and site of infection. Adjusting for age and viral load, an innate immune profile
      characterized by increased nasal lavage monocyte chemotactic protein-3, IFN
      alpha2, and plasma IL-10 levels at enrollment predicted progression to severe
      disease. Increased plasma IL-10, monocyte chemotactic protein-3, and IL-6 levels
      predicted hospitalization. This inflammatory cytokine production correlated
      significantly with monocyte localization from the blood to the site of infection,
      with conventional monocytes positively correlating with inflammation. Increased
      frequencies of CD14(lo) monocytes were in the airways of participants with lower
      inflammatory cytokine levels. CONCLUSIONS: An innate profile was identified that
      correlated with disease progression independent of viral dynamics and age. The
      airways and blood displayed dramatically different immune profiles emphasizing
      the importance of cellular migration and localized immune phenotypes.

PMID- 24308448
TI  - Sorbitol required for cell growth and ethanol production by Zymomonas mobilis
      under heat, ethanol, and osmotic stresses.
AB  - BACKGROUND: During ethanol fermentation, the ethanologenic bacterium, Zymomonas
      mobilis may encounter several environmental stresses such as heat, ethanol and
      osmotic stresses due to high sugar concentration. Although supplementation of the
      compatible solute sorbitol into culture medium enhances cell growth of Z. mobilis
      under osmotic stress, the protective function of this compound on cell growth and
      ethanol production by this organism under other stresses such as heat and ethanol
      has not been described yet. The formation of sorbitol in Z. mobilis was carried
      out by the action of the glucose-fructose oxidoreductase (GFOR) enzyme which is
      regulated by the gfo gene. Therefore, the gfo gene in Z. mobilis was disrupted by
      the fusion-PCR-based construction technique in the present study, and the
      protective function of sorbitol on cell growth, protein synthesis and ethanol
      production by Z. mobilis under heat, ethanol, and osmotic stresses was
      investigated. RESULTS: Based on the fusion-PCR-based construction technique, the
      gfo gene in Z. mobilis was disrupted. Disruption of the Z. mobilis gfo gene
      resulted in the reduction of cell growth and ethanol production not only under
      osmotic stress but also under heat and ethanol stresses. Under these stress
      conditions, the transcription level of pdc, adhA, and adhB genes involved in the
      pyruvate-to-ethanol (PE) pathway as well as the synthesis of proteins
      particularly in Z. mobilis disruptant strain were decreased compared to those of
      the parent. These findings suggest that sorbitol plays a crucial role not only on
      cell growth and ethanol production but also on the protection of cellular
      proteins from stress responses. CONCLUSION: We showed for the first time that
      supplementation of the compatible solute sorbitol not only promoted cell growth
      but also increased the ethanol fermentation capability of Z. mobilis under heat,
      ethanol, and osmotic stresses. Although the molecular mechanism involved in
      tolerance to stress conditions after sorbitol supplementation is still unclear,
      this research has provided useful information for the development of the
      effective ethanol fermentation process particularly under environmental
      conditions with high temperature or high ethanol and sugar concentration
      conditions.

PMID- 24308449
TI  - Catastrophic healthcare expenditure during economic recession in the field of
      cardiovascular disease.
AB  - Economic crisis drives many governments into drastic spending cuts in order to
      minimize their healthcare costs, resulting in an increase of out-of-pocket
      payment. This causes mainly the most vulnerable social groups, not only in poor
      countries, to lose their access to quality care and their ability to pay, and
      leads them in to catastrophic healthcare expenditures. Questions about whether
      health spending can be catastrophic rise across nations where there is an income
      reduction, unemployment and serious or chronic illness. Cardiovascular disease is
      the number one cause of death today. The first cost-of-illness study, which
      estimated the costs of cardiovascular disease in the EU in 2003, found them to be
      ?169 billion a year, while the most recent, in 2009, estimated them at nearly
      ?196 billion a year. Financial protection measures must be taken by governments
      in order to protect their citizens, particularly the most vulnerable ones. 

PMID- 24308450
TI  - Health-related quality of life in patients with acute coronary syndromes and
      treated with ticagrelor or clopidogrel.
AB  - Evaluation of: Levin LA, Wallentin L, Bernfort L et al. Health-related quality of
      life of ticagrelor versus clopidogrel in patients with acute coronary syndromes
      results from the PLATO trial. Value Health 16(4), 574-580 (2013). Antiplatelet
      therapy is considered essential treatment for acute coronary syndromes with or
      without ST-segment elevation and after stent procedures. The PLATelet inhibition
      and patient Outcomes (PLATO) trial compared ticagrelor or clopidogrel for the
      prevention of cardiovascular events. Prespecified substudies included a health
      related quality of life (HRQL) study; the EQ-5D, a self-report, standardized,
      nondisease-specific utility measure with a single index value for health status,
      was used to assess HRQL. In the primary HRQL analysis, the mean 12-month HRQL
      score in 15,212 patients was reported to be 0.840 in the ticagrelor group and
      0.832 in the clopidogrel group (p = 0.046). Excluding patients who died resulted
      in no difference in HRQL between patients treated with ticagrelor or clopidogrel
      (0.864 and 0.863, respectively; p = 0.69). The improved survival and reduction in
      cardiovascular events with ticagrelor as demonstrated in the main PLATelet
      inhibition and patient Outcomes trial are apparently obtained with no difference
      in quality of life. 

PMID- 24308451
TI  - Microbial volatile organic compound emissions from Stachybotrys chartarum growing
      on gypsum wallboard and ceiling tile.
AB  - BACKGROUND: Stachybotrys chartarum is a filamentous mold frequently identified
      among the mycobiota of water-damaged building materials. Growth of S. chartarum
      on suitable substrates and under favorable environmental conditions leads to the
      production of secondary metabolites such as mycotoxins and microbial volatile
      organic compounds (MVOCs). The aim of this study was to characterize MVOC
      emission profiles of seven toxigenic strains of S. chartarum, isolated from water
      damaged buildings, in order to identify unique MVOCs generated during growth on
      gypsum wallboard and ceiling tile coupons. Inoculated coupons were incubated and
      monitored for emissions and growth using a closed glass environmental growth
      chamber maintained at a constant room temperature. Gas samples were collected
      from the headspace for three to four weeks using Tenax TA tubes. RESULTS: Most of
      the MVOCs identified were alcohols, ketones, ethers and esters. The data showed
      that anisole (methoxybenzene) was emitted from all of the S. chartarum strains
      tested on both types of substrates. Maximum anisole concentration was detected
      after seven days of incubation. CONCLUSIONS: MVOCs are suitable markers for
      fungal identification because they easily diffuse through weak barriers like
      wallpaper, and could be used for early detection of mold growth in hidden
      cavities. This study identifies the production of anisole by seven toxigenic
      strains of Stachybotrys chartarum within a period of one week of growth on gypsum
      wallboard and ceiling tiles. These data could provide useful information for the
      future construction of a robust MVOC library for the early detection of this
      mold.

PMID- 24308452
TI  - The bark beetle, Ips grandicollis, disrupts biological control of the woodwasp,
      Sirex noctilio, via fungal symbiont interactions.
AB  - The corticoid fungus, Amylostereum areolatum, is deposited in pine trees by the
      woodwasp, Sirex noctilio, at the time of oviposition. This fungus is essential in
      S. noctilio larval growth and it is also a food source for Beddingia
      siricidicola, the nematode used for S. noctilio biological control. In recent
      years, the historically successful biological control programme has been
      disrupted in Australia by the bark beetle, Ips grandicollis. This study
      investigated whether the mechanism of this disruption involves a fungus,
      Ophiostoma ips, which I. grandicollis introduces into trees. In artificial and
      wood media, A. areolatum was unable to grow in areas occupied by O. ips. The
      latter fungus was faster growing, especially at 25  degrees C rather than 20 
      degrees C. Larval galleries of S. noctilio in field-collected samples were
      strongly associated with wood infested by A. areolatum and absent from areas
      affected by O. ips. The nematode failed to survive and reproduce on O. ips as it
      can on A. areolatum. Competitive interactions between O. ips and A. areolatum
      within the trap trees are demonstrated to be key factors in the negative effect
      of I. grandicollis on S. noctilio biological control programmes. 

PMID- 24308454
TI  - Small-bore catheter drainage of pleural injury after percutaneous
      nephrolithotomy: feasibility and outcome from a single large institution series.
AB  - BACKGROUND AND PURPOSE: A well-known complication of percutaneous nephrolithotomy
      (PCNL) is pleural injury. Pneumothorax and hydrothorax sustained during PCNL may
      necessitate the placement of a chest tube. Current literature describes placement
      of standard chest tubes as well as small-bore catheters for management of
      hydrothorax sustained during PCNL. This study aims to better delineate the
      clinical utility and outcomes associated with use of small-bore catheters when
      compared with standard chest tubes for managing pneumothorax and hydrothorax
      after PCNL. PATIENTS AND METHODS: We queried an institutional database of 735
      renal units that underwent PCNL for endourologic disease between 2001 and 2013.
      Postoperative upright chest radiographs were analyzed in patients who needed
      chest tube placement for pneumothorax or hydrothorax after PCNL. Those who met
      inclusion criteria were divided based on the size of chest tube placed: Small
      bore (8-12F) or standard chest tube (32F). Analysis of clinical outcomes was
      performed. RESULTS: Of the 735 procedures, 15 (2% of total, 7 right, 8 left)
      needed chest tube placement for a pleural injury after PCNL. Those who needed
      chest tube placement had an average stone size of 2.1 cm. Five had large-bore
      standard chest tubes (32F) and 10 had small-bore catheters (<14F) for management
      of pleural injury. The average length of time the chest tube stayed in place was
      3.9 days (minimum 2, maximum 6) for small bore and 4.4 days (minimum 2, maximum
      7) for standard chest tubes. There was a statistical trend toward decreased
      hospital stay and decreased length of time the chest tube was in place when a
      small-bore chest tube was used. CONCLUSION: The use of small-bore catheters for
      management of hydrothorax and pneumothorax have reasonable clinical outcomes when
      compared with standard large-bore chest tubes after PCNL.

PMID- 24308455
TI  - Computational examination of the mechanism of alkene epoxidation catalyzed by
      gallium(III) complexes with N-donor ligands.
AB  - The ability of gallium(III) complexes to catalyze the epoxidation of alkenes by
      peracetic acid has been examined with density functional theory calculations.
      According to the calculations, the chloride anions of the precatalyst
      [Ga(phen)2Cl2](+) (phen = 1,10-phenanthroline) can be displaced by either acetic
      or peracetic acid through dissociative ligand exchange pathways; both acetic and
      peracetic acid deprotonate upon binding to the formally tricationic metal center.
      Because of the high basicity of peracetate relative to that of chloride, only the
      acetate for chloride exchange occurs spontaneously, providing a rationale for the
      preponderance of gallium acetate adducts observed in the reaction mixtures. With
      respect to the mechanism of olefin epoxidation, the computational results suggest
      that the peracetic acid is most efficiently activated for redox activity when it
      binds to the metal center in a kappa(2) fashion, with the carbonyl oxygen atom
      serving as the second point of attachment. The phen ligands' coordination to the
      gallium is essential for the catalysis, and the lowest energy pathways for alkene
      oxidation proceed through hexacoordinate Ga(III) species with four Ga-N bonds. A
      natural bond order analysis confirms the electrophilic nature of the metal
      containing oxidant. 

PMID- 24308456
TI  - Growth and stabilization of silver nanoparticles on carbon dots and sensing
      application.
AB  - Carbon dots (C-dots) have been proven to show the capability for direct reduction
      of Ag(+) to elemental silver (Ag(0)) without additional reducing agent or
      external photoirradiation by incubating Ag(+) with C-dots for 5 min in a water
      bath at 50  degrees C. Silver nanoparticles (Ag-NPs) are simultaneously formed
      with an average size of 3.1 +/- 1.5 nm and grew on carbon dots. This process
      involves the oxidation of amine or phenol hydroxyl groups on the aromatic ring of
      C-dots. Meanwhile C-dots protect and stabilize the Ag-NPs from aggregation in
      aqueous medium; that is, the Ag-NPs are stable at least for 45 days in aqueous
      medium. The formed Ag-NPs cause significant resonance light scattering (RLS),
      which correlates closely with the concentration of silver cation, and this
      facilitates quantitative detection of silver in aqueous medium. 

PMID- 24308457
TI  - A cis-membrane FRET-based method for protein-specific imaging of cell-surface
      glycans.
AB  - Metabolic labeling of glycans with chemical reproters (e.g., alkyne or azide) in
      conjunction with bioorthogonal chemistry is a powerful tool for imaging glycome;
      however, this method lacks protein-specificity and therefore is not applicable to
      imaging glycosylation of a specific protein of interest (POI). Here we report the
      development of a cis-membrane FRET-based methodology that allows protein-specific
      imaging of glycans on live cells. We exploit metabolic glycan labeling in
      conjunction with site-specific protein labeling to simultaneously install a FRET
      acceptor and a donor onto the glycans and the extracellular terminal of the
      protein of interest, respectively. The intramolecular donor-acceptor distance for
      the POI falls within the range for effective FRET, whereas the intermolecular
      FRET is disfavored since the excess acceptors on other proteins are distant from
      the donor. We demonstrated the capability of this cis-membrane FRET imaging
      method by visualizing the sialylation of several important cell surface receptors
      including integrin alphaXbeta2, epidermal growth factor receptor, and
      transforming growth factor-beta receptor type I. Furthermore, our imaging
      experiments revealed that the sialylation might be important for beta2 integrin
      activation. Our methodology should enable the live-cell studies on how
      glycosylation regulates the functions and dynamics of various cell-surface
      proteins. 

PMID- 24308458
TI  - Early oral feeding after pancreatoduodenectomy enhances recovery without
      increasing morbidity.
AB  - OBJECTIVE: The aim of this study was to evaluate whether a change in the routine
      feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube
      (NJT) feeding to early oral feeding improved clinical outcomes. METHODS: An
      observational cohort study was performed in 102 consecutive patients undergoing
      PD. In period 1 (n = 51, historical controls), the routine postoperative feeding
      strategy was NJT feeding. This was changed to a protocol of early oral feeding
      with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort).
      The primary outcome was time to resumption of adequate oral intake. RESULTS: The
      baseline characteristics of study subjects in both periods were comparable. In
      period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53%
      (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or
      preoperative malnutrition (n = 7)]. The time to resumption of adequate oral
      intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P
      = 0.015), and the length of hospital stay shortened from 18 days in period 1 to
      13 days in period 2 (P = 0.015). Overall, there were no differences in the
      incidences of complications of Clavien-Dindo Grade III or higher, DGE, pancreatic
      fistula, postoperative haemorrhage and mortality between the two periods.
      CONCLUSIONS: The introduction of an early oral feeding strategy after PD reduced
      the time to resumption of adequate oral intake and length of hospital stay
      without negatively impacting postoperative morbidity.

PMID- 24308459
TI  - Lignin nanotubes as vehicles for gene delivery into human cells.
AB  - Lignin nanotubes (LNTs) synthesized from the aromatic plant cell wall polymer
      lignin in a sacrificial alumina membrane template have as useful features their
      flexibility, ease of functionalization due to the availability of many functional
      groups, label-free detection by autofluorescence, and customizable optical
      properties. In this report we show that the physicochemical properties of LNTs
      can be varied over a wide range to match requirements for specific applications
      by using lignin with different subunit composition, a function of plant species
      and genotype, and by choosing the lignin isolation method (thioglycolic acid,
      phosphoric acid, sulfuric acid (Klason), sodium hydroxide lignin), which
      influences the size and reactivity of the lignin fragments. Cytotoxicity studies
      with human HeLa cells showed that concentrations of up to 90 mg/mL are tolerated,
      which is a 10-fold higher concentration than observed for single- or multiwalled
      carbon nanotubes (CNTs). Confocal microscopy imaging revealed that all LNT
      formulations enter HeLa cells without auxiliary agents and that LNTs made from
      NaOH-lignin penetrate the cell nucleus. We further show that DNA can adsorb to
      LNTs. Consequently, exposure of HeLa cells to LNTs coated with DNA encoding the
      green fluorescent protein (GFP) leads to transfection and expression of GFP. The
      highest transfection efficiency was obtained with LNTs made from NaOH-lignin due
      to a combination of high DNA binding capacity and DNA delivery directly into the
      nucleus. These combined features of LNTs make LNTs attractive as smart delivery
      vehicles of DNA without the cytotoxicity associated with CNTs or the
      immunogenicity of viral vectors. 

PMID- 24308460
TI  - Aberrant gene expression in the Arabidopsis SULTR1;2 mutants suggests a possible
      regulatory role for this sulfate transporter in response to sulfur nutrient
      status.
AB  - Sulfur is required for the biosynthesis of cysteine, methionine and numerous
      other metabolites, and thus is critical for cellular metabolism and various
      growth and developmental processes. Plants are able to sense their physiological
      state with respect to sulfur availability, but the sensor remains to be
      identified. Here we report the isolation and characterization of two novel
      allelic mutants of Arabidopsis thaliana, sel1-15 and sel1-16, which show
      increased expression of a sulfur deficiency-activated gene beta-glucosidase 28
      (BGLU28). The mutants, which represent two different missense alleles of
      SULTR1;2, which encodes a high-affinity sulfate transporter, are defective in
      sulfate transport and as a result have a lower cellular sulfate level. However,
      when treated with a very high dose of sulfate, sel1-15 and sel1-16 accumulated
      similar amounts of internal sulfate and its metabolite glutathione (GSH) to wild
      type, but showed higher expression of BGLU28 and other sulfur deficiency
      activated genes than wild-type. Reduced sensitivity to inhibition of gene
      expression was also observed in the sel1 mutants when fed with the sulfate
      metabolites Cys and GSH. In addition, a SULTR1;2 knockout allele also exhibits
      reduced inhibition in response to sulfate, Cys and GSH, consistent with the
      phenotype of sel1-15 and sel1-16. Taken together, the genetic evidence suggests
      that, in addition to its known function as a high-affinity sulfate transporter,
      SULTR1;2 may have a regulatory role in response to sulfur nutrient status. The
      possibility that SULTR1;2 may function as a sensor of sulfur status or a
      component of a sulfur sensory mechanism is discussed. 

PMID- 24308462
TI  - End of year report.

PMID- 24308470
TI  - Small things make a difference.

PMID- 24308461
TI  - Direct probing of solvent accessibility and mobility at the binding interface of
      polymerase (Dpo4)-DNA complex.
AB  - Water plays essential structural and dynamical roles in protein-DNA recognition
      through contributing to enthalpic or entropic stabilization of binding complex
      and by mediating intermolecular interactions and fluctuations for biological
      function. These interfacial water molecules are confined by the binding partners
      in nanospace, but in many cases they are highly mobile and exchange with outside
      bulk solution. Here, we report our studies of the interfacial water dynamics in
      the binary and ternary complexes of a polymerase (Dpo4) with DNA and an incoming
      nucleotide using a site-specific tryptophan probe with femtosecond resolution. By
      systematic comparison of the interfacial water motions and local side chain
      fluctuations in the apo, binary, and ternary states of Dpo4, we observed that the
      DNA binding interface and active site are dynamically solvent accessible and the
      interfacial water dynamics are similar to the surface hydration water
      fluctuations on picosecond time scales. Our molecular dynamics simulations also
      show the binding interface full of water molecules and nonspecific weak
      interactions. Such a fluid binding interface facilitates the polymerase sliding
      on DNA for fast translocation whereas the spacious and mobile hydrated active
      site contributes to the low fidelity of the lesion-bypass Y-family DNA
      polymerase. 

PMID- 24308471
TI  - Care system must do more to protect girls from mutilation.

PMID- 24308479
TI  - Disappearing act.

PMID- 24308480
TI  - One size cannot fit all.

PMID- 24308481
TI  - How caring for a parent affects the psychosocial development of the young.
AB  - AIM: To investigate the impact of caring for a parent on the psychosocial
      development of the young person. METHODS: A total of 20 young carers and 20 non
      caregiving peers, aged 11-18 years, were compared on self-report measures of life
      satisfaction, self-esteem, and behavioural strengths and difficulties. Parental
      reports on their child's behaviour were obtained and measured. RESULTS: Young
      carers reported lower life satisfaction and self-esteem compared with non
      caregiving peers, and their parents rated them as having more difficulties with
      peer relationships and more emotional symptoms. There was no evidence of more pro
      social behaviour on the part of young carers. CONCLUSIONS: Caregiving has a
      negative effect on young people overall; improved support of and more research
      around young carers are required.

PMID- 24308482
TI  - Guidelines for routine gastrostomy tube replacement in children.
AB  - Endoscopic placement of a gastrostomy is the safest method of inserting a
      gastrostomy in children who are going to require full or supplemental enteral
      feeding for more than six weeks. Once a stoma tract has formed successfully
      following initial placement of a gastrostomy tube, the device can be changed to a
      balloon, button or non-balloon type. Community nursing teams often support a
      number of children with gastrostomies and their families, replacing the devices
      as necessary. Guidance for the safe insertion and replacement of balloon and
      button gastrostomies has been produced by the National Nurses Nutrition Group,
      the Patient Safety Agency and manufacturers, but standardised national guidelines
      are required. 

PMID- 24308483
TI  - Use of clowns to aid recovery in hospitalised children.
AB  - AIM: To examine how children in hospital perceive their meetings with clowns.
      METHODS: An interview study with ten children and an observation study of 12
      children were carried out at two different hospitals employing clowns in southern
      Sweden. FINDINGS: Analyses of the interviews produced four main thematic
      categories: the clowns' attributes, feelings that the clowns provoked, children's
      thoughts about the clowns' visit, and one negative experience. Analyses of the
      observations produced two main categories: clowns' interplay based on initiatives
      from children, and children's reactions to the event. The children experienced
      their hospital stay as being fun, which helped them feel more at home. A visit
      from the clowns was evidently important for the children. CONCLUSION: The clowns
      brought play and humour into the hospital and this gave children the opportunity
      to focus on something other than their illness, aiding their wellbeing and
      recovery.

PMID- 24308484
TI  - Managing children with raised intracranial pressure: part one (introduction and
      meningitis).
AB  - Intracranial pathologies in children need urgent identification and management.
      This article is presented in two parts, with part one describing intracranial
      pressure and outlining the features and management of meningitis. Part two, to be
      published in February 2014, outlines the features and management of brain tumours
      and intracranial bleeds. Each condition is accompanied by an illustrative case
      study to give an idea of what nurses might encounter in a child presenting with
      raised intracranial pressure. 

PMID- 24308485
TI  - Novel antimitotic activity of 2-hydroxy-4-methoxy-2',3'-benzochalcone (HymnPro)
      through the inhibition of tubulin polymerization.
AB  - The natural chalcones and their derivatives exhibit many biological activities,
      such as anti-inflammatory and antitumoral. However, the precise mechanisms of
      action of benzochalcone derivatives are currently unknown. Here, a set of
      benzochalcones was synthesized, and the molecular mechanisms underlying
      inhibition of tumor growth were investigated. Colony-forming assays revealed that
      among tested compounds, 2-hydroxy-4-methoxy-2',3'-benzochalcone (HymnPro) most
      effectively inhibited the clonogenicity of Capan-1 human pancreatic cancer cells.
      HymnPro inhibited cell proliferation in several human solid tumor cell lines and
      suppressed xenografted tumor growth in nude mice. Mechanistically, HymnPro
      induced cell cycle arrest at the G2/M phase, followed by an increase in apoptotic
      cell death. These events were associated with the inhibition of tubulin
      polymerization through binding of HymnPro to tubulin, leading to the formation of
      abnormal mono- or multipolar mitotic microtubule structures accompanied by
      spherical arrangement of multinucleated chromosomes. Furthermore, HymnPro
      activated caspase-2, caspase-9, caspase-3, and caspase-7 and increased the
      cleavage of poly(ADP-ribose) polymerase (PARP). HymnPro increased the
      phosphorylation of JNK1/2, Erk1/2, and p38 kinase. Pretreatment with SP600125,
      U0126, or SB600125 abrogated HymnPro-induced activation of caspases-3 and caspase
      7 and the cleavage of PARP, suggesting that MAPK signalings are involved in
      HymnPro-induced apoptosis. It was concluded that a novel HymnPro compound exerts
      antitumor activity by disrupting microtubule assembly, which leads to mitotic
      arrest and sequential activation of the caspase pathway, resulting in apoptosis. 

PMID- 24308486
TI  - Site-specific N-glycosylation analysis of human immunoglobulin e.
AB  - Immunoglobulin E (IgE) is a heterodimeric glycoprotein involved in antiparasitic
      and allergic immune reactions. IgE glycosylation is known to exhibit significant
      interindividual variation, and several reports have indicated its relevance in
      determining IgE activity. Here, we present site-specific glycosylation analysis
      of IgE from three different sources: IgE from the serum of a hyperimmune donor,
      from the pooled serum of multiple nondiseased donors, and from the pooled serum
      of 2 patients with IgE myeloma. The heavy chains were isolated and digested with
      either trypsin, proteinase K, or chymotrypsin, which permitted coverage of all
      seven potential N-glycosylation sites. The resulting (glyco-)peptides were
      analyzed by nano-reversed-phase-LC-MS/MS and MALDI-TOF/TOF-MS/MS. Site Asn264 was
      shown to be unoccupied. In all three samples, site Asn275 contained exclusively
      oligomannosidic structures with between 2 and 9 mannoses, whereas sites Asn21,
      Asn49, Asn99, Asn146, and Asn252 contained exclusively complex-type glycans. For
      the nonmyeloma IgE, the majority of these glycans were biantennary and core
      fucosylated and contained one or two terminal N-acetylneuraminic acids. In
      contrast, myeloma IgE showed a higher abundance of triantennary and
      tetraantennary glycan structures and a low abundance of species with a bisecting
      N-acetylglucosamine. Our approach allows comparison of the glycosylation of IgE
      samples in a site-specific manner. 

PMID- 24308487
TI  - Cardiovascular disease in relation to diabetes status in immigrants from the
      Middle East compared to native Swedes: a cross-sectional study.
AB  - BACKGROUND: Type 2 diabetes is highly prevalent in immigrants to Sweden from
      Iraq, but the prevalence of cardiovascular disease (CVD) and its risk factors are
      not known. In this survey we aimed to compare the prevalence of CVD and CVD
      associated risk factors between a population born in Iraq and individuals born in
      Sweden. METHODS: This population-based, cross-sectional study comprised 1,365
      Iraqi immigrants and 739 Swedes (age 30-75 years) residing in the same
      socioeconomic area in Malmo, Sweden. Blood tests were performed and socio
      demography and lifestyles were characterized. To investigate potential
      differences in CVD, odds ratios (ORs) with 95% confidence intervals (CIs) were
      estimated by multivariate logistic regression analysis with adjustment for
      metabolic, lifestyle and psychosocial risk factors for CVD. Outcome measures were
      odds of CVD. RESULTS: There were no differences in self-reported prevalence of
      CVD between Iraqi- and Swedish-born individuals (4.0 vs. 5.5%, OR 0.9, 95% CI 0.4
      1.8). However, the prevalence of type 2 diabetes was higher in Iraqi compared to
      Swedish participants (8.4 vs. 3.3%, OR = 4.2, 95% CI 2.6-6.7). Moreover, among
      individuals with type 2 diabetes, Iraqis had a higher prevalence of CVD (22.8 vs.
      8.0%, OR = 4.2, 95% CI 0.9-20.0), after adjustment for age and sex. By contrast,
      among those without diabetes, immigrants from Iraq had a lower prevalence of CVD
      than Swedes (2.2 vs. 5.5%, OR = 0.6, 95% CI 0.3-0.9).Type 2 diabetes was an
      independent risk factor for CVD in Iraqis only (OR = 6.8, 95% CI 2.8-16.2). This
      was confirmed by an interaction between country of birth and diabetes (p =
      0.010). In addition, in Iraqis, type 2 diabetes contributed to CVD risk to a
      higher extent than history of hypertension (standardized OR 1.5 vs. 1.4).
      CONCLUSIONS: This survey indicates that the odds of CVD in immigrants from Iraq
      are highly dependent on the presence or absence of type 2 diabetes and that type
      2 diabetes contributes with higher odds of CVD in Iraqi immigrants compared to
      native Swedes. Our study suggests that CVD prevention in immigrants from the
      Middle East would benefit from prevention of type 2 diabetes.

PMID- 24308488
TI  - Long-term outcome of robotic-assisted laparoscopic rectopexy for full-thickness
      rectal prolapse in elderly patients.
AB  - AIM: Full-thickness rectal prolapse is common in the elderly, but there are no
      particular practice guidelines for its surgical management. We evaluated
      retrospectively the perioperative and long-term clinical results and function in
      elderly and younger patients with complete rectal prolapse after robotic-assisted
      laparoscopic rectopexy (RALR). METHOD: Seventy-seven patients who underwent RALR
      between 2002 and 2010 were divided into Group A (age < 75 years, n = 59) and
      Group B (age > 75 years, n = 18). Operative time, intra- and postoperative
      complications, length of hospital stay, short-term and long-term outcomes,
      recurrence rate and degree of satisfaction were evaluated. RESULTS: There was no
      significant difference between the groups regarding operation time, conversion,
      morbidity or length of hospital stay. At a median follow-up of 51.8 (5-115)
      months, there was no difference in the improvement of faecal incontinence,
      recurrence and the degree of satisfaction. CONCLUSION: Robotic-assisted
      laparoscopic rectopexy is safe in patients aged over 75 years and gives similar
      results to those in patients aged < 75 years.

PMID- 24308489
TI  - An ASMT variant associated with bipolar disorder influences sleep and circadian
      rhythms: a pilot study.
AB  - Patients with bipolar disorder (BD) experience persistent circadian rhythm and
      sleep abnormalities during periods of remission, and biological studies have
      shown that these patients have abnormal melatonin secretion profiles or
      reactivity to light. We previously reported the association with BD of a common
      polymorphism (rs4446909) of the promoter of the acetylserotonin O
      methyltransferase (ASMT) gene, encoding one of the two enzymes involved in
      melatonin biosynthesis. This variant was associated with weaker transcription and
      lower levels of ASMT activity in lymphoblastoid cell lines. Actigraphy, based on
      the use of a mobile portable device for the analysis of sleep/wake cycles in
      natural conditions, may be useful for studies of carriers of the at-risk allele.
      We studied the association between the ASMT rs4446909 variant and sleep/activity,
      as assessed with the Pittsburgh Sleep Quality Index (PSQI) and by actigraphy, in
      53 subjects (25 patients with BD in remission and 28 healthy controls). The two
      groups were similar for age, sex ratio, current mood symptoms, body mass index
      and risk of sleep apnea syndrome. In the total sample, the GG at-risk genotype
      was associated with longer sleep duration (P = 0.03), greater activity in active
      periods of sleep (P = 0.015) and greater interday stability (P = 0.003). These
      associations remained significant when disease status was included in the model.
      Only the association with interday stability remained significant after
      correction for multiple testing. This pilot study thus shows that a BD-associated
      functional variant involved in the melatonin synthesis pathway influences sleep
      and circadian rhythms in bipolar patients in remission and controls. 

PMID- 24308490
TI  - Oxytocin differently regulates pressor responses to stress in WKY and SHR rats:
      the role of central oxytocin and V1a receptors.
AB  - The role of central oxytocin in the regulation of cardiovascular parameters under
      resting conditions and during acute stress was investigated in male normotensive
      Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In
      Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were
      recorded in WKY and SHR rats at rest and after an air-jet stressor during
      intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor
      (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR
      antagonist were determined in WKY rats after prior administration of a V1a
      vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by
      any of the ICV infusions either in WKY or in SHR rats. In control experiments
      (vehicle), the pressor response to stress was significantly higher in SHR.
      Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it
      in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor
      response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a
      significantly greater MABP response to stress than infusion of V1a antagonist and
      vehicle. This study reveals significant differences in the regulation of blood
      pressure in WKY and SHR rats during alarming stress. Specifically, the
      augmentation of the pressor response to stress by exogenous oxytocin in WKY rats
      is caused by its interaction with V1aR, and endogenous oxytocin regulates the
      magnitude of the pressor response to stress in WKY rats by simultaneous
      interaction with OTR and V1aR.

PMID- 24308491
TI  - A Perspective on Rational Designs of a Hemagglutinin Based Universal Influenza
      Vaccine.
AB  - BACKGROUND: The influenza virus is one of the most critical threats to public
      health with major economic impact. Though annual influenza vaccination is
      currently the most effective prevention strategy against flu epidemics and
      pandemics, the mutational evolution of the influenza virus tends to reduce the
      effectiveness of strain-specific vaccines. METHODS: For past decades, a broad
      spectrum of potentially universal influenza vaccines has been thoroughly
      investigated to suppress different strains and subtypes of influenza virus
      concomitantly. Universal influenza vaccines were attempted to be designed to
      target conserved regions of surface receptors to provide the necessary preventive
      strategy against new influenza outbreaks. CONCLUSIONS: Notably, the influenza
      hemagglutinin (HA) receptor has evolutionary conserved domains that can serve as
      basis for the rational design of a universal influenza vaccine. In this review,
      we examine recent studies on HA-based universal influenza vaccines and address
      their molecular mechanism.

PMID- 24308492
TI  - Kinetic properties and role of bacterial chitin deacetylase in the bioconversion
      of chitin to chitosan.
AB  - Chitin is an extremely insoluble material with very limited industrial use;
      however it can be deacetylated to soluble chitosan which has a wide range of
      applications. The enzymatic deacetylation of various chitin samples was
      investigated using the bacterial chitin deacetylase (CDA), which was partially
      purified from Alcaligenes sp. ATCC 55938 growth medium and the kinetic parameters
      of the enzyme were determined. Also, the efficiency of biocatalyst recycling by
      immobilization technique was examined. CDA activity reached its maximum (0.419
      U/ml) after 18 h of bacterial cultivation. When glycol chitin was used as a
      substrate, the optimum pH of the enzyme was estimated to be 6 after checking a pH
      range between 3 and 9, while the optimum temperature was found to be 35 degrees
      C. Addition of acetate (100 mM) in the assay mixture resulted in 50% loss of
      enzyme activity. The Km value of the enzyme is 1.6 * 10(-4) uM and Vmax is 24.7
      uM/min. The average activity of CDA was 0.38 U/ml for both of immobilized and
      freely suspended cells after 18 h of bacterial growth. Some related patents are
      also discussed here. 

PMID- 24308493
TI  - Nurses' job satisfaction and attitudes towards people living with HIV/AIDS in
      Russia.
AB  - BACKGROUND: Previous studies internationally have highlighted that working with
      people living with HIV/AIDS may lead to nurses' stress and burnout. However, this
      topic has not been well explored in Russia, a country with an exponential growth
      in HIV/AIDS. AIM: This study focused on nurses' job satisfaction and their
      attitudes towards people living with HIV/AIDS in centres where nurses regularly
      treat such patients, and in a general hospital where nurses rarely treat such
      patients. METHOD: We distributed three self-report questionnaires: demographics,
      job satisfaction and attitudes towards people living with HIV/AIDS to nurses
      working in six HIV/AIDS centres and the largest general hospital in Ekaterinburg,
      Russia. Sixty-nine nurses from the HIV/AIDS centres and 66 from the general
      hospital (about 90% of those approached) completed these. RESULTS: Nurses who
      regularly treated people with HIV/AIDS were significantly younger and a greater
      number held master degrees than those who rarely treated such patients. No
      significant differences between the two settings emerged for job satisfaction but
      what did emerge were differences in nurses' attitudes: nurses in HIV/AIDS centres
      reported less avoidance than nurses in the general hospital. Regarding empathetic
      attitudes, no significant differences emerged, but empathetic attitudes
      contributed to the explained variance of job satisfaction. CONCLUSION: Although
      our sample was small, the associations found between avoidant attitudes and job
      satisfaction highlight the need for stigma-reduction strategies and increased
      disease knowledge. Healthcare managers should consider attitudes towards people
      living with HIV/AIDS as an important factor in ensuring adequate care for them
      and initiate education programmes for nurses, especially programmes dealing with
      HIV/AIDS in general hospitals. IMPLICATIONS FOR NURSING AND HEALTH POLICY:
      Support and supervision can be used as a strategy, for empowering nurses to meet
      the challenges of working with HIV/AIDS patients.

PMID- 24308494
TI  - High-frequency stimulation of the subthalamic nucleus modifies the expression of
      vesicular glutamate transporters in basal ganglia in a rat model of Parkinson's
      disease.
AB  - BACKGROUND: It has been suggested that glutamatergic system hyperactivity may be
      related to the pathogenesis of Parkinson's disease (PD). Vesicular glutamate
      transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key
      anatomical and functional markers of glutamatergic excitatory transmission. Both
      VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic
      neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and
      VGLUT2 are thought to be expressed in a complementary manner in the cortex and
      the thalamus (VL/VM), in glutamatergic neurons involved in different
      physiological functions. Chronic high-frequency stimulation (HFS) of the
      subthalamic nucleus (STN) is the neurosurgical therapy of choice for the
      management of motor deficits in patients with advanced PD. STN-HFS is highly
      effective, but its mechanisms of action remain unclear. This study examines the
      effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in
      motor circuits, namely the basal ganglia (BG) network, in normal and 6
      hydroxydopamine (6-OHDA) lesioned rats. RESULTS: Here we report that: 1)
      Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but
      significantly decreased that of VGLUT2 in almost all BG structures studied; 2)
      STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal
      rats while, on the contrary, it systematically induced a significant increase of
      their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in
      VGLUT2 expression induced by the DA-depletion. CONCLUSIONS: These results show
      for the first time a comparative analysis of changes of expression for the three
      VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats.
      They provide evidence for the involvement of VGLUT2 in the modulation of BG
      cicuits and in particular that of thalamostriatal and thalamocortical pathways
      suggesting their key role in its therapeutic effects for alleviating PD motor
      symptoms.

PMID- 24308495
TI  - Persistent latent tuberculosis reactivation risk in United States immigrants.
AB  - RATIONALE: Current guidelines limit latent tuberculosis infection (LTBI)
      evaluation to persons in the United States less than or equal to 5 years based on
      the assumption that high TB rates among recent entrants are attributable to high
      LTBI reactivation risk, which declines over time. We hypothesized that high
      postarrival TB rates may instead be caused by imported active TB. OBJECTIVES:
      Estimate reactivation and imported TB in an immigrant cohort. METHODS: We linked
      preimmigration records from a cohort of California-bound Filipino immigrants
      during 2001-2010 with subsequent TB reports. TB was likely LTBI reactivation if
      the immigrant had no evidence of active TB at preimmigration examination, likely
      imported if preimmigration radiograph was abnormal and TB was reported less than
      or equal to 6 months after arrival, and likely reactivation of inactive TB if
      radiograph was abnormal but TB was reported more than 6 months after arrival.
      MEASUREMENTS AND MAIN RESULTS: Among 123,114 immigrants, 793 TB cases were
      reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6
      and 9% were reactivation of LTBI and inactive TB, respectively. Conversely,
      during Years 2-9 after U.S. entry, 76 and 24% were reactivation of LTBI and
      inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not
      decline during Years 1-9. CONCLUSIONS: High postarrival TB rates were caused by
      detection of imported TB through active postarrival surveillance. Among
      immigrants without active TB at baseline, reported TB did not decline over 9
      years, indicating sustained high risk of LTBI reactivation. Revised guidelines
      should support LTBI screening and treatment more than 5 years after U.S. arrival.

PMID- 24308497
TI  - A prospective study examining the association between preoperative frailty and
      postoperative complications in patients undergoing minimally invasive surgery.
AB  - BACKGROUND AND PURPOSE: Current surgical decision-making is overly subjective and
      often misjudges a patient's physiologic state. The concept of frailty has gained
      recent recognition and potentially represents a measureable phenotype, which can
      quantify a patient's physiologic reserve and risk of an adverse surgical outcome.
      We sought to investigate the relationship between preoperative markers of frailty
      and postoperative complications in patients undergoing minimally invasive surgery
      (MIS). METHODS: Frailty, using the methodology described by Fried and coworkers,
      was prospectively measured in patients who presented to urology, general surgery,
      and surgical oncology clinics where major MIS (endoscopic, laparoscopic, or
      robotic) was planned. The relationship between preoperative markers of frailty
      and 30-day postoperative complications was our primary outcome measure. RESULTS:
      Our cohort includes 80 patients. Mean age and body mass index were 60.0 (range 19
      87) years and 29.2 (range 18.4-53.1) kg/m(2), respectively. The majority of
      patients were male (57.5%) and Caucasian (65.0%). Thirteen patients were deemed
      "intermediately frail" or "frail," and the remaining 67 were classified as "not
      frail." Thirteen (16.25%) patients experienced any postoperative complication.
      Five (38.5%) of the intermediately frail and frail patients experienced a
      complication, compared with eight (11.9%) of the not frail patients (odds
      ratio=5.914; 95% confidence interval=1.25-27.96; P=0.025). CONCLUSION: The advent
      of MIS has potentially lured surgeons into thinking older and patients with
      comorbidities may more easily tolerate this surgical approach compared with
      traditional open techniques. Our data suggest, however, that intermediately frail
      or frail patients are at increased risk of experiencing postoperative
      complications compared with not frail patients.

PMID- 24308498
TI  - How half-coated janus particles enter cells.
AB  - Janus particles possess functional asymmetry and directionality within a single
      entity and thus are predicted to enable many promising biomedical applications
      that are not offered by homogeneous particles. However, it remains elusive what
      role the Janus principle plays in Janus particle-cell interactions, particularly
      in cellular uptake. We studied how asymmetric distribution of ligands on half
      coated Janus microparticles dictates the membrane dynamics during receptor
      mediated particle uptake, and found key differences from those characteristic of
      homogeneous particles. Live-cell fluorescence imaging combined with single
      particle level quantification of particle-cell membrane interactions shows that
      the asymmetric distribution of ligands leads to a three-step endocytic process:
      membrane cup formation on the ligand-coated hemisphere, stalling at the Janus
      interface, and rapid membrane protrusion on the ligand-absent hemisphere to
      complete the particle engulfment. The direct correlation between the spatial
      presentation of ligands on Janus particles and the temporal changes of membrane
      dynamics revealed in this work elucidates the potential of using the Janus
      principle to fine-tune particle-cell interactions. 

PMID- 24308499
TI  - Mechanisms of real-time, proximal sample processing during ambient ionization
      mass spectrometry.

PMID- 24308500
TI  - Initial treatment of transplant-ineligible patients in multiple myeloma.
AB  - Over two-thirds of newly diagnosed multiple myeloma are over 65 years. The
      treatment goals for the non-transplant-eligible patients should be to prolong
      survival by achieving the best response, while ensuring quality of life. New
      upfront treatment combinations based on first generation of novel proteasome
      inhibitors and immunomodulatory drugs plus alkylating agents, the historical
      platform, have significantly improved outcomes in the past 10 years. Other non
      alkylator induction regimens, essentially lenalidomide plus low-dose
      dexamethasone are also available and provide a novel backbone that may be
      combined with novel second- and third-generation drugs. Data indicate that
      prolonged treatment extends the progression-free survival. In summary, this group
      requires individualized and dose-modified regimens to improve tolerability and
      efficacy, while maintaining their quality of life. 

PMID- 24308501
TI  - Cell-membrane-permeable and cytocompatible phospholipid polymer nanoprobes
      conjugated with molecular beacons.
AB  - To enable the visualization of the distribution and dynamics of intracellular
      biomolecules and thereby understand the mechanisms of intracellular bioreactions,
      we developed a specific functional nanoprobe through the combination of a well
      designed, cytocompatible phospholipid polymer and molecular beacons (MBs). A
      water-soluble, amphiphilic phospholipid polymer, poly[2-methacryloyloxyethyl
      phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-N
      succinimidyloxycarbonyl tetra(ethylene glycol) methacrylate] (PMBS), was
      synthesized and conjugated with MBs to form nanoprobes via a chemical reaction
      between the ester group of N-hydroxysuccinimide and the amine group of the MBs.
      Surface tension measurements indicated that the polymeric nanoprobes had
      different conformations in aqueous solution, specifically at a concentration of
      1.0 mg/mL. The PMBS, containing the large, hydrophobic BMA, formed polymer
      aggregates. The carcinoma cells used to test the probes remained 100% viable
      after incubation with PMBS-MB probes. The polymeric nanoprobes demonstrated not
      only a high target specificity but also resistance to nonspecific adsorption of
      proteins compared with unconjugated MBs and were able to penetrate the cytoplasm
      of the cells, allowing the live imaging of mRNA. In summary, MPC polymer-MB
      nanoprobes have great potential for practical application for the noninvasive
      monitoring of intracellular biomolecules and bioreactions in real time. 

PMID- 24308502
TI  - Second outbreak of infection with a rare Cryptosporidium parvum genotype in
      schoolchildren associated with contact with lambs/goat kids at a holiday farm in
      Norway.
AB  - In March 2012, a second outbreak of Cryptosporidium parvum affected children
      following a stay at a holiday farm in Norway; the first outbreak occurred in
      2009. We studied a cohort of 145 schoolchildren who had visited the farm, of
      which 40 (28%) were cases. Cryptosporidium oocysts were detected in faecal
      samples from humans, goat kids and lambs. Molecular studies revealed C. parvum
      subtype IIa A19G1R1 in all samples including human samples from the 2009
      outbreak. A dose-response relationship was found between the number of optional
      sessions with animals and illness, increasing from two sessions [risk ratio (RR)
      2.7, 95% confidence interval (CI) 0.6-11.5] to six sessions (RR 8.0, 95% CI 1.7
      37.7). The occurrence of two outbreaks 3 years apart, with the same subtype of C.
      parvum, suggests that the parasite is established in the farm's environment. We
      recommend greater emphasis on hand hygiene and routines related to animal
      contact.

PMID- 24308503
TI  - Demonstration of staphylococci with inducible macrolide-lincosamide-streptogramin
      B (MLSB ) resistance in sewage and river water and of the capacity of
      anhydroerythromycin to induce MLSB.
AB  - Staphylococci causing diseases in humans and animals are well described, whereas
      not very much is known about the staphylococci in natural ecosystems. Due to
      increased consumption of antibiotics, multiresistant species are released with
      excrements. Therefore, 1048 staphylococci from raw and treated sewage and from
      receiving water bodies were isolated, identified and tested for resistance
      against erythromycin, clindamycin, oxacillin and ciprofloxacin. More resistant
      staphylococci were present in raw sewage (33.8%) than in treated sewage (24.9%)
      or river water (10.9%). Of all isolates, 20.2% were resistant against the
      macrolide erythromycin which can induce cross-resistance against lincosamides and
      streptogramin B antibiotics (iMLSB ). Erythromycin is metabolized to
      anhydroerythromycin and excreted with urine into sewage. The question arises
      whether anhydroerythromycin can also induce resistance against MLSB antibiotics
      in staphylococci. This was investigated with antibiotic susceptibility tests (D
      tests) and macrodilution assays. Staphylococci with iMLSB phenotype in river
      water were more numerous (27.8%) than in treated sewage (18.9%). The most common
      MLSB resistance gene was ermC. Traces of erythromycin and anhydroerythromycin (1
      ng L(-1) ) induced already resistance against clindamycin after only 10 min
      exposure. This is reported for the first time and is relevant for risk
      assessment.

PMID- 24308504
TI  - Excellent vacuum tribological properties of Pb/PbS film deposited by RF magnetron
      sputtering and ion sulfurizing.
AB  - Soft metal Pb film of 3 MUm in thickness was deposited on AISI 440C steel by RF
      magnetron sputtering, and then some of the Pb film samples were treated by low
      temperature ion sulfurizing (LTIS) and formed Pb/PbS composite film. Tribological
      properties of the Pb and Pb/PbS films were tested contrastively in vacuum and air
      condition using a self-developed tribometer (model of MSTS-1). Scanning electron
      microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy
      (XPS) were adopted to analyze the microstructure and chemical construction of the
      films and their worn surfaces. The results show that a mass of Pb was changed to
      PbS during the process of LTIS. In air condition, owing to the severe oxidation
      effect, pure Pb film showed relatively high friction coefficients (0.6), and
      Pb/PbS composite film also lost its friction-reduction property after sliding for
      a short time. In a vacuum, the average friction coefficients of Pb film were
      about 0.1, but the friction coefficient curve fluctuated obviously. And the
      Pb/PbS composite film exhibited excellent tribological properties in vacuum
      condition. Its friction coefficients keep stable at a low value of about 0.07 for
      a long time. If takes the value of friction coefficients exceeding 0.2
      continuously as a criterion of lubrication failure, the sliding friction life of
      Pb/PbS film was as long as 3.2 * 10(5) r, which is 8 times of that of the Pb
      film. It can be concluded that the Pb/PbS film has excellent vacuum tribological
      properties and important foreground for applying in space solid lubrication
      related fields. 

PMID- 24308505
TI  - Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated
      fatty acids in a transgenic oilseed crop.
AB  - Omega-3 (also called n-3) long-chain polyunsaturated fatty acids (>=C20; LC
      PUFAs) are of considerable interest, based on clear evidence of dietary health
      benefits and the concurrent decline of global sources (fish oils). Generating
      alternative transgenic plant sources of omega-3 LC-PUFAs, i.e. eicosapentaenoic
      acid (20:5 n-3, EPA) and docosahexaenoic acid (22:6 n-3, DHA) has previously
      proved problematic. Here we describe a set of heterologous genes capable of
      efficiently directing synthesis of these fatty acids in the seed oil of the crop
      Camelina sativa, while simultaneously avoiding accumulation of undesirable
      intermediate fatty acids. We describe two iterations: RRes_EPA in which seeds
      contain EPA levels of up to 31% (mean 24%), and RRes_DHA, in which seeds
      accumulate up to 12% EPA and 14% DHA (mean 11% EPA and 8% DHA). These omega-3 LC
      PUFA levels are equivalent to those in fish oils, and represent a sustainable,
      terrestrial source of these fatty acids. We also describe the distribution of
      these non-native fatty acids within C. sativa seed lipids, and consider these
      data in the context of our current understanding of acyl exchange during seed oil
      synthesis. 

PMID- 24308506
TI  - Association between a low IgE response to Phl p 5 and absence of asthma in
      patients with grass pollen allergy.
AB  - BACKGROUND: The introduction of component-resolved diagnosis was a great advance
      in diagnosis of allergy. In particular, molecular allergy techniques allowed
      investigation of the association between given molecular profiles and clinical
      expression of allergy. We evaluated the possible correlation between the level of
      specific IgE (sIgE) to single components of Phleum pratense and clinical issues
      such as the severity of allergic rhinitis (AR) and the presence or absence of
      asthma. METHODS: The study included 140 patients with rhinitis and/or asthma
      caused by sensitization to grass pollen. sIgE to Phl p 1, Phl p 5, Phl p 7, and
      Phl p 12 from Phleum pratense were measured, and the correlation between the
      stage of AR according to Allergic Rhinitis and its Impact on Asthma (ARIA)
      guidelines and the presence of asthma was studied by multivariate logistic
      regression in terms of sIgE and ARIA stage, while univariate logistic regression
      was used for IgE and a dichotomic classification of asthma as present or absent.
      RESULTS: Ten patients had intermittent AR, 48 had mild persistent AR, and 82 had
      severe persistent AR. Asthma was present in 86 patients and absent in 54. A
      significant correlation was found between severe persistent AR and presence of
      asthma (p < 0.01). The only significant correlation between clinical data and
      sIgE values was that of low values of sIgE to Phl p 5 and absence of asthma (p <
      0.01). CONCLUSIONS: This preliminary finding suggests that low values of sIgE to
      Phl p 5 are correlated with the absence of asthma in patients with grass-pollen
      induced allergy. The data, provided they are confirmed by further studies, could
      be useful when selecting patients who are candidates for allergen immunotherapy,
      since a higher risk of asthma could be used as a selection criterion for using
      this approach.

PMID- 24308507
TI  - Efficacy and tolerability of quetiapine versus haloperidol in first-episode
      schizophrenia: a randomized clinical trial.
AB  - BACKGROUND: Schizophrenia is a chronic disease of global importance. The second
      generation antipsychotic quetiapine has a favorable side-effect profile, however,
      its clinical effectiveness has been called into question when compared with first
      generation antipsychotics such as haloperidol. This study evaluates the efficacy
      and tolerability of quetiapine versus haloperidol for first-episode schizophrenia
      in the outpatient setting. METHODS: 156 adult patients with first-episode
      schizophrenia participated in an outpatient clinical trial and were randomized to
      quetiapine (200 mg/d; n = 78) or haloperidol (5 mg/d; n = 78). The study
      medications were titrated to a mean daily dose of 705 mg for quetiapeine and 14
      mg for haloperidol. The patients were assessed at baseline, six weeks, and twelve
      weeks. The primary outcome measures were positive and negative scores of the
      Positive and Negative Syndrome Scale (PANSS). Secondary measures were Global
      Assessment of Functioning (GAF) scale for overall psychosocial functioning, and
      Simpson-Angus Scale (SAS) for extra-pyramidal symptoms. RESULTS: At twelve weeks,
      the quetiapine group had a greater decrease in PANSS positive (18.9 vs. 15.3, p =
      0.013) and negative scores (15.5 vs. 11.6, p = 0.012), however, haloperidol
      showed a greater decrease in general psychopathology score (23.8 vs. 27.7, p =
      0.012). No significant difference between groups were found for total PANSS (58.3
      vs. 54.8, p = 0.24) and GAF (45.7 vs. 46.2, p = 0.79).ANOVA identified
      significant group interactions on PANSS positive (F = 18.72, df = 1.6,52.4, p <
      0.0001), negative (F = 5.20, df = 1.1,35.7, p < 0.0001), depression/anxiety (F =
      106.49, df = 1.14,37.8, p < 0.0001), and total scores (F = 7.51, df = 1.4,45.6, p
      = 0.001).SAS (8.62 vs. 0.26, p < 0.0001) and adverse events of akathisia (78% vs.
      0%, p = 0.000), parkinsonism (66.6% vs. 0%, p < 0.0001), and fatigue (84.6% vs.
      66.6%, p = 0.009) were greater in haloperidol compared to quetiapine, whereas
      headache was more common in quetiapine treated patients (11.5% vs. 35.9%, p <
      0.0001). CONCLUSIONS: Quetiapine has greater efficacy for positive and negative
      symptoms with less extra-pyramidal symptoms than haloperidol when used for first
      episode schizophrenia in the outpatient setting.

PMID- 24308508
TI  - Use of chemical indicators of beer aging for ex-post checking of storage
      conditions and prediction of the sensory stability of beer.
AB  - The rate of beer aging is affected by storage conditions including largely time
      and temperature. Although bottled beer is commonly stored for up to 1 year,
      sensorial damage of it is quite frequent. Therefore, a method for retrospective
      determination of temperature of stored beer was developed. The method is based on
      the determination of selected carbonyl compounds called as "aging indicators",
      which are formed during beer aging. The aging indicators were determined using GC
      MS after precolumn derivatization with O-(2,3,4,5,6
      pentaflourobenzyl)hydroxylamine hydrochloride, and their profile was correlated
      with the development of old flavor evolving under defined conditions
      (temperature, time) using both a mathematical and statistical apparatus. Three
      approaches, including calculation from regression graph, multiple linear
      regression, and neural networks, were employed. The ultimate uncertainty of the
      method ranged from 3.0 to 11.0  degrees C depending on the approach used.
      Furthermore, the assay was extended to include prediction of beer tendency to
      sensory aging from freshly bottled beer. 

PMID- 24308509
TI  - Using proteomic strategies for sequencing and post-translational modifications
      assignment of antigen-5, a major allergen from the venom of the social wasp
      Polybia paulista.
AB  - Antigen-5 is one of the major allergens identified in wasp venoms, and despite
      the fact that its biological function is still unknown, many studies have
      demonstrated its allergenicity. In this study, the biochemical and structural
      characterization of antigen-5 from the venom of the social wasp Polybia paulista
      are reported. A gel-based mass spectrometry strategy with CID fragmentation
      methods and classical protocols of protein chemistry, which included N- and C
      terminal sequencing, were used to assign the complete sequence and determine the
      presence/location of the post-translational modifications (PTMs) of this protein.
      Six different isoforms of antigen-5 were identified in the crude venom of P.
      paulista ; the most abundant, which corresponds to the intact form of this
      protein, was recognized by the pool of human specific-IgE. This protein was
      extensively sequenced through CID mass spectrometry, and a series of PTMs were
      observed such as hydroxylation, phosphorylation, and glycosylation. Sequence data
      revealed that this protein has 59.3-93.7% identity with antigen-5 proteins from
      other known vespid venoms. The molecular model of P. paulista antigen-5 shows
      that this protein has three alpha-helices, one 310 helix, and four beta-sheets
      covering 28 and 17.9% of the sequence, respectively. The identification and
      characterization of allergenic compounds is essential for the development of
      advanced component-resolved allergy diagnostics and treatment. 

PMID- 24308510
TI  - Second-trimester discordance and adverse perinatal outcome in twins: the STORK
      multiple pregnancy cohort.
AB  - OBJECTIVE: The aim of this study was to determine the association between
      biometry discordance at the time of the anomaly scan and adverse perinatal
      outcomes in twin pregnancies. DESIGN: Retrospective cohort study. SETTING: Nine
      hospitals in the Southwest Thames Region of London Obstetric Research
      Collaborative (STORK). POPULATION OR SAMPLE: Population multicentre retrospective
      study of all twin pregnancies booked for antenatal care in nine hospitals over a
      period of 10 years. Methods Logistic regression and receiver operating
      characteristic (ROC) curve analyses were performed to evaluate the association
      between abdominal circumference (AC) and estimated fetal weight (EFW)
      discordance, recorded between 20 and 22 weeks of gestation, and adverse pregnancy
      outcomes. MAIN OUTCOME MEASURES: Stillbirth, neonatal mortality, preterm birth
      (PTB) at <34 weeks of gestation, and birthweight (BW) discordance >=25%. RESULTS:
      A total of 2399 twin pregnancies [457 monochorionic (MC) and 1942 dichorionic
      (DC)] were included in the study. The predictive accuracy of the EFW discordance
      was poor for fetal loss after 22 weeks of gestation (area under the curve, AUC
      0.54, 95% CI 0.46-0.64), fetal loss beyond 28 weeks of gestation (AUC 0.42, 95%
      CI 0.31-0.52), perinatal loss (AUC 0.51, 95% CI 0.44-0.57), BW discordance (AUC
      0.63, 95% CI 0.56-0.65), and PTB before 34 weeks of gestation (AUC 0.52, 95% CI
      0.49-0.55). There was no significant difference in the prediction of these
      outcomes when using EFW discordance or AC discordance. CONCLUSIONS: Once
      structural malformations, chromosomal abnormalities, and twin-to-twin transfusion
      syndrome have been excluded, second-trimester EFW and AC discordance have poor
      predictive value for adverse perinatal outcomes in twin pregnancy.

PMID- 24308512
TI  - Zwitterionic polymerization to generate high molecular weight cyclic
      poly(carbosiloxane)s.
AB  - The zwitterionic ring-opening of 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane
      (TMOSC) with N-heterocyclic carbenes generates high molecular weight cyclic
      p(TMOSC). The NHC-mediated polymerization of TMOSC with 1,3-bis(2,4,6
      trimethylphenyl)imidazol-2-ylidene (IMes, 1) generates the poly(carbosiloxane)
      p(TMOSC) with molecular weights from 27,000 < Mn < 80,000 Da (1.4 < Mw/Mn < 2.2)
      within 30 min at room temp. With the more nucleophilic carbene 1,3,4,5
      tetramethyl-imidazol-2-ylidene (4), the ring-opening polymerization occurs within
      minutes at room temperature to generate cyclic p(TMOSC) with molecular weights up
      to Mn = 940,000 Da (Mw/Mn = 3.2). The resulting p(TMOSC)s are predominantly
      cyclic as evidenced by dilute solution viscosity studies and MALDI-TOF MS. DFT
      calculations provide support for both zwitterionic and neutral, cyclic
      intermediates.

PMID- 24308511
TI  - Autotransplantation of culture-positive islet product: is dirty always bad?
AB  - BACKGROUND: In selected patients, total pancreatectomy with islet
      autotransplantation (TPIAT) effectively relieves pain caused by chronic
      pancreatitis and ameliorates the brittle diabetes of the apancreatic state.
      Patients often undergo multiple endoscopic and surgical interventions prior to
      TPIAT, increasing the risk for pancreas colonization with enteric microorganisms.
      Little is known of the safety of transplanting islet cells with microbial
      contamination. METHODS: A prospectively collected database of 80 patients
      submitted to TPIAT at the Medical University of South Carolina from March 2009 to
      February 2012 was retrospectively reviewed. Patient charts were reviewed for
      postoperative infectious complications and organisms identified were compared
      with those identified in pre-transplant islet cultures. RESULTS: A total of 35
      patients (43.8%) had a positive pre-transplant islet cell Gram stain or islet
      cell culture from the final islet preparation solution. Of these 35 patients, 33
      (94.3%) were given antibiotics prophylactically post-transplant for a positive
      islet Gram stain or culture. Twenty patients (57.1%) receiving Gram stain- or
      culture-positive islets developed postoperative infectious complications, but
      only four patients (11.4%) developed infections that concorded with their pre
      transplant islet product. CONCLUSIONS: Islet transplant solutions are frequently
      culture-positive, presumably as a result of prior pancreas intervention.
      Microbial contamination of islet preparations should not preclude
      autotransplantation.

PMID- 24308513
TI  - Depression, self-esteem and anger expression patterns of Korean nursing students.
AB  - BACKGROUND: According to previous studies, nursing students' anger expression
      patterns, depression and self-esteem significantly affected the physical and
      mental well-being of patients. It is of utmost importance that the relationship
      among them is thoroughly investigated in this study. AIM: The purpose of this
      study was to examine the degrees of anger expression patterns, depression and
      self-esteem of Korean nursing students and to examine the correlations among
      them. METHODS: This was a descriptive cross-sectional study. The subjects
      consisted of 320 Korean nursing students at colleges in S and G city, Korea. The
      measurements were based on the Korean standard STAXI (State-Trait Anger
      Expression Inventory), SCL-90-R (Symptom Checklist-90-Revision) and SLCS-R (Self
      Liking/Self-Competence Scale-Revised Version). RESULTS: In the analysis of the
      degrees of variances, the subjects showed lower anger repression, anger
      expression, control of anger and depression. The degree of self-esteem revealed a
      higher than the median value. There were significant correlations among anger
      expression patterns (anger repression, anger expression and anger control),
      depression and self-esteem. LIMITATIONS: The study limitations were the degree of
      representativeness of the setting and sample, and its generalizability.
      CONCLUSION: Based on the findings of this study, interventions are needed for
      Korean nursing students in order to promote anger management and improved self
      esteem. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The development of an anger
      control programme for nursing students should focus on lowering depression and
      enhancing self-esteem. One of the policy issues focused on providing anger
      management programmes for lowering depression and enhancing self-esteem. This
      study will enable nursing students to recognize the importance of controlling
      their anger, enhancing their self-esteem, establishing positive emotions and
      improving their overall well-being as future professional nurses.

PMID- 24308514
TI  - Arabidopsis CROWDED NUCLEI (CRWN) proteins are required for nuclear size control
      and heterochromatin organization.
AB  - BACKGROUND: Plant nuclei superficially resemble animal and fungal nuclei, but the
      machinery and processes that underlie nuclear organization in these eukaryotic
      lineages appear to be evolutionarily distinct. Among the candidates for nuclear
      architectural elements in plants are coiled-coil proteins in the NMCP (Nuclear
      Matrix Constituent Protein) family. Using genetic and cytological approaches, we
      dissect the function of the four NMCP family proteins in Arabidopsis encoded by
      the CRWN genes, which were originally named LINC (LITTLE NUCLEI). RESULTS: CRWN
      proteins are essential for viability as evidenced by the inability to recover
      mutants that have disruptions in all four CRWN genes. Mutants deficient in
      different combinations of the four CRWN paralogs exhibit altered nuclear
      organization, including reduced nuclear size, aberrant nuclear shape and abnormal
      spatial organization of constitutive heterochromatin. Our results demonstrate
      functional diversification among CRWN paralogs; CRWN1 plays the predominant role
      in control of nuclear size and shape followed by CRWN4. Proper chromocenter
      organization is most sensitive to the deficiency of CRWN4. The reduction in
      nuclear volume in crwn mutants in the absence of a commensurate reduction in
      endoreduplication levels leads to an increase in average nuclear DNA density.
      CONCLUSIONS: Our findings indicate that CRWN proteins are important architectural
      components of plant nuclei that play diverse roles in both heterochromatin
      organization and the control of nuclear morphology.

PMID- 24308516
TI  - Norovirus genotypes implicated in two oyster-related illness outbreaks in
      Ireland.
AB  - We investigated norovirus (NoV) concentrations and genotypes in oyster and faecal
      samples associated with two separate oyster-related outbreaks of gastroenteritis
      in Ireland. Quantitative analysis was performed using real-time quantitative
      reverse transcription polymerase chain reaction and phylogenetic analysis was
      conducted to establish the NoV genotypes present. For both outbreaks, the NoV
      concentration in oysters was >1000 genome copies/g digestive tissue and multiple
      genotypes were identified. In faecal samples, GII.13 was the only genotype
      detected for outbreak 1, whereas multiple genotypes were detected in outbreak 2
      following the application of cloning procedures. While various genotypes were
      identified in oyster samples, not all were successful in causing infection in
      consumers. In outbreak 2 NoV GII.1 was identified in all four faecal samples
      analysed and NoV GII concentrations in faecal samples were >108 copies/g. This
      study demonstrates that a range of NoV genotypes can be present in highly
      contaminated oysters responsible for gastroenteritis outbreaks.

PMID- 24308517
TI  - Estimates of cocaine use in Milan.
AB  - A comparative analysis of three different estimation methods of cocaine use in
      Milan, Italy, is carried out, including an analysis of the size and trends of the
      underlying reference population. The three cocaine use estimates are derived from
      wastewater analysis, a "street" survey and one-source capture-recapture analysis
      of administrative sanctions for drug possession. All three data sources span
      several years during the decade 2000-2010. For each method, assumptions and
      limitations are discussed. It is concluded, although the amount of data regarding
      cocaine use in Milan during the years 2000-2010 is considerable, that none of the
      estimates is completely reliable, mainly because of the many assumptions needed
      for inference to the whole community, that all three estimates however agree on a
      substantial reduction in cocaine use and users between the years 2007 and 2010.
      The recently developed wastewater analysis technique yields estimates comparable
      to those derived from the street based survey, while capture-recapture analysis
      of administrative data on identification by law enforcement agencies as cocaine
      user probably targets only a subpopulation of all users. 

PMID- 24308518
TI  - Sizing the cannabis market: a demand-side and user-specific approach in seven
      European countries.
AB  - Demand-based estimates of total cannabis consumption rarely consider differences
      among different user types and variation across countries. To describe cannabis
      consumption patterns and estimate annual consumption for different user types
      across EU Member States, a web survey in Bulgaria, Czech Republic, Italy, the
      Netherlands, Portugal, Sweden and United Kingdom (England & Wales) collected data
      on cannabis use patterns from 3,922 persons who had consumed cannabis at least
      once in the past year. They were classified into four groups based on their
      number of use days in the past 12 months: infrequent users or chippers (<11
      days), occasional users (11-50 days), regular users (51-250 days) and intensive
      users (>250 days). User type specific data on typical amounts consumed were
      matched with data on numbers of users per user type estimated from existing
      population surveys, taking differences in mode of consumption, age and gender
      into account. Estimates were supplemented with data from populations of problem
      users to compensate for under coverage. Results showed remarkably consistent
      differences among user groups across countries. Both the average number of units
      consumed per typical use day and the average amount of cannabis consumed per unit
      increased across user types of increasing frequency of use. In all countries
      except Portugal, intensive users formed the smallest group of cannabis users but
      were responsible for the largest part of total annual cannabis consumption.
      Annual cannabis consumption varied across countries but confidence intervals were
      wide. Results are compared with previous estimates and discussed in the context
      of improving estimation methods. 

PMID- 24308515
TI  - Explaining the decline in coronary heart disease mortality in Turkey between 1995
      and 2008.
AB  - BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in
      Turkey since the early 1990s. Our study aimed to determine how much of the CHD
      mortality decrease in Turkey between 1995 and 2008 could be attributed to
      temporal trends in major risk factors and how much to advances in medical and
      surgical treatments. METHODS: The validated IMPACT CHD mortality model was used
      to combine and analyse data on uptake and effectiveness of CHD treatments and
      risk factor trends in Turkey in adults aged 35-84 years between 1995 and
      2008.Data sources were identified, searched and appraised on population,
      mortality and major CHD risk factors for adults those aged 35-84 years. Official
      statistics, electronic databases, national registers, surveys and published
      trials were screened from 1995 onwards. RESULTS: Between 1995 and 2008, coronary
      heart disease mortality rates in Turkey decreased by 34% in men and 28% in women
      35 years and over. This resulted in 35,720 fewer deaths in 2008.Approximately 47%
      of this mortality decrease was attributed to treatments in individuals (including
      approximately 16% to secondary prevention, 3% angina treatments, 9% to heart
      failure treatments, 5% to initial treatments of acute myocardial infarction, and
      5% to hypertension treatments) and approximately 42% was attributable to
      population risk factor reductions (notably blood pressure 29%; smoking 27%; and
      cholesterol 1%). Adverse trends were seen for obesity and diabetes (potentially
      increasing mortality by approximately 11% and 14% respectively). The model
      explained almost 90% of the mortality fall. CONCLUSION: Reduction in major
      cardiovascular risk factors explained approximately 42% and improvements in
      medical and surgical treatments explained some 47% of the CHD mortality fall.
      These findings emphasize the complimentary value of primary prevention and
      evidence-based medical treatments in controlling coronary heart disease.

PMID- 24308519
TI  - On illicit drug policies; methods of evaluation and comments on recent practices.
AB  - This contribution provides an overview of different approaches used to analyse
      drug policies within and across countries. Besides the great number of cost of
      illness studies which have contributed to the assessment of health harms and
      risks associated to the drug use, most of the recent efforts have focused on the
      creation of synthetic indices to classify countries around the world or to
      evaluate particular law enforcement policies in some countries. This is probably
      due to a general lack of comparable data across countries. The wide variety of
      budgetary practices in the drugs field in Europe contributes to the problems that
      exist in estimating drug-related public expenditure. These heterogeneous
      accounting practices, together with the complexity of the drug phenomenon and the
      multiplicity of perspectives on the issue, strongly constrains the possibility of
      economically evaluate and compare drug laws across countries. 

PMID- 24308520
TI  - Methods for estimating incidence of drug use: a review.
AB  - Several methods for estimating drug use incidence, that have been used in the
      literature or that could be used, having been used in a different framework, are
      described and commented. The applicability of the different methods depends on
      available data and knowledge about relevant parameters. The many similarities
      between drug use incidence estimation and estimation of disease incidence are
      highlighted, but also the distinguishing aspects that make drug use incidence
      estimation a challenge to standard statistical methods. 

PMID- 24308521
TI  - Monitoring the size and protagonists of the drug market: combining supply and
      demand data sources and estimates.
AB  - The size of the illicit drug market is an important indicator to assess the
      impact on society of an important part of the illegal economy and to evaluate
      drug policy and law enforcement interventions. The extent of illicit drug use and
      of the drug market can essentially only be estimated by indirect methods based on
      indirect measures and on data from various sources, as administrative data sets
      and surveys. The combined use of several methodologies and data sets allows to
      reduce biases and inaccuracies of estimates obtained on the basis of each of them
      separately. This approach has been applied to Italian data. The estimation
      methods applied are capture-recapture methods with latent heterogeneity and
      multiplier methods. Several data sets have been used, both administrative and
      survey data sets. First, the retail dealer prevalence has been estimated on the
      basis of administrative data, then the user prevalence by multiplier methods.
      Using information about behaviour of dealers and consumers from survey data, the
      average amount of a substance used or sold and the average unit cost have been
      estimated and allow estimating the size of the drug market. The estimates have
      been obtained using a supply-side approach and a demand-side approach and have
      been compared. These results are in turn used for estimating the interception
      rate for the different substances in term of the value of the substance seized
      with respect to the total value of the substance to be sold at retail prices. 

PMID- 24308522
TI  - Length of stay in different drug using states: lifestyles of problem and
      recreational drug consumers.
AB  - BACKGROUND: The hidden nature of the use of opioids, amphetamines, cocaine, and
      cannabis (the most commonly used and studied illicit drugs) precludes the
      accurate estimation of how many people use them and further important aspects of
      the use. Among the many aspects of drug use, the permanence times in specific
      drug using states related to the lifestyles of the various sub populations of
      users are of interest, per se, as essential components of estimates relating
      prevalence and incidence of drug use and for evaluating policies. METHODS:
      Several administrative databases and surveys collected in Italy and in different
      EU countries concerning different sub-populations of drug users were analysed to
      estimate the permanence time in a specific drug using state and the stages of a
      typical drug-using career. RESULTS: Cannabis is mostly the first illegal
      substance used. The age at onset corresponds to the very beginning of adolescence
      and various sources indicate that this onset happens earlier for men than for
      women. For problematic drug users, the switch from cannabis to heavy drugs
      happens within a rather narrow period of time, within 5-6 years from the first
      use of cannabis, along with the first episode of drug dealing. The latency period
      distribution estimated from different data sources is quite stable, with men
      presenting longer latency periods than women. CONCLUSIONS: The comparative
      analysis of several data sources allowed a more complete overview of the
      different subpopulations on the drug scene and provides interesting data to
      understand and to estimate parameters for dynamic models of drug use.

PMID- 24308523
TI  - The recent expansion in the Australian cocaine market: who are the new users and
      what are the harms?
AB  - Cocaine supplies to and within Australia increased after 2006-07, and there is
      some evidence that cocaine demand may also have risen. However, the extent,
      nature and public health implications of any changes in cocaine demand remain
      unclear. Equally unclear, is whether such changes may have been fuelled by
      declines in two of Australia's other stimulant markets. We examined general
      population trends in cocaine use and harmful practices and use of related
      stimulants between 1998 and 2010, and conducted age-period-cohort analyses using
      five repeated cross-sections of Australia's National Drug Strategy Household
      Survey. The results indicate past year cocaine use prevalence has increased
      significantly since 2004, to its highest point in the past 12 years; 2.1% in
      2010. But frequency of cocaine use has not increased. Moreover, most harmful
      practices (injecting, high-quantity use) have remained stable. Changes in the
      cocaine market appear related to changes in the Australian methamphetamine and
      ecstasy markets, including declining purity of ecstasy. For example, the cohorts
      of people most likely to exhibit recent cocaine use were also most likely to have
      used ecstasy and methamphetamine (those born from 1976 to 1984). The findings
      indicate that an increase in cocaine demand does not necessarily lead to
      substantial increases in public health harm: and indeed that the public health
      implications from the recent increase are likely to be negligible. Moreover, the
      findings suggest changes to either ecstasy or methamphetamine supply may lead to
      more shifts in demand for Australia's cocaine market. 

PMID- 24308524
TI  - The whole is just the sum of its parts: limited polydrug use among the "big
      three" expensive drugs in the United States.
AB  - Data from surveys of arrestees and the household population in the U.S. suggest
      there is only modest overlap among demand for the big three expensive illegal
      drugs (cocaine/crack, heroin, and methamphetamine). In particular, the number of
      chronic users of these substances (defined as consuming on four or more days in
      the previous month) is only about 10% below a naive estimate obtained by simply
      summing the numbers of chronic users for each of the three substances, while
      ignoring polydrug use entirely. This finding does not gainsay that polydrug use
      is common or important. One would estimate greater overlap if one adopted a more
      expansive definition of polydrug use (e.g., has the individual ever used another
      substance at any time in their life) or a more expansive list of substances
      (e.g., allowing marijuana or alcohol to count as one of the substances makes
      polydrug use seem much more common). However, it does suggest that when focusing
      on the illegal drug markets that generate the most crime, violence, and overdose
      death in the U.S., one can usefully think of three more or less separate markets
      populated at any given time by largely distinct populations of drug users. 

PMID- 24308525
TI  - Analysis of urine from pooled urinals - a novel method for the detection of novel
      psychoactive substances.
AB  - Current data on the epidemiology of recreational drug use is largely based on
      population and self-population surveys of drug use. In addition, increasingly,
      particularly for novel psychoactive substances, data collected from web
      monitoring systems is used to collect information on early trends in the use of
      NPS and the drugs available to users. All of these indicators rely on users self
      report of the drug(s) that they are using, or more accurately the drugs that they
      perceive they are using. Numerous recent studies have demonstrated significant
      variation in the content of both classical recreational drugs and novel
      psychoactive substances. The technique of waste-water analysis has allowed
      estimation of population level use of a number of established recreational drugs
      such as cocaine and MDMA. However this technique is limited for novel
      psychoactive substances because of limitations in the knowledge of the stability
      and metabolism of these compounds. Our group has developed a technique that
      involves the collection and analysis of pooled-urine from standalone portable
      urinals and demonstrated that this technique can be used to detect the use of
      both classical, established recreational drugs and novel psychoactive substances.
      We discuss this technique in this paper and the ways in which this can be further
      developed to allow detection of use of new NPS and trends in use of these
      substances over time and across geographical regions. 

PMID- 24308526
TI  - Allogeneic stem cell transplantation and targeted therapy for FLT3/ITD+ acute
      myeloid leukemia: an update.
AB  - Survival of patients with acute myelogenous leukemia (AML), particularly in
      younger patients, has improved in recent years due to improved understanding of
      disease biology, post remission therapies and supportive care. AML, however,
      remains difficult to treat as many patients will still ultimately relapse and die
      of their disease. This is particularly true in AML patients with identified FMS
      like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) molecular
      mutations, which typically confers a poor prognosis. The FLT3-ITD mutation occurs
      in about one-quarter of patients diagnosed with AML. Oftentimes, these patients
      are referred for early allogeneic hematopoietic stem cell transplantation (HSCT)
      in hopes of overcoming this poor prognostic factor. Several studies have
      demonstrated some benefit with HSCT in patients with FLT3-ITD mutation. However,
      recent data suggested that FLT3-ITD mutation remains a poor prognostic factor
      even after early HSCT; these patients remain at risk for early relapse after
      transplantation, emphasizing ongoing efforts to explore maintenance therapy with
      FLT3-ITD inhibitors in the post-transplant setting. 

PMID- 24308527
TI  - Single particle inductively coupled plasma mass spectrometry: a powerful tool for
      nanoanalysis.
AB  - Single particle inductively coupled plasma mass spectrometry is an emergent ICPMS
      method for detecting, characterizing, and quantifying nanoparticles. Although the
      number of applications reported to date is limited, the relatively simple
      instrumental requirements, the low number concentration detection levels
      attainable, and the possibility to detect both the presence of dissolved and
      particulate forms of an element make this methodology very promising in the
      nanoscience related areas. 

PMID- 24308528
TI  - Effects of intraoral aging on surface properties of coated nickel-titanium
      archwires.
AB  - OBJECTIVE: To evaluate the effects of intraoral aging on surface properties of
      esthetic and conventional nickel-titanium (NiTi) archwires. MATERIALS AND
      METHODS: Five NiTi wires were considered for this study (Sentalloy, Sentalloy
      High Aesthetic, Superelastic Titanium Memory Wire, Esthetic Superelastic Titanium
      Memory Wire, and EverWhite). For each type of wire, four samples were analyzed as
      received and after 1 month of clinical use by an atomic force microscope (AFM)
      and a scanning electronic microscope (SEM). To evaluate sliding resistance, two
      stainless steel plates with three metallic or three monocrystalline brackets,
      bonded in passive configuration, were manufactured; four as-received and
      retrieved samples for every wire were pulled five times at 5 mm/min for 1 minute
      by means of an Instron 5566, recording the greatest friction value (N). Data were
      analyzed by one-way analysis of variance and by Student's t-test. RESULTS: After
      clinical use, surface roughness increased considerably. The SEM images showed
      homogeneity for the as-received control wires; however, after clinical use
      esthetic wires exhibited a heterogeneous surface with craters and bumps. The
      lowest levels of friction were observed with the as-received Superelastic
      Titanium Memory Wire on metallic brackets. When tested on ceramic brackets, all
      the wires exhibited an increase in friction (t-test; P < .05). Furthermore, all
      the wires, except Sentalloy, showed a statistically significant increase in
      friction between the as-received and retrieved groups (t-test; P < .05).
      CONCLUSION: Clinical use of the orthodontic wires increases their surface
      roughness and the level of friction.

PMID- 24308529
TI  - Dental esthetics and quality of life in adults with severe malocclusion before
      and after treatment.
AB  - OBJECTIVE: To investigate the association between satisfaction with dental
      esthetics and quality of life, and esthetics satisfaction in relation to esthetic
      evaluations of three panel groups. MATERIALS AND METHODS: Fifty-two patients (36
      women, 16 men; age 18-61 years) with severe malocclusion were treated in Oulu
      University Hospital. Of these, 38 and 14 patients underwent orthodontic/surgical
      treatment and orthodontic treatment, respectively. A questionnaire and dental
      photographs were collected before and after treatment. The 14-item Oral Health
      Impact Profile (OHIP-14) was used to measure oral health-related quality of life.
      Satisfaction with dental esthetics was evaluated using the Visual Analogue Scale.
      Dental photographs were presented to three panel groups: 30 laypersons, 30 dental
      students, and 10 orthodontists, who rated the photographs using the Aesthetic
      Component of the Index of Orthodontic Treatment Need. RESULTS: Oral health
      related quality of life (OHIP-14 severity score) and esthetic satisfaction
      (according to the Visual Analogue Scale) improved after the treatment (P < .001).
      The most unsatisfied patients reported oral effects more often both before and
      after treatment. Changes in oral health-related quality of life components of
      severity, psychological discomfort, and psychological disability correlated
      positively with the changes in esthetic satisfaction. Orthodontists graded the
      situation before treatment as worse and the outcome as better than the
      laypersons; the level of grading by dental students fell between these two
      groups. CONCLUSION: Improvement in esthetic satisfaction due to the treatment of
      severe malocclusion improves oral health-related quality of life, particularly by
      decreasing psychological discomfort and psychological disability.

PMID- 24308530
TI  - Comparative short-term in vitro analysis of mutans streptococci adhesion on
      esthetic, nickel-titanium, and stainless-steel arch wires.
AB  - OBJECTIVE: To test the hypothesis that there are no differences in mutans
      streptococci (MS) adhesion between esthetic and metallic orthodontic arch wires
      based on their surface characteristics. MATERIALS AND METHODS: Surface roughness
      (Ra) and apparent surface free energy (SFE) were measured for six wires-four
      esthetic, one nickel-titanium (NiTi), and one stainless-steel (SS)-using
      profilometry and dynamic contact angle analysis, respectively. The amount of MS
      (Streptococcus mutans and Streptococcus sobrinus) adhering to the wires was
      quantified using the colony-counting method. The surfaces, coating layers, and MS
      adhesion were also observed by scanning electron microscopy. Statistical
      significance was set at P < .05. RESULTS: The Ra values of the esthetic wires
      were significantly different from one another depending on the coating method (P
      < .05). The NiTi wire showed the highest SFE, followed by the SS wire and then
      the four esthetic wires. The NiTi wires produced a significantly higher MS
      adhesion than did the SS wires (P < .05). The esthetic wires showed significantly
      lower MS adhesions than did the NiTi wire (P < .05). Pearson correlation analyses
      found moderate significant positive correlations between the SFE and the S mutans
      and S sobrinus adhesions (r  =  .636/.427, P < .001/P  =  .001, respectively).
      CONCLUSIONS: The hypothesis is rejected. This study indicates that some esthetic
      coatings on NiTi alloy might reduce MS adhesion in vitro in the short term.

PMID- 24308531
TI  - Comparison of the effect of minocycline and simvastatin on functional recovery
      and gene expression in a rat traumatic brain injury model.
AB  - The goal of this study was to compare the effects of minocycline and simvastatin
      on functional recovery and brain gene expression after a cortical contusion
      impact (CCI) injury. Dosage regimens were designed to provide serum
      concentrations in a rat model in the range obtained with clinically approved
      doses; minocycline 60 mg/kg q12h and simvastatin 10 mg/kg q12h for 72 h.
      Functional recovery was assessed using motor and spatial learning tasks and
      neuropathological measurements. Microarray-based transcriptional profiling was
      used to determine the effect on gene expression at 24 h, 72 h, and 7 days post
      CCI. Gene Ontology analysis (GOA) was used to evaluate the effect on relevant
      biological pathways. Both minocycline and simvastatin improved fine motor
      function, but not gross motor or cognitive function. Minocycline modestly
      decreased lesion size with no effect of simvastatin. At 24 h post-CCI, GOA
      identified a significant effect of minocycline on chemotaxis, blood circulation,
      immune response, and cell to cell signaling pathways. Inflammatory pathways were
      affected by minocycline only at the 72 h time point. There was a minimal effect
      of simvastatin on gene expression 24 h after injury, with increasing effects at
      72 h and 7 days. GOA identified a significant effect of simvastatin on
      inflammatory response at 72 h and 7 days. In conclusion, treatment with
      minocycline and simvastatin resulted in significant effects on gene expression in
      the brain reflecting adequate brain penetration without producing significant
      neurorestorative effects.

PMID- 24308532
TI  - Effect of the body wall on lithotripter shock waves.
AB  - PURPOSE: Determine the influence of passage through the body wall on the
      properties of lithotripter shock waves (SWs) and the characteristics of the
      acoustic field of an electromagnetic lithotripter. METHODS: Full-thickness ex
      vivo segments of pig abdominal wall were secured against the acoustic window of a
      test tank coupled to the lithotripter. A fiber-optic probe hydrophone was used to
      measure SW pressures, determine shock rise time, and map the acoustic field in
      the focal plane. RESULTS: Peak positive pressure on axis was attenuated roughly
      proportional to tissue thickness-approximately 6% per cm. Irregularities in the
      tissue path affected the symmetry of SW focusing, shifting the maximum peak
      positive pressure laterally by as much as ~2 mm. Within the time resolution of
      the hydrophone (7-15 ns), shock rise time was unchanged, measuring ~17-21 ns with
      and without tissue present. Mapping of the field showed no effect of the body
      wall on focal width, regardless of thickness of the body wall. CONCLUSIONS:
      Passage through the body wall has minimal effect on the characteristics of
      lithotripter SWs. Other than reducing pulse amplitude and having the potential to
      affect the symmetry of the focused wave, the body wall has little influence on
      the acoustic field. These findings help to validate laboratory assessment of
      lithotripter acoustic field and suggest that the properties of SWs in the body
      are much the same as have been measured in vitro.

PMID- 24308534
TI  - Two-dimensional interface engineering of a titania-graphene nanosheet composite
      for improved photocatalytic activity.
AB  - A graphene-based two-dimensional (2D) nanoplatform provides new opportunities for
      fabricating 2D heterojunction interfaces to fortify charge transfer in
      semiconductor assemblies. In this report, TiO2 nanosheet/graphene composite based
      2D-2D heterojunctions were fabricated by a solvothermal process. Microscopic and
      spectroscopic characterization revealed a homogeneous sheetlike morphology with
      intimate interfacial contact between the TiO2 nanosheet and graphene due to
      chemical interactions. Compared with 0D-2D Degussa P25 (TiO2)/graphene and 1D-2D
      TiO2 nanotube/graphene composites, the 2D-2D TiO2 nanosheet/graphene hybrid
      demonstrated higher photocatalytic activity toward the degradation of rhodamine B
      and 2,4-dichlorophenol under UV irradiation. Radical trapping and ESR experiments
      revealed the enhanced generation of .OH and O2(*-) in the 2D-2D heterojunction
      system. By analyzing TiO2 excited state deactivation lifetime, the interfacial
      electron transfer rates determined for 0D-2D, 1D-2D, and 2D-2D TiO2/graphene
      composites were 1.15 * 10(8) s(-1), 3.47 * 10(8) s(-1), and 1.06 * 10(9) s(-1),
      respectively. It was therefore proposed that the fast charge separation in the
      TiO2 nanosheet/graphene photocatalyst promoted the generation of reactive oxygen
      species and enhanced the photodegradation reactions. The results underscore the
      key role of nanomaterial dimensionality in interfacial charge transfer processes.

PMID- 24308535
TI  - Wisdom: a goal of nursing education.
AB  - The attainment of wisdom is a goal of intellectual development manifested in an
      individual by a solid knowledge base, effective critical thinking skills,
      creative problem solving, and a sense of duty and altruism to humankind.
      Promoting the achievement of wisdom as a focal point in a nursing program can
      provide a unifying perspective in the development of a curriculum. Teaching
      strategies such as case studies, small group discussions, mentoring, reflective
      writing, and professional networking are effective ways to promote wisdom in
      nursing students.

PMID- 24308536
TI  - Nursing students' perceptions regarding the amount and type of written feedback
      required to enhance their learning.
AB  - Effective feedback can enhance student learning, but limited evidence exists on
      whether nursing students actually use and learn from written feedback. This
      descriptive survey explored nursing students' perceptions regarding the amount
      and type of written feedback required to enhance their learning. In stage one,
      362 students completed a 28-item questionnaire regarding feedback experiences and
      preferences; in stage two, 227 students selected a preferred feedback option for
      a final topic assignment. Findings revealed that many of the students wished to
      be engaged with the feedback process and believed effective written feedback can
      and does enhance their learning. However many students also reported learning
      barriers-including absent, inadequate, ambiguous, inconsistent, and ineffective
      feedback-indicating a significant disconnect between desired and actual feedback.
      Recommendations include a greater focus on engaging nursing students in the
      feedback process and evaluating the effectiveness of written feedback for
      individual students.

PMID- 24308537
TI  - Journey toward integration of simulation in a baccalaureate nursing curriculum.
AB  - Simulation is increasingly being used as a teaching strategy in nursing
      education. The best learning outcomes occur when simulation is integrated into
      the curriculum rather than added to a crowded curriculum. Faculty are challenged
      to integrate simulation experiences into the curriculum in a way that promotes
      optimal achievement of student learning objectives. The purpose of this article
      is to describe the journey toward the integration of simulation in a
      baccalaureate nursing curriculum. A description of the journey from the
      beginning, through Health Resources and Services Administration funding, as a
      participating site in The NCSBN National Simulation Study, and through curricular
      redesign are presented in the context of faculty growth and lessons learned. The
      ultimate purpose is to provide guidance to faculty teaching in nursing programs
      that may be struggling with some of the same issues that beleaguered faculty
      during our journey.

PMID- 24308538
TI  - What do nursing students learn about patient safety? an integrative literature
      review.
AB  - Preventing adverse events and enhancing patient safety in health care are key
      objectives of nursing education. This integrative literature review critically
      appraises the content of patient safety in prelicensure nursing education, the
      teaching and learning methods used, and subsequent nursing student learning. The
      studies (N = 20) reviewed reveal that patient safety in nursing curricula was not
      necessarily obvious. However, patient safety was taught within both academic
      settings and clinical environments. The identified content of patient safety was
      learning from errors, responsible individual and interprofessional team working,
      anticipatory action in complex environments, and patient safety-centered nursing.
      The teaching and learning methods used included combining multiple methods.
      Patient safety curricula included continuing improvement in patient safety
      competency, sensitivity to nursing students' role, and having a supportive
      learning environment. Patient safety in the nursing curriculum requires broad,
      comprehensive attention and development as a specific theme with an
      interprofessional approach.

PMID- 24308539
TI  - Systematic genomic identification of colorectal cancer genes delineating advanced
      from early clinical stage and metastasis.
AB  - BACKGROUND: Colorectal cancer is the third leading cause of cancer deaths in the
      United States. The initial assessment of colorectal cancer involves clinical
      staging that takes into account the extent of primary tumor invasion, determining
      the number of lymph nodes with metastatic cancer and the identification of
      metastatic sites in other organs. Advanced clinical stage indicates metastatic
      cancer, either in regional lymph nodes or in distant organs. While the genomic
      and genetic basis of colorectal cancer has been elucidated to some degree, less
      is known about the identity of specific cancer genes that are associated with
      advanced clinical stage and metastasis. METHODS: We compiled multiple genomic
      data types (mutations, copy number alterations, gene expression and methylation
      status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We
      used an elastic-net regularized regression method on the combined genomic data to
      identify genetic aberrations and their associated cancer genes that are
      indicators of clinical stage. We ranked candidate genes by their regression
      coefficient and level of support from multiple assay modalities. RESULTS: A fit
      of the elastic-net regularized regression to 197 samples and integrated analysis
      of four genomic platforms identified the set of top gene predictors of advanced
      clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were
      identified robustly in bootstrap resampling analysis. CONCLUSIONS: We conducted
      an analysis integrating multiple genomic features including mutations, copy
      number alterations, gene expression and methylation. This integrated approach in
      which one considers all of these genomic features performs better than any
      individual genomic assay. We identified multiple genes that robustly delineate
      advanced clinical stage, suggesting their possible role in colorectal cancer
      metastatic progression.

PMID- 24308533
TI  - Retinoic acid actions through mammalian nuclear receptors.

PMID- 24308541
TI  - Chemical dynamics of the first proton-coupled electron transfer of water
      oxidation on TiO2 anatase.
AB  - Titanium dioxide (TiO2) is a prototype, water-splitting (photo)catalyst, but its
      performance is limited by the large overpotential for the oxygen evolution
      reaction (OER). We report here a first-principles density functional theory study
      of the chemical dynamics of the first proton-coupled electron transfer (PCET),
      which is considered responsible for the large OER overpotential on TiO2. We use a
      periodic model of the TiO2/water interface that includes a slab of anatase TiO2
      and explicit water molecules, sample the solvent configurations by first
      principles molecular dynamics, and determine the energy profiles of the two
      electronic states involved in the electron transfer (ET) by hybrid functional
      calculations. Our results suggest that the first PCET is sequential, with the ET
      following the proton transfer. The ET occurs via an inner sphere process, which
      is facilitated by a state in which one electronic hole is shared by the two
      oxygen ions involved in the transfer. 

PMID- 24308540
TI  - The effects of oral garlic on vaginal candida colony counts: a randomised placebo
      controlled double-blind trial.
AB  - OBJECTIVE: Garlic is effective against Candida species in vitro, and along with
      other alternative therapies, is used by women with vulvovaginal candidiasis. The
      objective of this study was to ascertain whether oral garlic reduced vaginal
      candida counts during the second half of the menstrual cycle in asymptomatic
      women colonised with Candida species. DESIGN: A simple randomised double-blinded
      controlled trial. SETTING: Melbourne, Australia. SAMPLE: Sixty-three asymptomatic
      women who were culture-positive for Candida species at screening. METHODS:
      Participants were randomised to three garlic tablets or placebo orally, twice
      daily, for 14 days. MAIN OUTCOME MEASURES: The primary outcome was the proportion
      of women with colony counts of candida >100 colony-forming units per ml in any
      given day during the last 7 days before menstruation, defined as a 'case'.
      Secondary outcomes included the mean quantitative colony counts of candida over
      14 days prior to menses. RESULTS: There was no evidence of a difference between
      the proportion of cases in the garlic and placebo groups (76 versus 90%; relative
      risk, RR 0.85; 95% confidence interval, 95% CI 0.67-1.08), in the mean colony
      counts in both groups (ratio of geometric means of candidal colony counts 0.63;
      95% CI 0.39-10.03; P = 0.74), or difference in the number of women reporting
      abnormal vaginal symptoms during the 2 weeks before menstruation (RR 1.03; 95% CI
      0.67-1.58; P = 0.91). The garlic group reported more adverse effects (83%
      compared 43% in the placebo group; difference in proportions 39%; 95% CI 17-%; P
      < 0.01). CONCLUSIONS: This study provided data for sample size calculations in
      future studies on the antifungal effect of garlic, but provided no evidence to
      inform clinical practice regarding the use of garlic in vaginal candidiasis.
      Further studies might investigate longer courses or topical formulations.

PMID- 24308543
TI  - Ex vivo expansion of hematopoietic stem- and progenitor cells from cord blood in
      coculture with mesenchymal stroma cells from amnion, chorion, Wharton's jelly,
      amniotic fluid, cord blood, and bone marrow.
AB  - In most cases, the amount of hematopoietic stem and progenitor cells (HSPCs) in a
      single cord blood (CB) unit is not sufficient for allogenic transplantation of
      adults. Therefore, two CB units are usually required. The ex vivo expansion of
      HSPCs from CB in coculture with mesenchymal stroma cells (MSCs) might be an
      alternative. It was investigated, whether bone marrow-derived MSCs, which have to
      be obtained in an invasive procedure, introduce a further donor and increases the
      risk of transmissible infectious diseases for the patient can be replaced by MSCs
      from amnion, chorion, Wharton's jelly, amniotic fluid, and CB, which can be
      isolated from placental tissue which is readily available when CB is sampled. In
      a two-step ex vivo coculture mononuclear cells from cryopreserved CB were
      cultured with different MSC-feederlayers in a medium supplemented with cytokines
      (stem cell factor, thrombopoietin [TPO], and granulocyte colony-stimulating
      factor). Expansion rates were analyzed as well, by long-term culture-initiating
      cell (LTC-IC) and colony-forming unit (CFU) assays, as by measuring CD34(+)- and
      CD45(+)-cells. Due to the comparably low number of 5*10(2) to 1*10(4) CD34(+)
      cells per cm(2) MSC-monolayer, we observed comparably high expansion rates from
      80 to 391,000 for CFU, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)
      cells. Expansion of LTC-IC was partly observed. Compared to the literature, we
      found a better expansion rate of CD34(+)-cells with MSCs from all different
      sources. This is probably due to the comparably low number of 5*10(2) to 1*10
      CD34(+)-cells per cm(2) MSC-monolayer we used. Comparably, high expansion rates
      were observed from 80 to 391,000 for CFUs, 70 to 313,000 for CD34(+)-, and 200 to
      352,000 for CD45(+)-cells. However, the expansion of CD34(+)-cells was
      significantly more effective with MSCs from bone marrow compared to MSCs from
      amnion, chorion, and Wharton's jelly. The comparison of MSCs from bone marrow
      with MSCs from CB and amniotic fluid showed no significant difference. We
      conclude that MSCs from placental tissues might be useful in the expansion of
      HSPCs, at least if low numbers of CD34(+)-cells per cm(2) MSC-monolayer and a
      high TPO concentration are implemented in the expansion culture. 

PMID- 24308542
TI  - Brain morphology in children with 47, XYY syndrome: a voxel- and surface-based
      morphometric study.
AB  - The neurocognitive and behavioral profile of individuals with 47,XYY is
      increasingly documented; however, very little is known about the effect of a
      supernumerary Y-chromosome on brain development. Establishing the neural
      phenotype associated with 47,XYY may prove valuable in clarifying the role of Y
      chromosome gene dosage effects, a potential factor in several neuropsychiatric
      disorders that show a prevalence bias toward males, including autism spectrum
      disorders. Here, we investigated brain structure in 10 young boys with 47,XYY and
      10 age-matched healthy controls by combining voxel-based morphometry (VBM) and
      surface-based morphometry (SBM). The VBM results show the existence of altered
      gray matter volume (GMV) in the insular and parietal regions of 47,XYY relative
      to controls, changes that were paralleled by extensive modifications in white
      matter (WM) bilaterally in the frontal and superior parietal lobes. The SBM
      analyses corroborated these findings and revealed the presence of abnormal
      surface area and cortical thinning in regions with abnormal GMV and WMV. Overall,
      these preliminary results demonstrate a significant impact of a supernumerary Y
      chromosome on brain development, provide a neural basis for the motor, speech and
      behavior regulation difficulties associated with 47,XYY and may relate to sexual
      dimorphism in these areas. 

PMID- 24308546
TI  - Effect of pH on the complexation of kaempferol-4'-glucoside with three beta
      cyclodextrin derivatives: isothermal titration calorimetry and spectroscopy
      study.
AB  - The utilization of kaempferol and its glycosides in food and pharmaceutical
      industries could be improved by the formation of inclusion complexes with
      cyclodextrins at different pH. This study explores the complexation of kaempferol
      4'-glucoside with sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD), hydroxypropyl
      beta-cyclodextrin (HP-beta-CD), and methylated-beta-cyclodextrin (M-beta-CD) in
      phosphate buffer solutions of different pH using isothermal titration
      calorimetry, UV-vis absorption and proton nuclear magnetic resonance spectroscopy
      at 298.2 K. Experimental results showed that kaempferol-4'-glucoside binds with
      the three beta- cyclodextrins in the same 1:1 stoichiometry. The rank order of
      stability constants is SBE-beta-CD > HP-beta-CD > M-beta-CD at the same pH level
      and pH 6.0 > pH 7.4 > pH 9.0 for the same cyclodextrin. The binding of kaempferol
      4'-glucoside with the three beta-cyclodextrin derivatives is synergistically
      driven by enthalpy and entropy at pH 6.0 and enthalpy-driven at pH 7.4 and 9.0.
      The possible inclusion mode was that in the cavity of beta-CD is included the
      planar benzopyranic-4-one part of the kaempferol-4'-glucoside. 

PMID- 24308545
TI  - Serum IGFBP2 and MSLN as diagnostic and prognostic biomarkers for pancreatic
      cancer.
AB  - BACKGROUND: Identification of diagnostic and prognostic biomarkers is a research
      priority for the improved management of pancreatic ductal adenocarcinoma (PDAC).
      Insulin-like growth factor binding protein 2 (IGFBP2) and mesothelin (MSLN) have
      shown potential as serum biomarkers in other cancers, but have not been
      adequately studied in PDAC. METHODS: Serum IGFBP2 and MSLN levels were quantified
      by enzyme-linked immunosorbent assay (ELISA) in a cohort of 84 PDAC patients, 84
      healthy control subjects and 40 chronic pancreatitis (ChPT) patients. Regression
      models related IGFBP2 and MSLN levels to diagnosis, gender, age, stage and
      survival. RESULTS: IGFPB2 and MSLN serum levels were diagnostic for PDAC in age
      adjusted models (P = 0.032 and P = 0.002, respectively) when compared with ChPT
      and healthy control samples. At a 95% specificity threshold, the sensitivity for
      IGFBP2 was 22% and the sensitivity for MSLN was 17%. Neither protein approached
      the diagnostic accuracy of CA 19-9. However, IGFBP2 or MSLN or both correctly
      identified 18 of the 28 samples misidentified by CA 19-9. In age-adjusted models,
      neither serum IGFBP2 (P = 0.36) nor MSLN (P = 0.29) were significant predictors
      of survival. DISCUSSION: Serum IGFBP2 and MSLN are weak diagnostic classifiers
      individually, but may be useful in a diagnostic biomarker panel.

PMID- 24308547
TI  - Patterned friction and cell attachment on schizophobic polyelectrolyte surfaces.
AB  - A series of copolyelectrolytes with randomly positioned fluorinated (hydrophobic)
      and zwitterionic (hydrophilic) repeat units was synthesized and used to assemble
      multilayers. Regular layer-by-layer growth was observed for polymers with a
      charge density as low as 6%. The hydrophobicity of these "schizophobic" surfaces
      increased with increasing fluorine content. Polymer-on-polymer stamping was used
      to create patterned areas of low and high friction, probed by lateral force
      microscopy using a modified hydrophobic tip. "Contractile" A7r5 smooth muscle
      cells adhered to the fluorinated surfaces, but the introduction of zwitterion
      functionality induced a motile, less firmly attached morphology consistent with
      the "synthetic" motile phenotype of this cell line. In contrast with cells well
      adhered (on fluorinated) or completely nonadhering (on zwitterionic) films,
      incorporation of closely spaced repeat units with strongly contrasting
      hydrophobicity appears to generate intermediate cell adhesion behavior. 

PMID- 24308548
TI  - Methadone treatment providers' views of drug court policy and practice: a case
      study of New York State.
AB  - BACKGROUND: Specialized drug treatment courts are a central part of drug-related
      policy and programs in the United States and increasingly outside the U.S. While
      in theory they offer treatment as a humane and pragmatic alternative to arrest
      and incarceration for certain categories of drug offenses, they may exclude some
      forms of treatment-notably methadone maintenance treatment (MMT). We sought to
      understand from the perspective of treatment providers whether this exclusion
      existed and was of public health importance in New York State as a case example
      of a state heavily committed to drug courts and with varying court-level policies
      on MMT. Drug courts have been extensively evaluated but not with respect to
      exclusion of MMT and not from the perspective of treatment providers. METHODS:
      Qualitative structured interviews of 15 providers of MMT and 4 NGO advocates in
      counties with diverse court policies on MMT, with content analysis. RESULTS:
      Courts in some counties require MMT patients to "taper off" methadone in an
      arbitrary period or require that methadone be a "bridge to abstinence". Treatment
      providers repeatedly noted that methadone treatment is stigmatized and poorly
      understood by some drug court personnel. Some MMT providers feared court
      practices were fueling non-medical use of prescription opiates. CONCLUSIONS: Drug
      court practices in some jurisdictions are a barrier to access to MMT and may
      constitute discrimination against persons in need of MMT. These practices should
      be changed, and drug courts should give high priority to ensuring that treatment
      decisions are made by or in close consultation with qualified health
      professionals.

PMID- 24308549
TI  - Impact of traumatic dental injuries among adolescents on family's quality of
      life: a population-based study.
AB  - AIM: To evaluate the impact of traumatic dental injury (TDI) among Brazilian
      adolescents on their families' quality of life (QoL). DESIGN: A cross-sectional
      study was carried out with a population-based sample of 1122 schoolchildren aged
      11-14 years selected using a multistage sampling procedure. Parents/caregivers
      answered the Brazilian version of the 14-item Family Impact Scale (B-FIS) to
      assess the impact on family's QoL. The main independent variable was TDI, which
      was diagnosed using the Andreasen classification. Malocclusion, dental caries,
      gender and socio-economic classification were the other independent variables.
      Poisson regression analyses were carried out (P<0.05). RESULTS: The prevalence of
      TDI was 14.8%. The multivariate model demonstrated that families of adolescents
      diagnosed with fracture involving the dentine or dentine/pulp were more likely to
      report a negative impact on the overall B-FIS score [rate ratio (RR)=1.44; 95%
      confidence interval (CI): 1.10-1.88] as well on the Parental/Family Activity
      (RR=1.45; 95% CI: 1.09-1.94), Parental Emotions (RR=1.45; 95% CI: 1.03-2.04) and
      Family Conflict (RR=1.46; 95% CI: 1.01-2.11) subscales in comparison with those
      who had no signs of TDI. CONCLUSIONS: Families of adolescents with more severe
      TDI were more likely to report a negative impact on QoL, affecting family
      activities and emotions, which can result in family conflicts.

PMID- 24308550
TI  - The association between hyperuricemia and betel nut chewing in Taiwanese men: a
      cross-sectional study.
AB  - BACKGROUND: Studies have associated betel nut chewing with cancers, metabolic
      syndrome, cardiovascular disorders, chronic kidney disease, and proteinuria. This
      study investigated whether hyperuricemia is associated with betel nut chewing in
      men who participated in a health check-up program. METHODS: From hospital
      records, we identified a total of 11,991 men who participated in the health check
      up program from 2003 to 2009. They were divided into hyperuricemic group and non
      hyperuricemic group. Laboratory tests, medical history, and status of cigarette
      smoking, alcohol consumption, and betel nut chewing were compared between the 2
      groups. We calculated odds ratio (OR) and 95% confidence interval (CI) of
      hyperuricemia in association with betel nut consumption and other factors.
      RESULTS: Compared with the non-hyperuricemic group, the hyperuricemic group was
      slightly older (59.4 vs. 58.6 years) but less prevalent with betel nut use (11.8
      vs. 13.6%, p = 0.003). Multivariable logistic regression analysis showed that
      hyperuricemia was negatively associated with betel nut chewing (OR 0.75, 95% CI
      0.66-0.84), older age (OR 0.84, 95% CI 0.77-0.93), and diabetes mellitus (OR
      0.57, 95% CI 0.50-0.64). On the other hand, hyperuricemia was positively
      associated with body mass index (OR 1.75, 95% CI 1.62-1.90), drinking (OR 1.36,
      95% CI 1.25-1.49), hypertension (OR 1.41, 95% CI 1.30-1.52), mixed hyperlipidemia
      (OR 1.84, 95% CI 1.33-2.54), chronic kidney disease (OR 3.28, 95% CI 2.94-3.65),
      and proteinuria (OR 1.22, 95% CI 1.08-1.38). Smoking, hypercholesterolemia, and
      hypertriglyceridemia had no significant association with hyperuricemia.
      CONCLUSION: Our data suggest that betel nut chewing is negatively associated with
      hyperuricemia.

PMID- 24308552
TI  - Proteomics for the discovery of biomarkers and diagnosis of periodontitis: a
      critical review.
AB  - Periodontitis is a common chronic and destructive disease whose pathogenetic
      mechanisms remain unclear. Due to their sensitivity and global scale, proteomics
      studies offer the opportunity to uncover critical host and pathogen activity
      indicators and can elucidate clinically applicable biomarkers for improved
      diagnosis and treatment of the disease. This review summarizes the literature of
      proteomics studies on periodontitis and comprehensively discusses commonly found
      candidate biomarkers. Key considerations in the design of an experimental
      proteomics platform are also outlined. The applicability of protein biomarkers
      across the progression of periodontitis and unexplored areas of research are
      highlighted. 

PMID- 24308553
TI  - Using proteomics to identify the HBx interactome in hepatitis B virus: how can
      this inform the clinic?
AB  - Hepatitis B virus (HBV) is a small and enveloped DNA virus, of which chronic
      infection is the main risk factor of liver cirrhosis and hepatocellular
      carcinoma. Hepatitis B virus X protein (HBx) is a multifunctional protein encoded
      by HBV genome, which have significant effects on HBV replication and
      pathogenesis. Through directly interacting with cellular proteins, HBx is capable
      to promote HBV replication, regulate transcription of host genes, disrupt protein
      degradation, modulate signaling pathway, manipulate cell death and deregulate
      cell cycle. In this review, we briefly discuss the diversified effects of HBx
      interactome and their potential clinical significances. 

PMID- 24308551
TI  - Survey of the total fatty acid and triacylglycerol composition and content of 30
      duckweed species and cloning of a Delta6-desaturase responsible for the
      production of gamma-linolenic and stearidonic acids in Lemna gibba.
AB  - BACKGROUND: Duckweeds, i.e., members of the Lemnoideae family, are amongst the
      smallest aquatic flowering plants. Their high growth rate, aquatic habit and
      suitability for bio-remediation make them strong candidates for biomass
      production. Duckweeds have been studied for their potential as feedstocks for
      bioethanol production; however, less is known about their ability to accumulate
      reduced carbon as fatty acids (FA) and oil. RESULTS: Total FA profiles of thirty
      duckweed species were analysed to assess the natural diversity within the
      Lemnoideae. Total FA content varied between 4.6% and 14.2% of dry weight whereas
      triacylglycerol (TAG) levels varied between 0.02% and 0.15% of dry weight. Three
      FA, 16:0 (palmitic), 18:2Delta9,12 (Linoleic acid, or LN) and 18:3Delta9,12,15
      (alpha-linolenic acid, or ALA) comprise more than 80% of total duckweed FA. Seven
      Lemna and two Wolffiela species also accumulate polyunsaturated FA containing
      Delta6-double bonds, i.e., GLA and SDA. Relative to total FA, TAG is enriched in
      saturated FA and deficient in polyunsaturated FA, and only five Lemna species
      accumulate Delta6-FA in their TAG. A putative Delta6-desaturase designated LgDes,
      with homology to a family of front-end Delta6-FA and Delta8-spingolipid
      desaturases, was identified in the assembled DNA sequence of Lemna gibba.
      Expression of a synthetic LgDes gene in Nicotiana benthamiana resulted in the
      accumulation of GLA and SDA, confirming it specifies a Delta6-desaturase.
      CONCLUSIONS: Total accumulation of FA varies three-fold across the 30 species of
      Lemnoideae surveyed. Nine species contain GLA and SDA which are synthesized by a
      Delta6 front-end desaturase, but FA composition is otherwise similar. TAG
      accumulates up to 0.15% of total dry weight, comparable to levels found in the
      leaves of terrestrial plants. Polyunsaturated FA is underrepresented in TAG, and
      the Delta6-FA GLA and SDA are found in the TAG of only five of the nine Lemna
      species that produce them. When present, GLA is enriched and SDA diminished
      relative to their abundance in the total FA pool.

PMID- 24308554
TI  - Quantifying the risk of respiratory infection in healthcare workers performing
      high-risk procedures.
AB  - This study determined the risk of respiratory infection associated with high-risk
      procedures (HRPs) performed by healthcare workers (HCWs) in high-risk settings.
      We prospectively studied 481 hospital HCWs in China, documented risk factors for
      infection, including performing HRPs, measured new infections, and analysed
      whether HRPs predicted infection. Infection outcomes were clinical respiratory
      infection (CRI), laboratory-confirmed viral or bacterial infection, and an
      influenza infection. About 12% (56/481) of the study participants performed at
      least one HRP, the most common being airway suctioning (7.7%, 37/481). HCWs who
      performed a HRP were at significantly higher risk of developing CRI and
      laboratory-confirmed infection [adjusted relative risk 2.9, 95% confidence
      interval (CI) 1.42-5.87 and 2.9, 95% CI 1.37-6.22, respectively]. Performing a
      HRP resulted in a threefold increase in the risk of respiratory infections. This
      is the first time the risk has been prospectively quantified in HCWs, providing
      data to inform occupational health and safety policies.

PMID- 24308555
TI  - Variability of subseafloor viral abundance at the geographically and geologically
      distinct continental margins.
AB  - We studied the relationship between viral particle and microbial cell abundances
      in marine subsurface sediments from three geographically distinct locations in
      the continental margins (offshore of the Shimokita Peninsula of Japan, the
      Cascadia Margin off Oregon, and the Gulf of Mexico) and found depth variations in
      viral abundances among these sites. Viruses in sediments obtained offshore of the
      Shimokita and in the Cascadia Margin generally decreased with increasing depth,
      whereas those in sediments from the Gulf of Mexico were relatively constant
      throughout the investigated depths. In addition, the abundance ratios of viruses
      to microbial cells notably varied among the sites, ranging between 10(-3) and
      10(1) . The subseafloor viral abundance offshore of the Shimokita showed a
      positive relationship with the microbial cell abundance and the sediment
      porosity. In contrast, no statistically significant relationship was observed in
      the Cascadia Margin and the Gulf of Mexico sites, presumably due to the long-term
      preservation of viruses from enzymatic degradation within the low-porosity
      sediments. Our observations indicate that viral abundance in the marine
      subsurface sedimentary environment is regulated not only by in situ production
      but also by the balance of preservation and decay, which is associated with the
      regional sedimentation processes in the geological settings. 

PMID- 24308556
TI  - Polymers with dual light-triggered functions of shape memory and healing using
      gold nanoparticles.
AB  - Shape-memory and stimuli-healable polymers (SMP and SHP) are two types of
      emerging smart materials. Among the many stimuli that can be used to control SMP
      and SHP, light is unique because of its unparalleled remote activation and
      spatial control. Generally, light-triggered shape memory and optically healable
      polymers are different polymers and it is challenging to endow the same polymer
      with the two light-triggered functions because of their structural
      incompatibility. In this paper, we describe a general polymer design that allows
      a single material to exhibit both light-controlled shape memory and optical
      healing capabilities. We show that by chemically cross-linking a crystalline
      polymer and loading it with a small amount of gold nanoparticles (AuNPs), the
      polymer displays optically controllable shape memory and fast optical healing
      based on the same localized heating effect arising from the surface plasmon
      resonance of AuNPs. The photothermal effect controls, on the one hand, the shape
      memory process by tuning the temperature with respect to Tm of the crystalline
      phase and, on the other hand, activates the damage healing through crystal
      melting and recrystallization. Moreover, we show that these two features can be
      triggered separately in a sequential manner. 

PMID- 24308557
TI  - Editorial comment for Shiyong et al.

PMID- 24308558
TI  - Pariser-Parr-Pople model based investigation of ground and low-lying excited
      states of long acenes.
AB  - Several years ago, Angliker et al. [ Chem. Phys. Lett. 1982 , 87 , 208 ]
      predicted nonacene to be the first linear acene with the triplet state 1(3)B2u as
      the ground state, instead of the singlet 1(1)Ag state. However, contrary to that
      prediction, in a recent experimental work, Tonshoff and Bettinger [ Angew. Chem.
      Int. Ed. 2010 , 49 , 4125 ] demonstrated that nonacene has a singlet ground
      state. Motivated by this experimental finding, we decided to perform a systematic
      theoretical investigation of the nature of the ground and the low-lying excited
      states of long acenes, with an emphasis on the singlet-triplet gap, starting from
      naphthalene, all the way up to decacene. The methodology adopted in our work is
      based upon the Pariser-Parr-Pople model (PPP) Hamiltonian, along with the large
      scale multireference singles-doubles configuration interaction (MRSDCI) approach.
      Our results predict that even though the singlet-triplet gap decreases with the
      increasing conjugation length, nevertheless, it remains finite till decacene,
      thus providing no evidence of the predicted singlet-triplet crossover. We also
      analyze the nature of many-particle wave function of the correlated singlet
      ground state and find that the longer acenes exhibit a tendency toward an open
      shell singlet ground state. Moreover, when we compare the experimental absorption
      spectra of octacene and nonacene with their calculated singlet and triplet
      absorption spectra, we observe excellent agreement for the singlet case. Hence,
      the optical absorption results also confirm the singlet nature of the ground
      state for longer acenes. Calculated triplet absorption spectra of acenes predict
      two well-separated intense long-axis polarized absorptions, against one such peak
      observed for the singlet case. This is an important prediction regarding the
      triplet optics of acenes, which can be tested in future experiments on oriented
      samples. 

PMID- 24308560
TI  - Lung reaeration and reventilation after aspiration of pleural effusions. A study
      using electrical impedance tomography.
AB  - RATIONALE: Lung reexpansion after pleural effusion aspiration is composed of
      reaeration and reventilation. Previous studies evaluated only the immediate
      reaeration, and the reventilation was not evaluated using a direct lung
      ventilation measurement method. Also, indirect evidence indicates that the
      effusion could cause ventilator asynchrony between the lungs. The electrical
      impedance tomography can directly and reliably measure lung reaeration,
      reventilation, and synchrony. OBJECTIVES: To evaluate lung reaeration,
      reventilation, and ventilator synchrony before and over 1 hour after a pleural
      aspiration. METHODS: A prospective and observational study using electrical
      impedance tomography to measure the lung reaeration, reventilation, and
      ventilatory synchrony between the lungs (through phase angle) before and over 1
      hour after the pleural aspiration of 22 patients with unilateral malignant
      effusions. MEASUREMENTS AND MAIN RESULTS: The ipsilateral (affected by the
      effusion) (P < 0.001) and contralateral (P = 0.008) lung reaerated immediately
      without further reaeration over the next hour. However, the reventilation
      response was heterogeneous, with patients increasing, maintaining, or decreasing
      ipsilateral lung ventilation after the aspiration. The pleural effusion had
      caused ventilatory asynchrony (93 +/- 71 degrees) that was immediately reversed
      by the aspiration. In some patients, the asynchrony was so extreme that one lung
      was inflating while the other was deflating, causing paradoxical ventilation.
      CONCLUSIONS: After a pleural effusion aspiration, the ipsilateral and
      contralateral lungs reaerate immediately without further reaeration over the next
      hour. The reventilation shows a heterogeneous response, with patients increasing,
      maintaining, or decreasing the ipsilateral lung ventilation. The pleural effusion
      causes a ventilatory asynchrony between the lungs that is immediately decreased
      by the aspiration. In some patients, that asynchrony is so intense that it causes
      paradoxical ventilation.

PMID- 24308559
TI  - Prodromal posterior cortical atrophy: clinical, neuropsychological, and
      radiological correlation.
AB  - We present longitudinal clinical, cognitive, and neuroimaging data from a 63-year
      old woman who enrolled in research as a normal control and evolved posterior
      cortical atrophy (PCA) over 5 year follow-up. At baseline she reported only
      subtle difficulty driving and performed normally on cognitive tests, but already
      demonstrated atrophy in left visual association cortex. With follow-up she
      developed insidiously progressive visuospatial and visuoperceptual deficits,
      correlating with progressive atrophy in bilateral visual areas. Amyloid PET was
      positive. This case tracks the evolution of PCA from the prodromal stage, and
      illustrates challenges to early diagnosis as well as the utility of imaging
      biomarkers. 

PMID- 24308561
TI  - Serological identification of URGCP as a potential biomarker for glioma.
AB  - AIM: Glioblastoma multiforme (GBM) is one of the most frequent human brain tumor
      and causes dismal outcome. To identify tumor-associated antigens in GBM patients
      may find potential diagnostic markers and immunotherapeutic targets. In this
      study, we identified a gene termed URGCP using the serological identification of
      antigens by recombinant A2B5 positive glioma cDNA library. The gene product of
      URGCP is immunogenic in GBM after tested in allogenic patients serum screening.
      METHODS AND RESULTS: GBM patients with an auto-antibody response against URGCP
      show longer survival than those without URGCP response. In additional, we show
      that URGCP was high expression in most GBM tissues and cell lines compared with
      normal brain tissues and majorly co-expressed with stem cell marker A2B5.
      CONCLUSION: We identified a potential new biomarker of GBM, URGCP. The findings
      indicate that URGCP is immunogenic in human GBM and suggest its potential use as
      diagnostic and immunotherapeutic for GBM patients.

PMID- 24308562
TI  - Oxidative cleavage-based near-infrared fluorescent probe for hypochlorous acid
      detection and myeloperoxidase activity evaluation.
AB  - A near-infrared (NIR) fluorescent probe was synthesized and demonstrated to be
      highly selective in reaction with hypochlorous acid (HOCl), an endogenous
      reactive oxygen species (ROS) produced by myeloperoxidase in neutrophils. The
      reaction with HOCl resulted in the NIR fluorescence quenching at 774 nm and the
      absorbance decreasing at 710 nm, accompanied by the appearance of a new
      absorption band at 520 nm. The reaction mechanism was carefully examined and
      proposed to proceed by initial formation of chlorohydrins and subsequent
      degradation. This NIR fluorescent probe was successfully applied as a selective
      and sensitive indicator for HOCl on the basis of either colorimetry or
      fluorometry, which showed detection limits of 0.13 and 0.70 MUM, respectively. In
      addition, the molecular probe was further demonstrated for NIR fluorescence
      imaging of HOCl in cells and for evaluating the enzymatic activity of
      myeloperoxidase in the HOCl generation by measuring absorbance change. 

PMID- 24308563
TI  - Citrus peel extract attenuates acute cyanide poisoning-induced seizures and
      oxidative stress in rats.
AB  - The primary aimed of this study was to investigate the potential protective
      effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN)
      poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50
      value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly
      increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre
      administered for 1, 2 and 3 days, respectively, in rats in a time-dependent
      manner. Intraperitoneal injection of the sublethal dose of KCN (3 mg/Kg bwt) into
      rats increased, 24 hrs later, lipid peroxidation (LPO), nitric oxide (NO),
      glutamate levels and acetylcholinesterase (AChE) activity in hippocampus,
      striatum and cerebral cortex. KCN also decreased brain glutathione (GSH) level
      and superoxide dismutase (SOD) and catalase (CAT) activities in these animals.
      Pre-treatment of rats with MECP inhibited KCN-induced increases in LPO, NO, and
      glutamate levels and AChE activity as well as decreases in brain GSH level and
      SOD and CAT activities. In addition, KCN significantly decreased norepinephrine,
      dopamine and serotonin levels in different brain regions which were resolved by
      MECP. From the present results, it can be concluded that the neuroprotective
      effects of MECP against KCN-induced seizures and oxidative stress may be due to
      the inhibition of oxidative stress overproduction and maintenance of antioxidant
      defense mechanisms.

PMID- 24308564
TI  - Treatment sequencing strategy for hepatic epithelioid haemangioendothelioma.
AB  - BACKGROUND: The biology of hepatic epithelial haemangioendothelioma (HEHE) is
      variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary
      owing to the rarity of the disease and frequent misdiagnosis. METHODS: Between
      1989 and 2013, patients retrospectively identified with HEHE from a single
      academic cancer centre were analysed to evaluate clinicopathological factors and
      initial treatment regimens associated with survival. RESULTS: Fifty patients with
      confirmed HEHE had a median follow-up of 51 months (range 1-322). There was no
      difference in 5-year survival between patients presenting with unilateral
      compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P =
      0.1), localized compared with metastatic disease (69% versus 78.3%, respectively;
      P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or
      Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9).
      However, 5-year survival for patients treated with chemotherapy at any point
      during their disease course was decreased compared with those who did not receive
      any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive
      of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9-10.7), P =
      0.02]. CONCLUSIONS: HEHE frequently follows an indolent course, suggesting that
      immediate treatment may not be the optimal strategy. Initial observation to
      assess disease behaviour may better stratify treatment options, reserving surgery
      for those who remain resectable/transplantable. Prospective cooperative trials or
      registries may confirm this strategy.

PMID- 24308565
TI  - Children's views on microneedle use as an alternative to blood sampling for
      patient monitoring.
AB  - OBJECTIVES: To explore children's views on microneedle use for this population,
      particularly as an alternative approach to blood sampling, in monitoring
      applications, and so, examine the acceptability of this approach to children.
      METHODS: Focus groups were conducted with children (aged 10-14 years) in a range
      of schools across Northern Ireland. Convenience sampling was employed, i.e.
      children involved in a university-directed community-outreach project
      (Pharmacists in Schools) were recruited. KEY FINDINGS: A total of 86 children
      participated in 13 focus groups across seven schools in Northern Ireland. A
      widespread disapproval for blood sampling was evident, with pain, blood and
      traditional needle visualisation particularly unpopular aspects. In general,
      microneedles had greater visual acceptability and caused less fear. A patch-based
      design enabled minimal patient awareness of the monitoring procedure, with
      personalised designs, e.g. cartoon themes, favoured. Children's concerns included
      possible allergy and potential inaccuracies with this novel approach; however,
      many had confidence in the judgement of healthcare professionals if deeming this
      technique appropriate. They considered paediatric patient education critical for
      acceptance of this new approach and called for an alternative name, without any
      reference to 'needles'. CONCLUSIONS: The findings presented here support the
      development of blood-free, minimally invasive techniques and provide an initial
      indication of microneedle acceptability in children, particularly for monitoring
      purposes. A proactive response to these unique insights should enable microneedle
      array design to better meet the needs of this end-user group. Further work in
      this area is recommended to ascertain the perspectives of a purposive sample of
      children with chronic conditions who require regular monitoring.

PMID- 24308566
TI  - OGA: an ontological tool of human phenotypes with genetic associations.
AB  - BACKGROUND: The availability of genetic data has increased dramatically in recent
      years. The greatest value of this data is its potential for personalized
      medicine. Many new associations are reported every day from Genome Wide
      Association Studies (GWAS). However, robust, reproducible associations are
      elusive for some complex diseases. Ontologies present a potential way to
      distinguish between spurious associations and those with a potential influence on
      the phenotype. Such an approach would be based on finding associations of the
      same genetic variant with closely related, but distinct, phenotypes. This
      approach can be accomplished with a phenotype ontology that also holds genetic
      association data. RESULTS: Here, we report a structured knowledge application to
      navigate and to facilitate the discovery of relationships between different
      phenotypes and their genetic associations. CONCLUSIONS: OGA allows users to (1)
      find the intersecting set of genes for phenotypes of interest, (2) find empirical
      p values for such observations and (3) OGA outperforms similar applications in
      number of total concepts and genes mapped.

PMID- 24308569
TI  - Receptor-like kinases: key regulators of plant development and defense.

PMID- 24308567
TI  - Effects of requested, forced and denied shift schedule change on work ability and
      health of nurses in Europe -results from the European NEXT-Study.
AB  - BACKGROUND: Previous cross-sectional findings from the European Nurses Early Exit
      Study (NEXT) show that nurses who were dissatisfied with their work schedule
      tended to consider leaving the nursing profession. Mediating factors in this
      decision process may be caused by self-perceived poor work ability and/or health.
      The aim of this paper is to investigate changes in work ability and general
      health among nurses in relation to requested, forced and denied change of shift
      schedule. METHODS: Longitudinal data from the NEXT Study was used. In total
      11,102 nurses from Belgium, Germany, Finland, the Netherlands, Poland, Slovakia,
      France and Italy completed both the 'basic questionnaire' (t1) and the '12 month
      follow-up questionnaire' (t2). To examine the time-effect (repeated measures) and
      the group-effect of five defined groups of nurses on the Work Ability Index (WAI)
      and general health (SF36), an adjusted 2-way analysis of covariance (ANCOVA) was
      performed. RESULTS: The nurses who wanted to, but could not change their shifts
      during the 12 month follow-up had the lowest initial and follow-up scores for WAI
      (t1: 37.6, t2: 36.6, p <0.001), lowest general health (t1: 63.9, t2: 59.2, p
      <0.001) and showed the highest decrease in both outcomes. Shift pattern change in
      line with the nurses' wishes was associated with improved work ability and to a
      lesser comparatively low extent with increased decline in health scores. A forced
      change of shift against the nurses' will was significantly associated with a
      deteriorating work ability and health. CONCLUSIONS: The findings would suggest
      that nurses' desire to change their shift patterns may be an indicator for
      perceived low work ability and/or low health. The results also indicate that
      fulfilling nurses' wishes with respect to their shift work pattern may improve
      their personal resources such as work ability and - to somewhat lesser extent -
      health. Disregarding nurses' preferences, however, bears the risk for further
      resource deterioration. The findings imply that shift schedule organization may
      constitute a valuable preventive tool to promote nurses' work ability and - to
      lesser extent - their perceived health, not least in aging nursing work forces.

PMID- 24308570
TI  - BAK1 directly regulates brassinosteroid perception and BRI1 activation.
AB  - Plants utilize plasma membrane-localized receptor-like kinases (RLKs) to sense
      extracellular signals to coordinate growth, development, and innate immune
      responses. BAK1 regulates multiple signaling pathways acting as a co-receptor of
      several distinct ligand-binding RLKs. It has been debated whether BAK1 serves as
      an essential regulatory component or only a signal amplifier without pathway
      specificity. This issue has been clarified recently. Genetic and structural
      analyses indicated that BAK1 and its homologs play indispensible roles in
      mediating brassinosteroid (BR) signaling pathway by directly perceiving the
      ligand BR and activating the receptor of BR, BRI1. The mechanism revealed by
      these studies now serves as a paradigm for how a pair of RLKs can function
      together in ligand binding and subsequent initiation of signaling. [Figure: see
      text] Jia Li (Corresponding author). 

PMID- 24308571
TI  - Receptor-like kinases in plant innate immunity.
AB  - Plants employ a highly effective surveillance system to detect potential
      pathogens, which is critical for the success of land plants in an environment
      surrounded by numerous microbes. Recent efforts have led to the identification of
      a number of immune receptors and components of immune receptor complexes. It is
      now clear that receptor-like kinases (RLKs) and receptor-like proteins (RLPs) are
      key pattern-recognition receptors (PRRs) for microbe- and plant-derived molecular
      patterns that are associated with pathogen invasion. RLKs and RLPs involved in
      immune signaling belong to large gene families in plants and have undergone
      lineage specific expansion. Molecular evolution and population studies on
      phytopathogenic molecular signatures and their receptors have provided crucial
      insight into the co-evolution between plants and pathogens. [Figure: see text]
      Jian-Min Zhou (Corresponding author). 

PMID- 24308572
TI  - Reciprocal effects of treatment-induced increases in exercise and improved
      eating, and their psychosocial correlates, in obese adults seeking weight loss: a
      field-based trial.
AB  - BACKGROUND: A better understanding of interrelations of exercise and improved
      eating, and their psychosocial correlates of self-efficacy, mood, and self
      regulation, may be useful for the architecture of improved weight loss
      treatments. Theory-based research within field settings, with samples possessing
      high probabilities of health risks, might enable rapid application of useful
      findings. METHODS: Adult volunteers with severe obesity (body mass index [BMI] 35
      50 kg/m2; age = 43.0 +/- 9.5 y; 83% female) were randomly assigned to six monthly
      cognitive-behavioral exercise support sessions paired with either group-based
      nutrition education (n = 145) or cognitive behavioral methods applied to improved
      eating (n = 149). After specification of mediation models using a bias-corrected
      bootstrapping procedure, a series of reciprocal effects analyses assessed: a) the
      reciprocal effects of changes in exercise and fruit and vegetable intake,
      resulting from the treatments, b) the reciprocal effects of changes in the three
      psychosocial variables tested (i.e. self-efficacy, mood, and self-regulation) and
      fruit and vegetable change, resulting from change in exercise volume, and c) the
      reciprocal effects of changes in the three psychosocial variables and exercise
      change, resulting from change in fruit and vegetable intake. RESULTS: Mediation
      analyses suggested a reciprocal effect between changes in exercise volume and
      fruit and vegetable intake. After inclusion of psychosocial variables, also found
      were reciprocal effects between change in fruit and vegetable intake and change
      in mood, self-efficacy for controlled eating, and self-regulation for eating; and
      change in exercise volume and change in mood and exercise-related self
      regulation. CONCLUSION: Findings had implications for behavioral weight-loss
      theory and treatment. Specifically, results suggested that treatments should
      focus upon, and leverage, the transfer effects from each of the primary weight
      loss behaviors (exercise and healthy eating) to the other. Findings on
      psychosocial correlates of these behavioral processes may also have practical
      applications.

PMID- 24308573
TI  - Encapsulation of an enzyme cascade within the bacteriophage P22 virus-like
      particle.
AB  - Developing methods for investigating coupled enzyme systems under conditions that
      mimic the cellular environment remains a significant challenge. Here we describe
      a biomimetic approach for constructing densely packed and confined multienzyme
      systems through the co-encapsulation of 2 and 3 enzymes within a virus-like
      particle (VLP) that perform a coupled cascade of reactions, creating a synthetic
      metabolon. Enzymes are efficiently encapsulated in vivo with known
      stoichiometries, and the kinetic parameters of the individual and coupled
      activities are characterized. From the results we develop and validate a
      mathematical model for predicting the expected kinetics for coupled reactions
      under co-localized conditions. 

PMID- 24308575
TI  - Understanding influenza vaccination behaviors: a comprehensive sociocultural
      framework.
AB  - Despite the existence of an effective pharmaceutical means for its prevention
      available now for about 70 years, influenza remains an important contributor to
      morbidity and mortality figures due to respiratory infectious diseases through
      the world. Understanding why people accept or reject being vaccinated in our
      societies may contribute to improve substantially public health interventions in
      this domain by addressing the main reasons that lead individuals and groups to
      neglect immunization. Research into the cognitive and social causes of influenza
      vaccination patterns has developed over the last decades. However, it has yielded
      mostly inconsistent or contradictory results. To make sense of the body of data
      available and to improve future research, the authors argue for the adoption of a
      comprehensive sociocultural understanding of vaccination behavior. This could be
      constructed from existing social stratification models used in social sciences
      and should take into account how culture determines cognition. 

PMID- 24308574
TI  - Height and the risk of gestational diabetes: variations by race/ethnicity.
AB  - AIMS: Gestational diabetes is a common pregnancy complication affecting
      races/ethnicities disproportionally. Adult height, an indicator of both genetic
      and early-life factors, is inconsistently associated with gestational diabetes
      risk. We examined the association and whether it varies by races in a nationally
      representative US cohort. METHODS: Analyses were conducted among 135 861
      pregnancies in the Consortium on Safe Labor, 5567 of which were diagnosed with
      gestational diabetes based on medical records review. Generalized estimating
      equations were used to estimate odds ratios (95% confidence intervals) of
      gestational diabetes, controlling for other risk factors including body weight.
      Additionally, a meta-analysis of 15 761 pregnancies with gestational diabetes and
      205 828 without gestational diabetes was conducted to estimate the pooled mean
      difference in height between those with gestational diabetes and control
      subjects. RESULTS: Height was inversely associated with gestational diabetes risk
      across races/ethnicities, with the strongest association among Asians (P for
      interaction < 0.01). Comparing extreme quartiles (> 168 vs. < 157 cm), adjusted
      odds ratios (95% confidence intervals) were 0.18 (0.09-0.36) for Asians/Pacific
      Islanders, 0.33 (0.29-0.38) for non-Hispanic white women, 0.39 (0.31-0.51) for
      Hispanics and 0.59 (0.47-0.75) for non-Hispanic black women. Meta-analysis found
      women with gestational diabetes to be significantly shorter than others.
      CONCLUSIONS: Taller women are at lower risk of developing gestational diabetes,
      with the magnitude of association varying significantly across races/ethnicities.

PMID- 24308576
TI  - Novel approaches in polyepitope T-cell vaccine development against HIV-1.
AB  - RV144 clinical trial was modestly effective in preventing HIV infection. New
      alternative approaches are needed to design improved HIV-1 vaccines and their
      delivery strategies. One of these approaches is construction of synthetic
      polyepitope HIV-1 immunogen using protective T- and B-cell epitopes that can
      induce broadly neutralizing antibodies and responses of cytotoxic (CD8(+) CTL)
      and helpers (CD4(+) Th) T-lymphocytes. This approach seems to be promising for
      designing of new generation of vaccines against HIV-1, enables in theory to cope
      with HIV-1 antigenic variability, focuses immune responses on protective
      determinants and enables to exclude from the vaccine compound that can induce
      autoantibodies or antibodies enhancing HIV-1 infectivity. Herein, the authors
      will focus on construction and rational design of polyepitope T-cell HIV-1
      immunogens and their delivery, including: advantages and disadvantages of
      existing T-cell epitope prediction methods; features of organization of
      polyepitope immunogens, which can generate high-level CD8(+) and CD4(+) T
      lymphocyte responses; the strategies to optimize efficient processing,
      presentation and immunogenicity of polyepitope constructs; original software to
      design polyepitope immunogens; and delivery vectors as well as mucosal strategies
      of vaccination. This new knowledge may bring us a one step closer to developing
      an effective T-cell vaccine against HIV-1, other chronic viral infections and
      cancer. 

PMID- 24308577
TI  - Rotavirus vaccination in Brazil: effectiveness and health impact seven years post
      introduction.
AB  - Before vaccine introduction in Brazil, rotavirus caused approximately 650,000
      outpatient visits, 92,000 hospitalizations and 850 deaths annually among children
      aged <5 years. Brazil was one of the first countries to introduce rotavirus
      vaccination into the National Immunisation Program (NIP), in 2006, but estimated
      coverage (87.1%) for 2011 remained lower if compared with other routine
      immunizations (95%). Case-control studies reached effectiveness rates as high as
      85%. Observational studies showed a significant reduction in gastroenteritis
      related hospitalizations and deaths among children aged <1 year, at rates as high
      as 48 and 54%, respectively. There was a significant increase in the relative
      prevalence of G2P[4] genotype after vaccine introduction, reaching 100% of
      strains in some settings. A small increase in intussusception incidence was seen
      within 1 week following the second vaccine dose, but benefits far outweigh any
      potential risk. This article provides an in-depth review of postlicensure studies
      conducted in Brazil 7-year postintroduction. 

PMID- 24308578
TI  - Pneumococcal immunization in immunocompromised hosts: where do we stand?
AB  - Immunocompromised patients are all at risk of invasive pneumococcal disease, of
      different degrees and timings. However, considerable progress in pneumococcal
      immunization over the last 30 years should benefit these patients. The 23-valent
      polysaccharide vaccine has been widely evaluated in these populations, but due to
      its low immunogenicity, its efficacy is sub-optimal, or even low. The principle
      of the conjugate vaccine is that, through the protein conjugation with the
      polysaccharide, the vaccine becomes more immunogenic, T-cell dependent, and thus
      providing a better early response and a boost effect. The 7-valent conjugate
      vaccine has been the first one to be evaluated in different immunocompromised
      populations. We review here the efficacy and safety of the different
      antipneumococcal vaccines in cancer, transplant and HIV-positive patients and
      propose a critical appraisal of the current guidelines. 

PMID- 24308579
TI  - Recent progress concerning CpG DNA and its use as a vaccine adjuvant.
AB  - CpG Oligonucleotides (ODN) are immunomodulatory synthetic oligonucleotides
      designed to specifically agonize Toll-like receptor 9. Here, we review recent
      progress in understanding the mechanism of action of CpG ODN and provide an
      overview of human clinical trial results using CpG ODN to improve the vaccines
      for cancer, allergy and infectious disease. 

PMID- 24308580
TI  - Recent progress in peptide vaccination in cancer with a focus on non-small-cell
      lung cancer.
AB  - Active immunotherapy aimed at the stimulation of tumor-specific T cells has
      established itself within the clinic as a therapeutic option to treat cancer. One
      strategy is the use of so-called peptides that mimic genuine T-cell epitopes as
      vaccines to activate tumor-specific T cells. In various clinical trials,
      different types of vaccines, adjuvants and other immunomodulatory compounds were
      evaluated in patients with different types of tumors. Here, we review the trials
      published in the last 3 years focusing on the T-cell response, the effect of
      immunomodulation and potential relationships with clinical outcomes. Furthermore,
      we would like to make a case for the development of peptide vaccines aiming to
      treat non-small-cell lung cancer, the most common cause of cancer mortality. 

PMID- 24308581
TI  - National choices related to inactivated poliovirus vaccine, innovation and the
      endgame of global polio eradication.
AB  - Achieving the goal of a world free of poliomyelitis still requires significant
      effort. Although polio immunization represents a mature area, the polio endgame
      will require new tools and strategies, particularly as national and global health
      leaders coordinate the cessation of all three serotypes of oral poliovirus
      vaccine and increasingly adopt inactivated poliovirus vaccine (IPV). Poliovirus
      epidemiology and the global options for managing polioviruses continue to evolve,
      along with our understanding and appreciation of the resources needed and the
      risks that require management. Based on insights from modeling, we offer some
      perspective on the current status of plans and opportunities to achieve and
      maintain a world free of wild polioviruses and to successfully implement oral
      poliovirus vaccine cessation. IPV costs and potential wastage will represent an
      important consideration for national policy makers. Innovations may reduce future
      IPV costs, but the world urgently needs lower-cost IPV options. 

PMID- 24308582
TI  - H7N9: can H7N3 live-attenuated influenza vaccine be used at the early stage of
      the pandemic?
AB  - As of October 2013, H7N9 avian influenza viruses caused 137 human cases with 45
      fatalities. Recent studies revealed that only minor adaptive changes are required
      for H7N9 viruses to become pandemic. Vaccination is a primary measure to protect
      population from severe disease and reduce the impact of epidemics and pandemics
      on public health. Several H7N9 candidate vaccine viruses have been generated and
      are now undergoing preclinical and clinical testings, which will take several
      months. Meanwhile, there are several vaccine candidates with H7 hemagglutinin,
      which can be used to prime the immune system for a robust immune response to
      booster vaccination with H7N9 vaccine, with perspectives of a substantial dose
      sparing. H7N3 live-attenuated influenza vaccine besides being attractive priming
      vaccine in prime-boost strategies, has a potential to protect against H7N9 virus,
      as was demonstrated by immune epitope analysis and by the detection of cross
      reactive antibodies in serum samples of volunteers. 

PMID- 24308584
TI  - Comorbid risk, respondent characteristics and likelihood of pneumococcal
      vaccination versus no vaccination among older adults in Brazil.
AB  - This study investigated predictors of pneumococcal polysaccharide vaccine (PPV)
      use among older adults in Brazil. Respondents aged >=50 from 2011 National Health
      and Wellness Survey in Brazil who had ever (vs never) received PPV were compared
      on comorbid risk, sociodemographics and vaccination behaviors. Logistic
      regression and decision tree analyses predicted PPV receipt as a function of the
      measures. Among 3195 respondents, 8.7% reported ever receiving PPV (10.4% among
      those at risk). Adjusting for covariates, adults classified as high or moderate
      risk had significantly greater odds of pneumococcal vaccination (odds ratios
      [ORs]: 2.42 or 1.36, respectively), as were those who received flu vaccinations
      (OR: 2.21) or were parents/guardians of a vaccinated child (OR: 6.48). In Brazil,
      child vaccination appears to be the dominant predictor of adult PPV uptake,
      followed by influenza vaccination. Higher disease risk was a significant
      predictor, but most older at-risk adults (89.6%) did not receive PPV. 

PMID- 24308583
TI  - Is administration of the HPV vaccine during pregnancy feasible in the future?
AB  - Despite the strong evidence supporting the efficacy of the HPV vaccine, the
      uptake rate remains low. One reason for this is that young females do not
      interact frequently with the healthcare system. In fact, pregnancy is often the
      first time young women experience multiple scheduled visits to a health provider.
      We review the data regarding safety of administering the HPV vaccine during
      pregnancy and consider the possibility of incorporating vaccination into prenatal
      care. Although the optimal time for vaccination is prior to sexual debut, this
      does not always occur, and as such, a broader approach to HPV vaccination may be
      necessary. Increasing the vaccine uptake rate among young women who did not
      initiate or complete the series earlier may significantly contribute to the
      decline in HPV-associated diseases. 

PMID- 24308585
TI  - Application of wheat germ cell-free protein expression system for novel malaria
      vaccine candidate discovery.
AB  - Malaria causes about 216 million clinical cases and 0.7 million deaths annually.
      One promising route to address malaria is vaccination. However, so far, not even
      a single licensed malaria vaccine has been developed. Even the effectiveness of
      RTS,S, the world's most advanced malaria vaccine candidate (MVC) in clinical
      trials, is less than 50% efficacy against the disease. This backdrop indicates
      that the search for a truly effective vaccine is far from over and galvanizes us
      to expand the arsenal of promising MVC antigens to include in a next generation
      subunit vaccine. In our previous proof of principle studies, we have found that
      the wheat germ cell-free protein synthesis system (WGCFS) is one of the optimal
      tools for synthesis of quality malaria proteins and hence the identification of
      novel MVCs. This review summarizes the initial progresses so far made regarding
      the identification of novel MVCs using WGCFS. 

PMID- 24308587
TI  - Au/TiO2 superstructure-based plasmonic photocatalysts exhibiting efficient charge
      separation and unprecedented activity.
AB  - Plasmonic photocatalysts were successfully synthesized by the modification of
      TiO2 mesocrystals with Au nanoparticles (NPs) by a simple impregnation method.
      The Au NP sensitizers show a strong photoelectrochemical response in the visible
      light region (400-800 nm) due to their surface plasmon resonance (SPR). The
      diffuse reflectance spectroscopy measurements on a wide range of time scales
      (from picoseconds to minutes) demonstrate that a substantial part of electrons,
      injected from the Au NPs to the TiO2 mesocrystals through the SPR excitation,
      directionally migrate from the basal surfaces to the edges of the plate-like
      mesocrystals through the TiO2 nanocrystal networks and are temporally stored
      there for further reactions. This anisotropic electron flow significantly
      retarded the charge recombination of these electrons with the holes in the Au
      NPs, thereby improving the visible-light-photocatalytic activity (for organic
      pollutant degradation) by more than an order of magnitude, as compared to that of
      conventional Au/TiO2 NP systems. 

PMID- 24308586
TI  - Clustered cases of Bordetella pertussis infection cause high levels of IgG
      antibodies against pertussis toxin in adolescents in Gaobeidian city, China.
AB  - SUMMARY In a large serosurvey performed in Gaobeidian city, China, 1032 children
      and adolescents aged 3-18 years were divided into three age groups: 3-6, 7-11,
      and 12-18 years. The geometric mean of IgG antibodies against pertussis toxin
      (anti-PT IgG) varied from 3.47 IU/ml (3-6 years) to 8.71 IU/ml (12-18 years) and
      the seroprevalence (>= 40 IU/ml) varied from 4.48% (7-11 years) to 11.76% (12-18
      years). Infections were clustered in three secondary schools (schools 1-3).
      However, excluding secondary schools 1-3, the IgG PT levels, seroprevalence and
      rates of recent infections (>100 IU/ml) in secondary schools 4-7 (where
      infections were not clustered) were very close to those in the 3-6 and 7-11 years
      age groups. This suggests that the high seroprevalence and anti-PT IgG levels in
      adolescents in Gaobeidian city, China were caused by the clustered cases in
      certain secondary schools. Our results also suggested that pertussis was still
      circulating in China, and the reported incidence might be underestimated.

PMID- 24308588
TI  - An index of daily step count and systemic inflammation predicts clinical outcomes
      in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Identification of persons with chronic obstructive pulmonary disease
      (COPD) at risk for acute exacerbations (AEs) targets them for close monitoring.
      OBJECTIVES: We examined the ability of a novel index combining physical activity
      and systemic inflammation to identify persons at risk for AEs. METHODS: In an
      observational cohort study of 167 persons with COPD, we assessed daily step
      count, a direct measure of physical activity, with the StepWatch Activity Monitor
      and measured plasma C-reactive protein (CRP) and IL-6 levels. AEs and COPD
      related hospitalizations were assessed prospectively over a median of 16 months.
      Predictors of AEs and COPD-related hospitalizations were assessed using negative
      binomial models. MEASUREMENTS AND MAIN RESULTS: Median daily step count was 5,203
      steps (interquartile range, 3,627-7,024). Subjects with daily step count <= 5,203
      and CRP > 3 mg/l had an increased rate of AEs (rate ratio [RR], 2.06; 95%
      confidence interval [CI], 1.30-3.27) and COPD-related hospitalizations (RR, 3.51;
      95% CI, 1.73-7.11) compared with subjects with daily step count > 5,203 and CRP
      <= 3 mg/l, adjusting for FEV1% predicted and prednisone use for AE in the
      previous year. Similarly, subjects with daily step count <= 5,203 and IL-6 > 2
      pg/ml had an increased rate of AEs (RR, 2.04; 95% CI, 1.14-3.63) and COPD-related
      hospitalizations (RR, 4.27; 95% CI, 1.56-11.7) compared with subjects with daily
      step count > 5,203 and IL-6 <= 2 pg/ml. CONCLUSIONS: An index combining daily
      step count and systemic inflammation can predict AEs and COPD-related
      hospitalizations. A validation study in a separate cohort is needed to confirm
      the utility of the proposed index as a clinical tool to risk stratify persons
      with COPD.

PMID- 24308589
TI  - Perception of odor-induced tastes following insular cortex lesion.
AB  - Lesions of the insula can affect olfaction and gustation. Here, we examined the
      effect of insula lesions on taste and taste-like experiences generated via
      smelling (i.e., odor-induced tastes) in patients with focal insula lesions and
      intact olfaction. From a set of 16 patients with lesions to the insula, we found
      7 (6 with right-sided lesions) who performed normally on various olfactory
      measures. These were compared to 42 normal control subjects on tests of gustatory
      and odor-induced taste perception as well as control measures. The patients were
      impaired relative to controls on most gustatory measures. They were also impaired
      on tests of odor-induced taste perception, primarily for stimuli presented on the
      left side. Examining cases individually revealed evidence of a dissociation: two
      patients exhibited no impairment in odor-induced taste perception in spite of
      gustatory deficits. Together, these findings suggest that the insula mediates
      taste recognition, hedonics, and intensity judgments as well as odor-induced
      taste perception. However, the areas responsible for aspects of taste perception
      and those responsible for odor-induced taste do not fully overlap each other and
      they are also independent of olfactory areas. 

PMID- 24308590
TI  - Gastric cancer after mini-gastric bypass surgery: a case report and literature
      review.
AB  - Gastric cancer in the stomach after Roux-en-Y gastric bypass or mini-gastric
      bypass is rare, but a few cases have been reported since 1991, when the first
      case emerged. According to the literature, the interval between bypass surgery
      and the diagnosis of cancer ranged from 1 to 22 years. Given the difficulty of
      monitoring a bypassed stomach, the potential for gastric cancer must be
      considered, especially in countries with high incidence of this cancer. The
      literature reported the first case in the Asia-Pacific region - a woman developed
      advanced gastric cancer in her stomach 9 years after laparoscopic mini-gastric
      bypass for morbid obesity.

PMID- 24308591
TI  - Single-incision laparoscopic and endoscopic cooperative surgery for
      gastrointestinal stromal tumor arising from the duodenum.
AB  - We report a case involving a minimally invasive single-incision laparoscopic and
      endoscopic cooperative local excision of a duodenal gastrointestinal stromal
      tumor. A 59-year-old man presented with a 35-mm lesion located in the second
      portion of the duodenum. A local resection was performed via single-incision
      laparoscopic and endoscopic cooperative surgery. Intraluminal endoscopic
      dissection of the duodenal mucosa and submucosa was performed circumferentially
      around the tumor. The resection was then completed by laparoscopic dissection of
      the seromuscular layer around the tumor. The tumor was retrieved
      laparoscopically. After confirming that the resection achieved clear surgical
      margins, we closed the duodenal wall with a laparoscopic stapling device. There
      were no postoperative complications, including stenosis. Single-incision
      laparoscopic and endoscopic cooperative surgery can be safely and effectively
      performed for a duodenal submucosal tumor. 

PMID- 24308592
TI  - Retrograde colon intussusception in an adult due to adenoma: treatment by
      combined laparoscopic and endoscopic approach.
AB  - This report describes the case of a young patient who underwent laparoscopic
      surgery to reduce for a retrograde intussusception of the sigmoid-descending
      colon caused by adenoma of the sigmoid colon. A 36-year-old woman visited our
      hospital, complaining primarily of vomiting and abdominal pain. Abdominal CT scan
      showed the typical finding of intussusception. An emergency colonoscopy revealed
      that the invaginated colon with a polypoid mass was protruding into the
      descending colon. A gastrografin enema showed the invaginated bowel segment at
      the descending colon. We performed endoscopic polypectomy and then hand-assisted
      laparoscopic reduction. The pathological finding showed tubular adenoma.
      Laparoscopy is a diagnostic or therapeutic tool for selected cases of adult
      intussusception. Benign tumor is one of the causes of intussusception in adults
      and a good indication for laparoscopic surgery. 

PMID- 24308593
TI  - Laparoscopic total pelvic exenteration with en bloc lateral lymph node dissection
      after neoadjuvant chemoradiotherapy for advanced primary rectal cancer.
AB  - Total pelvic exenteration (TPE) may be the only procedure that can cure T4 rectal
      cancer that directly invades the urinary bladder or prostate. Here, we describe
      our experience of laparoscopic TPE with en bloc lateral lymph node dissection for
      advanced primary rectal cancer. A 62-year-old man diagnosed with advanced lower
      rectal cancer (T4bN0M0) underwent laparoscopic TPE with en bloc lateral lymph
      node dissection after neoadjuvant chemoradiotherapy. Ligation of the dorsal vein
      complex was performed under direct visualization through the perineal approach,
      and the large perineal defect was reconstructed using bilateral V-Y advancement
      of the gluteus maximus musculocutaneous flaps. The ileal conduit was constructed
      extracorporeally through an extended umbilical port that was extended to 4 cm.
      The total operative time was 831 min and estimated blood loss was 600 mL.
      Laparoscopic TPE appears to be safe and feasible in selected patients.

PMID- 24308594
TI  - Pure laparoscopic posterior sectionectomy for liver metastasis resulting from
      choroidal malignant melanoma: a case report.
AB  - Liver metastases resulting from primary choroidal malignant melanomas occur
      frequently and have a poor prognosis. As a result of advancements in
      multidisciplinary approaches, life expectancy can be increased when R0 resection
      is possible. Herein we report the surgical outcomes of pure laparoscopic
      posterior sectionectomy (PLPS) in a patient with a solitary liver metastasis
      resulting from choroidal malignant melanoma. The subject was a 46-year-old
      Japanese man who had received radiotherapy for primary right choroidal malignant
      melanoma 2 years before presenting at our hospital; he subsequently underwent
      ophthalmectomy as a result of the relapse. During follow-up, CT revealed a
      metastatic lesion in the liver S7, and interventional treatments were performed
      sequentially. The lesion still showed a tendency to enlarge, so we performed
      PLPS. On postoperative day 7, the patient was discharged from the hospital, and
      he started to receive adjuvant chemotherapy 2 weeks after PLPS. Although PLPS is
      deemed to be difficult for lesions in the upper part or posterior segment of the
      liver, we performed this modality safely. 

PMID- 24308595
TI  - Salvage treatment of laparoscopic cholecystectomy-associated bile duct stenosis
      combining laparoscopic and endoscopic procedures: a case report.
AB  - The incidence of laparoscopic cholecystectomy (LC)-associated bile duct injury
      has reached a steady state despite learning curve effect. Herein we report the
      case of a 74-year-old Japanese man who suffered from bile duct stenosis and
      stones after LC. The stenosis was due to stricture caused by surgical clips used
      inappropriately during LC. We planned a salvage treatment combining laparoscopic
      and endoscopic approaches. At laparoscopic observation, the clips had already
      invaded the right side of the bile duct; minimal absorbable suture was performed
      after all the clips were removed. The bile duct stenosis was then endoscopically
      dilated and the biliary stones were successfully removed. For the recurrent
      biliary stenosis after discharge, endoscopic balloon dilation was performed and
      multiple plastic stent tubes were placed. The stent tubes were removed 4 months
      later, and the patient has had no symptoms for 1 year. A combined laparoscopic
      and endoscopic approach was useful for the salvage treatment of LC-associated
      bile duct stenosis.

PMID- 24308596
TI  - Successful laparoscopic management of a primary omental pregnancy: case report
      and review of literature.
AB  - A 32-year-old gravid 1, parity 0 woman was referred to our hospital with
      suspicion of ectopic pregnancy 31 days after her previous menstrual period. She
      had a 5-month history of secondary infertility reported increasing lower
      abdominal pain. Her serum human chronic gonadotropin level was 8160 mIU/mL. Her
      medical history was significant for a myomectomy and an enucleation of left
      ovarian cyst. On suspicion of an ectopic pregnancy, laparoscopic exploration was
      performed. Dense pelvic adhesion was seen. After dissection of the adhesion, we
      could not find the blastocyst in her pelvis. Early pregnancy tissue implanted in
      the omentum was identified and was excised laparoscopically. The postoperative
      course was uneventful. When no ectopia is found in the fallopian tubes during
      laparoscopy or laparotomy for ectopic pregnancy, all peritoneal surfaces and the
      omentum must be carefully inspected during surgery.

PMID- 24308597
TI  - Thymic metastasis of breast cancer 22 years after surgery: a case report.
AB  - We report a rare case of thymic metastasis of breast cancer. A 68-year-old woman,
      who had undergone surgery for cancer in her right breast and had been free of
      recurrence for 22 years, was noted to have an abnormal shadow on a chest X-ray at
      a regular medical checkup. Further workup, including chest CT, revealed a 22 * 18
      mm mass in the anterior mediastinum. Fluorine-18-fluorodeoxyglucose-PET showed
      increased fluorine-18-fluorodeoxyglucose uptake that was highly suggestive of
      thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the
      pericardium, which was also resected. A small nodule was found in the right lung,
      and it was also resected. The intraoperative frozen-section diagnosis was breast
      cancer metastasis to the thymus and lung. The pathological diagnosis was luminal
      A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor
      positive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, the
      patient was treated with an aromatase inhibitor. As of August 2013, she has been
      free of recurrence for more than 36 months. It is extremely rare for breast
      cancer to metastasize to the thymus more than 20 years after surgery.

PMID- 24308598
TI  - Retrocolic roux-en-Y anastomosis for total laparoscopic distal gastrectomy: fix
      the-remnant-first technique.
AB  - INTRODUCTION: Herein we report our retrocolic Roux-en-Y anastomosis for
      laparoscopic distal gastrectomy and its feasibility. MATERIALS AND SURGICAL
      TECHNIQUE: After laparoscopic distal gastrectomy with lymphadenectomy, the
      gastric remnant was fixed through the mesentery of the transverse colon. The
      gastrojejunostomy was performed with linear stapling devices at an angle that
      allowed for easy application. The jejunojejunostomy was also performed with
      linear stapling devices. All spaces between the mesentery were hand-sewn closed.
      This procedure was performed laparoscopically without additional incisions in all
      34 patients. The median operative time was 365 min and the median blood loss was
      50 mL. All patients started liquid intake the day after gastrectomy. There were
      three cases of Grade 1 complications and one Grade 2 complication per the Clavien
      Dindo Classification. Patients' weights after surgery were stable at the 36-month
      follow-up. DISCUSSION: The advantages of Roux-en-Y reconstruction have been
      reported to include less frequent anastomotic leakage, less gastritis and less
      bile reflux over the long term. The retrocolic reconstructions were performed in
      a manner similar to open surgery but under a laparoscopic view. The mesentery
      closure stitches to prevent internal herniation did not require as many stitches
      as the antecolic route and were easier to place. Our anastomosis for laparoscopic
      distal gastrectomy showed acceptable short-term results, with patients
      maintaining up to 91.0% of their preoperative weight and nutritional input. By
      fixing the remnant stomach to the mesentery of the transverse colon before the
      anastomosis, we easily completed the retrocolic Roux-en-Y anastomosis under
      laparoscopic view.

PMID- 24308599
TI  - Complete laparoscopic surgery for early colorectal cancer after endoscopic
      resection.
AB  - INTRODUCTION: Laparoscopic-assisted colorectal surgery requires a mini-laparotomy
      to extract the specimen and insert the anvil head of the circular stapler into
      the proximal colon. However, such a mini-laparotomy occasionally causes local
      pain and surgical-site infection. To avoid mini-laparotomy, we invented a new
      laparoscopic technique, complete laparoscopic surgery for colorectal cancer.
      MATERIALS AND SURGICAL TECHNIQUE: Sigmoid colon or rectal cancer patients who had
      undergone colonoscopic excision for T1 cancer and subsequently required bowel
      resection due to unfavorable histology were recruited. This new procedure used
      both the double stapling technique and the rectal-prolapsing technique, where the
      anvil was transanally inserted into the proximal colon and bowel resection was
      extracorporeally performed after pulling out the colon-rectum via the anus.
      DISCUSSION: This procedure was attempted in 17 patients and successfully achieved
      in 13 patients. Total laparoscopic colorectal surgery has some problems such as
      bacterial contamination or infection, as well as dissemination caused by
      intraluminal exfoliated cancer cells. This procedure is limited to post
      endoscopic resection patients who are suited for reconstruction by double
      stapling technique, and it may be impossible in patients with thick mesentery or
      anal stenosis. Moreover, this method resolves issues of peritoneal contamination
      and dissemination. However, a new protection method for implantation of
      exfoliated cancer cells needs to be established, so that complete laparoscopic
      surgery can be employed in patients with small cancers.

PMID- 24308600
TI  - Percutaneous nephroscopic management of an isolated giant renal hydatid cyst
      guided by single-incision laparoscopy using conventional instruments: the Santosh
      PGI technique.
AB  - INTRODUCTION: Isolated renal hydatid rarely presents, but when it does occur, it
      requires surgical treatment. We report our experience with a novel technique
      involving percutaneous management of a giant renal hydatid cyst with single
      incision laparoscopic assistance. MATERIAL AND SURGICAL TECHNIQUE: First we
      performed retrograde ureteropyelogram, which did not show any communication
      between the cyst and the calyceal. A Veress needle was used for pneumoperitoneum.
      Three conventional laparoscopic trocars used. Under laparoscopic guidance, we
      punctured the cyst. The scolicidal solution used was 10% povidone-iodine. The
      endocyst was removed under vision with grasping forceps through the nephroscope.
      A Portex drain was placed into the cyst cavity. DISCUSSION: Percutaneous
      aspiration and instillation of scolicidal agents followed by re-aspiration have
      been previously reported. This is an attractive procedure because of its
      acceptable success rates and reduced morbidity. In our case, simple aspiration of
      the cyst would not have been successful because the cyst was full of daughter
      cysts. Also, a blind percutaneous puncture of the cyst and dilatation could have
      perforated the colon or the mesocolon, which is often wrapped over the surface of
      such giant cysts thereby making laparoscopic guidance and mobilization of the
      colon imperative. We devised this unique treatment method for this patient
      involving three conventional ports at a single umbilical site. We believe this is
      the first reported case of its kind in the world. Not only this technique is
      minimally invasive, it is also cost-effective, as only conventional laparoscopic
      ports and instruments are used during the procedure.

PMID- 24308602
TI  - Description of aromaticity with the help of vibrational spectroscopy: anthracene
      and phenanthrene.
AB  - A new approach is presented to determine pi-delocalization and the degree of
      aromaticity utilizing measured vibrational frequencies. For this purpose, a
      perturbation approach is used to derive vibrational force constants from
      experimental frequencies and calculated normal mode vectors. The latter are used
      to determine the local counterparts of the vibrational modes. Next, relative bond
      strength orders (RBSO) are obtained from the local stretching force constants,
      which provide reliable descriptors of CC and CH bond strengths. Finally, the RBSO
      values for CC bonds are used to establish a modified harmonic oscillator model
      and an aromatic delocalization index AI, which is split into a bond weakening
      (strengthening) and bond alternation part. In this way, benzene, naphthalene,
      anthracene, and phenanthrene are described with the help of vibrational
      spectroscopy as aromatic systems with a slight tendency of peripheral pi
      delocalization. The 6.8 kcal/mol larger stability of phenanthrene relative to
      anthracene predominantly (84%) results from its higher resonance energy, which is
      a direct consequence of the topology of ring annelation. Previous attempts to
      explain the higher stability of phenanthrene via a maximum electron density path
      between the bay H atoms are misleading in view of the properties of the electron
      density distribution in the bay region. 

PMID- 24308601
TI  - Proanthocyanidin synthesis in Theobroma cacao: genes encoding anthocyanidin
      synthase, anthocyanidin reductase, and leucoanthocyanidin reductase.
AB  - BACKGROUND: The proanthocyanidins (PAs), a subgroup of flavonoids, accumulate to
      levels of approximately 10% total dry weight of cacao seeds. PAs have been
      associated with human health benefits and also play important roles in pest and
      disease defense throughout the plant. RESULTS: To dissect the genetic basis of PA
      biosynthetic pathway in cacao (Theobroma cacao), we have isolated three genes
      encoding key PA synthesis enzymes, anthocyanidin synthase (ANS), anthocyanidin
      reductase (ANR) and leucoanthocyanidin reductase (LAR). We measured the
      expression levels of TcANR, TcANS and TcLAR and PA content in cacao leaves,
      flowers, pod exocarp and seeds. In all tissues examined, all three genes were
      abundantly expressed and well correlated with PA accumulation levels, suggesting
      their active roles in PA synthesis. Overexpression of TcANR in an Arabidopsis ban
      mutant complemented the PA deficient phenotype in seeds and resulted in reduced
      anthocyanidin levels in hypocotyls. Overexpression of TcANS in tobacco resulted
      in increased content of both anthocyanidins and PAs in flower petals.
      Overexpression of TcANS in an Arabidopsis ldox mutant complemented its PA
      deficient phenotype in seeds. Recombinant TcLAR protein converted
      leucoanthocyanidin to catechin in vitro. Transgenic tobacco overexpressing TcLAR
      had decreased amounts of anthocyanidins and increased PAs. Overexpressing TcLAR
      in Arabidopsis ldox mutant also resulted in elevated synthesis of not only
      catechin but also epicatechin. CONCLUSION: Our results confirm the in vivo
      function of cacao ANS and ANR predicted based on sequence homology to previously
      characterized enzymes from other species. In addition, our results provide a
      clear functional analysis of a LAR gene in vivo.

PMID- 24308603
TI  - Laparoendoscopic single-site partial nephrectomy without hilar clamping using a
      microwave tissue coagulator.
AB  - PURPOSE: To report our initial experience and evaluate the possibility of
      nonhilar clamp laparoendoscopic single-site (LESS) partial nephrectomy by using a
      microwave tissue coagulator. PATIENTS AND METHODS: From December 2010 to May
      2012, all patients with an exophytic, solitary, enhancing small (<=4.0 cm) renal
      mass were chosen to receive the study treatment. A multichannel port provided
      both a retroperitoneal and transperitoneal approach. A rigid, articulating
      apparatus was used to perform dissection, exposure of tumor, tissue coagulation,
      and resection without hilar clamping. Pathologic and hematologic data, subjective
      evaluation of pain, and scar appearance were analyzed. RESULTS: Nonhilar clamp
      LESS partial nephrectomy by using a microwave tissue coagulator was performed in
      seven patients (mean operative time, 208 min; mean blood loss, 39 mL; mean renal
      mass size, 1.7 cm); one procedure with uncontrolled bleeding needed to be
      converted to conventional laparoscopic partial nephrectomy. No transfusion was
      necessary. Pathologic investigation demonstrated six renal-cell carcinomas and
      one oncocytoma. The hemoglobin level decreased by a mean of 1.1 g/dL. Patients
      did not complain about pain, and they had great satisfaction with the results.
      The mean duration of hospital stay was 13.8 days. CONCLUSIONS: LESS partial
      nephrectomy without hilar clamping by using a microwave tissue coagulator is
      possible for renal masses, confers postoperative outcomes comparable to the
      standard counterpart, and assures patient satisfaction. By use of a microwave
      tissue coagulator, additional trocars were not necessary, and LESS partial
      nephrectomy could be accomplished through a single port, which reduced invasion
      and increased the cosmetic satisfaction of the patients.

PMID- 24308604
TI  - A direct-infusion- and HPLC-ESI-Orbitrap-MS approach for the characterization of
      intact PEGylated proteins.
AB  - The characterization of proteins modified with poly(ethylene glycol) (PEG), such
      as recombinant human granulocyte-colony stimulating factor (PEGylated rhG-CSF or
      pegfilgrastim), by electrospray ionization-mass spectrometry (ESI-MS) constitutes
      a challenge due to the overlapping protein charge state pattern and PEG
      polydispersity. In order to minimize spectral overlaps, charge reduction by means
      of the addition of amine was applied. Method development for direct-infusion
      measurements, carried out on an ESI-time-of-flight (ESI-TOF) instrument,
      demonstrated the potential of triethylamine (TEA) for shifting the charge state
      pattern toward lower-charged species and of formic acid (FA) for causing higher
      charging. After successful method transfer to the LTQ Orbitrap XL instrument,
      isotopically resolved mass spectra could be acquired. With a median mass accuracy
      of 1.26 ppm, a number-average monoisotopic molecular mass of 40074.64 Da was
      determined for pegfilgrastim. The direct comparison of three Orbitrap mass
      spectrometers, namely the LTQ Orbitrap XL, the Exactive, and the Q Exactive,
      demonstrated that online interfacing to high performance liquid chromatography
      (HPLC) was only feasible with the Q Exactive, which offers adequate spectral
      quality on a time scale compatible with chromatographic separation (i.e., 0.2 min
      acquisition time per chromatographic peak). Finally, the applicability of both
      direct-infusion Orbitrap MS and HPLC interfaced to Orbitrap MS was demonstrated
      for the detection of methionine oxidation in pegfilgrastim. Singly, doubly, and
      triply oxidized species were readily resolved in the chromatogram, while their
      oxidation status was easily determined from the mass shifts observed in the
      deconvoluted mass spectra. 

PMID- 24308606
TI  - Identification and characterization of novel and differentially expressed
      microRNAs in peripheral blood from healthy and mastitis Holstein cattle by deep
      sequencing.
AB  - MicroRNA (miRNA) mediates post-transcriptional gene regulation and plays an
      important role in regulating the development of immune cells and in modulating
      innate and adaptive immune responses in mammals, including cattle. In the present
      study, we identified novel and differentially expressed miRNAs in peripheral
      blood from healthy and mastitis Holstein cattle by Solexa sequencing and
      bioinformatics. In total, 608 precursor hairpins (pre-miRNAs) encoding for 753
      mature miRNAs were detected. Statistically, 173 unique miRNAs (of 753, 22.98%)
      were identified that had significant differential expression between healthy and
      mastitis Holstein cattle (P < 0.001). Most differentially expressed miRNAs (118
      of 173, 68.21%) belonged to the chemokine signaling pathway involved in the
      immune responses. This study expands the number of miRNAs known to be expressed
      in cattle. The patterns of miRNAs expression differed significantly between the
      peripheral blood from healthy and mastitis Holstein cattle, which provide
      important information on mastitis in miRNAs expression. Diverse miRNAs may play
      an important role in the treatment of mastitis in Holstein cattle. 

PMID- 24308605
TI  - Margin status after laparoscopic resection of colorectal liver metastases: does a
      narrow resection margin have an influence on survival and local recurrence?
AB  - OBJECTIVES: Recent studies of margin-related recurrence have raised questions on
      the necessity of ensuring wide resection margins in the resection of colorectal
      liver metastases. The aim of the current study was to determine whether resection
      margins of 10 mm provide a survival benefit over narrower resection margins.
      METHODS: A total of 425 laparoscopic liver resections were carried out in 351
      procedures performed in 317 patients between August 1998 and April 2012. Primary
      laparoscopic liver resections for colorectal metastases were included in the
      study. Two-stage resections, procedures accompanied by concomitant liver
      ablations and one case of perioperative mortality were excluded. A total of 155
      eligible patients were classified into four groups according to resection margin
      width: Group 1, margins of < 1 mm [n = 33, including 17 patients with positive
      margins (Group 1a)]; Group 2, margins of 1 mm to < 3 mm (n = 31); Group 3,
      margins of >= 3 mm to <10 mm (n = 55), and Group 4, margins of >= 10 mm (n = 36).
      Perioperative and survival data were compared across the groups. Median follow-up
      was 31 months (range: 2-136 months). RESULTS: Perioperative outcomes were similar
      in all groups. Unfavourable intraoperative incidents occurred in 9.7% of
      procedures (including 3.2% of conversions). Postoperative complications developed
      in 11.0% of patients. Recurrence in the resection bed developed in three (1.9%)
      patients, including two (6.1%) patients in Group 1. Rates of actuarial 5-year
      overall, disease-free and recurrence-free survival were 49%, 41% and 33%,
      respectively. Median survival was 65 months. Margin status had no significant
      impact on patient survival. The Basingstoke Predictive Index (BPI) generally
      underestimated survival. This underestimation was especially marked in Group 1
      when postoperative BPI was applied. CONCLUSIONS: Patients with margins of <1 mm
      achieved survival comparable with that in patients with margins of >= 10 mm. When
      modern surgical equipment that generates an additional coagulation zone is
      applied, the association between resection margin and survival may not be
      apparent. Further studies in this field are required. Postoperative BPI, which
      includes margin status among the core factors predicting postoperative survival,
      seems to be less precise than preoperative BPI.

PMID- 24308607
TI  - dsRNA uptake and persistence account for tissue-dependent susceptibility to RNA
      interference in the migratory locust, Locusta migratoria.
AB  - RNA interference (RNAi) by introducing double-stranded RNA (dsRNA) is a powerful
      approach to the analysis of gene function in insects; however, RNAi responses
      vary dramatically in different insect species and tissues, and the underlying
      mechanisms remain poorly understood. The migratory locust, a destructive insect
      pest and a hemimetabolic insect with panoistic ovaries, is considered to be a
      highly susceptible species to RNAi via dsRNA injection, but its ovary appears to
      be completely insensitive. In the present study, we showed that dsRNA persisted
      only briefly in locust haemolymph. The ovariole sheath was permeable to dsRNA,
      but injected dsRNA was not present in the follicle cells and oocytes. The lack of
      dsRNA uptake into the follicle cells and oocytes is likely to be the primary
      factor that contributes to the ineffective RNAi response in locust ovaries. These
      observations provide insights into tissue-dependent variability of RNAi and help
      in achieving successful gene silencing in insensitive tissues. 

PMID- 24308608
TI  - Effects of 4-nonylphenol and bisphenol A on stimulation of cell growth via
      disruption of the transforming growth factor-beta signaling pathway in ovarian
      cancer models.
AB  - Transforming growth factor beta (TGF-beta) signaling pathway is a major pathway
      in cellular processes such as cell growth, apoptosis, and cellular homeostasis.
      The signaling pathway activated by 17beta-estadiol (E2) appeared to inhibit the
      TGF-beta signaling pathway by cross-talk with the TGF-beta components in estrogen
      receptor (ER) positive cells. In this study, we examined the inhibitory effects
      of endocrine disrupting chemicals (EDCs), including 4-nonylphenol (NP), 4
      otylphenol (OP), bisphenol A (BPA), and benzophenon-1 (BP-1), in the TGF-beta
      signaling pathway in BG-1 ovarian cancer cells expressing estrogen receptors
      (ERs). The transcriptional and translational levels of TGF-beta related genes
      were examined by reverse transcription-PCR (RT-PCR), Western blot analysis, and
      xenograft mouse models of ovarian cancer cells. As a result, treatment with NP,
      OP, and BPA induced the expressions of SnoN, a TGF-beta pathway inhibitor, and c
      Fos, a TGF-beta target transcription factor. Treatment with NP, BPA, and BP-1
      resulted in decreased phosphorylation of Smad3, a downstream target of TGF-beta.
      These results indicate that NP and BPA may stimulate the proliferation of BG-1
      cells via inhibition of the TGF-beta signaling pathway. In a xenograft mouse
      model, transplanted BG-1 ovarian cancer cells showed significantly decreased
      phosphorylation of Smad3 and increased expression of SnoN in the ovarian tumor
      masses following treatment with E2, NP, or BPA. In parallel with an in vitro
      model, the expressions of these TGF-beta signaling pathway were similarly
      regulated by NP or BPA in a xenograft mouse model. These results support the fact
      that the existence of an unproven relationship between EDCs/ER-alpha and TGF-beta
      signaling pathway and a further study are required in order to verify more
      profound and distinct mechanism(s) for the disturbance of the TGF-beta signaling
      pathway by diverse EDCs. 

PMID- 24308609
TI  - Trends in mortality and loss to follow-up in HIV care at the Nkongsamba Regional
      hospital, Cameroon.
AB  - BACKGROUND: Access to Human Immunodeficiency Virus (HIV) care has been rolled out
      in Cameroon in the last decade through decentralised delivery of care and timely
      initiation of free antiretroviral drugs. We sought to describe the evolution of
      mortality and loss to follow up (LTFU) and their patient-related determinants at
      an HIV clinic which is facing significant challenges. METHODS: A retrospective
      review of point of care data from HIV patients was conducted in June 2012 at
      Nkongsamba Regional Hospital in Cameroon to establish mortality and LTFU rates.
      Univariable and multivariable Cox regression models were used to screen for
      factors associated with the outcomes. Telephone calls were made to trace patients
      LTFU. RESULTS: Between June 2005 and December 2010, 2388 HIV infected patients
      were admitted. Of these, 1858 were aged 15 and above and were included in our
      analysis. Their median age was 36 years (IQR: 30-44) and they were followed up
      over a total risk period of 3647.3 person-years (pyrs). The overall mortality
      rate was 34.6 deaths per 1000 pyrs (95% CI: 29.0-41.1) while the overall LTFU
      rate was 94.6 per 1000 pyrs (95%CI: 85.1-105.1).The mortality rates steadily rose
      to a peak of 69.6 deaths per 1000 pyrs in 2009 and then fell drastically to 20.6
      per 1000 pyrs in 2010. The LTFU rate increased sharply from 29.7 in 2006 to 138.2
      in 2007 and remained virtually stable until 2010. The factors associated with
      mortality were: being male (aHR=2.25, 95% CI: 1.58-3.19), clinical disease
      progression (aHR=2.0, 95% CI: 1.58-2.53), CD4 count<200 cells/MUl (aHR=3.14, 95%
      CI: 1.27-7.73), haemoglobin level<10 g/dl (aHR=2.50, 95% CI: 1.69-3.69). Major
      factors associated with high LTFU rate were: distance to clinic of over 5 km
      (aHR=1.25, 95% CI: 1.00-1.55), being single, having partners with unknown HIV
      status or taking no treatment and with CD4 count>500 cells/MUl. Two- thirds
      (66.7%) of traced LTFU patients were dead. CONCLUSION: Mortality and LTFU rates
      in our cohort were high but there is evidence that patients' outcomes are
      improving. Interventions to address factors associated with high mortality and
      LTFU should be implemented for optimal results in patient care.

PMID- 24308610
TI  - Predictors of participation in preventive health examinations in Austria.
AB  - BACKGROUND: Preventive health check-ups in Austria are offered free of charge to
      all insured adults (98% of the population) and focus on early detection of
      chronic diseases, primary prevention, and health counseling. The study aims to
      explore predictors of compliance with the recommended interval of preventive
      health check-up performance. METHODS: Source of data was the Austrian Health
      Interview Survey 2006/07 (15,474 subjects). Participation in a preventive health
      examination during the last three years was used as dependent variable. Socio
      demographic and health-related characteristics were used as independent variables
      in a multivariate logistic regression analysis. RESULTS: Results show that 41.6%
      of men and 41.8% of women had attended a preventive health check-up within the
      last three years. In multivariate analysis, subjects >= 40 years, with higher
      education, higher income or born in Austria were significantly more likely to
      attend a preventive health check-up. Furthermore, a chronic disease was
      associated with a higher attendance rate (OR: 1.21; CI: 1.07-1.36 in men; OR:
      1.19; CI: 1.06-1.33 in women). CONCLUSIONS: Attendance rates for health check-ups
      in the general Austrian population are comparatively high but not equally
      distributed among subgroups. Health check-ups must increase among people at a
      young age, with a lower socio-economic status, migration background and in good
      health.

PMID- 24308611
TI  - A good time for change.

PMID- 24308612
TI  - Determining the true burden of general practice patients in the emergency
      department: getting closer.

PMID- 24308613
TI  - Intravenous 0.9% sodium chloride therapy does not reduce length of stay of
      alcohol-intoxicated patients in the emergency department: a randomised controlled
      trial.
AB  - BACKGROUND: I.v. 0.9% sodium chloride (normal saline) is frequently used to treat
      ED patients with acute alcohol intoxication despite the lack of evidence for its
      efficacy. OBJECTIVE: The study aims to compare treatment with i.v. normal saline
      and observation with observation alone in ED patients with acute alcohol
      intoxication. METHODS: A single-blind, randomised, controlled trial was conducted
      to compare a single bolus of 20 mL/kg i.v. normal saline plus observation with
      observation alone. One hundred and forty-four ED patients with uncomplicated
      acute alcohol intoxication were included. The study was conducted in one tertiary
      and one urban ED in Queensland, Australia. Primary outcome was ED length of stay
      (EDLOS). Secondary outcomes were treatment time, breath alcohol levels,
      intoxication symptom score, level of intoxication and associated healthcare
      costs. RESULTS: Both groups were comparable at baseline: blood alcohol content
      (BAC) was similar between treatment and control groups (0.20 % BAC vs 0.19 % BAC,
      P = 0.44) as were initial intoxication symptom scores (22.0 vs 22.3, P = 0.90).
      Both groups had a similar EDLOS (287 min vs 274 min, P = 0.89; difference 13 min
      [95% CI -37-63]) and treatment time (244 min vs 232 min, P = 0.94; difference 12
      min [95% CI -31-55]). Change of breath alcohol levels, intoxication score and
      level of intoxication were not significantly different between the two groups.
      Patients in the treatment group had an additional healthcare cost of A$31.92
      compared with control. CONCLUSIONS: I.v. normal saline therapy added to
      observation alone does not decrease ED length of stay compared with observation
      alone. Intoxication symptom scores and general state of intoxication were similar
      in both groups. The present study suggests that either approach is reasonable,
      but observation alone might be preferred as it is less resource intensive.

PMID- 24308614
TI  - Characteristics of Aboriginal and Torres Strait Islander presentations to three
      Victorian emergency departments.
AB  - OBJECTIVES: Aboriginal and Torres Strait Islander (ATSI) people have significant
      health disparity compared with other Australians. The present study examines the
      characteristics of ATSI patients presenting to three EDs of a single healthcare
      network to determine whether any healthcare disadvantages exist. METHODS: This is
      a retrospective audit of 179,795 presentations to the ED from 1 July 2011 to 30
      June 2012. Measures included socioeconomic status, general practitioner
      nomination, triage category status, primary diagnosis recorded, length of stay
      and the outcome of stay, including numbers leaving before and after medical
      treatment was commenced. RESULTS: ATSI people were found to live in the lower
      socioeconomic regions of the network's catchment area, were more likely to attend
      the ED (135.5 non-ATSI persons presenting per 1000 non-ATSI persons and 210.4
      ATSI persons presenting per 1000 ATSI persons), less likely to nominate a general
      practitioner (73.3 vs 82.1%; OR 0.60, 95% CI 0.51-0.71), more likely to leave
      before (5.5 vs 4.0%; OR 1.40, 95% CI 1.09-1.80) or after treatment had commenced
      (3.2 vs 2.3%; OR 1.43, 95% CI 1.03-1.97), and were more likely to re-attend the
      ED than non-ATSI people (OR 1.24, 95% CI 1.06-1.46). CONCLUSION: ATSI people
      living in Melbourne's south-east have social and health utilisation inequities,
      which might have an impact on their health status.

PMID- 24308615
TI  - Evaluation of a multifaceted intervention on documentation of vital signs at
      triage: a before-and-after study.
AB  - BACKGROUND: Triage systems provide a centralised safety mechanism where all
      patients are assessed for clinical urgency at point of entry to the ED.
      OBJECTIVE: The present study aims to evaluate the effect of a multifaceted
      intervention on triage documentation rates and guideline adherence. METHODS: A
      before-and-after design was used. The intervention involved restructuring the
      computerised interface, regular audit and feedback and education sessions. The
      setting was one adult tertiary referral hospital and major trauma centre located
      in Melbourne, Australia. Participants were triage nurses. Data were collected at
      five time points for a consecutive sample of one month of presentations. RESULTS:
      Over a 15 month period, we sampled 35.8% (24,862/69,395) episodes of triage
      performed by 122 nurses. Documentation rates for all vital signs progressively
      increased from baseline. There were significant increases in the proportion of
      episodes of triage where any vital sign was documented (32.2% vs 82.6%), and
      where pair and triplet combinations of vital signs were recorded in the triage
      field (heart rate and respiratory rate: 17.9% vs 64.6%; heart rate, respiratory
      rate and temperature: 7.0% vs 30.4%). No significant change in guideline
      adherence was observed after the intervention. CONCLUSION: Progressive sustained
      improvements in vital sign documentation were observed over the study period;
      however, no such increases were noted in guideline adherence. To facilitate
      evaluation of guideline adherence, we recommend specific vital sign parameters be
      included in the Australasian Triage Scale Guideline for all levels of urgency.

PMID- 24308616
TI  - Sensitivity and specificity of three-point compression ultrasonography performed
      by emergency physicians for proximal lower extremity deep venous thrombosis.
AB  - OBJECTIVE: The present study aims to quantify the sensitivity and specificity of
      three-point compression ultrasonography for diagnosing proximal lower extremity
      deep venous thrombosis when performed by Australian consultant emergency
      physicians with limited specific training. Secondary aims included quantifying
      rapidity, technical adequacy, predictability of equivocal results and
      relationships between emergency physician experience and proficiency. METHODS:
      This prospective diagnostic study enrolled a convenience sample of adult patients
      presenting to a major ED with suspected lower extremity deep venous thrombosis.
      The index test was abbreviated compression ultrasonography examining three
      points: common femoral, proximal great saphenous and popliteal veins. Emergency
      physicians received specific training. The reference test was full-leg duplex
      ultrasonography in the Radiology Department. RESULTS: A total of 15 emergency
      physicians participated, enrolling 178 subjects. Sensitivity of the index test
      was 77.8% (95% confidence interval: 54.8-91.0%), specificity was 91.4% (95%
      confidence interval: 84.9%-95.3%) and accuracy was 89.6% (95% confidence
      interval: 83.1-94.2%). Median duration of the index test was 10 min 34 s
      (interquartile range: 6 min 31 s) and ED diagnosis occurred significantly before
      Radiology Department diagnosis. The only statistically significant relationship
      between emergency physician experience and proficiency related to rapidity, which
      increased from the 36th scan. Equivocal index tests occurred in 9.2% of
      examinations and emergency physicians predicted equivocal assessments with
      specificity of 86.1% (95% confidence interval: 78.8-91.1%). CONCLUSIONS:
      Abbreviated ultrasonography performed by emergency physicians for proximal lower
      extremity deep venous thrombosis could be valuable. However, more precise
      estimates for sensitivity and greater understanding of relationships between
      emergency physician experience and proficiency are required.

PMID- 24308617
TI  - Design and roll out of standardised approach to paediatric procedural sedation in
      Victorian emergency departments.
AB  - OBJECTIVES: Children sometimes require minor procedures in the ED for which
      sedation is needed. Information from Victorian EDs indicated that processes for
      paediatric procedural sedation were variable, both within and between health
      services. The aims of this project were to improve safety and reduce variation in
      practice with respect to paediatric procedural sedation in EDs by rolling out a
      standardised paediatric sedation programme in Victorian EDs. METHODS: The project
      was managed by a clinical network with support of an expert reference group;
      however, implementation was conducted at the local ED level. The approach was
      multi-modal and grounded in quality and safety theory. It included revision of
      evidence-based training materials, information sheets and risk
      assessment/procedure documentation forms, information on a child and family
      centred approach, a before-and-after clinical governance assessment, and train
      the-trainer activities. The project was evaluated by clinical audit of cases,
      analysis of before-and-after clinical governance assessments, numbers of staff
      completing training and credentialing, and qualitative feedback on the programme
      from ED staff. RESULTS: Fourteen EDs completed the project; 10 metropolitan and
      four regional/rural. Significant shifts in nine key clinical governance items
      were found, including structured training and credentialing, provision of parent
      information sheet, and monitoring of adverse events. The clinical audit showed
      >75% compliance, with seven indicators including recording of weight, fasting
      time and baseline observations, composition of sedation team, and documentation
      that discharge criteria were met. Nine hundred and seventy-one staff were trained
      within the project period. CONCLUSION: This multi-modal implementation strategy
      has achieved clinical practice improvement across organisational boundaries.

PMID- 24308618
TI  - Eighty-seven cases of a nail gun injury to the extremity.
AB  - OBJECTIVES: The aims of this research were to characterise the injury patterns
      associated with nail guns, highlight their potential complications and review
      treatment options. METHODS: A retrospective case series was conducted of all
      patients with a nail gun injury to the upper or lower limb who presented to the
      Princess Alexandra Hospital from 1 January 2007 to 30 July 2012. RESULTS: Young
      men in the work environment were at most risk of sustaining a nail gun injury to
      their non-dominant hand. Out of 87 cases identified, 29% were intra-articular,
      16% had evidence of neurovascular injury, 24% involved bone and 37% had evidence
      of tendon injury. Fifty-eight per cent underwent operative management, 32% were
      treated solely in the ED and 10% were transferred to a private facility. At the
      time of operation, 14% of cases had tendon, joint or neurovascular involvement
      and 20% had retained foreign material. The median length of operation was 17 min
      and no anaesthetic complications were identified. Four (13%) patients had ongoing
      pain, paraesthesia or stiffness at the time of follow up. CONCLUSIONS: The
      present study characterises the injury patterns caused by nail guns. Treatment of
      these injuries should be based on clinical findings; however, the majority of
      cases should undergo surgical treatment. The required operation is a short and
      safe treatment modality that might allow a thorough assessment of the injury,
      removal of embedded material, repair of structural damage and a sterile washout
      to be performed.

PMID- 24308619
TI  - Super selective transcatheter embolisation in the management of acute colonic
      bleeding.

PMID- 24308620
TI  - Direct current cardioversion causing ventricular fibrillation in Wolff-Parkinson
      White syndrome.

PMID- 24308621
TI  - Re: Agreement between arterial and venous pH and pCO2 in patients undergoing non
      invasive ventilation in the emergency department.

PMID- 24308622
TI  - Response to Re: Agreement between arterial and venous pH and pCO2 in patients
      undergoing non-invasive ventilation in the emergency department.

PMID- 24308623
TI  - Changing economy, changing traditions, changing trauma.

PMID- 24308624
TI  - @Toxicology in the Twittersphere: more than just 140 characters....

PMID- 24308626
TI  - Utility of stereoscopic displays for indirect-vision driving and robot
      teleoperation.
AB  - The effectiveness of an active shutter-glasses stereoscopic display (SD) and a
      passive polarised SD was evaluated in a live robot-teleoperation task and a
      simulated indirect-vision driving task in various terrains. Overall, participants
      completed their tasks significantly faster with the SDs in three-dimensional (3D)
      mode than with the SDs in the baseline 2D mode. They also navigated more
      accurately with the SDs in 3D mode. When the effectiveness of the two types of
      SDs was examined separately, results showed that the active shutter-glasses SD
      resulted in faster responses and task completion times than the passive polarised
      SD, though most of the differences failed to reach statistical significance.
      Perceived workload when interacting with the two SD systems did not differ
      significantly between the active versus passive display types or between the 3D
      and 2D modes of operation; however, participants reported more severe discomfort
      after interacting with the passive polarised SD. 

PMID- 24308628
TI  - Travels with carbon-centered radicals. 5'-deoxyadenosine and 5'-deoxyadenosine-5'
      yl in radical enzymology.
AB  - As a graduate student under Professor R. H. Abeles, I began my journey with 5'
      deoxyadenosine, studying the coenzyme B12 (adenosylcobalamin)-dependent
      dioldehydrase (DDH). I proved that suicide inactivation of dioldehydrase by
      glycolaldehyde proceeded with irreversible cleavage of adenosylcobalamin to 5'
      deoxyadenosine. I further showed that suicide inactivation by [2
      (3)H]glycolaldehyde produced 5'-deoxy[(3)H]adenosine, the first demonstration of
      hydrogen transfer to adenosyl-C5' of adenosylcobalamin. The tritium kinetic
      isotope effect (T)k was 15, which correlated well with the measurement (D)k = 12
      for transformation of [1-(2)H]propane-1,2-diol to [2-(2)H]propionaldehyde by DDH.
      After establishing my own research program, I returned to the glycolaldehyde
      inactivation of DDH, showing by EPR that suicide inactivation produced
      glycolaldehyde-2-yl. In retrospect, suicide inactivation involved scission of
      adenosylcobalamin to 5'-deoxyadenosine-5'-yl, which abstracted a hydrogen from
      glycolaldehyde. Captodative-stabilized glycolaldehyde-2-yl could not react
      further, leading to suicide inactivation. In 1986, my colleagues and I took up
      the problem of the mechanism by which lysine 2,3-aminomutase (LAM) catalyzes S
      adenosylmethionine (SAM) and pyridoxal-5'-phosphate (PLP)-dependent
      interconversion of l-lysine and l-beta-lysine. Because the reaction followed the
      pattern of adenosylcobalamin-dependent rearrangements, I postulated that SAM
      might be an evolutionary predecessor to adenosylcobalamin. Testing this
      hypothesis, we traced hydrogen transfer from lysine through the adenosyl-C5' of
      SAM to beta-lysine. Thus, the 5'-deoxyadenosyl of SAM mediated hydrogen transfer
      by LAM exactly as in adenosylcobalamin mediated hydrogen transfer in B12
      dependent isomerizations. The mechanism postulated that SAM cleaves to form 5'
      deoxyadenosine-5'-yl followed by abstraction of C3(H) from PLP-alpha-lysine
      aldimine to form PLP-alpha-lysine-3-yl. PLP-alpha-lysine-3-yl isomerizes to
      pyridoxal-beta-lysine-2-yl, and a hydrogen abstraction from 5'-deoxyadenosine
      regenerates 5'-deoxyadenosine-5'-yl and releases beta-lysine. Of four radicals in
      the postulated mechanism, three have been characterized by EPR spectroscopy as
      kinetically competent intermediates. The analysis of the role of iron allowed
      researchers to elucidate the mechanism by which SAM is cleaved to 5'
      deoxyadenosine-5'-yl. LAM contains one [4Fe-4S] cluster ligated by three cysteine
      residues. As shown by ENDOR spectroscopy and X-ray crystallography, the fourth
      ligand to the cluster is SAM, through the methionyl carboxylate and amino groups.
      Inner sphere electron transfer within the [4Fe-4S](1+)-SAM complex leads to [4Fe
      4S](2+)-Met and 5'-deoxyadenosine-5'-yl. The iron-binding motif in LAM, CxxxCxxC,
      found by other groups in four other SAM-dependent enzymes, is the founding motif
      for the radical SAM superfamily. These enzymes number in the tens of thousands
      and are responsible for highly diverse and chemically difficult transformations
      in the biosphere. Available information supports the hypothesis that this
      superfamily provides the chemical context from which the much more structurally
      complex adenosylcobalamin evolved. 

PMID- 24308627
TI  - Design, synthesis, and biological activity of novel dicoumarol glucagon-like
      peptide 1 conjugates.
AB  - Twelve novel dicoumarol glucagon-like peptide 1 (GLP-1) conjugates were designed,
      synthesized, and tested for biological activity. All derivatives retained
      receptor activation efficacy, and exhibited improved albumin affinity and in
      vitro stability in rat plasma. The in vivo elimination half-lives of 13c and 13 l
      (22.07 and 18.78 h, respectively) were much longer than those of the GLP-1
      receptor agonists exendin-4 (2.82 h) and liraglutide (12.53 h). The prolonged in
      vivo antidiabetic effects of 13c and 13 l on db/db mice were confirmed by the
      hypoglycemic efficacy test and the multiple intraperitoneal glucose tolerance
      test. Importantly, a once daily administration of 13c to db/db mice for 7 weeks
      provided long-term beneficial effects by lowering glycated hemoglobin (HbA1c)
      levels to 5.05%, which was lower than with liraglutide treatment (5.41%). These
      results suggest that 13c is a promising long-lasting GLP-1 mimetic that may be
      suitable for clinical use following further research.

PMID- 24308629
TI  - Population dynamics of Staphylococcus aureus from Northeastern Nigeria in 2007
      and 2012.
AB  - The population structure of Staphylococcus aureus is changing globally but the
      situation regarding dominant clones in sub-Saharan Africa is not clear. We
      therefore assessed changes in the population structure of clinical S. aureus
      isolates obtained in 2007 (n = 75) and 2012 (n = 75) from Northeastern Nigeria. A
      reduction in resistance to penicillin, gentamicin, erythromycin and clindamycin
      was observed in 2012. A decrease of methicillin resistance rates (13.3% to 8.0%)
      was associated with the decline of the ST241 MRSA clone. The proportion of Panton
      Valentine leukocidin (PVL)-positive isolates also decreased from 65.3% to 44%,
      and was linked with the emergence of PVL-negative ST601 clone in 2012. The
      significant decline in antibiotic resistance in the study area is in contrast to
      the worldwide trend of increasing resistance rates.

PMID- 24308630
TI  - Theoretical methodologies for calculation of Judd-Ofelt intensity parameters of
      polyeuropium systems.
AB  - When Judd-Ofelt intensity parameters of polynuclear compounds with asymmetric
      centers are calculated using the current procedure, the results are inconsistent.
      The problem arises from the fact that the experimental intensity parameters
      cannot be determined for each asymmetric polyhedron, and this precludes the
      individual theoretical adjustment. In this study, we then propose three different
      methods for calculation of these parameters of polyeuropium systems. The first,
      named the centroid method, proposes the calculation considering the center of the
      dimeric system as the half distances between the two europium centers. The second
      method, called the overlapped polyhedra method, proposes the calculation
      considering the overlapping of both europium polyhedra, and the last one, the
      individual polyhedron method, proposes the use of theoretical mean values of
      charge factors and polarizabilities associated with each europium-ligand atom
      bond to calculate the intensity parameters. One symmetric polyeuropium system and
      one asymmetric system were assessed by using the three methods. Among the methods
      assessed, the one based on the overlapped polyhedra produced more consistent
      results for the study of both kinds of systems. 

PMID- 24308631
TI  - Recent progress toward development of vaccines against conception.
AB  - Although there are several methods of contraception available, the population
      explosion and unintended pregnancies continue to cause major health issues and
      constrain resources worldwide. A better method of contraception that is
      acceptable in developed as well as developing countries is urgently needed.
      Contraceptive vaccines (CVs) can fulfil most of the properties of an ideal
      contraceptive. The development of CVs is an exciting proposition and has drawn
      significant attention lately. The purpose of this article is to review the
      present status and future perspectives of CVs for human use, and for control of
      farm, feral, stray and domestic animal populations. 

PMID- 24308632
TI  - Saliva composition in three selected groups with normal stimulated salivary flow
      rates, but yet major differences in caries experience and dental erosion.
AB  - OBJECTIVE: It was hypothesized that, by comparing matched subjects with major
      differences in these dental diseases, but yet normal saliva flow rates, it would
      be possible to obtain data on the effect of saliva composition on dental disease
      isolated from the effect of the flow rate. Thus, the aim of the study was to
      compare the major physicochemical characteristics of stimulated whole saliva in
      three groups of 85 subjects, each with normal saliva flow rates and at least 24
      remaining teeth. MATERIALS AND METHODS: A group with very little dental disease
      (healthy), a group with dental erosion (erosion) and a group with very high
      caries experience (caries) were chosen. Furthermore, the aim was to determine
      whether differences among groups could also be found on an individual level.
      RESULTS: Although it was not possible to retrieve three groups whose members were
      completely identical, the present study points in the direction that, on a group
      level, subjects with very little dental disease seemed to have a more favorable
      physicochemical saliva composition with respect to higher calcium, phosphate,
      bicarbonate, pH, degree of saturation with respect to hydroxyapatite and a lower
      critical pH (p < 0.05 or less). However, on an individual level the explanatory
      power for the saliva composition was only 10% for caries experience and only 11%
      for dental erosion (p < 0.001). CONCLUSION: The compositional analyses performed
      in this study on stimulated whole saliva, including major physicochemical
      characteristics of saliva, will most likely have little predictive value for
      future dental caries and erosion in single individuals.

PMID- 24308633
TI  - One-step colloidal synthesis of biocompatible water-soluble ZnS quantum
      dot/chitosan nanoconjugates.
AB  - Quantum dots (QDs) are luminescent semiconductor nanocrystals with great
      prospective for use in biomedical and environmental applications. Nonetheless,
      eliminating the potential cytotoxicity of the QDs made with heavy metals is still
      a challenge facing the research community. Thus, the aim of this work was to
      develop a novel facile route for synthesising biocompatible QDs employing
      carbohydrate ligands in aqueous colloidal chemistry with optical properties tuned
      by pH. The synthesis of ZnS QDs capped by chitosan was performed using a single
      step aqueous colloidal process at room temperature. The nanobioconjugates were
      extensively characterised by several techniques, and the results demonstrated
      that the average size of ZnS nanocrystals and their fluorescent properties were
      influenced by the pH during the synthesis. Hence, novel 'cadmium-free'
      biofunctionalised systems based on ZnS QDs capped by chitosan were successfully
      developed exhibiting luminescent activity that may be used in a large number of
      possible applications, such as probes in biology, medicine and pharmacy. 

PMID- 24308634
TI  - A base substitution in the donor site of intron 12 of KIT gene is responsible for
      the dominant white coat colour of blue fox (Alopex lagopus).
AB  - The dominant white coat colour of farmed blue fox is inherited as a monogenic
      autosomal dominant trait and is suggested to be embryonic lethal in the
      homozygous state. In this study, the transcripts of KIT were identified by RT-PCR
      for a dominant white fox and a normal blue fox. Sequence analysis showed that the
      KIT transcript in normal blue fox contained the full-length coding sequence of
      2919 bp (GenBank Acc. No KF530833), but in the dominant white individual, a
      truncated isoform lacking the entire exon 12 specifically co-expressed with the
      normal transcript. Genomic DNA sequencing revealed that a single nucleotide
      polymorphism (c.1867+1G>T) in intron 12 appeared only in the dominant white
      individuals and a 1-bp ins/del polymorphism in the same intron showed in
      individuals representing two different coat colours. Genotyping results of the
      SNP with PCR-RFLP in 185 individuals showed all 90 normal blue foxes were
      homozygous for the G allele, and all dominant white individuals were
      heterozygous. Due to the truncated protein with a deletion of 35 amino acids and
      an amino acid replacement (p.Pro623Ala) located in the conserved ATP binding
      domain, we propose that the mutant receptor had absent tyrosine kinase activity.
      These findings reveal that the base substitution at the first nucleotide of
      intron 12 of KIT gene, resulting in skipping of exon 12, is a causative mutation
      responsible for the dominant white phenotype of blue fox.

PMID- 24308635
TI  - Pirfenidone for the treatment of idiopathic pulmonary fibrosis.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and
      lethal fibrosing interstitial pneumonia. The median survival from the onset of
      the symptoms is 2.8 - 4.2 years and the 5-year survival rate is 20%. Its poor
      prognosis, combined with the scarcity of treatment options, provides a strong
      rationale for the development of novel therapeutic strategies. During the past
      decade there has been a huge rise in clinical trials with anti-fibrotic drugs,
      although only pirfenidone (Esbriet) has shown a beneficial effect. AREAS COVERED:
      This article reviews the medical literature on the effectiveness and safety of
      pirfenidone in IPF, by means of a PubMed search from 1995 to present, completed
      with some data on file from the manufacturer. EXPERT OPINION: Pirfenidone is the
      only anti-fibrotic drug approved for the treatment of IPF. Pirfenidone provides a
      meaningful clinical effect on reductions in the decrease in forced vital capacity
      (FVC), six-minute walk test (6MWT) distance and mortality, and it improves the
      progression-free survival in IPF patients with mild-to-moderate disease.
      Pirfenidone is well tolerated, with the most common side-effects being
      gastrointestinal discomfort and photosensitivity. Pirfenidone has a favorable
      benefit-risk profile and represents a suitable treatment option for patients with
      mild-to-moderate IPF.

PMID- 24308636
TI  - Polycationic ligands in gold catalysis: synthesis and applications of extremely
      pi-acidic catalysts.
AB  - Very often ligands are anionic or neutral species. Cationic ones are rare, and,
      when used, the positively charged groups are normally appended to the periphery
      of the ligand. Here, we describe a dicationic phosphine with no spacer between
      the phosphorus atom and the two positively charged groups. This structural
      feature makes its donor ability poorer than that of phosphites and only
      comparable to extremely toxic or pyrophoric compounds such as PF3 or P(CF3)3. By
      exploiting these properties, a new Au catalyst has been developed displaying a
      dramatically enhanced capacity to activate pi-systems. This has been used to
      synthesize very sterically hindered and naturally occurring 4,5-disubstituted
      phenanthrenes. The present approach is expected to be applicable to the
      development and improvement of many other transition metal catalyzed
      transformations that benefit from extremely strong pi-acceptor ligands. The
      mechanism of selected catalytic transformations has been explored by density
      functional calculations. 

PMID- 24308637
TI  - Lack of metabolic activation and predominant formation of an excreted metabolite
      of nontoxic platynecine-type pyrrolizidine alkaloids.
AB  - Pyrrolizidine alkaloid (PA) poisoning is well-known because of the intake of PA
      containing plant-derived natural products and PA-contaminated foodstuffs. Based
      on different structures of the necine bases, PAs are classified into three types:
      retronecine, otonecine, and platynecine type. The former two type PAs possessing
      an unsaturated necine base with a 1,2-double bond are hepatotoxic due to the P450
      mediated metabolic activation to generate reactive pyrrolic ester, which
      interacts with cellular macromolecules leading to toxicity. With a saturated
      necine base, platynecine-type PAs are reported to be nontoxic and their
      nontoxicity was hypothesized to be due to the absence of metabolic activation;
      however, the metabolic pathway responsible for their nontoxic nature is largely
      unknown. In the present study, to prove the absence of metabolic activation in
      nontoxic platynecine-type PAs, hepatic metabolism of platyphylline (PLA), a
      representative platynecine-type PA, was investigated and directly compared with
      the representatives of two toxic types of PAs in parallel. By determining the
      pyrrolic ester-derived glutathione conjugate, our results confirmed that the
      major metabolic pathway of PLA did not lead to formation of the reactive pyrrolic
      ester. More interestingly, having a metabolic rate similar to that of toxic PAs,
      PLA also underwent oxidative metabolisms mediated by P450s, especially P450 3A4,
      the same enzyme that catalyzes metabolic activation of two toxic types of PAs.
      However, the predominant oxidative dehydrogenation pathway of PLA formed a novel
      metabolite, dehydroplatyphylline carboxylic acid, which was water-soluble,
      readily excreted, and could not interact with cellular macromolecules. In
      conclusion, our study confirmed that the saturated necine bases determine the
      absence of metabolic activation and thus govern the metabolic pathway responsible
      for the nontoxic nature of platynecine-type PAs. 

PMID- 24308638
TI  - In-gel microwave-assisted acid hydrolysis of proteins combined with liquid
      chromatography tandem mass spectrometry for mapping protein sequences.
AB  - We report an enabling method for mapping the protein sequence with high sequence
      coverage. This method combines the high separation power of gel electrophoresis
      for protein separation with the high sequence coverage capability of microwave
      assisted acid hydrolysis (MAAH) mass spectrometry (MS). In-gel MAAH using 25%
      trifluoroacetic acid was developed and optimized for degrading the gel-separated
      protein into small peptides suitable for tandem MS sequencing. For bovine serum
      albumin (BSA) (~67 kDa), with 4 MUg of protein loading onto a gel for separation,
      followed by excising the protein gel band for in-gel MAAH and then injecting ~2
      MUg of the resultant peptides into a liquid chromatography quadrupole time-of
      flight mass spectrometer for analysis, 689 +/- 54 (n = 3) unique peptides were
      identified with a protein sequence coverage of 99 +/- 1%. Both the number of
      peptides detected and sequence coverage decreased as the sample amount decreased,
      mainly due to background interference: 316 +/- 59 peptides and 94 +/- 3% coverage
      for 2 MUg loading, 136 +/- 19 and 76 +/- 5% for 1 MUg loading, and 30 +/- 2 and
      32 +/- 2% for 0.5 MUg loading. To demonstrate the general applicability of the
      method, 10 gel bands from gel electrophoresis of an albumin-depleted human plasma
      sample were excised for in-gel MAAH LC-MS analysis. In total, 19 relatively high
      abundance proteins with molecular weights ranging from ~8 to ~160 kD could be
      mapped with coverage of 100% for six proteins (MW 8759 to 68 425 Da), 96-98% for
      five proteins (MW 11 458 to 36 431 Da), 92% for three proteins (MW 15 971 to 36
      431 Da), 80-87% for four proteins (MW 42 287 to 162 134 Da), and 56% for one
      protein (MW 51 358 Da). Finally, to demonstrate the applicability of the method
      for more detailed analysis of complex protein mixtures, two-dimensional (2D) gel
      electrophoresis was combined with in-gel MAAH, affinity purification, and LC
      MS/MS to characterize six bovine alpha-S1-casein phosphoprotein isoforms. Full
      sequence coverage was achieved for each protein, and six new modification sites
      were found. 

PMID- 24308639
TI  - Sieving of hot gases by hyper-cross-linked nanoscale-hybrid membranes.
AB  - Macromolecular networks consisting of homogeneously distributed covalently bonded
      inorganic and organic precursors are anticipated to show remarkable
      characteristics, distinct from those of the individual constituents. A novel
      hyper-cross-linked ultrathin membrane is presented, consisting of a giant
      molecular network of alternating polyhedral oligomeric silsesquioxanes and
      aromatic imide bridges. The hybrid characteristics of the membrane are manifested
      in excellent gas separation performance at elevated temperatures, providing a new
      and key enabling technology for many important industrial scale applications. 

PMID- 24308640
TI  - Circulating PCSK9 is a strong determinant of plasma triacylglycerols and total
      cholesterol in homozygous carriers of apolipoprotein epsilon2.
AB  - Homozygous carriers of the apolipoprotein epsilon2 allele are at risk of type III
      hyperlipidaemia, but do not necessarily develop this lipid disorder. In the
      present study, we have investigated the role of circulating PCSK9 (pro-protein
      convertase subtilisin kexin type 9), an important regulator of LDL (low-density
      lipoprotein) receptor expression, in the development of this hyperlipidaemic
      phenotype. In an observational study, plasma PCSK9 was measured in homozygous
      carriers of apolipoprotein epsilon2 (epsilon2/epsilon2; n=12), normal controls
      (n=72) and hypertriglyceridaemic patients with FCHL (familial combined
      hyperlipidaemia; n=38), who served as a hyperlipidaemic reference group.
      Cholesterol, triacylglycerols (triglycerides) and apolipoprotein B content in
      VLDL (very-low-density lipoprotein) and LDL particles was determined by
      ultracentrifugation in epsilon2/epsilon2 and FCHL patients. Median circulating
      PCSK9 levels did not differ between epsilon2/epsilon2 carriers compared with
      controls and hypertriglyceridaemic FCHL patients (84.5 compared with 82.0 and
      84.9 ng/ml; P=0.2 and 0.6 respectively). Circulating PCSK9 was associated with
      total cholesterol and triacylglycerols levels in epsilon2/epsilon2 carriers
      (P<0.05). These associations were stronger in epsilon2/epsilon2 carriers when
      compared with controls (P values for interaction=0.01 and 0.02 respectively). A
      direct comparison with FCHL patients demonstrated a similar discrepancy for the
      association with plasma triacylglycerols and also VLDL-apolipoprotein B,
      cholesterol and triacylglycerols (P value for interaction=0.01, 0.01, 0.03 and
      0.03 respectively). Plasma PCSK9 is associated with type III hyperlipidaemia. Its
      strong relationship with plasma triacylglycerols and total cholesterol
      distinguishes epsilon2/epsilon2 carriers from controls and another type of
      dyslipidaemia, which provides valuable information regarding the pathogenesis of
      this complex dyslipidaemia. Furthermore, these results suggest that patients with
      type III hyperlipidaemia may benefit from PCSK9-antagonizing therapy. 

PMID- 24308641
TI  - The genome of the Lactobacillus sanfranciscensis temperate phage EV3.
AB  - BACKGROUND: Bacteriophages infection modulates microbial consortia and
      transduction is one of the most important mechanism involved in the bacterial
      evolution. However, phage contamination brings food fermentations to a halt
      causing economic setbacks. The number of phage genome sequences of lactic acid
      bacteria especially of lactobacilli is still limited. We analysed the genome of a
      temperate phage active on Lactobacillus sanfranciscensis, the predominant strain
      in type I sourdough fermentations. RESULTS: Sequencing of the DNA of EV3 phage
      revealed a genome of 34,834 bp and a G + C content of 36.45%. Of the 43 open
      reading frames (ORFs) identified, all but eight shared homology with other phages
      of lactobacilli. A similar genomic organization and mosaic pattern of identities
      align EV3 with the closely related Lactobacillus vaginalis ATCC 49540 prophage.
      Four unknown ORFs that had no homologies in the databases or predicted functions
      were identified. Notably, EV3 encodes a putative dextranase. CONCLUSIONS: EV3 is
      the first L. sanfranciscensis phage that has been completely sequenced so far.

PMID- 24308642
TI  - Reformulating partially hydrogenated vegetable oils to maximise health gains in
      India: is it feasible and will it meet consumer demand?
AB  - BACKGROUND: The consumption of partially hydrogenated vegetable oils (PHVOs) high
      in trans fat is associated with an increased risk of cardiovascular disease and
      other non-communicable diseases. In response to high intakes of PHVOs, the Indian
      government has proposed regulation to set limits on the amount of trans fat
      permissible in PHVOs. Global recommendations are to replace PHVOs with
      polyunsaturated fatty acids (PUFAs) in order to optimise health benefits;
      however, little is known about the practicalities of implementation in low-income
      settings. The aim of this study was to examine the technical and economic
      feasibility of reducing trans fat in PHVOs and reformulating it using healthier
      fats. METHODS: Thirteen semi-structured interviews were conducted with
      manufacturers and technical experts of PHVOs in India. Data were open-coded and
      organised according to key themes. RESULTS: Interviewees indicated that
      reformulating PHVOs was both economically and technically feasible provided that
      trans fat regulation takes account of the food technology challenges associated
      with product reformulation. However, there will be challenges in maintaining the
      physical properties that consumers prefer while reducing the trans fat in PHVOs.
      The availability of input oils was not seen to be a problem because of the low
      cost and high availability of imported palm oil, which was the input oil of
      choice for industry. Most interviewees were not concerned about the potential
      increase in saturated fat associated with increased use of palm oil and were not
      planning to use PUFAs in product reformulation. Interviewees indicated that many
      smaller manufacturers would not have sufficient capacity to reformulate products
      to reduce trans fat. CONCLUSIONS: Reformulating PHVOs to reduce trans fat in
      India is feasible; however, a collision course exists where the public health
      goal to replace PHVOs with PUFA are opposed to the goals of industry to produce a
      cheap alternative product that meets consumer preferences. Ensuring that product
      reformulation is done in a way that maximises health benefits will require shifts
      in knowledge and subsequent demand of products, decreased reliance on palm oil,
      investment in research and development and increased capacity for smaller
      manufacturers.

PMID- 24308643
TI  - Repeated open endotracheal suctioning causes gradual desaturation but does not
      exacerbate lung injury compared to closed endotracheal suctioning in a rabbit
      model of ARDS.
AB  - BACKGROUND: Although endotracheal suctioning induces alveolar derecruitment
      during mechanical ventilation, it is not clear whether repeated endotracheal
      suctioning exacerbates lung injuries. The present study aimed to determine
      whether repeated open endotracheal suctioning (OS) exacerbates lung injury
      compared to closed endotracheal suctioning (CS) during mechanical ventilation in
      an animal model of acute respiratory distress syndrome (ARDS). METHODS: Briefly,
      thirty six Japanese white rabbits were initially ventilated in pressure
      controlled mode with a constant tidal volume (6 mL/kg). Then, lung injury was
      induced by repeated saline lavage. The rabbits were divided into four groups,
      namely: a) OS; b) CS; c) control with ARDS only; d) and healthy control (HC)
      without ARDS. Animals in all the groups were then ventilated with positive end
      expiratory pressure (PEEP) at 10 cm H2O. CS was performed using 6 French-closed
      suctioning catheters connected to endotracheal tube under the following
      conditions: a) a suctioning time and pressure of 10 sec and 140 mm Hg,
      respectively; and b) a suction depth of 2 cm (length of adapter) plus tracheal
      tube. OS was performed using the same conditions described for CS, except the
      ventilator was disconnected from the animals. Each endotracheal suctioning was
      performed at an interval of 30 min. RESULTS: PaO2/FIO2 (P/F) ratio for CS,
      control and HC groups remained at >400 for 6 hours, whereas that of the OS group
      progressively declined to 300 (p < 0.05), with each suctioning. However, no
      difference was observed either in lung injury score (histology) or in the
      expression pattern of inflammatory cytokines (tumor necrosis factor-alpha and
      interleukin-6) after 6 hours between the OS and CS groups in the circulatory as
      well as the pulmonary tissues. CONCLUSIONS: Progressive arterial desaturation
      under conditions of repeated endotracheal suctioning is greater in OS than in CS
      time-dependently. However, OS does not exacerbate lung injury during mechanical
      ventilation when observed over a longer time span (6 hours) of repeated
      endotracheal suctioning, based on morphological and molecular analysis.

PMID- 24308644
TI  - Prevalence of persistent lipid abnormalities in statin-treated patients: Belgian
      results of the Dyslipidaemia International Study (DYSIS).
AB  - AIM: A substantial number of cardiovascular events are not prevented by statin
      therapy, which is still regarded as the first-line therapy for hyperlipidaemia.
      Insights into the prevalence of lipid abnormalities of statin-treated patients in
      Belgium are lacking and may shed light on an unmet medical need for optimal use
      of current lipid-lowering therapies. This study aims to assess the prevalence and
      types of persistent lipid abnormalities in patients receiving statin therapy in a
      real-life primary care setting in Belgium. METHODS: This cross-sectional cohort
      study was designed to estimate the prevalence of specific lipid abnormalities in
      statin-treated patients in Belgium. Total cholesterol, low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and
      triglycerides were recorded from the patients' medical record. Patient's total
      cardiovascular risk and corresponding lipid treatment goals were defined based on
      the recent European Society of Cardiology/European Atherosclerosis Society
      recommendations. RESULTS: Overall, 56.2% of the statin-treated patients were not
      at goal for LDL-C. Low HDL-C (< 40 mg dl(-1) in men, < 45 mg dl(-1) in women) and
      elevated triglycerides (> 150 mg dl(-1) ) were seen in 16.3% and 29.0% of
      patients, respectively. Very high-risk patients were more likely to have LDL-C
      not at goal (71.4% of them), while 60.0% of high-risk patients and 34.1% of
      moderate-risk patients were not at goal for LDL-C. Use of ezetimibe (10 mg) was
      strongly associated with meeting LDL-C goals (OR 16.9, p < 0.0001). CONCLUSION:
      In Belgium, lipid abnormalities remained highly prevalent despite statin
      treatment, with more than half of all patients not reaching their LDL-C treatment
      goal. This finding clearly indicates that more aggressive lipid-lowering
      treatment is required in clinical daily practice to achieve the goals of the
      current guidelines.

PMID- 24308645
TI  - Correlations between cytogenetic and molecular monitoring among patients with
      newly diagnosed chronic myeloid leukemia in chronic phase: post hoc analyses of
      the Rationale and Insight for Gleevec High-Dose Therapy study.
AB  - CONTEXT: Although bone marrow (BM) karyotyping has been the standard in
      monitoring patients with chronic myeloid leukemia, peripheral blood (PB)
      monitoring methods may be more convenient. OBJECTIVE: To conduct post hoc
      analyses of the Rationale and Insight for Gleevec High-Dose Therapy study to
      evaluate correlations between results of cytogenetic testing and molecular
      monitoring from BM and PB during the first 18 months of high-dose imatinib
      therapy, and between early and late molecular responses. DESIGN: Newly diagnosed
      patients with chronic-phase chronic myeloid leukemia received imatinib 400 mg
      twice daily and were monitored quarterly for up to 18 months. Cytogenetic testing
      was performed by karyotyping using BM or by fluorescence in situ hybridization
      using PB. Molecular testing was performed by quantitative reverse transcriptase
      polymerase chain reaction using BM and PB. RESULTS: Significant pairwise
      correlations were found between results obtained by karyotyping, fluorescence in
      situ hybridization, and quantitative reverse transcriptase polymerase chain
      reaction using PB or BM (all pairwise correlations >0.8; P < .001). At 12 months,
      cytogenetic response by karyotyping correlated well with response by fluorescence
      in situ hybridization. A median 2.579-log reduction in BCR-ABL1 level from a
      standardized baseline correlated with fluorescence in situ hybridization-negative
      status. Patients with greater than 2-log reduction in BCR-ABL1 level at 3, 6, and
      9 months were more likely to achieve major molecular response at 18 months than
      those with 2-log reduction or less. CONCLUSIONS: Our findings support the
      feasibility of molecular monitoring using PB and suggest that molecular
      monitoring conducted at a single reliable reference laboratory can adequately
      track response without invasive BM testing. Our findings are consistent with
      other work indicating that early response to imatinib predicts favorable long
      term outcome.

PMID- 24308646
TI  - Rapamycin decreases DNA damage accumulation and enhances cell growth of WRN
      deficient human fibroblasts.
AB  - Werner syndrome (WS), caused by mutations at the WRN helicase gene, is a
      progeroid syndrome characterized by multiple features consistent with accelerated
      aging. Aberrant double-strand DNA damage repair leads to genomic instability and
      reduced replicative lifespan of somatic cells. We observed increased autophagy in
      WRN knockdown cells; this was further increased by short-term rapamycin
      treatment. Long-term rapamycin treatment resulted in improved growth rate,
      reduced accumulation of DNA damage foci and improved nuclear morphology;
      autophagy markers were reduced to near-normal levels, possibly due to clearance
      of damaged proteins. These data suggest that protein aggregation plays a role in
      the development of WS phenotypes and that the mammalian target of rapamycin
      complex 1 pathway is a potential therapeutic target of WS.

PMID- 24308647
TI  - Hinokitiol inhibits cell growth through induction of S-phase arrest and apoptosis
      in human colon cancer cells and suppresses tumor growth in a mouse xenograft
      experiment.
AB  - Hinokitiol (1), a tropolone-related natural compound, induces apoptosis and has
      anti-inflammatory, antioxidant, and antitumor activities. In this study, the
      inhibitory effects of 1 were investigated on human colon cancer cell growth and
      tumor formation of xenograft mice. HCT-116 and SW-620 cells derived from human
      colon cancers were found to be similarly susceptible to 1, with IC50 values of
      4.5 and 4.4 MUM, respectively. Compound 1 induced S-phase arrest in the cell
      cycle progression and decreased the expression levels of cyclin A, cyclin E, and
      Cdk2. Conversely, 1 increased the expression of p21, a Cdk inhibitor. Compound 1
      decreased Bcl-2 expression and increased the expression of Bax, and cleaved
      caspase-9 and -3. The effect of 1 on tumor formation when administered orally was
      evaluated in male BALB/c-nude mice implanted intradermally separately with HCT
      116 and SW-620 cells. Tumor volumes and tumor weights in the mice treated with 1
      (100 mg/kg) were decreased in both cases. These results suggest that the
      suppression of tumor formation by compound 1 in human colon cancer may occur
      through cell cycle arrest and apoptosis. 

PMID- 24308649
TI  - Mitochondrial introgressive hybridization following a demographic expansion in
      the tomato frogs of Madagascar, genus Dyscophus.
AB  - Madagascar is a biodiversity hotspot with a unique fauna and flora largely
      endemic at the species level and highly threatened by habitat destruction. The
      processes underlying population-level differentiation in Madagascar's biota are
      poorly understood and have been proposed to be related to Pleistocene climatic
      cycles, yet the levels of genetic divergence observed are often suggestive of
      ancient events. We combined molecular markers of different variability to assess
      the phylogeography of Madagascar's emblematic tomato frogs (Dyscophus guineti and
      D. antongilii) and interpret the observed pattern as resulting from ancient and
      recent processes. Our results suggest that the initial divergence between these
      taxa is probably old as reflected by protein-coding nuclear genes and by a strong
      mitochondrial differentiation of the southernmost population. Dramatic changes in
      their demography appear to have been triggered by the end of the last glacial
      period and possibly by the short return of glacial conditions known as the 8K
      event. This dramatic change resulted in an approximately 50-fold reduction of the
      effective population size in various populations of both species. We hypothesize
      these species' current mitochondrial DNA diversity distribution reflects a
      swamping of the mitochondrial genetic diversity of D. guineti by that of D.
      antongilii previous to the populations' bottlenecks during the Holocene, and
      probably as a consequence of D. antongilii demographic expansion approximately 1
      million years ago. Our data support the continued recognition of D. antongilii
      and D. guineti as separate species and flag D. guineti as the more vulnerable
      species to past and probably also future environmental changes. 

PMID- 24308651
TI  - Factors associated with quality of life among family members of patients with
      dementia in Cyprus.
AB  - BACKGROUND: Numerous studies have reported that caring for a person with dementia
      is a stressful experience. Nevertheless, quality of life (QoL) measures have
      commonly focused on patients, while factors that influence caregivers' QoL have
      not been clearly identified. In order to contribute to the understanding of
      caregivers' QoL, we explored how QoL among caregivers is related to their
      perceived level of burden, their reported number of depressive symptoms, and the
      level of care recipients' dependency. METHODS: Seventy-six caregivers referred by
      the two main referral centers of patients with dementia in Cyprus participated in
      a cross-sectional survey with a descriptive correlational design. Caregivers
      completed four instruments, measuring burden (ZBI), depression (CES-D), quality
      of life-Alzheimer's disease (QoL-AD), and activities of daily living (ADL) of the
      care recipients and provided socio-demographic information. RESULTS: The majority
      of the participants scored high levels of burden (M = 43.32/SD = 15.23) and
      depression (59.2% scored over the cut-off point of 16). QoL was only moderate (M
      = 30.89/SD = 8.21) and negatively correlated with burden (r = -32, p = 0.01) and
      depression (r = -0.296, p < 0.05). Only a weak correlation was observed between
      QoL and ADL (r = 0.167, p = 0.15). Hierarchical multiple regression analyses
      revealed that overall burden scores and income were associated with QoL,
      explaining 20% of the overall variance of the caregiver's QoL. CONCLUSION:
      Further research is necessary to investigate which additional domains determine
      QoL and further our understanding of the factors that may reduce the burden
      imposed on dementia caregivers.

PMID- 24308648
TI  - Relative importance of pollen and seed dispersal across a Neotropical mountain
      landscape for an epiphytic orchid.
AB  - Populations of many species are isolated within narrow elevation bands of
      Neotropical mountain habitat, and how well dispersal maintains genetic
      connectivity is unknown. We asked whether genetic structure of an epiphytic
      orchid, Epidendrum firmum, corresponds to gaps between Costa Rican mountain
      ranges, and how these gaps influence pollen and seed flow. We predicted that
      significant genetic structure exists among mountain ranges due to different
      colonization histories and limited gene flow. Furthermore, we predicted that
      pollen movement contributes more to gene flow than seeds because seeds are
      released into strong winds perpendicular to the narrow northwest-southeast
      species distribution, while the likely pollinators are strong fliers. Individuals
      from 12 populations and three mountain ranges were genotyped with nuclear
      microsatellites (nDNA) and chloroplast sequences (cpDNA). Genetic diversity was
      high for both markers, while nDNA genetic structure was low (FSTn  = 0.020) and
      cpDNA structure was moderate (FSTc  = 0.443). Significant cpDNA barriers occurred
      within and among mountain ranges, but nDNA barriers were not significant after
      accounting for geographic distance. Consistent with these contrasting patterns of
      genetic structure, pollen contributes substantially more to gene flow among
      populations than seed (mp /ms  = 46). Pollinators mediated extensive gene flow,
      eroding nDNA colonization footprints, while seed flow was comparatively limited,
      possibly due to directional prevailing winds across linearly distributed
      populations. Dispersal traits alone may not accurately inform predictions about
      gene flow or genetic structure, supporting the need for research into the
      potentially crucial role of pollinators and landscape context in gene flow among
      isolated populations. 

PMID- 24308652
TI  - The use of portable monitoring for sleep apnea diagnosis in adults.
AB  - Due to increasing demand for sleep services, there has been growing interest in
      ambulatory models of care for patients with obstructive sleep apnea (OSA). The
      implementation of alternative approaches to the current management by full
      polysomnography (PSG) in the sleep laboratory is necessary for diagnosing this
      syndrome due to the high cost of full-night PSG. A good alternative option for
      OSA diagnosis is portable monitoring (PM), which is known for its accuracy, ease
      of management and lower cost when compared with full PSG. PM has not been well
      validated for OSA diagnosis in patients with medical comorbidities or in elderly
      individuals and children. PM may be recommended as an alternative method to PSG
      for patients with high clinical risk for OSA. In the present review, we describe
      the use of PM for OSA diagnosis and evaluate the current progress, costs,
      limitations and applications of these devices in various groups of patients,
      particularly for patients with comorbid diseases. 

PMID- 24308653
TI  - Interferon-gamma release assays for tuberculosis: current and future
      applications.
AB  - Interferon-gamma release assays (IGRAs) represent the first new tool to diagnose
      latent tuberculosis infection for more than 100 years. They have advantages over
      the traditional tuberculin skin test which has a poor specificity due to false
      positive responses in people who are BCG vaccinated as there is a cross
      reactivity of proteins present in both BCG and the tuberculin skin test. IGRAs
      rely on the concept of detecting the ex vivo release of the cytokine IFN-gamma, a
      key anti-Mycobacterium tuberculosis cytokine, from T cells which react
      specifically to antigens from M. tuberculosis. T cells are sensitized to the
      antigens in vivo, and then react when they encounter the same proteins ex vivo.
      The readouts are used to determine presence of sensitized cells, acting as a
      surrogate for latent tuberculosis infection. IGRAs are now being incorporated
      into national guidance for diagnosis and research is ongoing into next-generation
      versions of the test. 

PMID- 24308654
TI  - Vaccines for children and adults with chronic lung disease: efficacy against
      acute exacerbations.
AB  - Acute exacerbations of chronic lung disease are usually associated with viral and
      bacterial pathogens. They contribute to declining lung function, poor quality of
      life and exert an excess burden on individuals, families, communities and the
      healthcare sector. Hence, preventing exacerbations is important in clinical
      management. Several vaccines providing protection against respiratory pathogens
      (Streptococcus pneumoniae, Bordetella pertussis and influenza) that can trigger
      exacerbations are available, but evidence to support their effectiveness in
      preventing exacerbations of chronic lung disease is limited. Candidate vaccines
      in pre-clinical or clinical development phases include those targeting
      Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas
      aeruginosa, respiratory syncytial virus and human rhinoviruses. However, it is
      likely to be several years before vaccines against these pathogens are available
      for children and adults with chronic lung diseases. For vaccination to play an
      important role in managing chronic lung disease efforts need to be directed at
      understanding how various pathogens cause exacerbations and alter long-term lung
      function. 

PMID- 24308655
TI  - Hydrogen sulfide as a potential biomarker of asthma.
AB  - Hydrogen sulfide (H2S), a gas characterized by the odor of rotten eggs, is
      produced by many cells in the airways and lungs, and may regulate physiologic and
      pathophysiologic processes. It plays a role in cellular signaling, and represents
      the third gasotransmitter after nitric oxide and carbon monoxide. Endogenous and
      exogenous H2S have anti-inflammatory and anti-proliferative effects, with
      inhibitory effects in models of lung inflammation and fibrosis. Under certain
      conditions, H2S may also be proinflammatory. It is generally a vasodilator and
      relaxant of airway and vascular smooth muscle cells. It acts as a reducing agent,
      being able to scavenge superoxide and peroxynitrite. H2S is detectable in serum
      and in sputum supernatants with raised levels observed in asthmatics. The sputum
      levels correlated inversely with lung function. H2S may play a role in the
      pathogenesis of asthma.

PMID- 24308656
TI  - VeriStrat: a prognostic and/or predictive biomarker for advanced lung cancer
      patients?
AB  - The role of EGF receptor (EGFR) inhibitors in the treatment of lung cancer
      without activating EGFR mutations has been a controversial issue, particularly
      their relative efficacy over the available chemotherapy in the second- and third
      line setting. VeriStrat is a serum/plasma proteomic test developed using matrix
      assisted laser desorption/ionization methodology, aiming at predicting benefit
      from EGFR treatment. The VeriStrat algorithm has been interrogated
      retrospectively and prospectively in samples from randomised trials, such as the
      PROSE study, confirming the prognostic information associated with the signature.
      In addition, the test appeared to be predictive of erlotinib impact on survival,
      as only VeriStrat Good patients benefited from such a treatment. Additional
      studies should confirm and further define its role in predicting EGFR tyrosine
      kinase inhibitor benefit, and to establish its better use in terms of clinical
      efficiency identifying which patients are candidates for the test, at which time
      on the history of the disease, and lastly at what extra cost. 

PMID- 24308657
TI  - The role of caveolae in the pathophysiology of lung diseases.
AB  - Caveolae are flask-shaped plasma membrane invaginations formed by constitutive
      caveolin proteins and regulatory cavin proteins. Caveolae harbor a range of
      signaling components such as receptors, ion channels and regulatory molecules.
      There is now increasing evidence that caveolins and cavins play an important role
      in a variety of diseases. However, the mechanisms by which these caveolar
      proteins affect lung health and disease are still under investigation, with
      emerging data suggesting complex roles in disease pathophysiology. This review
      summarizes the current state of understanding of how caveolar proteins contribute
      to lung structure and function and how their altered expression and/or function
      can influence lung diseases. 

PMID- 24308658
TI  - Nine-month angiographic and intravascular ultrasound outcomes after resolute
      zotarolimus-eluting stent implantation for the treatment of in-stent restenosis.
AB  - OBJECTIVES: We aimed to evaluate the mid-term outcomes of resolute zotarolimus
      eluting stent (R-ZES) implantation for in-stent restenosis (ISR). BACKGROUND:
      There has been a paucity of data regarding the effects of new-generation drug
      eluting stent to treat ISR. METHODS: From 2009 to 2010, a total of 98 patients
      with 98 ISR lesions were prospectively enrolled after R-ZES implantation for the
      treatment of ISR. Among 98 patients, 73 patients underwent follow-up angiography
      at 9 months. Serial intravascular ultrasound (IVUS) at both postprocedure and 9
      months was evaluated in 55 patients. The overlapped segment of R-ZES was defined
      as the portion of R-ZES superimposed on previous stent. RESULTS: Late loss and
      binary restenosis rate were 0.3 +/- 0.5 mm and 5.5% at 9 months. On IVUS, the
      percentage of neointimal volume and maximum percentage of neointimal area were
      3.9 +/- 6.3% and 17.3 +/- 15.5%, respectively. There was no significant change of
      vessel volume index between postprocedure and 9 months (16.9 +/- 4.7 mm3 /mm vs.
      17.1 +/- 4.6 mm3 /mm, P = 0.251). Late-acquired incomplete stent apposition was
      observed in 5 (5/55, 9.1%) cases. Compared with nonoverlapped segments of R-ZES,
      the overlapped did not show larger neointimal volume index (0.3 +/- 0.5 mm3 /mm
      vs. 0.2 +/- 0.3 mm3 /mm, P = 0.187) on 9-month IVUS. During follow-up (median,
      353 days), repeat target-lesion revascularization was performed in four cases,
      but there were no death or stent thrombosis. CONCLUSIONS: This study suggested
      that R-ZES implantation for the treatment of ISR was effective up to 9 months and
      showed favorable vascular responses on serial IVUS assessment.

PMID- 24308659
TI  - Rotational atherectomy as endovascular haute couture: a road map of tools and
      techniques for the interventional management of burr entrapment.
AB  - OBJECTIVES AND BACKGROUND: Rotational atherectomy (RA) is used as a debulking
      technique prior to stenting in some specialized cardiac centers for calcified
      coronary lesions amenable to percutaneous coronary intervention (PCI). A specific
      possible complication, burr entrapment, is unusual but carries serious risks and
      may sometimes necessitate surgery as a rescue procedure. However, different
      modalities using a percutaneous approach were proposed as a bail-out. We aim to
      propose a framework for possible management for trapped RA burr. METHODS AND
      RESULTS: A literature review of the most relevant cases of entrapped burr during
      PCI was performed. Twelve cases were reported and different solutions were
      discussed. Surgery was needed in only 1 patient to retrieve the trapped burr, and
      in all the other cases, different percutaneous solutions were successful to
      retract the trapped device. CONCLUSIONS: These cases illustrate that burr
      entrapment during RA, albeit rare, may occur and may transform a relatively
      simple PCI to a procedure failure. Although prevention is better than treatment,
      the operators should be aware of such serious complication and they should keep
      in mind that various possible percutaneous solutions may be successful to
      retrieve the burr and to avoid surgery.

PMID- 24308660
TI  - Variability in maximal suggested door-in-door-out time for hospitals transferring
      patients for primary angioplasty in STEMI.
AB  - OBJECTIVES: We derived a formula for maximal suggested door-in-door-out time
      (DIDO) for hospitals that do not perform primary percutaneous coronary
      intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND:
      Efforts to minimize DIDO at non-PCI hospitals can improve door-to-balloon time
      (D2B). Targeting a maximal suggested DIDO for a transferring hospital can
      influence reperfusion strategy. METHODS: We examined time to treatment intervals
      for 193 STEMI patients who underwent primary PCI at our hospital. D2B in
      transferred patients (D2BT ) was divided into 3 intervals: transferring hospital
      DIDO, inter-hospital transport time, and interventional time. We defined maximal
      suggested DIDO as the maximum DIDO that would allow PCI with D2BT <= 120 minutes.
      RESULTS: D2B was higher in transfer compared to on-site patients (147 +/- 52 vs.
      75 +/- 44 minutes, P < 0.0001). In transfer patients, treatment time intervals
      were: DIDO 80 +/- 42 minutes, transport time 37 +/- 18 minutes, interventional
      time 35 +/- 16 minutes. The greatest variability in D2BT was related to DIDO. We
      estimated that maximal suggested DIDO = [120 - (transport time plus
      interventional time)]. Using a fixed interventional time of 40 minutes, we
      simplified this as: maximal DIDO = 80 - transport time. Maximal suggested DIDO
      for 4 transferring hospitals in our network ranged from 1 to 65 minutes. DIDO
      under the hospital-specific threshold was the strongest predictor of achieving
      D2BT <120 minutes. CONCLUSIONS: Transferring hospitals' maximal suggested DIDO is
      variable, and can be calculated from inter-hospital transport time. Instead of a
      universal target DIDO (e.g., <30 minutes), maximal suggested DIDO can be
      calculated individually for each non-PCI hospital within a STEMI network.

PMID- 24308661
TI  - The hemorrhage of information to reduce bleeding complications after percutaneous
      coronary intervention.

PMID- 24308662
TI  - Scalable method for the fabrication and testing of glass-filled, three
      dimensionally sculpted extraordinary transmission apertures.
AB  - This Letter features a new, scalable fabrication method and experimental
      characterization of glass-filled apertures exhibiting extraordinary transmission.
      These apertures are fabricated with sizes, aspect ratios, shapes, and side-wall
      profiles previously impossible to create. The fabrication method presented
      utilizes top-down lithography to etch silicon nanostructures. These
      nanostructures are oxidized to provide a transparent template for the deposition
      of a plasmonic metal. Gold is deposited around these structures, reflowed, and
      the surface is planarized. Finally, a window is etched through the substrate to
      provide optical access. Among the structures created and tested are apertures
      with height to diameter aspect ratios of 8:1, constructed with rectangular,
      square, cruciform, and coupled cross sections, with tunable polarization
      sensitivity and displaying unique properties based on their sculpted side-wall
      shape. Transmission data from these aperture arrays is collected and compared to
      examine the role of spacing, size, and shape on their overall spectral response.
      The structures this Letter describes can have a variety of novel applications
      from the creation of new types of light sources to massively multiplexed
      biosensors to subdiffraction limit imaging techniques. 

PMID- 24308663
TI  - Strain analysis for the prediction of the preferential nucleation sites of
      stacked quantum dots by combination of FEM and APT.
AB  - The finite elements method (FEM) is a useful tool for the analysis of the strain
      state of semiconductor heterostructures. It has been used for the prediction of
      the nucleation sites of stacked quantum dots (QDs), but often using either
      simulated data of the atom positions or two-dimensional experimental data, in
      such a way that it is difficult to assess the validity of the predictions. In
      this work, we assess the validity of the FEM method for the prediction of stacked
      QD nucleation sites using three-dimensional experimental data obtained by atom
      probe tomography (APT). This also allows us to compare the simulation results
      with the one obtained experimentally. Our analysis demonstrates that FEM and APT
      constitute a good combination to resolve strain-stress problems of epitaxial
      semiconductor structures. 

PMID- 24308664
TI  - Comparative Analysis of Immune Responses in Pigs to High and Low Pathogenic
      Porcine Reproductive and Respiratory Syndrome Viruses Isolated in China.
AB  - The CH-1a and HuN4 strains of porcine reproductive and respiratory syndrome virus
      (PRRSV) show different pathogenicities in pigs. To understand host immune
      responses against these viruses, we investigated the dynamic changes in cytokine
      levels produced in peripheral blood of piglets infected with the highly
      pathogenic PRRSV HuN4 strain or the CH-1a strain. Clinical signs, virus loads and
      serum cytokine levels [interferon(IFN)-alpha, Interleukin (IL)-1, TNF-alpha, IL
      6, IL-12, IFN-gamma, IL-10 and TGF-beta] were tested. The results showed that
      while piglets developed effective cellular immune responses against CH-1a
      infection, those infected with HuN4 displayed ineffective cellular immunity,
      organ lesions and persistent elevated levels of immunoregulatory cytokines (IL-10
      and TGF-beta), which delayed the development of PRRSV-specific immune responses.
      These results demonstrated that HuN4 infection induced higher cytokine levels
      than that of CH-1a infection induced. The changes in inflammatory cytokines
      intensified the inflammatory reaction and damaged the tissues and organs. 

PMID- 24308665
TI  - Hematoma or "partial priapism" in the proximal part of the corpus cavernosum.
AB  - INTRODUCTION: "Partial priapism" is a rare disorder. Therapy is controversial in
      literature. AIM: To show that conservative treatment leads to a full functional
      recovery of this condition. METHODS: This report describes a case of a hematoma
      or "partial priapism" in the proximal part of the right corpus cavernosum.
      RESULTS: Complete functional recovery after conservative treatment with
      nonsteroidal anti-inflammatory drugs. CONCLUSION: "Partial priapism" probably
      represents a hematoma in the interstitium of the proximal part of the corpus
      cavernosum. Conservative treatment is advised.

PMID- 24308666
TI  - Differential diagnosis of vertigo and dizziness in the emergency department.
AB  - CONCLUSIONS: To establish a system of differential diagnosis for
      vertigo/dizziness at the Emergency Department (ED), careful history-taking of
      complications and examinations of nystagmus should be helpful and therefore
      prepared by ED staff. OBJECTIVES: Vertigo/dizziness could come from various kinds
      of organs for equilibrium, sometimes resulting in an emergency due to the central
      origin. In the present study, we checked patients' background data at the ED in
      advance of a definitive diagnosis at the Department of Otolaryngology and
      examined the significance of the correlation between the data and the diagnosis.
      METHODS: We studied a series of 120 patients with vertigo/dizziness, who visited
      the Departments of Emergency and Otolaryngology between April 2011 and March
      2012. At the ED, we first checked patients' backgrounds and carried out
      neurologic and neuro-otologic examinations. At the Department of Otolaryngology,
      we finally diagnosed all the patients according to the criteria and classified
      the origins of vertigo/dizziness into central and non-central diseases. RESULTS:
      The ratio of patients with disease of central origin was 12.5% and that for non
      central origin was 87.5%. The risk factors for cerebrovascular disease such as
      hypertension, heart disease, and diabetes were also the risk factors for central
      vertigo/dizziness by the chi-squared test. To predict a central origin for
      vertigo/dizziness, only gaze nystagmus was the significant factor by multivariate
      regression analysis.

PMID- 24308668
TI  - A genome-wide association study reveals a quantitative trait locus for age at
      first calving in delta/notch-like EGF repeat containing on chromosome 2 in
      Japanese Black cattle.
AB  - Age at first calving (AFC) is an important trait for achieving earlier
      reproductive performance in cattle. To identify quantitative trait loci for AFC
      in Japanese Black cattle, we conducted a genome-wide association study using 866
      animals with extreme AFC values selected from a larger group of 52, 009 animals.
      We identified single nucleotide polymorphisms (SNPs) on bovine chromosome 2 that
      were associated with AFC. These SNPs were located within 112.8-kbp intronic
      region of delta/notch-like EGF repeat containing (DNER) and proved to be in a
      state of high linkage disequilibrium. The association was replicated in an
      independent sample of 2963 animals. In the replicated population, the frequency
      of the reduced AFC allele (Q) was 0.463, and the allele accounts for 8% of the
      total genetic variance. The effect of allele substitution on AFC was a decrease
      of 11.54 days. The results suggest that the Q allele could serve as a useful
      marker in Japanese Black cattle to select animals with superior AFC performance.

PMID- 24308669
TI  - Changes in polysaccharide composition during sparkling wine making and aging.
AB  - The evolution in polysaccharide composition and molecular weights during
      sparkling wine making and aging was studied for the first time in this work.
      Different autochthonous grape varieties from Spain (Verdejo, Viura, Malvasia,
      Albarin, Godello, Garnacha and Prieto Picudo) were used to elaborate sparkling
      wines following the champenoise method. Principal component analysis showed
      differentiation of wines according to polysaccharide families. This
      differentiation was due to the process of aging on yeast lees, but not to the
      variety employed. The content of mannoproteins during aging was positively
      correlated (r = 0.792) with total polysaccharides from grapes. After six months
      of aging the highest content of mannoproteins and polysaccharides rich in
      arabinose and galactose was obtained. Also a shift to lower molecular weights was
      observed. The combination of these two characteristics could imply a better foam
      stability and thus sensory quality of sparkling wines. 

PMID- 24308670
TI  - Fluorometric measurement and modeling of droplet temperature changes in an
      electrospray plume.
AB  - The evolution of droplet temperatures in an electrospray plume was measured via
      ratiometric fluorescence. Under typical operating conditions, droplet
      temperatures decrease ~30 K over the first 5.0 mm along the spray axis, followed
      by a slight (~2-3 K) rewarming. Experimental axial profiles (Z-axis) were fit by
      use of diffusion-controlled and surface-controlled evaporation models. Both
      models fit the experimental data well for the cooling portion of the spray
      (Pearson correlation coefficient R >= 0.994), but the surface-controlled model
      required unrealistic droplet radius values to obtain a good fit. In lateral
      profiles at a given Z near the emitter tip, temperatures are lower (by 3.0-10 K)
      in the periphery than on the spray axis. This behavior is consistent with the
      expected enrichment of the spray periphery with smaller droplets. At longer axial
      distances, lateral profiles were relatively flat. Droplet temperature as a
      function of axial displacement fell more rapidly at lower liquid flow rates,
      possibly attributable to changes in droplet size and/or velocity with flow rate. 

PMID- 24308671
TI  - Report of a novel KIR3DS1*0130104 allele discovered using advanced molecular
      techniques.
AB  - KIR3DS1*0130104 is identical to KIR3DS1*0130101 except for changes at positions
      1768 (C>T) and 12617 (C>A). 

PMID- 24308672
TI  - Efficacy of low-dose intra-articular tranexamic acid in total knee replacement; a
      prospective triple-blinded randomized controlled trial.
AB  - BACKGROUND: Recently, a number of studies using intra-articular application of
      tranexamic acid (IA-TXA), with different dosage and techniques, successfully
      reduced postoperative blood loss in total knee replacement (TKR). However, best
      of our knowledge, the very low dose of IA-TXA with drain clamping technique in
      conventional TKR has not been yet studied. This study aimed to evaluate the
      effectiveness and dose-response effect of two low-dose IA-TXA regimens in
      conventional TKR on blood loss and blood transfusion reduction. METHODS: Between
      2010 and 2011, a triple-blinded randomized controlled study was conducted in 135
      patients undergoing conventional TKR. The patients were allocated into three
      groups according to intra-articular solution received: Control group (physiologic
      saline), TXA-250 group (TXA 250 mg), and TXA-500 group (TXA 500 mg). The solution
      was injected after wound closure followed by drain clamping for 2 hours. Blood
      loss and transfusion were recorded. Duplex ultrasound was performed. Functional
      outcome and complication were followed for one year. RESULTS: There were forty
      five patients per groups. The mean total hemoglobin loss was 2.9 g/dL in control
      group compared with 2.2 g/dL in both TXA groups (p > 0.001). Ten patients (22%,
      control), six patients (13%, TXA-250) and none (TXA-500) required transfusion (p
      = 0.005). Thromboembolic events were detected in 7 patients (4 controls, 1 TXA
      250, and 2 TXA-500). Functional outcome was non-significant difference between
      groups. CONCLUSIONS: Combined low-dose IA-TXA, as 500 mg, with 2-hour clamp drain
      is effective for reducing postoperative blood loss and transfusion in
      conventional TKR without significant difference in postoperative knee function or
      complication. TRIAL REGISTRATION: ClinicalTrials.gov NCT01850394.

PMID- 24308673
TI  - Infarct quantification using 3D inversion recovery and 2D phase sensitive
      inversion recovery; validation in patients and ex vivo.
AB  - BACKGROUND: Cardiovascular-MR (CMR) is the gold standard for quantifying
      myocardial infarction using late gadolinium enhancement (LGE) technique. Both 2D-
      and 3D-LGE-sequences are used in clinical practise and in clinical and
      experimental studies for infarct quantification. Therefore the aim of this study
      was to investigate if image acquisitions with 2D- and 3D-LGE show the same
      infarct size in patients and ex vivo. METHODS: Twenty-six patients with previous
      myocardial infarction who underwent a CMR scan were included. Images were
      acquired 10-20 minutes after an injection of 0.2 mmol/kg gadolinium-based
      contrast agent. Two LGE-sequences, 3D-inversion recovery (IR) and 2D-phase
      sensitive (PS) IR, were used in all patients to quantify infarction size.
      Furthermore, six pigs with reperfused infarction in the left anterior descending
      artery (40 minutes occlusion and 4 hours of reperfusion) were scanned with 2D-
      and 3D-LGE ex vivo. A high resolution T1-sequence was used as reference for the
      infarct quantification ex vivo. Spearman's rank-order correlation, Wilcoxon
      matched pairs test and bias according to Bland-Altman was used for comparison of
      infarct size with different LGE-sequences. RESULTS: There was no significant
      difference between the 2D- and 3D-LGE sequence in left ventricular mass (LVM)
      (2D: 115 +/- 25 g; 3D: 117 +/- 24 g: p = 0.35). Infarct size in vivo using 2D-
      and 3D-LGE showed high correlation and low bias for both LGE-sequences both in
      absolute volume of infarct (r = 0.97, bias 0.47 +/- 2.1 ml) and infarct size as
      part of LVM (r = 0.94, bias 0.16 +/- 2.0%). The 2D- and 3D-LGE-sequences ex vivo
      correlated well (r = 0.93, bias 0.67 +/- 2.4%) for infarct size as part of the
      LVM. The IR LGE-sequences overestimated infarct size as part of the LVM ex vivo
      compared to the high resolution T1-sequence (bias 6.7 +/- 3.0%, 7.3 +/- 2.7% for
      2D-PSIR and 3D-IR respectively, p < 0.05 for both). CONCLUSIONS: Infarct
      quantification with 2D- and 3D-LGE gives similar results in vivo with a very low
      bias. IR LGE-sequences optimized for in vivo use yield an overestimation of
      infarct size when used ex vivo.

PMID- 24308674
TI  - Pathophysiology and recent findings of primary biliary cirrhosis complicated by
      systemic sclerosis.
AB  - Primary biliary cirrhosis (PBC) can be complicated by systemic sclerosis (SSc)
      and, more specifically, limited cutaneous SSc (lcSSc), which was previously
      called CREST syndrome. Moreover, combined PBC and SSc has been described in many
      case reports. Although neither the etiology of PBC nor that of SSc has been
      elucidated, some genetic and immunological factors are known to be shared. Both
      disorders are autoimmune fibrotic diseases characterized by increased levels of
      profibrotic cytokines transforming growth factor beta (TGFbeta) and interleukin
      6, which have recently been suggested to influence T-helper 17 cells and
      regulatory T cells involved in acquired immunity. lcSSc is accompanied by CREST
      symptoms, although complete CREST cases are rare, with relatively high prevalence
      of Raynaud's phenomenon, sclerodactyly and telangiectasia, and lower prevalence
      of calcinosis and esophageal dysmotility. Because patients with anticentromere
      antibody positive PBC-SSc are at a high risk of developing portal hypertension,
      particular attention should be paid to the management of gastroesophageal
      varices. In addition, the management of SSc-related non-hepatic disorders, such
      as pulmonary fibrosis, pulmonary hypertension, heart disorder, infection and
      malignancy, is also important for improved outcomes. Because PBC is often
      complicated by rheumatic disease, hepatologists should keep the possibility of
      systemic disorder in mind when examining PBC patients. 

PMID- 24308676
TI  - The effects of beta-alanine supplementation on physical working capacity at heart
      rate threshold.
AB  - Beta-alanine (BA) supplementation has been shown to delay neuromuscular fatigue
      as a result of increased muscle carnosine concentrations. Carnosine has also been
      found in brain and cardiac tissue. The physical working capacity test at heart
      rate threshold (PWC(HRT)) is a global estimate of the onset of fatigue during
      exercise, influenced by central and peripheral factors. The purpose of this study
      was to determine the effects of 28 days of BA supplementation on the PWC(HRT).
      Thirty subjects (mean +/- SD; age: 21.0 +/- 2.1 years; body mass: 72.7 +/- 14.5
      kg; height: 170.1 +/- 7.9 cm) were randomly assigned to BA (n = 15) or placebo
      (PL, n = 15) groups. Testing included eight to nine total visits: an enrolment
      day, physical screening, peak oxygen consumption (V(.)O(2peak)) and two PWC(HRT)
      assessments over 4 days. Significant differences existed between BA and PL for
      PWC(HRT) (P = 0.001; mean?: BA? = +24.2 watts, PL? = +11.2 watts), but not for
      V(.)O(2peak) (P = 0.222), time to exhaustion (TTE; P = 0.562) or ventilatory
      threshold (VT; P = 0.134). Results suggest that BA may increase heart rate
      training threshold. These results, in combination with one previous study
      reporting a potential effect of BA on HR, suggest that future studies should
      evaluate both central and peripheral aspects of fatigue with BA intake.

PMID- 24308675
TI  - Phenylspirodrimanes with anti-HIV activity from the sponge-derived fungus
      Stachybotrys chartarum MXH-X73.
AB  - Seven new phenylspirodrimanes, named stachybotrins D-F (1, 3, 4), stachybocins E
      and F (5, 6), and stachybosides A and B (7, 8), and four known compounds (2, 9
      11), were isolated from the sponge-derived fungus Stachybotrys chartarum MXH-X73.
      Their structures were determined by detailed analysis of spectroscopic data. The
      absolute configurations of 1-8 were determined by chemical hydrolysis and
      modified Mosher's and Marfey's methods. All compounds were tested in an anti-HIV
      activity assay, and compound 1 showed an inhibitory effect on HIV-1 replication
      by targeting reverse transcriptase. Further study exhibited that 1 could block
      NNRTIs-resistant strains (HIV-1RT-K103N, HIV-1RT-L100I,K103N, HIV-1RT
      K103N,V108I, HIV-1RT-K103N,G190A, and HIV-1RT-K103N,P225H) as well as wild-type
      HIV-1 (HIV-1wt) with EC50 values of 7.0, 23.8, 13.3, 14.2, 6.2, and 8.4 MUM,
      respectively. 

PMID- 24308677
TI  - Measuring individual vulnerability to sleep loss--the CHICa scale.
AB  - The aim of this project was to construct a psychometrically satisfying scale to
      describe subjective reactions to sleep deprivation. First, on the basis of a
      literature review, a list of items was generated which reflected the negatively
      affected mood and reduced wellbeing associated with sleep loss. Additionally,
      psychology students were asked to describe their cognitive and emotional symptoms
      following a night with curtailed sleep. As a result, 69 items were included in
      the experimental set. University students (n = 102, females, mean age 22.5 +/-
      1.9 years) completed the form several times during 1 week in June (while
      preparing for examinations) and on a free day in September; a total of 460 forms
      were collected. The final, 26-item version of the scale was validated in a sleep
      deficit experiment lasting 1 week, conducted with 25 female participants (mean
      age 23.4 +/- 1.9 years). Factor analysis showed 71.7% of total variance explained
      by four components: impaired thermoregulation (C for cold), disrupted appetite (H
      for hunger), affective problems (I for irritability) and lowered level of
      cognitive functioning (Ca for cognitive attenuation). A Polish version of the
      CHICa scale showed satisfactory psychometric properties. Cronbach's alpha of the
      subscales were between 0.90 and 0.95. All four subscales exhibited a significant
      increase with an experimental 3-h daily sleep restriction over a period of 1
      week; cognitive attenuation was the most symptomatic. Cognitive problems (reduced
      concentration, comprehension and accuracy) and a lack of energy seem to be the
      most specific subjective manifestations of the chronic sleep deficit state. CHICa
      may be helpful in research on inter-and intra-individual differences and on the
      efficacy of various counteractive treatments for the consequences of sleep
      deprivation. 

PMID- 24308678
TI  - The role of systemic and targeted therapies in brain metastases.
AB  - For many years, brain metastases (BMs) have been considered as the final stage of
      a disease course and engendered skepticism about the efficacy of treatments.
      Local treatments, mainly, whole-brain radiotherapy have been the standard of
      care, whereas chemotherapy has been considered of limited efficacy due to the
      potential role of blood-brain barrier. 

PMID- 24308679
TI  - Prostate stem cell antigen and cancer risk, mechanisms and therapeutic
      implications.
AB  - Prostate stem cell antigen (PSCA) was originally identified as a tumor antigen in
      prostate cancer. Recent studies indicated that PSCA was correlated with many
      cancer types. In this review, we will consider the origin of PSCA, discuss the
      expression of PSCA in normal and cancer tissue, describe PSCA polymorphisms and
      cancer risk, summarize potential mechanisms for PSCA involvement in cancer; and
      look into the therapeutic implications of PSCA. PSCA is upregulated in prostate
      cancer, pancreatic cancer and bladder cancer, as well as a number of others,
      making it an ideal clinical target for both diagnosis and therapy. Future studies
      will be required to explore its mechanisms on various cancer types, and to
      confirm its clinical utility for diagnosis and immunotherapy strategies. The
      study of PSCA regulation and expression may also provide information on normal
      prostate development and prostate carcinogenesis. 

PMID- 24308680
TI  - Review of management issues in relapsed osteosarcoma.
AB  - Osteosarcoma is the most common primary malignant bone tumor in children and
      adolescents. With combined modality treatment long-term survival rate for
      localized disease is near 70%. Thirty percent of patients relapse with lung as
      the commonest site. Surgery is the treatment of choice for relapsed patients
      whenever possible. Addition of chemotherapy to surgery provides survival benefit
      in patients not achieving second surgical remission. Even patients with multiple
      lung recurrences can be cured with repeated thoracotomies. Disease-free interval
      and complete surgical resection are the main prognostic factor for post-relapse
      survival. 

PMID- 24308681
TI  - The current position and the future perspectives of cervical cancer screening.
AB  - Cervical screening programs for detecting cancer and precancer have dramatically
      reduced the incidence and mortality rates of cervical cancer since the 1960s. The
      efficacy of the screening programs depends on participation and the accuracy of
      the screening tests. Unfortunately, the participation rates are suboptimal; more
      than half the women with cervical cancer have not or have only sporadically been
      screened. Increasing participation is the best way of maximizing the program's
      benefit. Furthermore, cytology screening lacks high sensitivity for high-grade
      cervical intraepithelial neoplasia (>=CIN2). High-risk human papillomavirus
      (hrHPV) screening is more sensitive in the detection of cervical intraepithelial
      neoplasia than cytology screening, but less specific, so that additional triage
      testing is still mandatory. The aim of this article is to reflect on the efficacy
      of current cervical cancer screening and on promising future screening strategies
      with primary hrHPV testing and additional triage strategies for hrHPV-positive
      screening results. 

PMID- 24308682
TI  - Family history and the risk of cancer: genetic factors influencing multiple
      cancer sites.
AB  - A number of co-aggregations of cancers at different sites has been reported,
      including recognized syndromes (e.g., Li-Fraumeni), and aggregations between
      cancers at breast, stomach and ovary, between cancers at prostate, urinary tract
      and other sites, as well as between several tobacco-related neoplasms. In a
      network of case-control studies from Italy and Switzerland, including more than
      12,000 cases of 13 different cancers, after controlling for multiple testing,
      significant associations emerged between oral and pharyngeal cancer and family
      history of laryngeal cancer (relative risk (RR): 3.3); esophageal cancer and
      family history of oral and pharyngeal cancer RR: 4.1; breast cancer and family
      history of colorectal cancer (RR: 1.5) and of hemolymphopoietic cancers (RR:
      1.7); ovarian cancer and family history of breast cancer (RR: 2.3); and prostate
      cancer and family history of bladder cancer (RR: 3.4). Shared exposures to
      environmental factors within families account for some of the observed
      aggregations, together with heritable, and hence, genetic factors. 

PMID- 24308683
TI  - Brain metastases in breast cancer.
AB  - Despite therapeutic advances, the development of breast cancer brain metastases
      (BCBM) is still the harbinger of a dismal prognosis. Patient outcomes vary
      depending on factors, including tumor phenotype, extent of disease within and
      outside the brain, as well as patient performance status. Treatment includes
      surgery, radiation therapy and systemic therapy determined by patient and tumor
      characteristics. Despite these approaches, novel treatments are needed and there
      is growing interest in systemic therapies. However, the efficacy of pharmacologic
      agents is hampered by poor penetration of drugs across the blood-brain barrier.
      Therefore, there is a pressing need for a greater understanding of the natural
      history of BCBM to guide the development of further therapies. This review
      analyzes prognosis and treatment of BCBM by tumor phenotype and discusses ongoing
      research into new therapies. 

PMID- 24308684
TI  - Management of patients with metastasis to the vertebrae: recommendations from the
      Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group.
AB  - The purpose of this article is to outline the current approach to patients
      affected by metastasis to the spine and to present a clinical and surgical
      algorithm available for clinicians and for future research. A modern approach to
      the patients affected by spinal metastasis in fact requires a multidisciplinary
      contest where oncologists, radiotherapists, surgeons and physical therapists
      cooperate with shared vision to provide the best possible integrated treatments
      available. The authors of this article constitute the Bone Metastasis Study Group
      of the Italian Orthopaedic Society (SIOT): a national group of orthopedic tumor
      surgeons who are dedicated to studying the approach, techniques and outcomes of
      surgery for metastatic tumors of the musculoskeletal system. 

PMID- 24308685
TI  - Optimal management of elderly patients with myeloma.
AB  - Many advances have been made in the treatment of patients with multiple myeloma
      including elderly subjects. The introduction of novel agents, such as
      thalidomide, lenalidomide, bortezomib, have revolutionized the treatment paradigm
      of this neoplasm, and second-generation molecules are currently being tested to
      offer patients a wider variety of treatment options and to improve outcome. The
      efficacy of a regimen should be carefully balanced against its toxicity profile.
      Elderly patients are particularly susceptible to adverse events that may lead to
      early treatment discontinuation. Thus, a more accurate distinction within the
      elderly population and a more appropriate treatment allocation is necessary. Here
      we describe the major and more recent treatment options available today for
      elderly patients with multiple myeloma. 

PMID- 24308686
TI  - Prior exposure to chemotherapy: a marker of sensitivity and selection for
      antiangiogenic therapy in breast cancer?
AB  - The identification of patients who are more likely to derive benefit from
      antiangiogenic therapy is a key to refine patient selection and so maximize
      clinical benefit, and reduce unnecessary treatment costs. Improved patient
      selection will equally be effective in minimizing the exposure of non-eligible
      patients to ineffectual treatment which could be associated with adverse effects
      as well as delaying effective treatment. Herein, we review the literature from
      clinical trials suggesting that the addition of antiangiogenic agents to
      chemotherapy for the treatment of HER-2 negative metastatic breast cancer in
      patients previously exposed to chemotherapy may deliver differential therapeutic
      benefit and may serve as a selection criteria in the current absence of a robust
      biomarker. 

PMID- 24308687
TI  - Biopsy is contraindicated in the management of penile calciphylaxis.
AB  - INTRODUCTION: Calciphylaxis, a rare obliterative small vessel vasculopathy
      associated with diabetes mellitus (DM), end-stage renal disease (ESRD), portends
      a poor prognosis. Because penile involvement is rare, agreement on appropriate
      diagnosis and management is unclear. AIM: To determine the role and effect of
      penile biopsy for diagnosis and management of penile calciphylaxis. METHODS:
      Medical records of three penile calciphylaxis patients from our institution were
      evaluated. Data collected included age, history of DM, ESRD, and hemodialysis
      (HD) status, serum calcium (Ca), Ca * phosphorous product (C * P), parathyroid
      hormone (PTH), performance of biopsy, presence of non-penile cutaneous lesions,
      intervention, survival, and time from diagnosis to death. PubMed Search for
      relevant publications from 1995 to 2012 was performed to identify case reports of
      penile calciphylaxis that provided the same clinical data obtained from the 3
      patients from our institution. MAIN OUTCOME MEASURES: Clinical evidence for
      outcomes in patients with penile calciphylaxis after biopsy of penile lesion
      compared to those without biopsy. RESULTS: A total of sixteen patients were
      identified in the literature and in our institution with clinical data of
      interest. Overall, 10/16 (62.5%) patients identified with penile calciphylaxis
      had a penile biopsy, and 7/10 (70%) experienced disease progression, while only
      3/10 (30%) stabilized. Mean time to death in this patient population was short,
      approximately 6.5 months, regardless of type of intervention. CONCLUSION: Based
      on the results of our study, we argue that conservative measures should be
      employed as first line therapy for penile calciphylaxis. More importantly,
      secondary to likely resultant progression of necrosis, penile biopsy is not only
      unnecessary for diagnosis of penile calciphylaxis, but is also harmful and
      contraindicated.

PMID- 24308688
TI  - The development and validation of a patient-reported quality of life measure for
      people with mild cognitive impairment.
AB  - BACKGROUND: No validated patient-reported outcome measure (PROM) exists
      specifically to assess quality of life in mild cognitive impairment (MCI); we
      report a study conducted to develop such a measure. METHODS: Semi-structured in
      depth interviews were carried out with 23 people with MCI in order to determine
      items for a draft questionnaire. These interviews were audio-recorded,
      transcribed, and content analyzed. The draft questionnaire was refined following
      feedback from a focus group. 280 questionnaires were posted to subjects recruited
      from memory clinics and research databases, the response rate was 56% i.e. 146
      questionnaires were included in the final analysis. The completed questionnaires
      were analyzed using factor analytic techniques to produce the final measure;
      construct validity was assessed by correlation with a generic patient-reported
      outcome measure, the SF-12v2. RESULTS: Factor analysis produced a 13-item measure
      tapping two domains of patient-reported quality of life ("Emotional Effects" and
      "Practical Concerns"). Internal consistency reliability was high for both domains
      (alpha was 0.91 and 0.85 respectively). Both dimensions were highly and
      significantly correlated with the Mental Component Summary score of the SF-12v2
      ("emotional effects" rho = -0.43, p < 0.001 and "practical concerns" rho = -0.56,
      p < 0.001). CONCLUSIONS: The Mild Cognitive Impairment Questionnaire (MCQ) is a
      13-item measure developed specifically to measure patient-reported outcomes in
      people with MCI. It was created on the basis of patient report and has been shown
      to have good psychometric properties. It is likely to prove valuable in the
      evaluation of treatment regimes in this patient group.

PMID- 24308689
TI  - Nanopore integrated nanogaps for DNA detection.
AB  - A high-throughput fabrication of sub-10 nm nanogap electrodes combined with solid
      state nanopores is described. These devices should allow concomitant tunneling
      and ionic current detection of translocating DNA molecules. We report the optimal
      fabrication parameters in terms of dose, resist thickness, and gap shape that
      allow easy reproduction of the fabrication process at wafer scale. The device
      noise and current voltage characterizations performed and the influence of the
      nanoelectrodes on the ionic current noise is identified. In some cases, ionic
      current rectification for connected or biased nanogap electrodes is also
      observed. In order to increase the extremely low translocation rates, several
      experimental strategies were tested and modeled using finite element analysis.
      Our findings are useful for future device designs of nanopore integrated
      electrodes for DNA sequencing. 

PMID- 24308690
TI  - Stormwater dissolved organic matter: influence of land cover and environmental
      factors.
AB  - Dissolved organic matter (DOM) plays a major role in defining biological systems
      and it influences the fate and transport of many pollutants. Despite the
      importance of DOM, understanding of how environmental and anthropogenic factors
      influence its composition and characteristics is limited. This study focuses on
      DOM exported as stormwater from suburban and urban sources. Runoff was collected
      before entering surface waters and DOM was characterized using specific
      ultraviolet absorbance at 280 nm (a proxy for aromaticity), molecular weight,
      polydispersity and the fraction of DOM removed from solution via hydrophobic and
      H-bonding mechanisms. General linear models (GLMs) incorporating land cover,
      precipitation, solar radiation and selected aqueous chemical measurements
      explained variations in DOM properties. Results show (1) molecular
      characteristics of DOM differ as a function of land cover, (2) DOM produced by
      forested land is significantly different from other landscapes, particularly
      urban and suburban areas, and (3) DOM from land cover that contains paved
      surfaces and sewers is more hydrophobic than from other types of land cover. GLMs
      incorporating environmental factors and land cover accounted for up to 86% of the
      variability observed in DOM characteristics. Significant variables (p < 0.05)
      included solar radiation, water temperature and water conductivity. 

PMID- 24308692
TI  - Low expression of basic fibroblastic growth factor in mesenchymal stem cells and
      bone marrow of children with aplastic anemia.
AB  - BACKGROUND: Our previous experiments with gene chip suggested that basic
      fibroblastic growth factor (FGF2) levels were lower in mesenchymal stem cell
      (MSC) from aplastic anemia patients. The purpose of this study was to determine
      the expression of FGF2 in MSC and in bone marrow of children with aplastic anemia
      to better understand the role of low FGF2 expression in the pathogenesis of
      aplastic anemia. PROCEDURE: MSCs from the bone marrow of aplastic anemia children
      and control group were cultured in vitro. Growth curves of primary and passage
      MSC were plotted. FGF2 gene expression in MSCs was detected using quantitative
      real-time polymerase chain reaction (RT-PCR). FGF2 protein expression in
      mononuclear cells and FGF2 protein level in extracellular fluid of bone marrow
      were also investigated. RESULT: Decreased growth of MSCs from aplastic anemia
      children was observed after passage 8 in serial subcultivation, and FGF2 gene
      expression was downregulated. Within the patients' bone marrow, low FGF2
      expression was validated both in mononuclear cells and in the extracellular
      fluid. CONCLUSION: Low FGF2 gene expression in MSCs and low FGF2 protein level in
      bone marrow of aplastic anemia may involve to pathogenesis of aplastic anemia.

PMID- 24308691
TI  - Genetic diversity and structure in Leishmania infantum populations from
      southeastern Europe revealed by microsatellite analysis.
AB  - BACKGROUND: The dynamic re-emergence of visceral leishmaniasis (VL) in south
      Europe and the northward shift to Leishmania-free European countries are well
      documented. However, the epidemiology of VL due to Leishmania infantum in
      southeastern (SE) Europe and the Balkans is inadequately examined. Herein, we aim
      to re-evaluate and compare the population structure of L. infantum in SE and
      southwestern (SW) Europe. METHODS: Leishmania strains collected from humans and
      canines in Turkey, Cyprus, Bulgaria, Greece, Albania and Croatia, were
      characterized by the K26-PCR assay and multilocus enzyme electrophoresis (MLEE).
      Genetic diversity was assessed by multilocus microsatellite typing (MLMT) and MLM
      Types were analyzed by model- and distance- based algorithms to infer the
      population structure of 128 L. infantum strains. RESULTS: L. infantum MON-1 was
      found predominant in SE Europe, whilst 16.8% of strains were MON-98. Distinct
      genetic populations revealed clear differentiation between SE and SW European
      strains. Interestingly, Cypriot canine isolates were genetically isolated and
      formed a monophyletic group, suggesting the constitution of a clonal MON-1
      population circulating among dogs. In contrast, two highly heterogeneous
      populations enclosed all MON-1 and MON-98 strains from the other SE European
      countries. Structure sub-clustering, phylogenetic and Splitstree analysis also
      revealed two distinct Croatian subpopulations. A mosaic of evolutionary effects
      resulted in consecutive sub-structuring, which indicated substantial
      differentiation and gene flow among strains of both zymodemes. CONCLUSIONS: This
      is the first population genetic study of L. infantum in SE Europe and the
      Balkans. Our findings demonstrate the differentiation between SE and SW European
      strains; revealing the partition of Croatian strains between these populations
      and the genetic isolation of Cypriot strains. This mirrors the geographic
      position of Croatia located in central Europe and the natural isolation of the
      island of Cyprus. We have analysed the largest number of MON-98 strains so far.
      Our results indicate extensive gene flow, recombination and no differentiation
      between MON-1 and MON-98 zymodemes. No correlation either to host specificity or
      place and year of strain isolation was identified. Our findings may be associated
      with intensive host migration and common eco-epidemiological characteristics in
      these countries and give valuable insight into the dynamics of VL.

PMID- 24308694
TI  - Autonomous technology - sources of confusion: a model for explanation and
      prediction of conceptual shifts.
AB  - Today, autonomous is often used for technology with a more intelligent self
      management capability than common automation. This concept usage is maladaptive,
      ignoring both the distinction between autonomy and heteronomy according to Kant's
      categorical imperative and that the meaning of autonomy implies qualities
      technology cannot have. Being autonomous is about having the right to be wrong, a
      right justified by accountability and insightful understanding of real-life
      values, and it is about being externally uncontrollable. The contemporary use of
      autonomy as well as similar concepts is discussed and a model is presented
      showing how six sources of confusion interact in a vicious circle that impede
      human authority and autonomy. Our goal is to sort out these confusions and
      contribute to a development in which the different roles of machines and people,
      and human responsibilities, are explicated rather than blurred, which should
      facilitate the forming of truly beneficial and complementary systems. 

PMID- 24308693
TI  - Safety of Porcine Reproductive and Respiratory Syndrome Modified Live Virus (MLV)
      vaccine strains in a young pig infection model.
AB  - The objective of this study was to compare the safety of all modified live virus
      vaccines commercially available in Europe against Porcine Reproductive and
      Respiratory Syndrome Virus (PRRSV) under the same experimental conditions. For
      this purpose, one hundred and twenty three-week-old piglets, divided into five
      groups, were used. On day 0 of the experiment, nine pigs per group were removed
      and the remaining fifteen were vaccinated with the commercial vaccines Ingelvac
      PRRS MLV, Amervac PRRS, Pyrsvac-183 and Porcilis PRRS by the IM route or were
      mock vaccinated and used as controls. On day 3, the nine unvaccinated pigs were
      re-introduced into their respective groups and served as sentinel pigs. Clinical
      signs were recorded daily and lung lesions were determined on days 7, 14 and 21,
      when 5 vaccinated pigs per group were euthanized. Blood samples and swabs were
      taken every three days and different organs were collected at necropsy to
      determine the presence of PRRSV. None of the vaccines studied caused detectable
      clinical signs in vaccinated pigs although lung lesions were found. Altogether,
      these results indicate that all vaccines can be considered clinically safe.
      However, some differences were found in virological parameters. Thus, neither
      Pyrsvac-183 nor Porcilis PRRS could be detected in porcine alveolar macrophage
      (PAM) cultures or in lung sections used to determine PRRSV by
      immunohistochemistry, indicating that these viruses might have lost their ability
      to replicate in PAM. This inability to replicate in PAM might be related to the
      lower transmission rate and the delay in the onset of viremia observed in these
      groups. 

PMID- 24308695
TI  - Atomistic insight into the minimum wear depth of Cu(111) surface.
AB  - In the present work, we investigate the minimum wear depth of single crystalline
      Cu(111) under single asperity friction by means of molecular dynamics
      simulations. The atomistic mechanisms governing the incipient plasticity are
      elucidated by characterizing specific defect structures and are correlated to the
      observed mechanical and frictional responses of the material. Furthermore, the
      effect of probe radius on the friction process is studied. Our simulations
      indicate that the formation of wear impression is closely associated with defect
      nucleation and the minimum wear depth is equivalent to the critical penetration
      depth at which plasticity initiates. It is found that the probe radius has a
      strong influence on the formation of defect structures and the observed
      mechanical responses. 

PMID- 24308696
TI  - Cells of Langerhans cell histiocytosis and epidermal Langerhans cells differ
      under reflectance confocal microscopy: first observation.

PMID- 24308697
TI  - Is paediatric trauma severity overestimated at triage? An observational follow-up
      study.
AB  - BACKGROUND: Severe paediatric trauma is rare, and pre-hospital and local hospital
      personnel experience with injured children is often limited. We hypothesised that
      a higher proportion of paediatric trauma victims were taken to the regional
      trauma centre (TC). METHODS: This is an observational follow-up study that
      involves one level I TC and seven local hospitals. We included paediatric (< 16
      years) and adult (>= 16-<= 79 years) trauma patients with a driving distance to
      the TC > 30 minutes. The primary end-point was the proportion of trauma patients
      arriving in the TC. RESULTS: We included 1934 trauma patients, 238 children and
      1696 adults. A total of 33/238 children (13.9%) vs. 304/1696 adults (17.9%) were
      transported to the TC post-injury (P = 0.14). Among these, children were
      significantly less injured than adults [median Injury Severity Score (ISS) 9 vs.
      14, P < 0.01]. There was no significant difference between the groups in the
      proportion of seriously injured trauma victims (ISS > 15) taken to the TC [8/11
      (72.7%) vs. 139/182 (76.4%)]. The corresponding figures for ISS < 15 were 25/227
      (11.0%) and 164/1509 (10.9%), respectively. No significant difference was found
      in intensive care unit length of stay or time to TC arrival. No paediatric vs.
      36/1671 (2.2%) adult deaths were observed at 30-day follow-up (P = 0.03).
      CONCLUSIONS: There was no difference in the proportion of paediatric and adult
      trauma patients transported to the TC, neither overall nor among severely injured
      patients. Paediatric trauma patients admitted to the TC were, however,
      significantly less injured than adults.

PMID- 24308698
TI  - Food intake increases liver stiffness measurements and hampers reliable values in
      patients with chronic hepatitis B and healthy controls: the PROLIFICA experience
      in The Gambia.
AB  - BACKGROUND: By increasing the hepatic blood circulation, food intake has been
      suggested to increase liver stiffness measurement (LSM) values in HCV-infected
      patients. AIM: To investigate prospectively the effects of food intake on LSM in
      hepatitis B virus (HBV)-infected patients and healthy controls. METHODS: In The
      Gambia, patients included in the PROLIFICA project are screened for HBV at the
      community level and then invited for fasting assessment including LSM. Between
      April 2012 and October 2012, each day, the first five participants were invited
      to participate in this study. After the initial examination, a standardised 850
      Kcal breakfast was provided. Effect of food intake was assessed by examining mean
      difference of LSM, IQR and IQR/LSM at T0 (fasting LSM1), T30min (LSM2) and
      T120min (LSM3) respectively. RESULTS: A total of 209 subjects were enrolled in
      this study (133 were HBV positive, 76 healthy controls). Unreliable measurements
      occurred more frequently after food intake (5%, 24% and 18% at T0, T30min and
      T120min respectively). In both groups, median LSM2 was significantly higher than
      LSM1 [6.2 (IQR: 5.4, 7.9)] vs. 4.9 (4.2, 6.2), P < 0.0001. LSM3 was still higher
      than the baseline, but lower than LSM2. In multivariable analysis, no factor
      modified the effect of breakfast on LSM. In a subgroup of patients having liver
      biopsies, we confirmed that food intake can overestimate liver fibrosis.
      CONCLUSIONS: Food intake significantly increases liver stiffness measurement and
      its IQR values in patients with chronic hepatitis B as well as healthy
      individuals; and also the number of unreliable liver stiffness measurement
      values.

PMID- 24308699
TI  - Aptamer-based sensing platform using three-way DNA junction-driven strand
      displacement and its application in DNA logic circuit.
AB  - We proposed a new three-way DNA junction-driven strand displacement mode and
      fabricated an aptamer-based label-free fluorescent sensing platform on the basis
      of this mechanism. Assembling the aptamer sequence into the three-way DNA
      junction makes the platform sensitive to the target of the aptamer. A label-free
      signal readout method, split G-quadruplex enhanced fluorescence of protoporphyrin
      IX (PPIX), was used to report the final signal. Here, adenosine triphosphatase
      (ATP) was taken as a model and detected through this approach, and DNA strand
      could also be detected by it. The mechanism was investigated by native
      polyacrylamide gel electrophoresis. Furthermore, on the basis of this molecular
      platform, we built a logic circuit with ATP and DNA strands as input. Aptamer
      played an important role in mediating the small molecule ATP to tune the DNA
      logic gate. Through altering the aptamer sequence, this molecular platform will
      be sensitive to various stimuli and applied in a wide field. 

PMID- 24308700
TI  - Using the Bernoulli trial approaches for detecting ordered alternatives.
AB  - BACKGROUND: Diagnostic problems in clinical trials are sometimes ordinal. For
      example, colon tumor staging was performed according to the TNM classification.
      However, clinical data are limited by markedly small sample sizes in some stage.
      METHODS: We propose a distribution-free test for detecting ordered alternatives
      in a completely randomized design. The new statistic is based on summing all
      correctly (ascending) ordered samples. RESULTS: The exact mean and variance of
      the null distribution are derived and it is shown that this distribution is
      asymptotically normal. Furthermore, we show using Monte Carlo simulation that the
      proposed test is a significant improvement over the Terpstra-Magel test. That is,
      power is decreased where the investigator falsely assumes an a priori ordering
      relationship. CONCLUSIONS: We conclude that these tests frequently detect an
      ordered trend when, in fact, one does not exist. However, the new test can reduce
      the error rate, at least not to the extent in which the Jonckheere-Terpstra test
      does.

PMID- 24308701
TI  - Do stage-specific functional responses of consumers dampen the effects of
      subsidies on trophic cascades in streams?
AB  - Resource subsidies often weaken trophic cascades in recipient communities via
      consumers' functional response to the subsidies. Consumer populations are
      commonly stage-structured and may respond to the subsidies differently among the
      stages yet less is known about how this might impact the subsidy effects on the
      strength of trophic cascades in recipient systems. We show here, using a large
      scale field experiment, that the stage structure of a recipient consumer would
      dampen the effects of terrestrial invertebrate subsidies on the strength of
      trophic cascade in streams. When a high input rate of the terrestrial
      invertebrates was available, both large and small fish stages switched their diet
      to the terrestrial subsidy, which weakened the trophic cascade in streams.
      However, when the input rate of the terrestrial invertebrates was at a moderate
      level, the terrestrial subsidy did not weaken the trophic cascade. This
      discrepancy was likely due to small fish stages being competitively excluded from
      feeding on the subsidy by larger stages of fish and primarily foraging on benthic
      invertebrates under the moderate input level. Although previous studies using
      single fish stages have clearly demonstrated that the terrestrial invertebrate
      input equivalent to our moderate input rate weakened the trophic cascade in
      streams, this subsidy effect might be overestimated given small fish stage may
      not switch their diet to the subsidy under competition with large fish stage.
      Given the ubiquity of consumer stage structure and interaction among consumer
      stages, the effects we saw might be widespread in nature, requiring future
      studies that explicitly involve consumer's stage structure into community
      ecology. 

PMID- 24308705
TI  - Subjective memory complaints, depressive symptoms and cognition in patients
      attending a memory outpatient clinic.
AB  - BACKGROUND: The goals of this study were to establish prevalence of subjective
      memory complaints (SMC) and depressive symptoms (DS) and their relation to
      cognitive functioning and cognitive status in an outpatient memory clinic cohort.
      METHODS: Two hundred forty-eight cognitively healthy controls and 581 consecutive
      patients with cognitive complaints who fulfilled the inclusion criteria were
      included in the study. RESULTS: A statistically significant difference (p <
      0.001) between control group and patient group regarding mean SMC was detected.
      7.7% of controls reported a considerable degree of SMC, whereas 35.8% of patients
      reported considerable SMC. Additionally, a statistically significant difference
      (p < 0.001) between controls and patient group regarding Beck depression score
      was detected. 16.6% of controls showed a clinical relevant degree of DS, whereas
      48.5% of patients showed DS. An analysis of variance revealed a statistically
      significant difference across all four groups (control group, SCI group, naMCI
      group, aMCI group) (p < 0.001). Whereas 8% of controls reported a considerable
      degree of SMC, 34% of the SCI group, 31% of the naMCI group, and 54% of the aMCI
      group reported considerable SMC. A two-factor analysis of variance with the
      factors cognitive status (controls, SCI group, naMCI group, aMCI group) and
      depressive status (depressed vs. not depressed) and SMC as dependent variable
      revealed that both factors were significant (p < 0.001), whereas the interaction
      was not (p = 0.820). CONCLUSIONS: A large proportion of patients seeking help in
      a memory outpatient clinic report considerable SMC, with an increasing degree
      from cognitively healthy elderly to aMCI. Depressive status increases SMC
      consistently across groups with different cognitive status.

PMID- 24308702
TI  - Extracellular ubiquitin increases expression of angiogenic molecules and
      stimulates angiogenesis in cardiac microvascular endothelial cells.
AB  - Extracellular Ub is an immune modulator that plays a role in suppression of
      inflammation, organ injury, myocyte apoptosis, and fibrosis. The purpose of this
      study was to investigate the effects of extracellular Ub on the process of
      cardiac angiogenesis. CMECs and aortic tissue were isolated from rats to measure
      changes in angiogenic protein levels and to assess angiogenic responses to
      extracellular Ub. In CMECs, extracellular Ub increased protein levels of VEGF-A
      and MMP-2, known angiogenesis regulators. CMECs demonstrated enhanced
      rearrangement of fibrillar actin and migration in response to Ub treatment. Ub
      treated CMECs demonstrated an increase in tube network formation which was
      inhibited by the CXCR4 receptor antagonist, AMD3100. Methylated Ub, unable to
      form polyubiquitin chains, enhanced tube network formation. Aortic ring sprouting
      assays demonstrated that Ub increases microvessel sprouting in the Matrigel. The
      results of our study suggest a novel role for extracellular Ub in cardiac
      angiogenesis, providing evidence that extracellular Ub, at least in part acting
      via the CXCR4 receptor, has the potential to facilitate the process of
      angiogenesis in myocardial endothelial cells.

PMID- 24308704
TI  - Role of immunohistochemistry for hepatitis D and hepatitis B virus in hepatitis
      delta.
AB  - BACKGROUND & AIMS: Immunohistochemical assessment of liver tissue in chronic
      delta hepatitis (CDH) is underinvestigated. Aim of the study was (i) to assess
      variables associated with hepatitis D antigen (HDAg), hepatitis B surface antigen
      (HBsAg) and hepatitis B core antigen (HBcAg) staining in the liver. METHODS:
      Demographic, biochemical and virologic data collected from the HIDIT 1 study were
      used. HBsAg, HBcAg and HDAg immunohistochemical (IHC) staining was
      semiquantitatively assessed. RESULTS: Hepatitis D antigen immunohistochemical
      staining displayed positive correlations with age and alanine aminotransferase
      (ALT) and negative correlations with serum HBsAg (P = 0.01 for all). HBsAg IHC
      displayed a negative correlation with gamma glutamyl transferase and positive
      correlations with serum HBV DNA, serum HBsAg levels and HBeAg serology (P <
      0.001, P = 0.02 and P = 0.007 respectively). HBcAg staining was mainly nuclear
      and displayed negative correlations with serum HBsAg and histologic activity (P =
      0.002 and P = 0.02 respectively). Pegylated IFN based treatment led to a decline
      of all IHC markers, however, these markers had no impact on treatment outcome.
      CONCLUSIONS: These data suggest an association of liver injury with HDAg
      expression in CDH whereas the negative correlation between HBcAg expression and
      liver injury and the overall nuclear localization of HBcAg suggest that HBcAg
      does not contribute to liver injury in CDH. HDV cases with high level of HBV
      replication, high serum HBsAg levels, HBeAg positivity, that are probably in the
      earlier stages of disease (low gamma-glutamyl transferase), had a more intense
      HBsAg staining profile. Overall, the data enforce the importance of HDAg and
      HBsAg in different phases of CDH infection.

PMID- 24308706
TI  - Gait pattern in 9-11-year-old children with generalized joint hypermobility
      compared with controls; a cross-sectional study.
AB  - BACKGROUND: To study differences in gait patterns in 10-year-old children with
      Generalized Joint Hypermobility (GJH) and with no GJH (NGJH). METHODS: A total of
      37 children participated (19 GJH, 18 NGJH, mean age 10.2 (SD 0.5) years).
      Inclusion criteria for GJH were a Beighton score of >=5, with at least one
      hypermobile knee joint; for NGJH a Beighton score of <=4, and no hypermobile
      knees and for both groups no knee pain during the previous week. All children
      were recorded by five video cameras, while they walked across three force
      platforms. Net joint moments were calculated in 3D by inverse dynamics and peak
      values provided input to statistical analyses. RESULTS: In the frontal plane,
      children with GJH had a significantly lower peak knee abductor moment and peak
      hip abductor moment. In the sagittal plane, the peak knee flexor moment and the
      peak hip extensor moment were significantly lower in the GJH group although the
      absolute difference was small. CONCLUSIONS: The walking pattern was the same for
      children with GJH and for healthy children, as there were no differences in
      kinematics, but it was, however, performed with different kinetics. Children with
      GJH walked with lower ankle, knee and hip joint moments compared to children with
      NGJH. However, the clinical importance of these differences during normal gait is
      unknown. To obtain this knowledge, children with GJH must be followed
      longitudinally. TRIAL REGISTRATION: The study was approved by the Committee on
      Biomedical Research Ethics for Copenhagen and Frederiksberg, Denmark (jnr. KF01
      2006-178).

PMID- 24308707
TI  - Antimicrobial efficacy of photodynamic therapy and sodium hypochlorite on
      monoculture biofilms of Enterococcus faecalis at different stages of development.
AB  - BACKGROUND AND OBJECTIVE: As the Enterococcus faecalis biofilm ages, it is likely
      that bacteria in mature and old biofilms will become more resistant to commonly
      used antibacterial irrigants. Photodynamic therapy (PDT) has been used to kill
      resistant bacteria organized in a biofilm. This study aimed to investigate the
      antimicrobial effectiveness of 1% sodium hypochlorite (NaOCl), 2.5% NaOCl, and
      PDT on E. faecalis biofilm at different stages of development. METHODS: In this
      study 4-, 6-, and 8-week-old E. faecalis biofilms were subjected to one of the
      following approaches: phosphate-buffered saline solution (PBS), PDT, or 1% and
      2.5% NaOCl. Dentin chip suspensions were used for colony forming units (CFU)
      counting to estimate remaining E. faecalis counts. RESULTS: PDT and 2.5% NaOCl
      completely eliminated E. faecalis biofilms in three stages of biofilm
      development, whereas 1% NaOCl resulted in 81.88%, 85.73%, and 78.62% reductions
      of bacterial counts in 4-, 6-, and 8-week-old biofilms, respectively, which was
      significantly more than PBS. CONCLUSIONS: The bacteria in mature and old biofilms
      were more resistant to 1% NaOCl than were the bacteria in young biofilms. Overall
      survival and residual bacteria increase with biofilm aging. PDT and the 2.5%
      NaOCl solution were equally efficient in completely eliminating E. faecalis
      biofilms at all three stages.

PMID- 24308708
TI  - Mechanism and enantioselectivity of dirhodium-catalyzed intramolecular C-H
      amination of sulfamate.
AB  - The mechanisms and enantioselectivities of the dirhodium (Rh2L4, L = formate, N
      methylformamide, S-nap)-catalyzed intramolecular C-H aminations of 3
      phenylpropylsulfamate ester have been investigated in detail with BPW91 density
      functional theory computations. The reactions catalyzed by the Rh2(II,II)
      catalysts start from the oxidation of the Rh2(II,II) dimer to a triplet mixed
      valent Rh2(II,III)-nitrene radical, which should facilitate radical H-atom
      abstraction. However, in the Rh2(formate)4-promoted reaction, as a result of a
      minimum-energy crossing point (MECP) between the singlet and triplet profiles, a
      direct C-H bond insertion is postulated. The Rh2(N-methylformamide)4 reaction
      exhibits quite different mechanistic characteristics, taking place via a two-step
      process involving (i) intramolecular H-abstraction on the triplet profile to
      generate a diradical intermediate and (ii) C-N formation by intersystem crossing
      from the triplet state to the open-shell singlet state. The stepwise mechanism
      was found to hold also in the reaction of 3-phenylpropylsulfamate ester catalyzed
      by Rh2(S-nap)4. Furthermore, the diradical intermediate also constitutes the
      starting point for competition steps involving enantioselectivity, which is
      determined by the C-N formation open-shell singlet transition state. This
      mechanistic proposal is supported by the calculated enantiomeric excess (94.2%
      ee) with the absolute stereochemistry of the product as R, in good agreement with
      the experimental results (92.0% ee). 

PMID- 24308710
TI  - The spread and acquisition of NDM-1: a multifactorial problem.
AB  - bla NDM is a major mechanism of resistance of Gram-negative bacteria to beta
      lactam antibiotics including the carbapenems. bla NDM has been acquired by a
      large range of Gram-negative bacilli, especially by the Enterobacteriaceae and
      Acinetobacter spp. The combination of human factors (suboptimal antibiotic
      stewardship and infection control, movement of people between countries) plus
      bacterial factors (hospital adapted clones, environmental persistence and
      prolific horizontal gene transfer) have led to global spread of bla NDM at a
      rapid pace. Treatment options for New Delhi metallo-beta-lactamase (NDM)
      producers are very limited. For serious infections, combination therapy including
      a polymyxin is preferred. However, resistance to polymyxins is emerging. Clearly,
      substantial international efforts must be made to control the spread of NDM
      producers or else many of the advances of modern medicine may be undermined by
      untreatable infections. 

PMID- 24308709
TI  - Detection and clinical relevance of Staphylococcus aureus nasal carriage: an
      update.
AB  - Staphylococcus aureus nasal carriage is a well-defined risk factor of infection
      with this bacterium. The increased risk of S. aureus infection in nasal carriers
      is supported by the fact that the strains isolated from both colonization and
      infection sites are indistinguishable in most of the cases. Persistent nasal
      carriage seems to be associated with an increased risk of infection and this
      status could be defined now in clinical routine by using one or two quantitative
      nasal samples. There is evidence for supporting the detection of nasal carriage
      of S. aureus in patients undergoing cardiac surgery and in those undergoing
      hemodialysis in order to implement decolonization measures. More studies are
      needed to determine which carriers have the highest risk of infection and why
      decolonization strategies failed to reduce S. aureus infection in some other
      groups of patients. 

PMID- 24308711
TI  - Antibiotic-lock therapy: a clinical viewpoint.
AB  - Antibiotic lock therapy (ALT) - instillation of high concentrations of anti
      microbial agent with or without anti-coagulant into the lumen of central venous
      catheters - is considered a valid conservative treatment for catheter-related
      bloodstream infection (CRBSI) in patients highly dependent on maintaining the
      catheter. Results from randomized controlled studies have indicated that the
      effectiveness of ALT is moderate, but recent findings from experimental studies
      and observational case series point to considerable efficacy and safety of this
      therapy, which is usually associated with concomitant systemic treatment. In this
      article, the current knowledge about ALT for patients with CRBSI is reviewed and
      discussed, with emphasis on existing controversies and the results obtained
      according to the various uses of the catheters and the etiologies of infection. 

PMID- 24308712
TI  - Rilpivirine: drug profile of a second-generation non-nucleoside reverse
      transcriptase HIV-inhibitor.
AB  - Rilpivirine (RPV) is a next-generation non-nucleoside reverse transcriptase
      inhibitor (NNRTI) of the diarylpyrimidine family. RPV can be given once daily, is
      well absorbed and should be administered with food. It is eliminated mainly by
      hepatic metabolism. Two phase III noninferiority trials (ECHO and THRIVE),
      compared RPV 25mg with efavirenz (EFV) 600 mg, both given once daily, and
      combined with 2NRTI backbone. At week 48, response rate for pooled data were 84
      versus 82% (difference: 2%; 95% CI: -2.0 to 6.0%). EFV arms performed better than
      RPV arms when at higher baseline HIV RNA, so RPV was approved for treatment-naive
      patients with HIV RNA below 100,000 copies/ml. Approximately 90% of viruses
      phenotypically resistant to RPV showed cross-resistance to ETR. Conversely,
      phenotypic analysis showed that in EFV arm, none were resistant to the second
      generation NNRTIs. CD4 count increases were similar between groups, but RPV
      showed a lower rate of discontinuation due to adverse events and lower rates of
      central nervous system effects, rash and lipid abnormalities. Potency,
      tolerability and co-formulation in a single tablet (Eviplera((r)), Complera((r)))
      make this drug a new and attractive option for the treatment of HIV. 

PMID- 24308713
TI  - New strategies against Stenotrophomonas maltophilia: a serious worldwide
      intrinsically drug-resistant opportunistic pathogen.
AB  - Stenotrophomonas maltophilia is a worldwide human opportunistic pathogen
      associated with serious infections in humans, and is most often recovered from
      respiratory tract infections. In addition to its intrinsic drug resistance, this
      organism may acquire resistance via multiple molecular mechanisms. New
      antimicrobial strategies are needed to combat S. maltophilia infections,
      particularly in immunocompromised patients, cystic fibrosis patients with
      polymicrobial infections of the lung, and in patients with chronic infections.
      This editorial reports on newer drugs and antimicrobial strategies and their
      potential for use in treatment of S. maltophilia infections, the development of
      new technologies to detect this organism, and identifies strategies currently in
      use to reduce transmission of this pathogen. 

PMID- 24308714
TI  - Emergence of carbapenemases in Pseudomonas aeruginosa: a worldwide problem.
AB  - The emergence of carbapenemases-producing Pseudomonas aeruginosa isolates,
      resistant to all antibiotics except colistin, is an important health problem due
      to the lack of effective antibiotic treatments. This article assesses the
      findings of a recently published investigation performed in Belarus, Kazakhstan
      and Russia, where a longitudinal epidemiological and clinical study of
      extensively drug-resistant P. aeruginosa was performed. This study highlights the
      progressive increase of VIM-2-positive ST235 P. aeruginosa via clonal
      dissemination. Strategies to prevent this emergency problem and a global
      surveillance system are needed in order to minimize this worldwide problem.

PMID- 24308715
TI  - State of the art syphilis diagnostics: rapid point-of-care tests.
AB  - Syphilis remains an important and entirely preventable cause of stillbirth and
      neonatal mortality. More than 1 million women with active syphilis become
      pregnant each year. Without treatment, 25% of them will deliver a stillborn baby,
      33% will deliver a live low-birth weight baby with an increased chance of dying
      in the first month of life. Adverse pregnancy outcomes due to syphilis can be
      prevented by screening pregnant women, and treating those who test positive with
      a single dose of penicillin before 28 weeks gestation. Until recently access to
      screening in low- and middle-income countries has been limited, since screening
      tests have been laboratory based, requiring equipment, electricity and trained
      laboratory staff. Now a number of rapid, cheap, simple and accurate screening
      tests are available and can give a result in 15-20 min, enabling those who
      require treatment to be treated at their first visit. 

PMID- 24308716
TI  - Statistical modelling of networked human-automation performance using working
      memory capacity.
AB  - This study examines the challenging problem of modelling the interaction between
      individual attentional limitations and decision-making performance in networked
      human-automation system tasks. Analysis of real experimental data from a task
      involving networked supervision of multiple unmanned aerial vehicles by human
      participants shows that both task load and network message quality affect
      performance, but that these effects are modulated by individual differences in
      working memory (WM) capacity. These insights were used to assess three
      statistical approaches for modelling and making predictions with real
      experimental networked supervisory performance data: classical linear regression,
      non-parametric Gaussian processes and probabilistic Bayesian networks. It is
      shown that each of these approaches can help designers of networked human
      automated systems cope with various uncertainties in order to accommodate future
      users by linking expected operating conditions and performance from real
      experimental data to observable cognitive traits like WM capacity. Practitioner
      Summary: Working memory (WM) capacity helps account for inter-individual
      variability in operator performance in networked unmanned aerial vehicle
      supervisory tasks. This is useful for reliable performance prediction near
      experimental conditions via linear models; robust statistical prediction beyond
      experimental conditions via Gaussian process models and probabilistic inference
      about unknown task conditions/WM capacities via Bayesian network models. 

PMID- 24308717
TI  - N- and O-glycosylation analysis of etanercept using liquid chromatography and
      quadrupole time-of-flight mass spectrometry equipped with electron-transfer
      dissociation functionality.
AB  - Etanercept is a highly glycosylated therapeutic Fc-fusion protein that contains
      multiple N- and O-glycosylation sites. An in-depth characterization of the
      glycosylation of etanercept was carried out using liquid chromatography/mass
      spectrometry (LC/MS) methods in a systematic approach in which we analyzed the N-
      and O-linked glycans and located the occupied O-glycosylation sites. Etanercept
      was first treated with peptide N-glycosidase F to release the N-glycans. The N
      glycan pool was labeled with a 2-aminobenzamide (2-AB) fluorescence tag and
      separated using ultraperformance liquid chromatography-hydrophilic interaction
      liquid chromatography (UPLC-HILIC). Preliminary structures were assigned using
      Glycobase. These assignments, which included monosaccharide sequence and linkage
      information, were confirmed by exoglycosidase array digestions of aliquots of the
      N-glycan pool. The removal of the N-glycans from etanercept facilitated the
      selective characterization of O-glycopeptides and enabled the O-glycans to be
      identified. These were predominantly of the core 1 subtype (HexHexNAc O
      structure) attached to Ser/Thr residues. alpha2->3,6,8,9 sialidase was used to
      remove the sialic acid residues on the O-glycans allowing the use of an automated
      LC/MS(E) protocol to identify the O-glycopeptides. Electron-transfer dissociation
      (ETD) was then used to pinpoint the 12 occupied O-glycosylation sites. The
      determination of N- and O-glycans and O-glycosylation sites in etanercept
      provides a basis for future studies addressing the biological importance of
      specific protein glycosylations in the production of safe and efficacious
      biotherapeutics. 

PMID- 24308719
TI  - Three-component reaction between alkynes, elemental sulfur, and aliphatic amines:
      a general, straightforward, and atom economical approach to thioamides.
AB  - A general, straightforward, and atom-economical three-component synthesis of
      thioamides from alkynes, elemental sulfur, and aliphatic amines has been
      developed. 

PMID- 24308718
TI  - Foot-and-mouth disease: past, present and future.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
      animals including cattle, pigs, sheep and many wildlife species. It can cause
      enormous economic losses when incursions occur into countries which are normally
      disease free. In addition, it has long-term effects within countries where the
      disease is endemic due to reduced animal productivity and the restrictions on
      international trade in animal products. The disease is caused by infection with
      foot-and-mouth disease virus (FMDV), a picornavirus. Seven different serotypes
      (and numerous variants) of FMDV have been identified. Some serotypes have a
      restricted geographical distribution, e.g. Asia-1, whereas others, notably
      serotype O, occur in many different regions. There is no cross-protection between
      serotypes and sometimes protection conferred by vaccines even of the same
      serotype can be limited. Thus it is important to characterize the viruses that
      are circulating if vaccination is being used for disease control. This review
      describes current methods for the detection and characterization of FMDVs.
      Sequence information is increasingly being used for identifying the source of
      outbreaks. In addition such information can be used to understand antigenic
      change within virus strains. The challenges and opportunities for improving the
      control of the disease within endemic settings, with a focus on Eurasia, are
      discussed, including the role of the FAO/EuFMD/OIE Progressive Control Pathway.
      Better control of the disease in endemic areas reduces the risk of incursions
      into disease-free regions. 

PMID- 24308720
TI  - The association of UGT1A1*6 and UGT1A1*28 with irinotecan-induced neutropenia in
      Asians: a meta-analysis.
AB  - BACKGROUND: The UGT1A1*28 polymorphism is known as a biomarker of irinotecan
      induced neutropenia in Caucasians. However, in Asians, the UGT1A1*28 mutation is
      much less frequent. METHODS: A meta-analysis was performed to assess the
      association of the UGT1A1*6 and UGT1A1*28 with neutropenia in Asians. RESULTS: In
      a combination test of the two variations, patients with severe neutropenia
      displayed a 155% higher mutational load than those that were not neutropenic (ORG
      = 2.55; 95% CI: 1.82-3.58). CONCLUSIONS: In Asians, a combination test of
      UGT1A1*6 and UGT1A1*28 might be a potential biomarker of irinotecan-induced
      neutropenia, an observation that will need additional trials for confirmation.

PMID- 24308721
TI  - Effect of semen and seminal amyloid on vaginal transmission of simian
      immunodeficiency virus.
AB  - BACKGROUND: Semen and semen-derived amyloid fibrils boost HIV infection in vitro
      but their impact on sexual virus transmission in vivo is unknown. Here, we
      examined the effect of seminal plasma (SP) and semen-derived enhancer of virus
      infection (SEVI) on vaginal virus transmission in the SIV/rhesus macaque (Macacca
      mulatta) model. RESULTS: A total of 18 non-synchronized female rhesus macaques
      (six per group) were exposed intra-vaginally to increasing doses of the
      pathogenic SIVmac239 molecular clone in the presence or absence of SEVI and SP.
      Establishment of productive virus infection was assessed by measuring plasma
      viral RNA loads at weekly intervals. We found that the first infections occurred
      at lower viral doses in the presence of SP and SEVI compared to the control
      group. Furthermore, the average peak viral loads during acute infection were
      about 6-fold higher after exposure to SP- and SEVI-treated virus. Overall
      infection rates after a total of 27 intra-vaginal exposures to increasing doses
      of SIV, however, were similar in the absence (4 of 6 animals) and presence of SP
      (5 of 6), or SEVI (4 of 6). Furthermore, the infectious viral doses required for
      infection varied considerably and did not differ significantly between these
      three groups. CONCLUSIONS: Semen and SEVI did not have drastic effects on vaginal
      SIV transmission in the present experimental setting but may facilitate spreading
      of virus infection after exposure to low viral doses that most closely
      approximate the in vivo situation.

PMID- 24308722
TI  - Metrological challenges for reconstruction of 3-D microstructures by focused ion
      beam tomography methods.
AB  - The development of combined focused ion beam and scanning electron microscopes
      has enabled significant advances in the characterization of the 3-D structure of
      materials. The repeated removal of thin layers or slices with an ion beam and
      imaging or mapping the chemical or crystallographic structure of each slice
      enables a 3-D reconstruction from the images or maps. The accuracy of the
      reconstruction thus depends on the accuracy with which the slice thickness is
      measured and maintained throughout the process, and the alignment accuracy of the
      slices achieved during acquisition or by postacquisition corrections. A survey of
      papers published in this field suggests that the reconstruction accuracy is not
      often considered or reported. Using examples from examination of the 3-D
      structure of hardmetals, issues affecting the accuracy of slice thicknesses and
      image realignments are examined and illustrated and potential errors quantified
      by the use of fiducial markers and the expected isotropy of the hardmetal
      structure itself. 

PMID- 24308723
TI  - Testosterone replacement therapy improves metabolic parameters in hypogonadal men
      with type 2 diabetes but not in men with coexisting depression: the BLAST study.
AB  - INTRODUCTION: The association between testosterone deficiency and insulin
      resistance in men with type 2 diabetes is well established and current endocrine
      society guidelines recommend the measurement of testosterone levels in all men
      with type 2 diabetes or erectile dysfunction. AIM: We report the first double
      blind, placebo-controlled study conducted exclusively in a male type 2 diabetes
      population to assess metabolic changes with long-acting testosterone undecanoate
      (TU). METHODS: The type 2 diabetes registers of seven general practices
      identified 211 patients for a 30-week double-blind, placebo-controlled study of
      long-acting TU 1,000 mg followed by 52 weeks of open-label use. Because of the
      established impact of age, obesity, and depression on sexual function, these
      variables were also assessed for influence on metabolic parameters. MAIN OUTCOME
      MEASURE: Changes in glycated hemoglobin (HbA1c) and the level of testosterone at
      which response are achieved. RESULTS: Treatment with TU produced a statistically
      significant reduction in HbA1c at 6 and 18 weeks and after a further 52 weeks of
      open-label medication most marked in poorly controlled patients with baseline
      HbA1c greater than 7.5 where the reduction was 0.41% within 6 weeks, and a
      further 0.46% after 52 weeks of open-label use. There was significant reduction
      in waist circumference, weight, and body mass index in men without depression,
      and improvements were related to achieving adequate serum levels of testosterone.
      There were no significant safety issues. CONCLUSIONS: Testosterone replacement
      therapy significantly improved HbA1c, total cholesterol, and waist circumference
      in men with type 2 diabetes. Improvements were less marked in men with depression
      at baseline, and therapeutic responses were related to achieving adequate serum
      testosterone levels. Current advice on 3- to 6-month trials of therapy may be
      insufficient to achieve maximal response. Patients reported significant
      improvements in general health.

PMID- 24308724
TI  - Von Willebrand Factor as a new marker for non-invasive assessment of liver
      fibrosis and cirrhosis in patients with chronic hepatitis C.
AB  - BACKGROUND: Staging of liver fibrosis in patients with chronic hepatitis C (CHC)
      is recommended prior to anti-viral therapy. As vWF-Ag was shown as a predictor of
      portal hypertension, decompensation and mortality in patients with liver
      cirrhosis, we performed this study to investigate if vWF-Ag is able to predict
      different fibrosis stages and if it is comparable to other fibrosis scores. AIM:
      To investigate if vWF-Ag is able to predict different fibrosis stages and if it
      is comparable to other fibrosis scores. METHODS: We analysed 294 patients with
      chronic hepatitis C who underwent biopsy. We assessed stage of liver fibrosis
      according to Metavir, measured vWF-Ag and calculated different fibrosis scores
      (APRI, FCI, FORNS, FI, Fib-4) and compared them by AUCs. We also calculated a new
      score: vWF-Ag/thrombocytes (VITRO score) for prediction of fibrosis. RESULTS: vWF
      Ag levels were increasing with stage of fibrosis: F0: vWF-Ag was median 136.5%,
      FI 140.6%, FII 157.5%, FIII 171.0%, FIV 252.0%; P < 0.001. vWF-Ag and VITRO score
      produced AUCs of 0.7 and 0.72 for >=F2, comparable to the AUCs of APRI, Fib-4,
      FORNS with 0.75, 0.65 and 0.64 (P > 0.05). For >=F3 AUCs were 0.79 and 0.86 for
      vWF-Ag and VITRO score, comparable with AUCs of 0.79, 0.86 and 0.87 for APRI, Fib
      4 and FORNS. Cirrhosis shows AUCs of 0.84 and 0.89 for vWF-Ag and VITRO score,
      APRI, Fib-4 and FORNS showed similar results with AUCs of 0.82, 0.88 and 0.87.
      CONCLUSIONS: vWF-Ag and VITRO score offer an easy possibility to evaluate the
      stage of fibrosis to diagnose subclinical cirrhosis in patients with chronic
      hepatitis C. Both vWF-Ag and VITRO score show equal performance in comparison to
      other fibrosis scores assessed in our study.

PMID- 24308726
TI  - Current treatment status of polycystic liver disease in Japan.
AB  - AIM: Polycystic liver disease (PLD) is a genetic disorder characterized by the
      progressive development of multiple liver cysts. No standardized criteria for the
      selection of treatment exist because PLD is a rare condition and most patients
      are asymptomatic. We here aimed to clarify the status of treatment and to present
      a therapeutic strategy for PLD in Japan. METHODS: From 1 June 2011 to 20 December
      2011, we administered a questionnaire to 202 PLD patients from 86 medical
      institutions nationwide. RESULTS: The patients included 45 men and 155 women, and
      the median age was 63 years. Two hundred and eighty-one treatments were performed
      for these patients, as follows: cyst aspiration sclerotherapy (AS) in 152 cases,
      cyst fenestration (FN) in 53, liver resection (LR) in 44, liver transplantation
      (LT) in 13 and other treatments in 19. For cases of type I PLD (mild form)
      according to Gigot's classification, the therapeutic effects of AS, FN and LR
      were similar. For type II (moderate form), LT demonstrated the best therapeutic
      effects, followed by LR and FN. For type III (severe form), the effects of LT
      were the best. The incidences of complications were 23.0% in AS, 28.4% in FN,
      31.8% in LR and 61.5% in LT. CONCLUSION: Considering the therapeutic effects and
      complications, AS, LR and LT showed good results for type I, type II and type III
      PLD, respectively. However, LT for PLD was performed in a small number of
      patients. In Japan, the transplantation therapy is expected to be common in the
      future.

PMID- 24308725
TI  - STAT inhibitors for cancer therapy.
AB  - Signal Transducer and Activator of Transcription (STAT) proteins are a family of
      cytoplasmic transcription factors consisting of 7 members, STAT1 to STAT6,
      including STAT5a and STAT5b. STAT proteins are thought to be ideal targets for
      anti-cancer therapy since cancer cells are more dependent on the STAT activity
      than their normal counterparts. Inhibitors targeting STAT3 and STAT5 have been
      developed. These included peptidomimetics, small molecule inhibitors and
      oligonucleotides. This review summarized advances in preclinical and clinical
      development of these compounds. 

PMID- 24308727
TI  - Components of pain assessment after laparoscopic donor nephrectomy.
AB  - BACKGROUND: Pain after laparoscopic surgery can be divided into three components:
      incisional or superficial wound pain, deep intra-abdominal pain and referred
      shoulder pain. Better understanding and adequate assessment of post-operative
      pain may be an important clue to the optimisation of recovery after laparoscopic
      surgery. Therefore, we performed a components of pain assessment after
      laparoscopic donor nephrectomy. METHODS: Twenty patients who underwent a
      laparoscopic donor nephrectomy were included in this prospective study. Pain was
      subdivided into three components: superficial wound pain, deep intra-abdominal
      pain and referred shoulder pain, and for each component a numeric rating scale
      (from 0 to 10) was obtained at 1, 24 and 48 h after surgery. RESULTS: Repeated
      measurements analysis of variance showed that during the first 48 h after
      surgery, the superficial wound and deep intra-abdominal pain components were
      significantly higher as compared with the referred shoulder pain component.
      Although the deep intra-abdominal pain component was slightly higher as compared
      with superficial wound pain, this difference was not significant (P = 0.097).
      Further assessment of superficial wound pain showed that the Pfannenstiel
      incision was the most significant determinant of this component of pain (P =
      0.004), whereas deep intra-abdominal pain was significantly higher at the
      ipsilateral side of the abdomen (P = 0.015). DISCUSSION: The components of pain
      assessment revealed that pain related to the Pfannenstiel incision and the deep
      intra-abdominal pain component are the most important determinants of pain after
      laparoscopic donor nephrectomy. Further improvement of the management of post
      operative pain should focus on these components of pain.

PMID- 24308728
TI  - Effectiveness of spirometry as a motivational tool for smoking cessation: a
      clinical trial, the ESPIMOAT study.
AB  - BACKGROUND: Smoking is the main preventable cause of morbidity and mortality in
      our region, it being the main causative agent of chronic obstructive pulmonary
      disease. There still is no consensus on the use of spirometry as a strategy for
      smoking cessation, given that there is insufficient scientific evidence from high
      quality studies to recommend the use of this technique. METHODS/DESIGN: This is
      to be a randomized, multicentre, open-label clinical trial. A total of 444
      smokers over 40 years of age will be recruited by 39 general practitioners from
      22 health centers. Primary objective of this study is to assess the effectiveness
      of spirometry together with information regarding the test for smoking cessation
      after 1 year in smokers over 40 years of age with a more than 10 pack-year
      history and no previous diagnosis of chronic obstructive pulmonary disease.
      Groups of 45 patients who smoke will be randomly selected from the lists of the
      participating doctors. The names will be sent to the corresponding doctors who
      will contact candidate patients and assess whether they meet the selection
      criteria. Patients who meet these criteria will be randomly allocated to an
      intervention or control group. For patients in both groups, a nurse will conduct
      an interview and perform a spirometry test to measure forced vital capacity.
      Then, all patients will be referred for an appointment with their doctor for
      brief anti-smoking intervention, patients from the intervention group
      additionally being informed about the result of the spirometry test. After 1
      year, smoking status will be assessed and, in those who report that they have
      quit smoking, abstinence will be confirmed by co-oximetry. Data will be analyzed
      on an intention-to-treat basis using the chi-squared test for outcomes and binary
      logistic regression if it is considered to be necessary to adjust for confounding
      variables. DISCUSSION: Performing a spirometry test and providing information on
      pulmonary function may increase awareness of the effect of smoking among smokers
      who are asymptomatic or have few symptoms and make them decide to quit.
      Specifically, in patients with chronic obstructive pulmonary disease it might
      increase levels of motivation to quit smoking in early stages of the disease. If
      this strategy were to be effective, it could be included in the health promotion
      activities offered in primary care. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01821885.

PMID- 24308729
TI  - Status of pediatric anesthesiology fellowship research education in the United
      States: a survey of fellowship program directors.
AB  - BACKGROUND: Currently, very little information is known regarding the research
      education of pediatric anesthesia fellows. OBJECTIVE: The main objective of the
      current investigation was to evaluate the status of research training in
      pediatric anesthesia fellowship programs in the United States. METHODS: Survey
      responses were solicited from forty-six pediatric anesthesia fellowship
      directors. Questions evaluated department demographic information, the extent of
      faculty research activity, research resources and research funding in the
      department, the characteristics of fellow research education and fellow research
      productivity, departmental support for fellow research, and perceived barriers to
      fellow research education. RESULTS: Thirty-six of forty-six fellowship directors
      responded to the survey, for a response rate of 78%. Eight of fourteen (57%)
      programs with a structured curriculum had more than 20% of graduating fellows
      publish a peer-reviewed manuscript compared with only five of twenty-two (23%)
      programs, which did not have a structured research curriculum (P = 0.03). While
      the majority of program directors (thirty of thirty-six (83%)) did not think that
      fellows are adequately trained to pursue research activities, only a minority of
      program directors (7 of 36 (19%)) thought that an extra year of fellowship
      dedicated to research should become a requirement. CONCLUSION: Structured
      research curriculum is associated with increased research productivity during
      pediatric anesthesia fellowship. Important barriers to fellows' research
      education include high clinical demands and lack of research time for faculty.
      Despite acknowledging the poor research education, a small minority of fellowship
      directors supports the addition of an extra year exclusively dedicated to
      research.

PMID- 24308730
TI  - Risk factors for early fatal outcomes among children with hemophagocytic
      lymphohistiocytosis (HLH): a single-institution case-series in Vietnam.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal hematological
      syndrome that causes a disturbance of the immune system. Overall mortality of HLH
      is greater than 50% and the majority of patients who die do so within the first 8
      weeks of chemotherapy treatment. To find clinical parameters relating to high
      risk HLH patients, this study examined associations between an early fatal
      outcome and potential prognostic clinical factors and laboratory findings on
      admission. Eighty-nine pediatric HLH patients were prospectively recruited in
      Children's Hospital No. 1, Ho-Chi-Minh City, Vietnam, during the period from
      January 2010 to August 2012. Associations between early fatal outcome and
      clinical and laboratory findings, including a cerebrospinal fluid examination and
      virological test on admission, were examined. During the 8-week therapy, 25 (28%)
      HLH patients died. Persistent fever (>2 weeks), severe thrombocytopenia (<75 *
      10(9)/L), hyperbilirubinemia, and prolonged activated partial thromboplastin time
      (APTT) (>33 sec) were significant risk factors of early fatal outcome.
      Multivariate logistic regression analysis revealed that thrombocytopenia and
      prolonged APTT (P for trend was 0.054 and 0.013, respectively) were independently
      associated with the early fatal outcome. Persistent fever, severe
      thrombocytopenia, hyperbilirubinemia, and prolonged APTT on admission will be
      useful and practical predictors to determine high-risk HLH patients. 

PMID- 24308731
TI  - The unbearable lightness of MCI.

PMID- 24308732
TI  - Comment on "solid recovered fuel: materials flow analysis and fuel property
      development during the mechanical processing of biodried waste".

PMID- 24308733
TI  - Second LifeTM: a novel simulation platform for the training of surgical
      residents.
AB  - A virtual world is a three-dimensional, computer-generated, simulated
      environment. Human users create "avatars," or virtual projections of themselves,
      in order to explore this virtual environment and interact with the objects and
      structures inside it. Second LifeTM is one such virtual world accessible freely
      via the internet, which has been used to construct a virtual hospital complete
      with reception areas, changing rooms, offices, and hospital wards. Early
      pioneering studies have demonstrated the advantages of using virtual worlds in
      the education of surgical residents in a number of ways, from introductions to
      the clinical environment, initial patient assessment, and managing adverse
      outcomes, to gaining informed consent, hospital-wide training, and medical device
      development. 

PMID- 24308735
TI  - Radio-guided localization of clinically occult breast lesions: current modalities
      and future directions.
AB  - The extensive availability of breast cancer screening programs and improvement in
      diagnostic imaging have led to more frequent detection of suspicious and
      clinically occult breast lesions. Early detection of tumor is important for
      breast-conserving treatment. Incomplete excision is a major risk factor for local
      recurrence. Following precise localization and removing the entire lesion while
      achieving adequate clear margins is the key factor for successful management of
      non-palpable breast lesions. For this purpose, several techniques such as wire
      guided localization, intra-operative ultrasound guided resection, radio-guided
      occult lesion localization and radioactive seed localization have been described
      and applied. In this article, we overview the two commonly used localization
      techniques, radio-guided occult lesion localization and wire-guided localization,
      particularly describing their advantages and drawbacks. 

PMID- 24308734
TI  - The functional performance of the Argus II retinal prosthesis.
AB  - Visual prostheses are devices to treat profound vision loss by stimulating nerve
      cells anywhere along the visual pathway, typically with electrical pulses. The
      Argus II implant, developed by Second Sight Medical Products (SSMP, Sylmar, CA,
      USA), targets the retina and features 60 electrodes that electrically stimulate
      the surviving retinal neurons. Of the approximately 20 research groups that are
      actively developing visual prostheses, SSMP has the longest track record. The
      Argus II was the first visual prosthesis to become commercially available: it
      received the European conformity mark in 2011 and FDA approval was granted in
      early 2013 for humanitarian use in the USA. Meanwhile, the Argus II
      safety/benefit study has been extended for research purposes, and is still
      ongoing. In this review, we will discuss the performance of the Argus II in
      restoring sight to the blind, and we will shed light on its expected developments
      in the coming years.

PMID- 24308736
TI  - Biologic matrices in oncologic breast reconstruction after mastectomy.
AB  - As the demand for post-mastectomy breast reconstruction has continued to rise,
      options for the implantable soft-tissue replacement products which enhance the
      aesthetic and reconstructive outcome of these procedures has grown as well. While
      the most common product used in an alloplastic breast reconstruction is an
      acellular dermal matrix derived from human sources, many other options are
      currently available, each offering their own unique properties and benefits. This
      review presents a concise description of each of the biologic matrices currently
      available and discusses their use in the context of one-stage and two-stage
      breast reconstructions. 

PMID- 24308737
TI  - Transcatheter tissue engineered heart valves.
AB  - Valvular heart disease represents a leading cause of mortality worldwide.
      Transcatheter heart valve replacement techniques have been recently introduced
      into the clinical routine expanding the treatment options for affected patients.
      However, despite this technical progress toward minimally invasive, transcatheter
      strategies, the available heart valve prostheses for these techniques are
      bioprosthetic and associated with progressive degeneration. To overcome such
      limitations, the concept of heart valve tissue engineering has been repeatedly
      suggested for future therapy concepts. Ideally, a clinically relevant heart valve
      tissue engineering concept would combine minimally invasive strategies for both,
      living autologous valve generation as well as valve implantation. Therefore,
      merging transcatheter techniques with living tissue engineered heart valves into
      a trascatheter tissue engineered heart valve concept could significantly improve
      current treatment options for patients suffering from valvular heart disease.
      This report provides an overview on transcatheter tissue engineered heart valves
      and summarizes available pre-clinical data. 

PMID- 24308738
TI  - The use of cryoablation in treating liver tumors.
AB  - Percutaneous image-guided tumor ablation techniques have been used as an
      alternative method for patients with unresectable liver tumors. Although all
      techniques avoid morbidity and mortality of major surgery and have advantage of
      preserving non-tumoral liver parenchyma, cryoablation currently is the only
      percutaneous ablation technique allowing intraprocedural monitoring because of
      visibility of its ablation effect with computed tomography and MRI. Cryoablation
      uses extremely low temperatures to induce local tissue necrosis to treat both
      primary and metastatic liver tumors. This article discusses the principles of
      liver tumor percutaneous cryoablation, including mechanisms of tissue injury,
      technique, equipment, image-guidance used, patient selection criteria, clinical
      outcome and complications as well as current trends and future goals. 

PMID- 24308739
TI  - Challenges facing in vivo tracking of mesenchymal stem cells used for tissue
      regeneration.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) are increasingly being
      investigated in the field of regenerative medicine. In vivo monitoring of MSCs
      can be performed with MRI, which is a non-invasive, non-toxic and clinically
      acceptable modality. In order to track these MSCs, cells must be labeled with
      detectable magnetic nanoparticles. However, they 'leak' from labeled cells,
      limiting their surveillance to a 3-week period. Li et al. developed a rodent
      model in order to evaluate MRI monitoring of intramuscularly injected
      aminopropyltriethoxysilane iron oxide-labeled MSCs. Both in vivo tracking and
      histological analysis were undertaken. Seeded MSCs demonstrated increased MRI
      signal in the labeled test group over 3 weeks compared with the unlabeled
      controls. Histological Prussian blue staining of posttermination tissues
      confirmed these findings. The authors conclude that successful labeling of MSCs
      is possible with aminopropyltriethoxysilane - magnetic nanoparticles and that
      these cells can be monitored in vivo. They offer this form of labeling as an
      alternative to more common dextran-coated magnetic nanoparticles.

PMID- 24308740
TI  - A robot for transnasal surgery featuring needle-sized tentacle-like arms.
AB  - This paper discusses a new class of robots known as concentric tube robots and
      their application to transnasal skull base surgery. The endonasal approach has
      clear benefits for patients, but the surgery presents challenges that strongly
      motivate the use of robotic tools. In this paper, the concentric tube robot
      concept is described, and preliminary experimental results for transnasal skull
      base surgery are reviewed. Just as the da Vinci robot has revolutionized many
      laparoscopic surgeries, we expect concentric tube robots will enable the
      advancement of skull base surgery and the development of other minimally invasive
      procedures that require access through constrained paths. 

PMID- 24308741
TI  - Improving ablation strategies for the treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in
      clinical practice. The contemporary management of AF is centered on symptomatic
      improvement, as well as reduction in the AF associated morbidity and mortality.
      For many highly symptomatic patients catheter ablation offers an efficacious
      means to maintaining sinus rhythm when antiarrhythmic drugs have been
      ineffective, are contraindicated or cannot be tolerated. Over the past 15 years,
      catheter ablation has moved from an 'experimental therapy' to the standard of
      care for the maintenance of sinus rhythm. Unfortunately, while the results of
      ablation are unequivocally superior to medical therapy, recognized limitations of
      the contemporary AF ablation procedures have spurred several developments
      designed to improve the efficacy of the index ablation procedure, while limiting
      adverse events. The purpose of this review is to discuss the procedural
      refinements, and technological innovations proposed to outcomes of patients
      undergoing a percutaneous catheter ablation procedure for AF. 

PMID- 24308742
TI  - Parent preference in Switzerland for easy-to-use attributes of growth hormone
      injection devices quantified by willingness to pay.
AB  - Sustained treatment adherence, usually over long periods of time, is critical to
      the success of growth hormone (GH) therapy. However, adherence rates are often
      poor which may result in suboptimal clinical outcomes. The type of device used by
      patients to administer their GH can influence adherence. Offering patients a
      choice of device maximizes the chance of adherence to treatment. Multiple factors
      will influence a patient's choice of device, depending on individual priorities.
      This study evaluated the most preferred features of GH injection devices by
      parents using a web-based questionnaire and as assessed by their willingness to
      pay for specific device features. The results show that parents are willing to
      pay for device features facilitating ease of use. 

PMID- 24308743
TI  - Repair of the anterior mitral leaflet prolapse.
AB  - Repair of anterior mitral leaflet prolapse is one of the most challenging aspects
      in mitral valve repair surgery. In this review, we discuss the various techniques
      developed over the past three to four decades for the repair of anterior mitral
      leaflet prolapse, debate the pros and cons of each and compare their results,
      keeping reoperation for recurrent mitral regurgitation as the focal point of
      follow-up. At our center, chordal replacement with artificial expanded
      polytetrafluoroethylene sutures in the form of premeasured loops is the most
      commonly used technique for repair of anterior mitral leaflet prolapse for the
      past decade. We recommend and provide justification for the use of this
      technique, especially when mitral valve repair is performed through a minimally
      invasive approach. We believe that the trend towards a minimally invasive
      approach for mitral valve repair will exponentially increase in the next 5-10
      years, at least until percutaneous techniques, if at all, become more reliable
      and safe. 

PMID- 24308744
TI  - Of rough starts and smooth finishes: correlations between post-anesthesia care
      unit and postoperative days 1-5 pain scores.
AB  - OBJECTIVE: The goal of this project was to explore the association between post
      anesthesia care unit (PACU) pain scores recorded within the first and second hour
      of the end of surgery with maximum and median pain scores recorded on
      postoperative days (PODs) 1 through 5. DESIGN: This study was a retrospective
      cohort study of clinically documented pain scores in a mixed surgical population.
      SETTING: This study was set in a single tertiary-care teaching hospital over a 1
      year time period. PATIENTS: All patients were adult patients undergoing a single,
      non-ambulatory, non-obstetric surgical procedure. MEASURES: Pain scores, measured
      using the numerical rating scale, from PODs 0 through 5 were obtained from an
      integrated data repository. Kendall's Tau-b correlations were then calculated
      between maximum pain scores occurring within each of the two PACU time periods
      and maximum and median pain scores in each of the five ensuing PODs. RESULTS: A
      total of 349,797 pain scores from 8,332 patients were reviewed. Correlations
      between maximum pain score by time period demonstrated a significant and high
      correlation at Tau-b = 0.86, between 1-hour PACU pain scores and 2-hour PACU pain
      scores. However, the correlation of maximum pain scores recorded in the PACU with
      those recorded on PODs 1 through 5 was significantly lower, ranging from 0.19 to
      0.27. The correlation of maximum PACU pain score with median pain scores recorded
      on PODs 1 through 5 ranged from 0.22 to 0.29. The correlation structures of the
      PODs 1 through 5 median pain scores may be consistent with an autoregressive
      pattern. CONCLUSIONS: Maximum scores measured within the PACU likely reflect a
      set of circumstances distinct from those experienced on PODs 1 through 5.

PMID- 24308745
TI  - Dynamics of anti-Mullerian hormone during controlled ovarian stimulation.
AB  - AIM: To evaluate the dynamics of anti-Mullerian hormone (AMH) during controlled
      ovarian stimulation (COH) and to correlate changes in AMH to age, estradiol (E2)
      levels, and the presence of polycystic ovary syndrome (PCOS). METHODS: Data were
      retrospectively collected from women presenting for COH in the outpatient clinic
      of a university hospital between January and July 2011. Concentrations of AMH and
      E2 during COH with gonadotropins for in vitro fertilization (IVF) (n = 68) and
      clomiphene or low-dose gonadotropin stimulation cycles (n = 27) for intrauterine
      insemination were evaluated. Percentage change in AMH and E2 from pre-stimulation
      values was calculated. Dynamics of hormonal changes were analyzed using non
      parametric tests. Correlations between changes in AMH and E2 were analyzed with
      Spearman correlation. RESULTS: During IVF stimulation, AMH declined steadily from
      pre-stimulation values. No significant change in AMH dynamics was observed during
      clomiphene or low-dose stimulation cycles. Percentage decline in AMH during IVF
      stimulation correlated with rise in E2 at all time points. CONCLUSIONS: The
      observed phenomena contribute to an improved understanding of AMH expression and
      its role in the follicular development. Our data support the concept that AMH is
      produced by secondary, preantral and small antral follicles in the early part of
      stimulation and declines as these follicles are recruited into dominant growing
      follicles.

PMID- 24308746
TI  - The effectiveness of a stratified group intervention using the STarTBack
      screening tool in patients with LBP--a non randomised controlled trial.
AB  - BACKGROUND: Low back pain (LBP) is costly to society and improving patient
      outcomes is a priority. Stratifying LBP patients into more homogenous groups is
      advocated to improve patient outcome. The STarT Back tool, a prognostic screening
      tool has demonstrated efficacy and greater cost effectiveness in physiotherapy
      settings. The management of LBP patients in groups is common but to date the
      utility of the STarT Back tool in group settings has not been explored. The aim
      of this study is to determine if the implementation of 'stratified care' when
      delivered in a group setting will lead to significantly better physical and
      psychological outcomes and greater cost effectiveness in LBP patients compared to
      a bestcare historical control group. METHODS/DESIGN: This study is a non
      randomised controlled trial. Low back pain patients recruited from the Waterford
      Primary Care area (population = 47,000) will be stratified into low, medium or
      high risk of persisting symptoms using the STarT Back Tool. Low risk patients
      will be offered a single one off education/exercise class offering positive
      messages on LBP management in line with recommended guidelines. Medium risk
      patients will be offered a 12 week group exercise/education intervention
      addressing their dominant physical obstacles to recovery. A 12 week group
      cognitive behavioural approach will be delivered to the high risk patients,
      characterised by the presence of high levels of psychosocial prognostic factors.
      These patients will be compared with a historical control group where therapists
      were blinded as to the risk stratification of patients and a generic group
      intervention was delivered to all patients, irrespective of their initial risk
      stratification. The primary outcome measure will be disability (Roland Morris
      Disability Questionnaire). Secondary outcomes will include back pain intensity
      (Visual Analogue Scale), distress (Distress and Risk Assessment Method), back
      beliefs (Back Beliefs Questionnaire), health status (Euroqol), global benefit (7
      point likert scale), satisfaction (7 point likert scale), cost effectiveness and
      functional status. Outcome will be measured at baseline, 12 weeks and 6 months.
      DISCUSSION: This paper details the rationale, design, methods, planned analysis
      and operational aspects of a study examining the utility of the STarT Back Tool
      as a 'stratification tool for targeted treatment' in a group intervention. TRIAL
      REGISTRATION: Current controlled trials: ACTRN12613000431729.

PMID- 24308747
TI  - Identification of risk factors associated with disclosure of false positive
      bovine tuberculosis reactors using the gamma-interferon (IFNgamma) assay.
AB  - The gamma-interferon assay (IFNgamma) is often used as an ancillary diagnostic
      test alongside the tuberculin skin test in order to detect Mycobacterium bovis
      infected cattle. The performance of the IFNgamma test has been evaluated in many
      countries worldwide and wider usage as a disease surveillance tool is constrained
      due to the relatively low and inconsistent specificity at a herd and area level.
      This results in disclosure of a higher proportion of false positive reactors when
      compared with the skin test. In this study, we used cohorts of animals from low
      prevalence tuberculosis herds (n = 136) to assess a range of risk factors that
      might influence the specificity of the test. Univariate and multivariate logistic
      generalised estimating-equation (GEE) models were used to evaluate potential risk
      factors associated with a false positive IFNgamma test result. In these herds,
      the univariate model revealed that the region of herd origin, the time of year
      when the testing was carried out, and the age of the animal were all significant
      risk factors. In the final multivariate models only animal age and region of herd
      origin were found to be significant risk factors. A high proportion of herds with
      multiple IFNgamma false positive animals were located in one county, with
      evidence of within-herd clustering, suggesting a localised source of non-specific
      sensitization. Knowledge of the underlying factors influencing the IFNgamma test
      specificity could be used to optimize the test performance in different disease
      level scenarios in order to reduce the disclosure rate of false positive
      reactors.

PMID- 24308749
TI  - Training for complex endoscopic procedures: how to incorporate endoscopic
      submucosal dissection skills in the West?
AB  - Endoscopic submucosal dissection (ESD) has been employed for removal of early
      neoplastic gastrointestinal lesions and has well-documented higher en bloc and
      curative resection rates compared with endoscopic mucosal resection. Based on
      these advantages, ESD has gained widespread use in Asia but unfortunately not in
      the West. The main obstacles remain the very flat learning curve and lack of
      training resources. In Asia, ESD skills are acquired in the time-honored
      mentor/apprentice model over a period of few years. This algorithm cannot be
      directly applied in the West due to substantial differences. Can we train Western
      endoscopists in ESD in a model that bridges the gap between the traditional
      approach that requires years to gain proficiency and the weekend crash course
      approach that does not do justice to our patients? We propose a training
      algorithm that would guide the ESD training of Western endoscopists in a way to
      reliably deliver high-quality end product. 

PMID- 24308748
TI  - Association of HLA-B*51:01 with papillary thyroid carcinoma in the Chinese Han
      population of the Shandong coastal areas.
AB  - BACKGROUND: A lot of work has been done to study the association between human
      leukocyte antigen (HLA) and papillary thyroid carcinoma (PTC) in various
      populations. But the results of the currently available studies are not
      consistent. The aim of this study was to evaluate the association of HLA-A, -B, 
      C, -DRB1, and -DQB1 with PTC in the Chinese Han population of the coastal areas
      of Shandong Province with respect to age and sex. METHODS: A total of 154
      patients diagnosed with PTC were analyzed for HLA-A, -B, -C, -DRB1, and -DQB1
      alleles by using a polymerase chain reaction sequence-based typing (PCR-SBT)
      method. Two hundred unrelated healthy individuals were typed as controls.
      RESULTS: Compared with the controls, the HLA-B*51:01 (8.8% vs. 4.5%, p=0.029, OR
      2.039 [CI 1.101-3.775]) and HLA-C*07:06 (2.6% vs. 0.5%, p=0.024, OR 5.307 [CI
      1.119-25.171]) allele frequencies were higher in the PTC patients, while the HLA
      C*07:01 (1.3% vs. 6.0%, p=0.001, OR 0.206 [CI 0.071-0.601]) allele frequency was
      lower in the PTC patients that did not persist after Bonferroni correction for
      multiple tests. This showed no statistically significant correlation of the HLA
      A, -DRB1, and -DQB1 alleles and PTC. The incidence of PTC was more frequent in
      females between 30 and 60 years old. There were no significant differences in the
      age and sex distributions between the total and the HLA-B*51:01 positive PTC
      patients. CONCLUSIONS: The HLA associations in this Chinese Han population differ
      markedly from studies done in Europeans and Caucasians. The results reveal that
      HLA-B*51:01 is more likely to be a susceptible allele for PTC in addition to age
      and sex in the coastal areas of Shandong Province.

PMID- 24308750
TI  - Advanced endoscopic resection in the colon: recent innovations, current
      limitations and future directions.
AB  - The major health burden of colorectal cancer is reduced by colonoscopic
      polypectomy. The majority of polyps encountered are diminutive in size and easily
      removed; however, endoscopic removal of lesions >20 mm in size is also effective
      and safe. Techniques have progressed, advancing the boundaries of endoscopic
      therapy to include resection of circumferential lesions and selected submucosal
      invasive cancers. While there are cost and safety advantages over surgical
      management, specific limitations of endoscopic resection remain, chiefly
      bleeding, perforation and recurrence. Recent studies highlight the utility of
      risk stratification and demonstrate the effectiveness of endoscopic treatment of
      complications; however, strategies for prevention remain elusive. Prediction of
      submucosal invasive cancers through systematic assessment of lesion morphology
      and surface pattern is now established. Harnessing submucosal invasive cancer
      prediction and risk stratification allows a shift toward lesion-specific therapy,
      the next paradigm in the management of advanced colonic lesions. 

PMID- 24308751
TI  - Genotypic characteristics of Mycobacterium tuberculosis isolated from household
      contacts of tuberculosis patients in the Philippines.
AB  - BACKGROUND: The Philippines has an extremely high rate of tuberculosis but little
      is known about M. tuberculosis genotypes and transmission dynamics in this
      country. The aim of this study was to determine the proportion of household
      contacts who develop active TB due to direct transmission from an index case in
      that household. METHODS: Mycobacterium tuberculosis isolates from household
      contacts of tuberculosis patients in the Philippines were characterized using
      restriction-fragment-length polymorphism analysis, spoligotyping, and
      mycobacterial interspersed repetitive units - variable number tandem repeats
      typing (12-loci) to determine their utility in elucidating transmission in an
      area of high tuberculosis prevalence. Drug susceptibility patterns for these
      isolates were also determined. RESULTS: Spoligotyping and MIRU-VNTR typing
      results matched in 10 (62.5%) of 16 index patient-household contact pairs while
      IS6110 fingerprints matched in only six (37.5%) pairs. Only 3/16 (18.8%) index
      patient-household contact pairs had identical drug susceptibility results.
      CONCLUSIONS: Strain typing of M. tuberculosis isolates from household contacts in
      the Philippines indicates that transmission of strains does not necessarily occur
      directly from the index patient living in close proximity in the same household
      but rather that community-based transmission also frequently occurs. Accurate
      susceptibility testing of all isolates is necessary to insure optimal care of
      both the index patients and any culture-positive household contacts.

PMID- 24308752
TI  - Health-related quality of life in patients with polycystic ovary syndrome (PCOS):
      a model-based study of predictive factors.
AB  - INTRODUCTION: Understanding the factors that contribute to health-related quality
      of life (HRQOL) is critical for developing the most appropriate interventions for
      improving or maintaining the HRQOL in polycystic ovary syndrome (PCOS) patients.
      AIM: This study sought to determine the most significant predictors of the HRQOL
      in patients with PCOS. METHODS: This was a cross-sectional study of 300 women
      with PCOS that was carried out in Kashan, Iran. A sample of women with PCOS was
      entered into the study and completed the following questionnaires: the Hospital
      Anxiety and Depression Scale, the Body Image Concern Inventory (BICI), the
      Rosenberg's Self-Esteem Scale score, the modified polycystic ovary syndrome
      health-related quality of life questionnaire, the Female Sexual Function Index.
      MAIN OUTCOME MEASURE: Both direct and indirect relationships among clinical
      severity, psychological status, self-esteem, body image, and sexual function as
      independent predictors of HRQOL were examined using structural equation modeling
      (SEM) analysis. By using the SEM, we simultaneously test a number of possible
      hypotheses concerning the interrelations among the predictors of HRQOL in PCOS
      patients. RESULTS: In relation with severity of PCOS, reproductive history and
      menstrual status explained a high proportion of the variance of clinical
      variables (factor loading 0.37 and 0.34, respectively). The highest effect on
      HRQL was exerted by indirect effect of clinical factor (beta = 0.90), self-esteem
      (beta = 1.12), body image (beta = 1.06), and sexual function (beta = 0.26) that
      influenced negatively HRQOL. The infertility and menstrual domains were the most
      affected areas of HRQOL. In relation with sexual dysfunction, the most affected
      domains were desire and arousal. CONCLUSION: The highest effect of PCOS symptoms
      on HRQOL impairment among patients was exerted by self-esteem, body image, and
      sexual dysfunction. With regard to HRQOL in clinical routine, we conclude these
      mediating factors should be taken into consideration and adequately treated if
      present.

PMID- 24308754
TI  - Serum levels of interleukin-22 and hepatitis B core-related antigen are
      associated with treatment response to entecavir therapy in chronic hepatitis B.
AB  - AIM: We sought to clarify the associations between serum cytokines and
      chemokines, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen
      (HBcrAg), and hepatitis B virus (HBV) DNA and response to entecavir therapy in
      chronic hepatitis B. METHODS: We analyzed six cytokines (interleukin [IL]-2, IL
      6, IL-10, IL-12p70, IL-21 and IL-22) and five chemokines (CCL2, CCL3, CXCL9,
      CXCL10 and CXCL11) before and at 6, 12 and 24 months during entecavir therapy in
      48 chronic hepatitis B patients. Quantitative measurement of HBsAg, HBcrAg and
      HBV DNA was performed. A virological response (VR) was defined as serum HBV DNA
      of less than 2.1 log copies/mL by treatment month 24. RESULTS: Thirty-nine
      patients (81%) achieved a VR. Serum IL-6 (P = 0.031), CXCL-9 (P = 0.002), and
      CXCL-10 (P = 0.001) were high in chronic HBV and correlated positively with
      transaminases and bilirubin. Before treatment, elevated IL-22 (P = 0.031) and
      lower HBsAg (P = 0.001) and HBcrAg (P < 0.001), but not HBV DNA, were associated
      with a favorable treatment outcome. In multivariate analysis, high IL-22 (hazard
      ratio = 13.67, P = 0.046) and low HBcrAg (hazard ratio = 10.88, P = 0.048) were
      independently associated with a VR. The levels of IL-22 (P < 0.001), HBsAg (P <
      0.001), and HBcrAg (P < 0.001) all decreased from baseline to 24 months of
      treatment in virological responders. CONCLUSION: Serum IL-22 and HBcrAg are
      predictive markers of a VR to entecavir therapy in patients with chronic
      hepatitis B.

PMID- 24308753
TI  - Functional clustering of the human inferior parietal lobule by whole-brain
      connectivity mapping of resting-state functional magnetic resonance imaging
      signals.
AB  - The human inferior parietal lobule (IPL) comprised the lateral bank of the
      intraparietal sulcus, angular gyrus, and supramarginal gyrus, defined on the
      basis of anatomical landmarks and cytoarchitectural organization of neurons.
      However, it is not clear as to whether the three areas represent functional
      subregions within the IPL. For instance, imaging studies frequently identified
      clusters of activities that cut across areal boundaries. Here, we used resting
      state functional magnetic resonance imaging (fMRI) data to examine how individual
      voxels within the IPL are best clustered according to their connectivity to the
      whole brain. The results identified a best estimate of seven clusters that are
      hierarchically arranged as the anterior, middle, and posterior subregions. The
      anterior, middle, and posterior IPL are each significantly connected to the
      somatomotor areas, superior/middle/inferior frontal gyri, and regions of the
      default mode network. This functional segregation is supported by recent
      cytoarchitechtonics and tractography studies. IPL showed hemispheric differences
      in connectivity that accord with a predominantly left parietal role in tool use
      and language processing and a right parietal role in spatial attention and
      mathematical cognition. The functional clusters may also provide a more
      parsimonious and perhaps even accurate account of regional activations of the IPL
      during a variety of cognitive challenges, as reported in earlier fMRI studies.

PMID- 24308755
TI  - The novel ss469415590 variant predicts virological response to therapy in
      patients with chronic hepatitis C virus type 1 infection.
AB  - BACKGROUND: A novel dinucleotide variant TT/?G (ss469415590) has been associated
      with hepatitis C virus clearance. AIM: To assess the role of the ss469415590
      variant, compared with the known IL28B polymorphisms (rs8099917, rs12979860 and
      rs12980275) for predicting virological response to therapy in chronic hepatitis
      C, and its association with the CXCL10 chemokine serum levels - a surrogate
      marker of interferon-stimulated genes activation. METHODS: Multivariate analysis
      of factors predicting rapid and sustained virological response in 280
      consecutive, treatment-naive, nondiabetic, Caucasian patients with chronic
      hepatitis C treated with peginterferon alpha and ribavirin. RESULTS: In hepatitis
      C virus genotype 1, the OR (95% CI) for rapid and sustained virological response
      for the wild-type ss469415590 TT was 9.88 (1.99-48.99) and 7.25 (1.91-27.51),
      respectively, similar to those found for rs12979860 CC [9.55 (1.93-47.37) and
      6.30 (1.71-23.13)] and for rs12980275 AA [9.62 (1.94-47.77] and 7.83 (2.02
      30.34)], but higher than for rs8099917 TT [4.8 (1.73-13.33) and 4.75 (2.05
      10.98)]. In hepatitis C virus genotype 1, mean (SD) CXCL10 levels in patients
      with the TT/TT, TT/?G and ?G/?G variants were, respectively, 355.1 (240.6), 434.4
      (247.4) and 569.9 (333.3) (P = 0.04). In patients with genotypes 2 and 3 no
      significant association was found for TT/?G with viral response. The predictive
      value of ss469415590 was stronger in patients with advanced fibrosis.
      CONCLUSIONS: The novel IL28B variants at marker ss469415590 predict response to
      IFN alpha in chronic hepatitis C patients, especially in those with advanced
      fibrosis. Their determination may be superior to that of known IL28B variants for
      patient management using IFN-based regimens.

PMID- 24308756
TI  - Agonistic anti-human Fas monoclonal antibody induces fibroblast-like synoviocyte
      apoptosis in haemophilic arthropathy: potential therapeutic implications.
AB  - Haemophilic arthropathy (HA) is characterized by chronic proliferative synovitis
      leading to cartilage destruction and shares some pathological features with
      rheumatoid arthritis (RA). Apoptosis has been implicated in RA pathogenesis, and
      an agonistic anti-Fas monoclonal antibody (mAb) was found to induce RA fibroblast
      like synoviocyte (FLS) apoptosis and suppress synovial hyperplasia in animal
      models of RA. The aim of this study was to evaluate the effect of anti-Fas mAb on
      HA-FLS. FLS were isolated from knee synovial biopsies from six HA patients, six
      RA patients and six healthy subjects. The expression of Fas in synovial biopsies
      was investigated by immunohistochemistry. FLS were stimulated with anti-Fas mAb
      at different concentrations, alone or in combination with tumour necrosis factor
      alpha (TNF-alpha) and basic fibroblast growth factor (bFGF). Fas expression in
      FLS was assessed by Western blot. Cell viability was studied with the WST-1
      assay. Active caspase-3 levels were measured using ELISA and Western blot. A
      strong Fas-immunoreactivity was observed in different cells of HA synovium,
      including FLS, inflammatory cells and endothelial cells. Fas antigen was
      constitutively overexpressed in cultured HA-FLS. Anti-Fas mAb had a significant
      cytotoxicity on HA-FLS in a dose-dependent manner, either alone or in combination
      with TNF-alpha and bFGF. These cytotoxic effects were due to the ability of anti
      Fas to induce HA-FLS apoptosis, as shown by the increased active caspase-3
      levels. Anti-Fas mAb exhibited a more pronounced pro-apoptotic effect on HA-FLS
      than RA-FLS. Fas antigen is highly expressed on HA-FLS and its stimulation by
      anti-Fas mAb may be an effective strategy to induce HA-FLS apoptosis. 

PMID- 24308757
TI  - Response to comment on "solid recovered fuel: materials flow analysis and fuel
      property development during the mechanical processing of Biodried waste".

PMID- 24308758
TI  - Tumor necrosis factor and interleukin-6 gene polymorphisms and endometriosis risk
      in Asians: a systematic review and meta-analysis.
AB  - A relationship between endometriosis and tumor necrosis factor (TNF-alpha) and
      interleukin-6 (IL-6) gene polymorphisms has been raised for Asians. However, this
      topic is controversial. This study was a meta-analysis to explore whether TNF
      alpha/IL-6 gene polymorphisms were associated with a risk of endometriosis in
      Asians. By searching PubMed, HuGENet, and China National Knowledge Infrastructure
      (CNKI) databases, 17 studies were identified and included (3372 cases and 4008
      controls). The odds ratio (OR) with 95% confidence interval (CI) was used to
      assess the association between TNF-alpha/IL-6 gene polymorphisms and
      endometriosis risk. An association of TNF-alpha gene -1031T/C polymorphism with
      endometriosis was found (TT + TC vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 37.1%,
      P = 0.20; TT vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 43.0%, P = 0.173; TC vs.
      CC: OR 0.49, 95% CI 0.29-0.83, I(2) = 10.6%, P = 0.327). In addition, TNF-alpha
      238A/G and IL-6 -174C/G gene polymorphisms were also likely to be associated with
      endometriosis in Asians. For the TNF-alpha-238A/G gene polymorphism, the OR was
      1.577 (95% CI: 1.01-2.48). For the IL-6 -174C/G gene polymorphism, the OR was
      1.554 (95% CI: 1.04-2.31). No associations were detected between the TNF-alpha
      308A/G and IL-6 -634C/G polymorphisms and susceptibility to endometriosis. Our
      results indicate that the TNF-alpha gene -1031T/C polymorphism can reduce the
      risk of endometriosis, but for Asians, TNF-alpha-238A/G and IL-6 -174C/G gene
      polymorphisms may be a risk factor for endometriosis. No association was found
      for the TNF-alpha-308A/G and IL-6 -634C/G gene polymorphisms. 

PMID- 24308760
TI  - Synthesis of functionalized cyclic boronates.
AB  - Deprotonation of a simple borylated allylic sulfone and subsequent alkylation
      with certain unsaturated electrophiles provide substrates that are easily
      converted into functionalized alkenyl boronates with ring sizes from five- to
      seven-membered. A Chan-Lam reaction on one such substrate afforded an
      alkoxyallylic sulfone that was readily converted via a (4 + 3)-cycloaddition to a
      polycycle possessing the ABC ring substructure of ingenol. 

PMID- 24308759
TI  - Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for
      patients with chronic, low back pain: 24-month results of a prospective
      multicenter study.
AB  - OBJECTIVE: The aim of this study was to investigate the long-term efficacy and
      safety of paresthesia-free high-frequency spinal cord stimulation (HF10 SCS) for
      the treatment of chronic, intractable pain of the low back and legs. DESIGN:
      Prospective, multicenter, observational study. METHOD: Patients with significant
      chronic low back pain underwent implantation of a spinal cord stimulator capable
      of HF10 SCS. Patients' pain ratings, disability, sleep disturbances, opioid use,
      satisfaction, and adverse events were assessed for 24 months. RESULTS: After a
      trial period, 88% (72 of 82) of patients reported a significant improvement in
      pain scores and underwent the permanent implantation of the system. Ninety
      percent (65 of 72) of patients attended a 24-month follow-up visit. Mean back
      pain was reduced from 8.4 +/- 0.1 at baseline to 3.3 +/- 0.3 at 24 months (P <
      0.001), and mean leg pain from 5.4 +/- 0.4 to 2.3 +/- 0.3 (P < 0.001).
      Concomitantly to the pain relief, there were significant decreases in opioid use,
      Oswestry Disability Index score, and sleep disturbances. Patients' satisfaction
      and recommendation ratings were high. Adverse Events were similar in type and
      frequency to those observed with traditional SCS systems. CONCLUSIONS: In
      patients with chronic low back pain, HF10 SCS resulted in clinically significant
      and sustained back and leg pain relief, functional and sleep improvements, opioid
      use reduction, and high patient satisfaction. These results support the long-term
      safety and sustained efficacy of HF10 SCS.

PMID- 24308761
TI  - Cytomegalovirus infection in pediatric allogenic hematopoietic stem cell
      transplantation. A single center experience.
AB  - We report a retrospective analysis of Cytomegalovirus (CMV) infection: incidence,
      recurrence, resistance, and subsequent disease of 81 children who underwent
      allogenic hematopoietic stem cell transplantation (HSCT). The recipient and/or
      donor's CMV serology was positive prior to transplant [recipient (R+) and/or
      donor (D+)]. CMV was monitored by RT-PCR starting from the first week post
      transplant. Forty patients showed CMV infection (49, 5%). Of them 10 manifested
      CMV disease leading to four deaths. In univariate analysis, factors associated
      with CMV infection were CMV R+ P < .01, CMV R+/D+ pair P < .01, nonbone marrow
      (BM) stem cell source P < .05, nonirradiation conditioning regimen P < .05,
      Antithymocyte globulin (ATG) P < .01. Factors associated with CMV resistance
      were: >1 HLA allele mismatch P < .05, CMV R +/D-pair P < .01, CMV D-P < .01, non
      BM P < .05, nongenoidentical transplant P < .01. CMV disease was influenced by >1
      HLA allele mismatch (P < .001), non-BM (P < .01). On multivariate analysis, CMV
      R+/D- (P < .05), corticosteroids >=2 mg/kg P < .01, ATG P < .01 and non-BM (P <
      .05) were independent factors for CMV infection. CMV R+ transplant is associated
      with more CMV infection and resistance to preemptive treatment. Prolonged immune
      suppression (IS) worsens outcome of CMV infection and should be shortened
      whenever possible. 

PMID- 24308762
TI  - XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell
      lines by inhibiting Wnt/beta-catenin signaling pathway.
AB  - BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in
      childhood. The present treatment including surgery, chemotherapy and radiation,
      which have only 40% long-term cure rates, and usually cause tumor recurrence.
      Thus, looking for new effective and less toxic therapies has important
      significance. XAV939 is a small molecule inhibitor of tankyrase 1(TNKS1). The
      objective of this study is to investigate the effect of XAV939 on the
      proliferation and apoptosis of NB cell lines, and the related mechanism. METHODS:
      In the present study, we used both XAV939 treatment and RNAi method to
      demonstrate that TNKS1 inhibition may be a potential mechanism to cure NB. MTT
      method was used for determining the cell viability and the appropriate
      concerntration for follow-up assays. The colony formation assay, Annexin V
      staining and cell cycle analysis were used for detecting colony forming ability,
      cell apoptosis and the percentage of different cell cycle. The Western blot was
      used for detecting the expression of key proteins of Wnt/ beta-catenin (Wnt/beta
      catenin) signaling pathway. RESULTS: The results showed that TNKS1 inhibition
      decreased the viability of SH-SY5Y, SK-N-SH and IMR-32 cells, induced apoptosis
      in SH-SY5Y as well as SK-N-SH cells, and led to the accumulation of NB cells in
      the S and G2/M phase of the cell cycle. Moreover, we demonstrated TNKS1
      inhibition may in part blocked Wnt/beta-catenin signaling and reduced the
      expression of anti-apoptosis protein. Finally, we also demonstrated that TNKS1
      inhibition decreased colony formation in vitro. CONCLUSIONS: These findings
      suggested that TNKS1 may be a potential molecule target for the treatment of NB.

PMID- 24308763
TI  - Domestic violence and its predictors among married women in reproductive age in
      Fagitalekoma Woreda, Awi zone, Amhara regional state, North Western Ethiopia.
AB  - BACKGROUND: Violence against women is one of the most systematic and prevalent
      human rights abuses in the world. It is a form of discrimination and deeply
      rooted in power imbalances and structural inequality between women and men.
      Documenting the extent of the problem and associated factors is essential to
      develop public health interventions to tackle violence against women. Therefore,
      the objective of this study was to determine magnitude of domestic violence and
      identify its predictors among married women in the reproductive age in north
      western Ethiopia. METHODS: Community-based cross-sectional study was conducted
      from February 15 to March 15, 2011 among 682 married women and 46 key informants.
      Systematic sampling technique was used to select respondents for the quantitative
      method. Purposive sampling was used to select in-depth interview key informants
      for and focus group discussants. Data were analyzed using SPSS window version
      16.0. Binary logistic regression and multivariable logistic regression analysis
      were carried out to determine the prevalence and identify independent predictors
      of domestic violence against women. Statistical association was measured by
      adjusted odds ratios and 95% confidence intervals. Statistical significance was
      declared at P < 0.05. RESULT: The prevalence of domestic violence was 78.0%.
      About 73.3%, 58.4% and 49.1% of women reported different forms of psychological,
      physical and sexual violence, respectively. Alcohol consumption by husband (AOR =
      1.9, 95%CI = 1.3, 2.8), being pregnant (AOR = 2.1, 95% CI = 1.4, 3.4), decision
      making power (AOR = 2.3, 95% CI = 1.5, 3.4) and annual income (AOR = 1.9, 95% CI
      = 1.1, 3.3) were predictors of domestic violence. CONCLUSION: The prevalence of
      domestic violence was very high as compared to other studies. Women's husband
      alcohol consumption, decision making power annual household income and being
      pregnant are some of the predictors of domestic violence against women.

PMID- 24308764
TI  - Operational definitions of successful aging: a systematic review.
AB  - BACKGROUND: Half a century after the inception of the term "successful aging
      (SA)," a consensus definition has not emerged. The current study aims to provide
      a comprehensive snapshot of operational definitions of SA. METHODS: A systematic
      review across MedLine, PsycInfo, CINAHL, EMBASE, and ISI Web of Knowledge of
      quantitative operational definitions of SA was conducted. RESULTS: Of the 105
      operational definitions, across 84 included studies using unique models, 92.4%
      (97) included physiological constructs (e.g. physical functioning), 49.5% (52)
      engagement constructs (e.g. involvement in voluntary work), 48.6% (51) well-being
      constructs (e.g. life satisfaction), 25.7% (27) personal resources (e.g.
      resilience), and 5.7% (6) extrinsic factors (e.g. finances). Thirty-four
      definitions consisted of a single construct, 28 of two constructs, 27 of three
      constructs, 13 of four constructs, and two of five constructs. The operational
      definitions utilized in the included studies identify between <1% and >90% of
      study participants as successfully aging. CONCLUSIONS: The heterogeneity of these
      results strongly suggests the multidimensionality of SA and the difficulty in
      categorizing usual versus successful aging. Although the majority of
      operationalizations reveal a biomedical focus, studies increasingly use
      psychosocial and lay components. Lack of consistency in the definition of SA is a
      fundamental weakness of SA research.

PMID- 24308765
TI  - Caries experience in schoolchildren in Bucharest, Romania: the PAROGIM study.
AB  - OBJECTIVE: This cross-sectional study aimed to investigate the prevalence and
      experience of dental caries among children from public middle schools in
      Bucharest in relation to socioeconomic status and access to school-based dental
      care. METHODS: Clinical data were collected from 1,595 schoolchildren aged 10-17
      years, randomly allocated by clusters into a stratified sample population. The
      dental caries were scored according to the World Health Organization (WHO)
      clinical criteria and expressed based on tooth and surface levels [Decayed
      Missing-Filled Teeth/Surfaces indices (DMFT/DMFS)]. A questionnaire was
      administered to the children to determine the education level of their parents
      and their living standard. RESULTS: The caries prevalence was 75 percent, and 64
      percent had untreated caries. The mean DMFT value for the entire sample was 2.8,
      and its highest component was decayed teeth (mean DT 2). Parental education level
      had the strongest influence on the caries scores; 70 percent of children whose
      parents had not completed a university degree had untreated caries (%DT) compared
      to only 49 percent of children whose parents had a higher level of education (P <
      0.05). Children with access to school-based dental care had significantly better
      dental health (P < 0.05). CONCLUSION: Compared to previous national surveys, the
      caries rates among schoolchildren in Bucharest are slowly declining. However,
      there was still a high proportion of untreated caries with a clear socioeconomic
      gradient, and a change in the school-based oral preventive strategy is needed to
      meet the needs of the children.

PMID- 24308766
TI  - Interprofessional education in primary care for the elderly: a pilot study.
AB  - BACKGROUND: The Dutch health care system faces huge challenges with regard to the
      demand on elderly care and the competencies of nurses and physicians required to
      meet this demand.At present, the main focus of health care in the Netherlands
      lies on illness and treatment. However, (frail) elderly need care and support
      that takes their daily functioning and well-being into consideration as well.
      Therefore, health care professionals, especially those professionals working in
      primary care such as GPs and practice nurses, will be challenged to a paradigm
      shift in emphasis from treating illness to promoting health (healthy ageing).
      Interprofessional education is necessary to realise this shift in professional
      behaviour. Evidence indicates that interprofessional education (IPE) can play a
      pivotal role in enhancing the competencies of professionals in order to provide
      elderly care that is both effectively, integrated and well-coordinated. At
      present, however, IPE in primary care is rarely utilised in the Netherlands.
      Therefore, the aim of this pilot study was to develop an IPE program for GPs and
      practice nurses and to evaluate the feasibility of an IPE program for
      professionals with different educational backgrounds and its effect on the
      division of professionals' tasks and responsibilities. METHODS: Ten GPs and 10
      practice nurses from eight primary care practices in two provinces in the north
      of the Netherlands, Groningen and Drenthe (total population about 1.1 million
      people), participated in the pilot IPE program. A mixed methods design including
      quantitative and qualitative methods was used to evaluate the IPE program.
      RESULTS: During the program, tasks and responsibilities, in particular those
      related to the care plan, shifted from GP to practice nurse. The participants'
      attitude toward elderly (care) changed and the triage instrument, the practical
      tool for prioritising preferences of the elderly and discussing their medication
      use, was considered to have an added value to the development of the care plan.
      CONCLUSIONS: The results of this pilot study show that an interprofessional
      education program for professionals with different educational backgrounds (GPs
      and practice nurses) is feasible and has an added value to the redefining of
      tasks and responsibilities among GPs and practice nurses.

PMID- 24308767
TI  - Recurrent spontaneous abortions, Hashimoto thyroiditis and alopecia totalis:
      response to anticoagulation and intravenous immunoglobulin therapy.
AB  - INTRODUCTION: Although numerous studies indicated a link between antithyroid
      antibodies and recurrent spontaneous abortions (RSA), consensus on the treatment
      of this condition is still lacking. CASE REPORT: We present a case of a 35-year
      old pregnant woman (gestation week 4) with primary hypothyroidism, total
      alopecia, high level of positive antithyroid antibodies, and history of two
      recurrent spontaneous abortions in early pregnancy. Along with L-thyroxin
      substitution, intravenous human immunoglobulin (IVIg) combined with
      anticoagulation and antiaggregation therapy was introduced. During pregnancy her
      scalp hair completely re-grew, and following gestation week 39 she delivered
      healthy female child. CONCLUSION: Thyroid antibodies could contribute to previous
      recurrent abortions in our patient. It is suggested that in older primiparas with
      Hashimoto thyroiditis and history of RSA, a combined treatment with IVIg,
      anticoagulation and antiaggregation therapy should be considered.

PMID- 24308768
TI  - Protection from cyclophosphamide-induced ovarian damage with bone marrow-derived
      mesenchymal stem cells during puberty.
AB  - OBJECTIVE: In female cancer survivors, the accelerated loss of primordial
      follicles may lead to premature ovarian failure. We investigated the protective
      effects of bone marrow derived mesenchymal stem cells (BMMSC) and gonadotropin
      releasing hormone analogue (GnRHa) against chemotherapeutic-induced ovarian
      toxicity in a rat model. MATERIAL AND METHODS: Forty-eight Wistar albino female
      rats were divided into four groups. Group 1 was composed of rats that were given
      200 mg/kg cyclophosphamide injection for each cycle (two cycles for each rat).
      Both cyclophosphamide and 0.4 ug GnRHa were administered to Group 2.
      Cyclophosphamide and 4 million/kg BMMSC were administered to Group 3.
      Cyclophosphamide, GnRHa, and BMMSC were administered to Group 4. Germ cell
      apoptosis, DNA fragmentation and primordial follicular count were investigated
      with Cleave Caspase-9 and TUNEL analysis. The presence of the SRY gene on the Y
      chromosome in the ovary of the recipient female rats was checked with PCR.
      RESULTS: Immunohistochemical staining (IHS) of Caspase-9 and TUNEL was higher in
      Group 1 than in Group 3 (p < 0.05). Similarly, Group 4 had higher values than
      Group 3 (p < 0.05). The presence of the SRY gene was detected in Groups 3 and 4
      with the PCR analysis. The mean primordal follicle count was lowest in Group 1
      and the mean primordial follicle counts were higher in Groups 2 and 3 than in
      Group 1. The difference between Group 1 and Group 4 was not significant.
      CONCLUSION: BMMSC therapy was found to be protective from germ cell apoptosis and
      DNA damage when it was used with chemotherapy regimens including alkylating
      agents.

PMID- 24308770
TI  - The Partner's presence in the sex research lab differentially affects sexual
      arousal in women and men.
AB  - INTRODUCTION: The present study addressed the ecological validity of the
      individual-focused experimental paradigm in sex research. AIM: The aim of this
      study was to investigate the effect of partner presence vs. absence in the
      laboratory testing situation, and of manipulation of attentional focus, on
      genital and subjective sexual arousal of healthy women and men. METHODS: Sexually
      functional heterosexual men (n = 12) and women (n = 12) and their partners
      participated in this study. During partner presence, the partner sat opposite to
      the participant; self-focused attention was experimentally manipulated by
      introducing, respectively, a semi-reflecting glass pane, and a wall-mounted
      camera. MAIN OUTCOME MEASURES: Perceived state self-focused attention and genital
      and subjective sexual arousal during presentation of audiovisual erotic film
      stimuli were assessed. RESULTS: Partner presence resulted in higher perceived
      self-focus (eta(p)(2) = 0.22) and lower genital responses to erotic stimulation
      (eta(p)(2) = 0.21). The interaction of partner presence and increased self
      focused attention differentially affected genital arousal in female and male
      participants (eta(p)(2) = 0.38). The mean genital response in men was lower
      during private self-focus than during non-self-focus with the partner present but
      was higher during private self-focus with the the partner absent (eta(p)(2) =
      0.23). The genital response in women to public self-focus was lower than to
      private self-focus and to non-self-focus with their partner present (eta(p)(2) =
      0.36). With the partner absent, the genital response in women to private self
      focus was lower than to non-self-focus (eta(p)(2) = 0.23). Retrospective
      subjective arousal of women was higher with partner present (M = 3.2) than with
      partner absent (M = 2.9), whereas men reported higher retrospective subjective
      arousal with their partner absent (M = 3.5) than present (M = 3.1). CONCLUSIONS:
      These findings suggest that mere presence of the partner impacts the sexual
      response differentially in women and men. Enhancing the ecological validity of
      the individual-based laboratory paradigm for sex research warrants closer
      examination in future research.

PMID- 24308769
TI  - Comparison of population iodine estimates from 24-hour urine and timed-spot urine
      samples.
AB  - BACKGROUND: Median urine iodine concentration (UIC; MUg/L) in spot urine samples
      is recommended for monitoring population iodine status. Other common measures are
      iodine:creatinine ratio (I/Cr; MUg/g) and estimated 24-hour urine iodine
      excretion (UIE; I/Cr * predicted 24-hour Cr; MUg/day). Despite different units,
      these measures are often used interchangeably, and it is unclear how they compare
      with the reference standard 24-hour UIE. METHODS: Volunteers aged 18-39 years
      collected all their urine samples for 24 hours (n=400). Voids from morning,
      afternoon, evening, overnight, and a composite 24-hour sample were analyzed for
      iodine. We calculated median observed 24-hour UIE and 24-hour UIC, and spot UIC,
      I/Cr, and two measures of estimated UIE calculated using predicted 24-hour Cr
      from published estimates by Kesteloot and Joosens (varies by age and sex) and
      published equations by Mage et al. (varies by age, sex, race, and anthropometric
      measures). We examined mean differences and relative difference across iodine
      excretion levels using Bland-Altman plots. RESULTS: Median 24-hour UIE was 173.6
      MUg/day and 24-hour UIC was 144.8 MUg/L. From timed-spot urine samples, estimates
      were: UIC 147.3-156.2 MUg/L; I/Cr 103.6-114.3 MUg/g, estimated 24-hour UIE
      (Kesteloot and Joosens) 145.7-163.3 MUg/day; and estimated 24-hour UIE (Mage)
      176.5-187.7 MUg/day. Iodine measures did not vary consistently by timing of spot
      urine collection. Compared with observed 24-hour UIE, on average, estimated
      (Mage) 24-hour UIE was not significantly different, while estimated 24-hour UIE
      (Kesteloot and Joosens) was significantly different for some ethnicity/sex
      groups. Compared with 24-hour UIC, on average, spot UIC did not differ.
      CONCLUSIONS: Estimates of UIC, I/Cr, and estimated 24-hour UIE (I/Cr * predicted
      24-hour Cr) from spot urine samples should not be used interchangeably. Estimated
      24-hour UIE, where predicted 24-hour Cr varies by age, sex, ethnicity, and
      anthropometric measures and was calculated with prediction equations using data
      from the sample, was more comparable to observed 24-hour UIE than when predicted
      24-hour Cr was from published estimates from a different population. However,
      currently no cutoffs exist to interpret population estimated 24-hour UIE values.

PMID- 24308771
TI  - Asymmetric van der Waals forces drive orientation of compositionally anisotropic
      nanocylinders within smectic arrays: experiment and simulation.
AB  - Understanding how micro- and nanoparticles interact is important for achieving
      bottom-up assembly of desired structures. Here, we examine the self-assembly of
      two-component, compositionally asymmetric nanocylinders that sediment from
      solution onto a solid surface. These particles spontaneously formed smectic
      arrays. Within the rows of an array, nanocylinders tended to assemble such that
      neighboring particles had the same orientation of their segments. As a probe of
      interparticle interactions, we classified nanocylinder alignments by measuring
      the segment orientations of many sets of neighboring particles. Monte Carlo
      simulations incorporating an exact expression for the van der Waals (vdW) energy
      indicate that differences in the vdW interactions, even when small, are the key
      factor in producing observed segment alignment. These results point to
      asymmetrical vdW interactions as a potentially powerful means of controlling
      orientation in multicomponent cylinder arrays, and suggest that designing for
      these interactions could yield new ways to control self-assembly. 

PMID- 24308772
TI  - Experimental infection with equine herpesvirus type 1 (EHV-1) induces
      chorioretinal lesions.
AB  - Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating
      manifestations of equine herpesvirus type 1 (EHV-1) infection but our
      understanding of its pathogenesis remains rudimentary, partly because of a lack
      of adequate experimental models. EHV-1 infection of the ocular vasculature may
      offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in
      a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may
      be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and
      to determine the frequency of ocular EHV-1, our goal was to study: (1)
      Dissemination of virus following acute infection, (2) Development and frequency
      of ocular lesions following infection, and (3) Utility of a GFP-expressing virus
      for localization of the virus in vivo. Viral antigen could be detected following
      acute infection in ocular tissues and the central nervous system (experiment 1).
      Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90%
      (experiment 2) and 50% (experiment 3) of experimentally infected horses, however
      ocular lesions did not appear in vivo until between 3 weeks and 3 months post
      infection. Taken together, the timing of the appearance of lesions and their
      ophthalmoscopic features suggest that their pathogenesis may involve ischemic
      injury to the chorioretina following viremic delivery of virus to the eye,
      mirroring the vascular events that result in EHM. In summary, we show that the
      frequency of ocular EHV-1 is 50-90% following experimental infection making this
      model attractive for testing future vaccines or therapeutics in an
      immunologically relevant age group.

PMID- 24308773
TI  - Molecular epidemiology of coagulase-negative Staphylococcus carriage in neonates
      admitted to an intensive care unit in Brazil.
AB  - BACKGROUND: Nasal colonization with coagulase-negative Staphylococcus (CoNS) has
      been described as a risk factor for subsequent systemic infection. In this study,
      we evaluated the genetic profile of CoNS isolates colonizing the nares of
      children admitted to a neonatal intensive care unit (NICU). METHODS: We assessed
      CoNS carriage at admittance and discharge among newborns admitted to a NICU from
      July 2007 through May 2008 in one of the major municipalities of Brazil. Isolates
      were screened on mannitol salt agar and tryptic soy broth and tested for
      susceptibility to antimicrobials using the disc diffusion method. Polymerase
      chain reaction (PCR) was used to determine the species, the presence of the mecA
      gene, and to perform SCCmec typing. S. epidermidis and S. haemolyticus isolated
      from the same child at both admission and discharge were characterized by PFGE.
      RESULTS: Among 429 neonates admitted to the NICU, 392 (91.4%) had nasal swabs
      collected at both admission and discharge. The incidence of CoNS during the
      hospitalization period was 55.9% (95% confidence interval [CI]: 50.9-60.7). The
      most frequently isolated species were S. haemolyticus (38.3%) and S.epidermidis
      (38.0%). Multidrug resistance (MDR) was detected in 2.2% and 29.9% of the CoNS
      isolates, respectively at admittance and discharge (p = 0.053). The mecA gene was
      more prevalent among strains isolated at discharge (83.6%) than those isolated at
      admission (60%); overall, SCCmec type I was isolated most frequently. The length
      of hospitalization was associated with colonization by MDR isolates (p < 0.005).
      Great genetic diversity was observed among S. epidermidis and S. haemolyticus.
      CONCLUSIONS: NICU represents an environment of risk for colonization by MDR CoNS.
      Neonates admitted to the NICU can become a reservoir of CoNS strains with the
      potential to spread MDR strains into the community.

PMID- 24308774
TI  - Systematic review with meta-analysis: non-invasive assessment of non-alcoholic
      fatty liver disease--the role of transient elastography and plasma cytokeratin-18
      fragments.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 15-40% of the
      general population. Some patients have non-alcoholic steatohepatitis (NASH) and
      progressive fibrosis, and would be candidates for monitoring and treatment. AIM:
      To review current literature on the use of non-invasive tests to assess the
      severity of NAFLD. METHODS: Systematic literature searching identified studies
      evaluating non-invasive tests of NASH and fibrosis using liver biopsy as the
      reference standard. Meta-analysis was performed for areas with adequate number of
      publications. RESULTS: Serum tests and physical measurements like transient
      elastography (TE) have high negative predictive value (NPV) in excluding advanced
      fibrosis in NAFLD patients. The NAFLD fibrosis score comprises of six routine
      clinical parameters and has been endorsed by current American guidelines as a
      screening test to exclude low-risk individuals. The pooled sensitivities and
      specificities for TE to diagnose F >= 2, F >= 3 and F4 disease were 79% and 75%,
      85% and 85%, and 92% and 92% respectively. Liver stiffness measurement often
      fails in obese patients, but the success rate can be improved with the use of the
      XL probe. A number of biomarkers have been developed for the diagnosis of NASH,
      but few were independently validated. Serum/plasma cytokeratin-18 fragments have
      been most extensively evaluated and have a pooled sensitivity of 66% and
      specificity of 82% in diagnosing NASH. CONCLUSIONS: Current non-invasive tests
      are accurate in excluding advanced fibrosis in NAFLD patients, and may be used
      for initial assessment. Further development and evaluation of NASH biomarkers are
      needed.

PMID- 24308775
TI  - Bifurcating effects of hope and support in short- and long-term health outcomes
      among primary care patients without mental illness.
AB  - RATIONALE: Adverse life events and stressors can lead to symptoms, increased
      alcohol intake, and impaired functional status, while hope and social support can
      mitigate such adverse effects. Yet, there is reason to question such simple,
      linear relationships among healthy adults. The purpose of this study was to
      assess whether short-term or long-term changes in alcohol intake, psychological
      symptoms or functional status were better modelled as cusp catastrophic or linear
      processes among primary care patients without mental illness. METHODS: This
      secondary analysis of a study on the stability of psychological symptoms among
      primary care patients without mental disorders included 38 subjects who completed
      baseline, and 2-month and/or 6-month assessments of psychological symptoms,
      functional status and stressors as well as hope and social support. The analyses
      modelled short-term and long-term changes in alcohol intake, psychological
      symptoms and functional status using cusp catastrophe (CCM) and linear modelling.
      RESULTS: Overall, four of the nine 2-month analyses found CCM superior to linear
      models; however, only one 6-month analysis (alcohol intake) found that CCM was
      superior. The 2-month cusp phenomena included both symptomatology and functional
      status. The asymmetry variables were often not significant in the CCM models; in
      fact, only distress was significant at all. While hope was a significant
      bifurcation variable at both the 2-month and 6-month levels, social support was a
      significant bifurcation variable for three of the four 2-month CCMs. CONCLUSION:
      In conclusion, while 6-month outcomes were rarely explained through CCM, half of
      2-month outcomes were. Hope and support demonstrated bifurcation effects.

PMID- 24308776
TI  - Estimating numbers of persons with persistent hepatitis B virus infection
      transmitted vertically and horizontally in the birth cohort during 1950-1985 in
      Japan.
AB  - AIM: We estimated numbers of persons, born between 1950 and 1985 in Japan, who
      were persistently infected with hepatitis B virus (HBV) through vertical and
      horizontal infections. METHODS: HBV carrier rates with vertical and horizontal
      infections were computed using sex- and age-specific prevalence rates of
      hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg) by
      mathematical model. Probabilities of vertical HBV transmission in babies born to
      carrier mothers with and without HBeAg were presumed to be 90% and 10%,
      respectively. RESULTS: HBV carrier rates with vertical infection stayed contrast
      at approximately 0.3% in birth cohorts through 36 years (1950-1985), both in men
      and women. By a remarkable constant, HBV carrier rates with horizontal infection
      decreased steadily from 1.43% to 0.10% in men and from 0.95% to 0.03% in women.
      The estimated total number of HBV carriers born between 1950 and 1985 was 522 500
      (355 488-693 606). Of them, the numbers of HBV carriers with vertical and
      horizontal infections were 197 574 (149 505-288 709) and 324 926 (205 983-404
      896); they accounted for 37.81% and 62.19%, respectively, with a ratio of 1:1.64.
      The ratio between vertical and horizontal infections was 1:2.20 in men and 1:1.06
      in women. CONCLUSION: Vertical HBV infection had stayed constant until
      immunoprophylaxis of mother-to-baby transmission was implemented in 1986 in
      Japan. In contrast, horizontal HBV infection decreased over years. The decrease
      would be due to many factors, including improved socioeconomic environments,
      advanced medical maneuvers and equipment, and careful vaccination procedures.

PMID- 24308777
TI  - Neonatal bee venom exposure induces sensory modality-specific enhancement of
      nociceptive response in adult rats.
AB  - OBJECTIVE: Previous studies have shown that inflammatory pain at the neonatal
      stage can produce long-term structural and functional changes in nociceptive
      pathways, resulting in altered pain perception in adulthood. However, the exact
      pattern of altered nociceptive response and associated neurochemical changes in
      the spinal cord in this process is unclear. METHOD: In this study, we used an
      experimental paradigm in which each rat first received intraplantar bee venom
      (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was
      followed 2 months later by a second intraplantar bee venom injection in the same
      rats to examine the difference in nociceptive responses. RESULTS: We found that
      neonatal inflammatory pain induced by the first BV injection significantly
      reduced baseline paw withdrawal mechanical threshold, but not baseline paw
      withdrawal thermal latency, when rats were examined 2 months from the first BV
      injection. Neonatal inflammatory pain also exacerbated mechanical, but not
      thermal, hyperalgesia in response to the second BV injection in these same rats.
      Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF,
      TrkA receptor, BDNF, TrkB receptor, IL-1beta, and COX-2 expression following the
      second BV injection, especially with prior BV exposure on postnatal day 21 or 28.
      CONCLUSION: These results indicate that neonatal inflammation produces sensory
      modality-specific changes in nociceptive behavior and alters neurochemistry in
      the spinal cord of adult rats. These results also suggest that a prior history of
      inflammatory pain during the developmental period might have an impact on
      clinical pain in highly susceptible adult patients.

PMID- 24308778
TI  - Influence of radioactivity on surface charging and aggregation kinetics of
      particles in the atmosphere.
AB  - Radioactivity can influence surface interactions, but its effects on particle
      aggregation kinetics have not been included in transport modeling of radioactive
      particles. In this research, experimental and theoretical studies have been
      performed to investigate the influence of radioactivity on surface charging and
      aggregation kinetics of radioactive particles in the atmosphere. Radioactivity
      induced charging mechanisms have been investigated at the microscopic level, and
      heterogeneous surface potential caused by radioactivity is reported. The
      radioactivity-induced surface charging is highly influenced by several
      parameters, such as rate and type of radioactive decay. A population balance
      model, including interparticle forces, has been employed to study the effects of
      radioactivity on particle aggregation kinetics in air. It has been found that
      radioactivity can hinder aggregation of particles because of similar surface
      charging caused by the decay process. Experimental and theoretical studies
      provide useful insights into the understanding of transport characteristics of
      radioactive particles emitted from severe nuclear events, such as the recent
      accident of Fukushima or deliberate explosions of radiological devices. 

PMID- 24308779
TI  - Semiparametric Bayesian commensurate survival model for post-market medical
      device surveillance with non-exchangeable historical data.
AB  - Trial investigators often have a primary interest in the estimation of the
      survival curve in a population for which there exists acceptable historical
      information from which to borrow strength. However, borrowing strength from a
      historical trial that is non-exchangeable with the current trial can result in
      biased conclusions. In this article we propose a fully Bayesian semiparametric
      method for the purpose of attenuating bias and increasing efficiency when jointly
      modeling time-to-event data from two possibly non-exchangeable sources of
      information. We illustrate the mechanics of our methods by applying them to a
      pair of post-market surveillance datasets regarding adverse events in persons on
      dialysis that had either a bare metal or drug-eluting stent implanted during a
      cardiac revascularization surgery. We finish with a discussion of the advantages
      and limitations of this approach to evidence synthesis, as well as directions for
      future work in this area. The article's Supplementary Materials offer simulations
      to show our procedure's bias, mean squared error, and coverage probability
      properties in a variety of settings. 

PMID- 24308780
TI  - Therapy response correlates with ALDH activity in ALDH low-positive childhood
      acute lymphoblastic leukemias.
AB  - The malignant cells of childhood acute lymphoblastic leukemia (ALL) do not form a
      homogenous entity but a collection of differently maturated blasts. The most
      immature leukemia cells may be more resistant to therapy than the bulk of more
      differentiated blasts. We studied 42 patients with childhood ALL treated
      according to the ALL-BFM 2000 protocol. At diagnosis, we determined the
      immunophenotype and the aldehyde dehydrogenase (ALDH) activity of the leukemic
      cells. Additionally, we investigated the expression of CD34, CD38 and CD45 to
      define a population of immunophenotypically immature cells (CD34(+)/CD38(-)/CD45(
      /low)). We then studied levels of minimal residual disease (MRD) after induction
      therapy (day 33) to determine therapy response. Including all cases (n = 42),
      there was no correlation between ALDH positive cells, CD34(+)/CD38(-)/CD45(-/low)
      cells and MRD levels. A subset of 18 ALLs displayed a more mature phenotype with
      low-ALDH positivity (< 1%). Analyzing this cohort, ALDH positive blasts
      overlapped with the CD34(+)/CD38(-)/CD45(-/low) population. The initial rate of
      ALDH positivity correlated with MRD levels at day 33 of therapy (r = 0.61, P <
      .01). We conclude that in pediatric ALL, ALDH positivity as a marker of
      immaturity and stemness has prognostic significance only in phenotypically mature
      cases when the ALDH activity is not a property of the majority of the leukemic
      blasts. In case of an immature ALL phenotype, ALDH activity might be an inherent
      characteristic of the whole leukemia and is not limited to a more immature
      subpopulation that could confer to resistance and increased MRD-levels during
      therapy. 

PMID- 24308781
TI  - Standard operating procedure changed pre-hospital critical care
      anaesthesiologists' behaviour: a quality control study.
AB  - INTRODUCTION: The ability of standard operating procedures to improve pre
      hospital critical care by changing pre-hospital physician behaviour is uncertain.
      We report data from a prospective quality control study of the effect on pre
      hospital critical care anaesthesiologists' behaviour of implementing a standard
      operating procedure for pre-hospital controlled ventilation. MATERIALS AND
      METHODS: Anaesthesiologists from eight pre-hospital critical care teams in the
      Central Denmark Region prospectively registered pre-hospital advanced airway
      management data according to the Utstein-style template. We collected pre
      intervention data from February 1st 2011 to January 31st 2012, implemented the
      standard operating procedure on February 1st 2012 and collected post intervention
      data from February 1st 2012 until October 31st 2012. We included transported
      patients of all ages in need of controlled ventilation treated with pre-hospital
      endotracheal intubation or the insertion of a supraglottic airways device. The
      objective was to evaluate whether the development and implementation of a
      standard operating procedure for controlled ventilation during transport could
      change pre-hospital critical care anaesthesiologists' behaviour and thereby
      increase the use of automated ventilators in these patients. RESULTS: The
      implementation of a standard operating procedure increased the overall prevalence
      of automated ventilator use in transported patients in need of controlled
      ventilation from 0.40 (0.34-0.47) to 0.74 (0.69-0.80) with a prevalence ratio of
      1.85 (1.57-2.19) (p = 0.00). The prevalence of automated ventilator use in
      transported traumatic brain injury patients in need of controlled ventilation
      increased from 0.44 (0.26-0.62) to 0.85 (0.62-0.97) with a prevalence ratio of
      1.94 (1.26-3.0) (p = 0.0039). The prevalence of automated ventilator use in
      patients transported after return of spontaneous circulation following pre
      hospital cardiac arrest increased from 0.39 (0.26-0.48) to 0.69 (0.58-0.78) with
      a prevalence ratio of 1.79 (1.36-2.35) (p = 0.00). CONCLUSION: We have shown that
      the implementation of a standard operating procedure for pre-hospital controlled
      ventilation can significantly change pre-hospital critical care
      anaesthesiologists' behaviour.

PMID- 24308782
TI  - Efficient synthesis of alpha-quaternary alpha-hydroxy-beta-amino esters via silyl
      glyoxylate-mediated three-component reactions.
AB  - An efficient method has been developed for the enantioselective synthesis of
      fully protected alpha-quaternary alpha-hydroxy-beta-amino esters via the coupling
      of three components: aryl Grignard reagents (or methyllithium), silyl glyoxylate,
      and N-tert-butanesulfinyl imines. This protocol enables successive formation of
      two C-C bonds and two adjacent chiral carbons with high stereocontrol in a one
      pot operation. 

PMID- 24308783
TI  - The role of ventral and preventral organs as attachment sites for segmental limb
      muscles in Onychophora.
AB  - BACKGROUND: The so-called ventral organs are amongst the most enigmatic
      structures in Onychophora (velvet worms). They were described as segmental,
      ectodermal thickenings in the onychophoran embryo, but the same term has also
      been applied to mid-ventral, cuticular structures in adults, although the
      relationship between the embryonic and adult ventral organs is controversial. In
      the embryo, these structures have been regarded as anlagen of segmental ganglia,
      but recent studies suggest that they are not associated with neural development.
      Hence, their function remains obscure. Moreover, their relationship to the
      anteriorly located preventral organs, described from several onychophoran
      species, is also unclear. To clarify these issues, we studied the anatomy and
      development of the ventral and preventral organs in several species of
      Onychophora. RESULTS: Our anatomical data, based on histology, and light,
      confocal and scanning electron microscopy in five species of Peripatidae and
      three species of Peripatopsidae, revealed that the ventral and preventral organs
      are present in all species studied. These structures are covered externally with
      cuticle that forms an internal, longitudinal, apodeme-like ridge. Moreover,
      phalloidin-rhodamine labelling for f-actin revealed that the anterior and
      posterior limb depressor muscles in each trunk and the slime papilla segment
      attach to the preventral and ventral organs, respectively. During embryonic
      development, the ventral and preventral organs arise as large segmental, paired
      ectodermal thickenings that decrease in size and are subdivided into the smaller,
      anterior anlagen of the preventral organs and the larger, posterior anlagen of
      the ventral organs, both of which persist as paired, medially-fused structures in
      adults. Our expression data of the genes Delta and Notch from embryos of
      Euperipatoides rowelli revealed that these genes are expressed in two, paired
      domains in each body segment, corresponding in number, position and size with the
      anlagen of the ventral and preventral organs. CONCLUSIONS: Our findings suggest
      that the ventral and preventral organs are a common feature of onychophorans that
      serve as attachment sites for segmental limb depressor muscles. The origin of
      these structures can be traced back in the embryo as latero-ventral segmental,
      ectodermal thickenings, previously suggested to be associated with the
      development of the nervous system.

PMID- 24308784
TI  - Safety profile of recombinant adeno-associated viral vectors: focus on alipogene
      tiparvovec (Glybera(r)).
AB  - There has been great interest over the past two decades in developing gene
      therapies (GTs) to treat a variety of diseases; however, translating research
      findings into clinical treatments have proved to be a challenge. A major
      milestone in the development of GT has been achieved with the approval of
      alipogene tiparvovec (Glybera((r))) in Europe for the treatment of familial
      lipoprotein lipase deficiency. At this important stage with the evolution of GT
      into the clinic, this review will examine the safety aspects GT with adeno
      associated virus (AAV) vectors. The topics that will be covered include acute
      reactions, immunological reactions to the AAV capsid and expressed transgene,
      viral biodistribution and shedding, DNA integration and carcinogenicity. These
      safety aspects of GT will be discussed with a focus on alipogene tiparvovec, in
      addition to other AAV vector GT products currently in clinical development.

PMID- 24308785
TI  - Therapeutic options in pulmonary hepatic vascular diseases.
AB  - Pulmonary-hepatic vascular disorders are frequent complications in patients with
      portal hypertension and cirrhosis. Both hepatopulmonary syndrome (HPS) and
      portopulmonary hypertension (POPH) are associated with increased morbidity and
      mortality. The diagnosis of HPS should be confirmed early by arterial blood gas
      analysis and contrast enhanced echocardiography whereas POPH is finally diagnosed
      by presence of pulmonary arterial hypertension evaluated via right heart
      catheterization and presence of portal hypertension. Therapeutic options are
      initiation of long term oxygen therapy and liver transplantation in patients with
      severe HPS. Patients with POPH should receive targeted medical therapies with
      endothelin receptor antagonists, phosphodiesterase-5 inhibitors and/or
      prostanoids. In contrast, beta-blockers should be avoided. It is unclear whether
      liver transplantation cures POPH or not. This review summarizes current knowledge
      of underlying conditions and focuses on therapeutic options in patients with
      pulmonary-hepatic vascular disorders. 

PMID- 24308786
TI  - Canagliflozin versus glimepiride treatment in patients with type 2 diabetes
      inadequately controlled with metformin (CANTATA-SU trial).
AB  - Evaluation of: Cefalu WT, Leiter LA, Yoon KH et al. Efficacy and safety of
      canagliflozin versus glimepiride in patients with Type 2 diabetes inadequately
      controlled with metformin (CANTATA-SU): 52-week results from a randomized, double
      blind, Phase III non-inferiority trial. Lancet 382, 941-950 (2013). The CANTATA
      SU study compared two doses of the sodium glucose cotransporter 2 inhibitor
      canagliflozin (CANA 100 and 300 mg) with the sulfonylurea, glimepiride (6-8 mg)
      in Type 2 diabetes mellitus patients inadequately controlled on metformin, over
      52 weeks. Glimepiride reduced the mean baseline HbA1C from 7.8-6.99%. CANA 100 mg
      reduced the baseline HbA1C from 7.8-6.98% and CANA 300 mg reduced HbA1C from 7.8
      6.87%. Fasting plasma glucose was lowered to a greater extent following CANA 100
      mg (1.3 mmol/l) and CANA 300 mg (1.52 mmol/l) as compared to glimepiride (1.02
      mmol/l). CANA 100 and 300 mg reduced body weight by 3.7 and 4.0 kg, respectively
      compared to a 0.7 kg increase with glimepiride. Blood pressure was modestly
      reduced by both CANA treatments. Both high-density lipoprotein and low-density
      lipoprotein cholesterol were increased by both doses of CANA compared to
      glimepiride. Documented hypoglycemia was lower with CANA, but polyuria,
      pollakiuria, genital mycotic and urinary tract infections were significantly
      greater in both doses of CANA compared to glimepiride.

PMID- 24308787
TI  - Non-benzodiazepine hypnotics and older adults: what are we learning about
      zolpidem?
AB  - Zolpidem and other non-benzodiazepine (BZD) hypnotic agents have become preferred
      drugs to manage insomnia. They are widely used among older adults because of
      perceived improved safety profiles compared with traditional BZDs. Accumulating
      data in recent years in patients over the age of 65, however, shed light on
      possible safety concerns of these medications and zolpidem specifically. Recent
      information regarding potential for excessive blood concentrations, effects on
      balance and memory and fracture risk data briefly is described. Clinicians should
      be aware of these most recent data. Non-drug therapies, as recommended in
      clinical guidelines, should be fully utilized for managing insomnia. Until better
      studies or pharmacovigilance data become available to guide patient selection for
      prescribing zolpidem and other non-BZDs, judicious use of these hypnotic agents
      in older adults is warranted. 

PMID- 24308788
TI  - Weight change, genetics and antiepileptic drugs.
AB  - Weight gain caused by antiepileptic drugs (AEDs) constitutes a serious problem in
      the management of people with epilepsy. AEDs associated with weight gain include
      sodium valproate, pregabalin and vigabatrin. Excessive weight gain can lead to
      non-compliance with treatment and to an exacerbation of obesity-related
      conditions. The mechanisms by which AEDs cause weight gain are not fully
      understood. It is likely that weight change induced by some AEDs has a genetic
      underpinning, and recent developments in DNA sequencing technology should speed
      the understanding, prediction and thus prevention of serious weight change
      associated with AEDs. This review focuses on the biology of obesity in the
      context of AEDs. Future directions in the investigations of the mechanism of
      weight change associated with these drugs and the use of such knowledge in
      tailoring the treatment of specific patient groups are explored. 

PMID- 24308789
TI  - Pediatric formulation issues identified in Paediatric Investigation Plans.
AB  - Since the European Paediatric Regulation was introduced in 2007, companies
      developing new medicinal products or new indications/routes of
      administration/pharmaceutical forms are obliged to present age-appropriate
      formulations for the pediatric population within a Paediatric Investigation Plan
      (PIP) to the European Medicines Agency. Our review highlights a number of
      discrepancies between what is proposed by applicants and what is considered
      acceptable by regulators, taking a sample of PIP applications assessed by a
      specialized Formulation Working Group (FWG) of the Paediatric Committee in 2009.
      This Working Group assessed 43% of the total number of validated PIP applications
      during that year. Ninety-two percent of the formulations assessed raised at least
      one issue, mainly relating to excipients, appropriateness of the route of
      administration or pharmaceutical form, dosing accuracy and patient's
      acceptability. A stronger focus on all these aspects, considering the targeted
      age range, the severity of the disease and the treatment duration, could
      streamline the development process. 

PMID- 24308790
TI  - Statin intolerance: more questions than answers.
AB  - The dramatic effectiveness of statins in improving the course of atherosclerotic
      cardiovascular disease tends to overshadow questions of statin intolerance. Thus
      after more than 25 years of clinical statin use, intolerance remains a poorly
      understood, frustrating issue for patients and providers. It has been
      extraordinarily difficult to define statin intolerance and its implications for
      clinical practice. Here, we briefly summarize current knowledge and raise
      questions that need to be addressed. 

PMID- 24308791
TI  - Novel tyrosine kinase inhibitors for renal cell carcinoma.
AB  - Although targeted therapy against VEGF and mTOR have revolutionized the treatment
      of advanced renal cell carcinoma (RCC), additional agents are required due to
      toxicity and resistance to currently available drugs. Some next-generation
      tyrosine kinase inhibitors have focused on VEGF, narrowing the spectrum of
      receptors which are inhibited and enhancing binding affinity. However, targeting
      novel receptors with tyrosine kinase inhibition of additional receptor targets
      has also emerged as an important future therapeutic strategy for RCC, both clear
      cell and variant histology. New pathways being targeted include FGF, angiopoietin
      and MET. In this review, we highlight five novel tyrosine kinase inhibitors in
      development for RCC: tivozanib; dovitinib; regorafenib; cabozantinib; and
      tivantinib. 

PMID- 24308792
TI  - Daclizumab, an IL-2 modulating antibody for treatment of multiple sclerosis.
AB  - Daclizumab is a monoclonal antibody specific for the IL-2R alpha chain (CD25).
      Daclizumab has been observed to have multiple mechanisms of action, which may
      contribute to beneficial effects in immune-related disease and particularly in
      relapsing and remitting multiple sclerosis (RRMS). These include inhibition of
      activated immune cells, increase of regulatory natural killer cells, effects on
      dendritic cells, inhibition of innate lymphoid tissue inducer cells and altered
      responses involving IL-2 transpresentation. The antibody has shown considerable
      promise in open-label and early Phase II clinical trials when used as a
      monotherapy, or in combination with IFN-beta. In recently completed randomized
      trials in RRMS, treatment with daclizumab monotherapy compared with placebo
      resulted in clinically meaningful and statistically significant reductions in
      relapses, active lesions on brain MRI and slowing of disability progression. A
      large Phase III trial in RRMS is ongoing. 

PMID- 24308793
TI  - Parent-child drug communication: pathway from parents' ad exposure to youth's
      marijuana use intention.
AB  - The authors combined the 2-step flow of communication model and the theory of
      planned behavior to create a framework to evaluate the effectiveness of a set of
      advertisements from the National Youth Anti-Drug Media Campaign promoting parent
      child drug communication. The sample consisted of 1,349 pairs of parents and
      children who responded to the first and second annual rounds of the National
      Survey of Parents and Youth, and 1,276 pairs from Rounds 3 and 4. Parents'
      exposure to the campaign reported at Round 1 was indirectly associated with
      youth's lowered intentions to use marijuana at Round 2. Ad exposure was
      associated with positive changes in parental attitudes toward drug communication
      and perceived social approval of antidrug communications. These two beliefs,
      along with perceived behavioral control, predicted parents' intentions to discuss
      drugs with their children. Parental intentions to discuss drugs reported at Round
      1 were associated with youth's report of actual drug communication with their
      parents at Round 2. Frequency and breadth of the topics in parent-child drug
      communication were associated with less positive attitudes toward marijuana use
      among youth who spoke with their parents. Together, the child's attitudes toward
      marijuana use and perceived ability to refuse marijuana use predicted youth's
      intentions to use marijuana. The proposed model fit well with the data and was
      replicated in a parallel analysis of the data from Rounds 3 and 4. Implications
      for future antidrug media campaign efforts are discussed. 

PMID- 24308794
TI  - Behavioral improvement of dementia residents in a group home with an increased
      number of residents after the Great East Japan Earthquake 2011.

PMID- 24308796
TI  - Seed-mediated synthesis of silver nanocrystals with controlled sizes and shapes
      in droplet microreactors separated by air.
AB  - Silver nanocrystals with uniform sizes were synthesized in droplet microreactors
      through seed-mediated growth. The key to the success of this synthesis is the use
      of air as a carrier phase to generate the droplets. The air not only separates
      the reaction solution into droplets but also provides O2 for the generation of
      reducing agent (glycolaldehyde). It also serves as a buffer space for the
      diffusion of NO, which is formed in situ due to the oxidative etching of Ag
      nanocrystals with twin defects. For the first time, we were able to generate Ag
      nanocrystals with controlled sizes and shapes in continuous production by using
      droplet microreactors. For Ag nanocubes, their edge lengths could be readily
      controlled in the range of 30-100 nm by varying the reaction time, the amount of
      seeds, and the concentration of AgNO3 in the droplets. Furthermore, we
      demonstrated the synthesis of Ag octahedra in the droplet microreactors. We
      believe that the air-driven droplet generation device can be extended to other
      noble metals for the production of nanocrystals with controlled sizes and shapes.

PMID- 24308795
TI  - Underlying mechanisms involved in the decrease of milk secretion during
      Escherichia coli endotoxin induced mastitis in lactating mice.
AB  - Mastitis, the inflammation of mammary glands resulting from bacterial infection,
      disrupts milk production in lactating mammary glands. In this study, we injected
      lipopolysaccharide (LPS), one of the endotoxins from Escherichia coli into mouse
      mammary glands to disrupt milk production, and we investigated the influence of
      LPS on nutrient uptake, synthesis, and secretion processes for milk component
      production in alveolar epithelial cells (AEC). The expression of genes relevant
      to the three-staged milk component production process (nutrient uptake,
      synthesis, and secretion of milk components) were down-regulated within 12 h
      after LPS injection in AEC. The internalization of glucose transporter 1 (GLUT-1)
      from the basolateral membrane to the cytoplasm occurred in accordance with the
      down-regulation of gene expression 3 h after LPS injection. The abnormal
      localization of adipophilin and beta-casein was also observed in the LPS-injected
      mammary glands. SLC7A1, an amino acid transporter, was up-regulated 3 and 6 h
      after LPS injection. Furthermore, the inactivation of signal transducer and
      activator of transcription 5 (STAT5) and the activation of STAT3 and nuclear
      factor-kappa B (NFkappaB) occurred 3 h after LPS injection. These results
      indicate that the nutrient uptake, synthesis, and secretion of milk components in
      AEC are rapidly shut down in the lactating mammary glands after LPS injection.

PMID- 24308797
TI  - Systematic review with meta-analysis: highly selective 5-HT4 agonists
      (prucalopride, velusetrag or naronapride) in chronic constipation.
AB  - BACKGROUND: Highly selective 5-HT4 agonists have been suggested for the treatment
      of chronic constipation (CC). AIM: To assess the effects of highly selective 5
      HT4 agonists (prucalopride, velusetrag or naronapride) on patient-important
      clinical efficacy outcomes and safety in adults with CC. METHODS: We searched the
      medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane
      Library, and Web of Science/Scopus for randomised, controlled trials of highly
      selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy
      (maximum 12 weeks) or date limitations. Data were extracted from intention-to
      treat analyses, pooled using a random-effects model, and reported as relative
      risk (RR), mean differences, or standardised mean differences with 95% confidence
      intervals (CI). RESULTS: Main outcomes included stool frequency, Patient
      Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM)
      and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1
      velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5
      HT4 agonists was superior for all outcomes: mean >=3 spontaneous complete bowel
      movements (SCBM)/week (RR = 1.85; 95% CI 1.23-2.79); mean >=1 SCBM over baseline
      (RR = 1.57; 95% CI 1.19, 2.06); >=1 point improvement in PAC-QOL and PAC-SYM
      scores. The only active comparator trial of prucalopride and PEG3350 suggested
      PEG3350 is more efficacious for some end points. Adverse events were more common
      with highly selective 5-HT4 agonists, but were generally minor; headache was the
      most frequent. Most trials studied prucalopride. CONCLUSION: Demonstration of
      efficacy on patient-important outcomes and a favourable safety profile support
      the continued use and development of highly selective 5-HT4 agonists in the
      treatment of chronic constipation.

PMID- 24308798
TI  - Children's parasympathetic reactivity to specific emotions moderates response to
      intervention for early-onset aggression.
AB  - Following theories that individual differences in respiratory sinus arrhythmia
      (RSA) denote differential sensitivity to environmental influences, this study
      examines whether differences in RSA reactivity to specific emotional challenges
      predict differential response to intervention. We present data from a randomized
      clinical trial of a targeted intervention for early onset aggression. In
      collaboration with a high-risk urban school district, 207 kindergarten children
      (73% African American, 66% male), identified by their teachers as having high
      levels of aggressive and disruptive behavior, were recruited. All children
      received a universal social-emotional curriculum. One hundred children were
      randomly assigned to an additional intervention consisting of weekly peer-based
      social skills training. Complete RSA data were available for 139 of the children.
      Teacher-reported externalizing symptoms and emotion regulation in 1st grade (post
      intervention) were examined controlling for baseline levels. First-grade peer
      nominations of aggressive behavior, controlling for baseline nominations, were
      also examined as outcomes. No effect of resting RSA was found. However, greater
      reactivity to anger was associated with higher externalizing symptoms and lower
      emotion regulation skills in 1st grade relative to low reactive children. Lower
      reactivity to fear was associated with greater improvement over time, an effect
      that was enhanced in the targeted intervention condition. Results suggest that
      measures of affective reactivity may provide insight into children's capacity to
      benefit from different types of interventions. 

PMID- 24308799
TI  - Risks to patient safety associated with implementation of electronic applications
      for medication management in ambulatory care--a systematic review.
AB  - BACKGROUND: The objective was to find evidence to substantiate assertions that
      electronic applications for medication management in ambulatory care (electronic
      prescribing, clinical decision support (CDSS), electronic health record, and
      computer generated paper prescriptions), while intended to reduce prescribing
      errors, can themselves result in errors that might harm patients or increase
      risks to patient safety. METHODS: Because a scoping search for adverse events in
      randomized controlled trials (RCTs) yielded few relevant results, we
      systematically searched nine databases, including MEDLINE, EMBASE, and The
      Cochrane Database of Systematic Reviews for systematic reviews and studies of a
      wide variety of designs that reported on implementation of the interventions.
      Studies that had safety and adverse events as outcomes, monitored for them,
      reported anecdotally adverse events or other events that might indicate a threat
      to patient safety were included. RESULTS: We found no systematic reviews that
      examined adverse events or patient harm caused by organizational interventions.
      Of the 4056 titles and abstracts screened, 176 full-text articles were assessed
      for inclusion. Sixty-one studies with appropriate interventions, settings and
      participants but without patient safety, adverse event outcomes or monitoring for
      risks were excluded, along with 77 other non-eligible studies. Eighteen
      randomized controlled trials (RCTs), 5 non-randomized controlled trials (non
      R,CTs) and 15 observational studies were included. The most common electronic
      intervention studied was CDSS and the most frequent clinical area was cardio
      vascular, including anti-coagulants. No RCTS or non-R,CTS reported adverse event.
      Adverse events reported in observational studies occurred less frequently after
      implementation of CDSS. One RCT and one observational study reported an increase
      in problematic prescriptions with electronic prescribing CONCLUSIONS: The safety
      implications of electronic medication management in ambulatory care have not been
      established with results from studies included in this systematic review. Only a
      minority of studies that investigated these interventions included threats to
      patients' safety as outcomes or monitored for adverse events. It is therefore not
      surprising that we found little evidence to substantiate fears of new risks to
      patient safety with their implementation. More research is needed to focus on the
      draw-backs and negative outcomes that implementation of these interventions might
      introduce.

PMID- 24308800
TI  - Diversity of epothilone producers among Sorangium strains in producer-positive
      soil habitats.
AB  - Large-scale surveys show that the anti-tumour compounds known as epothilones are
      produced by only a small proportion of Sorangium strains, thereby greatly
      hampering the research and development of these valuable compounds. In this
      study, to investigate the niche diversity of epothilone-producing Sorangium
      strains, we re-surveyed four soil samples where epothilone producers were
      previously found. Compared with the < 2.5% positive strains collected from
      different places, epothilone producers comprised 25.0-75.0% of the Sorangium
      isolates in these four positive soil samples. These sympatric epothilone
      producers differed not only in their 16S rRNA gene sequences and morphologies but
      also in their production of epothilones and biosynthesis genes. A further
      exploration of 14 soil samples collected from a larger area around a positive
      site showed a similar high positive ratio of epothilone producers among the
      Sorangium isolates. The present results suggest that, in an area containing
      epothilone producers, the long-term genetic variations and refinements resulting
      from selective pressure form a large reservoir of epothilone-producing Sorangium
      strains with diverse genetic compositions.

PMID- 24308801
TI  - Cytotoxic response persists in subjects treated for tuberculosis decades ago.
AB  - BACKGROUND: Data exploring the potential use of effector molecules produced by
      cytotoxic T lymphocytes (CTLs) in the immunodiagnostics of tuberculosis (TB) are
      scarce. The present study focused a) to gain an insight into the discriminatory
      power of CTLs in patients with acute pulmonary or extra-pulmonary TB, or latent
      tuberculosis infection (LTBI); and b) to evaluate the influence of various anti
      TB therapeutic schemes on the immunological profiles of residual CTLs. METHODS:
      Immunological signatures of antigen-specific CTLs were explored in patients with
      active pulmonary and extra-pulmonary TB, LTBI and in those treated for TB decades
      ago by using ELISPOT, intracellular flow cytometry and extracellular CD107a
      detection. RESULTS: No difference was seen between active TB, LTBI or any of
      those treated for TB in the ELISPOT analysis of antigen-specific Granzyme B
      (GrB), Perforin (Prf) and interferon-gamma (IFN-gamma) producing lymphocytes, the
      FACS analysis of the intracellular expression of IFN-gamma, or the surface
      expression of CD107a degranulation factor of both CD8+ and CD4+ antigen-specific
      T cell subsets. The effector memory (TEM) phenotype proved predominant in the
      surface marker profiling both in active TB and LTBI. The proportion of the CD107a
      degranulation factor proved higher in the central memory (TCM) than in the other
      cell subsets in all the study groups. Interestingly, functionally and
      phenotypically similar CTLs profiles were observed in active TB, LTBI and in all
      the three groups treated for TB. CONCLUSION: The phenotypic and functional
      profiling of CTLs has a limited potential in the immunodiagnostics of active TB.
      Antigen-specific CTLs persist in patients treated for TB decades ago regardless
      of the efficacy of implemented and completed anti-TB therapy.

PMID- 24308802
TI  - Influence of cross sectional geometry on surface plasmon polariton propagation in
      gold nanowires.
AB  - We investigated the effects of cross sectional geometry on surface plasmon
      polariton propagation in gold nanowires (NWs) using bleach-imaged plasmon
      propagation and electromagnetic simulations. Chemically synthesized NWs have
      pentagonally twinned crystal structures, but recent advances in synthesis have
      made it possible to amplify this pentagonal shape to yield NWs with a five
      pointed-star cross section and sharp end tips. We found experimentally that NWs
      with a five-pointed-star cross section, referred to as SNWs, had a shorter
      propagation length for surface plasmon polaritons at 785 nm, but a higher
      effective incoupling efficiency compared to smooth NWs with a pentagonal cross
      section, labeled as PNWs. Electromagnetic simulations revealed that the electric
      fields were localized at the sharp ridges of the SNWs, leading to higher
      absorptive losses and hence shorter propagation lengths compared to PNWs. On the
      other hand, scattering losses were found to be relatively uncorrelated with cross
      sectional geometry, but were strongly dependent on the plasmon mode excited. Our
      results provide insight into the shape-dependent waveguiding properties of
      chemically synthesized metal NWs and the mode-dependent loss mechanisms that
      govern surface plasmon polariton propagation. 

PMID- 24308803
TI  - The genetic ablation or pharmacological inhibition of TRPV1 signalling is
      beneficial for the restoration of quiescent osteoclast activity in ovariectomized
      mice.
AB  - BACKGROUND AND PURPOSE: Osteoporosis is a condition characterized by a decrease
      in bone density, which decreases its strength and results in fragile bones. The
      endocannabinoid/endovanilloid system has been shown to be involved in the
      regulation of skeletal remodelling. The aim of this study was to investigate the
      possible modulation of bone mass mediated by the transient receptor potential
      vanilloid type 1 channel (TRPV1) in vivo and in vitro. EXPERIMENTAL APPROACH: A
      multidisciplinary approach, including biomolecular, biochemical and morphological
      analysis, was used to investigate the involvement of TRPV1 in changes in bone
      density in vivo and osteoclast activity in vitro, in wild-type and Trpv1(-/-)
      mice, that had undergone ovariectomy or had a sham operation. KEY RESULTS:
      Genetic deletion of Trpv1 as well as pharmacological inhibition/desensitization
      of TRPV1 signalling dramatically reduced the osteoclast activity in vitro and
      prevented the ovariectomy-induced bone loss in vivo, whereas the expression of
      cannabinoid type 2 (CB2 ) receptors was increased. CONCLUSIONS AND IMPLICATIONS:
      These findings highlight the pivotal role TRPV1 channels play in bone resorption
      and suggest a possible cross-talk between TRPV1 and CB2 receptors. Based on these
      results, hybrid compounds acting on both TRPV1 and CB2 receptors in an opposite
      manner could provide a future pharmacological tool for the treatment of diseases
      associated with disturbances in the bone remodelling process.

PMID- 24308804
TI  - Tricyclic antidepressants: is your patient taking them? Observations on adherence
      and unreported use using prescriber-reported medication lists and urine drug
      testing.
AB  - OBJECTIVE: Tricyclic antidepressants (TCAs) are first-line treatment for
      neuropathic pain. Despite widespread use, many health care providers do not know
      which patients are currently taking TCAs. The objective of this retrospective
      data analysis was to determine adherence rates to amitriptyline, nortriptyline,
      or imipramine. The rate at which patients used TCAs (confirmed by presence of TCA
      in the urine) but did not inform their health care provider is also reported (non
      informed prescriber rate). Finally, the effects of age, sex, and number of
      prescriptions on adherence and non-informed prescriber rates were assessed.
      METHODS: Urinary excretion data were obtained from 55,296 patients with pain and
      were analyzed using liquid chromatography tandem mass spectrometry in a multiplex
      assay which included amitriptyline, nortriptyline, and imipramine. RESULTS: The
      adherence rate was 66% (1,407/2,137); the rate of non-informed prescribers was 3%
      (1,547/55,296) among the general population, and 52% (1,547/2,954) when only TCA
      users were considered. While adherence was higher among older and female
      subjects, the number of other medications did not affect adherence rate.
      CONCLUSIONS: This analysis reveals that many prescribers are not informed when
      patients start and stop using TCAs.

PMID- 24308805
TI  - An analysis of the levels of the soluble form of the endothelial protein C
      receptor in children with Henoch-Schonlein Purpura.
AB  - The pathogenesis of Henoch-Schonlein Purpura (HSP) has not been clearly defined.
      Inflammatory cytokines have been associated with HSP but there are only a few
      reports that have focused on coagulation. The endothelial protein C receptor
      (EPCR), which has anticoagulant and antiinflammatory activity, is the key
      component of the protein C pathway. Recent studies have implicated the soluble
      form of EPCR (sEPCR) in Wegener's granulomatosis, Behcet's disease, and systemic
      lupus erythematosus. The aim of this study was to evaluate the levels of sEPCR in
      HSP children. Twenty-two children with HSP and 17 healthy children were included.
      We found no significant differences (P > .05) between patient and control groups
      in the levels of von Willebrand factor and thrombomodulin. The median sEPCR
      values in the HSP group were lower than the control group (79 vs. 102 ng/mL,
      respectively) (P > .05). The mean sEPCR value in HSP patients with severe
      abdominal pain was lower than without (88.8 +/- 54.9 vs. 108.2 +/- 66.3 ng/mL,
      respectively) (P > .05). In addition, the mean IL-6 serum levels were
      significantly elevated in HSP patients during the acute stage of HSP (2.1 +/- 1.7
      vs. 1.5 +/- 1.2 pg/mL, P = .038). We also observed a slight negative correlation
      between the levels of sEPCR and IL-6 (R = -.135, P > .05). To our knowledge, this
      was the first study to analyze sEPCR levels in HSP. Our results did not
      conclusively identify a direct role of sEPCR in HSP, but our findings warrant
      further investigations, especially in severe HSP cases characterized by
      gastrointestinal bleeding or renal involvement.

PMID- 24308806
TI  - Optimizing engagement with Internet-based health behaviour change interventions:
      comparison of self-assessment with and without tailored feedback using a mixed
      methods approach.
AB  - OBJECTIVES: Internet-based health behaviour interventions have variable effects
      on health-related outcomes. Effectiveness may be improved by optimizing the
      design of interventions. This study examined the specific effect on engagement of
      providing two different design features - tailoring and self-assessment. DESIGN:
      Three versions of an Internet-delivered intervention to support the self-care of
      mild bowel problems were developed that provided (1) self-assessment without
      tailored feedback, (2) self-assessment with tailored feedback, and (3) generic
      information only. METHODS: A qualitative study explored participants' engagement
      with each version of the intervention (N = 24). A larger quantitative study
      systematically compared participants' use of the intervention and self-reported
      engagement using a partial factorial design (n = 178). RESULTS: Findings from the
      qualitative study suggested that self-assessment without tailored feedback
      appeared to be less acceptable to participants because it was viewed as offering
      no personal benefit in the absence of personalized advice. In the quantitative
      study, self-assessment without tailored feedback was associated with greater
      dropout than when provided in conjunction with tailored feedback. There were
      significant group differences in participants' engagement with the intervention
      and perceptions of the intervention. Self-assessment without tailored feedback
      was rated as marginally less engaging and was associated with fewer positive
      perceptions than the generic information condition. CONCLUSIONS: The
      acceptability of self-assessment or monitoring components may be optimized by
      also providing tailored feedback. Without tailored feedback, these components do
      not appear to be any more engaging than generic information provision. Statement
      of contribution What is already known on this subject? Digital interventions can
      be effective for improving a range of health outcomes and behaviours. There is
      huge variation in the success of different interventions using different
      combinations of design features. What does this study add? This study used a
      systematic experimental design to identify the effect on engagement of providing
      interactive intervention design features alone and in combination. Intervention
      engagement was better when self-assessment was provided in conjunction with
      tailored feedback.

PMID- 24308807
TI  - Boiling of simulated tap water: effect on polar brominated disinfection
      byproducts, halogen speciation, and cytotoxicity.
AB  - Tap water typically contains numerous halogenated disinfection byproducts (DBPs)
      as a result of disinfection, especially of chlorination. Among halogenated DBPs,
      brominated ones are generally significantly more toxic than their chlorinated
      analogues. In this study, with the aid of ultra performance liquid
      chromatography/electrospray ionization-triple quadrupole mass spectrometry by
      setting precursor ion scans of m/z 79/81, whole spectra of polar brominated DBPs
      in simulated tap water samples without and with boiling were revealed. Most polar
      brominated DBPs were thermally unstable and their levels were substantially
      reduced after boiling via decarboxylation or hydrolysis; the levels of a few
      aromatic brominated DBPs increased after boiling through decarboxylation of their
      precursors. A novel adsorption unit for volatile total organic halogen was
      designed, which enabled the evaluation of halogen speciation and mass balances in
      the simulated tap water samples during boiling. After boiling for 5 min, the
      overall level of brominated DBPs was reduced by 62.8%, of which 39.8% was
      volatilized and 23.0% was converted to bromide; the overall level of chlorinated
      DBPs was reduced by 61.1%, of which 44.4% was volatilized and 16.7% was converted
      to chloride; the overall level of halogenated DBPs was reduced by 62.3%. The
      simulated tap water sample without boiling was cytotoxic in a chronic (72 h)
      exposure to mammalian cells; this cytotoxicity was reduced by 76.9% after boiling
      for 5 min. The reduction in cytotoxicity corresponded with the reduction in
      overall halogenated DBPs. Thus, boiling of tap water can be regarded as a
      "detoxification" process and may reduce human exposure to halogenated DBPs
      through tap water ingestion. 

PMID- 24308808
TI  - Trigeminocardiac reflex: current trends.
AB  - Since the first introduction of the trigeminocardiac reflex (TCR) in 1999,
      substantial new knowledge about this brainstem reflex has been created. First, by
      different clinical case reports and case studies, and second, from basic research
      that gives inputs from bench to bedside. In the present work, the authors
      therefore introduce the molecular/anatomical knowledge of the TCR and show its
      different connections to clinical aspects. Special reference is given to
      prevention and treatment of the TCR; but always with a link to knowledge of the
      basis sciences. In such a context different topics of future interest are
      introduced. 

PMID- 24308810
TI  - Independent prognostic value of MRI beyond existing methods of determining
      cardiovascular risk - is there a role?
AB  - Imaging is a highly attractive option for improved risk stratification, as it
      allows direct detection and quantification of subclinical and clinical disease
      burden. Among available imaging techniques, MRI may be particularly suited for
      comprehensive cardiovascular risk assessment given its non-ionizing nature and
      high soft-tissue contrast. In this editorial, the authors review the emerging
      evidence in different clinical scenarios, indicating the incremental role of MRI
      for determining risk for future cardiovascular events. 

PMID- 24308809
TI  - See the light: can optogenetics restore healthy heartbeats? And, if it can, is it
      really worth the effort?
AB  - Cardiac optogenetics is an exciting new methodology in which light-sensitive ion
      channels are expressed in heart tissue to enable optical control of
      bioelectricity. This technology has the potential to open new avenues for safely
      and effectively treating rhythm disorders in the heart with gentle beams of
      light. Recently, we developed a comprehensive framework for modeling cardiac
      optogenetics. Simulations conducted in this platform will provide insights to
      guide in vitro investigation and steer the development of therapeutic
      applications - these are the first steps toward clinical translation. In this
      editorial, we review literature relevant to light-sensitive protein delivery and
      intracardiac illumination to provide a holistic feasibility assessment for
      optogenetics-based arrhythmia termination therapy. We then draw on examples from
      computational work to show that the optical control paradigm has undeniable
      advantages that cannot be attained with conventional electrotherapy. Hence, we
      argue that cardiac optogenetics is more than a flashy substitute for current
      approaches. 

PMID- 24308811
TI  - Intramolecular Fischer indole synthesis in combination with alkyne
      hydroarylation: synthesis of tetracyclic chromeno-indoles.
AB  - Aryl hydrazides bearing a carbonyl function connected through an alkyne tether
      underwent an intramolecular Fischer indolization and alkyne hydroarylation in a
      tandem fashion to afford novel tetracyclic chromeno-indoles. The accompanying
      isomerization of the 2H-chromene double bond can be avoided by stopping the
      tandem process at the indolophane stage and conducting the alkyne-hydroarylation
      reaction separately in the absence of a proton source. 

PMID- 24308812
TI  - Prevalence of active hepatitis C virus infections among general public of Lahore,
      Pakistan.
AB  - BACKGROUND: To find out the prevalence of active hepatitis C virus (HCV)
      infections among general public in Lahore city, since data concerning the
      prevalence of active HCV in this city is currently unavailable. METHODS: Blood
      samples were collected randomly from individuals visiting different clinical
      laboratories in Lahore. Serum was separated and processed by nested PCR
      qualitative assay for the detection of HCV RNA. The samples were categorized into
      different age groups on the basis of pre-test questionnaires in order to record
      the age-wise differences regarding the prevalence of active HCV. Data were
      analyzed statistically using Chi-Square test. RESULTS: Out of the 4246 blood
      samples analyzed in this study, 210 were confirmed to be positive for active HCV
      infection. Gender-wise active HCV prevalence revealed no significant difference
      [OR = 1.10 CI = (0.83-1.46), p > 0.05]. However, among the age groups the highest
      prevalence was observed in the age groups 20-29 (7.7%) and 30-39 years (6.4%)
      with odds of prevalence of 14.8% (OR = 2.48, CI = (1.40-4.38), p < 0.05) and
      10.3% (OR = 2.03, CI = (1.10-3.71), respectively. In age groups above 40 years
      (40-49, 50-59 and >59 years), a decrease in levels of active HCV prevalence was
      observed. CONCLUSIONS: Among tested samples, 4.9% of the subjects were confirmed
      to harbour active HCV infections and the "middle aged" population in Lahore was
      found to be at a higher risk of the HCV ailments compared to both their younger
      and older peers.

PMID- 24308813
TI  - Does Metformin affect ER, PR, IGF-1R, beta-catenin and PAX-2 expression in women
      with diabetes mellitus and endometrial cancer?
AB  - OBJECTIVE: Diabetes mellitus, as a risk factor for endometrial cancer (EC),
      causes an increase in insulin and IGF-1 concentrations in the blood serum. The
      increase in insulin and IGF-1 are considered mitogenic factors contributory to
      cancer development. Studies suggest that metformin has preventive activity,
      decreasing mortality and the risk of neoplasms. Since estrogen (ER), progesterone
      (PR) and IGF-1 (IGF-1R) receptor expression and beta-catenin and PAX-2 mutations
      are significant in the development of endometrial cancer, it was decided to study
      these factors in patients with endometrial cancer and type 2 diabetes mellitus
      (DM2), and to establish the effects of metformin on their expression. METHODS:
      The expression of ER, PR, IGF-1R, beta-catenin and PAX-2 have been
      immunohistochemically investigated in 86 type I endometrial cancer specimens.
      Patients were grouped according to the presence of DM2 and the type of
      hypoglycemic treatment administered. RESULTS: Comparing EC patients with DM2 and
      normal glycemic status, we found increased IGF-1R expression in women with DM2. A
      decrease in ER expression was noted in women with EC and DM2 receiving metformin
      as compared to women treated with insulin (p = 0.004). There was no statistically
      significant difference in PR, IGF-1R, beta-catenin and PAX-2 expression among
      women receiving metformin and other hypoglycemic treatment. CONCLUSION: Although
      epidemiological studies suggest the beneficial role of metformin in many human
      cancers, there are still few studies confirming its favorable effect on
      endometrial cancer. Decreased ER expression in patients receiving metformin needs
      further research to allow evaluation of its clinical significance.

PMID- 24308814
TI  - Validation of a translated and culturally adapted Iranian version of the
      International Index of Erectile Function.
AB  - This study aimed to examine the psychometric values of a Farsi-translated version
      of the International Index of Erectile Function among a population sample of
      Iranian men. A community sample of 2,345 healthy men and a clinical sample of 421
      men with diagnosed erectile function from 2 cities of Iran participated in the
      study. Participants were asked to complete the International Index of Erectile
      Function, the Life Satisfaction questionnaire, and a demographic questionnaire at
      baseline. Four weeks later, both samples were asked to recomplete the
      International Index of Erectile Function. The response rates were 84% (n = 1,969)
      and 98% (n = 412) for healthy men and men with erectile function, respectively.
      The retest reliability of the International Index of Erectile Function showed
      excellent intraclass correlation coefficients for both the healthy and patient
      samples. The International Index of Erectile Function subscales correlated
      significantly with the scores resulting from the clinical rating of erectile
      function conducted by urologists. Men with erectile function, as diagnosed by
      urologists, had significant lower scores in all subscales. The results of the
      exploratory factor analysis indicated that the International Index of Erectile
      Function could be summarized into a 5-component solution.The Iranian version of
      the International Index of Erectile Function was found to be a highly valid and
      reliable instrument to be used for the assessment of erectile function in
      clinical and population samples. 

PMID- 24308816
TI  - Characteristics of functional bowel disorder patients: a cross-sectional survey
      using the Rome III criteria.
AB  - BACKGROUND: There is some evidence that, despite attempts to classify them
      separately, functional bowel disorders are not distinct entities and that such
      divisions are artificial. AIM: To examine this issue in a large cohort of
      secondary care patients. METHODS: Consecutive, unselected adults with
      gastrointestinal (GI) symptoms attending out-patient clinics at two hospitals in
      Hamilton, Ontario were recruited. Demographic data, symptoms and presence of
      anxiety, depression or somatisation were collected prospectively. We used
      validated questionnaires, including the Rome III questionnaire, with patients
      categorised as having irritable bowel syndrome (IBS), functional diarrhoea or
      chronic idiopathic constipation (CIC). We compared data between these disorders,
      and measured degree of overlap between them by suspending their mutual
      exclusivity. RESULTS: Of 3656 patients providing complete lower GI symptom data,
      1551 (42.4%) met criteria for a functional bowel disorder. Diarrhoea-predominant
      IBS (IBS-D) patients were younger, and more were female, met criteria for
      anxiety, and reported somatisation-type behaviour, compared with functional
      diarrhoea. Only loose, mushy or watery stools were more common in functional
      diarrhoea. When mutual exclusivity was suspended, overlap occurred in 27.6%.
      Constipation-predominant IBS (IBS-C) patients were younger, and more were female,
      had never married, reported anxiety type symptoms and exhibited somatisation-type
      behaviour. One in five CIC patients reported abdominal pain or discomfort. All
      constipation symptoms were more common in IBS-C. When the mutual exclusivity was
      suspended, overlap occurred in 18.1%. CONCLUSIONS: There were significant
      differences in demographics between individuals with functional bowel disorders.
      Despite this, the Rome III classification system falls short of describing unique
      entities.

PMID- 24308815
TI  - Genome-wide association studies and prediction of 17 traits related to phenology,
      biomass and cell wall composition in the energy grass Miscanthus sinensis.
AB  - * Increasing demands for food and energy require a step change in the
      effectiveness, speed and flexibility of crop breeding. Therefore, the aim of this
      study was to assess the potential of genome-wide association studies (GWASs) and
      genomic selection (i.e. phenotype prediction from a genome-wide set of markers)
      to guide fundamental plant science and to accelerate breeding in the energy grass
      Miscanthus. * We generated over 100,000 single-nucleotide variants (SNVs) by
      sequencing restriction site-associated DNA (RAD) tags in 138 Micanthus sinensis
      genotypes, and related SNVs to phenotypic data for 17 traits measured in a field
      trial. * Confounding by population structure and relatedness was severe in naive
      GWAS analyses, but mixed-linear models robustly controlled for these effects and
      allowed us to detect multiple associations that reached genome-wide significance.
      Genome-wide prediction accuracies tended to be moderate to high (average of
      0.57), but varied dramatically across traits. As expected, predictive abilities
      increased linearly with the size of the mapping population, but reached a plateau
      when the number of markers used for prediction exceeded 10,000-20,000, and tended
      to decline, but remain significant, when cross-validations were performed across
      subpopulations. * Our results suggest that the immediate implementation of
      genomic selection in Miscanthus breeding programs may be feasible.

PMID- 24308817
TI  - Individual cognitive behavioural therapy for psychosis (CBTp): a systematic
      review of qualitative literature.
AB  - BACKGROUND: Individual Cognitive Behaviour Therapy for psychosis (CBTp) is the
      first line recommended psychological intervention for adults diagnosed with
      schizophrenia. However, little is yet known about service users' subjective
      experiences of CBTp. AIMS: This study aimed to conduct a systematic review of
      qualitative literature to examine service user perspective of CBTp. METHOD: A
      thematic synthesis of qualitative studies examining service users' experiences of
      CBTp was conducted. A total of six studies were included in the analysis.
      RESULTS: Three superordinate themes were identified: therapeutic alliance;
      facilitating change; and challenges of applying CBTp. CONCLUSION: Overall, CBTp
      is a helpful and acceptable therapeutic approach to service users. Developing a
      collaborative therapeutic relationship is essential. The applications of CBTp can
      be problematic and the therapist and client need to work together to overcome
      these difficulties.

PMID- 24308818
TI  - Structural basis for the inhibition of human lysozyme by PliC from Brucella
      abortus.
AB  - Lysozymes are the first line of defense for a diverse range of organisms that
      catalyze the degradation of bacterial peptidoglycan. Gram-negative bacteria
      produce proteinaceous lysozyme inhibitors to protect themselves from the action
      of lysozymes. To date, MliC or PliC (membrane-bound or periplasmic inhibitor of c
      type lysozyme, respectively) has been found in various Gram-negative bacteria.
      Here, we report the crystal structures of Brucella abortus PliC and its complex
      with human c-type lysozyme. The complex structure demonstrates that the invariant
      loop of MliC/PliC plays a crucial role in the inhibition of lysozyme via its
      insertion into the active site cleft of the lysozyme, as previously observed in
      the complex structure of Pseudomonas aeruginosa MliC and chicken c-type lysozyme.
      We identified a new binding interface between a loop adjacent to the active site
      of human lysozyme and a loop carrying Glu112 of B. abortus PliC, the structure of
      which was disordered in P. aeruginosa MliC. Because MliC/PliC family members have
      been implicated as putative colonization or virulence factors, the structures and
      mechanism of action of MliC/PliC will be relevant to the control of bacterial
      growth in animal hosts. 

PMID- 24308819
TI  - PCR-based allelic discrimination for glucose-6-phosphate dehydrogenase (G6PD)
      deficiency in Ugandan umbilical cord blood.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked
      disorder in the world. G6PD deficiency puts children at risk for
      hyperbilirubinemia and kernicterus during the newborn period and an increased
      risk of severe hemolysis after exposure to many antimalarial medications. A
      laboratory diagnosis of G6PD deficiency is rare in the developing world due to
      limited resources. We developed a TaqMan-based allele-specific assay to rapidly
      determine rates of G6PD deficiency contributing alleles (G202A and A376G) in East
      Africa. We tested umbilical cord blood from 100 Ugandan newborns and found that
      the overall allele frequency of G202A was .13 and A376G was .32. The overall
      incidence of G6PD A- (G202A/A376G) was 6%; all A- variants were males. There was
      no correlation between G6PD deficiency and umbilical cord blood hemoglobin, white
      blood count, platelet count, or other hematologic parameters. Allele-specific PCR
      can serve as a rapid method to determine specific G6PD deficiency allele
      frequencies in a given population and as a diagnostic tool in a hospital setting
      in which laboratory resources are present. 

PMID- 24308820
TI  - Detritus-based assemblage responses under salinity stress conditions in a disused
      aquatic artificial ecosystem.
AB  - BACKGROUND: Despite the plethora of approaches, the sensitivity of the methods to
      measure the relationship between the abundance and biomass curves in stressed
      detritus-based ecosystems still remain to be refined. In this work, we report the
      comparison between biomass and abundance in a set of detritus-based
      macrozoobenthic assemblages located in six sampling pools with different salinity
      in an artificial aquatic ecosystem (disused Tarquinia Saltworks), using two
      diversity/dominance approaches (Abundance/Biomass Comparisons, or ABC, and
      Whittaker plots). We also evaluated the contribution of abundances and biomasses
      diversity (Simpson index) and nestedness, which measures the order by which
      macroinvertebrates colonized the detrital resource. RESULTS: The outputs obtained
      by both ABC curves and Whittaker plots highlight two different thresholds in
      assemblage structure: between about 44 and 50 practical salinity unit (psu) and
      between 50 and 87 psu, respectively. The first threshold was due to a turnover in
      taxon composition between assemblages, the second threshold (evidenced by
      Whittaker plots) was due to a change in taxon richness (lower in pools with
      higher salinity: i.e. > 50 psu). Moreover, a normal-shaped pattern in diversity
      (Simpson index) emerged, suggestive of an intermediate disturbance effect. The
      nested pattern did not show significant differences when considering the density
      and biomass of the sampled taxa, providing similar threshold of salinity in the
      relative contribution of macrozoobenthos on nestedness. CONCLUSIONS: The use of
      detailed (ABC and Whittaker plots) and macroscopic (Simpson index and nestedness)
      approaches is proposed to identify thresholds in the structuring and functioning
      of detritus-based community of disused aquatic ecosystems: in particular, the
      inclusion of the parameter of biomass (scarcely utilized in community-based
      research) appears crucial. The responses of macrozoobenthic assemblages to the
      salinity stress conditions, in term of abundance and biomass, using a detritus
      food source (Phragmites australis leaves), may also highlight, by comparing
      macroscopic and detailed approaches, structuring and functioning patterns to
      consider for the management of disused artificial ecosystems.

PMID- 24308821
TI  - Effects of eye movement desensitization and reprocessing (EMDR) treatment in
      chronic pain patients: a systematic review.
AB  - OBJECTIVE: This study systematically reviewed the evidence regarding the effects
      of eye movement desensitization and reprocessing (EMDR) therapy for treating
      chronic pain. DESIGN: Systematic review. METHODS: We screened MEDLINE, EMBASE,
      the Cochrane Library, CINHAL Plus, Web of Science, PsycINFO, PSYNDEX, the
      Francine Shapiro Library, and citations of original studies and reviews. All
      studies using EMDR for treating chronic pain were eligible for inclusion in the
      present study. The main outcomes were pain intensity, disability, and negative
      mood (depression and anxiety). The effects were described as standardized mean
      differences. RESULTS: Two controlled trials with a total of 80 subjects and 10
      observational studies with 116 subjects met the inclusion criteria. All of these
      studies assessed pain intensity. In addition, five studies measured disability,
      eight studies depression, and five studies anxiety. Controlled trials
      demonstrated significant improvements in pain intensity with high effect sizes
      (Hedges' g: -6.87 [95% confidence interval (CI95 ): -8.51, -5.23] and -1.12 [CI95
      : -1.82, -0.42]). The pretreatment/posttreatment effect size calculations of the
      observational studies revealed that the effect sizes varied considerably, ranging
      from Hedges' g values of -0.24 (CI95 : -0.88, 0.40) to -5.86 (CI95 : -10.12, 
      1.60) for reductions in pain intensity, -0.34 (CI95 : -1.27, 0.59) to -3.69 (CI95
      : -24.66, 17.28) for improvements in disability, -0.57 (CI95 : -1.47, 0.32) to 
      1.47 (CI95 : -3.18, 0.25) for improvements in depressive symptoms, and -0.59
      (CI95 : -1.05, 0.13) to -1.10 (CI95 : -2.68, 0.48) for anxiety. Follow-up
      assessments showed maintained improvements. No adverse events were reported.
      CONCLUSIONS: Although the results of our study suggest that EMDR may be a safe
      and promising treatment option in chronic pain conditions, the small number of
      high-quality studies leads to insufficient evidence for definite treatment
      recommendations.

PMID- 24308822
TI  - Prescribing of phosphodiesterase-5 inhibitors among psychiatrists.

PMID- 24308823
TI  - Will is not enough: coping planning and action control as mediators in the
      prediction of fruit and vegetable intake.
AB  - OBJECTIVES: This study investigates the joint role of coping planning and action
      control as volitional predictors of changes in the daily consumption of fruit and
      vegetables. DESIGN: In a longitudinal online survey, 203 participants completed
      assessments at baseline (Time 1), 1 week (Time 2), and 2 weeks later (Time 3).
      METHODS: Structural equation modelling was used to test a series of three nested
      models. In Model 1, only intention predicted behaviour; in Model 2, both coping
      planning and action control were tested as mediators between intention and
      behaviour; and Model 3 specified coping planning and action control as sequential
      mediators between intention and behaviour. RESULTS: Model 3 provided the best fit
      to the data. The mediating role of coping planning and action control between
      intention and fruit and vegetable intake was confirmed, whereby multiple
      mediation occurred in a sequential manner, with coping planning preceding action
      control. CONCLUSIONS: For motivated individuals who are not yet following the
      recommendations for fruit and vegetable consumption, coping planning and action
      control reflect a psychological mechanism that operates in changes in fruit and
      vegetable consumption. Statement of contribution What is already known on this
      subject? Intention formation might not be enough to change complex health
      behaviours, such as dietary behaviours. Volitional factors - Such as action
      planning - Have shown to be important for the translation of intentions into
      behaviour, particularly for fruit and vegetable intake. Other volitional factors
      such as coping planning and action control have been less studied as potential
      mediators between intention and fruit and vegetable intake. What does this study
      add? This study provides further evidence on the psychological mechanisms of
      fruit and vegetable intake. Coping planning and action control are shown to act
      jointly in the prediction of fruit and vegetable intake. A double mediation was
      found, attesting the translation of intention into fruit and vegetable intake
      sequentially by coping planning and action control.

PMID- 24308824
TI  - Ultrasensitive size-selection of plasmonic nanoparticles by Fano interference
      optical force.
AB  - In this paper, we propose a solution for the ultrasensitive optical selection of
      plasmonic nanoparticles using Fano interference-induced scattering forces. Under
      a Gaussian beam excitation, the scattering of a plasmonic nanoparticle at its
      Fano resonance becomes strongly asymmetric in the lateral direction and
      consequently results in a net transverse scattering force, that is, Fano
      interference-induced force. The magnitude of this transverse scattering force is
      comparable with the gradient force in conventional optical manipulation
      experiments. More interestingly, the Fano scattering force is ultrasensitive to
      the particle size and excitation frequency due to the phase sensitivity of the
      interference between adjacent plasmon modes in the particle. Utilizing this
      distinct feature, we show the possibility of size-selective sorting of silver and
      gold nanoparticles with an accuracy of about +/-10 nm and silica-gold core-shell
      nanoparticles with shell thickness down to several nanometers. These results
      would add to the toolbox of optical manipulation and fabrication. 

PMID- 24308825
TI  - Pyroptosis and adaptive immunity mechanisms are promptly engendered in mesenteric
      lymph-nodes during pig infections with Salmonella enterica serovar Typhimurium.
AB  - In this study, we explored the transcriptional response and the morphological
      changes occurring in porcine mesenteric lymph-nodes (MLN) along a time course of
      1, 2 and 6 days post infection (dpi) with Salmonella Typhimurium. Additionally,
      we analysed the expression of some Salmonella effectors in tissue to complete our
      view of the processes triggered in these organs upon infection. The results
      indicate that besides dampening apoptosis, swine take advantage of the flagellin
      and prgJ expression by Salmonella Typhimuriun to induce pyroptosis in MLN,
      preventing bacterial dissemination. Furthermore, cross-presentation of Salmonella
      antigens was inferred as a mechanism that results in a rapid clearance of
      pathogen by cytotoxic T cells. In summary, although the Salmonella Typhimurium
      strain employed in this study was able to express some of its major virulence
      effectors in porcine MLN, a combination of early innate and adaptive immunity
      mechanisms might overcome virulence strategies employed by the pathogen, enabling
      the host to protect itself against bacterial spread beyond gut-associated lymph
      nodes. Interestingly, we deduced that clathrin-mediated endocytosis could
      contribute to mechanisms of pathogen virulence and/or host defence in MLN of
      Salmonella infected swine. Taken together, our results are useful for a better
      understanding of the critical protective mechanisms against Salmonella that occur
      in porcine MLN to prevent the spread of infection beyond the intestine.

PMID- 24308826
TI  - RoKSN, a floral repressor, forms protein complexes with RoFD and RoFT to regulate
      vegetative and reproductive development in rose.
AB  - FT/TFL1 family members have been known to be involved in the development and
      flowering in plants. In rose, RoKSN, a TFL1 homologue, is a key regulator of
      flowering, whose absence causes continuous flowering. Our objectives are to
      functionally validate RoKSN and to explore its mode of action in rose. We
      complemented Arabidopsis tfl1 mutants and ectopically expressed RoKSN in a
      continuous-flowering (CF) rose. Using different protein interaction techniques,
      we studied RoKSN interactions with RoFD and RoFT and possible competition. In
      Arabidopsis, RoKSN complemented the tfl1 mutant by rescuing late flowering and
      indeterminate growth. In CF roses, the ectopic expression of RoKSN led to the
      absence of flowering. Different branching patterns were observed and some
      transgenic plants had an increased number of leaflets per leaf. In these
      transgenic roses, floral activator transcripts decreased. Furthermore, RoKSN was
      able to interact both with RoFD and the floral activator, RoFT. Protein
      interaction experiments revealed that RoKSN and RoFT could compete with RoFD for
      repression and activation of blooming, respectively. We conclude that RoKSN is a
      floral repressor and is also involved in the vegetative development of rose.
      RoKSN forms a complex with RoFD and could compete with RoFT for repression of
      flowering. 

PMID- 24308827
TI  - No association between serum cholesterol and death by suicide in patients with
      schizophrenia, bipolar affective disorder, or major depressive disorder.
AB  - BACKGROUND: Previous research on serum total cholesterol and suicidality has
      yielded conflicting results. Several studies have reported a link between low
      serum total cholesterol and suicidality, whereas others have failed to replicate
      these findings, particularly in patients with major affective disorders. These
      discordant findings may reflect the fact that studies often do not distinguish
      between patients with bipolar and unipolar depression; moreover, definitions and
      classification schemes for suicide attempts in the literature vary widely.
      METHODS: Subjects were patients with one of the three major psychiatric disorders
      commonly associated with suicide: schizophrenia, bipolar affective disorder, and
      major depressive disorder (MDD). We compared serum lipid levels in patients who
      died by suicide (82 schizophrenia, 23 bipolar affective disorder, and 67 MDD) and
      non-suicide controls (200 schizophrenia, 49 bipolar affective disorder, and 175
      MDD). RESULTS: Serum lipid profiles did not differ between patients who died by
      suicide and control patients in any diagnostic group. CONCLUSIONS: Our results do
      not support the use of biological indicators such as serum total cholesterol to
      predict suicide risk among patients with a major psychiatric disorder.

PMID- 24308829
TI  - Using eye tracking to identify faking attempts during penile plethysmography
      assessment.
AB  - Penile plethysmography (PPG) is considered the most rigorous method for sexual
      interest assessment. Nevertheless, it is subject to faking attempts by
      participants, which compromises the internal validity of the instrument. To date,
      various attempts have been made to limit voluntary control of sexual response
      during PPG assessments, without satisfactory results. This exploratory research
      examined eye-tracking technologies' ability to identify the presence of cognitive
      strategies responsible for erectile inhibition during PPG assessment. Eye
      movements and penile responses for 20 subjects were recorded while exploring
      animated human-like computer-generated stimuli in a virtual environment under
      three distinct viewing conditions: (a) the free visual exploration of a preferred
      sexual stimulus without erectile inhibition; (b) the viewing of a preferred
      sexual stimulus with erectile inhibition; and (c) the free visual exploration of
      a non-preferred sexual stimulus. Results suggest that attempts to control
      erectile responses generate specific eye-movement variations, characterized by a
      general deceleration of the exploration process and limited exploration of the
      erogenous zone. Findings indicate that recording eye movements can provide
      significant information on the presence of competing covert processes responsible
      for erectile inhibition. The use of eye-tracking technologies during PPG could
      therefore lead to improved internal validity of the plethysmographic procedure. 

PMID- 24308830
TI  - Crack formation under an electric field in droplets of laponite gel: memory
      effect and scaling relations.
AB  - When a colloidal gel dries through evaporation, cracks are usually formed, which
      often reveal underlying processes at work during desiccation. Desiccating colloid
      droplets of a few hundred microliters size show interesting effects of pattern
      formation and cracking which makes this an active subject of current research.
      Because aqueous gels of clay are known to be strongly affected by an electric
      field, one may expect crack patterns to exhibit a field effect. In the present
      study we allow droplets of laponite gel to dry under a radial electric field.
      This gives rise to highly reproducible patterns of cracks, which depend on the
      strength, direction, and time of exposure to the electric field. For a
      continuously applied DC voltage, cracks always appear on dissipation of a certain
      constant amount of energy. If the field is switched off before cracks appear, the
      observed results are shown to obey a number of empirical scaling relations, which
      enable us to predict the time of appearance and the number of cracks under
      specified conditions. Scanning electron microscopy (SEM) images of the surface
      between the macroscopic cracks show the presence of microcracks, which are wider
      and more numerous when no electric field is applied. The microcracks are reduced
      in the presence of stronger fields. 

PMID- 24308831
TI  - Postpartum fever in the presence of a fibroid: Sphingomonas paucimobilis sepsis
      associated with pyomyoma.
AB  - BACKGROUND: Pyomyoma is a life-threatening complication of uterine leiomyoma. It
      may occur in post- menopausal women, during pregnancy and in the postpartum
      period. Fever may be the only manifestation during the early stages of the
      disease. We detail the first reported case of postpartum pyomyoma-related sepsis
      due to Sphingomonas paucimobilis, a Gram-negative bacillus that is gaining
      recognition as an important human pathogen. CASE PRESENTATION: A woman presented
      with an asymptomatic uterine fibroid and a two-week history of fever during the
      postpartum period. Suppurative uterine leiomyoma was diagnosed, and blood
      cultures grew Sphingomonas paucimobilis. The myoma was surgically removed from
      the uterus without hysterectomy. Intravenous antimicrobial therapy was given for
      fifteen days, and the patient was discharged from hospital in good condition.
      CONCLUSION: Pyomyoma should be considered in broad differential diagnosis of
      postpartum fever. This case highlights a unique disease manifestation of S.
      paucimobilis, an emerging opportunistic pathogen with increasing significance in
      the nosocomial setting.

PMID- 24308832
TI  - Anakinra for cryopyrin-associated periodic syndrome.
AB  - Cryopyrin-associated periodic syndrome (CAPS) is a very rare auto-inflammatory
      syndrome, which has recently served as a pure model of IL-1beta-driven diseases.
      CAPS is caused by mutations into the NLRP3 gene that encodes crypoyrin, which
      serves as a receptor of the innate immunity that senses danger signals and
      pathogens. Constitutive activation of cryopyrin in CAPS leads to an excessive
      secretion of IL-1beta. CAPS patients experience symptoms of systemic
      inflammation, intense fatigue and have poor quality of life. In the most severe
      forms, they may develop serious organ damage such as visual and hearing
      impairment, neurological deterioration and renal insufficiency. Anti-IL-1 drugs
      are effective in treating symptoms of almost all CAPS patients and have radically
      transformed their lives. We describe the history of the 'revival' of CAPS
      patients through anti-IL-1 treatments with a special focus on anakinra, the first
      drug used in cohorts with variable disease severity and number of patients. 

PMID- 24308833
TI  - Immunomodulation of malignant melanoma by contact sensitizing agents.
AB  - The importance of host defense against malignant melanoma is underlined by the
      use of immunomodulating agents as effective therapies. Diphencyprone and 2,4
      dinitrochlorobenzene (DNCB) have been used successfully as contact sensitizing
      agents in this regard. Through haptenation of cell surface and cytoplasmic
      proteins, these agents trigger a CD8(+) T-lymphocyte predominant allergic contact
      hypersensitivity response. Th17 cells may also play a critical role. The
      effectiveness of these agents at stimulating tumor defense may be limited to
      melanoma of the skin. Response to immunotherapy using diphencyprone and DNCB is
      governed by the immune status of the host, which is affected by tumor burden, UV
      light and age. Additionally, diphencyprone and DNCB elicit synergy with other
      methods of treatment and thus may be used as adjuncts. Two current prospective
      trials may aid in elucidating the impact that this treatment modality has on the
      prognosis and quality of life of patients with melanoma. 

PMID- 24308834
TI  - Immunoglobulin class switch recombination deficiency type 1 or CD40 ligand
      deficiency: from bedside to bench and back again.
AB  - The immunoglobulin class switch recombination deficiency or hyper-IgM syndrome is
      characterized by normal or elevated serum IgM and low serum levels of other
      immunoglobulins. Since the first reported patient with hyper-IgM, more than 200
      patients with this phenotype resulted from CD40 ligand deficiency have been
      reported. However, in addition to this common finding, they presented with
      different manifestations like opportunistic infections, autoimmunity and
      malignancies each of them are worth a detailed look. In this review, we will
      focus on different underlying mechanisms of these presentations to review what we
      have learned from our patients. In the end, we will discuss different treatment
      options available for these patients using this knowledge. 

PMID- 24308835
TI  - Stem cell transplantation in the context of HIV--how can we cure HIV infection?
AB  - All HIV target cells are derived from hematopoietic stem cells. More than two
      decades ago, a hypothesis was postulated that a cure for HIV may be possible by
      performing a transplant with HIV-resistant hematopoietic stem cells that would
      allow for an HIV-resistant immune system to arise. HIV-resistant stem cells could
      be generated by genetically modifying them with gene therapy vectors transferring
      anti-HIV genes. First attempts of stem cell gene therapy for HIV were carried out
      in the USA in the 1990s demonstrating safety, but also little efficacy at that
      time. The first demonstration that the postulated hypothesis was correct was the
      cure of an HIV-infected individual in Berlin in 2009 who received an allogeneic
      bone marrow transplant from a donor who lacked the CCR5 chemokine receptor, a
      naturally arising mutation rendering HIV target cells resistant to infection with
      macrophage tropic strains of HIV. In 2013, reports were published about a
      possible cure of HIV-infected individuals who received allogeneic bone marrow
      transplants with cells not resistant to HIV. We will review these stem cell
      transplant procedures and discuss their utility to provide a cure for HIV
      infection, including efficacious future stem cell gene therapy applications. 

PMID- 24308837
TI  - The intelligent use of systemic glucocorticoids in rheumatoid arthritis.
AB  - Glucocorticoids (GC) have potent anti-inflammatory and immunomodulatory effects
      and are widely used in the management of rheumatoid arthritis in combination with
      other disease-modifying anti-rheumatoid drugs. Concern about the risk of adverse
      effects may be to some extent misplaced as low to moderate doses of GC have
      different mechanisms of action and risk profiles compared with high doses. This
      review discusses the current understanding about the different modes of action of
      GC, their strong disease-modifying properties and the efforts at improving the
      therapeutic ratio of GC through the development of new drugs which promise
      greater safety such as selective GC receptor agonists, liposomal GC and modified
      release (MR) prednisone. 

PMID- 24308838
TI  - The interplay between the immune system and chemotherapy: emerging methods for
      optimizing therapy.
AB  - Preclinical studies have revealed an unexpected ability of the immune system to
      contribute to the success of chemotherapy and radiotherapy. Anticancer therapies
      can trigger immune system activation by promoting the release of danger signals
      from dying tumor cells and/or the elimination of immunosuppressive cells. We
      have, however, recently discovered that some chemotherapies, such as 5
      fluorouracil and gemcitabine, exert conflicting effects on anticancer immune
      responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived
      suppressive cells in tumor-bearing rodents, these chemotherapies promoted the
      release of IL-1beta and the development of pro-angiogenic IL-17-producing CD4 T
      cells. The ambivalent effects of chemotherapy on immune responses should thus be
      carefully considered to design effective combination therapies based on
      chemotherapy and immune modulators. Herein, we discuss how the initial findings
      underscoring the key role of the immune system in mediating the antitumor
      efficacy of anticancer agents could begin to translate into effective therapies
      in humans. 

PMID- 24308836
TI  - Understanding the role of B cells in atherosclerosis: potential clinical
      implications.
AB  - Atherosclerosis is a progressive inflammatory disease of the medium to large
      arteries that is the largest contributor to cardiovascular disease. B-cell
      subsets have been shown in animal models of atherosclerosis to have both
      atherogenic and atheroprotective properties. In this review, we highlight the
      research that developed our understanding of the role of B cells in
      atherosclerosis both in humans and mice. From this we discuss the potential
      clinical impact B cells could have both as diagnostic biomarkers and as targets
      for immunotherapy. Finally, we recognize the inherent difficulty in translating
      findings from animal models into humans given the differences in both
      cardiovascular disease and the immune system between mice and humans, making the
      case for greater efforts at addressing the role of B cells in human
      atherosclerosis. 

PMID- 24308839
TI  - Estrogen's effects in chronic autoimmune/inflammatory diseases and progression to
      cancer.
AB  - Endocrine-immune system interactions are the basis for predominance of autoimmune
      diseases in women with differences between the fertile and the postmenopausal
      periods. B cell-driven diseases reach the maximum incidence rate in the
      reproductive years, at least in women under the effects of serum estrogens and
      their metabolites (endocrine synthesis). On the other hand, the prevalent
      peripheral synthesis of estrogens, especially in advanced ages (intracrine
      synthesis), through the action of aromatases, modulate the immune/inflammatory
      response in peripheral tissues similarly in both female and male patients (final
      common pathway). Interestingly, tissue injury that occurs during chronic
      immune/inflammatory reaction induces tissue repair and homeostatic responses
      including cell proliferation, growth factor production and angiogenesis that
      might facilitate cancer progression. The successful treatment of chronic
      immune/inflammatory diseases obtained by using medications initially developed
      for use in oncology, such as antiproliferative drugs, B-cell depleting monoclonal
      antibodies support the inflammation-cancer link. 

PMID- 24308842
TI  - Synthesis of N-acyl-N,O-acetals mediated by titanium ethoxide.
AB  - N-Acyl-N,O-acetals are present in a number of bioactive natural products, and
      this unusual functional group can act as a synthetic precursor to unstable
      reactive N-acylimines. In this paper, a variety of N-acyl-O-ethyl-N,O-acetals was
      concisely prepared under mild conditions mediated by titanium ethoxide
      (Ti(OEt)4). The method also offers a new strategy to make other O-alkyl-N,O
      acetals. Furthermore, this strategy was extended to the synthesis of an analogue
      of the natural product turtschamide. 

PMID- 24308840
TI  - LE135, a retinoid acid receptor antagonist, produces pain through direct
      activation of TRP channels.
AB  - BACKGROUND AND PURPOSE: Retinoids, through their activation of retinoic acid
      receptors (RARs) and retinoid X receptors, regulate diverse cellular processes,
      and pharmacological intervention in their actions has been successful in the
      treatment of skin disorders and cancers. Despite the many beneficial effects,
      administration of retinoids causes irritating side effects with unknown
      mechanisms. Here, we demonstrate that LE135 [4-(7,8,9,10-tetrahydro-5,7,7,10,10
      pentamethyl-5H-benzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid], a
      selective antagonist of RARbeta , is a potent activator of the capsaicin (TRPV1)
      and wasabi (TRPA1) receptors, two critical pain-initiating cation channels.
      EXPERIMENTAL APPROACH: We performed to investigate the excitatory effects of
      LE135 on TRPV1 and TRPA1 channels expressed in HEK293T cells and in dorsal root
      ganglia neurons with calcium imaging and patch-clamp recordings. We also used
      site-directed mutagenesis of the channels to determine the structural basis of
      LE135-induced activation of TRPV1 and TRPA1 channels and behavioural testing to
      examine if pharmacological inhibition and genetic deletion of the channels
      affected LE135-evoked pain-related behaviours. KEY RESULTS: LE135 activated both
      the capsaicin receptor (TRPV1) and the allyl isothiocyanate receptor (TRPA1)
      heterologously expressed in HEK293T cells and endogenously expressed by sensory
      nociceptors. Mutations disrupting the capsaicin-binding site attenuated LE135
      activation of TRPV1 channels and a single mutation (K170R) eliminated TRPA1
      activity evoked by LE135. Intraplantar injection of LE135 evoked pain-related
      behaviours. Both TRPV1 and TRPA1 channels were involved in LE135-elicited pain
      related responses, as shown by pharmacological and genetic ablation studies.
      CONCLUSIONS AND IMPLICATIONS: This blocker of retinoid acid signalling also
      exerted non-genomic effects through activating the pain-initiating TRPV1 and
      TRPA1 channels.

PMID- 24308841
TI  - Transcriptional profile of Salmonella enterica subsp. enterica serovar
      Weltevreden during alfalfa sprout colonization.
AB  - Sprouted seeds represent a great risk for infection by human enteric pathogens
      because of favourable growth conditions for pathogens during their germination.
      The aim of this study was to identify mechanisms of interactions of Salmonella
      enterica subsp. enterica Weltevreden with alfalfa sprouts. RNA-seq analysis of S.
      Weltevreden grown with sprouts in comparison with M9-glucose medium showed that
      among a total of 4158 annotated coding sequences, 177 genes (4.3%) and 345 genes
      (8.3%) were transcribed at higher levels with sprouts and in minimal medium
      respectively. Genes that were higher transcribed with sprouts are coding for
      proteins involved in mechanisms known to be important for attachment, motility
      and biofilm formation. Besides gene expression required for phenotypic adaption,
      genes involved in sulphate acquisition were higher transcribed, suggesting that
      the surface on alfalfa sprouts may be poor in sulphate. Genes encoding structural
      and effector proteins of Salmonella pathogenicity island 2, involved in survival
      within macrophages during infection of animal tissue, were higher transcribed
      with sprouts possibly as a response to environmental conditions. This study
      provides insight on additional mechanisms that may be important for pathogen
      interactions with sprouts. 

PMID- 24308843
TI  - Surface functionalization of thin-film composite membranes with copper
      nanoparticles for antimicrobial surface properties.
AB  - Biofouling is a major operational challenge in reverse osmosis (RO) desalination,
      motivating a search for improved biofouling control strategies. Copper, long
      known for its antibacterial activity and relatively low cost, is an attractive
      potential biocidal agent. In this paper, we present a method for loading copper
      nanoparticles (Cu-NPs) on the surface of a thin-film composite (TFC) polyamide RO
      membrane. Cu-NPs were synthesized using polyethyleneimine (PEI) as a capping
      agent, resulting in particles with an average radius of 34 nm and a copper
      content between 39 and 49 wt.%. The positive charge of the Cu-NPs imparted by the
      PEI allowed a simple electrostatic functionalization of the negatively charged RO
      membrane. We confirmed functionalization and irreversible binding of the Cu-NPs
      to the membrane surface with SEM and XPS after exposing the membrane to bath
      sonication. We also demonstrated that Cu-NP functionalization can be repeated
      after the Cu-NPs dissolve from the membrane surface. The Cu-NP functionalization
      had minimal impact on the intrinsic membrane transport parameters. Surface
      hydrophilicity and surface roughness were also maintained, and the membrane
      surface charge became positive after functionalization. The functionalized
      membrane exhibited significant antibacterial activity, leading to an 80-95%
      reduction in the number of attached live bacteria for three different model
      bacterial strains. Challenges associated with this functionalization method and
      its implementation in RO desalination are discussed. 

PMID- 24308845
TI  - Testing the utility of three social-cognitive models for predicting objective and
      self-report physical activity in adults with type 2 diabetes.
AB  - OBJECTIVE: Theory-based interventions to promote physical activity (PA) are more
      effective than atheoretical approaches; however, the comparative utility of
      theoretical models is rarely tested in longitudinal designs with multiple time
      points. Further, there is limited research that has simultaneously tested social
      cognitive models with self-report and objective PA measures. The primary aim of
      this study was to test the predictive ability of three theoretical models (social
      cognitive theory, theory of planned behaviour, and protection motivation theory)
      in explaining PA behaviour. METHODS: Participants were adults with type 2
      diabetes (n = 287, 53.8% males, mean age = 61.6 +/- 11.8 years). Theoretical
      constructs across the three theories were tested to prospectively predict PA
      behaviour (objective and self-report) across three 6-month time intervals
      (baseline-6, 6-12, 12-18 months) using structural equation modelling. PA outcomes
      were steps/3 days (objective) and minutes of MET-weighted PA/week (self-report).
      RESULTS: The mean proportion of variance in PA explained by these models was 6.5%
      for objective PA and 8.8% for self-report PA. Direct pathways to PA outcomes were
      stronger for self-report compared with objective PA. CONCLUSIONS: These theories
      explained a small proportion of the variance in longitudinal PA studies. Theory
      development to guide interventions for increasing and maintaining PA in adults
      with type 2 diabetes requires further research with objective measures. Theory
      integration across social-cognitive models and the inclusion of ecological levels
      are recommended to further explain PA behaviour change in this population.
      Statement of contribution What is already known on this subject? Social-cognitive
      theories are able to explain partial variance for physical activity (PA)
      behaviour. What does this study add? The testing of three theories in a
      longitudinal design over 3, 6-month time intervals. The parallel use and
      comparison of both objective and self-report PA measures in testing these
      theories.

PMID- 24308846
TI  - The effectiveness and risks of fluoroscopically guided cervical transforaminal
      injections of steroids: a systematic review with comprehensive analysis of the
      published data.
AB  - OBJECTIVE: To determine the effectiveness and risks of fluoroscopically guided
      cervical transforaminal injection of corticosteroids in the treatment of
      radicular pain. DESIGN: Systematic review of the literature with comprehensive
      analysis of the published data. INTERVENTIONS: Three reviewers with formal
      training in evidence-based medicine searched the literature on fluoroscopically
      guided cervical transforaminal injection of steroids (CTFIS). Each reviewer
      independently assessed the methodology of studies found and appraised the quality
      of the evidence presented. OUTCOME MEASURES: The primary outcome assessed was
      relief of radicular pain. Other outcomes such as reduction in surgery rate and
      complications were noted if reported. The evidence on each outcome was appraised
      in accordance with the Grades of Recommendation, Assessment, Development, and
      Evaluation (GRADE) system of evaluating evidence. RESULTS: The searches yielded
      16 primary publications on effectiveness. Available evidence, derived mainly from
      observational studies, suggests that approximately 50% of patients experience 50%
      relief of radicular pain for at least 4 weeks after CTFIS, and the intervention
      may have surgery-sparing effects. The literature also contains 21 articles with
      primary reports of serious complications, including 13 deaths and many
      catastrophic neurological injuries. The evidence of pain-relieving effects, of
      surgery-sparing effects, and of risks of CTFIS were all rated as of very low
      quality according to the GRADE system. CONCLUSIONS: In patients with cervical
      radicular pain, fluoroscopically guided CTFIS may be effective in easing pain and
      reducing need for surgery. However, the evidence of effectiveness is of very low
      quality, and the benefits of the procedure are compromised by the risks of
      serious complications.

PMID- 24308844
TI  - Molecular origin of the binding of WWOX tumor suppressor to ErbB4 receptor
      tyrosine kinase.
AB  - The ability of WWOX tumor suppressor to physically associate with the
      intracellular domain (ICD) of ErbB4 receptor tyrosine kinase is believed to play
      a central role in downregulating the transcriptional function of the latter.
      Herein, using various biophysical methods, we show that while the WW1 domain of
      WWOX binds to PPXY motifs located within the ICD of ErbB4 in a physiologically
      relevant manner, the WW2 domain does not. Importantly, while the WW1 domain
      absolutely requires the integrity of the PPXY consensus sequence, nonconsensus
      residues within and flanking this motif do not appear to be critical for binding.
      This strongly suggests that the WW1 domain of WWOX is rather promiscuous toward
      its cellular partners. We also provide evidence that the lack of binding of the
      WW2 domain of WWOX to PPXY motifs is due to the replacement of a signature
      tryptophan, lining the hydrophobic ligand binding groove, with tyrosine (Y85).
      Consistent with this notion, the Y85W substitution within the WW2 domain
      exquisitely restores its binding to PPXY motifs in a manner akin to the binding
      of the WW1 domain of WWOX. Of particular significance is the observation that the
      WW2 domain augments the binding of the WW1 domain to ErbB4, implying that the
      former serves as a chaperone within the context of the WW1-WW2 tandem module of
      WWOX in agreement with our findings reported previously. Altogether, our study
      sheds new light on the molecular basis of an important WW-ligand interaction
      involved in mediating a plethora of cellular processes. 

PMID- 24308847
TI  - Effects of bisphosphonate on oxidative stress levels in patients with different
      types of cancer.
AB  - We investigated the effects of bisphosphonate (BP) on oxidative stress levels in
      blood of patients with cancer. In total, 19 patients with cancer and 21 healthy
      subjects were included in the study. BP was intravenously administrated to the
      participants for 6 weeks. The patients had higher lipid peroxidation (LP) levels
      in the plasma and erythrocyte samples but lower glutathione peroxidase (GSH-Px)
      and plasma vitamin E values. In patients treated with BP, calcium and LP levels
      decreased, but GSH-Px and vitamin E values improved. In conclusion, we observed
      that treatment with BP alleviated oxidative stress induced by cancer. 

PMID- 24308848
TI  - BNCI systems as a potential assistive technology: ethical issues and
      participatory research in the BrainAble project.
AB  - PURPOSE: This paper highlights aspects related to current research and thinking
      about ethical issues in relation to Brain Computer Interface (BCI) and Brain
      Neuronal Computer Interfaces (BNCI) research through the experience of one
      particular project, BrainAble, which is exploring and developing the potential of
      these technologies to enable people with complex disabilities to control
      computers. It describes how ethical practice has been developed both within the
      multidisciplinary research team and with participants. RESULTS: The paper
      presents findings in which participants shared their views of the project
      prototypes, of the potential of BCI/BNCI systems as an assistive technology, and
      of their other possible applications. This draws attention to the importance of
      ethical practice in projects where high expectations of technologies, and
      representations of "ideal types" of disabled users may reinforce stereotypes or
      drown out participant "voices". CONCLUSIONS: Ethical frameworks for research and
      development in emergent areas such as BCI/BNCI systems should be based on broad
      notions of a "duty of care" while being sufficiently flexible that researchers
      can adapt project procedures according to participant needs. They need to be
      frequently revisited, not only in the light of experience, but also to ensure
      they reflect new research findings and ever more complex and powerful
      technologies.

PMID- 24308849
TI  - Input-output relations in biological systems: measurement, information and the
      Hill equation.
AB  - Biological systems produce outputs in response to variable inputs. Input-output
      relations tend to follow a few regular patterns. For example, many chemical
      processes follow the S-shaped Hill equation relation between input concentrations
      and output concentrations. That Hill equation pattern contradicts the fundamental
      Michaelis-Menten theory of enzyme kinetics. I use the discrepancy between the
      expected Michaelis-Menten process of enzyme kinetics and the widely observed Hill
      equation pattern of biological systems to explore the general properties of
      biological input-output relations. I start with the various processes that could
      explain the discrepancy between basic chemistry and biological pattern. I then
      expand the analysis to consider broader aspects that shape biological input
      output relations. Key aspects include the input-output processing by component
      subsystems and how those components combine to determine the system's overall
      input-output relations. That aggregate structure often imposes strong regularity
      on underlying disorder. Aggregation imposes order by dissipating information as
      it flows through the components of a system. The dissipation of information may
      be evaluated by the analysis of measurement and precision, explaining why certain
      common scaling patterns arise so frequently in input-output relations. I discuss
      how aggregation, measurement and scale provide a framework for understanding the
      relations between pattern and process. The regularity imposed by those broader
      structural aspects sets the contours of variation in biology. Thus, biological
      design will also tend to follow those contours. Natural selection may act
      primarily to modulate system properties within those broad constraints.

PMID- 24308850
TI  - Welfare implication of measuring heart rate and heart rate variability in dairy
      cattle: literature review and conclusions for future research.
AB  - Heart rate (HR) measurements have been used to determine stress in livestock
      species since the beginning of the 1970s. However, according to the latest
      studies in veterinary and behaviour-physiological sciences, heart rate
      variability (HRV) proved to be more precise for studying the activity of the
      autonomic nervous system. In dairy cattle, HR and HRV indices have been used to
      detect stress caused by routine management practices, pain or milking. This
      review provides the significance of HR and HRV measurements in dairy cattle by
      summarising current knowledge and research results in this area. First, the
      biological background and the interrelation of the autonomic regulation of
      cardiovascular function, stress, HR and HRV are discussed. Equipment and
      methodological approaches developed to measure interbeat intervals and estimate
      HRV in dairy cattle are described. The methods of HRV analysis in time, frequency
      and non-linear domains are also explained in detail emphasising their
      physiological background. Finally, the most important scientific results and
      potential possibilities for future research are presented. 

PMID- 24308851
TI  - A multicenter quasi-experimental study: impact of a central line infection
      control program using auditing and performance feedback in five Belgian intensive
      care units.
AB  - BACKGROUND: We analyzed the impact associated with an intervention based on
      process control and performance feedback to decrease central line-associated
      bloodstream infection (CLABSI) rates.This study was conducted from March 2011 to
      September 2012 in five adult intensive care units (ICU) located in two Belgian
      tertiary hospitals A and B, with a total of 53 beds. METHODS: This study was
      divided in three phases: P1 (baseline), P2 (intervention) and P3 (post
      intervention).During P2, external monitoring of five central venous catheters
      (CVC) care critical processes and monthly reporting (meetings and feedbacks
      reports posted) of performance indicators (CLABSI rate, CVC utilization ratio,
      compliance rate with each care process, and insertion site) to ICU workers were
      performed. The external monitoring of process measures was assessed by the same
      trained research nurse.A Poisson regression analysis was used to compare CLABSI
      incidence density rate per phase. Statistical significance was achieved with 2
      sided p-value of <0.05. For the analysis, we separated the five ICU in hospital A
      and B when appropriate. RESULTS: Significantly improved total mean compliance was
      achieved for hand hygiene, CVC handling and CVC dressing. CLABSI rate declined
      from 4.00 (95% confidence interval (CI): 1.94-6.06) to 1.81 (0.46-3.17) per 1,000
      CVC-days in P2 with an incidence rate ratio (IRR) of 0.49 (0.24-0.98, p = 0.043).
      A better response was observed in hospital A where the nurse participation at the
      monthly meeting was significantly higher than in hospital B (p < 0.001) as the
      percentage of feedbacks reports posted in ICU (p < 0.001). The decline in the
      CLABSI rate observed during P2 in comparison with P1 was independent of the
      insertion site (femoral or non-femoral; p = 0.054). The overall CLABSI rate
      increased to 2.73 (1.17-4.29) per 1,000 CVC-days with IRR of 0.67 (0.36-1.26, p =
      0.212) in P3 compared to P1, but a high nursing turnover was observed in both
      hospitals. CONCLUSIONS: Our intervention focused on external auditing and
      performance feedback resulted in significant reduction in rates of CLABSI.
      Investigation continues regarding the most effective way to sustain CLABSI
      prevention practices and to improve the culture of safety in healthcare.

PMID- 24308852
TI  - RNase HI stimulates the activity of RnlA toxin in Escherichia coli.
AB  - A type II toxin-antitoxin system in Escherichia coli, rnlA-rnlB, functions as an
      anti-phage mechanism. RnlA is a toxin with an endoribonuclease activity and the
      cognate RnlB inhibits RnlA toxicity in E. coli cells. After bacteriophage T4
      infection, RnlA is activated by the disappearance of RnlB, resulting in the rapid
      degradation of T4 mRNAs and consequently no T4 propagation, when T4 dmd is
      defective: Dmd is an antitoxin against RnlA for promoting own propagation.
      Previous studies suggested that the activation of RnlA after T4 infection was
      regulated by multiple components. Here, we provide the evidence that RNase HI is
      an essential factor for activation of RnlA. The dmd mutant phage could grow on
      DeltarnhA (encoding RNase HI) cells, in which RnlA-mediated mRNA cleavage
      activity was defective. RNase HI bound to RnlA in vivo and enhanced the RNA
      cleavage activity of RnlA in vitro. In addition, ectopic expression of RnlA in
      DeltarnlAB DeltarnhA cells has less effect on cell toxicity and RnlA-mediated
      mRNA degradation than in DeltarnlAB cells. This is the first example of a direct
      factor for activation of a toxin. 

PMID- 24308853
TI  - Comparison of two multiplex PCR assays for the detection of respiratory viral
      infections.
AB  - INTRODUCTION: Respiratory viruses are the main causes of upper and lower
      respiratory tract diseases. Rapid and accurate detection of respiratory viruses
      is crucial for appropriate patient treatment and prevention of endemic spread.
      OBJECTIVES: We compared two multiplex polymerase chain reaction (PCR) assays for
      the detection of respiratory viral pathogens. METHODS: A total of 245 respiratory
      specimens (229 sputum samples, 14 bronchoalveolar lavage samples, 6 nasal swabs,
      3 throat swabs, 7 unknown) were analyzed using two multiplex assays: One-step RV
      real-time PCR (BioSewoom, Seoul, Korea) and Seeplex RV 12 Detection kit (Seegene,
      Seoul, Korea). The results were further confirmed using sequencing as a
      reference. RESULTS: Among 245 samples (265 identifications including co
      infections), the identification of respiratory viruses was 44.9% (119/265), 44.2%
      (117/265) and 45.3% (120/265) by One-step RV assay, Seeplex RV assay and
      sequencing, respectively. The concordance rate between One-step RV assay and
      sequencing was 95.5% (253/265), and that between Seeplex RV assay and sequencing
      was 89.8% (238/265) (P = 0.0189). The sensitivities of One-step RV and Seeplex RV
      assays were 94.1% [95% confidential interval (CI), 88.3%-97.6%] and 83.3% (95%
      CI, 75.4%-89.5%), respectively (P = 0.0002). The specificities of One-step RV and
      Seeplex RV assays were 96.6% (95% CI, 92.2%-98.9%) and 95.2% (95% CI, 90.3%
      98.0%), respectively. CONCLUSION: Although the performances of One-step RV and
      Seeplex RV assays were overall comparable, One-step RV assay showed better
      sensitivity and concordance with sequencing. One-step RV assay can be a useful
      option for respiratory virus testing in clinical laboratories.

PMID- 24308854
TI  - Total synthesis of sandresolide B and amphilectolide.
AB  - The total synthesis of the diterpenoids sandresolide B and amphilectolide from a
      common furan building block is presented. Key steps include palladium-mediated
      carbonylation, lanthanide catalyzed ring closure, Myers alkylation,
      intramolecular Friedel-Crafts acylation, photooxygenation, and a Kornblum
      DeLaMare rearrangement. 

PMID- 24308855
TI  - Nurses' work-related stress in China: a comparison between psychiatric and
      general hospitals.
AB  - PURPOSE: Little is known about the level of work-related stress in nurses in
      China.This study compared the level of work-related stress between female nurses
      working in psychiatric and general hospitals in China. DESIGN AND METHODS: A
      descriptive comparative cross-sectional design was used.A consecutive sample of
      nurses from two psychiatric hospitals (N = 297) and a medical unit (N = 408) of a
      general hospital completed a written survey including socio-demographic data and
      a measure of work-related stress (Nurse Stress Inventory). FINDINGS: Compared to
      the nurses working in the general hospital, those working in the psychiatric
      setting had a higher level of stress in the domains of working environment and
      resources (p < .001) and patient care (p < .001), but lower workload and time (p
      < .001).Multivariate analyses revealed that college or higher level of
      education(b = .1, p < .001), exposure to violence in the past 6 months (b = .2, p
      < .001),longer working experience, and working in psychiatric hospitals were
      associated with high work-related stress (b = .2, p < .001). PRACTICE
      IMPLICATIONS: Considering the harmful effects of work-related stress, specific
      stress management workshops and effective staff supportive initiatives for
      Chinese nurses are warranted.

PMID- 24308856
TI  - Systematic review with meta-analysis: the association between human
      papillomavirus infection and oesophageal cancer.
AB  - BACKGROUND: Human papillomavirus (HPV) infection might be one of the potential
      risk factors for oesophageal cancer. However, the previous epidemiological
      findings were heterogeneous. AIM: To explore the association between HPV
      infection and oesophageal cancer risk by means of meta-analysis. METHODS: Studies
      on HPV infection and oesophageal cancer were identified, the prevalence of HPV
      infection and its association with oesophageal cancer risk were quantitatively
      summarised by meta-analysis. RESULTS: A total of 8990 oesophageal squamous cell
      carcinoma (SCC) patients and 174 oesophageal adenocarcinomas patients were
      evaluated from 76 included studies. Summarised HPV prevalence in oesophageal SCC
      was 22.2% [95% confidence interval (CI), 18.3-26.7%], HPV-16 was the most
      frequently observed subtype with a summarised prevalence of 11.4% (95% CI: 8.2
      15.7%). With respect to oesophageal adenocarcinoma, HPV prevalence was 35.0% (95%
      CI, 13.2-65.7%) and HPV-16 prevalence was 11.4% (95% CI: 8.2-15.7%). Due to the
      limited number of included studies on oesophageal adenocarcinoma, association
      analyses were performed to oesophageal SCC only. Significant association was
      observed between HPV infection and oesophageal SCC with a summarised odds ratio
      of 3.32 (95% CI, 2.26-4.87). According to HPV-16, the strength of the association
      was found to be 3.52 (95% CI, 2.04-6.07). CONCLUSIONS: Human papillomavirus
      infection was observed to be associated with an increased risk of oesophageal SCC
      in this meta-analysis. However, due to the evident heterogeneity observed between
      the included studies and the strength of the association not as strong as
      observed for cervical cancer and laryngeal cancer, further studies are needed to
      clarify the relation and its underlying mechanisms.

PMID- 24308858
TI  - Synthesis of heteroaryl compounds through cross-coupling reaction of aryl
      bromides or benzyl halides with thienyl and pyridyl aluminum reagents.
AB  - An efficient method for synthesis of useful biaryl building blocks containing 2
      thienyl, 3-thienyl, 2-pyridyl, and 3-pyridyl moieties was provided through cross
      coupling reactions of aryl bromides or benzyl halides with heteroaryl aluminum
      reagents in the presence of Pd(OAc)2 and (o-tolyl)3P. The coupling reaction also
      worked efficiently with heteroaryl bromides affording series of heterobiaryl
      compounds. The reaction of phenylbromide with in situ prepared 3-pyridyl aluminum
      was demonstrated to afford the product 8a in high yield. Additionally, the
      catalytic system was also suited well for the coupling reaction of benzyl halides
      with pyridyl aluminum reagents to afford series of pyridyl-arylmethane. 

PMID- 24308857
TI  - Soybean peroxidase-mediated degradation of an azo dye- a detailed mechanistic
      study.
AB  - BACKGROUND: Peroxidases are emerging as an important class of enzymes that can be
      used for the efficient degradation of organic pollutants. However, detailed
      studies identifying the various intermediates produced and the mechanisms
      involved in the enzyme-mediated pollutant degradation are not widely published.
      RESULTS: In the present study, the enzymatic degradation of an azo dye (Crystal
      Ponceau 6R, CP6R) was studied using commercially available soybean peroxidase
      (SBP) enzyme. Several operational parameters affecting the enzymatic degradation
      of dye were evaluated and optimized, such as initial dye concentration, H2O2
      dosage, mediator amount and pH of the solution. Under optimized conditions, 40
      ppm dye solution could be completely degraded in under one minute by SBP in the
      presence of H2O2 and a redox mediator. Dye degradation was also confirmed using
      HPLC and TOC analyses, which showed that most of the dye was being mineralized to
      CO2 in the process. CONCLUSIONS: Detailed analysis of metabolites, based on LC/MS
      results, showed that the enzyme-based degradation of the CP6R dye proceeded in
      two different reaction pathways- via symmetric azo bond cleavage as well as
      asymmetric azo bond breakage in the dye molecule. In addition, various critical
      transformative and oxidative steps such as deamination, desulfonation, keto
      oxidation are explained on an electronic level. Furthermore, LC/MS/MS analyses
      confirmed that the end products in both pathways were small chain aliphatic
      carboxylic acids.

PMID- 24308859
TI  - Successful treatment of macular retinoblastoma with superselective ophthalmic
      artery infusion of melphalan.
AB  - PURPOSE: To report our experience with superselective ophthalmic artery infusion
      of melphalan (SOAIM) for macular retinoblastoma to obtain tumor control while
      preserving as much useful vision as possible. METHODS: Five patients with newly
      diagnosed unilateral retinoblastoma involving the macula were selected within a
      group of patients eligible for SOAIM as the primary treatment. RESULTS: The mean
      tumor basal dimension and thickness in this group of five patients with macular
      retinoblastoma were 11.6 and 12.3 mm, respectively. The stage at diagnosis ranged
      from II to VB (Reese-Ellsworth) or B to D (International Classification System).
      Tumor regression with SOAIM was achieved in all cases with regression patterns
      type I in four cases and III in one case. CONCLUSIONS: SOAIM can be of value in
      the treatment of macular retinoblastoma. It may allow the salvage of the residual
      eyesight with a low rate of complications due to the local and systemic toxicity
      related to chemotherapy.

PMID- 24308860
TI  - Rescaling the trophic structure of marine food webs.
AB  - Measures of trophic position (TP) are critical for understanding food web
      interactions and human-mediated ecosystem disturbance. Nitrogen stable isotopes
      (delta(15) N) provide a powerful tool to estimate TP but are limited by a
      pragmatic assumption that isotope discrimination is constant (change in delta(15)
      N between predator and prey, Delta(15) N = 3.40/00), resulting in an additive
      framework that omits known Delta(15) N variation. Through meta-analysis, we
      determine narrowing discrimination from an empirical linear relationship between
      experimental Delta(15) N and delta(15) N values of prey consumed. The resulting
      scaled Delta(15) N framework estimated reliable TPs of zooplanktivores to
      tertiary piscivores congruent with known feeding relationships that radically
      alters the conventional structure of marine food webs. Apex predator TP estimates
      were markedly higher than currently assumed by whole-ecosystem models, indicating
      perceived food webs have been truncated and species-interactions over simplified.
      The scaled Delta(15) N framework will greatly improve the accuracy of trophic
      estimates widely used in ecosystem-based management.

PMID- 24308862
TI  - The combined effect of dissolved organic carbon and salinity on the
      bioaccumulation of copper in marine mussel larvae.
AB  - Larvae of Mytilus spp. are among the most Cu sensitive marine species. In this
      study we assessed the combined effect of salinity and dissolved organic carbon
      (DOC) on Cu accumulation on mussel larvae. Larvae were exposed for 48 h to three
      Cu concentrations in each of nine salinity/DOC treatments. Synchrotron radiation
      X-ray fluorescence was used to determine the Cu concentration in 36 individual
      larvae with a spatial resolution of 10 * 10 MUm. Cu body burden concentrations
      varied between 1.1 and 27.6 MUg/g DW larvae across all treatments and Cu was
      homogeneously distributed at this spatial resolution level. Our results indicate
      decreasing Cu accumulation with increasing DOC concentrations which can be
      explained by an increase in Cu complexation. In contrast, salinity had a
      nonlinear effect on Cu. This cannot be explained by copper speciation or
      competition processes and suggests a salinity-induced alteration in physiology. 

PMID- 24308863
TI  - Menopause negatively impacts sexual lives of middle-aged Iranian women: a cross
      sectional study.
AB  - The study aimed to explore associations between sexual function, demographic
      variables, health and menopausal status among middle-aged Iranian women.
      Participants were 200 Iranian middle-aged women (40-65 years). All women
      completed the Female Sexual Function Index and the Brief Profile of Female Sexual
      Function. Data were analyzed using a Pearson correlation statistical test, a one
      way analysis of variance, an independent t test, and a linear regression
      analysis. Advanced age, lower education, and socioeconomic status were
      significantly correlated with the lower scores on the Female Sexual Function
      Index. Lower scores on the Female Sexual Function Index were associated with
      being retired; having a hysterectomy or oophorectomy; and presence of hot
      flashes, vaginal dryness, health problems, prescription drug use, and cold
      sweats. There were no significant associations between middle-aged women's sexual
      function and ethnicity, body mass index, alcohol consumption, severity of hot
      flashes, and hot flash frequency. Sexual desire was decreased or absent in 94.5%
      of the postmenopausal respondents. Our findings appear that sexual function is
      associated with sociodemographic characteristics of Iranian middle-aged women.
      Gender-sensitive counseling and medical services for aging Iranian women can
      improve the quality of women's sexual lives. 

PMID- 24308861
TI  - Anti-inflammatory effects of cannabinoid CB(2) receptor activation in endotoxin
      induced uveitis.
AB  - BACKGROUND AND PURPOSE: Cannabinoid CB2 receptors mediate immunomodulation. Here,
      we investigated the effects of CB2 receptor ligands on leukocyte-endothelial
      adhesion and inflammatory mediator release in experimental endotoxin-induced
      uveitis (EIU). EXPERIMENTAL APPROACH: EIU was induced by intraocular injection of
      lipopolysaccharide (LPS, 20 ng.MUL(-1) ). Effects of the CB2 receptor agonist,
      HU308 (1.5% topical), the CB2 receptor antagonist, AM630 (2.5 mg.kg(-1) i.v.), or
      a combination of both compounds on leukocyte-endothelial interactions were
      measured hourly for 6 h in rat iridial vasculature using intravital microscopy.
      Anti-inflammatory actions of HU308 were compared with those of clinical
      treatments for uveitis - dexamethasone, prednisolone and nepafenac. Transcription
      factors (NF-kappaB, AP-1) and inflammatory mediators (cytokines, chemokines and
      adhesion molecules) were measured in iris and ciliary body tissue. KEY RESULTS:
      Leukocyte-endothelium adherence was increased in iridial microvasculature between
      4-6 h after LPS. HU308 reduced this effect after LPS injection and decreased pro
      inflammatory mediators: TNF-alpha, IL-1beta, IL-6, CCL5 and CXCL2. AM630 blocked
      the actions of HU-308, and increased leukocyte-endothelium adhesion. HU-308
      decreased levels of the transcription factors NF-kappaB and AP-1, while AM630
      increased levels of NF-kappaB. Topical treatments with dexamethasone,
      prednisolone or nepafenac, failed to alter leukocyte adhesion or mitigate LPS
      induced increases in inflammatory mediators during the 6 h of EIU. CONCLUSION AND
      IMPLICATIONS: Activation of CB2 receptors was anti-inflammatory in a model of
      acute EIU and involved a reduction in NF-kappaB, AP-1 and inflammatory mediators.
      CB2 receptors may be promising drug targets for the development of novel ocular
      anti-inflammatory agents. LINKED ARTICLES: This article is part of a themed
      section on Cannabinoids 2013. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-6.

PMID- 24308864
TI  - Quality of life of patients with euthymic bipolar disorder and its associations
      with demographic and clinical characteristics, psychopathology, and cognitive
      deficits.
AB  - PURPOSE: Little is known about quality of life (QOL) in Chinese patients with
      bipolar disorder (BD) in remission (euthymia). This study examined the QOL of
      such a cohort of BD patients and its demographic, clinical, and cognitive
      correlates. DESIGN AND METHODS: Forty-seven euthymic BD patients and 47 matched
      healthy controls formed the study sample. Socio-demographic characteristics,
      prospective memory, retrospective memory, intelligence quotient, and executive
      functioning were measured in all participants together with patients'
      psychopathology ratings. FINDINGS: Multivariate analyses revealed that compared
      to controls, euthymic BD patients had significantly lower satisfaction with
      physical QOL domain. Only subthreshold depressive symptoms independently
      contributed to reduced satisfaction with physical and environmental QOL domains,
      whereas no variable predicted its psychological and social domains. PRACTICE
      IMPLICATIONS: Contrary to findings from Western settings, demographic variables
      and cognitive deficits had no associations with any QOL domain in euthymic
      Chinese BD patients. Control of subthreshold depressive symptoms in euthymic BD
      patients might enhance their QOL.

PMID- 24308865
TI  - Activation of caspase-9 and its influencing factors in beef during conditioning.
AB  - To study the activation of caspase-9 and its potential influence in conditioning,
      longissimus thoracis (LT), semitendinosus (STN) and psoas minor (PMi) muscles
      were used to analyze the ratio of pro-apoptotic bax to anti-apoptotic bcl-2 in
      fresh tissues and observe the changes in ATP, cytosolic cytochrome c and caspase
      9 activity levels during storage at 4 degrees C. Caspase-9 activity at 5 h is
      higher than the activity at 0 and 24 h in the muscles (P<0.001). The ATP content
      decreased between 0 and 3 h, between 8 and 14 h in the PMi and LT muscles
      (P<0.0001), whereas between 0 and 5 h, between 8 and 14 h in the STN muscle
      (P<0.0001). There is 60.2%, 55.3% and 43.1% available ATP in the STN, LT and PMi
      muscles at 5 h, respectively. The cytosolic cytochrome c level increased during 5
      and 24 h storage in the LT and PMi muscles (P<0.0001), during 5 and 96 h in the
      STN muscle (P<0.0001). The cytosolic cytochrome c at 24 h (P<0.001) and ratio of
      bax to bcl-2 (P<0.05) was higher in the PMi than in other muscles. We concluded
      that the increase in cytosolic cytochrome c and available intracellular ATP
      should be responsible for the increase in caspase-9 activity; the activation of
      caspase-9 could be limited by the subsequent depletion of ATP; the postmortem
      release level of cytochrome c could be determined by the ratio of bax to bcl-2 in
      fresh tissues.

PMID- 24308866
TI  - Sodium ion interactions with aqueous glucose: insights from quantum mechanics,
      molecular dynamics, and experiment.
AB  - In the last several decades, significant efforts have been conducted to
      understand the fundamental reactivity of glucose derived from plant biomass in
      various chemical environments for conversion to renewable fuels and chemicals.
      For reactions of glucose in water, it is known that inorganic salts naturally
      present in biomass alter the product distribution in various deconstruction
      processes. However, the molecular-level interactions of alkali metal ions and
      glucose are unknown. These interactions are of physiological interest as well,
      for example, as they relate to cation-glucose cotransport. Here, we employ
      quantum mechanics (QM) to understand the interaction of a prevalent alkali metal,
      sodium, with glucose from a structural and thermodynamic perspective. The effect
      on beta-glucose is subtle: a sodium ion perturbs bond lengths and atomic partial
      charges less than rotating a hydroxymethyl group. In contrast, the presence of a
      sodium ion significantly perturbs the partial charges of alpha-glucose anomeric
      and ring oxygens. Molecular dynamics (MD) simulations provide dynamic sampling in
      explicit water, and both the QM and the MD results show that sodium ions
      associate at many positions with respect to glucose with reasonably equivalent
      propensity. This promiscuous binding nature of Na(+) suggests that computational
      studies of glucose reactions in the presence of inorganic salts need to ensure
      thorough sampling of the cation positions, in addition to sampling glucose
      rotamers. The effect of NaCl on the relative populations of the anomers is
      experimentally quantified with light polarimetry. These results support the
      computational findings that Na(+) interacts similarly with alpha- and beta
      glucose. 

PMID- 24308867
TI  - Palladium-catalyzed coupling of alkynes with unactivated alkenes in ionic
      liquids: a regio- and stereoselective synthesis of functionalized 1,6-dienes and
      their analogues.
AB  - A palladium-catalyzed regio- and stereoselective intermolecular tandem reaction
      of alkynes and unactivated 1,6-enols in ionic liquids is described, providing a
      practical, efficient, and versatile method for the synthesis of functionalized
      1,6-dienes in moderate to good yields. The present reaction has high functional
      group tolerance and gives products on a gram scale. Mechanistic studies indicate
      that the reaction might proceed via a chain-walking mechanism. 

PMID- 24308869
TI  - Very late recovery of dapsone-induced methemoglobinemia.

PMID- 24308868
TI  - Intervention versus standard medical treatment in patients with symptomatic
      occlusion of the internal carotid artery: a randomised oxygen-15 PET study.
AB  - BACKGROUND: The aim of this randomised pilot study was to investigate the
      haemodynamic effects measured by oxygen-15 positron emission tomography (PET) of
      interventional treatment consisting of either endarterectomy or endovascular
      treatment of stenosed cerebropetal arteries, or tapering of antihypertensive
      medication in comparison with standard medical treatment alone in patients with
      symptomatic internal carotid artery (ICA) occlusion. METHODS: Twenty-three
      patients with symptomatic ICA occlusion underwent PET scanning at baseline and
      after 3 months. Twelve patients were randomised to intervention (either
      endarterectomy or endovascular treatment of stenosed cerebropetal arteries, or
      tapering of antihypertensive medication) and 11 to standard medical treatment
      alone. Primary outcome was a change in cerebral blood flow (CBF), cerebral blood
      volume (CBV) and/or oxygen extraction fraction (OEF) after 3 months measured by
      PET. RESULTS: There were no differences in changes in CBF, CBV or OEF between the
      two groups. Only patients with compromised perfusion at presentation showed a
      borderline significant increase in CBF of 2.8 mL/min/100 mL (95% confidence
      interval 0.0 to 5.7) after intervention (n = 7). CONCLUSION: This pilot study
      shows that in patients with symptomatic ICA occlusion, oxygen-15 PET did not
      detect differences in improvement of CBF, CBV or OEF between interventional and
      standard treatment.

PMID- 24308870
TI  - Immune selection of tumor cells in TCR beta-chain transgenic mice.
AB  - The concept of immunological surveillance implies that immunogenic variants of
      tumor cells arising in the organism can be recognized by the immune system. Tumor
      progression is provided by somatic evolution of tumor cells under the pressure of
      the immune system. The loss of MHC Class I molecules on the surface of tumor
      cells is one of the most known outcomes of immune selection. This study developed
      a model of immune selection based on the immune response of TCR 1d1 single beta
      chain transgenic B10.D2(R101) (K(d)I(d)D(b)) mice to allogeneic EL4 (H-2(b))
      thymoma cells. In wild-type B10.D2(R101) mice, immunization with EL4 cells
      induced a vigorous CTL response targeted to the H-2K(b) molecule and results in
      full rejection of the tumor cells. In contrast, transgenic mice developed a
      compromised proliferative response in mixed-lymphocyte response assays and were
      unable to reject transplanted allogeneic EL4 cells. During the immune response to
      EL4 cells, CD8(+) T-lymphocytes with endogenous beta-chains accumulated
      predominantly in the spleen of transgenic mice and only a small part of the T
      lymphocytes expressing transgenic beta-chains became CD8(+)CD44(+)CD62L(-)
      effectors. Then, instead of a full elimination of tumor cells as in wild-type
      mice, a reproducible prolonged equilibrium phase and subsequent escape was
      observed in transgenic mice that resulted in death of 90% of the mice in 40-60
      days after grafting. Prolonged exposure of tumor cells to the pressure of the
      immune system in transgenic mice in vivo resulted in a stable loss of H-2K(b)
      molecules on the EL4 cell surface. Genetic manipulation of the T-lymphocyte
      repertoire was sufficient to reproduce the classic pattern of interactions
      between tumor cells and the immune system, usually observed in reliable syngeneic
      models of anti-tumor immunity. This newly-developed model could be used in
      further studies of immunoregulatory circuits common for transplantational and
      anti-tumor immune responses.

PMID- 24308871
TI  - Lactose intolerance in irritable bowel syndrome patients with diarrhoea: the
      roles of anxiety, activation of the innate mucosal immune system and visceral
      sensitivity.
AB  - BACKGROUND: Irritable bowel syndrome patients with diarrhoea (IBS-D) often report
      intolerance to milk; however, the mechanism underlying these symptoms is unknown.
      AIM: To assess the role of psychological factors, immune activation and visceral
      sensitivity on the development of lactose intolerance (LI) in IBS-D patients.
      METHODS: Fifty-five IBS-D patients and 18 healthy controls (HCs) with lactase
      deficiency underwent a 20-g lactose hydrogen breath test (LHBT). Patients were
      categorised as lactose malabsorption (LM; malabsorption only) or LI
      [malabsorption plus increase in total symptom score (TSS). Measurements included
      (i) psychological status; (ii) enteric biopsies with quantification of mast cells
      (MCs), T-lymphocytes and enterochromaffin cells; (iii) serum cytokines; (iv)
      rectal sensitivity before and after lactose ingestion. RESULTS: LI was more
      prevalent in IBS-D patients than HCs [25/55 (46%) vs. 3/18 (17%), P = 0.029]. IBS
      D patients with LI had (i) higher levels of anxiety than those with LM (P =
      0.017) or HCs (P = 0.006); (ii) increased mucosal MCs compared with LM (P =
      0.006) and HCs (P < 0.001); (iii) raised serum TNF-alpha compared with LM (P =
      0.034) and HCs (P < 0.001) and (iv) increased rectal sensitivity after lactose
      ingestion compared with LM (P < 0.001) or HCs (P < 0.001). Severity of abdominal
      symptoms after lactose ingestion was associated with the increase in visceral
      sensitivity after lactose intake (r = 0.629, P < 0.001), MCs (r = 0.650, P <
      0.001) and anxiety (r = 0.519, P < 0.001). CONCLUSIONS: IBS-D patients with
      lactose intolerence are characterised by anxiety, mucosal immune activation and
      increased visceral sensitivity after lactose ingestion. The presence of these
      biomarkers may indicate an IBS phenotype that responds to dietary therapy and/or
      mast cell stabilisers.

PMID- 24308872
TI  - Characterization of Aspergillus nidulans alpha-glucan synthesis: roles for two
      synthases and two amylases.
AB  - Cell walls are essential for fungal survival and growth. Fungal walls are ~ 90%
      carbohydrate, mostly types not found in humans, making them promising targets for
      anti-fungal drug development. Echinocandins, which inhibit the essential beta
      glucan synthase, are already clinically available. In contrast, alpha-glucan,
      another abundant fungal cell wall component has attracted relatively little
      research attention because it is not essential for most fungi. Aspergillus
      nidulans has two alpha-glucan synthases (AgsA and AgsB) and two alpha-amylases
      (AmyD and AmyG), all of which affect alpha-glucan synthesis. Gene deletion showed
      that AgsB was the major synthase. In addition, AmyG promoted alpha-glucan
      synthesis whereas AmyD had a repressive effect. The lack of alpha-glucan had no
      phenotypic impact on solid medium, but reduced conidial adhesion during
      germination in shaken liquid. Moreover, alpha-glucan level correlated with
      resistance to Calcofluor White. Intriguingly, overexpression of agsA could
      compensate for the loss of agsB at the alpha-glucan level, but not for phenotypic
      defects. Thus, products of AgsA and AgsB have different roles in the cell wall,
      consistent with agsA being mainly expressed at conidiation. These results suggest
      that alpha-glucan contributes to drug sensitivity and conidia adhesion in A.
      nidulans, and is differentially regulated by two synthases and two amylases.

PMID- 24308873
TI  - Should diagnosis codes from emergency department data be used for case selection
      for emergency department key performance indicators?
AB  - OBJECTIVE: The aim of the present study was to assess the suitability of
      emergency department (ED) discharge diagnosis for identifying patient cohorts
      included in the definitions of key performance indicators (KPIs) that are used to
      evaluate ED performance. METHODS: Hospital inpatient episodes of care with a
      principal diagnosis that corresponded to an ED-defined KPI were extracted from
      the Queensland Hospital Admitted Patient Data Collection (QHAPDC) for the year
      2010-2011. The data were then linked to the corresponding ED patient record and
      the diagnoses applied in the two settings were compared. RESULTS: The asthma and
      injury cohorts produced favourable results with respect to matching the QHAPDC
      principal diagnosis with the ED discharge diagnosis. The results were generally
      modest when the QHAPDC principal diagnosis was upper respiratory tract infection,
      poisoning and toxic effects or a mental health diagnosis, and were quite poor for
      influenza. CONCLUSIONS: There is substantial variation in the capture of patient
      cohorts using discharge diagnosis as recorded on Queensland Hospital Emergency
      Department data. WHAT IS KNOWN ABOUT THE TOPIC? There are several existing KPIs
      that are defined according to the diagnosis recorded on ED data collections.
      However, there have been concerns over the quality of ED diagnosis in Queensland
      and other jurisdictions, and the value of these data in identifying patient
      cohorts for the purpose of assessing ED performance remains uncertain. WHAT DOES
      THIS PAPER ADD? This paper identifies diagnosis codes that are suitable for use
      in capturing the patient cohorts that are used to evaluate ED performance, as
      well as those codes that may be of limited value. WHAT ARE THE IMPLICATIONS FOR
      PRACTITIONERS? The limitations of diagnosis codes within ED data should be
      understood by those seeking to use these data items for healthcare planning and
      management or for research into healthcare quality and outcomes.

PMID- 24308875
TI  - Changes in order parameters associated with ceramide-mediated membrane
      reorganization measured using pTIRFM.
AB  - The enzymatic generation of ceramide has significant effects on the biophysical
      properties of lipid bilayers and can lead to the extensive reorganization of cell
      membranes. We have synthesized and characterized a headgroup-labeled fluorescent
      lipid probe (NBD-ceramide, NBD-Cer) and demonstrated that it can be used for
      polarized total internal reflection fluorescence microscopy experiments to probe
      changes in membrane order that result from ceramide incorporation. NBD-Cer
      measures significantly higher order parameters for the liquid-ordered (Lo)
      domains ([P2] = 0.40 +/- 0.03) than for the liquid-disordered phase (Ld, fluid,
      [P2] = 0.22 +/- 0.02) of phase-separated bilayers prepared from egg
      sphingomyelin, dioleolyphosphatidylcholine, and cholesterol mixtures. The probe
      also responds to changes in packing induced by the direct incorporation of
      ceramide or the variation in the ionic strength of the aqueous medium. Order
      parameter maps obtained after enzyme treatment of bilayers with coexisting Lo and
      Ld phases show two distinct types of behavior. In regions of high enzyme
      activity, the initial Lo/Ld domains are replaced by large, dark features that
      have high membrane order corroborating previous hypotheses that these are
      ceramide-enriched regions of the membrane. In areas of low enzyme activity, the
      size and shape of the Lo domains are conserved, but there is an increase in the
      order parameter for the initial Ld phase ([P2] = 0.30 +/- 0.01). This is
      attributed to the incorporation of ceramide in the Lo domains with the
      concomitant expulsion of cholesterol into the surrounding fluid phase, increasing
      its order parameter.

PMID- 24308874
TI  - Evidence-based new service package vs. routine service package for smoking
      cessation to prevent high risk patients from cardiovascular diseases (CVD): study
      protocol for randomized controlled trial.
AB  - BACKGROUND: Smoking cessation is a high-priority intervention to prevent CVD
      events and deaths in developing countries. While several interventions to stop
      smoking have been proved successful, the question of how to increase their
      effectiveness and practicality in developing countries remains. In this study, a
      newly devised evidence-based smoking cessation service package will be compared
      with the existing service in a randomized controlled trial within the community
      setting of Thailand. METHOD/DESIGN: This randomized control trial will recruit
      440 current smokers at CVD risk because of being diabetic and/or hypertensive.
      Informed, consented participants will be randomly allocated into the new service
      package arm and the routine service arm. The study will take place in the non
      communicable disease clinics of the Maetha District Hospital, Lampang, northern
      Thailand. The new smoking-cessation service-package comprises (1) regular patient
      motivation and coaching from the same primary care nurse over a 3-month period;
      (2) monthly application of piCO + smokerlyzer to sustain motivation of smoker's
      quitting attempt and provide positive feedback over a 3-month period; (3)
      assistance by an assigned family member; (4) nicotine replacement chewing gum to
      relieve withdrawal symptoms. This new service will be compared with the
      traditional routine service comprising the 5A approach in a 1-year follow-up.
      Participants who consent to participate in the study but refuse to attempt
      quitting smoking will be allocated to the non-randomized arm, where they will be
      just followed up and monitored. Primary outcome of the study is smoking cessation
      rate at 1-year follow-up proven by breath analysis measuring carbomonoxide in
      parts per million in expired air. Secondary outcomes are smoking cessation rate
      at the 6-month follow-up, blood pressure and heart rate, CVD risk according to
      the Framingham general cardiovascular risk score, CVD events and deaths at the 12
      month follow-up, and the cost-effectiveness of the health service packages.
      Intention-to-treat analysis will be followed. Factors influencing smoking
      cessation will be analyzed by the structure equation model. DISCUSSION: This
      multicomponent intervention, accessible at primary healthcare clinics, and
      focusing on the individual as well as the family and social environment, is
      unique and expected to work effectively. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN89315117.

PMID- 24308876
TI  - Metered dose inhaler technique among inner-city asthmatics and its association
      with asthma medication adherence.
AB  - INTRODUCTION: Inhaled medications, critical for asthma treatment, are self
      administered through metered dose inhalers (MDI). Asthma self-management hinges
      on adherence to these medications and to proper MDI technique. OBJECTIVE: To
      assess predictors of proper MDI technique, and MDI technique as a tool to
      identify patients with low adherence to inhaled medications. METHODS: Prospective
      cohort of asthmatics from clinics in New York, NY and New Brunswick, NJ. MDI
      technique was assessed using a standardized checklist. Adherence to inhaled
      asthma controller medication was evaluated with the Medication Adherence Report
      Scale. Predictors of MDI technique were evaluated using regression analyses. The
      distribution of number of MDI technique steps missed was compared in adherent vs.
      non-adherent asthmatics. RESULTS: Overall, 326 patients were included (55%
      Hispanic, 27% Black). In adjusted analyses, age < 55 years was significantly
      associated with MDI technique (P = 0.03). Overall, 12%, 34%, 40% of asthmatics
      missed 5-6, 3-4, or 1-2 MDI steps; 16% received a perfect MDI technique score.
      Adherence rates were 20%, 39%, 48%, and 62% among those who missed 5-6, 3-4, 1-2,
      or none of the steps in the MDI technique checklist (P < 0.001). CONCLUSION: Poor
      MDI technique is common among inner-city patients with asthma and is associated
      with poor adherence to controller medications. Older patients with asthma are at
      higher risk of improper MDI technique. Assessment of MDI technique may be a
      simple clinical aid to identify patients with low adherence to controller
      medications.

PMID- 24308877
TI  - Introduction. Standard market mechanisms than does traditional Medicare.

PMID- 24308878
TI  - Integrating risk adjustment and enrollee premiums in health plan payment.
AB  - In two important health policy contexts - private plans in Medicare and the new
      state-run "Exchanges" created as part of the Affordable Care Act (ACA) - plan
      payments come from two sources: risk-adjusted payments from a Regulator and
      premiums charged to individual enrollees. This paper derives principles for
      integrating risk-adjusted payments and premium policy in individual health
      insurance markets based on fitting total plan payments to health plan costs per
      person as closely as possible. A least squares regression including both health
      status and variables used in premiums reveals the weights a Regulator should put
      on risk adjusters when markets determine premiums. We apply the methods to an
      Exchange-eligible population drawn from the Medical Expenditure Panel Survey
      (MEPS). 

PMID- 24308879
TI  - Do Medicare Advantage plans select enrollees in higher margin clinical
      categories?
AB  - The CMS-HCC risk adjustment system for Medicare Advantage (MA) plans calculates
      weights, which are effectively relative prices, for beneficiaries with different
      observable characteristics. To do so it uses the relative amounts spent per
      beneficiary with those characteristics in Traditional Medicare (TM). For multiple
      reasons one might expect relative amounts in MA to differ from TM, thereby making
      some beneficiaries more profitable to treat than others. Much of the difference
      comes from differences in how TM and MA treat different diseases or diagnoses.
      Using data on actual medical spending from two MA-HMO plans, we show that the
      weights calculated from MA costs do indeed differ from those calculated using TM
      spending. One of the two plans (Plan 1) is more typical of MA-HMO plans in that
      it contracts with independent community providers, while the other (Plan 2) is
      vertically integrated with care delivery. We calculate margins, or average
      revenue/average cost, for Medicare beneficiaries in the two plans who have one of
      48 different combinations of medical conditions. The two plans' margins for these
      48 conditions are correlated (r=0.39, p<0.01). Both plans have margins that are
      more positive for persons with conditions that are managed by primary care
      physicians and where medical management can be effective. Conversely they have
      lower margins for persons with conditions that tend to be treated by specialists
      with greater market power than primary care physicians and for acute conditions
      where little medical management is possible. The two plan's margins among
      beneficiaries with different observable characteristics vary over a range of 160
      and 98 percentage points, respectively, and thus would appear to offer
      substantial incentive for selection by HCC. Nonetheless, we find no evidence of
      overrepresentation of beneficiaries in high margin HCC's in either plan. Nor,
      using the margins from Plan 1, the more typical plan, do we find evidence of
      overrepresentation of high margin HCC's in Medicare more generally. These results
      do not permit a conclusion on overall social efficiency, but we note that
      selection according to margin could be socially efficient. In addition, our
      findings suggest there are omitted interaction terms in the risk adjustment model
      that Medicare currently uses. 

PMID- 24308880
TI  - The spillover effects of Medicare managed care: Medicare Advantage and hospital
      utilization.
AB  - More than a quarter of Medicare beneficiaries are enrolled in Medicare Advantage,
      which was created in large part to improve the efficiency of health care delivery
      by promoting competition among private managed care plans. This paper explores
      the spillover effects of the Medicare Advantage program on the traditional
      Medicare program and other patients, taking advantage of changes in Medicare
      Advantage payment policy to isolate exogenous increases in Medicare Advantage
      enrollment and trace out the effects of greater managed care penetration on
      hospital utilization and spending throughout the health care system. We find that
      when more seniors enroll in Medicare managed care, hospital costs decline for all
      seniors and for commercially insured younger populations. Greater managed care
      penetration is not associated with fewer hospitalizations, but is associated with
      lower costs and shorter stays per hospitalization. These spillovers are
      substantial - offsetting more than 10% of increased payments to Medicare
      Advantage plans. 

PMID- 24308881
TI  - Competitive bidding in Medicare Advantage: effect of benchmark changes on plan
      bids.
AB  - Bidding has been proposed to replace or complement the administered prices that
      Medicare pays to hospitals and health plans. In 2006, the Medicare Advantage
      program implemented a competitive bidding system to determine plan payments. In
      perfectly competitive models, plans bid their costs and thus bids are insensitive
      to the benchmark. Under many other models of competition, bids respond to changes
      in the benchmark. We conceptualize the bidding system and use an instrumental
      variable approach to study the effect of benchmark changes on bids. We use 2006
      2010 plan payment data from the Centers for Medicare and Medicaid Services,
      published county benchmarks, actual realized fee-for-service costs, and Medicare
      Advantage enrollment. We find that a $1 increase in the benchmark leads to about
      a $0.53 increase in bids, suggesting that plans in the Medicare Advantage market
      have meaningful market power. 

PMID- 24308883
TI  - Digesting the doughnut hole.
AB  - Despite its success, Medicare Part D has been widely criticized for the gap in
      coverage, the so-called "doughnut hole". We compare the use of prescription drugs
      among beneficiaries subject to the coverage gap with usage among beneficiaries
      who are not exposed to it. We find that the coverage gap does, indeed, disrupt
      the use of prescription drugs among seniors with diabetes. But the declines in
      usage are modest and concentrated among higher cost, brand-name medications.
      Demand for high cost medications such as antipsychotics, antiasthmatics, and
      drugs of the central nervous system decline by 8-18% in the coverage gap, while
      use of lower cost medications with high generic penetration such as beta
      blockers, ACE inhibitors and antidepressants decline by 3-5% after reaching the
      gap. More importantly, lower adherence to medications is not associated with
      increases in medical service use. 

PMID- 24308882
TI  - Plan selection in Medicare Part D: evidence from administrative data.
AB  - We study the Medicare Part D prescription drug insurance program as a bellwether
      for designs of private, non-mandatory health insurance markets, focusing on the
      ability of consumers to evaluate and optimize their choices of plans. Our
      analysis of administrative data on medical claims in Medicare Part D suggests
      that fewer than 25% of individuals enroll in plans that are ex ante as good as
      the least cost plan specified by the Plan Finder tool made available to seniors
      by the Medicare administration, and that consumers on average have expected
      excess spending of about $300 per year, or about 15% of expected total out-of
      pocket cost for drugs and Part D insurance. These numbers are hard to reconcile
      with decision costs alone; it appears that unless a sizeable fraction of
      consumers place large values on plan features other than cost, they are not
      optimizing effectively. 

PMID- 24308884
TI  - Pharmaceutical advertising and Medicare Part D.
AB  - We explore how and to what extent prescription drug insurance expansions affect
      incentives for pharmaceutical advertising. When insurance expansions make markets
      more profitable, firms respond by boosting advertising. Theory suggests this
      effect will be magnified in the least competitive drug classes, where firms
      internalize a larger share of the benefits from advertising. Empirically, we find
      that the implementation of Part D coincides with a 14-19% increase in total
      advertising expenditures. This effect is indeed concentrated in the least
      competitive drug classes. The additional advertising raised utilization among non
      elderly patients outside the Part D program by about 3.6%. This is roughly half
      of the direct utilization effect of Part D on elderly beneficiaries. The results
      suggest the presence of considerable spillover effects from publicly subsidized
      prescription drug insurance on the utilization and welfare of consumers outside
      the program. 

PMID- 24308886
TI  - Benefits of the ballot box for species conservation.
AB  - Recent estimates reaffirm that conservation funds are insufficient to meet
      biodiversity conservation goals. Organisations focused on biodiversity
      conservation therefore need to capitalise on investments that societies make in
      environmental protection that provide ancillary benefits to biodiversity. Here,
      we undertake the first assessment of the potential ancillary benefits from the
      ballot box in the United States, where citizens vote on referenda to conserve
      lands for reasons that may not include biodiversity directly but that indirectly
      might enhance biodiversity conservation. Our results suggest that referenda occur
      in counties with significantly greater biodiversity than counties chosen at
      random. We also demonstrate that large potential gains for conservation are
      possible if the past and likely future outcomes of these ballot box measures are
      directly incorporated into national-scale conservation planning efforts. The
      possible synergies between ballot box measures and other biodiversity
      conservation efforts offer an under-utilised resource for supporting
      conservation. 

PMID- 24308887
TI  - Synergistic effect of LEP and LEPR gene polymorphism on body mass index in a
      Chinese population.
AB  - Both leptin (LEP) and leptin receptor (LEPR) are important in the regulation of
      body weight. In this study, we evaluated the individual and combined effects of a
      polymorphic microsatellite marker in the LEP gene 3' flanking region and two
      polymorphisms (Lys109Arg and Lys656Asn) of the LEPR gene on metabolic markers for
      obesity in a Chinese population. The genotypes of polymorphisms in LEP and LEPR
      gene were determined by PCR and SSCP assay in 230 simple obese subjects and 202
      control subjects of Chinese population. Logistic regression analysis showed that
      polymorphism in LEP gene 3' flanking region was associated with waist/hip ratio
      (WHR) (P = 0.042). Individually, Lys109Arg variant in LEPR gene was associated
      with systolic blood pressure (P = 0.031) in males, and Lys656Asn variant was
      associated with serum triglyceride level (P = 0.026). Interestingly, only
      subjects that simultaneously exhibit all three polymorphisms showed a
      significantly elevated BMI (29.30 +/- 0.85 vs 26.91 +/- 1.19, P = 0.037). Taken
      together, our data suggest that a combination of polymorphism in the LEP gene 3'
      flanking region, and Lys109Arg, Lys656Asn variants in LEPR gene is associated
      with obesity in Chinese Han population.

PMID- 24308888
TI  - Age differences in the risk of diabetes incidence according to body mass index
      level in Japanese women.
AB  - OBJECTIVE: To investigate the age differences in the risk of diabetes incidence
      according to body mass index (BMI). METHODS: For an average of 10.3 years, this
      study prospectively followed a cohort of 4725 women aged 30-69 years without
      diabetes at a baseline health check-up conducted between April 1990 and March
      1992. Diabetes onset was identified by fasting and random plasma glucose level,
      HbA1c or the medical treatment for diabetes by questionnaire. We stratified the
      subjects according to age (30-39, 40-49, 50-59 and 60-69 years), and calculated
      the risk of diabetes incidence according to BMI categories (<18.5, 18.5-22.9,
      23.0-24.9 and >=25.0 kg/m(2)) using the Cox proportional hazards model. RESULTS:
      During 48,866 person-years of follow-up, 392 subjects developed diabetes. Using
      the normal group as the reference, the HR (95% CI) for diabetes incidence was
      elevated in obese women of all ages, ranging from a high of 4.72 (1.79-12.40) for
      women who were 30-39 years of age, to a low of 1.54 (1.02-2.33) for those who
      were 50-59 years of age. CONCLUSIONS: The risk of diabetes incidence according to
      BMI is different among different age groups of Japanese women. Obese is a strong
      risk factor for diabetes incidence among women of all ages, and especially among
      young adults.

PMID- 24308889
TI  - Measuring experiential avoidance in a bariatric surgery population--psychometric
      properties of AAQ-W.
AB  - BACKGROUND: Valid measures capturing underlying psychological processes post
      surgery for obesity are needed to help identify important clinical targets and
      develop psychosocial interventions in conjunction with surgery. The Acceptance
      and Action Questionnaire for Weight (AAQ-W) measures experiential avoidance and
      has never been evaluated in a bariatric surgery population. METHOD: Participants
      were recruited at a bariatric surgery clinic during follow-up care. The
      evaluation of psychometric properties of AAQ-W was done by repeated measurements
      of reliability (n = 62), convergent validity (n = 75 and n = 178), predictive
      validity (n = 61), factor analysis and calculation of internal consistency (n =
      178). RESULTS: The AAQ-W was found to have satisfactory psychometric properties.
      Internal consistency was high (alpha = .86). Results showed good stability over
      time (r = .77) and validity coefficients ranging from r = .36 to .71. AAQ-W
      scores measured six months post surgery predicted satisfaction with life,
      negative emotional states, emotional eating and general eating pathology measured
      one year post surgery. However AAQ-W measured at six months did not predict
      percent excess BMI Loss at one year. Factor analysis showed that a five factor
      solution (Food as Control, Body Acceptance, Self-Stigma, Self-Efficacy and
      Emotional Avoidance) might be a good fit (n = 178). CONCLUSION: This study shows
      that the AAQ-W appears to be a psychometrically sound measure that can be used by
      researchers and clinicians in the context of bariatric surgery.

PMID- 24308890
TI  - Prevention of childhood obesity: recruiting strategies via local paediatricians
      and study protocol for a telephone-based counselling programme.
AB  - AIM: Prevention research has to elucidate how families with overweight children
      can be convinced to participate in obesity intervention trials. Here we describe
      the detailed recruitment process for a telephone-based obesity prevention
      programme for families with overweight children and present participation rates,
      the study design and a socio-demographic description of participating families.
      METHODS: Overweight (BMI > 90th percentile) children and adolescents 4-17 years
      of age were screened via the German paediatrician network CrescNet. The
      prevention programme (multiple computer aided telephone counselling interviews)
      was suggested to eligible families via local paediatricians. Participating
      families were compared anthropometrically and socio-demographically to the entire
      screening population and to micro-census data, a representative national survey.
      RESULTS: The screening process assessed 4005 candidates for eligibility.
      Paediatricians reported having suggested programme participation to 3387
      candidates (referred to as 100%). 427 candidates (12.6%) returned a written
      consent for programme participation. 303 candidates (9.0%) started the
      intervention. The study population (n = 303) included more obese (45.6% vs.
      33.2%; p < 0.001) and fewer overweight participants (40.4% vs. 55.2%; p < 0.001)
      than the entire screening population. Compared to the micro-census, families with
      adolescents (8.2% vs. 16.9%; p < 0.001) and single parents (16.0% vs. 23.3%; p <
      0.005) were underrepresented in the study population, whereas families living in
      rural areas were overrepresented (58.7% vs. 50.2%; p < 0.005). CONCLUSIONS:
      Although 84.6% of the paediatricians forwarded the suggestion for programme
      participation to eligible families, participation rates for this low-threshold;
      telephone-based obesity intervention remained very low. "Hard-to-engage groups"
      for effective obesity prevention seem to include single parents, as well as
      parents of adolescents.

PMID- 24308891
TI  - Xanthine derivatives as activators of alpha-amylase: hypothesis on a link with
      the hyperglycemia induced by caffeine.
AB  - SUMMARY: Inhibitors of the mammalian alpha-amylases have been widely studied as
      medicines to be used in diabetes and obesity. However, there are few reports on
      activation of the enzyme, which could be detrimental in those conditions. Here,
      the effect of purine-derivated compounds has been studied on porcine pancreatic
      alpha-amylase. Methylxanthine-derivatives pentoxyfilline, theobromine and
      caffeine caused a 20-30% increase in enzyme activity in the presence of the
      natural substrate, starch. The activation effect was not dose-dependent, observed
      in the range of 10-200 MUM of the compounds, and hypothesized to be related with
      the hyperglycemia that is observed upon consuming caffeine.

PMID- 24308892
TI  - Predictors of remission of type 2 diabetes mellitus in obese patients after
      gastrointestinal surgery.
AB  - BACKGROUND: Gastroenterology is a beneficial treatment of morbidly obese type 2
      diabetes mellitus (T2DM). We aimed to identify the predictors for the treatment
      of T2DM obese patients. METHODS: A retrospective study consisting of 531 patients
      undergoing laparoscopic gastric banding (LGB), laparoscopic mini-gastric bypass
      (LMGB) and laparoscopic sleeve gastrectomy (LSG) from January 2004 to May 2007
      was performed. Patients with preoperative fasting serum glucose concentration of
      more than 126 mg/dl were diagnosed as T2DM. A postoperatively fasting serum
      glucose level of less than 110 mg/dl was considered to be remission of T2DM.
      RESULTS: Of the 531 patients, 62 (11.6%) were diagnosed as T2DM, including 23 men
      and 39 women, with a mean age of 31.8 +/- 9.2 years, and a mean body mass index
      (BMI) of 40.0 kg/m(2). The mean glucose at 3, 6, and 12 months after surgery were
      100.1 mg/dl, 95.1 mg/dl and 91.8 mg/dl, respectively. The mean body weight loss
      one year after surgery was 9.4% for LGB, 31.4% for LSG and 37.1% for LMGB,
      respectively. Among these operation methods (LGB, LMGB and LSG), the BMI, body
      weight, waist circumference, serum lipid profile and serum factors associated
      with glucose metabolism were significantly different during the one-year
      postoperative follow-up. Remission rate of T2DM was achieved in 84.8%, 58.8% and
      58.3% of patients for LMGB, LGB and LSG, respectively. The best operative method
      for the remission of T2DM was LMGB. Using an artificial neural network (ANN) data
      mining technique, waist circumference, operative methods and C-peptide were
      significantly predictors for the remission of T2 DM. CONCLUSION: One year after
      gastrointestinal surgery, improvement of serum lipid profiles and serum data
      related to glucose metabolism in the different operative methods were noticed.
      LMGB seems to be the most effective procedure for the reduction of serum glucose
      levels compared with LAGB and LSG.

PMID- 24308893
TI  - Heterologous regulation of agonist-independent MU-opioid receptor phosphorylation
      by protein kinase C.
AB  - BACKGROUND AND PURPOSE: Homologous agonist-induced phosphorylation of the MU
      opioid receptor (MOR) is initiated at the carboxyl-terminal S375, followed by
      phosphorylation of T370, T376 and T379. In HEK293 cells, this sequential and
      hierarchical multi-site phosphorylation is specifically mediated by G-protein
      coupled receptor kinases 2 and 3. In the present study, we provide evidence for a
      selective and dose-dependent phosphorylation of T370 after activation of PKC by
      phorbol esters. EXPERIMENTAL APPROACH: We used a combination of phospho site
      specific antibodies, kinase inhibitors and siRNA knockdown screening to identify
      kinases that mediate agonist-independent phosphorylation of the MOR in HEK293
      cells. In addition, we show with phospho site-specific antibodies were also used
      to study constitutive phosphorylation at S363 of MORs in mouse brain in vivo. KEY
      RESULTS: Activation of PKC by phorbol esters or heterologous activation of
      substance P receptors co-expressed with MORs in the same cell induced a selective
      and dose-dependent phosphorylation of T370 that specifically requires the
      PKCalpha isoform. Inhibition of PKC activity did not compromise homologous
      agonist-driven T370 phosphorylation. In addition, S363 was constitutively
      phosphorylated in both HEK293 cells and mouse brain in vivo. Constitutive S363
      phosphorylation required ongoing PKC activity. When basal PKC activity was
      decreased, S363 was also a substrate for homologous agonist-stimulated
      phosphorylation. CONCLUSIONS AND IMPLICATIONS: Our results have disclosed novel
      mechanisms of heterologous regulation of MOR phosphorylation by PKC. These
      findings represent a useful starting point for definitive experiments elucidating
      the exact contribution of PKC-driven MOR phosphorylation to diminished MOR
      responsiveness in morphine tolerance and pathological pain.

PMID- 24308894
TI  - Predictive value of prospective memory for remission in first-episode
      schizophrenia.
AB  - PURPOSE: The study examined the rate of remission in individuals experiencing a
      first episode of schizophrenia (FES) in China and explored predictors of
      remission in the acute phase of the illness. DESIGN AND METHODS: Fifty-five FES
      patients were randomly treated with risperidone, olanzapine, or aripiprazole at
      therapeutic doses for 8 weeks, and their clinical profiles and cognition were
      assessed using standardized assessment instruments at entry and the end of the
      study. FINDINGS: Of the 55 patients, 30 (54.5%) remitted by the end of the 8-week
      study. In univariate analyses, shorter duration of untreated psychosis, higher
      scores on both the time-based prospective memory (TBPM) and event-based
      prospective memory tasks and the Hopkins Verbal Learning Test-revised, and less
      severe negative symptoms were significantly associated with remission. In
      stepwise multiple logistic regression analyses, only higher scores on the TBPM
      significantly predicted remission. Individuals having higher scores reflecting
      better TBPM at baseline were more likely to achieve remission after 8 weeks of
      optimized antipsychotic treatment. PRACTICE IMPLICATIONS: TPBM may be useful in
      helping clinicians identify those FES patients most likely to achieve a favorable
      treatment response.

PMID- 24308895
TI  - Parental factors associated with depression and anxiety in young people: a
      systematic review and meta-analysis.
AB  - BACKGROUND: There is a burgeoning and varied literature examining the
      associations between parental factors and depression or anxiety disorders in
      young people. However, there is hitherto no systematic review of this complex
      literature with a focus on the 12-18 years age range, when the first onset for
      these disorders peaks. Furthermore, to facilitate the application of the evidence
      in prevention, a focus on modifiable factors is required. METHODS: Employing the
      PRISMA method, we conducted a systematic review of parental factors associated
      with depression and anxiety disorders in young people which parents can
      potentially modify. RESULTS: We identified 181 articles altogether, with 140
      examining depression, 17 examining anxiety problems, and 24 examining both
      outcomes. Stouffer's method of combining p values was used to determine whether
      associations between variables were reliable, and meta-analyses were conducted to
      estimate the mean effect sizes of associations between each parental factor and
      outcome. LIMITATIONS: Limitations include sacrificing micro-level detail for a
      macro-level synthesis of the literature, not systematically reviewing moderators
      and mediators, the lack of generalizability across cultures and to younger or
      adult children, and the inability to conduct a meta-analysis on all included
      studies. CONCLUSIONS: Parental factors with a sound evidence base indicating
      increased risk for both depression and anxiety include less warmth, more inter
      parental conflict, over-involvement, and aversiveness; and for depression
      additionally, they include less autonomy granting and monitoring.

PMID- 24308896
TI  - Atopic disorders and depression: findings from a large, population-based study.
AB  - BACKGROUND: Atopy, a common disorder characterized by a sensitivity to allergic
      reactions, affects a large proportion of the adult population and, as with
      depression, is associated with immune-inflammatory pathway changes. We sought to
      determine the role of atopic disorders in depression using data from a randomly
      selected, population-based study of men and women. METHODS: Cross-sectional data
      derived from the Geelong Osteoporosis Study for 942 males and 1085 females were
      analyzed. Depression [major depressive disorder (MDD), minor depression and
      dysthymia] was assessed using the Structured Clinical Interview for DSM-IV-TR
      Research Version, Non-patient edition. Data on medical conditions, including
      atopic disorders (asthma, hay fever and eczema), smoking status, alcohol
      consumption, socioeconomic status, and physical activity were documented by self
      report. Logistic regression modeling was used to explore the associations between
      atopic disorders and depression. RESULTS: Atopic disorders were associated with a
      59% increased likelihood of depression [gender and smoking-adjusted odds ratio
      (OR) 1:50, 95% CI 1.20-1.97]. Sub-group analyses revealed a similar pattern for
      those with MDD [gender and smoking-adjusted OR 1:54, 95% CI 1.22-1.94]. These
      associations were independent of socio-demographic characteristics, clinical and
      lifestyle factors. LIMITATIONS: Reliance on self-report for allergic symptoms and
      cross-sectional nature of study. CONCLUSION: This population-based study provides
      evidence of the potential contribution of allergic disorders to depression.
      Further research is required to elucidate the direction of this association and
      to further explicate its underlying physiology, including immune-inflammation
      markers.

PMID- 24308897
TI  - The pathophysiology of fluid and electrolyte balance in the older adult surgical
      patient.
AB  - BACKGROUND & AIMS: Age-related physiological changes predispose even the healthy
      older adult to fluid and electrolyte abnormalities which can cause morbidity and
      mortality. The aim of this narrative review is to highlight key aspects of age
      related pathophysiological changes that affect fluid and electrolyte balance in
      older adults and underpin their importance in the perioperative period. METHODS:
      The Web of Science, MEDLINE, PubMed and Google Scholar databases were searched
      using key terms for relevant studies published in English on fluid balance in
      older adults during the 15 years preceding June 2013. Randomised controlled
      trials and large cohort studies were sought; other studies were used when these
      were not available. The bibliographies of extracted papers were also searched for
      relevant articles. RESULTS: Older adults are susceptible to dehydration and
      electrolyte abnormalities, with causes ranging from physical disability
      restricting access to fluid intake to iatrogenic causes including polypharmacy
      and unmonitored diuretic usage. Renal senescence, as well as physical and mental
      decline, increase this susceptibility. Older adults are also predisposed to water
      retention and related electrolyte abnormalities, exacerbated at times of
      physiological stress. Positive fluid balance has been shown to be an independent
      risk factor for morbidity and mortality in critically ill patients with acute
      kidney injury. CONCLUSIONS: Age-related pathophysiological changes in the
      handling of fluid and electrolytes make older adults undergoing surgery a high
      risk group and an understanding of these changes will enable better management of
      fluid and electrolyte therapy in the older adult.

PMID- 24308898
TI  - Intensive care readmission: a contemporary review of the literature.
AB  - ICU readmissions are a commonly used quality measure but despite decades of
      research, these adverse events continue to occur. Of particular concern is that
      readmitted patients have much worse prognoses than those not readmitted. In
      recent years new clinical service roles have evolved to assist ward staff with
      the care of acutely ill patients, such as those discharged from ICU. Given the
      recent emergence of these service roles, a review of contemporary ICU readmission
      studies was warranted to determine their impact on this adverse event. Reviewed
      studies indicated the incidence of readmissions and outcomes of these patients
      have changed little in recent years. Few studies mentioned whether clinical
      service roles existed to support ward staff caring for patients recently
      discharged from ICU. Future research needs to focus on identifying modifiable
      factors in care processes to reduce the incidence and outcomes of this adverse
      event and to determine how clinical service roles can best help prevent its
      occurrence. 

PMID- 24308899
TI  - Psychological wellbeing, health related quality of life and memories of intensive
      care and a specialised weaning centre reported by survivors of prolonged
      mechanical ventilation.
AB  - OBJECTIVE: To compare memories and recall of intensive care unit and specialised
      weaning centre admission, characterise health-related quality of life and
      psychological morbidity, and examine the relationship between delusional memories
      and psychological outcomes. METHODS: We recruited participants following
      hospitalisation that included ICU admission and subsequent weaning in a
      specialised centre. We administered validated questionnaires to assess memory and
      recall of both care locations, anxiety, depression, post-traumatic stress
      symptomatology and health-related quality of life. RESULTS: Of 53 eligible
      patients discharged from the weaning centre over seven years, we recruited 27
      participants. Participants had similar numbers of factual and feeling memories
      but reported more delusional memories for ICU than the weaning centre (1.6 vs.
      0.7, P=0.004). Nine (39%) participants scored >= 11 on the hospital anxiety and
      depression scale (anxiety) and were more likely to experience delusional memories
      (P=0.008). Thirst (70%), no control (70%), noise (65%) were most frequently
      recalled ICU experiences. Procedures (83%), night awakening (70%), inability to
      sleep (70%) most frequently recalled from the weaning centre. CONCLUSION:
      Delusional memories and anxiety disorder were prevalent and associated suggesting
      interventions to ameliorate delusional memories may reduce anxiety. Difficulty
      sleeping and thirst were common experiences.

PMID- 24308900
TI  - Reaction to Jonathan Silverman.

PMID- 24308901
TI  - The relationship between caregiver functional oral health literacy and child oral
      health status.
AB  - OBJECTIVE: To describe the relationship between caregivers' oral health literacy
      (OHL) and the oral health status of their children in an Asian population.
      METHODS: A random sample of 301 child/caregiver dyads was recruited from
      kindergartens in Hong Kong. Two locally-developed and validated OHL assessment
      tasks were administered to caregivers with Hong Kong Rapid Estimate of Adult
      Literacy in Dentistry-30 (HKREALD-30) assessing word recognition and Hong Kong
      Oral Health Literacy Assessment Task for Paediatric Dentistry (HKOHLAT-P)
      assessing comprehension. Their children's oral health status was assessed [dental
      caries experience - decayed, missing, filled teeth index - (dmft) and oral
      hygiene status - Visible Plaque Index (VPI)]. RESULTS: Caregivers' literacy was
      associated with children's oral health status. The HKOHLAT-P had a stronger
      association with children's oral health than HKREALD-30. HKOHLAT-P and HKREALD-30
      remained associated with dmft in the adjusted negative binomial regression models
      (accounting for socio-demographics), Incidence Rate Ratio (IRR) 0.97, p=0.02, and
      0.96, p=0.03, respectively. In the adjusted model, HKOHLAT-P was associated with
      VPI (IRR 0.90, p<0.05), but no association between HKREALD-30 and VPI was
      evident. CONCLUSION: The main conclusion of this study was that caregiver oral
      health literacy was associated with their child's oral health status. A
      comprehension instrument had a more robust association with children's oral
      status than a word recognition instrument. PRACTICE IMPLICATIONS: This study has
      implications for general public health education for designing community-level
      interventions.

PMID- 24308902
TI  - Depression in palliative care patients: a survey of assessment and treatment
      practices of Australian and New Zealand palliative care specialists.
AB  - OBJECTIVE: To explore the practices of members of the Australian and New Zealand
      Society of Palliative Medicine (ANZSPM) in assessing and treating depression in
      palliative care patients. METHODS: Semistructured questionnaires were forwarded
      to ANZSPM members in consecutive mail-outs to survey diagnostic and treatment
      practices for depression. RESULTS: The response rate was 62.3%. The median
      prevalence of depression, as perceived by respondents, in the present respondent
      patient populations was 20% (range 0%-90%); 57.1% of respondents always assessed
      for depression, whereas 42.9% assessed for depression sometimes. The majority
      (98.9%) of respondents relied on clinical interviews to assess depression; non
      somatic symptoms of the Diagnostic and Statistical Manual of Mental Disorders,
      4th edition (DSM-IV) criteria were more useful than somatic symptoms. The
      depression screening tools most frequently used were one- and two-item questions.
      Pharmacological and non-pharmacological methods were used to treat depression,
      with selective serotonin reuptake inhibitors the most frequently prescribed
      medications. Psycho-educational and supportive counselling were the most
      frequently used non-pharmacological interventions. Nominated measures to augment
      depression management included improving access to psychiatry, psychology and
      other allied health services, the development of a screening tool specific to
      palliative care patients and associated guidelines for depression management.
      CONCLUSIONS: This is the first Australasian study to explore the practice of
      medical practitioners regarding depression in palliative patients. Incorporation
      of screening tool questions into palliative care assessment interviews may
      warrant future research. WHAT IS KNOWN ABOUT THE TOPIC? Depression in palliative
      care patients has a negative impact on quality of life; however, little is known
      about how Australasian palliative care medical practitioners manage depression in
      this patient population. WHAT DOES THIS PAPER ADD? To the researchers' knowledge,
      this is the first Australasian study that explores the practices of local
      palliative care specialists in the management of depression in palliative
      patients. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Overall management of
      depression in palliative care populations by Australasian practitioners is
      similar to that of their European colleagues. Consensus is that for assessment of
      depression in palliative patients, non-somatic symptoms of DSM-IV criteria are
      more useful than somatic symptoms. Practitioners report the need for improved
      access to psychiatric, psychological and other support services, for a palliative
      care-specific depression screening tool and for depression management guidelines
      applicable to palliative care patients.

PMID- 24308903
TI  - Perceived difficulty in the use of everyday technology: relationships with
      everyday functioning in people with acquired brain injury with a special focus on
      returning to work.
AB  - PURPOSE: The aim was to explore the relationships between difficulties in the use
      of everyday technology (ET) and the ability to perform activities of daily life
      (ADL) in the home and in society and in the workplace in people with acquired
      brain injury (ABI). METHOD: The investigation comprises an explorative cross
      sectional study of 74 people with ABI. The short version of the Everyday
      Technology Use Questionnaire (S-ETUQ) and a revised version of the ADL taxonomy
      were used to evaluate the participants. Rasch-generated person ability measures
      of ET use and ADL were used in correlation analyses, in group comparisons by
      ANOVA and in logistic regressions. RESULTS: Difficulty in the use of ET was
      significantly correlated with ADL limitations. People who worked full- or part
      time had significantly higher ability to use ET than those with some type of full
      time, long-term sickness compensation. The ability to use ET, ADL ability and age
      were significantly related to return to work. CONCLUSION: The ability to use ET
      is related to all areas of everyday functioning in people with ABI. Therefore, a
      patient's ability to use ET needs to be considered in rehabilitation strategies
      following an ABI to enhance the patient's performance of activities in the home
      and in society and to support his or her likelihood of returning to work.

PMID- 24308904
TI  - A multi-method approach to studying activity setting participation: integrating
      standardized questionnaires, qualitative methods and physiological measures.
AB  - PURPOSE: This study investigated the feasibility of integrating three diverse
      methods for studying disabled youth's experiences of activity settings:
      standardized questionnaires, qualitative methods and physiological measures. The
      article describes a case study of data collection in a real-life setting to
      outline the opportunities, challenges and lessons learned for future research.
      METHODS: The methods included (a) two newly developed quantitative measures of
      qualities of home and community activity settings (MEQAS) and youth experiences
      (SEAS); (b) youth-friendly qualitative methods, including photo-elicitation,
      observations, electronic interviews and face-to-face interviews; and (c) an
      innovative system to collect physiological data (the HEART system) that provided
      insight into the experiences of youth beyond other methods. RESULTS: The study
      demonstrated that these diverse methods measures can be practically combined to
      study activity setting participation experiences. The measures provided different
      types of data that informed one other and allowed a rich interpretation and deep
      understanding of the participant's experiences. We discuss practical lessons
      concerning the joint use of the three methods, lessons specific to each method,
      and lessons concerning next steps for integrating the data. CONCLUSIONS: Combined
      methodologies hold great promise for investigations of the participation
      experiences of disabled youth in future research.

PMID- 24308905
TI  - Obesity prevention for children with physical disabilities: a scoping review of
      physical activity and nutrition interventions.
AB  - PURPOSE: Children with disabilities are at higher risk of obesity, engage in less
      physical activity and report poorer quality dietary habits than their non
      disabled peers. This study reviewed current evidence on interventions designed to
      facilitate weight management and/or weight-related behaviors (i.e. physical
      activity and/or healthy eating habits) in children with physical disabilities.
      METHODS: A scoping review was performed using established methodology. Data from
      studies meeting specific inclusion criteria were extracted and analyzed using
      summary statistics, and common characteristics thematically identified. RESULTS:
      Thirty-four articles were included in the synthesis. No long-term obesity
      prevention interventions were identified. The majority of research focused upon
      children with cerebral palsy, and had case study, quasi- or non-experimental
      designs. All interventions reporting positive outcomes (n = 18) addressed
      physical activity, with common themes including using motivational strategies for
      the child and child self-direction. Incremental increases in workload and
      engaging in strength training for longer than 15 minutes were also effective.
      Interventions targeting body weight/composition did not report success in the
      long term. CONCLUSIONS: A robust evidence base is lacking for long-lasting
      obesity interventions for children with physical disabilities. Current research
      provides some insights into the specific components that should be considered
      when planning such interventions in the future.

PMID- 24308906
TI  - Activity problems in everyday life--patients' perspectives of hand
      osteoarthritis: "try imagining what it would be like having no hands".
AB  - PURPOSE: To explore first-person perspectives on activities and participation in
      everyday life among people with hand osteoarthritis (OA). METHOD: Semi-structured
      interviews were carried out with 5 men and 26 women of different ages living with
      hand OA. Supplemental data were collected via photo-interviews of two of the men
      and nine of the women. The analytical process was inspired by the interpretive
      phenomenological analysis and informed by the interpretive frameworks of critical
      psychology and social practice theory. RESULTS: Empirical findings indicate that
      persons with hand OA experience activity problems and participation limitations
      in the conduct of everyday life. Activity problems were related to self-care,
      paid work, as well as leisure activities. The participants also reported
      employing different strategies attempting to overcome the challenges of their
      everyday lives in order to keep actively performing valued activities. They
      reported environmental support of utmost importance for these attempts. Social
      participation in networks was also reported to be affected by the participants'
      activity problems. CONCLUSIONS: Arranging everyday life is complex and is carried
      out in structures of social practice. A supportive physical and social
      environment facilitates participation. The findings highlight the importance of
      paying attention to individual needs in rehabilitation processes.

PMID- 24308907
TI  - The enhancement of clinical competence through caring science.
AB  - This theoretical research attempts to create a new basis for dialogue between two
      independent research fields that are connected by an inseparable link. The first,
      nursing science, is a body of professional knowledge, while the second, caring as
      an independent body of pure knowledge, conducts basic research with an aspiration
      towards applicability. This theoretical research uses the guidelines of the
      Buberian dialogue, which provides new meaning to the concept of clinical
      competence. The results emphasise the need to adopt abstract knowledge into the
      nursing field in order to improve the graduate's clinical capabilities. The
      combination of assessing clinical capability in a judgmental manner together with
      the dialogical humanistic approach of caring science may create a genuine
      platform and meeting event as a maturing process, which is intended to promote
      educational goals, which subsequently receive new meaning, that is, a different
      type of assessment. However, this assessment cannot be measured since a wide
      range of ethical moral aspects regarding both the student and the patient will
      have to be included. Nevertheless, this dialogue between nursing science and
      caring science can implement evidence on the basis of trust and can be used as a
      dialogical tool for evaluating clinical skills with the goal of empowering the
      educational field in nursing. Consequently, this clinical competence is called
      'caring maturing means', and the goal is to convert the learning process into a
      meaningful event with the aim of improvement. 

PMID- 24308908
TI  - rRNA fragmentation induced by a yeast killer toxin.
AB  - Virus like dsDNA elements (VLE) in yeast were previously shown to encode the
      killer toxins PaT and zymocin, which target distinct tRNA species via specific
      anticodon nuclease (ACNase) activities. Here, we characterize a third member of
      the VLE-encoded toxins, PiT from Pichia inositovora, and identify PiOrf4 as the
      cytotoxic subunit by conditional expression in Saccharomyces cerevisiae. In
      contrast to the tRNA targeting toxins, however, neither a change of the wobble
      uridine modification status by introduction of elp3 or trm9 mutations nor tRNA
      overexpression rescued from PiOrf4 toxicity. Consistent with a distinct RNA
      target, expression of PiOrf4 causes specific fragmentation of the 25S and 18S
      rRNA. A stable cleavage product comprising the first ~ 130 nucleotides of the 18S
      rRNA was purified and characterized by linker ligation and subsequent reverse
      transcription; 3'-termini were mapped to nucleotide 131 and 132 of the 18S rRNA
      sequence, a region showing some similarity to the anticodon loop of
      tRNA(Glu)(UUC), the zymocin target. PiOrf4 residues Glu9 and His214,
      corresponding to catalytic sites Glu9 and His209 in the ACNase subunit of zymocin
      are essential for in vivo toxicity and rRNA fragmentation, raising the
      possibility of functionally conserved RNase modules in both proteins.

PMID- 24308909
TI  - Physician and patient characteristics affecting repeat use of abdominal
      ultrasound: A nationwide population-based study.
AB  - BACKGROUND: Ultrasound is a useful and popular imaging modality. Our aim was to
      assess the association between the use and repeat use of abdominal ultrasound and
      diagnosis, physicians, and hospital characteristics according to a Taiwanese
      national database. METHODS: The Taiwan National Health Insurance database
      contains data for approximately 22,134,270 insured individuals during 2004-2005
      (>98% of the population in Taiwan). Patients who were scanned with abdominal
      ultrasound once or more during that period were identified. Associations between
      physicians, hospital characteristics, diagnoses, and repeat use of abdominal
      ultrasound were analyzed. Logistic regression with generalized estimating
      equations was used. RESULTS: A total of 2,319,164 abdominal ultrasound scans were
      performed (approximately 6.42% of the population in Taiwan). Among these, 38.34%
      received repeat examinations. Multiple logistic regression analysis showed that
      gastroenterologists [odds ratio (OR) = 1.07], male physicians, physicians younger
      than 40 years of age, and physicians in medical centers were more likely to use
      repeat abdominal ultrasound. The analysis also showed that male patients, older
      patients, patients with liver and biliary disease (OR = 1.17), and patients with
      other abdominal disease (OR = 1.37) were more likely to receive repeat abdominal
      ultrasound. CONCLUSION: Our study shows that the use and repeat use of abdominal
      ultrasound is very high and is related to diagnosis and physician and hospital
      characteristics.

PMID- 24308910
TI  - [Interobserver reliability of the Glasgow coma scale in critically ill patients
      with neurological and/or neurosurgical disease].
AB  - INTRODUCTION: The Glasgow coma scale (GCS) is a common tool used for neurological
      assessment of critically ill patients. Despite its widespread use, the GCS has
      some limitations, as sometimes different observers may value differently the same
      response. OBJECTIVE: To evaluate the interobserver agreement, among intensive
      care nurses with a minimum of 3 years experience, both in the overall estimate of
      GCS and for each of its components. METHODS: Prospective observational study
      including 110 neurological and/or neurosurgical patients conducted in a critical
      care unit of 18 beds, from October 2010 until December 2012. Registered
      variables: Demographic characteristics, reason for admission, overall GCS and its
      components. The neurological evaluation was conducted by a minimum of 3 nurses.
      One of them applied an algorithm and consensual assessment technique and all,
      independently, valued response to stimuli. Interobserver agreement was measured
      using the intraclass correlation coefficient (ICC) for a confidence interval (CI)
      of 95%. The study was approved by the Ethics Committee for Clinical Trails.
      RESULTS: The intraclass correlation coefficient (confident interval) for scale
      was: Overall GCS: 0.989 (0.985-0.992); ocular response: 0.981 (0.974-0.986);
      verbal response: 0.971 (0.960-0.979); motor response: 0.987 (0.982-0.991).
      CONCLUSION: In our cohort of patients we observed a high level of consistency in
      the application of both the GCS as in each of its components.

PMID- 24308911
TI  - Long-term benzodiazepine use in patients with major depressive disorder in China.
AB  - PURPOSE: There have been no data about long-term benzodiazepine (BZD) use and its
      correlates in patients with major depressive disorder (MDD) in China. This study
      aimed to examine the prevalence of long-term BZD use (more than three months) and
      its demographic and clinical correlates in Chinese patients with MDD. DESIGN AND
      METHODS: A total of 1,192 patients with MDD were examined in 10 mental health
      centers in China. Patients' socio-demographic and clinical characteristics and
      prescriptions for psychotropic drugs were recorded using a standardized form.
      FINDINGS: A large portion of patients (36.2%) received long-term BZD treatment.
      Univariate analyses revealed that long-term BZD users were older, poorer, and had
      more impaired occupational functioning than patients not taking BZDs. Long-term
      BZD users had fewer psychotic symptoms and took less antipsychotic drugs. In
      multivariate analyses, long-term BZD use was independently associated with older
      age and more severe impaired occupational functioning; long-term BZD users were
      less likely to receive antipsychotic medications and traditional antidepressants
      (tricyclic antidepressants, tetracyclic antidepressant, and monoamine oxidase
      inhibitors). PRACTICE IMPLICATIONS: Long-term BZD use was common in patients with
      MDD in China. A host of demographic and clinical factors were independently
      associated with long-term BZD use.

PMID- 24308913
TI  - Elevated airborne manganese and low executive function in school-aged children in
      Brazil.
AB  - Exposure to airborne manganese (Mn) has been associated with neurotoxic effects,
      including motor and cognitive deficits. The main deficits related to excessive
      exposure to Mn are predominantly the dysfunction of fronto-striatal and
      dopaminergic circuits observed in animal experimental studies, which are involved
      in attention, working memory and motor function. The present study aims to assess
      the association between elevated Mn exposure and performance on executive
      function and attention neuropsychological tests in children living in two
      communities near a ferro-manganese alloy plant. Seventy children aged between 7
      and 12 years with no history of neurologic disease and an estimated IQ >68
      (Vocabulary and Block Design subtests) that had lived near the iron-Mn production
      alloy plant for at least 1.5 years were included. Participants were assessed for
      cognitive functioning with neuropsychological measures for sustained attention
      (Test of Visual Attention - TAVIS-3R), cognitive flexibility (WCST), and verbal
      and visual working memory (WISC-III Digit Span subtest and Corsi Block).
      Manganese hair (MnH) levels were used as a biomarker of exposure. Mean scores
      among study participants were lower than general population norms/averages for
      block design, digit span, reaction time and commission errors. The median MnH
      level was 11.48 (range 0.52-55.74) MUg/g, and no difference between sexes was
      observed. Spearman's correlation analysis showed a significant inverse
      correlation between MnH levels and estimated IQ (rho=-0.448, p=0.0001),
      Vocabulary (rho=-0.272, p=0.02), Block Design (rho=-0.485, p=0.00002) and Digit
      Span (rho=-0.410, p=0.0004). Multiple regression analyses detected inverse
      associations between log MnH and scores on estimated IQ (beta=-9.67; 95%CI=-16.97
      to -2.37), Block Design (beta=-2.50; 95%CI=-3.91 to -1.10) and Digit Span Total
      (beta=-2.59; 95%CI=-4.13 to -1.05) standardized scores and the number of correct
      answers in forward and backward Digit Span methods, after adjusting for
      covariates (beta=-1.32=95%CI=-2.23 to -0.40; beta=-1.09 95%CI=-2.02 to -0.16,
      respectively). The results suggest that airborne Mn exposure may be associated
      with lower IQ and neuropsychological performance in tests of executive function
      of inhibition responses, strategic visual formation and verbal working memory.
      Executive function is dependent on the fronto-striatal circuit, which may be
      disrupted by Mn accumulation in the brain. 

PMID- 24308912
TI  - Topographic and quantitative evaluation of gentamicin-induced damage to
      peripheral innervation of mouse cochleae.
AB  - Ototoxicity induced by aminoglycoside antibiotics appears to occur both in hair
      cells (HCs) and the cochlear nerves that innervate them. Although HC loss can be
      easily quantified, neuronal lesions are difficult to quantify because two types
      of afferent dendrites and two types of efferent axons are tangled beneath the
      hair cells. In the present study, ototoxicity was induced by gentamicin in
      combination with the diuretic agent furosemide. Neuronal lesions were quantified
      in cochlear whole-mount preparations combined with microsections across the
      habenular perforate (HP) openings to achieve a clear picture of the topographic
      relationship between neuronal damage and HC loss. Multiple immunostaining methods
      were employed to differentiate the two types of afferent dendrites and two types
      of efferent axons. The results show that co-administration of gentamicin and
      furosemide resulted in a typical dynamic pattern of HC loss that spread from the
      basal turn to the outer hair cells to the apex and inner hair cells, depending on
      the dose and survival time after drug administration. Lesions of the innervation
      appeared to occur at two stages. At the early stage (2-4 days), the loss of
      labeling of the two types of afferent dendrites was more obvious than the loss of
      labeled efferent axons. At the late stage (2-4 weeks), the loss of labeled
      efferent axons was more rapid. In the high-dose gentamicin group, the loss of
      outer HCs was congruent with afferent dendrite loss at the early stage and
      efferent axon loss at the late stage. In the low-dose gentamicin group, the loss
      of labeling for cochlear innervation was more severe and widespread. Thus, we
      hypothesize that the gentamicin-induced damage to cochlear innervation occurs
      independently of hair cell loss. 

PMID- 24308914
TI  - Nicotinamide adenine dinucleotide prevents neuroaxonal degeneration induced by
      manganese in cochlear organotypic cultures.
AB  - Manganese (Mn) is an essential trace mineral for normal growth and development.
      Persistent exposures to high atmospheric levels of Mn have deleterious effects on
      CNS and peripheral nerves including those associated with the auditory system.
      Nicotinamide adenine dinucleotide (NAD) is a coenzyme which functions in the
      electron transfer system within the mitochondria. One of the most notable
      protective functions of NAD is to delay axonal degenerations caused by various
      neurodegenerative injuries. We hypothesized that NAD might also protect auditory
      nerve fibers (ANF) and SGN from Mn injury. To test this hypothesis, cochlear
      organotypic cultures were treated with different doses of Mn (0.5-3.0 mM) alone
      or combined with 20 mM NAD. Results demonstrate that the percentage of hair
      cells, ANF and SGN decreased with increasing Mn concentration. The addition of 20
      mM NAD did not significantly reduce hair cells loss in the presence of Mn,
      whereas the density of ANF and SGN increased significantly in the presence of
      NAD. NAD suppressed Mn-induced TUNEL staining and caspase activation suggesting
      it prevents apoptotic cell death. These results suggest that excess Mn has
      ototoxic and neurotoxic effects on the auditory system and that NAD may prevent
      Mn-induced axonal degeneration and avoid or delay hearing loss caused by excess
      Mn exposure.

PMID- 24308915
TI  - Perspectives of Indigenous people in the Pilbara about the delivery of healthcare
      services.
AB  - AIM: To identify Indigenous people's views about gaps and practical solutions for
      the delivery of healthcare services in the Pilbara. METHODS: A structured guide
      was used to interview three Indigenous language groups from the Pilbara region of
      Western Australia. The responses were analysed with the use of content analysis.
      In the first stage, codes were developed by assigning names to small sections of
      the interview transcripts. Next, the most salient incisive codes were identified
      and developed into themes that captured the most important issues. RESULTS: Many
      respondents said that there were insufficient health professionals near country,
      which was compounded by a lack of adequate transport to reach healthcare
      services. Moreover, respondents commonly indicated that they would be unable to
      secure adequate accommodation for themselves and any carer when needing to leave
      country to undergo medical care. The importance of secondary healthcare
      interventions was highlighted, particularly health promotion initiatives that
      improved diet and exercise levels and reduced substance abuse. Assuming
      responsibility for one's own health was seen as integral to improving the overall
      health of communities. The respondents saw role models as the most important
      influence in leading people to take responsibility for improving their own
      health. CONCLUSION: This study provides Indigenous perspectives about gaps and
      solutions in healthcare service delivery in the Pilbara region of Western
      Australia. Although initiatives have commenced to address the shortfall in health
      professionals and inadequate transport to healthcare, there are still gaps in
      service provision. Mobile health services were strongly supported as an integral
      measure to address these gaps. WHAT IS KNOWN ABOUT THIS TOPIC? About two out of
      every three Indigenous adults in the Pilbara experience a chronic health
      condition. Moreover, compared with non-Indigenous people in the region,
      Indigenous people experience a significantly higher mortality rate for numerous
      chronic health conditions. Although some information is available about the
      provision of health services for Indigenous people in the Pilbara, little is
      known about Indigenous people's perspectives about its adequacy or how it should
      be delivered. WHAT DOES THIS PAPER ADD? This study details three local language
      groups' views about the gaps and solutions to delivery of healthcare for
      Indigenous people in the Pilbara. It highlights the need for secondary healthcare
      interventions given difficulties around providing adequate primary care in remote
      settings. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Health promotion
      initiatives need to be prioritised to improve the health of Australian Indigenous
      people in the Pilbara and the initiatives should be delivered with the
      involvement of the local communities. Innovative solutions are required to
      improve the continuity of healthcare in the Pilbara, including increased use of
      mobile services.

PMID- 24308916
TI  - Identification of the phosphorylated residues in TveIF5A by mass spectrometry.
AB  - The initiation factor eIF5A in Trichomonas vaginalis (TveIF5A) is previously
      shown to undergo hypusination, phosphorylation and glycosylation. Three different
      pI isoforms of TveIF5A have been reported. The most acidic isoform (pI 5.2)
      corresponds to the precursor TveIF5A, whereas the mature TveIF5A appears to be
      the most basic isoform (pI 5.5). In addition, the intermediary isoform (pI 5.3)
      is found only under polyamine-depleted conditions and restored with exogenous
      putrescine. We propose that differences in PI are due to phosphorylation of the
      TveIF5A isoforms. Here, we have identified phosphorylation sites using mass
      spectrometry. The mature TveIF5A contains four phosphorylated residues (S3, T55,
      T78 and T82). Phosphorylation at S3 and T82 is also identified in the
      intermediary TveIF5A, while no phosphorylated residues are found in the precursor
      TveIF5A. It has been demonstrated that eIF5A proteins from plants and yeast are
      phosphorylated by a casein kinase 2 (CK2). Interestingly, a gene encoding a
      protein highly similar to CK2 (TvCK2) is found in T. vaginalis, which might be
      involved in the phosphorylation of TveIF5A in T. vaginalis. 

PMID- 24308917
TI  - Development and usage of protein microarrays for the quantitative measurement of
      Panton-Valentine leukocidin.
AB  - Staphylococcus aureus is a human pathogen that can harbour several genes encoding
      exotoxins including leukocidins. A clinically most relevant factor is Panton
      Valentine leukocidin (PVL) because of its association with chronic, recurrent or
      severe skin and soft tissue infections. In this study an antibody array was
      designed and used to obtain an overview about the in vitro PVL expression levels
      of 266 clinical isolates of MRSA as well as of MSSA belonging to a wide variety
      of clonal complexes. For that purpose, a novel precipitation based method was
      used. Unknown PVL concentrations were determined by mapping the signal
      intensities for spotted monoclonal antibodies to calibration curves that resulted
      from experiments with known concentrations of recombinant LukF-PV. In most cases,
      isolates belonging to one clonal complex (CC) showed similar PVL expressions.
      However, there were also CCs with widely varying PVL concentrations. First
      analyses, based on in vitro PVL measurements, showed low PVL concentrations in
      isolates from severe and fatal conditions that are not associated with PVL, such
      as sepsis, while isolates from skin and soft tissue infections yielded higher
      concentrations. Agr-group I and IV isolates generally produced more PVL than
      isolates from agr-groups II and III. The few isolates harbouring the gene
      encoding toxic shock syndrome toxin (tst1) were particularly low level PVL
      producers. However, these issues warrant further studies. The method described
      herein allows rapid quantification of expressed proteins such as PVL in
      collections of clinical isolates in order to correlate with clinical or genotypic
      data with a potential for further parallelisation.

PMID- 24308918
TI  - Minimal effects of waterborne exposure to single-walled carbon nanotubes on
      behaviour and physiology of juvenile rainbow trout (Oncorhynchus mykiss).
AB  - Fish behaviours are often considered to be sensitive endpoints of waterborne
      contaminants, but little attention has been given to engineered nanomaterials.
      The present study aimed to determine the locomotor and social behaviours of
      rainbow trout (Oncorhynchus mykiss) during waterborne exposure to single-walled
      carbon nanotubes (SWCNTs), and to ascertain the physiological basis for any
      observed effects. Dispersed stock suspensions of SWCNTs were prepared by stirring
      in sodium dodecyl sulphate (SDS), an anionic surfactant, on an equal w/w basis.
      Trout were exposed to control (no SWCNT or SDS), 0.25 mg L(-1) SDS (dispersant
      control), or 0.25 mg L(-1) of SWCNT for 10 days. Video tracking analysis of
      spontaneous locomotion of individual fish revealed no significant effects of
      SWCNT on mean velocity when active, total distance moved, or the distribution of
      swimming speeds. Hepatic glycogen levels were also unaffected. Fish exposed to
      SWCNTs retained competitive fitness when compelled to compete in energetically
      costly aggressive interactions with fish from both control groups. Assessment of
      the respiratory physiology of the fish revealed no significant changes in
      ventilation rate or gill injuries. Haematocrit and haemoglobin concentrations in
      the blood were unaffected by SWCNT exposure; and the absence of changes in the
      red and white pulp of the spleen excluded a compensatory haematopoietic response
      to protect the circulation. Despite some minor histological changes in the
      kidneys of fish exposed to SWCNT compared to controls, plasma ion concentrations
      and tissue electrolytes were largely unaffected. Direct neurotoxicity of SWCNT
      was unlikely with the brains showing mostly normal histology, and with no effects
      on acetylcholinesterase or Na(+)/K(+)-ATPase activities in whole brain
      homogenates. The minimal effects of waterborne exposure to SWCNT observed in this
      study are in contrast to our previous report of SWCNT toxicity in trout,
      suggesting that details of the dispersion method and co-exposure concentration of
      the dispersing agent may alter toxicity.

PMID- 24308919
TI  - Investigating personality and conceptualising allied health as person or
      technique oriented.
AB  - OBJECTIVE: Allied health (AH) includes many diverse professions, each with a
      unique contribution to healthcare, making it possible to consider these
      professions as person oriented (PO) or technique oriented (TO). This paper
      explored the personality traits of AH professionals from the perspective of both
      the PO or TO orientation and the individual professions. METHODS: AH
      professionals (n=562) provided demographic data and completed the Temperament and
      Character Inventory. Examination of the literature and a consultation process
      resulted in nine professions classified as PO and 10 classified as TO.
      Multivariate analyses compared levels of personality traits and demographic
      variables between the PO (n=492) and TO (n=70) groups, and the professions within
      the groups. RESULTS: Professionals in the PO group showed significantly higher
      levels of traits that emphasise person orientation attributes, such as being
      sociable, empathic and cooperative, compared with AH professionals in professions
      with an emphasis on TO. CONCLUSIONS: Trends in personality traits among AH
      professionals were congruent with the PO and TO aspects of their chosen
      profession. This supports the usefulness of the PO and TO concepts in describing
      AH professions and may provide new clues for policy aiming to enhance job
      satisfaction, retention and career development. WHAT IS KNOWN ABOUT THE TOPIC?
      The literature suggests that certain medical specialities can be classified as
      person (PO) or technique oriented (TO) and that individuals attracted to those
      specialties display traits that are similar to that orientation. There is scant
      information on the AH professions regarding similar person or technique
      orientations. WHAT DOES THIS PAPER ADD? The diversity of professions within AH
      allows a new approach to describing each profession as either PO (socially
      dependent, cooperative and relationship focused), or TO (focused on skills and
      procedures). The trend in personality traits of individuals in certain AH
      professions is compatible with the orientation of that profession. Findings
      suggest that individuals may be attracted to professions that favour a similar
      personality pattern to their own. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?
      Gaining an improved understanding of the AH professions and individuals who are
      attracted to them in a climate of workforce shortage and increasing
      multidisciplinary service demand. The findings provide a new approach to
      understanding the characteristics of AH professions according to the
      personalities they attract. This information could guide recruitment and
      retention policy, and assist in career counselling by providing greater insight
      into personality profiles that are best suited to certain professions.

PMID- 24308920
TI  - Frequency of physical restraint and its associations with demographic and
      clinical characteristics in a Chinese psychiatric institution.
AB  - PURPOSE: Physical restraint (PR) is a highly controversal topic in psychiatry.
      Little is known about PR among psychiatric inpatients in China. This study
      examined the frequency of PR and its relationships with demographic and clinical
      characteristics among a large psychiatric institution in the Hunan Province,
      China. DESIGN AND METHODS: The study included a consecutively assessed sample of
      160 psychiatric inpatients. Sociodemographic and clinical data including use of
      PR were collected from the medical records using a form designed for this study
      and confirmed via interview. FINDINGS: The frequency of PR was 51.3% in the whole
      sample; 63.2% among female and 39.2% among male patients. In multiple logistic
      regression analysis PR was independently associated with male gender (p = 0.001,
      odds ratio [OR] = 0.2, 95% confidence interval [CI] 0.1-0.6), less outpatient
      treatment prior to admission (p = 0.03, OR = 0.3, 95% CI 0.1-0.9), more frequent
      use of mood stabilizers (p = 0.002, OR = 5.6, 95% CI 1.9-16.7), more aggressive
      behavior prior to admission (p = 0.002, OR = 1.1, 95% CI 1.04-1.2), and younger
      age (p = 0.04, OR = 0.97, 95% CI 0.93-0.99). PRACTICE IMPLICATIONS: PR is very
      common in clinical practice in China. Its demographic and clinical correlates are
      similar to findings in Western settings.

PMID- 24308921
TI  - Establishing the value of Indigenous eye health programs: health needs, economic
      priority and performance assessment approaches.
AB  - OBJECTIVES: The aim of this paper was to compare three different approaches that
      are used in support of additional funding of health programs, using Indigenous
      eye health programs (IEHPs) as an example. These approaches are Heath and Health
      Care Needs, Economic Priority (Value for Money) and Conformity with Health
      Services Performance Standards. METHODS: A review of relevant literature was
      conducted to identify relevant benchmarks and assess IEHPs. RESULTS: In terms of
      health needs, vision loss is the fourth highest contributor to the Indigenous
      health gap. Additional funding for Indigenous eye treatment services to remove
      the gap is estimated at A$28.1million per annum. As an economic priority, IEHPs
      (specifically for refractive error, cataract, diabetic retinopathy and trachoma)
      demonstrate excellent value for money and compare favourably with other better
      researched health programs. Evaluation of health performance measures indicated
      that IEHPs also perform well, as judged by Australian performance standards for
      health services generally and Indigenous health services more specifically, the
      later involving local delivery, including care coordination through Aboriginal
      controlled community health services. CONCLUSION: The value of IEHPs was
      demonstrated using all three approaches. Different approaches are likely to be
      more or less persuasive with different audiences. The application of these
      approaches is relevant to other health programs. WHAT IS KNOWN ABOUT THIS TOPIC?
      Supporters of additional funding for health programs frequently use the impact of
      this additional funding on the health and health care needs of the affected
      populations and individuals. Indigenous Eye Health programs are considered for
      illustrative purposes. This argument is not necessarily persuasive to funders of
      health programs. WHAT DOES THIS PAPER ADD? This paper demonstrates that two
      further approaches, namely Economic Priority and Conformity with Health
      Performance Measure Standards, both demonstrate good arguments in support of
      additional funding and that these outcomes may be more persuasive to funders of
      health programs. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Practitioners are
      able to harness additional approaches with a higher likelihood of success of
      submissions for additional funding for the program they are promoting.

PMID- 24308922
TI  - Management of low back pain.

PMID- 24308923
TI  - Health collaboration between BBC and Bihar government is to expand to new areas.

PMID- 24308924
TI  - Solution-processed PEDOT:PSS films with conductivities as indium tin oxide
      through a treatment with mild and weak organic acids.
AB  - New transparent conductive materials are urgently needed for optoelectronic
      devices. Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) will
      be a promising next-generation transparent electrode material if its conductivity
      is comparable to that of indium tin oxide (ITO). To enhance significantly the
      conductivity of PEDOT:PSS with mild compounds has practical significance. In this
      work, significant conductivity enhancements are achieved on PEDOT:PSS films after
      treatment with mild and weak organic acids. The treated PEDOT:PSS films exibit
      metallic behavior at room temperature. Their conductivity increases to about 3300
      S cm(-1) after they are treated with 8 M methanesulfonic acid. The conductivity
      enhancement depends on the acidity and physical properties of the organic acids.
      The mechanism for the conductivity enhancement is ascribed to proton transfer
      from the mild or weak organic acids to PSS(-) of PEDOT:PSS. There are two factors
      for the proton transfer from mild or weak organic acids to PSS. One factor is the
      high acid concentration during the treatment, particularly after the vaporization
      of the water solvent. Another factor is the phase segregation of PSSH from
      PEDOT:PSS, because PSSH is hydrophilic, whereas PEDOT is hydrophobic. This method
      is better than that using very strong and corrosive acids like sulfuric acid.
      These highly conductive and highly transparent PEDOT:PSS films are promising for
      use as next-generation transparent electrodes. 

PMID- 24308925
TI  - Estimating treatment rates for mental disorders in Australia.
AB  - OBJECTIVE: To estimate the percentage of Australians with a mental disorder who
      received treatment for that disorder each year between 2006-07 and 2009-10.
      METHODS: We used: (1) epidemiological survey data to estimate the number of
      Australians with a mental disorder in any year; (2) a combination of
      administrative data on people receiving mental health care from the Commonwealth
      and State and Territories and epidemiological data to estimate the number
      receiving treatment; and (3) uncertainty modelling to estimate the effects of
      sampling error and assumptions on these estimates. RESULTS: The estimated
      population treatment rate for mental disorders in Australia increased from 37% in
      2006-07 to 46% in 2009-10. The model estimate for 2006-07 (37%) was very similar
      to the estimated treatment rate in the 2007 National Survey of Mental Health and
      Wellbeing (35%), the only data available for external comparison. The uncertainty
      modelling suggested that the increased treatment rates over subsequent years
      could not be explained by sampling error or uncertainty in assumptions.
      CONCLUSIONS: The introduction of the Commonwealth's Better Access initiative in
      November 2006 has been the driver for the increased the proportion of Australians
      with mental disorders who received treatment for those disorders over the period
      from 2006-07 to 2009-10. WHAT IS KNOWN ABOUT THE TOPIC? Untreated mental
      disorders incur major economic costs and personal suffering. Governments need
      timely estimates of treatment rates to assess the effects of policy changes aimed
      at improving access to mental health services. WHAT DOES THIS PAPER ADD? Drawing
      upon a combination of epidemiological and administrative data sources, the
      present study estimated that the population treatment rate for mental disorders
      in Australia increased significantly from 37% in 2006-07 to 46% in 2009-10. WHAT
      ARE THE IMPLICATIONS FOR PRACTITIONERS? Increased access to services is not
      sufficient to ensure good outcomes for those with mental disorders. It is also
      important to ensure that evidence-based treatment is provided to those
      Australians accessing these services.

PMID- 24308926
TI  - Life stress and family history for depression: the moderating role of past
      depressive episodes.
AB  - Three of the most consistently reported and powerful predictors of depression are
      a recent major life event, a positive family history for depression, and a
      personal history of past depressive episodes. Little research, however, has
      evaluated the inter-relations among these predictors in depressed samples. Such
      information is descriptively valuable and potentially etiologically informative.
      In the present article we summarize the existing literature and test four
      predictions in a sample of 62 clinically depressed individuals: (1) participants
      who experienced a major life event prior to onset would be less likely than
      participants who did not experience a major life event to have a positive family
      history for depression; (2) participants with a recent major life event would
      have fewer lifetime episodes of depression than would participants without; (3)
      participants with a positive family history for depression would have more
      lifetime episodes of depression than would participants with a negative family
      history for depression; and (4) we would obtain a 3-way interaction in which
      participants with a positive family history and without a major life event would
      have the most lifetime episodes, whereas participants with a negative family
      history and a major life event would have the fewest lifetime episodes. The first
      three predictions were confirmed, and the fourth prediction partially confirmed.
      These novel findings begin to elucidate the complex relations among these three
      prominent risk factors for depression, and point to avenues of research that may
      help illuminate the origins of depressive episodes. 

PMID- 24308927
TI  - Ustekinumab for hidradenitis suppurativa: a case report.

PMID- 24308928
TI  - Breed differences in insulin sensitivity and insulinemic responses to oral
      glucose in horses and ponies of moderate body condition score.
AB  - Breed-related differences may occur in the innate insulin sensitivity (SI) of
      horses and ponies, an important factor believed to be associated with the risk of
      laminitis. The aim of this study was to measure the glucose and insulin responses
      of different breeds of horses and ponies in moderate body condition to a glucose
      containing meal and to compare these responses with the indices of SI as
      determined by a frequently sampled intravenous glucose tolerance test (FSIGT).
      Eight Standardbred horses, 8 mixed-breed ponies, and 7 Andalusian-cross horses
      with a mean +/- SEM BCS 5.0 +/- 0.3 of 9 were used in this study. Each animal
      underwent an oral glucose tolerance test (OGTT) in which they were fed a fiber
      based ration (2.0 g/kg BW) containing 1.5 g/kg BW added glucose, as well as a
      standard FSIGT with minimal model analysis. The glucose response variables from
      the OGTT were similar between groups; however, the peak insulin concentration was
      higher in ponies (94.1 +/- 29.1 MUIU/mL; P = 0.003) and Andalusians (85.3 +/-
      18.6; P = 0.004) than in Standardbreds (21.2 +/- 3.5). The insulin area under the
      curve was also higher in ponies (13.5 +/- 3.6 IU . min . L(-1); P = 0.009) and
      Andalusians (15.0 +/- 2.7; P = 0.004) than in Standardbreds (3.1 +/- 0.6).
      Insulin sensitivity, as determined by the FSIGT, was lower in Andalusians (0.99
      +/- 0.18 * 10(-4)/[mIU . min]) than in Standardbreds (5.43 +/- 0.94; P < 0.001)
      and in ponies (2.12 +/- 0.44; P = 0.003) than in Standardbreds. Peak insulin
      concentrations from the OGTT were negatively correlated with SI (P < 0.001; rs = 
      0.75). These results indicate that there are clear breed-related differences in
      the insulin responses of horses and ponies to oral and intravenous glucose. All
      animals were in moderate body condition, indicating that breed-related
      differences in insulin dynamics occurred independent of obesity.

PMID- 24308929
TI  - Preface. Genomics, microbiomes, single cell analysis and next-generation
      sequencing.

PMID- 24308930
TI  - Epstein-Barr virus microRNAs in plasma as potential biomarkers for chronic
      infections: reply to Makarewicz et al.

PMID- 24308931
TI  - Prevention of Staphylococcus aureus infections by glycoprotein vaccines
      synthesized in Escherichia coli.
AB  - BACKGROUND: Staphylococcus aureus is a leading cause of superficial and invasive
      human disease that is often refractory to antimicrobial therapy. Vaccines have
      the potential to reduce the morbidity, mortality, and economic impact associated
      with staphylococcal infections. However, single-component vaccines targeting S.
      aureus have failed to show efficacy in clinical trials. METHODS: A novel
      glycoengineering technology for creation of a multicomponent staphylococcal
      vaccine is described. Genes encoding S. aureus capsular polysaccharide (CP)
      biosynthesis, PglB (a Campylobacter oligosaccharyl transferase), and a protein
      carrier (detoxified Pseudomonas aeruginosa exoprotein A or S. aureus alpha toxin
      [Hla]) were coexpressed in Escherichia coli. Recombinant proteins N-glycosylated
      with S. aureus serotype 5 or 8 CPs were purified from E. coli. RESULTS: Rabbits
      and mice immunized with the glycoprotein vaccines produced antibodies that were
      active in vitro in functional assays. Active and passive immunization strategies
      targeting the CPs protected mice against bacteremia, and vaccines targeting Hla
      protected against lethal pneumonia. The CP-Hla bioconjugate vaccine protected
      against both bacteremia and lethal pneumonia, providing broad-spectrum efficacy
      against staphylococcal invasive disease. CONCLUSIONS: Glycoengineering
      technology, whereby polysaccharide and protein antigens are enzymatically linked
      in a simple E. coli production system, has broad applicability for use in vaccine
      development against encapsulated microbial pathogens.

PMID- 24308932
TI  - Epstein-Barr Virus MicroRNAs in plasma as potential biomarkers for chronic
      infections: (response to: Kawano et al; The Journal of Infectious Diseases; 2013;
      208:771-9).

PMID- 24308933
TI  - DTREEv2, a computer-based support system for the risk assessment of genetically
      modified plants.
AB  - Risk assessment of genetically modified organisms (GMOs) remains a contentious
      area and a major factor influencing the adoption of agricultural biotech.
      Methodologically, in many countries, risk assessment is conducted by expert
      committees with little or no recourse to databases and expert systems that can
      facilitate the risk assessment process. In this paper we describe DTREEv2, a
      computer-based decision support system for the identification of hazards related
      to the introduction of GM-crops into the environment. DTREEv2 structures hazard
      identification and evaluation by means of an Event-Tree type of analysis. The
      system produces an output flagging identified hazards and potential risks. It is
      intended to be used for the preparation and evaluation of biosafety dossiers and,
      as such, its usefulness extends to researchers, risk assessors and regulators in
      government and industry. 

PMID- 24308934
TI  - Low-dose chronic lead exposure increases systolic arterial pressure and vascular
      reactivity of rat aortas.
AB  - Chronic lead exposure induces hypertension affecting endothelial function. We
      investigated whether low-concentration lead exposure alters blood pressure and
      vascular reactivity, focusing on the roles of NO, oxidative stress,
      cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin
      renin system. Aortic rings from 3-month-old Wistar rats were treated daily with
      lead acetate (first dose 4mg/100g, subsequent doses 0.05mg/100g, im) or vehicle
      for 30 days. Treatment increased lead blood levels (12MUg/dl), blood pressure,
      and aortic ring contractile response to phenylephrine (1nM-100mM). Contractile
      response after L-NAME administration increased in both groups but was higher
      after lead treatment. Lead effects on Rmax decreased more after apocynin and
      superoxide dismutase administration compared to control. Indomethacin reduced
      phenylephrine response more after lead treatment than in controls. The selective
      COX-2 inhibitor NS398, thromboxane A2/prostaglandin H2 receptor antagonist SQ
      29,548, TXA2 synthase inhibitor furegrelate, EP1 receptor antagonist SC 19220,
      and ACE inhibitor and AT1 receptor antagonist losartan reduced phenylephrine
      responses only in vessels from lead-treated rats. Basal and stimulated NO release
      was reduced and local O2(-) liberation increased in the lead-treated group
      compared to controls. eNOS, iNOS, and AT1 receptor protein expression increased
      with lead exposure, but COX-2 protein expression decreased. This is the first
      demonstration that blood Pb(2+) (12ug/dl) concentrations below the WHO
      established values increased systolic blood pressure and vascular phenylephrine
      reactivity. This effect was associated with reduced NO bioavailability, increased
      reactive oxygen species production, increased participation of COX-derived
      contractile prostanoids, and increased renin-angiotensin system activity. 

PMID- 24308935
TI  - Unacylated ghrelin promotes skeletal muscle regeneration following hindlimb
      ischemia via SOD-2-mediated miR-221/222 expression.
AB  - BACKGROUND: Surgical treatment of peripheral artery disease, even if successful,
      does not prevent reoccurrence. Under these conditions, increased oxidative stress
      is a crucial determinant of tissue damage. Given its reported antioxidant
      effects, we investigated the potential of unacylated-ghrelin (UnAG) to reduce
      ischemia-induced tissue damage in a mouse model of peripheral artery disease.
      METHODS AND RESULTS: We show that UnAG but not acylated ghrelin (AG) induces
      skeletal muscle regeneration in response to ischemia via canonical p38/mitogen
      actived protein kinase signaling UnAG protected against reactive oxygen species
      induced cell injuries by inducing the expression of superoxide dismutase-2 (SOD
      2) in satellite cells. This led to a reduced number of infiltrating CD68(+) cells
      and was followed by induction of the myogenic process and a reduction in
      functional impairment. Moreover, we found that miR-221/222, previously linked to
      muscle regeneration processes, was up-regulated and negatively correlated with
      p57(Kip2) expression in UnAG-treated mice. UnAG, unlike AG, promoted cell-cycle
      entry in satellite cells of mice lacking the genes for ghrelin and its receptor
      (GHSR1a). UnAG-induced p38/mitogen-actived protein kinase phosphorylation,
      leading to activation of the myogenic process, was prevented in SOD-2-depleted
      SCs. By siRNA technology, we also demonstrated that SOD-2 is the antioxidant
      enzyme involved in the control of miR-221/222-driven posttranscriptional
      p57(Kip2) regulation. Loss-of-function experiments targeting miR-221/222 and
      local pre-miR-221/222 injection in vivo confirmed a role for miR-221/222 in
      driving skeletal muscle regeneration after ischemia. CONCLUSIONS: These results
      indicate that UnAG-induced skeletal muscle regeneration after ischemia depends on
      SOD-2-induced miR-221/222 expression and highlight its clinical potential for the
      treatment of reactive oxygen species-mediated skeletal muscle damage.

PMID- 24308936
TI  - Mechanical dyssynchrony precedes QRS widening in ATP-sensitive K+ channel
      deficient dilated cardiomyopathy.
AB  - BACKGROUND: Contractile discordance exacerbates cardiac dysfunction, aggravating
      heart failure outcome. Dissecting the genesis of mechanical dyssynchrony would
      enable an early diagnosis before advanced disease. METHODS AND RESULTS: High
      resolution speckle-tracking echocardiography was applied in a knockout murine
      surrogate of adult-onset human cardiomyopathy caused by mutations in
      cardioprotective ATP-sensitive K(+) (K(ATP)) channels. Preceding the established
      criteria of cardiac dyssynchrony, multiparametric speckle-based strain resolved
      nascent erosion of dysfunctional regions within cardiomyopathic ventricles of the
      K(ATP) channel-null mutant exposed to hemodynamic stress. Not observed in wild
      type counterparts, intraventricular disparity in wall motion, validated by the
      degree, direction, and delay of myocardial speckle patterns, unmasked the disease
      substrate from asymptomatic to overt heart failure. Mechanical dyssynchrony
      preceded widening of the QRS complex and exercise intolerance and progressed into
      global myocardial discoordination and decompensated cardiac pump function,
      precipitating a low output syndrome. CONCLUSIONS: The present study, with the use
      of high-resolution imaging, prospectively resolved the origin and extent of
      intraventricular motion disparity in a K(ATP) channel-knockout model of dilated
      cardiomyopathy. Mechanical dyssynchrony established as an early marker of
      cardiomyopathic disease offers novel insight into the pathodynamics of
      dyssynchronous heart failure.

PMID- 24308937
TI  - Clinical and magnetic resonance imaging predictors of very early neurological
      response to intravenous thrombolysis in patients with middle cerebral artery
      occlusion.
AB  - BACKGROUND: The early identification of patients who are unlikely to respond to
      intravenous recombinant tissue plasminogen activator (IV-tPA) could help select
      candidates for additional intra-arterial therapy or add-on antithrombotic drugs
      during the acute stage of stroke. Given that very early neurological improvement
      (VENI) is a reliable surrogate of early recanalization, we assessed the clinical
      and magnetic resonance imaging predictors of lack of VENI. METHODS AND RESULTS:
      We reviewed consecutive ischemic stroke patients with middle cerebral artery
      occlusion and treated within 4.5 hours by IV-tPA between 2003 and 2012 in our
      center, where magnetic resonance imaging is systematically implemented as first
      line diagnostic workup. Lack of VENI was defined as a <40% decrease in baseline
      National Institutes of Health Stroke Scale (NIHSS) score 1 hour after start of IV
      tPA. Poor outcome was defined as a 3-month modified Rankin scale >=2.
      Associations between lack of VENI and potential determinants were assessed in
      logistic regression models. In all, 186 patients were included (median baseline
      NIHSS score, 16; median onset to treatment time, 155 minutes). One hundred forty
      three patients (77%) had no VENI. The variables significantly associated with
      lack of VENI in multivariable analysis were baseline NIHSS (OR, 1.08; 95% CI,
      1.01 to 1.16 per 1-point increase; P=0.03), onset to treatment time >120 minutes
      (OR, 2.94; 95% CI, 1.31 to 6.63; P=0.009) and diffusion weighted imaging--Alberta
      Stroke Programme Early CT Score <=5 (OR, 3.60; 95% CI, 1.14 to 11.35; P=0.03).
      Patients without VENI were more likely to have a modified Rankin Scale >=2 than
      those without VENI (68% versus 24%; OR, 5.01; 95% CI, 2.12 to 11.82) and less
      likely to have recanalization after 24 hours (OR, 0.41; 95% CI, 0.19 to 0.88).
      CONCLUSIONS: Lack of VENI provides an early estimate of 3-month outcome and
      recanalization after IV-tPA. Baseline NIHSS, onset to treatment time, and
      diffusion weighted imaging--Alberta Stroke Programme Early CT Score could help to
      predict lack of VENI and, in turn, might help early selection of candidates for
      complementary reperfusion strategies.

PMID- 24308938
TI  - A plasma long-chain acylcarnitine predicts cardiovascular mortality in incident
      dialysis patients.
AB  - BACKGROUND: The marked excess in cardiovascular mortality that results from
      uremia remains poorly understood. METHODS AND RESULTS: In 2 independent, nested
      case-control studies, we applied liquid chromatography-mass spectrometry-based
      metabolite profiling to plasma obtained from participants of a large cohort of
      incident hemodialysis patients. First, 100 individuals who died of a
      cardiovascular cause within 1 year of initiating hemodialysis (cases) were
      randomly selected along with 100 individuals who survived for at least 1 year
      (controls), matched for age, sex, and race. Four highly intercorrelated long
      chain acylcarnitines achieved the significance threshold adjusted for multiple
      testing (P<0.0003). Oleoylcarnitine, the long-chain acylcarnitine with the
      strongest association with cardiovascular mortality in unadjusted analysis,
      remained associated with 1-year cardiovascular death after multivariable
      adjustment (odds ratio per SD 2.3 [95% confidence interval, 1.4 to 3.8];
      P=0.001). The association between oleoylcarnitine and 1-year cardiovascular death
      was then replicated in an independent sample (n=300, odds ratio per SD 1.4 [95%
      confidence interval, 1.1 to 1.9]; P=0.008). Addition of oleoylcarnitine to
      clinical variables improved cardiovascular risk prediction using net
      reclassification (NRI, 0.38 [95% confidence interval, 0.20 to 0.56]; P<0.0001).
      In physiologic profiling studies, we demonstrate that the fold change in plasma
      acylcarnitine levels from the aorta to renal vein and from pre- to
      posthemodialysis samples exclude renal or dialytic clearance of long-chain
      acylcarnitines as confounders in our analysis. CONCLUSIONS: Our data highlight
      clinically meaningful alterations in acylcarnitine homeostasis at the time of
      dialysis initiation, which may represent an early marker, effector, or both of
      uremic cardiovascular risk.

PMID- 24308939
TI  - Regulation of angiopoietin-1/Tie-2 receptor signaling in endothelial cells by
      dual-specificity phosphatases 1, 4, and 5.
AB  - BACKGROUND: Angiopoietin-1 (Ang-1) promotes survival and migration of endothelial
      cells, in part through the activation of mitogen-activated protein kinase (MAPK)
      pathways downstream of Tie-2 receptors. Dual-specificity phosphatases (DUSPs)
      dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine residues on
      target MAPKs. The mechanisms by which DUSPs modulate MAPK activation in Ang-1/Tie
      2 receptor signaling are unknown in endothelial cells. METHODS AND RESULTS:
      Expression of various DUSPs in human umbilical vein endothelial cells exposed to
      Ang-1 was measured. The functional roles of DUSPs in Ang-1-induced regulation of
      MAPK activation, endothelial cell survival, migration, differentiation, and
      permeability were measured using selective siRNA oligos. Ang-1 differentially
      induces DUSP1, DUSP4, and DUSP5 in human umbilical vein endothelial cells through
      activation of the PI-3 kinase, ERK1/2, p38, and SAPK/JNK pathways. Lack-of
      function siRNA screening revealed that DUSP1 preferentially dephosphorylates p38
      protein and is involved in Ang-1-induced cell migration and differentiation.
      DUSP4 preferentially dephosphorylates ERK1/2, p38, and SAPK/JNK proteins and,
      under conditions of serum deprivation, is involved in Ang-1-induced cell
      migration, several antiapoptotic effects, and differentiation. DUSP5
      preferentially dephosphorylates ERK1/2 proteins and is involved in cell survival
      and inhibition of permeability. CONCLUSIONS: DUSP1, DUSP4, and DUSP5
      differentially modulate MAPK signaling pathways downstream of Tie-2 receptors,
      thus highlighting the importance of these phosphatases to Ang-1-induced
      angiogenesis.

PMID- 24308940
TI  - Finite element analysis of thermal laser skin stimulation for a finer
      characterization of the nociceptive system.
AB  - Thermal laser stimulation of the skin is an efficient exploratory tool to
      characterize the nociceptive system. In the present study, finite element
      simulations are done to calculate the intra-cutaneous spatio-temporal temperature
      profiles following the delivery of such laser stimuli. The proposed computer
      aided modeling considers a number of important parameters that have been
      disregarded in previous approaches: (i) variability of water content across the
      skin in both hairy and glabrous skin, (ii) temperature dependency of optical and
      thermal skin parameters, (iii) laser wavelength and corresponding absorption
      coefficient, (iv) beam shape (Gaussian vs. flat top) and (v) power emission
      (closed vs. open loop). Numerical simulations allow determining at each instant
      of time the volume and area of skin tissue whose temperature exceeds a given
      nociceptor activation threshold. This knowledge allows a finer characterization
      of the subpopulations of primary afferents that encode and convey nociceptive
      signals to the central nervous system. As an example, the approach is used to
      obtain an estimate of intraepidermal nerve fiber density in both physiological
      and pathological conditions. Moreover, a better knowledge of the heat
      distribution also reduces the risk of injury to the skin. Finally, in order to
      make the finite element simulations accessible to investigators with no prior
      background in numerical analysis, a specific open-source user-interface has been
      developed with the ONELAB software. 

PMID- 24308941
TI  - [Indications for magnetic resonance imaging for low back pain in adults].
AB  - INTRODUCTION: Low back pain is a common disorder that generates many medical
      consultations. Magnetic Resonance Imaging (MRI) is commonly used in the clinical
      management of some of these patients. However, the cost of inappropriate MRI use
      is high, so there is a need to develop guidelines to help physicians make correct
      decisions and optimize available resources. OBJECTIVE: To determine the main
      clinical indications for MRI scanning in adults with low back pain. MATERIAL AND
      METHODS: The RAND/UCLA appropriateness method was used: After a systematic review
      (May 2012), a list of the clinical indications for MRI scanning in patients with
      low back pain was prepared. A multidisciplinary expert panel scored each
      indication from 1, "totally inappropriate" to 9, "totally appropriate". A first
      on-line round, an in-person panel meeting, where results of the first round were
      discussed, and a final second on-line round were arranged. A clinical indication
      was considered appropriate if the median score was 6.5 or higher, and there was
      agreement between experts (IPRAS index was used). RESULTS: An MRI test is
      considered appropriate if cancer, spinal infection or a fracture, even with a
      negative X-ray test is suspected.; if there is inflammatory back pain;
      severe/progressive neurological deficit; severe and progressive low back pain;
      subacute or chronic low back pain with radicular involvement unresponsive to
      conservative therapy. CONCLUSIONS: Clinical indications for a MRI scanning are
      based on the suspicion of a secondary serious pathology. This methodology helps
      to set clinical indications for MRI, and may be of great value for both
      clinicians and health managers.

PMID- 24308942
TI  - Letter to the Editor on "Muscle function during gait is invariant to age when
      walking speed is controlled" by Lim YP, Lin YC, Pandy MG, Gait Posture
      2013;38(2):253-9.

PMID- 24308943
TI  - Antimicrobial and antioxidant effects of spice extracts on the shelf life
      extension of raw chicken meat.
AB  - The antimicrobial and antioxidant effects of different spice extracts in raw
      chicken meat during storage for 15 days at 4  degrees C were studied. Raw chicken
      meat was treated with BHT (positive control), Syzygium aromaticum (SA), Cinnmomum
      cassia (CC), Origanum vulgare (OV), and Brassica nigra (BN) extracts and the
      different combinations as well as the results were compared to raw chicken meat
      without any additive (negative control). The antioxidant and antimicrobial
      activities of spice extracts were determined. Total phenolic contents and
      flavonoid contents were ranged from 14.09 +/- 0.78 to 24.65 +/- 0.83 mg of GAE/g
      and 7.07 +/- 0.15 to 12.13 +/- 0.24 mg of quercetin/g, respectively. The pH,
      instrumental color (CIE L*, a*, b*), total viable counts (TVC), Lactic Acid
      Bacteria (LAB) counts, Enterobacteriaceae counts, Pseudomonas spp. counts and 2
      thiobarbituric acid reactive substances (TBARS) were determined at a gap of 3
      days interval for a period of 15 days. The bacterial counts of T-W-SA+T-W-CC+T-W
      OV samples were lower than control samples during storage. T-W-SA+T-W-CC+T-W-OV
      samples maintained significantly (P<0.05) higher L*, a* and b* values while
      storing. The TBARS values of T-W-SA+T-W-CC+T-W-OV samples were lowest among the
      samples. These results show that spice extracts are very effective against
      microbial growth, lipid oxidation and has potential as a natural antioxidant in
      raw chicken meats.

PMID- 24308944
TI  - Metabolic changes of starch and lipid triggered by nitrogen starvation in the
      microalga Chlorella zofingiensis.
AB  - The aim of this research was to study the metabolic changes of starch and lipid
      biosynthesis in the microalga Chlorella zofingiensis under nitrogen starvation in
      comparison to nitrogen abundant condition. C. zonfingiensis showed a rapid growth
      and kept stable chlorophyll content when grown in nitrogen-replete medium, while
      a severe inhibition of cell growth and a sharp degradation of chlorophyll
      occurred under nitrogen depletion. Nitrogen-replete C. zonfingiensis cells
      possessed basal levels of starch and lipid. Upon nitrogen starvation, both starch
      and lipid increased greatly within cells, but starch synthesis preceded lipid
      accumulation. After 2 days of stress condition, starch was partially degraded,
      possibly to support lipid synthesis. It was speculated that starch accumulation
      acted as a quick response to environmental stress, whereas lipid served as long
      term energy storage. Additionally, C. zonfingiensis tends to lower the degree of
      unsaturation in response to nitrogen starvation which is desirable for biodiesel
      production.

PMID- 24308946
TI  - Analysis of the duration of migraine prophylaxis.
AB  - To determine the minimum duration of migraine prophylaxis, after patients become
      pain-free. Migraine patients diagnosed according to criteria of International
      Classification of Headache Disorders-2 were treated prophylactically. After
      becoming pain-free, they were divided into two equal groups: in group 1,
      prophylaxis was maintained for another 12 months and in group 2, for 24 months.
      Each group was followed for more three years after prophylaxis period. Of the 50
      patients, 39 (78%) were female and 11 (22%) were male. The age ranged from 18 to
      50 years. Before treatment, the attack frequency for groups 1 and 2 was,
      respectively, 16.3 +/- 12.8 and 16.4 +/- 11.8 days per month (p = 0.769).
      Patients in groups 1 and 2 have become pain-free, respectively, with 21.4 +/-
      11.2 and 16.8 +/- 9.9 months (p = 0.161). During three years without treatment,
      groups 1 and 2 maintained an annual frequency of respectively 3.2 and 0.5
      headache days. Of the patients in group 2, 76.0% (19/25) remained pain-free
      during follow-up, versus 44.0% (11/25) of group 1, with a significant difference
      (p=0.001). The best results were obtained when migraine prophylaxis was
      maintained for 24 months after patients became pain-free.

PMID- 24308945
TI  - Analysis of CYP27B1 in multiple sclerosis.
AB  - The analysis of genetic variability in CYP27B1 and its effect on risk of multiple
      sclerosis (MS) has yielded conflicting results. Here we describe a study to
      genetically characterize CYP27B1 and elucidate its role on MS risk in the
      Canadian population. Sequencing CYP27B1 failed to identify mutations known to
      cause loss of enzymatic activity, however genotyping of p.R389H in cases and
      controls identified the mutation in one multi-incident family (allele
      frequency=0.03%) in which the p.R389H mutation segregates with disease in five
      family members diagnosed with MS, thus providing additional support for CYP27B1
      p.R389H in the pathogenicity of MS. 

PMID- 24308947
TI  - The antithrombotic effect of dabigatran.

PMID- 24308949
TI  - Autonomic function is not associated with the incidence of type 2 diabetes in a
      high-risk population: the Hoorn study.
AB  - AIM: Impaired autonomic function is a complication of type 2 diabetes mellitus
      (DM2), but may also be involved in its development. For this reason, this study
      looked at the association of autonomic function with the incidence of DM2 in a
      homogeneous Caucasian population. METHODS: This Hoorn study was a prospective
      population-based study of individuals aged 50-75 years. For the 631 participants,
      the standard deviation of all normal-to-normal intervals (SDNN) and eight other
      parameters of autonomic function were calculated at baseline. Fasting and 2-h
      glucose were measured during follow-up by oral glucose tolerance test (OGTT). DM2
      at baseline and follow-up was ascertained by questionnaire and OGTT. After
      excluding participants with DM2 at baseline, the association of parameters of
      autonomic function with incident diabetes was examined using logistic-regression
      analysis while adjusting for possible confounders. RESULTS: After excluding those
      with known (n=67) or newly diagnosed (n=126) DM2 at baseline and those missing
      follow-up data (n=140), 298 participants were eligible for the study (182 with
      normal glucose tolerance, 19 with impaired fasting glucose and 97 with impaired
      glucose tolerance). During a median follow-up of 9.2 (range 4.5-11.1) years, 94
      incident cases of DM2 were observed. After adjusting for confounding variables,
      the DM2 odds ratio was 1.12 (95% CI: 0.77, 1.64) per SDNN increase. Results for
      other parameters of autonomic function were similar. CONCLUSION: The present
      study found no evidence of an association between autonomic function and DM2
      incidence in a population at high risk of diabetes. This implies that previously
      observed associations between autonomic function and glucose metabolism in cross
      sectional settings may reflect reverse causation.

PMID- 24308948
TI  - Surface behavior of apolipoprotein A-I and its deletion mutants at model
      lipoprotein interfaces.
AB  - Apolipoprotein A-I (apoA-I) has a great conformational flexibility to exist in
      lipid-free, lipid-poor, and lipid-bound states during lipid metabolism. To
      address the lipid binding and the dynamic desorption behavior of apoA-I at
      lipoprotein surfaces, apoA-I, Delta(185-243)apoA-I, and Delta(1-59)(185-243)apoA
      I were studied at triolein/water and phosphatidylcholine/triolein/water
      interfaces with special attention to surface pressure. All three proteins are
      surface active to both interfaces lowering the interfacial tension and thus
      increasing the surface pressure to modify the interfaces. Delta(185-243)apoA-I
      adsorbs much more slowly and lowers the interfacial tension less than full-length
      apoA-I, confirming that the C-terminal domain (residues 185-243) initiates the
      lipid binding. Delta(1-59)(185-243)apoA-I binds more rapidly and lowers the
      interfacial tension more than Delta(185-243)apoA-I, suggesting that destabilizing
      the N-terminal alpha-helical bundle (residues 1-185) restores lipid binding. The
      three proteins desorb from both interfaces at different surface pressures
      revealing that different domains of apoA-I possess different lipid affinity.
      Delta(1-59)(185-243)apoA-I desorbs at lower pressures compared with apoA-I and
      Delta(185-243)apoA-I indicating that it is missing a strong lipid association
      motif. We propose that during lipoprotein remodeling, surface pressure mediates
      the adsorption and partial or full desorption of apoA-I allowing it to exchange
      among different lipoproteins and adopt various conformations to facilitate its
      multiple functions. 

PMID- 24308950
TI  - Reduced trabecular bone mass and strength in mice overexpressing Galpha11 protein
      in cells of the osteoblast lineage.
AB  - G protein-coupled receptors (GPCRs) require G proteins for intracellular
      signaling to regulate a variety of growth and maintenance processes, including
      osteogenesis and bone turnover. Bone maintenance events may be altered by changes
      in the activity or level of G proteins, which then modify signaling in bone cells
      such as osteoblasts. We have previously reported increased levels of Galpha11
      protein and signaling to phospholipase C/protein kinase C pathways in response to
      dexamethasone in osteoblastic UMR 106-01 cells. Here we generated pOBCol3.6-GNA11
      transgenic mice that overexpress Galpha11 protein in cells of the osteoblast
      lineage (G11-Tg mice). G11-Tg mice exhibit an osteopenic phenotype characterized
      by significant reductions in trabecular bone mineral density, thickness, number
      and strength. The numbers of osteoblasts and osteocytes were unchanged in G11-Tg
      bone, but early markers of osteoblast differentiation, Alp and Bsp, were
      increased while the late stage differentiation marker Ocn was not changed
      suggesting reduced osteoblast maturation in G11-Tg trabecular bone which was
      accompanied by a decreased bone formation rate. Furthermore, in vitro cultures of
      G11-Tg primary osteoblasts show delayed osteoblast differentiation and
      mineralization. Histological analyses also revealed increased osteoclast
      parameters, accompanied by elevated mRNA expression of Trap and Ctsk. mRNA levels
      of Rankl and M-csf were elevated in vitro in bone marrow stromal cells undergoing
      osteogenesis and in trabecular bone in vivo. Together, these findings demonstrate
      that increasing Galpha11 protein expression in osteoblasts can alter gene
      expression and result in a dual mechanism of trabecular bone loss. 

PMID- 24308951
TI  - Transsphenoidal removal of intrasellar pilocytic astrocytoma.
AB  - A 26-year-old man with a sellar pilocytic astrocytoma had a recurrent non
      enhancing mass located in the sellar/suprasellar region visible on MRI. Due to
      tumor progression and worsening vision, the mass was completely resected through
      a transsphenoidal approach. Postoperatively, the patient's vision improved and
      imaging showed complete removal of the tumor and optic pathway decompression.
      Pilocytic astrocytomas originating in suprasellar structures can intrude into the
      sella, and should be included in the differential diagnosis of intrasellar
      tumors. The transsphenoidal approach can be effective for resecting such tumors. 

PMID- 24308952
TI  - Bow hunter's syndrome unmasked after contralateral vertebral artery sacrifice for
      aneurysmal subarachnoid hemorrhage.
AB  - Bow hunter's syndrome (BHS), or positional vertebrobasilar insufficiency, is a
      rare disorder characterized by positional stenosis or occlusion of the dominant
      vertebral artery (VA) with concordant signs and symptoms of brainstem ischemia.
      Many etiologies have been described, with the most common level of obstruction
      occurring at the craniocervical junction. The authors report acquired BHS after
      the patient's contralateral VA was sacrificed for ruptured aneurysm. A 44-year
      old man was referred to our institution for years of continued positional
      tinnitus, vertigo, and nausea. This symptomatology began 5 years prior,
      immediately after the patient's right VA was endovascularly sacrificed to treat a
      ruptured VA aneurysm. From the time of treatment, right head turning caused
      instantaneous symptoms consistent with brainstem ischemia. Evaluations performed
      during the 5 year interim before referral included computed tomography
      angiography, MRI, and diagnostic cerebral angiography (DCA). All failed to
      identify a causal etiology. A diagnosis of BHS was made with dynamic DCA. With
      the patient's head turned to the right, angiography of the left VA demonstrated a
      positional block. The patient underwent left VA decompression. Intraoperative
      dynamic DCA was utilized to demonstrate adequacy of decompression. The patient
      tolerated the procedure without complication. Symptomatology immediately
      completely subsided and remained absent at his 3 month follow-up. An acquired BHS
      should be recognized as a possible complication if VA sacrifice is considered for
      an unclippable or uncoilable aneurysm.

PMID- 24308953
TI  - Extended endoscopic endonasal approach for suprasellar Rathke's cleft cysts.
AB  - Purely suprasellar Rathke's cleft cysts (RCC) treated with a microscopic
      endonasal approach have increased operative morbidity and poorer outcomes
      compared to purely sellar RCC. We sought to determine if the extended endoscopic
      endonasal approach improved outcomes for suprasellar RCC. We retrospectively
      reviewed RCC patients at our institution over a 10 year period comparing outcomes
      of purely sellar RCC treated microsurgically (n=68), purely suprasellar RCC
      treated microsurgically (n=22), and purely suprasellar RCC treated endoscopically
      (n=9). Suprasellar RCC treated endoscopically were similar in size to those
      treated microscopically (0.9 versus 1.1cm; p=0.4). Complete cyst drainage
      occurred in 78% of suprasellar RCC approached endoscopically versus 25%
      approached microsurgically (p=0.02), approaching the 84% complete drainage rate
      seen with sellar microsurgically approached RCC. Visual normalization occurred in
      67% of suprasellar RCC patients treated endoscopically versus 29% treated
      microsurgically (p=0.5). Headache improved in 71% of suprasellar RCC treated
      endoscopically, more than the 33% of suprasellar RCC treated microsurgically and
      the 53% of sellar RCC treated microsurgically (p=0.4). Diabetes insipidus (all
      temporary) occurred in 22% of patients with suprasellar RCC treated
      endoscopically, slightly greater than the 14% in suprasellar microsurgical
      patients and 9% in sellar RCC treated microsurgically (p>0.05). Cerebrospinal
      fluid (CSF) leak did not occur in any of the suprasellar RCC treated
      endoscopically, while 14% treated microsurgically experienced a CSF leak
      (p>0.05). Suprasellar RCC are neurosurgically challenging due to their proximity
      to the optic chiasm and infundibulum. Compared to microsurgery, endoscopy
      improves rate of complete removal and visual outcomes.

PMID- 24308954
TI  - Assessment of neurological clinical management reasoning in medical students.
AB  - In neurology education there is evidence that trainees may have greater ability
      in general localization and diagnosis than they do in treatment decisions,
      particularly with considering longer term care and supportive care. We
      hypothesized that medical students completing a neurology clerkship would exhibit
      greater skill at considering the acute diagnostic and therapeutic management than
      at considering supportive management measures. Data from 720 standardized patient
      encounters by 360 medical students completing a neurology clerkship being
      evaluated via an objective structured clinical examination were analyzed for
      skill in three components of clinical decision making: diagnostic evaluation,
      therapeutic intervention, and supportive intervention. Scores for all
      standardized patient encounters over the 2008-2012 interval revealed a
      significantly higher percentage of correct responses in both the diagnostic (mean
      [M]=62.6%, standard deviation [SD]=20.3%) and therapeutic (M=63.0%, SD=28.8%)
      categories in comparison to the supportive (M=31.8%, SD=45.2%) category. However,
      only scores in therapeutic and supportive treatment plans were found to be
      significant predictors of the USA National Board of Medical Examiners (NBME)
      clinical neurology subject examination scores; on average, a percent increase in
      therapeutic and support scores led to 5 and 2 point increases in NBME scores,
      respectively. We demonstrate empirical evidence of deficits in a specific
      component of clinical reasoning in medical students at the completion of a
      neurology clerkship. 

PMID- 24308955
TI  - Familial colloid cyst.
AB  - Colloid cysts of the third ventricle are rare benign tumours that can present as
      symptomatic hydrocephalus or be an incidental finding on imaging. This report
      presents familial colloid cysts found in a mother and daughter. Prior examples of
      familial colloid cysts are also reviewed and suggestions regarding the mode of
      inheritance and screening strategy are proposed. 

PMID- 24308956
TI  - I endeavor to make it: effort increases valuation of subsequent monetary reward.
AB  - Although it is commonly accepted that the amount of effort we put into
      accomplishing a task would exert an influence on subsequent reward processing and
      outcome evaluation, whether effort is incorporated as a cost or it would increase
      the valuation of concomitant reward is still under debate. In this study, EEGs
      were recorded while subjects performed calculation tasks that required different
      amount of effort, correct responses of which were followed by either no reward or
      fixed compensation. Results showed that high effort induced larger differentiated
      FRN responses to the reward and non-reward discrepancy across two experimental
      conditions. Furthermore, P300 manifested valence effect during reward feedback,
      with more positive amplitudes for reward than for non-reward only in the high
      effort condition. These results suggest that effort might increase subjective
      evaluation toward subsequent reward. 

PMID- 24308957
TI  - Inhibition of the glucocorticoid synthesis reverses stress-induced decrease in
      rat's 50-kHz ultrasonic vocalizations.
AB  - The playful, experimenter-administered manual somatosensory stimulation of rats
      results in a positive affect that triggers emission of ~50-kHz ultrasonic
      vocalizations (USVs), which have been proposed to index positive emotions akin to
      human joy and laughter. Our earlier findings showed that restraint stress
      decreased rat's tendency to emit 50-kHz USVs. Here we investigated whether the
      effects of stress on "tickling"-induced vocalizations could be alleviated by the
      glucocorticoid synthesis inhibitor, metyrapone. After the daily tickling sessions
      carried out until the USV response to tickling has stabilized, the rats were
      subjected to either handling, handling and metyrapone treatment, restraint stress
      lasting one week or the restraint stress and metyrapone treatment. Our results
      confirmed that animals exposed to restraint stress diminish the number of
      "tickling"-induced vocalizations as compared to the "tickled" but handled
      conspecifics. Metyrapone treatment prevented this effect in stressed animals
      having no effects in handled rats. The off-line analysis revealed that the
      majority (82-88%) of "tickling"-induced USVs were of the 50-kHz frequency
      modulated type and that the flat USVs appeared much less frequently (8.5-12%)
      while the 22-kHz alarm calls appeared sporadically (0.3-8%). Moreover, the
      acoustic parameters of the 50-kHz frequency modulated and flat USVs resembled the
      calls described earlier in adult rats. The results of the present study offer a
      way of identifying anti-stress and perhaps anti-depressant action of novel
      compounds based on the measurement of a positive affect of animals.

PMID- 24308958
TI  - Mobility of Po and U-isotopes under acid mine drainage conditions: an
      experimental approach with samples from Rio Tinto area (SW Spain).
AB  - Under acid mine drainage (AMD) conditions, the solubilities and mobilities of
      many elements are vastly different from conditions prevailing in most natural
      waters. Studies are underway in the Rio Tinto area (Iberian Pyrite Belt), in
      order to understand the behavior and mobility of long-lived U-series
      radionuclides under AMD conditions. A set of leaching experiments utilizing
      typical country rocks from the Tinto River basin, waste rock pile composite
      materials, iron-rich riverbed sediments and gossan (weathered naturally rock)
      were performed towards this purpose. Initial leaching experiments using distilled
      water kept in contact with solid material for 300, 100, 50 and 1 h resulted in
      very low concentrations of U with (234)U/(238)U activity ratios close to
      equilibrium and activity concentrations of (210)Po < 0.03 mBq/g. Leaching
      experiments performed with sulfuric acid media (0.1 and 0.01 M), and contact
      times between the solid and solution for 24 h were conducted to quantify the
      amount of U-isotopes and (210)Po leached, and the radioactive disequilibria
      generated between the radionuclides in the leachate. These experiments show that
      Po mobility in acidic conditions (pH around 1-2) is very low, with (210)Po
      activity in the leachate to be 6% in average for the solid sample. By contrast,
      mobility of U-isotopes is higher than that of Po, around 1.2%. 

PMID- 24308959
TI  - Antigenic peptide nanofibers elicit adjuvant-free CD8+ T cell responses.
AB  - Vaccines that elicit robust CD8+ T cell responses are desirable for protection
      against infectious diseases and cancers. However, most vaccine adjuvants fail to
      elicit robust CD8+ T cell responses without inflammation and associated toxicity.
      We recently reported that self-assembling peptides that form nanofibers in
      physiological buffers elicited strong adjuvant-free and antigen-specific antibody
      responses in mice. However, whether or not such nanofibers likewise can elicit
      strong CD8+ T cell responses is unknown. Here, we demonstrate that the self
      assembling peptide Q11 conjugated to a CD8+ T cell epitope of ovalbumin (Q11
      OVA), elicits strong antigen-specific primary and recall responses, and in a
      vaccination regimen protects against subsequent infection. Importantly, we show
      that these antigenic peptide nanofibers do not persist as an inflammatory antigen
      depot at the injection site. Our results demonstrate for the first time that self
      assembling peptides may be useful as carriers for vaccines where CD8+ T cell
      mediated protection is needed.

PMID- 24308960
TI  - Tetanus, diphtheria and acellular pertussis (Tdap) vaccination among healthcare
      personnel-United States, 2011.
AB  - BACKGROUND: Health-care personnel (HCP) are at risk for exposure to and possible
      transmission of vaccine-preventable diseases. Receiving recommended vaccines is
      an essential prevention practice for HCP to protect themselves and their
      patients. The tetanus, diphtheria and acellular pertussis vaccine (Tdap) was
      recommended by the Advisory Committee on Immunization Practices (ACIP) for HCP in
      2006 for protection against pertussis. We assessed the recent compliance of U.S.
      HCP in receiving Tdap vaccination. METHODS: To estimate Tdap vaccination coverage
      among HCP, we analyzed data from the 2011 National Health Interview Survey
      (NHIS). Multivariable logistic regression and predictive marginal models were
      performed to identify factors independently associated with vaccination among
      HCP. RESULTS: Overall, Tdap vaccination coverage was 26.9% among HCP aged 18-64
      years (95% confidence interval (CI)=24.3%, 29.7%), which was significantly higher
      compared with non-HCP among the same age group (11.1%; 10.5-11.8%). Overall,
      vaccination coverage was significantly higher among physicians (41.5%) compared
      with nurses (36.5%) and other types of HCP (range 11.7-29.9%). Vaccination
      coverage was significantly higher among HCP aged 18-49 years compared with those
      50-64 years (30.0% vs. 19.2%, respectively). Characteristics independently
      associated with an increased likelihood of Tdap vaccination among HCP were:
      younger age, higher education, living in the western United States, being
      hospitalized within past year, having a place for routine health care in clinic
      or health center, and receipt of influenza vaccination in the previous year.
      Marital status of widowed, divorced, or separated was independently associated
      with a decreased likelihood of Tdap vaccination among HCP. CONCLUSIONS: By 2011,
      Tdap vaccination coverage was only 26.9% among HCP. Vaccination coverage varied
      widely by types of HCP and demographic characteristics. Emphasizing the benefits
      of HCP vaccination for staff and patients, providing vaccinations in the
      workplace and other non-traditional settings, and providing Tdap at no charge may
      help increase Tdap vaccination among HCP in all health-care settings.

PMID- 24308961
TI  - FOXP3 inhibits NF-kappaB activity and hence COX2 expression in gastric cancer
      cells.
AB  - Gastric cancer remains the main cause of cancer related deaths all over the
      world, and upregulated COX2 is a key player in its development. The mechanism as
      to how COX2 is regulated during the gastric cancer development is largely
      unknown. In this study, we found that the expression of COX2 was closely
      correlated with NF-kappaB activity. Strikingly, NF-kappaB activity was not
      absolutely consistent with its nuclear localization. Especially, in some cancer
      cell lines, such as MKN28, there were abundant nuclear localized NF-kappaB, while
      NF-kappaB luciferase activity in this cell line was relatively low. Furthermore,
      FOXP3 was found to be abundantly expressed in these cells. When the nuclear
      localized NF-kappaB expression was adjusted with the expression of FOXP3, it then
      correlated well with NF-kappaB activity. Molecularly, increased FOXP3 expression
      can interact with NF-kappaB and thus repress its activity. Knockdown of FOXP3
      could increase NF-kappaB activity, COX2 expression, and cell migration. Taken
      together, our study revealed that function of FOXP3 as a negative regulator of NF
      kappaB activity and thus plays a tumor suppressor role by reducing cell
      metastasis. 

PMID- 24308962
TI  - HDAC6 mediates the acetylation of TRIM50.
AB  - The E3 Ubiquitin ligase TRIM50 promotes the formation and clearance of aggresome
      associated polyubiquitinated proteins through HDAC6 interaction, a tubulin
      specific deacetylase that regulates microtubule-dependent aggresome formation. In
      this report we showed that TRIM50 is a target of HDAC6 with Lys-372 as a critical
      residue for acetylation. We identified p300 and PCAF as two TRIM50
      acetyltransferases and we further showed that a balance between ubiquitination
      and acetylation regulates TRIM50 degradation. 

PMID- 24308963
TI  - Wnt signaling in adult intestinal stem cells and cancer.
AB  - Signaling initiated by secreted glycoproteins of the Wnt family regulates many
      aspects of embryonic development and it is involved in homeostasis of adult
      tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self
      renewal capacity of epithelial stem cells. The stem cell attributes are conferred
      by mutual interactions of the stem cell with its local microenvironment, the stem
      cell niche. The niche ensures that the threshold of Wnt signaling in the stem
      cell is kept in physiological range. In addition, the Wnt pathway involves
      various feedback loops that balance the opposing processes of cell proliferation
      and differentiation. Today, we have compelling evidence that mutations causing
      aberrant activation of the Wnt pathway promote expansion of undifferentiated
      progenitors and lead to cancer. The review summarizes recent advances in
      characterization of adult epithelial stem cells in the gut. We mainly focus on
      discoveries related to molecular mechanisms regulating the output of the Wnt
      pathway. Moreover, we present novel experimental approaches utilized to
      investigate the epithelial cell signaling circuitry in vivo and in vitro. Pivotal
      aspects of tissue homeostasis are often deduced from studies of tumor cells;
      therefore, we also discuss some latest results gleaned from the deep genome
      sequencing studies of human carcinomas of the colon and rectum. 

PMID- 24308964
TI  - HDAC4 protects cells from ER stress induced apoptosis through interaction with
      ATF4.
AB  - Histone deacetylase 4 (HDAC4) is involved in the regulation of many fundamental
      cell processes such as proliferation, differentiation, and survival via the
      modification of their substrates or protein-protein interactions. In this study,
      we found that HDAC4 could be upregulated under ER stress. There exists a direct
      interaction between HDAC4 and activating transcription factor 4 (ATF4). In vitro,
      overexpression of HDAC4 caused the retention of ATF4 in cytoplasm and inhibition
      of ATF4 transcriptional activity. ER stress could promote cell apoptosis through
      the upregulation of ATF4 levels and its target genes such as CHOP and TRB3. This
      effect was exacerbated by downregulation of HDAC4 levels. These results
      demonstrated that HDAC4 played an important role in the regulation of ER stress
      induced apoptosis through interacting with ATF4 and inhibiting its
      transcriptional activity. 

PMID- 24308965
TI  - HSP27 phosphorylation modulates TRAIL-induced activation of Src-Akt/ERK signaling
      through interaction with beta-arrestin2.
AB  - Heat shock protein 27 (HSP27) regulates critical cellular functions such as
      development, differentiation, cell growth and apoptosis. A variety of stimuli
      induce the phosphorylation of HSP27, which affects its cellular functions.
      However, most previous studies focused on the role of HSP27 protein itself in
      apoptosis, the particular role of its phosphorylation state in signaling
      transduction remains largely unclear. In the present study, we reported that
      HSP27 phosphorylation modulated TRAIL-triggered pro-survival signaling
      transduction. In HeLa cells, suppression of HSP27 phosphorylation by specific
      inhibitor KRIBB3 or MAPKAPK2 (MK2) knockdown and by overexpression of non
      phosphorylatable HSP27(3A) mutant demonstrated that hindered HSP27
      phosphorylation enhanced the TRAIL-induced apoptosis. In addition, reduced HSP27
      phosphorylation by KRIBB3 treatment or MK2 knockdown attenuated the TRAIL-induced
      activation of Akt and ERK survival signaling through suppressing the
      phosphorylation of Src. By overexpression of HSP27(15A) or HSP27(78/82A)
      phosphorylation mutant, we further showed that phosphorylation of HSP27 at serine
      78/82 residues was essential to TRAIL-triggered Src-Akt/ERK signaling
      transduction. Co-immunoprecipitation and confocal microscopy showed that HSP27
      interacted with Src and scaffolding protein beta-arrestin2 in response of TRAIL
      stimulation and suppression of HSP27 phosphorylation apparently disrupted the
      TRAIL-induced interaction of HSP27 and Src or interaction of HSP27 and beta
      arrestin2. We further demonstrated that beta-arrestin2 mediated HSP27 action on
      TRAIL-induced Src activation, which was achieved by recruiting signaling complex
      of HSP27/beta-arrestin2/Src in response to TRAIL. Taken together, our study
      revealed that HSP27 phosphorylation modulates TRAIL-triggered activation of Src
      Akt/ERK pro-survival signaling via interacting with beta-arrestin2 in HeLa cells.

PMID- 24308966
TI  - High glucose driven expression of pro-inflammatory cytokine and chemokine genes
      in lymphocytes: molecular mechanisms of IL-17 family gene expression.
AB  - High glucose is an independent risk factor that alters the expression pattern of
      cytokines/chemokine leading to leukocyte activation in diabetes. Fluctuation of
      cytokine milieu in lymphocytes may lead to differentiation into a particular
      subset. Our objectives were to profile high glucose induced inflammatory gene
      expression in lymphocytes, to examine in vivo relevance in diabetes and to
      identify the key transcription factors and signaling pathways involved. Cytokine
      gene arrays and T-helper (Th1/Th2/Th17) cytokine profiler RT(2)-PCR arrays used
      for cytokine expression profiling followed by validation using Real Time-qPCR and
      relative RT-PCR in Jurkat T-lymphocytes, peripheral blood lymphocytes (PBLCs)
      from normal and diabetes subjects. Luciferase reporter plasmid, pharmacological
      inhibitors and mutant plasmids were used for promoter activation and signaling
      pathway studies. High glucose induced gene profiling in Jurkat T-lymphocytes
      showed significantly increased expression of 64 proinflammatory genes including
      IL-6 and IL-17A and most of these genes were Nuclear Factor (NF)-kappaB and AP-1
      regulated. RT(2)-PCR array results suggested the transcriptional activation of IL
      17 and its downstream signaling in Jurkat T-lymphocytes upon high glucose
      treatment. Candidate genes like Interleukin (IL)-17A, IL-17E IL-17F and IL-6 were
      up-regulated in both Jurkat T-lymphocytes and PBLCs from normal and diabetes
      subjects. This high glucose induced cytokine expression was due to promoter
      activation. Pharmacology inhibitor studies showed the involvement of NF-kappaB,
      protein kinase-C, p38 Mitogen activated protein kinase; Janus activated kinase
      signal transducer and activator of transcription and extracellular regulated
      kinase signaling pathways. Further, high glucose treatment increased the adhesion
      of lymphocytes to human umbilical vein endothelial cells. These results show that
      IL-17 cytokines are induced by high glucose via key signaling pathways leading to
      lymphocyte activation and relevant to the pathogenesis of diabetic complications
      like atherosclerosis. 

PMID- 24308967
TI  - The role of plasma membrane STIM1 and Ca(2+)entry in platelet aggregation. STIM1
      binds to novel proteins in human platelets.
AB  - Ca(2+) elevation is essential to platelet activation. STIM1 senses Ca(2+) in the
      endoplasmic reticulum and activates Orai channels allowing store-operated Ca(2+)
      entry (SOCE). STIM1 has also been reported to be present in the plasma membrane
      (PM) with its N-terminal region exposed to the outside medium but its role is not
      fully understood. We have examined the effects of the antibody GOK/STIM1, which
      recognises the N-terminal region of STIM1, on SOCE, agonist-stimulated Ca(2+)
      entry, surface exposure, in vitro thrombus formation and aggregation in human
      platelets. We also determined novel binding partners of STIM1 using proteomics.
      The dialysed GOK/STIM1 antibody failed to reduced thapsigargin- and agonist
      mediated Ca(2+) entry in Fura2-labelled cells. Using flow cytometry we detect a
      portion of STIM1 to be surface-exposed. The dialysed GOK/STIM1 antibody reduced
      thrombus formation by whole blood on collagen-coated capillaries under flow and
      platelet aggregation induced by collagen. In immunoprecipitation experiments
      followed by proteomic analysis, STIM1 was found to extract a number of proteins
      including myosin, DOCK10, thrombospondin-1 and actin. These studies suggest that
      PM STIM1 may facilitate platelet activation by collagen through novel
      interactions at the plasma membrane while the essential Ca(2+)-sensing role of
      STIM1 is served by the protein in the ER. 

PMID- 24308970
TI  - The guanine nucleotide exchange factor Tiam1: a Janus-faced molecule in cellular
      signaling.
AB  - The Rho family of GTPases consists of several small proteins that have been
      described as molecular switches, playing important roles in a wide variety of
      fundamental cellular processes and in human diseases such as cancer. These
      proteins, active in the GTP conformation and inactive in the GDP form, are in
      turn regulated by guanine nucleotide exchange factors (GEFs), guanine nucleotide
      activating proteins (GAPs) and guanine dissociation inhibitors (GDIs). Two
      decades ago, Tiam1 (T-lymphoma invasion and metastasis) was identified as a GEF
      specific for Rac1 activation, but also for Cdc42 and in a lesser extent RhoA.
      Acting principally upstream of Rac1, Tiam1 is mainly involved in the regulation
      of Rac1 mediated signaling pathways including cytoskeletal activities, cell
      polarity, endocytosis and membrane trafficking, cell migration, adhesion and
      invasion, cell growth and survival, metastasis and carcinogenesis. However, given
      the large number of protein interaction domains found in its structure, it is
      possible that Tiam1 affects cellular processes in another way than through its
      GEF activity by interactions with other signaling proteins. Due to its functional
      diversity, Tiam1 is involved in multiple steps of tumorigenesis. As its name
      suggests, Tiam1 has been shown to increase T-cell lymphoma invasion and
      metastasis. It also promotes migration of fibroblasts, neuronal and cancer cells.
      On the contrary, Tiam1-induced cell adhesion has also been described, as opposed
      to cell migration. Moreover, studies indicate that Tiam1 is involved in both anti
      apoptotic and pro-apoptotic mechanisms. While increasing evidence has
      demonstrated Tiam1's contribution to tumorigenesis and metastasis, others suggest
      that Tiam1 could have anti-cancer properties. In the present review, we discuss
      the current knowledge about the controversial roles of Tiam1 in cellular
      signaling. In particular, we will focus on Tiam1's regulation, its biological
      functions and implication in cancer. 

PMID- 24308968
TI  - The role of cell signalling in the crosstalk between autophagy and apoptosis.
AB  - Not surprisingly, the death of a cell is a complex and well controlled process.
      For several decades, apoptosis, the first genetically programmed death process to
      be identified has taken centre stage as the principal mechanism of programmed
      cell death (type I cell death) in mammalian tissues. Apoptosis has been
      extensively studied and its contribution to the pathogenesis of disease well
      documented. However, apoptosis does not function alone in determining the fate of
      a cell. More recently, autophagy, a process in which de novo formed membrane
      enclosed vesicles engulf and consume cellular components, has been shown to
      engage in complex interplay with apoptosis. As a result, cell death has been
      subdivided into the categories apoptosis (Type I), autophagic cell death (Type
      II), and necrosis (Type III). The boundary between Type I and II cell death is
      not completely clear and as we will discuss in this review and perhaps a discrete
      difference does not exist, due to intrinsic factors among different cell types
      and crosstalk among organelles within each cell type. Apoptosis may begin with
      autophagy and autophagy can often end with apoptosis, inhibition or a blockade of
      caspase activity may lead a cell to default into Type II cell death from Type I. 

PMID- 24308969
TI  - Bilirubin mediated oxidative stress involves antioxidant response activation via
      Nrf2 pathway.
AB  - Unconjugated bilirubin (UCB) is responsible for neonatal jaundice and high level
      of free bilirubin (Bf) can lead to kernicterus. Previous studies suggest that
      oxidative stress is a critical component of UCB-induced neurotoxicity. The Nrf2
      pathway is a powerful sensor for cellular redox state and is activated directly
      by oxidative stress and/or indirectly by stress response protein kinases.
      Activated Nrf2 translocates to nucleus, binds to Antioxidant Response Element
      (ARE), and enhances the up-regulation of cytoprotective genes that mediate cell
      survival. The aim of the present study was to investigate the role of Nrf2
      pathway in cell response to bilirubin mediated oxidative stress in the
      neuroblastoma SH-SY5Y cell line. Cells exposed to a toxic concentration of UCB
      (140 nM Bf) showed an increased intracellular ROS levels and enhanced nuclear
      accumulation of Nrf2 protein. UCB stimulated transcriptional induction of ARE-GFP
      reporter gene and induced mRNA expression of multiple antioxidant response genes
      as: xCT, Gly1, gammaGCL-m, gammaGCL-c, HO-1, NQO1, FTH, ME1, and ATF3. Nrf2 siRNA
      decreased UCB induced mRNA expression of HO1 (75%), NQO1 (54%), and FTH (40%).
      The Nrf2-related HO-1 induction was reduced to 60% in cells pre-treated with
      antioxidant (NAC) or specific signaling pathway inhibitors for PKC, P38alpha and
      MEK1/2 (80, 40 and 25%, respectively). In conclusion, we demonstrated that SH
      SY5Y cells undergo an adaptive response against UCB-mediated oxidative stress by
      activation of multiple antioxidant response, in part through Nrf2 pathway.

PMID- 24308971
TI  - Dopamine D3 receptor inhibits the ubiquitin-specific peptidase 48 to promote NHE3
      degradation.
AB  - The dopamine D3 receptor (D3R) is crucial in the regulation of blood pressure and
      sodium balance, in that Drd3 gene ablation in mice results in hypertension and
      failure to excrete a dietary salt load. The mechanism responsible for the renal
      sodium retention in these mice is largely unknown. We now offer and describe a
      novel mechanism by which D3R decreases sodium transport in the long term by
      inhibiting the deubiquitinylating activity of ubiquitin-specific peptidase 48
      (USP48), thereby promoting Na(+)-H(+) exchanger (NHE)-3 degradation. We found
      that stimulation with the D3R-specific agonist PD128907 (1 MUM, 30 min) promoted
      the interaction and colocalization among D3R, NHE3, and USP48; inhibited USP48
      activity (-35+/-6%, vs. vehicle), resulting in increased ubiquitinylated NHE3
      (+140+/-10%); and decreased NHE3 expression (-50+/-9%) in human renal proximal
      tubule cells (hRPTCs). USP48 silencing decreased NHE3's half-life (USP48 siRNA
      t1/2=6.1 h vs. vehicle t1/2=12.9 h), whereas overexpression of USP48 increased
      NHE3 half-life (t1/2=21.8 h), indicating that USP48 protects NHE3 from
      degradation via deubiquitinylation. USP48 accounted for ~30% of the total
      deubiquitinylating activity in these cells. Extending our studies in vivo, we
      found that pharmacologic blockade of D3R via the D3R-specific antagonist GR103691
      (1 MUg/kg/min, 4 d) in C57Bl/6J mice increased renal NHE3 expression (+310+/-15%,
      vs. vehicle), whereas an innovative kidney-restricted Usp48 silencing via siRNA
      (3 MUg/d, 7 d) increased ubiquitinylated NHE3 (+250+/-30%, vs. controls),
      decreased total NHE3 (-23+/-2%), and lowered blood pressure (-24+/-2 mm Hg),
      compared with that in control mice that received either the vehicle or
      nonsilencing siRNA. Our data demonstrate a crucial role for the dynamic
      interaction between D3R and USP48 in the regulation of NHE3 expression and
      function.

PMID- 24308972
TI  - Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate
      cancer progression and development.
AB  - The bone morphogenetic protein (BMP) signaling pathways have important roles in
      embryonic development and cellular homeostasis, with aberrant BMP signaling
      resulting in a broad spectrum of human disease. We report that BMPs unexpectedly
      signal through the canonical transforming growth factor beta (TGF-beta)
      responsive Smad2 and Smad3. BMP-induced Smad2/3 signaling occurs preferentially
      in embryonic cells and transformed cells. BMPs signal to Smad2/3 by stimulating
      complex formation between the BMP-binding TGF-beta superfamily receptors, activin
      receptor-like kinase (ALK)3/6, and the Smad2/3 phosphorylating receptors ALK5/7.
      BMP signaling through Smad2 mediates, in part, dorsoventral axis patterning in
      zebrafish embryos, whereas BMP signaling through Smad3 facilitates cancer cell
      invasion. Consistent with increased BMP-mediated Smad2/3 signaling during cancer
      progression, Smad1/5 and Smad 2/3 signaling converge in human cancer specimens.
      Thus, the signaling mechanisms used by BMPs and TGF-beta superfamily receptors
      are broader than previously appreciated.

PMID- 24308973
TI  - Roles of receptor activity-modifying protein 1 in angiogenesis and
      lymphangiogenesis during skin wound healing in mice.
AB  - Receptor activity-modifying protein 1 (RAMP1) forms a complex with calcitonin
      receptor-like receptor (CLR) to produce the receptor for calcitonin gene-related
      peptide (CGRP). CGRP, a 37-aa neuropeptide, is widely distributed in neuronal
      tissues and exerts its biological effects via CLR/RAMP1; however, the
      pathophysiological roles of CLR/RAMP1 remain to be clarified. To study the
      functions of CLR/RAMP1, we generated RAMP1-knockout (RAMP1(-/-)) mice. Compared
      with those of wild-type (WT) mice, wound healing and wound-induced angiogenesis
      were significantly suppressed in RAMP1(-/-) mice, with reduced expression of
      vascular endothelial growth factor (VEGF)-A. Formation of the lymphatic vessels
      that drain interstitial fluids was also suppressed in RAMP1(-/-) mice, with
      reduced expression of VEGF-C and VEGFR-3 in wound granulation tissues. RAMP1 was
      expressed in endothelial cells (ECs) in the preexisting skin blood vessels, but
      was not observed in ECs in newly formed blood or lymphatic vessels. Macrophages
      in the wound granulation tissues expressed RAMP1 and produced substantial amounts
      of VEGF-C in response to CGRP in vitro. RAMP1(-/-) bone marrow chimeric mice
      showed delayed wound healing with reduced angiogenesis/lymphangiogenesis in wound
      granulation tissues. These findings suggest that RAMP1 plays a crucial role in
      wound healing and wound-induced angiogenesis and lymphangiogenesis and that it is
      a promising target for controlling angiogenesis and lymphangiogenesis.

PMID- 24308974
TI  - Rapid evolution of binding specificities and expression patterns of inhibitory
      CD33-related Siglecs in primates.
AB  - Siglecs are sialic acid-binding Ig-like lectins that recognize sialoglycans via
      amino-terminal V-set domains. CD33-related Siglecs (CD33rSiglecs) on innate
      immune cells recognize endogenous sialoglycans as "self-associated molecular
      patterns" (SAMPs), dampening immune responses via cytosolic immunoreceptor
      tyrosine-based inhibition motifs that recruit tyrosine phosphatases. However,
      sialic acid-expressing pathogens subvert this mechanism through molecular
      mimicry. Meanwhile, endogenous host SAMPs must continually evolve to evade other
      pathogens that exploit sialic acids as invasion targets. We hypothesized that
      these opposing selection forces have accelerated CD33rSiglec evolution. We
      address this by comparative analysis of major CD33rSiglec (Siglec-3, Siglec-5,
      and Siglec-9) orthologs in humans, chimpanzees, and baboons. Recombinant soluble
      molecules displaying ligand-binding domains show marked quantitative and
      qualitative interspecies differences in interactions with strains of the
      sialylated pathogen, group B Streptococcus, and with sialoglycans presented as
      gangliosides or in the form of sialoglycan microarrays, including variations such
      as N-glycolyl and O-acetyl groups. Primate Siglecs also show quantitative and
      qualitative intra- and interspecies variations in expression patterns on
      leukocytes, both in circulation and in tissues. Taken together our data explain
      why the CD33rSiglec-encoding gene cluster is undergoing rapid evolution via
      multiple mechanisms, driven by the need to maintain self-recognition by innate
      immune cells, while escaping 2 distinct mechanisms of pathogen subversion.

PMID- 24308976
TI  - Dosage-dependent regulation of cell proliferation and adhesion through dual beta2
      adrenergic receptor/cAMP signals.
AB  - The role of beta-adrenergic receptors (beta-ARs) remains controversial in normal
      and tumor breast. Herein we explore the cAMP signaling involved in beta-AR
      dependent control of proliferation and adhesion of nontumor human breast cell
      line MCF-10A. Low concentrations of a beta-agonist, isoproterenol (ISO), promote
      cell adhesion (87.5% cells remaining adherent to the plastic dishes following
      specific detachment vs. 35.0% in control, P<0.001), while increasing
      concentrations further engages an additional 36% inhibition of Erk1/2
      phosphorylation (p-Erk1/2)-dependent cell proliferation (P<0.01). Isoproterenol
      dose response on cell adhesion was fitted to a 2-site curve (EC50(1): 16.5+/-11.5
      fM, EC50(2): 4.08+/-3.09 nM), while ISO significantly inhibited p-Erk1/2
      according to a 1-site model (EC50: 0.25+/-0.13 nM). Using beta-AR-selective
      agonist/antagonists and cAMP analogs/inhibitors, we identified a dosage-dependent
      signaling in which low ISO concentrations target a beta2-AR population localized
      in raft microdomains and stimulate a Gs/cAMP/Epac/adhesion-signaling module,
      while higher concentrations engage a concomitant activation of another beta2-AR
      population outside rafts and inhibit the proliferation by a Gs/cAMP/PKA-dependent
      signaling module. Our data provide a new molecular basis for the dose-dependent
      switch of beta-AR signaling. This study also sheds light on a new cAMP pathway
      core mechanism with a single receptor triggering dual cAMP signaling controlled
      by PKA or Epac but with different cellular outputs.

PMID- 24308977
TI  - Using surgical drapes to facilitate pedicle deepithelialization in reduction
      mammoplasty.

PMID- 24308975
TI  - Follicle-stimulating hormone synthesis and fertility are intact in mice lacking
      SMAD3 DNA binding activity and SMAD2 in gonadotrope cells.
AB  - The activin/inhibin system regulates follicle-stimulating hormone (FSH) synthesis
      and release by pituitary gonadotrope cells in mammals. In vitro cell line data
      suggest that activins stimulate FSH beta-subunit (Fshb) transcription via
      complexes containing the receptor-regulated SMAD proteins SMAD2 and SMAD3. Here,
      we used a Cre-loxP approach to determine the necessity for SMAD2 and/or SMAD3 in
      FSH synthesis in vivo. Surprisingly, mice with conditional mutations in both
      Smad2 and Smad3 specifically in gonadotrope cells are fertile and produce FSH at
      quantitatively normal levels. Notably, however, we discovered that the recombined
      Smad3 allele produces a transcript that encodes the entirety of the SMAD3 C
      terminal Mad homology 2 (MH2) domain. This protein behaves similarly to full
      length SMAD3 in Fshb transcriptional assays. As the truncated protein lacks the N
      terminal Mad homology 1 (MH1) domain, these results show that SMAD3 DNA-binding
      activity as well as SMAD2 are dispensable for normal FSH synthesis in vivo.
      Furthermore, the observation that deletion of proximal exons does not remove all
      SMAD3 function may facilitate interpretation of divergent phenotypes previously
      described in different Smad3 knockout mouse lines.

PMID- 24308978
TI  - Predictive value for the rural Chinese population of the Framingham hypertension
      risk model: results from Liaoning Province.
AB  - BACKGROUND: A prediction model from the US Framingham Heart Study (FHS)
      population has been established to estimate an individual's risk of developing
      hypertension. However, this model has not been widely tested in other cohorts. In
      this study, we examined the predictive capability of the FHS prediction model in
      a rural Chinese population. METHODS: A total of 24,434 rural Chinese adults aged
      >=35 years, without prevalent hypertension, diabetes mellitus, stroke, and
      coronary heart disease at baseline, were followed for the incidence of
      hypertension. Standard clinical examinations of blood pressure, weight and
      height, smoking status, and parental history of hypertension were observed
      biennially. RESULTS: The mean age was 47.9 (SD = 10.2) years, and 49.5% of
      subjects were women. During a median 4.8 years of follow-up, we recorded a total
      of 8,675 incident hypertension cases. The cumulative 2-year and 4-year
      hypertension incidence rates were 7.7% and 25.6%, respectively. The C statistics
      for the 2-year and 4-year incidences of hypertension were 0.537 (95% confidence
      interval (CI) = 0.524-0.550) and 0.610 (95% CI = 0.602-0.618) for the FHS model,
      respectively. The Hosmer-Lemeshow chi(2) test results for 2-year and 4-year
      incidence of hypertension were 2,287.7 (P < 0.0001) and 8,227.1 (P < 0.0001),
      respectively. Sensitivity analysis indicates that the FHS prediction model still
      has a poor performance, although the predictive ability was better than for the
      overall population. CONCLUSIONS: The FHS hypertension prediction model is not a
      valid tool with which to estimate the risk of incidence of hypertension among the
      rural Chinese population. A new hypertension risk equation for the rural Chinese
      population is needed.

PMID- 24308979
TI  - Surveillance of human immunodeficiency virus suggests that younger men who have
      sex with men are at higher risk of infection, European Union, 2003 to 2012.
AB  - In 2012, newly reported human immunodeficiency virus diagnoses in the European
      Union /European Economic Area remained stable at around 30,000 cases. Since 2003,
      cases in men who have sex with men (MSM) aged 20 to 29 years-old doubled, while
      the proportion of late presenters in this group remained stable. Persistent
      declines occurred among older MSM age groups, particularly that between 30 and 39
      years-old. Interventions targeting younger MSM are needed to prevent a resurgence
      of the epidemic in Europe.

PMID- 24308980
TI  - Human immunodeficiency virus among people who inject drugs: is risk increasing in
      Europe?
AB  - In most European Union (EU)/European Economic Area (EEA) countries, between 2010
      and 2012, reports of new human immunodeficiency virus (HIV) diagnoses among
      people who inject drugs have been stable or declining. HIV outbreaks in Greece
      and Romania, first reported in 2011, continue and economic conditions hinder
      provision of effective response coverage. When measured against some established
      thresholds, prevention coverage remains inadequate in at least one-third of
      EU/EEA countries. Urgent consideration to scale up prevention efforts is merited.

PMID- 24308981
TI  - Increase of new HIV diagnoses among men who have sex with men in Poland, 2000 to
      2011.
AB  - Re-emergence of the human immunodeficiency virus (HIV) epidemic among men who
      have sex with men (MSM) has been observed in countries of western Europe, North
      America and Australia since the mid-1990s. We aimed to describe the trends in
      notification rate of HIV infection among MSM in Poland in order to provide
      evidence for further public health action. We performed a descriptive analysis of
      2000-11 surveillance data, accounting for missing information on transmission
      category through multiple imputations. There were 9,286 new HIV diagnoses in
      Poland in 2000-11, ranging from 546 to 1,095 per year. A total of 6,896 cases
      were male, 1,943 female. For 5,615 (60.5%) new diagnoses, the transmission
      category was not reported; among the rest, MSM constituted 24.1% (n=885/3,671).
      The rate of new HIV diagnoses among MSM per million men increased from 2.5 in
      2000 to 33.8 in 2011; in the Mazowieckie region, which includes Warsaw, it rose
      from 2.2 to 88.8, when adjusting for missing data on transmission category. Our
      results suggest the need for enhanced, comprehensive prevention among MSM,
      especially in regions where the increasing rate of new HIV diagnoses suggests
      ongoing transmission.

PMID- 24308982
TI  - Antiretroviral therapy for prevention of HIV transmission: implications for
      Europe.
AB  - The aim of this review is to summarise the evidence on the population-level
      effect of antiretroviral therapy (ART) in preventing HIV infections, and to
      discuss potential implications in the European context of recommending starting
      ART when the CD4 count is above 350 cells/mm3. The ability of ART to reduce the
      risk of HIV transmission has been reported in observational studies and in a
      randomised controlled trial (HPTN 052), in which ART initiation reduced HIV
      transmission by 96% within serodiscordant couples. As yet, there is no direct
      evidence for such an effect among men having sex with men or people who inject
      drugs. HPTN 052 led international organisations to develop recommendations with a
      higher CD4 threshold for ART initiation. However, there remains a lack of strong
      evidence of clinical benefit for HIV-positive individuals starting ART with CD4
      count above 350 cells/mm3. The main goal of ART provision should be to increase
      ART coverage for all those in need, based on the current guidelines, and the
      offer of ART to those who wish to reduce infectivity; increased HIV testing is
      therefore a key requirement. Other proven prevention means such as condom use and
      harm reduction for people who inject drugs remain critical.

PMID- 24308983
TI  - Special Eurobarometer reveals television as main source of information for
      developments in science and technology.

PMID- 24308986
TI  - Water stress reveals differential antioxidant responses of tolerant and non
      tolerant sugarcane genotypes.
AB  - The biochemical responses of the enzymatic antioxidant system of a drought
      tolerant cultivar (IACSP 94-2094) and a commercial cultivar in Brazil (IACSP 95
      5000) grown under two levels of soil water restriction (70% and 30% Soil
      Available Water Content) were investigated. IACSP 94-2094 exhibited one
      additional active superoxide dismutase (Cu/Zn-SOD VI) isoenzyme in comparison to
      IACSP 95-5000, possibly contributing to the heightened response of IACSP 94-2094
      to the induced stress. The total glutathione reductase (GR) activity increased
      substantially in IACSP 94-2094 under conditions of severe water stress; however,
      the appearance of a new GR isoenzyme and the disappearance of another isoenzyme
      were found not to be related to the stress response because the cultivars from
      both treatment groups (control and water restrictions) exhibited identical
      changes. Catalase (CAT) activity seems to have a more direct role in H2O2
      detoxification under water stress condition and the shift in isoenzymes in the
      tolerant cultivar might have contributed to this response, which may be dependent
      upon the location where the excessive H2O2 is being produced under stress. The
      improved performance of IACSP 94-2094 under drought stress was associated with a
      more efficient antioxidant system response, particularly under conditions of mild
      stress. 

PMID- 24308987
TI  - AtObgC-AtRSH1 interaction may play a vital role in stress response signal
      transduction in Arabidopsis.
AB  - The interaction of Obg (Spo0B-associated GTP-binding protein) GTPase and SpoT,
      which is a bifunctional ppGpp (guanosine 3',5'-bispyrophosphate)
      hydrolase/synthetase, is vital for the modulation of intracellular ppGpp levels
      during bacterial responses to environmental cues. It has been recently reported
      that the ppGpp level is also inducible by various stresses in the chloroplasts of
      plant cells. However, the function of the Obg-SpoT interaction in plants remains
      elusive. The results from the present and previous studies suggest that AtRSH1 is
      a putative bacterial SpoT homolog in Arabidopsis and that its transcription
      levels are responsive to wounding and salt stresses. In this study, we used a
      yeast two-hybrid analysis to map the regions required for the AtObgC-AtRSH1
      interaction. Moreover, protein-protein docking simulations revealed reasonable
      geometric and electrostatic complementarity in the binding surfaces of the two
      proteins. The data support our experimental results, which suggest that the
      conserved domains in AtObgC and the N terminus of AtRSH1 containing the TGS
      domain contribute to their interaction. In addition, quantitative real-time PCR
      (qRT-PCR) analyses showed that the expression of AtObgC and AtRSH1 exhibit a
      similar inhibition pattern under wounding and salt-stress conditions, but the
      inhibition pattern was not greatly influenced by the presence or absence of
      light. Based on in vivo analyses, we further confirmed that the AtRSH1 and AtObgC
      proteins similarly localize in chloroplasts. Based on these results, we propose
      that the AtObgC-AtRSH1 interaction plays a vital role in ppGpp-mediated stress
      responses in chloroplasts.

PMID- 24308988
TI  - Multiple heat priming enhances thermo-tolerance to a later high temperature
      stress via improving subcellular antioxidant activities in wheat seedlings.
AB  - Seedlings of winter wheat (Triticum aestivum L.) were firstly twice heat-primed
      at 32/24  degrees C, and subsequently subjected to a more severe high temperature
      stress at 35/27  degrees C. The later high temperature stress significantly
      decreased plant biomass and leaf total soluble sugars concentration. However,
      plants experienced priming (PH) up-regulated the Rubisco activase B encoding gene
      RcaB, which was in accordance with the higher photosynthesis rate in relation to
      the non-primed plants (NH) under the later high temperature stress. In relation
      to NH, the major chlorophyll a/b-binding protein gene Cab was down-regulated in
      PH plants, implying a reduction of the light absorption to protect the
      photosystem II from excitation energy under high temperature stress. At the same
      time, under the later high temperature stress PH plants showed significantly
      higher actual photochemical efficiency, indicating an improvement of light use
      efficiency due to the priming pre-treatment. Under the later high temperature
      stress, PH could be maintained a better redox homeostasis than NH, as exemplified
      by the higher activities of superoxide dismutase (SOD) in chloroplasts and
      glutathione reductase (GR), and of peroxidase (POD) in mitochondria, which
      contributed to the lower superoxide radical production rate and malondialdehyde
      concentration in both chloroplasts and mitochondria. The improved antioxidant
      capacity in chloroplasts and mitochondria was related to the up-regulated
      expressions of Cu/Zn-SOD, Mn-SOD and GR in PH. Collectively, heat priming
      effectively improved thermo-tolerance of wheat seedlings subjected to a later
      high temperature stress, which could be largely ascribed to the enhanced anti
      oxidation at the subcellular level.

PMID- 24308989
TI  - Molecular characterization and expression analysis of the small GTPase ROP
      members expressed in laticifers of the rubber tree (Hevea brasiliensis).
AB  - ROP (Rho of plants) proteins are plant-specific Rho-type small GTPases which play
      important roles in cellular processes and stress responses. This study explores
      the characteristics and possible functions of ROPs that are expressed primarily
      in laticifers of the rubber tree (Hevea brasiliensis). The work serves as a
      preliminary step to determining their involvement in latex flow and regeneration,
      laticifers formation and tapping panel dryness (TPD, a physiological disorder in
      rubber trees that result in the stoppage of latex flow). In this connection, we
      (i) identified five HbROPs (HbROP1-HbROP5) by searching latex transcripts
      database and the genome databases, (ii) characterized molecular and phylogenic
      aspects of the HbROPs and examined the cis-regulatory elements in their promoter
      regions; (iii) analyzed by Real-time Quantitative PCR (QPCR) the tissue
      specificity of the HbROPs and their expression patterns in response to tapping,
      bark wounding and growth regulator treatments. All five HbROP genes were strongly
      expressed in the latex, with HbROP1, 3, 4 and 5 showing the highest expression
      among the six Hevea tissues examined, viz. latex, bud, mature leaf, bark, male
      flower and seed. When tapping was initiated on previously untapped trees, HbROP3
      transcription was substantially down-regulated whereas HbROP5 expression was
      markedly up-regulated. Transcripts of HbROP3 rose gradually with the development
      of TPD. Except for the cytokinin 6-benzyl aminopurine that induced a rise in
      HbROP5 transcripts by more than 2-fold, the other growth regulators tested had
      little effect on HbROPs expression. The roles of HbROPs in rubber tree are
      discussed in relation to the diverse functions of ROP homologs reported in other
      plant species. 

PMID- 24308990
TI  - Brain lactate in hepatic encephalopathy: friend or foe?

PMID- 24308991
TI  - Active at night, sleepy all day--sleep disturbances in patients with hepatitis C
      virus infection.
AB  - BACKGROUND & AIMS: More than 50% of patients with chronic hepatitis C with only
      mild liver disease complain about chronic fatigue, daytime sleepiness and poor
      sleep quality. The aim of the present study was to characterize and objectify the
      sleep disturbances in hepatitis C virus-infected patients. METHODS: Twenty-five
      women who had been infected with hepatitis C virus contaminated anti-D
      immunoglobulin in 1978/79 and 22 age-matched female healthy controls underwent
      actigraphy over a period of 5 days to measure motor activity and thereby sleep
      wake-rhythm and in addition completed questionnaires for depression, health
      related quality of life, fatigue and sleep, and a sleep diary. Liver cirrhosis, a
      history of neurological or psychiatric disease, history of intravenous drug
      abuse, shift work, or current medication with effect upon the central nervous
      system were exclusion criteria. RESULTS: The patients achieved higher scores for
      depression, fatigue and sleep disturbances and lower quality of life scores than
      the healthy controls. Actigraphy showed higher nocturnal activity and worse sleep
      efficiency in the patients, while the 24-h activity level did not differ between
      groups. Fatigue and quality of life scores correlated with bad sleep quality and
      daytime sleepiness. CONCLUSIONS: Our data indicate that chronic fatigue is
      associated with bad sleep quality and increased nocturnal activity in HCV
      infected patients suggesting an alteration of sleep architecture behind fatigue
      in HCV-associated encephalopathy.

PMID- 24308992
TI  - Notch signaling and new therapeutic options in liver disease.
AB  - Notch signaling is a crucial determinant of cell fate decision during development
      and disease in several organs. Notch effects are strictly dependent on the
      cellular context in which it is activated. In the liver, Notch signaling is
      involved in biliary tree development and tubulogenesis. Recent advances have shed
      light on Notch as a critical player in liver regeneration and repair, as well as
      in liver metabolism and inflammation and cancer. Notch signaling is finely
      regulated at several levels. The complexity of the pathway provides several
      possible targets for development of therapeutic agents able to inhibit Notch.
      Recent reports have shown that persistent activation of Notch signaling is
      associated with liver malignancies, particularly hepatocellular with stem cell
      features and cholangiocarcinoma. These novel findings suggest that interfering
      with the aberrant activation of the Notch pathway may have therapeutic relevance.
      However, further studies are needed to clarify the mechanisms regulating
      physiologic and pathologic Notch activation in the adult liver, to better
      understand the mechanistic role(s) of Notch in liver diseases and to develop safe
      and specific therapeutic agents. 

PMID- 24308994
TI  - Dependence of eelgrass (Zostera marina) light requirements on sediment organic
      matter in Massachusetts coastal bays: implications for remediation and
      restoration.
AB  - Using a calibrated bio-optical model we determined that the optical water quality
      conditions in several nitrogen-impaired embayments and in one unimpaired system
      were within the range of values known to support eelgrass growth. We also used
      the model to identify a range of light requirements for eelgrass (Zostera
      marina). Higher eelgrass light requirements, expressed as a percentage of surface
      incident irradiance, corresponded with higher sediment organic matter content.
      These results corroborated findings by previous studies which indicate a
      generalized relationship: seagrasses growing in turbid conditions with poorer
      water and sediment quality have higher light requirements than those growing in
      less degraded conditions. The mechanistic reason for the variation in light
      requirements is still not completely explained and cannot be attributed to a
      single independent variable. Varying light requirement have important
      implications for eelgrass protection and should be considered when setting
      restoration targets for eelgrass in water quality and nitrogen remediation
      programs. 

PMID- 24308995
TI  - Trace metal pyritization variability in response to mangrove soil aerobic and
      anaerobic oxidation processes.
AB  - The degree of iron pyritization (DOP) and degree of trace metal pyritization
      (DTMP) were evaluated in mangrove soil profiles from an estuarine area located in
      Rio de Janeiro (SE Brazil). The soil pH was negatively correlated with redox
      potential (Eh) and positively correlated with DOP and DTMP of some elements (Mn,
      Cu and Pb), suggesting that pyrite oxidation generated acidity and can affect the
      importance of pyrite as a trace metal-binding phase, mainly in response to
      spatial variability in tidal flooding. Besides these aerobic oxidation effects,
      results from a sequential extraction analyses of reactive phases evidenced that
      Mn oxidized phase consumption in reaction with pyrite can be also important to
      determine the pyritization of trace elements. Cumulative effects of these aerobic
      and anaerobic oxidation processes were evidenced as factors affecting the
      capacity of mangrove soils to act as a sink for trace metals through pyritization
      processes. 

PMID- 24308993
TI  - Targeting the mTOR pathway in hepatocellular carcinoma: current state and future
      trends.
AB  - Mechanistic target of rapamycin (mTOR) regulates cell growth, metabolism and
      aging in response to nutrients, cellular energy stage and growth factors. mTOR is
      frequently up-regulated in cancer including hepatocellular carcinoma (HCC) and is
      associated with bad prognosis, poorly differentiated tumors, and earlier
      recurrence. Blocking mTOR with rapamycin and first generation mTOR inhibitors,
      called rapalogs, has shown promising reduction of HCC tumor growth in preclinical
      models. Currently, rapamycin/rapalogs are used in several clinical trials for the
      treatment of advanced HCC, and as adjuvant therapy in HCC patients after liver
      transplantation and TACE. A second generation of mTOR pathway inhibitors has been
      developed recently and is being tested in various clinical trials of solid
      cancers, and has been used in preclinical HCC models. The results of series of
      clinical trials using mTOR inhibitors in HCC treatment will emerge in the near
      future. 

PMID- 24308996
TI  - Male reproductive biology of Aedes mosquitoes.
AB  - Among Aedes mosquitoes are species responsible for transmission of serious
      pathogens to humans. To cope with the current threats to long-term effectiveness
      of the traditional vector control methods, non-conventional control strategies
      are being developed. These include autocidal control such as the release of
      sterile males (sterile insect technique) and the release of Wolbachia-infected
      males to induce sexual sterility (incompatible insect technique) and pathogen
      refractory strain replacement variations using Wolbachia. Sterile male types of
      techniques particularly depend on released males' ability to successfully mate
      with wild females. For that reason, a good understanding of male mating biology,
      including a thorough understanding of the reproductive system and mating
      capacity, increases the likelihood of success of such genetic vector control
      programmes. Here we review the literature concerning the reproduction of Aedes
      mosquitoes with an emphasis on the male biology. We consider sexual maturation,
      mate finding, insemination, male reproductive capacity, and the occurrence of
      multiple matings. We also discuss which parameters are of greatest importance for
      the successful implementation of autocidal control methods and propose questions
      for future research. 

PMID- 24308997
TI  - Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors.
AB  - Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra
      substituted indole derivatives as novel AKT inhibitors by optimization of a weak
      hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative
      compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1,
      with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of
      10nM. In addition, compounds 6a and 6o also potently inhibited the
      phosphorylation of the downstream GSK3 protein and displayed slightly better anti
      proliferative activities in a prostate cancer cell line. 

PMID- 24308998
TI  - 1,2,4-Triazole/oxime hybrids as new strategy for nitric oxide donors: Synthesis,
      anti-inflammatory, ulceroginicity and antiproliferative activities.
AB  - A series of novel nitric oxide (NO) donating triazole/oxime hybrids was prepared
      and evaluated for their anti-inflammatory activity and antiproliferative
      activity. Most of the tested compounds showed significant anti-inflammatory
      activity using carrageenan-induced rat paw edema method compared to indomethacin.
      Calculation of the ulcer indices and histopathological investigation indicated
      that the prepared NO-donating oximes exhibited less ulcerogenicity compared to
      their ketone intermediates and indomethacin. The NO-donating oximes 7i and 7k
      achieved remarkable cell growth inhibition activity against most of the tested
      cell lines. Compound 7k was found to be with high selectivity against CNS
      subpanel with selectivity ratio of 11.99 at GI50 level.

PMID- 24308999
TI  - Synthesis and tumor cell growth inhibitory activity of biotinylated annonaceous
      acetogenins.
AB  - Nineteen biotinylated squamocin/bullatacin derivatives have been synthesized for
      targeted delivery to biotin receptor overexpressed tumor cells. Most biotinylated
      squamocin and bullatacin derivatives show similar in vitro cytotoxicity against
      the biotin receptor non-overexpressed L1210 cells as squamocin and bullatacin,
      respectively, while against biotin receptor overexpressed 4T1 and P815 tumor
      cells, several derivatives show significantly higher potency and better
      selectivity. Among all the synthesized compounds, 15,28-di-O-(6
      biotinylamidohexanoyl)squamocin (16) is the most potent, which is 10 and 26 times
      more active than squamocin against 4T1 and P815 cells, respectively. Compound 16
      also appears to be six and fifteen times more selective than squamocin towards
      4T1 and P815 cells, respectively, against L1210 cells. The structure activity
      relationship analysis has revealed that the preferred site for biotinylation is
      different for squamocin and bullatacin, and it also depends on whether a linking
      spacer is present.

PMID- 24309000
TI  - Synthesis, characterization and anticancer screening of some novel piperonyl
      tetrazole derivatives.
AB  - A series of new 1,2-substituted tetrazole derivatives were synthesized and
      evaluated on MCF-7 (ER positive), MDA-MB-231 and ZR-75 (ER negative) breast
      cancer cell lines. Out of the fourteen compounds, three compounds 10, 12 and 14
      showed higher inhibitory effects on MCF-7 cells. Whereas, compound 8 exhibited
      higher inhibition in MDA-MB-231 and ZR-75 cells at 10(-5) M concentration. Total
      RNA was extracted and effect of compounds on different marker genes was studied.
      The gene expression of CD44, BRAC and BAX were significantly affected. The
      compounds were screened against the HepG2 cell line, to know if they are
      selectively targeting specific cancers and only 1-10 percent inhibition was found
      at 10(-5) M concentration.

PMID- 24309001
TI  - Expression of so-called adhesion proteins and DNA cytometric analysis in
      malignant parotid tumours as predictors of clinical outcome.
AB  - Tumours of the salivary glands are rare, and account for only 0.5-1% of all
      tumours. We have analysed the cytoarchitectural structure of such tumours by
      studying 3 binding proteins that act on different parts of the glandular
      epithelial architecture: e-cadherin, laminin, and CD44. We analysed the DNA using
      image cytometry to evaluate ploidy, S-phase, and 5c exceeding rate, and to
      compare the biological aggressiveness of the proteins. Our goal was to correlate
      the degree of structural integrity and the histological grade of the injury, and
      to try to find new biological factors that would help to predict the evolution of
      disease in the salivary glands. The immunoexpression pattern of the so-called
      adhesion proteins of the salivary glands, when combined, yields important data
      about the aggressiveness of malignant neoplasms, and provides useful tools with
      which to predict the biological evolution of malignant lesions. 

PMID- 24309002
TI  - [Results of definitive radiotherapy for squamous cell carcinomas of the larynx
      patients with subglottic extension].
AB  - BACKGROUND: Squamous cell carcinoma of larynx with subglottic extension is a rare
      location described to carry a poor prognosis. The aim of this study was to
      analyze outcomes and feasibility of definitive radiotherapy in patients with
      squamous cell carcinoma. PATIENTS AND METHODS: Between 1998 and 2012, 56 patients
      with squamous cell carcinoma were treated at our institution and included in the
      analysis. Patients received definitive radiotherapy/chemoradiotherapy alone (63%)
      or after induction chemotherapy (37%) at our institute. RESULTS: The 5-year
      actuarial overall survival, progression-free survival and specific survival were
      64% (CI 95%: 48-90), 45% (CI 95%: 28-61), 88% (CI 95%: 78-98), respectively, with
      median follow-up of 74 months. The 5-year locoregional control was 69% (CI 95%:
      56-83) and the 5-year distant control was 95% (CI 95%: 89-100). There was no
      difference in overall survival and locoregional control according to front-line
      treatments or between primary subglottic cancer and glotto-supraglottic cancers
      with subglottic extension. In the multivariate analysis, performance status of at
      least 1 and positive N stage were the only predictors for overall survival
      (hazard ratio [HR] [CI 95%]: 6.5 [1.3-34; P=0.03] and 11 [1.6-75; P=0.02],
      respectively). No difference of locoregional control was observed according to
      the first received therapy. The univariate analysis retrieved that T3-T4 patients
      had a lower locoregional control (HR: 3.1; CI 95%: 1.1-9.2, P=0.04), but no
      prognostic factor was retrieved in the multivariate analysis. In patients
      receiving a larynx preservation protocol, 5-year larynx preservation rate was 88%
      (CI 95%: 78-98), and 58% in T3 patients. The 5-year larynx preservation rate was
      91% (CI 95%: 79-100) and 83% (CI 95%: 66-100) for patients who received
      radiotherapy/chemoradiotherapy or induction chemotherapy as a front-line
      treatment, respectively. CONCLUSION: This analysis suggests that the results for
      squamous cell carcinoma patients treated with radiotherapy/chemoradiotherapy are
      comparable to those obtained for other laryngeal tumors. This thus suggests the
      feasibility of laryngeal preservation protocols for infringement subglottic for
      selected cases. Further studies are needed to clarify these preliminary data.

PMID- 24309003
TI  - [Radio-induced breast morphoea: an unrecognized complication].
AB  - Morphoea is a localized scleroderma. Since the 1990s, it is described as a
      complication after irradiation for breast cancer. This complication is
      unrecognized and underdiagnosed. Irradiation seems to be a factor inducing an
      autoimmune process. Clinicians should be aware in case of an erythema in a
      treated area, appearing on average one year after the end of the irradiation.
      Histology alone can prove the diagnosis and rule out differential diagnoses:
      principally mastitis (carcinomatous, infectious), chronic radiodermatitis or
      radiation recall. Treatment of this rare complication is not consensual; it is
      most often topical steroids. The evolution is marked by a gradual decrease from
      the initial inflammation. Sclerosis persists, more or less substantially. 

PMID- 24309004
TI  - Retropharyngeal thymus and parathyroid gland: a case report.
AB  - Cervical ectopic thymus occurs when thymic tissue arrests during its embryologic
      descent through the neck to the upper mediastinum. Most often it presents as an
      asymptomatic neck mass. Rarely does it present with airway compromise,
      particularly in neonates. A neonate presented with a retropharyngeal mass causing
      dynamic upper airway obstruction, mimicking a venolymphatic malformation.
      Ultimately this proved to be aberrant ectopic thymus with an associated
      parathyroid gland. While there have been isolated reports of thymus or
      parathyroid in the retropharyngeal space, none of the prior reports found both
      within the same patient. 

PMID- 24309005
TI  - Investigation of mammographic breast density as a risk factor for ovarian cancer.
AB  - BACKGROUND: Endogenous hormones and growth factors that increase mammographic
      breast density could increase ovarian cancer risk. We examined whether high
      breast density is associated with ovarian cancer risk. METHODS: We conducted a
      cohort study of 724,603 women aged 40 to 79 years with 2,506,732 mammograms
      participating in the Breast Cancer Surveillance Consortium from 1995 to 2009.
      Incident epithelial ovarian cancer was diagnosed in 1373 women. We used partly
      conditional Cox regression to estimate the association between breast density and
      5-year risk of incident epithelial ovarian cancer overall and stratified by 10
      year age group. All statistical tests were two-sided. RESULTS: Compared with
      women with scattered fibroglandular densities, women with heterogeneously dense
      and extremely dense breast tissue had 20% and 18% increased 5-year risk of
      incident epithelial ovarian cancer (hazard ratio [HR] = 1.20, 95% confidence
      interval [CI] = 1.06 to 1.36; HR = 1.18, 95% CI = 0.93 to 1.50, respectively;
      P(trend) = .01). Among women aged 50 to 59 years, we observed a trend in elevated
      risk associated with increased breast density (P(trend) = .02); women with
      heterogeneously and extremely dense breast tissue had 30% (HR = 1.30; 95% CI =
      1.03 to 1.64) and 65% (HR = 1.65; 95% CI = 1.12 to 2.44) increased risk,
      respectively, compared with women with scattered fibroglandular densities. The
      pattern was similar but not statistically significant at age 40 to 49 years.
      There were no consistent patterns of breast density and ovarian cancer risk at
      age 60 to 79 years. CONCLUSIONS: Dense breast tissue was associated with a modest
      increase in 5-year ovarian cancer risk in women aged 50 to 59 years but was not
      associated with ovarian cancer at ages 40 to 49 or 60 to 79 years.

PMID- 24309006
TI  - Wnt signaling pathway in non-small cell lung cancer.
AB  - Wnt/beta-catenin alterations are prominent in human malignancies. In non-small
      cell lung cancer (NSCLC), beta-catenin and APC mutations are uncommon, but Wnt
      signaling is important in NSCLC cell lines, and Wnt inhibition reduces
      proliferation. Overexpression of Wnt-1, -2, -3, and -5a and of Wnt-pathway
      components Frizzled-8, Dishevelled, Porcupine, and TCF-4 is common in resected
      NSCLC and is associated with poor prognosis. Conversely, noncanonical Wnt-7a
      suppresses NSCLC development and is often downregulated. Although beta-catenin is
      often expressed in NSCLCs, it was paradoxically associated with improved
      prognosis in some series, possibly because of E-cadherin interactions.
      Downregulation of Wnt inhibitors (eg, by hypermethylation) is common in NSCLC
      tumor cell lines and resected samples; may be associated with high stage,
      dedifferentiation, and poor prognosis; and has been reported for AXIN, sFRPs 1-5,
      WIF-1, Dkk-1, Dkk-3, HDPR1, RUNX3, APC, CDX2, DACT2, TMEM88, Chibby, NKD1, EMX2,
      ING4, and miR-487b. AXIN is also destabilized by tankyrases, and GSK3beta may be
      inactivated through phosphorylation by EGFR. Preclinically, restoration of Wnt
      inhibitor function is associated with reduced Wnt signaling, decreased cell
      proliferation, and increased apoptosis. Wnt signaling may also augment resistance
      to cisplatin, docetaxel, and radiotherapy, and Wnt inhibitors may restore
      sensitivity. Overall, available data indicate that Wnt signaling substantially
      impacts NSCLC tumorigenesis, prognosis, and resistance to therapy, with loss of
      Wnt signaling inhibitors by promoter hypermethylation or other mechanisms
      appearing to be particularly important. Wnt pathway antagonists warrant
      exploration clinically in NSCLC. Agents blocking selected specific beta-catenin
      interactions and approaches to increase expression of downregulated Wnt
      inhibitors may be of particular interest. 

PMID- 24309007
TI  - Prevalence and distribution of Eimeria species in broiler chicken farms of
      different capacities.
AB  - We conducted a survey in broiler farms from Romania to establish prevalence and
      distribution of Eimeria species using single PCR assay. We found Eimeria spp. in
      21 (91%) out of 23 flocks, and in 11 (92%) out of 12 farms. Four species of
      Eimeria were identified: E. acervulina (21/23; 91%), E. tenella (14/23; 61%), E.
      maxima (5/23; 22%) and E. praecox (3/23; 13%). Infection with a single species
      (E. acervulina) was detected in 6 (26%) infected flocks originated from large
      farms. Mixed infections were found in 15 (65%) flocks and the most prevalent
      combination was E. acervulina + E. tenella (8/23; 35%). Four flocks (17%)
      harboured mixed infection with E. acervulina + E. tenella + E. maxima. E.
      acervulina was significantly more prevalent in flocks that received ionophores as
      anticoccidial feed additives.

PMID- 24309008
TI  - 13C NMR spectroscopy as a tool for the in situ characterisation of iron
      supplementing preparations.
AB  - (13)C NMR spectroscopy provides insight into the chemistry of carbohydrate-based
      ferric preparations. Specifically, it reveals whether oxygen atoms of the
      carbohydrate are directly bonded to the preparations' ferric centres or whether
      more distant interactions are present. After having validated the method by
      investigating the ferric solutions of low-molecular complexes as well as
      polynuclear ferric samples, it is demonstrated that common constituents of
      medically used ferric preparations such as sucrose and other glucose-based
      saccharides do not support ferric carbohydrate chelates. Instead, these
      carbohydrates reside outside the NMR-spectroscopically 'blinded' region about the
      ferric centres and experience the so-called Evans effect that can be used to
      measure the magnetic moment of the solutions. As a result, an easily accessible
      physicochemical parameter is provided to characterise commercial iron(III)
      preparations, namely the samples' magnetism in terms of the in situ-measured spin
      normalised effective Bohr magneton number MU(eff)(2)/35. The procedure can,
      moreover, be combined with a facile NMR-spectroscopic iron assay.

PMID- 24309009
TI  - Radioactive equilibrium: 99Mo/99mTc decay characteristics.
AB  - Within the Decay Data Evaluation Project, as an example of a radioactive
      equilibrium with isomer, the (99)Mo/(99m)Tc equilibrium mixture decay
      characteristics are examined. The results of a new decay data evaluation are
      presented for (99)Mo/(99m)Tc decay to nuclear levels in (99)Tc. These evaluated
      data have been obtained using information published up to 2013. 

PMID- 24309010
TI  - Alpha-particle emission probabilities of 236U obtained by alpha spectrometry.
AB  - High-resolution alpha-particle spectrometry was performed with an ion-implanted
      silicon detector in vacuum on a homogeneously electrodeposited (236)U source. The
      source was measured at different solid angles subtended by the detector, varying
      between 0.8% and 2.4% of 4pi sr, to assess the influence of coincidental
      detection of alpha-particles and conversion electrons on the measured alpha
      particle emission probabilities. Additional measurements were performed using a
      bending magnet to eliminate conversion electrons, the results of which coincide
      with normal measurements extrapolated to an infinitely small solid angle. The
      measured alpha emission probabilities for the three main peaks - 74.20 (5)%,
      25.68 (5)% and 0.123 (5)%, respectively - are consistent with literature data,
      but their precision has been improved by at least one order of magnitude in this
      work. 

PMID- 24309011
TI  - FT values measured to +/-0.1% for superallowed beta transitions: metrology at sub
      second time scales.
AB  - Because of angular-momentum conservation, superallowed beta decay between 0(+)
      analog states involves only the vector part of the weak interaction, so its
      measured ft value can be used to determine the vector coupling constant, G(V). If
      many such transitions are measured, then the constancy of G(V) can be established
      and several important tests made on fundamentals of the electroweak Standard
      Model. We have developed apparatus that allows us to measure half-lives to +/
      0.03% and branching ratios to +/-0.1% or better, for cyclotron-produced
      activities with half-lives as short as 100 ms. We present an overview of the
      equipment and a summary of more than 10 years of results.

PMID- 24309012
TI  - Structural adaptations of rat lateral gastrocnemius muscle-tendon complex to a
      chronic stretching program and their quantification based on ultrasound
      biomicroscopy and optical microscopic images.
AB  - BACKGROUND: A chronic regimen of flexibility training can increase range of
      motion, with the increase mechanisms believed to be a change in the muscle
      material properties or in the neural components associated with this type of
      training. METHODS: This study followed chronic structural adaptations of lateral
      gastrocnemius muscle of rats submitted to stretching training (3 times a week
      during 8weeks), based on muscle architecture measurements including pennation
      angle, muscle thickness and tendon length obtained from ultrasound biomicroscopic
      images, in vivo. Fiber length and sarcomere number per 100MUm were determined in
      3 fibers of each muscle (ex vivo and in vitro, respectively), using conventional
      optical microscopy. FINDINGS: Stretching training resulted in a significant
      pennation angle reduction of the stretched leg after 12 sessions (25%, P=0.002 to
      0.024). Muscle thickness and tendon length presented no significant changes.
      Fiber length presented a significant increase for the stretched leg (8.5%,
      P=0.00006), with the simultaneous increase in sarcomere length (5%, P=0.041)
      since the stretched muscles presented less sarcomeres per 100MUm. INTERPRETATION:
      A stretching protocol with characteristics similar to those applied in humans was
      sufficient to modify muscle architecture of rats with absence of a
      sarcomerogenesis process. The results indicate that structural adaptations take
      place in skeletal muscle tissue submitted to moderate-intensity stretching
      training.

PMID- 24309013
TI  - A controlled family study of cannabis users with and without psychosis.
AB  - BACKGROUND: Cannabis is one of the most highly abused illicit drugs in the world.
      Several studies suggest a link between adolescent cannabis use and schizophrenia.
      An understanding of this link would have significant implications for
      legalization of cannabis and its medicinal value. The present study aims to
      determine whether familial morbid risk for schizophrenia is the crucial factor
      that underlies the association of adolescent cannabis use with the development of
      schizophrenia. METHODS: Consecutively obtained probands were recruited into four
      samples: sample 1: 87 non-psychotic controls with no drug use; sample 2: 84 non
      psychotic controls with cannabis use; sample 3: 32 patients with a schizophrenia
      spectrum psychosis with no drug use; sample 4: 76 patients with schizophrenia
      spectrum psychosis with cannabis use. All cannabis using subjects used this drug
      during adolescence, and no other substance, with the exception of alcohol.
      Structured interviews of probands and family informants were used to obtain
      diagnostic information about probands and all their known relatives. RESULTS:
      There was an increased morbid risk for schizophrenia in relatives of the cannabis
      using and non-using patient samples compared with their respective non-psychotic
      control samples (p=.002, p<.001 respectively). There was no significant
      difference in morbid risk for schizophrenia between relatives of the patients who
      use or do not use cannabis (p=.43). CONCLUSIONS: The results of the current study
      suggest that having an increased familial morbid risk for schizophrenia may be
      the underlying basis for schizophrenia in cannabis users and not cannabis use by
      itself.

PMID- 24309014
TI  - Exploiting pluripotent stem cell technology for drug discovery, screening,
      safety, and toxicology assessments.
AB  - In order for the pharmaceutical industry to maintain a constant flow of novel
      drugs and therapeutics into the clinic, compounds must be thoroughly validated
      for safety and efficacy in multiple biological and biochemical systems.
      Pluripotent stem cells, because of their ability to develop into any cell type in
      the body and recapitulate human disease, may be an important cellular system to
      add to the drug development repertoire. This review will discuss some of the
      benefits of using pluripotent stem cells for drug discovery and safety studies as
      well as some of the recent applications of stem cells in drug screening studies.
      We will also address some of the hurdles that need to be overcome in order to
      make stem cell-based approaches an efficient and effective tool in the quest to
      produce clinically successful drug compounds. 

PMID- 24309016
TI  - Modified partial superficial parotidectomy versus conventional superficial
      parotidectomy improves treatment of pleomorphic adenoma of the parotid gland.
AB  - BACKGROUND: Surgical treatment of pleomorphic adenoma of the parotid gland
      remains a subject of major debate. The investigators compared postoperative
      complications and surgical parameters between modified partial superficial
      parotidectomy and conventional superficial parotidectomy. METHODS: Clinical
      records of 129 patients were reviewed and analyzed for clinical characteristics.
      RESULTS: Compared with the conventional superficial parotidectomy group, the
      modified partial superficial parotidectomy group had significantly lower rates of
      auricular numbness, Frey's syndrome, and obvious facial asymmetry (all P values
      <.05). The distance between the primary tumor capsule and satellite nodules
      ranged from .06 to 8.48 mm, and the greatest distance between the primary tumor
      capsule and satellite nodules was observed in tumors >4 cm. Furthermore,
      satellite nodules were more common in tumors >4 cm than in tumors <2 cm or tumors
      between 2 and 4 cm (all P values <.05). CONCLUSIONS: Modified partial superficial
      parotidectomy compares favorably surgically and clinically with conventional
      superficial parotidectomy in certain patients.

PMID- 24309017
TI  - To think or not to think, that is the question: individual differences in
      suppression and rebound effects in autobiographical memory.
AB  - Two studies explored the effects of forget instructions on autobiographical
      memory at immediate test and following delays of either 12-13 months, or 3-4
      months. Using the Autobiographical Think/No-Think procedure (cf., Noreen &
      MacLeod, 2013), 24 never-depressed participants (Study 1) first generated 12
      positive and 12 negative autobiographical memories and associated cues.
      Participants were then asked to recall the memory associated with some of the
      cues (i.e., 'think' condition), or to avoid saying or thinking about the memory
      associated with other cues (i.e., 'no-think' condition). Participants were then
      asked to recall the memories associated with all the cues at immediate test and
      following a delay of 12-13 months. Participants were found to be successful at
      forgetting both positive and negative autobiographical memories following 'no
      think' instructions at immediate test but this forgetting effect did not persist
      following a 12-13 month delay. This pattern of remembering and forgetting was
      replicated in a second study (using 27 never-depressed participants) following a
      3-4 month delay. Participants who had been less successful at forgetting 'no
      think' memories at immediate test, were more likely to show rebound effects for
      those memories following a delay compared to memories which received neither
      'think' nor 'no-think' instructions. Individual differences in inhibitory control
      and the efficacy of potential therapeutic interventions of 'no-think'
      instructions are considered.

PMID- 24309019
TI  - A high-throughput fluorescence anisotropy-based assay for human topoisomerase II
      beta-catalyzed ATP-dependent supercoiled DNA relaxation.
AB  - Because of their essentiality for DNA replication, transcription, and repair,
      type II topoisomerases are targets for antibacterial and anticancer drugs. There
      are two type II topoisomerases in humans, topoisomerase IIalpha (TOP2A) and
      topoisomerase IIbeta (TOP2B), and two in bacteria, gyrase and topoisomerase IV.
      Inhibition of one or both of the human type II topoisomerases by antibacterial
      compounds targeting their bacterial counterparts could result in toxicity. In
      addition, side effects of anticancer drugs targeting TOP2A could result from
      inhibition of TOP2B. A simple and rapid biochemical assay for the activity of
      TOP2A and TOP2B would be advantageous for screening for novel inhibitors, testing
      them for selectivity for one enzyme over the other, and testing for potential
      toxicity of antibacterial type II topoisomerases mediated by human topoisomerase
      II inhibition. In this paper, we show that a previously reported high-throughput,
      fluorescence anisotropy-based assay for ATP-dependent relaxation of supercoiled
      DNA by human TOP2A can also be used under identical conditions for human TOP2B.
      We used this assay to compare the potencies versus both enzymes of 19 compounds
      reported in the literature to inhibit human and/or bacterial type II
      topoisomerases. We also used the assay to investigate the effect of ATP
      concentration on inhibitor potencies. 

PMID- 24309018
TI  - Heparan sulfate in the nucleus and its control of cellular functions.
AB  - Heparan sulfate proteoglycans (HSPG) are present on the cell surface, within the
      extracellular matrix, and as soluble molecules in tissues and blood. HSPGs are
      known to regulate a wide range of cellular functions predominantly by serving as
      co-receptors for growth factors, chemokines, and other regulatory proteins that
      control inflammation, wound healing and tumorigenesis. Several studies have
      demonstrated the presence of heparan sulfate (HS) or HSPGs in the cell nucleus,
      but little attention has been focused on their role there. However, evidence is
      mounting that nuclear HS and HSPGs have important regulatory functions that
      impact the cell cycle, proliferation, transcription and transport of cargo to the
      nucleus. The discovery of proteoglycans in the nucleus extends the list of "non
      traditional nuclear proteins" that includes, for example, cytoskeletal proteins
      such as actin and tubulin, and growth factors and their receptors. In this review
      we discuss the discovery and fascinating roles of HS and HSPGs in the nucleus and
      propose a number of key questions that remain to be addressed. 

PMID- 24309015
TI  - In vitro models of tumor vessels and matrix: engineering approaches to
      investigate transport limitations and drug delivery in cancer.
AB  - Tumor-stroma interactions have emerged as critical determinants of drug efficacy.
      However, the underlying biological and physicochemical mechanisms by which the
      microenvironment regulates therapeutic response remain unclear, due in part to a
      lack of physiologically relevant in vitro platforms to accurately interrogate
      tissue-level phenomena. Tissue-engineered tumor models are beginning to address
      this shortcoming. By allowing selective incorporation of microenvironmental
      complexity, these platforms afford unique access to tumor-associated signaling
      and transport dynamics. This review will focus on engineering approaches to study
      drug delivery as a function of tumor-associated changes of the vasculature and
      extracellular matrix (ECM). First, we review current biological understanding of
      these components and discuss their impact on transport processes. Then, we
      evaluate existing microfluidic, tissue engineering, and materials science
      strategies to recapitulate vascular and ECM characteristics of tumors, and finish
      by outlining challenges and future directions of the field that may ultimately
      improve anti-cancer therapies. 

PMID- 24309020
TI  - A versatile spectrophotometric protein tyrosine phosphatase assay based on 3
      nitrophosphotyrosine containing substrates.
AB  - A versatile assay for protein tyrosine phosphatases (PTP) employing 3
      nitrophosphotyrosine containing peptidic substrates is described. These
      therapeutically important phosphatases feature in signal transduction pathways.
      The assay involves spectrophotometric detection of 3-nitrotyrosine production
      from 3-nitrophosphotyrosine containing peptidic substrates, which are accepted by
      many PTPs. Compared to conventional chromogenic phosphate derivatives, the more
      realistic peptidic substrates allow evaluating substrate specificity. The assay's
      applicability is demonstrated by determining kinetic parameters for several PTP
      substrate combinations and inhibitor evaluation, as well as detection of PTP
      activity in lysates. The convenient new assay may assist further adoption of PTPs
      in drug development. 

PMID- 24309021
TI  - Direct transmission of the cat flea (Ctenocephalides felis) between cats
      exhibiting social behaviour.
AB  - A study design was created to assess the potential for fleas to infest cats
      directly from other cats. In the first experiment, six cats were infested with
      100 fleas each and then immediately put in contact with six flea-free cats for 24
      h. After removal of all fleas the study was repeated and the contact between cats
      lasted 48 h. The total numbers of fleas recovered out of the 600 fleas deposited
      on the 6 donor cats after each infestation were 499 and 486 at 24 h and 48 h
      respectively. At 1 h post-contact, five fleas were found on the receiver cats,
      with three cats having one flea and one cat, two fleas. The number of fleas
      recovered on receiver cats increased towards the end of the study. At 24 h, 20%
      of the fleas were found on the receiver cats, and at 48 h, 23%. In a second
      experiment, the six flea-free cats were put in contact with the six donor cats
      which were each infested by 100 fleas 48 h before. Fewer fleas were found on the
      receiver cats (n = 15), representing 3.8% of all fleas recovered (n = 403). All
      the observed fleas had fed. The fleas collected on receiving cats comprised 10
      males and 5 females, and 4 of the 5 females were engorged and contained eggs. The
      fleas collected on donor cats comprised 153 males and 235 females, they were all
      fed and all females contained eggs. This experiment demonstrated that gravid
      female fleas have a tendency to become permanently but not exclusively parasitic.
      Nevertheless, a few can change their cat host in as little as 1 h, which may play
      a role in the rapid introduction of a new flea population into a cat environment.

PMID- 24309022
TI  - Lactobacillus Reuteri for the prevention of necrotising enterocolitis in very low
      birthweight infants: a randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effect of oral Lactobacillus reuteri (L reuteri) first
      on the incidence and severity of Necrotising enterocolitis (NEC) and second on
      sepsis. DESIGN: Prospective randomised controlled study. SETTING: Tertiary
      neonatal intensive care unit. PATIENTS AND INTERVENTIONS: Preterm infants with a
      gestational age of <=32 weeks and a birth weight of <=1500 g were included
      (n=400). Infants in the first group were given 100 million CFU/day (5 drops) of
      lyophilised L reuteri (DSM 17938) mixed in breast milk or formula, starting from
      first feeding until discharge. Participants in the control group were given a
      placebo. MAIN OUTCOME MEASURES: To determine and compare the frequency of NEC
      and/or death after 7 days, frequency of proven sepsis, rates of feeding
      intolerance and duration of hospital stay. RESULTS: There was no statistically
      significant difference between groups in terms of frequency of NEC stage >=2 (4%
      vs 5%; p=0.63) or overall NEC or mortality rates (10% vs 13.5%; p=0.27).
      Frequency of proven sepsis was significantly lower in the probiotic group
      compared to the control group (6.5% vs 12.5%; p=0.041). A significant difference
      was also observed with regard to rates of feeding intolerance (28% vs 39.5%;
      p=0.015) and duration of hospital stay (38 (10-131) vs 46 (10-180) days;
      p=0.022). CONCLUSIONS: Our results show that oral L reuteri does not seem to
      affect the overall rates of NEC and/or death in preterm infants followed up in
      the neonatal intensive care unit, and significant reductions were observed in the
      frequency of proven sepsis, rates of feeding intolerance and duration of hospital
      stay. TRIAL REGISTRATION NUMBER: NCT01531179.

PMID- 24309023
TI  - Human milk feeding.

PMID- 24309024
TI  - [Role of imaging procedures in the diagnosis of synchronous bilateral breast
      cancer].
AB  - OBJECTIVE: To investigate the role of imaging procedures in the diagnosis of
      synchronous bilateral breast cancer (SBBC) PATIENTS AND METHODS: The patient
      group consisted of consecutive women undergoing managed for SBBC in our
      institution between January 2006 and July 2012. We defined SBBC as bilateral
      breast tumors diagnosed simultaneously or up to 3 months after initial diagnosis.
      Clinical data included comorbidities, BMI (kg/m(2)), preoperative breast imaging
      modalities used and their findings. RESULTS: Of the 2322 patients with newly
      diagnosed breast cancer treated on the study period, 46 patients with the
      diagnosis of SBBC were enrolled to the study. A total of 41.3% patients had
      family history of breast cancer. A total of 56.52% had clinical symptoms. The
      most frequent situation of diagnosis (32.6%) was the association of a palpable
      tumor and a contralateral radiologic abnormality. MRI permitted the diagnosis of
      19.6% occult contralateral lesions. DISCUSSION AND CONCLUSION: Clinical
      examination and conventional imaging procedures (mammography and sonography)
      detects the majority (76%) of synchronous contralateral breast cancers. A family
      history of breast cancer, a multifocal breast tumor or the presence of an
      invasive lobular carcinoma should be arguments for the realization of a breat MRI
      to eliminate contralateral malignancy.

PMID- 24309025
TI  - [Lowe syndrome revealed by prenatal diagnosis of congenital cataract with brain
      abnormalities].
AB  - Congenital cataract is a rare disease whose incidence is estimated to 0.5% of
      birth in France. A study of the literature shows that congenital cataract is
      idiopathic in 50% of cases, hereditary forms representing 25% of cases. Other
      causes of congenital cataract are represented by viral embryofoetopathies
      acquired during pregnancy, metabolic disorders and chromosomal aberrations within
      the scope of malformative syndromes. The authors report the case of a neonatal
      diagnosis of Lowe syndrome suspected by the discovery of bilateral cataract
      initially isolated. The morphological exploration was completed by secondary
      brain abnormalities (periventricular lesions). The etiological prenatal
      exploration was negative. Lowe syndrome is a rare cause of antenatal cataract,
      which so far only one case has been reported. 

PMID- 24309026
TI  - [Metastatic breast cancer to the stomach: An uncommon evolution of breast
      carcinoma].
AB  - Breast carcinoma exceptionally leads to metastatic linitis plastica.
      Distinguishing a breast cancer metastasis to the stomach from a primary gastric
      cancer on the basis of clinical and radiological signs is very challenging.
      Thanks to being cognizant of the previous history of invasive lobular carcinoma
      and the gastric biopsy followed by immunohistochemical analysis, gastric
      metastasis can be diagnosed. Despite the use of chemotherapy and hormonal
      therapy, gastric metastasis remains often associated with poor prognosis. We
      present a case where gastric biopsy allowed a metastatic breast cancer to the
      stomach to be diagnosed and we discuss its clinical, diagnostic, pathological and
      therapeutic particularities.

PMID- 24309027
TI  - [Pertinence of the preoperative exploration in the evaluation of the risk of
      lymph node metastasis in endometrial cancer].
AB  - PURPOSE: To assess the relevance of MRI, endometrial biopsy and curettage in the
      diagnosis of endometrial cancer at high risk of lymph node metastasis. PATIENTS
      AND METHODS: A retrospective study on continuous series of patients treated for
      endometrial cancer limited to the uterus between 2004 and 2008, results of
      preoperative evaluation of tumor stage using MRI, histological type and grade by
      endometrial curettage and biopsies were compared to final histological
      examination. RESULTS: One hundred and sixty-nine patients were included in the
      study. Ninety (53.3%) had MRI, 112 (66.2%) curettage and 61 (36.6%) endometrial
      biopsy using Pipelle de Cornier. Sensibility (SN), specificity (SP), positive
      (PPV) and negative predictive values (NPV) of MRI, in the diagnosis of
      endometrial cancer at high risk of lymph nodes metastases were of 65.6%, 87.2%,
      77.7%, 79.2%. For EB and curettage SN, SP, PPV and NPV were of 42.9%, 96.9%, 85%,
      79.5%; 80.6%, 98.3%, 96.2% and 90.6% respectively. 37.8% of cancers diagnosed to
      be at low risk of lymph node metastasis were at high risk in definitive
      histologic examination. DISCUSSION AND CONCLUSION: Preoperative evaluation by
      MRI, endometrial curettage and biopsy has good diagnostic value in the
      identification of endometrial cancer susceptible to benefit from lymphadenectomy.
      Underestimation, however, is encountered in approximately one third of cases.

PMID- 24309028
TI  - [Quality process and risk of cons-productivity].

PMID- 24309029
TI  - [Cervical pessary and prevention of preterm birth].
AB  - Cervical pessary is a promising tool to prevent preterm birth in high risk
      pregnant women with shortened midtrimester ultrasonographic cervical length. It
      is well tolerated by women. PECEP and ProTWIN trials have opened new fields of
      clinical research. Their results suggest that cervical pessary may prevent
      preterm birth in women with (i) singleton and cervical length <=25 mm at 18
      22weeks, and with (ii) twins and cervical length <=37mm at 16-22weeks. These
      results must be confirmed by other randomized controlled trial before a
      generalization of cervical pessary in these situations. The role of cervical
      pessary in the existing strategies to prevent birth (progesterone, cerclage or
      combinations thereof) has to be determined.

PMID- 24309030
TI  - [Ultrasound screening and diagnostic ultrasound: should we revise the
      classification of examinations?].

PMID- 24309031
TI  - [Prognostic value of early hCG changes after methotrexate injection for ectopic
      pregnancy].
AB  - OBJECTIVES: The purpose of this study was to evaluate the predictive value of
      early hCG changes on the risk of methotrexate (MTX) therapy failure for ectopic
      pregnancy. PATIENTS AND METHODS: This monocentric observational study compared
      the success of single-dose MTX therapy according to early hCG changes. Patients
      with a decrease of hCG value by at least 20% between day 1 and day 4 were
      followed up one month later only with an hCG concentration (group A, study
      protocol). The others patients were followed up with classic protocol, one time a
      week (group B). RESULTS: Of the 91 patients treated, there were 29 (31.9%)
      patients in the group A and 62 (68.1%) in the group B. The overall success rate
      of MTX treatment was 89%. The success rate of single-dose MTX therapy was
      significantly increased in group A (29/29 (100%) vs 30/62 (48.4%), P<0.001). The
      rate of patients requiring surgical treatment was significantly lower in group A
      (0/29 vs 10/62 (16%), P=0.02) (Table 1). CONCLUSION: The 20%-decrease cut-off
      between day 1 and day 4 appears to be a predictive factor to select patients with
      low failure rate after one MTX injection, allowing a less stringent follow-up.

PMID- 24309032
TI  - [Abruptio placentae. Diagnosis, management and maternal-fetal prognosis: a
      retrospective study of 100 cases].
AB  - OBJECTIVES: To update knowledge on placental abruption because there are few
      recent series published although the perinatal care has progressed. PATIENTS AND
      METHODS: A retrospective observational study has been conducted on 100
      consecutive cases of abruptio placentae, occurring from January 2008 to June
      2011, in the two maternity units of the University Hospital of Strasbourg
      (France). RESULTS: One hundred and five births among which five twin pregnancies
      were included. Clinical context was evident in 91% of cases, but the classic
      clinical triad was present in only 4% of cases. Clots were found at immediate
      placenta examination in 77% of cases. Pathological diagnosis was directly in
      accordance with clinical diagnosis in half the cases. Mean date of childbirth was
      33 weeks of amenorrhea and 6 days. Sixty-seven patients gave birth prematurely.
      Among them, 50 patients delivered before 34 weeks. Sixty caesareans were
      performed in emergency before labor, including 47 with general anesthesia. Twelve
      patients had post-partum haemorrhage and ten coagulation disorders. There was no
      maternal death. Perinatal mortality was 19% with 13 fetal deaths in utero
      (12.4%), four children born in an apparent death state with resuscitation failure
      (3.8%) and three neonatal deaths (2.8%). DISCUSSION AND CONCLUSION: Placental
      abruption is a serious and unpredictable situation. Joint medical care of
      obstetricians and intensivists is often required. Perinatal mortality mainly
      occurs in utero.

PMID- 24309036
TI  - Lateral window sinus elevation technique: managing challenges and complications.
AB  - Sinus floor elevation is commonly used in cases where alveolar bone resorption
      has led to insufficient bone height for the placement of dental implants. Lateral
      wall sinus elevation is carried out when the bone is severely deficient. Although
      this procedure has a high rate of success, it may present surgical problems. A
      description of the anatomy of the maxillary sinus and lateral wall augmentation
      techniques leads to a discussion of the various challenges and complications that
      may arise and their management. 

PMID- 24309033
TI  - Assessment of appendicular skeletal muscle mass by bioimpedance in older
      community-dwelling Korean adults.
AB  - It is crucial to investigate age-related body composition changes in geriatric
      medicine. Bioelectrical impedance analysis (BIA) is easy to perform, non
      invasive, relatively inexpensive, and portable. However, the accuracy of
      measurement by BIA is questionable. To develop and cross-validate the predictive
      equation for estimated appendicular skeletal muscle mass (ASM) using BIA in older
      community-dwelling Korean adults, we include two cohorts: study participants aged
      65-80 years in the Ansung cohort for the Korean Health and Genome Study (men,
      n=285; women, n=435) used as equation-generating group, and Korean Longitudinal
      Study of Health Aging (KLoSHA) as cross-validation group (men, n=202; women,
      n=208). Dual energy X-ray absorptiometry (DXA) and BIA were performed in both
      cohorts. Using multiple linear regression analysis, we drew a predictive equation
      for DXA-measured ASM by BIA resistance. From DXA and BIA measurements in the
      Ansung cohort, we generated the estimated equation ASM
      (kg)=[(Ht(2)/R*0.104)+(age*-0.050)+(gender*2.954)+(weight*0.055)]+5.663 where Ht
      is height in centimeters; R is BIA resistance in 250Omega; for gender, men=1 and
      women=0; and age is in years. We validated this equation in the KLoSHA. The r(2)
      of the estimated ASM was 0.890. This BIA equation provides valid estimates of ASM
      in older Korean adults. 

PMID- 24309037
TI  - Maintaining perspective on third molar extraction.
AB  - Third molar extraction is one of the most common oral surgeries performed on
      Canadian patients, particularly young adults. Vigorous debate persists about the
      risks of retention of asymptomatic impacted third molars, compared to extraction.
      The controversy centres on whether medical necessity justifies the cost of third
      molar extraction for the patient in terms of substantial pain and potential loss
      of income during recovery and for the federal or provincial health care systems,
      which may be billed for a portion of the surgical fees. Several research studies
      initiated by the American Association of Oral and Maxillofacial Surgeons (AAOMS)
      report new associations between oral disease and asymptomatic impacted third
      molars. These findings merit careful attention because they are being used by the
      AAOMS to advocate for prophylactic third molar extraction--an approach that
      contradicts the conclusions of a Canadian health technology report, American
      Public Health Association policy, and health technology reports from Sweden,
      Belgium and the UK. The decision to extract third molars seems most effective
      when made on a case-by-case basis that is tailored to each patient's health
      status and access to professional oral health care.

PMID- 24309038
TI  - Alternative interim treatment for single-tooth loss and diastema: two clinical
      reports.
AB  - Wide diastema can be a challenge when the patient demands rapid, conservative
      treatment. New adhesive materials and techniques provide several options for
      tooth replacement. This article describes 2 cases that illustrate successful
      rehabilitation of edentulous spaces with artificial porcelain teeth and glass
      fibre.

PMID- 24309039
TI  - Managing a patient with a lost retainer or completely debonded appliance.

PMID- 24309040
TI  - Management of a necrotic tooth with unstoppable drainage.

PMID- 24309041
TI  - Managing patients with oral candidiasis.

PMID- 24309042
TI  - The "mobile microbiome": journey beyond the mouth.
AB  - An article published in the Journal of Dental Research (JDR) reviews the latest
      contributions to dentistry's understanding of the "oral health, total health"
      concept. We asked Dr. Christopher McCulloch, professor and director of the Matrix
      Dynamics Group at the University of Toronto's faculty of dentistry, for his
      perspectives on the paper

PMID- 24309043
TI  - Fixed orthodontic appliances in the management of severe dental trauma in mixed
      dentition: a case report.
AB  - We describe a case of complex trauma to the early mixed dentition in which tooth
      avulsion, intrusion, extrusion and lateral luxation were managed effectively
      using a fixed, non-rigid orthodontic splint after treatment with a traditional
      wire-composite splint had failed. The use of orthodontic brackets and flexible
      wires provided several advantages, such as the ability to splint severely
      malpositioned teeth; easy assessment without removing the splint; slow, gentle
      repositioning of traumatized teeth; and gradual reestablishment of the arch form
      allowing for ease of future prosthodontic rehabilitation. Therefore, orthodontic
      appliances should be considered as a viable option for managing complex dental
      trauma. 

PMID- 24309044
TI  - The endocrown: a different type of all-ceramic reconstruction for molars.
AB  - The endocrown is indicated for the endodontic restoration of severely damaged
      molars. This monolithic, ceramic adhesive restoration requires specific
      preparation techniques to satisfy criteria that are primarily biomechanical in
      nature: a cervical margin in the form of a butt joint and a preparation of the
      pulp chamber that does not extend into the root canals. The remaining tooth
      substance is thus more robust, resulting in increased longevity. This simple and
      efficient concept is compatible with the philosophy of biointegrated prostheses.
      This type of reconstruction, which is still uncommon, should be more widely known
      and used. 

PMID- 24309045
TI  - Re: falling short in organized dentistry: a call for increased diversity.

PMID- 24309046
TI  - Success story: recognizing oral health research.

PMID- 24309047
TI  - Plugged in: social media in the dental profession.

PMID- 24309048
TI  - Minor oral surgery in fasting Muslim patients during Ramadan.

PMID- 24309049
TI  - Preserving alveolar bone growth following cervical root fracture: a case report.
AB  - Root fracture injuries affect 0.5%-7% of permanent teeth. Although cervical root
      fractures are less frequent in children, their serious consequences and poor
      prognosis may lead to tooth loss. In this case presentation, we discuss a
      treatment approach chosen to preserve alveolar bone growth following a cervical
      root fracture in an 8-Year-old boy. 

PMID- 24309050
TI  - Helping the Lac-Megantic community grieve.

PMID- 24309051
TI  - Do amalgam fillings affect mercury levels in urine? A Canadian study.

PMID- 24309052
TI  - Managing a patient with pericoronitis.

PMID- 24309053
TI  - CTX as a marker for BRONJ.

PMID- 24309054
TI  - The author responds.

PMID- 24309055
TI  - Many middle-income earners can't afford dental care in Canada.

PMID- 24309056
TI  - Study examines bacteria's effect on composite restorations.

PMID- 24309057
TI  - A dentist recognizes ectodermal dysplasia and brings welcome relief to family.

PMID- 24309058
TI  - Plugged in: advice for Windows XP users.

PMID- 24309062
TI  - Taste disorders: a review.
AB  - Taste disorders are distressing for patients. They can also pose a serious threat
      to the health of older and more vulnerable patients, who can become malnourished
      through a loss of taste or changes in taste perception. Despite the profound
      impact of taste changes on health, the literature on their diagnosis,
      pathogenesis and treatment is sparse. Taste changes, including the experience of
      unexplained foul tastes or a decrease in taste sensations, may lead patients to
      seek out inappropriate dental treatments, but such treatments are often
      unsuccessful in resolving the complaint. Correct diagnosis of taste loss is the
      first step in the treatment of taste abnormalities and the avoidance of
      unnecessary dental treatment. It is therefore helpful for both patient and health
      care provider to be aware of the causes of taste changes. This review presents an
      overview of the causes, diagnosis and management of taste abnormalities. 

PMID- 24309063
TI  - Managing patients with red or red-white oral lesions.

PMID- 24309064
TI  - Managing patients with primary incisor root fracture.

PMID- 24309065
TI  - GOAL: an inverse toxicity-related algorithm for daily clinical practice decision
      making in advanced kidney cancer.
AB  - Metastatic renal cell carcinoma (mRCC), considered almost an orphan disease only
      six years ago, appears today a very dynamic pathology. The recently switch to the
      actual overcrowded scenario defined by seven active drugs has driven physicians
      to an incertitude status, due to difficulties in defining the best possible
      treatment strategy. This situation is mainly related to the absence of predictive
      biomarkers for any available or new therapy. Such issue, associated with the
      nearly absence of published face-to-face studies, draws a complex picture frame.
      In order to solve this dilemma, decisional algorithms tailored on drug efficacy
      data and patient profile are recognized as very useful tools. These approaches
      try to select the best therapy suitable for every patient profile. On the
      contrary, the present review has the "goal" to suggest a reverse approach: basing
      on the pivotal studies, post-marketing surveillance reports and our experience,
      we defined the polarizing toxicity (the most frequent toxicity in the light of
      clinical experience) for every single therapy, creating a new algorithm able to
      identify the patient profile, mainly comorbidities, unquestionably unsuitable for
      each single agent presently available for either the first- or the second-line
      therapy. The GOAL inverse decision-making algorithm, proposed at the end of this
      review, allows to select the best therapy for mRCC by reducing the risk of
      limiting toxicities. 

PMID- 24309066
TI  - General in-situation safety behaviors are uniquely associated with post-event
      processing.
AB  - BACKGROUND AND OBJECTIVES: Research suggests that state anxiety and in-situation
      safety behaviors are associated with post-event processing (PEP) in social
      anxiety. Past research has obtained mixed results on whether one or both factors
      contribute to PEP. The current investigation evaluated state anxiety and in
      situation safety behaviors (including subtypes of in-situation safety behaviors)
      simultaneously to determine their relative contributions to PEP. METHODS: A
      prospective study assessed social anxiety, state anxiety, in-situation safety
      behaviors, PEP, and depression in the context of a speech stressor. RESULTS:
      Consistent with theory, in-situation safety behaviors were uniquely associated
      with greater PEP. State anxiety was not uniquely associated with PEP.
      Furthermore, restricting and active subtypes of in-situation safety behaviors
      showed specificity to PEP. LIMITATIONS: Limitations of the present study include
      the use of a nonclinical analog sample and retrospective reporting of PEP.
      CONCLUSIONS: These findings highlight the importance of research on in-situation
      safety behaviors as a potential contributor to PEP.

PMID- 24309067
TI  - Rapid multi-field T(1) estimation algorithm for Fast Field-Cycling MRI.
AB  - Fast Field-Cycling MRI (FFC-MRI) is an emerging MRI technique that allows the
      main magnetic field to vary, allowing probing T1 at various magnetic field
      strengths. This technique offers promising possibilities but requires long scan
      times to improve the signal-to-noise ratio. This paper presents an algorithm
      derived from the two-point method proposed by Edelstein that can estimate T1
      using only one image per field, thereby shortening the scan time by a factor of
      nearly two, taking advantage of the fact that the equilibrium magnetisation is
      proportional to the magnetic field strength. Therefore the equilibrium
      magnetisation only needs measuring once, then T1 can be found from inversion
      recovery experiments using the Bloch equations. The precision and accuracy of the
      algorithm are estimated using both simulated and experimental data, by Monte
      Carlo simulations and by comparison with standard techniques on a phantom. The
      results are acceptable but usage is limited to the case where variations of the
      main magnetic field are fast compared with T1 and where the dispersion curve is
      relatively linear. The speed-up of T1-dispersion measurements resulting from the
      new method is likely to make FFC-MRI more acceptable when it is applied in the
      clinic. 

PMID- 24309068
TI  - Adequate dietary vitamin D and calcium are both required to reduce bone turnover
      and increased bone mineral volume.
AB  - Clinical studies indicate that the combination of vitamin D and dietary calcium
      supplementation is more effective for reducing fracture risk than either
      supplement alone. Our previous dietary studies demonstrated that an adequate
      serum 25-hydroxyvitamin D3 (25D) of 80nmol/L or more reduces bone RANKL
      expression, osteoclastogenesis and maintains the optimal levels of trabecular
      bone volume (BV/TV%) in young rats. The important clinical question of the
      interaction between vitamin D status, dietary calcium intake and age remains
      unclear. Hence, 9 month-old female Sprague-Dawley rats (n=5-6/group) were pair
      fed a semi-synthetic diet containing varying levels of vitamin D (0, 2, 12 or
      20IU/day) and dietary calcium (0.1% or 1%) for 6 months. At 15 months of age,
      animals were killed, for biochemical and skeletal analyses. While changes to
      serum 25D were determined by both dietary vitamin D and calcium levels, changes
      to serum 1,25-dihydroxyvitamin D3 (1,25D) were consistently raised in animals fed
      0.1% Ca regardless of dietary vitamin D or vitamin D status. Importantly, serum
      cross-laps levels were significantly increased in animals fed 0.1% Ca only when
      combined with 0 or 2 IUD/day of vitamin D, suggesting a contribution of both
      dietary calcium and vitamin D in determining bone resorption activity. Serum
      25(OH)D3 levels were positively correlated with both femoral mid-diaphyseal
      cortical bone volume (R(2)=0.24, P<0.01) and metaphyseal BV/TV% (R(2)=0.23,
      P<0.01, data not shown). In multiple linear regressions, serum 1,25(OH)2D3 levels
      were a negative determinant of CBV (R(2)=0.24, P<0.01) and were not a determinant
      of metaphyseal BV/TV% levels. These data support clinical data that reduced bone
      resorption and increased bone volume can only be achieved with adequate 25D
      levels in combination with high dietary calcium and low serum 1,25D levels. This
      article is part of a Special Issue entitled '16th Vitamin D Workshop'. 

PMID- 24309069
TI  - Trypanosoma (Megatrypanum) lainsoni n. sp. from Mesomys hispidus (Rodentia:
      Echimyidae) in Brazil: trypomastigotes described from experimentally infected
      laboratory mice.
AB  - We report the detection, isolation and description of Trypanosoma (Megatrypanum)
      lainsoni n. sp. from a caviomorph rodent, Mesomys hispidus (Rodentia:
      Echimyidae), obtained in the Rio Negro region of the state of Amazonas, in
      northern Brazil. Laboratory-bred white mice (Mus musculus) and rats (Rattus
      rattus) were inoculated with large numbers of culture forms by intraperitoneal
      route, and trypomastigotes appeared in their blood 3-8 days post-inoculation. One
      single epimastigote was also found in Mus musculus. Similar attempts to infect
      Rattus norvegicus, hamsters (Mesocricetus auratus), the opossum Didelphis
      marsupialis, the anteater Tamandua tetradactyla and triatomine bugs were
      unsuccessful, following six months of observations and microscopic examinations
      of blood films and blood cultures. As we have found no previous record of a
      Trypanosoma (Megatrypanum) species naturally infecting a member of the family
      Echimyidae, or any other caviomorph rodent, we conclude that this is the first
      time such an infection has been reported. The new species is unusual in the
      subgenus for its infectivity to laboratory mice. 

PMID- 24309070
TI  - Proactive coping poststroke: psychometric properties of the Utrecht Proactive
      Coping Competence Scale.
AB  - OBJECTIVE: To examine psychometric properties of the Utrecht Proactive Coping
      Competence scale (UPCC) and explore relations of proactive coping with health
      related quality of life (HRQOL) and characteristics of patients with stroke.
      DESIGN: Cross-sectional study. Reliability and convergent validity, and
      associations with HRQOL and characteristics of patients with stroke were
      examined. SETTING: Inpatient and outpatient settings of hospitals and
      rehabilitation centers in The Netherlands. PARTICIPANTS: Patients with stroke
      (N=55; mean age, 58.7+/-12.8y; mean months since stroke, 25.0+/- 38.5).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: UPCC, Utrecht Coping List
      (UCL), and the short Stroke Specific Quality of Life scale (SS-QOL-12). RESULTS:
      The UPCC showed excellent reliability (Cronbach's alpha=.95) without
      floor/ceiling effects or skewed score distribution. Convergent validity was shown
      by moderate positive relations with the UCL subscale active problem solving
      (r=.38) and moderate negative relations with the UCL subscales passive reactions
      (r=-.50), avoidance (r=-.40), and expression of emotions (r=-.42). Correlations
      between the UPCC and HRQOL domains were moderate to strong (r=.48-.61) and
      stronger than those between UCL subscales and HRQOL domains. The only
      characteristic of patients with stroke associated with proactive coping was time
      after stroke (r=-.52). CONCLUSIONS: The UPCC appears reliable and valid for
      patients with stroke. Moreover, we found positive associations between proactive
      coping and HRQOL. Future research is recommended to confirm our results and to
      explore ways to enhance proactive coping in patients with stroke.

PMID- 24309071
TI  - Self-scoring templates for motor and cognitive subscales of the FIM instrument
      for persons with spinal cord injury.
AB  - OBJECTIVE: To provide self-scoring templates for the FIM instrument's motor and
      cognitive scales that enable clinicians to monitor progress during rehabilitation
      using equal-interval Rasch-calibrated measures instead of ordinal raw scores.
      DESIGN: Secondary analysis of a prospective, observational cohort study. SETTING:
      Six geographically dispersed hospital-based rehabilitation centers in the United
      States. PARTICIPANTS: Subset of consecutively enrolled individuals with new
      traumatic spinal cord injuries discharged from participating rehabilitation
      centers (N=1146). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Subscores
      of the FIM instrument, including a 13-item motor scale, a 5-item cognitive scale,
      an 11-item (without sphincter control items) motor scale, a 3-item transfer
      scale, a 6-item self-care scale, a 3-item self-care upper extremity scale, and a
      3-item self-care lower extremity scale. RESULTS: KeyForms for the FIM instrument
      scales allow clinicians and investigators to estimate patients' functional status
      and monitor progress. In cases with no missing data, the look-up tables provide
      more accurate estimates of patients' functional status. CONCLUSION: Clinicians
      can use KeyForms and look-up tables for FIM instrument subscales to monitor
      patients' progress and communicate improvement in equal-interval units.

PMID- 24309072
TI  - Effect of chemodenervation of the rectus femoris muscle in adults with a stiff
      knee gait due to spastic paresis: a systematic review with a meta-analysis in
      patients with stroke.
AB  - OBJECTIVE: To determine the effect of motor branch block (MBB) or neuromuscular
      block (NMB) of the rectus femoris on knee kinematics during swing, functional
      outcome, and energy cost in adults with spastic paresis presenting a stiff knee
      gait. DATA SOURCES: PubMed, Embase, CINAHL, and Cochrane Library were searched.
      Studies were collected up to February 26, 2013. Reference lists were additionally
      scrutinized. STUDY SELECTION: No restrictions were applied regarding study
      design. Patients were adults suffering from a central neurological disorder.
      Interventions had to include MBB or NMB. Outcome measures had to include knee
      kinematics during the swing phase. Study selection was independently performed by
      2 reviewers. DATA EXTRACTION: Two reviewers independently assessed the
      methodological quality of included studies. Data on kinematics, functional
      outcome, and energy cost from patients with stroke were extracted from the total
      population and when possible pooled. DATA SYNTHESIS: A total of 9 articles
      describing 12 different studies were included. Knee kinematics (peak knee flexion
      or knee range) during swing improved significantly in all the included studies.
      The average increase in peak knee flexion varied from 1.9 degrees  to 15.4
      degrees . Data pooling of peak knee flexion in patients with stroke showed a
      significant improvement of 7.37 degrees  (P=.000) in NMB studies and of 9.35
      degrees  (P=.002) in MBB studies. Data pooling of knee velocity at toe-off showed
      a significant improvement of 53.01 degrees /s in NMB studies. In MBB studies,
      this improvement was not significant. Data pooling of knee range of motion,
      functional outcomes, and energy cost showed no significant difference.
      CONCLUSIONS: According to this review, chemodenervation of the rectus femoris
      shows a significant improvement in peak knee flexion during swing. The effect on
      functional outcomes and energy cost is still unclear.

PMID- 24309073
TI  - Trend breaks in incidence of non-cardia gastric cancer in the Netherlands.
AB  - INTRODUCTION: The incidence of gastric cancer declined over the past decades.
      Recently, unfavorable trend breaks (i.e. rise in incidence) were seen for non
      cardia cancer in younger age groups in the US. It is unclear whether these also
      occur in other Western countries. We aimed to analyze the gastric cancer
      incidence trends by age, sex, subsite and stage in the Netherlands. METHODS: Data
      on all patients with gastric adenocarcinoma diagnosed from 1973 to 2011 (n=9093)
      were obtained from the population-based Eindhoven cancer registry. Incidence time
      trends (European standardized rates per 100,000) were separately analyzed by sex,
      age group (<60, 60-74, and >75 years), subsite, and pathological stage. Joinpoint
      analyses were performed to discern trend breaks, age-period-cohort analyses to
      examine the influence of longitudinal and cross-sectional changes. RESULTS: The
      incidence of non-cardia cancer declined annually by 3.5% (95% CI -3.8; -3.3).
      However, in males <60 years, the incidence flattened since 2006, and tended to
      rise in those >74 years. This pertained to corpus cancers. The incidence of
      cardia cancer peaked in 1985 and decreased subsequently by 2.4% (95% CI -3.2; 
      1.5) yearly. The absolute incidence of stage IV disease at first diagnosis
      initially decreased, but then remained stable over the past 15-20 years.
      CONCLUSIONS: The incidence of non-cardia cancer declined over the past four
      decades in the Netherlands, but now seems to be stabilizing particularly in
      males. Unfavorable trend breaks are seen for corpus cancer in younger and older
      males. The trend breaks in the Netherlands are however not similar to those
      observed in the US.

PMID- 24309076
TI  - Antimicrobial and anti-biofilm effect of Bac8c on major bacteria associated with
      dental caries and Streptococcus mutans biofilms.
AB  - Dental caries is a common oral bacterial infectious disease. Its prevention and
      treatment requires control of the causative pathogens within dental plaque,
      especially Streptococcus mutans (S. mutans). Antimicrobial peptides (AMPs), one
      of the promising substitutes for conventional antibiotics, have been widely
      tested and used for controlling bacterial infections. The present study focuses
      on evaluating the potential of the novel AMPs cyclic bactenecin and its
      derivatives against bacteria associated with dental caries. The results indicate
      that Bac8c displayed highest activity against the bacteria tested, whereas both
      cyclic and linear bactenecin had weak antimicrobial activity. The cytotoxicity
      assay showed that Bac8c did not cause detectable toxicity at concentrations of 32
      128MUg/ml for 5min or 32-64MUg/ml for 60min. S. mutans and Lactobacillus fermenti
      treated with Bac8c showed variable effects on bacterial structure via scanning
      electron microscopy and transmission electron microscopy. There appeared to be a
      large amount of extracellular debris and obvious holes on the cell surface, as
      well as loss of cell wall and nucleoid condensation. The BioFlux system was
      employed to generate S. mutans biofilms under a controlled flow, which more
      closely resemble the formation process of natural biofilms. Bac8c remarkably
      reduced the viability of cells in biofilms formed in the BioFlux system. This
      phenomenon was further analyzed and verified by real-time PCR results of a
      significant suppression of the genes involved in S. mutans biofilm formation.
      Taken together, this study suggests that Bac8c has a potential clinical
      application in preventing and treating dental caries. 

PMID- 24309077
TI  - FDA official: "clinical trial system is broken".

PMID- 24309078
TI  - Scientists want G8 countries to quadruple funding for dementia research within 10
      years.

PMID- 24309079
TI  - Obama vows to persevere with healthcare changes.

PMID- 24309080
TI  - Residents' "handoff bundle" halved error rate, shows study.

PMID- 24309081
TI  - Split in commissioning between local authorities and health bodies is reducing
      access to sexual health services.

PMID- 24309082
TI  - Cardiac device infections is associated with pocket hematoma and diabetes
      mellitus: the role of the cardiovascular nurse.

PMID- 24309083
TI  - Initial experience with the balloon expandable Edwards-SAPIEN Transcatheter Heart
      Valve in Australia and New Zealand: the SOURCE ANZ registry: outcomes at 30 days
      and one year.
AB  - BACKGROUND: We report the findings of the SOURCE-ANZ registry of the clinical
      outcomes of the Edwards SAPIENTM Transcatheter Heart Valve (THV) in the
      Australian and New Zealand (ANZ) clinical environment. METHODS: This single arm
      registry of select patients treated in eight centres, represent the initial
      experience within ANZ with the balloon expandable Edwards SAPIEN THV delivered by
      transfemoral (TF) and transapical (TA) access. RESULTS: The total enrolment for
      the study was 132 patients, 63 patients treated by TF, 56 by TA, and 2 patients
      were withdrawn from the study. The mean ages: 83.7 (TF) and 81.7 (TA), female:
      34.3% (TF) and 61.3% (TA), logistic EuroSCORE: 26.8% (TF) and 28.8% (TA), and
      with procedural success (successful implant without conversion to surgery or
      death): 92.4% (TF) and 87.1% (TA) (p=0.32). Outcomes were not significantly
      different between TF and TA implants. These included one year mortality of 13.6%
      (TF) and 21.7% (TA) (p=0.24), MACCE: 16.7% (TF) and 28.3% (TA) (p=0.12),
      pacemaker: 4.6% (TF) and 8.3% (TA) (p=0.39), and VARC major vascular complication
      of 4.6% (TF) and 5.0% (TA) (p=0.91). CONCLUSION: TAVI in the ANZ clinical
      environment has demonstrated excellent outcomes for both the TA and TF approaches
      in highly selected patients. These results are consistent with those demonstrated
      in European, Canadian registries and the pivotal US clinical trials.
      ACTRN12611001026910.

PMID- 24309085
TI  - A randomized controlled trial evaluating a parenting program designed
      specifically for grandparents.
AB  - Grandparents providing regular child care to grandchildren contribute to the
      nurturing environment in which children are raised. This study evaluated the
      efficacy of a behavioral family intervention designed specifically for
      grandparents, Grandparent Triple P. Fifty-four grandparents (M = 60.89) and 48
      parents (M = 34.52) participated in the evaluation. Grandparents predominantly
      provided between 12 and 20 h of care per week (64.81%), to a grandchild (62%
      male) aged between 2 and 9 years (M = 4.42). Families were randomly assigned to
      one of two conditions (intervention or grandparent care-as-usual) and were
      assessed using a multiple informant approach at three time points
      (preintervention, postintervention, and six-month follow-up). Relative to the
      grandparent care-as-usual group, significant short-term improvements were found
      in the intervention group on grandparent-reported child behavior problems;
      parenting confidence; grandparent depression, anxiety, stress; and improved
      relationship with the parent. Parents also reported significant reductions in
      child behavior problems, despite not participating in the program. Short-term
      effects were predominantly maintained at six-month follow-up. 

PMID- 24309084
TI  - Use of mTOR inhibitors in chronic heart transplant recipients with renal failure:
      calcineurin-inhibitors conversion or minimization?
AB  - BACKGROUND: In the last decade, mTOR inhibitors (mTOR-is) have become the
      cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the
      preservation of post-transplant renal function. We compared utility and safety of
      the total replacement of calcineurin inhibitors with a mTOR-i with a strategy
      based on calcineurin inhibitor minimization and concomitant use of m-TOR-i.
      METHODS: In a retrospective multi-center cohort of 394 maintenance cardiac
      recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients
      in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159
      patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis
      was carried out to balance between group differences. RESULTS: Overall, after a
      median time of 2 years from mTOR-i initiation, between group differences for the
      evolution of renal function were not observed. In a multivariate adjusted model,
      improvement of renal function was limited to patients with mTOR-i usage within
      5years after transplantation, particularly with the conversion strategy, and in
      those patients who could maintain mTOR-i therapy. Significant differences between
      strategies were not found for mortality, infection and mTOR-i withdrawal due to
      drug-related adverse events. However, conversion group tended to have a higher
      acute rejection incidence than the minimization group (p=0.07). CONCLUSION: In
      terms of renal benefits, our results support an earlier use of mTOR-is,
      irrespective of the strategy. The selection of either a conversion or a CNI
      minimization protocol should be based on the clinical characteristics of the
      patients, particularly their rejection risk.

PMID- 24309086
TI  - Enhancing the anaerobic digestion potential of dairy waste activated sludge by
      two step sono-alkalization pretreatment.
AB  - High efficiency resource recovery from dairy waste activated sludge (WAS) has
      been a focus of attention. An investigation into the influence of two step sono
      alkalization pretreatment (using different alkaline agents, pH and sonic reaction
      times) on sludge reduction potential in a semi-continuous anaerobic reactor was
      performed for the first time in literature. Firstly, effect of sludge
      pretreatment was evaluated by COD solubilization, suspended solids reduction and
      biogas production. At optimized condition (4172 kJ/kg TS of supplied energy for
      NaOH - pH 10), COD solubilization, suspended solids reduction and biogas
      production was 59%, 46% and 80% higher than control. In order to clearly describe
      the hydrolysis of waste activated sludge during sono-alkalization pretreatment by
      a two step process, concentrations of ribonucleic acid (RNA) and bound
      extracellular polymeric substance (EPS) were also measured. Secondly, semi
      continuous process performance was studied in a lab-scale semi-continuous
      anaerobic reactor (5L), with 4 L working volume. With three operated SRTs, the
      SRT of 15 d was found to be most appropriate for economic operation of the
      reactor. Combining pretreatment with anaerobic digestion led to 58% and 62% of
      suspended solids and volatile solids reduction, respectively, with an improvement
      of 83% in biogas production. Thus, two step sono-alkalization pretreatment laid
      the basis in enhancing the anaerobic digestion potential of dairy WAS.

PMID- 24309087
TI  - Multibubble sonoluminescence as a tool to study the mechanism of formic acid
      sonolysis.
AB  - Sonoluminescence spectra collected from 0.1 to 3.0M aqueous solutions of formic
      acid sparged with argon show the OH(A(2)Sigma(+)-X(2)Pii) and C2(d(3)Pig ->
      a(3)Piu) emission bands and a broad continuum typical for multibubble
      sonoluminescence. The overall intensity of sonoluminescence and the sonochemical
      yield of HCOOH degradation vary in opposite directions: the sonoluminescence is
      quenched while the sonochemical yield increases with HCOOH concentration. By
      contrast, the concentration of formic acid has a relatively small effect on the
      intensity of C2 Swan band. It is concluded that C2 emission originates from CO
      produced by HCOOH degradation rather than from direct sonochemical degradation of
      HCOOH. The intensity of C2 band is much stronger at high ultrasonic frequency
      compared to 20 kHz ultrasound which is in line with higher yields of CO at high
      frequency. Another product of HCOOH sonolysis, carbon dioxide, strongly quenches
      sonoluminescence, most probably via collisional non-radiative mechanism.

PMID- 24309088
TI  - Cannabidiol as a potential treatment for psychosis.
AB  - Although cannabis use is associated with an increased risk of developing
      psychosis, the cannabis constituent cannabidiol (CBD) may have antipsychotic
      properties. This review concisely describes the role of the endocannabinoid
      system in the development of psychosis and provides an overview of currently
      available animal, human experimental, imaging, epidemiological and clinical
      studies that investigated the antipsychotic properties of CBD. In this targeted
      literature review we performed a search for English articles using Medline and
      EMBASE. Studies were selected if they described experiments with psychosis
      models, psychotic symptoms or psychotic disorders as outcome measure and involved
      the use of CBD as intervention. Evidence from several research domains suggests
      that CBD shows potential for antipsychotic treatment. 

PMID- 24309089
TI  - Two-photon polymerization of sub-micrometric patterned surfaces: investigation of
      cell-substrate interactions and improved differentiation of neuron-like cells.
AB  - Direct Laser Writing (DLW) is an innovative tool that allows the photofabrication
      of high resolution 3D structures, which can be successfully exploited for the
      study of the physical interactions between cells and substrates. In this work, we
      focused our attention on the topographical effects of submicrometric patterned
      surfaces fabricated via DLW on neuronal cell behavior. In particular, we
      designed, prepared, and characterized substrates based on aligned ridges for the
      promotion of axonal outgrowth and guidance. We demonstrated that both rat PC12
      neuron-like cells and human SH-SY5Y derived neurons differentiate on parallel 2.5
      MUm spaced submicrometric ridges, being characterized by strongly aligned and
      significantly longer neurites with respect to those differentiated on flat
      control substrates, or on more spaced (5 and 10 MUm) ridges. Furthermore, we
      detected an increased molecular differentiation toward neurons of the SH-SY5Y
      cells when grown on the submicrometric patterned substrates. Finally, we observed
      that the axons can exert forces able of bending the ridges, and we indirectly
      estimated the order of magnitude of these forces thanks to scanning probe
      techniques. Collectively, we showed as submicrometric structures fabricated by
      DLW can be used as a useful tool for the study of the axon mechanobiology. 

PMID- 24309090
TI  - Food security and cardiovascular disease risk among adults in the United States:
      findings from the National Health and Nutrition Examination Survey, 2003-2008.
AB  - INTRODUCTION: Little is known about the relationship between food security status
      and predicted 10-year cardiovascular disease risk. The objective of this study
      was to examine the associations between food security status and cardiovascular
      disease risk factors and predicted 10-year risk in a national sample of US
      adults. METHODS: A cross-sectional analysis using data from 10,455 adults aged 20
      years or older from the National Health and Nutrition Examination Survey 2003
      2008 was conducted. Four levels of food security status were defined by using 10
      questions. RESULTS: Among all participants, 83.9% had full food security, 6.7%
      had marginal food security, 5.8% had low food security, and 3.6% had very low
      food security. After adjustment, mean hemoglobin A1c was 0.15% greater and mean
      concentration of C-reactive protein was 0.8 mg/L greater among participants with
      very low food security than among those with full food security. The adjusted
      mean concentration of cotinine among participants with very low food security was
      almost double that of participants with full food security (112.8 vs 62.0 ng/mL,
      P < .001). No significant associations between food security status and systolic
      blood pressure or concentrations of total cholesterol, high-density lipoprotein
      cholesterol, or non-high-density lipoprotein cholesterol were observed.
      Participants aged 30 to 59 years with very low food security were more likely to
      have a predicted 10-year cardiovascular disease risk greater than 20% than fully
      food secure participants (adjusted prevalence ratio, 2.38; 95% CI, 1.31-4.31).
      CONCLUSION: Adults aged 30 to 59 years with very low food security showed
      evidence of increased predicted 10-year cardiovascular disease risk.

PMID- 24309091
TI  - Associations between county and municipality zoning ordinances and access to
      fruit and vegetable outlets in rural North Carolina, 2012.
AB  - INTRODUCTION: Zoning ordinances and land-use plans may influence the community
      food environment by determining placement and access to food outlets, which
      subsequently support or hinder residents' attempts to eat healthfully. The
      objective of this study was to examine associations between healthful food zoning
      scores as derived from information on local zoning ordinances, county
      demographics, and residents' access to fruit and vegetable outlets in rural
      northeastern North Carolina. METHODS: From November 2012 through March 2013,
      county and municipality zoning ordinances were identified and double-coded by
      using the Bridging the Gap food code/policy audit form. A healthful food zoning
      score was derived by assigning points for the allowed use of fruit and vegetable
      outlets. Pearson coefficients were calculated to examine correlations between the
      healthful food zoning score, county demographics, and the number of fruit and
      vegetable outlets. In March and April 2013, qualitative interviews were conducted
      among county and municipal staff members knowledgeable about local zoning and
      planning to ascertain implementation and enforcement of zoning to support fruit
      and vegetable outlets. RESULTS: We found a strong positive correlation between
      healthful food zoning scores and the number of fruit and vegetable outlets in 13
      northeastern North Carolina counties (r = 0.66, P = .01). Major themes in
      implementation and enforcement of zoning to support fruit and vegetable outlets
      included strict enforcement versus lack of enforcement of zoning regulations.
      CONCLUSION: Increasing the range of permitted uses in zoning districts to include
      fruit and vegetable outlets may increase access to healthful fruit and vegetable
      outlets in rural communities.

PMID- 24309092
TI  - Changes in children's oral health status and receipt of preventive dental visits,
      United States, 2003-2011/2012.
AB  - INTRODUCTION: Oral health represents the largest unmet health care need for
      children, and geographic variations in children's receipt of oral health services
      have been noted. However, children's oral health outcomes have not been
      systematically evaluated over time and across states. This study examined changes
      in parent-reported children's oral health status and receipt of preventive dental
      visits in 50 states and the District of Columbia. METHODS: We used data from the
      2003 and the 2011/2012 National Survey of Children's Health. National and state
      level estimates of the adjusted prevalence of oral health status and preventive
      dental visits were calculated and changes over time examined. Multivariable
      logistic regression was used to compare outcomes across all states and the
      District of Columbia for each survey year. RESULTS: The percentage of parents who
      reported that their children had excellent or very good oral health increased
      from 67.7% in 2003 to 71.9% in 2011/2012. Parents who reported that their
      children had preventive dental visits increased from 71.5% in 2003 to 77.0% in
      2011/2012. The prevalence of children with excellent or very good oral health
      status increased in 26 states, and the prevalence of children who received at
      least 1 preventive care dental visit increased in 45 states. In both years, there
      was more variation among states for preventive dental visits than for oral health
      status. CONCLUSIONS: State variation in oral health status and receipt of
      preventive dental services remained after adjusting for demographic
      characteristics. Understanding these differences is critical to addressing the
      most common chronic disease of childhood and achieving the oral health objectives
      of Healthy People 2020.

PMID- 24309093
TI  - Childhood adversity and adult onset of hypertension and heart disease in Sao
      Paulo, Brazil.
AB  - Using data from the Sao Paulo Megacity Mental Health Survey and logistic
      regression models, we studied how childhood neglect, physical abuse, sexual
      abuse, and family violence were related to adult hypertension and heart disease.
      After adjustment for sociodemographic factors, child physical abuse was
      associated with hypertension and heart disease, whereas family violence was
      associated with hypertension. Efforts to curb child physical abuse could
      potentially reduce subsequent hypertension and heart disease. 

PMID- 24309094
TI  - Pseudomonas aeruginosa biofilm: potential therapeutic targets.
AB  - Pseudomonas aeruginosa is a gram-negative pathogen that has become an important
      cause of infection, especially in patients with compromised host defense
      mechanisms. It is frequently related to nosocomial infections such as pneumonia,
      urinary tract infections (UTIs) and bacteremia. The biofilm formed by the
      bacteria allows it to adhere to any surface, living or non-living and thus
      Pseudomonal infections can involve any part of the body. Further, the adaptive
      and genetic changes of the micro-organisms within the biofilm make them resistant
      to all known antimicrobial agents making the Pseudomonal infections complicated
      and life threatening. Pel, Psl and Alg operons present in P. aeruginosa are
      responsible for the biosynthesis of extracellular polysaccharide which plays an
      important role in cell-cell and cell-surface interactions during biofilm
      formation. Understanding the bacterial virulence which depends on a large number
      of cell-associated and extracellular factors is essential to know the potential
      drug targets for future studies. Current novel methods like small molecule based
      inhibitors, phytochemicals, bacteriophage therapy, photodynamic therapy,
      antimicrobial peptides, monoclonal antibodies and nanoparticles to curtail the
      biofilm formed by P. aeruginosa are being discussed in this review. 

PMID- 24309095
TI  - Optimization of virus detection in cells using massively parallel sequencing.
AB  - Massively parallel sequencing (MPS)-based virus detection has potential
      regulatory applications. We studied the ability of one of these approaches, based
      on degenerate oligonucleotide primer (DOP)-polymerase chain reaction (PCR), to
      detect viral sequences in cell lines known to express viral genes or particles.
      DOP-PCR was highly sensitive for the detection of small quantities of isolated
      viral sequences. Detected viral sequences included nodavirus, bracovirus, and
      endogenous retroviruses in High Five cells, porcine circovirus type 1 and porcine
      endogenous retrovirus in PK15 cells, human T-cell leukemia virus 1 in MJ cells,
      human papillomavirus 18 in HeLa cells, human herpesvirus 8 in BCBL-1 cells, and
      Epstein-Barr Virus in Raji cells. Illumina sequencing (for which primers were
      most efficiently added using PCR) provided greater sensitivity for virus
      detection than Roche 454 sequencing. Analyzing nucleic acids extracted both
      directly from samples and from capsid-enriched preparations provided useful
      information. Although there are limitations of these methods, these results
      indicate significant promise for the combination of nonspecific PCR and MPS in
      identifying contaminants in clinical and biological samples, including cell lines
      and reagents used to produce vaccines and therapeutic products. 

PMID- 24309096
TI  - Repeated aripiprazole treatment regulates Bdnf, Arc and Npas4 expression under
      basal condition as well as after an acute swim stress in the rat brain.
AB  - Despite the rapid control of schizophrenic symptoms is due to the ability of
      antipsychotic drugs (APDs) to block D2 receptors in the mesolimbic pathway, it is
      now well-established that the therapeutic effects rely on adaptive mechanisms set
      in motion by their long-term administration. Such neuroplastic mechanisms depend
      on the pharmacological profile of the drug employed, with marked differences
      existing between first and second generation APDs. On these bases, the major
      accomplishment of this work was to investigate neuroadaptive changes set in
      motion by repeated treatment with aripiprazole, a novel APD that is unique for
      being a partial agonist at dopamine D2 receptors. Moreover, given that stress
      plays a critical role in the exacerbation of disease symptoms, we also
      investigated whether aripiprazole could influence the dynamic response of the
      brain to an acute challenge. We found that repeated aripiprazole treatment in
      rats regulates the expression of different markers of neuroplasticity such as
      Bdnf, Arc and Npas4 in a brain-region specific fashion; more importantly, the
      expression of these molecules was significantly up-regulated by an acute swim
      stress only in aripiprazole-treated animals, which is suggestive of increased
      ability to cope with the adverse event. We indeed found an overall facilitation
      of Bdnf expression, an effect that is mainly evident in the prefrontal cortex on
      the pool of transcripts undergoing dendritic localization. Overall, our results
      provide novel information regarding the mechanisms through which aripiprazole may
      regulate brain function and could contribute to improve neuroplastic defects that
      are associated with schizophrenia symptomatology. 

PMID- 24309097
TI  - Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer
      recognition and signaling of D2-5-HT2A heteroreceptor complexes.
AB  - Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells
      after cotransfection of the two receptors and shown to have bidirectional
      receptor-receptor interactions. In the current study the existence of D2L-5-HT2A
      heteroreceptor complexes was demonstrated also in discrete regions of the ventral
      and dorsal striatum with in situ proximity ligation assays (PLA). The
      hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist
      TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H
      raclopride binding sites and significantly reduced the pKiH values of the high
      affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments.
      Similar results were obtained in HEK293 cells and in ventral striatum. The
      effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were
      blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE
      luciferase reporter gene assay using cotransfected but not D2R singly transfected
      HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist
      quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the
      effects of both quinpirole alone and the enhancing actions of DOI and LSD while
      ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for
      the allosteric enhancement of the D2R protomer recognition and signalling
      observed is likely mediated by a biased agonist action of the hallucinogenic 5
      HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism
      may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A
      heteroreceptor complex may thus be a target for the psychotic actions of
      hallunicogenic 5-HT2A agonists. 

PMID- 24309098
TI  - Cell surface expression of MR1B, a splice variant of the MHC class I-related
      molecule MR1, revealed with antibodies.
AB  - The major histocompatibility complex (MHC) class I-related molecule, MR1, is
      highly conserved in mammals and can present bacteria-derived vitamin B
      metabolites to mucosal-associated invariant T (MAIT) cells, possibly having
      important defense function in the microbial infection. MR1B is a splice variant
      of MR1 and possesses an intriguing domain structure with only two extracellular
      domains resembling some NKG2D ligand molecules. Thus far, cell surface expression
      of MR1B could not be analyzed with flow cytometry due to a lack of appropriate
      antibodies reactive with MR1B. Here we clarified the expression of MR1B
      recombinant protein on the cell surface of the transfected cells by flow
      cytometry analyses using the antiserum against MR1. Consistently, MR1B tagged
      with FLAG peptide at the N-terminus also could be detected with anti-FLAG
      monoclonal antibodies. Our result showed that MR1B can be recognized on the cell
      surface by macromolecules such as antibodies, indicating its potential of
      interaction with certain receptor(s). We discuss possibility of interaction of
      MR1B and/or the full-length MR1 with some receptor(s) other than alphabeta T cell
      receptor (TCR) of MAIT cells based on the highly conserved characteristic
      residues of the ligand-binding domains of MR1 and its MAIT cells alphabetaTCR
      footprints. 

PMID- 24309099
TI  - Scd1 mammary-specific vector constructed and overexpressed in goat fibroblast
      cells resulting in an increase of palmitoleic acid and oleic acid.
AB  - Stearoyl-CoA desaturase-1 (Scd1) is a rate-limiting enzyme in the biosynthesis of
      monounsaturated fatty acids. Overexpression of Scd1 in transgenic animals would
      modify the nutritional value of ruminant-derived foods by increasing the
      monounsaturated fatty acid (MUFA) and decreasing the saturated fatty acid (SFA)
      content. The aim of this study was to develop an effective Scd1 vector that is
      specifically expressed in dairy goat mammary glands. We successfully amplified
      the goat full length Scd1 cDNA and evaluated its activity in goat ear skin
      derived fibroblast cells (GEFCs) by lipid analysis. In addition, we constructed a
      mammary gland-specific expression vector and confirmed efficient expression of
      Scd1 in goat mammary epithelial cells (GMECs) by qRT-PCR and Western blot
      analysis. Fatty acid analysis showed that Scd1-overexpression resulted in an
      increase in levels of palmitoleic acid (16:1n-7) and oleic acid (18:1n-9), from
      1.73 +/- 0.02% to 2.54 +/- 0.02% and from 27.25 +/- 0.13% to 30.37 +/- 0.04%,
      respectively (both p<0.01) and the ratio of MUFA to SFA was increased. This work
      lays a foundation for the generation of Scd1 transgenic goats.

PMID- 24309100
TI  - Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and
      mTORC2 inhibitor AZD-2014.
AB  - Colorectal cancer is a major contributor of cancer-related mortality. The
      mammalian target or rapamycin (mTOR) signaling is frequently hyper-activated in
      colorectal cancers, promoting cancer progression and chemo-resistance. In the
      current study, we investigated the anti-colorectal cancer effect of a novel mTOR
      complex 1 (mTORC1) and mTORC2 dual inhibitor: AZD-2014. In cultured colorectal
      cancer cell lines, AZD-2014 significantly inhibited cancer cell growth without
      inducing significant cell apoptosis. AZD-2014 blocked activation of both mTORC1
      (S6K and S6 phosphorylation) and mTORC2 (Akt Ser 473 phosphorylation), and
      activated autophagy in colorectal cancer cells. Meanwhile, autophagy inhibition
      by 3-methyaldenine (3-MA) and hydroxychloroquine, as well as by siRNA knocking
      down of Beclin-1 or ATG-7, inhibited AZD-2014-induced cytotoxicity, while the
      apoptosis inhibitor had no rescue effect. In vivo, AZD-2014 oral administration
      significantly inhibited the growth of HT-29 cell xenograft in SCID mice, and the
      mice survival was dramatically improved. At the same time, in xenografted tumors
      administrated with AZD-2014, the activation of mTORC1 and mTORC2 were largely
      inhibited, and autophagic markers were significantly increased. Thus, AZD-2014
      inhibits colorectal cancer cell growth both in vivo and in vitro. Our results
      suggest that AZD-2014 may be further investigated for colorectal cancer therapy
      in clinical trials. 

PMID- 24309101
TI  - Immunomodulatory effect of poly-gamma-glutamic acid derived from Bacillus
      subtilis on natural killer dendritic cells.
AB  - Bacillus subtilis-derived poly-gamma-glutamic acid (gammaPGA) stimulates
      dendritic cells (DCs) to produce IL12, leading to CD4(+) T cell differentiation
      toward the Th1 phenotype, but DCs consist of heterogeneous subpopulations with a
      variety of immune functions. Among these, natural killer dendritic cells (NKDCs)
      play an important role in anti-tumor immune responses. Herein, we demonstrate the
      role of NKDCs in gammaPGA-meditated anti-tumor immune responses. NK1.1(+)
      CD11c(+) NKDCs were stimulated upon gammaPGA stimulation in vitro and in vivo to
      up-regulate lymphocyte activation markers, MHC class I and II, and co-stimulatory
      molecules. In particular, NKDCs were activated by gammaPGA to produce IFNgamma
      and TNFalpha, like NK cells, as well as IL12, like DCs, implying that NKDCs have
      unique and multifunctional roles. Importantly, NKDCs stimulated by gammaPGA
      conferred stronger anti-tumor effects in mice and showed increased cytotoxicity
      against various tumor cell lines in vitro. In conclusion, NKDCs are one of the
      key players in anti-tumor immunity induced by gammaPGA. 

PMID- 24309102
TI  - supraHex: an R/Bioconductor package for tabular omics data analysis using a supra
      hexagonal map.
AB  - Biologists are increasingly confronted with the challenge of quickly
      understanding genome-wide biological data, which usually involve a large number
      of genomic coordinates (e.g. genes) but a much smaller number of samples. To meet
      the need for data of this shape, we present an open-source package called
      'supraHex' for training, analysing and visualising omics data. This package
      devises a supra-hexagonal map to self-organise the input data, offers scalable
      functionalities for post-analysing the map, and more importantly, allows for
      overlaying additional data for multilayer omics data comparisons. Via applying to
      DNA replication timing data of mouse embryogenesis, we demonstrate that supraHex
      is capable of simultaneously carrying out gene clustering and sample correlation,
      providing intuitive visualisation at each step of the analysis. By overlaying CpG
      and expression data onto the trained replication-timing map, we also show that
      supraHex is able to intuitively capture an inherent relationship between late
      replication, low CpG density promoters and low expression levels. As part of the
      Bioconductor project, supraHex makes accessible to a wide community in a simple
      way, what would otherwise be a complex framework for the ultrafast understanding
      of any tabular omics data, both scientifically and artistically. This package can
      run on Windows, Mac and Linux, and is freely available together with many
      tutorials on featuring real examples at http://supfam.org/supraHex. 

PMID- 24309103
TI  - EpCAM expression in the prostate cancer makes the difference in the response to
      growth factors.
AB  - INTRODUCTION: Epithelial cell adhesion molecule (EpCAM) is expressed in tumors
      with an epithelial cell of origin, in a heterogeneous manner. Prostate cancer
      stem-like cells highly express EpCAM. However, little is known about how EpCAM is
      involved in the ability of cells to adapt to micro-environmental changes in
      available growth factors, which is one of the essential biological phenotypes of
      cancer stem-like cells (CSCs). METHODS: EpCAM-high and EpCAM-low subpopulations
      of cells were established from the prostate cancer cell line PC-3. Signal
      transductions in response to serum starvation, and on the exposure to EGF ligand
      or the specific inhibitor were analyzed in terms. Furthermore, we analyzed the
      expression level of amino acid transporters which contribute to the activation of
      mTOR signal between the two subgroups. RESULTS: EpCAM-high and EpCAM-low PC-3
      subpopulations showed markedly different responses to serum starvation. EpCAM
      expression was positively correlated with activation of the mTOR and epithelial
      growth factor receptor (EGFR) signaling pathways. Furthermore, AMP-activated
      protein kinase (AMPK) was gradually de-activated in EpCAM-low PC-3 cells in the
      absence of serum. CONCLUSIONS: EpCAM regulates the AMPK signaling pathway,
      essential for the response to growth factors characterized by EGF. LAT1, the
      amino acid transporter stabilized at the cellular membrane by EpCAM, is likely to
      be responsible for the difference in the susceptibility to EGF between EpCAM-high
      and EpCAM-low PC-3 cells.

PMID- 24309104
TI  - The effects of miR-467b on lipoprotein lipase (LPL) expression, pro-inflammatory
      cytokine, lipid levels and atherosclerotic lesions in apolipoprotein E knockout
      mice.
AB  - Atherosclerosis is a lipid disorder disease characterized by chronic blood vessel
      wall inflammation driven by the subendothelial accumulation of macrophages.
      Studies have shown that lipoprotein lipase (LPL) participates in lipid
      metabolism, but it is not yet known whether post-transcriptional regulation of
      LPL gene expression by microRNAs (miRNAs) occurs in vivo. Here, we tested that
      miR-467b provides protection against atherosclerosis by regulating the target
      gene LPL which leads to reductions in LPL expression, lipid accumulation,
      progression of atherosclerosis and production of inflammatory cytokines in
      apolipoprotein E knockout (apoE(-/-)) mice. Treatment of apoE(-/-) mice with
      intra-peritoneal injection of miR-467b agomir led to decreased blood plasma
      levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein
      cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta and monocyte chemotactic
      protein-1 (MCP-1). Using Western blots and real time PCR, we determined that LPL
      expression in aorta and abdominal cavity macrophages were significantly down
      regulated in the miR-467b agomir group. Furthermore, systemic treatment with miR
      467b antagomir accelerated the progression of atherosclerosis in the aorta of
      apoE(-/-) mice. The present study showed that miR-467b protects apoE(-/-) mice
      from atherosclerosis by reducing lipid accumulation and inflammatory cytokine
      secretion via downregulation of LPL expression. Therefore, targeting miR-467b may
      offer a promising strategy to treat atherosclerotic vascular disease. 

PMID- 24309105
TI  - Design and expression of a short peptide as an HIV detection probe.
AB  - To explore a low-cost novel probe for HIV detection, we designed and prepared a
      50-amino acid-length short fusion peptide (FP-50) via Escherichia coli in vivo
      expression. It was employed as a novel probe to detect HIV-1 gp120 protein. The
      detectable level of gp120 protein using the FP-50 peptide was approximately 20
      200 times lower than previously published methods that used a pair of monoclonal
      antibodies. Thus, this short peptide is a very promising component for detection
      of gp120 protein during early stages of HIV infection. 

PMID- 24309106
TI  - Identification of a novel Ser/Thr protein phosphatase Ppq1 as a negative
      regulator of mating MAP kinase pathway in Saccharomyces cerevisiae.
AB  - The specificity and efficiency of cell signaling is largely governed by the
      complex formation of signaling proteins. The precise spatio-temporal control of
      the complex assembly is crucial for proper signaling and cell survival. Protein
      phosphorylation is a key mechanism of signal processing in most of cell signaling
      networks. Phosphatases, along with kinases, control the phosphorylation state of
      many proteins and thus play a critical role in the precise regulation of
      signaling at each stage such as activation, propagation, and adaptation.
      Identification and functional analysis of pathway-specific phosphatase is,
      therefore, crucial for the understanding of cell signaling mechanisms. Here, we
      have developed a novel screening strategy to identify pathway-specific
      phosphatases, in which the entire repertoire of cell's phosphatases was tethered
      to a signaling complex and the changes in signaling response were monitored. As a
      model target, we have chosen the mating MAP kinase pathway in the budding yeast,
      which is composed of three kinases and Ste5 scaffold protein. Using this
      strategy, a putative Ser/Thr phosphatase, Ppq1, was identified to be mating
      specific. Results show that Ppq1 down-regulates mating signaling by targeting at
      or upstream of the terminal MAP kinase Fus3 in the cascade. The catalytic
      activity of Ppq1 as a phosphatase was confirmed in vitro and is necessary for its
      function in the regulation of mating signaling. Overall, the data suggest that
      Ppq1 functions as a negative regulator of mating MAPK pathway by
      dephosphorylating target pathway protein(s) and plays a key role in the control
      of the background signaling noise. 

PMID- 24309107
TI  - Expression analysis of histone acetyltransferases in rice under drought stress.
AB  - Histone acetylation is one of the vital reversible modifications of chromatin
      structure that regulates gene expression in eukaryotes. Histone
      acetyltransferases (HATs) and histone deacetylases (HDACs) maintain the
      homeostasis of histone acetylation. Studies in Arabidopsis have revealed that
      HATs are involved in plant responses to various stresses including light,
      temperature, salt and ABA. Drought stress, a very common environmental stress,
      could cause a range of physiological and biochemical responses in plants
      involving HATs. Eight HATs in four different families (CBP, GNAT, MYST, and
      TAF(II)250 family) are known in rice. In this research, four OsHATs, one from
      each family, were chosen based on in silico domain and promoter analysis for
      their response under drought conditions. Drought stress was introduced to two
      leaf-stage rice seedlings. The effectiveness of drought treatment was confirmed
      by the measurement of relative water content (RWC). Real-time quantitative
      polymerase chain reaction analysis demonstrated that drought stress caused a
      significant increase in the expression of four HATs (OsHAC703, OsHAG703, OsHAF701
      and OsHAM701) in rice plants. Additionally, the Western-blot analysis showed that
      the acetylation level on certain lysine sites of H3 (lysine 9, lysine 18 and
      lysine 27) and H4 (lysine 5) increased with OsHATs expression. The significant
      increase in the transcript levels of OsHATs and the acetylation level of lysine
      residues on Histone H3 and H4 suggest that OsHATs are involved in drought stress
      responses in rice.

PMID- 24309108
TI  - Fibronectin alters the rate of formation and structure of the fibrin matrix.
AB  - Plasma fibronectin is a vital component of the fibrin clot; however its role on
      clot structure is not clearly understood. The goal of this study was to examine
      the influence of fibronectin on the kinetics of formation, structural
      characteristics and composition of reconstituted fibrin clots or fibrin matrices.
      Fibrin matrices were formed by adding thrombin to 1, 2 or 4 mg/ml fibrinogen
      supplemented with 0-0.4 mg/ml fibronectin. The rate of fibrin matrix formation
      was then monitored by measuring light absorbance properties at different time
      points. Confocal microscopy of fluorescein conjugated fibrinogen was used to
      visualize the structural characteristics of fibrin matrices. The amount of
      fibronectin in fibrin matrices was determined through electrophoresis and
      immunoblotting of solubilized matrices. Fibronectin concentration positively
      correlated with the initial rate of fibrin matrix formation and with steady state
      light absorbance values of fibrin matrices. An increase in fibronectin
      concentration resulted in thinner and denser fibers in the fibrin matrices.
      Electrophoresis and immunoblotting showed that fibronectin was covalently and non
      covalently bound to fibrin matrices and in the form of high molecular weight
      multimers. The formation of fibronectin multimers was attributed to cross-linking
      of fibronectin by trace amounts Factor XIIIa. These findings are novel because
      they link results from light absorbance studies to microcopy analyses and
      demonstrate an influence of fibronectin on fibrin matrix structural
      characteristics. This data is important in developing therapies that destabilize
      fibrin clots.

PMID- 24309109
TI  - Molecular identification of aiiA homologous gene from endophytic Enterobacter
      species and in silico analysis of putative tertiary structure of AHL-lactonase.
AB  - The aiiA homologous gene known to encode AHL- lactonase enzyme which hydrolyze
      the N-acylhomoserine lactone (AHL) quorum sensing signaling molecules produced by
      Gram negative bacteria. In this study, the degradation of AHL molecules was
      determined by cell-free lysate of endophytic Enterobacter species. The percentage
      of quorum quenching was confirmed and quantified by HPLC method (p<0.0001).
      Amplification and sequence BLAST analysis showed the presence of aiiA homologous
      gene in endophytic Enterobacter asburiae VT65, Enterobacter aerogenes VT66 and
      Enterobacter ludwigii VT70 strains. Sequence alignment analysis revealed the
      presence of two zinc binding sites, "HXHXDH" motif as well as tyrosine residue at
      the position 194. Based on known template available at Swiss-Model, putative
      tertiary structure of AHL-lactonase was constructed. The result showed that novel
      endophytic strains of Enterobacter genera encode the novel aiiA homologous gene
      and its structural importance for future study. 

PMID- 24309110
TI  - Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin
      deficiency and elevated expression of slow-type muscle fiber genes.
AB  - Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal
      region of the Pnn protein sequence is highly conserved from mammals to insects,
      but the C-terminal RS domain-containing region is absent in lower species. The N
      terminal coiled-coil domain (CCD) is, therefore, of interest not only from a
      functional point of view, but also from an evolutionarily standpoint. To explore
      the biological role of the Pnn CCD in a physiological context, we generated
      transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that
      overexpression of the CCD reduces endogenous Pnn expression in cultured cell
      lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited
      reduced body mass and impaired muscle function during development. Mutant
      skeletal muscles show dystrophic histological features with muscle fibers heavily
      loaded with centrally located myonuclei. Expression profiling and pathway
      analysis identified over-representation of genes in gene categories associated
      with muscle contraction, specifically those related to slow type fiber. In
      addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal
      muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular
      dystrophic phenotype associated with NEB deficiency and the CCD domain is
      incapable of replacing full length Pnn in terms of functional capacity. 

PMID- 24309111
TI  - Human C-kit+CD45- cardiac stem cells are heterogeneous and display both cardiac
      and endothelial commitment by single-cell qPCR analysis.
AB  - C-kit expressing cardiac stem cells have been described as multipotent. We have
      previously identified human cardiac C-kit+CD45- cells, but only found evidence of
      endothelial commitment. A small cardiac committed subpopulation within the C
      kit+CD45- population might however be present. To investigate this at single-cell
      level, right and left atrial biopsies were dissociated and analyzed by FACS. Only
      right atrial biopsies contained a clearly distinguishable C-kit+CD45- population,
      which was single-cell sorted for qPCR. A minor portion of the sorted cells (1.1%)
      expressed early cardiac gene NKX2.5 while most of the cells (81%) expressed late
      endothelial gene VWF. VWF- cells were analyzed for a wider panel of genes. One
      group of these cells expressed endothelial genes (FLK-1, CD31) while another
      group expressed late cardiac genes (TNNT2, ACTC1). In conclusion, human C
      kit+CD45- cells were predominantly localized to the right atrium. While most of
      these cells expressed endothelial genes, a minor portion expressed cardiac genes.

PMID- 24309112
TI  - Perillyl alcohol suppresses antigen-induced immune responses in the lung.
AB  - Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and
      geranylgeranyl transferase, key enzymes that induce conformational and functional
      changes in small G proteins to conduct signal production for cell proliferation.
      Thus, it has been tried for the treatment of cancers. However, although it
      affects the proliferation of immunocytes, its influence on immune responses has
      been examined in only a few studies. Notably, its effect on antigen-induced
      immune responses has not been studied. In this study, we examined whether POH
      suppresses Ag-induced immune responses with a mouse model of allergic airway
      inflammation. POH treatment of sensitized mice suppressed proliferation and
      cytokine production in Ag-stimulated spleen cells or CD4(+) T cells. Further,
      sensitized mice received aerosolized OVA to induce allergic airway inflammation,
      and some mice received POH treatment. POH significantly suppressed indicators of
      allergic airway inflammation such as airway eosinophilia. Cytokine production in
      thoracic lymph nodes was also significantly suppressed. These results demonstrate
      that POH suppresses antigen-induced immune responses in the lung. Considering
      that it exists naturally, POH could be a novel preventive or therapeutic option
      for immunologic lung disorders such as asthma with minimal side effects. 

PMID- 24309113
TI  - Nucleoprotein of influenza B virus binds to its type A counterpart and disrupts
      influenza A viral polymerase complex formation.
AB  - Upon co-infection with influenza B virus (FluB), influenza A virus (FluA)
      replication is substantially impaired. Previously, we have shown that the
      nucleoprotein of FluB (BNP) can inhibit FluA polymerase machinery, retarding the
      growth of FluA. However, the molecular mechanism underlying this inhibitory
      action awaited further investigation. Here, we provide evidence that BNP hinders
      the proper formation of FluA polymerase complex by competitively binding to the
      nucleoprotein of FluA. To exert this inhibitory effect, BNP must be localized in
      the nucleus. The interaction does not require the presence of the viral RNA but
      needs an intact BNP RNA-binding motif. The results highlight the novel role of
      BNP as an anti-influenza A viral agent and provide insights into the mechanism of
      intertypic interference. 

PMID- 24309115
TI  - Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein
      (NuMA).
AB  - Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1)
      plays a critical role in a variety of cellular functions including cell cycle
      control, replication, and transcriptional regulation. Nuclear mitotic apparatus
      protein (NuMA) localizes to spindle poles during mitosis, and is an essential
      component in the formation and maintenance of mitotic spindle poles. Here we show
      that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine
      1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation.
      Interestingly, SUMO modification of endogenous NuMA occurs at the entry into
      mitosis and this modification is reversed after exiting from mitosis. Knockdown
      of Ubc9 or forced expression of SENP1 results in impairment of the localization
      of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA
      mutant is defective in microtubule bundling, and multiple spindles are induced
      during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might
      contribute to NuMA-mediated formation and maintenance of mitotic spindle poles
      during mitosis. 

PMID- 24309114
TI  - Bovine alpha-2-HS-glycoprotein functions as a booster antigen for efficiently
      stimulating humoral immune responses to CCR5 and SIVmac239 envelope glycoprotein.
AB  - The presence of anti-CCR5 and anti-HIV-1 envelope glycoprotein (ENV) gp41
      antibodies (Abs) at sites of HIV-1 exposure was effective in preventing its
      transmission to HIV-1-exposed seronegative (ESN) subjects. Here, we design an
      immunogen that can induce Abs against CCR5 and SIVmac239 ENV simultaneously and
      show that bovine alpha-2-HS-glycoprotein (bAHSG) functions as a booster antigen
      for efficiently stimulating humoral immune responses to CCR5 and ENV. Initially,
      we generated a rhesus CCR5-derived cyclopeptide (cDDR5) conjugated with a
      recombinant trimeric SIVmac239 Env. When inguinally administered to rhesus
      macaques, the immunogen simultaneously induced both anti-CCR5 and anti-ENV Abs in
      sera, and the purified serum IgG fraction exerted an inhibitory effect on
      SIVmac239 infection in vitro. When further boosted with bAHSG, the responses of
      both Abs were significantly enhanced. To examine the cross-reactivity of bAHSG,
      it was administered to naive cynomolgus macaques. The results showed a
      statistically significant increase in IgG response against cynomolgus CCR5 and
      SIVmac239 ENV, and the induction of neutralizing activity against SIVmac239.
      These findings suggest that bAHSG is useful for immune strategies aimed at
      generating Abs against CCR5 and ENV simultaneously to confer HIV-protective
      immunity. 

PMID- 24309116
TI  - Understanding cross-communication between aboveground and belowground tissues via
      transcriptome analysis of a sucking insect whitefly-infested pepper plants.
AB  - Plants have developed defensive machinery to protect themselves against herbivore
      and pathogen attacks. We previously reported that aboveground whitefly (Bemisia
      tabaci Genn.) infestation elicited induced resistance in leaves and roots and
      influenced the modification of the rhizosphere microflora. In this study, to
      obtain molecular evidence supporting these plant fitness strategies against
      whitefly infestation, we performed a 300 K pepper microarray analysis using leaf
      and root tissues of pepper (Capsicum annuum L.) applied with whitefly, benzo
      (1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH), and the combination
      of BTH+whitefly. We defined differentially expressed genes (DEGs) as genes
      exhibiting more than 2-fold change (1.0 based on log2 values) in expression in
      leaves and roots in response to each treatment compared to the control. We
      identified a total of 16,188 DEGs in leaves and roots. Of these, 6685, 6752, and
      4045 DEGs from leaf tissue and 6768, 7705, and 7667 DEGs from root tissue were
      identified in the BTH, BTH+whitefly, and whitefly treatment groups, respectively.
      The total number of DEGs was approximately two-times higher in roots than in
      whitefly-infested leaves subjected to whitefly infestation. Among DEGs, whitefly
      feeding induced salicylic acid and jasmonic acid/ethylene-dependent signaling
      pathways in leaves and roots. Several transporters and auxin-responsive genes
      were upregulated in roots, which can explain why biomass increase is facilitated.
      Using transcriptome analysis, our study provides new insights into the molecular
      basis of whitefly-mediated intercommunication between aboveground and belowground
      plant tissues and provides molecular evidence that may explain the alteration of
      rhizosphere microflora and root biomass by whitefly infestation.

PMID- 24309117
TI  - Radiologic case study. Acrometastasis of the thumb.

PMID- 24309118
TI  - Caring for the incarcerated: an orthopedic perspective.
AB  - According to the 1976 Supreme Court case of Estelle v Gamble, the government is
      required to provide prisoners access to the necessary care for known, serious
      medical needs. Failure to do so violates the Eighth Amendment prohibiting the
      imposition of "cruel and unusual punishment." Currently, more than 2.5 million
      Americans are imprisoned, the highest per capita rate in the world. In the
      current fiscal climate and with burgeoning health care costs for society as a
      whole, providing care for prisoners poses both moral and logistical challenges.
      From an orthopedic standpoint, caring for the incarcerated raises uniquely
      challenging issues due to the nature of this patient population and their types
      of musculoskeletal conditions.

PMID- 24309119
TI  - Dupuytren's contracture.

PMID- 24309120
TI  - Osteoporotic ankle fractures: an approach to operative management.
AB  - The incidence of osteoporosis is increasing as the elderly population grows.
      Because these patients remain active, fragility fractures of the ankle are
      becoming more common. The literature indicates a relatively high complication
      rate for non-operative management of ankle fractures in this patient cohort,
      leading surgeons to face challenges unique to patients with poor bone and skin
      quality. This article discusses techniques to address osteoporotic ankle
      fractures and reviews the current literature relevant to this issue.

PMID- 24309121
TI  - Management of instability and osteolysis after total hip arthroplasty.

PMID- 24309122
TI  - Metrics and textural features of MRI diffusion to improve classification of
      pediatric posterior fossa tumors.
AB  - BACKGROUND AND PURPOSE: Qualitative radiologic MR imaging review affords limited
      differentiation among types of pediatric posterior fossa brain tumors and cannot
      detect histologic or molecular subtypes, which could help to stratify treatment.
      This study aimed to improve current posterior fossa discrimination of histologic
      tumor type by using support vector machine classifiers on quantitative MR imaging
      features. MATERIALS AND METHODS: This retrospective study included preoperative
      MRI in 40 children with posterior fossa tumors (17 medulloblastomas, 16 pilocytic
      astrocytomas, and 7 ependymomas). Shape, histogram, and textural features were
      computed from contrast-enhanced T2WI and T1WI and diffusivity (ADC) maps.
      Combinations of features were used to train tumor-type-specific classifiers for
      medulloblastoma, pilocytic astrocytoma, and ependymoma types in separation and as
      a joint posterior fossa classifier. A tumor-subtype classifier was also produced
      for classic medulloblastoma. The performance of different classifiers was
      assessed and compared by using randomly selected subsets of training and test
      data. RESULTS: ADC histogram features (25th and 75th percentiles and skewness)
      yielded the best classification of tumor type (on average >95.8% of
      medulloblastomas, >96.9% of pilocytic astrocytomas, and >94.3% of ependymomas by
      using 8 training samples). The resulting joint posterior fossa classifier
      correctly assigned >91.4% of the posterior fossa tumors. For subtype
      classification, 89.4% of classic medulloblastomas were correctly classified on
      the basis of ADC texture features extracted from the Gray-Level Co-Occurence
      Matrix. CONCLUSIONS: Support vector machine-based classifiers using ADC histogram
      features yielded very good discrimination among pediatric posterior fossa tumor
      types, and ADC textural features show promise for further subtype discrimination.
      These findings suggest an added diagnostic value of quantitative feature analysis
      of diffusion MR imaging in pediatric neuro-oncology.

PMID- 24309124
TI  - Pretreatment advanced imaging in patients with stroke treated with IV
      thrombolysis: evaluation of a multihospital data base.
AB  - BACKGROUND AND PURPOSE: CT angiography, CT perfusion, and MR imaging have all
      been advocated as potentially useful in treatment planning for patients with
      acute ischemic stroke. We evaluated a large multihospital data base to determine
      how the use of advanced imaging is evolving in patients treated with intravenous
      thrombolysis. MATERIALS AND METHODS: Patients with acute ischemic stroke
      receiving IV thrombolytic therapy from 2008 to 2011 were identified by using the
      Premier Perspective data base. Mortality and discharge to long-term care rates
      were compared following multivariate logistic regression between patients who
      received head CT only versus those who received CTA without CT perfusion, CT
      perfusion, or MR imaging. RESULTS: Of 12,429 included patients, 7305 (59%) were
      in the CT group, 2359 (19%) were in the CTA group, 848 (7%) were in the CTP
      group, and 1917 (15%) were in the MR group. From 2008 to 2011, the percentage of
      patients receiving head CT only decreased from 64% to 55%, while the percentage
      who received cerebral CT perfusion increased from 3% to 8%. The use of CT
      angiography and MR imaging marginally increased (1%-2%). Outcomes were similar
      between CT only and advanced imaging patients, except discharge to long-term care
      was slightly more frequent in the CTP group (OR = 1.17 [95% CI, 0.96-1.43]; P =
      .0412) and MR group (OR = 1.14 [95% CI, 1.01-1.28]; P = .0177) and mortality was
      lower in the MR group (OR = 0.64 [95% CI, 0.52-0.79]; P < .0001). CONCLUSIONS:
      Use of advanced imaging is increasing in patients treated with IV thrombolysis.
      While there were differences in outcomes among imaging groups, the clinical
      effect of advanced imaging remains unclear.

PMID- 24309123
TI  - CT perfusion for detection of delayed cerebral ischemia in aneurysmal
      subarachnoid hemorrhage: a systematic review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Delayed cerebral ischemia is a significant cause of
      morbidity and mortality after aneurysmal SAH, leading to poor outcomes. The
      purpose of this study was to evaluate the usefulness of CTP in determining
      delayed cerebral ischemia in patients with aneurysmal SAH. MATERIALS AND METHODS:
      We conducted a systematic review evaluating studies that assessed CTP in patients
      with aneurysmal SAH for determining delayed cerebral ischemia. Studies using any
      of the following definitions of delayed cerebral ischemia were included in the
      systematic review: 1) new onset of clinical deterioration, 2) cerebral infarction
      identified on follow-up CT or MR imaging, and 3) functional disability. A random
      effects meta-analysis was performed assessing the strength of association between
      a positive CTP result and delayed cerebral ischemia. RESULTS: The systematic
      review identified 218 studies that met our screening criteria, of which 6 cohort
      studies met the inclusion criteria. These studies encompassed a total of 345
      patients, with 155 (45%) of 345 patients classified as having delayed cerebral
      ischemia and 190 (55%) of 345 patients as not having delayed cerebral ischemia.
      Admission disease severity was comparable across all groups. Four cohort studies
      reported CTP test characteristics amenable to the meta-analysis. The weighted
      averages and ranges of the pooled sensitivity and specificity of CTP in the
      determination of delayed cerebral ischemia were 0.84 (0.7-0.95) and 0.77 (0.66
      0.82), respectively. The pooled odds ratio of 23.14 (95% CI, 5.87-91.19)
      indicates that patients with aneurysmal SAH with positive CTP test results were
      approximately 23 times more likely to experience delayed cerebral ischemia
      compared with patients with negative CTP test results. CONCLUSIONS: Perfusion
      deficits on CTP are a significant finding in determining delayed cerebral
      ischemia in aneurysmal SAH. This may be helpful in identifying patients with
      delayed cerebral ischemia before development of infarction and neurologic
      deficits.

PMID- 24309125
TI  - Review of blood pressure control rates and outcomes.
AB  - Despite the high prevalence of hypertension and documented benefits of blood
      pressure (BP) control, >40% of patients with hypertension are not controlled. A
      majority of uncontrolled hypertensive patients receive two or more
      antihypertensive drugs. The current review examined the relationship between
      antihypertensive combination drug therapy, achievement of goal BP, and
      cardiovascular (CV) outcomes. Articles were selected from a PubMed search using a
      prespecified search strategy. Randomized, controlled clinical trials of adult
      human subjects published in English between January 1991 and January 2013 were
      included. From 2319 identified articles, 28 met inclusion criteria and contained
      a total of 226,877 subjects. There were seven placebo-controlled studies and 21
      treatment comparator and combination therapy studies. The studies included in
      this review reported a positive association between the degree of BP lowering,
      number of medications, and CV outcomes. As combination therapy became available,
      it was increasingly utilized in clinical trials and enabled an increased
      proportion of patients to achieve a prespecified BP target. Adverse events with
      monotherapy and combination therapy were as anticipated for the specific classes
      of antihypertensive therapy. Although many patients reach BP goal, combination
      antihypertensive therapy is often needed to reach BP goal. Effective BP lowering
      has been shown to result in improvements in CV outcomes. 

PMID- 24309126
TI  - Hyperplastic corneal pannus: an immunohistochemical analysis and review.
AB  - An exuberant corneal pannus usually develops in adults with a history of surgery
      or trauma in the anterior central stroma and appears as a glistening,
      vascularized, moderately elevated, well circumscribed white nodule. We describe a
      78-year-old woman with such a pannus, which in the past has typically been
      referred to as keloidal or hypertrophic. The involved eye had only light
      perception, and she underwent a penetrating keratoplasty that improved her vision
      to 20/100. Histopathologic and immunohistochemical evaluations of a the specimen
      disclosed a reactive spindle cell stromal proliferation of myofibroblasts that
      were smooth muscle actin positive with a low Ki67 proliferation index. Desmin,
      caldesmon, and calponin were negative, in keeping with the incomplete
      myofilamentary differentiation of a myofibroblast. There was a generous admixture
      of CD68/163-positive histiocytes and dispersed C3/5-positive T-lymphocytes. An
      absence of CD138- and IgG4-positive plasma cells ruled out an IgG4-related
      disease. For a lesion to be keloidal, the collagen must have a thick hyaline
      character, sharp edges, and a sparsity of intervening cells and vessels. A
      hypertrophic pannus would be composed of large swollen cells not necessarily
      increased in number. We therefore recommend adoption of the term hyperplastic for
      lesions like that described here because of the obvious increase in cellularity
      from proliferating myofibroblasts and the lack of true keloidal collagen. 

PMID- 24309127
TI  - Vision function abnormalities in Alzheimer disease.
AB  - Alzheimer disease (AD) is a progressive, age-related debilitating condition that
      is a growing public health problem in the developed world. Visual system
      abnormalities in AD were recognized in the early 1970s, but were initially
      considered to be of strictly cortical origin. Studies in the past 20 years reveal
      that all parts of the visual system may be affected, including the optic nerve
      and the retina. Some aspects of this involvement are still not well understood
      and are the subjects of intensive research. We summarize and focus on findings
      that may be of more practical interest to the ophthalmologist.

PMID- 24309128
TI  - Human intervertebral disc stiffness correlates better with the Otsu threshold
      computed from axial T2 map of its posterior annulus fibrosus than with clinical
      classifications.
AB  - Degeneration of the intervertebral disc, sometimes associated with low back pain
      and abnormal spinal motions, represents a major health issue with high costs. A
      non-invasive degeneration assessment via qualitative or quantitative MRI
      (magnetic resonance imaging) is possible, yet, no relation between mechanical
      properties and T2 maps of the intervertebral disc (IVD) has been considered,
      albeit T2 relaxation time values quantify the degree of degeneration. Therefore,
      MRI scans and mechanical tests were performed on 14 human lumbar intervertebral
      segments freed from posterior elements and all soft tissues excluding the IVD.
      Degeneration was evaluated in each specimen using morphological criteria,
      qualitative T2 weighted images and quantitative axial T2 map data and stiffness
      was calculated from the load-deflection curves of in vitro compression, torsion,
      lateral bending and flexion/extension tests. In addition to mean T2, the OTSU
      threshold of T2 (TOTSU), a robust and automatic histogram-based method that
      computes the optimal threshold maximizing the distinction of two classes of
      values, was calculated for anterior, posterior, left and right regions of each
      annulus fibrosus (AF). While mean T2 and degeneration schemes were not related to
      the IVDs' mechanical properties, TOTSU computed in the posterior AF correlated
      significantly with those classifications as well as with all stiffness values.
      TOTSU should therefore be included in future degeneration grading schemes. 

PMID- 24309129
TI  - Multiple-class antimicrobial resistance surveillance in swine Escherichia coli
      F4, Pasteurella multocida and Streptococcus suis isolates from Ontario and the
      impact of the 2004-2006 Porcine Circovirus type-2 Associated Disease outbreak.
AB  - The objective of this work was to describe trends in multiple-class antimicrobial
      resistance present in clinical isolates of Escherichia coli F4, Pasteurella
      multocida and Streptococcus suis from Ontario swine 1998-2010. Temporal changes
      in multiple-class resistance varied by the pathogens examined; significant yearly
      changes were apparent for the E. coli and P. multocida data. Although not present
      in the E. coli data, significant increases in multiple-class resistance within P.
      multocida isolates occurred from 2003 to 2005, coinciding with the expected
      increase in antimicrobials used to treat clinical signs of Porcine Circovirus
      Associated Disease (PCVAD) before it was confirmed. Prospective temporal scan
      statistics for multiple-class resistance suggest that significant clusters of
      increased resistance may have been found in the spring of 2004; months before the
      identification of the PCVAD outbreak in the fall of 2004. 

PMID- 24309130
TI  - Temporal patterns of human and canine Giardia infection in the United States:
      2003-2009.
AB  - Giardia protozoa have been suspected to be of zoonotic transmission, including
      transmission from companion animals such as pet dogs to humans. Patterns of
      infection have been previously described for dogs and humans, but such
      investigations have used different time periods and locations for these two
      species. Our objective was to describe and compare the overall trend and
      seasonality of Giardia species infection among dogs and humans in the United
      States from 2003 through 2009 in an ecological study using public health
      surveillance data and medical records of pet dogs visiting a large nationwide
      private veterinary hospital. Canine data were obtained from all dogs visiting
      Banfield hospitals in the United States with fecal test results for Giardia
      species, from January 2003 through December 2009. Incidence data of human cases
      from the same time period were obtained from the CDC. Descriptive time plots, a
      seasonal trend decomposition (STL) procedure, and seasonal autoregressive moving
      average (SARIMA) models were used to assess the temporal characteristics of
      Giardia infection in the two species. Canine incidence showed a gradual decline
      from 2003 to 2009 with no significant/distinct regular seasonal component. By
      contrast, human incidence showed a stable annual rate with a significant regular
      seasonal cycle, peaking in August and September. Different temporal patterns in
      human and canine Giardia cases observed in this study suggest that the
      epidemiological disease processes underlying both series might be different, and
      Giardia transmission between humans and their companion dogs seems uncommon. 

PMID- 24309131
TI  - SnO2 nanoslab as NO2 sensor: identification of the NO2 sensing mechanism on a
      SnO2 surface.
AB  - Among the various metal oxides, SnO2 has been most widely exploited as a
      semiconductor gas sensor for its excellent functionalities. Models illustrating
      the sensing mechanism of SnO2 have been proposed and tested to explain
      experimentally derived "power laws". The models, however, are often based on
      somewhat simplistic assumptions; for instance, the net charge transfer from an
      adsorbate to a sensor surface site is assumed to occur only by integer values
      independent of the crystallographic planes. In this work, we use layer-shaped
      SnO2 crystallites with one nanodimension (1ND-crystallites) as NO2 gas sensing
      elements under flat band conditions, and derive appropriate "power laws" by
      combining the dynamics of gas molecules on the sensor surface with a depletion
      theory of semiconductor. Our experimentally measured sensor response as a
      function of NO2 concentration when compared with the theoretically derived power
      law indicates that sensing occurs primarily through the chemisorption of single
      NO2 molecules at oxygen vacancy sites on the sensor surface. 

PMID- 24309132
TI  - beta-Glucuronidase and beta-glucosidase activity and human fecal water
      genotoxicity in the presence of probiotic lactobacilli and the heterocyclic
      aromatic amine IQ in vitro.
AB  - The aim of the study was to assess the genotoxicity of fecal water (FW) and the
      activity of fecal enzymes (beta-glucuronidase and beta-glucosidase) after
      incubation with 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) and probiotic
      lactobacilli: Lb. casei 0900, Lb. casei 0908, and Lb. paracasei 0919. Our results
      show that the carcinogen IQ greatly increased FW genotoxicity (up to 16.92 +/-
      3.03 U/mg) and the activity of fecal enzymes (up to even 1.4 +/- 0.16 U/mg) in 15
      individuals (children, adults and elderly). After incubation with IQ, the
      activity of beta-glucuronidase was reduced by Lactobacillus bacteria by 76.0%
      (Lb. paracasei 0908) in the FW of children, and by 82.0% (Lb. paracasei 0919) in
      the elderly; while that of beta-glucosidase was reduced by 55.0% in children (Lb.
      casei 0908) and 90.0% (Lb. paracasei 0919) in elderly subjects. Lactobacilli
      decreased the genotoxicity of FW after incubation with IQ to the greatest extent
      in adults (by 64.5%). Probiotic lactobacilli, in the presence of IQ, efficiently
      inhibits activity of fecal enzymes to the level of control. Genotoxicity
      inhibition depends on the person's age, its individual microbiota and diet.

PMID- 24309133
TI  - Diallyl trisulfide-induced apoptosis of bladder cancer cells is caspase-dependent
      and regulated by PI3K/Akt and JNK pathways.
AB  - Diallyl trisulfide (DATS) is one of the major organosulfur components of garlic
      (Allium sativum L.), which inhibits the proliferation of various cancer cells,
      but the exact mechanisms of this action in human bladder cancer cells still
      remain largely unresolved. In this study, we investigated how DATS induces
      apoptosis in T24 human bladder cancer cells in vitro. Treatment of T24 cells with
      DATS resulted in potent anti-proliferative activity. Additionally, some typical
      apoptotic characteristics, such as chromatin condensation and an increase in the
      population of sub-G1 hypodiploid cells, were observed. With respect to the
      mechanism underlying the induction of apoptosis, DATS reduced the expression of
      anti-apoptotic Bcl-2 and Bcl-xL, and inhibitor of apoptosis protein family
      proteins, but the expression of pro-apoptotic Bax and death receptor-related
      proteins was increased compared with the controls. DATS also activated caspase-8
      and -9, the respective initiator caspases of the extrinsic and the intrinsic
      apoptotic pathways. The increase in mitochondrial membrane depolarization was
      correlated with activation of effector caspase-3 and cleavage of poly-ADP-ribose
      polymerase, a vital substrate of activated caspase-3. Blockage of caspase
      activation through treatment with a pan-caspase inhibitor consistently inhibited
      apoptosis and abrogated growth inhibition in DATS-treated T24 cells. The study
      further investigated the roles of the phosphatidylinositol 3-kinase (PI3K)/Akt
      and mitogen-activated protein kinases (MAPKs) pathways with respect to the
      apoptotic effect of DATS, and showed that DATS deactivates Akt. Additionally,
      DATS activates extracellular signal-regulated kinase (ERK) and c-Jun N-terminal
      protein kinase (JNK), but not p38 MAPK, in T24 cells. Unlike ERK, JNK inhibitors
      reversed DATS-induced apoptosis and growth inhibition; however, inhibition of
      PI3K/Akt notably enhanced the apoptotic action of DATS. The results suggest that
      the pro-apoptotic activity of DATS is probably regulated by a caspase-dependent
      cascade through the activation of both intrinsic and extrinsic signaling
      pathways, which is mediated through the blocking of PI3K/Akt and the activation
      of the JNK pathway. 

PMID- 24309134
TI  - Unraveling the binding mechanism of polyoxyethylene sorbitan esters with bovine
      serum albumin: a novel theoretical model based on molecular dynamic simulations.
AB  - To gain a better understanding of the interactions governing the binding
      mechanism of proteins with non-ionic surfactants, the association processes of
      Tween 20 and Tween 80 with the bovine serum albumin (BSA) protein were
      investigated using molecular dynamics (MD) simulations. Protein:surfactant molar
      ratios were chosen according to the critical micelle concentration (CMC) of each
      surfactant in the presence of BSA. It was found that both the hydrophilic and the
      hydrophobic groups of the BSA equally contribute to the surface area of
      interaction with the non-ionic surfactants. A novel theoretical model for the
      interactions between BSA and these surfactants at the atomic level is proposed,
      where both surfactants bind to non-specific domains of the BSA three-dimensional
      structure mainly through their polyoxyethylene groups, by hydrogen bonds and van
      der Waals interactions. This is well supported by the strong electrostatic and
      van der Waals interaction energies obtained in the calculations involving
      surfactant polyoxyethylene groups and different protein regions. The results
      obtained from the MD simulations suggest that the formation of surfactant
      clusters over the BSA structure, due to further cooperative self-assembly of
      Tween molecules, could increase the protein conformational stability. These
      results extend the current knowledge on molecular interactions between globular
      proteins and non-ionic surfactants, and contribute to the fine-tuning design of
      protein formulations using polysorbates as excipients for minimizing the
      undesirable effects of protein adsorption and aggregation. 

PMID- 24309135
TI  - DNA adsorption onto calcium aluminate and silicate glass surfaces.
AB  - A common technique for small-scale isolation of genomic DNA is via adsorption of
      the DNA molecules onto a silica scaffold. In this work, the isolation capacities
      of calcium aluminate based glasses were compared against a commercially available
      silica scaffold. Silica scaffolds exhibit a negative surface at the physiological
      pH values used during DNA isolation (pH 5-9), while the calcium aluminate glass
      microspheres exhibit a positive surface charge. Isolation data demonstrates that
      the positively charged surface enhanced DNA adsorption over the negatively
      charged surface. DNA was eluted from the calcium aluminate surface by shifting
      the pH of the solution to above its IEP at pH 8. Iron additions to the calcium
      aluminate glass improved the chemical durability without compromising the surface
      charge. Morphology of the glass substrate was also found to affect DNA isolation;
      43-106 MUm diameter soda lime silicate microspheres adsorbed a greater quantity
      of genomic DNA than silica fibers with an average diameter of ~2 MUm.

PMID- 24309136
TI  - Plasma treatment of PDMS for applications of in vitro motility assays.
AB  - In vitro motility assays are readily used to simplify the complex environments
      within the cell and in muscle tissue. These assays have afforded considerable
      insight into the fundamentals of their underlying biophysics, interactions with
      cargo, intracellular regulation, and motor cooperation/competition. Extension of
      the standard in vitro motility assay into a more automated and cost-effective
      fluidic design while providing availability to the scientific community without
      expertise in lithographic fabrication is critical for the continued advancement
      of the field. In this work, we utilized a standard plasma cleaner to oxidize the
      widely prevalent material polydimethylsiloxane (PDMS) to create flow cells that
      could be used for in vitro motility assays. Our analysis indicated that a 40 min
      pre-treatment of the PDMS with plasma exposure resulted in optimal bundle
      motility. This finding was attributed to the condition at which the least amount
      of oxygen permeates the PDMS slab, enters the motility buffer, and oxidizes the
      motor proteins. Based on these findings, we developed a method for constructing
      microfluidic devices from glass and plasma-treated PDMS molds in which motility
      could be observed.

PMID- 24309137
TI  - Molecular cloning, characterization and expression analysis of three heat shock
      responsive genes from Haliotis diversicolor.
AB  - In this study, molecular characterization and expression of three heat shock
      responsive genes were analyzed as indicators to understand the mechanism of heat
      shock response of small abalone Haliotis diversicolor under stresses. The full
      length cDNA of heat shock transcriptional factor 1 (HdHSF1), heat shock factor
      binding protein 1(HSBP1), and heat shock protein 90 (HdHSP90) are 1548 bp, 809
      bp, and 2592 bp respectively, encoding a protein of 515 aa, 75 aa, and 728 aa
      respectively. Real time quantitative PCR analysis revealed that these three genes
      are constitutively expressed in 7 selected tissues. The expression level of
      HdHSF1 in gills was higher than that in other tissues (p < 0.05). The highest
      expression level of HdHSBP1 was detected in hemocytes. The highest expression
      level of HdHSP90 was in the digestive tract and colleterial gland. The HdHSF1
      expression level in the gills was up-regulated significantly (p < 0.05) after
      thermal stress and hypoxia exposure respectively. On the contrary, HdHSBP1 was
      down-regulated both in gills and hemocytes after thermal stress and the same as
      in gills after hypoxia stress. HdHSP90 expression level was also up-regulated in
      gills and hemocytes after both thermal and hypoxia stresses. These results
      indicated that these three heat shock responsive genes play important roles in
      response to thermal and hypoxia stress. 

PMID- 24309138
TI  - Acute aerocystitis in Nile tilapia bred in net cages and supplemented with
      chromium carbochelate and Saccharomyces cerevisiae.
AB  - Oreochromis niloticus bred in net cages were supplemented with cell wall of
      Saccharomyces cerevisiae (Sc) (0.3%) or chromium carbochelate (Cr) (18 mg/kg of
      feed) or in association (Sc + Cr), for 90 days. After this period, acute
      inflammation was induced in the swim bladder by inoculation of 3 * 10(8) CFU of
      inactivated Streptococcus agalactiae, and another group received 0.65% saline
      solution (control). Twelve, 24, and 48 h after stimulation, the inflammation was
      evaluated through total and differential counting of accumulated cells, and
      through leukocyte respiratory burst in the blood, cortisolemia, glycemia and
      serum lysozyme concentration. The results showed that there were greater total
      numbers of cells in the exudate of fish inoculated with inactivated bacterium
      than in those injected with saline solution, with predominance of lymphocytes,
      thrombocytes, macrophages and granulocytes. Tilapia supplemented with Cr
      presented increased total numbers of cells with significant accumulation of
      lymphocytes and reductions in cortisolemia and glycemia, but the different
      treatments did not have any influence on leukocyte respiratory burst or serum
      lysozyme concentration. Tilapia supplemented with Sc and the Cr + Sc association
      did not present significant changes to the variables evaluated, despite higher
      accumulation of lymphocytes in the inflammatory exudate from fish treated with
      Sc. The results indicate that tilapia bred in net cages and supplemented with Cr
      presented higher total accumulation of cells at the inflammatory focus, thus
      indicating an increase in the inflammatory response induced by the bacterium,
      probably due to the reduction in cortisolemia and higher glucose consumption.
      Thus, supplementation with Cr had beneficial action, which facilitated
      development of acute inflammation induced by the bacterium, but did not affect
      neither leukocyte respiratory burst in the blood nor serum lysozyme
      concentration.

PMID- 24309139
TI  - Brain dynamics of attention and working memory engagement in subitizing.
AB  - This study addressed the engagement of attention and working memory, as inferred
      from electrophysiological measurements, in the processing of small sets of
      objects. We recorded N2pc and CDA, two lateralized components of the EEG signal
      associated respectively with individuation and visual working memory, while
      participants enumerated a variable number (1-9) of uniquely colored targets among
      distractors. Behavioral results showed a clear subitizing effect, with lower
      error rates for smaller (1-3 targets) than larger sets. ERP results showed that
      both N2pc and CDA amplitudes increased as a function of target numerosity up to
      approximately three targets. However, individual differences in the enumeration
      efficiency were correlated only with the individual variation in the N2pc
      modulations. The results suggest that the constraints of the attentional
      individuation system play a significant role in the occurrence of the subitizing
      phenomenon. 

PMID- 24309140
TI  - Cilostazol inhibits leukocyte-endothelial cell interactions in murine
      microvessels after transient bilateral common carotid artery occlusion.
AB  - Leukocyte behavior in the cerebral microvasculature following vessel occlusion
      has not been fully elucidated. The purpose of this study was to investigate the
      effects of cilostazol on leukocyte behavior (rolling and adhesion) in murine
      cerebral microvessels following transient bilateral carotid artery occlusion
      using intravital fluorescence microscopy. Four groups of mice were assigned: a
      sham group (n=16); an ischemia (induced by 15-min occlusion of bilateral common
      carotid arteries) and reperfusion (I/R) group (n=13); I/R+cilostazol (I/R+CZ3
      mg/kg) group (I/R after oral administration of cilostazol at 3 mg/kg) (n=8); and
      I/R+cilostazol (I/R+CZ30 mg/kg) group (I/R after oral administration of
      cilostazol at 30 mg/kg) (n=12). Leukocytes labeled with 0.05% acridine orange
      were administered intravenously and their behavior was investigated at 3 and 6 h
      after reperfusion. Numbers of rolling or adherent leukocytes were expressed as
      the count per square millimeter per 30s. Numbers of rolling and adherent
      leukocytes at 3 and 6h after reperfusion were significantly higher in the I/R
      group than in the sham or I/R+CZ30 mg/kg groups in both pial veins (P<0.05) and
      pial arteries (P<0.05). Cilostazol (30 mg/kg) inhibited leukocyte-endothelial
      interactions following cerebral ischemia and reperfusion.

PMID- 24309141
TI  - Differential involvement of two cortical masticatory areas in submandibular
      salivary secretion in rats.
AB  - To evaluate the role of the masticatory area in the cerebral cortex in the
      masticatory-salivary reflex, we investigated submandibular salivary secretion,
      jaw-movement trajectory and electromyographic activity of the jaw-opener
      (digastric) and jaw-closer (masseter) muscles evoked by repetitive electrical
      stimulation of the cortical masticatory area in anesthetized rats. Rats have two
      cortical masticatory areas: the anterior area (A-area) in the orofacial motor
      cortex, and the posterior area (P-area) in the insular cortex. Our defined P-area
      extended more caudally than the previous reported one. P-area stimulation induced
      vigorous salivary secretion (about 20 ul/min) and rhythmical jaw movements (3-4
      Hz) resembling masticatory movements. Salivary flow persisted even after
      minimizing jaw movements by curarization. A-area stimulation induced small and
      fast rhythmical jaw movements (6-8 Hz) resembling licking of solutions, but not
      salivary secretion. These findings suggest that P-area controls salivary
      secretion as well as mastication, and may be involved in the masticatory-salivary
      reflex.

PMID- 24309142
TI  - Chronic diseases and individual risk for workplace injury.

PMID- 24309143
TI  - Protective effect of total flavonoids extracted from the leaves of Murraya
      paniculata (L.) Jack on diabetic nephropathy in rats.
AB  - This study was designed to evaluate the effects of total flavonoids extracted
      from the leaves of Murraya paniculata (L.) Jack (TFMP) on diabetic nephropathy.
      High fat diet and streptozotocin-induced diabetic rats were treated with the TFMP
      (35 or 70 mg/kg) for 13 weeks. Changes of renal function parameters were examined
      at the end of administration. Some kidneys were collected for histological and
      immunohistochemistry studies, the other ones for biochemical parameters analysis.
      TFMP significantly decreased the levels of serum blood urea nitrogen, serum
      creatinine, creatinine clearance, interleukin-6, urinary albumin, 24h-urinary
      albumin excretion rate, kidney weight to body weight ratio and fasting blood
      glucose in diabetic rats. Meanwhile, the levels of triglycerides, total and LDL
      cholesterols in the TFMP treated diabetic rats were lower and the high-density
      lipoprotein cholesterol level was higher than that in the diabetic rats. TFMP
      treatment significantly blocked the decrease of superoxide dismutase and
      glutathione peroxidase and increase of malondialdehyde levels in diabetic rats.
      Furthermore, the TFMP not only decreased the expression of TGF-beta1 and CTGF
      protein, but also reduced diabetes-induced morphological alterations of the
      kidney. These results suggest that TFMP is a protective agent against renal
      damage in diabetic nephropathy.

PMID- 24309144
TI  - A two-generation reproduction study with transgenic Bt rice TT51 in Wistar rats.
AB  - TT51 is a transgenic Bt rice created by fusion a synthetic CryAb/CryAc gene into
      rice MingHui63. A significant number of animal feeding studies with transgenic
      crops have been carried out with the rapid development of transgenic crops.
      However, the evidence is far from identifying whether certain novel transgenic
      crops possess potential danger for human or animal health after long-term
      consumption. Rice-based diets, containing 60% ordinary grocery rice, MingHui63
      rice or TT51 rice by weight, were fed to two generations of male and female rats
      in order to determine the potential reproductive effects of TT51. In this study,
      both clinical performance variables and histopathological responses were examined
      and compared between groups. There were no significant differences between groups
      on body weights, food consumption, reproductive data and relative organ/body
      weights. There were some statistically significant differences in hematology and
      serum chemistry parameters, but no histological abnormalities were seen in the
      brain, heart, liver, spleen, kidneys, stomach, small intestine, thymus, ovaries,
      uterus, testes and epididymides. Based on the results, under the circumstance of
      this study TT51 show no significant differences on reproduction performance of
      rats compared with MingHui63 and the control. 

PMID- 24309145
TI  - In vitro genotoxicity assessment of MTES, GPTES and TEOS, three precursors
      intended for use in food contact coatings.
AB  - Organoalkoxysilanes are precursors that are used increasingly in the synthesis of
      food contact coatings. To comply with the EU regulation, their potential toxicity
      must be assessed, and very little information is known. The genotoxicity of three
      common precursors was studied, namely, tetraethylorthosilicate (TEOS),
      methyltriethoxysilane (MTES) and 3-glycidyloxypropyltriethoxysilane (GPTES). By
      the Ames test, MTES and TEOS were not mutagenic for bacteria. A significant
      positive response was observed with GPTES in the TA100 and TA1535 strains. The
      mutagenic effect was more pronounced in the presence of the exogenous metabolic
      activation system with an increase of the induction factor (ten-fold higher for
      the TA1535 strain). In the micronucleus assay performed with a human hepatoma
      cell line (HepG2 cells), GPTES gave negative results even in the presence of an
      exogenous activation system. To ascertain the possibility of using this precursor
      in food contact material, its migration must be monitored according to the
      coating formulation because migration might result in hazardous human exposure. 

PMID- 24309146
TI  - Discovery of soluble epoxide hydrolase inhibitors from natural products.
AB  - With the goal of developing soluble epoxide hydrolase (sEH) inhibitors with novel
      chemical structures, the sEH inhibitory activities of 30 natural compounds were
      evaluated using both a fluorescent substrate, 3-phenyl-cyano(6-methoxy-2
      naphthalenyl)methyl ester- 2-oxiraneacetic acid, and a physiological substrate,
      14,15-epoxyeicosatrienoic acid. To evaluate the selectivity of sEH inhibition,
      the inhibition of microsomal epoxide hydrolase (mEH), which plays a critical role
      in detoxification of toxic epoxides, was determined using human liver microsomes.
      Honokiol and beta-amyrin acetate, isolated from Magnolia officinalis and Acer
      mandshuricum, respectively, displayed strong inhibition of sEH activity, with
      respective IC50 values of 0.57 MUM and 3.4 MUM determined using the fluorescent
      substrate, and 1.7 MUM and 6.1 MUM determined using 14,15-epoxyeicosatrienoic
      acid. mEH activity was decreased to 49% or 61% of control activity by 25 MUM
      honokiol or beta-amyrin acetate, respectively. These results suggest that beta
      amyrin acetate and honokiol exhibit sEH inhibitory activity, although their sEH
      selectivity should be improved.

PMID- 24309148
TI  - The JFFMA assessment of flavoring substances structurally related to menthol and
      uniquely used in Japan.
AB  - Using the procedure devised by the Joint FAO/WHO Expert Committee on Food
      Additives (JECFA), we performed safety evaluations on four flavoring substances
      structurally related to menthol (L-menthyl 2-methylbutyrate, DL-menthyl
      octanoate, DL-menthyl palmitate, and DL-menthyl stearate) uniquely used in Japan.
      While no genotoxicity study data were available in the literature, all four
      substances had no chemical structural alerts predictive of genotoxicity.
      Moreover, they all four are esters consisting of menthol and simple carboxylic
      acids that were assumed to be immediately hydrolyzed after ingestion and
      metabolized into innocuous substances for excretion. As menthol and carboxylic
      acids have no known genotoxicity, it was judged that the JECFA procedure could be
      applied to these four substances. According to Cramer's classification, these
      substances were categorized as class I based on their chemical structures. The
      estimated daily intakes for all four substances were within the range of 1.54
      4.71 MUg/person/day and 60-1250 MUg/person/day, using the methods of Maximized
      Survey-Derived Intake and Single Portion Exposure Technique, respectively, based
      on the annual usage data of 2001, 2005, and 2010 in Japan. As the daily intakes
      of these substances were below the threshold of concern applied to class I
      substances viz., 1800 MUg/person/day, it was concluded that all four substances
      raise no safety concerns when used for flavoring foods under the currently
      estimated intake levels.

PMID- 24309147
TI  - Evaluation of N-acetyl-cysteine against tetrachlorobenzoquinone-induced
      genotoxicity and oxidative stress in HepG2 cells.
AB  - Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol
      (PCP). Although the genotoxic effect of PCP has been comprehensively
      investigated, there is little known about TCBQ's genotoxic effects. In the
      current study, TCBQ was tested for its genotoxicity using HepG2 cells as
      experimental model. To select the exposure concentration of interest, cell
      viability was measured and three concentrations were used for further
      investigation. In single cell gel electrophoresis (SCGE) assay, concentration
      dependent increase in tail length, tail DNA percentage and tail moment were
      detected following TCBQ exposure. Micronucleus (MN) assay indicated TCBQ
      gradually increased MN frequency and decreased nuclear division index (NDI).
      Enzyme-linked immunosorbent assay (ELISA) and western blotting analyses both
      showed TCBQ caused histone H2AX phosphorylation (gamma-H2AX). Furthermore, the
      elevation of 8-hydroxydeoxyguanosine (8-OHdG) and reactive oxygen species (ROS)
      level indicated TCBQ-induced genotoxicity is associated with oxidative stress. On
      the other hand, N-acetyl-cysteine (NAC) administration significantly protected
      cells from the genotoxic effect of TCBQ. Overall, our data suggested TCBQ exerted
      genotoxic effect possibly via an oxidative damage mechanism in HepG2 cells and
      this toxicity is prevented by pretreatment with NAC. 

PMID- 24309149
TI  - Microsurgical clipping of intracranial aneurysms assisted by green indocyanine
      videoangiography (ICGV) and ultrasonic perivascular microflow probe measurement.
AB  - OBJECTIVES: The purpose of this work is to assess the surgical and clinical
      outcome of intracranial aneurysm clipping performed combining the assistance of
      green indocyanine videoangiography (ICGV) and ultrasonic perivascular microflow
      probe. PATIENTS AND METHODS: Data from patients affected with intracranial
      aneurysms who underwent microsurgical clipping assisted by both techniques
      between May 2012 and April 2013 were retrospectively evaluated. RESULTS: 26
      patients with 34 aneurysms (25 unruptured) were enrolled. In a total of 11
      aneurysms (32%), the vascular clip needed repositioning, since either the post
      clipping microprobe assessment detected a significant flow reduction of the
      explored vessels (8 cases, 23%) or ICGV identified a residual non-obliterated
      aneurysm (3 cases, 9%). A second clip repositioning was required in 3 cases (9%)
      because of dome remnant showed with ICGV. In all cases, final microprobe and ICGV
      assessments showed a complete exclusion of the aneurysm, without evidence of
      vascular flow impairment. Postoperatively, 1 patient (3%) presented a residual
      neck aneurysm. No permanent morbidity was reported. CONCLUSION: With the limits
      of our small case series, our results testify that the presented approach may
      provide high exclusion rate in the treatment of cerebral aneurysm with very low
      morbidity in selected patients.

PMID- 24309150
TI  - Stroke associated with pituitary apoplexy in a giant prolactinoma: a case report.

PMID- 24309151
TI  - Correlation of diffusion tensor, dynamic susceptibility contrast MRI and (99m)Tc
      Tetrofosmin brain SPECT with tumour grade and Ki-67 immunohistochemistry in
      glioma.
AB  - OBJECTIVE: Assessment of the grade and type of glioma is of paramount importance
      for prognosis. Tumour proliferative potentials may provide additional information
      on the behaviour of the tumour, its response to treatment and prognosis. The
      purpose of this study was to investigate the correlation between diffusion tensor
      imaging (DTI), dynamic susceptibility contrast (DSC) magnetic resonance imaging
      (MRI) and (99m)Tc-Tetrofosmin brain single-photon emission computed tomography
      (SPECT), and the tumour grade and Ki-67 labelling index in newly diagnosed
      gliomas. METHODS: Study was made of patients with suspected glioma on brain MRI
      between December 2010 and January 2012, by DTI, DSC MRI and (99m)Tc-Tetrofosmin
      brain SPECT. The proliferative activity of each tumour was measured by deriving
      the Ki-67 proliferation index from immunohistochemical staining of tumour
      specimens. RESULTS: Glioma was newly diagnosed in 25 patients (17 men, 8 women,
      aged 19-79 years, median 55 years). The Ki-67 index ranged from 1% to 80% (mean
      19.4%). On evaluation of the relationship between the (99m)Tc-Tetrofosmin tumour
      uptake by gliomas was found to be significantly correlated with cellular
      proliferation (rho=0.924, p<0.0001). Regarding DTI, significant negative
      correlation was demonstrated between the apparent diffusion coefficient (ADC)
      ratio and the Ki-67 index (rho=-0.545, p=0.0087). Significant correlation was
      also observed between the fractional anisotropy (FA) ratio and the Ki-67 index
      (rho=0.489, p=0.02). Strong correlation was found between relative cerebral blood
      volume (rCBV) and Ki-67 index (rho=0.853, p<0.0001), and between the (99m)Tc
      Tetrofosmin lesion-to-normal (L/N) uptake ratio and rCBV (rho=0.808, p <=
      0.0001). Significant negative correlation was demonstrated between the (99m)Tc
      Tetrofosmin L/N ratio and ADC ratio (rho=-0.513, p=0.014). These imaging
      techniques were able to distinguish between low-grade and high-grade gliomas.
      CONCLUSIONS: Findings on DSC MRI and brain SPECT with (99m)Tc-Tetrofosmin metrics
      were more closely correlated with glioma cellular proliferation.

PMID- 24309152
TI  - Transcranial color-coded Doppler assessment of cerebral arteriovenous
      malformation hemodynamics in patients treated surgically or with staged
      embolization.
AB  - OBJECTIVE: The etiology of hemodynamic disturbances following embolization or
      surgical resection of arteriovenous malformations (AVMs) has not been fully
      explained. The aim of the study was the assessment of the selected hemodynamic
      parameters in patients treated for cerebral AVMs using transcranial color-coded
      Doppler sonography (TCCS). MATERIALS AND METHODS: Forty-six adult patients (28
      males, 18 females, aged 41 +/- 13 years, mean +/- SD) diagnosed with AVMs who
      were consecutively admitted to the Department of Neurosurgery between 2000 and
      2012 treated surgically or with staged embolization were enrolled in the study.
      All patients were examined with TCCS assessing mean flow velocity (Vm), the
      pulsatility index (PI) and vasomotor reactivity (VMR) in all main intracranial
      arteries. The examined parameters were assessed in the vessel groups (feeding,
      ipsilateral and contralateral to the AVM) and they were compared between the
      examinations, i.e. at admission, within 24h after the first embolization or
      surgical resection (I control), and before the second embolization (II control).
      RESULTS: In feeders which were completely obliterated or surgically resected--I
      control examination showed a nonsignificant Vm decrease. The difference between
      Vm before embolization and II control examination was significant (102.0 +/- 47.8
      cm/s vs 54.3 +/- 19.4 cm/s, p<0.01). A significant increase in PI (0.72 +/- 0.18
      vs 0.94 +/- 0.24, p<0.01) and VMR (1.80 +/- 0.59 vs 2.78 +/- 0.78, p<0.01) of
      feeding vessels was observed in I control. No further increase in PI or in VMR
      was observed. In embolized feeding vessels after partial AVM embolization I
      control examination showed a significant decrease in Vm (116.1 +/- 32.6 cm/s vs
      93.4 +/- 33.0 cm/s, p<0.01). No further significant decrease in Vm was noted. The
      pulsatility index increased significantly (I control, 0.54 +/- 0.11 vs 0.66 +/-
      0.15, p<0.01) and then decreased nonsignificantly (II control). No statistically
      significant differences were found in VMR values between pretreatment, I and II
      control examinations. Both Vm in the ipsilateral internal carotid artery and the
      ratio of Vm of the embolized vessel to Vm of the corresponding contralateral
      vessel were significantly higher in I control examination compared to II control
      examination (111.8 +/- 44.0 cm/s vs 101.3 +/- 40.6 cm/s, p<0.01; 1.63 +/- 0.61 vs
      1.37 +/- 0.62, p<0.01; respectively). No statistically significant correlation
      was observed between the decrease in Vm or the increase in PI in the embolized
      vessels and the reduction of AVM volume. In the nonembolized feeding vessels
      after partial AVM embolization II control examination revealed the increase in Vm
      and a significant decrease in PI (0.71 +/- 0.21 vs 0.62 +/- 0.16, p<0.01)
      compared to I examination. No statistically significant changes in the VMR value
      in the nonembolized feeders between the pretreatment, I and II control
      examinations were noted. CONCLUSIONS: The decrease in Vm and the increase in the
      PI in the embolized feeding vessels after the first complete embolization or
      surgical resection is observed, whereas the PI returned to normal values before
      Vm does. The observed decrease in Vm and an increase in the PI in embolized AVM
      feeders after complete or partial embolization do not correlate with the extent
      of embolization. In these vessels a relative increase in blood flow velocity is
      maintained within the first 24h following embolization as compared to
      contralateral vessels. The increase in Vm is not related to disturbances in VMR.
      Blood redistribution to the nonembolized AVM feeders is observed after partial
      AVM embolization.

PMID- 24309153
TI  - FMRI of deep brain stimulation at the rat ventral posteromedial thalamus.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) of deep brain
      stimulation (DBS) has potentials to reveal neuroanatomical connectivity of a
      specific brain region in vivo. OBJECTIVE: This study aimed to demonstrate
      frequency and amplitude tunings of the thalamocortical tract using DBS fMRI at
      the rat ventral posteromedial thalamus. METHODS: Blood oxygenation level
      dependent (BOLD) fMRI data were acquired in a total of twelve rats at a high
      field 11.7 T MRI scanner with modulation of nine stimulus frequencies (1-40 Hz)
      and seven stimulus amplitudes (0.2-3.6 mA). RESULTS: BOLD response in the barrel
      cortex peaked at 25 Hz. The response increased with stimulus amplitude and
      reached a plateau at 1 mA. Cortical spreading depolarization (CSD) was observed
      occasionally after DBS that carries >10% BOLD waves spanning the entire
      ipsilateral cortex. CONCLUSION: fMRI is sensitive to the frequency effect of DBS
      and has potential to investigate the function of a particular neuroanatomical
      pathway.

PMID- 24309154
TI  - Inhibition of specificity protein 1 by dibenzylideneacetone, a curcumin analogue,
      induces apoptosis in mucoepidermoid carcinomas and tumor xenografts through Bim
      and truncated Bid.
AB  - OBJECTIVES: Dibenzylideneacetone (DBA), a curcumin analogue that has anti-cancer
      activity in a variety of tumor cells. In this study, we investigated the
      apoptotic effects of DBA and its molecular mechanism in human mucoepidermoid
      carcinoma (MEC) cell lines and tumor xenografts. MATERIAL AND METHODS: The
      apoptotic effects and related molecular mechanisms of DBA on MEC cell lines were
      evaluated using cell viability assay, DAPI staining, Western blot analysis,
      reverse transcriptase-polymerase chain reaction (RT-PCR) and Dual-luciferase
      Reporter Assay. The anti-tumor activity using in vivo were determined by Nude
      mouse xenograft assay and histopathological examination. RESULTS: DBA decreased
      cell viability and induced apoptosis in MEC cells. These events were accompanied
      by inhibition of specificity protein 1 (Sp1). DBA did not induce major changes in
      Sp1 mRNA and promoter activity. Furthermore, inhibition of protein synthesis by
      cycloheximide demonstrated that DBA decreased Sp1 protein stability, but DBA did
      not attenuate phosphorylation of eIF4E. DBA also increased Bim and truncated Bid
      (t-Bid) via Sp1. Finally, DBA exhibited significant anti-tumor activity in
      athymic nude mice xenografts bearing MC-3 cells by regulating Sp1, Bim and t-Bid
      without any systemic toxicity. CONCLUSION: These results elucidate a crucial
      apoptotic mechanism of DBA and suggest that DBA may be a potent anticancer drug
      candidate for MEC.

PMID- 24309155
TI  - Sensitivity of freshwater pulmonate snail Lymnaea luteola L., to silver
      nanoparticles.
AB  - Toxicity of nanoparticles depends on many factors including size, shape, chemical
      composition, surface area and surface charge. Silver nanoparticles (AgNPs) are
      likely to enter the aquatic ecosystems because of their multiple applications and
      pose a health concern for humans and aquatic species. Therefore, we used a
      freshwater snail Lymnaea luteola L (L. luteola) to investigate the acute toxicity
      and genotoxicity of AgNPs in a static-renewal system for 96 h. AgNPs caused
      molluscicidal activity in L. luteola, with 96-h median lethal concentrations
      (LC50) (48.10 MUg L(-1)). We have observed that AgNPs (36 MUg L(-1)) elicited a
      significant (p<0.01) reduction in glutathione, glutathione-s-transferase and
      glutathione peroxidase with a concomitant increase in malondialdehyde level and
      catalase in digestive gland of L. luteola. However, a significant (p<0.01)
      induction in DNA damage was observed by the alkaline single cell gel
      electrophoresis in digestive gland cells treated with AgNPs for 24 and 96 h.
      These results demonstrate that silver nanoparticles are lethal to freshwater
      snail L. luteola. The oxidative stress biomarkers and comet assay can
      successfully be used as sensitive tools of aquatic pollution biomonitoring.

PMID- 24309156
TI  - Phthalate ester leachates in aquatic mesocosms: implications for ecotoxicity
      studies of endocrine disrupting compounds.
AB  - Aquatic mesocosm experiments have become common throughout the fields of ecology
      and ecotoxicology. Mesocosm containers are often composed of plastic materials as
      these are lighter and cheaper than steel cattle tanks. Plastics may contain
      phthalate esters which may leach from containers, potentially confounding
      experiments via toxicity or endocrine disruption. The objective of this
      experiment was to determine the extent to which plastic containers (="tanks")
      used for mesocosms leach phthalates, and if there are significant differences
      between tank types and phthalate profiles. We investigated four tank types:
      fiberglass, polyethylene, poly-vinyl chloride, and polyethylene tanks containing
      an established aquatic community. We measured six common phthalate esters in
      water samples collected from each tank every 2 weeks for 8 weeks. There was a
      significant effect of tank type, time, and time x type interactions on phthalate
      ester concentrations. Di-(2-ethylhexyl) phthalate was the predominant congener
      measured in all samples. Fiberglass tanks had greater concentrations of dimethyl
      phthalate compared to other tank types (more than 600x larger concentration), but
      no other differences in phthalate profiles among tank types were evident. In
      addition, tanks with established communities had much higher concentrations of
      most phthalates at the 6 and 8 week timepoints. Our study confirms that mesocosm
      tanks of different materials leach phthalates starting immediately after they are
      filled and continuing for at least 8 weeks, but do so at different rates. Future
      ecotoxicity experiments should consider the potentially confounding effects of
      phthalates that may leach from tanks used in experimental mesocosms.

PMID- 24309157
TI  - Smallanthus macroscyphus: a new source of antidiabetic compounds.
AB  - The aim of the present study was to analyze the in vivo hypoglycaemic effects of
      both decoction of Smallanthus macroscyphus leaves and pure crystalline polymatin
      A isolated from its leaves. Phytochemical analysis of the leaf decoction showed
      that its major constituents were caffeic, chlorogenic and three dicaffeoilquinic
      acids, together with the sesquiterpene lactone polymatin A. Oral glucose
      tolerance test in normal rats was performed to evaluate the hypoglycemic activity
      and to choose the minimum effective dose of the decoction and polymatin A. They
      have effective hypoglycemic activity at the minimum dose of 140 mg dry extract
      and 14 mg crystalline powder/kg body weight, respectively, and were selected for
      the following experiments. Oral administration of a single-dose of decoction
      produced a moderate lowering effect in fasting glycemia of normal rats, whereas
      polymatin A had no significant effect. We also assessed the effect of a single
      dose on post-prandial blood glucose, resulting in an inhibition of the
      hyperglycemic peak after sucrose overload. Daily administration of decoction or
      polymatin A for 4 weeks produced an effective glycemic control in diabetic
      animals, with a decrease in urinary glucose excretion and a significant reduction
      in the HbA1c levels. Although there were no significant increases in plasma
      insulin levels, both treatments improved the fasting blood glucose/insulin ratio.
      In vivo acute toxicity studies were performed in adult Wistar rats. There were no
      deaths or signs of toxicity observed after oral administration of decoction or
      polymatin A at any dose level up to the highest dose tested (14.0 and 2.8 g/kg,
      respectively). The results presented here strongly support the notion that S.
      macroscyphus represents a new source of antidiabetic compounds that could help to
      manage diabetes more efficiently and safely.

PMID- 24309158
TI  - Regulatory mechanism of gallic acid against advanced glycation end products
      induced cardiac remodeling in experimental rats.
AB  - Advanced glycation end products (AGEs) play a major role in the development of
      cardiovascular disorders in diabetic patients. Recent studies evidenced the
      beneficial role of phytochemicals in reducing the risk of cardiovascular
      diseases. Hence the present study was framed to investigate the protective role
      of Gallic acid (GA) on AGEs induced cardiac fibrosis. Rats were infused with in
      vitro prepared AGEs (50mg/kg BW-intravenous injection) for 30 days. Further, GA
      (25mg/kgBW) was administered to rats along with AGEs. On infusion of AGEs,
      induction of fibrotic markers, collagen deposition, oxidative marker NADPH
      oxidase (NOX-p47 phox subunit), AGE receptor (RAGE) and cytokines expression was
      evaluated in the heart tissues using RT-PCR, Western blot and immunostaining
      methods. AGEs infusion significantly (P<0.01) increased the HW/BW ratio and
      fibrosis (4-fold) with increased expression of matrix genes MMP-2 and -9 (P<0.01,
      respectively) in the heart tissues. Whereas, administration of GA along with AGEs
      infusion prevented the fibrosis induced by AGEs. Further, GA treatment
      effectively prevented the AGEs mediated up-regulation of pro-fibrotic genes and
      ECM proteins such as TNF-alpha, TGF-beta, MMP-2 and -9 expression. In addition,
      the increased expression of NOX (P<0.01), RAGE (P<0.01), NF-kappaB (P<0.01) and
      ERK 1/2 on AGEs infusion were normalized by GA treatment. Thus the present study
      shows the protective effect of GA on the fibrotic response and cardiac remodeling
      process induced by advanced glycation end products from external sources.

PMID- 24309159
TI  - Working memory in middle-aged males: age-related brain activation changes and
      cognitive fatigue effects.
AB  - We examined the effects of aging and cognitive fatigue on working memory (WM)
      related brain activation using functional magnetic resonance imaging. Age-related
      differences were investigated in 13 young and 16 middle-aged male school
      teachers. Cognitive fatigue was induced by sustained performance on cognitively
      demanding tasks (compared to a control condition). Results showed a main effect
      of age on left dorsolateral prefrontal and superior parietal cortex activation
      during WM encoding; greater activation was evident in middle-aged than young
      adults regardless of WM load or fatigue condition. An interaction effect was
      found in the dorsomedial prefrontal cortex (DMPFC); WM load-dependent activation
      was elevated in middle-aged compared to young in the control condition, but did
      not differ in the fatigue condition due to a reduction in activation in middle
      aged in contrast to an increase in activation in the young group. These findings
      demonstrate age-related activation differences and differential effects of
      fatigue on activation in young and middle-aged adults. 

PMID- 24309160
TI  - Frontal theta activity reflects distinct aspects of mental fatigue.
AB  - Longer lasting performance in cognitively demanding tasks leads to an exhaustion
      of cognitive resources and to a state commonly described as mental fatigue. More
      specifically, the allocation and focusing of attention become less efficient with
      time on task. Additionally, the selection of even simple responses becomes more
      error prone. With respect to the recorded EEG, mental fatigue has been reported
      to be associated with an increase in frontal theta and frontal and occipital
      alpha activity. The present study focused on the time course of changes in
      behavior and in the EEG to characterize fatigue-related processes. Participants
      performed a spatial stimulus-response-compatibility task in eight blocks for an
      overall duration of 4h. Error rates increased continuously with time on task.
      Total alpha power was larger at the end compared to the beginning of the
      experiment. However, alpha power increased rapidly and reached its maximal
      amplitude already after 1h, whereas frontal theta showed a continuous increase
      with time on task, possibly related to increased effort to keep the performance
      level high. Time frequency analyses revealed power changes in the theta band
      induced by task relevant information that might be assigned to a drain of
      executive control capacities. Thus, frontal theta turned out to be a reliable
      marker of distinct changes in cognitive processing with increasing fatigue. 

PMID- 24309161
TI  - Biotechnological potential of the fungal CTG clade species in the synthetic
      biology era.
AB  - Some of the fungal CTG clade species represent attractive yeast models in many
      aspects of biotechnology. Their particular codon usage has hindered the
      development of genetic approaches for exploring and exploiting their
      biotechnological potential. CTG clade yeast biotechnology now benefits from the
      establishment of versatile molecular toolboxes. In addition, a large range of
      rapidly evolving genomic and postgenomic approaches has recently enhanced the
      understanding of the architecture of CTG species metabolic networks. These
      represent essential prerequisites for further successful development of metabolic
      engineering in CTG yeasts by facilitating the design of synthetic pathways. 

PMID- 24309162
TI  - Smaller stress-sensitive hippocampal subfields in women with borderline
      personality disorder without posttraumatic stress disorder.
AB  - BACKGROUND: Animal and human studies have suggested that hippocampal subfields
      are differentially vulnerable to stress, but subfield volume has not been
      investigated in patients with borderline personality disorder (BPD). Based on the
      putative role of stressful life events as vulnerability factors for BPD, we
      hypothesized that patients with BPD would exhibit reduced volumes for the stress
      sensitive dentate gyrus (DG) and the cornu ammonis (CA) 3 subfields volumes, and
      that these volumes would be associated with traumatic childhood experiences.
      METHODS: All participants underwent 3 T magnetic resonance imaging. Hippocampal
      subfield volumes were estimated using an automated and validated segmentation
      algorithm implemented in FreeSurfer. Age and total subcortical grey matter volume
      were covariates. We assessed traumatic childhood experiences using the Childhood
      Trauma Questionnaire (CTQ). RESULTS: A total of 18 women with BPD and 21 healthy
      control women were included in the study. Only 1 patient had comorbid
      posttraumatic stress disorder (PTSD). The volumes of the left (p = 0.005) and
      right (p = 0.011) DG-CA4 and left (p = 0.007) and right (p = 0.005) CA2-3
      subfields were significantly reduced in patients compared with controls. We also
      found significant group differences for the left (p = 0.032) and right (p =
      0.028) CA1, but not for other hippocampal subfields. No associations were found
      between CTQ scores and subfield volumes. LIMITATIONS: The self-reported CTQ might
      be inferior to more comprehensive assessments of traumatic experiences. The
      sample size was moderate. CONCLUSION: The volumes of stress-sensitive hippocampal
      subfields are reduced in women with BPD without PTSD. However, the degree to
      which childhood trauma is responsible for these changes is unclear.

PMID- 24309163
TI  - [Rupture and migration of a reservoir catheter in the subclavian vein].

PMID- 24309164
TI  - Chronic intestinal ischemia due to multiple severe stenoses treated by
      endovascular surgery in a high risk patient.

PMID- 24309165
TI  - Hydatid thoracic spinal canal invasion.

PMID- 24309166
TI  - [Bouveret syndrome: variant of gallstone ileus].

PMID- 24309167
TI  - Time to rethink the neural mechanisms of learning and memory.
AB  - Most studies in the neurobiology of learning assume that the underlying learning
      process is a pairing - dependent change in synaptic strength that requires
      repeated experience of events presented in close temporal contiguity. However,
      much learning is rapid and does not depend on temporal contiguity, which has
      never been precisely defined. These points are well illustrated by studies
      showing that the temporal relations between events are rapidly learned- even over
      long delays- and that this knowledge governs the form and timing of behavior. The
      speed with which anticipatory responses emerge in conditioning paradigms is
      determined by the information that cues provide about the timing of rewards. The
      challenge for understanding the neurobiology of learning is to understand the
      mechanisms in the nervous system that encode information from even a single
      experience, the nature of the memory mechanisms that can encode quantities such
      as time, and how the brain can flexibly perform computations based on this
      information. 

PMID- 24309168
TI  - Langerhans cells in odontogenic epithelia of odontogenic fibromas.
AB  - BACKGROUND/PURPOSE: Langerhans cell (LC) is an antigen-presenting cell that is
      very important for T-cell-mediated immune reactions. Our previous studies have
      shown the presence of LCs in some odontogenic tumors and cysts. In this study, we
      further examined the presence of LCs in odontogenic epithelia of 16 odontogenic
      fibromas (OFs). METHODS: Anti-CD1a and anti-S-100 immunostains were used to
      detect the presence of LCs in nests or strands of odontogenic epithelia of 16
      OFs. RESULTS: These 16 OFs included 10 peripheral OFs excised from seven male and
      three female patients (mean age, 38 years) and six central OFs (including one
      recurrent OF) removed from five male patients (mean age, 28 years). Of the 10
      peripheral OFs, six were found on the mandibular gingiva and four on the
      maxillary gingiva. Four central OFs were located in the maxilla and two in the
      mandible. We found that both anti-CD1a and anti-S-100 immunostains had an equal
      ability to identify LCs in OFs. Positively stained dendritic LCs could be
      detected in nests and strands of odontogenic epithelia in nine (six peripheral
      and three central OFs) of the 16 OFs. In five peripheral OFs, dendritic LCs were
      found in occasional nests or strands of odontogenic epithelia. In one peripheral
      and three central OFs, dendritic LCs could be detected in at least half of the
      nests or strands of odontogenic epithelium in the tissue section. CONCLUSION: LCs
      can be detected in the nests or strands of odontogenic epithelia in approximately
      60% of the 10 peripheral OFs and approximately 50% of the six central OFs
      detected.

PMID- 24309169
TI  - Ultra-low dose (+)-naloxone restores the thermal threshold of morphine tolerant
      rats.
AB  - BACKGROUND/PURPOSE: As known, long-term morphine infusion leads to tolerance. We
      previously demonstrated that both co-infusion and post-administration of ultra
      low dose (+/-)-naloxone restores the antinociceptive effect of morphine in
      morphine-tolerant rats. However, whether the mechanism of the action of ultra-low
      dose (+/-)-naloxone is through opioid receptors or not. Therefore, in the present
      study, we further investigated the effect of ultra-low dose (+)-naloxone, it does
      not bind to opioid receptors, on the antinociceptive effect of morphine. METHODS:
      Male Wistar rats were implanted with one or two intrathecal (i.t.) catheters; one
      catheter was connected to a mini-osmotic pump, used for morphine (15 MUg/h),
      ultra-low dose (+)-naloxone (15 pg/h), morphine plus ultra-low dose (+)-naloxone
      (15 pg/h) or saline (1 MUl/h) infusion for 5 days. On day 5, either ultra-low
      dose (+)-naloxone (15 pg) or saline (5 MUl) was injected via the other catheter
      immediately after discontinued morphine or saline infusion. Three hours later,
      morphine (15 MUg in 5 MUl saline) or saline were given intrathecally. All rats
      received nociceptive tail-flick test every 30 minutes for 120 minutes after
      morphine challenge at different temperature (45-52 degrees C, respective).
      RESULTS: Our results showed that, both co-infusion and post-treatment of ultra
      low dose (+)-naloxone with morphine preserves the antinociceptive effect of
      morphine. Moreover, in the post administration rats, ultra-low dose (+)-naloxone
      further enhances the antinociceptive effect of morphine. CONCLUSION: This study
      provides an evidence for ultra-low dose (+)-naloxone as a therapeutic adjuvant
      for patients who need long-term opioid administration for pain management.

PMID- 24309170
TI  - Progression of stages 3b-5 chronic kidney disease--preliminary results of Taiwan
      national pre-ESRD disease management program in Southern Taiwan.
AB  - BACKGROUND/PURPOSE: The outcomes and their predictors, and rates of estimated
      glomerular filtration rate (eGFR) changes among Taiwanese, an ethnic Chinese
      population, with chronic kidney disease (CKD) stages 3b-5, enrolled in a
      nationwide pre-end-stage renal disease (pre-ESRD) management program that have
      not been previously reported. METHODS: This study focused on a cohort of patients
      enrolled in the Taiwan's pre-ESRD disease management program from Southern
      Taiwan, including 4061 CKD 3b-5 patients who received more than 12 weeks of
      follow-up from 2007 to 2010. The decline rates of eGFR, outcomes, and the
      predictors of initiating dialysis were analyzed. RESULTS: The study participants
      consisted of patients who were 70.1 +/- 12.3 years old, of whom 56.4% were male,
      46.3% were diabetic, and 72.1% were hypertensive. The mean annual eGFR changes
      were 0.47 +/- 0.42 mL/min/1.73 m(2)/year, -1.27 +/- 0.32 mL/min/1.73 m(2)/year,
      and -2.69 +/- 0.39 mL/min/1.73 m(2)/year for stages 3b, 4, and 5, respectively;
      however, more rapid declines were noted in diabetic patients. The Kaplan-Meier
      analyses revealed that the probabilities of patients remaining alive and free of
      dialysis treatment for CKD stage 3b, 4, and 5 without or with diabetes were
      89.46% versus 84.65%, 79.88% versus 55.68%, and 34.42% versus 9.64%,
      respectively, during 42 months of follow-up. Male gender, diabetes, lower
      baseline eGFR, higher systolic blood pressure, lower hematocrit, and albumin
      levels were the significant risk factors for initiating dialysis. CONCLUSION:
      Even though we cannot conclude with certainty that the Taiwan pre-ESRD disease
      management program is beneficial in slowing the progression of CKD stages 3b-5,
      our preliminary results seem to suggest this trend. Furthermore, the program may
      be improved by integrating it with other programs, such as those on diabetes and
      hypertension, thus making it a more patient-centered, multidisciplinary program.

PMID- 24309171
TI  - The impact of cigarette branding and plain packaging on perceptions of product
      appeal and risk among young adults in Norway: A between-subjects experimental
      survey.
AB  - OBJECTIVES: This study examined the perceptions of cigarette packaging and the
      potential impact of plain packaging regulations. The hypothesis was that the
      branded cigarette packages would be rated more positively than the corresponding
      plain packs with and without descriptors. DESIGN: Between-subjects experimental
      online survey. Male and female participants were separately randomised to one of
      the three experimental conditions: fully branded cigarette packs, plain packs
      with descriptors and plain packs without descriptors; participants were asked to
      evaluate 12 individual cigarette packages. The participants were also asked to
      compare five pairs of packs from the same brand family. SETTING: Norway.
      PARTICIPANTS: 1010 youths and adults aged 15-22. PRIMARY OUTCOME MEASURES:
      Ratings of appeal, taste and harmfulness for individual packages. Ratings of
      taste, harm, quality, 'would rather try' and 'easier to quit' for pairs of
      packages. RESULTS: Plain with and without descriptors packs were rated less
      positively than the branded packs on appeal (index score 1.63/1.61 vs 2.42,
      p<0.001), taste (index score 1.21/1.12 vs 1.70, p<0.001) and as less harmful
      (index score 1.0.34/0.36 vs 0.82, p<0.001) among females. Among males, the
      difference between the plain with and without descriptors versus branded
      condition was significant for appeal (index score 2.08/1.92 vs 2.58, p<0.005) and
      between the plain without descriptors versus branded condition for taste (index
      score 1.18 vs 1.70, p<0.00). The pack comparison task showed that the packs with
      descriptors suggesting a lower content of harmful substances, together with
      lighter colours, were more positively rated in the branded compared with the
      plain condition on dimensions less harmful (beta -0.77, 95% CI -0.97 to -0.56),
      would rather try (beta -0.32, 95% CI -0.50 to -0.14) and easier to quit (beta 
      0.58, 95% CI -0.76 to -0.39). CONCLUSIONS: The results indicate that a shift from
      branded to plain cigarette packaging could lead to a reduction in positive
      perceptions of cigarettes among young people.

PMID- 24309172
TI  - Evaluation of three-dose fosfomycin tromethamine in the treatment of patients
      with urinary tract infections: an uncontrolled, open-label, multicentre study.
AB  - OBJECTIVE: To evaluate the clinical and microbiological efficacy and safety of
      three doses of 3 g fosfomycin tromethamine administered orally to treat lower
      urinary tract infections. DESIGN AND PARTICIPANTS: This prospective,
      uncontrolled, open-label study was conducted in 12 medical centres in China,
      between January and December 2011. According to the diagnosis criteria of Chinese
      Guidelines on Urological Infections, patients (18-70 years) with acute
      uncomplicated cystitis, recurrent lower urinary tract infection or complicated
      lower urinary tract infection received three doses of 3 g fosfomycin tromethamine
      orally, at days 1, 3 and 5. PRIMARY AND SECONDARY OUTCOME MEASURES: Efficacy
      endpoints (clinical efficacy, microbiological efficacy and overall efficacy) were
      evaluated on day 15. Clinical symptoms, physical signs, urinalysis, liver and
      kidney function, patient records and evaluation of adverse events (AEs) and
      serious AEs up to day 15 were evaluated for analysis of safety. RESULTS: 361
      patients were included in the full analysis set, 356 in the safety analysis set
      and 335 in the per-protocol set (PPS). In the PPS, the clinical efficacy rates at
      day 15 for acute uncomplicated cystitis, recurrent lower urinary tract infection
      and complicated lower urinary tract infection were 94.71% (179/189), 77.22%
      (61/79) and 62.69% (42/67), respectively. The microbiological efficacy rates (day
      15) were 97.65% (83/85), 94.44% (34/36) and 83.87% (26/31), respectively. The
      overall efficacy rates (day 15) were 95.29% (81/85), 77.78% (28/36) and 64.52%
      (20/31), respectively. 20/356 (5.6%) patients reported drug-related AEs, the most
      common being diarrhoea. No serious drug-related AEs were reported. CONCLUSIONS:
      This fosfomycin tromethamine dosing regimen showed clinical and microbiological
      efficacy with some AEs and good tolerability in patients with acute uncomplicated
      cystitis, recurrent lower urinary tract infection and complicated lower urinary
      tract infection.

PMID- 24309173
TI  - Protocol for a qualitative study on promoting dietary change and positive food
      choices for poor people with low income who experience cardiovascular disease in
      Pakistan.
AB  - INTRODUCTION: There is a misconception that cardiovascular disease (CVD) is the
      burden of wealthy nations, but, in fact, it is the leading cause of death and
      disability-adjusted life worldwide. Healthy diets are an essential factor in the
      prevention of CVD. However, promoting healthy diet is challenging, particularly
      for people with low-socioeconomic status (SES), because poverty is linked with
      many risk behaviours such as smoking, unhealthy eating and obesity. Multiple
      factors, cultural values and beliefs interact and make healthy eating very
      challenging. The effects of these factors in the context of low-SES populations
      with CVD are largely unknown. To address this gap, this study will examine the
      factors that affect decisions about consuming healthy diet in Pakistanis with low
      SES who suffer from CVD. METHODS AND ANALYSIS: A qualitative method of
      interpretive description will be used. 25 participants will be selected from two
      cardiac rehabilitation (CR) centres in Karachi, Pakistan. Face-to-face interviews
      using a critical realist framework will be used to understand individual and
      contextual factors in the food choices of people with low SES and CVD. ATLAS.ti
      qualitative data analysis software will be used to identify themes and patterns
      in the interview data. ETHICS AND DISCUSSION: Ethical approvals were received
      from the Ethics Review board of University of Alberta, Canada and Aga Khan
      University, Karachi Pakistan. The findings will generate new knowledge about
      which and how factors influence the food choices of Pakistanis with CVD and low
      SES to provide an insight into the development of an operational framework for
      designing interventions for prevention of CVD. For knowledge-translation
      purposes, we will publish the findings in highly accessed, peer-reviewed
      scientific and health policy journals at the national and international level.
      This research protocol received IRDC (International Development Research Centre)
      doctoral award from International Development Research Centre, Ottawa, Canada.

PMID- 24309174
TI  - Do healthier foods and diet patterns cost more than less healthy options? A
      systematic review and meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis of prices of
      healthier versus less healthy foods/diet patterns while accounting for key
      sources of heterogeneity. DATA SOURCES: MEDLINE (2000-2011), supplemented with
      expert consultations and hand reviews of reference lists and related citations.
      DESIGN: Studies reviewed independently and in duplicate were included if
      reporting mean retail price of foods or diet patterns stratified by
      healthfulness. We extracted, in duplicate, mean prices and their uncertainties of
      healthier and less healthy foods/diet patterns and rated the intensity of health
      differences for each comparison (range 1-10). Prices were adjusted for inflation
      and the World Bank purchasing power parity, and standardised to the international
      dollar (defined as US$1) in 2011. Using random effects models, we quantified
      price differences of healthier versus less healthy options for specific food
      types, diet patterns and units of price (serving, day and calorie). Statistical
      heterogeneity was quantified using I(2) statistics. RESULTS: 27 studies from 10
      countries met the inclusion criteria. Among food groups, meats/protein had
      largest price differences: healthier options cost $0.29/serving (95% CI $0.19 to
      $0.40) and $0.47/200 kcal ($0.42 to $0.53) more than less healthy options. Price
      differences per serving for healthier versus less healthy foods were smaller
      among grains ($0.03), dairy (-$0.004), snacks/sweets ($0.12) and fats/oils
      ($0.02; p<0.05 each) and not significant for soda/juice ($0.11, p=0.64).
      Comparing extremes (top vs bottom quantile) of food-based diet patterns,
      healthier diets cost $1.48/day ($1.01 to $1.95) and $1.54/2000 kcal ($1.15 to
      $1.94) more. Comparing nutrient-based patterns, price per day was not
      significantly different (top vs bottom quantile: $0.04; p=0.916), whereas price
      per 2000 kcal was $1.56 ($0.61 to $2.51) more. Adjustment for intensity of
      differences in healthfulness yielded similar results. CONCLUSIONS: This meta
      analysis provides the best evidence until today of price differences of healthier
      vs less healthy foods/diet patterns, highlighting the challenges and
      opportunities for reducing financial barriers to healthy eating.

PMID- 24309175
TI  - Computational studies on the anastrozole and letrozole, effective chemotherapy
      drugs against breast cancer.
AB  - In this paper, computational studies were carried out on anastrozole and
      letrozole, chemotherapy drugs used against breast cancer. Optimization and
      frequency calculations were performed at B3LYP/6-31G (d) basis set and
      vibrational frequencies were assignment. Single point calculations were performed
      at DFT method with a hybrid functional B3LYP/6-311G (d, p) basis set. Theoretical
      NMR data were obtained at DFT method with a hybrid functional B3LYP/6-311G++ (2d,
      p) with GIAO (Gauge-Independent Atomic Orbital). IEF-PCM method was used as
      solvation model. NBO calculations were performed by the same basis set and
      calculation method with single point calculation. Global and localized reactivity
      parameters; fukui indices (f) chemical hardness (eta), softness (S), chemical
      potential (MU), electronegativity (chi) and electrophilicity index (omega) were
      calculated. All computational parameters were compared with the experimental
      results obtained from the literature. 

PMID- 24309176
TI  - Spectrophotometric and high performance liquid chromatographic methods for
      sensitive determination of bisphenol A.
AB  - A new spectrophotometric method for the determination of trace amounts of
      bisphenol A based on a diazotization-coupling reaction was developed. In acidic
      solution, clenbuterol was first diazotized with sodium nitrite, then coupled with
      bisphenol A to from an azo-compound [I] in NH3-NH4Cl buffer, which shows a
      maximum absorption at 410 nm. The effects of the amount of sodium nitrite, diazo
      reaction time, the amount of clenbuterol, coupling reaction time and coupling
      reaction temperature have been examined. Under the optional conditions, the
      determination of the linear range of bisphenol A is 0.24-8.4 MUg/mL, correlation
      coefficient is 0.9905 and detection limit of this method is 0.15 MUg/mL. The
      spectrophotometric method is simple, rapid, high sensitivity with better
      accuracy. High performance liquid chromatography (HPLC) technique combined with
      this new spectrophotometric method has been also developed for the measurement of
      bisphenol A. The analysis was achieved on a C18 column using water and methanol
      as a mobile phase and the detection was done spectrophotometrically at 410 nm.
      These reported methods were applied to the determination of bisphenol A in hot
      water in contact with commercially available table-water bottle samples.

PMID- 24309177
TI  - Fluorescence and nonradiative processes of dioxin vapors.
AB  - Fluorescence, fluorescence excitation, biacetyl-sensitized phosphorescence
      excitation and absorption spectra of five dioxins (dibenzofuran, 2
      chlirodibenzofuran, 2,8-dichlorodibenzofuran, dibenzo-p-dioxin and 2
      chlorodibenzo-p-dioxin) have been measured in the vapor phase. The intersystem
      crossing yields of dioxin vapors have been determined by means of a biacetyl
      sensitized phosphorescence method. It is shown that the nonradiative rates from
      the S1 state of dibenzo-p-dioxins increase significantly with increasing
      excitation energy, while those of dibenzofurans are almost unchanged. It is also
      shown that the main nonradiative process from S1 for dibenzofurans is both the
      intersystem crossing to T1 and internal conversion to S0 which includes possible
      photodecomposition, while that for dibenzo-p-dioxins is the internal conversion
      to S0, which also may include possible photochemical decomposition processes. 

PMID- 24309178
TI  - Investigation on the inclusion and toxicity of acriflavine with cyclodextrins: a
      spectroscopic approach.
AB  - Acriflavine hydrochloride (AFN) is a prospective drug worn in the eradication of
      HIV1 infection. The toxicity and adverse side effects renders the potent drug to
      limits its usage. However, to overcome the dilemma we have aimed to select
      carriers with great complexation efficiencies in different cyclodextrins (CDs) of
      varying cavity size. The interaction of AFN with alpha, beta and gamma-CDs were
      investigated using absorption and steady state as well as lifetime measurements.
      From the obtained data it was found that AFN fits in the cavity of alpha and beta
      CDs but unable to form inclusion complex with gamma-CD. The effect of quencher
      molecules during the inclusion phenomena of AFN with CDs was explored via steady
      state measurements. The nature of binding forces responsible for the inclusion of
      AFN with CDs was discussed by using thermodynamic parameters. Using Benesi
      Hildebrand equation the stoichiometry of AFN with CDs was predominantly found to
      be 1:1. To get deeper in situ, the in vitro toxicity of AFN and its complexation
      product were probed by Artemia salina sp. The toxicity of AFN was reduced when
      complexed with alpha and beta-CDs. 

PMID- 24309179
TI  - Spectroscopic analysis, structural, microstructural, optical and electrical
      properties of Zn-doped In2O3 thin films.
AB  - In this work, highly transparent conducting un-doped and Zn-doped In2O3 thin
      films were prepared onto glass substrate using spray pyrolysis method.
      Structural, morphological, optical and electrical properties were characterized
      by using XRD, FT-IR, FT-Raman, SEM, AFM, UV-visible, PL and Hall Effect
      measurement techniques. X-ray diffraction analysis showed that the deposited
      films were polycrystalline with cubic structure having (222) as preferred
      orientation. SEM and AFM analyses showed smooth surfaces but the surface
      roughness of the films increased due to Zn doping. The average optical
      transmittance of the films was above 94% in the visible range. The optical band
      gap decreased from 3.62 to 3.28 eV with increasing Zn concentration. The
      photoluminescence spectra displayed violet-blue emission peaks at around 418-440
      nm for all films. The electrical parameters like the resistivity, mobility and
      carrier concentration were found as 6.4*10(-4) Omega cm, 168 cm(2)/Vs and
      9.4*10(20) cm(-3), respectively for In2O3:Zn film deposited at 9 at.%. The
      present results showed that the obtained thin films could be used as an
      optoelectronic material.

PMID- 24309180
TI  - New 3,4-diaminobenzoic acid Schiff base compounds and their complexes: synthesis,
      characterization and thermodynamics.
AB  - Some new tetradentate Schiff base ligands (H3L) were prepared via condensation of
      3,4-diaminobenzoic acid with 2-hydroxybenzaldehyde derivatives, such as 3,4
      bis((E)-2,4-dihydroxybenzylideneamino)benzoic acid (H3L(1)), 3,4-bis((E)-2
      hydroxy-3-methoxybenzylideneamino)benzoic acid (H3L(2)) and 3,4-bis((E)-5-bromo-2
      hydroxybenzylideneamino)benzoic acid (H3L(4)). Additionally, a tetradentate
      Schiff base ligand 3,4-bis((E)-2-hydroxybenzylideneamino)benzoic acid (H3L(3))
      and its complexes were synthesized. Their metal complexes of Co(II), Ni(II),
      Cu(II) and Zn(II) were prepared in good yields from the reaction of the ligands
      with the corresponding metal acetate. They were characterized based on IR, (1)H
      NMR, Mass spectroscopy and UV-Vis spectroscopy. Also, the formation constants of
      the complexes were measured by UV-Vis spectroscopic titration at constant ionic
      strength 0.1M (NaClO4), at 25  degrees C in dimethylformamide (DMF) as a solvent.

PMID- 24309181
TI  - Palladium nanoparticles synthesized by reducing species generated during a
      successive acidic/alkaline treatment of sucrose.
AB  - Uniform spherical palladium nanoparticles with an average particle size of 4.3+/
      0.5 nm were successfully synthesized by reducing H2PdCl4 with intermediates in
      situ generated during a successive acidic/alkaline treatment of sucrose. A
      successive acidic/alkaline treatment plays an important role on converting the
      non-reducing sucrose into efficient reducing species containing aldehyde
      functionality. The Benedict's test corroborates the development and vanishing of
      the in situ generated reducing species upon prolonged degradation. An increase in
      alkalinity drastically improves the reduction efficiency. ATR FT-IR spectroscopy
      indicated spontaneous development of carboxylate after the alkaline treatment.
      Under the employed condition, small organic species with carbonyl groups
      (aldehyde, acid, and acid salt) were generated through the sucrose degradation
      before being oxidized to carbonate after an hour of the treatment. Sucrose was
      completely decomposed into carbonate after a 24-h successive acidic/alkaline
      treatment. The synthesized palladium nanoparticles express a good catalytic
      activity in the decolorization process of Congo red by sodium borohydride.

PMID- 24309182
TI  - c-Fos mediates repression of the apical sodium-dependent bile acid transporter by
      fibroblast growth factor-19 in mice.
AB  - Fibroblast growth factor-19 (FGF-19), a bile acid-responsive enterokine, is
      secreted by the ileum and regulates a variety of metabolic processes. These
      studies examined the signal transduction pathways operant in FGF-19-mediated
      repression of the apical sodium-dependent bile acid transporter (ASBT). Responses
      to FGF-19 were assessed in Caco-2 and CT-26 cells and in mice where c-fos was
      conditionally silenced in the intestine by a cre-lox strategy. FGF-19 treatment
      of Caco-2 cells or wild-type mice led to a significant reduction in ASBT protein
      expression and enhanced phosphorylation of extracellular signaling kinase 1/2
      (ERK1/2), c-Fos, and c-Jun. FGF-19 treatment of Caco-2 cells led to a reduction
      in activity of the human ASBT promoter and this repression could be blocked by
      treatment with a mitogen-activated protein kinase/ERK kinase (MEK1/2) inhibitor
      or by silencing jun kinase 1, jun kinase 2, c-fos, or c-jun. Site directed
      mutagenesis of a c-fos binding element in the ASBT promoter blocked FGF-19
      mediated repression in luciferase reporter constructs. ASBT promoter activity was
      repressed by FGF-19 in CT-26 cells and this repression could be reduced by MEK1/2
      inhibition or silencing c-fos. FGF-19-mediated repression of ASBT protein
      expression was abrogated in mice where c-fos was conditionally silenced in the
      intestine. In contrast, ASBT was repressed in the c-Fos expressing gallbladders
      of the same mice. The studies demonstrate that FGF-19 represses the expression of
      ASBT in the ileum and gallbladder via a signal transduction pathway involving
      MEK1/2, ERK1/2, JNK1, JNK2, and c-Fos. 

PMID- 24309183
TI  - Glucocorticoids regulate barrier function and claudin expression in intestinal
      epithelial cells via MKP-1.
AB  - Barrier dysfunction is pivotal to the pathogenesis of inflammatory bowel diseases
      (IBD) and collagenous colitis. Glucocorticoids restore barrier function in
      Crohn's disease, but whether this reflects attenuated inflammation or an
      epithelial-specific action has not yet been addressed. Using filter-grown Caco-2
      monolayers as an in vitro model of the intestinal epithelial barrier, we observed
      that glucocorticoids induced a time- and dose-dependent increase in
      transepithelial electrical resistance (TEER) in a glucocorticoid receptor
      dependent manner without altering flux of larger solutes or changing principal
      tight junction architecture. This was accompanied by reduced paracellular cation
      flux, reduced expression of the pore-forming tight junction component claudin-2,
      and upregulation of the sealing tight junction protein claudin-4. In contrast,
      expression of occludin, claudin-1, -7, or -8 was not altered. Dexamethasone
      increased expression and activity of MAPK phosphatase-1 and inhibition of this
      phosphatase prevented the glucocorticoid-induced changes in TEER and claudin
      expression, whereas inhibiting p38 or MEK1/2 was not sufficient to replicate the
      glucocorticoid effects. Upon exposure to IFN-gamma, TNF-alpha, or IL-1beta, TEERs
      declined in dexamethasone-treated cells but remained consistently higher than in
      cells not receiving glucocorticoids. Treatment with IFN/TNF resulted in an
      upregulation of claudin-2 that was significantly attenuated by dexamethasone,
      whereas increased claudin-2 expression upon IL-1beta stimulation was not affected
      by glucocorticoids. Taken together, barrier augmentation might represent a
      previously unrecognized mechanism of action, potentially contributing to the
      therapeutic efficacy of glucocorticoids in IBD and collagenous colitis. 

PMID- 24309184
TI  - Two-photon microscopy reveals stationary podocytes in living zebrafish larvae.
AB  - Podocytes are an essential component of the glomerular filtration barrier and
      cover the outer aspect of glomerular capillaries. They form a complex actin-based
      cytoskeleton in vivo and show prominent motility in vitro, but whether podocytes
      are stationary or mobile in vivo is debated. To address this question, the
      pronephros of translucent zebrafish larvae (casper) expressing enhanced green
      fluorescent protein (eGFP) specifically in podocytes (wt1a:eGFP larvae) was
      observed by intravital two-photon microscopy over extended periods of time.
      Podocyte cell bodies and the interdigitating branching pattern of major processes
      could be resolved with a resolution of approximately 1 um in the xy-plane. Time
      lapse imaging of zebrafish larvae at 5-7 days after fertilization demonstrated
      that podocytes neither migrated nor changed the branching pattern of their major
      processes over a time period of up to 23 hours. In summary, we show by extended
      intravital two-photon microscopy that podocytes are stationary cells in the
      intact glomerulus of a translucent zebrafish with fluorescently-labeled
      podocytes. 

PMID- 24309185
TI  - The kidney as a reservoir for HIV-1 after renal transplantation.
AB  - Since the recent publication of data showing favorable outcomes for patients with
      HIV-1 and ESRD, kidney transplantation has become a therapeutic option in this
      population. However, reports have documented unexplained reduced allograft
      survival in these patients. We hypothesized that the unrecognized infection of
      the transplanted kidney by HIV-1 can compromise long-term allograft function.
      Using electron microscopy and molecular biology, we examined protocol renal
      transplant biopsies from 19 recipients with HIV-1 who did not have detectable
      levels of plasma HIV-1 RNA at transplantation. We found that HIV-1 infected the
      kidney allograft in 68% of these patients. Notably, HIV-1 infection was detected
      in either podocytes predominately (38% of recipients) or tubular cells only (62%
      of recipients). Podocyte infection associated with podocyte apoptosis and loss of
      differentiation markers as well as a faster decline in allograft function
      compared with tubular cell infection. In allografts with tubular cell infection,
      epithelial cells of the proximal convoluted tubules frequently contained abnormal
      mitochondria, and both patients who developed features of subclinical acute
      cellular rejection had allografts with tubular cell infection. Finally, we
      provide a novel noninvasive test for determining HIV-1 infection of the kidney
      allograft by measuring HIV-1 DNA and RNA levels in patients' urine. In
      conclusion, HIV-1 can infect kidney allografts after transplantation despite
      undetectable viremia, and this infection might influence graft outcome. 

PMID- 24309186
TI  - Macrophage dynamics in AKI to CKD progression.

PMID- 24309187
TI  - Remote ischemic preconditioning and renoprotection: from myth to a novel
      therapeutic option?
AB  - There is currently no effective prophylactic regimen available to prevent
      contrast-induced AKI (CI-AKI), a frequent and life-threatening complication after
      cardiac catheterization. Therefore, novel treatment strategies are required to
      decrease CI-AKI incidence and to improve clinical outcomes in these patients.
      Remote ischemic preconditioning (rIPC), defined as transient brief episodes of
      ischemia at a remote site before a subsequent prolonged ischemia/reperfusion
      injury of the target organ, is an adaptational response that protects against
      ischemic and reperfusion insult. Indeed, several studies demonstrated the tissue
      protective effects of rIPC in various target organs, including the kidneys. In
      this regard, rIPC may offer a novel noninvasive and virtually cost-free treatment
      strategy for decreasing CI-AKI incidence. This review evaluates the current
      experimental and clinical evidence for rIPC as a potential renoprotective
      strategy, and discusses the underlying mechanisms and key areas for future
      research. 

PMID- 24309188
TI  - Macrophage phenotype controls long-term AKI outcomes--kidney regeneration versus
      atrophy.
AB  - The mechanisms that determine full recovery versus subsequent progressive CKD
      after AKI are largely unknown. Because macrophages regulate inflammation as well
      as epithelial recovery, we investigated whether macrophage activation influences
      AKI outcomes. IL-1 receptor-associated kinase-M (IRAK-M) is a macrophage-specific
      inhibitor of Toll-like receptor (TLR) and IL-1 receptor signaling that prevents
      polarization toward a proinflammatory phenotype. In postischemic kidneys of wild
      type mice, IRAK-M expression increased for 3 weeks after AKI and declined
      thereafter. However, genetic depletion of IRAK-M did not affect immunopathology
      and renal dysfunction during early postischemic AKI. Regarding long-term
      outcomes, wild-type kidneys regenerated completely within 5 weeks after AKI. In
      contrast, IRAK-M(-/-) kidneys progressively lost up to two-thirds of their
      original mass due to tubule loss, leaving atubular glomeruli and interstitial
      scarring. Moreover, M1 macrophages accumulated in the renal interstitial
      compartment, coincident with increased expression of proinflammatory cytokines
      and chemokines. Injection of bacterial CpG DNA induced the same effects in wild
      type mice, and TNF-alpha blockade with etanercept partially prevented renal
      atrophy in IRAK-M(-/-) mice. These results suggest that IRAK-M induction during
      the healing phase of AKI supports the resolution of M1 macrophage- and TNF-alpha
      dependent renal inflammation, allowing structural regeneration and functional
      recovery of the injured kidney. Conversely, IRAK-M loss-of-function mutations or
      transient exposure to bacterial DNA may drive persistent inflammatory mononuclear
      phagocyte infiltrates, which impair kidney regeneration and promote CKD. Overall,
      these results support a novel role for IRAK-M in the regulation of wound healing
      and tissue regeneration. 

PMID- 24309189
TI  - Longitudinal changes in estimated and measured GFR in type 1 diabetes.
AB  - Estimation of GFR from serum concentrations of creatinine and cystatin C has been
      refined using cross-sectional data from large numbers of people. However, the
      ability of the improved estimating equations to identify changes in GFR within
      individuals over time has not been rigorously evaluated, particularly within the
      normal range of GFR. In cross-sectional and longitudinal analyses of 1441
      participants in the Diabetes Control and Complications Trial (DCCT)/Epidemiology
      of Diabetes Interventions and Complications (EDIC) study with type 1 diabetes, we
      compared GFR estimated from creatinine (eGFR(Cr)), cystatin C (eGFR(Cys)), or
      both (eGFR(Cr+Cys)) with iothalamate GFR (iGFR), including changes in each over
      time. Mean (SD) iGFR was 122.7 (21.0) ml/min per 1.73 m(2). In cross-sectional
      analyses, eGFR(Cr+Cys) estimated iGFR with the highest correlation (r=0.48 versus
      0.39-0.42), precision, and accuracy. In longitudinal analyses, change in
      eGFR(Cr+Cys) best estimated change in iGFR; however, differences between
      estimates were small, and no estimate accurately classified change in iGFR. Over
      a median 23 years of follow-up, mean rate of change in eGFR was similar across
      estimates of eGFR(Cr), eGFR(Cys), and eGFR(Cr+Cys) (-1.37, -1.11, and -1.29
      ml/min per 1.73 m(2) per year, respectively). Associations of BP and hemoglobin
      A1c with change in eGFR were strongest for eGFR(Cys) and eGFR(Cr+Cys). Together,
      these results suggest that the addition of cystatin C to creatinine to estimate
      GFR may improve identification of the causes and consequences of GFR loss in type
      1 diabetes, but may not meaningfully improve the tracking of GFR in clinical
      care.

PMID- 24309191
TI  - Kidney infection with HIV-1 following kidney transplantation.

PMID- 24309190
TI  - Genetics of new-onset diabetes after transplantation.
AB  - New-onset diabetes after transplantation is a common complication that reduces
      recipient survival. Research in renal transplant recipients has suggested that
      pancreatic beta-cell dysfunction, as opposed to insulin resistance, may be the
      key pathologic process. In this study, clinical and genetic factors associated
      with new-onset diabetes after transplantation were identified in a white
      population. A joint analysis approach, with an initial genome-wide association
      study in a subset of cases followed by de novo genotyping in the complete case
      cohort, was implemented to identify single-nucleotide polymorphisms (SNPs)
      associated with the development of new-onset diabetes after transplantation.
      Clinical variables associated with the development of diabetes after renal
      transplantation included older recipient age, female sex, and percentage weight
      gain within 12 months of transplantation. The genome-wide association study
      identified 26 SNPs associated with new-onset diabetes after transplantation; this
      association was validated for eight SNPs (rs10484821, rs7533125, rs2861484,
      rs11580170, rs2020902, rs1836882, rs198372, and rs4394754) by de novo genotyping.
      These associations remained significant after multivariate adjustment for
      clinical variables. Seven of these SNPs are associated with genes implicated in
      beta-cell apoptosis. These results corroborate recent clinical evidence
      implicating beta-cell dysfunction in the pathophysiology of new-onset diabetes
      after transplantation and support the pursuit of therapeutic strategies to
      protect beta cells in the post-transplant period. 

PMID- 24309192
TI  - Extensive functional pleiotropy of REVOLUTA substantiated through forward
      genetics.
AB  - In plants, genes may sustain extensive pleiotropic functional properties by
      individually affecting multiple, distinct traits. We discuss results from three
      genome-wide association studies of approximately 400 natural poplar (Populus
      trichocarpa) accessions phenotyped for 60 ecological/biomass, wood quality, and
      rust fungus resistance traits. Single-nucleotide polymorphisms (SNPs) in the
      poplar ortholog of the class III homeodomain-leucine zipper transcription factor
      gene REVOLUTA (PtREV) were significantly associated with three specific traits.
      Based on SNP associations with fungal resistance, leaf drop, and cellulose
      content, the PtREV gene contains three potential regulatory sites within
      noncoding regions at the gene's 3' end, where alternative splicing and messenger
      RNA processing actively occur. The polymorphisms in this region associated with
      leaf abscission and cellulose content are suggested to represent more recent
      variants, whereas the SNP associated with leaf rust resistance may be more
      ancient, consistent with REV's primary role in auxin signaling and its functional
      evolution in supporting fundamental processes of vascular plant development. 

PMID- 24309193
TI  - Regioselective dehydrogenation of 3-keto-steroids to form conjugated enones using
      o-iodoxybenzoic acid and trifluoroacetic acid catalysis.
AB  - Mild and regioselective conversion of 3-keto-5alpha- and 3-keto-5beta-steroids
      (trans A/B- and cis A/B-ring juncture, respectively) to the corresponding enones
      (Delta(1)- and Delta(4)-3-ketones) by treatment with o-iodoxybenzoic acid (IBX)
      catalyzed by trifluoroacetic acid (TFA) in DMSO, is described. The IBX-mediated
      reaction involved dehydrogenation of the alpha- and beta-hydrogen atoms of the 3
      ketones to give the enones regioselectively in good isolated yields without
      concomitant formation of related dienones and trienones. 

PMID- 24309194
TI  - Influence of nanoparticle-membrane electrostatic interactions on membrane
      fluidity and bending elasticity.
AB  - The aim of this work is to investigate the effect of electrostatic interactions
      between the nanoparticles and the membrane lipids on altering the physical
      properties of the liposomal membrane such as fluidity and bending elasticity. For
      this purpose, we have used nanoparticles and lipids with different surface
      charges. Positively charged iron oxide (gamma-Fe2O3) nanoparticles, neutral and
      negatively charged cobalt ferrite (CoFe2O4) nanoparticles were encapsulated in
      neutral lipid 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine and negatively
      charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine lipid mixture.
      Membrane fluidity was assessed through the anisotropy measurements using the
      fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. Though the interaction of both
      the types of nanoparticles reduced the membrane fluidity, the results were more
      pronounced in the negatively charged liposomes encapsulated with positively
      charged iron oxide nanoparticles due to strong electrostatic attractions. X-ray
      photoelectron spectroscopy results also confirmed the presence of significant
      quantity of positively charged iron oxide nanoparticles in negatively charged
      liposomes. Through thermally induced shape fluctuation measurements of the giant
      liposomes, a considerable reduction in the bending elasticity modulus was
      observed for cobalt ferrite nanoparticles. The experimental results were
      supported by the simulation studies using modified Langevin-Poisson-Boltzmann
      model. 

PMID- 24309195
TI  - Phosphatidylinositol-4,5-bisphosphate ionization in the presence of cholesterol,
      calcium or magnesium ions.
AB  - Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) is an important signaling lipid
      and plays a crucial role in a wide variety of cellular processes by interacting
      with protein targets and localizing proteins at the plasma membrane. These
      interactions are strongly influenced by the lateral distribution of PI(4,5)P2 as
      well as its ionization state. The characterization of the PI(4,5)P2 ionization
      state provides important information about how PI(4,5)P2 interacts with other
      membrane resident or associated chemical species. In this study we have used
      solid-state MAS (31)P NMR to investigate the interactions of PI(4,5)P2 with
      potential cluster promoting agents, divalent cations and cholesterol. Both Ca(2+)
      and cholesterol were found previously to promote formation of local PI(4,5)P2
      clusters in vitro. The NMR approach allows us to probe independently the
      ionization state of PI(4,5)P2 two phosphomonoester groups. We investigated mixed
      phosphatidylcholine (PC)/PI(4,5)P2 multilamellar vesicles in the presence of
      micro and millimolar concentrations of Ca(2+) and Mg(2+). We found that both
      cations lead to an increased downfield chemical shift of the PI(4,5)P2
      phosphomonoester peaks, indicating an increased ionization in the presence of the
      divalent cations. Ca(2+) has a much larger effect on PI(4,5)P2 as compared to
      Mg(2+) at similar concentrations. Physiological concentrations of Ca(2+) are
      significantly lower than those found for Mg(2+) and the comparison of the
      PI(4,5)P2 ionization in the presence of Ca(2+) and Mg(2+) at physiological
      concentrations resulted in similar charges of the phosphomonoester groups for
      both cations. PI(4,5)P2 was also examined with vesicles containing cholesterol
      since cholesterol has been shown to promote PI(4,5)P2 clustering. In the presence
      of 40 mol% cholesterol, the PI(4,5)P2 phosphomonoester (31)P NMR peaks shifted
      slightly downfield, indicating a small increase in charge. Previously published
      data suggest that PI(4,5)P2 is capable of forming an intra- and intermolecular
      hydrogen bond network, which leads to a reduction of the charge at the
      phosphomonoester groups through dissipation of the charge across the
      bilayer/water interface. We hypothesize that cholesterol participates in this
      intermolecular hydrogen bond network, resulting in a stabilization of PI(4,5)P2
      enriched domains due an increased spacing between the PI(4,5)P2 headgroup. We
      also examined the cumulative effects of cholesterol combined with the divalent
      cations, phosphatidylethanolamine (PE), and phosphatidylinositol (PI),
      separately. The combination of cholesterol and divalent cations results in an
      additive effect on PI(4,5)P2 ionization, while the effect of cholesterol on
      PI(4,5)P2 ionization is reduced in the presence of PE or PI.

PMID- 24309196
TI  - Energy drinks and alcohol: links to alcohol behaviors and consequences across 56
      days.
AB  - PURPOSE: To examine short-term consequences associated with consuming alcohol and
      energy drinks compared with consuming alcohol without energy drinks. METHODS: A
      longitudinal measurement-burst design (14-day bursts of daily surveys in four
      consecutive college semesters) captured both within-person variation across
      occasions and between-person differences across individuals. The analytic sample
      of late adolescent alcohol users included 4,203 days with alcohol use across up
      to four semesters per person from 508 college students. RESULTS: Adding energy
      drink use to a given day with alcohol use was associated with an increase in
      number of alcoholic drinks, a trend toward more hours spent drinking, elevated
      estimated blood alcohol content (eBAC), a greater likelihood of subjective
      intoxication, and more negative consequences of drinking that day. After
      controlling for eBAC, energy drink use no longer predicted subjective
      intoxication but was still associated with a greater number of negative
      consequences. CONCLUSIONS: The consumption of energy drinks may lead to increases
      in alcohol consumption and, after controlling for eBAC, negative consequences.
      Use of energy drinks plus alcohol represents an emerging threat to public health.

PMID- 24309197
TI  - Outcome analysis of liver stiffness by ARFI (acoustic radiation force impulse)
      elastometry in patients with chronic viral hepatitis B and C.
AB  - AIM: To evaluate the association between liver stiffness measured by acoustic
      radiation force impulse (ARFI) elastometry and the outcome of antiviral treatment
      in patients with chronic viral hepatitis B and C. MATERIALS AND METHODS: Thirty
      eight patients with chronic viral hepatitis B (n = 16) or hepatitis C (n = 22)
      underwent liver biopsy and ARFI elastometry of the right hepatic lobe. A follow
      up assessment using ARFI was performed a mean of 2.3 years after the baseline
      evaluation. The patients with favourable outcome were classified in group S and
      those receiving no treatment, showing no response to treatment, or experiencing a
      relapse were classified in group N. RESULTS: The 38 patients had an initial mean
      ARFI value of 1.56 +/- 0.62 m/s as compared with 1.54 +/- 0.64 m/s in the follow
      up evaluation. Group S showed a significant decline in ARFI values (1.55 +/- 0.60
      m/s versus 1.34 +/- 0.47 m/s; p < 0.05) and included 16 (64%) patients with lower
      shear wave velocities at follow-up. In group N, liver stiffness values showed a
      slight but not significant increase (1.57 +/- 0.70 m/s versus 1.93 +/- 0.77 m/s).
      CONCLUSION: Changes in liver stiffness during antiviral therapy can be assessed
      by ARFI reflecting response or no response. ARFI elastometry is an additional,
      useful tool for the follow-up assessment of treatment outcome in patients with
      chronic viral hepatitis B or C infection.

PMID- 24309198
TI  - A high-dose preparation of lactobacilli and bifidobacteria in the prevention of
      antibiotic-associated and Clostridium difficile diarrhoea in older people
      admitted to hospital: a multicentre, randomised, double-blind, placebo
      controlled, parallel arm trial (PLACIDE).
AB  - BACKGROUND: Antibiotic-associated diarrhoea (AAD) occurs most commonly in older
      people admitted to hospital and within 12 weeks of exposure to broad-spectrum
      antibiotics. Although usually a mild and self-limiting illness, the 15-39% of
      cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)]
      may result in severe diarrhoea and death. Previous research has shown that
      probiotics, live microbial organisms that, when administered in adequate numbers,
      are beneficial to health, may be effective in preventing AAD and CDD. OBJECTIVES:
      To determine the clinical effectiveness and cost-effectiveness of a high-dose,
      multistrain probiotic in the prevention of AAD and CDD in older people admitted
      to hospital. DESIGN: A multicentre, randomised, double-blind, placebo-controlled,
      parallel-arm trial. SETTING: Medical, surgical and elderly care inpatient wards
      in five NHS hospitals in the UK. PARTICIPANTS: Eligible patients were aged >= 65
      years, were exposed to one or more oral or parenteral antibiotics and were
      without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic
      adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited.
      Participants were allocated sequentially according to a computer-generated random
      allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488
      (49.9%) to the placebo arm. INTERVENTIONS: Vegetarian capsules containing two
      strains of lactobacilli and two strains of bifidobacteria (a total of 6 * 10(10)
      organisms per day) were taken daily for 21 days. The placebo was inert
      maltodextrin powder in identical capsules. MAIN OUTCOME MEASURES: The occurrence
      of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by
      participant follow-up and checking hospital laboratory records by research nurses
      who were blind to arm allocation. RESULTS: Analysis based on the treatment
      allocated included 2941 (98.7%) participants. Potential risk factors for AAD at
      baseline were similar in the two study arms. Frequency of AAD (including CDD) was
      similar in the probiotic (159/1470, 10.8%) and placebo arms [153/1471, 10.4%;
      relative risk (RR) 1.04; 95% confidence interval (CI) 0.84 to 1.28; p = 0.71].
      CDD was an uncommon cause of AAD and occurred in 12/1470 (0.8%) participants in
      the probiotic and 17/1471 (1.2%) in the placebo arm (RR 0.71; 95% CI 0.34 to
      1.47; p = 0.35). Duration and severity of diarrhoea, common gastrointestinal
      symptoms, serious adverse events and quality of life measures were also similar
      in the two arms. Total health-care costs per patient did not differ significantly
      between the probiotic (L8020; 95% CI L7620 to L8420) and placebo (L8010; 95% CI
      L7600 to L8420) arms. CONCLUSION: We found no evidence that probiotic
      administration was effective in preventing AAD. Although there was a trend
      towards reduced CDD in the probiotic arm, on balance, the administration of this
      probiotic seems unlikely to benefit older patients exposed to antibiotics. A
      better understanding of the pathogenesis of AAD and CDD and the strain-specific
      effects of probiotics is needed before further clinical trials of specific
      microbial preparations are undertaken. Evaluation of the effectiveness of other
      probiotics will be difficult where other measures, such as antibiotic
      stewardship, have reduced CDD rates. TRIAL REGISTRATION: This trial is registered
      as ISRCTN70017204. FUNDING: This project was funded by the NIHR Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 17, No. 57. See the NIHR Journals Library website for further
      project information.

PMID- 24309199
TI  - International data-sharing for radiotherapy research: an open-source based
      infrastructure for multicentric clinical data mining.
AB  - Extensive, multifactorial data sharing is a crucial prerequisite for current and
      future (radiotherapy) research. However, the cost, time and effort to achieve
      this are often a roadblock. We present an open-source based data-sharing
      infrastructure between two radiotherapy departments, allowing seamless exchange
      of de-identified, automatically translated clinical and biomedical treatment
      data. 

PMID- 24309200
TI  - [Validity of the Keith Edwards scoring system for the diagnosis of childhood
      pulmonary tuberculosis].
AB  - INTRODUCTION: The diagnosis of childhood pulmonary tuberculosis remains a
      challenge. The effectiveness of the Keith Edwards scoring system used to diagnose
      tuberculosis is controversial. We evaluated this scoring system in the present
      study. METHODS: A prospective randomized study was conducted between March 2008
      and December 2011 at the Kimpese General Evangelical Hospital in the Democratic
      Republic of Congo. The results of the Keith Edwards score were considered for the
      161 children (100 pulmonary tuberculosis and 61 case controls) who were enrolled
      in the study. The association between different parameters and the score and
      between these parameters and pulmonary tuberculosis were statistically analyzed
      using univariate and multivariate tests. RESULTS: Eighty-five (85%) out of the
      100 children diagnosed as having pulmonary tuberculosis and 20 (32.8%) of the
      case controls had a positive score. The age of the patient, duration of the
      disease, nutritional status, tuberculosis contact, positive tuberculin skin test,
      and lymph node enlargement showed a significant statistical association with the
      score and pulmonary tuberculosis (P<0.05). The score's sensitivity and
      specificity were 85% and 67.2%, respectively. The positive predictive value and
      negative predictive value were found to be 80.9% and 73.2%, respectively. The
      positive likelihood ratio was 2.57, the negative likelihood ratio was 0.22, and
      overall agreement was 76.1%. CONCLUSION: The Keith Edwards score could be good
      tool for public health purposes, but it might be less effective for individual
      diagnosis of childhood pulmonary tuberculosis because of low specificity. Further
      studies are required to evaluate and validate the diagnostic value of clinical
      and radiological symptoms in childhood pulmonary tuberculosis.

PMID- 24309201
TI  - [Cardiovascular risks and management during Attention Deficit Hyperactivity
      Disorder treatment with methylphenidate].
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common of the
      pediatric neuropsychiatric disorders. Methylphenidate is an important element of
      therapeutic strategies for ADHD. Clinicians are interested in the safety of
      methylphenidate. Because this drug raises heart rate and blood pressure, concerns
      have been raised about its cardiovascular safety. Concerns were based on case
      reports of sudden cardiac death in methylphenidate users, plausible
      pharmacological pathways involving well-established stimulant effects on heart
      rate and blood pressure. Until recently, data were limited to a number of
      observational studies too small to examine serious cardiac events. In the past
      two years, large retrospective, population-based cohort studies were performed.
      These studies did not show any evidence that methylphenidate was associated with
      an increase in risk of myocardial infarction, sudden cardiac death, or stroke.
      Treatment of children with methylphenidate is not significantly associated with
      an increase in the short term or mid-term risk of severe cardiac events. For
      many, available data now will be seen as reassuring. But gaps persist in the
      methodical and comprehensive assessments of the safety of methylphenidate.
      Analyses cannot be generalized to children with long-term use of stimulants.
      Furthermore, long-term effects of slight increases in heart rate or blood
      pressure are unknown. Stimulant administration continues to have a detectable
      adrenergic effect even after years of treatment. In the MTA study, greater
      cumulative stimulant exposure was associated with a higher heart rate at years 3
      and 8. Although less severe, such adverse cardiac events are nonetheless alarming
      to patients. This adrenergic effect may have clinical implications, especially
      for individual patients with underlying heart abnormalities and it deserves
      further investigation. More research is necessary to optimize a safe use of
      methylphenidate regarding its cardiovascular effects. In light of the
      controversies surrounding the increase in the number of children being diagnosed
      with ADHD, the broad use of methylphenidate in these patients, and cardiovascular
      concerns about it, this article addresses topics of clinical significance. For
      ease of use by practitioners, the article summarizes the guidelines stated by the
      European Medicines Agency over the appropriate pretreatment evaluation and
      cardiovascular assessment. It advocates a thorough history and physical
      examination before initiating methylphenidate to treat patients with ADHD, with
      an emphasis on the identification of risk factors for sudden death. A cardiac sub
      specialist consultation is mandatory in case of history or physical examination
      findings. In other cases, an electrocardiographic screening is recommended in
      order to check out previously unrecognized heart disease. 

PMID- 24309202
TI  - [National consensus regarding the prescription of inhaled corticosteroids in
      cystic fibrosis].
AB  - The conditions for the prescription of inhaled steroids (ISs) in cystic fibrosis
      (CF) are not well established. AIM: To propose a formalized consensus agreement
      regarding the prescription of ISs in this disease. MATERIAL AND METHODS:
      Application of the Delphi method in five thematic fields: indications, non
      indications, dosage, precautions for use, and treatment follow-up. RESULTS:
      Thirty of forty-nine (61 %) reference CF centers in France participated in the
      process, which comprised three rounds. Experts strongly agreed that ISs are
      indicated in the presence of pulmonary manifestations with wheezing, personal
      history of atopy, and/or bronchial hyper-responsiveness. In contrast, ISs are not
      indicated as first-line therapy for allergic bronchopulmonary aspergillosis.
      Strong agreement was reached regarding the daily dose of ISs, which should be
      similar to what is given in asthma and adapted to control symptoms so as to
      prescribe the smallest possible dose. Increasing the frequency of bacterial and
      fungal sputum analyses and eye (cataract) assessments was not deemed necessary.
      However, in case of prolonged (>6months) use of high-dose ISs, monitoring bone
      mineral density and the hypothalamic-pituitary-adrenal axis, in particular if
      itraconazole is concomitantly prescribed, was recommended. CONCLUSION: This
      consensus statement defines a perimeter for the prescription of ISs in CF, with
      the aim of limiting their prescription (until new data are available).

PMID- 24309203
TI  - A bibliometric analysis of the 100 most influential papers in burns.
AB  - The importance of a published paper to a particular area is reflected in the
      quantity of citations obtained from peers. In burns, it is unknown which papers
      have been the most influential on this specialty. The purpose of our study was to
      identify the 100 most cited papers in burns and to analyze their characteristics.
      Twenty-seven journals were chosen for analysis. These included high impact factor
      scientific journals and journals dedicated to burns and trauma. Only twelve of
      these journals contributed to the 100 most cited papers in burns and we analyzed
      each paper individually looking at its subject matter, authorship, article type,
      institution, country and year of publication. Our citation analysis revealed an
      interesting mix of clinical and scientific papers that documents the key
      landmarks in burn care over the past 66 years. 

PMID- 24309204
TI  - Predicting post-electrical injury autonomic dysfunction symptom occurrence by a
      simple test.
AB  - BACKGROUND: Sensory, motor, and autonomic neuropathy has been reported after
      electrical injury. Besides subclinical involvement of the sympathetic nervous
      system during the 1st year post injury, late clinical manifestations of this
      involvement have been reported sporadically. This study was designed to
      investigate how the clinical and electrodiagnostic manifestations of sympathetic
      involvement would change with time in electricity victims. METHODS AND MATERIALS:
      Sixty electrically burnt patients were followed for 22 months with sympathetic
      skin response (SSR) and autonomic system derangement symptom surveillance.
      RESULTS: Thirty-one patients reported autonomic derangement symptoms during the
      2nd year post injury. SSR latency prolongation showed direct negative correlation
      with time; but SSR amplitude was decreased in all cases irrespective of the time
      laps. Symptomatic patients showed significantly lower SSR amplitudes compared to
      asymptomatic ones. This was true for the pre-symptom SSR test results too.
      CONCLUSION: SSR amplitude can be used as a predictive test for the symptoms of
      autonomic derangement to occur post electrical injury.

PMID- 24309205
TI  - Dkk3 levels in patients with myeloproliferative neoplasms.
AB  - INTRODUCTION: Dickkopf-3 (Dkk3) has been proposed as tumor suppressor gene and a
      marker for tumor blood vessels and has pro-angiogenic properties. Dkk3 is
      expressed in platelets and megakaryocytes from healthy controls and patients with
      BCR-ABL1-negative myeloproliferative neoplasms (MPN). The aim of this study is,
      to find out whether patients with MPN have higher Dkk3 serum levels than normal
      controls. MATERIAL & METHODS: We analyzed Dkk3 serum levels with ELISA in
      patients with newly diagnosed and untreated MPN, including 10 essential
      thrombocythemia (ET), 10 polycythemia vera (PV), 10 primary meylofibrosis (PMF)
      and 10 healthy blood donors and correlated these findings with biological and
      clinical key data and the JAK2-V617F status. Dkk3 levels were corrected to
      platelet count, Dkk3c, as patients with MPN have higher platelet counts than
      controls. RESULTS: As expected, patients with MPN have higher platelet counts
      than normal controls. Dkk3 serum levels of patients with MPN (5.4 +/- 6.1 ng/ml)
      showed no significant difference compared to normal controls (4.4 +/- 3.8 ng/ml).
      Regarding Dkk3c, a significant difference to controls was found in PV (8.5 +/-
      8.7 ng/ml; p=0.04), but not in ET and PMF (5.7 +/- 3.8 ng/ml; p=0.07 and 2.7 +/-
      3.6 ng/ml; p=0.9; respectively. Dkk3c correlated with the JAK2-V617F mutational
      burden (p=0.014, Rho=0.445). CONCLUSION: Dkk3 levels corrected to platelet count
      showed higher levels in PV than normal controls. Elevated Dkk3c level could
      possibly correlate to platelet activation in PV patients and increased Dkk3
      release. Whether this remains a surrogate marker of platelet release or it
      contributes to the thrombophilic state through its pro-angiogenic properties
      remains to be shown.

PMID- 24309206
TI  - Mixed infection by Legionella pneumophila in outbreak patients.
AB  - During the molecular epidemiological study of a legionellosis outbreak, we
      obtained sequence based typing (SBT) profiles from uncultured respiratory samples
      of 15 affected patients. We detected several distinct allelic profiles some of
      which were a mixture of alleles present in the more common profiles.
      Chromatograms from the sequences of one patient with mixed profile showed
      polymorphisms in several positions, which could result from the simultaneous
      presence of different Legionella variants in the sample. In order to test this
      possibility, we cloned PCR amplification products from six loci for two patients
      with a mixed profile and a patient with a pure profile. After obtaining around 20
      sequences for each locus of three patients, we detected several variants in two
      of them and two variants in the third one. In summary, the three analyzed
      patients showed evidence of more than one Legionella variant during the acute
      infection. These results indicate that probably some patients were infected by
      more than one strain, which could be due to co-infection from the same
      environmental source or, alternatively, to independent infections in a very short
      period of time. Although our data cannot discriminate between these hypotheses,
      these results suggest that Legionella infection patterns can be more complex than
      previously assumed. None of the environmental samples analyzed during this
      outbreak was even similar to any of the clinical ones. 

PMID- 24309207
TI  - Hydration dependence of myoglobin dynamics studied with elastic neutron
      scattering, differential scanning calorimetry and broadband dielectric
      spectroscopy.
AB  - In this work we present a thorough investigation of the hydration dependence of
      myoglobin dynamics. The study is performed on D2O-hydrated protein powders in the
      hydration range 0<h<0.5 (h=gr[D2O]/gr[protein]) and in the temperature range 20
      300K. The protein equilibrium fluctuations are investigated with Elastic Neutron
      Scattering using the spectrometer IN13 at ILL (Grenoble), while the relaxations
      of the protein+hydration water system are investigated with Broadband Dielectric
      Spectroscopy; finally, Differential Scanning Calorimetry is used to obtain a
      thermodynamic description of the system. The effect of increasing hydration is to
      speed up the relaxations of the myoglobin+hydration water system and,
      thermodynamically, to decrease the glass transition temperature; these effects
      tend to saturate at h values greater than ~0.3. Moreover, the calorimetric scans
      put in evidence the occurrence of an endothermic peak whose onset temperature is
      located at ~230K independent of hydration. From the point of view of the protein
      equilibrium fluctuations, while the amplitude of anharmonic mean square
      displacements is found to increase with hydration, their onset temperature (i.e.
      the onset temperature of the well known "protein dynamical transition") is
      hydration independent. On the basis of the above results, the relevance of
      protein+hydration water relaxations and of the thermodynamic state of hydration
      water to the onset of the protein dynamical transition is discussed. 

PMID- 24309208
TI  - Wnt/beta-catenin signaling in dermal condensates is required for hair follicle
      formation.
AB  - Broad dermal Wnt signaling is required for patterned induction of hair follicle
      placodes and subsequent Wnt signaling in placode stem cells is essential for
      induction of dermal condensates, cell clusters of precursors for the hair
      follicle dermal papilla (DP). Progression of hair follicle formation then
      requires coordinated signal exchange between dermal condensates and placode stem
      cells. However, it remains unknown whether continued Wnt signaling in DP
      precursor cells plays a role in this process, largely due to the long-standing
      inability to specifically target dermal condensates for gene ablation. Here we
      use the Tbx18(Cre) knockin mouse line to ablate the Wnt-responsive transcription
      factor beta-catenin specifically in these cells at E14.5 during the first wave of
      guard hair follicle formation. In the absence of beta-catenin, canonical Wnt
      signaling is effectively abolished in these cells. Sox2(+) dermal condensates
      initiate normally; however by E16.5 guard hair follicle numbers are strongly
      reduced and by E18.5 most whiskers and guard hair follicles are absent,
      suggesting that active Wnt signaling in dermal condensates is important for hair
      follicle formation to proceed after induction. To explore the molecular
      mechanisms by which Wnt signaling in dermal condensates regulates hair follicle
      formation, we analyze genome-wide the gene expression changes in embryonic beta
      catenin null DP precursor cells. We find altered expression of several signaling
      pathway genes, including Fgfs and Activin, both previously implicated in hair
      follicle formation. In summary, these data reveal a functional role of Wnt
      signaling in DP precursors for embryonic hair follicle formation and identify Fgf
      and Activin signaling as potential effectors of Wnt signaling-regulated events. 

PMID- 24309210
TI  - Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis.
AB  - The tumor suppressor p53 is thought to play a role in megakaryocyte (MK)
      development. To assess the influence of the p53 regulatory pathway further, we
      studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53
      by preventing its interaction with MDM2, on normal megakaryocytopoiesis and
      platelet production. This drug has been previously been evaluated in clinical
      trials of cancer patients where thrombocytopenia was one of the major dose
      limiting toxicities. In this study, we demonstrated that administration of RG7112
      in vivo in rats and monkeys results in thrombocytopenia. In addition, we
      identified two distinct mechanisms by which RG7112-mediated activation of p53
      affected human megakaryocytopoiesis and platelet production in vitro. RG7112
      promoted apoptosis of MK progenitor cells, resulting in a reduction of their
      numbers and RG7112 affected mature MK by blocking DNA synthesis during
      endomitosis and impairing platelet production. Together, the disruption of these
      events provides an explanation for RG7112-induced thrombocytopenia and insight
      into the role of the p53-MDM2 auto-regulatory loop in normal
      megakaryocytopoiesis.

PMID- 24309209
TI  - Zebrafish nephrogenesis is regulated by interactions between retinoic acid,
      mecom, and Notch signaling.
AB  - The zebrafish pronephros provides a conserved model to study kidney development,
      in particular to delineate the poorly understood processes of how nephron segment
      pattern and cell type choice are established. Zebrafish nephrons are divided into
      distinct epithelial regions that include a series of proximal and distal tubule
      segments, which are comprised of intercalated transporting epithelial cells and
      multiciliated cells (MCC). Previous studies have shown that retinoic acid (RA)
      regionalizes the renal progenitor field into proximal and distal domains and that
      Notch signaling later represses MCC differentiation, but further understanding of
      these pathways has remained unknown. The transcription factor mecom (mds1/evi1
      complex) is broadly expressed in renal progenitors, and then subsequently marks
      the distal tubule. Here, we show that mecom is necessary to form the distal
      tubule and to restrict both proximal tubule formation and MCC fate choice. We
      found that mecom and RA have opposing roles in patterning discrete proximal and
      distal segments. Further, we discovered that RA is required for MCC formation,
      and that one mechanism by which RA promotes MCC fate choice is to inhibit mecom.
      Next, we determined the epistatic relationship between mecom and Notch signaling,
      which limits MCC fate choice by lateral inhibition. Abrogation of Notch signaling
      with the gamma-secretase inhibitor DAPT revealed that Notch and mecom did not
      have additive effects in blocking MCC formation, suggesting that they function in
      the same pathway. Ectopic expression of the Notch signaling effector, Notch
      intracellular domain (NICD), rescued the expansion of MCCs in mecom morphants,
      indicating that mecom acts upstream to induce Notch signaling. These findings
      suggest a model in which mecom and RA arbitrate proximodistal segment domains,
      while MCC fate is modulated by a complex interplay in which RA inhibition of
      mecom, and mecom promotion of Notch, titrates MCC number. Taken together, our
      studies have revealed several essential and novel mechanisms that control
      pronephros development in the zebrafish. 

PMID- 24309211
TI  - Neuronal merlin influences ERBB2 receptor expression on Schwann cells through
      neuregulin 1 type III signalling.
AB  - Axonal surface proteins encompass a group of heterogeneous molecules, which exert
      a variety of different functions in the highly interdependent relationship
      between axons and Schwann cells. We recently revealed that the tumour suppressor
      protein merlin, mutated in the hereditary tumour syndrome neurofibromatosis type
      2, impacts significantly on axon structure maintenance in the peripheral nervous
      system. We now report on a role of neuronal merlin in the regulation of the
      axonal surface protein neuregulin 1 important for modulating Schwann cell
      differentiation and myelination. Specifically, neuregulin 1 type III expression
      is reduced in sciatic nerve tissue of neuron-specific knockout animals as well as
      in biopsies from seven patients with neurofibromatosis type 2. In vitro
      experiments performed on both the P19 neuronal cell line and primary dorsal root
      ganglion cells demonstrate the influence of merlin on neuregulin 1 type III
      expression. Moreover, expression of ERBB2, a Schwann cell receptor for neuregulin
      1 ligands is increased in nerve tissue of both neuron-specific merlin knockout
      animals and patients with neurofibromatosis type 2, demonstrating for the first
      time that axonal merlin indirectly regulates Schwann cell behaviour.
      Collectively, we have identified that neuronally expressed merlin can influence
      Schwann cell activity in a cell-extrinsic manner. 

PMID- 24309212
TI  - Synergistic interaction between ankle and knee during hopping revealed through
      induced acceleration analysis.
AB  - The forces produced by the muscles can deliver energy to a target segment they
      are not attached to, by transferring this energy throughout the other segments in
      the chain. This is a synergistic way of functioning, which allows muscles to
      accelerate or decelerate segments in order to reach the target one. The purpose
      of this study was to characterize the contribution of each lower extremity joint
      to the vertical acceleration of the body's center of mass during a hopping
      exercise. To accomplish this, an induced acceleration analysis was performed
      using a model with eight segments. The results indicate that the strategies
      produced during a hopping exercise rely on the synergy between the knee and ankle
      joints, with most of the vertical acceleration being produced by the knee
      extensors, while the ankle plantar flexors act as stabilizers of the foot. This
      synergy between the ankle and the knee is perhaps a mechanism that allows the
      transfer of power from the knee muscles to the ground, and we believe that in
      this particular task the net action of the foot and ankle moments is to produce a
      stable foot with little overall acceleration. 

PMID- 24309213
TI  - Sample prefractionation with liquid isoelectric focusing enables in depth
      microbial metaproteome analysis of mesophilic and thermophilic biogas plants.
AB  - Biogas production from energy crops and biodegradable waste is one of the major
      sources for renewable energies in Germany. Within a biogas plant (BGP) a complex
      microbial community converts biomass to biogas. Unfortunately, disturbances of
      the biogas process occur occasionally and cause economic losses of varying
      extent. Besides technical failures the microbial community itself is commonly
      assumed as a reason for process instability. To improve the performance and
      efficiency of BGP, a deeper knowledge of the composition and the metabolic state
      of the microbial community is required and biomarkers for monitoring of process
      deviations or even the prediction of process failures have to be identified.
      Previous work based on 2D-electrophoresis demonstrated that the analysis of the
      metaproteome is well suited to provide insights into the apparent metabolism of
      the microbial communities. Using SDS-PAGE with subsequent mass spectrometry,
      stable protein patterns were evaluated for a number of anaerobic digesters.
      Furthermore, it was shown that severe changes in process parameters such as
      acidification resulted in significant modifications of the metaproteome.
      Monitoring of changing protein patterns derived from anaerobic digesters,
      however, is still a challenge due to the high complexity of the metaproteome. In
      this study, different combinations of separation techniques to reduce the
      complexity of proteomic BGP samples were compared with respect to the subsequent
      identification of proteins by tandem mass spectrometry (MS/MS): (i) 1D: proteins
      were tryptically digested and the resulting peptides were separated by reversed
      phase chromatography prior to MS/MS. (ii) 2D: proteins were separated by GeLC
      MS/MS according to proteins molecular weights before tryptic digestion, (iii) 3D:
      proteins were separated by gel-free fractionation using isoelectric focusing
      (IEF) conducted before GeLC-MS/MS. For this study, a comparison of two anaerobic
      digesters operated at mesophilic and at thermophilic conditions was conducted.
      The addition of further separation dimensions before protein identification
      increased the number of identified proteins. On the other hand additional
      fractionation steps increased the experimental work load and the time required
      for LC-MS/MS measurement. The high resolution of the 3D-approach enabled the
      detection of approximately 750 to 1650 proteins covering the main pathways of
      hydrolysis, acidogenesis, acetogenesis and methanogenesis. Methanosarcinales
      dominated in the mesophilic BGP, whereas Methanomicrobiales were highly abundant
      in the thermophilic BGP. Pathway analysis confirmed the taxonomic results and
      revealed that the acetoclastic methanogenesis occurred preferentially at
      mesophilic conditions, whereas exclusively hydrogenotrophic methanogenesis was
      detected in thermophilic BGP. However, for the identification of process
      biomarkers by comprehensive screening of BGP it will be indispensable to find a
      balance between the experimental efforts and analytical resolution. 

PMID- 24309214
TI  - Toxigenic genes, spoilage potential, and antimicrobial resistance of Bacillus
      cereus group strains from ice cream.
AB  - Bacillus spp. can be recovered from almost every environment. It is also found
      readily in foods, where it may cause food spoilage and/or food poisoning due to
      its toxigenic and pathogenic nature, and extracellular enzymes. In this study, 29
      Bacillus cereus group strains from ice cream were examined for the presence of
      following virulence genes hblC, nheA, cytK and ces genes, and tested for a range
      of the extracellular enzymes, and antimicrobial susceptibility. The strains were
      found to produce extracellular enzymes: proteolytic and lipolytic activity,
      gelatin hydrolysis and lecithinase production (100%), DNase production (93.1%)
      and amylase activity (93.1%). Of 29 strains examined, 24 (82.8%) showed hemolytic
      activity on blood agar. Beta-lactamase enzyme was only produced by 20.7% of B.
      cereus group. Among 29 B. cereus group from ice cream, nheA was the most common
      virulence gene detected in 44.8% of the strains, followed by hblC gene with
      17.2%. Four (13.8%) of the 29 strains were positive for both hblC gene and nheA
      gene. Contrarily, cytK and ces genes were not detected in any of the strains.
      Antimicrobial susceptibility of ice cream isolates was tested to 14 different
      antimicrobial agents using the disc diffusion method. We detected resistance to
      penicillin and ampicillin with the same rate of 89.7%. Thirty-one percent of the
      strains were multiresistant to three or more antibiotics. This study emphasizes
      that the presence of natural isolates of Bacillus spp. harboring one or more
      enterotoxin genes, producing extracellular enzymes which may cause spoilage and
      acquiring antibiotic resistance might hold crucial importance in the food safety
      and quality. 

PMID- 24309215
TI  - Quantitative imaging biomarkers for the evaluation of cardiovascular
      complications in type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is a prevalent condition in aged populations.
      Cardiovascular diseases are leading causes of death and disability in patients
      with T2DM. Traditional strategies for controlling the cardiovascular
      complications of diabetes primarily target a cluster of well-defined risk
      factors, such as hyperglycemia, lipid disorders and hypertension. However, there
      is controversy over some recent clinical trials aimed at evaluating efficacy of
      intensive treatments for T2DM. As a powerful tool for quantitative cardiovascular
      risk estimation, multi-disciplinary cardiovascular imaging have been applied to
      detect and quantify morphological and functional abnormalities in the
      cardiovascular system. Quantitative imaging biomarkers acquired with advanced
      imaging procedures are expected to provide new insights to stratify absolute
      cardiovascular risks and reduce the overall costs of health care for people with
      T2DM by facilitating the selection of optimal therapies. This review discusses
      principles of state-of-the-art cardiovascular imaging techniques and compares
      applications of those techniques in various clinical circumstances. Individuals
      measurements of cardiovascular disease burdens from multiple aspects, which are
      closely related to existing biomarkers and clinical outcomes, are recommended as
      promising candidates for quantitative imaging biomarkers to assess the responses
      of the cardiovascular system during diabetic regimens. 

PMID- 24309216
TI  - Mechanisms involved in increased sensitivity to adenosine A(2A) receptor
      activation and hypoxia-induced vasodilatation in porcine coronary arteries.
AB  - Hypoxia-induced coronary vasorelaxation is a compensatory mechanism increasing
      blood flow. We hypothesized that hypoxia shares pathways with adenosine and
      causes vasorelaxation through the adenosine A(2A) receptor and force suppression
      by increasing cAMP and phosphorylated heat shock protein (HSP)20. Adenosine
      receptors in porcine left anterior descending coronary arteries (LAD) were
      examined by RT-PCR and isometric tension recording in myographs. Vasorelaxation
      was induced by adenosine, 1% oxygen, or both in the absence or presence of
      ZM241385, an adenosine A(2A) receptor antagonist. cAMP was determined by ELISA
      and p-HSP20/HSP20 and p-MLC/MLC were determined by immunoblotting and
      densitometric analyses. In coronary arteries exposed to 1% oxygen, there was
      increased sensitivity to adenosine, the adenosine A2 selective agonist NECA, and
      the adenosine A(2A) selective receptor agonist CGS21680. ZM241385 shifted
      concentration-response curves for CGS21680 to the right, whereas the adenosine A1
      antagonist DPCPX, the adenosine A2B receptor antagonist MRS1754 and the adenosine
      A3 receptor antagonist MRS1523 failed to reduce vasodilatation induced by
      CGS21680. 1% oxygen or adenosine increased cAMP accumulation and HSP20
      phosphorylation without changing T850-MYPT1 and MLC phosphorylation. ZM241385
      failed to change 1% oxygen-induced vasodilation, cAMP accumulation, HSP20
      phosphorylation and MLC phosphorylation. The PKA inhibitor Rp-8-CPT-cAMPS
      significantly reduced vasorelaxation induced by 1% oxygen or CGS21680. Our
      findings suggest that the increased sensitivity to adenosine, NECA, and CGS21680
      at 1% oxygen involves adenosine A(2A) receptors. Adenosine and 1% oxygen induce
      vasorelaxation in PGF2alpha-contracted porcine coronary arteries partly by force
      suppression caused by increased cAMP and phosphorylation of HSP20.

PMID- 24309217
TI  - The novel dipeptidyl peptidase-4 inhibitor teneligliptin prevents high-fat diet
      induced obesity accompanied with increased energy expenditure in mice.
AB  - Dipeptidyl peptidase-4 (DPP-4)-deficient mice exhibit prevention of obesity with
      increased energy expenditure, whereas currently available DPP-4 inhibitors do not
      induce similar changes. We investigated the impact of the novel DPP-4 inhibitor
      teneligliptin on body weight, energy expenditure, and obesity-related
      manifestations in diet-induced obese mice. Six-weeks-old C57BL/6N mice were fed a
      high-fat diet (60%kcal fat) ad libitum and administered teneligliptin (30 or
      60mg/kg) via drinking water for 10 weeks. Mice fed a high-fat diet showed
      accelerated body weight gain. In contrast, compared with the vehicle group, the
      administration of teneligliptin reduced body weight to 88% and 71% at dose of
      30mg/kg/day and 60mg/kg/day, respectively. Although there was no change in
      locomotor activity, indirect calorimetry studies showed that teneligliptin
      (60mg/kg) increased oxygen consumption by 22%. Adipocyte hypertrophy and hepatic
      steatosis induced by a high-fat diet were suppressed by teneligliptin. The mean
      adipocyte size in the 60-mg/kg treatment group was 44% and hepatic triglyceride
      levels were 34% of the levels in the vehicle group. Furthermore, treatment with
      teneligliptin (60mg/kg) reduced plasma levels of insulin to 40% and increased the
      glucose infusion rate to 39%, as measured in the euglycemic clamp study,
      indicating its beneficial effect on insulin resistance. We showed for the first
      time that the DPP-4 inhibitor prevents obesity and obesity-related manifestations
      with increased energy expenditure. Our findings suggest the potential utility of
      teneligliptin for the treatment of a broad spectrum of metabolic disorders
      related to obesity beyond glycemic control. 

PMID- 24309218
TI  - Immediate postabortion access to IUDs, implants and DMPA reduces repeat pregnancy
      within 1 year in a New York City practice.
AB  - OBJECTIVE: The objective was to evaluate whether having intrauterine devices
      (IUDs), contraceptive implants and injections immediately available to women
      undergoing abortion, compared to requiring an additional visit for these methods,
      leads to fewer pregnancies and fewer abortions in the following 12 months.
      METHODS: We conducted a historical cohort study using health records of Medicaid
      insured women obtaining a first-trimester surgical abortion within a single
      practice in New York City. Women in Cohort 1 (2007-2008) needed an additional
      visit to initiate the IUD or injection. Women in Cohort 2 (2008-2009) were able
      to initiate these contraceptives and implants during the abortion visit. Women in
      both cohorts received these methods without additional cost, and all could
      receive a pill, patch or ring prescription. We compared the proportions of each
      cohort who experienced a pregnancy that began in the 12 months following the
      index abortion and also evaluated the outcomes of those pregnancies. RESULTS:
      Cohorts 1 and 2 consisted of 407 and 405 women, respectively. The proportions
      with pregnancy beginning over the following 12 months were substantially greater
      in Cohort 1 than Cohort 2 (27.3% versus 15.3%, p<.001). Women in Cohort 1 then
      underwent both more additional abortions (17.2% versus 9.9%, p=.003) and more
      births (7.9% versus 3.7%, p=.02). The proportion of women in Cohort 1 who
      initiated IUDs and implants within 12 months was smaller than in Cohort 2 (11%
      versus 46%, p<.001). CONCLUSIONS: Among women insured by Medicaid, offering
      immediate comprehensive contraceptive access--including IUDs and implants--on the
      same day as an induced abortion, compared to requiring an additional visit,
      increased uptake of IUDs and implants and decreased repeat pregnancies in the
      next 12 months and abortions.

PMID- 24309219
TI  - Intramuscular ketorolac versus oral ibuprofen for pain relief in first-trimester
      surgical abortion: a randomized clinical trial.
AB  - OBJECTIVE: Oral nonsteroidal antiinflammatory medications (NSAIDs) have been
      shown to reduce pain with first-trimester surgical abortion compared to placebo,
      but it is unclear if one NSAID is better than another. Some providers administer
      intramuscular ketorolac, though data regarding its efficacy in abortion are
      limited. This study was designed to compare oral ibuprofen to intramuscular
      ketorolac for pain management during first-trimester surgical abortion. STUDY
      DESIGN: This was a randomized, double-blind, controlled trial. Women undergoing
      first-trimester surgical abortion with local anesthesia were randomized to
      preprocedural oral ibuprofen, 800 mg given 60-90 min preprocedure, or
      intramuscular ketorolac, 60 mg given 30-60 min preprocedure. The primary outcome
      was pain with uterine aspiration on a 21-point, 0-100, numerical rating scale.
      Secondary outcomes included pain with cervical dilation, postoperative pain and
      patient satisfaction. RESULTS: Ninety-four women were enrolled; 47 were
      randomized to ibuprofen and 47 to ketorolac. The groups did not differ with
      regards to demographics, reproductive history or Depression Anxiety Stress Scale
      scores. Mean pain scores for suction curettage did not differ between groups
      (52.3 vs. 56.2, p=.53). There was also no difference in pain with cervical
      dilation (41.6 vs. 45.4, p=0.48) or postoperative pain (22.3 vs. 15.0 p=.076),
      though patients in the ketorolac group experienced significantly greater arm pain
      than those who received a placebo injection (30.4 vs. 15.6, p<.001). Satisfaction
      with pain control did not differ significantly by group. CONCLUSIONS:
      Intramuscular ketorolac does not offer superior pain control compared to oral
      ibuprofen for first-trimester surgical abortion. IMPLICATIONS: Intramuscular
      ketorolac does not offer superior pain control over oral ibuprofen during first
      trimester surgical abortion, is more expensive and causes patients significant
      arm discomfort. Its use should therefore be reserved for patients who cannot
      tolerate oral NSAIDs.

PMID- 24309220
TI  - The IUB, a newly invented IUD: a brief report.
AB  - OBJECTIVE: To evaluate the initial safety and effectiveness of the intrauterine
      ball (IUB), a copper intrauterine device that, upon insertion in the uterus,
      takes a three-dimensional spherical form. STUDY DESIGN: Fifteen women were
      followed for 1 year, with follow-up visits at 1, 3, 6, 9 and 12 months. RESULTS:
      The physician reported that all devices were very easy to insert. One subject
      discontinued before the 6-month visit (at 119 days after insertion) for a reason
      not related to the device. There were no perforations, expulsions, malpositions
      or complications, or pregnancies. CONCLUSION: No safety or efficacy concerns were
      raised. IMPLICATIONS: Due to its form and deployment process the IUB is expected
      to ease insertion and reduce perforation, malposition and expulsion rates and may
      also reduce dysmenorrhea and menorrhagia.

PMID- 24309221
TI  - Multi-agent model of hepatitis C virus infection.
AB  - OBJECTIVES: The objective of this study is to design a method for modeling
      hepatitis C virus (HCV) infection using multi-agent simulation and to verify it
      in practice. METHODS AND MATERIALS: In this paper, first, the modeling of HCV
      infection using a multi-agent system is compared with the most commonly used
      model type, which is based on differential equations. Then, the implementation
      and results of the model using a multi-agent simulation is presented. To find the
      values of the parameters used in the model, a method using inverted simulation
      flow and genetic algorithm is proposed. All of the data regarding HCV infection
      are taken from the paper describing the model based on the differential equation
      to which the proposed method is compared. RESULTS: Important advantages of the
      proposed method are noted and demonstrated: these include flexibility, clarity,
      re-usability and the possibility to model more complex dependencies. Then, the
      simulation framework that uses the proposed approach is successfully implemented
      in C++ and is verified by comparing it to the approach based on differential
      equations. The verification proves that an objective function that performs the
      best is the function that minimizes the maximal differences in the data. Finally,
      an analysis of one of the already known models is performed, and it is proved
      that it incorrectly models a decay in the hepatocytes number by 40%. CONCLUSIONS:
      The proposed method has many advantages in comparison to the currently used model
      types and can be used successfully for analyzing HCV infection. With almost no
      modifications, it can also be used for other types of viral infections.

PMID- 24309222
TI  - It begins with the right supervisor: importance of mentorship and clinician
      investigator trainee satisfaction levels in Canada.
AB  - PURPOSE: Clinician Investigator Trainee Association of Canada/ Association des
      cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) represents the
      interests of clinician-investigator (CI) trainees across Canada. To better
      advocate for the successful training of CI trainees in Canada, CITAC/ACCFC
      conducted a survey to assess satisfaction with their training and to find what
      factors were most associated with satisfaction level. METHODS: A nominal scale
      based psychometric survey was conducted online in 2009 on CI trainees in Canada
      (including MD/MSc, MD/PhD, or CIP/SSP). One hundred fifteen out of a target
      population of approximately 350-400 responded. Survey respondents were asked to
      rate their level of satisfaction in four areas: 1) quality of training, 2)
      financial support, 3) mentorship satisfaction and 4) program structure. Ratings
      in these four areas were also combined to produce a measure of overall
      satisfaction. RESULTS: At least half of the respondents were 'completely
      satisfied' in each of the four categories other than mentorship. While 98% of
      respondents considered mentorship as important to their success, 62% expressed
      some level of dissatisfaction with the level of mentorship received. Moreover,
      increased levels of mentorship were strongly associated with increased levels of
      overall satisfaction. CONCLUSION: The discrepancy between CI trainees' perceived
      importance of mentorship and the level of satisfaction in mentorship received
      reveals a strategic area where CI training should be improved. Recognizing that
      good mentorship in a CI training program often begins with one's research
      supervisor, the CITAC/ACCFC has compiled six specific recommendations for finding
      a good supervisor.

PMID- 24309223
TI  - Obstructive sleep apnea is prevalent in patients with pulmonary embolism.
AB  - PURPOSE: Obstructive sleep apnea (OSA) syndrome causes systemic consequences due
      to hypoxia and endothelial dysfunction. The purpose of this study was to
      investigate whether OSA is more common in subjects with pulmonary embolism (PE).
      METHODS: This prospective study was conducted between November 2009 and December
      2010 in the Department of Pulmonary Medicine of Gaziantep University. Twenty
      eight patients with PE were included in the study group along with forty-five
      subjects with OSA as the control group. The control group was selected from among
      subjects who were referred to the sleep clinic. Full night polysomnography was
      performed for each subject. RESULTS: Mean apnea-hypopnea index (AHI) was found to
      be higher in the PE group compared with the control group (p=0.010). Severe OSA
      was detected in 21.4% of the PE group but in no controls (p=0.015). Sleep stage 2
      was longer in control group whereas stage 1 and rapid eye movement (REM) sleep
      was longer in the PE group. Snoring and excessive daytime sleepiness were more
      common in the control group compared with the study group. AHI severity and
      thrombus localization were not significantly different between the groups
      (p=0.350). CONCLUSION: Our study findings suggest that OSA is more prevalent and
      severe in subjects with PE compared with control subjects. The clinical
      significance of less prevalent excessive daytime sleepiness and snoring in
      subjects with PE should be evaluated in further studies.

PMID- 24309224
TI  - Clinical significance of leukotriene b4 and extracellular matrix
      metalloproteinase inducer in acute coronary syndrome.
AB  - PURPOSE: Leukotriene B4 (LTB4) and extracellular matrix metalloproteinase
      (EMMPRIN) have been suggested as modulators of atherosclerotic plaque
      instability. This study sought to evaluate the potential diagnostic implication
      of LTB4 and EMMPRIN in patients with acute coronary syndrome (ACS). METHODS:
      Patients (n=153) who underwent coronary angiography, including 105 patients
      diagnosed with ACS, were divided into four groups: stable angina pectoris (SAP,
      n=19), unstable angina pectoris (UAP, n=39), acute myocardial infarction (AMI,
      n=66) and control (with normal coronary angiography, n=29). EMMPRIN expression in
      peripheral blood mononuclear cells was determined by flow cytometry and serum
      LTB4 levels were measured by ELISA. To examine whether LTB4 can regulate the
      expression of EMMPRIN and matrix metalloproteinases (MMPs) in macrophages,
      differentiated THP-1 macrophages were stimulated with different concentrations of
      LTB4 (10-10-10-7mmol/L). Expression of EMMPRIN was evaluated by Western blotting.
      MMP-9 mRNA expression and enzymatic activity were determined by RT-PCR and SDS
      PAGE gelatin zymography. RESULT: Serum LTB4 concentration was significantly
      higher in AMI and UAP groups, compared with control and SAP groups (p < 0.01).
      Subgroups analysis showed that LTB4 was significantly higher in the AMI < 24h
      group, compared with the AMI > 24h group. Expression of EMMPRIN on circulating
      monocytes was significantly higher in patients with UAP and AMI (> 24h), compared
      with control, SAP and AMI (< 24h) groups (p < 0.05). In vitro study showed LTB4
      up-regulated the expression of EMMPRIN, as well as the expression and activity of
      MMP-9, in cultured THP-1-derived macrophages (p < 0.05). CONCLUSION: LTB4 and
      EMMPRIN are associated with the pathogenesis of ACS and may be potential
      biomarkers for patients with ACS.

PMID- 24309225
TI  - Warning letters to sponsor-investigators at academic health centres - the
      regulatory "canaries in a coal mine".
AB  - PURPOSE: This study highlights Warning Letter (WL) findings issued to sponsor
      investigators (S-Is) by the Food and Drug Administration (FDA). METHODS: The
      online index of WLs issued from October 1, 2007 through September 30, 2012 was
      reviewed [1]. Through a manual screening process, letters were evaluated if
      specifically issued to 'clinical investigators', 'sponsors' or 'sponsor
      investigators'. A particular focus was given to S-Is at Academic Health Centres
      (AHCs). Each letter was scored for the presence of violations in 40 general
      regulatory categories. RESULTS: A review of FDA WLs issued over a five-year
      period (FDA Fiscal Years 2008-2012) revealed that WLs to S-Is represent half of
      the WLs issued to all sponsors (16 of 32 letters). A review of these letters
      indicates that S-Is are not aware of, or simply do not meet, their regulatory
      responsibilities as either investigators or sponsors. In comparing total sponsor
      letters to those of S-Is, the most cited violation was the same: a lack of
      monitoring. A review of publicly available inspection data indicates that these
      16 letters merely represent the tip of the iceberg. CONCLUSION: This review of
      the WL database reveals the potential for serious regulatory violations among S
      Is at AHCs. Recent translational funding initiatives may serve to increase the
      number of S-Is, especially among Academic Health Centres (AHCs) [2]; thus, AHCs
      must become aware of this S-I role and work to support investigators who assume
      both roles in the course of their research.

PMID- 24309226
TI  - Prognostic significance of body mass index in breast cancer patients with hormone
      receptor-positive tumours after curative surgery.
AB  - PURPOSE: Obesity has been recognized as a significant risk factor for
      postmenopausal breast cancer. The aim of this study is to investigate the
      prognostic significance of body mass index (BMI) in hormone receptor-positive,
      operable breast cancer. METHODS: In this retrospective cohort study, 1,192
      consecutive patients with curative resection of primary breast cancer were
      enrolled. Patients were assigned to two groups according to BMI: normal or
      underweight (BMI < 23.0 kg/m2) and overweight or obese (BMI >= 23.0 kg/m2).
      Associations among BMI and clinicopathological characteristics and prognosis of
      patients were assessed. RESULTS: A high BMI was significantly (P < 0.01)
      correlated with age, nodal stage, ALNR, ER positivity, PR positivity and
      menopausal status at diagnosis. Univariate analysis revealed that BMI, pathologic
      T stage, nodal stage, axillary lymph node ratio (ALNR) and adjuvant radiotherapy
      history were significantly (P < 0.05) associated with disease-free survival and
      overall survival, irrespective of tumour hormone receptor status. Multivariate
      analysis revealed BMI as an independent prognostic factor in all cases and in
      hormone receptor-positive cases. CONCLUSION: A high BMI (>= 23.0 kg/m2) is
      independently associated with poor prognosis in hormone receptor-positive breast
      cancer.

PMID- 24309227
TI  - Association of serum YKL-40 levels with the presence and severity of coronary
      artery disease in patients with obstructive sleep apnea syndrome.
AB  - PURPOSE: Current evidence supports a robust association between obstructive sleep
      apnea syndrome (OSAS) and the risk of coronary artery disease (CAD). YKL-40, a 40
      kDa heparin- and chitin-binding glycoprotein, is found to be associated with the
      presence of CAD. This study aims to examine the association of serum levels of
      YKL-40 with the presence and severity of CAD in patients with OSAS. METHODS: A
      total of 246 patients with OSAS who underwent coronary angiography for the
      evaluation of CAD (134 patients with CAD and 112 patients without CAD) were
      enrolled in this study. The severity of CAD was assessed using the coronary
      atherosclerosis index (CAI). Serum levels of YKL-40 were determined using enzyme
      linked immunosorbent assay. RESULTS: Serum YKL-40 levels were significantly
      higher in OSAS patients with CAD compared with those without CAD. Multivariable
      logistic regression analysis revealed that serum YKL-40 levels were an
      independent determinant of the presence of CAD in patients with OSAS. In
      addition, Spearman correlation analysis showed that serum YKL-40 levels were
      positively correlated with CAI in OSAS patients with CAD. Patients with statin
      treatment showed significantly lower levels of serum YKL-40 compared with those
      without. CONCLUSIONS: Elevated levels of serum YKL-40 are associated with the
      presence and severity of CAD in patients with OSAS.

PMID- 24309228
TI  - Human hair cortisol analysis: comparison of the internationally-reported ELISA
      methods.
AB  - PURPOSE: Recently, hair cortisol has become a topic of global interest as a
      biomarker of chronic stress. Different research groups have been using different
      methods for extraction and analysis, making it difficult to compare results
      across studies. A critical examination of the reported analytical methods is
      important to facilitate standardization and allow for a uniform interpretation.
      METHODS: This study qualitatively compared four published procedures from
      laboratories in Germany, the Netherlands, USA and Canada. Multiple aspects of
      their procedures were compared. RESULTS: A major difference among the
      laboratories was the ELISA kit used: the Canadian laboratory used the kit from
      ALPCO Diagnostics (Salem, MA, USA), the American laboratory used the kit from DRG
      International (Springfield, NJ, USA), the German laboratory used the kit from DRG
      Instruments GmbH (Marburg, Germany), or IBL (Hamburg, Germany), and the Dutch
      used the kit from Salimetrics (Suffolk, UK). In addition, there are noted
      differences in hair mass used as well as washing and extraction procedures. The
      range of hair cortisol levels determined in healthy volunteers by the four groups
      was within 2.3-fold: Koren, 46.1 pg/mg; Van Rossum, 29.72 pg/mg; Kirschbaum, 20
      pg/mg and Laudenslager ~ 27 pg/mg. CONCLUSIONS: The relative similarities in hair
      cortisol values in volunteers among the four laboratories should facilitate a
      quality assurance exchange program, as a necessary step toward clinical use of
      this novel test.

PMID- 24309229
TI  - Preface to the special edition of Clin Chem Acta: utilization management in the
      clinical laboratory.

PMID- 24309230
TI  - Biodecolorization of a food azo dye by the deep sea Dermacoccus abyssi MT1.1(T)
      strain from the Mariana Trench.
AB  - This study reports the characterization of the ability of Dermacoccus spp.
      isolated from the deepest point of the world's oceans for azo dye decolorization.
      A detailed investigation of Dermacoccus abyssi MT1.1(T) with respect to the
      azoreductase activity and enzymatic mechanism as well as the potential role of
      the bacterial strain for biocleaning of industrial dye baths is reported. Resting
      cells with oxygen-insensitive azoreductase resulted in the rapid decolorization
      of the polysulfonated dye Brilliant Black BN (BBN) which is a common food
      colorant. The highest specific decolorization rate (vs) was found at 50  degrees
      C with a moderately thermal tolerance for over 1 h. Kinetic analysis showed the
      high rates and strong affinity of the enzymatic system for the dye with a Vmax =
      137 mg/g cell/h and a Km = 19 mg/L. The degradation of BBN produces an initial
      orange intermediate, 8-amino-5-((4-sulfonatophenyl)diazenyl)naphthalene-2
      sulfonic acid, identified by mass spectrometry which is later converted to 4
      aminobenzene sulfonic acid. Nearly 80% of the maximum vs is possible achieved in
      resting cell treatment with the salinity increased up to 5.0% NaCl in reaction
      media. Therefore, this bacterial system has potential for dye decolorization
      bioprocesses occurring at high temperature and salt concentrations e.g. for
      cleaning dye-containing saline wastewaters. 

PMID- 24309231
TI  - Application of analytical hierarchy process for effective selection of
      agricultural best management practices.
AB  - In this study an analytical hierarchy process (AHP) was used for ranking best
      management practices (BMPs) in the Saginaw River Watershed based on
      environmental, economic and social factors. Three spatial targeting methods were
      used for placement of BMPs on critical source areas (CSAs). The environment
      factors include sediment, total nitrogen, and total phosphorus reductions at the
      subbasin level and the watershed outlet. Economic factors were based on total BMP
      cost, including installation, maintenance, and opportunity costs. Social factors
      were divided into three favorability rankings (most favorable, moderately
      favorable, and least favorable) based on area allocated to each BMP. Equal
      weights (1/3) were considered for the three main factors while calculating the
      BMP rank by AHP. In this study three scenarios were compared. A comprehensive
      approach in which environmental, economic, and social aspects are simultaneously
      considered (Scenario 1) versus more traditional approaches in which both
      environmental and economic aspects were considered (Scenario 2) or only
      environmental aspects (sediment, TN, and TP) were considered (Scenario 3). In
      Scenario 1, only stripcropping (moderately favorable) was selected on all CSAs at
      the subbasin level, whereas stripcropping (49-69% of CSAs) and residue management
      (most favorable, 31-51% of CSAs) were selected by AHP based on the watershed
      outlet and three spatial targeting methods. In Scenario 2, native grass was
      eliminated by moderately preferable BMPs (stripcropping) both at the subbasin and
      watershed outlet levels due the lower BMP implementations cost compared to native
      grass. Finally, in Scenario 3, at subbasin level, the least socially preferable
      BMP (native grass) was selected in 100% of CSAs due to greater pollution
      reduction capacity compared to other BMPs. At watershed level, nearly 50% the
      CSAs selected stripcropping, and the remaining 50% of CSAs selected native grass
      and residue management equally. 

PMID- 24309232
TI  - Sorptive removal of arsenate using termite mound.
AB  - Long-term consumption of arsenic results in severe and permanent health damages.
      The aim of the study was to investigate arsenate (As(V)) sorption capacity of
      termite mound (TM), containing mainly silicon, aluminum, iron and titanium
      oxides, under batch adsorption setup. The pattern of As(V) removal with varying
      contact time, solution pH, adsorbent dose, As(V) concentration and competing
      anions was investigated. Dissolution of the adsorbent was insignificant under the
      equilibrium conditions. Equilibrium was achieved within 40 min of agitation time.
      Kinetic data of As(V) adsorption followed well the pseudo-second order equation
      (R(2) > 0.99). High As(V) removal efficiency (~ 99%) was observed over a pH range
      ~ 3-~ 10, which is of great importance in the practical application. The
      Freundlich and Dubinin-Radushkevich isotherms well described (R(2) > 0.99, chi(2)
      ~ 0.05) the equilibrium As(V) adsorption, giving a coefficient of adsorption 1.48
      mg(1-1/n)L(1/n)/g and a saturation capacity 13.50 mg/g respectively. The obtained
      value of mean sorption energy (EDR = 13.32 kJ/mol) suggested the chemisorption
      mechanism of As(V) adsorption on TM. The removal of As(V) was significantly
      decreased in the presence of phosphate ions. The As(V) loaded adsorbent was
      successfully regenerated using NaOH solution with insignificant loss of metals.
      Therefore, the results of the study demonstrated that TM could be considered as a
      promising adsorbent for the treatment of As(V) in drinking water. 

PMID- 24309233
TI  - Resumption of work after acute coronary syndrome or coronary artery bypass graft
      surgery.
AB  - BACKGROUND: Return to work is an important indicator of recovery after acute
      cardiac events. This study aimed to determine rates of work resumption and
      identify predictors of non-return to work and delayed resumption of work.
      METHODS: 401 currently employed patients consecutively admitted after acute
      coronary syndrome or to undergo coronary artery bypass graft surgery were
      recruited. Patient characteristics, perceptions and occupational outcomes were
      investigated via interviews and self-report questionnaires. RESULTS: Twenty-three
      patients were lost to follow-up. Of the 378 completers, 343 (90.7%) patients
      resumed work, while 35 (9.3%) did not. By four months, 309 (91.1%) patients had
      returned to work. At 12 months, 302 (79.9%) of the 378 patients were employed, 32
      (8.5%) unemployed and 20 (5.3%) retired. The employment status of 24 (6.3%)
      patients was unknown. Non-return to work was significantly more likely if
      patients were not intending to return to work or were uncertain, had a negative
      perception of health, had a comorbidity other than diabetes and reported
      financial stress. Significant predictors of delayed return to work were cardiac
      rehabilitation attendance, longer hospital stay, past angina, having a manual
      job, physically active work, job dissatisfaction, no confidante and depression.
      CONCLUSIONS: Patients at risk of poor occupational outcomes can be identified
      early. Strategies to improve vocational rehabilitation require further
      investigation.

PMID- 24309234
TI  - Cordyceps sinensis polysaccharide CPS-2 protects human mesangial cells from PDGF
      BB-induced proliferation through the PDGF/ERK and TGF-beta1/Smad pathways.
AB  - CPS-2, a Cordyceps sinensis polysaccharide, has been demonstrated to have
      significant therapeutic activity against chronic renal failure. However, little
      is known about the underlying molecular mechanism. In this study, we found that
      CPS-2 could inhibit PDGF-BB-induced human mesangial cells (HMCs) proliferation in
      a dose-dependent manner. In addition, CPS-2 notably suppressed the expression of
      alpha-SMA, PDGF receptor-beta (PDGFRbeta), TGF-beta1, and Smad 3 in PDGF-BB
      treated HMCs. Furthermore, PDGF-BB-stimulated ERK activation was significantly
      inhibited by CPS-2, and this inhibitory effect was synergistically potentiated by
      U0126. CPS-2 could prevent the PDGFRbeta promoter activity induced by PDGF-BB,
      and return expression of PDGFRbeta, TGF-beta1, and TGFbetaRI to normal levels
      while cells were under PDGFRbeta and ERK silencing conditions and transfected
      with DN-ERK. Taken together, these findings demonstrated that CPS-2 reduces PDGF
      BB-induced cell proliferation through the PDGF/ERK and TGF-beta1/Smad pathways,
      and it may have bi-directional regulatory effects on the PDGF/ERK cellular
      signaling pathway. 

PMID- 24309235
TI  - [Should we perform intra-operative endometrial biopsy during pelvic
      reconstructive surgery with uterine preservation?].
AB  - OBJECTIVE: To evaluate the interest of systematic endometrial biopsy at the time
      of vaginal reconstructive surgery with uterine preservation. METHODS: We
      performed a retrospective monocentric study on all women who had vaginal
      reconstructive surgery with uterine preservation from 2005 to 2012. All following
      parameters have been studied: baseline characteristics (age, parity, BMI,
      hormonal status, medical history), prolapse stage using the POP-Q, preoperative
      pelvic ultrasound (endometrial thickness), and type of surgery. Women with
      previous hysterectomy were excluded. RESULTS: Four hundred and fourteen patients
      were operated during this period, and 268 have uterine preservation (64.7%).
      Baseline characteristics were mean age 64.7+/-10.7 (39 to 92), mean parity 2.6+/
      1.5, mean BMI 25.5+/-4.2, menopause 238 (88.8%), HRT 32 (12%), previous breast
      cancer 16 (6%), diabetes mellitus 31 (11.6%), and hypertension 87 (32.5%).
      Prolapse were at stage II in 127 (47.3%), stage III in 99 (36.9%) and stage IV in
      17 (6.3%). Preoperative pelvic ultrasound has been done in 255 patients (95.2%),
      and mean endometrial thickness was 5.1mm (range 1.6-16). Overall, 152 intra
      operative endometrial biopsies were assessable (56.7%). In 24 cases (15.8%),
      samples were too small to be interpretable. Finally, the 128 interpretable
      biopsies (82.2%) have shown one carcinoma (0.8%), four hyperplasia (3.2%), two
      endometrial polyps (1.6%), and 121 normal endometria (94.5%). The only cancer was
      discovered on a 77 year old patient, with a history of previous breast cancer,
      and with a preoperative endometrial thickness of 7 mm. No patient with normal
      preoperative ultrasound endometrial screening had abnormal endometrial biopsy.
      CONCLUSION: Vaginal reconstructive surgery with uterine preservation implicates a
      preoperative endometrial evaluation by ultrasound. Intra-operative endometrial
      biopsy does not seem to be justified.

PMID- 24309236
TI  - A review of cellular therapies for chronic lymphocytic leukemia.

PMID- 24309237
TI  - Intimate relationship status variations in violence against women: urban,
      suburban, and rural differences.
AB  - Woman abuse varies across intimate relationship categories (e.g., marriage,
      divorce, separation). However, it is unclear whether relationship status
      variations in violence against women differ across urban, suburban, and rural
      areas. We test the hypothesis that rural females, regardless of their intimate
      partner relationship status, are at higher risk of intimate violence than their
      urban and suburban counterparts. Results indicate that marital status is an
      important aspect of the relationship between intimate victimization and
      geographic area and that rural divorced and separated females are victimized at
      rates exceeding their urban counterparts. 

PMID- 24309238
TI  - Outcomes of vagal nerve stimulation in a pediatric population: a single center
      experience.
AB  - OBJECTIVE: To evaluate the efficacy of vagus nerve stimulation (VNS) in pediatric
      patients with medically refractory epilepsy. METHOD: We reviewed the medical
      records of 252 consecutive patients who underwent VNS implantation at a single
      center over a 5-year period. Patients with complete 6- and 12-month follow-up
      data were included. Analysis was also done across various subgroups including
      gender, age at implantation, seizure type, abnormal MRI findings pre
      implantation, number of medications at baseline, history of SE, and duration of
      epilepsy. RESULTS: Complete follow-up data were available for 69 patients. Median
      seizure reduction for these patients was 50% (Q1: 0%; Q3: 73%) at 6 months and
      40% (Q1: -25%; Q3: 75%) at 12 months. When stratified by baseline seizure
      frequency, there was a significant reduction from baseline of 61% at 6 months and
      69% at 12 months for patients in the high-baseline frequency group. There were no
      significant reductions at month 6 or 12 months for the lower-baseline frequency
      group. Adverse events were reported in 40.6% (28 out of 69 patients). Six
      patients had the VNS removed for reasons including lack of efficacy and side
      effects and were excluded from the study group. CONCLUSION: VNS provides
      significant seizure reduction, in particular in pediatric patients with a higher
      baseline seizure frequency.

PMID- 24309239
TI  - Transient parkinsonism following mycoplasma pneumoniae infection with normal
      brain magnetic resonance imaging (MRI).
AB  - Parkinsonism caused by infection is uncommon in children. We report 2 previously
      healthy children with acute self-limiting parkinsonism following Mycoplasma
      pneumoniae infection, with normal brain magnetic resonance imaging (MRI). Our
      case report expands the phenotype of parkinsonism associated with M. pneumoniae
      infection. We recommend that children with acute parkinsonism preceded by a
      period of febrile illness, even with a normal brain MRI, should be investigated
      for M. pneumoniae infection.

PMID- 24309240
TI  - Reproducibility of detecting silent cerebral infarcts in pediatric sickle cell
      anemia.
AB  - Detecting silent cerebral infarcts on magnetic resonance images (MRIs) in
      children with sickle cell anemia is challenging, yet reproducibility of readings
      has not been examined in this population. We evaluated consensus rating, inter-,
      and intra-grader agreement associated with detecting silent cerebral infarct on
      screening MRI in the Silent Infarct Transfusion Trial. Three neuroradiologists
      provided consensus decisions for 1073 MRIs. A random sample of 53 scans was
      reanalyzed in blinded fashion. Agreement between first and second consensus
      ratings was substantial (kappa = 0.70, P < .0001), as was overall intergrader
      agreement (kappa = 0.76, P < .0001). In the test-retest sample, intragrader
      agreement ranged from kappa of 0.57 to 0.76. Consensus decisions were more
      concordant when MRIs contained more than one larger lesions. Routine use of MRI
      to screen for silent cerebral infarcts in the research setting is reproducible in
      sickle cell anemia and agreement among neuroradiologists is sufficient. 

PMID- 24309241
TI  - Severe respiratory dysrhythmia in Rett syndrome treated with topiramate.
AB  - Rett syndrome is a neurodevelopmental disorder that manifests itself early in
      childhood, progresses with the evolution of characteristic clinical signs and
      symptoms and is confirmed by mutation in the methyl-CpG-binding protein 2 gene.
      Seizures are present in a majority of Rett patients. Respiratory dysrhythmia in
      the awake state is present in two-thirds of patients, leading in some cases to
      severe nonepileptic paroxysmal events. There are no optimal treatment
      recommendations thus far. The aim of this case study is to present the electro
      clinical correlation of severe respiratory dysrhythmia mimicking seizures in 2
      Rett patients and effective treatment with topiramate. 

PMID- 24309242
TI  - Predictors of response to vagus nerve stimulation in childhood-onset medically
      refractory epilepsy.
AB  - This study explored predictors of response to vagus nerve stimulation in
      childhood-onset epilepsy. This retrospective chart review included all patients
      with new vagus nerve stimulator insertion between January 1, 2006, and December
      31, 2011. Primary outcome was change in seizure frequency classified on the
      International League Against Epilepsy scale. Overall, 67.4% (95% confidence
      limits 53.3%-81.6%) of the patients had outcome of class 4 or better, and 4
      patients (9.3%, 95% confidence interval 0.5%-18.1%) achieved complete seizure
      freedom (mean follow-up 3.5 y). Absence of magnetic resonance imaging (MRI)
      lesion (odds ratio 6.068, 95% confidence interval 1.214-30.329, P = .028) and
      duration of epilepsy before implantation (odds ratio 1.291, 95% confidence
      interval 1.015-1.642, P = .038) were found to be statistically significant
      predictors of good outcome and provided a sufficient fit to the data (area under
      the receiver operating characteristic curve .80, Hosmer-Lemeshow goodness of fit
      P = .92). This study provides preliminary evidence that nonlesional patients are
      significantly more likely to have better outcome with vagus nerve stimulation. 

PMID- 24309243
TI  - Linear growth of children on a ketogenic diet: does the protein-to-energy ratio
      matter?
AB  - Ketogenic diet is a structured effective treatment for children with intractable
      epilepsy. Several reports have indicated poor linear growth in children on the
      diet but the mechanism of poor growth has not been elucidated. We aimed to
      explore whether the protein to energy ratio plays a role in linear growth of
      children on ketogenic diet. Data regarding growth and nutrition were,
      retrospectively, collected from the clinical histories of 35 children who were
      treated with ketogenic diet for at least 6 months between 2002 and 2010. Patients
      were stratified into groups according to periods of satisfactory or poor linear
      growth. Poor linear growth was associated with protein or caloric intake of <80%
      recommended daily intake, and with a protein-to-energy ratio consistently <=1.4 g
      protein/100 kcal even when protein and caloric intakes were adequate. We
      recommend a protein-to-energy ratio of 1.5 g protein/100 kcal be prescribed to
      prevent growth retardation. 

PMID- 24309244
TI  - Legionella pneumophila and Pneumocystis jirovecii coinfection in an infant
      treated with adrenocorticotropic hormone for infantile spasm: case report and
      literature review.
AB  - We describe an 8-month-old infant with infantile spasms treated with
      adrenocorticotropic hormone (ACTH) who presented with fatal Legionella
      pneumophila and Pneumocystis jirovecii infection. Emphasis is placed on the
      ensuing immunosuppression and infectious sequelae of ACTH therapy. Given that
      ACTH therapy may increase the risk of fatal infection, patients undergoing such
      treatment should be closely monitored, with particular attention paid to the
      functioning of the immune system. 

PMID- 24309245
TI  - Benign and periodic movement disorders in 2 children with Down syndrome.
AB  - Children with Down syndrome show hypotonia and ligamentous laxity that are
      associated with motor development delay. Neurologic disorders are common in
      children with Down syndrome; however, in literature the presence of periodic
      movement disorders has not yet been described. We report 2 different types of
      periodic movement disorders in 2 infants with Down syndrome. In the first case,
      we described an 8-month-old girl with involuntary head nodding and absence of any
      other neurologic or ophthalmologic abnormalities. In the second case, we
      described a 6-month-old boy with abnormal but painless head rotation and
      inclination, alternating from side to side. Episodes of head tilting were often
      associated with a state of general uneasiness. Neurologic examination between
      attacks was normal. The aim of this paper is to provide practical information on
      recognition and management of movement disorders in Down syndrome. 

PMID- 24309246
TI  - Beyond irrelevant actions: understanding the role of intentionality in children's
      imitation of relevant actions.
AB  - The current research examines how 3- to 5-year-old children use intentionality to
      understand the causal structure of objects in an observational learning context.
      Two studies are presented in which the intentionality of relevant actions was
      manipulated during toy retrieval demonstrations and contrasted with whether these
      actions remained relevant or were rendered irrelevant for the child's turn. Of
      interest were whether children would imitate the first action when it was
      demonstrated intentionally but rendered irrelevant and how they would approach
      the first action when it was demonstrated accidentally and remained relevant.
      Findings revealed that children did not align themselves with the demonstrator's
      intentions in Study 1, when apparatuses were transparent, but did follow the
      demonstrator's intentions in Study 2, when apparatuses were opaque. This suggests
      that when causality of relevant actions is unambiguous, children use their own
      causal reasoning abilities, but ambiguous causal structure prompts children to
      defer to a demonstrator. It is suggested that opaque relevant actions may
      represent a real life parallel to irrelevant actions, the imitation of which is
      motivated by inherent ambiguity. 

PMID- 24309247
TI  - Children's neural response to contrast-negated faces is species specific.
AB  - Face recognition abilities develop dramatically during the first year of life,
      but comparatively little is known about the nature of face-specific perceptual
      development during early childhood. Face-specific effects of image appearance on
      recognition, including face inversion and contrast negation, are a useful means
      of understanding the functional properties of face perception developmentally.
      Here, we examined the generality of the impact of contrast negation on face
      perception during early childhood using event-related potentials (ERPs).
      Specifically, we recorded continuous electroencephalography (EEG) while adult
      participants and children between 4 and 6 years of age viewed human and non-human
      primate faces presented in either positive or negative contrast. We examined both
      the P100 and N170 components to determine whether or not sensitivity to contrast
      polarity was evident in face-sensitive components during early childhood and also
      whether or not that sensitivity was specific to species category. We found
      evidence of a species-specific effect of contrast negation at the N170,
      suggesting that by early childhood some aspects of face-specific processing have
      been restricted to a relatively narrow class of face stimuli. However, this
      effect is of the opposite sign relative to adults, suggesting that there is
      continued maturation of face-specific processing during childhood.

PMID- 24309248
TI  - Tissue-specific regulation of 3'-nucleotide hydrolysis and nucleolar
      architecture.
AB  - Sulfur is an essential micronutrient involved in diverse cellular functions
      ranging from the control of intracellular redox states to electron transport.
      Eukaryotes incorporate sulfur by metabolizing inorganic sulfate into the
      universal sulfur donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS).
      Sulfotransferases then catalyze the donation of the activated sulfur from PAPS to
      a broad range of acceptors including xenobiotic small molecules and extracellular
      proteoglycans while also generating the byproduct 3'-phosphoadenosine 5'
      phosphate (PAP). In mammals, PAP is regulated by two related 3'-nucleotidases,
      Golgi-resident PAP phosphatase (gPAPP) and cytoplasmic bisphosphate 3'
      nucleotidase 1 (Bpnt1), which hydrolyze PAP to 5'-AMP and whose inactivation
      results in severe physiological defects. Loss of Bpnt1 in mice leads to the
      accumulation of PAP in the liver, aberrant nucleolar architecture, and liver
      failure, all of which can be rescued by genetically repressing PAPS synthesis.
      Yet interestingly, Bpnt1 protein is expressed at high levels in a majority of
      tissues, suggesting that additional tissues might also be affected. To
      investigate this possibility, we closely examined the expression of Bpnt1
      protein, accumulation of PAP, and appearance of dysmorphic nucleoli in wild-type
      and Bpnt1(-/-) mice. Surprisingly, we found that while Bpnt1 protein is widely
      expressed, only the liver, duodenum, and kidneys contain high levels of PAP and
      nucleolar reorganization. We hypothesize that these tissues share commonalities
      such as being highly polarized and situated at the interfaces of fluid reservoirs
      that might enhance their susceptibility to loss of Bpnt1. These studies highlight
      the importance of PAP metabolism in extrahepatic tissues and provide a framework
      for future investigations into the function of Bpnt1 in the kidney and small
      intestine. 

PMID- 24309249
TI  - Balancing plasticity/stability across brain development.
AB  - The potency of the environment to shape brain function changes dramatically
      across the lifespan. Neural circuits exhibit profound plasticity during early
      life and are later stabilized. A focus on the cellular and molecular bases of
      these developmental trajectories has begun to unravel mechanisms, which control
      the onset and closure of such critical periods. Two important concepts have
      emerged from the study of critical periods in the visual cortex: (1) excitatory
      inhibitory circuit balance is a trigger; and (2) molecular "brakes" limit adult
      plasticity. The onset of the critical period is determined by the maturation of
      specific GABA circuits. Targeting these circuits using pharmacological or genetic
      approaches can trigger premature onset or induce a delay. These manipulations are
      so powerful that animals of identical chronological age may be at the peak,
      before, or past their plastic window. Thus, critical period timing per se is
      plastic. Conversely, one of the outcomes of normal development is to stabilize
      the neural networks initially sculpted by experience. Rather than being passively
      lost, the brain's intrinsic potential for plasticity is actively dampened. This
      is demonstrated by the late expression of brake-like factors, which reversibly
      limit excessive circuit rewiring beyond a critical period. Interestingly, many of
      these plasticity regulators are found in the extracellular milieu. Understanding
      why so many regulators exist, how they interact and, ultimately, how to lift them
      in noninvasive ways may hold the key to novel therapies and lifelong learning. 

PMID- 24309250
TI  - Brain plasticity in the developing brain.
AB  - The developing normal brain shows a remarkable capacity for plastic change in
      response to a wide range of experiences including sensory and motor experience,
      psychoactive drugs, parent-child relationships, peer relationships, stress,
      gonadal hormones, intestinal flora, diet, and injury. The effects of injury vary
      with the precise age-at-injury, with the general result being that injury during
      cell migration and neuronal maturation has a poor functional outcome, whereas
      similar injury during synaptogenesis has a far better outcome. A variety of
      factors influence functional outcome including the nature of the behavior in
      question and the age at behavioral assessment as well as pre- and postinjury
      experiences. Here, we review the phases of brain development, how factors
      influence brain, and behavioral development in both the normal and perturbed
      brain, and propose mechanisms that may underlie these effects. 

PMID- 24309253
TI  - What does it take to show that a cognitive training procedure is useful? A
      critical evaluation.
AB  - Individuals substantially improve with training, indicating that a large degree
      of plasticity is retained across ages. In the past 20 years, many studies
      explored the ability to boost cognitive skills (reasoning, linguistic abilities,
      working memory, and attention) by training with other tasks that exploit limited
      cognitive resources. Indeed, individuals with long-term training on challenging
      skills (musicians and action video gamers) show impressive behavior on related
      tasks (linguistic and visual attention, respectively). However, a critical
      evaluation of training studies that last weeks to months shows typically mild
      effects, mainly with respect to control groups that either did not practice or
      practiced with less challenging, rewarding, or exciting conditions. These
      findings suggest that future training studies should evaluate these factors
      carefully and assess whether they mainly impact the testing sessions or actual
      longer-term skills, and whether their impact can be further strengthened. The
      lack of a comprehensive theory of learning that integrates cognitive,
      motivational, and alertness aspects poses a bottleneck to improving current
      training procedures. 

PMID- 24309251
TI  - Cortical plasticity, excitatory-inhibitory balance, and sensory perception.
AB  - Experience shapes the central nervous system throughout life. Structural and
      functional plasticity confers a remarkable ability on the brain, allowing neural
      circuits to adequately adapt to dynamic environments. This process can require
      selective adjustment of many excitatory and inhibitory synapses in an organized
      manner, in such a way as to enhance representations of behaviorally important
      sensory stimuli while preserving overall network excitability. The rules and
      mechanisms that orchestrated these changes across different synapses and
      throughout neuronal ensembles are beginning to be understood. Here, we review the
      evidence connecting synaptic plasticity to functional plasticity and perceptual
      learning, focusing on the roles of various neuromodulatory systems in enabling
      plasticity of adult neural circuits. However, the challenge remains to
      appropriately leverage these systems and forms of plasticity to persistently
      improve perceptual abilities and behavioral performance. 

PMID- 24309254
TI  - Principles of neuroplasticity-based rehabilitation.
AB  - The purpose of this review is to summarize how our perspective about the
      neuroscience of brain plasticity, informed by perceptual, experimental, and
      cognitive psychology, has led to the designs of a new class of therapeutic tools
      developed to drive functionally distorted and damaged brains in corrective
      directions. How does neuroplasticity science inform us about optimal therapeutic
      program designs? How do we apply that science, using modern technology, to drive
      neurological changes that address both the neurobehavioral distortions and the
      resulting behavioral deficits that are expressed in specific neurological and
      psychiatric disorders? By what strategies can we achieve the strongest and most
      complete rehabilitative corrections? These are questions that we have extensively
      explored in our efforts to establish new medical applications of neuroplasticity
      based therapeutics. Here, we summarize the state of this rapidly emerging area of
      translational neuroscience, beginning with an explanation of the scientific
      premises and strategies, then describing their implementation in therapeutic
      software to address two human illnesses: the treatment of social cognition
      deficits in chronic schizophrenia and in autism; and the amelioration of age
      related functional decline using strategies designed to delay the onset of--and
      potentially prevent--Alzheimer's Disease and related causes of dementia in aging.

PMID- 24309255
TI  - Fast ForWord(r): the birth of the neurocognitive training revolution.
AB  - In 1996, I cofounded Scientific Learning Corporation (SLC) with Drs Michael
      Merzenich, William Jenkins, and Steve Miller. I coined the term "Cogniceutical"
      to describe the new type of company we envisioned. SLC was the first company
      cofounded by academic scientists with the mission of building neurocognitive
      interventions. Fast ForWord(r) is the registered trade name of the platform SLC
      built to translate basic neuroplasticity-based training research into clinical
      and educational products. Fast ForWord(r) was the first cognitive
      neurotherapeutic intervention, the first to be individually adaptive in real
      time, the first "brain fitness" program that collected data over the Internet,
      and the first to use computer gaming technologies to change brains and enhance
      human potential. We included lofty goals in our first business plan for SLC.
      These included: using neuroplasticity-based training to improve language,
      literacy, and other academic skills; helping seniors maintain and recover
      function; helping people learn English as a second language; helping patient
      populations with neurological or mental disorders. SLC's first focus became
      improving language and literacy. Mike, Bill, Steve, and I began this journey
      together in 1994 with a laboratory-based research study that included seven
      children. To date, over two million children in 46 countries have used Fast
      ForWord(r) products. On any given school day, approximately 60,000 children log
      in to train on 1 of 10 Fast ForWord Language, Literacy, or Reading programs. We
      did not know at the time that we were creating what became a "disruptive
      innovation." This chapter chronicles this transformational journey. 

PMID- 24309252
TI  - Changes in plasticity across the lifespan: cause of disease and target for
      intervention.
AB  - We conceptualize brain plasticity as an intrinsic property of the nervous system
      enabling rapid adaptation in response to changes in an organism's internal and
      external environment. In prenatal and early postnatal development, plasticity
      allows for the formation of organized nervous system circuitry and the
      establishment of functional networks. As the individual is exposed to various
      sensory stimuli in the environment, brain plasticity allows for functional and
      structural adaptation and underlies learning and memory. We argue that the
      mechanisms of plasticity change over the lifespan with different slopes of change
      in different individuals. These changes play a key role in the clinical phenotype
      of neurodevelopmental disorders like autism and schizophrenia and
      neurodegenerative disorders such as Alzheimer's disease. Altered plasticity not
      only can trigger maladaptive cascades and can be the cause of deficits and
      disability but also offers opportunities for novel therapeutic interventions. In
      this chapter, we discuss the importance of brain plasticity across the lifespan
      and how neuroplasticity-based therapies offer promise for disorders with
      otherwise limited effective treatment. 

PMID- 24309256
TI  - Music training for the development of reading skills.
AB  - The beneficial effects of musical training are not limited to enhancement of
      musical skills, but extend to language skills. Here, we review evidence that
      musical training can enhance reading ability. First, we discuss five subskills
      underlying reading acquisition-phonological awareness, speech-in-noise
      perception, rhythm perception, auditory working memory, and the ability to learn
      sound patterns-and show that each is linked to music experience. We link these
      five subskills through a unifying biological framework, positing that they share
      a reliance on auditory neural synchrony. After laying this theoretical groundwork
      for why musical training might be expected to enhance reading skills, we review
      the results of longitudinal studies providing evidence for a role for musical
      training in enhancing language abilities. Taken as a whole, these findings
      suggest that musical training can provide an effective developmental educational
      strategy for all children, including those with language learning impairments. 

PMID- 24309257
TI  - Mechanisms of plasticity in the developing and adult visual cortex.
AB  - The visual cortex provides powerful evidence for experience-dependent plasticity
      during development, and for stimulus and reinforcement-dependent plasticity in
      adulthood. The synaptic and circuit mechanisms underlying such plasticity are
      being progressively understood. Increasing evidence supports the hypothesis that
      plasticity in both the developing and adult visual cortex is initiated by a
      transient reduction of inhibitory drive, and implemented by persistent changes at
      excitatory synapses. Developmental plasticity may be induced by alterations in
      the balance of activity from the two eyes and is implemented by a cascade of
      signals that lead to feedforward and feedback changes at synapses. Adult
      plasticity is imposed on mature synapses and requires additional neurotransmitter
      dependent mechanisms that alter inhibition and subsequently response gain. 

PMID- 24309258
TI  - Brain mechanisms of plasticity in response to treatments for core deficits in
      autism.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by
      social communication impairments and repetitive behaviors. Although the
      prevalence of ASD is estimated at 1 in 88, understanding of the neural mechanisms
      underlying the disorder is still emerging. Regions including the amygdala,
      superior temporal sulcus, orbitofrontal cortex, fusiform gyrus, medial prefrontal
      cortex, and insula have been implicated in social processing. Neuroimaging
      studies have demonstrated both anatomical and functional differences in these
      areas of the brain in individuals with ASD when compared to controls; however,
      research on the neural basis for response to treatment in ASD is limited. Results
      of the three studies that have examined the neural mechanisms underlying
      treatment response are promising; following treatment, the brains of individuals
      with ASD seem to "normalize," responding more similarly to those of typically
      developing individuals. The research in this area is in its early stages, and
      thus a focused effort examining the neural basis of treatment response in ASD is
      crucial. 

PMID- 24309260
TI  - Computerized cognitive training targeting brain plasticity in schizophrenia.
AB  - Two important paradigm shifts have occurred recently in the field of
      schizophrenia research. First, we now understand schizophrenia to be a
      neurodevelopmental disorder, one that is characterized by aberrant patterns of
      activation and connectivity in cortical and subcortical neural networks that are
      present before illness onset and that worsen as an individual progresses into
      later stages of the disease. Second, we now understand that these abnormalities
      are not immutable and fixed, but instead can respond to interventions targeting
      brain plasticity, particularly when delivered in the prodromal and early phases
      of schizophrenia. In this chapter, we will first describe some of the
      neurocognitive impairments that characterize schizophrenia, highlighting the
      developmental course of the illness. We will then briefly review salient features
      of currently available computerized cognitive training programs that target these
      impairments. Next, we will present an overview of current research findings
      regarding neurobiological effects of computerized cognitive training in
      schizophrenia and how these results shed light on the critical neuroplasticity
      mechanisms that support successful training. Finally, we will present
      recommendations for future research to optimize computerized cognitive training
      programs, with an aim to promoting functional recovery. 

PMID- 24309261
TI  - The nonspatial side of spatial neglect and related approaches to treatment.
AB  - In addition to deficits in spatial attention, individuals with persistent spatial
      neglect almost universally exhibit nonspatially lateralized deficits in sustained
      and selective attention, and working memory. However, nonspatially lateralized
      deficits in neglect have received considerably less attention in the literature
      than deficits in spatial attention. This is in spite of the fact that
      nonspatially lateralized deficits better predict the chronicity and functional
      disability associated with neglect than spatially lateralized deficits.
      Furthermore, only a few treatment studies have specifically targeted nonspatially
      lateralized deficits as a means to improve spatial neglect. In this chapter, we
      will briefly review several models of spatial attention bias in neglect before
      focusing on nonspatial deficits and the mechanisms of nonspatial-spatial
      interactions and implications for treatment. Treatment approaches that more
      completely address nonspatial deficits and better account for their interactions
      with spatial attention will likely produce better outcomes. 

PMID- 24309259
TI  - Targeting plasticity with vagus nerve stimulation to treat neurological disease.
AB  - Pathological neural activity in a variety of neurological disorders could be
      treated by directing plasticity to specifically renormalize aberrant neural
      circuits, thereby restoring normal function. Brief bursts of acetylcholine and
      norepinephrine can enhance the neural plasticity associated with coincident
      events. Vagus nerve stimulation (VNS) represents a safe and effective means to
      trigger the release of these neuromodulators with a high degree of temporal
      control. VNS-event pairing can generate highly specific and long-lasting
      plasticity in sensory and motor cortex. Based on the capacity to drive specific
      changes in neural circuitry, VNS paired with experience has been successful in
      effectively ameliorating animal models of chronic tinnitus, stroke, and
      posttraumatic stress disorder. Targeted plasticity therapy utilizing VNS is
      currently being translated to humans to treat chronic tinnitus and improve motor
      recovery after stroke. This chapter will discuss the current progress of VNS
      paired with experience to drive specific plasticity to treat these neurological
      disorders and will evaluate additional future applications of targeted plasticity
      therapy. 

PMID- 24309263
TI  - Constraint-induced movement therapy: a method for harnessing neuroplasticity to
      treat motor disorders.
AB  - Constraint-Induced Movement therapy or CI therapy is an approach to physical
      rehabilitation elaborated from basic neuroscience and behavioral research with
      primates. The application of the CI therapy protocol to humans began with the
      upper extremity after stroke and was then modified and extended to cerebral palsy
      in young children, traumatic brain injury, and multiple sclerosis. A form of CI
      therapy was developed for the lower extremities and has been used effectively
      after stroke, spinal cord injury, fractured hip, multiple sclerosis, and cerebral
      palsy. Adaptations of the CI therapy paradigm have also been developed for
      aphasia, focal hand dystonia in musicians, and phantom limb pain. Human and
      animal studies using a variety of methods provide evidence that CI therapy
      produces marked neuroplastic changes in the structure and function of the CNS.
      Moreover, these changes appear to be important for the intervention's therapeutic
      effect. 

PMID- 24309264
TI  - Novelty interventions to enhance broad cognitive abilities and prevent dementia:
      synergistic approaches for the facilitation of positive plastic change.
AB  - Process-based cognitive trainings (PCTs) and novelty interventions are two
      traditional approaches aiming to prevent cognitive decline and dementia. However,
      both have their limitations. PCTs improve performance only in cognitive tests
      similar to the training tasks with inconsistent transfer effects on dissimilar
      tests. We argue that this learning specificity is due to a low training task
      variability. Novelty interventions are characterized by a high task variability
      but do not target specific processing demands affected in aging and dementia. To
      overcome the limitations of both approaches, we developed a process-based novelty
      intervention using a card and board game-based training approach. Here, we use
      highly variable tasks, which overlap in targeted processing demands ("overlapping
      variability" framework). Another nontraditional training approach combines
      cognitively with physically challenging tasks to induce multimechanistic effects,
      which might even interact positively. Initial results of both synergistic
      approaches indicate their potential to enhance broad cognitive abilities and
      prevent dementia. 

PMID- 24309266
TI  - Neuroplasticity: introduction.

PMID- 24309262
TI  - A cognitive framework for understanding and improving interference resolution in
      the brain.
AB  - All of us are familiar with the negative impact of interference on achieving our
      task goals. We are referring to interference by information, which either
      impinges on our senses from an external environmental source or is internally
      generated by our thoughts. Informed by more than a decade of research on the
      cognitive and neural processing of interference, we have developed a framework
      for understanding how interference impacts our neural systems and especially how
      it is regulated and suppressed during efficient on-task performance. Importantly,
      externally and internally generated interferences have distinct neural
      signatures, and further, distinct neural processing emerges depending on whether
      individuals must ignore and suppress the interference, as for distractions, or
      engage with them in a secondary task, as during multitasking. Here, we elaborate
      on this cognitive framework and how it changes throughout the human lifespan,
      focusing mostly on research evidence from younger adults and comparing these
      findings to data from older adults, children, and cognitively impaired
      populations. With insights gleaned from our growing understanding, we then
      describe three novel translational efforts in our lab directed at improving
      distinct aspects of interference resolution using cognitive training. Critically,
      these training approaches were specifically developed to target improved
      interference resolution based on neuroplasticity principles and have shown much
      success in randomized controlled first version evaluations in healthy aging. Our
      results show not only on-task training improvements but also robust
      generalization of benefit to other cognitive control abilities. This research
      showcases how an in-depth understanding of neural mechanisms can then inform the
      development of effective deficit-targeted interventions, which can in turn
      benefit both healthy and cognitively impaired populations. 

PMID- 24309265
TI  - Decoding speech for understanding and treating aphasia.
AB  - Aphasia is an acquired language disorder with a diverse set of symptoms that can
      affect virtually any linguistic modality across both the comprehension and
      production of spoken language. Partial recovery of language function after injury
      is common but typically incomplete. Rehabilitation strategies focus on behavioral
      training to induce plasticity in underlying neural circuits to maximize
      linguistic recovery. Understanding the different neural circuits underlying
      diverse language functions is a key to developing more effective treatment
      strategies. This chapter discusses a systems identification analytic approach to
      the study of linguistic neural representation. The focus of this framework is a
      quantitative, model-based characterization of speech and language neural
      representations that can be used to decode, or predict, speech representations
      from measured brain activity. Recent results of this approach are discussed in
      the context of applications to understanding the neural basis of aphasia symptoms
      and the potential to optimize plasticity during the rehabilitation process. 

PMID- 24309267
TI  - Application of the 2012 revised diagnostic definitions for paediatric multiple
      sclerosis and immune-mediated central nervous system demyelination disorders.
AB  - BACKGROUND: Recently, the International Paediatric Multiple Sclerosis Study Group
      (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating
      syndromes (ADS) of the central nervous system, including paediatric multiple
      sclerosis (MS), have been revised. OBJECTIVE: To evaluate the 2012 revised IPMSSG
      consensus definitions in a cohort of children with ADS prospectively followed
      from January 2007. METHODS: Children with ADS who had an MRI scan obtained within
      90 days after first disease onset were included. The sensitivity and specificity
      of the 2007 and 2012 IPMSSG consensus definitions were assessed. The time to MS
      diagnosis applying the 2007 and 2012 definitions was compared using survival
      analysis and log-rank test. RESULTS: 82 children with ADS were included. 35
      children were diagnosed with paediatric MS, of whom 30 experienced a second
      clinical event. The final diagnosis corresponded applying either the 2007 or 2012
      IPMSSG definitions. The revised 2012 definitions had sufficient sensitivity (80%)
      and high specificity (100%). MS diagnosis was made 3.4 months earlier
      (chi(2)=8.24, p=0.004) applying the new definitions. In 14 children, MS diagnosis
      was made at first MRI. CONCLUSIONS: MS diagnosis can be made reliable and early
      using the 2012 IPMSSG consensus definitions. This is beneficial for adequate
      counselling of children and their families and for early treatment possibilities.

PMID- 24309268
TI  - Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
      are progressive neurodegenerative disorders that share significant clinical,
      pathological and genetic overlap and are considered to represent different ends
      of a common disease spectrum. Mutations in Profilin1 have recently been described
      as a rare cause of familial ALS. The PFN1 E117G missense variant has been
      described in familial and sporadic cases, and also found in controls, casting
      doubt on its pathogenicity. Interpretation of such variants represents a
      significant clinical-genetics challenge. OBJECTIVE AND RESULTS: Here, we combine
      a screen of a new cohort of 383 ALS patients with multiple-sequence datasets to
      refine estimates of the ALS and FTD risk associated with PFN1 E117G. Together,
      our cohorts add up to 5118 ALS and FTD cases and 13 089 controls. We estimate a
      frequency of E117G of 0.11% in controls and 0.25% in cases. Estimated odds after
      population stratification is 2.44 (95% CI 1.048 to infinity, Mantel-Haenszel test
      p=0.036). CONCLUSIONS: Our results show an association between E117G and ALS,
      with a moderate effect size.

PMID- 24309269
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy: search for factors
      associated with treatment dependence or successful withdrawal.
AB  - BACKGROUND: About 40% of responders to treatment for chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) remain treatment dependent and have a
      relapse if treatment is interrupted. OBJECTIVE: To look for factors associated
      with treatment dependence or successful withdrawal in CIDP patients. METHODS: We
      retrospectively studied 70 responder CIDP patients comprising 34 patients who
      remained treatment dependent (treatment-dependent group) and 36 patients whose
      treatment could be discontinued (treatment withdrawal group). Clinical,
      biological, electrophysiological and therapeutic features were compared between
      these groups. RESULTS: A multifocal deficit was more frequent in the treatment
      dependent group (35%) than in the treatment withdrawal group (8%) (p<0.01). The
      most frequent effective treatment was intravenous immunoglobulin (IVIG) for the
      treatment-dependent group (79%). In this group, more patients were resistant to
      corticosteroids in first-line therapy (93%) than in the treatment withdrawal
      group (40%) (p=0.002). The delay to effective treatment was significantly shorter
      for the treatment withdrawal group than for the treatment-dependent group (mean
      11.1 vs 31.2 months; p<0.01). The rate of successful withdrawal was lower with
      IVIG (29%) than with corticosteroids (83%) (p<0.001). CONCLUSIONS: When compared
      with the treatment withdrawal group, the treatment-dependent group was more
      frequently responsive to IVIG, more frequently resistant to corticosteroids in
      first-line treatment, had a longer delay to effective treatment and was more
      likely to present a multifocal deficit. The rate of successful withdrawal seems
      to be higher with corticosteroids, but a prospective study with a long-term
      follow-up is needed to confirm these features.

PMID- 24309270
TI  - Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal
      dementia carrying a C9orf72 repeat expansion or a GRN mutation.
AB  - OBJECTIVES: About a half of patients with frontotemporal dementia (FTD) has
      deposition of phosphorylated TDP-43 protein (pTDP-43) in the brain. We studied
      pTDP-43 and total TDP-43 levels in plasma and cerebrospinal fluid (CSF) in
      healthy controls and patients with FTD, including those carrying a repeat
      expansion in the C9orf72 gene or a mutation in GRN. METHODS: We included 88
      plasma samples of 10 C9orf72 expansion carriers, 5 GRN mutation carriers, 51
      patients with FTD without a known mutation and 22 healthy controls. We also
      obtained CSF samples from 25 patients with FTD (2 with C9orf72 expansion and 3
      with a GRN mutation) and 22 healthy controls. We measured pTDP-43 and total TDP
      43 levels using sandwich ELISA. RESULTS: Patients carrying the C9orf72 repeat
      expansion or a GRN mutation had significantly higher plasma and CSF levels of
      pTDP-43 than the remaining patients with FTD (p<0.05). In addition, plasma pTDP
      43 levels were higher in patients with FTD carrying a C9orf72 expansion or GRN
      mutations than in healthy controls (p<0.05). CONCLUSIONS: Our study shows that
      plasma pTDP-43 levels may be increased in some genetic forms of FTD known to be
      associated with TDP-43 proteinopathies.

PMID- 24309272
TI  - Casparian strips.

PMID- 24309271
TI  - Microplastic moves pollutants and additives to worms, reducing functions linked
      to health and biodiversity.
AB  - Inadequate products, waste management, and policy are struggling to prevent
      plastic waste from infiltrating ecosystems [1, 2]. Disintegration into smaller
      pieces means that the abundance of micrometer-sized plastic (microplastic) in
      habitats has increased [3] and outnumbers larger debris [2, 4]. When ingested by
      animals, plastic provides a feasible pathway to transfer attached pollutants and
      additive chemicals into their tissues [5-15]. Despite positive correlations
      between concentrations of ingested plastic and pollutants in tissues of animals,
      few, if any, controlled experiments have examined whether ingested plastic
      transfers pollutants and additives to animals. We exposed lugworms (Arenicola
      marina) to sand with 5% microplastic that was presorbed with pollutants
      (nonylphenol and phenanthrene) and additive chemicals (Triclosan and PBDE-47).
      Microplastic transferred pollutants and additive chemicals into gut tissues of
      lugworms, causing some biological effects, although clean sand transferred larger
      concentrations of pollutants into their tissues. Uptake of nonylphenol from PVC
      or sand reduced the ability of coelomocytes to remove pathogenic bacteria by
      >60%. Uptake of Triclosan from PVC diminished the ability of worms to engineer
      sediments and caused mortality, each by >55%, while PVC alone made worms >30%
      more susceptible to oxidative stress. As global microplastic contamination
      accelerates, our findings indicate that large concentrations of microplastic and
      additives can harm ecophysiological functions performed by organisms. 

PMID- 24309273
TI  - Gap junctions.
AB  - In vertebrates and invertebrates, signaling among neurons is most commonly
      mediated by chemical synapses. At these synapses neurotransmitter released by
      presynaptic neurons is detected by receptors on the postsynaptic neurons, leading
      to an influx of ions through the receptors themselves or through channels
      activated by intracellular signaling downstream of the receptors. But neurons can
      communicate with each other in a more direct way, by passing signals composed of
      small molecules and ions through pores called gap junctions. Gap junctions that
      transmit electrical signals are called electrical synapses. Unlike most chemical
      synapses, electrical synapses interact through axon-to-axon or dendrite-to
      dendrite contacts. Found throughout the nervous system, they are probably best
      known for linking the relatively few inhibitory, GABAergic, neurons into large,
      effective networks within vertebrate brains. They are particularly important
      early in development before the formation of most chemical synapses, but recent
      work shows gap junctions play important roles in the adult nervous system, too.
      Gap junctions are sometimes thought to be mere passageways between cells. But, as
      recent work shows, their properties can be complex and surprising. Gap junctions
      help generate, propagate, and regulate neural oscillations, can filter electrical
      signals, and can be modulated in a variety of ways. Here we discuss recent work
      highlighting the diversity and importance of gap junctions throughout the nervous
      system. 

PMID- 24309274
TI  - Microplastic ingestion decreases energy reserves in marine worms.
AB  - The indiscriminate disposal of plastic to the environment is of concern.
      Microscopic plastic litter (<5 mm diameter; 'microplastic') is increasing in
      abundance in the marine environment, originating from the fragmentation of
      plastic items and from industry and personal-care products [1]. On highly
      impacted beaches, microplastic concentrations (<1mm) can reach 3% by weight,
      presenting a global conservation issue [2]. Microplastics are a novel substrate
      for the adherence of hydrophobic contaminants [1], deposition of eggs [3], and
      colonization by unique bacterial assemblages [4]. Ingestion by indiscriminate
      deposit-feeders has been reported, yet physical impacts remain understudied [1].
      Here, we show that deposit-feeding marine worms maintained in sediments spiked
      with microscopic unplasticised polyvinylchloride (UPVC) at concentrations
      overlapping those in the environment had significantly depleted energy reserves
      by up to 50% (Figure 1). Our results suggest that depleted energy reserves arise
      from a combination of reduced feeding activity, longer gut residence times of
      ingested material and inflammation. 

PMID- 24309275
TI  - Evidence of episodic-like memory in cuttlefish.
AB  - The recollection of past experiences allows us to recall what happened during a
      particular event, and where and when it occurred [1]. Since the first study on
      episodic-like memory in scrub-jays [2], there has been widespread acceptance of
      the idea that tests in animals should integrate the 'what', 'where' and 'when'
      components of a unique event that occurred in the past [3,4]. This is referred to
      as episodic-like memory rather than episodic memory per se, in acknowledgement of
      the lack of evidence for, or against, the phenomenological aspects that accompany
      episodic recollection in humans. So far, evidence for episodic-like memory has
      only been found in some birds and mammals. We show here that cuttlefish,
      cephalopod mollusks, keep track of what they have eaten, and where and how long
      ago they ate, in order to match their foraging behavior with the time of
      replenishing of different foods. Foraging in cuttlefish fulfils the criteria of
      'what', 'where' and 'when' of unique events and thus provides behavioral evidence
      of episodic-like memory in an invertebrate. 

PMID- 24309276
TI  - Koalas use a novel vocal organ to produce unusually low-pitched mating calls.
AB  - During the breeding season, male koalas produce 'bellow' vocalisations that are
      characterised by a continuous series of inhalation and exhalation sections, and
      an extremely low fundamental frequency (the main acoustic correlate of perceived
      pitch) [1]. Remarkably, the fundamental frequency (F0) of bellow inhalation
      sections averages 27.1 Hz (range: 9.8-61.5 Hz [1]), which is 20 times lower than
      would be expected for an animal weighing 8 kg [2] and more typical of an animal
      the size of an elephant (Supplemental figure S1A). Here, we demonstrate that
      koalas use a novel vocal organ to produce their unusually low-pitched mating
      calls. 

PMID- 24309277
TI  - Aging: filtering out bad mitochondria.
AB  - During yeast cytokinesis an aged mother cell gives rise to an immaculate daughter
      cell. A new study now demonstrates that this rejuvenation encompasses a novel
      Sir2- and actin-cable-dependent filtering process that prevents feeble
      mitochondria from entering the daughter cell. 

PMID- 24309278
TI  - Body perception: intersensory origins of self and other perception in newborns.
AB  - Self-perception involves integrating changes in visual, tactile, and
      proprioceptive stimulation from self-motion and discriminating these changes from
      those of other objects. Recent evidence suggests even newborns discriminate
      synchronous from asynchronous visual-tactile stimulation to their own body, a
      foundation for self-perception. 

PMID- 24309279
TI  - Evolution: sex or survival.
AB  - A classic paradox in sexual selection is how sexual traits under strong
      directional selection maintain underlying genetic variation. A new study has
      found that in Soay sheep a trade-off between reproductive success and survival
      maintains variation in horn size. 

PMID- 24309280
TI  - Colour vision: parallel pathways intersect in Drosophila.
AB  - In the last one hundred years, colour vision has been demonstrated in bees and
      many other insects. But the underlying neural wiring remained elusive. A new
      study on Drosophila melanogaster combining behavioural and genetic tools yields
      surprising insights. 

PMID- 24309281
TI  - Nuclear division: giving daughters their fair share.
AB  - How do nuclear components, apart from chromosomes, partition equally to daughter
      nuclei during mitosis? In Schizosaccharomyces japonicus, the conserved LEM-domain
      nuclear envelope protein Man1 ensures the formation of identical daughter nuclei
      by coupling nuclear pore complexes to the segregating chromosomes. 

PMID- 24309282
TI  - Cell biology: up against the wall.
AB  - Lignin is deposited in precise patterns in some cell types. Two recent papers
      provide insights into how this is achieved in the Casparian strip of the root
      endodermis where a discrete band of lignin is crucial to regulating the passage
      of water and solutes. 

PMID- 24309283
TI  - Circadian rhythms: hijacking the cyanobacterial clock.
AB  - Using basic research to advance a practical application, a recent study
      demonstrates that the circadian clock in cyanobacteria can be 'reprogrammed' to
      improve yields of heterologous protein production - a green future surely
      beckons. 

PMID- 24309284
TI  - Mitochondrial disease: mtDNA and protein segregation mysteries in iPSCs.
AB  - Mitochondrial diseases cause a range of clinical manifestations even in patients
      carrying the same mtDNA mutations. New work reveals that a common disease
      associated mtDNA mutation is selectively segregated from wild-type mtDNA during
      the reprogramming of induced pluripotent stem cells and that high levels of this
      mutation in differentiated neurons upregulate Parkin-mediated mitophagy. 

PMID- 24309285
TI  - Gene regulation: when analog beats digital.
AB  - Why do some genes seem to respond in a 'digital', on/off manner to a graded
      signal, while others produce an 'analog', graded response? A new study suggests
      that the DNA-binding properties of transcription factors can strongly influence
      the response patterns of gene networks. 

PMID- 24309286
TI  - What we know currently about mirror neurons.
AB  - Mirror neurons were discovered over twenty years ago in the ventral premotor
      region F5 of the macaque monkey. Since their discovery much has been written
      about these neurons, both in the scientific literature and in the popular press.
      They have been proposed to be the neuronal substrate underlying a vast array of
      different functions. Indeed so much has been written about mirror neurons that
      last year they were referred to, rightly or wrongly, as "The most hyped concept
      in neuroscience". Here we try to cut through some of this hyperbole and review
      what is currently known (and not known) about mirror neurons. 

PMID- 24309287
TI  - Vasodilation and radical-scavenging activity of imperatorin and selected
      coumarinic and flavonoid compounds from genus Casimiroa.
AB  - Hypertension is a very widespread condition which is not strictly considered as
      an illness but if not countered, progressively causes damage to all tissues and
      loss in their functionality. For this reason the find of new antihypertensive
      agents is prominent and medicinal plants and their derivatives are valuable for
      the purpose. The genus Casimiroa (Rutaceae) includes plants from Central America
      and Mexico; among these, Casimiroa edulis Llave et Lex. and Casimiroa pubescens
      Ramirez are the most relevant species, even for their medicinal uses. The
      decoction of leaves and seeds is traditionally taken as a tea mainly to lower
      blood pressure. The object of this research was the study of vascular activity of
      coumarinic and flavonoid compounds isolated from seeds of Casimiroa spp. in
      comparison with Casimiroa edulis and Casimiroa pubescens extracts. The phenolic
      compounds isolated from Casimiroa were herniarin (Her), imperatorin (Imp), 8
      geranyloxypsoralen (GOP) and 5,6,2',3',4'-pentamethoxyflavone (PMF). All these
      compounds induced vasorelaxation on rat arterial tissues although with different
      effectiveness. To study the cellular mechanisms of the vasorelaxation exhibited
      by imperatorin, we used selective inhibitors of different receptors and enzymes,
      such as atropine, pyrilamine, nifedipine, L-NAME and DETC. In a further step of
      this research, we evaluated the radical-scavenging activity of Casimiroa extracts
      and isolated compounds by means of DPPH assay. In general, we observed that the
      scavenging activities increased in a concentration-dependent manner for all
      substances. The phenolic compounds highlight a synergism of vasodilation and
      antioxidant activity which may be very useful in the management of cardiovascular
      diseases. Among the evaluated compounds, imperatorin shows a significant
      vasorelaxant activity even higher than acetylcholine and similar to nitrite, and
      also useful antiradical capabilities. All these properties suggest its possible
      role against hypertension and vasculopathies, even if in vivo studies are needed
      to determine the actual applications. 

PMID- 24309288
TI  - Resveratrol protects RPE cells from sodium iodate by modulating PPARalpha and
      PPARdelta.
AB  - Selective killing of RPE cells in vivo by sodium iodate develops cardinal
      phenotypes of atrophic age-related macular degeneration. However, the molecular
      mechanisms are elusive. We tried to search for small cyto-protective molecules
      against sodium iodate and explore their mechanisms of action. Sodium iodate
      mediated RPE cell death was associated with increased levels of reactive oxygen
      species (ROS) and IL-8. Resveratrol, a natural occurring polyphenol compound, was
      found to strongly protect RPE cells from sodium iodate with inhibition of
      production of ROS and IL-8. Resveratrol activated all isoforms of PPARs.
      Treatment with PPARalpha and PPARdelta agonists inhibited sodium iodate-induced
      ROS production and protected RPE cells from sodium iodate. A PPARalpha antagonist
      significantly reduced resveratrol's protection of RPE cells from sodium iodate.
      Paradoxically, knocking down PPARdelta also rendered RPE cells resistant to
      sodium iodate. Moreover, PPAR agonists reversed sodium iodate-induced production
      of IL-8. However, neutralizing extracellular IL-8 failed to protect RPE cells
      from sodium iodate. Taken together, these observations show that resveratrol
      protects RPE cells from sodium iodate injury through the activation of PPARalpha
      and alteration of PPARdelta conformation. PPARalpha and delta modulators might
      ameliorate stress-induced RPE degeneration in vivo. 

PMID- 24309289
TI  - Abdominal aortic thrombosis associated with nephrotic syndrome.

PMID- 24309290
TI  - RNA interference of a heat shock protein, Hsp70, loses its protection role in
      indirect chilling injury to the beet armyworm, Spodoptera exigua.
AB  - The beet armyworm, Spodoptera exigua, is freeze-susceptible, in which glycerol
      plays a crucial role in depressing supercooling point (SCP) to avoid the freezing
      injury. This study focused on a non-freezing injury classified into indirect
      chilling injury of S. exigua after a prolonged exposure to low temperatures much
      above SCPs. Exposure to 0 and 5 degrees C for longer than 2weeks was lethal to
      all the immature stages. Among immature stages, eggs were the most susceptible to
      the low temperature treatments and pupae were the next susceptible. Among larvae,
      the third instar (L3) appeared to be more tolerant than the fifth instar (L5).
      The temperature treatment at 15 degrees C allowed both L3 and L5 to exhibit a
      feeding behavior and induced little non-freezing injury, suggesting a minimal
      temperature threshold for optimal overwintering conditions of S. exigua. Three
      heat shock protein genes (Hsp70, Hsp74, Hsp83) were expressed in the larvae at
      the low temperature treatments. Only Hsp70 was inducible to the low temperatures
      in both L3 and L5 stages. RNA interference of Hsp70 expression led to
      significantly lose the survival rates of the treated larvae in the conditions
      inducing the non-freezing injury. These results suggest that Hsp70 plays a role
      in protecting S. exigua from the indirect chilling injury. 

PMID- 24309291
TI  - Association between the SORL1 rs2070045 polymorphism and late-onset Alzheimer's
      disease: interaction with the ApoE genotype in the Chinese Han population.
AB  - Late-onset Alzheimer's Disease (LOAD) is a common neurodegenerative disease [1],
      and the two well identified pathological hallmarks of LOAD are senile plaques
      formed from amyloid beta peptides (Abeta) and neurofibrillary tangles (NFTs)
      consisting of hyperphorylated tau protein [2]. The neuronal Sortilin-related
      receptor (SORL1) is involved in the processing and trafficking of amyloid
      precursor protein (APP) into recycling pathways, thus influencing Abeta
      generation and by this AD pathology [3]. To explore the relationship between the
      single nucleotide polymorphism (SNP) of the SORL1 SNP 19 rs2070045 and LOAD, a
      case-control study was conducted in a Chinese Han cohort including 77 LOAD
      patients and 100 control participants. This SNP 19 rs2070045 was genotyped with a
      polymerase chain reaction-restriction fragment length polymorphism, (PCR-RFLP)
      method. The association was revealed between the polymorphism of SNP 19 rs2070045
      (T/T, T/G, G/G) and the risk of LOAD. The results of this study indicated that
      the T allele (T/G+T/T) of SNP 19 rs2070045 was successful in exerting obvious
      influence in LOAD patients (chi(2)=4.884, P=0.027<0.05). However, there is no
      sufficient evidence to prove that the T allele of SNP 19 rs2070045 is associated
      with E4 allele of ApoE gene in LOAD patients (chi(2)=0.771, P=0.380>0.05). 

PMID- 24309292
TI  - Acute DSS colitis alters EphB6 receptor expression in neurons of the spinal
      dorsal horn.
AB  - The ephrin family of receptors (Eph) and their ephrin ligands are involved in
      pain associated hyperalgesia, but the underlying mechanisms involved have not
      been fully elucidated. The EphB6 receptor is a distinctive member of the EphB
      subclass in that its kinase domain contains several alterations in the conserved
      amino acids and thus lacks catalytic activity. We sought to identify a role for
      EphB6 in inflammatory pain, with the murine dextran sulfate sodium (DSS) colitis
      model of inflammatory bowel disease (IBD). Colitis, induced with the
      administration of 4% (wt./vol.) DSS in the drinking water, significantly
      decreased EphB6 protein expression levels in neurons of the lower thoracic
      superficial layers of spinal dorsal horns, the location of neurons that receive
      the majority of nociceptive information from the colon, via the primary
      afferents. A shift towards increased EphB/ephrinB forward signaling, mediated by
      EphB6 down-regulation in neurons of the dorsal horn, may play a role in
      inflammatory pain caused by IBD. 

PMID- 24309293
TI  - Basic fibroblast growth factor is a key factor that induces bone marrow
      mesenchymal stem cells towards cells with Schwann cell phenotype.
AB  - Bone marrow mesenchymal stem cells (MSCs) can be differentiate towards a Schwann
      cells (SCs) lineage when exposed to pre-inducing reagents beta-mercaptoethanol
      (BME) and retinoic acid (RA), followed by inducing factors: forskolin (FSK),
      basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), and
      heregulin (HRG). However, the underlying mechanisms remain unclear. Here, we
      investigated the individual effects of these inducing factors on the
      differentiation of MSCs towards SC phenotype in rats. We show that the omission
      of either HRG or PDGF from the induction medium is not sufficient to change the
      SC-like phenotype or the expression level of the SC marker, S100beta. However,
      the omission of bFGF from the induction medium effectively blocked neural
      induction of the MSCs. Moreover, only bFGF was found to inhibit MSC proliferation
      during differentiation. To clarify the mechanism responsible for the effect of
      bFGF, we also investigated the activation of the extracellular signal-regulated
      kinase (ERK) pathway in the induced cells. Our results suggest that morphological
      changes in MSCs induced by bFGF depend on the activation of ERK, and bFGF may be
      an indispensable factor that induces MSCs to differentiate into cells with SCs
      phenotype. 

PMID- 24309294
TI  - Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term
      potentiation impairment in rats.
AB  - Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts
      a wide range of biological activities on the central nervous system. We have
      previously reported that CCK-8 significantly alleviated morphine-induced amnesia
      and reversed spine density decreases in the CA1 region of the hippocampus in
      morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term
      potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of
      rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population
      spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG
      region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated
      hippocampal LTP and CCK-8 (1MUg, i.c.v.) restored the amplitude of PS that was
      attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and
      1MUg, i.c.v.) also significantly augmented hippocampal LTP in saline-treated
      (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260
      (10MUg, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L
      364,718 (10MUg, i.c.v) did not. The present results demonstrate that CCK-8
      attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and
      suggest an ameliorative function of CCK-8 on morphine-induced memory impairment. 

PMID- 24309295
TI  - The magnitude and reliability of cue-specific craving in nondependent smokers.
AB  - BACKGROUND: Cue-reactivity is a robust phenomenon in regular cigarette smokers
      (Carter and Tiffany, 1999), but it has not been widely investigated in
      nondependent smokers. Further, most research on cue-specific craving assesses
      response to cues in a single experimental session. As such, investigations of cue
      specific craving have primarily measured state-like but not trait-like responses
      to smoking stimuli. METHODS: This study measured general and cue-specific craving
      in nondependent smokers and assessed the within-session and cross-session
      reliability of these two facets of craving. Participants (n=154) attended five
      laboratory sessions over the course of three months and completed multiple cue
      reactivity trials (using smoking and neutral in vivo and photographic stimuli)
      during each study visit. RESULTS: Results indicated that smoking cues elicited
      significantly stronger craving than neutral cues across study sessions, and that
      craving ratings following smoking cues decreased across subsequent sessions.
      Within-session and cross-session reliability was extremely high. CONCLUSIONS:
      Overall, findings indicate that nondependent smokers experience reactivity to
      smoking cues, and that this response is quite reliable within and across
      sessions. Further, the magnitude of cue-specific craving was comparable to what
      has been observed in heavy, dependent smokers.

PMID- 24309296
TI  - First-year college students' interest in trying dissolvable tobacco products.
AB  - BACKGROUND: Dissolvable tobacco products (DTPs) have been introduced into test
      markets in the U.S. We sought to gauge the level of interest in trying these
      products and correlates of interest among potential consumers. METHODS: A web
      based survey of freshman at 11 universities in North Carolina and Virginia was
      conducted in fall 2010. Multivariable logistic regression analyses were used to
      identify correlates of students' likelihood to try DTPs if offered a free sample.
      RESULTS: Weighted prevalence of likelihood to try DTPs was 3.7%. Significant
      correlates of likelihood to try included male gender, current cigarette smoking,
      current snus use, sensation seeking, lifetime illicit drug use, and perceived
      health risk of using DTPs. Among current smokers, current snus use, current use
      of chewing tobacco, and considering quitting smoking were associated with
      likelihood to try DTPs. CONCLUSIONS: While overall interest in trying these
      products was low, current users of cigarettes and snus were much more likely than
      others in trying a free sample. Some current smokers may consider DTPs to be an
      aid to smoking cessation, although the population-level impact of introducing
      these products is unknown.

PMID- 24309298
TI  - The Public Health Responsibility Deal: brokering a deal for public health, but on
      whose terms?
AB  - Coalitions of multinational food and drink businesses have pledged to reformulate
      their products and to market them responsibly. Largely business-led and self
      regulated, the integrity of these voluntary initiatives has been questioned. The
      Public Health Responsibility Deal in England is an example of a voluntary
      initiative that is government-led. Does this approach provide evidence that with
      public leadership there is potential for voluntary actions to deliver meaningful
      results for public health? METHODS: The subject of the research is the calorie
      reduction initiative of the Responsibility Deal. Source material was obtained
      primarily through a series of UK Freedom of Information requests and comprises
      previously unpublished Department of Health documentation relating to relevant
      meetings held during 2011 and 2012. RESULTS: The Responsibility Deal approach to
      calorie reduction deliberately involves the food industry in the specification of
      the measures it is to implement (reformulation and portion control). Finding the
      common ground between private and public interests has resulted in the deflection
      of public health objectives and the preclusion of adequate monitoring and
      evaluation. CONCLUSIONS: The Responsibility Deal approach is fundamentally flawed
      in its expectation that industry will take voluntary actions that prioritise
      public health interests above its own. Being government-led counts for little in
      the absence of sanctions to drive compliance. Instead the initiative affords
      private interests the opportunity to influence in their favour the public health
      policies and strategies that affect their products.

PMID- 24309297
TI  - Concordance between self-reported substance use and toxicology among HIV-infected
      and uninfected at risk youth.
AB  - BACKGROUND: Substance use by youth living with HIV (YLWH) is a concern, given
      potential interactions with virus-associated immune suppression and adverse
      effects on risk behaviors, neurocognition, and adherence. Self-report substance
      use measures provide efficient cost-effective assessments. Analyses describe self
      reported substance use among YLWH and examine agreement with toxicology assays.
      METHODS: Seventy-eight youth age 18-24 years (87% male, 71% African-American)
      with behaviorally acquired HIV-1 infection and 55 uninfected youth completed the
      Alcohol, Smoking, and Substance Involvement Screening Test to assess drug use
      frequency, including tobacco, marijuana, cocaine, and alcohol, over the prior
      three months. Elisa-based toxicology assays were used to detect 27 substances in
      plasma. Chi-square tests compared substance use between YLWH and uninfected
      youth; Kappa statistics compared agreement between self-report and toxicology.
      RESULTS: YLWH reported marijuana (49%), tobacco (56%), and alcohol (87%) use,
      with 20%, 28% and 3% reporting daily use of each substance, respectively; other
      substance use was uncommon. Uninfected youth reported less tobacco use but
      otherwise similar substance use. All youth who reported daily use of marijuana or
      tobacco had positive plasma toxicology results, while concordance decreased with
      less frequent self-reported use. Among youth reporting no substance use, few
      tested positive (4% YLWH, 2% uninfected youth for cannabis; 8%YLWH for tobacco).
      CONCLUSIONS: Youth report high rates of marijuana, tobacco, and alcohol use.
      Concordance between self-report and toxicology for marijuana and tobacco use,
      particularly for daily users, supports self-report as a valid indicator of
      substance use in research studies of youth with or without HIV-1 infection.

PMID- 24309300
TI  - Acute exercise facilitates brain function and cognition in children who need it
      most: an ERP study of individual differences in inhibitory control capacity.
AB  - The present study examined the effects of moderate-intensity aerobic exercise on
      aspects of cognitive control in two groups of children categorized by higher- and
      lower-task performance. Event-related brain potentials (ERPs) were collected in
      40 preadolescent children during a modified flanker task following 20 min of
      treadmill walking and seated rest on separate occasions. Participants were
      bifurcated into two groups based on task performance following the resting
      session. Findings revealed that following exercise, higher-performers maintained
      accuracy and exhibited no change in P3 amplitude compared to seated rest. Lower
      performers demonstrated a differential effect, such that accuracy measures
      improved, and P3 amplitude increased following exercise. Lastly, both groups
      displayed smaller N2 amplitude and shorter P3 latency following exercise,
      suggesting an overall facilitation in response conflict and the speed of stimulus
      classification. The current findings replicate prior research reporting the
      beneficial influence of acute aerobic exercise on cognitive performance in
      children. However, children with lower inhibitory control capacity may benefit
      the most from single bouts of exercise. These data are among the first to
      demonstrate the differential effect of physical activity on individuals who vary
      in inhibitory control, and further support the role of aerobic exercise for brain
      health during development.

PMID- 24309299
TI  - Caudate responses to reward anticipation associated with delay discounting
      behavior in healthy youth.
AB  - BACKGROUND: Choices requiring delay of gratification made during adolescence can
      have significant impact on life trajectory. Willingness to delay gratification
      can be measured using delay discounting tasks that require a choice between a
      smaller immediate reward and a larger delayed reward. Individual differences in
      the subjective value of delayed rewards are associated with risk for development
      of psychopathology including substance abuse. The neurobiological underpinnings
      related to these individual differences early in life are not fully understood.
      Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that
      individual differences in delay discounting behavior in healthy youth are related
      to differences in responsiveness to potential reward. METHOD: Nineteen 10-14 year
      olds performed a monetary incentive delay task to assess neural sensitivity to
      potential reward and a questionnaire to measure discounting of future monetary
      rewards. RESULTS: Left ventromedial caudate activation during anticipation of
      potential reward was negatively correlated with delay discounting behavior. There
      were no regions where brain responses during notification of reward outcome were
      associated with discounting behavior. CONCLUSIONS: Brain activation during
      anticipation of potential reward may serve as a marker for individual differences
      in ability or willingness to delay gratification in healthy youth.

PMID- 24309301
TI  - The establishment of Saccharomyces boulardii surface display system using a
      single expression vector.
AB  - In the present study, an a-agglutinin-based Saccharomyces boulardii surface
      display system was successfully established using a single expression vector.
      Based on the two protein co-expression vector pSP-G1 built by Partow et al., a S.
      boulardii surface display vector-pSDSb containing all the display elements was
      constructed. The display results of heterologous proteins were confirmed by
      successfully displaying enhanced green fluorescent protein (EGFP) and chicken
      Eimeria tenella Microneme-2 proteins (EtMic2) on the S. boulardii cell surface.
      The DNA sequence of AGA1 gene from S. boulardii (SbAGA1) was determined and used
      as the cell wall anchor partner. This is the first time heterologous proteins
      have been displayed on the cell surface of S. boulardii. Because S. boulardii is
      probiotic and eukaryotic, its surface display system would be very valuable,
      particularly in the development of a live vaccine against various pathogenic
      organisms especially eukaryotic pathogens such as protistan parasites. 

PMID- 24309302
TI  - Mucoadhesive gels designed for the controlled release of chlorhexidine in the
      oral cavity.
AB  - This study describes the in vitro/ex vivo buccal release of chlorhexidine (CHX)
      from nine mucoadhesive aqueous gels, as well as their physicochemical and
      mucoadhesive properties: CHX was present at a constant 1% w/v concentration in
      the chemical form of digluconate salt. The mucoadhesive/gel forming materials
      were carboxymethyl- (CMC), hydroxypropylmethyl- (HPMC) and hydroxypropyl- (HPC)
      cellulose, alone (3% w/w) or in binary mixtures (5% w/w); gels were tested for
      their mucoadhesion using the mucin method at 1, 2 and 3% w/w concentrations. CHX
      release from different formulations was assessed using a USP method and newly
      developed apparatus, combining release/permeation process in which porcine mucosa
      was placed in a Franz cell. The combination of HPMC or HPC with CMC showed slower
      drug release when compared to each of the individual polymers. All the systems
      proved suitable for CHX buccal delivery, being able to guarantee both prolonged
      release and reduced transmucosal permeation. Gels were compared for the release
      of previously studied tablets that contained Carbopol and HPMC, alone or in
      mixture. An accurate selection and combination of the materials allow the design
      of different pharmaceutical forms suitable for different purposes, by simply
      modifying the formulation compositions. 

PMID- 24309304
TI  - Investigation of the Formation Process of Two Piracetam Cocrystals during
      Grinding.
AB  - Cocrystal formation rates during dry grinding and liquid-assisted grinding were
      investigated by X-ray powder diffractometry and Raman spectroscopy. Two
      polymorphic forms of piracetam were used to prepare known piracetam cocrystals as
      model substances, i.e.,piracetam-citric acid and piracetam-tartaric acid
      cocrystals. Raman spectroscopy in combination with principal component analysis
      was used to visualize the cocrystal formation pathways. During dry grinding,
      cocrystal formation appeared to progress via an amorphous intermediate stage,
      which was more evident for the piracetam-citric acid than for the piracetam
      tartaric acid cocrystal. It was shown that liquid-assisted grinding led to faster
      cocrystal formation than dry grinding, which may be explained by the higher
      transformation rate due to the presence of liquid. The cocrystal formation rate
      did not depend on the applied polymorphic form of the piracetam and no
      polymorphic cocrystals were obtained. 

PMID- 24309305
TI  - From Mini to Micro Scale-Feasibility of Raman Spectroscopy as a Process
      Analytical Tool (PAT).
AB  - BACKGROUND: Active coating is an important unit operation in the pharmaceutical
      industry. The quality, stability, safety and performance of the final product
      largely depend on the amount and uniformity of coating applied. Active coating is
      challenging regarding the total amount of coating and its uniformity.
      Consequently, there is a strong demand for tools, which are able to monitor and
      determine the endpoint of a coating operation. In previous work, it was shown
      that Raman spectroscopy is an appropriate process analytical tool (PAT) to
      monitor an active spray coating process in a pan coater [1]. Using a multivariate
      model (Partial Least Squares-PLS) the Raman spectral data could be correlated
      with the coated amount of the API diprophylline. While the multivariate model was
      shown to be valid for the process in a mini scale pan coater (batch size: 3.5 kg
      cores), the aim of the present work was to prove the robustness of the model by
      transferring the results to tablets coated in a micro scale pan coater (0.5 kg).
      METHOD: Coating experiments were performed in both, a mini scale and a micro
      scale pan coater. The model drug diprophylline was coated on placebo tablets. The
      multivariate model, established for the process in the mini scale pan coater, was
      applied to the Raman measurements of tablets coated in the micro scale coater for
      six different coating levels. Then, the amount of coating, which was predicted by
      the model, was compared with reference measurements using UV spectroscopy.
      RESULTS: For all six coating levels the predicted coating amount was equal to the
      amounts obtained by UV spectroscopy within the statistical error. Thus, it was
      possible to predict the total coating amount with an error smaller than 3.6%. The
      root mean squares of errors for calibration and prediction (root mean square of
      errors for calibration and prediction-RMSEC and RMSEP) were 0.335 mg and 0.392
      mg, respectively, which means that the predictive power of the model is not
      dependent on the scale or the equipment. CONCLUSION: The scale-down experiment
      showed that it was possible to transfer the PLS model developed on a mini scale
      coater to a micro scale coater.

PMID- 24309303
TI  - Transporter-mediated drug-drug interactions with oral antidiabetic drugs.
AB  - Uptake transporters (e.g., members of the SLC superfamily of solute carriers) and
      export proteins (e.g., members of the ABC transporter superfamily) are important
      determinants for the pharmacokinetics of drugs. Alterations of drug transport due
      to concomitantly administered drugs that interfere with drug transport may alter
      the kinetics of drug substrates. In vitro and in vivo studies indicate that many
      drugs used for the treatment of metabolic disorders and cardiovascular diseases
      (e.g., oral antidiabetic drugs, statins) are substrates for uptake transporters
      and export proteins expressed in the intestine, the liver and the kidney. Since
      most patients with type 2 diabetes receive more than one drug, transporter
      mediated drug-drug interactions are important molecular mechanisms leading to
      alterations in oral antidiabetic drug pharmacokinetics with the risk of adverse
      drug reactions. This review focuses on uptake transporters of the SLCO/SLC21
      (OATP) and SLC22 (OCT/OAT) family of solute carriers and export pumps of the ABC
      (ATP-binding cassette) transporter superfamily (especially P-glycoprotein) as
      well as the export proteins of the SLC47 (MATE) family and their role for
      transporter-mediated drug-drug interactions with oral antidiabetic drugs. 

PMID- 24309306
TI  - Development of re-usable yeast-gellan gum micro-bioreactors for potential
      application in continuous fermentation to produce bio-ethanol.
AB  - The objectives of this study were to investigate the feasibility of encapsulating
      yeast cells using gellan gum by an emulsification method and to evaluate the
      fermentation efficiency and the reusability of the micro-bioreactors produced. It
      was found that yeast cells could be successfully encapsulated to form relatively
      spherical micro-bioreactors with high specific surface area for mass transfer.
      Cell viability was found to be reduced by one log reduction after the
      emulsification process. The ethanol yield of the micro-bioreactors was comparable
      to that of free yeast in the first fermentation cycle. The micro-bioreactors
      remained intact and could be re-used up to 10 cycles of fermentation. Despite
      cell breakthrough, relatively high ethanol yields were obtained, indicating that
      the micro-bioreactors also functioned as regenerative reservoirs of yeast. 

PMID- 24309307
TI  - Antiretroviral drug interactions: overview of interactions involving new and
      investigational agents and the role of therapeutic drug monitoring for
      management.
AB  - Antiretrovirals are prone to drug-drug and drug-food interactions that can result
      in subtherapeutic or supratherapeutic concentrations. Interactions between
      antiretrovirals and medications for other diseases are common due to shared
      metabolism through cytochrome P450 (CYP450) and uridine diphosphate
      glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p
      glycoprotein, organic anion-transporting polypeptide). The clinical significance
      of antiretroviral drug interactions is reviewed, with a focus on new and
      investigational agents. An overview of the mechanistic basis for drug
      interactions and the effect of individual antiretrovirals on CYP450 and UGT
      isoforms are provided. Interactions between antiretrovirals and medications for
      other co-morbidities are summarized. The role of therapeutic drug monitoring in
      the detection and management of antiretroviral drug interactions is also briefly
      discussed. 

PMID- 24309308
TI  - Role of p-glycoprotein expression and function in cystinotic renal proximal
      tubular cells.
AB  - P-glycoprotein (P-gp) is an ATP-dependent transporter localized at the apical
      membrane of the kidney proximal tubules, which plays a role in the efflux of
      cationic and amphipathic endogenous waste products and xenobiotics, such as
      drugs, into urine. Studies in mice deficient in P-gp showed generalized proximal
      tubular dysfunction similar to the phenotype of patients with cystinosis, an
      autosomal recessive disorder caused by mutations in the lysosomal cystine
      transporter cystinosin. Renal disease in cystinosis is characterized by
      generalized dysfunction of the apical proximal tubular influx transporters (so
      called renal Fanconi syndrome) developing during infancy and gradually
      progressing towards end-stage renal disease before the 10th birthday in the
      majority of patients that are not treated with the cystine-depleting drug
      cysteamine. Here, we investigated whether the proximal tubular efflux transporter
      P-gp is affected in cystinosis and whether this might contribute to the
      development of renal Fanconi syndrome. We used conditionally immortalized (ci)
      proximal tubular epithelial cells (ciPTEC) derived from cystinotic patients and
      healthy volunteers. P-gp-mediated transport was measured by using the P-gp
      substrate calcein-AM in the presence and absence of the P-gp-inhibitor PSC833. P
      gp activity was normal in cystinotic cells as compared to controls. Additionally,
      the effect of cysteamine on P-gp transport activity and phosphate uptake was
      determined; demonstrating increased P-gp activity in cystinotic cells, and
      further decrease of proximal tubular phosphate uptake. This observation is
      compatible with the persistence of renal Fanconi syndrome in vivo under
      cysteamine therapy. In summary, P-gp expression and activity are normal in
      cystinotic ciPTEC, indicating that P-gp dysfunction is not involved in the
      pathogenesis of cystinosis. 

PMID- 24309309
TI  - Encapsulation of natural polyphenolic compounds; a review.
AB  - Natural polyphenols are valuable compounds possessing scavenging properties
      towards radical oxygen species, and complexing properties towards proteins. These
      abilities make polyphenols interesting for the treatment of various diseases like
      inflammation or cancer, but also for anti-ageing purposes in cosmetic
      formulations, or for nutraceutical applications. Unfortunately, these properties
      are also responsible for a lack in long-term stability, making these natural
      compounds very sensitive to light and heat. Moreover, polyphenols often present a
      poor biodisponibility mainly due to low water solubility. Lastly, many of these
      molecules possess a very astringent and bitter taste, which limits their use in
      food or in oral medications. To circumvent these drawbacks, delivery systems have
      been developed, and among them, encapsulation would appear to be a promising
      approach. Many encapsulation methods are described in the literature, among which
      some have been successfully applied to plant polyphenols. In this review, after a
      general presentation of the large chemical family of plant polyphenols and of
      their main chemical and biological properties, encapsulation processes applied to
      polyphenols are classified into physical, physico-chemical, chemical methods, and
      other connected stabilization methods. After a brief description of each
      encapsulation process, their applications to polyphenol encapsulation for
      pharmaceutical, food or cosmetological purposes are presented. 

PMID- 24309310
TI  - Formulation optimization of sustained-release ammonio methacrylate copolymer
      microspheres. Effects of log p and concentration of polar cosolvents, and role of
      the drug/copolymer ratio.
AB  - The objectives of this work were the formulation optimization of the preparation
      process parameters and to evaluate spray-dried sustained-release microspheres
      using ammonio methacrylate copolymer (AMC) as a polymer matrix. The effects of
      log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and
      n-butyl acetate) and different drug/copolymer ratios as independent variables on
      the physicochemical parameters (the W1/O emulsion viscosity, the microsphere
      production yield, the average particle size, the encapsulation efficiency) and
      the cumulative in vitro drug release as dependent variables were studied. The
      optimization was carried out on the basis of the 33 factorial design study. The
      optimization process results showed that addition of polar cosolvents proved
      effective, linear relationships were observed between the independent and the
      dependent variables. The best conditions were achieved by microspheres prepared
      by using a low/medium cosolvent log P, cosolvent concentration of 25-50% v/v and
      a drug/copolymer ratio of 1:16. The microspheres ensured sustained release with
      Nernst and Baker-Lonsdale release profiles. 

PMID- 24309311
TI  - Exploring the correlation between lipid packaging in lipoplexes and their
      transfection efficacy.
AB  - Whilst there is a large body of evidence looking at the design of cationic
      liposomes as transfection agents, correlates of formulation to function remain
      elusive. In this research, we investigate if lipid packaging can give further
      insights into transfection efficacy. DNA lipoplexes composed of 1,2-dioleoyl-sn
      glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine (DSPE) in combination with 1,2-dioleoyl-3-trimethylammonium
      propane (DOTAP) or 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) were prepared
      by the lipid hydration method. Each of the formulations was prepared by hydration
      in dH2O or phosphate buffer saline (PBS) to investigate the effect of buffer
      salts on lipoplex physicochemical characteristics and in vitro transfection. In
      addition, Langmuir monolayer studies were performed to investigate any possible
      correlation between lipid packaging and liposome attributes. Using PBS, rather
      than dH2O, to prepare the lipoplexes increased the size of vesicles in most of
      formulations and resulted in variation in transfection efficacies. However, one
      combination of lipids (DSPE:DOTAP) could not form liposomes in PBS, whilst the
      DSPE:DSTAP combination could not form liposomes in either aqueous media.
      Monolayer studies demonstrated saturated lipid combinations offered dramatically
      closer molecular packing compared to the other combinations which could suggest
      why this lipid combination could not form vesicles. Of the lipoplexes prepared,
      those formulated with DSTAP showed higher transfection efficacy, however, the
      effect of buffer on transfection efficiency was formulation dependent. 

PMID- 24309313
TI  - Formulation patents and dermatology and obviousness.
AB  - Most patents covering dermatologic products contain patent claims directed to the
      pharmaceutical formulation of the product. Such patents, known as formulation
      patents, are vulnerable to attacks based on the legal argument that the
      formulations covered are obvious over formulations already known prior to the
      filing of the patent application. Because obviousness is an important concept in
      patent law, recent court cases concerning obviousness and formulation patents
      were examined and discussed below. Courts have ruled that patent claims are
      obvious when features of the claimed formulation are found in the prior art, even
      if the features or characteristics of the formulation are not explicitly
      disclosed in the prior art. However, patentees have successfully overcome
      obviousness challenges where there were unexpected results or properties and/or
      the prior art taught away from the claimed invention. 

PMID- 24309314
TI  - Effect of duration and amplitude of direct current when lidocaine is delivered by
      iontophoresis.
AB  - Dosage for the galvanic stimulation for iontophoresis varies. Clinicians
      manipulate the duration or the amplitude of the current, but it is not known
      which is more effective. We compared the anesthetic effect of lidocaine HCL (2%)
      by manipulating the current parameters on 21 healthy volunteers (age: 21.2 +/-
      4.2, height 170.7 +/- 10.2 cm, mass 82.1 +/- 19.2 kg). Three conditions were
      administered in a random order using a Phoresor II(r) with 2 mL, 2% lidocaine HCL
      in an iontophoresis electrode. (1) HASD (40 mA*min): High amplitude (4 mA), short
      duration (10 min); (2) LALD (40 mA.min): Low amplitude (2 mA), long duration (20
      min); (3) Sham condition (0 mA, 20 min). Semmes-Weinstein monofilament (SWM)
      scores were taken pre and post intervention to measure sensation changes. Two-way
      ANOVA with repeated measures was used to compare sensation. Both iontophoresis
      treatments: LALD (4.2 +/- 0.32 mm) and HASD (4.2 +/- 0.52 mm) significantly
      increased SWM scores, indicating an increase in anesthesia, compared to the sham
      condition (3.6 +/- 0.06 mm) p < 0.05. Neither LALD nor HASD was more effective
      and there was no difference in anesthesia with the sham. Lidocaine delivered via
      iontophoresis reduces cutaneous sensation. However, there was no benefit in
      either a HASD or LALD treatment. 

PMID- 24309316
TI  - Formulation and in Vitro, ex Vivo and in Vivo Evaluation of Elastic Liposomes for
      Transdermal Delivery of Ketorolac Tromethamine.
AB  - The objective of the current study was to formulate ketorolac tromethamine-loaded
      elastic liposomes and evaluate their in vitro drug release and their ex vivo and
      in vivo transdermal delivery. Ketorolac tromethamine (KT), which is a potent
      analgesic, was formulated in elastic liposomes using Tween 80 as an edge
      activator. The elastic vesicles were prepared by film hydration after optimizing
      the sonication time and number of extrusions. The vesicles exhibited an
      entrapment efficiency of 73 +/- 11%, vesicle size of 127.8 +/- 3.4 nm and a zeta
      potential of -12 mV. In vitro drug release was analyzed from liposomes and an
      aqueous solution, using Franz diffusion cells and a cellophane dialysis membrane
      with molecular weight cut-off of 8000 Da. Ex vivo permeation of KT across pig ear
      skin was studied using a Franz diffusion cell, with phosphate buffer (pH 7.4) at
      32  degrees C as receptor solution. An in vivo drug permeation study was
      conducted on healthy human volunteers using a tape-stripping technique. The in
      vitro results showed (i) a delayed release when KT was included in elastic
      liposomes, compared to an aqueous solution of the drug; (ii) a flux of 0.278
      mg/cm2h and a lag time of about 10 h for ex vivo permeation studies, which may
      indicate that KT remains in the skin (with the possibility of exerting a local
      effect) before reaching the receptor medium; (iii) a good correlation between the
      total amount permeated, the penetration distance (both determined by tape
      stripping) and transepidermal water loss (TEWL) measured during the in vivo
      permeation studies. Elastic liposomes have the potential to transport the drug
      through the skin, keep their size and drug charge, and release the drug into deep
      skin layers. Therefore, elastic liposomes hold promise for the effective topical
      delivery of KT. 

PMID- 24309315
TI  - Ionic channels as targets for drug design: a review on computational methods.
AB  - Ion channels are involved in a broad range of physiological and pathological
      processes. The implications of ion channels in a variety of diseases, including
      diabetes, epilepsy, hypertension, cancer and even chronic pain, have signaled
      them as pivotal drug targets. Thus far, drugs targeting ion channels were
      developed without detailed knowledge of the molecular interactions between the
      lead compounds and the target channels. In recent years, however, the emergence
      of high-resolution structures for a plethora of ion channels paves the way for
      computer-assisted drug design. Currently, available functional and structural
      data provide an attractive platform to generate models that combine substrate
      based and protein-based approaches. In silico approaches include homology
      modeling, quantitative structure-activity relationships, virtual ligand
      screening, similarity and pharmacophore searching, data mining, and data analysis
      tools. These strategies have been frequently used in the discovery and
      optimization of novel molecules with enhanced affinity and specificity for the
      selected therapeutic targets. In this review we summarize recent applications of
      in silico methods that are being used for the development of ion channel drugs. 

PMID- 24309317
TI  - Timing vocal behaviour: experimental evidence for song overlap avoidance in
      Eurasian wrens.
AB  - Timing during vocal interactions can play a significant role in terms of
      audibility as signal overlap may lead to masking of acoustic details for both of
      the interacting animals as well as for third-party eavesdroppers. Here we
      investigated timing aspects experimentally in Eurasian wrens (Troglodytes
      troglodytes) using non-interactive playback. We applied a randomized overlay
      method incorporating the temporal pattern of singing by the focal bird to
      establish a null model and to test observed patterns of overlap against this null
      model. We used different stimulus song rates but temporal response patterns
      always resulted in significantly lower levels of overlap than expected by chance.
      The male wrens avoided overlapping by timing their song starts predominately
      right after the end of stimulus songs, but they did not avoid being overlapped by
      the stimulus songs. The territorial males typically raised their song rates
      during and after playback with a tendency to shorten between-song intervals while
      keeping song durations unchanged. Higher song rates of the playback stimuli
      increased the extent to which responders were being overlapped by the stimulus
      songs. Our data provide experimental evidence for a timing ability in Eurasian
      wrens by which they reduce mutual interference during vocal interactions. 

PMID- 24309318
TI  - Comparison of Bovine coronavirus-specific and Bovine respiratory syncytial virus
      specific antibodies in serum versus milk samples detected by enzyme-linked
      immunosorbent assay.
AB  - Bovine coronavirus (BCV; Betacoronavirus 1) and Bovine respiratory syncytial
      virus (BRSV) are significant causes of enteric and respiratory disease in beef
      and dairy cattle throughout the world. Indirect enzyme-linked immunosorbent
      assays are widely used to detect serum antibodies for herd monitoring and
      prevalence studies. In dairy herds, milk is more readily collected than serum.
      Hence, in order to investigate the test agreement between serum and milk, both
      serum and milk samples from 105 cows in 27 dairy herds were analyzed in parallel
      for presence of immunoglobulin G antibodies to BCV and BRSV. The Bland-Altman
      analyses of data demonstrated good agreement between serum and milk antibody
      titers for both viruses. The results indicate milk samples are sufficient for
      surveillance of antibodies to BCV and BRSV. 

PMID- 24309312
TI  - Pharmacokinetic drug interactions of antimicrobial drugs: a systematic review on
      oxazolidinones, rifamycines, macrolides, fluoroquinolones, and Beta-lactams.
AB  - Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug
      interactions. These drug interactions are a major concern in clinical practice as
      they may have an effect on efficacy and toxicity. This article provides an
      overview of all published pharmacokinetic studies on drug interactions of the
      commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides,
      fluoroquinolones, and beta-lactams, focusing on systematic research. We describe
      drug-food and drug-drug interaction studies in humans, affecting antimicrobial
      drugs as well as concomitantly administered drugs. Since knowledge about
      mechanisms is of paramount importance for adequate management of drug
      interactions, the most plausible underlying mechanism of the drug interaction is
      provided when available. This overview can be used in daily practice to support
      the management of pharmacokinetic drug interactions of antimicrobial drugs. 

PMID- 24309319
TI  - Heterotopic tracheal transplantation animal model of bronchiolitis obliterans: a
      reproducible model.
AB  - BACKGROUND: Chronic rejection or bronchiolitis obliterans (BO) is the main cause
      of morbidity and mortality 1 year after lung transplantation. The objective of
      this study was to develop a reproducible animal model that mimics the typical
      histological findings in human BO after lung transplantation. MATERIAL AND
      METHODS: We used 2 rat strains - Lewis (L) and Wistar (W) - and transplanted a
      segment of donor trachea into each recipient. The animals were divided into 2
      groups: 1) donor and recipient of the same strain (W-W), and 2) donor and
      recipient of different strains (L-W). From each group, we created 4 subgroups
      examined at different time-points after transplantation (7, 14, 21, and 28 days).
      Variables were: degree of narrowing of the tracheal lumen, histological findings
      classified into 1 of 5 patterns, location of the ink (green or black), and
      presence of foreign body granuloma. RESULTS: In the W-W group, we observed a
      gradual onset of fibrosis, notable at 21 and 28 days post-implant. In the L-W
      group, obliteration of the tracheal lumen was observed in all animals, with acute
      inflammation by day 7, and fibrosis from then on, loose fibrosis by day 14, and
      frank fibrosis on days 21 and 28. Green ink was observed in vascular structures,
      located in granulation tissue in the early phases of the BO-type lesion, then the
      staining becoming less clear as the histological features developed towards frank
      fibrosis. This trend was seen in both groups. CONCLUSIONS: The obliteration and
      fibrosis are more extensive if the donor and recipient are from different strains
      (L-W). Histological findings in the L-W group corresponded to progressive
      fibrosis until day 21.

PMID- 24309320
TI  - Conserved-residue mutations in Wzy affect O-antigen polymerization and Wzz
      mediated chain-length regulation in Pseudomonas aeruginosa PAO1.
AB  - O antigen (O-Ag) in many bacteria is synthesized via the Wzx/Wzy-dependent
      pathway in which Wzy polymerizes lipid-linked O-Ag subunits to modal lengths
      regulated by Wzz. Characterization of 83 site-directed mutants of Wzy from
      Pseudomonas aeruginosa PAO1 (WzyPa) in topologically-mapped periplasmic (PL) and
      cytoplasmic loops (CL) verified the functional importance of PL3 and PL5, with
      the former shown to require overall cationic properties. Essential Arg residues
      in the RX10G motifs of PL3 and PL5 were found to be conserved in putative
      homologues of WzyPa, as was the overall sequence homology between these two
      periplasmic loops in each protein. Amino acid substitutions in CL6 were found to
      alter Wzz-mediated O-antigen modality, with evidence suggesting that these
      changes may perturb the C-terminal WzyPa tertiary structure. Together, these data
      suggest that the catch-and-release mechanism of O-Ag polymerization is widespread
      among bacteria and that regulation of polymer length is affected by interaction
      of Wzz with Wzy. 

PMID- 24309321
TI  - What does the Affordable Care Act mean for Medicaid?

PMID- 24309323
TI  - Frequent CCNE1 amplification in endometrial intraepithelial carcinoma and uterine
      serous carcinoma.
AB  - Uterine serous carcinoma accounts for only 10% of all uterine epithelial cancers,
      but is the leading cause of death among them. The pathogenesis of this aggressive
      neoplasm has been largely elusive until recently, when comprehensive genome-wide
      analyses of uterine serous carcinoma have been performed. Among amplified cancer
      related genes, CCNE1, encoding for cyclin E1, is frequently amplified in uterine
      serous carcinoma. In the current study we applied fluorescence in situ
      hybridization (FISH) to determine CCNE1 copy number in uterine serous carcinoma
      and concurrent endometrial intraepithelial carcinoma, the noninvasive component
      of uterine serous carcinoma, and the results were correlated with
      clinicopathological and molecular features. We found that 20 (45%) of 44 uterine
      serous carcinomas and 11 (41%) of 27 endometrial intraepithelial carcinomas
      showed CCNE1 amplification. Overall, we found high concordance in CCNE1 copy
      number in concurrent uterine serous carcinoma and endometrial intraepithelial
      carcinoma pairs (P-value=0.0003). No correlation was observed between CCNE1 copy
      number and clinicopathological features, as well as common mutations previously
      reported in uterine serous carcinoma. In summary, we confirm that amplification
      of CCNE1 is a frequent molecular genetic change in uterine serous carcinoma.
      Moreover, the identification of CCNE1 amplification in many endometrial
      intraepithelial carcinomas suggests that this genetic event occurs early during
      tumor progression.

PMID- 24309322
TI  - Differential survival trends of stage II colorectal cancer patients relate to
      promoter methylation status of PCDH10, SPARC, and UCHL1.
AB  - Surgical excision of colorectal cancer at early clinical stages is highly
      effective, but 20-30% of patients relapse. Therefore, it is of clinical relevance
      to identify patients at high risk for recurrence, who would benefit from adjuvant
      chemotherapy. The objective of this study was to identify prognostic and/or
      predictive methylation markers in stage II colorectal cancer patients. Therefore,
      we selected six gene promoters (FZD9, PCDH10 (protocadherin 10), SFRP2, SPARC
      (secreted protein acidic and rich in cysteine), UCHL1 (ubiquitin carboxyl
      terminal hydrolase 1), and WIF1) for methylation analysis in formalin-fixed,
      paraffin-embedded primary tumor samples of colorectal cancer patients (n=143) who
      were enrolled in a prospective randomized phase III trial of the Austrian Breast
      and Colorectal cancer Study Group. Patients were randomized to adjuvant
      chemotherapy with 5-fluorouracil and leucovorin or surveillance only. Survival
      analyses revealed that combined evaluation of three promoters (PCDH10, SPARC, and
      UCHL1) showed differential effects with regard to disease-free survival and
      overall survival in the two treatment groups (significance level 0.007). In the
      chemotherapy arm, a statistically insignificant trend for patients without
      methylation toward longer survival was observed (P=0.069 for disease-free
      survival and P=0.139 for overall survival). Contrary, patients in the
      surveillance arm without methylation in their gene promoters had shorter disease
      free survival and overall survival (P=0.031 for disease-free survival and P=0.003
      for overall survival), indicating a prognostic effect of methylation in this
      group (test for interaction, P=0.006 for disease-free survival and P=0.018 for
      overall survival). These results indicate that promoter methylation status of
      PCDH10, SPARC, and UCHL1 may be used both as prognostic and predictive molecular
      marker for colorectal cancer patients and, therefore, may facilitate treatment
      decisions for stage II colorectal cancer. 

PMID- 24309324
TI  - Improved computer-assisted analysis of the global lymphatic network in human
      cervical tissues.
AB  - Lymphatic dissemination is a key event in cervical cancer progression and related
      tumor lymphatic markers are viewed as promising prognostic factor of nodal
      extension. However, validating such parameters requires an objective
      characterization of the lymphatic vasculature. Here, we performed a global
      analysis of the lymphatic network using a new computerized method applied on
      whole uterine cervical digital images. Sixty-eight cases of cervical neoplasia
      (12 CIN3, 10 FIGO stage 1A and 46 stage IB1) and 10 cases of normal cervical
      tissue were reacted with antibodies raised against D2-40, D2-40/p16 and D2
      40/Ki67. Immunostained structures were automatically detected on whole slides.
      The lymphatic vessel density (D2-40), proliferating lymphatic vessel density (D2
      40/ki67) and spatial lymphatic distribution in respect to the adjacent epithelium
      were assessed from normal cervix to early cervical cancer and correlated with
      lymphovascular space invasion and lymph node status. Prominent lymphatic vessel
      density and proliferating lymphatic vessel density are detected under the
      transformation zone of benign cervix and no further increase is noted during
      cancer progression. Notably, a shift of lymphatic vessel distribution toward the
      neoplastic edges is detected. In IB1 cervical cancer, although intra- and
      peritumoral lymphatic vessel density are neither correlated with lymphovascular
      space invasion nor with lymph node metastasis, a specific spatial distribution
      with more lymphatic vessels in the vicinity of tumor edges is predictive of
      lymphatic dissemination. Herein, we provide a new computerized method suitable
      for an innovative detailed analysis of the lymphatic network. We show that the
      transformation zone of the benign cervix acts as a baseline lymphangiogenic niche
      before the initiation of neoplastic process. During cancer progression, this
      specific microenvironment is maintained with lymphatic vessels even in closer
      vicinity to tumor cells. 

PMID- 24309326
TI  - Mullerian precursor lesions in serous ovarian cancer patients: using the SEE-Fim
      and SEE-End protocol.
AB  - Serous ovarian cancer is suggested to develop from epithelium embryologically
      derived from the Mullerian ducts. The aim of the current study is to thoroughly,
      analyze the epithelium derived from the Mullerian ducts (cervix, endometrium and
      fallopian tubes) in serous ovarian cancer patients. Sixty women diagnosed with
      serous ovarian carcinoma were included in this multicentre, observational study.
      Tissues were embedded completely for histological assessment, in accordance with
      the SEE-Fim and SEE-End protocol (Sectioning and Extensively Examining of the
      Fimbriated end; and-Endometrium), and prevalence of cervical, as well as
      endometrial and tubal pathology was analyzed. In 31 (52%) cases, a pathologic
      lesion was identified, and in 16 (27%) of these cases coexistence of pathologic
      lesions. In 1 case, severe dysplasia was found in the cervix, in 9 (15%) cases
      endometrial intraepithelial carcinoma, in 19 (32%) cases atypical hyperplasia,
      and in 23 (43%) cases serous tubal intraepithelial carcinoma. Serous tubal
      intraepithelial carcinoma was seen significantly more often concurrent with
      endometrial atypical hyperplasia or endometrial intraepithelial carcinoma than
      with benign endometrium (64 vs 28%; P=0.01). To conclude, histological assessment
      of epithelium derived from Mullerian ducts of serous ovarian cancer patients
      resulted in the identification of endometrial intraepithelial carcinoma, serous
      tubal intraepithelial carcinoma and/or endometrial atypical hyperplasia in more
      than half of cases. Coexistence of these pathologic lesions was common, and might
      represent an effect of field carcinogenesis or tumor implantation of migrating
      cells.

PMID- 24309325
TI  - Uterine smooth muscle tumors with features suggesting fumarate hydratase
      aberration: detailed morphologic analysis and correlation with S-(2-succino)
      cysteine immunohistochemistry.
AB  - Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic
      aberration due to a somatic fumarate hydratase mutation. Germline mutations
      account for the hereditary leiomyomatosis and renal cell carcinoma syndrome,
      which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell
      carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected
      cells with formation of S-(2-succino)-cysteine, which can be detected with the
      polyclonal antibody. High levels of these modified cysteine residues are found
      characteristically in fumarate hydratase-deficient cells but not in normal
      tissues or tumors unassociated with hereditary leiomyomatosis and renal cell
      carcinoma syndrome. We hypothesized that S-(2-succino)-cysteine-positive
      leiomyomas, indicating fumarate hydratase aberration, have morphologic features
      that differ from those without S-(2-succino)-cysteine positivity. Hematoxylin and
      eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed
      for features suggesting hereditary leiomyomatosis and renal cell carcinoma
      syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos,
      yielding nine cases. Germline genetic testing for fumarate hydratase mutations
      was performed in three cases. A detailed morphological analysis was undertaken,
      and S-(2-succino)-cysteine immunohistochemical analysis was performed with
      controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and
      endometrial stromal tumors (15)). Of the nine study cases, four had multiple
      uterine smooth muscle tumors. All cases had increased cellularity, staghorn
      vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion
      like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse
      granular cytoplasmic labeling with the S-(2-succino)-cysteine antibody. Two of
      three tested patients had germline fumarate hydratase mutations. Only one
      leiomyoma from the tissue microarray controls was immunohistochemically positive,
      and it showed features similar to other immunohistochemically positive cases.
      Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological
      reproducibility across cases and S-(2-succino)-cysteine immuno-positivity.
      Although the features described are not specific for the germline fumarate
      hydratase mutation or the hereditary leiomyomatosis and renal cell carcinoma
      syndrome, their presence should suggest fumarate hydratase aberration.
      Identifying these cases is an important step in the diagnostic workup of patients
      with possible hereditary leiomyomatosis and renal cell carcinoma.

PMID- 24309328
TI  - BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary
      tract cancer and restriction to intrahepatic cholangiocarcinoma.
AB  - BRAF mutations have emerged as an important predictive biomarker for metastasized
      melanoma. Other types of cancer may also benefit from BRAF mutation-targeted
      therapies. In biliary tract cancer, reported BRAF mutation rates are highly
      controversial, ranging from 0 to 33% in adenocarcinoma of the gallbladder and 0
      to 22% in cholangiocarcinoma. We here analyzed tissue microarrays of a large
      cohort of biliary tract cancer (n=377) including 159 intrahepatic
      cholangiocarcinomas, 149 extrahepatic cholangiocarcinomas, and 69 adenocarcinomas
      of the gallbladder for BRAF V600E mutation using a highly sensitive
      immunohistochemical screening approach implementing the BRAF V600E protein
      specific antibody VE1. All VE1-positive cases as well as 42 VE1-negative cases
      were additionally analyzed by Sanger sequencing. In total, only 5 VE1-positive
      cases were detected (5/377; 1%). BRAF V600E mutation was confirmed by direct
      sequencing in all cases. All 5 mutated cases were intrahepatic
      cholangiocarcinomas (5/159; 3%). None of the extrahepatic cholangiocarcinomas and
      adenocarcinomas of the gallbladder were VE1 positive. Apart from the subtype
      restriction of BRAF V600E mutation to intrahepatic cholangiocarcinoma and a
      female predominance (4 female, 1 male), no significant correlation with
      clinicopathological data and patient outcome was detected. In conclusion, we
      demonstrate that BRAF V600E mutation is a rare event in biliary tract cancer,
      accounting for only 1% of all subtypes, and is restricted to intrahepatic
      cholangiocarcinoma. In addition, we demonstrate that VE1 immunohistochemistry is
      a feasible approach to routinely screen for BRAF V600E mutation in biliary tract
      cancer patients, thereby facilitating the detection of rare patients who may
      benefit from BRAF mutation-targeted therapies.

PMID- 24309327
TI  - Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of
      fusion subtype, age, and stage.
AB  - Xp11 translocation renal cell carcinomas harbor chromosome translocations
      involving the Xp11 breakpoint, resulting in gene fusions involving the TFE3 gene.
      The most common subtypes are the ASPSCR1-TFE3 renal cell carcinomas resulting
      from t(X;17)(p11;q25) translocation, and the PRCC-TFE3 renal cell carcinomas,
      resulting from t(X;1)(p11;q21) translocation. A formal clinical comparison of
      these two subtypes of Xp11 translocation renal cell carcinomas has not been
      performed. We report one new genetically confirmed Xp11 translocation renal cell
      carcinoma of each type. We also reviewed the literature for all published cases
      of ASPSCR1-TFE3 and PRCC-TFE3 renal cell carcinomas and contacted all
      corresponding authors to obtain or update the published follow-up information.
      Study of two new, unpublished cases, and review of the literature revealed that
      8/8 patients who presented with distant metastasis had ASPSCR1-TFE3 renal cell
      carcinomas, and all but one of these patients either died of disease or had
      progressive disease. Regional lymph nodes were involved by metastasis in 24 of
      the 32 ASPSCR1-TFE3 cases in which nodes were resected, compared with 5 of 14
      PRCC-TFE3 cases (P=0.02).; however, 11 of 13 evaluable patients with ASPSCR1-TFE3
      renal cell carcinomas who presented with N1M0 disease remained disease free. Two
      PRCC-TFE3 renal cell carcinomas recurred late (at 20 and 30 years, respectively).
      In multivariate analysis, only older age or advanced stage at presentation (not
      fusion subtype) predicted death. In conclusion, ASPSCR1-TFE3 renal cell
      carcinomas are more likely to present at advanced stage (particularly node
      positive disease) than are PRCC-TFE3 renal cell carcinomas. Although systemic
      metastases portend a grim prognosis, regional lymph node involvement does not, at
      least in short-term follow-up. The tendency for PRCC-TFE3 renal cell carcinomas
      to recur late warrants long-term follow-up. 

PMID- 24309329
TI  - Evaluation of fracture resistance of reattached vertical fragments bonded with
      fiber-reinforced composites: an in vitro study.
AB  - AIM: Aim of this in vitro study was to evaluate the resistance to fracture of
      vertically fractured and reattached fragments bonded with fiber-reinforced
      composites. MATERIALS AND METHODS: Root canals of 45 teeth were prepared, and the
      teeth were intentionally fractured into two separate fragments. Control groups (n
      = 15 each) consisted unfractured teeth with instrumented and obturated. Fractured
      teeth were divided into three groups (n = 15) and were attached using (1) dual
      cure resin cement (RelyX U100), (2) dual-cure resin cement and polyethylene fiber
      (Ribbond), (3) dual-cure resin cement and glass fibers (stick-net). Force was
      applied at a speed of 0.5 mm/min to the root until fracture. RESULTS AND
      STATISTICAL ANALYSIS: Group 1 (RelyX U100 group) demonstrated lowest fracture
      resistance. Group 4 (control group) showed highest fracture resistance followed
      by group 2 (Ribbond group) and group 3 (Stick-Net groups). Statistically no
      significant difference was there between groups 2, 3 and 4. CONCLUSION:
      Vertically fractured teeth can be treated by filling the root canal space with
      dual-cure adhesive resin cement or by adding polyethylene fiber or glass fiber to
      increase the fracture resistance of the reattached tooth fragments, an
      alternative to extraction.

PMID- 24309330
TI  - Assessment of acid neutralizing capacity in cola-based drinks and energy
      beverages by artificial saliva.
AB  - OBJECTIVE: To assess the pH of regular and light cola-based drinks and energy
      drinks, and examine the acid neutralizing capacity by the addition of artificial
      saliva. MATERIALS AND METHODS: Ten packages of each product purchased locally at
      different stores were evaluated. The pH was measured by a pH-electrode calibrated
      in standard buffer solutions. To assess the pH neutralizing capacity, 1 ml/min of
      artificial saliva was added until a pH of 5.5 set as a cutoff point was reached
      in the tested solution. The data were subjected to analysis of variance (ANOVA),
      at the 0.05 significance level. RESULTS: The surveyed beverages had an initial
      acidic pH, ranging between 2.3 and 3.4. The average amount of saliva required to
      raise the pH of the cola-based drinks above 5.5 ranged between 6.0 and 6.8 ml.
      Energy drinks used volumes between 11.3 and 12.5 ml; however, it was not possible
      to achieve a pH of 5.5. CONCLUSION: According to the methodology used, it was
      concluded that: (1) All beverages analyzed showed an initial acidic pH. (2) There
      was no statistical difference between the initial pH level and acid
      neutralization by the addition of artificial saliva in both regular and light
      drinks. It was not possible to reach the appropriate pH, set as the cutoff point,
      for the energy drinks.

PMID- 24309331
TI  - Assessment of 2D:4D in subjects with anteroposterior mandibular dysplasia.
AB  - OBJECTIVES: To compare 2D:4D ratio which is determined by testosterone levels
      with patients having orthognathic, retrognathic and prognathic mandibles.
      MATERIALS AND METHODS: The study was performed at Chennai, on 320 subjects of
      which, 60 subjects (32 males and 28 females) had retrognathic mandible; 55
      subjects (25 males and 30 females) had prognathic mandible and 205 subjects (98
      males and 107 females) had normal mandible. All the subjects had a normal maxilla
      and were in the age group of 18 to 25 years. 2D:4D ratio was determined using the
      photocopies of the ventral surface of right hand made with vernier calipers of
      0.01 mm accuracy. Statistical analysis was undertaken using Student's t- test,
      ANOVA test and TukeyHSD test. RESULTS: (i) Low 2D:4D is seen in subjects with
      mandibular prognathism, (ii) Among females, low 2D:4D is seen only in prognathic
      mandible. CONCLUSION: These findings highlight the fact that testosterone plays
      an important role in mandibular growth. Thus 2D:4D, a least invasive and
      reproducible procedure can be used as an early marker for mandibular progathism,
      and as a diagnostic tool in correlating the mandibular growth with causal
      relations between hormones and craniofacial development.

PMID- 24309332
TI  - Sound waves for unsound entities: an electronic search study to evaluate the
      diagnostic efficacy of ultrasonography in cysts and tumors of maxillofacial
      region.
AB  - OBJECTIVE: The purpose of this electronic search study was to evaluate the
      diagnostic efficacy of ultrasonography in cysts and tumors of maxillofacial
      region. MATERIALS AND METHODS: An electronic search was performed for articles
      published from January 1989 to august 2009. RESULTS: Only 30 publications were
      searched and 22 publications showed high level of evidence (4 review articles, 12
      clinical studies, 2 case reports, 1 quantitative analysis, 2 research articles
      and 1 preliminary report) with total of more than 2000 patients. CONCLUSION:
      Ultrasonography is a noninvasive, low cost procedure, and recommended as a
      complimentary imaging modality.

PMID- 24309333
TI  - Utilization of dental pulp DNA as diagnostic molecular marker for fertility
      detection in men.
AB  - Recent advances in DNA technology have revolutionized forensic identification
      procedures. Teeth dentin and pulp are rich sources of DNA material, which can be
      successfully extracted and it provides us with valuable information on
      individuals, systemic health including fertility status. AIM OF STUDY: The aim of
      this study was to use DNA material extracted from human teeth pulp for detection
      of fertility status of men. MATERIALS AND METHODS: Twenty extracted premolar
      teeth of systemic disease free male Saudi individuals (45 years average age) were
      collected; eight of them were infertile while others were fertile and were used
      as control group. This information was concealed until the PCR analysis was
      performed. The results of recorded patient information was matched with the
      results of the DNA analysis. RESULTS: Results showed that the gene (sY83) an
      important gene of AZFa region in Y chromosome is important for male fertility. It
      was later evident that the infertile patients suffered from azoospermia, and that
      information is completely matched with our results. CONCLUSION: Using DNA
      extracted from dental pulp can be used successfully in determining fertility
      status of human which may help in an accurate personal identification specially
      in extreme circumstances.

PMID- 24309334
TI  - Antibiogram pattern of oral microflora in periodontic children of age group 6 to
      12 years: a clinicomicrobiological study.
AB  - AIM: The study was carried out to see the diversity of oral microflora and its
      antibiotic sensitivity test in children of age group 6 to 12 years was carried.
      MATERIALS AND METHODS: Total 50 patients of age group 6 to 12 years were analyzed
      for their oral microflora and then checked for the antibiotic susceptibility
      test. The samples that were collected were incubated at 37 degrees C for 48
      hours. Once dispersed samples were taken and Gram staining was done, also they
      were spread on to a number of freshly prepared agar plates and incubated to allow
      cells to form microbial colony. RESULTS: The result showed microflora common in
      all types, Gram-positive facultative anaerobic rods and cocci. In normal children
      Gram-positive facultative anaerobic and fermenting cocci were predominant where
      as in children with caries growth of microbiota that were Gram-negative and
      positive, capnophilic, motile and anaerobic rods and cocci belonging to members
      of genera S. mutans and A. actinomycetemcomitans was seen. CONCLUSION: By the
      present study it has been concluded that the number of bacteria determined by
      microscopic counts was twice as high in caries patients as in healthy sites, and
      also recommended that amoxicillin, ampicillin and amikacin are the most effective
      antibacterial drugs for the treatment of dental caries.

PMID- 24309335
TI  - Comparative analysis of colony counts of different species of oral streptococci
      in saliva of dentulous, edentulous and in those wearing partial and complete
      dentures.
AB  - OBJECTIVES: To study and compare the number of colony forming units of
      Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius,
      Streptococcus mitis and Streptococcus milleri in dentulous, edentulous and in
      those wearing partial and complete dentures by using semi-quantitative culture
      method of saliva samples with calibrated standard loop. MATERIALS: Sterile
      specimen collection bottles, Mitis salivarius agar plates, Standard loop, Candle
      jar, Incubator, Colony counter. METHODOLOGY: Study population consisted of 100
      subjects with 25 in each group, with an age range of 40 to 80 years, who were
      attending the Department of Community Dentistry and Prosthodontics at MNR Dental
      College, Sangareddy, Hyderabad. Unstimulated saliva samples were collected from
      patients and inoculated on to Mitis salivarius agar plates using calibrated
      standard loop. The plates were then incubated anaerobically at 37 degrees C for
      24 hours and left at room temperature for further 24 hours. Using a colony
      counter, the number of colonies of each species was counted. RESULTS:
      Streptococcus mutans and Streptococcus mitis predominates in the dentulous group,
      Streptococcus sanguis in complete denture group, Streptococcus salivarius in
      edentulous group and Streptococcus milleri in removable partial denture group.
      CONCLUSION: The results of our study are in accordance with the previous studies,
      which have sought to differentiate different groups of mutans streptococci using
      a simple calibrated standard loop.

PMID- 24309336
TI  - Evaluation of propofol as a general anesthetic agent for minor oral surgical
      procedure.
AB  - Nausea and vomiting following anesthesia is a distressing problem for the patient
      as it increases the recovery time, intensity of nursing care and delays
      discharge. The aim of randomized controlled single blind study is to evaluate the
      efficacy and safety of subhypnotic doses of propofol for the prevention of
      postoperative nausea and vomiting (PONV) in day care management of cases in oral
      and maxillofacial surgeries. Twenty-five patient of ASA-1 with age ranging from
      12 to 40 years were scheduled for various maxillofacial surgical cases like
      fracture, cyst enucleation, surgical removal of 3rd molar, etc. were given
      propofol at the dose of 2 to 2.5 mg/kg as induction dose and sedation was
      maintained with the dose 5 to 10 mg/min. There was no significant effect on heart
      rate, systolic and diastolic blood pressure, respiratory rate and oxygen
      saturation intraoperatively. In conclusion, a subhypnotic dose of propofol is
      fast acting, safe and easily controllable, short acting general anesthetic agent
      with rapid recovery. The study found that the PONV was significantly reduced in
      the patient with propofol, no hemodynamic derangements were noted in the
      postoperative period.

PMID- 24309337
TI  - Periodontal pathogens and respiratory diseases- evaluating their potential
      association: a clinical and microbiological study.
AB  - OBJECTIVE: To evaluate whether any potential association exists between
      respiratory diseases such as chronic obstructive pulmonary disease (COPD) and
      periodontal health status clinically and or microbiologically. MATERIALS AND
      METHODS: Fifty patients of COPD (test group) and 50 Patients without COPD
      (control group) were recruited for the study with more than 20 years of age with
      at least six natural teeth. All the patients were nonsmokers. Periodontal health
      was assessed by measuring clinical attachment loss (CAL) and gingival bleeding by
      using William's graduated periodontal probe. Microbiological evaluation was done
      by collecting sputum samples of the subjects with respiratory diseases to find
      out any periodontal pathogen in the lung fluid. RESULT AND CONCLUSION: The
      results showed that the subjects with COPD had significantly more bleeding sites
      (i.e. >20%) and had more of the clinical mean attachment loss (2.84 +/- 0.66)
      than those without COPD. On the basis of the observed results of the study, we
      can hypothesize that the risk for COPD appeared to be significantly elevated when
      attachment loss was found to be severe. CLINICAL SIGNIFICANCE: It is conceivable
      that oral interventions that improve oral health status may prove to lower the
      severity of lung infection in susceptible populations.

PMID- 24309338
TI  - Evaluation of the relationship between bruxism and premature occlusal contacts.
AB  - AIM: This study evaluates the relationship between occlusal interferences and
      premature contacts and bruxism by determining the relationship between unassisted
      and assisted nonworking interferences. MATERIALS AND METHODS: In this study, 60
      subjects (14 males and 46 females) that consisted of 30 bruxers (7 males, 23
      females) and 30 nonbruxers (7 males, 23 females) were selected after completion
      of a questionnaire based on the exclusion criteria. Occlusal interferences in the
      centric relation and eccentric movements in the two groups were evaluated and
      recorded. Data were analyzed by SPSS software (version 16) using the Chi-square
      and paired t-tests. RESULTS: The results showed a statistically significant
      relationship between bruxism and nonworking interferences (p < 0.05). There was
      no statistically significant relationship in the centric relation and other
      eccentric movements (p > 0.05). The number of assisted nonworking occlusal
      contacts was more than unassisted nonworking occlusal contacts. CONCLUSION:
      According to the results of this study, there is a relationship between certain
      types of occlusal interferences (nonworking interferences) and bruxism. Hence, it
      would be useful to examine occlusal contacts in bruxing patients to eliminate
      probable causative or contributing occlusal factors. Both assisted and unassisted
      nonworking occlusal contacts should be evaluated. CLINICAL IMPLICATION: Bruxism
      is an oral habit that consists of involuntary rhythmic or spasmodic nonfunctional
      gnashing, grinding or teeth clenching, other than chewing movements by the
      mandible. Bruxism may lead to occlusal trauma, tooth wear, fracture of the teeth
      and fillings, and hypertrophy of the masticatory muscles. Treatment of bruxism
      needs a correct diagnosis. Therefore, it is useful to determine the relationship
      between occlusal interferences and bruxism in order to prevent its development by
      adjusting for these interferences.

PMID- 24309339
TI  - Gingival microleakage of class V composite restorations with fiber inserts.
AB  - AIM: This study investigated the effect of different fiber inserts (glass and
      polyethylene), bonding agents, and resin composites on the gingival margin
      microleakage of class V composite restorations. MATERIALS AND METHODS: Sixty
      premolars were sterilized and mounted in acrylic resin bases. Class V cavities
      were prepared buccally and lingually, 1 mm below the cementoenamel junction,
      comprising 12 groups (n = 10). In the experimental groups fiber inserts were cut
      and placed at the gingival seat, while the control groups had no inserts.
      Combinations of two composite materials, Filtek-Z250 and Filtek-LS (3M-ESPE), and
      four bonding agents, Clearfil SE bond (Kuraray) (C), Scotch Bond Multipurpose (3M
      ESPE) (SB), Prime and Bond NT (Dentsply) (PB), and Filtek-LS (3M-ESPE) (LS) were
      used. Restorations were incrementally inserted and polymerized for 40s. Specimens
      were then stored in distilled water for 7 days and thermocycled for 500 cycles.
      Teeth surfaces were sealed with nail polish except for 1 mm around restoration
      margins and immersed in 2% red procion dye. Teeth were then sectioned
      buccolingually and dye penetration was assessed with five-point scale. Data were
      statistically-analyzed by Kruskal-Wallis, ANOVA and Tukey's tests (alpha = 5%).
      RESULTS: Mean microleakage scores varied from 0.40 (Groups C, C with
      polyethylene, LS, LS with polyethylene) to 1.50 (SB). CONCLUSION: Different
      bonding agents led to differences in microleakage scores where C and LS showed
      significantly lower microleakage than PB. SB had highest mean microleakage score,
      however, incorporation of fibers resulted in significant reduction in
      microleakage. CLINICAL SIGNIFICANCE: Class V resin composite restorations bonded
      with a total-etch adhesive had a significant reduction in mean microleakage
      scores when glass or polyethylene fibers were placed at the gingival cavo-surface
      margin. In contrast, for two self-etch adhesive systems, the incorporation of
      fibers had no significant effect on mean microleakage scores.

PMID- 24309340
TI  - Cleaning efficiency of anatomic endodontic technology, ProFile System and Manual
      Instrumentation in oval-shaped root canals: an in vitro study.
AB  - AIM: This in vitro study is an attempt to compare the effectiveness in cleaning
      oval shaped root canals using Anatomic Endodontic Technology (AET(r)), ProFile
      system(r) and Manual Instrumentation with K-files. METHODOLOGY: Sixty oval shaped
      single rooted maxillary and mandibular premolars with straight canals were
      divided in to three groups. The root canals were, confirmed as being oval shape
      by means of radiographs made in a buccolingual and mesiodistal direction.
      Automated canal preparation was performed using Anatomic Endodontic Technology
      (group 1) and the ProFile system(r) (group 2). Manual instrumentation (group 3)
      was performed with k-files. Irrigation was performed using alternatively 3% NaOCl
      and 17% EDTA, followed by rinsing with normal saline. The roots were split
      longitudinally into two halves and examined under a scanning electron microscope.
      The presence of debris and smear layer was recorded at distances 1, 5 and 10 mm
      from the working length using a three step scoring scale. Mean scores for debris
      and smear layer was calculated and statistically analyzed for between and within
      groups significance, using the Kruskal-Wallis nonparametric ANOVA test and
      Bonferroni's multiple comparison test. RESULTS: At 1, 5 and 10 mm levels the root
      canals prepared with AET had significantly less surface debris and smear layer on
      the canal walls as compared to canals prepared with ProFile system(r) or manual
      instrumentation. For all three groups significantly lower mean smear layer scores
      (p < 0.05) were recorded at 5 and 10 mm levels compared with the 1 mm level.
      Significantly lower mean debris scores (p < 0.05) were also recorded at 5 and 10
      mm levels for the AET group whereas no significant differences were found between
      the three levels for the ProFile system(r) and manual instrumentation groups.
      CONCLUSION: Although better instrumentation scores were obtained in canals
      prepared with AET, complete cleanliness was not achieved with any of the
      techniques and instruments investigated.

PMID- 24309341
TI  - Comparative analysis of efficacy and cleaning ability of hand and rotary devices
      for gutta-percha removal in root canal retreatment: an in vitro study.
AB  - AIM OF THE STUDY: To evaluate the efficacy and cleaning ability of Hedstrom
      files, and ProTaper retreatment instruments in removing gutta-percha from root
      canals with and without xylene as solvent. MATERIALS AND METHODS: Sixty extracted
      single rooted human teeth were selected and decoronated, straight access
      established working length determined 1 mm short of canal, chemomechanical
      preparation done and obturated with guttapercha and AH plus sealer. Samples were
      stored for 1 week in humidifier divided into four groups of 15 teeth each. *
      Group I: Hedstrom files without xylene. * Group II: Hedstrom files with xylene. *
      Group III: ProTaper retreatment instruments without xylene. * Group IV: ProTaper
      retreatment instruments with xylene. and the following criteria were assessed -
      Time taken for initial plunge of instrument into guttapercha. - Time taken for
      complete removal of gutta-percha to reach working length - Ability of H files and
      ProTaper retreatment files with/ without xylene to remove gutta-percha in
      coronal, middle and apical 1/3 of canal. The teeth were grooved in labiolingual
      cross section, observed under a steromicroscope and scored according to gutta
      percha debris left in the canal. Results were evaluated using ANOVA test and
      multiple comparisons done using Scheffe test. RESULTS: The least time to reach
      working length was found with group IV followed by groups III, II and group I
      respectively. Also the fastest way to remove maximum gutta-percha was group IV
      followed by groups III, II, and I respectively with a statistically significant
      difference among all groups. Apical 1/3 has more amount of remaining gutta-percha
      debris than middle and coronal 1/3 in all groups. The amount of gutta-percha
      debris in apical 1/3 was least in group IV followed by groups III, II and I
      respectively. DISCUSSION: The better performance of ProTaper rotary instruments
      has been attributed to their special flute design which tends to pull gutta
      percha coronally directing it toward orifice. Also the movements of engine driven
      instruments produce frictional heat which plasticises gutta-percha and aids in
      easy removal. Apical third of root canals showed more guttapercha debris compared
      to coronal and middle 1/3 and has been attributed to the greater anatomic
      variability and difficulty of instrumentation in the apical area. The existence
      of deep groves and depressions on dentine walls in this apical 1/3 make them less
      instrumented areas as it did be difficult to direct the file against the extreme
      root canal wall. CONCLUSION: The fastest technique to remove gutta-percha and the
      shortest time to reach working length was observed with ProTaper retreatment
      instruments with xylene followed by ProTaper retreatment files without xylene and
      Hedstrom files without xylene. After instrumentation for removal of gutta-percha,
      apical third was found to have more debris compared to coronal and middle 1/3 of
      the root canal.

PMID- 24309342
TI  - An in vivo evaluation of different methods of working length determination.
AB  - OBJECTIVE: The purpose of this in vivo study was to compare the ability of
      digital tactile, digital radiographic and electronic methods to determine
      reliability in locating the apical constriction. MATERIALS AND METHODS: Informed
      consent was obtained from patients scheduled for orthodontic extraction. The
      teeth were anesthetized, isolated and accessed. The canals were negotiated, pulp
      chamber and canals were irrigated and pulp was extirpated. The working length was
      then evaluated for each canal by digital tactile sensation, an electronic apex
      locator (The Root ZX) and digital radiography. The readings were then compared
      with post-extraction working length measurements. RESULTS: The percentage
      accuracy indicated that EAL method (Root ZX) shows maximum accuracy, i.e. 99.85%
      and digital tactile and digital radiographic method (DDR) showed 98.20 and 97.90%
      accuracy respectively. CLINICAL SIGNIFICANCE: Hence, it can be concluded that the
      EAL method (Root ZX) produced most reliable results for determining the accurate
      working length.

PMID- 24309343
TI  - Accuracy of electronic apex locator in enlarged root canals with different root
      canal irrigants: an in vitro study.
AB  - AIM: To evaluate the accuracy of Root ZX-II (J Morita Corp) apex locator in
      enlarged root canals with different root canal irrigants. MATERIALS AND METHODS:
      48 freshly extracted single rooted mandibular premolar teeth were used. The
      apical enlargement was done up to #45 K-file as the master apical file (MAF). The
      teeth were randomly divided into 4 groups and mounted in an experimental
      apparatus. The following irrigants were used during electronic canal
      measurements: group 1: saline; group 2: 3% NaOCl; group 3: 2% chlorhexidine;
      group 4: 17% EDTA. The canal measurement was done with Root ZX-II apex locator
      using #10 and #45 K-file. Data were analyzed by two way ANOVA and Bonferroni
      multiple comparison test. RESULTS: Statistical analysis showed that there was
      statistically significant difference between #10 and #45 K-file for group 1 (p <
      0.01). CONCLUSION: Root ZX-II was accurate in the presence of 3% NaOCl and 17%
      EDTA when measured with smaller and larger files. However, it was accurate in the
      presence of saline and 2% CHX when larger files were used.

PMID- 24309344
TI  - A scanning electron microscopic study to evaluate the efficacy of NaviTip FX in
      removing the canal debris during root canal preparation: an in vitro study.
AB  - OBJECTIVE: To evaluate the efficacy of NaviTip FX in removing the canal debris
      during root canal preparation using scanning electron microscopic study.
      MATERIALS AND METHODS: Thirty single rooted teeth with completely formed apices
      were used in this study. Standard endodontic access cavity preparations were
      performed. Then the teeth were randomly divided into two groups: groups 1 and 2
      of 15 teeth each group. For group 1, NaviTip FX (brush covered needle) was used
      to irrigate the canal with 5.25% sodium hypochlorite after each instrument use.
      For group 2, NaviTip (brushless needle) was used for irrigation following each
      instrument use. ProTaper rotary files were used for the canal preparation. The
      teeth were then cleaned and dried before splitting them into two halves. The half
      with most visible part of the apex was used for scanning electron microscopic
      evaluation. The results were statistically analyzed using the Mann-Whitney U-test
      at significance level p < 0.005. RESULTS: The mean values for coronal and middle
      third of group 1 showed lower debris scores than group 2 and this difference was
      statistically significant at a p-value 0.01 and 0.05 respectively, but no
      significance difference between them at the apical third at a p-value of < 0.05.
      CONCLUSION: The NaviTip FX (brush covered needle) showed effectively better canal
      wall debris removal than the NaviTip (brushless needle).

PMID- 24309345
TI  - Finishing and polishing procedures of composite restorations by Saudi dentists: a
      cross-sectional study.
AB  - AIM: The purpose of this study was to assess the knowledge and practices of Saudi
      dentists in finishing and polishing composite restorations. MATERIALS AND
      METHODS: A cross-sectional questionnaire-based study was conducted among 306
      Saudi dentists from March to April 2012. The collected data were analyzed using
      Microsoft Excel 2010 program and descriptive statistics were obtained. RESULTS:
      Completed questionnaires were returned by 191 participants, giving a response
      rate of 62.4%. 115 (65.7%) respondents are using fine diamond finishing burs for
      finishing occlusal surfaces, 82 (48%) used fine aluminum oxide finishing discs
      for finishing facial surfaces, 130 (76%) used diamond finishing strips for
      finishing interproximal surfaces.121 (63.4%) respondents were of the view that
      the type of filler content has a major influence in providing color stability to
      the composite restoration and 137 (72.1%) believed nano-composites provided
      enhanced color stability. CONCLUSION: Dentists in Saudi Arabia are aware of the
      benefits of proper finishing and polishing of composite restorations. They
      however need to use finishing and polishing burs, disks, strips and pastes in a
      sequential series. Usage of composite polishing pastes and composite surface
      sealants should be emphasized in undergraduate curriculum.

PMID- 24309346
TI  - Effect of different polishing systems and drinks on the color stability of resin
      composite.
AB  - AIM: The purpose of this study was to evaluate the color stability of resin
      composit using different finishing systems and drinks. MATERIALS AND METHODS:
      Composit disks (5 mm diameter, 2 mm thickness) were prepared for each nanofilled
      composite using a brass mold. The specimens were divided into 5 finishing system
      groups Mylar strip (Mylar, DuPont, Wilmington, Del., USA), Soft Lex (3M(TM)
      ESPE(TM) St. Paul, MN, USA), Enhance (Dentsply-DeTrey GmbHD Konstanz, Germany),
      Hiluster (KerrHawe, Bioggio, Switzerland), Opti Disc (KerrHawe, Bioggio,
      Switzerland) and each group was divided into 10 subgroups (n = 10) and stored for
      24 hours at 37 degrees C in different drinks water coffee, coffee with sugar,
      tea, tea with sugar, diet coke, coke, light sour cherry juice or sour cherry
      juice. Color of all specimens was measured before and after exposure with a
      spectrophotometer using CIE L*a*b* relative, and color changes (DeltaE*) were
      then calculated. The data were analyzed with a twoway analysis of variance
      (ANOVA), and mean values were compared by the Tukey HSD test (p = 0.05). RESULTS:
      For the drinks, the lowest DeltaE* values were observed in the water and highest
      DeltaE* values were observed in sour cherry juice. When drinks with and without
      sugar were compared, all groups with sugar demonstrated a higher color difference
      than without sugar. For the different finishing systems, Mylar strip group
      demonstrated significantly highest color change; Enhance groups demonstrated
      significantly lowest color change. CONCLUSION: Finishing treatments and storage
      solutions significantly affect the color stability of resin composite. The
      presence of sugar in drinks increased the color difference compared to drinks
      without composit. CLINICAL SIGNIFICANCE: Polishing techniques and drinking drinks
      with sugar may affect the color of esthetic restorations.

PMID- 24309347
TI  - Comparison of dimensional accuracy of four different die materials before and
      after disinfection of the impression: an in vitro study.
AB  - BACKGROUND: This study was conducted to compare the linear dimensional accuracy
      of die materials before and after disinfection of the impression. Type IV and V
      conventional dental stone, type IV-resin impregnated and copper-plated die
      materials were studied. MATERIALS AND METHODS: A stainless-steel master die
      analogs to a complete veneer crown preparation with three scribed lines (I:
      vertical, II and III: horizontal) was machined and measurements were made from
      these scribed reference lines. Impressions were made with monophase addition
      silicone impression material for each of the specimens. 2% glutaraldehyde was
      used as a disinfectant. The fabricated dies were measured to the nearest 0.0001
      mm. ANOVA and post hoc was carried out using Scheffe multiple comparison test at
      significance level of 0.05. RESULTS: Type IV resin-impregnated dental stone and
      copperplated dies approximated the dimensions of the master die. Type IV and V
      conventional dental stone dies showed greater variation in measurements.
      Statistically significant differences were observed for type IV resin-impregnated
      and copper-plated dies in dimension I and III. For dimension II no significant
      differences were found for dies fabricated from four die materials. A one-way
      analysis of variance indicated no statistical significant differences among the
      two groups of dies fabricated from disinfectant treated impressions and those
      fabricated from nondisinfectant treated impressions. CONCLUSION: Type IV resin
      impregnated dental stone and copper-plated dies are dimensionally more accurate
      than type IV and V conventional dental stone die materials. No significant linear
      distortion in the dies fabricated from the disinfected impressions was observed.

PMID- 24309348
TI  - Bond strength of overdenture locator posts cemented with seven luting agents.
AB  - STATEMENT OF THE PROBLEM: Post retention is crucial factor in restoration
      survival. Posts are commonly failed due to loss of retention. It is unknown which
      luting agents would provide the maximum bond strength for Locator overdenture
      posts. AIM: The aim of this study was to evaluate the bond retentive strengths of
      Locator overdenture posts cemented with 7 luting agents. MATERIALS AND METHODS:
      One hundred and five single rooted human teeth were decoronated and randomly
      assigned to 7 groups (n = 15). Post spaces were prepared with Locator post drills
      to the depth of 6 mm. The Locator posts were cemented with Variolink II, RelyX
      ARC, Multilink N, RelyX Unicem, ParaCore, or MultiCore Flow resin luting agents.
      Zinc phosphate cement was served as control group. Specimens were stored in water
      at 37 degrees C for 24 hours. Each specimen was loaded in tension in an Instron
      universal testing machine. The maximum force required to dislodge each Locator
      post was recorded. Means and standard deviations were calculated and data were
      statistically analyzed with one-way analysis of variance (ANOVA). RESULTS: The
      highest mean bond strength value for Locator posts was recorded for
      MultiCore((r)) Flow group (mean = 550.1 N), while the lowest mean value was for
      RelyX Unicem(TM) resin cement group (mean = 216.8 N). A statistically significant
      difference in mean locator overdenture post bond strength was observed between
      the 7 cement types (p < 0.0001). ParaCore(TM) and MultiCore((r)) Flow groups had
      significantly higher bond strength than all other groups, but they were not
      differed from each other. CONCLUSION: Bond strength of Locator overdenture posts
      were influenced by the type of luting agents. MultiCore Flow and ParaCore resin
      cements offered the greatest retention. CLINICAL SIGNIFICANCE: The type of luting
      agents had a significant effect on the retention of Locator posts. The use of
      Core buildup resin cements as luting agent with Locator post demonstrated the
      greatest retention.

PMID- 24309349
TI  - Color stability of restorative materials in response to Arabic coffee, Turkish
      coffee and Nescafe.
AB  - OBJECTIVE: To evaluate the effect of Arabic coffee, Turkish coffee and Nescafe on
      the color stability of four different composite resins after a period of aging
      time 1, 7 and 30 days. MATERIALS AND METHODS: Twenty specimens from each type of
      tested composite resin material were prepared. Five specimens from each tested
      material (Z350 XT, Artist, GC and Z250) was evaluated after storage in Arabic
      coffee, Turkish coffee, Nescafe and distil water (control) at 37 degrees C in a
      dark container for 1, 7 and 30 days. Color measurement was done using colorimeter
      based on the CIE L* a* b* color scale. Color differences DeltaE*ab, Deltab* and
      Deltaa* among specimens immersed in distil water and staining coffee beverages
      were evaluated overtime. Mean values were statistically analyzed with one-way
      analysis of variance (ANOVA), followed by Tukey test with p < 0.05 as
      significance level. RESULTS: All tested composite resins showed increase color
      change after a period of 1, 7 and 30 days. The color change DeltaE*ab , Deltab*
      and Deltaa* exhibited by Arabic coffee, in Turkish coffee and Nescafe except
      Deltaa*. The highest total color difference DeltaE*ab after 30 days was in group
      A Arabic coffee (DeltaE > 1.5 perceivable) and not perceivable in group B Turkish
      coffee and group C Nescafe. For Deltab* all materials discolored toward
      yellowness after 30 days except Arabic coffee group which shifted from yellowness
      toward blueness (Deltab*> 1.5 perceivable). CONCLUSION: The effect of staining
      beverages on the resin composite materials increases with time of aging toward
      yellowness and not perceivable in all groups except with Arabic coffee which had
      highest effect after 30 days and the discoloration shifted from yellowness to
      blueness perceivable.

PMID- 24309350
TI  - Influence of solvents and composition of etch-and-rinse and self-etch adhesive
      systems on the nanoleakage within the hybrid layer.
AB  - AIM: The goal of this study was to evaluate nanoleakage within the hybrid layer
      yielded by etch-and-rinse and self-etch adhesive systems, with different solvents
      and compositions. MATERIALS AND METHODS: Four adhesives were applied onto 20
      human dentin disks: group A: Adper Scotchbond 1XT(TM) (3M ESPE), group B: One
      Coat Bond((r)) (Coltene Whaledent), group C: AdheSE((r)) (Ivoclar Vivadent) and
      group D: Xeno-V((r)) (Dentsply). The samples were immersed in aqueous ammoniacal
      silver nitrate for 24 hour, prepared and observed under field-emission scanning
      electron microscopy with backscattered electrons. Microphotographs were scanned
      and data were processed. The mean value and standard deviation were calculated.
      Kruskal- Wallis and Mann-Whitney tests were used (p < 0.05). RESULTS: All the
      adhesives showed nanoleakage within the hybrid layer: Adper Scotchbond 1XT(TM)
      (218.5 um +/- 52.6 um), One Coat Bond((r)) (139.6 um +/- 79.0 um), AdheSE((r))
      (92.7 um +/- 64.8 um) and Xeno-V((r)) (251.0 um +/- 85.2 um). AdheSE((r)) yielded
      less nanoleakage than Adper Scotchbond-1XT(TM) (p = 0.003) and than Xeno-V((r))
      (p = 0.007). No other statistically significant differences were detected.
      CONCLUSION: Two-step self-etch adhesive system (AdheSE((r))) might contribute for
      lower nanoleakage deposition and thus better performance in dentin adhesion.
      CLINICAL SIGNIFICANCE: The two-step self-etch adhesive system showed the lowest
      nanoleakage deposition compared with the other adhesive systems evaluated, which
      seems to indicate a better behavior when a restoration is performed in dentin and
      possibly can lead to a durable adhesion along time.

PMID- 24309351
TI  - Shear bond strength of two adhesive materials to eroded enamel.
AB  - AIM: To evaluate the bond strength of one etch-and-rinse adhesive system and one
      resin-modified glass ionomer cement to sound and eroded enamel. MATERIALS AND
      METHODS: Forty-eight bovine incisors were embedded in acrylic resin and ground to
      obtain flat buccal enamel surfaces. Half of the specimens were submitted to
      erosion challenge with pH-cycling model (3x/cola drink for 7 days) to induce
      eroded enamel. After that, all specimens were randomly assigned according to
      adhesive material: etch-andrinse adhesive system (Adper Single Bond 2 - 3M ESPE,
      USA) or resin-modified glass ionomer cement (Vitro Fil LC - DFL, Brazil). The
      shear bond testing was performed after 24 hours water storage (0.5 mm/min). Shear
      bond strength means were analyzed by two-way ANOVA and Tukey post hoc tests (p <
      0.05). RESULTS: Adper Single Bond 2 showed the highest bond strength value to
      eroded enamel (p < 0.05), whereas no difference was observed in sound enamel
      compared with Vitro Fil LC (p > 0.05). CONCLUSION: Bond strength of etch-and
      rinse adhesive system increases in eroded enamel, while no difference is verified
      to resin-modified glass ionomer cement. CLINICAL SIGNIFICANCE: Adhesive materials
      may be used in eroded enamel without jeopardizing the bonding quality; however it
      is preferable to use etch-and-rinse adhesive system.

PMID- 24309352
TI  - Effect of energy drinks on the color stability of nanofilled composite resin.
AB  - OBJECTIVE: To study the effect of three energy drinks on the color stability of
      nanofilled composite resins after different periods of aging time. MATERIALS AND
      METHODS: Composite resin disks, 6 mm diameter, 3 mm thickness were prepared from
      Filtec Z350 XT, Tetric EvoCeram, and Filtec Z250 XT. Specimens from each material
      were tested after aging with Red Bull, Bison and Power Horse energy drinks and
      distilled water as a control. Specimens were stored at 37 degrees C in dark
      containers for 1, 7, 30 and 60 days. Color was assessed in the CIELAB using a
      colorimeter before and after each storage period. Color differences DeltaE*ab and
      Deltab* among specimens were measured. Mean values were statistically analyzed
      using one-way analysis of variance (ANOVA), with p < 0.05 as significance level.
      RESULTS: The color change DeltaE*ab and Deltab* occurred by Red Bull, Bison and
      Power Horse energy drinks was significantly different for all tested materials at
      all four times p < 0.05 except in the Red Bull group. All specimens showed
      increase in color changes toward yellowness Deltab* after a period of 1, 7, 30
      and 60 days. The highest total color difference DeltaE*ab was found in the Red
      Bull group after 60 days. CONCLUSION: Energy drinks used in this study had
      staining effect on the tested composite resin materials. The discoloration
      increased with aging time toward yellowness; however, it was not perceptible in
      all test groups after 60 days.

PMID- 24309353
TI  - Comparison of the remaining dentin thickness in the root after hand and four
      rotary instrumentation techniques: an in vitro study.
AB  - AIM: The aim of the present study was to compare the remaining dental thickness
      (RDT) in the mesiobuccal root of mandibular first molars at 3 and 7 mm from the
      anatomic apex after instrumentation with ProTaper, light speed LSX, K3 and M2 and
      to compare with that of K-files. MATERIALS AND METHODS: In this study, 60
      extracted, untreated human mandibular first molars with fully formed apices, with
      curvature less than 35 degrees  and no root resorption were used. Prepared
      specimens were cut horizontally at 3 and 7 mm short of anatomic apex. The least
      dentin thickness from canal to external root surface was observed under 3*
      magnification and recorded using Clemax measuring tool and the sections were
      reassembled. Group I-instrumentation with ProTaper, group II-instrumentation with
      K3, group III-instrumentation with Light Speed LSX, group IV-instrumentation with
      M2 and group V- instrumentation with K-files and RDT was measured. RESULTS:
      Results showed that group V removed lesser amount of dentin compared to all other
      groups while all the three instrumentation techniques removed almost equal amount
      of dentin apically. CLINICAL SIGNIFICANCE: Cleaning and shaping of the root canal
      space involves the elimination of pathogenic contents as well as attaining a
      uniform specific shape. However, the RDT following the use of various
      intraradicular procedures is an important factor to be considered as an
      iatrogenic cause that may result in root fracture. To avoid this, newer rotary
      instruments are being introduced.

PMID- 24309354
TI  - Effects of commonly consumed beverages on surface roughness and color stability
      of the nano, microhybrid and hybrid composite resins: an in vitro study.
AB  - BACKGROUND: Consumption of certain beverages may affect the esthetic and physical
      properties of the resin composite, thereby undermining the quality of
      restorations. AIM: To analyze the effect of three beverages (cola, coffee, tea)
      on color stability and surface roughness of three different types of resin
      composites at various time intervals in vitro. MATERIALS AND METHODS: Nano,
      microhybrid and hybrid resin composites were used. Each material was randomly
      divided into four equal subgroups of 10 samples each according to the beverages
      used (cola, coffee, tea, distilled water). The samples were immersed in each
      beverage for 1, 15 and 30 days. Surface roughness and color changes measurements
      were noted at the baseline-the first, fifteenth and thirteenth day. RESULTS: It
      was found that nanoresin composite followed by microhybrid and hybrid showed
      least surface roughness and color change. The Coke beverage subgroup showed more
      surface roughness and the subgroup coffee has shown more color changes with
      respect to other subgroups. CONCLUSION: All specimens showed discoloration after
      completion of the test period which was visually perceptible and clinically
      unacceptable. At the end of 30th day, among the materials, nanofilled composite
      resin showed comparatively less surface roughness and color change than
      microhybrid and hybrid composite resins.

PMID- 24309355
TI  - Prevalence of dental anomalies in Saudi orthodontic patients.
AB  - AIM: This study aimed to investigate the prevalence of dental anomalies and study
      the association of these anomalies with different types of malocclusion in a
      random sample of Saudi orthodontic patients. MATERIALS AND METHODS: Six hundred
      and two randomly selected pretreatment records including orthopantomographs
      (OPG), and study models were evaluated. The molar relationship was determined
      using pretreatment study models, and OPG were examined to investigate the
      prevalence of dental anomalies among the sample. RESULTS: The most common types
      of the investigated anomalies were: impaction followed by hypodontia,
      microdontia, macrodontia, ectopic eruption and supernumerary. No statistical
      significant correlations were observed between sex and dental anomalies. Dental
      anomalies were more commonly found in class I followed by asymmetric molar
      relation, then class II and finally class III molar relation. No malocclusion
      group had a statistically significant relation with any individual dental
      anomaly. CONCLUSION: The prevalence of dental anomalies among Saudi orthodontic
      patients was higher than the general population. CLINICAL SIGNIFICANCE: Although,
      orthodontic patients have been reported to have high rates of dental anomalies,
      orthodontists often fail to consider this. If not detected, dental anomalies can
      complicate dental and orthodontic treatment; therefore, their presence should be
      carefully investigated during orthodontic diagnosis and considered during
      treatment planning.

PMID- 24309356
TI  - The influence of different factors on the oral health status of smoking and
      nonsmoking adults.
AB  - AIM: The aim of this study to determine the influence of smoking on self-reported
      oral health status among university students. MATERIALS AND METHODS: Voluntary
      sample of 669 adults of 18 to 26 years old were invited to participate in the
      study. They were asked to read a self-designated questionnaire and a covering
      letter which explained the purpose of the study. The questionnaire addressed self
      reported demographics, oral hygiene and smoking habits; knowledge about smoking
      and its effects on oral health. Data were statistically analyzed using Chi-square
      test to determine statistically significant differences across the oral health
      status. RESULTS: The sample included 340 (56.7%) males and 240 (43.3%) females;
      56.8% of the subjects were nonsmokers; 43.2% were current smokers, and 17.5%
      smoke argileh. Almost 24.7% of subjects started smoking because of emotional
      effects; 66.9% did not smoke because of its harm to health. The percentage of
      subjects with dental plaque on their teeth was 27.1%, and with calculus was
      27.9%, and with stains was 26.9%. About 35.5% of the subjects brushed their teeth
      once daily. Statistically, significant association was proven between smoking and
      gender (p < 0.01); and smoking and halitosis (p < 0.01). CONCLUSION: Smoking is
      significantly related to esthetics, calculus, tooth stains, halitosis, gingival
      bleeding, and gender with p < 0.01, p < 0.01, p < 0.01, p < 0.01, p = 0.05, and p
      < 0.01 respectively.

PMID- 24309357
TI  - Long-term evaluation of clinical performance of direct-bonded brackets: an
      epidemiologic survey.
AB  - AIM: The objective of the current epidemiologic study was to investigate
      characteristics associated with bracket failure in bonded brackets. MATERIALS AND
      METHODS: A retrospective study on data of 144 patients treated during 2009 to
      2012 was done. Baseline data including age, gender, malocclusion, bite type and
      debonding incidences per teeth were retrieved. ANOVA analysis and t-test were
      used to evaluate the data. RESULTS: Second premolar teeth had significantly
      higher debonding incidences. Patients' age was negatively correlated with
      debonding incidences. No difference was observed for various types of
      malocclusion (class I, II and III), arch side (right or left) or arch location
      (upper or lower). However, deep bite patients had significantly higher failure
      incidents. CONCLUSION: For a total of 144 patients with 2,524 bonded brackets,
      the overall failure rate was 7.8%. Deep bite was the only factor that was
      associated with higher bracket failure. The bracket failure incidents tend to
      decrease as patients age increase. CLINICAL SIGNIFICANCE: Deep bite patients and
      also second premolar teeth seem to be especially prone to debonding incidents.
      Care must be taken to avoid premature contacts in deep bite patients. Also strict
      adherence to moisture control protocols when bonding second premolar teeth is
      recommended since these teeth are at increased risk for debonding.

PMID- 24309358
TI  - Prevalence of dental caries and oral hygiene status among school going children:
      an epidemiological study.
AB  - Oral health is an important part of general health of body. Oral hygiene
      determines oral health status. Thus, oral hygiene is most important for good
      health in general. Poor oral hygiene can be source of many diseases. By
      maintaining the good oral hygiene, we can prevent occurrence of many disease. A
      survey was carried out to assess oral hygiene status and to find out caries
      prevalence rate among school going children of age 6 to 12 years. 957 healthy
      subjects including 567 boys and 390 girls from four different schools were
      examined in broad day light with the help of mouth mirror and explorer.

PMID- 24309359
TI  - Dental health and treatment needs among children in a tribal community.
AB  - OBJECTIVE: To assess the dental health status and treatment needs among children
      of 'Pardhi' tribal community. METHODS: A total of 185 children were examined over
      a period of 2 months using WHO proforma. The statistical software namely SPSS
      version 15.0 and data was analyzed using Student's t-test and ANOVA test at p <
      0.05. RESULTS: The mean score for dft and DMFT was 1.87 +/- 1.073 and 2.04 +/-
      1.564 respectively with males subjects were having comparatively more scores. It
      was also found significant differences between age groups. Most of the children
      needed one surface filling, i.e. 29.40%, followed by pulp care and restoration
      (19.30%), two or more surface fillings (15.60%) and extraction (11.70%). CLINICAL
      SIGNIFICANCE: The study subjects were characterized by a lack of dental care
      services, high prevalence of dental caries and treatment needs. Therefore,
      implementation of a basic oral health care program for this tribal population is
      a high priority.

PMID- 24309360
TI  - Secondary closure of alveolar clefts with mandibular symphyseal bone grafts and
      with platelet-rich fibrin under local anesthesia: three case reports.
AB  - Secondary alveolar bone grafting is a method that enables an excellent oral
      rehabilitation of the patients having cleft palate. Many types of bone grafts
      have been used for reconstruction of the cleft, including autogenous bone and
      bone substitutes. Platelet-rich fibrin (PRF) has been shown to be effective in
      grafting the defect. The aim of this presentation is to report the closure of an
      alveolar cleft with the use of symphyseal bone grafts harvested with platelet
      rich fibrin under local anesthesia. PRF may be a good treatment choice depending
      on the early radiographical view of the defect and uneventfull healing.

PMID- 24309361
TI  - Advancing mandibular swelling: a diagnostic dilemma.
AB  - Asymmetrical swelling of the mandible in adolescence may pose a significant
      diagnostic dilemma. The differential diagnosis ranges from traumatic, infectious,
      and metabolic processes to benign and malignant tumors. Also may present with
      similar clinical and radiological features, making an accurate diagnosis quite
      difficult. This is an illustrative case involving a 30-year-old female who
      initially presented with complaint of pain and swelling in the lower left side of
      the face for 2 months. Multiple investigations and several biopsies were required
      to arrive at a diagnosis. This paper deals with a case report of a fibrosarcoma
      involving the mandible highlighting the importance of early diagnosis and
      treatment planning.

PMID- 24309362
TI  - Endoscopic retrieval of dental implant from maxillary sinus.
AB  - AIM: Minimally invasive method for retrieving displaced objects like implants
      from the maxillary antrum with minimal complications. BACKGROUND: Minimal
      invasive endoscopic surgery has been developed for various indications in the
      craniomaxillofacial area. CASE DESCRIPTION: In this article, a technique for
      endoscopic removal of a dental implant displaced into the maxillary sinus is
      presented. Access to the implant was achieved transorally via the canine fossa.
      The endoscopic surgical approach described was reliable and minimally invasive
      for removing dental materials displaced into the maxillary sinus. CONCLUSION:
      Transantral endoscopic surgery is a reliable, minimally invasive method for
      retrieving displaced objects from the maxillary antrum with minimal
      complications.

PMID- 24309363
TI  - Intraoral manifestations in a patient with Epidermal nevus syndrome.
AB  - AIM: To report rare findings of oral and periodontal manifestations in a patient
      with Epidermal nevus syndrome (ENS). BACKGROUND: The ENS describes the rare
      association of an epidermal nevus with abnormalities of central nervous
      system,ocular and skeletal abnormalities. Reports of oral involvement have been
      few. Also, most of the intraoral lesions have been reported in patients with nevi
      that do not fulfill the criteria for the diagnosis of ENS. CASE DESCRIPTION: This
      report describes a case of ENS that, in addition to cutaneous manifestations
      showed skeletal involvement and intraoral manifestations such as the extension of
      the nevi on the face intraorally involving the labial mucosa, hypoplasia,
      hypodontia of teeth and severe periodontal destruction. CONCLUSION: Patients with
      extensive epidermal nevi and systemic abnormalities should be suspected of having
      the ENS. Evaluation and management of patients with ENS requires a
      multidisciplinary team approach involving the dermatologist, pediatrician,
      ophthalmologist, neurologist, genetist, plastic surgeon and orthopedic services.
      Although uncommonly described in association with ENS, significant intraoral
      lesions do occur. Periodontal manifestations as in our patient, which to our
      knowledge has not been described in association with ENS so far, may also be
      present. CLINICAL RELEVANCE: Alteration of the response of periodontal tissues to
      dental plaque in the presence of certain systemic diseases has been reported, but
      not in association with ENS. Severe periodontal destruction due to exaggerated
      response to dental plaque was seen in the present case. Hence, emphasis on oral
      hygiene maintenance in such patients is essential. Patients with ENS must be
      evaluated periodically as they show a persistent predisposition for the
      development of tumors.

PMID- 24309364
TI  - Going green with eco-friendly dentistry.
AB  - Eco-friendly dentistry is currently transforming the medical and dental field to
      decrease its affect on our natural environment and reduce the amount of waste
      being produced. Eco-friendly dentistry uses a sustainable approach to encourage
      dentists to implement new strategies to try and reduce the energy being consumed
      and the large amount of waste being produced by the industry. Many reasonable,
      practical and easy alternatives do exist which would reduce the environmental
      footprint of a dental office were it to follow the 'green' recommendations.
      Dentist should take a leading role in the society by implementing 'green'
      initiatives to lessen their impact on the environment. This article provides a
      series of 'green' recommendations that dentists around the world can implement to
      become a leading Stewards of the environment.

PMID- 24309365
TI  - The museum maze in oral pathology demystified-part I.
AB  - Museum technologies provide a wide array of choice of museums to those who wish
      to exploit technology to attract, excite and ensure an unrivalled visitor
      experience, as well as capture and sustain share of mind and heart. Museum being
      a combination of both art and science requires skilled workmanship, meticulous
      planning and execution to exhibit a specimen to its optimal elegance due to its
      relatively smaller size and fragile nature. A well established oral pathology
      museum is rarely seen due to negligence of oral specimens, dearth of knowledge in
      this field and also available data on it. An insight on oral pathology museum,
      including its establishment, importance and advanced technologies to make it more
      simple and accessible are discussed in two parts. Part I emphasizes on basics in
      oral pathology museum, whereas part II highlights the specialized techniques and
      recent advances in museum technology. Our effort is to present this article as
      hands on experience for the pathologists, student population and the technicians.

PMID- 24309366
TI  - Carrier-based root canal filling materials: a literature review.
AB  - A review of the literature on the use of carrier based obturation materials
      focusing on Thermafil and Resilon based obturator (RealSeal 1) are presented in
      this article. The review addressed the history, apical leakage, coronal leakage,
      biocompatibility, sealing ability and clinical success of Thermafil and RealSeal
      1. Based on the studies gathered, this review concluded that both treatment
      techniques (Thermafil and RealSeal 1) did not provide excellent apical sealing
      ability. More research should be done to try to overcome their main drawback, its
      sealing ability.

PMID- 24309367
TI  - The evolution of tooth whitening.

PMID- 24309369
TI  - Chemotherapy for small-cell lung cancer.

PMID- 24309368
TI  - Clinical characteristics of non-small cell lung cancer patients who experienced
      acquired resistance during gefitinib treatment.
AB  - BACKGROUND: The NSCLC patients who experienced good clinical responses to an EGFR
      TKI will inevitably develop acquired resistance. A great deal of research is
      being carried out to discover the molecular mechanisms underlying this
      resistance. In comparison, few studies have been conducted to find out about the
      clinical characteristics of acquired resistance in the patients who had responded
      to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLC patients
      who experienced acquired resistance during gefitinib therapy. PATIENTS AND
      METHODS: We reviewed NSCLC patients who showed a clinical benefit from initial
      gefitinib therapy. All clinical data were obtained from 11 centers of Korean
      Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired
      resistance, time to progression (TTP), and post-progression survival (PPS) after
      gefitinib failure were analyzed retrospectively. RESULTS: A total of 417 patients
      were recruited. Median TTP was 10.2 months (95% CI, 9.5-10.9). TTP showed a
      significant longer duration in female, non-smoker, and patients with
      adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed
      symptomatic deterioration. Sites of disease progression were as follows: primary
      lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%.
      Patients with EGFR wild type showed a tendency of higher frequency in symptomatic
      deterioration and newly development of CNS metastasis compared with patients with
      EGFR mutation. There was a significant difference in newly development of lung
      metastasis between patients with exon 19 deletion and those with L858R mutation
      (41.4% vs. 6.3%, p=0.02). PPS was 8.9 months (95% CI, 7.4-10.4). Smoking history,
      PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS.
      CONCLUSION: This study suggests that clinical manifestations of acquired
      resistance may be different according to EGFR mutation status and EGFR mutation
      genotype. In addition, subsequent chemotherapy confers clinical benefit in terms
      of PPS in NSCLC patients who experienced acquired resistance after gefitinib
      therapy.

PMID- 24309370
TI  - Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited
      stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent
      accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised
      phase 3 study.
AB  - BACKGROUND: Four cycles of etoposide plus cisplatin and accelerated
      hyperfractionated thoracic radiotherapy (AHTRT) is the standard of care for
      limited-stage small-cell lung cancer (SCLC). Irinotecan plus cisplatin
      significantly improved overall survival compared with etoposide plus cisplatin
      for extensive-stage SCLC. We compared these regimens for overall survival of
      patients with limited-stage SCLC. METHODS: We did this phase 3 study in 36
      institutions in Japan. Eligibility criteria included age 20-70 years, Eastern
      Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate organ
      functions. Eligible patients with previously untreated limited-stage SCLC
      received one cycle of etoposide plus cisplatin (intravenous etoposide 100 mg/m(2)
      on days 1-3; intravenous cisplatin 80 mg/m(2) on day 1) plus AHTRT (1.5 Gy twice
      daily, 5 days a week, total 45 Gy over 3 weeks). Patients without progressive
      disease following induction therapy were randomised (1:1 ratio, using a
      minimisation method with biased-coin assignment balancing on ECOG performance
      status [0 vs 1], response to induction chemoradiotherapy [complete response plus
      near complete response vs partial response and stable disease], and institution)
      to receive either three further cycles of consolidation etoposide plus cisplatin
      or irinotecan plus cisplatin (intravenous irinotecan 60 mg/m(2) on days 1, 8, 15;
      intravenous cisplatin 60 mg/m(2) on day 1). Patients, physicians, and
      investigators were aware of allocation. The primary endpoint was overall survival
      after randomisation; primary analysis was by intention to treat. This trial is
      registered with ClinicalTrials.gov, number NCT00144989, and the UMIN Clinical
      Trials Registry, number C000000095. FINDINGS: 281 patients were enrolled between
      Sept 1, 2002, and Oct 2, 2006. After induction etoposide plus cisplatin and
      AHTRT, 258 patients were randomised to consolidation etoposide plus cisplatin
      (n=129) or irinotecan plus cisplatin (n=129). In the etoposide plus cisplatin
      group, median overall survival was 3.2 years (95% CI 2.4-4.1). In the irinotecan
      and cisplatin group, median overall survival was 2.8 years (95% CI 2.4-3.6);
      overall survival did not differ between the two groups (hazard ratio 1.09 [95% CI
      0.80-1.46], one-sided stratified log-rank p=0.70). The most common adverse events
      of grade 3 or 4 were neutropenia (120 [95%] in the etoposide plus cisplatin group
      vs 101 [78%] in the irinotecan plus cisplatin group), anaemia (44 [35%] vs 50
      [39%]), thrombocytopenia (26 [21%] vs six [5%]), febrile neutropenia (21 [17%] vs
      18 [14%]), and diarrhoea (two [2%] vs 13 [10%]). There was one treatment-related
      adverse event leading to death in each group (radiation pneumonitis in the
      etoposide plus cisplatin group; brain infarction in the irinotecan plus cisplatin
      group). INTERPRETATION: Four cycles of etoposide plus cisplatin and AHTRT should
      continue to be the standard of care for limited-stage SCLC. FUNDING: National
      Cancer Center and the Ministry of Health, Labour, and Welfare of Japan.

PMID- 24309371
TI  - Overexpressed TGF-beta in subchondral bone leads to mandibular condyle
      degradation.
AB  - Emerging evidence has implied that subchondral bone plays an important role
      during osteoarthritis (OA) pathology. This study was undertaken to investigate
      whether abnormalities of the condylar subchondral bone lead to temporomandibular
      joint (TMJ) OA. We used an osteoblast-specific mutant TGF-beta1 transgenic mouse,
      the CED mouse, in which high levels of active TGF-beta1 occur in bone marrow,
      leading to abnormal bone remodeling. Subchondral bone changes in the mandibular
      condyles were investigated by micro-CT, and alterations in TMJ condyles were
      confirmed by histopathological and immunohistochemical analysis. Abnormalities in
      the condylar subchondral bone, characterized as fluctuant bone mineral density
      and microstructure and increased but uncoupled activity of osteoclasts and
      osteoblasts, were apparent in the 1- and 4-month CED mouse groups, while obvious
      cartilage degradation, in the form of cell-free regions and proteoglycan loss,
      was observed in the 4-month CED group. In addition, increased numbers of
      apoptotic chondrocytes and MMP9- and VEGF-positive chondrocytes were observed in
      the condylar cartilage in the 4-month CED group, but not in the 1-month CED
      group, compared with their respective age-matched controls. This study
      demonstrated that progressive degradation of mandibular condylar cartilage could
      be induced by the abnormal remodeling of the underlying subchondral bone during
      TMJOA progression.

PMID- 24309372
TI  - Historic of therapeutic efficacy of albendazol sulphoxide administered in
      different routes, dosages and treatment schemes, against Taenia saginata
      cysticercus in cattle experimentally infected.
AB  - The present study aimed to notify the history of albendazole sulphoxide (ALB-SO)
      and albendazole (ALBZ) efficacy against Taenia saginata cysticercus (Cysticercus
      bovis) parasitizing experimentally infected bovines. A total of 11 efficacy
      trials were performed between the years of 2002 and 2010. In order to perform
      these trials, animals were individually inoculated with 2*10(4) eggs of T.
      saginata in each study's day zero (D0). For every trial, a positive control group
      (untreated infected animals) and a negative control group (animals that were
      neither infected nor treated) were used. ALB-SO or ALB were administered in the
      different dosages, in different days of treatments. In a last study with this
      formulation, this active principle was administered orally, mixed with the
      mineral supplement, on the 60th DPI, in a dosage of 30mg/kg. In all trials, on
      the 100th DPI, all animals were euthanized and submitted to the sequenced slicing
      of 26 anatomical segments (fragments of approximately five millimeters) for the
      survey of T. saginata cysticercus. With the obtained results it is possible to
      verify that in the first trials, conducted in 2002, ALB-SO reached, independently
      of dosage and treatment scheme, efficacies superior to 98% (arithmetic means).
      The trials conducted in 2005 (2.5mg/kg on the 30th, 60th, and 90th DPI) obtained
      values of efficacy all inferior to 60%. In 2008, the trials with 2.5 and 7.7mg/kg
      demonstrated efficacy values inferior to 40%, for both dosages and treatment
      schemes (30th/60th/90th DPI and 60th DPI). When this formulation was administered
      orally on the dosage of 30mg/kg on the 60th DPI, the efficacy against T. saginata
      cysticercus reached 88.28%. ALB administered orally showed efficacy values of
      0.0%, 29.88% and 28.64% in the dosages of 5, 10 and 15mg/kg, respectively, using
      the treatment schemes described above for each dosage. Based on the results of
      these trials, conducted in an eight year period (2002-2010) using the sequenced
      slicing method for evaluating the efficacy of the aforementioned formulations
      against T. saginata cysticercus, it is possible to observe that, amongst the few
      molecules used in the chemotherapic treatment against T. saginata larvae, ALB-SO,
      administered in varied routes, dosages and treatment schemes, the studies
      conducted in 2008, 2009, and 2010, have a low therapeutic efficacy against C.
      bovis in Brazil, while ALBZ had insignificant efficacy values against T. saginata
      larvae parasitizing experimentally infected bovines. However, future studies
      using molecular biology will be necessary to assess whether the difference on the
      efficacy of the ALB-SO can be related to strain or another specific factor. 

PMID- 24309373
TI  - Increased expression of mdig predicts poorer survival of the breast cancer
      patients.
AB  - Breast cancer is the most common cancer and the second leading cause of cancer
      death among women of all races and Hispanic origin populations in the United
      States. In the present study, we reported that the survival time of the breast
      cancer patients is influenced by the expression level of mdig, a previously
      identified lung cancer-associated oncogene encoding a JmjC-domain protein. By
      checking the expression levels of mRNA and protein of mdig through both RT-PCR
      and immunohistochemistry in samples from 204 patients, we noticed that about 30%
      of breast cancer samples showed increased expression of mdig. Correlation of the
      mdig expression levels with the survival time of the breast cancer patients
      indicated a clear inverse relationship between mdig expression and patient
      survival, including poorer overall survival, distant metastasis free survival,
      relapse free survival, and post-progression survival. Taken together, these data
      suggest that an increased expression of mdig is an important prognostic factor
      for poorer survival time of the breast cancer patients. 

PMID- 24309374
TI  - Molecular characterization and differential expression of multiple goose dopamine
      D2 receptors.
AB  - Dopamine D2 receptor (DRD2) gene, a member of the dopamine receptors gene family,
      has been studied as a candidate gene for broodiness due to its special effects on
      avian prolactin secretion. Here, the genomic DNA and cDNA sequences of goose
      (Anser cygnoides) DRD2 gene were cloned and characterized for the first time. The
      goose DRD2 cDNA is 1353bp in length and encodes a protein of 450 amino acids. The
      length of goose DRD2 genomic DNA is 8350bp, including seven exons and six
      introns. We identified four goose DRD2 variants, which were generated due to
      alternative splicing. Bioinformatics analysis indicates that all the deduced DRD2
      amino acid sequences contain seven putative transmembrane domains and four
      potential N-glycosylation sites. A phylogenetic tree based on amino acid
      sequences displays that the goose DRD2 protein is closely related to those of
      avian species. Semi-quantitative RT-PCR analysis demonstrates that the DRD2-1,
      DRD2-2 and DRD2-4 transcripts are differentially expressed in the pituitary,
      ovary, hypothalamus, as well as in the kidney, whereas the DRD2-3 transcript is
      widely expressed in all the examined tissues at different levels. Meanwhile, 54
      single nucleotide polymorphisms (SNPs) and 4 insert-deletion (indel) variations
      were identified in the coding region and partial intron region of the goose DRD2
      gene. Those findings will help us gain insight into the functions of the DRD2
      gene in geese. 

PMID- 24309375
TI  - Zipping, entanglement, and the elastic modulus of aligned single-walled carbon
      nanotube films.
AB  - Reliably routing heat to and from conversion materials is a daunting challenge
      for a variety of innovative energy technologies--from thermal solar to automotive
      waste heat recovery systems--whose efficiencies degrade due to massive
      thermomechanical stresses at interfaces. This problem may soon be addressed by
      adhesives based on vertically aligned carbon nanotubes, which promise the
      revolutionary combination of high through-plane thermal conductivity and
      vanishing in-plane mechanical stiffness. Here, we report the data for the in
      plane modulus of aligned single-walled carbon nanotube films using a
      microfabricated resonator method. Molecular simulations and electron microscopy
      identify the nanoscale mechanisms responsible for this property. The zipping and
      unzipping of adjacent nanotubes and the degree of alignment and entanglement are
      shown to govern the spatially varying local modulus, thereby providing the route
      to engineered materials with outstanding combinations of mechanical and thermal
      properties. 

PMID- 24309376
TI  - Pepducin targeting the C-X-C chemokine receptor type 4 acts as a biased agonist
      favoring activation of the inhibitory G protein.
AB  - Short lipidated peptide sequences derived from various intracellular loop regions
      of G protein-coupled receptors (GPCRs) are named pepducins and act as allosteric
      modulators of a number of GPCRs. Recently, a pepducin selectively targeting the C
      X-C chemokine receptor type 4 (CXCR4) was found to be an allosteric agonist,
      active in both cell-based assays and in vivo. However, the precise mechanism of
      action of this class of ligands remains poorly understood. In particular, given
      the diversity of signaling effectors that can be engaged by a given receptor, it
      is not clear whether pepducins can show biased signaling leading to functional
      selectivity. To explore the ligand-biased potential of pepducins, we assessed the
      effect of the CXCR4 selective pepducin, ATI-2341, on the ability of the receptor
      to engage the inhibitory G proteins (Gi1, Gi2 and Gi3), G13, and beta-arrestins.
      Using bioluminescence resonance energy transfer-based biosensors, we found that,
      in contrast to the natural CXCR4 ligand, stromal cell-derived factor-1alpha,
      which promotes the engagement of the three Gi subtypes, G13 and the two beta
      arrestins, ATI-2341 leads to the engagement of the Gi subtypes but not G13 or the
      beta-arrestins. Calculation of the transduction ratio for each pathway revealed a
      strong negative bias of ATI-2341 toward G13 and beta-arrestins, revealing
      functional selectivity for the Gi pathways. The negative bias toward beta
      arrestins results from the reduced ability of the pepducin to promote GPCR kinase
      mediated phosphorylation of the receptor. In addition to revealing ligand-biased
      signaling of pepducins, these findings shed some light on the mechanism of action
      of a unique class of allosteric regulators. 

PMID- 24309378
TI  - Microbial terroir for wine grapes.

PMID- 24309377
TI  - Osmosensory signaling in Mycobacterium tuberculosis mediated by a eukaryotic-like
      Ser/Thr protein kinase.
AB  - Bacteria are able to adapt to dramatically different microenvironments, but in
      many organisms, the signaling pathways, transcriptional programs, and downstream
      physiological changes involved in adaptation are not well-understood. Here, we
      discovered that osmotic stress stimulates a signaling network in Mycobacterium
      tuberculosis regulated by the eukaryotic-like receptor Ser/Thr protein kinase
      PknD. Expression of the PknD substrate Rv0516c was highly induced by osmotic
      stress. Furthermore, Rv0516c disruption modified peptidoglycan thickness,
      enhanced antibiotic resistance, and activated genes in the regulon of the
      alternative sigma-factor SigF. Phosphorylation of Rv0516c regulated the abundance
      of EspA, a virulence-associated substrate of the type VII ESX-1 secretion system.
      These findings identify an osmosensory pathway orchestrated by PknD, Rv0516c, and
      SigF that enables adaptation to osmotic stress through cell wall remodeling and
      virulence factor production. Given the widespread occurrence of eukaryotic-like
      Ser/Thr protein kinases in bacteria, these proteins may play a broad role in
      bacterial osmosensing. 

PMID- 24309379
TI  - Shear shocks in fragile networks.
AB  - A minimal model for studying the mechanical properties of amorphous solids is a
      disordered network of point masses connected by unbreakable springs. At a
      critical value of its mean connectivity, such a network becomes fragile: it
      undergoes a rigidity transition signaled by a vanishing shear modulus and
      transverse sound speed. We investigate analytically and numerically the linear
      and nonlinear visco-elastic response of these fragile solids by probing how shear
      fronts propagate through them. Our approach, which we tentatively label shear
      front rheology, provides an alternative route to standard oscillatory rheology.
      In the linear regime, we observe at late times a diffusive broadening of the
      fronts controlled by an effective shear viscosity that diverges at the critical
      point. No matter how small the microscopic coefficient of dissipation, strongly
      disordered networks behave as if they were overdamped because energy is
      irreversibly leaked into diverging nonaffine fluctuations. Close to the
      transition, the regime of linear response becomes vanishingly small: the tiniest
      shear strains generate strongly nonlinear shear shock waves qualitatively
      different from their compressional counterparts in granular media. The inherent
      nonlinearities trigger an energy cascade from low to high frequency components
      that keep the network away from attaining the quasi-static limit. This mechanism,
      reminiscent of acoustic turbulence, causes a superdiffusive broadening of the
      shock width. 

PMID- 24309380
TI  - Male infanticide and primate monogamy.

PMID- 24309381
TI  - An intervention to decrease stigma in young adults with sickle cell disease.
AB  - Young adults with sickle cell disease (SCD) are often stigmatized when they seek
      care for pain. The purpose of this pilot study was to test an intervention to
      decrease health-related stigma during care-seeking. Young adults with SCD ages 18
      to 35 years (n = 90) were randomized to either the care-seeking intervention
      (CSI) or an attention control group that participated in life review interviews.
      The two groups were compared by t tests and longitudinal data analyses on the
      change from baseline to the last time point in total health-related stigma and
      health-related stigma by doctors. Findings suggest that the CSI was associated
      with significant increased awareness of perceived total stigma and stigma by
      doctors compared with the attention control group. These findings are promising
      in terms of lessons learned from a pilot intervention that focused on the role
      communication skills play in decreasing health-related stigma in young adults
      with SCD. 

PMID- 24309382
TI  - Whither goest thou, radiopharmaceutical therapy?

PMID- 24309383
TI  - Performance of whole-body integrated 18F-FDG PET/MR in comparison to PET/CT for
      evaluation of malignant bone lesions.
AB  - Because of its higher soft-tissue contrast, whole-body integrated PET/MR offers
      potential advantages over PET/CT for evaluation of bone lesions. However, unlike
      PET/CT, PET/MR ignores the contribution of cortical bone in the attenuation map.
      Thus, the aims of this study were to evaluate the diagnostic performance of whole
      body integrated (18)F-FDG PET/MR specifically for bone lesions and to analyze
      differences in standardized uptake value (SUV) quantification between PET/MR and
      PET/CT. METHODS: One hundred nineteen patients with (18)F-FDG-avid primary
      malignancies underwent a single-injection, dual-imaging protocol using (18)F-FDG
      on a PET/CT scanner and a subsequent PET/MR scan with a T1-weighted volumetric
      interpolated breath-hold examination (VIBE) Dixon sequence for attenuation
      correction and an unenhanced coronal T1-weighted turbo spin-echo (TSE) sequence
      for bone analysis. Three sets of images (CT with PET [from PET/CT; set A], T1
      weighted VIBE Dixon with PET [set B], and T1-weighted TSE with PET [both from
      PET/MR; set C]) were analyzed. Two readers rated every lesion using a 4-point
      scale for lesion conspicuity on PET, a 4-point scale for anatomic allocation of
      PET-positive lesions, and a 5-point scale for the nature of every lesion based on
      its appearance on morphologic imaging and uptake on PET. For all lesions and for
      representative regions of normal bone, SUV analysis was performed for PET/MR and
      PET/CT. RESULTS: In total, 98 bone lesions were identified in 33 of 119 patients,
      and 630 regions of normal bone were analyzed. Visual lesion conspicuity on PET
      was comparable for PET/CT (mean rating, 2.82 +/- 0.45) and PET/MR (2.75 +/- 0.51;
      P = 0.3095). Anatomic delineation and allocation of suggestive lesions was
      significantly superior with T1-weighted TSE MRI (mean rating, 2.84 +/- 0.42)
      compared with CT (2.57 +/- 0.54, P = 0.0001) or T1-weighted VIBE Dixon MRI (2.57
      +/- 0.54, P = 0.0002). No significant difference in correct classification of
      malignant bone lesions was found among sets A (85/90), B (84/90), and C (86/90).
      For bone lesions and regions of normal bone, a highly significant correlation
      existed between the mean SUVs for PET/MR and PET/CT (R = 0.950 and 0.917,
      respectively, each P < 0.001). However, substantially lower mean SUVs were found
      for PET/MR than for PET/CT both for bone lesions (12.4% +/- 15.5%) and for
      regions of normal bone (30.1% +/- 27.5%). CONCLUSION: Compared with PET/CT, fully
      integrated whole-body (18)F-FDG PET/MR is technically and clinically robust for
      evaluation of bone lesions despite differences in attenuation correction. PET/MR,
      including diagnostic T1-weighted TSE sequences, was superior to PET/CT for
      anatomic delineation and allocation of bone lesions. This finding might be of
      clinical relevance in selected cases--for example, primary bone tumors, early
      bone marrow infiltration, and tumors with low uptake on PET. Thus, a diagnostic
      T1-weighted TSE sequence is recommended as a routine protocol for oncologic
      PET/MR.

PMID- 24309384
TI  - Effect of pheniramine maleate on reperfusion injury in brain tissue.
AB  - BACKGROUND: The aim of this study was to investigate the protective effects of
      methylprednisolone (Pn), which is a potent anti-inflammatory agent, and
      pheniramine maleate (Ph), which is an antihistaminic with some anti-inflammatory
      effects, on reperfusion injury in brain developing after ischemia of the left
      lower extremity of rats. MATERIAL AND METHODS: Twenty-eight randomly selected
      male Sprague-Dawley rats were divided into 4 groups: Group 1 was the control
      group, Group 2 was the sham group (I/R), Rats in Group 3 were subjected to I/R
      and given Ph, and rats in Group 4 were subjected to I/R and given Pn. A
      tourniquet was applied at the level of left groin region of subjects in the I/R
      group after induction of anesthesia. One h of ischemia was performed with no drug
      administration. In the Ph group, half of a total dose of 10 mg/kg Ph was
      administered intraperitoneally before ischemia and the remaining half before
      reperfusion. In the Pn group, subjects received a single dose of 50 mg/kg Pn
      intraperitoneally at the 30th min of ischemia. Brains of all subjects were
      removed after 24 h for examination. RESULTS: Malondialdehyde (MDA) levels of the
      prefrontal cortex were significantly lower in the Ph group than in the I/R group
      (p<0.05). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme
      activities were found to be significantly higher in the Ph group than in the I/R
      group (p<0.05). Histological examination demonstrated that Ph had protective
      effects against I/R injury developing in the brain tissue. CONCLUSIONS: Ph has a
      protective effect against ischemia/reperfusion injury created experimentally in
      rat brains.

PMID- 24309385
TI  - Injectable 3-D fabrication of medical electronics at the target biological
      tissues.
AB  - Conventional transplantable biomedical devices generally request sophisticated
      surgery which however often causes big trauma and serious pain to the patients.
      Here, we show an alternative way of directly making three-dimensional (3-D)
      medical electronics inside the biological body through sequential injections of
      biocompatible packaging material and liquid metal ink. As the most typical
      electronics, a variety of medical electrodes with different embedded structures
      were demonstrated to be easily formed at the target tissues. Conceptual in vitro
      experiments provide strong evidences for the excellent performances of the
      injectable electrodes. Further in vivo animal experiments disclosed that the
      formed electrode could serve as both highly efficient ECG (Electrocardiograph)
      electrode and stimulator electrode. These findings clarified the unique features
      and practicability of the liquid metal based injectable 3-D fabrication of
      medical electronics. The present strategy opens the way for directly
      manufacturing electrophysiological sensors or therapeutic devices in situ via a
      truly minimally invasive approach. 

PMID- 24309386
TI  - Strain induced superconductivity in the parent compound BaFe2As2.
AB  - The discovery of superconductivity with a transition temperature, Tc, up to 65 K
      in single-layer FeSe (bulk Tc=8 K) films grown on SrTiO3 substrates has attracted
      special attention to Fe-based thin films. The high Tc is a consequence of the
      combined effect of electron transfer from the oxygen-vacant substrate to the FeSe
      thin film and lattice tensile strain. Here we demonstrate the realization of
      superconductivity in the parent compound BaFe2As2 (no bulk Tc) just by tensile
      lattice strain without charge doping. We investigate the interplay between strain
      and superconductivity in epitaxial BaFe2As2 thin films on Fe-buffered MgAl2O4
      single crystalline substrates. The strong interfacial bonding between Fe and the
      FeAs sublattice increases the Fe-Fe distance due to the lattice misfit, which
      leads to a suppression of the antiferromagnetic spin density wave and induces
      superconductivity with bulk Tc~10 K. These results highlight the role of
      structural changes in controlling the phase diagram of Fe-based superconductors. 

PMID- 24309388
TI  - WITHDRAWN: Respiratory syncytial virus infection is strongly correlated with
      decreased mean platelet volume.
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- 24309387
TI  - Comorbidities and polypharmacy impact on complete cytogenetic response in chronic
      myeloid leukaemia elderly patients.
AB  - BACKGROUND: In older patients comorbidity and polypharmacy can significantly
      influence the success of the treatment, as well as the cognitive and psycho
      social aspects. A significant proportion of chronic myeloid leukaemia (CML)
      patients are "elderly": in the past the aim of therapy in this subset of patients
      was only to contain the leukaemic mass, but nowadays, with the advent of the
      protein-tyrosine kinase inhibitors, also elderly patients can access these
      treatments. We want to assess if even old CML patients, with a correct geriatric
      evaluation, can be successfully treated with protein-tyrosine kinase inhibitors.
      METHODS: A complete geriatric evaluation in 16 old CML patients aged >65years
      treated with TKI was performed in order to assess the comorbidity, the
      polypharmacy and the cognitive, physical and psychological states. The Charlson
      comorbity index (CCI) and the polypharmacy were correlated to the obtained
      cytogenetic response. Seven scales of geriatric evaluation were used to assess
      the autonomy of patients before they were included into the study. RESULTS: In
      our cohort of elderly patients treated with imatinib, comorbidities and
      polypharmaco-therapy demonstrated an influence on TKI therapeutic success. In
      fact, the majority of complete cytogenetic response was obtained by patients who
      presented a low score of CCI and did not take any other drugs other than TKI.
      CONCLUSION: Also old chronic myeloid leukaemia patients can benefit from TKI
      treatment if a good cooperation between the haematologist and the geriatrician is
      established.

PMID- 24309390
TI  - GAPS in implementing health assessments in primary care: a literature review.
AB  - Patient-reported health data are critical components of patient-centered health
      care. However, barriers related to acquisition, implementation, and data use have
      not been well characterized. We conducted a systematic review of literature about
      health assessments in ambulatory and primary care covering 2 domains: (1) best
      practices in health assessments in primary care and (2) integration of health
      assessments into electronic health records. Our review found that training and
      standardization of practice workflows improves implementation of health
      assessments; however, gaps remain on identification and selection of health
      assessments, integration with electronic health records, and optimal intervals of
      health assessments administration.

PMID- 24309391
TI  - Comparison of emergency nurses association Emergency Severity Triage and
      Australian emergency mental health triage systems for the evaluation of
      psychiatric patients.
AB  - The use of a triage system in the emergency department allows for the ability to
      reliably assign patients for treatment within a short amount of time in order to
      prioritize and treat on the basis of patients injury and illness. A 5 point
      triage system has been shown to have the highest correlation with effective
      resource utilizations, lower time to be seen and treatment times, and admission
      or release outcomes for patients. The problem is, however, that these triage
      scales were developed on the basis of physical illness and not on the ever
      increasing number of patients who present with mental illness. This article
      compares one physical and one specific mental illness-based triage system to
      measure the differences in times to be seen by a physician. It found that the
      specialized psychiatric triage system decreased wait times and allowed symptoms
      to be addressed sooner for patients presenting with psychiatric complaints.

PMID- 24309392
TI  - HIE-i-health information exchange with intelligence.
AB  - This article demonstrates the development and pilot testing of an innovative
      approach to implement health information exchange with intelligence (HIE-i) in
      primary care settings. Records of 346 patients were studied in 6 primary care
      practices. Clinical workflows were evaluated by time motion studies and
      observations. A viable and sustained HIE connection was adopted by primary care
      clinicians. Documentation and delivery of several preventive services, medication
      reconciliation, and workflow efficiency improved. The study was able to establish
      a sustained and effective HIE implementation. More research is needed to
      determine the clinical impact and sustainability of the HIE-i approach. 

PMID- 24309393
TI  - The use of shared medical appointments in the care of the elderly.
AB  - The shared medical appointment is a model of delivering outpatient care in which
      several patients interact simultaneously with 1 or several providers. These
      appointments were developed as an efficient means of delivering education about
      chronic medical conditions to elderly individuals. In several, but not all
      trials, chronically ill elderly and younger patients have achieved better general
      and disease-specific outcomes. However, because the studies have compared these
      appointments with conventional care, it is not clear whether advantages occur
      because of the unique characteristics of such an outpatient visit or because of
      more time spent or greater numbers of providers interacting with patients.

PMID- 24309394
TI  - Chronic care model as a framework to improve diabetes care at an academic
      internal medicine faculty-resident practice.
AB  - We implemented a quality improvement project for diabetes care in a faculty
      resident internal medicine practice, using the Chronic Care Model framework. We
      created a planned visit clinic, used a stepwise medication algorithm, and self
      management support. The intervention was effective for patients with
      glycohemoglobin A1c levels 10 or above (P = .0075) when compared with usual care
      after adjusting for all significant predictors. Compliance with foot examinations
      increased by 72% (P < .0001) and pneumococcal vaccinations by 25% (P = .0115). We
      believe that the Chronic Care Model can be successfully integrated into faculty
      resident practices and provides a model for further exploration into disease
      management education in academic settings.

PMID- 24309395
TI  - The DNA of cancer centers: an introduction to planning and design.

PMID- 24309396
TI  - Avoidable hospitalizations for ambulatory care sensitive conditions as an
      indicator of primary health care effectiveness in Argentina.
AB  - Avoidable hospitalizations for ambulatory care sensitive conditions (AH-ACSCs)
      identify health problems that could be avoided by improving primary health care
      (PHC). On the basis of hospital discharges from Argentine public sector
      facilities, an expert panel convened to define a list of AH-ACSCs for children
      and adults. AH-ACSCs represented less than 30% of hospitalizations. Compared with
      country averages, poorer districts showed large differences in trends for adults
      but not for children. Despite that AH-ACSCs have demonstrated empirical validity
      to evaluate health system performance, its implementation to assess PHC in
      countries like Argentina, with pluralistic and fragmented health care systems,
      remains a big challenge.

PMID- 24309397
TI  - Community health worker integration into the health care team accomplishes the
      triple aim in a patient-centered medical home: a Bronx tale.
AB  - Community health workers are ideally suited to the care coordination niche within
      the patient-centered medical home (PCMH) team, but there are few case studies
      detailing how to accomplish this integration. This qualitative study documents
      how community health workers (CHWs) were integrated into a PCMH in South Bronx,
      New York. Results show that integration was linked to clear definition of their
      care coordination role within the care team, meticulous recruitment, training and
      supervision by a senior CHW, shared leadership of the care management team, and
      documented value for money. By helping the team understand patients' backgrounds,
      constraints, and preferences, they helped everyone genuinely focus on the
      patient.

PMID- 24309399
TI  - CT classification and endovascular management of isolated dissection of the
      superior mesenteric artery with anatomical variations.

PMID- 24309400
TI  - The "open" chimney graft technique for juxtarenal aortic aneurysms with
      discrepant renal arteries.
AB  - OBJECTIVES: A straightforward original Chimney Graft (CG) protocol has been
      developed at our institution in selected cases of juxtarenal aortic aneurysm
      (JRAA). The aim of this study was to present our clinical experience of
      consecutive series with use of uncovered self-expanding stent (SES) as "Open
      Chimney" (OCh) in the endovascular repair (EVAR) of JRAA. METHODS: A standard
      endograft with suprarenal fixation struts is delivered with its proximal covered
      edge just below the highest RA in JRAA presenting the ostium of the two renal
      arteries at a different aortic level and the distance between the highest renal
      artery and the beginning of the aneurysm (improved landing zone) >=10 mm. The low
      lying renal artery is maintained patent by the OCh graft (standard SES) delivered
      from left brachial access (6 Fr). All clinical, anatomical, and operative data
      were prospectively collected and retrieved for the study analysis. RESULTS: From
      July 2010 to November 2012, OCh EVAR was offered to 22 consecutive patients
      considered unfit for JRAA open repair. All procedures were technically successful
      with aneurysm exclusion and patent OCh graft. One small perioperative type Ia
      endoleak spontaneously disappeared at the 3-month CT control. One patient died
      because of acute decompensated heart failure. One patient presented a left
      hemispheric stroke. The median follow-up of 18 months (range 7-35) showed
      aneurysm exclusion in all patients without type I and III endoleaks, SES
      stenosis, and/or renal impairment. CONCLUSIONS: OCh-EVAR is a straightforward
      technique that can be employed in selected cases of JRAA, avoiding the more
      complex and expensive fenestrated EVAR.

PMID- 24309401
TI  - The effect of different beta-blockers on vascular graft nitric oxide levels:
      comparison of nebivolol versus metoprolol.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of the
      vasodilating beta-blocker nebivolol and the cardioselective beta-blocker
      metoprolol on nitric oxide (NO) levels at vascular graft endothelium and vasa
      vasorum compared to controls in patients undergoing coronary artery bypass graft
      surgery. METHODS: This was a prospective study. Fifty-five patients were divided
      into three groups: nebivolol group (group N, n = 23), metoprolol group (group M,
      n = 16), and control group (group A, n = 16). Group N received nebivolol 5 mg
      once daily, and group M received metoprolol 50 mg once daily for 15 days in the
      preoperative period. Control patients did not use beta-blocker therapy. Tissue
      samples of both left internal mammary artery (LIMA) and saphenous vein grafts
      were investigated for NO activity using immunohistochemical methods. RESULTS:
      Demographic characteristics and risk factors were similar between groups. We
      observed the highest NO activity in group N in both endothelial and vasa vasorum
      samples of LIMA and saphenous veins. NO activity of metoprolol group was similar
      to controls. CONCLUSIONS: According to our results, we think that nebivolol may
      be safer and preferable in order to diminish graft spasm in patients undergoing
      coronary artery bypass graft surgery due to the NO-mediated vasodilating effect.

PMID- 24309402
TI  - Detection of genes encoding for virulence and adherence factors in Escherichia
      coli isolated in slaughtered Sarda breed sheep.
AB  - In order to investigate the pathogenic profile of Escherichia coli hosted in
      "Sarda" sheep, autochthonous race present in Sardinia, thirty-seven E. coli
      strains collected from different sources (fleeces, carcass swabs and gut mucosa)
      of pre-chill slaughtered sheep (ewes and lambs) were serotyped using pheno- and
      genotypic methods. Furthermore, the presence of genes encoding for virulence
      factors and mediating for localized mucosal adherence factors was investigated,
      and pulsed-field gel electrophoresis (PFGE) characterization was performed.
      Twenty-one (56.8%) of the isolates belonged to O91 serogroup and sixteen (43.2%)
      belonged to nine different serotypes (O5:H11, O8:H14, O26:H2, O38:H26, O116:H9,
      O116:H11, O132:H34, O149:H?, O161:H-). Of these non-O91 strains, five (13.5%)
      were able to produce verocytotoxin (VT) and were ascribed to VTEC pathogroup,
      eleven (29.7%) were attributed to the Enteropathogenic E. coli (EPEC) pathogroup;
      the other strains (n.21) cannot be ascribed to a pathogenic group. However,
      various associated virulence genes were observed in all isolated strains.
      Macrorestriction analysis highlighted a large heterogeneity of the E. coli
      strains. The results confirm the role of sheep as reservoir of pathogenic E. coli
      serotypes potentially able to colonize and to damage the intestinal mucosa.

PMID- 24309403
TI  - Pathogenesis of GIII.2 bovine norovirus, CV186-OH/00/US strain in gnotobiotic
      calves.
AB  - The pathogenesis of GIII.2 bovine norovirus (BoNoV) is not well understood. Our
      study demonstrated persisting diarrhea and prolonged fecal shedding, but with a
      lack of significant intestinal lesions in gnotobiotic (Gn) calves infected with
      GIII.2 BoNoV, CV186-OH/00/US strain. Nine 4 to 7-day-old Angus/Jersey crossbred
      Gn calves were orally inoculated with 10.0-11.9 log10 genomic equivalents
      (GE)/calf of CV186-OH (n=7) or mock (n=2). Calves were euthanized at post
      inoculation day (PID) 1 (n=1) when moderate to severe lethargy was observed and
      at PIDs 2-6 (n=4) after lethargy had subsided. Two calves were kept longer term
      (until PID 30) for monitoring fecal shedding patterns by TaqMan real-time RT-PCR
      (qRT-PCR). Most infected calves exhibited two clinical signs: (i) acute but
      persisting diarrhea and (ii) acute moderate to severe lethargy. The two infected
      calves, followed longer-term, had prolonged fecal viral RNA shedding [peak
      average titer of 11.8 (+/- 0.2) log10GE/ml] at least until PID 20. By qRT-PCR, 5
      infected calves had low viral RNA titers in serum, ranging from 4.0 to 5.8
      log10GE/ml, at PIDs 1-5, but not (<2.7 log10GE/ml) at PIDs 6-30. The latter
      observation coincided with the presence of serum IgG antibody to BoNoV at PIDs 8
      30. Collectively, the GIII.2 BoNoV strain CV186-OH induced only mild
      enteropathogenicity, evident by the lack of significant intestinal lesions, but
      it led to persisting mild diarrhea and prolonged fecal virus shedding in Gn
      calves. The prolonged fecal shedding of GIII.2 BoNoV might partially explain how
      this virus is maintained as endemic infections in cattle.

PMID- 24309404
TI  - Characterization of the North American beaver (Castor canadensis) papillomavirus
      genome.
AB  - The papillomaviruses comprise a large group of viruses that cause proliferations
      of the stratified squamous epithelium of skin and mucosa in a variety of animals.
      An earlier report identified a novel papillomavirus of the North American beaver,
      Castor canadensis (CcanPV1) that was associated with cutaneous exophytic lesions.
      In the current study, we determined the sequence of the complete 7435 basepair
      genome of CcanPV1. The genome contains an Upstream Regulatory Region located
      between the end of L1 and the start of E6, and seven canonical papillomavirus
      open reading frames encoding five early (E6, E7, E1, E2, and E4) and two late (L2
      and L1) proteins. No E5 open reading frame was detected. Phylogenetic analysis of
      the CcanPV1 genome places the virus between the genera Kappapapillomavirus and
      Mupapillomavirus. Analyses of the papillomavirus genomes detected in different
      species of the order Rodentia indicate these viruses do not form a monophyletic
      clade. 

PMID- 24309405
TI  - Combinatorial HLA-peptide bead libraries for high throughput identification of
      CD8+ T cell specificity.
AB  - Comprehensive antigenic characterization of a T cell population of unknown
      specificity is challenging. Existing MHC class I expression systems are limited
      by the practical difficulty of probing cell populations with an MHC class I
      peptide library and the cross-reactivity of T cells that are able to recognise
      many variants of an index peptide. Using emulsion PCR and emulsion in vitro
      transcription/translation of a random library of peptides conjugated to CD8-null
      HLA-A*0201 on beads, we probed HLA-A*0201-restricted T cells with specificity for
      influenza, CMV and EBV. We observed significant enrichment for sequences
      containing HLA-A2 anchors and correct viral fragments for all T cell populations.
      HLA bead display provides a novel approach to identify the specificity of T
      cells. 

PMID- 24309407
TI  - Prevalence, clinical characteristics and outcome of pulmonary hypertension among
      admitted heart failure patients.
AB  - BACKGROUND: There is paucity of data in Africa on the prevalence of pulmonary
      hypertension (PHT) and its impact on morbidity and short-term mortality in heart
      failure (HF) patients. The aim of this study was to assess the prevalence of PHT,
      its clinical characteristics and in-hospital mortality among HF patients admitted
      to a referral hospital in Nigeria. METHODS: The study was carried out on serially
      admitted HF patients who satisfied the inclusion criteria, in a Nigerian tertiary
      health center. PHT was defined as the presence of mean pulmonary artery pressure
      (mPAP) of >=25 mmHg, assessed using Doppler echocardiography and Chemla formula.
      RESULTS: A total of 80 admitted HF patients were studied serially. 53 of them
      (66.25%) had PHT while the remaining 27 (33.75%) had normal mPAP. mPAP was 38.31
      +/- 12.23 mmHg and 16.39 +/- 5.48 mmHg (P < 0.001) for subjects with and without
      PHT, respectively. The most common cause of HF was hypertensive heart disease
      (HHD) (28 patients; 35%). Subjects with PHT had relatively lower systolic blood
      pressure (SBP) (P = 0.044), and larger left atrium (P = 0.036) and left ventricle
      (LV) at both end-diastole and end-systole (P = 0.036 and P = 0.008,
      respectively), and a trend toward lower LV ejection fraction (LVEF) (P = 0.053).
      There was no relationship between mPAP and N-terminal pro-B type natriuretic
      peptide (P > 0.05). A total of 12 HF patients (15.0%) died, out of whom 8 (66.7%)
      had PHT. Cardiogenic shock (P = 0.044) and trans-mitral flow velocities ratio (P
      = 0.023) were the independent determinants of in-hospital mortality. CONCLUSION:
      PHT was common among the admitted HF patients, and was associated with worse
      morbidity indices, and a trend toward higher mortality. We recommend that HF
      patients be screened for PHT, and its presence should be taken into consideration
      in the management and prognostication of affected patients.

PMID- 24309406
TI  - Ectropion and entropion in sub-Saharan Africa: how do we differ?
AB  - AIMS: To study the etiopathophysiology of ectropion and entropion in a sub
      Saharan tertiary eye care center and examine how it differs from reports
      elsewhere. METHODS AND MATERIALS: This was a retrospective audit of all
      consecutive patients who presented with ectropion or entropion to the
      oculoplastics clinic of a tertiary eye care unit. We reviewed the medical records
      of all such patients and data extracted include age, gender, etiopathology, and
      diagnosis. The primary oculoplastic disease was used in classifying the patients.
      The study period covered January 2008-June 2012. RESULTS: A total of 53 patients
      were identified constituting 37.3% of all eyelid diseases. Thirty-three (62.3%)
      were males. Forty-eight (90.6%) had ectropion, 43(89.6%) of which were
      cicatricial ectropion. Five (9.4%) had entropion. The median age group affected
      was 30-39 years (26.4%). There were no cases of congenital ectropion or
      entropion. The leading etiological factor was trauma in 36 cases (67.9%), which
      was mostly due to road traffic accidents (50.9%). CONCLUSIONS: This study
      highlights a difference in etiopathophysiology of ectropion and entropion in a
      sub-Saharan region when compared to reported data from developed countries. In
      Nigeria, ectropion (which is often cicatricial) is usually secondary to trauma
      whereas senile involution is the common cause in many developed countries. This
      finding has implications in appropriate planning and skill acquisition for
      surgical correction in this group of patients.

PMID- 24309408
TI  - Breaking bad news in clinical setting - health professionals' experience and
      perceived competence in Southwestern Nigeria: a cross sectional study.
AB  - BACKGROUND: Communication skills are vital in clinical settings because the
      manner in which bad news is delivered could be a huge determinant of responses to
      such news; as well as compliance with beneficial treatment option. Information on
      training, institutional guidelines and protocols for breaking bad news (BBN) is
      scarce in Nigeria. We assessed the training, experience and perceived competence
      of BBN among medical personnel in southwestern Nigeria. MATERIALS AND METHODS:
      The study was a cross-sectional descriptive study conducted out among doctors and
      nurses in two healthcare institutions in southwestern Nigeria using an anonymous
      questionnaire (adapted from the survey by Horwitz et al.), which focused on the
      respondents training, awareness of protocols in BBN; and perceived competence
      (using a Five-Point Likert Scale) in five clinical scenarios. We equally asked
      the respondents about an instance of BBN they have recently witnessed. RESULTS: A
      total of 113 of 130 selected (response rate 86.9%) respondents were studied.
      Eight (7.1%) of the respondents knew of the guidelines on BBN in the hospital in
      which they work. Twenty-three (20.3%) respondents claimed knowledge of a
      protocol. The median perceived competence rating was 4 out of 5 in all the
      clinical scenarios. Twenty-five (22.1%) respondents have had a formal training in
      BBN and they generally had significant higher perceived competence rating (P =
      0.003-0.021). There is poor support from fellow workers during instances of BBN.
      CONCLUSION: It appears that the large proportion of the respondents in this study
      were unconsciously incompetent in BBN in view of the low level of training and
      little or no knowledge of well known protocols for BBN even though self-rated
      competence is high. Continuous medical education in communication skills among
      health personnel in Nigeria is advocated.

PMID- 24309409
TI  - Exstrophy anomalies: preliminary review of 18 cases in Maiduguri, North-Eastern
      Nigeria.
AB  - BACKGROUND: Exstrophy anomalies, although rare, pose a tremendous challenge to
      both surgeons and surrogates. Management is intricate and experience with large
      members is restricted to a few centres worldwide. This report is a review of 18
      cases of these anomalies managed in University of Maiduguri Teaching Hospital
      (UMTH) over 8 years, highlighting the intricacies of management, and contributes
      to the existing data bank on this subject matter in our environment. MATERIALS
      AND METHODS: We reviewed the records of all cases of anomalies that were managed
      in the index hospital from December 2002 to December 2010. RESULTS: Eighteen
      cases were studied. The youngest was a 2-day-old neonate and the oldest was 6
      years at repair, with a median age of 4 months. There were 7 boys and 9 girls
      with bladder exstrophy, and the remaining two were girls with cloacal exstrophy,
      giving a male-female ratio of 7:11 for the exstrophy anomalies. Eight patients
      (33.5%) had associated congenital anomalies; 16.7% had undescended testes (UDT),
      anorectal malformation (ARM) and patent processus vaginalis (PPV); and duplicate
      bladder occurred in 5.6% of the patients. All but one patient had bilateral
      posterior iliac osteotomy at bladder closure. Out of the 17 patients that had
      osteotomy, 76.5% had satisfactory bladder closure (no complication), 5.9% had
      superficial wound dehiscence, 11.8% had bladder neck dehiscence and 5.9% had
      complete disruption. The lone patient that did not undergo osteotomy had complete
      bladder dehiscence. Postoperative immobilization was done for 3 weeks for 16
      cases; one was discontinued after 1 week because of complication. The longest
      follow-up was for 2 years and the shortest for 2 weeks. Four patients (22.2%) did
      not turn up for follow-up. CONCLUSION: Exstrophy anomalies although rare remain a
      major challenge in paediatric surgery. Iliac osteotomy, among other technical
      considerations, remains a cornerstone for successful bladder closure.

PMID- 24309410
TI  - Type 2 diabetes mellitus and its risk factors among the rural Fulanis of Northern
      Nigeria.
AB  - BACKGROUND: Information about diabetes mellitus (DM) from the rural populations
      in Nigeria, particularly among the rural Fulanis is limited. MATERIALS AND
      METHODS: This was a cross-sectional study conducted in two rural districts of
      Sokoto State in Northern Nigeria. Using a modification of the WHO STEP wise
      approach to surveillance (STEPS) instrument, information on sociodemographic and
      anthropometric data was obtained. Either a casual or fasting plasma glucose (FPG)
      level was obtained in all subjects while oral glucose tolerance test was
      performed in a randomly selected group of 50 of the study participants. RESULTS:
      Three hundred and ninety-three subjects participated in the study. The prevalence
      rates of DM, impaired fasting glycemia (IFG), and impaired glucose tolerance
      (IGT) were 0.8, 6.9, and 8%, respectively. The mean (SD) FPG was higher in males
      (5.1 +/- 0.6 mmol/L) than in females (4.9 +/- 0.6 mmol/l), but not statistically
      significantly (P = 0.20). The major risk factors for DM among the rural Fulani
      were obesity and increasing age. CONCLUSION: The prevalence rates of DM and its
      principal risk factor obesity are low among the rural Nigerian Fulani. However,
      the prevalence of prediabetes is relatively high, a factor that may predispose to
      the future development of DM.

PMID- 24309411
TI  - A qualitative study of causes of prescribing errors among junior medical doctors
      in a Nigeria in-patient setting.
AB  - AIMS: The aims of this study were to identify and understand the factors
      underlying prescribing errors in order to determine how to prevent them.
      MATERIALS AND METHODS: A prospective qualitative study that involved face-to-face
      interviews and human factor analysis in a Tertiary Referral Hospital in Central
      Nigeria, from July 2011 to December 2011. Pharmacists in the study hospital
      prospectively reviewed prescription orders generated by doctors in selected wards
      (male and female medical, pediatric and the private wing wards) and identified
      prescribing errors. The 22 prescribers involved in the errors were interviewed,
      and given questionnaires to discover factors causing the errors. A model of human
      error theory was used to analyze the responses. RESULTS: Responses from the
      doctors suggest that most errors were made because of slips in attention. Lack of
      drug knowledge was not the single causative factor in any incident. Risk factors
      identified included individual, team, environment, and task factors. Junior
      doctors were affected by the prescribing habits of their seniors. Organizational
      factors identified included inadequate training/experience, absence of reference
      materials and absence of self-awareness of errors. Defenses against error such as
      other clinicians and guidelines were absent or deficient, and supervision was
      inadequate. CONCLUSIONS: To reduce the risk of prescribing errors, a number of
      strategies addressing individual, task, team, and environmental factors such as
      training of junior doctors, enforcing good practice in prescription writing,
      supervision, and reviewing the workload of junior doctors must be established.

PMID- 24309412
TI  - The role of polymerase chain reaction in early diagnosis of human
      immunodeficiency virus infection in infants.
AB  - BACKGROUND: The prevalence of human immunodeficiency virus (HIV) infection is
      rising in Sub- Saharan Africa. The various indirect tests readily available have
      not been helpful in neonatal and early infant diagnosis of the disease.
      Polymerase chain reaction (PCR) is a direct test that can be used in these groups
      of children. Early infant diagnosis is important in achieving good outcome in the
      management of HIV infection. The aim of this article was to examine the role of
      PCR in the evaluation HIV-infected infants, with a view to achieve early
      diagnosis, early treatment, and good outcome. MATERIALS AND METHODS: This was a
      prospective review of 174 infants delivered by HIV-infected mothers in a rural
      hospital from January 2007 to September 2008. The blood samples of the patients
      were collected and subjected to PCR analysis for detection of viral antigen. Two
      samples were collected, the first at 6 weeks and the second 6 weeks after that.
      The results were recorded, collated, and analyzed using SPSS version 17. RESULTS:
      There were 174 infants, 100 boys, and 74 girls. The age range was 6-8 weeks
      (median 6 weeks). PCR was positive for both the samples in 12 (6.9%) infants. PCR
      was negative in both samples in 162 (93.1%) infants. All infants who were
      negative in the first sampling were found to be negative in the second sampling
      as well. None of the infant was positive for only one sample. Analysis of 12
      positive infants revealed that 5 (2.9%) infants were placed on anti-retroviral
      drugs, 3 (1.7%) infants were not placed on anti-retroviral drugs because of low
      CD+ count, and 1 (1.0%) infant was lost to follow-up, while 3 (1.7%) infants died
      from sepsis. CONCLUSION: PCR has a role as a direct test in early diagnosis of
      HIV infection in infancy, particularly where the other direct test are not
      readily available.

PMID- 24309413
TI  - Childhood epilepsy in a tropical child psychiatric unit: challenges of providing
      care in a resource-constrained environment.
AB  - BACKGROUND: Epilepsy is an important cause of childhood morbidity and its care is
      fraught with challenges. Itinerant search for remedy and manifestation as or with
      psychiatric disorders could result in presentation in a psychiatric unit.
      Identification of these challenges is essential to providing optimal care. The
      objective was to identify caregiver challenges in the provision of care to
      children with epilepsy presenting in a psychiatric unit. MATERIALS AND METHOD:
      Administration of a structured questionnaire to caregivers of children with
      epilepsy presenting, between September and December 2011, in the newly
      constituted Child and Adolescent Mental Health(CAMH) Unit of the Federal
      NeuroPsychiatric Hospital, Kaduna Nigeria. RESULTS: A total of 84 caregivers were
      interviewed. The age range of the caregivers was 23 to 62 years (mean 38 +/- 9.2
      years) and a female preponderance (50, 59.5%). Most of the caregivers were in the
      upper social classes (I-III, 79.8%). A high number of challenges were indicated
      by majority 65, 77.4%) of the caregivers. The recurrence of seizures (84,100%)
      was the commonest challenge while the experience of discrimination (17, 20.2%)
      was the least. All caregivers had sought remedy from multiple health care
      options. Challenges were significantly (P < 0.05) associated with the female
      caregiver, age < 40 years, generalized type of epilepsy and residing outside
      Kaduna. CONCLUSION: The study identified multi dimensional caregiver challenges
      and highlighted the need for provision of comprehensive health and social
      services to children with epilepsy and their families.

PMID- 24309414
TI  - Supportive supervision: an effective intervention in achieving high quality
      malaria case management at primary health care level in Jos, Nigeria.
AB  - BACKGROUND: Supportive supervision is a form of supervision that promotes quality
      at all levels of health system by strengthening relationships within the system
      through prompt identification and resolution of problems among others. It is an
      effective intervention in improving health worker performance in low resource
      settings. Malaria is responsible for majority of outpatient consultations in
      Nigeria at all levels of care. MATERIALS AND METHODS: This was a facility-based
      interventional study with pre and post-intervention phases conducted among two
      groups.The study subjects were selected through a multistage sampling technique
      and data collection was done using both semistructured interviewer administered
      questionnaire and supervisory checklist. RESULTS: The mean knowledge scores of
      malaria within the intervention group showed an increase from 10.3 +/- 1.4 at
      preintervention to 11.3 +/- 1.5 at post-intervention (P < 0.0015). The proportion
      of respondents who correctly followed malaria management guidelines increased
      from 32.73% at first supervisory visit to 70.91% by the third supervisory visit
      (P < 0.001). An analysis of the supervisory checklist showed improvement in
      performance of healthcare workers with each supportive supervisory visit in most
      of the variables examined. CONCLUSIONS: This study has demonstrated that
      supportive supervision is a feasible and practicable tool in improving knowledge
      and practice of malaria case management among PHC workers.

PMID- 24309415
TI  - Successful pregnancy in one horn of a bicornuate uterus.
AB  - Normal development of the female reproductive tract involves a series of complex
      processes characterized by the differentiation, migration, fusion, and subsequent
      canalization of the Mullerian system. Uterine anomalies result when these
      processes are interrupted. Bicornuate uterus is a unification defect of the
      Mullerian ducts, and it is estimated to represent 10-39% of Mullerian duct
      anomalies. Pregnancies in bicornuate uterus are usually considered high-risk
      because of association with poor reproductive outcomes, such as pregnancy loss,
      preterm birth, malpresentations, and fetal deformity. Routine cervical cerclage
      and Strassman metroplasty have been advocated as treatment for this anomaly. We
      report a case of successful pregnancy in one of the horns of a bicornuate uterus
      managed in our unit. 

PMID- 24309416
TI  - Silicotuberculosis: importance of evaluation of serial radiographs.

PMID- 24309417
TI  - Epiploic appendagitis: an uncommon cause of acute abdomen.

PMID- 24309418
TI  - Epidemiology of Burkholderia multivorans strains obtained from non-cystic
      fibrosis patients isolated in large hospitals across the Czech Republic.

PMID- 24309419
TI  - Organizational culture and its implications for infection prevention and control
      in healthcare institutions.
AB  - BACKGROUND: It is not uncommon for infection prevention and control (IPC)
      interventions to be successful in one hospital yet fail, or have significantly
      less success, when implemented in another healthcare institution. Organizational
      factors have been postulated to be a major reason. As a result, there has been an
      increasing drive in recent years to understand and address organizational culture
      (OC) in order to achieve improved healthcare performance. AIM: To examine the
      inter-relationship between OC and behavioural attitudes by healthcare
      professionals; to determine whether and how OC may impact on IPC compliance; and
      to highlight the potential for OC modification interventions to improve IPC
      practices within hospitals. METHODS: Previous literature is reviewed and
      synthesized, using both IPC journals as well as publications focusing on human
      behaviour and organizational change. FINDINGS: The article evaluates the theory
      of OC within healthcare settings and identifies how various elements appear to
      impact on IPC-related behaviour. It highlights the paucity of well-designed
      studies but identifies sporadic literature suggesting that well-designed and
      customized OC change initiatives can have a positive impact on IPC practices,
      such as hand hygiene. CONCLUSION: OC change appears to be a promising, albeit
      challenging, target for IPC improvement campaigns - both from a theoretical
      perspective as well as from the results of the few available studies. However,
      more data and quality information are needed to identify effective strategies
      that can elicit effective and sustained change.

PMID- 24309420
TI  - Dimethocaine, a synthetic cocaine derivative: studies on its in vitro metabolism
      catalyzed by P450s and NAT2.
AB  - Dimethocaine (DMC), a synthetic derivative of cocaine, is distributed and
      consumed as "new psychoactive substance" (NPS) without any safety testing at the
      forefront. It is mainly metabolized by N-acetylation, N-deethylation or
      hydroxylation. Therefore, the aim of the presented study was to determine the
      human NAT and P450 isozymes involved in this major metabolic steps, to measure
      the kinetics of the reactions, and to estimate the contribution on in vivo
      hepatic clearance. For these studies, cDNA-expressed NATs and P450s were used and
      formation of metabolites after incubation was measured using LC-MS or LC-MS(n).
      For N-acetylation, NAT2 could be shown to be the only isoform catalyzing the
      reaction in vitro hence assuming to be the only relevant enzyme for in vivo
      acetylation. Kinetic profiles of all P450 catalyzed metabolite formations
      followed classic Michaelis-Menten behavior with enzyme affinities (Km values)
      between 3.6 and 220 MUM. Using the relative activity factor approach, the net
      clearances for deethylation of DMC were calculated to be 3% for P450 1A2, 1% for
      2C19, <1% for 2D6, and 96% for 3A4. The net clearances for hydroxylation of DMC
      were calculated to be 32% for P450 1A2, 5% for 2C19, 51% for 2D6, and 12% for
      3A4. Furthermore, these data were confirmed by chemical inhibition tests in human
      liver microsomes. As DMC is metabolized via two main steps and different P450
      isoforms were involved in the hepatic clearance of DMC, a clinically relevant
      interaction with single P450 inhibitors should not be expected. However, a slow
      acetylation phenotype or inhibition of NAT2 could lead to decreased N-acetylation
      and hence leading to an increased risk of side effects caused by this arylamine.

PMID- 24309421
TI  - Real-time identification of the evolution of conducting nano-filaments in TiO2
      thin film ReRAM.
AB  - Unipolar resistance switching (RS) in TiO2 thin films originates from the
      repeated formation and rupture of the Magneli phase conducting filaments through
      repeated nano-scale phase transitions. By applying the Johnson-Mehl-Avrami (JMA)
      type kinetic model to the careful analysis on the evolution of transient current
      in a pulse-switching, it was possible to elucidate the material specific
      evolution of the Magneli phase filament. This methodology was applied to the two
      types of TiO2 films grown by plasma-enhanced atomic layer deposition (PEALD) and
      sputtering. These two samples have structurally and electrically distinctive
      properties: PEALD film exhibited high variability in switching parameters and
      required an electroforming while sputtered film showed higher uniformity without
      distinct electroforming process. The JMA-type kinetic analysis of the RS
      behaviors revealed that the rejuvenation of the filament is accomplished by
      repeated one-dimensional nucleation followed by a two-dimensional growth in PEALD
      samples, whereas one-dimensional nucleation-free mechanism dominates in sputtered
      films. 

PMID- 24309422
TI  - Different circulating progesterone concentrations during synchronization of
      ovulation protocol did not affect ovarian follicular and pregnancy responses in
      seasonal anestrous buffalo cows.
AB  - Three experiments were designed to evaluate the effect of different circulating
      progesterone (P4) concentrations during synchronization of ovulation protocol for
      timed artificial insemination of seasonal anestrous buffalo cows. In the first
      trial, ovariectomized cows were randomly allocated into one of three groups:
      using new P4 devices (G-New; n = 8), using devices previously used for 9 days (G
      Used1x; n = 8), and using devices previously used for 18 days (G-Used2x; n = 8).
      The P4 device was maintained for 9 days, and the circulating P4 concentration was
      measured daily. The circulating P4 concentrations during the P4 device treatment
      were the lowest for G-Used2x (1.10 +/- 0.04 ng/mL), intermediate for G-Used1x
      (1.52 +/- 0.05 ng/mL), and the highest for G-New (2.47 +/- 0.07 ng/mL; P =
      0.001). In the second trial, 31 anestrous cows had their ovarian follicular
      dynamics evaluated after receiving the treatments described previously (G-New [n
      = 10], G-Used1x [n = 11], and G-Used2x [n = 10]). At insertion of the P4 device,
      cows were administered 2.0 mg of estradiol benzoate. Nine days later, the P4
      device was removed and cows were administered 0.53 mg of cloprostenol sodium plus
      400 IU of eCG. Forty-eight hours after P4 device removal, 10 MUg of buserelin
      acetate was administered. There were no differences among the groups (G-New vs. G
      Used1x vs. G-Used2x) in diameter of the largest follicle at P4 device removal
      (9.0 +/- 0.8 vs. 10.1 +/- 0.9 vs. 8.6 +/- 0.8 mm; P = 0.35), in interval from P4
      device removal to ovulation (77.1 +/- 4.5 vs. 76.5 +/- 4.7 vs. 74.0 +/- 4.4
      hours; P = 0.31), or in ovulation rate (80.0% vs. 81.8% vs. 60.0%; P = 0.51). In
      experiment 3, 350 anestrous cows were randomly assigned into one of the three
      treatments described previously (G-New, n = 111; G-Used1x, n = 121; G-Used2x, n =
      118) and received a timed artificial insemination for 16 hours after buserelin
      treatment. The 30-day pregnancy rates did not differ among groups (55.9% vs.
      55.4% vs. 48.3%; P = 0.39). Thus, the low circulating P4 concentrations released
      from a used P4 device efficiently control the ovarian follicular growth and had
      no detrimental effect on the pregnancy rates of the seasonal anestrous buffalo
      cows.

PMID- 24309424
TI  - Land-cover effects on soil organic carbon stocks in a European city.
AB  - Soil is the vital foundation of terrestrial ecosystems storing water, nutrients,
      and almost three-quarters of the organic carbon stocks of the Earth's biomes.
      Soil organic carbon (SOC) stocks vary with land-cover and land-use change, with
      significant losses occurring through disturbance and cultivation. Although
      urbanisation is a growing contributor to land-use change globally, the effects of
      urban land-cover types on SOC stocks have not been studied for densely built
      cities. Additionally, there is a need to resolve the direction and extent to
      which greenspace management such as tree planting impacts on SOC concentrations.
      Here, we analyse the effect of land-cover (herbaceous, shrub or tree cover), on
      SOC stocks in domestic gardens and non-domestic greenspaces across a typical mid
      sized U.K. city (Leicester, 73 km(2), 56% greenspace), and map citywide
      distribution of this ecosystem service. SOC was measured in topsoil and compared
      to surrounding extra-urban agricultural land. Average SOC storage in the city's
      greenspace was 9.9 kg m(-2), to 21 cm depth. SOC concentrations under trees and
      shrubs in domestic gardens were greater than all other land-covers, with total
      median storage of 13.5 kg m(-2) to 21 cm depth, more than 3 kg m(-2) greater than
      any other land-cover class in domestic and non-domestic greenspace and 5 kg m(-2)
      greater than in arable land. Land-cover did not significantly affect SOC
      concentrations in non-domestic greenspace, but values beneath trees were higher
      than under both pasture and arable land, whereas concentrations under shrub and
      herbaceous land-covers were only higher than arable fields. We conclude that
      although differences in greenspace management affect SOC stocks, trees only
      marginally increase these stocks in non-domestic greenspaces, but may enhance
      them in domestic gardens, and greenspace topsoils hold substantial SOC stores
      that require protection from further expansion of artificial surfaces e.g. patios
      and driveways.

PMID- 24309423
TI  - Genomic analyses of RH alleles to improve transfusion therapy in patients with
      sickle cell disease.
AB  - BACKGROUND: Red cell (RBC) blood group alloimmunization remains a major problem
      in transfusion medicine. Patients with sickle cell disease (SCD) are at
      particularly high risk for developing alloantibodies to RBC antigens compared to
      other multiply transfused patient populations. Hemagglutination is the classical
      method used to test for blood group antigens, but depending on the typing methods
      and reagents used may result in discrepancies that preclude interpretation based
      on serologic reactivity alone. Molecular methods, including customized DNA
      microarrays, are increasingly used to complement serologic methods in predicting
      blood type. The purpose of this study was to determine the diversity and
      frequency of RH alleles in African Americans and to assess the performance of a
      DNA microarray for RH allele determination. MATERIAL AND METHODS: Two sets of
      samples were tested: (i) individuals with known variant Rh types and (ii)
      randomly selected African American donors and patients with SCD. Standard
      hemagglutination tests were used to establish the Rh phenotype, and cDNA- and
      gDNA-based analyses (sequencing, PCR-RFLP, and customized RHD and RHCE
      microarrays were used to predict the genotype). RESULTS: In a total of 829
      samples (1658 alleles), 72 different alleles (40 RHD and 32 RHCE) were
      identified, 22 of which are novel. DNA microarrays detected all nucleotides
      probed, allowing for characterization of over 900 alleles. CONCLUSIONS: High
      throughput DNA testing platforms provide a means to test a relatively large
      number of donors and potentially prevent immunization by changing the way antigen
      negative blood is provided to patients. Because of the high RH allelic diversity
      found in the African American population, determination of an accurate Rh
      phenotype often requires DNA testing, in conjunction with serologic testing.
      Allele-specific microarrays offer a means to perform high-throughput donor Rh
      typing and serve as a valuable adjunct to serologic methods to predict Rh type.
      Because DNA microarrays test for only a fixed panel of allelic polymorphisms and
      cannot determine haplotype phase, alternative methods such as Next Generation
      Sequencing hold the greatest potential to accurately characterize blood group
      phenotypes and ameliorate the clinical course of multiply-transfused patients
      with sickle cell disease.

PMID- 24309425
TI  - Perception of transgenerational family relationships: comparison of eating
      disordered patients and their parents.
AB  - BACKGROUND: Disturbances in various elements of transgenerational family
      functioning patterns are not uncommon in studies of eating disorders. We examined
      the relationship between patients' perception of autonomy and intimacy in their
      families of origin and that of their parents in their own families of origin.
      MATERIAL AND METHODS: The sample consisted of 112 girls who had a diagnosis of an
      eating disorder and their parents; 54 of the girls were diagnosed with anorexia
      nervosa restrictive subtype, 22 as anorexia nervosa binge/purge subtype, and 36
      were diagnosed with bulimia nervosa. We had 2 control groups: 1 group consisted
      of 36 girls diagnosed with a depressive episode, dysthymia, or adjustment
      disorder with depressed mood and the other group was 85 female students from
      schools in Cracow, Poland and their parents. We used the the Family of Origin
      Scale to assess perception of family relationships. Statistical analysis was
      performed with the Statistical Package for the Social Sciences (SPSS 20.0.PL;
      Chicago, IL, USA). RESULTS: There was a significant association between
      daughters' and fathers' perceptions of autonomy in their families of origin in
      all groups. There was no significant association between daughters' and mothers'
      perceptions in all groups. The strongest correlation was between the non-clinical
      sample of girls and their fathers and for the bulimic group. CONCLUSIONS: We did
      not detect any link indicating the specificity of transgenerational transmission
      of autonomy and intimacy in eating disorders. The results point to the importance
      of the father figure in studies of family systems, including the context of
      family transmission.

PMID- 24309426
TI  - STING-dependent cytosolic DNA sensing pathways.
AB  - STING (STimulator of INterferon Genes) has recently been identified as being
      essential for controlling host defense countermeasures triggered by microbial
      cytosolic DNA and subsequently cyclic dinucleotides (CDNs). However, chronic
      STING activation may also be responsible for initiating certain inflammatory
      diseases manifested by self DNA. Recent studies have also revealed a key role for
      cyclic GMP-AMP synthase (cGAS) in STING activation. Although a full understanding
      of the mechanisms of STING activation requires further studies, new insights into
      STING function afford the opportunity of designing novel compounds aimed at
      facilitating vaccine development or new therapies for the treatment of
      inflammatory disease. 

PMID- 24309427
TI  - Enhancement of antibody production against rabies virus by uridine 5'
      triphosphate in mice.
AB  - Extracellular nucleotides such as adenosine 5'-triphospate (ATP) and uridine 5'
      triphosphate (UTP) interact with P2 purinergic receptors on the surface of
      phagocytic cells and induce various physiological reactions. In this study, the
      production of antibody in mice immunized with an inactivated rabies vaccine
      containing these nucleotides was investigated. Injection of inactivated rabies
      vaccine with UTP, but not with ATP, induced significantly higher serum antibody
      production in mice. The enhancement of antibody production by UTP was inhibited
      by an anti-P2Y4 receptor antibody. In an air pouch experiment, UTP treatment
      increased the number of monocytes and macrophages infiltrating the pouch and up
      regulated the gene expression of IL-4 and IL-13 in the regional lymph nodes.
      These results suggested that UTP admixed with rabies vaccine activates Th2 cells
      and induces a humoral immune response. Furthermore, the survival rate of mice
      immunized with a rabies vaccine admixed with UTP before rabies virus challenge
      was slightly higher than that of control mice. In conclusion, UTP can act as a
      vaccine adjuvant to enhance antibody production against the rabies virus in mice.

PMID- 24309429
TI  - Cardiovascular health in US adolescents: far from ideal.

PMID- 24309430
TI  - 20 things you didn't know about electrocardiography.

PMID- 24309431
TI  - Summaries of nursing care-related systematic reviews from the Cochrane Library:
      pharmacotherapy for mild hypertension.

PMID- 24309432
TI  - Beyond NIMBYism: understanding community antipathy toward needle distribution
      services.
AB  - In late 2007 the Homeless Youth Alliance (HYA), a small non-profit serving
      homeless youth in the Haight-Ashbury neighbourhood of San Francisco, USA,
      attempted to move its needle exchange service from a site on the Haight street
      commercial strip to a community centre approximately 150m away. The reaction of
      the housed community in the area was vocal and organized, and attracted
      considerable regional media attention. Ultimately, the plan to move the service
      had to be cancelled. The authors were, respectively, board chair and executive
      director of HYA at the time, and collected extensive field notes and media
      records as events unfolded. In this paper, we re-examine these events through
      literatures on contested spaces and on 'Not In My Backyard' (NIMBY) resistance to
      social services. We found that opposition to the service relocation had little to
      do with opposition to needle exchange itself, but rather was symptomatic of
      broader contestation over the identity and character of the neighbourhood. On the
      one hand, the neighbourhood had experienced skyrocketing housing prices over the
      past 40 years, making home ownership almost exclusively the province of the
      wealthy. On the other, the neighbourhood retains historic connections to the 1968
      'Summer of Love', and the main commercial strip forms the centre of an active
      injecting drug use scene. As a consequence, many home owners who felt they had
      made considerable sacrifices to afford to live in the area expressed a sense of
      being "under siege" from drug users, and also believed that the City government
      pursues a deliberate policy of "keeping the Haight weird" by supporting ongoing
      service provision to drug users in the area. Housed residents responded to this
      situation in a variety of ways. One response was to engage in what we term
      'defensive place making', in which a small part of a broader neighbourhood is
      reimagined as "a different neighbourhood". HYA's attempt to move from its current
      location to this 'different neighbourhood' was thus perceived as an "invasion"
      which threatened to break down a tentatively established separate identity. We
      conclude with a discussion of the relevance of these events for understanding and
      mitigating community opposition to services for drug users elsewhere. 

PMID- 24309433
TI  - Adaptive strong-field control of chemical dynamics guided by three-dimensional
      momentum imaging.
AB  - Shaping ultrafast laser pulses using adaptive feedback can manipulate dynamics in
      molecular systems, but extracting information from the optimized pulse remains
      difficult. Experimental time constraints often limit feedback to a single
      observable, complicating efforts to decipher the underlying mechanisms and
      parameterize the search process. Here we show, using two strong-field examples,
      that by rapidly inverting velocity map images of ions to recover the three
      dimensional photofragment momentum distribution and incorporating that feedback
      into the control loop, the specificity of the control objective is markedly
      increased. First, the complex angular distribution of fragment ions from the
      nomega+C2D4->C2D3++D interaction is manipulated. Second, isomerization of
      acetylene (nomega+C2H2->C2H2(2+)->CH2++C+) is controlled via a barrier
      suppression mechanism, a result that is validated by model calculations.
      Collectively, these experiments comprise a significant advance towards the
      fundamental goal of actively guiding population to a specified quantum state of a
      molecule.

PMID- 24309434
TI  - Zero-order ultrasensitivity: a study of criticality and fluctuations under the
      total quasi-steady state approximation in the linear noise regime.
AB  - Zero-order ultrasensitivity (ZOU) is a long known and interesting phenomenon in
      enzyme networks. Here, a substrate is reversibly modified by two antagonistic
      enzymes (a 'push-pull' system) and the fraction in modified state undergoes a
      sharp switching from near-zero to near-unity at a critical value of the ratio of
      the enzyme concentrations, under saturation conditions. ZOU and its extensions
      have been studied for several decades now, ever since the seminal paper of
      Goldbeter and Koshland (1981); however, a complete probabilistic treatment,
      important for the study of fluctuations in finite populations, is still lacking.
      In this paper, we study ZOU using a modular approach, akin to the total quasi
      steady state approximation (tQSSA). This approach leads to a set of Fokker-Planck
      (drift-diffusion) equations for the probability distributions of the intermediate
      enzyme-bound complexes, as well as the modified/unmodified fractions of substrate
      molecules. We obtain explicit expressions for various average fractions and their
      fluctuations in the linear noise approximation (LNA). The emergence of a
      'critical point' for the switching transition is rigorously established. New
      analytical results are derived for the average and variance of the fractional
      substrate concentration in various chemical states in the near-critical regime.
      For the total fraction in the modified state, the variance is shown to be a
      maximum near the critical point and decays algebraically away from it, similar to
      a second-order phase transition. The new analytical results are compared with
      existing ones as well as detailed numerical simulations using a Gillespie
      algorithm. 

PMID- 24309435
TI  - Bifunctional capsular dosage form: novel fanicular cylindrical gastroretentive
      system of clarithromycin and immediate release granules of ranitidine HCl for
      simultaneous delivery.
AB  - The study was aimed to develop a bifunctional single unit capsular system
      containing gastroretentive funicular cylindrical system (FCS) for controlled
      local delivery of clarithromycin and immediate release of ranitidine HCl. A 2(3)
      full factorial design was used to prepare gastroretentive FCS of clarithromycin
      using polyacrylamide (PAM), HPMC E15LV and Carbopol 934 P. The FCSs were
      evaluated for % cumulative drug release, floating time and in vitro detachment
      stress. Among the eight formulations, FCS5 (containing PAM and Carbopol 934 P at
      high and HPMC E15LV at low levels) showed % cumulative drug release of 97.09+/
      1.14% in 8 h, floating time of 3 h and detachment stress of 8303.64+/-0.34
      dynes/cm(2). Evaluation of optimized FCS by novel dynamic in vitro test proved
      superior bioadhesivity than cylindrical system under aggressive simulated
      peristaltic activity. Magnetic resonance imaging elucidated zero order release
      via constant swelling and erosion of FCS5. In vitro permeability across gastric
      mucin ensured its potential for effective eradication of deep seated Helicobactor
      pylori in gastric linings. The optimized FCS was combined with immediate release
      granules of rantidine HCl to get a bifunctional capsular dosage form. In vitro
      simultaneous drug release of clarithromycin and rantidine estimated by Vierordt's
      method exhibited a controlled drug release of 97.72+/-0.4% in 8 h for
      clarithromycin through FCS5 and 98.8+/-1.2% in 60 min from IR granules of
      ranitidine HCl. The novel system thus established its capability of simultaneous
      variable delivery of acid suppression agent and macrolide antibiotic that can be
      advantageous in clinical setting.

PMID- 24309438
TI  - Non-pharmacological treatment options for refractory epilepsy: an overview of
      human treatment modalities and their potential utility in dogs.
AB  - Refractory epilepsy is a common disorder both in humans and dogs and treatment
      protocols are difficult to optimise. In humans, different non-pharmacological
      treatment modalities currently available include surgery, the ketogenic diet and
      neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients,
      but requires strict patient selection. The ketogenic diet is indicated in severe
      childhood epilepsies, but efficacy is limited and long-term compliance can be
      problematic. In the past decade, various types of neurostimulation have emerged
      as promising treatment modalities for humans with refractory epilepsy. Currently,
      none of these treatment options are used in routine daily clinical practice to
      treat dogs with the condition. Since many dogs with poorly controlled seizures do
      not survive, the search for alternative treatment options for canine refractory
      epilepsy should be prioritised. This review provides an overview of non
      pharmacological treatment options for human refractory epilepsy. The current
      knowledge and limitations of these treatments in canine refractory epilepsy is
      also discussed. 

PMID- 24309437
TI  - Transcriptional control of DNA replication licensing by Myc.
AB  - The c-myc protooncogene encodes the Myc transcription factor, a global regulator
      of fundamental cellular processes. Deregulation of c-myc leads to tumorigenesis,
      and c-myc is an important driver in human cancer. Myc and its dimerization
      partner Max are bHLH-Zip DNA binding proteins involved in transcriptional
      regulation of target genes. Non-transcriptional functions have also been
      attributed to the Myc protein, notably direct interaction with the pre
      replicative complex (pre-RC) controlling the initiation of DNA replication. A key
      component of the pre-RC is the Cdt1 protein, an essential factor in origin
      licensing. Here we present data suggesting that the CDT1 gene is a
      transcriptional target of the Myc-Max complex. Expression of the CDT1 gene in v
      myc-transformed cells directly correlates with myc expression. Also, human tumor
      cells with elevated c-myc expression display increased CDT1 expression.
      Occupation of the CDT1 promoter by Myc-Max is demonstrated by chromatin
      immunoprecipitation, and transactivation by Myc-Max is shown in reporter assays.
      Ectopic expression of CDT1 leads to cell transformation. Our results provide a
      possible direct mechanistic link of Myc's canonical function as a transcription
      factor to DNA replication. Furthermore, we suggest that aberrant transcriptional
      activation of CDT1 by deregulated myc alleles contributes to the genomic
      instabilities observed in tumor cells. 

PMID- 24309439
TI  - Prediction of the compression ratio for municipal solid waste using decision
      tree.
AB  - The compression ratio of municipal solid waste (MSW) is an essential parameter
      for evaluation of waste settlement and landfill design. However, no appropriate
      model has been proposed to estimate the waste compression ratio so far. In this
      study, a decision tree method was utilized to predict the waste compression ratio
      (C'c). The tree was constructed using Quinlan's M5 algorithm. A reliable database
      retrieved from the literature was used to develop a practical model that relates
      C'c to waste composition and properties, including dry density, dry weight water
      content, and percentage of biodegradable organic waste using the decision tree
      method. The performance of the developed model was examined in terms of different
      statistical criteria, including correlation coefficient, root mean squared error,
      mean absolute error and mean bias error, recommended by researchers. The obtained
      results demonstrate that the suggested model is able to evaluate the compression
      ratio of MSW effectively. 

PMID- 24309436
TI  - Dentin biomodification: strategies, renewable resources and clinical
      applications.
AB  - OBJECTIVES: The biomodification of dentin is a biomimetic approach, mediated by
      bioactive agents, to enhance and reinforce the dentin by locally altering the
      biochemistry and biomechanical properties. This review provides an overview of
      key dentin matrix components, targeting effects of biomodification strategies,
      the chemistry of renewable natural sources, and current research on their
      potential clinical applications. METHODS: The PubMed database and collected
      literature were used as a resource for peer-reviewed articles to highlight the
      topics of dentin hierarchical structure, biomodification agents, and laboratorial
      investigations of their clinical applications. In addition, new data is presented
      on laboratorial methods for the standardization of proanthocyanidin-rich
      preparations as a renewable source of plant-derived biomodification agents.
      RESULTS: Biomodification agents can be categorized as physical methods and
      chemical agents. Synthetic and naturally occurring chemical strategies present
      distinctive mechanism of interaction with the tissue. Initially thought to be
      driven only by inter- or intra-molecular collagen induced non-enzymatic cross
      linking, multiple interactions with other dentin components are fundamental for
      the long-term biomechanics and biostability of the tissue. Oligomeric
      proanthocyanidins show promising bioactivity, and their chemical complexity
      requires systematic evaluation of the active compounds to produce a fully
      standardized intervention material from renewable resource, prior to their
      detailed clinical evaluation. SIGNIFICANCE: Understanding the hierarchical
      structure of dentin and the targeting effect of the bioactive compounds will
      establish their use in both dentin-biomaterials interface and caries management.

PMID- 24309440
TI  - DNA strand-displacement-induced fluorescence enhancement for highly sensitive and
      selective assay of multiple microRNA in cancer cells.
AB  - We report a new strategy for evaluating multiple miRNA expressions in cancer
      cells based on DNA strand-displacement-induced fluorescence enhancement. This
      assay has the ability to discriminate the target from even single-base mismatched
      sequences or other miRNAs. 

PMID- 24309441
TI  - Recent characteristics and outcomes of Japanese stable angina pectoris after
      percutaneous coronary intervention. An observational cohort study using the
      Shinken Database.
AB  - The mortality and morbidity of patients with stable angina pectoris (SAP) after
      percutaneous coronary intervention (PCI) in Japan differ from those in Western
      countries, although Japanese data are limited. We selected from the Shinken
      Database a single-hospital-based cohort of Japanese patients (n = 15,227) who
      visited The Cardiovascular Institute between 2004 and 2010 to undergo PCI. We
      followed-up the patients after PCI. A major adverse cardiac event (MACE) was
      defined as composite endpoints including all-cause death, acute myocardial
      infarction (AMI), and target-lesion revascularization (TLR). This study included
      747 SAP patients (median follow-up period, 1,000 +/- 703 days). The all cause
      mortality rate in SAP was 1.3% at 1 year, 2.7% at 3 years, and 6.1% at 5 years.
      The AMI rate was 0.5% at 1 year, 1.1% at 3 years, and 3.0% at 5 years, and the
      MACE rate was 14.0% at 1 year, 17.6% at 3 years, and 25.6% at 5 years. Moreover,
      new lesion PCI and heart failure admission continued to occur beyond 1 year after
      PCI without attenuation of their annual incidences up to 5 years. Multivariate
      analysis showed that poor left ventricular ejection fraction, chronic kidney
      disease (CKD), and absence of statin treatment were independent predictors of all
      cause death of SAP patients after PCI. The results of the present study revealed
      the characteristics and long-term outcomes of Japanese SAP patients after PCI.
      The results of the present study suggest cardiorenal interaction and statin
      treatment play important roles in the long-term outcomes of Japanese CAD patients
      treated by PCI.

PMID- 24309442
TI  - Neointimal calcification after stenting and chronic kidney disease.
AB  - The timing and incidence of neointimal calcification after stenting (NIC) is
      largely unknown. The purpose of our study was to elucidate the characteristics of
      NIC. The presence of NIC in patients who underwent intravascular ultrasound
      between June 30, 2009 and June 30, 2012 was analyzed. The patients were divided
      into two groups based on the follow-up period: < 365 days or >= 365 days. A total
      of 181 images were analyzed. Those with NIC had a lower estimated glomerular
      filtration rate [51 (6-60) versus 61 (52-72) mL/minute/1.73 m2; P < 0.01] and
      longer time after stenting [3198 (1710-3684) versus 211 (180-516) days; P < 0.01]
      compared to those without NIC. NIC during short-term follow-up was observed only
      in patients who were on hemodialysis. On the other hand, NIC in the long-term
      follow-up was observed only in patients with bare metal stents. The development
      of NIC was related to renal function and time after stenting. NIC in the short
      term and the long-term follow-up was observed only in patients who were on
      hemodialysis and who were implanted with a bare metal stent, respectively.

PMID- 24309443
TI  - Localization of native high-density lipoprotein and its relation to plaque
      morphology in human coronary artery.
AB  - High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport,
      and halts the progression of atherosclerosis. However, its localization in human
      vascular wall is not well understood. We discovered that by exciting at 470-nm
      and emitting at 515-nm light wavelengths, Fast green dye (FG) elicits brown
      fluorescence characteristic of HDL only. Therefore, the localization of native
      HDL in normal segments and plaques in excised human coronary artery was
      investigated by scanning their transected surface with color fluorescent
      microscopy (CFM) using FG as a biomarker, and the relationships between the
      localization of HDL and morphology of plaques and normal segments classified by
      conventional angioscopy and histology were examined. The % incidence of HDL in 13
      normal segments (NS) with thin (<= 200 um) intima, 28 NS with thick (200 um <)
      intima, 41 white plaques (early stage of plaque growth), 15 yellow plaques (Y)
      without necrotic core (NC), and 20 Y with NC (advanced stage of plaque growth),
      was 30, 71 (P < 0.05 versus NS with thin intima and Y with NC), 83 (P < 0.05
      versus NS with thin intima and Y with NC), 60, and 35, respectively. HDL begins
      to deposit in human coronary arterial wall in the early stage of atherosclerosis
      and deposits increase with plaque growth, but HDL decreases in plaques at an
      advanced stage of growth.

PMID- 24309444
TI  - Aortic valve calcium score is associated with coronary calcified plaque burden.
AB  - The aim of this study was to investigate the association between the aortic valve
      calcium score (AVCS) and the coronary plaque burden using 64-slice multi-detector
      computed tomography (MDCT). Calcification of the aortic valve without significant
      aortic stenosis itself has been suggested to be a marker of atherosclerosis. In
      this study, we attempted to identify a quantitative correlation between AVCS and
      the coronary plaque burden assumed by the Gensini score. We retrospectively
      evaluated 200 patients (aged 40 - 88 years) who underwent MDCT and coronary
      angiography for chest pain. After exclusion of an aortic stenosis (peak velocity
      >= 2.0 m/s), the plaque burden of the coronary artery was determined by the
      Gensini score based on the plaque composition (calcified, mixed, or noncalcified
      plaque) of the CT angiogram. The calcific aortic valve group (AVCS > 0) showed no
      significant difference in the total plaque burden compared to the noncalcific
      aortic valve group (AVC = 0) (Gensini score 23.6 +/- 15.1 versus 21.2 +/- 17.5, P
      = 0.31). However, the calcified plaque burden was higher in the calcific aortic
      valve group (Gensini score by calcified plaque 9.1 +/- 10.4 versus 5.5 +/- 8.6, P
      = 0.008). In the subgroup of patients who had an AVCS of more than 90.0 (upper
      75th percentile, n = 20), the AVCS showed a more significant correlation with the
      Gensini score by calcified plaque (r = 0.618, P < 0.01). Our results suggest that
      a high level of AVCS is associated with the calcified plaque burden of the
      coronary artery rather than the total plaque burden. 

PMID- 24309445
TI  - Usefulness of a simple prognostication score in prediction of the prognoses of
      patients with out-of-hospital cardiac arrests.
AB  - Sudden cardiac death is a serious problem in public health but the overall
      survival rate of out-of-hospital cardiac arrests (OHCAs) remains low. In this
      study, we identified clinical parameters to predict the prognosis of OHCA
      patients and proposed a simple prognostication score for prediction of their
      prognoses. The study population consisted of 750 consecutive patients with OHCAs
      of internal cause who were transported to our institute from July 2008 to June
      2010. They were divided into survivors and nonsurvivors, and clinical parameters
      were compared between them to detect significant parameters for prediction of
      their prognoses. The population of those who survived at 1 month numbered 34.
      Multivariate analysis exhibited 10 independent predictive factors of survival,
      which included witnessed cardiac arrest and bystander-initiated CPR. When the
      prognostication score was calculated from these independent predictive factors, a
      score of >= 6 points indicated survival with a sensitivity of 88.6% and a
      specificity of 97.6%. When the patients were divided into younger and older
      populations with a threshold of 70 years, these values were 94.1% and 96.1% in
      younger but 70.0% and 98.4% in older patients, respectively. In retrospective
      observation, a simple prognostication score was useful to predict patient
      prognoses in OHCAs, but its usefulness was limited in an older population.

PMID- 24309446
TI  - Prophylactic statin administration may prevent shortening of the fibrillation
      cycle length in patients with new-onset atrial fibrillation.
AB  - Patients with recently diagnosed atrial fibrillation (AF) tend to exhibit a
      longer fibrillation cycle length (FCL) than those having a longer clinical
      history. However, the electrophysiological properties of new-onset AF may vary
      because of the clinical background of patients. In this study, we evaluated
      clinical factors to identify the determinants of FCL in new-onset AF.
      Electrocardiograms (ECGs) recorded from 2008 through 2011 were analyzed using our
      digital ECG-profiling system. In the 1,578 AF episodes recorded, 466 new-onset AF
      episodes were identified using clinical referral history and previous ECGs. After
      evaluating FCL in these new-onset AF episodes, using a customized fibrillation
      wave analyzer with fast Fourier transform analysis, we divided the patients into
      a longer-FCL group and a shorter-FCL group using the median FCL (158 ms).
      Propensity score matching yielded 135 matched pairs of patients with comparable
      mean ages between the two groups. Four factors (brain natriuretic peptide levels,
      and use of angiotensin receptor blockers, calcium channel blockers or statins)
      exhibited a significant difference between the two groups. Multivariate analysis
      revealed that statin use was the only significant independent predictor of longer
      FCL (Odds ratio, 3.86; 95% CI, 1.659.63; P = 0.003). Among various clinical
      parameters, statin use was related to longer FCL at the time of new-onset AF in
      patients with AF.

PMID- 24309447
TI  - Tolvaptan can improve clinical course in responders.
AB  - We previously defined "responders" as patients with increases in urine volume
      (UV) on day 1 after the administration of tolvaptan (TLV), and demonstrated that
      responders to TLV could be predicted with considerable accuracy by urine
      osmolality (U-OSM) levels. Responders and non-responders to TLV should be
      associated with different clinical courses after a certain time following TLV
      administration. Therefore, the aim of the present study was to validate our
      definition of responders by clinical parameters 1 week after administration of
      TLV. Data (n = 85) were obtained from in hospital patients with decompensated
      heart failure (HF) who had received TLV at 3.75-15 mg daily, and clinical data at
      1 week after the administration of TLV were compared with those of baseline.
      Sixty patients (70.6%) were "responders", in whom UV on day 1 increased after the
      administration of TLV compared with day 0. "Non-responders" were older, and had
      higher serum creatinine concentration and lower baseline U-OSM than "responders".
      Serum creatinine concentration increased significantly in "non-responders", but
      was unchanged in "responders". Body weight, plasma B-type natriuretic peptide
      concentration, and HF symptom score decreased significantly in "responders", but
      remained unchanged in "non-responders". Increases in UV after the first
      administration of TLV were closely correlated with improvement of congestive HF
      after 1 week of TLV treatment, which verified our definition of "responders" to
      TLV.

PMID- 24309448
TI  - Insufficient self-care is an independent risk factor for adverse clinical
      outcomes in Japanese patients with heart failure.
AB  - Self-care is a cornerstone for the successful management of heart failure (HF).
      The purpose of this study was to examine the impacts of HF self-care on prognosis
      in Japanese patients with HF. A total of 283 HF outpatients (age 64 +/- 14, 70%
      male, 52% HFrEF) were enrolled. We asked patients to answer about their adhevence
      to 5 self-care behaviors (medication, eating a low-sodium diet, regular exercise,
      daily weight check, and treatment seeking behavior). On the basis of the results,
      we classified patients into a good self-care group and a poor self-care group.
      The primary outcome was HF hospitalization and/or cardiac death. In total, 65% of
      patients were classified into the poor self-care group. During a median follow-up
      of 2 years, cardiac events occurred more frequently in the poor self-care group
      (22% versus 9.6%, P = 0.013). Poor self-care was an independent risk factor for
      cardiac events in Cox regression analysis adjusted for clinical parameters
      (hazard ratio = 2.86, P = 0.005). Poor self-care was also associated with an
      increased number of HF hospitalizations as well as an extended length of hospital
      stay for HF. Poor knowledge about HF was an independent determinant for poor self
      care in multivariate logistic regression analysis (odds ratio = 0.92, P = 0.019).
      Insufficient self-care is an independent risk factor for cardiac events in
      Japanese patients with HF.

PMID- 24309449
TI  - Diuretics and ultrafiltration in acute heart failure syndrome.
AB  - The use of diuretics and ultrafiltration in acute heart failure syndrome (AHFS)
      has been investigated in a number of randomized controlled trials (RCTs).
      However, the benefits have been variable. We therefore performed a meta-analysis
      to examine the overall effect of all-cause mortality, rehospitalization, renal
      function, dyspnea relief, and adverse events in patients with AHFS. We identified
      RCTs by a systematic search of MEDLINE, EMBASE, and the Cochrane Controlled
      Clinical Trials Register Database. Eligible RCTs were those that enrolled
      patients with AHFS and involved comparison of diuretic versus ultrafiltration
      therapy. Five RCTs with a total of nearly 500 patients were included. Overall,
      ultrafiltration therapy was not associated with significantly decreased risk of
      all-cause mortality (relative risk [RR], 0.977; 95% confidence interval [CI],
      0.602 to 1.587; P = 0.925; I2 = 0.0%), rehospitalization (RR, 0.903; 95% CI,
      0.696 to 1.170; P = 0.440; I2 = 77.4%), dyspnea score (weighted mean difference
      [WMD], 0.168; 95% CI, -0.318 to 0.653; P = 0.498; I2 = 11.4%) and creatinine
      (WMD, 0.055 mg/mL; 95% CI, -0.101 to 0.210; P = 0.491; I2 = 48.4%). However,
      there was significantly more weight loss (WMD, 1.333 kg; 95% CI, 0.186 to 2.479;
      P = 0.023; I2 = 57.7%) and net fluid removal (WMD, 1459.432 mL; 95% CI, 275.911
      to 2642.953; P = 0.016; I2 = 25.2%) in the ultrafiltration-therapy group. There
      was no significant difference in the risk of adverse events between the two
      groups. Compared with diuretic therapy, ultrafiltration produces greater weight
      loss and net fluid removal in a safe and effective manner.

PMID- 24309450
TI  - Can we obtain a noninvasive and continuous estimation of cardiac output?
      Comparison between three noninvasive methods.
AB  - Cardiac output (CO) is often desirable for assessing the hemodynamic condition of
      a patient, especially in critically ill cardiac patients. Various noninvasive
      methods are available for this purpose. Inert gas rebreathing (IGR) and 2D
      Doppler echocardiography methods have been validated. Based on the relationship
      between pulse wave transit time and stroke volume, the VISMO(r) provides an
      estimated continuous cardiac output (esCCO) measurement using only an
      electrocardiogram, pulse oximeter wave, and cuff arterial blood pressure. Doppler
      echocardiography is being currently used in every day practice in this setting
      and IGR is a validated method, thus we wanted to assess the agreement between
      these 3 methods for noninvasive CO calculation and reproducibility of esCCO.
      Patients followed in our cardiology department received on the same day a CO
      analysis by esCCO, Doppler echocardiography and IGR. Thirty-four patients were
      included (16 women, mean age 65 +/- 15 years). Bland and Altman plots showed a
      good agreement between IGR and 2D-Doppler echocardiography (bias = 0.31
      L/minute). Though there was also an agreement between esCCO and the other 2, the
      bias was rather large: 1.18 L/minute with IGR and 1.51 L/min with 2D-Doppler
      echo. The intraclass correlation coefficient was poor whatever the methods.
      However, esCCO had a satisfactory reproducibility and accuracy compared rather
      well with the other 2. This method could be suitable for patient screening and
      monitoring.

PMID- 24309451
TI  - Risk model of cardiovascular surgery in 845 Marfan patients using the Japan adult
      cardiovascular surgery database.
AB  - The aim of this study was to evaluate the short-term operative results of
      patients with Marfan syndrome who underwent thoracic or abdominal aortic surgery
      in a 4-year period in Japan. Data were collected from the Japan Cardiovascular
      Surgery Database (JCVSD). We retrospectively analyzed the data of 845 patients
      with Marfan syndrome who underwent cardiovascular surgery between January 2008
      and January 2011. Logistic regression was used to generate risk models. The early
      mortality rate was 4.4% (37/845). Odds ratios (OR), 95% confidence intervals
      (CI), and P values for structures and processes in the mortality prediction model
      were as follows: renal insufficiency (OR, 11.37; CI, 3.7234.66; P < 0.001);
      respiratory disorder (OR, 11.12; CI, 3.20-38.67; P < 0.001); aortic dissection
      (OR, 13.02; CI, 2.8060.60; P = 0.001); pseudoaneurysm (OR, 11.23; CI, 1.38-91.66;
      P = 0.024); thoracoabdominal aneurysm (OR, 2.67; CI, 1.22-5.84; P = 0.014); and
      aorticrupure (OR, 4.23; CI, 1.26-14.23; P = 0.002). The mortality prediction
      model had a Cindex of 0.82 and a Hosmer-Lemeshow P value of 0.56. In conclusion,
      this study demonstrated that renal insufficiency and respiratory disorder had
      great impact on the operative mortality of Marfan patients undergoing
      cardiovascular surgery. Because patients with aortic dissection or aortic rupture
      showed high operative mortality, close follow-up to avoid emergency operation is
      mandatory to improve the operative results. Achieving good results from surgery
      of the thoracoabdominal aorta was quite challenging, also in Marfan patients.

PMID- 24309452
TI  - Tocilizumab for the treatment of patients with refractory Takayasu arteritis.
AB  - Treatment of refractory Takayasu arteritis (TA) remains an unresolved clinical
      issue. Patients usually respond to glucocorticoid (GC) therapy, but often relapse
      on tapering of the GC dose. The aim of the present study was to assess the safety
      and efficacy of the interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) in
      patients with TA refractory to conventional therapies including GC. Four patients
      with TA who had shown GC resistance received TCZ infusions (8 mg/kg) every 4
      weeks a total of at least 24 times (range, 24 to 51). Clinical symptoms, the
      serum levels of acute phase proteins and IL-6, GC dosage necessary to maintain
      remission, and cross-sectional imaging by enhanced CT and MRI were assessed. All
      patients achieved good clinical response and rapid normalization of the acute
      phase proteins such as C-reactive protein and serum amyloid A during the therapy
      with TCZ. The mean dosage of prednisolone could be reduced from 21.3 mg/day to
      1.5 mg/day. Although the serum IL-6 level was transiently elevated in all
      patients after several TCZ infusions, it gradually recovered to the initial
      level. Along with the decrease of serum IL-6, two patients exhibited significant
      reduction in thickened arterial lesions. No drug-related adverse effects were
      noted. In this small group of patients with refractory TA, TCZ therapy was
      effective and well-tolerated. Further larger studies should be conducted to
      confirm this finding.

PMID- 24309453
TI  - The periodontal pathogen Aggregatibacter actinomycetemcomitans affects
      experimental autoimmune myocarditis in mice.
AB  - Recent reports assert that dental health is linked to an increased risk of
      cardiovascular disease. It is well known that Aggregatibacter
      actinomycetemcomitans (A.a.) is highly associated with heart disease. Indeed, we
      previously reported that A.a. affects the development of heart disease in a mouse
      model. However, no reports have clarified the relationship between A.a. and
      experimental autoimmune myocarditis (EAM). The aim of this study was to
      investigate the effects of A.a. on EAM in mice. EAM was induced via the injection
      of cardiac myosin into the mice. A.a. or PBS was then injected into the mice
      using a chamber implanted into the back of each mouse. The weight of the organs
      and echocardiograms were obtained and a pathological analysis and quantitative RT
      PCR were performed. Echocardiography showed that no statistical difference was
      observed between the two groups. A histopathological analysis demonstrated that
      the number of areas affected by myocarditis in the A.a.-injected EAM group was
      significantly increased compared to that observed in the PBS-injected EAM group
      (P < 0.05). The hearts of the mice in the A.a.-injected EAM group exhibited
      significantly increased expressions of MMP-9 mRNA compared to the hearts of the
      mice in the PBS-injected EAM group (P < 0.05). These results show that A.a.
      aggravated EAM via an enhanced MMP expression.

PMID- 24309456
TI  - Foreword. The evolution of our health care system.

PMID- 24309454
TI  - Capecitabine induces both cardiomyopathy and multifocal cerebral
      leukoencephalopathy.
AB  - Chemotherapy for malignant tumors has diversified, and recognizing its side
      effects has become more important than ever. Both cardiotoxicity and
      neurotoxicity are rare, but they are among the most serious side effects caused
      by 5-fluorouracil (5-FU). Capecitabine is an orally administered prodrug that
      converts preferentially to 5-FU within tumors, resulting in enhanced
      concentrations of 5-FU in tumor tissue. Given that it targets tumor tissue,
      capecitabine was expected to reduce the risk of side effects associated with
      fluoropyrimidine. Here, we present the case of a 62-year-old man with colorectal
      adenocarcinoma who simultaneously experienced cardiomyopathy with cardiogenic
      shock and cerebral leukoencephalopathy during treatment with capecitabine. During
      emergency coronary angiography, ST-segment elevation and severely reduced left
      ventricular wall motion were observed; however, no severe coronary stenosis or
      spasm was revealed. Furthermore, we present a review of the literature on
      capecitabine-induced cardiotoxicity. As of April 2013, 39 case reports on
      capecitabine-induced cardiotoxicity have been published; however, cardiomyopathy
      was very rare, with only 3 cases reported. It is important for physicians to be
      aware of the various rare, but potentially serious, adverse effects associated
      with capecitabine chemotherapy and to inform patients about the possibility of
      these side effects, including cardiotoxicity and neurotoxicity. 

PMID- 24309457
TI  - Two decades (1993-2012) of adult intensive care unit design: a comparative study
      of the physical design features of the best practice examples.
AB  - In 2006, Critical Care Nursing Quarterly published a study of the physical design
      features of a set of best practice example adult intensive care units (ICUs).
      These adult ICUs were awarded between 1993 and 2003 by the Society of Critical
      Care Medicine (SCCM), the American Association of Critical-Care Nurses, and the
      American Institute of Architects/Academy of Architecture for Health for their
      efforts to promote the critical care unit environment through design. Since 2003,
      several more adult ICUs were awarded by the same organizations for similar
      efforts. This study includes these newer ICUs along with those of the previous
      study to cover a period of 2 decades from 1993 to 2012. Like the 2006 study, this
      study conducts a systematic content analysis of the materials submitted by the
      award-winning adult ICUs. On the basis of the analysis, the study compares the
      1993-2002 and 2003-2012 adult ICUs in relation to construction type, unit
      specialty, unit layout, unit size, patient room size and design, support and
      service area layout, and family space design. The study also compares its
      findings with the 2010 Guidelines for Design and Construction of Health Care
      Facilities of the Facility Guidelines Institute and the 2012 Guidelines for
      Intensive Care Unit Design of the SCCM. The study indicates that the award
      winning ICUs of both decades used several design features that were associated
      with positive outcomes in research studies. The study also indicates that the
      award-winning ICUs of the second decade used more evidence-based design features
      than those of the first decades. In most cases, these ICUs exceeded the
      requirements of the Facility Guidelines Institute Guidelines to meet those of the
      SCCM Guidelines. Yet, the award-winning ICUs of both decades also used several
      features that had very little or no supporting research evidence. Since they all
      were able to create an optimal critical care environment for which they were
      awarded, having knowledge of the physical design of these award-winning ICUs may
      help design better ICUs. 

PMID- 24309458
TI  - Critical thinking: optimal outcomes through end user involvement in the design of
      critical care areas.
AB  - Including end users in evidence-based design is vital to outcomes. The physical
      environment impacts caregiver efficiencies, safety, satisfaction, and quality of
      patient outcomes. End users are more than members of the organization: patients
      should have representation as well. Patients bring value by offering insight from
      a different perspective. Timing is key; therefore, it is critical in obtaining
      desired outcomes, to include end users as early as possible, gaining the most
      insight into the design of the build. Consideration should also be given to best
      practice standards, regulatory compliance, progressive sciences, and
      technologies. Another vital factor is education of the end users on their role
      and expectations for participation in a design team. When end users are educated
      and understand the significance of input, the design team will be able to
      conceive a critical care unit that will meet needs for today and be able to adapt
      to needs for the future. 

PMID- 24309459
TI  - It takes teamwork... the role of nurses in ICU design.
AB  - The changing economic environment in health care is pushing the health care
      construction industry to produce facilities which support improvements in patient
      care, patient experience, patient safety, staff satisfaction, and financial
      outcomes. The successful design, construction, and operation of a new or
      renovated intensive care unit (ICU) requires the participation of intensive care
      nurses to achieve success. A partnership between the architect and nurse,
      definition of the desired operational processes, and knowledge of evidence-based
      design are the foundations of good design. Hospital executives who support the
      participation of nurses in ICU facility projects will gain an efficient and safe
      intensive care facility. 

PMID- 24309460
TI  - Relational sustainability: environments for long-term critical care patients.
AB  - Patients undergoing bone marrow transplant, using spinal cord services, and with
      traumatic brain injury represent a relatively new patient type, requiring both
      intense care and long-term care in the same facility. As medical advances allow
      these patients the opportunity to recover from their critical illnesses or
      injuries, designers and caregivers must give increased attention to the long-term
      critical care environment. Designing for this type of care requires an
      understanding of new technologies and the potential for the built environment to
      address the wide range of physical, sensory, and psychological issues long-term
      inpatients face. Recent work by SmithGroupJJR has provided valuable insights into
      the ways in which lighting, patient room and unit layouts, spatial volumes, and
      other design elements can contribute to the recovery of patients who must spend
      weeks or months in a critical care environment. This knowledge was gained through
      an approach that allows design professionals to immerse themselves in a health
      care institution's values, culture, and work processes. By mapping both
      operational flow and patients' experiences, project teams can develop design
      solutions that sustain the well-being of higher-acuity patients and their family
      members and caregivers. 

PMID- 24309461
TI  - Planning intensive care unit design using computer simulation modeling:
      optimizing integration of clinical, operational, and architectural requirements.
AB  - Nurses have increasingly been regarded as critical members of the planning team
      as architects recognize their knowledge and value. But the nurses' role as
      knowledge experts can be expanded to leading efforts to integrate the clinical,
      operational, and architectural expertise through simulation modeling. Simulation
      modeling allows for the optimal merge of multifactorial data to understand the
      current state of the intensive care unit and predict future states. Nurses can
      champion the simulation modeling process and reap the benefits of a cost
      effective way to test new designs, processes, staffing models, and future
      programming trends prior to implementation. Simulation modeling is an evidence
      based planning approach, a standard, for integrating the sciences with real
      client data, to offer solutions for improving patient care. 

PMID- 24309462
TI  - Patient room considerations in the intensive care unit: caregiver, patient,
      family.
AB  - The Patient Room is one of the most important and costly rooms in the design of
      an inpatient bed unit. As a result, the patient room mock-up requires knowledge
      of the components that inform the patient room environment. This article provides
      the intensive care nurse with questions about patient care processes and unit
      policies that should be considered in a mock-up. The mock-up outcome should align
      with the project's goals and objectives of the health care system, infuse the
      principles of evidence-based design, and ensure that the design accommodates the
      best workflow for the patient population that will be served. The template will
      serve as a guide to evaluate the various features of the patient room and for the
      mock-up discussion between the nurse and the architect. 

PMID- 24309463
TI  - WellStar Paulding Hospital intensive care unit case study: achieving a research
      based, patient-centered design using a collaborative process.
AB  - This article describes the processes and tools used by WellStar Paulding Hospital
      to plan and design a new intensive care unit (ICU) as part of a 108-bed
      replacement hospital on a new site. Seeking to create a culture of safety
      centered around patient care, quality, and efficiency, the team used multiple
      external resources to increase their effectiveness as participants in the design
      process and to ensure that the new ICU achieves the functional performance goals
      identified at the beginning of planning and design. Specific focus on evidence
      based design was assisted through participation in the Center for Health Design's
      Pebble Project process as well as the Joint Commission International Safe Health
      Design Learning Academy Pilot Program. 

PMID- 24309464
TI  - Design for safety in the critical care environment: an evidence-based approach:
      considering the caregiver-patient-family experiences.
AB  - Research supporting the impact of the built environment, while still in its
      infancy, has exerted strong influence on design teams as they seek solutions to
      maximize operational efficiency, address the reduction of errors, and create
      environments that are supportive for patients, families, and staff. This article
      will explore various solutions to addressing the most impactful issues from each
      perspective and will compare solutions against measures of effectiveness. 

PMID- 24309465
TI  - Changes after transformation from a specialized surgical unit to a general mixed
      intensive care unit.
AB  - OBJECTIVES: We report the transition of a specialized surgical intensive care
      unit to a general mixed intensive care unit (ICU) and its influence on immediate
      outcome and performance data of the surgical population before and after the
      reorganization. METHODS: All consecutive patients (2420 admissions) entering the
      surgical intensive care unit, period 2004-2007. After the year 2005, all
      specialized units were combined into 3 general mixed units. RESULTS: Our
      population on the former surgical unit changed from mostly surgical patients to a
      mixed general ICU population, which comprises mostly of cardiac surgery patients.
      We saw better results in all overall outcome domains (ICU mortality, length of
      stay, and percentage of ICU readmissions). The ICU standardized mortality ratio
      remained the same. Surgical patients' outcome did not improve, nor did it
      decrease after the organizational change. CONCLUSION: Organizational changes from
      a surgical ICU to a general mixed unit can have profound influences on
      performance data. Crude ICU outcome improved after the reorganization.
      Nevertheless, ICU standardized mortality ratio did not change.

PMID- 24309466
TI  - Patient outcomes can be associated with organizational changes: a quality
      improvement case study.
AB  - AIMS/BACKGROUND: We report the results of a university surgical intensive care
      (SICU), which are influenced by a reorganization of the department because of a
      downsizing of beds with the corresponding reduction of personnel resulting in a
      decrease in nurse-to-bed ratio. Moreover, we report the subsequent interventions
      and adjustments resulting in favorable results. DESIGN: We performed a
      prospective observational cohort study of all consecutive surgical patients
      entering the SICU of our hospital, over the period 2000-2004. METHODS: In order
      to meet the budget cuts, a reduction of number of SICU beds with a corresponding
      reduction of nursing staff was implemented. In the subsequent period culminating
      on the year 2002, collaboration problems arose between medical and nursing staff:
      resulting in fierce discussions on the floor. Supported through external
      mediators, structures/work ethics/communication/collaborative behavior, and
      organization of the SICU were reviewed and restructured. RESULTS: A total of 1477
      patients were admitted to the SICU. The characteristics, Acute Physiology and
      Chronic Health Evaluation II score and therapeutic intervention scoring system
      points, were not different throughout the years. The intensive care unit-length
      of stay (ICU-LOS) in the admission year 2002 was significantly longer (P = .001)
      and the crude ICU mortality was higher (P = .02) compared with the 2 admission
      years before. The adjusted mortality (ICU standardized mortality ratio) was also
      worse in 2002, however, statistically not different. After the intervention (2003
      and 2004), a better result (crude ICU mortality, length of ICU stay, and ICU
      standardized mortality ratio) was achieved. CONCLUSION: Intensive care
      reorganization, in which higher workload is seen in medical and nursing staff,
      could have a negative effect on ICU outcome and length of ICU stay. RELEVANCE TO
      CLINICAL PRACTICE: Interventions in ICU structures, communication, work ethics,
      and organization have a positive impact in conflict management.

PMID- 24309467
TI  - Reducing Pb poisoning in birds and Pb exposure in game meat consumers: the dual
      benefit of effective Pb shot regulation.
AB  - The use of lead (Pb) ammunition in the form of shot pellets has been identified
      as a Pb exposure risk in wildlife and their human consumers. We explore the
      hypothesis that Pb shot ban enforcement reduces the risk of avian Pb poisoning as
      well as Pb exposure in game meat consumers. We assessed compliance with a partial
      ban on Pb shot commencing in 2003 by examination of 937 waterbirds harvested by
      hunters between 2007 and 2012 in the Ebro delta (Spain). Prevalence of Pb shot
      ingestion was determined, as were Pb concentrations in liver and muscle tissue to
      evaluate the potential for Pb exposure in game meat consumers. Hunted birds with
      only embedded Pb shot (no steel) declined from 26.9% in 2007-08 to <2% over the
      following three hunting seasons after ban reinforcement. Pb shot ingestion in
      mallards decreased from a pre-ban value of 30.2% to 15.5% in the post-ban period.
      Liver Pb levels were predominantly defined by the presence of ingested shot,
      whereas muscle levels were defined by the presence of both ingested and embedded
      shot. Only 2.5% of mallard muscle tissue had Pb levels above European Union
      regulations for meat (0.1MUg/g wet weight) in the 2008-09 season, when Pb shot
      ingestion prevalence was also at a minimum (5.1%). Effective restrictions in Pb
      ammunition use have a dual benefit since this reduces Pb exposure for game meat
      consumers due to embedded ammunition as well as reducing Pb poisoning in
      waterbirds. 

PMID- 24309468
TI  - Phosphorylation of heat shock protein 40 (Hsp40/DnaJB1) by mitogen-activated
      protein kinase-activated protein kinase 5 (MK5/PRAK).
AB  - Heat shock protein 40 (Hsp40) acts as a co-chaperone with Hsp70 to promote
      protein folding, protein transport and degradation. The human Hsp40 family
      contains more than 40 members, some of which can exist as phosphoproteins in the
      cell. However, little is known about the protein kinases responsible for their
      phosphorylation and the functional relevance of this post-translational
      modification remains elusive. Here we show that Hsp40/DnaJB1 is an in vitro and
      in vivo substrate for the mitogen-activated protein kinase-activated protein
      kinase 5 (MK5). MK5 and Hsp40/DnaJB1 form complexes in cells and this interaction
      is accomplished by the C-terminal regions of both proteins. MK5 can phosphorylate
      Hsp40/DnaJB1 at several residues in vitro. Studies with specific
      phosphoantibodies indicate that MK5 phosphorylates Hsp40/DnaJB1 in vivo at Ser
      149 or/and Ser-151 and Ser-171 in the C-terminal domain of Hsp40/DnaJB1. MK5
      modestly stimulates the ATP hydrolyse activity of Hsp40/Hsp70 complex and
      enhances the repression of heat shock factor 1 driven transcription by
      Hsp40/DnaJB1. 

PMID- 24309469
TI  - Downregulation of hepatic stimulator substance during the early phase of liver
      regeneration inhibits E-cadherin expression in mice.
AB  - Hepatic stimulatory substance (HSS), which encodes a sulfhydryl oxidase enzyme,
      promotes liver regeneration (LR) and maintains the viability of hepatocytes.
      Surprisingly, we found that the levels of the HSS mRNA and expressed protein were
      both strongly repressed at 12h after a 70% partial hepatectomy (PH) in mice.
      Understanding the mechanism and effect of this extraordinary suppression can
      provide a novel path for exploring the molecular function of HSS during LR. We
      observed that the EGF levels in the serum were negatively correlated with HSS
      expression in regenerating livers. Treating primary mouse hepatocytes or Hepa1-6
      cells with EGF suppressed HSS mRNA expression. This suppression was
      transcriptional and was mediated by the effect of EGF on the phosphorylation of
      CCAAT/enhancer-binding protein beta (C/EBPbeta), which regulates HSS expression.
      We further showed that the enhanced phosphorylation of C/EBPbeta after PH
      promoted its interaction with the HSS promoter and repressed HSS expression at
      early time-points after PH. Interestingly, the knockdown of HSS caused a dramatic
      decrease in E-cadherin expression in hepatocytes. E-cadherin expression was also
      significantly suppressed at 12h after PH. Moreover, the pre-injection of HSS
      expressing adenovirus vectors prevented E-cadherin suppression after PH.
      Treatment with C/EBPbeta siRNA reversed the EGF-mediated inhibition of HSS
      expression and led to enhanced E-cadherin expression and reduced cell migration.
      Our findings suggest that C/EBPbeta directly inhibits the HSS promoter after PH
      and that this inhibition can downregulate E-cadherin expression. These data
      provide novel insight into the potential role of HSS in hepatic structural
      reconstruction during LR. 

PMID- 24309470
TI  - Erythropoietin production in neuroepithelial and neural crest cells during
      primitive erythropoiesis.
AB  - Erythropoietin (Epo) supports both primitive erythropoiesis in the yolk sac and
      definitive erythropoiesis in the fetal liver and bone marrow. Although definitive
      erythropoiesis requires kidney- and liver-secreted Epo, it is unclear which cells
      produce Epo for primitive erythropoiesis. Here we find neural Epo-producing (NEP)
      cells in mid-gestational stage embryos using mouse lines that express green
      fluorescent protein (GFP) under the Epo gene regulation. In these mice, GFP is
      expressed exclusively in a subpopulation of neural and neural crest cells at
      embryonic day 9.0 when Epo-deficient embryos exhibit abnormalities in primitive
      erythropoiesis. The GFP-positive NEP cells express Epo mRNA and the ex vivo
      culture of embryonic day 8.5 neural tubes results in the secretion of Epo, which
      is able to induce the proliferation and differentiation of yolk sac-derived
      erythroid cells. These results thus suggest that NEP cells secrete Epo and might
      support the development of primitive erythropoiesis. 

PMID- 24309472
TI  - Silicon nanowires: where mechanics and optics meet at the nanoscale.
AB  - Mechanical transducers based on nanowires promise revolutionary advances in
      biological sensing and force microscopy/spectroscopy. A crucial step is the
      development of simple and non-invasive techniques able to detect displacements
      with subpicometer sensitivity per unit bandwidth. Here, we design suspended
      tapered silicon nanowires supporting a range of optical resonances that confine
      and efficiently scatter light in the visible range. Then, we develop an optical
      method for efficiently coupling the evanescent field to the regular interference
      pattern generated by an incoming laser beam and the reflected beam from the
      substrate underneath the nanowire. This optomechanical coupling is here applied
      to measure the displacement of 50 nm wide nanowires with sensitivity on the verge
      of 1 fm/Hz(1/2) at room temperature with a simple laser interferometry set-up.
      This method opens the door to the measurement of the Brownian motion of
      ultrashort nanowires for the detection of single biomolecular recognition events
      in liquids, and single molecule spectroscopy in vacuum. 

PMID- 24309473
TI  - Angioseal VIP(r) vs. StarClose SE(r) closure devices: a comparative analysis in
      non-cardiological procedures.
AB  - BACKGROUND: The aim of this paper was to compare the use of two different
      commercially available vascular closure devices (VCD), Angioseal VIP(r) (St. Jude
      Medical, St. Paul, MN, USA) and StarClose SE (Abbott Laboratories, Abbott Park,
      IL, USA). METHODS: From January 2010 to January 2012, 347 patient underwent
      retrograde femoral arterial puncture for different interventional procedures
      (angioplasty, stenting, embolization for bleeding, fibrinolysis for ischemia and
      chemoembolization). Hemostasis was achieved by deployment of an Angioseal VIP(r)
      (N.=184) or StarClose SE(r) (N.=163). In 94 cases, the retrograde femoral access
      was bilateral and managed with two StarClose SE devices (N.=53) or an Angioseal
      VIP(r) plus a StarClose SE(r) (N.=41). RESULTS: Technical success was obtained in
      95.1% (330/347) of patients. Overall time to hemostasis (TTH) and time to
      ambulation (TTA) were 5,5+/-1,5 min (range 3-8 min) and 6+/-2.5 hr (range 2-9
      hours) respectively. No statistical significative difference (P>0.05) were
      appreciable between to groups for both TTH and TTA: Angioseal VIP(r) TTH was
      5.3+/-1.4 min and StarClose SE(r) TTH was 5.6+/-1.6 min; Angioseal VIP(r) TTA was
      5.9+/-1.8 hr and StarClose SE(r) TTA was 6.1+/-1.9 hr. VAS scores result
      underline a mild difference between two devices. Angioseal VIP(r) patients
      experience a mild to moderate pain within the first 3 minutes from the
      deployment. Whereas StarClose SE(r) patients still experience pain at 5 minutes
      from deployment. The device failure rate was 4.9% (17 cases) and included 13
      minor complications and 4 major complications. Minor complications (3.75%)
      occurred during the initial phase and consisted in recurrent wound bleeding (N.=5
      StarClose SE(r); N.=4 Angioseal VIP(r)) treated with manual compression, and
      hematoma (N.=2 StarClose SE(r); N.=2 Angioseal VIP(r)) that solved spontaneously.
      The 4 major complications (1,15%) were: 1 Angioseal-related common femoral artery
      (CFA) obstruction treated with surgical bypass from the CFA to the superficial
      femoral artery; 1 Angioseal-related CFA dissection solved with surgery; 1
      Angioseal-related embolization of the deep femoral artery partially treated with
      localized fibrinolysis; 1 StarClose-related pseudoaneurysm treated with manual
      compression. CONCLUSIONS: Both Angioseal VIP(r) and StarClose SE(r) systems can
      be considered safe and effective in providing hemostasis following a variety of
      interventional vascular procedures.

PMID- 24309474
TI  - Investing in health: why, what, and three reflections.

PMID- 24309476
TI  - Time for even greater ambition in global health.

PMID- 24309475
TI  - Global health 2035: a world converging within a generation.

PMID- 24309477
TI  - Investing in health: progress but hard choices remain.

PMID- 24309478
TI  - Towards a more robust investment framework for health.

PMID- 24309479
TI  - A grand convergence and a historic opportunity.

PMID- 24309480
TI  - The urgent need for clinical, diagnostic, and operational research for management
      of Buruli ulcer in Africa.
AB  - Despite great advances in the diagnosis and treatment of Buruli ulcer, it is one
      of the least studied major neglected tropical diseases. In Africa, major
      constraints in the management of Buruli ulcer relate to diagnosis and treatment,
      and accessibility, feasibility, and delivery of services. In this Personal View,
      we outline key areas for clinical, diagnostic, and operational research on this
      disease in Africa and propose a research agenda that aims to advance the
      management of Buruli ulcer in Africa. A model of care is needed to increase early
      case detection, to diagnose the disease accurately, to simplify and improve
      treatment, to reduce side-effects of treatment, to deal with populations with HIV
      and tuberculosis appropriately, to decentralise care, and to scale up coverage in
      populations at risk. This approach will require commitment and support to
      strategically implement research by national Buruli ulcer programmes and
      international technical and donor organisations, combined with adaptations in
      programme design and advocacy. A critical next step is to build consensus for a
      research agenda with WHO and relevant groups experienced in Buruli ulcer care or
      related diseases, and we call on on them to help to turn this agenda into
      reality. 

PMID- 24309481
TI  - Brainstem auditory electrophysiology is supressed in term neonates with
      hyperbilirubinemia.
AB  - BACKGROUND: Whether hyperbilirubinemia suppresses electrophysiological activity
      of the neonatal auditory brainstem remains to be investigated. AIM: To determine
      whether hyperbilirubinemia suppresses the brainstem auditory electrophysiology in
      term neonates. METHODS: Maximum length sequence brainstem auditory evoked
      response (MLS BAER) was recorded shortly after confirming hyperbilirubinemia in
      58 term neonates. Wave amplitudes of the response were analyzed in detail.
      RESULTS: Compared with age-matched term controls, the neonates with
      hyperbilirubinemia showed a significant reduction in the amplitudes of MLS BAER
      waves III and particularly V at all click rates 91-910/s. The reduction tended to
      be more significant at higher than lower rates. Wave I amplitude was reduced at
      910/s. V/I amplitude ratio was decreased at all click rates. Therefore, the
      amplitudes of MLS BAER, particularly later, waves were all reduced. The
      amplitudes of all MLS BAER waves tended to be reduced with the increase in total
      serum bilirubin level. All wave amplitudes were correlated with the level of
      total serum bilirubin at some or most click rates. CONCLUSIONS: Brainstem
      auditory electrophysiology is suppressed in neonates with hyperbilirubinemia,
      which related to the severity of hyperbilirubinemia. Wave amplitudes are valuable
      BAER variables to detect functional impairment of the brainstem and auditory
      pathway in neonatal hyperbilirubinemia, and are recommended to be used in
      assessing bilirubin neurotoxicity to the neonatal brain.

PMID- 24309482
TI  - [Pain management in patients with liver cirrhosis].
AB  - Pain management in patients with liver cirrhosis is a real challenge and is often
      inadequate due to a lack of therapeutic efficacy or the high incidence of adverse
      effects. The focus of treatment differs depending on whether the pain is acute or
      chronic and involves understanding the causative pathophysiological mechanism.
      Analgesics should be started with the minimum effective dose and should be
      titrated slowly with avoidance of polypharmacy. Adverse effects must be
      monitored, especially sedation and constipation, which predispose the patient to
      the development of hepatic encephalopathy. The first-line drug is paracetamol,
      which is safe at doses of 2-3g/day. Non-steroidal anti-inflammatory agents are
      contraindicated because they can cause acute renal failure and/or
      gastrointestinal bleeding. Tramadol is a safe option for moderate-severe pain.
      The opioids with the best safety profile are fentanyl and hydromorphone, with
      methadone as an alternative. Topical treatment can reduce oral drug consumption.
      In neuropathic pain the first-line therapeutic option is gabapentin. The use of
      antidepressants such as amitriptyline can be considered in some patients.
      Interventional techniques are a valuable tool in moderate to severe pain, since
      they allow a reduction in drug therapy and consequently its adverse effects.
      Psychological treatment, physical therapy and rehabilitation should be considered
      as part of multimodality therapy in the management of chronic pain. 

PMID- 24309483
TI  - [Corticosteroids and gastroprotection].

PMID- 24309484
TI  - Transfer of antigen from human B cells to dendritic cells.
AB  - The cooperation of B lymphocytes with other antigen presenting cells (APCs) is
      often necessary in the efficient processing and presentation of antigen. Herein,
      we describe a mechanism by which B cells physically interact with dendritic cells
      (DCs) resulting in the transfer of B cell receptor (BCR)-enriched antigen to
      these APCs. Antigen transfer involves direct contact between the two cells
      followed by the capture of B cell derived membrane and intracellular components.
      Strikingly, DCs acquire greater amounts of antigen by transfer from B cells than
      by endocytosis of free antigen. Blocking scavenger receptor A, a DC surface
      receptor involved in membrane acquisition, abrogates these events. We propose
      that antigen transfer from B cells to DCs results in a more focused immunologic
      response due to the selective editing of Ag by the BCR. 

PMID- 24309485
TI  - Left-ventricular hypertrophy and obesity: a systematic review and meta-analysis
      of echocardiographic studies.
AB  - AIM: Left-ventricular hypertrophy (LVH) is a frequent complication in obese
      individuals; an updated review and meta-analysis focusing on this issue is
      lacking. Thus, we analysed the literature in order to provide a comprehensive
      information on the left-ventricular structural changes, as assessed by
      echocardiography, associated to obesity. DESIGN: A literature search using the
      keywords 'left ventricle', 'left-ventricular hypertrophy', 'cardiac hypertrophy',
      'obesity', 'hypertension' and 'echocardiography' was performed in order to
      identify relevant papers. Full articles published in English language in the past
      12 years reporting studies in adult obese individuals were considered. RESULTS: A
      total of 22 studies including 5486 obese individuals were considered. Overall, in
      the pooled obese population, prevalence of LVH, defined by 12 criteria, was 56.0%
      (range 20.0-85.0%). Data provided by 15 studies (n = 4999 obese individuals),
      including 6623 non-obese controls, showed that the probability of having LVH was
      much higher in cases than in non-obese counterparts (odds ratio 4.19, 95%
      confidence interval 2.67-6.53, P < 0.01). A meta-regression analysis (n = 2214;
      14 studies) showed a direct correlation between BMI and left-ventricular mass (P
      < 0.01). Among obese patients with LVH (n = 1930; 15 studies), eccentric
      hypertrophy was more frequent than the concentric phenotype (66 versus 34%; P <
      0.01). CONCLUSIONS: Our analysis shows that LVH is present in a consistent
      fraction of the obese population and that eccentric hypertrophy prevails over the
      concentric phenotype. As obesity-related LVH is a powerful risk factor for
      systolic/diastolic dysfunction, the prevention/treatment of obesity may have a
      strong, favourable impact on incident heart failure.

PMID- 24309486
TI  - Association between serum uric acid, hypertension, vascular stiffness and
      subclinical atherosclerosis: data from the Brisighella Heart Study.
AB  - OBJECTIVE: Serum uric acid (SUA) levels correlate with many recognized
      cardiovascular risk factors, including age, male sex, hypertension, diabetes
      mellitus, hypertriglyceridemia, obesity, and insulin resistance. The aim of our
      study was to verify in a large well characterized population sample the
      relationship between SUA values, hypertension, arterial stiffness and subclinical
      atherosclerosis. METHODS: For this study, we selected 248 men and 371 women adult
      patients enrolled in the last Brisighella Heart Study population survey for which
      a full set of data were available and not consuming antihypertensive,
      antidiabetic, lipid-lowering and uric acid-lowering drugs. SUA and other
      available variables were related to blood pressure level, carotid-femoral pulse
      wave velocity (cfPWV) and carotid intima-media thickness (cIMT). RESULTS:
      Hypertension prevalence was strongly related to SUA quartiles: we found
      significant differences between the 2nd (23.0%) and the 3rd quartiles (36.4%; P
      vs. 2nd < 0.05), and between the 3rd and the 4th quartile (56.3%; P vs. 3rd <
      0.05). Similarly, the metabolic syndrome prevalence increased significantly at
      39.5% in the 3rd SUA quartile (P < 0.05 vs. 2nd) and at 58.9% in the 4th quartile
      (P < 0.05 vs. 3rd). Intima-media thickness gradually and significantly rose along
      quartiles of SUA (P for trend < 0.0001), in particular, it was 0.86  mm in the
      1st quartile, 0.90 in the 2nd, 0.94 in the 3rd, and 0.97 in the last quartile,
      with significant differences between each quartiles (all P < 0.05). In
      multivariate regression analyses, SUA resulted to be significantly associated to
      hypertension and metabolic syndrome prevalence, and IMT. Even if a significant
      association between SUA and cfPWV was found in univariate analysis (P = 0.002),
      when adjusting for age, the trend became nonsignificant (0.20). CONCLUSION: In
      the studied population sample, after adjustment for a large number of parameters,
      SUA appears to be significantly correlated to hypertension and IMT, but not to
      aortic stiffness.

PMID- 24309487
TI  - Relationship between aortic pulse wave velocity, selected proinflammatory
      cytokines, and vascular calcification parameters in peritoneal dialysis patients.
AB  - INTRODUCTION: Vascular calcification and arterial stiffening are cardiovascular
      risk factors among chronic kidney disease patients. Elevated aortic pulse wave
      velocity (AoPWV) is an independent predictor of increased cardiovascular
      morbidity and mortality. OBJECTIVES: The aim of the study was to analyze the
      relationships between inflammatory and vascular calcification parameters and
      arterial wall stiffness in chronic kidney disease (CKD) patients treated by
      peritoneal dialysis. PATIENTS AND METHODS: The study included 57 patients (27
      women and 30 men) aged from 19 to 75 years (mean age 53 +/- 13), treated by
      peritoneal dialysis during 4-100 months (mean 30.4 months). The concentrations of
      albumin, lipids, interleukin-6 (IL-6), IL-18, high-sensitive C-reactive protein,
      transforming growth factor-beta1 (TGF-beta1), osteocalcin, osteoprotegerin (OPG),
      fibroblast growth factor 23, fetuin A, parathyroid hormone (iPTH), total calcium
      (Ca), and phosphates (Pi) were measured. AoPWV was performed using a tonometric
      method, common carotid artery intima-media thickness (CCA-IMT) by ultrasonography
      evaluation, and calcium scoring (CaSc) with multirow spiral computed tomography
      (MSCT). RESULTS: In univariate analysis, AoPWV correlated negatively with
      osteocalcin (R = -0.37; P = 0.005) and positively with OPG (R = 0.41; P = 0.002).
      Additionally, AoPWV was significantly positively associated with inflammatory
      parameters: IL-6 (R = 0.35; P = 0.009), TGF-beta1 (R = 0.27; P = 0.047), and
      white blood cell (WBC) count (R = 0.33; P = 0.01). There were also positive
      correlations between AoPWV and imaging data: CCA-IMT (R = 0.32; P = 0.02) and
      CaSc (R = 0.38; P = 0.004). AoPWV did not correlate with calcium, phosphate, Ca *
      Pi index, or iPTH concentration. After multiple adjustments, osteocalcin was the
      only significant predictor of AoPWV. In logistic regression adjusted for age,
      hypertension, and mean arterial pressure at AoPWV evaluation, only osteocalcin
      was significantly associated with high (above median) AoPWV values [odds ratio
      0.96 (0.92-0.99) per unit increase in osteocalcin]. CONCLUSION: OPG concentration
      and some inflammatory markers (WBC count, IL-6, TGF-beta1) influenced the
      severity of arterial wall stiffness in CKD patients. Measurement of osteocalcin
      seems to be the best predictor of AoPWV.

PMID- 24309488
TI  - Age and the effectiveness of anti-hypertensive therapy on improvement in
      diastolic function.
AB  - OBJECTIVE: Diastolic dysfunction is associated with adverse outcomes and is
      highly prevalent among older adults with hypertension. Lowering SBP with
      antihypertensive therapy has been shown to improve diastolic function, but
      whether or not age influences this effect is unknown. METHODS: In the Exforge
      Intensive Control of Hypertension to Evaluate Efficacy in Diastolic Dysfunction
      trial, 189 patients (age range 45-93 years) with hypertension and diastolic
      dysfunction underwent echocardiography before and after 24 weeks of intensive
      versus standard antihypertensive therapy titrated to a goal SBP below 135 versus
      below 140  mmHg. We performed linear regression analyses to examine the
      association between age and improvement in diastolic function achieved with SBP
      reduction. RESULTS: Antihypertensive therapy reduced SBP by 28 +/- 19  mmHg
      overall, and this was not significantly different across age strata. However,
      percentage improvement in diastolic relaxation velocity (lateral E' peak
      velocity) for every 10  mmHg reduction in SBP was lower in older compared to
      younger patients. In analyses adjusting for age stratum, sex, treatment arm,
      baseline relaxation velocity, and baseline blood pressure, older age was
      associated with reduced improvement in diastolic relaxation velocity per 10  mmHg
      of SBP reduction (beta -1.64, P = 0.009). In contrast, the degree of change in
      left ventricular mass index per 10  mmHg reduction in SBP was not influenced by
      age (P = 0.89). CONCLUSIONS: In our sample of individuals with hypertension and
      diastolic dysfunction, older compared to younger adults experienced less
      improvement in diastolic function in response to similar reductions in SBP.

PMID- 24309489
TI  - Effect of olmesartan medoxomil on number and survival of circulating endothelial
      progenitor cells and calcitonin gene related peptide in hypertensive patients.
AB  - OBJECTIVE: Injury of vascular endothelium, crucial in vascular disease, is
      repaired via circulating endothelial progenitor cells (cEPCs). In hypertension,
      cEPCs number is reduced and function impaired adding further risk for
      cardiovascular (CV) events. Angiotensin II (Ang II)-induced oxidative stress
      (OxSt), accelerates cEPCs senescence. Calcitonin gene-related peptide (CGRP),
      able to prevent and reverse Ang II-induced cEPCs senescence, is reduced in
      hypertension and stimulated by the antioxidant and anti-inflammatory heme
      oxygenase (HO)-1. In essential hypertensive patients olmesartan reduced OxSt and
      markers of CV remodeling and increased HO-1. This study reports in essential
      hypertensive patients the effect of 6 months treatment with olmesartan on plasma
      level of CGRP and number and survival of cEPCs. METHODS AND RESULTS: In 20
      essential hypertensive patients treated with olmesartan medoxomil (20  mg per day
      for 6 months), cEPCs (CD34(+)KDR(+), CD133(+)KDR(+) and CD34(+)CD133(+)KDR(+))
      (direct 3-color flow cytometry analysis), apoptosis of cEPCs (CD133(+)KDR(+)
      cells with Annexin V expression), CGRP determination (ELISA) and HO-1 protein
      level (western blot) were assessed at baseline and after 3 and 6 months of
      treatments. Olmesartan normalized blood pressure (P < 0.001), increased cEPCs
      from baseline (CD34(+)KDR(+): P < 0.003; CD133(+)KDR(+): P < 0.0002;
      CD34(+)CD133(+)KDR(+): P = 0.0008), reduced cEPCs apoptosis (P < 0.001) and
      increased CGRP (P < 0.013) and HO-1 (P = 0.039). CONCLUSION: These results
      provide a mechanistic rationale for the olmesartan's antioxidant and anti
      inflammatory potential translation toward antiatherosclerotic and antiremodeling
      effects reported on clinical ground.

PMID- 24309490
TI  - Superoxide dismutase mimetic, tempol, aggravates renal injury in advanced-stage
      stroke-prone spontaneously hypertensive rats.
AB  - OBJECTIVE: The aim of this study was to determine whether antioxidant therapy
      could relieve hypertension and retard the progression of renal damage in advanced
      stage hypertensive rats. METHODS: Twenty-four-week-old spontaneously hypertensive
      stroke-prone rats were treated for 8 weeks with the superoxide dismutase mimetic
      tempol, low-dose or high-dose candesartan (an angiotensin receptor blocker), or
      hydralazine, and blood pressure and renal damage were compared. RESULTS: Elevated
      blood pressure and renal damage with heterogeneity were present after 8 weeks,
      with greater glomerulosclerosis in the juxtamedullary glomeruli than in the
      superficial glomeruli. Although both tempol and candesartan effectively reduced
      reactive oxygen species production in the kidney, tempol did not decrease blood
      pressure and exacerbated urine protein and histological damage, such as
      glomerulosclerosis and interstitial fibrosis, particularly in juxtamedullary
      nephrons (tempol vs. untreated: glomerulosclerosis index, 2.0 vs. 1.5, P<0.01;
      fibrosis, 15 vs. 10%, P<0.001). In contrast, high-dose candesartan and
      hydralazine prevented these forms of renal damage with lowering blood pressure.
      Low-dose candesartan also prevented this renal damage without lowering blood
      pressure. Moreover, there were increased numbers of larger and smaller glomeruli
      in the juxtamedullary cortex of tempol-treated rats, suggesting that changes in
      glomerular hemodynamics may be responsible for the exacerbation of
      glomerulosclerosis. Both candesartan- and hydralazine-treated rats had glomeruli
      that were slightly decreased in size. CONCLUSION: These results suggest that
      single-antioxidant therapy starting at an advanced-stage may be ineffective for
      hypertension and rather exacerbate renal damage in nonsalt loaded SHRSP.
      Furthermore, lowering blood pressure and inhibiting the renin-angiotensin system
      could be critical for slowing the progression of hypertensive renal damage at an
      advanced stage.

PMID- 24309491
TI  - Rostafuroxin ameliorates endothelial dysfunction and oxidative stress in
      resistance arteries from deoxycorticosterone acetate-salt hypertensive rats: the
      role of Na+K+-ATPase/ cSRC pathway.
AB  - AIMS: Endogenous ouabain is elevated in patients and experimental models of
      hypertension and is associated with elevated mortality. In this context, it is
      reasonable to assume that a new antihypertensive drug that inhibits the
      deleterious effects of endogenous ouabain may be a specific pharmacological tool
      for hypertension treatment. Here, we investigated the effects of rostafuroxin
      (ROSTA), an ouabain inhibitor, on SBP, endothelial dysfunction and oxidative
      stress in deoxycorticosterone acetate (DOCA)-salt rats. METHODS AND RESULTS: A
      hypertensive model was established in uninephrectomized Wistar rats using DOCA
      salt. After SBP stabilization, DOCA-salt rats were divided into two groups: DOCA
      salt (control) and DOCA-salt treatment with ROSTA (1 mg/kg per day gavage, 3
      weeks). The SBP was measured using the tail-cuff method, and vascular function
      was assessed in mesenteric-resistance arteries (MRAs) using a wire myograph.
      Nitric oxide and reactive oxygen species production were investigated. Western
      blot was performed to quantify protein expression. Our results indicated that
      ROSTA treatment decreased SBP, improved acetylcholine-induced relaxation via
      enhanced nitric oxide synthesis and bioavailability, decreased superoxide anion
      generation from NAD(P)H oxidase and cyclooxygenase-2 and reduced cytoplasmic
      tyrosine kinase Src phosphorylation without changes in NaKATPase activity in MRA
      from DOCA-salt rats. CONCLUSION: This study reports the critical role of
      endogenous ouabain in volume-dependent hypertension. In MRA from DOCA-salt rats,
      the binding of endogenous ouabain to NaK-ATPase results in downstream c-SRC
      activation, oxidative stress and endothelial dysfunction. Endogenous ouabain is a
      putative target for the treatment of hypertension, and ROSTA may represent a
      novel therapeutic approach.

PMID- 24309492
TI  - Stabilization of hypoxia inducible factor-1alpha ameliorates acute renal
      neurogenic hypertension.
AB  - OBJECTIVES: Renal neurogenic hypertension (RNH) contributes to cardiovascular
      morbidity. Renal hypoxia may cause RNH and vice versa, leading to a vicious
      circle. Hypoxia adaptation is conferred through hypoxia-inducible factors (HIFs).
      We hypothesized that acute RNH is accompanied by increased renal vascular
      resistance (RVR) and that hypertension and increased RVR are countered by
      increasing HIF-1alpha by cobalt chloride (CoCl2) preconditioning. METHODS: First,
      we studied mean arterial pressure (MAP) and RVR in innervated or denervated
      contralateral kidneys in anesthetized rats before and after unilateral intrarenal
      injection of phenol, a manoeuvre known to elicit acute RNH. Then HIFalpha was
      induced by CoCl2 in drinking water (2 mM, 10 days) after which we compared
      intrarenal isotonic saline or phenol injection on MAP and RVR in CoCl2
      preconditioned and control rats. HIF-1alpha was determined by
      immunohistochemistry. RESULTS: Unilateral intrarenal phenol induced immediate
      rise in MAP and contralateral RVR, and comparable HIF-1alpha upregulation in both
      kidneys, consistent with bi-renal hypoxia. Removing the phenol-injected kidney
      immediately normalized MAP. Contralateral renal denervation had no effect on the
      rise in MAP, but abrogated the contralateral increase in RVR, suggesting
      mediation by increased efferent nerve activity. Strong renal staining for HIF
      1alpha confirmed efficacy of CoCl2 preconditioning, and time-dependent increase
      in heme oxygenase-1 gene expression stabilization of HIFalpha. CoCl2
      preconditioning prior to phenol reduced both DeltaMAP (+10 +/- 2 vs. +20 +/- 3%,
      P=0.015) and DeltaRVR (+21 +/- 11 vs. +90 +/- 26%, P=0.003). CONCLUSION: Acute
      RNH leads to renal vasoconstriction and increased renal HIF-1alpha. Increasing
      HIF-1alpha by CoCl2 preconditioning ameliorates intrarenal phenol-induced RNH and
      renal vasoconstriction.

PMID- 24309494
TI  - Core elements of a TPB paper.

PMID- 24309493
TI  - Combined therapeutic benefit of mitochondria-targeted antioxidant, MitoQ10, and
      angiotensin receptor blocker, losartan, on cardiovascular function.
AB  - OBJECTIVE: Mitochondria-derived reactive oxygen species (ROS) play important
      roles in the development of cardiovascular disease highlighting the need for
      novel targeted therapies. This study assessed the potential therapeutic benefit
      of combining the mitochondria-specific antioxidant, MitoQ10, with the low-dose
      angiotensin receptor blocker (ARB), losartan, on attenuation of hypertension and
      left ventricular hypertrophy. In parallel, we investigated the impact of MitoQ10
      on cardiac hypertrophy in a neonatal cardiomyocyte cell line. METHODS AND
      RESULTS: Eight-week-old male stroke-prone spontaneously hypertensive rats
      (SHRSPs, n=8-11) were treated with low-dose losartan (2.5 mg/kg per day); MitoQ10
      (500 MUmol/l); a combination of MitoQ10 and losartan (M+L); or vehicle for 8
      weeks. Systolic pressure and pulse pressure were significantly lower in M+L rats
      (167.1 +/- 2.9 mmHg; 50.2 +/- 2.05 mmHg) than in untreated SHRSP (206.6 +/- 9
      mmHg, P<0.001; 63.7 +/- 2.7 mmHg, P=0.001) and demonstrated greater improvement
      than MitoQ10 or low-dose losartan alone, as measured by radiotelemetry. Left
      ventricular mass index was significantly reduced from 22.8 +/- 0.74 to 20.1 +/-
      0.61 mg/mm in the combination group (P<0.05). Picrosirius red staining showed
      significantly reduced cardiac fibrosis in M+L rats (0.82 +/- 0.22 A.U.) compared
      with control (5.94 +/- 1.35 A.U., P<0.01). In H9c2 neonatal rat cardiomyocytes,
      MitoQ10 significantly inhibited angiotensin II mediated hypertrophy in a dose
      dependent manner (500  nmol/l MitoQ10 153.7 +/- 3.1 microns vs. angiotensin II
      200.1 +/- 3.6 microns, P<0.001). CONCLUSION: Combining MitoQ10 and low-dose
      losartan provides additive therapeutic benefit, significantly attenuating
      development of hypertension and reducing left ventricular hypertrophy. In
      addition, MitoQ10 mediates a direct antihypertrophic effect on rat cardiomyocytes
      in vitro. MitoQ10 has potential as a novel therapeutic intervention in
      conjunction with current antihypertensive drugs.

PMID- 24309495
TI  - Atomic-scale insight into the formation, mobility and reaction of Ullmann
      coupling intermediates.
AB  - The Ullmann reaction of bromobenzene, the simplest coupling reagent, to form
      biphenyl on a Cu surface proceeds via a highly mobile organometallic intermediate
      in which two phenyl groups extract and bind a single surface Cu atom. 

PMID- 24309497
TI  - NTP-CERHR monograph on Soy Infant Formula.
AB  - Soy infant formula contains soy protein isolates and is fed to infants as a
      supplement to or replacement for human milk or cow milk. Soy protein isolates
      contains estrogenic isoflavones ("phytoestrogens") that occur naturally in some
      legumes, especially soybeans. Phytoestrogens are non-steroidal, estrogenic
      compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and
      these phytoestrogen-sugar complexes are not generally considered hormonally
      active. Phytoestrogens are found in many food products in addition to soy infant
      formula, especially soy-based foods such as tofu, soy milk, and in some over-the
      counter dietary supplements. Soy infant formula was selected for evaluation by
      the National Toxicology Program (NTP) because of the: (1)availability of large
      number of developmental toxicity studies in laboratory animals exposed to the
      isoflavones found in soy infant formula (namely, genistein) or other soy
      products, as well as a number of studies on human infants fed soy infant formula,
      (2)the availability of information on exposures in infants fed soy infant
      formula, and (3)public concern for effects on infant or child development. The
      NTP evaluation was conducted through its Center for the Evaluation of Risks to
      Human Reproduction (CERHR) and completed in September 2010. The results of this
      soy infant formula evaluation are published in an NTP Monograph. This document
      contains the NTP Brief on Soy Infant Formula, which presents NTP's opinion on the
      potential for exposure to soy infant formula to cause adverse developmental
      effects in humans. The NTP Monograph also contains an expert panel report
      prepared to assist the NTP in reaching conclusions on soy infant formula. The NTP
      concluded there is minimal concern for adverse effects on development in infants
      who consume soy infant formula. This level of concern represents a "2" on the
      five-level scale of concern used by the NTP that ranges from negligible concern
      ("1") to serious concern ("5"). This conclusion was based on information about
      soy infant formula provided in the expert panel report, public comments received
      during the course of the evaluation, additional scientific information made
      available since the expert panel meeting in December 2009, and peer reviewer
      critiques of the draft NTP Brief by the NTP Board of Scientific Counselors on May
      10, 2010. 

PMID- 24309496
TI  - Hydroethanolic extract of Pyrostegia venusta (Ker Gawl.) Miers flowers improves
      inflammatory and metabolic dysfunction induced by high-refined carbohydrate diet.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pyrostegia venusta is used in traditional
      Brazilian medicine as a general tonic to treat any inflammatory disease. Several
      studies have demonstrated that medicinal plants constitute a therapeutic approach
      for the treatment of obesity-related metabolic and inflammatory disarrangement.
      Accordingly, we investigated the effects of hydroethanolic extract of Pyrostegia
      venusta flowers (PvHE) supplementation for the treatment of inflammatory and
      metabolic dysfunction induced by high-refined-carbohydrate (HC) diet. MATERIAL
      AND METHODS: The BALB/c mice were fed chow or HC diet for 8 weeks. Part of these
      animals was fed with HC diet supplemented with PvHE on the 9th week until the
      12th week. At the end of the dietary intervention, animals were sacrificed.
      RESULTS: We observed that PvHE decreased adiposity and adipocyte area; improved
      glucose intolerance; reduced serum triacylglycerol levels and systemic
      inflammatory cells; and also reduced some inflammatory mediators levels in
      adipose tissue and liver. CONCLUSION: The results showed that PvHE has beneficial
      effects and may treat inflammatory and metabolic dysfunction induced by HC diet,
      that are associated to a negative modulation of the inflammatory process at
      systemic and local levels.

PMID- 24309498
TI  - Modulation of leukocyte infiltration and phenotype in microporous tissue
      engineering scaffolds via vector induced IL-10 expression.
AB  - Biomaterial scaffolds are central to many tissue engineering strategies as they
      create a space for tissue growth and provide a support for cell adhesion and
      migration. However, biomaterial implantation results in unavoidable injury
      resulting in an inflammatory response, which can impair integration with the host
      and tissue regeneration. Toward the goal of reducing inflammation, we
      investigated the hypothesis that a lentiviral gene therapy-based approach to
      localized and sustained IL-10 expression at a scaffold could modulate the number,
      relative proportions, and cytokine production of infiltrating leukocyte
      populations. Flow cytometry was used to quantify infiltration of six leukocyte
      populations for 21 days following implantation of PLG scaffolds into
      intraperitoneal fat. Leukocytes with innate immune functions (i.e., macrophages,
      dendritic cells, neutrophils) were most prevalent at early time points, while T
      lymphocytes became prevalent by day 14. Reporter gene delivery indicated that
      transgene expression persisted at the scaffold for up to 28 days and macrophages
      were the most common leukocyte transduced, while transduced dendritic cells
      expressed the greatest levels of transgene. IL-10 delivery decreased leukocyte
      infiltration by 50% relative to controls, increased macrophage IL-10 expression,
      and decreased macrophage, dendritic cell, and CD4 T cell IFN-gamma expression.
      Thus, IL-10 gene delivery significantly decreased inflammation following scaffold
      implant into the intraperitoneal fat, in part by modulating cytokine expression
      of infiltrating leukocytes. 

PMID- 24309500
TI  - A method for determining the age of a bloodstain.

PMID- 24309499
TI  - miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a
      regulator of Notch1.
AB  - Dendritic cells (DCs) are critical to initiate the immune response and maintain
      tolerance, depending on different status and subsets. The expression profiles of
      microRNAs (miRNAs) in various DC subsets and haematopoietic stem cells (HSCs),
      which generate DCs, remain to be fully identified. Here we examine miRNomes of
      mouse bone marrow HSCs, immature DCs, mature DCs and IL-10/NO-producing
      regulatory DCs by deep sequencing. We identify numerous stage-specific miRNAs and
      histone modification in HSCs and DCs at different differentiation stages. miR
      30b, significantly upregulated via a TGF-beta/Smad3-mediated epigenetic pathway
      in regulatory DCs, can target Notch1 to promote IL-10 and NO production,
      suggesting that miR-30b is a negative regulator of immune response. We also
      identify miRNomes of in vivo counterparts of mature DCs and regulatory DCs and
      systematically compare them with DCs cultured in vitro. These results provide a
      resource for studying roles of miRNAs in stem cell biology, development and
      functional regulation of DC subsets. 

PMID- 24309502
TI  - Assessment of health-related quality of life of clients in vocational
      rehabilitation: association with depressive symptoms and type of services.
AB  - BACKGROUND: Health-related quality of life (HRQOL) has been frequently used as an
      outcome measure in disability-related studies, yet little is known about HRQOL in
      vocational rehabilitation (VR). AIM: To evaluate HRQOL in VR clients and identify
      factors associated with their HRQOL DESIGN, SETTING AND POPULATION: Cross
      sectional study of 149 clients from 5 VR centers in Switzerland and Germany
      METHODS: HRQOL was measured by 8 dimensions of the Medical Outcomes Study 36-item
      Short Form Health Survey (SF-36) and compared with sex-matched German population
      norms. Multiple regression analyses were conducted to identify whether VR-related
      variables (VR duration and type, sick leave duration) and depressive symptoms
      were associated with HRQOL dimensions independent of sociodemographics (age, sex,
      education) and clinical characteristics (type of disorders, number of
      comorbidities) RESULTS: HRQOL in VR clients was significantly lower in all
      dimensions measured by the SF-36 compared to the general population. Returning to
      the former workplace and being oriented to a new job were associated with less
      functional limitation due to physical problems, less pain and better mental
      health. Being oriented to a new job was also associated with better vitality.
      Presence of depressive symptoms was negatively related with all dimensions of
      HRQOL. Overall, the regression models explained 10%-25% variance of the physical
      HRQOL domain and 18%-27% variance of the mental HRQOL domain. CONCLUSION:
      Multiple dimensions of HRQOL were significantly decreased in VR clients.
      Depressive symptoms were prevalent and contributed significantly to poorer HRQOL,
      thus should be considered in the VR process. Further research is needed to
      ascertain the effect of different VR types to HRQOL and to elaborate the role of
      depressive symptoms in HRQOL over time. CLINICAL REHABILITATION IMPACT:
      Rehabilitation professionals should be informed of the level of HRQOL in VR
      clients in order to tailor effective interventions to improve HRQOL by not only
      focusing on functional ability but also the psychological well-being.

PMID- 24309501
TI  - Test-retest reliability and inter-rater reliability of the Modified Tardieu Scale
      and the Modified Ashworth Scale in hemiplegic patients with stroke.
AB  - BACKGROUND: The most commonly used tools for the assessment of spasticity are the
      Modified Ashworth Scale and Modified Tardieu Scale, but the results on the
      reliability of both scales keep equivocal. AIM: To evaluate the test-retest
      reliability and inter-rater reliability of the Modified Tardieu Scale (MTS) and
      Modified Ashworth Scale (MAS) in hemiplegic patients with stroke. DESIGN: Cross
      sectional study. SETTING: Inpatients referred to a rehabilitation hospital.
      POPULATION: Fifty-one inpatients with hemiplegic stroke. METHODS: MTS and MAS
      were collected from the affected elbow flexors and ankle plantar flexors by: 1)
      two raters who were blinded to the results of the other assessment. 2) one rater
      one day apart. RESULTS: In the MAS measurement, the inter-rater and intra-rater
      Kappa values were 0.66 and 0.69 for the elbow flexors, 0.48 and 0.48 for the
      plantar flexors, respectively. In the angle measurement of the MTS, the inter
      rater and intra-rater ICCs were between 0.58-0.89 for the R1 and R2, and between
      0.62-0.70 for the R1-R2. CONCLUSION: The MAS provided moderate to substantial
      test-retest reliability and inter-rater reliability in the spasticity/tone
      measurement. The agreement of MAS elbow flexors scores was higher than that of
      plantar flexors scores. The reliability of angle measurement in the MTS was
      insufficient. CLINICAL REHABILITATION IMPACT: Further work should avoid observing
      error when taking advantage of angle difference on measuring spasticity.

PMID- 24309503
TI  - Outcomes associated with cardiac rehabilitation participation in patients with
      musculoskeletal comorbidities.
AB  - BACKGROUND: Individuals with coronary artery disease (CAD) and musculoskeletal
      comorbidities (MSKCs) have much to gain from physical activity, yet are less
      likely to be referred to cardiac rehabilitation (CR) than those without MSKCs.
      Whether patients with MSKCs achieve demonstrated benefits of CR participation
      such as improved quantity and quality-of-life remains unknown. AIM: To compare
      all-cause mortality, major acute cardiovascular events (MACEs), quality-of-life
      and psychosocial well-being in patients with CAD and coexisting MSKCs by CR
      participation. DESIGN: Prospective and observational study in which patients were
      administered a questionnaire in the hospital and 1 year later. The cohort was
      linked to provincial databases. SETTING: Eleven hospitals in Ontario, Canada.
      POPULATION: CAD patients (N.=1680). METHODS: CAD inpatients were administered a
      questionnaire assessing sociodemographic and clinical characteristics. Clinical
      data were extracted from charts. CR participation, quality-of-life, depressive
      symptoms, functional status, and physical activity behavior were measured 1 year
      later by questionnaire. The cohort was linked to provincial administrative
      databases to ascertain mortality and MACEs for a median of 2.7 years post-index
      cardiac hospitalization. Associations of CR participation with outcomes were
      tested after adjustment for differences in participation propensity. RESULTS: Of
      study participants, 50.7% (851/1680) had MSKCs and of those with MSKCs, 49.8%
      (424/851) participated in CR. Patients with MSKCs who participated in CR had
      greater physical quality-of-life (P<0.03) and lower mortality than those with
      MSKCs who did not attend CR, after adjusting for propensity for CR participation
      (1.4% vs. 4%; participant vs. non-participants, P=0.03) - non-participants'
      hazard ratio 3.91 [95%CI,1.23-12.36]). There were no differences for MACEs.
      CONCLUSION: Among those with MSKCs, participation in CR is associated with
      survival benefit and better physical quality-of-life compared to non
      participants. CLINICAL REHABILITATION IMPACT: Our findings showing the high
      prevalence of MSKCs in those with CAD and the benefits of CR, add to the
      literature that will provide the basis for exploration of initiatives to improve
      care for those with CAD and MSKC, and to overcome barriers to improved outcomes
      and reduced death. These results will help to guide focused research to optimize
      complex outpatient care in this group, including increasing the utilization of
      CR.

PMID- 24309504
TI  - Fit for purpose? Evaluation of an MSc. in medical physics.
AB  - The National University of Ireland in Galway established a Master in Science
      (MSc.) program in medical physics in 2002. The course was designed to be 90
      ECTS(1) credits and of one calendar year duration. From the outset the MSc. was
      designed to be part of an overall medical physics training program. MSc. programs
      are now widely used as part of the training and education of medical physicists.
      There is however paucity of data on the effectiveness of such courses and the
      purpose of the study reported here is to provide information on one particular
      MSc. course in medical physics. This is relevant to medical physicists who are
      involved in the development and running of medical physics training programs. The
      study used as methodology the Kirkpatrick levels of professional training. It was
      conducted through an online survey, both from students who graduated from the
      course and from students who were in the process of completing the course. The
      survey proved to be an effective way to determine attributes of modules such as
      learning outcomes, knowledge imparted, quality of teaching materials and others.
      The survey proved to be remarkably able to demonstrate interventions in the
      individual course modules. Although the course was shown to be effective in the
      imparting of the knowledge required to become a qualified medical physicist
      several areas for improvement were identified. These are mainly in the areas of
      increased practical experience and in course delivery. 

PMID- 24309505
TI  - Concise and high-yield synthesis of T808 and T808P for radiosynthesis of [(18)F]
      T808, a PET tau tracer for Alzheimer's disease.
AB  - The authentic standard T808 and its corresponding mesylate precursor T808P were
      synthesized in six steps using ethyl vinyl ether and trichlorocetyl chloride as
      starting materials. The overall chemical yields of T808 and T808P were 35% and
      52%, respectively. [(18)F]-T808 was synthesized from T808P by the nucleophilic
      substitution with K[(18)F]F/Kryptofix 2.2.2 and isolated by HPLC combined with
      solid-phase extraction (SPE) purification in 35-45% radiochemical yield with 37
      370GBq/MUmol specific activity at end of bombardment (EOB). 

PMID- 24309506
TI  - A novel double loop control model design for chemical unstable processes.
AB  - In this manuscript, based on Smith predictor control scheme for unstable process
      in industry, an improved double loop control model is proposed for chemical
      unstable processes. Inner loop is to stabilize integrating the unstable process
      and transform the original process to first-order plus pure dead-time dynamic
      stable process. Outer loop is to enhance the performance of set point response.
      Disturbance controller is designed to enhance the performance of disturbance
      response. The improved control system is simple with exact physical meaning. The
      characteristic equation is easy to realize stabilization. Three controllers are
      separately design in the improved scheme. It is easy to design each controller
      and good control performance for the respective closed-loop transfer function
      separately. The robust stability of the proposed control scheme is analyzed.
      Finally, case studies illustrate that the improved method can give better system
      performance than existing design methods. 

PMID- 24309507
TI  - Gene-environment interactions in heavy metal and pesticide carcinogenesis.
AB  - Cancer is a complex disease involving a sequence of gene-environment
      interactions. Lifestyle, genetics, dietary factors, and environmental pollutants
      can increase the risk of cancer. Gene-environment interactions have been studied
      by a candidate-gene approach focusing on metabolism, DNA repair, and apoptosis.
      Here, we review the influence of gene-environment interactions in carcinogenesis,
      with emphasis on heavy metal and pesticide exposures. 

PMID- 24309508
TI  - Development of DNA damage response signaling biomarkers using automated,
      quantitative image analysis.
AB  - The DNA damage response (DDR) coordinates DNA repair with cell cycle checkpoints
      to ameliorate or mitigate the pathological effects of DNA damage. Automated
      quantitative analysis (AQUA) and Tissue Studio are commercial technologies that
      use digitized immunofluorescence microscopy images to quantify antigen expression
      in defined tissue compartments. Because DDR is commonly activated in cancer and
      may reflect genetic instability within the lesion, a method to quantify DDR in
      cancer offers potential diagnostic and/or prognostic value. In this study, both
      AQUA and Tissue Studio algorithms were used to quantify the DDR in radiation
      damaged skin fibroblasts, melanoma cell lines, moles, and primary and metastatic
      melanomas. Digital image analysis results for three markers of DDR (gammaH2AX, P
      ATM, P-Chk2) correlated with immunoblot data for irradiated fibroblasts, whereas
      only gammaH2AX and P-Chk2 correlated with immunoblot data in melanoma cell lines.
      Melanoma cell lines displayed substantial variation in gammaH2AX and P-Chk2
      expression, and P-Chk2 expression was significantly correlated with
      radioresistance. Moles, primary melanomas, and melanoma metastases in brain, lung
      and liver displayed substantial variation in gammaH2AX expression, similar to
      that observed in melanoma cell lines. Automated digital analysis of
      immunofluorescent images stained for DDR biomarkers may be useful for predicting
      tumor response to radiation and chemotherapy. 

PMID- 24309509
TI  - How vascular endothelial growth factor-A (VEGF) regulates differentiation of
      mesenchymal stem cells.
AB  - Vascular endothelial growth factor A (VEGF), a key factor in angiogenesis, plays
      an essential role in skeletal development and postnatal homeostasis. VEGF serves
      as a survival factor for chondrocytes and couples the resorption of cartilage
      with bone formation during endochondral ossification. Recently, it has also been
      found to regulate the balance between osteoblast and adipocyte differentiation in
      bone marrow mesenchymal stem cells. Surprisingly, this regulatory function of
      VEGF is not based on paracrine signaling involving cell surface receptor
      activation. Instead, the mechanism appears to utilize intracellular VEGF, which
      is functionally linked to the nuclear envelope protein lamin A. Lamin A and VEGF
      control osteoblast and adipocyte differentiation by regulating the levels of the
      osteoblast and adipocyte transcription factors Runx2 and PPARgamma, respectively.
      These data raise the intriguing possibility that loss of bone mass during aging
      may be manipulated by controlling the levels and activity of intracellular VEGF
      in bone marrow mesenchymal stem cells. 

PMID- 24309510
TI  - Distribution of corticosteroid receptors in mature oligodendrocytes and
      oligodendrocyte progenitors of the adult mouse brain.
AB  - The expression of glucocorticoid receptors (GRs) was investigated
      immunohistochemically in two different lineages of oligodendrocytes, using
      carbonic anhydrase (CA) II and neuron glial antigen (NG) 2 as markers of mature
      oligodendrocytes and oligodendrocyte progenitors, respectively. We focused on the
      gray matter regions, including CA1, CA3 and the dentate gyrus of the hippocampus,
      the primary somatosensory cortex barrel field and the basolateral amygdala, and
      the white matter regions, including the corpus callosum, external capsule and
      fimbria of the hippocampus. More than 80% of CAII-immunoreactive (IR) cells and
      more than 95% of NG2-IR cells expressed GRs in various regions of the brain. In
      contrast, neither CAII-IR cells nor NG2-IR cells expressed mineralocorticoid
      receptors (MRs) in the same regions. The intensity of GR expression was
      drastically reduced in CA II-IR cells and NG2-IR cells in the same regions in
      adrenalectomized mice. Finally, steroid receptor co-activator (SRC)-1 and p300,
      both of which are cofactors for GR, were expressed in the gray and white matter
      regions in NG2-IR cells, but not in CAII-IR cells. These results suggest that the
      expression of GRs in oligodendrocytes and their progenitor cells mediates several
      functions in vivo, including differentiation and myelination, as a major target
      of glucocorticoids and their cofactors. 

PMID- 24309512
TI  - Multi-kinase inhibition in ovarian cancer.
AB  - Sorafenib (Nexavar) is a multi-kinase inhibitor that was developed as an
      inhibitor of RAF-1, in the ERK1/2 pathway, but which was subsequently shown to
      inhibit class III tyrosine kinase receptors. (1) More recently regorafenib
      (Stivarga) has been developed, which is a further fluorinated version of
      sorafenib with greater bioavailability and similar inhibitory properties against
      RAF-1/class III RTKs. (2) Some of the anti-tumor effects of sorafenib have been
      ascribed to anti-angiogenic actions of this agent on endothelial associated
      kinases such as VEGFR2. Other effects of sorafenib clearly have to be due to its
      effects on the inherent biology of the tumor cells themselves. For example,
      through various mechanisms sorafenib has been shown in the laboratory and the
      clinic to suppress expression of the protective protein MCL-1. (3) Sorafenib has
      also been linked to inhibition of STAT3, NFkappaB, and activation of the death
      receptor CD95. (4) Sorafenib is routinely dosed daily (400 mg BID) and 7 d after
      the start of dosing has a Cmax of ~21 MUM with a nadir at 12 h of ~10 MUM, and is
      a highly protein bound based on in vitro assays. (5) Despite this in vitro
      binding data sorafenib has profound in vivo effects on tumor cells in renal
      carcinoma and hepatocellular carcinoma patients; cells which are not per se
      addicted to high activity oncogene signals that are targets of
      sorafenib/regorafenib. Thus the precise stable bioavailable level of
      sorafenib/regorafenib in patient plasma is not known. 

PMID- 24309513
TI  - Conformational transitions of cinnamoyl CoA reductase 1 from Leucaena
      leucocephala.
AB  - Conformational transitions of cinnamoyl CoA reductase, a key regulatory enzyme in
      lignin biosynthesis, from Leucaena leucocephala (Ll-CCRH1) were studied using
      fluorescence and circular dichroism spectroscopy. The native protein possesses
      four trp residues exposed on the surface and 66% of helical structure, undergoes
      rapid structural transitions at and above 45  degrees C and starts forming
      aggregates at 55  degrees C. Ll-CCRH1 was transformed into acid induced (pH 2.0)
      molten globule like structure, exhibiting altered secondary structure, diminished
      tertiary structure and exposed hydrophobic residues. The molten globule like
      structure was examined for the thermal and chemical stability. The altered
      secondary structure of L1-CCRH1 at pH 2.0 was stable up to 90  degrees C. Also,
      in presence of 0.25 M guanidine hydrochloride (GdnHCl), it got transformed into
      different structure which was stable in the vicinity of 2M GdnHCl (as compared to
      drastic loss of native structure in 2M GdnHCl) as seen in far UV-CD spectra. The
      structural transition of Ll-CCRH1 at pH 2.0 followed another transition after
      readjusting the pH to 8.0, forming a structure with hardly any similarity to that
      of native protein.

PMID- 24309514
TI  - Immobilization of acid phosphatase from Vigna aconitifolia seeds on chitosan
      beads and its characterization.
AB  - Acid phosphatase isolated from Vigna aconitifolia seeds was immobilized onto
      glutaraldehyde activated chitosan beads by crosslinking method. Chitosan beads
      activated with 2% of glutaraldehyde have demonstrated maximum immobilization
      yield (~ 83%). The immobilized enzyme showed optimum activity at pH 7.0, while
      soluble form was maximally active in acidic range (pH 5.0). With respect to free
      form, immobilized acid phosphatase showed better activity in alkaline range. On
      the other side, immobilization does not affect the optimum temperature range
      i.e., both, soluble and immobilized acid phosphatase exhibited maximum activity
      at 60  degrees C. The Km and Vmax values for the immobilized enzyme were
      calculated to be 0.37 mM and 13.5 U/mg. The immobilization on chitosan beads
      enhanced the shelf life of acid phosphatase. The immobilized enzyme retained its
      more than 50% hydrolytic activity for approximately two months. The immobilized
      acid phosphatase was reusable for more than 40 cycles of reaction.

PMID- 24309515
TI  - Commentary to 'Emergency room visits and readmissions after pediatric urologic
      surgery'.

PMID- 24309511
TI  - Protein kinase C, focal adhesions and the regulation of cell migration.
AB  - Cell adhesion to extracellular matrix is a complex process involving protrusive
      activity driven by the actin cytoskeleton, engagement of specific receptors,
      followed by signaling and cytoskeletal organization. Thereafter, contractile and
      endocytic/recycling activities may facilitate migration and adhesion turnover.
      Focal adhesions, or focal contacts, are widespread organelles at the cell-matrix
      interface. They arise as a result of receptor interactions with matrix ligands,
      together with clustering. Recent analysis shows that focal adhesions contain a
      very large number of protein components in their intracellular compartment. Among
      these are tyrosine kinases, which have received a great deal of attention,
      whereas the serine/threonine kinase protein kinase C has received much less. Here
      the status of protein kinase C in focal adhesions and cell migration is reviewed,
      together with discussion of its roles and potential substrates. 

PMID- 24309516
TI  - Tubularized incised plate urethroplasty for the treatment of penile fistulas
      after hypospadias repair.
AB  - OBJECTIVE: Urethrocutaneous fistula is the most common complication of
      hypospadias repair. Tubularized incised plate urethroplasty (TIPU) has been used
      for the management of distal fistulas. This study reports the usage of TIPU in
      the treatment of large penile fistulas. MATERIALS AND METHODS: Between April 2002
      and September 2012, 15 patients with large penile fistulas who were managed with
      TIPU were included in the study. The fistulas were sited along the penile shaft
      from proximal to distal penile localization. Glanular and coronal fistulas were
      excluded. The surgical technique was completed according to the standard TIPU
      technique. The surrounding scar tissue of the fistula was circumferentially
      excised, and the urethral plate at the level of the fistula was incised to
      provide performance of loose urethral tubularization. A urethral stent was kept
      for 5-7 days. RESULTS: The mean age of the patients was 7.3 +/- 3.1 years.
      Primary operation of these patients was tubularized preputial island flap (n =
      6), on-lay preputial island flap (n = 4), and TIPU (n = 5). The sites of the
      hypospadias fistulas were as follows; penoscrotal (three), mid-penile (eight) and
      subcoronal (four). Fistulas recurred in two patients after fistula repair. The
      postoperative follow up of the patients was 12.4 +/- 7.7 months. CONCLUSION: TIPU
      may be used safely for the treatment of fistulas after hypospadias repair.

PMID- 24309517
TI  - Bay-linked perylene bisimides as promising non-fullerene acceptors for organic
      solar cells.
AB  - A series of bay-linked perylene bisimides as non-fullerene acceptors for organic
      solar cells are designed. The best power conversion efficiency up to 3.63% based
      on s-diPBI (1b) is demonstrated by fine-tuning optoelectronic properties
      resulting from different degrees of twisting and flexibility by bay-linkages.

PMID- 24309518
TI  - Entropic depletion of DNA in triangular nanochannels.
AB  - Using Monte Carlo simulations of a touching-bead model of double-stranded DNA, we
      show that DNA extension is enhanced in isosceles triangular nanochannels
      (relative to a circular nanochannel of the same effective size) due to entropic
      depletion in the channel corners. The extent of the enhanced extension depends
      non-monotonically on both the accessible area of the nanochannel and the apex
      angle of the triangle. We also develop a metric to quantify the extent of
      entropic depletion, thereby collapsing the extension data for circular, square,
      and various triangular nanochannels onto a single master curve for channel sizes
      in the transition between the Odijk and de Gennes regimes. 

PMID- 24309520
TI  - [Experience of knowledge translation in the ITSAL (immigration, work and health)
      research project with representatives of the target population].
AB  - This article describes the experience of knowledge translation between
      researchers of the ITSAL (immigration, work and health) project and
      representatives of organizations working with immigrants to discuss the results
      obtained in the project and future research lines. A meeting was held, attended
      by three researchers and 18 representatives from 11 institutions. Following a
      presentation of the methodology and results of the project, the participants
      discussed the results presented and research areas of interest, thus confirming
      matches between the two sides and obtaining proposals of interest for the ITSAL
      project. We understand the process described as an approach to social validation
      of some of the main results of this project. This experience has allowed us to
      open a channel of communication with the target population of the study, in line
      with the necessary two-way interaction between researchers and users. 

PMID- 24309519
TI  - [Healthcare consumption due to musculoskeletal pain in fishery sector workers].
AB  - OBJECTIVE: To determine the frequency and factors associated with medicine
      consumption and consultations with family physicians due to musculoskeletal pain
      in fishery workers. METHODS: We performed a cross-sectional study (n = 929). The
      variables analyzed consisted of sociodemographic factors, the frequency of
      musculoskeletal pain, healthcare resource consumption, back pain disability
      (Roland-Morris) and health-related quality of life (SF-36). RESULTS: A total of
      98.7% of the sample were women, with a mean age of 50.6 years. Musculoskeletal
      pain was reported by 66.5%, 43% were taking medication, and 64% had consulted
      their family physician due to musculoskeletal pain. The factors associated with
      medication intake in the logistic regression analysis were the number of years
      worked in the sector, hip-knee pain, bodily pain and physical functioning. The
      variables associated with physician visits were the presence of hip-knee pain,
      neck-back-shoulder pain, bodily pain, and social functioning. CONCLUSIONS: The
      variables most closely associated with resource utilization were hip-knee pain
      and the physical dimension of health-related quality of life, especially bodily
      pain.

PMID- 24309521
TI  - [Depression in young regular cocaine users recruited in the community].
AB  - OBJECTIVE: To identify the profile of community-recruited regular cocaine users
      and the prevalence of recent depression and associated factors. METHOD: A cross
      sectional study was carried out in 630 regular cocaine users who were not heroin
      consumers. Depression, social support and dependence were evaluated with the
      Composite International Diagnostic Interview, the Duke-Functional Social Support
      Questionnaire, and the Severity of Dependence Scale, respectively. RESULTS: The
      mean age was 23 years and 33% of users were women. The predominant profile of
      cocaine use was recreational-intense. Most (88%) participants had completed
      secondary education. The use of emergency services in the previous year was 45.9%
      and 7.8% were under drug-dependence/psychiatric treatment. The prevalence of
      depression was 14.6%. In the multivariate analysis, the factors associated with
      recent depression were female gender, homelessness, ketamine consumption, and
      less confidential support CONCLUSIONS: Regular cocaine users may require specific
      attention in general health services. Greater access to treatment for depression
      is needed among this group.

PMID- 24309522
TI  - [Assessing the economic impact of adverse events in Spanish hospitals by using
      administrative data].
AB  - OBJECTIVE: To evaluate the incidence and costs of adverse events registered in an
      administrative dataset in Spanish hospitals from 2008 to 2010. METHODS: A
      retrospective study was carried out that estimated the incremental cost per
      episode, depending on the presence of adverse events. Costs were obtained from
      the database of the Spanish Network of Hospital Costs. This database contains
      data from 12 hospitals that have costs per patient records based on activities
      and clinical records. Adverse events were identified through the Patient Safety
      Indicators (validated in the Spanish Health System) created by the Agency for
      Healthcare Research and Quality together with indicators of the EuroDRG European
      project. RESULTS: This study included 245,320 episodes with a total cost of
      1,308,791,871?. Approximately 17,000 patients (6.8%) experienced an adverse
      event, representing 16.2% of the total cost. Adverse events, adjusted by
      diagnosis-related groups, added a mean incremental cost of between ?5,260 and
      ?11,905. Six of the 10 adverse events with the highest incremental cost were
      related to surgical interventions. The total incremental cost of adverse events
      was ? 88,268,906, amounting to an additional 6.7% of total health expenditure.
      CONCLUSIONS: Assessment of the impact of adverse events revealed that these
      episodes represent significant costs that could be reduced by improving the
      quality and safety of the Spanish Health System.

PMID- 24309523
TI  - [Injuries treated in primary care in the Community of Madrid: analyses of
      electronic medical records].
AB  - OBJECTIVE: To describe the incidence of injuries treated in primary care by type
      of injury, age groups, and sex in the publicly-funded health system of the region
      of Madrid in Spain. METHODS: A descriptive cross sectional study was performed of
      injury episodes registered in the primary care electronic medical records of the
      health system of Madrid in 2011. We calculated the global incidence of injuries,
      injury-specific rates for fractures, sprains, wounds, burns, foreign body
      injuries, poisoning and bruises, and their rate ratios with 95% confidence
      intervals, all of which were stratified by sex and age groups. RESULTS: In 2011
      there were 707,800 injury episodes (3.5% of all episodes treated in primary
      care). Most of the injuries occurred in women (54.0%) and in persons older than
      34 years (58.0%). The most common injuries were wounds in men (35.3%) and bruises
      in women (30.6%). Overall, women had higher rates of injuries among the elderly
      and men had more injuries in the group younger than 15 years. By type of injury,
      the highest rates of fractures, burns and bruises were observed in the older
      population, foreign body injuries and wounds in children, sprains in youth, and
      poisonings in extreme ages. CONCLUSIONS: The special vulnerability of boys
      younger than 5 years and elderly women suggests that intervention strategies
      should be targeted to the specific needs of these groups.

PMID- 24309524
TI  - Important milestones in acute leukemia in 2013.
AB  - This year marked the occurrence of several important milestones in the treatment
      of acute leukemias. First, the standard 7 + 3 protocol for acute myeloid leukemia
      (AML) was developed 40 years ago, and with some adaptations, has stood the test
      of time. Second, the 1 millionth hematopoietic cell transplant was recorded this
      year. Stem cell transplant, the first reported by Dr E. Donnall Thomas in 1957,
      had been considered a rare procedure until about a decade ago. Today, it has
      become a proven and often life-saving therapy for patients with acute leukemia.
      Advances in the treatment of patients with AML continue to take place, many of
      which relate to an increased understanding of the clinical heterogeneity of known
      subtypes. Forty years ago, the regimen that has come to be known as 7+3 for acute
      myeloid leukemia (AML) was born [1,2]. Cytosine arabinoside, or
      arabinosylcytosine as it was then called, was given as a continuous intravenous
      infusion of 100 mg/m(2) for 7 days, and the anthracycline, daunorubicin, was
      administered at 45 mg/m(2) intravenously for 3 days. Sixteen patients were
      originally treated on this protocol, and 5 of 8 previously untreated and 2 of 8
      previously treated patients achieved a complete response (CR). This regimen has
      withstood the test of time. Attempts to add or substitute other agents have not
      yielded superior results. The only major contemporary change is that a higher
      dose of daunorubicin is safe and has become the standard of care [3].

PMID- 24309525
TI  - Molecular pathogenesis of AML: translating insights to the clinic.
AB  - Specific combinations of mutations, including FLT3 and IDH1/IDH2/TET2, frequently
      co-occur in acute myeloid leukemia (AML) and are associated with poor prognosis.
      These mutation combinations can be modeled in mice to provide a more genetically
      accurate model of AML. Within these models, stem cells may be different depending
      on how experiments are conducted and based on context. No one mutation can turn
      on a gene; rather the perfect storm of the right genes in the right cell is
      necessary to produce AML. Furthermore, this understanding is therapeutically
      relevant. Rapid and accurate targeted DNA sequencing will identify mutations of
      prognostic and therapeutic significance and will guide treatment choices in the
      future. 

PMID- 24309526
TI  - Osteolineage cells and regulation of the hematopoietic stem cell.
AB  - Over the last 10 years, progress has been made in understanding the relationship
      between hematopoietic stem cells and their microenvironment, or niche. Increased
      knowledge of the microenvironment and its effects on hematopoiesis and
      leukemogenesis based on murine models may lead to the identification of relevant
      new therapeutic targets for leukemia. In particular, the chemokine CCL3 has
      potential as a mediator of leukemia-induced microenvironmental changes, as it has
      been found to be increased in human acute myeloid leukemia. 

PMID- 24309527
TI  - Relapsed acute myeloid leukemia: why is there no standard of care?
AB  - Relapse after achieving a prior response remains one of the most important
      obstacles to improving the outcome of patients with acute myeloid leukemia (AML).
      Although overall, the majority of patients with disease relapse do poorly, this
      is by no means uniform and a number of predictors of outcome have been
      identified. Previously, most trials of investigational agents in the setting of
      disease relapse in AML have accrued a wide range of patients with widely
      different patient and disease characteristics. With increased understanding of
      the biology of the neoplastic change in AML, and better identification of disease
      subsets based on their molecular characterization, target-specific novel agents
      are being developed that will hopefully lead to better strategies, not only for
      treating relapsed disease, but also for the initial induction treatment. 

PMID- 24309528
TI  - Are immunoconjugates approaching "standard of care" in AML?
AB  - It seems clear that immunoconjugates, the combinations of antibodies with toxins,
      will play a role in therapy of acute myeloid leukemia (AML). It is also clear
      that sole emphasis on an average trial result is misplaced in AML, as the example
      of gentuzumab ozogamicin illustrates. Gemtuzumab added to chemotherapy can
      improve survival in many patients with newly diagnosed disease. The future of
      immunoconjugates, however, may rest on further defining the relation between CD33
      and the AML stem cell and its importance in therapy. Three immunoconjugates with
      the cell surface antigens CD33, CD45, and CD30 will be reviewed here. 

PMID- 24309529
TI  - New agents: great expectations not realized.
AB  - A number of new agents in acute myeloid leukemia (AML) have held much promise in
      recent years, but most have failed to change the therapeutic landscape. Indeed,
      with the exception of gemtuzumab ozogamicin (which was subsequently voluntarily
      withdrawn from the commercial market), no new agent has been approved for acute
      myeloid leukemia (AML) beyond the 7 + 3 regimen, which was has been in use for
      over 40 years. This review touches upon the potential reasons for these failures
      and explores the newer therapeutic approaches being pursued in AML.

PMID- 24309530
TI  - The euphoria of hypomethylating agents in MDS and AML: is it justified?
AB  - While it is logical to use hypomethylating agents to treat patients with
      myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), trial results
      with azacitidine and decitabine have been inconsistent. Azacitidine confers a
      survival benefit in higher-risk MDS patients, while decitabine does not. Neither
      agent has demonstrated a survival advantage in older AML patients in prospective
      studies. Reasons for this are explored here along with a recommendation to
      reconsider clinical trial design endpoints. 

PMID- 24309531
TI  - Measurement of minimal residual disease before and after myeloablative
      hematopoietic cell transplantation for acute leukemia.
AB  - Multiparameter flow cytometry (MFC) can identify leukemia-associated
      immunophenotypes in more than 90% of cases of acute leukemia with detection
      limits of 10(-3)-10(-4). In order to better understand the potential utility of
      MFC to measure minimal residual disease (MRD) in the setting of myeloablative
      hematopoietic cell transplantation (HCT), we studied cohorts of patients with
      acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in complete
      remission (CR) both pre- and post-HCT. Among 253 patients with AML, the 3-year
      estimates of overall survival were 73% (CR1) and 73% (CR2) for those who were
      MRD(neg) and 32% (CR1) and 44% (CR2) for those who were MRD(pos), with relapse
      rates being more than doubled in those who were MRD(pos) pre-HCT (21% vs 58% for
      CR1 patients and 19% vs 68% for CR2 patients). The presence of MRD anytime during
      the first 100 days post-HCT predicted a 6-fold higher risk of subsequent relapse.
      In 157 patients with ALL, the 3-year overall survivals were 68% for the MRD(neg)
      cohort vs 40% for those who were MRD(pos) pre-HCT, with probabilities of relapse
      of 16% in those who were MRD(neg) vs 33% in the MRD(pos) group. As in AML, the
      presence of MRD in the post-transplant setting indicated that the risk of
      subsequent relapse was high, but not inevitable. 

PMID- 24309533
TI  - Which donor or graft source should you choose for the strongest GVL? Is there
      really any difference.
AB  - Patients undergoing allogeneic hematopoietic cell transplantation (HCT) face
      relapse of their malignancy as the most frequent cause of treatment failure. It
      has been postulated that the allogeneic neoplastic potency of different donor or
      graft sources may differ and in some situations, a particular graft source might
      be preferred. Data on this supposition has been reviewed here to consider HLA
      matched siblings, HLA-matched or partially matched unrelated donors (URD),
      unrelated umbilical cord blood (UCB), and haploidentical as well as blood or
      marrow grafts. 

PMID- 24309534
TI  - Reduced intensity allogeneic hematopoietic transplantation is an established
      standard of care for treatment of older patients with acute myeloid leukemia.
AB  - Allogeneic hematopoietic transplantation, an effective treatment for acute
      myeloid leukemia (AML), was originally developed as a means of delivering high
      dose myeloablative chemotherapy or radiation. The transplant itself allowed stem
      cells to restore normal hematopoiesis and immunity. Yet older people were denied
      this treatment because the myeloablative therapy has considerable toxicity. More
      recently, reduced-intensity conditioning has been used, allowing older or
      medically infirm patients to receive a transplant. This review explores the
      feasibility of transplant as a standard of care for older patients. 

PMID- 24309532
TI  - Acute graft-versus-host disease: are we close to bringing the bench to the
      bedside?
AB  - Graft-versus-host disease (GVHD) is a major complication of allogeneic
      hematopoietic stem cell transplant (AHSCT) associated with significant morbidity
      and mortality. This review focuses on the pathophysiology, prevention, and
      treatment of acute GVHD. Specifically, we explain how new discoveries in
      immunology have expanded our understanding of GVHD, in which tissue damage from
      chemotherapy or radiation results in cytokine release, activating T cells,
      resulting in proliferation and differentiation, trafficking to target organs, and
      tissue destruction and inflammation. Insights into the mechanisms of this disease
      relate directly to the development of preventive strategies and therapies, such
      as immunosuppression, calcineurin inhibitors, T-cell depletion, CCR5 antagonists,
      gut decontamination, extracorporeal photopheresis, and more. Understanding the
      immunobiology of GVHD and developing effective preventions and treatments are
      critical to the continuing success of AHSCT. 

PMID- 24309535
TI  - Rational approach to pulmonary infiltrates in leukemia and transplantation.
AB  - At present, a number of invasive diagnostic techniques can be used to diagnose
      the cause of lung infiltrates in patients with hematologic malignancies or
      hematopoietic stem cell transplantation recipients. Bronchoscopy with measurement
      of biomarkers in the bronchoalveolar lavage (BAL) will most likely become the
      preferred method to diagnose infectious causes of pulmonary infiltrates. However,
      there is no uniform approach regarding the technical parameters of the lavage
      procedure in cancer patients. Diagnostic protocols vary by region, center, and
      the expertise of the staff. This mini review discusses the issues surrounding
      diffuse pulmonary infiltrates and provides some recommendations to deal with
      these issues. 

PMID- 24309537
TI  - Influence of partial volume correction in staging of head and neck squamous cell
      carcinoma using PET/CT.
AB  - Aim: PET/CT is widely used for the detection of lymph node involvement in head
      and neck squamous cell carcinoma (HNSCC). However, PET qualitative and
      quantitative capabilities are hindered by partial volume effects (PVE).
      Therefore, a retrospective study on 32 patients (57 lymph nodes) was carried out
      to evaluate the potential improvement of PVE correction (PVEC) in FDG PET/CT
      imaging for the diagnosis of HNSCC. Histopathological analysis of lymph nodes
      following neck dissection was used as the gold standard. Methods: A previously
      proposed deconvolution based PVEC approach was used to derive improved
      quantitative accuracy PET images, while the anatomical lymph node volumes were
      determined on the CT images. Different parameters including SUVmax and SUVmean
      were derived from both original and PVEC PET images for each patient. Results:
      Histopathology confirmed that SUVmax and SUVmean after PVEC allows a
      statistically significant differentiation of malignant and benign lymph nodes
      (p<0.05). The sensitivity of SUVmax and SUVmean was 64% and 57% respectively with
      or without PVEC. PVEC increased specificity from 71% to 76% for SUVmax and 57% to
      66% for SUVmean. Corresponding accuracy increased from 66% to 71% for SUVmax and
      from 59% to 66% for SUVmean. However, the most accurate differentiation between
      benign and malignant nodes was obtained while using the magnitude of SUVmax
      increase after PVEC with a corresponding sensitivity, specificity and accuracy of
      77%, 82% and 80% respectively. Conclusion: Our work shows that the use of partial
      volume effects correction allows a more accurate nodal staging using FDG PET
      imaging in HNSCC.

PMID- 24309536
TI  - Phosphorylase re-expression, increase in the force of contraction and decreased
      fatigue following notexin-induced muscle damage and regeneration in the ovine
      model of McArdle disease.
AB  - McArdle disease is caused by a deficiency of myophosphorylase and currently a
      satisfactory treatment is not available. The injection of notexin into, or the
      layering of notexin onto, the muscles of affected sheep resulted in necrosis
      followed by regeneration of muscle fibres with the expression of both non-muscle
      isoforms of phosphorylase within the fibres and a reduction of the amount of
      glycogen in the muscle with an increase in the strength of contraction and a
      decrease in fatiguability in the muscle fibres. The sustained re-expression of
      both the brain and liver isoforms of phosphorylase within the muscle fibres
      provides further emphasis that strategies to enhance the re-expression of these
      isoforms should be investigated as a possible treatment for McArdle disease. 

PMID- 24309538
TI  - Biocompatible and flexible graphene oxide/upconversion nanoparticle hybrid film
      for optical pH sensing.
AB  - Free-standing optical hybrid film which is composed of positively-charged
      polyethylenimine-coated NaYF4:Yb,Er nanoparticles and negatively-charged graphene
      oxide (GO) has been developed to measure pH based on the pH-dependent
      luminescence quenching effect caused by GO. The isothermal titration calorimetry
      analyses indicate that the interaction between GO and NaYF4:Yb,Er nanoparticles
      becomes stronger with increasing pH, leading to a more significant fluorescence
      quenching of NaYF4:Yb,Er nanoparticles at high pH values. The excellent
      mechanical properties of the hybrid film endow the thin-film pH sensor with
      better repeatability and higher stability during the measurements.
      Quantitatively, the upconversion luminescence intensity of the hybrid film
      exhibits a linear trend over the pH range of 5.00-8.00. Because of excitation
      with a 980 nm laser, as expected, the hybrid film sensor is also sensitive to the
      urine measurements with reduced background absorption. In addition to its good
      biocompatibility, our free-standing hybrid film sensor would be a promising
      candidate for biological, medical, and pharmaceutical applications. 

PMID- 24309539
TI  - Rapid interhemispheric climate links via the Australasian monsoon during the last
      deglaciation.
AB  - Recent studies have proposed that millennial-scale reorganization of the ocean
      atmosphere circulation drives increased upwelling in the Southern Ocean, leading
      to rising atmospheric carbon dioxide levels and ice age terminations. Southward
      migration of the global monsoon is thought to link the hemispheres during
      deglaciation, but vital evidence from the southern sector of the vast
      Australasian monsoon system is yet to emerge. Here we present a 230thorium-dated
      stalagmite oxygen isotope record of millennial-scale changes in Australian
      Indonesian monsoon rainfall over the last 31,000 years. The record shows that
      abrupt southward shifts of the Australian-Indonesian monsoon were synchronous
      with North Atlantic cold intervals 17,600-11,500 years ago. The most prominent
      southward shift occurred in lock-step with Heinrich Stadial 1 (17,600-14,600
      years ago), and rising atmospheric carbon dioxide. Our findings show that
      millennial-scale climate change was transmitted rapidly across Australasia and
      lend support to the idea that the 3,000-year-long Heinrich 1 interval could have
      been critical in driving the last deglaciation.

PMID- 24309540
TI  - Emerging technologies advancing forage and turf grass genomics.
AB  - Grassland is of major importance for agricultural production and provides
      valuable ecosystem services. Its impact is likely to rise in changing socio
      economic and climatic environments. High yielding forage grass species are major
      components of sustainable grassland production. Understanding the genome
      structure and function of grassland species provides opportunities to accelerate
      crop improvement and thus to mitigate the future challenges of increased feed and
      food demand, scarcity of natural resources such as water and nutrients, and high
      product qualities. In this review, we will discuss a selection of technological
      developments that served as main drivers to generate new insights into the
      structure and function of nuclear genomes. Many of these technologies were
      originally developed in human or animal science and are now increasingly applied
      in plant genomics. Our main goal is to highlight the benefits of using these
      technologies for forage and turf grass genome research, to discuss their
      potentials and limitations as well as their relevance for future applications. 

PMID- 24309541
TI  - pH-sensitive nano-systems for drug delivery in cancer therapy.
AB  - Nanotechnology has been widely used in the development of new strategies for drug
      delivery and cancer therapy. Compared to traditional drug delivery systems, nano
      based drug delivery system have greater potential in a variety of areas, such as
      multiple targeting functionalization, in vivo imaging, combined drug delivery,
      extended circulation time, and systemic control release. Nano-systems
      incorporating stimulus-responsive materials have remarkable properties which
      allow them to bypass biological barriers and achieve targeted intracellular drug
      delivery. As a result of the active metabolism of tumor cells, the tumor
      microenvironment (TME) is highly acidic compared to normal tissues. pH-Sensitive
      nano-systems have now been developed in which drug release is specifically
      triggered by the acidic tumor environment. Studies have demonstrated that novel
      pH-sensitive drug delivery systems are capable of improving the efficiency of
      cancer treatment. A number of these have been translated from bench to clinical
      application and have been approved by the Food and Drug Administration (FDA) for
      treatment of various cancerous diseases. Herein, this review mainly focuses on pH
      sensitive nano-systems, including advances in drug delivery, mechanisms of drug
      release, and possible improvements in drug absorption, with the emphasis on
      recent research in this field. With deeper understanding of the difference
      between normal and tumor tissues, it might be possible to design ever more
      promising pH-responsive nano-systems for drug delivery and cancer therapy in the
      near future. 

PMID- 24309542
TI  - USP3 controls BRCA1 "foci".

PMID- 24309543
TI  - Another face of cell death.

PMID- 24309544
TI  - p73 keeps metabolic control in balance.

PMID- 24309545
TI  - [Myopericarditis as the presenting manifestation of adult Still's disease].
AB  - INTRODUCTION: Adult Still's disease may present with multiple non-specific
      clinical manifestations leading to diagnostic difficulties. Presentation as
      initial myopericarditis is rare but must be known. CASE REPORT: We report a 49
      year-old man who presented with the sudden onset of a high fever, arthralgia and
      myalgia, skin rash, dyspnea and chest pain related to a myopericarditis.
      Infectious, neoplastic and autoimmune diagnostic work-up was non-contributive.
      Adult Still's disease was discussed and confirmed by the decrease in the
      glycosylated fraction of ferritin. Corticosteroids followed by interleukin-1
      receptor antagonist (anakinra) therapy allowed a rapid improvement in clinical
      and biological manifestations. CONCLUSION: Adult Still's disease should be
      considered in any systemic inflammatory disease without a diagnosis, even with
      atypical manifestations, especially since it can be life-threatening in the
      absence of treatment.

PMID- 24309546
TI  - [Therapeutic update in cystic fibrosis].
AB  - We present the recent therapeutic advances in the cystic fibrosis care. It
      concerns improvements in symptomatic treatment with the development of dry powder
      inhaled antibiotics that improved quality of life, and innovative treatments
      namely the modulators of the cystic fibrosis transmembrane protein conductance
      regulator (CFTR), molecules which act specifically at the level of the defective
      mechanisms implied in the disease. The life expectancy of cystic fibrosis
      patients born after 2000, is estimated now to be about 50 years. This improvement
      of survival was obtained with the organization of the care within the specialized
      centers for cystic fibrosis (Centre de ressource et de competences de la
      mucoviscidose) and remains still based on heavy symptomatic treatments. Dry
      powder inhaled antibiotics constitute a significant time saving for patients to
      whom all the care can achieve two hours daily. Since 2012, the modulators of
      CFTR, molecules allowing a pharmacological approach targeted according to the
      type of the mutations, allows a more specific approach of the disease. Ivacaftor
      (Kalydeco((r))) which potentialises the function of the CFTR protein expressed on
      the cellular surface is now available for patients with the G551D mutation.
      Lumacaftor is going to be tested in association with ivacaftor in patients with
      the F508del mutation, that is present in at least 75% of the patients. The
      ataluren which allows the production of a functional protein CFTR in patients
      with a no sense mutation is the third representing of this new therapeutic class.
      We presently have numerous symptomatic treatments for the cystic fibrosis care.
      The development of CFTR modulators, today available to a restricted number of
      patients treated with ivacaftor represents a very promising therapeutic avenue.
      It will represent probably the first step to a personalized treatment according
      to CFTR genotype.

PMID- 24309547
TI  - [Warfarin-related nephropathy: a case report].
AB  - INTRODUCTION: Warfarin-related nephropathy (WRN) is a newly recognized entity,
      which is characterized by the occlusion of renal tubules by red blood cells
      following glomerular hemorrhage in a patient overexposed to warfarin
      (international normalized ratio>3). CASE REPORT: We report a 70-year-old man with
      no previous renal condition who developed WRN when his INR was>12. He did not
      fully recover his previous renal function. CONCLUSION: The diagnosis of WRN
      should be considered whenever INR exceeds 3 in patients exposed to warfarin,
      particularly in the presence of hematuria. Vitamin K is the only therapeutic
      option.

PMID- 24309548
TI  - Reprint of "fish immunity to scuticociliate parasites".
AB  - Some species of scuticociliates (Ciliophora) behave as facultative parasites and
      produce severe mortalities in cultured fish. Pathogenic scuticociliates can cause
      surface lesions and can also penetrate inside the body, where they feed on tissue
      and proliferate in the blood and most internal organs, killing the host in a few
      days. In this review, we describe the current knowledge on the protective role of
      fish cellular and humoral immune responses against these parasites. Immune
      humoral factors, especially complement, are of particular importance in defending
      fish against these ciliates. However, knowledge about how the fish immune system
      responds to scuticociliates is scant, and the cellular and molecular events that
      occur during the response are not known. We also describe the possible mechanisms
      used by scuticociliates to avoid or resist the defensive reaction of the host.
      For example, the release of proteases can help parasites enter fish tissues and
      impair the fish cellular and humoral responses. Several vaccine formulations
      containing scuticociliates have induced a good antibody response and protection
      in fish immunized and challenged with homologous strains of particular species.
      However, protection was not achieved in fish immunized and challenged with
      heterologous strains, and the antigens involved in protection and the antigenic
      differences between heterologous strains have not yet been determined. 

PMID- 24309549
TI  - Ionic partitioning and stomatal regulation: dissecting functional elements of the
      genotypic basis of salt stress adaptation in grafted melon.
AB  - Vegetable grafting is commonly claimed to improve crop's tolerance to biotic and
      abiotic stresses, including salinity. Although the use of inter-specific
      graftings is relatively common, whether the improved salt tolerance should be
      attributed to the genotypic background rather than the grafting per se is a
      matter of discussion among scientists. It is clear that most of published
      research has to date overlooked the issue, with the mutual presence of self
      grafted and non-grafted controls resulting to be quite rare within experimental
      evidences. It was recently demonstrated that the genotype of the rootstock and
      grafting per se are responsible respectively for the differential ion
      accumulation and partitioning as well as to the stomatal adaptation to the
      stress. The present paper contributes to the ongoing discussion with further data
      on the differences associated to salinity response in a range of grafted melon
      combinations. 

PMID- 24309550
TI  - Factors affecting surgical results of Wassel type IV thumb duplications.
AB  - The aim of this study is to review the outcomes of Wassel type IV thumb
      duplications with a minimum of one year follow-up, and to identify any factors
      that may compromise the quality of results. Forty one patients (42 thumbs)
      returned for assessment of thumb alignment, metacarpophalangeal joint and
      interphalangeal joint stability and motion; carpometacarpal joint motion; pinch
      and grip strengths; and thumb size. The subjective assessment considered thumb
      shape and contour, scarring, nail deformity and examiner and patient/parent
      satisfaction. The mean age at surgery was 16 months and the mean follow-up time
      was 79 months. Metacarpophalangeal joint and interphalangeal joint mal-alignment
      was present in 56% and 38% of cases, respectively. Interphalangeal ulnar
      collateral ligament laxity was significant. Metacarpophalangeal joint and
      interphalangeal joint motion was significantly decreased. Pinch and grip strength
      measurements were normal. A novel and comprehensive assessment scale is
      introduced, which revealed results of one (2.5%) excellent, 23 (59%) good, 14
      (36%) fair and one (2.5%) poor. We consider that greater attention should be
      directed to the avoidance of mal-alignment and instability to improve these
      results. 

PMID- 24309551
TI  - Modeling the relaxation time of DNA confined in a nanochannel.
AB  - Using a mapping between a Rouse dumbbell model and fine-grained Monte Carlo
      simulations, we have computed the relaxation time of lambda-DNA in a high ionic
      strength buffer confined in a nanochannel. The relaxation time thus obtained
      agrees quantitatively with experimental data [Reisner et al., Phys. Rev. Lett.
      94, 196101 (2005)] using only a single O(1) fitting parameter to account for the
      uncertainty in model parameters. In addition to validating our mapping, this
      agreement supports our previous estimates of the friction coefficient of DNA
      confined in a nanochannel [Tree et al., Phys. Rev. Lett. 108, 228105 (2012)],
      which have been difficult to validate due to the lack of direct experimental
      data. Furthermore, the model calculation shows that as the channel size passes
      below approximately 100 nm (or roughly the Kuhn length of DNA) there is a
      dramatic drop in the relaxation time. Inasmuch as the chain friction rises with
      decreasing channel size, the reduction in the relaxation time can be solely
      attributed to the sharp decline in the fluctuations of the chain extension.
      Practically, the low variance in the observed DNA extension in such small
      channels has important implications for genome mapping. 

PMID- 24309552
TI  - Abortion care for adolescent and young women.
AB  - BACKGROUND: Unintended pregnancy among adolescents (10-19years) and young women
      (20-24years) is a global public health problem. Adolescents face challenges in
      accessing safe abortion care. OBJECTIVE: To determine, via a systematic data
      review, whether abortion care for adolescent and young women differs clinically
      from that for older women. METHODS: In a comprehensive data review, the Cochrane
      Central Register of Controlled Trials, MEDLINE, and POPLINE databases were
      searched from the earliest data entered until November 2012. Randomized
      controlled trials and observational studies comparing effectiveness, safety,
      acceptability, and long-term sequelae of abortion care between adolescent/young
      women and older women were identified. Two reviewers independently extracted
      data, and the Cochrane guidelines and Newcastle-Ottawa Scale were used for
      quality assessment. RESULTS: In total, there were 25 studies including 346 000
      women undergoing first- and second-trimester medical abortion, vacuum aspiration,
      or dilation and evacuation. Effectiveness and overall complications were similar
      among age groups. However, younger women had an increased risk for cervical
      laceration and a decreased risk of uterine perforation and mortality.
      Satisfaction and long-term depression were similar between age groups. Except for
      less uptake of intrauterine devices among adolescents, age did not affect post
      abortion contraception. CONCLUSIONS: Evidence from various healthcare systems
      indicates that abortion is safe and efficacious among adolescent and young women.
      Clinical services should promote access to safe abortion for adolescents.

PMID- 24309553
TI  - Highly specific enrichment of N-linked glycopeptides based on hydrazide
      functionalized soluble nanopolymers.
AB  - In this work, for the first time, hydrazide functionalized PAMAM was designed and
      synthesized for efficient and selective enrichment of N-linked glycopeptides from
      complex biological samples using FASP (filter-aided sample preparation) mode. 

PMID- 24309554
TI  - Acetazolamide in retinoschisis: a prospective study.

PMID- 24309555
TI  - Morphological and molecular differentiation of Parastrigea (Trematoda:
      Strigeidae) from Mexico, with the description of a new species.
AB  - Parastrigea plataleae n. sp. (Digenea: Strigeidae) is described from the
      intestine of the roseate spoonbill Platalea ajaja (Threskiornithidae) from four
      localities on the Pacific coast of Mexico. The new species is mainly
      distinguished from the other 18 described species of Parastrigea based on the
      ratio of its hindbody length to forebody length. A principal component analysis
      (PCA) of 16 morphometric traits for 15 specimens of P. plataleae n. sp., five of
      Parastrigea cincta and 11 of Parastrigea diovadena previously recorded in Mexico,
      clearly shows three clusters, which correspond to the three species. DNA
      sequences of the internal transcribed spacers (ITSs) of ribosomal DNA and the
      mitochondrial gene cytochrome c oxidase subunit I (cox 1) were used to
      corroborate this morphological distinction. The genetic divergence estimated
      among P. plataleae n. sp., P. cincta and P. diovadena ranged from 0.5 to 1.48%
      for ITSs and from 9.31 to 11.47% for cox 1. Maximum parsimony (MP) and maximum
      likelihood (ML) analyses were performed on the combined datasets (ITSs+cox 1) and
      on each dataset alone. All of the phylogenetic analyses indicated that the
      specimens from the roseate spoonbill represent a clade with strong bootstrap
      support. The morphological evidence and the genetic divergence in combination
      with the reciprocal monophyly in all of the phylogenetic trees support the
      hypothesis that the digeneans found in the intestines of roseate spoonbills
      represent a new species. 

PMID- 24309556
TI  - Simultaneous microdetermination of bosentan, ambrisentan, sildenafil, and
      tadalafil in plasma using liquid chromatography/tandem mass spectrometry for
      pediatric patients with pulmonary arterial hypertension.
AB  - A simultaneous, selective, sensitive, and rapid liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) method was developed and validated for the quantification
      of bosentan, ambrisentan, sildenafil, and tadalafil in 50MUL of human blood
      plasma. Diluted plasma samples were extracted using a solid-phase extraction
      procedure with 2% formic acid and methanol. The four drugs were separated by high
      performance liquid chromatography using a C18 column and an isocratic mobile
      phase running at a flow rate of 0.2mL/min for 5min. The drugs were detected by a
      tandem mass spectrometer with electrospray ionization using deuterated compounds
      as internal standards. Calibration curves were generated over the linear
      concentration range of 2-1000ng/mL in plasma with a lower limit of quantification
      of 2ng/mL for all compounds. Finally, this validated method was applied to a
      clinical pharmacokinetic study in pediatric patients with pulmonary arterial
      hypertension (PAH) following the oral administration of PAH drugs. These results
      indicate that this method is suitable for assessing the risk/benefit of
      combination therapy in the pediatric population and useful for therapeutic drug
      monitoring for PAH treatment. 

PMID- 24309557
TI  - Ultra high performance liquid chromatography coupled with high resolution
      quantitation mass spectrometry method development and validation for determining
      genotoxic 2,5-dichlorobenzoyl chloride in MLN9708 drug substance.
AB  - A novel reversed-phase ultra high performance liquid chromatography coupled with
      high resolution quantitation mass spectrometry (UHPLC/HRQMS) method was developed
      to quantify 2,5-dichlorobenzoyl chloride (DCBC), a genotoxic impurity, in MLN9708
      drug substance. A surrogate strategy was utilized whereby DCBC was intentionally
      hydrolyzed to 2,5-dichlorobenzoic acid (DCBA) to provide a stable and reliable
      detection target. The hydrolysis approach was conservative since the measured
      signal represented the sum of DCBC and DCBA in MLN9708 drug substance, and such
      approach was acknowledged and accepted by food and drug administration (FDA).
      HRQMS was used as the detection method since conventional MS/MS methodology gave
      poor sensitivity and selectivity due to non-specific fragmentation of carbon
      dioxide loss upon collision activation dissociation. Profile algorithm mass
      spectrometry data were acquired with mass resolving power (MRP) of 60,000.
      Quantitation was based on the extracted ion chromatography (EIC) peak area
      signal, which was extracted at m/z 188.9515 with a mass extraction window (MEW)
      of 5ppm. The UHPLC/HRQMS method was validated based on International Conference
      on Harmonization (ICH) guidelines, which included selectivity, limit of detection
      (LOD), limit of quantitation (LOQ), repeatability, linearity, accuracy, and
      stability. 

PMID- 24309558
TI  - Management and outcome of diaphyseal aseptic non-unions of the lower limb: a
      systematic review.
AB  - OBJECTIVES: To review current treatments utilising biological enhancement
      modalities and their efficacy for the management of lower limb long bone aseptic
      non-unions. MATERIALS & METHODS: A systematic review of English articles using
      PubMed Medline; Ovid Medline; Embase; and the Cochrane Library was performed,
      supplemented by a manual search of bibliographies. RESULTS: Thirteen manuscripts
      met the inclusion criteria reporting on 428 patients. The overall healing had a
      pooled estimate of effect size at 94.3%. The calculated summarised estimate of
      effect size for deep infection rate (413 patients) was 2.3%. Three subgroups were
      then created on the basis of the exact type of graft used at the non-union site
      (ABG, BMP-7, BMP-7 + ABG). Comparison between the above subgroups revealed that
      ABG resulted in approximately 3-fold increase of the odds of healing compared
      with the use of BMP-7. Combined use of ABGs and BMP-7 improved the odds of
      healing by 3.5 times compared with BMP-7 alone. However, the previous median
      operations prior to the implantation of ABG or BMP-7 treatment was 1.09 versus
      2.3 respectively (p = 0.02). Although the implantation of ABG was associated with
      a greater incidence of infection the documented differences did not reach
      significance. CONCLUSIONS: Although ABG was found to have a higher success rate
      compared to BMP-7 (95% Vs 87%), patients treated with BMP-7 had a higher number
      of previous failed interventions, statistically significantly so (BMP-7 is used
      for the treatment of more recalcitrant non-unions). It is the surgeon's judgement
      that should determine the most suitable treatment modality, depending on the
      nature and characteristics (personality) of the non-union and the patient.

PMID- 24309560
TI  - Modeling optical signatures and excited-state reactivities of substituted
      hydroxyphenylbenzoxazole (HBO) ESIPT dyes.
AB  - The potential energy surfaces of dyes displaying strong excited-state
      intramolecular proton transfer (ESIPT) are investigated with the help of ab
      initio tools. It allows us to rationalize the interplay between the excited-state
      transition free energies and the observed optical signatures. 

PMID- 24309559
TI  - Aryl hydrocarbon receptor antagonism attenuates growth factor expression,
      proliferation, and migration in fibroblast-like synoviocytes from patients with
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease with high morbidity and
      mortality. Within the inflammatory milieu, resident fibroblast-like synoviocytes
      (FLS) in the synovial tissue undergo hyperplasia, which leads to joint
      destruction. Epidemiologic studies and our previous research suggest that
      activation of the aryl hydrocarbon receptor (AHR) pathway plays an instrumental
      role in the inflammatory and destructive RA phenotype. In addition, our recent
      studies implicate the AHR in the regulation of the expression of several growth
      factors in established tumor cell lines. Thus, under inflammatory conditions, we
      hypothesized that the AHR is involved in the constitutive and inducible
      expression of several growth factors, FLS proliferation and migration, along with
      protease-dependent invasion in FLS from patients with RA (RA-FLS). Treatment with
      the AHR antagonist GNF351 inhibits cytokine-induced expression of vascular
      endothelial growth factor-A (VEGF-A), epiregulin, amphiregulin, and basic
      fibroblast growth factor mRNA through an AHR-dependent mechanism in both RA-FLS
      and FLS. Secretion of VEGF-A and epiregulin from RA-FLS was also inhibited upon
      GNF351 treatment. RA-FLS cell migration, along with cytokine-induced RA-FLS cell
      proliferation, was significantly attenuated by GNF351 exposure. Treatment of RA
      FLS with GNF351 mitigated cytokine-mediated expression of matrix
      metalloproteinase-2 and -9 mRNA and diminished the RA-FLS invasive phenotype.
      These findings indicate that inhibition of AHR activity may be a viable
      therapeutic target in amelioration of disease progression in RA by attenuating
      growth factor release; FLS proliferation, migration, and invasion; and
      inflammatory activity. 

PMID- 24309561
TI  - Isolation and characterization of isochorismate synthase and cinnamate 4
      hydroxylase during salinity stress, wounding, and salicylic acid treatment in
      Carthamus tinctorius.
AB  - Salicylic acid (SA) is a prominent signaling molecule during biotic and abiotic
      stresses in plants biosynthesized via cinnamate and isochorismate pathways.
      Cinnamate 4-hydroxylase (C4H) and isochorismate synthase (ICS) are the main
      enzymes in phenylpropanoid and isochorismate pathways, respectively. To
      investigate the actual roles of these genes in resistance mechanism to
      environmental stresses, here, the coding sequences of these enzymes in safflower
      (Carthamus tinctorius), as an oilseed industrial medicinal plant, were partially
      isolated and their expression profiles during salinity stress, wounding, and
      salicylic acid treatment were monitored. As a result, safflower ICS (CtICS) and
      C4H (CtC4H) were induced in early time points after wounding (3-6 h). Upon
      salinity stress, CtICS and CtC4H were highly expressed for the periods of 6-24 h
      and 3-6 h after treatment, respectively. It seems evident that ICS expression
      level is SA concentration dependent as if safflower treatment with 1 mM SA could
      induce ICS much stronger than that with 0.1 mM, while C4H is less likely to be
      so. Based on phylogenetic analysis, safflower ICS has maximum similarity to its
      ortholog in Vitis vinifera up to 69%, while C4H shows the highest similarity to
      its ortholog in Echinacea angustifolia up to 96%. Overall, the isolated genes of
      CtICS and CtC4H in safflower could be considered in plant breeding programs for
      salinity tolerance as well as for pathogen resistance. 

PMID- 24309564
TI  - Cost-effectiveness of a genetic test for breast cancer risk.
AB  - Genetic testing of seven single-nucleotide polymorphisms (7SNP) can improve
      estimates of risk of breast cancer relative to the Gail risk test alone, for the
      purpose of recommending MRI screening for women at high risk. A simulation of
      breast cancer and health care processes was used to conduct a virtual trial
      comparing the use of the 7SNP test with the Gail risk test to categorize patients
      by risk. Average-risk patients received annual mammogram, whereas high-risk
      patients received annual MRI. Cancer incidence was based on Surveillance,
      Epidemiology, and End Results data and validated to Cancer Prevention Study II
      Nutrition Cohort data. Risk factor values were drawn from National Health and
      Nutrition Examination Survey (NHANES-4) and Prostate, Lung, Colorectal, and
      Ovarian Cancer Screening Trial data. Mammogram characteristics were derived from
      Breast Cancer Surveillance Consortium data. The test was most cost-effective when
      given to patients at an intermediate lifetime risk of breast cancer. For patients
      with a risk of 16% to 28%, it resulted in a 1.91% reduction in cancer deaths,
      saving 0.005 quality-adjusted life years per person at a cost of $163,264 per
      QALY. These results were sensitive to the age at which the test is given, the
      discount rate, and the costs of the genetic test and MRI. The cost effectiveness
      of using the 7SNP test for patients with intermediate Gail risk is similar to
      that of other recommended strategies, including annual MRI for patients with a
      lifetime risk greater than 20% or BRCA1/2 mutations.

PMID- 24309562
TI  - Broken nuclei--lamins, nuclear mechanics, and disease.
AB  - Mutations in lamins, which are ubiquitous nuclear intermediate filaments, lead to
      a variety of disorders including muscular dystrophy and dilated cardiomyopathy.
      Lamins provide nuclear stability, help connect the nucleus to the cytoskeleton,
      and can modulate chromatin organization and gene expression. Nonetheless, the
      diverse functions of lamins remain incompletely understood. We focus here on the
      role of lamins on nuclear mechanics and their involvement in human diseases.
      Recent findings suggest that lamin mutations can decrease nuclear stability,
      increase nuclear fragility, and disturb mechanotransduction signaling, possibly
      explaining the muscle-specific defects in many laminopathies. At the same time,
      altered lamin expression has been reported in many cancers, where the resulting
      increased nuclear deformability could enhance the ability of cells to transit
      tight interstitial spaces, thereby promoting metastasis. 

PMID- 24309563
TI  - The antidepressant desipramine and alpha2-adrenergic receptor activation promote
      breast tumor progression in association with altered collagen structure.
AB  - Emotional stress activates the sympathetic nervous system (SNS) and release of
      the neurotransmitter norepinephrine to promote breast tumor pathogenesis. We
      demonstrate here that the metastatic mammary adenocarcinoma cell line 4T1 does
      not express functional adrenergic receptors (AR), the receptors activated by
      norepinephrine, yet stimulation of adrenergic receptor in vivo altered 4T1 tumor
      progression in vivo. Chronic treatment with the antidepressant desipramine (DMI)
      to inhibit norepinephrine reuptake increased 4T1 tumor growth but not metastasis.
      Treatment with a highly selective alpha2-adrenergic receptor agonist,
      dexmedetomidine (DEX), increased tumor growth and metastasis. Neither
      isoproterenol (ISO), a beta-AR agonist, nor phenylephrine, an alpha1-AR agonist,
      altered tumor growth or metastasis. Neither DMI- nor DEX-induced tumor growth was
      associated with increased angiogenesis. In DMI-treated mice, tumor VEGF, IL-6,
      and the prometastatic chemokines RANTES, M-CSF, and MIP-2 were reduced. Tumor
      collagen microstructure was examined using second harmonic generation (SHG), a
      nonabsorptive optical scattering process to highlight fibrillar collagen. In DMI-
      and DEX-treated mice, but not ISO-treated mice, tumor SHG was significantly
      altered without changing fibrillar collagen content, as detected by
      immunofluorescence. These results demonstrate that alpha2-AR activation can
      promote tumor progression in the absence of direct sympathetic input to breast
      tumor cells. The results also suggest that SNS activation may regulate tumor
      progression through alterations in the extracellular matrix, with outcome
      dependent on the combination of adrenergic receptor activated. These results
      underscore the complexities underlying SNS regulation of breast tumor
      pathogenesis, and suggest that the therapeutic use of adrenergic receptor
      blockers, tricyclic antidepressants, and adrenergic receptor agonists must be
      approached cautiously in patients with breast cancer.

PMID- 24309567
TI  - National Association of Clinical Nurse Specialists Newsletter: President's
      Message.

PMID- 24309566
TI  - Case report and literature review of a dissecting thoracic aneurysm in a 16-year
      old boy presenting to the emergency department.
AB  - BACKGROUND: Aortic dissection is a rare occurrence in the pediatric and
      adolescent population. It has numerous etiologies, including congenital cardiac
      abnormalities. Aortic dissection has a high mortality rate; therefore, it is
      essential for the physician to at least consider this diagnosis in the setting
      this patient presented within their differential of atypical chest pain in the
      pediatric and adolescent population. STUDY OBJECTIVES: The purpose of this case
      is to consider an aortic dissection as part of the differential in a pediatric or
      adolescent patient presenting with atypical chest pain and abnormal vital signs.
      Second, this case demonstrates the diagnostic value of the D-dimer assay as a
      potential screening tool of aortic dissection. CASE REPORT: A 16-year-old boy
      with a benign past medical history presented to the Emergency Department (ED)
      with sudden onset of chest pain. His diagnostic workup led to a diagnosis of
      aortic dissection. It is noted that his D-dimer was significantly elevated.
      CONCLUSION: It is important to consider aortic dissection as a possibility when
      assessing the sick adolescent patient. The D-dimer is quite useful as a rapid and
      inexpensive test in the evaluation and stratification of adolescent chest pain
      patients in the ED.

PMID- 24309568
TI  - Evidence-based practice: the cochrane nursing care corner.

PMID- 24309569
TI  - Creating an enabling information technology infrastructure.
AB  - An enabling information technology platform is required to transform the
      healthcare system to one that is focused on improving value for patients. The key
      attributes of this platform are that it is patient centered, uses common data
      definitions, includes all types of patient data, is accessible to everyone
      involved in care of the patient, includes templates and experts systems, and is
      structured to facilitate information extraction. These attributes are described
      within the context of clinical nurse specialist practice. 

PMID- 24309570
TI  - Post-intensive care syndrome: preventing complications and improving long-term
      outcomes.

PMID- 24309571
TI  - Interdisciplinary research teams.

PMID- 24309572
TI  - Ketamine-a returning option for procedural sedation and analgesia in adults.
AB  - I am a clinical nurse specialist in a busy trauma center. Increasingly, we are
      using ketamine for procedures and pain management in adults. I thought ketamine
      was appropriate only for pediatric patients. Why has ketamine emerged again for
      adults? Also, we have seen a few cases of ketamine abuse over the past 3 months.
      Is ketamine abuse becoming more prevalent? 

PMID- 24309573
TI  - Nutritional interventions for liver-transplanted patients.

PMID- 24309574
TI  - Self-care in older adults with heart failure: an integrative review.
AB  - PURPOSE: The aims of this integrative review were to examine the evidence
      specific to self-care in older adults, 65 years or older, with heart failure and
      to indicate best nursing practice interventions for use in this population.
      ASSESSMENT: Self-care is a complex set of activities involving self-care
      maintenance and self-care management. Age-related and psychosocial factors impact
      older patients' ability to engage effectively in self-care practices. Although
      self-care processes are the focus of the investigation, few studies provide
      implications specific for the older adult population. Limited research on heart
      failure self-care in the older adult meets the age criterion of 65 years or
      older. METHODS: A comprehensive search of the literature was performed using
      Medline, CINAHL, and the Cochrane Library, as well as an ancestry approach of
      reference lists of selected studies. Eligible studies were randomized controlled
      trial, qualitative, quantitative, and mixed-method design studies on older adults
      with heart failure related to self-care for the years 2002-2012. FINDINGS: Three
      themes of self-care were noted in the selected studies: patient-related factors,
      patient education, and telemonitoring. The patient-related factors identified
      were barriers to self-care such as age-related symptoms, cognitive factors, and
      social issues. The interventions promoting self-care were patient education (self
      care knowledge) and telemonitoring (augmenting symptom recognition). Patient
      education tailored to older adults may be beneficial. Telemonitoring is an
      appropriate self-care enhancement tool for selected older adults. More emphasis
      needs to be placed on interventions to assist older adults with heart failure in
      symptom recognition and early notification of healthcare providers. CONCLUSIONS:
      As the population ages, a need for evidence-based care for older adults with
      heart failure is warranted. Heart failure self-care interventions do not address
      the special considerations of the older heart failure patient. To determine the
      best approaches for promoting effective self-care, older adults with heart
      failure need to be studied as a cohort. CLINICAL RELEVANCE: Older adults with
      heart failure face many challenges engaging in self-care practices. These older
      adults need individualized self-care instructions and home care follow-up.
      Identifying special needs of the patient, such as sensory or cognitive
      impairment, is necessary when providing instructions and follow-up care for the
      older adult.

PMID- 24309575
TI  - Clinical nurse specialists leading research to improve practice in the use of
      ankle blood pressure readings.
AB  - PURPOSE: The purpose of this article is to describe Clinical Nurse Specialist
      (CNS) practice as it relates to leadership in clinical research through the
      presentation of a study on ankle blood pressure (BP) measurements led by the CNS.
      BACKGROUND: Under the direction of the CNS, staff nurses engaged in the EBP
      process to explore the association between arm and ankle BP measurements. This
      EBP project led to a research study which was directed and led by the CNS.
      RATIONALE: CNS practice requires leadership in the areas of evidence-based
      practice and research. CNS leadership was critical to the success of the research
      project. DESCRIPTION: A descriptive study was undertaken which examined the
      agreement between upper extremity BP readings and ankle BP readings by comparing
      a series of three simultaneous ankle and arm BP readings on 174 subjects.
      CONCLUSION: Leading the research project elevated the CNS's visibility and
      influence within the organization by clearly demonstrating the value of the CNS
      in the research process and the impact nursing research has on nursing practice
      and patient outcomes.

PMID- 24309577
TI  - Increasing the odds, using peer review promotes successful abstract submission.
AB  - PURPOSE/OBJECTIVES: Supporting clinical nurses to participate in professional
      growth and development is rewarding and grooms our future leaders. This is
      especially true during Magnet designation, as the bar gets higher. This article
      provides the structure and process required to develop a clinical nurse
      specialist-led peer review abstract workshop. BACKGROUND: Abstract writing is
      complex. It is a self-contained summary of completed work in only a few words.
      Writing winning abstracts for submission at local, regional, and national
      conferences can be a daunting task, but using peer review provides the author
      with guidance, self-assurance, peer support, and encouragement. RATIONALE:
      Clinical nurse specialists, as expert clinician, consultant, educator, and
      researcher, influence organizational outcomes across the 3 spheres of influence,
      reducing hospital-acquired complications and improving patient outcomes. Clinical
      nurse specialists need to mentor nurses in disseminating these outcomes at
      nursing conferences. DESCRIPTION: A 3-part workshop was designed to give the
      participants time to bring to light their ideas, put them on paper, and receive
      valuable peer feedback. In the first session, the ground rules are set. In the
      second session, the first draft is reviewed and constructive peer review is
      provided. In the final session, the abstract is polished and it is ensured that
      the abstract is complete, concise, clear and cohesive. OUTCOME: Implementing an
      abstract workshop provides opportunities to enhance team building and
      collaboration skills. It provides peer support and encouragement as well as
      generates innovating ideas. CONCLUSION: Implementing an abstract workshop sets
      the stage for successful abstract submission while ensuring that participants are
      prepared and ready for the challenge. This type of format can be used globally or
      on individual units and tailored for the needs and interests of the participants.
      IMPLICATIONS: The process used for developing an abstract workshop serves as a
      template to implement in any setting.

PMID- 24309576
TI  - Retention strategies in longitudinal studies with emerging adults.
AB  - PURPOSE/OBJECTIVES: The purpose of this report was to describe retention
      strategies that were useful and those that were not in a longitudinal study of
      emerging adults. BACKGROUND: A longitudinal study examining the transition to
      young adulthood among emerging adults with type 1 diabetes, which had success in
      retention, provided the context for describing retention strategies. RATIONALE: A
      challenge in longitudinally designed studies is retention of participants because
      the loss decreases power for statistical analysis. Given that emerging adulthood
      is a period of instability, retention is particularly challenging among this
      population. However, longitudinal studies are the best way to understand
      developmental changes, and it is also important to increase our knowledge of
      health outcomes during emerging adulthood. DESCRIPTION: Retention strategies used
      in the study are described, including promoting a positive relationship with
      participants, maintaining contact with participants, having a study staff with
      good interpersonal skills, using incentives, conveying respect for participants,
      and using user-friendly data collection. OUTCOMES: Useful strategies to promote a
      positive relationship included sending cards and newsletters to participants,
      maintaining consistency of contact person, and expressing appreciation for
      participant's time and effort. Useful strategies for maintaining contact with
      participants included obtaining contact information at every data collection
      point, maintaining birth dates and chart numbers in tracking databases,
      monitoring returned mail, and using Web search engines. Other useful strategies
      were providing incentives to participants, employing staff with good
      interpersonal skills, providing participants with choices when appropriate, and
      using user-friendly data collection. One strategy, using contests, was not found
      useful. CONCLUSIONS: Despite the challenges of conducting longitudinally designed
      studies with emerging adults, multiple retention strategies can be used that are
      useful to retention. IMPLICATIONS: It is feasible to conduct longitudinal studies
      with emerging adults despite the challenges.

PMID- 24309578
TI  - Utilization of national patient registries by clinical nurse specialist:
      opportunities and implications.
AB  - PURPOSE: The purpose of this article was to describe how clinical nurse
      specialists can be instrumental in getting involved in the process of joining a
      national disease registry to improve patient outcomes. BACKGROUND: Clinical
      patient data registries provide longitudinal data on developmental outcomes in
      chronic, lifelong diseases affecting children. Recognition and application of
      their use have historically allowed for collection of benchmarking data, improved
      understanding of disease processes and patient outcomes, and improved quality of
      life. DESCRIPTION OF THE PROJECT: A group of advanced practice nurses in a
      university-based multispecialty clinic, through evidence-based practice, embarked
      on the process of joining the National Spina Bifida Patient Registry sponsored by
      the Centers for Disease Control and Prevention. OUTCOME: By taking the lead as
      project managers, this group of advanced practice nurses obtained buy-in from
      physicians and multispecialty team members of the Spina Bifida Clinic in the
      university children's hospital where they practice. An institutional review board
      application was submitted to their university children's hospital internal review
      board and currently approved. CONCLUSION: This project demonstrates how dynamic
      utilization of core competencies through application of specific knowledge and
      skill sets supports the advanced practice nurse's instrumental role in actively
      initiating, promoting, and supporting participation in clinical patient data
      registries that seek improved patient outcomes at the national level.
      IMPLICATIONS: Clinical nurse specialists quantify their role and purpose when
      connecting their interventions and influence to patient outcomes with utilization
      of resources, such as a national patient data registry.

PMID- 24309579
TI  - Assessing clinical staff learning needs, part 1: structure and process for
      clinical nurse specialist student projects.

PMID- 24309580
TI  - Clinical nurse specialist profile.

PMID- 24309581
TI  - Art, body, and soul: a conversation with David Clegg.

PMID- 24309582
TI  - Achieving specialty competency for clinical nurse specialists: a position paper
      (released september 13, 2013).

PMID- 24309583
TI  - Neutrophils: the dawn of a new era? Preface.

PMID- 24309584
TI  - Early aphasia rehabilitation is associated with functional reactivation of the
      left inferior frontal gyrus: a pilot study.
AB  - BACKGROUND AND PURPOSE: Early poststroke aphasia rehabilitation effects and their
      functional MRI (fMRI) correlates were investigated in a pilot, controlled
      longitudinal study. METHODS: Twelve patients with mild/moderate aphasia (8 Broca,
      3 anomic, and 1 Wernicke) were randomly assigned to daily language rehabilitation
      for 2 weeks (starting 2.2 [mean] days poststroke) or no rehabilitation. The
      Aachen Aphasia Test and fMRI recorded during an auditory comprehension task were
      performed at 3 time intervals: mean 2.2 (T1), 16.2 (T2), and 190 (T3) days
      poststroke. RESULTS: Groups did not differ in terms of age, education, aphasia
      severity, lesions volume, baseline fMRI activations, and in task performance
      during fMRI across examinations. Rehabilitated patients significantly improved in
      naming and written language tasks (P<0.05) compared with no rehabilitation group
      both at T2 and T3. Functional activity at T1 was reduced in language-related
      cortical areas (right and left inferior frontal gyrus and middle temporal gyrus,
      right inferior parietal lobule and superior temporal gyrus) in patients compared
      with controls. T2 and T3 follow-ups revealed a cortical activation increase, with
      significantly greater activation in the left hemisphere areas in rehabilitated
      patients at T2 and T3, and a time*treatment effect at T2 in the left inferior
      Broca area after rehabilitation. Left inferior frontal gyrus activation at T2
      significantly correlated with naming improvement. CONCLUSIONS: Early poststroke
      aphasia treatment is useful, has durable effects, and may lead to early enhanced
      recruitment of brain areas, particularly the left inferior frontal gyrus, which
      persists in the chronic phase.

PMID- 24309585
TI  - Comparison of clinical risk stratification for predicting stroke and
      thromboembolism in atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Several accepted algorithms exist to characterize the
      risk of thromboembolism in atrial fibrillation. We performed a comparative
      analysis to assess the predictive value of 9 such schemes. METHODS: In a
      longitudinal community-based cohort study from Olmsted County, Minnesota, 2720
      residents with atrial fibrillation were followed up for 4.4+/-3.6 years+/-SD from
      1990 to 2004. Risk factors were identified using a diagnostic index integrated
      with the electronic medical record. Thromboembolism and cardiovascular event data
      were collected and analyzed. RESULTS: We identified 350 validated thromboembolic
      events in our cohort. Multivariable analysis identified age >75 years (odds
      ratio, 2.08; P<0.0001), female sex (odds ratio, 1.45; P=0.0015), history of
      hypertension (odds ratio, 3.07; P<0.0001), diabetes mellitus (odds ratio, 1.58;
      P=0.0003), and history of heart failure (odds ratio, 1.50; P=0.0102) as
      significant predictors of clinical thromboembolism. The Stroke Prevention in
      Atrial Fibrillation (SPAF; hazard ratio, 2.75; c=0.659), CHADS2-revised (hazard
      ratio, 3.48; c=0.654), and CHADS2-classical (hazard ratio, 2.90; c=0.653) risk
      schemes were most accurate in risk stratification. The low-risk cohort within the
      CHA2DS2-VASc scheme had the lowest event rate among all low-risk cohorts (0.11
      per 100 person-years). CONCLUSIONS: A direct comparison of 9 risk schemes reveals
      no profound differences in risk stratification accuracy for high-risk patients.
      Accurate prediction of low-risk patients is perhaps more valuable in determining
      those unlikely to benefit from oral anticoagulation therapy. Among our cohort,
      CHA2DS2-VASc performed best in this purpose.

PMID- 24309586
TI  - Transient global amnesia and the risk of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Whether transient global amnesia (TGA) represents an
      arterial insult that heralds ischemic stroke remains unclear. Therefore, we
      examined stroke risk after TGA in a population-based cohort. METHODS: After
      performing chart review at our institution to validate the International
      Classification of Diseases, 9th Edition, Clinical Modification diagnosis code for
      TGA, we used administrative claims data to identify all patients discharged from
      nonfederal California emergency departments or acute care hospitals between 2005
      and 2010 with a primary discharge diagnosis of TGA. Patients with a primary
      discharge diagnosis of migraine, seizure, or transient ischemic attack were
      included as controls. Kaplan-Meier statistics were used to calculate rates of
      ischemic stroke, and Cox proportional hazards analyses were used to compare
      stroke risk among the 4 exposure groups while controlling for traditional stroke
      risk factors. RESULTS: International Classification of Diseases, 9th Edition,
      Clinical Modification code 437.7 had a sensitivity of 86% and a specificity of
      95% for TGA. The cumulative 1-year rate of stroke was 0.54% (95% confidence
      interval [CI], 0.36-0.81) after TGA, 0.22% (95% CI, 0.20-0.25) after migraine,
      0.90% (95% CI, 0.83-0.97) after seizure, and 4.72% (95% CI, 4.60-4.85) after
      transient ischemic attack. After adjustment for demographic characteristics and
      stroke risk factors, TGA was not associated with stroke risk when compared with
      migraine (hazard ratio, 0.82; 95% CI, 0.61-1.10). The likelihood of stroke after
      TGA was lower than after seizure (hazard ratio, 0.57; 95% CI, 0.44-0.76) or
      transient ischemic attack (hazard ratio, 0.27; 95% CI, 0.20-0.35). CONCLUSIONS:
      Compared with patients diagnosed with migraine or seizure, patients diagnosed
      with TGA do not seem to face a heightened risk of stroke.

PMID- 24309588
TI  - Coal as an abundant source of graphene quantum dots.
AB  - Coal is the most abundant and readily combustible energy resource being used
      worldwide. However, its structural characteristic creates a perception that coal
      is only useful for producing energy via burning. Here we report a facile approach
      to synthesize tunable graphene quantum dots from various types of coal, and
      establish that the unique coal structure has an advantage over pure sp2-carbon
      allotropes for producing quantum dots. The crystalline carbon within the coal
      structure is easier to oxidatively displace than when pure sp2-carbon structures
      are used, resulting in nanometre-sized graphene quantum dots with amorphous
      carbon addends on the edges. The synthesized graphene quantum dots, produced in
      up to 20% isolated yield from coal, are soluble and fluorescent in aqueous
      solution, providing promise for applications in areas such as bioimaging,
      biomedicine, photovoltaics and optoelectronics, in addition to being inexpensive
      additives for structural composites.

PMID- 24309589
TI  - Intense ultraviolet upconversion emission from water-dispersed colloidal
      YF3:Yb3+/Tm3+ rhombic nanodisks.
AB  - Intense ultraviolet upconversion emission has been observed in water-dispersed
      uniform rhombic nanodisks (side length of ~14 nm and thickness of ~2.5 nm) of YF3
      co-doped with Yb(3+) sensitizer and Tm(3+) activator ions, when excited at ~980
      nm.

PMID- 24309590
TI  - A lower lip mass.

PMID- 24309591
TI  - "If they can't tell the difference between duphalac and digoxin you've got
      patient safety issues". Nurse Lecturers' constructions of students' dyslexic
      identities in nurse education.
AB  - AIM: The paper explores how student nurses with a dyslexic identity were
      discursively constructed by lecturing staff in nurse education. BACKGROUND: An
      increasing number of students completing programmes of study in higher education
      are registering and disclosing one or more disabilities to their respective
      institutional support services. As students with dyslexia enter the nursing
      profession, they bring with them their own unique identity that situates their
      disability in a specific light. Nurse lecturers play an integral role in
      supporting all students including those with a disability; however no previous
      research has attempted to examine the language they use to construct students
      with a dyslexic identity. Critically, the internalised views of those with
      teaching and learning responsibilities who directly interact with students with
      disabilities have a critical influence on the nature of the supports provided, as
      well as decisions about students' professional competence. DESIGN: Discussions
      that centre on the inclusion of individuals with disability in healthcare
      education are shaped by language and diverse ways of understanding, therefore, an
      exploratory discursive design, examining how dyslexic identities are socially
      constructed by nurse lecturers is an overarching focus of the paper. Using
      narrative interviewing, twelve nurse lecturers from two higher education
      institutions in the Republic of Ireland were interviewed during the period
      February to July 2012. RESULTS: Discourse analysis was guided by a narrative
      discursive approach. Nurse lecturers identified 'Getting the work done' as a
      critical component to becoming a nurse, where expectations associated with
      efficiency and independence superseded students' right to accommodation. An
      implicit mild-severe binary existed amongst lecturers while categorising students
      with dyslexia, with those placed in the latter considered professionally
      unsuitable. These concerns are individually critiqued. CONCLUSION: Critically,
      policy leaders must continue to consider wider sociocultural as well as
      individualised understandings of dyslexic identities in order to enhance
      inclusion prerogatives.

PMID- 24309592
TI  - Genetics of the ergot fungus Claviceps purpurea : I. Proof of a monoecious life
      cycle and segregation patterns for mycelial morphology and alkaloid production.
AB  - The morphological and physiological evaluation of single ascorspore lines (F1)
      obtained from 4 production strains of Claviceps purpurea and the subsequent
      production and evaluation of an F2 from two of these strains has shown: 1. The
      breeding system responsible for the sexual cycle of C. purpurea is characterized
      by monoecism and self-compatibility. 2. Heterokaryosis is neither required for
      the completion of the life cycle nor for alkaloid synthesis. 3. The huge
      variability in both mycelial morphology and alkaloid spectra makes it evident
      that all production strains are highly heterogeneous. 4. A correlation between
      morphology and an alkaloid pattern was not found. 5. Alkaloid production is,
      however, correlated with distinct genotypes. 6. In some cases an increase in the
      total alkaloid content and in the formation of specific alkaloids was also found,
      showing that the genetic control of these metabolites may be accessible. Taken
      together these results open up the way to concerted breeding with Claviceps
      purpurea with the object of improving alkaloid production. 

PMID- 24309593
TI  - The activity of aldolase, aspartate aminotransferase and the level of glucose in
      the blood plasma of chickens of various breeds and crossbreds.
AB  - Studies on the activity of aldolase, aspartate aminotransferase and on the level
      of glucose in the blood serum of chickens from various breeds and crossbreds have
      shown that: 1. Breed and sex had a significant influence on the level of glucose
      and the activity of aldolase and aspartate aminotransferase. 2. The highest level
      of glucose was observed in both sexes of White Rock chickens; the lowest in
      Greenleg hens and Leghorn cocks. 3. The highest activity of aldolase was observed
      in White Rock cocks and Plymouth Rock hens; the lowest in Greenleg hens and
      Leghorn cocks. 4. The highest activity of aspartate aminotransferase was observed
      in White Rock chickens; the lowest in Leghorns. 5. As regards the traits
      investigated, crossbreds, in comparison to the parental breeds, were
      characterised in a majority of cases by values intermediate or only slightly
      different. Cases of homosis and heterosis in the level of the physiological
      indicators examined were also observed. 

PMID- 24309594
TI  - Regulation of gene action in Petunia hybrida: Unstable alleles of a gene for
      flower colour.
AB  - In a progeny of a selfed individual of the dark red-flowered cultivar 'Roter
      Vogel' some white-flowered plants appeared as the result of a mutation of the
      genetic factor Anl involved in anthocyanin synthesis. The white flowers of these
      plants had red spots owing to back-mutations in the dermal cells of the young
      corolla.Owing to a striking unstability of the new allele of Anl, a number of
      mutants originated which differ mutually in the frequency of reversion, which
      expressed itself in the very substantial differences in the spot density of the
      limb of the corolla. Between a mean number of less than one spot per cm(2) of the
      limb and a mean number of over 10.000 spots/cm(2), a series of transitions was
      found.The reversions did not remain restricted to the young epidermis but also
      occurred in sporogenous tissues. This resulted in the appearance of selfcoloured
      red descendants of plants with red-spotted white flowers. There is a positive
      correlation between the spot density of the parent plants and the percentage of
      plants with completely red corollas.The red spots on the corolla usually have the
      same colour as the wild type ('Roter Vogel'), but occasionally mutants occur with
      paler spots, the colour varying from a very pale pink to a red nearly as deep as
      in the wild type. The selfcoloured descendants of such mutants also show this
      colour variation from pale pink to red.On the grounds of these observations a
      theory was formulated which postulates that the Anl locus consists of a
      structural gene responsible for an enzyme active during anthocyanin synthesis and
      a regulatory element built up from intermediate repetitive DNA. This regulatory
      element in turn is built up of two components, one of which, the 'mutator',
      decides the activation of the structural gene while the other, the 'expressor',
      modifies the rate of activation. The mutations must be considered representative
      of larger or smaller deletions within one or both of these components. Reversions
      are the result of the restoration of the deletions by means of an amplification
      of the repetitive DNA in dividing cells of the developing flower buds. 

PMID- 24309595
TI  - A 9 * 9 diallel analysis in peanuts (A. hypogaea L.): Flowering time, tops'
      weight, pod yield per plant and pod weight.
AB  - Four quantitative traits were studied by analysing F2 data derived from a 9 * 9
      diallel cross utilizing widely divergent, inbred, erect cultivars of peanuts, A.
      hypogaea. Bidirectional dominance was found in the traits total pod yield per
      plant and number of days from planting to first flower; in pod size, the alleles
      giving small pods were consistently dominant and for high tops' weight, dominance
      and overdominance were found. The high heritability of pod yield/plant (0.79)
      indicates that breeding for higher yield/plant can succeed if large F2
      populations are grown and rigorous visual selection combined with progeny testing
      are employed. The genetic correlations of pod yield/plant with other traits were
      low. Breeding for plants with large (jumbo) pods can be aided by the fact that
      they are homozygous recessive, or nearly so. Simultaneous breeding for high
      yields and large pods is possible: there was a positive (but low) genetic
      correlation between the two (0.16). A modification by which less biased estimates
      of the number of effective factors can be obtained and a possible relationship
      between bidirectional dominance and genic interaction were proposed. 

PMID- 24309596
TI  - Investigations of the seed protein content of several pea genotypes grown in two
      different years.
AB  - Seventeen X-ray and neutron induced mutants of the commercial variety 'Dippes
      gelbe Victoria' were analyzed with regard to their seed protein percentage. The
      interaction of genotypic and year effects in 1975 (normal weather conditions) and
      1976 (extremely hot and dry) was also taken into consideration. To avoid
      undiscoverable environmental bias, the plants were grown in a nonstandard three
      dimensional layout. Biometric analysis was done by using the theory of the
      general linear model with a formula-processing computer program. In the first
      year, significant genetically caused differences were found in the material. The
      bifurcated mutant 157A was especially of considerable interest because an
      improved protein content was combined with relative good yield. In the second
      year, no significant differences between the mutants were revealed, but all
      genotypes showed a similar good protein value of about 27%. 

PMID- 24309597
TI  - The reciprocal interaction between autophagic dysfunction and ER stress in
      adipose insulin resistance.
AB  - Autophagy, a predominantly cytoprotective process, is an important regulator in
      diabetic metabolism and endoplasmic reticulum (ER) stress responses. However, the
      interaction and biological significance between autophagic imbalance and ER
      stress involved in insulin resistance remain not fully elucidated. In the present
      study, when compared with normal glucose tolerance (NGT) subjects, enhanced ER
      stress and pronounced protein and mRNA levels of the autophagic genes such as
      Atg7, LC3A, and LC3B were evident in adipose tissue of patients with type 2
      diabetes. An increased number of autophagosomes and elevated autophagy flux in
      adipose explants incubated with lysomoal inhibitor were also observed in type 2
      diabetes. In addition, adipocytes differentiation was significantly repressed by
      exogenous ER stress and defective autophagy in vitro. Tunicamycin-induced ER
      stress in adipocytes can trigger autophagic response and insulin insensitivity
      that was partially attributed to the upregulation of IRE1-JNK pathway, whereas
      autophagy deficiency resulted in ER stress and impaired insulin signaling,
      further supporting the crucial roles of autophagy in ER stress and insulin
      resistance. Moreover, disturbance of autophagy and insulin sensitivity induced by
      tunicamycin can be effectively corrected by the addition of osteocalcin in an
      NFkappaB-dependent manner in vitro. In conclusion, our results demonstrated a
      reciprocal functional interaction among autophagy, ER stress, and insulin
      signaling in adipose tissue of type 2 diabetes and adipocytes, supporting an
      adaptive role of autophagy-dependent mechanism in response to ER stress-induced
      insulin resistance in type 2 diabetes. 

PMID- 24309598
TI  - A novel APC gene mutation associated with a severe phenotype in a patient with
      Turcot syndrome.
AB  - Turcot syndrome is a rare inherited condition of colonic polyposis associated
      with central nervous system tumors. We report a patient with a novel adenomatous
      polyposis coli gene mutation leading to a severe phenotype including
      medulloblastoma, low-grade fibromyxoid sarcoma following cranial radiation,
      pilomatrixomas, colonic adenomas, and abdominal desmoid tumor following
      colectomy, all of which were successfully treated. Multiple tumors may be seen in
      patients with Turcot syndrome but the occurrence of sarcomas is rare. This case
      highlights the importance of close follow-up for patients with Turcot syndrome
      and the importance of a broad differential diagnosis in evaluating a condition in
      which multiple tumors are frequently seen. 

PMID- 24309587
TI  - Factors influencing the decline in stroke mortality: a statement from the
      American Heart Association/American Stroke Association.
AB  - BACKGROUND AND PURPOSE: Stroke mortality has been declining since the early 20th
      century. The reasons for this are not completely understood, although the decline
      is welcome. As a result of recent striking and more accelerated decreases in
      stroke mortality, stroke has fallen from the third to the fourth leading cause of
      death in the United States. This has prompted a detailed assessment of the
      factors associated with the change in stroke risk and mortality. This statement
      considers the evidence for factors that have contributed to the decline and how
      they can be used in the design of future interventions for this major public
      health burden. METHODS: Writing group members were nominated by the committee
      chair and co-chair on the basis of their previous work in relevant topic areas
      and were approved by the American Heart Association Stroke Council's Scientific
      Statements Oversight Committee and the American Heart Association Manuscript
      Oversight Committee. The writers used systematic literature reviews, references
      to published clinical and epidemiological studies, morbidity and mortality
      reports, clinical and public health guidelines, authoritative statements,
      personal files, and expert opinion to summarize evidence and to indicate gaps in
      current knowledge. All members of the writing group had the opportunity to
      comment on this document and approved the final version. The document underwent
      extensive American Heart Association internal peer review, Stroke Council
      leadership review, and Scientific Statements Oversight Committee review before
      consideration and approval by the American Heart Association Science Advisory and
      Coordinating Committee. RESULTS: The decline in stroke mortality over the past
      decades represents a major improvement in population health and is observed for
      both sexes and for all racial/ethnic and age groups. In addition to the overall
      impact on fewer lives lost to stroke, the major decline in stroke mortality seen
      among people <65 years of age represents a reduction in years of potential life
      lost. The decline in mortality results from reduced incidence of stroke and lower
      case-fatality rates. These significant improvements in stroke outcomes are
      concurrent with cardiovascular risk factor control interventions. Although it is
      difficult to calculate specific attributable risk estimates, efforts in
      hypertension control initiated in the 1970s appear to have had the most
      substantial influence on the accelerated decline in stroke mortality. Although
      implemented later, diabetes mellitus and dyslipidemia control and smoking
      cessation programs, particularly in combination with treatment of hypertension,
      also appear to have contributed to the decline in stroke mortality. The potential
      effects of telemedicine and stroke systems of care appear to be strong but have
      not been in place long enough to indicate their influence on the decline. Other
      factors had probable effects, but additional studies are needed to determine
      their contributions. CONCLUSIONS: The decline in stroke mortality is real and
      represents a major public health and clinical medicine success story. The
      repositioning of stroke from third to fourth leading cause of death is the result
      of true mortality decline and not an increase in mortality from chronic lung
      disease, which is now the third leading cause of death in the United States.
      There is strong evidence that the decline can be attributed to a combination of
      interventions and programs based on scientific findings and implemented with the
      purpose of reducing stroke risks, the most likely being improved control of
      hypertension. Thus, research studies and the application of their findings in
      developing intervention programs have improved the health of the population. The
      continued application of aggressive evidence-based public health programs and
      clinical interventions is expected to result in further declines in stroke
      mortality.

PMID- 24309599
TI  - Glioblastoma multiforme arising from dysembryoplastic neuroepithelial tumor in a
      child in the absence of therapy.
AB  - Dysembryoplastic neuroepithelial tumors (DNETs) are considered as low-grade
      tumors commonly associated with intractable seizures. We report a case of an
      unusual hemispheric DNET in a young child presenting with new-onset focal
      seizures. The tumor was notable for its atypical neuroimaging features and very
      rapid malignant transformation into a glioblastoma multiforme in the absence of
      radiation or chemotherapy, 1-year postdiagnosis. Our case highlights the
      malignant potential of atypical DNETs in the absence of therapy. 

PMID- 24309600
TI  - Hearing loss during osteosarcoma chemotherapy: when acute ifosfamide toxicity
      revealed unnoticed methotrexate encephalopathy.
AB  - Ifosfamide and methotrexate are widely used for the treatment of pediatric
      osteosarcoma. However, both these chemotherapeutic drugs can cause
      encephalopathy. A 17-year-old girl presented with profound hearing loss and
      dizziness during a postoperative course of ifosfamide, 20 days after a course of
      methotrexate. Cerebral magnetic resonance imaging (MRI) showed bilateral white
      matter hypersignal in Fluid Attenuated Inversion Recovery sequences. The clinical
      evolution was rapidly favorable after methylene blue infusion. This is the second
      reported case of acute deafness, possibly associated with ifosfamide, whereas MRI
      data revealed unnoticed chronic methotrexate toxicity. Systematic MRI screening
      and hearing evaluation may be useful in such cases. 

PMID- 24309601
TI  - Both hemophilia health care providers and hemophilia a carriers report that
      carriers have excessive bleeding.
AB  - INTRODUCTION: Hemophilia A, the result of reduced factor VIII activity, is an X
      linked recessive bleeding disorder. Previous reports of hemophilia A carriers
      suggest an increased bleeding tendency. Our objective was to determine the
      attitudes and understanding of the hemophilia A carrier bleeding phenotype, and
      opinions regarding timing of carrier testing from the perspective of both medical
      providers and affected patients. Data from this survey were used as preliminary
      data for an ongoing prospective study. MATERIALS AND METHODS: An electronic
      survey was distributed to physicians and nurses employed at Hemophilia Treatment
      Centers, and hemophilia A carriers who were members of Hemophilia Federation of
      America. The questions focused on the clinical understanding of bleeding symptoms
      and management of hemophilia A carriers, and the timing and intensity of carrier
      testing. RESULTS: Our survey indicates that 51% (36/51) of providers compared
      with 78% (36/46) of carriers believe that hemophilia A carriers with normal
      factor VIII activity have an increased bleeding tendency (P<0.001); 72% (33/36)
      of hemophilia A carriers report a high frequency of bleeding symptoms. Regarding
      carrier testing, 72% (50/69) of medical providers recommend testing after 14
      years of age, conversely 65% (29/45) of hemophilia A carriers prefer testing to
      be done before this age (P<0.001). DISCUSSION: Hemophilia A carriers self-report
      a higher frequency of bleeding than previously acknowledged, and have a
      preference for earlier testing to confirm carrier status.

PMID- 24309602
TI  - Single-agent cisplatin treatment of children with high-risk hepatoblastoma.
AB  - PURPOSE: The use of neoadjuvant chemotherapy has improved the survival of
      patients with hepatoblastoma (HB). However, an increased number of treatment
      complications and toxic deaths, particularly from heart failure, have been
      observed with doxorubicin treatment. We have applied cisplatin as a single agent
      to treat children with high-risk HB to improve event-free survival (EFS).
      METHODS: Between 2007 and 2009, 14 patients with untreated high-risk HB were
      enrolled in this study. All the patients received a single-agent treatment of
      cisplatin. The initial cisplatin cycle was administered in a continuous
      intravenous 24-hour infusion of 80 mg/m/24 h. The primary outcome was the rate of
      complete resection. Secondary outcomes were EFS and overall survival (OS).
      RESULTS: Eleven patients (78.6%) had an overall partial response. Two patients
      (14.3%) had stable disease. One patient experienced (7.1%) progression. Of the 4
      patients who presented with lung metastases initially, 1 patient achieved
      complete response, 2 patients achieved partial response, and 1 patient
      experienced progression during preoperative chemotherapy. The complete resection
      rate was 78.6% (95% CI, 49%-95%). The Kaplan-Meier estimates of 2-year EFS and OS
      for the whole group were 64.3% (95% CI, 35%-87%) and 85.7% (95% CI, 57%-98%),
      respectively. The 2-year EFS and OS rates of patients who achieved complete
      resection were 81.8% (95% CI, 48%-98%) and 100% (95% CI, 62%-100%), respectively.
      CONCLUSIONS: The single-agent cisplatin had less toxicity than cisplatin plus
      doxorubicin and achieved an equal rate of complete resection in high-risk HB
      compared with conventional multiagent chemotherapy.

PMID- 24309603
TI  - Persistent pulmonary hypertension of the newborn associated with severe
      congenital anemia of various etiologies.
AB  - Among the many associated features of persistent pulmonary hypertension of the
      neonate (PPHN), severe congenital anemia has been described only occasionally and
      is not included in the list of conditions that may cause PPHN in the neonate. We
      describe the clinical course of a group of 12 full-term neonates with PPHN and
      congenital anemia due to congenital dyserythropoietic anemia (7/12), alpha
      thalasemia (1/12), Diamond-Blackfan (1/12), and epsilon gamma delta beta
      thalassemia (3/12). The association of congenital anemia and PPHN is more common
      than previously thought; it can exist with various etiologies and severity of
      anemia. Congenital anemia has not been described until now as a cause or risk
      factor for PPHN; it should be considered as such alone or in combination with
      other known causes to be recognized early and treated appropriately to improve
      outcome. In families with known cases of congenital anemia due to the above
      mentioned diagnosis, closer prenatal follow-up should be offered to anticipate
      possible fetal distress and/or fetal anemia and PPHN after birth.

PMID- 24309604
TI  - Successful treatment of Kasabach-Merritt phenomenon arising from Kaposiform
      hemangioendothelioma by sirolimus.

PMID- 24309605
TI  - Predictors of bacteremia among children with sickle cell disease presenting with
      fever.
AB  - INTRODUCTION: Bacterial sepsis is more common and potentially life threatening in
      children with sickle cell disease (SCD). Identification of variables that predict
      bacteremia may aid clinicians in recognizing patients with SCD at higher risk for
      sepsis. OBJECTIVE: To determine whether absolute neutrophil count (ANC) >20*10/L
      is an independent risk factor for bacteremia in children with SCD and to identify
      other predictors of bacteremia in this population. METHODS: A case-control study
      was conducted. Subjects were 0 to 18 years of age admitted to a tertiary care
      pediatric hospital over a 17-year period with SCD and fever at presentation.
      Cases had bacteremia, whereas controls had negative blood cultures. RESULTS: Data
      were analyzed for 40 cases and 120 controls. ANC>20*10/L was significantly more
      prevalent among cases (odds ratio [OR], 7.0; 95% confidence interval [CI], 2.6
      18.9). Cases were more likely to have emesis (OR, 2.9; 95% CI, 1.0-8.4) and a
      higher proportion of band cells (OR, 1.3; 95% CI, 1.1-1.4) at presentation.
      CONCLUSIONS: In a febrile child with SCD, an ANC>20*10/L, a higher proportion of
      band cells, and the presence of vomiting were associated with an increased
      likelihood of bacteremia.

PMID- 24309606
TI  - Monoallelic mutations of the perforin gene may represent a predisposing factor to
      childhood anaplastic large cell lymphoma.
AB  - Anaplastic large cell lymphoma (ALCL) accounts for approximately 15% of all
      pediatric non-Hodgkin lymphomas. It has distinct clinical features, including
      frequent involvement of extranodal sites and rare localization to the central
      nervous system. As some presenting features of ALCL are in common with the
      hemophagocytic syndrome, we previously analyzed a small series of patients with
      ALCL for PRF1 mutations and found that 27% of them carried mutations. We now
      expanded our preliminary study by increasing the cohort of ALCL patients to a
      total of 84 consecutive cases, in whom we extended mutation analysis to the genes
      SH2D1A, PRF1 e UNC13D, all related to familial HLH. Furthermore, perforin
      expression in tumor cells was investigated on paraffin-embedded tissues by
      immunohistochemical analysis. Mutations were observed in 23/84 patients (27.4%).
      Twenty-one patients (25%) carried a total of 10 different mutations of PRF1; they
      were monoallelic in 20 patients, biallelic in 1. No mutations were found in the
      gene SH2D1A. Two additional patients had missense mutations of the UNC13D gene.
      These data show that monoallelic germline mutations of PRF1 are frequent in
      patients with childhood ALCL, suggesting that partially impaired cytotoxic
      machinery may represent a predisposing factor for ALCL. Involvement is less
      frequent for UNC13D and absent for SH2D1A. 

PMID- 24309607
TI  - In reply: Propofol and additives in studies evaluating inflammatory responses.

PMID- 24309608
TI  - Evidence-based nonpharmacologic interventions for pediatric pain: an editorial
      commentary.

PMID- 24309609
TI  - Pediatric phase II trials of poly-ICLC in the management of newly diagnosed and
      recurrent brain tumors.
AB  - Brain tumors are the most common solid tumor diagnosed in childhood that account
      for significant morbidity and mortality. New therapies are urgently needed;
      hence, we conducted the first ever prospective open-label phase II trials of the
      biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC
      is a synthetic double-stranded RNA that has direct antiviral, antineoplastic, and
      immune adjuvant effects. A total of 47 children representing a variety of brain
      tumor histopathologic subtypes were treated with poly-ICLC. On the basis of the
      results of the initial phase II trial, an expanded prospective phase II trial in
      low-grade glioma (LGG) has been initiated. MRI was used to acquire volume-based
      measures of tumor response. No dose-limiting toxicities have been observed. In
      the initial study 3 of 12 subjects with progressive high-grade gliomas (HGGs)
      responded, and 2 of 4 children with progressive LGG experienced stable disease
      for 18 to 24 months. In the follow-up LGG phase II study, 2 of 5 LGG patients
      were stable over 18 months, with 1 stable for 6 months. Overall 5 of 10 LGG
      patients have responded. On the basis of low toxicity and the promising LGG
      response, poly-ICLC may be effective for childhood LGG, and the results justify
      biomarker studies for personalization of poly-ICLC as a single agent or adjuvant.

PMID- 24309610
TI  - Abnormal pulmonary function and associated risk factors in children and
      adolescents with sickle cell anemia.
AB  - Obstructive and restrictive pulmonary changes develop in children with sickle
      cell disease, but reports conflict as to the type of change that predominates. We
      prospectively performed spirometry, plethysmography, and lung diffusing capacity
      in 146 children aged 7 to 20 years with hemoglobin SS or Sbeta(0)-thalassemia.
      Nineteen percent of the patients had obstructive physiology as defined according
      to guidelines of the American Thoracic Society. In addition, 9% had restrictive
      physiology and 11% had abnormal but not categorized physiology. Increasing age,
      patient-reported or family-reported history of asthma or wheezing, and higher
      lactate dehydrogenase concentration were independent predictors of obstruction as
      reflected in lower forced expiratory volume in the first second/forced vital
      capacity. In conclusion, abnormal pulmonary function, most often obstructive, is
      common in children with hemoglobin SS and Sbeta(0)-thalassemia. Full pulmonary
      function testing should be performed in children with hemoglobin SS or Sbeta(0)
      thalassemia, especially with history of asthma or wheezing and accentuated
      elevations in hemolytic markers.

PMID- 24309611
TI  - What do parents want to know when considering autopsy for their child with
      cancer?
AB  - Research has suggested that autopsy in pediatrics is a valued way for parents to
      better understand and process their child's death, yet physicians often express
      hesitancy in discussing this topic with parents. To better assist clinicians with
      initiating discussion about this often sensitive topic, the current study
      examined bereaved parents' preferences about the timing and content of the
      autopsy discussion as well as reasons for considering autopsy. This study
      explored the views of 30 parents who lost a child to a variety of malignancies
      between 6 months and 6 years ago. Results showed that 36.7% of parents recalled
      having a discussion about autopsy, and the vast majority of those who did not
      recall a discussion (89.5%) would have considered an autopsy if it had been
      discussed. The majority of participants in this study indicated their preference
      to have the first conversation about autopsy when it becomes clear that cure is
      no longer possible. Findings suggest that educating parents about the clinical,
      emotional, and potential research benefits of autopsy and tissue procurement will
      ultimately help them make informed decisions and understand the importance of
      autopsy in medical progress. The future research and clinical implications of
      these findings are discussed. 

PMID- 24309612
TI  - Primary care physician perceptions of adult survivors of childhood cancer.
AB  - Increasing cure rates for childhood cancers have resulted in a population of
      adult childhood cancer survivors (CCS) that are at risk for late effects of
      cancer-directed therapy. Our objective was to identify facilitators and barriers
      to primary care physicians (PCPs) providing late effects screening and evaluate
      information tools PCPs perceive as useful. We analyzed surveys from 351
      practicing internal medicine and family practice physicians nationwide. A
      minority of PCPs perceived that their medical training was adequate to recognize
      late effects of chemotherapy (27.6%), cancer surgery (36.6%), and radiation
      therapy (38.1%). Most PCPs (93%) had never used Children's Oncology Group
      guidelines, but 86% would follow their recommendations. Most (84% to 86%) PCPs
      stated that they had never received a cancer treatment summary or survivorship
      care plan but (>90%) thought these documents would be useful. PCPs have a low
      level of awareness and receive inadequate training to recognize late effects.
      Overall, PCPs infrequently utilize guidelines, cancer treatment summaries, and
      survivorship care plans, although they perceive such tools as useful. We have
      identified gaps to address when providing care for CCS in routine general medical
      practice. 

PMID- 24309613
TI  - Bilateral parotid gland enlargement and palpable nephromegaly in infant acute
      lymphoblastic leukemia: case report and review of the literature.
AB  - Acute lymphoblastic leukemia (ALL) in infants below 1 year of age accounts for
      2.5% to 5% of childhood ALL. Most children with ALL present with fever, bruising,
      mucosal bleeding, bone pain, pallor, hepatosplenomegaly, and lymphadenopathy.
      Common sites of extramedullary involvement at diagnosis include liver, spleen,
      lymph nodes, brain, and testes. Nephromegaly has also been reported. We present a
      novel case of bilateral parotid enlargement along with bilateral palpable
      nephromegaly in a patient with newly diagnosed infant ALL. This unique
      presentation highlights the importance of considering ALL in the differential
      diagnosis of parotid enlargement especially when associated with abnormal blood
      counts. 

PMID- 24309614
TI  - Acute colchicine intoxication complicated with extramedullary hematopoiesis due
      to filgrastim in a child.
AB  - Colchicine is a widely used alkaloid extract in children and adults for standard
      therapy and prophylaxis for amyloid deposition in different rheumatologic
      disorders. Colchicine intoxication is a rare but severe complication. The aim of
      this study was to report the extramedullary hematopoiesis as a complication of
      filgrastim usage in a child with acute colchicine intoxication. Herein, we report
      a 3-year-old boy with colchicine intoxication associated with neutropenia,
      disseminated intravascular coagulation, liver injury, and rhabdomyolysis without
      hepatosplenomegaly. Filgrastim was started at the fourth day of administration
      for severe neutropenia with fever; 3 days after the start of filgrastim, the
      patient experienced hepatosplenomegaly with severe leukocytosis (51,110/mm) and
      myeloid precursors at peripheral blood smear. Bone marrow aspiration was normal;
      the clinical outcome of the child was eventful without any complication. The
      clinicians managing colchicine intoxications must be vigilant about the possible
      side effect of extramedullary hematopoiesis caused by filgrastim used for
      neutropenia in colchicine intoxication. 

PMID- 24309615
TI  - An interprofessional consensus of core competencies for prelicensure education in
      pain management: curriculum application for physical therapy.

PMID- 24309616
TI  - Enhanced therapeutic alliance modulates pain intensity and muscle pain
      sensitivity in patients with chronic low back pain: an experimental controlled
      study.
AB  - BACKGROUND: Physical therapy influences chronic pain by means of the specific
      ingredient of an intervention as well as contextual factors including the setting
      and therapeutic alliance (TA) between provider and patient. OBJECTIVE: The
      purpose of this study was to compare the effect of enhanced versus limited TA on
      pain intensity and muscle pain sensitivity in patients with chronic low back pain
      (CLBP) receiving either active or sham interferential current therapy (IFC).
      DESIGN: An experimental controlled study with repeated measures was conducted.
      Participants were randomly divided into 4 groups: (1) AL (n=30), which included
      the application of active IFC combined with a limited TA; (2) SL (n=29), which
      received sham IFC combined with a limited TA; (3) AE (n=29), which received
      active IFC combined with an enhanced TA; and (4) SE (n=29), which received sham
      IFC combined with an enhanced TA. METHODS: One hundred seventeen individuals with
      CLBP received a single session of active or sham IFC. Measurements included pain
      intensity as assessed with a numerical rating scale (PI-NRS) and muscle pain
      sensitivity as assessed via pressure pain threshold (PPT). RESULTS: Mean
      differences on the PI-NRS were 1.83 cm (95% CI=14.3-20.3), 1.03 cm (95% CI=6.6
      12.7), 3.13 cm (95% CI=27.2-33.3), and 2.22 cm (95% CI=18.9-25.0) for the AL, SL,
      AE, and SE groups, respectively. Mean differences on PPTs were 1.2 kg (95% CI=0.7
      1.6), 0.3 kg (95% CI=0.2-0.8), 2.0 kg (95% CI=1.6-2.5), and 1.7 kg (95% CI=1.3
      2.1), for the AL, SL, AE, and SE groups, respectively. LIMITATIONS: The study
      protocol aimed to test the immediate effect of the TA within a clinical
      laboratory setting. CONCLUSIONS: The context in which physical therapy
      interventions are offered has the potential to dramatically improve therapeutic
      effects. Enhanced TA combined with active IFC appears to lead to clinically
      meaningful improvements in outcomes when treating patients with CLBP.

PMID- 24309617
TI  - Are repeated single-limb heel raises and manual muscle testing associated with
      peak plantar-flexor force in people with inclusion body myositis?
AB  - BACKGROUND: Repeated heel raises have been proposed as a method of ankle plantar
      flexor strength testing that circumvents the limitations of manual muscle testing
      (MMT). OBJECTIVE: The study objective was to examine the relationships among
      ankle plantar-flexion isometric maximum voluntary contraction (MVC), repeated
      single-limb heel raises (SLHRs), and MMT in people with myositis. DESIGN: This
      was a cross-sectional study with a between-group design. The ability to complete
      1 SLHR determined group assignment (SLHR group, n=24; no-SLHR group, n=19).
      METHODS: Forty-three participants with myositis (13 women; median age=64.9 years)
      participated. Outcome measures included MVC, predicted MVC, Kendall MMT, and
      Daniels-Worthingham MMT. RESULTS: The Kendall MMT was unable to detect
      significant ankle plantar-flexor weakness established by quantitative methods and
      was unable to discriminate between participants who could and those who could not
      perform the SLHR task. Ankle plantar-flexion MVC was not associated with the
      number of heel-raise repetitions in the SLHR group (pseudo R(2)=.13). No
      significant relationship was observed between MVC values and MMT grades in the
      SLHR and no-SLHR groups. However, a moderate relationship between MVC values and
      MMT grades was evident in a combined-group analysis (rho=.50-.67). LIMITATIONS:
      The lower half of both MMT grading scales was not represented in the study
      despite the profound weakness of the participants. CONCLUSIONS: Both Kendall MMT
      and Daniels-Worthingham MMT had limited utility in the assessment of ankle
      plantar-flexor strength. Repeated SLHRs should not be used as a proxy measure of
      ankle plantar-flexion MVC in people with myositis.

PMID- 24309618
TI  - Residency education in every town: is it just so simple?

PMID- 24309619
TI  - Selection of patients for ambulatory lumbar discectomy: results from four US
      states.
AB  - BACKGROUND CONTEXT: There is a persistent trend for more outpatient lumbar
      discectomies in the United States. PURPOSE: To investigate the characteristics of
      the patients selected for ambulatory procedures. STUDY DESIGN: Retrospective
      cohort study. PATIENT SAMPLE: Forty-seven thousand one hundred twenty-five
      patients who underwent outpatient and 102,592 patients undergoing inpatient
      lumbar discectomies and were were registered in the State Ambulatory Surgery
      Database (SASD) and State Inpatient Database (SID), respectively, for New York,
      California, Florida, and North Carolina from 2005 to 2008. OUTCOME MEASURES: Rate
      of outpatient procedures, 30-day readmissions, and hospital charges. METHODS: We
      performed a retrospective cohort study involving patients who underwent
      outpatient and inpatient lumbar discectomies and were registered in SASD and SID,
      respectively, for New York, California, Florida, and North Carolina from 2005 to
      2008. Logistic regression models were used to demonstrate the association of
      socioeconomic factors with the odds of undergoing an outpatient procedure.
      RESULTS: Male gender (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03
      1.08), private insurance (OR, 1.93; 95% CI, 1.86-2.01), lower Charlson
      Comorbidity Index (OR, 4.04; 95% CI, 3.17-5.16), and higher volume hospitals (OR,
      1.06; 95% CI, 1.04-1.08) were significantly associated with outpatient
      procedures. Higher income (OR, 0.83; 95% CI, 0.81-0.85), older age (OR, 0.996;
      95% CI, 0.995-0.997), coverage by Medicaid (OR, 0.89; 95% CI, 0.83-0.96), African
      Americans (OR, 0.65; 95% CI, 0.60-0.70), and other minority races were associated
      with decreased odds of outpatient procedures. The rate of 30-day postoperative
      readmissions was higher among inpatients. Institutional charges were
      significantly lower for outpatient lumbar discectomies. The median charge for
      inpatient surgery was $24,273 as compared with $11,339 for the outpatient setting
      (p<.0001). CONCLUSIONS: Access to ambulatory lumbar discectomies appears to be
      more common for younger, white, male patients, with private insurance and less
      comorbidities, in the setting of higher volume hospitals. Further investigation
      is needed in the direction of mapping these disparities for appropriate resource
      utilization.

PMID- 24309620
TI  - Three component assemblies by orthogonal H-bonding and donor-acceptor charge
      transfer interaction.
AB  - Three component supramolecular assemblies from a mixture of an aromatic donor
      (D), acceptor (A) and external structure directing agent (ESDA) are achieved by
      orthogonal noncovalent interactions involving two different types of H-bonding
      and alternate D-A stacking. An ESDA containing amide or urea produces a charge
      transfer gel and sol, respectively, owing to their contrasting morphology. 

PMID- 24309621
TI  - Variations of dissection properties and mass fractions with thrombus age in human
      abdominal aortic aneurysms.
AB  - INTRODUCTION: Thrombus ages, defined as four relative age phases, are related to
      different compositions of the intraluminal thrombus (ILT) in the abdominal aortic
      aneurysm (AAA) (Tong et al., 2011b). Experimental studies indicate a correlation
      between the relative thrombus age and the strength of the thrombus-covered wall.
      METHODS: On 32 AAA samples we performed peeling tests with the aim to dissect the
      material (i) through the ILT thickness, (ii) within the individual ILT layers and
      (iii) within the aneurysm wall underneath the thrombus by using two extension
      rates (1mm/min, 1mm/s). Histological investigations and mass fraction analysis
      were performed to characterize the dissected morphology, to determine the
      relative thrombus age, and to quantify dry weight percentages of elastin and
      collagen in the AAA wall. RESULTS: A remarkably lower dissection energy was
      needed to dissect within the individual ILT layers and through the thicknesses of
      old thrombi. With increasing ILT age the dissection energy of the underlying
      intima-media composite continuously decreased and the anisotropic dissection
      properties for that composite vanished. The quantified dissection properties were
      rate dependent for both tissue types (ILT and wall). Histology showed that single
      fibrin fibers or smaller protein clots within the ILT generate smooth dissected
      surfaces during the peeling. There was a notable decrease in mass fraction of
      elastin within the thrombus-covered intima-media composite with ILT age, whereas
      no significant change was found for that of collagen. CONCLUSIONS: These findings
      suggest that intraluminal thrombus aging leads to a higher propensity of
      dissection for the ILT and the intima-media composite of the aneurysmal wall.

PMID- 24309623
TI  - Characterization of oligosorbents and application to the purification of
      ochratoxin A from wheat extracts.
AB  - The aim of this work was to optimize the preparation of an anti-ochratoxin A
      (OTA) oligosorbent (OS), a solid-phase extraction sorbent based on OTA aptamers
      covalently immobilized on sepharose. Different syntheses were carried out by
      modifying the side of the oligonucleotide chain bound to the sepharose, the
      length of the spacer arm between the aptamer and the sepharose and the amount of
      the aptamers introduced during the covalent grafting. Indeed, the capacity of OSs
      prepared using 3'- or 5'-amino-modified sequences with a C6 or a C12 was studied.
      In the best conditions, the concentration of aptamers sequence used during their
      grafting was increased and a capacity close to 40 nmol g(-1) of OS was reached.
      The potential of the resulting OSs was also studied in pure media. For this,
      their selectivity was checked by comparing them to a control sorbent prepared
      without immobilizing aptamers. Extraction recoveries close to 100% were obtained
      on all OSs, while no retention was observed on the control sorbent. OS does not
      demonstrate any cross-reactivity towards OTA metabolites, i.e., ochratoxin B and
      ochratoxin hydroquinone. The oligosorbent was finally applied to the clean-up of
      OTA from wheat sample extracts. Extraction recoveries were not affected by matrix
      interferences and the resulting chromatogram clearly highlights the selectivity
      of the sorbent that allows the removal of matrix components thus improving the
      reliability of the quantitation of OTA in real samples.

PMID- 24309622
TI  - Biomechanical model for evaluation of pediatric upper extremity joint dynamics
      during wheelchair mobility.
AB  - Pediatric manual wheelchair users (MWU) require high joint demands on their upper
      extremity (UE) during wheelchair mobility, leading them to be at risk of
      developing pain and pathology. Studies have examined UE biomechanics during
      wheelchair mobility in the adult population; however, current methods for
      evaluating UE joint dynamics of pediatric MWU are limited. An inverse dynamics
      model is proposed to characterize three-dimensional UE joint kinematics and
      kinetics during pediatric wheelchair mobility using a SmartWheel instrumented
      handrim system. The bilateral model comprises thorax, clavicle, scapula, upper
      arm, forearm, and hand segments and includes the sternoclavicular,
      acromioclavicular, glenohumeral, elbow and wrist joints. A single 17 year-old
      male with a C7 spinal cord injury (SCI) was evaluated while propelling his
      wheelchair across a 15-meter walkway. The subject exhibited wrist extension
      angles up to 60 degrees , large elbow ranges of motion and peak glenohumeral
      joint forces up to 10% body weight. Statistically significant asymmetry of the
      wrist, elbow, glenohumeral and acromioclavicular joints was detected by the
      model. As demonstrated, the custom bilateral UE pediatric model may provide
      considerable quantitative insight into UE joint dynamics to improve wheelchair
      prescription, training, rehabilitation and long-term care of children with
      orthopedic disabilities. Further research is warranted to evaluate pediatric
      wheelchair mobility in a larger population of children with SCI to investigate
      correlations to pain, function and transitional changes to adulthood. 

PMID- 24309624
TI  - Detection and quantification of benzodiazepines and Z-drugs in human whole blood,
      plasma, and serum samples as part of a comprehensive multi-analyte LC-MS/MS
      approach.
AB  - For the first time, a liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      multi-analyte approach based on a simple liquid-liquid extraction was developed
      and validated for fast target screening and quantification of benzodiazepines and
      Z-drugs in case of driving ability and crime responsibility in the three most
      important biosamples whole blood, plasma, and serum. Whole blood, plasma, and
      serum (500 MUL each) were extracted twice at pH 7.4 and at pH 10 with ether/ethyl
      acetate (1:1). Separation, detection, and quantification were performed using LC
      MS/MS with electrospray ionization in positive mode. The method was validated
      with respect to selectivity, ion suppression/enhancement of co-eluting analytes,
      matrix effects, recovery, process efficiency, accuracy and precision,
      stabilities, and limits of detection and quantification. For accuracy and
      precision, full calibration was performed with ranges from subtherapeutic to
      toxic concentrations. The presented LC-MS/MS approach as part of a universal
      multi-analyte concept for over 100 drugs was applicable for selective detection
      as well as accurate and precise quantification in whole blood, plasma, and serum.
      The approach was selective, sensitive, accurate, and precise for 16 of the 19
      tested drugs in whole blood, 18 in plasma, and 17 in serum. Only semiquantitative
      results could be obtained for zopiclone because of its instability in all tested
      biosamples. 

PMID- 24309625
TI  - In-house validation and factorial effect analysis of a liquid chromatography
      tandem mass spectrometry method for the determination of thyreostats in bovine
      blood plasma.
AB  - A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method allowing the rapid screening and confirmation of thyreostatic drugs in
      bovine blood plasma was developed and validated according to Commission Decision
      2002/657/EC, chapter 3.1.3 "alternative validation", by applying a matrix
      comprehensive in-house validation concept. Decision limit CCalpha, detection
      capability CCbeta, recovery, repeatability, within-laboratory reproducibility and
      the uncertainty of measurement were calculated. Furthermore, a factorial effect
      analysis was carried out to identify factors that have a significant influence on
      the method. Factors considered to be relevant for the method in routine analysis
      (e.g. operator, storage duration of the extracts before measurement, different
      cartridge lots and duration of sample preparation) were systematically varied on
      two levels during the validation study. Subsequently, the extent to which these
      factors influence the measurement results of the individual analytes was
      examined. 

PMID- 24309626
TI  - Recent advances in protein NMR spectroscopy and their implications in protein
      therapeutics research.
AB  - Nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography are the
      two main methods for protein three-dimensional structure determination at atomic
      resolution. According to the protein structures deposited in the Protein Data
      Bank, X-ray crystallography has become the dominant method for structure
      determination, particularly for large proteins and complexes. However, with the
      developments of isotope labeling, increase of magnetic field strength, common use
      of a cryogenic probe, and ingenious pulse sequence design, the applications of
      NMR spectroscopy have expanded in biological research, especially in
      characterizing protein dynamics, sparsely populated transient structures, weak
      protein interactions, and proteins in living cells at atomic resolution, which is
      difficult if not impossible by other biophysical methods. Although great advances
      have been made in protein NMR spectroscopy, its applications in protein
      therapeutics, which represents the fastest growing segment of the pharmaceutical
      industry, are still limited. Here we review the recent advances in the use of NMR
      spectroscopy in studies of large proteins or complexes, posttranslation
      modifications, weak interactions, and aggregation, and in-cell NMR spectroscopy.
      The potential applications of NMR spectroscopy in protein therapeutic assays are
      discussed. 

PMID- 24309628
TI  - [Interdisciplinary interaction for vascular diseases of the eye].

PMID- 24309627
TI  - Imaging of lipids in rat heart by MALDI-MS with silver nanoparticles.
AB  - Lipids are a major component of heart tissue and perform several important
      functions such as energy storage, signaling, and as building blocks of biological
      membranes. The heart lipidome is quite diverse consisting of glycerophospholipids
      such as phosphatidylcholines (PCs), phosphatidylethanolamines (PEs),
      phosphatidylinositols (PIs), phosphatidylglycerols (PGs), cardiolipins (CLs), and
      glycerolipids, mainly triacylglycerols (TAGs). In this study, mass spectrometry
      imaging (MSI) enabled by matrix implantation of ionized silver nanoparticles
      (AgNP) was used to map several classes of lipids in heart tissue. The use of AgNP
      matrix implantation was motivated by our previous work showing that implantation
      doses of only 10(14)/cm(2) of 2 nm gold nanoparticulates into the first 10 nm of
      the near surface of the tissue enabled detection of most brain lipids (including
      neutral lipid species such as cerebrosides) more efficiently than traditional
      organic MALDI matrices. Herein, a similar implantation of 500 eV AgNP(-) across
      the entire heart tissue section results in a quick, reproducible, solvent-free,
      uniform matrix concentration of 6 nm AgNP residing near the tissue surface. MALDI
      MSI analysis of either positive or negative ions produce high-quality images of
      several heart lipid species. In negative ion mode, 24 lipid species [16 PEs, 4
      PIs, 1 PG, 1 CL, 2 sphingomyelins (SMs)] were imaged. Positive ion images were
      also obtained from 29 lipid species (10 PCs, 5 PEs, 5 SMs, 9 TAGs) with the TAG
      species being heavily concentrated in vascular regions of the heart.

PMID- 24309629
TI  - [Long-term results after trabeculectomy with 5-fluorouracil].
AB  - PURPOSE: Trabeculectomy is among the first choice surgical treatments for
      glaucoma. Antimetabolites, especially mitomycin C, have improved the success
      rate. The aim of this study is to present the results of trabeculectomy with 5
      fluorouracil (5-FU). METHODS: A total of 71 consecutive trabeculectomies with 5
      FU for decompensated glaucoma with at least 1 year follow-up data were
      retrospectively evaluated. The absolute (without therapy) and relative (with
      therapy) success rates for glaucoma medication were determined for intraocular
      pressure (IOP) levels of <= 21 mmHg, <= 18 mmHg, <= 15 mmHg and <= 12 mmHg
      respectively. Postoperative 5-FU administration rates, needling procedures and
      complications were recorded. RESULTS: Sufficient follow-up data were available
      for a total of 55 patients. The average IOP was preoperatively 29.6 +/- 7.3 mmHg
      (3 +/- 1.4 active ingredients, partly acetazolamide), after 6 months 13.2 +/- 4.1
      mmHg and after 1 year 13.7 +/- 4.3 mmHg. Complete success at 6 months
      postoperatively for the given pressure levels: were 92 %, 87 %, 79 % and 52% and
      at 1 year 87 %, 84 %, 51 % and 56%, respectively. Postoperative relative success
      for these pressure levels at 6 months were 96 %, 90 %, 81 % and 54% and at 1 year
      96 %, 93 %, 58 % and 58%, respectively. Administrations of 5-FU postoperatively
      were no intervention (n=30 patients), subconjunctival 5-FU administration (n=25)
      and needling procedures (n=6). A temporary hypotension with a shallow anterior
      chamber was seen in 6 patients, cataract development in 5 patients and 1 patient
      developed corneal decompensation (multiple previous operations before
      trabeculectomy). CONCLUSION: Trabeculectomy with intraoperative 5-FU
      administration showed very high success rates after 1 year. Serious complications
      were rarely seen. Intraoperative 5-FU administration can be considered as an
      alternative treatment to trabeculectomy with intraoperative use of mitomycin C.

PMID- 24309630
TI  - [Rare pigmented fundus tumor].

PMID- 24309631
TI  - [Treatment of severe recurrent symblepharopterygium: combined ipsilateral
      autologous limbus and homologous amniotic membrane transplantation].
AB  - BACKGROUND: This retrospective study reports on four patients with severe
      recurrent symblepharopterygium formation and extensive subconjunctival scarring
      who were treated with a novel surgical technique combining free limbal
      autografting and amniotic membrane transplantation. PATIENTS AND METHODS: The
      surgical technique included symblepharolysis, meticulous removal of
      subconjunctival scar tissue, ipsilateral free limbal autograft and homologous
      amniotic membrane transplantation. RESULTS: There were no intraoperative or
      postoperative adverse events and three patients had no manifestation of
      recurrence of pterygium, symblepharon or diplopia during a mean follow-up period
      of 172 +/- 18 weeks (39 +/- 4 months) postoperatively. Only one patient had
      persistent symblepharon and experienced a recurrence of pterygium approximately
      40 weeks (9 months) after surgery. CONCLUSION: The results suggest that
      ipsilateral autologous limbal and homologous amniotic membrane transplantation
      can be an effective therapeutic approach in the treatment of recurrent pterygium
      with symblepharon formation.

PMID- 24309632
TI  - Radiotherapy does not impair dentin adhesive properties in head and neck cancer
      patients.
AB  - OBJECTIVES: This study evaluated the influence of radiotherapy on the dentin bond
      strength of teeth extracted from patients who had undergone head and neck
      radiotherapy. MATERIALS AND METHODS: A total of 36 samples were divided into two
      experimental groups: group I (control group, n = 18) and group II (in vivo
      irradiated group, n = 18). Groups I and II were further separated into three
      subgroups (six specimens per subgroup), which were further assigned to the three
      adhesive system protocols employed: Single Bond 2 (SB) (3M ESPE), Easy Bond (EB)
      (3M ESPE) and Clearfil SE Bond (CSE) (Kuraray). The adhesive systems were applied
      to the prepared surface according to the manufacturers' instructions and restored
      using composite resin (Filtek Supreme, 3M ESPE). After 24 h in deionised water
      (37(o)C), teeth were horizontally and vertically cut to obtain beam specimens
      with a cross-section area of 0.8 +/- 1.0 mm(2). Specimens were tested in tension
      using a universal testing machine at a cross-speed of 0.5 mm/min. Fracture
      patterns were observed under SEM. Data was analysed by two-way analysis of
      variance (p <= 0.05). RESULTS: No statistically significant difference was found
      between the irradiated (R/SB = 44.66 +/- 10.12 MPa; R/EB = 41.48 +/- 12.71 MPa;
      and R/CSE = 46.01 +/- 6.98 MPa) and control group (C/SB = 39.12 +/- 9.51 MPa;
      C/EB = 42.40 +/- 6.66 MPa; and C/CSE = 36.58 +/- 7.06 MPa) for any of the
      adhesive systems. All groups presented a predominance of mixed fracture modes.
      CONCLUSION: Head and neck radiotherapy did not affect dentin bond strength for
      the adhesive materials tested in this study.

PMID- 24309633
TI  - Short exposure to a diet rich in both fat and sugar or sugar alone impairs place,
      but not object recognition memory in rats.
AB  - High energy diets have been shown to impair cognition however, the rapidity of
      these effects, and the dietary component/s responsible are currently unclear. We
      conducted two experiments in rats to examine the effects of short-term exposure
      to a diet rich in sugar and fat or rich in sugar on object (perirhinal-dependent)
      and place (hippocampal-dependent) recognition memory, and the role of
      inflammatory mediators in these responses. In Experiment 1, rats fed a cafeteria
      style diet containing chow supplemented with lard, cakes, biscuits, and a 10%
      sucrose solution performed worse on the place, but not the object recognition
      task, than chow fed control rats when tested after 5, 11, and 20 days. In
      Experiment 2, rats fed the cafeteria style diet either with or without sucrose
      and rats fed chow supplemented with sucrose also performed worse on the place,
      but not the object recognition task when tested after 5, 11, and 20 days. Rats
      fed the cafeteria diets consumed five times more energy than control rats and
      exhibited increased plasma leptin, insulin and triglyceride concentrations; these
      were not affected in the sucrose only rats. Rats exposed to sucrose exhibited
      both increased hippocampal inflammation (TNF-alpha and IL-1beta mRNA) and
      oxidative stress, as indicated by an upregulation of NRF1 mRNA compared to
      control rats. In contrast, these markers were not significantly elevated in rats
      that received the cafeteria diet without added sucrose. Hippocampal BDNF and
      neuritin mRNA were similar across all groups. These results show that relatively
      short exposures to diets rich in both fat and sugar or rich in sugar, impair
      hippocampal-dependent place recognition memory prior to the emergence of weight
      differences, and suggest a role for oxidative stress and neuroinflammation in
      this impairment.

PMID- 24309635
TI  - Graphene-analogue carbon nitride: novel exfoliation synthesis and its application
      in photocatalysis and photoelectrochemical selective detection of trace amount of
      Cu2+.
AB  - Graphene-analogue nanostructures defined as a new kind of promising materials
      with unique electronic, surface and optical properties have received much
      attention in the fields of catalysis, energy storage, sensing and electronic
      devices. Due to the distinctive structure characteristics of the graphene
      analogue materials, they brought novel and amazing properties. Herein, graphene
      analogue carbon nitride (GA-C3N4) was synthesized by high-yield, large-scale
      thermal exfoliation from the graphitic C3N4-based intercalation compound.
      Graphene-analogue carbon nitride exhibited 2D thin-layer structure with 6-9
      atomic thickness, a high specific surface area of 30.1 m(2) g(-1), increased
      photocurrent responses and improved electron transport ability, which could give
      rise to enhancing the photocatalytic activity and stability. The graphene
      analogue carbon nitride had a new features that could make it suitable as a
      sensor for Cu(2+) determination. So GA-C3N4 is a new but promising candidate for
      heavy metal ions (Cu(2+)) determination in water environment. The photocatalytic
      mechanism and photoelectrochemical selective sensing of Cu(2+) were also
      discussed.

PMID- 24309634
TI  - Sickness behaviour after lipopolysaccharide treatment in ghrelin deficient mice.
AB  - Ghrelin is an orexigenic hormone produced mainly by the gastrointestinal system
      and the brain. Much evidence also indicates a role for ghrelin in sleep and
      thermoregulation. Further, ghrelin was recently implicated in immune system
      modulation. Administration of bacterial lipopolysaccharide (LPS) induces fever,
      anorexia, and increased non-rapid-eye movement sleep (NREMS) and these actions
      are mediated primarily by proinflammatory cytokines. Ghrelin reduces LPS-induced
      fever, suppresses circulating levels of proinflammatory cytokines and reduces the
      severity and mortality of various models of experimental endotoxemia. In the
      present study, we determined the role of intact ghrelin signaling in LPS-induced
      sleep, feeding, and thermoregulatory responses in mice. Sleep-wake activity was
      determined after intraperitoneal, dark onset administration of 0.4, 2 and 10 MUg
      LPS in preproghrelin knockout (KO) and wild-type (WT) mice. In addition, body
      temperature, motor activity and changes in 24-h food intake and body weight were
      measured. LPS induced dose-dependent increases in NREMS, and suppressed rapid-eye
      movement sleep, electroencephalographic slow-wave activity, motor activity, food
      intake and body weight in both Ppg KO and WT mice. Body temperature changes
      showed a biphasic pattern with a decrease during the dark period followed by an
      increase in the light phase. The effects of the low and middle doses of LPS were
      indistinguishable between the two genotypes. Administration of 10 MUg LPS,
      however, induced significantly larger changes in NREMS and wakefulness amounts,
      body temperature, food intake and body weight in the Ppg KO mice. These findings
      support a role for ghrelin as an endogenous modulator of inflammatory responses
      and a central component of arousal and feeding circuits.

PMID- 24309636
TI  - Retraction blues.

PMID- 24309637
TI  - Drugs with dual-hormone action gain attention in diabetes field.

PMID- 24309639
TI  - Kinesin inhibitor marches toward first-in-class pivotal trial.

PMID- 24309640
TI  - Alzheimer's imaging agents struggle to find a market outside trials.

PMID- 24309641
TI  - Adolescent perceptions of drug advertising come under review.

PMID- 24309642
TI  - Straight talk with...BT Slingsby. Interviewed by Cassandra Willyard.
AB  - Japan boasts the second-largest pharmaceutical industry in the world. With its
      rich background in medical research, the country has turned its attention to
      diseases of the developing world with this year's launch of the Global Health
      Innovative Technology (GHIT) Fund--a new public-private partnership between five
      Japanese pharmaceutical companies, two government ministries and the Bill &
      Melinda Gates Foundation. In November, the Tokyo-based fund announced its first
      round of awards totaling $5.7 million. The six grants will go to partnerships
      aimed at developing new drugs and vaccines to fight malaria, tuberculosis and
      Chagas disease, a neglected disease endemic to Latin America. Leading the new
      $120 million, five-year initiative is BT Slingsby, a US-born scholar of the
      Japanese healthcare industry who most recently served as director of global
      partner solutions at Eisai, a Tokyo-based drugmaker. On a recent trip to New
      York, Slingsby, who serves as GHIT's executive director and CEO, met with
      Cassandra Willyard to discuss the new fund and how Japan can help drive
      development of medicines and vaccines for diseases of the developing world.

PMID- 24309644
TI  - Thanks for sharing.

PMID- 24309645
TI  - Advancing women in R&D will help accelerate medicine.

PMID- 24309651
TI  - It has to be the alphav: myofibroblast integrins activate latent TGF-beta1.

PMID- 24309652
TI  - Poker face no more: cancer recurrence reveals its hand.

PMID- 24309653
TI  - Metformin trims fats to restore insulin sensitivity.

PMID- 24309654
TI  - Reassessing the role of astrocytes in ammonia neurotoxicity.

PMID- 24309655
TI  - Another HIV vaccine failure: where to next?

PMID- 24309656
TI  - Harnessing the stem cell potential: the path to prevent mitochondrial disease.

PMID- 24309657
TI  - Harnessing the stem cell potential: a case for neural stem cell therapy.

PMID- 24309664
TI  - Measuring Care Continuity: A Comparison of Claims-based Methods.
AB  - BACKGROUND: Assessing care continuity is important in evaluating the impact of
      health care reform and changes to health care delivery. Multiple measures of care
      continuity have been developed for use with claims data. OBJECTIVE: This study
      examined whether alternative continuity measures provide distinct assessments of
      coordination within predefined episodes of care. RESEARCH DESIGN AND SUBJECTS:
      This was a retrospective cohort study using 2008-2009 claims files for a national
      5% sample of beneficiaries with congestive heart failure, chronic obstructive
      pulmonary disease, and diabetes mellitus. MEASURES: Correlations among 4 measures
      of care continuity-the Bice-Boxerman Continuity of Care Index, Herfindahl Index,
      usual provider of care, and Sequential Continuity of Care Index-were derived at
      the provider- and practice-levels. RESULTS: Across the 3 conditions, results on 4
      claims-based care coordination measures were highly correlated at the provider
      level (Pearson correlation coefficient r=0.87-0.98) and practice-level (r=0.75
      0.98). Correlation of the results was also high for the same measures between the
      provider- and practice-levels (r=0.65-0.92). CONCLUSIONS: Claims-based care
      continuity measures are all highly correlated with one another within episodes of
      care.

PMID- 24309665
TI  - Identifying the mechanisms for workplace burden of psychiatric illness.
AB  - BACKGROUND: Although previous research indicates that mental disorders detract
      from labor market outcomes, little is known about which psychiatric symptoms are
      most important. OBJECTIVE: The objective of this study was to identify the
      mechanisms, or most important symptoms, through which psychiatric disorders
      affect labor market outcomes. We focus on major depressive episode, panic attack,
      social phobia, and generalized anxiety disorder. Our approach builds on prior
      work in that we consider the effects of symptoms both among individuals meeting
      and among individuals not meeting the diagnostic criteria for mental disorders.
      RESEARCH DESIGN: Data were obtained from the National Comorbidity Survey
      Replication and the National Latino and Asian American Study. We used a
      structural equation model with latent indices for mental disorders, where the
      indices are generated from the model using multiple indicators (symptoms) and
      multiple causes of the disorders. MEASURES: The outcomes were current
      employment/labor force participation, weeks worked in last year, and number of
      work absences in the last month among employed individuals. RESULTS: We found
      that for major depressive episode, symptoms of insomnia/hypersomnia,
      indecisiveness, severe emotional distress, and fatigue are crucial for labor
      market outcomes. In the case of generalized anxiety disorder, the length of the
      episode, symptoms relating to difficulty controlling worry, and symptoms of
      worry/anxiety/nervousness causing significant emotional distress were most
      detrimental for work outcomes. Social phobia and panic attack were not associated
      with labor market outcomes. CONCLUSION: Our findings suggest that interventions
      targeting these particular symptoms may be most helpful in improving work
      functioning.

PMID- 24309663
TI  - Key roles of adjuvants in modern vaccines.
AB  - Vaccines containing novel adjuvant formulations are increasingly reaching
      advanced development and licensing stages, providing new tools to fill previously
      unmet clinical needs. However, many adjuvants fail during product development
      owing to factors such as manufacturability, stability, lack of effectiveness,
      unacceptable levels of tolerability or safety concerns. This Review outlines the
      potential benefits of adjuvants in current and future vaccines and describes the
      importance of formulation and mechanisms of action of adjuvants. Moreover, we
      emphasize safety considerations and other crucial aspects in the clinical
      development of effective adjuvants that will help facilitate effective next
      generation vaccines against devastating infectious diseases. 

PMID- 24309662
TI  - Development, maintenance and disruption of the blood-brain barrier.
AB  - The interface between the blood circulation and the neural tissue features unique
      characteristics that are encompassed by the term 'blood-brain barrier' (BBB). The
      main functions of this barrier, namely maintenance of brain homeostasis,
      regulation of influx and efflux transport, and protection from harm, are
      determined by its specialized multicellular structure. Every constituent cell
      type makes an indispensable contribution to the BBB's integrity. But if one
      member of the BBB fails, and as a result the barrier breaks down, there can be
      dramatic consequences and neuroinflammation and neurodegeneration can occur. In
      this Review, we highlight recently gained mechanistic insights into the
      development and maintenance of the BBB. We then discuss how BBB disruption can
      cause or contribute to neurological disease. Finally, we examine how this
      knowledge can be used to explore new possibilities for BBB repair. 

PMID- 24309666
TI  - Effects of continuity of care on medication duplication among the elderly.
AB  - BACKGROUND: The effects of continuity of care on health care outcomes are well
      documented. However, little is known about the effect of continuity at the
      physician or the site level on the process of care for patients with multiple
      chronic conditions (MCCs). OBJECTIVE: The objective of this study was to examine
      the effects of physician continuity versus site continuity on duplicated
      medications received by patients with and without MCCs. RESEARCH DESIGN AND
      SUBJECTS: This study utilized a longitudinal design with an 8-year follow-up from
      2004 to 2011 of patients aged 65 or older under a universal health insurance
      program in Taiwan (55,573 subjects and 389,011 subject-years). Generalized
      estimating equation models with propensity score method were conducted to assess
      the association between continuity and medication duplication. RESULTS: The rates
      of subjects receiving duplicated medications ranged from 40.38% to 43.50% with
      1.45-1.62 duplicated medications during the study period. The findings revealed
      that better continuity, either at the physician level or the site level, was
      significantly associated with fewer duplicated medications. This study also
      indicated that the physician continuity had a stronger effect on medication
      duplication than did site continuity. Furthermore, the magnitude of the
      protective effect of continuity against duplicated medications increased when the
      patients had more chronic conditions [physician continuity: the marginal effect
      ranged from -10.7% to -52.9% (all P<0.001); site continuity: the marginal effect
      ranged from -0.4% (P=0.063) to -31.4% (P<0.001)]. CONCLUSION: Improving either
      physician continuity or site continuity may result in fewer duplicated
      medications, particularly for patients with MCCs.

PMID- 24309667
TI  - The effect of macroeconomic conditions on the care decisions of the employed.
AB  - BACKGROUND: Medical care utilization has been found to be affected indirectly by
      changes in economic conditions through associated changes in employment or
      insurance status. However, if individuals interpret external macroeconomic
      conditions as employment risk, they may alter decisions to seek care even if they
      remain both employed and insured. OBJECTIVE: To examine the relationship between
      macroeconomic fluctuations and the medical care usage of Americans who are both
      employed and insured. RESEARCH DESIGN: Restricting the Medical Expenditure Panel
      Survey from 1995 to 2008 to respondents whose employment status and insurance
      status did not change, we employed a fixed-effect Poisson model to examine the
      association between state average annual unemployment rates and the utilization
      of 12 medical services. RESULTS: The average annual state unemployment rate was
      found to be a significant factor in hospital outpatient visits (P < 0.01) and
      emergency room visits (P < 0.01). A one percentage point increase in the
      unemployment rate was found to produce an additional 0.67 hospital outpatient
      visits and 0.14 emergency room visits. CONCLUSIONS: State unemployment rates were
      found statistically significantly associated with several of the medical services
      studied, suggesting macroeconomic conditions are an important factor in the
      medical decisions of employed and insured individuals. Thus, policy changes that
      increase access among the unemployed or uninsured may mitigate this employment
      risk effect and create incentives that potentially alter the utilization
      decisions among those currently both employed and insured.

PMID- 24309668
TI  - Response: effectiveness in primary care is paramount, but need not come at the
      expense of efficiency.
AB  - Effective primary care is vital to sustainable provision of primary care for the
      US population. However, efficiency and effectiveness go hand-in-hand. Effective
      care is that which enables a health system to optimize the performance of all
      care providers while eliminating wasteful practices. If high-quality patient care
      and strengthened patient-provider relationships are to occur outside of isolated
      pockets of innovation and spread to the populace as a whole, each primary care
      physician must work within a system that affords the tools, opportunity, and
      support needed to optimally manage a growing number of patients with mounting
      health care needs. The expectation that primary care physicians must come into
      direct contact with each and every patient, no matter the acuity or chief
      complaint, no longer meets the expectations of patients or those whom we would
      attract to enter the field of primary care. We can no longer repair the faults in
      our primary care workforce by simply increasing the number of providers working
      in exactly the same way primary care physicians have always worked. A modern
      workforce will require efficient practices to produce the most effective health
      care for the population. 

PMID- 24309669
TI  - A national study of challenges to electronic health record adoption and
      meaningful use.
AB  - BACKGROUND: Adoption and implementation of electronic health records (EHRs) has
      not been without challenges as it infuses technology into what has been a
      historically manual process of recording patient information. In an effort to
      identify these challenges, the Office of the National Coordinator for Health
      Information Technology leveraged the Regional Extension Center population of over
      140,000 providers to develop a structured way to track challenges to EHR adoption
      and Meaningful Use (MU). OBJECTIVES: This report summarizes challenges to EHR
      adoption and MU based on nationwide data supplied by 55 Regional Extension
      Centers reporting over 19,000 issues representing over 43,000 unique health care
      providers. Practices were grouped on the basis of their place in the lifecycle of
      EHR adoption and MU achievement. RESULTS: Provider engagement and administrative
      issues were among the more common issues reported across all cohorts. The most
      challenging MU measure was the clinical summaries measure, but MU Measure
      challenges varied by practice setting. CONCLUSIONS: EHR adoption and MU
      challenges are unique to practice setting and stage of the adoption process.

PMID- 24309670
TI  - Changes in thiazolidinedione use and outcomes following removal of a prior
      authorization policy: controlled time-series analysis.
AB  - OBJECTIVE: The aim of this study was to assess the impact of removing prior
      authorization restrictions on the use of thiazolidinediones (TZDs) and outcomes.
      METHODS: In a controlled interrupted time-series analysis, whereby new users of
      antidiabetic agents over 65 years of age in adjacent Canadian provinces with
      different TZD-related policies [Alberta (n = 16,653) and Saskatchewan (n = 6682)]
      were followed from January 2001 to December 2006. Prior authorization for TZDs
      was removed in Alberta (intervention province) in December 2003 (rosiglitazone)
      and February 2004 (pioglitazone); no policy changes occurred in Saskatchewan
      (control province). Adjusted differences in percent change between intervention
      and control provinces were used to estimate policy-attributable effects (PAE) on
      TZD use within 30 days and 1 year and patient outcomes (composite of all-cause
      mortality or hospitalization for acute coronary events or heart failure) within 1
      year. RESULTS: Mean age was 75 years, 51% were female, and 206,055 antidiabetic
      prescriptions were dispensed during follow-up. TZD use within 30 days among new
      users of antidiabetic agents increased almost >10% in Alberta compared with
      Saskatchewan controls immediately following the policy change: PAE = 9.4%, 95%
      confidence interval, 7.3%-11.6%. Other less expensive antidiabetic drug use
      decreased to exactly the same extent, suggesting TZD substitution. Compared with
      the controls, in Alberta there were no changes in the primary (clinical)
      composite outcome at 1 year (PAE = 0.31%, 95% confidence interval, -2.8% to
      +3.4%). CONCLUSIONS: The removal of a prior-authorization policy for TZDs was
      associated with an immediate increase in TZD use but did not impact patient
      outcomes. In this case, the policy removal shifted drug use to a more expensive
      drug with less certain clinical benefit.

PMID- 24309671
TI  - Covering the remaining uninsured children: almost half of uninsured children live
      in immigrant families.
AB  - OBJECTIVE: Previous authors have answered "how many children in immigrant
      families are uninsured"; we do not know the inverse: "how many uninsured children
      live in immigrant families." This paper will show the total contribution of
      having an immigrant parent to the uninsured rate for children in the United
      States. DATA SOURCE: Secondary data from the 2008-2010 American Community Survey.
      STUDY DESIGN: Descriptive analyses and a multinomial probit model illustrate the
      relationship between immigration history and insurance status. PRINCIPAL
      FINDINGS: In 2010, almost half (42%) of uninsured children lived in an immigrant
      family. State-level estimates range from a low of 4% in Maine to a high of 69% in
      California. Two thirds (69%) of these uninsured children are citizens;
      furthermore, 39% are Medicaid eligible, 39% are not eligible for Medicaid, and
      eligibility is unknown for the 21% that are low-income, noncitizens. CONCLUSIONS:
      In 2000, a third of all uninsured children lived in immigrant families. In 2010,
      42% of all uninsured children lived in immigrant families. Initiatives to expand
      coverage or increase Medicaid and CHIP uptake will require decision makers to
      develop new policy and outreach approaches to enroll these children so they do
      not fall further behind.

PMID- 24309672
TI  - Response to letter to the editor regarding the paper "potentially avoidable
      hospitalization for elderly long-stay residents in nursing homes".

PMID- 24309673
TI  - Do we really need more physicians? Responses to predicted primary care physician
      shortages.
AB  - Predicted primary care shortages have spurred action to increase the number of
      primary care physicians. However, simply increasing the number of primary care
      providers is not the only solution to resolving the imbalance between the supply
      of primary care physicians and the demand for primary care services. In this
      point-counterpoint, we highlight the limitations of existing primary care
      shortage predictions and discuss strategies to deliver primary care services
      without necessarily increasing the number of primary care physicians for a given
      population. Innovative solutions can be used to reduce or even eliminate
      projected primary care shortages while changing the prevailing paradigm of
      primary care. 

PMID- 24309674
TI  - Effectiveness over efficiency: underestimating the primary care physician
      shortage.
AB  - Interest in improving health care outcomes requires increasing the effectiveness
      of primary care. Focus on effectiveness is leading many innovative health systems
      to shrink primary care patient panels to strengthen relationships, and to enhance
      primary care teams to increase comprehensiveness. Such strategies would make
      primary care shortages worse than predicted, and are compounded by substantial
      declines in clinicians of all types choosing primary care careers. Severe primary
      care shortages beg for efficiency, but emphasizing efficiency at the expense of
      effectiveness threatens achieving the Triple Aim for health care. We cannot avoid
      the hard work of repairing our clinician training pipeline for primary care. 

PMID- 24309675
TI  - Distinguishing Selection Bias and Confounding Bias in Comparative Effectiveness
      Research.
AB  - Comparative effectiveness research (CER) aims to provide patients and physicians
      with evidence-based guidance on treatment decisions. As researchers conduct CER
      they face myriad challenges. Although inadequate control of confounding is the
      most-often cited source of potential bias, selection bias that arises when
      patients are differentially excluded from analyses is a distinct phenomenon with
      distinct consequences: confounding bias compromises internal validity, whereas
      selection bias compromises external validity. Despite this distinction, however,
      the label "treatment-selection bias" is being used in the CER literature to
      denote the phenomenon of confounding bias. Motivated by an ongoing study of
      treatment choice for depression on weight change over time, this paper formally
      distinguishes selection and confounding bias in CER. By formally distinguishing
      selection and confounding bias, this paper clarifies important scientific,
      design, and analysis issues relevant to ensuring validity. First is that the 2
      types of biases may arise simultaneously in any given study; even if confounding
      bias is completely controlled, a study may nevertheless suffer from selection
      bias so that the results are not generalizable to the patient population of
      interest. Second is that the statistical methods used to mitigate the 2 biases
      are themselves distinct; methods developed to control one type of bias should not
      be expected to address the other. Finally, the control of selection and
      confounding bias will often require distinct covariate information. Consequently,
      as researchers plan future studies of comparative effectiveness, care must be
      taken to ensure that all data elements relevant to both confounding and selection
      bias are collected. 

PMID- 24309676
TI  - Chiral metal nanoparticle-catalyzed asymmetric C-C bond formation reactions.
AB  - Chiral ligand-modified metal nanoparticles possess an attractive potential for
      application in asymmetric synthesis. This article focuses on chiral-nanoparticle
      catalyzed asymmetric C-C bond formation reactions and discusses the nature of the
      active species. 

PMID- 24309678
TI  - Facilitated Li+ ion transfer across the water/1,2-dichloroethane interface by the
      solvation effect.
AB  - We demonstrate that the solvation effect can be the driving force for ion
      transfer across the water/1,2-dichloroethane interface. Voltammetric behaviours
      of facilitated Li(+) ion transfer by the solvents of lithium-based batteries are
      investigated, which is valuable for the dual-electrolyte Li-air batteries, but
      also for the ion detection, separation and extraction. 

PMID- 24309679
TI  - Randomly Distributed Delayed Communication and Coherent Swarm Patterns.
AB  - Previously we showed how delay communication between globally coupled self
      propelled agents causes new spatio-temporal patterns to arise when the delay
      coupling is fixed among all agents [1]. In this paper, we show how discrete,
      randomly distributed delays affect the dynamical patterns. In particular, we
      investigate how the standard deviation of the time delay distribution affects the
      stability of the different patterns as well as the switching probability between
      coherent states.

PMID- 24309682
TI  - In these pages ....

PMID- 24309680
TI  - Evolution of plant eukaryotic initiation factor 4E (eIF4E) and potyvirus genome
      linked protein (VPg): a game of mirrors impacting resistance spectrum and
      durability.
AB  - Polymorphism in the plant eukaryotic translation initiation factor 4E (eIF4E) and
      potyvirus genome-linked protein (VPg) determine, in many cases, the outcome of
      the confrontation between these two organisms: compatibility (i.e. infection of
      the plant by the virus) or incompatibility (i.e. resistance of the plant to the
      virus). The two interacting proteins eIF4E and VPg show strikingly similar
      evolution patterns. Most codon positions in their coding sequences are highly
      constrained for nonsynonymous substitutions but a small number shows evidence for
      positive selection. Several of these latter positions were shown to be
      functionally important, conferring resistance to the host or pathogenicity to the
      virus. Determining the mutational pathways involved in pepper eIF4E
      diversification revealed a link between an increase of the pepper resistance
      spectrum towards a panel of potyvirus species and an increase of durability of
      the resistance towards Potato virus Y. This relationship questions the interest
      of using more generally the spectrum of action of a plant resistance gene as a
      predictor of its durability potential. 

PMID- 24309683
TI  - Freud, Ferenczi, and Rosmersholm: incestuous triangles and analytic thirds.
AB  - Utilizing a field theory of unconscious communication, and in particular the
      concept of the analytic third, this paper situates Freud's interpretation of
      Ibsen's 1886 Rosmersholm, presented in the section of his essay "Some Character
      Types Met with in Psycho-Analytic Work" (1916) entitled "Those Wrecked by
      Success," in the context of his relationship with Ferenczi. Both in his
      interpretation of Rosmersholm and in his earlier papers on the psychology of
      love, it is argued, Freud may be seen to commenting both on Ferenczi's incestuous
      love triangle with Gizella and Elma Palos and on his equally incestuous triangle
      with Martha and Minna Bernays. In a postscript, the challenge offered by Groddeck
      to Freud's oedipal reading of Rosmersholm is assessed. 

PMID- 24309684
TI  - "Uterus loquitur": trauma and the human organism in Ferenczi's "physiology of
      pleasure".
AB  - The paper reconstructs Ferenczi's unique and largely neglected physiology of
      pleasure. It highlights the prominent place of the libido in Ferenczi's writings,
      the transition from the physiology of use to the physiology of pleasure and the
      role of trauma in Ferenczi's work with a special emphasis on the beauty and
      plasticity of the body, the relations between its organs as well as the adaptive
      potential, the Orphic powers, and the natural vigor of the human organism.
      Ferenczi's theoretical assumptions and his powerful images of the human organism
      are examined in the light of Goethe's, Schopenhauer's, and Nietzsche's
      philosophies. 

PMID- 24309677
TI  - Pharmacologic inhibition of vacuolar H+ ATPase reduces physiologic and oncogenic
      Notch signaling.
AB  - Notch signaling in prominently involved in growth regulation in metazoan tissues.
      Because of this, Notch is often upregulated in cancer and current efforts point
      to developing drugs that block its activation. Notch receptor endocytosis towards
      acidic compartments is a recently appreciated determinant of signaling
      activation. Vacuolar H(+) ATPase (V-ATPase) is responsible for acidification of
      endocytic organelles and mutants in V-ATPase subunit encoding genes in model
      organisms have been recently shown to display loss of Notch signaling. Here, we
      show that administration of BafilomycinA1 (BafA1), a highly specific V-ATPase
      inhibitor decreases Notch signaling during Drosophila and Zebrafish development,
      and in human cells in culture. In normal breast cells, we find that BafA1
      treatment leads to accumulation of Notch in the endo-lysosomal system, and
      reduces its processing and signaling activity. In Notch-addicted breast cancer
      cells, BafA1 treatment reduces growth in cells expressing membrane tethered forms
      of Notch, while sparing cells expressing cytoplasmic forms. In contrast, we find
      that V-ATPase inhibition reduces growth of leukemia cells, without affecting
      Notch activatory cleavage. However, consistent with the emerging roles of V
      ATPase in controlling multiple signaling pathways, in these cells Akt activation
      is reduced, as it is also the case in BafA1-treated breast cancer cells. Our data
      support V-ATPase inhibition as a novel therapeutic approach to counteract tumor
      growth via signaling pathways regulated at the endo-lysosomal level. 

PMID- 24309685
TI  - Infantile trauma, therapeutic impasses and recovery.
AB  - Throughout his writings Ferenczi examines the role of the mother-infant
      relationship in healthy development as well as the difficulties that occur when
      that relationship is problematic. This paper using Ferenczi and Bion as
      theoretical background explores the clinical development of impasse in the
      treatment of hard to reach patients. These patients present special difficulty
      for analysis because they are not self reflective although they can be addicted
      to "processing," which is in lieu of emotional connection. Impasse occurs when
      the analyst does not detect the mimicry involved in processing. The paper offers
      the idea of recovery, rather than repair, in that such patients have "gone
      missing" in infancy. Recovery of lost potential can be found in relationship with
      the analyst and with significant others. 

PMID- 24309686
TI  - "So it really does exist-the sea-Serpent we've never believed in!" Ferenczi's
      influence on Freud revisited.
AB  - In the last phase of his work, Ferenczi created a new language for trauma, based
      on the fragmentation of mental life. In the paper on "The principles of
      relaxation and neocatharsis," Ferenczi reformulated the goal of analysis by
      proposing that "no analysis can be regarded ... as complete unless we have
      succeed in penetrating the traumatic material", where the "traumatic material"
      was not to be sought in the neurotic reactions and adaptive solutions of the ego
      but in more primitive reactions, such as the psychotic turning away from reality,
      splitting, and fragmentation. This was exactly the material that Freud
      assimilated in the essay "A disturbance of memory on the Acropolis", after the
      death of Ferenczi. Freud visited Athens in 1904, and the walk up to the Parthenon
      represented the successful coronation of his self-analysis. Actually, the
      hallucination turned out to be so uncanny that he never again visited Athens. In
      a letter to Fliess, written shortly before the meeting in Nuremberg, on January
      24, 1897, Freud reported on a case history turning on a "scene about the
      circumcision of a girl," who later was convincingly identified by Schur as Emma
      Eckstein. Did Freud have the germinal idea that Emma Eckstein's hallucination of
      the penis contained the wish to overcome her trauma and the hope to have a
      restored genital? Is this the holy visitation, which haunted him on the
      Acropolis? Why did he give up the profound insight that the dreams of gigantic
      snakes had a traumatic origin? 

PMID- 24309687
TI  - Girl who wrote to primo levi. The "foreign body" speaks.
AB  - Through the exposition of a clinical case, the author explores how a sexually
      abused woman can set up strategies for psychic survival to the feeling of
      catastrophe and how she can attempt to communicate and share it. The clinical
      case connects childhood sexual abuse trauma and the trauma of surviving
      concentration camps. The paper refers to two main achievements of Ferenczi's
      research: (1) the consequences of the traumatic experience and of the disavowal
      of it, such as dissociation, fragmentation, psychic agony; and (2) the focus on
      countertransference as emotional sharing and as receptiveness to the deep,
      unconscious and unspeakable communications, which can transfer to the
      psychoanalyst through somatic ways. 

PMID- 24309688
TI  - Flirting with death: the role of father in containment of sexually perverse
      behavior.
AB  - The author demonstrates, through clinical case illustration, how sexual
      perversion is linked to traumatic early separation-individuation processes. The
      illusion of fusion with a seductive and gratifying mother-introject led a young
      man into the risky business of unprotected gay sex with strangers. The pleasure
      seeking child and enabling mother narrative was played out in the
      transference/counter-transference relationship threatening to pervert the
      analysis. Authoritative limit setting re-introduced a potent, previously
      castrated, father figure into the patient's inner world and gave the patient
      impetus to separate from the undifferentiated mix-up between mother and child,
      resulting in containment of dangerous sexual behaviors. 

PMID- 24309695
TI  - Isolation of abscisic acid-resistant variants from tobacco cell cultures : I.
      Physiological bases for selection.
AB  - The goal of this work was to begin a genetic study of the molecular mode of
      action of abscisic acid (ABA), by isolating variant cultured cells resistant to
      the hormone, or to a factor which induces ABA synthesis, namely water stress.
      Cell cultures of Nicotiana tabacum L. cv. Wisconsin 38 and N. silvestris Speg.
      and Comes were chosen as the experimental materials. Studies of the effects of
      the two stresses on the growth of the cultures demonstrated that ABA or water
      stress imposed by mannitol could completely inhibit growth. These effects arose
      in both cases from a constant reduction of the growth rate of the cells
      throughout the culture period. Mannitol also induced an increase in ABA content
      of the cells and media of suspension cultures, although not to the concentrations
      required to achieve the same degree of growth inhibition when the hormone was
      applied exogenously. 

PMID- 24309696
TI  - Isolation of abscisic acid-resistant variants from tobacco cell cultures : II.
      Selection and characterization of variants.
AB  - Variant clones were isolated from Nicotiana silvestris Speg. et Comes cell
      cultures at low frequencies following severe abscisic-acid (ABA) or mannitol
      induced water-stress treatments of plated cells. N. tabacum L. variants were not
      recovered. Variants from the ABA selection experiments exhibited a 10-fold
      increase in resistance to the hormone. This trait was stable in non-selective
      conditions for as long as was tested (200 days), but did not alter the response
      of the cells to water stress. Cell lines from the waterstress selection were not
      more resistant to mannitol than the parent line, and had a wide range of response
      to ABA. 

PMID- 24309697
TI  - Rearrangement of enzyme patterns in maize callus and suspension cultures : Is it
      relevant to the changes in the growing cells of the intact plant?
AB  - The development of enzyme patterns was followed in the course of: (a) the
      irreversible cell differentiation via division and expansion to maturity in the
      root tip and coleoptile of the intact seedlings, (b) the irreversible cell
      dedifferentation associated with induction and establishment of callus from the
      growing internodes, and (c) the growth cycle (proliferation?stationary phase) in
      callus and cell-suspension cultures of maize (Zea mays L.). By measuring the
      activities of glycolytic, mitochondrial, microbody and hydrolytic enzymes cells
      proliferating in vivo and in vitro could be compared and changes related to
      cessation or resumption of cell division could be studied.Proliferating cells of
      callus and suspension cultures maintained by serial culture did not differ from
      those of the root meristem and coleoptile in the specific activities of
      hexokinase, phosphoglycerate kinase and phosphopyruvate hydratase. Proliferation
      in vitro resulted in an enormous increase in the ratio g glutamate
      dehydrogenase/cytochrome-oxidase activity and in the level of acid-phosphatase
      activity, with concomitant drop in galactosidase and xylosidase activity. A 3-5
      fold increase of alcohol-dehydrogenase, lactate-dehydrogenase and catalase
      activities was characteristic of dividing callus cells, while a ca. 100-fold
      increase in the fructofuranosidase-to-glucosidase activity ratio marked cell
      proliferation in suspension-cultured cells.Changing enzyme activities after
      cessation of proliferation were quite similar in root tips and coleoptiles,
      except those of alcohol dehydrogenase and catalase. The enzyme rearrangement
      during callus establishment and in the growth cycle of callus cultures was in
      most cases comparable to that in the intact tissues, while the changes from the
      dividing to the non-dividing cells in suspension cultures, in contrast, differed
      widely from those in the intact tissues and callus. Galactosidase and xylosidase
      were the only activities that showed a similar trend of changes in all the
      investigated, intact and in-vitro-grown cells.Thus, judged by the pattern of
      enzyme development, the cell suspension appears to be a unique system, virtually
      unrelated to the growing cells of the intact tissues. It is also very difficult
      to draw a definite distinction between the metabolic consequences of cell growth
      and enzyme modulations in cell suspensions as the cells adapt their metabolism to
      the environmental changes in liquid medium. 

PMID- 24309698
TI  - Evidence for proteins specific for vascular elements in intact and cultured
      tissues and cells of maize.
AB  - A group of antigenically distinct proteins characteristic for the tissue complex
      of the vascular cylinders was found in maize (Zea mays L.) seedlings using an
      immunofiltration technique. Specific stelar antigens present in the fully
      developed stele (vascular cylinder) of the primary root were also found in steles
      extracted from adventitious roots and from the mesocotyl but were absent, within
      the limits of sensitivity of the immunodiffusion tests employed, in root cortex
      and epidermis. Some of the stelar antigens were also evident in the meristem of
      the primary root and were present in traces in the scutellum, the mesocotyl node,
      and the primary leaves plus coleoptile. The specific stelar antigens could be
      traced in 13- and 15-day-old developing embryos and were definitely expressed by
      the 21 st day after pollination. Several stelar-specific antigens were found in
      embryo-derived callus tissues and in stem-derived cells maintained in serial
      suspension culture. Higher resolution of the stelar antigens by a modified
      technique of crossed immunoelectrophoresis was used to demonstrate several minor
      stelar antigens that were presumably characteristic exclusively of the completely
      differentiated stele. This technique along with sequential immunoprecipitation of
      labelled proteins provided a semiquantitative estimate of the specific stelar
      antigens in the meristem and the stele of the primary root, and in suspension
      cultured cells which were devoid of noticeable signs of vascular differentiation.

PMID- 24309699
TI  - Different endogenous cytokinins between male and female Mercurialis annua L.
AB  - The endogenous pool of cytokinin metabolites during sexual differentiation of
      Mercurialis annua L. was studied with a computerized gas-chromatography-mass
      spectrometry system. Certain metabolites were common to both sexes: ribosides
      (isopentenyl-adenosine, ribosylzeatin) and the nucleotide of I6-Ade. Zeatin could
      be detected only in females while its nucleotide was present in males. The
      results were obtained with differentiating apices and whole plants. The high Z
      concentration and the low level of its nucleotide are related to the absence of
      two dominant complementary genes, determining maleness. Study of the regulation
      of cytokinin metabolism now seems possible. 

PMID- 24309700
TI  - Symplasmic and apoplasmic radial ion transport in plant roots : Cortical
      plasmalemmas lose absorption capacity during differentiation.
AB  - The kinetics and localization of Rb(+) uptake by barley roots were studied as
      function of the water potential of the medium. At potentials causing plasmolysis,
      uptake is reduced and becomes restricted to the outer surface of the root. The
      conclusion is that, at least for Rb(+) in the range of low external
      concentrations (<1 mM), the mature root cortex has little if any primary
      absorption(1) capacity. Therefore, the apoplasmic pathway is of little or no
      significance for radial transport, which occurs by primary absorption at the
      epidermis and - perhaps - hypodermis followed by symplasmis transport to and
      through the cortex. Young cortex cells possess a primary absorption capacity
      comparable to that of the epidermis, but this feature is (largely) lost during
      differentiation. 

PMID- 24309701
TI  - Ultrastructural and physiological differences between buds and mature flowers of
      Petunia hybrida prior to and following pollination.
AB  - The structural events accompanying the maturation of the pistil of Petunia
      hybrida have been studied in detail, together with the changes in the protein
      spectrum of the transmitting tissue that occur over this period. These events
      have been considered in terms of the acquisition of the self-incompatibility
      response, which occurs while the pistil is enclosed in the bud. Apart from
      several minor differences, the young pistils differ only from the mature in that
      their transmitting tissue cells fail to respond to pollination by undergoing
      characteristic ultrastructural changes. Data from electrofocusing indicates that
      several proteins, mobilised in the mature transmitting tissue some three hours
      after pollination, are absent from bud pistils. It is proposed that the
      pollination-stimulated release of certain polypeptides, believed to be involved
      in the self-incompatibility response, does not take place in young pistils. These
      observations are considered with reference to currently-accepted models of the
      operation of the self-incompatibility mechanism in Petunia. 

PMID- 24309702
TI  - Formation of protein storage bodies during embryogenesis in cotyledons of Sinapis
      alba L.
AB  - An electron microscopic investigation of fine structural changes in post
      meristematic cotyledon mesophyll cells during the period of storage protein
      accumulation (16-32 d after pollination) showed that the rough ER, the Golgi
      apparatus and the developing vacuome are intimately involved in the formation of
      storage protein bodies (aleurone bodies). At the onset of storage protein
      accumulation (16-18 d after pollination) storage protein-like material appears
      within Golgi vesicles and preformed vacuoles. At a later stage (24 d after
      pollination) similar material can also be detected within vesicles formed
      directly by the rough endoplasmic reticulum (ER). It is concluded that there are
      two routes for storage protein transport from its site of synthesis at the ER to
      its site of accumulation in the vacuome. The first route involves the
      participation of dictyosomes while the second route bypasses the Golgi apparatus.
      It appears that the normal pathways of membrane flow in the development of
      central vacuoles in post-meristematic cells are used to deposit the storage
      protein within the protein bodies. Thus, the protein body can be regarded as a
      transient stage in the process of vacuome development of these storage cells. 

PMID- 24309703
TI  - The B-ring hydroxylation pattern of intermediates of anthocyanin synthesis in
      pelargonidin-and cyanidin-producing lines of Matthiola incana.
AB  - In flowers of Matthiola incana, the B-ring hydroxylation pattern of anthocyanins
      is controlled by the locus b. Recessive genotypes produce pelargonidin and
      genotypes with wild-type alleles cyanidin as the aglycone. Supplementation
      experiments on acyanic flowers using extracts of pelargonidin-and cyanidin
      producing flowers, respectively, showed not only the presence of compounds with a
      precursor function for anthocyanin synthesis in the cyanic flowers but also
      differences in the B-ring hydroxylation pattern of these compounds.
      Chromatographic investigations proved that flavanones and dihydroflavonols occur
      in extracts of cyanic flowers. Naringenin, dihydrokaempferol, and their 7
      glucosides could be demonstrated in all flower extracts, but in extracts of
      cyanidin-producing flowers, dihydroquercetin and a further 3', 4'-hydroxylated
      dihydroflavonol, tentatively identified as dihydroquercetin 3-glycoside, were
      additionally found. In no case, however, could eriodictyol be detected. From
      these results and from the ready hydroxylation of dihydrokaempferol to
      dihydroquercetin in a white mutant line of Matthiola incana, it can be concluded
      that introduction of the 3'-hydroxyl group of anthocyanins is not achieved by
      specific incorporation of caffeic acid during synthesis of the flavonoid
      skeleton, but by hydroxylation at the dihydroflavonol stage. 

PMID- 24309704
TI  - Superoxide dismutase: A possible protective agent against sunscald in tomatoes
      (lycopersicon esculentum mill.).
AB  - Superoxide dismutase (SOD, EC 1.15.1.1) was concentrated from mature-green tomato
      fruits by gel chromatography. The enzyme was inhibited by cyanide but not by
      chloroform-ethanol, and appears to contain zinc and lesser amounts of copper. SOD
      activity levels were high in immature green fruits, declined to a minimum in the
      mature-green and breaker stages known to be most susceptible to sunscald damage,
      increased again until the fruits were pink, and finally decreased through the red
      ripe and overripe stages to the level of the mature-green fruit. When tolerance
      to sunscald damage was induced in mature-green fruits by controlled temperature
      treatment and samples of the fruits were challenged at various times during this
      process with a combined heat-and-light treatment known to cause sunscald, SOD
      activity was found to be inversely related to the susceptibility of the fruit to
      sunscald damage. It is suggested that superoxide is involved in sunscald injury
      to tomatoes and that tolerance is acquired through increases in SOD activity.
      Possibly SOD acts as a general protective agent against photodynamic damage to
      green tissues in plants that have become conditioned as the result of normal
      diurnal temperature fluctuations. 

PMID- 24309705
TI  - Purification of a non-chloroplastic alpha-glucan phosphorylase from spinach
      leaves.
AB  - The non-chloroplastic alpha-glucan phosphorylase (EC 2.4.1.1) from spinach leaves
      has been purified to homogeneity as revealed by dodecylsulfate gel
      electrophoresis. Both purification and separation from the chloroplastic
      phosphorylase were achieved by chromatography on Sepharose-bound dextrin. The
      chloroplastic phosphorylase did not bind to Sepharose-dextrin and was removed
      from the column by washing with buffer, as verified by polyacrylamide gel
      electrophoresis of the buffer eluate and by chromatography of a preparation from
      isolated intact chloroplasts. The non-chloroplastic phosphorylase did bind to a
      high extent to Sepharose-dextrin and could be eluted by a dextrin gradient. Based
      on dodecylsulfate gel electrophoresis and pyridoxal phosphate determination, a
      molecular weight of about 90,000 was found for the monomer. Molecular-weight
      determination by porosity density gradient electrophoresis and gel filtration on
      Sephadex G-200 suggested that the native enzyme is a dimer, as are other
      phosphorylases. 

PMID- 24309706
TI  - Correlation between loss of turgor and accumulation of abscisic acid in detached
      leaves.
AB  - Mature leaves of Phaseolus vulgaris L. (red kidney bean), Xanthium strumarium L.
      (cocklebur), and Gossypium hirsutum L. (cotton) were used to study accumulation
      of abscisic acid (ABA) during water stress. The water status of individual,
      detached leaves was monitored while the leaves slowly wilted, and samples were
      cut from the leaves as they lost water. The leaf sections were incubated at their
      respecitive water contents to allow ABA to build up or not. At least 8 h were
      required for a new steady-state level of ABA to be established. The samples from
      any one leaf covered a range of known water potentials (psi), osmotic pressures
      (pi), and turgor pressures (p). The pi and p values were calculated from
      "pressure-volume curves", using a pressure bomb to measure the water potentials.
      Decreasing water potential had little effect on ABA levels in leaves at high
      turgor. Sensitivity of the production of ABA to changes in psi progressively
      increased as turgor approached zero. At p=1 bar, ABA content averaged 4 times the
      level found in fully turgid samples. Below p=1 bar, ABA content increased sharply
      to as much as 40 times the level found in unstressed samples. ABA levels rose
      steeply at different water potentials for different leaves, according to the psi
      at which turgor became zero. These differences were caused by the different
      osmotic pressures of the leaves that were used; psi must cqual -pi for turgor to
      be zero. Leaves vary in pi, not only among species, but also between plants of
      one and the same species depending on the growing conditions. A difference of 6
      bars (calculated at psi=0) was found between the osmotic pressures of leaves from
      two groups of G. hirsutum plants; one group had previously experienced periodic
      water stress, and the other group had never been stressed. When individual leaves
      were subsequently wilted, the leaves from stress-conditioned plants required a
      lower water potential in order to accumulate ABA than did leaves from previously
      unstressed plants. On the basis of these results we suggest that turgor is the
      critical parameter of plant water relations which controls ABA production in
      water-stressed leaves. 

PMID- 24309707
TI  - Selection and characterization of a feedback-insensitive tissue culture of maize.
AB  - Tissue culture selection techniques were used to isolate a maize (Zea mays L.)
      variant D33, in which the aspartate family pathway was less sensitive to feedback
      inhibition by lysine. D33 was recovered by successively subculturing cultures
      originally derived from immature embryos on MS medium containing growth
      inhibitory levels of lysine+threonine. The ability of D33 to grow vigorously on
      lysine+ threonine medium was retained after growth for 12 months on nonselection
      medium. New cultures initiated from shoot tissues of plants regenerated from D33
      also were resistant to lysine+threonine inhibition. The Ki of aspartokinase for
      its feedback inhibitor, lysine, was about 9-fold higher in D33 than for the
      enzyme from unselected cultures. The free pools of lysine, threonine, isoleucine
      and methionine were increased 2-9-fold in D33 cultures. This was consistent with
      the observed change in feedback regulation of aspartokinase, the first enzyme
      common to the biosynthesis of these amino acids in the aspartate pathway. The
      accumulated evidence including the stability of resistance in the cultures, the
      resistance of cultures initiated from regenerated plants, the altered feedback
      regulation, and the increased free amino acids, indicates a mutational origin for
      these traits in line D33. 

PMID- 24309708
TI  - Opening of the hypocotyl hook in seedlings as influenced by light and adjacent
      tissues.
AB  - The influence of the cotyledons and apical bud and the root system on the light
      induced opening of the hypocotyl hook of etiolated seedlings of Gossypium
      hirsutum L., Phaseolus vulgaris L., Helianthus annuus L., Ipomoea alla L.,
      Ipomoea sp., Cucumis sativus L., Linum usitatissimum L., Hibiscus esculentus L.,
      and Raphanus sativus L. was studied. Light stimulated the opening of hypocotyl
      hook in all cases, but the cotyledons and roots had different effects in
      different plants. Generally, the presence of cotyledons and the remainder of the
      shoot apical to the hook inhibited light-mediated opening, but in Gossypium the
      organs stimulated light-mediated opening. Presence of roots either promoted
      opening, had no effect, or had an effect only when the cotyledons were present.
      In the dark the adjacent organs had a reduced effect over that shown in the
      light, but one cultivar of cotton, Acala SJ1, opened the hook in the dark without
      cotyledons as much as under any condition in the light. The variation between
      species in hook opening may related to the need of that process for a proper
      hormonal balance, as affected by light, which must be obtained from adjacent
      tissues. 

PMID- 24309709
TI  - Erratum.

PMID- 24309710
TI  - A large submucosal mass with prominent superficial vessels.

PMID- 24309711
TI  - Preparation and characterization of 4-isopropylcalix[4]arene-capped (3-(2-O-beta
      cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral
      stationary phase for high-performance liquid chromatography.
AB  - A new type of 4-isopropylcalix[4]arene-capped (3-(2-O-beta-cyclodextrin)-2
      hydroxypropoxy)propylsilyl-appended silica particles (IPC4CD-HPS) has been
      prepared by treatment of bromoacetate-substituted (3-(2-O-beta-cyclodextrin)-2
      hydroxypropoxy)propylsilyl-appended silica particles (BACD-HPS) with 4
      isopropylcalix[4]arene oxyanions in anhydrous N-methyl-2-pyrrolidone. The bonded
      silica IPC4CD-HPS has been successfully used as chiral stationary phase (CSP) in
      high-performance liquid chromatography (HPLC) for the first time. The synthetic
      stationary phase was characterized by means of elemental analysis and Fourier
      transform infrared spectroscopy. This new CSP has a chiral selector with two
      anchored functional moieties: 4-isopropylcalix[4]arene and beta-cyclodextrin. The
      chromatographic performance of IPC4CD-HPS was investigated by separation of
      positional isomers of several disubstituted benzenes and enantiomers of some
      chiral drug compounds under reversed-phase conditions. The results showed that
      IPC4CD-HPS had excellent selectivity for the separation of aromatic positional
      isomers and enantiomers of chiral compounds due to the cooperative functioning of
      the anchored 4-isopropylcalix[4]arenes and beta-cyclodextrins. 

PMID- 24309712
TI  - On-line sequential injection-capillary electrophoresis for near-real-time
      monitoring of extracellular lactate in cell culture flasks.
AB  - Cell culture has replaced many in vivo studies because of ethical and regulatory
      measures as well as the possibility of increased throughput. Analytical assays to
      determine (bio)chemical changes are often based on end-point measurements rather
      than on a series of sequential determinations. The purpose of this work is to
      develop an analytical system for monitoring cell culture based on sequential
      injection-capillary electrophoresis (SI-CE) with capacitively coupled contactless
      conductivity detection (C(4)D). The system was applied for monitoring lactate
      production, an important metabolic indicator, during mammalian cell culture.
      Using a background electrolyte consisting of 25mM
      tris(hydroxymethyl)aminomethane, 35mM cyclohexyl-2-aminoethanesulfonic acid with
      0.02% poly(ethyleneimine) (PEI) at pH 8.65 and a multilayer polymer coated
      capillary, lactate could be resolved from other compounds present in media with
      relative standard deviations 0.07% for intraday electrophoretic mobility and an
      analysis time of less than 10min. Using the human embryonic kidney cell line
      HEK293, lactate concentrations in the cell culture medium were measured every
      20min over 3 days, requiring only 8.73MUL of sample per run. Combining
      simplicity, portability, automation, high sample throughput, low limits of
      detection, low sample consumption and the ability to up- and outscale, this new
      methodology represents a promising technique for near real-time monitoring of
      chemical changes in diverse cell culture applications. 

PMID- 24309713
TI  - Editorial on "recent applications of on-line sample preconcentration techniques
      in capillary electrophoresis" by F. Kitagawa and K. Otsuka.

PMID- 24309714
TI  - Borate-aided anion exchange high-performance liquid chromatography of uridine
      diphosphate-sugars in brain, heart, adipose and liver tissues.
AB  - In this paper we describe a method optimized for the purification of uridine
      diphosphate (UDP)-sugars from liver, adipose tissue, brain, and heart, with
      highly reproducible up to 85% recoveries. Rapid tissue homogenization in cold
      ethanol, lipid removal by butanol extraction, and purification with a graphitized
      carbon column resulted in isolation of picomolar quantities of the UDP-sugars
      from 10 to 30mg of tissue. The UDP-sugars were baseline separated from each
      other, and from all major nucleotides using a CarboPac PA1 anion exchange column
      eluted with a gradient of acetate and borate buffers. The extraction and
      purification protocol produced samples with few unidentified peaks. UDP-N
      acetylglucosamine was a dominant UDP-sugar in all the rat tissues studied.
      However, brain and adipose tissue showed high UDP-glucose levels, equal to that
      of UDP-N-acetylglucosamine. The UDP-N-acetylglucosamine showed 2.3-2.7 times
      higher levels than UDP-N-acetylgalactosamine in all tissues, and about the same
      ratio was found between UDP-glucose and UDP-galactose in adipose tissue and brain
      (2.6 and 2.8, respectively). Interestingly, the UDP-glucose/UDP-galactose ratio
      was markedly lower in liver (1.1) and heart (1.7). The UDP-N
      acetylglucosamine/UDP-glucuronic acid ratio was also constant, between 9.7 and
      7.7, except in liver with the ratio as low as 1.8. The distinct UDP
      glucose/galactose ratio, and the abundance of UDP-glucuronic acid may reflect the
      specific role of liver in glycogen synthesis, and metabolism of hormones and
      xenobiotics, respectively, using these UDP-sugars as substrates. 

PMID- 24309715
TI  - Preparative two-dimensional liquid chromatography/mass spectrometry for the
      purification of complex pharmaceutical samples.
AB  - A new preparative two-dimensional liquid chromatography/mass spectrometry system
      (2D LC-LC/MS) has been designed and implemented to enhance capability and
      resolving power for the separation and purification of pharmaceutical samples.
      The system was constructed by modifications of a conventional preparative LC/MS
      instrument with the addition of a set of switching valves and a sample loop, as
      well as interfacing a custom software program with MassLynx. The system
      integrates two chromatographic separations from the first and second dimensions
      into a single automated run to perform the purification of a target compound from
      a complex mixture without intermediate steps of sample preparation. The
      chromatography in the first dimension, operated in the heart-cutting mode,
      separates the target compound from the impurities by mass-triggered fractionation
      based on its molecular weight. This purified fraction from the first dimension is
      stored in the sample loop, and then gets transferred to the second column by
      using at-column dilution. A control software program, coined Prep 2D LCMS, was
      designed to integrate with MassLynx to retrieve data acquisition status. All of
      the chromatographic hardware components used in this preparative 2D LC-LC/MS
      system are from the original open access preparative LC/MS system, which has high
      level of robustness and affords easy and user-friendly operation. The new system
      is very versatile and capable of collecting multiple fractions with different
      masses under various purification modes as configured in the methods, such as
      conventional one-dimensional (1D) purification and/or 2D purification. This new
      preparative 2D LC-LC/MS system is therefore the ideal tool for medicinal
      chemistry lab in drug discovery environment. 

PMID- 24309716
TI  - Preparation and characterisation of anion exchangers with dihydroxy-containing
      alkyl substitutes in the quaternary ammonium functional groups.
AB  - Novel poly(styrene-divinylbenzene) (PS-DVB) based anion exchangers having one and
      two (2,3-dihydroxypropyl) substitutes in the quaternary ammonium functional
      groups are prepared and characterised by ion chromatography (IC). The
      introduction of bulky and hydrophilic substitutes to the anion-exchange groups
      allows the elimination of non-ionic interactions between the polarisable anions
      and the aromatic rings from the matrix and the improvement of separation
      selectivity as compared with the traditional trimethylammonium (TMA)
      functionalised ion exchangers. The synthesis of the ion exchangers includes
      acylation of PS-DVB particles with acetic anhydride followed by reductive
      amination either with methylamine hydrochloride or dimethylamine and further
      alkylation with oxiranes under varied conditions. The ion exchange selectivity
      and separation efficiency of nine adsorbents having different structure of bonded
      groups, ion exchange capacity (9-98MUequiv.g(-1)) or particle size is studied for
      model mixture of inorganic anions (F(-), Cl(-), NO2(-), Br(-), NO3(-), HPO4(2-)
      and SO4(2-)) using carbonate and hydroxide eluents. The adsorbents with more
      hydrophilic substitutes provided superior columns efficiencies and better peak
      symmetry as compared with analogues having hydrophobic functional groups. The
      calculated values of column efficiencies for polarisable NO3(-) and HPO4(2-) are
      18,500 and 29,000N/m, respectively, for anion-exchanger, having N-methyl-N',N"-di
      (2,3-dihydroxypropyl)ammonium groups which is significantly higher than 1800 and
      12,000N/m obtained for these anions with anion exchanger bearing TMA functional
      groups. 

PMID- 24309717
TI  - Lung remodeling mechanisms in chronic lung diseases.
AB  - PURPOSE OF REVIEW: To summarize the new knowledge on tissue remodeling in the
      context of lung diseases. Tissue remodeling includes changes in cells:
      differentiation; response to growths factors, hormones, or environmental factors;
      and composition of the extracellular matrix. So, can one trigger cause them all
      or are they independently regulated? RECENT FINDINGS: New evidence from clinical
      and experimental studies strengthened the view that a susceptibility to
      remodeling can be initiated in early life and be re-activated by environmental
      triggers later in life. Many studies further support the idea that TGF-beta plays
      the central role in the pathogenesis of remodeling and fibrosis. However, the
      activation pathways and the end-effect of TGF-beta activation seems to be
      distinctive of disease and effecter cell specific patterns. The existing animal
      models do not properly reflect the human disease and thus have to be further
      improved. SUMMARY: The central role of TGF-beta on pathological mechanisms
      leading to remodeling and fibrosis has been further confirmed. However, the
      questions of why TGF-beta is activated as well as its disease and cell type
      specific mode of action remain to be answered. Based on clinical data redefining
      the term 'tissue remodeling' in a disease and cell type specific way should be
      considered.

PMID- 24309718
TI  - Innate lymphoid cells in asthma: when innate immunity comes in a Th2 flavor.
AB  - PURPOSE OF REVIEW: Asthma is typically considered as an immunologic Th2 cell
      mediated disease, a notion that is still inspiring many therapeutic strategies.
      In the past years, however, an innate immune cell type has been discovered in
      mice that resides in the mucosa and secretes the Th2 cytokines IL-13 and IL-5 in
      response to IL-33 and IL-25 released by a damaged epithelium. These cells [now
      named group 2 innate lymphoid cells (ILC2s)] are rare, systemically dispersed,
      long-lived, and exist in humans. Recent work shows that ILC2s are critical for
      the development of asthma and related phenotypes in mice. Their role in human
      asthma remains unknown. RECENT FINDINGS: This article reviews the most recent
      work that highlights ILC2s and the mechanisms underlying their critical role in
      experimental asthma. We also review the results of asthma therapeutic trials that
      targeted IL-13 and IL-5, the products of both Th2 cells and ILC2s. SUMMARY:
      Although the limited success of these trials is often quoted to dismiss the role
      of Th2 immunity as a whole, we propose that Th2 cytokines released by ILC2s may
      be critical for human asthma, but are not adequately neutralized because they are
      not readily accessible in peripheral tissues.

PMID- 24309719
TI  - Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout
      mice.
AB  - Steroid receptor coactivator-3 (SRC-3), a multifunctional transcriptional
      coactivator, plays an important role in regulation of cell apoptosis in
      chemoresistant cancer cells. However, its role in radiation-induced apoptosis in
      hematopoietic cells is still unclear. In this study, we used SRC-3 knockout (SRC
      3(-/-)) mice to assess the role of SRC-3 in radiation-induced hematopoietic
      injury in vivo. After a range of doses of irradiation, SRC-3(-/-) mice exhibited
      lower counts of peripheral blood cells and bone marrow (BM) mononuclear cells and
      excessive BM depression, which resulted in a significantly higher mortality
      compared with wildtype mice. Moreover, BM mononuclear cells obtained from SRC-3(
      /-) mice showed a remarkable increase in radiation-induced apoptosis.
      Collectively, our data demonstrate that SRC-3 plays a role in radiation-induced
      apoptosis of BM hematopoietic cells. Regulation of SRC-3 might influence the
      radiosensitivity of hematopoietic cells, which highlights a potential therapeutic
      target for radiation-induced hematopoietic injury. 

PMID- 24309720
TI  - Monte Carlo modeling in CT-based geometries: dosimetry for biological modeling
      experiments with particle beam radiation.
AB  - The space radiation environment imposes increased dangers of exposure to ionizing
      radiation, particularly during a solar particle event (SPE). These events consist
      primarily of low energy protons that produce a highly inhomogeneous dose
      distribution. Due to this inherent dose heterogeneity, experiments designed to
      investigate the radiobiological effects of SPE radiation present difficulties in
      evaluating and interpreting dose to sensitive organs. To address this challenge,
      we used the Geant4 Monte Carlo simulation framework to develop dosimetry software
      that uses computed tomography (CT) images and provides radiation transport
      simulations incorporating all relevant physical interaction processes. We found
      that this simulation accurately predicts measured data in phantoms and can be
      applied to model dose in radiobiological experiments with animal models exposed
      to charged particle (electron and proton) beams. This study clearly demonstrates
      the value of Monte Carlo radiation transport methods for two critically
      interrelated uses: (i) determining the overall dose distribution and dose levels
      to specific organ systems for animal experiments with SPE-like radiation, and
      (ii) interpreting the effect of random and systematic variations in experimental
      variables (e.g. animal movement during long exposures) on the dose distributions
      and consequent biological effects from SPE-like radiation exposure. The software
      developed and validated in this study represents a critically important new tool
      that allows integration of computational and biological modeling for evaluating
      the biological outcomes of exposures to inhomogeneous SPE-like radiation dose
      distributions, and has potential applications for other environmental and
      therapeutic exposure simulations. 

PMID- 24309721
TI  - Complete Genome of Acinetobacter baumannii Podophage Petty.
AB  - Acinetobacter baumannii is an emerging pathogen that was isolated from wounded
      soldiers in military treatment facilities in Iraq but has since become a problem
      in civilian hospitals. Here, we announce and describe the complete genome of the
      KMV-like A. baumannii podophage Petty. 

PMID- 24309722
TI  - Complete Genome of Acinetobacter baumannii N4-Like Podophage Presley.
AB  - Acinetobacter baumannii is an emerging multidrug-resistant nosocomial pathogen.
      Bacteriophages may be useful as an alternative method of treatment against this
      and other multidrug-resistant bacteria. Here, we present the complete genome
      sequence of A. baumannii phage Presley, an N4-like podophage. 

PMID- 24309723
TI  - Complete Genome of Bacillus thuringiensis Myophage BigBertha.
AB  - BigBertha is a myophage of Bacillus thuringiensis, a widely used biocontrol agent
      that is active against many insect pests of plants. Here, we present the complete
      annotated genome of BigBertha. The genome shares 85.9% sequence identity with
      Bacillus cereus phage B4. 

PMID- 24309724
TI  - Complete Genome of Bacillus pumilus Siphophage Blastoid.
AB  - Phage Blastoid is a siphophage that infects Bacillus pumilus. B. pumilus is
      widely used in agriculture but has recently been linked to cases of food
      poisoning. Here, we report the complete genome of Blastoid and discuss unique
      genomic characteristics. 

PMID- 24309725
TI  - Complete Genome of Bacillus pumilus Siphophage Glittering.
AB  - Bacillus pumilus is a Gram-positive bacterium widely used in agriculture both as
      an antifungal and as a growth-promoting symbiont. B. pumilus is rarely infectious
      but has recently been shown to infect humans. Here, we present the complete
      genome of B. pumilus phage Glittering, a potential biocontrol agent for B.
      pumilus. 

PMID- 24309726
TI  - Complete Genome of Bacillus subtilis Myophage Grass.
AB  - Bacillus subtilis is a ubiquitous Gram-positive model organism. Here, we describe
      the complete genome of B. subtilus myophage Grass. Aside from genes encoding core
      proteins pertinent to the life cycle of the phage, Grass has several interesting
      features, including an FtsK/SpoIIIE protein. 

PMID- 24309727
TI  - Complete Genome of Bacillus megaterium Podophage Pony.
AB  - Bacillus megaterium podophage Pony was isolated from a soil sample collected in
      College Station, TX. Here, we report the sequencing and annotation of the 39,844
      bp genome of phage Pony and describe the major features identified. 

PMID- 24309728
TI  - Complete Genome of Bacillus pumilus Siphophage Riggi.
AB  - Bacillus pumilus is primarily used in the agricultural industry to promote plant
      growth and provide resistance to bacterial and fungal plant diseases. It has
      recently, however, been shown to cause disease in humans. Here, we announce the
      complete genome of B. pumilus phage Riggi. 

PMID- 24309729
TI  - Complete Genome of Bacillus thuringiensis Myophage Spock.
AB  - Bacillus thuringiensis is a Gram-positive, sporulating soil microbe with valuable
      pesticide-producing properties. The study of bacteriophages of B. thuringiensis
      could provide new biotechnological tools for the use of this bacterium. Here, we
      present the complete annotated genome of Spock, a myophage of B. thuringiensis,
      and describe its features. 

PMID- 24309730
TI  - Complete Genome of Bacillus megaterium Siphophage Staley.
AB  - Siphophage Staley was isolated because of its ability to grow on Bacillus
      megaterium. Here we report the complete genome and annotation of phage Staley and
      describe core features. Among its interesting genes is one encoding an SleB
      germination protein. 

PMID- 24309731
TI  - Complete Genome of Clavibacter michiganensis subsp. sepedonicusis Siphophage
      CN1A.
AB  - Clavibacter michiganensis subsp. sepedonicusis is a Gram-positive actinomycete
      that is the causative agent of the potato disease ring rot. Here, we announce the
      complete genome sequence of the Clavibacter michiganensis subsp. sepedonicusis
      siphophage CN1A. CN1A is only the second fully sequenced Clavibacter
      michiganensis subsp. sepedonicusis phage reported to date. Core and unique
      features of its genome are described. 

PMID- 24309732
TI  - Complete Genome of Salmonella enterica Serovar Enteritidis Myophage Marshall.
AB  - Salmonella enterica serovar Enteritidis is a food-borne pathogen that causes
      salmonellosis in the United States. Bacteriophages are emerging as viable
      biocontrol agents against this pathogen. Here, we present the complete annotated
      genome sequence of Salmonella Enteritidis T4-like myophage Marshall, which has
      potential as a phage therapy agent. 

PMID- 24309733
TI  - Draft Genome Sequence of Plant Growth-Promoting Rhizobacterium Pantoea sp. Strain
      AS-PWVM4.
AB  - Nonpathogenic Pantoea spp. have been shown to confer biofertilizer and biocontrol
      activities, indicating their potential for increasing crop yield. Herein, we
      provide the high-quality genome sequence of Pantoea sp. strain AS-PWVM4, a Gram
      negative motile plant growth-promoting rhizobacterium isolated from a pomegranate
      plant. The 4.9-Mb genome contains genes related to plant growth promotion and the
      synthesis of siderophores. 

PMID- 24309734
TI  - Draft Genome Sequence of Veillonella parvula HSIVP1, Isolated from the Human
      Small Intestine.
AB  - Veillonella species are frequently encountered commensals in the human small
      intestine. Here, we report the draft genome sequence of the first cultured
      representative from this ecosystem, Veillonella parvula strain HSIVP1. The genome
      is predicted to encode all the necessary enzymes required for the pathway
      involved in the conversion of lactate to propanoate. 

PMID- 24309735
TI  - Draft Genome Sequence of Deinococcus xibeiensis R13, a New Carotenoid-Producing
      Strain.
AB  - Deinococcus xibeiensis strain R13, isolated from radiation-contaminated soils,
      synthesizes a unique ketocarotenoid, deinoxanthin. Here, we present a 3.49-Mb
      assembly of its genome sequence, which can help us find the key genes of the
      deinoxanthin biosynthesis pathways and modify genes obtaining a high yield of the
      new carotenoid. 

PMID- 24309736
TI  - Complete Genome Sequence of the Epidemic and Highly Virulent CTX-M-15-Producing
      H30-Rx Subclone of Escherichia coli ST131.
AB  - We report the complete genome sequence, including five complete plasmid
      sequences, of Escherichia coli ST131 isolate JJ1886. The isolate was obtained in
      2007 in the United States from a patient with fatal urosepsis and belongs to the
      virulent, CTX-M-15-producing H30-Rx sublineage. 

PMID- 24309737
TI  - Genome Sequences of Two Enterobacter pulveris Strains, 601/05T (=LMG 24057T =DSM
      19144T) and 1160/04 (=LMG 24058 =DSM 19146), Isolated from Fruit Powder.
AB  - We report the draft genome sequences of the Enterobacter pulveris strains
      601/05(T) (=LMG24057(T) =DSM19144(T)) and 1160/04 (=LMG24058 =DSM19146), isolated
      from fruit powder. The genome assemblies for the E. pulveris type strain,
      LMG24057, and strain LMG24058 have sizes of 4,708,624 and 4,811,103 bp and G+C
      contents of 56.6% and 56.5%, respectively. 

PMID- 24309738
TI  - Draft Genome Sequence of Shewanella decolorationis S12, a Dye-Degrading Bacterium
      Isolated from a Wastewater Treatment Plant.
AB  - Shewanella decolorationis is a valuable microorganism for degrading diverse
      synthetic textile dyes. Here, we present an annotated draft genome sequence of S.
      decolorationis S12, which contains 4,219 protein-coding genes and 86 structural
      RNAs. This information regarding the genetic basis of this bacterium can greatly
      advance our understanding of the physiology of this species. 

PMID- 24309739
TI  - Genome Sequence of Enterobacter turicensis Strain 610/05 (LMG 23731), Isolated
      from Fruit Powder.
AB  - We report the draft genome sequence of Enterobacter turicensis strain 610/05 (LMG
      23731), isolated from fruit powder. The draft genome has a size of 4,182,790 bp
      and a G+C% content of 58.0. 

PMID- 24309740
TI  - Complete Genome Sequence of Staphylococcus aureus Z172, a Vancomycin-Intermediate
      and Daptomycin-Nonsusceptible Methicillin-Resistant Strain Isolated in Taiwan.
AB  - We report the complete genome sequence of Z172, a representative strain of
      sequence type 239-staphylococcal cassette chromosome mec type III (ST239-SCCmec
      type III) hospital-associated methicillin-resistant Staphylococcus aureus in
      Taiwan. Strain Z172 also exhibits a vancomycin-intermediate and daptomycin
      nonsusceptible phenotype. 

PMID- 24309741
TI  - Draft Genome Sequence of the Psychrophilic and Alkaliphilic Rhodonellum
      psychrophilum Strain GCM71T.
AB  - Rhodonellum psychrophilum GCM71(T), isolated from the cold and alkaline submarine
      ikaite columns in the Ikka Fjord in Greenland, displays optimal growth at 5 to 10
      degrees C and pH 10. Here, we report the draft genome sequence of this strain,
      which may provide insight into the mechanisms of adaptation to these extreme
      conditions. 

PMID- 24309742
TI  - Draft Genome Sequence of Plant-Growth-Promoting Rhizobacterium Serratia fonticola
      Strain AU-AP2C, Isolated from the Pea Rhizosphere.
AB  - Plant health can be augmented by plant-growth-promoting rhizobacteria (PGPR) that
      confer biofertilizer, phytostimulation, and biocontrol activities. Herein, we
      provide the high-quality draft genome sequence of Serratia fonticola strain AU
      AP2C, a Gram-negative motile PGPR of the pea plant, conferring phosphate
      solubilization, ammonia production, and antifungal activity against Fusarium sp.
      The 4.9-Mb genome contains genes related to plant growth promotion and synthesis
      of siderophores. 

PMID- 24309743
TI  - Complete Genome Sequence of Bacillus thuringiensis Serovar Israelensis Strain HD
      789.
AB  - Bacillus thuringiensis is an important microbial insecticide for controlling
      agricultural pests. We report the finished genome sequence of Bacillus
      thuringiensis serovar israelensis strain HD-789, which contains genes encoding 7
      parasporal crystals consisting of Cry4Aa3, Cry4Ba5 (2 genes), Cry10Aa3, Cry11Aa3,
      Cry60Ba3, and Cry60Aa3, plus 3 Cyt toxin genes and 1 hemagglutinin gene. 

PMID- 24309744
TI  - Genome Sequence of Parvimonas micra Strain A293, Isolated from an Abdominal
      Abscess from a Patient in the United Kingdom.
AB  - Parvimonas micra is an important oral microbe that has the ability to grow and
      proliferate within oral biofilms and is involved in periodontal disease, leading
      to gingival bleeding, gingival recession, alveolar bone loss, and tooth mobility.
      However, occasionally these normally oral pathogens can cause infections at other
      sites in the body. We present the genome sequence of Parvimonas micra strain
      A293, a smooth Parvimonas micra strain isolated from an abdominal abscess from a
      patient at Barts Hospital, London, United Kingdom. 

PMID- 24309745
TI  - Draft Genome Sequences of Elizabethkingia anophelis Strains R26T and Ag1 from the
      Midgut of the Malaria Mosquito Anopheles gambiae.
AB  - Elizabethkingia anophelis is a species in the family Flavobacteriaceae. It is a
      dominant resident in the mosquito gut and also a human pathogen. We present the
      draft genome sequences of two strains of E. anophelis, R26(T) and Ag1, which were
      isolated from the midgut of the malaria mosquito Anopheles gambiae. 

PMID- 24309746
TI  - Both the anterior and posterior eyes function as photoreceptors for photoperiodic
      termination of diapause in the two-spotted spider mite.
AB  - Photoreceptors involved in photoperiodism in insects and mites can be either the
      retinal photoreceptors in the visual system or nonvisual extraretinal
      photoreceptors. Mites with no eyes have a clear photoperiodic response,
      suggesting the involvement of extraretinal photoreceptors in mite photoperiodism.
      In mites equipped with eyes, however, it is not known whether the retinal or
      extraretinal photoreceptors are involved in photoperiodism. The two-spotted
      spider mite Tetranychus urticae possesses two pairs of eyes. Adult females of
      this species terminate diapause in response to long days. To investigate whether
      the eyes function as photoperiodic photoreceptors in T. urticae, their eyes were
      ablated using a laser ablation system. Mites with their eyes intact terminated
      diapause under long days after low temperature exposure, whereas they remained in
      diapause under short days. Under constant darkness, they did not terminate
      diapause. When all eyes were removed, the mites remained in diapause even when
      they were maintained under long days. In contrast, the mites showed clear
      photoperiodic response when only the anterior or posterior eyes were removed.
      These results indicate that both the anterior and posterior eyes function as
      photoreceptors in photoperiodic termination of diapause in T. urticae. 

PMID- 24309747
TI  - Enslaving in a serial chain: interactions between grip force and hand force in
      isometric tasks.
AB  - This study was motivated by the double action of extrinsic hand muscles that
      produce grip force and also contribute to wrist torque. We explored interactions
      between grip force and wrist torque in isometric force production tasks. In
      particular, we tested a hypothesis that an intentional change in one of the two
      kinetic variables would produce an unintentional change in the other (enslaving).
      When young healthy subjects produced accurate changes in the grip force, only
      minor effects on the force produced by the hand (by wrist flexion/extension
      action) were observed. In contrast, a change in the hand force produced
      consistent changes in grip force in the same direction. The magnitude of such
      unintentional grip force change was stronger for intentional hand force decrease
      as compared to hand force increase. These effects increased with the magnitude of
      the initial grip force. When the subjects were asked to produce accurate total
      force computed as the sum of the hand and grip forces, strong negative
      covariation between the two forces was seen across trials interpreted as a
      synergy stabilizing the total force. An index of this synergy was higher in the
      space of "modes," hypothetical signals to the two effectors that could be changed
      by the controller one at a time. We interpret the complex enslaving effects
      (positive force covariation) as conditioned by typical everyday tasks. The
      presence of synergic effects (negative, task-specific force covariation) can be
      naturally interpreted within the referent configuration hypothesis. 

PMID- 24309748
TI  - Prior history of FDI muscle contraction: different effect on MEP amplitude and
      muscle activity.
AB  - Motor evoked potentials (MEPs) in the right first dorsal interosseous (FDI)
      muscle elicited by transcranial magnetic stimulation of left motor cortex were
      assessed in ten healthy subjects during maintenance of a fixed FDI contraction
      level. Subjects maintained an integrated EMG (IEMG) level with visual feedback
      and reproduced this level by memory afterwards in the following tasks: stationary
      FDI muscle contraction at the level of 40 +/- 5 % of its maximum voluntary
      contraction (MVC; 40 % task), at the level of 20 +/- 5 % MVC (20 % task), and
      also when 20 % MVC was preceded by either no contraction (0-20 task), by stronger
      muscle contraction (40-20 task) or by no contraction with a previous strong
      contraction (40-0-20 task). The results show that the IEMG level was within the
      prescribed limits when 20 and 40 % stationary tasks were executed with and
      without visual feedback. In 0-20, 40-20, and 40-0-20 tasks, 20 % IEMG level was
      precisely controlled in the presence of visual feedback, but without visual
      feedback the IEMG and force during 20 % IEMG maintenance were significantly
      higher in the 40-0-20 task than those in 0-20 and 40-20 tasks. That is, without
      visual feedback, there were significant variations in muscle activity due to
      different prehistory of contraction. In stationary tasks, MEP amplitudes in 40 %
      task were higher than in 20 % task. MEPs did not differ significantly during
      maintenance of the 20 % level in tasks with different prehistory of muscle
      contraction with and without visual feedback. Thus, in spite of variations in
      muscle background activity due to different prehistory of contraction MEPs did
      not vary significantly. This dissociation suggests that the voluntary maintenance
      of IEMG level is determined not only by cortical mechanisms, as reflected by
      corticospinal excitability, but also by lower levels of CNS, where afferent
      signals and influences from other brain structures and spinal cord are
      convergent.

PMID- 24309749
TI  - Assessing the benefits of multisensory audiotactile stimulation for overweight
      individuals.
AB  - We report an experiment designed to examine whether individuals who are
      overweight would perform differently when trying to detect and/or discriminate
      auditory, vibrotactile, and audiotactile targets. The vibrotactile stimuli were
      delivered either to the participant's abdomen or to his hand. Thirty-six young
      male participants were classified into normal, underweight, or overweight groups
      based on their body mass index. All three groups exhibited a significant benefit
      of multisensory (over the best of the unisensory) stimulation, but the magnitude
      of this benefit was modulated by the weight of the participant, the task, and the
      location from which the vibrotactile stimuli happened to be presented. For the
      detection task, the overweight group exhibited a significantly smaller benefit
      than the underweight group. In the discrimination task, the overweight group
      showed significantly more benefits than the other two groups when the
      vibrotactile stimuli were delivered to their hands, but not when the stimuli were
      delivered to their abdomens. These results might raise some interesting questions
      regarding the mechanisms underlying audiotactile information processing and have
      applied relevance for the design of the most effective warning signal (e.g., for
      drivers). 

PMID- 24309751
TI  - Severe compression of a bailout self-expanding chimney stent for rescuing the
      miscoverage of left common carotid artery during TEVAR of a type B aortic
      dissection.
AB  - A 54-year-old man who suffered from paraplegia due to type B aortic dissection
      was treated with a Valiant stent-graft. However, attempts to gain secure proximal
      sealing resulted in an inadvertent coverage of the left common carotid artery by
      the endograft. The blood flow in the left common carotid artery was restored by a
      transcarotid Smart Control stent in a chimney fashion. At 6- and 18-month follow
      up, computed tomography scan showed that the chimney stent was severely
      compressed by the stent graft, although the patient remained neurologically
      asymptomatic.

PMID- 24309752
TI  - [Secondary salmonella lesions in neonatal meningitis].

PMID- 24309750
TI  - Gamma band activity in the RAS-intracellular mechanisms.
AB  - Gamma band activity participates in sensory perception, problem solving, and
      memory. This review considers recent evidence showing that cells in the reticular
      activating system (RAS) exhibit gamma band activity, and describes the intrinsic
      membrane properties behind such manifestation. Specifically, we discuss how cells
      in the mesopontine pedunculopontine nucleus, intralaminar parafascicular nucleus,
      and pontine SubCoeruleus nucleus dorsalis all fire in the gamma band range when
      maximally activated, but no higher. The mechanisms involve high-threshold,
      voltage-dependent P/Q-type calcium channels, or sodium-dependent subthreshold
      oscillations. Rather than participating in the temporal binding of sensory events
      as in the cortex, gamma band activity in the RAS may participate in the processes
      of preconscious awareness and provide the essential stream of information for the
      formulation of many of our actions. We address three necessary next steps
      resulting from these discoveries: an intracellular mechanism responsible for
      maintaining gamma band activity based on persistent G-protein activation,
      separate intracellular pathways that differentiate between gamma band activity
      during waking versus during REM sleep, and an intracellular mechanism responsible
      for the dysregulation in gamma band activity in schizophrenia. These findings
      open several promising research avenues that have not been thoroughly explored.
      What are the effects of sleep or REM sleep deprivation on these RAS mechanisms?
      Are these mechanisms involved in memory processing during waking and/or during
      REM sleep? Does gamma band processing differ during waking versus REM sleep after
      sleep or REM sleep deprivation? 

PMID- 24309753
TI  - Time for Option B+? Prevalence and characteristics of HIV infection among
      attendees of 2 antenatal clinics in Buea, Cameroon.
AB  - As countries consider a wider use of triple antiretroviral therapy (ART) in
      pregnancy, which in recent World Health Organization guidelines is called Option
      B+, this study sought to explore the potential implications of adopting Option B+
      by characterizing HIV infection in pregnant women attending 2 semiurban antenatal
      clinics in Cameroon. In a descriptive cross-sectional study, consenting women
      were screened for HIV; positive samples were confirmed using an enzyme-linked
      immunosorbent assay test, and CD4 levels and HIV viral loads were determined
      using flow cytometry and reverse transcription-polymerase chain reaction,
      respectively. The seroprevalence of HIV in the 407 pregnant women screened was
      8.4% (95% confidence interval: 5.9%-11.5%). The majority (82.4%) of HIV-positive
      women had CD4 counts >350 cells/mm(3). A quarter (25%) had undetectable viral
      levels (<80 copies/mL). Adopting Option B+ in this setting would result in a 5
      fold increase in the number of HIV-infected pregnant women being placed on
      lifelong triple ART. 

PMID- 24309755
TI  - Investigation of HIV Incidence Rates in a High-Risk, High-Prevalence Kenyan
      Population: Potential Lessons for Intervention Trials and Programmatic
      Strategies.
AB  - Cost-effective HIV prevention programs should target persons at high risk of HIV
      acquisition. We conducted an observational HIV incidence cohort study in Kisumu,
      Kenya, where HIV prevalence is triple that of the national rate. We used referral
      and venue-sampling approaches to enroll HIV-negative persons for a 12-month
      observational cohort, August 2010 to September 2011, collected data using
      computer-assisted interviews, and performed HIV testing quarterly. Among 1292
      eligible persons, 648 (50%) were excluded for HIV positivity and other reasons.
      Of the 644 enrollees, 52% were women who were significantly older than men
      (P<.01). In all, 7 persons seroconverted (incidence rate [IR] per 100 person
      years=1.11; 95% confidence interval [CI] 0.45-2.30), 6 were women; 5 (IR=3.14;
      95% CI 1.02-7.34) of whom were <=25 years. Most new infections occurred in young
      women, an observation consistent with other findings in sub-Saharan Africa that
      women aged <=25 years are an important population for HIV intervention trials in
      Africa.

PMID- 24309754
TI  - Factors associated with late initiation of highly active antiretroviral therapy
      among young HIV-positive men and women aged 18 to 29 years in Canada.
AB  - Initiating highly active antiretroviral therapy (HAART) with low CD4 counts or
      AIDS-defining illnesses (ADIs) increases risk of treatment failure and death. We
      examined factors associated with late initiation among 18- to 29-year-olds within
      the Canadian Observational Cohort (CANOC) collaboration, a multi-site study of
      HIV-positive persons who initiated HAART after 2000. Late initiation was defined
      as beginning HAART with a CD4 count <200 cells/mm(3) and/or having a baseline
      ADI. Multivariable logistic regression was used to identify independent
      correlates of late initiation. In total, 1026 individuals (422 from British
      Columbia, 400 from Ontario, and 204 from Quebec) met our age criteria. At HAART
      initiation, median age was 27 years (interquartile range, 24, 28 years). A total
      of 412 individuals (40%) identified as late initiators. Late initiation was
      associated with female gender, age >25 years at initiation, initiating treatment
      in earlier years, and having higher baseline viral load. The high number of young
      adults in our cohort starting HAART late indicates important target populations
      for specialized services, increased testing, and linkages to care. 

PMID- 24309756
TI  - Ribulose-1,5-bisphosphate carboxylase as a nuclear and chloroplast marker.
AB  - The data on the primary structure of ribulose-1,5-bisphosphate
      carboxylase/oxygenase are reviewed. Examples of their use as markers and in the
      elucidation of the evolution, adaptation and function of this key enzyme are
      given. 

PMID- 24309757
TI  - Genetic analysis of brown planthopper resistance in twenty varieties of rice,
      Oryza saliva L.
AB  - The inheritance of resistance to brown planthopper, Nilaparvata lugens (Stol.),
      of 20 rice cultivars was studied. Single dominant genes that are allelic to Bph 3
      condition the resistance in cultivars 'Ptb 19', 'Gangala' (Acc. 7733), 'Gangala'
      (Acc. 15207), 'Horana Mawee', 'Kuruhondarwala', 'Mudu Kiriyal' and
      'Muthumanikam'. Single recessive genes that are allelic to bph 4 govern the
      resistance in cultivars 'Gambada Samba', 'Heenhoranamawee', 'Hotel Samba',
      'Kahata Samba', 'Kalukuruwee', 'Lekam Samba', 'Senawee', 'Sulai', 'Thirissa' and
      'Vellai Illankali'. The resistance in 'Ptb 33', 'Sudu Hondarwala', and 'Sinna
      Sivappu' is governed by one dominant and one recessive gene which segregate
      independently of each other. The dominant resistance genes in these cultivars
      appear allelic to either Bph 1 or Bph 3. Similarly, the recessive genes in these
      cultivars seem allelic to either bph 2 or bph 4. Further investigations are
      needed to conclusively determine the allelic relationships of resistance genes in
      'Ptb 33', 'Sudu Hondarwala' and 'Sinna Sivappu'. 

PMID- 24309758
TI  - The interspecific hybrid Petunia parodii * P. inflata and its relevance to
      somatic hybridization in the genus Petunia.
AB  - Attempts at the reciprocal cross between Petunia parodii and P. inflata using
      standard emasculation and pollination techniques failed. Limited pollen tube
      growth down the style in reciprocal crosses led to reproductive isolation between
      the self-compatible P. parodii and self-incompatible P. inflata. The
      interspecific hybrid was successfully produced by bud-pollination of P. parodii
      with P. inflata as the male parent in 22 percent of attempts, but not in the
      opposite direction. In vitro pollination of P. parodii ovaries with P. inflata
      pollen also produced hybrids. The small size of the ovary made it technically
      impossible to use P. inflata as the female parent for in vitro pollination. The
      interspecific hybrids were intermediate, as compared to the two parents, for six
      of the seven plant and flower characters measured. Furthermore, the hybrids had
      high pollen fertility, set abundant seed upon self-pollination, and readily inter
      crossed with the parental species. The results are consistent with a high degree
      of chromosomal homology in the parental species and with minor genetic divergency
      leading to reproductive isolation that is pre-zygotic in nature. Overcoming the
      barriers to cross-incompatibility by practical techniques resulted in fertile
      interspecific hybrids that segregated for parental characters. The potential
      value of employing the parental species in somatic hybridization experiments is
      discussed. 

PMID- 24309759
TI  - NADP-dependent aromatic alcohol dehydrogenase in polyploid wheats and their
      diploid relatives. On the origin and phylogeny of polyploid wheats.
AB  - The three major isoenzymes of the NADP-dependent aromatic alcohol dehydrogenase
      (ADH-B), distinguished in polyploid wheats by means of polyacrylamide gel
      electrophoresis, are shown to be coded by homoeoalleles of the locus Adh-2 on
      short arms of chromosomes of the fifth homoeologous group. Essentially codominant
      expression of the Adh-2 homoeolleles of composite genomes was observed in young
      seedlings of hexaploid wheats (T. aestivum s.l.) and tetraploid wheats of the
      emmer group (T. turgidum s.l.), whereas only the isoenzyme characteristic of the
      A genome is present in the seedlings of the timopheevii-group tetraploids (T.
      timopheevii s.str. and T. araraticum).The slowest-moving B(3) isoenzyme of
      polyploid wheats, coded by the homoeoallele of the B genome, is characteristic of
      the diploid species Aegilops speltoides S.l., including both its awned and
      awnless forms, but was not encountered in Ae. bicornis, Ae. sharonensis and Ae.
      longissima. The last two diploids, as well as Ae. tauschii, Ae. caudata, Triticum
      monococcum s.str., T. boeoticum s.l. (incl. T. thaoudar) and T. urartu all shared
      a common isoenzyme coinciding electrophoretically with the band B(2) controlled
      by the A and D genome homoeoalleles in polyploid wheats. Ae. bicomis is
      characterized by the slowest isoenzyme, B(4), not found in wheats and in the
      other diploid Aegilops species studied.Two electrophoretic variants of ADH-B,
      B(1) and B(2), considered to be alloenzymes of the A genome homoeoallele, were
      observed in T. dicoccoides, T. dicoccon, T. turgidum. s.str. and T. spelta,
      whereas B(2) was characteristic of T. timopheevii s.l. and only B(1) was found in
      the remaining taxa of polyploid wheats. The isoenzyme B(1), not encountered among
      diploid species, is considered to be a mutational derivative which arose on the
      tetraploid level from its more ancestral form B(2) characteristic of diploid
      wheats.The implication of the ADH-B isoenzyme data to the problems of wheat
      phylogeny and gene evolution is discussed. 

PMID- 24309760
TI  - An assessment of the production and performance of F1 hybrid wheats based on
      Triticum timopheevi cytoplasm.
AB  - This work reports on the production and yield assessment of F1 wheat hybrids from
      crosses between cytoplasmic male sterile lines, with Triticum timopheevi
      cytoplasm, and cultivars with fertility restoring genes.In four years of trials
      conducted between 1974 and 1977, only three F1 hybrids out of a total of 168
      yielded significantly more than the control variety 'Maris Huntsman', which
      currently occupies a substantial proportion of the area planted with winter wheat
      in the UK. Because of the rapid increase in yield of conventional wheat
      varieties, which has already led to varieties which outyielded 'Maris Huntsman',
      the yield advantage of these F1 hybrids is insufficient for them to be developed
      as commercial varieties.The efficient production of uncontaminated male sterile
      and F1 seed presents problems of isolation and a difficult biological problem in
      increasing the cross breeding potential of maintainer and restorer lines. These
      together with selection for other parental characters such as restoration, short
      straw and resistance to sprouting make the development of F1 hybrids more
      difficult and expensive than that of conventional varieties. 

PMID- 24309761
TI  - Revision of SAT chromosome number in Triticum monococcum with respect to
      nucleolar organizers activity.
AB  - Six varieties of Triticum monococcum were analysed by means of the nucleolar
      test; i.e., estimation of the maximum number of primary nucleoli per nucleus. All
      of the varieties exhibited 4 primary nucleoli in telophase and early interphase.
      Following detailed karyological analysis four SAT chromosomes in all six
      karyotypes were found in accordance with the maximum nucleolar number. Secondary
      constrictions and microsatellites were localised on the short arms of chromosome
      pairs 3 and 5. A new order of the chromosomes in the idiogram of Tr. monococcum
      is proposed. 

PMID- 24309762
TI  - Genetic architecture of yield and components of yield in mustard (Brassica juncea
      (L.) Czern & Coss.).
AB  - Seed yield and some of its primary components, viz. primary and secondary
      branches, siliquae per plant, seeds per siliqua and seed size, were studied in
      the F1 and F2 populations of five intervarietal crosses of mustard. The parental
      cultivars represented a fairly wide range of variation for all the characters.
      Both additive and dominance components were important for these traits and the
      gene actions were dependent upon the particular cross combination involved.
      Degrees of dominance were variable within each trait and inconsistent over the
      generations. The estimates of broad sense heritability and genetic advance were
      moderate to high, indicating that direct selection on the basis of primary
      branches and seeds per siliqua would be successful in the early segregating
      generations. Only one group of genes was detected in these traits. None of the F1
      hybrids were higher than the highest yielding cultivar 'Laha 101'. The production
      of hybrids higher than this cultivar is not possible without the introduction of
      genes from other sources. 

PMID- 24309763
TI  - Response: Facial nuclear degeneration on MRI in bulbar onset amyotrophic lateral
      sclerosis.

PMID- 24309764
TI  - A new family of sunlight-driven bifunctional photocatalysts based on TiO2
      nanoribbon frameworks and bismuth oxohalide nanoplates.
AB  - By taking advantage of the structural affinity between bismuth oxohalide and
      TiO2, we successfully prepare a family of hybrid frameworks via the designated
      growth of bismuth oxohalide nanoplates on TiO2 nanoribbons, and propose them as
      sunlight-driven bifunctional photocatalysts for all-weather removal of
      pollutants. The structural variability of bismuth oxohalide allows the optical
      absorption of the hybrid framework to be monotonically tuneable across the
      visible spectrum. Meanwhile, the hybridization greatly increases the surface
      roughness of the frameworks and enables the frameworks to harvest more photons to
      participate in photocatalytic reactions. Furthermore, the hybridization
      establishes two potential gradients to promote the separation of photo-induced
      electron-hole pairs: the internal electrical field perpendicular to the wide
      surfaces of bismuth oxohalide nanoplates and across the semiconductor
      semiconductor heterojunction. Owing to the synergetic effects of the permeable
      mesoporous architecture, the intense visible light absorption, and the efficient
      charge separation, the hybrid frameworks are capable of all-weather removal of
      pollutants: they utilize the inter-ribbon pores to gather pollutants in the dark
      (behaving as collectors) and they rapidly degrade the pollutants in the day
      (behaving as photocatalysts). In particular, the BiOBr@TiO2 framework exhibits
      very impressive sunlight-driven photocatalytic activity, which is much higher
      than commercially available P25 TiO2 under the same conditions.

PMID- 24309765
TI  - The hole and the whole.

PMID- 24309766
TI  - The caries burden.

PMID- 24309767
TI  - Vaccinating boys against HPV.

PMID- 24309768
TI  - Not just the joints.

PMID- 24309782
TI  - Truth or consequences: the potential implications of short-term cosmetic
      orthodontics for general dental practitioners.
AB  - Until recently, cosmetic dentistry has focused on the use of traditional
      restorative techniques, bleaching and the so-called facial rejuvenators such as
      injectable dermal fillers and Botox. More latterly, the short-term use of
      aesthetic removable aligners and ceramic fixed appliance brackets have been
      promoted for use by general dental practitioners as a means of minimising the
      invasive amount of restorative dental treatment that would otherwise be required
      to achieve the desired degree of aesthetic improvement. Nevertheless, there are
      inherent risks and complications associated with short-term orthodontic
      treatments that are deliberately limited in their outcomes and these, together
      with the potential ramifications for the long-term dental health of patients, are
      discussed. 

PMID- 24309783
TI  - Facial cutaneous sinuses of dental origin - a diagnostic challenge.
AB  - It is common for practitioners to misdiagnose the cause of facial cutaneous sinus
      tracts, failing to recognise that many have an odontogenic cause. Chronic
      infection around the apex of a dental root can drain to the mouth or less
      commonly to the skin via a sinus tract. Dental symptoms are not always present
      and this confuses the clinical picture further. Failure to identify an
      odontogenic cause may result in unnecessary and ineffective treatment.
      Elimination of dental infection via tooth extraction or root canal treatment
      leads to resolution of the cutaneous sinus. We present a series of cutaneous
      draining sinuses of dental origin that resolved rapidly following dental
      treatment and hope to highlight the importance of including odontogenic infection
      in the differential diagnosis of such a lesion in the head and neck. 

PMID- 24309788
TI  - Summary of: dental practitioners and a digital future: an initial exploration of
      barriers and incentives to adopting digital technologies.
AB  - BACKGROUND: Digital technologies are proliferating into dental practices. While
      their technical attributes have often been studied, it remains unclear why some
      dentists adopt and use these technologies more than others. AIM To explore the
      incentives for and barriers against accepting and using digital dental
      technologies. METHOD: Eleven semi-structured qualitative interviews were
      conducted with experts in dentistry, dental technology and dental education in
      the Netherlands. RESULTS: Dentists' acceptance and use of digital technologies
      are to varying degrees driven by the perceived advantages over analogue methods,
      perceived influence on treatment quality, dentists' personal and professional
      orientation, and social influence from peers and external groups. These effects
      are complemented by personal and dental-practice characteristics. CONCLUSIONS:
      The findings suggest that there are large differences in motivation to adopt and
      use digital technologies between early adopters, late adopters and non-adopters,
      which should be examined in greater detail. We recommend that educators,
      dentists, and representatives of the dental industry who deal with the diffusion
      of these technologies take account of dentists' widely different attitudes to
      digitalisation.

PMID- 24309789
TI  - Applicants' perceptions on the multiple mini-interview process as a selection
      tool for dental and therapy and hygiene students.
AB  - OBJECTIVE: This research details and quantifies applicants' perceptions towards
      multiple mini-interviews as a selection tool. MATERIALS AND METHODS: BDS and DCP
      (therapy and hygiene) candidates who secured a multiple mini-interview (MMI)
      completed a questionnaire based on the thematic analysis of the previous year's
      multiple mini-interviews. The questionnaire explored the candidates' feelings
      with reference to the interview process and the stations used on the MMI process.
      RESULTS: Of 235 BDS and 62 therapy and hygiene interviewees, 231 (98.3%) and 61
      (96.7%) completed or partially completed the questionnaire. Demographic data
      revealed that 61.9% (143) of the BDS interviewees were female and 86.7% were
      female (52) in the therapy and hygiene cohort. The majority of interviewees came
      from schools in England and received a state education. While 69.6% of the BDS
      interviewees had experience of an interview before their MMI, this was down to
      58.3% in the hygiene and therapy interviewees. Binomial statistical calculations
      and chi-squared tests of independence of categorical variables on nominally
      scaled data revealed statistically significant differences (p >0.001) and both
      groups of students were positive regarding the selection process (p >0.001).
      Overall there was similarity between groups with respect to the themes evaluated
      and stations used in the MMI process, however, statistical analysis did highlight
      areas of difference. There were 54 separate free text comments recorded but
      qualitative analysis failed to identify any themes that had not been previously
      identified. CONCLUSION: This research did not reveal any new emergent themes in
      relation to the MMI process between two different cohorts of students but did
      reveal general similarities and some specific areas of difference.

PMID- 24309790
TI  - Simulation training for dental foundation in oral and maxillofacial surgery - a
      new benchmark.
AB  - Simulation training involves reproducing the management of real patients in a
      risk-free environment. This study aims to assess the use of simulation training
      in the management of acutely ill patients for those in second year oral and
      maxillofacial surgery dental foundation training (DF2s). DF2s attended four full
      day courses on the recognition and treatment of acutely ill patients. These
      incorporated an acute life-threatening events: recognition and treatment
      (ALERT(TM)) course, simulations of medical emergencies and case-based discussions
      on management of surgical inpatients. Pre- and post-course questionnaires were
      completed by all candidates. A maximum of 11 DF2s attended the course. The
      questionnaires comprised 1-10 rating scales and Likert scores. All trainees
      strongly agreed that they would recommend this course to colleagues and all
      agreed or strongly agreed that it met their learning requirements. All DF2s
      perceived an improvement in personal limitations, recognition of critical
      illness, communication, assessing acutely ill patients and initiating treatment.
      All participants felt their basic resuscitation skills had improved and that they
      had learned new skills to improve delivery of safety-critical messages. These
      techniques could be implemented nationwide to address the more complex
      educational needs for DF2s in secondary care. A new benchmark for simulation
      training for DF2 has been established. 

PMID- 24309791
TI  - Direct access to DCPs: what are the potential risks and benefits?
AB  - The decision by the General Dental Council (GDC) in March 2013 to remove the
      requirement for a patient to first see a dentist before any treatment by a dental
      care professional, has been seen by some as controversial. The GDC has stated
      patient safety is the utmost priority and a literature review on direct access in
      dental and other healthcare fields was commissioned by the GDC in April 2012. The
      review considered whether any expansion of direct access would involve increased
      risk to patients, either by treatment or through failure to recognise and refer
      problems outside DCPs' clinical remit. This paper is an edited version of the
      results of that literature review. 

PMID- 24309806
TI  - Juliette Reeves: 'We are going to find ourselves at the leading edge of
      preventive medicine'. Interview by Ruth Doherty.
AB  - Juliette Reeves, dental hygienist, on what we should be eating in the future,
      what is in store for preventive dentistry and the importance of research in
      establishing the links between oral diseases, nutrition and general health. 

PMID- 24309807
TI  - Dentist suicides.
AB  - EDITOR'S COMMENT: The following article highlights the very sad circumstances
      surrounding the suicide of a colleague earlier in the year. We received the text
      below from Paul Hood as a submission to 'Letters to the editor' for the BDJ and
      reproduce it here in full. My initial reaction was that the letter contained
      sentiments and thoughts that would resonate with readers but that it over long
      for our pages and needed some general 'tidying up' before we could publish it. I
      replied by e-mail suggesting this and offering editorial help if he wished. Very
      sadly I did not receive a reply as Paul had committed suicide. Subsequently John
      Renshaw contacted me and suggested that we might publish the letter together with
      an introduction. We do this, with full, and gratefully received, permission from
      Paul's widow, to whom we also extend our sincere condolences.

PMID- 24309814
TI  - Dental practitioners and a digital future: an initial exploration of barriers and
      incentives to adopting digital technologies.
AB  - BACKGROUND: Digital technologies are proliferating into dental practices. While
      their technical attributes have often been studied, it remains unclear why some
      dentists adopt and use these technologies more than others. AIM To explore the
      incentives for and barriers against accepting and using digital dental
      technologies. METHOD: Eleven semi-structured qualitative interviews were
      conducted with experts in dentistry, dental technology and dental education in
      the Netherlands. RESULTS: Dentists' acceptance and use of digital technologies
      are to varying degrees driven by the perceived advantages over analogue methods,
      perceived influence on treatment quality, dentists' personal and professional
      orientation, and social influence from peers and external groups. These effects
      are complemented by personal and dental-practice characteristics. CONCLUSIONS:
      The findings suggest that there are large differences in motivation to adopt and
      use digital technologies between early adopters, late adopters and non-adopters,
      which should be examined in greater detail. We recommend that educators,
      dentists, and representatives of the dental industry who deal with the diffusion
      of these technologies take account of dentists' widely different attitudes to
      digitalisation.

PMID- 24309815
TI  - Quality of 'commercial-off-the-shelf' (COTS) monitors displaying dental
      radiographs.
AB  - BACKGROUND: A computer display monitor used for interpreting dental images should
      have a maximum luminance of 171 cd/m(2). A monitor used for clinical review
      should have a maximum luminance of 100 cd/m(2). OBJECTIVE: To compare luminance
      and ambient lighting measurements for a selection of computer display monitors in
      different locations of a dental teaching hospital to available guidelines. To
      assess six commercial off-the-shelf (COTS) monitors from the radiology department
      of the dental teaching hospital after calibration to the Digital Imaging and
      Communications in Medicine Part 14: Greyscale Standard Display Function (DICOM
      part 14: GSDF). DESIGN: Data collection. METHOD: Luminance and illuminance
      measurements were taken for a selection of monitors used for clinical
      applications throughout a dental teaching hospital. Conformance data were
      recorded for six COTS monitors from the radiology department following
      calibration to the DICOM part 14: GSDF. RESULTS None of the tested monitors had a
      maximum luminance value that was appropriate for image interpretation and the
      ambient lighting in the vicinity of the monitors was also set to inappropriate
      levels for image interpretation. The quality of conformance to the DICOM part 14:
      GSDF varied among the calibrated COTS monitors in the radiology department.
      CONCLUSIONS: : It is important that display devices used for dental radiology are
      quality assured. Consideration should be given to ensure that monitors used for
      dental radiological interpretation have a maximum luminance that meets available
      guidelines. These monitors should be standardised to the DICOM part 14: GSDF and
      the illumination of the reporting environment should be controlled.

PMID- 24309816
TI  - Alternative splicing of Myb-related genes MYR1 and MYR2 may modulate activities
      through changes in dimerization, localization, or protein folding.
AB  - Arabidopsis genes MYR1 and MYR2 are regulators of flowering time under low light
      intensity. These Myb-related genes are expressed as alternative splice variants
      affected in their coiled-coil and DNA-binding domains. We tested whether
      alternative splicing could affect dimerization and localization of MYR1 and MYR2,
      thereby potentially affecting their activity. Using MYR1 as a model for variants
      within the coiled-coil region, we detected 2 types of homodimers. For MYR2,
      alternative splicing in the DNA-binding Myb-like domain abolished the ability of
      MYR2 to dimerize. Alternative splicing in the coiled-coil domain did not affect
      nuclear localization, as determined by transient expression in tobacco, while
      alternative splicing in the DNA-binding domain of MYR2 yielded a distinct
      intranuclear localization pattern that may reflect changes in phosphorylation
      dependent protein folding. Thus alternative splicing of these genes may result in
      changes in dimerization or protein folding resulting in changes in activity and
      abundance of MYR1 or MYR2 protein. 

PMID- 24309817
TI  - Homeobox genes expressed during echinoderm arm regeneration.
AB  - Regeneration in echinoderms has proved to be more amenable to study in the
      laboratory than the more classical vertebrate models, since the smaller genome
      size and the absence of multiple orthologs for different genes in echinoderms
      simplify the analysis of gene function during regeneration. In order to
      understand the role of homeobox-containing genes during arm regeneration in
      echinoderms, we isolated the complement of genes belonging to the Hox class that
      are expressed during this process in two major echinoderm groups: asteroids
      (Echinaster sepositus and Asterias rubens) and ophiuroids (Amphiura filiformis),
      both of which show an extraordinary capacity for regeneration. By exploiting the
      sequence conservation of the homeobox, putative orthologs of several Hox genes
      belonging to the anterior, medial, and posterior groups were isolated. We also
      report the isolation of a few Hox-like genes expressed in the same systems. 

PMID- 24309818
TI  - Properties of a membrane-bound triglyceride lipase of rapeseed (Brassica napus
      L.) cotyledons.
AB  - The properties of the alkaline lipase activity (EC 3.1.1.3) that was recovered
      almost completely from a microsomal membrane fraction of 4-d-old rapeseed
      (Brassica napus L.) cotyledons were studied employing a titrimetric test
      procedure. The apparent KM was 6.5 mmol l(-1), with emulgated sunflower oil as
      the substrate. The products of triglyceride hydrolysis in vitro were glycerol,
      free fatty acids, and minor amounts of mono- and diglycerides. Maximum lipase
      activity depended on the preincubation of the lipolytic membrane fraction in 0.15
      mol l(-1) NaCl and on the presence of at least 0.1 mol l(-1) NaCl in the test
      mixture. Desoxycholate and up to 0.1 mol l(-1) CaCl2 also activated the enzyme
      while EDTA and detergents such as trito x-100, digitonin, tween 85, and sodium
      dodecylsulfate were inhibitory. The rapeseed lipase displayed a conspicuous
      substrate selectivity among different plant triglycerides; the activity was
      inversely correlated with the oleic acid content of the oils. Water-soluble
      triacetin and the phospholipid lecithin were not hydrolyzed. Increasing amounts
      of free fatty acids reduced lipase activity; erucic acid, a major component of
      rapeseed oil, exhibited the strongest effect, suggesting a possible role in the
      regulation of lipase activity in vivo. The data demonstrate that the lipolytic
      membrane fraction houses a triglyceride lipase with properties similar to other
      plant and animal lipases. It can both qualitatively and quantitatively account
      for the fat degradation in rapeseed cotyledons. The evidence that provides
      further reason to acknowledge the membranous appendices of the spherosomes as the
      intracellular site of lipolysis is discussed. 

PMID- 24309819
TI  - Occurrence and biosynthesis of catalase at different stages of seed maturation.
AB  - It was to be shown whether during the biogenesis of microbodies some of their
      components were already present in the cell prior to the organelle's assembly. To
      this end, the occurrence and properties of catalase in soluble and particular
      fractions of ripening cucumber seeds were examined. Homogenates of seeds from
      ripening fruits were fractionated by isopycnic density gradient centrifugation,
      and thus catalase was found in three different fractions: as a soluble enzyme in
      the gradient supernatant, as a membrane fraction at density d=1.18 kg l(-1), and
      in association with microbodies. In the early steps of seed formation, catalase
      was detected at density d=1.18 kg l(-1) and in the gradient supernatant. At a
      later stage of seed maturation, however, catalase was primarily associated with
      microbodies which exhibited an equilibrium density of d=1.23 kg l(-1). M r as
      well as subunit M r of catalase were determined, and their close immunological
      relationship to leaf peroxisomal catalase and glyoxysomal catalase was
      demonstrated. Biosynthesis of catalase at different stages of seed maturation was
      investigated by in vivo labeling with L-[(35)S]methionine, L-[(14)C]leucine and
      delta-[(3)H]aminolaevulinic acid. Electrophoretic analysis of de novo synthesized
      catalase subunits revealed the occurrence of a heavy form (M r 57,500) in the
      soluble fraction; this form was preferentially labeled. A light form, M r 53,500,
      was detected in microbodies and also in the soluble fraction. The findings lend
      support to the hypothesis that the rate of catalase synthesis is highest in an
      early stage of seed formation, when globulins have already been formed, but
      before de novo synthesis of malate synthase has commenced. Prior to microbody
      assembling, a cytoplasmic pool of catalase was labeled. 

PMID- 24309820
TI  - Fusicoccin receptors. Evidence for endogenous ligand.
AB  - The binding of fusicoccin to the microsomal preparations of maize roots in vitro
      is increased several-fold when segments of the tissue are washed for 2 h in
      distilled water before homogenization. Addition of freeze-dried wash solution to
      microsomal preparations of spinach leaves or fresh roots, washed roots, or
      coleoptiles of maize inhibited the binding of fusicoccin to particulate
      fractions. The freeze-dried material also blocked fusicoccin-promoted H(+)
      extrusion from maize root segments. Roots may contain one or more water-soluble
      compounds competing with fusicoccin at the receptor level; such ligands might
      play a physiological role as modulators of the H(+)/K(+) exchange system in
      higher plants. 

PMID- 24309821
TI  - Suitable conditions for characterization, identification, and isolation of the
      mRNA of the small subunit of ribulose-1,5-bisphosphate carboxylase from Nicotiana
      sylvestris.
AB  - The products synthesized in vitro by messenger RNA (mRNA) extracted from
      Nicotiana sylvestris were analyzed by electrophoresis on polyacrylamide slab
      gels. Only three of the major polypeptides synthesized are considered here: P55,
      P32, and P20. P55 and P32 were translated from chloroplast mRNA. P55 corresponds
      to the large subunit of ribulose-1,5-bisphosphate (RuP2) carboxylase; P32 is
      probably a chloroplast membrane protein. P20, the polypeptide synthesized from
      cytoplasmic poly(A)(+) RNA, is the precursor of the small subunit of RuP2
      carboxylase. The balance between P20 and P32, in which their relative proportions
      varied inversely, was regulated by the age of the leaves and the time of
      illumination; we took advantage of this phenomenon to isolate the mRNA from the
      small subunit in relatively large amounts. This mRNA has a molecular weight of
      350,000. 

PMID- 24309822
TI  - Pollen tube growth following compatible and incompatible intraspecific
      pollinations in Petunia hybrida.
AB  - The observation that both compatible and incompatible pollen tubes grow at
      identical speeds on the stigma in many plants with 'gametophytically controlled'
      self-incompatibility (SI) systems has, in Petunia, been extended to cover all
      other facets of pollen behaviour on this tissue. On entry into the stylar
      transmitting tissue both types of tubes accelerate, but the compatible achieve a
      higher terminal velocity than do the incompatible, which eventually slow and
      stop. Grafting experiments show that the top 1 mm of the stylar tissue can play
      an important role in determining the future development of the pollen tube.
      Following mixed pollinations, proportionally too many 'compatible' pollen tubes
      reach the ovary than would be expected from the results of 'pure' compatible and
      incompatible pollinations indicating that incompatible pollen in some way helps
      'prime' the style for growth of compatible pollen tubes. This data is considered
      in terms of recent structural studies of these tissues, and related to the
      pollination conditions pertaining to Petunia populations in the field. 

PMID- 24309823
TI  - Seasonal variation of enzyme activities in Laminaria hyperborea.
AB  - The patterns of seasonal variation of enzyme levels in the brown alga Laminaria
      hyperborea (Gunn.) Fosl. have been investigated for the following enzymes:
      Ribulosebisphosphate-carboxylase (EC 4.1.1.39), phosphoenolpyruvate-carboxykinase
      (EC 4.1.1.32), glyceraldehyde-3-phosphate-dehydrogenase (NADP dep., EC 1.2.1.12),
      malate-dehydrogenase (NAD dep., EC 1.1.1.37), L-aspartate-2-oxoglutarate
      aminotransferase (EC 2.6.1.1), and mannitol-l-phosphate-dehydrogenase (EC
      1.1.1.17). The first four enzymes exhibit a circannual periodicity, characterized
      by a pronounced 'spring-maximum' of enzyme activity in April and May. As a
      consequence, the phylloid can maintain high metabolic rates from early spring on,
      although water temperature has then only slightly risen above the annual minimum.
      This findings is discussed in relationship to the growth- and developmental cycle
      of L. hyperborea and to the seasonal variation of photosynthesis and light
      independent CO2-fixation. The seasonal pattern, outlined above, correlates well
      with the circannual fluctuations of the nitrogen content of the sea and with the
      variation of the internal nitrogen- and nitrate-content of the alga. This
      coincidence may indicate that nitrogen levels play an important role in the
      regulation of enzyme activities and, hence, the metabolic capacities of L.
      hyperborea. 

PMID- 24309825
TI  - Localization of sulfolipid labeling within cells and chloroplasts.
AB  - Spinach chloroplasts were purified on gradients of Percoll which preserved
      envelope impermeability and CO2-dependent oxygen evolution in the light.
      Application of (35)SO4" to purified chloroplasts resulted in a light-dependent
      labeling of a lipid component which was indentified as sulfoquinovosyl
      diacylglycerol. Fractionation of chloroplasts showed that after 5 min of labeling
      most of the newly synthesized sulfolipid was present in thylakoids. Only a small
      percentage was recovered from the envelopes. Molecular species from envelopes and
      thylakoids were identical. The molecular species did not change during incubation
      times ranging from 5 min up to 4.5 h. Mesophyll protoplasts from (35)SO4"-labeled
      oat primary leaves were gently disrupted and separated into organelles by sucrose
      gradient centrifugation. Labeled sulfolipid was located almost exclusively in the
      chloroplasts. This, in combination with the experiments carried out with isolated
      chloroplasts, indicates that the final assembly steps in the biosynthesis of
      sulfolipid are confined to the chloroplasts. 

PMID- 24309824
TI  - Regular arrays of intramembranous particles in the plasmalemma of guard cell and
      mesophyll cell protoplasts of Vicia faba.
AB  - Freeze fractures of the plasmalemma membranes of guard-cell and mesophyll
      protoplasts of Vicia faba demonstrate that the inner monolayer of the plasmalemma
      is compartmentalized into areas with distinct, highly organized structures.
      Between areas of intramembranous particles dispersed randomly on a relatively
      smooth fracture face, membrane domains showing an extremely regular planar,
      hexagonal array of particles are interspersed. The dimensions of these hexagonal
      lattices are about 0.5 MUm in diameter, the center-to-center spacing is about 22
      nm, and the particle size is about 9 nm. The particle in the hexagonal arrays are
      accompanied by complementary pits in the opposite monolayer fracture of the
      plasmalemma membrane.The freeze-fracture preparation was performed by using an
      improved Leybold Bioetch device which provides a sufficiently high cooling rate
      and allows the omission of cryoprotectants, like glycerol. 

PMID- 24309826
TI  - Ultrastructural localization of silver deposits in the receptacle cells of
      carnation flowers.
AB  - Carnations were treated with a silver thiosulphate complex to prevent wilting of
      the flowers. The ultrastructural localization of silver and sulphur in the
      receptacle tissue was investigated by electron microscopy. Electron-dense
      deposits were present in the receptacle tissue. Coarse-grained deposts (diam. 60
      100 nm) were predominantly observed at the inner side of the cell wall, whereas
      fine-grained deposits (diam. 20-60 nm) were predominantly present inside the cell
      wall region and in the intercellular spaces. These particles were analyzed for
      chemical elements by X-ray analytical electron microscopy (Philips EM 400 plus
      Edax energy dispersive analyzer, type 711). In both types of deposits, the
      presence of silver and sulphur was verified. Point analysis revealed that in both
      precipitates the S/Ag ratio was of the same order. 

PMID- 24309827
TI  - Vacuolar reorganization in the motor cells of Albizzia during leaf movement.
AB  - During the leaf movements of Albizzia julibrissin Durazzini, volume changes in
      the motor cells of the pulvinule (tertiary pulvinus) are closely correlated with
      a reversible reorganization of the vacuolar compartment. Motor cells have central
      vacuoles when expanded, but become multivacuolate during the time the cell volume
      decreases. The central vacuole reforms - apparently by fusion of small vacuoles -
      during motor-cell expansion. The volume changes of the vacuolar compartment
      account for all of the change in the size of the protoplast, while the
      cytoplasmic volume remains constant during the leaf movements. 

PMID- 24309828
TI  - Effect of abscisic acid on membrane potential and transport of glucose and
      glycine in Lemna gibba G1.
AB  - The membrane potential of Lemna gibba G1 was measured with a microelectrode;
      glucose and glycine uptake were measured with (14)C-labeled substances. The
      membrane potential was increased by 85 mV on the average, after the plants had
      been pretreated with 10 MUM abscisic acid (ABA) for more than 30 min. This effect
      is not linked to the endogenous level of soluble sugars. The concentration of
      these soluble sugars was increased to more than 200% by pretreatment of the
      plants with ABA, however, the respiration of the plants was not affected. ABA
      stimulated uptake of glucose and glycine. Glucose- and glycine-dependent
      depolarization and repolarization of the membrane was altered: depolarization was
      less and repolarization was slower; during uptake of glycine, the first typical
      phase of repolarization was suppressed. The data suggest that ABA interferes with
      the primary steps of substrate uptake. 

PMID- 24309829
TI  - Radioimmunoassays for the differential and direct analysis of free and conjugated
      abscisic acid in plant extracts.
AB  - Two radioimmunoassays have been developed which allow the parallel quantitation
      of free as well as conjugated natural (+)-abscisic acid (ABA) directly and
      separately, in unpurified plant extracts. The differential specificity of
      antisera has been achieved by coupling ABA through C1 (for total ABA
      determination) or C4 (for free ABA determination), respectively, to proteins to
      obtain the immunogenic conjugates. Compounds structurally related to ABA, such
      as, dihydrophaseic acid or phaseic acid, do not interfere with either of the
      assays, even when present in more than ten-fold excess. Other related compounds,
      such as, violaxanthin or xanthoxin, do not cross react at all. Both antisera
      respond to (+)-ABA but show very low immunoreactivity with (-)-ABA. As little as
      27 pg of ABA (serum for free ABA) or 47 pg (serum for total ABA) may be detected
      and the measuring ranges are from 0.2-8 and 0.2-30 pmol, respectively. Average
      recoveries are greater than 99%. Using these assays, more than 100 samples can be
      assayed for free and conjugated ABA per day. Levels of free ABA, as determined by
      radioimmunoassay (RIA), correlated well with those reported in the literature.
      Levels of conjugated ABA were found to be generally higher than previously
      reported for ABA after alkaline hydrolysis of the extracts. Conjugated ABA
      accumulates during aging of leaves and levels of conjugated ABA up to 17-fold
      higher than those of free ABA have been detected in senescent leaves of
      Hyoscyamus niger L. Evidence was obtained for the presence of ABA conjugates
      other than the glucose ester in some plants. 

PMID- 24309830
TI  - Proton excretion and cell expansion in bean leaves.
AB  - Light-induced expansion of Phaseolus vulgaris L. leaf cells is accompanied by
      increased cell-wall plasticity. The possibility that leaf-cell walls are loosened
      by excreted protons has been investigated. First, light causes acidification,
      detected at the leaf surface, within 5-15 min. Growth starts 10-20 min after
      exposure to light. Second, exogenous acid induces loosening of isolated leaf cell
      walls. Third, infiltration of the tissue with a neutral buffer inhibits light
      induced growth. Fourth, fusicoccin stimulates growth of as well as H(+) excretion
      by bean leaf cells, without light. These findings show that the acid-growth
      theory is applicable to light-induced growth of leaf cells, and indicate that
      light-induced proton excretion initiates cell enlargement in leaves. 

PMID- 24309831
TI  - Analysis of light-controlled accumulation of carotenoids in mustard (Sinapis alba
      L.) seedlings.
AB  - Carotenoid accumulation in the cotyledons of the mustard seedling (Sinapis alba
      L.) is controlled by light. Besides the stimulatory function of phytochrome in
      carotenogenesis the experiments reveal the significance of chlorophyll
      accumulation for the accumulation of larger amounts of acrotenoids. A specific
      blue light effect was not found. The data suggest that light exerts its control
      over carotenoid biogenesis through two separate mechanisms: A phytochrome
      regulation of enzyme levels before a postulated pool of free carotenoids, and a
      regulation by chlorophyll draining the pool by complex-formation. 

PMID- 24309832
TI  - Effects of the plant host on the detergent sensitivity and viability of Rhizobium
      bacteroids.
AB  - Bacteroids prepared from different legume species showed large differences in
      detergent sensitivity as judged by changes in turbidity and the release of
      cytochrome c oxidase activity after detergent treatments. There was a strong
      correlation between the detergent sensitivity and non-viability of bacteroids.
      Differences in the detergent sensitivity of bacteroids were determined by the
      plant host rather than the Rhizobium strain or the effectiveness of the
      symbiosis. The most common level of detergent sensitivity observed amongst
      bacteroids from 34 legume species was intermediate between lupin bacteroids and
      brothcultured bacteria. 

PMID- 24309834
TI  - Erratum.

PMID- 24309833
TI  - The endoplasmic reticulum of mung-bean cotyledons: Quantitative morphology of
      cisternal and tubular ER during seedling growth.
AB  - The ultrastructure of the endoplasmic reticulum (ER) in storage parenchyma cells
      in the cotyledons of mung beans (Vigna radiata L.) was examined during
      germination and seedling growth. Two different methods were used to visualize the
      ER: thin (0.08 MUm) sections of tissue fixed in formaldehyde and glutaraldehyde
      and post-fixed with osmium tetroxide, and thick (1 MUm) sections of tissue fixed
      in buffered aldehyde and post-fixed with zinc iodide-osmium tetroxide (ZIO).
      Changes in relative amounts of ER were quantified by morphometry (stereology).The
      ER occurs in two forms: a cisternal form with associated ribosomes which can be
      seen at all stages from imbibition to cotyledon senescence, and a tubular form
      which initially has associated ribosomes. Stereoscopic images of thick sections
      of cotyledons of 2-day-old seedlings show that the tubular ER consists of a three
      dimensional array of interconnecting tubules which have numerous connections with
      the cisternal ER. The network of tubules and cisternae extends throughout the
      cytoplasm enveloping the protein bodies. Germination and seedling growth are
      accompanied by a reduction in the total volume occupied by the ER. This reduction
      is the result of a preferential loss of tubular ER and occurs largely before
      protein mobilization. Cisternal ER decreases during the first 48 h of imbibition
      and seedling growth, but storage cells subsequently show an increase in cisternal
      ER just prior to and during the period of protein mobilization. Cisternal ER
      remains conspicuous during the last phase of reserve mobilization when starch is
      broken down and the cells are starting autophagy. 

PMID- 24309835
TI  - Evidence for including lutein and zeaxanthin in oral supplements for age-related
      macular degeneration.

PMID- 24309836
TI  - Super-resolution imaging of SERS hot spots.
AB  - Surface-enhanced Raman scattering (SERS) hot spots occur when molecules are
      positioned near regions of strongly enhanced electromagnetic fields on the
      surface of nano-featured plasmonic substrates. The emission from the molecule is
      coupled out into the far field by the plasmon modes of the substrate, but due to
      the diffraction-limit of light, the properties of this coupled molecule-plasmon
      emitter cannot be resolved using typical far-field optical microscopy techniques.
      However, by fitting the emission to a model function such as 2-dimensional
      Gaussian, the relative position of the emitter can be determined with precision
      better than 5 nm in a process known as super-resolution imaging. This tutorial
      review describes the basic principles of super-resolution imaging of SERS hot
      spots using single molecules to probe local electromagnetic field enhancements.
      New advances using dipole-based fitting functions and spectrally- and spatially
      resolved measurements are described, providing new insight into SERS hot spots
      and the important roles of both the molecule and the substrate in defining their
      properties. 

PMID- 24309837
TI  - A Dynamical Systems Model for Improving Gestational Weight Gain Behavioral
      Interventions.
AB  - Excessive gestational weight gain (GWG) represents a major public health concern.
      In this paper, we present a dynamical systems model that describes how a
      behavioral intervention can influence weight gain during pregnancy. The model
      relies on the integration of a mechanistic energy balance with a dynamical
      behavioral model. The behavioral model incorporates some well-accepted concepts
      from psychology: the Theory of Planned Behavior (TPB) and the principle of self
      regulation which describes how internal processes within the individual can serve
      to reinforce the positive outcomes of an intervention. A hypothetical case study
      is presented to illustrate the basic workings of the model and demonstrate how
      the proper design of the intervention can counteract natural trends towards
      declines in healthy eating and reduced physical activity during the course of
      pregnancy. The model can be used by behavioral scientists to evaluate decision
      rules for adaptive time-varying behavioral interventions, or as the open-loop
      model for hybrid model predictive control algorithms acting as decision
      frameworks for such interventions.

PMID- 24309838
TI  - Antibiotic and anti-asthmatic drug prescriptions in Italy: geographic patterns
      and socio-economic determinants at the district level.
AB  - PURPOSE: To analyse the prevalence rate of antibiotics and anti-asthmatics in
      children and adolescents at the healthcare district level. METHODS: Data sources
      were three regional prescription databases. A total of 175 healthcare districts
      (3.3 million children/adolescents) participated in the study, providing data for
      the year 2008. Prevalence rate was standardised by age. The ANOVA test was used
      to compare prevalence rates of districts in the three regions. The standardised
      prevalence ratio (SPR) was calculated for each district and a map of the index
      was elaborated. The correlation among latitude, average annual income per
      inhabitant, hospitalisation rate, number of paediatricians per 1,000 resident
      children and prevalence rate was evaluated by district (Spearman's test).
      RESULTS: The antibiotic prevalence rate was, on average, 47.9 % (34.0 to 67.9 %
      between districts), while the anti-asthmatic prevalence was 21.4 % (11.7-35.6 %).
      The prevalence was higher in districts from the southern regions (antibiotics F =
      92.1, anti-asthmatics F = 107.5; p < 0.001). There was a significant correlation
      between the prevalence of antibiotics and anti-asthmatics (rS = 0.77 p < 0.001),
      and the prevalence of both was inversely related to latitude (respectively rS = 
      0.71, -0.72; p < 0.001) and average income (rS = -0.77, -0.73; p < 0.001).
      Children/adolescents living in districts in the lower quintile of average income
      were more exposed to antibiotic (OR = 1.75; 1.74-1.77) and anti-asthmatic (OR
      1.56, 1.55-1.57) prescriptions. CONCLUSIONS: A lower income at the district level
      is related to higher antibiotic and anti-asthmatic drug prescription rates. Local
      socio-economic inequities can concur in prescribing distribution and must be
      considered when planning educational interventions to reduce over-prescription.

PMID- 24309839
TI  - Fingolimod-induced atrioventricular conduction defects in a young lady with
      multiple sclerosis--insights into possible drug mechanism.

PMID- 24309840
TI  - Interspecific attractivity of female sex pheromone components ofPeriplaneta
      americana.
AB  - Female sex pheromones ofPeriplaneta americana, P. australasiae, andBlatta
      orientalis elicit locomotion and upwind orientation in conspecific males.
      Interspecific attraction between these species was observed in a wind tunnel
      assay for most species combinations, with the exception ofP. australasiae males
      not being attracted toP americana females. The role of twoP. americana sex
      pheromone components, periplanone-A (PA) and periplanone-B (PB) in male
      attraction was analyzed. PA induced locomotion in males of all three species,
      with highest threshold concentration inP. americana. PB was effective inP.
      americana andB. orientalis, but not inP. australasiae. Experiments with mixtures
      of both components confirmed an inhibitory influence of PB onP. australasiae
      males when it was added to PA in a ratio of 3?1 or higher. SinceP. americana
      andP. australasiae have been found to be syntopous, and their daily mating
      periods overlap, the female sex pheromone ofP. americana is discussed as an
      isolating factor between both species. 

PMID- 24309841
TI  - Comparison of ponderosa pines as feed and nonfeed trees for abert squirrels.
AB  - Twigs from five ponderosa pine trees (Pinus ponderosa) used by Abert squirrels
      (Sciurus aberti) as feed trees and five nonfeed trees were collected every 45
      days and their monoterpenoid and nutrient content determined. Thet tests
      (unpaired observations) detected no significant difference in the level of
      monoterpenoids in the outer bark of feed (0.77%) and nonfeed (0.75%) trees. The
      same was true for inner bark of feed (0.10%) and nonfeed (0.16%) trees.
      Monoterpenoid levels in outer bark (0.75%) were significantly higher than inner
      bark (0.13%). The inner bark is what is eaten by Abert squirrels. Protein and
      other nutrients did not differ significantly between feed and nonfeed trees.
      However, both outer and inner bark were easier to remove from the woody portion
      of the feed tree twigs than those twigs collected from nonfeed trees. Therefore,
      due to the lack of differences in monoterpenoid and nutrient content between feed
      and nonfeed trees, we attributed the use of certain trees for use as feed trees
      to the ease of peeling and separating outer from inner bark. 

PMID- 24309842
TI  - Identification of sex pheromone components of jack pine budworm,Choristoneura
      pinus pinus freeman.
AB  - Chemical identification and field-trapping experiments have shown that a blend of
      85?15 (E,Z)-11-tetradecenyl acetates and 85?15 (E,Z)-11-tetradecen-1-ols (in a
      9?1 ratio) are female sex pheromone components for jack pine
      budworm,Choristoneura pinus pinus. This blend of chemicals, formulated in PVC
      (0.1 %, w/w) sources is as effective a trap bait as virgin females. Preliminary
      wind tunnel observations have indicated that this blend, effective as a trap
      bait, is not equivalent to females. 

PMID- 24309843
TI  - Some volatile constituents of female dog urine.
AB  - The volatile compounds from female beagle urine, across the state of estrus, were
      examined by headspace gas chromatography and mass spectrometry. The major
      constituents identified were methyl propyl sulfide, methyl butyl sulfide, and
      acetone. Nine minor constituents, including trimethyl amine and five disulfides,
      were identified. Two of the unidentified minor constituents may possibly be
      associated with the state of estrus. 

PMID- 24309844
TI  - Enantiomeric composition of an alarm pheromone component of the antsCrematogaster
      castanea andC. liengmei.
AB  - The enantiomeric composition of 3-octanol produced by the ants,Crematogaster
      castanea Forel andC. liengmei F. Smith, as a component of their alarm pheromone
      complex, has been determined to beS-(+)-3-octanol by gas chromatography of the
      diastereomericS-(+)-3-octanylR-(+)-trans-chrysanthemates. 

PMID- 24309845
TI  - Chemical detection of sex and condition in the crayfishOrconectes virilis.
AB  - Individual crayfish (Orconectes virilis) were tested for responses to water
      containing conspecific individuals of several sex-status categories. Isolated
      males did not react to "self" water but did show aggressive postures while
      isolated, nonself male water was introduced. Males' responses to female water was
      different from responses to male water. Water from aggressing males elicited
      fewer agonistic postures and more "neutral" postures. Females showed little
      difference in response to waters from different categories of conspecifics. 

PMID- 24309846
TI  - Effects of diterpene esters of tigliane, daphnane, ingenane, and lathyrane types
      on pink bollworm,Pectinophora gossypiella saunders (Lepidoptera: Gelechiidae).
AB  - Twenty esters, representing the biogenetically related tigliane, daphnane,
      ingenane, and lathyrane series of diterpenes, were screened for growth-inhibitory
      and insecticidal effects on newly hatched larvae of the North American cotton
      pest,Pectinophora gossypiella (pink bollworm). Among the tigliane derivatives
      tested, only 12-O-tetradecanoylphorbol-13-acetate and 12-O-(2
      methyl)butyrylphorbol-13-decanoate, of seven phorbol diesters isolated from
      croton oil by a new procedure involving droplet countercurrent chromatography,
      were active againstP.gossypiella as both growth inhibitors and insecticides. The
      effects of the former compound were not significantly diminished by acetylation
      of its C-20 primary hydroxy group. Three other croton oil phorbol diester
      constituents, as well as daphnetoxin and daphnetoxin-5,20-diacetate, exhibited
      activity as growth inhibitors, but not as insecticidal agents, at the doses used.
      None of the ingenane or lathyrane derivatives investigated was active in either
      respect. 12-0-Tetradecanoylphorbol-13-acetate was found to cause 100% mortality
      on second-stadium larvae ofCulex pipiens at 0.6 ppm, but exhibited less
      significant effects onOncopeltus fasciatus (second-stadium nymphs) andTribolium
      confusion (adults) when applied at higher doses. 

PMID- 24309847
TI  - Determining pheromone content of hairpencils from individual virgin males
      ofPseudaletia unipuncta (Haw.) (Lepidoptera: Noctuidae).
AB  - Levels of benzaldehyde recovered from virginPseudaletia unipuncta (Haw.) males
      were not influenced by (1) the time hairpencils remained in the solvent (1-72
      hr), (2) anesthetization or agitation of males prior to excision of hairpencils,
      or (3) the time (photophase or scotophase) that hairpencils were excised. Thus
      the interindividual variability observed is not a methodological artifact. Most
      males had similar concentrations in both hairpencils, although in some cases only
      one hairpencil contained pheromone. In one case, a male with partially extruded
      hairpencils had no benzaldehyde at all. Neither pupal weight nor hairpencil
      length proved to be reliable indicators of pheromone content. 

PMID- 24309848
TI  - Attraction of tortricid moths of subfamily olethreutinae to field traps baited
      with dodecadienes.
AB  - All four geometrical isomers of 7,9- and 8,10-dodecadienes with acetate, alcohol,
      and aldehyde functional groups were synthesized and field tested. The field
      survey produced sex attractant lures for 14 insect species. Species in the
      generaCydia, Grapholita, Eucosma, Pelochrista, Petrova, Phenta, Hedya, and
      Pseudosciaphila were captured. Defined lures were developed for some of the
      species captured. Gas chromatographie retention times for all geometrical isomers
      of 7,9- and 8,10-dodecadienes with acetate, alcohol, and aldehyde functional
      groups are reported. A study of the isomerization of 8,10-dodecadienyl acetates
      and aldehydes impregnated in rubber septa is reported. 

PMID- 24309849
TI  - Furocoumarins in shoots ofPituranthos triradiatus (Umbelliferae) as protectants
      against grazing by hyrax (Procaviidea:Procavia capensis syriaca).
AB  - Pituranthos triradiatus (Umbelliferae) in the Negev desert of Israel is rarely
      grazed and when grazing occurs, it is mostly confined to sprouts. It was
      hypothesized that furocoumarins accumulating in the older shoots acted as natural
      protectants against grazing. This was tested using hyrax (Procavia capensis
      syriaca) for bioassay. This diurnally active herbivore is known to be resistant
      to various poisonous plants.Tests were conducted in the autumn (November) and
      summer (June). In November starved hyraxes were offered unlimited amounts of
      thawed, previously frozen old branches ofP. triradiatus. They consumed an average
      amount of 3.4 g dry matter/kg body wt. The animals preferred to stay in the sun,
      and 3-4 hr after feeding, they showed severe photosensitization symptoms: apathy,
      photophobia, and injuries around the eyes and on the back. During the following
      20 hr, four of the five treated animals died. In the second test, the effect of
      old branches, compared with young ones was evaluated in sunlight and under shade.
      Only animals that had eaten old branches and had been left in the sunlight
      developed photosensitization symptoms. Animals offered old shoots consumed
      smaller amounts than those offered young ones. However, they ingested larger
      amounts of imperatorin and isoimperatorin. It is suggested that these two
      furocoumarins induced photosensitization. Under all conditions, the hyraxes ate
      very small amounts of shoots ofPituranthos, compared with the amount of their
      usual diet. This suggests the presence of a severe deterrent factor, possibly
      furocoumarins, in the shoots. Since furocoumarins undergo light-induced cross
      linking with DNA strands, it is conjectured that these natural protectants are
      segregated from regions within the plant where mitosis occurs, and this is why
      young shoots ofPituranthos contain smaller amounts of furocoumarins and are more
      susceptible to various herbivores than are old ones. 

PMID- 24309850
TI  - Possible pheromonal regulation of reproduction in wild carnivores.
AB  - Recent observations of social behavior and reproduction in wolves, coyotes,
      hunting dogs, mongooses, and lions suggest possible involvement of pheromones in
      the regulation of reproductive activity. Observed phenomena resemble the known
      pheromonal effects in mice such as suppression or synchronization of estrus,
      induction of maternal behavior, and interruption of pregnancy. Further studies
      are necessary to verify the supposed biological effects of carnivore pheromones
      and to determine their chemical nature. 

PMID- 24309851
TI  - A multichemical defense mechanism of bitter oliveOlea europaea (oleaceae) : Is
      oleuropein a phytoalexin precursor?
AB  - Olea europaea (Oleaceae) is resistant in nature to insect and microbe attack. Two
      types of chemical protection were found in the foliage. One type is the
      bitterseco-iridoid glycosides oleuropein (1) and ligstroside (2); The other is a
      physical barrier of crystalline oleanolic acid (4) that coats the leaf surface.
      Theseco-iridoid glycosides were isolated using two different countercurrent
      chromatographies: rotation locular countercurrent chromatography (RLCC) and
      droplet countercurrent chromatography (DCCC). The dimethyl ester (III) was shown
      to be an artifact. This is the first isolation of ligstroside fromO. europaea. In
      an antimicrobial test by the paper disk method againstBacillus subtilis,
      Saccharomyces cerevisiae, andEscherichia coli, compounds I, II, and III inhibited
      a growth ofB. subtilis at pH 7. Similar tests under the influence of beta
      glucosidase suggest an aglycone of oleuropein, either the hemiacetal (i) or the
      possible enal-aldehyde (ii), could be the active intermediate. This intermediate
      could be produced rapidly in response to microorganism invasion. Oleuropein
      producing such a postinfection active intermediate could be referred to as a
      phytoalexin precursor. 

PMID- 24309852
TI  - Optimizing outcomes for persons with schizophrenia minimizing adverse effects and
      individualizing treatment.

PMID- 24309853
TI  - Clozapine and tardive movement disorders: a review.
AB  - BACKGROUND: Tardive syndromes (TS) arise from long term exposure to dopamine
      receptor blocking agents. Clozapine has been considered to have low risk of
      causing new onset TS and is considered as a treatment option in patients with TS.
      AIM: This review evaluates the usefulness of clozapine in patients with TS and
      occasional reports of clozapine causing TS. METHODOLOGY: Electronic searches were
      carried out using the search engines of PUBMED, Science direct and Google Scholar
      databases. All reports describing use of clozapine in management of TS,
      monitoring of TS while on clozapine and onset of TS after initiation of clozapine
      were identified. RESULTS: Fifteen trials and 28 case series/case reports describe
      the use of clozapine in TS. Most of these reports show that clozapine is useful
      in patients with TS, in the dose range of 200-300 mg/day and the beneficial
      effect is seen within 4-12 weeks of initiation. One case series and two case
      reports described clozapine withdrawal emergent dyskinesias suggesting a masking
      role of clozapine. One trial, three case series and two case reports describe
      beneficial effects of clozapine on long standing neurological syndromes. There is
      relatively less literature (2 trials and 15 case series/reports) describing the
      emergence of TS with clozapine. CONCLUSION: Evidence of beneficial effects of
      clozapine in TS is greater than its role in causation/worsening of TS. Hence,
      clozapine should be considered in symptomatic patients who develop TS while
      receiving other antipsychotics. Further research on mechanism of TS and clozapine
      effect on TS is required.

PMID- 24309854
TI  - Sleep and borderline personality disorder: a review.
AB  - Sleep problems are very common among psychiatric patients. Borderline personality
      disorder, as a common and severe mental disorder, is associated with different
      types of sleep disturbances, such as disturbances of sleep continuity, altered
      REM sleep regulation and nightmares. These disturbances are the result of
      interaction of the personality traits, concomitant and comorbid diseases and
      environmental factors. Despite the high prevalence of sleep related disorders in
      BPD patients, this aspect of BPD is still neglected in clinical and research
      settings. To date there has been little agreement on sleep characteristics of BPD
      among different studies, and presence of some uncontrolled confounding factors,
      make interpretation of the results difficult. However, it seems that appropriate
      diagnosis and treatment of sleep disorders in BPD patients might lead to better
      outcome. This article aimed to review the current literature of sleep studies in
      BPD. Some recommendations and suggestions were made for future researches in this
      field. 

PMID- 24309855
TI  - Population impact of depression either as a risk factor or consequence of type 2
      diabetes in adults: a meta-analysis of longitudinal studies.
AB  - This meta-analysis examined the reciprocal relationship between depression and
      diabetes mellitus type 2 (T2DM) by conducting a bias adjusted meta-analysis of
      longitudinal studies using relative and absolute risk estimates. Specifically,
      the data were reconstructed to compute relative risk (RR), risk difference (RD),
      and the number needed to be exposed for one additional person to be harmed (NNEH)
      or benefited (NNEB). The 25 studies selected for review generated 29 datasets of
      which 15 examined endpoint A (depression as a risk factor for T2DM), and 14
      examined endpoint B (T2DM as a risk factor for depression). For both endpoints,
      there was a small relative risk increase (for both the RR and hazard ratio (HR))
      though with significant heterogeneity between studies. This however translated to
      a non-significant NNEH of 87 (NNEB 161 to infinity to NNEH 35) and NNEH of 233
      (NNEB 28 to infinity to NNEH 23) for studies examining endpoint A and endpoint B
      respectively. This study suggests that the magnitude of the relative risk
      increase for depression as a risk factor or consequence of T2DM is small without
      significant impact on absolute risk indices. While these risks may be considered
      in terms of individual patient management, they are unlikely to have an impact on
      a population perspective. 

PMID- 24309856
TI  - Homocysteine and serotonin: association with postpartum depression.
AB  - Postpartum depression (PPD) is a disorder of multifactorial origin with
      significant consequences on both maternal and child health. One of the biological
      factors implicated is perturbed methionine-homocysteine metabolism. Since this
      metabolic pathway plays a significant role in myelination of nerve fibers, the
      growth and development of the child would also be adversely affected. We carried
      out this study in 103 women (58 with PPD and 45 without PPD) who delivered their
      child in our institute from December 2010 to November 2011. The study group was
      evaluated for PPD using Edinburgh postnatal depression scale with a cut-off score
      of 10. Assessment of fetal well being was done by APGAR score assessed
      immediately after birth. Serum folic acid, vitamin B12, homocysteine and
      serotonin was done by ELISA. We found significantly elevated levels of
      homocysteine in women with PPD as compared to those without PPD, both at 24-48h
      as well as six weeks after delivery, although no associations were found with
      folate and vitamin B12 levels. Also, there was a significant negative correlation
      between serum homocysteine and serotonin levels in the postpartum depression
      group with a significant negative correlation between homocysteine and serotonin.
      Our study showed a significantly lower APGAR score in the infants born to mothers
      with PPD. Our study also shows that homocysteinemia is associated with PPD
      whether at the first week or sixth week, while low serum serotonin may play a
      role in depression during the first week, but may not have a role in depression
      status at the sixth week. Also, PPD in the mother is related to a low APGAR score
      in infants born to these mothers emphasizing the significance of both mental as
      well as nutritional status of the mother. 

PMID- 24309858
TI  - Attention deficit hyperactivity disorder symptoms reporting in Malaysian
      adolescents: do adolescents, parents and teachers agree with each other?
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a clinical diagnosis relying
      on persistence of symptoms across different settings. Information are gathered
      from different informants including adolescents, parents and teachers. In this
      cross-sectional study involving 410 twelve-year old adolescents, 37 teachers and
      367 parents from seven schools in the Federal Territory of Kuala Lumpur,
      reliability of ADHD symptoms among the various informants were reported. ADHD
      symptoms (i.e. predominantly hyperactive, predominantly inattentive and combined
      symptoms) were assessed by adolescents, teachers and parents, using Conners
      Wells' Adolescent Self-report Scale (CASS), Conner's Teachers Rating Scale (CTRS)
      and Conner's Parents Rating Scale (CPRS) respectively. For predominantly
      hyperactive symptoms, there were statistically significant, weak positive
      correlations between parents and teachers reporting (r=0.241, p<0.01).
      Statistically significant, weak positive correlations were found between
      adolescents and parents for predominantly inattentive symptoms (r=0.283, p<0.01).
      Correlations between adolescents and parents reporting were statistically
      significant but weak (r=0.294, p<0.01). Weak correlations exist between the
      different informants reporting ADHD symptoms among Malaysian adolescents. While
      multiple informant ratings are required to facilitate the diagnosis of ADHD,
      effort should be taken to minimize the disagreement in reporting and better
      utilize the information. 

PMID- 24309857
TI  - Psychiatric morbidity in an urban slum of Mumbai: cross sectional study.
AB  - OBJECTIVE: To find out prevalence of psychiatric morbidity in urban slum
      community in Mumbai. METHODS: A cross-sectional epidemiological study was
      conducted in a health post area of Dharavi, a large slum in Asia. Systematic
      random sampling was employed to select households, the sampling unit in this
      study. All individuals aged 15 and above were eligible to participate in the
      study. Individuals willing to participate were interviewed with symptoms
      checklist - 90 for identifying those with psychiatric illness. All individuals
      identified with a psychiatric disorder on the basis of the symptoms check list
      were invited for a clinical interview conducted by a psychiatrist. Univariate and
      multi-variate analysis was carried out with help of SPSS. RESULTS: The prevalence
      of psychiatric conditions was found to be 12.5%, much higher compared to previous
      studies. Affective disorders were the most common accounting for 42.7% of the
      total morbidity, followed by anxiety disorders (30.7%) and psychoses (21.3%). The
      adjusted odds ratios for psychiatric disorder were significantly higher for
      illiterates and those with primary education only (2.4), unemployed (2.1) and
      those with family history of a psychiatric disorder (1.9). CONCLUSIONS: The high
      prevalence of psychiatric morbidity calls for primary psychiatric services to be
      made available to all and integrated with the primary health care. Family members
      of psychiatric patients constitute high risk group that needs attention in form
      of screening, care and treatment, if necessary.

PMID- 24309859
TI  - Supervision as-usual--is it enough?
AB  - OBJECTIVE: Supervision in most training centers in India happens routinely in all
      training situations and often for a group of trainees rather than in a one to one
      protected manner. How satisfied are trainees with the current methods of
      supervision? How holistic is the supervision? Are there major gaps with this
      method compared to formal individual time protected supervision? These were some
      of the questions that were addressed in this study. METHOD: Satisfaction about
      supervision among 47 post-graduate psychiatry residents in the academic year 2009
      2010 was studied. A checklist was constructed to assess satisfaction in areas of
      educational supervision, clinical supervision and personal/research supervision.
      Two sets of questions were used - one with a likert scale and the other with a
      true/false rating. RESULTS: Psychiatry residents were satisfied with most areas
      of supervision. Clinical supervision was superior to educational (including
      research) and personal supervision. Educational supervision was reported to be
      satisfactory, however, supervision during external postings, examination clinics
      and related to development of specific areas of interest, was inadequate. Low
      levels of satisfaction were reported with supervision regarding psychosocial
      management. In personal supervision, the areas of need identified were: (1)
      Involvement of residents in leisure activities, (2) Social and administrative
      skills and (3) Help in liaison with other disciplines. CONCLUSIONS: Psychiatry
      residents in India were satisfied with most areas of supervision even though it
      is informal and as-usual (i.e. done on a need based way) in most settings. Some
      specific areas may require more formal and time protected supervision.

PMID- 24309860
TI  - Mental health, partner violence and HIV risk among women with protective orders
      against violent partners in Vhembe district, South Africa.
AB  - The aim of this study was to assess mental health, substance use and intimate
      partner violence in relation to Human Immunodeficiency Virus (HIV) risk in South
      Africa. In all 268 women (18 years and older) consecutively receiving a
      protection order in the Vhembe district in South Africa were assessed by an
      external interviewer. Results indicate that 69.8% of the women had never used a
      condom with their abusive partner and 16.4% had been diagnosed with a sexually
      transmitted infection (STI) in the past three months. A high proportion (51.9%)
      had Posttraumatic Stress Disorder (PTSD) and depression (66.4%). In multivariate
      analysis, being married or cohabiting, lower psychological abuse, higher physical
      violence and lower sexual violence, and having a PTSD was associated with never
      using a condom in the past 3 months; higher psychological abuse and higher
      physical and sexual violence were associated with a history of an STI in the past
      3 months. Severity of physical and sexual intimate partner violence and suffering
      from PTSD increased HIV risk calling for multimodal interventions. 

PMID- 24309861
TI  - Internet addiction and its correlates among high school students: a preliminary
      study from Ahmedabad, India.
AB  - PURPOSE: Internet addiction (IA) is an upcoming and less researched entity in
      psychiatry, especially in low and middle income countries. This is the first such
      effort to study IA amongst Indian school students of class 11th and 12th and to
      find its correlation with socio-educational characteristics, internet use
      patterns and psychological variables, namely depression, anxiety and stress.
      METHODS: Six hundred and twenty one students of six English medium schools of
      Ahmedabad participated, of which 552 (88.9%) who completed forms were analyzed.
      Young's Internet Addiction Test and 21 item Depression Anxiety and Stress Scale
      were used to measure IA and psychological variables respectively. Logistic
      regression analysis was applied to find the predictors of IA. RESULTS: Sixty-five
      (11.8%) students had IA; it was predicted by time spent online, usage of social
      networking sites and chat rooms, and also by presence of anxiety and stress. Age,
      gender and self-rated academic performance did not predict IA. There was a strong
      positive correlation between IA and depression, anxiety and stress. CONCLUSIONS:
      IA may be a relevant clinical construct, and needs extensive research even in
      developing nations. All high school students suffering from depression, anxiety
      and stress must be screened for IA, and vice versa.

PMID- 24309862
TI  - Psychiatric morbidity in the Chola royal household.
AB  - This article deals with the presence of hysterical astasia abasia in the father,
      and cyclothymic disturbance in the elder brother of the great Chola emperor and
      builder of the Big Temple at Thanjavur, Raja Raja. 

PMID- 24309863
TI  - Effects of value strains on psychopathology of Chinese rural youths.
AB  - The Strain Theory of Suicide postulates that psychological strains usually
      precede mental disorders including suicidal behavior. This paper focuses on the
      effect of conflicting social value strains on the individual's psychopathology.
      We analyzed the data of 2031 respondents who were proxy informants for suicides
      and community living controls in a large scale psychological autopsy study in
      rural China, with the CES-D depression measure for the psychopathology.
      Individuals having experienced value conflicts between Confucian gender role and
      gender equalitarianism in modern society scored on depression significantly
      higher than the individuals who do not experience the value conflict, and it is
      also true when several other relevant variables were held constant in the
      multiple regression model. This study supports the hypotheses that people who
      confront value conflicts are likely to experience psychopathological strain, and
      the higher the level of strain, the stronger the depression. 

PMID- 24309864
TI  - Dual diagnosis vs. triple diagnosis in HIV: a comparative study to evaluate the
      differences in psychopathology and suicidal risk in HIV positive male subjects.
AB  - INTRODUCTION: The problem of triple diagnosis of HIV, substance abuse and
      psychiatric disorders is a complex one with difficult solutions. HIV disease
      progression is affected by substance use as well as psychiatric illness burden
      due to both direct as well as indirect factors. Continuing substance abuse with
      poor drug adherence coexists with psychiatric disorders leading to increased
      morbidity and mortality. METHOD: A total of 100 HIV positive subjects comprising
      of two groups each having 50 subjects with and without substance abuse were
      assessed using detailed history, mental state examination, WHO schedule for
      clinical assessment in neuropsychiatry (SCAN 2.0) and Beck's Scale for Suicidal
      Ideation (BSS). Statistical analysis used Chi-Square test, Fischer's exact test,
      Student's t-test, Pearson's correlation coefficient, univariate and multiple
      regression analysis, univariate and multiple logistic regression analysis. p
      Value<0.05 was considered to denote statistical significance. RESULTS: Subjects
      with substance use disorder had higher rates of psychiatric morbidity (52% vs.
      24%, 95% CI=0.5200, p<0.05). The rate of antiretroviral therapy default was
      almost double in subjects with substance abuse, as compared to subjects without
      substance use. Suicidal risk was significantly increased (p<0.05) in subjects
      with co-morbid medical disorders but substance abuse did not increase the risk.
      CONCLUSION: Substance abuse inflicts a much greater burden on HIV positive
      individuals as compared to subjects without substance use. Concomitant substance
      abuse resulted in significantly increased duration of illness and psychiatric
      morbidity.

PMID- 24309865
TI  - The explanatory models and coping strategies for alcohol use disorders: an
      exploratory qualitative study from India.
AB  - PURPOSE: The explanatory models (EM) and coping strategies for mental health
      problems influence treatment seeking and the subsequent patient journey. The goal
      of this study was to explore the EMs and coping strategies for alcohol use
      disorders (AUD). METHODS: We conducted semi structured interviews with 29 men
      with AUD and 10 significant others (SO) in two sites in India. Thematic analysis
      was used to analyse data. RESULTS: The former were predominantly married,
      literate and employed; the latter were predominantly wives, literate and
      employed. Alcohol consumption and AUDs are seen to be mainly associated with
      psychosocial stress, with other factors being peer influences, availability of
      disposable income and drinking for pleasure. They are perceived to result in a
      range of adverse impacts on social life, family life, personal health and family
      finances. Various coping strategies were deployed by men with AUD and their
      significant others, for example avoidance, substitution, distraction, religious
      activities, support from AA/friends/family, restricting means to buy alcohol and
      anger management. Reduction/cessation in drinking, improved family relationships,
      improved emotional/physical wellbeing and better occupational functioning were
      the most desired treatment outcomes. CONCLUSION: There are considerable
      similarities, as well as some key differences, observed between the EMs for AUD
      in India and those reported from other cultures which have implications for the
      global applicability and contextual adaptations of evidence based interventions
      for AUD.

PMID- 24309866
TI  - Incidence rates of emotional and behavioural problems in Malaysian children as
      measured by parent ratings of the Strengths and Difficulties Questionnaire.
AB  - BACKGROUND: The aim of this study was to ascertain the rates of emotional and
      behavioural problems (emotional problems, conduct problems, hyperactivity, peer
      problems, and low prosocial behaviour) of Malaysian children. METHODS: In all
      1407 Malaysian parents completed ratings of their children using the Strengths
      and Difficulties Questionnaire. RESULTS: The findings indicating that for these
      emotional and behavioural problems, about 5% are at the abnormal level and that
      another 10% are at the borderline abnormal level. This study also provided
      normative cut-off scores to ascertain borderline and abnormal bands for these
      problems. DISCUSSION: The clinical and cultural implications of the findings are
      discussed.

PMID- 24309867
TI  - Metabolic syndrome among schizophrenia patients: study from a rural community of
      south India.
AB  - Though metabolic syndrome (MS) is a major concern in schizophrenia, there is no
      data among rural community dwelling patients in India. This study describes
      prevalence and correlates of MS in a cohort of schizophrenia patients from a
      rural community of south India. 171 patients with schizophrenia were screened for
      the presence of MS using the International Diabetes Federation (IDF) criteria.
      94.8% were receiving atypical antipsychotics for a mean (SD) duration of 13.04
      (9.51) months. Fifty-four of the 171 (31.6%) patients screened met criterion for
      central obesity. Of these, laboratory results (fasting blood sugar, triglycerides
      and HDL cholesterol) were available for 47 patients. The rest 7 were deemed to
      have met the criteria for MS in order to avoid under-estimation of the syndrome.
      Only 22 (12.86%) patients met the criteria for MS thus defined. Females were
      significantly likely to have both central obesity and MS than males. No other
      predictors of metabolic adverse effects could be identified. Biological and the
      prevailing socio-cultural factors may contribute to such considerably low
      prevalence of metabolic abnormalities. Lack of data from a control group forms
      the most important limitation of this study. 

PMID- 24309868
TI  - Cognitive deficits and its relation with psychopathology and global functioning
      in first episode schizophrenia.
AB  - AIM: The aim was to examine the cognitive deficits profile in first episode
      schizophrenia patients as well as examine the correlation between cognitive
      deficits, psychopathology and global functioning. Better understanding of these
      various facets of this debilitating illness is imperative in planning treatment,
      thereby limiting decline in global functioning. METHODS: Forty-nine schizophrenia
      patients with illness duration less than two years comprised the sample. A
      comprehensive battery of neuropsychological tests, the Positive and Negative
      Syndrome Scale and WHO Disability Assessment schedule were administered to assess
      cognitive functions, psychopathology and global functioning respectively.
      RESULTS: Cognitive deficit quotient for each patient was calculated. In this
      cohort 16.3% of patients had less than 25% of cognitive deficits, 38.8% had 25
      50% of cognitive deficits, 36.7% had 50-75% of cognitive deficits and 8.2% of
      patients had more than 75% cognitive deficits. More than 50% of the patients in
      the present cohort showed deficits in the domains of attention, executive
      functions and learning and memory. Psychopathology significantly correlated with
      global functioning. Negative symptoms significantly correlated with cognitive
      functions of motor speed, attention and executive functions. Step wise linear
      regression analysis showed that duration of illness, attention (sustained
      attention), executive function (response inhibition), negative and positive
      psychopathology predicted level of global functioning at varied levels.
      CONCLUSIONS: Cognitive deficits in multiple domains were observed in the present
      cohort. Attention and executive functions predicted global functioning. There is
      a need for longitudinal studies with larger sample to examine the course of the
      cognitive deficits with progress in illness.

PMID- 24309869
TI  - The efficacy of atomoxetine as adjunctive treatment for co-morbid substance use
      disorders and externalizing symptoms.
AB  - BACKGROUND: We examined the effect of atomoxetine supplementation in treated-as
      usual patients with alcohol, tobacco and other drug dependence (ATOD) and co
      morbid externalizing symptoms (ES). METHOD: Subjects were selected from a
      substance dependence treatment-cohort and assessed for: (a) high ES counts, (b)
      maximum prior period of abstinence, (c) quality of life during that period, and
      (d) shortest time from prior relapse to restarting treatment. Subjects were
      prescribed atomoxetine and followed up to their first relapse. RESULTS: Out of
      262 subjects screened during the study period (March-April 2008), 18 subjects who
      fulfilled eligibility criteria were recruited. All subjects were male, with early
      onset of substance dependence to at least two substances. Atomoxetine treatment
      led to significant treatment benefits: ES reduction, longer abstinence, shorter
      turnaround time and better quality of life. CONCLUSIONS: Atomoxetine has a
      potential role in the treatment of early onset ATOD patients with ES, as an
      adjuvant to the standard treatment.

PMID- 24309870
TI  - Suicidal behaviour in the ancient Greek and Roman world.
AB  - OBJECTIVE: We attempt to present and analyze suicidal behaviour in the ancient
      Greek and Roman world. METHODS: Drawing information from ancient Greek and Latin
      sources (History, Philosophy, Medicine, Literature, Visual Arts) we aim to point
      out psychological and social aspects of suicidal behaviour in antiquity. RESULTS:
      The shocking exposition of suicides reveals the zeitgeist of each era and
      illustrates the prevailing concepts. Social and legal reactions appear
      ambivalent, as they can oscillate from acceptance and interpretation of the act
      to punishment. In the history of these attitudes, we can observe continuities and
      breaches, reserving a special place in cases of mental disease. The delayed
      emergence of a generally accepted term for the voluntary exit from life (the term
      suicidium established during the 17th century), is connected to reactions
      triggered by the act of suicide than to the frequency and the extent of the
      phenomenon. CONCLUSIONS: The social environment of the person, who voluntary ends
      his life usually dictates the behaviour and historical evidence confirms the
      phenomenon.

PMID- 24309871
TI  - Seroprevalence of human immunodeficiency virus, hepatitis B surface antigen, and
      hepatitis C in substance dependents admitted in a tertiary hospital at Amritsar,
      India.
AB  - Substance dependents often seek help for deaddiction and are detected positive
      during routine viral markers testing. We screened such patients in our hospital
      ShriGuru RamDas Institute of Medical Sciences and Research (SGRDIMSR) which is
      situated in a rural area adjoining the city of Amritsar; being a tertiary care
      centre it caters to a large population. A total of 1382 patients were admitted to
      the psychiatry ward from 01 July 2009 to 31 December 2012 and screened for study,
      out of whom 4.63% (n=64) refused to consent for participation in the study. Out
      of 1318 screened participants, 85.96% (n=1133) had opioid dependence, followed by
      tobacco (61.68%), alcohol (23.97%), cannabis (0.04%), and other substances
      (0.01%) including benzodiazepine, inhalants, etc. Out of 118 seropositive
      injection drug users (IDUs), 66.10% (n=78) patients were Hepatitis C positive,
      15.25% (n=18) were detected as HIV reactive and 5.08% (n=6) patients were found
      to be HBsAg positive. This is significant as HCV is mostly overlooked in
      government health policies and overshadowed by HIV. Our study also emphasises the
      need for HCV screening along with HIV in various health programmes. Our study is
      important as it may help in reviewing health policies as HIV infection among IDUs
      is highest (30.40%) in this part of the country as per data by UNAIDS (National
      AIDS Control Organisation, 2010) and there is no comprehensive policy for
      Hepatitis B and C like that of HIV. 

PMID- 24309872
TI  - Clinical characteristics of aggression in children and adolescents admitted to a
      tertiary care centre.
AB  - BACKGROUND AND NEED FOR THE STUDY: Identification and management of aggression is
      a major mental health priority in hospitalised patients. However, no such studies
      have been done in child and adolescent in-patients in India. OBJECTIVES: To study
      the clinical and demographic features; characteristics of the aggression and
      methods employed to manage aggression in child and adolescent in-patients.
      MATERIALS AND METHODS: Child and adolescent in-patients between the ages of 4 and
      16 years who were aggressive were included. The tools used were the MINI
      International Neuropsychiatric Interview (M.I.N.I) KID, Overt Aggression Scale
      (OAS), Children's Global Assessment Scale (CGAS), and a Semi-structured interview
      regarding each aggressive episode. RESULTS: 31 patients displayed aggressive
      behaviour out of the 131 patients who were admitted during the study period.
      Aggressive acts were more common in males, those with academic difficulties, who
      had a past history of aggression, with suicidal ideation or suicidal attempts.
      Aggression occurred across diagnostic categories but a significant proportion was
      diagnosed to have Disruptive Behaviour Disorders either as a primary diagnosis or
      as comorbidity. 90.6% were on psychotropic medication prior to admission. Around
      2/3rd of aggressive episodes occurred in the evening and family members (85.7%)
      were the most common targets of aggression. CONCLUSION: There are a few factors
      that can possibly help identify and predict aggression in children and
      adolescents in a hospital setting. More research is required to understand
      aggression in clinical settings.

PMID- 24309873
TI  - Clinical and neuropsychiatric status in children with Williams-Beuren Syndrome in
      Upper Egypt.
AB  - The aim of this study was to evaluate and explore the clinical, neuropsychiatric
      status and EEG pattern in a series of children with Williams-Beuren syndrome
      (WBS) in Assiut, Upper Egypt. We aimed to provide a comprehensive data comparable
      to what has been published, to enable us to make comparisons across different
      cultural areas. This will contribute to a better definition of the
      neuropsychiatric features that may be specific to WBS that allows early and
      better detection and management of those children. MATERIALS AND METHODS: A
      series of 17 WBS children patients who consulted at our hospital were evaluated.
      The patients were assessed mainly for clinical, neurological, psychiatric and EEG
      status. We performed FISH for all patients. RESULTS: All patients had a deletion
      of the long arm of chromosome 7 (7q 11.23). All had elfin facies. Neurological
      examination revealed hypotonia in 25% of patients and rigidity (12.50%), brisk
      deep tendon reflexes (25%), abnormal plantar response (12.50%). Cerebellar and
      extrapyramidal signs were frequent: dysmetria (31.25%), dysdiadochokinesia
      (31.25%) and ataxia (18.75%). Epileptic seizures were present in 31.25% of
      patients and ADHD (37.5%). Autism was present in one patient. EEG abnormalities
      were present in 31.25%. Congenital cardiopathies were present in 62.50%.
      CONCLUSION: Our data showed that WBS children had multi-systemic clinical
      complications and the management of those patients requires the pediatrician to
      understand the natural course of this condition, awareness of potential medical
      problems, and periodic baseline clinical, neuropsychiatric evaluations,
      monitoring, and rapid intervention to improve the medical care for patients who
      have WBS.

PMID- 24309874
TI  - Djinnati syndrome: symptoms and prevalence in rural population of Baluchistan
      (southeast of Iran).
AB  - OBJECTIVE: The present study describes "Djinnati," a culture-bound syndrome and
      examines its prevalence and demographic attributes such as age, gender and
      education level in the rural population of Baluchistan in southeast Iran. METHOD:
      In this cross-sectional study, the participants (n=4129) were recruited from
      people living in rural areas of Baluchistan (southeast Iran) by multistage
      sampling. The data were collected through interviews with local healers, health
      care personnel, family health records, interview patients suspected with the
      disorder and their relatives. We administered the dissociative experiences scale.
      RESULTS: Prevalence of Djinnati syndrome was about 0.5% in the studied population
      and 1.03% in women. All patients who experienced episodic symptoms of Djinnati
      were female. The most common reported symptoms were altered consciousness and
      memory, muteness, laughing, crying, incomprehensible speech and hallucination
      that have been attributed to a foreign entity called "Djinn." In addition loss of
      speech or change in speech rhythm and tone of voice was observed in a subgroup.
      In one case, speaking in a different language during the attack was reported.
      There was partial and rarely complete amnesia during the attack. Attacks usually
      lasted from 30 min to 2h. DISCUSSION: It is suggested that future studies explore
      prevalence of Djinnati syndrome in women and explore predisposing, precipitating,
      and maintaining factors. It is further suggested that a comprehensive pathology
      model should integrate the data related to socio-cultural context in order to
      prevent and treat this syndrome.

PMID- 24309875
TI  - The relationship between attachment styles and alexithymia: mediating role of
      defense mechanisms.
AB  - This study examined the mediating role of ego defense mechanisms on the
      relationship between attachment styles and alexithymia. Four hundred and forty
      three Iranian high school students (213 boys, 230 girls) participated in this
      study. Participants completed Defense Styles Questionnaire (DSQ-40), Adult
      Attachment Inventory (AAI), and Farsi version of the Toronto Alexithymia Scale
      (FTAS-20). Results showed a significant negative correlation between secure
      attachment style and alexithymia, while avoidant and ambivalent attachment styles
      showed significant positive associations with alexithymia. Regression analysis
      indicated that defense mechanisms have a mediating role between attachment styles
      and alexithymia. It can be concluded that a mediation role of ego defense
      mechanisms on the relationship between attachment styles and alexithymia was
      partial. 

PMID- 24309876
TI  - Relationship between anhedonia and impulsivity in schizophrenia, major depression
      and schizoaffective disorder.
AB  - BACKGROUND: Anhedonia and impulsivity are prominent symptoms of many psychiatric
      disorders and may indicate worse prognosis, notably in schizophrenia and major
      depression. Despite the convergence of negative outcomes from both dimensions,
      the relationship between anhedonia and impulsivity in psychiatric disorders has
      been seldom directly assessed. The objective of the present study is to examine
      the correlations between anhedonia and impulsivity in three diagnostic groups:
      major depression, schizophrenia and schizoaffective disorder. SAMPLING AND
      METHODS: 121 outpatients (Mansoura University Hospital, Egypt) with major
      depressive disorder (N=29), schizophrenia (N=59), and schizoaffective disorder
      (N=33), were assessed and responded to the Beck Depression Inventory, Barrat's
      Impulsivity Scale-11, and Chapman's Social and Physical Anhedonia Scales.
      RESULTS: Physical and social anhedonia scores were negatively correlated to
      impulsivity scores in major depression patients. Conversely, higher scores in
      physical and social anhedonia predicted higher impulsivity scores in
      schizophrenia. No correlations between impulsivity and anhedonia were evidenced
      among schizoaffectives. CONCLUSION: The relationship between self-reported
      physical and social anhedonia and impulsivity is diagnosis-specific.

PMID- 24309878
TI  - Implications of spiritual experiences to the understanding of mind-brain
      relationship.
AB  - OBJECTIVE: While there has been a large increase in scientific studies on
      spirituality, there has been too few of studies of the core of spirituality:
      spiritual experiences (SE), which often involve altered states of consciousness,
      reports of anomalous experiences and of consciousness beyond the body. This paper
      argues that SE, although usually neglected in debates regarding mind-brain
      relationship (MBR), may provide the much needed enlargement of the empirical
      basis for advancing the understanding of the MBR. METHODS: This paper briefly
      presents and discusses recent scientific investigations on some types of SE
      (meditative states, end of life and near death experiences, mediumship and
      alleged memories of previous lives) and their implications to MBR. RESULTS:
      Neurofunctional studies of SE have shown that they are related to but not
      necessarily caused by complex functional patterns in several brain areas. The
      study of meditative states, as voluntarily induced mind states that influence
      brain states has been a privileged venue to investigate top-down (mind over
      brain) causation. End of life and near death experiences offer cases of
      unexpected adequate mental function under severe brain damage and/or dysfunction.
      Scientific investigations of several types of SE have provided evidence against
      materialistic reductionist views of mind. CONCLUSIONS: The recent trend to
      scientifically investigate SE has already produced interesting and thought
      provoking findings that deserve careful further exploration. Because of their
      potential implication, these findings may also contribute to the understanding of
      MBR, which remains an important, yet poorly explored way to investigate human
      nature.

PMID- 24309877
TI  - A Hindi version of the Composite Scale of Morningness.
AB  - BACKGROUND: Several pen and paper measures of human circadian preference are
      available in English, but none are available in Hindi, hampering research in
      circadian behavior among Hindi speaking populations in India and elsewhere. The
      present study describes a Hindi version of the Composite Scale of Morningness
      (CSM), a self-reported questionnaire widely used to assess
      morningness/eveningness (M/E). M/E has been used a proxy for circadian phase in
      lieu of cumbersome and expensive laboratory studies. METHOD: The thirteen item
      English version of the CSM was translated into Hindi and independently back
      translated into English. Inconsistencies between the original and back translated
      versions were then resolved. Both versions were next administered to bilingual
      persons at Delhi, India (N=130). After intra-class correlations between the Hindi
      and the English versions were examined, the Hindi version was administered to
      community based participants representing different age groups (N=310). RESULTS:
      There was satisfactory intra-class correlation (ICC) between the total scores for
      the Hindi and the English versions of the CSM (Cronbach's alpha=0.873), with
      variation for individual items scores. Total CSM scores in the second sample
      suggested a significant association with age, consistent with published reports
      with the English CSM, i.e., morningness tendencies were more likely to be
      reported by older adults. Significant associations with gender or educational
      status were not observed. CONCLUSIONS: The Hindi CSM is a brief questionnaire
      that provides behavioral measures of diurnal preference. It is freely available
      for research in Hindi speaking populations.

PMID- 24309879
TI  - Psychiatry, religion, positive emotions and spirituality.
AB  - This paper proposes that eight positive emotions: awe, love/attachment,
      trust/faith, compassion, gratitude, forgiveness, joy and hope constitute what we
      mean by spirituality. These emotions have been grossly ignored by psychiatry. The
      two sciences that I shall employ to demonstrate this definition of spirituality
      will be ethology and neuroscience. They are both very new. I will argue that
      spirituality is not about ideas, sacred texts and theology. Rather, spirituality
      is all about emotion and social connection that are more dependent on the limbic
      system than the cortex. Specific religions, for all their limitations, are often
      the portal through which positive emotions are brought into conscious attention.
      Neither Freud nor psychiatric textbooks ever mention emotions like joy and
      gratitude. Hymns and psalms give these emotions pride of place. Our whole concept
      of psychotherapy might change, if clinicians set about enhancing positive
      emotions, rather than focusing only on the negative ones. 

PMID- 24309880
TI  - Obsessions from the past: a study of the chapter on "blasphemous thoughts" in
      "The Ladder of Divine Ascent" (7th century AD).
AB  - In this study, we examine the similarities and the differences between obsessions
      and the phenomena described in religious language as "blasphemous thoughts". The
      basis of our study is an ascetic text of the 7th century AD, entitled "The Ladder
      of Divine Ascent", written by Saint John Climacus (ca. 579-649), abbot of St.
      Catherine Monastery, Sinai. The book is considered to be one of the fundamental
      sources of monastic literature, which has influenced Christian anthropology.
      Research on the "Ladder" gives an insight in where the religious and the
      psychiatric pathogenic, diagnostic and therapeutic approaches converge or
      diverge. In addition to the scientific value, the data derived from the research
      could be useful to the therapist, especially when he/she copes with religious
      patients, in order to acquire a better empathy and thus lesser the patient's
      resistance toward therapy. 

PMID- 24309882
TI  - A synopsis of recent influential papers published in psychiatric journals from
      the Arab world (2012).
AB  - This review includes six recent and influential papers that have appeared in the
      three leading psychiatry journals from the Arab region. The first paper examined
      the role of personality profile in the motivation to quit smoking and concluded
      that there is a positive correlation between Novelty seeking (NS), Persistence
      (P), Cooperativeness (C) and motivation to quit smoking. The second study
      discussed the prevalence of abuse history in patients with schizophrenia whether
      physical or sexual, and its impact on their condition and function. The third
      paper reported that patients with substance abuse problem show more risky sexual
      behaviors than normal controls. The fourth study high-lighted the similarities
      regarding complaints about sleep and polysomnographic changes in depression
      patients and somatoform disorder patients. The fifth paper, investigated the
      prenatal and perinatal risk factors in autistic disorders. The sixth and final
      article concluded that poor levels of maternal fetal attachment during the course
      of pregnancy should be managed in order to optimize fetal and maternal health.
      Overall, the papers describe a wide spectrum of research initiatives in the Arab
      world that are likely to have implications for global mental health. 

PMID- 24309881
TI  - Mental health service use from a religious or spiritual advisor among Asian
      Americans.
AB  - BACKGROUND: Asian Americans experience significant underuse of mental health
      treatment. Religious clergy and spiritual advisors play a critical role in
      delivering mental health care in the United States. Limited knowledge exists
      about their use among Asian Americans. OBJECTIVE: We describe mental health
      service use from a religious/spiritual advisor among Asian Americans. METHODS: We
      analyzed data from 2095 respondents in the 2002-2003 National Latino and Asian
      American Study. RESULTS: Lifetime and 12-month prevalence of mental health
      service use from a religious/spiritual advisor (5.5% and 1% overall,
      respectively) was generally higher among U.S.-born Asians and those with a 12
      month mental disorder (23.6% and 7.5%, respectively). Religious/spiritual
      advisors were seen by 35% of treatment-seeking Asian Americans with a lifetime
      mental disorder. They were seen as commonly as psychiatrists but less commonly
      than a mental health specialist or general medical provider. Approximately 70% of
      those seeking treatment had a mental disorder, significant proportions of whom
      sought treatment in the absence of a psychiatrist, a mental health specialist or
      even a healthcare provider. A significant majority with 12-month use perceived
      the care as helpful, felt accepted/understood and satisfied (71-86%). However,
      only 31% rated the care as excellent, 28% quit completing care, and referral
      rates for specialty mental health treatment were low, even among those with a
      mental disorder (9.5%). CONCLUSIONS: Religious/spiritual advisors are a key
      source of treatment-seeking for Asian Americans with a mental disorder. Quality
      of care and low referral rates for specialty mental health treatment warrant
      further attention and need for increased collaboration with the mental health
      system.

PMID- 24309883
TI  - Gender and somatoform disorders: do subtypes of somatoform disorders differ?

PMID- 24309884
TI  - Neurocysticercosis presenting as acute psychosis: a rare case report from rural
      India.
AB  - Neurocysticercosis, caused by the larval stage of the tapeworm Taenia solium, is
      the most common parasitic infection of the central nervous system. Its clinical
      manifestations are varied, non specific and pleomorphic, depending on multiple
      factors. Seizures are the commonest presentation of neurocysticercosis. In this
      communication we describe an interesting case of multiple neurocysticercosis in a
      young presenting with psychiatric manifestations. He responded well to steroid
      and antipsychotic treatment. This case highlights an uncommon presentation of
      neurocysticercosis and significance of early recognizing this reversible cause
      will avoid delay in treatment. 

PMID- 24309885
TI  - High frequency TMS for the management of Borderline Personality Disorder: a case
      report.
AB  - OBJECTIVE: To assess the effect of repetitive trans-cranial magnetic stimulation
      (rTMS) therapy in the management of Borderline Personality Disorder (BPD).
      METHOD: The subject was a 22 years old girl. She was first diagnosed with BPD
      after one of her suicidal attempts about two years ago. She received 10 sessions
      of high-frequency TMS over her left dorsolateral prefrontal cortex. Assessment
      was done before treatment, exactly after the last session, one and three months
      after treatment. Functional Scanning was performed before and after the TMS
      sessions and one month after the last session. RESULTS: Results of block design
      analysis revealed increased activity in amygdala, Superior Temporal Gyrus,
      Superior Frontal Gyrus, Middle Frontal Gyrus and parahippocampus in negative
      neutral and negative-rest contrasts. In contrast to the mentioned areas that
      exhibited decrease in activity after treatment, we found that middle temporal
      gyrus and post central gyrus were activated by the emotional stimuli. The changes
      in brain activity were associated with decrease in BPD severity (measured by BPD
      severity index) and depression and impulsivity level. CONCLUSION: Regardless of
      the limitations of this study, our findings suggest a positive role for rTMS in
      the management of BPD.

PMID- 24309886
TI  - Psychiatry in Pakistan: focus on child mental health.

PMID- 24309887
TI  - Lorazepam withdrawal catatonia: a case report.
AB  - Catatonia is a rare manifestation of benzodiazepine withdrawal in elderly
      patients who have used it for a long time. We present a case of lorazepam
      withdrawal catatonia and highlight issues in diagnosis and management. 

PMID- 24309888
TI  - The prevalence and correlates of guilt in depression: a study from North India.

PMID- 24309889
TI  - Cryptococcal meningitis presenting as acute psychosis in a HIV positive patient.

PMID- 24309890
TI  - Mobile clinic services for opioid users: a feasible treatment modality.

PMID- 24309891
TI  - Inter-rater agreement of the Operationalized Predicaments of Suicide (OPS).

PMID- 24309892
TI  - Folie a deux mixed dissociative disorder--a case report.

PMID- 24309893
TI  - The case of a 43-year old Turkish male patient with Nasu-Hakola disease.

PMID- 24309894
TI  - Pediatric autoimmune neuropsychiatric disorders with streptococcus infection: a
      case report from India.

PMID- 24309895
TI  - The ball is in your (journal editor's) court: newer insights into the ethics &
      'un'-ethics in publishing.

PMID- 24309896
TI  - Association of atherosclerosis-related markers and its relationship to n-3
      polyunsaturated fatty acids levels with a prevalence of coronary artery disease
      in an urban area in Japan.
AB  - Higher intakes of fish and n-3 polyunsaturated fatty acids (n-3PUFAs:
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) are associated with a
      reduced risk of coronary artery disease (CAD). We investigated the relationships
      between fish-derived n-3PUFAs and prevalence of CAD, and to assess the
      association of n-3PUFAs with atherosclerosis-related markers in an urban area.
      This study was designed as a hospital-based cross-sectional study on 649
      consecutive outpatients who had undergone regular examinations between April 2009
      and October 2009. After adjustments for the coronary risk factors in a
      multilogistic regression analysis of variables for which a significant difference
      was identified between the group of patients with a prevalence of CAD and the
      group with no prevalence of CAD, the multivariable odds ratio (95 % confidence
      interval) was 0.394 (0.205/0.760; P = 0.005) for the highest (92.4-373.5 MUg/ml)
      versus lowest (6.2-40.0 MUg/ml) quartile of serum EPA values and 0.433
      (0.228/0.824; P = 0.011) for the highest (160.7-451.8 MUg/ml) versus lowest (35.7
      100.7 MUg/ml) quartile of serum DHA values. Multivariate regression analyses
      after adjustment for risk factors showed that higher serum EPA and DHA levels
      were independent variables of a higher level of serum apolipoprotein A-1, a major
      compound of high-density lipoprotein. However, the results suggested that there
      might be conflicting effects of EPA and DHA in regard of the serum levels of
      other lipid markers. This cross-sectional study suggests that higher serum levels
      of n-3PUFAs were associated with a lower prevalence of CAD and an increase in
      serum apolipoprotein A-1 level, even in an urban area.

PMID- 24309897
TI  - Association of intramural fat deposition in the interatrial septum with focal
      atrial tachyarrhythmias originating near the atrioventricular node.
AB  - We describe a case with three focal atrial tachycardias (ATs) and focal atrial
      fibrillation (AF) originating from the interatrial septum (IAS) near the
      atrioventricular node (AVN). Contrast-enhanced computed tomography demonstrated
      the association of fat deposition within the anterior IAS near the AVN with
      successful ablation sites of these ATs and AF. This is the first report that the
      intramural fat deposition in the IAS could be associated with the formation of AT
      and AF re-entry circuits originating near the AVN. 

PMID- 24309899
TI  - Immunoelectrophoretic analysis of seed proteins from Pisum sativum L.
AB  - Soluble proteins of pea seed were investigated by quantitative immunological
      methods. Vicilin, legumin, pea seed lectin (PEA), 26 albumins and a globulin (B1)
      were detected and observed during seed development, germination and under
      different extraction and fractionation procedures. Vicilin and legumin were found
      to be immunologically distinctly different. Legumin was found to be comprised of
      two similar proteins, Legumin species I and II. Vicilin, but no legumin, was
      detected in the embryonic axis.Three albumins, B1 and PEA were found to be
      synthesized after the onset of legumin synthesis.Among the pea lines
      investigated, one line exhibited distinct differences with respect to the
      albumins and PEA.Some observations indicate that PEA might interact with other
      seed proteins of pea. 

PMID- 24309898
TI  - Analysis of the human tissue-specific expression by genome-wide integration of
      transcriptomics and antibody-based proteomics.
AB  - Global classification of the human proteins with regards to spatial expression
      patterns across organs and tissues is important for studies of human biology and
      disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to
      classify the tissue-specific expression of genes across a representative set of
      all major human organs and tissues and combined this analysis with antibody-based
      profiling of the same tissues. To present the data, we launch a new version of
      the Human Protein Atlas that integrates RNA and protein expression data
      corresponding to ~80% of the human protein-coding genes with access to the
      primary data for both the RNA and the protein analysis on an individual gene
      level. We present a classification of all human protein-coding genes with regards
      to tissue-specificity and spatial expression pattern. The integrative human
      expression map can be used as a starting point to explore the molecular
      constituents of the human body. 

PMID- 24309900
TI  - Investigations on the transfer of isolated nuclei into plant protoplasts.
AB  - Nuclei were isolated from various types of donor protoplasts and were transferred
      into receptor protoplasts in numerous combinations. Five percent uptake was
      achieved under conditions which did not interfere with viability and subsequent
      culture of receptor protoplasts. Methodological investigations on nuclei uptake
      were carried out with cereal and tobacco protoplasts. To look for biological
      proof of integration and replication of transferred nuclear genes, two
      complementing, chlorophyll-deficient, light-sensitive mutants of tobacco were
      used as sources of nuclei and receptor protoplasts. Ca. 5.5 * 10(7) receptor
      protoplasts were cultured following transplantation experiments involving these
      complementing mutants and about 1.8 * 10(7) of the resulting calli were subjected
      to selective conditions which discriminate against the parental types. No nuclear
      hybrids were detected, although in control experiments somatic hybrids were
      obtained by protoplast fusion. Some explanations for failure of nuclear hybrid
      formation are discussed together with other possible approaches for selective
      somatic combination of plant cell genophores. 

PMID- 24309901
TI  - The causes of genetic male sterility in 3 soybaen lines.
AB  - The cause of male sterility in 3 soybean lines, TGM 103-1, N-69-2774 and TGM 242
      4 was studied. In TGM 103-1, which was both male and female sterile, two
      different abnormalities were associated with sterility. Precocious movement of a
      few chromosomes at the metaphase I stage resulted into the production of non
      functional pollen while cells which underwent apparent normal meiotic division
      had disintergration of the tapetal cell wall immediately after the free
      microspore stage leading to the starvation and subsequent death of the developing
      microspores. In lines N-69-2774 and TGM 242-4, both of which were partially
      sterile, male sterility resulted from a failure of cytokinesis after the
      telophase II stage. Meiosis proceeded normally but the 4 microspores after
      telophase II failed to separate into pollen grains and degenerated thereafter. 

PMID- 24309902
TI  - Introduction of two chromosomal translocations of Sus scrofa nigripes and Sus
      scrofa scrofa into the genome of Sus scrofa domestica.
AB  - Hybrids between wild and domestic pigs with two types of translocations in the
      karyotype were studied. The translocations of type I were first detected in a
      population of the Middle Asian wild boars. Type II was identified in a
      populations of the Central European subspecies. A large number of Middle Asian
      and Central European hybrids and their F1-F3 hybrids from crosses with domestic
      pigs were viable. By means of differential chromosome staining, the mechanism of
      the formation of 'synthetic' karyotypes, as well as some features of
      translocation inheritance, were established.The introduction of two
      translocations into a single genome and the same chromosome set of these hybrids
      not only modified chromosome number, but also the composition of the linkage
      groups. The hybrids heterozygous for two translocations and their hybrid progeny
      are characterized by an obligatory heterozygozity for a large number of genes,
      gene complexes and linked genes. It is suggested that this heterozygozity may be
      associated with heterotic events. The use of such hybrids in pig breeding may
      provide heterosis for viability and productivity. 

PMID- 24309903
TI  - Genetics of tassel branch number in maize and its implications for a selection
      program for small tassel size.
AB  - Tassel branch numbers of six crosses of maize (Zea mays L.) were analyzed to
      determine inheritance of this trait. Generation mean analyses were used to
      estimate genetic effects, and additive and nonadditive components of variance
      were calculated and evaluated for bias due to linkage. Both narrow-sense and
      broad-sense heritabilities were estimated. Additive genetic variance estimates
      were significant in five of the six crosses, whereas estimates of variance due to
      nonadditive components were significant in only three crosses. Additionally,
      estimates of additive variance components usually were larger than corresponding
      nonadditive components. There was no evidence for linkage bias in these
      estimates. Estimates of additive genetic effects were significant in four of six
      crosses, but significant dominance, additive * additive and additive * dominance
      effects also were detected. Additive, dominance, and epistatic gene action,
      therefore, all influenced the inheritance of tassel branch number, but additive
      gene action was most important. Both narrow-sense and broadsense heritability
      estimates were larger than those reported for other physiological traits of maize
      and corroborated conclusions concerning the importance of additive gene action
      inferred from analyses of genetic effects and variances. We concluded that
      selection for smalltasseled inbreds could be accomplished most easily through a
      mass-selection and/or pedigree-selection system. Production of a small-tasseled
      hybrid would require crossing of two small-tasseled inbreds. We proposed two
      genetic models to explain unexpected results obtained for two crosses. One model
      involved five interacting loci and the other employed two loci displaying only
      additive and additive * additive gene action. 

PMID- 24309904
TI  - Genetics of speciation in the basidiomycetous genus Polyporus.
AB  - The wood rotting basidiomycete Polyporus (subgenus Leucopori Quel.) was chosen in
      order to investigate by genetic parameters the validity of the classical species
      concept based on typological characters.Species deliminations in this genus are
      derived from morphological characters and depend mainly on the size of hymenial
      pores. They were compared with those assigned from mating relations between 26
      races of different geographic origin.All races could unequivocally be grouped
      into three separate entities corresponding with the typological species P.
      arcularius, P. brumalis and P. ciliatus on the basis of the following results: 1.
      As expected, the basic breeding system in Polyporus is the tetrapolar mechanism
      of homogenic incompatibility controlled by multiple alleles of the mating type
      factors A and B. 2. All intraspecific combinations were fertile. A conspicuous
      barrage formed in those crosses where dikaryotization and fruiting were impaired.
      This barrage is characterized by a clear zone, about 1-2 mm wide, free of aerial
      hyphae and reduced hyphal density in the growth medium. The delay observed in the
      onset of the sexual cycle was caused by retarded fusion of hyphae and blocked
      exchange of nuclei despite a compatible combination of the mating types. 3. Using
      two races of P. ciliatus as an example, it was revealed that barrage formation is
      started by the specific interaction of three independent genes (bi (+)/bi =
      barrage initiation, bfI 1/bfI 2 and bfII 1/bfII 2 = barrage formation) in a way
      characteristic for systems of heterogenic incompatibility: barrage formation
      requires the presence of the allele bi (+) in at least one mating partner
      additional to a heterogeneity in both bf-genes. 4. Interspecific combinations
      were sterile. There is no hyphal fusion between the mating partners and because
      of the mutual repulsion a sharp line formed in the area of contact that was
      designated as border line. Its formation is independent of mating type or nuclear
      status of the confronted mycelia. The good correspondence of the species limits
      derived from morphological and genetic data indicates the applicability and
      validity of both the typological and the biological species concept. The latter,
      however, proved superior in compensating the variability of morphological
      characters, at least in higher fungi.The bearing of our results and other known
      control mechanisms of the sexual cycle on the definition of the category
      'species' are integrated in a proposed modification of the biological species
      concept: populations (races) belong to different species when the failure to
      interbreed and to produce viable offspring is not caused by genetic parameters
      operating in completion of the sexual cycle. 

PMID- 24309906
TI  - GM2 gangliosidosis in British Jacob sheep.
AB  - GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old
      pedigree Jacob lambs from two unrelated flocks presenting clinically with
      progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical
      signs included hindlimb ataxia and weakness, recumbency and proprioceptive
      defects. Histopathological examination of the nervous system identified extensive
      neuronal cytoplasmic accumulation of material that stained with periodic acid-
      Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic
      bodies within the nervous system. Serum biochemistry detected a marked decrease
      in hexosaminidase A activity in the one lamb tested, when compared with the
      concentration in age matched controls and genetic analysis identified a mutation
      in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep
      in North America. The identification of Tay-Sachs disease in British Jacob sheep
      supports previous evidence that the mutation in North American Jacob sheep
      originated from imported UK stock.

PMID- 24309905
TI  - Lisdexamfetamine dimesylate augmentation in adults with persistent executive
      dysfunction after partial or full remission of major depressive disorder.
AB  - Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant
      monotherapy for executive dysfunction in partially or fully remitted major
      depressive disorder (MDD). This randomized, placebo-controlled study
      (NCT00985725) enrolled 143 adults (18-55 years) with mild MDD (Montgomery-Asberg
      Depression Rating Scale (MADRS) score <= 18) and executive dysfunction (Behavior
      Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global
      Executive Composite (GEC) T score >= 60) on stable antidepressant monotherapy for
      >= 8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks
      of double-blind LDX (20-70 mg/day) or placebo augmentation, followed by 2 weeks
      of single-blind placebo. The primary end point was change from baseline to week
      9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments
      included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse
      events (TEAEs). Of 143 randomized participants, 119 completed double-blind
      treatment (placebo, n=59; LDX, n=60). Mean +/- standard deviation (SD) BRIEF-A
      GEC T scores decreased from baseline (placebo, 74.2 +/- 8.88; LDX, 76.8 +/- 9.66)
      to week 9/EOS (placebo, 61.4 +/- 14.61; LDX, 55.2 +/- 16.15); the LS mean (95%
      CI) treatment difference significantly favored LDX (-8.0 (-12.7, -3.3);
      P=0.0009). The LS mean (95% CI) treatment difference for MADRS total score also
      significantly favored LDX (-1.9 (-3.7, 0.0); P=0.0465). TEAE rates were 73.6%
      with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this
      trial, LDX augmentation significantly improved executive dysfunction and
      depressive symptoms in participants with mild MDD. The safety profile of LDX was
      consistent with prior studies in adults with attention-deficit/hyperactivity
      disorder.

PMID- 24309907
TI  - Lethal herpesvirosis in 16 captive horned vipers (Vipera ammodytes ammodytes):
      pathological and ultrastructural findings.
AB  - Sixteen captive adult horned vipers (Vipera ammodytes ammodytes) were submitted
      for necropsy examination following a 2-week history of lethargy, anorexia and
      dyspnoea. Gross lesions included widespread haemorrhage, serosanguineous
      effusions in the body cavities and multiple pinpoint white to yellow foci in the
      liver. Microscopically, there was multifocal hepatic coagulative necrosis
      associated with intranuclear acidophilic inclusion bodies in sinusoidal
      endothelial cells. Similar endothelial lesions were observed in the myocardium,
      fat bodies, kidneys and spleen. Transmission electron microscopy revealed
      numerous virions (100-110 nm) in the nuclei of endothelial cells and
      intracytoplasmic enveloped virions (140-150 nm) were also found. The gross and
      histological findings and the ultrastructural features of the intranuclear
      inclusions and viral particles were consistent with herpesviral infection. To the
      best of our knowledge, these are the first reported cases of a lethal
      herpesvirosis in horned vipers and the second report in snakes.

PMID- 24309908
TI  - PCR as a screening test for invasive aspergillosis in haematological patients: a
      pilot study.
AB  - Invasive aspergillosis is a leading cause of morbidity and mortality in
      immunocompromised patients, particularly in individuals with haematological
      malignancy and in haematopoietic stem cell transplant recipients. Nowadays, the
      galactomannan (GM) assay has been widely used as an indication of invasive
      aspergillosis, even though the test is known to generate false-positive results.
      The aim of this study was to compare the performance of GM and real-time PCR
      (qPCR) to detected Aspergillus in blood samples obtained from high-risk
      haematological patients. Haematological patients were screened twice weekly with
      GM testing, which was performed by the Platelia ELISA kit. An additional sample
      of whole blood (4 ml) was obtained for the purpose of qPCR testing. Sixty-four
      samples from 12 patients with haematopoietic stem cell transplant or
      haematological malignancy were studied. The overall accordance between GM and
      qPCR tests was 96.9 % (62 samples). Only two samples showed contradictory
      results, with positive GM test and negative real-time PCR results. Based on the
      high concordance between GM and qPCR in terms of negative results, the main
      utility of qPCR could be in the confirmation of positive results seen with GM
      testing.

PMID- 24309909
TI  - Strong dependence of surface plasmon resonance and surface enhanced Raman
      scattering on the composition of Au-Fe nanoalloys.
AB  - Nanoalloys of noble metals with transition metals are crucial components for the
      integration of plasmonics with magnetic and catalytic properties, as well as for
      the production of low-cost photonic devices. However, due to synthetic challenges
      in the realization of nanoscale solid solutions of noble metals and transition
      metals, very little is known about the composition dependence of plasmonic
      response in nanoalloys. Here we demonstrate for the first time that the elemental
      composition of Au-Fe nanoalloys obtained by laser ablation in liquid solution can
      be tuned by varying the liquid environment. Due to surface passivation and
      reaction with thiolated ligands, the nanoalloys obtained by our synthetic
      protocol are structurally and colloidally stable. Hence, we studied the
      dependence of the surface plasmon resonance (SPR) on the iron fraction and, for
      the first time, we observed surface enhanced Raman scattering (SERS) in Au-Fe
      nanoalloys. SPR and SERS performances are strongly affected by the iron content
      and are investigated using analytical and numerical models. By demonstrating the
      strong modification of plasmonic properties on the composition, our results
      provide important insights into the exploitation of Au-Fe nanoalloys in
      photonics, nanomedicine, magneto-plasmonic and plasmon-enhanced catalysis.
      Moreover, our findings show that several other plasmonic materials exist beyond
      gold and silver nanostructures. 

PMID- 24309910
TI  - Serious violence by people with mental illness: national clinical survey.
AB  - This study aimed to estimate the prevalence of mental disorder in offenders
      convicted of serious violence, examine their social and clinical characteristics,
      and compare them with patients convicted of homicide. We examined a national
      clinical survey of all people convicted of serious violence in England and Wales
      in 2004. Mental disorder was measured by contact with mental health services
      within 12 months of the offense. Of the 5,966 serious violent offenders, 293 (5%)
      had been in recent contact with mental health services. Personality disorder (63,
      22%) and schizophrenia (55, 19%) were the most common diagnoses. Most had
      previous convictions for violence (168, 61%). Seventy-two (25%) patients were at
      high risk of violence and 34 (49%) were not subject to the Care Programme
      Approach. Compared with serious violence offenders, homicide offenders were more
      likely to have been patients (293, 5% vs. 65, 10%; p < .01). We conclude that
      patients were responsible for a small proportion of serious violent offenses;
      however, high-risk patients require closer supervision, and regular inquiry about
      changing delusional beliefs, thoughts of violence, and weapon carriage. 

PMID- 24309911
TI  - Imagination and survival.

PMID- 24309912
TI  - The minister as healer, the healer as minister.
AB  - A major task of the minister is that of healer, and with the healing task come
      some special opportunities. These relate to the therapy of the word, awakening in
      all the tragic sense of life, an identity with the wounded healer, distinguishing
      between healing and curing, and accepting the medical education enterprise as a
      patient. The healer as minister broadens the healing community into a priesthood
      of all believers. Further, our rich heritage of healing is anchored in the
      biblical tradition, and a study of this will show a similarity between ancient
      and modern healing. 

PMID- 24309913
TI  - Reconsidering three dichotomies.
AB  - Certain dichotomies that are built into modern medical and psychiatric care-mind
      versus body, the individual versus the group, and "sin" versus sickness-are
      discussed and criticized. Judeo-Christian views regarding these issues are
      presented as helpful alternatives that can help set limits on the distinctions
      made. 

PMID- 24309914
TI  - Therapeutic neutrality reconsidered.
AB  - This paper suggests that therapists' tendency to ignore the impact of their own
      religious beliefs on their patients constitutes an area of potential abuse of
      psychotherapy. The author reviews the religious stance of the founders of
      psychotherapy, as well as recent criticisms of the therapeutic process, and
      proposes steps to safeguard against the inadvertent fostering of therapists'
      religious views on the patient. 

PMID- 24309915
TI  - The Sabbath and mental health intervention: Some parallels.
AB  - This paper attempts to draw analogies between the Sabbath and certain mental
      health interventions. These interventions are derived from a family centered
      education program developed by the author for teachers and student and related to
      social group work. Five interventions characterizing this program were extracted
      and compared with Abraham Joshua Heschel's philosophy of the Sabbath: simulation,
      here-and-now emphasis, private reflection, emphasis on process, and positive
      feedback. The author concludes that both the Sabbath and family centered
      education oriented interventions should reinforce a deeper understanding and
      appreciation of one another. 

PMID- 24309916
TI  - Madness as religious experience: The case of Allen Ginsberg.
AB  - Various writers have considered madness to be a religious experience. On the
      basis of the literature in the area and conversations with psychiatric patients,
      it is argued that madness as a religious experience can be viewed as a four-stage
      developmental process. The four stages are: 1) The hurt-and-be-hurt state of
      being, 2) The self-induced psychedelic experience, 3) The confusion-and-dread
      reaction, and 4) The reconstruction-with-insight world view. To clarify how these
      four stages make up a religious experience, the poet Allen Ginsberg's so-called
      psychotic episode is organized around each of the stages. 

PMID- 24309917
TI  - Repression and sublimation in religious personalities.
AB  - Like all intense experiencing, religious life is particular: one's feelings are
      tied to specific people, through specific actions, and in specific contexts.
      Descriptive typologies, like that of Capps and Capps inThe Religious Personality,
      reflect the contours of specific selfunderstanding, but by themselves they do not
      permit one to compare hierarchically the types that sare uncovered. Abstract
      theoreies, like psychoanalysis, are not particularistic, but they do permit one
      to conceive of a hierarchy of mental functioning. Capps and Capps's typology of
      Aesthetic, Chastised, Resigned, and Dfraternal religious selves can be improved
      by placing each self along the continuum that stretches from repressed
      (maladaptive) to sublimated (adaptive) functioning. 

PMID- 24309918
TI  - Navigation, robotics, and intraoperative imaging in spinal surgery.
AB  - Spinal navigation is a technique gaining increasing popularity. Different
      approaches as CT-based or intraoperative imaging-based navigation are available,
      requiring different methods of patient registration, bearing certain advantages
      and disadvantages. So far, a large number of studies assessed the accuracy of
      pedicle screw implantation in the cervical, thoracic, and lumbar spine,
      elucidating the advantages of image guidance. However, a clear proof of patient
      benefit is missing, so far. Spinal navigation is closely related to
      intraoperative 3D imaging providing an imaging dataset for navigational use and
      the opportunity for immediate intraoperative assessment of final screw position
      giving the option of immediate screw revision if necessary. Thus, postoperative
      imaging and a potential revision surgery for screw correction become
      dispensable.Different concept of spinal robotics as the DaVinci system and
      SpineAssist are under investigation. 

PMID- 24309919
TI  - Sagittal balance, a useful tool for neurosurgeons?
AB  - New instrumentation techniques have made any correction of the spinal
      architecture possible. Sagittal balance has been described as an important
      parameter for assessing spinal deformity in the early 1970s, but over the last
      decade its importance has grown with the published results in terms of overall
      quality of life and fusion rate. Up until now, most of the studies have
      concentrated on spinal deformity surgery, but its use in the daily neurosurgery
      practice remains uncertain and may warrant further studies. 

PMID- 24309920
TI  - Novel surgical approach in the management of longitudinal pathologies within the
      spinal canal: the split laminotomy and "archbone" technique: alternative to
      multilevel laminectomy or laminotomy.
AB  - Multilevel laminectomy to open the spinal canal carries the risk of spinal
      deformities and instability. With the aim of preserving and reconstructing the
      posterior structures the authors developed a novel, minimally invasive,
      multilevel spinous process splitting and distracting laminotomy approach with or
      without complementary corticocancellous iliac crest or PEEK cage "archbone"
      grafting. The technique allows exploration of the spinal canal and the removal of
      intramedullary pathologies. Moderate enlargement of the spinal canal with
      preservation of the majority of posterior structures is also possible, so that
      muscle attachments remain intact and postoperative complications are
      substantially reduced.This surgical approach, while fulfilling the requirements
      of previous laminotomy techniques, helps to prevent damage to the crucial
      posterior stabilizers of the spine. In contrast to conventional spinal canal
      approaches, preservation of the majority of posterior structures is possible,
      leaving muscle attachments on the spinous processes and laminae completely
      intact.Furthermore, the procedure for exposure and decompression of the spinal
      canal is a suitable method for all spinal segments, the cervical, thoracic, and
      the lumbar spine in all age groups. 

PMID- 24309921
TI  - Surgery for kyphosis.
AB  - Kyphosis is a difficult topic of spinal surgery, and its management contains many
      controversies. Surgical management needs consideration of different aspects of
      the kyphotic deformity such as neurological status, the presence of spinal cord
      compression, angle of the kyphosis, the quality of bone, and accompanying
      diseases. In case of significant cord compression and neurological compromise,
      anterior surgery should have the priority. However, in smooth-angled kyphosis and
      ankylosing spondylitis patients, deformity can easily be reduced by a posterior
      only approach. Since they have no neurological deficits, and large spinal canals,
      most suitable patients for pedicle subtraction osteotomy are the patients with
      ankylosing spondylitis.In lumbar kyphosis one-level pedicle subtraction osteotomy
      (especially at L2 or L3 levels), in thoracic kyphosis multilevel osteotomies, and
      in cervicothoracic kyphosis an osteotomy at C7-T1 level should be
      preferred.Pedicle subtraction osteotomy is a technically demanding procedure that
      requires surgeons to perform meticulous technique and consider biomechanical
      issues to achieve satisfactory results and avoid complications. An attempt to
      correct the rigid fixed spinal deformity is a difficult task and requires the
      capability of a highly experienced spine surgeon. Although the physical outcome
      and patient satisfaction of surgical treatment is quite good, risks and
      complications should always be considered by both the physician and patient. 

PMID- 24309922
TI  - Cervical disc arthroplasty: a critical review and appraisal of the latest
      available evidence.
AB  - Anterior cervical discectomy and fusion (ACDF) has been a very successful
      procedure in the management of cervical radiculopathy and myelopathy. Concerns
      with adjacent segment disease and the desire to preserve physiological motion
      have led to technological and clinical efforts for cervical disc arthroplasty.
      The suggested move to cervical disc replacement has led to this latter procedure
      being one of the most scrutinised surgical treatments in the twenty-first
      century. Short- and medium-term prospective randomised clinical trials and
      systematic reviews show cervical disc replacement to be at least as good as ACDF
      as regards the clinical outcomes in the management of degenerative cervical
      spondylosis. This is logical since the neural decompression procedure is
      essentially the same. However, the rationale for arthroplasty over arthrodesis
      has been built on two main proposed roles: the preservation of segmental motion
      and the prevention of adjacent segment disease. Whilst results thus far show that
      this first role seems to be achieved, its clinical significance is as yet
      unproven; the second is so far not proven. In addition, the long-term fate of the
      implants is also unknown. Long-term safety and efficacy, therefore, still await
      further clinical studies. 

PMID- 24309923
TI  - Pedicle-Based Non-fusion Stabilization Devices: A Critical Review and Appraisal
      of Current Evidence.
AB  - Over the last decades, spinal fusion has become one of the most important
      principles in surgical treatment of spinal pathologies. Despite the undoubted
      benefits of fusion surgery, there are several drawbacks associated with this
      technique, including adjacent segment degeneration and pseudoarthrosis. Based on
      biomechanical data, dynamic stabilization of the spine is intended to ameliorate
      adjacent level degeneration by stabilizing vertebral motion in defined planes and
      mimicking natural spine movements.In this paper, we review the literature and
      discuss past and present pedicle-based non-fusion dynamic stabilization devices.
      Although there is a paucity of high-quality prospective trials, studies have
      indicated both promising and disappointing results. In comparison to 360 degrees 
      fusion surgery, the perioperative risk seems to be lower. Other complications
      like screw loosening, however, have been reported with various systems, while a
      reduction of adjacent segment disease has not yet been demonstrated. The
      necessary degree of restabilization to achieve pain-free motion seems to vary
      greatly between patients and current systems are far from perfection. If these
      problems can be solved, dynamic stabilization may nevertheless be an important
      option of spinal surgery in the future. 

PMID- 24309924
TI  - Juvenile chronic arthritis and the craniovertebral junction in the paediatric
      patient: review of the literature and management considerations.
AB  - INTRODUCTION: Juvenile chronic arthritis (JCA) is a systemic disease of childhood
      affecting particularly joints. JCA is a heterogeneous group of inflammatory joint
      disorders with onset before the age of 16 years and is comprised of 7 subtype
      groups. The pathogenesis of JCA seen in the cervical spine is synovial
      inflammation, hyperaemia, and pannus formation at the occipitoatlantoaxial joints
      resulting in characteristic craniovertebral junction findings. Treatment of
      craniovertebral junction instability as a result of JCA is a challenge. The best
      treatment strategy may be difficult because of various radiological and clinical
      severities. A review of the literature and management considerations is
      presented. REVIEW: No randomised controlled trial or systematic review on this
      subject has been published. Only experts' opinions, case reports, and case series
      have been described. Thirty-four studies have been reviewed in this study.
      Involvement of the cervical spine in patients with JCA can lead to pain and
      functional disability. The subtypes that usually affect the cervical spine are
      the polyarticular type and systemic onset type and rarely the pauciarticular
      type. The most common cervical spine changes related to JCA are as follows: (1)
      apophyseal joint ankylosis at C2-C3, (2) atlantoaxial subluxation, (3)
      atlantoaxial impaction, (4) atlantoaxial rotatory fixation, and (5) growth
      disturbances of the cervical spine. The incidence of severe subluxations has
      decreased in the last decade as result of antirheumatoid drugs and biologicals.
      However, neurological compromise still occurs in JCA patients necessitating
      surgical treatment. CONCLUSION: Whenever the cervical spine is involved in
      rheumatoid arthritis patients without neurological deficits, conservative
      treatment is legitimate. Once patients develop neurological signs and symptoms,
      surgical treatment should be considered with particular focus to age, severity of
      the disease, and general health condition. Skilled anaesthesia is crucial and the
      surgical procedure should only be carried out in centres with experience in
      craniovertebral junction abnormalities.

PMID- 24309925
TI  - Combined chelation of lead (II) by deferasirox and deferiprone in rats as
      biological model.
AB  - In order to investigate the capability of two chelators deferasirox (DFX or
      ICL670) and deferiprone (L1) in removing lead from the body, the present research
      was performed. Two does levels of 40 and 80 mg/kg body weight of lead (II)
      chloride was given to rats as biological model for 45 days. After 45 days, some
      toxicity symptoms were observed in rats such as loss of hair and weight,
      appearance of red dots around eyes, weakness and irritability. After lead
      application, chelation therapy with DFX and L1 as mono and combined (DFX, L1 and
      DFX + L1) was done for 10 days. After chelation therapy, lead level in different
      tissues reduced. The combined chelation therapy results showed that these
      chelators are able to remove lead from the body and toxicity symptoms decreased.
      The combined therapy results (DFX + L1) show higher efficacy and lower toxicity
      compared to single therapies. 

PMID- 24309926
TI  - Pilot study of individuals with diabetic macular edema undergoing cataract
      surgery.

PMID- 24309927
TI  - Caspase-2 promotes cytoskeleton protein degradation during apoptotic cell death.
AB  - The caspase family of proteases cleaves large number of proteins resulting in
      major morphological and biochemical changes during apoptosis. Yet, only a few of
      these proteins have been reported to selectively cleaved by caspase-2. Numerous
      observations link caspase-2 to the disruption of the cytoskeleton, although it
      remains elusive whether any of the cytoskeleton proteins serve as bona fide
      substrates for caspase-2. Here, we undertook an unbiased proteomic approach to
      address this question. By differential proteome analysis using two-dimensional
      gel electrophoresis, we identified four cytoskeleton proteins that were degraded
      upon treatment with active recombinant caspase-2 in vitro. These proteins were
      degraded in a caspase-2-dependent manner during apoptosis induced by DNA damage,
      cytoskeleton disruption or endoplasmic reticulum stress. Hence, degradation of
      these cytoskeleton proteins was blunted by siRNA targeting of caspase-2 and when
      caspase-2 activity was pharmacologically inhibited. However, none of these
      proteins was cleaved directly by caspase-2. Instead, we provide evidence that in
      cells exposed to apoptotic stimuli, caspase-2 probed these proteins for
      proteasomal degradation. Taken together, our results depict a new role for
      caspase-2 in the regulation of the level of cytoskeleton proteins during
      apoptosis. 

PMID- 24309928
TI  - Triptolide induces apoptosis in human leukemia cells through caspase-3-mediated
      ROCK1 activation and MLC phosphorylation.
AB  - The diterpene triepoxide triptolide is a major active component of Tripterygium
      wilfordii Hook F, a popular Chinese herbal medicine with the potential to treat
      hematologic malignancies. In this study, we investigated the roles of triptolide
      in apoptosis and cell signaling events in human leukemia cell lines and primary
      human leukemia blasts. Triptolide selectively induced caspase-dependent cell
      death that was accompanied by the loss of mitochondrial membrane potential,
      cytochrome c release, and Bax translocation from the cytosol to the mitochondria.
      Furthermore, we found that triptolide dramatically induced ROCK1
      cleavage/activation and MLC and MYPT phosphorylation. ROCK1 was cleaved and
      activated by caspase-3, rather than RhoA. Inhibiting MLC phosphorylation by ML-7
      significantly attenuated triptolide-mediated apoptosis, caspase activation, and
      cytochrome c release. In addition, ROCK1 inhibition also abrogated MLC and MYPT
      phosphorylation. Our in vivo study showed that both ROCK1 activation and MLC
      phosphorylation were associated with the tumor growth inhibition caused by
      triptolide in mouse leukemia xenograft models. Collectively, these findings
      suggest that triptolide-mediated ROCK1 activation and MLC phosphorylation may be
      a novel therapeutic strategy for treating hematological malignancies. 

PMID- 24309929
TI  - Death of p53-defective cells triggered by forced mitotic entry in the presence of
      DNA damage is not uniquely dependent on Caspase-2 or the PIDDosome.
AB  - Much effort has been put in the discovery of ways to selectively kill p53
      deficient tumor cells and targeting cell cycle checkpoint pathways has revealed
      promising candidates. Studies in zebrafish and human cell lines suggested that
      the DNA damage response kinase, checkpoint kinase 1 (Chk1), not only regulates
      onset of mitosis but also cell death in response to DNA damage in the absence of
      p53. This effect reportedly relies on ataxia telangiectasia mutated (ATM)
      dependent and PIDDosome-mediated activation of Caspase-2. However, we show that
      genetic ablation of PIDDosome components in mice does not affect cell death in
      response to gamma-irradiation. Furthermore, Chk1 inhibition largely failed to
      sensitize normal and malignant cells from p53(-/-) mice toward DNA damaging
      agents, and p53 status did not affect the death-inducing activity of DNA damage
      after Chk1 inhibition in human cancer cells. These observations argue against
      cross-species conservation of a Chk1-controlled cell survival pathway demanding
      further investigation of the molecular machinery responsible for cell death
      elicited by forced mitotic entry in the presence of DNA damage in different cell
      types and model organisms. 

PMID- 24309930
TI  - Pin1 modulates p63alpha protein stability in regulation of cell survival,
      proliferation and tumor formation.
AB  - The homolog of p53 gene, p63, encodes multiple p63 protein isoforms. TAp63
      proteins contain an N-terminal transactivation domain similar to that of p53 and
      function as tumor suppressors; whereas DeltaNp63 isoforms, which lack the intact
      N-terminal transactivation domain, are associated with human tumorigenesis.
      Accumulating evidence demonstrating the important roles of p63 in development and
      cancer development, the regulation of p63 proteins, however, is not fully
      understood. In this study, we show that peptidyl-prolyl isomerase Pin1 directly
      binds to and stabilizes TAp63alpha and DeltaNp63alpha via inhibiting the
      proteasomal degradation mediated by E3 ligase WWP1. We further show that Pin1
      specifically interacts with T538P which is adjacent to the P550PxY543 motif, and
      disrupts p63alpha-WWP1 interaction. In addition, while Pin1 enhances TAp63alpha
      mediated apoptosis, it promotes DeltaNp63alpha-induced cell proliferation.
      Furthermore, knockdown of Pin1 in FaDu cells inhibits tumor formation in nude
      mice, which is rescued by simultaneous knockdown of WWP1 or ectopic expression of
      DeltaNp63alpha. Moreover, overexpression of Pin1 correlates with increased
      expression of DeltaNp63alpha in human oral squamous cell carcinoma samples.
      Together, these results suggest that Pin1-mediated modulation of DeltaNp63alpha
      may have a causative role in tumorigenesis. 

PMID- 24309931
TI  - A candidate anti-HIV reservoir compound, auranofin, exerts a selective 'anti
      memory' effect by exploiting the baseline oxidative status of lymphocytes.
AB  - Central memory (T(CM)) and transitional memory (T(TM)) CD4(+) T cells are known
      to be the major cellular reservoirs for HIV, as these cells can harbor a
      transcriptionally silent form of viral DNA that is not targeted by either the
      immune system or current antiretroviral drug regimens. In the present study, we
      explored the molecular bases of the anti-HIV reservoir effects of auranofin (AF),
      a pro-oxidant gold-based drug and a candidate compound for a cure of AIDS. We
      here show that T(CM) and T(TM) lymphocytes have lower baseline antioxidant
      defenses as compared with their naive counterpart. These differences are mirrored
      by the effects exerted by AF on T-lymphocytes: AF was able to exert a pro
      differentiating and pro-apoptotic effect, which was more pronounced in the memory
      subsets. AF induced an early activation of the p38 mitogen-activated protein
      kinase (p38 MAPK) followed by mitochondrial depolarization and a final burst in
      intracellular peroxides. The pro-differentiating effect was characterized by a
      downregulation of the CD27 marker expression. Interestingly, AF-induced apoptosis
      was inhibited by pyruvate, a well-known peroxide scavenger, but pyruvate did not
      inhibit the pro-differentiating effect of AF, indicating that the pro-apoptotic
      and pro-differentiating effects involve different pathways. In conclusion, our
      results demonstrate that AF selectively targets the T(CM)/T(TM) lymphocyte
      subsets, which encompass the HIV reservoir, by affecting redox-sensitive cell
      death pathways.

PMID- 24309932
TI  - Cancer-derived immunoglobulin G promotes tumor cell growth and proliferation
      through inducing production of reactive oxygen species.
AB  - Cancer cells have been found to express immunoglobulin G (IgG), but the exact
      functions and underlying mechanisms of cancer-derived IgG remain elusive. In this
      study, we first confirmed that downregulation of IgG restrained the growth and
      proliferation of cancer cells in vitro and in vivo. To elucidate its mechanism,
      we carried out a co-immunoprecipitation assay in HeLa cells and identified 27
      potential IgG-interacting proteins. Among them, receptor of activated protein
      kinase C 1 (RACK1), ras-related nuclear protein (RAN) and peroxiredoxin 1 (PRDX1)
      are closely related to cell growth and oxidative stress, which prompted us to
      investigate the mechanism of action of IgG in the above phenomena. Upon
      confirmation of the interactions between IgG and the three proteins, further
      experiments revealed that downregulation of cancer-derived IgG lowered levels of
      intracellular reactive oxygen species (ROS) by enhancing cellular total
      antioxidant capacity. In addition, a few ROS scavengers, including catalase
      (CAT), dimethylsulfoxide (DMSO), n-acetylcysteine (NAC) and superoxide dismutase
      (SOD), further inhibited the growth of IgG-deficient cancer cells through
      suppressing mitogen-activated protein kinase/extracellular-regulated kinase
      (MAPK/ERK) signaling pathway induced by a low level of intracellular ROS, whereas
      exogenous hydrogen peroxide (H2O2) at low concentration promoted their survival
      via increasing intracellular ROS levels. Similar results were obtained in an
      animal model and human tissues. Taken together, our results demonstrate that
      cancer-derived IgG can enhance the growth and proliferation of cancer cells via
      inducing the production of ROS at low level. These findings provide new clues for
      understanding tumor proliferation and designing cancer therapy. 

PMID- 24309933
TI  - Keratan sulfate expression in microglia is diminished in the spinal cord in
      experimental autoimmune neuritis.
AB  - Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barre
      syndrome, an inflammatory demyelination disease of the peripheral nervous system.
      Although this disease has been extensively studied on peripheral nerves, the
      pathology of the central nervous system has not been fully understood. Previous
      studies demonstrate that expression of keratan sulfate (KS), the sugar chain of
      proteoglycan, is associated with activated microglia/macrophages accumulated
      after neuronal injuries. Unexpectedly, we found here that KS is rather diminished
      in rat EAN. KS was restrictively expressed in microglia in the spinal cord of
      normal rats. KS was positive in 50% microglia in the ventral horn and 20% in the
      dorsal horn. In EAN, microglia increased in number and expressed the activation
      marker CD68, but KS expression was abolished. Concomitantly, pro-inflammatory
      cytokines, i.e., interferon (IFN)-gamma, interleukin (IL)-1beta, and tumor
      necrosis factor (TNF)-alpha, were increased in the spinal cord of EAN rats,
      whereas anti-inflammatory cytokines, such as IL-4 and IL-10, were decreased. In
      addition, silencing of KSGal6ST attenuated KS expression on the primary cultured
      microglia and upregulated expression of some activation markers (TNF-alpha, IL
      1beta, and iNOS) under the stimulation with lipopolysaccharide and IFN-gamma.
      This study demonstrates for the first time a close association of EAN and
      disappearance of KS on microglia. KS expression could be a useful marker to
      evaluate the status of polyneuropathy. 

PMID- 24309934
TI  - Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells.
AB  - In recent years, studies of cancer development and recurrence have been
      influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs)
      hypothesis. According to this, cancer is sustained by highly positioned,
      chemoresistant cells with extensive capacity of self renewal, which are
      responsible for disease relapse after chemotherapy. Growth of cancer cells as
      three-dimensional non-adherent spheroids is regarded as a useful methodology to
      enrich for cells endowed with CSC-like features. We have recently reported that
      cell cultures derived from malignant pleural effusions (MPEs) of patients
      affected by adenocarcinoma of the lung are able to efficiently form spheroids in
      non-adherent conditions supplemented with growth factors. By expression
      profiling, we were able to identify a set of genes whose expression is
      significantly upregulated in lung tumor spheroids versus adherent cultures. One
      of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the
      main enzyme responsible for the conversion of saturated into monounsaturated
      fatty acids. In the present study, we show both by RNA interference and through
      the use of a small molecule inhibitor that SCD1 is required for lung cancer
      spheroids propagation both in stable cell lines and in MPE-derived primary tumor
      cultures. Morphological examination and image analysis of the tumor spheroids
      formed in the presence of SCD1 inhibitors showed a different pattern of growth
      characterized by irregular cell aggregates. Electron microscopy revealed that the
      treated spheroids displayed several features of cellular damage and
      immunofluorescence analysis on optical serial sections showed apoptotic cells
      positive for the M30 marker, most of them positive also for the stemness marker
      ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells
      with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were
      strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These
      results suggest that SCD1 is a critical target in lung cancer tumor-initiating
      cells. 

PMID- 24309935
TI  - Low-dose triptolide in combination with idarubicin induces apoptosis in AML
      leukemic stem-like KG1a cell line by modulation of the intrinsic and extrinsic
      factors.
AB  - Leukemia stem cells (LSCs) are considered to be the main reason for relapse and
      are also regarded as a major hurdle for the success of acute myeloid leukemia
      chemotherapy. Thus, new drugs targeting LSCs are urgently needed. Triptolide
      (TPL) is cytotoxic to LSCs. Low dose of TPL enhances the cytotoxicity of
      idarubicin (IDA) in LSCs. In this study, the ability of TPL to induce apoptosis
      in leukemic stem cell (LSC)-like cells derived from acute myeloid leukemia cell
      line KG1a was investigated. LSC-like cells sorted from KG1a were subjected to
      cell cycle analysis and different treatments, and then followed by in vitro
      methyl thiazole tetrazolium bromide cytotoxicity assay. The effects of different
      drug combinations on cell viability, intracellular reactive-oxygen species (ROS)
      activity, colony-forming ability and apoptotic status were also examined.
      Combination index-isobologram analysis indicates a synergistic effect between TPL
      and IDA, which inhibits the colony-forming ability of LSC-like cells and induces
      their apoptosis. We further investigated the expression of Nrf2, HIF-1alpha and
      their downstream target genes. LSC-like cells treated with both TPL and IDA have
      increased levels of ROS, decreased expression of Nrf2 and HIF-1alpha pathways.
      Our findings indicate that the synergistic cytotoxicity of TPL and IDA in LSCs
      like cells may attribute to both induction of ROS and inhibition of the Nrf2 and
      HIF-1alpha pathways. 

PMID- 24309936
TI  - Direct modulation of the outer mitochondrial membrane channel, voltage-dependent
      anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced
      cell death.
AB  - Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell
      proliferation and induces cell death of cancer cells and activated immune cells.
      It is not an agonist of the classical CB1/CB2 cannabinoid receptors and the
      mechanism by which it functions is unknown. Here, we studied the effects of CBD
      on various mitochondrial functions in BV-2 microglial cells. Our findings
      indicate that CBD treatment leads to a biphasic increase in intracellular calcium
      levels and to changes in mitochondrial function and morphology leading to cell
      death. Density gradient fractionation analysis by mass spectrometry and western
      blotting showed colocalization of CBD with protein markers of mitochondria.
      Single-channel recordings of the outer-mitochondrial membrane protein, the
      voltage-dependent anion channel 1 (VDAC1) functioning in cell energy, metabolic
      homeostasis and apoptosis revealed that CBD markedly decreases channel
      conductance. Finally, using microscale thermophoresis, we showed a direct
      interaction between purified fluorescently labeled VDAC1 and CBD. Thus, VDAC1
      seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1
      by CBD may be responsible for the immunosuppressive and anticancer effects of
      CBD. 

PMID- 24309937
TI  - Long-term cultured mesenchymal stem cells frequently develop genomic mutations
      but do not undergo malignant transformation.
AB  - Cultured human umbilical cord mesenchymal stem cells (hUC-MSCs) are being tested
      in several clinical trials and encouraging outcomes have been observed. To
      determine whether in vitro expansion influences the genomic stability of hUC
      MSCs, we maintained nine hUC-MSC clones in long-term culture and comparatively
      analyzed them at early and late passages. All of the clones senesced in culture,
      exhibiting decreased telomerase activity and shortened telomeres. Two clones
      showed no DNA copy number variations (CNVs) at passage 30 (P30). Seven clones had
      >=1 CNVs at P30 compared with P3, and one of these clones appeared trisomic
      chromosome 10 at the late passage. No tumor developed in immunodeficient mice
      injected with hUC-MSCs, regardless of whether the cells had CNVs at the late
      passage. mRNA-Seq analysis indicated that pathways of cell cycle control and DNA
      damage response were downregulated during in vitro culture in hUC-MSC clones that
      showed genomic instability, but the same pathways were upregulated in the clones
      with good genomic stability. These results demonstrated that hUC-MSCs can be
      cultured for many passages and attain a large number of cells, but most of the
      cultured hUC-MSCs develop genomic alterations. Although hUC-MSCs with genomic
      alterations do not undergo malignant transformation, periodic genomic monitoring
      and donor management focusing on genomic stability are recommended before these
      cells are used for clinical applications. 

PMID- 24309938
TI  - Prognostic and therapeutic relevance of FLIP and procaspase-8 overexpression in
      non-small cell lung cancer.
AB  - Non-small cell lung carcinoma remains by far the leading cause of cancer-related
      deaths worldwide. Overexpression of FLIP, which blocks the extrinsic apoptotic
      pathway by inhibiting caspase-8 activation, has been identified in various
      cancers. We investigated FLIP and procaspase-8 expression in NSCLC and the effect
      of HDAC inhibitors on FLIP expression, activation of caspase-8 and drug
      resistance in NSCLC and normal lung cell line models. Immunohistochemical
      analysis of cytoplasmic and nuclear FLIP and procaspase-8 protein expression was
      carried out using a novel digital pathology approach. Both FLIP and procaspase-8
      were found to be significantly overexpressed in tumours, and importantly, high
      cytoplasmic expression of FLIP significantly correlated with shorter overall
      survival. Treatment with HDAC inhibitors targeting HDAC1-3 downregulated FLIP
      expression predominantly via post-transcriptional mechanisms, and this resulted
      in death receptor- and caspase-8-dependent apoptosis in NSCLC cells, but not
      normal lung cells. In addition, HDAC inhibitors synergized with TRAIL and
      cisplatin in NSCLC cells in a FLIP- and caspase-8-dependent manner. Thus, FLIP
      and procaspase-8 are overexpressed in NSCLC, and high cytoplasmic FLIP expression
      is indicative of poor prognosis. Targeting high FLIP expression using HDAC1-3
      selective inhibitors such as entinostat to exploit high procaspase-8 expression
      in NSCLC has promising therapeutic potential, particularly when used in
      combination with TRAIL receptor-targeted agents. 

PMID- 24309940
TI  - Sixty years in algal physiology and photosynthesis.
AB  - This personal perspective records research experiences in chemistry and biology
      at four German universities, two before and two after World War II. The research
      themes came from cytophysiology of green unicellular algae, in particular their
      photosynthesis. The function of inorganic ions in photosynthesis and dark
      respiration was investigated at different degrees of specific mineral stress
      (deficiencies), and the kinetics of recovery followed after the addition of the
      missing element. Two types of recovery of photosynthesis were observed: indirect
      restitution via growth processes and immediate normalisation. From the latter
      case (K(+), phosphate, Mn(++)) the effect of manganese was emphasized as its role
      in photosynthetic O2 evolution became established during our research. Other
      themes of our group, with some bearing on photosynthesis were: synchronization of
      cell growth by light-dark change and effects of blue (vs. red) light on the
      composition of green cells. Some experiences in connection with algal mass
      cultures are included. Discussion of several editorial projects shows how
      photosynthesis, as an orginally separated field of plant biochemistry and
      biophysics, became included into general cell physiology and even ecophysiology
      of green plants. The paper contains an appreciation of the authors' main mentor
      Kurt Noack (1888-1963) and of Ernst Georg Pringsheim (1881-1970), founder of
      experimental phycology. 

PMID- 24309939
TI  - Wentilactone A as a novel potential antitumor agent induces apoptosis and G2/M
      arrest of human lung carcinoma cells, and is mediated by HRas-GTP accumulation to
      excessively activate the Ras/Raf/ERK/p53-p21 pathway.
AB  - Chemotherapy remains the common therapeutic for patients with lung cancer. Novel,
      selective antitumor agents are pressingly needed. This study is the first to
      investigate a different, however, effective antitumor drug candidate Wentilactone
      A (WA) for its development as a novel agent. In NCI-H460 and NCI-H446 cell lines,
      WA triggered G2/M phase arrest and mitochondrial-related apoptosis, accompanying
      the accumulation of reactive oxygen species (ROS). It also induced activation of
      mitogen-activated protein kinase and p53 and increased expression of p21. When we
      pre-treated cells with ERK, JNK, p38, p53 inhibitor or NAC followed by WA
      treatment, only ERK and p53 inhibitors blocked WA-induced apoptosis and G2/M
      arrest. We further observed Ras (HRas, KRas and NRas) and Raf activation, and
      found that WA treatment increased HRas-Raf activation. Knockdown of HRas by using
      small interfering RNA (siRNA) abolished WA-induced apoptosis and G2/M arrest.
      HRas siRNA also halted Raf, ERK, p53 activation and p21 accumulation. Molecular
      docking analysis suggested that WA could bind to HRas-GTP, causing accumulation
      of Ras-GTP and excessive activation of Raf/ERK/p53-p21. The direct binding
      affinity was confirmed by surface plasmon resonance (SPR). In vivo, WA suppressed
      tumor growth without adverse toxicity and presented the same mechanism as that in
      vitro. Taken together, these findings suggest WA as a promising novel, potent and
      selective antitumor drug candidate for lung cancer. 

PMID- 24309941
TI  - Activities of carboxylating enzymes in the CAM species Opuntia ficus-indica grown
      under current and elevated CO2 concentrations.
AB  - Responses of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and
      phosphoenolpyruvate carboxylase (PEPCase) to an elevated atmospheric CO2
      concentration were determined along with net CO2 uptake rates for the
      Crassulacean acid metabolism species Opuntia ficus-indica growing in open-top
      chambers. During the spring 13 months after planting, total daily net CO2 uptake
      of basal and first-order daughter cladodes was 28% higher at 720 than at 360 MUl
      CO2 l(-1). The enhancement, caused mainly by higher CO2 assimilation during the
      early part of the night, was also observed during late summer (5 months after
      planting) and the following winter. The activities of Rubisco and PEPCase
      measured in vitro were both lower at the elevated CO2 concentration, particularly
      under the more favorable growth conditions in the spring and late summer. Enzyme
      activity in second-order daughter cladodes increased with cladode age, becoming
      maximal at 6 to 10 days. The effect ofelevated CO2 on Rubisco and PEPCase
      activity declined with decreasing irradiance, especially for Rubisco. Throughout
      the 13-month observation period, O. ficus-indica thus showed increased CO2 uptake
      when the atmospheric CO2 concentration was doubled despite lower activities of
      both carboxylating enzymes. 

PMID- 24309942
TI  - Probing protein structural requirements for formation of the core light
      harvesting complex of photosynthetic bacteria using hybrid reconstitution
      methodology.
AB  - The alpha- and beta-polypeptides of LH1 isolated from four different
      photosynthetic bacteria (Rhodospirillum rubrum, Rhodobacter sphaeroides,
      Rhodobacter capsulatus and Rhodopseudomonas viridis) were used for homologous and
      hybrid reconstitution experiments with bacteriochlorophyll a. Formation of B820
      type subunit complexes and LH1-type complexes were evaluated. The beta
      polypeptides of R. rubrum, Rb. sphaeroides and Rb. capsulatus behaved similarly
      and formed B820-type subunit complexes in the absence of an alpha-polypeptide.
      The alpha- and beta-polypeptides were both required to form a LH1-type complex
      with each of these three homologous systems. In hybrid experiments where the beta
      polypeptides were tested for reconstitution with alpha-polypeptides other than
      their homologous partners, half of the twelve possible combinations resulted in
      formation of both B820- and LH1-type complexes. Three of the combinations that
      did not result in formation of a LH1-type complex involved the beta-polypeptide
      of R. rubrum. It is suggested that these latter results can be explained by
      charge repulsion between the Lys at position-17 (assigning the conserved His
      located nearest to the C-terminus as position 0) in the beta-polypeptide of R.
      rubrum and each of the heterologous alpha-polypeptides tested, all of which have
      an Arg at this location. Conclusions that can be derived from these experimental
      results include: (1) the experimental data support the idea that a central core
      region of approximately 40 amino acids exists in each of the polypeptides, which
      contains sufficient information to allow formation of both the B820- and LH1-type
      complexes and (2) a specific portion of the N-terminal hydrophilic region of each
      polypeptide was found in which ion pairs between oppositely charged groups on the
      alpha- and beta-polypeptides seem to stabilize complex formation. 

PMID- 24309943
TI  - Probing the structure of the core light-harvesting complex (LH1) of
      Rhodopseudomonas viridis by dissociation and reconstitution methodology.
AB  - A subunit complex was formed from the core light-harvesting complex (LH1) of
      bacteriochlorophyll(BChl)-b-containing Rhodopseudomonas viridis. The addition of
      octyl glucoside to a carotenoid-depleted Rps. viridis membrane preparation
      resulted in a subunit complex absorbing at 895 nm, which could be quantitatively
      dissociated to free BChl b and then reassociated to the subunit. When carotenoid
      was added back, the subunit could be reassociated to LH1 with a 25% yield.
      Additionally, the Rps. viridis alpha- and beta-polypeptides were isolated,
      purified, and then reconstituted with BChl b. They formed a subunit absorbing
      near 895 nm, similar to the subunit formed by titration of the carotenoid
      depleted membrane, but did not form an LH1-type complex at 1015 nm. The same
      results were obtained with the beta-polypeptide alone and BChl b. Isolated
      polypeptides were also tested for their interaction with BChl a. They formed
      subunit and LH1-type complexes similar to those formed using polypeptides
      isolated from BChl-a-containing bacteria but displayed 6-10 nm smaller red shifts
      in their long-wavelength absorption maxima. Thus, the larger red shift of BChl-b
      containing Rps. viridis is not attributable solely to the protein structure. The
      beta-polypeptide of Rps. viridis differed from the other beta-polypeptides tested
      in that it could form an LH1-type complex with BChl a in the absence of the alpha
      and gamma-polypeptides. It apparently contains the necessary information
      required to assemble into an LH1-type complex. When the gamma-polypeptide was
      tested in reconstitution with BChl a and BChl b with the alpha- and beta
      polypeptides, it had no effect; its role remains undetermined. 

PMID- 24309944
TI  - Variable thermal dissipation in a Photosystem I submembrane fraction.
AB  - Photoacoustic spectroscopy was used to study the thermal deactivation processes
      in a Photosystem I submembrane fraction isolated from spinach. A large part of
      the thermal dissipation was variable. The yield of this variable thermal emission
      depended on the redox state of the Photosystem. It increased with the measuring
      modulated light intensity coinciding with the gradual closure of the reaction
      centers. Thermal deactivation was maximal when the reaction centers were closed
      by a saturating illumination. Extrapolation of the data at zero light intensity
      indicated that the yield of non-variable thermal emission represented about 37%
      of the maximal emission. The presence of methylviologen as artificial electron
      acceptor decreased the yield of variable thermal emission whereas inhibition
      following heat stress treatments increased it. The significance of the variable
      and non-variable components of thermal dissipation is discussed and the measured
      energy storage is suggested to originate from the reduction of the plastoquinone
      pool during cyclic electron transport around Photosystem I. 

PMID- 24309945
TI  - Polypeptide sequence of the chlorophyll a/b/c-binding protein of the
      prasinophycean alga Mantoniella squamata.
AB  - The primary structure of the Chla/b/c-binding protein from Mantoniella squamata
      is determined. This is the first report that protein sequencing reveals one
      modified amino acid resulting in a LHCP-specific TFA-cleavage site. The
      comparison of the sequence of Mantoniella with other Chla/b-and Chla/c-binding
      proteins shows that the modified amino acid is located in a region which is
      highly conserved in all these proteins. The alignment also reveals that the LHCP
      of Mantoniella is related to the Chla/b-binding proteins. Finally, possible Chl
      binding regions are discussed. 

PMID- 24309946
TI  - Evidence for the existence of trimeric and monomeric Photosystem I complexes in
      thylakoid membranes from cyanobacteria.
AB  - In cyanobacteria, solubilization of thylakoid membranes by detergents yields both
      monomeric and trimeric Photosystem I (PS I) complexes in variable amounts. We
      present evidence for the existence of both monomeric and trimeric PS I in
      cyanobacterial thylakoid membranes with the oligomeric state depending 'in vitro'
      on the ion concentration. At low salt concentrations (i.e.<=10 mM MgSO4) PS I is
      mainly extracted as a trimer from these membranes and at high salt concentrations
      (i.e.>=150 mM MgSO4) nearly exclusively as a monomer, irrespective of the type of
      salt used (i.e. mono- or bivalent ions) and the temperature (i.e. 4 degrees C or
      20 degrees C). Once solubilized, the PS I trimer is stable over a wide range of
      ion concentrations (i.e. beyond 0.5 M). A model is presented which suggests a
      monomer-oligomer equilibrium of PS I, but also of PS II and the cyt. b6/f-complex
      in the cyanobacterial thylakoid membrane. The possible physiological role of this
      equilibrium in the regulation of state transitions is discussed. 

PMID- 24309947
TI  - Light-harvesting chlorophyll a-b complex requirement for regulation of
      Photosystem II photochemistry by non-photochemical quenching.
AB  - Recently, it has been suggested (Horton et al. 1992) that aggregation of the
      light-harvesting a-b complex (LHC II) in vitro reflects the processes which occur
      in vivo during fluorescence induction and related to the major non-photochemical
      quenching (qE). Therefore the requirement of this chlorophyll a-b containing
      protein complex to produce qN was investigated by comparison of two barley
      mutants either lacking (chlorina f2) or depressed (chlorina(104)) in LHC II to
      the wild-type and pea leaves submitted to intermittent light (IL) and during
      their greening in continuous light.It was observed that qN was photoinduced in
      the absence of LHC II, i.e. in IL grown pea leaves and the barley mutants.
      Nevertheless, in these leaves qN had no (IL, peas) or little (barley mutants)
      inhibitory effect on the photochemical efficiency of QA reduction measured by
      flash dosage response curves of the chlorophyll fluorescence yield increase
      induced by a single turn-over flashDuring greening in continuous light of IL pea
      leaves, an inhibitory effect on QA photoreduction associated to qN developed as
      Photosystem II antenna size increased with LHC II synthesis. Utilizing data from
      the literature on connectivity between PS II units versus antenna size, the
      following hypothesis is put forward to explain the results summarized above. qN
      can occur in the core antenna or Reaction Center of a fraction of PS II units and
      these units will not exhibit variable fluorescence. Other PS II units are
      quenched indirectly through PS II-PS II exciton transfer which develops as the
      proportion of connected PS II units increases through LHC II synthesis. 

PMID- 24309948
TI  - A simple, single-tube radioisotopic assay for the phosphorylation/inactivation
      activity of the pyruvate,orthophosphate dikinase regulatory protein.
AB  - A simple, single-tube radiolsotopic method has been developed to assay the
      relative phosphorylation (inaetivation) activity of the bifunctional regulatory
      protein (RP) of C4-leaf pyruvate,orthophosphate dikinase (PPDK) in desalted leaf
      homogenates and partially purified preparations. RP catalyzes the inactivation of
      maize PPDK by phosphorylation of Thr-456, utilizing [beta-P]ADP as the specific
      phosphoryl donor. Existing spectrophotometric and radioisotopic assays for the
      detection of RP activity are either relatively insensitive or labor-intensive and
      timeconsuming. We describe a modified radioisotopic assay that couples the
      synthesis of [beta-(32)P]ADP by exogenous adenylate kinase with the subsequent RP
      catalyzed [beta-(32)P]ADP-dependent phosphorylation of exogenous maize PPDK. The
      incorporation of [beta-(32)P] is dependent on the initial concentrations of ATP
      and PPDK, as well as the presence of active RP. Desalted leaf homogenates of C3
      species fail to catalyze (32)P incorporation into exogenous maize PPDK.
      Conversely, heterologous systems containing the maize target enzyme and leaf
      homogenats of other C4 species result in PPDK-specific (32)P-incorporation. This
      simple radioisotopic assay is at least 40-times more sensitive than the routine
      spectrophotometric assay, and qualitatively exhibits comparable sensitivity and
      requires significantly less time than the currently available radioisotopic RP
      assay. The present assay reliably generates [beta-(32)P]ADP and as such may be
      useful for studies of other systems requiring beta-labeled ADP, which is not
      commercially available. 

PMID- 24309949
TI  - The 1932 experiments.
AB  - The 1932 papers of Emerson and Arnold were great ones, both conceptually and
      experimentally. The results were so far out of synch with the thinking of the
      times that it took many years for them to become a cozy part of the dogma of
      photosynthesis. I reflect on this twenty-four year segment of history. 

PMID- 24309951
TI  - The innovator's DNA and health care improvement.

PMID- 24309950
TI  - Exercise as a vital sign: a quasi-experimental analysis of a health system
      intervention to collect patient-reported exercise levels.
AB  - BACKGROUND: Lack of regular physical activity is highly prevalent in U.S. adults
      and significantly increases mortality risk. OBJECTIVE: To examine the clinical
      impact of a newly implemented program ("Exercise as a Vital Sign" [EVS]) designed
      to systematically ascertain patient-reported exercise levels at the beginning of
      each outpatient visit. DESIGN AND PARTICIPANTS: The EVS program was implemented
      in four of 11 medical centers between April 2010 and October 2011 within a single
      health delivery system (Kaiser Permanente Northern California). We used a quasi
      experimental analysis approach to compare visit-level and patient-level outcomes
      among practices with and without the EVS program. Our longitudinal observational
      cohort included over 1.5 million visits by 696,267 adults to 1,196 primary care
      providers. MAIN MEASURES: Exercise documentation in physician progress notes;
      lifestyle-related referrals (e.g. exercise programs, nutrition and weight loss
      consultation); patient report of physician exercise counseling; weight change
      among overweight/obese patients; and HbA1c changes among patients with diabetes.
      KEY RESULTS: EVS implementation was associated with greater exercise-related
      progress note documentation (26.2 % vs 23.7 % of visits, aOR 1.12 [95 % CI: 1.11
      1.13], p < 0.001) and referrals (2.1 % vs 1.7 %; aOR 1.14 [1.11-1.18], p < 0.001)
      compared to visits without EVS. Surveyed patients (n = 6,880) were more likely to
      report physician exercise counseling (88 % vs. 76 %, p < 0.001). Overweight
      patients (BMI 25-29 kg/m(2), n = 230,326) had greater relative weight loss (0.20
      [0.12 - 0.28] lbs, p < 0.001) and patients with diabetes and baseline HbA1c > 7.0
      % (n = 30,487) had greater relative HbA1c decline (0.1 % [0.07 %-0.13 %], p <
      0.001) in EVS practices compared to non-EVS practices. CONCLUSIONS:
      Systematically collecting exercise information during outpatient visits is
      associated with small but significant changes in exercise-related clinical
      processes and outcomes, and represents a valuable first step towards addressing
      the problem of inadequate physical activity.

PMID- 24309952
TI  - Capsule commentary on Fontil, et al. physician underutilization of effective
      medications for resistant hypertension at office visits in the United States:
      NAMCS 2006-2010.

PMID- 24309953
TI  - Synthesis, structure, and catalytic activity of novel trinuclear rare-earth metal
      amido complexes incorporating MU-eta5:eta1 bonding indolyl and MU3-oxo groups.
AB  - The reactions of different pyrrolyl-functionalized indoles with rare-earth
      metal(III) amides [(Me3Si)2N]3RE(III)(MU-Cl)Li(THF)3 (RE = Yb, Er, Dy, Eu, Y)
      produced different kinds of rare-earth metal amido complexes. Reactions of N-((1H
      pyrrol-2-yl)methylene)-2-(1H-indol-3-yl)ethanamine with rare-earth metal amides
      [(Me3Si)2N]3RE(III)(MU-Cl)Li(THF)3 (RE = Yb, Er, Dy, Eu, Y) in toluene or THF at
      temperatures of 75-80  degrees C afforded the novel trinuclear rare-earth metal
      amido complexes incorporating the indolyl ligand in MU-eta(5):eta(1) bonding
      modes and a MU3-O group, which is believed to originate from cleavage of the THF
      ring based on experimental results. Reactions of 2-(1H-indol-3-yl)-N-((1-methyl
      1H-pyrrol-2-yl)methylene)ethanamine with rare-earth metal(III) amides
      [(Me3Si)2N]3RE(III)(MU-Cl)Li(THF)3 (RE = Yb, Dy) produced mononuclear ytterbium
      and dysprosium amides having the indolyl ligand in an eta(1) bonding fashion. The
      results indicate that substituents not only have an influence on reactivity, but
      also have an influence on the bonding of the indolyl ligands with metals. The
      catalytic activities of the novel lanthanide amido complexes for the
      hydrophosphonylation of both aromatic and aliphatic aldehydes and ketones were
      explored. The results indicate that these complexes display a high catalytic
      activity for the C-P bond formation under mild conditions when using low catalyst
      loadings (0.1 mol% for aldehydes and ketones). Thus, it provides a potential way
      to prepare alpha-hydroxy phosphonates.

PMID- 24309954
TI  - The acute respiratory distress syndrome: incidence and mortality, has it changed?
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine and discuss the
      incidence and outcome of patients with the acute respiratory distress syndrome
      (ARDS). This is a challenging task, as there is no specific clinical sign or
      diagnostic test that accurately identifies and adequately defines this syndrome.
      RECENT FINDINGS: This review will focus on published epidemiological studies
      reporting population-based incidence of ARDS, as defined by the American-European
      Consensus Conference criteria. In addition, the current outcome figures for ARDS
      patients reported in observational and randomized controlled trials will be
      reviewed. The focus will be on studies published since 2000, when the ARDSnet
      study on protective mechanical ventilation was published, although particular
      emphasis will be on those articles published in the last 24 months. SUMMARY: On
      the basis of current evidence, and despite the order of magnitude of reported
      European and USA incidence figures, it seems that the incidence and overall
      mortality of ARDS has not changed substantially since the original ARDSnet study.
      The current mortality of adult ARDS is still greater than 40%.

PMID- 24309955
TI  - Monocyte-platelets aggregates as cellular biomarker of endothelium-dependent
      coronary vasomotor dysfunction in patients with coronary artery disease.
AB  - Monocyte-platelet aggregates (MPA) are increased in patients with acute coronary
      syndrome. We investigated whether MPA are associated with the presence of
      functionally significant coronary stenoses or with coronary arterial endothelial
      dysfunction. One hundred forty five patients undergoing elective coronary
      angiography were prospectively enrolled. Functional significance of coronary
      stenosis was assessed by fractional flow reserve (FFR). Thirty randomly selected
      patients underwent pacing protocol to evaluate Coronary endothelium-dependent
      vasomotor function (CVF). Whole blood was drawn to evaluate MPA. In patients with
      FFR <= 0.8 (FFRpos, n = 75), MPA did not significantly differ from FFR >0.8
      patients (FFRneg, n = 70) (38.1% [25.7-56.6] vs. 34.0% [20.5-49.9], p = 0.08).
      CVF was similar in FFRpos and FFRneg patients (percent vessel diameter change,
      %VDC = 7.19 % [6.01-10.9] vs. 8.0 % [0.81-9.80], p = 0.78). Yet, patients with
      abnormal CVF showed higher MPA as compared to patients with preserved CVF (28.3%
      [28.8-53.4] vs. 20.5 % [17.0-32.9], p = 0.01). Moreover, MPA was inversely
      correlated with %VDC (R2 = 0.26, p < 0.01). MPA levels are significantly higher
      in patients with abnormal coronary vasomotor function regardless of the presence
      of functionally significant coronary stenosis.

PMID- 24309956
TI  - Measurement of novel biomarkers to predict chronic heart failure outcomes and
      left ventricular remodeling.
AB  - Myocardial remodeling is pivotal in the progression and complication of chronic
      heart failure (HF). We assessed serial measurement of five biomarkers with
      biologic links to remodeling (biglycan, secreted frizzled-related protein 3,
      endostatin, insulin-like growth factor binding protein 7 [IGFBP7], mimecan) in
      142 patients with HF followed through 882 office visits. IGFBP7 and mimecan were
      most associated with events; in fully adjusted models, lower IGFBP7
      concentrations across visits independently predicted fewer events (odds ratio
      [OR] = 0.83; 95 % confidence interval [CI] = 0.73-0.95, p = 0.01). Subjects with
      rising mimecan had greater decrease in left ventricular end diastolic (p = 0.07)
      and systolic (p = 0.01) volumes, greater increase in ejection fraction (p =
      0.02), and had lowest event rates. Statistical models suggested several HF
      medications might lead to changes in both IGFBP7 and mimecan values. The results
      suggest serial measurement of IGFBP7 provides prognostic information, while
      changes in mimecan provide unique information regarding myocardial remodeling.

PMID- 24309958
TI  - Topological morphology conversion towards SnO2/SiC hollow sphere nanochains with
      efficient photocatalytic hydrogen evolution.
AB  - Novel SnO2/SiC hollow sphere nanochains were synthesized by topological
      morphology conversion of SnO2@C core-shell nanochains through a vapour-solid
      reaction. Evaluation of the SnO2/SiC HSNCs for the generation of hydrogen
      revealed that they exhibit excellent catalytic activity and durability. 

PMID- 24309957
TI  - Impact of aspirin dosing on the effects of P2Y12 inhibition in patients with
      acute coronary syndromes.
AB  - The discovery of the antiplatelet effect of low-dose aspirin led to the hugely
      successful strategy of dual antiplatelet therapy in patients with acute coronary
      syndromes (ACS). Increasing the dose of aspirin beyond 75-100 mg has never been
      shown to offer additional efficacy in ACS patients but could possibly increase
      the risk of bleeding. In the Platelet Inhibition and Patients Outcome (PLATO)
      study, higher doses of aspirin appeared to neutralise the additional benefit of
      the potent P2Y12 inhibitor ticagrelor compared to clopidogrel (Circulation 124:
      544-554, 2011). However, higher doses of aspirin have not been shown to have an
      adverse interaction with the potent P2Y12 inhibition provided by prasugrel and
      double-dose clopidogrel (Journal of the American College of Cardiology, 2013, in
      press; N Engl J Med 363: 930-942, 2010). This potentially suggests that the
      mechanism for this interaction is not related to the inhibition of platelet P2Y12
      receptors or could simply be a chance finding. 

PMID- 24309959
TI  - Double-bond location in monounsaturated fatty acids by dimethyl disulfide
      derivatization and mass spectrometry: Application to analysis of fatty acids in
      pheromone glands of four lepidoptera.
AB  - A rapid analytical procedure for the determination of the position of double
      bonds in mixtures of monounsaturated fatty acid methyl esters has been developed.
      The method is based on direct capillary GC-MS-EI analysis of dimethyl disulfide
      adducts. The procedure was applied to mixtures of monounsaturated fatty esters
      from pheromone gland extracts of three tortricids from theChoristoneura genus,C.
      fumiferana, C. occidentalis, andC. pinus pinus, and one noctuid from the
      Plusiinae subfamily,Plusia chalcites. A correlation was found between the known
      major pheromone components in the four species with the corresponding fatty
      acids. Some of the additional fatty acids may be precursors to as yet
      unidentified minor pheromone components, present in extremely small quantities,
      in these species. 

PMID- 24309960
TI  - Effects of ferulic acid, an allelopathic compound, on leaf expansion of cucumber
      seedlings grown in nutrient culture.
AB  - Cucumber seeds and seedlings at various ages (7-19 days old) were treated with a
      single treatment or multiple treatments (at 2-day intervals) of ferulic acid in
      nutrient culture. Ferulic acid treatments of cucumber seeds during stages of
      germination and radicle growth did not significantly reduce subsequent seedling
      growth. Ferulic acid treatments to seedlings reduced leaf area, leaf expansion,
      and dry weight of cucumber seedlings. Pretreatment of seeds and seedlings with
      0.1 or 0.2 mM ferulic acid did not modify the effects of a single 1 mM ferulic
      acid treatment on leaf expansion when a single treatment was given at various
      times to seedlings ranging from 7 to 19 days of age. Treatments of 1mM or greater
      induced rapid wilting of leaves, but visible recovery occurred within 24-48 hr
      and subsequent treatments did not cause wilting. Once seedlings were removed from
      ferulic acid treatments, leaf expansion resumed. The magnitude of recovery
      depended on the concentration of ferulic acid, frequency of ferulic acid
      application and age of the seedling. Mean relative rates of leaf expansion
      recovered rapidly even in the presence of ferulic acid. Recovery of leaf
      expansion after ferulic acid treatments was faster for seedlings grown in an
      adequate nutrient environment than for seedlings grown in a limited nutrient
      environment. Ferulic acid disappeared from nutrient solutions with time, and two
      microbial metabolic products of ferulic acid (i.e., vanillic and protocatechuic
      acid) were identified in nutrient solutions. 

PMID- 24309961
TI  - Mass spectral determination of aldehydes, ketones, and carboxylic acids using 1,1
      dimethylhydrazine.
AB  - Analyses of nanogram to milligram quantities of aliphatic aldehydes, fatty acids,
      and unhindered aliphatic ketones such as those typically found in pheromonal
      blends have been effected by treating these mixtures with 1,1-dimethylhydrazine.
      The aldehydes and ketones formN,N-dimethylhydrazones, while the fatty acids form
      methyl esters. Structural elucidation of the reaction products was achieved using
      EI and CI gas chromatography-mass spectrometry. 

PMID- 24309962
TI  - Cucurbitacins : Plant-derived defense compounds for diabroticites (Coleoptera:
      Chrysomelidae).
AB  - Four species of diabroticites with different host specificities are shown for the
      first time to sequester cucurbitacins. While all beetles fed on an artificial
      diet (no cucurbitacins) were readily consumed by Chinese praying mantids, a
      significant proportion of adultDiabrotica balteata (72%),D. undecimpunctata
      howardi (46%), andD. virgifera virgifera (24%) fed on squash fruit containing
      cucurbitacins B and D were rejected. Moreover, even when adults did not feed on
      cucurbitacins, 21-24% ofAcalymma vittatum were rejected by the mantids which is
      consistent with larval sequestration of cucurbitacins. The mantids failed to
      learn to avoid any of the beetle species despite adverse effects associated with
      ingestion, i.e., uncoordination, regurgitation, etc. A cucurbitacin D metabolite
      accumulated and was sequestered for extended periods of time in the hemolymph of
      all four species. In addition, female beetles that had ingested cucurbitacins
      laid eggs containing substantial amounts of cucurbitacins. 

PMID- 24309963
TI  - Chemical regulation of polyethism during foraging in the neotropical
      termiteNasutitermes costalis.
AB  - The soldiers ofNasutitermes costalis communicate information about the presence
      and location of food by laying chemical trails of sternal gland secretion. These
      trails first recruit additional soldiers, and as the number of soldiers
      contacting food and returning to the nest increases, trail pheromone
      concentration increases, and workers are recruited. This polyethic pattern of
      recruitment does not appear to depend on qualitative (caste-specific) properties
      of soldier and worker sternal gland secretions, but rather on quantitative
      differences in pheromone production between castes. Large third-instar workers
      have significantly greater sternal gland volumes than soldiers, and glands of
      approximately equivalent size have approximately equivalent recruitment effects.
      The recruitment and orientation effects of artificial trails prepared from worker
      sternal glands can be mimicked by increasing the concentration of soldier sternal
      gland pheromone. 

PMID- 24309964
TI  - Effect of empty comb on defensive behavior of honeybees.
AB  - Honeybees in colonies with 6.36-m(2) surface area of empty comb responded faster
      to moving targets and stung the targets more often than bees from colonies with
      3.18-m(2) surface area of empty honeycomb. The two groups did not differ
      significantly in speed of response to alarm pheromone or in number of bees
      defending the colony. Volatiles from the comb are suggested as primer pheromones
      for defensive behavior. 

PMID- 24309965
TI  - Oxidation of oleanolic acid ofAvicennia officinalis leaves to oleanonic acid in
      the natural environment of Sunderban mangrove ecosystem.
AB  - Oleanolic acid, a major component pentacyclic triterpene in the leaves
      ofAvicennia officinalis was found to be oxidized to oleanonic acid in the natural
      environment of Sunderban mangrove forest. 

PMID- 24309966
TI  - Multichemical defense of plant bugHotea gambiae (westwood) (Heteroptera:
      Scutelleridae) : Sesquiterpenoids from abdominal gland in larvae.
AB  - Chemical defense in larvae of the plant bugHotea gambiae has been investigated.
      Results of analyses (GC, GC-MS) on the secretions from the three dorsally
      situated larval abdominal defense (scent) glands are reported. The secretion from
      the first abdominal gland consists of a mixture of C10 and C15 isoprenoids: (C10)
      alpha-pinene, beta-pinene, limonene, beta-phellandrene; (C15) beta-caryophyllene,
      caryophyllene oxide, alpha-humulene, and (the major component) humulene epoxide
      II. The secretions from the second and third abdominal glands are similar
      mixtures consisting of (E)-2-decenal, (E)-4-oxohex-2-enal, andn-tridecane
      together with lesser amounts of (E)-2-hexenal,n-dodecane, and other materials.
      Isoprenoid defense is now known from four species of plant bugs (Heteroptera)
      associated with Malvaceae. 

PMID- 24309967
TI  - Exocrine secretions of bees : VI. Unsaturated ketones and aliphatic esters in the
      Dufour's gland secretion ofDufourea novaeangliae (Hymenoptera: Halictidae).
AB  - The volatile components of the Dufour's gland extracts ofDufourea novaeangliae
      were analyzed by gas chromatography-mass spectroscopy. The following were
      identified: a series of five bis-homologous unsaturated ketones ranging from C10
      to C18, a series of nine bis-homologous hexanoates ranging from C8 to C24, a
      series of three bis-homologous octanoates ranging from C8 to C12, and hexanoic,
      hexadecanoic, and octadecanoic acids. The ketones are all new natural products
      reported for bees. Several of these unsaturated ketones were also identified in
      extracts of the provision masses from their nest cells. Male mandibular gland
      extracts contained citral. 

PMID- 24309968
TI  - Studies on possible role of catecholamines in regulation of sex pheromone gland
      activity in American dog tick,Dermacentor veriabilis (Say).
AB  - Administered monoamines affected sex pheromone activity in the foveal glands of
      the tick,Dermacentor variabilis (Say). Flooding the tissues of the female tick
      with reserpine, alpha-methyl-m-tyrosine methyl ester hydrochloride, and
      pilocarpine prior to feeding led to reductions in female sex attractant activity
      during engorgement. Similar treatments with cyclic AMP, dopamine, serotonin, 6
      hydroxydopamine, and acetylcholine had no apparent effects on the attractiveness
      of feeding females. Assays (by gas chromatography) demonstrated substantial
      reductions in 2,6-dichlorophenol content following treatment with alpha-methyl-m
      tyrosine methyl ester, pilocarpine, and, in most cases, with reserpine. Reserpine
      was effective only when administered in near-lethal concentrations to unfed
      females. In contrast, treatment with dopamine led to elevated 2,6-dichlorophenol
      content in most trials. X-ray microanalysis corroborated the evidence with
      reserpine and dopamine. These and other findings reported elsewhere implicate
      monoamines, presumably catecholamines, in the regulation of sex pheromone
      secretion in this species. The significance of these findings for understanding
      the physiological mechanisms involved in the regulation of sex pheromone
      secretion and biosynthesis is discussed. 

PMID- 24309969
TI  - HPLC separation and wavelength area ratios of more than 50 phenolic acids and
      flavonoids.
AB  - Relative retention times and wavelength area ratios for over 50 standard
      compounds were calculated using reverse-phase HPLC. The standard compounds
      analyzed included benzoic acids, cinnamic acids, benzene carboxylic acids, acetic
      acids, coumarins, benzaldehydes and a variety of flavonoid compounds including
      flavanones, flavones, isoflavones, and their glycosides. Each standard compound
      was chromatographed by three different gradient elutions. Compounds were detected
      by UV absorption at 254 nm and 280 nm. Relative retention times with respect to
      two different internal references and the 254nm: 280nm wavelength area ratio was
      determined for each standard. Soybean root and seed extracts were analyzed for
      the presence of the standard compounds using the chromatographic conditions
      described. 

PMID- 24309970
TI  - Male olive fruit fly attraction to synthetic sex pheromone components in
      laboratory and field tests.
AB  - Male olive fruit fly attraction to the four synthetic components of the female
      sex attractant pheromone was studied under laboratory and field conditions. In
      laboratory tests males responded to all four components tested separately.
      Component I, (1,7-dioxaspiro[5.5]undecane) was more attractive than any of the
      remaining three components alone, but a combination of all four was more
      attractive than component I alone. In field tests with polyethylene vials as
      pheromone dispensers, the complete mixture, although not statistically
      significant, was constantly more attractive to males than component I alone. A
      tendency of enhancement of attraction of component I by combining it with
      component II (alpha-pinene) or III (n-nonanal) was also observed. In field tests
      with rubber septa as pheromone dispensers only component I was attractive.
      Mixtures containing component I were also attractive but not more attractive than
      component I alone. Evaporation rate and ratio of components as they come out of
      the dispenser appear to be critical for male response. 

PMID- 24309971
TI  - Attraction of bark beetles (Coleoptera: Scolytidae) to a pheromone trap
      Experiment and mathematical models.

PMID- 24309972
TI  - Structural and functional analysis of single neurons to correlate synaptic
      connectivity with grooming behavior.
AB  - We describe a protocol to image the complex axonal branching structure of
      identified mechanosensory neurons in Drosophila, combined with a behavioral assay
      to evaluate the functional output of the neuron. The stimulation of identified
      mechanosensory neurons in live animals produces a stereotyped grooming reflex.
      The mechanosensory axonal arbor within the CNS is subsequently labeled with a
      lipophilic fluorescent dye and imaged by fluorescence microscopy. The behavioral
      output can therefore be correlated to the axonal morphology of the stimulated
      neuron in the same animal. Combining this protocol with genetic analysis provides
      a powerful tool for identifying the roles of molecules involved in different
      aspects of hard-wired neural circuit formation underlying an innate behavior.
      From behavioral analysis to axonal imaging, the protocol takes 4 d. 

PMID- 24309973
TI  - The synthesis of tetra-modified RNA for the multidimensional control of gene
      expression via light-activated RNA interference.
AB  - Light-activated RNA interference (LARI) is an effective way to control gene
      expression with light. This, in turn, allows for the spacing, timing and degree
      of gene expression to be controlled by the spacing, timing and amount of light
      irradiation. The key mediators of this process are siRNA or dsRNA that have been
      modified with four photocleavable groups of dimethoxy nitro phenyl ethyl (DMNPE),
      located on the four terminal phosphate groups of the duplex RNA. These mediators
      can be easily synthesized and purified using two readily available products:
      synthetic RNA oligonucleotides and DMNPE-hydrazone. The synthesis of the tetra
      DMNPE-modified duplex RNA is made possible by a remarkable regiospecificity of
      DMNPE for terminal phosphates (over internal phosphates or nucleobases) that we
      have previously identified. The four installed DMNPE groups effectively limit
      RNAi until irradiation cleaves them, releasing native, active siRNA. By using the
      described protocol, any process that is mediated by RNAi can be controlled with
      light. Although other methods exist to control gene expression with light by
      using specialized reagents, this method requires only two commercially available
      products. The protocol takes ~3 d in total for the preparation of modified RNA. 

PMID- 24309974
TI  - Preparation of carboxylate derivatives of terpyridine via the furan pathway.
AB  - This protocol describes a practical procedure for the preparation of terpyridine
      carboxy derivatives, which have numerous applications, including being
      photoactive components of functional materials, and which can be used in
      medicinal chemistry or in catalysis. This protocol relies on the permanganate
      mediated oxidation of a furan ring on the polypyridine system. The procedure
      involves three stages. First, a furan-functionalized terpyridine is synthesized
      from furfuraldehyde and a 2-acetylpyridine derivative. Second, the furan ring is
      oxidized thus providing a carboxylic acid. Finally, esters are prepared by
      reaction of the acids in refluxing alcohols. The procedure is simple, uses a
      reagent available from renewable resources (furfural) and avoids the use of
      noxious reagents or solvents, thus making it more environmentally friendly when
      compared with previously described methods. The whole protocol can be conducted
      in ~10 d, including isolation and drying of intermediates and products. 

PMID- 24309975
TI  - Synthesis and use of QCy7-derived modular probes for the detection and imaging of
      biologically relevant analytes.
AB  - This protocol describes the synthesis of modular turn-ON QCy7-based probes for
      the detection of biologically relevant analytes, such as hydrogen peroxide,
      ubiquitous sulfhydryl and beta-galactosidase. The probes presented herein are
      prepared through a simple procedure that involves the preliminary alkylation of 4
      hydroxy-isophthalaldehyde with a relevant analyte-responsive protecting group,
      followed by condensation of the resulting product with 2 equivalents of sulfo
      indolium moieties. Evaluation of the turn-ON near-IR fluorescence response to
      their relevant analytes for the three different QCy7 probes is also reported. The
      preparation of a QCy7 diagnostic probe requires 1-2 d. Probes for other analytes
      can be prepared according to this modular procedure by incorporating a specific
      analyte-responsive group as a triggering substrate. 

PMID- 24309976
TI  - Proteome-wide enrichment of proteins modified by lysine methylation.
AB  - We present a protocol for using the triple malignant brain tumor domains of
      L3MBTL1 (3xMBT), which bind to mono- and di-methylated lysine with minimal
      sequence specificity, in order to enrich for such methylated lysine from cell
      lysates. Cells in culture are grown with amino acids containing light or heavy
      stable isotopic labels. Methylated proteins are enriched by incubating cell
      lysates with 3xMBT, or with the binding-null D355N mutant as a negative control.
      Quantitative liquid chromatography and tandem mass spectrometry (LC-MS/MS) are
      then used to identify proteins that are specifically enriched by 3xMBT pull-down.
      The addition of a third isotopic label allows the comparison of protein lysine
      methylation between different biological conditions. Unlike most approaches, our
      strategy does not require a prior hypothesis of candidate methylated proteins,
      and it recognizes a wider range of methylated proteins than any available method
      using antibodies. Cells are prepared by growing in isotopic labeling medium for
      about 7 d; the process of enriching methylated proteins takes 3 d and analysis by
      LC-MS/MS takes another 1-2 d. 

PMID- 24309977
TI  - An investigation into the dental health of children with obesity: an analysis of
      dental erosion and caries status.
AB  - AIM: To investigate whether children with obesity experienced more erosion and
      caries than children with normal weight. METHODS: This study involved children
      aged 7-15 years. The study and control group comprised 32 children with BMI >
      98th centile and 32 healthy children with normal BMI-for-age, respectively.
      O'Sullivan Erosion Index and WHO Caries Index were used in the examination of
      erosion and caries, respectively. Stimulated salivary flow rate, buffering
      capacity, Streptococcus mutans and lactobacilli counts (CFU/ml) were evaluated. A
      cross-sectional questionnaire survey was employed to collect information on
      participant's demographic background, oral health history and habits, and
      utilisation of dental care services. RESULTS: Children with obesity were more
      likely to have erosion than healthy children (p < 0.001), and had more erosion in
      terms of severity (p < 0.0001) and area affected (p < 0.0001), but not in the
      number of surfaces affected (p = 0.167). Posterior teeth were less likely than
      anterior teeth to be affected by erosion (OR 0.32, 95 % CI 0.012-0.082). Gender
      had no effect on erosion. There were no statistically significant differences in
      the DMFT, saliva profiles or questionnaire responses between the groups.
      CONCLUSIONS: Children with obesity may have high risk of dental erosion, but do
      not necessarily have higher risk of dental caries than children with normal
      weight.

PMID- 24309978
TI  - A virtual outpatient department provides a satisfactory patient experience
      following endoscopy.
AB  - PURPOSE: The purpose of this study was to investigate telephone follow-up of post
      endoscopy patients as an alternative to attendance at the outpatient department.
      METHODS: Access to outpatient appointments is often a target for improvement in
      healthcare systems. Increased outpatient clinic capacity is not feasible without
      investment and extra manpower in an already constrained service. Outpatient
      attendance was audited at a busy colorectal surgical service. A subset of
      patients appropriate for follow-up in a "virtual outpatient department" (VOPD)
      were identified. A pilot study was designed and involved telephone follow-up of
      low-risk endoscopic procedures. Patient satisfaction was assessed using the
      Medical Interview Satisfaction Scale (MISS), which is a standardised survey of
      patient satisfaction with healthcare experiences. This was conducted via
      anonymous questionnaire at the end of the study. RESULTS: Of a total of 166
      patients undergoing endoscopy in the time period, 79 were prospectively recruited
      to VOPD follow-up based on eligibility criteria. Overall, 67 (84.8 %) were
      successfully followed up by telephone consultation; nine patients (11.4 %) were
      contacted by mail. The remaining three patients (3.8 %) were brought back to the
      OPD. Patients recruited were more likely to be younger (55.82 +/- 14.96 versus
      60.78 +/- 13.97 years, P = 0.029) and to have had normal examinations (49.4
      versus 31.0 %, chi (2) = 5.070, P = 0.025). Nearly three quarters of patients
      responded to the questionnaire. The mean scores for all four aspects of the MISS
      were satisfactory, and overall patients were satisfied with the VOPD experience.
      CONCLUSION: VOPD is a target for improved healthcare provision, with improved
      efficiency and a high patient satisfaction rate.

PMID- 24309979
TI  - Active smoking may negatively affect response rate, progression-free survival,
      and overall survival of patients with metastatic renal cell carcinoma treated
      with sunitinib.
AB  - BACKGROUND: Obesity, smoking, hypertension, and diabetes are risk factors for
      renal cell carcinoma development. Their presence has been associated with a worse
      outcome in various cancers. We sought to determine their association with outcome
      of sunitinib treatment in metastatic renal cell carcinoma (mRCC). METHODS: An
      international multicenter retrospective study of sunitinib-treated mRCC patients
      was performed. Multivariate analyses were performed to determine the association
      between outcome and the pretreatment status of smoking, body mass index,
      hypertension, diabetes, and other known prognostic factors. RESULTS: Between 2004
      and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers,
      67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median
      progression-free survival (PFS) was 9 months, and overall survival (OS) was 22
      months. Factors associated with PFS were smoking status (past and active smokers:
      hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p < .0001), non-clear
      cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio
      >3 (HR: 3.51, p < .0001), use of angiotensin system inhibitors (HR: 0.63, p =
      .01), sunitinib dose reduction or treatment interruption (HR: 0.72, p = .045),
      and Heng risk (good and intermediate risk: HR: 1.07, p = .77; poor risk: HR:
      1.87, p = .046). Factors associated with OS were smoking status (past and active
      smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p < .0001), pretreatment
      neutrophil-to-lymphocyte ratio >3 (HR: 2.95, p < .0001), and sunitinib-induced
      hypertension (HR: 0.57, p = .002). CONCLUSION: Active smoking may negatively
      affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider
      advising patients to quit smoking at initiation of sunitinib treatment for mRCC.

PMID- 24309980
TI  - U.S. Food and Drug Administration approval summary: omacetaxine mepesuccinate as
      treatment for chronic myeloid leukemia.
AB  - On October 26, 2012, the U.S. Food and Drug Administration (FDA) granted
      accelerated approval to omacetaxine mepesuccinate (Synribo; Teva Pharmaceuticals
      USA, Inc., North Wales, PA, http://www.tevausa.com) for the treatment of adult
      patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid
      leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase
      inhibitors (TKIs). The approval was based on the FDA review of data from 111
      patients with CML in CP or in AP who had received two or more prior TKIs,
      including imatinib. Major cytogenetic response was achieved in 18% of patients
      with CP, with a median response duration of 12.5 months. Major hematologic
      response was achieved in 14% of patients with AP, with a median response duration
      of 4.7 months. The FDA safety evaluation was based on submitted data from 163
      patients with CP or AP CML who had received at least one dose of omacetaxine
      mepesuccinate. The safety evaluation was limited by the single-arm design of the
      clinical trials as conducted in a small number of previously treated patients.
      The most common (>=20%) adverse reactions of any grade in enrolled patients
      included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue,
      asthenia, injection site reaction, pyrexia, and infection. The FDA concluded that
      omacetaxine mepesuccinate has shown activity and a favorable benefit-to-risk
      profile for the studied population of adult patients with CML (CP or AP) with
      resistance and/or intolerance to two or more TKIs. Further evidence of response
      durability to verify clinical benefit is pending. 

PMID- 24309981
TI  - Low incidence of pseudoprogression by imaging in newly diagnosed glioblastoma
      patients treated with cediranib in combination with chemoradiation.
AB  - BACKGROUND: Chemoradiation (CRT) can significantly modify the radiographic
      appearance of malignant gliomas, especially within the immediate post-CRT period.
      Pseudoprogression (PsP) is an increasingly recognized phenomenon in this setting,
      and is thought to be secondary to increased permeability as a byproduct of the
      complex process of radiation-induced tissue injury, possibly enhanced by
      temozolomide. We sought to determine whether the addition of a vascular
      endothelial growth factor (VEGF) signaling inhibitor (cediranib) to conventional
      CRT had an impact on the frequency of PsP, by comparing two groups of patients
      with newly diagnosed glioblastoma before, during, and after CRT. METHODS: All
      patients underwent serial magnetic resonance imaging as part of institutional
      review board-approved clinical studies. Eleven patients in the control group
      received only chemoradiation, whereas 29 patients in the study group received
      chemoradiation and cediranib until disease progression or toxicity. Response
      assessment was defined according to Response Assessment in Neuro-Oncology
      criteria, and patients with enlarging lesions were classified into true tumor
      progressions (TTP) or PsP, based on serial radiographic follow-up. RESULTS: Two
      patients in the study group (7%) showed signs of apparent early tumor
      progression, and both were subsequently classified as TTP. Six patients in the
      control group (54%) showed signs of apparent early tumor progression, and three
      were subsequently classified as TTP and three as PsP. The frequency of PsP was
      significantly higher in the control group. CONCLUSION: Administration of a VEGF
      inhibitor during and after CRT modifies the expression of PsP by imaging.

PMID- 24309983
TI  - Local and regional staging of invasive breast cancer with sonography: 25 years of
      practice at MD Anderson Cancer Center.
AB  - At The University of Texas MD Anderson Cancer Center, we have used sonography
      (US) extensively for more than 2 decades to refine the local and regional staging
      of invasive breast cancer. Although magnetic resonance imaging is superior to all
      other imaging modalities in the measurement of the primary tumor and detection of
      additional foci of malignancy, in our experience US has shown sufficient accuracy
      in clinical practice to stage most invasive breast cancers. The exceptions are
      ill-defined tumors such as invasive lobular cancers and tumors in breasts
      containing extensive diffuse benign disease. An advantage of US is that
      multifocality or multicentricity can be confirmed via US-guided fine-needle
      aspiration within 15 minutes and the information shared immediately with the
      patient and the breast surgeon or medical oncologist. US has also proved
      indispensable in the evaluation of lymphatic spread because it can evaluate more
      nodal basins (e.g., the supraclavicular fossa and low neck) than magnetic
      resonance imaging can and because it can guide needle biopsy to confirm the
      status of any indeterminate node (including internal mammary nodes) within
      minutes. 

PMID- 24309982
TI  - Hypothyroidism after a cancer diagnosis: etiology, diagnosis, complications, and
      management.
AB  - Hypothyroidism is a common disease that is easily treated in the majority of
      cases, when readily diagnosed; however, presentation of an aggregate of its
      symptoms is often clinically overlooked or attributed to another disease and can
      potentially be lethal. Already prevalent in older women, its occurrence in
      younger patients is rising as a result of radiation therapy, radioactive iodine
      therapy, and newer antineoplastic agents used to manage various malignancies. The
      presence of nonspecific constitutional symptoms and neuropsychiatric complaints
      in cancer patients can be attributed to a myriad of other diagnoses and
      therapies. Thyroid dysfunction can be easily overlooked in cancer patients
      because of the complexity of cancer's clinical picture, particularly in the
      pediatric population. Underdiagnosis can have important consequences for the
      management of both hypothyroidism and the malignancy. At minimum, quality of life
      is adversely affected. Untreated hypothyroidism can lead to heart failure,
      psychosis, and coma and can reduce the effectiveness of potentially life-saving
      cancer therapies, whereas iatrogenic causes can provoke atrial fibrillation and
      osteoporosis. Consequently, the diagnosis and treatment of hypothyroidism in
      cancer patients are pertinent. We summarize the history, epidemiology,
      pathophysiology, clinical diagnosis, and management of hypothyroidism in cancer
      patients. 

PMID- 24309985
TI  - Nobody here but us humanists.

PMID- 24309984
TI  - A new model for reimbursing genome-based cancer care.

PMID- 24309986
TI  - Psychoanalysis and theology: Jacques Lacan and Paul.
AB  - The nature of humanity-or the human situation-has been an area of thought
      intensely studied by theologians and philosophers for centuries. In more recent
      times, however, psychology has made serious advances into this field of inquiry.
      It has been able to provide insights applicable to previous theological ideas.
      The author brings to the reader's attention his twofold purpose: to present an
      interpretation of the human situation as understood by Jacques Lacan-as informed
      by such forerunners as Sigmund Freud and Martin Heidegger- and expressed by
      psychoanalytic method. These same ideas are then examined in light of the
      writings of St. Paul. From a sensitive study of these two thinkers the author has
      been able to draw numerous correlations pertinent to contemporary studies within
      religion and psychology. 

PMID- 24309987
TI  - Chaplain and psychiatrist as ally-rivals.
AB  - Chaplain and psychiatrist share professional concern for the improved
      psychological health of the distressed general hospital patient. Commonality of
      concern suggests regular consultative co-presence and associated
      interprofessional collaboration. This study of consultation within one teaching
      hospital finds that co-presence occurs in less than five percent of potential
      cases and that collaborative exchange in connection with those cases is rare, a
      condition supported by psychiatric staff and found regrettable by chaplains.
      "Case-typing," guided by outlooks of secularization (chaplain), scientism
      (psychiatrist), and traditionalism (ward internist), provides an accounting of
      collaborative underutilization, supplemented by considerations of organizational
      structure and positional power. 

PMID- 24309988
TI  - The terminology of the soul (atta): A psychiatric recasting.
AB  - Among all the beliefs of the Theravada Buddhist tradition, none has stirred more
      controversy than theanatta doctrine. This teaching suggests that nowhere can a
      substantial self be apprehended. On the contrary, belief in a fixed, unitive self
      is to be regarded as an ineluctable condition for the emergence of suffering
      (dukkha). Only when such a truth is grasped by means of wisdom (panna) can the
      perennial peace of Nibbana be found. By providing a model of understanding drawn
      mainly from psychoanalytic and clinical practice, this essay purports to illumine
      the pathology of exaggerated self-entitlement (narcissism) rampant during the age
      of the historical Buddha, and the latter's reaction against it by means of
      theanatta doctrine. 

PMID- 24309989
TI  - On the search for meaning.
AB  - The author demonstrates heuristic ways to differentiate healthy from pathological
      meanings in life. He argues that no one can tackle such a task without first
      detecting the purpose of life. To find it, one must recognize that, ultimately,
      life does not belong to anyone, and this on two accounts: First, it is received
      through parental union, and second, it is only temporal and must thus be "given
      back." Life is a loan that must be returned through death. These two polar
      realities, it is here believed, inform the whole of existence and guide us toward
      healthy growth (positive existential mental health). 

PMID- 24309990
TI  - A leaderless approach to a minister's peer-support group.
AB  - This article describes a support group for ministers that uses a leaderless
      approach. The group has met for over ten years and as a result of that experience
      has developed in ways that make it unique. These group characteristics are
      described and are offered as a general guide for ministers as well as members of
      other helping professions who are interested in peer support. 

PMID- 24309991
TI  - The death crisis and pastoral counseling.
AB  - Death is an event that presents a crisis to the family system. Conceptualizing
      death as a stressor event and recognizing the variety of coping resources present
      in and available to bereaved families and individuals, along with the meaning
      attached to death, can help interventionists to perceive stategies for providing
      assistance in time of grief. Pastoral counselors are often needed to interpret
      death from a faith perspective, yet they may need to interpret the family's
      reaction to the death crisis in order to facilitate their readjustment. Analysis
      of the death event using Reuben Hill's crisis equation provides a workable
      conceptual framework. 

PMID- 24309992
TI  - Religious institutions and the prevention of mental illness.
AB  - It is estimated that fifteen percent of the population is in need of some kind of
      mental health service at any given time, thus constituting a primary health
      problem. The President's Commission on Mental Health (PCMH) recognized that
      religious institutions can help to prevent mental illness by providing support in
      the community. This paper presents types of programs the PCMH found that were
      supportive and describes the program of one church to illustrate additional ways
      that clergy and their congregants, working collaboratively with professionals and
      agencies, can contribute significantly to the prevention of mental illness. 

PMID- 24309993
TI  - The religious physician.
AB  - In order to understand what it means to be a physician, we must, according to Dr.
      Edmund Pellegrino, analyze four words that capture the essence of the medical
      enterprise: profession, patient, compassion, and consent. The resultant model
      provides a rational and secular basis upon which the Jewish or Christian
      physician can then build an understanding of medicine in its peculiarly religious
      form. This religious form is likewise characterized by four words: vocation,
      neighbor, love, and covenant. An analysis of these words provides a model of and
      for the religious physician. 

PMID- 24309994
TI  - The effects of stabilizing and directional selection on phenotypic and genotypic
      variation in a population of RNA enzymes.
AB  - The distribution of variation in a quantitative trait and its underlying
      distribution of genotypic diversity can both be shaped by stabilizing and
      directional selection. Understanding either distribution is important, because it
      determines a population's response to natural selection. Unfortunately, existing
      theory makes conflicting predictions about how selection shapes these
      distributions, and very little pertinent experimental evidence exists. Here we
      study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a
      combination of high throughput genotyping and measurement of a biochemical
      phenotype allow us to address this question. We show that directional selection,
      compared to stabilizing selection, increases the genotypic diversity of an
      evolving ribozyme population. In contrast, it leaves the variance in the
      phenotypic trait unchanged. 

PMID- 24309996
TI  - In situ synthesis of large-area single sub-10 nm nanoparticle arrays by polymer
      pen lithography.
AB  - In order to take advantage of the unique properties of nanoparticles in
      integrated devices, it is desirable to position monodispersed nanoparticles on
      substrates with controlled placement. Herein, we utilize small molecules such as
      ethylene glycol (EG) or glycerol to facilitate the delivery of nanoparticle
      precursors to the substrates in the polymer pen lithography (PPL) process.
      Subsequently, large-area ordered single nanoparticle arrays, including sub-10 nm
      Ag nanoparticle, 30 nm Au nanoparticle and 80 nm Fe2O3 nanoparticle arrays have
      been synthesized in situ with controllable sizes and pitches. 

PMID- 24309995
TI  - The relationship between serum mannose-binding lectin levels and acute ischemic
      stroke risk.
AB  - Complement activation and inflammation have been suggested in the pathogenesis of
      stroke, mannose-binding lectin (MBL) were found to have roles during the process.
      The aim of this study was to investigate the relationship between acute ischemic
      stroke (AIS) and serum MBL levels in Chinese population. From January 1 to June
      30 2013, all patients with first-ever AIS were recruited to participate in the
      study. Serum MBL levels and routine test were examined. The National Institutes
      of Health Stroke Scale (NIHSS) score was assessed on admission blinded to MBL
      levels. During the inclusion period, 148 patients with AIS were registered and
      completed study. The results indicated that the serum MBL levels were
      significantly (p < 0.0001) higher in acutely ischemic stroke patients as compared
      to normal controls [1,332; interquartile range (IQR) 996-2,134 MUg/L and 897; IQR
      678-1,100 MUg/L, respectively]. There was a correlation between serum levels of
      MBL and NIHSS score [r (spearman) = 0.608, p < 0.0001). In multivariate analysis,
      serum MBL as a continuous variable was associated with an increased risk of AIS,
      after adjustment for above possible confounders (OR 1.002, 95 % CI 1.001-1.008; p
      < 0.0001). These results indicated that elevated MBL levels could be considered
      as an independent stroke risk factor in Chinese population, suggesting a role of
      MBL and the lectin pathway of complement activation in the pathogenesis of
      stroke. 

PMID- 24309998
TI  - Central rupture and bulging of low-weight polypropylene mesh following recurrent
      incisional sublay hernioplasty.
AB  - A recurrent incisional hernia resulting from the rupture of low-weight
      polypropylene mesh is rarely reported in the literature. Three patients with
      recurrent incisional hernia due to low-weight polypropylene mesh central rupture
      were operated 5, 7 and 13 months after initial sublay hernioplasty. The posterior
      myofascial layer was fully reconstructed in all patients during the hernioplasty,
      whereas the anterior myofascial layer was only partially reconstructed. The
      recurrent hernia was managed using heavy-weight polypropylene mesh; in two
      patients, a new sublay hernioplasty was performed and in one patient an "open
      preperitoneal flat mesh technique" was performed under local anaesthesia as a day
      case procedure. If closing of the anterior myofascial layer cannot be ensured
      during the incisional hernioplasty, the use of low-weight polypropylene meshes
      should be avoided; preference should be given to the heavy-weight polypropylene
      meshes.

PMID- 24309997
TI  - Cyclin dependent kinase-9 mediated transcriptional de-regulation of cMYC as a
      critical determinant of endocrine-therapy resistance in breast cancers.
AB  - Endocrine therapy resistance in estrogen receptor alpha positive (ERalpha+)
      breast cancers remains a major obstacle for maintaining efficacy of targeted
      therapies. We investigated the significance and the mechanisms involved in cMYC
      over-expression in a MCF7 derived panel of ERalpha+ breast cancer cells which can
      proliferate in the absence of estrogen with different sensitivities to anti
      hormone therapies. We show that all the resistant cell lines tested over-express
      cMYC as compared to parental MCF7 cells and its inhibition lead to the
      differential blocking of estrogen-independent proliferation in resistant cells.
      Further investigation of the resistant cell line, MCF7:5C, suggested
      transcriptional de-regulation of cMYC gene was responsible for its over
      expression. Chromatin immuno-precipitation assay revealed markedly higher
      recruitment of phosphorylated serine-2 carboxy-terminal domain (CTD) of RNA
      polymerase-II at the proximal promoter of cMYC gene, which is responsible for
      transcriptional elongation of the cMYC RNA. The level of CDK9, a factor
      responsible for the phosphorylation of serine-2 of RNA polymerase II CTD, was
      found to be elevated in all the resistant cell lines. Pharmacological inhibition
      of CDK9 not only reduced the transcripts and the protein levels of cMYC in
      MCF7:5C cells but also selectively inhibited the estrogen-independent growth of
      all the resistant cell lines. This study describes the up-stream molecular events
      involved in the transcriptional over-expression of cMYC gene in breast cancer
      cells proliferating estrogen-independently and identifies CDK9 as a potential
      novel drug target for therapeutic intervention in endocrine-resistant breast
      cancers. 

PMID- 24309999
TI  - Genetic analysis of the TBX2 gene promoter in indirect inguinal hernia.
AB  - PURPOSE: Inguinal hernia is a common disease, majority of which are indirect
      inguinal hernia (IIH). A positive family history indicates that genetic factors
      play important roles in the IIH development. To date, genetic causes for IIH
      remain unknown. T-box transcription factor 2 (TBX2) is a major regulator in the
      morphogenesis and organogenesis. The human TBX2 gene is widely expressed in fetal
      and adult tissues, including muscle and connective tissues. Therefore, we
      speculated that altered TBX2 gene expression may be involved in the IIH
      formation. METHODS: IIH patients (n = 129) and ethnic-matched healthy subjects (n
      = 198) were recruited for this study. The human TBX2 gene promoters were
      generated with PCR and directly sequenced to identify DNA sequence variants
      (DSVs). Furthermore, biological functions of the DSVs were examined with reporter
      gene constructs in cultured cells. RESULTS: Total six DSVs within the TBX2 gene
      promoter were identified. A heterozygous DSV (g.59476307G>C) was identified in an
      IIH patient, but in none of controls, which significantly decreased the TBX2 gene
      promoter activities. Another heterozygous DSV (g.59476704G>C) was only found in
      one control, which did not affect TBX2 gene promoter activities. Four DSVs,
      g.59476316C>A (rs73991913), g.59476415T>C (rs1476781), g.59476510G>C (rs4455026)
      and g.59476892C>T (rs2286524), all of which were single nucleotide polymorphisms,
      were found in both IIH patients and controls with similar frequencies.
      CONCLUSIONS: Our data suggested that the DSV within the TBX2 gene promoter was
      implicated in the IIH development as a rare cause.

PMID- 24310000
TI  - Most parsimonious reconciliation in the presence of gene duplication, loss, and
      deep coalescence using labeled coalescent trees.
AB  - Accurate gene tree-species tree reconciliation is fundamental to inferring the
      evolutionary history of a gene family. However, although it has long been
      appreciated that population-related effects such as incomplete lineage sorting
      (ILS) can dramatically affect the gene tree, many of the most popular
      reconciliation methods consider discordance only due to gene duplication and loss
      (and sometimes horizontal gene transfer). Methods that do model ILS are either
      highly parameterized or consider a restricted set of histories, thus limiting
      their applicability and accuracy. To address these challenges, we present a novel
      algorithm DLCpar for inferring a most parsimonious (MP) history of a gene family
      in the presence of duplications, losses, and ILS. Our algorithm relies on a new
      reconciliation structure, the labeled coalescent tree (LCT), that simultaneously
      describes coalescent and duplication-loss history. We show that the LCT
      representation enables an exhaustive and efficient search over the space of
      reconciliations, and, for most gene families, the least common ancestor (LCA)
      mapping is an optimal solution for the species mapping between the gene tree and
      species tree in an MP LCT. Applying our algorithm to a variety of clades,
      including flies, fungi, and primates, as well as to simulated phylogenies, we
      achieve high accuracy, comparable to sophisticated probabilistic reconciliation
      methods, at reduced run time and with far fewer parameters. These properties
      enable inferences of the complex evolution of gene families across a broad range
      of species and large data sets. 

PMID- 24310001
TI  - The spring-loaded genome: nucleosome redistributions are widespread, transient,
      and DNA-directed.
AB  - Nucleosome occupancy plays a key role in regulating access to eukaryotic genomes.
      Although various chromatin regulatory complexes are known to regulate nucleosome
      occupancy, the role of DNA sequence in this regulation remains unclear,
      particularly in mammals. To address this problem, we measured nucleosome
      distribution at high temporal resolution in human cells at hundreds of genes
      during the reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV). We
      show that nucleosome redistribution peaks at 24 h post-KSHV reactivation and that
      the nucleosomal redistributions are widespread and transient. To clarify the role
      of DNA sequence in these nucleosomal redistributions, we compared the genes with
      altered nucleosome distribution to a sequence-based computer model and in vitro
      assembled nucleosomes. We demonstrate that both the predicted model and the
      assembled nucleosome distributions are concordant with the majority of nucleosome
      redistributions at 24 h post-KSHV reactivation. We suggest a model in which loci
      are held in an unfavorable chromatin architecture and "spring" to a transient
      intermediate state directed by DNA sequence information. We propose that DNA
      sequence plays a more considerable role in the regulation of nucleosome positions
      than was previously appreciated. The surprising findings that nucleosome
      redistributions are widespread, transient, and DNA-directed shift the current
      perspective regarding regulation of nucleosome distribution in humans. 

PMID- 24310003
TI  - Salivary signals of European corn borer induce indirect defenses in tomato.
AB  - Plants can recognize the insect elicitors and activate its defense mechanisms.
      European Corn Borer (ECB; Ostrinia nubilalis) saliva, produced from the labial
      salivary glands and released through the spinneret, is responsible for inducing
      direct defenses in host plants. Glucose oxidase (GOX) present in the ECB saliva
      induced direct defenses in tomato. By contrast, GOX activity in ECB saliva was
      insufficient to trigger defenses in maize, suggesting that host-specific salivary
      elicitors are responsible for inducing direct defenses in host plants. Our
      current study further examined whether ECB saliva can trigger indirect defenses
      in tomato. Relative expression levels of TERPENE SYNTHASE5 (TPS5) and
      HYDROPEROXIDE LYASE (HPL), marker for indirect defenses in host plants, were
      monitored. Quantitative real-time PCR analysis revealed that ECB saliva can
      induce the expression of TPS5 and HPL, suggesting that salivary signals can
      induce indirect defenses in addition to the direct defenses. Further experiments
      are required to identify different ECB elicitors that are responsible for
      inducing direct and indirect defenses in host plants. 

PMID- 24310002
TI  - Systematic mapping of occluded genes by cell fusion reveals prevalence and
      stability of cis-mediated silencing in somatic cells.
AB  - Both diffusible factors acting in trans and chromatin components acting in cis
      are implicated in gene regulation, but the extent to which either process
      causally determines a cell's transcriptional identity is unclear. We recently
      used cell fusion to define a class of silent genes termed "cis-silenced" (or
      "occluded") genes, which remain silent even in the presence of trans-acting
      transcriptional activators. We further showed that occlusion of lineage
      inappropriate genes plays a critical role in maintaining the transcriptional
      identities of somatic cells. Here, we present, for the first time, a
      comprehensive map of occluded genes in somatic cells. Specifically, we mapped
      occluded genes in mouse fibroblasts via fusion to a dozen different rat cell
      types followed by whole-transcriptome profiling. We found that occluded genes are
      highly prevalent and stable in somatic cells, representing a sizeable fraction of
      silent genes. Occluded genes are also highly enriched for important developmental
      regulators of alternative lineages, consistent with the role of occlusion in
      safeguarding cell identities. Alongside this map, we also present whole-genome
      maps of DNA methylation and eight other chromatin marks. These maps uncover a
      complex relationship between chromatin state and occlusion. Furthermore, we found
      that DNA methylation functions as the memory of occlusion in a subset of occluded
      genes, while histone deacetylation contributes to the implementation but not
      memory of occlusion. Our data suggest that the identities of individual cell
      types are defined largely by the occlusion status of their genomes. The
      comprehensive reference maps reported here provide the foundation for future
      studies aimed at understanding the role of occlusion in development and disease. 

PMID- 24310005
TI  - Editorial.

PMID- 24310004
TI  - Primary fibroblast cultures and karyotype analysis for the olive ridley sea
      turtle (Lepidochelys olivacea).

PMID- 24310006
TI  - Reminiscence about'Chloropseudomonas ethylicum' and the FMO-protein.
AB  - In 1961 the green sulfur bacterium-containing mixed culture known
      as'Chloropseudomonas ethylicum' was brought to Brookhaven National Laboratory
      (USA) from Moscow State University (USSR). The water-soluble bacteriochlorophylla
      protein (FMO-protein) was extracted, purified and characterized by absorption and
      circular dichroism spectroscopy, by X-ray crystallography and by primary
      structure determination. 

PMID- 24310007
TI  - Reflections onChloroflexus.
AB  - A personal historic account is presented of the discovery of the anoxygenic
      filamentous bacteria of hot springs:Heliothrix oregonensis andChloroflexus
      aurantiacus. The later discoveries of marine and hypersaline forms are also
      described. 

PMID- 24310008
TI  - Discovery of the heliobacteria.
AB  - The first photosynthetic bacterium obtained in pure culture wasRhodospirillum
      rubrum, isolated by Erwin Esmarch in 1887. The organism appeared to be an aerobic
      heterotroph, and Esmarch was unaware of its photosynthetic capability. The
      overall general characteristics of a number of major species of photosynthetic
      bacteria were described by Molisch and van Niel before 1945. Subsequently, our
      knowledge of the anoxygenic phototrophs increased greatly through the systematic
      study of numerous new species isolated from enrichment cultures in which capacity
      for anaerobic (and anoxygenic) growth with light as the energy source was a
      primary selective factor. A further refinement of the enrichment technique
      required ability to use N2 as the sole source of nitrogen for growth under
      anaerobic photosynthetic conditions, and this led to the isolation of additional
      new species, including the heliobacteria. The first recognition of the
      heliobacteria was facilitated by serendipity, which was a significant factor in a
      number of other researches on photosynthetic bacteria (Gest 1992). 

PMID- 24310009
TI  - Nomenclature of the bacteriochlorophyllsc,d, ande.
AB  - A system for nomenclature of the various homologues of the
      bacteriochlorophyllsc(1),d(2), ande(3) is presented. 

PMID- 24310010
TI  - Gene nomenclature recommendations for green photosynthetic bacteria and
      heliobacteria.
AB  - Recommendations are given for naming of genes coding for reaction center, antenna
      and electron transport proteins in green photosynthetic bacteria and
      heliobacteria. 

PMID- 24310011
TI  - Oscillochloris trichoides neotype strain DG-6.
AB  - The new strain of filamentous green bacterium strain DG-6 was isolated in pure
      culture from the spring of Caucuses. The study of this bacterium allows to
      suggest that it is a member of the familyChloroflexaceae and may be considered
      asOscillochloris trichoides neotype strain. The description of this green
      bacterium is given. 

PMID- 24310012
TI  - Chloroflexus-like organisms from marine and hypersaline environments:
      Distribution and diversity.
AB  - We report the presence of a diverse number ofChloroflexus-like organisms in
      intertidal marine and submerged hypersaline microbial mats using light, infrared
      fluorescence, and electron microscopy. The intertidal organisms appear
      morphologically very similar to thermophilicC. aurantiacus while the 2
      hypersaline strains are larger and have a more complex ultrastructure composed of
      chlorosome-bearing internal membranes that appear to arise as invaginations of
      the cell membrane. By comparing spectroradiometry of microbial mat layers with
      microscopic observations, we have confirmed that theChloroflexus-like organisms
      are major constituents of the hypersaline microbial mat communities. In situ
      studies on mat layers dominated byChloroflexus-like organisms showed that sulfide
      dependent photoautotrophic activity sustained by near infrared radiation
      prevailed. Autoradiographic analyses revealed that autotrophy was sustained in
      the filaments by 750 nm radiation. Three morphologically distinct strains are now
      maintained in mixed culture. One of these appears to be growing
      photoautotrophically. 

PMID- 24310013
TI  - Effects of light quality on the physiology and the ecology of planktonic green
      sulfur bacteria in lakes.
AB  - The effect of light quality on the selection of natural populations of Green
      Sulfur Bacteria (Chlorobiaceae) is considered to be a classic factor in the
      determination of their ecological niches. From the comparison among phototrophic
      bacterial populations of lakes, it is shown that brown and green pigmented groups
      of Chlorobiaceae have a differential distribution depending on depth. Statistical
      analyses prove that green species, which dominate at shallow oxic/anoxic
      boundaries, are correlated to light spectra enriched in long wavelengths, while
      brown ones are found when light spectra are enriched in the central region of the
      spectrum, as in deeper lake layers. Physiological experiments have been made
      withChlorobium limicola andC. phaeobacteroides cultures placed under different
      light quality conditions, in order to verify these hypotheses made on a field
      data basis. Results show that red and white light has more positive effects on
      the green bacterium than on the brown. Blue and green light illuminations have
      opposite consequences. Therefore, the effect of shallow depths and Chromatiaceae
      shading-which also increases the proportion of long wavelengths in light spectra
      benefits the bacteriochlorophyll-based strategies of green species. On the other
      hand, the carotenoid-based strategies of brown ones are favored by the light
      climates usually dominant at greater depths. Thus, brown species are considered
      to be singular adaptations of Chlorobiaceae to depth, where bacteriochlorophyll
      light-harvesting is strongly limited by light quality. 

PMID- 24310014
TI  - Lipids of heliobacteria are characterised by a high proportion of monoenoic fatty
      acids with variable double bond positions.
AB  - The fatty acid composition and lipid pattern of six strains of heliobacteria have
      been analysed. The results were fairly uniform for all strains. Phosphatidyl
      ethanolamine and phosphatidyl glycerol were the dominating lipids found, with the
      former as the major one. No glycolipids were detected. The general fatty acid
      pattern was dominated by acids of chain length C16 to C18. An unusually large
      proportion of monoenoic acids was seen, with up to four positional isomers for
      each chain length. Methyl branched (iso) fatty acids were present, but not
      cyclopropyl or hydroxy fatty acids nor fatty alcohols. 

PMID- 24310015
TI  - An enzyme and(13)C-NMR study of carbon metabolism in heliobacteria.
AB  - Heliobacteria are a group of anoxygenic phototrophs that can grow
      photoheterotrophically in defined minimal media on only a limited range of
      organic substrates as carbon sources. In this study the mechanisms which operate
      to assimilate carbon and the routes employed for the biosynthesis of cellular
      intermediates were investigated in a newHeliobacterium strain, HY-3. This was
      achieved using two approaches (1) by measuring the activities of key enzymes in
      cell-free extracts and (2) by the use of(13)C nuclear magnetic resonance (NMR)
      spectroscopy to analyze in detail the labelling pattern of amino-acids of cells
      grown on [(13)C] pyruvate and [(13)C] acetate.Heliobacterium strain HY-3 was
      unable to grow autotrophically on CO2/H2 and neither (ATP)-citrate lyase nor
      ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBPcase) were detectable in
      cell-free extracts. The enzyme profile of pyruvate grown cells indicated the
      presence of a pyruvate:acceptor oxidoreductase at high specific activity which
      could convert pyruvate to acetyl-Coenzyme A. No pyridine nucleotide dependent
      pyruvate dehydrogenase complex activity was detected. Of the citric-acid cycle
      enzymes, malate dehydrogenase, fumarase, fumarate reductase and an NADP-specific
      isocitrate dehydrogenase were readily detectable but no aconitase or citrate
      synthase activity was found. However, the labelling pattern of glutamate in long
      term 2-[(13)C] acetate incorporation experiments indicated that a mechanism
      exists for the conversion of carbon from acetyl-CoA into 2-oxoglutarate. A 2
      oxoglutarate:acceptor oxidoreductase activity was present which was also
      assayable by isotope exchange, but no 2-oxoglutarate dehydrogenase complex
      activity could be detected. Heliobacteria appear to use a type of incomplete
      reductive carboxylic acid pathway for the conversion of pyruvate to 2
      oxoglutarate but are unable to grow autotrophically using this metabolic route
      due to the absence of ATP-citrate lyase. 

PMID- 24310016
TI  - Low-temperature spectroscopy of isolated FMO-protein and a membrane-free reaction
      center complex from the green sulfur bacteriumChlorobium tepidum.
AB  - We have isolated the water-soluble BChla-protein (FMO-protein) from the greer
      sulfur bacteriumChlorobium tepidum by a new procedure involving a salt-wash of
      isolated membranes at alkaline pH. The absorption spectrum of the isolated FMO
      protein at 77 K was compared with that of a reaction-center complex containing
      the FMO-protein (FMO-RC complex) isolated fromC. tepidum following the procedure
      of Feiler U, Nitsche W and Michel H (1992) Biochemistry 31: 2608-2614. Oxidation
      or illumination of the FMO-RC complex caused bleaching of a component with a
      maximum at 836 nm which was not present in the purified FMO-protein. 

PMID- 24310017
TI  - Iron-sulfur centers in the photosynthetic reaction center complex fromChlorobium
      vibrioforme. Differences from and similarities to the iron-sulfur centers in
      Photosystem I.
AB  - The photosynthetic reaction center complex from the green sulfur
      bacteriumChlorobium vibrioforme has been isolated under anaerobic conditions.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals polypeptides
      with apparent molecular masses of 80, 40, 30, 18, 15, and 9 kDa. The 80- and 18
      kDa polypeptides are identified as the reaction center polypeptide and the
      secondary donor cytochromec 551 encoded by thepscA andpscC genes, respectively. N
      terminal amino acid sequences identify the 40-kDa polypeptide as the
      bacteriochlorophylla-protein of the baseplate (the Fenna-Matthews-Olson protein)
      and the 30-kDa polypeptide as the putative 2[4Fe-4S] protein encoded bypscB.
      Electron paramagnetic resonance (EPR) analysis shows the presence of an iron
      sulfur cluster which is irreversibly photoreduced at 9K. Photoaccumulation at
      higher temperature shows the presence of an additional photoreduced cluster. The
      EPR spectra of the two iron-sulfur clusters resemble those of FA and FB of
      Photosystem I, but also show significantly differentg-values, lineshapes, and
      temperature and power dependencies. We suggest that the two centers are
      designated Center I (with calculatedg-values of 2.085, 1.898, 1.841), and Center
      II (with calculatedg-values of 2.083, 1.941, 1.878). The data suggest that
      Centers I and II are bound to thepscB polypeptide. 

PMID- 24310018
TI  - Photo-oxidation of membrane-bound and soluble cytochromec in the green sulfur
      bacteriumChlorobium tepidum.
AB  - We studied the photosynthetic electron transfer system of membrane-bound and
      soluble cytochromec inChlorobium tepidum, a thermophilic green sulfur bacterium,
      using whole cells and membrane preparations. Sulfide and thiosulfate,
      physiological electron donors, enhanced flash-induced photo-oxidation ofc-type
      cytochromes in whole cells. In membranes,c-553 cytochromes with two (or three)
      heme groups served as immediate electron donors for photo-oxidized
      bacteriochlorophyll (P840) in the reaction center, and appeared to be closely
      associated with the reaction center complex. The membrane-bound cytochromec-553
      had anE m-value of 180 mV. When isolated soluble cytochromec-553, which has an
      apparent molecular weight of 10 kDa and seems to correspond to the cytochromec
      555 inChlorobium limicola andChlorobium vibrioforme, was added to a membrane
      suspension, rapid photo-oxidation of both soluble and membrane-bound cytochromesc
      553 was observed. The oxidation of soluble cytochromec-553 was inhibited by high
      salt concentrations. In whole cells, photo-oxidation was observed in the absence
      of exogenous electron donors and re-reduction was inhibited by stigmatellin, an
      inhibitor of the cytochromebc complex. These results suggest that the role of
      membrane-bound and soluble cytochromec inC. tepidum is similar to the role of
      cytochromec in the photosynthetic electron transfer system of purple bacteria. 

PMID- 24310019
TI  - Photosynthetic electrogenic events in native membranes ofChloroflexus
      aurantiacus. Flash-induced charge displacements within the reaction center
      cytochromec 554 complex.
AB  - The thermophilic phototrophChloroflexus aurantiacus possesses a photosynthetic
      reaction center (RC) containing a pair of menaquinones as primary (QA) and
      secondary (QB) electron acceptors and a bacteriochlorophyll dimer (P) as a
      primary donor. A tetraheme cytochromec 554 with two high(H)- and two low(L)
      potential hemes operates as an immediate electron donor for P. The following
      equilibrium Em,7 values were determined by ESR for the hemes in whole membrane
      preparations: 280 mV (H1), 150 mV (H2), 95 mV (L1) and 0 mV (L2) (Van Vliet et
      al. (1991) Eur. J. Biochem. 199: 317-323). Partial electrogenic reactions induced
      by a laser flash inChl. aurantiacus chromatophores adsorbed to a phospholipid
      impregnated collodion film were studied electrometrically at pH 8.3. The
      photoelectric response included a fast phase of DeltaPsi generation (tau < 10 ns,
      phase A). It was ascribed to the charge separation between P(+) and QA (-) as its
      amplitude decreased both at high and low Eh values (Em,high=360+/-10 mV,
      estimated Em,low~?s-160 mV) in good agreement with Em values for P/P(+) and QA/QA
      (-) redox couples. A slower kinetic component appeared upon reduction of the
      cytochromec 554 hemes (phase C). With H1 reduced before the flash the amplitude
      of phase C was equal to 15-20% of that of phase A and its rise time was 1.2-1.3
      MUs: we attribute this phase to the electrogenic electron transfer from H1 to
      P(+). Pre-reduction of H2 decreased the tau value to about 700-800 ns and
      increased the amplitude of phase C to 30-35% of that of phase A. Pre-reduction of
      L1 further accelerated phase C (up to tau of 500 ns) and induced a reverse
      electrogenic phase with tau of 12 MUs and amplitude equal to 10% of phase A. Upon
      pre-reduction of L2 the rise time of phase C was decreased to about 300 ns and
      its amplitude decreased by 30%. The acceleration in the onset of phase C is
      explained by the acceleration of the rate-limiting H1 => P electrogenic reaction
      after reduction of the other hemes due to their electrostatic influence; a P-H1
      (L1-L2)-H2 alignment of redox centers with an approximately rhombic arrangement
      of the cytochromec 554 hemes is proposed. The observed reverse phase is ascribed
      to the post-flash charge redistribution between the hemes. Redox titration of the
      amplitude of phase C yielded the Em,8.3 values of H1, H2 and L2 hemes: 340+/-10
      mV for H1, 160+/-20 mV for H2 and -40+/-40 mV for L2. 

PMID- 24310020
TI  - Bacteriochlorophyllc formation and chlorosome development inChloroflexus
      aurantiacus.
AB  - The dependence of chlorosome development on bacteriochlorophyll (BChl)c synthesis
      was studied with the phototrophic green bacteriumChloroflexus aurantiacus. By
      selecting defined culture conditions, three possibilities could be identified.
      Upon addition of 5-aminolevulinic acid, cells of resting cultures increased their
      specific BChlc contents as well as the volumes of already existing chlorosomes.
      The number of chlorosomes, however, remained constant. Serine-limited chemostat
      cultures grown under steady state conditions exhibited constant rates of
      synthesis of both BChlc as well as of chlorosomes. The volume of the latter
      remained constant, as well. Upon addition of ALA to chemostat cultures,
      chlorosomes were synthesized at the same rate as before but their volumes
      increased as a consequence of increased BChlc incorporation. In chlorosomes
      isolated from resting cultures supplied with ALA the amounts of all of the
      polypeptides increased only slightly, if at all. Moreover, the ratio of all of
      the chlorosomal polypeptides remained largely constant. These results show that
      chlorosomes may incorporate newly synthesized BChlc without concomitant formation
      of chlorosomal polypeptides. This means that there was no obvious coordination of
      polypeptide and BChlc synthesis. On this basis, it appears unlikely that one of
      the chlorosomal polypeptides functions as an apoprotein of a presumed BChlc
      holochrome complex. 

PMID- 24310021
TI  - Effects of illumination intensity on bacteriochlorophyllc homolog distribution
      inChloroflexus aurantiacus grown under controlled conditions.
AB  - Green photosynthetic bacteria contain a mixture of stereoisomers and homologs of
      their major light harvesting pigment, bacteriochlorophyll (BChl)c. We have
      determined the distribution of photosynthetic pigments in the green filamentous
      bacteriumChloroflexus aurantiacus grown in turbidostat culture under light
      limited conditions at 5 different illumination intensities. Pigments were
      extracted from isolated cells, analyzed by HPLC, and the homologs of BChlc
      identified by their mass spectra. The ratio between BChlc, BChla and carotenoid
      remained constant at low illumination intensities; at higher intensities BChla
      and carotenoid increased in parallel compared to BChlc. The BChlc homolog
      distribution changed even under conditions where the ratio of the total amount to
      the other pigments was unchanged, but there were no evidence for a constant
      stoichiometric ratio between any pair of homologs. 

PMID- 24310022
TI  - Separation of bacteriochlorophyll homologues from green photosynthetic sulfur
      bacteria by reversed-phase HPLC.
AB  - A reversed-phase High Performance Liquid Cromatography (HPLC) method has been
      developed to accurately separate bacteriochlorophyllsc, d ande homologues in a
      reasonably short run time of 60 minutes. By using this method, two well-defined
      groups of bacteriochlorophyll homologue peaks can be discriminated. The first one
      consists of 4 peaks (min 24 to 30), which corresponds to the four main farnesyl
      homologues. The second peak subset is formed by a cluster of up to 10 minor peaks
      (min 33 to 40). These peaks can be related with series of several alcohol esters
      of the different chlorosome chlorophylls. The number of homologues was, however,
      quite variable depending on both, the bacteriochlorophyll and the bacterial
      species. The method hereby described, also provides a good separation of other
      photosynthetic pigments, either bacterial (Bacteriochlorophylla, chlorobactene,
      isorenieratene and okenone) or algal ones (Chlorophylla, Pheophytina and beta
      carotene). A preliminary screening of the homologue composition of several green
      photosynthetic bacterial species and isolates, has revealed different relative
      quantitative patterns. These differences seem to be related to physiological
      aspects rather than to taxonomic ones. The application of the method to the study
      of natural populations avoids the typical drawbacks on the pigment identification
      of overlapping eukaryotic and prokaryotic phototrophic microorganisms, giving
      further information about their physiological status. 

PMID- 24310023
TI  - Giant circular dichroism of chlorosomes fromChloroflexus aurantiacus treated with
      1-hexanol and proteolytic enzymes.
AB  - The circular dichroism (CD) spectrum of isolated chlorosomes fromChloroflexus
      aurantiacus showed a conservative, S-shaped signal with a negative maximum at 723
      nm, a positive maximum at 750 nm and a zero-crossing at 740 nm. Proteolytic
      treatment of chlorosomes with trypsin at 37 degrees C did not change the CD
      signal or the absorption spectrum in contrast to treatment with proteinase K,
      where a twofold increase in rotational strength and a slight decrease of the
      absorption band at 740 nm were observed. Treatment with saturating 1-hexanol
      concentrations resulted in a blue shift of the absorption band at 740 nm as well
      as in changes of the CD spectrum. These changes reversed when the sample was
      diluted to half the saturating 1-hexanol concentration. In contrast to that, we
      observed an irreversible formation of a giant CD signal using the combination of
      1-hexanol and proteinase K treatment. Electron micrographs of chlorosomes treated
      with both 1-hexanol and proteinase K showed large aggregates of multiple
      chlorosome size. By comparison of proteinase K induced effects with trypsin
      effects it appeared that the 5.7 kDa polypeptide has a structural role in the
      organisation of BChlc in the chlorosome. 

PMID- 24310024
TI  - Pigment interactions in chlorosomes of various green bacteria.
AB  - Resonance Raman experiments were performed on different green bacteria. With blue
      excitation, i.e. under Soret resonance or preresonance conditions, resonance
      Raman contributions were essentially arising from the chlorosome pigments. By
      comparing these spectra and those of isolated chlorosomes, it is possible to
      evaluate how the latter retain their native structure during the isolation
      procedures. The structure of bacteriochlorophyll oligomers in chlorosomes was
      interspecifically compared, in bacteriochlorophyllc- and bacteriochlorophylle-
      synthesising bacteria. It appears that interactions assumed by the 9-keto
      carbonyl group are identical inChlorobium limicola, Chlorobium tepidum,
      andChlorobium phaeobacteroides. In the latter strain, the 3-formyl carbonyl group
      of bacteriochlorophylle is kept free from intermolecular interactions. By
      contrast, resonance Raman spectra unambiguously indicate that the structure of
      bacteriochlorophyll oligomers is slightly different in chlorosomes
      fromChloroflexus auranticus, either isolated or in the whole bacteria. 

PMID- 24310025
TI  - Molecular organization of bacteriochlorophyll in chlorosomes of the green
      photosynthetic bacteriumChloroflexus aurantiacus: Studies of fluorescence
      depolarization accompanied by energy transfer processes.
AB  - Examination was made of changes in fluorescence polarization plane by energy
      transfer in the chlorosomes of the green photosynthetic bacterium,Chloroflexus
      aurantiacus. Fluorescence anisotropy in the picosecond (ps) time region was
      analyzed using chlorosomes suspended in solution as well as those oriented in a
      polyacrylamide gel. When the main component of BChlc was preferentially excited,
      the decay of fluorescence anisotropy was found to depend on wavelength. In the
      chlorosome suspension, the anisotropy ratio of BChlc changed from 0.31 to 0.24
      within 100 ps following excitation. In the baseplate BChla region, this ratio
      decreased to a negative value (-0.09) from the initial 0.14. In oriented samples,
      the degree of polarization remained at 0.68 for BChlc, and changed from 0.25 to 
      0.40 for the baseplate BChla by excitation light whose electric vector was
      parallel to the longest axis of chlorosomes. In the latter case, there was a
      shift from 0.30 to -0.55 by excitation perpendicular to the longest axis. Time
      resolved fluorescence polarization spectra clearly indicated extensive changes in
      polarization plane accompanied by energy transfer. The directions of polarization
      plane of emission from oriented samples were mostly dependent on chlorosome
      orientation in the gel but not on that of the polarization plane of excitation
      light. Orientations of the dipole moment of fluorescence components was
      consistent with that of absorption components as determined by the linear
      dichroism (Matsuura et al. (1993) Photochem. Photobiol. 57: 92-97). A model for
      molecular organization of BChlc anda in chlorosomes is proposed based on
      anisotropic optical properties. 

PMID- 24310026
TI  - Chlorosomes of green sulfur bacteria: Pigment composition and energy transfer.
AB  - The pigment composition and energy transfer pathways in isolated chlorosomes
      ofChlorobium phaeovibrioides andChlorobium vibrioforme were studied by means of
      high performance liquid chromatography (HPLC) and picosecond absorbance
      difference spectroscopy. Analysis of pigment extracts of the chlorosomes revealed
      that they contain small amounts of bacteriochlorophyll (BChl)a esterified with
      phytol, whereas the BChlsc, d ande are predominantly esterified with farnesol.
      The chlorosomal BChla content inC. phaeovibrioides andC. vibrioforme was found to
      be 1.5% and 0.9%, respectively. The time resolved absorbance difference spectra
      showed a bleaching shifted to longer wavelengths as compared to the Qy absorption
      maxima and in chlorosomes ofC. vibrioforme also an absorbance increase at shorter
      wavelengths was observed. These spectral features were ascribed to excitation of
      oligomers of BChle and BChlc/d, respectively. 'One-color' and 'two-color' pump
      probe kinetics ofC. phaeovibrioides showed rapid energy transfer to long
      wavelength absorbing BChle oligomers, followed by trapping of excitations by
      BChla with a time constant of about 60 ps. Time resolved anisotropy measurements
      inC. vibrioforme showed randomization of excitations among BChla molecules with a
      time constant of about 20 ps, indicating that BChla in the baseplate is organized
      in clusters. One-color and two-color pump-probe measurements inC. vibrioforme
      showed rapid energy transfer from short-wavelength to long-wavelength absorbing
      oligomers with a time constant of about 11 ps. Trapping of excitations by BChla
      in this species could not be resolved unambiguously due to annihilation processes
      in the BChla clusters, but may occur with time constants of 15, 70 and 200 ps. 

PMID- 24310027
TI  - Strongly exciton-coupled BChle chromophore system in the chlorosomal antenna of
      intact cells of the green bacteriumChlorobium phaeovibrioides: A spectral hole
      burning study.
AB  - Spectral hole burning studies of intact cells of the green bacteriumChlorobium
      phaeovibrioides have proven that the Qy-absorption system of antenna
      bacteriochlorophylle (BChle) should be interpreted in terms of the delocalized
      exciton level structure of an aggregate. For the first time the 0-0 band of the
      lowest exciton state of BChle aggregates has been directly detected as the lowest
      energy inhomogeneously broadened band (FWHM ~ 100 cm(-1); position of maximum, at
      ~ 739 nm) of the near-infrared BChle band in the 1.8 K excitation spectrum
      (FWHM=750 cm(-1); position of maximum, at 715 nm). The comparative analysis of
      the hole spectra, measured for the three species of BChlc- ande-containing green
      bacteria, has shown that the 0-0 transition bands of the lowest exciton state of
      BChlc ande aggregates display fundamentally similar spectral features: (1) the
      magnitude of inhomogeneous broadening of these bands is about 100 cm(-1); (2) at
      the wavelength of the maximum of each band, the amplitude of the preburnt
      excitation spectrum makes up 20% of the maximum amplitude of the spectrum; (3)
      the spectral position of each band coincides with the spectral position of the
      longest wavelength band of the circular dichroism spectrum; (4) the width of
      these bands is ~ 2.3-times less than that of monomeric BChl in vitro. 

PMID- 24310028
TI  - Structures of chlorosomes and aggregated BChlc inChlorobium tepidum from solid
      state high resolution CP/MAS(13)C NMR.
AB  - Cross polarization/magic angle spinning (CP/MAS)(13)C (solid state high
      resolution) NMR spectra were observed for chlorosomes and BChlc aggregates.
      Similarity of both kinds of spectra (except for some signals assignable to
      proteins and lipids in chlorosomes) indicates that BChlc's in chlorosomes are
      present just as in synthetic BChlc aggregates. Chemical shifts for C13(1)
      carbonyl and C3(1) hydroxylethyl carbons indicate hydrogen bonding between them.
      Comparison of solution and solid state(13)C NMR chemical shifts shows the five
      coordinated nature of BChlc aggregates. Some chemical shift differences were
      attributable to ring currents shifts. Their comparisons with calculated ring
      current shift values predicted structures for the aggregates. Cross polarization
      dynamics of the CP/MAS(13)C NMR signals explored dynamic and structural nature of
      the BChlc aggregates. 

PMID- 24310029
TI  - On the structure of bacteriochlorophyll molecular aggregates in the chlorosomes
      of green bacteria. A molecular modelling study.
AB  - The supramolecular structure of methyl (3(1) R)-BChlided aggregation has been
      explored by molecular modelling in order to elucidate the unusual structure of
      the BChl rods in the chlorosomal antennae of green bacteria. The aggregate
      construction progressed from a BChlide monomer in 5c coordination which was
      stepwise combined to form trimeric, pentameric and decameric chlorin stacks, all
      incorporating Mg....O-H as a basic interaction element which links two chlorins
      between the 3(1)-hydroxyl oxygen and the Mg. Up to the level of the trimer, the
      structures were optimized by both a semiempirical quantum chemical method (PM3)
      and a force field method, while larger structures were only modelled by the force
      field (MM+). Strong interactions were found by extended stacking of chlorins
      which are in van der Waals contact. Extended hydrogen bonding networks upon stack
      pairing brought about by OH....O=C bonds (bond length ca. 2.2A, angle 139-153
      degrees ) between appropriately situated chlorin pairs and by electrostatic
      interactions lead to very large energy stabilizations. The structural features of
      a modelled 40mer BChl aggregate are in full accord with all spectroscopic and low
      resolution structural information on the in-vitro and chlorosomal BChl
      aggregates. Most important, from the rotation angle between stacks of ca. 16
      degrees  and the stack-to-stack distance of 7.6 A a tubular structure can be
      extrapolated to form on further extension of the aggregate. It has a predicted
      diameter of about 5.4 nm (Mg-Mg distance), i.e. very similar to that found for
      the rod elements in the chlorosomes ofChloroflexus. 

PMID- 24310030
TI  - The formation and characterization of the in vitro polymeric aggregates of
      bacteriochlorophyllc homologs fromChlorobium limicola in aqueous suspension in
      the presence of monogalactosyl diglyceride.
AB  - Artificial aggregates of bacteriochlorophyllc (BChlc) were formed in an aqueous
      medium in the presence of a lipid, monogalactosyl diglyceride (MGDG), and the
      optical properties of those aggregates were studied by absorption and circular
      dichroism (CD) mainly. Four BChlc homologs, ([E,E]BChlc F, [P,E]BChlc F,
      [E,M]BChlc F and [I,E]BChlc F), were isolated from the green photosynthetic
      bacteriumChlorobium limicola strain 6230. Above 0.0004%, MGDG induced a red-shift
      of the absorption maxima of BChlc aggregates. At 0.003% MGDG BChlc aggregates
      showed absorption maxima in the range of 724 to 745 (+/-3) nm with a shift of 12
      to 24 (+/-3) nm depending on the homolog species. Four kinds of BChlc-MGDG
      aggregates showed characteristic CD spectra. [E,M]BChlc F gave rise to a CD
      spectrum similar to that of chlorosomes, while the other three gave spectra of
      opposite sign. These aggregates are sensitive to 1-hexanol treatment; in a
      saturating amount (0.85%) of 1-hexanol, all the homologs gave a monomer-like
      absorption spectrum peaking at 670nm. At an intermediate concentration (0.5%),
      [E,M]BChlc F showed an enhanced CD intensity, as observed in native chlorosomes.
      Resonance Raman spectra of the monomer-like BChlc samples indicated that the keto
      vibrational band at ca. 1640 cm(-1) was considerably weakened by the 0.85% 1
      hexanol treatment, however the 1680 cm(-1) band characteristic of a free keto
      group did not appear. These results indicate that the artificial aggregates
      formed by purified BChlc homologs and MGDG are good models for studying
      chlorosomes structure. 

PMID- 24310031
TI  - Dimerization of synthetic zinc aminochlorins in non-polar organic solvents.
AB  - UV-visible spectra of synthetic zinc aminochlorins were measured in 99:1 (v/v)
      cyclohexane-dichloromethane solution. The compounds formed anti-parallel dimers
      with mutual coordination of the central zinc in one molecule to the amino
      nitrogen in the other (Qy band red-shift of about 500 cm(-1)). Such a dimer
      arrangement appears to be too stable to form far-red (> 1500 cm(-1)) shifted
      oligomers which have been observed with bacteriochlorophylls-c (possessing a
      hydroxy group and a central magnesium) and with their model compounds (with a
      hydroxy group and a central zinc) in non-polar organic solvents. 

PMID- 24310032
TI  - A gene cluster inChlorobium vibrioforme encoding the first enzymes of chlorophyll
      biosynthesis.
AB  - A cloned 5.8-kb genomic fragment of the green sulfur bacteriumChlorobium
      vibrioforme encodes the genes for three enzymes catalyzing early steps in the
      biosynthetic pathway of tetrapyrroles, common to chlorophyll and heme. ThehemA,
      hemC andhemD genes encode the enzymes glutamyl tRNA dehydrogenase,
      porphobilinogen deaminase and uroporphyrinogen III synthase, respectively. The
      cloned genes were expressed in transformedEscherichia coli orSalmonella
      typhimurium and conferred autotrophy on the respective auxotrophs. Activities of
      the enzymes encoded by the cloned genes were demonstrated in vitro, with cell
      extracts obtained from the transformed enterobacteria. The proximity of these
      genes indicates that they form a cluster inChlorobium vibrioforme, while in most
      other organisms they appear to be scattered. The presence of this cluster may
      imply coordinate regulation of the genes involved and they may constitute an
      operon. 

PMID- 24310033
TI  - Genes encoding two chlorosome components from the green sulfur bacteriaChlorobium
      vibrioforme strain 8327D andChlorobium tepidum.
AB  - Chlorosomes of the thermophilic green sulfur bacteriumChlorobium tepidum have
      been isolated and their polypeptides analyzed by polyacrylamide gel
      electrophoresis and amino acid sequencing. These chlorosomes were shown to
      contain nine different polypeptides ranging in mass from approximately 6 to 27
      kDa. ThecsmA gene, encoding a highly abundant chlorosome protein with a mass of
      6.2 kDa, were cloned and sequenced from bothChlorobium vibrioforme strain 8327D
      andChlorobium tepidum. The gene from both species predicts identical proteins of
      79 amino acid residues, and a comparison of the deduced sequence with that
      determined for the protein indicates that 20 amino acid residues are post
      translationally removed from the carboxyl-terminus of the CsmA precursor.
      Transcript analyses showed that inChlorobium tepidum thecsmA gene is encoded on
      two transcripts of approximately 350 and 940 nucleotides; the smaller transcript
      probably results from processing of the larger RNA molecule. Transcription of the
      longer mRNA initiates 68 basepairs upstream from the start codon of a second open
      reading frame that is located 154 nucleotides 5' tocsmA and that predicts a
      protein of 139 amino acid residues. The amino-terminal sequence determined for a
      14.5 kDa polypeptide in the chlorosomes ofChlorobium tepidum matched the sequence
      deduced from this open reading frame except for the absence of the initiator
      methionine residue; accordingly, this gene has been namedcsmC. A comparison of
      the genomic organization of thecsmA loci inChlorobium vibrioforme, Chlorobium
      tepidum, andChloroflexus aurantiacus were found to be surprisingly similar. 

PMID- 24310034
TI  - Highly efficient integration of foreign DNA into the genome of the green sulfur
      bacterium,Chlorobium vibrioforme by homologous recombination.
AB  - Highly efficient and reproducible transformation ofChlorobium vibrioforme with
      plasmid DNA has been achieved by electroporation. Specific parameters have been
      optimized for the electrotransformation procedure. The method was developed using
      a construct containing a full copy of thepscC gene encoding the cytochromec 551
      subunit of the photosynthetic reaction center complex and theaadA gene encoding
      streptomycin resistance as selectable marker. Southern blotting analysis showed
      that the tested colonies were true transformants with the plasmid integrated into
      the genome by single homologous recombination. No transformants were obtained
      using the vector without thepscC gene showing that this vector does not replicate
      inC. vibrioforme. Thus transformation is possible only by homologous
      recombination. When using constructs designed to inactivate thepscC gene by
      insertion no transformants were obtained, indicating that the gene is
      indispensable for growth. The vector pVS2 carrying genes for erythromycin and
      chloramphenicol resistance was shown to replicate inC. vibrioforme. The two
      transformations shown here, provide an important genetical tool in the further
      analysis of structure and function of the photosynthetic apparatus in green
      sulfur bacteria. 

PMID- 24310035
TI  - Evolution of heliobacteria: Implications for photosynthetic reaction center
      complexes.
AB  - The evolutionary position of the heliobacteria, a group of green photosynthetic
      bacteria with a photosynthetic apparatus functionally resembling Photosystem I of
      plants and cyanobacteria, has been investigated with respect to the evolutionary
      relationship to Gram-positive bacteria and cyanobacteria. On the basis of 16S
      rRNA sequence analysis, the heliobacteria appear to be most closely related to
      Gram-positive bacteria, but also an evolutionary link to cyanobacteria is
      evident. Interestingly, a 46-residue domain including the putative sixth membrane
      spanning region of the heliobacterial reaction center protein shows rather strong
      similarity (33% identity and 72% similarity) to a region including the sixth
      membrane-spanning region of the CP47 protein, a chlorophyll-binding core antenna
      polypeptide of Photosystem II. The N-terminal half of the heliobacterial reaction
      center polypeptide shows a moderate sequence similarity (22% identity over 232
      residues) with the CP47 protein, which is significantly more than the similarity
      with the Photosystem I core polypeptides in this region. An evolutionary model
      for photosynthetic reaction center complexes is discussed, in which an ancestral
      homodimeric reaction center protein (possibly resembling the heliobacterial
      reaction center protein) with 11 membrane-spanning regions per polypeptide has
      diverged to give rise to core of Photosystem I, Photosystem II, and of the
      photosynthetic apparatus in green, purple, and heliobacteria. 

PMID- 24310036
TI  - Yield stability and population diversity in oats (Avena sp.).
AB  - The relationship between yield stability and populations containing various
      numbers and combinations of diverse homozygous and homogeneous lines was examined
      in an environment in which considerable variability occurs among and within
      growing seasons. Two groups (1,2), each containing 15 populations (4 pure lines
      grown singly and 11 multilines consisting of mechanical mixtures of all possible
      2,3 and 4 way combinations of these 4 pure lines) were tested in each of 5
      consecutive years. The pure lines in group 1 and 2 were selected on the basis of
      previous yield and yield variability respectively. In group 1, no significant
      differences were found among the 5 year means or the deviation mean squares of
      the 15 populations but highly significant differences among regression
      coefficients were present. The regression coefficients of the 4 pure lines
      differed considerably, indicating that this stability parameter was genetically
      influenced. The regression coefficients of the multilines tended towards unity
      regardless of the regression coefficients of the pure lines involved. In group 2,
      highly significant differences were found among the 5 year means, regression
      coefficients and deviation mean squares of the 15 populations. No consistent,
      predictable pattern was apparent between the mean and stability values of the
      pure lines and the multilines in which they were included. Differences between
      the 2 groups suggest that higher yield and greater stability result in the
      multilines if relatively high yielding pure lines are selected for inclusion. In
      general, the results indicated that multilines containing a number of diverse
      homozygous and homogeneous pure lines have satisfactory yields and enhanced yield
      stability. However, adequate testing of the pure lines and potential multilines
      over a broad range of environments is essential to determine desirable
      combinations. 

PMID- 24310037
TI  - Using regression coefficient as a stability parameter in plant breeding programs.
AB  - Expanding the regression coefficient as stability parameter (Finlay and Wilkinson
      1963) requires an unbiased interpretation of the parameter. Information on the
      covariances among the genotypes of the population must be specific, particularly
      when the assumed relatedness of the genotypes appears questionable. Such a
      problem, however, is not expected when the covariances between the genotypes are
      either zero or equal and possibly non zero. 

PMID- 24310038
TI  - Variations among races of Arabidopsis thaliana (L.) heynh for survival in limited
      carbon dioxide.
AB  - Races of a C3 plant species, Arabidopsis thaliana, were screened for time of
      survival when enclosed in an air-tight chamber with a C4 plant species (Zea mays
      L.). This has been suggested as a method of detecting and selecting for increased
      photosynthetic efficiency among C3 genotypes. The C4 plant should, in such
      conditions, reduce the atmospheric CO2 concentration below the compensation point
      of the C3 plant, resulting in its eventual death. Significant differences were
      found among the A. thaliana races for survival time; some races survived only one
      week in competition with corn while others survived more than two weeks. Two
      races, chosen for contrasting survival in closed chambers, were hybridized and
      compared to their F2 progeny for survival time. Substantial genetic segregation
      occurred among the F2, and a number of transgressive segregates having survival
      times superior of both parents were identified. Also significant heterosis was
      observed in the F2 population. 

PMID- 24310039
TI  - Diallel analysis for some quantitative characters in Petunia hybrida Hort.
AB  - Flowering time, plant height and flower size in Petunia hybrida Hort. (multiflora
      type) have been genetically analysed by means of a 5 * 5 diallel cross. The
      results indicated that: (1) the three characters are controlled by additive
      dominance polygenic systems. The contribution of the additive gene actions to the
      genetic variance of flowering time was relatively higher than that of dominance.
      The reverse situation was found for plant height and flower size. (2) Dominance
      is ambi-directional for the three characters. Ratios of average dominance were in
      the range of partial for flowering-time, complete for plant height and
      overdominance for flower size. (3) Number of genes (or gene groups) controlling
      the characters are about 3, 3 and 5 for flowering time, plant height and flower
      size: respectively, (4) Heritability estimates are 0.84, 0.88 and 0.89 in the
      broad-sense and 0.40, 0.49 and 0.37 in the narrow-sense, for flowering time,
      plant height and flower size; respectively. (5) Heterosis as percent increase of
      the mean F1-hybrid above the higher parent, or decrease below the lower parent,
      was observed for flowering time (+ 9.7% to +13.3%), for plant height (-13.6% to 
      20.3%) and for flower size (+2.5% to +16.0%). 

PMID- 24310040
TI  - Induction of segmental interchanges in pearl millet (Pennisetum typhides).
AB  - Dry seeds of two varieties of Pennisetum typhoides (2n=14), 'Tift 23-B' and 'Bil
      3B', were treated with gamma rays, diethyl sulphate (DES) and ethylene imine (EI)
      at their approximate LD50 dosages and the pollen mother cells of the M1 (first
      generation immediately after the seed treatment) plants were analysed at
      diakinesis for multivalent configurations resulting from segmental interchanges.
      While quadrivalents and trivalents were commonly found in all the mutagenic
      treatments, hexavalents were seen in the gamma-ray treatment only. Ring
      quadrivalents were common in all the treatments and their frequency was higher in
      gamma-ray treatment than in the treatments with the chemical mutagens of which EI
      produced more quadrivalents than DES. The variety 'BIL3B' was more responsive to
      all the mutagens used than 'Tift-23B' in which, excepting in gamma-ray treatment,
      no multivalents were observed in EI and DES treatments.The quadrivalents induced
      by different mutagens were of different types involving different chromosomes,
      indicating some kind of specificity of the mutagens in causing chromosome breaks.
      Thus, in EI-induced quadrivalents the nucleolar chromosome, the shortest
      chromosome of the complement, was involved, whereas in the case of DES and gamma
      rays it was the longest chromosome of the complement that was involved in the
      quadrivalent. Apparently the breaks must have been produced in different
      chromosomes preferentially.Self-pollinated seeds of two heterozygotes whose
      interchanges were induced by EI and gamma rays were given a second cycle
      treatment with gamma rays, again at the LD50 dosage (35 kR), and interchange
      stocks involving different chromosomes, up to a maximum of eight chromosomes were
      realized. Alternate use of EI and gamma rays offered better possibilities of
      obtaining inter-change heterozygotes involving more, if not all, chromosomes in a
      ring than two successive treatments with gamma rays alone. 

PMID- 24310041
TI  - Relative efficiency of North Carolina designs I and II and standard design III in
      three wheat crosses.
AB  - The efficiency of three analyses, namely, Designs I and II of Comstock and
      Robinson (1952) and standard Design III analysis of Kearsey and Jinks (1968), was
      compared in the F2s of three wheat crosses (Norteno 67 x HD 1982, HD 1982 x Moti
      and Sonalika x Moti) for plant height, spikelets per spike and yield per plant.
      The three analyses showed a remarkable agreement in estimating the additive (D)
      component for all three characters in all three crosses. But, as regards the
      estimation of dominance ] (H) component, standard Design III analysis proved to
      be more efficient than the other two analyses in crosses 2 (HD 1982 x Moti) and 3
      (Sonalika x Moti) for all three characters except spikelets per spike in cross 3.

PMID- 24310042
TI  - Gel isoelectric focusing of wheat alcohol dehydrogenase.
AB  - Alcohol dehydrogenase (ADH) of different hexaploid wheat subspecies and varieties
      was investigated by isoelectric focusing in polyacrylamide gels. With this
      technique six ADH isoenzymes can be separated, while by the standard
      electrophoretic technique only three are visible. The ADH pattern revealed by
      isoelectric focusing is in full accordance with the hypothesis that the active
      ADH isozymes in hexaploid wheat are dimers composed of six possible combinations
      of subunits coded by triplicate structural genes. 

PMID- 24310043
TI  - Bioenergetic considerations in the improvement of oil content and quality in oil
      seed crops.
AB  - Production values (PVs), defined as the weight of the end product/weight of the
      substrate required for carbon skeletons and energy production, were calculated
      for plant fatty acids. The PVs varied from 0.361 to 0.300 with linolenic acid
      having the lowest value. In general, the PVs of unsaturated fatty acids were
      lower than those of saturated fatty acids of similar chain lengths. Using this
      basic information, PVs of (A) oils from different oilseed crops, based on their
      standard fatty acid composition and (B) seed biomass with specified oil content
      and fatty acid composition were calculated. 1/PV gives the glucose required for
      the biosynthesis of 1 g end product and thus an estimate of the photosynthate
      requirement for the desired breeding goal can be estimated. Such calculations
      show that increasing oil percentage in seeds has a maximum energy cost when the
      increase in oil is associated with a decrease in the amount of carbohydrates
      where there is no change in protein concentration. Reduction of erucic acid
      content in the rapeseed oil did not alter its PV. It is inferred that there are
      no serious bioenergetic constraints in altering the fatty acid composition. 

PMID- 24310044
TI  - An epidural blood patch causing acute neurologic dysfunction necessitating a
      decompressive laminectomy.
AB  - OBJECTIVES: One risk with placement of an epidural blood patch (EDBP) is spinal
      cord or nerve root compression resulting from the epidural blood volume injected,
      a complication necessitating immediate surgical decompression. We could not find
      a previous report of this in the literature. Here, we review and discuss one such
      case. CASE REPORT: A patient was treated with 2 EDBPs for a presumptive
      cerebrospinal fluid leak 3 weeks after an epidural steroid injection. The second
      EDBP was performed under direct fluoroscopic guidance, yet resulted in spinal
      cord compression with radiologic evidence of an epidural hematoma. The patient
      developed acute cauda equina syndrome and required an emergent decompressive
      laminectomy resulting in partial resolution of neurological symptoms. One year
      after the procedure, the patient has recovered most of her motor function but
      with some persistent numbness below the left knee and a left foot drop.
      CONCLUSIONS: A cauda equina syndrome from an epidural hematoma may occur as a
      rare complication of an EDBP, even with direct fluoroscopic guidance. Early
      diagnosis of symptoms and prompt surgical evacuation of an epidural hematoma is
      essential and may result in the resolution of symptoms. This complication remains
      a rare occurrence and should not deter the performance of an EDBP, when
      indicated.

PMID- 24310045
TI  - Epidural hematomas after removal of percutaneous spinal cord stimulator trial
      leads: two case reports.
AB  - OBJECTIVE: We report 2 cases of spinal epidural hematoma formation after the
      removal of percutaneous spinal cord stimulator trial leads and discuss the
      possible etiologies of these complications. CASE REPORT: Two patients developed
      spinal epidural hematomas shortly after removal of their percutaneous trial leads
      and required multilevel laminectomies for evacuation of the hematoma. Patient 1
      reported taking aspirin the morning that his leads were pulled, whereas patient 2
      had not taken aspirin in the 7 days before commencing his trial. There were 2
      days between identification and evacuation of patient 1's hematoma, and he did
      not fully recover from the injury to his spinal cord. Patient 2 underwent surgery
      immediately with complete resolution of his symptoms. CONCLUSIONS: Currently, the
      neuromodulation community ascribes to the American Society of Regional Anesthesia
      and Pain Medicine guidelines, which state that nonsteroidal anti-inflammatory
      drugs do not significantly increase the risk for epidural hematoma with neuraxial
      anesthesia and, therefore, there is no need to discontinue these drugs before
      epidural or spinal anesthesia. We suggest that these guidelines may not be
      appropriate for neuromodulatory techniques that likely subject the surrounding
      vasculature to more trauma than neuraxial anesthesia. We recommend discontinuing
      nonsteroidal anti-inflammatory drugs, particularly aspirin, before
      neuromodulation procedures. Further investigation will establish a timeframe for
      holding these drugs to optimize patient safety.

PMID- 24310046
TI  - The maximum effective needle-to-nerve distance for ultrasound-guided interscalene
      block: an exploratory study.

PMID- 24310047
TI  - Spinal epidural hematoma after spinal cord stimulator trial lead placement in a
      patient taking aspirin.
AB  - OBJECTIVE: Spinal epidural hematoma is a rare, but potentially devastating,
      consequence of accessing the epidural space for anesthesia or interventional pain
      procedures. There is no consensus to stop aspirin therapy before interventional
      chronic pain procedures. CASE REPORT: A 73-year-old woman with postlaminectomy
      pain syndrome and lumbar radiculopathy underwent percutaneous spinal cord
      stimulator lead placement. She had been taking aspirin 81 mg/d for several years.
      Twenty-four hours later, she developed an epidural hematoma. Prompt recognition
      and surgical management resulted in no long-term neurological sequelae.
      CONCLUSIONS: The only variable that could have led to our patient's epidural
      hematoma is aspirin. This is the first reported case of aspirin leading to an
      epidural hematoma following an interventional chronic pain procedure. Prior to
      interventional pain procedures, one should contemplate cessation of aspirin
      therapy because there are, at present, no consensus guidelines to direct such a
      decision.

PMID- 24310048
TI  - Characteristics of chronic pain patients who take opioids and persistently report
      high pain intensity.
AB  - BACKGROUND AND OBJECTIVES: The use of self-report questionnaires to detect
      characteristics of altered central pain processing, as seen in centralized pain
      disorders such as fibromyalgia, allow for the epidemiological studies of pain
      patients. Here, we assessed the relationship between reporting high levels of
      pain while taking opioids and the presence of characteristics associated with
      centralized pain. METHODS: We evaluated 582 patients taking opioid medications
      using validated measures of clinical pain, neuropathic pain symptoms, mood, and
      functioning. A multivariate linear regression model was used to assess the
      association between levels of pain while taking opioids and presenting with
      characteristics consistent with having centralized pain. RESULTS: We found that
      49% of patients taking opioids continued to report severe pain (>= 7/10). In
      multivariate analysis, factors associated with having higher levels of pain in
      opioid users included higher fibromyalgia survey scores (P = 0.001), more
      neuropathic pain symptoms (P < 0.001), and higher levels of depression (P =
      0.002). Although only 3.2% were given a primary diagnosis of fibromyalgia by
      their physician, 40.8% met American College of Rheumatology survey criteria for
      fibromyalgia. CONCLUSIONS: Our findings suggest that patients with persistently
      high pain scores despite opioid therapy are more likely than those with lower
      levels of pain to present with characteristics associated with having centralized
      pain. This study cannot determine whether these characteristics were present
      before (fibromyalgia-like patient) or after the initiation of opioids (opioid
      induced hyperalgesia). Regardless, patients with a centralized pain phenotype are
      thought to be less responsive to opioids and may merit alternative approaches.

PMID- 24310049
TI  - Increases in the use of prescription opioid analgesics and the lack of
      improvement in disability metrics among users.
AB  - BACKGROUND AND OBJECTIVES: In the United States, use of oral opioid analgesics
      has been associated with increasing rates of addiction, abuse, and diversion.
      However, little is known about the recent national use of non-illicit
      prescription opioid analgesics (those prescribed in a physician-patient
      relationship), the primary source of these drugs for the general US population.
      Our primary objective was to examine trends in the use of prescription opioid
      analgesics in the United States and to identify defining characteristics of
      patient users of prescribed opioids from 2000 to 2010. METHODS: We used the
      nationally representative Medical Expenditure Panel Survey to examine trends in
      prescription oral opioid analgesic use from 2000 to 2010. We used survey design
      methods to make national estimates of adults (18 years and older) who reported
      receiving an opioid analgesic prescription (referred to as opioid users) and used
      logistic regression to examine predictors of opioid analgesic use. Our primary
      outcome measures were national estimates of total users of prescription opioid
      analgesics and total number of prescriptions. Our secondary outcome was that of
      observing changes in the disability and health of the users. RESULTS: The
      estimated total number of opioid analgesic prescriptions in the United States
      increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an
      estimated 7.4% (95% confidence interval, 6.9-7.9) of adult Americans were
      prescription opioid users compared with 11.8% (95% confidence interval, 11.2
      12.4) in 2010. On the basis of estimates adjusted for changes in the general
      population, each year was associated with a 6% increase in the likelihood of
      receiving an opioid prescription from 2000 to 2010. Despite the apparent increase
      in use, there were no demonstrable improvements in the age- or sex-adjusted
      disability and health status measures of opioid users. CONCLUSIONS: The use of
      prescription opioid analgesics among adult Americans has increased in recent
      years, and this increase does not seem to be associated with improvements in
      disability and health status among users. On a public health level, these data
      suggest that there may be an opportunity to reduce the prescribing of opioid
      analgesics without worsening of population health metrics.

PMID- 24310051
TI  - Are patients satisfied after peripheral nerve blockade? Results from an
      International Registry of Regional Anesthesia.
AB  - INTRODUCTION: Peripheral nerve blockade (PNB) is associated with superior
      outcomes compared with opioids; however, little is known regarding patients'
      perceptions of the care they have received. Patient satisfaction is emerging as
      an important indicator of quality of health care, and identifying deficiencies in
      discrete aspects of satisfaction may allow targeted interventions to improve
      quality. In this study, we analyze data relevant to patient satisfaction from the
      International Registry of Regional Anesthesia. The primary objective of this
      analysis was to report the results of a patient-satisfaction questionnaire and to
      determine predictors associated with unwillingness to have PNB repeated in the
      case of future surgery. METHODS: The questionnaire used in this study was derived
      from this registry's results and from previously validated questionnaires and
      addressed 3 domains of importance, namely, provision of information, pain, and
      interaction with the anesthesiologist. The 11-item written, multidimensional
      questionnaire was given to patients within 2 days postoperatively. The primary
      outcome was willingness to have PNB repeated in the event of future similar
      surgery. RESULTS: Data related to 9969 surgical procedures were collected between
      July 1, 2011, and March 31, 2013. The survey response rate was 61.6%. Most
      respondents-94.6% (95% confidence interval, 94.0%-95.1%)--stated that they were
      willing to have a repeat PNB. Ninety percent of respondents were satisfied or
      completely satisfied with the information provided about the nerve block, as well
      as the anesthesiologist-patient interaction. Patients who were dissatisfied with
      either of these domains (ie, information provision or professional interaction)
      were less willing to undergo repeat PNB, as were patients who reported
      significant pain during the nerve block procedure. CONCLUSIONS: A high proportion
      of survey respondents were willing to undergo repeat PNB in case of future
      surgery and were satisfied with their anesthetic care. Targeted interventions to
      improve quality of PNB should be aimed at improving comfort, information
      provision, and physician-patient interaction.

PMID- 24310052
TI  - Cognition and nutrition.
AB  - PURPOSE OF REVIEW: Aging is associated with a decline in cognition. This review
      examines the available data on the effects of nutrition on cognitive impairment.
      It also explores the mechanism(s) by which food may enhance memory. RECENT
      FINDINGS: An increasing body of evidence has supported the role of the
      Mediterranean diet and extra-virgin olive oil in protecting cognition. A number
      of nutritional formulations to improve deteriorating memory are being studied.
      Undernutrition is associated with cognitive decline. Hyperglycemia and
      hypertriglyceridemia cause cognitive impairment. SUMMARY: There are increasing
      data to support the role of nutrition in maintaining cognition.

PMID- 24310050
TI  - The effect of nitrous oxide anesthesia on early postoperative opioid consumption
      and pain.
AB  - BACKGROUND AND OBJECTIVES: Many patients experience moderate to severe
      postoperative pain. Nitrous oxide (N2O) exerts analgesia by inhibition of N
      methyl-D-aspartate receptors. Ketamine, another N-methyl-D-aspartate receptor
      antagonist, reduces postoperative opioid consumption and pain. A similar effect
      of N2O is plausible, yet understudied. The goal of this study was to determine
      the effects of N2O anesthesia on early postsurgical opioid consumption and pain.
      METHODS: This was a retrospective, secondary analysis of the Vitamins In Nitrous
      Oxide trial, where 500 patients undergoing general anesthesia for noncardiac
      surgery received 60% N2O and 125 received no N2O (otherwise, inclusion/exclusion
      criteria were identical). Exclusion criteria for this study were regional
      anesthesia, not extubated after surgery, transfer to intensive care unit, no
      available postanesthesia care unit record, postsurgical sedation, or treated with
      naloxone. Primary outcomes were cumulative opioid consumption measured in
      morphine equivalents and pain scores during the immediate recovery phase.
      RESULTS: Four hundred forty-two patients met inclusion criteria. No difference in
      intraoperative and postoperative opioid consumption was observed between patients
      who received N2O (n = 353) and patients who did not (n = 89). The median
      [interquartile range] postoperative morphine equivalent dose was 6.7 mg [1.7-14.1
      mg] for patients who received N2O and 6.7 mg [2.1-15.4 mg] for patients who did
      not (P = 0.73). The maximum pain score was 6 [4-8] for patients who received N2O
      versus 6 [3-8] for patients who received N2O-free anesthesia (P = 0.52). The
      prevalence of moderate to severe pain was 69% for patients who received N2O and
      68% for patients who did not (P = 0.90). CONCLUSIONS: Nitrous oxide anesthesia
      was not associated with decreased opioid administration, pain, or incidence of
      moderate to severe pain in the early postoperative phase.

PMID- 24310054
TI  - Exercise as a remedy for sarcopenia.
AB  - PURPOSE OF REVIEW: Although prolongation of life is a significant public health
      aim, at the same time the extended life should involve preservation of the
      capacity to live independently. Consequently, the identification of cost
      effectiveness interventions to prevent frailty is one of the most important
      public health challenges. In the present review, we present the available
      evidence regarding the impact of physical exercise on the components of frailty
      syndrome and, in particular, as a remedy for sarcopenia. RECENT FINDINGS:
      Resistance exercise training is more effective in increasing muscle mass and
      strength, whereas endurance exercises training is superior for maintaining and
      improving maximum aerobic power. Based on these evidences, recommendations for
      adult and frail older people should include a balanced program of both endurance
      and strength exercises, performed on a regular schedule (at least 3 days a week).
      SUMMARY: Regular exercise is the only strategy found to consistently prevent
      frailty and improve sarcopenia and physical function in older adults. Physical
      exercises increase aerobic capacity, muscle strength and endurance, by
      ameliorating aerobic conditioning and/or strength. In older patients, exercise
      and physical activity produce at least the same beneficial effects observed in
      younger individuals.

PMID- 24310053
TI  - Dietary protein and muscle in older persons.
AB  - PURPOSE OF REVIEW: The purpose of this study is to highlight recent advances in
      nutrition and protein research that have the potential to improve health outcomes
      and status in ageing adults. RECENT FINDINGS: The beneficial effects of dietary
      protein on muscle health in older adults continue to be refined. Recent research
      has bolstered support for moderately increasing protein consumption beyond the
      current Recommended Dietary Allowance by adopting a meal-based approach in lieu
      of a less specific daily recommendation. Results from muscle protein anabolism,
      appetite regulation and satiety research support the contention that meeting a
      protein threshold (approximately 30 g/meal) represents a promising strategy for
      middle-aged and older adults concerned with maintaining muscle mass while
      controlling body fat. SUMMARY: Optimizing dietary protein intake to improve
      health requires a detailed consideration of topics including muscle protein
      anabolism, appetite control and satiety. Although each area of research continues
      to advance independently, recent collaborative and translational efforts have
      highlighted broad, translational consistencies related to the daily distribution
      and quantity of dietary protein.

PMID- 24310055
TI  - Amino acids and proteins important for all; from stem cells, to the critically
      ill patient and even general bone health.

PMID- 24310056
TI  - Protein diets, body weight loss and weight maintenance.
AB  - PURPOSE OF REVIEW: The review addresses briefly the relevance of protein diets
      for body weight loss and weight maintenance. The addition of recent findings on
      age-dependent protein requirements, specific effects of protein intake and
      protein source, the relevance of the other dietary macronutrients, especially of
      'low-carb', 'protein leverage', the mechanisms of protein-induced satiety, and
      food-reward makes the review up-to-date. RECENT FINDINGS: Different effects of
      protein diets in different age groups result from age-dependent protein
      requirements that are primarily related to effects on body composition. A protein
      intake of 0.8 g/kg/day is sufficient to sustain a negative energy balance in
      adults, irrespective of the protein source. 'Low-carb' diets trace back to the
      protein-induced effects. Evidence that protein intake drives energy intake as
      suggested by the 'Protein leverage hypothesis' is scarce and equivocal. Finally,
      limited protein-induced food reward may affect compliance to a protein diet.
      SUMMARY: An implication of the findings for clinical practice is that a protein
      intake of 0.8-1.2 g/kg/day is sufficient to sustain satiety, energy expenditure,
      and fat-free mass, independent of a dietary 'low-carb' content. Limited protein
      induced food reward may affect compliance to a protein diet.

PMID- 24310057
TI  - Branch chain amino acids: biomarkers of health and disease.
AB  - PURPOSE OF REVIEW: There is burgeoning evidence that branch chain amino acids
      (BCAAs) are biomarkers of metabolic, cardiovascular, renal and cerebrovascular
      disease. The purpose of this review is to summarize the current evidence in this
      area. RECENT FINDINGS: Recent evidence demonstrates that BCAAs are associated
      with insulin resistance, type 2 diabetes, risk of cardiovascular disease, stage I
      and II chronic kidney disease and ischemic stroke. Further, circulating levels of
      BCAAs have the potential to predict populations at risk for cardiometabolic
      disease, type 2 diabetes and mortality from ischemic heart disease. Importantly,
      the relationship of BCAAs to insulin resistance is affected by the intake of fat
      in the diet as well as age. SUMMARY: Current evidence supports the potential use
      of BCAAs as biomarkers of disease. However, questions regarding the mechanisms
      underlying the relationship of BCAAs to disease process and severity need to be
      answered prior to the use of BCAAs as a biomarker in clinical practice.

PMID- 24310059
TI  - Ophthalmologic outcome at 30 months' corrected age of a prospective Swedish
      cohort of children born before 27 weeks of gestation: the extremely preterm
      infants in sweden study.
AB  - IMPORTANCE: Follow-up at 30 months' corrected age reveals eye and visual problems
      in one-third of children born extremely prematurely (<27 weeks' gestation).
      OBJECTIVE: To investigate the ophthalmologic outcome of extremely preterm
      children at 30 months' corrected age. DESIGN, SETTING, AND PARTICIPANTS A
      prospective, population-based follow-up study (Extremely Preterm Infants in
      Sweden Study [EXPRESS]) was conducted in Sweden. The population included
      extremely preterm infants (<27 weeks' gestation) born in Sweden between 2004 and
      2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of
      prematurity (ROP) was performed in the neonatal period. At 30 months' corrected
      age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%).
      MAIN OUTCOMES AND MEASURES: Visual acuity, manifest strabismus, and refractive
      errors were evaluated. RESULTS: Visual impairment was identified in 3.1% of the
      children, and 1.0% were blind. Refractive errors, defined as myopia less than -3
      diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or
      anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had
      manifest strabismus. There were significant associations between visual
      impairment and treated ROP (P = .02), cognitive disability (P < .001), and birth
      weight (P = .02). Multiple regression analyses revealed significant associations
      between strabismus and treated ROP (P < .001), cognitive disability (P < .01),
      and cerebral palsy (P = .02). Refractive errors were significantly correlated
      with severity of ROP (right eye, P < .001; left eye, P < .01). Children who had
      been treated for ROP had the highest frequency (69.0%) of eye and visual
      abnormalities. CONCLUSIONS AND RELEVANCE: One-third of the extremely prematurely
      born children in this study had some kind of eye or visual problems, such as
      visual impairment, strabismus, or major refractive error. Despite being born
      extremely preterm, the present cohort has a similar prevalence of blindness and
      visual impairment as in previous Swedish cohorts of children born less
      prematurely.

PMID- 24310060
TI  - SERS-based competitive immunoassay of troponin I and CK-MB markers for early
      diagnosis of acute myocardial infarction.
AB  - We report a SERS-based competitive immunoassay technique for the early diagnosis
      of acute myocardial infarction (AMI). Simultaneous quantification of the dual
      cardiac markers, CK-MB and troponin I, was achieved by single wavelength
      excitation. 

PMID- 24310061
TI  - Human neural stem cells expressing carboxyl esterase target and inhibit tumor
      growth of lung cancer brain metastases.
AB  - Neural stem cells (NSCs) led to the development of a novel strategy for
      delivering therapeutic genes to brain tumors. Human NSCs expressing rabbit
      carboxyl esterase (F3.CE), which activates CPT-11, significantly inhibit the
      growth of A549 human non-small cell lung adenocarcinoma cells in the presence of
      CPT-11 in vitro and in vivo. F3.CE cells migrated selectively into the brain
      metastases located in the opposite hemisphere. The treatment also significantly
      decreased tumor volume in immune-deficient mice bearing lung cancer when F3.CE
      cells were transplanted into the contralateral hemisphere. The survival of tumor
      bearing animals was significantly prolonged by the treatment with F3.CE and CPT
      11. This strategy could be considered as an effective treatment regimen for lung
      cancer brain metastases. 

PMID- 24310063
TI  - Alarm substances of the stingless bee,Trigona silvestriana.
AB  - 2-Nonanol, 2-heptanol, octyl decanoate, and octyl octanoate were identified from
      the heads ofTrigona silvestriana workers. When presented at the nest, 2-nonanol,
      2-heptanol, and the mixture of the four compounds elicited angular flights,
      landing, and buzzing of guard bees. Octyl octanoate elicited a weaker response.
      No response was given to octyl decanoate, to the ether solvent, or to the control
      volatile, vanillin. 

PMID- 24310062
TI  - DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core
      antigens generates robust cytotoxic and antibody responses in mice and Rhesus
      macaques.
AB  - There are well over a quarter of a billion chronic hepatitis B virus (HBV)
      carriers across the globe. Most carriers are at high risk for development of
      liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is
      therefore imperative to develop new approaches for immunotherapy against this
      infection. Antibodies and cytotoxic T cells to different HBV antigens are
      believed to be important for reducing viral load and clearing HBV-infected cells
      from the liver. Some of the major challenges facing current vaccine candidates
      have been their inability to induce both humoral and cellular immunity to
      multiple antigenic targets and the induction of potent immune responses against
      the major genotypes of HBV. In this study, highly optimized synthetic DNA
      plasmids against the HBV consensus core (HBc) and surface (HBs) antigens
      genotypes A and C were developed and evaluated for their immune potential. These
      plasmids, which encode the most prevalent genotypes of the virus, were observed
      to individually induce binding antibodies to HBs antigens and drove robust cell
      mediated immunity in animal models. Similar responses to both HBc and HBs
      antigens were observed when mice and non-human primates were inoculated with the
      HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited
      by the immunized mice, the vaccine-induced responses were broadly distributed
      across multiple antigenic epitopes. These elements are believed to be important
      to develop an effective therapeutic vaccine. These data support further
      evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines. 

PMID- 24310064
TI  - Lasioderma chemistry sex pheromone of cigarette beetle (Lasioderma serricorne
      F.).
AB  - A chemical study of the sex pheromone of the cigarette beetle was carried out.
      Seven components were isolated from active fractions of column chromatography of
      the female extract, and their structures were elucidated by spectroscopic
      evidence and confirmed by synthesis to be (4S,6S,7S)-4,6-di-methyl-7-hydroxynonan
      3-one (serricornin) (I), 2,6-diethyl-3,5-dimethyl-3,4-dihydro-2H-pyran
      (anhydroserricornin) (II), 4,6-dimethylnonan-3,7-dione (III), 4,6-dimethylnonan
      3,7-diol (IV), 4,6-dimethyl-7-hydroxy-4-nonen-3-one (V), (2S,3R)-2,3-dihydro-3,5
      dimethyl-2-ethyl-6-(l-methyl-2-oxobutyl)-4H-pyran-4-one (serricorone) (VI) and
      (2S,3R)-2,3-dihydro-3,5-dimethyl-2-ethyl-6-(1-methyl-2-hydroxybutyl)-4H-pyran-4
      one (serricorole) (VII).These structural features suggested that the occurrence
      of these components might be related to the polyketide biosynthesis. The
      behavioral bioassay and BAG experiments revealed the biological role of each
      component in the copulatory behavior of this insect. 

PMID- 24310065
TI  - Influence of cage design on precision of tube-trap bioassay for attractants of
      the onion fly,Delia antiqua.
AB  - Responses of onion flies,Delia antiqua, to known attractants were measured in the
      laboratory with a novel tube-trap bioassay. The relative numbers of flies caught
      in tube traps baited with enzymatic yeast hydrolysate, brewer's yeast, andn
      dipropyl disulfide were similar to those obtained previously with cone traps in
      the field. Changing the shape of the bioassay cage from a cuboid to a cylinder
      decreased the experimental error obtained from analysis of variance, as did
      rotating the floor of the circular cage. This bioassay should be useful in
      evaluating attractants for other insects that orient along the substrate. 

PMID- 24310066
TI  - Isolation ofC-glycosylflavones as probing stimulant of planthoppers in rice
      plant.
AB  - Three species of planthopper,Nilaparvata lugens,Sogatella furcifera,
      andLaodelphax striatellus, showed characteristic behavior of stylet probing in
      parenchymal tissues of plants. Feeding experiments of planthoppers on aqueous
      sucrose solution containing the extract of rice plants or barnyard grass revealed
      the presence of the stimulant for the probing behavior in the plant tissues.
      EightC-glycosylflavones which stimulated stylet probing were isolated from rice
      plants. Four of them were identified to be schaftoside, neoschaftoside,
      carlinoside, and neocarlinoside, the last one being a new compound isolated from
      the plant. The isolatedC-glycosylflavones showed the same level of the activity
      for the probing ofN. lugens as the rice plant extract only when all of them were
      combined. 

PMID- 24310067
TI  - Role of host-produced stimuli and learning in host selection behavior ofCotesia
      (=Apanteles) marginiventris (Cresson).
AB  - The study was conducted to determine how various factors, including learning,
      influence the host-selection behavior of the larval parasitoid Cotesia
      (=Apanteles)marginiventris (Cresson). Frass, silk, and feeding damage
      fromSpodoptera frugiperda (J.E. Smith) larvae elicited visits and antennal
      examinations by females of the parasitoid. Learning played a role in the
      effective response to these stimuli in that previous contact experience with
      hosts and/or chewed leaves, exuviae, frass, or hemolymph significantly enhanced
      the response of the parasitoid. Previous contact with host plants alone did not
      improve the responses. Experienced parasitoids were more active and spent less
      time at rest than inexperienced parasitoids. Previous experience was also found
      to be of significant importance in the ability of the parasitoid to discriminate
      between parasitized and unparasitized host larvae. 

PMID- 24310068
TI  - Defensive secretions of New Zealand tenebrionids V. Presence of methyl ketones
      inUloma tenebrionoides (Coleoptera: Tenebrionidae).
AB  - The defensive secretion ofUloma tenebrionoides (White, 1846) contains
      benzoquinone, 2-methylbenzoquinone (toluquinone), and 2-ethylben-zoquinone as in
      other tenebrionids, together with 2-methoxyphenol, pentadecene, heptadecene, 2
      pentanone, 2-pentadecanone, 2-heptadecanone, heptadec-10-en-2-one and (Z)-nonadec
      10-en-2-one. The latter four methyl ketones have not previously been identified
      in tenebrionid beetles, and the unsaturated ketones are novel arthropod
      chemicals. 

PMID- 24310069
TI  - Evaluation of plant constituents associated with pecan phylloxera gall formation.
AB  - The weights of pecanCarya illinoensis Koch galls caused by several species
      ofPhylloxera (Homoptera: Phylloxeridae) were negatively correlated with leaf and
      nut weights and nut production. Several allelochemicals (isoquercitrin, juglone,
      and 2 proanthocyanidins) were isolated from galls, and their antibiotic
      potentials were estimated, based on their toxicity to the bacteriaPseudomones
      maltophilia (Hugh et Ryschenkow). Pecan proanthocyanidins (condensed tannins)
      were characterized for the first time, and their stereochemistry was elucidated.
      The protein and total sugar contents of total leaves and leaf surface washings
      were determined. The leaf surface sugar content was very low, suggesting that the
      puncturing strategy of this insect may be for the purpose of finding sugars. The
      plant growth hormones gibberellic acid, zeatin, zeatin riboside, kinetin, indole
      acetic acid, and abscisic acid were found in pecan leaves, stems, and their
      galls. Gibberellic and abscisic acids were present in highest concentrations in
      all tissues, but lower in galled tissues, suggesting that increased biosynthesis
      by pecan plant growth regulators did not occur in response to insect attack. 

PMID- 24310070
TI  - Effects of surfactants, pH, and certain cations on precipitation of proteins by
      tannins.
AB  - Tannic acid and pin oak tannins precipitate large amounts of the abundant leaf
      protein, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPC), over a wide pH
      range (6.15-9.30) in the presence of sodium, potassium, magnesium, and calcium
      ions at concentrations comparable to those reported in the gut fluids of
      lepidopteran herbivores. The presence of lysolecithin, a surfactant known to be
      present in the gut fluids of some insects, significantly reduces the amount of
      RuBPC precipitated under these conditions. We conclude that high detergency is
      far more effective than high alkalinity in countering the potential protein
      precipitating properties of tannins. We further conclude that tannins do not
      deserve the status they were once accorded as general, all-purpose, dose
      dependent, antidigestive defensive chemicals. We also describe the application of
      the Schaffner-Weissman protein assay for studying the protein-precipitating
      capacity of plant extracts. This method is far superior to the one we have used
      in our earlier studies. 

PMID- 24310071
TI  - Olfactory behavior of red flour beetleTribolium castaneum (Herbst) (Coleoptera,
      Tenebrionidae) towards natural fatty acid esters.
AB  - The olfactory responses of red flour beetles,Tribolium castaneum (Herbst), to
      methyl and ethyl ester of C14-C18 fatty acid prepared from tallow were studied.
      Methyl octadecanoate and ethyl octadecanoate discouraged aggregation of beetle
      adults. Ethyl 9.12-octadecadienoate acted as a repellent. Methyl pentadecanoate
      and ethyl tetradecanoate induced copulation at the level of 5 * 10(2) and 2 *
      10(3) MUg, respectively. The maximum response was observed at the level of 5 *
      10(2) MUg of the same compounds, and these compounds appear to stimulate males
      only. 

PMID- 24310072
TI  - Structure-activity relationships among maytansinoids in their effect on the
      European corn borer,Ostrinia nubilalis (Hubner).
AB  - Five maytansinoids fromMaytenus (Celastraceae) andPutterlickia (Rhamnaceae)
      species were tested for biological activity against the European corn
      borerOstrinia nubilalis. Maytanbutine, maytansine, and maytanvaline, all of which
      contain an amino acid residue at C-3, were active and comparable in their effect
      on larvae to trewiasine, a known active, amino acid-containing maytansinoid
      fromTrewia nudiflora. Maytanacine, which has an acetate group at C-3, was not as
      active as maytansine, maytanvaline, maytanbutine, or trewiasine, but
      significantly retarded the development of the larvae. Normaysine, which has no
      oxygen substituent at C-3, had no significant effect on mortality and only
      moderate effect on development of the larvae. The presence of the amino acid
      moiety at C-3 appears to be an important factor for the biological activity of
      maytansinoids. 

PMID- 24310073
TI  - Effect of hypoxanthine-3(N)-oxide and hypoxanthine-1(N)-oxide on central nervous
      excitation of the black tetraGymnocorymbus ternetzi (Characidae, Ostariophysi,
      Pisces) indicated by dorsal light response.
AB  - The change of state in the central nervous system ofGymnocorymbus ternetzi after
      detection of hypoxanthine-l(N)-oxide, hypoxanthine-3(N)-oxide, and of the alarm
      substance from conspecifics was measured quantitatively by means of the fishes'
      equilibrium behavior. The fish swam freely in a tiny cage, illuminated
      horizontally from one side. The change of the angle of inclination of the
      dorsoventral axis of the fish was registered by means of a videorecorder. The
      recordings were later measured on the monitor in single frames at 0.2-sec
      intervals where the equilibrium position of the fish could be accurately
      determined +/- 1  degrees . Various substances were presented to the fish, and
      their effects upon equilibrium position were recorded. An enhanced optical
      alertness shown by an increase in the fishes' inclination was generally produced
      with alarm substance. Without any additional stimulation, the factorU,
      representing quantitatively the degree of the change of central state, varied
      slightly within the experimental period of 1 min; however, this factor never
      exceededU= 1.0 +/- 0.15 in control fish. The increase ofU usually exceeded
      considerably the value 1.15 when skin extract from conspecifics or 7-8 MUg of
      hypoxanthine-3(N)-oxide were given. However, when hypoxanthine-l (N)-oxide was
      presented,U generally did not exceed 1.15. The difference between hypoxanthine
      3(N)-oxide and hypoxanthine-l(N)-oxide was highly significant. This result is in
      accordance with the findings on fish schools ofDanio malabaricus, where
      hypoxanthine-3(N)-oxide elicited the fright reaction, but hypoxanthine-1(N)-oxide
      was ineffective. The results support the hypothesis that the alarm substance from
      the skin ofPhoxinus phoxinus is identical with hypoxanthine-3(N)-oxide. The
      results with alarm substance or hypoxanthine-3(N)-oxide did not show any
      adaptation. This was also true in fish that were stimulated repeatedly at
      intervals of a couple of minutes only. InGymnocorymbus, which has compensated for
      removal of the otolith of one utriculus, conspecific skin extract triggers the
      typical postoperative phenomenon, i.e., rotation around the fishes' long axis
      towards the operated side. Whereas such a decompensation could be elicited by
      hypoxanthine-3(N)-oxide as well, hypoxanthine-l(N)-oxide had no effect. This
      finding is interpreted as an effect of the alarm substance and of hypoxanthine
      3(N)-oxide on the centers of equilibrium. 

PMID- 24310074
TI  - Constituents of mandibular and Dufour's glands of an australianPolyrhachis weaver
      ant.
AB  - Worker ants ofPolyrhachis (Cyrtomyrma) ?doddi collectively discharge the
      secretions of their large mandibular glands when their nest is disturbed. The
      major glandular compounds of workers are 6-methylhept-5-en-2-one and
      phenylacetaldehyde oxime. Other components identified are mellein, 6-methylhept-5
      en-2-one oxime, phenylacetonitrile, phenyiacetaldehyde, benzaldehyde, and several
      alkanes and alkenes. The mandibular gland secretions of queens differ from those
      of workers only quantitatively. Large queens have considerably more of most
      components, the small queens have much less of volatile components. There is a
      pronounced sexual difference: the major components of the male's secretions are
      octanoic acid and mellein, with geranic acid, 8-heptadecene, 2-methylbutanoic
      acid, and 9-nonadecene present in lesser amounts. Workers ofP. ?doddi also have
      unusually large Dufour's glands containing a large array of hydrocarbons, of
      which tridecane is the major component, but alpha-farnesene, pentadecane, and
      heptadecene are also present in large quantities. 

PMID- 24310075
TI  - Ammonia utilization by the bruchid beetle,Caryedes brasiliensis [Bruchidae].
AB  - The seed predator,Caryedes brasiliensis [Bruchidae] generates appreciable ammonia
      in its dietary use and detoxification ofL-canavanine and its catabolic product,L
      canaline.L-Canavanine is a toxic allelochemical ofDioclea megacarpa seeds, the
      food of the developing larvae. Bruchid beetle larvae rely upon glutamic acid
      dehydrogenase and glutamine synthetase to use ammonia for glutamic acid synthesis
      from 2-oxoglutaric acid and conversion of the former to glutamine. These
      reactions provide the larvae with a means for metabolically eliminating ammonia.
      Proline serves as a carbon skeleton source for glutamic acid formation. 

PMID- 24310076
TI  - Professionals, amateurs, and the cure of souls.

PMID- 24310077
TI  - Toward a theology of healing.
AB  - A sense of magic has always permeated our theology of healing. Consider the
      following theses: 1. By the very nature of material creation, however
      mysteriously it was initiated and is sustained, the power of God to influence
      material creation is restricted to the immanent (from within) and indirect; 2.
      God does not arbitrarily, in the case of two persons who have "identical"
      illnesses, decide the recovery of one and the death of the other. Rather, his
      love bears equally on all. This study will defend these theses and show that they
      are foundational and integral, to a theology of primarily physical healing. 

PMID- 24310078
TI  - The physician as moral entrepreneur.
AB  - This paper argues that the work of the contemporary physician is at least in part
      the work of a moral entrepreneur. The effects of religious affiliation and
      religiosity on the decision making of a modern doctor are examined in an analysis
      of the responses of 231 physicians to a mailed questionnaire. Decision-making
      issues were considered to be those with social/moral implications. Religious
      physicians tend to favor clergy involvement in social and procreative issues.
      Roman Catholic physicians oppose the involvement of the medical profession in
      birth control issues. 

PMID- 24310079
TI  - Self-help groups for the bereaved: Theory, theology, and practice.
AB  - Self-help groups for the bereaved are a relatively unexplored area of wholistic
      ministry. The article grows out of the author's experience as an advisor to a
      local chapter of The Compassionate Friends, a group of parents whose children
      have died. The article explores the self-help concept, describes the experience
      of losing a child and the way the self-help process functions in that dynamic,
      and enumerates some roles the author has been able to fill as an aid to a local
      chapter. Within that framework, the article shows the affinities between self
      help and ministry. 

PMID- 24310080
TI  - Working with the separated and divorced.
AB  - The article describes the structure, the topics, and some of the activities of a
      workshop for people who are separated and/or divorced. 

PMID- 24310081
TI  - Reintegrative counseling: Reversing secular dissociation.
AB  - The argument is made that counseling emphasizes the unique elements in each
      individual and thus differs from medicine, which seeks generalizations. By
      analogy to secularization of classic Greek religious drama, which did not result
      from any known social imperative, it is suggested that the fragmentation of
      modern man may have occurred unintentionally and is therefore a reversible
      process. The role of the counselor is to catalyze the reintegration of the
      intellectual, emotional, and spiritual components through a close subjective
      identification with the client. 

PMID- 24310082
TI  - Religion, mental health, and clinical issues.
AB  - This article reviews a number of studies investigating the relationship between
      religion and the variables of mental health and social behavior. Characteristics
      of religious health and pathology are examined, and a framework for clinical
      assessment and treatment of religious pathology is described. Tentative
      conclusions concerning the subject matter are drawn and limitations of the number
      and type of studies are outlined. 

PMID- 24310083
TI  - Burnout: A critical issue for the 1980s.
AB  - The article surveys some of the recent literature on burnout and identifies the
      burnout syndrome as a critical issue for our times. What is burnout? Are there
      identifiable causes and characteristics of the phenomenon? Why does it seem to
      affect committed people in the helping professions? Five critical aspects of the
      problem are explored, namely, the difficulty of diagnosis, the relation between
      the existential situation and the person, the sheer weight of change, the
      increasing demands of ministry, and the narrow perception of leisure. Some
      approaches to the problem are presented. These are prevention, self-assessment, a
      new approach to change, re-evaluation of ministry, and creative leisure. The
      creative development of leisure is seen as the most inclusive and effective
      approach to this malady of dedicated people. In fact, leisure attitudes are
      essential for the growth of integrated, balanced, fully human, fully religious
      persons. The author suggests that the development of a spirituality of leisure
      may be the qualitative step needed to eradicate burnout and restore health and
      wholeness to committed persons. 

PMID- 24310084
TI  - Myosin 1g regulates cytoskeleton plasticity, cell migration, exocytosis, and
      endocytosis in B lymphocytes.
AB  - Myosin 1g (Myo1g) is a hematopoietic-specific myosin expressed mainly by
      lymphocytes. Here, we report the localization of Myo1g in B-cell membrane
      compartments such as lipid rafts, microvilli, and membrane extensions formed
      during spreading. By using Myo1g-deficient mouse B cells, we detected
      abnormalities in the adhesion ability and chemokine-induced directed migration of
      these lymphocytes. We also assessed a role for Myo1g in phagocytosis and
      exocytosis processes, as these were also irregular in Myo1g-deficient B cells.
      Taken together, our results show that Myo1g acts as a main regulator of different
      membrane/cytoskeleton-dependent processes in B lymphocytes. 

PMID- 24310085
TI  - Regulatory T cells: Going over to the dark side.

PMID- 24310086
TI  - Neonatal immunity: Hush-a by baby.

PMID- 24310087
TI  - Immune evasion: Staphylococcus slips through the net.

PMID- 24310088
TI  - [Neuropsychological profiles of adolescents with bipolar disorder and adolescents
      with a high risk of bipolar disorder].
AB  - PURPOSE: In recent years evidence of an association between bipolar disorder
      (BD), and specific neuropsychological impairment and familial transmission of BD
      has been mounting. The aim of this study was to identify the clinical and
      neuropsychological features of BD in adolescents, to assess the clinical and
      neuropsychological parameters in adolescents with a high risk of familial
      transmission of BD, and to identify probable early markers of the disorder.
      MATERIALS AND METHODS: The study included 25 patients aged 12-18 years that were
      diagnosed as BD (case group), 25 adolescents without a mood disorder that had a
      parent and/or sibling diagnosed as BD, (risk group), and 25 typically developing
      adolescents (control group). To determine neuropsychological profiles the
      participants were administered the Wisconsin Card Sorting Test (WCST), Stroop
      Color Word Test (SCWT), and Continuous Performance Test (CPT), and to evaluate
      clinical and behavioral profiles the Children's Depression Inventory (CDI),
      Parent-Young Mania Rating Scale (P-YMRS), Youth Self-Report (YSR), and Conners'
      Parent Rating Scale (CPRS-48) were administered. RESULTS: The case group
      performed significantly lower on the WCST, SCWT, and CPT in terms of executive
      and attention functions, whereas there wasn't a difference between the risk group
      and control group. In addition, significantly more of the adolescents in the case
      and risk groups had clinical and behavioral problems than those in the control
      group. CONCLUSION: The findings show that behavioral and clinical problems were
      more common in the risk group than in the control group, and that the frequency
      of attention and executive function impairment was similar in both of those
      groups. The findings suggest that BD itself may be associated with attention and
      executive function impairments, whereas a familial risk of BD may be associated
      with some behavioral problems. Follow-up and neuroimaging studies conducted with
      a larger number of participants, and neuropsychological test profiles may provide
      more detailed information about the neuropsychological profiles of individuals
      with a genetic risk for BD and may provide descriptive data about where and how
      the biological and psychometric deterioration initiate.

PMID- 24310089
TI  - [Internalized stigmatization in bipolar patients: relationship with clinical
      properties, quality of life and treatment compliance].
AB  - OBJECTIVE: This study aimed to investigate the impact of the internalized
      stigmatization on bipolar disorder (BD) patients. MATERIALS AND METHODS: The
      study included 100 BD patients that provided written informed consent to
      participate. Diagnosis of the BD patients that were in remission and receiving
      outpatient treatment was performed using the Structured Clinical Interview for
      DSM-IV Axis I Disorders (SCID-I) and patient data were recorded using SKIP-TURK.
      In addition, the patients were administered the Internalized Stigma of Mental
      Illness Scale (ISMI), Mood Stabilizer Compliance Questionnaire (MSQC), and World
      Health Organization Quality of Life Assessment, abbreviated form (WHOQOL-BREF).
      RESULTS: Internalized stigmatization was observed in 46% of the BD patients;
      these patients had higher functionality scores, shorter regression periods, and
      more depressive episodes than those without internalized stigmatization. Although
      internalized stigmatization occurred more frequently in seasonal and rapid
      cycling patients, both attributes were prodrome of internalized stigmatization.
      Internalized stigmatization was observed more frequently in patients with low
      socioeconomic status, low level of education, rural residence, lack of work, and
      more children. There was a strong correlation between ISMI score, and WHOQOL-BREF
      and MSQC scores. CONCLUSION: The clinical features of the BD and internalized
      stigmatization were observed to affect each other. Furthermore, stigmatization
      affected treatment compliance and quality of life.

PMID- 24310090
TI  - [The mediator role of cognitive features in the relationship between adult
      attachment patterns and psychopathology symptoms: cognitive flexibility].
AB  - OBJECTIVE: The principle aim of the study is to investigate the mediator role of
      cognitive flexibility in the known relationship between adult attachment patterns
      and psychopathology symptoms, including depression, Obsessive Compulsive Disorder
      (OCD), and social anxiety. Additionally, this study aims to generate integrative
      data regarding the relationship between early life experiences and
      psychopathology using a cognitive framework. METHOD: There were 992 participants
      (661 women, 331 men) from 14 different colleges across 9 different provinces and.
      participants were evaluated using the Cognitive Flexibility Inventory, the
      Experiences in Close Relationship Scale-II, Beck Depression Inventory, the
      Maudsley Obsessive Compulsive Inventory and the Liebowitz Social Anxiety Scale.
      Structural Equation Modeling and mediator analysis were applied to the data.
      RESULTS: The results showed that there are some partial and full mediator roles
      of the cognitive flexibility-control in the relationship between attachment
      anxiety and depression, OCD and social anxiety for both women and men.Cognitive
      flexibility- control does not mediate the relationship between avoidant
      attachment and psychopathology symptoms for men, but cognitive flexibility
      control has a partial mediator role in the relationship between avoidant
      attachment and both depression and social anxiety for women. CONCLUSION: The
      present study demonstrates that cognitive flexibility- control is an important
      variable in the relationship between attachment patterns and psychopathology
      symptoms in both women and men.

PMID- 24310091
TI  - [Comparison of the level of depression and anxiety in inactive hepatitis B
      carriers and chronic hepatitis B patients].
AB  - OBJECTIVE: The aim of this study was to evaluate the relative contribution of
      chronic illness and the physical effects such illness on the mental status of
      chronic hepatitis B patients by comparing them to inactive hepatitis B carriers,
      based on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating
      Scale (HARS) scores. MATERIALS AND METHODS: The study included 444 participants:
      249 HBsAg-positive inactive carriers (IC group) and 195 chronic hepatitis B
      patients (CH group) that were undergoing follow-up at Adiyaman University
      Research and Education Hospital, Department of Infectious Diseases Department.
      HBV carrier status and chronic hepatitis B were diagnosed based on European
      Association for the Study of Liver (EASL) guidelines. The HDRS and HARS were
      administered to all the participants via psychiatric interview. RESULTS: The
      overall mean HDRS score was 6.2 +/- 8 and the overall mean HARS score was 6.0 +/-
      7.1. Mean HDRS score in the IC group was 7.5 +/- 5.8, versus 8.8 +/- 6.6 in the
      CH group; the difference was significant (P = 0.037). Mean HARS score were
      similar in both groups (P > 0.05). There wasn't a difference in anxiety or
      depression scores based on participants'gender or age (P > 0.05). Additionally,
      there wasn't a correlation between duration of illness, and family history of
      hepatitis or cirrhosis, or anxiety or depression scores (P > 0.05). Anxiety
      scores were higher among the participants with comorbidity, in both CHB and IC
      groups (P= 0.005 and P = 0.001, respectively). Depression scores were higher
      among the IC group participants with comorbidity (P= 0.003). that can occur
      during the treatment and follow-up of chronic hepatitis patients. The presence of
      comorbidity in chronic hepatitis patients increases the risk of psychiatric
      complications. CONCLUSION: Psychiatric comorbidity, particularly anxiety and
      depression, are important problems.

PMID- 24310092
TI  - [The attitudes nurses working at psychiatric hospitals in Turkey have towards
      forensic psychiatric patients and the associated factors].
AB  - OBJECTIVE: To determine the attitudes nurses working at psychiatric hospitals in
      Turkey have towards forensic psychiatric patients and the associated factors.
      MATERIALS AND METHODS: This cross-sectional study included 620 nurses working at
      8 psychiatric hospitals in Turkey that completed >=80% of the Nurses' Attitudes
      Towards Forensic Psychiatric Patients Scale (NAFPPS). Data were evaluated based
      on number-percentage distribution, and the relationship between variables was
      examined via t-test, variance analysis, and correlation analysis. RESULTS: Mean
      age of the nurses was 34.37 +/- 7.48 years and 79.4% were female. Mean NAFPPS
      total and subscale scores were as follows: Xtotal = 69.07 +/- 12.46 (max: 125);
      Xfeelingthreatened = 15.98 +/- 3.61 (max: 30); Xtrust = 20.49 +/- 5.24 (max: 20);
      Xsocialdistance = 10.45 +/- 3.33 (max: 20); Xwillingnesstoprovidecare = 22.31 +/-
      4.25 (max: 40). Gender, place of employment, method of obtaining current
      position, employment status, level of satisfaction working as a psychiatric
      nurse, history of providing treatment to forensic psychiatric patients, having
      knowledge of Turkish laws regarding the treatment of forensic psychiatric
      patients, and thinking that nurses should treat forensic psychiatric patients
      were correlated with the nurses' attitudes towards forensic psychiatric patients,
      whereas age, marital status, place of longest residence, level of education,
      duration of working in the profession, and duration at current hospital were not.
      CONCLUSION: Despite the fact that the nurses working at 8 psychiatric hospitals
      in Turkey considered forensic psychiatric patients threatening, didn't trust
      them, and had a tendency to be socially distant with them, they had a moderate
      level of willingness to provide them proper care.

PMID- 24310093
TI  - [Developing an attitude scale towards attempted suicide cases for evaluating
      emergency medical teams (ASETSA)].
AB  - OBJECTIVE: Suicide attempt is one of the most important risk factors for
      completed suicide, and generally, the first intervention is performed in the
      emergency department. The attitudes of health professionals towards suicide
      attempt cases affect their treatment and medical care. There is no related
      attitude assessment scale for health professionals in Turkey. The aim of this
      study was to develop a scale for assessing the attitudes of emergency medical
      teams towards cases of attempted suicide. METHODS: In this methodological,
      epidemiological study, a pool of 140 items was compiled using a previously
      developed similar scale available in the literature, as well as, testimonies of
      health professionals. Two hundred and fifty-one doctors, nurses and emergency
      medical technicians from 14 local hospitals in Sanliurfa were included in this
      study. Surface validity was determined using the Lawshe content validity index
      and ratio. Factor analysis (principal components) was used to evaluate structural
      validity and internal consistency (Cronbach's alpha), and test-retest reliability
      was analyzed. RESULTS: The mean age of the study cohort was 27.9 +/- 5.15 years,
      and 50% of the participants were female. A 28-entry attitude scale, which
      explained 58.5% of the total variance, was developed, including subscales for
      prevention and protection, individual help, institutional help, triggers and
      psychopathology, casual attributions, and medical help. The Cronbach's alpha
      parameter of the scale was 0.84. In test-retest analysis; there is no significant
      difference between point averages of the first and last application of the scale.
      CONCLUSION: The psychometric features of the developed scale were determined to
      be acceptable.

PMID- 24310094
TI  - [Cognitive functions in patients with obsessive compulsive disorder].
AB  - AIM: This literature review aimed to examine the relationship between cognitive
      impairment and obsessive-compulsive disorder (OCD). Studies based on
      neuropsychological testing were prioritized, but those dealing with clinical
      features, therapy, comorbidity, neuroimaging, and the families of OCD patients
      were also considered. MATERIALS AND METHODS: The literature on cognitive
      impairment in OCD was reviewed and then the studies evaluating the relationship
      with these above mentioned findings were discussed. RESULTS: The clinically most
      important cognitive impairment in OCD is executive dysfunction, followed by
      impaired memory. Cognitive impairment has also been observed in the healthy
      relatives of OCD patients. Findings regarding the effects of comorbidity on
      cognitive function in OCD patients are inconsistent. Brain imaging studies
      suggest that frontostriatothalamic dysfunction might occur in OCD. CONCLUSION:
      Executive dysfunction in OCD patients is well documented; however, the precise
      nature of the relationship between the severity of cognitive dysfunction and the
      clinical features of OCD are not well understood. Longitudinal family studies
      that employ both neuropsychological testing and brain imaging are needed to more
      clearly elucidate the relationship between cognitive dysfunction and OCD.

PMID- 24310095
TI  - [A case of Munchausen Syndrome by proxy in the context of folie a famille].
AB  - The occurrence of similar psychotic symptoms in two or more people is called
      shared paranoid disorder. In this disease, the person who exhibits psychotic
      symptoms first is the "primary patient". The symptoms are contracted by the other
      people through persuasion. This disorder is seen among people who share the same
      house or are emotionally bound. In some cases, shared paranoid disorder may
      include other diagnoses, such as Munchausen Syndrome. This report discusses the
      case of a six-year-old, sexually abused boy who, when admitted to the hospital at
      the age of 10, claimed to have been repeatedly sexually harassed by several
      different people. His family's frequent changes in hospitals, negative
      perceptions of and accusations against medical staff, and improper methods of
      responding to harassment led clinicians to a diagnosis of Munchausen by proxy
      syndrome. In addition, both parents believed the abuse story, suggesting a
      potential diagnosis of shared psychotic disorder. In the literature, Munchausen
      by proxy has rarely been reported with symptoms of sexual abuse. The psychotic
      symptoms were shared by the family, complicating the case. This report emphasizes
      that psychodynamic evaluations of Munchausen by proxy and shared psychotic
      disorder may be helpful in understanding underlying factors. 

PMID- 24310096
TI  - [Antiphospolipid syndrome related chorea gravidarum case with psychotic symptoms
      misdiagnosed as conversion disorder: case report].
AB  - Chorea gravidarum (CG) is a rare movement disorder characterized by rapid,
      irregular randomly distributed involuntary movements during pregnancy. Similar to
      Sydenham chorea, psychiatric symptoms may be observed in cases of CG. CG may be
      idiopathic or secondary to an underlying cause. One of the most common causes of
      CG is antiphospholipid syndrome. Herein we present a case of recurrent CG that
      was considered to be due to antiphospholipid syndrome. The patient had a history
      of 3 pregnancy losses and her fourth pregnancy was treated appropriately,
      resulting in the birth of healthy full-term baby. During the patient's first
      pregnancy CG was accompanied by psychotic symptoms and was misdiagnosed as
      conversion disorder. 

PMID- 24310097
TI  - [Mental Health and Media].

PMID- 24310098
TI  - Protein corona on magnetite nanoparticles and internalization of nanoparticle
      protein complexes into healthy and cancer cells.
AB  - Superparamagnetic magnetite nanoparticles (MNPs) of different surface properties
      are incubated in complicated living fluid, including fetal bovine serum solution,
      cell complete culture medium and cell culture system with/without serum, to
      investigate the alteration of protein corona and its impact on cell
      internalization. The MNPs prepared by co-precipitation method are functionalized
      with L-Lysine (Lys), Glucosamic acid (GA) to obtain amine, carboxyl and hydroxyl
      groups, separately. All the particles adsorb serum proteins to form MNPs-protein
      complexes with the surface charge changing into negative. 1D SDS/PAGE gel images
      analysis indicates that the composition and content of hard protein corona on the
      surface of NPs are related to their functional groups and agglomeration, and the
      total amount of protein in the medium. In cell culture system, particles not only
      adsorb serum proteins, but also associate with cytosolic proteins arising from
      HepG2 and L02 cells. GA modified MNPs (MNPs-GA) exhibit bovine serum albumin anti
      adsorption capability because of the terminal hydroxyl and carboxyl groups. MNPs
      GA also shows the highest cellular uptake and label efficiency compared with
      uncoated MNPs and Lys modified MNPs, due to larger aggregates formation and
      specific protein corona composition, rather than commonly approved electrostatic
      interaction between particles and cells. For the first time, our results provide
      visualized reports on previously neglected, but indispensable protein corona of
      the MNPs after interaction with both healthy and cancer cells, suggesting that
      cytosolic protein corona from cells and aggregation of particles are important
      factors needed to be account for on studying the nano-bio interface.

PMID- 24310099
TI  - Quantitative and pattern recognition analyses of magnoflorine, spinosin, 6'''
      feruloyl spinosin and jujuboside A by HPLC in Zizyphi Semen.
AB  - Two rapid and simple HPLC methods with UV detector to determine three main
      compounds (magnoflorine, spinosin and 6'''-feruloyl spinosin) and evaporative
      light scattering detector (ELSD) to determine jujuboside A were developed for the
      chemical analyses of Zizyphi Semen. Magnoflorine, spinosin, and 6'''-feruloyl
      spinosin were separated with an YMC J'sphere ODS-H80 column (250 mm * 4.6 mm, 4
      MUm) by the gradient elution followed by the isocratic elution using methanol
      with 0.1 % formic acid and water with 0.1 % formic acid as the mobile phase. The
      flow rate was 1.0 mL/min. Jujuboside A was separated by HPLC-ELSD with
      YoungJinBioChrom Aegispak C18-L column (250 mm * 4.6 mm, 5 MUm) column in a
      gradient elution using methanol with 0.1 % formic acid (A) and water with 0.1 %
      formic acid as the mobile phase. These two methods were fully validated with
      respect to linearity, precision, accuracy, stability, and robustness. These HPLC
      methods were applied successfully to quantify four compounds in a Zizyphi Semen
      extract. The HPLC analytical methods were validated for pattern recognition
      analysis by repeated analysis of 91 seed samples corresponding to 48 Zizyphus
      jujuba var. spinosa (J01-J48) and 43 Zizyphus mauritiana (M01-M43). The results
      indicate that these methods are suitable for a quality evaluation of Zizyphi
      Semen.

PMID- 24310100
TI  - Application of magnetic nanoparticle for controlled tissue assembly and tissue
      engineering.
AB  - Magnetic nanoparticles have been subjected to extensive studies in the past few
      decades owing to their promising potentials in biomedical applications. The
      versatile intrinsic properties of magnetic nanoparticles enable their use in many
      biomedical applications. Recently, magnetic nanoparticles were utilized to
      control the cell's function. In addition, intracellular delivery of magnetic
      nanoparticles allowed cell's positioning by appropriate use of magnetic field and
      created cellular cluster. Furthermore, magnetic nanoparticles have been utilized
      to assemble more complex tissue structures than those that are achieved by
      conventional scaffold-based tissue engineering strategies. This review addresses
      recent work in the use magnetic nanoparticle for controlled tissue assembly and
      complex tissue formation. 

PMID- 24310101
TI  - Persistent environmental pollutants and couple fecundity: an overview.
AB  - Speculation has arisen that human fecundity may be declining, possibly a function
      of exposure to persistent environmental chemicals that resist degradation
      resulting in various pathways for human exposure. In contrast to considerable
      animal evidence suggesting adverse effects of such chemicals on reproduction,
      limited human research has been undertaken. To date, available data stem largely
      from ten unique study cohorts that have quantified individual chemical exposures
      in relation to time-to-pregnancy (TTP), which is a measure of couple fecundity.
      Diminished fecundability odds ratios indicative of longer TTP were observed in
      all but two studies, although not all findings achieved statistical significance.
      Persistent chemicals associated with reduced couple fecundity as measured by a
      longer TTP included betaHCH, cadmium, lead, mercury, 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene, TCCD dioxin, and select polybrominated diethers,
      polychlorinated biphenyls, and perfluorochemicals. Important methodologic
      limitations need to be considered in weighing the evidence: i) reliance on
      pregnant women, which may exclude women with the highest exposures if related to
      the inability to conceive; ii) retrospectively reported TTP, which may be
      associated with bidirectional reporting errors; and iii) limited attention to
      male partners or couples' exposures. While current evidence is not inconsistent
      with animal evidence, concerted efforts to address lingering data gaps should
      include novel strategies for recruiting couples, the longitudinal measurement of
      TTP, and the continued enrollment of couples across successive pregnancies. This
      latter strategy will provide a more complete understanding of the toxicokinetics
      of chemicals during sensitive windows and their implications for fecundity and
      its related impairments. 

PMID- 24310102
TI  - Starting an automated dose dispensing service provided by community pharmacies in
      Finland.
AB  - BACKGROUND: In an automated dose dispensing (ADD) service, medicines are packed
      in unit-dose bags according to administration times. When the service is
      initiated, the patient's medication list is reconciled and the medication is
      reviewed on the basis of this list. OBJECTIVE: The aim of this national study was
      to investigate how the medication list was reconciled, what type of medication
      review was conducted, and what changes were made to the patient's medications
      when the ADD service is initiated. SETTING: Primary care in Finland. METHOD: All
      patients enrolled in the service during a 3-week period in autumn 2010 were
      included in the study. All community pharmacies (n = 267) purchasing unit-dose
      bags from Espoonlahti Pharmacy documented the actions taken in the ADD initiation
      process using a structured data collection sheet. MAIN OUTCOME MEASURE:
      Information sources needed in medication reconciliation, the type of medication
      review conducted and changes made to patients' medications. RESULTS:
      Documentation was completed for 147 out of 325 new ADD users resulting 45 % as a
      response rate. More than one source was needed for 63 % of the patients in
      medication reconciliation. The most common sources used were nursing staff (72 %
      of the patients) and an existing medication list (71 %). Some type of medication
      review, most commonly a prescription review, was conducted for the majority of
      the patients (96 %), usually in multi-professional collaboration. Treatment
      related changes were made for 43 % of the patients and technical changes were
      made for 93 % of the patients. CONCLUSION: The medication list was incomplete for
      more than half of the patients. Some type of medication review was conducted for
      most of the patients. Both treatment-related changes and technical changes were
      made on patients' medications during the initiation process. The start-up process
      of the ADD service needs further development to ensure a standard procedure and
      optimum use of resources.

PMID- 24310103
TI  - Adherence: the journey of medication taking, are we there yet?
AB  - Patient adherence to medications has been an issue challenging healthcare
      professionals for decades. Adherence rates, causes of non-adherence, barriers and
      enablers to medication taking, interventions to promote adherence, and the impact
      of non-adherence on health outcomes, have been extensively studied. In light of
      this, the area of adherence research has progressed conceptually and practically.
      This special issue contains a range of articles which focus on different aspects
      of adherence, from standardising terminology and methods of measurement, to non
      adherence in a broad range of patient populations, and to interventions to
      promote adherence. 

PMID- 24310104
TI  - Increasing urinary calcium excretion after ceftriaxone and cephalothin therapy in
      adults: possible association with urolithiasis.
AB  - In children, stone formation after ceftriaxone (CTRX) therapy by increasing
      calcium excretion was showed in the literature. In this study, we investigated
      the effect of CTRX, cephalothin (CP) and ampicillin (AS) therapy on urinary
      calcium excretion in adults. 180 participants included in the study who divided
      into six equal groups. The groups were; (1) CTRX therapy in stone free patients,
      (2) CTRX therapy in patients who have urinary stone; (3) CP therapy in stone free
      patients, (4) CP therapy in patients with urinary stone, (5) AS therapy in stone
      free patients, (6) AS therapy in patients with urinary stone. The patients
      received 2 g/day intravenous CTRX, CP and AS for 5 days in all groups
      respectively. There were no significant differences in demographic
      characteristics and blood biochemistry between the groups. Before and 5 days
      after the antibiotic therapies, the participants were evaluated by 24-h urinary
      calcium to creatinine ratio. Results were compared between the groups
      statistically by ANOVA and Tukey test. After drug therapies in group 2 and 4, the
      excretion of calcium to creatinine ratio in 24-h urine was more than the other
      groups. We found that both groups of two drugs therapy with or without stones
      (groups 1, 2, 3, 4), have significantly increased calcium to creatinine ratio in
      24-h urine (p < 0.05). We did not find statistically difference in groups 5 and
      6, after AS therapy. As a result of the study, we suggest that the patients who
      have taken antibiotic therapy with CTRX or CP, have an increased risk for the
      urolithiasis. In addition, we think that these drugs should be used carefully
      especially in patients with urolithiasis.

PMID- 24310105
TI  - Edge-exposed MoS2 nano-assembled structures as efficient electrocatalysts for
      hydrogen evolution reaction.
AB  - Edge-exposed MoS2 nano-assembled structures are designed for high hydrogen
      evolution reaction activity and long term stability. The number of sulfur edge
      sites of nano-assembled spheres and sheets is confirmed by Raman spectroscopy and
      EXAFS analysis. By controlling the MoS2 morphology with the formation of nano
      assembled spheres with the assembly of small-size fragments of MoS2, the
      resulting assembled spheres have high electrocatalytic HER activity and high
      thermodynamic stability. 

PMID- 24310106
TI  - Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase (DPD)
      splice site variant: the need for further revision of dose and schedule.

PMID- 24310107
TI  - The predictors of foot ulceration in patients with rheumatoid arthritis.
AB  - This study was conducted to determine the predictors of foot ulceration occurring
      in patients with rheumatoid arthritis (RA) without diabetes. A multi-centre case
      control study was undertaken; participants were recruited from eight sites (UK).
      Cases were adults diagnosed with RA (without diabetes) and the presence of a
      validated foot ulcer, defined as a full thickness skin defect occurring in
      isolation on / below the midline of the malleoli and requiring > 14 days to heal.
      Controls met the same criteria but were ulcer naive. Clinical examination
      included loss of sensation (10g monofilament); ankle-brachial pressure index
      (ABPI); forefoot deformity (Platto); plantar pressures (PressureStat); RA disease
      activity (36 swollen/tender joint counts) and the presence of vasculitis. History
      taking included past ulceration/foot surgery; current medication and smoking
      status. Participants completed the Health Assessment Questionnaire (HAQ) and Foot
      Impact Scale. A total of 83 cases with 112 current ulcers and 190 ulcer naive
      controls participated. Cases were significantly older (mean age 71 years; 95 %
      confidence interval [CI], 69-73 vs. 62 years, 60-64) and had longer RA disease
      duration (mean 22 years; 19-25 vs. 15, 13-17). Univariate analysis showed that
      risk of ulceration increases with loss of sensation; abnormality of ABPI and foot
      deformity. Plantar pressures and joint counts were not significant predictors.
      HAQ score and history of foot surgery were strongly associated with ulceration
      (odds ratio [OR] = 1.704, 95 % CI 1.274-2.280 and OR = 2.256, 95 % CI 1.294
      3.932). Three cases and two controls presented with suspected cutaneous
      vasculitis. In logistic regression modelling, ABPI (OR = 0.04; 95 % CI, 0.01
      0.28) forefoot deformity (OR = 1.14; 95 % CI, 1.08-1.21) and loss of sensation
      (OR = 1.22; 95 % CI, 1.10-1.36) predicted risk of ulceration. In patients with
      RA, ABPI, forefoot deformity and loss of sensation predict risk of ulceration
      but, in contrast with diabetes, raised plantar pressures do not predict risk. 

PMID- 24310108
TI  - The characteristics of patients having ankylosing spondylitis associated with
      Takayasu's arteritis.
AB  - Both ankylosing spondylitis (AS) and Takayasu's arteritis (TA) are infrequent,
      and their association is even more rare. Our objective was to assess their
      association and characteristics in our patients. We conducted retrospective
      analysis of our hospital inpatients from June 2000 to July 2011 who had both AS
      and TA. We used modified New York criteria for ankylosing spondylitis (1984) as
      AS diagnosis criterion and American College of Rheumatology Classification
      Criteria for Takayasu's Arteritis as TA diagnosis criterion. All clinical data,
      lab data, and radiological data were collected. Six patients were included in our
      study because they fulfilled our AS and TA criteria, four males and 2 females,
      aged from 18 to 35 years old. Four patients were HLA-B27 positive and 2 were
      negative. All patients' inflammatory markers such as erythrocyte sedimentation
      rate and C-reactive protein were high. The clinical characteristics of patients
      with both diseases did not seem to be different from that of patients with AS or
      TA alone in China. All patients were first diagnosed as AS, then found TA 3-20
      years later. After diagnosed those patients having AS and TA, patients were given
      prednisone and cyclophosphamide and their symptoms improved gradually. Our study
      provides further evidence of the association of TA with AS. We should know that
      some AS patients can do have TA. To AS patients who have fever, bruit, or
      pulselessness, we should suspect that they have TA.

PMID- 24310109
TI  - Low-dose aspirin and survival in men with prostate cancer: a study using the UK
      Clinical Practice Research Datalink.
AB  - PURPOSE: Aspirin use is associated with reduced risk of, and death from, prostate
      cancer. Our aim was to determine whether low-dose aspirin use after a prostate
      cancer diagnosis was associated with reduced prostate cancer-specific mortality.
      METHODS: A cohort of newly diagnosed prostate cancer patients (1998-2006) was
      identified in the UK Clinical Practice Research Datalink (confirmed by cancer
      registry linkage). A nested case-control analysis was conducted using conditional
      logistic regression to compare aspirin usage in cases (prostate cancer deaths)
      with up to three controls (matched by age and year of diagnosis). RESULTS: Post
      diagnostic low-dose aspirin use was identified in 52 % of 1,184 prostate cancer
      specific deaths and 39 % of 3,531 matched controls (unadjusted OR 1.51, 95 % CI
      1.19, 1.90; p < 0.001). After adjustment for confounders including treatment and
      comorbidities, this association was attenuated (adjusted OR  1.02 95 % CI 0.78,
      1.34; p = 0.86). Adjustment for estrogen therapy accounted for the majority of
      this attenuation. There was also no evidence of dose-response association after
      adjustments. Compared with no use, patients with 1-11 prescriptions and 12 or
      more prescriptions had adjusted ORs of 1.07 (95 % CI 0.78, 1.47; p = 0.66) and
      0.97 (95 % CI 0.69, 1.37; p = 0.88), respectively. There was no evidence of a
      protective association between low-dose aspirin use in the year prior to
      diagnosis and prostate cancer-specific mortality (adjusted OR 1.04 95 % CI 0.89,
      1.22; p = 0.60). CONCLUSION: We found no evidence of an association between low
      dose aspirin use before or after diagnosis and risk of prostate cancer-specific
      mortality, after potential confounders were accounted for, in UK prostate cancer
      patients.

PMID- 24310110
TI  - Lessons from ECLIPSE: a review of COPD biomarkers.
AB  - The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points
      (ECLIPSE) study was a large 3-year observational controlled multicentre
      international study aimed at defining clinically relevant subtypes of chronic
      obstructive pulmonary disease (COPD) and identifying novel biomarkers and genetic
      factors. So far, the ECLIPSE study has produced more than 50 original
      publications and 75 communications to international meetings, many of which have
      significantly influenced our understanding of COPD. However, because there is not
      one paper reporting the biomarker results of the ECLIPSE study that may serve as
      a reference for practising clinicians, researchers and healthcare providers from
      academia, industry and government agencies interested in COPD, we decided to
      write a review summarising the main biomarker findings in ECLIPSE. 

PMID- 24310111
TI  - Uncommon delayed and late complications after percutaneous left atrial appendage
      closure with Amplatzer((r)) Cardiac Plug.
AB  - AIMS: Percutaneous left atrial appendage closure with Amplatzer((r)) Cardiac Plug
      (St. Jude Medical Inc.) for the prevention of stroke in patients with atrial
      fibrillation is rapidly propagating. We sought to provide additional safety data.
      METHODS AND RESULTS: We have screened our database of patients having been
      treated with Amplatzer((r)) Cardiac Plug and found 3 cases with uncommon
      complications that have not been reported previously. One patient experienced an
      embolisation of the occluder about 12 months after implantation that potentially
      resulted from mismatch of occluder size and landing zone. Another patient
      developed cardiac tamponade 9 days after implantation. This case of delayed
      effusion was probably not a result of interventional trauma, but might have been
      provoked by scratching of the inner pericardial membrane. A third patient
      developed a large thrombus in the left atrium which was considered to be caused
      by injury of the endothelial wall during implantation. The first two cases could
      be treated by a percutaneous procedure, the last case by cardiac surgery without
      any sequelae. CONCLUSIONS: Complications after left atrial appendage closure not
      related to a device-related thrombus can occur later after implantation. With
      appropriate percutaneous or surgical management these complications can be
      handled without sequelae.

PMID- 24310112
TI  - The role of enzyme activation state in limiting carbon assimilation under
      variable light conditions.
AB  - The mechanisms regulating transient photosynthesis by soybean (Glycine max)
      leaves were examined by comparing photosynthetic rates and carbon reduction cycle
      enzyme activities under flashing (saturating 1 s lightflecks separated by low
      photon flux density (PFD) periods of different durations) and continuous PFD. At
      the same mean PFD, the mean photosynthetic rates were reduced under flashing as
      compared to continuous light. However, as the duration of the low PFD period
      lengthened, the CO2 assimilation attributable to a lightfleck increased. This
      enhanced lightfleck CO2 assimilation was accounted for by a greater
      postillumination CO2 fixation occurring after the lightfleck. The induction state
      of photosynthesis, ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco),
      fructose 1,6-bisphosphatase (FBPase) and ribulose 5-phosphate kinase (Ru5P
      kinase) activities all responded similarly and were all lower under flashing as
      compared to constant PFD of the same integrated mean value. However, the fast
      phase of induction and FBPase and Ru5P kinase activities were reduced more than
      were the slow phase of induction and rubisco activity. This was consistent with
      the role of the former enzymes in the fast induction component that limited RuBP
      regeneration. Competition for reducing power between carbon metabolism and
      thioredoxin-mediated enzyme activation may have resulted in lower enzyme
      activation states and hence lower induction states under flashing than continuous
      PFD, especially at low lightfleck frequencies (low mean PFD). 

PMID- 24310113
TI  - Changes in the antenna size of Photosystem I and Photosystem II in Synechococcus
      sp. strain PCC 7942 grown in the presence of SANDOZ 9785 - a Photosystem II
      inhibitor.
AB  - SANDOZ 9785, also known as BASF 13.338, is a pyridazinone derivative that
      inhibits Photosystem II (PS II) activity leading to an imbalance in the rate of
      electron transport through the photosystems. Synechococcus sp. strain PCC 7942
      cells grown in the presence of sublethal concentration of SANDOZ 9785 (SAN 9785)
      for 48 hours exhibited a 20% decrease in Chl a per cell. However, no changes were
      observed in the content of phycocyanin per cell, the size of the phycobilisomes
      or in the PS II:PS I ratio. From an estimate of PS II electron transport rate
      under varying light intensities and spectral qualities and analysis of room
      temperature Chl a fluorescence induction, it was deduced that growth of
      Synechococcus PCC 7942 in the presence of SAN 9785 leads to a redistribution of
      excitation energy in favour of PS II. Though the redistribution appears to be
      primarily caused by changes affecting the Chl a antenna of PS II, the extent of
      energetic coupling between phycobilisomes and PS II is also enhanced in SAN 9785
      grown Synechococcus PCC 7942 cells. There was a reduction in the effective size
      of PS I antenna based on measurement of P700 photooxidation kinetics. These
      results indicate that when PS II is partially inhibited, the structure of
      photosynthetic apparatus alters to redistribute the excitation energy in favour
      of PS II so that the efficiency of utilization of light energy by the two
      photosystems is optimized. Our results suggest that under the conditions used,
      drastic structural changes are not essential for redistribution of excitation
      energy between the photosystems. 

PMID- 24310114
TI  - Grana stacking and protection of Photosystem II in thylakoid membranes of higher
      plant leaves under sustained high irradiance: An hypothesis.
AB  - We propose yet another function for the unique appressed thylakoids of grana
      stacks of higher plants, namely that during prolonged high light, the non
      functional, photoinhibited PS II centres accumulate as D1 protein degradation is
      prevented and may act as dissipative conduits to protect other functional PS II
      centres. The need for this photoprotective mechanism to prevent high D1 protein
      turnover under excess photons in higher plants, especially those grown in shade,
      is due to conflicting demands between efficient use of low irradiance and
      protection from periodic exposure to excessive irradiance. 

PMID- 24310115
TI  - The photoproduction of superoxide radicals and the superoxide dismutase activity
      of Photosystem II. The possible involvement of cytochrome b559.
AB  - In the present study the light induced formation of superoxide and intrinsic
      superoxide dismutase (SOD) activity in PS II membrane fragments and D1/D2/Cytb559
      complexes from spinach have been analyzed by the use of ferricytochrome c (cyt
      c(III)) reduction and xanthine/xanthine oxidase as assay systems. The following
      results were obtained: 1.) Photoreduction of Cyt c (III) by PS II membrane
      fragments is induced by addition of sodium azide, tetracyane ethylene (TCNE) or
      carbonylcyanide-p-trifluoromethoxy-phenylhydrazone (FCCP) and after removal of
      the extrinsic polypeptides by a 1M CaCl2-treatment. This activity which is absent
      in control samples becomes completely inhibited by the addition of exogenous SOD.
      2.) The TCNE induced cyt c(III) photoreduction by PS II membrane fragments was
      found to be characterized by a half maximal concentration of c1/2=10 MUM TCNE.
      Simultaneously, TCNE inhibits the oxygen evolution rate of PS II membrane
      fragments with c1/2~ 3 MUM. 3.) The photoproduction of O2 (-) is coupled with
      H(+)-uptake. This effect is diminished by the addition of the O2 (-)-trap cyt
      c(III). 4.) D1/D2/Cytb559-complexes and PS II membrane fragments deprived of the
      extrinsic proteins and manganese exhibit no SOD-activity but are capable of
      producing O2 (-) in the light if a PS II electron donor is added.Based on these
      results the site(s) of light induced superoxide formation in PS II is (are)
      inferred to be located at the acceptor side. A part of the PS II donor side and
      Cyt b559 in its HP-form are proposed to provide an intrinsic superoxide dismutase
      (SOD) activity. 

PMID- 24310116
TI  - Spectral changes of the B800-850 antenna complex from Ectothiorhodospira sp.
      induced by detergent and salt treatment.
AB  - We have studied the effects of the detergent lauryl dimethylamine N-oxide and
      NaCl in the near infrared absorption spectra of the B800-850 antenna complex from
      Ectothiorhodospira sp. Strong spectral changes were induced on the BChl850 band
      by the lauryl dimethylamine N-oxide consisting of a blue shift, from 857 to 839
      837 nm, and a hypochromism. No significant effects were detected on the BChl800
      band in the same conditions. The changes were reversible after removing most of
      the detergent from the sample. Depending upon the detergent concentration in the
      solution, NaCl was also able to reverse the blueshift and increase the intensity
      of the 850 nm band close to the native values. Moreover, we have been able to
      separate both phenomena. Addition of 0.350 M NaCl after sample incubation with
      0.15% (v/v) lauryl dimethylamine N-oxide for 30 min allowed a 9-10 nm redshift
      with no significant hyperchromism of the lowest energy band. We explained the
      overall effect of the detergent assuming that the lauryl dimethylamine N-oxide
      bound to the hydrophobic moiety of the complex and caused some protein
      conformational changes which affected the BChl850 domain without affecting that
      of the BChl800. The NaCl was able to circumvent these effects, most probably by
      acting directly on the BChl850 molecules or on the protein structure surrounding
      them. 

PMID- 24310118
TI  - Non-photochemical fluorescence quenching and the diadinoxanthin cycle in a marine
      diatom.
AB  - The diadinoxanthin cycle (DD-cycle) in chromophyte algae involves the
      interconversion of two carotenoids, diadinoxanthin (DD) and diatoxanthin (DT). We
      investigated the kinetics of light-induced DD-cycling in the marine diatom
      Phaeodactylum tricornutum and its role in dissipating excess excitation energy in
      PS II. Within 15 min following an increase in irradiance, DT increased and was
      accompanied by a stoichiometric decrease in DD. This reaction was completely
      blocked by dithiothreitol (DTT). A second, time-dependent, increase in DT was
      detected ~ 20 min after the light shift without a concomitant decrease in DD. DT
      accumulation from both processes was correlated with increases in non
      photochemical quenching of chlorophyll fluorescence. Stern-Volmer analyses
      suggests that changes in non-photochemical quenching resulted from changes in
      thermal dissipation in the PS II antenna and in the reaction center. The increase
      in non-photochemical quenching was correlated with a small decrease in the
      effective absorption cross section of PS II. Model calculations suggest however
      that the changes in cross section are not sufficiently large to significantly
      reduce multiple excitation of the reaction center within the turnover time of
      steady-state photosynthetic electron transport at light saturation. In DTT
      poisoned cells, the change in non-photochemical quenching appears to result from
      energy dissipation in the reaction center and was associated with decreased
      photochemical efficiency. D1 protein degradation was slightly higher in samples
      poisoned with DTT than in control samples. These results suggest that while DD
      cycling may dynamically alter the photosynthesis-irradiance response curve, it
      offers limited protection against photodamage of PS II reaction centers at
      irradiance levels sufficient to saturate steady-state photosynthesis. 

PMID- 24310117
TI  - Active-site histidines in recombinant cyanobacterial ribulose-1,5-bisphosphate
      carboxylase/oxygenase examined by site-directed mutagenesis.
AB  - The functions of His(291), His(295) and His(324) at the active-site of
      recombinant A. nidulans ribulose-1,5-bisphosphate carboxylase/ oxygenase have
      been explored by site-directed mutagenesis. Replacement of His(291) by K or R
      resulted in unassembled proteins, while its replacement by E, Q or N resulted in
      assembled but inactive proteins. These results are in accord with a metal ion
      binding role of this residue in the activated ternary complex by analogy to x-ray
      crystallographic analyses of tobacco and spinach enzymes.His(324) (H327 in
      spinach), which is located within bonding distance of the 5-phosphate of bound bi
      substrate analog 2-carboxyarabinitol 1,5-bisphosphate in the crystal structures,
      has been substituted by A, K, R, Q and N. Again with the exception of the H324K
      and R variants, these changes resulted in detectable assembled protein. The
      mutant H324A protein exhibited no detectable carboxylase activity, whereas the
      H324Q and H324N changes resulted in purifiable holoenzyme with 2.0 and 0.1% of
      the recombinant wild-type specific carboxylase activity, respectively. These
      results are consistent with a phosphate binding role for this residue.The
      replacement of His(295), which has been suggested to aid in phosphate binding,
      with Ala in the A. nidulans enzyme leads to a mutant with 5.8% of the recombinant
      wild-type carboxylase activity. All other mutations at this position resulted in
      unassembled proteins. Purified H295A and H324Q enzymes had elevated Km(RuBP)
      values and unchanged CO2/O2 specificity factors compared to recombinant wild
      type. 

PMID- 24310119
TI  - Cystic fibrosis epithelial cell and bacterial binding.

PMID- 24310120
TI  - Cystic fibrosis epithelial cell and bacterial binding.

PMID- 24310121
TI  - Factors other than root secreted malic acid that contributes toward Bacillus
      subtilis FB17 colonization on Arabidopsis roots.
AB  - The plant growth promoting rhizobacterium (PGPR) Bacillus subtilis FB17
      (hereafter FB17) induces resistance against broad pathogen including Pseudomonas
      syringae pv tomato (PstDC3000). The extent of plant protection by FB17 depends on
      establishment of root colonization followed by biofilm formation. The general
      convention dictates that beneficial rhizobacterium may suppress the root innate
      immune system to establish a robust colonization. However, it is still not well
      understood which genetic targets FB17 affects in plants to facilitate a symbiotic
      association. Our recent study, involving whole transcriptome analysis of
      Arabdiopsis thaliana roots treated with FB17 post 24 h of treatment showed
      totally 279 genes that were significantly up- or/ downregulated. Further, we
      found that the mutants for upregulated and downregulated genes post-FB17
      colonization showed a differential phenotype for FB17 root colonization.
      Interestingly, plants mutated in the FB17-responsive genes showed increased
      Aluminum activated malate transporter (ALMT1) expression under foliar pathogen
      PstDC3000, infections, indicating the independent functionality of ALMT1 for
      bacterial recruitment. Taken together this, present study suggests that the
      establishment of interaction between the plant host and PGPR is a complex
      phenomenon which is regulated by multiple genetic components. 

PMID- 24310122
TI  - Inhibition of barnacle settlement and behavior by natural products from whip
      corals,Leptogorgia virgulata (Lamarck, 1815).
AB  - Laboratory-reared barnacle larvae were used to study natural products from whip
      corals. Biological assays used barnacle responses in behavioral assays and in
      larval settlement assays. Whip corals contained substances that were active in
      both assays. Substances inhibiting swimming and reversible attachment of barnacle
      larvae were found in an aqueous extract of whip corals. Low-molecular-weight
      substances inhibiting barnacle settlement were found in a methylene chloride
      extract of material soluble in aqueous methanol. Antisettlement activity was
      associated with substances with specific mobilities in several chromatography
      systems. Partially purified material was effective in preventing settlement at
      concentrations of less than 0.2 MU/ml. Settlement inhibition involves adsorption
      of the natural product to surfaces. 

PMID- 24310123
TI  - Attractancy toOryzaephilus surinamensis (L.) of volatile materials isolated from
      vacuum distillate of heat-treated carobs.
AB  - Vacuum distillation of heat-treated carobs gave an aqueous, colorless, sweet
      smelling distillate which was tested over a wide range of concentrations and
      found to be highly attractive to adultOryzaephilus surinamensis (L.). The
      materials responsible for the aroma were isolated from the distillate by
      saturating with sodium chloride and extracting into diethyl ether as separate
      acidic, neutral, and basic fractions. The extraction efficiency was checked by
      recombining portions of the three fractions and replacing the diethyl ether with
      water to give a "reconstituted distillate;" this was almost as attractive as the
      original distillate. Bioassay of aqueous solutions of the three separate
      fractions showed that the acidic was attractive, while the neutral and basic had
      little effect. The five major components of the acidic fraction were found to be
      acetic, isobutyric,n-butyric, 2-methylbutyric, and hexanoic (caproic) acids.
      Bioassay of these in aqueous solution, both separately and combined, showed that
      hexanoic acid was the most attractive and may be responsible for both the longer
      lasting attractive effect of the carob distillate and for the effectiveness of
      carobs themselves used in bait bags to detect stored product insects. 

PMID- 24310124
TI  - Allelopathic effects of giant foxtail on germination and radicle elongation of
      loblolly pine seed.
AB  - Water extracts of giant foxtail grass inhibited germination and radicle
      elongation of loblolly pine seed in a laboratory test. Most of the toxic effects
      came from extracts of dried foxtail tops, with lesser amounts from fresh tops and
      roots. Soil texture affected the phytotoxicity of the extracts. Eight chemical
      compounds known to be phytotoxins inSetaria were identified in extracts of
      foxtail leaves but could not be found in soil samples under the leaves. 

PMID- 24310125
TI  - Chemical investigations of wolf (Canis lupus) anal-sac secretion in relation to
      breeding season.
AB  - The volatile constituents of wolf anal-sac secretions were examined via capillary
      gas chromatography and compared among intact males, females, castrate males,
      ovariectomized females, and anosmic and pinealectomized males and females. Some
      chemical compounds were deemed significantly different (t test, 95% confidence
      level) among the groups both during and outside of the mating season, implying
      that the volatile components of anal-sac secretion can be used to communicate
      information regarding gender or endocrine state. As a result of treating the anal
      sac with antibiotics, some of these compounds, including 1-octen-3-ol and indole,
      were implicated as being products of microbial action. In addition, short-chain
      carboxylic acids were investigated and essentially no significant variations were
      seen among the groups. 

PMID- 24310126
TI  - Influence ofAmaranthus hybridus L. allelochemics on oviposition behavior
      ofSpodoptera exigua andS. eridania (Lepidoptera: Noctuidae).
AB  - Common pigweed,Amaranthus hybridus L., is a favorite host of the beet army worm
      (BAW),Spodoptera exigua L. Chemicals extracted from homogenized pigweed with
      distilled water, ethanol, or dichloromethane and sprayed back on pigweed deterred
      oviposition by the BAW. Similarly, water extracts of frass from conspecific
      larvae or southern armyworm (SAW) larvae,S. eridania (Cramer), fed pigweed leaves
      and sprayed back on pigweed plants also deterred BAW oviposition, thus confirming
      that deterrence was due to plant allelochemics rather than specific compounds
      associated with the metabolic or excretory products of the larvae. Confirmation
      of the presence of oviposition-deterring chemicals in pigweed was used to explain
      a previously observed seasonal displacement of BAW by SAW on pigweed in the
      field. 

PMID- 24310127
TI  - Effects of various mixtures of ferulic acid and some of its microbial metabolic
      products on cucumber leaf expansion and dry matter in nutrient culture.
AB  - Cucumber seedlings (Cucumis sativus cv. 'Early Green Cluster') ranging from 6 to
      16 days of age were treated with various concentrations (0- 1 mM) of caffeic,
      ferulic,p-coumaric,p-hydroxybenzoic, protocatechuic, sinapic, syringic, and
      vanillic acids and mixtures of ferulic acid and one or two of the other phenolic
      acids. Seedlings were grown in full-strength Hoagland's solution which was
      changed every other day. Phenolic acid treatments were given with each nutrient
      solution change starting at day 6 or given once when seedlings were 13 or 14 days
      old. Leaf area, mean relative rates of leaf expansion, transpiration rates, water
      utilization, and the concentrations of the phenolic acids in nutrient solution
      were determined at one- or two-day intervals. Seedling dry weight was determined
      at final harvest. Seedling leaf area and dry weight were linearly related. Since
      leaf areas can be easily obtained without destructive sampling and leaf area
      expansion responds rapidly to phenolic acid treatments, it was utilized as the
      primary indicator of plant response. The resulting data suggested that a number
      of ferulic acid microbial metabolic products, as well as two other phenolic acids
      observed in soils (p-coumaric and syringic acid), can reduce seedling dry weight,
      leaf expansion, and water utilization of cucumber seedlings in a similar manner.
      The magnitude of impact of each of the phenolic acids, however, varied with
      phenolic acid and concentration. It appears that the inhibitory activity of these
      phenolic acids involved water relations of cucumber seedlings, since the phenolic
      acid treatments resulted in closure of stomata which then remained closed for
      several days after treatment. The data also demonstrated that the effects of
      mixtures of phenolic acids on cucumber seedlings may be synergistic, additive, or
      antagonistic. The type of response observed appeared to be related to the factor
      measured, the compounds in the nmixture, and the magnitued of inhibition
      associated with each compounds. The data also indicated that the effects of the
      various phenolic acids were reversible, since seedling leaf area increased
      rapidly once phenolic acids were removed from the root environment. Mean relative
      rates of leaf expansion recovered even in the presence of the various phenolic
      acids. 

PMID- 24310128
TI  - Absolute configuration of mosquito oviposition attractant pheromone, 6-acetoxy-5
      hexadecanolide.
AB  - 6-Acetoxy-5-hexadecanolide (Ia) in the oviposition attractant pheromone released
      from egg apical droplets of the mosquitoCulex pipiens fatigans Wied. is shown to
      be the (-)-(5R,6S)- enantiomer. Identification was by chromatography of the 6
      trifluoroacetoxy derivatives of the natural pheromone and of the synthetic (-)
      (5R,6S)- (Ib) and (+)-(5S,6R)- (IIb) enantiomers on a capillary column having a
      chiral stationary phase comprising a derivative of (1S,3S)-chrysanthemic acid.
      The synthetic (-)-(5R,6S)- enantiomer (Ia) attracted oviposition of four fold
      more mosquito egg rafts than the control (P < 0.01) whereas for the (5S,6R)-
      enantiomer (IIa) there was no statistically significant oviposition attraction. 

PMID- 24310129
TI  - Sex pheromones and reproductive isolation in four european small ermine moths.
AB  - Reproductive isolation among four sympatric small ermine moths (Yponomeuta) is
      analyzed in terms of niches in the sexual communication channel. Potential
      pheromone components were identified from pheromone gland secretions ofY.
      evonymellus,Y. cagnagellus,Y. padelius, andY. vigintipunctatus by gas
      chromatography with flame ionization and electroantennographic detection and
      tested for behavioral activity in the field. The species were found to share (Z)
      11-tetradecenyl acetate (Z11-14: OAc) in combination with varying proportions of
      theE isomer as primary sex pheromone components.Y. cagnagellus differs from the
      rest of the species by having only a small amount (1.5%) ofE isomer relative toZ
      isomer in its pheromone. The closely relatedY. padelius has a three-component
      pheromone including large amounts (ca. 400%) of (Z)-11-hexadecenyl acetate (Z11
      16:OAc) in addition toZ11-14: OAc (100%) andE11-14: OAc (34%).Z11-16: OAc appears
      to reduce trap catches ofY. evonymellus andY. vigintipunctatus when added to the
      pheromone. Although these species are the two most distantly related European
      small ermine moths, they seem to share the same sex pheromone, i.e.,Z11-14?OAc
      (+20%E) and (Z)-11-tetradecenol. Our interpretation is that this might have been
      the sex pheromone of the ancestor of today'sYponomeuta species. 

PMID- 24310130
TI  - Selective sequestration of milkweed (Asclepias sp.) cardenolides inOncopeltus
      fasciatus (Dallas) (Hemiptera: Lygaeidae).
AB  - The cardenolide content of the gut, wings, and fat body ofOncopeltus fasciatus
      was examined. The female fat body contained 4-5% of the total cardenolide content
      of the insect. The cardenolide content of male fat body, and gut and wings of
      both sexes was below the detection limit of the cardenolide assay. Thin-layer
      chromatography was used to determine the cardenolide array of various tissues and
      secretions ofO. fasciatus reared on seeds of a single species of milkweed (A.
      Speciosa) and adult extracts and dorsolateral space fluid ofO. fasciatus reared
      on seeds of two species of milkweed with different cardenolide arrays (A.
      speciosa andA. syriaca). Our results indicate that cardenolides are not
      sequestered in the insect simply on the basis of polarity and that metabolism and
      differential excretion of cardenolides are involved in the sequestration of
      cardenolides inO. fasciatus. The similarities in the cardenolide profiles ofO.
      fasciatus reared on different food sources, and tissues ofO. fasciatus reared on
      a single food source indicates that there is regulation of the cardenolide array
      inO. Fasciatus. 

PMID- 24310131
TI  - Characterization of inhibitors of cellulose synthesis in cotton fibers.
AB  - Several compounds were tested for their ability to inhibit the in-vivo synthesis
      of cellulose and other cell-wall polysaccharides in fibers of cotton (Gossypium
      hirsutum L.) developing on in-vitro cultured ovules. Inhibitory effects were
      measured by the ability of the compounds to inhibit the incorporation of
      radioactivity from [U-(14)C]glucose into these cell-wall polymers. Of the
      compounds surveyed, 2,6-dichlorobenzonitrile (DCB) was the most effective and
      specific one for its effects on cellulose synthesis when compared to its effect
      on the synthesis of other cell-wall components. At 10 MUM DCB caused 80%
      inhibition of cellulose synthesis, and the effect was reversed upon removal of
      the DCB, with recovery to 90% of the control rate. Two analogs of DCB, 2-chloro-6
      fluorobenzonitrile and 2,6-dichlorobenzene carbothiamide, were as specific and
      nearly as effective as DCB with respect to their effects on cellulose synthesis.
      Coumarin, generally regarded as an inhibitor of cellulose synthesis in other
      plant systems, was effective in cotton fibers in millimolar concentrations and,
      like DCB, was relatively specific with regard to its effect on cellulose
      synthesis. DCB and coumarin inhibited the synthesis of both primary and secondary
      wall cellulose. Bacitracin, an inhibitor of the cycling of phosphorylated
      polyprenols involved in cell-wall synthesis in bacteria, and
      ethylenediaminetetracetic acid (EDTA) and ethyleneglycol-bis-(beta-amino
      ethylether)-N,N'-tetracetic acid (EGTA), chelators of civalent cations, were also
      effective, although only at relatively high concentrations, in inhibiting
      incorporation of radioactivity into cellulose. 

PMID- 24310132
TI  - The presence of phytochrome in purified barley etioplasts and its in vitro
      regulation of biologically-active gibberellin levels in etioplasts.
AB  - Data are presented confirming that purified barley etioplasts contain, or have
      associated with them, consistently detectable amounts of photoreversible
      phytochrome. Etioplasts, separated from mitochondrial contamination by sucrose
      gradient centrifugation, respond in vitro to red light treatment by an increase
      in the level of extractable gibberellin-like substances. It is concluded that
      earlier reports of the substances. It is concluded that earlier reports of the
      phytochrome regulation of biologically-active gibberellin levels in crude plastid
      fractions represent responses of the etioplast alone. 

PMID- 24310133
TI  - Chloroplast DNA from three archegoniates.
AB  - 1. DNA from female and male Sphaerocarpos donnellii (liverwort) plants exhibits
      at least two species with buoyant densities of 1.703 (main band) and 1.691
      (satellite) g cm(-3) in CsCl equilibrium gradients. At least part, if not all, of
      the satellite DNA is localized in plastids. It consists of up to 90% of uniformly
      sized circular molecules of an average circumference of 38.5 MUm. Compared to
      other Chlorophyta, the liverwort's cpDNA is unusually low both in diensity and
      contour length. - 2. On the hand, cpDNA from the ferns Asplenium nidus and Pteris
      vittata resembles those of higher plants in buoyant density (1.697 g cm(-3)) and
      circumference (about 44.8 MUm). - 3. Analysis of DNA from the archegoniate
      chloroplasts with restriction endonucleases indicates chat the cyclic molecules
      are monomers. - 4. The results show that the circular molecules found in cpDNA of
      higher plants do not represent the functionally required minimum size of DNA in
      plastids. 

PMID- 24310134
TI  - Cuticular wax of wheat : The effects of chromosomal deficiencies on the
      biosynthesis of wax components.
AB  - n-Alkanes, esters, aldehydes, free alcohols, beta-diketones and hydroxy-beta
      diketones were found to be the lipid components of the cuticular waxes of common
      wheat Chinese Spring (Triticum aestivum L.). The ditelosomic lines 7A-L and 7D-S
      showed a dramatic decrease in the amount of beta-diketones and hydroxy beta
      diketones which are reduced to traces. The homologue composition within each
      class of compounds has also been determined for all three of the lines of wheat.
      The effects of chromosomal deficiencies have been demonstrated. Chromatographic
      techniques and mass spectrometry have been used for the separation and
      identification of the substances which compose the waxes. This study has provided
      further evidence of the role of genes situated on well defined chromosomes in
      determining the nature of classes of compounds composing wax and governing the
      homologous composition within each class of substances. 

PMID- 24310135
TI  - Polyamines and nucleic acids during the first cell cycle of Helianthus tuberosus
      tissue after the dormancy break.
AB  - Polyamines (spermine, spermidine, and putrescine) and nucleic acids were studied
      during the first cell cycle after the break of dormancy of tuber slices of
      Helianthus tuberosus L., cv. OB1. Immediately after the break of dormancy, a
      marked decrease in stored arginine and glutamine and a corresponding increase of
      polyamines were observed. This first synthesis of polyamines were observed. This
      firs synthesis of polyamines occurred very early during the G1 phase, concomitant
      to the synthesis of RNAs. A RNA, probably messenger-like RNA, was synthesized
      very actively only during the first hours of activation in the culture medium
      plus 2,4-dichlorophenoxyacetic acid, or in water. At the onset of the S phase,
      after 12h of activation, an incorporation of [(3)H] thymidine was also detected.
      A second putrescine synthesis and polyamine accumulation began during the
      progression of the S phase. During the progression of mitosis, there was a
      decrease of polyamine synthesis and accumulation. 

PMID- 24310136
TI  - Effects of combined nitrogen on anapleurotic carbon assimilation and bleeding sap
      composition in Phaseolus vulgaris L.
AB  - Dwarf french beans, Phaseolus vulgaris L., were grown with or without inoculation
      with rhizobia (strain 3644), and with or without a combined nitrogen source
      (nitrate or ammonium ions). The distribution of radioactivity into products of
      dark (14)CO2 assimilation was studied in roots or nodules from these plants. A
      detailed study was also made of the distribution and rates of excretion of
      nitrogen in xylem bleeding sap in 28 day old plants grown on the various sources
      of nitrogen. Whereas detached nodules accumulated radioactive glycine, serine and
      glutamate when incubated with (14)CO2, bleeding sap from plants root fed (14)CO2
      contained low levels of radioactivity in these compounds but higher levels in
      allantoin. Chemical analysis showed allantoin to be the major compound
      transported in the xylem of nodulated plants, whether or not they were fed on
      combined nitrogen. In contrast uninoculated plants accumulated mainly amino acids
      in the bleeding sap, the amount and chemical composition of which depended on the
      combined nitrogen source. 

PMID- 24310137
TI  - Analysis of DNA associated with nucleosomes in pea chromatin.
AB  - Micrococcal nuclease digestion of chromatin from ungerminated and 48 h-germinated
      pea embryos yields DNA fragments which are multiples of basic units of 194-195
      base pairs. Extensive digestion produces a core particle of 145 base pairs.
      Deoxyribonuclease I gives rise to fragments which are multiples of 10 bases upon
      analysis on denaturing gels. These values are comparable with those found for
      other plant materials. These results indicate that gross changes in nucleosomal
      organization do not accompany the onset of germination. 

PMID- 24310138
TI  - Two forms of alpha-glucosidase from sugar-beet seeds.
AB  - Two forms of alpha-glucosidase (EC 3.2.1.20), designated as I and II, have been
      isolated from sugarbeet (Beta vulgaris L.) seeds by a procedure including
      fractionation with ammonium sulfate and ethanol, carboxymethyl-cellulose column
      chromatography, and preparative disc gel electrophoresis. The two enzymes were
      homogeneous by polyacrylamide disc gel electrophoresis. Their molecular weights
      were 98,000 (I) and 60,000 (II). alpha-Glucosidase I readily hydrolyzed maltose,
      isomaltose, kojibiose, maltotriose, panose, amylose, soluble starch, amylopectin
      and glycogen. alpha-Glucosidase II also hydrolyzed maltose, kojibiose and
      maltotriose but hydrolyzed the other substrates only very weakly or not at all.
      alpha-Glucosidase I hydrolyzed soluble starch at a faster rate than maltose. It
      produced isomaltose and panose as the main alpha-glucosyltransfer products from
      maltose, whereas maltotriose was the main product of alpha-glucosidase II. alpha
      Glucosidase I hydrolyzed amylose liberating alpha-glucose. The neutral-sugar
      content was calculated to be 2.7% for alpha-glucosidase I and 8.8% for alpha
      glucosidase II. The main neutral sugar was mannose in alpha-glucosidase I, and
      glucose in alpha-glucosidase II. 

PMID- 24310139
TI  - Pentose phosphate metabolism during dormancy breakage in Corylus avellana L.
AB  - Commercially obtained fruits of Corylus avellana exhibit the characteristic loss
      of dormancy of this seed following chilling under moist conditions. The
      activities of cytosolic and organellar enzymes of pentose phosphate pathway in
      cotyledonary tissue were assayed throughout stratification and over a similar
      period in damp vermiculite at 20 degrees  C. Glucose-6-phosphate dehydrogenase
      (G6PDH) and 6-phosphogluconic acid dehydrogenase (6PGDH) were both found in
      cytosolic extracts in all treatments; only 6PGDH was present in the organellar
      fraction.The enzyme activities monitored in seeds at 20 degrees  C remained
      relatively constant over the course of the investigation except in the case of
      cytosolic 6PGDH where it is suggested an inhibitor of the enzyme accumulated.
      This inhibitor was removed by the partial purification procedure. Increases in
      the activities of the enzymes occurred during stratification, the major increase
      coinciding exactly with dormancy breakage but prior to the initiation of
      germination. The marked increase in G6PDH and 6PGDH concurrent with the change in
      germination potential of the chilled seed may have considerable biochemical
      significance in breaking down the dormant state. 

PMID- 24310140
TI  - Role of phloem in sucrose transport by Ricinus cotyledons.
AB  - Sucrose is taken up and accumulated by cotyledons of Ricinus communis L.
      Autoradiographic studies reveal a predominant accumulation of sucrose in the
      phloem of the cotyledons. The export of sucrose from the cotyledons to hypocotyl
      and roots proceeds in the phloem by mass flow. These results, taken together with
      previous data, are experimental evidence for proton-sucrose symport as the
      mechanism of phloem loading. 

PMID- 24310141
TI  - The mechanism of deuterium oxide-induced protein degradation in Lemna minor.
AB  - Transfer of Lemna minor fronds to culture medium containing 50% (v/v) deuterium
      oxide induces a large increase in the rate of protein breakdown, which is not due
      to an increase in the activity of acidic or neutral proteolytic enzymes or
      peptidases. Biochemical and ultrastructural evidence indicates that deuterium
      oxide affects the properties of certain membranes, particularly the tonoplast,
      and allows vacuolar proteolytic enzymes to pass into the cytoplasm and cause the
      increased protein breakdown. 

PMID- 24310142
TI  - The effect of plant growth regulator treatments on the levels of ethylene
      emanating from excised turgid and wilted wheat leaves.
AB  - Abscisic acid (ABA) inhibits the production of ethylene induced by water stress
      in excised wheat leaves and counteracts the stimulatory effect of 6-benzyladenine
      (BA) on this process. The stimulatory effect of BA and the inhibitory effect of
      ABA were equally pronounced whether external or endogenous ethylene levels were
      determined. When leaves were sprayed or floated on solutions of BA, indole-3
      acetic acid (IAA), gibberellic acid (GA3), or ABA, the relative activities of
      these growth regulators on stress-induced ethylene at 10(-4) mol l(-1) were
      BA>IAA >GA3>controls>ABA. In non-stressed leaves, however, where the levels of
      ethylene produced were 2-20 times smaller, the relative activities were IAA
      >BA>GA3>controls>ABA. The effects of BA and ABA spray treatment on water stress
      induced ethylene were closely similar whether the solutions were applied 2 or 18
      h prior to the initiation of water stress. The relationships between the levels
      of endogenous growth regulators in the plant and ethylene release induced by
      water stress are discussed. 

PMID- 24310143
TI  - 5-Fluorouracil resistance in carrot cell cultures : Its use in studying the
      interaction of the pyrimidine and arginine pathways.
AB  - Physiological studies of 5-fluorouracil (5-FU)-resistant cell line of wild carrot
      (Daucus carota L.), F5, showed that this variant is also resistant to 5
      fluorouridine, but is as sensitive to 6-azauracil as the 5-FU-sensitive parent
      line, WOO1C. High levels of exogenous uracil, uridine, and thymine are slightly
      toxic to F5, but not to WOO1C. 5-FU sensitivity in WOO1C cannot be reversed by
      bases and nucleosides; bases like uracil and thymine even increase 5-FU toxicity.
      No substantial differences were found in the uptake, incorporation and
      degradation of WOO1C and F5. Carrot cultures seem to take up 5-FU by rapid
      diffusion, the kinetics being characteristic of non-saturable uptake, with
      infinite Km and zero Vmax. The rapid uptake of 5-FU and extensive degradation of
      bases and nucleosides are probably responsible for the inability of uracil and
      uridine to reverse the growth inhibition caused by 5-FU in carrot cells while, as
      shown earlier, phaseolotoxin ((N-phosphosulfamyl)ornithinylalanylhomoarginine),
      an inhibitor of the arginine biosynthetic enzyme, ornithine transcarbamylase was
      capable of reducing 5-FU toxicity. F5 callus contained less histidine and
      arginine than WOO1C. 5-FU increased the endogenous levels of arginine, histidine
      and aspartate in both lines. The aspartate transcarbamylase of F5 appears to be
      normal; it is as sensitive to uridine-monophosphate inhibition as that of WOO1C.
      The 5-FU resistance of F5 was stable in undifferentiated cells, but only 8 out of
      50 calli reinitiated from the regenerated plantlets remained resistant to 5-FU.
      F5 is an aneuploid culture. Five 5-FU-sensitive reinitiated calli that were
      examined were all diploid whereas of the eight 5-FU-resistant reinitiated calli
      two became diploid and six remained as aneuploid. 

PMID- 24310144
TI  - Studies on ethylene binding by cell-free preparations from cotyledons of
      Phaseolus vulgaris L. : I. Separation and characterisation.
AB  - The preparation is described of a cell-free system from developing cotyledons of
      Phaseolus vulgaris cv. Canadian Wonder which is capable of binding ethylene. The
      binding is saturable and the apparent dissociation constant for ethylene is
      6.4.10(-10) M in solution. The binding site is associated with subcellular
      particles and treatment with Triton X-100 results in substantial solubilisation
      of the activity. The kinetics of association and dissociation of the ligand and
      the binding site are described. The system is heat labile and binding activity is
      diminished by treatment with some proteolytic enzymes. 

PMID- 24310145
TI  - Studies on ethylene binding by cell free preparations from cotyledons of
      Phaseolus vulgaris L. : II. Effects of structural analogues of ethylene and of
      inhibitors.
AB  - Various protein reactive agents such as dithioerythritol, dithiothreitol,
      mercaptoethanol and p-chloromercuribenzoate inhibit binding of ethylene to cell
      free preparations of Phaseolus vulgaris L. The effect of the thiols is partially
      reversed by treatment with diamide; occupation of the binding site by ligand
      diminishes the inhibition caused by p-chloromercuribenzoate but not that caused
      by thiols. Growth regulators other than ethylene do not affect binding.
      Physiologically active structural analogues of ethylene competitively inhibit
      binding of the growth regulator and their relative effectiveness in the cell free
      system closely resembles that in developmental processes controlled ethylene. 

PMID- 24310146
TI  - Primer dependent and independent forms of soluble starch synthetase from
      developing barley endosperms.
AB  - The activity of soluble starch synthetase (ADP-glucose: alpha-1,4-glucan alpha-4
      glucosyltransferase) in the non-purified extract from 16 day-old Bomi barley
      endosperms (Hordeum vulgare L.) was low and the reaction was non-linear when
      plotted against protein concentration. Starch synthetase was purified by ammonium
      sulfate precipitation and DEAE-cellulose chromatography and separated into four
      fractions. In the absence of an added carbohydrate primer two of the four
      fractions catalized the synthesis of a methanol-precipitable alpha-glucan when
      high concentrations of sodium citrate and bovine serum albumim were added. The
      rate of alpha-glucan synthesis by the unprimed reaction was higher than for the
      primed reaction. The four enzyme fractions were active with ADP-Glc, but not with
      UDP-Glc, both in the primed and in the unprimed reaction. 

PMID- 24310147
TI  - Molecular pathology and genetics of gastrointestinal neuroendocrine tumours.
AB  - PURPOSE OF REVIEW: Neuroendocrine tumours (NETs) of the luminal gastrointestinal
      tract and pancreas are increasing in incidence and prevalence. Prior assumptions
      about the benign nature of 'carcinoids' and the clinical importance of
      distinguishing functional vs. nonfunctional tumours are being overturned through
      greater understanding of disease behaviour and heterogeneity. This review
      highlights the most contemporary genetic and molecular insights into
      gastroenteropancreatic NETs. RECENT FINDINGS: Biomarkers such as neuron-specific
      enolase or chromogranin A could be supplemented or supplanted by PCR-based
      analysis of NET genes detectable in the blood transcriptome. Conventional
      pathology, including Ki67 testing, could be enhanced with immunohistochemistry
      and exome analysis. Prognostic markers and/or putative therapeutic targets
      uncovered through recent studies include heparanase, Id, ATM, SRC, EGFR, hsp90
      and PDGFR. SUMMARY: After a long-standing paucity of options for conventional
      cytotoxic therapy, the comprehension and treatment of gastroenteropancreatic NETs
      has been enriched by advancements in taxonomy, molecular pathology and
      genetic/epigenetic testing. VIDEO ABSTRACT: 

PMID- 24310148
TI  - Proton pump inhibitor therapy and potential long-term harm.
AB  - PURPOSE OF REVIEW: This review summarizes the recent literature on the potential
      side-effects of proton pump inhibitors (PPIs) and known interactions with the
      metabolism/absorption of other drugs. RECENT FINDINGS: Data confirm that PPIs are
      a very well tolerated drug class. Their high safety, efficacy and wide
      distribution lead to overuse, inappropriate dosage or excessive duration of
      treatment. Despite the absorption of micronutrients or other plausible effects on
      the development of bacterial infections linked to PPI-induced hypochlorhydria, it
      is difficult to demonstrate an association between PPI and specific symptoms. A
      possible negative effect of PPIs on bone integrity appears weak, but
      hypomagnesemia is likely a PPI drug class effect. A higher risk of Clostridium
      difficile infection and other infectious diseases such as small intestinal
      bacterial overgrowth and spontaneous bacterial peritonitis remain controversial
      in PPI users. However, the careful use of PPIs in cirrhotic or otherwise fragile
      patients is mandatory. Short-term or long-term PPI use may trigger microscopic
      colitis, and the management of this condition may include PPI withdrawal. The
      effect of PPIs on stimulating exocrine or endocrine gastric cell proliferation is
      poorly understood. A diagnostic delay or masking of diseases such as gastrinoma
      is difficult to evaluate. SUMMARY: Short-term standard dose PPI treatment is low
      risk. Long-term PPI use may complicate health conditions by various mechanisms
      linked to PPIs and/or to hypochlorhydria.

PMID- 24310149
TI  - Eye care use among a high-risk diabetic population seen in a public hospital's
      clinics.
AB  - IMPORTANCE: Little is known regarding eye care use among low-income persons with
      diabetes mellitus, especially African Americans. OBJECTIVE: To investigate eye
      care use among patients with diabetes who were seen in a county hospital clinic
      that primarily serves high-risk, low-income, non-Hispanic African American
      patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study with 2
      years of follow-up examined eye care use among adult patients with diabetes seen
      in 2007 in an outpatient medical clinic of a large, urban county hospital that
      primarily serves low-income, non-Hispanic African American patients. Patients
      with a history of retinopathy and macular edema or a current diagnosis indicating
      ophthalmic complications were excluded. Eye care use was defined dichotomously as
      whether or not patients had a visit to the eye clinic for any eye care
      examination or procedure. We estimated crude and adjusted rate ratios (aRRs) and
      95% CIs for the association between eye care use and selected clinical and
      demographic characteristics. RESULTS: There were 867 patients with diabetes
      identified: 61.9% were women, 76.2% were non-Hispanic African American, and 61.4%
      were indigent, with a mean age of 51.8 years. Eye care utilization rates were
      33.2% within 1 and 45.0% within 2 years. For patients aged 19 to 39 years
      compared with those aged 65 years or older, significantly decreased eye care
      utilization rates were observed within 1 year (aRR, 0.48; 95% CI, 0.27-0.84) and
      within 2 years (aRR, 0.61; 95% CI, 0.38-0.99). CONCLUSIONS AND RELEVANCE: Overall
      eye care utilization rates were low. Additional education efforts to increase the
      perception of need among urban minority populations may be enhanced if focused on
      younger persons with diabetes.

PMID- 24310151
TI  - Thermoluminescence as a probe of Photosystem II in intact leaves: Non
      photochemical fluorescence quenching in peas grown in an intermittent light
      regime.
AB  - We have measured thermoluminescence (TL) and chlorophyll fluorescence from leaves
      of peas grown under an intermittent light regime (IML) and followed changes in
      those leaves during greening. IML peas show low variable fluorescence and a
      certain capacity for reversible non-photochemical quenching. It has been
      suggested that reversible quenching may be caused by pH-dependent release of
      Ca(2+) from Photosystem II (PS II) (Krieger and Weis (1992) Photosynthetica 27:
      89-98). Under conditions in which reversible non-photochemical quenching occurs,
      a TL band at around 50  degrees C is observed, in the presence of DCMU, in IML
      leaves. A band in this temperature range has previously been observed in PS II
      depleted of Ca(2+) (Ono and Inoue (1989) Biochimica et Biophysica Acta 973: 443
      449). The 50  degrees C band disappears upon dark adaptation. In mature leaves,
      no significant band is seen at 50  degrees C. It is concluded that, in IML
      leaves, reversible quenching may be related to the release of Ca(2+) from
      Photosystem II. However, it seems that in the mature system, under most
      conditions, such release does not contribute significantly to quenching. 

PMID- 24310152
TI  - Reconstitution of iron-sulfur center B of Photosystem I damaged by mercuric
      chloride.
AB  - Incubation of thylakoid membranes from spinach with low concentrations of
      mercuric chloride induces the loss of one of the iron-sulfur centers, FB, in
      Photosystem I (PS I) and inhibits the electron transfer from PS I to the soluble
      electron carrier, ferredoxin. Reconstitution of this damaged iron-sulfur center
      has been carried out by incubating treated thylakoid membranes with exogenous
      FeCl3 and Na2S in the presence ofbeta-mercaptoethanol under anaerobic conditions.
      Low temperature EPR measurements indicate that center FB is largely restored.
      Kinetic experiments show that the restored FB can be photoreduced from P700.
      However, these reconstituted thylakoid membranes are still incompetent in the
      photoreduction of ferredoxin and NADP(+), even though ferredoxin binding to the
      modified membranes was not impaired, indicating additional changes in the
      structure of the PS I complex must have occurred. 

PMID- 24310150
TI  - Social transmission of Pavlovian fear: fear-conditioning by-proxy in related
      female rats.
AB  - Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an
      aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative
      learning such that the tone alone will elicit a conditioned response (e.g.,
      freezing). Individuals can also acquire fear from a social context, such as
      through observing the fear expression of a conspecific. In the current study, we
      examined the influence of kinship/familiarity on social transmission of fear in
      female rats. Rats were housed in triads with either sisters or non-related
      females. One rat from each cage was fear conditioned to a tone CS+ shock US. On
      day two, the conditioned rat was returned to the chamber accompanied by one of
      her cage mates. Both rats were allowed to behave freely, while the tone was
      played in the absence of the foot-shock. The previously untrained rat is referred
      to as the fear-conditioned by-proxy (FCbP) animal, as she would freeze based on
      observations of her cage-mate's response rather than due to direct personal
      experience with the foot-shock. The third rat served as a cage-mate control. The
      third day, long-term memory tests to the CS were performed. Consistent with our
      previous application of this paradigm in male rats (Bruchey et al. in Behav Brain
      Res 214(1):80-84, 2010), our results revealed that social interactions between
      the fear conditioned and FCbP rats on day two contribute to freezing displayed by
      the FCbP rats on day three. In this experiment, prosocial behavior occurring at
      the termination of the cue on day two was significantly greater between sisters
      than their non-sister counterparts, and this behavior resulted in increased
      freezing on day three. Our results suggest that familiarity and/or kinship
      influences the social transmission of fear in female rats.

PMID- 24310153
TI  - Photophysics of the carotenoids associated with the xanthophyll cycle in
      photosynthesis.
AB  - Green plants use the xanthophyll cycle to regulate the flow of energy to
      chlorophylla within photosynthetic proteins. Under conditions of low light
      intensity violaxanthin, a carotenoid possessing nine conjugated double bonds,
      functions as an antenna pigment by transferring energy from its lowest excited
      singlet state to that of chlorophylla within light-harvesting proteins. When the
      light intensity increases, violaxanthin is biochemically transformed into
      zeaxanthin, a carotenoid that possesses eleven conjugated double bonds. The
      results presented here show that extension of the [Symbol: see text] conjugation
      of the polyene lowers the energy of the lowest excited singlet state of the
      carotenoid below that of chlorophylla. As a consequence zeaxanthin can act as a
      trap for the excess excitation energy on chlorophylla pigments within the
      protein, thus regulating the flow of energy within photosynthetic light
      harvesting proteins. 

PMID- 24310154
TI  - Measurements of mesophyll conductance, photosynthetic electron transport and
      alternative electron sinks of field grown wheat leaves.
AB  - Photosynthetic electron transport drives the carbon reduction cycle, the carbon
      oxidation cycle, and any alternative electron sinks such as nitrogen reduction. A
      chlorophyll fluorescence- based method allows estimation of the total electron
      transport rate while a gas-exchange-based method can provide estimates of the
      electron transport needed for the carbon reduction cycle and, if the CO2 partial
      pressure inside the chloroplast is accurately known, for the carbon oxidation
      cycle. The gas-exchange method cannot provide estimates of alternative electron
      sinks. Photosynthetic electron transport in flag leaves of wheat was estimated by
      the fluorescence method and gasexchange method to determine the possible
      magnitude of alternative electron sinks. Under non-photorespiratory conditions
      the two measures of electron transport were the same, ruling out substantial
      alternative electron sinks. Under photorespiratory conditions the fluorescence
      based electron transport rate could be accounted for by the carbon reduction and
      carbon oxidation cycle only if we assumed the CO2 partial pressure inside the
      chloroplasts to be lower than that in the intercellular spaces of the leaves. To
      further test for the presence of alternative electron sinks, carbon metabolism
      was inhibited by feeding glyceraldehyde. As carbon metabolism was inhibited, the
      electron transport was inhibited to the same degree. A small residual rate of
      electron transport was measured when carbon metabolism was completely inhibited
      which we take to be the maximum capacity of alternative electron sinks. Since the
      alternative sinks were small enough to ignore, the comparison of fluorescence and
      gas-exchange based methods for measuring the rate of electron transport could be
      used to estimate the mesophyll conductance to CO2 diffusion. The mesophyll
      conductance estimated this way fell as wheat flag leaves senesced. The age
      related decline in photosynthesis may be attributed in part to the reduction of
      mesophyll conductance to CO2 diffusion and in part to the estimated decline of
      ribulose 1,5-bisphosphate carboxylase amount. 

PMID- 24310155
TI  - Comparison of the photoreduction of protochlorophyllide to chlorophyllide in
      leaves and cotyledons from dark-grown bean as a function of age.
AB  - 77 K fluorescence spectra of bean (Phaseolus vulgaris cv Commodore) leaves and
      cotyledons show the presence of active and inactive protochlorophyllides. The
      first detected product of the protochlorophyllide photoreduction is the
      chlorophyllide emitting fluorescence at 690 nm (C690) which is observed one day
      (leaves) and three days (cotyledons) after sowing. In cotyledons, C690 undergoes
      the 'rapid' and 'Shibata' shifts; in leaves, these spectral changes are age
      dependent. In order to characterize the formation of C690, we have recorded 298 K
      fluorescence kinetics at 690 nm and the corresponding absorbance kinetics at 440
      nm. The amplitude of the variations of both kinetics increases with the sample
      age. The absorbance and fluorescence kinetics can be modelized as a
      monoexponential law. The rate constant of the absorbance and fluorescence
      kinetics does not significantly change during the studied period (except for old
      cotyledons). The results presented in this paper give evidences for a low energy
      transfer between pigments during the photoreduction of protochlorophyllide at
      room temperature. 

PMID- 24310156
TI  - Rates of vectorial proton transport supported by cyclic electron flow during
      oxygen reduction by illuminated intact chloroplasts.
AB  - The light-dependent quenching of 9-aminoacridine fluorescence was used to monitor
      the state of the transthylakoid proton gradient in illuminated intact
      chloroplasts in the presence or absence of external electron acceptors. The
      absence of appreciable light-dependent fluorescence quenching under anaerobic
      conditions indicated inhibition of coupled electron transport in the absence of
      external electron acceptors. Oxygen relieved this inhibition. However, when DCMU
      inhibited excessive reduction of the plastoquinone pool in the absence of oxygen,
      coupled cyclic electron transport supported the formation of a transthylakoid
      proton gradient even under anaerobiosis. This proton gradient collapsed in the
      presence of oxygen. Under aerobic conditions, and when KCN inhibited ribulose
      bisphosphate carboxylase and ascorbate peroxidase, fluorescence quenching
      indicated the formation of a transthylakoid proton gradient which was larger with
      oxygen in the Mehler reaction as electron acceptor than with methylviologen at
      similar rates of linear electron transport. Apparently, cyclic electron transport
      occured simultaneously with linear electron transport, when oxygen was available
      as electron acceptor, but not when methylviologen accepted electrons from
      Photosystem I. The ratio of cyclic to linear electron transport could be
      increased by low concentrations of DCMU. This shows that even under aerobic
      conditions cyclic electron transport is limited in isolated intact chloroplasts
      by excessive reduction of electron carriers. In fact, P700 in the reaction center
      of Photosystem I remained reduced in illuminated isolated chloroplasts under
      conditions which resulted in extensive oxidation of P700 in leaves. This shows
      that regulation of Photosystem II activity is less effective in isolated
      chloroplasts than in leaves. Assuming that a Q-cycle supports a H(+)/e ratio of 3
      during slow linear electron transport, vectorial proton transport coupled to
      Photosystem I-dependent cyclic electron flow could be calculated. The highest
      calculated rate of Photosystem I-dependent proton transport, which was not yet
      light-saturated, was 330 MUmol protons (mg chlorophyll h)(-1) in intact
      chloroplasts. If H(+)/e is not three but two proton transfer is not 330 but 220
      MUmol (mg Chl H)(-1). Differences in the regulation of cyclic electron transport
      in isolated chloroplasts and in leaves are discussed. 

PMID- 24310157
TI  - An active Mehler-peroxidase reaction sequence can prevent cyclic PS I electron
      transport in the presence of dioxygen in intact spinach chloroplasts.
AB  - Simultaneous measurements of 9-aminoacridine (9-AA) fluorescence quenching, O2
      uptake and chlorophyll fluorescence of intact spinach chloroplasts were carried
      out to assess the relationship between the transthylakoidal DeltapH and linear
      electron flux passing through Photosystem II. Three different types of O2
      dependent electron flow were investigated: (1) Catalysed by methyl viologen; (2)
      in the absence of a catalyst and presence of an active ascorbate peroxidase
      (Mehler-peroxidase reaction); (3) in the absence of a catalyst and with the
      ascorbate peroxidase being inhibited by KCN (Mehler reaction). The aim of this
      study was to assess the relative contribution of DeltapH-formation which is not
      associated with electron flow through Photosystem II and, which should reflect
      Photosystem I cyclic flow under the different conditions. The relationship
      between the extent of 9-AA fluorescence quenching and O2-uptake rate was found to
      be almost linear when methyl viologen was present. In the absence of methyl
      viologen (Mehler reaction) an increase of 9-AA fluorescence quenching to a value
      of 20% at low light intensities was associated with considerably less O2-uptake
      than in the presence of methyl viologen, indicating the involvement of cyclic
      flow. These findings are in agreement with a preceding study of Kobayashi and
      Heber (1994). However, when no KCN was added, such that the complete Mehler
      peroxidase reaction sequence was operative, the relationship between 9-AA
      fluorescence quenching and the flux through PS II, as measured via the
      chlorophyll fluorescence parameter DeltaF/Fm' * PAR, was identical to that
      observed in the presence of methyl viologen. Under the assumption that methyl
      viologen prevents cyclic flow, it is concluded that there is no significant
      contribution of cyclic electron flow to DeltapH-generation in intact spinach
      chloroplasts. 

PMID- 24310158
TI  - Mathematical modelling of photoinhibition and Photosystem II repair cycle. I.
      Photoinhibition and D1 protein degradation in vitro and in the absence of
      chloroplast protein synthesis in vivo.
AB  - The kinetics of photoinhibition of Photosystem II and D1 protein degradation were
      studied by applying mathematical modelling to new and published data. The word
      'photoinhibition' refers here only to such inhibition of PS II activity that
      requires chloroplast protein synthesis for recovery. It is shown that acceptor
      side photoinhibition in vitro as well as in vivo photoinhibition in higher plants
      and cyanobacteria in the presence of prokaryotic translation inhibitors follow
      first-order kinetics. Degradation of damaged D1 protein also fits in a first
      order reaction equation with respect to the concentration of photoinhibited PS II
      centres. It is shown that photoprotective lowering of the ratio of variable to
      maximum fluorescence can be distinguished from the lowering of this ratio
      associated with photoinhibition. 

PMID- 24310159
TI  - Xanthophyll cycle components and capacity for non-radiative energy dissipation in
      sun and shade leaves ofLigustrum ovalifolium exposed to conditions limiting
      photosynthesis.
AB  - The relationships between photosynthetic efficiency, non-radiative energy
      dissipation and carotenoid composition were studied in leaves ofLigustrum
      ovalifolium developed either under full sunlight or in the shade. Sun leaves
      contained a much greater pool of xanthophyll cycle components than shade leaves.
      The rate of non-radiative energy dissipation, measured as non-photochemical
      fluorescence quenching (NPQ), was strictly related to the deepoxidation state
      (DPS) of xanthophyll cycle components in both sun and shade leaves, indicating
      that zeaxanthin (Z) and antheraxanthin (A) are involved in the development of
      NPQ. Under extreme conditions of excessive energy, sun leaves showed higher
      maximum DPS than shade leaves. Therefore, sun leaves contained not only a greater
      pool of xanthophyll cycle components but also a higher proportion of violaxanthin
      (V) actually photoconvertible to A and Z, compared to shade leaves. Both these
      effects contributed to the higher NPQ in sun versus shade leaves. The amount of
      photoconvertible V was strongly related to chla/b ratio and inversely to leaf
      neoxanthin content. This evidence indicates that the amount of photoconvertible V
      may be dependent on the degree of thylakoid membrane appression and on the
      organization of chlorophyll-protein complexes, and possible explanations are
      discussed. Exposure to chilling temperatures caused a strong decline in the
      photon yield of photosynthesis and in the intrinsic efficiency of PS II
      photochemistry in sun leaves, but little effects in shade leaves. These effects
      were accompanied by increases in the pool of xanthophyll cycle components and in
      DPS, more pronounced in sun than in shade leaves. This corroborates the view that
      Z and A may play a photoprotective role under unfavorable conditions. In addition
      to the xanthophyll-related non-radiative energy dissipation, a slow relaxing
      component of NPQ, independent from A and Z concentrations, has been found in
      leaves exposed to low temperature and high light. This quenching component may be
      attributed either to other regulatory mechanism of PS II efficiency or to
      photoinactivation. 

PMID- 24310160
TI  - Gaussian band analysis of absorption, fluorescence and photobleaching difference
      spectra of D1/D2/cytb-559 complex.
AB  - A study of the absorption and fluorescence characteristics of the D1/D2/cytb-559
      reaction centre complex of Photosystem II has been carried out by gaussian
      decomposition of absorption spectra both at room temperature and 72 K and of the
      room temperature fluorescence spectrum. A five component fit was found in which
      the absorption and fluorescence sub-bands could be connected by the Stepanov
      relation. The photobleaching and light-activated degradation in the dark of long
      wavelength pigments permitted a further characterisation of the absorption bands.
      The absorption (fluorescence) maxima of the five bands at room temperature are
      660 nm (670 nm), 669 nm (675 nm), 675 nm (681 nm), 680 nm (683 nm), 681 nm (689
      nm). A novel feature of this analysis is the presence of two approximately
      isoenergetic absorption bands near 680 nm at room temperature. The narrower one
      (FWHM=12.5 nm) is attributed to pheophytin while the broader band (FWHM=23 nm) is
      thought to be P680. The P680 band width is discussed in terms of homogeneous and
      site inhomogeous band broadening. The P680 fluorescence has a large Stokes shift
      (~9 nm) and most fluorescence in the 690-700 nm range is associated with this
      chromophore.The three accessory pigment bands are broad (FWHM=17-24 nm) and the
      660 nm gaussian is largely temperature insensitive thus indicating significant
      site inhomogeneous broadening.The very slight narrowing of the D1/D2/cytb-559 Qy
      absorption at crytogenic temperatures is discussed in terms of the coarse
      spectral inhomogeneity associated with the spectral forms and the apparently
      large site inhomogeneous broadening of short wavelength accessory pigments. 

PMID- 24310161
TI  - Two dimensional electrophoresis of thylakoid membrane proteins and its
      application to microsequencing.
AB  - A procedure of two-dimensional gel electrophoresis adapted for application on
      membrane proteins from the thylakoids is described. It involves isoelectric
      focusing in the first dimension and size dependent electrophoresis in the second
      dimension. About 100 polypeptides are clearly separated with relatively little
      streaking. About 20 polypeptides are identified by immunoblotting or location in
      the gel. They are the polypeptides of the PS I core, the 64 kDa protein, the
      alpha and beta subunits of CF1 ATPase, cytochrome f, Rieske iron-sulfur protein,
      the 23 kDa and 33 kDa polypeptides of the oxygen evolving complexes, CP29, CP24,
      CP27 and CP25 (last two proteins belong to LHCII). Some proteins give rise to two
      or more separate spots indicating a separation of different isoforms of these
      proteins. Among them, the LHCII polypeptides (27 kDa and 25 kDa) were each
      resolved into at least three spots in the pH range 4.75-5.90; the Rieske FeS
      protein, as published elsewhere (Yu et al. 1994), was separated into two forms
      having different isoelectric points (pI 5.1 and 5.4), each of them was also
      microsequenced; the 64 kDa protein claimed to be a LHCII-kinase was found to be
      multiple forms appearing in at least two isoforms with pI 6.2 (K1) and 6.0 (K2)
      respectively, furthermore, K1 can be resolved into two subpopulations.The lateral
      distribution of these proteins in the thylakoid membrane was determined by
      analysing the vesicles originating from different parts of the thylakoids. The
      data obtained from this analysis can be partially used as markers for different
      thylakoid domains.This procedure for sample solubilization and 2-D
      electrophoresis is useful for the analysis of the polypeptide composition of
      vesicles originating from the thylakoid membrane and for microsequences of
      individual polypeptides isolated from the 2-D gel. 

PMID- 24310162
TI  - Comparing no-flow time during endotracheal intubation versus placement of a
      laryngeal mask airway during a simulated cardiac arrest scenario.
AB  - INTRODUCTION: Traditionally, pausing chest compressions during airway management
      in a cardiac arrest has been the accepted norm. However, updated American Heart
      Association and the European Resuscitation Council guidelines for Advanced
      Cardiac Life Support emphasize reducing pauses in chest compressions, often
      referred to as "no-flow time," to improve return of spontaneous circulation. We
      used simulation to evaluate whether placing a laryngeal mask airway versus
      endotracheal intubation via direct laryngoscopy would reduce no-flow times during
      a simulated cardiac arrest. METHODS: A crossover trial of 41 respiratory
      therapists (RTs) performed airway management in a simulated cardiac arrest. The
      RTs were told that bag mask ventilation was inadequate, and either an
      endotracheal tube or laryngeal mask airway was needed. They were informed to
      request the cessation of chest compressions only if needed to complete the airway
      maneuver. The study was terminated when ventilation was achieved. The scenario
      was repeated with the same RT placing the alternative airway. Insertion time and
      no-flow times were recorded. RESULTS: Neither endotracheal intubation via direct
      laryngoscopy nor laryngeal mask airway placement increased no-flow time. Only 1
      participant requested cessation of chest compressions during direct laryngoscopy
      for 2.3 seconds (P = 0.175). However, ventilation was established significantly
      faster with a laryngeal mask airway compared with endotracheal intubation (49.2
      vs. 31.6 seconds, respectively, P < 0.001). CONCLUSIONS: We conclude that
      although neither device was superior to the other with respect to the primary
      outcome of reducing no-flow time, effective ventilation was established more
      rapidly with the laryngeal mask airway in the hands of the RTs who participated
      in this study. These results may be affected by the differences between simulated
      and human airways.

PMID- 24310163
TI  - A mixed-reality part-task trainer for subclavian venous access.
AB  - INTRODUCTION: Mixed-reality (MR) procedural simulators combine virtual and
      physical components and visualization software that can be used for debriefing
      and offer an alternative to learn subclavian central venous access (SCVA). We
      present a SCVA MR simulator, a part-task trainer, which can assist in the
      training of medical personnel. METHODS: Sixty-five participants were involved in
      the following: (1) a simulation trial 1; (2) a teaching intervention followed by
      trial 2 (with the simulator's visualization software); and (3) trial 3, a final
      simulation assessment. The main test parameters were time to complete SCVA and
      the SCVA score, a composite of efficiency and safety metrics generated by the
      simulator's scoring algorithm. Residents and faculty completed questionnaires
      presimulation and postsimulation that assessed their confidence in obtaining
      access and learner satisfaction questions, for example, realism of the simulator.
      RESULTS: The average SCVA score was improved by 24.5 (n=65). Repeated-measures
      analysis of variance showed significant reductions in average time (F=31.94,
      P<0.0001), number of attempts (F=10.56, P<0.0001), and score (F=18.59, P<0.0001).
      After the teaching intervention and practice with the MR simulator, the results
      no longer showed a difference in performance between the faculty and residents.
      On a 5-point scale (5=strongly agree), participants agreed that the SCVA
      simulator was realistic (M=4.3) and strongly agreed that it should be used as an
      educational tool (M=4.9). CONCLUSIONS: An SCVA mixed simulator offers a realistic
      representation of subclavian central venous access and offers new debriefing
      capabilities.

PMID- 24310164
TI  - Measuring sense of presence and user characteristics to predict effective
      training in an online simulated virtual environment.
AB  - INTRODUCTION: Virtual-reality solutions have successfully been used to train
      distributed teams. This study aimed to investigate the correlation between user
      characteristics and sense of presence in an online virtual-reality environment
      where distributed teams are trained. A greater sense of presence has the
      potential to make training in the virtual environment more effective, leading to
      the formation of teams that perform better in a real environment. Being able to
      identify, before starting online training, those user characteristics that are
      predictors of a greater sense of presence can lead to the selection of trainees
      who would benefit most from the online simulated training. METHODS: This is an
      observational study with a retrospective postsurvey of participants' user
      characteristics and degree of sense of presence. Twenty-nine members from 3 Air
      Force National Guard Medical Service expeditionary medical support teams
      participated in an online virtual environment training exercise and completed the
      Independent Television Commission-Sense of Presence Inventory survey, which
      measures sense of presence and user characteristics. Nonparametric statistics
      were applied to determine the statistical significance of user characteristics to
      sense of presence. RESULTS: Comparing user characteristics to the 4 scales of the
      Independent Television Commission-Sense of Presence Inventory using Kendall tau
      test gave the following results: the user characteristics "how often you play
      video games" (tau(26)=-0.458, P<0.01) and "television/film production knowledge"
      (tau(27)=-0.516, P<0.01) were significantly related to negative effects. Negative
      effects refer to adverse physiologic reactions owing to the virtual environment
      experience such as dizziness, nausea, headache, and eyestrain. The user
      characteristic "knowledge of virtual reality" was significantly related to
      engagement (tau(26)=0.463, P<0.01) and negative effects (tau(26)=-0.404, P<0.05).
      CONCLUSIONS: Individuals who have knowledge about virtual environments and
      experience with gaming environments report a higher sense of presence that
      indicates that they will likely benefit more from online virtual training. Future
      research studies could include a larger population of expeditionary medical
      support, and the results obtained could be used to create a model that predicts
      the level of presence based on the user characteristics. To maximize results and
      minimize costs, only those individuals who, based on their characteristics, are
      supposed to have a higher sense of presence and less negative effects could be
      selected for online simulated virtual environment training.

PMID- 24310165
TI  - Development of a haptic model for teaching in reconstructive surgery--the radial
      forearm flap.
AB  - OBJECTIVES: The great value of the radial forearm flap (RFF) for reconstructive
      surgery stresses the importance of developing effective teaching methods. Our aim
      was to develop a realistic anatomic model that concisely simulates vital surgical
      steps while offering a haptic and visual experience. It should be cost-effective,
      easy to use, reusable, and quick to set up. MATERIALS AND METHODS: The
      development commenced by constructing a prototype presenting basic features.
      Together with photographic surgery documentation, it served as a blueprint for
      the advanced model. The flap-raising process was condensed into the 6 most
      important steps to illustrate the procedure concisely and chronologically.
      RESULTS: Our final version consists of polyurethane, and a customized forearm
      flexor muscle model serves as the basic structure. Diverse plasticizers give
      different degrees of hardness to mimic anatomic structures. Special didactic
      features of the model include a movable elastic ramus superficialis nervi
      radialis. The flap island is attachable/detachable by a patrix/matrix mechanism.
      The brachioradialis muscle is elastic and detachable, and the fascia antebrachii
      is additionally severable. Vessels can be disconnected, and the removable forearm
      skin features a wave-shaped incision for the flap pedicle. To investigate the
      didactic benefit of the RFF model, we used it in a teaching course for medical
      students. The group receiving teaching supported by the RFF model showed a
      statistically significant improvement of knowledge (P = 0.007) in comparison with
      the group solely receiving a standard lecture supported by surgery images.
      CONCLUSIONS: In our opinion, the RFF model is an excellent compromise with regard
      to realism, didactic benefit, and cost-/time-effectiveness and has proven
      successful in the teaching of medical students.

PMID- 24310167
TI  - A near-infrared fluorescent probe for selective detection of HClO based on Se
      sensitized aggregation of heptamethine cyanine dye.
AB  - A Se-containing heptamethine cyanine dye based fluorescent probe was successfully
      developed and used for HClO detection with rapid response and high selectivity
      based on aggregation behavior. The probe could react with HClO with significant
      change in its fluorescence profile, which makes it practical for detecting HClO
      in fetal bovine serum and in living mice. 

PMID- 24310166
TI  - Mgat2 ablation in the myeloid lineage leads to defective glycoantigen T cell
      responses.
AB  - N-linked glycosylation is a central regulatory factor that influences the immune
      system in varied and profound ways, including leukocyte homing, T cell receptor
      signaling and others. Moreover, N-glycan branching has been demonstrated to
      change as a function of infection and inflammation. Our previous findings suggest
      that complex-type N-glycans on the class II major histocompatibility complex play
      an important role in antigen selection within antigen presenting cells (APCs)
      such that highly branched N-glycans promote polysaccharide (glycoantigen, GlyAg)
      presentation following Toll-like receptor 2 (TLR2)-dependent antigen processing.
      In order to explore the impact of N-glycan branching on the myeloid-derived APC
      population without the confounding problems of altering the branching of
      lymphocytes and non-hematopoietic cells, we created a novel myeloid-specific
      knockout of the beta-1,2-N-acetylglucosaminyltransferase II (Mgat2) enzyme. Using
      this novel mouse, we found that the reduction in multi-antennary N-glycans
      characteristic of Mgat2 ablation had no impact on GlyAg-mediated TLR2 signaling.
      Likewise, no deficits in antigen uptake or cellular homing to lymph nodes were
      found. However, we discovered that Mgat2 ablation prevented GlyAg presentation
      and T cell activation in vitro and in vivo without apparent alterations in
      protein antigen response or myeloid-mediated protection from infection. These
      findings demonstrate that GlyAg presentation can be regulated by the N-glycan
      branching pattern of APCs, thereby establishing an in vivo model where the T cell
      dependent activity of GlyAgs can be experimentally distinguished from GlyAg
      mediated stimulation of the innate response through TLR2. 

PMID- 24310168
TI  - Global microcirculatory impairment in Takotsubo syndrome: is it present at the
      onset of illness, or it develops later?

PMID- 24310169
TI  - Non-physician-assisted suicide in The Netherlands: a cross-sectional survey among
      the general public.
AB  - CONTEXT: In The Netherlands, approximately 45% of patients' requests for
      euthanasia are granted by a physician. After a rejected request, some patients
      approach non-physicians and ask them for assistance in suicide. Recently, a non
      physician who assisted his mother's suicide was declared guilty without
      punishment. AIM: The aim of the current study was to investigate the opinion of
      the Dutch general public on non-physician-assisted suicide. METHODS: A cross
      sectional survey among the Dutch general public was performed. A total of 1113
      respondents were included (response rate 80%). The survey covered two case
      descriptions in which a patient asks a non-physician for assisted suicide after a
      non-granted request for physician-assisted dying. In both cases, a son, friend or
      professional facilitates the suicide by either the provision of information or
      the purchase of lethal medication. Respondents were invited to give their opinion
      on these cases and in addition on 10 propositions on non-physician-assisted
      suicide. RESULTS: When a son provides information on how to acquire lethal
      medication in case of a patient with a terminal illness, this involvement is
      accepted by 62% of the respondents. The actual purchase of lethal medication
      receives less support (38%). If the patient suffers without a serious disease,
      both forms of assistance are less accepted (46% and 24%, respectively). In
      addition, only 21% support the legalisation of non-physician-assisted suicide.
      The Dutch public prefer involvement of a physician in assisted suicide (69%).
      CONCLUSIONS: The Dutch general public consider non-physician-assisted suicide in
      some specific cases a tolerable alternative for patients with a rejected request
      for physician-assisted dying if the assistance is limited to the provision of
      information. However, the majority do not support the legalisation of non
      physician-assisted suicide.

PMID- 24310170
TI  - Publish or be damned: Individual Funding Requests and the publicity condition.
AB  - Many jurisdictions have processes to consider Individual Funding Requests but,
      with few exceptions, the decisions made with respect to these are not made
      public. Drawing upon Daniels and Sabin's account of the requirements of
      procedural justice, Accountability for Reasonableness, this paper considers
      several arguments for and against publishing individual funding request
      decisions. After briefly reviewing the case for publicity as a requirement of
      procedural justice and canvassing several arguments against publicity, we
      consider whether patient confidentiality justifies suppressing funding decisions.
      We claim that, with one possible exception, publication of individual funding
      request decisions does not raise concerns that are different in kind from those
      that apply to publication of legal judgments relating to healthcare, and that the
      protections instituted in that setting should be sufficient to allow publication
      of funding decisions. The discussion concludes with several cautionary notes. 

PMID- 24310171
TI  - Health research and systems' governance are at risk: should the right to data
      protection override health?
AB  - The European Union (EU) Data Protection Regulation will have profound
      implications for public health, health services research and statistics in
      Europe. The EU Commission's Proposal was a breakthrough in balancing privacy
      rights and rights to health and healthcare. The European Parliament, however, has
      proposed extensive amendments. This paper reviews the amendments proposed by the
      European Parliament Committee on Civil Liberties, Justice and Home Affairs and
      their implications for health research and statistics. The amendments eliminate
      most innovations brought by the Proposal. Notably, derogation to the general
      prohibition of processing sensitive data shall be allowed for public interests
      such as the management of healthcare services,but not health research,
      monitoring, surveillance and governance. The processing of personal health data
      for historical, statistical or scientific purposes shall be allowed only with the
      consent of the data subject or if the processing serves an exceptionally high
      public interest, cannot be performed otherwise and is legally authorised.
      Research, be it academic, government,corporate or market research, falls under
      the same rule.The proposed amendments will make difficult or render impossible
      research and statistics involving the linkage and analysis of the wealth of data
      from clinical,administrative, insurance and survey sources, which have
      contributed to improving health outcomes and health systems performance and
      governance; and may illegitimise efforts that have been made in some European
      countries to enable privacy-respectful data use for research and statistical
      purposes. If the amendments stand as written, the right to privacy is likely to
      override the right to health and healthcare in Europe.

PMID- 24310173
TI  - Late adolescents' conceptualizations of home-leaving.
AB  - Separation from the family, a key developmental task, has received scant
      attention from developmentalists. In this study, college students' dissimilarity
      ratings and ratings on 22 bipolar adjective scales were obtained for a set of 20
      definitions of home-leaving. Results of a cluster analysis revealed that
      conceptualizations of the definitions are organized in terms of eight clusters.
      Ratings on the 22 adjective scales provided an empirical means for interpreting
      the typological structure of the home-leaving definitions. Convergence the
      results of this inductive study of home-leaving and elements of ego development
      theory was noted. 

PMID- 24310174
TI  - Transitions in relationship style from adolescence to young adulthood.
AB  - Literature on friendships of adolescents and young adults suggests important
      gender and age-related differences. In a study of transitions in relationship
      style from middle adolescence (high school) to late adolescence (college), 300
      students described their relationship with the person who was closest to them,
      either same or other sex. Four relationship styles were characteristic:
      integrated (high friendly and high intimate), intimate (high intimate and low
      friendly), friendly (high friendly and low intimate), and uninvolved (low
      intimate and low friendly). Women's more intimate styles of relating, as compared
      to men's more uninvolved styles, suggested that women developed earlier
      competence at intimate relating than did men. Viewed as particularly important
      were the college women's close friendships with those of the same gender, an
      experience uncharacteristic of adolescent men in high school and college. Results
      were discussed in terms of Erikson's stages of development and Sullivan's concept
      of the chum. 

PMID- 24310172
TI  - Recognition of lipopolysaccharide pattern by TLR4 complexes.
AB  - Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram
      negative bacteria. Minute amounts of LPS released from infecting pathogens can
      initiate potent innate immune responses that prime the immune system against
      further infection. However, when the LPS response is not properly controlled it
      can lead to fatal septic shock syndrome. The common structural pattern of LPS in
      diverse bacterial species is recognized by a cascade of LPS receptors and
      accessory proteins, LPS binding protein (LBP), CD14 and the Toll-like receptor4
      (TLR4)-MD-2 complex. The structures of these proteins account for how our immune
      system differentiates LPS molecules from structurally similar host molecules.
      They also provide insights useful for discovery of anti-sepsis drugs. In this
      review, we summarize these structures and describe the structural basis of LPS
      recognition by LPS receptors and accessory proteins. 

PMID- 24310175
TI  - Young adults' scores on the defining issues test as a function of a "self" versus
      "other" presentation mode.
AB  - One hundred college students were randomly divided into four groups and were
      administered the standard version (i.e., other-orientation) of the Defining
      Issues Test (DIT) and/or a Modified version (i.e., self-orientation) of the same
      instrument on two separate occasions. Subjects displayed greater amounts of
      principled moral reasoning when responding to the standard (other-orientation)
      rather than the modified (self-orientation) version of the DIT. Also, significant
      test-retest reliability was obtained for the standard, but not the modified,
      version of the DIT. The role of affective factors in the evaluation of moral
      problems involving the self versus hypothetical others was discussed. 

PMID- 24310176
TI  - The relationship between psychosocial maturity and assertiveness in males and
      females.
AB  - The relationship between psychosocial maturity (psychological health) and
      assertiveness was investigated in a sample of United States college males and
      females. Results revealed a moderately high positive relationship between
      psychosocial maturity (PSM) and self-reported assertiveness on the Rathus and
      Galassi scales for both sexes. This relationship was slightly stronger (in terms
      of variance accounted for) for males than females, significant differences being
      obtained for Intimacy on the Rathus scale and PSM and Intimacy on the Galassi
      scale. Multiple regression analyses revealed that the personality components most
      consistently accounting for major portions of the variance in predicting male
      assertiveness scores on both the Rathus Assertiveness Schedule and the College
      Self-Expression Scale were Intimacy and Initiative, while in predicting female
      assertiveness, only Initiative was involved. The findings were related to
      previous research, recent work on the androgyny construct (instrumental vs.
      expressive behaviors), and exhortations for increased cooperation between schools
      of psychotherapy to establish it as a more unified discipline. 

PMID- 24310177
TI  - Demographic correlates of adolescents' helping behavior.
AB  - The helping behavior of 250 sixth-grade children was assessed by four different
      measures and related to several demographic variables. The results indicated that
      (a) more girls were helpful than boys; (b) more children of European-American and
      Israeli origin were helpful than those of Asian - (North) African origin; (c)
      more children having fathers with a high level of education were helpful than
      those having fathers with a low level of education; and (d) more secondborn
      children were helpful than firstborn. These results are explained and their
      importance indicated. 

PMID- 24310178
TI  - Risks entailed in teenage intoxication as perceived by junior and senior high
      school students.
AB  - In a survey of 1269 junior and senior high school students in a Massachusetts
      community, a large majority of the respondents indicated they recognized many
      immediate and long-term risks involved in getting drunk at their age. A
      considerable minority of the sample, however, did not believe that there were
      significant hazards associated with youthful intoxication. Implications of the
      study for educators, counselors, parents, and others concerned about the
      prevalence of teenage drunkenness are explored. 

PMID- 24310179
TI  - The relationship of father absence and antisocial behavior to social egocentrism
      in adolescent mexican american females.
AB  - This study investigated the relationship of family structure (father absence and
      intact) and the level of antisocial behavior (high and low) to social egocentrism
      in adolescent Mexican American females. The results indicated that high
      antisocial females had significantly higher egocentrism scores than low
      antisocial females. No main effect was found for family structure. A significant
      interaction was found between antisocial behavior and family structure,
      indicating that the high antisocial-father absent group had the highest
      egocentrism scores among the four groups. 

PMID- 24310180
TI  - Multimodal chemo-magnetic control of self-propelling microbots.
AB  - We report a controlled migration of an iron nanoparticle (FeNP) coated polymer
      micromotor. The otherwise diffusive motion of the motor was meticulously directed
      through an in situ pH-gradient and an external magnetic field. The self
      propulsion owing to the asymmetric catalytic decomposition of peroxide fuel was
      directed through a pH gradient imposed across the motor-surface, while the
      magnetic field induced an external control on the movement and the speed of the
      motor. Interestingly, the sole influence of the pH gradient could move the motor
      as high as ~25 body lengths per second, which was further magnified by the
      external assistance from the magnetic field. Applying a magnetic field against
      the pH directed motion helped in the quantitative experimental estimation of the
      force-field required to arrest the chemotactic migration. The influence of the
      coupled internal and external fields could halt, steer or reverse the direction
      the motor inside a microchannel, rotate the motor around a target, and deliver
      the motor to a cluster of cells. This study showcases a multimodal chemical
      magnetic field regulated migration of micro-machines for sensing, transport, and
      delivery inside a fluidic environment. 

PMID- 24310181
TI  - Ribosomal RNA integrity and rate of seed germination.
AB  - The integrity of ribosomal RNA (the percentage of complete, un-nicked molecules)
      in seeds was studied by electrophoresis under denaturing conditions. Two batches
      of carrot seed, harvested at different stages of maturity, and four batches
      ofNicotiana seed stored for various times were used. Within each species, there
      was a correlation between the integrity of the rRNA of the dry seed and the rate
      of germination of that seed. In carrot seed, there was extensive degradation of
      existing rRNA in both the embryo and endosperm during the first two days of
      imbibition. 

PMID- 24310182
TI  - Nitrogen redistribution during grain growth in wheat (Triticum aestivum L.) : I.
      Peptide hydrolase activity and protein breakdown in the flag leaf, glumes and
      stem.
AB  - The activity of a range of endo- and exopeptidase enzymes have been measured in
      the glumes, flag leaf and stem during the period of grain development in wheat.
      The enzymes show a sequential pattern of appearance with activity peaks occurring
      at a number of intervals from anthesis until just prior to the cessation of grain
      growth. Of the enzymes studied only the haemoglobin- and casein-degrading
      activity and alanylglycine-dipeptidase activity increased during the period of
      rapid protein loss, while aminopeptidase, carboxypeptidase and leucyltyrosine
      dipeptidase reached maximum activity prior to this period. 

PMID- 24310183
TI  - Protein patterns in the oat coleoptile as influenced by auxin and by protein
      turnover.
AB  - Synthesis of growth-limiting proteins (GLP) is required for continued auxin
      induced elongation of oat (Avena sativa L.) coleoptiles. In order to determine
      whether GLP synthesis is dependent or independent of auxin, a double-labeling
      ratio technique, coupled with disc-gel electrophoresis, has been used to assess
      the effect of auxin on the pattern of protein synthesis. Sections were peeled to
      enhance amino-acid uptake; proteins were labeled with [(14)C]- or [(3)H] leucine
      in the presence or absence of indole-3-acetic acid for 40 min to 6 h, and were
      separated into soluble, membrane-associated, and wall-associated fractions.
      Regardless of the conditions used, or the protein fraction examined, no changes
      in response to auxin were detected in the pattern of protein synthesis. In order
      to escape detection by this technique an auxin-induced protein would have to
      comprise less than 0.75% of the total newly synthesized protein. Thus the
      synthesis of GLP appears to be independent of auxin. The same technique has been
      used to follow protein turnover. During the chase, proteins are initially
      degraded at an average rate of 8% h(-1), and some protein bands showed as much as
      14% h(-1) degradation. No protein was detected which had a turnover rate as rapid
      as the GLP. 

PMID- 24310184
TI  - Changes in chloroplast number during pea leaf development : An analysis of a
      protoplast population.
AB  - Protoplasts were prepared from pea (Pisum sativum L.) leaves throughout
      development and their contents spread in a monolayer to determine the number of
      chloroplasts per cell. This approach permitted the rapid analysis of more than
      100 cells at each stage of development. The average number of chloroplasts per
      cell increased from 24+/-10 to 64+/-20 during greening and expansion of the first
      true foliage leaves; all cells containing chloroplasts apparently increase their
      chloroplast number. A parallel increase in the amount of DNA per nucleus was not
      observed. As the leaves senesced the chloroplast number gradually decreased to
      44+/-12. We have correlated these changes with our previous results on the
      percentage of chloroplast DNA per cell. Chloroplast multiplication resulted in a
      2.7-fold dilution (from 272 to 102) of the number of copies of the chloroplast
      DNA molecule per plastid. 

PMID- 24310185
TI  - Polyadenylated mRNA for the light-harvesting chlorophyll a/b protein : Its
      presence in green and absence in chloroplast-free plant cells.
AB  - In thylakoid membranes isolated from green plants of parsley, pea, and barley,
      the light-harvesting chlorophyll a/b protein complex (LHCP, mol. weight: 25,000),
      is a major constituent. Poly(A)RNA isolated from these species was translated in
      a wheat germ, cell-free system. The in vitro translation products were treated
      with antibodies raised against the LHCP. This treatment resulted in the
      precipitation of a precursor protein (mol. weight: 29,000). Poly(A)RNA was also
      prepared from a cell culture ofPetroselinum that does not develop chloroplasts
      upon illumination. This poly(A)RNA is capable of stimulating amino acid
      incorporation in the in vitro translation system, however, it does not direct the
      synthesis of LHCP. 

PMID- 24310186
TI  - Kinetics of the appearance of mRNA for light-harvesting chlorophyll a/b protein
      in polysomes of barley.
AB  - Polysomes from dark-grown and illuminated barley seedlings were translated in
      cell-free systems. The translation products reacting with the antibody against
      the light-harvesting chlorophyll a/b protein (LHCP) were analyzed by
      polyacrylamide gel electrophoresis. It was found that, in addition to the
      precursor protein of LHCP, a product was obtained that co-migrated with the
      mature protein. Furthermore, the results show that the light-induced proly(A)RNA
      for LHCP is integrated into the polysomal complex without delay, indicating that
      the integration of LHCP into the membrane is controlled at a higher level of gene
      expression. 

PMID- 24310187
TI  - Comparison of proteins synthesized in vivo and in vitro by mRNA from isolated
      protoplasts.
AB  - Studies of proteins synthesized in vitro by messenger RNA (mRNA) extracted from
      tobacco protoplasts showed that the changes in protein synthesis and especially
      the lack of certain proteins observed previously in isolated protoplasts did not
      result from a failure of translation. 

PMID- 24310188
TI  - The effect of differential root and shoot temperature on the nitrate reductase
      activity, assayed in vivo and in vitro in roots ofHordeum vulgare (barley) :
      Relationship with diurnal changes in endogenous malate and sugar.
AB  - There was a large increase in nitrate reductase activity (NAR) assayed both in
      vivo and in vitro in roots of barley plants (cv. Midas_ grown with roots at 10
      degrees C and shoots at 20 degrees C, compared with whole plants grown at 20
      degrees C. There were diurnal fluctuations in NRA in roots from both treatments,
      but they were much greater in roots grown at 20 degrees C, where NRA fell to a
      very low value in the dark period. The diurnal fluctuations in the malate content
      of the roots were also related to the root growth temperature. Plants with roots
      grown at the lower temperature had a higher malate content, especially in the
      dark period where it was 20 times greater than in plants with roots at 20 degrees
      C. At all times there was a three-fold increase in soluble carbohydrate in cooled
      roots and diurnal fluctuations were much less pronounced than those of malate.
      Growth at low temperatures increased the total flux of amino N into the xylem sap
      and increased the proportion of reduced N in the total N flux. At certain times
      of day both 10 degrees C- and 20 degrees C-grown roots responded to exogeneous
      malate by increasing the flux of amino acid into the xylem sap, although this
      effect was always more pronounced in 20 degrees C-grown roots. 

PMID- 24310189
TI  - Influence of leaves and roots on meristem development inNicotiana tabacum L. cv.
      Wisconsin 38.
AB  - The terminal, apical shoot meristem ofN. tabacum cv. Wisconsin 38 normally
      differentiates into a flower after producing 30 to 40 nodes. The influence of
      leaves and roots on the regulation of flowering was evaluated by counting the
      number of nodes produced after removal of leaves or the induction of adventitious
      roots. Leaf removal has no effect on the number of nodes produced before flower
      formation. Root induction significantly increases the number of nodes produced
      before flower formation. The plant behaves as if it were measuring the number of
      nodes between the meristem and the roots as a means of regulating meristem
      conversion from vegetative to floral differentiation. 

PMID- 24310190
TI  - Composition of suberin-associated waxes from the subterranean storage organs of
      seven plants : Parsnip, carrot, rutabaga, turnip, red beet, sweet potato and
      potato.
AB  - The waxes associated with the suberin in the periderm of the underground storage
      organs of parsnip (Pastinaca sativa L.), carrot (Daucus carota L.), rutabaga
      (Brassica napobrassica Mill.), turnip (Brassica rapa L.), red beet (Beta vulgaris
      L.), sweet potato (Ipomoea batatas L.) and potato (Solanum tuberosum L.) were
      isolated, fractionated into hydrocarbon, wax ester, free fatty alcohol and free
      fatty acid fractions, and analyzed by combined gas chromatography and mass
      spectrometry. The amount of wax extracted from the periderm of the storage organs
      ranged from 2 to 32 MUg/cm(2). The hydrocarbons from the suberin layer have a
      broader chain-length distribution, a predominance of shorter carbon chains, and a
      higher proportion of even-numbered carbon chains than the leaf alkanes from the
      same plants. The major components of the free and esterified fatty alcohols and
      fatty acids have an even number of carbon atoms, and are similar in chain-length
      distribution to their counterparts found covalently attached to the suberin
      polymers; however, these suberin components are shorter in chain length than
      their cuticular analogues from the leaves. Also extracted from the storage organs
      were polar components which included fatty alcohols and fatty acids in a
      conjugated form, and omega-hydroxy acids and dicarboxylic acids. Evidence is
      presented that removal of the wax from the periderm of whole storage organs
      results in a decrease in diffusion resistance to moisture. 

PMID- 24310191
TI  - Enzymes of nitrogen assimilation in maize roots.
AB  - The enzymes nitrate reductase (NR), glutamate dehydrogenase (GDH), glutamate
      synthase (GOGAT), glutamine synthetase (GS) and asparagine synthetase (AS) have
      been assayed in various regions along the seedling root ofZea mays L. In the
      intact attached root and calculated on a protein basis NR, GOGAT, and GS are
      found to have slightly higher specific activities in the apical 5 mm than in more
      mature regions of the root. GDH and AS, on the other hand, are much more active
      in extracts prepared from mature regions of the root than in the apical region.
      In excised root tips incubated in the presence of NH4 (+) and NO3 (-) there was a
      marked increase in GDH and AS, and a slight decrease in GOGAT and GS. Additions
      of NO3 (-) are required for NR activity but neither NO3 (-) nor NH4 (+) additions
      altered the activity levels of the other four enzymes. Additions of glucose to
      the medium inhibited the development of AS and GDH activities and resulted in
      higher activity levels of NR, GS and GOGAT. Glucose additions also enhanced the
      incorporation of acetate-(14)C and leucine-(14)C into protein. Additions of
      cycloheximide inhibit the development of NR, AS and GDH activities and also the
      incorporation of acetate-(14)C and leucine into protein. 

PMID- 24310192
TI  - Interaction of [(3)H]gibberellin A 1 with a sub-cellular fraction from lettuce
      (Lactuca sativa L.) hypocotyls : The relationship between growth and
      incorporation.
AB  - The relationship between elongation growth and the incorporation of
      [(3)H]gibberellin A1 ([(3)H]GA1) into a 2,000g pelletable (2KP) fraction from
      lettuce (Lactuca sativa L., cv. Arctic) hypocotyl sections has been examined.
      Sections were loaded with incremental amounts of GA1 under conditions where
      growth was arrested (5 degrees  C) or permitted (30 degrees  C) and, after 16 h,
      all were transferred to a GA-free medium at 30 degrees  C. Growth and 2KP
      radioactivity were measured at this point and after a further 24 h in the chase
      medium. Uptake was reduced by 80% at 5 degrees  C, as compared to 30 degrees  C,
      but 2KP labelling and protein synthesis were only reduced by half. The growth
      rate of the 5 degrees  C pretreated sections during the chase period was
      comparable to that observed during the pulse in the 30 degrees  C material but
      the dose/response relationship was flatter. Low temperature sections incorporated
      a much higher percentage of GA1 uptake into the 2KP fraction (27% at maximum) but
      the absolute levels of labelling at this temperature were lower than those
      measured at 30 degrees  C. The data are interpreted as showing that 2KP labelling
      is not a consequence of growth. It must either precede response or be an
      unconnected concurrent process. 

PMID- 24310193
TI  - Polysomes from expanded tobacco leaves.
AB  - The isolation of intact polysomes from leaves of tobacco (Nicotiana tabacum L.)
      is dependent on the age and state of development of leaves. Undegraded polysomes
      from young leaves in the early stages of expansion can be isolated easily by
      extracting the leaves in ice-cold extraction buffer (200 mM
      tris(hydroxymethyl)aminomethylmethane(Tris)-HCl, pH 9.0; 400 mM KCl; 200 mM
      sucrose; 35 mM MgCl2). Medium-size leaves give best yields of undegraded
      polysomes when extractions are carried out in the above buffer and in the
      presence of ethyleneglycol-bis-(beta-amino-ethyl ether)-N,N'-tetracetic acid
      (EGTA) and mercaptoethanol. Isolation of polysomes from large, nearly fully
      expanded (mature) leaves requires all of the above plus diethyldithiocarbamate
      (DIECA) in the extraction medium. An extraction medium consisting of 25 mM EGTA,
      0.01 M mercaptoethanol, 25 mM DIECA and 0.5% of the nonionic detergent, Nonidet
      P40 (NP 40) was found to be very suitable for extraction of polysomes from all
      developmental stages of leaves. The polysomes extracted in the above medium
      showed active translation of protein in the wheat-germ in-vitro protein
      synthesizing system. The translational products were similar when translations
      were carried out directly with polysomes or polysomal RNA, or polysomal
      poly(A)(+) RNA from tobacco leaves. Poly(A)(-) polysomal RNA was a poor template
      in the in-vitro wheat-germ system. 

PMID- 24310194
TI  - The nature of callose produced during self-pollination inSecale cereale.
AB  - The response to incompatible (self) pollination in rye (Secale cereale L.)
      includes the rapid deposition in the germinating pollen grain and pollen tube of
      a substance that stains with aniline blue, resorcin blue and calcofluor, and in
      these respects resembles callose. This substance has been isolated and analysed
      by acid hydrolysis and methylation as well as specific enzyme hydrolysis. It
      contains a glucan component with 1,4-beta-glucosidic and 1,3-beta-glucosidic
      linkages within the same linear chains. The proportion of 1,4-to 1,3-glucosidic
      linkages in the preparation is 77?9. 

PMID- 24310195
TI  - Auxin action on proton influx in corn roots and its correlation with growth.
AB  - At concentrations inhibitory to the elongation of corn (Zea mays L.) roots, the
      auxins, indole-3-acetic acid (IAA) and alpha-naphthaleneacetic acid (alpha-NAA),
      cause an increase in the pH of the bathing medium; this increase occurs with an
      average latent period shorter than the latent period for the inhibitory effect of
      these auxins on elongation. Indole-2-carboxylic acid, an inactive structural
      analogue of IAA, and beta-naphthaleneacetic acid, an inactive analogue of alpha
      NAA, affect neither growth nor the pH of the medium. Since acid pH is known to
      promote and basic pH to inhibit root elongation, the data are consistent with the
      hypothesis that hormone-induced modification of cell-wall pH plays a role in the
      control of elongation of roots, as has been proposed for elongation of stems and
      coleoptiles. 

PMID- 24310196
TI  - Some features of the inheritance of avenins, the alcohol soluble proteins of oat.
AB  - The inheritance of avenin components, the prolamins (or alcohol soluble proteins)
      of Avena, is studied by means of gel electrophoresis. Avenin is composed of
      rather similar proteins which appear as a polymorphic group from a biochemical
      point of view. After a first preliminary investigation it showed a surprisingly
      high interspecific variability. The average number of its constituents increases
      with the ploidy level but it still is much lower than that of wheat gliadin.The
      avenin electrophoretic patterns of 47 samples (F4, F5 or F6 seeds) resulting from
      3 hexaploid crosses are compared with the parental patterns. Four kinds of
      inheritance are observed. Roughly 50% of progeny profiles are identical to those
      of one of the parents. They are composed occasionally of partial sections of
      parental patterns. Complete additiveness occurs rather seldom. However, in one of
      the crosses a significant number of progeny samples show a band, one of the very
      slow moving constituents, which was not present in either of the parents.The
      study of avenin in F1 seeds, arising from reciprocal crosses between two
      homozygous parent plants, shows a significant effect of maternal gene dose in the
      triploid endosperm.Because of both the variability and the relatively small
      number of avenin constituents, these results show that typical endosperm proteins
      such as oat prolamin constitute a useful tool for phylogenetic studies of the
      genus Avena. 

PMID- 24310197
TI  - Fertilization and early embryo development in reciprocal interspecific crosses of
      Phaseolus.
AB  - Fertilization and early embryo and endosperm development were examined in
      Phaseolus vulgaris x P. acutifolius, P. vulgaris x P. lunatus crosses and their
      reciprocals. The number and length of pollen tubes were not different between
      selfings and interspecific crosses. Fertilization was completed in all matings
      and the time of fertilization was maternally dependent which may reflect the
      degree of maturation of embryo sacs at pollination. A large difference between
      reciprocal crosses was found in the time of endosperm and embryo division in
      relation to the time of fertilization. When P. vulgaris was the female parent and
      P. acutifolius the male parent, endosperm division occurred at the same time as
      in P. vulgaris upon selfing, while in P. vulgaris x P. lunatus crosses the time
      of endosperm division was intermediate as compared with the two parents. The time
      lapse between fertilization and endosperm and embryo division in P. acutifolius x
      P. vulgaris crosses was longer than in either parent upon selfing. In P. lunatus
      x P. vulgaris crosses, endosperm division occurred in only 7-12% of the ovules at
      72 hours after pollination. Embryo development in these ovules was limited to the
      four cell stage although the endosperm was at the free nuclei stage. The severe
      delay in embryo and endosperm divisions may be the major cause of early pod
      abscission in P. lunatus x P. vulgaris crosses. 

PMID- 24310198
TI  - Homoeologous chromosomal location of the genes encoding thionins in wheat and
      rye.
AB  - Thionins are high sulphur basic polypeptides present in the endosperm of
      Gramineae. In wheat there are three thionins encoded by genes located in the long
      arms of chromosomes 1A, 1B and 1D. Rye has one thionin encoded by a gene which
      has been assigned to chromosome 1R after analysis of the Imperial-Chinese Spring
      rye-wheat disomic addition lines. Commercial varieties and experimental stocks
      with a 1B/1R substitution carry the thionin from rye (beta R) instead of the
      alpha B thionin from wheat. The beta R thionin gene is not located in the large
      chromosomal segment representing most of the short arm of chromosome 1R. 

PMID- 24310199
TI  - Rye B chromosome behaviour at first and second pollen mitosis and its
      relationship with anther maturity.
AB  - Rye plants carrying B chromosomes with different nuclear and cytoplasmic
      constitutions have been analyzed at first pollen mitosis. No differences of B
      chromosome behaviour have been detected. It has been concluded that non
      disjunction and preferential distribution are processes controlled by Bs
      themselves.At second pollen anaphase, B laggards have been observed. Both non
      disjunction and B laggards occurred with higher frequency in younger anthers. 

PMID- 24310200
TI  - Genetic divergence in various Sahiwal x Holstein crossbred grades.
AB  - The degree of genetic divergence using Mahalanobis's D(2) statistic and the
      clustering pattern using canonical variate analysis between Sahiwal and its 39
      Friesian grades were studied for 9 characters of economic importance. The records
      were adjusted for the significant effects due to farms, periods and seasons.
      Forty grades were grouped into 11 clusters. The results have shown that in cattle
      when two breeds of diverse origin, one of superior merit and the other relatively
      inferior, are crossed in a scheme of forward crossing, there is no linear
      increase in production level above 50% with the increase in genes of the superior
      parent. It can not be assumed that grading up to a total replacement of genes
      will lead to higher levels of production at least in cattle. In order to
      stabilize a breed type from such a crossbred population a breeding plan has been
      proposed. 

PMID- 24310201
TI  - Role of local germplasm and induced mutations in the improvement of the protein
      content in rice.
AB  - Ninety local cultivars and 124 induced grain shape mutants were screened for
      their protein content and the distribution of protein in their endosperm. The
      protein content varied widely from 4.2 to 12.1% in the local varieties and from
      5.5 to 13.7% in the mutants. Some high protein lines like 'Chinnavadlu',
      'Budumavadlu', etc. with more than 10.0% protein were identified. Protein
      distribution studies have shown that several mutants, such as IR-8-FG-28, IR-8-FG
      33, etc., have a deeper distribution of protein bodies and some local cultivars,
      like 'Kakathya' and 'Muchulu', have a relatively more uniform distribution of
      protein in the endosperm. The protein content at different milling levels
      revealed that at 12% milling the percentage retention of protein varied from
      about 79 to 96% irrespective of the percentage of protein, suggesting that the
      distribution of protein, in addition to the protein content, plays an important
      role in nutritive value of rice. 

PMID- 24310202
TI  - Haplopappus gracilis cell strains resistant to pyrimidine analogues.
AB  - Strains of Haplopappus gracilis (Nutt.) Gray cells resistant to 6-azauracil have
      been isolated from cultures of diploid cells. These strains are also resistant to
      8-azaguanine, as is their parent. The variants are 100- to 125-fold more
      resistant to 6-azauracil than their parent, and they exhibit different spectra of
      cross resistance to other pyrimidine analogues. The phenotype of each variant is
      stable in the absence of selection. The majority of cells in cultures of the
      variants are diploid; all others examined were tetraploid. Initial rates of
      uptake of uracil are not reduced in the variants. Fluorouracil, to which two
      variants are resistant, is taken up by one of them as well as by the parent.
      Responses of the other two to fluorouracil are not correlated with decreased
      ability to accumulate this analogue. 

PMID- 24310203
TI  - Comparative electrophoretic studies of proteins and enzymes of some Brassica
      species.
AB  - A considerable amount of variation with respect to soluble proteins and esterase
      isoenzyme pattern was observed between different species of Brassica. Naturally
      occurring amphidiploids had comparable proteins and isoenzyme patterns to either
      one or both of the parental species. The species relationship based on percentage
      homology of protein and esterase bands revealed that B. nigra and B. campestris
      are the parental species of B. carinata and not B. nigra and B. oleracea, as
      suggested on the basis of cytological studies. Elimination of a pair of
      chromosomes might have resulted into 2n=34 in the case of B. carinata. Further
      studies are needed to confirm this view. The peroxidase and catalase isoenzyme
      patterns did not show much variation in different species and amphidiploids. 

PMID- 24310204
TI  - Correction.

PMID- 24310205
TI  - Source apportionment and distribution of polycyclic aromatic hydrocarbons, risk
      considerations, and management implications for urban stormwater pond sediments
      in Minnesota, USA.
AB  - High concentrations of polycyclic aromatic hydrocarbons (PAHs) are accumulating
      in many urban stormwater ponds in Minnesota, resulting in either expensive
      disposal of the excavated sediment or deferred maintenance by economically
      challenged municipalities. Fifteen stormwater ponds in the Minneapolis-St. Paul,
      MN, metropolitan area were studied to determine sources of PAHs to bed sediments
      through the application of several environmental forensic techniques, including a
      contaminant mass balance receptor model. The model results were quite robust and
      indicated that coal tar-based sealant (CT-sealant) particulate washoff and dust
      sources were the most important sources of PAHs (67.1%), followed by vehicle
      related sources (29.5%), and pine wood combustion particles (3.4%). The
      distribution of 34 parent and alkylated PAHs was also evaluated regarding
      ancillary measurements of black carbon, total organic carbon, and particle size
      classes. None of these parameters were significantly different based on major
      land-use classifications (i.e., residential, commercial, and industrial) for pond
      watersheds. PAH contamination in three stormwater ponds was high enough to
      present a risk to benthic invertebrates, whereas nine ponds exceeded human health
      risk-based benchmarks that would prompt more expensive disposal of dredged
      sediment. The State of Minnesota has been addressing the broader issue of PAH
      contaminated stormwater ponds by encouraging local municipalities to ban CT
      sealants (29 in all) and to promote pollution prevention alternatives to
      businesses and homeowners, such as switching to asphalt-based sealants. A
      statewide CT-sealant ban was recently enacted. Other local and regional
      jurisdictions may benefit from using Minnesota's approach where CT-sealants are
      still used.

PMID- 24310208
TI  - Retrospective analysis of first-line anti-vascular endothelial growth factor
      treatment patterns in wet age-related macular degeneration.
AB  - INTRODUCTION: This study compared the number of, and expenditures on, first-line
      intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections
      between patients who were treated with aflibercept or ranibizumab for wet age
      related macular degeneration (AMD). METHODS: This was a retrospective cohort
      study based on U.S. administrative claims data. Selected patients had initiated
      first-line intravitreal anti-VEGF treatment with ranibizumab or aflibercept
      (index date) between November 18, 2011 and April 30, 2013, were aged >= 18 years
      on the index date, had 12 months of continuous insurance enrollment prior to the
      index date (baseline period), were diagnosed with wet AMD during the baseline
      period or on the index date, and had at least 6 or 12 months of follow-up
      enrollment after the index date without switching to a different anti-VEGF agent
      (follow-up periods). Outcomes measured within the 6 and 12 month follow-up
      periods included the number of, and healthcare expenditures on, intravitreal anti
      VEGF injections. Multivariable regressions compared the outcomes between
      aflibercept and ranibizumab. RESULTS: The 6 months analyses included 319
      aflibercept patients and 1,054 ranibizumab patients (12 month analyses: 57 and
      374, respectively). Over the first 6 months after the index date, neither the
      number of injections (aflibercept mean = 3.8 +/- 1.6; ranibizumab mean = 3.9 +/-
      1.9) nor the expenditures on injections (aflibercept mean = $7,468 +/- $4,211;
      ranibizumab mean = $7,816 +/- $4,834) differed significantly between aflibercept
      patients and ranibizumab patients (in multivariable regression treating
      ranibizumab as reference: incidence rate ratio = 0.97, 95% confidence interval
      [CI] 0.91-1.03, P = 0.277; cost ratio = 0.96, 95% CI 0.89-1.04, P = 0.338).
      Differences were also insignificant in the 12 month analyses. The overall mean
      days between injections differed by only 1.8 (95% CI 1.3-2.3) days between the
      aflibercept patients and ranibizumab patients (42.4 and 40.6, respectively).
      CONCLUSION: Aflibercept and ranibizumab were used at a similar frequency
      resulting in similar intravitreal anti-VEGF injection healthcare expenditures
      among wet AMD patients initiating first-line intravitreal anti-VEGF treatment.

PMID- 24310209
TI  - Carbohydrate linked organotin(IV) complexes as human topoisomerase Ialpha
      inhibitor and their antiproliferative effects against the human carcinoma cell
      line.
AB  - Dimethyltin(IV) complexes with ethanolamine (1) and biologically significant N
      glycosides (2 and 3) were designed and synthesized. The structural elucidation of
      complexes 1-3 was done using elemental and spectroscopic methods; in addition,
      complex 1 was studied by single crystal X-ray diffraction studies. The in vitro
      DNA binding profile of complexes 2 and 3 was carried out by employing different
      biophysical methods to ascertain the feasibility of glycosylated complexes.
      Further, the cleaving ability of 2 and 3 was investigated by the agarose gel
      electrophoretic mobility assay with supercoiled pBR322 DNA, and demonstrated
      significantly good nuclease activity. Furthermore, both the complexes exhibited
      significant inhibitory effects on the catalytic activity of human Topo I at lower
      concentration than standard drugs. Computer-aided molecular docking techniques
      were used to ascertain the mode and mechanism of action towards the molecular
      target DNA and Topo I. The cytotoxicity of 2 and 3 against human hepatoma cancer
      cells (Huh7) was evaluated, which revealed significant regression in cancerous
      cells as compared with the standard drug. The antiproliferative activities of 2
      and 3 were tested against human hepatoma cancer cells (Huh7), and results showed
      significantly good activity. Additionally, to validate the remarkable
      antiproliferative activity of complexes 2 and 3, specific regulatory gene
      expression (MMP-2 and TGF-beta) was obtained by real time PCR.

PMID- 24310210
TI  - Antitrypanosomal isothiocyanate and thiocarbamate glycosides from Moringa
      peregrina.
AB  - O-Methyl (1), O-ethyl (2), and O-butyl (3) 4-[(alpha-L-rhamnosyloxy) benzyl]
      thiocarbamate (E), along with 4-(alpha-L-rhamnosyloxy) benzyl isothiocyanate (4)
      have been isolated from the aerial parts of Moringa peregrina. The compounds were
      tested for in vitro activity against Trypanosoma brucei rhodesiense and
      cytotoxicity in rat skeletal myoblasts (L6 cells). The most potent compound was 4
      with an IC50 of 0.10 uM against T.b. rhodesiense and a selectivity index of 73,
      while the thiocarbamate glycosides 1, 2, and 3 showed only moderate activity.
      Intraperitoneal administration of 50 mg/kg body weight/day of 4 in the T.b.
      rhodesiense STIB 900 acute mouse model revealed significant in vivo toxicity.
      Administration of 10 mg/kg body weight/day resulted in a 95% reduction of
      parasitemia on day 7 postinfection, but did not cure the animals. Because of its
      high in vitro activity and its ability to irreversibly inhibit trypanothione
      reductase, an attractive parasite-specific target enzyme, 4-[(alpha-L
      rhamnosyloxy) benzyl] isothiocyanate (4), can be considered as a lead structure
      for the development and characterization of novel antitrypanosomal drugs.

PMID- 24310211
TI  - Selective estrogen receptor modulator effects of epimedium extracts on breast
      cancer and uterine growth in nude mice.
AB  - Epimedium is popularly used in traditional Chinese medicine to treat sexual
      dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of
      the prenylated flavonoids of Epimedium make it an attractive alternative for
      hormone replacement therapy. Here, we examined the therapeutic potential of the
      estrogenic herb extract of Epimedium brevicornum as an alternative to hormone
      replacement therapy in a breast cancer mouse model. To that end, athymic and
      ovariectomized female nude mice were subcutaneously injected into the mammary fat
      pads with MCF-7 breast cancer cells, randomly grouped and fed with soy-free
      feeds, alone or in combination with ethinyl estradiol or different doses of the
      estrogenic herb extract of E. brevicornum. Our findings demonstrate that unlike
      ethinyl estradiol, it did not promote the growth of breast cancer xenograft
      volume and weight, with the highest dose showing a significant reduction in
      growth and ERalpha protein content. Moreover, the extract increased uterine
      weight at the lowest dose, while higher doses had no effects. Put together, our
      data shows for the first time that despite the estrogenic activity of E.
      brevicornum, its action is largely tissue specific and dose-dependent. Our data
      on E. brevicornum presents in vivo evidence for its selective estrogen receptor
      modulator effect and warrants exploration of its use as an alternative to hormone
      replacement therapy in menopausal women. 

PMID- 24310213
TI  - Natural product libraries: assembly, maintenance, and screening.
AB  - This review discusses successful strategies and potential pitfalls to assembling
      a natural product-based library suitable for high-throughput screening. Specific
      extraction methods for plants, microorganisms, and marine invertebrates are
      detailed, along with methods for generating a fractionated sub-library. The best
      methods to store, maintain and prepare the library for screening are addressed,
      as well as recommendations on how to develop a robust high-throughput assay.
      Finally, the logistics of moving from an assay hit to pure bioactive compound are
      discussed.

PMID- 24310212
TI  - Screening of natural compounds as activators of the keap1-nrf2 pathway.
AB  - Nuclear factor erythroid 2-related factor 2 is a master regulator that promotes
      transcription of cytoprotective genes in response to oxidative/electrophilic
      stress. A large number of natural dietary compounds are thought to protect
      against oxidative stress, and a few have been reported to induce genes involved
      in antioxidant defense through activating nuclear factor erythroid 2-related
      factor 2. Therefore, a library of 54 natural compounds were collected to
      determine whether they are nuclear factor erythroid 2-related factor 2 activators
      and to compare their efficacy and potency to activate nuclear factor erythroid 2
      related factor 2. The assay utilized AREc32 cells that contain a luciferase gene
      under the control of antioxidant response element promoters. Each natural
      compound was tested at 13 concentrations between 0.02 and 30 uM. Known nuclear
      factor erythroid 2-related factor 2 activators tert-butylhydroquinone and 2-cyano
      3,12-dioxooleana-1,9-diene-28-imidazolide were used as positive controls in
      parallel with the natural compounds. Among the 54 tested natural compounds,
      andrographolide had the highest efficacy, followed by trans-chalcone,
      sulforaphane, curcumin, flavone, kahweol, and carnosol, all of which had better
      efficacy than tert-butylhydroquinone. Among the compounds tested, 2-cyano-3,12
      dioxooleana-1,9-diene-28-imidazolide was the most potent, having an EC50 of 0.41
      uM. Seven of the natural compounds, namely andrographolide, trans-chalcone,
      sulforaphane, curcumin, flavone, kahweol, and cafestol had lower EC50 values than
      tert-butylhydroquinone but higher than 2-cyano-3,12-dioxooleana-1,9-diene-28
      imidazolide. The present study provides insights into which natural compounds
      activate the Keap1-nuclear factor erythroid 2-related factor 2 pathway and thus
      might be useful for detoxifying oxidative/electrophilic stress. 

PMID- 24310214
TI  - The mystery of the occluded port that allowed blood withdrawal: is it safe to use
      standard needles to access ports? A case report and literature review.
AB  - A frequent complication of totally implantable central venous access devices
      (TIVADs) is withdrawal occlusion. We describe a case of rare dysfunction of
      TIVADs: blood withdrawal was possible, whereas infusion was not. A further
      investigation demonstrated that during infusion, a silicone core, probably
      produced by hypodermic needle puncture, occluded the reservoir outlet hole. The
      silicone septum puncture by standard needles instead of non-coring ones may
      reduce the device effectiveness and expose patients to serious complications.

PMID- 24310215
TI  - Oviposition and feeding preferences of the southern pine coneworm (Lepidoptera:
      Pyralidae) for different host-plant materials and observations on monoterpenes as
      an oviposition stimulant.
AB  - Bioassays were conducted with first-stage larvae and newly emerged females of the
      southern pine coneworm,Dioryctria amatella (Hulst), to detect feeding and
      ovipositional preferences for different host-plant materials collected between
      April and August. Correlations between measures of insect preferences and
      estimates of wood parameters indicated that larvae preferred to feed on host
      plant materials with high moisture contents, low wood densities, and low
      monoterpene contents. Female moths, however, did not necessarily select those
      plant materials preferred by larvae for feeding, but tended to oviposit more
      frequently on materials with high monoterpene contents. A synthetic mixture of
      monoterpenes similar in composition to those present in fusiform rust galls of
      slash pine (Pinus elliottii) Englem. var.elliottii) elicited mating and
      oviposition behavior. 

PMID- 24310216
TI  - Insecticidal chromenes from the volatile oil ofHemizonia fitchii.
AB  - Based on field observations of the effects of the resinous tarweedHemizonia
      fitchii A. Gray (Asteraceae) on mosquito populations in California, the volatile
      oil of this plant was investigated for insecticidal activity. Analysis of the oil
      by TLC and capillary GC-MS showed the presence of five major constituents which
      were identified as the monoterpenoid 1,8-cineole, and the chromenes encecalin,
      eupatoriochromene (desmethylencecalin), 6-vinyl-7-methoxy-2,2-dimethylchromene,
      and desmethoxyencecalin. Trace amounts of several volatile fatty acids, alkanes,p
      coumarate derivatives, additional chromene derivatives, and numerous mono- and
      sesquiterpenoids were also detected and identified by GC-MS. Fractionation of the
      oil by preparative TLC and column chromatography afforded the major chromenes,
      the identities of which were confirmed by NMR and IR spectral data. The chromenes
      exhibited weak to moderate toxicity againstCulex pipiens (house mosquito) larvae
      andOncopeltus fasciatus (large milkweed bug) nymphs. However, no antijuvenile
      hormone activity was observed for any of the compounds tested against these
      insect species. 

PMID- 24310217
TI  - Chemical defense of a dorid nudibranch,Glossodoris quadricolor, from the red sea.
AB  - The nudibranch,Glossodoris quadricolor (Doridacea) feeds on the red
      spongeLatrunculia magnifica, which grows in the reefs of the Gulf of Aqaba, Red
      Sea. The ichthyotoxic substance from the sponge, latrunculin B, was also
      indentified in the mucous secretion of the mollusk by TLC, indicating the use of
      this substance as defense allomone. 

PMID- 24310218
TI  - Identification of volatile sex pheromone components released by the southern
      armyworm,Spodoptera eridania (Cramer).
AB  - Analysis of sex pheromone gland extracts and volatile pheromone components
      collected from the calling female southern armyworm,Spodoptera eridania (Cramer),
      by high-resolution capillary gas chromatography and mass spectroscopy indicated
      that a number of 14-carbon mono- and diunsaturated acetates and a monounsaturated
      16-carbon acetate were produced. Gland extracts also indicated the presence of
      (Z)-9-tetradecen-1-ol. However, this compound was not found in collections of
      volatiles. Field trapping studies indicated that the volatile blend composed of
      (Z)-9-tetradecen-1-ol acetate (60%), (Z)-9-(E)-12-tetradecadien-1-ol acetate
      (17%), (Z)-9-(Z)-12-tetradecadien-1-ol acetate (15%), (Z)-9-(E)-11-tetradecadien
      1-ol acetate (5%), and (Z)-11-hexadecen-1-ol acetate (3 %) was an effective trap
      bait for males of this species. The addition of (Z)-9-tetradecen-1-ol to the
      acetate blends tested resulted in the capture of beet armyworm,S. exigua
      (Hubner), males which provides further evidence that the alcohol is a pheromone
      component of this species. 

PMID- 24310219
TI  - Sex attractants for Geometrid and Noctuid moths : Field trapping and
      electroantennographic responses to triene hydrocarbons and monoepoxydiene
      derivatives.
AB  - Male moths belonging to 17 species of Geometridae and nine species of Noctuidae
      were captured in traps baited with synthetic chemicals as part of a field
      screening program. The compounds tested were the C18-C22 homologs of: (1)
      (3Z,6Z,9Z)-triene hydrocarbons; (2) mixtures containing equal quantities of
      (3Z,6Z)-cis-9,10-expoxydienes, (3Z,92Z)-cis-6,7-epoxydienes, and (6Z,9Z)-cis-3,4
      epoxydienes; (3) (3Z,6Z)-9S,10R-epoxydienes; (4) (3Z,6Z)-9R,10S-epoxydienes; and
      (5) (3Z,6Z,9Z,11E)-nonadecatetraene. Field captures and electroantennographic
      assays revealed a high degree of specificity in the responses of many species to
      the synthetic chemicals. In several species the ability of males to discriminate
      between the 9S,10R and 9R,10S enantiomers of the monoepoxydiene isomers was
      clearly shown. Synergists and inhibitors were discovered for several of the
      reported attractants, some of which were not previously known to have
      semiochemical activity. The geometrid moths captured includedEpirrhoe sperryi
      (Herbulot),Mesoleuca ruficillata (Guenee),Triphosa haesitata (Guenee),Metanema
      inatomaria (Guenee),Prochoerodes transversata (Drury),Cabera erythemaria
      (Guenee),Synaxis jubararia (Hulst),Dysstroma brunneata ethela (Hulst),Eulithes
      testata (Linnaeus),Sicya macularia (Harris),Xanthorhoe iduata (Guenee),X.
      abrasaria aquilonaria (Herrich-Schaffer),X. munitata (Hubner),Itame loricaria
      (Eversmann),Eupithecia annulata (Hulst),E. rovocastaliata (Packard) andE.
      satyrata dodata (Taylor). The noctuid moths captured includedBleptina
      caradrinalis (Guenee),Idia americalis (Guenee),I. aemula (Hubner),Rivula
      propinqualis (Guenee),Lomanaltes eductalis (Walker),Spargaloma sexpunctata
      (Grote),Caenurgina distincta (Neumuller),Euclidia cuspidea (Hubner), andZale
      duplicata (Bethune). Six of the nine noctuid species captured belong to three
      subfamilies for which sex attractants had not been reported previously. Details
      for the stereospecific synthesis of (3Z,6Z)-cis-9,10-epoxydienes are also
      reported. 

PMID- 24310220
TI  - Field response ofDendroctonus brevicomis toexo-brevicomin, frontalin, and myrcene
      released at two proportions and three levels.
AB  - Racemicezo-brevicomin, racemic frontalin, and myrcene were released at two
      proportions (5?1?400 and 1?1?1), each at three levels (1 *, 10 *, and 100 *) in a
      ponderosa pine forest in central California. The 5?1?400 mix was based on an
      estimate of the relative amounts released from a ponderosa pine under attack by
      the western pine beetle,Dendroctonus brevicomis. MoreD. brevicomis were trapped
      at a source of the three compounds released at 5?1?400 than were trapped at a
      source released at 1?1?1, at all three levels, but this difference was
      statistically significant only at the 1 * and 10 * levels. Sex ratio of trapped
      beetles and distribution of catch at the source of attractant and 5 m away
      apparently did not differ between relative release rates. 

PMID- 24310221
TI  - Electroantennogram responses ofTrirhabda bacharides (weber) (Coleoptera:
      Chrysomelidae) to plant volatiles.
AB  - Electroantennograms (EAGs) were recorded fromTrirhabda bacharides Le Conte
      (Coleoptera: Chrysomelidae) females to 28 odorants and volatiles emanating from
      leaves of 26 plant species including three known host plants,Baccharis
      halimifolia L.,B. neglecta Britt, andB. salicina T. & G. (Compositae: Asterae).
      Antennal receptors were highly responsive to components of the green leaf
      volatile complex, especially 6-carbon saturated and monounsaturated alcohols
      andtrans-2-hexenal. EAGs elicited by heptanal were greater than those elicited by
      any other saturated aldehyde. Oxygenated monoterpenes were more active than
      monoterpene hydrocarbons. beta-Bisabolol was the most active sesquiterpene. In
      general, EAGs to volatiles emanating fromBaccharis and other composite species
      were greater than those elicited by species from other families. Furthermore,
      when one considers only plants occurring in the environs ofT bacharides hostB.
      neglecta, EAGs elicited by its host plant were at least two times greater than
      those elicited by other coinhabiting plants. 

PMID- 24310222
TI  - Kairomones for the egg parasiteTrichogramma evanescens Westwood : I. Effect of
      volatile substances released by two of its hosts,Pieris brassicae L. andMamestra
      brassicae, L.
AB  - In a four-armed airflow olfactometerTrichogramma evanescens Westwood females were
      attracted by a volatile substance(s) released by virgin females of the great
      cabbage white butterfly,Pieris brassicae L. Males or recently mated females did
      not cause attraction. Furthermore,T. evanescens was also attracted by volatiles
      released by calling virgin cabbage moths,Mamestra brassicae L. However, the
      parasites did not respond to (Z)-11-hex-adecenylacetate (the main component of
      the sex pheromone ofM. brassicae), a crude hexane extract of the sex pheromone
      gland, or to males or recently mated females. 

PMID- 24310223
TI  - Kairomones for the egg parasiteTrichogramma evanescens Westwood : II. Effect of
      contact chemicals produced by two of its hosts,Pieris brassicae L. andPieris
      rapae L.
AB  - In observation-cage experiments some new contact kairomones for the egg
      parasiteTrichogramma evanescens Westwood are demonstrated.T. evanescens females
      search significantly longer on cabbage leaves treated with the wing scales of two
      hosts,Pieris brassicae L. andP. rapae L. Further, egg washes ofP. brassicae
      containing an oviposition deterrent pheromone for the butterflies, were found to
      have a contact-kairomonal effect on the parasite.T. evanescens females search
      significantly longer on cabbage leaves sprayed with a methanol or water wash ofP.
      brassicae eggs than on leaves treated with the solvent only. 

PMID- 24310224
TI  - Role of olfaction in host finding by aphid parasitoidAphidius nigripes
      (Hymenoptera: Aphidiidae).
AB  - The olfactory responses of the parasitoidAphidius nigripes Ashmead were
      investigated with a four-field airflow olfactometer. Female and male parasitoids
      did not respond to potato plants, the food plant of their host. However, females
      were strongly attracted by odors from a preferred host,Macrosiphum euphorbiae
      (Thomas), and also from less preferred hosts such asMyzus persicae (Sulzer)
      andAphis nasturtii Kalt. Moreover,A. nigripes females responded positively to
      odors from a nonhost aphid,Rhopalosiphum maidis Fitch. The honeydew produced by
      these four aphid species was also very attractive to females. Males did not
      respond to aphids or honeydew but were highly attracted by odors from conspecific
      female parasitoids. 

PMID- 24310225
TI  - Tests for induction of feeding preferences in larvae of eastern spruce budworm
      using extracts from three host plants.
AB  - Feeding preferences to extracts from three host plants were determined for sixth
      instar eastern spruce budworm larvae reared on one of three hosts or on
      artificial diet. Preferences of foliage-reared larvae were compared to those of
      diet-reared, or naive, larvae. No effect of plant induction was found using amino
      acids and bases and chloroform extracts on test disks in three-choice
      experiments. Possible effects of habituation for sugars and glycosides from white
      spruce were shown. Organic acids contributed to a phenomenon of avoidance
      learning in larvae reared on all three hosts, showing that this fraction from
      balsam fir was the least deterrent, while that from black spruce was the most
      deterrent. 

PMID- 24310226
TI  - Interleukin 17 contributes to the chronicity of inflammatory diseases such as
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint
      destruction and bone resorption. The proinflammatory cytokine interleukin 17 (IL
      17), primarily produced by Th17 cells, has been shown to be involved in all
      stages of the disease and to be an important contributor of RA chronicity. Three
      major processes drive the IL-17-mediated chronicity. Several epigenetic events,
      enhanced in RA patients, lead to the increased production of IL-17 by Th17 cells.
      IL-17 then induces the production of several inflammatory mediators in the
      diseased synovium, which are further synergistically enhanced via combinations of
      IL-17 with other cytokines. IL-17 also promotes the survival of both the
      synoviocytes and inflammatory cells and promotes the maturation of these immune
      cells. This leads to an increased number of synoviocytes and inflammatory cells
      in the synovial fluid and in the synovium leading to the hyperplasia and
      exacerbated inflammation observed in joints of RA patients. Furthermore, these IL
      17-driven events initiate several feedback-loop mechanisms leading to increased
      expansion of Th17 cells and thereby increased production of IL-17. In this
      review, we aim to depict a complete picture of the IL-17-driven vicious circle
      leading to RA chronicity and to pinpoint the key aspects that require further
      exploration. 

PMID- 24310227
TI  - Design, synthesis and evaluation of novel tacrine-rhein hybrids as
      multifunctional agents for the treatment of Alzheimer's disease.
AB  - A series of tacrine-rhein hybrid compounds have been designed and synthesized as
      novel multifunctional potent ChE inhibitors. Most of the compounds inhibited ChEs
      in the nanomolar range in vitro effectively. Compound 10b was one of the most
      potent inhibitors and was 5-fold more active than tacrine toward AChE, and it
      also showed a moderate BuChE inhibition with an IC50 value of 200 nM. Kinetic and
      molecular modeling studies of 10b also indicated that it was a mixed-type
      inhibitor binding simultaneously to the active and peripheral sites of AChE. In
      inhibition of the AChE-induced Abeta aggregation assay, compound 10b (70.2% at
      100 MUM) showed the greatest inhibitory activity. In addition, 10b showed metal
      chelating property and low hepatotoxicity. These results suggested that 10b might
      be an excellent multifunctional agent for AD treatment. 

PMID- 24310228
TI  - Serum levels of cytokines in systemic lupus erythematosus : Association study in
      a Chinese population.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease
      characterized by abnormal production of autoantibodies and proinflammatory
      cytokines. The clear pathogenesis of SLE has not been fully elucidated. Cytokine
      mediated immunity has been showed to be involved in the pathogenesis of SLE.
      OBJECTIVES: The aim of this study was to investigate serum levels of cytokines
      (IL-19, IL-24, IL-26, IL-31, IL-32, IL-36) in SLE patients, in comparison with
      normal controls in a Chinese population. MATERIALS AND METHODS: A total of 65
      patients with SLE and 65 healthy volunteers were recruited for the current study.
      All serum levels of cytokines were measured by enzyme-linked immunosorbent assay
      (ELISA) kits. RESULTS: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL
      36 in SLE patients were not significantly different from the normal controls (all
      p > 0.05). CONCLUSION: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL
      36 in SLE patients were not markedly different from the normal controls. However,
      functional research should be discussed in future studies to elucidate the roles
      of these cytokines in SLE.

PMID- 24310229
TI  - [Recommendations of the German Society for Rheumatology on the perioperative
      approach under therapy with DMARDs and biologicals in inflammatory rheumatic
      diseases].
AB  - BACKGROUND: The perioperative administration of antirheumatic medication can lead
      to an increased risk of infection and to a malfunction in wound healing up to a
      manifest infection; however, the termination of antirheumatic therapy can result
      in a flare up of the disease. Both situations can endanger the success of the
      operation, particularly in arthroplasty. METHOD: The recommendations have been
      developed and approved by the Pharmacotherapy Commission of the German Society
      for Rheumatology following a systematic literature search (as of 30 April 2013)
      and a consensus process. RESULTS: As very little data with sufficiently high
      evidence are available, the present recommendations should be considered as
      having an advisory quality and an individual risk assessment should always be
      carried out. Classical disease-modifying antirheumatic drugs (DMARD), such as
      methotrexate can be continued in normal cases but whether this is also true for
      leflunomide is still undecided. For biologicals a break of two half-life periods
      before the operation is recommended. The therapy can be continued after wound
      healing has been completed and when there are no signs of infection.

PMID- 24310230
TI  - Development of an LC-MS/MS method for the analysis of free sphingoid bases using
      4-fluoro-7-nitrobenzofurazan (NBD-F).
AB  - The molecular species of sphingoid bases were tagged with the fluorescent amino
      group reagent, 4-fluoro-7-nitrobenzofurazan (NBD-F). The NBD-sphingoid bases were
      analyzed by a highly selective and sensitive liquid chromatography-electrospray
      ionization tandem mass spectrometry (LC-ESI-MS/MS) technique capable of reliable
      detection of several fmol of the derivatives. Lipid extracts from plant samples
      were derivatized with NBD-F, and all nine species of free sphingoid bases present
      in plant sphingolipids were separated and quantified for the first time; a
      complete baseline resolution was achieved for cis-8 and trans-8 isomers of
      sphingoid bases by reversed phase HPLC on a C18 column. The extraction and
      derivatization procedures and LC-MS/MS method can facilitate the progress of the
      studies for seeking the active components of sphingoid bases species in response
      to biological challenges. 

PMID- 24310232
TI  - Monograph on hand transplantation.

PMID- 24310231
TI  - In vitro evaluation of enamel demineralization after several overlapping CO2
      laser applications.
AB  - This study aimed to evaluate the effects of repeated CO2 laser applications on
      the inhibition of enamel demineralization. Sixty-five human dental enamel slabs
      were randomly assigned to the following groups (n = 13): control (C), one
      application of the CO2 laser (L1), two applications of the CO2 laser (L2), three
      applications of the CO2 laser (L3), and four applications of the CO2 laser (L4).
      Enamel slabs were irradiated by a 10.6-MUm CO2 laser operating at 5 J/cm(2). The
      slabs were subjected to a pH-cycling regimen and then analyzed by FT-Raman
      spectroscopy, energy-dispersive X-ray fluorescence spectrometry (EDXRF), cross
      sectional micro-hardness, and scanning electron microscopy (SEM). Statistical
      analysis was performed using ANOVA and Tukey tests (p < 0.05). FT-Raman
      spectroscopy showed a reduced carbonate content for L1, L3, and L4 groups when
      compared to C (p < 0.05). The EDXRF data showed no statistical differences
      between the control and irradiated groups for calcium and phosphorus components
      (p > 0.05). Cross-sectional micro-hardness data showed a statistically
      significant difference between the control and all irradiated groups (p < 0.05),
      but no difference was found among the irradiated groups (p > 0.05) up to 30-MUm
      depth. A tendency of lower demineralization occurred in deeper depths for L3 and
      L4 groups. The SEM results showed that with repeated applications of the CO2
      laser, a progressive melting and recrystallization of the enamel surface
      occurred. Repeated irradiations of dental enamel may enhance the inhibition of
      enamel demineralization. 

PMID- 24310233
TI  - Technical implications in proximal forearm transplantation.
AB  - The field of vascularized composite allotransplantation has developed for more
      than a decade. Investigators are defining patient selection criteria, transplant
      indications, immunologic regimens, and tolerance. The majority of the current
      reported hand transplantations have been for treatment of distal forearm or hand
      amputations. In more proximal amputees, the functional outcome of the
      transplanted arm has some unique variables that require a different surgical
      approach. We present a single case of bilateral proximal forearm transplantation
      in effort to describe the unique technical considerations in this complex
      procedure. The surgical procedure is described in detail. At 19 months, our
      patient had 4/5 strength of finger and thumb flexors and protective extensor as
      well as 4/5 wrist flexors and extensors. Our patient had recovery of sensation.
      Our patient now lives independently and does her lower extremity prosthesis
      independently using her hands. These results are expected to continue to improve
      with more time. In hand transplantation, functional results have been very
      promising. The described approach of forearm transplantation allows the transfer
      of the entire functional unit, which should optimize the ultimate outcome for
      these more proximal injuries. 

PMID- 24310234
TI  - Procurement of hand and arm allografts.
AB  - Upper extremity transplantation has been at the forefront of vascularized
      composite allotransplantation. There have been more hand and upper extremity
      transplants than any other kinds of vascularized composite allotransplantation.
      However, it is a new and evolving field. Reconstructive surgeons are relative
      newcomers to the field of transplantation, and the procurement of upper extremity
      allografts has many subtleties that will differ depending on the intended
      recipient. However, there are certain principles that can be adhered to that this
      review serves to elucidate. 

PMID- 24310235
TI  - Contralateral lateral rectus muscle recession in patients with Duane retraction
      syndrome type 3.
AB  - AIMS: The aim of this study was to evaluate the motor, sensory, functional, and
      head posture results of recession of the lateral rectus muscle contralateral to
      the involved eye in patients with exotropic Duane retraction syndrome (DRS) type
      3. METHODS: This was a retrospective, longitudinal, observational study of a
      consecutive clinical case series. Of the 11 patients with DRS type 3 operated on
      at a tertiary medical center from 1977 to 2012, 8 underwent recession of the
      lateral rectus muscle contralateral to the involved eye (with combined Y
      splitting of ipsilateral lateral rectus muscle in 3 of them). Full ophthalmic,
      orthoptic, and neurological examination was performed before and after surgery.
      Main outcome measures included intragroup changes in motor misalignment, abnormal
      head turn, ocular upshoot, and stereopsis. RESULTS: Mean patient age was 8.75+/
      3.1 years at surgery. Mean exodeviation for distance was -17.3+/-3.5 prism
      diopters (PD) preoperatively and -4.0+/-6.1 PD postoperatively; corresponding
      values for near were -23.1+/-7.2 PD and -5.9+/-8.7 PD. Motor deviation improved
      by 77% for distance (P=0.017) and 74.5% for near (P=0.01). In 7/8 patients, the
      postoperative residual exodeviation (distance and near) was <8.0 PD. There was an
      80% improvement in head turn, from 15.3+/-4 degrees  before surgery to 3.1+/-5.0
      degrees  after (P=0.01). Stereopsis improved significantly in 6/8 patients.
      Findings remained stable during follow-up (mean duration 35.9+/-50.8 months,
      range 5-132 months). CONCLUSIONS: Contralateral lateral rectus muscle recession
      appears to be a promising technique for the treatment of moderate unilateral DRS
      type 3, with patients showing significant motor and functional improvement and a
      decrease in head turn.

PMID- 24310236
TI  - Selective laser trabeculoplasty (SLT) vs other treatment modalities for glaucoma:
      systematic review.
AB  - PURPOSE: Systemic review to compare selective laser trabeculoplasty (SLT) to
      other glaucoma treatment options in terms of their intraocular pressure (IOP)
      lowering effect. METHODS: Searches of the following databases were performed:
      PubMed, Cochrane Central Register of Controlled Trials, Ovid, EMBASE,
      metaRegister of Controlled Trials, and ClinicalTrials.gov. Only randomised
      controlled trials (RCTs) published in peer-reviewed journals comparing SLT to
      other glaucoma treatment options were considered. The main outcome measure was
      the change in IOP from baseline. RESULTS: An initial search of PubMed identified
      23 RCTs with 17 meeting the inclusion criteria. Nine RCTs compared 180 degrees 
      SLT to 180 degrees  argon laser trabeculoplasty (ALT) and one trial compared 360
      degrees  SLT to 360 degrees  ALT, all reporting no difference in terms of IOP
      reduction from baseline. One RCT reported better outcomes with SLT at 1 year but
      this effect regressed at 2 years. Three trials compared 360 degrees  SLT to
      medical therapy and found no difference between the two treatment options. One
      trial found greater IOP reduction with latanoprost vs 90 degrees  and 180 degrees
      SLT, and greater IOP reduction with 180 degrees  and 360 degrees  SLT versus 90
      degrees  SLT, however no differences were found between 360 degrees  SLT versus
      latanoprost or 360 degrees  vs 180 degrees  SLT. Two trials compared 180 degrees 
      SLT to 360 degrees  SLT finding no difference in IOP reduction. Two trials
      compared 180 degrees  SLT to 90 degrees  SLT, one finding no significant
      difference and one finding greater IOP reduction with 180 degrees  SLT over 90
      degrees  SLT. One trial compared excimer laser trabeculotomy (ELT) to 180 degrees
      SLT, finding no differences in IOP reduction up to 3 months follow-up but
      greater IOP reduction with ELT at time intervals between 9 and 24 months. There
      were no RCTs identified that compared SLT to surgery. CONCLUSION: In terms of the
      IOP lowering effect, there is no difference between SLT and ALT. Three trials
      indicate no difference between 360 degrees  SLT and medical therapy, with one of
      the trials indicating greater IOP reduction with latanoprost over 90 degrees  and
      180 degrees  SLT. Three trials indicate no difference between 180 degrees  SLT
      and 360 degrees  SLT. It is inconclusive whether 90 degrees  is less efficacious
      than 180 degrees  SLT. One trial reports greater IOP reduction with ELT over 180
      degrees  SLT in the long term.

PMID- 24310237
TI  - Comment on: What is meso-zeaxanthin, and where does it come from?

PMID- 24310238
TI  - Visual acuity outcomes following surgery for idiopathic epiretinal membrane: an
      analysis of data from 2001 to 2011.
AB  - PURPOSE: Pars plana vitrectomy (PPV) is commonly used to remove the epiretinal
      membrane (ERM), but the timing of surgical intervention guided by visual acuity
      (VA) performance at presentation is uncertain. PATIENTS AND METHODS:
      Prospectively entered clinical data of 237 patients on an electronic patient
      record from 2001 to 2011 were analysed to determine visual outcomes, in
      particular in relation to pre-operative VA. RESULTS: The mean age of the patients
      was 68.8 years and 54.4% were female. Median follow-up was 0.55 years. The median
      pre-operative logMAR VA was 0.60 (SD 0.48-0.78, Snellen equivalent 6/36) and post
      operative VA was 0.30 (SD 0.18-0.60, 6/12, P<0.005). Pre-operative VA correlated
      with post-operative VA (linear R(2)=0.22, P<0.0001). In all, 69.6% of patients
      showed an improvement in VA, 15.2% showed no change, and the condition of 15.2%
      worsened. The number of patients with an improvement in logMAR VA of more than
      0.3 was greatest in those who had a pre-operative VA of 1.0 (6/60) or worse,
      followed by those in the range of 0.6-0.9 and then those with pre-operative VA of
      0.5 or better (P<0.001). The proportion of patients with visual improvement of
      logMAR VA of more than 0.3 increased statistically with progressing years
      (P=0.019). CONCLUSION: In conclusion, this study shows improvement in VA after
      PPV and ERM removal. Patients with better initial VA achieve higher levels of
      visual outcome but those with poorer pre-operative VA show a greater change in VA
      following ERM surgery. Results of surgery improved over the time period of the
      study.

PMID- 24310239
TI  - Optimising biometry for best outcomes in cataract surgery.
AB  - Biometry has become one of the most important steps in modern cataract surgery
      and, according to the Royal College of Ophthalmologists Cataract Surgery
      Guidelines, what matters most is achieving excellent results. This paper is aimed
      at the NHS cataract surgeon and intends to be a critical review of the recent
      literature on biometry for cataract surgery, summarising the evidence for current
      best practice standards and available practical strategies for improving outcomes
      for patients. With modern optical biometry for the majority of patients, informed
      formula choice and intraocular lens (IOL) constant optimisation outcomes of more
      than 90% within +/- 1 D and more than 60% within +/- 0.5 D of target are
      achievable. There are a number of strategies available to surgeons wishing to
      exceed these outcomes, the most promising of which are the use of strict
      tolerance IOLs and second eye prediction refinement.

PMID- 24310240
TI  - Response to Bernstein et al.

PMID- 24310241
TI  - Increased systemic oxidative stress in patients with keratoconus.
AB  - PURPOSE: To establish the effect of systemic oxidative stress on the pathogenesis
      of keratoconus by measuring serum total oxidant status (TOS) and total
      antioxidant status (TAS) in patients with keratoconus. METHODS: Twenty-five
      patients with keratoconus (keratoconus group) and 25 age-sex-matched healthy
      subjects (control group) were enrolled in the study. Exclusion criteria were
      smoking habit, history of any other corneal pathology, systemic disease or
      inflammation, and current antioxidant or anti-inflammatory therapies. All
      participants underwent a detailed ophthalmological examination and corneal
      topography. Serum samples were obtained from all participants. Oxidative stress
      markers (TAS and TOS) were measured using a commercial kit and oxidative stress
      index (OSI) was calculated. RESULTS: The study comprised 25 patients with
      keratoconus (mean age of 26.4+/-1.7 years) and 25 healthy control subjects (mean
      age of 26.6+/-1.7 years) (P>0.05). The serum TOS and OSI values were
      significantly higher in patients with keratoconus compared with those of the
      controls (P=0.036 and 0.037, respectively). However, serum TAS did not show
      significant difference between the keratoconus and control groups (P=0.497).
      CONCLUSIONS: The higher levels of serum oxidant status and OSI in patients with
      keratoconus suggest that systemic oxidative stress might be involved in the
      pathogenesis of keratoconus.

PMID- 24310242
TI  - Practical applications to modify and control the development of ametropia.
AB  - For many individuals, the developmental trend of lessening hyperopia from birth
      continues past emmetropia towards myopia during childhood. The global pattern for
      prevalence of refractive errors indicates that the prevalence of hyperopia is
      low; in contrast, the burden of myopia is on the rise because of rising
      prevalence and magnitude of myopia. This review highlights the need to lessen the
      global burden of myopia by intervening with the development and/or slowing the
      progression of myopia. Further, outcomes from human clinical trials of
      pharmaceutical, optical, and environmental approaches to control myopia will be
      summarised. Pharmaceutical treatments are effective in controlling eye growth but
      are associated with deleterious side effects. Optical strategies that induce
      myopic defocus at the retina such as peripheral defocus reducing lenses,
      simultaneous defocus lenses, bifocals, and orthokeratology as well as
      environmental influences such as increased outdoor activity show promise and
      provide a substantially risk-free environment in which to control eye growth. 

PMID- 24310244
TI  - Boron-trihalide-promoted regioselective ring-opening reactions of gem
      difluorocyclopropyl ketones.
AB  - Boron trihalide-promoted ring-opening reactions of gem-difluorocyclopropyl
      ketones to give the corresponding beta-trifluoromethyl ketones and beta
      halodifluoromethyl ketones were described. It was found that boron trihalides act
      as both Lewis acids and nucleophiles and the proximal bond prefers to cleave in
      this transformation. 

PMID- 24310243
TI  - Can improved intra- and inter-team communication reduce missed delirium?
AB  - To assess the prevalence and the team interaction in cases of missed delirium in
      acute care veterans coded as not having a diagnosis of delirium in admission or
      discharge notes. In this retrospective study, the records of 183 hospitalized
      veterans admitted to the emergency department (ED), medicine, surgery and
      psychiatry services and coded as not having a diagnosis of delirium were
      analyzed. Clinical notes of each case were examined using DSM IV TR criteria for
      delirium. Of the 52 cases assessed to have delirium, 5 cases had been miscoded as
      not having delirium. In the remaining 47 cases the diagnosis of delirium had been
      missed. The rates of undiagnosed delirium were ED 46/160, medicine 39/132,
      surgery 4/17, psychiatry 4/29 and consult liaison (CL) 0/9. Of the 5 cases of
      delirium identified by the CL service, 2 consult diagnoses were accepted and 3
      were rejected. Nursing notes had words suggesting delirium in 70.2 % of 47 cases
      compared to 41.3 and 43.6 % of the clinician case notes for these patients
      admitted to ED and medicine respectively. No delirium or cognitive screening
      scales were utilized in the work up of the 52 cases involving delirium. The study
      results suggest that continuing education by the CL service of all hospital
      personnel involved in patient care may improve the diagnosis of delirium. Also,
      increased clinician-nursing intra-team communication, in addition to careful
      scrutiny of the nursing and clinician notes may contribute to the reduced
      incidence of missed delirium. 

PMID- 24310245
TI  - Sex roles, personality, and intellectual abilities in adolescents.
AB  - The relationship between personality variables associated with sex roles and the
      cognitive variables of math and verbal ability was examined in three groups of
      adolescents. Masculinity and femininity of interests, behavioral traits, and
      values were examined using three inventories: the Femininity Scale from the
      California Psychological Inventory, the Bem Sex Role Inventory, and the Study of
      Values. Results indicate that there is some evidence for a positive relationship
      between masculine traits and values and math ability, and feminine traits and
      values and verbal skills (for both sexes). Certain traits indicative of maturity
      were found to be positively related to both high math and high verbal scores,
      while certain highly sex-typed traits and interests were found to be negatively
      related to both cognitive variables. A different relationship for males and
      females was found between high intellectual scores and indicators of self-concept
      and emotional well-being. The differing relationship between each of the three
      personality variables indicative of sex roles (e.g., interests, values, traits)
      and cognitive variables emphasizes the need to view masculinity and feminity, as
      well as "sex-role," as a complex combination of the many different aspects of sex
      roles as they exist in our society. 

PMID- 24310246
TI  - Adolescents-Too young to earn, too old to learn? Compulsory school attendance and
      intellectual development.
AB  - The desirability of secondary schooling has recently been challenged and a policy
      of allowing adolescents to enter work environments at an earlier age has been
      advocated. The potential losses in intellectual development that might result
      from early school leaving are assessed by reviewing evidence on the contribution
      of high schools and work to adolescents' intellectual development. The paper
      concludes that while students who have mastered basic skills may benefit from
      early work experience, students who have not achieved a level of intellectual
      development that would allow them to function as responsible adults should remain
      in an educational setting that is more likely to raise their skill level than a
      work environment. 

PMID- 24310247
TI  - Early work experience: A partial antidote for adolescent egocentrism.
AB  - One of the most important lessons a young person may learn from working is how to
      interact effectively with others. This potential outcome of work experience has
      received virtually no attention from proponents of the early integration of
      adolescents into the workplace. In this paper we suggest that working may
      contribute to the development of more advanced social understanding (i.e., social
      sensitivity, social insight, and effective social communication and manipulation)
      by requiring youngsters to (a) shift back and forth between diverse roles and (b)
      interact frequently with strangers. Illustrative material is presented from
      interviews with 100 working adolescents and their parents. 

PMID- 24310248
TI  - Depression and suicidal behavior among delinquent females.
AB  - Depressive symptomatology and suicidal behavior were evaluated in a multiethnic
      sample of 48 delinquent females through ratings on self-reports and probation
      officers' reports. Psychological functioning of the subjects was also evaluated
      through the Diagnostic Interview for Borderlines, the Rorschach, and the WAIS or
      WISC-R in order to identify delinquent personality patterns. Four personality
      patterns were identified: the borderline, the antisocial, the neurotic, and the
      socialized delinquent personalities. A chi-square analysis of the data
      demonstrated that level of depression and frequency of suicidal behavior were
      both significantly related to personality patterns. Level of depression was also
      significantly related to ethnicity, but not to socioeconomic status. The results
      have implications for assessment and treatment of delinquent females and also
      raise issues concerning the interaction of personality, cultural factors, and
      delinquent behavior which should be addressed in future research with larger,
      socioculturally diverse samples. 

PMID- 24310249
TI  - Correlates of adolescent pessimism: A study of the beck hopelessness scale.
AB  - This study examines correlates of the Beck Hopelessness Scale within an
      adolescent population. Consistent with studies employing adults as subjects,
      Hopelessness scores were found to be associated with depression and external
      locus of control. Additionally, a significant positive correlation was found
      between Hopelessness scores and an index of general maladjustment. The
      Hopelessness measure was, however, found to be unrelated to self-reported health
      status. 

PMID- 24310250
TI  - Young adults' evaluations of themselves and their parents as a function of family
      structure and disposition.
AB  - Young adults (N=349) were asked to evaluate, in a counterbalanced fashion, their
      mothers, fathers, and themselves. They also evaluated their families. Individuals
      from "happy" families were found to rate themselves significantly higher and
      their mothers somewhat higher than did their counterparts from "unhappy"
      families. Evaluations of fathers were not found to vary as a function of family
      happiness. Evaluations of fathers, but not mothers or subjects themselves, were
      found to vary significantly depending upon the structure of their family
      environments. Heider's attribution theory seems to be able to account for these
      varied findings. 

PMID- 24310251
TI  - Magnitude and direction of WISC-R verbal-performance IQ discrepancies among
      adjudicated male delinquents.
AB  - A field study is reported in which the discrepancy between verbal and nonverbal
      skills among 150 adjudicated male delinquents was assessed by the Wechsler
      Intelligence Scale for Children - Revised (WISC-R) and evaluated with respect to
      three interpretations of the observed differences. Alternative explanations were
      that the verbal-nonverbal disparity among delinquents (a) represented a group-by
      test interaction producing unusually large discrepancies, (b) was a function of
      intelligence level of the sample, and (c) was no more frequent among delinquents
      than nondelinquents when socioeconomic status (SES) was controlled. Results
      indicated that the WISC-R Verbal-Performance IQ discrepancy occurred reliably
      more often among delinquents than among controls. Individual differences within
      the two groups could be attributed neither to a group-by-test interaction, SES,
      or intelligence level. It was concluded that cognitive mediators of delinquent
      behavior differ mainly in degree form those of non-delinquents, and intellectual
      asymmetry is a concomitant variable significantly associated with delinquent
      behavior. 

PMID- 24310252
TI  - Possible involvement of DeltaNp63 downregulation in the invasion and metastasis
      of oral squamous cell carcinoma via induction of a mesenchymal phenotype.
AB  - Epithelial-to-mesenchymal transition (EMT), an essential developmental program,
      is involved in tumor progression. DeltaNp63, a homolog of p53, is associated with
      the EMT program, but the detailed mechanism remains to be elucidated. In this
      study, we investigated the role of DeltaNp63 in EMT during progression of oral
      squamous cell carcinoma (OSCC). Five OSCC cell lines and specimens from 78
      patients with OSCC were used. The expressions of DeltaNp63, p63alpha, p63beta and
      epithelial markers (cytokeratins 5 and 14) was detected in the OSCC cells, but
      not in SQUU-B cells (high metastatic potential). E-cadherin was expressed in all
      OSCC cells. Mesenchymal markers were strongly expressed in the SQUU-B cells.
      Knockdown of endogenous DeltaNp63 in HSC-2 cells induced morphological changes to
      the spindle shape, decreased the expression of epithelial markers, increased the
      expression of mesenchymal markers, increased migration and reduced proliferation.
      By contrast, SQUU-B cells overexpressing DeltaNp63beta showed changed their
      morphology from stromal cell-like to epithelial cells. However, E-cadherin
      expression was not affected by DeltaNp63 knockdown or overexpression.
      Immunohistochemical staining revealed that cancer cells expressing vimentin were
      found at the invasive front in the OSCC specimens. The intensity of DeltaNp63
      expression was also decreased in these cells. Interestingly, the vimentin
      positivity or decreased intensity of DeltaNp63 was positively associated with
      metastases and poor prognosis in the OSCC patients. These results indicated that
      DeltaNp63 downregulation in cancer cells induces a mesenchymal phenotype that is
      related to tumor progression of OSCC.

PMID- 24310253
TI  - Kinetic and mechanistic studies of 1,3-bis(2-pyridylimino)isoindolate Pt(II)
      derivatives. Experimental and new computational approach.
AB  - The rate of substitution of the chloride ligand by three bio-relevant
      nucleophiles, thiourea (Tu), N,N-dimethylthiourea (Dmtu) and N,N,N,N
      tetramethylthiourea (Tmtu), in the complexes: 1,3-bis(2-pyridylimino)isoindoline
      platinum(II) chloride (Pt2), 1,3-bis(2-pyridylimino)benz(f)isoindoline
      platinum(II) chloride (Pt3) and 1,3-bis(1-isoquinolylimino)isoindoline
      platinum(II) complex (Pt4) was investigated under pseudo first-order conditions
      as a function of concentration and temperature using stopped-flow and UV-Visible
      spectrophotometry. Computational modeled data of bis(pyridylimino)3,4-pyrrolate
      platinum(II) chloride (Pt1) were incorporated in the study for comparison. The
      observed pseudo first-order rate constants for substitution reactions obey the
      rate law kobs = k2[Nu]. High negative activation entropies and second-order
      kinetics for the displacement reactions all support an associative mode of
      activation. The reactivity is dependent on stabilization of the LUMO energy and
      inversely proportional to the number of phenyl rings added irrespective of the
      site of attachment. The electron density on the ligand moiety plays a significant
      role in the substitution behavior of the platinum(II) complexes, as supported by
      DFT descriptors {electrophilicity index (omega) and chemical hardness (eta)}.

PMID- 24310254
TI  - Host-specific nodulation is encoded on a 14kb DNA fragment in Rhizobium trifolii.
AB  - The Rhizobium trifolii genes necessary for nodule induction and development have
      been isolated on a 14.0kb fragment of symbiotic (Sym) plasmid DNA. When cloned
      into a broad-host-range plasmid vector, these sequences confer a clover
      nodulation phenotype on a derivative of R. trifolii which has been cured of its
      endogenous Sym plasmid. Furthermore, these sequences encode both host specificity
      and nodulation functions since they confer the ability to recognize and nodulate
      clover plants on Agrobacterium and a fast-growing cowpea Rhizobium. This
      indicates that the bacterial genes essential for the initial, highly-specific
      interaction with plants are closely linked. 

PMID- 24310255
TI  - DNA sequences for the Zea mays tRNA genes tV-UAC and tS-UGA: tV-UAC contains a
      large intron.
AB  - The chloroplast genome contains genes for a large and probably complete set of
      tRNAs. These genes are unique in sharing attributes of both nuclear and bacterial
      tRNA genes. Two chloroplast tRNA genes from Zea mays are described here. tV-UAC,
      encoding a valine tRNA with the anticodon UAC, contains a 603 bp intron and is
      highly homologous, both in coding regions and in the intron, to the analogous
      gene from tobacco described by Deno et al. (Nucleic Acids Res 10:7511-7520,
      1982). It is located near the gene for the beta and epsilon subunits of the CF1
      complex. (Krebbers et al.: Nucleic Acids Res 10:4985-5002, 1982). The gene tS
      UGA, encoding a serine tRNA with the anticodon UGA, is located 41 kbp 3' to tV
      UAC. Both genes contain promoter-like sequences in their 5' flanking regions. 

PMID- 24310256
TI  - Appearance and accumulation of nodulin mRNAs and their relationship to the
      effectiveness of root nodules.
AB  - Cloned cDNAs corresponding to mRNAs which accumulate in nitrogen-fixing root
      nodules of soybean (nodulin mRNAs) were used as probes to investigate the sizes,
      sequence relationships, tissue specificities and developmental accumulations of
      individual nodulin mRNA sequences. Northern blot analysis indicated that the
      NodB, NodC and NodD mRNA sequences are 1 150, 770, and 3 150 nucleotides long,
      respectively, which is consistent with the previously determined sizes of the
      hybrid-selected translation products (27 000, 24 000 and 100 000 MW,
      respectively). The NodA clones pNodA15 and pNodA25 hybridized to two mRNAs of
      lengths 1 600 and 1 100 nucleotides, indicating that they contain significant
      sequence homologies. However, increasing the hybridization stringency showed that
      the pNodA15 clone encodes the 1 600 nucleotide mRNA corresponding to the major
      NodA hybrid-selected translation product (44 000 MW) while pNodA25 encodes an
      mRNA of 1 100 nucleotides. The latter probably corresponds to one of two smaller
      (23 500 and 24 500 MW) in vitro translation products. RNA dot-blot hybridizations
      indicated that nodulin and leghemoglobin mRNAs began to appear and accumulate in
      Rhizobium infected root tissue very early (day 3 to 5) and reached fully induced
      levels by day 11. This accumulation was specific for nodule tissue (except for
      the NodD sequence) and preceded the accumulation of nitrogen fixation activity.
      Nodules produced by different effective Rhizobium strains accumulated similar
      levels of leghemoglobin and nodulin mRNAs while ineffective strains had a
      pleiotropic affect. While one ineffective strain (61A24) gave reduced levels of
      all these mRNAs, the other (SM5) gave levels which were nearly normal by the time
      nitrogen fixation activity should have reached its maximal level (day 17). Thus,
      leghemoglobin and nodulin genes are switched on soon after infection, prior to
      nodule morphogenesis, and the switch occurs prior to and is independent of
      nitrogen fixation activity. 

PMID- 24310257
TI  - Mapping of transfer RNA genes on tobacco chloroplast DNA.
AB  - Tobacco chloroplast tRNAs have been purified by two-dimensional polyacrylamide
      gel electrophoresis, identified by aminoacylation, labelled at their 3'-end and
      hybridized to tobacco chloroplast DNA restriction fragments, in order to
      establish a tRNA gene map. These hybridization studies have revealed the
      localization of at least seven genes in each inverted repeat region, a minimum of
      22 tRNA genes in the large single copy region and one tRNA gene in the small
      single copy region. Comparison of the tobacco chloroplast tRNA gene map to that
      of maize shows many similarities, but also some differences suggesting that DNA
      sequence rearrangements have occurred in the chloroplast genome during evolution.

PMID- 24310258
TI  - Localization of the replicase recognition site within brome mosaic virus RNA by
      hybrid-arrested RNA synthesis.
AB  - 3' terminal fragments of BMV RNA as short as 153 bases in length serve as
      efficient templates in vitro for BMV-specific RNA polymerase. Template activity
      of such fragments or of native BMV RNA is abolished when cDNA fragments as short
      as 39 bases are hybridized to their 3' termini. Hybridization of cDNa fragments
      to regions of BMV RNA 200 or more bases distal to the 3' end has no discernible
      effect on initiation and little effect on elongation. We conclude that BMV RNA
      polymerase initiates binding with an RNA template through a mechanism mediated by
      the tRNA-like 3' end of BMV RNA, requiring at least some of the last 39, but no
      more than the last 153 bases. 

PMID- 24310260
TI  - [Structural quality in inpatient medical rehab and prevention centers for
      mothers, fathers and children].

PMID- 24310259
TI  - Comparative analysis of physical stress responses in soybean seedlings using
      cloned heat shock cDNAs.
AB  - Soybean seedlings were subjected to a wide range of physical (abiotic) or
      environmental stresses. Cloned cDNAs to heat shock (hs)-induced mRNAs were used
      to assess whether these diverse stresses induced the accumulation of poly(A)RNAs
      in common with those induced by hs. Northern blot hybridization analyses
      indicated that a wide range of stress agents lead to the accumulation of
      detectable levels of several of the hs-induced poly(A)RNAs; the relative
      concentration of those RNAs 'induced' by the wide range of stress agents (e.g.
      water stress, salt stress, anaerobiosis, high concentrations of hormones, etc.),
      was generally in the order of 100-fold lower than that induced by hs. There are
      two notable exceptions to that pattern of response to the stress agents. First,
      arsenite treatment resulted in accumulation of the 'hs poly(A)RNAs' to levels
      similar to those induced by hs. Cadmium also induced a somewhat normal spectrum
      of the 'hs poly(A)RNAs', but generally lower levels accumulated than in hs- and
      arsenite0treated tissues. Second, one set of poly(A)RNAs which are present at low
      and variable levels in control (non-stressed tissue) tissue, and which are
      increased some 5- to 10-fold by hs, increased in relative concentration in
      response to a wide range of the stress agents similarly to the response to hs.
      The physiological significance of the accumulation of this set of poly(A)RNAs
      (which translate into four electrophoretically different 27 kd proteins) is not
      known, but they certainly seem to serve as a monitor (or barometer) of
      physiological stress conditions. Cadmium treatment results in the accumulation of
      those same poly(A)RNAs and an additional band of higher molecular weight
      poly(A)RNA homologous to the same hs cDNA clone (clone pCE 54). Ethylene seems to
      have no obvious causal relationship to the hs response, even though hs-treated
      seedlings display some symptoms similar to those exhibited by ethylene-treated
      seedlings. 

PMID- 24310261
TI  - [How to do forensic socio-medical assessments in mental disorders].

PMID- 24310262
TI  - [Letter to the editor: Rehabilitation after hip and knee arthroplasty. Die
      rehabilitation 2013; 52: 202-212].

PMID- 24310263
TI  - [Rehabilitation research in North Rhine Westphalia--outcomes of the future
      workshop of the NRW Research Association for Rehabilitation Sciences June 28,
      2012 in Bielefeld and October 19, 2012 in Munster (Westphalia)].

PMID- 24310266
TI  - Multimodal imaging in persistent placoid maculopathy.
AB  - IMPORTANCE: Persistent placoid maculopathy (PPM) is a rare clinical entity with
      features that superficially resemble acute posterior multifocal placoid pigment
      epitheliopathy (APMPPE) and macular serpiginous choroidopathy. It is important to
      differentiate PPM from APMPPE because both conditions may appear similar at
      presentation. OBJECTIVE: To investigate the short-term and long-term retinal
      changes in patients with PPM using spectral domain optical coherence tomography
      (SD-OCT), indocyanine green angiography (ICG-A), fluorescein angiography (FA),
      and fundus autofluorescence (FAF). DESIGN, SETTING, AND PARTICIPANTS: We
      performed a retrospective medical record review in 5 patients diagnosed as having
      PPM at tertiary retinal practices. MAIN OUTCOMES AND MEASURES: Findings on SD
      OCT, FA, digital FAF, and ICG-A images. RESULTS: Patients presented within 2
      weeks of subjective symptoms. Mean best-corrected visual acuity was 20/144
      (range, 20/25-20/400). At presentation, all but 1 patient had bilateral macular
      lesions. Four eyes developed extramacular lesions during follow-up. On SD-OCT,
      the acute placoid lesions revealed hyperreflectivity of the outer nuclear layer;
      disruption of the external limiting membrane, ellipsoid layer, and
      interdigitation zone; and, in some patients, hyporeflective spaces at the level
      of absent outer segments. On follow-up, lesions revealed either partial or
      complete restoration of the outer retinal architecture or they progressed to
      atrophy. On FA, all placoid lesions were hypofluorescent in early frames and
      hyperfluorescent in late frames. In the acute stage, ICG-A revealed sharply
      delineated dense hypofluorescent lesions, which persisted on late frames in all
      patients. Hypofluorescent lesions faded completely or partially after resolution
      of the placoid lesions on SD-OCT and clinical examination. Variability was seen
      on the FAF patterns; most lesions were hyperautofluorescent, except in 1 patient,
      in whom they were hypoautofluorescent. Bilateral choroidal neovascularization
      developed in only 1 patient. The mean follow-up was 28 weeks (range, 2-92 weeks).
      On the final follow-up visit, mean best-corrected visual acuity was 20/125
      (range, 20/25-20/400). CONCLUSIONS AND RELEVANCE: On SD-OCT, acute retinal
      changes in PPM involve the outer nuclear layer, external limiting membrane,
      ellipsoid layer, and interdigitation zone. The retinal pigment epithelium and
      choroid are involved in severely affected patients. The variable extent of
      retinal pigment epithelium involvement was reflected in variable FAF findings. We
      discuss clinical features that differentiate this entity from other white spots,
      including acute placoid multifocal pigment epitheliopathy. Additional long-term
      imaging studies are needed to further clarify the exact location and pathogenesis
      of this rare disease.

PMID- 24310267
TI  - Faecal microbiota composition and host-microbe cross-talk following
      gastroenteritis and in postinfectious irritable bowel syndrome.
AB  - BACKGROUND: About 10% of patients with IBS report the start of the syndrome after
      infectious enteritis. The clinical features of postinfectious IBS (PI-IBS)
      resemble those of diarrhoea-predominant IBS (IBS-D). While altered faecal
      microbiota has been identified in other IBS subtypes, composition of the
      microbiota in patients with PI-IBS remains uncharacterised. OBJECTIVE: To
      characterise the microbial composition of patients with PI-IBS, and to examine
      the associations between the faecal microbiota and a patient's clinical features.
      DESIGN: Using a phylogenetic microarray and selected qPCR assays, we analysed
      differences in the faecal microbiota of 57 subjects from five study groups:
      patients with diagnosed PI-IBS, patients who 6 months after gastroenteritis had
      either persisting bowel dysfunction or no IBS symptoms, benchmarked against
      patients with IBS-D and healthy controls. In addition, the associations between
      the faecal microbiota and health were investigated by correlating the microbial
      profiles to immunological markers, quality of life indicators and host gene
      expression in rectal biopsies. RESULTS: Microbiota analysis revealed a bacterial
      profile of 27 genus-like groups, providing an Index of Microbial Dysbiosis (IMD),
      which significantly separated patient groups and controls. Within this profile,
      several members of Bacteroidetes phylum were increased 12-fold in patients, while
      healthy controls had 35-fold more uncultured Clostridia. We showed correlations
      between the IMD and expression of several host gene pathways, including amino
      acid synthesis, cell junction integrity and inflammatory response, suggesting an
      impaired epithelial barrier function in IBS. CONCLUSIONS: The faecal microbiota
      of patients with PI-IBS differs from that of healthy controls and resembles that
      of patients with IBS-D, suggesting a common pathophysiology. Moreover, our
      analysis suggests a variety of host-microbe associations that may underlie
      intestinal symptoms, initiated by gastroenteritis.

PMID- 24310268
TI  - Electroantennogram responses of grape borerXylotrechus pyrrhoderus bates
      (Coleoptera: Cerambycidae) to its male sex pheromone components.
AB  - Electroantennograms were recorded from the grape borerXylotrechus pyrrhoderus in
      response to serial dilutions of male sex pheromone components, (2S,3S)-octanediol
      and (2S)-hydroxy-3-octanone, and to 100 MUg of their optical isomers and host
      plant substances. Female antennae always responded more strongly than male
      antennae. Antennae of both sexes were highly sensitive to (2S)-hydroxy-3
      octanone. F/M ratio (female to male EAG value) was greater for male sex pheromone
      components, especially (2S,3S)-octanediol, and their optical isomers than plant
      substances. Antennal sensitivity to optical isomers (2R,3R-octanediol and 2S,3R
      octanediol) was lower than true pheromone components. 

PMID- 24310269
TI  - Three European corn borer populations in New York based on sex pheromones and
      voltinism.
AB  - Pheromone blend analyses of glands from individual female European corn
      borers,Ostrinia nubilalis (Hubner), from field-collected larvae or pupae
      associated with bivoltine flights in June and August and a univoltine flight in
      July have shown that: (1) a site in western New York has a bivoltine biotype
      utilizing (Z)-11-tetradecenyl acetate as its primary pheromone component
      (designatedZ), (2) two sites in central New York have mixed populations
      consisting of a bivoltine biotype utilizing theE pheromone isomer (designatedE)
      and a univoltine biotype utilizingZ, and (3) one site in central New York was
      found to have only the univoltineZ biotype. The combinations of voltine biotypes
      and pheromone strains found in New York support the existence of three European
      corn borer populations designated bivoltineE, bivoltineZ, and univoltineZ. 

PMID- 24310270
TI  - Orientation behavior of second-instar larvae of eastern spruce
      budwormChoristoneura fumiferana (Clem.) (Lepidoptera: Tortricidae) in a y-type
      olfactometer.
AB  - A two-choice, wind-tunnel olfactometer was designed and contructed to determine
      whether second-instar eastern spruce budworm larvae,Christoneura fumiferana
      (Clem.), could detect and discriminate among host-plant volatiles. Volatiles of
      current year's growth ofPicea glauca were preferred over those ofP. rubens, P.
      mariana, or air.Abies balsamea was preferred overP. mariana or air.P. rubens
      andP. mariana were both preferred over air. Two-year-old growth ofP. glauca, A.
      balsamea, P. rubens, andP. mariana were all preferred over air. Current year's
      growth of these host evergreen species was usually preferred over former year's
      growth of the same species in each case. 

PMID- 24310271
TI  - Inhibition of Cyanogenesis by tannins.
AB  - During isolation of two biosynthetic types of cyanogenic glycosides fromCarica
      papaya, weak cyanide tests were obtained from initial fractions. Upon final
      purification, strongly positive cyanide tests were obtained. Pretreatment of
      extracts to remove polyphenolics alleviated inhibition of cyanogenesis, which led
      us to suspect that tannins were inhibitory agents. Qualitative and quantitative
      measures of inhibition were made using standard cyanogenic glycosides and
      polyphenolics. Cyanogenesis was inhibited quantitatively when condensed tannins
      (quebracho, wattle, and chestnut), or hydrolyzable tannin (tannic acid) were
      added. When tannins were precipitated from the reaction mixture, cyanide tests
      proceeded optimally. These results stress the need to interpret negative cyanide
      tests with care and indicate possible ecological synergisms between plant
      defensive chemicals. 

PMID- 24310272
TI  - Sticky secretion from two pairs of defensive glands of rove beetleDeleaster
      dichrous (Grav.) (Coleoptera: Staphylinidae) : Gland morphology, chemical
      constituents, defensive functions, and chemotaxonomy.
AB  - The phylogenetically primitive rove beetleDeleaster dichrous (Grav.) (Oxytelinae)
      has been shown for the first time to possess two pairs of neighboring abdominal
      glands which are depleted simultaneously on molestation. The morphology of these
      glands is described. The defensive constituents of theDeleaster glands were
      elucidated directly from the mixtures by gas chromatographic-mass spectroscopic
      methods and microchemical reactions. The paired whitish glands secrete iridodial,
      which polymerizes on exposure to air to form an adhesive that probably deters
      small predatory arthropods. The red gland system ofD. dichrous contains the
      toxicp-toluquinone and a variety of isopropyl andsec-butyl esters. Artificial
      quinoid ester mixtures simulating the secretion ofD. dichrous showed only weak
      effects on mortality ofLucilia larvae in comparison with more effective
      secretions of phyiogenetically derived Oxytelinae. The secretion of the primitive
      genusDeleaster is characterized chemotaxonomically by beta, gamma-unsaturated C12
      acids and esters, which are postulated as precursors for the characteristic
      defensive compounds of the derived species, thus indicating a clear evolutionary
      trend at the micromolecular level. 

PMID- 24310273
TI  - Lack of effect of (-)-disparlure on orientation towards (+)-disparlure source in
      walking and flying gypsy moth males.
AB  - In order to reveal the mechanism by which an inhibitory substance acts,
      orientation towards an attractant and attractant-inhibitor mixed source was
      studied in male gypsy moths. The inhibitory (-)-disparlure had no effect on the
      moth's ability to locate the attractant (+)-disparlure source while walking or
      flying in a laminar airstream. This absence of any inhibitory effect indicates
      that only very specific components of the moth's orientation behavior, as
      discussed, are distributed by the (-)-disparlure. 

PMID- 24310274
TI  - Volatiles from mandibular glands of male beewolves (Hymenoptera:
      Sphecidae,Philanthus) and their possible roles.
AB  - Observations of wasp behavior indicate that male beewolves,Philanthus basilaris
      andP. bicinctus apply a "marking pheromone" to the leaves and stems of plants
      within their territories. We now provide direct evidence for the presence of
      volatile chemicals in the paired mandibular glands of the males, provide
      preliminary identification of these volatiles, and show that all of the volatile
      chemicals in the mandibular glands are present on freshly marked plant surfaces
      but are absent from unmarked plants. Pyrazines, which have been reported in other
      species of aculeate wasps including the EuropeanPhilanthus triangulum, were not
      found inP. basilaris orP. bicinctus. 

PMID- 24310275
TI  - Use of predator odors as repellents to reduce feeding damage by herbivores : I.
      Snowshoe hares (Lepus americanus).
AB  - The effectiveness of predator odors (fecal, urine, and anal scent gland) in
      suppressing feeding damage by snowshoe hares was investigated in pen bioassays at
      the University of British Columbia Research Forest, Maple Ridge, British
      Columbia, Canada. A total of 28 bioassay trials tested the effects of these odors
      on hare consumption of willow browse and coniferous seedlings. Lynx and bobcat
      feces, weasel anal gland secretion, and lynx, bobcat, wolf, coyote, fox, and
      wolverine urines resulted in the most effective suppression of hare feeding
      damage. Novel odors of domestic dog urine and 2-methylbutyric acid did not reduce
      feeding. A field bioassay with lodgepole pine seedlings and weasel scent provided
      significant results comparable to the pen bioassays. The short-term (up to seven
      days) effectiveness of these treatments was more likely due to evaporative loss
      of the active repellent components of a given odor than habituation of hares to
      the stimulus. Predator odors as repellents have a biological basis compared with
      the anthropomorphic origins of commercial repellents. When encapsulated in
      weather-proof controlled-release devices, these odors could provide long-term
      protection for forestry plantations and agricultural crops which experience
      hare/rabbit feeding damage. 

PMID- 24310276
TI  - Use of predator odors as repellents to reduce feeding damage by herbivores : II.
      Black-tailed deer (Odocoileus hemionus columbianus).
AB  - The effectiveness of predator odors (fecal and urine) in suppressing feeding
      damage by black-tailed deer was investigated in pen bioassays at the University
      of British Columbia Research Forest, Maple Ridge, British Columbia, Canada. A
      total of eight bioassay trials tested the effects of these odors on deer
      consumption of salal leaves and coniferous seedlings. Cougar, coyote,and wolf
      feces as well as coyote, wolf, fox, wolverine, lynx, and bobcat urines provided
      the most effective suppression of deer feeding damage. Novel odors of ammonia and
      human urine did not reduce feeding. Predator fecal odor formulations in direct
      foliar application, adhesive application, and in plastic vials were all effective
      in suppressing deer feeding. Of all urines tested, coyote provided the most
      consistent suppression of deer browsing on salal. Deer consumed significantly
      more untreated Douglas fir and western red cedar seedlings than those protected
      by coyote urine odor. The active repellent components of predator odors which
      suppress deer feeding may be suitable for encapsulation in controlled-release
      devices which could provide long-term protection for forest and agricultural
      crops. 

PMID- 24310277
TI  - Juglone concentration in soil beneath black walnut interplanted with nitrogen
      fixing species.
AB  - Juglone concentration was measured in soils collected under a 14-year-old black
      walnut (Juglans nigra L.) plantation containing plots of pure walnut and of
      walnut mixed with either autumn-olive (Elaeagnus umbellata Thunb.) or European
      black alder (Alnus glutinosa (L.) Gaertn.). Juglone concentrations declined with
      soil depth and distance from the walnut tree. Concentrations in autumn-olive
      walnut plots were statistically lower than concentrations in European black alder
      walnut or pure walnut plots. The concentration of juglone in soil in European
      black alder-walnut plots was apparently sufficient to cause the onset of black
      alder mortality. 

PMID- 24310278
TI  - Monoterpene oviposition stimulants ofDioryctria amatella in volatiles from
      fusiform rust galls and second-year loblolly pine cones.
AB  - Volatiles collected on Poropak Q from fusiform rust galls (Cronartium quercuum F.
      sp.fusiforme) of loblolly pine for 3 hr were better ovi-position stimulants
      forDioryctria amatella (Hulst) females than extracts of 8-hr collections. GLC
      analysis of these extracts showed no major differences in relative monoterpene
      composition, although 8-hr collections contained an unidentified compound not
      detected in the 3-hr collections. Comparison of volatiles from second-year
      loblolly pine cones with those from fusiform galls showed that both containeddl
      alpha-pinene, (-)-beta-pinene, myrcene, and (+)-limonene. Camphene was found in
      galls only, and relatively large quantities of beta-phellandrene were identified
      only from cones. The five major monoterpenes found in the two host substrates
      were tested in an oviposition bioassay. Eighteen trials using different
      combinations of these terpenes showed that the combination of alpha-pinene,
      myrcene, and limonene was as attractive toD. amatella females as all other
      terpene combinations, including turpentine. 

PMID- 24310279
TI  - Metabolic activity measured on PET/CT correlates with clinical outcomes in
      patients with limb and girdle sarcomas.
AB  - OBJECTIVE: To explore the relationship between metabolic activity and outcome in
      patients with extremity sarcomas. METHODS: Between June 2004 and December 2011,
      120 patients with newly diagnosed limb and girdle sarcomas underwent FDG-PET/CT
      for disease staging prior to curative intent treatment. The maximum standardized
      uptake value (SUV(max)) was measured for each primary tumor and correlated with
      outcome. Progression-free survival and overall survival (OS) were analyzed using
      the Kaplan-Meier method. RESULTS: Soft-tissue sarcomas were more frequent (68%)
      than bone (27%) or cartilage (5%) tumors. Median follow-up was 33.2 months. 51%
      of patients progressed during the follow-up interval and 38% died. SUV(max) was
      dichotomized with a cut-point of 10.3. Patients with SUV(max) < 10.3 had better
      DFS and OS compared with patients with SUV(max) >= 10.3 (P < 0.001 and P < 0.001,
      respectively [log-rank test]). Multivariate analysis confirmed that even after
      adjusting for age, sex, site, tumor type (bone vs. soft-tissue), grade, and
      stage; an SUV(max) >= 10.3 correlated with a twofold risk of progression and 2.4
      times greater risk of death (hazard ratio [HR] 2.0, 95% CI, 1.1-3.7, and HR, 2.4,
      95% CI, 1.1-4.9). CONCLUSION: SUV(max) is an independent adverse prognostic
      factor for both progression and OS in patients with extremity sarcomas.

PMID- 24310281
TI  - Secondary health conditions in individuals with spinal cord injury: a sign of
      premature ageing?

PMID- 24310280
TI  - A comparison of coronary CTA and stress testing using high-efficiency SPECT MPI
      for the evaluation of chest pain in the emergency department.
AB  - BACKGROUND: Recent studies have compared CTA to stress testing and MPI using
      older Na-I SPECT cameras and traditional rest-stress protocols, but are limited
      by often using optimized CTA protocols but suboptimal MPI methodology. We
      compared CTA to stress testing with modern SPECT MPI using high-efficiency CZT
      cameras and stress-first protocols in an ED population. METHODS: In a
      retrospective, non-randomized study, all patients who underwent CTA or stress
      testing (ETT or Tc-99m sestamibi SPECT MPI) as part of their ED assessment in
      2010-2011 driven by ED attending preference and equipment availability were
      evaluated for their disposition from the ED (admission vs discharge, length of
      time to disposition), subsequent visits to the ED and diagnostic testing (within
      3 months), and radiation exposure. CTA was performed using a 64-slice scanner (GE
      Lightspeed VCT) and MPI was performed using a CZT SPECT camera (GE Discovery
      530c). Data were obtained from prospectively acquired electronic medical records
      and effective doses were calculated from published conversion factors. A
      propensity-matched analysis was also used to compare outcomes in the two groups.
      RESULTS: A total of 1,458 patients underwent testing in the ED with 192 CTAs and
      1,266 stress tests (327 ETTs and 939 MPIs). The CTA patients were a lower-risk
      cohort based on age, risk factors, and known heart disease. A statistically
      similar proportion of patients was discharged directly from the ED in the stress
      testing group (82% vs 73%, P = .27), but their time to disposition was longer
      (11.0 +/- 5 vs 20.5 +/- 7 hours, P < .0001). There was no significant difference
      in cardiac return visits to the ED (5.7% CTA vs 4.3% stress testing, P = .50),
      but more patients had follow-up studies in the CTA cohort compared to stress
      testing (14% vs 7%, P = .001). The mean effective dose of 12.6 +/- 8.6 mSv for
      the CTA group was higher (P < .0001) than 5.0 +/- 4.1 mSv for the stress testing
      group (ETT and MPI). A propensity score-matched cohort showed similar results to
      the entire cohort. CONCLUSIONS: Stress testing with ETT, high-efficiency SPECT
      MPI, and stress-only protocols had a significantly lower patient radiation dose
      and less follow-up diagnostic testing than CTA with similar cardiac return
      visits. CTA had a shorter time to disposition, but there was a trend toward more
      revascularization than with stress testing.

PMID- 24310282
TI  - Solute accumulation differs in the vacuoles and apoplast of ripening grape
      berries.
AB  - Phloem unloading is thought to switch from a symplastic route to an apoplastic
      route at the beginning of ripening in grape berries and some other fleshy fruits.
      However, it is unclear whether different solutes accumulate in both the mesocarp
      vacuoles and the apoplast. We modified a method developed for tomato fruit to
      extract apoplastic sap from grape berries and measured the changes in apoplastic
      and vacuolar pH, soluble sugars, organic acids, and potassium in ripening berries
      of Vitis vinifera 'Merlot' and V. labruscana 'Concord'. Solute accumulation
      varied by genotype, compartment, and chemical species. The apoplast pH was
      substantially higher than the vacuolar pH, especially in Merlot (approximately
      two units). However, the vacuole-apoplast proton gradient declined during
      ripening and in Merlot, but not in Concord, collapsed entirely at maturity.
      Hexoses accumulated in both the vacuoles and apoplast but at different rates.
      Organic acids, especially malate, declined much more in the vacuoles than in the
      apoplast. Potassium accumulated in the vacuoles and apoplast of Merlot. In
      Concord, by contrast, potassium increased in the vacuoles but decreased in the
      apoplast. These results suggest that solutes in the fruit apoplast are tightly
      regulated and under developmental control. 

PMID- 24310284
TI  - Pollen tube expression of pseudo-self-compatibility (PSC) inPetunia hybrida.
AB  - AnS 1.1 self-incompatible (SI) petunia plant which showed atypical seed set was
      found in an I7 population. This plant showed a strong SI reaction when selfed but
      produced varying amounts of seed when used as the seed parent in crosses with
      unrelated individuals homozygous for the sameS allele. Reciprocal crosses yielded
      no seed indicating that the reaction was a stylar response. Self seed obtained by
      high temperature treatments produced 18 plants, all of which exhibited the
      parental characteristics, the ability to reject self pollen but accept, to
      varying degrees, pollen bearing the sameS allele from unrelated plants. Several
      petunias homozygous forS 1, and exhibiting various levels of PSC as determined by
      self seed set, progeny tests and temperature treatments, were used as pollen
      parents. The mean seed set of these crosses produced a ranking of the pollen
      parents which reflected the PSC levels obtained by other methods. The behavior of
      the F1 and F2 populations suggests that the pollen discriminating ability may be
      a simply inherited, dominant character in these plants. The styles of these
      unusual petunias illustrate the participation of the pollen tube in determining
      PSC. 

PMID- 24310283
TI  - Sternal development in the pediatric population: evaluation using computed
      tomography.
AB  - BACKGROUND: The normal development of the sternum using CT imaging is not known.
      OBJECTIVE: To describe the normal development of the sternum in children on chest
      CT imaging. MATERIALS AND METHODS: CT imaging of 300 patients (150 male, 150
      female), mean age: 4.97 years (range: 0.01-9.9 years), were evaluated
      retrospectively. The presence and number of ossification centers in the
      manubrium, each individual mesosternal segment and the xiphoid were reviewed.
      Additionally, the vertical and horizontal fusion between ossification centers was
      evaluated. Differences among age and gender were calculated. Descriptive
      statistics, analysis of variances (ANOVA), chi-square and Fisher exact tests were
      performed for statistical analysis. RESULTS: Manubrium: A single ossification
      center was seen in 88% of cases and two or three ossification centers were seen
      in 12%. More manubrial ossification centers were correlated to a younger age (P <
      0.001, R = -0.2). Mesosternum: Majority of patients had a single ossification
      center in the first segment (85%). The majority of patients had double
      ossification centers in the second and third segments (51% and 64%,
      respectively). No ossification center was seen in the fourth segment in 38% of
      patients. No significant difference among the age of vertical ossification
      between mesosternal segments was found. (ANOVA; P > 0.05). Xiphoid: Absence was
      seen in 67% of the patients. Bifid xiphoid was seen in 1% of the patients.
      CONCLUSION: The normal development of the different components of the sternum is
      a process with wide variation among children. The large variability of
      mesosternal ossification center types should not be confused with pathology.

PMID- 24310286
TI  - Genetics of incompatibility inCorylus avellana L.
AB  - Diallele crosses of sibs and parents of 3 parental combinations demonstrated
      sporophytic type of incompatibility inCorylus avellana L. One gene with multiple
      alleles was indicated. All 6 alleles present in the 4 parental cultivars and in
      their progeny exhibited dominance in pollen and independent action in the pistil.
      Individuals homozygous for S-alleles appeared in progeny of parents having one
      allele in common. Reciprocal differences occurred in some crosses. The stigmatic
      surface is the site of the incompatibility reaction. Incompatible pollen
      germinated abundantly but failed to penetrate into the stigma cells. 

PMID- 24310285
TI  - The allotetraploidization of maize : Part 1: The physical basis - differential
      pairing affinity.
AB  - Allotetraploidization is the creation of artificial allotetraploids.
      Allotetraploidization of maize can be achieved by restructuring a maize genome so
      that its chromosomes will not pair with those of the normal maize genome. The
      restructuring can be done by concentrating induced or naturally occurring visible
      and cryptic chromosome aberrations and qualitatively different genetic material
      into a single line by a recurrent selection type of breeding program. The basis
      of allotetraploidization is the presence of differential pairing affinity between
      normal and restructured chromosomes. Experiments demonstrate that differential
      pairing affinity factors occur naturally in exotic races and in standard corn
      belt inbred lines and that they may be readily induced by X-irradiation and
      chemical mutagens. 

PMID- 24310287
TI  - Studies on intravitally-determined interrelationships between the activity of
      asparagine and alanine aminotransferases in blood serum and the fattering growth
      and meat yield of pigs.
AB  - As part of studies on early intravital indices of fattening growth and meat
      yield, an attempt was made to determine the interrelationship between the
      activity level of asparagine and alanine aminotransferases during early growth (4
      months) and meat yield, (determined on six months) old animals, and the fattening
      growth of pigs.The material for this investigation was comprised of 91 pigs of
      the Polish Landrace breed and 66 pigs of the Large-White Polish breed from the
      state breeding farm at Lubiana. The conclusions of the research are as follows:
      1. A significant positive correlation was found between the activity of AspAT and
      average 'live' growth rate (r=0.276), and a highly significant positive
      correlation was found between the activity of this enzyme and a performance
      testing selection index (r=0.354) in the case of the Large-White Polish breed. 2.
      A highly positive correlation coefficient between the activity of alanine
      aminotransferases and the mean 'live' rate of growth (r=0.347) was found in the
      Polish Landrace breed. 3. It is suggested that the AspAT level in the Large-White
      Polish breed and the ALAT level in the Polish Landrace breed may be used as a
      criterion of selection at early stages of growth (4 months) to predict meat and
      fattening output. 

PMID- 24310288
TI  - Responses upon multiple administration of L-thyroxine in hens.
AB  - Studies on the influence of repeated injections of L-thyroxine on enzyme activity
      and total protein level in the blood plasma of White Rock and Sussex hens have
      shown that: 1. The total protein level in both races decreased significantly. 2.
      Activity of aldolase increased in White Rock hens while in Sussex hens it
      increased considerably only after the last injection. 3. Activity of alanine
      aminotransferase did not change in White Rock hens and increased in the blood
      plasma of Sussex hens. 4. In both races, the activity of aspartate
      aminotransferase increased initially and changed after L-thyroxine injection. 5.
      Activity of alkaline phosphatase increased in White Rock hens, while in Sussex
      hens it decreased. 6. Statistically significant differences between activities of
      examined enzymes in both races after L-thyroxine administration were found. 

PMID- 24310289
TI  - Direct infection of embryogenic tissue cultures of haploidBrassica napus with
      resting spores ofPlasmodiophora brassicae.
AB  - A direct infection of cultured tissue with resting spores of the obligate
      endoparasitePlasmodiophora brassicae has been made possible by using stem embryo
      cultures of haploid rape. The fungus develops and completes its lifecycle in the
      cultured cells. The results are discussed in connection with the possibility of
      using this system to select for resistance to the pathogen. 

PMID- 24310290
TI  - Two locus models of selection and mutation within and among full-sib lines.
AB  - General models for continued full-sib mating with two diallelic autosomal loci
      taking account of linkage, mutation and selection within and among lines are
      considered. The problems are first approached by deriving the full probability
      transition matrix, taking account of linkage, mutation and within-line selection.
      Exact solutions to the equilibrium system are possible, but the computational
      effort is prohibitive, and this is exacerbated by the introduction of between
      line selection. A second approach is based on decomposing the transition matrix
      into blocks whose properties suggest approximations that lead to a rapid
      iterative solution of the equilibrium system. Extensive numerical analysis of
      models of within-line selection and of combined within- and between-line
      selection were made. The results show that equilibrium values are essentially
      independent of the degree of linkage under models of within-line selection. This
      is because mutation plays a dominant role in determining equilibrium structure.
      Results from models of combined within- and between-line selection show that
      between-line selection has the dominant influence on gene frequency equilibrium.
      Both within-line and between-line selection produce appreciable linkage
      disequilibrium only when selection is disruptive. The results also suggest that
      much of the twolocus equilibrium structure can be predicted from a knowledge of
      single-locus equilibria. 

PMID- 24310291
TI  - Cycloheximide resistance in carrot culture.

PMID- 24310292
TI  - What is the optimal management of chronic rhinosinusitis in cystic fibrosis?
AB  - PURPOSE OF REVIEW: Over the past four decades, the average life expectancy for
      patients with cystic fibrosis (CF) has increased from 13 to 37 years of age. With
      increasing survival and improved pulmonary management, otolaryngologists are now
      seeing an increasing number of CF patients with chronic rhinosinusitis (CRS).
      Although CRS is a commonly treated disease process, there are a number of
      subtleties specific to CF. As the life expectancy of CF patients increases,
      quality of life issues gain importance. It is essential for otolaryngologists to
      understand the current therapeutic modalities to treat this challenging subset of
      CRS patients. RECENT FINDINGS: The sinonasal mucosa of CF patients has distinct
      differences including impaired mucociliary clearance and a predominantly
      neutrophilic polyp profile. Performing more aggressive surgical intervention,
      especially in the setting of revision cases may lead to improved outcomes. A
      recent study demonstrated that extensive sinus surgery with postoperative
      management can eradicate pathogenic bacteria from the sinuses of CF patients for
      up to 1 year. SUMMARY: With increasing life expectancy in CF, patients will
      require long-term follow-up with an otolaryngologist. Understanding the
      intricacies of the presentation of this disease in patients with CF is important
      for optimizing management.

PMID- 24310293
TI  - T-cell receptor signaling induces proximal Runx1 transactivation via a
      calcineurin-NFAT pathway.
AB  - Runx1 transcription factor is a key player in the development and function of T
      cells. Runx1 transcripts consist of two closely related isoforms (proximal and
      distal Runx1) whose expressions are regulated by different promoters. Which Runx1
      isoform is expressed appears to be tightly regulated. The regulatory mechanism
      for differential transcription is, however, not fully understood. In this study,
      we investigated the regulation of the proximal Runx1 promoter in T cells. We
      showed that proximal Runx1 was expressed at a low level in naive T cells from
      C57BL/6 mice, but its expression was remarkably induced upon T-cell activation.
      In the promoter of proximal Runx1, a highly conserved region was identified which
      spans from -412 to the transcription start site and harbors a NFAT binding site.
      In a luciferase reporter assay, this region was found to be responsive to T-cell
      activation through Lck and calcineurin pathways. Mutagenesis studies and
      chromatin immunoprecipitation assay indicated that the NFAT site was essential
      for NFAT binding and transactivation of the proximal Runx1 promoter. Furthermore,
      TCR signaling-induced expression of proximal Runx1 was blocked by treatment of
      cells with cyclosporin A. Together, these results demonstrate that the
      calcineurin-NFAT pathway regulates proximal Runx1 transcription upon TCR
      stimulation. 

PMID- 24310294
TI  - Safety and efficacy of ascending aorta cannulation during repair of acute type A
      aortic dissection (PA29-04): "Presented at the 65th Annual Scientific Meeting of
      the Japanese Association for Thoracic Surgery".
AB  - OBJECTIVE: Antegrade central perfusion for acute Stanford type A aortic
      dissection prevents malperfusion and retrograde cerebral embolism during
      cardiopulmonary bypass. Prompt establishment of antegrade perfusion via the
      ascending aorta may improve surgical results of type A dissections, especially in
      situations of hemodynamic instability. Thus, we evaluated the safety and efficacy
      of cannulation of the dissected ascending aorta in acute type A dissection.
      METHODS: We reviewed the medical charts of patients undergoing repair of acute
      ascending aortic dissection (n = 52) from April 2010 to April 2013. Cannulation
      was accomplished in 29 patients via the ascending aorta (central) and in 23
      patients via the femoral or axillary artery (peripheral). The ascending aorta was
      routinely cannulated using Seldinger technique under epiaortic ultrasound
      guidance. Comorbidities, mortality, complications, and durations of hospital
      stays were compared for the groups. RESULTS: In all cases, routine cannulation of
      the ascending aorta was safely performed with no resultant malperfusion or
      thromboembolism. Mean operative duration, cardiopulmonary bypass time, intubation
      time, and intensive care unit stay were significantly shorter in the central
      group. Two patients (6.8 %) in the central group died compared with four patients
      (17.3 %) in the peripheral group (P = 0.005). CONCLUSIONS: Antegrade central
      perfusion via the ascending aorta, a simple and safe technique that enables rapid
      establishment of antegrade systemic perfusion, was as safe as peripheral
      cannulation in patients with type A acute aortic dissection.

PMID- 24310295
TI  - Secondary endoscopic submucosal dissection for residual or recurrent tumors after
      gastric endoscopic submucosal dissection.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is a widely accepted technique
      for the management of gastric tumors. However, residual or recurrent tumors can
      occur after ESD; currently, there is no adequate management strategy for these
      tumors. Thus, the aim of the present study was to establish a strategy of
      secondary ESD (sESD) for cases with positive lateral margins (LM+), which cause
      post-ESD residual or recurrent tumors. METHODS: Fifty-three lesions that were
      subjected to ESD were diagnosed as LM+ with suspected local residual tumor. The
      short- and long-term outcomes of early sESD (performed shortly after the initial
      ESD in LM+ cases to prevent local recurrence) were retrospectively compared with
      those of late sESD (performed after the detection of recurrent tumors). RESULTS:
      Of the 53 LM+ cases, the local residual positive rate was 38.5 % (10/26) in those
      undergoing early sESD or additional surgery and the local recurrence rate was
      29.6 % (8/27) in those that were not treated. Thus, the overall incidence of
      residual or recurrent tumors in LM+ cases was 34.0 % (18/53). Both early and late
      sESD had favorable outcomes with no severe complications: 100 % of early sESD
      resections were curative, compared with 86.7 % of late sESD resections, over the
      course of a mean (+/-SD) observation period of 50.8 +/- 16.7 months. The
      performance of early sESD was significantly greater than that of late sESD (in
      terms of dissection speed). CONCLUSIONS: Early sESD is more reliable than late
      sESD as a therapeutic strategy for salvaging residual tumors and for preventing
      recurrence. However, if a tumor has already recurred, late sESD remains useful.

PMID- 24310296
TI  - Nailfold capillary abnormalities in erectile dysfunction of systemic sclerosis: a
      EUSTAR group analysis.
AB  - OBJECTIVE: The objective of this study was to analyse an association between
      nailfold capillary abnormalities and the presence and severity of erectile
      dysfunction (ED) in men with SSc. METHODS: A cross-sectional analysis of the
      prospective European League Against Rheumatism (EULAR) Scleroderma Trial and
      Research database was performed. Men with SSc were included if they had undergone
      nailfold capillaroscopy and simultaneous ED assessment with the 5-item
      International Index for Erectile Function (IIEF-5). RESULTS: Eighty-six men met
      the inclusion criteria. Eight men (9.3%) had not had sexual intercourse and could
      not be assigned an IIEF-5 score. Sixty-nine of the 78 men (88.5%) with an IIEF-5
      score had nailfold capillary abnormalities, of whom 54 (78.3%) suffered from ED.
      Nine men (11.5%) had no nailfold capillary abnormalities, of whom six (66.7%) had
      ED (P = 0.44). ED was more frequent in older men (P = 0.002) and in men with
      diffuse disease (P = 0.06). Men with abnormal capillaroscopy had a higher median
      EULAR disease activity than men without (P = 0.02), a lower diffusing capacity of
      the lung (P = 0.001) and a higher modified Rodnan skin score (P = 0.04), but mean
      IIEF-5 scores did not differ [15.7 (S.D. 6.2) vs 15.7 (S.D. 6.3)]. IIEF-5 scores
      did not differ between men with early (n = 12), active (n = 27) or late (n = 27)
      patterns (IIEF-5 scores of 17.9, 16.3 and 14.7, respectively). There were no
      differences in the prevalence of early, active and late capillaroscopy patterns
      between men with or without ED. CONCLUSION: Neither the presence or absence of
      abnormal capillaroscopy findings nor the subdivision into early, active and late
      patterns is associated with coexistent ED in SSc.

PMID- 24310297
TI  - Predictors of access to care in juvenile systemic lupus erythematosus: evidence
      from the UK JSLE Cohort Study.
AB  - OBJECTIVE: The objective of this study was to investigate factors that may
      influence the interval between symptom onset and JSLE diagnosis. METHODS: Data
      from all patients recruited to the UK JSLE Cohort Study between 2006 and 2011 and
      meeting ACR criteria for lupus were analysed. Variables associated with time
      between symptom onset and diagnosis were identified using correlation tests.
      Linear regression was used to identify independent predictors of access to care.
      RESULTS: Two hundred and fifty-seven children with JSLE were included in the
      analysis (216 females, 41 males, ratio 5.3:1). The median time from symptom onset
      to diagnosis was 0.4 years (range 0.0-14.1 years, interquartile range 0.2-1.4). A
      linear regression model identified being of African or Caribbean origin (P =
      0.006), Asian (P = 0.045), referred by a paediatrician (P = 0.047) or having
      nephritis (P = 0.045) at presentation as independent predictors of shorter time
      to diagnosis. Being of Caribbean or Asian origin, compared with white, was
      associated with a 56% and 37% reduction in geometric mean time to diagnosis,
      respectively. Similarly, being referred to paediatric rheumatology by a
      paediatrician or having nephritis at presentation was also associated with a 32%
      and 36% reduction in geometric mean time to diagnosis, respectively. CONCLUSION:
      Within this national UK cohort, ethnic origin, initial source of referral and
      having lupus nephritis at presentation were strong predictors of the interval to
      establishing a diagnosis of JSLE.

PMID- 24310298
TI  - Pulmonary function and autoantibodies in a long-term follow-up of juvenile
      dermatomyositis patients.
AB  - OBJECTIVES: Pulmonary disease is a rare complication in JDM, described in only a
      few studies. This long-term follow-up study aimed to (i) describe pulmonary
      involvement in a national cohort of JDM patients estimated by conventional
      spirometry, (ii) compare pulmonary impairment with overall JDM outcome, and (iii)
      identify possible associations between pulmonary impairment and myositis-specific
      autoantibodies (MSAs). METHODS: Fifty-one JDM patients performed conventional
      spirometry in a cross-sectional follow-up study. The scores of the Myositis
      Damage Index (MDI), Myositis Damage by visual analogue scale (MYODAM-VAS) and
      physician's global damage assessment were used to estimate JDM outcome. ANAs,
      MSAs and myositis-associated autoantibodies were analysed in all patients.
      RESULTS: Forty-two patients (82%) (mean follow-up time 14.3 years) had normal
      lung function. Four patients (8%) were diagnosed with JDM-related restrictive
      interstitial lung disease. No patients reported pulmonary symptoms. Patients with
      restrictive pulmonary function had increased long-term damage estimated by MDI (P
      = 0.008), MYODAM-VAS (P = 0.04), global assessment (P = 0.03) and number of organ
      systems involved (P = 0.009). We found significant correlation between the
      restrictive pulmonary function test and damage by the MDI (r = 0.43, P = 0.003),
      MYODAM-VAS (r = 0.44, P = 0.002), and global damage assessment (r = 0.43, P =
      0.003). No association was found between the restrictive pulmonary function test
      and autoantibodies. CONCLUSION: In a long-term follow-up study of JDM patients,
      the majority of patients demonstrated normal lung function. However, restrictive
      pulmonary impairment was identified in 8% of patients, indicating a need for
      repetitive pulmonary follow-up in JDM patients. Restrictive pulmonary involvement
      was associated with increased long-term JDM damage.

PMID- 24310299
TI  - Genomics of BK viremia in kidney transplant recipients.
AB  - BACKGROUND: This study aimed to investigate global gene expression profiles of BK
      viremia and nephropathy (BKVN) samples using microarrays to investigate the
      immunologic response to BK virus. METHODS: Patients were monitored for BK viremia
      in the blood monthly for 6 months, then at 9 and 12 months after kidney
      transplantation. BKVN and normal transplant kidney biopsy samples, and whole
      blood samples of patients with and without BK viremia were analyzed by Affymetrix
      Human Gene 1.0 ST Arrays. RESULTS: During a mean follow-up of 917+/-325 days, 61
      of the 289 patients (21%) developed BK viremia at a median 149 (27, 1,113) days
      after transplantation with a median peak PCR titers of 35,900 (1,000, 2,677,000).
      The only significant risk factor for development of BK viremia was induction with
      anti-thymocyte globulin (P=0.03). Only four patients developed BKVN (1.3%).
      Pathogenesis-based transcript analysis revealed a significant increased
      expression of interferon-gamma and rejection induced (GRIT), quantitative
      cytotoxic T-cell (QCAT), quantitative constitutive and alternate macrophage, B
      cell and natural killer cell-associated transcripts (NKAT), indicating an active
      inflammatory immune response in BKVN biopsies (n=3) compared to normal transplant
      kidney biopsies with (n=3) and without BK viremia (n=11). The whole blood gene
      expression profiles of 19 BK viremia patients revealed significant increased
      expression of GRIT, QCAT, and NKAT compared to 14 patients without viremia.
      CONCLUSIONS: The results showed increased activity of cytotoxic T cells and
      natural killer cells in BKVN and viremia samples resembling acute rejection and
      suggested the involvement of both adaptive and innate immunity.

PMID- 24310300
TI  - Design and efficient synthesis of a pillar[5]arene-based [1]rotaxane.
AB  - A pillar[5]arene-based [1]rotaxane was simply prepared in a high yield of 73%.
      Its stucture was confirmed by (1)H NMR, 2D NMR spectra, mass spectra and
      theoretical calculation. 

PMID- 24310301
TI  - Effects of pigment-deficient mutants on the accumulation of photosynthetic
      proteins in maize.
AB  - We have monitored the accumulation of photosynthetic proteins in developing
      pigment-deficient mutants of Zea mays. The proteins examined are the CO2-fixing
      enzymes, phoshoenolpyruvate carboxylase (E.C. 4.1.1.31) and ribulose-1,5
      bisphosphate carboxylase (E.C.4.1.1.39), and three thylakoid membrane proteins,
      the light-harvesting chlorophyll a/b binding protein (LHCP) of photosystem II,
      the 65 kilodalton chlorophyll a binding protein of photosystem I and the alpha
      subunit polypeptide of coupling factor I. Using a sensitive protein-blot
      technique, we have compared the relative quantities of each protein in mutants
      and their normal siblings. Carboxylase accumulation was found to be independent
      of chlorophyll content, while the amounts of the thylakoid proteins increase at
      about the same time as chlorophyll in delayed-greening mutants. The relative
      quantity of LHCP is closely correlated with the relative quantity of chlorophyll
      at all stages of development in all mutants. Because pigment-deficient mutants
      are arrested at early stages in chloroplast development, these findings suggest
      that the processes of chloroplast development, chlorophyll synthesis and
      thylakoid protein accumulation are coordinated during leaf development but that
      carboxylase accumulation is controlled by different regulatory mechanisms. A
      white leaf mutant was found to contain low levels of LHCP mRNA, demonstrating
      that the accumulation of LHCP mRNA is not controlled exclusively by phytochrome. 

PMID- 24310302
TI  - Use of synthetic oligodeoxyribonucleotides and primed cDNA as probes for pea
      (Pisum sativum L.) RNA and genomic DNA sequences.
AB  - Two oligonucleotide sequences were synthesised by a solid-phase phosphotriester
      method. One of these sequences, A was a copy of part of a characterised cDNA
      clone encoding the basic subunit of legumin, a seed storage protein of Pisum
      sativum L. (garden pea); the other sequence B was predicted to be complementary
      to the 5' region of legumin mRNA on the basis of the amino acid sequence of
      legumin acidic subunits and most likely codon usage. Sequence A was shown to
      hybridise specifically to a legumin cDNA clone and to legumin mRNA. Sequence B
      did not hybridise specifically to legumin mRNA and was concluded not to be
      correctly complementary to legumin mRNA. Sequence A was used as a primer for cDNA
      synthesis using pea seed mRNA as a template. The cDNA so produced hybridised
      specifically to a legumin cDNA clone, to legumin mRNA, and to sequences encoding
      legumin in a restriction digest of pea genomic DNA. It is suggested that such
      oligonucleotide primed cDNAs may be of general value in probing eukaryotic
      genomic DNA. 

PMID- 24310303
TI  - Site of synthesis of spinach chloroplast ribosomal proteins and formation of
      incomplete ribosomal particles in isolated chloroplasts.
AB  - Chloroplast ribosomal proteins from spinach have been prepared in the presence of
      a protease inhibitor and some modifications have been introduced to the previous
      characterization of the 50S subunits (Mache et al., MGG, 177, 333, 1980): 33
      ribosomal proteins are detected instead of 34. No change has been observed for
      the 30S subunits.Using a light-driven system of protein synthesis it is shown
      that up to ten ribosomal proteins of the 30S and eight proteins of the 50S
      subunits are made in the chloroplast.Newly synthesized ribosomal subunits have
      been analysed on CsCl gradients after sedimentation at equilibrium, allowing the
      separation of fully assembled subunits from incomplete ribosomal particles. Most
      of the newly made 50S subunits are fully assembled (rho=1.634). A small amount of
      incomplete 50S particles (rho=1.686) is detectable. Newly made 30S subunits
      (rho=1.598) and incomplete 30S particles (rho=1.691) are also observed. The
      ribosomal proteins of the incomplete 30S have been determined. They contain eight
      or nine of the 30S-proteins, seven of which are synthesized within the
      chloroplast. It is suggested that incomplete ribosomal particles resulted from a
      step in the assembly of ribosomal subunits. 

PMID- 24310304
TI  - Two cDNA clones coding for the legumin protein of Pisum sativum L. contain
      sequence repeats.
AB  - The sequence of two cDNA clones coding for the whole of the beta-subunit and most
      of the alpha-subunit of legumin are presented together with a considerable amount
      of protein sequence data to confirm the predicted amino acid sequence. A unique
      feature shown by these cDNAs is the presence of three 56 base pair tandem repeats
      in the region encoding the C terminal of the alpha polypeptide. The tandem
      repeats are also exhibited in the predicted polypeptide sequence as three 18
      amino acid repeats which contain extremely high proportions of polar, mainly
      acidic, residues. The new sequences are compared to the previously published
      sequence of some shorter legumin cDNAs (Nature 295: 76-79). In the region where
      the sequences overlap, the previous cDNAs differ from the new ones by only a few
      base substitutions but most of the repeated region is not present though the
      sequences on either side are. The possibility that the absence of the repeats may
      reflect the difference between two types of legumin gene, rather than an artefact
      of the cloning of the cDNAs, is discussed. 

PMID- 24310305
TI  - Accurate processing and pseudouridylation of chloroplast transfer RNA in a
      chloroplast transcription system.
AB  - The trancription of a cloned trnV1-trnN1-trnR1 cluster from Euglena gracilis
      chloroplast (ct) DNA and the processing of a tRNA(Val)-tRNA(Asn)-tRNA(Arg)
      polycistronic precursor were studied in a spinach ct transcription extract. A
      soluble ct RNA polymerase selectively transcribes the trnV1-trnN1-trnR1-trnL1
      locus in the EcoG fragment from the Euglena ct genome. Restriction enzyme
      modified templates and RNA fingerprint analysis were used to confirm that the
      tRNA genes were correctly transcribed. The tRNA(Val)-tRNA(Asn)-tRNA(Arg)
      polycistronic precursor transcribed by RNA polymerase III in a HeLa cell extract
      was used as a substrate to demonstrate that a ct tRNA precursor molecule is
      correctly processed by the ct tRNA processing enzymes. The oligonucleotide
      pattern of tRNAs processed in vitro from the tRNA(Val)-tRNA(Asn)-RNA(Arg)
      polycistronic precursor is indistinguishable from tRNA(Val), tRNA(Asn) and
      tRNA(Arg) transcribed by the ct RNA polymerase and processed in the ct
      transcription extract. The 3'-CCAOH is added to the tRNAs by a 3'
      nucleotidyltransferase after correct processing of the 3' terminus. Correct
      pseudouridylation was demonstrated for uridine residues in a tRNA(Met) m molecule
      transcribed from a spinach ct trnM1 locus. Thus, the enzymatic activities
      involved in tRNA biosynthesis in vitro include DNA-dependent (tDNA) RNA
      polymerase, a 5'-processing activity (RNase P-like), a 3'-exonuclease, an
      endoribonuclease involved in 3'-tRNA maturation, a tRNA nucleotidyltransferase,
      and pseudouridylate synthetase. 

PMID- 24310306
TI  - Structure of soybean Kunitz trypsin inhibitor mRNA determined from cDNA by using
      oligodeoxynucleotide primers.
AB  - Oligodeoxynucleotides complementary to the deduced mRNA sequence of soybean
      Kunitz trypsin inhibitor (KTI) were used to prime the synthesis of cDNA from
      soybean cotyledon total poly(A) RNA. The primed cDNA was used to select clones
      from a Glycine max cotyledon cDNA library. Two out of twelve hybridizing clones
      were shown to contain KTI cDNA. The nucleotide sequence of one clone, pSTI 9-2,
      was determined and it was found to encompass the complete protein coding region
      of KTI excet for three C-terminal residues. Trypsin inhibitor is synthesized with
      a 25 amino acid hydrophobic N-terminal sequence presumed to be a signal peptide.
      The mature polypeptide encoded by pSTI 9-2 agrees with the published amino acid
      composition of KTI, but contains two discrepancies at the peptide sequence level.

PMID- 24310307
TI  - Erratum.

PMID- 24310308
TI  - ACMG technical standards and guidelines for genetic testing for inherited
      colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH
      associated polyposis).
AB  - Lynch syndrome, familial adenomatous polyposis, and Mut Y homolog (MYH)
      associated polyposis are three major known types of inherited colorectal cancer,
      which accounts for up to 5% of all colon cancer cases. Lynch syndrome is most
      frequently caused by mutations in the mismatch repair genes MLH1, MSH2, MSH6, and
      PMS2 and is inherited in an autosomal dominant manner. Familial adenomatous
      polyposis is manifested as colonic polyposis caused by mutations in the APC gene
      and is also inherited in an autosomal dominant manner. Finally, MYH-associated
      polyposis is caused by mutations in the MUTYH gene and is inherited in an
      autosomal recessive manner but may or may not be associated with polyps. There
      are variants of both familial adenomatous polyposis (Gardner syndrome--with
      extracolonic features--and Turcot syndrome, which features medulloblastoma) and
      Lynch syndrome (Muir-Torre syndrome features sebaceous skin carcinomas, and
      Turcot syndrome features glioblastomas). Although a clinical diagnosis of
      familial adenomatous polyposis can be made using colonoscopy, genetic testing is
      needed to inform at-risk relatives. Because of the overlapping phenotypes between
      attenuated familial adenomatous polyposis, MYH-associated polyposis, and Lynch
      syndrome, genetic testing is needed to distinguish among these conditions. This
      distinction is important, especially for women with Lynch syndrome, who are at
      increased risk for gynecological cancers. Clinical testing for these genes has
      progressed rapidly in the past few years with advances in technologies and the
      lower cost of reagents, especially for sequencing. To assist clinical
      laboratories in developing and validating testing for this group of inherited
      colorectal cancers, the American College of Medical Genetics and Genomics has
      developed the following technical standards and guidelines. An algorithm for
      testing is also proposed.

PMID- 24310309
TI  - Developing a public health-tracking system for follow-up of newborn screening
      metabolic conditions: a four-state pilot project structure and initial findings.
AB  - PURPOSE: The aim of this study was to describe the methods, cases, and initial
      results of a pilot project using existing public health data collection programs
      (birth defect surveillance or newborn screening) to conduct long-term follow-up
      of children with metabolic disorders. METHODS: California, Iowa, New York, and
      Utah expanded birth defect surveillance or newborn screening programs to collect
      long-term follow-up data on 19 metabolic disorders. Data elements to monitor
      health status and services delivered were identified, and record abstraction and
      data linkages were conducted. Children were followed up through to the age of 3
      years. RESULTS: A total of 261 metabolic cases were diagnosed in 1,343,696 live
      births (19.4 cases/100,000; 95% confidence interval = 17.1-21.8). Four deaths
      were identified. Children with fatty acid oxidation disorders had a higher
      percentage of health service encounters compared with children with other
      disorders of at least one health service encounter (hospitalization, emergency
      room, metabolic clinic, genetic service provider, or social worker) except for
      hospitalizations; children with organic acid disorders had a higher percentage of
      at least one hospitalization during their third year of life than children with
      other disorders. CONCLUSION: Existing public health data programs can be
      leveraged to conduct population-based newborn screening long-term follow-up. This
      approach is flexible according to state needs and resources. These data will
      enable the states in assessing health burden, assuring access to services, and
      supporting policy development.

PMID- 24310310
TI  - Preferences for results delivery from exome sequencing/genome sequencing.
AB  - PURPOSE: The aim of this study was to explore the implications of sequencing
      information and stated preferences for return of results among research
      participants. METHODS: Six focus groups were held with 39 ClinSeq participants.
      The groups included participants who had received results, those who had not,
      those affected with cardiovascular disease, and healthy adults. Audio recordings
      of the sessions were transcribed and coded and analyzed for themes. RESULTS: All
      participants expressed interest in receiving results that are medically
      actionable, nonactionable, carrier, and less so variants that cannot be
      interpreted. Most participants preferred to receive results in person, although
      several endorsed use of Internet-based resources that they could return to.
      Participants identified benefits for health management along with satisfying
      curiosity, making scientific contributions, and partnering in research. Value was
      seen in gaining control over health risks. Concerns were distress and/or fear
      that may result. Some participants were opposed to or ambivalent about learning
      certain types of results, particularly those having to do with diseases that were
      incurable or that might have implications for the health of their children.
      CONCLUSION: There was relative enthusiasm about the value of learning sequencing
      information, yet it was tempered by concern about negative feeling responses and
      aversion to learning about incurable conditions.

PMID- 24310311
TI  - Electrical/optical dual-function redox potential transistor.
AB  - We demonstrate a new type of transistors, the electrical/optical "dual-function
      redox-potential transistors", which is solution processable and environmentally
      stable. This device consists of vertically staked electrodes that act as gate,
      emitter and collector. It can perform as a normal transistor, whilst one
      electrode which is sensitised by dye enables to generate photocurrent when
      illuminated. Solution processable oxide-nanoparticles were used to form various
      functional layers, which allow an electrolyte to penetrate through and,
      consequently, the current between emitter and collector can be controlled by the
      gate potential modulated distribution of ions. The result here shows that the
      device performs with high ON-current under low driving voltage (<1 V), while the
      transistor performance can readily be controlled by photo-illumination. Such
      device with combined optical and electrical functionalities allows single device
      to perform the tasks that are usually done by a circuit/system with multiple
      optical and electrical components, and it is promising for various applications. 

PMID- 24310312
TI  - The outcome of bifocal surgical resection in non-small cell lung cancer with
      synchronous brain metastases: results of a single center retrospective study.
AB  - BACKGROUND: The reported median survival in patients with non-small cell lung
      cancer (NSCLC) metastases to the brain varies from 3 to 12 months with combined
      treatment modalities. Bifocal surgical resection of synchronous brain metastasis
      and primary NSCLC has not been reported widely, and there have been only a small
      number of articles published in the literature. The aim of this retrospective
      study was to evaluate the prognostic factors among patients undergoing bifocal
      surgical resection. MATERIALS AND METHODS: We retrospectively analyzed 28
      patients who had a solitary metastatic brain lesion at the time of diagnosis, and
      underwent synchronous surgical resection of the brain metastasis and primary lung
      tumor. Survival time was measured in all the patients from the date of craniotomy
      until death or the most recent date of follow-up for those still surviving.
      RESULTS: Mean age was 53 years. The mean length of follow-up was 23.6 (4-69)
      months. The overall survival rates were 79, 42, and 8% at the 1st, 2nd, and 5th
      years, respectively. The median length of survival was 24 +/- 3.8 months. The
      median survival was found to be statistically significantly lower for the stage
      T3 tumors when compared with both stage T1 and T2 tumors (p = 0.037). CONCLUSION:
      NSCLC patients with resectable solitary cranial metastasis, low locoregional
      stage (stages IA, IB, IIA) in which T3 status is counted out, with no mediastinal
      lymph node involvement or any other extrathoracic spread will mostly benefit from
      consecutive complete resection of both tumors and are supposed to have a better
      survival.

PMID- 24310313
TI  - The workplace as a context for the socialization of youth.
AB  - A number of respected social critics, including the President's Science Advisory
      Committee (PSAC), have recommended the earlier integration of adolescents into
      the workplace. The PSAC Panel on Youth (1973) claims that work settings provide
      opportunities for developing and exercising personal responsibility, taking
      responsibility for the welfare of others, and establishing more extensive
      instrumental and social relations with nonfamilial adults. This study of
      "naturally occurring" employment among high school students examines these claims
      about the nature of the workplace. Drawing on interview, questionnaire, and
      observational data, we argue that the PSAC's expectations are somewhat
      optimistic. With respect to personal responsibility taking, although many
      adolescent workers have opportunities for self-management and report performing
      assigned tasks dependably, very few report going "beyond the call of duty." With
      respect to social responsibility, workers experience only modest levels of task
      interdependence and centrality to a team effort; yet substantial numbers of
      adolescent workers feel that their work serves a socially useful purpose.
      Finally, with respect to intergenerational contact, the workplace fails to induce
      meaningful interaction with adults. Taken together, the results of this study
      suggest that if the workplace is to become a truly vital context for adolescent
      socialization, it needs to be designed more deliberately with such aims in mind. 

PMID- 24310314
TI  - Selective attention and self-control in delinquent adolescents.
AB  - Research studies are briefly reviewed to examine the hypothesis that delinquent
      adolescents may process information in a different manner than non-delinquents.
      Studies suggest that delinquents may have less control over which information
      they attend to, may expose themselves to more stimulation, may process
      information more slowly, and may selectively attend to different information than
      matched controls. Findings from a recent study are presented in support of the
      latter hypothesis. A clinical example illustrates how these attention differences
      may appear in the course of treatment. 

PMID- 24310315
TI  - Staff cohesion in residential treatment.
AB  - There is a continuous recognition in the literature of residential treatment of
      the need for studies to assess the impact of key variables which constitute a
      residential milieu on the treatment environment and, by implication, on the
      treatment outcome. One key variable is staff cohesion. The present study explored
      the effect of varying levels of staff cohesion on the treatment environment in a
      residential treatment center for disturbed adolescents. The results suggest that
      the variables Support, Personal Problem Orientation, Autonomy, Practical
      Orientation, and Staff Control are significantly affected by varying levels of
      staff cohesion. However, the clients' perception of their environment did not
      appear to be influenced by staff cohesion level. 

PMID- 24310316
TI  - Self-recognition of the body and its parts during late adolescence.
AB  - Male and female student volunteers were photographed nude in three orientations:
      front, side, and rear. One month later, they were asked to identify their bodies
      or bodily parts from an array of seven photographs grouped according to height
      and linearity. Thirty judgments of the full body, multiple parts, and single
      parts were made, including the head, thorax, abdomen, arms and legs, as well as
      the torso and top and bottom halves of the body. Females took significantly
      longer to identify themselves than did males and frontal identifications were
      carried out quicker than rear identifications, which in turn were judged quicker
      than side orientations. The breasts were found to be the most important secondary
      sexual characteristic for females, and bodily hair for males. The genitals were
      judged quickly and accurately by males. The results are discussed in terms of ego
      involvement, narcissism, and the increased attention given to the body during
      adolescence. 

PMID- 24310317
TI  - Assessment of quality of life in children and youth with autism spectrum
      disorder: a critical review.
AB  - PURPOSE: To review the use of quality of life (QOL) measures utilised in children
      and youth with autism spectrum disorder (ASD). METHODS: Relevant articles were
      identified through database searches using MEDLINE, CINAHL Plus with Full Text
      and SPORTDiscus with Full Text via EBSCO Health Database, PsycINFO and ProQuest
      Health and Medicine (from 2000 to May 2013). Original research articles were
      included that measured QOL in children and youth with ASD aged 5-20 years.
      Searches were limited to articles from peer-reviewed journals, in English or
      German, and those available in full text. RESULTS: The search identified 1,165
      titles and 13 met the inclusion criteria. The review identified a number of QOL
      measures used in children and youth with ASD, with the most common one being the
      Pediatric Quality of Life InventoryTM (PedsQL). QOL measures using self-reports
      were uncommon, and the reliability and validity of QOL measures were not
      sufficiently reported for this population. Large discrepancies in QOL scores were
      found between self-reports and proxy-reports. Despite the differences in study
      design and methodological quality, there was consistency in the results among
      studies; children and youth with ASD provided lower QOL scores, particularly for
      social domains, compared to their healthy counterparts. CONCLUSIONS: The PedsQL
      is likely to be an appropriate QOL measure for use in children and youth with
      ASD. Future research should focus on examining the appropriateness, reliability
      and validity of QOL self-reports for use in this population.

PMID- 24310319
TI  - Mono lacunary phosphomolybdate supported on MCM-41: synthesis, characterization
      and solvent free aerobic oxidation of alkenes and alcohols.
AB  - A new catalyst comprising monolacunary phosphomolybdate and MCM-41 was
      synthesized and characterized by different physicochemical techniques. The
      catalytic activity was evaluated by carrying out solvent free aerobic oxidation
      of alkenes and alcohols. The catalyst showed 60% conversion of styrene and 28%
      conversion of benzyl alcohol. The superiority of the present catalytic system
      lies in obtaining better conversion under solvent free and aerobic conditions. 

PMID- 24310321
TI  - Capillaries as controlled release devices for insect pheromones and other
      volatile substances-A reevaluation : Part I. Kinetics and development of
      predictive model for glass capillaries.
AB  - Controlled release formulations are required for the dissemination of behavior
      modifying chemicals in insect control strategies. Among the types of formulations
      that have been used for some time are glass and plastic capillaries. Erratic
      release rates on field use of such capillaries prompted us to reexamine the
      release of volatile materials with regard to (1) kinetics of the release, (2) the
      effect of the vapor-air column above the liquid, and (3) developing a predictive
      model. Results indicate that the release is not zero order, and that the length
      of the vapor-air column is a critical factor of the system; a predictive model
      has been developed that will allow better design of capillary controlled-release
      formulations. 

PMID- 24310322
TI  - Capillaries as controlled release devices for insect pheromones and other
      volatile substances-A reevaluation : Part II. Predicting release rates from
      Celcon and Teflon capillaries.
AB  - A predictive model developed for the release rates of volatile materials from
      glass capillaries was invalid when tested with Celcon fibers used commercially in
      pheromone-based insect control strategies. Several factors which might explain
      the differences between the predicted and observed rates are discussed, and it is
      hypothesized that the topography of the fiber lumen is the major factor causing
      the observed rates to deviate from the predicted values and the large variation
      in rate from fiber to fiber. This hypothesis was tested using Teflon capillary
      fibers with both smooth and rough lumen walls and shown to be valid. This
      indicates that commercial hollow-fiber pheromone formulations can be improved
      both in efficiency and cost by careful selection of fiber material, improvement
      in fiber manufacturing, and the use of a predictive model in formulation design. 

PMID- 24310320
TI  - Convergent diversity-oriented side-chain macrocyclization scan for unprotected
      polypeptides.
AB  - Here we describe a general synthetic platform for side-chain macrocyclization of
      an unprotected peptide library based on the SNAr reaction between cysteine
      thiolates and a new generation of highly reactive perfluoroaromatic small
      molecule linkers. This strategy enabled us to simultaneously "scan" two cysteine
      residues positioned from i, i + 1 to i, i + 14 sites in a polypeptide, producing
      98 macrocyclic products from reactions of 14 peptides with 7 linkers. A
      complementary reverse strategy was developed; cysteine residues within the
      polypeptide were first modified with non-bridging perfluoroaryl moieties and then
      commercially available dithiol linkers were used for macrocyclization. The highly
      convergent, site-independent, and modular nature of these two strategies coupled
      with the unique chemoselectivity of a SNAr transformation allows for the rapid
      diversity-oriented synthesis of hybrid macrocyclic peptide libraries with varied
      chemical and structural complexities. 

PMID- 24310323
TI  - Isolation and partial characterization of phytotoxic compounds from lantana
      (Lantana camara L.).
AB  - Phytotoxic compounds obtained from methanol extracts of field-grown lantana
      (Lantana camara L.) were quantified in terms of their inhibition of ryegrass
      (Lolium multiflorum Lam.) seed germination and/or seedling growth. Subsequent
      partition of the aqueous fraction (derived from drying the MeOH extract in vacuo
      and redissolving in distilled water) at various pHs with solvents of differing
      polarity indicated the phytotoxic compounds were both polar and slightly acidic.
      Thin-layer Chromatographic separation of the acidic butanol fraction in a solvent
      mixture of butanol, acetic acid, water (4?1?5, by volume) yielded an active
      fraction with anR f value of 0.89-1.0 that was inhibitory to both root and shoot
      growth of ryegrass. Two other fractions withR f values of 0.04-0.23 and 0.41-0.57
      were inhibitory only to root but not shoot growth. 

PMID- 24310324
TI  - Sex pheromone of tobacco stem borer,Scrobipalpa heliopa (Lower) (Lepidoptera:
      Gelechiidae).
AB  - The major volatile component in the extract of the female sex pheromone gland
      ofScrobipalpa heliopa was shown to be (E)-3-tridecen-1-ol acetate (V). The
      identification was based on mass spectral analyses, comparison of retention times
      with those of synthetic compounds on polar, nonpolar, and liquid crystal gas
      chromatographic columns and microchemical studies. The latter included hydrolysis
      and reacetylation, and mass spectral studies of the derivatives formed by
      epoxidation and methoxymercuration-demercuration. Analysis of gland extracts by
      gas chromatography linked to electroantennography showed this component to be the
      only one with significant biological activity, similar to that of the synthetic
      compound. (E)-3-Tridecenyl acetate (V) attracted male moths to traps in the field
      while addition of theZ isomer (III) reduced the numbers of moths caught. 

PMID- 24310325
TI  - Pheromone receptor cell specificity in interpopulational hybrids ofIps pini
      (Coleoptera: Scolytidae).
AB  - Electrophysiological studies of pheromone receptor cells keyed to ispdienol were
      performed in laboratory-raised hybrids of the eastern and western populations of
      the pine engraver,Ips pini. As previously shown in the parental beetles, the
      receptor cells keyed to ipsdienol could be classified as two distinct types: one
      keyed to (+)- and one to (-)-ipsdienol. None of the 20 ipsdienol cells recorded
      from F1 hybrids were of an intermediate type. Recordings of the summated receptor
      responses (EAGs) showed no significant difference between parental beetles and
      hybrids. Similar results were obtained in reciprocal crosses, eastern females
      with western males and the reverse. Thus, there was no indication that sex-linked
      alleles determined the specificity of the ipsdienol receptor cell. The ratio
      between (+) and (-) cells was 14?6 in the hybrids compared to 1?12 in the western
      and 9?12 in the eastern populations. 

PMID- 24310318
TI  - Dapsone in dermatology and beyond.
AB  - Dapsone (4,4'-diaminodiphenylsulfone) is an aniline derivative belonging to the
      group of synthetic sulfones. In 1937 against the background of sulfonamide era
      the microbial activity of dapsone has been discovered. Shortly thereafter, the
      use of dapsone to treat non-pathogen-caused diseases revealed alternate
      antiinflammatory mechanisms that initially were elucidated by inflammatory animal
      models. Thus, dapsone clearly has dual functions of both:
      antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to
      non-steroidal anti-inflammatory drugs. The latter capabilities primarily were
      used in treating chronic inflammatory disorders. Dapsone has been investigated
      predominantly by in vitro methods aiming to get more insights into the effect of
      dapsone to inflammatory effector cells, cytokines, and/or mediators, such as
      cellular toxic oxygen metabolism, myoloperoxidase-/halogenid system, adhesion
      molecules, chemotaxis, membrane-associated phospholipids, prostaglandins,
      leukotrienes, interleukin-8, tumor necrosis factor alpha, lymphocyte functions,
      and tumor growth. Moreover, attention has been paid to mechanisms by which
      dapsone mediates effects in more complex settings like impact of lifespan,
      stroke, glioblastoma, or as anticonvulsive agent. Additionally, there are some
      dermatological investigations in human being using dapsone and its metabolites
      (e.g., leukotriene B4-induced chemotaxis, ultraviolet-induced erythema). It could
      be established that dapsone metabolites by their own have anti-inflammatory
      properties. Pharmacology and mechanisms of action are determining factors for
      clinical use of dapsone chiefly in neutrophilic and/or eosinophilic dermatoses
      and in chronic disorders outside the field of dermatology. The steroid-sparing
      effect of dapsone is useful for numerous clinical entities. Future avenues of
      investigations will provide more information on this fascinating and essential
      agent.

PMID- 24310326
TI  - Chemoattraction between fry of Arctic char [Salvelinus alpinus (L.)] studied in a
      Y-maze fluviarium.
AB  - Attraction of fry of Arctic char [Salvelinus alpinus (L.)] to water conditioned
      by conspecifics of the same age was studied in a Y-maze fluviarium. Two types of
      experiments were run. In "up-swimming tests" (1), starting from the common leg of
      the Y-maze, a single fish was given the choice of entering one of the two
      upstream arms. In "gradient tests" (2), the momentary positions of a single char
      were time-lapse photographed in a test yard of this common shank. Strong
      attraction to conditioned water was observed in both types of tests. 

PMID- 24310327
TI  - Modes of defense in nematine sawfly larvae : Efficiency against ants and birds.
AB  - Ventral glands are common in nematine larvae (Hymenoptera: Symphyta), but they
      show various degrees of development and are functional for defense only in some
      species. In those species, volatile irritants are produced which are effective
      against ants. Alternative or complementary mechanisms against ants are the
      pubescence ofTrichiocampus spp., the foam pillars constructed byStauronema
      compressicornis, various movements of the abdomen, which occur independently of
      the glandular secretion in several species, immobility of the flat larvae
      ofNematinus luteus, and burrowing within plant tissues in gallicolous larvae or
      miners. Glandular development is not clearly related to the appearance of the
      larvae, either cryptic or aposematic. The secretion, even when it is produced in
      large amounts by species with well-developed glands, is only moderately efficient
      against great tits. Bright colors are found in gregarious larvae; these were
      accepted only with reluctance by great tits and sometimes rejected, even species
      in which the ventral glands are reduced. We suggest that the various volatile
      irritants secreted by ventral glands are aimed primarily against insects (e.g.,
      ants) and only secondarily against birds. 

PMID- 24310328
TI  - Anal gland secretions of the stoat (Mustela erminea) and the ferret (Mustela
      putorius formafuro) : Some additional thietane components.
AB  - Two new thietanes,cis- andtrans-2-ethyl-3-methylthietane, have been identified in
      the anal gland secretion of the stoat, and 2-isopropyl thietane has been
      characterized from the anal gland secretion of the ferret. Conflicting published
      data are reevaluated. 

PMID- 24310329
TI  - Feeding deterrency of some pyrrolizidine, indolizidine, and quinolizidine
      alkaloids towards pea aphid (Acyrthosiphon pisum) and evidence for phloem
      transport of indolizidine alkaloid swainsonine.
AB  - The feeding deterrency of a series of pyrrolizidine, indolizidine, and
      quinolizidine alkaloids and selected derivatives was measured against the pea
      aphid (Acyrthosiphon pisum Harris). The indolizidine alkaloid, castanospermine,
      was intensely active (ED50, 20 ppm) as were the quinolizidine alkaloids, but only
      modest feeding deterrency was observed with most of the pyrrolizidine alkaloids
      tested. The insect survival rate of aphids on a castanospermine-supplemented diet
      over 24 hr was also very low relative to the controls. Castanospermine does not
      inhibit aphid trehalase. The indolizidine alkaloid swainsonine occurred in the
      honeydew of pea aphid feeding on the locoweed,Astragalus lentiginosus. Since the
      pea aphid is a phloem feeder, swainsonine must be transported in the phloem. 

PMID- 24310330
TI  - Aggregation pheromones of the flat grain beetle,Cryptolestes pusillus
      (Coleoptera: Cucujidae).
AB  - Aggregation pheromones were isolated fromCryptolestes pusillus (Schonherr), a
      coleopteran pest of stored products. Porapak Q-captured beetle and frass
      volatiles were fractionated by preparative gas-liquid chromatography. The
      fractions were bioassayed with an arena olfactometer and/or with a two-choice,
      pitfall olfactometer. Three biologically active, male-produced compounds
      eliciting aggregation behavior from adultC. pusillus were isolated and identified
      by spectroscopic methods as (Z)-3-dodecenolide (I), (Z)-5-tetradecen-13-olide
      (II), and (Z,Z)-3,6-dodecadienolide (III). Compound I was the major volatile
      produced and was active alone. Compound II was not active alone, but synergized
      the response to I. Compound III was active alone at higher concentrations, but
      did not significantly increase the response when added to the most active mixture
      of I and II, and so it is probably not part of the aggregation pheromone.
      Pheromone production increased dramatically when the insects were aerated on a
      food source. 

PMID- 24310331
TI  - Aggregation pheromones of the grain beetle,cryptolestes turcicus (Coleoptera:
      Cucujidae).
AB  - Two biologically active macrolides were isolated from Porapak Q-captured beetle
      and frass volatiles ofCryptolestes turcicus (Grouvelle) and identified
      spectroscopically as (Z,Z)-5,8-tetradecadien-13-olide (I) and (Z)-5-tetradecen-13
      olide (II). Natural I was active alone and was synergized by inactive II. The
      pheromones were male-produced but attractive to both sexes. Pheromone production
      increased dramatically when insects were aerated on a food source. Pure (R)- and
      (S)-I were inactive, but mixtures of (R)- and (S)-I were active, the first
      reported instance of enantiomeric synergism in the Cucujidae. 

PMID- 24310332
TI  - Defensive secretion production in the tenebrionid beetle,Zophobas atratus :
      Effects of age, sex, and milking frequency.
AB  - Beetles were milked of their abdominal defensive secretion at three different
      frequencies over the first 36 days of adult life. Secretion production decreased
      greatly with age from a maximum of 94 nmol/day at 4-6 days to a basal level of
      about 25 nmol/day at 30-40 days. Ethyl- and methylquinone comprised the bulk of
      the secretion and were most strongly affected by age. Benzoquinone was most
      strongly affected by milking frequency. An average adult produced an estimated
      4445 nmol of total secretion in its 5-month life-span but had reservoirs large
      enough to store 11,000 nmol. Males produced more secretion than females because
      of their larger size and inherent sexual differences. As they aged, mated females
      showed a more rapid decrease in production that virgin females. The defensive
      system appears to be programed to charge glands rapidly with secretion early in
      adult life and fall of to a low recharge rate little affected by discharge. 

PMID- 24310333
TI  - Constituents of osmeterial secretion of pre-final instar larvae of citrus
      swallowtail,Papilio demodocus (Esper) (Lepidoptera: Papilionidae).
AB  - The defensive osmeterial secretion of pre-final instar larvae of the citrus
      swallowtail,Papilio demodocus (Lepidoptera: Papilionidae) was found to contain
      methyl 3-hydroxybutanoate, 3-hydroxybutanoic acid, alpha-pinene, myrcene,
      limonene, beta-phellandrene, (Z)-ocimene, (E)-ocimene, beta-caryophyllene, (E)
      beta-farnesene, and germacrene-A, as well as a further number of unidentified
      sesquiterpenoid constituents. The presence of germacrene-A in the secretion was
      inferred from the formation of beta-elemene under certain GC conditions. Larvae
      of the second, third, and fourth instars produce qualitatively similar
      secretions. Remarkable quantitative differences were found between the secretions
      of individual larvae. These variations could not be correlated with the diet on
      which the larvae were fed, their sex, instar, or color form. However, in a number
      of larvae the two prongs of the osmeterium were found to produce quantitatively
      different secretions. 

PMID- 24310334
TI  - Mandibular gland secretions of two parasitoid wasps (Hymenoptera: Ichneumonidae).
AB  - Males ofRhyssa persuasoria andMegarhyssa nortoni nortoni exhibit marked
      aggregation behavior prior to and during the emergence of females from host
      trees, and this has been linked with the secretion of an odorous liquid from the
      mandibular glands. The volatile components of these secretions were examined by
      combined gas chromatography-mass spectrometry. While both species contained 6
      methylhept-5-en-2-one,M. nortoni nortoni was characterized by a series of alkyl
      spiroacetals andR. persuasoria contained 3-hydroxy-3-methylbutan-2-one. The same
      spiroacetals have previously been isolated from the mandibular glands of other
      Hymenoptera and have been directly associated with aggregation behavior in some
      species. The chemical and behavioral aspects of the two species are discussed. 

PMID- 24310335
TI  - Estimating maximum horizontal area of pheromone plumes.
AB  - Graphs and simple Gaussian plume equations are presented for estimating the
      maximum horizontal area within a pheromone plume. In its simplest form the area,A
      R , for a given scaling factor,R = Q/(Ku), isA R = AI R (beta), whereQ is the
      release rate,K is a specified concentration threshold,u is the wind velocity, and
      beta is an atmospheric stability index. Estimates ofA I and beta are given for
      several atmospheric stability typing schemes applicable to field and forest
      habitats. 

PMID- 24310336
TI  - Seed protein electrophoresis in taxonomic and evolutionary studies.
AB  - Seed protein electrophoresis is increasingly being utilized as an additional
      approach for species identification and as a useful tool for tracing back the
      evolution of various groups of plants. This paper summarizes the main features of
      the seed protein profile - stability, uniformity and additive nature. In
      addition, the significance of this approach for resolving specific taxonomic and
      evolutionary problems is pointed out. 

PMID- 24310337
TI  - Basic studies on hybrid wheat breeding : VIII. A new male sterility-fertility
      restoration system in common wheat utilizing the cytoplasms of Aegilops kotschyi
      and Ae. variabilis.
AB  - The nuclei of 12 common wheats (genome constitution AABBDD) were placed into the
      cytoplasms of Aegilops kotschyi and Ae. variabilis (both C(u)C(u)S(v)S(v)) by
      repeated backcrosses. Using these nucleus-cytoplasm hybrids, male sterility
      fertility restoration relationship was investigated. Male sterility was expressed
      by these cytoplasms only in Slm, Splt and Mch. The other nine common wheat nuclei
      gave normal fertility against these cytoplasms. These cytoplasms were compared
      with the Triticum timopheevi cytoplasm that is now widely used in the hybrid
      wheat breeding program in order to investigate their effects on important
      agronomic traits of the 12 common wheats: The kotschyi and variabilis cytoplasms
      were as good as the timopheevi cytoplasm in this respect.The F1 hybrid between
      (kotschyi)- or (variabilis)-Splt and CS showed normal fertility. Segregation of
      the fertiles and steriles in their F2 generations followed the simple Mendelian
      fashion, i.e., 3 fertile?1 sterile. Thus, the fertility restoration in this case
      is mainly controlled by a single dominant gene which will be designated as Rfv1.
      To determine its location, ditelo-lBS and -lBL of CS were crossed as male parents
      to male sterile (kotschyi)- and (variabilis)-Splt. The F1 hybrids between the
      male sterile Spit's and CS ditelo-lBS became male fertile, while those between
      the male sterile Spit's and CS ditelo-lBL became completely male sterile. Thus,
      the location of the gene Rfv1 has been determined to be on the short arm of
      chromosome lB of CS. Furthermore, a close relationship between the fertility
      restoring genes and the nucleolus organizer region was pointed out.Finally, the
      schemes of breeding the male sterile lines of a cultivar with these cytoplasms,
      and its maintainer line were formulated. The following two points were considered
      as the advantages of the present male sterility-fertility restoration system over
      that using the timopheevi cytoplasm in breeding hybrid wheat: (1) easier
      fertility restoration in F1 hybrids, and (2) no need of breeding the restorer
      line. 

PMID- 24310338
TI  - The allotetraploidization of maize : Part 2: The theoretical basis - the
      cytogenetics of segmental allotetraploids.
AB  - Allotetraploidization is the creation of artifical allotetraploids from a
      normally diploid species. The possible value of allotetraploid maize has been
      discussed in Section I of this series. Allotetraploidization of maize can be
      achieved by restructuring a maize genome so that its chromosomes will not pair
      with those of the standard maize genome. This restructuring can be done by
      concentrating differential pairing affinity (DPA) factors into a single line by a
      recurrent selection type of breeding program. Because the divergence of the maize
      genome is a gradual process, it is necessary to devise a model for chromosome
      pairing and gene segregation in segmental allotetraploids. This has been done by
      considering pairing in each arm separately and then combining paired arms to form
      pairing configurations for whole chromosomes. The chromosome disjunction patterns
      are hypothesized and genetic ratios in relation to different levels of DPA are
      suggested. 

PMID- 24310339
TI  - Effect of reciprocal crossing of selected lines of mice.
AB  - Mass selection of mice was conducted in populations of various size for 16
      generations. Each selected population (E) corresponded to an analogous unselected
      population (C). The experiment was conducted in three replicates. After the 16th
      generation the replicates of the selected and control lines were
      crossed.Reciprocal crossing within the control lines gave better results than
      reciprocal crossing of the selected lines, despite the fact that the selected
      mice were characterised by a higher inbreeding coefficient. Larger effects were
      also obtained when crossing smaller rather than larger populations. This result
      is understandable since the animals from the smaller populations were
      characterised by higher inbreeding coefficients.The effect of heterosis was
      higher upon crossing the control lines rather than the selected ones and this
      caused a decreased the response to selection in almost all the traits
      investigated. 

PMID- 24310340
TI  - Gene-centromere mapping by 4x-2x matings in potatoes.
AB  - Two of the four strands of a bivalent are recovered together in tetraploid
      progeny arising from 4x-2x matings. This provides a method for gene and
      centromere mapping. The cross pppp x Pp produced 62 nulliplex tetraploid
      individuals in a total of 951, i.e., 6.5%. The diploid clone was found to produce
      diplandrous gametes through first division restitution (FDR). The map distance P
      centromere was estimated as 13.0 units, the limiting values at the 95% binomial
      confidence interval being 10.1 and 16.3. The mapping method is explained in
      detail and a formula is deduced to obtain genotypic series of 2n gametes under
      particular assumptions. The direction 4x*2x is advantageous, since high seed set
      diploid clones which give 99% tetraploid progeny, and whose method of diplandroid
      formation is known are already available. Diploid clones heterozygous for many
      markers and tetraploids nulliplex for the same markers are needed to fully
      exploit this method. 

PMID- 24310341
TI  - Reproductive system and pattern of genetic variation in two Limnanthes species.
AB  - Several populations of two species of the genus Limnanthes, (L. alba, an
      outbreeder and L. floccosa, an inbreeder) were examined with respect to
      variability of fifteen quantitative characters, allozyme variation at 11 loci,
      and response to different pollination conditions and moisture stress. Nearly
      equal amounts of phenotypic variability were found in the two species. L. alba
      had higher within-family variability than L. floccosa, but this result was highly
      heterogeneous among characters. A study of between- and within-population
      variance estimates did not reject the null hypothesis that L. alba and L.
      floccosa are similar with regard to the partitioning and amount of variability
      for quantitative characters. However, allozyme variation at 11 loci in a large
      number of populations showed L. alba to be highly polymorphic in contrast to the
      virtual monomorphism within L. floccosa populations. The average number of
      alleles per locus in L. alba and L. floccosa was 1.97 and 1.02, respectively, and
      on an average, L. alba and L. floccosa populations had 63% and 3% loci with
      polymorphism, respectively. Three groups of allozyme allelic combinations emerged
      which correlated well with the taxonomic delineation of allogamous L. alba, three
      semi-autogamous L. floccosa forms and two autogamous L. floccosa forms.All taxa
      showed a significant reduction in the seed output per plant due to moisture
      stress. L. alba suffered a further loss of fecundity under the paucity of
      pollinators, L. floccosa ssp. floccosa showed no significant effect from this
      factor, whereas L. floccosa ssp. grandiflora exhibited a curvilinear response
      which peaked at 'partial pollination' and decreased to a lower level at 'full
      pollination.'The geographic distribution of the two species with regard to the
      temperature and rainfall distribution did not suggest L. floccosa to be living in
      drier marginal areas. Patterns of variation in flowering time showed L. alba to
      be less variable than L. floccosa. Overall, there seemed to be little direct
      support for the thesis that inbreeding species originated from outcrossing taxa
      in marginal environments as a direct adaptation to a shortened growing season of
      xeric environments and to the lack of pollinators. Alternative hypotheses suggest
      that autogamy in L. floccosa might have evolved as a reproductive isolating
      barrier acting through either cleistogamy or divergence in flowering times. 

PMID- 24310342
TI  - Identification of prognostic factors and the impact of palliative resection on
      survival of patients with stage IV hepatolithiasis-associated intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: Hepatolithiasis-associated intrahepatic cholangiocarcinoma (IHHCC)
      has a poor prognosis, because of lower curative resection rate when diagnosed in
      the advanced stage. There has been insufficient data regarding prognostic factors
      and the impact of palliative resection on its outcome. METHODS: A retrospective
      analysis of 78 eligible patients with stage IV IHHCC was performed. The potential
      prognostic factors were assessed by univariate and multivariate analyses.
      Patients were divided into groups A (margin positive) and B (nonresection) based
      on surgical methods. Demographic and operative data were compared. RESULTS: Of 78
      surgeries, R1 was achieved in 11, R2 in 21 and nonresection in 46 patients.
      Median overall survival (OS) of the entire cohort was 10.5 months. Surgery (P <
      0.01), tumor differentiation (P = 0.03), AJCC stage (P < 0.01), and serum CEA
      levels (P < 0.01) were independent prognostic factors. Significant differences
      were achieved in OS (P < 0.01), operation time (P < 0.01), estimated blood loss
      (P < 0.01), and postoperative complications (P = 0.02) between groups A and B.
      CONCLUSIONS: For patients with stage IV IHHCC, palliative resection is a rational
      and effective treatment. Normal serum CEA levels, higher tumor differentiation,
      and stage IVa predict good prognosis in stage IV IHHCC.

PMID- 24310344
TI  - Prevalence of extraforaminal nerve root compression below lumbosacral
      transitional vertebrae.
AB  - OBJECTIVE: Although pathology at the first mobile segment above a lumbosacral
      transitional vertebra (LSTV) is a known source of spinal symptoms, nerve root
      compression below an LSTV, has only sporadically been reported. Our objective was
      to assess the prevalence of nerve root entrapment below an LSTV, review the
      causes of entrapment, and correlate with presenting symptoms. MATERIALS AND
      METHODS: A retrospective review of MR and CT examinations of the lumbar spine was
      performed over a 5.5-year period in which the words "transitional vertebra" were
      mentioned in the report. Nerve root compression below an LSTV was assessed as
      well as the subtype of transitional vertebra. Correlation with clinical symptoms
      at referral was made. MR and CT examinations were also reviewed to exclude any
      other cause of symptoms above the LSTV. RESULTS: One hundred seventy-four
      patients were included in the study. Neural compression by new bone formation
      below an LSTV was demonstrated in 23 patients (13%). In all of these patients,
      there was a pseudarthrosis present on the side of compression due to partial
      sacralization with incomplete fusion. In three of these patients (13%), there was
      symptomatic correlation with no other cause of radiculopathy demonstrated. A
      further 13 patients (57%) had correlating symptoms that may in part be
      attributable to compression below an LSTV. CONCLUSIONS: Nerve root compression
      below an LSTV occurs with a prevalence of 13% and can be symptomatic in up to 70%
      of these patients. This region should therefore be carefully assessed in all
      symptomatic patients with an LSTV.

PMID- 24310345
TI  - A model for the expression of CaMV nucleic acid.
AB  - Analysis of the sequence of CaMV full-length 35S transcript reveals two features
      which may relate to the translation of open regions I-V. There is a region in the
      5' leader sequence which could act as a ribosome binding site. This is followed
      by a sequence, which is complementary to sequences which are found just upstream
      to the open regions. The singificance of these sequences is discussed. 

PMID- 24310343
TI  - Secondary analyses of the effects of lutein/zeaxanthin on age-related macular
      degeneration progression: AREDS2 report No. 3.
AB  - IMPORTANCE: The Age-Related Eye Disease Study (AREDS) formulation for the
      treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin
      E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2
      (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS
      formulation because of the demonstrated risk for lung cancer from beta carotene
      in smokers and former smokers and because lutein and zeaxanthin are important
      components in the retina. OBJECTIVE: To further examine the effect of
      lutein/zeaxanthin supplementation on progression to late AMD. DESIGN, SETTING,
      PARTICIPANTS: The Age-Related Eye Disease Study 2 is a multicenter, double-masked
      randomized trial of 4203 participants, aged 50 to 85 years, at risk for
      developing late AMD; 66% of patients had bilateral large drusen and 34% had large
      drusen and late AMD in 1 eye. INTERVENTIONS: In addition to taking the original
      or a variation of the AREDS supplement, participants were randomly assigned in a
      factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10
      mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the
      combination. MAIN OUTCOMES AND MEASURE: S Documented development of late AMD by
      central, masked grading of annual retinal photographs or by treatment history.
      RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the
      hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P =
      .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta
      carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for
      development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of
      neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central
      geographic atrophy. In analyses restricted to eyes with bilateral large drusen at
      baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed
      hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD,
      0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69
      1.39; P = .91) for central geographic atrophy. CONCLUSION AND RELEVANCE: The
      totality of evidence on beneficial and adverse effects from AREDS2 and other
      studies suggests that lutein/zeaxanthin could be more appropriate than beta
      carotene in the AREDS-type supplements. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00345176.

PMID- 24310346
TI  - Structure and rearrangements of rRNA genes in chloroplast DNA in two strains of
      Euglena gracilis.
AB  - The organisation of the rRNA genes in the chloroplast genomes of two strains of
      Euglena gracilis were analyzed and compared. It was previously shown that the
      bacillaris strain contains three complete rrn (rRNA) operons (7) and that the Z-S
      strain contains one operon (21). Using heteroduplex analysis it was found that
      the bacillaris strain contains, apart from the three complete rrn operons, an
      extra 16S rRNA gene, an extra partial 23S rRNA gene sequence and an inverted
      duplication of a stretch within the 5S-16S spacer. In addition a short (<100 bp)
      inverted repeat sequence (13) which forms a stem/loop structure in single
      stranded cpDNA was located between the 3'-end of the extra 16S rRNA gene and the
      partial 23 S rRNA sequence.The Z-S strain differs from the bacillaris strain by a
      deletion of two units of the complete rrn operons. The region upstream of the
      single complete rrn operon, including the inverted repeats, the partial 23S and
      the extra 16S rRNA sequences is identical with the bacillaris strain.The only non
      homology found in heteroduplexes between the SalI fragments of B of the two
      strains is the deletion-insertion loop which represents the two rrn operons. A
      small deletion loop was found occasionally in hetero-and in homoduplexes of both
      strands in the region of variable size. Apart from the deletion/insertion of two
      rrn operons the two genomes appear to be colinear as can be seen from partial
      denaturation mapping. The organisation of the rRNA genes of the two strains is
      compared with those of the Z strain and the bacillaris-ATCC strain. 

PMID- 24310347
TI  - Characterization and expression of chalcone synthase in different genotypes of
      Matthiola incana R.Br. during flower development.
AB  - The expression of the key enzyme of flavonoid biosynthesis, chalcone synthase
      (CHS), has been followed in different genotypes of Matthiola incana R.Br.
      (Brassicaceae) which are genetically defined with respect to anthocyanin
      production. Enzyme activity was determined by a radioactive assay in crude flower
      extracts. The amount of enzyme protein in the developing flower was determined by
      use of SDS-PAGE, protein blotting, reaction with an antiserum against CHS of
      parsley (Petroselinum hortense), and PAP staining. The molecular weight of about
      41 500 of the CHS subunits corresponds with that obtained from other higher
      plants. Steps of flower development were subdivided into stages-1,0, I-IV. During
      flower development of a Matthiola line with coloured petals (line 07) a defined
      pattern of CHS enzyme production can be observed: At the stage of bud opening
      (stage 0-I) a dramatic increase of the amount of CHS enzyme prodein in the petals
      occurs. This is quite different from results obtained with petals of the white
      flowering mutant line 18 bearing a genetic defect in the gene f coding for CHS.
      Here a reduced and nearly constant level of CHS enzyme protein can be observed
      during flower development. This line is most attractive for our studies of the
      regulation of enzyme synthesis because under stress conditions a slight colouring
      of the flower petals occurs, which is uniformly distributed and line-specific.
      This suggests that we are dealing with a CHS mutant producing a rather inactive
      enzyme protein at a low level. This protein may regain enzyme activity under
      certain environmental conditions. Preliminary investigations suggest a rather
      high level of CHS mRNA transcription at the bud opening stage of the flowers.
      Other white flowering mutant lines, line 17 (genotype ee) and line 19 (gg) with a
      late block in the flavonoid biosynthesis pathway, exhibit a concomitant reduction
      of CHS enzyme activity and protein content in comparison to anthocyanin-producing
      lines with the f(+)f(+)e(+)e(+)g(+)g(+)-genotype. 

PMID- 24310348
TI  - The ribosomal RNA genes from chloroplasts of mustard (Sinapis alba L.): mapping
      and sequencing of the leader region.
AB  - The genes coding for rRNAs from mustard chloroplasts were mapped within the
      inverted repeat regions of intact ctDNA and on ctDNA fragments cloned in pBR322.
      R-loop analysis and restriction endonuclease mapping show that the genes for 16S
      rRNA map at distances of 17 kb from the junctions of the repeat regions with the
      large unique region. The genes for 23S rRNA are located at distances of 2.8 kb
      from the junctions with the small unique region. Genes for 4.5S and 5S rRNA are
      located in close proximity to the 23S rRNA genes towards the small unique region.
      DNA sequencing of portions of the 5' terminal third from the mustard 16S rRNA
      gene shows 96-99% homology with the corresponding regions of the maize, tobacco
      and spinach chloroplast genes. Sequencing of the region proximal to the 16S rRNA
      gene reveals the presence of a tRNA(Val) gene in nearly the same position and
      with identical sequence as in maize, tobacco and spinach. Somewhat less but still
      strong homology is also observed for the tDNA (Val)/16S rDNA intercistronic
      regions and for the regions upstream of the tRNA(Val) gene. However, due to many
      small and also a few larger deletions and insertions in the leader region, common
      reading frames coding for homologous peptides larger than 44 amino acids can not
      be detected; it is therefore unlikely that this region contains a protein coding
      gene. 

PMID- 24310349
TI  - Insertion and deletion mutations within the nif region of Rhizobium japonicum.
AB  - Insertion and deletion mutants were used to characterize a genomic region of
      Rhizobium japonicum where the nitrogenase structural genes are located on two
      separate operons nifDK and nifH. In addition to previously described nifD:: Tn5
      and nifK:: Tn5 mutations we have now generated, by localized mutagenesis, further
      Tn5 insertion mutations in the vicinity of nifDK as well as within and adjacent
      to nifH. The nifD:: Tn5, nifK:: Tn5, and nifH:: Tn5 mutant strains were of the
      Nod(+) Fix(-) phenotype whereas all other mutants were symbiotically fully
      effective (Nod(+) Fix(+)). The nifH:: Tn5 mutation was helpful in the
      identification of the nifH gene product (the dinitrogenase reductase) by two
      dimensional gel electrophoresis: due to its polar effect this insertion
      specifically abolished the synthesis of that protein under microaerobic culture
      conditions. The ultrastructure of soybean root nodules infected with either the
      nif (+) wild-type or with the nif (-) (but otherwise isogenic) mutant strains was
      analyzed by electron microscopy. All contained fully developed bacteroids, but
      the nitrogen non-fixing mutants showed massive accumulation of PHB.Of Tn5
      containing strains, kanamycin sensitive derivatives were obtained which contained
      deletions. Several classes of deletion mutants were found which, as judged by
      their physical DNA structure and their phenotypes, allowed the following most
      important conclusions: (i) deletions lacking both the nifDK and nifH regions
      indicate linkage between the two operons whereby at least 15 kb of DNA separate
      them; (ii) one deletion ending upstream from nifH, and lacking only nifDK,
      indicates that the nifDK operon is located on the 5'-flanking side of the nifH
      operon; (iii) all deletion mutants are Nod(+) indicating that there are no
      essential nodulation gnes located between and adjacent to nifDK and nifH. 

PMID- 24310350
TI  - Transfer RNA genes of Euglena gracilis chloroplast DNA : A review.
AB  - Transfer RNA genes have been mapped to at least nine different loci on the
      physical map of the Euglena gracilis chloroplast genome. One of these loci in the
      ribosomal RNA operons is present three times per genome. The DNA sequences of six
      of the nine different loci, containing 21 different tRNA genes, have been
      determined. Genes corresponding to the amino acids Ala, Arg, Asn, Cys, Gln, Gly
      (2), Glu, His, Ile, Leu (2), Met (2), Phe, Ser, Thr, Trp, Tyr, Val, and one
      unassigned species have been identified. All genes except one are found in
      clusters of 2-6 genes. None of the known genes contains introns, nor codes for
      the 3'-CCA terminus. In addition to these genes, two pseudo tRNA genes are
      present in the rDNA leader region. 

PMID- 24310351
TI  - Molecular and genetic analysis of the chloroplast ATPase of chlamydomonas.
AB  - We have carried out a molecular and genetic analysis of the chloroplast ATPase in
      Chlamydomonas reinhardtii. Recombination and complementation studies on 16
      independently isolated chloroplast mutations affecting this complex demonstrated
      that they represent alleles in five distinct chloroplast genes. One of these
      five, the ac-u-c locus, has been positioned on the physical map of the
      chloroplast DNA by deletion mutations. The use of cloned spinach chloroplast
      ATPase genes in heterologous hybridizations to Chlamydomonas chloroplast DNA has
      allowed us to localize three or possibly four of the ATPase genes on the physical
      map. The beta and probably the epsilon subunit genes of Chlamydomonas CF1 lie
      within the same region of chloroplast DNA as the ac-u-c locus, while the alpha
      and proteolipid subunit genes appear to map adjacent to one another approximately
      20 kbp away. Unlike the arrangement in higher plants, these two pairs of genes
      are separated from each other by an inverted repeat. 

PMID- 24310353
TI  - Commentary on pancreatic carcinoma: the role of radiofrequency ablation in
      advanced disease.
AB  - Some comments about the role of ablation techniques in the management of advanced
      pancreatic cancer as palliative procedure. 

PMID- 24310352
TI  - Descriptive anatomy of Heschl's gyri in 430 healthy volunteers, including 198
      left-handers.
AB  - This study describes the gyrification patterns and surface areas of Heschl's
      gyrus (HG) in 430 healthy volunteers mapped with magnetic resonance imaging.
      Among the 232 right-handers, we found a large occurrence of duplication (64 %),
      especially on the right (49 vs. 37 % on the left). Partial duplication was twice
      more frequent on the left than complete duplication. On the opposite, in the
      right hemisphere, complete duplication was 10 % more frequent than partial
      duplication. The most frequent inter-hemispheric gyrification patterns were
      bilateral single HG (36 %) and left single-right duplication (27 %). The least
      common patterns were left duplication-right single (22 %) and bilateral
      duplication (15 %). Duplication was associated with decreased anterior HG surface
      area on the corresponding side, independently of the type of duplication, and
      increased total HG surface area (including the second gyrus). Inter-hemispheric
      gyrification patterns strongly influenced both anterior and total HG surface area
      asymmetries, leftward asymmetry of the anterior HG surface was observed in all
      patterns except double left HG, and total HG surface asymmetry favored the side
      of duplication. Compared to right-handers, the 198 left-handers exhibited lower
      occurrence of duplication, and larger right anterior HG surface and total HG
      surface areas. Left-handers' HG surface asymmetries were thus significantly
      different from those of right-handers, with a loss of leftward asymmetry of their
      anterior HG surface, and with significant rightward asymmetry of their total HG
      surface. In summary, gyrification patterns have a strong impact on HG surface and
      asymmetry. The observed reduced lateralization of HG duplications and anterior HG
      asymmetry in left-handers highlights HG inter-hemispheric gyrification patterns
      as a potential candidate marker of speech lateralization. 

PMID- 24310354
TI  - Does ablation technique utilized in the management of unresectable locally
      advanced pancreatic adenocarcinoma?
AB  - Radiofrequency ablation in the management of advanced pancreatic cancer should be
      no longer utilized in patients with locally advanced or metastatic pancreatic
      adenocarcinoma. 

PMID- 24310355
TI  - Tumor acidity as evolutionary spite.
AB  - Most cancer cells shift their metabolic pathway from a metabolism reflecting the
      Pasteur-effect into one reflecting the Warburg-effect. This shift creates an
      acidic microenvironment around the tumor and becomes the driving force for a
      positive carcinogenesis feedback loop. As a consequence of tumor acidity, the
      tumor microenvironment encourages a selection of certain cell phenotypes that are
      able to survive in this caustic environment to the detriment of other cell types.
      This selection can be described by a process which can be modeled upon spite: the
      tumor cells reduce their own fitness by making an acidic environment, but this
      reduces the fitness of their competitors to an even greater extent. Moreover, the
      environment is an important dimension that further drives this spite process.
      Thus, diminishing the selective environment most probably interferes with the
      spite process. Such interference has been recently utilized in cancer treatment. 

PMID- 24310356
TI  - Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution
      process (Dismantling of Multicellularity).
AB  - Carcinogenesis occurs through a series of steps from normal into benign and
      finally malignant phenotype. This cancer evolutionary trajectory has been
      accompanied by similar metabolic transformation from normal metabolism into
      Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism
      and/or Lactate-Symbiosis. Due to lactate production as an end-product of
      glycolysis, tumor colonies acquire new phenotypes that rely on lactate as
      energetic fuel. Presence of Warburg-Effect indicates that some tumor cells
      undergo partial (if not complete) de-endosymbiosis and so cancer cells have been
      become unicellular microorganism (anti-Dollo's Law) specially when they evolve to
      develop cannibalism as way of metabolism while oxidative types of cells that rely
      on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus,
      at the end, the cancer colony could be considered as integrated metabolic
      ecosystem. Proper understanding of tumor metabolism will contribute to discover
      potential anticancer agents besides conventional chemotherapy. 

PMID- 24310357
TI  - A Comment on Qi et al.: An Estimation of Radiobiological Parameters for Head-and
      Neck and the Clinical Implications. Cancers, 2012, 4, 566-580.
AB  - Important results were shown as cell survival points in the two panels of the
      figure which is reproduced in this Comment letter. A curve was fitted assuming
      the mono-exponential recovery half-time of 17 +/- 21 minutes. The wide error
      limits indicate that this fit is not very good, but the notable feature of both
      panels is that the last four points are clearly continuing to rise, above the
      "fitted" curve. This indicates that there is a second, slower, component of
      repair or recovery and this Comment explores constructively the implications of
      that additional discovery. 

PMID- 24310358
TI  - Cancer cachexia: muscle physiology and exercise training.
AB  - Cachexia in cancer patients is a condition marked by severe tissue wasting and a
      myriad of quality of life and health consequences. Cachexia is also directly
      linked to the issues of morbidity and survivability in cancer patients.
      Therapeutic means of mitigating cachexia and its effects are thus critical in
      cancer patient treatment. We present a discussion on the use of physical exercise
      activities in the context of such treatment as a means to disruption the tissue
      wasting effects (i.e., muscle tissue losses via anorexigenic pro-inflammatory
      cytokines) of cachexia. In addition we propose a theoretical model (Exercise Anti
      Cachectic Hypothetical-"EACH" model) as to how exercise training may promote a
      disruption in the cycle of events leading to advancing cachexia and in turn
      promote an enhanced functionality and thus improved quality of life in cancer
      patients. 

PMID- 24310359
TI  - Increasing melanoma-too many skin cell damages or too few repairs?
AB  - Skin melanoma rates have been increasing for a long time in many Western
      countries. The object of this study was to apply modern problem-solving theory
      normally used to clear industrial problems to search for roots and causes of this
      medical question. Increasing cancer rates can be due to too many cell damage
      incidents or to too few repairs. So far, it has been assumed that the melanoma
      epidemic mainly is caused by increasing sun tanning habits. In order to explore
      this problem in more detail, we used cancer statistics from several countries
      over time and space. Detailed analysis of data obtained and a model study to
      evaluate the effects from increased damages or decreased repairs clearly indicate
      that the main reason behind the melanoma problem is a disturbed immune system.
      The possibility to introduce efficient corrective actions is apparent. 

PMID- 24310360
TI  - A simple, rapid and sensitive UFLC-MS/MS method for the quantification of oral
      contraceptive norgestrel in human plasma and its pharmacokinetic applications.
AB  - A simple, rapid and sensitive ultra flow liquid chromatography-tandem mass
      spectrometry (UFLC-MS/MS) assay for the determination of norgestrel in human
      plasma was developed using levonorgestrel D6 as an internal standard (IS).
      Norgestrel and IS were extracted from human plasma via liquid-liquid extraction.
      Chromatographic separation was achieved on a Zorbax XDB-Phenyl column under
      isocratic conditions. Detection was done by tandem mass spectrometry, operating
      in positive ion mode. The protonated precursor to product ion transitions
      monitored for norgestrel and IS were at m/z 313.30->245.40 and 319.00->251.30
      respectively. The method was fully validated as per current regulatory
      guidelines. Anticoagulant counter ion effect was also assessed with K2EDTA and
      K3EDTA. The method was validated with a linearity range of 304.356-50 807.337
      pg/mL having run time of 2.0 min per sample. The method has shown tremendous
      reproducibility with intra- and inter-day precision (%CV) less than 11.0% and
      intra- and inter-day accuracy less than 9.0% of nominal values. The validated
      method was applied to a pharmacokinetic study in human plasma samples generated
      after administrating a single oral dose of 0.3 mg norgestrel tablets to healthy
      female volunteers and has proved to be highly reliable for the analysis of
      clinical samples.

PMID- 24310361
TI  - Gd3+-DTPA-bis (N-methylamine) - anionic linear globular Dendrimer-G1; a more
      efficient MRI contrast media.
AB  - By advancing of molecular imaging techniques, magnetic resonance imaging (MRI) is
      becoming an increasingly important tool in early diagnosis. Researchers have
      found new ways to increase contrast of MRI images.Therefore some types of drug
      known as contrast media are produced. Contrast media improve the visibility of
      internal body structures in MRI images. Gadodiamide (Omniscan(r)) is one of these
      contrast media which is produced commercially and used clinically. In this study
      Gadodiamide was first synthesized and then qualitative and quantitative methods
      were carried out to ensure the proper synthesis of this drug then to increase the
      efficiency of this contrast medium use dendrimer that is one kind of nano
      particle. This dendrimer has a polyethylene glycol (PEG) core and citric acid
      branches. After dendrimer attached to Gadodiamide to ensure the proper efficient
      connection between them the stability studies were carried out and cytotoxicity
      of the drug was evaluated. Finally, after ensuring the non-toxicity of the drug,
      in vivo studies (injected into mice) MR imaging was performed to examine the
      impact of synthesis drug on the resolution of image.The result obtained from this
      study demonstrated that the attachment of Gadodiamide to dendrimer reduces its
      cytotoxicity and also improved resolution of image. Also the new contrast media
      (Gd3+-DTPA- bis [N-methylamine] - Dendrimer) - unlike Omniscan(r) - is
      biodegradable and able to enter the HEPG2 cell line. The results confirm the
      hypothesis that using dendrimer to synthesize this new nano contrast medium
      increases its effectiveness.

PMID- 24310362
TI  - A liquid chromatography tandem mass spectrometry based regulatory compliant
      method for the determination of tenofovir in human serum.
AB  - A simple, rapid, and specific assay based on solid phase extraction and liquid
      chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS-MS)
      for the quantitative analysis of Tenofovir in human serum using Tenofovir D6 as
      internal standard (IS) have been developed. The precursor to product ion
      transitions of m/z 288.2/176.2 and m/z 293.9/182.3 used to measure the analyte
      and internal standard (Tenofovir and Tenofovir D6). The method was validated over
      a concentration range of 5.06-603.72 ng mL(-1). The method was validated over the
      parameters like selectivity, matrix effect, sensitivity, linearity, precision,
      accuracy, various stabilities (bench top stability, standard stock solution
      stability in refrigerator and at room temperature, stock dilution stability, auto
      sampler stability, freeze thaw stability, long term stability - 65 degrees C+/-10
      degrees C & long term stability - 22 degrees C+/-5 degrees C, reagent stability,
      dry extract stability, wet extract stability in refrigerator and at bench top,
      blood stability), effect of potentially interfering drugs, dilution integrity,
      recovery and reinjection reproducibility. The mean % recovery of Tenofovir was
      98.22% with a precision of 2.42%, The mean % recovery of Tenofovir D6 was 100.96%
      with a precision of 2.88%. The RSD % of intra-day and inter-day assay was<=15%. 

PMID- 24310363
TI  - Validated stability-indicating assay method for simultaneous determination of
      aceclofenac and thiocolchicoside using RP-HPLC.
AB  - A rapid, accurate, precise, robust and specific stability indicating RP-HPLC
      method has been developed and validated for simultaneous determination of fixed
      dose combination of Aceclofenac (ACF) and Thiocolchicoside (THC). Combinations
      and marketed tablets were subjected to stress conditions such as oxidation,
      hydrolysis, photolysis and heat. Successful separation of drugs from stress
      degradation products was achieved on Kromasil C18 (250 * 4.6 mm, 5 MUm) column at
      30  degrees C using gradient mobile phase system consisting of (A) 10 mM ammonium
      acetate pH 5.00 buffer and (B) acetonitrile: water (70:30 v/v). The flow rate was
      1.0 mL/min with UV detection at 265 nm. The retention time of THC and ACF was
      13.29 and 22.20 min respectively. Peak purity of both the drugs was passing in
      all degradation conditions demonstrates the specificity of assay method for their
      estimation in presence of degradation products. The developed HPLC method was
      validated for linearity, accuracy, precision and robustness. The linearity of the
      proposed method was investigated in the range of 80-280 ug/mL for ACF and 6.4
      22.4 ug/mL for THC. The utility of the procedure was verified by its application
      to marketed formulations.

PMID- 24310364
TI  - Invited comment on Bishawi et al.: surgical site infection rates: open versus
      hand-assisted colorectal resections.

PMID- 24310365
TI  - GIS based mapping of land cover changes utilizing multi-temporal remotely sensed
      image data in Lake Hawassa Watershed, Ethiopia.
AB  - Classifying multi-temporal image data to produce thematic maps and quantify land
      cover changes is one of the most common applications of remote sensing. Mapping
      land cover changes at the regional level is essential for a wide range of
      applications including land use planning, decision making, land cover database
      generation, and as a source of information for sustainable management of natural
      resources. Land cover changes in Lake Hawassa Watershed, Southern Ethiopia, were
      investigated using Landsat MSS image data of 1973, and Landsat TM images of 1985,
      1995, and 2011, covering a period of nearly four decades. Each image was
      partitioned in a GIS environment, and classified using an unsupervised algorithm
      followed by a supervised classification method. A hybrid approach was employed in
      order to reduce spectral confusion due to high variability of land cover.
      Classification of satellite image data was performed integrating field data,
      aerial photographs, topographical maps, medium resolution satellite image (SPOT
      20 m), and visual image interpretation. The image data were classified into nine
      land cover types: water, built-up, cropland, woody vegetation, forest, grassland,
      swamp, bare land, and scrub. The overall accuracy of the LULC maps ranged from
      82.5 to 85.0 %. The achieved accuracies were reasonable, and the observed
      classification errors were attributable to coarse spatial resolution and pixels
      containing a mixture of cover types. Land cover change statistics were extracted
      and tabulated using the ERDAS Imagine software. The results indicated an increase
      in built-up area, cropland, and bare land areas, and a reduction in the six other
      land cover classes. Predominant land cover is cropland changing from 43.6 % in
      1973 to 56.4 % in 2011. A significant portion of land cover was converted into
      cropland. Woody vegetation and forest cover which occupied 21.0 and 10.3 % in
      1973, respectively, diminished to 13.6 and 5.6 % in 2011. The change in water
      body was very peculiar in that the area of Lake Hawassa increased from 91.9 km(2)
      in 1973 to 95.2 km(2) in 2011, while that of Lake Cheleleka whose area was 11.3
      km(2) in 1973 totally vanished in 2011 and transformed into mud-flat and grass
      dominated swamp. The "change and no change" analysis revealed that more than one
      third (548.0 km(2)) of the total area was exposed to change between 1973 and
      2011. This study was useful in identifying the major land cover changes, and the
      analysis pursued provided a valuable insight into the ongoing changes in the area
      under investigation. 

PMID- 24310366
TI  - Soil criteria to protect terrestrial wildlife and open-range livestock from metal
      toxicity at mining sites.
AB  - Thousands of hard rock mines exist in the western USA and in other parts of the
      world as a result of historic and current gold, silver, lead, and mercury mining.
      Many of these sites in the USA are on public lands. Typical mine waste associated
      with these sites are tailings and waste rock dumps that may be used by wildlife
      and open-range livestock. This report provides wildlife screening criteria levels
      for metals in soil and mine waste to evaluate risk and to determine the need for
      site-specific risk assessment, remediation, or a change in management practices.
      The screening levels are calculated from toxicity reference values based on
      maximum tolerable levels of metals in feed, on soil and plant ingestion rates,
      and on soil to plant uptake factors for a variety of receptors. The metals chosen
      for this report are common toxic metals found at mining sites: arsenic, cadmium,
      copper, lead, mercury, and zinc. The resulting soil screening values are well
      above those developed by the US Environmental Protection Agency. The difference
      in values was mainly a result of using toxicity reference values that were more
      specific to the receptors addressed rather than the most sensitive receptor. 

PMID- 24310367
TI  - Water pollution of Sabarmati River--a harbinger to potential disaster.
AB  - River Sabarmati is one of the biggest and major river of Gujarat that runs
      through two major cities of Gujarat, Gandhinagar and Ahmedabad and finally meets
      the Gulf of Khambhat (GoK) in the Arabian Sea. A study was conducted to evaluate
      the water quality of this river, as it could possibly be one of the major sources
      for filling up Kalpasar, the proposed man-made freshwater reservoir supposed to
      be the biggest one in the world. A total of nine sampling stations were
      established covering 163 km stretch of the river from upstream of Gandhinagar
      city to Vataman near Sabarmati estuary. Physicochemical (temprature, pH,
      salinity, chloride, total dissolved solids, turbidity, dissolved oxygen,
      biochemical oxygen demand, phenol, and petroleum hydrocarbons), biological
      (phytoplankton), and microbiological (total and selective bacterial count)
      analyses indicated that the river stretch from Ahmedabad-Vasana barriage to
      Vataman was highly polluted due to perennial waste discharges mainly from
      municipal drainage and industries. An implementation of sustainable management
      plan with proper treatment of both municipal and industrial effluents is
      essential to prevent further deterioration of the water quality of this river.

PMID- 24310368
TI  - Development of a new risk-based framework to guide investment in water quality
      monitoring.
AB  - An innovative framework for optimising investments in water quality monitoring
      has been developed for use by water and environmental agencies. By utilising
      historical data, investigating the accuracy of monitoring methods and considering
      the risk tolerance of the management agency, this new methodology calculates
      optimum water quality monitoring frequencies for individual water bodies. Such
      information can be applied to water quality constituents of concern in both
      engineered and natural water bodies and will guide the investment of monitoring
      resources. Here we present both the development of the framework itself and a
      proof of concept by applying it to the occurrence of hazardous cyanobacterial
      blooms in freshwater lakes. This application to existing data demonstrates the
      robustness of the approach and the capacity of the framework to optimise the
      allocation of both monitoring and mitigation resources. When applied to
      cyanobacterial blooms in the Swan Coastal Plain of Western Australia, we
      determined that optimising the monitoring regime at individual lakes could
      greatly alter the overall monitoring schedule for the region, rendering it more
      risk averse without increasing the amount of monitoring resources required. For
      water resources with high-density temporal data related to constituents of
      concern, a similar reduction in risk may be observed by applying the framework. 

PMID- 24310369
TI  - Evaluating soil quality under a long-term integrated tillage-water-nutrient
      experiment with intensive rice-wheat rotation in a semi-arid Inceptisol, India.
AB  - Long-term sustainability and a declining trend in productivity of rice-wheat
      rotation in the Indo-Gangetic plain, often direct towards the changes in soil
      quality parameters. Soil quality is decided through few sensitive soil physical,
      chemical and biological indicators as it cannot be measured directly. The present
      investigation was carried out to develop a valid soil quality index through some
      chosen indicators under long-term influences of tillage, water and nutrient
      management practices in a rice-wheat cropping system. The experiment consisted of
      two tillage treatments, three irrigation treatments, and nine nutrient management
      treatments for both rice and wheat, was continued for 8 years. The index was
      developed using expert-opinion based conceptual framework model. After harvest of
      rice, the CFSQI-P (productivity) was higher under puddled situation, whereas
      CFSQI-EP (environmental protection) was more under non-puddled condition and 3
      days of drainage was found promising for all the indices. No-tillage practice
      always showed higher soil quality index. The treatments either receiving full
      organics (100% N) or 25% substitution of fertilizer N with organics showed higher
      soil quality indices. Puddling, irrigation after 3 days of drainage and
      substitution of 25% recommended fertilizer N dose with FYM in rice could be
      practiced for maintaining or enhancing soil quality. No-tillage, two irrigations,
      and domestic sewage sludge in wheat can safely be recommended for achieving
      higher soil quality.

PMID- 24310370
TI  - Structure of a uranyl peroxo complex in aqueous solution from first-principles
      molecular dynamics simulations.
AB  - Static ab initio and density-functional computations, as well as Car-Parrinello
      molecular dynamics simulations in aqueous solution are reported for
      [UO2(OH)(kappa(2)-O2)(H2O)2](-) and [UO2(OH)2(kappa(1)-O2H)(H2O)](-). Whereas the
      kappa(1)-hydroperoxo isomer is found to be more stable than the kappa(2)-peroxo
      form in the gas phase, the order of stability is reversed in explicit bulk
      solution. Based on free energies from thermodynamic integration (BLYP
      functional), the peroxo form is favoured by ca. 32 kJ mol(-1) in water. This
      stabilisation is discussed in terms of the hydration shells about the individual
      ligands and dipole moments of the complexes in water, and highlights the
      importance of explicit solute-solvent interactions and bulk solvation for the
      speciation of uranyl(vi) compounds. 

PMID- 24310372
TI  - A sodium-enabled 'Pourbaix sensor': a three-input AND logic gate as a 'lab-on-a
      molecule' for monitoring Na+, pH and pE.
AB  - A novel supramolecular three-input AND logic gate is demonstrated as a 'lab-on-a
      molecule' for monitoring the Na(+), pH and pE levels in solution by communicating
      a fluorescence signal. The fluorescence signal is modulated by three photoinduced
      electron transfer reactions that are controlled by an unprecedented combination
      of two cation binding events and one redox reaction. 

PMID- 24310371
TI  - Bacterial RNA motif in the 5' UTR of rpsF interacts with an S6:S18 complex.
AB  - Approximately half the transcripts encoding ribosomal proteins in Escherichia
      coli include a structured RNA motif that interacts with a specific ribosomal
      protein to inhibit gene expression, thus allowing stoichiometric production of
      ribosome components. However, many of these RNA structures are not widely
      distributed across bacterial phyla. It is increasingly common for RNA motifs
      associated with ribosomal protein genes to be identified using comparative
      genomic methods, yet these are rarely experimentally validated. In this work, we
      characterize one such motif that precedes operons containing rpsF and rpsR, which
      encode ribosomal proteins S6 and S18. This RNA structure is widely distributed
      across many phyla of bacteria despite differences within the downstream operon,
      and examples are present in both E. coli and Bacillus subtilis. We demonstrate a
      direct interaction between an example of the RNA from B. subtilis and an S6:S18
      complex using in vitro binding assays, verify our predicted secondary structure,
      and identify a putative protein-binding site. The proposed binding site bears a
      strong resemblance to the S18 binding site within the 16S rRNA, suggesting
      molecular mimicry. This interaction is a valuable addition to the canon of
      ribosomal protein mRNA interactions. This work shows how experimental
      verification translates computational results into concrete knowledge of
      biological systems. 

PMID- 24310373
TI  - Cataract surgery: our ongoing voyage to the promised land.

PMID- 24310374
TI  - 2013 update on the management of posterior capsular rupture during cataract
      surgery.
AB  - PURPOSE OF REVIEW: Posterior capsular rupture (PCR) is an infrequent complication
      of cataract surgery that can lead to significant ocular morbidity and permanent
      vision loss. In the setting of PCR, the primary objective is the safe and
      thorough evacuation of vitreous and lens fragments from the anterior segment. The
      secondary objective is the stable placement of an intraocular lens (IOL) selected
      for best refractive outcomes. Expedited referral to vitreoretinal specialists is
      recommended for management of posteriorly dislocated lens material and
      surveillance for retinal injury. It is the intention of this review to present
      current guidelines for the management of PCR. RECENT FINDINGS: There are new
      techniques available to anterior and posterior segment surgeons in the setting of
      PCR. Endoillumination may facilitate visualization during anterior vitrectomy and
      the IOL may be used as a pupillary barrier to prevent loss of lens fragments.
      When secondary procedures are needed, early return to the operating room and
      small-gauge pars plana techniques may reduce patient morbidity. SUMMARY: When
      approached carefully and systematically, patients may have good outcomes in the
      setting of PCR. Recent advancements in instrumentation and technique encourage
      further study and may lead to new standards of care.

PMID- 24310375
TI  - The business of refractive laser assisted cataract surgery (ReLACS).
AB  - PURPOSE OF REVIEW: Refractive Laser Assisted Cataract Surgery (ReLACS) combines
      the femtosecond laser with other noncovered tests and services in an attempt to
      reduce spectacle dependence in combination with cataract surgery. Significant
      interest is present among ophthalmologists who are considering adopting this
      technology, however significant capital outlays and continuing expenses can make
      the decision to adopt ReLACS foreboding. We review the financial considerations
      of ReLACS and review the trends seen in early adopters of this technology. RECENT
      FINDINGS: Recent findings have shown that ReLACS is a growing segment of cataract
      surgery. Most practices who have implemented the technology have broken even and
      have a positive outlook on the financial return of implementing the ReLACS
      program. The average break-even analysis point for practices is around 230 cases
      a year. SUMMARY: ReLACS is growing and appears to be a financial viable approach
      for many practices.

PMID- 24310376
TI  - Femtosecond laser assisted cataract surgery followed by coaxial
      phacoemulsification or microincisional cataract surgery: differences and
      advantages.
AB  - PURPOSE OF REVIEW: This review outlines the advantages and the differences of
      femtosecond laser-assisted cataract surgery (FLACS) following a coaxial or
      microincision cataract surgery phacoemulsification in the surgical outcome and
      greater control of cataract surgery. RECENT FINDINGS: FLACS offers minimal tissue
      damage and extreme precision during corneal incision creation, continuous
      circular capsulorhexis (CCC) and nuclear fragmentation. It also allows
      diminishing the mean average ultrasound power to emulsify the nucleus followed by
      a coaxial or a biaxial procedure. The impact of reduced phacoemulsification
      energy on the corneal endothelium is an interesting topic that is being
      investigated. Despite its benefits, this technology has relevant financial issues
      and a high learning curve. SUMMARY: FemtoMICS appears to be surgically and
      statistically more efficient than the FemtoCoaxial technique and Femtoincisions
      prove to be stable and do not change the corneal high order aberration
      significantly with favorable results of the triplanar configuration.

PMID- 24310377
TI  - Severe forms of schistosomiasis mansoni: epidemiologic and economic impact in
      Brazil, 2010.
AB  - BACKGROUND: Schistosoma mansoni infection is generally asymptomatic at the
      initial stage. However, patients left untreated can develop severe, potentially
      fatal clinical disease. In Brazil, S. mansoni transmission occurs in 19 states
      and, despite the contribution of infection to the cycle of poverty and disease,
      the economic impact of severe cases is unclear. Our objectives were to estimate
      the epidemiological burden and the costs of severe stages of S. mansoni in Brazil
      in 2010. METHODS: We conducted an epidemiologic descriptive study and a partial
      economic evaluation of cost-of-illness. The study population was identified from
      records of notifications, hospitalizations and deaths related to S. mansoni in
      the respective information systems. RESULTS: The mortality rate for S. mansoni
      was 0.3 deaths per 100 000 population, which represented 1.1% of the deaths in
      Brazil from infectious diseases listed in Chapter I of the International
      Statistical Classification of Disease and Related Health Problems, 10(th)
      revision (ICD 10), and almost 9.0% of deaths from infection diseases in the state
      of Pernambuco. We calculated 6419 potential years of life lost (PYLL) to S.
      mansoni. The costs estimated within the public health sector totaled R$889 049.58
      (US$495 016.47) and the costs of productivity losses reached R$ 35 725 332.72
      (US$ 19 891 590.86) in terms of salaries lost as a result of premature death or
      absence from work. The cost-of-illness related to S. mansoni in Brazil was R$ 36
      614 382.30 (US$ 20 386 627.12). CONCLUSION: The severe cases of S. mansoni
      disease still occurring in Brazil have an important epidemiologic and economic
      impact, representing a significant loss for society. The development of severe
      cases of a neglected parasitic disease that is preventable and responsive to
      primary healthcare intervention should be considered an expression of inequity.
      Our findings provide important evidence to support the strengthening of public
      health measures and investment to reduce poverty-related diseases in Brazil
      today.

PMID- 24310378
TI  - An economic analysis of money follows the patient.
AB  - INTRODUCTION: As part of the proposed changes to re-design the Irish health-care
      system, the Department of Health (money follows the patient-policy paper on
      hospital financing, 2013b) outlined a new funding model for Irish hospitals-money
      follows the patient (MFTP). This will replace the existing system which is
      predominately prospective with hospitals receiving a block grant per annum. MFTP
      will fund episodes of care rather than hospitals. Thus, hospital revenue will be
      directly linked to activity [activity-based funding (ABF)]. THEORY AND LITERATURE
      REVIEW: With ABF there is a fundamental shift to a system where hospitals
      generate their own income and this changes incentive structures. While some of
      these incentives are intended (reducing cost per case and increasing coding
      quality), others are less intended and less desirable. As a result, there may be
      reductions in quality, upcoding, cream skimming and increased pressure on other
      parts of the health system. In addition, MFTP may distort health system
      priorities. There are some feasibility concerns associated with the
      implementation of MFTP. Data collection, coding and classification capacity are
      crucial for its success. While MFTP can build on existing systems, significant
      investment is required for its success. This includes investment in coding and
      classification, infrastructure, skills, IT, contracting, commissioning, auditing
      and performance monitoring systems. CONCLUSIONS: Despite the challenges facing
      implementers, MFTP could greatly improve the transparency and accountability of
      the system. Thus if the downside risks are managed, there is potential for MFTP
      to confer significant benefits to Irish hospital care.

PMID- 24310379
TI  - Access of large and nonvolatile molecules to the vomeronasal organ of mammals
      during social and feeding behaviors.
AB  - The vomeronasal organ, a chemosensory structure in the nasal cavity, is important
      in the detection of mammalian chemosignals, many of which are thought to be large
      molecules having low volatility. We conducted a series of experiments to
      determine whether nonvolatile molecules enter the vomeronasal organ during a
      variety of behavioral contexts in five species. We found that a nonvolatile dye
      entered the vomeronasal organ during investigation of urine from conspecific
      donors (experiment 1), during investigation of urine from heterospecific donors
      (experiment 2), during self-grooming (experiment 3), and during social grooming
      (experiment 4). In other experiments, we determined that nonvolatile molecules
      entered the vomeronasal organ during consumatory behaviors. Animals that ate a
      dye-adulterated familiar food had the nonvolatile marker in their vomeronasal
      organs (experiment 5). Animals that drank either familiar or novel dye
      adulterated solutions also had the nonvolatile marker in their vomeronasal organs
      (experiment 6). In Experiment 7, large (66,000-dalton) fluorescent molecules were
      mixed with female urine which was then presented to male animals. We observed
      that the large molecules were transported to the vomeronasal organ. In the final
      experiment, we determined that mere contact between the snout of a dead animal
      and the stimulus resulted in transport of nonvolatile substances to the
      vomeronasal organ. We conclude that the vomeronasal organ, like the olfactory
      epithelium, is in continuous contact with the environment, but unlike the
      olfactory epithelium, the sensory receptors of the vomeronasal organ interact
      with molecules of low volatility, in addition to more volatile odorants. 

PMID- 24310380
TI  - Flavonoid pigments in marbled white butterfly (Melanargia galathea) are dependent
      on flavonoid content of larval diet.
AB  - Analyses of two-dimensional chromatographic flavonoid patterns of butterflies
      reared on different grass species have shown that the flavonoid pattern
      ofMelanargia galathea is dependent on the flavonoid content of the larval diet.
      This confirms the dietary origin of flavonoid pigments inM. galathea. The
      flavonoid patterns of butterflies reared on different grass species differ from
      each other and from the larval food plants;M. galathea reared on the same grass
      species have identical flavonoid patterns. Differences in the butterfly and
      larval food plant flavonoid patterns indicate that the ingested flavonoids are
      metabolized byM. galathea or its gut flora before sequestration. The distinct
      flavonoid patterns of butterflies reared on different larval food plants have
      been defined as the flavonoid fingerprint profiles for each grass species.
      Similarity between theFestuca rubra flavonoid fingerprint profile and the
      constant flavonoid pattern characteristic of wild-capturedMelanargia suggests
      thatMelanargia larvae are not generalist grass feeders, but are specific toF.
      rubra or toF. rubra and a few closely related grass species in the wild. 

PMID- 24310381
TI  - Individual variation in the pheromone of the turnip moth,Agrotis segetum.
AB  - Female turnip moths (Agrotis segetum) from a laboratory culture inbred for more
      than 30 generations, and the offspring (first and third generation) from field
      collected insects were analyzed individually for acetates and alcohols in the
      pheromone gland. Quantitative analysis of individual components was performed at
      the subnanogram level by gas chromatographymass spectrometry (selected ion
      monitoring). The titer of the pheromone, i.e., the sum of the homologous acetates
      (Z)-5-decenyl acetate, (Z)-7-dodecenyl acetate, and (Z)-9-tetradecenyl acetate
      was 2.0 +/- 0.3 ng in the laboratory culture and 3.2 +/- 0.6 ng in the "wild
      strain." There was no correlation between pheromone titer and female weight. The
      relative proportion of the pheromone components varied substantially between
      individuals, but there was no statistically significant difference between the
      two populations. The percentages of the respective compounds (-X +/- coefficient
      of variation) were 14.8 +/- 127% for Z5-10:OAc, 55.6 +/- 32% for Z7-12:OAc, and
      29.6 +/- 59% forZ9-14:OAc. The pheromone composition varied more in the wild
      strain than in the laboratory culture. The significance of the pheromone
      variation to the attraction of males was tested in a field experiment. The ratio
      of males trapped by the most attractive blend versus the least attractive one was
      2.2. 

PMID- 24310382
TI  - Ester components of aggregation pheromone ofDrosophila virilis (Diptera:
      Drosophilidae).
AB  - The male-produced aggregation pheromone ofDrosophila virilis was found to contain
      five ester components, in addition to a previously identified hydrocarbon, (Z)-10
      heneicosene (Z10-21). The five esters were: the methyl, ethyl, and 1-methylethyl
      (isopropyl) esters of 2-methyl-(E)-2-butenoic (tiglic) acid and the methyl and
      ethyl esters of hexanoic acid. The esters were not detected in females. Each
      ester was active by itself in laboratory bioassay tests, and each increased the
      number of flies responding toZ10-21 ca. 4-5 times. In comparisons among the five
      esters at 10 ng per compound, ethyl tiglate was the most active, and methyl
      tiglate, the least. No mixture of esters was found to be significantly more
      active than ethyl tiglate alone. In a doseresponse study, bioassay activity
      increased with dose for both ethyl tiglate andZ10-21. Newly emerged males did not
      have detectable levels of the esters. All five esters increased as sexual
      maturity was approached. Ethyl tiglate and ethyl hexanoate were the most abundant
      in mature males, usually over 15 ng per individual. Ratios among the esters were
      variable. Male flies also contained an as yet unidentified attractant(s) still
      more polar than the esters, which was synergistic with the esters and
      hydrocarbon. Food odors also synergized the synthetic compounds. 

PMID- 24310383
TI  - Behavioral responses of male turnip moths,Agrotis segetum, to sex pheromone in a
      flight tunnel and in the field.
AB  - The response of individual male turnip mothsAgrotis segetum was observed in a
      sustained flight tunnel to a mixture of decyl acetate, (Z)-5-decenyl acetate, (Z)
      7-dodecenyl acetate, and (Z)-9-tetradecenyl acetate in proportions similar to
      those found in gland extracts from virgin females (0.6: 1:5:2.5). Lures
      containing 3-30 MUg (Z)-5-decenyl acetate proved to be maximally attractive, with
      approximately 60% of the males completing all behavioral steps from activation to
      copulation efforts. A 300-MUg dosage caused significant arrestment of upwind
      flight. Peak response to synthetics, however, was significantly lower than to
      female glands. Omitting decyl acetate from the blend did not affect the activity,
      while omission of any of the three monounsaturated acetates caused a dramatic
      decrease in response. In the field maximum trap catches were achieved with 1- to
      30-MUg lures. The subtractive assay carried out in the field confirmed the
      neutrality of decyl acetate and the importance of the three monoenes. Adding 1%
      of (Z)-8-dodecenyl acetate (earlier reported as an "inhibitor") to the four
      component mixture decreased the trap catch to about 50%, and increasing the
      amount of (Z)-8-dodecenyl acetate to 27% decreased the activity further to about
      10%. (Z)-8-Dodecenyl acetate also decreased the number of successful flights in
      the flight tunnel. 

PMID- 24310384
TI  - Novel components from secretory hairs of azalea lace bugStephanitis pyrioides
      (Hemiptera: Tingidae).
AB  - The azalea lace bug secretes a clear fluid from secretory setae on the antennae
      and globulated spines on the dorsal and lateral aspects of the abdomen. The
      secretion contains 2-alkyl-5-hydroxychromones, the corresponding chromanones and
      diketones, and straight-chain aldehydes and ketones. 

PMID- 24310385
TI  - Identification of feeding stimulants for boll weevils from cotton buds and
      anthers.
AB  - Column chromatography of the pentane extract of freeze-dried cotton buds or
      anthers yielded a wax-sterol ester fraction that exhibited potent feeding
      stimulant activity for the cotton boll weevil. The waxes of the wax-sterol ester
      mixture were responsible for the feeding activity. Saponification of the wax
      sterol ester fraction yielded about 15% alcohols and 85% sterols. A C18?1
      alcohol, dihydrophytol, phytol, and geranylgeraniol constituted 15, 36, 26, and
      23%, respectively, of the total alcohols, implicating certain of their long-chain
      esters as feeding stimulants. Several esters of dihydrophytol, phytol, and
      geranylgeraniol were identified among the waxes by GC-MS. Certain phytol,
      geranylgeraniol, and oleyl alcohol esters containing C12 to C26 acid moieties
      were synthesized and were found to induce high feeding stimulant activity in the
      cotton boll weevil. 

PMID- 24310386
TI  - Video camera-computer tracking of nematodeCaenorhabditis elegans to record
      behavioral responses.
AB  - A new method is used to analyze responses to changes in the concentration of two
      chemical stimuli. Nematodes are allowed to move around on the surface of a thin
      layer of agar across which a stream of air blows to carry volatile stimuli.
      Darkfield illumination provides high-contrast images of the worms which are
      acquired by a video camera and fed to a microcomputer which is programed to
      simultaneously track and record the movements and changes in direction of as many
      as 25 animals. The results are reported in real time. The worms respond to an
      increase in CO2 concentration by decreasing the number moving and increasing the
      number of changes of direction. Both responses adapt to steady-state levels in
      about half a minute. This suggests that they respond by changing the probability
      of initiating a reversal bout. This observation adds a repellent to the class of
      stimuli thatC. elegans reponds to by klinokinesis. The resonses to changes in
      oxygen concentration are somewhat different. Movements and changes in direction
      both decrease when the oxygen concentration falls and increase when the
      concentration rises. No adaptation is seen within the one-minute time span
      observed. This observation provides further evidence that the response to oxygen
      differs from the response to other chemicals and may be sensed internally. These
      observations demonstrate that computer tracking is a sensitive method of
      analyzing animal behavior. It is further demonstrated that a significant response
      can be detected to a relatively weak stimulus in less than 5 min. 

PMID- 24310387
TI  - Behavior of the western pine beetle during host colonization.
AB  - After living ponderosa pines were baited with either female-infested bolts or
      synthetic pheromones,Dendroctonus brevicomis were caught on sticky screens
      throughout trapping periods of 15-46 days; however, large numbers of beetles were
      trapped during only a small portion (5-10 days) of these trapping periods. The
      most attractive portions of trees attacked contained 3-6 beetles dm(2), in
      galleries ca. 2 cm long. Catch increased following addition of males to female
      infested bolts, supporting the hypothesis that male-produced frontalin is an
      attractive pheromone of the western pine beetle. Catch at bolts removed from
      trees under attack was strongly dependent upon levels of boring activity. We
      found no evidence of interruption of the response to attractants during host
      colonization. 

PMID- 24310388
TI  - (R (*),S (*))-5-hydroxy-4-methyl-3-heptanone male-produced aggregation pheromone
      ofSitophilus oryzae (L.) andS. zeamais motsch.
AB  - A male-produced aggregation pheromone, common to the rice weevil,Sitophilus
      oryzae, and the maize weevil,S. zeamais, was isolated and identified from hexane
      extracts of highly absorbent paper disks exposed individually to young virgin
      male weevils. A combination of preparative column and gas-liquid chromatography
      of disk extracts yielded purified natural pheromone. When analyzed by nuclear
      magnetic resonance spectroscopy and gas chromatography-mass spectrometry, the
      structure of the natural pheromone, "sitophilure," proved to be (R (*),S (*))-5
      hydroxy-4-methyl-3-heptanone, of unknown enantiomeric composition. Synthetic
      racemic pheromone was highly attractive to males and females of both rice and
      maize weevils. In addition, both sexes of the granary weevil,S. granarius (L.)
      were attracted to the racemic preparation. 

PMID- 24310389
TI  - Studies on relationship between activity and electron density on carbonyl oxygen
      in sex pheromone mimics of the American cockroach, part XI.
AB  - From the relationship between structures of the 2alpha-substituents of verbanyl
      analogs and their sex pheromone activities to the American cockroach, electron
      density of the carbonyl oxygen atom in the substituent, as estimated by the
      [(17)O]NMR chemical shift, was estimated to be an important factor which
      influenced the activity, in addition to length of the substituent and the
      position of the carbonyl group. (+)-Verbanyl methylcarbonate (XX), possessing the
      highest electron density on the carbonyl oxygen atom, showed the strongest
      activity among the analogs. 

PMID- 24310390
TI  - Olfactory aposematism : Association of food toxicity with naturally occurring
      odor.
AB  - Visual and acoustic cues may serve as aposematic signals that warn predators of
      poisonous foods. Olfactory aposematism, the use of innocuous odors as warning
      signals for toxic foods, is another possible means of alerting an animal that a
      potential food item is unpalatable. Although it has been suggested that olfactory
      aposematism might be the principle mode of warning utilized by plants in their
      defense against herbivores, experimental evidence is lacking. This study
      demonstrates that the opossum,Didelphis virginiana, can utilize an innocuous
      volatile compound found naturally in a mushroom as a warning signal for a delayed
      illness caused by mushroom toxin. This supports the contention that
      characteristic odors of toxic plants may serve a warning function, protecting
      herbivores from being poisoned and plants from being consumed. 

PMID- 24310391
TI  - Isolation and identification of mosquito repellents inArtemisia vulgaris.
AB  - The mugwortArtemisia vulgaris L. (Compositae: Anthemideae) contains insect
      repellents which can be released from the plant tissues by combustion. Work was
      carried out to isolate and identify the repellent compounds. The dried,
      pulverized whole plants were steam-distilled to give a repellent essential oil
      which was fractionated by column chromatography. Active fractions were analyzed
      by capillary GC and by combined GC-MS. A number of compounds, mainly
      monoterpenoids, were identified. When tested as repellents against the yellow
      fever mosquitoAedes aegypti L. (Diptera: Culicidae), (+/-)-linalool, (+/-)
      camphor, (+)-camphor, (-)-camphor, isoborneol, (-)-borneol, terpinen-4-ol, and
      isobornyl acetate were active at 0.14 mg/cm2 or higher. Nonanone-3, (alpha+beta)
      thujone, and bornyl acetate were active at 0.28 mg/cm(2) or higher. beta-Pinene,
      myrcene, alpha-terpinene, (+)- limonene, and cineole were active at 1.4 mg/cm(2).
      Of the repellent compounds identified, terpinen-4-ol was the most active and was
      as effective as dimethyl phthalate. 

PMID- 24310392
TI  - Disposition and fate of cucurbitacin B in five species of diabroticites.
AB  - Five species of diabroticites with different host-plant preferences produced an
      essentially identical array of metabolites when fed radiolabeled cucurbitacin B
      synthesized in vivo and purified fromCucurbita maxima Duchesne seedlings. All
      species excreted the bulk of the cucurbitacin (67,17-94.59% total dpm),
      permanently sequestered a small proportion of a cucurbitacin conjugate in the
      hemolymph (0.98-2.76%), and apportioned the remainder between the gut, the body,
      and the eggs (when present). Markedly different ratios between the excretory
      metabolites (i.e., polar vs. unmetabolized cuc) suggest thatDibrotica virgifera
      virgifera, a grass specialist, andAcalymma vittatum, a cucurbit specialist, have
      lower rates of metabolic alteration than the polyphagousD. undecimpunctata
      howardi, D. balteata, andD. cristata, which is associated with relict prairies.
      Mean life-spans ofD. balteata and D. v. virgifera and maleA. vittatum decreased
      significantly with continuous feeding onCucurbita fruit containing cucurbitacins
      (vs. fruit devoid of cucs). The longevity of femaleA. vittatum, however, was
      unaffected by the presence of cucurbitacins. 

PMID- 24310393
TI  - Stimulatory effects of tannins and cholic acid on tryptic hydrolysis of proteins:
      Ecological implications.
AB  - The biochemical basis for considering tannins as digestion inhibitors has been
      reexamined. Both stimulatory and inhibitory effects of tannins on tryptic
      hydrolysis are reported. We show how stimulation may result from tannin-induced
      structural changes in the substrate protein, effectively denaturing it. The
      surfactant and bile constituent cholic acid also produced similar stimulatory
      effects. These results have considerable implications for normal digestive
      physiology as well as for the impact of tannins on argicultural and natural
      herbivore populations. 

PMID- 24310394
TI  - High spin-Chern insulators with magnetic order.
AB  - As a topological insulator, the quantum Hall (QH) effect is indexed by the Chern
      and spin-Chern numbers C and Cspin. We have only Cspin = 0 or +/- 1/2 in
      conventional QH systems. We investigate QH effects in generic monolayer honeycomb
      systems. We search for spin-resolved characteristic patterns by exploring
      Hofstadter's butterfly diagrams in the lattice theory and fan diagrams in the low
      energy Dirac theory. It is shown that the spin-Chern number can takes an
      arbitrary high value for certain QH systems. This is a new type of topological
      insulators, which we may call high spin-Chern insulators. Samples may be provided
      by graphene on the SiC substrate with ferromagnetic order, transition-metal
      dichalcogenides with ferromagnetic order, transition-metal oxide with
      antiferromagnetic order and silicene with ferromagnetic order. Actually high spin
      Chern insulators are ubiquitous in any systems with magnetic order. Nevertheless,
      the honeycomb system would provide us with unique materials for practical
      materialization.

PMID- 24310395
TI  - The World Health Assembly resolutions on eHealth: eHealth in support of universal
      health coverage.
AB  - The World Health Assembly (WHA) of the World Health Organization (WHO) and three
      of the six WHO Regional Committees adopted a number of resolutions on eHealth:
      the use of information and communication technology for health. These resolutions
      have given legitimacy to eHealth as an area of work for WHO and its member
      states. The implementation of these resolutions will contribute to the
      achievement of the Millennium Development Goals (MDGs) and the Universal Health
      Coverage. eHealth has been perceived as reducing the cost of healthcare,
      improving quality and equitable access to health services.

PMID- 24310396
TI  - Know thyself.
AB  - This article is part of a For-Discussion-Section of Methods of Information in
      Medicine on "Biomedical Informatics: We Are What We Publish" written by Peter L.
      Elkin, Steven H. Brown, and Graham Wright. It is introduced by this editorial and
      followed by a commentary paper with invited comments. In their paper, P. Elkin et
      al. attempt to define the fields of Medical Informatics and Bioinformatics
      through a bottom-up approach by searching the medical literature. This innovative
      approach provides interesting results that are discussed in the commentary paper.
      In subsequent issues the discussion may continue through letters to the editor.

PMID- 24310397
TI  - Discussion of "Biomedical informatics: we are what we publish".
AB  - This article is part of a For-Discussion-Section of Methods of Information in
      Medicine about the paper "Biomedical Informatics: We Are What We Publish",
      written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced
      by an editorial. This article contains the combined commentaries invited to
      independently comment on the Elkin et al. paper. In subsequent issues the
      discussion can continue through letters to the editor. 

PMID- 24310398
TI  - A preclinical assay for chemosensitivity in multiple myeloma.
AB  - Accurate preclinical predictions of the clinical efficacy of experimental cancer
      drugs are highly desired but often haphazard. Such predictions might be improved
      by incorporating elements of the tumor microenvironment in preclinical models by
      providing a more physiological setting. In generating improved xenograft models,
      it is generally accepted that the use of primary tumors from patients are
      preferable to clonal tumor cell lines. Here we describe an interdisciplinary
      platform to study drug response in multiple myeloma, an incurable cancer of the
      bone marrow. This platform uses microfluidic technology to minimize the number of
      cells per experiment, while incorporating three-dimensional extracellular matrix
      and mesenchymal cells derived from the tumor microenvironment. We used sequential
      imaging and a novel digital imaging analysis algorithm to quantify changes in
      cell viability. Computational models were used to convert experimental data into
      dose-exposure-response "surfaces," which offered predictive utility. Using this
      platform, we predicted chemosensitivity to bortezomib and melphalan, two clinical
      multiple myeloma treatments, in three multiple myeloma cell lines and seven
      patient-derived primary multiple myeloma cell populations. We also demonstrated
      how this system could be used to investigate environment-mediated drug resistance
      and drug combinations that target it. This interdisciplinary preclinical assay is
      capable of generating quantitative data that can be used in computational models
      of clinical response, demonstrating its utility as a tool to contribute to
      personalized oncology.

PMID- 24310400
TI  - Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma is a treatment refractory malignancy with a high
      mortality and an increasing incidence worldwide. Recent studies have observed
      that activation of Notch and AKT signaling within mature hepatocytes is able to
      induce the formation of tumors displaying biliary lineage markers, thereby
      raising the suggestion that it is hepatocytes, rather than cholangiocytes or
      hepatic progenitor cells that represent the cell of origin of this tumor. Here,
      we use a cholangiocyte-lineage tracing system to target p53 loss to biliary
      epithelia and observe the appearance of labeled biliary lineage tumors in
      response to chronic injury. Consequent to this, upregulation of native functional
      Notch signaling is observed to occur spontaneously within cholangiocytes and
      hepatocytes in this model as well as in human intrahepatic cholangiocarcinoma.
      These data prove that in the context of chronic inflammation and p53 loss,
      frequent occurrences in human disease, biliary epithelia are a target of
      transformation and an origin of intrahepatic cholangiocarcinoma.

PMID- 24310399
TI  - Extracellular vesicles modulate the glioblastoma microenvironment via a tumor
      suppression signaling network directed by miR-1.
AB  - Extracellular vesicles have emerged as important mediators of intercellular
      communication in cancer, including by conveying tumor-promoting microRNAs between
      cells, but their regulation is poorly understood. In this study, we report the
      findings of a comparative microRNA profiling and functional analysis in human
      glioblastoma that identifies miR-1 as an orchestrator of extracellular vesicle
      function and glioblastoma growth and invasion. Ectopic expression of miR-1 in
      glioblastoma cells blocked in vivo growth, neovascularization, and invasiveness.
      These effects were associated with a role for miR-1 in intercellular
      communication in the microenvironment mediated by extracellular vesicles released
      by cancer stem-like glioblastoma cells. An extracellular vesicle-dependent
      phenotype defined by glioblastoma invasion, neurosphere growth, and endothelial
      tube formation was mitigated by loading miR-1 into glioblastoma-derived
      extracellular vesicles. Protein cargo in extracellular vesicles was characterized
      to learn how miR-1 directed extracellular vesicle function. The mRNA encoding
      Annexin A2 (ANXA2), one of the most abundant proteins in glioblastoma-derived
      extracellular vesicles, was found to be a direct target of miR-1 control. In
      addition, extracellular vesicle-derived miR-1 along with other ANXA2
      extracellular vesicle networking partners targeted multiple pro-oncogenic signals
      in cells within the glioblastoma microenvironment. Together, our results showed
      how extracellular vesicle signaling promotes the malignant character of
      glioblastoma and how ectopic expression of miR-1 can mitigate this character,
      with possible implications for how to develop a unique miRNA-based therapy for
      glioblastoma management.

PMID- 24310402
TI  - Interactions of S alleles in sporophytically controlled self incompatibility of
      Brassica.
AB  - The expressed activity in pollen and stigma was determined for both S alleles of
      sixteen S-aliele heterozygous genotypes and for one of the two S alleles of two
      additional heterozygotes. Activities were measured using pollen tube penetration
      and seed set data from reciprocal crosses between each S-allele heterozygote and
      its two corresponding S-allele homozygotes.In pollen the S-allele activities
      ranged from zero to 100% inhibition of pollen tube penetration and seed set, and
      in the stigma they ranged from 8 to 100% inhibition. Of the sixty-eight S-allele
      activities measured, thirty-three (48%) were 90 to 100% inhibition, nine (13%)
      were 80 to 89% inhibition and one to five were within each ten-unit range below
      80% inhibition.In an S-allele heterozygote, each subset of two S alleles had an
      activity for each allele in both pollen and stigma which was highly repeatable
      among duplicate pollinations within and among successive years. Each subset of
      two S alleles had a specific S-allele interaction in the pollen, and the same or
      another specific interaction in the stigma. In pairings with six other S alleles,
      allele S 2 had four calculated levels of activity in pollen that ranged from 88
      to 94%, and five levels in the stigmas between 15 and 94%. When paired in a
      heterozygote, alleles S 3 and S 5 had activities ranging between 42 and 59%,
      representing mutual weakening of S-allele activity. Also, heterozygote S 15 S 3
      had pollen activities, respectively, of 25 and 6%, i.e. mutual weakening in the
      pollen.These results indicate that in heterozygous combination with a series of
      other S alleles, each S-allele may have activity in pollen and also in stigma
      that potentially is between zero and 100% inhibition. They further indicate that
      the defined sexual-organ X S-allele-interaction Types I, II, III and IV are
      extremes; all intermediate variations including complete weakening of both
      alleles are possible. Recessiveness is weakening of the activity of but one of
      the two S alleles. The pollen tube penetrations into the style and seed set were
      highly correlated. 

PMID- 24310401
TI  - Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice.
AB  - OBJECTIVE: Besides their role in lipid absorption, bile acids (BAs) can act as
      signalling molecules. Cholic acid was shown to counteract obesity and associated
      metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy
      expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and
      activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this
      study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on
      dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue
      (brite cells in WAT), were characterized in dietary-obese mice. RESEARCH DESIGN:
      To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J
      mice were fed cHF (35% lipid wt wt(-1), mainly corn oil) for 4 months. Mice were
      then fed either (i) for 8 weeks with cHF or with cHF with two different doses
      (0.5%, 1%; wt wt(-1)) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or
      with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice
      fed ad libitum; mice on standard chow diet were also used (3-week reversion).
      RESULTS: In the 8-week reversion, the CDCA intervention resulted in a dose
      dependent reduction of obesity, dyslipidaemia and glucose intolerance, which
      could be largely explained by a transient decrease in food intake. The 3-week
      reversion revealed mild CDCA-dependent and food intake-independent induction of
      UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in
      subcutaneous WAT and a shift from carbohydrate to lipid oxidation. CONCLUSIONS:
      CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction
      in food intake, an effect probably occuring but neglected in previous studies
      using cholic acid. Nevertheless, CDCA-dependent and food intake-independent
      induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in
      adiposity and to the stabilization of the lean phenotype.

PMID- 24310403
TI  - Are "multiple cross-multiple pollen hybrids' an answer for productive populations
      in Brassica campestris var. 'brown sarson'? : I. Methods for studying
      'mucromphs'.
AB  - A set of complex crosses with multiple crosses as female parents were made using
      multiple pollen in turnip rape (Brassica campestris L.). These multiple cross -
      multiple pollen hybrids (mucromphs) were evaluated for a large number of
      quantitative characters including yield. New methods were proposed to study such
      genetic material in depth so as to formulate suitable strategies to breed for
      attractive seed yield. 

PMID- 24310404
TI  - Callus formation from cell culture protoplasts of corn (Zea mays L.).
AB  - Routine procedures for the isolation of large numbers of protoplasts from an
      established cell culture of Zea mays and for the induction of sustained divisions
      leading to secondary cell cultures have been developed. The critical factors seem
      to be associated with neither specific enzymatic conditions for the isolation nor
      specific culture conditions for the protoplasts but with the 'quality' of the
      culture used for protoplast isolation. 

PMID- 24310405
TI  - Mentor pollen effects on gametophytic incompatibility in Nicotiana, Oenothera and
      Lycopersicum.
AB  - Attempts were made, through mentor pollen techniques, to overcome self
      incompatibility in species belonging to the genera Nicotiana and Oenothera and in
      a hybrid of Lycopersicum, which are characterized by a gametophytic system of
      incompatibility. While radiation-killed incompatible pollen did not generate
      mentor effects in any of the material tested, radiation-killed compatible pollen
      was found to promote a high level of illegitimate fertilizations by incompatible
      pollen in N. alata. No evidence was obtained that radiation-killed compatible
      pollen could induce mentor effects in strictly self-incompatible clones of O.
      organensis and of the interspecific hybrid L. esculentum x L. peruvianum. 

PMID- 24310406
TI  - Characteristics of nuclear DNA in the genus Oryza.
AB  - DNAs have been isolated from various Oryza species and studied using physical
      techniques. The percent of guanine plus cytosine has been determined by thermal
      denaturation. While the base composition varied between the species, no
      heterogeneity in the base pair distribution was observed. Renaturation kinetics
      data of DNAs from different species show that the proportion of repeated DNA
      sequences vary considerably depending on the DNA content per cell, whereas the
      nonrepetitive DNA component remains relatively constant. These results suggest
      that in addition to a small range of DNA variation between the species, changes
      in the base composition and proportion of repeated sequences have accompanied
      divergence of the species within the genus. 

PMID- 24310407
TI  - Model for genetic control of Heliothis virescens.
AB  - A model was developed which corrects and extends an earlier one proposed for the
      control of the tobacco budworm, Heliothis virescens (F.), through hybrid male
      sterility. Population suppression is effected through the release into natural
      populations of the backcross progeny of a hybrid between H. virescens and a
      related species. Thereafter, the system perpetuates itself in nature through
      continual backcrossing of the fertile backcross females to native H. virescens
      males. When the proportion of backcross hybrid females in the total population is
      large enough to draw off the insemination potential of the native males, the
      native females fail to replace themselves. The present model demonstrated that
      the ratio of released backcross hybrids to natural H. virescens remains constant
      in a closed population. Furthermore it was shown that the release ratio necessary
      to achieve extinction of a closed population is related to the number of females
      that a male can inseminate and to the population growth rate. Release ratios
      required to slow natural population growth and to lessen the impact damage of
      releases on crop plants were also examined. Effects of selection against the
      backcross females on the predictions of the model were explored. 

PMID- 24310408
TI  - The alpha-glycerophosphate dehydrogenase (alpha-gpdh) polymorphism in Drosophila
      melanogaster: adult survival under temperature stress.
AB  - As a test of the hypothesis that adult temperature stress is an important
      component of natural selection maintaining the alpha-gpdh polymorphism, we have
      looked for differential survival among genotypes subjected to (i) heat shock and
      (ii) cold shock. Factorial ANOVAR, taking account of genotype, sex and
      temperature-stress indicated that genotype did not contribute to the variance of
      survival proportion per vial. We have not therefore found evidence to support our
      hypothesis. Incidental to the above was a significant sex-temperature
      interaction. Thus, adult females showed higher survival than males under heat
      stress, while under cold stress, there was no indication of a survival difference
      between the sexes. 

PMID- 24310409
TI  - Duplicated origin of a radiculomedullary artery supplying a perimedullary
      arteriovenous fistula: angiographic observation and developmental considerations.
AB  - The angiographic observation of a radiculomedullary artery variation found in a
      patient with a spinal cord vascular malformation is presented. A posterior
      radiculomedullary artery arising from the left L2 intersegmental artery had a
      duplicated origin. Two radicular trunks were seen aiming towards the neural
      foramen: a dominant anterior one providing a retrocorporeal artery and the
      anterior limb of the radicular artery, and a smaller posterior one branching off
      a prelaminar artery and the posterior limb of the radicular artery. The two limbs
      then joined to continue as a single posterior radiculomedullary artery, which
      participated in the vascularization of the vascular malformation. The clinical
      and developmental aspects of this exceptional variant are discussed. 

PMID- 24310410
TI  - Variations of the hepatobiliary vasculature including coexistence of accessory
      right hepatic artery with unusually arising double cystic arteries: case report
      and literature review.
AB  - Familiarity with the different anatomical variations of the arterial supply of
      the gallbladder and liver is of great importance in all hepatobiliary surgical
      procedures. A complex anomaly of the hepatobiliary arterial system, which has
      never been reported before, was found during anatomical dissection of a 73-year
      old male Caucasian cadaver. The accessory right hepatic artery (aRHA) took its
      origin from the gastroduodenal artery. Two cystic arteries were present, the
      first arising from the gastroduodenal artery (more distal than the aRHA) and the
      second directly from the aRHA. Potential clinical implications of this anomaly
      and embryology are discussed. Knowledge of the different anatomical variations of
      the arterial supply of the gallbladder and liver is of great importance in
      hepatobiliary surgical procedures. 

PMID- 24310411
TI  - Response to: Media effect-letter to the editor about the manuscript titled
      Increasing fear of adverse effects drops intention to vaccinate after the
      introduction of prophylactic HPV vaccine.

PMID- 24310412
TI  - An experimental study of the effect of structured videotape feedback on
      adolescent group psychotherapy process.
AB  - Group psychotherapy with disturbed undersocialized adolescents requires
      modification of traditional group psychotherapy methods. The effectiveness of a
      structured, brief video-tape feedback and discussion on group psychotherapy
      process with this population was studied by an analysis of detailed ratings of
      each "statement", or process unit; in randomly selected videotapes from a control
      and experimental group during a nine-month period. Significant differences in
      level of intimacy of verbal content and in frequency of feedback about behavior
      in content indicate that this technique is effective in facilitating group
      psychotherapy goals. 

PMID- 24310413
TI  - Young adults' moral reasoning about prohibitive and prosocial dilemmas.
AB  - One hundred and five high school and college students were given tasks of social
      sensitivity, perspective taking, prosocial moral reasoning, and prohibitive moral
      reasoning. Social sensitivity and perspective taking were positively related to
      both types of moral reasoning, but only for females. For both males and females,
      level of principled moral reasoning was greater for the prosocial dilemmas than
      for the prohibitive dilemmas. Findings are generally viewed as being supportive
      of Piaget's and Kohlberg's conceptualizations of the nature of moral judgment.
      Differences between the two types of unrelated moral reasoning are discussed in
      terms of the relation between an individually constructed set of ethics and a
      more general social code of ethics. 

PMID- 24310414
TI  - Perceived parental authority: Reasonable and unreasonable.
AB  - A questionnaire study of 844 teenagers from four midwestern high schools focused
      on phenomena associated with their perceptions of which parent was "the real
      boss" and of how reasonable this "boss" was in dealing with the adolescent.
      Father was perceived to be the family authority about three times more often than
      was mother, although sons tended to see father as boss more often than did
      daughters, who tended to see mother as boss more often than did sons. Paternal
      and maternal authorities did not differ in perceived reasonableness. When either
      mother or father was perceived as a reasonable authority, the teenagers saw
      mother as highly involved, objective, and as enjoying life. Perception of high
      reasonableness in paternal authority was associated with the perception of father
      as involved, objective, enjoying life, and as not rigorous in his expectations
      for the child's compliance and achievement. 

PMID- 24310415
TI  - A comparative analysis of personality organization in juvenile anorexia nervosa.
AB  - To identify distinguishing features of personality associated with anorexia
      nervosa in adolescence, univariate and multiple group discriminant function
      analyses were used to compare the Cattell High School Personality Questionnaire
      responses of 50 anorectics and matched groups of depressed and antisocial
      adolescent females. Results indicated the presence of two major sources of
      discriminating variance. Relative to both control groups, anorectics were
      characterized by significantly greater conformity, neurotic anxieties, control of
      emotionality, and stimulus avoidance. These findings suggest that at the level of
      personality functioning, the anorectic has failed to acquire the sense of
      individuation, mastery, and general plasticity of psychological functioning
      necessary to cope effectively with critical developmental tasks and progress
      toward identity formation. Results are discussed in terms of the extant
      literature on anorexia nervosa and future research needs. 

PMID- 24310416
TI  - Ego identity status, ego development, and locus of control in college women.
AB  - This study examined the relationship of identity status to ego development and
      locus of control in 75 college women. The identity statuses did not differ
      significantly in self-reported locus of control, but did differ on the "depth"
      measure of ego development. Consistent with identity theory and with previous
      research with males, identity achievers and moratorium (incrisis) women were more
      advanced in their ego development than fore-closure and diffusion women. 

PMID- 24310417
TI  - Personal problems of adolescents and their relationship to peer acceptance and
      sex-role identity.
AB  - The Mooney Problem Checklist (MPCL), Bem Sex Role Inventory (BSRI) and a series
      of sociometric rating scales were administered to four groups of adolescents (40
      males and 48 females from grade 8-average age = 13.5 years; 39 males and 37
      females from grade 12-average age = 17.5 years). The total number of problems
      reported and the number in many of the 11 areas of the MPCL were fewer in the
      older group of males than the other three groups. As the number of problems was
      expected to decrease with age, it was proposed that females' problem level was
      maintained at a high level by pressures to conform to a feminine sex-role
      identity. This speculation was based on the findings that females became more
      stereotyped (more feminine, less masculine) with age and that femininity was
      significantly related to the number of problems for females. Although masculinity
      and peer group acceptance were expected to relate negatively to the number of
      problems, none of the groups supported the prediction for masculinity, and only
      the younger males confirmed the hypothesis for peer acceptance. 

PMID- 24310418
TI  - Axillary reverse mapping using fluorescence imaging is useful for identifying the
      risk group of postoperative lymphedema in breast cancer patients undergoing
      sentinel node biopsies.
AB  - BACKGROUND: Axillary reverse mapping (ARM) is a novel technique for preserving
      the upper extremity lymphatic pathways during axillary lymph node surgery.
      However, there is no evidence of the usefulness of ARM for patients undergoing
      sentinel lymph node biopsy (SNB). METHODS: Between August 2009 and July 2012, 372
      patients who underwent the SNB procedure for breast cancer were enrolled in this
      study. Using the indocyanine green fluorescence technique and indigocarmine blue
      dye method, we studied the relationship between the upper extremity lymphatic
      flow and breast sentinel node (SN). Our aim of this study was the probability of
      postoperative lymphedema with respect to whether the upper extremity lymphatics
      corresponded to the breast SN. RESULTS: Among the 327 patients who underwent the
      SNB procedure, the upper extremity lymphatics drainage into the breast SN in 76
      (23.2%; corresponding group), and only 5 patients in this group developed
      lymphedema. In contrast, none of the patients in the noncorresponding group
      developed lymphedema. CONCLUSIONS: ARM during SN biopsy can identify the group of
      patients who are at high risk for developing lymphedema. More risk-focused
      guidance should be used for these patients.

PMID- 24310420
TI  - Performance of two MALDI-TOF MS systems for the identification of yeasts isolated
      from bloodstream infections and cerebrospinal fluids using a time-saving direct
      transfer protocol.
AB  - The rapid and correct identification of pathogens is of paramount importance for
      the treatment of patients with invasive infections. Matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) can speed
      up the identification of bacteria and fungi and has quickly been embraced by
      medical microbiology laboratories worldwide. Different MALDI-TOF systems have
      been compared in studies focussing on identification rates of different
      pathogens. Another aspect that has not been systematically assessed is the
      performance in daily routine and handling, which is important especially for
      microbiology routine laboratories. We compared two widespread commercial systems,
      Microflex LT Biotyper (Bruker) and VitekMS (bioMerieux), for the identification
      of 210 relevant clinical yeasts under routine conditions, using a time-saving
      direct transfer protocol. We assessed the need for an additional extraction step,
      the threshold for species identification and the duration of measurements with
      the two systems. The tested yeasts included 34 Candida albicans isolates, 144 non
      albicans Candida spp. and 32 yeasts of different genera. The results of the two
      MS systems were compared with that of biochemical identification and, in case of
      discrepancies, DNA sequencing of the internal transcribed spacer or the large
      subunit of ribosomal DNA. Both systems correctly identified 96.2 % of isolates
      [202/210, non-significant (n.s.)]. Misidentifications were observed for VitekMS
      only (n = 5, no major errors, n.s.). VitekMS was the slower system (19.8 vs. 8.0
      min for 10 samples, p = 0.002) but had the advantage of a more effective direct
      transfer protocol with less need for an additional extraction step. 

PMID- 24310419
TI  - Comparative microbiological features of Bartonella henselae infection in a dog
      with fever of unknown origin and granulomatous lymphadenitis.
AB  - We report the first documented case of Bartonella henselae infection in a dog
      from France and the first isolation of B. henselae from a dog with fever of
      unknown origin. This observation contributes to the "One Health" concept focusing
      on zoonotic pathogens emerging from companion animals. A 1-year-old female German
      shepherd dog was referred for evaluation of fever of unknown origin of 1 month
      duration. Diagnostic investigations confirmed diffuse pyogranulomatous
      lymphadenitis. The dog became afebrile, and lymph node size normalized in
      response to a 6-week course of doxycycline. Retrospectively, Bartonella DNA was
      amplified from an EDTA-anticoagulated blood sample obtained before antimicrobial
      therapy, with the gtlA fragment sharing 99 % identity with the 350-bp gtlA
      fragment of the B. henselae Houston-1 strain. The same strain was isolated in the
      blood of three healthy cats from the household. Two months after discontinuation
      of doxycycline, the dog experienced a febrile relapse. Bartonella DNA was again
      amplified from blood prior to and immediately after administration of a 6-week
      course azithromycin therapy. However, without administration of additional
      medications, PCR was negative 9 months after azithromycin therapy and the dog
      remains clinically healthy 12 months following the second course of antibiotics.
      The medical management of this case raises several clinically relevant
      comparative infectious disease issues, including the extent to which Bartonella
      spp. contribute to fever of unknown origin and pyogranulomatous inflammatory
      diseases in dogs and humans, and the potential of doxycycline and azithromycin
      treatment failures. The possibility that dogs could constitute an underestimated
      reservoir for B. henselae transmission to people is also discussed. 

PMID- 24310422
TI  - One-pot synthesis of D-glucosamine and chitobiosyl building blocks catalyzed by
      triflic acid on molecular sieves.
AB  - Combining triflic acid-catalyzed acetalation, benzylation, reductive ring opening
      of benzylidene acetal and glycosylation in one-pot transformations leads to a
      wide range of d-glucosamine building blocks for assembling oligomers. 

PMID- 24310423
TI  - Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats.
AB  - We have reported that PEGylated liposomes lose their long-circulating properties
      when they are administered repeatedly at certain intervals to the same animal.
      This unexpected phenomenon is referred to as the accelerated blood clearance
      (ABC) phenomenon. We recently showed that the ABC phenomenon is triggered via the
      abundant secretion of anti-PEG IgM in response to the first dose of PEGylated
      liposomes. However, the details of the underlying mechanism for the induction of
      anti-PEG IgM production are yet to be elucidated. The present study demonstrated
      that the spleen is a major organ involved in the secretion of anti-PEG IgM in
      mice and rats. Anti-PEG IgM production was detected in nude, T-cell deficient
      mice, but not in SCID mice with B- and T-cell deficiencies. These observations
      indicate that splenic B-cells secret anti-PEG IgM without help from T-cells.
      Sequential injections of PEGylated liposomes into the same mice did not promote
      isotype switching from IgM to IgG. Accordingly, PEGylated liposomes may function
      as a type-2, T-cell-independent antigen (TI-2 antigen) during anti-PEG IgM
      production. Although the underlying mechanism that causes an anti-PEG IgM
      response against PEGylated liposomes is not yet clear, our findings give
      implications in revealing the anti-PEG IgM response against PEGylated liposome. 

PMID- 24310424
TI  - The pharmacokinetics and pharmacodynamics of iron preparations.
AB  - Standard approaches are not appropriate when assessing pharmacokinetics of iron
      supplements due to the ubiquity of endogenous iron, its compartmentalized sites
      of action, and the complexity of the iron metabolism. The primary site of action
      of iron is the erythrocyte, and, in contrast to conventional drugs, no drug
      receptor interaction takes place. Notably, the process of erythropoiesis, i.e.,
      formation of new erythrocytes, takes 3-4 weeks. Accordingly, serum iron
      concentration and area under the curve (AUC) are clinically irrelevant for
      assessing iron utilization. Iron can be administered intravenously in the form of
      polynuclear iron(III)-hydroxide complexes with carbohydrate ligands or orally as
      iron(II) (ferrous) salts or iron(III) (ferric) complexes. Several approaches have
      been employed to study the pharmacodynamics of iron after oral administration.
      Quantification of iron uptake from radiolabeled preparations by the whole body or
      the erythrocytes is optimal, but alternatively total iron transfer can be
      calculated based on known elimination rates and the intrinsic reactivity of
      individual preparations. Degradation kinetics, and thus the safety, of parenteral
      iron preparations are directly related to the molecular weight and the stability
      of the complex. High oral iron doses or rapid release of iron from intravenous
      iron preparations can saturate the iron transport system, resulting in oxidative
      stress with adverse clinical and subclinical consequences. Appropriate
      pharmacokinetics and pharmacodynamics analyses will greatly assist our
      understanding of the likely contribution of novel preparations to the management
      of anemia. 

PMID- 24310425
TI  - Factors and Mechanisms for Pharmacokinetic Differences between Pediatric
      Population and Adults.
AB  - Many physiologic differences between children and adults may result in age
      related changes in pharmacokinetics and pharmacodynamics. Factors such as gastric
      pH and emptying time, intestinal transit time, immaturity of secretion and
      activity of bile and pancreatic fluid among other factors determine the oral
      bioavailability of pediatric and adult populations. Anatomical, physiological and
      biochemical characteristics in children also affect the bioavailability of other
      routes of administration. Key factors explaining differences in drug distribution
      between the pediatric population and adults are membrane permeability, plasma
      protein binding and total body water. As far as drug metabolism is concerned,
      important differences have been found in the pediatric population compared with
      adults both for phase I and phase II metabolic enzymes. Immaturity of glomerular
      filtration, renal tubular secretion and tubular reabsorption at birth and their
      maturation determine the different excretion of drugs in the pediatric population
      compared to adults. 

PMID- 24310426
TI  - Development of a New Type of Prolonged Release Hydrocodone Formulation Based on
      Egalet(r) ADPREM Technology Using In Vivo-In Vitro Correlation.
AB  - A novel abuse deterrent, prolonged release tablet formulation of Hydrocodone for
      once-daily dosing has been developed, based on the novel proprietary Egalet(r)
      ADPREM technology. The tablet is an injection molded polymer system consisting of
      an erodible matrix in which the Active Pharmaceutical Ingredient (API), such as
      Hydrocodone, is dispersed. The matrix is partly covered with a water-impermeable,
      non-erodible shell which leaves both ends of the cylindrical tablet exposed to
      erosion by the gastrointestinal (GI) fluid. In vivo-in vitro correlation (IVIVC)
      was initiated and validated with three formulations. A good internal
      predictability was observed for the three formulations. How the changing
      conditions in the GI tract influenced in vivo performance of an erosion based
      product was discussed. The validated IVIVC could be used to optimize the tablet
      formulation and to obtain a desired profile. In addition, this technique could
      help to establish the dissolution limits in which a certainty of bioequivalence
      is calculated. Based on this validated level A IVIVC, dissolution can be used as
      surrogate of bioequivalence for development, but also scale up post approval
      changes. 

PMID- 24310427
TI  - First Quantitative Imaging of Organic Fluorine within Angiogenic Tissues by
      Particle Induced Gamma-Ray Emission (PIGE) Analysis: First PIGE Organic Fluorine
      Imaging.
AB  - PET (Positron Emission Tomography) allows imaging of the in vivo distribution of
      biochemical compounds labeled with a radioactive tracer, mainly 18F-FDG (2-deoxy
      2-[18F] fluoro-D-glucose). 18F only allows a relatively poor spatial resolution
      (2-3 mm) which does not allow imaging of small tumors or specific small size
      tissues, e.g. vasculature. Unfortunately, angiogenesis is a key process in
      various physiologic and pathologic processes and is, for instance, involved in
      modern anticancer approaches. Thus ability to visualize angiogenesis could allow
      early diagnosis and help to monitor the response of cancer to specific
      chemotherapies. Therefore, indirect analytical techniques are required to assess
      the localization of fluorinated compounds at a micrometric scale. Multimodality
      imaging approaches could provide accurate information on the metabolic activity
      of the target tissue. In this article, PIGE method (Particle Induced Gamma-ray
      Emission) was used to determine fluorinated tracers by the nuclear reaction of
      19F(p,p'gamma)19F in tissues. The feasibility of this approach was assessed on
      polyfluorinated model glucose compounds and novel peptide-based tracer designed
      for angiogenesis imaging. Our results describe the first mapping of the
      biodistribution of fluorinated compounds in both vascularized normal tissue and
      tumor tissue. 

PMID- 24310429
TI  - The new patent law may accelerate innovation in ophthalmology.

PMID- 24310428
TI  - Cell migration and invasion assays as tools for drug discovery.
AB  - Cell migration and invasion are processes that offer rich targets for
      intervention in key physiologic and pathologic phenomena such as wound healing
      and cancer metastasis. With the advent of high-throughput and high content
      imaging systems, there has been a movement towards the use of physiologically
      relevant cell-based assays earlier in the testing paradigm. This allows more
      effective identification of lead compounds and recognition of undesirable effects
      sooner in the drug discovery screening process. This article will review the
      effective use of several principle formats for studying cell motility: scratch
      assays, transmembrane assays, microfluidic devices and cell exclusion zone
      assays. 

PMID- 24310430
TI  - Localization and nucleotide sequence of the gene for the membrane polypeptide D2
      from pea chloroplast DNA.
AB  - The gene for the membrane polypeptide D2 has been mapped on the pea (Pisum
      sativum) chloroplast genome. The nucleotide sequence of the gene and its flanking
      regions is presented. The only large open reading frame in the sequence codes for
      a protein of MW 39.5 kD. A potential ribosome binding site is located 6
      nucleotides upstream from the initiation codon and there are two sets of putative
      promotor sequences in the 5' flanking region. The polypeptide has a high content
      of hydrophobic amino acids, predominatly grouped in clusters of 20 or more
      residues. The 3' end of the D2 gene is overlapped by 50 nucleotides of a second
      open reading frame (UORF I) which is at least 369 nucleotides long. Based on
      current data we suggest the D2 polypeptide to be a constituent of photosystem II
      (PSII). 

PMID- 24310431
TI  - A review of the structure and organization of the mitochondrial genome of higher
      plants.
AB  - The structure, organisation and functions of the mitochondrial genome of most
      groups of eukaryotic organisms are known to varying degrees with the notable
      exception of higher plants. With the recent completion of physical mapping
      studies on the Brassica campestris (Chinese cabbage, turnip) and Zea mays (maize)
      mitochondrial genomes, many of the apparent problems of plant mitochondrial
      genome structure can now be answered. In this manuscript I review the literature
      relating to the physical observations on plant mitochondrial DNA (mtDNA) and
      assess the data in relation to our current understanding of mitochondrial genome
      structure. 

PMID- 24310432
TI  - DNA primase activity from wheat embryos.
AB  - DNA primase is a recently discovered enzyme capable of synthesizing short primers
      involved in the initiation of DNA replication.Partially purified preparations
      from 4 h germinated wheat embryos or commercial wheat germ are able to catalyze
      the ribonucleoside triphosphate dependent synthesis of DNA with poly dT and M13
      single stranded DNA as templates. DNA synthesis is completely dependent on the
      presence of template and primase. Primase activity from wheat embryos has a
      molecular weight of about 110000 and a sedimentation coefficient of 5S. The
      enzyme activity is not inhibited by alpha-amanitin (1 mg/ml) or aphidicolin when
      the latter is assayed with endogeneous plant DNA polymerase activity. Alkaline
      hydrolysis of the product synthesized in the presence of [alpha-(32)P]dATP and
      poly dT generates [(32)P]-labeled 3'(2')AMP showing that a ribo-deoxynucleotide
      linkage is formed. The size of the oligoribonucleotide primer varies from 2 to 15
      residues. Most of the wheat DNA polymerase activity can be eliminated by
      phosphocellulose chromatography, since the bulk of plant DNA primase is not
      retained by this resin. Nevertheless, a small but significant amoung of DNA
      polymerase activity is found associated with DNA primase. By using different
      inhibitors of DNA polymerase different templates, we have found good indications
      that DNA polymerase A (gamma-like) is associated with the DNA primase. Moreover,
      when the previously purified DNA polymerases from wheat embryos (2) were assayed
      in the presence of primase activity, only DNA polymerase A was able to stimulate
      DNA synthesis. 

PMID- 24310434
TI  - Subcellular localization of glutelin-2 in maize (Zea mays L.) endosperm.
AB  - Accumulation of the 28 KD protein of the glutelin-(G2) fraction was followed in
      developing maize endosperm, using sodium dodecylsulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) and peak integration of scanned gels. 28 KD glutelin-2
      could already be observed from 15 days after pollination and its accumulates
      reached a plateau during the second half of the development period. The process
      of biosynthesis of 28 KD glutelin-2 and zeins occurs in a parallel way.
      Subcellular fractions obtained from linear sucrose gradient centrifugation of
      developing maize endosperms were analyzed by SDS-PAGE and immunoblotting using a
      serum reacting against glutelin-2 and 14 KD Z2. Glutelin-2 was found to be
      present in the protein bodies when subcellular fractionation was carried out
      without dithiothreitol (DTT). The presence of a reducing agent causes the elution
      of glutelin-2 from protein bodies. Immunocytochemical labelling using the protein
      A-colloidal gold technique in protein bodies incubated with anti-G2 IgG revealed
      that G2 is located mainly in the periphery of protein bodies. These results are
      interpreted as indicating a structural role for glutelins in protein bodies. 

PMID- 24310433
TI  - Enzymatic properties of plant RNA polymerases : An approach to the study of
      transcription in plants.
AB  - Results obtained in the past few years in the study of the reaction mechanism of
      plant RNA polymerases are reviewed and discussed. They suggest that valuable
      information can be obtained using a highly simplified transcription system
      composed of purified plant enzymes and cloned genes. This type of approach may
      provide a starting point for the development of an in vitro transcription system.
      The detailed study of the fundamental enzymatic properties of the plant RNA
      polymerases allows a comparison with the well documented corresponding bacterial
      enzyme. 

PMID- 24310435
TI  - Cloning of Petunia hybrida chloroplast DNA sequences capable of autonomous
      replication in yeast.
AB  - Sequences from Petunia hybrida chloroplast DNA which have the property to promote
      autonomous replication in Saccharomyces cerevisiae were cloned in vector YIp5.
      Seven cloned chloroplast DNA fragments are localized at one of two different
      sites on the chloroplast genome. One site, arsA was mapped on a 1.8 Kb fragment
      at position 27.0-28.8 Kb on the P. hybrida chloroplast genome. The plasmids
      containing this arsA are stable both in yeast and E. coli. The other site, arsB,
      was shown to be very unstable and is located either in the small single copy
      region close to the inverted repeat or just in the inverted repeat. The
      functioning of these sequences as a possible origin of replication in vivo is
      discussed. 

PMID- 24310436
TI  - Hybridization study of developmental plastid gene expression in mustard (Sinapsis
      alba L.) with cloned probes for most plastid DNA regions.
AB  - An approach to assess the extent of developmental gene expression of various
      regions of plastid (pt)DNA in mustard (Sinapis alba L.) is described. It involves
      cloning of most ptDNA regions. The cloned regions then serve as hybridization
      probes to detect and assess the abundance of complementary RNA sequences
      represented in total plastid RNA. By comparison of the hybridization pattern
      observed with plastid RNA from either dark-grown or light-grown plants it was
      found that many ptDNA regions are constitutively expressed, while several
      'inducible' regions account for much higher transcript levels in the chloroplast
      than in the etioplast stage. The reverse situation, i.e. 'repressed' regions
      which would account for higher transcript levels in the etioplast, was not
      observed. The hybridization results obtained with RNA from 'intermediatetype'
      plastids suggest that transient gene expression is a common feature during light
      induced chloroplast development. The time-course of gene expression differs for
      various ptDNA regions. 

PMID- 24310437
TI  - Isolation, sequence and expression of two members of the 32 kd thylakoid membrane
      protein gene family from the cyanobacterium Anabaena 7120.
AB  - The cyanobacterium Anabaena contains at least three copies of DNA sequences
      related to the unique gene encoding the 32 kd thylakoid membrane protein in
      spinach chloroplast DNA, based on hybridization with the cloned spinach probe.
      Two of the identified Anabaena DNA fragments were isolated from a recombinant
      lambda library and the complete nucleotide sequences of the coding regions were
      determined. Both fragments contain open reading frames coding for proteins of MW
      39 950. The predicted amino acid sequences are 94% identical; 87% of the
      positions are identical to those of the corresponding spinach protein. The
      nucleotide sequences of the 5' and 3' flanking regions of the two Anabaena genes
      differ considerably. Based on S1 nuclease protection, primer extension, and
      Northern hybridization experiments it is concluded that only one of the two
      cloned genes is transcribed in Anabaena cells growing on complete medium
      (containing ammonia). Under these conditions it appears that none of the other
      related sequences, not yet cloned, is transcribed. Transcription of only one
      member of the multigene family provides a possible explanation for the ability to
      isolate mutants resistant to the herbicide DCMU, whose target is believed to be
      the 32 kd protein. 

PMID- 24310438
TI  - Myocardial perfusion imaging with a cadmium zinc telluride-based gamma camera
      versus invasive fractional flow reserve.
AB  - PURPOSE: Recently introduced ultrafast cardiac SPECT cameras with cadmium zinc
      telluride-based (CZT) detectors may provide superior image quality allowing
      faster acquisition with reduced radiation doses. Although the level of
      concordance between conventional SPECT and invasive fractional flow reserve (FFR)
      measurement has been studied, that between FFR and CZT-based SPECT is not yet
      known. Therefore, we aimed to assess the level of concordance between CZT SPECT
      and FFR in a large patient group with stable coronary artery disease. METHODS:
      Both invasive FFR and myocardial perfusion imaging with a CZT-based SPECT camera,
      using Tc-tetrofosmin as tracer, were performed in 100 patients with stable angina
      and intermediate grade stenosis on invasive coronary angiography. A cut-off value
      of <0.75 was used to define abnormal FFR. RESULTS: The mean age of the patients
      was 64 +/- 11 years, and 64 % were men. SPECT demonstrated ischaemia in 31 % of
      the patients, and 20 % had FFR <0.75. The concordance between CZT SPECT and FFR
      was 73 % on a per-patient basis and 79 % on a per-vessel basis. Discordant
      findings were more often seen in older patients and were mainly (19 %) the result
      of ischaemic SPECT findings in patients with FFR >= 0.75, whereas only 8 % had an
      abnormal FFR without ischaemia as demonstrated by CZT SPECT. CONCLUSION: Only 20 
      30 % of patients with intermediate coronary stenoses had significant ischaemia
      as assessed by CZT SPECT or invasive FFR. CZT SPECT showed a modest degree of
      concordance with FFR, which is comparable with previous results with conventional
      SPECT. Further investigations are particularly necessary in patients with normal
      SPECT and abnormal FFR, especially to determine whether these patients should
      undergo revascularization.

PMID- 24310439
TI  - Association between left ventricular regional sympathetic denervation and
      mechanical dyssynchrony in phase analysis: a cardiac CZT study.
AB  - PURPOSE: To evaluate the relationships among myocardial sympathetic innervation,
      perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc
      telluride (CZT) scintigraphy. METHODS: A group of 29 patients underwent an
      evaluation of myocardial perfusion with (99m)Tc-tetrofosmin CZT scintigraphy and
      adrenergic innervation with (123)I-metaiodobenzylguanidine (MIBG) CZT
      scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening
      score (STS), as well as the summed (123)I-MIBG defect score (SS-MIBG), were
      determined. Regional tracer uptake for both (99m)Tc-tetrofosmin and (123)I-MIBG
      was also calculated. Finally, the presence of significant myocardial mechanical
      dyssynchrony was evaluated in phase analysis on gated CZT images and the region
      of latest mechanical activation identified. RESULTS: Significant mechanical
      dyssynchrony was present in 17 patients (59 %) and associated with higher SRS (P
      = 0.030), SMS (P < 0.001), STS (P = 0.003) and early SS-MIBG (P = 0.037) as well
      as greater impairments in left ventricular ejection fraction (P < 0.001) and end
      diastolic volume (P < 0.001). In multivariate analysis a higher end-diastolic
      volume remained the only predictor of mechanical dyssynchrony (P = 0.047).
      Interestingly, while in the whole population regional myocardial perfusion and
      adrenergic activity were strongly correlated (R = 0.68), in patients with
      mechanical dyssynchrony the region of latest mechanical activation was predicted
      only by greater impairment in regional (123)I-MIBG uptake (P = 0.012) that
      overwhelmed the effect of depressed regional perfusion. CONCLUSION: Left
      ventricular mechanical dyssynchrony is associated with greater depression in
      contractile function and greater impairments in regional myocardial perfusion and
      sympathetic activity. In patients with dyssynchrony, the region of latest
      mechanical activation is characterized by a significantly altered adrenergic
      tone.

PMID- 24310440
TI  - Long-term results of the Er-Yag laser used in stapes surgery.
AB  - Stapes surgery is performed using both conventional techniques and a variety of
      laser systems. The Er-Yag laser is a type of pulsation laser deemed by many to be
      the safest for ear surgery. The aim of this study was to assess the long-term
      effects of using the Er-Yag laser in stapes surgery and its impact on inner ear
      function. The study was conducted on 95 ears (48 right and 47 left) that had
      undergone Er-Yag laser-assisted stapedotomy. The follow-up time was at least 3
      years. Pure tone audiometry was performed on all patients. The frequency ranged
      from 125 to 8,000 Hz. Air conduction and bone conduction were both assessed.
      Moreover, all patients had their stapedius reflex assessed and were given a Rinne
      test. The results were evaluated according to the Committee on Hearing and
      Equilibrium guidelines and then statistically analyzed using the Wilcoxon
      sequence pair test with a p value of <0.05. A decrease in the hearing threshold
      of 0.5, 1, and 3 kHz, for both bone and air conduction was observed for all
      patients (p < 0.0001). The Wilcoxon sequence pair test revealed a statistically
      significant correlation between the pre- and postoperative treatment mean air
      bone gap values (p < 0.0001). No facial nerve paralysis was observed. No Er-Yag
      laser side effects were observed on inner ear function. The patients also had
      lower hearing thresholds. These observations demonstrate the usefulness of Er-Yag
      lasers in stapes surgery.

PMID- 24310441
TI  - Promoting transboundary animal disease risk management via a multiple health and
      husbandry intervention strategies in upland Lao PDR.
AB  - Surveys of smallholder farmer knowledge, attitude, practice (KAP) and income were
      conducted in 2011 and 2012 in five northern provinces of Lao People's Democratic
      Republic (Lao PDR; n = 200 farmers). Participating villages were classified as
      either from a livelihood development project (LV; n = 80 farmers) or a livestock
      research project that contained both 'high-intervention' (HI; n = 60 farmers) or
      'low-intervention' (LI; n = 60 farmers) villages. Farmer training plus a suite of
      health and productivity interventions were implemented in HI sites; only
      vaccination was implemented in LI sites, whilst various interventions and limited
      vaccination were introduced to LV sites. Farmer interviews were conducted with
      survey questions on socioeconomic variables and KAP of large ruminant health and
      disease risk management, enabling determination of quantitative and dichotomous
      qualitative traits and comparison of results from HI, LI and LV villages. The
      average farmer income from sales of large ruminants in HI was USD 621, in LI was
      USD 547 and in LV was USD 225 (p < 0.001). The predicted mean of total knowledge
      scores (/42) in the 2012 survey in HI was 28, in LI was 22 and in LV was 17 (p <
      0.001). We conclude that improved KAP of large ruminant health and production can
      be achieved by intensive training, although with some farmers yet to apply their
      knowledge on husbandry and biosecurity practices, continued learning support and
      closed linkage of research and development projects to improve extension capacity
      is recommended. This multiple participatory approach promoting biosecurity in
      addition to vaccination may provide a more sustainable pathway for the
      advancement of Lao PDR on the Progressive Control Pathway for foot and mouth
      disease control.

PMID- 24310442
TI  - Recent advances in moyamoya disease: pathophysiology and treatment.
AB  - Moyamoya disease is a progressive intracranial arteriopathy characterized by
      bilateral stenosis of the distal portion of the internal carotid artery and the
      proximal anterior and middle cerebral arteries, resulting in transient ischemic
      attacks or strokes. The pathogenesis of moyamoya disease remains unresolved, but
      recent advances have suggested exciting new insights into a genetic contribution
      as well as into other pathophysiological mechanisms. Treatment that may halt
      progression of the disease or even reverse the intracranial arteriopathy is yet
      to be found. There are strong indications that neurosurgical intervention,
      through direct, indirect, or combined revascularization surgery, can reduce the
      risk of ischemic stroke and possibly also cognitive dysfunction by improving
      cerebral perfusion, although randomized clinical trials have not been performed.
      Many questions regarding the indication for and timing of surgery remain
      unanswered. In this review, we discuss recent developments in the pathogenesis
      and treatment of moyamoya disease. 

PMID- 24310443
TI  - Amplitude-integrated EEG and range-EEG modulation associated with pneumatic
      orocutaneous stimulation in preterm infants.
AB  - OBJECTIVE: Controlled somatosensory stimulation strategies have demonstrated
      merit in developing oral feeding skills in premature infants who lack a
      functional suck, however, the effects of orosensory entrainment stimulation on
      electrocortical dynamics is unknown. The objective of the study was to determine
      the effects of servo-controlled pneumatic orocutaneous stimulation presented
      during gavage feedings on the modulation of amplitude-integrated
      electroencephalogram (aEEG) and range electroencephalogram (rEEG) activity. STUDY
      DESIGN: Two-channel EEG recordings were collected during 180 sessions that
      included orocutaneous stimulation and non-stimulation epochs among 22 preterm
      infants (mean gestational age=28.56 weeks) who were randomized to treatment and
      control 'sham' conditions. The study was initiated at around 32 weeks post
      menstrual age. The raw EEG was transformed into aEEG margins, and rEEG amplitude
      bands measured at 1-min intervals and subjected to a mixed models statistical
      analysis. RESULT: Multiple significant effects were observed in the processed EEG
      during and immediately following 3-min periods of orocutaneous stimulation,
      including modulation of the upper and lower margins of the aEEG, and a
      reorganization of rEEG with an apparent shift from amplitude bands D and E to
      band C throughout the 23-min recording period that followed the first stimulus
      block when compared with the sham condition. Cortical asymmetry also was apparent
      in both EEG measures. CONCLUSION: Orocutaneous stimulation represents a salient
      trigeminal input, which has both short- and long-term effects in modulating
      electrocortical activity, and thus is hypothesized to represent a form of neural
      adaptation or plasticity that may benefit the preterm infant during this critical
      period of brain maturation.

PMID- 24310444
TI  - Frequency-modulated orocutaneous stimulation promotes non-nutritive suck
      development in preterm infants with respiratory distress syndrome or chronic lung
      disease.
AB  - OBJECTIVE: For the premature infant, extrauterine life is a pathological
      condition, which greatly amplifies the challenges to the brain in establishing
      functional oromotor behaviors. The extent to which suck can be entrained using a
      synthetically patterned orocutaneous input to promote its development in preterm
      infants who manifest chronic lung disease (CLD) is unknown. The objective of this
      study was to evaluate the effects of a frequency-modulated (FM) orocutaneous
      pulse train delivered through a pneumatically charged pacifier capable of
      enhancing non-nutritive suck (NNS) activity in tube-fed premature infants. STUDY
      DESIGN: A randomized trial to evaluate the efficacy of pneumatic orocutaneous
      stimulation 3 * per day on NNS development and length of stay (LOS) in the
      neonatal intensive care unit among 160 newborn infants distributed among three
      sub-populations, including healthy preterm infants, respiratory distress syndrome
      (RDS) and CLD. Study infants received a regimen of orocutaneous pulse trains
      through a PULSED pressurized silicone pacifier or a SHAM control (blind pacifier)
      during gavage feeds for up to 10 days. RESULT: Mixed modeling, adjusted for the
      infant's gender, gestational age, postmenstrual age and birth weight, was used to
      handle interdependency among repeated measures within subjects. A significant
      main effect for stimulation mode (SHAM pacifier vs PULSED orosensory) was found
      among preterm infants for NNS bursts per min (P=0.003), NNS events per min
      (P=0.033) and for total oral compressions per min (NNS+nonNNS) (P=0.016).
      Pairwise comparison of adjusted means using Bonferroni adjustment indicated RDS
      and CLD infants showed the most significant gains on these NNS performance
      indices. CLD infants in the treatment group showed significantly shorter LOS by
      an average of 2.5 days. CONCLUSION: FM PULSED orocutaneous pulse train stimuli
      delivered through a silicone pacifier are effective in facilitating NNS burst
      development in tube-fed RDS and CLD preterm infants, with an added benefit of
      reduced LOS for CLD infants.

PMID- 24310445
TI  - Does multiple gestation impact birthweight deficit from smoking?
AB  - OBJECTIVE: To test the hypothesis that the combined birthweight deficit from
      smoking in twin gestation is significantly greater than previously described for
      singletons. STUDY DESIGN: Retrospective cohort study of White/Black live-born
      twins, 32 to 40 weeks of gestation, 1990 to 2005, Kansas City, MO. Data were
      analyzed by t-test, chi(2), linear and linear regression analyses. RESULT: The
      cohort comprised 1190 twin pairs, 58% Whites and 55% >=37 weeks. Smoking rate was
      14.5% and similar by race (14.2% White vs 14.8%, P=0.772). The aggregate
      birthweight of twins of nonsmokers was greater, 5116 g +/- 25 g vs 4870 g +/- 59
      g, P<0.001 (mean+/-s.d.) and the difference was 264 g (95% confidence interval,
      156 to 372 g) after adjusting for other variables in linear regression analyses.
      CONCLUSION: Smoking-associated growth restriction in twins is quantitatively
      similar to that of singletons. This finding is suggestive of dissipation or a
      ceiling effect to the growth-restricting effect of cigarette smoking.

PMID- 24310446
TI  - Is variation in total antioxidant capacity of human milk associated with levels
      of bio-active proteins?
AB  - OBJECTIVE: As the antioxidant properties of human milk may be beneficial for very
      preterm-born infants, it is important to identify the association between total
      antioxidant capacity (TAC) and bio-active proteins. STUDY DESIGN: Breast milk was
      prospectively collected (four times) on postpartum days 6 to 8, 13 to 15, 20 to
      22 and 27 to 29 from 15 mothers who had delivered between 24 and 31 weeks of
      gestation. Skimmed milk was assayed to measure TAC and bio-active proteins
      (lysozyme, lactoferrin, leptin and adiponectin). The association between TAC and
      levels of bio-active proteins during the first month of lactation was analyzed in
      a regression model. RESULT: Coefficient of determinations (R(2)) revealed an
      overall effect of bio-active proteins on breast milk TAC (R(2)=0.635+/-0.102,
      P<0.0001). Breast milk leptin, lysozyme and lactoferrin levels were identified as
      independent factors that significantly predict the concentration of TAC.
      CONCLUSION: The identified enhancement of the antioxidant capacity of human milk
      by bio-active proteins that are lacking in commercial formula supports
      consideration of breast milk as ideal nutrition for preterm-born neonates.

PMID- 24310447
TI  - Ultrasound-driven preparation and pair distribution function-assisted structure
      solution of a copper-based layered coordination polymer.
AB  - Nanoparticles of a copper-based layered coordination polymer, STAM-2, have been
      prepared via an ultrasound mediated transformation from a layered metal-organic
      framework, STAM-1. The structure of the material was then solved using pair
      distribution function analysis to identify the structural units present and the
      final structural model refined against the pair distribution function data. 

PMID- 24310448
TI  - Ion enrichment on the hydrophobic carbon-based surface in aqueous salt solutions
      due to cation-pi interactions.
AB  - By incorporating cation-pi interactions to classic all-atoms force fields, we
      show that there is a clear enrichment of Na(+) on a carbon-based pi electron-rich
      surface in NaCl solutions using molecular dynamics simulations. Interestingly,
      Cl(-) is also enriched to some extend on the surface due to the electrostatic
      interaction between Na(+) and Cl(-), although the hydrated Cl(-)-pi interaction
      is weak. The difference of the numbers of Na(+) and Cl(-) accumulated at the
      interface leads to a significant negatively charged behavior in the solution,
      especially in nanoscale systems. Moreover, we find that the accumulation of the
      cations at the interfaces is universal since other cations (Li(+), K(+), Mg(2+),
      Ca(2+), Fe(2+), Co(2+), Cu(2+), Cd(2+), Cr(2+), and Pb(2+)) have similar
      adsorption behaviors. For comparison, as in usual force field without the proper
      consideration of cation-pi interactions, the ions near the surfaces have a
      similar density of ions in the solution. 

PMID- 24310449
TI  - Supportive treatment for children with the common cold.
AB  - PURPOSE OF REVIEW: This review summarizes recent developments in the supportive
      treatment of common cold symptoms in children. RECENT FINDINGS: Conventional
      common cold therapies are no longer recommended for use in young children because
      of safety concerns. There are no studies that convincingly demonstrate the
      efficacy of any therapy for treatment of common cold symptoms in children less
      than 6 years of age and it is unlikely studies that establish efficacy can be
      done. Recent studies report a significant effect of probiotics on the occurrence
      of common cold illnesses in children, and studies in animals provide a plausible
      mechanism of action. These data suggest that the use of probiotics may have
      promise for the prevention of common cold illnesses in children. SUMMARY: The
      effect of treatment on the severity of common cold symptoms cannot be accurately
      assessed with current study designs. In the absence of convincing evidence of
      efficacy, treatment of young children with symptomatic therapies cannot be
      recommended. Preliminary data suggest a small, beneficial effect of probiotics
      for the prevention of common cold illness.

PMID- 24310450
TI  - TGF-betas and Smads activities at the site of failed neural tube in the human
      embryos.
AB  - AIM: Transforming growth factor beta (TGF-beta) and Smads control intracellular
      signaling pathways in neurulation. Although previously reported similar
      experimental animal studies, the aim of this human study is to investigate the
      expression of TGF-beta (1,2,3) and Smads (1,2,3,6,7) in aborted human fetuses
      with myeloschisis. MATERIAL AND METHODS: Twelve human fetuses with neural tube
      defect were obtained. They were stained with antibodies against TGF-beta1, TGF
      beta2, TGF-beta3, Smad (1,2,3), Smad 6 and Smad 7 using the indirect
      immunohistochemical technique. RESULTS: We noted mild immune reactivity of TGF
      beta1 and TGF-beta2 in the open neural plate, motor neurons and surrounding
      tissue. Strong immune reactivity of TGF-beta3 was shown in only open neural plate
      and surrounding tissue. Immunoreactivity of all Smads noted negative except
      Smad7. CONCLUSION: These results suggested at the site where the neural tube
      failed to close, TGF-beta 1,2 and Smads 1,2,3,6 do not continue their activity
      and decrease with internal timing of embryonic development. Additionally
      ectodermal layers are considered by embryo as "not closed wound" and TGF-beta3
      activity may be an effort to repair the failed closure.

PMID- 24310451
TI  - Clinicopathological characteristics of chordoma: an institutional experience and
      a review of the literature.
AB  - AIM: To study the clinicopathologic characteristics of chordomas from a single
      institution. MATERIAL AND METHODS: This study is a retrospective analysis of 18
      cases of chordomas diagnosed over a period of 5-years at Sher-i-Kashmir Institute
      of Medical Sciences, Srinagar, from 2006 to 2010. RESULTS: The overall mean age
      of the patients was 46.72 years. Males outnumbered females. Sacrum was the
      commonest site involved. Histopathologically, the majority of cases were
      conventional chordoma with four cases of chondroid variety. There was a single
      case of dedifferentiated chordoma that presented with bone metastasis. Most
      patients did well after surgery and radiotherapy. One patient had a local
      recurrence and one patient with dedifferentiated variant died on follow-up.
      CONCLUSION: Though locally aggressive, chordomas are effectively treated with
      resection and postoperative radiotherapy.

PMID- 24310452
TI  - The effect of electromagnetic radiation on the rat brain: an experimental study.
AB  - AIM: The aim of this study is to determine the structural changes of
      electromagnetic waves in the frontal cortex, brain stem and cerebellum. MATERIAL
      AND METHODS: 24 Wistar Albino adult male rats were randomly divided into four
      groups: group I consisted of control rats, and groups II-IV comprised
      electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of
      the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per
      day for 2 months. RESULTS: While the histopathological changes in the frontal
      cortex and brain stem were normal in the control group, there were severe
      degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in
      the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative
      Capacity level was significantly decreased in the EMR groups and also Total
      Oxidative Capacity and Oxidative Stress Index levels were significantly increased
      in the frontal cortex, brain stem and cerebellum. IL-1beta level was
      significantly increased in the EMR groups in the brain stem. CONCLUSION: EMR
      causes to structural changes in the frontal cortex, brain stem and cerebellum and
      impair the oxidative stress and inflammatory cytokine system. This deterioration
      can cause to disease including loss of these areas function and cancer
      development.

PMID- 24310453
TI  - Diagnosis and treatment of traumatic internal carotid artery pseudoaneurysm
      primarily manifested by repeated epistaxis.
AB  - AIM: The current study aims to explore the diagnosis and treatment of traumatic
      internal carotid artery pseudoaneurysm (TICAP) primarily manifested by repeated
      epistaxis. MATERIAL AND METHODS: Clinical data from 31 patients suffering from
      repeated epistaxis after trauma were retrospectively analyzed. All patients were
      diagnosed definitely with pseudoaneurysm at the internal carotid cavernous sinus
      segment by digital subtract angiography (DSA). RESULTS: Endovascular
      interventional therapy was performed for all the patients. 20 patients received
      direct occlusion of the parent artery by embolization with detachable balloons
      and the rest received covered stent implantation to cover the parent arterial
      tear. No death occurred. Epistaxis did not recur after operation. CONCLUSION: DSA
      is the gold standard for TICAP diagnosis. Endovascular interventional therapy is
      the treatment of choice for TICAP. Compared with internal carotid artery
      occlusion with balloons, covered stent implantation is a more valuable
      endovascular intervention method.

PMID- 24310454
TI  - The experimental study of miRNA in pituitary adenomas.
AB  - AIM: We investigated the differential miRNA expression in pituitary adenomas
      (both non-functioning and gonadotropin-secreting) and normal pituitaries.
      MATERIAL AND METHODS: RNA was extracted and purified from pituitary adenomas (10
      non-functioning and 10 gonadotropin-secreting) and from two normal pituitary
      tissue samples. The samples were analyzed by miRNA microarray. Gene expression
      was measured using realtime RT-PCR with SYBR GREEN I. RESULTS: In non-functioning
      pituitary adenomas, 25 miRNA genes were up-regulated (six by over 5-fold) and 15
      were down-regulated (six by more than 10-fold). miR-124a was the most up
      regulated gene (38.58-fold), and miR-31 the most down-regulated gene (21.5-fold).
      In gonadotropin-secreting pituitary adenomas, 16 miRNA genes were up-regulated
      (six by over 4-fold) and 13 were down-regulated (seven by more than 10-fold). miR
      10b was the most up-regulated gene (48.73-fold), and miR-503 the most down
      regulated gene (39.8-fold). Five genes were up-regulated in both subtypes: miR
      523, miR-10b, miR-520b, miR-422a, and miR-422b. The RT-PCR results were
      consistent with those of the gene chips. CONCLUSION: We established miRNA
      expression maps of non-functioning and gonadotropin-secreting pituitary adenomas.
      The most strongly differentially expressed genes were miR-124a and miR-31 in non
      functioning pituitary adenomas, and miR-10b and miR-503 in gonadotropin-secreting
      pituitary adenomas.

PMID- 24310455
TI  - Mass lesions in the brain: tumor or multiple sclerosis? Clinical and imaging
      characteristics and course from a single reference center.
AB  - AIM: In demyelinating disease spectrum, tumor-like (tumefactive) demyelinating
      lesions (TDL) are rarely seen. Atypical imaging and clinical features of these
      lesions may cause misdiagnosis of tumor or abscess. MATERIAL AND METHODS: 25
      patients with TDL in our center were followed and clinical, magnetic resonance
      imaging (MRI), magnetic resonance spectroscopy, cerebrospinal fluid (CSF)
      findings and disease course were retrospectively evaluated. RESULTS: Mean age at
      symptom onset was 29 years. Motor and sensory deficits were most common symptoms
      and 18 of them were polysymptomatic. Mostly frontal and parietal regions were
      affected. 10/25 patients were initially misdiagnosed clinically as brain abscess,
      primary central nervous system tumor metastasis. T2-hypointense rim, incomplete
      ring enhancement of the lesions on post-gadolinium T1- weighted imaging on brain
      MRI enabled accurate diagnosis of TDLs. 13 of 21 patients with first-TDL
      presentation sustained a monophasic course, remaining 8 patients converted to
      multiple sclerosis (MS) at a mean 38.4 months follow-up. Clinical isolated
      syndrome (CIS) patients were older than patients who developed MS and Expanded
      Disability Status Scale was lower (0.96 vs 3.7). CONCLUSION: Although MRI, CSF
      and pathologic examination help in differential diagnosis of the mass lesions,
      close follow-up is still crucial for the definite diagnosis. A higher MS
      conversion rate was found in patients with a younger TDL onset age.

PMID- 24310456
TI  - Using an autologous fibrin sealant in the preventing of cerebrospinal fluid leak
      with large skull base defect following endoscopic endonasal transsphenoidal
      surgery.
AB  - AIM: Postoperative cerebrospinal fluid (CSF) leak following endoscopic endonasal
      transsphenoidal surgery (EETS) is associated with increased morbidity and
      mortality. This prospective study is the first evaluation of using autologous
      fibrin sealant for preventing postoperative CSF leak and related complications.
      MATERIAL AND METHODS: 200 endoscopic endonasal transsphenoidal approaches were
      included in the study and reviewed retrospectively from September 2010 to June
      2012. A total of 55 patients who have large skull base and diafragma sella
      defects, connected with basal cisterns or ventricles, were chosen for the study.
      The patients were operated via extended or classical endoscopic endonasal
      transsphenoidal approach. The skull base has been repaired using AFS combined
      with multilayer reconstruction in all cases. The incidence of CSF leak as a
      complication of EETS was analyzed. RESULTS: The ages of the patients ranged from
      20 to 83 years (mean 49.3 years). There were 25 (46%) male patients and 30 (54%)
      females. All patients had tumors with suprasellar or parasellar extension.
      Postoperative CSF leak was determined in 2 patients (3.6%). There were no
      complications and allergic reactions associated with the use of AFS. CONCLUSION:
      Using of AFS combined with multilayer reconstruction technique is a safe and
      effective method to prevent CSF leak in large defects following EETS.

PMID- 24310457
TI  - Evaluation of the effects of mobile phones on the neural tube development of
      chick embryos.
AB  - AIM: The objective of this study is to examine the effects of radiation of mobile
      phones on developing neural tissue of chick embryos. MATERIAL AND METHODS: There
      were 4 study groups. All Groups were placed in equal distance, from the mobile
      phones. Serial sections were taken from each Group to study the neural tube
      segments. RESULTS: The TUNEL results were statistically significant (p < 0.001)
      at 30 and 48 hours in the third Group. We found low Bcl-2 levels partly in Group
      4 and increased activity in Group 3. Caspase-3 was negative in the 48 and 72
      hours in the Control Group, had moderate activity in the third Group 3, weak
      activity in the 48 hour, and was negative in the 72 hour in other groups. Caspase
      9 immunoreactivity was weak in Group 1, 2 and 3 at 30 hours and was negative in
      Group 1 and 4 at 48 and 72 hours. Caspase-9 activity in the third Group was weak
      in all three stages. CONCLUSION: Electromagnetic radiation emitted by mobile
      phones caused developmental delay in chick embryos in early period. This finding
      suggests that the use of mobile phones by pregnant women may pose risks.

PMID- 24310458
TI  - Management of medically intractable genitofemoral and ilioingunal neuralgia.
AB  - AIM: To evaluate the effectiveness of invasive procedures in medically
      intractable genitofemoral and ilioingunal neuralgia. MATERIAL AND METHODS: This
      is a prospective study of 20 patients with genitofemoral and ilioinguinal
      neuralgias who were treated at our medical center between 2007 and 2011.
      Genitofemoral and ilioinguinal nerve blocks were performed in all cases after
      medical treatment had failed to alleviate the patients' pain. Neurectomy was
      performed for the patients whose pain did not improve. Patient histories,
      physical examinations and visual analogue scale scores before and after
      treatments were analyzed. RESULTS: Fourteen (70%) of the patients were treated
      with nerve blocks and six (30%) of the patients whose pain did not improve with
      nerve block application underwent neurectomy which resulted in pain relief.
      CONCLUSION: For patients with medically intractable genitofemoral and
      ilioinguinal neuralgias, nerve blocks and neurectomies can be applied safely for
      pain control.

PMID- 24310459
TI  - Evaluation of the prevertebral soft tissue thickness by magnetic resonance
      imaging in patients with mild neck problem.
AB  - AIM: We encountered no study conducted on the evaluation of prevertebral soft
      tissue (PVST) thickness by magnetic resonance imaging (MRI) during our literature
      search. Measuring PVST thickness by MRI in the cervical region of adult cases was
      aimed in the present retrospective study. MATERIAL AND METHODS: For the intended
      purpose, a total of 136 patients, composed of both males and females, with ages
      ranging from 20 to 69 years, in whom no pathology in the cervical prevertebral
      region was revealed by MRI modality implemented for various reasons, were
      included in the study. RESULTS: The upper limit of normal for PVST thickness was
      measured in our study to be 10 mm, 7 mm and 20 mm at C1, C2-C3 and C6-C7
      vertebral levels, respectively. The least variation in the measurements and
      standard deviations were obtained at C3-C4 vertebral levels. Upon making a
      comparison between the measured PVST thicknesses on the basis of gender, the
      measurements at C2,C4 and C7 were found to display significant difference,
      whereas that was not the case for the measurements obtained at the other levels.
      CONCLUSION: Progressively widespread use of MRI for the traumas inflicting the
      cervical region makes it obligatory to specify normal values for the thickness of
      PVST measured by MRI.

PMID- 24310460
TI  - The effects of lornoxicam on neuroprotection following diffuse traumatic brain
      injury in rats.
AB  - AIM: In this study, the effects of lornoxicam on the prevention of secondary
      brain injury via the apoptotic pathway were studied in a rat model of head
      injury. MATERIAL AND METHODS: Thirty adult male Wistar albino rats were
      anesthetized, and experimental closed head trauma was induced by allowing a 450 g
      weight to fall two meters onto a metallic disk fixed to the intact skull. After
      head injury, the rats were randomly divided into two groups: Group I (n=15) rats
      were administered 2 mL saline intraperitoneally (controls); Group II (n=15) rats
      were administered 2 mL 1.3 mg kg-1 lornoxicam intraperitoneally. Brain tissue
      samples were divided into two pieces by interhemispheric incision for biochemical
      and histological analysis. RESULTS: TUNEL positivity was seen in neuroglia cells
      of the brain cortex in both groups. While the immunoreactivities of caspase 8, 9
      and Fas/ Fas ligand were similar in both groups, the immunoreactivity of caspase
      3 was greater in Group I than Group II. MDA was significantly lower in Group II
      than in Group I (p < 0.05). The decrease in SOD level was higher in Group I than
      Group II. CONCLUSION: Lornoxicam did not prevent apoptosis in this rat model of
      brain trauma but causes a decrease.

PMID- 24310461
TI  - 3.0-T diffusion images after clipping of middle cerebral artery aneurysm.
AB  - AIM: Replacement of aneurysm clips or temporary parent artery occlusion during
      aneurysm clipping (AC) carries the risk of inducing postoperative neurologic
      deficits. When studying the risk of surgical complications associated with
      cerebral aneurysms, patients with similar conditions should be compared to
      eliminate the influence of rupture and location of aneurysm. MATERIAL AND
      METHODS: We used 3.0-Tesla (3.0T) magnetic resonance diffusion-weighted imaging
      (DWI) and magnetic resonance angiography (MRA) to analyze surgical complications
      after AC. A total of 42 AC procedures for 40 unruptured and 2 delayed-phase
      ruptured MCA aneurysms were evaluated. RESULTS: In six patients, temporary parent
      artery occlusion was performed. Asymptomatic hyperintensities were observed on
      DWI of three patients. In one patient, an asymptomatic lesion was most likely
      caused by a small contusion that occurred during dissection of an aneurysm
      attached to the brain surface. In two patients, asymptomatic cortical lesions
      were caused by brain surface contusions due to lacerations of the open dura. No
      symptomatic hyperintensities on DWI were observed after surgery. No fixed
      ischaemic neurologic deficits resulted from AC. CONCLUSION: Although some
      postoperative abnormalities were observed with 3.0T DWI, we found clipping of MCA
      aneurysms to be a safe procedure with a low risk of ischaemic complications.

PMID- 24310462
TI  - Implanting pedicle screw in fractured vertebra results in no adverse effect on
      bone healing in thoracic or lumbar burst fracture.
AB  - AIM: To confirm whether implanting pedicle-screw at the level of fractured
      vertebra increases adverse effects on fracture healing. MATERIAL AND METHODS: CT
      follow-up was conducted for 28 patients who sustained thoracic or lumbar burst
      fracture and underwent posterior pedicle-screw instrumentation and reduction
      including implanting screws into the fractured vertebra at the same time. The
      time for follow-up CT scan ranged from 1 to 3 years postoperatively. RESULTS: 28
      patients underwent final CT scan 1 to 3 years after surgery which revealed good
      bony fusion within each fractured vertebra and no screw or rod breakage; kyphosis
      was also not detected. CONCLUSION: Implanting pedicle-screw at the level of
      fractured vertebra does not have a negative influence on bone healing.

PMID- 24310463
TI  - The neuroprotective effects of rituximab in rat spinal cord injury model: an
      immunohistochemical study.
AB  - AIM: In the present study, we investigate the neuroprotective effects of
      rituximab, a monoclonal antibody directed towards B cell mediated humoral
      immunity, on a rat spinal cord injury (SCI) model with immunohistochemical
      methods. MATERIAL AND METHODS: Twenty-four rats were used for the study. Rats
      were divided as control, SCI, and rituximab-treated SCI groups. Intraperitoneal
      rituximab administration was performed on days 0, 3 and 5 in the third group.
      Rats were sacrificed 7 days after trauma. Antibodies against IL-1beta, IL-6, TNF
      alpha and CD20 were studied with the ELISA method together with electron
      microscopic analysis. RESULTS: It was found that rituximab suppressed
      oligodendrocytes at the phagocytic stage but was still inefficient for the
      regenerative phase. TNF-alpha expression was markedly increased in rats subjected
      to SCI and suppressed after rituximab treatment. Decreased CD20 expression was
      another prominent finding in rats under rituximab therapy. However, expressions
      of IL-1beta and IL-6 were both increased in glial cells without significant
      change after rituximab administration. CONCLUSION: TNF-alpha expression was
      augmented at the level of SCI both in neuronal and glial cells, particularly in
      oligodendrocytes. All were suppressed after rituximab administration and
      rituximab reduced CD20 expression both in neuronal and supportive glial cells
      which may be related to neural healing.

PMID- 24310464
TI  - How analgesia-sedation alters monocyte mCD14 and HLA-DR levels in patients
      undergoing cerebral angiography?
AB  - AIM: This study aims to evaluate how analgesia-sedation causes alterations of HLA
      DR and cytokines (IL-10 and IL-6) in patients undergoing cerebral angiography for
      several cerebral vascular diseases. MATERIAL AND METHODS: This study includes 41
      males who underwent cerebral angiography. The study sample was divided into two:
      Group I had 7 patients who did not receive and group II had 34 patients who
      received analgesia-sedation before cerebral angiography. A venous blood sample
      was collected before and after cerebral angiography. RESULTS: Analgesia-sedation
      caused significant increase CD4+ and CD19 T lymphocytes (p < 0.001) but group I
      showed significant increase in CD40, CD154, and MHC-II levels (p < 0.001) after
      cerebral angiography. CONCLUSION: We suggest that the effects of fentanyl and
      midazolam on the immune response are the reflection of the effects by the
      monocyte, mHLA-DR expression. In the future, depending on the immunological
      status of the patients, different anesthetic applications including the new
      anesthetic agents that will be able to decrease immune system suppression will be
      required.

PMID- 24310465
TI  - Subdural hematoma associated with skull and dural metastasis of gastric
      carcinoma: a case report.
AB  - Skull bone metastasis from the gastric cancer is a rare. We reported a 52-year
      old male proven to have stomach cancer and who underwent subtotal gastrectomy 5
      months previously. Within the past 2 weeks, he experienced headache and dizziness
      followed by weakness of the left lower limb. A diagnosis of right chronic
      subdural hematoma (SDH) was made, and a burr hole was performed for drainage of
      the hematoma. However, 5 days later, the patient had sudden loss of consciousness
      without external evidence of trauma to the head. An emergency computed tomography
      (CT) scan revealed a high-density lesion consistent with an acute SDH on the
      right side. Histologically, metastasis of gastric adenocarcinoma was detected in
      both the dura mater and skull. It is suggested that the SDH was caused by the
      rupture of vessels in the metastasis or rupture of the inner dural vessels,
      possibly resulting from congestion of the outer vessels. 

PMID- 24310466
TI  - Spinal epidermoid cyst formation after spinal fracture operation: a case report.
AB  - Acquired spinal epidermoid cysts are extremely rare. There are only a few reports
      on the formation of epidermoid cysts after lumbar puncture or spinal trauma. In
      this report, we present a patient who was diagnosed with epidermoid cyst after
      operation for spinal fracture. This 43-year old female suffered from
      progressively worsening low back pain radiating down the left leg four years
      after lumbar burst fracture in the L1 segment and subsequent posterior vertebral
      pedicle screw fixation surgery. 1 year later, the spinal fracture fixation
      devices were successfully removed. On admission, spinal magnetic resonance
      imaging found a cyst locating anterior to the site of operation and this lesion
      was removed by a following total laminectomy. To the best of our knowledge, this
      is the first case ever reported showing the formation of epidermoid cyst after
      primary spinal fracture operation. Therefore, in patients with a history of
      spinal fracture operation, spinal epidermoid cysts should be taken into
      consideration if the low back pain and radiculopathy were refractory.

PMID- 24310467
TI  - Video-assisted thoracoscopic surgery for migration of a Kirschner wire in the
      spinal canal: a case report and literature review.
AB  - Orthopedic wires and pins are regularly used for the treatment of dislocations
      and bone fractures. Migration of these metallic fixation devices into the spinal
      canal is an uncommon complication. We present a 35-year-old man who underwent
      thoracic spinal canal migration of a Kirschner wire. The patient had undergone
      treatment of acromioclavicular joint dislocation with Kirschner wire fixation.
      Two months after the operation, a chest radiograph showed a Kirschner wire in the
      thoracic cavity. Chest computed tomography (CT) showed the object extended
      transversely across the spinal canal. Emergency video-assisted thoracoscopic
      surgery (VATS) was successfully performed to remove the Kirschner wire without
      any complication. The patient made an uneventful recovery and was discharged on
      the seventh day after surgery. In our opinion, it is important to pay attention
      to the migration of metallic fixation devices. Surgical removal of such migrated
      devices is necessary for preventing disastrous consequences. VATS is a safe and
      effective treatment in such cases. 

PMID- 24310468
TI  - Rathke's cleft cyst with non-hemorrhagic rupture resulting in alteration of
      signal intensity for a short period: a case report.
AB  - In a case of 23-year-old female with Rathke's cleft cyst (RCC), unusual changes
      with size and morphology on computed tomography (CT) and magnetic resonance
      images (MRI) were noted in a short period of 3 weeks after spontaneous rupture.
      The CT noted that the intracystic isodensity was changed to hyperdensity. And MRI
      showed not only a decrease in size of the lesion but also changing from hypo- and
      hyperintensity in T1- and T2-weighted images to hyperintensity in both T1- and T2
      weighted images. The intraoperative findings disclosed that the cyst content was
      milky-like, but not hemorrhagic. We considered that the leakage of cyst content
      to the cerebrospinal fluid pathway caused not only inflammatory reaction but also
      waxing and waning of both the cyst size and intralesional protein concentration,
      which resulted in unusual changing CT and MR appearance. We should take into
      consideration that the nature of RCC can be altered by not only intracystic
      hemorrhage but also non-hemorrhagic rupture even for a short period. 

PMID- 24310469
TI  - A rare case of intracerebral hemorrhage due to arteriovenous malformation located
      at petrous portion of the temporal bone.
AB  - Primary intraosseous arteriovenous malformations (AVM) are not infrequently
      encountered. We report a case of intraosseous arteriovenous malformation arising
      in the left temporal bone. A 51-year-old male patient presented with loss of
      conscious. Computerized tomography displayed hematoma measuring 4 cm in diameter
      in the left temporal lobe. Digital subtraction angiography (DSA) showed that a
      temporal bone AVM supplied by all the branches of the external carotid artery and
      vertebral artery. Many treatment modalities can be considered for preoperative
      steps and/or for definitive treatment. We preferred embolisation for this
      vascular pathology. To the best of our knowledge this represents the first case
      of an intraosseous arteriovenous malformation located in the temporal bone. 

PMID- 24310470
TI  - 'Double skull' appearance due to calcifications of chronic subdural hematoma and
      cephalhematoma: a report of two cases.
AB  - Chronic subdural hematomas and cephalhematomas are known to become calcified in
      some patients. We present interesting cases of cephalhematoma in a child and
      calcified chronic subdural hematoma in an elderly lady with both getting
      calcified. The first patient was a 7 months male with calcified cephalhematoma
      who presented with cosmetic deformity of the skull but did not have any
      neurological deficits. The other patient was a 54-year-old lady with calcified
      chronic subdural hematoma who presented with one episode of seizure but did not
      have any neurological deficit. CT scan revealed calcification of the hematoma
      causing a double skull appearance in both patients. 

PMID- 24310471
TI  - Blue rubber bleb naevus syndrome and Chiari malformation: high risk of
      peroperative haemorrhage.
AB  - Blue rubber bleb naevus syndrome is an uncommon disorder whereby patients possess
      cutaneous vascular malformations. Cranial malformations have been rarely reported
      in the literature. We report the first ever case of a patient with blue rubber
      bleb naevus syndrome (BRBNS), who was found to have a symptomatic Chiari
      malformation and prominent subcutaneous vascular malformations in communication
      with the intracranial venous sinuses. In our case, a routine operation for Chiari
      malformation was complicated by significant blood loss. The operative hazards are
      presented along with suggested peri-operative management strategies when carrying
      out neurosurgical operations on patients with BRBNS. A brief literature review is
      included. 

PMID- 24310472
TI  - Free floating ventricular shunt catheter between lateral ventricles: a case
      report of an unusual ventriculoperitoneal shunt complication.
AB  - Ventriculoperitoneal (VP) shunt proximal tip disconnection is rarely seen as a
      shunt complication. Shunt dysfunction and hydrocephaly can develop due to this
      disconnection. Presented here is a case of a disconnection of the ventricular
      catheter from the shunt valve, which passed between both lateral ventricles by
      free floating in the brain CT. The patient was operated on for hydrocephaly. The
      dysfunctional shunt valve and peritoneal catheter were removed and a new VP shunt
      system was implemented. Although some publications report that the ventricular
      catheter can be disconnected from the shunt valve, can adhere to the
      intraventricular structures, and can be a source of infection, no studies similar
      to the current case were found in the literature reporting a free floating
      ventricular catheter between the lateral ventricles. 

PMID- 24310473
TI  - Multiple extracranial metastases from secondary glioblastoma: a case report and
      review of the literature.
AB  - Glioblastoma represents extreme anaplasia in astrocytic tumors. In spite of this
      aggressiveness, extracranial metastasis of glioblastoma is very rare and has been
      documented in only a few patients in the literature. In this article, a 30-year
      old woman with secondary glioblastoma associated with extracranial distant
      metastasis was presented. In September 2008, an intracranial lesion in the left
      frontal region was diagnosed by magnetic resonance imaging (MRI) after admission
      to the hospital by headache and seizure and subsequently resected. The histology
      of the lesion revealed an anaplastic astrocytoma (grade III). Upon recurrence of
      the tumor 7 months later, the patient underwent a second craniotomy for
      recurrence tumor resection. The histological diagnosis was glioblastoma. After
      radiotherapy and chemotherapy, cranial computerized tomography (CT) and whole
      body scintigraphy revealed metastatic lesions in the right cervical lymph nodes
      and the left ischium. A neck dissection and parathyroidectomy on the right side
      was performed. The cytomorphological and histological features of the tumor
      supported the diagnosis of metastatic glioblastoma. 

PMID- 24310474
TI  - Primary glioblastoma of the medulla spinalis: a report of three cases and review
      of the literature.
AB  - Primary spinal glioblastoma multiforme (spinal GBM) is not a very common entity.
      This paper presents an outline of this rare neoplasm, its clinical presentation,
      course, management and outcome and reports a 3-case series of spinal GBM. In this
      3-case series with spinal GBM, one of the patients was operated for
      hydrocephalous 10 months later following the tumor surgery and another patient
      had cerebral metastasis after the surgery. In the postoperative period, two of
      the cases received radiotherapy and one received combined radiotherapy and
      chemotherapy with steroid therapy together following the tumor surgery. The
      review of the pertinent literature has revealed that due to the scarcity of the
      reported cases of primary spinal GBMs, this issue requires a closer look. GBM
      behaves more aggressive in medulla spinalis than it behaves when it originates
      from cerebrum. It may disseminate to the cerebrum during its course and it may
      cause hydrocephalus due to this dissemination (metastasis). 

PMID- 24310475
TI  - Brain abscess developing in a non-operated spontaneous intracerebral haemorrhage:
      a case report and literature review.
AB  - Brain abscesses are a rare but potentially lethal neurological lesions, generally
      occurring after septic episodes in immunodeficient patients or complicating
      neurosurgical procedures. Even though they are known complications of surgically
      treated intracerebral haemorrhages (ICH), the presence of a brain abscess at the
      site of an untreated ICH is a rare event. Such cases may result from
      haematogenous spread from distant foci or contiguous sites and are often preceded
      by episodes of sepsis and local infection. Immunodeficiency, AIDS, age, diabetes
      mellitus and vitamin-K deficiency are predisposing factors. Abscess formation
      should be considered in case of clinical deterioration, headache, and any
      neurological deficit after febrile episodes. Early diagnosis with
      neuroradiological imaging, infection blood markers and microbiological
      identification of the causative pathogen is crucial for treatment with surgical
      drainage or excision and specific antibiotic therapy, which guarantee good
      outcome and long-term survival. In fact, while prompt diagnosis and treatment
      guarantee good outcome and long-term survival, morbidity and mortality are very
      high in case of misdiagnosis. We report a case of a 49-year old man presenting
      with a brain abscess 13 weeks after a spontaneous ICH, without previous episodes
      of sepsis and with a suspected septic arthritis 2 weeks after abscess drainage. 

PMID- 24310476
TI  - Variable origin and ramification pattern of the lateral femoral cutaneous nerve:
      a case report and neurosurgical considerations.
AB  - Variations in the anatomy of the lateral femoral cutaneous nerve (LFCN) have been
      reported in the literature. LFCN is vulnerable to injury during several surgical
      operations, therefore any surgeon intervening in the area should be familiar to
      its topographic variability. Lesion of the nerve leads to a condition known as
      "meralgia paresthetica". We present a cadaveric case of a variant LFCN where two
      LFCN branches were encountered arising from the lumbar plexus. In specific the
      anterior LFCN branch originated from the femoral nerve, whereas at the level of
      the inguinal ligament, four nerve branches were present. The existence of
      multiple LFCN branches could lead to diagnostic confusion in case of "meralgia
      paresthetica", while if the neurosurgeon is not aware of the potential
      variability during surgical decompression of the nerve, postoperative
      complications may occur. The supernumerary LFCN branches could be identified by
      ultrasound imaging and be used as optimum vascularized grafts for sensory nerve
      repair.

PMID- 24310477
TI  - Synthesis and properties of cycloparaphenylene-2,7-pyrenylene: a pyrene
      containing carbon nanoring.
AB  - The first synthesis of a pyrene-containing carbon nanoring,
      cyclo[12]paraphenylene[2]-2,7-pyrenylene ([12,2]CPPyr), is described. Through a
      sequence of stepwise macrocyclization using Pd and Ni catalysts followed by
      aromatization of L-shaped cyclohexane units afforded a [12,2]CPPyr in five steps
      from commercially available compounds. The UV-vis absorption and fluorescence
      spectra as well as TD-DFT calculations clarified the unique photophysical and
      electronic properties of the [12,2]CPPyr. 

PMID- 24310478
TI  - N-benzoate-N' salicylaldehyde ethynelediamine: a new fluorescent sensor for Zn2+
      ion by "off-on" mode.
AB  - Imbalance of zinc ion (Zn(2+)) in human body causes diseases like Alzheimer's and
      Parkinson's and therefore Zn(2+) estimation in biological fluids has diagnostic
      values. Fluorescence "off-on" sensors have advantages of high sensitivity and in
      situ application over other sensors. A new fluorescent "off-on" Zn(2+) sensor, N
      benzoate-N' salicylaldehyde ethynelediamine (L), has been synthesisied. In
      1:1(v/v) CH3OH:PBS (PBS = phosphate buffer solution), L shows ca. 20 times
      enhancement in fluorescence intensity on interaction with Zn(2+), due to snapping
      of photoinduced electron transfer (PET) process, which is selective over metal
      ions - Na(+), K(+), Ca(2+), Ni(2+), Cu(2+), Cd(2+), Hg(2+) and Pb(2+). These
      metal ions either individually or all together does not interfere the sensing
      ability of L towards Zn(2+). A 1:1 interaction between L and Zn(2+) ion with
      binding constant 10(4.25) has been established from spectroscopic data.

PMID- 24310479
TI  - Spectral and molecular modeling studies on hydroxybenzaldehydes with native and
      modified cyclodextrins.
AB  - The inclusion complexation of 2-hydroxy-3-methoxybenzaldehyde (2HMB), 4-hydroxy-3
      methoxybenzaldehyde (4HMB), 3,4-dimethoxybenzaldehyde (DMB) and 4-hydroxy-3,5
      dimethoxybenzaldehyde (HDMB) with alpha-CD, beta-CD, HP-alpha-CD and HP-beta-CD
      were carried out by UV-Visible, steady-state and time-resolved fluorescence and
      PM3 methods. All the benzaldehydes shows dual fluorescence in aqueous and CD
      mediums and 1:1 inclusion complexes were formed with CDs. PM3 geometry
      optimizations results indicate that the HDMB/CD complex is significantly more
      favorable than the other complexes. The negative enthalpy changes suggest that
      the inclusion complexation processes are spontaneous. The geometry of the most
      stable complex shows that methoxy/OH group of HMBs is entrapped in the less polar
      CD cavities, while the aldehyde group present in the upper part of the CDs
      cavities. 

PMID- 24310480
TI  - Hierarchical classification as relational framing.
AB  - The purpose of this study was to model hierarchical classification as
      contextually controlled, generalized relational responding or relational framing.
      In Experiment 1, a training procedure involving nonarbitrarily related
      multidimensional stimuli was used to establish two arbitrary shapes as contextual
      cues for 'member of' and 'includes' relational responding, respectively.
      Subsequently those cues were used to establish a network of arbitrary stimuli in
      particular hierarchical relations with each other, and then test for derivation
      of further untrained hierarchical relations as well as for transformation of
      functions. Resultant patterns of relational framing showed properties of
      transitive class containment, asymmetrical class containment, and unilateral
      property induction, consistent with conceptions of hierarchical classification as
      described within the cognitive developmental literature. Experiment 2 extended
      the basic model by using "fuzzy category" stimuli and providing a better
      controlled test of transformation of functions. Limitations and future research
      directions are discussed. 

PMID- 24310481
TI  - Linnaeus' Peloria: The history of a monster.
AB  - The so-called Peloria case has been discussed repeatedly in world literature
      since the discovery of the five-spurred Linaria in 1742 and its description by
      Linnaeus in 1744. In 1742 a young Uppsala botanist found a peculiar specimen of
      the common toad-flax (now named Linaria vulgaris L.) on an island in the
      Stockholm archipelago. The plant, which had spread vegetatively, possessed five
      spurs instead of one spur, a characteristic of the common toad-flax. The material
      was presented to Linnaeus, who became quite excited. The finding was contrary to
      his concept that genera and species had universally arisen through an act of
      original creation and remained unchanged since then. In a famous thesis of 1744,
      Linnaeus called the deviating plant 'Peloria', Greek for 'monster'. The case of
      pelorism was discussed later on by a great number of famous writers and
      scientists including, for example, Goethe, Darwin, Naudin, De Vries and Stubbe.
      Parallel types were found in numerous species of other genera and families. Such
      aberrant forms are caused by spontaneous mutation. The history, mode of origin,
      morphology, inheritance and distribution of different Peloria mutants are
      discussed in the paper. 

PMID- 24310482
TI  - Procedures for identifying S-allele genotypes of Brassica.
AB  - Procedures are described for efficient selection of: (1) homozygous and
      heterozygous S-allele genotypes; (2) homozygous inbreds with the strong self- and
      sib-incompatibility required for effective seed production of single-cross F1
      hybrids; (3) heterozygous genotypes with the high self- and sib-incompatibility
      required for effective seed production of 3- and 4-way hybrids.From reciprocal
      crosses between two first generation inbred (I1) plants there are three potential
      results: both crosses are incompatible; one is incompatible and the other
      compatible; and both are compatible. Incompatibility of both crosses is useful
      information only when combined with data from other reciprocal crosses. Each
      compatible cross, depending on whether its reciprocal is incompatible or
      compatible, dictates alternative reasoning and additional reciprocal crosses for
      efficiently and simultaneously identifying: (A) the S-allele genotype of all
      individual I1 plants, and (B) the expressions of dominance or codominance in
      pollen and stigma (sexual organs) of an S-allele heterozygous genotype.
      Reciprocal crosses provide the only efficient means of identifying S-allele
      genotypes and also the sexual-organ x S-allele-interaction types.Fluorescent
      microscope assay of pollen tube penetration into the style facilitates
      quantitation within 24-48 hours of incompatibility and compatibility of the
      reciprocal crosses. A procedure for quantitating the reciprocal difference is
      described that maximizes informational content of the data about interactions
      between S alleles in pollen and stigma of the S-allele-heterozygous genotype.Use
      of the non-inbred Io generation parent as a 'known' heterozygous S-allele
      genotype in crosses with its first generation selfed (I1) progeny usually reduces
      at least 7 fold the effort required for achieving objectives 1, 2, and 3,
      compared to the method of making reciprocal crosses only among I1
      plants.Identifying the heterozygous and both homozygous S-allele genotypes during
      the I1 generation facilitates, during subsequent inbred generations, strong
      selection for or against modifier genes that influence the intensity of self- and
      sib-incompatibility. Selection for strong self and sib incompatibility can be
      effective for both homozygous inbreds and also for the S-allele heterozygote,
      thus facilitating production of single-cross F1 hybrids and also of 3-and 4-way
      hybrids. 

PMID- 24310483
TI  - Doubled haploids for estimating genetic variances and a scheme for population
      improvement in self-pollinating crops.
AB  - An analysis is derived for a diallel experiment in which each cross is
      represented by a number of homozygous Unes developed by the doubled haploid
      method. Both additive and additive x additive genetic variances can be estimated
      with this analysis. A population-improvement scheme involving the doubled haploid
      or single seed descent methods is also proposed. 

PMID- 24310484
TI  - An interval estimation of expected response to selection.
AB  - A method is presented here for obtaining an interval estimate of expected
      response to selection based on results of a progeny test experiment. The
      structure of the constructed confidence limits is then examined for the influence
      of the numbers of lines and replicates on the precision of predicting the
      expected response to selection. 

PMID- 24310485
TI  - The duration of DNA synthetic (S) period in Zea mays: A genetic control.
AB  - The nuclear cycle among several diverse genetic stocks of Zea mays root meristem
      cells was compared and it was found that there were no significant differences
      among the nuclear cycle durations and its component phases. The durations of
      various periods of their mitotic cycles were studied by autoradiography of cells
      pulse-labelled with tritiated thymidine (3H-TdR). The total nuclear cycle was 10
      to 11.5 hours and mitosis was 0.81 to 1.34 hours at 25 degrees C. The S period is
      the longest interval (50% of the total time) of the nuclear cycle; of the rest of
      the cycle, G2 is longer than G1 or mitosis among all stocks. The constancy of the
      nuclear cycle among several stocks was adduced as evidence for strict genetic
      control of the cycle. Furthermore, it is demonstrated the DNA synthesis period is
      not dependent upon the amount of DNA present. 

PMID- 24310486
TI  - Adolescent discipline: Different family members' perception.
AB  - Adolescence is perhaps the most difficult period of child rearing for parents.
      This study attempted to identify disciplinary techniques used by parents as
      perceived by mothers, fathers, and their adolescent children. Results indicated
      several significant areas of intrafamilial disagreement in regard to disciplinary
      techniques utilized, although all subjects tended to agree that some form of
      verbal reasoning was the primary disciplinary technique utilized with these
      adolescents. 

PMID- 24310487
TI  - The demographic correlates of admissions to the child and adolescent inpatient
      clinic at a midwestern metropolitan mental health complex.
AB  - Using the data from the 1970 census of population and housing for the Standard
      Metropolitan Statistical Area (SMSA) of Milwaukee, Wisconsin, demographic
      information was recorded for each of the approximately 300 census tracts in the
      Milwaukee County pertaining to population characteristics, marital status, age
      stratification, economic characteristics, and housing characteristics. Also,
      information was collected on number of admissions into the child and adolescent
      inpatient clinic for each census tract. The 300 census tracts were then divided
      into four categories: very low admission, low admission, high admission, and very
      high admission. Using a computer method, a demographic analysis of these four
      groups of census tracts was then carried out to examine the correlation between
      the density of admissions and various demographic characteristics. During the
      course of the study, various correlations between high admissions to the child
      and adolescent psychiatric inpatient clinic and various demographic
      characteristics emerged. Implications of these findings, in terms of present
      service and future planning, are discussed. 

PMID- 24310488
TI  - Adolescents' perceptions of the costs and benefits associated with cigarette
      smoking: Sex differences and peer influence.
AB  - This study explored the perceptions of young adolescents of the costs and
      benefits of cigarette smoking. These perceptions were examined as a function of
      the sex of the adolescent and peer smoking habits. The sample consisted of 155
      White middle class male and female adolescents, aged 12 to 15. The results
      indicate that endorsement of particular costs and benefits was related to the
      respondent's sex and whether or not the respondent had friends who smoked. The
      girls seemed to view smoking as a sign of rebellion or autonomy, while the boys
      seemed to view smoking cigarettes as a social coping mechanism. The effect of
      having friends who smoke was always mediated by the sex of the adolescents. Boys
      who have friends who smoke have attitudes that appear more conducive to smoking
      than do boys with nonsmoking friends. This relationship did not hold for girls.
      The implications for smoking education and intervention are discussed. 

PMID- 24310489
TI  - From family to peer: A review of transitions of influence among drug-using youth.
AB  - The research concerning relative and independent influences of family and peers
      upon adolescent drug use is reviewed. Although conflict between family and
      adolescents is one of the oldest, most predictable, and-in Western society
      probably least avoidable of developmental conflicts, the sharp focus upon this
      conflict in the context of adolescent drug use is a more recent development. As
      interest and concern regarding adolescent drug use has grown, so has the research
      seeking to explain this behavior. Much of this research has focused upon the role
      of family and peer influence. After a brief review of the theories which support
      either the greater impact of family or peer influence on adolescent behavior, a
      more specific review of the literature concerning the role of these influences on
      adolescent drug use is presented. The outline of this presentation is derived
      from Kandel's theory of stages of drug use. Finally, a summary of research
      findings and specific suggestions for future research are made. 

PMID- 24310490
TI  - Family factors associated with schizophrenia and anorexia nervosa.
AB  - This paper reports results of a longitudinal prospective study of 65 families
      first assessed when they presented at a psychological clinic with a disturbed
      adolescent offspring. Fifty-two of the index offspring were followed up five
      years later and assessed using Research Diagnostic Criteria (RDC). Parental
      attributes of communication deviance and negative affective style were associated
      with offspring who later manifested disorders of the extended schizophrenia
      spectrum. Comparison of this sample with anorectic and non-anorectic inpatient
      groups revealed unique patterns in the families of anorectics, which were
      different from those identified in the preschizophrenic cases. 

PMID- 24310491
TI  - Pituitary gland morphogenesis and ontogeny of adenohypophyseal cells of Salminus
      brasiliensis (Teleostei, Characiformes).
AB  - In this study, we describe for the first time the details of the pituitary gland
      morphogenesis and the ontogeny of adenohypophyseal cells of a South American
      Characiform species with great importance for Brazilian Aquaculture, Salminus
      brasiliensis (Characiformes, Characidae), from hatching to 25 days after hatching
      (dah), by histochemical and immunocytochemical methods. The pituitary placode was
      first detected at hatching (0 dah), and the pituitary anlage became more defined
      at 0.5 dah. The neurohypophysis (NH) development started at 3 dah, and the early
      formation of its stalk at 12.5 dah. An increase in adenohypophyseal and NH
      tissues was also observed, and in juveniles at 25 dah, the pituitary displayed
      similar morphology to that found in adults of this species, displaying the main
      features of the teleost pituitary. PRL cells were detected at 0.5 dah, together
      with ACTH and alpha-MSH cells, followed by GH and SL cells at 1.5 dah. beta-FSH
      cells were detected at 25 dah, while beta-LH cells at 5 dah. The pituitary
      development in this species comprises a dynamic process similar to other
      teleosts. Our findings in S. brasiliensis corroborate the heterogeneity in the
      ontogeny of adenohypophyseal cells in teleosts and suggest a role for
      adenohypophyseal hormones in the early development of this species. 

PMID- 24310492
TI  - Efficient Gene Silencing by Self-Assembled Complexes of siRNA and Symmetrical
      Fatty Acid Amides of Spermine.
AB  - Gene silencing by siRNA (synthetic dsRNA of 21-25 nucleotides) is a well
      established biological tool in gene expression studies and has a promising
      therapeutic potential for difficult-to-treat diseases. Five fatty acids of
      various chain length and oxidation state (C12:0, C18:0, C18:1, C18:2, C22:1) were
      conjugated to the naturally occurring polyamine, spermine, and evaluated for
      siRNA delivery and gene knock-down. siRNA delivery could not be related directly
      to gene silencing efficiency as N4,N9-dierucoyl spermine resulted in higher siRNA
      delivery compared to N4,N9-dioleoyl spermine. GFP silencing in HeLa cells showed
      that the unsaturated fatty acid amides are more efficient than saturated fatty
      acid amides, with N4,N9-dioleoyl spermine resulting in the most efficient gene
      silencing in the presence of serum. The alamarBlue cell viability assay showed
      that fatty acid amides of spermine have good viability (75%-85% compared to
      control) except N4,N9-dilauroyl spermine which resulted in low cell viability.
      These results prove that unsaturated fatty acid amides of spermine are efficient,
      non-toxic, non-viral vectors for siRNA mediated gene silencing. 

PMID- 24310493
TI  - Live cell in vitro and in vivo imaging applications: accelerating drug discovery.
AB  - Dynamic regulation of specific molecular processes and cellular phenotypes in
      live cell systems reveal unique insights into cell fate and drug pharmacology
      that are not gained from traditional fixed endpoint assays. Recent advances in
      microscopic imaging platform technology combined with the development of novel
      optical biosensors and sophisticated image analysis solutions have increased the
      scope of live cell imaging applications in drug discovery. We highlight recent
      literature examples where live cell imaging has uncovered novel insight into
      biological mechanism or drug mode-of-action. We survey distinct types of optical
      biosensors and associated analytical methods for monitoring molecular dynamics,
      in vitro and in vivo. We describe the recent expansion of live cell imaging into
      automated target validation and drug screening activities through the development
      of dedicated brightfield and fluorescence kinetic imaging platforms. We provide
      specific examples of how temporal profiling of phenotypic response signatures
      using such kinetic imaging platforms can increase the value of in vitro high
      content screening. Finally, we offer a prospective view of how further
      application and development of live cell imaging technology and reagents can
      accelerate preclinical lead optimization cycles and enhance the in vitro to in
      vivo translation of drug candidates. 

PMID- 24310494
TI  - Nanotechnology and drug delivery: an update in oncology.
AB  - The field of nanotechnology has exploded in recent years with diverse arrays of
      applications. Cancer therapeutics have recently seen benefit from nanotechnology
      with the approval of some early nanoscale drug delivery systems. A diversity of
      novel delivery systems are currently under investigation and an array of newly
      developed, customized particles have reached clinical application. Drug delivery
      systems have traditionally relied on passive targeting via increased vascular
      permeability of malignant tissue, known as the enhanced permeability and
      retention effect (EPR). More recently, there has been an increased use of active
      targeting by incorporating cell specific ligands such as monoclonal antibodies,
      lectins, and growth factor receptors. This customizable approach has raised the
      possibility of drug delivery systems capable of multiple, simultaneous functions,
      including applications in diagnostics, imaging, and therapy which is paving the
      way to improved early detection methods, more effective therapy, and better
      survivorship for cancer patients. 

PMID- 24310496
TI  - Semi-solid Sucrose Stearate-Based Emulsions as Dermal Drug Delivery Systems.
AB  - Mild non-ionic sucrose ester surfactants can be employed to produce lipid-based
      drug delivery systems for dermal application. Moreover, sucrose esters of
      intermediate lipophilicity such as sucrose stearate S-970 possess a peculiar
      rheological behavior which can be employed to create highly viscous semi-solid
      formulations without any further additives. Interestingly, it was possible to
      develop both viscous macroemulsions and fluid nanoemulsions with the same
      chemical composition merely by slight alteration of the production process.
      Optical light microscopy and cryo transmission electron microscopy (TEM) revealed
      that the sucrose ester led to the formation of an astonishing hydrophilic network
      at a concentration of only 5% w/w in the macroemulsion system. A small number of
      more finely structured aggregates composed of surplus surfactant were likewise
      detected in the nanoemulsions. These discoveries offer interesting possibilities
      to adapt the low viscosity of fluid O/W nanoemulsions for a more convenient
      application. Moreover, a simple and rapid production method for skin-friendly
      creamy O/W emulsions with excellent visual long-term stability is presented. It
      could be shown by franz-cell diffusion studies and in vitro tape stripping that
      the microviscosity within the semi-solid formulations was apparently not
      influenced by their increased macroviscosity: the release of three model drugs
      was not impaired by the complex network-like internal structure of the
      macroemulsions. These results indicate that the developed semi-solid emulsions
      with advantageous application properties are highly suitable for the unhindered
      delivery of lipophilic drugs despite their comparatively large particle size and
      high viscosity. 

PMID- 24310497
TI  - Influence of the vehicle on the penetration of particles into hair follicles.
AB  - Recently, it has been demonstrated that particulate substances penetrate
      preferentially into the hair follicles and that the penetration depth depends on
      the particle size. In the present study, the influence of the vehicle of the
      particulate substances on the penetration depth was investigated. Four different
      formulations (ethanolic suspension, aqueous suspension, ethanolic gel and aqueous
      gel) containing peptide-loaded particles of 1 um in diameter were prepared and
      applied on porcine ear skin. After penetration, punch biopsies were taken and the
      penetration depths of the particles were investigated by laser scanning
      microscopy. The deepest penetration was achieved with the gel formulations
      demonstrating an influence of the vehicle on the penetration depth of particulate
      substances. 

PMID- 24310495
TI  - Fluorescence molecular tomography: principles and potential for pharmaceutical
      research.
AB  - Fluorescence microscopic imaging is widely used in biomedical research to study
      molecular and cellular processes in cell culture or tissue samples. This is
      motivated by the high inherent sensitivity of fluorescence techniques, the
      spatial resolution that compares favorably with cellular dimensions, the
      stability of the fluorescent labels used and the sophisticated labeling
      strategies that have been developed for selectively labeling target molecules.
      More recently, two and three-dimensional optical imaging methods have also been
      applied to monitor biological processes in intact biological organisms such as
      animals or even humans. These whole body optical imaging approaches have to cope
      with the fact that biological tissue is a highly scattering and absorbing medium.
      As a consequence, light propagation in tissue is well described by a diffusion
      approximation and accurate reconstruction of spatial information is demanding.
      While in vivo optical imaging is a highly sensitive method, the signal is
      strongly surface weighted, i.e., the signal detected from the same light source
      will become weaker the deeper it is embedded in tissue, and strongly depends on
      the optical properties of the surrounding tissue. Derivation of quantitative
      information, therefore, requires tomographic techniques such as fluorescence
      molecular tomography (FMT), which maps the three-dimensional distribution of a
      fluorescent probe or protein concentration. The combination of FMT with a
      structural imaging method such as X-ray computed tomography (CT) or Magnetic
      Resonance Imaging (MRI) will allow mapping molecular information on a high
      definition anatomical reference and enable the use of prior information on
      tissue's optical properties to enhance both resolution and sensitivity. Today
      many of the fluorescent assays originally developed for studies in cellular
      systems have been successfully translated for experimental studies in animals.
      The opportunity of monitoring molecular processes non-invasively in the intact
      organism is highly attractive from a diagnostic point of view but even more so
      for the drug developer, who can use the techniques for proof-of-mechanism and
      proof-of-efficacy studies. This review shall elucidate the current status and
      potential of fluorescence tomography including recent advances in multimodality
      imaging approaches for preclinical and clinical drug development. 

PMID- 24310498
TI  - In vitro dissolution methods for hydrophilic and hydrophobic porous silicon
      microparticles.
AB  - Porous silicon (PSi) is an innovative inorganic material that has been recently
      developed for various drug delivery systems. For example, hydrophilic and
      hydrophobic PSi microparticles have been utilized to improve the dissolution rate
      of poorly soluble drugs and to sustain peptide delivery. Previously, the well
      plate method has been demonstrated to be a suitable in vitro dissolution method
      for hydrophilic PSi particles but it was not applicable to poorly wetting
      hydrophobic thermally hydrocarbonized PSi (THCPSi) particles. In this work, three
      different in vitro dissolution techniques, namely centrifuge, USP Apparatus 1
      (basket) and well-plate methods were compared by using hydrophilic thermally
      carbonized PSi (TCPSi) microparticles loaded with poorly soluble ibuprofen or
      freely soluble antipyrine. All the methods showed a fast and complete or nearly
      complete release of both model compounds from the TCPSi microparticles indicating
      that all methods described in vitro dissolution equally. Based on these results,
      the centrifuge method was chosen to study the release of a peptide (ghrelin
      antagonist) from the THCPSi microparticles since it requires small sample amounts
      and achieves good particle suspendability. Sustained peptide release from the
      THCPSi microparticles was observed, which is in agreement with an earlier in vivo
      study. In conclusion, the centrifuge method was demonstrated to be a suitable
      tool for the evaluation of drug release from hydrophobic THCPSi particles, and
      the sustained peptide release from THCPSi microparticles was detected. 

PMID- 24310499
TI  - Interactions of tenofovir, Lamivudine, abacavir and Didanosine in primary human
      cells.
AB  - Certain triple nucleoside/tide reverse transcriptase inhibitor (NRTI) regimens
      containing tenofovir (TDF) have been associated with rapid early treatment
      failure. The mechanism is unknown, but may be at the level of drug transport. We
      measured the lipophilicity of the drugs [3H]-lamivudine (3TC), -didanosine (ddI),
      -TDF and -ABC. Peripheral blood mononuclear cells (PBMCs) were used to evaluate
      drug-drug interactions at the level of drug transport. PBMCs were measured for
      the expression of P-glycoprotein (P-gp), multidrug resistance-associated protein
      1 (MRP-1) and breast cancer resistance protein (BCRP) by flow cytometry. The rank
      order of the lipophilicity of the drugs were ABC>>>3TC3ddI>TDF. The accumulation
      of [3H]-3TC, -ddI and -TDF were temperature sensitive (suggesting facilitated
      transport), in contrast to [3H]-ABC. ABC reduced the accumulation of [3H]-3TC,
      and cell fractionation experiments suggested this was mainly in membrane-bound
      [3H]-3TC. ABC/TDF and ABC/ddI increased the accumulation of [3H]-3TC and 3TC/TDF
      also increased the accumulation of [3H]-TDF. In contrast, none of the NRTI/NtRTI
      incubations (alone or in combination) altered the accumulation of [3H]-ABC and 
      ddI. PBMC expression of P-gp, MRP1 and BCRP were detected, but none correlated
      with the accumulation of the drugs. The high failure rates seen with TDF, ABC and
      3TC are not fully explained by an interaction at transporter level. 

PMID- 24310500
TI  - Detection and genotype analysis of human papillomavirus in non-small cell lung
      cancer patients.
AB  - Although the role of human papillomavirus (HPV) in the development of uterine
      cervical cancer is well established, the role of HPV in lung carcinogenesis
      remains controversial. The detection rates of HPV DNA are subject to a wide
      variation from 0 to 100%. This is partly influenced by the detection techniques
      employed. To elucidate the impact of HPV infection on lung parenchyma, we
      analyzed 100 non-small cell lung cancer (NSCLC) specimens (39 squamous cell
      carcinomas, 50 adenocarcinomas, 5 samples with characteristics of both squamous
      cell and adenocarcinoma, 5 undifferentiated and 1 large cell carcinoma) from the
      region of Crete, Greece. Sixteen non-cancerous samples served as the negative
      controls. DNA was extracted from 100 paraffin-embedded tissue sections obtained
      from NSCLC patients. The specimens were examined for the detection of HPV DNA by
      Real-Time PCR using GP5+/GP6+ primers. Furthermore, the HPV-positive samples were
      subjected to genotyping. In contrast to the absence of viral genomes in the
      control samples, HPV DNA was detected in 19 NSCLC specimens (19%). In particular,
      4 squamous cell carcinomas, 12 adenocarcinomas, 1 sample with characteristics of
      both squamous cell and adenocarcinoma, and 2 undifferentiated samples were HPV
      positive. The distribution of HPV genotypes was as follows: HPV 16: eight cases
      (42.1%); HPV 11: three cases (15.8%); HPV 6: one case (5.2%); HPV 59: one case
      (5.2%); HPV 33: two cases (10.5%); HPV 31: two cases (10.5%) and HPV 18: two
      cases (10.5%). The presence of HPV in the tumor samples provides evidence of the
      potential role of HPV in NSCLC and strongly argues for additional research on
      this issue.

PMID- 24310501
TI  - Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular
      carcinoma in vitro and in vivo.
AB  - Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the
      world whose chemoprevention became increasingly important in HCC treatment.
      Although the anticancer effects of asparagus constituents have been investigated
      in several cancers, its effects on hepatocellular carcinoma have not been fully
      studied. In this study, we investigated the anticancer effects of the
      deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells
      using the in vitro and in vivo experimental model. Our data showed that
      deproteinized asparagus polysaccharide might act as an effective inhibitor on
      cell growth in vitro and in vivo and exert potent selective cytotoxicity against
      human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that
      it could potently induce cell apoptosis and G2/M cell cycle arrest in the more
      sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus
      polysaccharide potentiated the effects of mitomycin both in vitro and in vivo.
      Mechanistic studies revealed that deproteinized asparagus polysaccharide might
      exert its activity through an apoptosis-associated pathway by modulating the
      expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus
      polysaccharide exhibited significant anticancer activity against hepatocellular
      carcinoma cells and could sensitize the tumoricidal effects of mitomycin,
      indicating that it is a potential therapeutic agent (or chemosensitizer) for
      liver cancer therapy. 

PMID- 24310502
TI  - The volume and duration of wound drainage are independent prognostic factors for
      breast cancer.
AB  - Drain insertion is routinely done after breast cancer surgery. However, the
      prognostic value of suction drains in breast cancer is still unknown. This study
      aimed to reveal the prognostic value of drain insertion in breast cancer. A total
      of 296 female breast cancer patients undergoing surgery were retrospectively
      recruited. The correlation of drainage volume as well as drain duration with
      clinicopathological parameters and prognosis was assessed statistically. We found
      that breast cancer patients with a drainage volume of >240 ml had a better
      overall survival time. Breast cancer patients with more than 5 days postoperative
      drain duration would have better survival time. In addition, both the volume and
      duration of wound drainage are independent prognostic factors in multivariate
      analysis. Therefore, the volume of drainage as well as drain duration is a
      potential novel prognostic marker for breast cancer.

PMID- 24310503
TI  - The association of APE1 Asp148Glu gene polymorphisms and lung cancer risk: an
      updated meta-analysis.
AB  - Many studies have examined the association between APE1 Asp148Glu (rs3136820)
      polymorphism gene polymorphisms and lung cancer risk in various populations, but
      their results have been inconsistent. To assess this relationship more precisely,
      a meta-analysis was performed. PubMed and CNKI databases were searched for case
      control studies published up to October 2013. Data were extracted, and pooled
      odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately,
      14 studies, comprising 4,165 lung cancer cases and 5,438 controls were included.
      Overall, for Glu carriers (Asp/Glu + Glu/Glu) versus wild-type homozygotes
      (Asp/Asp), the pooled OR was 1.05 (95% CI = 0.96-1.15 P = 0.000 for
      heterogeneity); for Glu/Glu versus Asp/Asp, the pooled OR was 1.07 (95% CI = 0.95
      1.21 P = 0.007 for heterogeneity). In the stratified analysis by ethnicity, the
      significantly risks were not found among Asians or Caucasians. This updated meta
      analysis suggests that the APE1 Asp148Glu polymorphisms are not associated with
      lung cancer risk among Asians or Caucasians.

PMID- 24310504
TI  - Association of the vascular endothelial growth factor (VEGF) gene single
      nucleotide polymorphisms with osteosarcoma susceptibility in a Chinese
      population.
AB  - Osteosarcoma (OS) is the most common bone malignancy worldwide. The vascular
      endothelial growth factor (VEGF) gene plays an important role in the pathogenesis
      of OS. The objective of this study aimed to detect the potential association
      between VEGF genetic polymorphisms and OS susceptibility in Chinese Han
      population. We recruited 330 OS patients and 342 cancer-free controls in this
      case-control study. Three single-nucleotide polymorphisms (SNPs) (-634 G > C,
      +936 C > T, and +1612 G > A) of the VEGF gene were investigated by using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method and confirmed by direct DNA sequencing. Among these SNPs, we found that
      the genotypes/alleles of +936 C > T were statistically associated with the
      increased risk of OS (TT versus (vs.) CC: OR = 2.70, 95% CI 1.34-5.45, chi(2) =
      8.2271, p = 0.0041; T vs. C: OR = 1.31, 95% CI 1.02-1.68, chi(2) = 4.3861, p =
      0.0362). The T allele and TT genotype of +936 C > T could be factors that
      increase the risk for susceptibility to OS. The results from this study suggest
      that VEGF genetic variants are potentially related to OS susceptibility in
      Chinese Han population and might be used as molecular markers for assessing OS
      susceptibility.

PMID- 24310505
TI  - Clinical significance of serum transforming growth factor-beta 1 (TGF-beta1)
      levels in patients with epithelial ovarian cancer.
AB  - Transforming growth factor-beta 1 (TGF-beta1) plays an important role in the
      pathogenesis of multiple malignancies, and its expression also strongly affects
      the outcomes of cancer patients. The objective of this study was to determine the
      clinical significance of the serum levels of TGF-beta1 in epithelial ovarian
      cancer (EOC) patients. A total of 50 patients with a pathologically confirmed
      diagnosis of EOC were enrolled into this study. Serum TGF-beta1 concentrations
      were determined by the solid-phase sandwich ELISA method. Thirty age- and sex
      matched healthy controls were included in the analysis. Median age of patients
      was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced
      disease (FIGO stage III-IV; 90%). There was no significant difference in baseline
      serum TGF-beta1 levels between EOC patients and the controls (p = 0.39). A trend
      to significant relationship was found between the serum levels of TGF-beta1 and
      stage of disease (p = 0.06). The elevated serum TGF-beta1 level was associated
      with metastatic disease. The other known clinical variables including histology,
      grade of histology, debulking surgery, and serum CA 125 levels were not found to
      be correlated with serum TGF-beta1 concentrations (p > 0.05). Only the
      chemotherapy-unresponsive patients had higher serum TGF-beta1 levels compared
      with responsive ones (p = 0.02). Serum TGF-beta1 concentration was found to have
      no prognostic role for both progression-free and overall survivals (p = 0.42 and
      p = 0.09, respectively). In conclusion, although the serum level of TGF-beta1 has
      no diagnostic and prognostic role, it is associated with sensitivity to standard
      chemotherapy in EOC patients.

PMID- 24310506
TI  - Muscle transfers in children and adults improve external rotation in cases of
      obstetrical brachial plexus paralysis: a comparative study.
AB  - PURPOSE: Latissimus dorsi and teres major transfers to the lateral side of the
      humerus with lengthening of the pectoralis major and subscapularis muscles for
      residual shoulder deformity were compared in children and skeletally mature
      patients. METHODS: Fifteen patients (nine children, six skeletally mature
      patients aged three to 30 years, follow-up one to 22 years) were treated for
      internal shoulder contracture after birth plexus lesions: C5-C6 (seven patients);
      C5-7 (five patients); C5-C8-T1 (three patients, respectively). Range of movement,
      Mallet shoulder function score and radiographs were assessed. RESULTS: Pre
      operatively, shoulder function restrictions were comparable in all patients.
      Postoperatively, external rotation, abduction and Mallet function score improved
      significantly (p < 0.05) in all patients except one. There were no differences in
      improvement between children and skeletally mature patients (p = 0.24-1.0).
      CONCLUSIONS: This technique improves external rotation and abduction of the
      shoulder for daily living activities in children and young, skeletally mature,
      patients.

PMID- 24310507
TI  - Management of displaced intra-articular calcaneal fractures using the limited
      open sinus tarsi approach and fixation by screws only technique.
AB  - PURPOSE: Evaluation of management of the displaced intra-articular calcaneal
      fractures (DIACF) Sanders types II and III by using minimally invasive sinus
      tarsi approach and fixation by screws only technique. METHODS: Open reduction
      using the limited lateral approach and internal fixation using screws only was
      studied in 33 patients with unilateral isolated simple DIACF with a mean age of
      35 years (15 type II patients and 18 type III patients). All patients were
      evaluated both clinically and radiologically. RESULTS: With a mean follow-up
      period of 28.8 months (range 12-53 months), no cases of failure of reduction or
      displacement of hardware were detected. The mean AOFAS was 91.73 points while the
      mean MFS was 95.09 points. Twenty-eight patients were able to resume their pre
      injury level of work while the remaining five refrained to sedentary jobs. The
      mean pre-operative Bohlers' angle was 2.8 degrees  (range from -38o to 24o) while
      postoperatively it was 19.4 degrees  (range 5o to 49o). There was no
      statistically significant difference when comparing the results (AOFAS p-value
      1.00, MFS p-value 0.81) between Sanders' type II and III fractures. One patient
      had postoperative superficial wound infection. Seven patients complained of
      prominent screw heads. Complex regional pain syndrome occurred in seven patients
      and was treated successfully at six months duration. CONCLUSION: The limited open
      sinus tarsi approach can be used successfully to treat displaced Sanders type II
      and III fractures. It allows for adequate visualization and reduction. Fixation
      by screws only is also sufficient. It also clearly avoids the major wound
      complication problems.

PMID- 24310509
TI  - Demand uncertainty and hospital costs: an application to Portuguese public
      hospitals.
AB  - In this paper, we evaluate the effect of demand uncertainty on hospital costs.
      Since hospital managers want to minimize the probability of not having enough
      capacity to satisfy demand, and since demand is uncertain, hospitals have to
      build excess capacity and incur the associated costs. Using panel data comprising
      information for 43 Portuguese public hospitals for the period 2007-2009, we
      estimate a translog cost function that relates total variable costs to the usual
      variables (outputs, the price of inputs, some of the hospitals' organizational
      characteristics) and an additional term measuring the excess capacity related to
      the uncertainty of demand. Demand uncertainty is measured as the difference
      between actual and projected demand for emergency services. Our results indicate
      that the cost function term associated with the uncertainty of demand is
      significant, which means that cost functions that do not include this type of
      term may be misspecified. For most of our sample, hospitals that face higher
      demand uncertainty have higher excess capacity and higher costs. Furthermore, we
      identify economies of scale in hospital costs, at least for smaller hospitals,
      suggesting that a policy of merging smaller hospitals would contribute to
      reducing hospital costs. 

PMID- 24310510
TI  - Cauliflower Mosaic Virus replication complexes: characterization of the
      associated enzymes and of the polarity of the DNA synthesized in vitro.
AB  - The synthesis of both strands of CaMV-DNA has been studied in vitro using viral
      replication complexes obtained by hypotonic extraction of infected plant
      organelles. Hybridization of the DNA synthesized in vitro to single stranded CaMV
      DNA probes cloned in bacteriophage M 13 confirmed that the 35 S RNA served as a
      template for the synthesis of the (-) DNA strand. The response of CaMV DNA
      synthesis to various inhibitors suggests that a single enzyme directs both steps
      of the replication cycle. A comparative activity gel analysis of the DNA
      polymerases present in nuclear extracts from healthy and CaMV-infected turnips
      revealed an increase of a DNA polymerase species migrating in the 75 Kd range in
      infected tissue. When the enzyme activity associated with the isolated
      replicative complexes was similarly analyzed, the 75 Kd polymerase was markedly
      predominant, confirming that DNA polymerases of the alpha-type (MW in the 110 Kd
      range) are not involved in the aphidicolin-insensitive CaMV DNA replication. It
      seems therefore increasingly probable that CaMV codes for its own polymerase. 

PMID- 24310511
TI  - Blue light control of the level of two plastid mRNAs in cultured plant cells.
AB  - In suspension cultured callus cells of tobacco (Nicotiana tabacum var. 'Samsun')
      the development of chloroplasts is strictly blue light-dependent. During this
      process chlorophylls and other pigments as well as membrane and stroma proteins
      are synthesized de-novo. Cloned chloroplast genes of mustard encoding the large
      subunit (LSU) of ribulosebisphosphate carboxylase/oxygenase (EC. 4.1.1.39;
      RuBPCase) and the precursor polypeptide of the 32-kD membrane protein were used
      to study the effect of blue light on the steady-state concentration of the
      complementary mRNA sequences. For both a rapid increase in dark-grown cells in
      response to blue light-irradiation was detected by RNA dot-hybridization
      technique. The time courses coincide with those previously elucidated for the
      synthesis rates of both LSU and the membrane protein. The results support the
      notion that blue light acts primarily through mRNA induction. 

PMID- 24310512
TI  - Synthesis of subunit III of CF0 by thylakoid-bound polysomes from pea
      chloroplasts.
AB  - Wahsed thylakoid membranes from pea chloroplasts incorporate label from ((35)S)
      methionine into protein when supplemented with S-30 soluble factors from E. coli.
      One of the products associated with the thylakoids is soluble in butanol,
      precipitated by ether and has an apparent molecular mss of 8200D on urea-lithium
      dodecyl sulphate (LDS) polyacrylamide gels. In addition, the protein covalently
      binds dicyclohexylcarbo-diimide (DCCD) which causes it to migrate as two slower
      forms on gels. Based on these criteria we establish that the proteolipid or
      subunit III of CF0 (the intrinsic sector of the ATPase complex) is synthesized by
      the thylakoid bound polysomes. 

PMID- 24310513
TI  - Tryptophan decarboxylase from Catharanthus roseus cell suspension cultures:
      purification, molecular and kinetic data of the homogenous protein.
AB  - The purification of tryptophan decarboxylase from Catharanthus roseus (TDC,
      E.C.:4.1.1.27), to apparent homogeneity, is described. The enzyme represents a
      soluble protein with a molecular weight of 115 000+/-3 000, consisting of 2
      identical subunits of 54 000+/-1 000. The pI was estimated to be 5.9 and the Km
      for L-tryptophan was found to be 7.5*10(-5) M. Phenylalanine, tyrosine and DOPA
      were not decarboxylated by tryptophan decarboxylase from Catharanthus cells.
      Similar to the aromatic amino acid decarboxylase from hog kidney the enzyme does
      not appear to be obligatorily dependent on exogenously supplied pyridoxal
      phosphate, as it seems to contain a certain amount of this cofactor. The average
      percentage of TDC in the cells was found to be 0.002% in the growth medium while
      the level increased up to 0.03% when indole alkaloid biosynthesis was induced.
      The role of the protein as a bottleneck enzyme of indole alkaloid biosynthesis is
      discussed. 

PMID- 24310514
TI  - Progress in cellular engineering of plants: biochemical and genetic assessment of
      selectable markers from cultured cells.
AB  - Recent availability of stable and well characterized selectable markers and
      ability to combine alien genomes parasexually have contributed to the development
      of molecular biology in higher plants, including gene expression and genetic
      manipulation.Several types of biochemical mutants (resistant to inhibitory
      concentrations of aminoacid(s) or aminoacid analogs as well as deficient for
      enzyme activity) have recently been isolated and characterized biochemically and
      genetically. Among them, mutants with alterations in the nitrogen and aminoacid
      metabolism, or in the activity of alcohol dehydrogenases are being used in the
      development of more efficient techniques of gene transfer.The manipulation of
      whole genomes by sexual or somatic cell fusion offers new potential in this
      field, but refinement of transfer techniques is desirable. The new set of
      selectable markers obtained through advanced cellular technology, as well as our
      ability to regenerate plants from manipulated cell lines are expected to play a
      major role in cellular engineering. 

PMID- 24310515
TI  - Isolation of methotrexate-resistant cell lines in Petunia hybrida upon stepwise
      selection procedure.
AB  - Cell suspensions of Petunia hybrida were subjected to a selection procedure in
      which the concentration of the selective agent, methotrexate (MTX), was gradually
      elevated. In mammalian cells, this procedure frequently results in MTX-resistant
      mutants due to amplification of the gene coding for dihydrofolate reductase
      (DHFR), the target protein of MTX.Five suspension lines were isolated, with
      degrees of resistance ranging from 10 to 500 MUM MTX (in wild type the LD99.9 is
      0.2 MUM). MTX(R) phenotypes were unstable, as manifested by the loss of
      resistance upon prolonged growth in the absence of drug. All of the mutants also
      exhibited high values of MTX-binding protein (60- to 400-fold higher than that of
      the wild type), which declined to intermediate values upon MTX withdrawal.
      Finally, cellular extracts from all of the mutants also showed high specific
      staining of DHFR-activity in gels.The results suggest that the resistance of MTX
      in these plant cell-lines is mediated by the elevation of the amounts of DHFR,
      probably as a consequence of gene amplification. 

PMID- 24310517
TI  - Plant biotechnology news & views.

PMID- 24310516
TI  - Organization and nucleotide sequence of the genes for spinach chloroplast
      tRNA(Glu) and tRNA (Tyr.).
AB  - The map location and nucleotide sequence of the genes and flanking regions for
      tRNAUUC (Glu) (trnE) and tRNAGUA (Tyr) (trnY) from spinach (Spinacia oleracea)
      chloroplast DNA have been determined. The genes lie approximately midway between
      the genes for tRNAGGU (Thr) (trnT) and tRNAGUC (Asp) (trnD) on BamH1 fragment 8b,
      the arrangement being trnT, 458 bp, trnE, 64 bp, trnY, 409 bp, trnD. trnE and
      trnY are encoded by the same DNA strand as trnD and the direction of their
      transcription is divergent with respect to the transcription of trnT. trnE and
      trnY are 89% and 74% homologous, respectively, with the corresponding Euglena
      gracilis chloroplast genes. The corresponding homologies between the spinach
      chloroplast and E. coli genes are 72% and 61%. trnE is unusual in that it has the
      sequence 5'ATTCNA rather than 5'GTTCNA in the TPsi arm. Northern hybridizations
      to chloroplast RNA with restriction fragments carrying trnE and trnY sequences
      indicated that both genes are transcribed in vivo. 

PMID- 24310518
TI  - Increasing similarity in the dynamics of influenza in two adjacent subtropical
      Chinese cities following the relaxation of border restrictions.
AB  - The drivers of influenza seasonality remain heavily debated, especially in
      tropical/subtropical regions where influenza activity can peak in winter, during
      the rainy season, or remain constant throughout the year. We compared the
      epidemiological and evolutionary patterns of seasonal influenza epidemics in Hong
      Kong and Shenzhen, two adjacent cities in subtropical southern China. This
      comparison represents a unique natural experiment, as connectivity between these
      two cities has increased over the past decade. We found that, whilst summer
      influenza epidemics in Shenzhen used to peak 1-3 months later than those in Hong
      Kong, the difference decreased after 2005 (P<0.0001). Phylogenetic analysis
      revealed that influenza isolates from Shenzhen have become genetically closer to
      those circulating in Hong Kong over time (P = 0.045). Furthermore, although
      Shenzhen isolates used to be more distant from the global putative source of
      influenza viruses than isolates from Hong Kong (P<0.001), this difference has
      narrowed (P = 0.02). Overall, our study reveals that influenza activities show
      remarkably distinct epidemiological and evolutionary patterns in adjacent
      subtropical cities and suggests that human mobility patterns can play a major
      role in influenza dynamics in the subtropics.

PMID- 24310520
TI  - Linking left ventricular function and mural architecture: what does the clinician
      need to know?

PMID- 24310519
TI  - Clinical and prognostic value of stress echocardiography appropriateness criteria
      for evaluation of coronary artery disease in a tertiary referral centre.
AB  - OBJECTIVE: Appropriateness criteria for stress echocardiography (SE) have been
      published to reduce the rate of inappropriate testing. We sought to investigate
      the clinical impact and prognostic value of these criteria. METHODS: 250
      consecutive patients undergoing SE for evaluation of coronary artery disease were
      classified into appropriate, uncertain and inappropriate categories according to
      appropriateness criteria. A positive SE was defined as the development of new
      wall motion abnormalities or a biphasic response. The primary end point was the
      composite of myocardial infarction and death. RESULTS: Of the 250 SE, 120 (48%)
      were dobutamine studies and 130 (52%) were exercise studies. 156 (62.4%), 71
      (28.4%) and 23 (9.2%) were classified as appropriate, inappropriate and
      uncertain, respectively. A significantly greater proportion of studies classified
      as appropriate 71 (45.5%) demonstrated inducible ischaemia compared with
      inappropriate studies 9 (12.7%) or uncertain studies 4 (17.4%), p<0.0001. During
      a median follow-up of 12.4 months, events occurred in 18 (11.5%), 2 (2.8%) and 0
      patients classified as appropriate, inappropriate and uncertain, respectively.
      Event-free survival was significantly reduced in patients with a SE demonstrating
      ischaemia compared with patients without inducible ischaemia, p<0.0001. Kaplan
      Meier curves demonstrated reduced event-free survival in patients with whose
      studies were classified as appropriate compared to inappropriate (p=0.01) or
      uncertain (p=0.05). CONCLUSIONS: Appropriateness criteria differentiate between
      patients at high risk of ischaemia, subsequent revascularisation/cardiac events
      (appropriate group) and those at low risk of events (inappropriate group). A
      large proportion of SE is currently performed in inappropriate patients.
      Implementation of the criteria in clinical practice would reduce unnecessary
      testing.

PMID- 24310521
TI  - The impact of the coronary collateral circulation on outcomes in patients with
      acute coronary syndromes: results from the ACUITY trial.
AB  - OBJECTIVE: We sought to assess the prognostic role of collaterals in a large
      population of patients presenting with an acute coronary syndrome (ACS). METHODS:
      The coronary collateral circulation was assessed by an independent angiographic
      core laboratory using the Rentrop Score in patients enrolled in the randomised
      Acute Catheterization and Urgent Intervention Triage Strategy trial. RESULTS: The
      cohort comprised 5412 patients with moderate to high risk ACS. A total of 858
      patients (16.0%) had visible collaterals while 4554 patients (84.0%) had no
      collaterals. After multivariable adjustment, there were no differences in
      clinical outcomes at 1 year between the groups, including major adverse cardiac
      events (MACE) (HR 0.94 (95% CI 0.76 to 1.16), p=0.55), mortality (HR 1.03 (0.65
      to 1.62), p=0.91), myocardial infarction (MI) (HR 1.07 (0.83 to 1.38), p=0.60)
      and unplanned target vessel revascularisation (TVR) (HR 0.95 (0.71 to 1.28),
      p=0.75). Similarly, in the subgroup of patients undergoing percutaneous coronary
      intervention (PCI), the adjusted HR for major adverse cardiac events was 1.1
      (0.76 to 1.61), p=0.595; 0.81 (0.10 to 6.44), p=0.999 for mortality; and 0.86
      (0.54 to 1.35), p=0.564 for MI. The risk of unplanned TVR was increased (HR 2.74
      (1.48 to 5.10), p=0.004). CONCLUSIONS: In contrast to other studies, this large
      core laboratory-based analysis does not confirm a beneficial role of visible
      coronary collateral vessels on clinical outcomes in patients with ACS; the
      presence of collaterals was even associated with increased mortality in the
      unadjusted analysis. Collaterals were associated with a higher risk of TVR in
      patients undergoing PCI, a finding that may not have been fully corrected given
      confounders and clinical differences between the groups. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT00093158.

PMID- 24310522
TI  - Isolation and characterization of soil Streptomyces species as potential
      biological control agents against fungal plant pathogens.
AB  - The use of antagonist microorganisms against fungal plant pathogens is an
      attractive and ecologically alternative to the use of chemical pesticides.
      Streptomyces are beneficial soil bacteria and potential candidates for biocontrol
      agents. This study reports the isolation, characterization and antagonist
      activity of soil streptomycetes from the Los Petenes Biosphere Reserve, a Natural
      protected area in Campeche, Mexico. The results showed morphological,
      physiological and biochemical characterization of six actinomycetes and their
      inhibitory activity against Curvularia sp., Aspergillus niger, Helminthosporium
      sp. and Fusarium sp. One isolate, identified as Streptomyces sp. CACIS-1.16CA
      showed the potential to inhibit additional pathogens as Alternaria sp.,
      Phytophthora capsici, Colletotrichum sp. and Rhizoctonia sp. with percentages
      ranging from 47 to 90 %. This study identified a streptomycete strain with a
      broad antagonist activity that could be used for biocontrol of plant pathogenic
      fungi. 

PMID- 24310523
TI  - Total antioxidant capacity and oxidative stress after a 10-week dietary
      intervention program in obese children.
AB  - Dietary and serum total antioxidant capacity (TAC) are considered appropriate
      tools for investigating the potential health effects of dietary antioxidants
      consumed in mixed diets. The aim was to analyze the impact of a dietary
      intervention on macronutrient intakes and to evaluate the improvement on
      oxidative status after weight loss (WL) by measuring dietary and serum TAC, and
      urinary F2-isoprostane levels as markers of oxidative stress. Forty-four
      overweight/obese children (mean age 11.5 years) were enrolled to undergo a 10
      week WL program. They were dichotomized at the median of body mass index-standard
      deviation score (BMI-SDS) change, as high (HR) and low responders (LR) after
      intervention. Subjects were prescribed with a fixed full-day meal diet,
      calculated according to their basal metabolic rate and physical activity levels.
      A validated food-frequency questionnaire was used to retrospectively calculate
      TAC and daily nutrient intake. The HR subjects were able to reduce anthropometric
      indices and to improve lipid and glucose profile. They also significantly
      diminished fat intake (p = 0.013). Moreover, baseline serum TAC values did
      significantly predict the reduction in urinary F2 isoprostane (B = -0.236 (-0.393
      to -0.078); p = 0.014) in the HR group after the WL program. Notably, changes in
      dietary TAC after the treatment were associated with a decrease in body weight
      after the 10-week intervention (B = -2.815 (-5.313 to -0.318), p = 0.029) in the
      HR group. The -DeltaSerumTAC/DeltaDietaryTAC and the 
      DeltaF2Isoprostane/DeltaDietaryTAC ratios revealed that the relationships between
      oxidative markers and antioxidants dietary intake were more favorable in the HR
      than in the LR group. CONCLUSION: Our study showed that a 10-week WL program was
      able to reduce adiposity indices in obese children. Moreover, after the
      intervention changes in dietary TAC and WL were significantly associated. Our
      result suggests that specific food with a high TAC content (such as fruits,
      vegetables, and legumes) could be recommended to improve WL.

PMID- 24310524
TI  - Risk factors for relapse and surgery rate in children with Crohn's disease.
AB  - The aim of this study was to evaluate risk factors associated with the relapse
      rate in the first year and the need for surgery in children with Crohn's disease
      (CD). Data of all children (n = 74) diagnosed with CD from January 2004 to June
      2011 were retrospectively analyzed. Multivariate Cox proportional hazards
      regression model was used to assess whether important clinical variables at
      diagnosis (age, presence of perianal disease, first induction therapy, first
      maintenance therapy, levels of Pediatric CD Activity Index (PCDAI), C-reactive
      protein (CRP), and standard deviation score (SDS) for height for weight) were
      associated with the risk of clinical recurrence in the first year and need for
      surgery during follow-up. Relapse occurred in 36 (48.6 %) patients in the first
      year from diagnosis. The only significant parameter associated with negative risk
      of relapse in the first year was exclusive enteral nutrition (EEN) used as
      induction therapy (hazard ratio (HR) 0.469, 95 % confidence interval (CI) 0.232
      0.948). EEN induced remission in 84.2 % of patients. The only risk associated
      with EEN treatment failure was the involvement of the upper gastrointestinal
      tract. During the follow-up, 25 (33.7 %) patients underwent surgery. The
      multivariate Cox regression model failed to recognize significant risk factor for
      surgery. CONCLUSION: This study underlines the importance of early EEN in the
      treatment of CD; it is not only efficacious in the remission induction but could
      also prevent relapse in the first year.

PMID- 24310525
TI  - Prevalence of self-reported nonmedical use of prescription stimulants in North
      Carolina Doctor of Pharmacy students.
AB  - OBJECTIVES: To evaluate the prevalence, associated factors, and opinions
      regarding nonmedical use of prescription stimulants (NMUPS) in Doctor of Pharmacy
      (PharmD) students. METHODS: An electronic survey was distributed to professional
      year 1 through 4 for students at 2 schools of pharmacy (public and private) in
      North Carolina. The survey was available for 3 weeks. Descriptive statistics
      (proportion of responders plus 95% confidence intervals [CIs]) were used to
      describe the primary objective. RESULTS: Of the 1043 surveys distributed, 407
      were completed giving a 39% response rate. The results indicated that 9% (95% CI:
      6.44-11.93) of PharmD students acknowledge NMUPS at least once during their
      pharmacy education. Additionally, 3% (95% CI: 1.90-5.45) acknowledge NMUPS at
      least once during the current pharmacy school year (past 5 months). Nonmedical
      prescription stimulant users were 9 times more likely to participate in NMUPS
      prior to pharmacy school (P < .0001) and 4.5 times more likely to use other
      illicit substances (P = .0076). CONCLUSION: The study identified the PharmD
      student population as high risk of abuse of prescription drug stimulants, which
      requires further research and attention. Additionally, there was a clear upward
      trend in the prevalence of NMUPS, and this misuse was associated with other
      detrimental behaviors.

PMID- 24310526
TI  - Abnormal tissue proliferation and life span variability in chronically irradiated
      dogs.
AB  - Data extracted from the gamma Beagle Dog Tissue Archive hosted by the Woloschak
      Laboratory (Chicago, IL, USA) were used in a retrospective comparative study of
      the influence of associated morbidities on the ability of organisms to regenerate
      hematopoietic cells. There were 209 dogs that had been subjected to whole-body
      irradiation from a cobalt 60 source from 1.1 years of age until death, with dose
      rates of 0.003-0.038 Gy/day. One hundred fifty-six nonirradiated dogs served as
      controls. The presence of neoplasms clinically recorded during each dog's
      lifetime (uncertain benign or malignant nature) was used to assign experimental
      subjects and controls to one of two groups: W (with) and WO (without) lesions.
      Differences between the two groups were noted, mainly a longer average life span
      and a prevalence of solid malignancy over malignant hematopoiesis in both
      irradiated and nonirradiated W dogs. We propose an interpretation of these data
      as showing variability of the activity of tissue-committed hematopoietic stem
      cells, reflected not only by an increased incidence of solid benign and malignant
      tumors, but also by greater marrow radioresistance and a stronger viability of W
      cohorts.

PMID- 24310527
TI  - Boron-pyridyl-imino-isoindoline dyes: facile synthesis and photophysical
      properties.
AB  - The synthesis of boron-pyridyl-imino-isoindoline dyes, a novel type of BODIPY
      analogue, involves a facile and scalable two-step reaction. Broad envelopes of
      intense vibrational bands are observed for the main spectral bands in the
      absorption and emission spectra. High fluorescence quantum yields are obtained in
      solution, with significant intensity also observed in the solid-state. 

PMID- 24310528
TI  - Associations of work activities requiring pinch or hand grip or exposure to hand
      arm vibration with finger and wrist osteoarthritis: a meta-analysis.
AB  - OBJECTIVE: We systematically reviewed the epidemiologic evidence linking finger
      and wrist osteoarthritis (OA) with work activities requiring pinch or hand grip
      or exposure to hand-arm vibration (HAV). METHODS: PubMed and Embase databases
      were searched up to June 2013. We selected studies assessing the associations of
      radiographic diagnosed finger and/or wrist joint OA with work activities
      involving pinch or hand grip or exposure to HAV. We used specific criteria to
      evaluate completeness of reporting, potential confounding, and bias. Pooled odds
      ratios (OR) were computed using random-effects meta-analyses. RESULTS: Of the 19
      studies included, 17 were cross-sectional, 1 was a prospective cohort, and 1 a
      case-control study. The meta-analyses of studies that controlled their estimates
      for at least age and gender showed the associations of pinch grip work with
      proximal interphalangeal joint [OR 1.56, 95% confidence interval (95% CI) 1.09
      2.23] and the first carpometacarpal joint OA (OR 2.10, 95% CI 1.06-4.17), but not
      with distal interphalangeal, metacarpalphalangeal, or wrist joints OA. Hand grip
      work and exposure to HAV were not associated with any finger or wrist OA.
      CONCLUSION: Epidemiological studies provide limited evidence that pinch grip may
      increase the risk of wrist or finger OA, but causal relation cannot be resolved
      because of cross-sectional designs and inadequate characterization of
      biomechanical strain to the hand and wrist.

PMID- 24310536
TI  - Self-esteem and delinquency revisited.
AB  - A recent investigation by Rosenberg and Rosenberg used longitudinal data from the
      Youth in Transition study to explore the causal relationships between delinquency
      and self-esteem. The present study is based on the same sample of young men in
      high school and extends Rosenberg and Rosenberg's analysis, first by using the
      same cross-lagged correlation methods applied over a longer time period, and then
      by employing a "causal modeling" approach using the LISREL computer program. Each
      of the analyses was carried out using the total sample as well as two subsamples,
      the highest and lowest quartiles in initial self-esteem. The causal modeling
      analyses attempted (a) to take careful account of the actual periods referenced
      by the measures of delinquency and self-esteem, (b) to control socioeconomic
      status and ability, and (c) to extend the model to demonstrate ways in which
      participation in teenage social life and current educational attainment might
      also influence and be influenced by self-esteem. The analyses suggest that self
      esteem plays little part in influencing the teenage behaviors and orientations
      that follow in time. Consistent with Kaplan's prediction, among young men who
      enter high school with low self-esteem, the effects of delinquent behavior tend
      primarily to be self-enhancing. 

PMID- 24310537
TI  - Imaginary audience behavior and perceptions of parents among delinquent and
      nondelinquent adolescents.
AB  - Imaginary audience behavior and perceptions of parents among a group of male
      delinquents and nondelinquent male and female adolescents were assessed. Each
      subject was administered the Imaginary Audience Scale and an author-designed
      inventory which measured perceived parental support. The results showed that the
      delinquents, compared to the nondelinquent males, expressed greater concern about
      the imaginary audience and had more negative perceptions of their fathers.
      Stronger concerns about the imaginary audience were positively correlated and
      negatively correlated with perceptions of low parental support among the
      delinquents and the male nondelinquents, respectively. The male nondelinquents
      also expressed greater concern than the female nondelinquents for the imaginary
      audience. Implications relating imaginary audience behavior and family relations
      to adolescent development are discussed. 

PMID- 24310538
TI  - Anorexia nervosa in the context of daily experience.
AB  - This research employed the Experience Sampling Method to study the daily lives of
      two anorectic women. They and 24 women from a normative population filled out
      reports on their experience at random moments during an ordinary week in their
      lives. The sample of 40-to-45 reports per person suggests that the anorectics
      spent more of their time alone and experienced lower average affect than other
      young single women. In addition, the reports from Case 1 provide concrete
      quantitative demonstration of an abnormal preoccupation with food. The reports
      from Case 2 show how this woman's moods are strongly tied to her fluctuating
      sense of control. 

PMID- 24310539
TI  - Biological and ecological factors in the expression of adolescent self-esteem.
AB  - The relationship between self-esteem and pubertal maturation is examined based on
      results of the first two years of a six-year naturalistic longitudinal study of
      the ecology of self-esteem during adolescence. A random sample of 40 seventh
      grade adolescents of both sexes from all socioeconomic classes was selected from
      a local junior high school. Four measures of pubertal maturation level were
      obtained for participants during each year of the study. Self-esteem was assessed
      by means of a repeated measures self-report technique. Each adolescent carried a
      "beeper" paging device and responded in writing to "beeps" that occurred on a
      random schedule eight times daily. Males were significantly higher in self-esteem
      than females. The developmental pattern for the relationship between self-esteem
      and pubertal maturation differed between boys and girls. Three ecological
      contextual variables were explored: setting, activity, and participants. Physical
      setting was significantly associated with level of self-esteem. Activities and
      participants present were not significantly predictive of self-esteem. Results
      are discussed in terms of the onset and timing of pubertal maturation and its
      influence on self-esteem. 

PMID- 24310540
TI  - The social, behavioral, and health effects of phencyclidine (PCP) use.
AB  - This study examined the perceived social, behavioral, and health effects of
      phencyclidine (PCP) use among a sample of 200 users in northern California. The
      study population, generated through snowball sampling techniques, included heavy
      chronic, light chronic, and recreational users; the vast majority of subjects
      were not in treatment facilities. Subjects reported that PCP use-particularly
      long-term, extensive use-resulted in frequent disruption of education and
      employment, impairment of relationships with parents and with lovers or spouses,
      involvement with the criminal justice system, and deterioration of physical and
      mental health. These findings provide systematic documentation of the extent to
      which problems previously associated with PCP use occurred among this population
      of users. In addition, the results illustrate the importance of examining the
      effects of PCP use in light of the psychosocial developmental processes of
      adolescence and early adulthood. 

PMID- 24310541
TI  - Self-image in adolescents with delayed puberty and growth retardation.
AB  - Fifty-six adolescents with varying combinations of pubertal delay and growth
      retardation were given the Offer Self-Image Questionnaire. Delay in sexual
      maturation by itself had no significant deleterious effect on self-image;
      however, growth retardation did. These results have important implications in
      determining indications for the endocrinological treatment of pubertal disorders.

PMID- 24310542
TI  - Keeping the faith: Psychosocial correlates of activism persistence into middle
      adulthood.
AB  - This study was conducted to determine certain ideological, personological,
      lifestyle, and familial correlates of activism persistence into middle adulthood.
      Almost 15 years following their arrest for participation in the Free Speech
      Movement, 30 former Berkeley activists responded to a political activity scale
      and measures selected to tap variables in each of the contextual domains.
      Although persisters did not differ from nonpersisters with respect to most
      lifestyle dimensions, they were distinguished by more radical beliefs, stronger
      repudiation of Protestant ethic values, and a stronger family legacy of social
      concern. The results provide more support for theories of activists' adult
      development based on notions of generational continuity, rather than generational
      rebellion. 

PMID- 24310543
TI  - From trust on intimacy: A new inventory for examining erikson's stages of
      psychosocial development.
AB  - A new inventory for examining the first six of Erikson's psychosocial stages is
      described. The self-report questionnaire, developed in a pilot study of 97
      adolescents and tested in a study of 622 adolescents, has 12 items for each
      subscale. Measures of reliability and validity are reported. It is concluded that
      the Erikson Psychosocial Stage Inventory (EPSI) is a useful measure for
      researchers interested in development from early adolescence and in mapping
      changes as a function of life events. 

PMID- 24310544
TI  - Chloride ion impact on materials for light-emitting electrochemical cells.
AB  - Small quantities of Cl(-) ions result in dramatic reductions in the performance
      of ionic transition metal complexes in light-emitting electrochemical cells.
      Strong ion-pairing between aromatic protons and chloride has been established in
      both the solid state and solution. X-ray structural determination of
      2{[Ir(ppy)2(bpy)][Cl]}.2CH2Cl2.[H3O].Cl reveals the unusual nature of an impurity
      encountered in the preparation of [Ir(ppy)2(bpy)][PF6]. 

PMID- 24310545
TI  - Individual profiles of free ceramide species and the constituent ceramide species
      of sphingomyelin and neutral glycosphingolipid and their alteration according to
      the sequential changes of environmental oxygen content in human colorectal cancer
      Caco-2 cells.
AB  - We previously performed a systematic analysis of free ceramide (Cers) species,
      the constituent ceramide species of sphingomyelins and neutral glycosphingolipids
      (NGSLs) using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry with high-energy collision-induced dissociation. As a result,
      distinct species differences were found among Cers, sphingomyelins and NGSLs in
      the kidneys. Using this method, we investigated various sphingolipid species from
      human colon cancer Caco-2 cells as well as the influence of environmental oxygen
      on these species in detail. Unexpectedly, even in normoxia, all Cers species were
      composed of dihydrosphingosine (d18:0) and non-hydroxy fatty acid (NFA), and 34%
      of sphingomyelins were composed of dihydrosphingomyelins with NFA. In contrast,
      major constituent ceramide species of NGSLs were composed of the usual long-chain
      base of sphingosine (d18:1) and hydroxy fatty acid (HFA). When the cells were
      cultured under hypoxic condition for 3 days, all the Cers and nearly 80% of the
      sphingomyelins were dihydrosphingolipids composed of d18:0-NFAs, but a
      significant proportion of d18:1-HFAs still remained in the NGSLs. When the cells
      were transferred from conditions of hypoxia to normoxia again (reoxygenation),
      Cer species composed of d18:1-NFAs, which were not found in Cers under the
      original normoxic conditions, appeared. Such Cers were probably synthesized as
      precursors for the constituent ceramides of sphingomyelins and NGSLs.

PMID- 24310546
TI  - The cross-modal double flash illusion depends on featural similarity between
      cross-modal inducers.
AB  - Despite extensive evidence of the possible interactions between multisensory
      signals, it remains unclear at what level of sensory processing these
      interactions take place. When two identical auditory beeps (inducers) are
      presented in quick succession accompanied by a single visual flash, observers
      often report seeing two visual flashes, rather than the physical one - the double
      flash illusion. This compelling illusion has often been considered to reflect
      direct interactions between neural activations in different primary sensory
      cortices. Against this simple account, here we show that by simply changing the
      inducer signals between featurally distinct signals (e.g. high- and low-pitch
      beeps) the illusory double flash is abolished. This result suggests that a
      critical component underlying the illusion is perceptual grouping of the inducer
      signals, consistent with the notion that multisensory combination is preceded by
      determination of whether the relevant signals share a common source of origin. 

PMID- 24310547
TI  - [Symptom assessment and management of pregnancy-related nausea and vomiting].
AB  - Pregnancy-related nausea and vomiting are uncomfortable symptoms. These symptoms
      are consistent across cultures, may persist for extended periods of time during
      the early stage of pregnancy, and may adversely affect expectant mothers and
      their fetuses. Further, these symptoms may negatively impact mother and infant
      health and increase medical costs in the absence of effective diagnosis and
      symptom management. Relevant literature and research is integrated to propose
      subjective and objective approaches to assessing symptoms such as a index of
      nausea, vomiting and retching (INVR) and to develop a preliminary clinical
      management model that prioritizes using a non-pharmacological strategy to treat
      mild and moderate nausea and vomiting. Article recommendations provide a
      practical clinical care reference to help pregnant women successfully pass
      through this uncomfortable stage and achieve better quality-of-life and birth
      outcomes. 

PMID- 24310548
TI  - [Miserable labor pain? Myths and nursing care].
AB  - Pain is a common, normal, and healthy physical phenomenon during childbirth.
      However, widely held public and clinical perspectives treat pain as a pathologic
      process and consider labor pain in a negative context. These perspectives ignore
      the positive effects of pain in the domains of protection, new life, expectation,
      purpose, preparation, and progression. The pain interpretation and pain
      experience of new mothers deeply impact their mental health, maternal-infant
      relationship, and transition to motherhood. This paper introduces the common
      myths related to labor pain, the three stages of pain transmission, and the
      current approaches to pain management. The authors hope childbirth caregivers may
      accept labor pain as a meaningful, pleasant, and positive gift, which is the
      first and most important step toward effective pain management. 

PMID- 24310549
TI  - [Childbirth-related fatigue during labor: an important but overlooked symptom].
AB  - Fatigue is not only a distressful symptom that is prevalent during labor; it may
      also interfere with the ability of laboring women to adjust to pain and bear down
      in the second labor stage as well as hinder maternal recovery and impair
      postpartum maternal-role performance. Childbirth-related fatigue is a frequent
      cause of physical and mental discomfort during labor and increases the likelihood
      of medical interventions such as instrumental delivery and cesarean section. Even
      so, as this fatigue is widely regarded as an inevitable part of the labor
      experience, little attention has been given to mediative interventions. In light
      of the above, this paper illustrates the definition and characteristics of
      childbirth-related fatigue during labor, analyzes the factors that affect this
      fatigue, and summarizes relevant nursing-care principles. It is hoped this paper
      increases nurse awareness of childbirth-related fatigue during labor and helps
      nurses take appropriate early prevention and intervention measures to reduce the
      adverse effects of fatigue and improve intrapartum care quality. 

PMID- 24310550
TI  - [Postpartum depression].
AB  - Postpartum psychological health is an important issue in postpartum care. This
      article introduces postpartum depression and describes its assessment, treatment,
      and nursing care. Postpartum depression is a non-psychotic depression that often
      commences 4 to 6 weeks after childbirth. Postpartum depression requires the
      diagnosis of at least 5 depressive symptoms that last for a period of at least 2
      weeks. Postpartum depression may occur within the first-year postpartum and, if
      not treated in a timely and appropriate manner, may adversely affect the health
      of the new mother, the child, and the family. Health professionals in regular
      contact with women during the perinatal period are encouraged to screen at-risk
      patients for postpartum depression and to assist postpartum-depressed patients
      adhere to prescribed treatment regimens to promote the health of the new family. 

PMID- 24310551
TI  - [Breast- and bottle-feeding in preterm infants: a comparison of behavioral cues].
AB  - BACKGROUND: Developmental care has been broadly applied to identify the
      behavioral cues and care needs of preterm infants. Past studies indicate a
      significantly higher level of physical distress in bottle-fed preterm infants
      than in preterm infants who are breastfed. However, no evidence has yet been
      reported that supports the influence of feeding methods on behavioral cues.
      PURPOSE: This study compares differences in the type and frequency of behavioral
      cues between breast- and bottle-fed preterm infants. METHODS: A comparison study
      design and secondary data analysis method were used to assess data from two
      previous research projects. Infant feeding behavioral cues were observed and
      compared between two groups: 7 preterm infants who were breastfed and 7 preterm
      infants who were bottle-fed. After cases were matched by infant gestational age,
      behavioral responses were coded according to the preterm feeding cues coding
      system (PFCCS) from 7 paired maternal-infant feeding videos that featured preterm
      infants of 25 to 32 weeks gestational age at birth. RESULTS: The PFCCS classifies
      24 feeding behavioral cues into hunger cues, self-regulatory cues, stress cues,
      and satiety cues. Infants in the breastfeeding group had a higher hunger cue
      frequency than their bottle-fed peers (p = .013), while bottle-fed infants had a
      higher stress cue frequency than their breastfed peers (p = .041). Other
      significant differences in behavioral cues between the two feeding methods
      included "fluid spillage" (bottle- >breast-, p = .008), "central cyanosis"
      (bottle- >breast-, p = .024) and "hand pushing" (breast- >bottle-, p = .034).
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Preterm infants in this study who
      breastfed showed significantly fewer stress cues than those who bottle fed. These
      findings support the importance of enhancing care provider sensitivity with
      regard to behavioral-cue observation. Findings further support breastfeeding
      rather than bottle-feeding for preterm infants.

PMID- 24310552
TI  - [Factors influencing the participation of post coronary artery bypass patients in
      cardiac rehabilitation exercise].
AB  - BACKGROUND: Studies have shown that cardiovascular rehabilitation exercise
      improves quality of life in post-coronary-bypass-surgery patients. However, the
      rate of participation in this exercise by this patient group in Taiwan has
      increased only 8.2% during the past 13 years (from 61.9% in 1996 to 70.1% in
      2009). Little is known about the factors that influence patient motivation to
      participate in cardiovascular rehabilitation exercise. PURPOSE: This study
      explores the factors that influence patient participation in rehabilitation
      exercise following coronary bypass surgery. METHODS: This cross-sectional,
      correlational study recruited a convenience sample of 253 patients who had
      undergone coronary bypass surgery at a medical center in southern Taiwan.
      Structured questionnaires, including a patient rehabilitation exercise experience
      questionnaire, Short Form-36 Health Survey-Taiwan Form, and cardiac
      rehabilitation exercise design factors questionnaire were used for data
      collection. SPSS19.0 was used to analyze data. RESULTS: The variables "healthcare
      provider recommendation of rehabilitation exercise", "exercise program
      accessibility", "physical health status", and "patient post-surgical exercise
      patterns" each had a significant influence on participant participation in post
      surgical rehabilitation exercise. Binary logistic regression analyses identified
      "receiving information on rehabilitation exercise", "level of patient-perceived
      importance of rehabilitation exercise", and "having post-surgical exercise
      patterns" as important predictors of participation in a rehabilitation exercise
      program, with OR ratios of 112, 7.86, and 3.23 times respectively. These 3
      factors accounted for 90.1% of the total variance. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: Patient education on coronary bypass post-surgical rehabilitation
      exercise programs should be emphasized during pre-surgical consultation and care
      in order to facilitate the recovery of normal life functions following coronary
      bypass surgery.

PMID- 24310553
TI  - [The family transition experience: family-centered hospitalization care of
      bipolar disorder patients].
AB  - BACKGROUND: Differences in cognition and attitudes between bipolar disorder
      patients and their families frequently result in differences between the two in
      terms of opinions and perceptions on appropriate medical treatments and
      prognoses. Transforming patient-centered-care psychotherapy into an intervention
      that provides family-focused nursing, promotes interaction among family members,
      and changes communication styles may assist families to adapt and focus on
      pursuing the soundest medical treatment. PURPOSE: This qualitative study explores
      the healing process of family transition in terms of family-centered care for
      bipolar disorder patients and nursing strategy intervention. METHODS: A
      psychiatric nurse with clinical experience used four 60-90 minute semi
      structured, in-depth interviews to collect data from 8 families. The process was
      recorded and transcribed verbatim. Content analysis was used to analyze and
      categorize the major themes. RESULTS: Results were generalized into three themes
      that addressed the interaction-in-transition between patients and their families.
      These themes were: "All of the blame comes from the disease", "There is love in
      the family", and "Agreement to start over". Nurses increased their positive
      interaction with the family by facilitating cognitive, emotional, and behavioral
      change in the family. The 3 nursing strategy interventions used in this study to
      promote family adaptation in this study were: (1) guiding family experiences of
      the disease situation; (2) inspiring the potential strength in the families; (3)
      mobilizing the internal and external resources of families.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Nurses may help family healing by
      identifying family strengths and resources, looking for solutions to problems,
      transforming effective communicating style, and making family contracts.

PMID- 24310554
TI  - [The status of the psychiatric nurse as a guarantor in Taiwan: a case study].
AB  - BACKGROUND: Psychiatric nurses have a special obligation and legal duty as
      guarantor against criminal negligence. The guarantor role and medical negligence
      in psychiatric nursing are topics that have been neglected in Taiwan. PURPOSE:
      (1) Identify the status of psychiatric nurses as guarantors; (2) Understand the
      causal relationship in a legal context between this status and Non-Genuine
      Omission in the current case; (3) Understand the facts and the dispute in the
      current case. (4) Explore the reasons why the psychiatric nurse was convicted for
      criminal negligence in the current case. METHODS: A literature review and case
      study were used to analyze the high court criminal judgment and sentence
      reconsideration of the first instance No. 122 (2005). RESULTS: (1) Psychiatric
      nurses hold two guarantor roles in Taiwan. One role is as legally protected
      interest guarantor and the other is as supervisors' dangerous source guarantor.
      (2) The three sources of guarantor status relevant to the current case are:
      nurses' voluntary commitments; medical contract; duty of care of supervisors. (3)
      In this case, the psychiatric nurse did not discharge her obligations as
      guarantor and failed to prevent the patient from committing suicide. Negligence
      resulted in patient death and the psychiatric nurse was found guilty.
      CONCLUSIONS: In order to prevent criminal acts, psychiatric nurses should gain a
      better understanding of their status as guarantor and the obligations entailed in
      this status. This article is intended to assist psychiatric nurses understand
      their responsibilities under current laws.

PMID- 24310555
TI  - [Project to improve the free flap survival rate in oral cancer
      microreconstruction free flap surgery].
AB  - BACKGROUND&PROBLEMS: Free-flap thrombosis risk factors affect the success of
      microreconstruction surgery that involves the use of a free flap. The free flap
      survival rate in our unit was 92.65%. Relevant risk factors identified included:
      (1) poor nursing assessment cognizance and low accuracy rates; (2) lack of
      standardized of postoperative monitoring protocols; (3) lack of assessment tools;
      (4) inadequate inter-team communication; and (5) lack of a free flap care
      monitoring audit. PURPOSE: The purpose of this project was to improve the free
      flap survival rate from 92.65% to at least 97%. RESOLUTIONS: The authors: (1)
      held relevant educational training programs; (2) evaluated nurse skills in
      clinical settings; (3) established a standardized nursing monitoring protocol;
      (4) provided sufficient assessment equipment; (5) improved inter-team
      communication mechanisms; and (6) formulated a monitoring audit protocol.
      RESULTS: The free flap survival rate rose from 92.65% to 100%, with no failed
      flaps during the assessment period December 2011 to May 2012. CONCLUSIONS: The
      resolutions proposed by this project may significantly improve the free flap
      survival rate.

PMID- 24310556
TI  - [A project to improve the follow-up completion rate of colorectal cancer
      screening-positive patients].
AB  - BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths
      in Taiwan. Patients diagnosed early have excellent cure rates. Mackay Memorial
      Hospital, working on a Bureau of Health Promotion (BHP) project, found the
      colorectal cancer screening completion rate for positive patients to be the
      lowest among four cancer screenings reviewed. We thus formed a project team to
      improve the follow-up completion rate for colorectal cancer screening-positive
      patients. PURPOSE: This project was designed to raise the follow-up completion
      rate for colorectal cancer screening-positive patients to 65%. METHODS: Explicit
      interventions implemented included making health education leaflets and return
      visit reminder sheets, holding/organizing screening seminars, opening a
      consultation helpline, formulating follow-up colorectal cancer screening
      procedures for screening-positive patients, holding hospital educational training
      courses, establishing cross-unit collaboration models, and benchmarking other
      hospitals. RESULTS: The follow-up completion rate increased from 53.63% to
      66.08%. CONCLUSIONS: Conducting health education programs and strengthening team
      awareness of follow-up completion rates effectively enhanced the follow-up
      completion rate for colorectal cancer screening-positive patients and improved
      medical care quality.

PMID- 24310557
TI  - [Caring for families of charcoal-burning suicide patients].
AB  - Charcoal-burning is the second major cause of suicide death in Taiwan. Predicting
      the variable damage and sequelae in this suicide mode is difficult due to the
      rapid combination of carbon monoxide with red blood cells. Delayed
      neuropsychological sequelae (DNS) may result in significantly extended recovery
      times, causing additional stress to the family. Nurses may help increase family
      understanding and support and guide family members to more positive intra-family
      interactions, shared perspectives on the recovery process, and resource seeking
      behavior by depicting subsequent family life and helping the entire family
      develop coping strategies those allow all members to effect cognitive, emotional
      and behavioral change. This result may help families of attempted suicide
      individuals recover successfully. 

PMID- 24310558
TI  - [Paternal grief and nursing care in perinatal deaths].
AB  - Perinatal death distresses all family members. Paternal perceptions of perinatal
      death should be better understood in order to help the expectant father maintain
      long-term health and quality of life and minimize the potential negative effects
      of paternal grieving and stress on family and marital relations. Male and female
      grieving behaviors have been shown to differ significantly. Taiwan society
      typically expects males to be strong and support the family while avoiding the
      overt expression or revelation of personal feelings such as grief, regret, and
      anger. Although fathers may be reluctant to express a need for care, care
      personnel may facilitate care through such activities as understanding of a
      perinatal-death father's feelings, providing related messages about the event to
      facilitate good decisions, helping him support his spouse, helping him adopt
      appropriate behaviors and attitudes toward the fetus, and treating him as a
      grieving father rather than a medical event. This article reviews the literature
      to explore paternal perceptions and reactions toward perinatal death in order to
      recognize nursing needs and principles of grieving fathers within the Taiwan
      cultural context. Further study in this area is recommended.

PMID- 24310559
TI  - [The development of forensic nursing from the perspective of domestic violence
      and sexual assault preventive policies].
AB  - Forensic nursing is a new nursing specialty that provides forensic nursing
      service to domestic violence victims and offenders. Development of the role of
      forensic nurses has become urgent and necessary. The high rates of domestic
      violence and sexual assault in Taiwan suggest that forensic nurses have an
      important role to play in domestic healthcare. This article highlights the
      significance of forensic nursing in Taiwan in the future in terms of its origin,
      definitions, models, roles and functions, training and education, and previous
      studies. Through cooperation among academia, government, industry, and law
      enforcement agencies, it is expected that forensic nursing will be a positive and
      important area of expansion for professional nursing. 

PMID- 24310560
TI  - [Neonatal asphyxia: a care experience using hypothermic therapy].
AB  - Hypothermia therapy, used to treat hypoxic-ischemic encephalopathy in neonates,
      has been shown to effectively decrease asphyxia complications and mortality. This
      article reports on an experience using this therapy approach to care for a
      neonatal asphyxic patient. Due to our lack of an appropriate cooling device, we
      adjusted the number of cool water bags to successfully perform hypothermic
      therapy. Despite this added procedural complication, we succeeded in saving the
      patient's life. The holistic care process for this type of case requires family
      centered care to help family members deal with the critical condition and assist
      parents to face depression and guilt, reduce anxiety, and reaffirm the parent
      child relationship. We used hypothermia in the initial stage. Relevant standards
      of critical care for this condition should be established to ensure adequate
      nursing care safety and quality. 

PMID- 24310561
TI  - Islet infiltration, cytokine expression and beta cell death in the NOD mouse, BB
      rat, Komeda rat, LEW.1AR1-iddm rat and humans with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Research on the pathogenesis of type 1 diabetes relies heavily
      on good animal models. The aim of this work was to study the translational value
      of animal models of type 1 diabetes to the human situation. METHODS: We compared
      the four major animal models of spontaneous type 1 diabetes, namely the NOD
      mouse, BioBreeding (BB) rat, Komeda rat and LEW.1AR1-iddm rat, by examining the
      immunohistochemistry and in situ RT-PCR of immune cell infiltrate and cytokine
      pattern in pancreatic islets, and by comparing findings with human data. RESULTS:
      After type 1 diabetes manifestation CD8(+) T cells, CD68(+) macrophages and
      CD4(+) T cells were observed as the main immune cell types with declining
      frequency, in infiltrated islets of all diabetic pancreases. IL-1beta and TNF
      alpha were the main proinflammatory cytokines in the immune cell infiltrate in
      NOD mice, BB rats and LEW.1AR1-iddm rats, as well as in humans. The Komeda rat
      was the exception, with IFN-gamma and TNF-alpha being the main cytokines. In
      addition, IL-17 and IL-6 and the anti-inflammatory cytokines IL-4, IL-10 and IL
      13 were found in some infiltrating immune cells. Apoptotic as well as
      proliferating beta cells were observed in infiltrated islets. In healthy
      pancreases no proinflammatory cytokine expression was observed.
      CONCLUSIONS/INTERPRETATION: With the exception of the Komeda rat, the animal
      models mirror very well the situation in humans with type 1 diabetes. Thus animal
      models of type 1 diabetes can provide meaningful information on the disease
      processes in the pancreas of patients with type 1 diabetes.

PMID- 24310562
TI  - Reduction of non-esterified fatty acids improves insulin sensitivity and lowers
      oxidative stress, but fails to restore oxidative capacity in type 2 diabetes: a
      randomised clinical trial.
AB  - AIMS/HYPOTHESIS: Muscle mitochondrial function can vary during fasting, but is
      lower during hyperinsulinaemia in insulin-resistant humans. Ageing and
      hyperlipidaemia may be the culprits, but the mechanisms remain unclear. We
      hypothesised that (1) insulin would fail to increase mitochondrial oxidative
      capacity in non-diabetic insulin-resistant young obese humans and in elderly
      patients with type 2 diabetes and (2) reducing NEFA levels would improve insulin
      sensitivity by raising oxidative capacity and lowering oxidative stress. METHODS:
      Before and after insulin (4, 40, 100 nmol/l) stimulation, mitochondrial oxidative
      capacity was measured in permeabilised fibres and isolated mitochondria using
      high-resolution respirometry, and H2O2 production was assessed fluorimetrically.
      Tissue-specific insulin sensitivity was measured with hyperinsulinaemic
      euglycaemic clamps combined with stable isotopes. To test the second hypothesis,
      in a 1-day randomised, crossover study, 15 patients with type 2 diabetes
      recruited via local advertisement were assessed for eligibility. Nine patients
      fulfilled the inclusion criteria (BMI <35 kg/m(2); age <65 years) and were
      allocated to and completed the intervention, including oral administration of 750
      mg placebo or acipimox. Blinded randomisation was performed by the pharmacy; all
      participants, researchers performing the measurements and those assessing study
      outcomes were blinded. The main outcome measures were insulin sensitivity,
      oxidative capacity and oxidative stress. RESULTS: Insulin sensitivity and
      mitochondrial oxidative capacity were ~31% and ~21% lower in the obese groups
      than in the lean group. The obese participants also exhibited blunted substrate
      oxidation upon insulin stimulation. In the patients with type 2 diabetes,
      acipimox improved insulin sensitivity by ~27% and reduced H2O2 production by
      ~45%, but did not improve basal or insulin-stimulated mitochondrial oxidative
      capacity. No harmful treatment side effects occurred. CONCLUSIONS/INTERPRETATION:
      Decreased mitochondrial oxidative capacity can also occur independently of age in
      insulin-resistant young obese humans. Insulin resistance is present at the muscle
      mitochondrial level, and is not affected by reducing circulating NEFAs in type 2
      diabetes. Thus, impaired plasticity of mitochondrial function is an intrinsic
      phenomenon that probably occurs independently of lipotoxicity and reduced glucose
      uptake. TRIAL REGISTRATION: Clinical Trials NCT00943059 FUNDING: This study was
      funded in part by a grant from the German Federal Ministry of Education and
      Research to the German Center for Diabetes Research (DZD e.V.).

PMID- 24310563
TI  - Laparoscopic adjustable gastric banding and progression from impaired fasting
      glucose to diabetes.
AB  - AIMS/HYPOTHESIS: Obesity and dysglycaemia are major risk factors for type 2
      diabetes. We determined if obese people undergoing laparoscopic adjustable
      gastric banding (LAGB) had a reduced risk of progressing from impaired fasting
      glucose (IFG) to diabetes. METHODS: This was a retrospective cohort study of
      obese people with IFG who underwent LAGB. Weight and diabetes outcomes after a
      minimum follow-up period of 4 years (mean +/- SD 6.1 +/- 1.7 years) were compared
      with those of Australian adults with IFG from a population-based study (AusDiab).
      RESULTS: We identified 281 LAGB patients with baseline IFG. Their mean +/- SD age
      and BMI were 46 +/- 9 years and 46 +/- 9 kg/m(2), respectively. The diabetes
      incidence for patients in the lowest, middle and highest weight loss tertile were
      19.1, 3.4 and 1.8 cases/1,000 person-years, respectively. The AusDiab cohort had
      a lower BMI (28 +/- 5 kg/m(2)) and a diabetes incidence of 12.5 cases/1,000
      person-years. This increased to 20.5 cases/1,000 person-years when analysis was
      restricted to the 322 obese AusDiab participants, which was higher than the
      overall rate of 8.2 cases/1,000 person-years seen in the LAGB group (p = 0.02).
      Multivariable analysis of the combined LAGB and AusDiab data suggested that LAGB
      was associated with ~75% lower risk of diabetes (OR 0.24 [95% CI 0.10, 0.57], p =
      0.004). CONCLUSIONS/INTERPRETATION: In obese people with IFG, weight loss after
      LAGB is associated with a substantially reduced risk of progressing to diabetes
      over >=4 years. Bariatric surgery may be an effective diabetes prevention
      strategy in this population.

PMID- 24310564
TI  - Identification and DNA sequence analysis of a gamma-type gliadin cDNA plasmid
      from winter wheat.
AB  - Recombinant cDNA plasmids possessing the coding sequences for the gamma-type
      gliadins were isolated from a cDNA library prepared from wheat seed poly (A(+))
      RNA. One of these plasmids, pGliB48, specifically hybridizes to poly (A(+)) RNA
      molecules 1 400-1 500 bases in length that direct the synthesis of polypeptides
      at 38 Kd and 46 Kd, the latter size characteristic of the gamma-type gliadins.
      The cDNA sequence of pGliB48 was determined and encompasses the 3' untranslated
      region as well as 245 amino acids from the C-terminus of the gamma-type gliadin
      polypeptide. The 5'-end of the DNA coding sequence consists of a tandem repeat
      unit composed of eight amino acids. Localized regions of homology are observed
      for the alpha/beta-type and gamma-type gliadin cDNA sequences. 

PMID- 24310565
TI  - Silent T-DNA genes in plant lines transformed by Agrobacterium tumefaciens are
      activated by grafting and by 5-azacytidine treatment.
AB  - A shooty tumor induced by a shooter mutant of an octopine strain of Agrobacterium
      tumefaciens was cloned. One clone obtained (TS038) behaved aberrantly in that it
      grew as a shooty tumor tissue on phytohormone free medium, but did not contain
      octopine synthase activity. In line TS038 the genes for octopine synthase and for
      the enzymes involved in agropine and mannopine synthesis were present, but were
      not transcribed. However, the above genes became active in TS038 tumor shoots
      after grafting as well as after treatment with the hypomethylating agent 5
      azacytidine. After an unusually long incubation period in the growth cabinet
      shoot cultures appeared to have developed small shoots from the top of the
      leaves. This unusual form of differentiation was found to be accompanied by the
      induction of octopine synthase activity. 

PMID- 24310566
TI  - Tumor formation on plants by mixtures of attenuated Agrobacterium tumefaciens T
      DNA mutants.
AB  - The inoculation of plants with mixtures consisting of an A. tumefaciens mutant
      with a mutation in the auxin-locus of the T-DNA and a mutant with a mutation in
      the cytokinin-locus of the T-DNA invariably led to full tumor induction, in spite
      of the low oncogenicity of each of the mutants when inoculated separately. A
      similar complementation was observed when mixtures of certain auxin-locus mutants
      were used for infection. In these experiments the auxin-locus mutants fell into
      two classes. One class appeared to have mutations in the T-DNA region for
      transcript 1, while the other class had a mutation in the region for transcript
      2. The intra-locus complementation observed suggests that the T-DNA genes in the
      auxin-locus together determine the production of a trans-acting product. 

PMID- 24310567
TI  - Contribution of processing events to the molecular heterogeneity of four banding
      types of phaseolin, the major storage protein of Phaseolus vulgaris L.
AB  - The origin of the molecular heterogeneity of phaseolin was investigated by
      studying, both in vivo and in vitro, the synthesis and processing of four
      different banding types of phaseolin in five cultivars of Phaseolus vulgaris L.
      The results demonstrate: I) Newly-synthesized (unprocessed) phaseolin in all
      cultivars is composed of three major components. These differ between cultivars,
      both in charge and Mr. II) The processing of these precursors is highly conserved
      and consists of the co-translational cleavage of a signal peptide, two
      glycosylation steps in the endoplasmic reticulum and a further modification
      inside the protein bodies to give the mature form. III) Some of the molecular
      heterogeneity of each phaseolin banding type is due to a different extent of
      glycosylation of its polypeptide components. 

PMID- 24310568
TI  - Homology between the ribosomal DNA of Escherichia coli and mitochondrial DNA
      preparations of maize is principally to sequences other than mitochondrial rRNA
      genes.
AB  - E. coli ribosomal DNA has been used to probe maize mitochondrial DNA. It
      hybridizes primarily with chloroplast ribosomal DNA sequences and with fungal and
      bacterial sequences which may contaminate the mtDNA preparations. It also
      hybridizes to the chloroplast 16S ribosomal RNA gene sequence present in the
      mitochondrial genome (1) as well as to the mitochondrial 18S ribosomal RNA gene
      sequence. Weak sequence homology was detected between E. coli rDNA and the
      mitochondrial 26S ribosomal RNA gene. 

PMID- 24310569
TI  - Sequence homology between the 32K dalton and the D2 chloroplast membrane
      polypeptides of Chlamydomonas reinhardii.
AB  - The region of the chloroplast genome of Chlamydomonas reinhardii containing the
      gene of the thylakoid polypeptide D2 (psbD) has been sequenced. A unique open
      reading frame of 350 codons exists in this region. Because the first ATG is
      followed 11 codons downstream by a second one, the D2 polypeptide consists of
      either 339 or 350 amino acids. Comparison of the sequences of D2 and the 32K
      dalton polypeptides, both of which are associated with photosystem II, reveals
      partial homology. Although, the overall homology of these two polypeptides is
      only 27%, they contain several related regions and their hydropathic profiles are
      strikingly similar. These data suggest that the two polypeptides may have related
      functions and/or that their genes may have originated from a common ancestor.
      Alternatively, convergent evolution of these polypeptides may be due to
      structural constraints in the thylakoid membrane. Limited sequence homology is
      also observed between the D2 polypeptide and some of the subunits of the reaction
      centers of photosynthetic bacteria. 

PMID- 24310570
TI  - In vitro transformation of petunia cells by an improved method of co-cultivation
      with A. tumefaciens strains.
AB  - A method (termed co-cultivation) for transforming plant cells in vitro with A.
      tumefaciens strains, which was originally developed by Marton et al. (1978)
      Nature 277: 129-131, has been modified by the incorporation of a novel feeder
      plate culture system and been extended to use with petunia protoplasts. Using
      efficient cell plating and selection conditions for phytohormone-independent
      growth, large numbers of independent transformed calli can be obtained
      efficiently (~10(-1)) and in less than 3 weeks following protoplast isolation.
      Southern hybridization analysis has confirmed that the majority of the resulting
      in vitro transformants contain a single copy of full length T-DNA.The high
      efficiency of this procedure allows simple screening to identify plant cells
      transformed by Ti plasmids attenuated by deletion of internal T-DNA regions.
      Results are presented that demonstrate the co-cultivation method can be used in
      conjunction with short term assays for monitoring plant gene expression. 

PMID- 24310571
TI  - Homology between the proteins encoded by tobacco mosaic virus and two
      tricornaviruses.
AB  - A comparison was made of the amino acid sequences of the proteins encoded by RNAs
      1 and 2 of alfalfa mosaic virus (A1MV) and brome mosaic virus (BMV), and the 126K
      and 183K proteins encoded by tobacco mosaic virus (TMV). Three blocks of
      extensive homology of about 200 to 350 amino acids each were observed. Two of
      these blocks are located in the A1MV and BMV RNA 1 encoded proteins and the TMV
      encoded 126K protein; they are situated at the N-terminus and C-terminus,
      respectively. The third block is located in the A1MV and BMV RNA 2 encoded
      proteins and the C-terminal part of the TMV encoded 183K protein. These
      homologies are discussed with respect to the functional equivalence of these
      putative replicase proteins and a possible evolutionary connection between A1MV,
      BMV and TMV. 

PMID- 24310572
TI  - Cellulase gene expression in ripening avocado fruit: The accumulation of
      cellulase mRNA and protein as demonstrated by cDNA hybridization and
      immunodetection.
AB  - A cDNA library was constructed from poly(A)(+)RNA of ripe avocado fruit. Colony
      hybridization identified a number of ripening specific clones of which one, pAV5,
      was shown to be specific for cellulase. Hybrid selection with pAV5 provided a
      message from ripe fruit that on in vitro translation yielded a polypeptide of
      53kD, comigrating with purified avocado cellulase on SDS polyacrylamide gel
      electrophoresis. The translation product was selectively immunoprecipitated by
      antiserum to purified avocado cellulase. Immunoblotting of unripe and ripe
      avocado fruit extracts following SDS-PAGE showed a plentiful immunoreactive
      polypeptide in ripe fruit, and essentially none in unripe fruit. Hybridization of
      pAV5 to poly(A)(+)-RNA from unripe and ripe avocado fruit demonstrated that there
      is at least a 50-fold increase in the cellulase message concentration during
      ripening. Thus, the expression of cellulase enzyme activity during ripening is
      regulated by the appearance of mRNA coding for cellulase rather than by either
      translational or post-translational control mechanisms. 

PMID- 24310573
TI  - Ethylene-regulated gene transcription in carrot roots.
AB  - The plant hormone ethylene elicits many biochemical changes in target tissues. To
      investigate ethylene effects on expression of genetic information, cDNA clones
      corresponding to ethylene-induced carrot root mRNAs were constructed and
      isolated. RNA dot blot analysis showed that for the three clones studied peak
      cytosolic mRNA prevalence occurred at 21 h of treatment followed thereafter by
      rapid messenger decay. DNA filter excess hybridization to in vitro synthesized
      nuclear RNA showed that the ethylene-induced mRNA increase is engendered by
      transcription of previously quiescent genes. The kinetics and magnitude of
      changes in mRNA prevalence parallel changes in transcriptional activity;
      therefore the ethylene effect is primarily at the level of transcription. In vivo
      pulse labelling with [(35)S]-methionine showed that between 18 and 27 h of
      ethylene treatment a 2.5 fold increase in translational efficiency occurred for
      one message studied. The resulting protein is the predominant protein synthesized
      in carrots treated with ethylene for 27 h. Thus ethylene seemingly exerts
      multiple regulatory controls on the expression of genetic information. 

PMID- 24310574
TI  - Determination of the translation start site of the large subunit of ribulose-1,5
      bisphosphate carboxylase from maize.
AB  - Sequence studies of the gene for the large subunit of ribulose-1,5-bisphosphate
      carboxylase from maize indicate the presence of two translation start sites, 18
      bp apart. Each site is preceded by a suitable ribosome binding region. By using a
      simplified E. coli-based in vitro system which measures fromation of the first
      dipeptide of the gene product, we have determined that only the second methionine
      initiates translation. 

PMID- 24310575
TI  - The effects of gibberellic acid and abscisic acid on alpha-amylase mRNA levels in
      barley aleurone layers studies using an alpha-amylase cDNA clone.
AB  - Two cDNA clones were characterized which correspond to different RNA species
      whose level is increased by gibberellic acid (GA3) in barley (Hordeum vulgare L.)
      aleurone layers. On the criteria of amino terminal sequencing, amino acid
      composition and DNA sequencing it is likely that one of these clones (pHV19)
      corresponds to the mRNA for alpha-amylase (1,4-alpha-D-glucan glucanohydrolase,
      EC 3.2.1.1.), in particular for the B family of alpha-amylase isozymes (Jacobsen
      JV, Higgins TJV: Plant Physiol 70:1647-1653, 1982). Sequence analysis of PHV19
      revealed a probable 23 amino acid signal peptide. Southern hybridization of this
      clone to barley DNA digested with restriction endonucleases indicated
      approximately eight gene-equivalents per haploid genome.The identity of the other
      clone (pHV14) is unknown, but from hybridization studies and sequence analysis it
      is apparently unrelated to the alpha-amylase clone.Both clones hybridize to RNAs
      that are similar in size (~1500b), but which accumulate to different extents
      following GA3 treatment: alpha-amylase mRNA increases approximately 50-fold in
      abundance over control levels, whereas the RNA hybridizing to pHV14 increases
      approximately 10-fold. In the presence of abscisic acid (ABA) the response to GA3
      is largely, but not entirely, abolished. These results suggest that GA3 and ABA
      regulate synthesis of alpha-amylase in barley aleurone layers primarily through
      the accumulation of alpha-amylase mRNA. 

PMID- 24310576
TI  - Phytohormone control of translatable RNA populations in sexual organogenesis of
      the dioecious plant Mercurialis annua L. (2n = 16).
AB  - A cell-free translation system was programmed with total, poly(A), non poly(A)
      and polysomal RNAs from male and female flowers of this plant with separated
      sexes. The peptide patterns obtained reflected differences in corresponding
      translatable RNAs. In total RNA products, three peptides were specific for males,
      two for females. One of the two male-specific polypeptides of high molecular
      weight was obtained from poly(A) RNAs and a female-specific one from non poly(A)
      RNAs. Differences between peptides common to both sexes reflected different
      concentrations of corresponding messengers. Similar results were obtained with
      polysomal RNAs. The male-specific RNAs were depending on high endogenous auxin
      concentrations while the female on active cytokinins. Cytokinin feminization of
      males induced the female-specific RNAs showing cytokinin action at
      pretranslational stages. Phytohormone roles are discussed. 

PMID- 24310577
TI  - Molecular biology of C4 photosynthesis in Zea mays: differential localization of
      proteins and mRNAs in the two leaf cell types.
AB  - We have investigated the molecular basis of differential localization of enzyme
      activities in mesophyll(M) and bundle-sheath (B) cells of maize leaves. M
      protoplasts and B strands were prepared by enzymatic digestions and mechanical
      treatment of secondary leaves. Soluble and thylakoid membrane proteins from the
      two cell types were compared by one- and two-dimensional gel electrophoresis and
      quantitative rocket immunoelectrophoresis. In addition, several thylakoid
      polypeptides were identified by crossed immunoelectrophoresis using monospecific
      antibodies. M and B thylakoids show quantitative and qualitative differences in
      their polypeptide compositions. While the M thylakoids contain the normal
      complement of polypeptides, the B thylakoids are deficient in ferredoxin-NADP(+)
      reductase, photosystem II reaction center polypeptides, and the light-harvesting
      chlorophyll a/b-protein complex. Comparison of the soluble proteins by two
      dimensional gel electrophoresis revealed marked differences between M and B
      cells. The major proteins of one cell type are clearly absent from the other.
      These differences are paralleled by differences in the in vitro translation
      products of poly A(+) RNA isolated from the two cell types. Immunoprecipitation
      experiments showed that mRNA encoding the small subunit of ribulose-1,5
      bisphosphate carboxylase (rbcS) is localized exclusively in B cells, whereas mRNA
      encoding phosphoenolpyruvate carboxylase is detected only in M cells. cDNA clones
      encoding the carboxylase rbcS and the chlorophyll a/b binding protein were used
      as probes in Northern blot analysis. M cells contain no detectable RNA encoding
      rbcS but have a higher steady state level of RNA encoding the chlorophyll a/b
      binding polypeptide compared to B cells. Taken together, our results demonstrate
      that differential gene expression in the two leaf cell types is regulated at the
      level of translatable mRNA, and, for at least two proteins, at the level of
      steady-state RNA. 

PMID- 24310578
TI  - Microanalysis of plant mitochondrial protein synthesis products: : Detection of
      variant polypeptides associated with cytoplasmic male sterility.
AB  - A mitochondrial fraction obtained from 0.5 g of leaves was purified on a 0.75 ml
      Percoll gradient and used for an in vitro mitochondrial protein synthesis assay
      in the presence of [(35)S] methionine. A set of 15 to 20 labeled polypeptides
      were revealed by autoradiography after sodium dodecylsulfate polyacrylamide gel
      electrophoresis. This could be applied at an early growth stage by using a few
      leaves from individual seedlings. It revealed the presence of variant
      mitochondrially translated polypeptides in green leaves of cytoplasmic male
      sterile lines from various cultivated plants of large economic importance: maize,
      wheat, sugar beet, tobacco and faba bean. This non-destructive microanalysis is
      thus of general use and opens new possibilities for rapid and large mass
      screening of mitochondrial parameters such as male sterility. 

PMID- 24310579
TI  - Inexpensive method of liposuction cannula port-site protection.

PMID- 24310580
TI  - The effectiveness and safety of combining laser-assisted liposuction and
      abdominoplasty.
AB  - BACKGROUND: Lipoabdominoplasty is nearly a daily aesthetic procedure. Despite the
      emergence of laser-assisted liposuction, to date, it has not been clearly
      evaluated combined with abdominoplasty. This prospective study aimed to evaluate
      the effectiveness and safety of laser-assisted liposuction relative to
      traditional liposuction combined with high-lateral-tension abdominoplasty.
      METHODS: This study investigated 36 consecutive female patients who underwent
      high-lateral-tension abdominoplasty combined with liposuction of the upper
      central abdomen and both flanks. The patients were divided into three equal
      groups based on the technique used for liposuction. Group 1 underwent
      conventional liposuction with abdominoplasty. Group 2 underwent a mixture of
      conventional and laser-assisted liposuction with abdominoplasty. Group 3
      underwent laser-assisted liposuction with abdominoplasty. RESULTS: The patients
      in groups 2 and 3 had a better aesthetic outcome than those in group 1 with
      regard to abdominal contour and skin tightness. No major complications were
      observed in groups 1 and 2. The patients in group 3 had a higher incidence of
      complications (3 seromas, 3 central necroses and dehiscence), and one patient
      underwent secondary sutures. CONCLUSION: Laser-assisted liposuction combined with
      abdominoplasty in the lateral abdomen seems to be a safe technique with good
      aesthetic outcomes. Although the combined use of laser-assisted liposuction in
      the lateral and central abdomen can achieve relatively better aesthetic results,
      it is associated with significant complications, and its use cannot be supported.
      Proper laser parameters in the central abdominal area still need further study.
      LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 24310581
TI  - No osteotomy rhinoplasty: indications and surgical details.
AB  - Lateral osteotomy is a particular step in rhinoplasty that aims to close an open
      roof deformity after hump reduction, narrow the lateral walls of the nose, and
      symmetrically align the nasal bony framework in cases with asymmetry. When the
      only reason for performing lateral osteotomy is to close an open roof, this can
      be avoided by using auto spreader flaps. In component hump reduction, the entire
      length of the upper lateral cartilage is preserved, including the portion under
      the nasal bone bilaterally. The basic principles involve suturing the flaps in
      the midline with a modified technique and supporting the lateral nasal walls with
      onlay cartilage grafts. This method was used for 34 patients. The lack of lateral
      wall support was obvious in one of the patients. With precise indications and a
      well-designed surgery, can be achieved. Further studies with more patients and a
      longer follow-up period are needed to determine the accuracy of this philosophy.
      LEVEL OF EVIDENCE V: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 24310582
TI  - Correction of asymmetric pectus excavatum using a virtually designed silicone
      implant.
AB  - BACKGROUND: An extended asymmetric funnel chest deformity with the breast gland
      located in the thoracic mold can lead to a fictitious aplasia of the breast. The
      authors termed this condition "pseudo-Amazon syndrome" because the breast tissue
      and the pectoralis muscle are fully developed. METHODS: This report presents a
      detailed technical approach to the fabrication of a precise-fitting custom-made
      silicone implant. The design of the implant was achieved using a computed
      tomography (CT) data set and rapid prototyping. The volumes of the "hidden" and
      the normal breasts measured preoperatively by processing the CT data were
      similar. These volumes were compared with the breast volumes measured by three
      dimensional photography 4 years postoperatively to assess the predictability of
      the volume congruency. The silicone implant was surgically placed in the
      epicostal plane and extended almost over the right hemithorax. RESULTS: The
      implantation was performed without the necessity of further trimming. Both the
      surgeon and the patient rated the aesthetic and functional long-term result as
      good in terms of symmetry and the possibility of exercise without restrictions.
      The final breast volume of the surgically treated side was 95 % of the volume of
      the normal contralateral breast. CONCLUSION: The described method reduces the
      operation time and the operative trauma by primary implant fit. However, the
      method is rather elaborate and the production process is expensive. This in turn
      reduces the generation of proceeds to a minimum. LEVEL OF EVIDENCE V: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24310583
TI  - Interactions between accumulated copper, bacterial community structure and
      histamine levels in crayfish meat during storage.
AB  - BACKGROUND: Pollution in aquaculture areas may negatively impact edible species
      and threaten seafood quality and safety. The aim of this study was to determine
      the interaction between copper and bacteria in the aquatic habitat and their
      impact upon crustaceans. Marbled crayfish was chosen as a model of aquatic
      crustaceans and the influence of metal contamination on bacterial community
      structure in water used to culture crayfish and in crayfish themselves was
      investigated. Histamine, an allergen commonly formed by certain groups of
      bacteria in crustacean edible tissue during storage, was also determined.
      RESULTS: Copper exposure increased its concentration in crayfish meat by 17.4%,
      but the copper concentration remained within acceptable food safety limits.
      Elevated copper levels affected the bacterial community both in the water used to
      cultivate crayfish and in the marbled crayfish themselves. Cluster analysis of
      16S rRNA-gene based microbial community fingerprints revealed that copper
      impacted the bacterial community in the water and in the crayfish meat. However,
      copper exposure reduced the formation of histamine in crayfish meat during
      storage by 66.3%. CONCLUSION: Copper from the habitat appears to reduce histamine
      accumulation in crayfish meat during storage by affecting the bacterial community
      structure of the cultivation water and most likely also in the intestine of the
      crayfish. From a food safety point of view, copper treatment during the aqua
      culturing of crustaceans has a positive impact on the postharvest stage.

PMID- 24310584
TI  - Adenovirus Vector-Derived VA-RNA-Mediated Innate Immune Responses.
AB  - The major limitation of the clinical use of replication-incompetent adenovirus
      (Ad) vectors is the interference by innate immune responses, including induction
      of inflammatory cytokines and interferons (IFN), following in vivo application of
      Ad vectors. Ad vector-induced production of inflammatory cytokines and IFNs also
      results in severe organ damage and efficient induction of acquired immune
      responses against Ad proteins and transgene products. Ad vector-induced innate
      immune responses are triggered by the recognition of Ad components by pattern
      recognition receptors (PRRs). In order to reduce the side effects by Ad vector
      induced innate immune responses and to develop safer Ad vectors, it is crucial to
      clarify which PRRs and which Ad components are involved in Ad vector-induced
      innate immune responses. Our group previously demonstrated that myeloid
      differentiating factor 88 (MyD88) and toll-like receptor 9 (TLR9) play crucial
      roles in the Ad vector-induced inflammatory cytokine production in mouse bone
      marrow-derived dendritic cells. Furthermore, our group recently found that virus
      associated-RNAs (VA-RNAs), which are about 160 nucleotide-long non-coding small
      RNAs encoded in the Ad genome, are involved in IFN production through the IFN
      beta promoter stimulator-1 (IPS-1)-mediated signaling pathway following Ad vector
      transduction. The aim of this review is to highlight the Ad vector-induced innate
      immune responses following transduction, especially VA-RNA-mediated innate immune
      responses. Our findings on the mechanism of Ad vector-induced innate immune
      responses should make an important contribution to the development of safer Ad
      vectors, such as an Ad vector lacking expression of VA-RNAs. 

PMID- 24310585
TI  - Advances in bio-optical imaging for the diagnosis of early oral cancer.
AB  - Oral cancer is among the most common malignancies worldwide, therefore early
      detection and treatment is imperative. The 5-year survival rate has remained at a
      dismal 50% for the past several decades. The main reason for the poor survival
      rate is the fact that most of the oral cancers, despite the general accessibility
      of the oral cavity, are not diagnosed until the advanced stage. Early detection
      of the oral tumors and its precursor lesions may be the most effective means to
      improve clinical outcome and cure most patients. One of the emerging technologies
      is the use of non-invasive in vivo tissue imaging to capture the molecular
      changes at high-resolution to improve the detection capability of early stage
      disease. This review will discuss the use of optical probes and highlight the
      role of optical imaging such as autofluorescence, fluorescence diagnosis (FD),
      laser confocal endomicroscopy (LCE), surface enhanced Raman spectroscopy (SERS),
      optical coherence tomography (OCT) and confocal reflectance microscopy (CRM) in
      early oral cancer detection. FD is a promising method to differentiate cancerous
      lesions from benign, thus helping in the determination of adequate resolution of
      surgical resection margin. LCE offers in vivo cellular imaging of tissue
      structures from surface to subsurface layers and has demonstrated the potential
      to be used as a minimally invasive optical biopsy technique for early diagnosis
      of oral cancer lesions. SERS was able to differentiate between normal and oral
      cancer patients based on the spectra acquired from saliva of patients. OCT has
      been used to visualize the detailed histological features of the oral lesions
      with an imaging depth down to 2-3 mm. CRM is an optical tool to noninvasively
      image tissue with near histological resolution. These comprehensive diagnostic
      modalities can also be used to define surgical margin and to provide a direct
      assessment of the therapeutic effectiveness. 

PMID- 24310586
TI  - Fliposomes: pH-Sensitive Liposomes Containing a trans-2-morpholinocyclohexanol
      Based Lipid That Performs a Conformational Flip and Triggers an Instant Cargo
      Release in Acidic Medium.
AB  - Incorporation of a pH-sensitive conformational switch into a lipid structure
      enables a drastic conformational flip upon protonation that disrupts the liposome
      membrane and causes rapid release of cargo specifically in areas of increased
      acidity. pH-sensitive liposomes containing the amphiphile (1) with trans-2
      morpholinocyclohexanol conformational switch, a phospholipid, and a PEG-lipid
      conjugate were constructed and characterized. The optimized composition
      1/POPC/PEG-ceramide (50/45/5)-could be stored at 4  degrees C and pH 7.4 for up
      to 1.5 years, and was stable in blood serum in vitro after 48 h at 37  degrees C.
      Liposomes loaded with ANTS/DPX or methotrexate demonstrated an unusually quick
      content release (in a few seconds) at pH below 5.5, which was independent of
      inter-liposome contact. The pH-titration curve for the liposome leakage
      paralleled the curve for the acid-induced conformational flip of 1 studied by 1H
      NMR. Freeze-fracture electron microscopy images showed budding and division of
      the bilayer at pH 5.5. A plausible mechanism of pH-sensitivity involves an acid
      triggered conformational flip of 1, shortening of lipid tails, and membrane
      perturbations, which cause the content leakage. The methotrexate-loaded liposomes
      demonstrated much higher cytotoxicity in HeLa cells than the free drug indicating
      that they can serve as viable drug delivery systems. 

PMID- 24310587
TI  - Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based
      Fatty Acid Amide Guanidines: Effect on Gene Silencing Efficiency.
AB  - Four guanidine derivatives of N4,N9-diacylated spermine have been designed,
      synthesized, and characterized. These guanidine-containing cationic lipids bound
      siRNA and formed nanoparticles. Two cationic lipids with C18 unsaturated chains,
      N1,N12-diamidino-N4,N9-dioleoylspermine and N1,N12-diamidino-N4-linoleoyl-N9
      oleoylspermine, were more efficient in terms of GFP expression reduction compared
      to the other cationic lipids with shorter C12 (12:0) and very long C22 (22:1)
      chains. N1,N12-Diamidino-N4-linoleoyl-N9-oleoylspermine siRNA lipoplexes resulted
      in GFP reduction (26%) in the presence of serum, and cell viability (64%). These
      data are comparable to those obtained with TransIT TKO. Thus, cationic lipid
      guanidines based on N4,N9-diacylated spermines are good candidates for non-viral
      delivery of siRNA to HeLa cells using self-assembled lipoplexes. 

PMID- 24310588
TI  - Rapid detection and identification of overdose drugs in saliva by surface
      enhanced Raman scattering using fused gold colloids.
AB  - The number of drug-related emergency room visits in the United States doubled
      from 2004 to 2009 to 4.6 million. Consequently there is a critical need to
      rapidly identify the offending drug(s), so that the appropriate medical care can
      be administered. In an effort to meet this need we have been investigating the
      ability of surface-enhanced Raman spectroscopy (SERS) to detect and identify
      numerous drugs in saliva at ng/mL concentrations within 10 minutes.
      Identification is provided by matching measured spectra to a SERS library
      comprised of over 150 different drugs, each of which possess a unique spectrum.
      Trace detection is provided by fused gold colloids trapped within a porous glass
      matrix that generate SERS. Speed is provided by a syringe-driven sample system
      that uses a solid-phase extraction capillary combined with a SERS-active
      capillary in series. Spectral collection is provided by a portable Raman
      analyzer. Here we describe successful measurement of representative illicit,
      prescribed, and over-the-counter drugs by SERS, and 50 ng/mL cocaine in saliva as
      part of a focused study. 

PMID- 24310589
TI  - The influence of formulation and manufacturing process parameters on the
      characteristics of lyophilized orally disintegrating tablets.
AB  - Gelatin is a principal excipient used as a binder in the formulation of
      lyophilized orally disintegrating tablets. The current study focuses on
      exploiting the physicochemical properties of gelatin by varying formulation
      parameters to determine their influence on orally disintegrating tablet (ODT)
      characteristics. Process parameters, namely pH and ionic strength of the
      formulations, and ball milling were investigated to observe their effects on
      excipient characteristics and tablet formation. The properties and
      characteristics of the formulations and tablets which were investigated included:
      glass transition temperature, wettability, porosity, mechanical properties,
      disintegration time, morphology of the internal structure of the freeze-dried
      tablets, and drug dissolution. The results from the pH study revealed that
      adjusting the pH of the formulation away from the isoelectric point of gelatin,
      resulted in an improvement in tablet disintegration time possibly due to increase
      in gelatin swelling resulting in greater tablet porosity. The results from the
      ionic strength study revealed that the inclusion of sodium chloride influenced
      tablet porosity, tablet morphology and the glass transition temperature of the
      formulations. Data from the milling study showed that milling the excipients
      influenced formulation characteristics, namely wettability and powder porosity.
      The study concludes that alterations of simple parameters such as pH and salt
      concentration have a significant influence on formulation of ODT. 

PMID- 24310590
TI  - Fourth generation phosphorus-containing dendrimers: prospective drug and gene
      delivery carrier.
AB  - Research concerning new targeting delivery systems for pharmacologically active
      molecules and genetic material is of great importance. The aim of the present
      study was to investigate the potential of fourth generation (P4) cationic
      phosphorus-containing dendrimers to bind fluorescent probe 8-anilino-1
      naphthalenesulfonate (ANS), anti-neoplastic drug cisplatin, anti-HIV siRNA siP24
      and its capability to deliver green fluorescent protein gene (pGFP) into cells.
      The interaction between P4 and ANS (as the model drug) was investigated. The
      binding constant and the number of binding centers per one molecule of P4 were
      determined. In addition, the dendriplex between P4 and anti-HIV siRNA siP24 was
      characterized using circular dichroism, fluorescence polarization and zeta
      potential methods; the average hydrodynamic diameter of the dendriplex was
      calculated using zeta-size measurements. The efficiency of transfection of pGFP
      using P4 was determined in HEK293 cells and human mesenchymal stem cells, and the
      cytotoxicity of the P4-pGFP dendriplex was studied. Furthermore, enhancement of
      the toxic action of the anti-neoplastic drug cisplatin by P4 dendrimers was
      estimated. Based on the results, the fourth generation cationic phosphorus
      containing dendrimers seem to be a good drug and gene delivery carrier candidate.

PMID- 24310591
TI  - Effects of chemical and physical enhancement techniques on transdermal delivery
      of cyanocobalamin (vitamin B12) in vitro.
AB  - Vitamin B12 deficiency, which may result in anemia and nerve damage if left
      untreated, is currently treated by administration of cyanocobalamin via oral or
      intramuscular routes. However, these routes are associated with absorption and
      compliance issues which have prompted us to investigate skin as an alternative
      site of administration. Delivery through skin, however, is restricted to small
      and moderately lipophilic molecules due to the outermost barrier, the stratum
      corneum (SC). In this study, we have investigated the effect of different
      enhancement techniques, chemical enhancers (ethanol, oleic acid, propylene
      glycol), iontophoresis (anodal iontophoresis) and microneedles (soluble maltose
      microneedles), which may overcome this barrier and improve cyanocobalamin
      delivery. Studies with different chemical enhancer formulations indicated that
      ethanol and oleic acid decreased the lag time while propylene glycol based
      formulations increased the lag time. The formulation with ethanol (50%), oleic
      acid (10%) and propylene glycol (40%) showed the maximum improvement in delivery.
      Iontophoresis and microneedle treatments resulted in enhanced permeation levels
      compared to passive controls. These enhancement approaches can be explored
      further to develop alternative treatment regimens. 

PMID- 24310592
TI  - A computational procedure for assessing the dynamic performance of diffusion
      controlled transdermal delivery devices.
AB  - The dynamic performances of two different controlled-release systems were
      analyzed. In a reservoir-type drug-delivery patch, the transdermal flux is
      influenced by the properties of the membrane. A constant thermodynamic drug
      activity is preserved in the donor compartment. Monolithic matrices are among the
      most inexpensive systems used to direct drug delivery. In these structures, the
      active pharmaceutical ingredients are encapsulated within a polymeric material.
      Despite the popularity of these two devices, to tailor the properties of the
      polymer and additives to specific transient behaviors can be challenging and time
      consuming. The heuristic approaches often considered to select the vehicle
      formulation provide limited insight into key permeation mechanisms making it
      difficult to predict the device performance. In this contribution, a method to
      calculate the flux response time in a system consisting of a reservoir and a
      polymeric membrane was proposed and confirmed. Nearly 8.60 h passed before the
      metoprolol delivery rate reached ninety-eight percent of its final value. An
      expression was derived for the time it took to transport the active
      pharmaceutical ingredient out of the polymer. Ninety-eight percent of alpha
      tocopherol acetate was released in 461.4 h following application to the skin. The
      effective time constant can be computed to help develop optimum design
      strategies. 

PMID- 24310593
TI  - Effect of Penetration Enhancer Containing Vesicles on the Percutaneous Delivery
      of Quercetin through New Born Pig Skin.
AB  - Quercetin (3,3',4',5,7-pentahydroxyflavone) exerts multiple pharmacological
      effects: anti-oxidant activity, induction of apoptosis, modulation of cell cycle,
      anti-mutagenesis, and anti-inflammatory effect. In topical formulations quercetin
      inhibits oxidative skin damage and the inflammatory processes induced by solar UV
      radiation. In this work, quercetin (2 mg/mL) was loaded in vesicular Penetration
      Enhancer containing Vesicles (PEVs), prepared using a mixture of lipids
      (Phospholipon(r) 50, P50) and one of four selected hydrophilic penetration
      enhancers: Transcutol(r) P, propylene glycol, polyethylene glycol 400, and
      Labrasol(r) at the same concentration (40% of water phase). Photon Correlation
      Spectroscopy results showed a mean diameter of drug loaded vesicles in the range
      80-220 nm. All formulations showed a negative surface charge and incorporation
      efficiency in the range 48-75%. Transmission Electron Microscopy confirmed that
      size and morphology varied as a function of the used penetration enhancer. The
      influence of PEVs on ex vivo quercetin (trans)dermal delivery was evaluated using
      Franz-type diffusion cells, new born pig skin and Confocal Laser Scanning
      Microscopy. Results showed that drug delivery is affected by the penetration
      enhancer used in the PEVs' formulation. 

PMID- 24310594
TI  - Effect of microencapsulation shear stress on the structural integrity and
      biological activity of a model monoclonal antibody, trastuzumab.
AB  - The aim of the present study was to investigate the influence of process shear
      stressors on the stability of a model monoclonal antibody, trastuzumab.
      Trastuzumab, at concentrations of 0.4-4.0 mg/mL, was subjected to sonication,
      freeze-thaw, lyophilisation, spray drying and was encapsulated into micro- and
      nanoparticles. The stressed samples were analysed for structural integrity by gel
      electrophoresis, SDS-PAGE, and size exclusion chromatography (SEC), while the
      conformational integrity was analysed by circular dichroism (CD). Biological
      activity of the stressed trastuzumab was investigated by measuring the inhibition
      of cell proliferation of HER-2 expressing cell lines. Results show that
      trastuzumab was resistant to the process shear stresses applied and to
      microencapsulation processes. At the lowest concentration of 0.4 mg/mL, a low
      percent ( 0.05). The results of this study conclude that trastuzumab may be
      resistant to various processing stresses. These findings have important
      implications with respect to pharmaceutical processing of monoclonal antibodies. 

PMID- 24310595
TI  - Investigation of the atypical glass transition and recrystallization behavior of
      amorphous prazosin salts.
AB  - This manuscript studied the effect of counterion on the glass transition and
      recrystallization behavior of amorphous salts of prazosin. Three amorphous salts
      of prazosin, namely, prazosin hydrochloride, prazosin mesylate and prazosin
      tosylate were prepared by spray drying, and characterized by optical-polarized
      microscopy, differential scanning calorimetry and powder X-ray diffraction.
      Modulated differential scanning calorimetry was used to determine the glass
      transition and recrystallization temperature of amorphous salts. Glass transition
      of amorphous salts followed the order: prazosin mesylate > prazosin tosylate ~
      prazosin hydrochloride. Amorphous prazosin mesylate and prazosin tosylate showed
      glass transition, followed by recrystallization. In contrast, amorphous prazosin
      hydrochloride showed glass transition and recrystallization simultaneously.
      Density Functional Theory, however, suggested the expected order of glass
      transition as prazosin hydrochloride > prazosin mesylate > prazosin tosylate. The
      counterintuitive observation of amorphous prazosin hydrochloride having lower
      glass transition was explained in terms of its lower activation energy (206.1
      kJ/mol) for molecular mobility at Tg, compared to that for amorphous prazosin
      mesylate (448.5 kJ/mol) and prazosin tosylate (490.7 kJ/mol), and was further
      correlated to a difference in hydrogen bonding strength of the amorphous and the
      corresponding recrystallized salts. This study has implications in selection of
      an optimal amorphous salt form for pharmaceutical development. 

PMID- 24310597
TI  - Development and validation of a microbiological agar assay for determination of
      orbifloxacin in pharmaceutical preparations.
AB  - Orbifloxacin is a fluoroquinolone with broad-spectrum antimicrobial activity, and
      belongs to the third generation of quinolones. Regarding the quality control of
      medicines, a validated microbiological assay for determination of orbifloxacin in
      pharmaceutical formulations has not as yet been reported. For this purpose, this
      paper reports the development and validation of a simple, sensitive, accurate and
      reproducible agar diffusion method to quantify orbifloxacin in tablet
      formulations. The assay is based on the inhibitory effect of orbifloxacin upon
      the strain of Staphylococcus aureus ATCC 25923 used as test microorganism. The
      results were treated statistically by analysis of variance and were found to be
      linear (r = 0.9992) in the selected range of 16.0-64.0 MUg/mL, precise with
      relative standard deviation (RSD) of repeatability intraday = 2.88%, intermediate
      precision RSD = 3.33%, and accurate (100.31%). The results demonstrated the
      validity of the proposed bioassay, which allows reliable orbifloxacin
      quantitation in pharmaceutical samples and therefore can be used as a useful
      alternative methodology for the routine quality control of this medicine. 

PMID- 24310598
TI  - Application of twin screw extrusion in the manufacture of cocrystals, part I:
      four case studies.
AB  - The application of twin screw extrusion (TSE) as a scalable and green process for
      the manufacture of cocrystals was investigated. Four model cocrystal forming
      systems, Caffeine-Oxalic acid, Nicotinamide-trans cinnamic acid, Carbamazepine
      Saccharin, and Theophylline-Citric acid, were selected for the study. The
      parameters of the extrusion process that influenced cocrystal formation were
      examined. TSE was found to be an effective method to make cocrystals for all four
      systems studied. It was demonstrated that temperature and extent of mixing in the
      extruder were the primary process parameters that influenced extent of conversion
      to the cocrystal in neat TSE experiments. In addition to neat extrusion, liquid
      assisted TSE was also demonstrated for the first time as a viable process for
      making cocrystals. Notably, the use of catalytic amount of benign solvents led to
      a lowering of processing temperatures required to form the cocrystal in the
      extruder. TSE should be considered as an efficient, scalable, and environmentally
      friendly process for the manufacture of cocrystals with little to no solvent
      requirements. 

PMID- 24310596
TI  - The application of microencapsulation techniques in the treatment of endodontic
      and periodontal diseases.
AB  - In the treatment of intracanal and periodontal infections, the local application
      of antibiotics and other therapeutic agents in the root canal or in periodontal
      pockets may be a promising approach to achieve sustained drug release, high
      antimicrobial activity and low systemic side effects. Microparticles made from
      biodegradable polymers have been reported to be an effective means of delivering
      antibacterial drugs in endodontic and periodontal therapy. The aim of this review
      article is to assess recent therapeutic strategies in which biocompatible
      microparticles are used for effective management of periodontal and endodontic
      diseases. In vitro and in vivo studies that have investigated the
      biocompatibility or efficacy of certain microparticle formulations and devices
      are presented. Future directions in the application of microencapsulation
      techniques in endodontic and periodontal therapies are discussed. 

PMID- 24310599
TI  - Co-crystal screening of diclofenac.
AB  - In the pharmaceutical industry, co-crystals are becoming increasingly valuable as
      crystalline solids that can offer altered/improved physical properties of an
      active pharmaceutical ingredient (API) without changing its chemical identity or
      biological activity. In order to identify new solid forms of diclofenac-an
      analgesic with extremely poor aqueous solubility for which few co-crystal
      structures have been determined-a range of pyrazoles, pyridines, and pyrimidines
      were screened for co-crystal formation using solvent assisted grinding and
      infrared spectroscopy with an overall success rate of 50%. The crystal structures
      of three new diclofenac co-crystals are reported herein: (diclofenac)?(2
      aminopyrimidine), (diclofenac)?(2-amino-4,6-dimethylpyrimidine), and
      (diclofenac)?(2-amino-4-chloro-6-methylpyrimidine). 

PMID- 24310600
TI  - Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)
      Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2
      Inhibitors.
AB  - Photodynamic diagnosis (PDD) is a practical tool currently used in surgical
      operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a
      photon-induced physicochemical reaction which is induced by excitation of
      protoporphyrin IX (PpIX) exposed to light. Fluorescence-guided gross-total
      resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA)
      or its ester is administered as the precursor of PpIX. ALA induces the
      accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies
      provide evidence that adenosine triphosphate (ATP)-binding cassette (ABC)
      transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of
      porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein
      kinase inhibitors are suggested to potentially enhance the PDD efficacy by
      blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great
      interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain
      tumor therapy. This review article addresses a pivotal role of human ABC
      transporter ABCG2 in PDD as well as a new approach of quantitative structure
      activity relationship (QSAR) analysis to design potent ABCG2-inhibitors. 

PMID- 24310601
TI  - Structural versatility of bicellar systems and their possibilities as colloidal
      carriers.
AB  - Bicellar systems are lipid nanostructures formed by long- and short-chained
      phospholipids dispersed in aqueous solution. The morphological transitions of
      bicellar aggregates due to temperature, composition and time variations have been
      revised in this work. To this end, two bicellar systems have been considered; one
      formed by dimyristoyl-phosphatidylcholine (DMPC) and dihexanoyl-
      phosphatidylcholine (DHPC) and another formed by dipalmitoyl-phosphatidylcholine
      (DPPC) and DHPC. The relationship between the magnetic alignment, the morphology
      of the aggregates and the phase transition temperature (Tm) of lipids is
      discussed. In general terms, the non-alignable samples present rounded objects at
      temperature below the Tm. Above this temperature, an increase of viscosity is
      followed by the formation of large elongated aggregates. Alignable samples
      presented discoidal objects below the Tm. The best alignment was achieved above
      this temperature with large areas of lamellar stacked bilayers and some
      multilamellar vesicles. The effect of the inclusion of ceramides with different
      chain lengths in the structure of bicelles is also revised in the present
      article. A number of physical techniques show that the bicellar structures are
      affected by both the concentration and the type of ceramide. Systems are able to
      incorporate 10% mol of ceramides that probably are organized forming domains. The
      addition of 20% mol of ceramides promotes destabilization of bicelles, promoting
      the formation of mixed systems that include large structures. Bicellar systems
      have demonstrated to be morphologically stable with time, able to encapsulate
      different actives and to induce specific effects on the skin. These facts make
      bicellar systems good candidates as colloidal carriers for dermal delivery.
      However, water dilution induces structural changes and formation of vesicular
      structures in the systems; stabilization strategies have been been explored in
      recent works and are also updated here. 

PMID- 24310602
TI  - Development of a valid simplified Chinese version of the Oxford Hip Score in
      patients with hip osteoarthritis.
AB  - BACKGROUND: Although the Oxford Hip Score has been translated and validated in
      several languages, there is currently no Chinese version of the outcomes
      measurement. Our study aims to crossculturally adapt and validate the Oxford Hip
      Score into a simplified Chinese version. QUESTIONS/PURPOSES: We tested the (1)
      reliability; (2) validity; and (3) responsiveness of the Chinese version of the
      Oxford Hip Score. METHODS: First we translated the Oxford Hip Score into
      simplified Chinese, then back into English, then held a consensus meeting to
      achieve the final simplified Chinese version. Then we evaluated the psychometric
      properties of Chinese version of the Oxford Hip Score in patients undergoing
      total hip arthroplasty (THA). All patients undergoing THA between July and
      December 2012 were invited to participate in this study; a total of 108 (79% of
      136 invited) did so. To assess the test-retest validity, all participants
      completed the Chinese version of the Oxford Hip Score again with a 2-week
      interval. Pearson correlation coefficient was used to evaluate the construct
      validity between the Chinese version of the Oxford Hip Score and visual analog
      scale (VAS), Harris hip score, and eight individual domains of the SF-36.
      Responsiveness was demonstrated by comparing the pre- and postoperative scores of
      the Chinese version of the Oxford Hip Score. RESULTS: The test-retest reliability
      with intraclass correlation coefficient (0.937) and internal consistency with
      Cronbach's alpha (0.91) were excellent. The Chinese version of the Oxford Hip
      Score correlated with the Harris hip score (0.89, p < 0.01), VAS (-0.79, p <
      0.01), and Physical Functioning (0.79, p < 0.01) and Bodily Pain (0.70, p < 0.01)
      domains of SF-36, which suggested construct validity. No floor or ceiling effects
      were found. The effect size and standardized response mean values were 3.52 and
      3.31, respectively, indicating good responsiveness. CONCLUSIONS: The Chinese
      version of the Oxford Hip Score showed good reliability, validity, and
      responsiveness in evaluating standard Chinese-speaking patients with hip
      osteoarthritis undergoing THA. It can be used by clinical surgeons as a
      complement to the traditional outcome measures.

PMID- 24310603
TI  - Tardive dyskinesia: therapeutic options for an increasingly common disorder.
AB  - Tardive dyskinesia (TD) is a serious, often disabling, movement disorder that is
      caused by medications that block dopamine receptors (i.e., neuroleptics, anti
      emetics). There is currently no standard treatment approach for physicians
      confronted with such patients. This may be the result of notions that TD is
      disappearing because of the switch to second-generation antipsychotic agents and
      that it is largely reversible. In this article we demonstrate that second
      generation antipsychotics do, indeed, cause TD and, in fact, the frequency is
      likely higher than expected because of growing off-label uses and a tripling of
      prescriptions written in the last 10 years. In addition, studies demonstrate that
      TD actually remits in only a minority of patients when these drugs are withdrawn.
      Furthermore, neuroleptic agents are often utilized to treat TD, despite prolonged
      exposure being a risk factor for irreversibility. The outcome of these trends is
      a growing population afflicted with TD. We review non-neuroleptic agents that
      have shown positive results in small, early-phase, blinded trials, including
      tetrabenazine, amantadine, levetiracetam, piracetam, clonazepam, propranolol,
      vitamin B6, and Ginkgo biloba. Other options, such as botulinum toxin and deep
      brain stimulation, will also be discussed, and a suggested treatment algorithm is
      provided. While these agents are reasonable treatment options at this time there
      is a need, with a concerted effort between neurology and psychiatry, for full
      scale drug development, including multicenter, randomized, blinded trials to
      confirm the effectiveness of the agents that were positive in phase 2 trials and
      the development of newer ones.

PMID- 24310605
TI  - Investigation of the functional expression of purine and pyrimidine receptors in
      porcine isolated pancreatic arteries.
AB  - Receptors for purines and pyrimidines are expressed throughout the cardiovascular
      system. This study investigated their functional expression in porcine isolated
      pancreatic arteries. Pancreatic arteries (endothelium intact or denuded) were
      prepared for isometric tension recording and preconstricted with U46619, a
      thromboxane A(2) mimetic; adenosine-5'-diphosphate (ADP), uridine-5'-triphosphate
      (UTP) and MRS2768, a selective P2Y(2) agonist, were applied cumulatively, while
      adenosine-5'-triphosphate (ATP) and alphabeta-methylene-ATP (alphabeta-meATP)
      response curves were generated from single concentrations per tissue segment.
      Antagonists/enzyme inhibitors were applied prior to U46619 addition. ATP,
      alphabeta-meATP, UTP and MRS2768 induced vasoconstriction, with a potency order
      of alphabeta-meATP > MRS2768 > ATP >= UTP. Contractions to ATP and alphabeta
      meATP were blocked by NF449, a selective P2X(1) receptor antagonist. The
      contraction induced by ATP, but not UTP, was followed by vasorelaxation.
      Endothelium removal and DUP 697, a cyclooxygenase-2 inhibitor, had no significant
      effect on contraction to ATP but attenuated that to UTP, indicating actions at
      distinct receptors. MRS2578, a selective P2Y(6) receptor antagonist, had no
      effect on contractions to UTP. ADP induced endothelium-dependent vasorelaxation
      which was inhibited by MRS2179, a selective P2Y(1) receptor antagonist, or
      SCH58261, a selective adenosine A(2A) receptor antagonist. The contractions to
      ATP and alphabeta-meATP were attributed to actions at P2X(1) receptors on the
      vascular smooth muscle, whereas it was shown for the first time that UTP induced
      an endothelium-dependent vasoconstriction which may involve P2Y(2) and/or P2Y(4)
      receptors. The relaxation induced by ADP is mediated by P2Y(1) and A(2A)
      adenosine receptors. Porcine pancreatic arteries appear to lack vasorelaxant
      P2Y(2) and P2Y(4) receptors.

PMID- 24310604
TI  - Treatment of Parkinson's disease: what's in the non-dopaminergic pipeline?
AB  - Dopamine depletion resulting from degeneration of nigrostriatal dopaminergic
      neurons is the primary neurochemical basis of the motor symptoms of Parkinson's
      disease (PD). While dopaminergic replacement strategies are effective in
      ameliorating these symptoms early in the disease process, more advanced stages of
      PD are associated with the development of treatment-related motor complications
      and dopamine-resistant symptoms. Other neurotransmitter and neuromodulator
      systems are expressed in the basal ganglia and contribute to the extrapyramidal
      refinement of motor function. Furthermore, neuropathological studies suggest that
      they are also affected by the neurodegenerative process. These non-dopaminergic
      systems provide potential targets for treatment of motor fluctuations, levodopa
      induced dyskinesias, and difficulty with gait and balance. This review summarizes
      recent advances in the clinical development of novel pharmacological approaches
      for treatment of PD motor symptoms. Although the non-dopaminergic pipeline has
      been slow to yield new drugs, further development will likely result in improved
      treatments for PD symptoms that are induced by or resistant to dopamine
      replacement. 

PMID- 24310606
TI  - NT5E and FcGBP as key regulators of TGF-1-induced epithelial-mesenchymal
      transition (EMT) are associated with tumor progression and survival of patients
      with gallbladder cancer.
AB  - Epithelial-mesenchymal transitions (EMTs) are essential manifestations of
      epithelial cell plasticity during tumor progression. Transforming growth factor
      beta(TGF-beta) modulates epithelial plasticity in tumor physiological contexts by
      inducing EMT, which is associated with the altered expression of genes. In the
      present study, we used DNA micro-array analysis to search for differentially
      expressed genes in the TGF-beta1 induced gallbladder carcinoma cell line (GBC-SD
      cells), as compared with normal GBC-SD cells. We identified 225 differentially
      expressed genes, including 144 that were over-expressed and 81 that were under
      expressed in the TGF-beta1 induced GBC-SD cells. NT5E (CD73) is the most
      increased gene, while the Fc fragment of the IgG binding protein (FcGBP) is the
      most decreased gene. The expression patterns of these two genes in gallbladder
      adenocarcinoma and chronic cholecystitis tissue were consistent with the micro
      array data. Immunochemistry and clinicopathological results showed that the
      expression of NT5E and FcGBP in gallbladder adenocarcinoma is an independent
      marker for evaluation of the disease progression, clinical biological behaviors
      and prognosis. The data from the current study indicate that differential NT5E
      and FcGBP expressions could be further evaluated as biomarkers for predicting
      survival of patients with gallbladder cancer and that NT5E and FcGBP could be
      promising targets in the control of gallbladder cancer progression. 

PMID- 24310607
TI  - Morphological and cellular examinations of experimentally induced malocclusion in
      mice mandibular condyle.
AB  - Occlusal alignment is known clinically to have a widespread influence on the
      stomatognathic system, including the temporomandibular joint and masticatory
      muscles. However, while occlusion is still an important determinant of most
      dental treatments, the exact effect of occlusal alignment is unclear because of a
      lack of conclusive scientific evidence. In this study, a malocclusion model
      system is used to examine the cellular and histologic alterations in the
      contralateral condyle of mice after a malocclusion was induced by a build-up of
      resin on the left maxillary molars. A significant decrease in the thickness of
      the condylar cartilage was found in the 1-week experimental group, together with
      increased apoptosis and decreased proliferation in the condylar head, which
      included cartilage and subchondral bone. Additionally, the number of TRAP
      positive osteoclasts and MPO- and F4/80-positive inflammatory cells in the
      subchondral bone were significantly higher in the 1-week experimental group.
      Unbalanced malocclusion caused increased bone remodeling, as evidenced by
      increased osteoclastic activity and inflammatory responses (macrophages and
      neutrophils, respectively). However, these alterations in the 1-week experimental
      group were subsequently attenuated and restored almost to the baseline at 3 weeks
      after the induction of the malocclusion.

PMID- 24310609
TI  - Tunable electrical conductivity in metal-organic framework thin-film devices.
AB  - We report a strategy for realizing tunable electrical conductivity in metal
      organic frameworks (MOFs) in which the nanopores are infiltrated with redox
      active, conjugated guest molecules. This approach is demonstrated using thin-film
      devices of the MOF Cu3(BTC)2 (also known as HKUST-1; BTC, benzene-1,3,5
      tricarboxylic acid) infiltrated with the molecule 7,7,8,8
      tetracyanoquinododimethane (TCNQ). Tunable, air-stable electrical conductivity
      over six orders of magnitude is achieved, with values as high as 7 siemens per
      meter. Spectroscopic data and first-principles modeling suggest that the
      conductivity arises from TCNQ guest molecules bridging the binuclear copper
      paddlewheels in the framework, leading to strong electronic coupling between the
      dimeric Cu subunits. These ohmically conducting porous MOFs could have
      applications in conformal electronic devices, reconfigurable electronics, and
      sensors. 

PMID- 24310608
TI  - Association of the autoimmune disease scleroderma with an immunologic response to
      cancer.
AB  - Autoimmune diseases are thought to be initiated by exposures to foreign antigens
      that cross-react with endogenous molecules. Scleroderma is an autoimmune
      connective tissue disease in which patients make antibodies to a limited group of
      autoantigens, including RPC1, encoded by the POLR3A gene. As patients with
      scleroderma and antibodies against RPC1 are at increased risk for cancer, we
      hypothesized that the "foreign" antigens in this autoimmune disease are encoded
      by somatically mutated genes in the patients' incipient cancers. Studying cancers
      from scleroderma patients, we found genetic alterations of the POLR3A locus in
      six of eight patients with antibodies to RPC1 but not in eight patients without
      antibodies to RPC1. Analyses of peripheral blood lymphocytes and serum suggested
      that POLR3A mutations triggered cellular immunity and cross-reactive humoral
      immune responses. These results offer insight into the pathogenesis of
      scleroderma and provide support for the idea that acquired immunity helps to
      control naturally occurring cancers. 

PMID- 24310610
TI  - Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances
      antigen presentation.
AB  - The yellow fever vaccine YF-17D is one of the most successful vaccines ever
      developed in humans. Despite its efficacy and widespread use in more than 600
      million people, the mechanisms by which it stimulates protective immunity remain
      poorly understood. Recent studies using systems biology approaches in humans have
      revealed that YF-17D-induced early expression of general control nonderepressible
      2 kinase (GCN2) in the blood strongly correlates with the magnitude of the later
      CD8(+) T cell response. We demonstrate a key role for virus-induced GCN2
      activation in programming dendritic cells to initiate autophagy and enhanced
      antigen presentation to both CD4(+) and CD8(+) T cells. These results reveal an
      unappreciated link between virus-induced integrated stress response in dendritic
      cells and the adaptive immune response. 

PMID- 24310611
TI  - Break-induced replication repair of damaged forks induces genomic duplications in
      human cells.
AB  - In budding yeast, one-ended DNA double-strand breaks (DSBs) and damaged
      replication forks are repaired by break-induced replication (BIR), a homologous
      recombination pathway that requires the Pol32 subunit of DNA polymerase delta.
      DNA replication stress is prevalent in cancer, but BIR has not been characterized
      in mammals. In a cyclin E overexpression model of DNA replication stress, POLD3,
      the human ortholog of POL32, was required for cell cycle progression and
      processive DNA synthesis. Segmental genomic duplications induced by cyclin E
      overexpression were also dependent on POLD3, as were BIR-mediated recombination
      events captured with a specialized DSB repair assay. We propose that BIR repairs
      damaged replication forks in mammals, accounting for the high frequency of
      genomic duplications in human cancers. 

PMID- 24310613
TI  - Radioactive cesium accumulation in seaweeds by the Fukushima 1 Nuclear Power
      Plant accident-two years' monitoring at Iwaki and its vicinity.
AB  - Accumulations of radionuclides in marine macroalgae (seaweeds) resulting from the
      Fukushima 1 Nuclear Power Plant (F1NPP) accident in March 2011 have been
      monitored for two years using high-purity germanium detectors. Algal specimens
      were collected seasonally by snorkeling at Nagasaki, Iwaki, Fukushima Prefecture
      (Pref.), Japan, ca. 50 km perimeter from the F1NPP. Additional collections were
      done at Soma, Hironocho, Hisanohama and Shioyazaki in Fukushima Pref. as well as
      at Chiba Pref. and Hyogo Pref. as controls. In May 2011, specimens of most
      macroalgal species showed 137Cs levels greater than 3,000 Bq kg-1 at Shioyazaki
      and Nagasaki. The highest 137Cs level recorded 7371.20 +/- 173.95 Bq kg-1 in
      Undaria pinnatifida (Harvey) Suringar on 2 May 2011, whereas seawater collected
      at the same time at Shioyazaki and Nagasaki measured 8.41 +/- 3.21 and 9.74 +/-
      3.43 Bq L-1, respectively. The concentration factor of marine macroalgae was
      estimated to be ca. 8-50, depending on taxa and considering a weight ratio of
      wet/dry samples of ca. 10. 137Cs level declined remarkably during the following 5
      6 months. In contrast, the 137Cs level remained rather stable during the
      following 12-16 months, and maintained the range of 10-110 Bq kg-1. Contamination
      was still detectable in many samples in March 2013, 24 months after the most
      significant pollution.

PMID- 24310612
TI  - Targeted therapy resistance mediated by dynamic regulation of extrachromosomal
      mutant EGFR DNA.
AB  - Intratumoral heterogeneity contributes to cancer drug resistance, but the
      underlying mechanisms are not understood. Single-cell analyses of patient-derived
      models and clinical samples from glioblastoma patients treated with epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that
      tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring
      distinct cellular phenotypes to reach an optimal equilibrium for growth.
      Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from
      extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations
      on extrachromosomal DNA follows. These results indicate a highly specific,
      dynamic, and adaptive route by which cancers can evade therapies that target
      oncogenes maintained on extrachromosomal DNA. 

PMID- 24310614
TI  - Growth, allometry and shade tolerance of understory saplings of four subalpine
      conifers in central Japan.
AB  - The conifers Abies veitchii, A. mariesii, Picea jezoensis var. hondoensis, Tsuga
      diversifolia dominate in subalpine forests in central Japan. We expected that
      species differences in shade tolerance and in aboveground and belowground
      architecture are important for their coexistence. We examined net production and
      carbon allocation of understory saplings. Although the four species allocated
      similar amounts of biomass to roots at a given trunk height, the root-zone area
      of T. diversifolia was greater than that of the three other species. T.
      diversifolia often dominates shallow soil sites, such as ridge and rocky slopes,
      and, therefore, a wide spread of lateral roots would be an adaptation to such
      edaphic conditions. Crown width and leaf and branch mass were greatest for T.
      diversifolia and A. mariesii, followed in order by A. veitchii and P. jezoensis
      var. hondoensis. Although leaf mass of P. jezoensis var. hondoensis was lowest
      among the four species, species differences were not found in the net production
      per sapling because net production per leaf mass was greatest for P. jezoensis
      var. hondoensis. The leaf lifespan was longer in the order A. mariesii, T.
      diversifolia, P. jezoensis var. hondoensis and A. veitchii. The minimum rate of
      net production per leaf mass required to maintain the current sapling leaf mass
      (MRNP(LM)) was lowest in A. mariesii and T. diversifolia, and increased in the
      order of A. veitchii and P. jezoensis var. hondoensis. A. mariesii and T.
      diversifolia may survive in shade conditions by a lower MRNP(LM) than the two
      other species. Therefore, species differences in aboveground and belowground
      architecture and MRNPLM reflected their shade tolerance and regeneration
      strategies, which contribute to their coexistence.

PMID- 24310615
TI  - First flowering hybrid between autotrophic and mycoheterotrophic plant species:
      breakthrough in molecular biology of mycoheterotrophy.
AB  - Among land plants, which generally exhibit autotrophy through photosynthesis,
      about 880 species are mycoheterotrophs, dependent on mycorrhizal fungi for their
      carbon supply. Shifts in nutritional mode from autotrophy to mycoheterotrophy are
      usually accompanied by evolution of various combinations of characters related to
      structure and physiology, e.g., loss of foliage leaves and roots, reduction in
      seed size, degradation of plastid genome, and changes in mycorrhizal association
      and pollination strategy. However, the patterns and processes involved in such
      alterations are generally unknown. Hybrids between autotrophic and
      mycoheterotrophic plants may provide a breakthrough in molecular studies on the
      evolution of mycoheterotrophy. We have produced the first hybrid between
      autotrophic and mycoheterotrophic plant species using the orchid group Cymbidium.
      The autotrophic Cymbidium ensifolium subsp. haematodes and mycoheterotrophic C.
      macrorhizon were artificially pollinated, and aseptic germination of the hybrid
      seeds obtained was promoted by sonication. In vitro flowering was observed five
      years after seed sowing. Development of foliage leaves, an important character
      for photosynthesis, segregated in the first generation; that is, some individuals
      only developed scale leaves on the rhizome and flowering stems. However, all of
      the flowering plants formed roots, which is identical to the maternal parent. 

PMID- 24310617
TI  - X-ray doses from radar received by Belgian professional military radar operators.

PMID- 24310616
TI  - Prevalence of the HOXB13 G84E mutation among unaffected men with a family history
      of prostate cancer.
AB  - HOXB13 (G84E) was reported to significantly increase risk for prostate cancer.
      The goal of the current analysis was to assess the prevalence of G84E in
      ethnically-diverse high-risk men undergoing prostate cancer screening and place
      the carrier frequency within the context of prevalence estimates from reported
      studies to gain insight into the future role of this mutation in genetic
      counseling. PRAP is a prostate cancer screening program for unaffected men ages
      35-69 with a family history of prostate cancer or African descent. HOXB13 G84E
      was genotyped by pyrosequencing in 649 PRAP participants with available DNA.
      Prevalence of the mutation was calculated for PRAP and for reported studies and
      exact binomial confidence intervals were generated. Prevalence of the G84E
      mutation in non-African PRAP men was 0.73 %. When placed in context of the
      literature, this was higher than reported controls. One G84E mutation carrier was
      notably of Hispanic background. While the HOXB13 G84E mutation may be rare, there
      may be a future role in genetic testing for this mutation after further studies
      of clinical utility in assessing prostate cancer risk. 

PMID- 24310618
TI  - Hospital utilization, costs and mortality rates during the first 5 years of life:
      a population study of ART and non-ART singletons.
AB  - STUDY QUESTION: Do singletons conceived following assisted reproduction
      technologies (ARTs) have significantly different hospital utilization, and
      therefore costs, compared with non-ART children during the first 5 years of life?
      SUMMARY ANSWER: ART singletons have longer hospital birth-admissions and a small
      increased risk of re-admission during the first 5 years of life resulting in
      higher costs of hospital care. WHAT IS KNOWN ALREADY: ART singletons are at
      greater risk of adverse perinatal outcomes compared with non-ART singletons. Long
      term physical and mental health outcomes of ART singletons are generally
      reassuring. There is a scarcity of information on health service utilization and
      the health economic impact of ART conceived children. STUDY DESIGN, SIZE,
      DURATION: A population cohort study using linked birth, hospital and death
      records. Perinatal outcomes, hospital utilization and costs, and mortality rates
      were compared for non-ART and ART singletons to 5 years. Adjustments were made
      for maternal age, parity, sex, birth year, socioeconomic status and funding
      source. Australian Diagnosis Related Groups cost-weights were used to derive
      costs. All costs are reported in 2009/2010 Australian dollars.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: All babies born in Western Australia
      between 1994 and 2003 were included; 224 425 non-ART singletons and 2199 ART
      conceived singletons. Hospital admission and death records in Western Australia
      linked to 2008 were used. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, ART
      singletons had a significantly longer length of stay during the birth-admission
      (mean difference 1.8 days, P < 0.001) and a 20% increased risk of being admitted
      during the first 5 years of life. The average adjusted difference in hospital
      admission costs up to 5 years of age was $2490, with most of the additional cost
      occurring during the birth-admission ($1473). The independent residual cost
      associated with ART conception was $342 during the birth-admission and an
      additional $548 up to 5 years of age, indicating that being conceived as an ART
      child predicts not only higher birth-admission costs but excess costs to at least
      5 years of age. LIMITATIONS, REASONS FOR CAUTION: This study could not
      investigate the impact of different ART practices and techniques on perinatal
      outcomes or hospital utilization, nor could it adjust for parental
      characteristics such as cause of infertility and treatment-seeking behaviour.
      This study related to ART treatment undertaken before 2003. WIDER IMPLICATIONS OF
      THE FINDINGS: Clinicians and patients should be aware of the risk of poorer
      perinatal outcomes and increased hospitalization of ART singletons compared with
      non-ART singletons. These differences are significant enough to affect health
      care resource consumption, but are substantially and significantly less than
      those associated with ART multiple birth infants. Understanding the short- and
      long-term health services and economic impact of ART is important for setting the
      research agenda in ART, for informing economic evaluations of infertility and
      treatment strategies, and for providing an important input to clinical and
      administrative decision making. STUDY FUNDING/COMPETING INTEREST(S): No specific
      funding was used to undertake this study and the authors report no conflicts of
      interest. A number of the authors receive Research Grants to their institutions
      from the Australian Government. G.M.C. receives grant support to her institution
      from the Australian Government, Australian Research Council (ARC) Linkage Grant
      No LP1002165; ARC Linkage Grant Partner Organisations are IVFAustralia, Melbourne
      IVF and Queensland Fertility Group. V.P.H. is employed as an Economics Research
      Associate on the same grant. TRIAL REGISTRATIONS NUMBER: NA.

PMID- 24310620
TI  - Selective synthesis of [7]- and [8]cycloparaphenylenes.
AB  - Cycloparaphenylenes (CPPs) are a remarkable class of hoop-shaped conjugated
      macrocycles with inimitable properties. Herein we describe a divergent synthesis
      of [7]CPP and [8]CPP. Furthermore we present the first crystal structure of
      [7]CPP. Thus, we have now established the size-selective synthesis of [n]CPP (n =
      7-16) in a uniformed cyclohexane-based method. 

PMID- 24310619
TI  - KNL1: bringing order to the kinetochore.
AB  - KNL1 is an evolutionarily conserved kinetochore-associated protein essential for
      accurate chromosome segregation in eukaryotic cells. This large scaffold protein,
      predicted to be almost entirely unstructured, is involved in diverse mitotic
      processes including kinetochore assembly, chromosome congression, and mitotic
      checkpoint signaling. How this kinetochore "hub" coordinates protein-protein
      interactions spatially and temporally during mitosis to orchestrate these
      processes is an area of active investigation. Here we summarize the current
      understanding of KNL1 and discuss possible mechanisms by which this protein
      actively contributes to multiple aspects of mitotic progression. 

PMID- 24310622
TI  - Phototoxic effects of an operating microscope on the ocular surface and tear
      film.
AB  - PURPOSE: We evaluated light exposure-induced dry eye syndrome by investigating
      the phototoxic effects of an operating microscope on the ocular surface and tear
      film in rabbits. METHODS: Sixty eyes of 30 rabbits were divided into 3 groups
      based on the intensity of light exposure received from an operating microscope:
      Control group, no exposure to light; group A, 40,000-lx intensity for 30 minutes;
      and group B, 100,000-lx intensity for 30 minutes. To evaluate the potential
      damage to the ocular surface and tear film, Schirmer tests, rose bengal staining,
      and conjunctival impression cytology were performed before the light exposure and
      at 1, 3, and 5 days afterward. In addition, the expression of interleukin 1-beta
      was analyzed in tear samples. The expression of mucin 5AC was evaluated using
      immunofluorescence staining, and periodic acid-Schiff staining was conducted on
      conjunctival tissues. Corneal and conjunctival tissues were observed by means of
      electron microscopy. RESULTS: Potential damage to the ocular surface and tear
      film was found in the light-exposed groups as evidenced by decreased aqueous tear
      production, devitalized corneal and conjunctival epithelial cells, squamous
      metaplasia of conjunctival epithelial cells, decreased conjunctival goblet cell
      density, decreased expression of mucin 5AC, ultrastructural cellular damage to
      corneal and conjunctival tissues, and increased interleukin 1-beta expression in
      tears. This damage was more noticeable in group B than in group A (P < 0.05).
      CONCLUSIONS: Light exposure from an operating microscope had phototoxic effects
      on the ocular surface and tear film in this in vivo experiment. These changes
      seemed to intensify as the intensity of the light increased. Therefore, excessive
      light exposure during ophthalmic procedures could be a pathogenic factor in dry
      eye syndrome after a surgery is performed.

PMID- 24310623
TI  - The role of extracellular matrix in corneal wound healing. Cornea 2013;32(suppl):
      s43-s45-retracted.

PMID- 24310621
TI  - Bisphosphonamidate clodronate prodrug exhibits selective cytotoxic activity
      against melanoma cell lines.
AB  - Bisphosphonates are used clinically to treat disorders of calcium metabolism and
      malignant bone disease and are known to inhibit cancer cell growth, adhesion, and
      invasion. However, clinical use of these agents for the treatment of
      extraskeletal disease is limited because of low cell permeability. We recently
      described a bisphosphonamidate prodrug strategy for efficient intracellular
      release of bisphosphonates, including clodronate (CLO), in non-small cell lung
      cancer cells. To evaluate anticancer activity of this prodrug class across many
      cancer cell types, the bisphosphonamidate clodronate prodrug (CLO prodrug) was
      screened against the NCI-60 cell line panel, and was found to exhibit selectivity
      toward melanoma cell lines. Here, we confirm efficient cellular uptake and
      intracellular activation of this prodrug class in melanoma cells. We further
      demonstrate inhibition of melanoma cell proliferation, induction of apoptosis,
      and an antitumor effect of CLO prodrug in a xenograft model. These data suggest a
      novel therapeutic application for the CLO prodrug and potential to selectively
      target melanoma cells.

PMID- 24310624
TI  - The Brazilian Journal of Pulmonology and international databases.

PMID- 24310625
TI  - Level of asthma control and its impact on activities of daily living in asthma
      patients in Brazil.
AB  - OBJECTIVE: To evaluate the impact of asthma on activities of daily living and on
      health status in patients with controlled, partially controlled, or uncontrolled
      asthma in Brazil. METHODS: We used data related to 400 patients in four Brazilian
      cities (Sao Paulo, Rio de Janeiro, Salvador, and Curitiba), obtained in a survey
      conducted throughout Latin America in 2011. All study subjects were > 12 years of
      age and completed a standardized questionnaire in face-to-face interviews. The
      questions addressed asthma control, hospitalizations, emergency room visits, and
      school/work absenteeism, as well as the impact of asthma on the quality of life,
      sleep, and leisure. The level of asthma control was determined in accordance with
      the Global Initiative for Asthma criteria. RESULTS: Among the 400 respondents,
      asthma was controlled in 37 (9.3%), partially controlled in 226 (56.5%), and
      uncontrolled in 137 (34.2%). The numbers of patients with uncontrolled or
      partially controlled asthma who visited the emergency room, who were
      hospitalized, and who missed school/work were higher than were those of patients
      with controlled asthma (p = 0.001, p = 0.05, and p = 0.01, respectively). Among
      those with uncontrolled asthma, the impact of the disease on activities of daily
      living, sleep, social activities, and normal physical exertion was greater than
      it was among those with controlled or partially controlled asthma (p < 0.001).
      CONCLUSIONS: In Brazil, asthma treatment should be monitored more closely in
      order to increase treatment adherence and, consequently, the level of asthma
      control, which can improve patient quality of life and minimize the negative
      impact of the disease.

PMID- 24310626
TI  - Delayed diagnosis of sarcoidosis is common in Brazil.
AB  - OBJECTIVE: To determine the frequency of and the factors related to delayed
      diagnosis of sarcoidosis in Brazil. METHODS: We evaluated patients with a biopsy
      proven diagnosis of sarcoidosis, using a questionnaire that addressed the
      following: time since symptom onset and since the first medical visit; and the
      number and specialty of the physicians visited. We divided the patients by the
      timeliness of the diagnosis-timely (< 6 months) and delayed (>= 6 months)
      comparing the two groups in terms of systemic and pulmonary symptoms;
      extrathoracic involvement; spirometric data; radiological staging; level of
      education; income; and tuberculosis (diagnosis and treatment). RESULTS: We
      evaluated 100 patients. The median number of physicians consulted was 3 (range, 1
      14). In 11 cases, sarcoidosis was diagnosed at the first visit. In 54, the first
      physician seen was a general practitioner. The diagnosis of sarcoidosis was
      timely in 41 patients and delayed in 59. The groups did not differ in terms of
      gender; race; type of health insurance; level of education; income;
      respiratory/systemic symptoms; extrathoracic involvement; and radiological
      staging. In the delayed diagnosis group, FVC was lower (80.3 +/- 20.4% vs. 90.5
      +/- 17.1%; p = 0.010), as was FEV1 (77.3 +/- 19.9% vs. 86.4 +/- 19.5%; p =
      0.024), misdiagnosis with and treatment for tuberculosis (>= 3 months) also being
      more common (24% vs. 7%, p = 0.032, and 20% vs. 0%; p = 0.002, respectively).
      CONCLUSIONS: The diagnosis of sarcoidosis is often delayed, even when the imaging
      is suggestive of sarcoidosis. Delayed diagnosis is associated with impaired lung
      function at the time of diagnosis. Many sarcoidosis patients are misdiagnosed
      with and treated for tuberculosis.

PMID- 24310627
TI  - Validation and development of an immunonephelometric assay for the determination
      of alpha-1 antitrypsin levels in dried blood spots from patients with COPD.
AB  - OBJECTIVE: To validate and develop an immunonephelometric assay for the
      determination of alpha-1 antitrypsin (AAT) levels in dried blood spots from COPD
      patients in Brazil. METHODS: We determined AAT levels in serum samples and dried
      blood spots from 192 COPD patients. For the preparation of dried blood spots, a
      disk (diameter, 6 mm) was placed into a tube, eluted with 200 uL of PBS, and
      stored overnight at 4oC. All of the samples were analyzed by immunonephelometry
      in duplicate. We used the bootstrap resampling method in order to determine a cut
      off point for AAT levels in dried blood spots. RESULTS: The correlation
      coefficient between the AAT levels in serum samples and those in dried blood
      spots was r = 0.45. For dried blood spots, the cut-off value was 2.02 mg/dL (97%
      CI: 1.45-2.64 mg/dL), with a sensitivity, specificity, positive predictive value,
      and negative predictive value of 100%, 95.7%, 27.2%, and 100%, respectively.
      CONCLUSIONS: This method for the determination of AAT levels in dried blood spots
      appears to be a reliable screening tool for patients with AAT deficiency.

PMID- 24310628
TI  - Cystic fibrosis transmembrane conductance regulator mutations at a referral
      center for cystic fibrosis.
AB  - OBJECTIVE: To determine the frequency of six mutations (F508del, G542X, G551D,
      R553X, R1162X, and N1303K) in patients with cystic fibrosis (CF) diagnosed, at a
      referral center, on the basis of abnormal results in two determinations of sweat
      sodium and chloride concentrations. METHODS: This was a cross-sectional study
      involving 70 patients with CF. The mean age of the patients was 12.38 +/- 9.00
      years, 51.43% were female, and 94.29% were White. Mutation screening was
      performed with polymerase chain reaction (for F508del), followed by enzymatic
      digestion (for other mutations). Clinical analysis was performed on the basis of
      gender, age, ethnicity, pulmonary/gastrointestinal symptoms, and Shwachman
      Kulczycki (SK) score. RESULTS: All of the patients showed pulmonary symptoms, and
      8 had no gastrointestinal symptoms. On the basis of the SK scores, CF was
      determined to be mild, moderate, and severe in 22 (42.3%), 17 (32.7%), and 13
      (25.0%) of the patients, respectively. There was no association between F508del
      mutation and disease severity by SK score. Of the 140 alleles analyzed, F508del
      mutation was identified in 70 (50%). Other mutations (G542X, G551D, R553X,
      R1162X, and N1303K) were identified in 12 (7.93%) of the alleles studied. In
      F508del homozygous patients with severe disease, the OR was 0.124 (95% CI: 0.005
      0.826). CONCLUSIONS: In 50% of the alleles studied, the molecular diagnosis of CF
      was confirmed by identifying a single mutation (F508del). If we consider the
      analysis of the six most common mutations in the Brazilian population (including
      F508del), the molecular diagnosis was confirmed in 58.57% of the alleles studied.

PMID- 24310629
TI  - The influence of leptin on Th1/Th2 balance in obese children with asthma.
AB  - OBJECTIVE: In individuals with asthma, obesity induces the production of leptin
      and is associated with disease severity. Our objective was to evaluate the levels
      of serum leptin and their effect on Th1/Th2 balance in obese and non-obese
      children with asthma, as well as to investigate the association between serum
      leptin levels and clinical outcomes. METHODS: We evaluated 50 atopic children
      with physician-diagnosed moderate-to-severe persistent asthma and 20 controls.
      The children with asthma were divided into two groups, by body mass index
      percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we
      collected peripheral blood samples in order to determine the levels of leptin,
      IFN-gamma, and IL-4. Asthma severity was assessed by an asthma symptom score, and
      the results were correlated with the parameters studied. RESULTS: Serum leptin
      levels were significantly higher in the obese asthma group than in the non-obese
      asthma group, as well as being significantly higher in the children with asthma
      than in the controls, whereas IFN-gamma levels were significantly higher and IL-4
      levels were significantly lower in the obese asthma group than in the non-obese
      asthma group. In addition, the obese asthma group showed higher asthma symptom
      scores and significantly lower FEV1 (% of predicted) than did the non-obese
      asthma group. There was a significant positive correlation between leptin and IFN
      gamma levels only in the obese asthma group. CONCLUSIONS: Although leptin is
      involved in the pathogenesis of asthma in obese and non-obese children, its
      effect is more pronounced in the former. In the presence of high leptin levels,
      only obese children with asthma exhibited Th1 polarization, with higher IFN-gamma
      levels and greater asthma severity.

PMID- 24310630
TI  - Diagnostic criteria and follow-up in neuroendocrine cell hyperplasia of infancy:
      a case series.
AB  - OBJECTIVE: Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of
      childhood interstitial lung disease characterized by tachypnea, retractions,
      crackles, and hypoxia. The aim of this study was to report and discuss the
      clinical, imaging, and histopathological findings in a series of NEHI cases at a
      tertiary pediatric hospital, with an emphasis on diagnostic criteria and clinical
      outcomes. METHODS: Between 2003 and 2011, 12 full-term infants were diagnosed
      with NEHI, based on clinical and tomographic findings. Those infants were
      followed for 1-91 months. Four infants were biopsied, and the histopathological
      specimens were stained with bombesin antibody. RESULTS: In this case series,
      symptoms appeared at birth in 6 infants and by 3 months of age in the remaining
      6. In all of the cases, NEHI was associated with acute respiratory infection. The
      most common initial chest HRCT findings were ground-glass opacities that were in
      the middle lobe/lingula in 12 patients and in other medullary areas in 10. Air
      trapping was the second most common finding, being observed in 7 patients. Follow
      up HRCT scans (performed in 10 patients) revealed normal results in 1 patient and
      improvement in 9. The biopsy findings were nonspecific, and the staining was
      positive for bombesin in all samples. Confirmation of NEHI was primarily based on
      clinical and tomographic findings. Symptoms improved during the follow-up period
      (mean, 41 months). A clinical cure was achieved in 4 patients. CONCLUSIONS: In
      this sample of patients, the diagnosis of NEHI was made on the basis of the
      clinical and tomographic findings, independent of the lung biopsy results. Most
      of the patients showed clinical improvement and persistent tomographic changes
      during the follow-up period, regardless of the initial severity of the disease or
      type of treatment.

PMID- 24310631
TI  - Prevalence of and factors influencing smoking among medical and non-medical
      students in Tbilisi, Georgia.
AB  - OBJECTIVE: Smoking is a serious problem that has a devastating impact on health.
      The objective of this study was to describe the prevalence of and factors
      influencing smoking among medical and non-medical students in Tbilisi, Georgia,
      as well as to determine whether medical education has an impact on smoking.
      METHODS: A cross-sectional study was carried out at Tbilisi State Medical
      University and Tbilisi State University, both of which are located in Tbilisi,
      Georgia. A total of 400 4th-year students (200 students at each university) were
      asked to complete standardized questionnaires. RESULTS: Of the sample as a whole,
      48.75% were identified as smokers and 51.25% were identified as nonsmokers. The
      mean age was 20.24 years among smokers and 20.26 years among nonsmokers. Of the
      medical students, 49.5% were smokers, as were 48.0% of the non-medical students.
      The male-to-female ratio in the study population was 0.9:1.1. Smoking was found
      to have a strong relationship with gender, males accounting for 65% of all
      smokers. Of the smokers, 56.9% stated that they would like to quit smoking (for
      health or financial reasons). Of the medical students, 59.5% expressed a
      willingness to quit smoking, as did 54.2% of the non-medical students.
      CONCLUSIONS: There is a need to improve smoking education for undergraduate
      students. Special attention should be given to the inclusion of anti-smoking
      education in undergraduate curricula, as well as to the implementation of smoking
      prevention campaigns at institutions of higher education. However, such measures
      will be effective only if tobacco control policies are strictly enforced on the
      national level as well.

PMID- 24310632
TI  - The outcome of tuberculosis treatment in subjects with chronic kidney disease in
      Brazil: a multinomial analysis.
AB  - OBJECTIVE: To analyze the association between clinical/epidemiological
      characteristics and outcomes of tuberculosis treatment in patients with
      concomitant tuberculosis and chronic kidney disease (CKD) in Brazil. METHODS: We
      used the Brazilian Ministry of Health National Case Registry Database to identify
      patients with tuberculosis and CKD, treated between 2007 and 2011. The
      tuberculosis treatment outcomes were compared with epidemiological and clinical
      characteristics of the subjects using a hierarchical multinomial logistic
      regression model, in which cure was the reference outcome. RESULTS: The
      prevalence of CKD among patients with tuberculosis was 0.4% (95% CI: 0.37-0.42%).
      The sample comprised 1,077 subjects. The outcomes were cure, in 58%; treatment
      abandonment, in 7%; death from tuberculosis, in 13%; and death from other causes,
      in 22%. The characteristics that differentiated the ORs for treatment abandonment
      or death were age; alcoholism; AIDS; previous noncompliance with treatment;
      transfer to another facility; suspected tuberculosis on chest X-ray; positive
      results in the first smear microscopy; and indications for/use of directly
      observed treatment, short-course strategy. CONCLUSIONS: Our data indicate the
      importance of sociodemographic characteristics for the diagnosis of tuberculosis
      in patients with CKD and underscore the need for tuberculosis control strategies
      targeting patients with chronic noncommunicable diseases, such as CKD.

PMID- 24310633
TI  - Evaluation of manual resuscitators used in ICUs in Brazil.
AB  - OBJECTIVE: To evaluate the performance of manual resuscitators (MRs) used in
      Brazil in accordance with international standards. METHODS: Using a respiratory
      system simulator, four volunteer physiotherapists employed eight MRs (five
      produced in Brazil and three produced abroad), which were tested for inspiratory
      and expiratory resistance of the patient valve; functioning of the pressure
      limiting valve; and tidal volume (VT) generated when the one-handed and two
      handed techniques were used. The tests were performed and analyzed in accordance
      with the American Society for Testing and Materials (ASTM) F920-93 criteria.
      RESULTS: Expiratory resistance was greater than 6 cmH2O . L-1 . s-1 in only one
      MR. The pressure-limiting valve, a feature of five of the MRs, opened at low
      pressures (< 17 cmH2O), and the maximal pressure was 32.0-55.9 cmH2O. Mean VT
      varied greatly among the MRs tested. The mean VT values generated with the one
      handed technique were lower than the 600 mL recommended by the ASTM. In the
      situations studied, mean VT was generally lower from the Brazilian-made MRs that
      had a pressure-limiting valve. CONCLUSIONS: The resistances imposed by the
      patient valve met the ASTM criteria in all but one of the MRs tested. The
      pressure-limiting valves of the Brazilian-made MRs usually opened at low
      pressures, providing lower VT values in the situations studied, especially when
      the one-handed technique was used, suggesting that both hands should be used and
      that the pressure-limiting valve should be closed whenever possible.

PMID- 24310635
TI  - Pneumomediastinum, subcutaneous emphysema, and pneumothorax after a pulmonary
      function testing in a patient with bleomycin-induced interstitial pneumonitis.
AB  - Spontaneous pneumomediastinum is an uncommon event, the clinical picture of which
      includes retrosternal chest pain, subcutaneous emphysema, dyspnea, and dysphonia.
      The pathophysiological mechanism involved is the emergence of a pressure gradient
      between the alveoli and surrounding structures, causing alveolar rupture with
      subsequent dissection of the peribronchovascular sheath and infiltration of the
      mediastinum and subcutaneous tissue with air. Known triggers include acute
      exacerbations of asthma and situations that require the Valsalva maneuver. We
      described and documented with HRCT scans the occurrence of pneumomediastinum
      after a patient with bleomycin-induced interstitial lung disease underwent
      pulmonary function testing. Although uncommon, the association between pulmonary
      function testing and air leak syndromes has been increasingly reported in the
      literature, and lung diseases, such as interstitial lung diseases, include
      structural changes that facilitate the occurrence of this complication. 

PMID- 24310634
TI  - Obstructive sleep apnea and asthma.
AB  - Symptoms of sleep-disordered breathing, especially obstructive sleep apnea
      syndrome (OSAS), are common in asthma patients and have been associated with
      asthma severity. It is known that asthma symptoms tend to be more severe at night
      and that asthma-related deaths are most likely to occur during the night or early
      morning. Nocturnal symptoms occur in 60-74% of asthma patients and are markers of
      inadequate control of the disease. Various pathophysiological mechanisms are
      related to the worsening of asthma symptoms, OSAS being one of the most important
      factors. In patients with asthma, OSAS should be investigated whenever there is
      inadequate control of symptoms of nocturnal asthma despite the treatment
      recommended by guidelines having been administered. There is evidence in the
      literature that the use of continuous positive airway pressure contributes to
      asthma control in asthma patients with obstructive sleep apnea and uncontrolled
      asthma. 

PMID- 24310636
TI  - Cryptococcosis, silicosis, and tuberculous pseudotumor in the same pulmonary
      lobe.
AB  - Tuberculosis and cryptococcosis are infectious diseases that can result in the
      formation of single or multiple nodules in immunocompetent patients. Exposure to
      silica is known to raise the risk of infection with Mycobacterium tuberculosis.
      We report the case of an elderly man with no history of opportunistic infections
      and no clinical evidence of immunodeficiency but with a six-month history of dry
      cough and nocturnal wheezing. A chest X-ray revealed a mass measuring 5.0 * 3.5
      cm in the right upper lobe. The diagnostic approach of the mass revealed
      tuberculosis. The histopathological analysis of the surrounding parenchyma
      reveled silicosis and cryptococcosis. Cryptococcosis was also found in masses
      identified in the mediastinal lymph nodes. The surgical approach was indicated
      because of the degree of pleuropulmonary involvement, the inconclusive results
      obtained with the invasive and noninvasive methods applied, and the possibility
      of malignancy. This case illustrates the difficulty inherent to the assessment of
      infectious or inflammatory pulmonary pseudotumors, the differential diagnosis of
      which occasionally requires a radical surgical approach. Despite the presence of
      respiratory symptoms for six months, the first chest X-ray was performed only at
      the end of that period. We discuss the possible pathogenic mechanisms that might
      have led to the combination of three types of granulomatous lesions in the same
      lobe, and we emphasize the need for greater awareness of atypical presentations
      of pulmonary tuberculosis. 

PMID- 24310637
TI  - Epipericardial fat necrosis: an unusual cause of chest pain.

PMID- 24310638
TI  - Thoracic lipomas simulating metastasis.

PMID- 24310639
TI  - Mortality distribution due to tracheal, lung, and bronchial cancer by gender,
      Brazil, 1980-2010.

PMID- 24310640
TI  - Mediastinal cyst as a cause of severe airway compression and dysphonia.

PMID- 24310641
TI  - Selected skin diseases with systemic involvement.
AB  - The skin is often a window to systemic disease that is available to the trained
      eye of the dermatologist. Herein, we focus on four dermatoses with associated
      systemic conditions of interest: scleromyxedema and monoclonal gammopathy,
      nephrogenic systemic fibrosis in the setting of renal insufficiency, dermatitis
      herpetiformis and celiac disease, and psoriasis as a risk factor for
      cardiovascular disease. Dermatologists can play a crucial role in recognizing the
      cutaneous manifestations linked with these conditions. Identifying the related
      underlying disorder will contribute to appropriate diagnosis and improved
      management. 

PMID- 24310642
TI  - Topical agents for hair growth promotion: what is out there?
AB  - Hair loss is a widespread complaint that carries a significant psychosocial
      burden for affected individuals. Androgenetic alopecia (AGA) is the predominant
      cause of hair loss seen in the dermatology clinic. Although a range of therapies
      are available, minoxidil remains the only approved topical treatment for AGA.
      Promising new topical agents are under current investigation. 

PMID- 24310643
TI  - Investigation of biogeochemical functional proxies in headwater streams across a
      range of channel and catchment alterations.
AB  - Historically, headwater streams received limited protection and were subjected to
      extensive alteration from logging, farming, mining, and development activities.
      Despite these alterations, headwater streams provide essential ecological
      functions. This study examines proxy measures of biogeochemical function across a
      range of catchment alterations by tracking nutrient cycling (i.e., inputs,
      processing, and stream loading) with leaf litter fall, leaf litter decomposition,
      and water quality parameters. Nutrient input and processing remained highest in
      second growth forests (the least altered areas within the region), while recently
      altered locations transported higher loads of nutrients, sediments, and
      conductivity. Biogeochemical functional proxies of C and N input and processing
      significantly, positively correlated with rapid assessment results (Pearson
      coefficient = 0.67-0.81; P = 0.002-0.016). Additionally, stream loading equations
      demonstrate that N and P transport, sediment, and specific conductivity
      negatively correlated with rapid assessment scores (Pearson coefficient = 0.56
      0.81; P = 0.002-0.048). The observed increase in stream loading with lower rapid
      assessment scores indicates that catchment alterations impact stream chemistry
      and that rapid assessments provide useful proxy measures of function in headwater
      ecosystems. Significant differences in nutrient processing, stream loading, water
      quality, and rapid assessment results were also observed between recently altered
      (e.g., mined) headwater streams and older forested catchments (Mann-Whitney U =
      24; P = 0.01-0.024). Findings demonstrate that biogeochemical function is reduced
      in altered catchments, and rapid assessment scores respond to a combination of
      alteration type and recovery time. An analysis examining time and economic
      requirements of proxy measurements highlights the benefits of rapid assessment
      methods in evaluating biogeochemical functions. 

PMID- 24310644
TI  - Restoring forest landscapes: important lessons learnt.
AB  - Forest restoration at large scales, or landscapes, is an approach that is
      increasingly relevant to the practice of environmental conservation. However,
      implementation remains a challenge; poor monitoring and lesson learning lead to
      similar mistakes being repeated. The World Wildlife Fund (WWF), the global
      conservation organization, recently took stock of its 10 years of implementation
      of forest landscape restoration. A significant body of knowledge has emerged from
      the work of the WWF and its partners in the different countries, which can be of
      use to the wider conservation community, but for this to happen, lessons need to
      be systematically collected and disseminated in a coherent manner to the broader
      conservation and development communities and, importantly, to policy makers. We
      use this review of the WWF's experiences and compare and contrast it with other
      relevant and recent literature to highlight 11 important lessons for future large
      scale forest restoration interventions. These lessons are presented using a
      stepwise approach to the restoration of forested landscapes. We identify the need
      for long-term commitment and funding, and a concerted and collaborative effort
      for successful forest landscape restoration. Our review highlights that
      monitoring impact within landscape-scale forest restoration remains inadequate.
      We conclude that forest restoration within landscapes is a challenging yet
      important proposition that has a real but undervalued place in environmental
      conservation in the twenty-first century.

PMID- 24310645
TI  - Adolescent egocentrism: Exploration into possible contributions of parent-child
      relations.
AB  - A family relations model for the study of adolescent egocentrism was tested in an
      exploratory study of the relationship between parental socialization styles and
      adolescents' imaginary audience behavior. A sample of adolescent boys (n=58) and
      girls (n=57) responded to Heilbrun's Parent-Child Interaction Rating Scale and
      Schaefer's Parent-Behavior Inventory and completed Elkind and Bowen's Imaginary
      Audience Scale. As hypothesized, rejection-control was associated with increased
      imaginary audience behavior, while physical affect was negatively related to self
      consciousness. Sex differences were noted, with rejection-control being most
      important in predicting self-consciousness for boys and physical affect being the
      best predictor of girls' egocentrism behavior. The data provide an alternative
      model to a cognitive developmental perspective of adolescent egocentrism
      development. 

PMID- 24310646
TI  - An extension of Marcia's Identity Status Interview into the interpersonal domain.
AB  - This article describes an extension of Marcia's (1966) Identity Status Interview
      into three interpersonal domains: friendships, dating, and sex roles. The
      Identity Status Interview method is assessed favorably in terms of identity
      theory, justification for the three new sections is provided on the basis of
      theory and research on sex differences in adolescent identity, and methodological
      refinements in the interview are described. A study is reported in which the
      extended interview was administered to 41 male and 40 female high school juniors
      and seniors. Average percentage of exact agreement for ratings of exploration,
      commitment, and identity status was over 70% when two coders were used and over
      94% when the ratings of two out of three coders were used. It is concluded that
      this extended interview is psychometrically sound and provides a method for
      assessing interpersonal issues salient to contemporary adolescents. 

PMID- 24310647
TI  - Who stays? who leaves? an examination of sex differences in staying and leaving.
AB  - This article examines some of the major variables associated with the "staying"
      and "leaving" process, particularly as it operates similarly or differentially
      for male and female adolescents. Sixty attitude statements about aspects of
      school, parents, peers, teachers, and value orientations were obtained from 796
      adolescents and factor analyzed. This subset of independent variables, together
      with a set of personality and ability measures, was then used to predict
      "staying" or "leaving" status. The discriminant analysis was undertaken using
      "leaving" status and sex (LVSEX) as the dependent variable. Using a stepwise
      solution method of discriminant analysis, two significant functions were
      identified-the first suggesting a sex dimension, the second a stayer-leaver
      dimension. 

PMID- 24310648
TI  - Evaluation of methods for analysis of lead in air particulates: an intra
      laboratory and inter-laboratory comparison.
AB  - In 2008, the United States Environmental Protection Agency (USEPA) set a new
      National Ambient Air Quality Standard (NAAQS) for lead in total suspended
      particulate matter (Pb-TSP) which called for significant decreases in the
      allowable limits. The Federal Reference Method (FRM) for Pb-TSP promulgated in
      1978 prescribes analysis of Pb by flame atomic absorption spectroscopy (FAAS),
      but the new limits approach the limits of quantitation of FAAS. On August 2,
      2013, the USEPA finalized a new FRM for Pb-TSP. This new FRM describes two
      extraction methods and analysis by inductively coupled plasma-mass spectrometry
      (ICP-MS). The study described here was performed to evaluate the use of ICP-MS in
      the analysis of Pb-TSP for implementation of this new FRM. A multi-laboratory
      study of the new FRM demonstrated acceptable intra- and inter-laboratory
      precision and comparability for glass fiber, quartz, and PTFE filters, and
      acceptable accuracy for the analysis of three National Institute of Standards and
      Technology (NIST) Standard Reference Materials (SRMs). A comparison was made
      between analytical results obtained using the 1978 FRM and those obtained using
      the new FRM. The results demonstrate that the ICP-MS method performs acceptably
      for the determination of Pb-TSP with lower limits of quantitation and strong
      inter- and intra-laboratory precision. 

PMID- 24310649
TI  - Decisive evidence on a smaller-than-you-think phenomenon: revisiting the "1-in-X"
      effect on subjective medical probabilities.
AB  - Accurate perception of medical probabilities communicated to patients is a
      cornerstone of informed decision making. People, however, are prone to biases in
      probability perception. Recently, Pighin and others extended the list of such
      biases with evidence that "1-in-X" ratios (e.g., "1 in 12") led to greater
      perceived probability and worry about health outcomes than "N-in-X*N" ratios
      (e.g., "10 in 120"). Subsequently, the recommendation was to avoid using "1-in-X"
      ratios when communicating probabilistic information to patients. To warrant such
      a recommendation, we conducted 5 well-powered replications and synthesized the
      available data. We found that 3 out of the 5 replications yielded statistically
      nonsignificant findings. In addition, our results showed that the "1-in-X" effect
      was not moderated by numeracy, cognitive reflection, age, or gender. To quantify
      the evidence for the effect, we conducted a Bayes factor meta-analysis and a
      traditional meta-analysis of our 5 studies and those of Pighin and others (11
      comparisons, N = 1131). The meta-analytical Bayes factor, which allowed
      assessment of the evidence for the null hypothesis, was very low, providing
      decisive evidence to support the existence of the "1-in-X" effect. The
      traditional meta-analysis showed that the overall effect was significant (Hedges'
      g = 0.42, 95% CI 0.29-0.54). Overall, we provide decisive evidence for the
      existence of the "1-in-X" effect but suggest that it is smaller than previously
      estimated. Theoretical and practical implications are discussed.

PMID- 24310650
TI  - Sulfuric acid intercalated graphite oxide for graphene preparation.
AB  - Graphene has shown enormous potential for innovation in various research fields.
      The current chemical approaches based on exfoliation of graphite via graphite
      oxide (GO) are potential for large-scale synthesis of graphene but suffer from
      high cost, great operation difficulties, and serious waste discharge. We report a
      facile preparation of graphene by rapid reduction and expansion exfoliation of
      sulfuric acid intercalated graphite oxide (SIGO) at temperature just above 100
      degrees C in ambient atmosphere, noting that SIGO is easily available as the
      immediate oxidation descendent of graphite in sulfuric acid. The oxygenic and
      hydric groups in SIGO are mainly removed through dehydration as catalyzed by the
      intercalated sulfuric acid (ISA). The resultant consists of mostly single layer
      graphene sheets with a mean diameter of 1.07 MUm after dispersion in DMF. This
      SIGO process is reductant free, easy operation, low-energy, environmental
      friendly and generates graphene with low oxygen content, less defect and high
      conductivity. The provided synthesis route from graphite to graphene via SIGO is
      compact and readily scalable. 

PMID- 24310651
TI  - Plastid and nuclear DNA synthesis are not coupled in suspension cells ofNicotiana
      tabacum.
AB  - The relationship between nuclear and plastid DNA synthesis in cultured tobacco
      cells was measured by following(3)H-thymidine incorporation into total cellular
      DNA in the absence or presence of specific inhibitors. Plastid DNA synthesis was
      determined by hybridization of total radiolabeled cellular DNA to cloned
      chloroplast DNA.Cycloheximide, an inhibitor of nuclear encoded cytoplasmic
      protein synthesis, caused a rapid and severe inhibition of nuclear DNA synthesis
      and a delayed inhibition of plastid DNA synthesis. By contrast, chloramphenicol
      which only inhibits plastid and mitochondrial protein production, shows little
      inhibition of either nuclear or plastid DNA synthesis even after 24 h of exposure
      to the cells.The inhibition of nuclear DNA synthesis by aphidicolin, which
      specifically blocks the nuclear DNA polymerasealpha, has no significant effect on
      plastid DNA formation. Conversely, the restraint of plastid DNA synthesis exerted
      by low levels of ethidium bromide has no effect on nuclear DNA synthesis.These
      results show that the synthesis of plastid and nuclear DNA are not coupled to one
      another. However, both genomes require the formation of cytoplasmic proteins for
      their replication, though our data suggest that different proteins regulate the
      biosynthesis of nuclear and plastid DNA. 

PMID- 24310652
TI  - The presence and photoregulation of protochlorophyllide reductase in green
      tissues.
AB  - The enzyme protochlorophyllide (pchlide) reductase has been identified amongst
      the peptides, resolved by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE), of chloroplast membranes from oat and barley plants.
      In support of this identification the enzymic activity associated with the enzyme
      has also been measured in the same preparations. A higher level of enzyme was
      found in plants which had been darkened prior to extraction. Based on this data,
      mechanisms for the light regulated diurnal variation of the reductase are
      discussed. 

PMID- 24310653
TI  - Interaction of spermidine with viral RNA and its influence on protein synthesis.
AB  - Addition of spermidine to a cell-free protein synthesizing system from wheat germ
      programmed with total brome mosaic virus (BMV) RNA resulted in a several-fold
      stimulation of amino acid incorporation. Increasing the spermidine concentration
      in the system led to inhibition of the overall protein synthesis, but the
      production of longer polypeptides was inhibited much more than that of the coat
      protein (shorter product). Analysis of the products synthesized under direction
      of BMV RNA 3 (longer product) and RNA 4 (coat protein) revealed that optimal
      translation of RNA 3 occurred at a much lower concentration of spermidine than
      that of RNA 4. Binding experiments with radioactive spermidine and BMV RNAs
      showed that the saturation of spermidine binding is achieved at a lower
      concentration of spermidine for RNA 3 than for RNA 4, which may suggest that the
      structure of RNA 4 is more compact than that of RNA 3. Taking into account the
      binding obtained at a spermidine concentration corresponding to optimal
      conditions of protein synthesis, it may be concluded that the optimum translation
      of these two mRNAs occurs when there is a similar level of RNA charge
      neutralisation, which implies a similar level of RNA structure stabilisation. 

PMID- 24310654
TI  - Biochemical and serological characterization of b-proteins fromNicotiana species.
AB  - Proteins associated with the hypersensitive response (b-proteins) were purified
      from variousNicotiana species and compared biochemically and serologically. The
      method developed to purify proteins b1, b2 and b3 ofN. tabacum cv. Xanthi-nc was
      used to purify b-proteins present inN. sylvestris (b0, b1 and b3) andN.
      tomentosiformis (b2), the parental species ofN. tabacum, and b1" from bothN.
      glutinosa andN. debneyi. Ultracentrifugation and amino acid analysis of some of
      these proteins has shown that they are very similar and that they are all
      monomers in their native form (mol wt = 15 700 for b0, b1, b2 and b3; mol wt = 13
      800 for b1").Based on their reactions to an antiserum produced against protein b1
      ofN. tabacum cv. Xanthi-nc, 3 serological groups can be recognized which are
      independent of the source species (I) b0 and b1, (II) b1" and b2, (III) b3. Thus,
      proteins in the same serological group but from different species are more
      closely related than the b-proteins in different serological groups but present
      in the same species. The implication of this site on the possible phylogeny of b
      proteins is discussed.Serological tests confirmed the b-protein present as a
      constitutive component in the virus resistant interspecific hybrids ofN.
      glutinosa *N. debneyi as protein b1". 

PMID- 24310655
TI  - Multiple transcripts for higher plantrbcL andatpB genes and localization of the
      transcription initiation site of therbcL gene.
AB  - We have compared therbcL andatpB transcription units from spinach, maize, and
      pea. In most cases multiple transcripts were found for a given chloroplast gene.
      The 5' termini of these transcripts were determined by S1 nuclease protection and
      primer extension analyses. TherbcL transcripts have 5' termini 178-179 and 64
      nucleotides (spinach), 300 and 59-63 nucleotides (maize), and 178 and 65
      nucleotides (pea) upstream from their respective protein coding regions. TheatpB
      transcripts have 5' termini (453-454, 272-273, 179, and 99 nucleotides (spinach),
      298-302 nucleotides (maize), and 351-355 nucleotides (pea) upstream from their
      respective protein coding regions. The intergenic distance between therbcL
      andatpB genes is relatively constant (152 to 157 base pairs) among the three
      chloroplast genomes. In spinach, maize, and pea, the 80 base pairs surrounding
      the 5' end of therbcL gene (+/-40 base pairs) have 85% sequence homology.
      Similarly, the 60 base pairs preceding theatpB gene have 48% sequence homology.
      Both genes have '-10' and '-35' regions that resemble the prokaryotic consensus
      promoter sequence. The larger, but not smaller,rbcL transcripts from spinach and
      pea can be labeled with alpha-(32)P-GTP by guanylyltransferase. These data
      suggest that DNA sequences 178-179 (spinach), 300 (maize), and 178 (pea) base
      pairs before therbcL protein coding regions represent sites of transcription
      initiation. The sequences 59-65 base pairs before therbcL protein coding regions
      may correspond to sites of RNA cleavage. 

PMID- 24310656
TI  - The detection of PR (b) protein and TMV by ELISA in systemic and localised virus
      infections of tobacco.
AB  - An antiserum was prepared to the b1 protein purified from TMV infectedN. tabacum
      cv. Xanthi-nc leaves and used to study PR proteins. The Xanthi-nc proteins b2 and
      b3 were shown to be serologically closely related to b1. Antisera to b1 protein
      and TMV were used in a F(ab')2 enzyme linked immunosorbent assay to monitor PR
      protein and TMV concentrations, respectively, during the first 6 days of a
      systemic TMV infection (cv. Xanthi) and a localised TMV infection (cv. Xanthi
      nc). 

PMID- 24310657
TI  - Molecular and genetic analysis of the chloroplast ATPase ofChlamydomonas.

PMID- 24310658
TI  - IGF1(CA)19 and IGFBP-3-202A/C gene polymorphism and cancer risk: a meta-analysis.
AB  - Insulin-like growth factor 1 (IGF1)(CA)19 and insulin-like growth factor-binding
      protein-3 (IGFBP-3)-202A/C gene polymorphisms had been focused by many
      epidemiological studies recently, which were associated with common cancer risk
      including colorectal, breast, prostate, and lung cancer. However, the findings of
      epidemiological investigations are not coincident. We did a systematic review and
      meta-analysis of case-control studies, including studies nested in cohorts, of
      the association between IGF1(CA)19 and IGFBP-3-202A/C gene polymorphism and
      prostate, colorectal, premenopausal and postmenopausal breast cancer. We
      identified 17 eligible studies (24 datasets), which included 9,744 cases and
      11,332 controls. The result displays that individuals carrying (CA)19 allele had
      a subtly decreased risk of all cancer sites [OR(95% CI) 0.92(0.87,0.97);
      0.882(0.809,0.962); 0.902(0.849,0.958)] and postmenopausal breast cancer [OR(95%
      CI) 0.893(0.832,0.959); 0.834(0.719,0.968); 0.862(0.776,0.958)] in allele
      contrast model, CA19/CA19 vs. non-CA19/non-CA19 model, and recessive genetic
      model. In subgroup analysis according to ethnicities, (CA)19 repeat polymorphism
      had an increased risk of common cancers in Asian [OR (95% CI) of allele contrast
      model: 1.105(1.000,1.224); additive model: 1.103(0.844,1.441),
      1.197(1.013,1.413); recessive model: 1.039(0.831,1.300); and dominant model:
      1.191(1.030,1.376)]. On the other hand, IGFBP-3-202A/C gene polymorphism did not
      seem to be associated with all the cancer sites in any genetic model and
      ethnicity. In conclusion, the result of this meta-analysis indicates that the
      IGF1(CA)19 polymorphism is a candidate gene polymorphism for cancer
      susceptibility regardless of environmental factors, especially in Asian.

PMID- 24310659
TI  - Autophagic and proteolytic processes in the Harderian gland are modulated during
      the estrous cycle.
AB  - The Syrian hamster Harderian gland (HG) is an organ that undergoes physiological
      autophagy in response to oxidative stress induced by porphyrin production.
      Porphyrin production in the HG has marked sex differences and is closely linked
      to reproductive function. In the present study, we observed that the estrous
      cycle and associated estrogen variations may affect oxidative-stress-induced
      proteolytic processes. In particular, significant changes in autophagic activity
      were detected during the estrous cycle. Notably, increased activation of
      macroautophagy as well as chaperone-mediated autophagy in the estrus phase
      coincided with a minimal antioxidant capability and the highest protein damage
      levels. By contrast, autophagic machinery was found to be blocked in the diestrus
      phase, likely due to mammalian target of rapamycin activation, which could be
      corroborated by the subsequent pS6K activation. Analogous results were observed
      regarding proteasome activity, which also showed maximal activity in the estrus
      phase. Interestingly, all these mechanisms were associated with important
      morphological changes in the HG during the estrous cycle. We observed
      statistically significant increases in Type II cells, which may be related to
      extensive autophagy in the estrus phase. Physiologically, this would result in a
      significant release of porphyrins specifically when females are more receptive.
      These data support the role of porphyrins as pheromones, as other authors have
      previously suggested, thus making the HG a scent organ. In addition, these
      results suggest a porphyrin-based approach to the treatment of porphyria during
      pregnancy, a condition for which no treatment is currently known. 

PMID- 24310660
TI  - Benefits of early detection and treatment of human immunodeficiency virus
      infections.

PMID- 24310661
TI  - Intraductal radiofrequency ablation of tumour ingrowth into an uncovered metal
      stent used for inoperable cholangiocarcinoma.
AB  - A 91-year-old woman diagnosed to have an inoperable cholangiocarcinoma had an
      uncovered metal stent inserted for palliative drainage. About 1.5 years later,
      tumour ingrowth into the metal stent caused cholangitis. Intraductal
      radiofrequency ablation was applied to create local coagulative tumour necrosis
      and the necrotic tissue was removed via a balloon catheter. A plastic stent was
      inserted to empirically treat any ensuing potential bile duct injury. The patient
      was discharged without complication with good palliative drainage. Intraductal
      radiofrequency ablation is a new technique for the treatment of metal stent
      occlusion due to tumour ingrowths. This is the first case report of this
      relatively safe and feasible new technique for the treatment of tumour ingrowth
      into a metal stent used as palliation for malignant biliary obstruction. 

PMID- 24310662
TI  - Aorto-oesophageal fistula and aortic pseudoaneurysm caused by a swallowed fish
      bone.
AB  - We describe a rare case of aorto-oesophageal fistula and aortic pseudoaneurysm in
      a middle-aged man, who presented with chest pain and haematemesis 1 week after
      swallowing a fish bone. Oesophagogastroduodenoscopy and computed tomographic
      angiography findings were consistent with oesophageal perforation, proximal
      descending aortic pseudoaneurysm, and aorto-oesophageal fistula. Thoracic
      endovascular aortic repair was performed. The patient died from severe
      mediastinal sepsis. Early surgical intervention and broad-spectrum antibiotic
      therapy are crucial in preventing life-threatening mediastinal infection. 

PMID- 24310663
TI  - Uncommon cause of severe pneumonia: co-infection of influenza B and
      Streptococcus.
AB  - Influenza and pneumococcus co-infection can cause severe morbidity and mortality.
      Usually, this entails influenza A, while infection by influenza B is rarely
      serious. The literature describes influenza A epidemics leading to prolific loss
      of lives, notably the 1918 epidemic was blamed for the deaths of 40 to 50 million
      people. In this report, four patients were infected by influenza B during the
      influenza epidemic of 2011/12 in Hong Kong. All of them were previously healthy
      and had no chronic diseases; they were admitted to the hospital due to influenza
      like symptoms. They rapidly deteriorated with multi-organ failure, and were
      subsequently diagnosed to be infected with influenza B and streptococci that gave
      rise to severe pneumonia. Three of them were infected with Streptococcus
      pneumoniae and one with Streptococcus pyogenes. All of them had leukopenia,
      septic shock, and acute kidney injury; two of whom died despite aggressive
      antibiotic treatment and organ support in the intensive care unit. According to
      the literature, this is the second case report of severe invasive pneumococcal
      pneumonia secondary to influenza B infection. 

PMID- 24310664
TI  - Low-dose subcutaneous alemtuzumab is a safe and effective treatment for chronic
      acquired pure red cell aplasia.
AB  - Three patients with pure red cell aplasia, with or without co-existing large
      granular lymphocytic leukaemia, who remained transfusion-dependent despite
      treatment with established first-line therapy, were treated with low-dose
      subcutaneous alemtuzumab 15 mg twice to thrice per week, for 3 to 4 weeks. The
      mean response time was 17 days compared with a response time of at least 61 days
      on standard first-line therapy. There were no serious side-effects and the mean
      duration of remission was 13 months. Low-dose subcutaneous alemtuzumab is a safe
      and effective treatment for pure red cell aplasia and further trials should be
      conducted to compare the long-term effectiveness of this treatment with
      conventional therapy. 

PMID- 24310665
TI  - Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.
AB  - In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari
      syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural
      effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His
      clinical (including imaging) features were compatible with Budd-Chiari syndrome.
      Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our
      case, extensive workup performed to look for the underlying cause of Budd-Chiari
      syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his
      herbal drinks. 

PMID- 24310666
TI  - Oculopharyngeal muscular dystrophy: underdiagnosed disease in Hong Kong.
AB  - Despite the advances in the understanding of the molecular basis for
      oculopharyngeal muscular dystrophy in the last decade, it remains an
      underdiagnosed disease, especially among the Chinese. In the presence of a
      positive family history and late-onset ptosis, dysphagia, and proximal muscle
      weakness (its cardinal features), we suggest that PABPN1 gene analysis should be
      the first-line investigation to rule out this condition. Muscle biopsy can be
      reserved for atypical cases. Non-specific mitochondrial changes in the muscle
      specimens of these patients should be appreciated, so as to avoid diagnostic
      confusion. It is hoped that greater awareness among medical professionals and
      judicious use of PABPN1 gene analysis will lead to earlier diagnosis, better
      management, and avoidance of unnecessary invasive investigations of affected
      patients. 

PMID- 24310667
TI  - Tuberculin sensitivity testing in human immunodeficiency virus-infected patients.

PMID- 24310668
TI  - Authors' reply.

PMID- 24310669
TI  - Bochdalek hernia in an octogenarian.

PMID- 24310670
TI  - Laparoscopic removal of an eroding Mirena coil through the sigmoid colon.

PMID- 24310671
TI  - Women, science and research.

PMID- 24310672
TI  - [Effective coverage to manage domestic violence against women in Mexican
      municipalities: limits of metrics].
AB  - The study estimated the effective coverage of health services in primary care for
      the management of domestic violence against women in three municipalities in
      Mexico. We estimated the prevalence and severity of violence using a validated
      scale, and the effective coverage proposed by Shengelia and partners with any
      modifications. Quality care was considered when there was a suggestion to report
      it to authorities. The use and quality of care was low in the three
      municipalities analyzed, used most frequently when there was sexual or physical
      violence. Effective coverage was 29.41%, 16.67% and zero in Guachochi, Jojutla
      and Tizimin, respectively. The effective coverage indicator had difficulties in
      measuring events and responses that were not based on biomedical models. Findings
      suggest that the indicator can be improved by incorporating other dimensions of
      quality. 

PMID- 24310673
TI  - [Reliability of an instrument to classify newborns according to care complexity].
AB  - In most maternity units, the physician classifies, evaluates, and determines
      which unit will receive the newborn (NB) after birth. Evaluation occurs in the
      delivery room, taking into consideration the following factors: birth weight,
      gestational age, and behaviors that define the clinical picture and disease. This
      observational study evaluates the reliability of an NB classification instrument.
      The study was conducted at the nursery of a public hospital in Sao Paulo. Nine
      nurses applied the instrument to 63 NB, with two of the nurses working
      simultaneously in each of the nursery's five sectors. The Kappa level of
      agreement among the nurses was found to be excellent for most care areas (69.0%).
      It was concluded that there was a consensus and agreement among the nurses that
      the instrument was complete, easy to understand and applicable, but was very time
      consuming. The nurses recognize the instrument's importance for the allocation of
      professionals, organization, and care planning. 

PMID- 24310674
TI  - [Central venous catheterization in pediatric and neonatal intensive care units].
AB  - This descriptive, prospective cohort study aimed to analyze the process of
      central venous catheterization in neonatal intensive care and pediatric units;
      describe the variables related to study characterization, including admission
      unit, age, and sex; and to investigate related variables, such as catheter type,
      reason for insertion, number of lumens, insertion site, type of professional who
      performed the procedure, medication therapy infused, reason for withdrawal,
      length of time catheter was in situ, and mechanical and infectious complications.
      Data collection was performed with 82 charts in the intensive care units (ICUs)
      of the Instituto Fernandes Figueira. In the majority of cases, the indications
      for catheter insertion were prolonged drug infusion and total parenteral
      nutrition. Removal was predominantly required due to mechanical and infectious
      complications. This study assessed the process of central venous catheterization
      with the aim of improving care provided to the neonatal and pediatric patients. 

PMID- 24310675
TI  - [Analgesia and sedation during placement of peripherally inserted central
      catheters in neonates].
AB  - This study aimed to characterize the analgesia and sedation strategies in
      neonates having a peripherally inserted central catheter (PICC) placed, and to
      relate it to the number of venipunctures, duration of procedure and catheter tip
      position. This was a cross-sectional study with prospective data collection,
      conducted in a neonatal intensive care unit of a private hospital in the city of
      Sao Paulo, during the period from August 31, 2010 to July 1, 2011, which
      evaluated 254 PICC insertions. The adoption of analgesic or sedative strategies
      occurred in 88 (34.6%) catheter placements and was not related to the number of
      venipunctures, duration of procedure or catheter tip position. Intravenous
      administration of midazolam, in 47 (18.5%), and fentanyl, in 19 (7.3%), catheter
      insertions were the most frequent strategies. Wider adoption of analgesic
      strategies is recommended before, during and after the procedure. 

PMID- 24310676
TI  - [The perceptions of families with children having chronic diseases and their
      relationships with healthcare professionals].
AB  - The prevalence of chronic disease in childhood has increased, placing families in
      constant contact with health professionals. In such situations the relationship
      with health professionals has an important role. Few scientific studies address
      this theme, in spite of its being highlighted as fundamental for effective
      interaction. The aim of this study was to characterize how the family of a child
      with a chronic disease perceives its relationship with health professionals.
      Twenty caregivers for children with chronic diseases were interviewed. The
      theoretical and methodological frameworks were, respectively, symbolic
      interactionism and thematic content analysis. The analytical process revealed
      four themes: role of the caregiver, stressful relationships, services and
      professionals, and seeking welcoming relationships. The outcomes of this
      interactional process, which show an incongruity of expectations and behaviors
      between professionals and families, are poor and generate feelings of
      abandonment. These can be eased through listening and understanding by other
      families in similar situations. 

PMID- 24310677
TI  - [Attitudes towards consumption and non-consumption of alcohol among high school
      students in Mexico].
AB  - The objective of this study was to identify differences in high school students'
      attitudes towards the consumption or non-consumption of alcohol using the theory
      of planned behavior. This was a qualitative, descriptive, cross-sectional study
      that included a sample of 131 students. We found that 74% of students had
      consumed alcohol, and 18.3% exhibited a harmful level of consumption. We also
      found that behavioral beliefs towards consumption were higher among alcohol
      consumers (mean=29.32, median=27.50) than those who did not consume alcohol.
      Moreover, positive beliefs towards consumption were higher among alcohol
      consumers (mean=17.72, median=9.52) than non-consumers, which demonstrates a need
      for preventative programs to strengthen adolescents' beliefs concerning alcohol
      as well as protective factors and healthy lifestyles. 

PMID- 24310678
TI  - [Translation and validation of the Partner Communication Scale - Brazilian
      version with female teenagers].
AB  - This study aimed to describe the process of adaptation and validation of the
      Partner Communication Scale with female adolescents in Fortaleza, CE, Brazil.
      This methodological research, with a quantitative approach, was conducted with
      313 adolescent, aged 14-18 years who had already lost their virginity. The
      transcultural adaptation process was performed by using translation, back
      translation, evaluation of the translations by a committee of judges, and testing
      of the final-draft version. The scale was administered with a sociodemographic
      questionnaire including sexual and reproductive variables, from November 2010 to
      January 2011. The reliability was assessed by the Cronbach's alpha (0.86), which
      demonstrated that it can be successfully applied in the setting of primary health
      care, during nurse consultations. Moreover, the scale allows for the
      identification of factors that hinder or facilitate communication, especially
      concerning sexually transmitted diseases. The scale is an adequate way to verify
      communication between sexual partners in adolescence. 

PMID- 24310679
TI  - Health risk behavior pattern among students from Cartagena, Colombia: prevalence
      and associated variables.
AB  - The aim of the study was to determine the prevalence and variables associated
      with the pattern of risky health behavior (PRHB) among adolescent students in
      Cartagena, Colombia. A cross-sectional study was designed to investigate PRHB in
      a random cluster sample of students from middle and high schools. The
      associations were adjusted by logistic regression. A total of 2,625 students
      participated in this research, with ages from 10 to 20 years, mean=13.8 years
      (SD=2.0), and 54.3% were women. A total of 332 students reported PRHB (12.7%,
      95%CI 11.4-14.0). Age over 15 years (OR=2.19, 95%CI 1.72-2.79), not being
      heterosexual (OR=1.98, 95%CI 1.36-2.87), poor/mediocre academic performance
      (OR=1.87, 95%CI 1.47-2.38), family dysfunction (OR=1.78, 95%CI 1.40-2.28) and
      male gender (OR=1.58, 95%CI 1.24-2.01) were associated with PRHB. One in every
      eight students presented a PRHB. It is important to pay greater attention to
      students who are over 15 years of age, male, not heterosexual, with a
      poor/mediocre academic performance and a dysfunctional family. 

PMID- 24310680
TI  - [Constipation in patients with quadriplegic cerebral palsy: intestinal
      reeducation using massage and a laxative diet].
AB  - Constipation affects 74% of individuals with cerebral palsy. This study aimed to
      evaluate the results of nursing interventions for treating intestinal
      constipation associated with cerebral palsy. This quantitative, prospective,
      comparative study included 50 patients with quadriplegic cerebral palsy and
      constipation. The main conservative measures included daily consumption of
      laxative foods and vegetable oils, increase in fluid intake, and daily intestinal
      massage. Total or partial constipation relief was observed in 90% of the
      patients, with improvement in quality-of-life aspects such as sleep, appetite,
      and irritability, and a significant decrease in rectal bleeding, anal fissure,
      voluntary retention of stools, crying, and pain on defecation. Only 10% of the
      patients required laxative medications. It is recommended that conservative
      measures be used for treating cerebral palsy-related constipation and medications
      be used solely as adjuvants, if needed. 

PMID- 24310681
TI  - [Measure of disease impact: instrument construct validity in patients with
      coronary artery disease].
AB  - This study estimated the known groups construct validity for the Instrument to
      Measure the Impact of Coronary Disease on Patient's Everyday Life (IDCV) related
      to signs and symptoms, ventricular systolic function, left ventricular ejection
      fraction (LVEF) and health-related quality of life (HRQoL) in 153 outpatients
      with coronary artery disease. Data was obtained through application of IDCV and
      Brazilian versions of the instruments The Medical Study 36-item Short Form Health
      Survey - SF-36 and the MacNew Heart Disease Health-related Quality of Life
      Questionnaire . Mann-Whitney test was used to verify the ability of IDCV in
      discriminating impact of signs and symptoms, LVEF and ventricular systolic
      dysfunction. Also, the Kruskal-Wallis test was used to verify the discrimination
      power of the IDCV in relation to HRQoL. It was observed that the IDCV
      discriminated the impact between variables scored in HRQOL quartiles (<=Q1, Q1
      Q3, >=Q3). The study findings contribute for improvement of IDCV in measurement
      of disease impact in coronary artery disease patients. 

PMID- 24310682
TI  - [Correlation between anthropometric indicators and sleep quality among Brazilian
      university students].
AB  - The current study investigated the correlation between anthropometric indicators
      and sleep quality among Brazilian university students using the Pittsburgh Sleep
      Quality Index. A cross-sectional assessment with 702 university students was
      conducted between March 2010 and June 2011. Results showed that cases of obesity
      were more frequent among students who were good sleepers. On the other hand,
      overweight and high cervical and abdominal circumference was most prominent among
      poor sleepers. Thus, apart from the damage caused by sleep disorders alone,
      additional risks due to the association between poor sleep quality and being
      overweight, central obesity, and increased cervical perimeter are highlighted. 

PMID- 24310683
TI  - [Living with hepatitis: impact on the daily life of infected subjects].
AB  - We performed a descriptive, exploratory, and qualitative study, to identify
      changes in the daily life of subjects with hepatitis. The data were collected in
      October 2011 from 12 patients with hepatitis B and/or C, through semi-structured
      interview, and subjected to thematic content analysis. The majority of the
      subjects were diagnosed with hepatitis B. The time of diagnosis ranged from less
      than 6 months to 12 years, and the diagnosis was made mainly through blood
      donation. Only two patients were taking interferon. The results were divided into
      two categories that describe feelings and reactions experienced by the
      interviewees, as well as some lifestyle changes. It was concluded that health
      professionals need to be aware of the complexity of phenomena concerning the
      illness process and life with hepatitis. 

PMID- 24310684
TI  - [Association between insomnia and rheumatoid arthritis in elderly].
AB  - This study aimed to assess symptoms of insomnia in elderly residents in the
      community and its association with rheumatoid arthritis. Descriptive and cross
      sectional study, part of a multicentre research project entitled Fragility in
      Brazilian elderly . A total number of 689 elderly (68.9% female, average age of
      72.2 years) were interviewed using a questionnaire on sociodemographic data and
      clinical conditions. Two tools to identify symptoms of insomnia (the Nottingham
      Health profile) and to screen cognitive impairment (Mini Mental State
      Examination) were also applied. For data analysis, we used descriptive
      statistical techniques and multiple logistic regression, considering a 5%
      significance level. The association between insomnia symptoms and rheumatoid
      arthritis was found to be significant in the multivariate analysis; other
      associated factors were a very poor subjective evaluation of health, being
      retired, and the presence of depression. Health professionals should investigate
      carefully the sleep quality in elderly with rheumatoid arthritis, considering its
      high prevalence in this population. 

PMID- 24310685
TI  - [Production of data for the pre-natal information system in basic health units].
AB  - The objective of this study was to analyze the process of data production for
      Information System Prenatal and Birth (SISPRENATAL) in Basic Health Units of
      Cuiaba, MT, Brazil. This qualitative, exploratory and descriptive study was
      developed in eight units of Basic Health Coordination, through semi-structured
      interviews with professionals who worked with SISPRENATAL (nurses, physicians,
      managers and data entry) and comparative document analysis between system data
      and the written patient records. Data analysis revealed a lack of definition of
      the team's participation in the production of data and different modes of
      completing forms within the system. Professionals' knowledge about many aspects
      of the formswas divergent, completion of the forms was inadequate, and flaws in
      the computerized system were identified. Measures such as professional training,
      the review of the system and its forms are indispensible for the production of
      reliable information about prenatal care in the municipality. 

PMID- 24310686
TI  - [Hospitalisations for ambulatory care sensitive conditions in a Brazilian
      metropolis].
AB  - This study describes the profile of Hospitalisations for Ambulatory Care
      Sensitive Conditions (ACSCs) in Curitiba from 2005 to 2007. An ecological study
      was conducted using the data obtained from the Brazilian Hospital Information
      System (Sistema de Informacoes Hospitalares). Descriptive statistics was used for
      analysis. It was observed that there was a trend toward stabilisation in ACSCs in
      Curitiba, the most frequent causes being angina and heart failure, with an
      increased frequency in females and individuals aged >=65 years. The results were
      similar to those observed in other studies, and almost in their entirety, were
      highly significant from a statistical point of view. However, the studies should
      be viewed with caution because it is an indicator presenting some limitations,
      including the reliability of diagnosis and the use of secondary data. 

PMID- 24310687
TI  - [The structure and flow of the health care network as an instrument of change in
      psychosocial assistance services].
AB  - Changes in mental health care demand changes in the structure and function of
      health care networks. The aim of the present study was to understand how workers
      assess the structure of their network and how they use it as a tool for
      psychosocial rehabilitation. The present qualitative study is part of a larger
      research project, Rehabilitating networks - assessing experiences of innovation
      in network development for psychosocial care . Interviews were conducted with six
      workers at the Therapeutic Home Service (THS) of Alegrete, and four field
      observation notebooks were analyzed. The results revealed the transversal nature
      of the investigated network, the relationships between its various components,
      the strategies used to make non-institutionalized care effective, the
      responsibilities of the network users, and the relationships between the
      residents and the workers in the service and at home. In conclusion, the Alegrete
      network facilitates exchanges between the participants, which indicates that
      future work should focus on the subjects of reflection and transformation. 

PMID- 24310688
TI  - [The translation and cultural adaptation of the Management of Aggression and
      Violence Attitude Scale - MAVAS - for nurses in Brazil].
AB  - This study translated and culturally adapted the Management of Aggression and
      Violence Attitude Scale - MAVAS - for use in Brazil (BR). The methodology
      followed the international guidelines for the cultural adaptation of psychometric
      scales: conceptual equivalence, semantic equivalence, items equivalence, and
      operational equivalence. A group of judges performed a content validity analysis
      that resulted in a 23-item scale divided into four factors with satisfactory
      content validity coefficients (CVCs) for the following parameters: clarity of
      language (CL; 0.88), practical relevance (PR; 0.91), and theoretical relevance
      (TR; 0.92). The data were collected in Londrina, state of Parana, BR in 2011. The
      MAVAS was translated and culturally adapted for use in BR, and the MAVAS-BR
      exhibited satisfactory content validity. Future studies concerning the MAVAS-BR
      are suggested, including the evaluation of psychometric qualities, such as its
      construct validity and reliability. 

PMID- 24310689
TI  - [HIV/aids care according to the perspective of healthcare providers].
AB  - The present study aimed to understand the care provided to patients with HIV/AIDS
      in Portugal according to the healthcare providers' perspective. Thompson's method
      of oral history was used in the study, which included 22 healthcare providers.
      The data were collected by means of semi-structured interviews and were analyzed
      from the narrative compilation perspective formulated by the author using QSR
      Nvivo software. The study complied with the ethical precepts for research. Care
      was analyzed according to three dimensions: cognitive, affective-relational, and
      technical-instrumental. The participants attributed particular relevance to the
      cognitive dimension in association with the moment when the diagnosis of HIV/AIDS
      was established, as well as throughout the course of disease. The affective
      relational dimension was cross-sectional and considered to be valuable throughout
      the course of the disease from its diagnosis to the death of the patients with
      HIV/AIDS. The technical-instrumental dimension was more expressive in the
      advanced stages of the disease, in patients suffering from addiction and in
      terminal illness. As a function of the results, we can conclude that the three
      investigated dimensions are highly relevant for the care of patients with
      HIV/AIDS. 

PMID- 24310690
TI  - [Nursing duties in the basic health unit: perceptions and expectations of nursing
      assistants].
AB  - The present study aimed to analyze the perceptions and expectations regarding
      nursing duties of nursing assistants (NA) working in basic health units (BHUs) in
      a region of the municipality of Sao Paulo. This qualitative study used the
      collective subject discourse (CSD) technique. It took place in three BHUs with 20
      NAs. Data were collected from interviews conducted in 2007. The NAs interviewed
      associated nursing duties with personal attitudes in daily work, seeing the nurse
      as a direct care provider who has the role of advisor and coordinator and who
      performs an excessive number of duties. The expectations of the interviewees were
      the participation of nurses in providing direct care to the user and the power to
      coordinate the team and assess the users' needs. Understanding nursing duties is
      important to respond appropriately to the needs of the community. 

PMID- 24310691
TI  - [Heart failure: expressions of personal knowledge about the disease].
AB  - This qualitative study characterized individuals with heart failure (HF)
      according to their sociodemographic, health, and treatment profiles and analyzed
      their knowledge on the disease and its treatment. A total of 42 volunteers with
      HF were interviewed at a cardiology hospital in Sao Paulo using a semi-structured
      questionnaire; the data were subjected to content analysis. The sample comprised
      mostly males and individuals older than 45 years old; the sample was classified
      as functional class II with associated comorbidities and was subjected to
      pharmacological treatment. The type of knowledge exhibited by the sample was
      illustrative, diagnostic, and explanatory, and many different meanings were
      attributed to the disease. Most volunteers did not know the names, doses, or
      frequencies of use of their medications. Non-pharmacological treatment was
      identified as related to the information provided by the healthcare professionals
      about nutrition and salt and water intake. The results pave the road for
      systematic educational interventions that can improve the coping with and
      management of this disease. 

PMID- 24310692
TI  - [Educative game on drugs for blind individuals: development and assessment].
AB  - Study aimed to develop and assess an educational game on psychoactive drugs
      accessible to blind individuals, conducted in three steps: development of the
      educative game, evaluation by three special education experts, and assessment by
      twelve blind individuals. As a result, a board game called Drugs: staying clean
      was developed. In the Alpha version, experts made suggestions regarding the game
      rules and instructions and the board base, including square texture, game pieces,
      and Braille writing. In Beta version, we proceeded to the assessment by the blind
      participants, who suggested changes in the square texture and the addition of
      Velcro-type material to fix the counters on the board. Then, the Gamma version
      was played by the last pairs of blind players and was considered by them to be
      adequate. In the evaluation of the experts, the game was appropriate, as it
      allowed access to information on psychoactive drugs in a ludic and playful
      manner. 

PMID- 24310693
TI  - [Ethical problems experienced in a supervised curricular internship in nursing in
      an integrated curriculum].
AB  - An exploratory, qualitative study with the objective of analyzing repercussions
      of the supervised curricular internship in the development of the ethical
      dimension of competency in undergraduate nursing students. Semistructured
      interviews were performed with 28 students, professors and nurse preceptors of a
      public institution of higher education in the state of Sao Paulo, during the
      period of October of 2010 to March of 2011. The empirical result was subjected to
      the technique of discourse analysis and resulted in the empirical categories:
      preservation of autonomy; social responsibility and respect in interpersonal
      relations in health care delivery and in the teaching - learning process;
      treatment and care from the ethical dimension; and, public responsibility and
      social justice. It was concluded that the phase that uses problematization as a
      method of teaching and learning provides critical reflection about professional
      practice in the services and system of health. 

PMID- 24310694
TI  - [Profile, competencies and digital fluency of nurses in the Professional
      Improvement Program].
AB  - A descriptive exploratory study conducted in the city of Sao Paulo, which aimed
      to identify the profile, competencies and digital fluency of nurses in the
      Professional Improvement Program in handling technology at work. The population,
      composed by 60 nurses in the program, answered a questionnaire with data about
      profile, digital fluency and professional competencies. The participants were
      found to be: 95.0% female, 61.7% between 23 and 25 years old, 75.0% from public
      schools, 58.3% enrolled in cardiovascular nursing, 98.3% had contact with
      computing resources during graduation, 100.0% had a computer at home, 86.7%
      accessed the internet daily, 96.7% used Messenger and 58.3% had an intermediate
      level of knowledge and skill in computing. Professional competencies required for
      technology management referred to knowing how to be innovative, creative, and
      updated to identify and manage software and to use technological resources. 

PMID- 24310695
TI  - [Evaluation of an educational website on First Aid].
AB  - The aim of this study was to evaluate the structure, quality of information and
      usability of a website on First Aid. The evaluation was performed by information
      technology (IT) and health care professionals and by students, using specific and
      validated instruments. The kappa method was used to evaluate the agreement of the
      answers, and Cronbach's alpha coefficient was used to assess the reliability of
      the instrument. There was no agreement (0.047) among the answers obtained from
      the IT professionals, indicating that the structure of the website must be
      reviewed. There was also no agreement in the evaluation by the health care
      professionals (-0.062); however, the overall positive scores suggest that the
      quality of the information of the website is adequate. The assessment of
      reliability of the instrument to evaluate the navigability rendered a value of
      alpha=0.974. Although improvement of the website structure is recommended, the
      quality of the information is good, and its use has contributed to the
      apprenticeship of students. 

PMID- 24310696
TI  - [Proposal for recognition of the comfort pattern in clients with pemphigus
      vulgaris using Fuzzy Logic].
AB  - The objective was to propose the use of Fuzzy Logic for recognition of comfort
      patterns in people undergoing a technology of nursing care because of pemphigus
      vulgaris, a rare mucocutaneous disease that affects mainly adults. The proposal
      applied experimental methods, with subjects undergoing a qualitative-quantitative
      comparison (taxonomy/relevance) of the comfort patterns before and after the
      intervention. A record of a chromatic scale corresponding to the intensity of
      each attribute was required: pain, mobility and impaired self-image. The Fuzzy
      rules established by an inference engine set the standard for comfort in maximum,
      median and minimum discomfort, reflecting the effectiveness of nursing care.
      Although rarely used in the area of nursing, this logic enabled viable research
      without a priori scaling of the number of subjects depending on the estimation of
      population parameters. It is expected to evaluate the pattern of comfort in the
      client with pemphigus, before the applied technology, in a personalized way,
      leading to a comprehensive evaluation.

PMID- 24310697
TI  - [Construction of terminology subsets: contributions to clinical nursing
      practice].
AB  - The International Classification for Nursing Practice (ICNP(r)) is a
      classification system that unifies the elements of nursing practice (diagnoses,
      interventions and outcomes), enabling elucidation of elements of a specific
      nursing language through the construction of terminology subsets. In this
      reflective essay, aspects relevant to the construction of ICNP(r) terminology
      subsets are highlighted, as well as their contributions to clinical nursing
      practice. The development of subsets as a tool that contributes to making nursing
      language universal, facilitates the communication process, as well as the
      scientific and technological advancement of the profession, is discussed.
      Therefore, its use by nurses worldwide is encouraged. 

PMID- 24310698
TI  - [Economic cost of treating pressure ulcers: a theoretical approach].
AB  - The present study consisted of a theoretical approach to the problem posed by the
      economic costs associated with pressure ulcers (PUs). The initial aim was to
      assess the target problem from a conceptual perspective and then to report the
      results of prevalence studies that formed the basis for investigations of the
      disease's economic impact. The purpose of the present article is to discuss the
      economic costs associated with PUs from both the global point of view (appraising
      their financial repercussion) and the individual point of view (addressing the
      intangible costs). Regarding the economic impact of the costs associated with
      PUs, the total cost of treatment per healthcare setting was estimated relative to
      the Autonomous Community of Azores. The total cost of all the PU categories was
      EUR 7,086,415 in the homecare setting, EUR 1,723,509 in the hospital setting, and
      EUR 1,002,562 in older people's homes. Therefore, the estimated total treatment
      cost of all the PU categories was approximately EUR 9,812,486 in Azores. However,
      the emotional impact of this disease imposes high costs on patients and their
      relatives as a function of the resultant suffering. Indeed, PUs impose high costs
      not only related to the treatment but also related to the intangible costs of the
      suffering caused to patients and their caregivers. 

PMID- 24310699
TI  - [Interprofessional education: training for healthcare professionals for teamwork
      focusing on users].
AB  - The theoretical constructs of interprofessional education (IPE) are analyzed
      based on two reviews of the literature, taking the context of training for
      healthcare professionals in Brazil into consideration. Three types of training
      are identified: uniprofessional, multiprofessional and interprofessional, with
      predominance of the first type. The first occurs among students of the same
      profession, in isolation; the second occurs among students of two or more
      professions, in parallel without interaction; and the third involves shared
      learning, with interaction between students and/or professionals from different
      fields. The distinction between interprofessionalism and interdisciplinarity is
      highlighted: these refer to integration, respectively, of professional practices
      and disciplines or fields of knowledge. Through the analysis presented, it is
      concluded that in the Brazilian context, IPE (the basis for collaborative
      teamwork) is still limited to some recent initiatives, which deserve to be
      investigated. 

PMID- 24310700
TI  - [Nurses' social representations of work-related stress in an emergency room].
AB  - The aim of this study was to understand the social representations of nurses in
      the emergency room and their relationship to stress. This descriptive,
      exploratory study was performed using a qualitative approach, with Social
      Representations Theory being the prime focus. Research was conducted at a
      benchmark public hospital for emergency services in the municipality of Natal/RN.
      The sample consisted of 10 nurses. A content analysis approach was used for data
      analysis. The results indicate that the relationship between nurses' social
      representations of work and stress is a complex and multi-faceted phenomenon that
      contributes to the development of physical, emotional and mental illnesses, and
      exhaustion. 

PMID- 24310701
TI  - [Nursing contributions to the development of the Brazilian Telehealth Lactation
      Support Program].
AB  - The National Telehealth Program was founded by the Ministry of Health, in
      partnership with the Ministry of Education (Ministerio da Educacao - MEC) and the
      Ministry of Science and Technology (Ministerio da Ciencia e Tecnologia - MCT), to
      support the development of family healthcare teams throughout the country. The
      Sao Paulo Telehealth Center has developed the Telehealth Lactation Support
      program, which provides primary healthcare professionals with information on
      diverse aspects of breastfeeding. This paper reports the development of the
      Lactation Support program and the nursing contributions. Project methodology
      included the formation of a multidisciplinary group of pediatricians, nurses,
      speech and language therapists, nutritionists, and dentists. Multimedia teaching
      resources were prepared for inclusion in the Cybertutor platform. Telehealth
      Lactation Support is an innovative and promising addition to continuing education
      for healthcare professionals and provides a framework for the development of
      other programs. 

PMID- 24310702
TI  - [Acquiring nursing knowledge through the constructivist method].
AB  - This article reflects on Vygotsky's theory of knowledge construction by nursing
      professionals. In the Vygotskian approach, persons are seen as agents who
      transform and are transformed by the social relationships of a particular
      culture, or more specifically by the life-long dialectical interaction of human
      beings and their social and cultural environments. The theory of constructivism
      seeks to explain the modification of an individual's knowledge strategy
      throughout his or her life. The constructivist ideas advocated by Vygotsky may
      represent an alternative method for theoretical and practical health studies,
      particularly in relation to the subjective dimension of nursing staff collective
      work. 

PMID- 24310703
TI  - Barriers to clinical trial participation: a comparison of rural and urban
      communities in South Carolina.
AB  - Analyzing data from a telephone survey of rural and urban residents in South
      Carolina, this study attempts to understand how to better promote clinical trials
      (CTs) in rural areas. To explore why participation is lower among the rural
      population, we examine two groups of potential barriers: structural and
      procedural barriers (limited accessibility, lack of awareness, lack of health
      insurance) and cognitive and psychological barriers (lack of knowledge,
      misperceptions, distrust, fear). We then make a series of comparisons between
      rural and urban residents to see whether rural residents are significantly
      different from urban residents in terms of structural/procedural and
      cognitive/psychological barriers they are facing. Findings indicate that there
      are no significant differences between rural and urban residents in their
      willingness to participate in a CT. However, rural residents were more likely to
      perceive limited access to CT sites and lack of awareness of available trials.
      Rural residents also indicated greater lack of knowledge about CTs. Finally, we
      found that distrust and fear were important barriers in shaping one's willingness
      to participate in a CT. Implications of the findings are discussed in detail. 

PMID- 24310704
TI  - Evaluating local policy adoption campaigns in California: Tobacco Retail License
      (TRL) adoption.
AB  - As part of its state-wide "denormalization" campaign, the California Tobacco
      Control Program has funded local tobacco control projects to secure tobacco
      retail licenses (TRLs) in their communities. TRL policies generate funding by
      requiring tobacco retailers within a jurisdiction to obtain a license, which is
      in addition to the state license that tobacco retailers are legally required to
      purchase to sell tobacco products. The funding provided by TRLs enables local law
      enforcement to carry out inspection and enforcement operations. This paper
      examines the unique processes by which local project campaigns attempt to get TRL
      policies adopted in communities across the State of California. Twenty-two local
      projects submitted final evaluation reports pertaining to the adoption of TRLs,
      and the reports from these projects form the basis of the analysis. Successful
      campaigns tended to include the following strategies: (1) determining policy
      readiness; (2) gathering local data; (3) identifying and working with a
      "champion"; (4) building relationships with local law enforcement agencies and
      decision makers; and (5) educating community and decision makers. The major
      challenges faced by local projects included budget cuts and staffing issues,
      concern about creating an unfavorable environment for business by imposing more
      regulations and fees, and complaints about using law enforcement resources for
      tobacco control in light of more "pressing" public safety issues. These
      challenges proved difficult for local projects to overcome, and also highlight
      the need for projects to create and carry out strong but flexible tactical plans
      that incorporate the aforementioned strategies. 

PMID- 24310706
TI  - Hopeful for health care 2014: moving toward affordable health care.

PMID- 24310705
TI  - Monocytes in sterile inflammation: recruitment and functional consequences.
AB  - Monocytes play an important role in initiating innate immune responses. Three
      subsets of these cells have been defined in mice including classical,
      nonclassical and intermediate monocytes. Each of these cell types has been
      extensively studied for their role in infectious diseases. However, their role in
      sterile injury as occurs during ischemia-reperfusion injury, atherosclerosis, and
      trauma has only recently been the focus of investigations. Here, we review
      mechanisms of monocyte recruitment to sites of sterile injury, their modes of
      action, and their effect on disease outcome in murine models with some references
      to human studies. Therapeutic strategies to target these cells must be developed
      with caution since each monocyte subset is capable of mediating either anti- or
      pro-inflammatory effects depending on the setting.

PMID- 24310707
TI  - Alarm fatigue: a roadmap for mitigating the cacophony of beeps.
AB  - The phenomenon known as alarm fatigue is the direct result of excessive alarms in
      hospitals. This article highlights the effects of alarm fatigue and reviews
      current clinical recommendations and guidelines to raise nurse awareness and
      provide tools to combat the problem. 

PMID- 24310708
TI  - A review of the literature: differences in outcomes for uninsured versus insured
      critically ill patients: opportunities and challenges for critical care nurses as
      the Patient Protection and Affordable Care Act begins open enrollment for all
      Americans.
AB  - The US health care system stands alone in its uniqueness compared with other
      industrialized nations. Unlike other developed nations, the United States does
      not provide universal health care coverage to its citizens. America relies
      primarily on private health insurance, allowing for protection against the high
      cost of illness. Because of the economic recession, many Americans cannot afford
      to pay for private health insurance. Contemporary nursing research is reviewing
      the question "Is there is a difference in patient outcomes for the critically ill
      depending upon whether or not they have private health insurance?" By using the
      Johns Hopkins Nursing Evidence-Based Practice Model (Johns Hopkins Nursing
      Evidenced-Based Practice Model and Guidelines. 2nd ed. Indianapolis, IN: Sigma
      Theta Tau International; 2012), 6 articles (level III and IV) were reviewed and
      summarized. After reviewing all the evidence, it is apparent that there are
      poorer patient outcomes, more specifically death in the critically ill patient
      population, if the patient does not have private health insurance. Current
      recommendations from these studies support the Patient Protection and Affordable
      Care Act (http://www.ehealthinsurance.com), which will take effect in 2014 and
      will enable uninsured individuals to have access to medical insurance. This
      provision can also improve preventative care and overall patient outcomes. This
      article has implications for the critical care nurse in the following ways:
      First, it will help the nurse to interpret the implications of the Patient
      Protection and Affordable Care Act and how it will impact critical care practice;
      second, it validates the challenges that uninsured patients present to acute
      health care facilities as they come with more complications and consequently are
      at greater risk for complications; third, it magnifies that the critical care
      nurse may see millions of new patients; and fourth, it demonstrates for the
      critical care nurse how to use the Johns Hopkins Nursing Evidence-Based Practice
      Model to answer questions. 

PMID- 24310710
TI  - Development of a hospital reiki training program: training volunteers to provide
      reiki to patients, families, and staff in the acute care setting.
AB  - Creating a healing and healthy environment for patients, families, and staff is
      an ongoing challenge. As part of our hospital's Integrative Care Program, a Reiki
      Volunteer Program has helped to foster a caring and healing environment,
      providing a means for patients, family, and staff to reduce pain and anxiety and
      improve their ability to relax and be present. Because direct care providers
      manage multiple and competing needs at any given time, they may not be available
      to provide Reiki when it is needed. This program demonstrates that a volunteer
      based program can successfully support nurses in meeting patient, family, and
      staff demand for Reiki services. 

PMID- 24310712
TI  - Hoping for the best, preparing for the worst: strategies to promote honesty and
      prevent medical futility at end-of-life.
AB  - Critical care nurses frequently care for patients nearing end of life. Associated
      advance care planning is often not introduced as early as it needs to be, and
      nurses can help to stimulate a culture change by initiating honest discussions
      about end-of-life treatment options. The Physician Orders for Life-Sustaining
      Treatment form can provide a framework for honesty and information sharing at end
      of life. This article discusses the use of the Physician Orders for Life
      Sustaining Treatment form as an end-of-life care planning tool as well as
      evidence-based communication strategies that promote honest, effective end-of
      life conversations. 

PMID- 24310714
TI  - A call to action: nursing education must embrace change and move forward.
AB  - Nursing and medical educators are challenged by the education-practice gap and
      look for ways to smooth the transition and prepare our graduates for practice.
      Clinical practitioners believe that education does not keep pace with the demands
      in the clinical setting. This article highlights educational challenges, and
      where relevant-will compare and contrast these challenges in nursing education
      with those taking place in medical education and will present creative admission
      requirements and teaching strategies. 

PMID- 24310715
TI  - The effect of intensive care unit environments on nurse perceptions of family
      presence during resuscitation and invasive procedures.
AB  - BACKGROUND: In a growing number of requests, family members are asking for
      proximity to their family member during resuscitation and invasive procedures.
      OBJECTIVES: The objective of this study was to measure the impact of intensive
      care unit environments on nurse perception of family presence during
      resuscitation and invasive procedures. RESEARCH METHODS: The study used a
      descriptive survey design with nurses from 9 intensive care units using the
      Family Presence Self-confidence Scale for resuscitation/invasive procedures that
      measures nurses' perception of self-confidence and Family Presence Risk-Benefit
      Scale for resuscitation and invasive procedures that measures nurses' perception
      of risks/benefits related to managing resuscitation and invasive procedures with
      family present. RESULTS: There were 207 nurses who responded: 14 male and 184
      female nurses (9 missing data), with mean age of 41 +/- 11 years, with a mean of
      15 years in critical care practice. The environments were defined as surgical (n
      = 68), medical (n = 43), pediatric/neonatal (n = 34), and mixed adult
      medical/surgical (n = 36) intensive care units. There were significant
      differences in self-confidence, with medical and pediatric intensive care unit
      nurses rating more self-confidence for family presence during resuscitation (F =
      7.73, P < .000) and invasive procedures (F = 6.41, P < .000). There were
      significant differences in risks/benefits with medical and pediatric intensive
      care unit nurses rating lower risk and higher benefit for resuscitation (F =
      7.73, P < .000). DISCUSSION: Perceptions of family presence were significantly
      higher for pediatric and medical intensive care unit nurses. Further education
      and support may be needed in the surgical and mixed intensive care units.
      Evidence-based practice guidelines that are family centered can define the
      procedures and resources for family presence, to ultimately promote professional
      practice.

PMID- 24310718
TI  - New year resolution: embracing change and welcoming new ways of caring for our
      patients.

PMID- 24310720
TI  - Reply: To PMID 24002804.

PMID- 24310719
TI  - Coregulation of host-response genes in integument: switchover of gene expression
      correlation pattern and impaired immune responses induced by dipteran parasite
      infection in the silkworm, Bombyx mori.
AB  - The activation of host response proteins against parasitic infection is dependent
      on the coregulation of immune gene expression. The infection of commercially
      important silkworm Bombyx mori through endoparasite Exorista bombycis enhanced
      host-response gene expression in integument early in the infection and was
      lowered asymptotically. Principal component analysis (PCA) showed heterogeneity
      while explaining ~80 % variance among expression timings. PCA showed positive and
      negative correlation with gene expression and differentiated transcriptional
      timings, and revealed cross talk within the immune system. Pearson correlation
      analysis showed significant linear correlation (mean R (2) = >0.7; P < 0.004)
      between the expression of 16 pairs of genes in control, while the relation
      switched over to curvilinear due to parasitism. The genes showed pleiotropic
      interaction among them, with four genes each for prophenoloxidase activating
      enzyme (PPAE) and caspase. Besides, after parasitism, exclusive correlation of
      five gene pairs including PPAE-Spatzle pair (R (2) = 0.9; P < 0.011) was observed
      in the integument. In integument, the phenol oxidase (PO) activity showed a
      positive correlation with the tyrosine level (R (2) = 0.410; P < 0.002) and a
      curvilinear relation (R (2) = 0.745; P < 0.0002) with the expanding lysis area.
      The PO activity was positively correlated with BmToll expression and negatively
      correlated with paralytical peptide expression, revealing polygenic influence.
      Caspase expression was tightly regulated by signal genes in control integument,
      whereas they were deregulated after infection. Switchover from linear to
      curvilinear correlation and the appearance of new gene correlations in
      parasitized integument revealed deviation from gene coregulation, leading to
      impaired immune responses, characterized by lowered gene expression and varied
      phenotypic consequences. 

PMID- 24310721
TI  - Synthesis and evaluation of (13)N-labelled azo compounds for beta-amyloid imaging
      in mice.
AB  - PURPOSE: The aim of the present study was to develop short half-lived tools for
      in vitro and in vivo beta-amyloid imaging in mice, for which no suitable PET
      tracers are available. PROCEDURES: Five (13)N-labelled azo compounds (1-5) were
      synthesized using a three-step process using cyclotron-produced [(13)N]NO3 (-).
      Biodistribution studies were performed using positron emission tomography
      computed tomography (PET-CT) on 20-month-old healthy, wild-type (WT) mice. In
      vivo and in vitro binding assays were performed using PET-CT and autoradiography,
      respectively, on 20-month-old healthy (WT) mice and transgenic (Tg2576)
      Alzheimer's disease model mice. RESULTS: (13)N-labelled azo compounds were
      prepared with decay corrected radiochemical yields in the range 27 +/- 4 % to 39
      +/- 4 %. Biodistribution studies showed good blood-brain barrier penetration for
      compounds 1 and 3-5; good clearance data were also obtained for compounds 1-3 and
      5. Compounds 2, 3 and 5 (but not 1) showed a significant uptake in beta-amyloid
      rich structures when assayed in in vitro autoradiographic studies. PET studies
      showed significant uptake of compounds 2 and 3 in the cortex of transgenic
      animals that exhibit beta-amyloid deposits. CONCLUSIONS: The results underscore
      the potential of compounds 2 and 3 as in vitro and in vivo markers for beta
      amyloid in animal models of Alzheimer's disease.

PMID- 24310722
TI  - Radiolabeled RGD tracer kinetics annotates differential alphavbeta 3 integrin
      expression linked to cell intrinsic and vessel expression.
AB  - PURPOSE: The purpose of this paper is to study the association between RGD
      binding kinetics and alphavbeta3 integrin receptor density in the complex tumor
      milieu. PROCEDURES: We assessed alphavbeta3 in vitro and by (68)Ga-DOTA
      [c(RGDfK)]2 positron emission tomography (PET) in tumors with varying
      alphavbeta3. RESULTS: Intrinsic alphavbeta3 expression decreased in the order of
      M21 >>> MDA-MB-231 > M21L in cells. Tumor volume of distribution by PET, V T, was
      significantly higher in M21 compared to isogenic M21L tumors (0.40 +/- 0.01
      versus 0.25 +/- 0.02; p < 0.01) despite similar microvessel density (MVD) likely
      due to higher alphavbeta3. V T for MDA-MB-231 (0.40 +/- 0.04) was comparable to
      M21 despite lower alphavbeta3 but in keeping with the higher MVD, suggesting
      superior tracer distribution. CONCLUSIONS: This study demonstrates that
      radioligand binding kinetics of PET data can be used to discriminate tumors with
      different alphavbeta3 integrin expression-a key component of the angiogenesis
      phenotype-in vivo.

PMID- 24310723
TI  - Inhibition of ATP citrate lyase induces triglyceride accumulation with altered
      fatty acid composition in cancer cells.
AB  - De novo lipogenesis is activated in most cancers and several lipogenic enzymes
      have been implicated as therapeutic targets. Here, we demonstrate a novel
      function of the lipogenic enzyme, ATP citrate lyase (ACLY), in lipid metabolism
      in cancer cells. ACLY depletion by small interfering RNAs caused growth
      suppression and/or apoptosis in a subset of cancer cell lines. To investigate the
      effect of ACLY inhibition on lipid metabolism, metabolome and transcriptome
      analysis was performed. ACLY depletion blocks the fatty acid chain elongation
      from C16 to C18 in triglyceride (TG), but not in other lipid classes. Meanwhile,
      wild-type ACLY overexpression enhanced fatty acid elongation of TG, whereas an
      inactive mutant ACLY did not change it. ACLY depletion-mediated blockade of fatty
      acid elongation was coincident with downregulation of long-chain fatty acid
      elongase ELOVL6, which resides in endoplasmic reticulum (ER). Paradoxically, ACLY
      depletion-mediated growth suppression was associated with TG accumulation. ACLY
      depletion downregulated the expression of carnitine palmitoyltransferase 1A,
      which is a mitochondrial fatty acid transporter. Consistent with this finding,
      metabolome analysis revealed that ACLY positively regulates the carnitine system,
      which plays as an essential cofactor for fatty acid transport across
      mitochondrial membrane. AICAR, an activator of mitochondrial fatty acid oxidation
      (FAO), significantly reduced ACLY depletion-mediated TG accumulation. These data
      indicate that inhibition of ACLY might affect both fatty acid elongation in ER
      and FAO in mitochondria, thereby explaining the TG accumulation with altered
      fatty acid composition. This phenotype may be a hallmark of growth suppression
      mediated by ACLY inhibition. 

PMID- 24310724
TI  - The self-image of physically abused adolescents.
AB  - Thirty physically abused adolescents were compared via the Offer Self-Image
      Questionnaire to thirty nonabused adolescents who were from a similar background.
      Another control group was comprised of normal adolescents tested by Offer,
      Ostrov, and Howard (1981). Results showed that physically abused adolescents feel
      worse in a number of areas when compared to nonabused adolescents. These areas
      include family relations, emotional stability, psychopathology, impulse control,
      coping skills, as well as poorer overall self-image. Implications are drawn for
      the professional's treatment of abused children and their responsibility to
      report abuse. 

PMID- 24310725
TI  - Corporal punishment: Normative data and sociological and psychological correlates
      in a community college population.
AB  - Community college students (N=170) were surveyed regarding the intensity and
      frequency of methods of corporal punishment they have received and the persons
      administering the punishment. Results indicate that corporal punishment is a
      normatively used method of behavioral management. Males reported receiving a
      greater amount of corporal punishment, especially from their fathers. Overall,
      those who received a high amount of corporal punishment reported lower grades and
      a significantly greater number of problems, such as aggression, delinquency,
      depression, and anxiety. These findings are cause for concern and intervention. 

PMID- 24310726
TI  - A cross-cultural comparison of sociopsychological factors in alcohol use among
      adolescents in Israel, France, and the United States.
AB  - The correlates of alcohol use by adolescents are compared in three cultures with
      different prevalences of alcohol use: France, with high prevalence; Israel, with
      low prevalence; and the United States, in the middle. In all three countries,
      significant others, parents and peers, are more powerful predictors of alcohol
      use than are the adolescent's personal attributes, such as attitudes, behaviors,
      and demographic characteristics. Cross-cultural differences appear in the
      relative importance of parents and peers and in the structure of influence of
      parents and peers as role models. Parents are more important role models in
      Israel than in the other two cultures, while peers are more important in the
      United States than in France or in Israel. 

PMID- 24310727
TI  - Parent-adolescent separation: The role of parental divorce.
AB  - Previous research has identified Emotional Separation and Personal Control as two
      sets of home leaving indicators that are associated, respectively with relatively
      troubled and relatively untroubled parent-adolescent separation. As expected,
      among late adolescent males, parental divorce was highly related to endorsement
      of Emotional Separation as an important composite indicator of having left home.
      For females, being a firstborn was associated with endorsing Personal Control as
      an important composite indicator of home-leaving. Findings were interpreted as
      supporting previous research which has indicated that males experience more
      adjustment problems after parental divorce than females. 

PMID- 24310728
TI  - The extent and effects of peer pressure among high school students: A
      retrospective analysis.
AB  - Although people assume that peer pressure is an influential component of
      adolescent development, few empirical studies have investigated the nature and
      extent of its influence. Using retrospective accounts from 297 college
      undergraduates, the present study assessed how much pressure peers exerted in
      numerous areas of high school life and how this pressure influenced teenagers'
      attitudes and behaviors. One-third of both genders identified peer pressure as
      one of the hardest things they had to face as a teenager. Generally, however,
      peer pressure appeared stronger for females than males, and the genders disagreed
      about the areas in which pressure was strongest. Perceptions of peer pressure
      were significantly associated with dating attitudes, sexual activity, and use of
      drugs and alcohol, but not with relationships with parents. The findings
      suggested that adolescents may be their own worst enemy in any attempt to break
      away from gender-stereotypic attitudes and behavior. 

PMID- 24310729
TI  - Self-esteem and self-presentation among the young as a function of age and
      gender.
AB  - This study investigated the effect of self-esteem on the tendency to convey a
      false impression to others by hiding one's feelings behind a facade. Utilizing a
      sample of youth (ages 8-19), a multiple regression analysis revealed that the
      lower the self-esteem, the greater the tendency to present a false front. In
      addition, other aspects of the self-concept, including vulnerability to
      criticism, self-consciousness, and the tendency to fantasize affect the tendency
      to present a false front. Furthermore, the nature of the self-esteem/ fabrication
      relationship is a joint function of age and gender. As age increases, the direct
      effect of self-esteem on fabrication loses statistical significance, but this
      loss occurs differently for boys and girls. For boys, the direct effect is
      significant in pre-adolescence (8-11), but not in early or late adolescence (12
      14 and 15-19). For girls, the direct effect is significant in pre- and early
      adolescence (8-11 and 12-14), but not in late adolescence (15-19). Reasons for
      the differing patterns for boys and girls are discussed. 

PMID- 24310730
TI  - The use of children's religious ideas in their psychiatric evaluation.
AB  - Children's religious ideas provide a source of projective material that can be
      relevant clinically in a child's psychiatric evaluation. Areas that are sometimes
      revealed include (1) information about the child's parental introjects; (2) level
      of superego formation; (3) level of defense formation; (4) areas that are most
      anxiety provoking for the child. This religious material is frequently ignored,
      but can be a particularly useful adjunct when the usual child-evaluative
      techniques do not reveal a complete picture. 

PMID- 24310731
TI  - Effects of all-trans retinoic acid, retinol, and beta-carotene on murine
      macrophage activity.
AB  - Previous studies have demonstrated that vitamin A and carotenoids regulate immune
      function in lymphocytes and splenocytes, and that the carotenoid lutein regulates
      matrix metalloproteinase-9 (MMP-9) production in macrophages. In this study, we
      investigated the effects of all-trans retinoic acid (atRA, a bioactive vitamin A
      metabolite), retinol (vitamin A), and beta-carotene (vitamin A precursor) on the
      activity of murine RAW264.7 and peritoneal macrophages. Our results indicated
      that atRA and retinol could induce GM-CSF and IL-16 expression, whereas all these
      tested substances enhanced MMP-9 production. Interestingly, the expression of GM
      CSF, IL-16, and MMP-9 was distinctly regulated by these three substances. AtRA
      and retinol affected GM-CSF and IL-16 expression mainly through RA receptor beta
      (RARbeta). However, atRA induced MMP-9 production was via RARalpha activation and
      retinol and beta-carotene caused MMP-9 production via RARalpha and beta
      activation. These were supported by the observations that the RARalpha and beta
      agonists/antagonists differentially affected MMP-9 production and that atRA and
      beta-carotene enhanced RARE-mediated and MMP-9 promoter luciferase activity. In
      parallel, while the MMP-9 induction by atRA was not affected by the MAPKs
      inhibitors, its induction by retinol and beta-carotene was repressed by the
      inhibitor targeting ERK1/2. Finally, we show that all the tested substances could
      functionally enhance macrophage phagocytosis. Taken together, we provide evidence
      here for the first time that atRA, retinol, and beta-carotene differentially
      regulate GM-CSF, IL-16, and MMP-9 production in macrophages, explaining at least
      in part why these vitamin A-related substances are beneficial for immunity. 

PMID- 24310732
TI  - Molecular modeling evidence for His438 flip in the mechanism of
      butyrylcholinesterase hysteretic behavior.
AB  - Cholinesterases display a hysteretic behavior with certain substrates and
      irreversible inhibitors. For years, this behavior has remained puzzling. However,
      several lines of evidence indicated that it is caused by perturbation of the
      catalytic triad and its water environment. In the present study, using molecular
      dynamics simulations of Ala328Cys BuChE mutant and wild-type BuChE in the absence
      and presence of a co-solvent (sucrose, glycerol), we provide evidence that
      hysteresis originates in a flip of the catalytic triad histidine (His438). This
      event is controlled by water molecules that interact with active site residues.
      The physiological significance of this phenomenon is still an issue. 

PMID- 24310734
TI  - T-tube in duodenal fistula: reply.

PMID- 24310733
TI  - Comparison of perioperative and long-term outcomes of total and proximal
      gastrectomy for early gastric cancer: a multi-institutional retrospective study.
AB  - BACKGROUND: Various surgical procedures are used to treat early gastric cancers
      in the upper third of the stomach (U-EGCs). However, there is no general
      agreement regarding the optimal surgical procedure. METHODS: The medical records
      of 203 patients with U-EGC were collected from 13 institutions. Surgical
      procedures were classified as Roux-en-Y esophagojejunostomy after total
      gastrectomy (TG-RY), esophagogastrostomy after proximal gastrectomy (PG-EG), or
      jejunal interposition after PG (PG-JI). Patient clinical characteristics and
      perioperative and long-term outcomes were compared among these three groups.
      RESULTS: TG-RY, PG-EG, and PG-JI were performed in 122, 49, and 32 patients,
      respectively. Tumors were larger in TG-RY patients than in PG-EG and PG-JI
      patients, and undifferentiated-type gastric adenocarcinoma tended to be more
      frequent in TG-RY than in PG-EG. The operative time was shorter for PG-EG than
      for PG-JI and TG-RY. Hospital stay and early postoperative complications were not
      different for the three procedures. With respect to gastrectomy-associated
      symptoms, a "stuck feeling" and heartburn tended to be more frequent in PG-EG
      patients, while dumping syndrome and diarrhea were more frequent in TG-RY
      patients. Post-surgical weight loss was not different among the three groups,
      however, serum albumin and hemoglobin levels tended to be lower in TG-RY
      patients. CONCLUSION: Three surgical procedures for U-EGC did not result in
      differences in weight loss, but PG-EG and PG-JI were better than TG-RY according
      to some nutritional markers. In U-EGC, where patients are expected to have long
      survival times, PG-EG and PG-JI should be used rather than TG-RY.

PMID- 24310735
TI  - Two-ventricle repair for complex congenital heart defects palliated towards
      single-ventricle repair.
AB  - OBJECTIVES: Complex congenital heart defects that present earlier in life are
      sometimes channelled towards single-ventricle repair, because of anatomical or
      logistic challenges involved in two-ventricle correction. Given the long-term
      functional and survival advantage, we have been consciously exploring the
      feasibility of a biventricular repair in these patients when they present later
      for Fontan completion. METHODS: Since June 2009, 71 patients were referred for
      staged completion of the Fontan procedure. Following detailed evaluation that
      included three-dimensional echocardiography and magnetic resonance imaging, 10
      patients (Group 1-median age 6 years) were identified and later underwent complex
      biventricular repair with takedown of Glenn shunt, while completion of
      extracardiac Fontan repair was done in 61 patients (Group 2-median age 7 years).
      RESULTS: Two-ventricle repair was accomplished in all the 10 Group 1 patients.
      One patient developed complete heart block requiring permanent pacemaker
      insertion. Late patch dehiscence occurred in another (awaiting repair). At a
      median follow-up of 15 months, there was no mortality among the Group 1 patients
      and all except for 1 patient were symptom free. There were 2 early deaths (3.3%)
      in the Group 2 patients. CONCLUSIONS: Two-ventricular repair, although surgically
      challenging, should be considered in all patients with two functional ventricles
      who come for Fontan completion. Comprehensive preoperative imaging and meticulous
      planning helps in identifying suitable candidates.

PMID- 24310737
TI  - Elevated cerebrospinal fluid and blood concentrations of oxytocin following its
      intranasal administration in humans.
AB  - There has been an unprecedented interest in the modulatory effects of intranasal
      oxytocin on human social cognition and behaviour, however as yet no study has
      actually demonstrated that this modality of administration increases
      concentrations of the peptide in the brain as well as blood in humans. Here using
      combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving
      either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin
      levels significantly increased in both plasma and CSF. However, whereas oxytocin
      plasma concentrations peaked at 15 min after intranasal administration and
      decreased after 75 min, CSF concentrations took up to 75 min to reach a
      significant level. Moreover, there was no correlation (r = <0.10) between
      oxytocin plasma and CSF concentrations. Together, these data provide crucial
      insights into the plasma and CSF kinetics of intranasally administered oxytocin. 

PMID- 24310736
TI  - Activity of the pan-class I phosphoinositide 3-kinase inhibitor NVP-BKM120 in T
      cell acute lymphoblastic leukemia.
AB  - Constitutively active phosphoinositide 3-kinase (PI3K) signaling is a common
      feature of T-cell acute lymphoblastic leukemia (T-ALL), where it upregulates cell
      proliferation, survival and drug resistance. These observations lend compelling
      weight to the application of PI3K inhibitors in the therapy of T-ALL. Here, we
      have analyzed the therapeutic potential of the pan-PI3K inhibitor NVP-BKM120
      (BKM120), an orally bioavailable 2,6-dimorpholino pyrimidine derivative, which
      has entered clinical trials for solid tumors, on both T-ALL cell lines and
      patient samples. BKM120 treatment resulted in G2/M phase cell cycle arrest and
      apoptosis, being cytotoxic to a panel of T-ALL cell lines and patient T
      lymphoblasts, and promoting a dose- and time-dependent dephosphorylation of Akt
      and S6RP. BKM120 maintained its pro-apoptotic activity against Jurkat cells even
      when cocultured with MS-5 stromal cells, which mimic the bone marrow
      microenvironment. Remarkably, BKM120 synergized with chemotherapeutic agents
      currently used for treating T-ALL patients. Moreover, in vivo administration of
      BKM120 to a subcutaneous xenotransplant model of human T-ALL significantly
      delayed tumor growth, thus prolonging survival time. Taken together, our findings
      indicate that BKM120, either alone or in combination with chemotherapeutic drugs,
      may be an efficient treatment for T-ALLs that have aberrant upregulation of the
      PI3K signaling pathway. 

PMID- 24310738
TI  - Discrepancy between endoscopic forceps biopsy and endoscopic resection in gastric
      epithelial neoplasia.
AB  - BACKGROUND: Endoscopic forceps biopsy (EFB) is a major diagnostic procedure for
      gastric epithelial neoplasia (GEN). However, discrepancy between the result of
      EFB and endoscopic resection (ER) is not uncommon. Thus, there is controversy
      over whether specimens obtained by EFB are optimal for diagnosis of GEN. We
      investigated the discrepancy between EFB and ER in the diagnosis of GEN. METHODS:
      A total of 1,850 GEN cases were histologically diagnosed with EFB, including 954
      low-grade dysplasias (LGDs), 315 high-grade dysplasias (HGDs), and 581
      carcinomas. Following diagnosis with EFB, all patients were treated with ER. We
      retrospectively reviewed the pathologic findings and patient characteristics and
      analyzed predictors for the discrepancy between the two procedures (largest
      diameter, number of biopsy fragments, number of biopsy fragments/largest
      diameter, location, macroscopic type, color, surface unevenness, and erosion).
      RESULTS: The overall discrepancy rate between EFB and ER was 31.7 % (587/1,850).
      Among the discordant group, 440 (23.9 %) cases showed a higher grade of disease
      after ER; 229 of the 954 LGDs (24.0 %) were diagnosed as HGD or carcinoma, 166 of
      the 315 HGDs (52.7 %) as carcinoma, and 45 of the 581 differentiated carcinomas
      (7.7 %) as undifferentiated carcinoma. In the LGD group with EFB, the largest
      diameter (>=1.8 cm; P < 0.001), surface unevenness (P = 0.014), and depressed
      macroscopic type (P < 0.001) were factors associated with discrepancy. In the
      carcinoma group with EFB, flat macroscopic type (P = 0.043) was the only
      significant factor. In the HGD group with EFB, there were no significant factors
      for discrepancy. CONCLUSIONS: EFB can be insufficient for diagnosing GENs, and ER
      can be considered not only as treatment but also as a diagnostic modality in GEN.
      It is especially pertinent to all cases of HGD regardless of their endoscopic
      features and to cases of LGDs with the largest lesion diameter >=1.8 cm, surface
      unevenness, or a depressed macroscopic type.

PMID- 24310739
TI  - The composition of surgical teams in the operating room and its impact on
      surgical team performance in China.
AB  - BACKGROUND: Previous studies on surgical team composition have shown that
      surgical team size had an independent impact on surgical performance in US and
      Canadian hospitals. We aimed to investigate the impact of team composition on
      surgical performance in two Chinese hospitals. METHODS: General surgery
      procedures performed from April 2011 to June 2012 were retrospectively reviewed
      to record the number of attendees in the operating room (OR) and the procedure
      time (PT). RESULTS: A total of 1,900 valid procedures, mostly laparoscopic, were
      performed during the study period. The mean PT was 90.5 min. On average, there
      were a total of 6 (range = 3-8) team members per procedure: 3 (range = 1-5)
      surgeons, 2 nurses, and 1 anesthesiologist. Unlike the data reported for the US
      and Canada, the number of nurses and anesthesiologists remained stable in most
      cases, whereas the number of surgeons differed by procedure. Multiple-regression
      analysis revealed that both the complexity of the operation and the team size
      significantly affected PT. When procedure complexity and patient condition were
      kept constant, adding one team member in our data analysis predicted an increase
      of 34.7 min in the PT. CONCLUSION: The surgical team size has a measurable effect
      on PT. Aside from surgical complexity, the team composition and member stability
      affected PT in the OR. Optimizing surgical teams and developing a strategy to
      maintain team stability are of great importance for improving OR efficiency.

PMID- 24310741
TI  - Mobile phone messaging reminders for attendance at healthcare appointments.
AB  - BACKGROUND: This review is an update of the original Cochrane review published in
      July 2012. Missed appointments are a major cause of inefficiency in healthcare
      delivery with substantial monetary costs for the health system, leading to delays
      in diagnosis and appropriate treatment. Patients' forgetfulness is one of the
      main reasons for missed appointments. Patient reminders may help reduce missed
      appointments. Modes of communicating reminders for appointments to patients
      include face-to-face communication, postal messages, calls to landlines or mobile
      phones, and mobile phone messaging. Mobile phone messaging applications, such as
      Short Message Service (SMS) and Multimedia Message Service (MMS), could provide
      an important, inexpensive delivery medium for reminders for healthcare
      appointments. OBJECTIVES: To update our review assessing the effects of mobile
      phone messaging reminders for attendance at healthcare appointments. Secondary
      objectives include assessment of costs; health outcomes; patients' and healthcare
      providers' evaluation of the intervention and perceptions of safety; and possible
      harms and adverse effects associated with the intervention. SEARCH METHODS:
      Original searches were run in June 2009. For this update, we searched the
      Cochrane Central Register of Controlled Trials (CENTRAL,The Cochrane Library
      2012, Issue 8), MEDLINE (OvidSP) (January 1993 to August 2012), EMBASE (OvidSP)
      (January 1993 to August 2012), PsycINFO (OvidSP) (January 1993 to August 2012)
      and CINAHL (EbscoHOST) (January 1993 to August 2012). We also reviewed grey
      literature (including trial registers) and reference lists of articles. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) assessing mobile phone messaging as
      reminders for healthcare appointments. We only included studies in which it was
      possible to assess effects of mobile phone messaging independent of other
      technologies or interventions.   DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed all studies against the inclusion criteria, with any
      disagreements resolved by a third review author. Study design features,
      characteristics of target populations, interventions and controls, and results
      data were extracted by two review authors and confirmed by a third author. Two
      authors assessed the risk of bias of the included studies. As the intervention
      characteristics and outcome measures were similar across included studies, we
      conducted a meta-analysis to estimate an overall effect size. MAIN RESULTS: We
      included eight randomised controlled trials involving 6615 participants. Four of
      these studies were newly identified during this update.We found moderate quality
      evidence from seven studies (5841 participants) that mobile text message
      reminders improved the rate of attendance at healthcare appointments compared to
      no reminders (risk ratio (RR) 1.14 (95% confidence interval (CI) 1.03 to 1.26)).
      There was also moderate quality evidence from three studies (2509 participants)
      that mobile text message reminders had a similar impact to phone call reminders
      (RR 0.99 (95% CI 0.95 to 1.02). Low quality evidence from one study (291
      participants) suggests that mobile text message reminders combined with postal
      reminders improved the rate of attendance at healthcare appointments compared to
      postal reminders alone (RR 1.10 (95% CI 1.02 to 1.19)). Overall, the attendance
      to appointment rates were 67.8% for the no reminders group, 78.6% for the mobile
      phone messaging reminders group and 80.3% for the phone call reminders group. One
      study reported generally that there were no adverse effects during the study
      period; none of the studies reported in detail on specific adverse events such as
      loss of privacy, data misinterpretation, or message delivery failure. Two studies
      reported that the costs per text message per attendance were respectively 55% and
      65% lower than costs per phone call reminder. The studies included in the review
      did not report on health outcomes or people's perceptions of safety related to
      receiving reminders by text message. AUTHORS' CONCLUSIONS: Low to moderate
      quality evidence included in this review shows that mobile phone text messaging
      reminders increase attendance at healthcare appointments compared to no
      reminders, or postal reminders.Text messaging reminders were similar to telephone
      reminders in terms of their effect on attendance rates, and cost less than
      telephone reminders. However, the included studies were heterogeneous and the
      quality of the evidence therein is low to moderate. Further, there is a lack of
      information about health effects, adverse effects and harms, user evaluation of
      the intervention and user perceptions of its safety. The current evidence
      therefore still remains insufficient to conclusively inform policy
      decisions.There is a need for more high-quality randomised trials of mobile phone
      messaging reminders, that measure not only patients' attendance rates, but also
      focus on the cost-effectiveness of these interventions. Health outcomes,
      patients' and healthcare providers' evaluation and perceptions of the safety of
      the interventions, potential harms, and adverse effects of mobile phone messaging
      reminders should be assessed. Studies should report message content and timing in
      relation to the appointment.

PMID- 24310740
TI  - Medically refractory gastroesophageal reflux disease in the obese: what is the
      best surgical approach?
AB  - BACKGROUND: Obesity is a recognized risk factor for gastroesophageal reflux
      disease (GERD). Traditional antireflux surgery (fundoplication) may not be
      appropriate in the morbidly obese, especially when other effective alternatives
      exist (bariatric surgery). METHODS: A 13-item survey was designed to elicit
      professional opinions regarding the treatment of medically refractory GERD in
      obese patients. Members of the Society of American Gastrointestinal and
      Endoscopic Surgeons (SAGES) were randomly selected and emailed a link to an
      online survey. RESULTS: A total of 550 surgeons were contacted via email, and 92
      (17 %) completed the survey. Of the respondents, 88 % perform laparoscopic
      antireflux surgery, 63 % perform bariatric surgery, and 59 % perform both.
      Overall, 77 % completed a minimally invasive surgery fellowship. In response to
      the question "Would you perform a laparoscopic fundoplication in a patient with
      medically refractory GERD and a BMI of 'X'?" surgeons were less likely to offer
      fundoplication at a higher body mass index (BMI). The majority of respondents
      felt that laparoscopic Roux-en-Y gastric bypass was the best option (91 %),
      followed by laparoscopic sleeve gastrectomy (6 %). Many had a morbidly obese
      patient with a primary surgical indication of GERD denied a bariatric procedure
      by their insurance company (57 %), and 35 % of those surgeons chose to do nothing
      rather than subject the patient to a fundoplication. Respondents uniformly felt
      that bariatric surgery should be recognized as a standard surgical option for
      treating GERD in the obese (96 %). CONCLUSION: When surgical treatment of GERD is
      indicated in an obese patient, bariatric surgery is the optimal approach, in the
      opinion of surgeons responding to our survey. Unfortunately, third-party payers
      often decline to provide benefits for a bariatric procedure for this indication.
      Additional data is necessary to confirm our belief that the opinions elicited
      through this survey are consistent with the standard of care as defined by the
      medical community.

PMID- 24310742
TI  - Distribution of transfer RNA genes in thePisum sativum chloroplast DNA.
AB  - Purified chloroplast tRNAs were isolated fromPisum sativum leaves and
      radioactively labeled at their 3' end using tRNA nucleotidyl transferase and
      alpha(32)P-labeled CTP. Pea ctDNA was fragmented using a number of restriction
      endonucleases and hybridized with thein vitro labeled chloroplast tRNAs by DNA
      transfer method. Genes for tRNAs have been found to be dispersed throughout the
      chloroplast genome. A closer analysis of the several hybrid regions using
      recombinant DNA plasmids have shown that tRNA genes are localized in the
      chloroplast genome in both single and multiple arrangements. Two dimensional gel
      electrophoresis of total ct tRNA have identified 36 spots. All of them have been
      found to hybridize withPisum sativum ctDNA. Using recombinant clones, 30 of the
      tRNA spots have been mapped inPisum sativum ctDNA. 

PMID- 24310743
TI  - The disease resistance response in pea is associated with increased levels of
      specific mRNAs.
AB  - A cDNA library was constructed using poly(A)(+)RNA fromPisum sativum which had
      been treated for 8 h with the fungusFusarium solani f. sp.phaseoli. Two thousand
      four hundred recombinant colonies were screened by differential colony
      hybridization using(32)P-labelled cDNAs prepared from RNA extracted from either
      noninoculated or inoculated pea tissue. cDNA clones were then selected, which
      showed greater hybridization with cDNA prepared from pea RNA 8 h post-inoculation
      than with a cDNA probe from 0 h. Seven distinct hybridization classes were chosen
      for further study. Northern blot analyses of total cellular RNAs inoculated for
      16 h with eitherF. solani phaseoli or water demonstrated that each cDNA clone
      selected represents an mRNA species which increases substantially in abundance
      during infection.Results of(3)H-uridine pulse-labelling experiments suggested
      that enhanced synthesis is at least partially responsible for the accumulation of
      the fungus-inducible mRNAs which hybridized with the clones. 

PMID- 24310744
TI  - Positioning of protein-coding genes on the soybean chloroplast genome.
AB  - Seven major plastid protein encoding genes were positioned on the soybean
      chloroplast DNA by heterologous hybridization. These include the genes for the
      alpha, beta and epsilon subunits of the CF1 component of ATP synthase (atpA, atpB
      and atpE respectively), for subunit III of the CF0 component of ATP synthase
      (atpH), for the cytochrome f (cytF), for the '32 Kd' thylakoid protein (psbA),
      and for the large subunit of ribulose-1,5-bisphosphate carboxylase-oxygenase
      (rbcL), all of which map in the large single copy region. The atpB, atpE and rbcL
      genes are located in the region adjacent to one of the segments of the inverted
      repeat. The genetic organization of the soybean chloroplast DNA is compared to
      that of other plastid genomes. 

PMID- 24310745
TI  - A shoot-specific mRNA from pea: nucleotide sequence and regulation as compared to
      light-induced mRNAs.
AB  - The regulation of a mRNA encoding a shoot-specific polypeptide from developing
      pea seedlings was studied and compared to the regulation of mRNAs encoding two
      major light-induced nuclear-encoded polypeptides, the small subunit of the
      ribulose 1,5 biphosphate carboxylase (ssRuBPCase) and a polypeptide of the light
      harvesting chlorophyll a/b complex (LHCP). By using cDNA clones as probes in
      Northern blottings of total cellular RNA it was found that both ssRuBPCase and
      LHCP mRNA could be induced in shoots by white and red light but to lower levels
      in roots and cotyledons. In contrast, the mRNA for the shoot-specific polypeptide
      was only found in shoots, and was present approximately two days after the start
      of germination. The shoot-specific mRNA sequence was predominantly found in stem
      tissue, irrespective of illumination, both in the young seedlings and adult
      plants. Only very low amounts could be detected in plumule and leaf. The shoot
      specific sequence could also be detected in RNA isolated from developing shoots
      of another pea cultivar but not in those of other legumes and of cereals. The
      primary sequence of the complete coding portion and the deduced amino acid
      sequence of the mRNA encoding the shoot-specific polypeptide was determined. The
      observed codon usage is non-random and is consistent with data from other high
      plant genes. Possible polyadenylation signal sequences (AATAAG and AATAAT) were
      present at 55 and 124 bases 5' of the poly(A) tail. The polypeptide encoded by
      the shoot-specific mRNA consists of 196 amino acids with a calculated molecular
      weight of 21 898. It contains a four times reiterated highly conserved unit of 26
      amino acids. The NH2-terminal end is highly hydrophobic and resembles a signal
      polypeptide. 

PMID- 24310746
TI  - Localization of the gene for apocytochromeb-559 on the plastid chromosome of
      spinach.
AB  - The gene for cytochromeb-559, associated with the photosystem II reaction center,
      has been located on the spinach plastid chromosome by cell-free coupled
      transcription-translation and RNA-programmed hybrid selection translation using
      appropriate recombinant DNAs, RNA fractions, and monospecific antisera. The gene
      is located in the large single-copy segment of the plastid chromosome between the
      genes for cytochomef and the P680 chlorophylla apoprotein of photosystem II and
      transcribed in the opposite direction relative to these genes. The 10 kd protein
      is decoded from a bicistronic 1.0 kb mRNA and is apparently not made as a
      precursor in cell-free rabbit reticulocyte andE. coli lysates. 

PMID- 24310747
TI  - Pathogenesis-related proteins.

PMID- 24310748
TI  - Variable presence of the 1.94kb mitochondrial plasmid in maize S cytoplasm and
      its relationship to cytoplasmic male sterility.
AB  - Mitochondrial DNA (mtDNA) was isolated from over 100 different maize nucleo
      cytoplasmic combinations. DNA preparations were assayed for the presence of the
      1.94kb mitochondrial plasmid by agarose gel electrophoresis and hybridization to
      a recombinant clone of the plasmid. The plasmid was present in all tested inbreds
      which carried N, male fertile, cytoplasm or the cytoplasmically male sterile
      (cms) groups,cms-T andcms-C. However, members of thecms-S group differed with
      respect to the presence of the plasmid. Cytoplasms I, J and S possessed the
      plasmid, whereas cytoplasms B, CA, D, G, H, IA, ME, ML, PS, RD and VG did not.Cms
      S group lines which had spontaneously reverted to fertility (nuclear and
      cytoplasmic revertants) did not exhibit a concomitant change in 1.94kb plasmid
      levels, although all such lines showed the previously reported alteration in
      levels of the linear mtDNAs, S1 and S2. The presence or absence of the plasmid
      was not correlated with (i) frequency of reversion to fertility, (ii) the degree
      of male sterility expressed, (iii) the presence or absence of standard nuclear
      restorer to fertility genes and (iv) nuclear genotype. Latin American races
      carrying RU cytoplasm possessed the plasmid, as did sweet corn varieties. The
      relevance of the data tocms and evolution of thecms-S group is discussed. 

PMID- 24310749
TI  - A variant mitochondrial DNA arrangement specific toPetunia stable sterile somatic
      hybrids.
AB  - We have characterized two related regions of twoPetunia mitochondrial genomes in
      order to understand how plant mt genomes from a cytoplasmic male sterile (cms)
      line and a fertile line diverge from one another. Restriction maps of these
      regions indicate that a sequence arrangement shared by the two genomes adjoins
      sequences which are not shared at the corresponding locations in the two genomes.
      A point where the mt genomes from the cms line and the fertile lines diverge from
      each other was identified and mapped.Previously we had observed that somatic
      hybrids constructed from the cms and the fertile line contained mt genomes
      carrying new combinations of parental mtDNA restriction fragments (3). Using the
      restriction maps of the two related mtDNA regions, a mtDNA arrangement unique to
      the cms parent could be shown to be present in all 17 stable sterile somatic
      hybrids tested and none of the 24 stable fertile somatic hybrids tested. This
      data does not exclude the possibility that additional, as yet unidentified, mtDNA
      arrangements unique to the cms parent might also be found exclusively in sterile
      somatic hybrids. Whether or not the sterile parental mtDNA arrangement reported
      here is functionally related to cms, it apparently segregates with cms in somatic
      hybrids. 

PMID- 24310750
TI  - Cloning of the glutamine synthetase gene fromspirulina platensis.
AB  - An 8 Kilobase-pair (Kbp) HindIII fragment containing the coding sequence
      forSpirulina platensis glutamine synthetase [EC 6.3.1.1.] has been identified
      utilizing a probe derived fromAnabaena 7120 and cloned in the vector pAT153. 

PMID- 24310751
TI  - Intracellular coding sites of polypeptides associated with photosynthetic oxygen
      evolution of photosystem II.
AB  - Three hydrophilic polypeptides of approximately 34, 23, and 16 kd located on the
      inner thylakoid surface are associated with the water-splitting activity of
      photosystem II. Stable transcripts for the three proteins were found only in
      cytosolic (polyadenylated) RNA, suggesting that they are encoded in nuclear
      genes. The immunologically reacting products synthesized in a rabbit reticulocyte
      cell-free translation system are larger in size than the authentic mature
      proteins by about 6-10 kd. These larger precursors are imported post
      translationally into isolated, intact chloroplasts, and are processed to their
      mature forms during or after translocation. The imported proteins can be
      extracted from thylakoids by procedures used to isolate the three native proteins
      of the water-splitting complex, suggesting that they have assembled properly into
      their final destination, the inner thylakoid surface. 

PMID- 24310752
TI  - Rhizobium nodulation genes involved in root hair curling (Hac) are functionally
      conserved.
AB  - Five specific transposon-induced nodulation defective (Nod(-)) mutants from
      different fast-growing species ofRhizobium were used as the recipients for the
      transfer of each of several endogenous Sym(biosis) plasmids or for recombinant
      plasmids that encode early nodulation and host-specificity functions. The Nod(-)
      mutants were derived fromR. trifolii, R. meliloti and from a broad-host
      rangeRhizobium strain which is able to nodulate both cowpea (tropical) legumes
      and the non-legumeParasponia. These mutants had several common features (a), they
      were Nod(-) on all their known plant hosts, (b), they could not induce root hair
      curling (Hac(-)) and (c), the mutations were all located on the endogenous Sym
      plasmid of the respective strain. Transfer to these mutants of Sym plasmids (or
      recombinant plasmids) encoding heterologous information for clover nodulation
      (pBR1AN, pRt032, pRt038), for pea nodulation (pJB5JI, pRL1JI::Tn1831), for
      lucerne nodulation (pRmSL26), or for the nodulation of both tropical legumes and
      non-legumes (pNM4AN), was able to restore root hair curling capacity and in most
      cases, nodulation capacity of the original plant host(s). This demonstrated a
      functional conservation of at least some genes involved in root hair curling.
      Positive hybridization between Nod DNA sequences fromR. trifolii and from a broad
      host-rangeRhizobium strain (ANU240) was obtained to other fast-growingRhizobium
      strains. These results indicate that at least some of the early nodulation
      functions are common in a broad spectrum ofRhizobium strains. 

PMID- 24310753
TI  - HMG-like protein in barley and corn nuclei.
AB  - Chromosomal proteins have been isolated from barley (Hordeum vulgare) and corn
      (Zea mays) nuclei by extraction with 5% perchloric acid. In each plant, one
      protein was shown to belong to the HMG proteins. Their molecular weights are very
      close to that of HMG 14 from chicken erythrocytes, as shown by electrophoretic
      mobility in SDS polyacrylamide gels. In acetic acid-urea-Triton polyacrylamide
      gels they migrate between HMG 1,2 and HMG 14, from chicken erythrocytes. Their
      amino acid compositions are typical of HMG proteins, with equivalent high values
      of acidic and basic residues.Extraction of HMG's from purified barley chromatin
      fractions with 0.35 M NaCl considerably reduces histone H2 contamination and
      increases the yield of HMG up to 0.7% of the total histones. In this technique a
      second protein was extracted which is soluble in 2% Trichloroacetic acid and
      shows electrophoretic mobility analogous to those of HMG 14 and 17 from chicken
      erythrocytes. Whether or not these proteins are counterparts of the animal HMG's
      1-2 or HMG's 14-17 is discussed. 

PMID- 24310754
TI  - Characterization of the mRNA transcripts of the maize, ribulose-1,5-bisphosphate
      carboxylase, large subunit gene.
AB  - The analysis of RNA isolated from maize leaves indicates that there are two mRNA
      transcripts which are homologous to the chloroplast encoded gene for the large
      subunit of ribulose-1,5-bisphosphate carboxylase (rbcL). The 5' end of the
      smaller transcript, 1.62 Kb in length, begins at a position which is 60
      nucleotides upstream from the coding sequence of the gene, corresponding to the
      position mapped by earlier workers. The larger transcript, 1.86 Kb in length, has
      not been previously described and originates from a site on the gene which is 302
      nucleotides upstream from the coding sequence. The increased size of the
      largerbcL mRNA transcript from maize, as compared to the transcripts from spinach
      and tobacco, results from the presence of a 130 nucleotide insert between the two
      maizerbcL gene mRNA start sites. The DNA sequence adjacent to the start site for
      the large mRNA transcript is shown to have greater than 90% homology to the DNA
      sequences adjacent to the mRNA start sites for the spinach and tobaccorbcL gene.
      Discounting the presence of the insert in the maizerbcL gene, the nucleotides
      upstream from the coding sequence in the maize, spinach and tobaccorbcL genes,
      all share approximately the same amount of homology to each other. This homology,
      along with other evidence, suggests that the large mRNA species are the primary
      transcripts and that the smaller RNA species are the result of post
      transcriptional processing. The finding that spinach also contains two different
      mRNA transcripts for therbcL gene is consistent with this model. 

PMID- 24310755
TI  - A family of wheat embryo U2 snRNAs.
AB  - Evidence is presented for the existence of small nuclear RNAs in a higher plant
      species. Based on subcellular fractionation experiments, wheat embryos contain at
      least four putative snRNAs, one of which co-migrates on SDS-polyacrylamide gels
      with a relatively abundant cytoplasmic RNA, W1. We purified W1 from ribosome-free
      high speed supernatant fractions for characterization studies. Electrophoresis
      under partially denaturing conditions resolves this RNA into several components
      which bear m3 (2, 2, 7) G-5' caps and strongly resemble vertebrate U2 snRNA on
      the basis of modified nucleotide content. Preliminary sequence analyses indicate
      that wheat embryos contain at least three U2-like RNAs which possess slightly
      different sequences near their 3' ends. 

PMID- 24310756
TI  - Prevalence and clinical correlates of sleep disordered breathing in myotonic
      dystrophy types 1 and 2.
AB  - PURPOSE: Myotonic dystrophy types 1 (DM1) and 2 (DM2) are the most common
      muscular dystrophies in adulthood. A high prevalence of excessive daytime
      sleepiness (EDS) and sleep disordered breathing was documented in DM1; however,
      there are limited data available regarding DM2. Goals of the study were: (1) to
      evaluate the prevalence of sleep apnea in a large cohort of patients (71 DM1 and
      14 DM2) and (2) to analyze correlations among such disorders and clinical
      features of myotonic dystrophies. METHODS: All patients underwent clinical
      examination, subjective sleep evaluation, and home based cardiorespiratory
      monitoring, and most of them performed pulmonary function tests and oropharyngeal
      oesophageal scintigraphy (OPES). RESULTS: Almost 45% of patients reported poor
      sleep quality; only 20% of them referred EDS. Sleep studies documented sleep
      apnea, mostly obstructive, in 69% DM1 patients and 43% DM2 patients; overall, 28%
      of cases needed non-invasive ventilation. Neither age, gender, illness duration,
      body mass index, muscle involvement, OPES respiratory function indexes, nor
      n(CTG) in leukocytes were predictive of sleep apnea in DM1 patients. Conversely,
      in DM1 the central apnea-hypopnea index is correlated with the oral transit time
      estimated by OPES, whereas in DM2 apnea indexes are correlated with pulmonary
      function parameters. CONCLUSIONS: Sleep apnea is highly prevalent in both forms
      of myotonic dystrophies. In DM1, no clinical parameters appear to be predictive,
      while age appears to influence the severity of the obstructive variant; in DM2,
      the severity of sleep apnea is correlated with the degree of respiratory muscle
      involvement. Considering the harmful consequences of sleep apnea on
      cardiorespiratory function, our findings suggest including PSG in the follow-up
      of myotonic dystrophies.

PMID- 24310757
TI  - Diagnostic value of the ISAC((r)) allergy chip in detecting latex sensitizations.
AB  - PURPOSE: Latex allergy can be diagnosed by different test methods such as IgE
      quantification, Western blot, cellular antigen stimulation test (CAST), and in
      vivo methods [e.g. skin prick test (SPT)]. Phadia provides two modern methods
      using recombinant latex allergens: ImmunoCAP((r)) and the Immuno Solid-phase
      Allergen Chip (ISAC((r))), which enables simultaneous determination of specific
      IgE against five latex allergens. We compared the diagnostic sensitivity of the
      ISAC((r)) test kit and the conventional Hev b 5-spiked ImmunoCAP((r)) latex
      extract. METHODS: Forty sera were sampled from subjects with suspected natural
      rubber latex (NRL) allergy. These patients had positive SPT to NRL extract,
      positive NRL Western blots, and positive results in the CAST. All sera were
      analysed using the ISAC((r)) and recombinant NRL ImmunoCAP((r)) allergens and
      compared to the results of 20 negative control sera. RESULTS: Only 22 of the 40
      subjects (55 %) showed positivity to at least one latex allergen on the ISAC((r))
      (sensitivity ISAC((r)) 55 %). The sensitivity of the ImmunoCAP((r)) latex extract
      was 70 %. The most frequently detected sensitization was against Hev b 6.01 (n =
      12). When the serum samples were tested with all recombinant ImmunoCAP((r))
      allergens, three additional sensitizations against latex could be detected
      compared to the ISAC((r)). CONCLUSIONS: Microarrays do offer many potential
      benefits such as elegant simultaneous determination of sensitizations against
      different NRL allergens with minimal amounts of serum. However, a negative NRL
      test result should be regarded with caution and at least be confirmed by other in
      vitro methods.

PMID- 24310758
TI  - Percutaneous endovascular abdominal aortic aneurysm repair within the infrarenal
      region. Preliminary report.
AB  - The aim of the study was to thoroughly evaluate the closure device ProStar XL in
      terms of its efficiency and safety in the percutaneous endovascular treatment of
      abdominal aortic aneurysms in the infrarenal section of the body. Additionally,
      it was crucial to assess if there were any occurrences of regional complications
      at any step of the procedure. It was also important to stipulate the estimated
      hospitalization period as well as the overall cost of the PEVAR treatment with
      the use of ProStar XL. MATERIAL AND METHODS: The analysis included 21 cases with
      PEVAR performed in the infrarenal region. The final success was achieved in 98.2%
      of the cases. One PEVAR case (that constituted 0.2% of this group) was
      unsuccessful because of the bleeding while the placement of the sutures with the
      use of ProStar XL was being performed. RESULTS: This resulted in the emergency
      treatment of the CFA with the continuous stitch (Prolene 5-0). During the
      postoperative period the above described patient was given 2 units of the Packed
      Red Blood Cells (PRBC). However, this complication (unexpected bleeding) did not
      influence the length of the hospitalization period in any significant way.
      CONCLUSIONS: Percutaneous vascular closure device ProStar XL used in the
      treatment of the common femoral artery (CFA) constitutes a necessary and safe
      supplement for Endovascular Aortic Aneurysm Repair (EVAR). The implementation of
      ProStar XL closure device proves to significantly shorten the hospitalization
      period after the EVAR treatment. Additionally, the safety of the entire procedure
      is exponentially linked to the experience of the operating surgeon.

PMID- 24310759
TI  - Laparoscopic abdominoperineal resection of the rectum - how is it done; initial
      results.
AB  - The abdominoperineal resection of the rectum is a classical operation performed
      in case of patients diagnosed with rectal cancer. The development of laparoscopic
      techniques in recent years, introduced yet another method of treatment,
      considering patients with rectal cancer- laparoscopic abdominoperineal resection
      of the rectum. The aim of the study was to present initial treatment results
      considering the above-mentioned patients. MATERIAL AND METHODS: The study group
      comprised 25 patients (16 male and 9 female) diagnosed with low-rectal cancer,
      subjected to surgery by means of the above-mentioned method. Mean patient age
      amounted to 66 years. Three (12%) patients required conversion to classical
      surgery (laparotomy), while one patient required reoperation, due to presacral
      vascular bleeding. Complications were observed in 10 (40%) patients. Average
      hospitalization was 7 days. In case of all patients the radial margin was
      negative, and mean number of removed lymph nodes amounted to 9.6. Mortality was
      not observed during the perioperative period. Due to the initial character of the
      study analysis (mean observation period in case of 68% of patients was shorter
      than 2 years), oncological results were not subject to evaluation. CONCLUSIONS:
      Laparoscopic abdominoperineal resections are considered as technically difficult
      operations, requiring significant experience of the operating team. However, they
      enable the patient to take advantage of the many assets of minimally invasive
      surgery, with comparable rates of postoperative complications.

PMID- 24310760
TI  - Radiological investigation of relationship between lunate type and ulnar
      variance.
AB  - Some variances and anatomical proportions of the wrist may contribute to
      development of avascular necrosis of the lunate. Kienbock's disease is more often
      encountered in young males, who suffer, among others, from type II of the lunate
      (with two joint surfaces for the capitate and hamate) and/or negative variance of
      ulna in relation to radius. The aim of the study was to investigate whether there
      exists interdependence between the simultaneous occurrence of individual types of
      the lunate with one of the variances of ulna in both genders. MATERIAL AND
      METHODS: A retrospective analysis of 394 (n=394) radiological tests of the wrist
      in 174 (44%) women and 220 (56%) males aged 18-83 years (average age 39 years).
      From the entire pool, 265 X-rays were educed in 104 females and 161 males, and no
      fractures or wrist instability features were could be observed. The X-rays were
      obtained from computer lab and archive data base at St Hedwig Hospital in
      Trzebnica from the beginning of January 2011 to the end of December 2012.
      RESULTS: 196 cases (74%) were found with type I of the lunate and 69 cases (26%)
      with type II. Ulnar variance amounted to from +4.7 mm to -4.2 mm (mean value +0.9
      mm). Positive ulnar variance was stated in 44 patients (16.6%), negative in 63
      (23.7%) and neutral accounted for the biggest group of other 158 (59.7%)
      patients. CONCLUSIONS: Neutral variance of ulna is the one that occurs most often
      in the Polish population. There is no correlation between gender and ulnar
      variance. There is also lack of direct connection between occurrence of
      individual lunate types and ulnar variance.

PMID- 24310761
TI  - Short and long-term outcomes after primary liver transplantation in elderly
      patients.
AB  - The number of elderly patients undergoing liver transplantation (LT) is
      increasing worldwide. The aim of the study was to evaluate the impact of
      recipient age exceeding 60 years on early and long-term outcomes after LT.
      MATERIAL AND METHODS: This study comprised data of 786 patients after primary LT
      performed at a single center between January 2005 and October 2012. Patients over
      and under 60 years of age were compared with respect to baseline characteristics
      and outcomes: postoperative mortality (90-day) and 5-year patient (PS) and graft
      (GS) survival. Associations between recipient age exceeding 60 years and LT
      results were assessed in multiple Cox regression models. RESULTS: Recipients
      older than 60 years (n=107; 13.6%) were characterized by more frequent hepatitis
      C virus infections (p<0.001), malignancies (p<0.001), and cardiovascular
      comorbidities (p<0.001); less frequent primary sclerosing cholangitis (p=0.002)
      and Roux-en-Y hepaticojejunostomy (p<0.001); lower Model for End-stage Liver
      Disease (MELD; p=0.043); and increased donor age (p=0.012). Fiveyear PS of older
      and younger recipients was 72.7% and 80.6% (p=0.538), while the corresponding
      rates of GS were 70.3% and 77.5% (p=0.548), respectively. Recipient age exceeding
      60 years was not significantly associated with postoperative mortality (p=0.215),
      PS (p=0.525) and GS (p=0.572) in multivariate analyses. The list of independent
      predictors comprised MELD (p<0.001) for postoperative mortality; malignancies
      (p=0.003) and MELD (p<0.001) for PS; and malignancies (p=0.003), MELD (p<0.001)
      and donor age (p=0.017) for GS. CONCLUSIONS: Despite major differences between
      elderly and young patients, chronological age exceeding 60 years alone should not
      be considered as a contraindication for LT.

PMID- 24310762
TI  - Laparoscopic distal pancreatectomy - new standard in the pancreatic surgery.
AB  - The improvement of laparoscopic techniques that we witnessed over the last
      decade, also applied to pancreatic surgery. Both worldwide and in Poland,
      increasingly more patients with lesions located within the body and tail of the
      pancreas are treated using laparoscopic distal pancreatectomy. The aim of the
      study was to compare the outcomes of laparoscopic and open distal pancreatectomy.
      MATERIAL AND METHOD: Between January 2009 and March 2013, 107 patients underwent
      distal pancreatectomy at a single institution: 39 using laparoscopic technique
      and 68 using open technique. This was a retrospective study. RESULTS: There were
      no significance differences with regard to duration of the surgical procedure,
      duration of hospitalization and complication rate between both groups.
      Statistically significant difference was found for the incidence of spleen
      preservation in patients undergoing laparoscopy, due to better visualization of
      the structures. In the group of patients with pancreatic cancer there was no
      significance difference in the incidence of malignancy found in the surgical
      margin. Our results are similar to that presented in the literature. CONCLUSIONS:
      Laparoscopic distal pancreatectomy is a safe method, with a higher rate of spleen
      preservation among the patients with the lesion located in the body and tail of
      the pancreas.

PMID- 24310763
TI  - Comparison of outcome between older and younger patients following surgery for
      primary hyperparathyroidism.
AB  - The aim of the study was to compare preoperative findings, serum levels of
      calcium and parathormone (PTH) and outcome of patients undergoing surgery for
      primary hyperparathyroidism (pHPT) aged over 70 years with younger patients.
      MATERIAL AND METHODS: Between January 1, 1996 and September 30, 2011 186 patients
      underwent surgery for pHPT. Patient data were collected from chart reviews and an
      electronically stored database. Groups were defined as patients aged 70 years or
      older and patients younger than 70 years. Outcome comparison included operation
      time, tumor size, pre- and postoperative serum levels of calcium and PTH and
      length of stay in hospital. Complications were defined as clinical and laboratory
      signs of hypocalcemia, persistent elevated serum calcium, temporary or persistent
      recurrent laryngeal nerve paralysis, bleeding with need for reoperation, surgical
      site infection or need of tracheotomy. RESULTS: Parathyroidectomy alone was
      performed in 39.2% of patients. In 60.8% partial or total thyroidectomy was
      conducted simultaneously. More older patients had history of stroke and/or
      suffered from diabetes. Preoperative serum calcium and PTH did not differ between
      groups, but older patients displayed higher postoperative serum calcium (p=0.01).
      No significant differences between the two groups were observed regarding
      duration of surgery, surgical success rates, postoperative complications and
      hospitalization time. CONCLUSIONS: Even though older patients had more risk
      factors, our data suggest that there was no difference in surgical management and
      outcome. Decision for surgical management of pHPT should be done regardless of
      age.

PMID- 24310764
TI  - Volvulus of transverse colon as a rare cause of obstruction - a case report and
      literature review.
AB  - Volvulus of transverse colon is a rare cause of large bowel obstruction.
      Diagnosis can be challenging and the effective management remains controversial.
      We report a case of volvulus of the transverse colon in a 76-year-old woman. The
      literature regarding diagnosis and treatment of such pathology was also reviewed.

PMID- 24310765
TI  - Aspergillosis - diagnostic and therapeutic difficulties in critically ill
      surgical patients.
AB  - Improving the effectiveness of the treatment of critically ill and their longer
      survival has increased the existence of later complications rarely seen before.
      Among the hospital-acquired infections such complications include infection of
      mold fungi. The paper presents difficulties in diagnosing and therapy of
      Aspergillus mold infections illustrating them with the description of cases when
      Aspergillus infection occurred during the treatment of critically ill, leading
      with treatment delay to high mortality.

PMID- 24310766
TI  - The potential of bacteriophages in the treatment of burn wounds.

PMID- 24310767
TI  - Infections in notes.

PMID- 24310768
TI  - Repetitive administration of acetylcholine receptor agonist rescues brain
      inflammation and brain damage after hypoxia-ischemia in newborn rat.
AB  - OBJECTIVE: We examined the effect of repetitive administration of acetylcholine
      receptor agonist (carbachol) on brain damage and microglial accumulation in three
      brain regions after hypoxia-ischemia (HI) in newborn rat. STUDY DESIGN: Seven-day
      old Wistar rats were divided into two groups, one receiving a 0.1 mg/kg dose of
      carbachol on days 7, 8 and 9 to examine the attenuating effect on brain damage
      with decreasing accumulation of microglia, and the other group receiving saline
      as a control. Rats were subjected to left carotid artery ligation followed by
      hypoxia. We evaluated brain damage and the number of microglias in three regions
      on days 10 and 14. RESULTS: Brain tissue was better preserved in the carbachol
      group on days 10 and 14. Microglial accumulation in the cortex was strong and
      persisted from day 10s to 14 in the control. Conversely, the accumulation of
      microglias was attenuated in the hippocampus and white matter on day 14.
      Carbachol significantly reduced the number of microglias in the hippocampus and
      white matter on day 10 and in the cortex on days 10 and 14. CONCLUSION: The main
      area of late inflammation was the cortex. Repetitive administration of carbachol
      reduces early and late inflammation after HI in the developing brain.

PMID- 24310769
TI  - Hysteroscopic and laparoscopic management of uterine defects on previous cesarean
      delivery scars.
AB  - OBJECTIVE: To examine the treatment of previous cesarean delivery scar defect
      after cesarean delivery and the feasibility of laparoscopic uterine repair or
      hysteroscopic scar excision. STUDY DESIGN: A retrospective clinical study that
      took place from June 2009 to March 2013 and included 41 women who had previously
      had cesarean deliveries. RESULTS: Seventeen women underwent a laparoscopic
      approach for the repair of scar diverticula, and 24 women underwent a
      hysteroscopic resection of fibrotic tissue overhanging underneath the
      diverticula. Most women remained free of symptoms over a 3- to 16-month follow-up
      and 6 women became pregnant without pregnancy complications. CONCLUSION: Women
      with a history of cesarean delivery combined with irregular perimenstrual
      bleeding should undergo combined hysteroscopy and ultrasound examination to
      detect latent scar defects. In diagnosed cases, in those who desired future
      pregnancies and had a residual myometrial thickness of <3.5 mm or a defect that
      accounted for >=50% of the anterior uterine wall, laparoscopic surgical repair
      was performed with good postoperative anatomic outcomes. Women with residual
      myometrial thickness of >=3.5 mm or a defect that accounted for <50% of the
      anterior uterine wall were treated with hysteroscopic surgery and had a relief of
      symptoms.

PMID- 24310770
TI  - The factors associated with the failure of transcatheter pelvic arterial
      embolization for intractable postpartum hemorrhage.
AB  - OBJECTIVE: The transcatheter pelvic arterial embolization (TAE) is effective for
      postpartum hemorrhage (PPH). There has been a little information about the
      factors for ineffectiveness of TAE. The aim of this study was to determine
      factors associated with TAE failure for PPH. STUDY DESIGN: Fifty-five women who
      underwent TAE for intractable PPH were included. Clinical factors involving age,
      history of pregnancy, gestational weeks of delivery, mode of delivery, causes of
      PPH, complete blood count, blood loss volume, transfusion amount, shock index and
      disseminated intravascular coagulation (DIC) score were compared between TAE
      success group (n=48) and TAE failure group (n=7). RESULTS: The uni- and multi
      variate analyses revealed that advanced maternal age (OR 1.46, 95% CI 1.12-2.18)
      and retained placenta as a cause of PPH (15.48, 2.04-198.12) were found to be
      significant factors for TAE failure. CONCLUSION: The advanced age and retained
      placenta were independent factors associated with TAE failure for intractable
      PPH.

PMID- 24310771
TI  - Quantitative detection of target cells using unghosted cells (UGCs) of DxH 800
      (Beckman Coulter).
AB  - BACKGROUND: In the Retic channel of DxH 800 (Beckman Coulter), the red blood
      cells (RBCs) resistant to hemoglobin clearing are counted as unghosted cells
      (UGCs). The aim of this study was to evaluate that the UGC is a surrogate marker
      for both the detection and counting of target cells. METHODS: In total, 1181
      samples including 22 from iron deficiency anemia (IDA) patients, 95 from
      jaundice, 2 from sickle cell anemia, 3 from thalassemia, 1 cord blood, and 269
      from normal controls were analyzed. Slides were prepared from all samples except
      normal controls and target cells were counted for correlation analysis of target
      cell counts to UGCs. RESULTS: The normal control samples showed 0.01% (0%-0.01%)
      UGCs, and the reference range was set at <=0.02%. The IDA samples showed 0.015%
      (0.01%-0.03%) UGC count and 0.05% (0%-0.2%) target cell count. The jaundice
      samples showed 0.98% (0.1%-5.36%) UGC count, and 1.4% (0.1%-7.0%) target cell
      count. The two sickle cell anemia samples showed 0.41% and 3.74% UGC counts and
      0.4% and 11.5% target cell counts. A cord blood sample showed 0.01% UGCs and 0%
      target cells. The three thalassemia samples showed 0.01%, 1.99%, and 7.82% UGC
      counts and 0%, 1.4%, and 15.5% target cell counts. The samples showing
      poikilocytosis other than target cells showed normal UGC count (<=0.02%). The
      positive predictive value of UGCs was 58.2% (124/213) and the negative predictive
      value was 96.8% (674/696). The UGC counts were well correlated to the manual
      target cell counts (r=0.944, p=0.000). CONCLUSIONS: This study demonstrates for
      the first time in the literature that a hematological parameter obtained
      automatically every time a reticulocyte counting is performed can be used to both
      screen for the presence of target cells and reliably quantify them.

PMID- 24310772
TI  - Evaluation of different sized blood sampling tubes for thromboelastometry,
      platelet function, and platelet count.
AB  - BACKGROUND: To minimise the volume of blood used for diagnostic procedures,
      especially in children, we investigated whether the size of sample tubes affected
      whole blood coagulation analyses. METHODS: We included 20 healthy individuals for
      rotational thromboelastometry (RoTEM(r)) analyses and compared three blood
      sampling tubes of different size: 1.8, 2.7, and 3.6 mL. All tubes were made of
      plastic and contained 3.2% sodium-citrate as anticoagulant. Platelet aggregation
      was investigated in 12 healthy individuals employing the Multiplate(r) Analyser
      comparing tubes of 3.6 mL and 1.8 mL. Platelet count was determined for each of
      the sampling tubes after 10, 60, and 120 min. RESULTS: No significant differences
      were found in any of the RoTEM(r) measurements between the three sizes of tubes
      (p=0.07-0.53). Platelet aggregation was significantly lower when using smaller
      tubes (p=0.0004). The platelet count remained stable using a 3.6 mL tube during
      the entire observation period of 120 min (p=0.74), but decreased significantly
      after 60 min when using tubes smaller than 3.6 mL (p<0.0001). CONCLUSIONS:
      RoTEM(r) analyses were not affected by the size of blood sampling tubes.
      Therefore, 1.8 mL tubes should be preferred for RoTEM(r) analyses in order to
      minimise the volume of blood drawn. With regard to platelet aggregation analysed
      by impedance aggregometry tubes of different size cannot be used interchangeably.
      If platelet count is determined later than 10 min after blood sampling using
      tubes containing citrate as anticoagulant, a 3.6 mL tube should be preferred to
      avoid false low values.

PMID- 24310774
TI  - The adolescent as theorist: An interpretive view.
AB  - This article advances a way of conceptualizing the adolescent as "theorist"
      derived from interpretive sociology. This formulation of the adolescent as
      theorist is contrasted to that available within Piagetian theory. It emphasizes
      the practical and the occasioned nature of theoretical activity and shows it in
      everyday settings. Interview conversation between an adolescent and an adult is
      used as empirical illustration. This formulation of the adolescent as theorist is
      offered as a means of entry to the scientific constitution of the adolescent as a
      practitioner of world building who uses the same available resources and does the
      same sense-making work as any competent member in a culture. 

PMID- 24310773
TI  - Relationship between prostate-specific antigen kinetics and detection rate of
      radiolabelled choline PET/CT in restaging prostate cancer patients: a meta
      analysis.
AB  - BACKGROUND: The aim of the article was to systematically review published data
      about the relationship between prostate-specific antigen (PSA) kinetics,
      including PSA doubling time (PSAdt) and PSA velocity (PSAvel), and detection rate
      (DR) of positron emission tomography/computed tomography (PET/CT) using
      radiolabelled choline in restaging prostate cancer (PCa). METHODS: A
      comprehensive literature search of studies published through July 2013 regarding
      the relationship between PSA kinetics and DR of radiolabelled choline PET/CT was
      carried out. Furthermore, a meta-analysis was performed in order to establish the
      DR of radiolabelled choline PET/CT using different cut-off values of PSAdt (<= or
      >6 months) and PSAvel [>1 or <=1 ng/(mL year) and >2 or <=2 ng/(mL year)].
      Moreover, a pooled analysis to establish whether PSAdt and PSAvel (using the
      abovementioned cut-off values) may predict positive PET/CT results was carried
      out. RESULTS: Fourteen articles were selected. The pooled DR of radiolabelled
      choline PET/CT in restaging PCa was 58% [95% confidence interval (CI) 55-60].
      Most articles reported a relationship between PSA kinetics and DR of PET/CT.
      Pooled DR of radiolabelled choline PET/CT increased to 65% (95% CI 58-71) when
      PSAdt was <=6 months and to 71% (95% CI 66-76) and 77% (95% CI 71-82) when PSAvel
      was >1 or >2 ng/(mL year), respectively. PSAdt <=6 months and PSAvel >1 or >2
      ng/(mL year) proved to be relevant factors in predicting the positive result of
      radiolabelled choline PET/CT. CONCLUSIONS: Due to the strong relationship between
      PSA kinetics and DR of radiolabelled choline PET/CT, beyond PSA values, PSAdt and
      PSAvel should be taken into account in the selection of PCa patients who should
      undergo radiolabelled choline PET/CT for restaging.

PMID- 24310775
TI  - Jumping off the work experience bandwagon.
AB  - This paper summarizes and reviews the literature on the impact of work experience
      during the adolescent years. Research in three areas is reviewed: work experience
      through career education programs; work experience through youth employment and
      training programs; and work experience through part-time employment. In general,
      the findings in all three areas indicate that the benefits of working to
      education, socialization, and subsequent employment have been greatly
      overestimated. 

PMID- 24310776
TI  - Moral development and discipline encounter in delinquent and nondelinquent
      adolescents.
AB  - The present study tested whether Hoffman's conceptualization of the relationship
      between disciplinary techniques and moral development can account for findings
      that delinquents score lower than nondelinquents on various measures of moral
      development. Twenty-six delinquent adolescents, 20 middle class nondelinquents,
      and 20 lower class non-delinquents were assessed on moral development using the
      following measures: resistance to temptation, moral stage, feelings after
      offense, judgment about the severity of punishment, and confession. The use of
      induction by parents was examined with a Q-sort administered to adolescents and
      their parents. On most measures of moral development delinquents performed lower
      than nondelinquents. Less induction was found to be used with delinquents than
      with nondelinquents. Induction was positively related to most moral measures. It
      was concluded that disciplinary methods may account for differential moral
      development of delinquent versus nondelinquent adolescents. 

PMID- 24310777
TI  - Adjustment and sex-role orientation in adolescence.
AB  - The purpose of the present study was to reexamine the relationship between sex
      role orientation and self-esteem in adolescence. One hundred and six senior high
      school students completed the Rosenberg self-esteem measure (Rosenberg, 1965) and
      two measures of sex-role orientation, the Bem Sex Role Inventory, Short Form
      (BSRI; Bem, 1981), and the Personal Attributes Questionnaire Short Form (PAQ;
      Spence et al., 1975). The relationship between sex-role orientation and self
      esteem was found to vary depending on the sex-role measure employed. Results of
      the BSRI revealed that androgynous individuals had higher levels of self-esteem
      than masculine, feminine, and undifferentiated adolescents. PAQ results indicated
      that androgynous individuals had higher levels of self-esteem than feminine and
      undifferentiated individuals. When the independent contributions of masculinity
      and femininity were assessed, both BSRI and PAQ masculinity and femininity
      significantly predicted self-esteem. Analyses also revealed that the effects of
      sex-role orientation on self-esteem varied by sex across both the BSRI and PAQ.
      Implications of the present findings for previous work on sex-role development in
      adolescence are discussed. 

PMID- 24310778
TI  - Aggression, deviance, and personality adaptation as antecedents and consequences
      of alienation and involvement in high school.
AB  - Alienation from, or involvement in, the social and educational systems of the
      high school are investigated in an effort to determine the extent that school
      experiences may influence aggressive and deviant behavior in school and
      personality styles or orientations. Drawing upon longitudinal data collected from
      250 boys followed from grades 8 through 12, potential antecedent-consequence
      relationships between dimensions of alienation and involvement and these two
      basic types of student outcomes are examined by cross-lagged panel analyses.
      Differences between cross-lagged panel correlations provide evidence that student
      reactions and attachments to school manifest relationships with aggression,
      deviance, and personality, serving as both antecedents and consequences of these
      student adaptations. The major findings provide evidence that (1) boys who more
      frequently break school rules and engage in aggressive or deviant behavior may
      often come to have more negative attitudes toward school staff and less
      involvement in school; and (2) student involvement and participation in school
      life can influence certain aspects of adolescent personality. Possible evidence
      of reciprocal causation is presented and discussed, as are additional theoretical
      and methodological implications of the data. 

PMID- 24310779
TI  - Coffee and green tea consumption is associated with upper aerodigestive tract
      cancer in Japan.
AB  - The impact of coffee and green tea consumption on upper aerodigestive tract
      (UADT) cancer risk has not been established. Evaluation of the possible
      anticarcinogenic properties of their ingredients is confounded by the potential
      increase in risk owing to the high temperatures at which these beverages are
      generally consumed. We conducted a case-control study to evaluate the association
      between coffee and tea consumption and the risk of UADT cancer. The study
      enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who
      visited Aichi Cancer Center between 2001 and 2005. Information on coffee and
      green tea consumption and other lifestyle factors was collected via a self
      administered questionnaire. Consumption of three or more cups of coffee per day
      had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95%
      confidence interval (CI) 0.55-0.96]. In contrast, consumption of three or more
      cups of green tea per day had a significant positive association with UADT cancer
      (OR 1.39, 95% CI 1.13-1.70). These associations were evident for head and neck
      cancer but not for esophageal cancer. The association of coffee consumption with
      head and neck cancer was observed only among never smokers and alcohol drinkers.
      Similarly, the association of green tea consumption was observed among never
      smokers and never alcohol drinkers. No change in these associations was seen on
      stratification by each confounding factors. These findings suggest that
      consumption of coffee might be associated with a decreased risk of UADT cancer,
      whereas that of green tea might be associated with an increased risk. 

PMID- 24310780
TI  - Astrocyte-specific activation of TNFR2 promotes oligodendrocyte maturation by
      secretion of leukemia inhibitory factor.
AB  - Tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2 have pleiotropic
      effects in neurodegenerative disorders. For example, while TNFR1 mediates
      neurodegenerative effects in multiple sclerosis, TNFR2 is protective and
      contributes to remyelination. The exact mode of TNFR2 action, however, is poorly
      understood. Here, we show that TNFR2-mediated activation of the PI3K-PKB/Akt
      pathway in primary astrocytes increased the expression of neuroprotective genes,
      including that encoding the neurotrophic cytokine leukemia inhibitory factor
      (LIF). To investigate whether intercellular signaling between TNFR2-stimulated
      astrocytes and oligodendrocytes plays a role in oligodendrocyte maturation, we
      established an astrocyte-oligodendrocyte coculture model, composed of primary
      astrocytes from huTNFR2-transgenic (tgE1335) mice and oligodendrocyte progenitor
      cells (OPCs) from wild-type mice, capable of differentiating into mature
      myelinating oligodendrocytes. In this model, selective stimulation of human TNFR2
      on astrocytes, promoted differentiation of cocultured OPCs to myelin basic
      protein-positive mature oligodendrocytes. Addition of LIF neutralizing antibodies
      inhibited oligodendrocyte differentiation, indicating a crucial role of TNFR2
      induced astrocyte derived LIF for oligodendrocyte maturation.

PMID- 24310781
TI  - Vitamin D levels in patients with chronic hepatitis B.

PMID- 24310783
TI  - Meditation and health.

PMID- 24310782
TI  - Size of the social network versus quality of social support: which is more
      protective against PTSD?
AB  - PURPOSE: Supportive social networks are important to the post-traumatic response
      process. However, the effects of social network structure may be distinct from
      the perceived function of those networks. The present study examined the relative
      importance of role diversity and perceived strength of social support in
      mitigating post-traumatic stress disorder (PTSD). METHODS: Data were drawn from
      respondents who report lifetime potentially traumatic events in the National
      Epidemiologic Survey on Alcohol and Related Conditions (N = 31,650). The Social
      Network Index (SNI) was used to measure the diversity of social connections. The
      Interpersonal Support Evaluation List (ISEL-12) was used to measure the perceived
      availability of social support within the network. Odds of current PTSD were
      compared among individuals representing four dichotomous types of social support:
      high diversity/high perceived strength, high diversity/low perceived strength,
      low diversity/high perceived strength, and low diversity/low perceived strength
      to examine which type of support is more protective against PTSD. RESULTS:
      Unadjusted odds of PTSD were 1.59 (95 % CI 1.39-1.82) for those with low versus
      high perceived support strength, and 1.10 (0.94-1.28) among those with non
      diverse versus diverse social networks. Compared to the reference group (high
      diversity/high perceived strength), the adjusted odds of current PTSD were higher
      for two groups: low diversity/low perceived strength (OR = 1.62; 1.33-1.99), and
      low diversity/high perceived strength (OR = 1.57; 1.3-1.91). The high
      diversity/low perceived strength group had no greater odds of PTSD (OR = 1.02;
      0.81-1.28). CONCLUSION: The diversity of a social network is potentially more
      protective against PTSD than the perception of strong social support. This
      suggests that programs, which engage individuals in social groups and activities
      may effectively attenuate the risk of PTSD. A better understanding of how these
      networks operate with respect to PTSD prevention and mitigation holds promise for
      improving psychiatric health.

PMID- 24310784
TI  - Religion and medicine: A theoretical overview.
AB  - Recent scholarly studies in history, sociology, anthropology, religion, and
      psychosomatic medicine, coupled with clinical experience in the care of patients,
      call for a reassessment of the interrelationships between religion and medicine.
      Six major areas of interaction between these forms of human experience are
      identified and outlined. Investigations into these interlinkages not only offer
      challenging new opportunities for discovery but also hold promise for the
      development of new, more effective forms of medical care and healing. This new
      understanding of the interconnections between medicine and religion has many
      implications both for health care practitioners and for professionals with
      specialized training in religious studies. 

PMID- 24310785
TI  - Ending human relationships: Problems and potentials.
AB  - The endings of human relationships, the processes of separation and termination,
      are discussed by the author, a psychoanalytically oriented psychiatrist, from the
      perspective of individual and group psychotherapy. Separations are viewed as
      psychologically traumatic, activating psychic states analogous to those seen in
      early childhood. The loss reactivates the toddler experience of giving up the
      mother as an encompassing need-satisfying object. A process of unresolved
      mourning ensues. The relationship of this entire experience to early states of
      self-identity formation explains its traumatic nature, yet provides new
      opportunities for continued consolidation of the sense of self. This, in turn,
      enhances one's potential for mutuality in new relationships. 

PMID- 24310786
TI  - Individual needs and charismatic promises.
AB  - Using psychoanalytic theory, the author explains how a woman came to devote
      herself to a man's group that conceived of itself as the New Kingdom of God. He
      refers to notes from counseling sessions with the woman, Jane, and to excerpts
      from the book,T, which is an autobiography of the group's leader, Thomas. The
      author compares their ego profiles as measured on ego assessment scales and
      argues that this allows us to see how Thomas gained his charismatic status. 

PMID- 24310787
TI  - Religion, psychology, and mental health: The problems of partnership.
AB  - While a current and increasingly popular trend is toward partnerships between
      religion and psychology in the area of mental health, and especially toward the
      use of psychological ideas and techniques by pastoral counselors, modern
      psychology and traditional religion are divided in significant ways over several
      normative issues. Too often these issues are minimized or overlooked. But unless
      these issues-which carry significant sociocultural implications as well as
      implications for our definitions of individual well-being-are acknowledged and
      subjected to critical considerations, partnerships between religion and
      psychology must be far more cautiously constructed and must be subjected to far
      more systematic thinking about the differences which separate the two. 

PMID- 24310788
TI  - A potential peril of pastoral care: Malpractice.
AB  - The pastoral counselor may be a full-time counselor trained in pastoral care or a
      clergyman with a congregation, who from time to time serves his flock as a
      counselor, ministering to the personal needs of his congregation in a manner
      designated "pastoral care" or perhaps, more appropriately, "pastoral
      psychotherapy." Once a therapeutic relationship is established, a congregant
      acquires certain rights and the clergyman, duties. If these duties are breached
      due to the negligence of the pastoral counselor and this causes the congregant to
      be damaged in any way, the pastoral counselor may be liable and may be called
      upon to respond in damages. The cause of action is called malpractice. This paper
      isolates areas of actual and potential malpractice. 

PMID- 24310789
TI  - The missionary syndrome.
AB  - Early sexual explorations of children that are of a traumatic nature are often
      labeled by the child as "bad" or "wrong" and subsequently repressed. The guilt
      that results from the labeling may be intensified at a later date by some other
      similar incident, and at this time the person may make a binding commitment or
      promise to God to serve Him in some dutiful way. If, at a later date, these plans
      to serve God cannot be realized, depression, phobias, or conversion
      symptomatology may occur, which we have referred to as the Missionary Syndrome. 

PMID- 24310790
TI  - Brainwashing and the persecution of "cults".
AB  - While the presence of authoritarian "cults" in our midst raises a number of
      social control and "law and order" issues, current controversies over cults
      contain substantial elements of mystification. "Brainwashing" is an inherently
      subjective metaphor that is used as a rationale for persecuting unpopular
      movements and defining religious converts as nonautonomous zombies who can be
      coerced for therapeutic purposes. While "coercive persuasion" models do have some
      heuristic value for the analysis of indoctrination in some authoritarian groups,
      assumptions regarding the alleged destruction of the "free will" of converts and
      the status of authoritarian religiosity as a medical pathology are not warranted.

PMID- 24310791
TI  - Thoracoscopic color and fluorescence imaging system for sentinel lymph node
      mapping in porcine lung using indocyanine green-neomannosyl human serum albumin:
      intraoperative image-guided sentinel nodes navigation.
AB  - PURPOSE: This study was performed to validate a newly developed sentinel lymph
      node (SLN) targeting tracer, indocyanine green-neomannosyl human serum albumin
      (ICG:MSA), and a thoracoscopic version of the intraoperative color and
      fluorescence imaging system (ICFIS) for lung cancer SLN mapping. METHODS: ICG
      alone or ICG:MSA (5 MUg/kg) was injected into the rat thigh, and the results were
      compared. The fluorescence signal-to-background ratios of SLNs were recorded and
      evaluated over a 2-h period by using ICFIS. Additionally, a SLN biopsy was
      performed via video-assisted thoracoscopic surgery with the use of ICG:MSA in
      porcine lung by using thoracoscopic ICFIS. RESULTS: The newly developed ICG:MSA
      showed a significantly improved signal-to-background ratio compared with ICG
      alone throughout the trials. All SLNs were identified in both rats (ten SLNs in
      ten rat thighs) and pigs (ten SLNs in ten porcine lungs) under in vivo
      conditions. All SLNs were dissected successfully by using video-assisted
      thoracoscopic surgery with the help of thoracoscopic ICFIS. DISCUSSION: ICG:MSA
      accumulates in the SLN by uptake and retention through the mannose-specific
      receptors on macrophages. Thoracoscopic ICFIS successfully assisted SLN mapping
      despite low near-infrared light transmission in the commercial thoracoscope. On
      the basis of the results of the thoracoscopic SLN mapping, we anticipate that
      ICG:MSA and thoracoscopic ICFIS can be translated to clinical trials in the near
      future.

PMID- 24310792
TI  - Immunological impact of neoadjuvant chemoradiotherapy in patients with borderline
      resectable pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Little is known about the immunological effect of neoadjuvant
      chemoradiotherapy (NACRT) in the tumor microenvironment of pancreatic ductal
      adenocarcinoma. The objective of this study was to examine the immunological
      modifications induced by NACRT in patients with pancreatic cancer. METHODS: Fifty
      two patients with pancreatic cancer who underwent surgical resection were
      enrolled in this study. NACRT was administered to 22 patients, whereas the other
      30 patients underwent surgical resection without NACRT. The resected tumor
      specimens were analyzed for the presence of tumor-infiltrating lymphocytes by
      using immunohistochemical staining for CD4, CD8, CD68, CD163, Foxp3, and major
      histocompatibility complex class I (MHC class I) antigen. RESULTS: The number of
      CD4+ and CD8+ lymphocytes was significantly higher in patients who received NACRT
      than in those who did not receive NACRT. No significant difference in MHC class I
      expression was observed between the groups. In the NACRT group, patients with a
      high accumulation of CD8+ cells experienced longer overall survival than those
      with a low number of CD8+ cells. CONCLUSIONS: NACRT may induce the accumulation
      of CD4+ and CD8+ cells in the tumor microenvironment and a high accumulation of
      CD8+ cells might be a good prognostic marker for pancreatic cancer treated with
      NACRT.

PMID- 24310793
TI  - Timing of liver surgery for colorectal liver metastases will be influenced by
      tumor behavior.

PMID- 24310794
TI  - Identification of pro- and anti-proliferative oligosaccharides of heparins.
AB  - Heparins, unfractionated heparin (UFH) and low molecular weight heparins (LMWHs),
      are heterogeneous mixtures of anticoagulant and non-anticoagulant
      oligosaccharides. In addition to their well-known anticoagulant effect, heparins
      have shown to mediate a wide range of non-anticoagulant effects, including the
      modulation of cellular growth. However, contradictory results have been reported
      with regard to their effects on cellular proliferation, with some studies
      suggesting anti-proliferative while others indicating pro-proliferative effects.
      This study investigated the proliferation of human colonic epithelial cancer
      cells in the presence of UFH and LMWHs (enoxaparin and dalteparin). In our
      experimental setting, all heparins caused a dose-dependent reduction in cellular
      growth, which correlated well with the induction of cell cycle arrest in the G1
      phase and which was not associated with significant changes in cell viability.
      The effects on cellular proliferation of 14 different oligosaccharides of
      enoxaparin obtained through ion-exchange chromatography were also assessed.
      Surprisingly, only two oligosaccharides showed distinctive anti-proliferative
      effects while the majority of oligosaccharides actually stimulated proliferation.
      Interestingly, the smallest oligosaccharide devoid of any anticoagulant activity
      showed the strongest anti-proliferative effect. Notably, heparins are currently
      standardised only according to their anticoagulant activity but not based on
      other non-anticoagulant properties. Our results indicate that slight differences
      in the composition of heparins' non-anticoagulant oligosaccharides, due to
      different origins of material and preparation methods, have the potential to
      cause diverse effects and highlight the need for additional characterisation of
      non-anticoagulant activities.

PMID- 24310795
TI  - Global Health Governance: a rising challenge.

PMID- 24310796
TI  - Use of nouns and verbs in the oral narrative of individuals with hearing
      impairment and normal hearing between 5 and 11 years of age.
AB  - CONTEXT AND OBJECTIVE: Nouns and verbs indicate actions in oral communication.
      However, hearing impairment can compromise the acquisition of oral language to
      such an extent that appropriate use of these can be challenging. The objective of
      this study was to compare the use of nouns and verbs in the oral narrative of
      hearing-impaired and hearing children. DESIGN AND SETTING: Analytical cross
      sectional study at the Department of Speech-Language and Hearing Sciences,
      Universidade Federal de Sao Paulo. METHODS: Twenty-one children with moderate to
      profound bilateral neurosensory hearing impairment and twenty-one with normal
      hearing (controls) were matched according to sex, school year and school type. A
      board showing pictures was presented to each child, to elicit a narrative and
      measure their performance in producing nouns and verbs. RESULTS: Twenty-two
      (52.4%) of the subjects were males. The mean age was 8 years (standard deviation,
      SD = 1.5). Comparing averages between the groups of boys and girls, we did not
      find any significant difference in their use of nouns, but among verbs, there was
      a significant difference regarding use of the imperative (P = 0.041): more
      frequent among boys (mean = 2.91). There was no significant difference in the use
      of nouns and verbs between deaf children and hearers, in relation to school type.
      Regarding use of the indicative, there was a nearly significant trend (P =
      0.058). CONCLUSION: Among oralized hearing-impaired children who underwent speech
      therapy, their performance regarding verbs and noun use was similar to that of
      their hearing counterparts.

PMID- 24310797
TI  - Frequency of MTHFR G1793A polymorphism in individuals with early coronary artery
      disease: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: Atherosclerotic disease is the leading cause of death in
      Brazil. It is a complex disease and its prevention involves identification and
      control of risk factors. Moderately increased plasma homocysteine concentration
      (hyperhomocysteinemia) has been considered to be a risk factor for several
      vascular diseases. Mutations in the methylenetetrahydrofolate reductase (MTHFR)
      enzyme, which is involved in homocysteine metabolism, have been investigated as
      potential vascular disease risk factors. G1793A polymorphism was described in
      2002 and there are few studies analyzing its involvement in diseases. The
      objective of this study was to investigate the prevalence of G1793A polymorphism
      in subjects with early coronary artery disease (CAD). DESIGN AND SETTING: Cross
      sectional study with control group conducted at a private cardiology clinic and a
      molecular biology laboratory (Universidade do Vale do Itajai). METHODS: We
      studied 74 early-onset CAD+ patients and 40 CAD- individuals with normal
      angiography results. DNA was extracted from blood samples. Molecular data were
      obtained via PCR/RFLP and agarose gel electrophoresis. RESULTS: The occurrence of
      G1793A heterozygotes was similar in the control (5%) and test (6.25%) groups,
      thus showing that in the population studied there was no correlation between the
      marker and occurrences of early CAD. There was also no association between the
      polymorphism and the risk factors for atherosclerosis. CONCLUSIONS: The frequency
      of the 1793A allele in the test group (3.4%) was similar to what was found in the
      control individuals (2.5%). There was no correlation between G1793A polymorphism
      and occurrences of early CAD in this population.

PMID- 24310798
TI  - Prevalence of allergen sensitization, most important allergens and factors
      associated with atopy in children.
AB  - CONTEXT AND OBJECTIVE: Knowledge of the profile of allergen sensitization among
      children is important for planning preventive measures. The objective of this
      study was to assess the prevalence and profile of sensitization to inhaled
      allergens and food among children and adolescents in an outpatient population in
      the city of Palmas. DESIGN AND SETTING: Cross-sectional study at outpatient
      clinics in Palmas, Tocantins, Brazil. METHODS: Ninety-four patients aged 1-15
      years who were attending two pediatric outpatient clinics were selected between
      September and November 2008. All of the subjects underwent clinical interviews
      and skin prick tests. RESULTS: A positive skin prick test was observed in 76.6%
      of the participants (72.3% for inhalants and 28.9% for food allergens). The most
      frequent allergens were Dermatophagoides pteronyssinus (34%), cat epithelium
      (28.7%), dog epithelium (21.3%), Dermatophagoides farinae (19.1%), Blomia
      tropicalis (18.1%), cow's milk (9.6%) and grasses (9.6%). A positive skin prick
      test correlated with a history of atopic disease (odds ratio, OR = 5.833; P =
      0.002), a family history of atopic disease (OR = 8.400; P < 0.001), maternal
      asthma (OR = 8.077; P = 0.048), pet exposure (OR = 3.600; P = 0.012) and cesarean
      delivery (OR = 3.367; P = 0.019). CONCLUSION: Dermatophagoides pteronyssinus was
      the most frequent aeroallergen and cow's milk was the most prevalent food
      allergen. There was a positive correlation between a positive skin prick test and
      several factors, such as a family history of atopic disease, maternal asthma, pet
      exposure and cesarean delivery.

PMID- 24310799
TI  - Frequency of intraoperative cardiac arrest and medium-term survival.
AB  - CONTEXT AND OBJECTIVE: Although advances in surgical and anesthetic techniques
      have reduced perioperative morbidity-mortality, the survival rate following
      cardiac arrest remains low. The aim of this study was to evaluate, over the
      course of one year, the prevalence of intraoperative cardiac arrest and the 30
      day survival rate after this event in a tertiary teaching hospital. DESIGN AND
      SETTING: Prospective cohort study in a tertiary teaching hospital. METHODS:
      Following approval by the institutional ethics committee, anesthetic procedures
      and cases of intraoperative cardiac arrest between January and December 2007 were
      evaluated. Patients undergoing cardiac surgery were excluded. The data were
      gathered prospectively using the modified Utstein model, with evaluation of
      demographic data, pre-arrest conditions, intraoperative care, care during arrest
      and postoperative outcome up to the 30th day. The data were recorded by the
      attending anesthesiologist. RESULTS: During the study period, 40,379 anesthetic
      procedures were performed, and 52 cases of intraoperative cardiac arrest occurred
      (frequency of 13:10,000). Among these, 69% presented spontaneous return of
      circulation after the initial arrest, and only 25% survived for 30 days after the
      event. The following factors were associated with shorter survival: American
      Society of Anesthesiologists physical status IV and V, emergency surgery,
      hemorrhagic events, hypovolemia as the cause of arrest and use of atropine during
      resuscitation. CONCLUSIONS: Although the frequency of cardiac arrest in the
      surgical environment has declined and resources to attend to this exist, the
      survival rate is low. Factors associated with worst prognosis are more frequent
      in critical patients.

PMID- 24310800
TI  - Association between low bone mass and calcium and caffeine intake among
      perimenopausal women in Southern Brazil: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: Osteoporosis is a skeletal abnormality characterized by
      reduction and alteration of bone microarchitecture that results in increased
      fragility and greater predisposition to fractures. Age and low bone mass are the
      main non-modifiable risk factors for osteoporotic fractures. The modifiable
      factors include sedentary lifestyle, inadequate calcium intake, excessive alcohol
      and/or caffeine consumption, smoking and low body weight. The aim here was to
      evaluate the association between low bone mass and calcium and caffeine intake
      among perimenopausal women in Southern Brazil. DESIGN AND SETTING: Cross
      sectional study conducted in Porto Alegre and Canoas, Rio Grande do Sul, Brazil.
      METHODS: Women (n = 155) of mean age 53.6 +/- 9.5 years were evaluated through a
      cross-sectional study in Southern Brazil. Food frequency questionnaires, bone
      mass evaluation using calcaneal ultrasound and anthropometric assessment were
      used. RESULTS: The prevalence of overweight was 67.7%. In the bone mass
      screening, 30.3% had low bone mass and 4.5% had osteoporosis. The median calcium
      intake was 574.94 mg/day and the caffeine intake was 108.11 mg/day. No
      association was found between bone mass and anthropometric parameters, calcium
      intake or caffeine intake. It was found that 38.4% of the women had low bone
      mass. CONCLUSIONS: No association was found between calcium and caffeine intake
      and bone mass. High prevalence of low bone mass was observed.

PMID- 24310801
TI  - Prevalence of obesity and cardiovascular risk among children and adolescents in
      the municipality of Santa Cruz do Sul, Rio Grande do Sul.
AB  - CONTEXT AND OBJECTIVE: Studies have demonstrated that metabolic complications
      from child obesity, although silent, increase the risk of development of
      cardiovascular diseases in adulthood. The present paper sought to describe the
      prevalence of overweight/obesity and analyze the possible relationship between
      obesity and other cardiovascular risk factors among children and adolescents.
      DESIGN AND SETTING: Cross-sectional study, conducted in a university. METHODS:
      The study included 564 children and adolescents, aged 8 to 17 years. Body mass
      index and waist circumference were used to evaluate obesity. Other cardiovascular
      risk factors were evaluated, like systolic and diastolic blood pressure,
      glycemia, triglycerides and total cholesterol. Descriptive analysis was used for
      sample characterization, the chi-square test for categorical variables and
      Pearson's linear correlation for evaluating the relationship between obesity
      indicators and other cardiovascular risk factors. RESULTS: High prevalence of
      overweight/obesity was found among the schoolchildren (25.3% among the boys and
      25.6% among the girls), along with abdominal obesity (19.0%). The
      overweight/obese schoolchildren presented higher percentages for the pressure and
      biochemical indicators, compared with underweight and normal-weight
      schoolchildren. Body mass index and waist circumference showed a weak correlation
      with the variables of age and systolic and diastolic blood pressure (P < 0.001),
      but there was no correlation between these obesity indices and biochemical
      variables. CONCLUSION: The high prevalence of overweight/obesity and its
      relationship with other cardiovascular risk factors demonstrate that it is
      necessary to develop intervention and prevention strategies from childhood
      onwards, in order to avoid development of chronic-degenerative diseases in
      adulthood.

PMID- 24310802
TI  - Effect of ambulatory versus hospital treatment for gestational diabetes or
      hyperglycemia on infant mortality rates: a systematic review.
AB  - CONTEXT AND OBJECTIVE: Pregnancies complicated by diabetes are associated with
      increased neonatal and maternal complications. The most serious maternal
      complication is the risk of developing type 2 diabetes, 10-12 years after the
      delivery. For rigorous control over blood glucose, pregnant women are treated
      through ambulatory management or hospitalization. The aim of this study was to
      evaluate the effectiveness of ambulatory management versus hospitalization in
      pregnancies complicated by diabetes or hyperglycemia. DESIGN AND SETTING:
      Systematic review conducted in a public university hospital. METHODS: A
      systematic review of the literature was performed and the main electronic
      databases were searched. The date of the most recent search was September 4,
      2011. Two authors independently selected relevant clinical trials, assessed their
      methodological quality and extracted data. RESULTS: Only three studies were
      selected, with small sample sizes. There was no statistically significance
      different between ambulatory management and hospitalization, regarding mortality
      in any of the subcategories analyzed: perinatal and neonatal deaths (relative
      risk [RR] 0.65; 95% confidential interval [CI]: 0.11 to 3.84; P = 0.63); neonatal
      deaths (RR 0.29; 95% CI: 0.01 to 6.07; P = 0.43); and infant deaths (RR 0.29; 95%
      CI: 0.01 to 6.07; P = 0.43). CONCLUSIONS: This review, based on studies with high
      or moderate risk of bias, showed that there was no statistically significant
      difference between ambulatory management and hospital care, regarding reduction
      of mortality rates in pregnancies complicated by diabetes or hyperglycemia. It
      also suggested that there is a need for further randomized controlled trials on
      this issue.

PMID- 24310803
TI  - Prediction of sepsis-related outcomes in neonates through systematic genotyping
      of polymorphisms in genes for innate immunity and inflammation: a narrative
      review and critical perspective.
AB  - CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and
      maternal infection. Large-scale studies seek to define markers that identify
      neonates at risk of developing sepsis. Here, we examine whether the scientific
      evidence supports systematic use of polymorphism genotyping in cytokine and
      innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN
      AND SETTING: Narrative literature review conducted at Fernandes Figueira
      Institute, Brazil. METHODS: The literature was searched in PubMed, Embase
      (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em
      Ciencias da Saude), SciELO (Scientific Electronic Library Online) and Cochrane
      Library. From > 400,000 references, 548 were retrieved based on
      inclusion/exclusion criteria; 22 were selected for detailed analysis after
      quality assessment. RESULTS: The studies retrieved addressed the impact of gene
      polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL
      1beta, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and
      angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite
      initial reports suggesting positive associations between specific polymorphisms
      and increased risk of sepsis, the accumulated evidence has not confirmed that any
      of them have predictive power to justify systematic genotyping. CONCLUSIONS:
      Sepsis prediction through systematic genotyping needs to be reevaluated, based on
      studies that demonstrate the functional impact of gene polymorphisms and
      epidemiological differences among ethnically distinct populations.

PMID- 24310804
TI  - Tuberous sclerosis complex diagnosed from oral lesions.
AB  - CONTEXT: Tuberous sclerosis complex (TSC) is a genetic disease in the group known
      as neurocutaneous syndromes, with dominant autosomal inheritance. It is
      characterized by skin and adnexal lesions and central and peripheral nervous
      system tumors, with neurological and psychiatric findings. It may affect the
      heart, kidneys, eyes, face, bones, lungs, stomach and dentition. CASE REPORT: We
      present the case of a 66-year-old man with dermatological signs that included
      hypopigmented maculae, confetti-like lesions, shagreen plaque, angiofibromas on
      nasolabial folds, neck and back, nail dystrophy and periungual fibromas on
      fingers and toes. An electroencephalogram produced normal results, but magnetic
      resonance imaging showed a nodular image measuring 1.2 x 1.0 cm close to the
      Monro foramen, which was similar to cerebral parenchyma and compatible with a
      subependymal giant-cell astrocytoma. A conservative approach was taken, through
      control imaging examinations on the lesion for seven years, with absence of any
      expansive process or neurological symptoms. Abdominal ultrasonography revealed a
      solid, heterogenic and echogenic mass with a calcified focus, measuring 4.6 x 3.4
      cm, in the rightkidney, compatible with angiomyolipoma. The patient was treated
      by means of complete nephrectomy because of malignant areas seen on
      histopathological examination and died one month after the procedure. This case
      report illustrates the importance of oral clinical findings such as dental enamel
      pits and angiofibromas in making an early diagnosis of TSC, with subsequent
      screening examinations, treatment and genetic counseling.

PMID- 24310805
TI  - Renal artery pseudoaneurysm after blunt renal trauma: report on three cases and
      review of the literature.
AB  - CONTEXT: Renal artery pseudoaneurysm is a rare complication after renal injury
      but should be suspected whenever there is recurrent hematuria after renal trauma.
      CASE REPORTS: We present three cases of pseudoaneurysm after blunt renal trauma
      and a review of the literature. All patients underwent renal angiography. Two
      cases were diagnosed during the initial hospital stay due to hematuria, or in the
      follow-up period during recovery. One patient was hemodynamically unstable. Two
      patients successfully underwent coil embolization in a single session. In the
      other case, selective embolization was attempted, but was unsuccessful because
      artery catheterization was impossible. Procedural and medical success and
      complications were retrospectively assessed from the patients' records. The
      clinical presentation, treatment options and clinical decisions are discussed.
      CONCLUSIONS: Renal artery pseudoaneurysm may develop acutely or even years after
      the initial injury. Signs and symptoms may have a wide spectrum of presentation.
      Selective angiographic embolization is an effective treatment that reduces the
      extent of parenchymal infarction.

PMID- 24310806
TI  - Cranberries for preventing urinary tract infections.
AB  - BACKGROUND: Cranberries have been used widely for several decades for the
      prevention and treatment of urinary tract infections (UTIs). This is the third
      update of our review first published in 1998 and updated in 2004 and 2008.
      OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs
      in susceptible populations. METHODS:  SEARCH METHODS: We searched MEDLINE,
      EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The
      Cochrane Library) and the Internet. We contacted companies involved with the
      promotion and distribution of cranberry preparations and checked reference lists
      of review articles and relevant studies. Date of search: July 2012. SELECTION
      CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry
      products for the prevention of UTIs. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed and extracted data. Information was collected on methods,
      participants, interventions and outcomes (incidence of symptomatic UTIs, positive
      culture results, side effects, adherence to therapy). Risk ratios (RR) were
      calculated where appropriate, otherwise a narrative synthesis was undertaken.
      Quality was assessed using the Cochrane risk of bias assessment tool. MAIN
      RESULTS: This updated review includes a total of 24 studies (six cross-over
      studies, 11 parallel group studies with two arms; five with three arms, and two
      studies with a factorial design) with a total of 4473 participants. Ten studies
      were included in the 2008 update, and 14 studies have been added to this update.
      Thirteen studies (2380 participants) evaluated only cranberry juice/concentrate;
      nine studies (1032 participants) evaluated only cranberry tablets/capsules; one
      study compared cranberry juice and tablets; and one study compared cranberry
      capsules and tablets. The comparison/control arms were placebo, no treatment,
      water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were
      not included in the meta-analyses because either the design was a cross-over
      study and data were not reported separately for the first phase, or there was a
      lack of relevant data. Data included in the meta-analyses showed that, compared
      with placebo, water or not treatment, cranberry products did not significantly
      reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04)
      or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to
      1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95%
      CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22);
      cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder
      or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was
      moderate (I2 = 55%). The effectiveness of cranberry was not significantly
      different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR
      0.69 95% CI 0.32 to 1.51). There was no significant difference between
      gastrointestinal adverse effects from cranberry product compared to those of
      placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low
      compliance and high withdrawal/dropout problems which they attributed to
      palatability/acceptability of the products, primarily the cranberry juice. Most
      studies of other cranberry products (tablets and capsules) did not report how
      much of the 'active' ingredient the product contained, and therefore the products
      may not have had enough potency to be effective. AUTHORS' CONCLUSIONS: Prior to
      the current update it appeared there was some evidence that cranberry juice may
      decrease the number of symptomatic UTIs over a 12 month period, particularly for
      women with recurrent UTIs. The addition of 14 further studies suggests that
      cranberry juice is less effective than previously indicated. Although some of
      small studies demonstrated a small benefit for women with recurrent UTIs, there
      were no statistically significant differences when the results of a much larger
      study were included. Cranberry products were not significantly different to
      antibiotics for preventing UTIs in three small studies. Given the large number of
      dropouts/withdrawals from studies (mainly attributed to the acceptability of
      consuming cranberry products particularly juice, over long periods), and the
      evidence that the benefit for preventing UTI is small, cranberry juice cannot
      currently be recommended for the prevention of UTIs. Other preparations (such as
      powders) need to be quantified using standardised methods to ensure the potency,
      and contain enough of the 'active' ingredient, before being evaluated in clinical
      studies or recommended for use.

PMID- 24310808
TI  - Notice of retraction.

PMID- 24310807
TI  - Immersion in water in labour and birth.
AB  - BACKGROUND: Enthusiasts suggest that labouring in water and waterbirth increase
      maternal relaxation, reduce analgesia requirements and promote a midwifery model
      of care. Critics cite the risk of neonatal water inhalation and maternal/neonatal
      infection. OBJECTIVES: To assess the evidence from randomised controlled trials
      about immersion in water during labour and waterbirth on maternal, fetal,
      neonatal and caregiver outcomes. METHODS:  SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2011) and
      reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled
      trials comparing immersion in any bath tub/pool with no immersion, or other non
      pharmacological forms of pain management during labour and/or birth, in women
      during labour who were considered to be at low risk of complications, as defined
      by the researchers. DATA COLLECTION AND ANALYSIS: We assessed trial eligibility
      and quality and extracted data independently. One review author entered data and
      the other checked for accuracy. MAIN RESULTS: This review includes 12 trials
      (3,243 women): 8 related to just the first stage of labour: one to early versus
      late immersion in the first stage of labour; two to the first and second stages;
      and another to the second stage only. We identified no trials evaluating
      different baths/pools, or the management of third stage of labour. Results for
      the first stage of labour showed there was a significant reduction in the
      epidural/spinal/paracervical analgesia/anaesthesia rate amongst women allocated
      to water immersion compared to controls (478/1,254 versus 529/1,245; risk ratio
      (RR) 0.90; 95% confidence interval (CI) 0.82 to 0.99, six trials). There was also
      a reduction in duration of the first stage of labour (mean difference -32.4
      minutes; 95% CI -58.7 to -6.13). There was no difference in assisted vaginal
      deliveries (RR 0.86; 95% CI 0.71 to 1.05, seven trials), caesarean sections (RR
      1.21; 95% CI 0.87 to 1.68, 8 trials), use of oxytocin infusion (RR 0.64; 95% CI
      0.32 to 1.28, 5 trials), perineal trauma or maternal infection. There were no
      differences for Apgar score less than 7 at 5 minutes (RR 1.58; 95% CI 0.63 to
      3.93, 5 trials), neonatal unit admissions (RR 1.06; 95% CI 0.71 to 1.57, three
      trials), or neonatal infection rates (RR 2.00; 95% CI 0.50 to 7.94, five trials).
      Of the 3 trials that compared water immersion during the second stage with no
      immersion, one trial showed a significantly higher level of satisfaction with the
      birth experience (RR 0.24; 95% CI 0.07 to 0.80). A lack of data for some
      comparisons prevented robust conclusions. Further research is needed. AUTHORS'
      CONCLUSIONS: Evidence suggests that water immersion during the first stage of
      labour reduces the use of epidural/spinal analgesia and duration of the first
      stage of labour. There is limited information for other outcomes related to water
      use during the first and second stages of labour, due to intervention and outcome
      variability. There is no evidence of increased adverse effects to the
      fetus/neonate or woman from labouring in water or waterbirth. However, the
      studies are very variable and considerable heterogeneity was detected for some
      outcomes. Further research is needed.

PMID- 24310809
TI  - Effect of a diet and physical activity intervention on body weight and
      nutritional patterns in overweight and obese breast cancer survivors.
AB  - Energy restriction from a low-calorie diet and increased energy expenditure
      induced by physical activity (PA) could promote weight loss/maintenance and be
      important determinants of breast cancer (BC) prognosis. The aim of this study was
      to assess participation and adherence of overweight and obese BC survivors to a
      lifestyle intervention and to demonstrate the capacity of this intervention to
      induce weight loss and nutritional changes. This single-arm pre-post study, which
      involved one-hourly weekly diet sessions delivered by a dietician and 75-min bi
      weekly PA sessions of moderate-to-high intensity led by PA monitors, was offered
      to overweight and obese BC survivors shortly after treatment. Before and after
      the intervention, anthropometry, dietary information, quality of life (QoL) and
      cardiorespiratory fitness (CRF) were collected. A total of 112 BC survivors were
      invited to participate: 42 of them started the intervention and 37 completed it.
      Participants attended more than 90 % of the sessions offered and showed a
      significant weight loss of 5.6 +/- 2.0 kg, as well as significant decreases in
      body mass index, fat mass and waist circumference. Significant decreases in total
      energy (-25 %), fat (-35 %), saturated fat (-37 %) and carbohydrate (-21 %)
      intakes were observed while QoL and CRF showed significant increases. This
      feasibility study demonstrated the success of a short-term diet and PA
      intervention to induce weight loss and promote healthful changes in BC survivors.
      Assessing the long-term effects of these changes, and in particular their
      possible impact of BC prognosis, and designing interventions reaching a wider
      number of BC survivors are still issues to be addressed.

PMID- 24310810
TI  - The Glasgow Prognostic Score accurately predicts survival in patients with
      biliary tract cancer not indicated for surgical resection.
AB  - The Glasgow Prognostic Score (GPS) and neutrophil to lymphocyte ratio (NLR) are
      associated with the survival in patients with various types of malignancy. The
      aim of this study was to investigate the prognostic value of the GPS and NLR in
      patients with biliary tract cancer (BTC) undergoing palliative chemotherapy or
      best supportive care (BSC). Fifty-two patients with newly diagnosed BTC were
      retrospectively evaluated. We investigated the correlation between the GPS, NLR,
      and the overall survival rates. The area under the receiver operating
      characteristics curve (AUC) was calculated to compare the predictive ability of
      each score. Both the univariate and multivariate analyses were performed to
      identify clinicopathological variables associated with the overall survival.
      There were significant differences between the GPS groups regarding the
      neutrophil levels (p < 0.0001), Hb (p = 0.024), Alb (p < 0.0001) and CRP (p <
      0.0001). A significant difference in the overall survival was found between the
      groups stratified based on the GPS, NLR (p < 0.001). The GPS had a higher AUC
      value (0.905) in comparison to the NLR (0.648). In the multivariate analysis, the
      sex (p = 0.002), CA19-9 (p < 0.0001) and the GPS (p < 0.0001) were found to be
      independently associated with the overall survival. Our results demonstrate that
      the GPS is an independent marker of the prognosis in patients with BTC undergoing
      palliative chemotherapy or BSC, and is superior to the NLR in terms of its
      prognostic ability.

PMID- 24310811
TI  - MACC1 overexpression predicts a poor prognosis for non-small cell lung cancer.
AB  - The expression of metastasis-associated in colon cancer-1 (MACC1) in non-small
      cell lung cancer (NSCLC) and its association with pathological characteristics
      and prognosis for NSCLC patients were investigated retrospectively. The
      expression of MACC1 was evaluated through immunohistochemical staining of tissue
      microarrays from 180 samples of resected lung cancer tissues and adjacent normal
      lung tissues. MACC1 protein and mRNA expression were also examined from lung
      cancer cell lines with different metastatic potentials, 28 pairs of samples of
      resected fresh non-small cell lung cancer tissues, and adjacent normal lung
      tissues. Immunohistochemical staining of tissue microarrays showed that MACC1 was
      located in the cytoplasm. In addition, the expression of MACC1 protein in NSCLC
      was significantly higher compared to adjacent normal tissues (P < 0.001). The
      expression of MACC1 was positively associated with differentiation grade (P =
      0.020), postoperative pathological TNM stage (P = 0.033), and lymph node
      metastasis (P = 0.028). Disease-free survival (DFS) and overall survival (OS) for
      the high MACC1 expression group were lower than the low expression group;
      univariate and multivariate regression analyses showed that MACC1 was an
      independent prognostic indicator for DFS (HR 3.124, P = 0.01) and OS (HR 2.905, P
      = 0.01) in NSCLC patients. The expression of MACC1 protein and mRNA was also
      upregulated in highly metastatic human lung cancer. In conclusion, the
      overexpression of MACC1 protein and mRNA may represent a potentially useful
      biomarker for the prognosis of NSCLC patients and might be involved in
      progression of NSCLC.

PMID- 24310812
TI  - Prediction of local recurrence in cervical cancer by a Cox model comprised of
      lymph node status, lymph-vascular space invasion, and intratumoral Th17 cell
      infiltration.
AB  - The identification of cervical cancer patients at high risk of local recurrence
      is urgent to improve the selection of patients for more aggressive treatment. The
      immune contexture in human tumors has vital impact on clinical outcome. Our aim
      in the study was to establish a predictive model of local recurrence by assessing
      the prognostic significance of clinicopathologic features and five immune markers
      within the tumor microenvironment in cervical cancer. The expression of CD3, CD4,
      CD8, FoxP3, and IL-17 was assessed by immunohistochemistry in tumor tissue from
      153 patients after radical resection for cervical cancer. Prognostic effects of
      these immune markers and clinicopathologic factors were evaluated by Kaplan-Meier
      and Cox regression analysis. Local recurrence was observed in 34 % patients
      (52/153). Independent predictors of tumor recurrence were lymph node status (P =
      0.004), lymph-vascular space invasion (P = 0.012), and the number of intratumoral
      IL-17(+) cells (P = 0.003). The risk of local recurrence was the highest in
      patients with lymph node positivity, presence of lymph-vascular space invasion,
      and low prevalent of intratumoral IL-17(+) cells (probability, 73 %; 5-year DFS,
      19 %). A Cox model composed of these three features provided a significant higher
      diagnostic accuracy of local recurrence than each feature alone (P < 0.05). Lymph
      node status, lymph node space invasion, and number of intratumoral IL-17(+) cells
      are three independent predictors for recurrence of cervical cancer. Their
      combination by a Cox model is highly predictive and may help to identify high
      risk patients who may benefit from adjuvant chemotherapy.

PMID- 24310813
TI  - Predicting distant metastasis and chemoresistance using plasma miRNAs.
AB  - In the clinic, predicting metastasis and chemoresistance takes high priority, but
      has not been well established. This study seeks to investigate whether
      dynamically monitoring serum microRNAs (miRNAs) can help predict metastasis,
      chemoresistance, and prognosis of colorectal cancer. Serum miR-155, miR-200c, and
      miR-210 levels in 15 patients with colon cancer were measured by real-time PCR at
      different time points post surgery and chemotherapy for 3 years. Significant
      increases in miR-155, miR-200c, and miR-210 levels were observed in the serum and
      tumor tissues of colon cancer patients compared to that of healthy subjects.
      After surgery and chemotherapy, the serum levels of these miRNAs in patients with
      good prognosis returned to normal levels found in healthy controls during the 3
      year follow-up. In patients with recurrence and distant metastasis, serum miR
      155, miR-200c, and miR-210 levels remained at an elevated level or became
      elevated again after a short period of decline. In patients with good response to
      chemotherapy for metastatic tumors, re-elevation of miR-155 was not significant
      compared to miR-200c and miR-210. In contrast, miR-155 re-elevated more
      significantly in patients not sensitized to chemotherapy than miR-200c and miR
      210. Our study suggests that re-elevation or sustained elevation of serum miR-155
      level after surgery and chemotherapy is a sign of chemoresistance in colon
      cancer, while high and/or re-elevated miR-155, miR-200c, and miR-210 levels
      implicate local recurrence and distant metastasis as well as poor prognosis.

PMID- 24310815
TI  - Cardiac outflow tract development relies on the complex function of Sox4 and
      Sox11 in multiple cell types.
AB  - Congenital heart defects represent the most common human birth defects and are
      often life-threatening. Frequently, they are caused by abnormalities of the
      outflow tract whose formation results from coordinated development of cells from
      mesodermal and neural crest origin and depends on the activity of many different
      transcription factors. However, place, time, and mode of action have only been
      analyzed for a few of them. Here we assess the contribution of the closely
      related high-mobility-group transcription factors Sox4 and Sox11 to outflow tract
      development and determine their function. Using cell-type-specific deletion in
      the mouse, we show that Sox11 is required for proper development in both
      mesodermal cells and neural crest cells. Deletion in either mesoderm or neural
      crest, or both, leads to outflow tract defects ranging from double outlet right
      ventricle to common arterial trunk. Sox4 supports Sox11 in its function, but has
      additional roles with relevance for outflow tract formation in other cell types.
      The two Sox proteins are dispensable during early phases of cardiac neural crest
      development including neural tube emigration, proliferation, and migration
      through the pharyngeal arches. They become essential after arrival of the neural
      crest cells in the outflow tract for their proper differentiation and interaction
      with each other as well as with the environment through regulation of
      cytoskeletal, cell adhesion, and extracellular matrix molecules. Our results
      demonstrate that Sox4 and Sox11 have multiple functions in several cell types
      during outflow tract formation and may thus help to understand the basis of
      congenital heart defects in humans. 

PMID- 24310816
TI  - Outcome of pulmonary vein isolation ablation for paroxysmal atrial fibrillation:
      predictive role of left atrial mechanical dyssynchrony by speckle tracking
      echocardiography.
AB  - INTRODUCTION: Although few clinical variables have been associated with
      recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) the
      role of left atrial (LA) mechanical function in the outcome of catheter ablation
      of AF is not adequately defined. The aim of our study was to determine whether LA
      mechanical dyssynchrony as evaluated by speckle tracking echocardiography can
      predict outcome of PVI ablation procedure in patients with paroxysmal AF.
      METHODS: Twenty-five patients (age 58 +/- 11 years, [mean +/- standard
      deviation], 17 males) with paroxysmal AF who met specific enrollment criteria
      pertaining to clinical presentation and follow-up, assessment of LA mechanical
      dyssynchrony, and strategy of catheter ablation procedure were enrolled. For LA
      mechanical dyssynchrony assessment, the time to peak longitudinal strain (TPk) in
      opposing walls in the midportion of the LA walls at peak atrial contraction in
      standard two- and four-chamber echocardiographic views by vector velocity imaging
      (VVI) was measured. Outcome of PVI procedure, whether no recurrence (NR) or AF
      recurrence (AFR) after 3 months of post-procedural blanking period, was evaluated
      based on AF-related symptoms and documentation of AF by electrocardiogram,
      continuous 24-h Holter, and intermittent event monitor recordings. RESULTS:
      During a follow-up period of 20.3 +/- 8.6 months, 18 out of 25 (72 %) patients
      had no recurrence (NR group), and 7 out of 25 (28 %) patients had recurrence of
      AF (AFR group). Significant gender difference was observed in terms of outcome
      such that all AFR patients were men and no woman had recurrence of AF. Between
      the NR and AFR groups, neither the left atrial diameter, 4.0 +/- 0.3 and 4.2 +/-
      0.2 cm, respectively (p = 0.2), nor the left atrial volume indexes, 45 +/- 15 and
      48 +/- 20 ml/m(2), respectively (p = 0.56), were statistically significantly
      different. For LA mechanical function, compared to the patients in NR group who
      had maximum opposing wall TPk delay of 39.9 +/- 12.0 ms, those in the AFR group
      demonstrated significantly more LA mechanical dyssynchrony with maximum opposing
      wall TPk delay of 64.4 +/- 17.0 ms prior to ablation (p = 0.007). Using receiver
      operative characteristic analyses of the data that had an area under the curve of
      0.865, we identified a maximum opposing wall delay cutoff value of 51 ms which
      predicted AF recurrence with sensitivity and specificity values of 89 and 72 %,
      respectively (p = 0.005). CONCLUSIONS: Speckle tracking strain analysis
      echocardiography can evaluate the LA mechanical dyssynchrony quantitatively. The
      severity of LA mechanical dyssynchrony by VVI can predict the outcome of PVI
      catheter ablation for paroxysmal AF.

PMID- 24310814
TI  - Histone deacetylase signaling in cardioprotection.
AB  - Cardiovascular disease (CVD) represents a major challenge for health care
      systems, both in terms of the high mortality associated with it and the huge
      economic burden of its treatment. Although CVD represents a diverse range of
      disorders, they share common compensatory changes in the heart at the structural,
      cellular, and molecular level that, in the long term, can become maladaptive and
      lead to heart failure. Treatment of adverse cardiac remodeling is therefore an
      important step in preventing this fatal progression. Although previous efforts
      have been primarily focused on inhibition of deleterious signaling cascades, the
      stimulation of endogenous cardioprotective mechanisms offers a potent therapeutic
      tool. In this review, we discuss class I and class II histone deacetylases, a
      subset of chromatin-modifying enzymes known to have critical roles in the
      regulation of cardiac remodeling. In particular, we discuss their molecular modes
      of action and go on to consider how their inhibition or the stimulation of their
      intrinsic cardioprotective properties may provide a potential therapeutic route
      for the clinical treatment of CVD. 

PMID- 24310817
TI  - Clustering of genomic breakpoints at the MLL locus in therapy-related acute
      leukemia with t(4;11)(q21;q23).
AB  - Genomic characterization of translocation breakpoints is relevant to identify
      possible mechanisms underlying their origin. The consistent association of
      anthracylines (e.g., epirubicin and idarubicin) in inducing therapy-related acute
      leukemias (t-AL) with mixed lineage leukemia (MLL) gene rearrangement suggests
      that MLL translocations are causative events for t-AL. Using asymmetric multiplex
      PCR strategy followed by direct DNA sequencing, we characterized the genomic
      breakpoints of the MLL and AFF1 genes in two patients who developed t-AL with
      t(4;11)(q21;q23). Chemotherapeutic treatment of the primary disease in both
      patients included topoisomerase II (topo II) targeting agents. In one case, the
      MLL breakpoint was located in intron 9 at nucleotide position chr11:118354284
      while the AFF1 breakpoint was in intron 3 at nucleotide position chr4:87992070.
      The breakpoint junction sequences revealed an insertion of two nucleotides at the
      MLL-AFF1 junction. In the other patient, the MLL breakpoint was located in intron
      11 at nucleotide position chr11:118359130-32 and the AFF1 break was in intron 3
      at nucleotide position chr4:87996215-17. The MLL breakpoint found in the latter
      patient was identical to that of two previously reported cases, strongly
      suggesting the presence of a preferential site of DNA cleavage in the presence of
      topo II inhibitor. In addition, microhomologies at the breakpoint junctions were
      indicative of DNA repair by the non-homologous end joining (NHEJ) pathway. This
      study further supports the evidence that MLL breakpoints in therapy-related acute
      leukemia with MLL-AFF1 are clustered in the telomeric half of the breakpoint
      cluster region that contains topo II recognition sites.

PMID- 24310818
TI  - Physiological reactivity in a community sample of sexually aggressive young men:
      a test of competing hypotheses.
AB  - Men's sexually aggressive behavior potentially could relate to either
      physiological hyporeactivity or hyperreactivity, and these two different
      physiological profiles could be associated with different underlying causes of
      sexual aggression. Thus, measurement of physiological reactivity could provide
      insight into mechanisms relevant to the etiology of sexual aggression. The
      relationship between sexual aggression and physiological reactivity was
      investigated in 78 community men (38 sexually aggressive and 40 non-aggressive
      men). In a laboratory protocol, the men were exposed to neutral, negative-affect
      inducing, and positive-affect-inducing stimuli. Men's salivary cortisol
      concentrations and electrodermal activity (EDA) were measured throughout the
      laboratory procedure. Sexually aggressive men demonstrated (1) lower overall
      cortisol levels and (2) lower EDA reactivity in some conditions as compared to
      non-aggressive men. Results of this study were consistent with the idea that
      men's sexual aggression is associated with physiological hyporeactivity, a
      physiological profile that has been found to be associated with externalizing
      behaviors and psychopathic traits.

PMID- 24310819
TI  - 157 nm photodissociation of dipeptide ions containing N-terminal arginine.
AB  - Twenty singly-charged dipeptide ions with N-terminal arginine were
      photodissociated using 157 nm light in both a linear ion-trap mass spectrometer
      and a MALDI-TOF-TOF mass spectrometer. Analogous to previous work on dipeptides
      containing C-terminal arginine, this set of samples enabled insights into the
      photofragmentation propensities associated with individual residues. In addition
      to familiar products such as a-, d-, and immonium ions, m2 and m2+13 ions were
      also observed. Certain side chains tended to cleave between their beta and gamma
      carbons without necessarily forming d- or w-type ions, and a few other ions were
      produced by the high-energy fragmentation of multiple bonds.

PMID- 24310822
TI  - Urolithiasis in an infant with propionic acidemia: questions.

PMID- 24310821
TI  - Cardiac myosin binding protein-C: a novel sarcomeric target for gene therapy.
AB  - Through its ability to interact with both the thick and thin filament proteins
      within the sarcomere, cardiac myosin binding protein-C (cMyBP-C) regulates the
      contractile properties of the myocardium. The central regulatory role of cMyBP-C
      in heart function is emphasized by the fact that a large proportion of inherited
      hypertrophic cardiomyopathy cases in humans are caused by mutations in cMyBP-C.
      The primary dysfunction in cMyBP-C-related cardiomyopathies is likely to be
      abnormal myofilament contractile function; however, currently, there are no
      effective therapies for ameliorating these contractile defects. Thus, there is a
      compelling need to design novel therapies to restore normal contractile function
      in cMyBP-C-related cardiomyopathies. To this end, concepts gleaned from various
      structural, functional, and biochemical studies can now be utilized to engineer
      cMyBP-C proteins that, when incorporated into the sarcomere, can significantly
      improve contractile function. In this review, we discuss the rationale for cMyBP
      C-based gene therapies that can be utilized to treat contractile dysfunction in
      inherited and acquired cardiomyopathies. 

PMID- 24310820
TI  - The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and
      blood pressure regulation.
AB  - SLC12A3 encodes the thiazide-sensitive sodium chloride cotransporter (NCC), which
      is primarily expressed in the kidney, but also in intestine and bone. In the
      kidney, NCC is located in the apical plasma membrane of epithelial cells in the
      distal convoluted tubule. Although NCC reabsorbs only 5 to 10% of filtered
      sodium, it is important for the fine-tuning of renal sodium excretion in response
      to various hormonal and non-hormonal stimuli. Several new roles for NCC in the
      regulation of sodium, potassium, and blood pressure have been unraveled recently.
      For example, the recent discoveries that NCC is activated by angiotensin II but
      inhibited by dietary potassium shed light on how the kidney handles sodium during
      hypovolemia (high angiotensin II) and hyperkalemia. The additive effect of
      angiotensin II and aldosterone maximizes sodium reabsorption during hypovolemia,
      whereas the inhibitory effect of potassium on NCC increases delivery of sodium to
      the potassium-secreting portion of the nephron. In addition, great steps have
      been made in unraveling the molecular machinery that controls NCC. This complex
      network consists of kinases and ubiquitinases, including WNKs, SGK1, SPAK, Nedd4
      2, Cullin-3, and Kelch-like 3. The pathophysiological significance of this
      network is illustrated by the fact that modification of each individual protein
      in the network changes NCC activity and results in salt-dependent hypotension or
      hypertension. This review aims to summarize these new insights in an integrated
      manner while identifying unanswered questions.

PMID- 24310824
TI  - Molecular Absorbent Recirculating System therapy (MARS(r)) in pediatric acute
      liver failure: a single center experience.
AB  - BACKGROUND: Supportive care as a bridge to transplant or recovery remains
      challenging in children suffering from acute liver failure (ALF). We report our
      experience in children using the Molecular Absorbent Recirculating System
      (MARS((r))). METHODS: Retrospective data from children receiving therapy using
      MARS((r)) from October 2009 to October 2012 were included in this single-center
      retrospective study. Patient characteristics, clinical presentation and
      complications of ALF, clinical and biological data before and after each
      MARS((r)) session, technical modalities and adverse events were recorded.
      RESULTS: A total of six children underwent 17 MARS((r)) sessions during the study
      period. Two adolescents were treated with the adult filter MARSFLUX((r)) and four
      infants were treated with the MiniMARS((r)) filter. The mean PEdiatric Logistic
      Dysfunction (PELOD) score at admission was 19 (range 11-33). All patients were
      mechanically ventilated, and four had acute kidney injury. The neurological
      course improved in one case, judged as stable in two cases and worsened in one
      case; data were unavailable in two cases. Mean serum ammonia levels decreased
      significantly following treatment with MARS((r)) from an initial 89 +/- 29 to 58
      +/- 35 mcmol/L (p = 0.02). No other significant biological improvement was
      observed. Hemodynamic status improved/remained unchanged in the adolescent group,
      but in the infants four of the seven sessions were poorly tolerated and two
      sessions were aborted. Three patients died, two were successfully transplanted
      and one recovered without transplantation. CONCLUSION: In our experience,
      treatment with MARS((r)) is associated with encouraging results in adolescents,
      but it needs modification for very sick infants to improve tolerance.

PMID- 24310826
TI  - Dual-energy CT immediately after endovascular stroke intervention: prognostic
      implications.
AB  - PURPOSE: Posttreatment intracerebral hemorrhage (ICH) after recanalization
      therapy of acute ischemic stroke increases morbidity and mortality. Dual-energy
      (DE) computed tomography (CT) allows differentiation of blood-brain barrier
      disruption (BBBD) and ICH. We evaluated the incidence of ICH and BBBD immediately
      after endovascular recanalization therapy, the correlation between BBBD and final
      infarction or ICH size, and the prognostic value of postinterventional BBBD.
      METHODS: Imaging data sets (pretreatment CT, posttreatment DE-CT, and follow-up
      imaging by CT and/or magnetic resonance imaging) of 60 consecutive patients after
      endovascular recanalization therapy of acute ischemic stroke were retrospectively
      analyzed. After material differentiation, areas of increase attenuation in
      posttreatment DE-CT were correlated to ICH and infarction in follow-up imaging.
      RESULTS: Areas of hyperattenuation were observed in 80.0 % (48 of 60) of all
      posttreatment CT. In 10.4 % (5 of 48) of these, hyperattenuating areas matched
      the hyperdensities on virtual nonenhanced CT and were rated as hemorrhage. The
      remaining 89.6 % (43 of 48) of scans with hyperattenuating areas demonstrated
      hyperdensities exclusively on iodine-only images and were rated as BBBD. All
      suspected ICH on DE-CT were proven in follow-up imaging. There were no false
      positive or false-negative findings of ICH in DE-CT. In 98.3 % (59 of 60) of
      cases, at least small ischemic infarctions were identified in follow-up imaging.
      No correlation between the extent of BBBD and the final infarct size and/or early
      ICH size was found. CONCLUSION: BBBD is a frequent finding after endovascular
      revascularization therapy. DE-CT allows for a reliable differentiation between
      frequent BBBD and rare ICH immediately after endovascular recanalization therapy.

PMID- 24310825
TI  - Nephrotic syndrome associated with tyrosine kinase inhibitors for pediatric
      malignancy: case series and review of the literature.
AB  - BACKGROUND: Tyrosine kinase (TK) inhibitors are increasingly being used to treat
      a variety of pediatric malignancies. Reports in adult patients describe a range
      of effects of TK inhibitors on the kidney, including hypertension, proteinuria,
      acute kidney injury, and thrombotic microangiopathy (TMA); however, there are
      only a few reports of TK-inhibitor-associated nephrotic syndrome. METHODS: We
      report four pediatric patients with various malignancies (chronic myelogenous
      leukemia, acute lymphoblastic leukemia, and glioma/renal cell carcinoma) who
      developed nephrotic syndrome during treatment with TK inhibitors (imatinib,
      sunitinib, dasatinib, and quizartinib). One of the four patients also had
      clinical features of TMA. RESULTS: Three of the four patients achieved complete
      remission of nephrotic syndrome with discontinuation of the TK inhibitor and have
      had no additional nephrotic syndrome relapses to date. The temporal relationship
      of nephrotic syndrome onset to TK-inhibitor therapy and resolution of nephrotic
      syndrome with cessation of therapy strongly imply an association in these
      patients. CONCLUSIONS: TK inhibitors are important therapies in pediatric cancer,
      and their use is expanding. Nephrotic syndrome with or without features of TMA is
      a potential complication of these therapies in children.

PMID- 24310827
TI  - Incidentally discovered uterine sarcoma in a premenopausal patient after
      hysterectomy for postembolization endometritis.
AB  - Uterine leiomyomas (fibroids) are the most common benign tumor of the female
      reproductive system. Fibroids can become symptomatic with symptoms such as
      menorrhagia and menometrorrhagia, pelvic pain, and reproductive dysfunction.
      Hysterectomy, myomectomy, and the less invasive uterine artery embolization are
      now commonly performed if conservative management of symptomatic fibroids fails.
      Moreover, uterine artery embolization (UAE) is the preferred minimally invasive
      procedure for the treatment of symptomatic fibroids. Major complications of UAE
      are extremely rare but well known. Additionally, there is a risk of undiagnosed
      uterine sarcoma found post embolization, which has been reported in literature
      during the past 12 years. Herein, we describe a case of an incidentally
      discovered uterine sarcoma in a premenopausal female after hysterectomy for post
      uterine artery embolization endometritis and sepsis. 

PMID- 24310828
TI  - Improved hypertrophy of future remnant liver after portal vein embolization with
      plugs, coils and particles.
AB  - PURPOSE: To retrospectively analyze efficacy as measured by volume gain of future
      remnant liver (FRL) after right portal vein embolization (PVE) using particles
      only versus particles and additional central plug and/or coil (CP/C)
      embolization. METHODS: All patients who underwent PVE between July 2011 and
      December 2012 were retrospectively analyzed. Right PVE was performed either with
      particle-only (PO) embolization or additional CP/C embolization. All enrolled
      patients underwent computed tomography or magnetic resonance imaging before PVE
      and surgery. The images were used for volumetry of the FRL. RESULTS: Of 75
      patients, 40 had PO and 35 CP/C embolization. Age, sex, and tumor entities did
      not differ significantly between the two groups. Tumor entities included
      cholangiocarcinoma (n = 52), metastasis from colorectal cancer (n = 14),
      hepatocellular carcinoma (n = 2), and others (n = 7). Time from PVE to
      preoperative imaging was similar in both groups. FRL volume before PVE was 329 +/
      121 ml in the PO group and 333 +/- 135 ml in the CP/C group, and 419 +/- 135 ml
      and 492 +/- 165 ml before operation. The average percentage volume gain was
      significantly higher in the CP/C group than in the PO group, with 53.3 +/- 34.5 %
      versus 30.9 +/- 28.8 % (p = 0.002). CONCLUSION: Right PVE with additional CP/C
      embolization leads to a significantly higher gain in FRL volume than embolization
      with particles alone.

PMID- 24310829
TI  - Family perceptions of adolescent self-image.
AB  - This study examined relationships between adolescents' self-image and perceptions
      of these adolescents held by their parents. It was hypothesized that parents
      would generally agree with their children's self-perceptions and that greater
      congruence between parents and their children would be associated with greater
      positive adolescent self-image. One hundred and six normal families participated
      in this study in the spring of 1981. Results showed that parents accurately
      perceive their adolescent children's selfimage. Specific areas of disagreement
      between parents and adolescents are discussed. Other results showed that mother
      father agreement is associated with positive descriptions by the adolescents of
      their family and a positive attitude toward vocational and educational goals.
      Mother-child congruence scores were more highly correlated with adolescents' self
      image than fatherchild congruence scores. Daughters' self-image was more highly
      associated with parent-child agreement than was sons' self-image. 

PMID- 24310830
TI  - Personality structure and identity status in women as viewed through early
      memories.
AB  - Early memories were obtained from women in the four identity status categories
      and rated for developmental level in an effort to assess deeper aspects of
      personality development that underlie identity formation. In contrast to some
      previous research which has found similarities between Achievement and
      Foreclosure women and between Moratorium and Diffusion women, this study found
      that Moratorium women show greater ego development in contrast to the
      Foreclosures. Achievement women were found to blend aspects of both Foreclosure
      and Moratorium patterns, suggesting that their approach to identity formation may
      be through a form of rapprochement. 

PMID- 24310831
TI  - Adolescents at home: An exploratory study of the relationship between perception
      of family social climate, general well-being, and actual behavior in the home
      setting.
AB  - This study investigated the relationship between behavior in the home environment
      and perception of family social climate and personal well-being in a social
      ecological perspective. Participants in the study were 46 eighth-grade students,
      who provided information on their use of the home environment, their perception
      of family social climate through the Family Environment Scale (FES), and their
      sense of well-being through the General Well-Being Questionnaire (GWBQ). Multiple
      regression analyses revealed several strong relationships between the variables.
      First, and most important, a strong positive relationship between adolescents'
      sense of well-being and time spent with adults in leisure and recreational
      activities in the home was identified. Second, selected home setting "behaviors,"
      including watching television, were found to account for approximately 40% of the
      variance in adolescents' scores on the "Intellectual-Cultural Orientation"
      subscale of the FES. Implications were drawn for research on the relationship
      between perception of social climate, optimal human functioning, and actual
      behavior in specified settings. 

PMID- 24310832
TI  - Self-recognition of the face: A study of adolescent narcissism.
AB  - Two adolescent groups and an adult group were given a self-recognition task
      involving the tachistoscopic presentation of inverted photographs of their faces.
      Measures of narcissism, certainty of response, and response strategy were
      recorded. The young adolescent group was found to be more successful than either
      the late adolescent or adult groups. The former were also the most narcissistic.
      No sex difference was found, nor was there any difference when the faces of known
      or unknown peers were used as distractors. Age and narcissism were found to be
      equally good predictors of both self-recognition and certainty of response. Young
      adolescents tended to use the complete gestalt of the face more often as a
      recognition strategy than older adolescents or adults, who seemed to use
      idiosyncratic facial features. The results are discussed in terms of integrated
      approach to the development of body image and how the internal representations of
      the body are gradually built and modified by perceptual, cognitive, and
      personality functioning. 

PMID- 24310833
TI  - Adolescent deviation and age.
AB  - Traditional theories of delinquency causation generally fail to consider
      delinquency in the context of norms and age-role transitions peculiar to
      adolescence. Hence, in this study, an age-based theory of delinquency causation
      is developed, which assumes the importance of norms and roles specific to
      adolescence. This theory draws upon the assumption that socialization is
      recurrent, in contrast to the premises regarding socialization which underlie
      traditional theories of adolescent deviance. The recurrent model of socialization
      and that assumed by traditional theorists are discussed, and their implications
      for the causes of delinquent behavior are examined. Some effort is made to show
      that the recurrent model of socialization suggests an anomie of age as the basis
      for delinquent acts. It is suggested that this age-based anomie stems from
      conditions of normlessness associated with certain role transitions in
      adolescence and the pacing of these transitions. Further, it is suggested that
      certain groups are especially prone to an anomic age transition. The role
      transitions most likely to be subject to such anomic conditions and the
      adolescent subgroups most prone to experience anomie as a result of the pacing of
      their age-role transitions are identified. 

PMID- 24310834
TI  - Infrared spectra of protonated coronene and its neutral counterpart in solid
      parahydrogen: implications for unidentified interstellar infrared emission bands.
AB  - Large protonated polycyclic aromatic hydrocarbons (H(+) PAHs) are possible
      carriers of unidentified infrared (UIR) emission bands from interstellar objects,
      but the characterization of infrared (IR) spectra of large H(+) PAHs in the
      laboratory is challenging. IR absorption spectra of protonated coronene (1-C24
      H13 (+) ) and mono-hydrogenated coronene (1-C24 H13 (.) ), which were produced
      upon electron bombardment of parahydrogen containing a small proportion of
      coronene (C24 H12 ) during matrix deposition, were recorded. The spectra are of a
      much higher resolution than those obtained by IR multiphoton dissociation by
      Dopfer and co-workers. The IR spectra of protonated pyrene and coronene
      collectively appear to have the required chromophores for features of the UIR
      bands, and the spectral shifts on an increase in the number of benzenoid rings
      point in the correct direction towards the positions of the UIR bands. Larger
      protonated peri-condensed PAHs might thus be key species among the carriers of
      UIR bands. 

PMID- 24310835
TI  - Isolation and characterization of a gene encoding meso-diaminopimelate
      dehydrogenase fromGlycine max.
AB  - A detailed characterization of the lysine biosynthetic pathway in plants is yet
      to be completed. It is, however, assumed that the diaminopimelic acid pathway
      exists in the plant kingdom, as commonly described forEscherichia
      coli.Modification and refinement of lytic complementation, a technique previously
      utilized in bacterial systems, facilitated the isolation of a functional
      Diaminopimelate Dehydrogenase gene from aGlycine max nuclear gene library. The
      isolated gene codes for the enzyme meso-diaminopimelate dehydrogenase. The coding
      capacity for the enzyme was originally contained on a 6.6kb fragment in a Charon
      4a soybean gene bank. Subcloning of the 6.6kb fragment resulted in the
      recombinant plasmid pMW75. Subsequent subcloning resulted in a 4.05 kb fragment
      contained in pLW14. One region of homology was observed upon hybridization to
      EcoR1 digested soybean DNA. Homologous sequences were also observed in Triticum
      DNA.Meso-diaminopimelate dehydrogenase activity was demonstrated inGlycine max
      embryos. Maximum enzymatic activity of the cloned enzyme was observed at a pH of
      8.0. The enzyme encoded by the soybean gene has an apparent molecular weight of
      67 000. 

PMID- 24310836
TI  - Characterization of developing oat seed mRNA: evidence for many globulin mRNAs.
AB  - Polyadenylated mRNA from developing oat (Avena sativa L.) seeds was isolated and
      analyzed. Prominent mRNA species of 18S, 15S and 12S were observed; the 18S mRNA
      was judged to be esentially free of ribosomal RNA by hybridization analysis. Size
      fractionation andin vitro translation of this mRNA was performed. SDS, IEF-SDS
      gel electrophoresis and immunoprecipitation were used to analyze the translation
      products. It is shown that globulin mRNA (18S) accounts for roughly 30% of the
      total mRNA in developing seeds, the 12S and 15S mRNAs accounting for the
      remainder. The 18S mRNA directs the synthesis of a series of distinct but related
      polypeptides, suggesting that some of the heterogeneity seen in the oat globulins
      is at the amino acid sequence level. 

PMID- 24310837
TI  - Evidence for translational control of storage protein biosynthesis during
      embryogenesis ofAvena sativa L. (oat endosperm).
AB  - Oat polysomes direct the synthesisin vitro of a large number of products, the
      majority of which are the salt-soluble globulins (1,3,10,11,21). Total RNA or
      poly A(+) RNA isolated from these polysomes directs the synthesis of the same
      number and types of products; however, the amount of globulins synthesized no
      longer represents the major products; rather, there is a decreased level of
      globulins and an increased amount of the other products synthesizedin vitro (6,
      18). These results imply that the translational control can dictate final product
      levels. Reconstruction experiments using oat poly A(+) mRNA and polysomal factors
      that are made free of endogenous RNA by nuclease digestion demonstrate that these
      factors do influence the translational specificity of oat globulin mRNA relative
      to other mRNAs. It is suggested that translational control is partially
      responsible for the levels of globulin in the mature grain. 

PMID- 24310838
TI  - Repeated sequences on mitochondrial DNA ofSpirodela oligorhiza.
AB  - Mitochondrial DNA ofSpirodela oligorhiza (duck weed) was analyzed with
      restriction enzymes. The genome size appears to be at least 250 kbp. Four
      different PstI fragments were cloned. These four clones contain a sequence which
      is reiterated about 100-fold on theSpirodela mitochondrial DNA. Hybridization
      analysis showed that a similar sequence is present onZea mays mitochondrial DNA,
      although much less reiterated here. The presence of these reiterated sequences
      might contribute to the physical heterogeneity of plant mitochondrial DNA. 

PMID- 24310839
TI  - Sequence of histidyl tRNA, present as a chloroplast insert in mtDNA ofZea mays.
AB  - Unfractionated tRNA, isolated from maize mitochondria, has been specifically
      labeled at the -CCA end and used to recover a tRNA gene-bearing fragment from a
      clone bank of maize mitochondrial DNA. This gene has been mapped, sequenced and
      found to carry the anticodon for histidine. The sequence of the gene and that of
      bases in its near vicinity are identical to maize chloroplast tRNA(His), although
      sequences more distant on the fragment are not homologous with cpDNA. The
      junction of the cpDNA insert has been sequenced. 

PMID- 24310840
TI  - Quantitative variation in components of the maize mitochondrial genome between
      tissues and between plants with different male-sterile cytoplasms.
AB  - The amounts of a 1.9 kb mitochondrial plasmid relative to sequences in another
      mitochondrial DNA replicon and also to nuclear ribosomal DNA sequences have been
      compared in maize leaves and anthers. Similar comparisons have been made between
      plants with the same nuclear genotype but containing normal, S, or T cytoplasms.
      The ratio of 1.9 kb plasmid to nuclear rDNA is lower in plants with normal
      cytoplasm than in plants with S or T cytoplasm. It also differs between leaves
      and anthers. Furthermore, the relative concentration of the mitochondrial DNA
      sequences belonging to different replicons differs between leaves and anthers. It
      is concluded that components of different mitochondrial replicons are not
      maintained in fixed ratios during development and that the concentration of the
      1.9 kb plasmid is regulated, in part, by cytoplasmically-inherited determinants.
      The 1.9 kb plasmid is absent from lines with the Vg cytoplasm, but related
      sequences are found in the maize nuclear genome. 

PMID- 24310841
TI  - Molecular cloning of a pea mRNA encoding an early light induced, nuclear coded
      chloroplast protein.
AB  - cDNA clones were isolated for a chloroplast protein, the mRNA of which is induced
      to maximum levels within 2-4 h after onset of illumination in five day old,
      etiolated pea seedlings.The cDNA library was constructed from poly(A)(+)-mRNA
      which was isolated from 4 h illuminated seedlings. The extremely short induction
      period of the early light induced protein(ELIP)-mRNA established the basis of our
      screening procedure. Colony hybridization experiments were performed with(32)P
      labelled cDNA probes, synthesized from RNA of seedlings which had been exposed to
      different programs of illumination. Plasmid DNAs were isolated from colonies
      showing strong hybridization signals exclusively with cDNA corresponding to the 4
      h-mRNA. Hybrid released translation of preselected plasmids p 17/C2 and p17/C4
      revealed a peptide of Mr 24 000. After posttranslational importin vitro, the
      processed product of Mr 17 000 appears in the chloroplast. Using these clones,
      the expression of the ELIP-mRNA was investigated by DOT-hybridization. The ELIP
      mRNA reaches maximum levels within 2-4 hours after onset of illumination. Our
      results correspond precisely to thein vivo characteristics and indicate positive
      identification of the sought clones. 

PMID- 24310842
TI  - Molecular analysis of mitochondria from a fertility restorer line of maize.
AB  - Inbred line Ky21 carries nuclear genes which restore fertility to all three
      cytoplasmic male sterile (cms) types of maize: T, C and S. By substituting the
      Ky21 cytoplasm into a nuclear background lacking all of the nuclear restorer
      genes, we have demonstrated that Ky21 contains a fertile (normal) cytoplasm. Gel
      electrophoresis of mitochondrial DNA from Ky21 demonstrated an approximately 2.1
      kb plasmid and no evidence for a 2.35 kb plasmid found in many normal cytoplasms
      of North American lines of maize. A 2.1 kb plasmid had been reported to be
      diagnostic for the T-type cms. However, the restriction endonuclease digestion
      pattern of Ky21 mtDNA more closely resembled that of normal lines than T-cms.
      Furthermore, mitochondria of Ky21 plants did not synthesize a 13 kilodalton
      polypeptide, which has only been found to be synthesized by T-type mitochondria.
      From these molecular criteria, as well as from the genetic analysis, we conclude
      that the mitochondria of the Ky21 universal restorer line are normal. In having a
      shorter form of a linear mtDNA plasmid, Ky21 resembles cytoplasms found in
      Mexican races of maize. 

PMID- 24310843
TI  - Site-specific mutagenesis in the TR-DNA region of octopine-type Ti plasmids.
AB  - Site-specific insertion and deletion mutations affecting all six of the
      eukaryotic-like genes in the TR-DNA region of the octopine-type Ti plasmids
      pTil5955 or pTiA6 have been generated. None of the mutations affected virulence
      or tumor morphology on sunflower. Mutations in the coding regions of two of the
      genes resulted in tumors without any detectable mannopine, mannopinic acid or
      agropine, and mutations in either the coding region or in the 3' untranslated
      region of a third gene eliminated biosynthesis of agropine, but not mannopine or
      mannopinic acid. Detection of two previously unobserved silver nitrate-positive
      substance in tumors incited by one of the mutant strains, together with data on
      the presence of opines in tumors incited by coinoculation with mixtures of
      different mutant strains, allowed us to propose the functional order of all three
      genes involved in the biosynthesis of mannopine, mannopinic acid and agropine. TR
      DNA was absent in tumors incited by anAgrobacterium tumefaciens strain harboring
      a Ti plasmid in which the right border of the TR-DNA region was deleted. 

PMID- 24310844
TI  - Conditional statistical inference with multistage testing designs.
AB  - In this paper it is demonstrated how statistical inference from multistage test
      designs can be made based on the conditional likelihood. Special attention is
      given to parameter estimation, as well as the evaluation of model fit. Two
      reasons are provided why the fit of simple measurement models is expected to be
      better in adaptive designs, compared to linear designs: more parameters are
      available for the same number of observations; and undesirable response behavior,
      like slipping and guessing, might be avoided owing to a better match between item
      difficulty and examinee proficiency. The results are illustrated with simulated
      data, as well as with real data. 

PMID- 24310845
TI  - A priori reliability of tests with cut score.
AB  - The theoretical probability of misclassification in a mastery test is exactly
      computed using the raw score probability distribution (in the Rasch model) as a
      function of the examinee's latent ability. The resulting misclassification
      probability curve, together with the latent ability distribution in the group of
      examinees, completely determines the expected rate of classification errors. It
      is shown that several distinct ability thresholds, playing different roles in
      connection to classification reliability, can be associated to a test with a
      single cut score. In particular, it is possible to define (and compute) two
      relevant ability intervals, which encapsulate the functioning of a mastery test
      (about and far from the cut score, respectively); the dependence of these
      intervals on the item difficulty spectrum is investigated. Extension to the 2PL
      model is also discussed, with emphasis on the effects of weighted scoring. 

PMID- 24310846
TI  - Substituent effects in cation-pi interactions revisited: a general approach based
      on intrinsic properties of the arenes.
AB  - The controversial proposal that substituent effects in cation-pi interactions can
      be attributed mainly to electrostatic effects between the ion and local dipoles
      has been theoretically studied by analyzing 171 aromatics interacting with Na(+).
      Our results stress the importance of both electrostatic and pi-polarization
      effects to properly describe cation-pi interactions. 

PMID- 24310847
TI  - Triclosan/copolymer containing toothpastes for oral health.
AB  - BACKGROUND: Periodontal disease and dental caries are highly prevalent oral
      diseases that can lead to pain and discomfort, oral hygiene and aesthetic
      problems, and eventually tooth loss, all of which can be costly to treat and are
      a burden to healthcare systems. Triclosan is an antibacterial agent with low
      toxicity, which, along with a copolymer for aiding retention, can be added to
      toothpastes to reduce plaque and gingivitis (inflammation of the gums). It is
      important that these additional ingredients do not interfere with the anticaries
      effect of the fluoride present in toothpastes, and that they are safe.
      OBJECTIVES: To assess the effects of triclosan/copolymer containing fluoride
      toothpastes, compared with fluoride toothpastes, for the long-term control of
      caries, plaque and gingivitis in children and adults. SEARCH METHODS: We searched
      the Cochrane Oral Health Group's Trials Register (to 19 August 2013), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2013, Issue 7), MEDLINE via OVID (1946 to 19 August 2013), EMBASE via OVID (1980
      to 19 August 2013), and the US National Institutes of Health Trials Register
      (clinicaltrials.gov) (to 19 August 2013). We applied no restrictions regarding
      language or date of publication in the searches of the electronic databases.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the
      effects triclosan/copolymer containing toothpastes on oral health. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed the search
      results against the inclusion criteria for this review, extracted data and
      carried out risk of bias assessments. We attempted to contact study authors for
      missing information or clarification when feasible. We combined sufficiently
      similar studies in meta-analyses using random-effects models when there were at
      least four studies (fixed-effect models when fewer than four studies), reporting
      mean differences (MD) for continuous data and risk ratios (RR) for dichotomous
      data. MAIN RESULTS: We included 30 studies, analysing 14,835 participants, in
      this review. We assessed 10 studies (33%) as at low risk of bias, nine (30%) as
      at high risk of bias and 11 (37%) as unclear. Plaque Compared with control, after
      six to seven months of use, triclosan/copolymer toothpaste reduced plaque by 0.47
      on a 0 to 5 scale (MD -0.47, 95% confidence interval (CI) -0.60 to -0.34, 20
      studies, 2675 participants, moderate-quality evidence). The control group mean
      was 2.17, representing a 22% reduction in plaque. After six to seven months of
      use, it also reduced the proportion of sites scoring 3 to 5 on a 0 to 5 scale by
      0.15 (MD -0.15, 95% CI -0.20 to -0.10, 13 studies, 1850 participants, moderate
      quality evidence). The control group mean was 0.37, representing a 41% reduction
      in plaque severity. Gingivitis After six to nine months of use,
      triclosan/copolymer toothpaste reduced inflammation by 0.27 on a 0 to 3 scale (MD
      -0.27, 95% CI -0.33 to -0.21, 20 studies, 2743 participants, moderate-quality
      evidence). The control group mean was 1.22, representing a 22% reduction in
      inflammation. After six to seven months of use, it reduced the proportion of
      bleeding sites (i.e. scoring 2 or 3 on the 0 to 3 scale) by 0.13 (MD -0.13, 95%
      CI -0.17 to -0.08, 15 studies, 1998 participants, moderate-quality evidence). The
      control group mean was 0.27, representing a 48% reduction in bleeding.
      Periodontitis After 36 months of use, there was no evidence of a difference
      between triclosan/copolymer toothpaste and control in the development of
      periodontitis (attachment loss) (RR 0.92, 95% CI 0.67 to 1.27, one study, 480
      participants, low-quality evidence). Caries After 24 to 36 months of use,
      triclosan/copolymer toothpaste slightly reduced coronal caries when using the
      decayed and filled surfaces (DFS) index (MD -0.16, 95% CI -0.31 to -0.02, four
      studies, 9692 participants, high-quality evidence). The control group mean was
      3.44, representing a 5% reduction in coronal caries. After 36 months of use,
      triclosan/copolymer toothpaste probably reduced root caries (MD -0.31, 95% CI 
      0.39 to -0.23, one study, 1357 participants, moderate-quality evidence). Calculus
      After six months of use, triclosan/copolymer toothpaste may have reduced the mean
      total calculus per participant by 2.12 mm (MD -2.12 mm, 95% CI -3.39 to -0.84,
      two studies, 415 participants, low-quality evidence). The control group mean was
      14.61 mm, representing a 15% reduction in calculus. Adverse effects There were no
      data available for meta-analysis regarding adverse effects, but 22 studies (73%)
      reported that there were no adverse effects caused by either the experimental or
      control toothpaste.There was considerable heterogeneity present in the meta
      analyses for plaque, gingivitis and calculus. Plaque and gingivitis showed such
      consistent results that it did not affect our conclusions, but the reader may
      wish to interpret the results with more caution. AUTHORS' CONCLUSIONS: There was
      moderate-quality evidence showing that toothpastes containing
      triclosan/copolymer, in addition to fluoride, reduced plaque, gingival
      inflammation and gingival bleeding when compared with fluoride toothpastes
      without triclosan/copolymer. These reductions may or may not be clinically
      important, and are evident regardless of initial plaque and gingivitis levels, or
      whether a baseline oral prophylaxis had taken place or not. High-quality evidence
      showed that triclosan/copolymer toothpastes lead to a small reduction in coronal
      caries. There was weaker evidence to show that triclosan/copolymer toothpastes
      may have reduced root caries and calculus, but insufficient evidence to show
      whether or not they prevented periodontitis. There do not appear to be any
      serious safety concerns regarding the use of triclosan/copolymer toothpastes in
      studies up to three years in duration.

PMID- 24310848
TI  - The case for de-escalation in antimicrobial therapy: time to change our strategy
      in the management of septic shock?

PMID- 24310849
TI  - Microbiological findings and adequacy of antibiotic treatment in the critically
      ill patient with drowning-associated pneumonia.

PMID- 24310851
TI  - Multilayered molecular profiling supported the monoclonal origin of metastatic
      renal cell carcinoma.
AB  - Primary renal cell carcinomas (pRCCs) have a high degree of intratumoral
      heterogeneity and are composed of multiple distinct subclones. However, it
      remains largely unknown that whether metastatic renal cell carcinomas (mRCCs)
      also have startling intratumoral heterogeneity or whether development of mRCCs is
      due to early dissemination or late diagnosis. To decipher the evolution of mRCC,
      we analyzed the multilayered molecular profiles of pRCC, local invasion of the
      vena cava (IVC), and distant metastasis to the brain (MB) from the same patient
      using whole-genome sequencing, whole-exome sequencing, DNA methylome profiling,
      and transcriptome sequencing. We found that mRCC had a lower degree of
      heterogeneity than pRCC and was likely to result from recent clonal expansion of
      a rare, advantageous subclone. Consequently, some key pathways that are targeted
      by clinically available drugs showed distinct expression patterns between pRCC
      and mRCC. From the genetic distances between different tumor subclones, we
      estimated that the progeny subclone giving rise to distant metastasis took over
      half a decade to acquire the full potential of metastasis since the birth of the
      subclone that evolved into IVC. Our evidence supported that mRCC was monoclonal
      and distant metastasis occurred late during renal cancer progression. Thus, there
      was a broad window for early detection of circulating tumor cells and future
      targeted treatments for patients with mRCCs should rely on the molecular profiles
      of metastases. 

PMID- 24310852
TI  - Treatment of life-threatening hypercapnia with isoflurane in an infant with
      status asthmaticus.
AB  - We encountered a 2-year-old child with life-threatening hypercapnia, with a
      PaCO(2) of 238 mm Hg and severe respiratory and metabolic acidosis, due to status
      asthmaticus that was refractory to steroid and bronchodilator therapy. Suspecting
      ventilatory failure and excessive ventilation-induced obstructive shock, we
      started respiratory physiotherapy in synchrony with her respiration, to
      facilitate exhalation from her over-inflated lungs. Isoflurane inhalation was
      commenced in preparation for extracorporeal circulation, to reduce the
      hypercapnia. The combination of respiratory physiotherapy and isoflurane
      inhalation resulted in a rapid decrease in ventilatory resistance and PaCO(2)
      levels within a few minutes, with recovery of consciousness within 60 min.
      Isoflurane inhalation was gradually discontinued and steroid and aminophylline
      therapy were commenced. The patient recovered completely without any recurrence
      of her bronchospasm and without any residual neurological deficits. In our
      patient with a severe asthmatic attack, decreased exhalation secondary to asthma
      and overventilation during artificial ventilation resulted in overinflation of
      the lungs, which in turn led to cerebral edema and obstructive cardiac failure.
      The favorable outcome in this case was due to the short duration of hypercapnia.
      Hence, we conclude that the duration of hypercapnia is an important determinant
      of the morbidity and mortality of status asthmaticus-induced severe hypercapnia.

PMID- 24310853
TI  - Ultrasound-guided sciatic nerve block: a comparison between four different
      infragluteal probe and needle alignment approaches.
AB  - PURPOSE: Our aim was compare onset time of sciatic nerve blockade (SNB) performed
      distal to the subgluteal fold using four different ultrasound (US)-guided
      approaches in patients undergoing foot or ankle surgery. METHODS: Patients were
      assigned to one of four groups: SI patients received SNB using short-axis (SA)
      view of the SN and in-plane (IP) placement of block needle (SA-IP approach); LI
      patients received SNB using long-axis (LA) view of the SN and IP needle placement
      (LA-IP approach); SO patients received the block using SA view of the SN and out
      of-plane (OP) needle placement (SA-OP approach); LO patients received SNB using
      LA view of the SN and OP needle placement (LA-OP). Primary outcome included onset
      time of sensory and motor SNB. Patient satisfaction concerning the postoperative
      analgesia was noted. RESULTS: The LI group had significantly faster onset of
      sensory blockade on the distribution of tibial nerve (16.0 +/- 5.6 vs. 23.5 +/-
      3.6) and common peroneal nerve (12.5 +/- 4.3 vs. 19.1 +/- 5.4 min) in comparison
      with the LO group. The LI group had significantly faster onset of motor blockade
      on the distribution of tibial nerve (21.1 +/- 6.2 vs. 26 +/- 3.1) and common
      peroneal nerve (17.7 +/- 4.8 vs. 23.7 +/- 5.8 min.) in comparison with the LO
      group. The LI group had the highest rate of patient satisfaction for
      postoperative analgesia and the LO group had the lowest. CONCLUSION: The LA-IP
      approach resulted in a rapid onset of SNB and was associated with the best
      satisfaction for postoperative analgesia in comparison with LA-OP, SA-IP, and SA
      OP approaches for patients undergoing foot and ankle surgery.

PMID- 24310854
TI  - Magnetoactive sponges for dynamic control of microfluidic flow patterns in
      microphysiological systems.
AB  - We developed a microfluidic flow-control system capable of dynamically generating
      various flow patterns on demand. The flow-control system is based on novel
      magnetoactive sponges embedded in microfluidic flow channels. Applying a non
      uniform magnetic field compresses the magnetoactive sponge, significantly
      reducing porosity and hydraulic conductivity. Tuning the applied magnetic field
      can dynamically vary the flow rate in the microfluidic channel. Pulsatile and
      physiological flow patterns with frequency between 1 and 3 Hz, flow rates between
      0.5 and 10 MUL min(-1) and duration over 3 weeks have been achieved. Smooth
      muscle cells in engineered blood vessels perfused for 7 days aligned
      perpendicular to the flow direction under pulsatile but not steady flow, similar
      to the in vivo orientation. Owing to its various advantages over traditional flow
      control methods, the new system potentially has important applications in
      microfluidic-based microphysiological systems to simulate the physiological
      nature of blood flow. 

PMID- 24310855
TI  - Rituximab for relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: This is an update of the Cochrane review "Rituximab for relapsing
      remitting multiple sclerosis" (first published in The Cochrane Library 2011,
      Issue 12).More than 80% of individuals with multiple sclerosis (MS) experience a
      relapsing-remitting disease course. Approximately 10 years after disease onset,
      an estimated 50% of individuals with relapsing-remitting MS (RRMS) convert to
      secondary progressive MS. MS causes a major socioeconomic burden for the
      individual patient and for society. Effective treatment that reduces relapse
      frequency and prevents progression could impact both costs and quality of life
      and help to reduce the socioeconomic burden of MS. Alternative and more effective
      MS treatments with new modes of action and good safety are needed to expand the
      current treatment repertoire. It has been shown that B lymphocytes are involved
      in the pathophysiology of MS and rituximab lyses B-cells via complement-dependent
      cytotoxicity and antibody-dependent cellular cytotoxicity. Current clinical
      trials are evaluating the role of rituximab as a B-cell depletion therapy in the
      treatment of RRMS. OBJECTIVES: The safety and effectiveness of rituximab, as
      monotherapy or combination therapy, versus placebo or approved disease-modifying
      drugs (DMDs) (interferon-beta (IFN-beta), glatiramer acetate, natalizumab,
      mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab) to
      reduce disease activity for people with RRMS were assessed. SEARCH METHODS: The
      Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare
      Diseases of the Central Nervous System Group Specialised Register (9 August
      2013). We checked the references in identified trials and manually searched the
      reports (2004 to August 2013) from neurological associations and MS societies in
      Europe and America. We also communicated with researchers who were participating
      in trials on rituximab and contacted Genentech, BiogenIdec and Roche. SELECTION
      CRITERIA: All randomised, double-blind, controlled parallel group clinical trials
      with a length of follow-up equal to or greater than one year evaluating
      rituximab, as monotherapy or combination therapy, versus placebo or approved DMDs
      for patients with RRMS without restrictions regarding dosage, administration
      frequency and duration of treatment. DATA COLLECTION AND ANALYSIS: We used the
      standard methodological procedures of The Cochrane Collaboration. Two review
      authors independently assessed trial quality and extracted data. Disagreements
      were discussed and resolved by consensus among the review authors. Principal
      investigators of included studies were contacted for additional data or
      confirmation of data. MAIN RESULTS: One trial involving 104 adult RRMS patients
      with an entry score <= 5.0 on the Expanded Disability Status Scale (EDSS) and at
      least one relapse during the preceding year was included. This trial evaluated
      rituximab as monotherapy versus placebo, with a single course of 1000 mg
      intravenous rituximab (on day 1 and day 15). A significant attrition bias was
      found at week 48 (24.0%). Patients receiving rituximab had a significant
      reduction in total number of gadolinium-enhancing lesions at week 24 (mean number
      0.5 versus 5.5; relative reduction 91%) and in annualised rate of relapse at week
      24 (0.37 versus 0.84) but not at week 48 (0.37 versus 0.72). Disability
      progression was not included as an outcome in this trial. More patients in the
      rituximab group had adverse events within the 24 hours after the first infusion
      (78.3% versus 40.0%), such as chills, headache, nausea, pyrexia, pruritus,
      fatigue, throat irritation, pharyngolaryngeal pain, and most were mild-to
      moderate events (92.6%). The most common infection-associated adverse events (>
      10% in the rituximab group) were nasopharyngitis, upper respiratory tract
      infections, urinary tract infections and sinusitis. Among them, only urinary
      tract infections (14.5% versus 8.6%) and sinusitis (13.0% versus 8.6%) were more
      common in the rituximab group. One ongoing trial was identified. AUTHORS'
      CONCLUSIONS: There is not sufficient evidence to support the use of rituximab as
      a disease-modifying therapy for RRMS because only one RCT was included. The
      quality of the study was limited due to high attrition bias, the small number of
      participants, and short follow-up. The beneficial effects of rituximab for RRMS
      remain inconclusive. However, short-term treatment with a single course of
      rituximab was safe for most patients with RRMS. Mild-to-moderate infusion
      associated adverse events were common, as well as nasopharyngitis, upper
      respiratory tract infections, urinary tract infections and sinusitis. The
      potential benefits of rituximab for treating RRMS need to be evaluated in large
      scale studies that are of high quality along with long-term safety.

PMID- 24310856
TI  - Single molecule study of DNA collision with elliptical nanoposts conveyed by
      hydrodynamics.
AB  - Periodic arrays of micro- or nanopillars constitute solid-state matrices with
      excellent properties for DNA size separation. Nanofabrication technologies offer
      many solutions to tailor the geometry of obstacle arrays, yet most studies have
      been conducted with cylinders arranged in hexagonal lattices. In this report, we
      investigate the dynamics of single DNA collision with elliptical nanoposts using
      hydrodynamic actuation. Our data show that the asymmetry of the obstacles has
      minor effect on unhooking dynamics, and thus confirm recent predictions obtained
      by Brownian dynamics simulations. In addition, we show that the disengagement
      dynamics are correctly predicted by models of electrophoresis, and propose that
      this consistency is associated to the confinement in slit-like channels. We
      finally conclude that elliptical posts are expected to marginally improve the
      performances of separation devices. 

PMID- 24310857
TI  - Simultaneous determination of free and total glycerol in biodiesel by capillary
      electrophoresis using multiple short-end injection.
AB  - A rapid method for the simultaneous determination of free glycerol (FG) and total
      glycerol (TG) in biodiesel by CE using a short-end multiple injection (SE/MI)
      configuration system is described. The sample preparation for FG involves the
      extraction of glycerol with water and for TG a saponification reaction is carried
      out followed by extraction as in the case of FG. The glycerol extracted in both
      cases is submitted to periodate oxidation and the iodate ions formed are measured
      on a CE-SE/MI system. The relevance of this study lies in the fact that no
      analytical procedure has been previously reported for the determination of TG (or
      of FG and TG simultaneously) by CE. The optimum conditions for the
      saponification/extraction process were 1.25% KOH and 25 degrees C, with a time of
      only 5 min, and biodiesel mass in the range of 50.0-200.0 mg can be used.
      Multiple injections were performed hydrodynamically with negative pressure as
      follows: 50 mbar/3s (FG sample); 50 mbar/6s (electrolyte spacer); 50 mbar/3s (TG
      sample). The linear range obtained was 1.55-46.5 mg/L with R(2) > 0.99. The LOD
      and LOQ were 0.16 mg/L and 0.47 mg/L, respectively for TG. The method provides
      acceptable throughput for application in quality control and monitoring biodiesel
      synthesis process. In addition, it offers simple sample preparation
      (saponification process), it can be applied to a variety biodiesel samples
      (soybean, castor, and waste cooking oils) and it can be used for the
      determination of two key parameters related to the biodiesel quality with a fast
      separation (less than 30 s) using an optimized CE-SE/MI system. 

PMID- 24310858
TI  - Development of a multiplex system to assess DNA persistence in taphonomic
      studies.
AB  - In this study, we have developed a PCR multiplex that can be used to assess DNA
      degradation and at the same time monitor for inhibition: primers have been
      designed to amplify human, pig, and rabbit DNA, allowing pig and rabbit to be
      used as experimental models for taphonomic research, but also enabling studies on
      human DNA persistence in forensic evidence. Internal amplified controls have been
      added to monitor for inhibition, allowing the effects of degradation and
      inhibition to be differentiated. Sequence data for single-copy nuclear
      recombination activation gene (RAG-1) from human, pig, and rabbit were aligned to
      identify conserved regions and primers were designed that targeted amplicons of
      70, 194, 305, and 384 bp. Robust amplification in all three species was possible
      using as little as 0.3 ng of template DNA. These have been combined with primers
      that will amplify a bacterial DNA template within the PCR. The multiplex has been
      evaluated in a series of experiments to gain more knowledge of DNA persistence in
      soft tissues, which can be important when assessing what material to collect
      following events such as mass disasters or conflict, when muscle or bone material
      can be used to aid with the identification of human remains. The experiments used
      pigs as a model species. When whole pig bodies were exposed to the environment in
      Northwest England, DNA in muscle tissue persisted for over 24 days in the summer
      and over 77 days in the winter, with full profiles generated from these samples.
      In addition to time, accumulated degree days (ADD) were also used as a measure
      that combines both time and temperature-24 days was in summer equivalent to 295
      ADD whereas 77 days in winter was equivalent to 494 ADD. 

PMID- 24310859
TI  - Identification multiplex assay of 19 terrestrial mammal species present in New
      Zealand.
AB  - An identification assay has been developed that allows accurate detection of 19
      of the most common terrestrial mammals present in New Zealand (cow, red deer,
      goat, dog, horse, hedgehog, cat, tammar wallaby, mouse, weasel, ferret, stoat,
      sheep, rabbit, Pacific rat, Norway rat, ship rat, pig, and brushtail possum).
      This technique utilizes species-specific primers that, combined in a multiplex
      PCR, target small fragments of the mitochondrial cytochrome b gene. Each species,
      except hedgehog, produces two distinctive species-specific fragments, making the
      assay self-confirmatory and enabling the identification of multiple species
      simultaneously in DNA mixtures. The multiplex assay detects as little as 100
      copies of mitochondrial DNA, which makes it a very reliable tool for degraded and
      trace samples. Reliability, accuracy, reproducibility, and sensitivity tests to
      validate the technique were performed. The technique featured here enabled a
      prompt response in a predation specific event, but can also be useful for
      wildlife management and conservation, pest incursions detection, forensic, and
      industrial purposes in a very simple and cost-effective manner. 

PMID- 24310867
TI  - How to be a savior.

PMID- 24310865
TI  - Early airway structural changes in cystic fibrosis pigs as a determinant of
      particle distribution and deposition.
AB  - The pathogenesis of cystic fibrosis (CF) airway disease is not well understood. A
      porcine CF model was recently generated, and these animals develop lung disease
      similar to humans with CF. At birth, before infection and inflammation, CF pigs
      have airways that are irregularly shaped and have a reduced caliber compared to
      non-CF pigs. We hypothesized that these airway structural abnormalities affect
      airflow patterns and particle distribution. To test this hypothesis we used
      computational fluid dynamics (CFD) on airway geometries obtained by computed
      tomography of newborn non-CF and CF pigs. For the same flow rate, newborn CF pig
      airways exhibited higher air velocity and resistance compared to non-CF. Moreover
      we found that, at the carina bifurcation, particles greater than 5-MUm preferably
      distributed to the right CF lung despite almost equal airflow ventilation in non
      CF and CF. CFD modeling also predicted that deposition efficiency was greater in
      CF compared to non-CF for 5- and 10-MUm particles. These differences were most
      significant in the airways included in the geometry supplying the right caudal,
      right accessory, left caudal, and left cranial lobes. The irregular particle
      distribution and increased deposition in newborn CF pig airways suggest that
      early airway structural abnormalities might contribute to CF disease
      pathogenesis. 

PMID- 24310866
TI  - Decreased body mass index is associated with poor prognosis in patients with
      multiple myeloma.
AB  - Obesity increases morbidity in and mortality of patients with various types of
      cancer. However, the proportion of obese individuals in Asia is smaller than that
      in Western populations and only a few studies have explored the effect of obesity
      at the time of diagnosis on the survival of Asian patients with multiple myeloma
      (MM). Therefore, we investigated the relationship between body mass index (BMI)
      at diagnosis, and clinical manifestations, in MM patients. We also measured
      overall survival (OS) in terms of BMI groupings. Patients were subdivided into
      three groups based on hazard ratios (HRs) associated with BMIs of <20, 20-24.9,
      and >=25 kg/m(2). The median survival times were 25.5 months in patients with a
      BMI of <20 kg/m(2), 56.8 months for those with a BMI of 20-24.9 kg/m(2), and 76
      months in patients with a BMI of >=25 kg/m(2). Patients with a BMI of <20 kg/m(2)
      exhibited poorer performance status and a lower hemoglobin level at diagnosis
      than did others, and renal failure (serum creatinine >=2 mg/dl) was much more
      often observed in such patients than in those of other groups. Both univariate
      and multivariate analyses showed that BMI <20 kg/m(2) (HR 1.831, 95 % confidence
      interval [CI] 1.005-3.337; P = 0.048) and performance of autologous stem cell
      transplantation (HR 0.257, 95 % CI 0.139-0.475, P < 0.001) were significantly
      (negatively) associated with OS. In conclusion, a low BMI (<20 kg/m(2)) at the
      time of diagnosis was associated with poor survival of MM patients. 

PMID- 24310868
TI  - Soteriological dimensions in the work of Heinz Kohut.
AB  - A framework of theological inquiry is utilized to illuminate soteriological
      dimensions implicit in Heinz Kohut's psychology of the self as expressed in his
      most recent work,The Restoration of the Self. Kohut's new formulations involve
      the unfolding of a saving approach that through its broad application seeks to
      overcome "the psychological danger that puts the psychological survival of modern
      Western man into the greatest jeopardy." The theological inquiry employed asks:
      What is the essential nature of man? How has man fallen away from his essential
      self? By what means is he to be saved from his broken condition? Kohut's implicit
      and explicit "answers" are summarized by dealing with four cardinal issues in his
      book: definitions of the self: the relationship of a psychology of the self to
      other psychologies; theory concerning the selfs structure, development, and
      restoration; and the centrality of the empathic response. 

PMID- 24310869
TI  - Humanistic psychology and religion: Steps toward reconciliation.
AB  - Disagreements have surfaced recently among rank- and-file mental health
      practitioners regarding the relationship between psychology and religion. To
      mediate these differences and misunderstandings, a study is presented here of the
      basic concepts of humanistic psychology vis-a-vis major elements of Judeo
      Christian biblical theology. An assumption is posited that all forms of knowledge
      share a fundamental language basis and symbolic system regarding the ultimate
      questions and meanings of existence. From this presupposition similarities and
      congruities among specific elements of humanistic psychology and biblical
      theology are discussed, providing a basis for more intensive empathic dialogue
      and cooperative research. A bridge is established to enable therapists to
      understand better their clients' religious conflicts and/or emotional stresses
      caused by religious factors. 

PMID- 24310870
TI  - Wifely submission: Psychological/spiritual growth perspectives.
AB  - Wifely submission is reviewed from a perspective of psychological and spiritual
      health with regard to sociocultural arguments, pathological personal motives, and
      growth motives for submission. Four sociocultural arguments for wifely submission
      are discussed: social order, sociobiological opinions, maintenance of sexual
      differences, and scriptural authority. Pathological personal motives for
      submission assessed are security seeking, masochistic submission, neurotic love
      seeking, and manipulation. Growth bases considered are service to the partner,
      marital mutuality, overcoming personal faults, and vowed commitment to the
      spiritual life. Implications for marriage and premarital counseling are drawn. 

PMID- 24310871
TI  - King ego and the double-sex dancer.
AB  - The god representative of the energy of life in ancient Greece was Dionysos. As
      such, he was bisexual, for life in its wholeness contains all the individual
      forms it generates. The emphasis upon androgyny and sexual fusion in his cult
      results from man's effort to realize the wholeness of that life of which he is
      merely a fragment. The achievement of that fullness, life's experience of itself,
      is ecstasy; suffering, on the other hand, is fundamentally life's alienation from
      itself. In the myths and rituals of Dionysos we witness the dialectic of
      affirmation and denial of the life force. 

PMID- 24310872
TI  - Near-death experience: A review from pastoral psychology.
AB  - Published interpretations of near-death experience from the vantage of pastoral
      psychology are virtually nonexistent. Subjective reports from survivors and
      investigative contributions from other disciplines are scattered and diverse. A
      comparison of twenty-one near-death experience transcendence accounts with the
      available literature may not only offer direction for further systematic inquiry
      but also contribute to our pastoral understanding of life and death. 

PMID- 24310873
TI  - A way out of the wasteland.
AB  - This essay describes the author's experiences with Judaism, with the art of Jane
      Austen, and with the thought of a radical Catholic theologian, Leslie Dewart. The
      author's synthesis of these disparate elements indicates that it is possible to
      achieve a religious view that satisfies one's spiritual and emotional needs
      without conflicting with the widespread modern conception of the integrity and
      openness of man's evolution. 

PMID- 24310874
TI  - A fact-finder's journey to Europe.
AB  - The author undertook a trip to sixteen cities in eight European countries to
      study Continental models of integrating spiritual development and mental health
      and to look at training programs in pastoral counseling. He found a growing
      secularization of clergy who want to offer human services and cannot do so within
      established church hierarchies. In Roman Catholic areas he found pastoral
      counseling services directed to the religious professional rather than to the
      laity or the public. Training programs have yet to be fully developed. Only the
      Swedish model, in its history and multidisciplinary character, resembles the
      situation in the United States. 

PMID- 24310875
TI  - Activated Nrf2 impairs liver regeneration in mice by activation of genes involved
      in cell-cycle control and apoptosis.
AB  - The nuclear factor erythroid-derived 2, like 2 (Nrf2) transcription factor is a
      key regulator of the antioxidant defense system, and pharmacological activation
      of Nrf2 is a promising strategy for prevention of toxin-induced liver damage.
      However, the consequences of Nrf2 activation on liver regeneration (LR) have not
      been determined. To address this question, we generated mice expressing a
      constitutively active Nrf2 (caNrf2) mutant in hepatocytes. Expression of the
      transgene did not affect liver homeostasis. Surprisingly, however, there was no
      beneficial effect of Nrf2 activation on CCl4 -induced liver injury and fibrosis.
      Most important, LR after partial hepatectomy was impaired in caNrf2-transgenic
      mice as a result of delayed hepatocyte proliferation and enhanced apoptosis of
      these cells after liver injury. Mechanistically, this involved up-regulation of
      the cyclin-dependent kinase inhibitor p15 and the proapoptotic protein Bcl2l11
      (Bim). Using chromatin immunoprecipitation, we show that the p15 and Bcl2l11
      genes are direct targets of Nrf2, which are activated under hyperproliferative
      conditions in the liver. CONCLUSION: Activated Nrf2 delays proliferation and
      induces apoptosis of hepatocytes in the regenerating liver. These negative
      effects of Nrf2 activation on LR should be considered when Nrf2-activating
      compounds are used for prevention of liver damage.

PMID- 24310876
TI  - Nuclear and mitochondrial DNA have sequence homology with a chloroplast gene.
AB  - A PstI 7.7 kbp fragment from chloroplast (ct) DNA of spinach shows homology to an
      EcoRI 8.3 kbp fragment of mitochondrial (mt) DNA and in turn, both are homologous
      to a number of common regions of nuclear (n) DNA. The common area of homology
      between the chloroplast and mitochondrial fragments is between a KpnI 1.8 segment
      internal to the PstI sites in the ctDNA and an EcoRI/BamHI 2.9 kbp fragment at
      one end of the mitochondrial 8.3 kbp fragment. The KpnI 1.8 kbp ctDNA fragment is
      within a structural gene for the P700 chlorophyll a apoprotein. Further analysis
      of this KpnI 1.8 kbp fragment confined the homologous region in mtDNA to a ct 0.8
      kbp HpaII fragment. These smaller pieces of the organellar genomes share
      homologies with nuclear DNA as well as displaying unique hybridization sites. The
      observations reported here demonstrate that there is a common or closely related
      sequence in all three genetic compartments of the cell. 

PMID- 24310877
TI  - Patterns of post-infectional protein synthesis in barley carrying different genes
      for resistance to the powdery mildew fungus.
AB  - Pairs of susceptible and resistant, near-isogenic cultivars ofHordeum vulgare
      which differ for the Mla, Mlk and Mlp genes for resistance toErysiphe graminis f.
      sp.hordei were inoculated with race 3 of this pathogen and patterns of protein
      synthesis associated with primary infection mapped using pulse-labelling with L
      [(35)S]methionine and 2-dimensional electrophoresis. Extraction of proteins with
      buffer containing detergent revealed the enhanced synthesis of 5 and 8
      polypeptides at 25 and 30 h respectively after inoculation of barley carrying the
      Mla gene (cvMla). The enhanced synthesis of these same polypeptides together with
      11 additional polypeptides was observed at 48 h and 72 h after inoculation of
      barley carrying either the Mlp (cvMlp) or Mlk (cvMlk) genes. The labelling of
      several major constitutive polypeptides was suppressed in cvMla at 24 h after
      inoculation; the labelling of six of these polypeptides was also suppressed in
      both cvMlp and cvMlk but not until 48 and 72 h after inoculation. These results
      indicate that changes occur in the synthesis of some common polypeptides
      following infection of cultivars carrying different resistance genes but the
      timing and extent of these changes varies with the resistance gene in the host. 

PMID- 24310878
TI  - The detection of leghemoglobin-line sequences in legumes and non-legumes.
AB  - Leghemoglobin is a major component of the nitrogen-fixing nodules formed by
      legumes in association with bacterial symbionts of the genusRhizobium. It is
      thought to be involved in regulating the oxygen tension within nodules. In a
      series of Southern blot experiments using cloned soybean leghemoglobin cDNAs as
      hybridization probes, cross-hybridizing sequences have been detected in legumes
      closely related to soybean (members of the Leguminosae subfamily Papilionoideae),
      as well as in a distantly related legume not reported to be nodulated (subfamily
      Caesalpinioideae). With the same probes, the presence of cross-hybridizing
      sequences has also been detected in plants outside the Leguminosae, including two
      nitrogen-fixing non-legumes and one species which is not nodulated. These results
      suggest that the genes for oxygen-binding proteins may be more widely dispersed
      than previously thought. 

PMID- 24310879
TI  - Comparison of multimeric plus and minus forms of viroids and virusoids.
AB  - In order to investigate the mechanism of replication of viroids and virusoids, we
      have compared the replication intermediates of three members of each group in
      nucleic acid extracts of infected plants. Viroids were avocado sunblotch viroid
      (ASBV), citrus exocortis viroid (CEV) and coconut cadang cadang viroid (CCCV).
      Virusoids were from velvet tobacco mottle virus (VTMoV), solanum nodiflorum
      mottle virus (SNMV) and lucerne transient streak virus (LTSV). Analysis of
      intermediates was by the Northern hybridization technique with single-strand DNA
      and RNA probes prepared from recombinant DNA clones. The results obtained are
      discussed in terms of current models of viroid and virusoid replication.The plus
      RNA species consisted of an oligomeric series up to decamers based on the unit of
      full-length viroid or virusoid, which was always the major component, except for
      CEV where only monomer and dimer species were found. In the case of ASBV and the
      virusoids of VTMoV and SNMV, a minor, multimeric series of components (X-bands)
      was superimposed on the main oligomeric series.The complementary minus species
      proved more difficult to detect and characterise, with each viroid and virusoid
      exhibiting a unique pattern on Northern hybridization. However, they all had
      greater than unit-length minus species. In addition, minus species analogous to
      the plus X-bands were found in ASBV and CEV. The experimental difficulties
      encountered in this work are discussed in terms of the problem of detecting minus
      species by Northern analysis in the presence of excess complementary plus
      species. 

PMID- 24310880
TI  - Localization and nucleotide sequences of the tRNA GCC (Gly) , tRNA GUC (Asp) and
      tRNA GCA (Cys) genes from wheat chloroplast.
AB  - The location on the wheat chloroplast DNA map and the nucleotide sequences of the
      genes coding for tRNA GCC (Gly) (trnG-GCC), tRNA GUC (Asp) (trnD-GUC) and tRNA
      GCA (Cys) (trnC-GCA) have been determined. These three genes are located in the
      large single copy region of the chloroplast genome, about half-way between one of
      the inverted repeats and the gene for the alpha subunit of ATP synthase. They are
      located on two Bam H1 fragments, called B6 and B18 by Bowmanet al. (1), which are
      separated by about 450 bp and which were cloned in our laboratory to allow
      sequencing. ThetrnD-GUC andtrnC-GCA sequences show 98.6 and 89% homology,
      respectively, with the corresponding spinach chloroplast tRNA genes sequences
      (2), which are the only other higher plant chloroplasttrnD-GUC andtrnC-GCA
      sequenced so far, while no othertrnG-GCC sequence has been published. ThetrnG-GCC
      sequence shows only 58% homology with the corresponding gene sequence inEuglena
      chloroplasts (3). 

PMID- 24310881
TI  - Plant DNA polymerases.

PMID- 24310882
TI  - Chloroplast transfer RNAs and tRNA genes of wheat.
AB  - Fractionation (by two-dimensional polyacrylamide gel electrophoresis) of total
      tRNA from wheat chloroplasts yields about 33 RNA spots. Of these, 30 have been
      identified by aminoacylation as containing tRNAs specific for 17 amino
      acids.Hybridization of labeled individual tRNAs to cloned chloroplast DNA
      fragments has revealed the location of at least nine pairs of tRNA genes in the
      segments of the inverted repeat, at least twelve tRNA genes in the large single
      copy region and one tRNA gene in the small single copy region.A comparison of
      this wheat chloroplast tRNA gene map to that of maize and of other higher plants
      suggests that gene rearrangements have occurred during evolution, even within
      cereal chloroplast DNA. These rearrangements have taken place within the inverted
      repeat, within the large single copy region and between the inverted repeat and
      the large single copy region. 

PMID- 24310884
TI  - Plant-virus-based vectors for gene transfer will be of limited use because of the
      high error frequency during viral RNA synthesis.
AB  - The error frequency during the RNA replication of alfalfa mosaic virus (AMV) was
      calculated to be significantly higher than 10(-5). It may be expected that RNA
      synthesis in general will have low fidelity compared to DNA synthesis. The low
      fidelity of RNA replication will severely restrict the usefulness of vectors for
      genetic engineering which are based on RNA viruses, viroids or DNA viruses which
      are replicated via an RNA intermediate (e.g. caulimoviruses). Spontaneous mutants
      selected by host shift were found to be much less stable than UV-induced mutants.
      This difference points to variations in fidelity during RNA synthesis, probably
      due to the local sequence of the template. 

PMID- 24310885
TI  - Plant-virus-based vectors for gene transfer may be of considerable use despite a
      presumed high error frequency during RNA synthesis.
AB  - The RNA genomes of some plant viruses have properties which make them suitable
      for development into vectors for gene transfer. It has been claimed that the low
      fidelity of RNA synthesizing enzymes may limit the usefulness of such vectors.
      Arguments are presented here to indicate that the problem may not be serious.
      Examples are presented of plant RNA replicons which carry relatively stable
      coding sequences whose products are superfluous to either the replicon or the
      host. In addition, there are numerous instances in which slowly replicating virus
      strains are maintained in 'pure' culture in a host and are not overgrown by more
      rapidly replicating strains. It is difficult to estimate the error frequency of
      RNA replicating enzymes. Methods which rely on host-shift may be subject to
      error. 

PMID- 24310886
TI  - Far-red mediated polyribosome formation in radish cotyledons : Effect of
      endogenous ribonucleases on polyribosome recovery.
AB  - The total ribosome content of radish cotyledons increases during the first 2-3
      days of germination both in darkness and under far-red light irradiation;
      ribonuclease activity is not under phytochrome control during this period.
      Changes in ribonuclease activity interfere with the analysis of the polyribosomal
      population. A maximal ratio of polysomes to monosomes is observed 12 h after the
      onset of far-red light and then it decreases. A 12 h far-red irradiation
      stimulates the in vivo incorporation of amino acids into proteins. This
      stimulation persists when seedlings are transferred for 4 h to the dark. 

PMID- 24310887
TI  - Phytochrome-regulated transfer of fructosidase from cytoplasm to cell wall in
      Raphanus sativus L. hypocotyls.
AB  - The far-red absorbing form of phytochrome, Pfr, rapidly increases the rate of
      transfer of beta-fructosidase (E.C.3.2.1.26) from the cytoplasm to the cell wall
      in radish hypocotyls. Far-red light increases the level of enzyme in a
      particulate fraction: after two hours of light treatment, the particulate enzyme
      is associated almost exclusively with the endoplasmic reticulum. Transfer from
      the endoplasmic reticulum to the cell wall involves an incorporation into Golgi
      bodies and the plasmalemma: these membrane fractions were separated by
      centrifugation on a discontinuous sucrose density gradient and their degree of
      purity was determined by the use of known biochemical markers. With respect to
      beta-fructosidase, light controls, via Pfr: (1) the total amount, (2) the
      incorporation into the endoplasmic reticulum and (3) the transfer to the cell
      wall. These three processes have different sensitivities to cycloheximide. 

PMID- 24310888
TI  - The blockage in the G 1 phase of the cell cycle in the dormant shoot apex of ash.
AB  - The shoot apex of the terminal bud was studied in four successive physiological
      states: during dormancy, when dormancy breaks, during the third week after the
      break of dormancy, and during a later typical period of active growth. DNA
      content was measured in Feulgen-stained nuclei of the axial zone, of the lateral
      zone, and of the rib meristem. The mitotic index was established for each zone of
      the meristem. During the period of dormancy, all the nuclei of the meristem are
      in phase G 1 of the cell cycle and are blocked at the same point common to all
      nuclei. When dormancy breaks, this blockage is removed simultaneously and all
      nuclei in the shoot apex resume their cell cycles starting at the same point. The
      cycles remain synchronized for awhile. In the axial zone they remain synchronized
      until the third week after resumption of active growth. 

PMID- 24310889
TI  - Water permeability of plant cuticles: The effect of temperature on diffusion of
      water.
AB  - The effect of temperature on water permeability of plant cuticles (astomatous
      Citrus leaf cuticles) has been investigated. The Arrhenius plot (logarithm of the
      permeability coefficient vs. 1/temperature) has two linear portions that
      intersect at 44 degrees  C. Evidence is presented to show that this intersection
      represents the solid/liquid phase transition of cuticular lipids. As the
      Arrhenius plot has only one phase transition in the temperature range of 5 to 80
      degrees  C, it appears that all soluble cuticular lipids in the cuticle are
      present as a homogeneous mixture rather than as individual layers differing in
      composition. This view is supported by electron spin resonance evidence showing
      homogenous distribution of spin label fatty acids. The original distribution of
      soluble cuticular lipids is irreversibly altered by heating cuticular membranes
      above the transition temperature. This is accompanied by an irreversible increase
      in water peremeability, demonstrating the importance of the structure of
      cuticular lipids with regard to cuticular permeability. 

PMID- 24310890
TI  - Cytokinins and in vitro development of Phaseolus coccineus embryos.
AB  - Phaseolus coccineus embryos at the heartshaped and the middle cotyledonary stages
      were cultured in vitro on media added with different concentrations of zeatin (Z)
      or zeatin riboside (Zr). Growth of early embryos was clearly favored by
      concentrations of Z from 10(-8) M to 10(-5) M, lower concentrations having no
      effect. Zr also promoted in vitro growth of early embryos, but in concentrations
      from 10(-12) M to 10(-10) M, higher concentrations being inhibitory. More
      developed embryos were scarcely sensitive to the presence in the culture medium
      of either Z or Zr at any concentration. 

PMID- 24310891
TI  - The activity and malate inhibition/stimulation of phosphoenolpyruvate-carboxylase
      in crassulacean-acid-metabolism plants in their natural environment.
AB  - The effect of environmental conditions, temperature, relative humidity, and
      light, together with the regulation of PEPC (phosphoenolpyruvate-carboxylase)
      activity by malate and pH on CAM (crassulacean acid metabolism), was studied in
      members of the Mesembryanthemaceae in their natural environment, the southern
      Namib desert. It was found that during a 24 h period the characteristics of PEPC
      change. Before sunrise the activity is higher when measured at pH 7 than 8. With
      bright sunlight the activity measured at pH 7 drops to 20% of its pre-sunrise
      value, the activity only recovers gradually after malate disappearance and stays
      constant throughout the night. When measured at pH 8, PEPC shows an opposite
      behavior, i.e., activity increases in bright sunlight and declines as the pH 7
      activity increases. A day-night oscillation in the capacity of malate to
      stimulate or inhibit PEPC was found. During the day malate inhibits about 90% of
      the PEPC activity at both pH 7 and 8. After sunset there is a sudden decrease in
      this inhibition and, at pH 8, malate stimulates the activity by 50%. At pH 7 the
      stimulation was less.Both stomatal conductance and malate formation were found to
      increase only when the relative humidity at night rose to 80%. Changes in the
      properties of the PEPC coincided with the exposure to bright sunlight and changes
      in leaf temperature. The importance of these metabolic and environmental controls
      on the regulation of CAM in the Mesembryanthemaceae will be discussed. 

PMID- 24310892
TI  - Regulation of adenosine 5'-phosphosulfate sulfotransferase activity by H2S and
      cyst(e)ine in primary leaves of Phaseolus vulgaris L.
AB  - During chloroplast development in the primary leaves of Phaseolus vulgaris, the
      extractable activity of adenosine 5'-phosphosulfate sulfotransferase increased
      ten-fold. When chloroplast development took place in air enriched with 3.5 MUl
      H2S.l(-1) there was a decrease in adenosine 5'-phosphosulfate sulfotransferase
      activity. Cyst(e)ine in concentrations up to 1 mM (in the external medium) did
      not affect the increase in adenosine 5'-phosphosulfate sulfotransferase activity
      in intact plants. In plants with excised roots, 0.75 mM cyst(e)ine inhibited this
      increase. In green primary leaves, H2S or cyst(e)ine treatment resulted in a
      decrease of extractable adenosine 5'-phosphosulfate sulfotransferase activity. In
      intact plants, this effect of cyst(e)ine was observed at a concentration of 1 mM,
      and in plants with excised roots, 0.25 mM had a comparable effect.In developing
      plants, the extractable activities of O-acetyl-L-serine sulfhydrylase (EC
      4.2.99.9) and ribulosebisphosphate carboxylase (EC 4.1.1.39.) were not affected
      by H2S or cyst(e)ine. 

PMID- 24310893
TI  - Solute regulation and growth by roots and shoots of water-stressed maize plants.
AB  - Potted maize seedlings were subjected to a single period of water stress. As the
      severity of water stress increased, measurements were made of leaf and root
      solute and water potentials, leaf diffusive conductance and leaf and root growth.
      After day four of the drying cycle, the rate of leaf extension and the
      development of leaf area were reduced. This reduction correlated well with a
      reduction in leaf turgor which occurred at this time. A significant accumulation
      of solutes in the root tips of the unwatered plants resulted in the maintenance
      of root turgor for the duration of the water stress treatment. Root growth of the
      unwatered plants was also maintained as the severity of water stress increased. A
      mild degree of water stress resulted in a net increase in root growth compared to
      the situation in well-watered plants. The significance of solute regulation and
      continued root growth for plants growing in drying soil is discussed. 

PMID- 24310894
TI  - Concanavalin A binding to Chlamydomonas eugametos flagellar proteins and its
      effect on sexual reproduction.
AB  - The relative amounts of Concanavalin A (Con A) bound by gamete and vegetative
      flagella of both mating types (mt (+) and mt (-)) of Chlamydomonas eugametos were
      determined using (125)I-Con A. Con A agglutinated all cell types by cross-linking
      their flagella in a random manner. No correlation was found between the extent of
      Con A-binding and Con A-mediated isoagglutination. Con A inhibited the sexual
      interaction between gametes at various levels. In mt (+) gametes it blocked
      sexual agglutination, whereas in mt (-) gametes it prevented papillar fusion. By
      SDS-gel electrophoresis nine Con A-binding components were found to be present in
      flagella. However, it was not possible to allocate a role in sexual agglutination
      to any of these components since they were present in all cell types, including
      vegetative cells which are not able to sexually agglutinate. 

PMID- 24310895
TI  - Long-distance transport of sulfur in Nicotiana tabacum.
AB  - Sulfur reduction in tobacco plants is a light-enhanced process that predominantly
      takes place in the leaves rather than the roots. The amount of sulfate reduced in
      mature leaves can exceed their own requirement and enables an export of reduced
      sulfur, both basipetal toward the roots as well as acropetal toward the growing
      parts of the stem. Evidence is presented that translocation of reduced sulfur
      toward the roots occurs in the phloem. TLC and paper chromatography reveal that
      glutathione is the main transport form of reduced sulfur in tobacco plants; 67
      70% of reduced (35)S was confined to glutathione, 27-30% to methionine, and 2-8%
      to cysteine. 

PMID- 24310896
TI  - Activation, synthesis and turnover of nitrate reductase controlled by nitrate and
      ammonium in Chlorella vulgaris.
AB  - Rates of synthesis and turnover of nitrate reductase in Chlorella vulgaris have
      been estimated from density-labelling experiments. It is demonstrated that
      nitrate stimulates the rate of turnover of the enzyme. Upon transfer of Chlorella
      from ammonium to nitrate medium there is a rapid increase in nitrate reductase
      activity, only part of which is a consequence of increased de novo synthesis:
      there must also be considerable activation of existing enzyme. It is shown that,
      in the absence of nitrate, the enzyme is very stable in vivo. Upon transfer from
      nitrate to ammonium medium, synthesis of nitrate reductase is reduced below the
      limits of defection. These effects are separate from the reversible (ferricyanide
      reactivatable) inactivation of the enzyme which is also observed. 

PMID- 24310897
TI  - Regulation of adenylate levels in intact spinach chloroplasts.
AB  - Adenylate levels and oxygen evolution in isolated intact spinach chloroplasts
      were measured in the presence of nitrite or oxaloacetate, which do not consume
      ATP during reduction, and of bicarbonate and glycerate the reduction of which
      requires ATP. The following results were obtained: 1. In chloroplasts incubated
      in the dark with nitrite, oxaloacetate or bicarbonate, the concentration of AMP
      was high and that of ATP low. The concentration of ADP was usually but not always
      lower than that of AMP. Light induced a rapid increase in the level of ATP which
      was accompained by a marked decrease in AMP and a slight decrease in ADP. The
      ratio of ATP/ADP rarely increased above 3 in the light, even in the absence of
      ATP consumption. Glycerate differed from other substrates in that it drastically
      decreased the chloroplast ATP level in the dark and kept its concentration low,
      even under illumination. The rate of glycerate-dependent oxygen evolution was
      high. 2. Mass action ratios (ATP) (AMP)/(ADP)(2) were close to 0.5 in the dark
      and in the presence of various substrates, except glycerate, indicating that
      adenylates were close to adenylate kinase equilibrium. When CO2 served as the
      substrate, (ATP) (AMP)/(ADP)(2) values were often higher than 0.5 in the light.
      In the presence of glycerate, the values were always much below 0.5. 3. The
      energy charge [2(ATP)+(ADP)]/2[(ATP) +(ADP)+(AMP)] of the chloroplast adenylate
      system was between 0.27 and 0.6 in the dark. It increased, but scarcely exceeded
      0.8, in the light. Energy charge was usually higher with bicarbonate than with
      phosphoglycerate, and always low with glycerate, both in the dark and in the
      light. 

PMID- 24310898
TI  - The interaction of auxin and cytokinin in the induction of phenylalanine ammonia
      lyase in suspension cultures of Phaseolus vulgaris.
AB  - The dependence of phenylalanine ammonialyase (PAL) induction in bean suspension
      cultures on the concentration of naphthylacetic acid (NAA) and kinetin has been
      investigated and the timing of the effect of each hormone has been determined.
      NAA was required at an optimal concentration of 1 mg l(-1) 2 days prior to the
      increase in PAL activity. Kinetin caused a prapid stimulation of the rate of PAL
      induction and the total amount of PAL induced in a concentration range of 0.1-0.5
      mg l(-1) when it was supplied to the cells immediately prior to the expected rise
      in PAL activity. The inhibitory effect of 2 mg l(-1) NAA on PAL induction was
      overcome by an increased concentration of kinetin. 

PMID- 24310899
TI  - Ethylene-promoted adventitious rooting and development of cortical air spaces
      (aerenchyma) in roots may be adaptive responses to flooding in Zea mays L.
AB  - The roots and stem base of intact, 10 day old maize (Zea mays L. cv. LG11)
      plants, grown in nutrient solution, were continuously aerated either with
      ethylene (5 MUl l(-1)) in air or with air alone. Ethylene treatment hastened the
      emergence of adventitious (nodal) roots from the base of the shoot, but slowed
      their subsequent extension. Ethylene also promoted the collapse of cells in the
      cortex of these roots, with lysigenous development of prominent air spaces
      (aerenchyma). Non-aeration of the nutrient solution caused endogenously produced
      ethylene to accumulate in the roots, and stimulated both the emergence of
      adventitious roots and the formation of cortical air spaces in them. With non
      aeration the concentration of oxygen did not fall below 1% in the equilibrium gas
      phase (air=20.8%). Complete deoxygenation of the nutrient solution, produced by
      passing oxygen-free nitrogen gas, prevented both air space formation and the
      evolution of ethylene by root segments.These results suggest that adventitious
      rooting and cortical air space formation in nodal roots in Zea mays may be
      stimulated by enhanced concentrations of endogenous ethylene arising either from
      entrapment of the gas by unstirred water layers around the roots and/or by
      increased biosynthesis. These responses are considered conducive to survival in
      waterlogged soil. 

PMID- 24310900
TI  - Involvement of a lipid-linked intermediate in the transfer of galactose from UDP
      [(14)C]galactose to exogenous protein in castor bean endosperm homogenates.
AB  - A crude organelle preparation from germinating castor bean endosperm catalysed
      the incorporation of galactose from UDP[(14)C]galactose into chloroform/methanol
      (2:1)-soluble glactolipids. At least two galactolipids were formed. Most of the
      [(14)C]galactose was present in a galactolipid synthesized by the microsomal
      membranes, the remainder was present in a second galactolipid synthesized by
      other cellular membranes, possibly Golgi-derived. The addition of asialo-agalacto
      fetuin reduced incorporation of [(14)C]galactose into the microsomal galactolipid
      with a concomitant increase in microsomal [(14)C]galactoprotein. Asialo-agalacto
      fetuin did not affect galactolipid or galactoprotein synthesis by nonmicrosomal
      fractions. The results suggest that the endoplasmic reticulum is a major site of
      protein galactosylation in castor bean endosperm cells, and that galactose
      transfer from UDP-galactose to protein occurs via a lipid-linked intermediate. 

PMID- 24310901
TI  - Short-time exposure to mono-n-butyl phthalate (MBP)-induced oxidative stress
      associated with DNA damage and the atrophy of the testis in pubertal rats.
AB  - Phthalates are widely used as plasticizer in various consumer domestic products
      and are known to disturb the male reproductive function in rodents. This study
      investigated the involvement of oxidative stress and the atrophy of the testes in
      pubertal rats exposed to mono-n-butyl phthalate (MBP). Four-week-old pubertal
      male rats were separated into three groups. In group I, 21 rats were fed rat chow
      containing 2 % MBP for 3 days. In group II, 21 rats were fed rat chow containing
      2 % MBP for 3 days and antioxidant vitamins C (250 mg/kg/day) and E (50
      mg/kg/day) were injected daily. In group III, 21 rats were fed standard rat chow
      and used as controls. After 3 days, each testis was weighed and the germ cell
      development was evaluated using the Johnsen score. The urinary 8-hydroxy-2'
      deoxyguanosine (8-OHdG) levels were measured as a biological marker of oxidative
      DNA damage. The mean testis weight was significantly lower for group I than
      groups II or III (p < 0.05). The mean Johnsen score was significantly lower for
      group I than for groups II or III (p < 0.05). Urinary 8-OHdG concentrations were
      higher in group I than in groups II or III. Short-time exposure to MBP may
      therefore induce oxidative DNA damage in rat testes, while antioxidant vitamins
      administered during exposure may protect against this stress.

PMID- 24310902
TI  - Determination of clindamycin and its metabolite clindamycin sulfoxide in diverse
      sewage samples.
AB  - In a research project on risk management of harmful substances in water cycles,
      clindamycin and 12 further antibiotics were determined in different sewage
      samples. In contrast to other antibiotics, an increase of the clindamycin
      concentration in the final effluent in comparison to the influent of the sewage
      treatment plant (STP) was observed. A back transformation from the main
      metabolite clindamycin sulfoxide to clindamycin during the denitrification
      process has been discussed. Therefore, the concentration of this metabolite was
      measured additionally. Clindamycin sulfoxide was stable in the STP and the
      assumption of back transformation of the metabolite to clindamycin was confuted.
      To explain the increasing clindamycin concentration in the STP, the ratio of
      clindamycin sulfoxide to clindamycin was observed. The ratio increased in dry
      spells with concentrated samples and with long dwell time in the sewer system. A
      short hydraulic retention in waste water system and diluted samples in periods of
      extreme rainfall lead to a lower ratio of clindamycin sulfoxide to clindamycin
      concentration. A plausible explanation of this behavior could be that clindamycin
      was adsorbed strongly to a component of the sewage during this long residence
      time and in the STP, clindamycin was released. In the common sample preparation
      in the lab, clindamycin was not released. Measurements of clindamycin and
      clindamycin sulfoxide in the influent and effluent of STP is advised for sewage
      monitoring. 

PMID- 24310903
TI  - Effects of climate change on surface-water photochemistry: a review.
AB  - Information concerning the link between surface-water photochemistry and climate
      is presently very scarce as only a few studies have been dedicated to the
      subject. On the basis of the limited knowledge that is currently available, the
      present inferences can be made as follows: (1) Warming can cause enhanced
      leaching of ionic solutes from the catchments to surface waters, including
      cations and more biologically labile anions such as sulphate. Preferential
      sulphate biodegradation followed by removal as organic sulphides in sediment
      could increase alkalinity, favouring the generation of the carbonate radical, CO3
      (.-). However, this phenomenon would be easily offset by fluctuations of the
      dissolved organic carbon (DOC), which is strongly anticorrelated with CO3 (.-).
      Therefore, obtaining insight into DOC evolution is a key issue in understanding
      the link between photochemistry and climate. (2) Climate change could exacerbate
      water scarcity in the dry season in some regions. Fluctuations in the water
      column could deeply alter photochemistry that is usually favoured in shallower
      waters. However, the way water is lost would strongly affect the prevailing
      photoinduced processes. Water outflow without important changes in solute
      concentration would mostly favour reactions induced by the hydroxyl and carbonate
      radicals (.OH and CO3 (.-)). In contrast, evaporative concentration would enhance
      reactions mediated by singlet oxygen ((1)O2) and by the triplet states of
      chromophoric dissolved organic matter ((3)CDOM*). (3) In a warmer climate, the
      summer stratification period of lakes would last longer, thereby enhancing
      photochemical reactions in the epilimnion but at the same time keeping the
      hypolimnion water in the dark for longer periods.

PMID- 24310904
TI  - SoilTrEC: a global initiative on critical zone research and integration.
AB  - Soil is a complex natural resource that is considered non-renewable in policy
      frameworks, and it plays a key role in maintaining a variety of ecosystem
      services (ES) and life-sustaining material cycles within the Earth's Critical
      Zone (CZ). However, currently, the ability of soil to deliver these services is
      being drastically reduced in many locations, and global loss of soil ecosystem
      services is estimated to increase each year as a result of many different
      threats, such as erosion and soil carbon loss. The European Union Thematic
      Strategy for Soil Protection alerts policy makers of the need to protect soil and
      proposes measures to mitigate soil degradation. In this context, the European
      Commission-funded research project on Soil Transformations in European Catchments
      (SoilTrEC) aims to quantify the processes that deliver soil ecosystem services in
      the Earth's Critical Zone and to quantify the impacts of environmental change on
      key soil functions. This is achieved by integrating the research results into
      decision-support tools and applying methods of economic valuation to soil
      ecosystem services. In this paper, we provide an overview of the SoilTrEC
      project, its organization, partnerships and implementation. 

PMID- 24310905
TI  - The impact of infield biomass burning on PM levels and its chemical composition.
AB  - In the South of Italy, it is common for farmers to burn pruning waste from olive
      trees in spring. In order to evaluate the impact of the biomass burning source on
      the physical and chemical characteristics of the particulate matter (PM) emitted
      by these fires, a PM monitoring campaign was carried out in an olive grove. Daily
      PM10 samples were collected for 1 week, when there were no open fires, and when
      biomass was being burned, and at two different distances from the fires.
      Moreover, an optical particle counter and a polycyclic aromatic hydrocarbon (PAH)
      analyzer were used to measure the high time-resolved dimensional distribution of
      particles emitted and total PAHs concentrations, respectively. Chemical analysis
      of PM10 samples identified organic and inorganic components such as PAHs, ions,
      elements, and carbonaceous fractions (OC, EC). Analysis of the collected data
      showed the usefulness of organic and inorganic tracer species and of PAH
      diagnostic ratios for interpreting the impact of biomass fires on PM levels and
      on its chemical composition. Finally, high time-resolved monitoring of particle
      numbers and PAH concentrations was performed before, during, and after biomass
      burning, and these concentrations were seen to be very dependent on factors such
      as weather conditions, combustion efficiency, and temperature (smoldering versus
      flaming conditions), and moisture content of the wood burned.

PMID- 24310906
TI  - Photodegradation of gaseous acetaldehyde and methylene blue in aqueous solution
      with titanium dioxide-loaded activated carbon fiber polymer materials and aquatic
      plant ecotoxicity tests.
AB  - TiO2-supported activated carbon felts (TiO2-ACFTs) were prepared by dip coating
      of felts composed of activated carbon fibers (ACFs) with either polyester fibers
      (PS-A20) and/or a polyethylene pulp (PE-W15) in a TiO2 aqueous suspension
      followed by calcination at 250  degrees C for 1 h. The as-prepared TiO2-ACFTs
      with 29-35 wt.% TiO2 were characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), and N2 adsorption. The TiO2-ACFT(PS-A20) samples with
      0 and 29 wt.% TiO2 were microporous with specific surface areas (S BET) of 996
      and 738 m(2)/g, respectively, whereas the TiO2-ACFT(PE-W15) samples with 0 and 35
      wt.% TiO2 were mesoporous with S BET of 826 and 586 m(2)/g, respectively.
      Adsorption and photocatalytic activity of the as-prepared samples were evaluated
      by measuring adsorption in the dark and photodegradation of gaseous acetaldehyde
      (AcH) and methylene blue (MB) in aqueous solution under UV light. The TiO2
      loading caused a considerable decrease in the S BET and MB adsorption capacity
      along with an increase in MB photodegradation and AcH mineralization. Lemna minor
      was chosen as a representative aquatic plant for ecotoxicity tests measuring
      detoxification of water obtained from the MB photodegradation reaction with the
      TiO2-ACFT samples under UV light.

PMID- 24310909
TI  - Parental marital status and adolescents' optimism about their future.
AB  - This article reports the results of a questionnaire survey of a representative
      random sample of all the schooled French-speaking adolescents of Montreal
      (N=4539). The sample included adolescents from legally intact homes, separated or
      divorced homes, and homes in which a parent was deceased. Three indicators of
      future success were included; adolescents from both types of broken families were
      less optimistic on all three dimensions than were adolescents from intact
      families. These results are discussed within a socioeconomic framework. 

PMID- 24310910
TI  - Occupations and attitudes of former student activists 10 years later.
AB  - Respondents in a 1969 survey (N=400)of undergraduate men at the University of
      Michigan were resurveyed as alumni in 1979 (N=215).Of the 400 surveyed in 1969,
      50 were active in political organizations ("organization activists") and 57 had
      been in demonstrations. These were rank- and-file student activists in the 1960s,
      not leaders. The demonstration activists were the more extreme in attitudes in
      both 1969 and 1979. In 1979 the demonstration activists were still more
      interested in political affairs than the nonactivists, more suspicious of free
      enterprise ideology, more opposed to current fears of communism, and more
      alienated from the military. Former organization activists were
      disproportionately employed in the human services areas of government,
      disproportionately absent from the business sector. In 1979 the former activists
      were no longer critical of the universities or of American society as a producer
      of poverty. They had shifted their main involvement from national to community
      affairs. While still distinctive in some attitudes, they were generally less
      radical than earlier. 

PMID- 24310908
TI  - Systematic review of severe fever with thrombocytopenia syndrome: virology,
      epidemiology, and clinical characteristics.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in
      China in 2010, followed by several reports from many other countries worldwide.
      SFTS virus (SFTSV) has been identified as the causative agent of the disease and
      has been recognized as a public health threat. This novel Bunyavirus belongs to
      the Phlebovirus genus in the family Bunyaviridae. This review also describes the
      different aspects of virology, pathogenesis, epidemiology, and clinical symptoms
      on the basis of the published article surveillance data and phylogenetic analyses
      of viral sequences of large, medium, and small segments retrieved from database
      using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3
      software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and
      considerable changes in several serum biomarkers. The disease has 10~15%
      mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly
      reported in the rural areas of Central and North-Eastern China, with seasonal
      occurrence from May to September, mainly targeting those of >=50 years of age. A
      wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs,
      and chickens have been proven seropositive for SFTSV. Ticks, especially
      Haemaphysalis longicornis, are suspected to be the potential vector, which have a
      broad animal host range in the world. More studies are needed to elucidate the
      vector-animal-human ecological cycle, the pathogenic mechanisms in high level
      animal models and vaccine development.

PMID- 24310911
TI  - Components of loneliness during adolescence.
AB  - Predictors of adolescent loneliness were investigated in two samples of high
      school students (n=92)and college undergraduates (n=192).Results were similar
      across samples. Among the high school sample loneliness was significantly
      predicted by a combination of alienation, a lack of social facility and
      acceptance, inferiority feelings, negative school attitudes, and a lack of social
      integration. Among college students loneliness was negatively related to social
      facility, regularity, approval, and involvement and positively related to
      alienation, parental disinterest, negative school attitudes, and inferiority
      feelings. 

PMID- 24310907
TI  - Antidepressants reduce neuroinflammatory responses and astroglial alpha-synuclein
      accumulation in a transgenic mouse model of multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the
      pathological accumulation of alpha-synuclein (alpha-syn) within oligodendroglial
      cells. This accumulation is accompanied by neuroinflammation with astrogliosis
      and microgliosis, that leads to neuronal death and subsequent parkinsonism and
      dysautonomia. Antidepressants have been explored as neuroprotective agents as
      they normalize neurotrophic factor levels, increase neurogenesis and reduce
      neurodegeneration, but their anti-inflammatory properties have not been fully
      characterized. We analyzed the anti-inflammatory profiles of three different
      antidepressants (fluoxetine, olanzapine and amitriptyline) in the MBP1-halpha-syn
      transgenic (tg) mouse model of MSA. We observed that antidepressant treatment
      decreased the number of alpha-syn-positive cells in the basal ganglia of 11-month
      old tg animals. This reduction was accompanied with a similar decrease in the
      colocalization of alpha-syn with astrocyte markers in this brain structure.
      Consistent with these results, antidepressants reduced astrogliosis in the
      hippocampus and basal ganglia of the MBP1-halpha-syn tg mice, and modulated the
      expression levels of key cytokines that were dysregulated in the tg mouse model,
      such as IL-1beta. In vitro experiments in the astroglial cell line C6 confirmed
      that antidepressants inhibited NF-kappaB translocation to the nucleus and reduced
      IL-1beta protein levels. We conclude that the anti-inflammatory properties of
      antidepressants in the MBP1-halpha-syn tg mouse model of MSA might be related to
      their ability to inhibit alpha-syn propagation from oligodendrocytes to astroglia
      and to regulate transcription factors involved in cytokine expression. Our
      results suggest that antidepressants might be of interest as anti-inflammatory
      and alpha-syn-reducing agents for MSA and other alpha-synucleinopathies.

PMID- 24310912
TI  - Depression and suicidal ideation in early adolescents.
AB  - This study sought to determine to what extent depression in young adolescents
      could be predicted by a variety of demographic and personality measures. A sample
      of 132 adolescents enrolled in junior high school completed a biographical data
      sheet, short forms of the Beck Depression Inventory (BDI), a Sensation- Seeking
      Scale (SSS), the Family Environment Scale (FES), a social support index (SSI),
      and a life stress inventory (LSI). The nondepressed group differed from the
      depressed group on a variety of variables, and stepwise multiple regression
      suggested a significant relationship between depression and life stress and an
      inverse relationship between depression and family cohesion. 

PMID- 24310913
TI  - Substance abuse minimization: Conceptualizing prevention in adolescent and youth
      programs.
AB  - This article provides an overview of the historical and theoretical work on
      adolescent substance abuse with implications for preventive interventions. The
      focus is on an illustration of the use of four basic prevention tools: education,
      competency promotion, community mobilization, and natural care giving. 

PMID- 24310914
TI  - Evidence of phase transition in Nd3+ doped phosphate glass determined by thermal
      lens spectrometry.
AB  - Thermal lens spectroscopy (TLS), differential scanning calorimetry (DSC) and
      Fourier transform infrared (FTIR) techniques were applied to the thermo-optical
      property analysis of a new phosphate glass matrix PANK with nominal composition
      40P2O5.20Al2O3.35Na2O.5K2O (mol%), doped with different Nd(3+) compositions. This
      glass system, synthesized by the fusion protocol, presents high transparency from
      UV to the near infrared, excellent thermo-optical properties at room temperature
      and high fluorescence quantum efficiency. Thermal lens phase shift parameters,
      thermal diffusivity and the DSC signal present pronounced changes at about 61 
      degrees C for the PANK glass system. This anomalous behavior was associated with
      a phase transition in the nanostructured glass materials. The FTIR signal
      confirms the presence of isolated PO4 tetrahedron groups connected to different
      cations in PANK glass. As a main result, our experimental data suggest that these
      tetrahedron groups present a structural phase transition, paraelectric
      ferroelectric phase transition, similar to that in potassium dihydrogen
      phosphate, KH2PO4, nanocrystals and which TLS technique can be used as a
      sensitive method to investigate changes in the structural level of nanostructured
      materials. 

PMID- 24310916
TI  - Enhancing physicians' use of clinical guidelines.

PMID- 24310915
TI  - Potential increased risk of cancer from commonly used medications: an umbrella
      review of meta-analyses.
AB  - Several commonly used medications have been associated with increased cancer risk
      in the literature. Here, we evaluated the strength and consistency of these
      claims in published meta-analyses. We carried out an umbrella review of 74 meta
      analysis articles addressing the association of commonly used medications
      (antidiabetics, antihyperlipidemics, antihypertensives, antirheumatics, drugs for
      osteoporosis, and others) with cancer risk where at least one meta-analysis in
      the medication class included some data from randomized trials. Overall, 51
      articles found no statistically significant differences, 13 found some decreased
      cancer risk, and 11 found some increased risk (one reported both increased and
      decreased risks). The 11 meta-analyses that found some increased risks reported
      16 increased risk estimates, of which 5 pertained to overall cancer and 11 to
      site-specific cancer. Six of the 16 estimates were derived from randomized trials
      and 10 from observational data. Estimates of increased risk were strongly
      inversely correlated with the amount of evidence (number of cancer cases)
      (Spearman's correlation coefficient = -0.77, P < 0.001). In 4 of the 16 topics,
      another meta-analysis existed that was larger (n = 2) or included better
      controlled data (n = 2) and in all 4 cases there was no statistically
      significantly increased risk of malignancy. No medication or class had
      substantial and consistent evidence for increased risk of malignancy. However,
      for most medications we cannot exclude small risks or risks in population
      subsets. Such risks are unlikely to be possible to document robustly unless very
      large, collaborative studies with standardized analyses and no selective
      reporting are carried out. 

PMID- 24310917
TI  - Novel mineralized heparin-gelatin nanoparticles for potential application in
      tissue engineering of bone.
AB  - Nanoparticles (NPs) were prepared from succinylated gelatin (s-GL) cross-linked
      with aldehyde heparin (a-HEP) and used subsequently as a nano-template for the
      mineralization of hydroxyapatite (HAP). Gelatin was functionalized with succinyl
      groups that made it soluble at room temperature. Heparin was oxidized to generate
      aldehyde groups and then used as a cross-linker that can react with s-GL to form
      NPs via Schiff's base linkage. The polymer concentrations, feed molar ratios and
      pH conditions were varied to fabricate NPs suspension. NPs were obtained with a
      spheroid shape of an average size of 196 nm at pH 2.5 and 202 nm at pH 7.4. These
      NPs had a positive zeta potential of 7.3 +/- 3.0 mV and a narrow distribution
      with PDI 0.123 at pH 2.5, while they had a negative zeta potential of -2.6 +/-
      0.3 mV and formed aggregates (PDI 0.257) at pH 7.4. The NPs prepared at pH 2.5
      with a mean particle size of 196 nm were further used for mineralization studies.
      The mineralization process was mediated by solution without calcination at 37 
      degrees C. The HAP formed on NPs was analyzed by Fourier transform infrared
      spectroscopy and X-ray diffraction. HAP coated s-GL/a-HEP NPs developed in this
      study may be used in future as osteoinductive fillers enhancing the mechanical
      properties of injectable hydrogel or use as potential multifunctional device for
      nanotherapeutic approaches. 

PMID- 24310918
TI  - Impedance matched channel walls in acoustofluidic systems.
AB  - Acoustophoresis in bulk acoustic wave (BAW) devices typically operates with an
      ultrasonic standing wave in a microfluidic channel between two opposing silicon
      walls, which act as both the acoustic and the fluidic boundary. In this paper, we
      describe BAW devices with an additional material layer of polydimethylsiloxane
      (PDMS). This PDMS wall is introduced to decouple the acoustic boundary (silicon
      wall) from the fluidic boundary (PDMS wall) by acoustic impedance matching. The
      acoustic field and the resulting particle manipulation are thereby less
      restricted than in conventional BAW devices. In the presented devices, particle
      accumulation lines can be placed arbitrarily within the fluidic domain, which
      strongly increases the possibility of acoustophoresis. The paper covers
      experimental results, an analytical model in good agreement and microfabrication
      techniques for PDMS enclosed in a microchannel. An application example for
      microparticle concentration is demonstrated. The presented approach offers
      further potential for biotechnological applications such as particle separation,
      enhanced particle sensors and cell handling. 

PMID- 24310919
TI  - Atypical location of intracranial germinoma: a case report.

PMID- 24310920
TI  - Association between job strain (high demand-low control) and cardiovascular
      disease risk factors among petrochemical industry workers.
AB  - OBJECTIVE: One of the practical models for assessment of stressful working
      conditions due to job strain is "job demand and control" or Karasek's job strain
      model. This model explains how adverse physical and psychological effects
      including cardiovascular disease risk factors can be established due to high work
      demand. The aim was to investigate how certain cardiovascular risk factors
      including body mass index (BMI), heart rate, blood pressure, serum total
      cholesterol levels, and cigarette smoking are associated with job demand and
      control in workers. MATERIALS AND METHODS: In this cohort study, 500 subjects
      completed "job demand and control" questionnaires. Factor analysis method was
      used in order to specify the most important "job demand and control" questions.
      Health check-up records of the workers were applied to extract data about
      cardiovascular disease risk factors. Ultimately, hypothesis testing, based on
      Eta, was used to assess the relationship between separated working groups and
      cardiovascular risk factors (hypertension and serum total cholesterol level).
      RESULTS: A significant relationship was found between the job demand-control
      model and cardiovascular risk factors. In terms of chi-squared test results, the
      highest value was assessed for heart rate (Chi(2) = 145.078). The corresponding
      results for smoking and BMI were Chi(2) = 85.652 and Chi(2) = 30.941,
      respectively. Subsequently, Eta result for total cholesterol was 0.469, followed
      by hypertension equaling 0.684. Moreover, there was a significant difference
      between cardiovascular risk factors and job demand-control profiles among
      different working groups including the operational group, repairing group and
      servicing group. CONCLUSION: Job control and demand are significantly related to
      heart disease risk factors including hypertension, hyperlipidemia, and cigarette
      smoking.

PMID- 24310921
TI  - An overview of occupational voice disorders in Poland.
AB  - Occupational voice disorders make the most frequently certified category of
      occupational diseases in Poland, making up approximately 20% of all cases. This
      study presents the current knowledge of the etiopathogenesis of occupational
      voice disorders. It stresses the importance of the evaluation of vocal loading by
      means of objective measurements. Furthermore, this study discusses the medico
      legal aspects of the procedure of certifying occupational voice disorders in
      Poland. The paper also describes the preventive programs addressed particularly
      to teachers, including multidisciplinary and holistic management of occupational
      dysphonia. Their role in the improvement of occupational safety and health (OSH)
      arrangement for vocally demanding professions is emphasized. 

PMID- 24310922
TI  - Association between a biomarker of exposure to polycyclic aromatic hydrocarbons
      and semen quality.
AB  - OBJECTIVES: Growing evidence supports the reproductive and developmental toxicity
      of polycyclic aromatic hydrocarbons (PAHs) from prenatal and postnatal exposure,
      but the results of epidemiological studies regarding harmful effects of PAHs
      exposure on male reproductive system still remain limited and inconclusive. The
      aim of the present study was to investigate the relationship between 1
      hydroxypyrene, a biomarker of polycyclic aromatic hydrocarbons exposure and semen
      quality. MATERIALS AND METHODS: The study population consisted of 277 men
      attending an infertility clinic for diagnostic purposes and having normal semen
      concentration of 20-300 mln/ml or slight oligozoospermia (semen concentration: 15
      20 mln/ml) (WHO 1999). All the men were healthy and under 45 years of age. All
      participants were interviewed and provided a semen sample. The interview included
      questions concerning demographics, socio-economic status, medical history related
      to past diseases which may have an impact on semen quality, lifestyle factors and
      occupational information. Concentrations of 1-hydroxypyrene (1-OHP) in the urine
      samples were analyzed using high performance liquid chromatography (HPLC).
      RESULTS: A positive association was found between the level of 1-OHP in urine and
      sperm neck abnormalities as well as the percentage of static sperm cells (p =
      0.001, p = 0.018, respectively). Additionally, exposure to PAHs measured by 1-OHP
      in urine decreased semen volume and the percentage of motile sperm cells (p =
      0.014, p = 0.0001, respectively). CONCLUSIONS: Presented findings indicate that
      the environmental level of PAHs exposure adversely affects male semen quality.
      The future large-scale studies should incorporate different biomarkers to
      generate a more accurate and full assessment of the effects of PAHs exposure on
      male fertility.

PMID- 24310923
TI  - Motor neuron activation in peripheral nerves using infrared neural stimulation.
AB  - OBJECTIVE: Localized activation of peripheral axons may improve selectivity of
      peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized
      delivery to activate neural tissue. This study investigated INS to determine
      whether localized delivery limited functionality in larger mammalian nerves.
      APPROACH: The rabbit sciatic nerve was stimulated extraneurally with 1875 nm
      wavelength infrared light, electrical stimulation, or a combination of both.
      Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG)
      recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and
      Tibialis Anterior were the primary output measures. Stimulation applied included
      infrared-only, electrical-only, and combined infrared and electrical. MAIN
      RESULTS: 81% of nerves tested were sensitive to INS, with 1.7 +/- 0.5 ISR
      detected per nerve. INS was selective to a single muscle within 81% of identified
      ISR. Activation energy threshold did not change significantly with stimulus
      power, but motor activation decreased significantly when radiant power was
      decreased. Maximum INS levels typically recruited up to 2-9% of any muscle.
      Combined infrared and electrical stimulation differed significantly from
      electrical recruitment in 7% of cases. SIGNIFICANCE: The observed selectivity of
      INS indicates that it may be useful in augmenting rehabilitation, but significant
      challenges remain in increasing sensitivity and response magnitude to improve the
      functionality of INS.

PMID- 24310924
TI  - TLR4/PKC-mediated tight junction modulation: a clinical marker of chemotherapy
      induced gut toxicity?
AB  - Chemotherapy-induced gut toxicity is a major clinical and economic burden to
      oncology practice. The mechanisms responsible for its development are ill
      defined, hampering the development of therapeutic interventions. In light of
      newly published research foci and clinical practice guidelines in supportive care
      in cancer, there has been renewed interest in the role tight junctions play in
      the pathobiology of chemotherapy-induced gut toxicity. Several preclinical
      studies have identified molecular defects in intestinal tight junctions following
      chemotherapy. Despite these findings, the mechanisms responsible for chemotherapy
      induced tight junction disruption remain unclear. Recent research has highlighted
      roles for toll-like receptor 4 and protein kinase C signalling in the regulation
      of tight junctions. This critical review therefore aims to provide evidence
      linking toll-like receptor 4 expression, protein kinase C activation and tight
      junction disruption and their relationship to clinical toxicity. 

PMID- 24310925
TI  - Respiratory effects of bioaerosols: exposure-response study among salmon
      processing workers.
AB  - OBJECTIVES: The aim of the study was to determine exposure-response relationships
      in salmon-processing workers. METHODS: Cross-shift FEV1, acute respiratory
      symptoms, and exposure to total protein, parvalbumin and endotoxin were main
      variables measured during one workweek. Exposure-response relationships were
      analyzed by Generalized Estimation Equations of cross-week data and by multiple
      regressions of day-to-day data. RESULTS: Exposure levels were higher in those
      workers who reported use of water hose. GEE showed negative coefficients for
      interaction between TP exposure and time (days) on cross-week change of FEV1.
      Multiple regressions showed significant associations between TP levels and cross
      shift change of FEV1 and symptoms (cough, chest tightness) only for Monday
      shifts. CONCLUSIONS: A tolerance effect during the course of a workweek is
      suggested. Use of water hose is a risk process with regard to the liberation of
      measured components of bioaerosols.

PMID- 24310928
TI  - Short and sweet: (D)-glucose to (L)-glucose and (L)-glucuronic acid.
AB  - The scarcity and expense of access to L-sugars and other rare sugars have
      prevented the exploitation of their biological potential; for example D-psicose,
      only recently available, has been recognized as an important new food. Here we
      give the definitive and cheap synthesis of 99.4% pure L-glucose from D-glucose
      which requires purification of neither intermediates nor final product other than
      extraction into and removal of solvents; a simple crystallization will raise the
      purity to >99.8%. 

PMID- 24310926
TI  - Prospective evaluation of anatomic patellofemoral inlay resurfacing: clinical,
      radiographic, and sports-related results after 24 months.
AB  - PURPOSE: To prospectively evaluate the clinical, radiographic, and sports-related
      outcomes at 24 months after isolated and combined patellofemoral inlay
      resurfacing (PFIR). METHODS: Between 2009 and 2010, 29 consecutive patients with
      patellofemoral osteoarthritis (OA) were treated with the HemiCAP((r)) Wave
      Patellofemoral Resurfacing System (Arthrosurface, Franklin, MA, USA). Based on
      preoperative findings, patients were divided into two groups: group I, isolated
      PFIR (n = 20); and group II, combined PFIR with concomitant procedures to address
      patellofemoral instability, patellofemoral malalignment, and tibiofemoral
      malalignment (n = 9). Patients were evaluated preoperatively and at 24 months
      postoperatively. Clinical outcomes included WOMAC, subjective IKDC, Pain VAS,
      Tegner activity score, and a self-designed sports questionnaire. Kellgren
      Lawrence grading was used to assess progression of tibiofemoral OA. The Caton
      Deschamps Index was used to assess differences in patellar height. RESULTS:
      Twenty-seven patients (93 %) were available for 24-month follow-up. Eighty-one
      per cent of the patients were either satisfied or very satisfied with the overall
      outcome. Significant improvements in the WOMAC, subjective IKDC, and Pain VAS
      were seen in the overall patient cohort and in both subgroups. The median Tegner
      score and sports frequency showed a significant increase in the overall patient
      cohort and in group II. The number of sports disciplines increased significantly
      in both subgroups. No significant progression of tibiofemoral OA or changes in
      patellar height were observed. CONCLUSION: Patellofemoral inlay resurfacing is an
      effective and safe procedure in patients with symptomatic patellofemoral OA.
      Significant improvements in functional scores and sports activity were found
      after both isolated and combined procedures. LEVEL OF EVIDENCE: Prospective case
      series, Level III.

PMID- 24310929
TI  - Time and dose of irrigation impact Tuber melanosporum ectomycorrhiza
      proliferation and growth of Quercus ilex seedling hosts in young black truffle
      orchards.
AB  - In Mediterranean climate, young truffle-oak orchards are subjected to drought
      episodes that can compromise the development of Tuber melanosporum. We
      investigated the responses of T. melanosporum to water supply in three periods:
      May to July, August to October, and May to October. In each period, five water
      doses were established: 0, 25, 50, 75, and 100% of the reference
      evapotranspiration (ETo). Five orchards were planted with Quercus ilex inoculated
      with T. melanosporum, and in each orchard, we arranged a two-factorial design
      with irrigation period and irrigation dose as main factors to test their combined
      effects on the development of both T. melanosporum and Q. ilex after 3 years in
      the field. Irrigation period significantly interacted with irrigation doses for
      the absolute presence per seedling of T. melanosporum mycorrhizae. Irrigation in
      May-July increased significantly T. melanosporum colonization in seedlings
      irrigated with 50% ETo dose compared to the 0% ETo dose. A similar pattern with
      smaller differences in means was observed in August-October period, but the
      irrigation doses did not change T. melanosporum colonization when we watered from
      May to October. We found ectomycorrhizae different from T. melanosporum in 51% of
      the seedlings studied, but their presence was marginal. Our results suggest that
      a moderate irrigation dose promotes seedling growth and number of fine root tips
      per unit of fine root length, which may be potentially colonized by T.
      melanosporum.

PMID- 24310932
TI  - A multilevel intermediate-band solar cell by InGaN/GaN quantum dots with a strain
      modulated structure.
AB  - Multiple stacked InGaN/GaN quantum dots are embedded into an InGaN p-n junction
      to develop multilevel intermediateband (MIB) solar cells. An IB transition is
      evidenced from both experiment and theoretical calculations. The MIB solar cell
      shows a wide photovoltaic response from the UV to the near-IR region. This work
      opens up an interesting opportunity for high-efficiency IB solar cells in the
      photovoltaics field.

PMID- 24310930
TI  - Proteome changes in Oncidium sphacelatum (Orchidaceae) at different trophic
      stages of symbiotic germination.
AB  - Mutualistic symbioses between plants and fungi are a widespread phenomenon in
      nature. Particularly in orchids, association with symbiotic fungi is required for
      seed germination and seedling development. During the initial stages of symbiotic
      germination, before the onset of photosynthesis, orchid protocorms are fully
      mycoheterotrophic. The molecular mechanisms involved in orchid symbiotic
      germination and development are largely unknown, but it is likely that changes in
      plant energy metabolism and defense-related responses play a central role in
      these processes. We have used 2D-LC-MS/MS coupled to isobaric tagging for
      relative and absolute quantification to identify proteins with differential
      accumulation in Oncidium sphacelatum at different stages of mycorrhizal protocorm
      development (achlorophyllous and green protocorms) after seed inoculation with a
      Ceratobasidium sp. isolate. We identified and quantified 88 proteins, including
      proteins putatively involved in energy metabolism, cell rescue and defense,
      molecular signaling, and secondary metabolism. Quantitative analysis showed that
      the expected changes in carbon metabolism in green protocorms were accompanied by
      enhanced accumulation of proteins involved in the modulation of reactive oxygen
      species homeostasis, defense-related responses, and phytoalexins and carotenoid
      biosynthesis. Our results suggest profound metabolic changes in orchid protocorms
      during the switch from the fully mycoheterotrophic to the photosynthetic stage.
      Part of these changes may be also related to the obligatory nature of the
      interaction with the endomycorrhizal fungus. 

PMID- 24310931
TI  - Caregivers' intentions to disclose HIV diagnosis to children living with HIV in
      South Africa: a theory-based approach.
AB  - When children know their HIV serostatus, they are more likely to cooperate with
      steps to manage their health and the risk of transmitting HIV to others. Mounting
      evidence indicates that caregivers often do not disclose to HIV-positive children
      that the children are living with HIV, but little is known about the modifiable
      determinants of pediatric HIV disclosure. The present study examined theory-of
      planned-behavior predictors of the intention to disclose to children their HIV
      diagnosis. The participants were 100 caregivers of HIV-positive children in
      Eastern Cape Province, South Africa. Proportional-odds logistic regression
      analysis revealed that normative support for disclosure and caregiver-child
      communication predicted the intention to disclose, whereas behavioral beliefs
      regarding the consequences of disclosing and self-efficacy to disclose did not.
      The results suggest that interventions to increase pediatric HIV disclosure in
      South Africa should help caregivers enlist support for disclosure among important
      referents and improve communication with their HIV-infected children. 

PMID- 24310933
TI  - A case of pancreatic agenesis and congenital heart defects with a novel GATA6
      nonsense mutation: evidence of haploinsufficiency due to nonsense-mediated mRNA
      decay.
AB  - Recently, GATA6 heterozygous loss-of-function mutations were reported to cause
      pancreatic agenesis and congenital heart defects (PACHD [OMIM:600001]). However,
      the molecular mechanisms resulting from premature termination codons have not
      been examined in this disorder. The objective of this study was to perform a
      genetic analysis of a patient with PACHD. A female patient presented with
      ventricular septal defect, patent ductus arteriosus, and congenital diaphragmatic
      hernia at birth. Permanent neonatal diabetes mellitus and pancreatic exocrine
      deficiency due to pancreatic agenesis was diagnosed at 1 month of age. PCR-direct
      sequencing of GATA6 revealed that the patient is heterozygous for a novel de novo
      nonsense mutation of c.1477C>T, p. Arg493X in exon 5. RT-PCR direct sequencing of
      the RT-PCR products of total RNA from peripheral blood of the patient for the
      region encompassing exons 4-6 revealed only the wild-type allele. This finding
      provides the evidence for the occurrence of nonsense-mediated mRNA decay (NMD) in
      the p.Arg493X mutation. Quantitative RT-PCR analysis revealed that the expression
      of GATA6 transcript in the patient was less than half compared with normal
      control samples. This is the first evidence that GATA6 haploinsufficiency is
      caused by NMD in vivo, and we conclude that GATA6 haploinsufficiency causes not
      only PACHD but may affect other organs derived from the endoderm. Further
      screenings of GATA6 mutations in patients with various forms of diabetes and/or
      congenital heart disease with other visceral malformation may reveal the impact
      of GATA6 mutations on diabetes and congenital malformation.

PMID- 24310934
TI  - Diagnostic potential of anti-rNcp-43 polyclonal antibodies for the detection of
      Neospora caninum.
AB  - Neosporosis is a disease caused by the apicomplexan parasite Neospora caninum,
      which is closely related to Toxoplasma gondii. N. caninum infection represents an
      important cause of reproductive failure in sheep, goats, horses, and cattle
      worldwide. The diagnosis of neosporosis is based on the detection of pathogen
      specific antibodies in animal sera or the presence of tissue cysts. However,
      morphological similarities and serological cross-reactivity between N. caninum
      and T. gondii can result in the misdiagnosis. In this study, the N. caninum
      tachyzoite surface protein Ncp-43 was expressed in a recombinant form to elicit
      polyclonal antibodies (pAb) response. The pAb was purified and conjugated to
      horseradish peroxidase (HRP) or fluorescein isothiocyanate (FITC) to detect the
      recombinant and native Ncp-43 proteins, respectively. The pAb and pAb/HRP were
      able to recognize rNcp-43 by dot blot and ELISA, and pAb/FITC immunolabeled the
      apical complex of tachyzoites. A blocking enzyme-linked immunosorbent assay (b
      ELISA) was performed to evaluate pAb/HRP as a diagnostic tool. The mean percent
      inhibition for the positive and negative serum samples from cattle with
      neosporosis was significantly different (P < 0.0001). These results suggest that
      the pAb may bind to the same epitopes of Ncp-43 as anti-N. caninum antibodies in
      the positive samples tested. The b-ELISA using the pAb/HRP can facilitate
      diagnostic testing for neosporosis, since fewer steps are involved, and cross
      reactivity with secondary antibodies is avoided. In summary, this report
      describes the production of antibodies against N. caninum, and evaluates the
      potential of these tools for the development of new diagnostic tests for
      neosporosis. 

PMID- 24310935
TI  - Identification of genes required by Bacillus thuringiensis for survival in soil
      by transposon-directed insertion site sequencing.
AB  - Transposon-directed insertion site sequencing was used to identify genes required
      by Bacillus thuringiensis to survive in non-axenic plant/soil microcosms. A total
      of 516 genetic loci fulfilled the criteria as conferring survival
      characteristics. Of these, 127 (24.6 %) were associated with uptake and transport
      systems; 227 loci (44.0 %) coded for enzymatic properties; 49 (9.5 %) were gene
      regulation or sensory loci; 40 (7.8 %) were structural proteins found in the cell
      envelope or had enzymatic activities related to it and 24 (4.7 %) were involved
      in the production of antibiotics or resistance to them. Eighty-three (16.1 %)
      encoded hypothetical proteins or those of unknown function. The ability to form
      spores was a key survival characteristic in the microcosms: bacteria, inoculated
      in either spore or vegetative form, were able to multiply and colonise the soil,
      whereas a sporulation-deficient mutant was not. The presence of grass seedlings
      was critical to colonisation. Bacteria labelled with green fluorescent protein
      were observed to adhere to plant roots. The sporulation-specific promoter of
      spo0A, the key regulator of sporulation, was strongly activated in the
      rhizosphere. In contrast, the vegetative-specific promoters of spo0A and PlcR, a
      pleiotropic regulator of genes with diverse activities, were only very weakly
      activated. 

PMID- 24310936
TI  - Nucleotide sequences of the genes for the alpha, beta and epsilon subunits of
      wheat chloroplast ATP synthase.
AB  - The nucleotide sequences of the chloroplast genes for the alpha, beta and epsilon
      subunits of wheat chloroplast ATP synthase have been determined. Open reading
      frames of 1512 bp, 1494 bp and 411 bp are deduced to code for polypeptides of
      molecular weights 55201, 53796 and 15200, identified as the alpha, beta and
      epsilon subunits respectively by homology with the subunits from other sources
      and by amino acid sequencing of the epsilon subunit. The genes for the beta and
      epsilon subunits overlap by 4 bp. The gene for methionine tRNA is located 118 bp
      downstream from the epsilon subunit gene. Comparisons of the deduced amino acid
      sequences of the alpha and beta subunits with those from other species suggest
      regions of the proteins involved in adenine nucleotide binding. 

PMID- 24310937
TI  - Location, nucleotide sequence and expression of the proton-translocating subunit
      gene of theE. gracilis chloroplast ATP synthase.
AB  - A 1700 base pairHindIII restriction fragment from theE. gracilis chloroplast
      chromosome has been shown to contain the gene for the proton-translocating
      subunit of the ATP synthase (atpH). The gene was mapped by heterologous
      hybridization using internal sequences of the gene from wheat and spinach
      chloroplast DNA. Each chloroplast chromosome contains a single copy of atpH,
      which is located close to the gene for the alpha subunit of the ATP synthase
      (atpA). The nucleotide sequence of the gene is uninterrupted by introns. The
      predicted sequence of 77 amino acids is 70% homologous to that of the wheat and
      spinach polypeptides. The gene is expressedin vivo as shown by hybridization of
      atpH probes to cellulose nitrate filter blots of total chloroplast RNA. 5'
      proximal to the atpH locus on the clonedHindIII fragment are 38 codons from the
      carboxy terminus of an open reading frame which may be another ATP synthase
      subunit. Transcription of the ORF and the atpH gene may be as part of a large
      polycistronic mRNA. 

PMID- 24310938
TI  - Nucleotide sequence of the 17S-25S spacer region from rice rDNA.
AB  - The nucleotide sequence of a spacer region between rice 17S and 25S rRNA genes
      (rDNAs) has been determined. The coding regions for the mature 17S, 5.8S and 25S
      rRNAs were identified by sequencing terminal regions of these rRNAs. The first
      internal transcribed spacer (ITS1), between 17S and 5.8S rDNAs, is 194-195 bp
      long. The second internal transcribed spacer (ITS2), between 5.8S and 25S rDNAs,
      is 233 bp long. Both spacers are very rich in G+C, 72.7% for ITS1 and 77.3% for
      ITS2. The 5.8S rDNA is 163-164 bp long and similar in primary and secondary
      structures to other eukaryotic 5.8S rDNAs. The 5.8S rDNA is capable of
      interacting with the 5' terminal region of 25S rDNA. 

PMID- 24310939
TI  - The plastome of a brown alga,Dictyota dichotoma : I. Physical properties and the
      Bam HI/Sal I/Bgl II cleavage site map.
AB  - Plastids of the brown algaDictyota dichotoma contain a single homogeneous DNA
      species which bands at a buoyant density of 1.693 g/cm(3) in neutral CsCl
      equilibrium density gradients. The corresponding nuclear DNA has a density of
      1.715 g/cm(3). The molecular size of the plastid DNA is 123 kbp as calculated by
      both electron microscopy of spread intact circular molecules and gel
      electrophoresis following single and double digestions with various restriction
      enzymes. A restriction map has been constructed using the endonucleases Sal I,
      Bam HI, and Bgl II which cleave theDictyota plastome into 6, 12, and 17
      fragments, respectively. No large repeated regions, as found in chlorophycean
      andEuglena plastid DNAs, were detected.Dictyota dichotoma is the first member
      from the chlorophyll c-line of the algal pedigree for which a physical map of
      plastid DNA has been established. 

PMID- 24310940
TI  - Biogenesis of photosystem I reaction center during greening of oat, bean and
      spinach leaves.
AB  - The relative amounts of some chloroplast polypeptides were followed during
      greening of leaves from three different plant families. Oat, bean and spinach
      were the representatives of the Gramineae, Leguminosae and Chenopodiaceae,
      respectively. By using specific antibodies against subunits of the chloroplast
      protein complexes, it was found with that method that the protein complexes which
      are not involved in a photobiochemical reaction were synthesized in etiolated
      leaves and their amounts did not significantly change during greening. Examples
      of these are the large and small subunits of ribulose 1,5-bisphosphate
      carboxylase, the subunits of the chloroplast coupling factor (CF1) and cytochrome
      b6-f complex. On the other hand, in photosystem I reaction center, the synthesis
      of subunits II, III, IV and V was found to be induced by light. Sequential
      synthesis of these subunits was observed. Subunit II is the first to be
      synthesized after exposing the plants to light. The synthesis of subunits III, IV
      and V followed the synthesis of subunit II in this order. Subunit I of
      photosystem I reaction center was present in etiolated leaves and its amount was
      not significantly altered during the first few hours of greening. 

PMID- 24310941
TI  - Physical and genetic mapping of safflower chloroplast DNA : Location of psbA,
      rbcL, atpA and rrnA.
AB  - A physical map of safflower (Carthamus tinctorius L.) chloroplast DNA has been
      generated using SalI, PstI, KpnI and HindIII restriction endonucleases. The
      circular plastid genome (151 kbp) has the usual inverted repeat. Heterologous
      probes containing psbA, rbcL, atpA or rrnA structural genes mapped colinearly
      with spinach and other chloroplast genomes. 

PMID- 24310942
TI  - Variable presence of the 1.94kb mitochondrial plasmid in maizeS cytoplasm and its
      relationship to cytoplasmic male sterility.

PMID- 24310945
TI  - Six themes in search of authors.

PMID- 24310944
TI  - Post-radiation atypical vascular lesion/angiosarcoma arising in the larynx.
AB  - Atypical vascular lesions (AVL) and angiosarcomas (AS) are lesions known to arise
      after radiation therapy. These lesions can show overlap in both their gross and
      histologic pictures, and distinction between the two can be extremely challenging
      at times. They are known most commonly to arise in the breast region after
      radiation therapy. We present the first unique case of post-radiation AVL/AS
      arising in the larynx of a 51 year old woman, occurring 8 years after she
      received radiation for tonsillar squamous cell carcinoma. 

PMID- 24310943
TI  - Gradients versus dichotomies: how strength of semantic context influences event
      related potentials and lexical decision times.
AB  - In experiments devoted to word recognition and/or language comprehension,
      reaction time in the lexical decision task is perhaps the most commonly used
      behavioral dependent measure, and the amplitude of the N400 component of the
      event-related potential (ERP) is the most common neural measure. Both are
      sensitive to multiple factors, including frequency of usage, orthographic
      similarity to other words, concreteness of word meaning, and preceding semantic
      context. All of these factors vary continuously. Published results have shown
      that both lexical decision times and N400 amplitudes show graded responses to
      graded changes of word frequency and orthographic similarity, but a puzzling
      discrepancy in their responsivity to the strength of a semantic context has
      received little attention. In three experiments, we presented pairs of words
      varying in the strengths of their semantic relationships, as well as unrelated
      pairs. In all three experiments, N400 amplitudes showed a gradient from unrelated
      to weakly associated to strongly associated target words, whereas lexical
      decision times showed a binary division rather than a gradient across strengths
      of relationship. This pattern of results suggests that semantic context effects
      in lexical decision and ERP measures arise from fundamentally different
      processes. 

PMID- 24310946
TI  - The creative role of doubt in religion.
AB  - This essay contains four arguments in defense of the creative role of doubt in
      religion. Within a specified framework or context it is argued that: 1) creative
      doubt is a means of constructively acknowledging human finitude, 2) creative
      doubt can play a role in keeping one's fundamental beliefs alive and vital, 3)
      creative doubt, by continually challenging the full adequacy of religious
      symbols, serves as a check against the idolatrous worship of one's own religious
      language, and 4) the avoidance of doubt may reflect a relinquishing of freedom
      and a dehumanizing quest for certainty. 

PMID- 24310947
TI  - Symbols to grow on.
AB  - The importance of symbols in the communication of religious traditions is
      considered in order to develop a critique for enhancing their potential for
      facilitating integration and wholeness. Four questions are proposed: 1) What
      precise segment of one's experience comes into focus through the symbol employed?
      2) How is this experience related to the person? 3) What does the symbol
      contribute to self-identity? 4) How does the symbol reorient the person? In
      conclusion, an example is suggested from contemporary changes in the Roman
      Catholic Eucharistic liturgy. 

PMID- 24310948
TI  - James Hillman: Toward a poetic psychology.
AB  - InThe Dream and the Underworld James Hillman continues to deepen and to refine
      Jung's recovery of the spontaneous image-making of the soul. Hillman's
      contribution lies in his "imaginai reduction"-relating of images to their
      archetypal background in Greek mythology. Myth is seen as the maker of the
      psyche, and, in turn, the soul-making ispoesis-a return to the imaginal and
      poetic basis of consciousness. Dreams, understood poetically, are neither
      messages to be deciphered and used for the benefit of the rational ego (Freud)
      nor compensatory to the ego (Jung); they are complete in themselves and must be
      allowed to speak for themselves. Hillman also sees dreams as initiations into the
      underworld of death-the other side of life where our imaginal substance is
      unobstructed by the literal and dualistic standpoints of the dayworld. 

PMID- 24310949
TI  - Wisdom and folly in death and dying.
AB  - This author presents the argument, in the context of homiletic reflections on
      Psalm 90?12, that psychosocial care for the terminally ill continues to be
      compromised by the anxiety and denial of the staff who provide such care. An
      illustrative case example is offered. An explanation is provided in terms of the
      support for such denial in the instrumental values of our technological culture.
      The work of Kubler-Ross is presented as an example of the religious function of
      science in modern culture. A paradoxical prescription, based on Psalm 90?12, is
      proposed as a solution to the problem. A postscript by a colleague of the author
      illustrates the subjective attitude of the staff advocated in the paradoxical
      prescription. 

PMID- 24310950
TI  - Postscript: Soliloquy upon approaching the bedside of a dying person.

PMID- 24310951
TI  - Transmigration, liminality, and spiritualist healing.
AB  - Observations made in an urban spiritualist organization in western New York led
      to the following conclusions. A symbolic event basic to this total belief system
      is the creation of a liminal state that allows church members to transcend the
      earth plane and experience an alternate reality, the spiritual world. The
      creation of this symbolic suspension serves to reinforce the basic belief system
      and legitimize the healing and message rituals. This paper will explore the
      church service as the symbolic event that serves to take church members into the
      liminal state. The transition occurs as a collective experience, culminating in
      the healing and message services. 

PMID- 24310952
TI  - The prostitutes' syndrome.
AB  - When female patients, at critical periods in their lives, receive suggestions
      regarding promiscuous and unacceptable behavior, they may at a later time in life
      act upon these suggestions. However, involvement in promiscuous sexual behavior
      results in guilt, which will often be seen clinically in the form of depressive
      neuroses or psychosomatic illness. Several case histories are presented, and
      implications for treatment are discussed. 

PMID- 24310953
TI  - Nursing: Significance for spiritual care.
AB  - Nurses can be seen to contribute significantly to the spiritual objectives and
      programs in hospitals and other health agencies under religious auspices. One
      impressive example is nursing involvement with and cooperation in the pastoral
      care program at North Carolina Baptist Hospital in Winston-Salem. At this
      hospital the nurse is both an assistant to and a coworker with the chaplain and
      functions in many ways as facilitator and supporter in his spiritual mission. 

PMID- 24310954
TI  - The beginning of the end of measles and rubella.

PMID- 24310955
TI  - Potential prognostic implications of whole-body bone marrow MRI in diffuse large
      B-cell lymphoma patients with a negative blind bone marrow biopsy.
AB  - PURPOSE: To assess the prognostic implications of whole-body bone marrow MRI
      findings in diffuse large B-cell lymphoma (DLBCL) patients with a negative blind
      bone marrow biopsy (BMB). MATERIALS AND METHODS: Thirty-eight patients with newly
      diagnosed DLBCL and negative blind BMB prospectively underwent whole-body MRI (T1
      weighted, T2-weighted short inversion time inversion recovery, and diffusion
      weighted sequences), which were scored as positive or negative for lymphomatous
      bone marrow involvement. Proportions of patients who experienced disease
      relapse/progression or died during follow-up were calculated and compared between
      whole-body MRI-positive and whole-body MRI-negative patients. RESULTS: The median
      follow-up time of surviving patients was 973 days (range, 391-1655 days). Disease
      relapse/progression occurred in 33% (5/15) of patients with a positive whole-body
      MRI and in 13% (3/23) of patients with a negative whole-body MRI. In addition,
      20% (3/15) of patients with a positive whole-body MRI died during follow-up,
      compared with 9% (2/23) of patients with a negative whole-body MRI. CONCLUSION:
      The results of this study show that disease relapse or progression and death may
      occur more frequently in whole-body MRI-positive patients than in whole-body MRI
      negative patients, which suggests that whole-body bone marrow MRI findings in
      DLBCL patients with a negative BMB may have prognostic implications.

PMID- 24310956
TI  - Early adolescents' significant others: Grade and gender differences in perceived
      relationships with familial and nonfamilial adults and young people.
AB  - In order to provide a fuller and more satisfying description of the significant
      others in the social world of an adolescent, the Social Relations Questionnaire
      was developed and then administered to almost 3000 seventh-through tenth-graders
      in a midwestern suburban school district. The sample was randomly split in half
      and analyses were run on both halves separately to test for replicability.
      Results indicated that parents and siblings are almost always listed as
      significant others by adolescents in all four grade levels. Furthermore, the
      majority of adolescents listed at least one extended family adult and at least
      one nonrelated adult as important in their lives. The nonrelated adults lived
      closer to the adolescents and were seen more frequently and in more contexts than
      extended family members. Fewer extended family adults were listed in the older
      grades. Females listed more significant others than males both overall and in
      terms of both same- and opposite-sex nonrelated young people. As hypothesize, an
      increasing number of opposite-sex young people was listed as a function of grade
      level. Most nonrelated young people listed (a loose definition of peers) were
      from the same grade, same school, and same neighborhood as the respondent. The
      authors conclude that age-segregation in this community is not extreme (over 40%
      of the significant others listed were adults) and that the Social Relations
      Questionnaire provides a useful and holistic description of an adolescent's
      social world. 

PMID- 24310957
TI  - Escaping loneliness in adolescence: The case for androgyny.
AB  - The purpose of the present study was to assess the relationship between sex-role
      orientation and loneliness in adolescence. Two hundred and twenty-five junior and
      senior high school students completed the Bem Sex Role Inventory Short Form (Bem,
      1981) and the UCLA Loneliness Scale (Russell et al., 1978). Results indicated
      that androgynous individuals were significantly less lonely than masculine,
      feminine, and undifferentiated individuals. An assessment of the independent
      contributions of masculinity and femininity indicated that both masculinity and
      femininity significantly predicted loneliness. Additional analysis revealed that
      the impact of sex-role orientation on loneliness varied by sex and tended to be
      greater for males than females. The need to further examine the relationship
      between androgyny, sex-role development, and adjustment in adolescence is
      discussed. 

PMID- 24310958
TI  - The relation of ego development to sex-stereotyping in caretakers' expectations
      for adolescents.
AB  - The investigators tested the hypothesis that the direction of the relationship
      between the level of ego development of adult caretakers and the degree of sex
      stereotyping in their expectations for adolescents would vary as a function of
      the adolescents' level of ego maturity. Two groups of caretakers (counselors of
      an "immature group" of disturbed adolescents and parents of a "mature group" of
      undergraduates) participated in the study. In comparison to their conformist
      counterparts, the postconformist counselors were expected to make more sex
      stereotyped goals for the disturbed adolescents; postconformist parents were
      expected to make less sex-stereotyped goals for the undergraduates. Hypotheses
      were confirmed for the counselors, but not for the parents. Both groups of
      caretakers seemed to consider developmental or life task factors in formulating
      goals for adolescents. 

PMID- 24310959
TI  - Gender differences in adolescent interpersonal identity formation.
AB  - Gender differences in adolescent interpersonal identity formation were
      investigated in 41 male and 42 female high school juniors and seniors. Subjects
      were interviewed and assessed on progress toward interpersonal identity
      achievement in friendship and dating relationships. Differential patterns of
      correlation for each sex were examined for measures of vocational identity,
      psychological masculinity and femininity, and achievement motivation. Results
      indicated that young women were significantly more identity achieved than men in
      the friendship domain; no differences emerged in the dating domain. The processes
      of interpersonal and vocational identity formation appeared to be more
      interrelated for females than males. For both young men and women, expressive
      attributes of psychological femininity were positively related to interpersonal
      identity exploration. Different gender achievement orientations were revealed by
      positive correlations between several interpersonal identity ratings and mastery
      for males and lack of correlation between interpersonal identity and mastery for
      females. In addition, commitment to a conception regarding friendships was
      positively correlated with competitiveness for males and negatively correlated
      with competitiveness for females. Results are discussed in terms of Gilligan's
      (1982) theoretical work, which contrasts achievement of identity through
      separateness and autonomy with achievement of identity through connectedness and
      relationships. 

PMID- 24310960
TI  - Efficacy of psychiatric inpatient hospitalization for adolescents as measured by
      pre- and post-MMPI profiles.
AB  - The efficacy of inpatient hospitalization on emotionally impaired adolescents was
      investigated using present and past MMPI data. The results indicated that there
      is a "flattening of the profile toward normalcy" from time of admission to
      discharge time. Further statistical analysis revealed that of the 9 clinical MMPI
      scales, the "Depression" scale showed greatest change toward improvement. 

PMID- 24310961
TI  - WISC-R Verbal Performance IQ discrepancies among quay-classified adolescent male
      delinquents.
AB  - Wechsler Verbal-Performance IQ discrepancies have been associated with the broad
      classification of delinquency, but not with a specific criterion of acting out or
      psychopathic adjustment. Accordingly, this study examined the hypothesis that the
      WISC- R Verbal-Performance IQ discrepancy would be larger or more frequent for
      persons classified as exhibiting a psychopathic delinquent adjustment than for
      persons classified as either neurotic or subculturally delinquent. Within-subject
      differences on intellectual measures were obtained for both the psychopathic and
      subcultural, but not the neurotic, delinquent adjustment classification. This
      result indicated consistency of intellectual asymmetry across behaviorally
      diverse delinquent subgroups. No between-group differences were obtained. The
      results were interpreted as affirming a reliable intraindividual intellectual
      asymmetry which provides a foundation to model and test hypotheses relating
      intellectual processes and delinquent behavior. 

PMID- 24310962
TI  - The biosynthesis of cytokinins in crown-gall tissue of Vinca rosea.
AB  - The crown-gall tissue of Vinca rosea converts labelled adenine into cytokinins.
      The principal initial products appear to be ribosylzeatin phosphates; zeatin and
      ribosylzeatin are also produced in appreciable quantities. The efficiency of
      conversion of adenine into cytokinins suggests a pathway of synthesis independent
      of turnover of tRNA. Isopentenyl adenine or its derivatives do not appear to be
      intermediates in the conversion of adenine to zeatin compounds. Cytokinins in V.
      rosea turnover rapidly and further metabolism of zeatin derivatives seems to
      result in their conversion into glucosides which are the main cytokinin active
      compounds in the tissue. 

PMID- 24310963
TI  - A non-aqueous method for the sub-cellular fractionation of cotyledons from
      dormant seeds of Phaseolus vulgaris L.
AB  - A method is described for the sub-cellular ractionation of cotyledons from non
      germinated Phaseolus vulgaris seeds in non-aqueous density gradients of potassium
      iodide in glycerol. The major organelles (protein bodies, cell walls and starch
      grains) are well resolved as adjudged by morphology and protein subunit patterns
      of gradient zones and are remarkably stable if water is rigorously excluded. The
      flexibility of the system is exploited in establishing the cytoplasmic location
      of the oligosaccharide fraction and in the large-scale preparative isolation of
      the sub-cellular components. The composition and morphology of the sub-cellular
      components are described and discussed. 

PMID- 24310964
TI  - Proteolysis in the axis of the germinating pea seed : I. Changes in protein
      degrading enzyme activities of the radicle and primary root.
AB  - Autoproteolytic, caseolytic and haemoglobin degrading activities,
      carboxypeptidase and aminopeptidase activities have all been measured in extracts
      prepared from the radicle of germinating pea seeds (Pisum sativum L.). With
      increasing time from the beginning of imbibition, the spectrum of protein
      degrading enzyme activities changed in a complex manner. As a proportion of total
      autoproteolytic activity, acid proteinases declined, while sulphydryl-and serine
      active site endopeptidases accounted for increased proportions of the total
      activity. The distribution of protein degrading enzyme activities in the root tip
      compared with the balance of the root was determined after 4 days, at the onset
      of cell division in the root apex. On a fresh weight basis the tip was enriched
      ca. 2-fold in protein concentration and all of the exopeptidases. Autoproteolytic
      activity was concentrated in the tip to a lesser degree, and haemoglobin
      degrading activity not at all. In contrast, the root tip was depleted in
      caseolytic activity. 

PMID- 24310965
TI  - Proteolysis in the axis of the germinating pea seed : II. Changes in polypeptide
      composition.
AB  - The radicle of the pea embryo (Pisum sativum L.) is known to possess a range of
      protein-degrading enzymes which could theoretically act in vivo to break down
      proteins stored in the radicle. However, most of the polypeptides of the radicle
      showed little evidence of net breakdown in vivo in the first 4 days from
      imbibition. One polypeptide, of mol. mass 13,000, was degraded almost completely
      between 1 and 2 days from imbibition; others, of mol. mass 84,000 and 30,000 were
      degraded within 4 days. The breakdown of polypeptides stored in the radicle (and
      plumule) is thus highly selective and closely regulated. The requirement for
      amino nitrogen in the growing axis is evidently met by the immediate export of
      amino acids from the cotyledons, rather than by massive breakdown of stored
      polypeptides in situ. 

PMID- 24310966
TI  - Influence of bovine serum albumine on the proton conductance of potato
      mitochondria membranes.
AB  - Pulsed acid base titrations, according to the procedure of Mitchell and Moyle,
      have been carried out on potato mitochondria in the presence and absence of
      Bovine Serum Albumine (BSA). The rate of the pH decay is slower when BSA is
      present. The buffering capacities of the outer and inner phases, the t1/2 of the
      pH decay after an acid pulse and the proton conductance of the inner membrane
      have been measured. The results show that plant mitochondria are relatively
      impermeable to H(+) and OH(-), but leakier than animal mitochondria. This may be
      related to the lower respiratory control ratios generally found with plant
      mitochondria. 

PMID- 24310967
TI  - Quenching of the fluorescence emitted by P695-682 at room temperature in
      etiolated illuminated leaves.
AB  - Chlorophyll(ide) fluorescence emission decreases at room temperature during
      completion of protochlorophyll(ide) reduction. The process responsible for this
      quenching is parallel to the P688-676 ->P695-682 transition. It proceeds equally
      well in darkness and in the light. It consists in a decrease of the fluorescence
      yield of chlorophyll(ide) in P695-682. Apparently, room temperature P695-682
      fluorescence is regulated by a conjunction of factors such as energy transfers
      and photobiochemical activities. 

PMID- 24310968
TI  - Localization of gibberellic acid-induced acid phosphatase activity in the
      endoplasmic reticulum of barley aleurone cells with the electron microscope.
AB  - A metal-salt precipitation method with p-nitrophenyl phosphate as substrate has
      been used to localize in the electron microscope acid phosphatase activity in
      isolated aleurone layers of barley (Hordeum vulgare L.), treated for 16 h in the
      presence or absence of gibberellic acid (GA3). The paper confirms results
      obtained earlier with an azo-dye precipitation method of enzyme localization. In
      addition the results show for the first time that in GA3-treated tissue enzyme
      activity is associated with the endoplasmic reticulum (ER), there being reaction
      product deposited in the ER cisternae. It is suggested that this activity
      represents new enzyme synthesized on ER in response to GA3 and probably destined
      for secretion. 

PMID- 24310969
TI  - Oxygen and carbon dioxide exchanges in crassulacean-acid-metabolism-plants.
AB  - The 24 h O2 uptake and release together with the CO2 balance have been measured
      in two CAM plants, one a non-succulent Sempervivum grandifolium, the other a
      succulent Prenia sladeniana. The O2 uptake was estimated by the use of (18)O2. It
      was found that the mean hourly O2 uptake in the light was 7 times that in the
      dark for Sempervivum and 5 times that for Prenia, after correction for the
      lightdark temperature difference. It was estimated that oxygen uptake in the
      light was 2.4 times greater than oxygen release (=net photosynthesis) in
      Sempervivum and 1.4 times greater in Prenia. In both plants there was a positive
      carbon balance over the 24 h period under the experimental conditions. It was
      estimated that malate formed during the night could, if completely oxidized to
      CO2 and water, account for 74% of the light phase O2 uptake in Sempervivum. In
      Prenia the O2 uptake was more than sufficient to account for a full oxidation of
      malate. 

PMID- 24310970
TI  - A dual role for the endosperm and its galactomannan reserves in the germinative
      physiology of fenugreek (Trigonella foenum-graecum L.), an endospermic leguminous
      seed.
AB  - Some 30% of the reserve material in the fenugreek seed is galactomannan localised
      in the endosperm; the remainder is mainly protein and lipid in the cotyledons of
      the embryo. The importance of galactomannan to the germinative physiology of
      fenugreek has been investigated by comparing intact and endosperm-free seeds.
      From a purely nutritional point of view the galactomannan's role is not
      qualitatively different from that of the food reserves in the embryo.
      Nevertheless, due to its spatial location and its hydrophilic properties, the
      galactomannan is the molecular basis of a mechanism whereby the endosperm imbibes
      a large quantity of water during seed hydration and is able to "buffer" the
      germinating embryo against desiccation during subsequent periods of drought
      stress. The galactomannan is clearly a dual-purpose polysaccharide, regulating
      water-balance during germination and serving as a substrate reserve for the
      developing seedling following germination. The relative importance of these two
      roles is discussed. 

PMID- 24310971
TI  - Kinetin-promoted transport of assimilates in stems of Phaseolus vulgaris L. :
      Localized versus remote site(s) of action.
AB  - Kinetin, applied as a dispersion in aqueous lanolin to the stumps of decapitated
      stems of P. vulgaris plants with their roots removed, was found to promote the
      transport of (14)C- and (32)P-labelled assimilates to the site of hormone
      application. Measurement of photosynthetic rate of, and assimilate export rate
      from the source leaves, indicated that kinetin was not acting to promote
      assimilate transport by stimulating these processes. Moreover, it was found that
      the time between kinetin application and detection of an enhanced transport flux
      was independent of the distance over which kinetin would need to move to be
      present throughout the length of the transport pathway. These observations,
      together with the finding that lateral applications of kinetin to the stems
      resulted in an enhanced localized accumulation of assimilates, provided evidence
      that kinetin acted locally at its point of application to stimulate assimilate
      transfer. 

PMID- 24310972
TI  - The frequency of embryogenic pollen grains is not increased by in vitro anther
      culture in Nicotiana tabacum L.
AB  - The numbers of embryogenic (S) grains present in in-situ mature anthers of
      Nicotiana tabacum L. were compared to the numbers of embryos and plantlets
      produced in cultured anthers excised at the optimal mitotic stage of development
      for anther culture. The Feulgen technique of staining embryos caused a
      considerable loss of grains from cultured anthers but this did not seriously
      affect the determination of the percentage of embryos present. In no instance did
      the numbers of embryos produced exceed the maximum number of S grains found, and
      the distributions of S grain and embryo frequencies in anthers were similar. In
      rare instances S grains which had undergone the first embryogenic division were
      observed in situ. The results indicate that all grains capable of embryogenesis
      are determined during early flower formation and that their number is not
      increased by in vitro culture. 

PMID- 24310973
TI  - Characteristics of the sucrose uptake system of vacuoles isolated from red beet
      tissue. Kinetics and specifity of the sucrose uptake system.
AB  - The uptake of sucrose against a concentration gradient into the dextran
      impermeable [(3)H]H2O space of red beet (Beta vulgaris L.) vacuoles has been
      studied using silicone-layer-filtering centrifugation on both fluorometric and
      (14)C-measurement of sucrose. Sucrose transport into vacuoles proceeds partly by
      an active transport system and partly by passive permeation. The K M(20 degrees
      C) for active sucrose uptake was found to be about 22 mM and the V Max(20 degrees
      C) was about 174 nmol sucrose x (unit betacyanin)(-1) x h(-1). The temperature
      dependency of sucrose transport appears to have an activation energy of 35,0
      KJ*mol(-1). Among various mono-, di-, and trisaccharides tested, raffinose acts
      as a competitive inhibitor of sucrose uptake. 

PMID- 24310974
TI  - Interactions between parallel pathways during biosynthesis of rosmarinic acid in
      cell suspension cultures of Coleus blumei.
AB  - Phenylalanine ammonia-lyase from an "over-producer" strain of Coleus blumei
      Benth. cell cultures accumulating high levels of rosmarinic acid (RA) has been
      shown to possess no special feed-back sensitivity to RA or its precursors. No
      tyrosine-3-hydroxylase activity could be detected in culture extracts and no
      specific inhibitors of tyrosine incorporation into RA were found. L-alpha
      aminooxy-beta-phenyl propionic acid, however, was effective in specifically
      blocking phenylalanine incorporation. This block also led to an accumulation of
      label from tyrosine in 4-hydroxyphenyllactic acid rather than in 3,4
      dihydroxyphenylalanine (DOPA) or 3,4-dihydroxyphenyllactic acid. These
      observations require a re-evaluation of the possible role of DOPA as a major
      biogenic precursor to RA. 

PMID- 24310975
TI  - Identification by combined gas chromatography-mass spectrometry of phaseic acid
      and dihydrophaseic acid and characterization of further abscisic acid metabolites
      in pea seedlings.
AB  - Seven day old seedlings of Pisum sativum L., cv. Kleine Rheinlanderin, were
      wilted for 3 days. After partially removing the roots, they were rewatered and at
      the same time radioactive abscisic acid([1-(14)C]ABA, spec. activity 1.7.10(8)d
      s(-1)mmol(-1)) was applied for 1 h via the xylem of the roots. After 24 h, 4
      days, and 12 days the seedlings were extracted and the metabolites of ABA were
      analyzed by means of thin-layer and gas chromatography in combination with mass
      spectrometry, autoradiography, and scintillation counting. Phaseic acid (PA) and
      dihydrophaseic acid (DPA) were identified as metabolites of ABA. The presence of
      another ABA-metabolite was also demonstrated. From its mass spectrum it has been
      postulated that this metabolite is 4'-desoxy-ABA. In addition to these
      substances, several other metabolites, which are more polar than ABA and its
      known degradation products, were present in the seedlings. The quantity and
      number of these unknown metabolites increased with time. 

PMID- 24310976
TI  - Preparation of protoplasts from the green alga Enteromorpha intestinalis (L.)
      Link.
AB  - Protoplasts have been obtained from vegetative thallus of the green seaweed
      Enteromorpha following enzymic digestion with driselase and pectinase. The
      viability of purified protoplast fractions was assessed by staining and
      measurements of O2 uptake and evolution. 

PMID- 24310978
TI  - Erratum.

PMID- 24310977
TI  - Conjoined mitochondria and plastids in the barley mutant 'albostrians'.
AB  - The intercalary meristem and surrounding tissues of the gene induced plastome
      mutant 'albostrians' of Hordeum vulgare L. were examined in the electron
      microscope for ultrastructural evidence of membrane continuities between plastids
      and mitochondria. In well developed tissues the ribosome-deficient plastids were
      usually in close proximity or appressed to mitochondria of normal appearance. In
      some sections through the meristemmatic region however the relationship between
      the two organelles was observed to be of a fused nature. These conjoinings are
      thought to be similar to those reported in normal living cells using
      cinephotomicrography but never before observed by transmission electron
      microscopy. 

PMID- 24310979
TI  - Binding of ascorbic acid and alpha-tocopherol to bovine serum albumin: a
      comparative study.
AB  - Binding of ascorbic acid (water-soluble antioxidant) and alpha-tocopherol (lipid
      soluble antioxidant) to bovine serum albumin (BSA) has been studied using
      isothermal titration calorimetry (ITC), in combination with fluorescence
      spectroscopy, UV-vis absorption spectroscopy and Fourier transform infrared (FT
      IR) spectroscopy. Thermodynamic investigations reveal that ascorbic acid/alpha
      tocopherol binding to BSA is driven by favorable enthalpy and unfavorable
      entropy, and the major driving forces are hydrogen bonding and van der Waals
      forces. For ascorbic acid, the interaction is characterized by a high number of
      binding sites, which suggests that binding occurs by a surface adsorption
      mechanism that leads to coating of the protein surface. For alpha-tocopherol, one
      molecule of alpha-tocopherol combines with one molecule of BSA and no more alpha
      tocopherol binding to BSA occurs at concentration ranges used in this study.
      Fluorescence experiments suggest that ascorbic acid has predominantly a "sphere
      of action" quenching mechanism, whereas, for alpha-tocopherol, the quenching
      mechanism is "static quenching" and due to the formation of a ground state
      complex. Additionally, as shown by the UV-vis absorption, synchronous
      fluorescence spectroscopy, and FT-IR, ascorbic acid and alpha-tocopherol may
      induce conformational and microenvironmental changes of BSA. 

PMID- 24310980
TI  - Phellinus tropicalis abscesses in a patient with chronic granulomatous disease.
AB  - Chronic Granulomatous Disease (CGD), caused by genetic defects in components of
      the phagocyte NADPH oxidase pathway, leads to recurrent life-threatening
      bacterial and invasive fungal infections. While a number of unique pathogens have
      been associated with this disease, the causative organisms may be difficult to
      identify. Here, we present a 24 year old male with known X-linked CGD who
      concurrently developed a cervical abscess and an abscess in the subcutaneous
      tissues of the right hip, both of which were surgically drained. Cultures failed
      to identify any organisms. He was treated empirically with ertapenem but the hip
      abscess recurred at the original site and in contiguous dependent areas in the
      posterior thigh and knee. A filamentous organism was observed microscopically,
      initially considered a contaminant, but on culture yielded a mold growth,
      identified as Phellinus tropicalis (synonym: Inonotus tropicalis) based on
      phenotypic and molecular methods. This is the third case report of human
      infection with P. tropicalis, all in subjects with CGD. The patient was treated
      with voriconazole with resolution of his symptoms.

PMID- 24310981
TI  - Leaf chemistry as a predictor of primate biomass and the mediating role of food
      selection: a case study in a folivorous lemur (Propithecus verreauxi).
AB  - Folivorous primate biomass has been shown to positively correlate with the
      average protein-to-fiber ratio in mature leaves of tropical forests. However,
      studies have failed to explain the mismatch between dietary selection and the
      role of the protein-to-fiber ratio on primate biomass; why do not folivores
      always favor mature leaves or leaves with the highest protein-to-fiber ratio? We
      examined the effect of leaf chemical characteristics and plant abundance (using
      transect censuses; 0.37 ha, 233 trees) on food choices and nutrient/toxin
      consumption in a folivorous lemur (Propithecus verreauxi) in a gallery forest in
      southern Madagascar. To assess the nutritional quality of the habitat, we
      calculated an abundance-weighted chemical index for each chemical variable. Food
      intake was quantified using a continuous count of mouthfuls during individual
      full-day follows across three seasons. We found a significant positive
      correlation between food ranking in the diet and plant abundance. The protein-to
      fiber ratio and most other chemical variables tested had no statistical effect on
      dietary selection. Numerous chemical characteristics of the sifaka's diet were
      essentially by-products of generalist feeding and "low energy input/low energy
      crop" strategy. The examination of feeding behavior and plant chemistry in Old
      World colobines and folivorous prosimians in Madagascar suggests that relative
      lack of feeding selectivity and high primate biomass occur when the average
      protein-to-fiber ratio of mature leaves in the habitat exceeds a threshold at
      0.4.

PMID- 24310982
TI  - Investigation of tDCS volume conduction effects in a highly realistic head model.
AB  - OBJECTIVE: We investigate volume conduction effects in transcranial direct
      current stimulation (tDCS) and present a guideline for efficient and yet accurate
      volume conductor modeling in tDCS using our newly-developed finite element (FE)
      approach. APPROACH: We developed a new, accurate and fast isoparametric FE
      approach for high-resolution geometry-adapted hexahedral meshes and tissue
      anisotropy. To attain a deeper insight into tDCS, we performed computer
      simulations, starting with a homogenized three-compartment head model and
      extending this step by step to a six-compartment anisotropic model. MAIN RESULTS:
      We are able to demonstrate important tDCS effects. First, we find channeling
      effects of the skin, the skull spongiosa and the cerebrospinal fluid
      compartments. Second, current vectors tend to be oriented towards the closest
      higher conducting region. Third, anisotropic WM conductivity causes current flow
      in directions more parallel to the WM fiber tracts. Fourth, the highest cortical
      current magnitudes are not only found close to the stimulation sites. Fifth, the
      median brain current density decreases with increasing distance from the
      electrodes. SIGNIFICANCE: Our results allow us to formulate a guideline for
      volume conductor modeling in tDCS. We recommend to accurately model the major
      tissues between the stimulating electrodes and the target areas, while for
      efficient yet accurate modeling, an exact representation of other tissues is less
      important. Because for the low-frequency regime in electrophysiology the quasi
      static approach is justified, our results should also be valid for at least low
      frequency (e.g., below 100 Hz) transcranial alternating current stimulation.

PMID- 24310983
TI  - Synthesis of the C(18) -norditerpenoid alkaloid neofinaconitine: a lesson in
      convergent synthesis planning.
AB  - Hexacyclic framework: The total synthesis of the complex C18 -norditerpenoid
      alkaloid neofinaconitine has been achieved by a convergent approach. This
      remarkable synthesis featured two Diels-Alder cycloadditions and subsequent
      Mannich-type N-acyliminium and radical cyclizations to establish the unique
      hexacyclic core structure of the target molecule. 

PMID- 24310984
TI  - Methylomics analysis identifies epigenetically silenced genes and implies an
      activation of beta-catenin signaling in cervical cancer.
AB  - Using DNA methylation biomarkers in cancer detection is a potential direction in
      clinical testing. Some methylated genes have been proposed for cervical cancer
      detection; however, more reliable methylation markers are needed. To identify new
      hypermethylated genes in the discovery phase, we compared the methylome between a
      pool of DNA from normal cervical epithelium (n = 19) and a pool of DNA from
      cervical cancer tissues (n = 38) using a methylation bead array. We integrated
      the differentially methylated genes with public gene expression databases, which
      resulted in 91 candidate genes. Based on gene expression after demethylation
      treatment in cell lines, we confirmed 61 genes for further validation. In the
      validation phase, quantitative MSP and bisulfite pyrosequencing were used to
      examine their methylation level in an independent set of clinical samples.
      Fourteen genes, including ADRA1D, AJAP1, COL6A2, EDN3, EPO, HS3ST2, MAGI2,
      POU4F3, PTGDR, SOX8, SOX17, ST6GAL2, SYT9, and ZNF614, were significantly
      hypermethylated in CIN3+ lesions. The sensitivity, specificity, and accuracy of
      POU4F3 for detecting CIN3+ lesions were 0.88, 0.82, and 0.85, respectively. A
      bioinformatics function analysis revealed that AJAP1, EDN3, EPO, MAGI2, and SOX17
      were potentially implicated in beta-catenin signaling, suggesting the epigenetic
      dysregulation of this signaling pathway during cervical cancer development. The
      concurrent methylation of multiple genes in cancers and in subsets of
      precancerous lesions suggests the presence of a driver of methylation phenotype
      in cervical carcinogenesis. Further validation of these new genes as biomarkers
      for cervical cancer screening in a larger population-based study is warranted. 

PMID- 24310985
TI  - LIM homeobox transcription factor 1B is associated with pro-fibrotic components
      and apoptosis in hypoxia/reoxygenation renal tubular epithelial cells.
AB  - LIM homeobox transcription factor 1B (LMX1B) is a transcription factor of the LIM
      homeodomain type, which plays an important role in foetal development during
      formation of the extremities, kidneys, eyes, and the brain. Furthermore, LMX1B
      has been implicated in nail-patella syndrome, which is predominantly
      characterized by malformation of limbs and nails, and in 30 % of patients,
      nephropathy, including renal fibrosis, is observed. Since no reports were
      available that studied the link between LMX1B expression and pro-fibrotic
      components and apoptosis in hypoxic renal tubular epithelial cells (RTEC), we
      explored if LMX1B was associated with extracellular matrix components,
      profibrotic factors, and apoptosis induced by hypoxia/reoxygenation (H-R). In
      this cell system under hypoxic conditions, when the expression of LMX1B was
      inhibited in H-R RTEC, the expression of transforming growth factor-betal,
      collagen-III, fibronectin, cleaved caspase-3, and cell apoptosis rate was
      increased. Consequently, overexpression of LMX1B was associated with reduced cell
      apoptosis, whilst downregulation of LMX1B was associated with increased cell
      apoptosis in H-R RTEC. 

PMID- 24310986
TI  - Exploring the repetition paradox: the effects of learning context and massed
      repetition on memory.
AB  - Although repetition is generally assumed to enhance the accessibility of memory
      for rehearsed material, recent research has suggested that prolonged repetition
      might actually be detrimental under some conditions. In the present work, we
      manipulated repetition duration and learning condition (intentional vs.
      incidental) in an effort to clarify the relationship between repetition and
      memory. Replicating previous findings, memory for repeated items declined with
      increased repetition under incidental-learning conditions. However, increased
      repetition had the opposite effect under intentional-learning conditions. Taken
      together, these results provide evidence for distinctive mechanisms of memory
      acquisition during repetition that vary depending on learning context. 

PMID- 24310987
TI  - The value of vaginal packing in pelvic floor surgery: a randomised double-blind
      study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to evaluate the
      effect of vaginal packing following pelvic floor surgery with regard to post
      operative pain, bleeding and infection. This was a double-blind randomised study
      of women undergoing vaginal hysterectomy and/or pelvic floor repair at a tertiary
      urogynaecology unit. METHODS: The primary outcome of day 1 post-operative pain
      was assessed using the short-form McGill Pain score. Secondary outcomes were
      haematological and infective morbidity, evaluated using changes in full blood
      count, and cultures of midstream urine and high vaginal swabs. A transvaginal
      ultrasound scan to exclude pelvic haematoma was performed at 6 weeks in all women
      who underwent vaginal hysterectomy with or without a pelvic floor repair.
      RESULTS: In total, 190 women were recruited: mean age 58.3 years (27-91 years),
      mean body mass index 27.4 kg/m(2) and median parity 3. Women were randomised into
      the 'pack' (n = 86) and 'no pack' (n = 87) arms with no demographic differences
      between the groups. No statistically significant differences in the post
      operative pain scores or secondary outcome measures were demonstrated. Incidence
      of haematoma formation (14.8 % no pack, 7.3 % pack, p = 0.204) was not
      statistically significant. There were three clinically significant complications
      in the no pack group and none in the pack group. CONCLUSIONS: This is the first
      study to examine pain in association with post-operative vaginal packing. There
      is no evidence to suggest that packing increases pain scores or post-operative
      morbidity. A trend towards increased haematoma and significant complications was
      seen in the no pack group. As vaginal packing does no harm and may be of some
      benefit it may be argued that packing should be recommended as routine clinical
      practice.

PMID- 24310988
TI  - Perceptions about female urinary incontinence: a systematic review.
AB  - INTRODUCTION AND HYPOTHESIS: Perceptions about urinary incontinence (UI) may have
      a differential impact on treatment-seeking behaviors. Thus, we aimed to
      systematically review perceptions regarding UI in women of different racial and
      ethnic populations. METHODS: MEDLINE, EMBASE, Scirus, Google Scholar, Open J
      Gate, AgeLine, and Global Health (CABI) were searched from January 1980 to August
      2011. We included qualitative studies that described knowledge, perception, or
      personal views about UI in women. Studies were excluded if they did not specify
      race/ethnicity of subjects, if they reported on non-UI urinary symptoms, or if
      they were performed exclusively in men. Three independent reviewers screened all
      studies. The relevance, appropriateness, transparency, and soundness (RATS) scale
      for qualitative research was used to assess study quality. Because of the
      qualitative data, meta-analyses were not performed. RESULTS: Of 3,676 citations,
      23 studies met the inclusion criteria. Based on the RATS scale, these were
      categorized into 11 high-, 2 moderate-, and 10 low-quality studies. Dominant
      themes fell into two categories, UI management and UI experience, and were
      similar across racial/ethnic groups. Across multiple studies, women reiterated a
      preference for discussing UI with other women, even if this was not a physician.
      Non-white women expressed self-blame and perceived UI as a negative outcome from
      childbirth or prior sexual experiences. Latina women maintained more secrecy
      around this issue, even amongst family members. CONCLUSIONS: Women across
      different racial and ethnic groups share similar UI management strategies and UI
      experiences. However, perceptions about UI may differ in certain populations.
      These findings could be useful when considering future educational strategies
      regarding UI in women.

PMID- 24310989
TI  - 3D pelvic floor ultrasound findings and severity of anal incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of our study was to determine the
      association between the severity of anal incontinence and levator ani deficiency,
      anal sphincter defects, anorectal angle, and colonic motility abnormalities.
      METHODS: This was a retrospective study. Subjects were categorized into three
      groups: normal, minor anal incontinence, and major anal incontinence according to
      their answers to the PFDI-20 questionnaire. 3D endovaginal ultrasound was
      utilized to assess levator ani muscle and the anorectal angle. Levator ani muscle
      subdivisions were scored based on avulsion from the pubic bone and muscle
      thickness, based on our previous work. 3D endoanal ultrasound was utilized to
      assess anal sphincters. Colonic motility abnormalities were defined as diarrhea,
      constipation or both. RESULTS: Ninety-seven patients were included in the
      analysis: 45 with major anal incontinence, 29 with minor anal incontinence, and
      23 continent women. On multivariate logistic regression, sphincter defect,
      anorectal angle, and colonic motility abnormalities were associated with anal
      incontinence severity. Women with an external anal sphincter defect had a 20.36
      fold chance of having severe anal incontinence compared with patients with no
      defect (OR 20.36, 95% CI 5.4, 76.6); those with both defective sphincters had a
      102.5-fold chance of having severe anal incontinence (OR 102.5, 95% CI 10.2,
      >999). Anorectal angle >=170 degrees  was significantly associated with the
      severity of anal incontinence (OR = 4.07, 95% CI 1.53, 10.79), as was the
      presence of colonic mobility abnormality (OR 5.31, 95% CI 1.86, 15.19).
      CONCLUSIONS: 3D pelvic floor ultrasound can be an efficient tool for anal
      incontinence evaluation in women. Anal sphincter defects, colonic motility
      abnormalities, and anorectal angle were associated with the severity of anal
      incontinence. While there was a trend toward worsening levator ani deficiency
      among those with major anal incontinence, this did not reach statistical
      significance.

PMID- 24310990
TI  - Does fibromyalgia influence symptom bother from pelvic organ prolapse?
AB  - INTRODUCTION AND HYPOTHESIS: Determine if women with fibromyalgia report
      increased bother from pelvic organ prolapse compared with women without
      fibromyalgia. METHODS: We performed a cross-sectional study of women with
      symptomatic prolapse on consultation with a private urogynecology practice within
      a 46-month period. After matching for age, women with a diagnosis of fibromyalgia
      were compared with a reference group of women without fibromyalgia. Demographic,
      POPQ examination, medical history, and pelvic floor symptom data (PFDI, PFIQ, and
      PISQ-12) were collected. Our primary outcome was to compare the mean Pelvic Floor
      Distress Inventory (PFDI) scores of women with and without fibromyalgia. RESULTS:
      The prevalence of fibromyalgia in women evaluated for initial urogynecology
      consultation during the study period was 114 out of 1,113 (7%). Women with
      fibromyalgia reported significantly higher symptom bother scores related to
      pelvic organ prolapse, defecatory dysfunction, urinary symptoms, and sexual
      function: PFDI (p = 0.005), PFIQ (p=0.010), and PISQ (p=0.018). Women with
      fibromyalgia were found to have a higher BMI (p=0.008) and were more likely to
      report a history of sexual abuse, OR 3.1 (95 % CI 1.3, 7.9), and have levator
      myalgia on examination, OR 3.8 (95% CI 1.5, 9.1). In a linear regression
      analysis, levator myalgia was found to be the significant factor associated with
      pelvic floor symptom bother. CONCLUSIONS: In women with symptomatic prolapse,
      fibromyalgia is associated with an increased risk of levator myalgia and 50% more
      symptom bother from pelvic floor disorders.

PMID- 24310991
TI  - Review of 1934 paper Rex v Donellan.

PMID- 24310992
TI  - The future of criminal legal aid.

PMID- 24310993
TI  - Lessons from Stafford.
AB  - A Public Inquiry into deficiencies at an acute hospital trust revealed not only
      many experiences of appalling care suffered by patients. Although it had been
      claimed that there were no warning signs of the poor state of affairs prevalent
      at the trust the Inquiry found evidence that staff, whistle-blowers and external
      bodies had been raising concerns the impact on patients of which were ignored or
      insufficiently understood. Mortality data was not accepted as showing a need to
      review standards of care. There was found to be a negative culture focussed on
      doing the system's business not that of the patients. Suggestions are made as to
      what trust boards should do to avoid similar issues arising in the future. 

PMID- 24310994
TI  - The Medico-Legal Society dinner 2013.

PMID- 24310995
TI  - An analysis of blogs from medical students on "English Parallel" courses in
      Central and Eastern Europe.
AB  - During the last 20 years, there has been a significant growth in the training of
      overseas students especially within the European Union. Informal discussions with
      past and present students revealed a marked reluctance to take part in interviews
      about the nature of "English Parallel" courses. Alternative sources of
      information include blogs and commentaries written on the internet by present and
      former students at these schools. Such blogs are relatively limited in number and
      of variable length. They have been written for a variety of reasons and range in
      content from commentaries on training to wider discussion of life in Central and
      Eastern Europe. Six blogs were identified from an internet search, and a
      qualitative approach was adopted for the analysis of text content. Their
      experience is assessed, and potential approaches to greater integration of
      training across Europe are considered. 

PMID- 24310996
TI  - Dynamic approaches to the mechanism of photosynthesis.
AB  - An account of the author's life and scientific research is presented. Two main
      lines of research have been pursued: (1) Studies on the physiological aspect of
      photosynthesis started from experiments with crops under field conditions and
      then extended to the study of photosynthesis in nature; and (2) studies on the
      mechanism of photophosphorylation and related problems which began with the
      measurement of quantum requirement of photophosphorylation. This work led to the
      discovery of the 'high energy state' of phosphorylation and many other
      interesting findings. In recent years, efforts have been made to study the
      operation and regulation of photosynthetic apparatus with a view to link the
      above-mentioned lines of research together. 

PMID- 24310998
TI  - Identification of a novel light-harvesting complex II protein (LHC IIc').
AB  - The caroteno-chlorophyll-protein, LHC IIc, is a relatively minor component of the
      PS II antenna. Isolated LHC IIc contains a major protein of 28 kDa along with a
      26 kDa subunit in lower abundance. Previously, it was not known if the 26 kDa
      protein was closely related to the 28 kDa LHC IIc protein or if it was a
      comigrating LHC IIb contaminating subunit. A sequence of 20 amino acid residues
      was obtained by direct protein micro-sequencing of an internal cyanogen bromide
      derived peptide fragment of the 26 kDa protein isolated from barley. The sequence
      shows, and antibody reactions confirm, that the 26 kDa protein is similar but
      distinct from both the 28 kDa LHC IIc and LHC IIb protein sequences, indicating
      that there remains at least one more cab gene to be identified in higher plants.
      Furthermore, it is difficult to interpret the data in any way other than that
      there is a novel LHC II pigment-protein (LHC IIc') that co-migrates with LHC IIc.

PMID- 24310997
TI  - Biogenesis of thylakoid membranes with emphasis on the process in Chlamydomonas.
AB  - Recent results obtained by electron microscopic and biochemical analyses of
      greening Chlamydomonas reinhardtii y1 suggest that localized expansion of the
      plastid envelope is involved in thylakoid biogenesis. Kinetic analyses of the
      assembly of light-harvesting complexes and development of photosynthetic function
      when degreened cells of the alga are exposed to light suggest that proteins
      integrate into membrane at the level of the envelope. Current information,
      therefore, supports the earlier conclussion that the chloroplast envelope is a
      major biogenic structure, from which thylakoid membranes emerge. Chloroplast
      development in Chlamydomonas provides unique opportunities to examine in detail
      the biogenesis of thylakoids. 

PMID- 24310999
TI  - Range of photosynthetic control of postillumination P700(+) reduction rate in
      sunflower leaves.
AB  - The kinetics of the postillumination reduction of P700(+) which reflects the rate
      constant for plastoquinol (PQH2) oxidation was recorded in sunflower leaves at
      different photon absorption densities (PAD), CO2 and O2 concentrations. The P700
      oxidation state was calculated from the leaf transmittance at 830 nm logged at 50
      MUs intervals. The P700(+) dark reduction kinetics were fitted with two exponents
      with time constants of 6.5 and about 45 ms at atmospheric CO2 and O2
      concentrations. The time constant of the fast component, which is the major
      contributor to the linear electron transport rate (ETR), did not change over the
      range of PADs of 14.5 to 134 nmol cm(-2) s(-1) in 21% O2, but it increased up to
      40 ms under severe limitation of ETR at low O2 and CO2. The acceptor side of
      Photosystem I (PS I) became reduced in correlation with the downregulation of the
      PQH2 oxidation rate constant. It is concluded that thylakoid pH-related
      downregulation of the PQH2 oxidation rate constant (photosynthetic control) is
      not present under normal atmospheric conditions but appears under severe
      limitation of the availability of electron acceptors. The measured range of
      photosynthetic control fits with the maximum variation of ETR under natural
      stress in C3 plants. Increasing the carboxylase/oxygenase specificity would lead
      to higher reduction of the PS I acceptor side under stress. 

PMID- 24311000
TI  - Favoured carbonyl binding regions around the QA and Q B sites of Rps. viridis.
AB  - The factors governing quinone protein binding in the photosynthetic bacterium
      Rps. viridis are investigated via use of empirical intermolecular energy
      calculations using the GRID method (PJ Goodford (1985) J Med Chem 28: 849-854). A
      probe atom corresponding to a carbonyl oxygen atom is used to investigate regions
      exhibiting preference for carbonyl binding in the QA and QB sites of Rps.
      viridis. Two distinct regions at the top and bottom of the sites are revealed to
      be most favourable for carbonyl binding. Overlay of the crystallographically
      determined positions for the quinone carbonyl groups shows that they lie within
      the regions predicted theoretically. The method is also shown to be able to give
      qualitative insight into the affect of amino acid mutations of quinone binding. 

PMID- 24311001
TI  - The relationship between millisecond luminescence and fluorescence in tobacco
      leaves during the induction period.
AB  - Millisecond luminescence and fluorescence, from an intact tobacco (Nicotiana
      tabacum) leaf, were measured simultaneously during the induction period, as a
      function of the time. This was accomplished using a luminescence apparatus which
      separated out the faster luminescence components by subtraction of the
      accumulated slow-decaying ones. An antiparallel correlation between the two was
      observed, but only during a part of the induction period starting with the first
      fluorescence peak where the fluorescence decreases to a quasi plateau level.
      During this induction phase, luminescence rose very prominently to a maximum
      while fluorescence decreased. This correlation fits a linear dependence of the
      luminescence on the extent of RCs openness, as monitored by the photochemical
      quenching of the fluorescence. It may be concluded that during this induction
      phase, all other factors, which modulate luminescence (e.g. membrane potential),
      have become already steady and that the millisecond delayed luminescence reflects
      the photochemical reaction in an open center (i.e. with QA oxidized). This is
      further supported by steady-state experiments in thylakoid membranes. No
      correlations between luminescence and either momentary (F) or maximum (Fm)
      fluorescence during later induction phases can be pinpointed with confidence,
      although a trend of a parallel decrease at certain time intervals can be seen
      occasionally. Likewise, there is no relationship between the two in the very
      initial induction phase, during the rise of fluorescence from Fo to Fm, as noted
      earlier. This lack of correlation is presumably due to the dependence of
      luminescence on other parameters, which vary during these induction phases. The
      implications of these observations are discussed. 

PMID- 24311002
TI  - Interaction of analogues of substrate with NADP-malic enzyme from maize leaves.
AB  - The effect of structural analogues of L-malate was studied on NADP-malic enzyme
      purified from Zea mays L. leaves. Among the compounds tested, the organic acids
      behaved as more potent inhibitors at pH 7.0 than at pH 8.0, suggesting that the
      dimeric form was more susceptible to the inhibition than the tetrameric form of
      the enzyme.Oxalate, ketomalonate, hydroxymalonate, malonate, oxaloacetate,
      tartrate, alpha-hydroxybutyrate, alpha-ketobutyrate, alpha-ketoglutarate and
      alpha-hydroxyglutarate exhibited linear competitive inhibition with respect to
      the substrate L-malate at pH 8.0. On the other hand, glyoxylate and glycolate
      turned out to be non-competitive inhibitors, while glycolaldehyde, succinate,
      fumarate, maleate and beta- and gamma-hydroxybutyrate had no effect on the enzyme
      activity, at the concentrations assayed. These results suggest that the extent of
      inhibition was dependent on the size of the analogues and that the presence of an
      1-carboxyl group along with a 2-hydroxyl or 2-keto group was important for
      binding of the substrate analogue to the enzyme. 

PMID- 24311003
TI  - Photosystem II in a mutant of Chlamydomonas reinhardtii lacking the 23 kDa psbP
      protein shows increased sensitivity to photoinhibition in the absence of
      chloride.
AB  - The psbP gene product, the so called 23 kDa extrinsic protein, is involved in
      water oxidation carried out by Photosystem II. However, the protein is not
      absolutely required for water oxidation. Here we have studied Photosystem II
      mediated electron transfer in a mutant of Chlamydomonas reinhardtii, the FUD 39
      mutant, that lacks the psbP protein. When grown in dim light the Photosystem II
      content in thylakoid membranes of FUD 39 is approximately similar to that in the
      wild-type. The oxygen evolution is dependent on the presence of chloride as a
      cofactor, which activates the water oxidation with a dissociation constant of
      about 4 mM. In the mutant, the oxygen evolution is very sensitive to
      photoinhibition when assayed at low chloride concentrations while chloride
      protects against photoinhibition with a dissociation constant of about 5 mM. The
      photoinhibition is irreversible as oxygen evolution cannot be restored by the
      addition of chloride to inhibited samples. In addition the inhibition seems to be
      targeted primarily to the Mn-cluster in Photosystem II as the electron transfer
      through the remaining part of Photosystem II is photoinhibited with slower
      kinetics. Thus, this mutant provides an experimental system in which effects of
      photoinhibition induced by lesions at the donor side of Photosystem II can be
      studied in vivo. 

PMID- 24311004
TI  - Light-emitting diodes as a light source for photosynthesis research.
AB  - Light-emitting diodes (LED) can provide large fluxes of red photons and so could
      be used to make lightweight, efficient lighting systems for photosynthetic
      research. We compared photosynthesis, stomatal conductance and isoprene emission
      (a sensitive indicator of ATP status) from leaves of kudzu (Pueraria lobata
      (Willd) Ohwi.) enclosed in a leaf chamber illuminated by LEDs versus by a xenon
      arc lamp. Stomatal conductance was measured to determine if red LED light could
      sufficiently open stomata. The LEDs produced an even field of red light (peak
      emission 656+/-5 nm) over the range of 0-1500 MUmol m(-2) s(-1). Under ambient
      CO2 the photosynthetic response to red light deviated slightly from the response
      measured in white light and stomatal conductance followed a similar pattern.
      Isoprene emission also increased with light similar to photosynthesis in white
      light and red light. The response of photosynthesis to CO2 was similar under the
      LED and xenon arc lamps at equal photosynthetic irradiance of 1000 MUmol m(-2) s(
      1). There was no statistical difference between the white light and red light
      measurements in high CO2. Some leaves exhibited feedback inhibition of
      photosynthesis which was equally evident under irradiation of either lamp type.
      Photosynthesis research including electron transport, carbon metabolism and trace
      gas emission studies should benefit greatly from the increased reliability,
      repeatability and portability of a photosynthesis lamp based on light-emitting
      diodes. 

PMID- 24311005
TI  - Serve as you go along.

PMID- 24311006
TI  - Sigmund freud by moonlight.
AB  - In this poetic essay the author seeks to isolate moments of lived experience that
      can provide an experiential grounding for understanding Freud's shift from his
      early naturalistic conceptual apparatus to the poetic metaphors ofAnanche,
      Thanatos, andEros. The author concludes that the latter conceptual apparatus is
      no longer narrowly clinical but rather existential, articulating a fundamental
      structure of being human. 

PMID- 24311007
TI  - Preventing mental illness through existential principles.
AB  - A case is made for the dysfunctional attributes of traditional marital
      relationships conceptually based upon the material principle of scarcity. The
      application of the existential principle of abundance is put forth for the
      purpose of developing genuine mutual support, personal awareness, and
      authenticity leading to the prevention of mental illness. 

PMID- 24311008
TI  - Religious youth cults: Alternative healing social networks.
AB  - The motivation of youth to join esoteric religious cults considered as
      psychopathology is a limited and reductionistic interpretation. Youthful devotees
      do demonstrate symptoms of psychic distress, which appear to be significantly
      ameliorated through participation in religious youth cults. Two major trends in
      social history reveal the sources of youth cults: loss of faith in the
      rationalistic Western cosmology and loss of the extended family system. The
      religious youth cult possesses many of the properties of the normal psychosocial
      system, which is a critical social structure for healthful coping in the world.
      As a normative social system, the religious youth cult is an alternative healing
      system for the existential crises of contemporary youth. 

PMID- 24311009
TI  - The recovery of feelings in a folktale.
AB  - The purpose of this essay is to explore the "symptom" of the denial of feelings
      and the subsequent recovery of feelings in relation to the task of uniting the
      human self. The spiritual, emotional, and physical implications of an exemplary
      narrative from the collection edited by Jacob and Wilhelm Grimm are discussed in
      relation to the "telescoping" of the emotion of fear, the sensation of
      shuddering, and the experience of anxiety about the integrity of the self. The
      reader is cautioned that the study of folktales enriches our telling of them and
      is itself justified by that telling. 

PMID- 24311010
TI  - The menstrual taboo in the Judeo-Christian tradition.
AB  - The menstrual taboo continues to be a primary reason why women in Judaism and
      Christianity are excluded from positions of authority. This is demonstrated by
      examining positions taken toward menstruation by religious leaders in past
      history and in the present day. Jesus and Gregory the Great are notable
      exceptions to the disdain expressed by male religionists toward menstruants. Only
      after the removal of this persistent taboo will religious bodies come to treat
      women as full participants. 

PMID- 24311011
TI  - The "WTL" model of cancer care.
AB  - Family conference and oncology tutoring programs have been attended by 1,000
      patients, family members, and support persons. Patients are taught to become
      active participants in their therapy, and families learn communication skills.
      Evaluation questionnaires reveal that ninety-four percent felt a significant
      improvement in family-patient communication. Ninety-three percent felt that
      personal needs related to the disease of cancer were accurately addressed. And
      ninety-seven percent indicated they would be referring others to the service. 

PMID- 24311012
TI  - Death and the "life review" in Halakhah.
AB  - Coping with old age involves resolving the task of "integrity versus despair,"
      which demands a nondefensive confrontation with the inevitability of death.
      Halakhah (Jewish ethics) also considered this task critical in later years of
      life, spoke of death's inevitability, and attempted to discourage denial of
      death. The Jewish approach seems compatible with Butler's concept of "life
      review" as a reconciliation with death and a reintegration of one's identity that
      occurs throughout later years. While the Eriksonian goal is confronting old age
      with a certain capacity for "wisdom," the rabbis maintained that such wisdom must
      culminate in the creative act of repentance. 

PMID- 24311013
TI  - Is the holocaust relevant to sociobiology?
AB  - Sociobiologists have emphasized that altruism and benevolent behavior are part of
      the genetic repertoire of most animals and certainly of man. They have
      constructed a theory of "ethics" as a biological phenomenon without reference to
      the concept of evil. It is concluded here however, that holocaust behavior is not
      equivalent to the "natural manifestation of an incompletely tamed animal flashing
      its teeth." Biologists have been too rigid in trying to equate "ethical behavior"
      with "social behavior." The added dimension of ethical behavior is a special kind
      of sensitivity to the needs of others, just as evil is the total lack of it. The
      evolution of this moral sense may itself have important selective value for the
      human species, whose survival depends on creating maximal diversity in its gene
      pool. 

PMID- 24311014
TI  - Value of diffusion-weighted and gadolinium-enhanced MRI for the diagnosis of
      pelvic recurrence from colorectal cancer.
AB  - PURPOSE: To prospectively assess the added value of gadolinium-enhanced and
      diffusion-weighted (DWI) MRI for the diagnosis of pelvic recurrence from
      colorectal cancer (CRC). MATERIALS AND METHODS: Fifty-two patients with suspected
      pelvic recurrence from CRC underwent pelvic MRI with T2-weighted ("T2"),
      gadolinium-enhanced fat-suppressed T1-weighted ("gadolinium") and DWI MR
      sequences. Three readers (senior radiologist: R1, two residents: R2, R3) scored
      the likelihood of recurrence on "T2," "T2 + DWI," and "T2 + Gadolinium." RESULTS:
      Twenty-seven patients had 42 sites of pelvic recurrence. On "T2," R1 achieved AUC
      of .95, sensitivity 88.4%, specificity 95.2%. For R2, these figures were .89,
      81.4%, 90.5%, for R3 .90, 83.7%, 76%. Both Gadolinium injection and DWI
      significantly improved AUCs for residents but not for the senior radiologist: up
      to .988 (R2, P = 0.006) and to .98 (R3, P = 0.01) with DWI and to .96 (R2, P =
      0.04), .98 (R3, P = 0.01) after gadolinium. All readers achieved slightly better
      AUCs with "T2 + DWI" than with "T2+Gadolinium" but not significantly (P = 0.68, P
      = 0.11, P = 0.3; respectively). CONCLUSION: For diagnosis of pelvic recurrence
      from CRC, both DWI and gadolinium-enhanced MRI significantly increase diagnostic
      performances compared with "T2" MRI for residents. DWI may be helpful in patients
      with contra-indications to intravenous administration of gadolinium.

PMID- 24311015
TI  - 25th anniversary article: Bulk heterojunction solar cells: understanding the
      mechanism of operation.
AB  - The status of understanding of the operation of bulk heterojunction (BHJ) solar
      cells is reviewed. Because the carrier photoexcitation recombination lengths are
      typically 10 nm in these disordered materials, the length scale for self-assembly
      must be of order 10-20 nm. Experiments have verified the existence of the BHJ
      nanostructure, but the morphology remains complex and a limiting factor. Three
      steps are required for generation of electrical power: i) absorption of photons
      from the sun; ii) photoinduced charge separation and the generation of mobile
      carriers; iii) collection of electrons and holes at opposite electrodes. The
      ultrafast charge transfer process arises from fundamental quantum uncertainty;
      mobile carriers are directly generated (electrons in the acceptor domains and
      holes in the donor domains) by the ultrafast charge transfer (~70%) with ~30%
      generated by exciton diffusion to a charge separating heterojunction. Sweep-out
      of the mobile carriers by the internal field prior to recombination is essential
      for high performance. Bimolecular recombination dominates in materials where the
      donor and acceptor phases are pure. Impurities degrade performance by introducing
      Shockly-Read-Hall decay. The review concludes with a summary of the problems to
      be solved to achieve the predicted power conversion efficiencies of >20% for a
      single cell. 

PMID- 24311016
TI  - Reassurance and distress behavior in preschool children undergoing dental
      preventive care procedures in a community setting: a multilevel observational
      study.
AB  - BACKGROUND: The effect of reassurance in managing distress among children who
      receive procedures of a less aversive nature has not been fully investigated.
      PURPOSE: This study aimed to investigate the relationship between reassurance by
      dental staff and distress behavior of preschool children receiving preventive
      procedures in a community setting. METHODS: Nurse-child interactions (n = 270)
      during fluoride varnish application were video recorded and coded. Multilevel
      logistic regression modeled the probability of the occurrence of child distress
      behavior as a function of reassurance provision, controlling for child-level and
      nurse-level variables. RESULTS: Child distress behavior was positively related to
      nurse verbal reassurance but negatively linked to the time that this reassurance
      occurred. Both child initial anxiety and nurse nonprocedural training increased
      the probability of observable distress behavior. CONCLUSIONS: The use of verbal
      reassurance to promote reception of mild invasive procedures was
      counterindicated, especially when offered early in the intervention (
      ClinicalTrials.gov number: NCT00881790).

PMID- 24311017
TI  - Perceived and objectively measured access to strength-training facilities and
      strength-training behavior.
AB  - BACKGROUND: The promotion of strength training is a public health priority.
      Employing both self-reported and objective assessment of environmental factors is
      helpful for a better understanding of the environmental influences on strength
      training behavior. PURPOSE: This study aims to investigate the associations of
      perceived and objectively measured access to strength-training facilities with
      strength-training behavior. METHODS: A cross-sectional questionnaire survey
      targeted 3,000 Japanese adults and 1,051 responded validly. Strength-training
      behavior, perceived access to facilities, and sociodemographic factors were
      assessed. Objective access to facilities was calculated using a geographic
      information system. Logistic regression analyses were conducted. RESULTS:
      Perceived good access to the facilities was significantly associated with
      strength-training behavior, whereas objective access to the facilities was not,
      even when adjusted for sociodemographic factors and other measures of access to
      strength-training facilities. CONCLUSIONS: Perceived access to the facilities may
      be a stronger predictor of strength-training behavior than objective access.

PMID- 24311018
TI  - Self-regulation of exercise behavior in the TIGER study.
AB  - OBJECTIVE: This study aimed to test experiential and behavioral processes of
      change as mediators of the prediction of exercise behavior by two self-regulation
      traits, self-efficacy and self-motivation, while controlling for exercise
      enjoyment. METHODS: Structural equation modeling was applied to questionnaire
      responses obtained from a diverse sample of participants. Objective measures
      defined adherence (928 of 1,279 participants attended 80 % or more of sessions)
      and compliance (867 of 1,145 participants exercised 30 min or more each session
      at their prescribed heart rate). RESULTS: Prediction of attendance by self
      efficacy (inversely) and self-motivation was direct and also indirect, mediated
      through positive relations with the typical use of behavioral change processes.
      Enjoyment and self-efficacy (inversely) predicted compliance with the exercise
      prescription. CONCLUSIONS: The results support the usefulness of self-regulatory
      behavioral processes of the transtheoretical model for predicting exercise
      adherence, but not compliance, extending the supportive evidence for self
      regulation beyond self-reports of physical activity used in prior observational
      studies.

PMID- 24311020
TI  - Bilateral abducens nerve palsy following ligamentous C1-C2 distraction.
AB  - PURPOSE: Posttraumatic abducens nerve palsy is well documented following head
      injury, but only few case reports exist on sixth nerve palsy after cervical spine
      trauma. Bilateral abducens palsy following vertical C1-C2 ligamentous distraction
      has not been described yet. METHODS: We report two patients who sustained motor
      vehicle accident-related C1-C2 distraction injury and were diagnosed with
      posttraumatic bilateral abducens nerve palsy. RESULTS: Patients underwent
      surgical stabilization of the upper cervical spine and demonstrated a remarkable
      recovery of the sixth nerve deficit up to 1 year after injury. CONCLUSION: We
      hypothesize that ligamentous C1-C2 distraction leads to caudal displacement of
      the brainstem in relation to the cranial base causing traction injury to the
      abducens nerve at its entry into Dorello's canal in the cavernous sinus.

PMID- 24311021
TI  - Elimination of endemic measles, rubella, and congenital rubella syndrome from the
      Western hemisphere: the US experience.
AB  - IMPORTANCE: To verify the elimination of endemic measles, rubella, and congenital
      rubella syndrome (CRS) from the Western hemisphere, the Pan American Health
      Organization requested each member country to compile a national elimination
      report. The United States documented the elimination of endemic measles in 2000
      and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease
      Control and Prevention convened an external expert panel to review the evidence
      and determine whether elimination of endemic measles, rubella, and CRS had been
      sustained. OBJECTIVE: To review the evidence for sustained elimination of endemic
      measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING,
      AND PARTICIPANTS: Review of data for measles from 2001 to 2011 and for rubella
      and CRS from 2004 to 2011 covering the US resident population and international
      visitors, including disease epidemiology, importation status of cases, molecular
      epidemiology, adequacy of surveillance, and population immunity as estimated by
      national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES:
      Annual numbers of measles, rubella, and CRS cases, by importation status,
      outbreak size, and distribution; proportions of US population seropositive for
      measles and rubella; and measles-mumps-rubella vaccination coverage levels.
      RESULTS: Since 2001, US reported measles incidence has remained below 1 case per
      1,000,000 population. Since 2004, rubella incidence has been below 1 case per
      10,000,000 population, and CRS incidence has been below 1 case per 5,000,000
      births. Eighty-eight percent of measles cases and 54% of rubella cases were
      internationally imported or epidemiologically or virologically linked to
      importation. The few cases not linked to importation were insufficient to
      represent endemic transmission. Molecular epidemiology indicated no endemic
      genotypes. The US surveillance system is adequate to detect endemic measles or
      rubella. Seroprevalence and vaccination coverage data indicate high levels of
      population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE: The
      external expert panel concluded that the elimination of endemic measles, rubella,
      and CRS from the United States was sustained through 2011. However, international
      importation continues, and health care providers should suspect measles or
      rubella in patients with febrile rash illness, especially when associated with
      international travel or international visitors, and should report suspected cases
      to the local health department.

PMID- 24311022
TI  - Validity and reliability of the Cold Discomfort Scale: a subjective judgement
      scale for the assessment of patient thermal state in a cold environment.
AB  - Complementary measures for the assessment of patient thermoregulatory state, such
      as subjective judgement scales, might be of considerable importance in field
      rescue scenarios where objective measures such as body core temperature, skin
      temperature, and oxygen consumption are difficult to obtain. The objective of
      this study was to evaluate, in healthy subjects, the reliability of the Cold
      Discomfort Scale (CDS), a subjective judgement scale for the assessment of
      patient thermal state in cold environments, defined as test-retest stability, and
      criterion validity, defined as the ability to detect a difference in cumulative
      cold stress over time. Twenty-two healthy subjects performed two consecutive
      trials (test-retest). Dressed in light clothing, the subjects remained in a
      climatic chamber set to -20  degrees C for 60 min. CDS ratings were obtained
      every 5 min. Reliability was analysed by test-retest stability using weighted
      kappa coefficient that was 0.84 including all the 5-min interval measurements.
      When analysed separately at each 5-min interval the weighted kappa coefficients
      were was 0.48-0.86. Criterion validity was analysed by comparing median CDS
      ratings of a moving time interval. The comparison revealed that CDS ratings were
      significantly increased for every interval of 10, 15, and 30 min (p < 0.001) but
      not for every interval of 5 min. In conclusion, in a prehospital scenario,
      subjective judgement scales might be a valuable measure for the assessment of
      patient thermal state. The results of this study indicated that, in concious
      patients, the CDS may be both reliable and valid for such purpose.

PMID- 24311023
TI  - Accurate and stable continuous monitoring module by mainstream capnography.
AB  - End-tidal partial pressure of [Formula: see text] is an important index in
      clinical monitoring. Medical mainstream capnography has become widely used, but
      there are still limitations in accuracy and stability. A type of mainstream
      capnometer based on the principle of non-dispersive infrared was designed. This
      capnometer inhibits signal drift by using electric modulation and thus ensures
      the accuracy of long-term CO2 monitoring. Statistical methods are used to find
      the best setting for sampling respiratory signals and improving precision.
      Several digital filtering techniques are used to process various interferences
      and improve capnogram quality. Clinical tests and targeted experiments show this
      mainstream capnometer can accurately monitor respiratory CO2 concentrations,
      especially at the end-tidal peak point. This capnometer also shows high accuracy
      and stability in long-term continuous monitoring. 

PMID- 24311025
TI  - Gomez-Lopez-hernandez syndrome versus rhombencephalosynapsis spectrum: a rare co
      occurrence with bipartite parietal bone.
AB  - Rhombencephalosynapsis (RES) is a rare hindbrain malformation that could occur in
      isolation or as a part of a syndrome for example, Gomez-Lopez-Hernandez syndrome
      (GLH) or VACTERL-H. We identified male patient with severe RES. Ventriculomegaly,
      agenesis of septum pellucidum, very thin corpus callosum with interhemispheric
      cyst were additional neuroimaging findings. He had brachyturricephaly, midface
      retrusion, low-set posteriorly rotated ears and bilateral parietal well
      circumscribed areas of alopecia. No corneal anesthesia was observed; thus,
      demonstrating many of the diagnostic criteria of GLH. Interestingly, he
      additionally had bilateral bipartite parietal bone (BPB) that is an extremely
      rare anomaly of the parietal sutures. This is the first co-occurrence of this
      rare anomaly with GLH. We believe the presence of this unique finding could
      represent an important clue for understanding the pathogenesis of this
      malformation.

PMID- 24311024
TI  - The aftermath of public housing relocations: relationships between changes in
      local socioeconomic conditions and depressive symptoms in a cohort of adult
      relocaters.
AB  - USA is experiencing a paradigm shift in public housing policy: while policies
      used to place people who qualified for housing assistance into spatially
      concentrated housing complexes, they now seek to geographically disperse them,
      often to voucher-subsidized rental units in the private market. Programs that
      relocate residents from public housing complexes tend to move them to
      neighborhoods that are less impoverished and less violent. To date, studies have
      reached conflicting findings about the relationship between public housing
      relocations and depression among adult relocaters. The present longitudinal
      multilevel analysis tests the hypothesis that pre-/postrelocation improvements in
      local economic conditions, social disorder, and perceived community violence are
      associated with declines in depressive symptoms in a cohort of African-American
      adults; active substance misusers were oversampled. We tested this hypothesis in
      a cohort of 172 adults who were living in one of seven public housing complexes
      scheduled for relocation and demolition in Atlanta, GA; by design, 20% were
      dependent on substances and 50% misused substances but were not dependent.
      Baseline data captured prerelocation characteristics of participants; of the
      seven census tracts where they lived, three waves of postrelocation data were
      gathered approximately every 9 months thereafter. Surveys were administered at
      each wave to assess depressive symptoms measured using the Center for
      Epidemiologic Studies Depression Scale (CES-D), perceived community violence, and
      other individual-level covariates. Participants' home addresses were geocoded to
      census tracts at each wave, and administrative data sources were used to
      characterize tract-level economic disadvantage and social disorder. Hypotheses
      were tested using multilevel models. Between waves 1 and 2, participants
      experienced significant improvements in reported depressive symptoms and
      perceived community violence and in tract-level economic disadvantage and social
      disorder; these reductions were sustained across waves 2-4. A 1 standard
      deviation improvement in economic conditions was associated with a 1-unit
      reduction in CES-D scores; the magnitude of this relationship did not vary by
      baseline substance misuse or gender. Reduced perceived community violence also
      predicted lower CES-D scores. Our objective measure of social disorder was
      unrelated to depressive symptoms. We found that relocaters who experienced
      greater pre-/postrelocation improvements in economic conditions or in perceived
      community violence experienced fewer depressive symptoms. Combined with past
      research, these findings suggest that relocation initiatives should focus on the
      quality of the places to which relocaters move; future research should also
      identify pathways linking pre-/postrelocation changes in place characteristics to
      changes in mental health.

PMID- 24311026
TI  - Chiral Cp-rhodium(III)-catalyzed asymmetric hydroarylations of 1,1-disubstituted
      alkenes.
AB  - Metal-catalyzed functionalizations at the ortho position of a directing group
      have become an efficient bond-forming strategy. A wide range of transformations
      that employ Cp*Rh(III) catalysts have been described, but despite their synthetic
      potential, enantioselective variants that use chiral versions of the Cp* ligand
      remain scarce (Cp*=pentamethyl cyclopentadienyl). Cyclopentadienyl compounds with
      an atropchiral biaryl backbone are shown to be suitable ligands for the efficient
      intramolecular enantioselective hydroarylation of aryl hydroxamates.
      Dihydrofurans that bear methyl-substituted quaternary stereocenters are thus
      obtained by C?H functionalization under mild conditions. 

PMID- 24311027
TI  - Bulimia nervosa patient diagnosed with previously unsuspected ADHD in adulthood:
      clinical case report, literature review, and diagnostic challenges.
AB  - There is increasing literature suggesting a link between attention-deficit
      hyperactivity disorder (ADHD) and eating disorders (EDs), especially bulimia
      nervosa. ADHD is under-diagnosed in girls and children of high intelligence are
      typically missed. We identified a case of a 23-year-old woman suffering from
      severe bulimia nervosa and previously unsuspected ADHD in adulthood; we diagnosed
      and treated her with extended-release methylphenidate. We performed a literature
      review on the ADHD and bulimia nervosa comorbidity. We discuss the reasons why
      her ADHD remained undiagnosed and the difficulties in diagnosing ADHD in patients
      with EDs. We suggest that identifying comorbid ADHD is crucial for these patients
      and argue for the use of a structured interview, collateral history and
      investigation of onset of symptoms to establish a diagnosis of ADHD in adults
      with bulimia nervosa. Comorbidities and overlap of symptomatology need to be
      taken into account.

PMID- 24311029
TI  - Time course of hormonal control of the first mitosis in tobacco mesophyll
      protoplasts cultivated in vitro.
AB  - The presence of auxin and cytokinin is necessary for the induction of mitosis in
      tobacco mesophyll protoplasts cultivated in vitro. In their absence, protoplasts
      firstly accumulate inhibitors of mitosis in the culture medium, possibly because
      of non-coordinated cell-wall synthesis, and secondly evolve a nonmitotic and
      degenerative metabolism. By changing the intoxified medium, it is possible to
      show that auxin is necessary from the beginning of culture, while cytokinin is
      only required later to allow a step in the development of the mitotic apparatus. 

PMID- 24311028
TI  - Persistence in fluctuating environments for interacting structured populations.
AB  - Individuals within any species exhibit differences in size, developmental state,
      or spatial location. These differences coupled with environmental fluctuations in
      demographic rates can have subtle effects on population persistence and species
      coexistence. To understand these effects, we provide a general theory for
      coexistence of structured, interacting species living in a stochastic
      environment. The theory is applicable to nonlinear, multi species matrix models
      with stochastically varying parameters. The theory relies on long-term growth
      rates of species corresponding to the dominant Lyapunov exponents of random
      matrix products. Our coexistence criterion requires that a convex combination of
      these long-term growth rates is positive with probability one whenever one or
      more species are at low density. When this condition holds, the community is
      stochastically persistent: the fraction of time that a species density goes below
      delta approaches zero as delta approaches zero. Applications to predator-prey
      interactions in an autocorrelated environment, a stochastic LPA model, and
      spatial lottery models are provided. These applications demonstrate that positive
      autocorrelations in temporal fluctuations can disrupt predator-prey coexistence,
      fluctuations in log-fecundity can facilitate persistence in structured
      populations, and long-lived, relatively sedentary competing populations are
      likely to coexist in spatially and temporally heterogeneous environments.

PMID- 24311030
TI  - Penetration of chemicals into the Malus leaf cuticle : An ultrastructural
      analysis.
AB  - The adaxial leaf cuticle of Malus pumila was examined by electron microscopy to
      determine possible avenues for transcuticular movement of foliarly applied
      chemicals. Cutin-embedded polysaccharide microfibrils originated at the outer
      epidermal cell wall and occasionally extended to the cuticle surface. Lamellae,
      ca. 4 nm wide, usually were oriented parallel to the cuticle surface. When
      oriented perpendicular to the surface, they extended nearly to the subjacent wall
      layer from the surface. Aqueous solutions of uranyl acetate, silver nitrate and
      phenyl mercuric acetate applied to the cuticle surface of leaf segments floated
      on solutions of phosphate salts or thiocarbohydrazide (TCH) reacted within the
      cuticle to form insoluble electron-opaque deposits indicative of their avenues of
      transcuticular movement. Uranyl phosphate deposits were observed only in the
      polysaccharide microfibrils of chloroform: methanolextracted leaves. Silver-TCH
      deposits were observed in the microfibrils of both extracted and nonextracted
      leaf cuticles. Phenyl mercuric acetate-TCH deposits were randomly dispersed
      throughout the extracted cuticle and not associated with the polysaccharide
      microfibrils. 

PMID- 24311031
TI  - Measurement of nitrite reductase in leaf tissue of Vigna mungo : A new method.
AB  - The enzyme nitrite reductase (EC 1.6.6.4) is generally assayed in terms of
      disappearance of nitrite from the assay medium. We describe a technique which
      allowed estimation of the enzyme level in leaf tissues of Vigna mungo (L). Hepper
      in terms of the release of the product (NH3) of the enzyme reaction. The
      technique is offered as an alternative, possibly more convenient method for assay
      of nitrite reductase in plant tissue in vivo. 

PMID- 24311032
TI  - Rhythmic changes in transcriptional activity during the development of potato
      tubers.
AB  - Chromatin-bound, DNA-dependent RNA polymerase (EC 2.7.7.6) activity and chromatin
      template availability, as measured with saturating amounts of E. coli RNA
      polymerase, changes rhythmically during the formation, dormancy, and sprouting of
      potato tubers. Active growth processes coincide with the highest RNA polymerase
      activity as well as the greatest template accessibility, during tuberization and
      sprouting. Consequently, chromatin-associated RNA and protein content is highest
      in young developing tubers and in old tubers at the onset of sprouting. Ribosomal
      RNA content, in turn, is maximal in small tubers, remains constant during
      dormancy, and decreases when sprouting begins, probably due to the translocation
      of rRNA into the sprouts. The nucleolus changes its shape and size concomitantly
      with the process of tuberization. 

PMID- 24311033
TI  - Age-dependent variations in transcriptional response to wounding and gibberellic
      acid in a higher plant.
AB  - The reaction of potato tuber tissue upon wounding and gibberellic acid (GA3)
      treatment is strictly dependent on the tuber age. Young, rapidly growing tubers
      decline both chromatin-bound, DNA-dependent RNA polymerase (EC 2.7.7.6) activity
      and template availability as a consequence of wounding and are not responsive
      toward GA3. At the onset of dormancy, ripened tubers do not at all respond to
      wounding or hormones, but later on develop the ability to increase their
      transcriptional rate and template accessibility, both after injury and treatment
      with 10(-7) mol l(-1) GA3. The size of the nucleolus and the rRNA content of the
      ribosomal population follows the same pattern. 

PMID- 24311034
TI  - Interaction of hydrolytic and phosphorolytic enzymes of starch metabolism in
      Kalanchoe daigremontiana.
AB  - The degradation of starch by a protein fraction of Kalanchoe daigremontiana Hamet
      et Perrier, obtained by ammoniumsulfate precipitation (30-70%), was found to be
      catalyzed by alpha-and beta-amylase (EC 3.2.1.1 and EC 3.2.1.2, respectively) and
      by starch phosphorylase (EC 2.4.1.1). The activity of these enzymes was
      determined by chromatographic analysis of the reaction products; separation and
      identification of alpha-amylase was accomplished by heat-inactivation of beta
      amylase and alpha-glucosidase. When the interaction of amylolytic and
      phosphorolytic enzymes was comparatively studied, it was found that without
      inorganic phosphorus in the reaction mixture, (14)C-starch was converted
      predominantly to maltose and glucose; supplementation with 1-10 mM orthophosphate
      (Pi) resulted in an increase in glucose-1-phosphate formation and a concomitant
      reduction of maltose production. Since the total volume of starch degradation
      remained approximately constant, Pi apparently inhibits beta-amylase (Ki about 3
      mM Pi). Thus, free Pi in the cell participates in the regulation of starch
      catabolism, serving as a substrate for starch phosphorylase while simultaneously
      reducing the production of maltose. With respect to glucan synthesis,
      adenosinediphosphoglucose-alpha-1,4-glucosyltransferase (EC 2.4.1.22), maltose
      phosphorylase and maltoseglucosyltransferase were also found to be active. The
      last-named enzyme catalyzes an exchange between dextrins and is considered to
      provide primer carbohydrates for the synthesis of polyglucans. 

PMID- 24311035
TI  - Effects of temperature and sink activity on the transport of (14)C-labelled indol
      3yl-acetic acid in the intact pea plant (Pisum sativum L.).
AB  - The velocity and intensity of basipetal transport of (14)C-labelled indol-3yl
      acetic acid (IAA) applied to the apical bud of the intact pea plant were
      influenced by the temperature to which the stem was exposed and were not
      influenced by changes in the temperature of the root system when this was
      controlled independently between 5 degrees C and 35 degrees C. The velocity of
      transport increased steadily with temperature to a maximum in excess of 35
      degrees C and then fell sharply with further increase in temperature. The Q10 for
      velocity, determined from Arrhenius plots, was low (ca. 1.3). Transport intensity
      increased to a maximum at about 25 degrees C (Q10=2.2) and then declined
      gradually with further increase in temperature. It is suggested that transport
      velocity and transport intensity are controlled independently.The characteristics
      of auxin transport through the stem were not affected by removal of the root
      system, or by the withdrawl of root aeration. Labelled IAA did not pass a region
      of the stem cooled to about 1.0 degrees C, or through a narrow zone of stem
      tissue killed by heat treatment. In the latter case the heat treatment was shown
      not to interfere with the upward transport of water in the xylem. Labelled IAA
      continued to move into, and to accumulate in, the tissues immediately above a
      cooled or heat-killed region of the stem. It was concluded that the long-distance
      basipetal transport of auxin through the stem of the intact plant is driven by
      the transporting cells themselves and is independent of the activity of sinks for
      the transported auxin.The fronts of the observed tracer profiles in the stem were
      closely fitted by error function diffusion analogue curves. However, diffusion of
      IAA alone could not account for the observed characteristics of the transport and
      it is suggested that the curvilinear fronts of the profiles resulted from a
      diffusive mixing of exogenous IAA (or IAA-carrier complexes) with endogenous IAA
      already in the transport pathway. 

PMID- 24311036
TI  - Identification of gibberellin A1 in the embryo suspensor of Phaseolus coccineus.
AB  - By combined gas chromatography-mass spectrometry the gibberellin present in
      suspensors of heart-shaped embryos of Phaseolus coccineus has been identified as
      Gibberellin A1 (GA1). The amount of GA1 in 2000 suspensors (452 mg), as estimated
      by gas chromatography. was 4MUg. The presence of GA1 in suspensors of P.
      coccineus is discussed in relation to our present knowledge of the occurrence of
      many gibberellins in developing seeds and immature fruits of the same species. 

PMID- 24311037
TI  - Control of mitochondrial activities by phytochrome during greening.
AB  - Mitochondria isolated from 7-day old darkgrown Avena sativa L. (var. Arnold)
      laminae given 5 min illumination of red light, followed by varying lengths of
      darkness up to 3 h, showed at least a twofold increase in the rates of both NADH
      dependent oxygen consumption and respiratory chain phosphorylation over those of
      mitochondria isolated from unilluminated tissue. Similar organelles, isolated
      from tissue given either far-red or red followed by far-red pretreatment,
      exhibited rates of both functions of between 25% and 75% below those of the
      mitochondria from unilluminated tissue. The induction-reversion criteria for
      phytochrome control of respiration and oxidative phosphorylation were satisfied
      under all experimental conditions during the greening process.Treatment with
      continuous far-red light, acting presumably through the 'high irradiance'
      reaction of phytochrome, served to disengage phytochrome activity from
      photosynthesis. The stimulation of oxidative phosphorylation still occurred under
      these conditions, slightly slower but much more prolonged in the absence of ATP
      from photophosphorylation. 

PMID- 24311038
TI  - Quantitative studies of embryogenesis in normal and 5-methyltryptophan-resistant
      cell lines of wild carrot : The effects of growth regulators.
AB  - The frequency of embryo formation was determined in normal and 5-methyltryptophan
      resistant (5-MT(r)) cell lines of wild carrot (Daucus carota L.) grown in the
      presence or absence of 2-isopentenyladenine (2-ip) and 2,4-dichlorophenoxyacetic
      acid (2,4-D). 2-ip stimulated the intitation of embryo formation and also
      accelerated embryo development. 2.4-D inhibited embryo differentiation at several
      stages: at 0.1 mg/l, it stopped regeneration at the earliest stage, resulting in
      callus growth instead of embryo formation; at 0.04 mg/l 2,4-D, some globular
      embryos were produced, but they did not develop into more advanced embryos.
      Variant cell lines with higher levels of auxin (indole-3-acetic acid, IAA) were
      used to study the effect of an elevated endogenous concentration of auxin on
      embryogenesis. IAA at these concentrations suppressed regeneration in the same
      manner as the exogenous auxin, 2,4-D, did. This result confirms the hypothesis
      that high levels of IAA are responsible for the suppression of regeneration in
      the 5-MT(r) cell lines. 

PMID- 24311039
TI  - Kinetic characteristics of photoassimilate translocation in Alaria esculenta
      (Laminariales, Phaeophyceae).
AB  - The kinetics of translocation of (14)C-labeled photoassimilate were studied in
      the kelp, Alaria esculenta (L.) Grev., using a Geiger-Muller detector-probe to
      measure radioactivity in the source and sink regions of dumbbell-shaped explants
      cut from blades. Rapid tracer efflux from the source occurred for 4 days
      following a pulse of [(14)C]bicarbonate, with 40-60% of the initial activity
      remaining in the source after 10-14 days. Portions of source and sink tissue were
      analysed for distribution of radioactivity in mannitol, amino-acid, organic-acid
      and insoluble fractions. About 75% of the radioactivity in both source and sink
      at the end of the experiments was in soluble organic matter. The translocation
      velocity of the moving solute front (1.0-1.6 cm.h(-1)) was derived from time
      course profiles of tracer arriving in Alaria sinks. Relative rates of
      translocation, calculated from these profiles, yielded skewed curves, with
      maximum rates of import by the sink occurring 72-96 h after the source was
      pulsed. 

PMID- 24311040
TI  - Fatty-acid metabolism in senescing and regreening soybean cotyledons.
AB  - Changes in fatty-acid metabolism were studied in soybean (Glycine max Merr.)
      cotyledons during senescence as well as in cotyledons which had been caused to
      regreen by removal of the epicotyl from the seedling. The activities of the
      enzymes acetyl-CoA synthetase (EC 6.2.1.1) and fatty-acid synthetase in plastids
      isolated from the cotyledons decreased during senescence but increased in
      response to regreening. These changes in enzyme activities followed the same
      pattern as changes in the quantities of chlorophyll and polyunsaturated fatty
      acids in this tissue. The in-vivo incorporation of [(14)C]acetate into total
      fatty acids in the senescing and regreening cotyledons did not vary markedly with
      age. In addition, the quantity of label in fatty acids did not decrease for as
      much as 60 h after the removal of the substrate. During this 60-h period however,
      there was substantial redistribution of the label among the individual fatty
      acids. While the labelling pattern of the individual fatty acids did not vary
      significantly with respect to age in the senescing cotyledons, there was a
      substantial increase in the synthesis of labelled polyunsaturated fatty acids in
      the regreening tissue. Thus, the incorporation of [(14)C]acetate into fatty acids
      did not reflect the changes in the quantities of the individual fatty acids in
      senescing tissue as well as they did in regreening tissue. 

PMID- 24311041
TI  - Identification of gibberellin A9 methyl ester as a natural substance regulating
      formation of reproductive organs in Lygodium japonicum.
AB  - Prothallia of Lygodium japonicum (Thunb.) Sw. were aseptically cultured under
      white light in a mineral solution. Solvent fractionation of the resultant culture
      medium and subsequent preparative thinlayer chromatography yielded a fraction
      that induced antheridium formation and inhibited archegonium formation. Combined
      gas chromatography-selected ion monitoring analysis of this fraction confirmed
      the presence of gibberellin A9 methyl ester (GA9-me) as an antheridiogen and an
      inhibitor of archegonium formation. Exogenously applied [(3)H]GA9 was rapidly
      converted to [(3)H]GA9-me in the prothallial tissue. Authentic GA9-me was active
      to 10(-10)M in antheridium formation and to 10(-9)M in the inhibition of
      archegonium formation. 

PMID- 24311042
TI  - The occurrence of both C3 and C 4 photosynthetic characteristics in a single Zea
      mays plant.
AB  - The activities of the carboxylating enzymes ribulose-1,5-biphosphate (RuBP)
      carboxylase and phosphoenolpyruvate (PEP) carboxylase in leaves of three-week old
      Zea mays plants grown under phytotron conditions were found to vary according to
      leaf position. In the lower leaves the activity of PEP carboxylase was lower than
      that of RuBP carboxylase, while the upper leaves exhibited high levels of PEP
      carboxylase. Carbon dioxide compensation points and net photosynthetic rates also
      differed in the lower and upper leaves. Differences in the fine structure of the
      lowermost and uppermost leaves are shown. The existence of both the C3 and C4
      photosynthetic pathways in the same plant, in this and other species, is
      discussed. 

PMID- 24311043
TI  - Interaction of [(3)H]gibberellin A 1 with a sub-cellular fraction from lettuce
      (Lactuca sativa L.) hypocotyls : Requirement for protein synthesis.
AB  - The relationship between protein synthesis and the incorporation of
      [(3)H]gibberellin A1 ([(3)H]GA1) into a 2,000xg pelletable (2KP) fraction from
      lettuce (Lactuca sativa L.) hypocotyl sections has been investigated.
      Concentrations of D-2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamide (MDMP)
      between 10(-7) M and 10(-4) M caused increasing inhibition of growth, 2KP
      labelling and incorporation of [(14)C]leucine into soluble protein. Growth and
      2KP radioactivity were highly correlated (r=0.996). Transfer to MDMP early or
      late in the course of GA response caused reductions in both growth and
      incorporation into the 2KP fraction. Exposure to the inhibitor had more effect at
      4 h than at 20 h. The proportions of alkali-soluble and insoluble radioactivity
      in the 2KP fraction were also altered by this treatment. The implications of
      these findings are discussed. 

PMID- 24311044
TI  - Relevance of deep-subsurface microbiology for underground gas storage and
      geothermal energy production.
AB  - This chapter gives the reader an introduction into the microbiology of deep
      geological systems with a special focus on potential geobiotechnological
      applications and respective risk assessments. It has been known for decades that
      microbial activity is responsible for the degradation or conversion of
      hydrocarbons in oil, gas, and coal reservoirs. These processes occur in the
      absence of oxygen, a typical characteristic of such deep ecosystems. The
      understanding of the responsible microbial processes and their environmental
      regulation is not only of great scientific interest. It also has substantial
      economic and social relevance, inasmuch as these processes directly or indirectly
      affect the quantity and quality of the stored oil or gas. As outlined in the
      following chapter, in addition to the conventional hydrocarbons, new interest in
      such deep subsurface systems is rising for different technological developments.
      These are introduced together with related geomicrobiological topics. The capture
      and long-termed storage of large amounts of carbon dioxide, carbon capture and
      storage (CCS), for example, in depleted oil and gas reservoirs, is considered to
      be an important options to mitigate greenhouse gas emissions and global warming.
      On the other hand, the increasing contribution of energy from natural and
      renewable sources, such as wind, solar, geothermal energy, or biogas production
      leads to an increasing interest in underground storage of renewable energies.
      Energy carriers, that is, biogas, methane, or hydrogen, are often produced in a
      nonconstant manner and renewable energy may be produced at some distance from the
      place where it is needed. Therefore, storing the energy after its conversion to
      methane or hydrogen in porous reservoirs or salt caverns is extensively
      discussed. All these developments create new research fields and challenges for
      microbiologists and geobiotechnologists. As a basis for respective future work,
      we introduce the three major topics, that is, CCS, underground storage of gases
      from renewable energy production, and the production of geothermal energy, and
      summarize the current stat of knowledge about related geomicrobiological and
      geobiotechnological aspects in this chapter. Finally, recommendations are made
      for future research.

PMID- 24311045
TI  - Understanding understanding.

PMID- 24311046
TI  - A developmental perspective on religious orientation dimensions.
AB  - L.B. Brown's model of religious faith posits two bipolar religious orientations
      (intrinsic-extrinsic and autonomy-observance) that represent a two-dimensional
      space in which a religious believer can be located. This paper proposes a
      developmental sequence within Brown's model. The psychometric tradition of
      religious orientations is combined with a developmental tradition. The
      developmental process is consistent with models by A. Maslow, L. Kohlberg, J.
      Fowler, and J. Loevinger. Religious faith typically springs from extrinsic
      motivations. Most religious adherents achieve the next level, "observance," or
      identification with a religious community and its creeds. Some progress to
      intrinsic religiousness, and fewer attain religious autonomy. 

PMID- 24311047
TI  - Clergy involvement in occupational safety and health.
AB  - The toll exacted by occupational injuries and illnesses on employed people
      involves a degree of personal and family suffering of such magnitude that clergy
      can legitimately consider it a part of their pastoral responsibilities to address
      the problem. Several cogent reasons for clergy involvement in occupational safety
      and health are provided, along with approaches clergy can implement to help
      parishioners reduce their workplace risks. Resources for assistance in engaging
      in these activities are suggested. 

PMID- 24311048
TI  - Moon over academe.
AB  - The authors consider critically the Annual International Conference of the Unity
      of the Sciences (ICUS) sponsored by S.M. Moon. Thirty eminent scientists who had
      endorsed ICUS responded to a personal letter. By analyzing their replies
      systematically, we identified their rationales in the face of anti-cult
      publicity. Our experiences represent a case history in the calculated
      misapplication of the principles of open expression, religious freedom, and the
      search for values. 

PMID- 24311049
TI  - Reminiscence as the cure of souls in early old age.
AB  - Reminiscing is an important step in the direction of spiritual maturity and
      wholeness for the person in early old age. Reminiscence that is shared between
      persons easily fits into the early Christian concept of cure. It is an act of
      loving care that heals and helps shape the totality of existence. Therapeutic
      reminiscence not only enhances the cure of souls in early old age; it also helps
      to close the gap between the depressing expectations of younger generations and
      the reality of continued growth in the last half of life. A bibliography is
      appended. 

PMID- 24311050
TI  - Filipino psychic surgery: Myth, magic, or miracle.
AB  - This essay considers the current impact and evaluation of Far Eastern psychic
      healing typified by the psychic surgery of the Philippine Islands. On the basis
      of a literature survey as well as interviews with persons who had visited the
      healers and received psychic surgery, an analysis of the spiritual dynamics and
      physical effects is reported. An attempt is made to balance the positive reports
      of those who were healed with the more objective and/or skeptical reports of
      religious and scientific leaders. Cultural, psychological, medical, and magical
      aspects are considered. An expansion of philosophic outlook coupled with a search
      for new tools of investigation is suggested. 

PMID- 24311051
TI  - Saint Paul's approach to grief: Clarifying the ambiguity.
AB  - There is a certain ambiguity in the Christian approach to grief that dates back
      to St. Paul. Paul stood at the crossroads of two traditional approaches to grief:
      the lamentation stradition, encouraging the full, free expression of grief
      emotions, and the consolation tradition, which encouraged restraint, moderation,
      and patience. Paul's pastoral approach to grief reflects elements of both
      traditions, synthesized to fit his own unique theological context. The modern
      pastor, informed by current thinking in psychology, faces a similar challenge. To
      facilitate one's own synthesis, the pastor must begin by clarifying his/her
      psychological assumptions about the nature of health and his/her theological
      assumptions about the nature of loss. 

PMID- 24311052
TI  - A palladium label to monitor nanoparticle-assisted drug delivery of a
      photosensitizer into tumor spheroids by elemental bioimaging.
AB  - In this study, the cellular uptake of the second generation photosensitizer
      5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) was investigated using
      laser ablation coupled to inductively coupled plasma mass spectrometry (LA-ICP
      MS) at a spatial resolution of 10 MUm. To achieve high sensitivity, the
      photosensitizer was tagged with palladium. As a tumor model system, a 3D cell
      culture of the TKF-1 cell line was used. These tumor spheroids were incubated
      with the Pd-tagged photosensitizer embedded in poly(lactic-co-glycolic acid)
      (PLGA) nanoparticles to investigate the efficiency of nanoparticle based drug
      delivery. An accumulation of the drug in the first cell layers of the tumor
      spheroid was observed. In the case of nanoparticle based drug delivery, a
      significantly more homogeneous distribution of the photosensitizer was achieved,
      compared to tumor spheroids incubated with the dissolved photosensitizer without
      the nanoparticular drug delivery system. The infiltration depth of the Pd-tagged
      photosensitizer could not be increased with rising incubation time, which can be
      attributed to the adsorption of the photosensitizer onto cellular components. 

PMID- 24311053
TI  - Reporting of a randomized controlled trial of Tibetan sound meditation and
      cognitive functioning among breast cancer patients.

PMID- 24311056
TI  - Reversible and irreversible chemisorption in nonporous-crystalline hybrids.
AB  - The tools of synthetic chemistry allow us to fine-tune the reactivity of
      molecules at a level of precision not yet accessible with inorganic solids. We
      have investigated hybrids that couple molecules to the superior thermal and
      mechanical properties of solids. Herein we present, to the best of our knowledge,
      the first demonstration of reactivity between hybrid perovskites and substrates.
      Reaction with iodine vapor results in a remarkable expansion of these materials
      (up to 36 % in volume) where new covalent C?I bonds are formed with retention of
      crystallinity. These hybrids also show unusual examples of reversible
      chemisorption. Here, solid-state interactions extend the lifetime of molecules
      that cannot be isolated in solution. We have tuned the half-lives of the
      iodinated structures from 3 h to 3 days. These nonporous hybrids drive substrate
      capture and controlled release through chemical reactivity. We illustrate the
      strengths of the hybrid by considering radioactive iodine capture. 

PMID- 24311057
TI  - Dynamic topographical pattern classification of multichannel prefrontal NIRS
      signals: II. Online differentiation of mental arithmetic and rest.
AB  - OBJECTIVE: Near-infrared spectroscopy (NIRS) has recently gained attention as a
      modality for brain-computer interfaces (BCIs), which may serve as an alternative
      access pathway for individuals with severe motor impairments. For NIRS-BCIs to be
      used as a real communication pathway, reliable online operation must be achieved.
      Yet, only a limited number of studies have been conducted online to date. These
      few studies were carried out under a synchronous paradigm and did not accommodate
      an unconstrained resting state, precluding their practical clinical implication.
      Furthermore, the potentially discriminative power of spatiotemporal
      characteristics of activation has yet to be considered in an online NIRS system.
      APPROACH: In this study, we developed and evaluated an online system-paced NIRS
      BCI which was driven by a mental arithmetic activation task and accommodated an
      unconstrained rest state. With a dual-wavelength, frequency domain near-infrared
      spectrometer, measurements were acquired over nine sites of the prefrontal
      cortex, while ten able-bodied participants selected letters from an on-screen
      scanning keyboard via intentionally controlled brain activity (using mental
      arithmetic). Participants were provided dynamic NIR topograms as continuous
      visual feedback of their brain activity as well as binary feedback of the BCI's
      decision (i.e. if the letter was selected or not). To classify the hemodynamic
      activity, temporal features extracted from the NIRS signals and spatiotemporal
      features extracted from the dynamic NIR topograms were used in a majority vote
      combination of multiple linear classifiers. MAIN RESULTS: An overall online
      classification accuracy of 77.4 +/- 10.5% was achieved across all participants.
      The binary feedback was found to be very useful during BCI use, while not all
      participants found value in the continuous feedback provided. SIGNIFICANCE: These
      results demonstrate that mental arithmetic is a potent mental task for driving an
      online system-paced NIRS-BCI. BCI feedback that reflects the classifier's
      decision has the potential to improve user performance. The proposed system can
      provide a framework for future online NIRS-BCI development and testing.

PMID- 24311058
TI  - The scene and the unseen: manipulating photographs for experiments on change
      blindness and scene memory: image manipulation for change blindness.
AB  - The change blindness paradigm, in which participants often fail to notice
      substantial changes in a scene, is a popular tool for studying scene perception,
      visual memory, and the link between awareness and attention. Some of the most
      striking and popular examples of change blindness have been demonstrated with
      digital photographs of natural scenes; in most studies, however, much simpler
      displays, such as abstract stimuli or "free-floating" objects, are typically
      used. Although simple displays have undeniable advantages, natural scenes remain
      a very useful and attractive stimulus for change blindness research. To assist
      researchers interested in using natural-scene stimuli in change blindness
      experiments, we provide here a step-by-step tutorial on how to produce changes in
      natural-scene images with a freely available image-processing tool (GIMP). We
      explain how changes in a scene can be made by deleting objects or relocating them
      within the scene or by changing the color of an object, in just a few simple
      steps. We also explain how the physical properties of such changes can be
      analyzed using GIMP and MATLAB (a high-level scientific programming tool).
      Finally, we present an experiment confirming that scenes manipulated according to
      our guidelines are effective in inducing change blindness and demonstrating the
      relationship between change blindness and the physical properties of the change
      and inter-individual differences in performance measures. We expect that this
      tutorial will be useful for researchers interested in studying the mechanisms of
      change blindness, attention, or visual memory using natural scenes.

PMID- 24311059
TI  - Algorithmic complexity for short binary strings applied to psychology: a primer.
AB  - As human randomness production has come to be more closely studied and used to
      assess executive functions (especially inhibition), many normative measures for
      assessing the degree to which a sequence is randomlike have been suggested.
      However, each of these measures focuses on one feature of randomness, leading
      researchers to have to use multiple measures. Although algorithmic complexity has
      been suggested as a means for overcoming this inconvenience, it has never been
      used, because standard Kolmogorov complexity is inapplicable to short strings
      (e.g., of length l <= 50), due to both computational and theoretical limitations.
      Here, we describe a novel technique (the coding theorem method) based on the
      calculation of a universal distribution, which yields an objective and universal
      measure of algorithmic complexity for short strings that approximates Kolmogorov
      Chaitin complexity.

PMID- 24311060
TI  - The Arena System: a novel shared touch-panel apparatus for the study of
      chimpanzee social interaction and cognition.
AB  - We report on the development of a novel shared touch-panel apparatus for
      examining a diverse range of topics in great ape social cognition and
      interaction. Our apparatus-named the Arena System-is composed of a single
      multitouch monitor that spans across two separate testing booths, so that
      individuals situated in each booth have tactile access to half of the monitor and
      visual access to the whole monitor. Additional components of the system include a
      smart-film barrier able to restrict visual access between the booths, as well as
      two automated feeding devices that dispense food rewards to the subjects. The
      touch-panel, smart-film, and feeders are controlled by a PC that is also
      responsible for running the experimental tasks. We present data from a pilot
      behavioral game theory study with two chimpanzees in order to illustrate the
      efficacy of our method, and we suggest applications for a range of topics
      including animal social learning, coordination, and behavioral economics. The
      system enables fully automated experimental procedures, which means that no human
      participation is needed to run the tasks. The novel use of a touch-panel in a
      social setting allows for a finer degree of data resolution than do the
      traditional experimental apparatuses used in prior studies on great ape social
      interaction. 

PMID- 24311061
TI  - Psychometric challenges and proposed solutions when scoring facial emotion
      expression codes.
AB  - Coding of facial emotion expressions is increasingly performed by automated
      emotion expression scoring software; however, there is limited discussion on how
      best to score the resulting codes. We present a discussion of facial emotion
      expression theories and a review of contemporary emotion expression coding
      methodology. We highlight methodological challenges pertinent to scoring software
      coded facial emotion expression codes and present important psychometric research
      questions centered on comparing competing scoring procedures of these codes.
      Then, on the basis of a time series data set collected to assess individual
      differences in facial emotion expression ability, we derive, apply, and evaluate
      several statistical procedures, including four scoring methods and four data
      treatments, to score software-coded emotion expression data. These scoring
      procedures are illustrated to inform analysis decisions pertaining to the scoring
      and data treatment of other emotion expression questions and under different
      experimental circumstances. Overall, we found applying loess smoothing and
      controlling for baseline facial emotion expression and facial plasticity are
      recommended methods of data treatment. When scoring facial emotion expression
      ability, maximum score is preferred. Finally, we discuss the scoring methods and
      data treatments in the larger context of emotion expression research. 

PMID- 24311062
TI  - Agomelatine: an agent against anhedonia and abulia?
AB  - Anhedonia and abulia are syndromes often presented as components of various
      psychiatric and neurological disorders, including depression, schizophrenia,
      stroke, multiple sclerosis and brain injury. On the basis of the hypothesis that
      alterations in the dopaminergic motivational system might be involved in the
      etiopathogenesis of these clinical phenomena, the antidepressant agomelatine is a
      highly interesting candidate substance for their treatment because of its
      indirect dopaminergic effects resulting from its melatoninergic and partial anti
      serotoninergic properties. Systematic clinical studies are urgently needed to
      test the hypothesis that agomelatine might be a clinically useful and versatile
      anti-anhedonic and/or anti-abulic substance. 

PMID- 24311063
TI  - Very early reduction in efficacy of botulinum toxin therapy for cervical dystonia
      in patients with subsequent secondary treatment failure: a retrospective
      analysis.
AB  - The objective of this study was to estimate the probability of development of
      partial secondary treatment failure (PSTF) in patients with cervical dystonia
      (CD) who had been treated over up to 9 years with repetitive intramuscular
      injections of botulinum neurotoxin type A (BoNT/A). The temporal course of
      treatment response in patients in whom PSTF was detected retrospectively was
      compared to patients with a normal clinical response. For this purpose, charts of
      all CD patients treated in our outpatient clinic between 1988 and 2001 were
      retrospectively analyzed. Extracted data included time of all injections, dose
      per visit, disease severity measured by TSUI scores, and time of determination of
      neutralizing antibodies. Final data analysis using a special formal definition of
      PSTF was based on charts of 568 patients having exclusively been treated with
      abobotulinumtoxinA. PSTF onset was observed in our CD cohort during the entire
      treatment period analyzed, with no clustering at any time point. Probability to
      develop PSTF was 14.5 % in 9 years. Thus, mean PSTF incidence was 1.6 % per year.
      The mean TSUI score of patients with retrospectively defined PSTF (n = 33) became
      already significantly worse after the second injection when compared with the
      group without PSTF (n = 535). Our data indicate that clinical response in
      patients developing PSTF later on differs from that of patients without PSTF
      already very early in the course of botulinum neurotoxin type A treatment, and
      that PSTF remains undetected at this early stage. Reduced response may therefore
      be present in a number of CD patients who think they still respond normally to
      continuous BoNT/A treatment. 

PMID- 24311064
TI  - Reminiscences, collaborations and reflections.
AB  - This is a personal account by a semi old-timer who completed his official term as
      a professor of plant biochemistry at Nagoya University in Japan in 1992. My
      university student life began soon after the World War II (1948). I shared the
      hardships of many in my age group, in that life was difficult during my college
      years. I was fortunate to have the opportunity of studying in the USA on a
      Fulbright scholarship first at Purdue University (1955-1956), and then at the
      University of California, Berkeley (1956-1957). My graduate study and
      postdoctoral training in the new world were vitally refreshing and stimulating,
      which gave me the impetus for becoming a natural scientist associated with
      academic institutions. Consciously and subconsciously I was impressed by the
      friendly and liberal atmosphere surrounding young students as well as senior
      scholars in the United States. But more importantly, I was inspired by the
      critical and competitive minds prevailing among these people.The appointment as a
      biochemist at the International Rice Research Institute (IRRI) in the Philippines
      (1962-1964) was the real start of my professional career. The work was continued
      upon my return to Nagoya to become a staff member of the Research Institute for
      Biochemical Regulation (1964-1992). Throughout the years, my major research
      interest has covered photosynthesis as a whole, involving photosynthetic CO2
      fixation (RuBisCO), carbohydrate metabolism, e.g. starch biosynthesis and
      breakdown (alpha-amylase), and metabolic regulation, which are interrelated in
      the basic metabolism of plant cells.I shall briefly describe in this article
      highlights from my studies and discoveries made and I shall also discuss their
      possible significance in plant metabolism, with the hope that it does not
      contradict my sense of humility: They are (a) discovery of ADPG in plants and its
      role in starch biosynthesis; (b) structure-function relationship of RuBisCO
      proteins, in particular on heterologous recombination of their subunits of plant
      type enzyme molecules derived from the prokaryotic photosynthetic bacteria; (c)
      molecular evolution of RuBisCO genes; (d) mode of actions (formation,
      intracellular transport and secretion) of rice seed alpha-amylase and its
      structural characteristics (distinctive glycosylation), and (e) DNA methylation
      and regulatory mechanism of photosynthesis gene expression in plastids
      (amyloplasts). In each step of my research, I shared joy, excitement,
      disappointment, and agony with my colleagues, an experience that may be common to
      all researchers. Although it is now becoming well recognized among the scientific
      community in Japan, I want to point out that interaction of multinational
      scientific minds in the laboratory produces a vital and creative atmosphere for
      performance of successful research. I experienced and realized this important
      fact in my earlier days in the USA and the Philippines. Inasmuch as I believe
      that this is the most crucial element for any research laboratory to possess, I
      fondly remember the friendships gained with numerous overseas visitors and
      collaborators who have contributed immensely to our work. 

PMID- 24311066
TI  - Membrane barriers and Mehler-peroxidase reaction limit the ascorbate available
      for violaxanthin de-epoxidase activity in intact chloroplasts.
AB  - The presence of an acidic lumen and the xanthophylls, zeaxanthin and
      antheraxanthin, are minimal requirements for induction of non-radiative
      dissipation of energy in the pigment bed of Photosystem II. We recently reported
      that ascorbate, which is required for formation for these xanthophylls, also can
      mediate the needed lumen acidity through the Mehler-peroxidase reaction [Neubauer
      and Yamamoto (1992) Plant Physiol 99: 1354-1361]. It is demonstrated that in non
      CO2-fixing intact chloroplasts and thylakoids of Lactuca sativa, L. c.v. Romaine,
      the ascorbate available to support de-epoxidase activity is influenced by
      membrane barriers and the ascorbate-consuming Mehler-peroxidase reaction. In
      intact chloroplasts, this results in biphasic kinetic behavior for light-induced
      de-epoxidation. The initial relatively high activity is due to ascorbate
      preloaded into the thylakoid before light-induction and the terminal low activity
      due to limiting ascorbate from the effects of chloroplast membranes barriers and
      a light-dependent process. A five-fold difference between the initial and final
      activities was observed for light-induced de-epoxidation in chloroplasts pre
      incubated with 120 mM ascorbate for 40 min. The light-dependent activity is
      ascribed to the competitive use of ascorbic acid by ascorbate peroxidase in the
      Mehler-peroxidase reaction. Thus, stimulating ascorbic peroxidase with H2O2
      transiently inhibited de-epoxidase activity and concomitantly increased
      photochemical quenching. Also, the effects inhibiting ascorbate peroxidase with
      KCN, and the KM values for ascorbate peroxidase and violaxanthin de-epoxidase of
      0.36 and 3.1 mM, respectively, support this conclusion. These results indicate
      that regulation of xanthophyll-dependent non-radiative energy dissipation in the
      pigment bed of Photosystem II is modulated not only by lumen acidification but
      also by ascorbate availability. 

PMID- 24311065
TI  - Molecular biology of C4 phosphoenolpyruvate carboxylase: Structure, regulation
      and genetic engineering.
AB  - Three to four families of nuclear genes encode different isoforms of
      phosphoenolpyruvate (PEP) carboxylase (PEPC): C4-specific, C3 or etiolated, CAM
      and root forms. C4 leaf PEPC is encoded by a single gene (ppc) in sorghum and
      maize, but multiple genes in the C4-dicot Flaveria trinervia. Selective
      expression of ppc in only C4-mesophyll cells is proposed to be due to nuclear
      factors, DNA methylation and a distinct gene promoter. Deduced amino acid
      sequences of C4-PEPC pinpoint the phosphorylatable serine near the N-terminus, C4
      specific valine and serine residues near the C-terminus, conserved cysteine,
      lysine and histidine residues and PEP binding/catalytic sites. During the PEPC
      reaction, PEP and bicarbonate are first converted into carboxyphosphate and the
      enolate of pyruvate. Carboxyphosphate decomposes within the active site into Pi
      and CO2, the latter combining with the enolate to form oxalacetate. Besides
      carboxylation, PEPC catalyzes a HCO3 (-)-dependent hydrolysis of PEP to yield
      pyruvate and Pi. Post-translational regulation of PEPC occurs by a
      phosphorylation/dephosphorylation cascade in vivo and by reversible enzyme
      oligomerization in vitro. The interrelation between phosphorylation and
      oligomerization of the enzyme is not clear. PEPC-protein kinase (PEPC-PK), the
      enzyme responsible for phosphorylation of PEPC, has been studied extensively
      while only limited information is available on the protein phosphatase 2A capable
      of dephosphorylating PEPC. The C4 ppc was cloned and expressed in Escherichia
      coli as well as tobacco. The transformed E. coli produced a
      functional/phosphorylatable C4 PEPC and the transgenic tobacco plants expressed
      both C3 and C4 isoforms. Site-directed mutagenesis of ppc indicates the
      importance of His(138), His(579) and Arg(587) in catalysis and/or substrate
      binding by the E. coli enzyme, Ser(8) in the regulation of sorghum PEPC.
      Important areas for further research on C4 PEPC are: mechanism of transduction of
      light signal during photoactivation of PEPC-PK and PEPC in leaves, extensive use
      of site-directed mutagenesis to precisely identify other key amino acid residues,
      changes in quarternary structure of PEPC in vivo, a high-resolution crystal
      structure, and hormonal regulation of PEPC expression. 

PMID- 24311067
TI  - Hypothesis for the evolution of three-helix Chl a/b and Chl a/c light-harvesting
      antenna proteins from two-helix and four-helix ancestors.
AB  - The nuclear-encoded Chl a/b and Chl a/c antenna proteins of photosynthetic
      eukaryotes are part of an extended family of proteins that also includes the
      early light-induced proteins (ELIPs) and the 22 kDa intrinsic protein of PS II
      (encoded by psbS gene). All members of this family have three transmembrane
      helices except for the psbS protein, which has four. The amino acid sequences of
      these proteins are compared and related to the three-dimensional structure of pea
      LHC II Type I (Kuhlbrandt and Wang, Nature 350: 130-134, 1991). The similarity of
      psbS to the three-helix members of the family suggests that the latter arose from
      a four-helix ancestor that lost its C-terminal helix by deletion. Strong internal
      similarity between the two halves of the psbS protein suggests that it in turn
      arose as the result of the duplication of a gene encoding a two-helix protein.
      Since psbS is reported to be present in at least one cyanobacterium, the
      ancestral four-helix protein may have been present prior to the endosymbiotic
      event or events that gave rise to the photosynthetic eukaryotes. The Chl a/b and
      Chl a/c antenna proteins, and the immunologically-related proteins in the
      rhodophytes may have had a common ancestor which was present in the early
      photosynthetic eukaryotes, and predated their division into rhodophyte,
      chromophyte and chlorophyte lineages. The LHC I-LHC II divergence probably
      occurred before the separation of higher plants from chlorophyte algae and
      euglenophytes, and the different Types of LHC I and LHC II proteins arose prior
      to the separation of angiosperms and gymnosperms. 

PMID- 24311068
TI  - A transcription unit for the Rieske FeS-protein and cytochrome b in Chlorobium
      limicola.
AB  - A transcription unit petCB from Chlorobium limicola is described. The leading
      gene petC codes for a Rieske FeS-protein of 19.04 kDa with 181 amino acid
      residues. The following gene petB codes for a cytochrome b of 47.48 kDa with 428
      amino acid residues. The transcription unit lacks a third gene pet-A for
      cytochrome c 1 or-f, which is found in the fbc-operons of gram-negative bacteria.
      In the derived amino acid sequence for the Rieske FeS-protein the four cysteines
      and the 2 histidines are conserved in the peptides binding the 2Fe2S-cluster,
      although the redox potential of the cluster is about 150 mV more negative in
      Chlorobium. The gene for cytochrome b includes the coding region for an N
      terminal, positively charged extension which is typical for Chlorobium. The gene
      is not split into two parts for cytochrome b 6 and subunit IV. However, a
      fourteenth amino acid between the two histidines in the fourth, putative
      transmembrane helix, and the lack of an eighth transmembrane helix at the C
      terminus, among other features, clearly resemble the cytochrome b 6 f-complexes.
      Therefore, the separation into b 6 f- and bc 1-type complexes during evolution
      must have occurred before the split of the gene. 

PMID- 24311069
TI  - Sulfide-quinone and sulfide-cytochrome reduction in Rhodobacter capsulatus.
AB  - The reduction by sulfide of exogenous ubiquinone is compared to the reduction of
      cytochromes in chromatophores of Rhodobacter capsulatus. From titrations with
      sulfide values for Vmax of 300 and 10 MUmoles reduced/mg bacteriochlorophyll a.h,
      and for Km of 5 and 3 MUM were estimated, for decyl-ubiquinone-and cytochrome c
      reduction, respectively. Both reactions are sensitive to KCN, as has been found
      for sulfide-quinone reductase (SQR) in Oscillatoria limnetica, which is a
      flavoprotein. Effects of inhibitors interfering with quinone binding sites
      suggest that at least part of the electron transport from sulfide in R.
      capsulatus employs the cytochrome bc 1-complex via the ubiquinone pool. 

PMID- 24311070
TI  - Isolation and characterization of the ccmM gene required by the cyanobacterium
      Synechocystis PCC6803 for inorganic carbon utilization.
AB  - A high CO2-requiring mutant of Synechocystis PCC6803 (G3) capable of Ci transport
      but unable to utilize the intracellular Ci pool for photosynthesis was
      constructed. A DNA clone of 6.1 kbp that transforms the G3 mutant to the wild
      type phenotype was isolated from a Synechocystis PCC6803 genomic library.
      Complementation test with subclones allocated the mutation site within a DNA
      fragment of 674 bp nucleotides. Sequencing analysis of the mutation region
      elucidated an open reading frame encoding a 534 amino-acid protein with a
      significant sequence homology to the protein coded by the ccmN gene of
      Synechococcus PCC7942. The ccmM-like gene product of Synechocystis PCC6803
      contains four internal repeats with a week similarity to the rbcS gene product.
      An open reading frame homologous to the ccmN gene of Synechococcus PCC7942 was
      found downstream to the ccmM-like gene. As opposed to the Synechococcus PCC7942
      ccmM and ccmN genes located 2 kbp upstream to, and oriented in the same direction
      as, the rbc operon, the ccm-like genes in Synechocystis PCC6803 are not located
      within 22 kbp upstream to the rbcL gene of the Rubisco operon. Thus, despite the
      resemblance in clustering of the ccmM and ccmN genes in both cyanobacterial
      species, the difference in their genomic location relative to the rbc genes
      demonstrates variability in structural organization of the genes involved in
      inorganic carbon acquisition. 

PMID- 24311071
TI  - Singlet oxygen production in thylakoid membranes during photoinhibition as
      detected by EPR spectroscopy.
AB  - Exposure of isolated spinach thylakoids to high intensity illumination
      (photoinhibition) results in the well-characterized impairment of Photosystem II
      electron transport, followed by degradation of the D1 reaction centre protein. In
      the present study we demonstrate that this process is accompanied by singlet
      oxygen production. Singlet oxygen was detected by EPR spectroscopy, following the
      formation of stable nitroxide radicals from the trapping of singlet oxygen with a
      sterically hindered amine TEMP (2,2,6,6-tetramethylpiperidine). There was no
      detectable singlet oxygen production during anaerob photoinhibition or in the
      presence of sodium-azide. Comparing the kinetics of the loss of PS II function
      and D1 protein with that of singlet oxygen trapping suggests that singlet oxygen
      itself or its radical product initiates the degradation of D1. 

PMID- 24311072
TI  - Sensitivity of the relative Fpl level of chlorophyll fluorescence induction in
      leaves to the heat stress.
AB  - The (Fpl-Fo)/Fv value of the fluorescence induction curve is shown to be a more
      suitable parameter to detect a wider range of heat stress damage to thylakoid
      membranes as compared to quantities t 1/2 (time of fluorescence rise from Fo to
      (Fo+Fm)/2 level) and % MathType!MTEF!2!1!+-%
      feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn%
      hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr%
      4rNCHbGeaGak0Jf9crFfpeea0xh9v8qiW7rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0
      yqaqpepae9pg0FirpepeKkFr0xfr-x% fr
      xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaWaa0aaaeaacq%
      aHepaDaaaaaa!39D5!?[?overline ?tau ?] (the fluorescence induction time defined as
      the area above the induction curve normalized to Fv=1). A method for exact and
      automatic Fpl determination is presented.A break point in the quality and
      behaviour of the fluorescence induction curve of barley leaves incubated at 49
      degrees C was reached at the moment (about 240 s) when the transformation of PS
      II active (QB-reducing) to PS II inactive (QB-non-reducing) centres was
      completed. The meaning of the standard Fv and Fv/Fm parameter was then
      changed.The method of Fpl determination described here may help to increase the
      analytical value of the standard chlorophyll fluorometers. 

PMID- 24311073
TI  - Ribosylzeatin and zeatin in tobacco crown gall tissue.
AB  - Cytokinins were extracted from two cultures of tobacco crown gall tumor tissue:
      an unorganized tissue and a teratoma which produced leafy shoots. On Sephadex LH
      20 column chromatography, extracts of both types of tissue yielded two peaks of
      cytokinin activity with elution volumes similar to ribosylzeatin and zeatin.
      Ribosylzeatin and zeatin were detected and quantified by coupled gas
      chromatography - mass spectrometry selected ion monitoring (GC/MS SIM),
      comparable quantities being found in the two extracts. Full mass spectral
      evidence for the presence of ribosylzeatin in both tissues was obtained. No
      evidence was found for the presence of N(6)-(Delta(2)-isopentenyl)adenosine
      (i(6)Ade) or N(6)-(Delta(2)-isopentenyl)adenine (i(6)Ade) although these
      compounds have been reported to occur in cytokinin-habituated tobacco callus
      tissues. 

PMID- 24311074
TI  - Multistage disruption of protoplasts by dikegulac.
AB  - Dikegulac (2,3:4,6 di-o-isopropylidine-2-keto-I-gulonate) is a growth regulator
      used to differentially kill terminal apices, and it analogously inhibits basic
      metabolic functions in dividing cells, but not stationary cells, in suspension
      culture. This report demonstrates an analogous situation in isolated tobacco
      protoplasts. At the lowest concentrations, dikegulac partially suppresses
      division of the protoplasts. Higher concentrations are required to produce visual
      cytoplasmic damage to the protoplasts, which probably first occurs at the level
      of the plasmalemma, as the vacuoles can be released intact. Later, tonoplast
      disruption occurs. 

PMID- 24311075
TI  - Oxygen inhibition of photosynthesis in the C4 species Amaranthus graecizans L.
AB  - In the C4 plant, Amaranthus graecizans, increasing [O2] from 2% up to 100%
      inhibited photosynthesis, quantum yield, and the carboxylation efficiency, and
      increased the CO2 compensation point (Gamma) from 2 to about 12 MUl/l. The O2
      inhibition of photosynthesis was fully reversible. When changing from 2.5 to 40%
      O2 and vice versa, about 1 h was required for full equilibration with an O2
      inhibition of 18%; whereas in wheat, a C3 species, inhibition of photosynthesis
      and its reversal occurs within minutes after changing [O2], resulting in 63%
      inhibition of photosynthesis by 45% O2. These differences in O2 inhibition
      between a C4 and C3 species can be explained by high diffusive resistance across
      bundle-sheath cells of C4 plants and the increased CO2/O2 ratio in bundle-sheath
      cells which is the consequence of the C4 cycle. In A. graecizans, Gamma increased
      with increasing [O2] but tended to reach a maximum at relatively high O2 levels.
      The lack of a linear increase in Gamma as previously observed for C3 species
      indicates that a considerable amount of photorespired CO2 may be re-fixed with
      increasing levels of O2. In comparison to previous reports with other C4 species,
      photosynthesis of A. graecizans shows greater sensitivity to O2, with a
      noticeable inhibition occurring with shifts from 2 to 21% O2. A. graecizans has
      characteristics of other C4 species with respect to Kranz anatomy, localization
      of PEP carboxylase in mesophyll cells and RuBP carboxylase in bundle-sheath
      cells, and little fractionation among carbon isotopes during CO2 fixation. The
      basis for the higher sensitivity of photosynthesis of A. graecizans to O2 may be
      based upon a lower diffusive resistance of gases across bundle-sheath cells than
      in some other C4 species. 

PMID- 24311076
TI  - An improved procedure for the isolation and purification of protoplasts from
      carrot suspension culture.
AB  - A procedure is reported for the rapid and highly reproducible isolation of
      protoplasts from carrot suspension culture. The method utilizes Onozuka R 10
      cellulase which has been purified by chromatography on Sephadex G75. Protoplast
      isolation, using this procedure, is quantitative and complete within 1 to 1.5 h.
      Intact protoplasts were separated from broken ones and other cellular debris by
      application of a polyethylene glycol/dextran two-phase system. The protoplasts
      isolated in this manner lack any detectable cell wall and are greater than 95%
      viable when assayed using fluorescein diacetate. It is concluded that such
      protoplasts are highly suitable for biochemical studies. 

PMID- 24311077
TI  - Protein deficient chloroplast ribosomes in a yellow mutant of Chlamydomonas
      reinhardii.
AB  - Ribosomes and ribosomal proteins from wild-type and a yellow mutant of
      Chlamydomonas reinhardii were analyzed and compared by two-dimensional gel
      electrophoresis. The mixothrophically grown yellow-76 mutant differs from wild
      type cells in lowered chlorophyll content and photosynthetic activity per
      chlorophyll unit. The latter is connected with the decreased activity of the
      ribulose-I,5-diphosphate-carboxylase enzyme. Analytical ultracentrifugation of
      cell extracts shows a normal amount of free 70S ribosomes and 50S subunit in the
      mutant cells. Two-dimensional gel electrophoresis shows considerable alterations
      in the protein composition of the 70S ribosomes of the mutant. Two proteins are
      absent from the electrophoretograms of the yellow-76 mutant, and seven proteins
      are present in reduced amounts. The genetical analysis shows a Mendelian pattern
      of inheritance, indicating that protein alterations presumably are localized in
      nuclear DNA. 

PMID- 24311078
TI  - Broad-range effects of ionophore X-537A on pollen tubes of Lilium longiflorum.
AB  - The effects of the broad-range cationophore X-537A on pollen tubes of Lilium
      longiflorum were investigated, using both light and electron microscopy. Pollen
      tube growth is completely inhibited within 30 min after the application of 5.10(
      5) M ionophore X-537A; cytoplasmic streaming is stopped only after 60 min of
      ionophore treatment. Ultrastructurally, X-537A effects are a vacuolation of Golgi
      cisternae and a general vacuolation. The wall is thickened at the very tip.
      Coated vesicles and coated regions are enriched close to and at the plasma
      membrane. The results indicate that pollen tube tip growth needs a specific ion
      distribution. 

PMID- 24311079
TI  - Cell-free translation of exogenous mRNA in extracts from dry pea primary axes.
AB  - Extracts from the primary axes of dry pea (Pisum sativum L.) seeds are able to
      perform an initiation-dependent translation of exogenous mRNA. SDS polyacrylamide
      gel electrophoresis of the products synthesized under direction of alfalfa mosaic
      virus RNA (AMV-RNA) and tobacco mosaic virus RNA (TMV-RNA) shows that the
      fidelity of translation in this pea system is at least as high as in a wheat
      embryo cell-free protein synthesizing system. The endogenous messengers are also
      efficiently translated in extracts from the primary axes of pea seeds. The direct
      translation of these messengers in a homologous cell-free system may be of
      interest for a study of the products coded for by the long-lived messengers
      present in this plant. 

PMID- 24311080
TI  - Botanical aspects of cell-free protein synthesizing systems from cereal embryos.
AB  - Some botanical aspects of cell-free protein synthesizing systems from cereal
      embryos have been investigated. The composition of the starting material
      determines both the stability and translation fidelity of the cell-free extracts.
      The active components of the extracts originate exclusively from the primary
      axes. Contamination with scutellum fragments does not affect the initial activity
      but results in a reduced stability. The presence of endosperm particles in the
      starting material leads to a strong decrease of the overall activity of the
      extracts and a loss of the capacity to synthesize large polypeptides. 

PMID- 24311081
TI  - In vitro binding of riboflavin to subcellular particles from maize coleoptiles
      and Cucurbita hypocotyls.
AB  - Saturable and reversible in vitro binding of [(14)C]riboflavin was found to occur
      on subcellular, sedimentable particles from maize coleoptiles and Cucurbita
      hypocotyls. The KD was ca. 6 MUM, the pH optimum was near 6.0, and the number of
      binding sites amounted to 0.1-0.5 MUM on a fresh-weight basis. When the reducing
      agent dithionite was present, riboflavin binding increased-the KD was 2.5 MUM,
      and the pH optimum above 8.0. The binding was specific: flavin mononucleotide
      (FMN) and flavin adenosine-dinucleotide (FAD) bound less tightly to these sites
      than riboflavin and another major soluble flavin, the previously described
      riboflavin-analog "FX", occurring in grass coleoptiles. These flavin-binding
      sites were localized on vesicles derived from plasmalemma and endoplasmic
      reticulum by analyzing sucrose and metrizamide density gradients and marker
      enzymes. 

PMID- 24311082
TI  - Development of nodules of Glycine max infected with an ineffective strain of
      Rhizobium japonicum.
AB  - Bacteroids in ineffective (nitrogenase negative) nodules of Glycine max, infected
      with Rhizobium japonicum 61-A-24, as compared to those in effective nodules are
      characterized by reduced specific activities of alanine dehydrogenase to 15%, of
      3-hydroxybutyrate dehydrogenase to 50%, and an increase of glutamine synthetase
      to 400%. In the plant cytoplasm of ineffective nodules, glutamine synthetase
      activity is reduced to 10-30%, glutamate dehydrogenase to 50-70%, and the
      aspartate aminotransferase and alanine aminotransferase are enhanced to 120-200%,
      depending on the age of the nodules. The total pool of soluble amino acids is
      reduced to 52 MUmol per g nodule fresh weight, as compared to 186 MUmol in
      effective nodules, with a replacement of asparagine (42 mol% of the amino acids)
      by an unknown amino compound. This compound is absent in nitrogenase, repressed
      and derepressed, free-living Rhizobium japonicum cells and in the uninfected root
      tissue. In nitrogenase derepressed, as compared to the repressed free-living
      cells of Rhizobium japonicum 61-A-101, arginine shows the most obvious change
      with a reduction to less than one tenth. The ultrastructure of the ineffective
      nodule is different from the effective organ even in the early stages. The
      membrane envelopes of the infection vacuoles are decomposing in heavily infected
      cells within 18 to 20 d after infection. In lightly infected cells very large
      vacuoles develop with only a few bacteroids inside. No close associations of
      cristae-rich mitochondria with amyloplasts are observed as in effective nodules.
      The uninfected cells keep their large starch granules even 40 d after infection.
      Some poly-beta-hydroxybutyrate accumulation in the bacteroids is observed but
      only in the early stages, and it is almost absent in old nodules (40 d). At this
      age the infected cells are obviously compressed by uninfected cells, whereas in
      effective nodules with nitrogenase activity and leghaemoglobin formation, the
      infected cells have a much higher osmotic pressure than the neighbouring
      uninfected cells. 

PMID- 24311083
TI  - Physiological factors determining formation of plastocyanin and plastidic
      cytochrome c-553 in Scenedesmus.
AB  - Physiological conditions necessary for the formation of plastocyanin and the
      concurrent cessation of cytochrome c-553 formation were studied in cells of
      copper-deficient Scenedesmus acutus after the addition of copper. Plastocyanin is
      formed after a lag-phase, leaving constant the content of plastidic cytochrome c
      553. Therefore, the concentration of plastocyanin per cell increases and the
      concentration of cytochrome c-553 decreases during growth. Formation of
      plastocyanin during the induction period studied is dependent on light intensity.
      In the dark, there is a 90% inhibition, whereas under light intensities above 50
      Wm(-2), a ratio of 1.3 molecules plastocyanin per 1,000 molecules chlorophyll is
      attained.Plastocyanin formations is inhibited by the uncoupler carbonylcyanide-p
      trifluoromethoxy phenylhydrazone (FCCP), but not by moderate concentrations of 3
      [3',4'-dichlorophenyl]-1,1-dimethylurea (DCMU), and by keeping the algae under a
      nitrogen atmosphere without CO2. Concurrently, the cultures treated with FCCP
      show a decreased endogenous ATP level. The ATP is necessary for plastocyanin
      formation. 

PMID- 24311084
TI  - Induction of transfer-cell formation by iron deficiency in the root epidermis of
      Helianthus annuus L.
AB  - Helianthus annuus L. responds to iron deficiency by forming a thickened cortex
      and abundant root hairs in a zone near the root apex that corresponds to the
      primary developmental stage. Cytological investigations revealed that within 24
      to 48 h of iron deficiency most of the peripheral cells differentiate into
      transfer cells. The wall labyrinth is always situated on the peripheral walls
      that face the external medium. The cytoplasm of these cells is characterized by
      numerous mitochondria, extensive rough endoplasmic reticulum, and large
      leucoplasts containing protein bodies. These observations are discussed in
      relation to the fact that Helianthus, as an "iron efficient" plant, responds
      physiologically to iron deficiency by extrusion of H(+), production of reducing
      substances, and a steep increase in the uptake efficiency of Fe. 

PMID- 24311085
TI  - Production of higher levels of trigonelline by cell cultures of Trigonella foenum
      graecum than by the differentiated plant.
AB  - Callus cultures of Trigonella foenum-graecum contained 3 to 4 times more
      trigonelline than the seeds of this plant and 12 to 13 times more than the roots
      and shoots. Even higher levels of this alkaloid were produced by suspension
      cultures. This high productivity was maintained during successive subculturing of
      calli and cell suspensions for eight months. Thus, trigonelline is to be added to
      the group of the few metabolites whose synthesis in cell cultures exceeds its
      production in the differentiated plants. Media that had supported the growth of
      suspension cultures contained one third or more of the total alkaloid, whereas
      media of callus cultures contained about one tenth of this substance.
      Trigonelline accumulated in callus and suspension cultures with aging. Raising
      the level of nicotinic acid in the nutrient medium resulted in some increase of
      trigonelline production by the culture. 

PMID- 24311086
TI  - Water permeability of Betula periderm.
AB  - The water permeability of periderm membranes stripped from mature trees of Betula
      pendula Roth was investigated. The diffusion of water was studied using the
      system water/membrane/water, and transpiration was measured using the system
      water/membrane/water vapor. Betula periderm consists of successive periderm
      layers each made up of about 5 heavily suberized cell layers and a varying number
      of cell layers that are little suberized, if at all. It is shown that these
      layers act as resistances in series. The permeability coefficient of the
      diffusion of water (P d) can be predicted with 79% accuracy from the reciprocal
      of the membrane weight (x in mg cm(-2)) by means of the linear equation P
      d=14.69.10(-7) x-0.73.10(-7). For example, the P d of a periderm membrane having
      a weight of 10 mg cm(-2) (approx. 250 MUm thick) is 7.4.10(-8) cm s(-1), which is
      comparable to the permeability of cuticles. This comparison shows that on a basis
      of unit thickness, Betula periderm is quite permeable to water as cuticles have
      the same resistance with a thickness of only 0.5 to 3 MUm. It is argued that this
      comparatively high water permeability of birch periderm is due to the fact that
      middle lamellae and the primary walls of periderm cells are not at all, or only
      incompletely suberized and, therefore, form a hydrophilic network within which
      the water can flow. This conclusion is based on the following observations: (1)
      Middle lamellae and primary walls stain strongly with toluidine blue, which shows
      them to be polar. (2) If silver ions are added as tracer for the flow of water,
      they are found only in the middle lamellae, primary walls, and in plasmodesmata,
      while no silver can be detected in the suberized walls. (3) Permeability
      coefficients of transpiration strongly depend on water activity. This shows
      conclusively that water flows across Betula periderm via a polar pathway. It is
      further argued that liquid continuity is likely to be maintained under all
      physiological conditions in the network formed by middle lamellae and primary
      walls. On the other hand, the lumina of periderm cells, intercellular air spaces
      in the lenticels, and even the pores in the suberized walls (remainders of
      plasmodesmata) will drain at a humidity of 95% and below. Due to the presence of
      intercellulars the permeability coefficient of lenticels is much greater than
      that of the periderm. A substantial amount of the total water, therefore, flows
      as vapor through lenticels even though they cover only 3% of the surface. 

PMID- 24311087
TI  - Blue-light-induced cortical fiber reticulation concomitant with chloroplast
      aggregation in the alga Vaucheria sessilis.
AB  - Point illumination with low-intensity blue light induces the chloroplasts and
      other organelles, which normally stream in the cytoplasm of Vaucheria sessilis
      (Vauch.) D.C. (Xanthophyceae), to aggregate in the illuminated region of the
      cell. Aggregation is passive and results from the "trapping" of the organelles as
      they stream into the blue light. Prior to illumination, longitudinal fibers along
      which the organelles appear to move, can readily be seen through a light
      microscope fitted with differential interference contrast optics. Upon actinic
      irradiation, these fibers appear to become destabilized, branching and forming a
      cortical fiber reticulum in the light. The reticulation process always precedes
      chloroplast aggregation. Aggregation itself occurs after a lag period which is
      inversely related to fluence rate. The lag period at high fluence rates (>400 mW
      m(-2)) may be as short as 20 s. Studies of wavelength dependence show that
      wavelengths near 480 nm are maximally effective while those longer than 530 nm
      are inactive. 

PMID- 24311088
TI  - Actin and cortical fiber reticulation in the siphonaceous alga Vaucheria
      sessilis.
AB  - Since light-induced organellae aggregation in the siphonaceous alga Vaucheria
      sessilis (Vauch.) D.C. is accompanied by the formation of a cortical fiber
      reticulum in the light, we proposed that this process of reticulation might be
      causally related to aggregation (Blatt and Briggs, 1980). In this paper we report
      the tentative identification of actin filaments and filament bundles in the
      cortical cytoplasm of V. sessilis, and present additional evidence, obtained
      using the inhibitors cytochalasin B and phalloidin and indicating that
      aggregation in response to low-intensity point irradiation with blue light is
      dependent upon the formation of a cortical fiber reticulum. Phalloidin stabilized
      the cortical fibers, preventing both reticulum formation and organelle
      aggregation in blue light. Cytochalasin B partially destabilized the cortical
      fibers to the extent of permitting light-induced reticulum formation and
      organelle aggregation in the light in the presence of phalloidin. 

PMID- 24311089
TI  - Gibberellins in mature apple seeds - contaminants?
AB  - Evidence is presented that gibberellins A4 and A7, previously identified (Sinska,
      I., Lewak, St., Gaskin, P., MacMillan, J., Planta 114, 359-364, 1973) in extracts
      of mature apple (Pyrus malus L.) seeds, were present primarily as contaminants.
      The facts supporting this conclusion are: a) the ratio of GA4 to GA7 was similar
      to that of a standard mixture; b) the concentrations were extremely high; and c)
      the ratio of GA4 to GA7 did not change during stratification, as had been
      reported when extracts were bioassayed (Sinska, I., and Lewak, St., Physiol. Veg.
      8, 661-667, 1970). 

PMID- 24311090
TI  - Comments on the paper by F.G. Dennis, G.C. Martin, P. Gaskin, and J. MacMillan:
      Gibberellins in mature apple seeds-contaminants?

PMID- 24311091
TI  - Identification of chemical oviposition stimulants from rice grain forSitophilus
      zeamais motschulsky (Coleoptera, Curculionidae).
AB  - Chemical components stimulating oviposition bySitophilus zeamais in rice grain
      were isolated from rice bran and were found to be a mixture of ferulates,
      diglycerides, and free sterols. Oviposition preference of the species can be
      induced by synergistic action of these compounds. 

PMID- 24311092
TI  - Trap trees for elm bark beetles : Augmentation with pheromone baits and
      chlorpyrifos.
AB  - European elm bark beetles,Scolytus multistriatus (Marsh.), were strongly
      attracted to American elms,Ulmus americana L., baited with theS. multistriatus
      attractant, multilure, or killed by injection of the arboricide, cacodylic acid;
      a combination of the two treatments was most attractive. Comparisons of beetle
      catches on sticky bands affixed to the trees with samples of bark from the same
      trees showed that the number of beetles landing on cacodylic acid-treated trees
      was approximately 40 times greater than the number boring into them. Spraying the
      bark with the insecticide chlorpyrifos had no direct effect on attraction. No
      live bark beetle brood was found in trees that had been treated with cacodylic
      acid or chlorpyrifos, but trees that were only baited or left untreated (check)
      were attacked, killed, and colonized. We suggest that the contribution of the
      cacodylic acid trap tree technique to Dutch elm disease control will be enhanced
      by baiting treated trees with multilure and spraying their lower boles with 0.5%
      chlorpyrifos. This treatment will eliminate diseased and unwanted elms as
      potential breeding material and kill large numbers of elm bark beetles that might
      otherwise innoculate healthy elms with the Dutch elm disease fungus. 

PMID- 24311093
TI  - Response of northern corn rootworm,Diabrotica barberi Smith and Lawrence, to
      stereoisomers of 8-methyl-2-decyl propanoate.
AB  - The four stereoisomers of 8-methyl-2-decyl propanoate were tested in South Dakota
      for attractiveness to the northern corn rootworm,Diabrotica barberi Smith and
      Lawrence (NCR). Only the 2R,8R configuration was attractive to the NCR.
      Inhibition of the NCR response to 2R,8R occurred when either the 2S,8R or 2S,8S
      isomers were components of the pheromone source. The 2R,8S configuration elicited
      no behavioral activity in the NCR. 

PMID- 24311094
TI  - Phytotoxic properties of nordihydroguaiaretic acid, a lignan fromLarrea
      tridentata (Creosote bush).
AB  - The phytotoxic properties of nordihydroguaiaretic acid (NDGA) isolated from
      creosote bush,Larrea tridentata (Zygophyllaceae), were examined. NDGA
      dramatically reduces the seedling root growth of barnyard grass, green foxtail,
      perennial ryegrass, annual ryegrass, red millet, lambsquarter, lettuce, and
      alfalfa, and reduces the hypocotyl growth of lettuce and green foxtail. It has no
      effect on the germination of lettuce seeds. NDGA almost certainly contributes to
      the observed allelopathic nature of creosote bush. 

PMID- 24311095
TI  - Effect of some floral scents on host finding by thrips (Insecta: Thysanoptera).
AB  - The role of floral scents in host location by flower-dwelling thrips is
      investigated by experiment in the field. The scent of anisaldehyde significantly
      increased the catches of seven species of flower-dwelling thripid, but had no
      significant effect on three species of cereal thripid and one species of flower
      dwelling aeolothripid. The catches of white (without UV) traps were increased by
      a factor of 3.3 to 8.3 in the presence of the scent. 

PMID- 24311096
TI  - Rhodanese in insects.
AB  - Forty-four species of insects were assayed for the presence of rhodanese, an
      enzyme generally considered to be responsible for the detoxification of cyanide.
      Rhodanese was found to be widely distributed in both adults and larvae and was
      not restricted to those species which encounter exogenous cyanide through feeding
      on cyanogenic plants. These results indicate that cyanide detoxification is
      unlikely to be the primary role for rhodanese in insects. 

PMID- 24311097
TI  - Synthesis of kairomonal 2-acylcyclohexane-1,3-dione components of larval
      mandibular glands ofEphestia kuehniella.
AB  - Three components of the larval mandibular glands ofEphestia (=Anagasta)
      kuehniella, 2-(Z,E)-hexadeca-12',14'-dienoylcyclohexane-1,3-dione, 2
      oleoylcyclohexane-1,3-dione, and 2-linoleoylcyclohexane-1,3-dione, have been
      synthesized and shown to be active as kairomones. 

PMID- 24311098
TI  - Volatile fatty acids of frass of certain omnivorous insects.
AB  - The frass of the following omnivorous insects reared on natural and artificial
      diets was analyzed for volatile fatty acids:Blattella germanica, Acheta
      domesticus, Blaberus discoidalis. Acetic, propionic, isobutyric, butyric,
      isovaleric, and valeric acids were identified in all frass samples. The possible
      significance of volatile fatty acids in frass is discussed. 

PMID- 24311099
TI  - Use ofLemna minor L. as a bioassay in allelopathy.
AB  - Investigations in allelopathy often require the use of a bioassay for evaluating
      limited quantities of potentially active growth regulators. A bioassay procedure
      was developed usingL. minor grown in 1.5-ml aliquots of nutrient medium with and
      without allelochemicals in wells of 24-well tissue culture cluster dishes with
      loose-fitting lids. Tests using six replications per treatment with several
      flavonoid compounds and derivatives of coumarin, benzoic acid, and cinnamic acid
      demonstrated that the bioassay was capable of measuring inhibition at levels of
      compound ranging from 50 to 1000 MUmol. Strongly inhibitory treatments were
      visible after 1 or 2 days. After 7 days of growth, frond number, growth rate, and
      dry weight were used to evaluate effects. The bioassay system is relatively
      simple, very sensitive, reproducible, and can be used for testing small amounts
      and dilute concentrations of unknowns which have been separated by
      chromatography. 

PMID- 24311100
TI  - Effects ofSolanum glycoalkaloids on chemosensilla in the Colorado potato beetle :
      A mechanism of feeding deterrence?
AB  - Steroidal glycoalkaloids, found in species of the Solanaceae, elicit bursting
      activity in galeal and tarsal chemosensilla of adult Colorado potato beetles. The
      effect has an average latency of 6-12 sec, depending on the sensillum/alkaloid
      combination. A 20-sec alkaloid treatment is often suffficient to render galeal
      sensilla unresponsive to gamma-aminobutyric acid, normally an effective
      stimulant. The alkaloids have similar effects on galeal sensilla of larval
      Colorado potato beetles and on labellar chemosensilla of the blowfly. It is
      concluded that these compounds act independently of any specialized chemoreceptor
      in the Colorado potato beetle, and that association of the Colorado potato beetle
      with solanaceous plants has not led to evolution of a specific receptor
      forSolanum glycoalkaloids. 

PMID- 24311101
TI  - Differences and similarities in cardenolide contents of queen and monarch
      butterflies in florida and their ecological and evolutionary implications.
AB  - Florida queen butterflies are highly variable in cardenolide content and, in
      three populations studied, contained less cardenolide than did a sample of
      sympatric Florida monarchs. The possibility that queens stored a more potent set
      of cardenolides from their host plants (and therefore were as well protected as
      monarchs, even at lower concentrations) is refuted by Chromatographic analysis of
      wild butterflies, as well as controlled laboratory rearings. It therefore appears
      that, with respect to cardenolides, monarchs are better defended than are queens.
      Consequently, cardenolides are unlikely to explain the apparent shift in Florida
      viceroy mimicry away from resemblance of the monarch, toward mimicry of the
      queen. Other hypotheses to explain this mimetic phenomenon are suggested. Adult
      monarchs exhibit significant negative correlations between the concentration of
      cardenolide stored in their tissues and both body size and weight, whereas queens
      show no such correlations. The implications of these results for the study of
      "metabolic costs" of allelochemic storage are discussed. Chromatographic evidence
      is provided that monarchs do breed in south Florida during the winter months and
      that the likely host plant employed by the population studied wasAsclepias
      curassavica. This represents the first practical application of cardenolide
      "fingerprinting" to identify the larval host plants of wild danaid butterflies. 

PMID- 24311102
TI  - Measuring minimal concentrations of attractants detected by the
      nematodePanagrellus redivivus.
AB  - A simple method for the experimental determination of minimal concentrations of
      attractants detected by the nematodePanagrellus redivivus is described. The
      lowest concentrations of methyl, ethyl, propyl, butyl, and amyl acetate as well
      as the minimal differences in concentrations of these attractants detectable
      byPanagrellus redivivus are presented. 

PMID- 24311103
TI  - Simple and economic syntheses of some (Z)-7- and (Z)-9-alkenyl acetates, and of
      (E,Z)-7,9-dodecadien-1-yl acetate, the sex pheromone of the European grapevine
      moth, using aleuritic acid as a common starting material.
AB  - Short syntheses of (Z)-7-dodecen-1-yl acetate, (Z)-7-tetradecen-1-yl acetate, (Z)
      9-dodecen-1-yl acetate, and (Z)-9-tetradecen-1-yl acetate from 7-hydroxyheptanal
      and 9-oxononanoic acid precursors obtained by oxidative cleavage of easily
      available aleuritic acid are reported. The key step in these syntheses is a
      stereoselective Wittig reaction between aldehyde and alkyl-phosphonium salt.
      Wittig-Horner type reaction of 7-hydroxyheptanal and diethyl
      cyanomethylphosphonate gave the alpha,beta-unsaturated nitrile derivative which
      after protection of the hydroxyl group was reduced to the corresponding aldehyde.
      Wittig reaction of the latter, followed by acetylation, completed the synthesis
      of (E,Z)-7,9-dodecadien-1-yl acetate, the sex pheromone of the European grapevine
      mothLobesia botrana Schiff. 

PMID- 24311104
TI  - Intensification and prolongation of host searching inLeptopilina heterotoma
      (Thomson) (Hymenoptera: Eucoilidae) through a kairomone produced byDrosophila
      melanogaster.
AB  - A chemical cue (kairomone) of the host, larvae ofDrosophila, was found to
      influence patch-time allocation of the parasiteLeptopilina heterotoma. This
      kairomone is soluble in water and chloroform. The kairomone was purified using
      thin-layer chromatography. The concentration of the kairomone increases with an
      increasing number of hosts. The parasites may use presence and concentration of
      the kairomone as cues to determine patch-time allocation. 

PMID- 24311106
TI  - Partial trisomy 1q41-qter and partial trisomy 9pter-9q21.32 in a newborn infant:
      an array CGH analysis and review.
AB  - We report on a girl who presented with distinctive abducted hip and hyperextended
      knee. Cytogenetic analysis detected an extra derivative chromosome resulting from
      a balanced translocation in the mother and 3:1 segregation. Using array
      comparative genomic hybridization (CGH) in combination with conventional high
      resolution GTG banding, we designate the karyotype as 47, XX,
      +der(9)t(1;9)(q41;q21.32)mat, indicating tertiary trisomy of chromosome segments
      1q41-qter and 9pter-9q21.32. A review and genotype-phenotype correlation
      suggested that the patient represented most of the manifestations of duplication
      of chromosome arms 1q and 9p. To our knowledge, a similar case has so far not
      been reported.

PMID- 24311105
TI  - Sexual scripts and sexual risk behaviors among Black heterosexual men:
      development of the Sexual Scripts Scale.
AB  - Sexual scripts are widely shared gender and culture-specific guides for sexual
      behavior with important implications for HIV prevention. Although several
      qualitative studies document how sexual scripts may influence sexual risk
      behaviors, quantitative investigations of sexual scripts in the context of sexual
      risk are rare. This mixed methods study involved the qualitative development and
      quantitative testing of the Sexual Scripts Scale (SSS). Study 1 included
      qualitative semi-structured interviews with 30 Black heterosexual men about
      sexual experiences with main and casual sex partners to develop the SSS. Study 2
      included a quantitative test of the SSS with 526 predominantly low-income Black
      heterosexual men. A factor analysis of the SSS resulted in a 34-item, seven
      factor solution that explained 68% of the variance. The subscales and coefficient
      alphas were: Romantic Intimacy Scripts (alpha = .86), Condom Scripts (alpha =
      .82), Alcohol Scripts (alpha = .83), Sexual Initiation Scripts (alpha = .79),
      Media Sexual Socialization Scripts (alpha = .84), Marijuana Scripts (alpha =
      .85), and Sexual Experimentation Scripts (alpha = .84). Among men who reported a
      main partner (n = 401), higher Alcohol Scripts, Media Sexual Socialization
      Scripts, and Marijuana Scripts scores, and lower Condom Scripts scores were
      related to more sexual risk behavior. Among men who reported at least one casual
      partner (n = 238), higher Romantic Intimacy Scripts, Sexual Initiation Scripts,
      and Media Sexual Socialization Scripts, and lower Condom Scripts scores were
      related to higher sexual risk. The SSS may have considerable utility for future
      research on Black heterosexual men's HIV risk.

PMID- 24311108
TI  - Functional carbo-butadienes: nonaromatic conjugation effects through a 14-carbon,
      24-pi-electron backbone.
AB  - A systematic study of carbo-butadiene motifs not embedded in an aromatic carbo
      benzene ring is described. Dibutatrienylacetylene (DBA) targets R(1)
      ?C(R)?C?C?C(Ph)?C=C?C(Ph)?C?C?C(R)?R(2) are devised, in which R is C=CSiiPr3 and
      R(1) and R(2) are R, H, or 4-X-C6 H4 , with the latter including three known
      representatives (X: H, NMe2 , or NH2 ). The synthesis method is based on the
      SnCl2 -mediated reduction of pentaynediols prepared by early or late divergent
      strategies; the latter allows access to a OMe-NO2 push-pull diaryl-DBA. If R(1)
      and R(2) are H, an over-reduced dialkynylbutatriene (DAB) with two allenyl caps
      was isolated instead of the unsubstituted DBA. If R(1) =R(2) =R, the tetraalkynyl
      DBA target was obtained, along with an over-reduced DBA product with a 12
      membered 1,2-alkylidene-1H2 ,2H2 -carbo-cyclobutadiene ring. X-ray
      crystallography shows that all of the acyclic DBAs adopt a planar trans-transoid
      trans configuration. The maximum UV/Vis absorption wavelength is found to vary
      consistently with the overall pi-conjugation extent and, more intriguingly, with
      the pi-donor character of the aryl X substituents, which varies consistently with
      the first (reversible) reduction potential and first (irreversible) oxidation
      peak, as determined by voltammetry. 

PMID- 24311107
TI  - Polymorphisms of the farnesyl diphosphate synthase gene modulate bone changes in
      response to atorvastatin.
AB  - Although their primary therapeutic indications are different,
      aminobisphosphonates and statins target enzymes in the mevalonate pathway, which
      is critical for bone homeostasis. Previous studies have shown that some
      polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main
      target of aminobisphosphonates, modulate the response to these drugs. In this
      study, we explored whether those single nucleotide polymorphisms (SNPs) also
      influence the changes in bone mineral density (BMD) following therapy with
      statins. Sixty-six patients with coronary heart disease were studied at baseline
      and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs
      of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using
      Taqman assays. The results showed that there was no association between the SNPs
      and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage
      disequilibrium, were associated with changes in hip BMD following atorvastatin
      therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 +/- 0.8
      % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes,
      BMD showed a 2.3 +/- 0.8 % decrease (p = 0.02). Similar results were obtained
      regarding changes of BMD at the femoral trochanter and when alleles at the
      rs11264359 locus were analyzed. However, there was no association between BMD and
      rs17367421 alleles. In conclusion, these results suggest that polymorphisms of
      the FDPS gene may influence the bone response to various drugs targeting the
      mevalonate pathway, including not only aminobisphosphonates but also statins.

PMID- 24311109
TI  - Computational fluid model incorporating liver metabolic activities in perfusion
      bioreactor.
AB  - The importance of in vitro hepatotoxicity testing during early stages of drug
      development in the pharmaceutical industry demands effective bioreactor models
      with optimized conditions. While perfusion bioreactors have been proven to
      enhance mass transfer and liver specific functions over a long period of culture,
      the flow-induced shear stress has less desirable effects on the hepatocytes liver
      specific functions. In this paper, a two-dimensional human liver hepatocellular
      carcinoma (HepG2) cell culture flow model, under a specified flow rate of 0.03
      mL/min, was investigated. Besides computing the distribution of shear stresses
      acting on the surface of the cell culture, our numerical model also investigated
      the cell culture metabolic functions such as the oxygen consumption, glucose
      consumption, glutamine consumption, and ammonia production to provide a fuller
      analysis of the interaction among the various metabolites within the cell
      culture. The computed albumin production of our 2D flow model was verified by the
      experimental HepG2 culture results obtained over 3 days of culture. The results
      showed good agreement between our experimental data and numerical predictions
      with corresponding cumulative albumin production of 2.9 * 10(-5) and 3.0 * 10(-5)
      mol/m(3) , respectively. The results are of importance in making rational design
      choices for development of future bioreactors with more complex geometries.

PMID- 24311111
TI  - Optimal linear combinations of multiple diagnostic biomarkers based on Youden
      index.
AB  - In practice, usually multiple biomarkers are measured on the same subject for
      disease diagnosis. Combining these biomarkers into a single score could improve
      diagnostic accuracy. Many researchers have addressed the problem of finding the
      optimal linear combination based on maximizing the area under ROC curve (AUC).
      Actually, such combined score might have less than optimal property at the
      diagnostic threshold. In this paper, we propose the idea of using Youden index as
      an objective function for searching the optimal linear combination. The combined
      score directly achieves the maximum overall correct classification rate at the
      diagnostic threshold corresponding to Youden index; in other words, it is the
      optimal linear combination score for making the disease diagnosis. We present
      both empirical and numerical searching methods for the optimal linear
      combination. We carry out extensive simulation study to investigate the
      performance of the proposed methods. Additionally, we empirically compare the
      optimal overall classification rates between the proposed combination based on
      Youden index and the traditional one based on AUC and demonstrate a significant
      gain in diagnostic accuracy for the proposed combination. In the end, we apply
      the proposed methods to a real data set.

PMID- 24311110
TI  - Antioxidants and vision health: facts and fiction.
AB  - A number of nutritional supplements containing antioxidants are advertised for
      better vision health. Do they benefit the average consumer? The literature was
      examined for the effectiveness of antioxidants for human eye health, and for the
      intricacies in collection of such evidence. The following diseases were
      considered: cataract, glaucoma, age-related macular degeneration (AMD),
      retinopathy, retinitis pigmentosa, eye infections, and uveitis. The literature
      indicates that antioxidant supplements plus lutein have a reasonable probability
      of retarding AMD. For glaucoma, such supplements were ineffectual in some studies
      but useful in others. In some studies, antioxidant rich fruits and vegetables
      were also useful for protection against glaucoma. For diabetic retinopathy,
      antioxidant supplements may have a small benefit, if any, but only as an adjunct
      to glycemic control. In very high-risk premature retinopathy and retinitis
      pigmentosa, antioxidant supplements may be beneficial but those with excess
      Vitamin E should be avoided. For cataract, there is no evidence for an advantage
      of such nutritional supplements. However, lubricant drops containing N
      acetylcarnosine may be helpful in initial stages of the disease. For eye
      infections and other causes of uveitis, antioxidants have not been found useful.
      We recommend that a diet high in antioxidant rich foods should be developed as a
      habit from an early age. However, when initial signs of vision health
      deterioration are observed, the appropriate nutritional supplement products may
      be recommended but only to augment the primary medical treatments. 

PMID- 24311112
TI  - Comment on Cassell and Clapperton: A decreasing trend in fall-related hip
      fracture incidence in Victoria, Australia.

PMID- 24311113
TI  - Rapid biochemical response to denosumab in fibrous dysplasia of bone: report of
      two cases.
AB  - We report on the clinical and biochemical outcomes in two adult patients with
      active polyostotic fibrous dysplasia (FD) treated with the RANK-L inhibitor,
      denosumab, following unsatisfactory responses to prior long-term bisphosphonate
      therapy. A 44-year-old female (case 1) who had received a cumulative dose of 20
      mg zoledronic acid over 2.5 years and a 48-year-old male (case 2) who had
      received a cumulative dose of 45 mg zoledronic acid over 8 years both experienced
      minimal reductions in pain scores and markers of bone turnover. Following
      initiation of denosumab 60 mg sc, changes in bone pain, bone turnover [assessed
      by serum amino-terminal propeptide of type I collagen (PINP) and urinary
      deoxypyridinoline] were monitored over a period of 20 and 8 months, respectively.
      Following administration of denosumab, both patients demonstrated a rapid and
      pronounced biochemical response: Within 4-7 weeks, bone turnover markers fell to
      levels within the respective reference range, and one patient reported a
      reduction in pain. Treatment with denosumab was well tolerated. However,
      transient asymptomatic hypocalcaemia and/or hypophosphatemia associated with a
      transient two to threefold increase in serum PTH levels was observed in both
      patients. Dosing intervals for denosumab varied significantly between the two
      patients, depending on disease activity at baseline. Denosumab appears to be
      effective in reducing bone turnover in adult patients with active FD. However,
      caution should be exercised, and patients should be monitored carefully as
      significant fluctuations in biochemical and hormonal indices can occur. 

PMID- 24311116
TI  - Prosthetic reconstruction of complicated auricular defects: use of a hybrid
      prosthetic fabrication technique.

PMID- 24311115
TI  - Physical activity and cancer-specific mortality in the NIH-AARP Diet and Health
      Study cohort.
AB  - Higher physical activity levels have been associated with a lower risk of
      developing various cancers and all-cancer mortality, but the impact of pre
      diagnosis physical activity on cancer-specific death has not been fully
      characterized. In the prospective National Institutes of Health-AARP Diet and
      Health Study with 293,511 men and women, we studied prediagnosis moderate to
      vigorous intensity leisure time physical activity (MVPA) in the past 10 years and
      cancer-specific mortality. Over a median 12.1 years, we observed 15,001 cancer
      deaths. Using Cox proportional hazards regression, we estimated hazard ratios
      (HRs) and 95% confidence intervals (CIs) for MVPA with cancer mortality overall
      and by 20 specific cancer sites, adjusting for relevant risk factors. Compared to
      participants reporting never/rare MVPA, those reporting >7 hr/week MVPA had a
      lower risk of total cancer mortality (HR = 0.89, 95% CI 0.84-0.94; p-trend
      <0.001). When analyzed by cancer site-specific deaths, comparing those reporting
      >7 hr/week of MVPA to those reporting never/rare MVPA, we observed a lower risk
      of death from colon (HR = 0.70; 95% CI 0.57-0.85; p-trend <0.001), liver (0.71;
      0.52-0.98; p-trend = 0.012) and lung cancer (0.84; 0.77-0.92; p-trend <0.001) and
      a significant p-trend for non-Hodgkins lymphoma (0.80; 0.62-1.04; p-trend =
      0.017). An unexpected increased mortality p-trend with increasing MVPA was
      observed for death from kidney cancer (1.42; 0.98-2.03; p-trend = 0.016). Our
      findings suggest that higher prediagnosis leisure time physical activity is
      associated with lower risk of overall cancer mortality and mortality from
      multiple cancer sites. Future studies should confirm observed associations and
      further explore timing of physical activity and underlying biological mechanisms.

PMID- 24311114
TI  - Treatment of skeletal impairment in patients with endogenous hypercortisolism:
      when and how?
AB  - Guidelines for the management of osteoporosis induced by endogenous
      hypercortisolism are not available. Both the American College of Rheumatology and
      the International Osteoporosis Foundation recommend to modulate the treatment of
      exogenous glucocorticoid-induced osteoporosis (GIO) based on the individual
      fracture risk profile (calculated by FRAX) and dose of glucocorticoid used, but
      it is difficult to translate corticosteroid dosages to different degrees of
      endogenous hypercortisolism, and there are no data on validation of FRAX
      stratification method in patients with endogenous hypercortisolism. Consequently,
      it is unclear whether such recommendations may be adapted to patients with
      endogenous hypercortisolism. Moreover, patients with exogenous GIO take
      glucocorticoids since suffering a disease that commonly affects bone. On the
      other hand, the correction of coexistent risk factors, which may contribute to
      increase the fracture risk in patients exposed to glucocorticoid excess, and the
      removal of the cause of endogenous hypercortisolism, may lead to the recovery of
      bone health. Although the correction of hypercortisolism and of possible
      coexistent risk factors is necessary to favor the normalization of bone turnover
      with recovery of bone mass; in some patients, the fracture risk could not be
      normalized and specific anti-osteoporotic drugs should be given. Who, when, and
      how the patient with endogenous hypercortisolism should be treated with bone
      active therapy is discussed. 

PMID- 24311117
TI  - Nuclear anomalies in exfoliated buccal cells in healthy and diabetic individuals
      and the impact of a dietary intervention.
AB  - This study aimed to compare the frequencies of nuclear anomalies in buccal cells
      between diabetic and non-diabetic individuals and to assess the impact of a
      'healthy diet'-a cornerstone in the treatment of diabetes. Seventy-six diabetic
      and 21 non-diabetic individuals participated in this parallel, randomised,
      intervention trial. All participants received information about the importance of
      a healthy diet, while participants randomly assigned to the intervention group
      received additionally 300g of vegetables and 25ml of plant oil rich in
      polyunsaturated fatty acids (PUFA) per day for 8 weeks. Cytogenetic damage in
      buccal cells was assessed at baseline and after 8 weeks using the buccal
      micronucleus cytome assay. Micronucleus (MN) frequency at baseline was
      significantly higher in participants with diabetes (0.58+/-0.300/00) compared
      with non-diabetic individuals (0.28+/-0.290/00). Further analysis of baseline
      data revealed significantly higher MN levels in participants of the highest
      tertile of waist circumference (+40%), fasting plasma glucose (+55%), glycated
      haemoglobin (+41%) and cardiovascular disease risk (+39%) relative to
      participants of the lowest tertile. The dietary intervention had no effect on MN
      frequencies. Glycated haemoglobin and biomarkers reflecting cytokinetic defect or
      acute cell death were reduced in both the intervention and 'information only'
      groups. The results of this study suggest a strong impact of abdominal obesity
      and glucose metabolism on genomic stability. Similar effects on nuclear anomalies
      were observed in the 'information only' group and the intervention group
      receiving vegetables and PUFA-rich plant oil. 

PMID- 24311118
TI  - Smokers run increased risk of developing anti-natalizumab antibodies.
AB  - BACKGROUND: Smoking may contribute to the induction of neutralizing antibodies to
      interferon beta-1a. OBJECTIVE: In this study, we aimed to investigate the
      influence of smoking on the risk of developing antibodies to natalizumab, another
      biological drug in the treatment of multiple sclerosis. METHODS: This report is
      based on 1338 natalizumab-treated multiple sclerosis patients included in either
      of two Swedish case-control studies in which information on smoking habits was
      collected. Using logistic regression, patients with different smoking habits were
      compared regarding risk of developing anti-natalizumab antibodies, by calculating
      odds ratios with 95% confidence intervals. RESULTS: Compared with nonsmokers, the
      odds ratio of developing anti-natalizumab antibodies was 2.4 (95% CI 1.2-4.4) for
      patients who smoked at the time of screening, and a significant trend showed
      higher risk of developing antibodies with higher intensity of smoking. When
      smoking within two years prior to screening was considered, the odds ratio of
      developing anti-natalizumab antibodies was 2.7 (1.5-5.1). INTERPRETATIONS: The
      finding strengthens our hypothesis of the lungs as immune-reactive organs on
      irritation in relation to autoimmune responses, and may also be of clinical
      relevance since antibodies against natalizumab abrogate the therapeutic effect of
      the treatment.

PMID- 24311120
TI  - Environmental noise pollution in the United States: developing an effective
      public health response.
AB  - BACKGROUND: Tens of millions of Americans suffer from a range of adverse health
      outcomes due to noise exposure, including heart disease and hearing loss.
      Reducing environmental noise pollution is achievable and consistent with national
      prevention goals, yet there is no national plan to reduce environmental noise
      pollution. OBJECTIVES: We aimed to describe some of the most serious health
      effects associated with noise, summarize exposures from several highly prevalent
      noise sources based on published estimates as well as extrapolations made using
      these estimates, and lay out proven mechanisms and strategies to reduce noise by
      incorporating scientific insight and technological innovations into existing
      public health infrastructure. DISCUSSION: We estimated that 104 million
      individuals had annual LEQ(24) levels > 70 dBA (equivalent to a continuous
      average exposure level of >70 dBA over 24 hr) in 2013 and were at risk of noise
      induced hearing loss. Tens of millions more may be at risk of heart disease, and
      other noise-related health effects. Direct regulation, altering the informational
      environment, and altering the built environment are the least costly, most
      logistically feasible, and most effective noise reduction interventions.
      CONCLUSION: Significant public health benefit can be achieved by integrating
      interventions that reduce environmental noise levels and exposures into the
      federal public health agenda.

PMID- 24311121
TI  - High sensitivity molecule detection by plasmonic nanoantennas with selective
      binding at electromagnetic hotspots.
AB  - We report a highly sensitive biomolecule detection by plasmonic nanoantenna
      arrays with selective binding at the optical hotspots. The plasmonic nanoantennas
      consist of two separated Au nanorods with a thin Ti disk placed in between. By
      using selective surface modification chemistry, controlled binding occurs only in
      the gaps between the plasmonic nanoantennas, which ensures a high detection
      sensitivity. Both optical characterization using a dark field microscope and the
      FDTD simulation show that after the streptavidin binding, the signal increases
      with decreasing gap size. Compared to a single nanorod, the signal obtained per
      bound molecule in the nanoantennas increases by a factor of six, which is
      promising with respect to the future detection of single molecules. 

PMID- 24311122
TI  - Preface.

PMID- 24311119
TI  - Metastasis suppressors in breast cancers: mechanistic insights and clinical
      potential.
AB  - For the most part, normal epithelial cells do not disseminate to other parts of
      the body and proliferate, as do metastatic cells. Presumably, a class of
      molecules-termed metastasis suppressors-are involved in this homeostatic control.
      Metastasis suppressors are, by definition, cellular factors that, when re
      expressed in metastatic cells, functionally inhibit metastasis without
      significantly inhibiting tumor growth. In this brief review, we catalog known
      metastasis suppressors, what is known about their mechanism(s) of action, and
      experimental and clinical associations to date. 

PMID- 24311123
TI  - Carbon biogeochemistry and climate change.
AB  - The rapid increase of atmospheric CO2 resulting from anthropogenic activites has
      stimulated a great deal of interest in the carbon cycle. Important decisions need
      to be made about future tolerable levels of atmospheric CO2 content, as well as
      the land and fossil fuel use strategies that will permit us to achieve these
      goals. The vast amount of new data on atmospheric CO2 content and ancillary
      properties that has become available during the last decade, and the development
      of models to interpret these data, have led to significant advances in our
      capacity to deal with such issues. However, a major continuing source of
      uncertainty is the role of photosynthesis in providing a sink for anthropogenic
      emissions. It is thus appropriate that a new evaluation of the status of our
      understanding of this issue should be made at this time.The aim of this paper is
      to provide a setting for the papers that follow by giving an overview of the role
      of carbon dioxide in climate, the biogeochemical processes that control its
      distribution, and the evolution of carbon dioxide through time from the origin of
      the earth to the present. We begin with a discussion of relevant processes. We
      then proceed to a more detailed discussion of the time periods that are best
      documented: the late Pleistocene (during which time large continental ice sheets
      waxed and waned) and the modern era of anthropogenic impact on the carbon cycle. 

PMID- 24311124
TI  - The role of phytoplankton photosynthesis in global biogeochemical cycles.
AB  - Phytoplankton biomass in the world's oceans amounts to only ?1-2% of the total
      global plant carbon, yet these organisms fix between 30 and 50 billion metric
      tons of carbon annually, which is about 40% of the total. On geological time
      scales there is profound evidence of the importance of phytoplankton
      photosynthesis in biogeochemical cycles. It is generally assumed that present
      phytoplankton productivity is in a quasi steady-state (on the time scale of
      decades). However, in a global context, the stability of oceanic photosynthetic
      processes is dependent on the physical circulation of the upper ocean and is
      therefore strongly influenced by the atmosphere. The net flux of atmospheric
      radiation is critical to determining the depth of the upper mixed layer and the
      vertical fluxes of nutrients. These latter two parameters are keys to determining
      the intensity, and spatial and temporal distributions of phytoplankton blooms.
      Atmospheric radiation budgets are not in steady-state. Driven largely by
      anthropogenic activities in the 20th century, increased levels of IR- absorbing
      gases such as CO2, CH4 and CFC's and NOx will potentially increase atmospheric
      temperatures on a global scale. The atmospheric radiation budget can affect
      phytoplankton photosynthesis directly and indirectly. Increased temperature
      differences between the continents and oceans have been implicated in higher wind
      stresses at the ocean margins. Increased wind speeds can lead to higher nutrient
      fluxes. Throughout most of the central oceans, nitrate concentrations are sub
      micromolar and there is strong evidence that the quantum efficiency of
      Photosystem II is impaired by nutrient stress. Higher nutrient fluxes would lead
      to both an increase in phytoplankton biomass and higher biomass-specific rates of
      carbon fixation. However, in the center of the ocean gyres, increased radiative
      heating could reduce the vertical flux of nutrients to the euphotic zone, and
      hence lead to a reduction in phytoplankton carbon fixation. Increased
      desertification in terrestrial ecosystems can lead to increased aeolean loadings
      of essential micronutrients, such as iron. An increased flux of aeolean
      micronutrients could fertilize nutrient-replete areas of the open ocean with
      limiting trace elements, thereby stimulating photosynthetic rates. The factors
      which limit phytoplankton biomass and photosynthesis are discussed and examined
      with regard to potential changes in the Earth climate system which can lead the
      oceans away from steady-state. While it is difficult to confidently deduce
      changes in either phytoplankton biomass or photosynthetic rates on decadal time
      scales, time-series analysis of ocean transparency data suggest long-term trends
      have occurred in the North Pacific Ocean in the 20th century. However,
      calculations of net carbon uptake by the oceans resulting from phytoplankton
      photosynthesis suggest that without a supply of nutrients external to the ocean,
      carbon fixation in the open ocean is not presently a significant sink for excess
      atmospheric CO2. 

PMID- 24311125
TI  - Carbon fixation and carbon availability in marine phytoplankton.
AB  - It is widely believed that inorganic C does not limit the rate of short-term
      photosynthesis, the net productivity, or the maximum biomass, of marine
      phytoplankton. This lack of inorganic C restriction is less widely believed to
      hold for phytoplankton in many low alkalinity freshwaters or for seaweed in
      nutrient-enriched rock pools. These views are examined in the context of the
      physical chemistry of the inorganic C system in natural waters and of the ways in
      which various taxa of phytoplankton deal with inorganic C and discriminate
      between (12)C and (13)C. Using this information to interpret data obtained in the
      ocean or in freshwater suggests that short-term photosynthesis, production rate,
      and achieved biomass, of phytoplankton are rarely limited by inorganic C supply
      but, rather, that the widely suggested factors of limited light, nitrogen or
      phosphorus supply are the resource inputs which restrict productivity. Global
      change, by increasing atmospheric CO2 partial pressure and global mean
      temperatures, is likely to increase the mean CO2 concentration in the atmosphere,
      but the corresponding change in the oceans will be much less. There are, however,
      genotypic differences in the handling of inorganic C among the diversity of
      marine phytoplankton, and in impact on use of limiting nutrients, so increases in
      the mean CO2 and HCO3 (-) concentrations in surface ocean waters could cause
      changes in species composition. However, the rarity of inorganic C limitation of
      marine phytoplankton short-term photosynthesis, net productivity, or the maximum
      biomass, in today's ocean means that global change is unlikely to increase these
      three values in the ocean. 

PMID- 24311126
TI  - The role of iron in phytoplankton photosynthesis, and the potential for iron
      limitation of primary productivity in the sea.
AB  - Iron supply has been suggested to influence phytoplankton biomass, growth rate
      and species composition, as well as primary productivity in both high and low NO3
      (-) surface waters. Recent investigations in the equatorial Pacific suggest that
      no single factor regulates primary productivity. Rather, an interplay of bottom
      up (i.e., ecophysiological) and top-down (i.e., ecological) factors appear to
      control species composition and growth rates. One goal of biological oceanography
      is to isolate the effects of single factors from this multiplicity of
      interactions, and to identify the factors with a disproportionate impact.
      Unfortunately, our tools, with several notable exceptions, have been largely
      inadequate to the task. In particular, the standard technique of nutrient
      addition bioassays cannot be undertaken without introducing artifacts. These so
      called 'bottle effects' include reducing turbulence, isolating the enclosed
      sample from nutrient resupply and grazing, trapping the isolated sample at a
      fixed position within the water column and thus removing it from vertical
      movement through a light gradient, and exposing the sample to potentially
      stimulatory or inhibitory substances on the enclosure walls. The problem faced by
      all users of enrichment experiments is to separate the effects of controlled
      nutrient additions from uncontrolled changes in other environmental and
      ecological factors. To overcome these limitations, oceanographers have sought
      physiological or molecular indices to diagnose nutrient limitation in natural
      samples. These indices are often based on reductions in the abundance of
      photosynthetic and other catalysts, or on changes in the efficiency of these
      catalysts. Reductions in photosynthetic efficiency often accompany nutrient
      limitation either because of accumulation of damage, or impairment of the ability
      to synthesize fully functional macromolecular assemblages. Many catalysts
      involved in electron transfer and reductive biosyntheses contain iron, and the
      abundances of most of these catalysts decline under iron-limited conditions.
      Reductions of ferredoxin or cytochrome f content, nitrate assimilation rates, and
      dinitrogen fixation rates are amongst the diagnostics that have been used to
      infer iron limitation in some marine systems. An alternative approach to
      diagnosing iron-limitation uses molecules whose abundance increases in response
      to iron-limitation. These include cell surface iron-transport proteins, and the
      electron transfer protein flavodoxin which replaces the Fe-S protein ferredoxin
      in many Fe-deficient algae and cyanobacteria. 

PMID- 24311127
TI  - Ultraviolet radiation, ozone depletion, and marine photosynthesis.
AB  - Concerns about stratospheric ozone depletion have stimulated interest in the
      effects of UVB radiation (280-320 nm) on marine phytoplankton. Research has shown
      that phytoplankton photosynthesis can be severely inhibited by surface irradiance
      and that much of the effect is due to UV radiation. Quantitative generalization
      of these results requires a biological weighting function (BWF) to quantify UV
      exposure appropriately. Different methods have been employed to infer the general
      shape of the BWF for photoinhibition in natural phytoplankton, and recently,
      detailed BWFs have been determined for phytoplankton cultures and natural
      samples. Results show that although UVB photons are more damaging than UVA (320
      400 nm), the greater fluxes of UVA in the ocean cause more UV inhibition. Models
      can be used to analyze the sensitivity of water column productivity to UVB and
      ozone depletion. Assumptions about linearity and time-dependence strongly
      influence the extrapolation of results. Laboratory measurements suggest that UV
      inhibition can reach a steady-state consistent with a balance between damage and
      recovery processes, leading to a non-linear relationship between weighted fluence
      rate and inhibition. More testing for natural phytoplankton is required, however.
      The relationship between photoinhibition of photosynthesis and decreases in
      growth rate is poorly understood, so long-term effects of ozone depletion are
      hard to predict. However, the wide variety of sensitivities between species
      suggests that some changes in species composition are likely. Predicted effects
      of ozone depletion on marine photosynthesis cannot be equated to changes in
      carbon flux between the atmosphere and ocean. Nonetheless, properly designed
      studies on the effects of UVB can help identify which physiological and
      ecological processes are most likely to dominate the responses of marine
      ecosystems to ozone depletion. 

PMID- 24311128
TI  - Scaling CO2-photosynthesis relationships from the leaf to the canopy.
AB  - Responses of individual leaves to short-term changes in CO2 partial pressure have
      been relatively well studied. Whole-plant and plant community responses to
      elevated CO2 are less well understood and scaling up from leaves to canopies will
      be complicated if feedbacks at the small scale differ from feedbacks at the large
      scale. Mathematical models of leaf, canopy, and ecosystem processes are important
      tools in the study of effects on plants and ecosystems of global environmental
      change, and in particular increasing atmospheric CO2, and might be used to scale
      from leaves to canopies. Models are also important in assessing effects of the
      biosphere on the atmosphere. Presently, multilayer and big leaf models of canopy
      photosynthesis and energy exchange exist. Big leaf models - which are advocated
      here as being applicable to the evaluation of impacts of 'global change' on the
      biosphere - simplify much of the underlying leaf-level physics, physiology, and
      biochemistry, yet can retain the important features of plant-environment
      interactions with respect to leaf CO2 exchange processes and are able to make
      useful, quantitative predictions of canopy and community responses to
      environmental change. The basis of some big leaf models of photosynthesis,
      including a new model described herein, is that photosynthetic capacity and
      activity are scaled vertically within a canopy (by plants themselves) to match
      approximately the vertical profile of PPFD. The new big leaf model combines
      physically based models of leaf and canopy level transport processes with a
      biochemically based model of CO2 assimilation. Predictions made by the model are
      consistent with canopy CO2 exchange measurements, although a need exists for
      further testing of this and other canopy physiology models with independent
      measurements of canopy mass and energy exchange at the time scale of 1 h or less.

PMID- 24311129
TI  - Acclimation of photosynthesis to increasing atmospheric CO2: The gas exchange
      perspective.
AB  - The nature of photosynthetic acclimation to elevated CO2 is evaluated from the
      results of over 40 studies focusing on the effect of long-term CO2 enrichment on
      the short-term response of photosynthesis to intercellular CO2 (the A/Ci
      response). The effect of CO2 enrichment on the A/Ci response was dependent on
      growth conditions, with plants grown in small pots (< 5 L) or low nutrients
      usually exhibiting a reduction of A at a given Ci, while plants grown without
      nutrient deficiency in large pots or in the field tended to exhibit either little
      reduction or an enhancement of A at a given Ci following a doubling or tripling
      of atmospheric CO2 during growth. Using theoretical interpretations of A/Ci
      curves to assess acclimation, it was found that when pot size or nutrient
      deficiency was not a factor, changes in the shape of A/Ci curves which are
      indicative of a reallocation of resources within the photosynthetic apparatus
      typically were not observed. Long-term CO2 enrichment usually had little effect
      or increased the value of A at all Ci. However, a minority of species grown at
      elevated CO2 exhibited gas exchange responses indicative of a reduced amount of
      Rubisco and an enhanced capacity to metabolize photosynthetic products. This type
      of response was considered beneficial because it enhanced both photosynthetic
      capacity at high CO2 and reduced resource investment in excessive Rubisco
      capacity. The ratio of intercellular to ambient CO2 (the Ci/Ca ratio) was used to
      evaluate stomatal acclimation. Except under water and humidity stress, Ci/Ca
      exhibited no consistent change in a variety of C3 species, indicating no stomatal
      acclimation. Under drought or humidity stress, Ci/Ca declined in high-CO2 grown
      plants, indicating stomata will become more conservative during stress episodes
      in future high CO2 environments. 

PMID- 24311130
TI  - Photosynthetic acclimation in trees to rising atmospheric CO2: A broader
      perspective.
AB  - Analysis of leaf-level photosynthetic responses of 39 tree species grown in
      elevated concentrations of atmospheric CO2 indicated an average photosynthetic
      enhancement of 44% when measured at the growth [CO2]. When photosynthesis was
      measured at a common ambient [CO2], photosynthesis of plants grown at elevated
      [CO2] was reduced, on average, 21% relative to ambient-grown trees, but
      variability was high. The evidence linking photosynthetic acclimation in trees
      with changes at the biochemical level is examined, along with anatomical and
      morphological changes in trees that impact leaf- and canopy-level photosynthetic
      response to CO2 enrichment. Nutrient limitations and variations in sink strength
      appear to influence photosynthetic acclimation, but the evidence in trees for one
      predominant factor controlling acclimation is lacking. Regardless of the
      mechanisms that underlie photosynthetic acclimation, it is doubtful that this
      response will be complete. A new focus on adjustments to rising [CO2] at canopy,
      stand, and forest scales is needed to predict ecosystem response to a changing
      environment. 

PMID- 24311131
TI  - Effects of nitrogen supply on the acclimation of photosynthesis to elevated CO2.
AB  - A common observation in plants grown in elevated CO2 concentration is that the
      rate of photosynthesis is lower than expected from the dependence of
      photosynthesis upon CO2 concentration in single leaves of plants grown at present
      CO2 concentration. Furthermore, it has been suggested that this apparent down
      regulation of photosynthesis may be larger in leaves of plants at low nitrogen
      supply than at higher nitrogen supply. However, the available data are rather
      limited and contradictory. In this paper, particular attention is drawn to the
      way in which whole plant growth response to N supply constitutes a variable sink
      strength for carbohydrate usage and how this may affect photosynthesis. The need
      for further studies of the acclimation of photosynthesis at elevated CO2 in
      leaves of plants whose N supply has resulted in well-defined growth rate and sink
      activity is emphasised, and brief consideration is made of how this might be
      achieved. 

PMID- 24311132
TI  - Optimal acclimation of the C3 photosynthetic system under enhanced CO2.
AB  - A range of studies of C3 plants have shown that there is a change in both the
      carbon flux and the pattern of nitrogen allocation when plants are grown under
      enhanced CO2. This paper examines evidence that allocation of nitrogen both to
      and within the photosynthetic system is optimised with respect to the carbon
      flux. A model is developed which predicts the optimal relative allocation of
      nitrogen to key enzymes of the photosynthetic system as a function of CO2
      concentration. It is shown that evidence from flux control analysis is broadly
      consistent with this model, although at high nitrogen and under certain
      conditions at low nitrogen experimental data are not consistent with the model.
      Acclimation to enhanced CO2 is also assessed in terms of resource allocation
      between photosynthate sources and sinks. A means of assessing the optimisation of
      this source-sink allocation is proposed, and several studies are examined within
      this framework. It is concluded that C3 plants probably possess the genetic
      feedback mechanisms required to efficiently 'smooth out" any imbalance within the
      photosynthetic system caused by a rise in atmospheric CO2. 

PMID- 24311133
TI  - Acclimation of photosynthetic proteins to rising atmospheric CO2.
AB  - In this review we discuss how the photosynthetic apparatus, particularly Rubisco,
      acclimates to rising atmospheric CO2 concentrations (ca). Elevated ca alters the
      control exerted by different enzymes of the Calvin cycle on the overall rate of
      photosynthetic CO2 assimilation, so altering the requirement for different
      functional proteins. A decreased flux of carbon through the photorespiratory
      pathway will decrease requirements for these enzymes. From modeling of the
      response of CO2 uptake (A) to intracellular CO2 concentration (ci) it is shown
      that the requirement for Rubisco is decreased at elevated ca, whilst that for
      proteins limiting ribulose 1,5 bisphosphate regeneration may be increased. This
      balance may be altered by other interactions, in particular plasticity of sinks
      for photoassimilate and nitrogen supply; hypotheses on these interactions are
      presented. It is speculated that increased accumulation of carbohydrate in leaves
      developed at elevated ca may signal the 'down regulation' of Rubisco. The
      molecular basis of this 'down regulation' is discussed in terms of the repression
      of photosynthetic gene expression by the elevated carbohydrate concentrations.
      This molecular model is then used to predict patterns of acclimation of
      perennials to long term growth in elevated ca. 

PMID- 24311135
TI  - Possible mechanisms for the inhibition of photosynthesis by ozone.
AB  - Tropospheric ozone produced by industrial civilization is widespread. Although
      the levels are not clearly life threatening, they do have the potential to
      inhibit normal plant productivity, thought to be by an inhibition of
      photosynthesis. While the mechanism for this inhibition is not yet clear, there
      are several hypotheses for its cause. It is unlikely that ozone can penetrate the
      cell membrane unreacted; therefore, reactions at the plasma membrane either
      causing general ionic and metabolic disturbance within the cell or causing the
      production of unidentified toxic products must ultimately produce the alterations
      within the chloroplasts. While model systems, such as individual biochemicals,
      isolated chloroplasts, and algae, can give some understanding of possible
      reactions, they cannot provide the full story. One continuing controversy
      revolves about the role of stomata in the inhibition process-they play an
      important role, but the full interaction between stomatal closure and inhibition
      of photosynthesis has not yet emerged. In order to reach a political compromise
      on air quality standards, we need to have a good understanding of the fundamental
      mechanisms by which ozone causes any decline in plant productivity. 

PMID- 24311134
TI  - Feedback control of gene expression.
AB  - Although feedback regulation of photosynthesis by carbon metabolites has long
      been recognized and investigated, its underlying molecular mechanisms remain
      unclear. The recent discovery that glucose and acetate trigger global repression
      of maize photosynthetic gene transcription provides the first direct evidence
      that a fundamental mechanism is used for feedback regulation of photosynthesis in
      higher plants. The metabolic repression of photosynthetic genes has now been
      found in many higher plants and is likely universal. It overrides other
      regulation by light, tissue type and developmental stage, and serves potentially
      as the molecular basis of interactions between sink and source tissues. Using
      simplified and convenient cellular systems and transgenic plants, the study of
      metabolic regulation of gene expression offers an excellent opportunity for the
      understanding of global and coordinate gene control and metabolite-mediated
      signal transduction in higher plants. 

PMID- 24311136
TI  - Biochemical and molecular basis for impairment of photosynthetic potential.
AB  - Ozone induces reductions in net photosynthesis in a large number of plant
      species. A primary mechanism by which photosynthesis is reduced is through impact
      on carbon dioxide fixation. Ozone induces loss in Rubisco activity associated
      with loss in concentration of the protein. Evidence is presented that ozone may
      induce oxidative modification of Rubisco leading to subsequent proteolysis. In
      addition, plants exposed to ozone sustain reduction in rbcS, the mRNA for the
      small subunit of Rubisco. This loss in rbcS mRNA may lead to a reduced potential
      for synthesis of the protein. The regulation of O3-induced loss of Rubisco, and
      implications of the decline in this protein in relation to accelerated senescence
      are discussed. 

PMID- 24311137
TI  - Effects of UV-B radiation on photosynthesis and growth of terrestrial plants.
AB  - The photosynthetic apparatus of some plant species appears to be well-protected
      from direct damage from UV-B radiation. Leaf optical properties of these species
      apparently minimizes exposure of sensitive targets to UV-B radiation. However,
      damage by UV-B radiation to Photosystem II and Rubisco has also been reported.
      Secondary effects of this damage may include reductions in photosynthetic
      capacity, RuBP regeneration and quantum yield. Furthermore, UV-B radiation may
      decrease the penetration of PAR, reduce photosynthetic and accessory pigments,
      impair stomatal function and alter canopy morphology, and thus indirectly retard
      photosynthetic carbon assimilation. Subsequently, UV-B radiation may limit
      productivity in many plant species. In addition to variability in sensitivity to
      UV-B radiation, the effects of UV-B radiation are further confounded by other
      environmental factors such as CO2, temperature, light and water or nutrient
      availability. Therefore, we need a better understanding of the mechanisms of
      tolerance to UV-B radiation and of the interaction between UV-B and other
      environmental factors in order to adequately assess the probable consequences of
      a change in solar radiation. 

PMID- 24311139
TI  - The foolishness of preaching.

PMID- 24311140
TI  - The church's response to the severely emotionally distressed.
AB  - The clergy and church are deeply involved in aiding persons who have emotional
      problems. Many of those seeking help manifest psychotic symptoms. This paper
      addresses the issue of how organized religion can better understand and minister
      to the needs of those suffering severe emotional distress. Programs and models at
      national and local levels are discussed, with an emphasis upon the latter. Local
      level models include mental health promoting aspects of local church functions,
      pastoral counseling programs of the local church, the Wholistic Health Center
      (WHC), Community Organization for Personal Enrichment (COPE), Christian Action
      Ministry (CAM), and Mennonite Mental Health Services. Clinical vignettes
      illustrate the functioning of these models. 

PMID- 24311138
TI  - UV-B damage and protection at the molecular level in plants.
AB  - Influx of solar UV-B radiation (280-320 nm) will probably increase in the future
      due to depletion of stratospheric ozone. In plants, there are several targets for
      the deleterious UV-B radiation, especially the chloroplast. This review
      summarizes the early effects and responses of low doses of UV-B at the molecular
      level. The DNA molecules of the plant cells are damaged by UV due to the
      formation of different photoproducts, such as pyrimidine dimers, which in turn
      can be combatted by specialized photoreactivating enzyme systems. In the
      chloroplast, the integrity of the thylakoid membrane seems to be much more
      sensitive than the activities of the photosynthetic components bound within.
      However, the decrease of mRNA transcripts for the photosynthetic complexes and
      other chloroplast proteins are among very early events of UV-B damage, as well as
      protein synthesis. Other genes, encoding defence-related enzymes, e.g., of the
      flavonoid biosynthetic pathway, are rapidly up-regulated after commencement of UV
      B exposure. Some of the cis-acting nucleotide elements and trans-acting protein
      factors needed to regulate the UV-induced expression of the parsley chalcone
      synthase gene are known. 

PMID- 24311141
TI  - Disease as a value statement.
AB  - In an attempt to examine the unconscious roots of values, this paper explores
      Gotthard Booth's psychosomatic theory that disease is a message of the whole
      person. It outlines his work in describing distinctive personality types who
      characteristically become ill through the disease of the organ system that is
      dominant for their life-style. The disease represents accommodation in the
      person's object relatedness and as such reflects the operation of unconscious
      values and indicates possibilities for therapy. Because the cultural environment
      helps condition the dominant organ response, Booth's work also has relevance for
      developing a sociology of value and suggests a prophylactic role for religion. 

PMID- 24311142
TI  - Suffering and wisdom.
AB  - Suffering is frequent in life, often ensuing when a wished-for state cannot be
      realized. One common response to suffering is mourning. Mourning may take
      problematic forms, and this can lead to chronic denial or embitterment or despair
      or stagnation. On the other hand, mourning may occur in such manner as to
      facilitate meaning in life, empathy, caring, and perspective. One's "myths" and
      beliefs often affect the mourning process and may themselves be influenced by
      that process. Different myths accompany or influence different identity patterns
      and life-styles. The core concepts of religion are often associated with certain
      myths and beliefs that may inspire meaning and courage, caring and wisdom. 

PMID- 24311143
TI  - Natural science and the healing of persons.
AB  - The importance of a counselor's philosophical point of departure is emphasized.
      Viewing the self as "a conscious, free, and responsible decision-making actor in
      a world of substantial and self-transcendent meanings and purposes" is suggested
      as the core of a definition that uses an existentialist point of departure. In
      the light of this definition, four specific inadequacies of counseling that uses
      a natural-scientific point of departure are identified and discussed: 1) it is
      overreductionistic; 2) it reinforces the view of self as "helpless victim"; 3) it
      disregards the importance of transpersonal concerns; 4) it ignores the importance
      of conflicting world views between therapist and client. 

PMID- 24311144
TI  - Some concerns of bereaved parents.
AB  - This article grows out of a pediatrics chaplain's three years of experience
      conducting a support group for bereaved parents. After a brief description of the
      formation of the group, the article identifies the common grief concerns that
      bereaved parents regularly express when they come together. 

PMID- 24311145
TI  - The church's ministry to singles: A family model.
AB  - The authors provide a theoretical introduction for the church's ministry to
      singles by reviewing the family therapy literature as it pertains to familial
      disengagement or enmeshment and interpersonal mutuality or isolation.
      Belongingness based on consanguinity must eventually be replaced by belongingness
      rooted in consensuality or commitment. The single person must seek such
      commitment outside the institution of marriage. The church can offer
      belongingness through establishing parity, de-emphasizing segregation, promoting
      inclusion, and practicing community. 

PMID- 24311146
TI  - A biblical and historical study of homosexuality.
AB  - This study is a synthesis of biblical and historical material regarding the place
      of homosexuality in the Christian churches. The author argues that all sexual
      activity, both heterosexual and homosexual in orientation, should be judged
      appropriate for Christians when it is a responsible, mutually respectful and
      loving act between adult persons that is intended to enhance the building and
      maintaining of whole persons. Therefore, if a person is in all other ways
      qualified for membership and its contingent responsibilities in the Christian
      community (or any other community), his or her sexual orientation and behavior
      should not be a barrier. 

PMID- 24311147
TI  - Platinum-based phosphorescent double-decker tweezers: a strategy for extended
      heterologous metal-metal interactions.

PMID- 24311150
TI  - Rete testis adenomatous hyperplasia: our experience.
AB  - The word "adenomatous hyperplasia of rete testis" (AHRT) was used by M. Nistal et
      Al. for the first time in an article about the cystic dysplasia of the testis
      (1976). AHRT is a benign lesion of the testis. The patient who came to our
      attention was studied with a testicular echo color Doppler that identified a
      solid, well circumscribed and hypoechoic mass of 4.5 x3.8mm as diameter,
      localized in the upper third of the right testicle and with a perilesional
      vascularization pattern. The preoperative study was based on an accurate medical
      history, on an ultrasound with contrast and on a RMI. The treatment consisted in
      an echo guided excisional biopsy of the testicular lesion, considering this as
      the best approach for those testicular neoformation difficult to define, with a
      lot of benefits for the patients, especially for those monorchid.

PMID- 24311149
TI  - Chimeric antigen receptors for the adoptive T cell therapy of hematologic
      malignancies.
AB  - The genetic modification of autologous T cells with chimeric antigen receptors
      (CARs) represents a breakthrough for gene engineering as a cancer therapy for
      hematologic malignancies. By targeting the CD19 antigen, we have demonstrated
      robust and rapid anti-leukemia activity in patients with heavily pre-treated and
      chemotherapy-refractory B cell acute lymphoblastic leukemia (B-ALL). We
      demonstrated rapid induction of deep molecular remissions in adults, which has
      been recently confirmed in a case report involving a child with B-ALL. In
      contrast to the results when treating B-ALL, outcomes have been more modest in
      patients with chronic lymphocytic leukemia (CLL) or other non-hodgkin's lymphoma
      (NHL). We review the clinical trial experience targeting B-ALL and CLL and
      speculate on the possible reasons for the different outcomes and propose
      potential optimization to CAR T cell therapy when targeting CLL or other indolent
      NHL. Lastly, we discuss the pre-clinical development and potential for clinical
      translation for using CAR T cells against multiple myeloma and acute myeloid
      leukemia. We highlight the potential risks and benefits by targeting these poor
      outcome hematologic malignancies. 

PMID- 24311151
TI  - In vitro activity of favipiravir and neuraminidase inhibitor combinations against
      oseltamivir-sensitive and oseltamivir-resistant pandemic influenza A (H1N1)
      virus.
AB  - Few anti-influenza drugs are licensed in the United States for the prevention and
      therapy of influenza A and B virus infections. This shortage, coupled with
      continuously emerging drug resistance, as detected through a global surveillance
      network, seriously limits our anti-influenza armamentarium. Combination therapy
      appears to offer several advantages over traditional monotherapy in not only
      delaying development of resistance but also potentially enhancing single
      antiviral activity. In the present study, we evaluated the antiviral drug
      susceptibilities of fourteen pandemic influenza A (H1N1) virus isolates in MDCK
      cells. In addition, we evaluated favipiravir (T-705), an investigational drug
      with a broad antiviral spectrum and a unique mode of action, alone and in dual
      combination with the neuraminidase inhibitors (NAIs) oseltamivir, peramivir, or
      zanamivir, against oseltamivir-sensitive pandemic influenza A/California/07/2009
      (H1N1) and oseltamivir-resistant A/Hong Kong/2369/2009 (H1N1) virus. Mean
      inhibitory values showed that the tested virus isolates remained sensitive to
      commonly used antiviral drugs, with the exception of the Hong Kong virus isolate.
      Drug dose-response curves confirmed complete drug resistance to oseltamivir,
      partial sensitivity to peramivir, and retained susceptibility to zanamivir and
      favipiravir against the A/Hong Kong/2369/2009 virus. Three-dimensional analysis
      of drug interactions using the MacSynergy(TM) II program indicated an overall
      synergistic interaction when favipiravir was combined with the NAIs against the
      oseltamivir-sensitive influenza virus, and an additive effect against the
      oseltamivir-resistant virus. Although the clinical relevance of these drug
      combinations remains to be evaluated, results obtained from this study support
      the use of combination therapy with favipiravir and NAIs for treatment of human
      influenza virus infections.

PMID- 24311148
TI  - TB and HIV in the Central African region: current knowledge and knowledge gaps.
AB  - PURPOSE: Reliable and comprehensive data on the HIV/AIDS and TB co-pandemics from
      Central Africa remain scarce. This systematic review provides a comprehensive
      overview on current and past research activities in the region and provides a
      basis for future research work to close knowledge gaps. METHODS: The scientific
      literature was searched for publications meeting the following search terms:
      "tuberculosis" or "HIV" or "acquired immunodeficiency syndrome", combined with
      "Central Africa", or the names of individual countries within the region.
      Original studies, reviews and case series were included, and a selection of
      relevant articles was made. RESULTS: Most research in the field of HIV and TB has
      been conducted in Cameroon, where the epidemics have been described fairly well.
      The Democratic Republic of Congo ranked second on the amount of publications,
      despite the civil wars over the past several decades. Very little has been
      published on HIV and TB in the other countries, possibly due to the poor
      infrastructure of health care systems, lack of scientific capacity building or
      shortage of laboratory equipment. CONCLUSIONS: Despite the relatively high burden
      of HIV and TB in the Central African region, the amount of research activities on
      these topics is limited. A better understanding of the co-epidemics in this
      region is urgently needed. The occurrence of opportunistic infections, treatment
      complications and drug resistance in TB and HIV need to be better described; the
      failure of public health systems needs to be understood, and research
      infrastructure needs to be developed. Only then will it be possible to turn the
      tide against the HIV and TB epidemics in this region.

PMID- 24311152
TI  - Anti-hepatitis B activity of isoquinoline alkaloids of plant origin.
AB  - Hepatitis B virus (HBV) is the causative agent of B-type hepatitis in humans, a
      vaccine-preventable disease. Despite the availability of effective vaccines,
      globally, 2 billion people show evidence of past or current HBV infection, of
      which 350 million people are persistently infected, with an estimated annual
      increase of 1 million. There is no cure for chronic HBV infections, which are
      associated with cirrhotic liver failure and with an increased risk of developing
      hepatocellular carcinoma. Hepatitis antiviral research has focused primarily on
      the development of inhibitors of viral polymerase through the use of nucleoside
      analogues. Therefore, there is an urgent need for the development of non
      nucleoside compounds to be used as an alternative or to complement the current
      therapy. To address this need, 18 isoquinoline alkaloids were evaluated for their
      potential antiviral activity against HBV in vitro. 

PMID- 24311153
TI  - Highly curved bowl-shaped fragments of fullerenes: synthesis, structural
      analysis, and physical properties.
AB  - Highly curved buckybowls 3, 4, and 5 were synthesized from planar precursors,
      fluoranthenes 8, benzo[k]fluoranthenes 10 and naphtho[1,2-k]
      cyclopenta[cd]fluoranthenes 12, respectively, using straightforward palladium
      catalyzed cyclization reactions. These fluoranthene-based starting materials were
      easily prepared from 1,8-bis(arylethynyl)naphthalenes 6. Both buckybowls 3 and 4
      are fragments of C60 , whereas 5 is a unique subunit of C70 . The curved
      structures were identified by X-ray crystallography, and they are deep bowls. The
      maximum pi-orbital axis vector (POAV) pyramidalization angle in both 3 and 4 is
      12.8 degrees . Such a high curvature is very rarely obtained. Buckybowls 5 are
      less curved than the others because they have a lower density of five-membered
      rings, analogous to the tube portion of C70 . Cyclopentaannulation increases the
      bowl depths of 3 and 4, but not the maximum POAV pyramidalization angle. Among
      the eight buckybowls studied herein, five form polar crystals. The bowl-to-bowl
      inversion dynamics of these buckybowls can be classified into two types; one has
      a planar transition structure, whereas the other has an S-shaped transition
      structure. A larger longitudinal length of these buckybowls corresponds to a
      stronger preference for the latter. The photophysical properties of these
      buckybowls were examined and compared with those of C60 and C70 . Buckybowls 5
      have absorption bands at wavelengths greater than 450 nm, which are similar to
      those of C70 . The chiral resolution of the mono-substituted buckybowl 4 ac was
      also studied by using HPLC with a chiral column. 

PMID- 24311154
TI  - Exploitation of induced 2n-gametes for plant breeding.
AB  - Unreduced gamete formation derived via abnormal meiotic cell division is an
      important approach to polyploidy breeding. This process is considered the main
      driving force in spontaneous polyploids formation in nature, but the potential
      application of these gametes to plant breeding has not been fully exploited. An
      effective mechanism for their artificial induction is needed to attain greater
      genetic variation and enable efficient use of unreduced gametes in breeding
      programs. Different approaches have been employed for 2n-pollen production
      including interspecific hybridization, manipulation of environmental factors and
      treatment with nitrous oxide, trifluralin, colchicine, oryzalin and other
      chemicals. These chemicals can act as a stimulus to produce viable 2n pollen;
      however, their exact mode of action, optimum concentration and developmental
      stages are still not known. Identification of efficient methods of inducing 2n
      gamete formation will help increase pollen germination of sterile interspecific
      hybrids for inter-genomic recombination and introgression breeding to develop new
      polyploid cultivars and increase heterozygosity among plant populations.
      Additionally, the application of genomic tools and identification and isolation
      of genes and mechanisms involved in the induction of 2n-gamete will enable
      increased exploitation in different plant species, which will open new avenues
      for plant breeding.

PMID- 24311156
TI  - The French regional issue of mass spectrometry reviews.

PMID- 24311155
TI  - Generation of selectable marker-free transgenic eggplant resistant to Alternaria
      solani using the R/RS site-specific recombination system.
AB  - KEY MESSAGE: Marker-free transgenic eggplants, exhibiting enhanced resistance to
      Alternaria solani , can be generated on plant growth regulators (PGRs)- and
      antibiotic-free MS medium employing the multi-auto-transformation (MAT) vector,
      pMAT21 - wasabi defensin , wherein isopentenyl transferase ( ipt ) gene is used
      as a positive selection marker. ABSTRACT: Use of the selection marker genes
      conferring antibiotic or herbicide resistance in transgenic plants has been
      considered a serious problem for environment and the public. Multi-auto
      transformation (MAT) vector system has been one of the tools to excise the
      selection marker gene and produce marker-free transgenic plants. Ipt gene was
      used as a selection marker gene. Wasabi defensin gene, isolated from Wasabia
      japonica (a Japanese horseradish which has been a potential source of
      antimicrobial proteins), was used as a gene of interest. Wasabi defensin gene was
      cloned from the binary vector, pEKH-WD, to an ipt-type MAT vector, pMAT21, by
      gateway cloning technology and transferred to Agrobacterium tumefaciens strain
      EHA105. Infected cotyledon explants of eggplant were cultured on PGRs- and
      antibiotic-free MS medium. Extreme shooty phenotype/ipt shoots were produced by
      the explants infected with the pMAT21-wasabi defensin (WD). The same PGRs- and
      antibiotic-free MS medium was used in subcultures of the ipt shoots.
      Subsequently, morphologically normal shoots emerged from the Ipt shoots.
      Molecular analyses of genomic DNA from transgenic plants confirmed the
      integration of the WD gene and excision of the selection marker (ipt gene).
      Expression of the WD gene was confirmed by RT-PCR and Northern blot analyses. In
      vitro whole plant and detached leaf assay of the marker-free transgenic plants
      exhibited enhanced resistance against Alternaria solani.

PMID- 24311157
TI  - The lipids in photoautotrophic and heterotrophic cell suspension cultures of
      Chenopodium rubrum.
AB  - Resembling the lipids in the leaves and other green organs of intact plants, the
      lipids in photoautotrophic cell cultures of Chenopodium rubrum were found to
      contain high proportions of monogalactosyldiacylglycerols and
      digalactosyldiacylglycerols, as well as fair amounts of
      sulfoquinovosyldiacylglycerols and diacylglycerophosphoglycerols. Conversely, the
      heterotrophic cell cultures, from which the photoautotrophic cultures had been
      derived, contained only traces of these compounds. The heterotrophic cultures
      were rich in sterols, sterol esters, sterol glycosides, and esterified sterol
      glycosides. The lipids of photoautotrophic cell cultures contained higher
      proportions of constituent linolenic acid, but lower concentrations of linoleic
      acid than those of heterotrophic cultures. In the photoautotrophic cultures, as
      in green leaves, linolenic acid was predominantly estrified in
      monogalactosyldiacylglycerols and digalactosyldiacylglycerols. This investigation
      shows that it is possible to select strains of cell cultures, which are capable
      of grosing photoautotrophically, with the aim of activating the biosynthesis of
      specific metabolites. 

PMID- 24311158
TI  - Fatty-acid composition and biosynthesis in cell suspension cultures of Glycine
      max (L.) Merr., Catharanthus roseus G. Don and Nicotiana tabacum L.
AB  - The fatty-acid composition of C. roseus and N. tabacum cell suspension cultures
      was unaffected by subculture on Wood and Braun, Murashige and Skoog, or Gamborg
      B5C media. However, placing the cultures - which were normally grown at 25
      degrees  C - at 15 degrees  C reduced growth but resulted in enhanced formation
      of oleic and linolenic acids in C. roseus cultures and increased levels of
      linoleic and linolenic acids in cultures of G. max and N. tabacum, respectively.
      The incorporation of [(14)C]acetate into [(14)C]linoleic acid was more rapid in
      N. tabacum cells than in G. max cells, but was very poor in C. roseus where the
      [(14)C] label was distributed mainly between palmitic and oleic acids. 

PMID- 24311159
TI  - The effect of different temperatures on fatty-acid synthesis and polyunsaturation
      in cell suspension cultures.
AB  - Cell suspension cultures of Catharanthus roseus G. Don, Glycine max (L.) Merr.
      and Nicotiana tabacum L. were incubated with [(14)C]acetate, [(14)C]oleic acid
      and [(14)C]linoleic acid at five different temperatures ranging from 15 to 35
      degrees  C. When the incubation temperature was increased, [(14)C]acetate was
      incorporated preferentially into [(14)C]palmitate, with a concomitant drop in
      [(14)C]oleate formation. Between 15 and 20 degrees  C, [(14)C]oleic acid
      accumulated in C. roseus cells. In all cultures, optimum desaturation of
      [(14)C]oleic acid to [(14)C]linoleic acid occurred between 20 and 25 degrees  C,
      and in G. max this was also the optimal range for desaturation of [(14)C]linoleic
      acid to [(14)C]linolenic acid. Elongation of [(14)C]palmitic acid was inhibited
      when cultures grown at 15 degrees  C for 25 h were subsequently incubated with
      [(14)C]acetate at 25 degrees  C. [(14)C]oleic acid accumulated in G. max and C.
      roseus cultures grown at 35 degrees  C for 25 h and subsequently incubated at 25
      degrees  C. Desaturation of [(14)C]oleic acid increased up to 25 degrees  C, but
      then decreased or leveled off depending on the cell line and on the temperature
      prior to incubation. 

PMID- 24311160
TI  - Electrical field effects induced in membranes of developing chloroplasts.
AB  - Etioplasts, etiochloroplasts, and chloroplasts of Avena sativa L. purified on a
      Percoll gradient were subjected to increasing electric field strengths in the
      orifice of a hydrodynamically focussing Coulter Counter. The change in resistance
      of the orifice when an organelle is present correlates well with the size of the
      plastid for field strengths up to about 3.5 kV cm(-1). Beyond this field
      strength, depending on the size of the organelle, the size is underestimated. The
      underestimation of the size is caused by the dielectric breakdown of the envelope
      membranes once a critical membrane potential has been exceeded. Beyond breakdown
      the signal of the particle is predominately determined both by the internal
      conductivity and the increased membrane conductivity. Measurements of the
      breakdown voltage of different developmental stages of the plastids reveal that
      the breakdown voltage decreases from 1.2 V in etioplasts to about 0.9 V in
      chloroplasts after 48 h illumination. The decrease in breakdown voltage can be
      explained in terms of increasing incorporation of proteins into the inner
      envelope membrane during development.This view is consistent with conclusions
      drawn by other authors from transport and biochemical studies. The
      underestimation of the size beyond breakdown is about 20% and increases to a
      constant value of about 40% during the first 3 h of illumination. The
      underestimation decreases again to about 10% when the chloroplast stage is
      reached. This result is consistent with the current view of chloroplast
      development. Mobilisation of glucans, the transformation of the prolamellar body
      of etioplasts into thylacoid membranes as well as an intensive synthesis of
      pigments and enhanced rates of ions transport in the first hour of illumination
      gives rise to an increased pool of ionic compounds within the plastid stroma.It
      should be noted that purification of the plastids on Percoll gradient leads to
      size distributions which are almost normally distributed over the whole field
      range, suggesting that the preparations are also electrically homogeneous (U.
      Zimmermann, F. Riemann and G. Pilwat: Biochim. Biophys. Acta 436, 460-474
      (1976)). In contrast with results of Lurssen, K., Z. Naturforsch. 25b, 1113-1119
      (1970) only a slight increase of the modal volume from the etioplast stage to the
      chloroplast stage is observed. 

PMID- 24311161
TI  - Polarity and growth of caulonema tip cells of the moss Funaria hygrometrica.
AB  - In the caulonema tip cells of Funaria hygrometrica, chloroplasts, mitochondria,
      and dictyosomes have differences in structure which are determined by cell
      polarity. In contrast to the slowly growing chloronema tip cells the apical cell
      of the caulonema contains a tip body. Colchicine stops tip growth; it causes the
      formation of subapical cell protrusions, redistribution of the plastids, and a
      loss of their polar differentiation. Cytochalasin B inhibits growth and affects
      the position of cell organelles. After treatment with ionophore A23 187, growth
      is slower and shorter and wider cells are formed. D2O causes a transient
      reversion of organelle distribution but premitotic nuclei are not dislocated. In
      some tip cells the reversion of polarity persists; they continue to grow with a
      new tip at their base. During centrifugation, colchicine has only a slight
      influence on the stability of organelle anchorage. The former polar organization
      of most cells is restored within a few hours after centrifugation, and the cells
      resume normal growth. In premitotic cells the nucleus and other organelles cannot
      be retransported, they often continue to grow with reversed polarity. Colchicine
      retards the redistribution of organelles generally and increases the number of
      cells that form a basal outgrowth. The interrelationship between the peripheral
      cytoplasm and the nucleus and the role of microtubules in maintaining and
      reestablishing cell polarity are discussed. 

PMID- 24311162
TI  - Expression of nuclear and chloroplastic genes coding for fraction-1 protein in
      somatic hybrids of Nicotiana tabacum + rustica.
AB  - In the sexual interspecific cross, Nicotiana rustica L.xN. tabacum L., N. rustica
      can serve as the female but not as the male parent. By fusion of protoplasts, the
      barrier to fertilization was overcome and somatic hybrids containing N. tabacum
      cytoplasm were produced as shown by isoelectric focusing of the Fraction-1
      protein (F-1-protein). All somatic hybrids displayed polypeptides of the large
      subunit of F-1 protein (which is coded by the chloroplast genome) characteristic
      of only one or the other parental species. Two hybrids had large subunits of the
      N. tabacum type and two hybrids had those of the N. rustica type. Three hybrids
      contained three smallsubunit polypeptides (coded by the nuclear genome), one
      being characteristic of N. rustica, one characteristic of N. tabacum, and one
      with an isoelectric point common to both species. A fourth hybrid contained only
      two small-subunit polypeptides of the N. tabacum type but in a F-1 protein
      macromolecule whose large subunits were of the N. rustica type. One somatic
      hybrid was self-fertile and its F2 progeny contained large- and small-subunit
      polypeptides indistinguishable in their isoelectric points from those in the
      parent F1 hybrid. All somatic hybrids showed an aneuploid chromosome number and
      morphological characteristics intermediate between those of N. rustica and N.
      tabacum. 

PMID- 24311163
TI  - Effects of blue and red light on unrolling of rice leaves.
AB  - Unrolling of the second leaf of 8-day-old rice (Oryza sativa L.) seedlings was
      promoted by weak blue light (B), but not by red light (R). The effect of B was
      counteracted by irradiation with R just before or after the B. The counteracting
      effect of R was reversed by subsequent irradiation with far-red light but not by
      B, even if B was applied for 10 h. The B was effective when the region 0.5-2 cm
      from the tip of the leaf was irradiated. These results indicate that in rice
      photoreceptors for blue light located in the region 0.5-2 cm from the tip of the
      leaf play a key role in leaf unrolling and that a B-absorbing pigment and
      phytochrome participate in leaf unrolling in a closely related manner. 

PMID- 24311164
TI  - Regulators of cell division in plant tissues : XXVIII. Metabolites of zeatin in
      sweet-corn kernels: Purifications and identifications using high-performance
      liquid chromatography and chemical-ionization mass spectrometry.
AB  - The cytokinins in certain fractions prepared from extracts of immature sweet-corn
      (Zea mays L.) kernels using polystyrene ion-exchange resins have been further
      investigated. Cytokinins active in the radish cotyledon bioassay were purified
      from these fractions and identified as 9-beta-D-glucopyranosylzeatin, 9-beta-D
      glucopyranosyldihydrozeatin, O-beta-D-glucopyranosylzeatin. and O-beta-D
      glucopyranosyl-9-beta-D-ribofuranosylzeatin. In addition, compounds which
      resemble zeatin and its glycosides in chromatographic behaviour and in
      ultraviolet absorption characteristics were purified from extracts of the same
      material by high-performance liquid chromatography. In addition to zeatin and
      zeatin riboside, the following compounds were identified unambiguously: O-beta-D
      glucopyranosyl-9-beta-D-ribofuranosyldihydrozeatin, O-beta-D
      glucopyranosyldihydrozeatin, and hihydrozeatin riboside. A further compound was
      tentatively identified as O-beta-D-glucopyranosylzeatin, and at least two
      unidentified compounds appeared to be new derivatives of zeatin. In identifying
      the above compounds, chemical-ionization mass spectrometry proved to be an
      invaluable complementary technique, yielding spectra showing intense protonated
      molecular-ion peaks and also prominent structure-related fragmentation that was
      either not evident or very minor in the electron-impact spectra. An assessment of
      the relative importance of the various possible mechanisms for cytokinin
      modification and inactivation in mature sweet-corn kernels was made by supplying
      [(3)H]zeatin and [(3)H]zeatin riboside to such kernels after excision. The
      principal metabolites of zeatin were adenine nucleotides, adenosine and adenine,
      while little of the metabolite radioactivity was attributable to known O
      glucosides. Adenine nucleotides and adenine were the principal metabolites of
      zeatin riboside, while lesser metabolites were identified as adenosine,
      dihydrozeatin, and the O-glucosides of dihydrozeatin and dihydrozeatin riboside.
      Side-chain cleavage, rather than side-chain modification, appears to be the
      dominant form of cytokinin metabolism in mature sweet-corn kernels. 

PMID- 24311165
TI  - Role of alpha-galactosidase in osmotic regulation of Poterioochromonas
      malhamensis.
AB  - In Poterioochromonas malhamensis, osmotic regulation is mainly mediated by the
      formation and degradation of isofloridoside (alpha-galactosyl-1->1-glycerol). In
      cell homogenates an alpha-galactosidase can be demonstrated. About one hour after
      an increase in external osmotic pressure, the enzyme activity increases. external
      osmotic pressure, the enzyme activity increases. The increase is more pronounced
      with a higher osmotic change and appears to be due to de novo synthesis of the
      enzyme, as it can be prevented by preincubation with actinomycin D or actidion.
      When the increase in alpha-galactosidase was suppressed with actinomycin D, the
      in vivo degradation rate of isofloridoside was slowed down. These results
      indicate a function of the alpha-galactosidase in osmotic regulation. 

PMID- 24311166
TI  - Aminoacylation of four tRNA species in lupin (Lupinus luteus) cotyledons.
AB  - During germination of lupin seeds, the levels of in-vivo tRNA aminoacylation
      increase in different ways, depending on the species of tRNA. Column
      chromatography of tRNA on reverse-phase-chromatography (RPC-5) has shown the
      presence of 4 peaks of isoleucyl-tRNA, 5 of leucyl-tRNA, 5 of lysyl-tRNA, 2 of
      tyrosyl-tRNA, and 4 of valyl-tRNA. Cochromatography of periodate treated and
      control tRNA preparations, labeled with radioactive amino acids, indicates
      identical aminoacylation in vivo of isoaccepting tRNAs during plant development.
      One isoacceptor of isoleucine tRNA changes its elution profile after periodate
      treatment. 

PMID- 24311167
TI  - Fruit-set of unpollinated ovaries of Pisum sativum L. : Influence of vegetative
      parts.
AB  - The influence of removing the apical shoot and different leaves above and below
      the flower on the fruit-set of unpollinated pea ovaries (Pisum sativum L. cv.
      Alaska) has been studied. Unpollinated ovaries were induced to set and develop
      either by topping or by removing certain developing leaves of the shoot. Topping
      had a maximum effect when carried out before or on the day of anthesis, and up to
      four consecutive ovaries were induced to set in the same plant. The inhibition of
      fruit-set was due to the developing leaves and not to the apex. The third leaf
      above the first flower, which had a simultaneous development to the ovary, had
      the stronger inhibitory effect on parthenocarpic fruit-set. The application of
      different plant-growth regulators (indoleacetic acid, naphthylacetic acid, 2,4
      dichlorophenoxyacetic acid, gibberellic acid, benzyladenine and abscisic acid)
      did not mimic the negative effect of the shoot. 

PMID- 24311168
TI  - Fruit-set of unpollinated ovaries of Pisum sativum L. : Influence of plant-growth
      regulators.
AB  - The development of parthenocarpic fruits of Pisum sativum L. cv. Alaska was
      induced by the application of different plant-growth regulators in aqueous
      solution to the emasculated ovaries in untopped plants. At least one compound in
      each of the groups of auxins (2,4-dichlorophenoxyacetic acid), cytokinins
      (benzyladenine), and gibberellins (gibberellic acid) was found active.
      Gibberellic acid (GA3), however, was the only substance which produced pods
      similar to those of fruits with seeds. The length of the pods obtained by GA3 was
      a linear function of the logarithm of the concentration of GA3 in the solution.
      The effect of GA3 (at a concentration which produced 50% of the maximum pod
      length) was enhanced by a simultaneous application of 2,4-dichlorophenoxyacetic
      acid. Abscisic acid (ABA) counteracted the effect of GA3 and of topping. The
      results suggest that gibberellins and ABA may exert a major regulatory control in
      natural fruit-set. Peas can be used for the assay of fructigenic activity and is
      an advantageous material for the study of the mode of action of gibberellins on
      fruit-set. 

PMID- 24311169
TI  - pH-Dependent accumulation of indoleacetic acid by corn coleoptile sections.
AB  - The uptake of auxin by 1-mm slices of corn (Zea mays L.) coleoptiles, a tissue
      known to transport auxin polarly, depends on the pH of the medium. Short-term
      uptake of indole-3-acetic acid (IAA) in coleoptiles increases with decreasing pH
      of the buffer as would be expected if the undissociated weak acid, IAA.H, were
      more permeable than the auxin anion, IAA(-), and IAA(-) accumulates in the
      tissues because of the higher pH of the cytoplasm. Although uptake of [(3)H]IAA
      is reduced in neutral buffers, it is greater than expected if it were limited to
      just the extracellular space of the tissue. The radioactivity accumulated by the
      tissue can be quantitatively extracted by organic solvents and identified as IAA
      by thin-layer chromatography. The tissue radioactivity is freely mobile and can
      efflux from the tissue. Thus these cells in pH 5 buffer are able to retain an
      average internal concentration of mobile IAA that is at least several times
      greater than the external concentration. A prominent feature of auxin uptake from
      acidic buffers is enhanced accumulation at high auxin concentration. This
      indicates that, in addition to fluxes of IAA.H, a saturable site is involved in
      auxin uptake. Whenever the auxin-anion gradient is directed outward, saturating
      the efflux of auxin anions increases accumulation. Furthermore, the observed
      slowing of short-term uptake of radioactive IAA by increasing concentrations of
      IAA or K(+) indicates either an activation of the presumptive auxin leak or
      saturation of another carrier-mediated uptake system such as a symport of auxin
      anions with protons. By contrast in neutral buffers, effects of concentration on
      uptake rates disappear. This implies that at neutral pH the anion leak is
      decreased and influx depends on the symport. 

PMID- 24311170
TI  - The role of peroxidase isoenzyme groups of Nicotiana tabacum in hydrogen peroxide
      formation.
AB  - Three peroxidase isoenzyme-groups found in cell walls of tobacco were tested for
      their capacity to form H2O2. Isoenzyme-group GI, located only in cell walls (GII
      and GIII are also found in protoplasts) showed the highest Kapp-value for H2O2
      formation. The lowest Kapp-value, i.e., maximal H2O2-formation was received for
      group GIII which is ionically bound to the cell wall. As shown before, GI yields
      maximal polymerization rates for coniferyl- and p-coumarylalcohol. These facts
      indicate that each of the peroxidase isoenzyme groups of the cell wall is
      involved with different catalytic functions within the same pathways of H2O2
      formation and succeeding lignification. H2O2-formation catalyzed by all 3 groups
      was increased by very low concentrations of Mn(2+)-ions. The required amount of
      Mn(2+) leading to maximal stimulation was in each case dependent on the basic
      rate of H2O2-formation. Maximal stimulation of H2O2-formation by phenolic
      compounds was achieved by coniferylalcohol at a concentration of 10(-4)M for all
      groups. Stimulation by p-coumaryl-and by sinapylalcohol was not as significant. 

PMID- 24311171
TI  - Hexose transport and membrane depolarization in Riccia fluitans.
AB  - In the aquatic liverwort Riccia fluitans, the uptake of (14)C-labeled 3-O-methyl
      glucose (3-OMG) and membrane depolarization (DeltaPsi m ) caused by different
      hexoses has been studied as a function of time and concentration of hexose, K(+)
      and H(+), respectively. The rate of uptake of the non-metabolized 3-OMG shows two
      components: (A)A pH-dependent saturable uptake with a km value around 0.1 mM
      which saturates at 2.1 and 7.2 MUmol G DW (-1) h(-1) at pH 6.8 and 5.0,
      respectively; and (B) a pH-insensitive uptake component which increases linearly
      with the external 3-OMG concentration and does not saturate ?4 mM. Hexoses
      rapidly depolarize the plasmalemma of the thallus cell and increase its
      electrical conductance. The maximal DeltaPsi m was 60+/-2 mV, the concentrations
      (mM) for half-maximal DeltaPsi m were 0.24 glucose, 0.32 galactose, 0.37 2-deoxy
      glucose, 0.38 3-OMG, 0.57 mannose, and 34 fructose. In terms of a hexose carrier
      model and an equivalent circuit for the hexose-induced depolarized state of the
      membrane, it is proposed that a hexose carrier operates either electrogenically
      in its protonated, pH-and voltage-sensitive state, or by transmembrane diffusion
      of its uncharged state. 

PMID- 24311172
TI  - Cell organelles from crassulacean acid metabolism (CAM) plants : II.
      Compartmentation of enzymes of the crassulacean acid metabolism.
AB  - The intracellular distribution of enzymes involved in the Crassulacean acid
      metabolism (CAM) has been studied in Bryophyllum calycinum Salisb. and Crassula
      lycopodioides Lam. After separation of cell organelles by isopycnic
      centrifugation, enzymes of the Crassulacean acid metabolism were found in the
      following cell fractions: Phosphoenolpyruvate carboxylase in the chloroplasts;
      NAD-dependent malate dehydrogenase in the mitochondria and in the supernatant;
      NADP-dependent malate dehydrogenase and phosphoenolpyruvate carboxykinase in the
      chloroplasts; NADP-dependent malic enzyme in the supernatant and to a minor
      extent in the chloroplasts; NAD-dependent malic enzyme in the supernatant and to
      some degree in the mitochondria; and pyruvate; orthophosphate dikinase in the
      chloroplasts. The activity of the NAD-dependent malate dehydrogenase was due to
      three isoenzymes separated by (NH4)2SO4 gradient solubilization. These isoenzymes
      represented 17, 78, and 5% of the activity recovered, respectively, in the order
      of elution. The isoenzyme eluting first was associated with the mitochondria and
      the second isoenzyme was of cytosolic origin, while the intracellular location of
      the third isoenzyme was probably the peroxisome. Based on these findings, the
      metabolic path of Crassulacean acid metabolism within cells of CAM plants is
      discussed. 

PMID- 24311173
TI  - On the use of Avena protoplasts to study chloroplast development.
AB  - Different methods were tested to isolate protoplasts from etiolated, partially
      greened, and light-grown leaves of Avena sativa. Preparations with high yields
      and high photosynthetic capacities (time of illumination ?4 h) were obtained when
      small transverse leaf segments were incubated for 2 h at 30 degrees C in 2%
      cellulysin (Calbiochem), 0.6 M mannitol, and 0.5% bovine serum albumin (BSA) at
      pH 5.6, without shaking. As measured by light-dependent O2 evolution or fixation
      of labeled bicarbonate, protoplasts exhibited rates of up to 124 MUmol per mg of
      chlorophyll per h at 20 degrees C and saturating bicarbonate, which were nearly
      identical to those found with intact leaves. The assay conditions necessary for
      this activity were 0.6 M sorbitol, 50 mM N-2-hydroxy-ethylpiperazine-N'-2-ethane
      sulfonic acid (pH 7.6), and 10 mM NaHCO3. If plastids were isolated from these
      protoplasts, sorbitol was 0.45 M, including 10 mM ethylenediaminetetraacetate
      (EDTA). under these conditions, rates of photosynthesis were up to 125 (light
      grown) and 71 (6 h illuminated) MUmol O2 evolved or (14)CO2 fixed per mg of
      chlorophyll per h, compared to 3.5 MUmol.mg chl(-1).h(-1) obtained with
      mechanically isolated plastids. With this system, CO2-dependent O2 evolution was
      already detected after 3 h of illumination of etiolated tissue, but could only be
      observed at pH values between 7.6 and 8.6, in the presence of EDTA. At lower pH
      (7.3) or at pH 7.6 in the absence of EDTA, light-dependent O2 evolution up to 24
      h of greening was only measurable with 3-phosphoglycerate as the substrate. The
      possible effects of EDTA in this respect as well as the advantages of using
      protoplasts or plastids isolated from protoplasts for developmental studies are
      discussed. 

PMID- 24311174
TI  - Promotion of mesocotyl growth in etiolated rice seedlings by 4-ethoxy-1-(p-tolyl)
      s-triazine-2,6(1H,3H)-dione.
AB  - 4-Ethoxy-1-(p-tolyl)-s-triazine-2,6(1H,3H)-dione (TA) promoted mesocotyl growth
      in dark-grown rice (Oryza sativa L.) seedlings. In cultivars of the japonica type
      TA alone showed a small promotive effect and TA+gibberellic acid(GA3) had a
      marked synergistic effect, while in other cultivars, mostly of the indica type,
      TA alone showed a great promotive effect and TA+GA3 had only an additive effect.
      In cv. Nato, a typical representative of cultivars showing the second type of
      response, the concentration of TA giving the greatest growth promotion was around
      0.1-0.2 mM. In Nato seedlings treated with TA at 0.1 mM, the mesocotyls continued
      to elongate for 6 days and reached about 75 mm in length, while the mesocotyls of
      control seedlings grew to a maximum of about 10 mm and growth was limited to the
      first 3 days after planting. The TA-induced mesocotyl elongation was mainly the
      consequence of increased cell multiplication in the meristematic area immediately
      below the coleoptilar node. GA3, abscisic acid (ABA) and ethylene also stimulated
      mesocotyl growth in dark-grown Nato seedlings but their effects were much smaller
      than those of TA. ABA, like GA3, had an additive effect with TA, but ethylene
      suppressed the effect of TA and resulted in increased lateral expansion in the
      upper region of the mesocotyls of TA-treated seedlings. 

PMID- 24311175
TI  - Microtubules, protoplasts and plant cell shape : An immunofluorescent study.
AB  - Indirect immunofluorescence has been used to study the function of cytoplasmic
      microtubules in controlling the shape of elongated carrot cells in culture. Using
      a purified wall-degrading preparation, the elongated cells are converted to
      spherical protoplasts and the transverse hoops of bundled microtubules are
      disorganised but not depolymerised in the process. Since microtubules remain
      attached to fragments of protoplast membrane adhering to coverslips and are still
      seen to be organised laterally in bundles, it would appear that re-orientation of
      the transverse bundles is due to loss of cell wall and not to the cleavage of
      microtubule bridges. After 24 h treatment in 10(-3) M colchicine, microtubules
      are depolymerised in elongated cells but, at this time, the cells retain their
      elongated shape. This suggests that wall which was organised in the presence of
      transverse microtubule bundles can retain asymmetric shape for short periods in
      the absence of those tubules. However, after longer periods of time the cells
      become spherical in colchicine. Neither wall nor tubules therefore exert
      individual control on continued cellular elongation and so we emphasize the
      fundamental nature of wall/microtubule interactions in shape control. It is
      concluded that the observations are best explained by a model in which hooped
      bundles of microtubules-which are directly or indirectly associated with
      molecules involved with cellulose biosynthesis at the cell surface-act as an
      essential template or scaffolding for the orientated deposition of cellulose. 

PMID- 24311176
TI  - New lepidopteran sex attractants found by systematic field screening of blends
      containing (Z)-11- and (E)-11-tetradecenal.
AB  - By screening (Z)-11-tetradecenal and (E)-11-tetradecenal alone, mixed with each
      other or mixed with corresponding alcohols or acetates, sex attractants were
      discovered or improved for nine Lepidoptera. Attractants were found forAcleris
      sparsana, A. tripunctana, Aphelia viburnana (all Tortricidae),Cilix glaucata
      (Drepanidae), andCosmia trapezina (Noctuidae). The significance of Delta11
      tetradecenals in tortricid sex attractants is discussed. 

PMID- 24311177
TI  - 9,11-Dodecadienyl alcohols, acetates, or aldehydes as synthetic chemical sex
      attractants for four Lepidoptera:Cosmopterix gemmiferella (Clemens),Dichrorampha
      simulana (Clemens),Tortricidia testacea (Packard), and anAncylis sp.
AB  - Four lepidoptera were lured to field traps containing various combinations of
      9,11-dodecadienes with alcohol, acetate, or aldehyde functional groups. All
      species required two chemical components for best attraction.Cosmopterix
      gemmiferella was most responsive to a combination of (9Z)-9,11-dodecadienyl
      acetate and (9E)-9,11-dodecadienyl acetate in 2?1 ratio;Dichrorampha simulana to
      (9E)-9,11-dodecadienyl acetate and (9E)-9,11-dodecadien-1-ol in 10?1
      ratio;Tortricidia testacea to (9Z)-9,11-dodecadienal and (9E)-9,11-dodecadienal
      in 10?1 ratio; andAncylis sp. to (9Z)-9,11-dodecadienyl acetate and (9Z)-9,11
      dodecadien-1-ol in 10?1 ratio. 

PMID- 24311178
TI  - Synergism between myristicin and xanthotoxin, a naturally cooccurring plant
      toxicant.
AB  - Myristicin, a methylenedioxyphenyl (MDP)-containing phenylpropene constituent of
      the leaves of many plants in the family Umbelliferae, is a highly effective
      Synergist of the cooccurring furanocoumarin xanthotoxin. As little as 0.10 % in
      an artificial diet can increase the toxicity of xanthotoxin toHeliothis zea
      (Lepidotera: Noctuidae) fivefold. In addition to increasing the proportion of
      caterpillars dying at a given xanthotoxin concentration, myristicin also
      increases the rate at which they die and increases the time to molt of surviving
      larvae. That there was no increase in the deterrency of xanthotoxin in the
      presence of myristicin suggests that the mechanism of synergism is not
      behaviorial but rather is biochemical, via MDP competitive inhibition of
      microsomal mixed function oxidases. 

PMID- 24311179
TI  - Multiple acceptors for pheromonal enantiomers on single olfactory cells in the
      Douglas-fir beetle,Dendroctonus pseudotsugae Hopk. (Coleoptera: Scolytidae).
AB  - Olfactory perception of pheromonal enantiomers by male and female Douglas-fir
      beetles,Dendroctonus pseudotsugae Hopk. (Coleoptera: Scolytidae), was
      investigated by electrophysiological techniques and behavioral bioassays.
      Electroantennograms (EAGs) and single-cell responses indicated both sexes to be
      more responsive to racemic frontalin and the (-)-enantiomer at lower dosages. At
      higher dosages, little difference was noted in responses to either enantiomer.
      However, response to the racemic mixture at higher dosages was slightly greater
      than responses to either enantiomer alone. In laboratory behavioral bioassays,
      responses to low concentrations of (-)-frontalin and the racemic mixture exceeded
      response to the (+)-enantiomer alone. At a higher concentration, responses to the
      racemic mixture or either enantiomer alone did not differ. The results indicate
      that separate enantiomer-specific acceptors may exist on the same pheromone
      receptor cell. 

PMID- 24311180
TI  - Synthesis of stereoisomers of 8-methyl-2-decanol and esters attractive to
      severalDiabrotica sp.
AB  - Details of the syntheses of the four stereoisomers of 8-methyl-2-decanol and its
      propanoate ester are given. The racemic ester, two of its stereoisomers, and one
      stereoisomer as an acetate are attractive to several species ofDiabrotica. The
      key steps in the syntheses involve high-performance liquid chromatograpic
      resolutions of diastereomers to achieve high configurational enrichment of each
      site and generation of (R)-2-methylbutyric acid by chemical degradation ofD
      isoleucine. 

PMID- 24311181
TI  - Field trapping of threeEpinotia species with (Z,Z)-7,9-dodecadienyl acetate
      (Lepidoptera: Tortricidae).
AB  - Field survey of the geometrical isomers of 7,9-dodecadienyl alcohol, acetate, and
      aldehyde has resulted in attractants and inhibitors for three species of
      tortricid moths.Epinotia silvertoniensis and an undescribedEpinotia sp. were all
      attracted to (Z,Z)-7,9-dodecadienyl acetate. AnotherEpinotia sp. was attracted to
      (Z,Z)-7,9-dodecadienyl acetate and (Z,Z)-7,9-dodecadien-1-ol. Electroantennogram
      data and inhibition patterns for one of theEpinotia sp. are also reported. In
      addition,E. criddleana was attracted to lures containing (E)-9-dodecenyl acetate.

PMID- 24311182
TI  - Multichemical defense of plant bugHotea gambiae (Westwood) (Heteroptera:
      Scutelleridae): (E)-2-hexenol from abdominal gland in adults.
AB  - The occurrence inHotea gambia adults of a sexual dimorphism in the divided dorsal
      abdominal scent gland (dg 1)is reported. Counts made of ducted secretory units
      indicate that female dg 1 regresses at the end of larval development, unlike male
      dg 1 which undergoes no regression. Other dorsal abdominal scent glands (dg 2, dg
      3) which function in the larvae cease to function during the imaginai moult. From
      gas chromatographic, mass spectrometric and [(1)H]NMR data, the identity of the
      secretion from male adult dg 1 was established as virtually pure (E)-2-hexenol (a
      100-mg mature male adult contains 0.5-1 MUl of secretion). 2-Hexenol was also
      found in the reduced female adult dg 1. In the sexually monomorphic metathoracic
      scent gland, (E)-2-alkenals (C6, C8) and (E)-4-oxohex-2-enal, together with
      monoterpenes (beta-pinene, limonene) but not 2-hexenol, were identified. The
      vapor of (E)-2-hexenol is repellent to both sexes ofHotea adults and toxic to
      blowfly (Calliphora) eggs. 

PMID- 24311183
TI  - Inhibition of seedling growth of crop species by recirculating root exudates
      ofBidens pilosa L.
AB  - The allelopathic effects of root exudates ofBidens pilosa L. on seedling growth
      ofLactuca sativa L.,Phaseolus vulgaris L.,Zea mays L., andSorghum bicolor (L.)
      Moench were studied using a root exudate recirculating system that allows
      continuous exposure of crop plants to allelopathic chemicals. This system
      maintains an undisturbed rhizosphere and eliminates competition and physical
      contact between the donor and acceptor plants. Comparison of responses to
      hydrophobic and hydrophilic root exudates is made possible by removal of
      hydrophobic compounds using XAD-4. Treatments consisted ofB. pilosa, B. pilosa
      with an Amberlite XAD-4 resin column attached to the donor pot to remove
      hydrophobic allelochemicals, and a donor pot without weeds.B. pilosa
      significantly inhibited seedling growth of all crop species tested. The crop
      species varied in response to the root exudates, withL. sativa being most
      sensitive. Larger and olderB. pilosa plants caused greater inhibition of seedling
      growth ofL. sativa andP. vulgaris than did smaller (younger)B. pilosa plants.B.
      pilosa with XAD-4 caused significantly less inhibition to all crop species,
      exceptZ. mays, thanB. pilosa without XAD-4, indicating that the hydrophobic
      exudates played an important role in the allelopathic growth inhibition.
      Variability in species response toB. pilosa with and without XAD-4 was probably
      due to differences in sensitivity to hydophobic and hydrophilic allelochemicals. 

PMID- 24311184
TI  - Influence of the olfactory sense upon smolt transformation in salmonid fishes.
AB  - The effect of olfactory deprivation on the process of smolt transformation in
      Atlantic salmon (Salmo salar L.) was investigated. Salmon parr were rendered
      anosmic by heat-cauterizing in November, and, together with controls, size,
      purine deposition (silvering), and mortality were monitored throughout spring in
      individuals within sibling groups. In May the fish were exposed to seawater (3.2%
      salinity) to determine levels of smoking in anosmic fish compared with control
      fish. Olfactory deprivation was found to induce a negative effect on survival in
      both anosmic fish as well as controls when reared within the same rearing tank. A
      54% survival was metered in anosmic fish as opposed to only 26% survival in
      control fish during the experimental period. The low survival rates observed are
      suggested to result from abnormal behavior in anosmic fish due to lack of proper
      olfactory stimuli. Within each strain, the anosmic fish were found shorter and
      displayed less-silvering than their control fish at the end of the experimental
      period. Further, since control fish could withstand salinity exposure longer than
      anosmic fish, smolting is suggested to have been retarded among the anosmic fish.
      Olfactory influence on smolt transformation may be caused by conspecific
      pheromones secreted for the purpose of mediating effects of life-history patterns
      in salmonid fishes. 

PMID- 24311185
TI  - Insect antifeedant activity of clerodane diterpenoids against larvae ofSpodoptera
      Littoralis (Boisd.) (Lepidoptera).
AB  - Antifeedant activities of nine clerodane diterpenoids, isolated in this
      laboratory from different species ofAjuga plants, have been studied against
      larvae of Egyptian cotton leafwormSpodoptera littoralis (Boisd.) (Lepidoptera) by
      application of the leaf disk method. Evaluation of activity was carried out by
      calculating, at different time intervals, the feeding ratio (FR) from the
      relationship between the consumed areas of treated disks (CTD) and control disks
      (CCD); for comparison purposes a FR50 defined as the FR at a CCD of 50% was
      established. Some compounds exhibited activity at a 0.01 MUg/cm(2) dose (0.3
      ppm). Structure-activity relationships are discussed. 

PMID- 24311186
TI  - Identification and bioassay of macrocyclic lactone sex pheromone of the halictine
      beeLasioglossum zephyrum.
AB  - The macrocyclic lactones found in the Dufour's gland of the halictine
      beeLasioglossum zephyrum are female sex pheromones. Octadecanolide, eicosanolide,
      docosanolide, and tetracosanolide, as well as monounsaturated homologs of each,
      are components of the Dufour's gland secretion of this species. Furthermore, a
      series of odd-carbon-numbered saturated and unsaturated hydrocarbons and
      isopentenyl docosanoate occur in extracts of the Dufour's gland and of whole
      females. Two different mixtures of all four synthetic lactones, and additionally
      a treatment consisting of the natural extract, elicit higher response levels than
      two of the lactones separately or either of the controls. 

PMID- 24311187
TI  - Practice patterns in the perioperative treatment of patients undergoing
      septorhinoplasty: a survey of facial plastic surgeons.
AB  - IMPORTANCE The common practices used in the perioperative care of patients
      undergoing septorhinoplasty are diverse and controversial. A consensus statement
      on the preferred clinical pathway in the perioperative treatment of patients
      undergoing septorhinoplasty has yet to be approached formally. OBJECTIVES To
      investigate the perioperative treatment of patients undergoing septorhinoplasty
      and to identify common practice patterns based on the preferences of leading
      facial plastic surgeons. DESIGN, SETTING, AND PARTICIPANTS We distributed an
      online survey to members of the American Academy of Facial Plastic and
      Reconstructive Surgery. Specifically, fellowship directors and academic contact
      members were anonymously polled and stratified by the number of
      septorhinoplasties performed annually. MAIN OUTCOME AND MEASURE A cohesive
      clinical guide to perioperative treatment after rhinoplasty. RESULTS Of the 92
      members surveyed, 67 (73%) successfully completed the survey. The distribution of
      respondents included 43 academicians (64%) and 24 physicians in private practice
      (36%). Twenty-eight surgeons (42%) performed fewer than 50 rhinoplasties a year
      and 39 (58%), more than 50, representing 3510 to 4549 septorhinoplasties in total
      among respondents. Forty-four surgeons (66%) refrained from using any packing,
      and 41 (61%) used intranasal splints, with polymeric silicone splints the most
      popular of these (n = 24 [59%]). Sixty-six surgeons (99%) used external nasal
      splints, including 49 (74%) who used a thermoplastic splint and 49 (74%) who left
      the external nasal splint in place for 7 days or longer. The most common
      postoperative interventions to reduce edema and ecchymosis were elevation of the
      head of bed by 62 (93%), ice packs by 50 (75%), and Arnica montana by 33 (49%).
      Only 12 surgeons (18%) used postoperative corticosteroids to reduce edema. Fifty
      six respondents (84%) prohibited participation in contact sports until at least 6
      weeks after surgery. CONCLUSIONS AND RELEVANCE Perioperative care and practices
      after nasal surgery vary among the most highly trained and leading rhinoplasty
      surgeons. No published communication or consensus on perioperative practices has
      been disseminated in this setting. Given the results from those surgeons
      performing the most rhinoplasties in our field, some surgeons may choose to vary
      their practices to coincide with those of experienced surgeons. These guidelines
      could facilitate future studies of patient outcomes.

PMID- 24311188
TI  - What parents want from doctors in end-of-life decision-making for children.
AB  - OBJECTIVE: End-of-life decision-making is difficult for everyone involved, as
      many studies have shown. Within this complexity, there has been little
      information on how parents see the role of doctors in end-of-life decision-making
      for children. This study aimed to examine parents' views and experiences of end
      of-life decision-making. DESIGN: A qualitative method with a semistructured
      interview design was used. SETTING: Parent participants were living in the
      community. PARTICIPANTS: Twenty-five bereaved parents. MAIN OUTCOMES: Parents
      reported varying roles taken by doctors: being the provider of information
      without opinion; giving information and advice as to the decision that should be
      taken; and seemingly being the decision maker for the child. The majority of
      parents found their child's doctor enabled them to be the ultimate decision maker
      for their child, which was what they very clearly wanted to be, and consequently
      enabled them to exercise their parental autonomy. Parents found it problematic
      when doctors took over decision-making. A less frequently reported, yet
      significant role for doctors was to affirm decisions after they had been made by
      parents. Other important aspects of the doctor's role were to provide follow-up
      support and referral. CONCLUSIONS: Understanding the role that doctors take in
      end-of-life decisions, and the subsequent impact of that role from the
      perspective of parents can form the basis of better informed clinical practice.

PMID- 24311189
TI  - 'Oral injury in child abuse'.

PMID- 24311190
TI  - "Proving that i am improving" where are we going?

PMID- 24311191
TI  - In vivo imaging of T cells loaded with gold nanoparticles: a pilot study.
AB  - PURPOSE: Malignant tumours develop strategies to avoid immune recognition and
      elimination by T cells, even in individuals with a fully functioning immune
      system. To explore the treatment approach of adoptive immunotherapy, we exploited
      T cells loaded with radiolabelled gold nanoparticles (AuNPs) to track T cells in
      vivo. MATERIALS AND METHODS: Surface-modified AuNPs were radiolabelled with
      (111)In or (64)Cu. They were then transferred into T cells via electroporation.
      To evaluate the effectiveness of this process, T cells loaded with (111)In
      radiolabelled AuNPs were injected directly into the right lung of nude mice for
      in vivo imaging by micro-SPECT/CT. T cells loaded with (64)Cu-radiolabelled AuNPs
      were then injected into the tail vein of nude mice and imaged by micro-PET/CT.
      RESULTS: High uptake signals were observed in the right lung following the direct
      injection of T cells containing (111)In-labelled AuNPs. Imaging showed a marked
      difference in the dynamic biodistribution of T cells containing (64)Cu-labelled
      AuNPs when compared with (64)Cu-labelled AuNPs alone. CONCLUSIONS: This study
      demonstrated the feasibility of the in vivo imaging of T cells loaded with
      radiolabelled AuNPs.

PMID- 24311193
TI  - Letter from Ralph J Cicerone regarding Edward Calabrese's paper published online
      first on August 4th: "how the US national academy of sciences misled the world
      community on cancer risk assessment: new findings challenge historical
      foundations of the linear dose response." [DOI 10.1007/s00204-013-1105-6, Review
      Article].

PMID- 24311192
TI  - Radioprotective effect of calcium channel blockers against late rectal bleeding
      in prostate cancer.
AB  - OBJECTIVE: This study was done to assess the impact of clinical factors and in
      particular the use of drugs for concomitant illnesses on late radiation-induced
      rectal bleeding in patients with prostate cancer. MATERIALS AND METHODS: Patients
      with histologically proven prostate adenocarcinoma treated with radical
      radiotherapy and followed up for at least 6 months were selected. The correlation
      between late rectal bleeding and a number of factors was investigated by
      univariate and multivariate analysis. RESULTS: A total of 278 patients who
      underwent radiotherapy at our institution between October 2002 and May 2011 were
      selected. At univariate analysis, delivery of radiation doses higher than 70 Gy
      and use of angiotensin-converting enzyme inhibitors were associated with a higher
      incidence of rectal bleeding. Conversely, patients who used calcium channel
      blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5
      %, p = 0.043). At multivariate analysis, use of calcium channel blockers was
      found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96).
      Delivery of higher radiation doses was associated with an increased risk of
      rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). CONCLUSIONS: Use of
      calcium channel blockers during and after radiotherapy treatment might have a
      protective effect against late rectal bleeding. If these results are reconfirmed
      by larger clinical series, calcium channel blockers may be tested as
      radioprotector agents in clinical trials.

PMID- 24311194
TI  - Changing interpretation of chromosomal microarray over time in a community cohort
      with intellectual disability.
AB  - Chromosomal microarray (CMA) is the first-line diagnostic test for individuals
      with intellectual disability, autism, or multiple congenital anomalies, with a 10
      20% diagnostic yield. An ongoing challenge for the clinician and laboratory
      scientist is the interpretation of variants of uncertain significance (VOUS)
      usually rare, unreported genetic variants. Laboratories differ in their threshold
      for reporting VOUS, and clinical practice varies in how this information is
      conveyed to the family and what follow-up is arranged. Workflows, websites, and
      databases are constantly being updated to aid the interpretation of VOUS. There
      is a growing literature reporting new microdeletion and duplication syndromes,
      susceptibility, and modifier copy number variants (CNVs). Diagnostic methods are
      also evolving with new array platforms and genome builds. In 2010, high
      resolution arrays (Affymetrix 2.7 M Oligo and SNP, 50 kB resolution) were
      performed on a community cohort of 67 individuals with intellectual disability of
      unknown aetiology. Three hundred and one CNVs were detected and analyzed using
      contemporary resources and a simple scoring system. Thirteen (19%) of the arrays
      were assessed as potentially pathogenic, 4 (6%) as benign and 50 (75%) of
      uncertain clinical significance. The CNV data were re-analyzed in 2012 using the
      contemporary interpretative resources. There was a statistically significant
      difference in the assessment of individual CNVs (P < 0.0001). An additional eight
      patients were reassessed as having a potentially pathogenic array (n = 21, 31%)
      and several additional susceptibility or modifier CNVs were identified. This
      study highlights the complexity involved in the interpretation of CMA and
      uniquely demonstrates how, even on the same array platform, it can be subject to
      change over time.

PMID- 24311195
TI  - Cellular internalisation of an inositol phosphate visualised by using fluorescent
      InsP5.
AB  - When applied extracellularly, myo-inositol hexakisphosphate (InsP6 ) and myo
      inositol pentakisphosphate (InsP5 ) can inhibit the growth and proliferation of
      tumour cells. There is debate about whether these effects result from
      interactions of InsP6 and InsP5 with intracellular or extracellular targets. We
      synthesised FAM-InsP5 , a fluorescent conjugate of InsP5 that allows direct
      visualisation of its interaction with cells. FAM-InsP5 was internalised by H1229
      tumour cells, a finding that supports earlier reports that externally applied
      inositol phosphates can-perhaps surprisingly-enter into cells. Close examination
      of the process of FAM-InsP5 uptake suggests a mechanism of non-receptor-mediated
      endocytosis, which is blocked at 4  degrees C and probably involves interaction
      of the ligand with the glycocalyx. However, our results are difficult to
      reconcile with antiproliferative mechanisms that require direct interactions of
      externally applied InsP5 or InsP6 with cytosolic proteins, because internalised
      FAM-InsP5 appears in lysosomes and apparently does not enter the cytoplasm.
      Studies using FAM-InsP5 are less difficult and time-consuming than experiments
      using InsP5 or InsP6 , a factor that allowed us to analyse cellular uptake across
      a range of human cell types, identifying strong cell-specific differences.

PMID- 24311196
TI  - Mindfulness based cognitive therapy may improve emotional processing in bipolar
      disorder: pilot ERP and HRV study.
AB  - Emotional processing in bipolar disorder (BD) is impaired. We aimed to measure
      the effects of mindfulness based cognitive-behavioral therapy (MBCT) in BD on
      emotional processing, as measured by event related potentials (ERP) and by heart
      rate variability (HRV). ERP and HRV were recorded during the completion of a
      visual matching task, which included object matching, affect matching, and affect
      labeling. Individuals with BD (n = 12) were compared with controls (n = 9) to
      obtain baseline data prior to the individuals with BD undergoing an 8-week MBCT
      intervention. ERP and HRV recording was repeated after the MBCT intervention in
      BD. Participants with BD had exaggerated ERP N170 amplitude and increased HRV HF
      peak compared to controls, particularly during the affect matching condition.
      After an 8-week MBCT intervention, participants with BD showed attenuation of ERP
      N170 amplitude and reduced HRV HF peak. Our findings support findings from the
      literature emphasizing that emotional processing in BD is altered, and suggesting
      that MBCT may improve emotional processing in BD. 

PMID- 24311197
TI  - High-level ERBB2 gene amplification is associated with a particularly short time
      to-metastasis, but results in a high rate of complete response once trastuzumab
      based therapy is offered in the metastatic setting.
AB  - Despite patient selection based on ERBB2 overexpression, not all patients benefit
      from trastuzumab therapy. We have investigated whether a ERBB2 gene dosage effect
      might provoke increased biological aggressiveness and altered trastuzumab
      sensitivity. Absolute ERBB2 copy numbers ("CN") and ERBB2/centromer 17 ratios
      ("R") were measured by FISH analysis in tumors of 127 patients receiving
      trastuzumab-based treatment for Her-2/neu overexpressing metastatic breast
      cancer. CN and R were both significantly associated with shorter time to first
      metastasis (TTM) (CN: OR: 1.099, 95% CI: 1.042-1.159; R: OR: 1.211, 95% CI: 1.080
      1.357) and longer PFS (CN: OR: 0.917, 95% CI: 0.867-0.969; R: OR: 0.840, 95% CI:
      0.743-0.949) in a continuous variable Cox's regression model. Tumors with
      ERBB2/centromer 17 ratios of <2.2 had a significantly shorter TTM (p = 0.002) and
      significantly longer PFS (p = 0.003) than tumors with low-level (R: 2.2-6) and
      high-level amplification (R: >6). Interestingly, when ERBB2 copy numbers were
      analyzed, a significantly shorter TTM (p = 0.001) and longer PFS (p = 0.026) were
      observed in the group with high-level amplified CN (CN: >13), while no difference
      was observed between non- and low-level amplified CN. R, but not CN, was an
      independent predictor of complete (CR; OR: 1.685; 95% CI: 1.122-2.532) and
      partial (PR; OR: 1.704; 95% CI: 1.136-2.556) response in logistic regression
      analysis. CR (p = 0.016) rates were significantly higher in the high-level
      amplification group (R > 6), but no difference existed in response rates between
      non- and low-level amplified tumors in Chi-square tests. High-level ERBB2
      amplification is associated with shorter TTM, but improved response to
      trastuzumab in metastatic breast cancer.

PMID- 24311198
TI  - Rapid and sensitive detection of lower respiratory tract infections by stuffer
      free multiplex ligation-dependent probe amplification.
AB  - Lower respiratory tract infection is one of the most common infectious diseases.
      However, conventional methods for detecting infectious pathogens are time
      consuming, and generally have a limited impact on early therapeutic decisions. We
      previously reported a rapid and sensitive method for detecting such pathogens
      using stuffer-free multiplex ligation-dependent probe amplification coupled with
      high-resolution CE-SSCP. In this study, we report an application of this method
      to the detection of respiratory pathogens. As originally configured, this method
      was capable of simultaneously detecting seven bacterial species responsible for
      lower respiratory tract infections, but its detection limit and assay time were
      insufficient to provide useful information for early therapeutic decisions. To
      improve sensitivity and shorten assay time, we added a target-specific
      preamplification step, improving the detection limit from 50 pg of genomic DNA to
      500 fg. We further decreased time requirements by optimizing the hybridization
      step, enabling the entire assay to be completed within 7 h while maintaining the
      same detection limit. Taken together, these improvements enable the rapid
      detection of infectious doses of pathogens (i.e. a few dozen cells), establishing
      the strong potential of the refined method, particularly for aiding early
      treatment decisions. 

PMID- 24311199
TI  - Multivariate genetic analyses in heterogeneous populations.
AB  - Martin and Eaves (Heredity 38(1):79-95, 1977) proposed a multivariate model for
      twin and family data in order to investigate potential differences in the genetic
      and environmental architecture of multivariate phenotypes. The general form of
      the model is the independent pathway model, which differentiates between genetic
      and environmental influences at the item level, and therefore permits the
      decomposition to differ across items. A restricted version is the common pathway
      model, where the decomposition takes place at the factor level. The paper has
      spurred numerous studies, and evidence for differences in genetic and
      environmental architecture has been established for personality and several other
      psychiatric phenotypes by showing a better fit of the independent pathway model
      compared to the common pathway model. We show that genome-wide association
      studies (GWAS) that use an aggregate score computed from multiple questionnaire
      items as a univariate phenotype implicitly assume a similar structure as the
      common pathway model. It has been shown that in case of a differential genetic
      and environmental architecture, multivariate GWAS methods can outperform the
      univariate GWAS approach. However, current multivariate methods rely on the
      assumptions of phenotypic and genetic homogeneity, that is, item responses are
      assumed to have the same means and covariances, and genetic effects are assumed
      to be the same for all subjects. We describe a distance-based regression
      technique that is designed to account for subgroups in the population, and that
      therefore can account for differential genetic effects. A first evaluation with
      simulated data shows a substantial increase of power compared to univariate GWAS.

PMID- 24311200
TI  - Genetic and environmental influences on depressive symptoms in Chinese
      adolescents.
AB  - Adolescent depression is common and has become a major public health concern in
      China, yet little research has examined the etiology of depression in Chinese
      adolescents. In the present study, genetic and environmental influences on
      Chinese adolescent depressive symptoms were investigated in 1,181 twin pairs
      residing in Beijing, China (ages 11-19 years). Child- and parent-versions of the
      children's depression inventory were used to measure adolescents' depressive
      symptoms. For self-reports, genetic factors, shared environmental factors, and
      non-shared environmental factors accounted for 50, 5, and 45 % of the variation
      in depressive symptoms, respectively; for parent-reports, genetic factors, shared
      environmental factors, and non-shared environmental factors accounted for 51, 18,
      and 31 % of the variation, respectively. These estimates are generally consistent
      with previous findings in Western adolescents, supporting the cross-cultural
      generalizability of etiological model of adolescent depression. Neither
      qualitative nor quantitative sex differences were found in the etiological model.
      Future studies are needed to investigate how genes and environments work together
      (gene-environment interaction, gene-environment correlation) to influence
      depression in Chinese adolescents.

PMID- 24311201
TI  - Economic burden and disparities in healthcare resource use among adult patients
      with cardiac arrhythmia.
AB  - BACKGROUND: As of 2012, approximately 4.3 million Americans experience some form
      of cardiac arrhythmia (CA). Assessment of economic burden and healthcare resource
      use on the overall CA population is limited. OBJECTIVES: To assess healthcare
      expenditure and disparities in healthcare resource use in patients with all forms
      of CA in the US. METHODS: Data from the Medical Expenditure Panel Survey were
      analyzed between 2004 and 2009. Patients aged>=18 years with any form of CA
      (identified via International Classification of Disorders Ninth Revision,
      Clinical Modification [ICD-9-CM] codes) were included. Primary independent
      variables included age, gender, race/ethnicity, and pharmacotherapy use. Outcomes
      of interest included total annual healthcare and prescription expenditures
      (inflation adjusted to 2011), use of anti-arrhythmic agents associated with CA,
      and inpatient, outpatient, or emergency room visits. Generalized linear models
      were used to assess the disparities across patient subgroups related to the
      outcomes. RESULTS: Annually, 5,750,440 individuals experienced CA in the US.
      Total direct annual healthcare cost of CA summed up to $US67.4 billion. Non
      Hispanic whites and older adult patients had higher expenditures and use of
      healthcare resources (p<0.05). Female patients had significantly higher
      prescribed medication expenditures and a lower proportion of inpatient and
      emergency room visits related to arrhythmia (p<0.05). Patients taking anti
      arrhythmic agents had significantly higher expenditure and a lower proportion of
      emergency department visits related to arrhythmia (p<0.05). CONCLUSIONS: CA
      represents a substantial economic burden in the US, especially for the older
      adult population. Patients other than non-Hispanic whites may not have adequate
      access to healthcare treatment for arrhythmia.

PMID- 24311202
TI  - Cytogenetics of a factor for syncyte formation and male sterility in Pennisetum
      americanum.
AB  - Male sterility in Pennisetum americanum (L.) Leeke, inbred line IP 482, was found
      to be inherited as a monofactorial recessive phenotype. Homozygosity for the gene
      designated ms 2, produced in addition to pollen abortion, plasmodial tapetum,
      plasmodial pollen mother cells, delayed and asynchronous meiotic development,
      desynapsis and blockage of meiosis. Plasmodial PMCs resulted from the fusion of
      PMCs at pachytene. 

PMID- 24311203
TI  - Participation of the intracellular enzymes in the control of the mutation process
      : III. Influence of the inhibition of repair and replication on gamma-ray induced
      chromosomal aberrations in barley.
AB  - The influence of repair and replication on the frequency of spontaneous
      chromosome aberrations and of those induced by gamma-irradiation is
      reported.Using the technique of labelling DNA with radioactive (3)H-thymidine and
      measuring the radioactivity of DNA isolated from embryos, the time of initiation
      and the duration of DNA synthesis in barley seeds was studied after the soaking
      of the seeds had begun. The average duration of each phase of the first DNA
      synthesis cycle in soaking barley seeds was found to be as follows: pre-DNA
      synthesis stage, 10-11 hrs; DNA synthesis stage, 8 hrs. After gamma-irradiation,
      the intensity of DNA synthesis decreased and the beginning of DNA synthesis was
      delayed.It was found that the inhibition of repair by caffeine led to an increase
      in the frequency of both spontaneous and induced chromosome aberrations. Caffeine
      enhanced several times the frequency of chromosome and chromatid aberrations at
      the time of the maximal activity of repair enzymes. During DNA replication,
      caffeine had a lower effect on the realization of premutational lesions.An
      inhibitor of DNA replication - hydroxyurea - had no influence on the frequency of
      spontaneous chromosome aberrations during the replication period, whereas after
      gamma-irradiation, hydroxyurea enhanced the frequency of aberrations mainly at
      the stage of DNA replication.The relatively small mutagenic action of both agents
      (caffeine and hydroxyurea) was observed during all stages of the cell cycle of
      germinating barley seeds. 

PMID- 24311204
TI  - Theory of nucleus breeding schemes with overlapping generations.
AB  - Explicit methods are derived for estimating steady-state genetic responses and
      genetic differences between nucleus and base progeny crops in open nucleus
      breeding schemes which utilize genetic differences between progeny groups with
      parents of different ages or between age groups. Explicit methods are also given
      for estimating proportions which should be selected from the different nucleus
      and base selection groups so as to maximise genetic responses under each of a
      range of selection methods. Some basic differences between selection programmes
      utilizing genetic differences between progeny groups with parents of different
      ages and those utilizing genetic differences between age groups in nucleus
      breeding schemes are summarized. 

PMID- 24311205
TI  - Possible biases in heritability estimates from intraclass correlation.
AB  - There is an inherent bias in intraclass correlations since the expectation of a
      ratio does not equal the ratio of expectations. A simple accurate approximation
      for this bias is derived, and it is found that the inherent bias is usually
      negligible. Selection of sires is known to bias half-sib heritability estimates,
      and appropriate formulae are given and discussed. 

PMID- 24311206
TI  - Genetics of seed-coat colour in Citrullus lanatus (Thunb.) Mansf.
AB  - Intervarietal crosses in watermelon, Citrullus lanatus (Thunb.) Mansf., involving
      six parents with black (J18-1 and J 75), brown (J56-1 and N.H. Midget), red
      (Bykovski-199) or light cream (Red Nectar) seed-coat colour were made. Parents,
      F1, F2 and backcross populations were evaluated for their phenotypic expressions
      with regard to the seed-coat colours involved. Black colour was monogenically
      dominant over brown light cream and red colour of seed-coat separately or
      independently. Red colour was dominant over light cream colour of seed-coat by a
      single pair of genes. The light cream colour was recessive to the brown seed-coat
      colour of watermelon where a single pair of genes was involved. 

PMID- 24311207
TI  - The cytogenetic structure of Vicia sativa aggregate.
AB  - The cytogenetic structure of Vicia sativa aneuploid series was assessed by
      examination of the chromosome pairing in hybrids between types having 2n = 10, 2n
      = 12 and 2n = 14. Two different karyotypes were distinguished at both the 2n = 10
      and 2n = 12 levels. Chromosome pairing in hybrids involved two 2n = 10
      karyotypes, indicating that the parental lines differed by two translocations. A
      similar indication was obtained for the two 2n = 12 karyotypes employed. The
      meiotic behavior of the 2n = 10 x 2n = 12 hybrids indicated that the parental
      lines differed by up to three translocations, some of which involved unequal
      chromosome segments. It has been proposed that the 2n = 10 types were developed
      from the 2n = 12 via centric or tandem fusion and additional rearrangements
      further accelerated chromosome repatterning at the two 2n levels. Hybrids between
      the 2n = 14 V. sativa and the former 2n types had very irregular chromosome
      pairing and were highly sterile. It has been proposed that the 2n = 14 type is a
      relatively new evolvement in V. sativa because of its shorter complement in
      comparison with the other karyotypes. The subterraneous pods of the 2n = 14 type,
      a characteristic which is absent in other V. sativa types and in the entire genus
      Vicia, also supports an advanced, phylogenetic position. The 2n = 14 type
      probably arose from n = 7 gametes produced by the 2n= 12 x 2n = 10 hybrid and the
      establishment of the row 2n = 14 type was acquired through conspicuous chromosome
      deletions. In spite of its remarkable chromosomal variation, V. sativa can still
      be considered, for breeding purposes, as being one gene pool. The wild forms of
      V. sativa can thus be valuable sources for improving the cultivated vetch. 

PMID- 24311208
TI  - Direct pollination of Zea mays ovules in vitro with Z. mays, Z. mexicana and
      Sorghum bicolor pollen.
AB  - Sorghum (Sorghum bicolor) pollen tubes penetrated and grew in corn (Zea mays)
      styles. The limited length of the sorghum pollen tubes (3-5 mm) and the absence
      of stigmatic hairs on the basal (5-10 mm) section of the corn styles prevented
      effective pollination in vivo and in vitro. Normal fertilisation occurred after
      in vitro pollination of exposed corn ovules with either corn or teosinte (Zea
      mexicana) pollen. Six per cent of corn ovules pollinated directly with sorghum
      pollen responded by rapid, massive growth of nucellar tissue. 

PMID- 24311209
TI  - Fluorescence detected magnetic resonance (FDMR) of green sulfur photosynthetic
      bacteria Chlorobium sp.
AB  - Fluorescence Detected Magnetic Resonance (FDMR) spectra have been measured for
      whole cells and isolated chlorosomal fractions for the green photosyntheic
      bacteria Chlorobium phaeobacteroides (containing bacteriochlorophyll e, and
      isorenieratene as major carotenoid) and Chlorobium limicola (containing
      bacteriochlorophyll c, and chlorobactene as major carotenoid). The observed
      transition at 237 MHz (identical in both bacteria) and > 1100 MHz can be
      assigned, by analogy with published data on other carotenoids, to the 2E and D +
      E transitions, respectively, of Chlorobium carotenoids. Their zero field
      splitting (ZFS) parameters are estimated to be: |D|=0.0332 cm(-1) and |E|=0.0039
      cm(-1) (chlorobactene), and |D|=0.0355 cm(-1) and |E|=0.0039 cm(-1)
      (isorenieratene). In the intermediate frequency range 300-1000 MHz the observed
      transitions can be assigned to chlorosomal bacteriochlorophylls c and e, and to
      bacteriochlorophyll a located in the chlorosome envelope and water-soluble
      protein. The bacteriochlorophyll e triplet state measured in 750 nm fluorescence
      (aggregated chlorosomal BChl e) is characterised by the ZFS parameters:
      |D|=0.0251 cm(-1) and |E|=0.0050 cm(-1). 

PMID- 24311210
TI  - Molecular topology of the Photosystem II chlorophyll a binding protein, CP 43:
      Topology of a thylakoid membrane protein.
AB  - We have used antibodies generated against synthetic peptides to determine the
      topology of the 43 kD chlorophyll a binding protein (CP 43) of Photosystem II.
      Based on the pattern of proteolytic fragments detected (on western blots) by
      peptide specific antibodies, a six transmembrane span topological model, with the
      amino and carboxyl termini located on the stromal membrane surface, is predicted.
      This structure is similar to that predicted for CP 47, a PS II chlorophyll a
      binding protein (Bricker T (1990) Photosynth Res 24: 1-13). The model is
      discussed in reference to the possible location of chlorophyll binding sites. 

PMID- 24311211
TI  - Resolution of low-energy chlorophylls in Photosystem I of Synechocystis sp. PCC
      6803 at 77 and 295 K through fluorescence excitation anisotropy.
AB  - Fluorescence excitation spectra of highly anisotropic emission from Photosystem I
      (PS I) were measured at 295 and 77 K on a PS II-less mutant of the cyanobacterium
      Synechocystis sp. PCC 6803 (S. 6803). When PS I was excited with light at
      wavelengths greater than 715 nm, fluorescence observed at 745 nm was highly
      polarized with anisotropies of 0.32 and 0.20 at 77 and 295 K, respectively. Upon
      excitation at shorter wavelengths, the 745-nm fluorescence had low anisotropy.
      The highly anisotropic emission observed at both 77 and 295 K is interpreted as
      evidence for low-energy chlorophylls (Chls) in cyanobacteria at room temperature.
      This indicates that low-energy Chls, defined as Chls with first excited singlet
      state energy levels below or near that of the reaction center, P700, are not
      artifacts of low-temperature measurements.If the low-energy Chls are a distinct
      subset of Chls and a simple two-pool model describes the excitation transfer
      network adequately, one can take advantage of the low-energy Chls' high
      anisotropy to approximate their fluorescence excitation spectra. Maxima at 703
      and 708 nm were calculated from 295 and 77 K data, respectively. Upper limits for
      the number of low-energy Chls per P700 in PS I from S. 6803 were calculated to be
      8 (295 K) and 11 (77 K). 

PMID- 24311212
TI  - Pigment orientation changes accompanying the light state transition in
      Synechococcus sp. PCC 6301.
AB  - Low temperature (77 K) linear dichroism spectroscopy was used to characterize
      pigment orientation changes accompanying the light state transition in the
      cyanobacterium, Synechococcus sp. PCC 6301 and those accompanying chromatic
      acclimation in Porphyridium cruentum in samples stabilized by glutaraldehyde
      fixation. In light state 2 compared to light state 1 intact cells of
      Synechococcus showed an increased alignment of allophycocyanin parallel to the
      cells' long axis whereas the phycobilisomethylakoid membrane fragments exhibited
      an increased allophycocyanin alignment parallel to the membrane plane. The
      phycobilisome-thylakoid membrane fragments showed less alignment of a short wave
      length chlorophyll a (Chl a) Qy transition dipole parallel to the membrane plane
      in state 2 relative to state 1.To aid identification of the observed Chl a
      orientation changes in Synechococcus, linear dichroism spectra were obtained from
      phycobilisome-thylakoid membrane fragments isolated from red light-grown
      (increased number of PS II centres) and green light-grown (increased number of PS
      I centres) cells of the red alga Porphyridium cruentum. An increased contribution
      of short wavelength Chl a Qy transition dipoles parallel to the long axis of the
      membrane plane was directly correlated with increased levels of PS II centres in
      red light-grown P. cruentum.Our results indicate that the transition to state 2
      in cyanobacteria is accompanied by an increase in the orientation of
      allophycocyanin and a decrease in the orientation of Chl a associated with PS II
      with respect to the thylakoid membrane plane. 

PMID- 24311213
TI  - The use of photothermal radiometry in assessing leaf photosynthesis: II.
      Correlation of energy storage to Photosystem II fluorescence parameters.
AB  - Following the first part of this work (Malkin et al. (1991) Photosynth Res 29: 87
      96), where modulated photothermal radiometry (PTR) was used to measure energy
      storage (ES) in intact leaves as a function of P700 redox state, we report here
      on simultaneous ES and fluorescence measurements, which characterize the state of
      PS II. PTR monitors the conversion of modulated light into heat by measuring the
      modulated infra-red radiation emitted from the sample. The ratio [PTR+-PTR
      ]/PTR+, where PTR indicates the PTR signal and the subscripts +,- indicate the
      presence or absence of saturating background light, is used to quantitate ES. We
      searched carefully for the right conditions where the background light does not
      introduce a significant rise in the leaf temperature, which influences the PTR
      signal as such, otherwise the above ratio deviates from the true ES. Under such
      conditions, ES and the fluorescence parameters, F (momentary fluorescence level)
      Fm' (fluorescence of fully reduced PS II reaction centers) were measured during
      the induction phase of photosynthesis and in the steady state. ES and the
      parameter gamma=(Fm'-F)/Fm', considered by Genty et al. ((1989) Biochim Biophys
      Acta 990: 87-92) to reflect the yield of PS II, had similar kinetics during the
      induction phase. Both reached a final maximum plateau after about 4-5 min. of
      illumination. In different experiments, where the measuring light intensities
      varied, gamma was approximately linearly related to ES. This linear relationship
      was found in the same way also in steady-state measurements, where these
      parameters varied by using different background light intensities. Extrapolation
      to an ES value of zero indicates a finite non-zero value of gamma. A possible
      explanation for this may be found in the existence an electron transport cycle
      around PS II which does not store energy in the range corresponding to the
      modulation frequency used (ca. 3.6 Hz). 

PMID- 24311214
TI  - Spectroscopic characterization of reaction centers of the (M)Y210W mutant of the
      photosynthetic bacterium Rhodobacter sphaeroides.
AB  - The tyrosine-(M)210 of the reaction center of Rhodobacter sphaeroides 2.4.1 has
      been changed to a tryptophan using site-directed mutagenesis. The reaction center
      of this mutant has been characterized by low-temperature absorption and
      fluorescence spectroscopy, time-resolved sub-picosecond spectroscopy, and
      magnetic resonance spectroscopy. The charge separation process showed bi
      exponential kinetics at room temperature, with a main time constant of 36 ps and
      an additional fast time constant of 5.1 ps. Temperature dependent fluorescence
      measurements predict that the lifetime of P(*) becomes 4-5 times slower at
      cryogenic temperatures. From EPR and absorbance-detected magnetic resonance
      (ADMR, LD-ADMR) we conclude that the dimeric structure of P is not significantly
      changed upon mutation. In contrast, the interaction of the accessory
      bacteriochlorophyll BA with its environment appears to be altered, possibly
      because of a change in its position. 

PMID- 24311215
TI  - Model studies of chlorophyll fluorescence reabsorption at chloroplast level under
      different exciting conditions.
AB  - A theoretical model is presented describing the distortion of chlorophyll
      fluorescence spectra of a chloroplast or a group of chloroplasts by the effect of
      fluorescence reabsorption. Model calculations using the experimental data show
      that the primary reabsorption effect occurs already within one chloroplast and
      the spectral distortion depends significantly on the excitation regime of the
      chloroplast. A theoretical dependence of the distortion function, defined as a
      change in the F(685)/F(735) fluorescence band ratio, on the mean chlorophyll
      concentration in a chloroplast is predicted for different light excitation
      regimes. The distortion of measured chlorophyll fluorescence spectra at 77 K of
      chloroplast suspension adsorbed on filter papers of two strongly different
      diffusive reflectivities and at different mean chlorophyll concentrations are
      discussed with the help of the presented theory. 

PMID- 24311216
TI  - Photoinhibition of photosynthesis in chilled potato leaves is not correlated with
      a loss of Photosystem-II activity : Preferential inactivation of Photosystem I.
AB  - When 23  degrees C-grown potato leaves (Solanum tuberosum L.) were irradiated at
      23  degrees C with a strong white light, photosynthetic electron transport and
      Photosystem-II (PS II) activity were inhibited in parallel. When the light
      treatment was given at a low temperature of 3  degrees C, the photoinhibition of
      photosynthesis was considerably enhanced, as expected. Surprisingly, no such
      stimulation of photoinhibition was observed with respect to the PS II function. A
      detailed functional analysis of the photosynthetic apparatus, using in-vivo
      fluorescence, absorbance, oxygen and photoacoustic measurements, and artificial
      electron donors/acceptors, showed a pronounced alteration of PS I activity during
      light stress at low temperature. More precisely, it was observed that both the
      pool of photooxidizeable reaction center pigment (P700) of PS I and the
      efficiency of PS I to oxidize P700 were dramatically reduced. Loss of P700
      activity was shown to be essentially dependent on atmospheric O2 and to require a
      continued flow of electrons from PS II, suggesting the involvement of the
      superoxide anion radical which is produced by the interaction of O2 and the
      photosynthetic electron-transfer chain through the Mehler reaction. Mass
      spectrometric measurements of O2 exchange by potato leaves under strong
      illumination did not reveal, however, any stimulation of the Mehler reaction at
      low temperature, thus leading to the conclusion that O2 toxicity mainly resulted
      from a chilling-induced inhibition of the scavenging system for O2-radicals.
      Support for this interpretation was provided by the light response of potato
      leaves infiltrated with an inhibitor (diethyldithiocarbamate) of the
      chloroplastic Cu-Zn superoxide dismutase. It was indeed possible to simulate the
      differential inhibition of the PS II photochemical activity and the linear
      electron transport observed during light stress at low temperature by
      illuminating at 23  degrees C diethyldithiocarbamate-poisoned leaves. The
      experimental data presented here suggests that (i) the previously reported
      resistance of PS I to photoinhibition damage in-vivo is not an intrinsic property
      of PS I but results from efficient protective systems against O2 toxicity, (ii)
      PS I is photoinhibited in chilled potato leaf due to the inactivation of this PS
      I defence system and (iii) PS I is more sensitive to superoxide anion radicals
      than PS II. 

PMID- 24311217
TI  - On the relationship between chlorophyll fluorescence quenching and the quantum
      yield of electron transport in isolated thylakoids.
AB  - The relationship between the empirical fluorescence index DeltaF/Fm' and the
      quantum yield of linear electron flow, Phi(s), was investigated in isolated
      spinach thylakoids. Conditions were optimised for reliable determination of
      DeltaF/Fm' and Phi(s) with methyl viologen or ferricyanide as electron acceptors
      under coupled and uncoupled conditions. Ascorbate in combination with methyl
      viologen was found to stimulate light-induced O2-uptake which is not reflected in
      DeltaF/Fm' and interpreted to reflect superoxide reduction by ascorbate. In the
      absence of ascorbate, the plot of DeltaF/Fm' vs. Phi(s) was mostly linear, except
      for the range of high quantum yields, i.e. at rather low photon flux densities.
      With ferricyanide as acceptor, use of relatively low concentrations (0.1-0.3 mM)
      was essential for correct Fm'-determinations, particularly under uncoupled
      conditions. Under coupled and uncoupled conditions the same basic relationship
      between DeltaF/Fm' and Phi(s) was observed, irrespective of Phi(s) being
      decreased by increasing light intensity or by DCMU-addition. The plots obtained
      with methyl viologen and ferricyanide as acceptors were almost identical and
      similar to corresponding plots reported previously by other researchers for
      intact leaves. It is concluded that the index DeltaF/Fm' can be used with
      isolated chloroplasts for characterisation of such types of electron flow which
      are difficult to assess otherwise, as e.g. O2 dependent flux. The origin of the
      'non-linear' part of the relationship is discussed. An involvement of 'inactive'
      PS II centers with separate units and inefficient QA-QB electron transfer is
      considered likely. 

PMID- 24311218
TI  - State adaptations in the cyanobacterium Synechcoccus 6301 (PCC): Dependence on
      light intensity or spectral composition?
AB  - A profile of high light to intense self-shading conditions was constructed using
      a white light source and cultures of the cyanobacterium Synechococcus 6301; this
      profile approximates to a natural self-shading gradient of decreasing light
      intensity and PS II/PS I excitation ratio. Samples of S.6301 were placed along
      this profile and allowed to state adapt. To separate the effects of light
      intensity and wavelength on state adaptation, samples were also placed in a shade
      profile produced by a white light source and neutral density filters. After
      adaptation, samples were fixed in their resulting state by the addition of
      glutaraldehyde, and fluorescence measurements were made at 35 degrees  C or -160 
      degrees C. It is concluded: 1. Under conditions of deep shade (<5 MUmol m(-2)s(
      1) PAR) and weak shade (>200 MUmol m(-2)s(-1) PAR), cells adapt to a low PS II
      fluorescence state (state 2); in moderate shade (20-60 MUmol m(-2)s(-1)PAR) cells
      adapt to a high PS II fluorescence state (state 1). We suggest these findings
      provide evidence for the operation of different factors on the control of state
      adaptations in cyanobacteria; one set operates at low light and another at high
      light intensities. 2. Under conditions of self-shading, there is little evidence
      to support the contention that state adaptations in cyanobacteria are produced by
      wavelength-dependent changes in the PS II/PS I excitation ratio, instead, it
      appaers they are produced by changes in the intensity of incident irradiation. 3.
      The observed fluorescence changes do not appear to involve major changes in the
      phycobilisome sensitisation of PS II and PS I. Instead, it appears that these
      changes are effected by alterations in Phi(F) of PS II (i.e. changes in PS II
      excitation density caused by alterations in the rate constants controlling
      spillover to PS I, photochemistry, fluorescence emission or thermal deactivation.

PMID- 24311219
TI  - Selection of soybean plant leaves which yield mesophyll cell isolates with
      maximal rates of CO2 and NO inf2 (sup-) photoassimilation.
AB  - A problem often encountered when assaying mesophyll cell isolates prepared from
      mature soybean leaves, was that of poor reproducibility in rates of net (14)CO2
      photoassimilation and NO2 (-) photoreduction. It was known that soybean source
      leaves repeatedly displayed their most active net CO2 photoassimilation in the
      period from attainment of maximal leaf area to approximately two to five days
      subsequent to that point. Advantage was taken of the fact that when soybean
      leaflets of each leaf reach their maximal area they also have reached their
      maximal leaf length from base to tip. This facilitates a more rapid determination
      of the point in time in which leaflet areas had reached Amax. Soybean plants
      (Glycine max cv. Williams) were propagated in the growth chamber with a 12 h
      light-12 h dark cycle, 25deltaC, 65% RH, and 700 microeinsteins per meter squared
      per second. At 24 d post-emergence, the third leaf (numbered acropetally from the
      unifoliates) of each plant had just attained maximum leaflet areas (~110 cm(2))
      and lengths (~13 cm). For this study, leaf mesophyll cells were enzymatically
      isolated, using commercially prepared pectinase, from leaflet sets of leaves
      selected from each of the second, third, and fourth leaf positions. Maximal rates
      of net (14)CO2 photoassimilation (with 5 mM HCO3 (-)) for the second, third and
      fourth leaf (leaflet) isolates were, respectively, 27.0, 57.0, and 41.7 MUmol
      (14)CO2 assimilated per milligram chlorophyll per hour; simultaneously maximal
      rates of NO inf2 (sup-) photoreduction (1 mM NO inf2 (sup-) ) were, respectively,
      4.4, 8.1, and 0.0 MUmol NO inf2 (sup-) reduced per milligram chlorophyll per
      hour. These studies made it clear that in order repeatedly to attain reproducible
      maximal rates of leaf cell isolate net (14)CO2 photoassimilation and NO inf2 (sup
      ) photoreduction, it always was necessary to select the newest, fully expanded
      leaves (e.g. leaf number 3) for cell isolation. Leaves from several plants only
      were pooled if they were excised from identically the same node on each of the
      plants. 

PMID- 24311220
TI  - Waardenburg syndrome type 4: report of two new cases caused by SOX10 mutations in
      Spain.
AB  - Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a
      neurocristopathy characterized by the association of deafness, depigmentation and
      Hirschsprung disease. Three disease-causing genes have been identified so far for
      WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients,
      are inherited in autosomal dominant way. In addition, mutations in SOX10 are also
      responsible for an extended syndrome involving peripheral and central
      neurological phenotypes, referred to as PCWH (peripheral demyelinating
      neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome,
      Hirschsprung disease). Such mutations are mostly private, and a high intra- and
      inter-familial variability exists. In this report, we present a patient with WS4
      and a second with PCWH due to SOX10 mutations supporting again the genetic and
      phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family
      carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in
      distinct phenotypes along three different generations: hypopigmentation in the
      maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since
      mosaicism cannot explain the three different related-WS features observed in this
      family, we propose as the most plausible explanation the existence of additional
      molecular events, acting in an additive or multiplicative fashion, in genes or
      regulatory regions unidentified so far. On the other hand, the PCWH case was due
      to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel
      the mechanisms underlying the intrafamilial phenotypic variability observed in
      the families affected, and to identify new genes responsible for the still
      unsolved WS4 cases.

PMID- 24311221
TI  - What motivates patients and carers to participate in dementia research? Results
      from a series of focus groups in Scotland.

PMID- 24311222
TI  - Urinary incontinence in people with Alzheimer's disease.

PMID- 24311223
TI  - Instrumental activities of daily living in remitted late-life depression: a
      preliminary study.

PMID- 24311224
TI  - Urocortin 2 treatment is protective in excitotoxic retinal degeneration.
AB  - Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many
      physiological functions and it has widespread distribution. There are some data
      on the cytoprotective effects of Ucn 2, but less is known about its neuro- and
      retinoprotective actions. We have previously shown that Ucn 2 is protective in
      ischemia-induced retinal degeneration. The aim of the present study was to
      examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced
      retinal degeneration by routine histology and to investigate cell-type specific
      effects by immunohistochemistry. Rat pups received MSG applied on postnatal days
      1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were
      processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was
      determined for glial fibrillary acidic protein, vesicular glutamate transporter
      1, protein kinase Calpha, calbindin, parvalbumin and calretinin. Retinal tissue
      from animals treated with MSG showed severe degeneration compared to normal
      retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal
      structure both at histological and neurochemical levels: distinct inner retinal
      layers and rescued inner retinal cells (different types of amacrine and rod
      bipolar cells) could be observed. These findings support the neuroprotective
      function of Ucn 2 in MSG-induced retinal degeneration. 

PMID- 24311225
TI  - Effect of exercise intensity on cerebrospinal fluid interleukin-6 concentration
      during recovery from exhaustive exercise in rats.
AB  - The purpose of this study was to investigate the possible role of moderate and
      strenuous swimming training on plasma and cerebrospinal fluid (CSF) IL-6
      (interleukin-6) levels during recovery from exhaustive exercise in rats. Wistar
      rats were divided into three groups: sedentary control (C), moderately trained
      (MT) and strenuously trained (ST). MT rats underwent swimming exercise for one
      hour/day and 5 days/week for 8 weeks. Animals in the ST group began swimming with
      1 h/day and swimming duration was progressively increased by 30 min/wk, reaching
      2.5 h/day by week 4 and stayed constant for an additional 4 weeks. After all
      animals underwent an acute exhaustive swimming exercise, animals were divided
      into 3 groups, and decapitated immediately, 24 and 48 hours after exhaustion to
      obtain tissue samples. Muscle citrate synthase activity, plasma and CSF IL-6
      levels were determined. The citrate synthase activity was found to be higher in
      MT and ST groups compared to the C group. Although plasma IL-6 levels were found
      unaltered among all groups, the CSF IL-6 concentration was found to be increased
      24 hours after exhaustive exercise of the ST group. We conclude that exercise
      training intensity is an important factor determining cerebrospinal IL-6
      concentration after exhaustive exercise. 

PMID- 24311226
TI  - Oxidative stress in blood and testicle of rat following intraperitoneal
      administration of aluminum and indium.
AB  - Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects,
      oxidative stress being one of the possible mechanisms involved in their
      cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip)
      administration induced histological disorganization of testicular tissue. In the
      present research we aimed at investigating the effect of Al and In ip
      administration on systemic and testicular oxidative stress status. Studies were
      performed on Wistar rats ip injected with Al, In or physiological solution for
      two weeks. Our results showed that In significantly decreased the absolute weight
      of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON)
      activities showed that In induced a significant augmentation in the first
      parameter but no changes were observed in the second. Both Al and In caused
      oxidative stress in testicles by increasing malondialdehyde (MDA) and protein
      carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH)
      level were enhanced in the testicles. In the blood, while concentrations of MDA
      was not changed, those of GSH was significantly decreased in the Al and In
      groups. Our results indicated that Al and In cause oxidative stress both in blood
      and testicles but In has cytotoxic effect as well as negative impact on testicle
      weights. These findings could explain the testicular histological alterations
      previously described after In ip administration. 

PMID- 24311227
TI  - Hyperhomocysteinemia and hyperlipoproteinemia (a) in obese South Indian men: an
      indication for increased cardiovascular risk.
AB  - Obesity is a pathological condition which increases the risk for cardiovascular
      disease. The present study was designed to evaluate homocysteine, lipoprotein (a)
      [Lp(a)], apolipoprotein-B (apo-B), apolipoprotein-A-I (apo-A-I) and lipid indices
      and their association if any in obese South Indian men. Thirty obese men and
      thirty age-matched males with normal body weight (controls) were recruited in the
      study. Plasma homocysteine, Lp(a), lipid profile, apo-A-I and apo-B were
      estimated in all the subjects. Lipid indices such as lipid pentad index (LPI),
      lipid tetrad index (LTI), atherogenic index of plasma (AIP), non-high density
      lipoprotein (non-HDL)/high density lipoprotein (HDL) ratio and apo-B/apo-A-I
      ratio were calculated in all study subjects. Homocysteine, Lp(a), apo-B, apo
      B/apo-A-I ratio and lipid indices were significantly increased in obese men,
      compared to controls. Both homocysteine and Lp(a) were positively correlated with
      BMI, waist, hip circumference and apo-B and negatively correlated with apo-A-I.
      Also we found highly significant positive correlation between homocysteine and
      Lp(a) levels. The data from the present study concludes that non-conventional
      risk factors like homocysteine, Lp (a), apo-B/apo-A-I ratio, LTI, LPI, non
      HDL/HDL ratio and AIP were significantly elevated in obese Indian men, suggesting
      they are more prone to develop cardiovascular disease, than the age-matched men
      with normal body weight. 

PMID- 24311228
TI  - Response of end tidal CO2 pressure to impulse exercise.
AB  - The purpose of the present study was to examine how end tidal CO(2) pressure
      (PETCO(2)) is controlled in impulse exercise. After pre-exercise at 25 watts for
      5 min, impulse exercise for 10 sec with 200 watts followed by post exercise at 25
      watts was performed. Ventilation (VE) significantly increased until the end of
      impulse exercise and significantly re-increased after a sudden decrease. Heart
      rate (HR) significantly increased until the end of impulse exercise and then
      decreased to the pre-exercise level. PETCO(2) remained constant during impulse
      exercise. PETCO(2) significantly increased momentarily after impulse exercise and
      then significantly decreased to the pre-exercise level. PETCO(2) showed
      oscillation. The average peak frequency of power spectral density in PETCO(2)
      appeared at 0.0078 Hz. Cross correlations were obtained after impulse exercise.
      The peak cross correlations between VE and PETCO(2), HR and PETCO(2), and VE and
      HR were 0.834 with a time delay of -7 sec, 0.813 with a time delay of 7 sec and
      0.701 with a time delay of -15 sec, respectively. We demonstrated that PETCO(2)
      homeodynamics was interactively maintained by PETCO(2) itself, CO(2)
      transportation (product of cardiac output and mixed venous CO(2) content) into
      the lungs by heart pumping and CO(2) elimination by ventilation, and it
      oscillates as a result of their interactions.

PMID- 24311230
TI  - Identifying enantiomers in mixtures of chiral molecules with broadband microwave
      spectroscopy.
AB  - Chirality-sensitive broadband microwave spectroscopy was performed on mixtures of
      carvone enantiomers and conformers to distinguish enantiomers, measure
      enantiomeric excesses, and determine the absolute configurations of the
      enantiomers. This method uses microwave three-wave mixing and is inherently well
      suited to the analysis of mixtures-a unique advantage over other techniques. In
      contrast to conventional microwave spectroscopy, the phase of the received signal
      is also exploited. This phase depends upon the signs of the molecules' dipole
      moment components and is used to identify the excess enantiomer. The measured
      signal amplitude determines the size of the excess. The broadband capabilities of
      the spectrometer were used to simultaneously excite and measure two conformers of
      carvone, demonstrating the analysis of a sample with multiple chiral species.
      Employing quantum chemical calculations and the measured phases, the absolute
      configurations of the enantiomers are determined. 

PMID- 24311229
TI  - Functionalized tricyclic cytosine analogues provide nucleoside fluorophores with
      improved photophysical properties and a range of solvent sensitivities.
AB  - Tricyclic cytosines (tC and tC(O) frameworks) have emerged as a unique class of
      fluorescent nucleobase analogues that minimally perturb the structure of B-form
      DNA and that are not quenched in duplex nucleic acids. Systematic derivatization
      of these frameworks is a likely approach to improve on and diversify
      photophysical properties, but has not so far been examined. Synthetic methods
      were refined to improve on tolerance for electron-donating and electron
      withdrawing groups, resulting in a series of eight new, fluorescent cytidine
      analogues. Photophysical studies show that substitution of the framework results
      in a pattern of effects largely consistent across tC and tC(O) and provides
      nucleoside fluorophores that are brighter than either parent. Moreover, a range
      of solvent sensitivities is observed, offering promise that this family of probes
      can be extended to new applications that require reporting on the local
      environment. 

PMID- 24311233
TI  - Molecular pathology via IR and Raman spectral imaging.
AB  - During the last 15 years, vibrational spectroscopic methods have been developed
      that can be viewed as molecular pathology methods that depend on sampling the
      entire genome, proteome and metabolome of cells and tissues, rather than probing
      for the presence of selected markers. First, this review introduces the
      background and fundamentals of the spectroscopies underlying the new
      methodologies, namely infrared and Raman spectroscopy. Then, results are
      presented in the context of spectral histopathology of tissues for detection of
      metastases in lymph nodes, squamous cell carcinoma, adenocarcinomas, brain tumors
      and brain metastases. Results from spectral cytopathology of cells are discussed
      for screening of oral and cervical mucosa, and circulating tumor cells. It is
      concluded that infrared and Raman spectroscopy can complement histopathology and
      reveal information that is available in classical methods only by costly and time
      consuming steps such as immunohistochemistry, polymerase chain reaction or gene
      arrays. Due to the inherent sensitivity toward changes in the bio-molecular
      composition of different cell and tissue types, vibrational spectroscopy can even
      provide information that is in some cases superior to that of any one of the
      conventional techniques.

PMID- 24311231
TI  - Non-invasive determination of pulmonary hypertension with dynamic contrast
      enhanced computed tomography: a pilot study.
AB  - OBJECTIVES: In this pilot study we explored whether contrast-material bolus
      propagation time and speed in the pulmonary arteries (PAs) determined by dynamic
      contrast-enhanced computed tomography (DCE-CT) can distinguish between patients
      with and without pulmonary hypertension (PH). METHODS: Twenty-three patients (18
      with and 5 without PH) were examined with a DCE-CT sequence following their
      diagnostic or follow-up right-sided heart catheterisation (RHC). X-ray
      attenuation over time curves were recorded for regions of interest in the main,
      right and left PA and fitted with a spline fit. Contrast material bolus
      propagation speeds and time differences between the peak concentrations were
      compared with haemodynamic parameters from RHC. RESULTS: Bolus speed correlated
      (rho = -0.55) with mean pulmonary arterial pressure (mPAP) and showed a good
      discriminative power between patients with and without PH (cut-off speed 317
      mm/s; sensitivity 100%/specificity 100%). Additionally, time differences between
      peaks correlated with mPAP (rho = 0.64 and 0.49 for right and left PA,
      respectively) and discrimination was achieved with sensitivity 100%/specificity
      100% (cut-off time 0.15 s) and sensitivity 93 %/specificity 80% (cut-off time
      0.45 s), respectively. CONCLUSIONS: Bolus propagation speed and time differences
      between contrast material peaks in the PA can identify PH. This method could be
      used to confirm the indication for RHC in patients screened for pulmonary
      hypertension. KEY POINTS: * Dynamic contrast-enhanced computed tomography (CT)
      can identify patients with pulmonary hypertension. * Bolus propagation speed in
      the pulmonary artery is reduced in pulmonary hypertension. * Peak-contrast
      propagation times provide a practical surrogate for speed. * This non-invasive
      technique could serve as a screening method for pulmonary hypertension. *
      Invasive right-sided heart catheterisations might be restricted to a smaller
      group of patients.

PMID- 24311236
TI  - Medical imaging, PACS, and imaging informatics: retrospective.
AB  - Historical reviews of PACS (picture archiving and communication system) and
      imaging informatics development from different points of view have been published
      in the past (Huang in Euro J Radiol 78:163-176, 2011; Lemke in Euro J Radiol
      78:177-183, 2011; Inamura and Jong in Euro J Radiol 78:184-189, 2011). This
      retrospective attempts to look at the topic from a different angle by identifying
      certain basic medical imaging inventions in the 1960s and 1970s which had
      conceptually defined basic components of PACS guiding its course of development
      in the 1980s and 1990s, as well as subsequent imaging informatics research in the
      2000s. In medical imaging, the emphasis was on the innovations at Georgetown
      University in Washington, DC, in the 1960s and 1970s. During the 1980s and 1990s,
      research and training support from US government agencies and public and private
      medical imaging manufacturers became available for training of young talents in
      biomedical physics and for developing the key components required for PACS
      development. In the 2000s, computer hardware and software as well as
      communication networks advanced by leaps and bounds, opening the door for medical
      imaging informatics to flourish. Because many key components required for the
      PACS operation were developed by the UCLA PACS Team and its collaborative
      partners in the 1980s, this presentation is centered on that aspect. During this
      period, substantial collaborative research efforts by many individual teams in
      the US and in Japan were highlighted. Credits are due particularly to the Pattern
      Recognition Laboratory at Georgetown University, and the computed radiography
      (CR) development at the Fuji Electric Corp. in collaboration with Stanford
      University in the 1970s; the Image Processing Laboratory at UCLA in the 1980s
      1990s; as well as the early PACS development at the Hokkaido University, Sapporo,
      Japan, in the late 1970s, and film scanner and digital radiography developed by
      Konishiroku Photo Ind. Co. Ltd. (Konica-Minolta), Japan, in the 1980-1990s. Major
      support from the US National Institutes of Health and other federal agencies and
      private medical imaging industry are appreciated. The NATO (North Atlantic Treaty
      Organization) Advanced Study Institute (ASI) sponsored the International PACS
      Conference at Evian, France, in 1990, the contents and presentations of which
      convinced a half dozen high-level US military healthcare personnel, including
      surgeons and radiologists, that PACS was feasible and would greatly streamline
      the current military healthcare services. The impact of the post-conference
      summary by these individuals to their superiors opened the doors for long-term
      support of PACS development by the US Military Healthcare Services. PACS and
      imaging informatics have thus emerged as a daily clinical necessity. 

PMID- 24311237
TI  - Undergraduate healthcare ethics education, moral resilience, and the role of
      ethical theories.
AB  - BACKGROUND: This article combines foundational and empirical aspects of
      healthcare education and develops a framework for teaching ethical theories
      inspired by pragmatist learning theory and recent work on the concept of moral
      resilience. It describes an exemplary implementation and presents data from
      student evaluation. OBJECTIVES: After a pilot implementation in a regular ethics
      module, the feasibility and acceptance of the novel framework by students were
      evaluated. RESEARCH DESIGN: In addition to the regular online module evaluation,
      specific questions referring to the teaching of ethical theories were added using
      simple (yes/no) and Likert rating answer formats. PARTICIPANTS AND RESEARCH
      CONTEXT: At the Bern University of Applied Sciences, a total of 93 students from
      2 parallel sub-cohorts of the bachelor's program in nursing science were sent the
      online survey link after having been exposed to the same modular contents. A
      total of 62% of all students participated in the survey. ETHICAL CONSIDERATIONS:
      The survey was voluntary and anonymous. Students were free to write their name
      and additional comments. FINDINGS: Students consider ethical theories-as taught
      within the proposed framework-as practically applicable, useful, and transferable
      into practice. DISCUSSION: Teaching ethical theories within the proposed
      framework overcomes the shortcomings described by current research. Students do
      not consider the mutually exclusive character of ethical theories as an
      insurmountable problem. CONCLUSION: The proposed framework is likely to promote
      the effectiveness of healthcare ethics education. Inspired by pragmatist learning
      theory, it enables students to consider ethical theories as educative playgrounds
      that help them to "frame" and "name" the ethical issues they encounter in daily
      practice, which is seen as an expression of moral resilience. Since it does not
      advocate a single ethical theory, but is open to the diversity of traditions that
      shape ethical thinking, it promotes a culturally sensitive, ethically reflected
      healthcare practice.

PMID- 24311238
TI  - 'Moral distress'--time to abandon a flawed nursing construct?
AB  - Moral distress has been characterised in the nursing literature as a major
      problem affecting nurses in all healthcare systems. It has been portrayed as
      threatening the integrity of nurses and ultimately the quality of patient care.
      However, nursing discourse on moral distress is not without controversy. The
      notion itself is conceptually flawed and suffers from both theoretical and
      practical difficulties. Nursing research investigating moral distress is also
      problematic on account of being methodologically weak and disparate. Moreover,
      the ultimate purpose and significance of the research is unclear. In light of
      these considerations, it is contended that the notion of moral distress ought to
      be abandoned and that concerted attention be given to advancing inquiries that
      are more conducive to improving the quality and safety of moral decision-making,
      moral conduct and moral outcomes in nursing and healthcare domains. 

PMID- 24311239
TI  - Host-plant protein and phenolic resin effects on larval growth and survival of a
      butterfly.
AB  - Euphydryas chalcedona prediapause larvae were reared on fertilized and control
      shrubs of the host plant,Diplacus aurantiacus. Larval growth was enhanced by high
      leaf nitrogen content and inhibited by high leaf phenolic resin content. Larvae
      fed less on leaves near the branch tip which contained a higher leaf resin
      content. The results agree with prior laboratory investigation that the dietary
      content of nitrogen andD. aurantiacus leaf resin are major determinants ofE.
      chalcedona larval growth and suggest that the phenolic leaf resin ofDiplacus may
      both deter and inhibit leaf herbivores. 

PMID- 24311240
TI  - Consumption and utilization of experimentally altered corn by southern armyworm:
      Iron, nitrogen, and cyclic hydroxamates.
AB  - The effects of differential leaf water, leaf nitrogen and cyclic hydroxamate
      (DIMBOA) concentrations in corn seedlings were analyzed for a polyphagous insect,
      the southern armyworm (Spodoptera eridania Cram.). Six different combinations of
      nutrients and allelochemicals [DIMBOA = 2,4-dihydroxy-7-methoxy(2H)-benzoxazin
      3(4H)-one] were generated using two corn genotypes (WF9 and CI3IA) and three
      fertility regimes (complete nutrient, Fe-deficient, and N-deficient solutions) in
      the University Biotron. Poorest larval growth was observed in the low-nitrogen
      treatments (1.2% and 1.7% leaf N) and was the result of both low consumption
      rates and high metabolic costs (low efficiency of conversion of digested food,
      ECD). Fastest growth rates were observed forthe larvae fed leaves from the high
      nitrogen treatments (4.6% and 4.4% leaf N). It is noteworthy that these
      treatments also contained the highest concentration of cyclic hydroxamates, which
      are generally believed to be the primary defensive chemicals mediating resistance
      against the European corn borer,Ostrinia nubilalis (Hubner). If these
      hydroxamates do have any deleterious or costly effects (perhaps accounting for a
      large portion of metabolic expenditures), the high digestibility of the leaf
      tissue and the increased consumption rates more than compensate, resulting in
      rapid growth (growth rate = consumption rate * approximate digestibility *
      efficiency of conversion of the digested food). These studies illustrate that
      variation in key nutrients and allelochemicals within a single plant species (Zea
      mays L.) may have significantly different effects upon various potential leaf
      chewing caterpillars, such as these armyworms versus corn borers (which cannot
      handle the cyclic hydroxamates, even if provided with young nutritious leaf
      tissues). 

PMID- 24311241
TI  - Polyunsaturated hydrocarbons in the stable fly.
AB  - Three triply-unsaturated hydrocarbons were identified from cuticular lipids of
      male and mixed-sex stable flies,Stomoxys calcitrans. The major compound, (Z,Z)
      1,7,13-pentacosatriene, and two minor compounds, (Z,Z)-1,7,13-tetracosatriene and
      (Z,Z)-1,7,13-tricosatriene, were synthesized. Samples of male and female stable
      flies that differed in age, seasonality, geographic origin, rearing conditions of
      adults, and methods of extraction were analyzed for the presence of these
      triolefins. Females were found to have small quantities of the same C25
      triolefin, which appeared to be identical to that in males. No evidence was seen
      for attraction of males or females to natural or synthetic triolefins. 

PMID- 24311242
TI  - Solvent effects on conformation of a sex pheromone ofCydia (Laspeyresia pomonella
      L.; Lepidoptera: Tortricidae: Olethreutinae), codlemone (8,10-dodecadienol).
AB  - The conformations of codlemone (8,10-dodecadienol) and of a model analog have
      been studied by CNDO calculations. Stable conformations are found for the folded
      forms when the polarity of the solvent is taken into account. 

PMID- 24311243
TI  - Behavioral bioassays of termite trail pheromones : Recruitment and orientation
      effects of cembrene-A inNasutitermes costalis (Isoptera: Termitidae) and
      discussion of factors affecting termite response in experimental contexts.
AB  - The monocyclic 14-membered ring diterpene, cembrene-A, previously identified as a
      nasutitermitine trail pheromone, was tested for its effectiveness as a trail
      pheromone inNasutitermes costalis. Artificial trails prepared from serial
      dilutions of racemic cembrene-A over a concentration range of 10(-1)-10(-6) mg/ml
      were ineffective in recruiting termites. Serial dilutions of racemic cembrene-A
      ranging in concentration from 10(-1) to 10(-5) mg/ml produced an orientation
      effect. Chiral cembrene-A produced recruitment in soldiers at 10(-1) and 10(-3)
      mg/ml and was less ineffective in recruiting workers. Soldiers always showed a
      lower and more variable recruitment response to chiral cembrene-A than to sternal
      gland extracts. The behavioral response to both chiral and racemic cembrene-A was
      different in quantity and quality from that observed for sternal gland extract.
      Based on the results of these behavioral tests, cembrene-A appears to be a
      generalized nasute orientation pheromone which may show recruitment properties at
      unnaturally high concentrations. 

PMID- 24311244
TI  - Allelopathic effects ofCitrus aurantium L. : I. Vegetational patterning.
AB  - Field observations on undisturbed stands of sour orange revealed thatCynodon
      dactylon, Chenopodium album, Avena sativa, andAmaranthus retroflexus were not
      able to grow normally and complete their life cycles under its canopies, although
      the same species grow well under adjacent trees of date palm. Investigations
      revealed that the failure of the test species to grow normally under sour orange
      was not due to competition for light, moisture and minerals or to differences in
      soil texture or pH. Soil under sour orange trees drastically reduced seed
      germination and/or seedling growth of test species. Aqueous extracts, decaying
      materials, and volatile compounds of senescent and nonsenescent sour orange
      leaves were found to inhibit seed germination and/or seedling growth of test
      species. Therefore, allelopathy appeared to be the basic factor responsible for
      the reduction in plant growth with competition propably accentuating its effects.

PMID- 24311245
TI  - Allelopathic effects ofCitrus aurantium L. : II. Isolation, characterization, and
      biological activities of phytotoxins.
AB  - In an earlier work, we found that the failure of herbaceous plants to grow under
      sour orange was mainly due to an allelopathic mechanism. Four nonvolatile
      inhibitors were isolated by paper chromatography. Color reactions of all the
      inhibitors indicated that they are phenolic in nature. On the other hand, five
      volatile inhibitors were detected by gas chromatography, four of which were
      terpenes. All inhibitors reduced seed germination and/or seedling growth
      ofAmaranthus retroflexus. 

PMID- 24311246
TI  - Use of dye-labeled protein as spectrophotometric assay for protein precipitants
      such as tannin.
AB  - Bovine serum albumin has been covalently labeled with Remazol brilliant blue R to
      provide a substrate for a convenient spectrophotometric assay for protein
      precipitants. The blue protein is especially useful for measuring protein
      precipitation by vegetable tannins because its absorption maximum is at a
      wavelength where plant pigments exhibit minimum absorption. Blue BSA has been
      used to determine, by competition experiments, the relative affinity of various
      proteins for tannins. A procedure for purifying condensed tannin from
      commercially available quebracho extract is described. 

PMID- 24311247
TI  - Responses of the amphipod crustaceanGammarus palustris to waterborne secretions
      of conspecifics and congenerics.
AB  - A choice-test apparatus designed to mimic field conditions was employed to test
      for the presence of waterborne attractants in the amphipod crustaceanGammarus
      palustris. It was found that both males and females were attracted to secretions
      from all conspecifics, but not to the secretions of a sympatric congener. When
      given the choice of secretions from different types of conspecifics, males
      behaved differently than females. Males were attracted more often to receptive
      females' and females were attracted more often to males' secretions. In the
      field, then, it is likely that all conspecifics travel toward each other, then
      sort themselves into competent heterosexual couples. The results suggest that
      this apparatus can be employed in future studies to determine the chemical nature
      of these pheromones. 

PMID- 24311248
TI  - Use of chemical variation and predation as plant defenses byEncelia farinosa
      against a specialist herbivore.
AB  - Larvae of the monophagous herbivore,Trirhabda geminata, selectively eat
      particular plants and plant parts of its natural host,Encelia farinosa.
      Measurements of leaf damage and larval positions on branches through time support
      this observation. Time-lapse movie photography revealed that larvae are
      sufficiently mobile to search most of a plant in a 48-hr period and that
      aggregations were the result of larval activity and not directly the result of
      oviposition. Experiments withT. geminata larvae on artificial diets containing a
      range of natural concentrations of chemical extracts fromE. farinosa leaves
      showed that the larvae grew significantly slower and had a lower overall
      survivorship at the high concentration. Combining the results of all choice
      tests, larvae appeared unable to distinguish between high- and low-concentration
      agar diets. Considered individually, larval preferences for natural production
      concentrations changed as the season progressed. Early-season larvae preferred
      low-concentration leaves, while late-season larvae preferred high-concentrations.
      Measurements of chemical and nitrogen content of leaves selected by larvae in the
      field confirmed this pattern. Percent parasitism in field-collected larvae
      increased with season as the larval population decreased. This combination of
      slowed growth and increasing parasitism and predation is a putative defense
      strategy ofEncelia farinosa to prevent adaptation by a specialist herbivore to
      the total range of compounds elaborated. 

PMID- 24311249
TI  - Effects of ferulic andp-coumaric acids in nutrient culture of cucumber leaf
      expansion as influenced by pH.
AB  - Cucumber seedlings were grown in 5 mM MES [2-(N-morpholino)ethanesulfonic acid] 
      buffered nutrient solutions adjusted to a pH of 5.5, 6.25, or 7.0. Nutrient
      solutions were changed on alternate days. Seedlings were treated for a two-day
      period with various concentrations (0-1 mM) of ferulic acid,p-coumaric acid, or
      mixtures of these phenolic acids when 16 days old. Leaf growth, dry weight, and
      water utilization of the seedlings; pH of the solutions; and disappearance of the
      phenolic acids from nutrient solutions were monitored. Leaf area expansion of
      cucumber seedlings was inhibited by both ferulic andp-coumaric acid, and the
      magnitude of these inhibitions was influenced by concentration and pH. Inhibition
      of leaf area expansion was greater at pH 5.5 and nominal at pH 7.O. Ferulic acid
      was more inhibitory thanp-coumaric acid. The effect of pH on growth was best
      described by data for mean relative rates of leaf expansion. For example, the
      mean relative rates of leaf expansion by both acids at 0.5 mM for the 16- to 18
      day growth period (treatment period) were reduced by 45, 31, and 8% for the pH
      5.5, 6.25, and 7.0 treatments, respectively. The dry weight of seedlings at
      harvest (day 22) was significantly reduced for seedlings grown in the pH 5.5 and
      6.25 treatments, but not for the pH 7.0 treatment. There was, however, one
      exception; the dry weight of seedlings treated withp-coumaric acid solutions
      adjusted to a pH of 5.5 was not significantly reduced. Water utilization by the
      seedlings was reduced by both ferulic andp-coumaric acid. Again, the impact of
      ferulic acid was greater thanp-coumaric acid. The effect of ferulic acid on water
      utlization decreased with increasing pH of the nutrient solution. The pH effects
      were not so consistent forp-coumaric acid. The effects of equimolar mixtures of
      the two phenolic acids were additive for all variables measured. There was a
      linear correlation between mean relative rates of leaf expansion and water
      utilization. 

PMID- 24311250
TI  - Response specificity of male pink bollworm moths to different blends and dosages
      of sex pheromone.
AB  - Male pink bollworm,Pectinophora gossypiella, were tested in a sustained flight
      tunnel to 119 blend-dosage combinations of the sex pheromone components, (Z,Z)-
      and (Z,E)-7,11-hexadecadienyl acetates, which are released by conspecific females
      in a 61?39 ratio. Hierarchical cluster analysis was used to define an area of
      peak attraction. Within this area males were most sensitive at lower dosages to
      ratios around the natural blend of components, but exhibited peak response levels
      at higher dosages to a wide range of blends, with a shift in blend preference to
      higherZ,Z isomer ratios at the highest dosage tested (10 mg). Male response
      specificity appeared to be influenced exclusively by a threshold for initiation
      of upwind flight, and not arrestment of upwind flight. The results are compared
      with those of another species, the Oriental fruit moth. 

PMID- 24311252
TI  - The inside of life.

PMID- 24311251
TI  - WNT10A mutations also associated with agenesis of the maxillary permanent
      canines, a separate entity.
AB  - Agenesis or isolated hypodontia of the maxillary permanent canines is a very rare
      dental anomaly. We report on nine unrelated Thai patients with this condition.
      Three of them had one affected parent. Three heterozygous missense mutations
      (p.Arg171Cys; p.Gly213Ser; and IVS2+1G>A) were identified in WNT10A in six
      patients. The p.Gly213Cys mutation was found in four patients. One of the
      patients who had p.Gly213Ser mutation also had peg-shaped (microdontia of the)
      maxillary lateral incisors with dens invaginatus. The mothers of two patients who
      carried the same mutation as their affected sons (p.Gly213Ser and p.Arg171Cys)
      had microdontia of the maxillary permanent lateral incisor. Our study has
      demonstrated for the first time that agenesis of the maxillary permanent canines
      is a distinct entity, associated with mutations in WNT10A. Inheritance appears to
      be autosomal dominant. Agenesis of the maxillary permanent canines may accompany
      by microdontia of the maxillary permanent lateral incisors and dens invaginatus
      of the maxillary permanent lateral incisors. Mutations could not be identified in
      the coding exons of WNT10A in three patients. They might be located outside the
      coding exons, including the promoter regions. However, it is likely that agenesis
      of the maxillary permanent canines is a heterogeneous disorder.

PMID- 24311253
TI  - Values and the moral context of pastoral counseling.
AB  - This paper reviews the ways in which psychology has influenced the pastoral
      counseling movement, focuses, upon how the role and function of the pastoral
      counselor have lost their unique identity, and offers the construct of a moral
      context as a means for rediscovering, identifying, reviving, and strengthening
      the pastoral counselor's professional and spiritual selfimage. 

PMID- 24311254
TI  - The perspective of evil in understanding and treating child abuse.
AB  - This paper places the problem of child abuse in the perspective of evil. In so
      doing it calls into question the amoral assumptions of social science and human
      services. The current social science paradigm paradoxically dismisses evil as a
      real factor in the world, despite its concern for indisputably moral issues such
      as child abuse. The practical advantages of a perspective incorporating evil are
      several. Among them are a more realistic appreciation of the need for mechanisms
      of social control in preventing abuse, the role of confession and conversion, and
      the role of pastoral care as a support system for families. 

PMID- 24311255
TI  - Anorexia nervosa: A pastoral update.
AB  - Anorexia nervosa is a disorder of unknown etiology that is a complex of physical,
      emotional, and behavioral changes occurring in individuals who starve themselves.
      The incidence of this disease has increased dramatically in the last twenty
      years. Most patients seem to be unaware of or unconcerned about their emaciation.
      After presenting a case, this study reviews the most recent findings about this
      disease, including the symptoms, social characteristics of its victims, increaed
      incidence, history, and prognosis. Suggestions are offered for pastoral care and
      counseling. 

PMID- 24311256
TI  - Developmental tasks of terminally ill patients.
AB  - Erikson's epigenetic stages provide a conceptual map of how a person responds to
      the knowledge of having a terminal illness. The patient initially reworks
      developmental tasks that have been resolved and then works at an accelerated pace
      to accomplish tasks that remain ahead. This acceleration is an attempt to attain
      a wholeness of self and life in light of the threat of imminent death and self
      perceived shortened life span. 

PMID- 24311257
TI  - Systematic review and meta-analysis of use of serum C-reactive protein levels to
      predict anastomotic leak after colorectal surgery.
AB  - BACKGROUND: Several recent studies have investigated the role of C-reactive
      protein (CRP) as an early marker of anastomotic leakage following colorectal
      surgery. The aim of this systematic review and meta-analysis was to evaluate the
      predictive value of CRP in this setting. METHODS: A systematic literature search
      was performed using MEDLINE, Embase and PubMed to identify studies evaluating the
      diagnostic accuracy of postoperative CRP for anastomotic leakage following
      colorectal surgery. A meta-analysis was carried out using a random-effects model
      and pooled predictive parameters were determined along with a CRP cut-off value
      at each postoperative day (POD). RESULTS: Seven studies, with a total of 2483
      patients, were included. The pooled prevalence of leakage was 9.6 per cent and
      the median day on which leakage was diagnosed ranged from POD 6 to 9. The serum
      CRP level on POD 3, 4 and 5 had comparable diagnostic accuracy for the
      development of an anastomotic leak with a pooled area under the curve of 0.81 (95
      per cent confidence interval 0.75 to 0.86), 0.80 (0.74 to 0.86) and 0.80 (0.73 to
      0.87) respectively. The derived CRP cut-off values were 172 mg/l on POD 3, 124
      mg/l on POD 4 and 144 mg/l on POD 5; these corresponded to a negative predictive
      value of 97 per cent and a negative likelihood ratio of 0.26-0.33. All three time
      points had a low positive predictive value for leakage, ranging between 21 and 23
      per cent. CONCLUSION: CRP is a useful negative predictive test for the
      development of anastomotic leakage following colorectal surgery.

PMID- 24311258
TI  - Modulation of glucose-6-phosphate dehydrogenase by NADPH, NADP(+) and
      dithiothreitol at variable NADPH/NADP (+) ratios in an illuminated reconstituted
      Spinach (Spinacia oleracea L.) chloroplast system.
AB  - The light-dependent inhibition of glucose-6-phosphate dehydrogenase (EC
      1.1.1.49), the key enzyme of the oxidative pentose phosphate cycle, can be
      gradually abolished in an illuminated reconstituted spinach chloroplast system by
      increasing the concentration of NADP(+). The inhibition caused by the effector
      which was produced by the system in the light is characterized as being of the
      competitive type with respect to NADP(+). The Ki value is 0.070 mM. The addition
      of NADPH to the illuminated reconstituted system results in a further decrease of
      the enzyme activity. Again, the type of inhibition is a competitive one, the Ki
      value being 0.072 mM. In the presence of dithiothreitol (DTT) alone the
      inhibition is incomplete, non-competitive, and the Ki value is as high as 0.2 mM.
      From the data presented it is concluded that light modulation of chloroplast
      glucose-6-phosphate dehydrogenase is mainly achieved by the NADPH/NADP(+) ratio.
      Disulfide reduction processes induced by a DTT-type compound seem to play a minor
      physiologic role during illumination. 

PMID- 24311259
TI  - Glutamate dehydrogenase from Pisum sativum L. : Localization of the multiple
      forms and of glutamate formation in isolated mitochondria.
AB  - A 2-8-fold increase in the activity of glutamate dehydrogenase (GDH), accompanied
      by an alteration of the GDH isoenzyme pattern, was observed in detached pea
      shoots floated on tap water (preincubated shoots). Sugars supressed the process,
      whereas NH + (4) and various metabolites as well as inhibitors of energy
      metabolism and protein synthesis were ineffective. The subcellular distribution
      pattern revealed evidence that the GDH isoenzymes are exclusively located in the
      mitochondrial matrix. The alterations in GDH activity occurring in preincubated
      shoots are restricted to the mitochondria.An experimental device suitable for
      studying the GDH function in isolated intact mitochondria has been established.
      Using [(14)C] citrate as the carbon source and hydrogen donor, the mitochondria
      synthesized considerable amounts of glutamate upon addition of NH + (4) . The
      rates of glutamate formation in dependency of increasing NH + (4) levels follow
      simple Michaelis-Menten kinetics. Half-saturation concentrations of NH + (4) of
      3.6+/-1.2 mM; 1.9+/-0.06 mM and 1.6+/-0.1 mM were calculated for the mitochondria
      isolated from pea shoots, roots, and preincubated shoots, respectively. The
      results are discussed in relation to the possible role of GDH in NH+/4
      assimilation at elevated intracellular NH+/4 levels. 

PMID- 24311260
TI  - Ribosomal RNA synthesis in imbibing radish (Raphanus sativus) embryo axes : A
      biochemical and cytological study.
AB  - The first hours of seed germination are characterized by an increase in the rate
      of RNA synthesis. Although this change is most easily accounted for by changes in
      the ribonucleotide pool sizes, we investigated two other aspects of rRNA
      synthesis which are likely to contribute to the phenomenon. Using isolated radish
      embryo axes, we demonstrate that processing of rRNA gene transcripts is much
      slower during early germination than during the growth of the seedling. We also
      provide evidence that rRNA gene expression is sequentially reactivated in
      different tissues, starting in the provascular tissue and apex cells and only
      later in the cortical cells of the rootlet. 

PMID- 24311261
TI  - Rate of synthesis of spermine and spermidine in germinating seeds of Glycine,
      Helianthus and Triticum.
AB  - The spermine, spermidine, and the total protein content of embryos or embryonic
      axes from Triticum durum, Helianthus annuus, and Glycine max seeds at different
      times of early germination was evaluated. Mitotic activity of root-tip meristems
      from germinating seeds was also determined. The hypothesis is suggested that
      differences in polyamine and protein pattern during early germination could be
      correlated with the onset of mitotic activity and with the different
      characteristics of the seeds assayed. 

PMID- 24311262
TI  - Osmoregulation and the control of phloem-sap composition in Ricinus communis L.
AB  - Phloem-sap composition was studied in plants of Ricinus communis L. grown on a
      waterculture medium. The sap possessed a relatively high K(+):Na(+) ratio and low
      levels of Ca(2+) and free H(+). Sucrose and K(+) (together with its associated
      anions) accounted for 75% of the phloem-sap solute potential (Psis). In plants
      kept in continuous darkness, a decrease in phloem-sap sucrose levels over 24h was
      accompanied by an increase in K(+) levels. Measurements of phloem-sap Psis and
      xylem water potential (Psi) indicated that this resulted in a partial maintenance
      of phloem turgor pressure Psip. In darkness there was also a marked decrease in
      the malate content of the leaf tissue, and it is possible that organic carbon
      from this source was mobilized for export in the phloem. The results support the
      concept of the phloem sap as a symplastic phase. We interpret the increase in
      K(+) levels in the phloem in darkness as an osmoregulatory response to conditions
      of restricted solute availability. This reponse can be explained on the basis of
      the sucrose-H(+) co-transport mechanism of phloem loading. 

PMID- 24311263
TI  - Phloem transport, solute flux and the kinetics of sap exudation in Ricinus
      communis L.
AB  - The osmotic characteristics of phloem-sap exudation were examined in soil-grown
      and watercultured plants of Ricinus communis L. Prolonged exudation occurred from
      bark incisions in water-cultured plants. Fresh incisions caused large alterations
      in solute flux, but phloem-sap solute potential Psis changed by less than +/-8%
      over a period of 7 h. This was associated with a constancy in the levels of
      sucrose and K(+), the principal solutes in the sap. Studies with foliar-applied
      tracers and leaf-excision experiments suggested that exudation was maintained by
      solute loading from mature leaves. A wide range of mass transfer values through
      the phloem was found, these being a function of exudation rate. We consider that
      the exudation process possesses essentially similar characteristics to phloem
      transport in the intact plant. The way in which bark incisions bring about large
      changes in solute flux is discussed in terms of the physical properties of the
      sieve-tube system. 

PMID- 24311264
TI  - Phloem turgor and the regulation of sucrose loading in Ricinus communis L.
AB  - The influence of plant water relations on phloem loading was studied in Ricinus
      communis L. Phloem transport was maintained in response to bark incisions even at
      severe water deficits. Water stress was associated with a net increase in the
      solute content of the sieve tubes, which resulted in maintenance of a positive
      phloem turgor pressure Psip. There was a significant increase in solute flux
      through the phloem with decreasing xylem water potential (Psi). In addition,
      sugar uptake by leaf discs was examined in media adjusted to different water
      potentials with either sorbitol (a relatively impermeant solute) or ethylene
      glycol (a relatively permeant solute). The limitations in this experimental
      system are discussed. The results nevertheless indicated that sucrose uptake can
      be stimulated by a reduction in cell Psip, but that it is little affected by cell
      Psi or solute potential Psis. On the basis of these data we suggest that sucrose
      loading is turgor-pressure dependent. This may provide the mechanism by which
      transport responds to changes in sink demand in the whole plant. 

PMID- 24311265
TI  - Characterisation of the storage protein subunits synthesised in vitro by
      polyribosomes and RNA from developing pea (Pisum sativum L.) : I. Legumin.
AB  - Evidence is presented to show that legumin, the major storage protein in Pisum,
      is synthesised in vitro by the wheat germ and reticulocyte lysate systems, from
      polyribosomes and mRNA isolated from developing pea seeds. While legumin isolated
      from mature pea seeds consists of 40,000 and 20,000 MW subunits, the in vitro
      legumin is synthesised as a 60,000 MW precursor consisting of covalently linked
      40,000 and 20,000 MW subunits. The implications of these findings are discussed
      in relationship to studies with other systems. 

PMID- 24311266
TI  - Characterisation of the storage protein subunits synthesised in vitro by
      polyribosomes and RNA from developing pea (Pisum sativum L.) : II. Vicilin.
AB  - Polypeptide material has been immunoprecipitated by antivicilin antibodies from
      translation products of polyribosomes and poly(A)-rich RNA isolated from
      developing seeds of Pisum sativum in the wheat germ and reticulocyte lysate cell
      free synthesis systems. Analysis of this material by SDS-PAGE shows it to consist
      of three bands, of molecular weights 70,000, 50,000 and 47,000. The in vitro
      vicilin polypeptides of 70,000 and 50,000 mol. wt. have been shown to be very
      similar to the 70,000 and 50,000 mol. wt. subunits of vicilin by specific
      immunoprecipitation, and behaviour on treatment with cyanogen bromide and
      trypsin. The 50,000 mol. wt. in vitro vicilin polypeptide contains no significant
      extra sequence compared to the 50,000 mol. wt. vicilin subunit. The 47,000 mol.
      wt. in vitro vicilin polypeptide has no corresponding subunit in vicilin from
      mature seeds, but a 47,000 mol. wt. subunit is present in vicilin isolated from
      developing seeds. Comparison of translation products from polysomes isolated from
      seeds at middle and late stages of development shows that synthesis of the 50,000
      and 47,000 mol. wt., but not 70,000 mol. wt. polypeptides is very much reduced at
      late stages of development. These results are discussed with reference to the
      nature of the vicilin fraction. 

PMID- 24311267
TI  - Ethylene, gibberellins, auxin and the apical control of branch angle in a
      conifer, Cupressus arizonica.
AB  - Decapitation, gibberellin A3, high light, their combination, and certain levels
      of indole-3-acetic acid increase ethylene evolution and also induce branch
      hyponasty (upturning) in seedlings of Cupressus arizonica Greene, the increase in
      ethylene preceding obvious hyponasty. Exogenous ethylene also causes branch
      hyponasty and branches of seedlings maintained in an atmosphere scavenged of
      ethylene by mercuric perchlorate grow downwards. It is concluded that ethylene
      may play a role in the apical control of branch angle in some conifers. The
      positive effect of ethylene in increasing branch hyponasty may be direct, or
      reflect changes in levels of endogenous auxin and/or gibberellin. 

PMID- 24311268
TI  - Free tryptophan and indole-3-acetic acid levels in the leaves and vascular
      pathways of Ricinus communis L.
AB  - Levels of free tryptophan in the leaves, phloem and xylem saps of Ricinus
      communis L. were determined by colorimetric assay. Values of 0.38 MUg ml(-1) in
      root pressure sap and 96.0 MUg ml(-1) in phloem sap were recorded. Tryptophan
      levels were highest in mature and senescing leaves. Levels of indoleacetic acid
      (IAA) in the phloem sap and leaves were determined by gas chromatography-mass
      spectrometry using a deuterated internal standard. A mean value of 13.0 ng ml(-1)
      was recorded in phloem sap. The distribution in the leaves showed an inverse
      relationship to that of tryptophan, being highest in young leaves. 

PMID- 24311269
TI  - A rapid method for isolation of purified, physiologically active chloroplasts,
      used to study the intracellular distribution of amino acids in pea leaves.
AB  - A procedure is described for the rapid (<5 min) isolation of purified,
      physiologically active chloroplasts from Pisum sativum L. Mitochondrial and
      microbody contamination is substantially reduced and broken chloroplasts are
      excluded by washing through a layer containing a treated silica sol. On average
      the preparations contain 93% intact chloroplasts and show high rates of (14)CO2
      fixation and CO2-dependent O2 evolution (over 100 MUmol/mg chlorophyll(chl)/h);
      they are also able to carry out light-driven incorporation of leucine into
      protein (4 nmol/mg chl/h). The amino-acid contents of chloroplasts prepared from
      leaves and from leaf protoplasts have been determined. Asparagine is the most
      abundant amino acid in the pea chloroplast (>240 nmol/mg chl), even thought it is
      proportionately lower in the chloroplast relative to the rest of the cell. The
      chloroplasts contain about 20% of many of the amino acids of the cell, but for
      individual amino acids the percentage in the chloroplast ranges from 8 to 40% of
      the cell total. Glutamic acid, glutamine and aspartic acid are enriched in the
      chloroplasts, while asparagine, homoserine and beta-(isoxazolin-5-one-2-yl)
      alanine are relatively lower. Leakage of amino acids from the chloroplast during
      preparation or repeated washing was ca. 20%. Some differences exist between the
      amino-acid composition of chloroplasts isolated from intact leaves and from
      protoplasts. In particular, gamma-aminobutyric acid accumulates to high levels,
      while homoserine and glutamic acid decrease, during protoplast formation and
      breakage. 

PMID- 24311270
TI  - Topographical features of the membrane of Poterioochromonas malhamensis after
      colchicine and osmotic treatment.
AB  - Changes in membrane topography in the flagellate Poterioochromonas malhamensis,
      as a result of colchicine and osmotic-stress treatments, have been studied using
      freeze-fracturing and thin sectioning. Ridges, but not rows of intramembrane
      particles, in the PF-face which denote the position of underlying cortical
      microtubules, together with the ridge associated with their point of origin
      (flagellar root fibre 1), dissappear after colchicine or short-term (5 min)
      osmotic treatments. Cortical microtubules are destroyed as a result of the
      former, but not the latter treatment. Longer periods in osmoticum allow a
      recovery of the microtubule - associated membrane ridges. Despite careful
      isosmotic fixations distinct cross-bridges between microtubules and the
      plasmalemma were not discernible in thin section. 

PMID- 24311271
TI  - Different regeneration potential of mesophyll protoplasts from cultivated and a
      wild species of tomato.
AB  - Mesophyll protoplasts were isolated from leaves of three cultivars of
      Lycopersicon esculentum (L.) Mill., namely "Hilda 72", "Rutgers" and "Rentita",
      and from the wild tomato species Lycopersicon peruvianum (L.) Mill. Protoplasts
      from L. peruvianum divided and grew actively in a liquid medium according to
      Zapata et al. (1977), whereas protoplasts from the tomato cultivars "Hilda 72"
      and "Rutgers" showed comparable rates for cell division only, when the content of
      major elements in this medium was reduced to one half of the original
      concentration and when mannitol as osmoticum was replaced by glucose. In
      "Rentita" protoplasts no cell division could be observed in about 15 different
      modifications of the five basic culture media tested. The morphogenetic potential
      of these tomato cells was assessed by comparing the root and shoot formation of
      protoplasts and of leaf explants. L. peruvianum exhibited the highest potential.
      Calli derived from protoplasts regenerated roots on Murastrige-Skoog agar
      containing 1 MUM benzylaminopurine (BAP) plus 10 MUM indole-3-acetic acid (IAA)
      and 0.1 MUM BAP plus 1 MUM IAA. Shoot formation occurred in the combinations of
      10 MUM BAP with 0.1, 1.0, and 10 MUM IAA. Plantlets regenerated from the L.
      peruvianum calli could be grown in soil. No shoots or roots were regenerated from
      calli of "Hilda 72" and "Rutgers" protoplasts in all combinations of BAP and IAA
      tested in the range from 0.1 MUM to 100 MUM, thus indicating the rather low
      morphogenetic potential of these protoplasts as compared to protoplasts from L.
      peruvianum leaves. 

PMID- 24311272
TI  - Top-hat and asymmetric Gaussian-based fitting functions for quantifying
      directional single-molecule motion.
AB  - Single-molecule fluorescence permits super-resolution imaging, but traditional
      algorithms for localizing these isolated fluorescent emitters assume stationary
      point light sources. Proposed here are two fitting functions that achieve similar
      nanometer-scale localization precision as the traditional symmetric Gaussian
      function, while allowing, and explicitly accounting for, directed motion. The
      precision of these methods is investigated through Fisher information analysis,
      simulation and experiments, and the new fitting functions are then used to
      measure, for the first time, the instantaneous velocity and direction of motion
      of live bacteria cells. These new methods increase the information content of
      single-molecule images of fast-moving molecules without sacrificing localization
      precision, thus permitting slower imaging speeds, and our new fitting functions
      promise to improve tracking algorithms by calculating velocity and direction
      during each image acquisition. 

PMID- 24311273
TI  - Comparing distance metrics for rotation using the k-nearest neighbors algorithm
      for entropy estimation.
AB  - Distance metrics facilitate a number of methods for statistical analysis. For
      statistical mechanical applications, it is useful to be able to compute the
      distance between two different orientations of a molecule. However, a number of
      distance metrics for rotation have been employed, and in this study, we consider
      different distance metrics and their utility in entropy estimation using the k
      nearest neighbors (KNN) algorithm. This approach shows a number of advantages
      over entropy estimation using a histogram method, and the different approaches
      are assessed using uniform randomly generated data, biased randomly generated
      data, and data from a molecular dynamics (MD) simulation of bulk water. The
      results identify quaternion metrics as superior to a metric based on the Euler
      angles. However, it is demonstrated that samples from MD simulation must be
      independent for effective use of the KNN algorithm and this finding impacts any
      application to time series data.

PMID- 24311274
TI  - An optimized Fmoc synthesis of human defensin 5.
AB  - Human alpha-defensin 5 (DEF5), expressed by the Paneth cells of human small
      intestine, plays an important role in host defense against microbial infections.
      DEF5, a 32-residue peptide adopting a three-stranded beta-sheet fold stabilized
      by three internal disulfide bonds, is not efficiently produced by recombinant
      expression techniques and is, therefore, an interesting goal for chemical
      synthesis. While DEF5 production by Boc-based solid-phase synthesis has been
      described, to date no synthetic account by the more convenient Fmoc method has
      been published. Herein, we report an optimized solid-phase synthesis of DEF5
      using the Fmoc strategy. Starting from a rather problematic initial synthesis
      using standard Wang resin and coupling protocols, the sequence elongation process
      has been monitored by mini-cleavage and MS analysis at strategic points, to
      identify problematic spots and act accordingly. For expediency, some of the
      optimization rounds have been run on defensin 5 amide. Main modifications have
      included the ChemMatrix((r)) resin, known to decrease chain aggregation, and the
      use of pseudoproline dipeptide units at selected positions. Combination of some
      of these improvements results in a significantly purer product, to the extent
      that it can undergo in situ anaerobic oxidative folding to the native form
      without the need of an intermediate purification step. A typical synthesis run
      yielded about 15 mg of >95 % pure material. This approach should facilitate
      production of DEF5 and of selected analogs for structure-activity studies and
      other applications.

PMID- 24311275
TI  - Microvesicle-shuttled miR-130b reduces fat deposition in recipient primary
      cultured porcine adipocytes by inhibiting PPAR-g expression.
AB  - Obesity is a worldwide epidemic, and a risk factor for cardiovascular disease and
      type 2 diabetes. Consequently, the development of safe and effective anti-obesity
      drugs is an area of ongoing clinical interest. MicroRNAs play a vital role in
      anti-obesity by inhibiting the expression of genes involved in adipogenesis and
      lipogenesis. However, the clinical application of miRNAs has been limited by a
      lack of appropriate delivery systems. The discovery of microvesicles (MVs) has
      shed new light on the search for more efficient drug transport tools. In a
      previous study, we demonstrated that miRNA-130b suppressed fat deposition by
      inhibiting PPAR-g expression. In order to demonstrate whether miRNA-130b can be
      packaged into MVs and function as an endogenous form of miRNA-130b in recipient
      cells, we transfected HeLa-229 cells with plasmid to overexpress miRNA-130b. This
      enabled HeLa-229 cells to selectively package miRNA-130b into MVs and actively
      secrete the miRNA-130b enriched MVs into the culture media. We further verified
      that MVs enriched with miRNA-130b contain elevated concentrations of Argonaute 2
      and heat shock protein 90a which are known to protect the circulating miRNAs from
      degradation. Exposure of primary cultured porcine adipocytes to purified, miRNA
      130b-enriched MVs resulted in a significant down-regulation of PPAR-g expression
      which was associated with reduced adipogenesis and lipogenesis. Taken together,
      our results suggest that MVs may provide an effective transport systems for the
      deliver of miRNAs for therapeutic use. We also showed that MV-shuttled miRNA-130b
      inhibited adipogenesis and lipogenesis, and reduced fat deposition in recipient
      adipocytes by targeting PPAR-g.

PMID- 24311276
TI  - Enrichment for heterokaryocytes by the use of iso-osmotic density gradients after
      plant protoplast fusion.
AB  - Buoyant density differences between different types of protoplasts were used in
      an iso-osmotic density gradient system to enrich protoplast fusion mixtures for
      heterokaryocytes. Protoplasts of maize stem and wheat mesophyll, as well as
      epidermis, stem parenchyma and mesophyll protoplasts of two amphihaploid, light
      sensitive tobacco mutants were fused with polyethylene glycol using conventional
      methods and a new rolling tube technique. The protoplast combinations used for
      fusion involved protoplast types with considerably different buoyant densities.
      Enriched fractions of maize-wheat heterokaryocytes of intermediate density were
      recovered which contained up to 31% mostly binucleate heterokaryocytes (a 2-7
      fold relative enrichment). Tobacco heterokaryocytes recovered analogously from
      enriched intermediate fractions readily divided and gave rise to an increased
      number of light resistant calluses when compared with cultures from non
      fractionated fusion mixtures. Maize-wheat fusion products, however, failed to
      divide. 

PMID- 24311277
TI  - Fractionation of plant protoplast types by iso-osmotic density gradient
      centrifugation.
AB  - A simple effective technique for the fractionation of protoplast populations is
      described. Protoplasts are separated by low-speed centrifugation in an iso
      osmotic, discontinuous density gradient system on the basis of differences in
      their buoyant densities. At a constant osmolality of 660+/-20 mOs/kg H2O, the
      gradients provide a density range from 1.017 to 1.069 g/cm(3) at 20  degrees C
      which corresponds to the buoyant densities of most protoplast types studied.
      Characteristics of the KMC/S-density gradient system and factors affecting the
      fractionation were investigated. Protoplasts were isolated from various tissues
      and cultivars of tobacco, barley, wheat, rye, oat and maize. Their density
      dependent distribution profiles in KMC/S-gradients and their average buoyant
      densities were determined under standardized conditions. Great differences in the
      buoyant densities were found between protoplasts of different tissues. Mixed
      populations of two types of protoplasts, differing in buoyant density by about 15
      20 mg/cm(3), were separated to give highly purified fractions. Factors affecting
      the buoyant densities of protoplasts have been investigated. Ploidy level and
      species differences did not significantly affect the fractionation profiles.
      However, an age-dependent variation in the average buoyant density of tobacco
      mesophyll protoplasts was observed. Fractionation of tobacco mesophyll
      protoplasts and their subsequent regeneration to plants demonstrates the
      practicability and physiological compatibility of the KMC/S-density gradient
      system under sterile conditions. The morphogenetic potential of protoplasts was
      not affected by the separation procedure or the gradient components. 

PMID- 24311278
TI  - Genetic load and viability variation in korean natural populations of Drosophila
      melanogaster.
AB  - Natural populations of Drosophila melanogaster from Anyang and Susac (suburbs of
      Seoul) have been analyzed with respect to viability variation on the second
      chromosome. Homozygotes as well as random heterozygotes for wild chromosomes were
      studied. The frequency of lethal factors was about 16 per cent, that of drastics
      26 per cent. The average viability of homozygotes was 0.650 including lethal
      lines and 0.858 for quasinormals; that for random heterozygotes was 1.125.
      Allelism tests have been performed for the lethals. The allelism rate turned out
      to be as high as 0.036 and 0.0214, respectively. Using a formula by Nei, the
      effective population size can be estimated from these data. Korean D.
      melanogaster populations proved as small as 2000 to 3000 individuals. No
      correlation between homozygous and heterozygous viabilities could be found.
      According to these observations, along with the fact that partly big clusters of
      identic lethals could be found in the allelism tests, it is concluded that in
      Korean populations quite a large part of the hard genetic load is balanced. The
      connection between population size, population structure and associative or
      genuine overdominance is discussed. 

PMID- 24311279
TI  - Selection of individual tubers in potato breeding.
AB  - Out of 720 field-grown potato first year seedlings plants with best tuber
      apearance and large and medium size tubers with best shape were respectively
      selected. The tuber progeny of each group was evaluated in field experiments. It
      was demonstrated that the selection of individual tubers was very effective in
      the elimination of clones with irregular tuber shape and deep eyes. The tuber
      progeny of selected tubers was not inferior to the tuber progeny of selected
      plants. Possible applications of the results to practical potato breeding are
      discussed. 

PMID- 24311280
TI  - The inheritance of partial self-compatibility in Brassica oleracea L.: results
      from a half diallel homozygous for a highly recessive S-allele.
AB  - In a study of partial self-compatbility in Brassica oleracea, flower number,
      seeded siliqua and seed production were recorded on self- and cross-pollinated
      inflorescences of the progenies of a half diallel between five unrelated inbred
      plants homozygous for the same recessive S-allele.On cross-pollinated
      inflorescences significant amounts of additively controlled genetic variation
      were found for seed set per flowering site and its two components, seeded
      siliquae per flower and seeds per seeded siliquae. Considerable heterosis and
      gene interaction were also present and a simple additive dominance model did not
      fully explain the observed variation.On self-pollinated inflorescences, additive
      gene action was absent for the seed production variates although differences
      between progenies were highly significant and heterosis was present. Complex gene
      interactions were considered to be responsible. The characteristics of the method
      of assessment used and the relationship between self- and outcross seed
      production are discussed. It appears unlikely that the component lines could be
      selected for reduced self seed set, but selection for higher outcross seed set
      may be possible. 

PMID- 24311281
TI  - Limitations of conventional regression analysis a proposed modification.
AB  - The conventional genotype-environment interaction analysis cannot detect the
      theoretically ideal genotype which has been defined as the one with relatively
      low sensitivity in the poor environments and high sensitivity in the favourable
      environments.The computation of separate regression coefficients on the two
      regions of the response curve has been suggested to detect such genotypes. This
      procedure is simple and more convenient than the complicated curvilinear
      regression analysis. 

PMID- 24311282
TI  - Integrated population pharmacokinetic/viral dynamic modelling of
      lopinavir/ritonavir in HIV-1 treatment-naive patients.
AB  - BACKGROUND: Lopinavir (LPV)/ritonavir (RTV) co-formulation (LPV/RTV) is a widely
      used protease inhibitor (PI)-based regimen to treat HIV-infection. As with all
      PIs, the trough concentration (C trough) is a primary determinant of response,
      but the optimum exposure remains poorly defined. The primary objective was to
      develop an integrated LPV population pharmacokinetic model to investigate the
      influence of alpha-1-acid glycoprotein and link total and free LPV exposure to
      pharmacodynamic changes in HIV-1 RNA and assess viral dynamic and drug efficacy
      parameters. METHODS: Data from 35 treatment-naive HIV-infected patients
      initiating therapy with LPV/RTV 400/100 mg orally twice daily across two studies
      were used for model development and simulations using ADAPT. Total LPV (LPVt) and
      RTV concentrations were measured by high-performance liquid chromatography with
      ultraviolet (UV) detection. Free LPV (LPVf) concentrations were measured using
      equilibrium dialysis and mass spectrometry. RESULTS: The LPVt typical value of
      clearance (CLLPVt/F) was 4.73 L/h and the distribution volume (VLPVt/F) was 55.7
      L. The clearance (CLLPVf/F) and distribution volume (Vf/F) for LPVf were 596 L/h
      and 6,370 L, respectively. The virion clearance rate was 0.0350 h(-1). The
      simulated LPVLPVt C trough values at 90% (EC90) and 95% (EC95) of the maximum
      response were 316 and 726 ng/mL, respectively. CONCLUSIONS: The pharmacokinetic
      pharmacodynamic model provides a useful tool to quantitatively describe the
      relationship between LPV/RTV exposure and viral response. This comprehensive
      modelling and simulation approach could be used as a surrogate assessment of
      antiretroviral (ARV) activity where adequate early-phase dose-ranging studies are
      lacking in order to define target trough concentrations and possibly refine
      dosing recommendations.

PMID- 24311283
TI  - A microbiologist's odyssey: Bacterial viruses to photosynthetic bacteria.
AB  - Perspective can be defined as the relationships or relative importance of facts
      or matters from any special point of view. Thus, my Personal perspective reflects
      the threads I followed in a 50-year journey of research in the complex tapestry
      of bioenergetics and various aspects of microbial metabolism. An early interest
      in biochemical and microbial evolution led to the fertile hunting grounds of
      anoxygenic photosynthetic bacteria. Viewed as a physiological class, these
      organisms show remarkable metabolic versatility in that certain individual
      species are capable of using all the known major types of energy conversion
      (photosynthetic, respiratory, and fermentative) to support growth. Since such
      anoxyphototrophs are readily amenable to molecular genetic/biological
      manipulation, it can be expected that they will eventually provide important
      clues for unraveling the evolutionary relationships of the several kinds of
      energy conversion. I gradually came to believe that understanding the evolution
      of phototrophs would require detailed knowledge not only of how light is
      converted to chemical energy, but also of a) pathways of monomer production from
      extracellular sources of carbon and nitrogen and b) mechanisms cells use for
      integrating ATP regeneration with the energy-requiring biosyntheses of biological
      macromolecules. Serendipic observation of photoproduction of H2 from organic
      compounds by Rhodospirillum rubrum in 1949 led to discovery of N2 fixation by
      anoxyphototrophs, and this capacity was later exploited for the isolation of
      hitherto unknown species of photosynthetic prokaryotes, including the
      heliobacteria. Recent studies on the reaction centers of the heliobacteria
      suggest the possibility that these bacteria are descendents of early phototrophs
      that gave rise to oxygenic photosynthetic organisms. 

PMID- 24311285
TI  - Selective disruption of energy flow from phycobilisomes to Photosystem I.
AB  - Efficient production of ATP and NADPH by the 'light' reactions of oxygen-evolving
      photosynthesis demands continuous adjustment of transfer of absorbed light energy
      from antenna complexes to Photosystem I (PS I) and II (PS II) reaction center
      complexes in response to changes in light quality. Treatment of intact
      cyanobacterial cells with N-ethylmaleimide appears to disrupt energy transfer
      from phycobilisomes to Photosystem I (PS I). Energy transfer from phycobilisomes
      to Photosystem II (PS II) is unperturbed. Spectroscopic analysis indicates that
      the individual complexes (phycobilisomes, PS II, PS I) remain functionally intact
      under these conditions. The results are consistent with the presence of
      connections between phycobiliproteins and both PS II and PS I, but they do not
      support the existence of direct contacts between the two photosystems. 

PMID- 24311286
TI  - Determination of the light pathlength elongation in leaves by measuring P700
      quantitatively.
AB  - P700 absorption change signals were measured at 800 nm for plant leaves and plant
      leaf extracts by illuminating with far-red light. The ratio of the signal
      amplitudes for the two sample types shows the degree of optical signal
      intensification. The intensification is due to optical path-length elongation,
      itself caused by scattering. The intensification was found to be between 6 and 15
      for different leaves. For spinach leaves, the intensification varied less than
      10% among samples. By replacing the air in the spongy layer of a leaf with an
      isotonic solution it was shown that nearly half of the intensification is due to
      the scattering at air-tissue interfaces. The comparison of the P700 signals of a
      leaf with its extract would seem to be a new technique for determining the
      optical scattering effects of leaves. 

PMID- 24311284
TI  - The biosynthesis of bacterial and plastidic c-type cytochromes.
AB  - The biosynthesis of bacterial and plastidic c-type cytochromes includes several
      steps that occur post-translationally. In the case of bacterial cytochromes, the
      cytosolically synthesized pre-proteins are translocated across the cytoplasmic
      membrane, the pre-proteins are cleaved to their mature forms and heme is ligated
      to the processed apoprotein. Although heme attachment has not been studied
      extensively at the biochemical level, molecular genetic approaches suggest that
      the reaction generally occurs after translocation of the apoprotein to the
      periplasm. Recent studies with Bradyrhizobium japonicum and Rhodobacter
      capsulatus indicate that the process of heme attachment requires the function of
      a large number of genes. Mutation of these genes generates a pleiotropic
      deficiency in all c-type cytochromes, suggesting that the gene products
      participate in processes required for the biosynthesis of all c-type cytochromes.
      In eukaryotic cells, the biosynthesis of photosynthetic c-type cytochromes is
      somewhat more complex owing to the additional level of compartmentation.
      Nevertheless, the basic features of the pathway appear to be conserved. For
      instance, as is the case in bacteria, translocation and processing of the pre
      proteins is not dependent on heme attachment. Genetic analysis suggests that the
      nuclear as well as the plastid genomes encode functions required for heme
      attachment, and that these genes function in the biosynthesis of the membrane
      associated as well as the soluble c-type cytochrome of chloroplasts. A feature of
      cytochromes c biogenesis that appears to be conserved between chloroplasts and
      mitochondria is the sub-cellular location of the heme attachment reaction (p-side
      of the energy transducing membrane). Continued investigation of all three
      experimental systems (bacteria, chloroplasts, mitochondria) is likely to lead to
      a greater understanding of the biochemistry of cytochrome maturation as well as
      the more general problem of cofactor-protein association during the assembly of
      an energy transducing membrane. 

PMID- 24311287
TI  - Spectroscopy of non-photochemical and photochemical quenching of chlorophyll
      fluorescence in leaves; evidence for a role of the light harvesting complex of
      Photosystem II in the regulation of energy dissipation.
AB  - Dissipation of absorbed excitation energy as heat, measured by its effect on the
      quenching of chlorophyll fluorescence, is induced under conditions of excess
      light in order to protect the photosynthetic apparatus of plants from light
      dependent damage. The spectral characteristics of this quenching have been
      compared to that due to photochemistry in the Photosystem II reaction centre
      using leaves of Guzmania monostachia. This was achieved by making measurements at
      77K when fluorescence emission bands from each type of chlorophyll protein
      complex can be distinguished. It was demonstrated that photochemistry and non
      photochemical dissipation preferentially quench different emission bands and
      therefore occur by dissimilar mechanisms at separate sites. It was found that
      photochemistry was associated with a preferential quenching of emission at 688 nm
      whereas the spectrum for rapidly reversible non-photochemical quenching had
      maxima at 683 nm and 698 nm, suggesting selective quenching of the bands
      originating from the light harvesting complexes of Photosystem II. Further
      evidence that this was occurring in the light harvesting system was obtained from
      the fluorescence excitation spectra recorded in the quenched and relaxed states. 

PMID- 24311288
TI  - Generation and quenching of singlet molecular oxygen by aggregated
      bacteriochlorophyll d in model systems and chlorosomes.
AB  - Both photogeneration and quenching of singlet oxygen by monomeric and aggregated
      (dimeric and oligomeric) molecules of bacteriochlorophyll (BChl) d have been
      studied in solution and in chlorosomes isolated from the green photosynthetic
      bacterium Chlorobium vibrioforme f. thiosulfatophilum. The yield of singlet
      oxygen photogeneration by pigment dimers was about 6 times less than for
      monomers. Singlet oxygen formation was not observed in oligomer-containing
      solutions or in chlorosomes. To estimate the efficiency of singlet oxygen
      quenching an effective rate constant for (1)O2 quenching by BChl molecules (kq
      (M)) was determined using the Stern-Volmer equation and the total concentration
      of BChl d in the samples. In solutions containing only monomeric BChl, the kq (M)
      values coincide with the real values for (1)O2 quenching rate constants by BChl
      molecules. Aggregation weakly influenced the kq (M) values in pigment solutions.
      In chlorosomes (which contain both BChl and carotenoids) the kq (M) value was
      less than in solutions of BChl alone and much less than in acetone extracts from
      chlorosomes. Thus (1)O2 quenching by BChl and carotenoids is much less efficient
      in chlorosomes than in solution and is likely caused primarily by BChl molecules
      which are close to the surface of the large chlorosome particles. The data allow
      a general conclusion that monomeric and dimeric chlorophyll molecules are the
      most likely sources of (1)O2 formation in photosynthetic systems and excitation
      energy trapping by the long wavelength aggregates as well as (1)O2 physical
      quenching by monomeric and aggregated chlorophyll can be considered as parts of
      the protective system against singlet oxygen formation. 

PMID- 24311289
TI  - The kinetics of reactions around the cytochrome bf complex studied in an isolated
      system.
AB  - The kinetics of oxidation and reduction of P700, plastocyanin, cytochrome f and
      cytochrome b-563 were studied in a reconstituted system consisting of Photosystem
      I particles, cytochrome bf complex and plastocyanin, all derived from pea leaf
      chloroplasts. Decyl plastoquinol was the reductant of the bf complex. Turnovers
      of the system were initiated by laser flashes. The reaction between oxidised P700
      and plastocyanin was non-homogeneous in that a second-order rate coefficient of
      c. 5*10(-7) M(-1) s(-1) applied to 80% of the P700(+) and c. 0.7*10(7) M(-1) s(
      1) to the remainder. In the presence of bf complex, but without quinol, the
      electron transfer between cytochrome f and oxidised plastocyanin could be
      described by a second-order rate coefficient of c. 4*10(7) M(-1) s(-1) (forward),
      and c. 1.6*10(7) M(-1) s(-1) (reverse). The equilibrium coefficient was thus 2.5.
      Unexpectedly, there was little reduction of cytochrome f (+) or plastocyanin(+)
      by electrons from the Rieske centre. With added quinol, reduction of cytochrome b
      563 occurred. Concomitantly, electrons appeared in the oxidised species. It was
      inferred that either the Rieske centre was not involved in the high-potential
      chain of electron transfer events, or that, only in the presence of quinol,
      electrons were quickly passed from the Rieske centre to cytochrome f (+).
      Additionally, the presence of quinol altered the equilibrium coefficient for the
      cyt f/PC interaction from 2.5 to c. 5. The reaction between quinol and the bf
      complex was describable by a second-order rate coefficient of about 3*10(6) M(-1)
      s(-1). The pattern of the redox reactions around the bf complex could be
      simulated in detail with a Q-cycle model as previously found for chloroplasts. 

PMID- 24311290
TI  - Protein thiol oxidation does not change in skeletal muscles of aging female mice.
AB  - Oxidative stress caused by reactive oxygen species is proposed to cause age
      related muscle wasting (sarcopenia). Reversible oxidation of protein thiols by
      reactive oxygen species can affect protein function, so we evaluated whether
      muscle wasting in normal aging was associated with a pervasive increase in
      reversible oxidation of protein thiols or with an increase in irreversible
      oxidative damage to macromolecules. In gastrocnemius muscles of C57BL/6J female
      mice aged 3, 15, 24, 27, and 29 months there was no age related increase in
      protein thiol oxidation. In contrast, there was a significant correlation (R (2)
      = 0.698) between increasing protein carbonylation, a measure of irreversible
      oxidative damage to proteins, and loss of mass of gastrocnemius muscles in aging
      female mice. In addition, there was an age-related increase in lipofuscin
      content, an aggregate of oxidised proteins and lipids, in quadriceps limb muscles
      in aging female mice. However, there was no evidence of an age-related increase
      in malondialdehyde or F2-isoprostanes levels, which are measures of oxidative
      damage to lipids, in gastrocnemius muscles. In summary, this study does not
      support the hypothesis that a pervasive increase in protein thiol oxidation is a
      contributing factor to sarcopenia. Instead, the data are consistent with an aging
      theory which proposes that molecular damage to macromolecules leads to the
      structural and functional disorders associated with aging. 

PMID- 24311291
TI  - A mechanistic study of the spontaneous hydrolysis of glycylserine as the simplest
      model for protein self-cleavage.
AB  - A common feature of several classes of intrinsically reactive proteins with
      diverse biological functions is that they undergo self-catalyzed reactions
      initiated by an N->O or N->S acyl shift of a peptide bond adjacent to a serine,
      threonine, or cysteine residue. In this study, we examine the N->O acyl shift
      initiated peptide-bond hydrolysis at the serine residue on a model compound,
      glycylserine (GlySer), by means of DFT and ab initio methods. In the most
      favorable rate-determining transition state, the serine ?COO(-) group acts as a
      general base to accept a proton from the attacking ?OH function, which results in
      oxyoxazolidine ring closure. The calculated activation energy (29.4 kcal mol(-1)
      ) is in excellent agreement with the experimental value, 29.4 kcal mol(-1) ,
      determined by (1) H NMR measurements. A reaction mechanism for the entire process
      of GlySer dipeptide hydrolysis is also proposed. In the case of proteins, we
      found that when no other groups that may act as a general base are available, the
      N->O acyl shift mechanism might instead involve a water-assisted proton transfer
      from the attacking serine ?OH group to the amide oxygen. However, the calculated
      energy barrier for this process is relatively high (33.6 kcal mol(-1) ), thus
      indicating that in absence of catalytic factors the peptide bond adjacent to
      serine is no longer a weak point in the protein backbone. An analogous
      rearrangement involving the amide N-protonated form, rather than the principle
      zwitterion form of GlySer, was also considered as a model for the previously
      proposed mechanism of sea-urchin sperm protein, enterokinase, and agrin (SEA)
      domain autoproteolysis. The calculated activation energy (14.3 kcal mol(-1) ) is
      significantly lower than the experimental value reported for SEA (~21 kcal mol(
      1) ), but is still in better agreement as compared to earlier theoretical
      attempts.

PMID- 24311292
TI  - Functional characterization of zebrafish K2P18.1 (TRESK) two-pore-domain K+
      channels.
AB  - The human KCNK18 gene is predominantly expressed in brain, spinal cord, and
      dorsal root ganglion neurons. Encoded K2P18.1K(+) channels are functionally
      implicated in migraine, pain and anesthesia. Data delineating the in vivo
      significance of K2P18.1 are still limited owing to a lack of model systems
      allowing for rapid, whole organism phenotypic analyses. We hypothesized that
      zebrafish (Danio rerio) might close this scientific gap. This work was designed
      to characterize the zebrafish ortholog of K2P18.1 in comparison to human K2P18.1
      channels. The complete coding sequence of zKCNK18 was amplified from zebrafish
      cDNA. Zebrafish KCNK18 expression was assessed by in situ hybridization. Human
      and zebrafish K2P18.1 currents were functionally analyzed using two-electrode
      voltage clamp electrophysiology and the Xenopus oocyte expression system. KCNK18
      mRNA is expressed in zebrafish brain and eyes. Human and zebrafish K2P18.1
      proteins share 32 % identity. Zebrafish K2P18.1 channels mediate K(+)-selective
      background currents that stabilize the negative resting membrane potential.
      Functional similarities between human and zK2P18.1 currents include open
      rectification properties, inhibition by barium, and regulation by signaling
      molecules protein kinase (PK)C, PKA, and phospholipase C. In contrast to the
      human ortholog, zK2P18.1 exhibited reduced sensitivity to elevation of
      intracellular calcium levels by ionomycin and was virtually insensitive to
      inhibition by quinidine. Zebrafish and human K2P18.1 channels share functional
      and regulatory properties, indicating that the zebrafish may serve as model to
      assess K2P18.1 function in vivo. However, distinct differences in K2P18.1 current
      regulation require careful consideration when zebrafish data are extrapolated to
      human physiology. 

PMID- 24311293
TI  - Natriuretic peptide receptors and heart failure: to B or not to B blocked?

PMID- 24311294
TI  - Laparoscopic division of a portosystemic shunt for recurrent life-threatening
      rectal variceal bleeding: report of a case.
AB  - In patients with severe portal hypertension related to liver cirrhosis,
      recanalization of umbilical veins may lead to both development and rupture of
      massive anorectal varices. In this setting, while transjugular intrahepatic
      portosystemic shunt (TIPS) is considered as the treatment of choice, the
      management of these patients remains unclear in case of contraindications to
      TIPS. Laparoscopic division of massive portosystemic shunts has been reported to
      yield beneficial effects in patients with isolated hepatic encephalopathy but has
      never been attempted in a context of life-threatening lower gastrointestinal
      bleeding. In the present case report, we both describe the operative technique of
      laparoscopic division of recanalized umbilical veins to treat recurrent massive
      haemorrhage following rupture of giant rectal varices in a 68-year-old Child C
      cirrhotic patient contraindicated to TIPS and report the postoperative course of
      the patient. 

PMID- 24311295
TI  - Metal-free reductive cleavage of C-N and S-N bonds by photoactivated electron
      transfer from a neutral organic donor.
AB  - A photoactivated neutral organic super electron donor cleaves challenging
      arenesulfonamides derived from dialkylamines at room temperature. It also cleaves
      a) ArC?NR and b) ArN?C bonds. This study also highlights the assistance given to
      these cleavage reactions by the groups attached to N in (a) and to C in (b), by
      lowering LUMO energies and by stabilizing the products of fragmentation. 

PMID- 24311296
TI  - A prospective evaluation of Dignity Therapy in advanced cancer patients admitted
      to palliative care.
AB  - BACKGROUND: Dignity Therapy is a brief, psychosocial intervention for patients
      with incurable disease. AIM: To investigate participation in and evaluation of
      Dignity Therapy and longitudinal changes in patient-rated outcomes. DESIGN: A
      prospective (pre/post) evaluation design was employed. Evaluation questionnaires
      were completed when patients received the generativity document (T1) and 2 weeks
      later (T2). Changes from baseline (T0) were measured in sense of dignity,
      Structured Interview for Symptoms and Concerns items, Patient Dignity Inventory,
      Hospital Anxiety and Depression Scale and European Organisation for Research and
      Treatment of Cancer QLQ-C15-PAL (ClinicalTrials.gov number: NCT01507571).
      SETTING/PARTICIPANTS: Consecutive patients with incurable cancer, >=18 years,
      informed of prognosis and not having cognitive impairment/physical limitations
      precluding participation were included at a hospice and a hospital palliative
      medicine unit. RESULTS: Over 2 years, 80 of 341 eligible patients completed
      Dignity Therapy. At T1, 55 patients completed evaluations, of whom 73%-89% found
      Dignity Therapy helpful, satisfactory and of help to relatives; 47%-56% reported
      that it heightened their sense of purpose, dignity and will to live. Quality of
      life decreased (mean = -9 (95% confidence interval: -14.54; -2.49)) and
      depression increased (mean = 0.31 (0.06; 0.57)) on one of several depression
      measures. At T2 (n = 31), sense of dignity (mean = -0.52 (-1.01; -0.02)) and
      sense of being a burden to others (mean = -0.26 (-0.49; -0.02)) improved.
      Patients with children and lower performance status, emotional functioning and
      quality of life were more likely to report benefit. CONCLUSIONS: This study adds
      to the growing body of evidence supporting Dignity Therapy as a valuable
      intervention in palliative care; a substantial subset of patients facing end of
      life found it manageable, relevant and beneficial.

PMID- 24311297
TI  - Somatic and germ-line mosaicism of deletion 15q11.2-q13 in a mother of dyzigotic
      twins with Angelman syndrome.
AB  - Angelman syndrome (AS, OMIM105830) is a neurogenetic disorder caused by different
      genetic mechanisms. Determining the genetic mechanism is essential to establish
      the recurrence risk and the accuracy of genetic/reproductive counseling. The
      majority of AS patients present with a deletion of the 15q11.2-q13 region on the
      maternally derived chromosome. The other genetic mechanisms are: paternal disomy
      of chromosome 15, imprinting center defects, and mutations in the ubiquitin
      protein ligase E3A gene (UBE3A). Different recurrence risks are associated with
      each specific genetic mechanism involved. We report on the study of dizygotic
      twins with classic phenotypic AS due to deletion of the same maternally derived
      chromosome 15. The mother presented with hypopigmented macular lesions on the
      inner side of both arms. Fibroblast culture studies of the maternal hypopigmented
      skin areas from both arms showed mosaicism for a normal cell line and for a
      second cell line with a 15q11.2-q13 deletion. This family represents the first
      demonstrated case of maternal somatic and germ line mosaicism for 15q11.2-q13
      deletion as the cause of AS.

PMID- 24311298
TI  - How religion heals.

PMID- 24311299
TI  - Religion and mental health among blacks.
AB  - The positive role of religion in the mental health of black Americans is a much
      neglected theme in the literature. This paper considers "religion" as one of the
      important retained black cultural traits, which continues to play a vital role in
      the mental health and survival strategies of black Americans. The paper examines
      Grier and Cobbs's appraisal of the religion-mental health connection in black
      communities and identifies different ways for mental health practitioners to
      think about religious phenomena and the primal partnership between religion and
      mental health. The paper concludes with a challenge to keep awareness of the
      religion-mental health partnership together in the treatment of black Americans. 

PMID- 24311300
TI  - The body as theology in pastoral psychology.
AB  - The physical body is explored as a metaphor of transformation and healing in
      pastoral psychotherapy. Three sections of the paper outline 1) the perception of
      the body as a point of critical clinical intervention, 2) the understanding of
      body as a living image of soul, and 3) the body as corporal participant in the
      mystical Body of Christ. Primary concern focuses on correcting possible
      misperceptions (among both secular and pastoral "bodyists") of bodily dysfunction
      as retribution for sinful existence rather than, more biblically, as signaling an
      opportunity for the inrushing of healing, divine grace. A brief clinical example
      highlights some possible theoretical and methodological consequences of this
      clinical world view. 

PMID- 24311301
TI  - Religion and death: The clerical perspective.
AB  - This first descriptive report on the perspectives, experiences, and actions of
      clergy relative to terminal patients and their families details a highly
      emotionally charged complex of interactions. Some 276 clerics from fourteen
      different bodies provided information on their involvement in death-work,
      spiritual and personal resources, satisfactions and doubts, pastoral goals and
      purposes, and their background and outlooks regarding their own demise.
      Implications of these findings are explored with respect to various forms and
      contents of training and experience. Psychological versus spiritual roles are of
      special significance in clergy-patient-family relationships. 

PMID- 24311302
TI  - Health and salvation as the ethical ideal.
AB  - Health and salvation are related terms, because each seeks the well-being of the
      whole person. When placed within the Judeo-Christian context, health as salvation
      can be defined as the highest good for the total human community. This good is
      denied to humanity through the unequal use of the world's resources, a fact
      underscored by the current energy crisis. Two questions must be answered: 1) Do
      we possess the scientific means to rectify this ethically unacceptable situation?
      2) Do we desire to implement the necessary steps to change, should they be found?

PMID- 24311303
TI  - The pastor as genetic counselor.
AB  - The pastor as pastoral counselor in the setting of the church can play an
      important role on a genetic team. This article explores the role the pastor plays
      in the definitive stage: delivery of information, educating, supporting, and
      counseling in human genetics. Problems that are encountered by team members,
      patients, and families, and dominant feelings that seem to exist in couples or
      individuals who discover that their children have a birth defect or that they
      themselve are carriers of a faulty gene are revealed and illustrated through
      clinical examples and interviews. Further suggestions are given on how a
      constructive team approach can help provide information regarding birth defects
      and how pastors can help and participate in this process. 

PMID- 24311304
TI  - A report on The National Council of Community Mental Health Centers.
AB  - The National Council of Community Health Centers represents a professional
      development of great interest to clergy. Because mental health centers
      collaborate with community agencies and systems, their interventions on behalf of
      community mental health provide an occasion to work toward common goals. Their
      policy of shared responsibility with community leaders and consumers provides a
      unique opportunity for a practical integration of religious systems and the
      public arena. A number of pastors and mental health trained clergy are actively
      participating in this common effort on behalf of the nation's mental health. 

PMID- 24311305
TI  - The influence of lithium on calcium homeostasis in older patients in daily
      clinical practice.
AB  - BACKGROUND: Lithium can influence calcium homeostasis resulting in changes in
      parathormone set point and renal calcium handling. The clinical significance of
      these changes in older patients is unknown. The objective of this study was to
      investigate the possible association between duration of lithium treatment and
      corrected calcium, parathormone and 24-h urinary calcium excretion in older
      psychiatric patients corrected for renal function and vitamin 25OH D and also to
      estimate the point prevalence of hypercalcemia and raised parathormone. METHODS:
      A cross-sectional study of psychiatric outpatients visiting a specialized
      facility for older patients treated with lithium was performed. Patients
      underwent a comprehensive assessment and blood and urine testing. Potential
      confounders of calcium homeostasis were recorded. On the basis of the duration of
      lithium treatment, patients were divided into four groups. RESULTS: One hundred
      eleven patients were included, mean age 75.2 years. There was no significant
      association between the duration of lithium treatment and corrected calcium,
      parathormone and 24-h urinary calcium excretion. The point prevalence of
      hypercalcemia was 2.7% and 47.8% for raised parathormone. There was an unexpected
      but significant negative association between the duration of lithium treatment
      and vitamin 25OH D, with 76.9% vitamin 25OH D deficiency (<50 nmol/L) in the
      group using lithium for more than 10 years. CONCLUSIONS: No association was found
      between duration of lithium treatment and calcium parameters in older psychiatric
      outpatients, but there was a high prevalence of raised parathormone and an
      unexpected negative association between duration of lithium treatment and 25OH D.

PMID- 24311306
TI  - Predicting the expression of recombinant monoclonal antibodies in Chinese hamster
      ovary cells based on sequence features of the CDR3 domain.
AB  - Despite the development of high-titer bioprocesses capable of producing >10 g L(
      1) of recombinant monoclonal antibody (MAb), some so called "difficult-to
      express" (DTE) MAbs only reach much lower process titers. For widely utilized
      "platform" processes the only discrete variable is the protein coding sequence of
      the recombinant product. However, there has been little systematic study to
      identify the sequence parameters that affect expression. This information is
      vital, as it would allow us to rationally design genetic sequence and engineering
      strategies for optimal bioprocessing. We have therefore developed a new
      computational tool that enables prediction of MAb titer in Chinese hamster ovary
      (CHO) cells based on the recombinant coding sequence of the expressed MAb. Model
      construction utilized a panel of MAbs, which following a 10-day fed-batch
      transient production process varied in titer 5.6-fold, allowing analysis of the
      sequence features that impact expression over a range of high and low MAb
      productivity. The model identified 18 light chain (LC)-specific sequence features
      within complementarity determining region 3 (CDR3) capable of predicting MAb
      titer with a root mean square error of 0.585 relative expression units.
      Furthermore, we identify that CDR3 variation influences the rate of LC-HC
      dimerization during MAb synthesis, which could be exploited to improve the
      production of DTE MAb variants via increasing the transfected LC:HC gene ratio.
      Taken together these data suggest that engineering intervention strategies to
      improve the expression of DTE recombinant products can be rationally implemented
      based on an identification of the sequence motifs that render a recombinant
      product DTE.

PMID- 24311307
TI  - Automation practices in large molecule bioanalysis: recommendations from group L5
      of the global bioanalytical consortium.
AB  - In recent years, the use of automated sample handling instrumentation has come to
      the forefront of bioanalytical analysis in order to ensure greater assay
      consistency and throughput. Since robotic systems are becoming part of everyday
      analytical procedures, the need for consistent guidance across the pharmaceutical
      industry has become increasingly important. Pre-existing regulations do not go
      into sufficient detail in regard to how to handle the use of robotic systems for
      use with analytical methods, especially large molecule bioanalysis. As a result,
      Global Bioanalytical Consortium (GBC) Group L5 has put forth specific
      recommendations for the validation, qualification, and use of robotic systems as
      part of large molecule bioanalytical analyses in the present white paper. The
      guidelines presented can be followed to ensure that there is a consistent,
      transparent methodology that will ensure that robotic systems can be effectively
      used and documented in a regulated bioanalytical laboratory setting. This will
      allow for consistent use of robotic sample handling instrumentation as part of
      large molecule bioanalysis across the globe. 

PMID- 24311308
TI  - Comparative proteomic profiling during ovarian development of the shrimp
      Metapenaeus ensis.
AB  - Two-dimensional electrophoresis and mass spectrometry were used to identify
      proteins that are differentially expressed during ovarian maturation in
      Metapenaeus ensis. 87 spots with consistently significant quantitative
      differences (>= 1.5-fold for vol%) among stage I, III and V ovaries were chosen
      for MS/MS analysis. 45 spots were significantly matched to known proteins in the
      database (Mascot score >40). Half of them were down-regulated, in contrast to 9
      out of 45 proteins that were up-regulated as ovarian maturation proceeded.
      Functionally, these identified proteins could be classified into five major
      groups, including cytoskeleton (11 %), metabolism (18 %), signal transduction (32
      %), gene expression (14 %) and immune response (7 %). Among the differentially
      expressed reproduction-related proteins, the mRNA expression level of cellular
      retinoic acid/retinol binding protein in M. ensis (MeCRABP) during ovarian
      maturation was further characterized by quantitative real-time PCR. It was down
      regulated during ovarian maturation. In situ hybridization further revealed that
      MeCRABP transcript was localized in ooplasm of previtellogenic oocytes but not in
      vitellogenic oocytes. These results demonstrate the application of proteomic
      analysis for identification of proteins involved in shrimp ovarian maturation and
      they provide new insights into ovarian development.

PMID- 24311311
TI  - ChemNetworks: a complex network analysis tool for chemical systems.
AB  - Many intermolecular chemical interactions persist across length and timescales
      and can be considered to form a "network" or "graph." Obvious examples include
      the hydrogen bond networks formed by polar solvents such as water or alcohols. In
      fact, there are many similarities between intermolecular chemical networks like
      those formed by hydrogen bonding and the complex and distributed networks found
      in computer science. Contemporary network analyses are able to dissect the
      complex local and global changes that occur within the network over multiple time
      and length scales. This work discusses the ChemNetworks software, whose purpose
      is to process Cartesian coordinates of chemical systems into a network/graph
      formalism and apply topological network analyses that include network
      neighborhood, the determination of geodesic paths, the degree census, direct
      structural searches, and the distribution of defect states of network. These
      properties can help to understand the network patterns and organization that may
      influence physical properties and chemical reactivity. The focus of ChemNetworks
      is to quantitatively describe intermolecular chemical networks of entire systems
      at both the local and global levels and as a function of time. The code is highly
      general, capable of converting a wide variety of systems into a chemical network
      formalism, including complex solutions, liquid interfaces, or even self
      assemblies.

PMID- 24311310
TI  - Evaluation of bioactivity of alkali- and heat-treated titanium using fluorescent
      mouse osteoblasts.
AB  - Stimulation of osteoblast proliferation and differentiation is important for the
      in vivo bone-bonding ability of biomaterials. Previous in vitro studies have used
      biochemical assays to analyze osteoblast-specific gene expression in cultured
      osteoblasts. In this study, we generated transgenic mice harboring a monomeric
      red fluorescent protein 1 transgene under the control of a 2.3-kb fragment of the
      Col1a1 promoter, which is active specifically in osteoblasts and osteocytes. We
      established a fluorescent primary osteoblast culture system to allow noninvasive
      observation of osteoblast proliferation and differentiation on opaque materials
      in vitro. We used this system to evaluate alkali- and heat-treated titanium,
      which has a strong bone-bonding ability in vivo, and we observed a rapid increase
      in fluorescence intensity and characteristic multifocal nodule formation. A cell
      proliferation assay and RT-PCR to examine osteoblast-specific gene expression
      showed increased osteoblast proliferation and differentiation consistent with the
      fluorescence observations. This mouse model allowed us to use fluorescence
      intensity to visualize and quantify in vivo newly formed bone around implanted
      materials in femurs. The use of these fluorescent osteoblasts is a promising
      method for simple screening of the bone-bonding ability of new materials. 

PMID- 24311309
TI  - MicroRNAs regulate bone metabolism.
AB  - Osteoporosis is caused by an unbalance between bone formation and bone
      resorption. Bone homeostasis is regulated by intricate mechanisms. Recently, a
      novel class of regulatory factors termed microRNAs (miRNAs) has been found to
      play a crucial role in cell cycle control, apoptosis and other cellular processes
      including metabolism and differentiation. Published data have shown that some
      miRNAs regulate bone homeostasis, including bone formation, resorption,
      remodeling, repair and bone-related disease, by regulating the expression of
      certain cytokines and transcription factors. This review highlights the current
      knowledge of miRNAs and their involvement in the regulation of bone formation,
      bone resorption and the pathways regulating the progression of osteoporosis.

PMID- 24311312
TI  - Airway malacia in children with achondroplasia.
AB  - This study was undertaken to assess the frequency of airway malacia in infants
      and young children with achondroplasia, a population well known to be at risk for
      a variety of respiratory problems. We also wished to evaluate what, if any,
      contribution airway malacia makes to the complex respiratory issues that may be
      present in those with achondroplasia. Retrospective chart review of all infants
      and young children with achondroplasia who were assessed through the Midwest
      Regional Bone Dysplasia Clinics from 1985 through 2012 (n = 236) was completed.
      Records of comprehensive clinical examinations, polysomnographic assessments, and
      airway visualization were reviewed and abstracted using a data collection form.
      Analyses were completed comparing the group with and those without evidence for
      airway malacia. Thirteen of 236 patients (5.5%) were found to have airway
      malacia. Most of those affected had lower airway involvement (9/13). The presence
      of airway malacia was correlated with an increased occurrence of obstructive
      sleep apnea as well as need for oxygen supplementation, airway surgeries and
      tracheostomy placement. Although estimates of the frequency of airway malacia in
      the general population are limited, its frequency in children with achondroplasia
      appears to be much higher than any published general population estimate. The
      presence of airway malacia appears to confound other breathing abnormalities in
      this population and results in the need for more invasive airway treatments.

PMID- 24311313
TI  - A simulated mucus layer protects Lactobacillus reuteri from the inhibitory
      effects of linoleic acid.
AB  - Lactobacillus reuteri is a commensal, beneficial gut microbe that colonises the
      intestinal mucus layer, where it makes close contact with the human host and may
      significantly affect human health. Here, we investigated the capacity of linoleic
      acid (LA), the most common polyunsaturated fatty acid (PUFA) in a Western-style
      diet, to affect L. reuteri ATCC PTA 6475 prevalence and survival in a simulated
      mucus layer. Short-term (1 h) survival and mucin-agar adhesion assays of a log
      phase L. reuteri suspension in intestinal water demonstrated that the simulated
      mucus layer protected L. reuteri against the inhibitory effects of LA by lowering
      its contact with the bacterial cell membrane. The protective effect of the
      simulated mucus layer was further evaluated using a more complex and dynamic
      model of the colon microbiota (SHIME(r)), in which L. reuteri survival was
      monitored during 6 days of daily exposure to LA in the absence (L-SHIME) and
      presence (M-SHIME) of a simulated mucus layer. After 6 days, luminal L- and M
      SHIME L. reuteri plate counts had decreased by 3.1+/-0.5 and 2.6+/-0.9 log
      cfu/ml, respectively. Upon supplementation of 1.0 g/l LA, the decline in the
      luminal L. reuteri population started earlier than was observed for the control.
      In contrast, mucin-agar levels of L. reuteri (in the M-SHIME) remained unaffected
      throughout the experiment even in the presence of high concentrations of LA.
      Overall, the results of this study indicate the importance of the mucus layer as
      a protective environment for beneficial gut microbes to escape from stress by
      high loads of the antimicrobial PUFA LA to the colon, i.e. due to a Western-style
      diet. 

PMID- 24311314
TI  - Probiotic supplement consumption alters cytokine production from peripheral blood
      mononuclear cells: a preliminary study using healthy individuals.
AB  - The objective of this study was to examine the effect of daily probiotic
      supplementation upon the immune profile of healthy participants by the assessment
      of ex vivo cytokine production. Twenty healthy adult volunteers received a multi
      strain probiotic supplement consisting of two strains of Lactobacillus
      acidophilus (CUL60 and CUL21), Bifidobacterium lactis (CUL34) and Bifidobacterium
      bifidum (CUL20) and fructooligosaccharide for 12 weeks. Blood samples were
      collected at baseline, 6 and 12 weeks. Peripheral blood mononuclear cells (PBMCs)
      were isolated and cultured ex vivo in the presence or absence of
      lipopolysaccharide and cytokine production was assessed. Postintervention, a
      significant decrease in the production of interleukin-6 and interleukin-1beta was
      apparent when PBMCs were incubated in the presence of lipopolysaccharide, whilst
      a significant increase in IL-10 and transforning growth factor-beta production
      was seen when the cells were incubated without an additional stimulus. This
      preliminary study demonstrates the potential of a multi-strain probiotic
      supplement to alter the immune response as demonstrated by changes in ex vivo
      cytokine production. Such results demonstrate the potential benefit of probiotic
      supplementation for healthy individuals and warrants further investigation. 

PMID- 24311315
TI  - The diversity of intestinal microbiota of Mongolians living in Inner Mongolia,
      China.
AB  - The Mongolian nationality has developed their unique lifestyle and dietary habit
      for thousands of years. However, by now, little research has been focused on
      Mongolian gut microbiota and how it is related to different dietary habits. In
      this study, denaturing gradient gel electrophoresis (DGGE) and quantitative
      polymerase chain reaction (qPCR) methods were applied to reveal the diversity of
      predominant gut bacteria of 48 healthy Mongolians recruited from Hohhot city and
      the Xilin Gol pasturing area in Inner Mongolia. Compared to similar studies of
      other nationalities, results from the present study have confirmed that the
      composition of Mongolian gut microbiota is highly similar at the phylum level
      (Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) but variable at
      the genus level. Especially, the numbers of Phascolarctobacterium, Lactobacillus
      and Bifidobacterium are rather high. DGGE profiles of Lactobacillus and
      Bifidobacterium revealed that Lactobacillus casei, Bifidobacterium longum and
      Bifidobacterium animalis subsp. lactis were predominant in the gut of the
      Mongolian subjects studied. On the contrary, Lactobacillus helveticus was
      detected in every pasturing area Mongolian, but not in any of the Hohhot city
      Mongolians. qPCR results revealed that the numbers of Lactobacillus and
      Bifidobacterium of Xilin Gol Mongolians were significantly higher (P<0.05) than
      that of Hohhot Mongolians, whereas the numbers of Enterobacterium were
      significantly lower (P<0.05). In addition, by partial least squares discriminate
      analysis and cluster analysis of data generated from DGGE and qPCR experiments, a
      striking difference in the composition of intestinal microbiota of Mongolians
      living in Hohhot city and the Xilin Gol pasturing area has been found. This study
      clearly shows that diet affects the microbiota composition of Mongolians living
      in different circumstances, i.e. urban versus rural. 

PMID- 24311316
TI  - Prevention and treatment of diarrhoea with Saccharomyces boulardii in children
      with acute lower respiratory tract infections.
AB  - The aim of this study was to determine whether Saccharomyces boulardii prevents
      and treats diarrhoea and antibiotic-associated diarrhoea (AAD) in children. A
      total of 333 hospitalised children with acute lower respiratory tract infection
      were enrolled in a 2-phase open randomised controlled trial. During the 1st
      phase, all children received intravenous antibiotics (AB). They were randomly
      allocated to group A (S. boulardii 500 mg/day + AB, n=167) or group B (AB alone,
      n=166) and followed for 2 weeks. Diarrhoea was defined as >=3 loose/watery
      stools/day during at least 2 days, occurring during treatment and/or up to 2
      weeks after AB therapy had stopped. AAD was considered when diarrhoea was caused
      by Clostridium difficile or when stool cultures remained negative. In the 2nd
      phase of the study, group B patients who developed diarrhoea were randomly
      allocated to two sub-groups: group B1 (S. boulardii + oral rehydration solution
      (ORS)) and group B2 (ORS alone). Data from 283 patients were available for
      analysis. Diarrhoea prevalence was lower in group A than in group B (11/139
      (7.9%) vs. 42/144 (29.2%); relative risk (RR): 0.27, 95% confidence interval
      (CI): 0.1-0.5). S. boulardii reduced the risk of AAD (6/139 (4.3%) vs. 28/144
      (19.4%); RR: 0.22; 95% CI: 0.1-0.5). When group B patients developed diarrhoea
      (n=42), S. boulardii treatment during 5 days (group B1) resulted in lower stool
      frequency (P<0.05) and higher recovery rate (91.3% in group B1 vs. 21.1% in B2;
      P<0.001). The mean duration of diarrhoea in group B1 was shorter (2.31+/-0.95 vs.
      8.97+/-1.07 days; P<0.001). No adverse effects related to S. boulardii were
      observed. S. boulardii appeared to be effective in the prevention and treatment
      of diarrhoea and AAD in children treated with intravenous antibiotics.

PMID- 24311317
TI  - Effects of age and controlled oral dosing of Enterococcus faecium on epithelial
      properties in the piglet small intestine.
AB  - Enterococcus faecium NCIMB 10415 is a licensed probiotic for piglets that has
      been shown to positively affect diarrhoea incidence and to act on transport
      properties and immunological parameters in the porcine intestine. The aim of the
      present study was to examine its effects on jejunal absorptive and secretory
      capacities around weaning. Furthermore, the possible involvement of heat shock
      proteins in the effects of probiotics on epithelial functions was investigated. A
      significant part of the probiotic was dosed orally to reduce the variability of
      intake of the probiotic. The piglets were randomly assigned to a control and a
      probiotic feeding group, the latter receiving 4.5*109 cfu/day of E. faecium
      directly into the mouth for 34 days starting after birth. Additionally, their
      feed was supplemented with the probiotic strain. Piglets were weaned at day 29
      after birth. Ussing chamber studies were conducted with the mid-jejunum of
      piglets aged 14, 28, 31, 35 and 56 days. Changes in short-circuit current
      (DeltaIsc) were measured after stimulation of Na+-coupled absorption with L
      glutamine or glucose or with the secretagogue prostaglandin E2 (PGE2). The mRNA
      expression for SGLT1, CFTR and various heat shock proteins was determined. The
      transport properties changed significantly with age. The glucose-, L-glutamine-
      and PGE2-induced changes in Isc were highest at day 31 after birth. No
      significant differences between the feeding groups were observed. The mRNA of
      HSP60, HSC70, HSP70 and HSP90 was expressed in the jejunal tissues. The mRNA
      expression of HSC70 was higher and that of HSP60 was lower in the probiotic
      group. HSC70 expression increased with age. In conclusion, whereas age effects
      were observed on absorptive and secretory functions, controlled E. faecium dosing
      had no measurable effects on these functional parameters in this experimental
      setup. The possible role of heat shock proteins should be further evaluated. 

PMID- 24311318
TI  - Individual responses of mother sows to a probiotic Enterococcus faecium strain
      lead to different microbiota composition in their offspring.
AB  - Pregnant gilts were fed the probiotic Enterococcus faecium NCIMB10415 (SF68) one
      month before birth of piglets. DNA extracts of sow faeces taken in weekly
      intervals as well as extracts from the intestine of their offspring during the
      suckling period at 12 and 26 days of life were analysed by denaturing gradient
      gel electrophoresis (DGGE) and quantitative PCR. DGGE profiles of faecal
      bacterial communities from three out of six probiotic-fed sows were distinctly
      different from the control and other probiotic-fed sows at all time points after
      probiotic supplementation. The probiotic-fed sows and their offspring were
      therefore divided into non-responder (n=3) and responder (n=3) groups. The
      probiotic strain significantly increased faecal lactobacilli cell numbers in
      mother sows, which could be assigned to a significant increase of Lactobacillus
      amylovorus and Lactobacillus acidophilus. Responding sows showed a more
      pronounced increase than non-responding sows. Similarly, suckling piglets from
      non-responding and responding sows showed numeric and significant differences for
      different bacterial groups and species. DGGE profiles of suckling piglets from
      responding sows also grouped more closely than profiles from control animals. Non
      metric multiscaling of suckling piglets showed the same tendency for suckling
      piglets, but not for post-weaning piglets. This study showed that the probiotic
      E. faecium strain modified the faecal microbiota of sows. This modification is
      carried over to their offspring, but leads to changes that do not mirror the
      quantitative composition in the mother sow. Individual variations in the
      bacterial composition of mother sows before probiotic feed intake may influence
      the impact of a probiotic in sows and their offspring. 

PMID- 24311319
TI  - Increased expression of clp genes in Lactobacillus delbrueckii UFV H2b20 exposed
      to acid stress and bile salts.
AB  - The ability to survive in harsh environments is an important criterion to select
      potential probiotics strains. The objective of this study was to identify and
      carry out phylogenetic and expression analysis by quantitative real-time PCR of
      the clpP, clpE, clpL and clpX genes in the probiotic strain Lactobacillus
      delbrueckii UFV H2b20 exposed to the conditions prevailing in the
      gastrointestinal tract (GIT). Phylogenetic trees reconstructed by Bayesian
      inference showed that the L. delbrueckii UFV H2b20 clpP, clpL and clpE genes and
      the ones from L. delbrueckii ATCC 11842 were grouped. The exposure of cells to
      MRS broth of pH 3.5 for 30 and 60 min resulted in an increased expression of the
      four genes. Exposure of the L. delbrueckii UFV H2b20 cells for 30 and 60 min to
      MRS broth containing 0.1% bile salts increased the expression of the clpP and
      clpE genes, while the expression level of the clpL and clpX genes increased only
      after 30 min of exposure. The involvement of the studied genes in the responses
      to acid stress and bile salts suggests a possible central role of these genes in
      the survival of L. delbrueckii UFV H2b20 during the passage through the GIT, a
      characteristic necessary for probiotic strains. 

PMID- 24311320
TI  - Isolation and structural identification of glycopolymers of Bifidobacterium
      bifidum BIM B-733D as putative players in pathogenesis of autoimmune thyroid
      diseases.
AB  - Bifidobacterium bifidum 791 (commercially available as B. bifidum BIM B-733D)
      cell-surface biopolymers (BPs) interact selectively with human serum thyroid
      peroxidase (TPO) and thyroglobulin (Tg) autoantibodies (anti TPO and anti Tg,
      respectively). BPanti-TPO and BPanti-Tg were isolated from the soluble fraction
      of B. bifidum BIM B-733D by affinity chromatography with anti-TPO or anti-Tg,
      respectively. Homogeneity of affinity eluates (AEanti-TPO and AEanti-Tg) was
      tested by size exclusion chromatography. For each AE, the elution profiles
      generated on the basis of absorbance at 280 nm do not conform to ELISA data for
      functional activity characteristic of BPs. Moreover, high functional activity was
      detected in chromatographic fractions that had significantly different molecular
      weights and no absorbance at 280 nm, which suggests a non-protein (carbohydrate)
      nature of BPanti-TPO and BPanti-Tg. The semi-preparative size exclusion
      chromatography of AEanti-TPO and AEanti-Tg with detection by refractometer gave
      5,000-7,000 Da fractions containing substances that interact selectively with
      either anti TPO (BPanti-TPO) or anti-Tg (BPanti-Tg) according to ELISA data.
      Analysis by two-dimensional NMR spectroscopy including a 1H, 13C-heteronuclear
      single-quantum coherence experiment indicated that both substances are linear
      alpha-1,6-glucans. For the first time, an immunological similarity (molecular
      mimicry) of glycopolymers of B. bifidum BIM B-733D and human thyroid proteins,
      TPO and Tg, was shown. On the whole, our data point to a possible role of
      bifidobacteria in the pathogenesis of autoimmune thyroid diseases (ATD). The main
      requirements for triggering/acceleration or prevention/abrogation of ATD by
      bifidobacteria through molecular mimicry mechanism are hypothesised to be (1)
      genetic predisposition to ATD and (2) intestinal epithelium penetration by alpha
      1,6-glucan. 

PMID- 24311321
TI  - Interionic interactions in conducting nanoconfinement.
AB  - Interionic interactions in conducting nanopores determine how counterions may be
      packed in the pores subject to the applied voltage. In ideal metals, interactions
      are exponentially screened by metallic electrons. However, modern nanoporous
      electrodes are predominantly made of carbon materials. To what extent is this
      screening affected by a different mode of dielectric response in such materials?
      To answer this question we study Coulomb interaction of charges in cylindrical
      and slit pores that allow finite electric field penetration into the pore walls,
      as well as the Coulomb interaction in a nanogap between two thin walls of
      graphene modeled by a non-local dielectric function. In all cases studied the
      screening was found to be subtly different than in metallic nanopores, but still
      strong enough to support realization of the so called superionic state in such
      pores. 

PMID- 24311328
TI  - Insect antifeedant properties of anthranoids from the genusVismia.
AB  - Vismiones and ferruginins, representatives of a new class of lypophilic
      anthranoids from the genusVismia were found to inhibit feeding in larvae of
      species ofSpodoptera, Heliothis, and inLocusta migratoria. 

PMID- 24311329
TI  - Role of plant volatiles in resistance of selected rice varieties to brown
      planthopper,Nilaparvata lugens (Stal) (Homoptera: Delphacidae).
AB  - Rice plant volatiles extracted as steam distillates significantly affected the
      behavior and biology of the brown planthopper,Nilaparvata lugens (Stal). In a
      multichoice test, more females settled and fed on tillers of a susceptible rice
      variety "Taichung Native 1" (TN1), sprayed with its own extract or acetone than
      on TN1 tillers sprayed with the extract of the resistant variety "ARC6650" or
      "Ptb33." In another test,N. lugens females ingested significantly more of a 10%
      sucrose solution mixed with TN1 steam distillate extract than of plain sucrose
      solution or that mixed with extracts of resistant varieties. Topical application
      of the extracts of resistant varieties "Mudgo," "ASD7," "Rathu Heenati,"
      "Babawee," Ptb33, and ARC6650 caused significantly higher mortality of females
      than did the TN1 extract. Likewise, significantly more first-instar nymphs died
      when they were caged on susceptible TN1 plants sprayed with the extracts of
      resistant varieties than on plants sprayed with TN1 extract. The extract of 60
      day-old resistant plants was more toxic than the extract of 30-, 45-, or 100-day
      old plants. However, toxicity of the extract from susceptible TN1 remained low at
      all plant growth stages. 

PMID- 24311330
TI  - Compared behavioral responses of maleDrosophila melanogaster (Canton S) to
      natural and synthetic aphrodisiacs.
AB  - Cuticular aphrodisiacs fromD. melanogaster females were further characterized and
      the male response specificity towards such natural and synthetic unsaturated
      hydrocarbons was investigated. The behavioral activity seems to be correlated
      with some chain-length requirement and double-bond position; at least one double
      bond in position 7 seems necessary. This position is more abundant among natural
      monoenes, and among dienes which also bear a second double bond in position 11,
      whatever the chain length. Bioassays of the synthetic (Z,Z)-7,11-heptacosadiene
      yielded a dose-response curve close to that of the natural mixture of
      heptacosadienes in which the 7-11 isomer is predominant. This female specific
      7,11 heptacosadiene appears to be the most potent aphrodisiac for males of the
      species. Its threshold is lower than that of both 7,11-nonacosadiene and 7
      pentacosene which might also play a role in sex and species recognition. 

PMID- 24311331
TI  - Commercial hollow-fiber pheromone formulations: The degrading effect of sunlight
      on celcon fibers causing increased release rates of the active ingredient.
AB  - The effect of weathering on the release of pheromone analogs from Celcon fibers
      has been studied. Results from fibers exposed in Quebec indicate that UV
      radiation in sunlight degrades the Celcon, causing an increase in the release of
      the active materials. The results are discussed in the light of large interfiber
      release rate variation experienced with commercial fiber formulations, and the
      fact that the major use areas, to date, have been Arizona and California where
      the effect is likely to be much more pronounced. Stability of the release device
      to weathering is shown to be one of the many parameters to be considered in
      formulation design. 

PMID- 24311332
TI  - Attraction of moth species of Tortricidae, Gelechiidae, Geometridae, Drepanidae,
      Pyralidae, and Gracillariidae families to field traps baited with conjugated
      dienes.
AB  - Field surveys of a series of conjugated diunsaturated straight-chain primary
      alcohols, acetates, and aldehydes (dienes), including the 3,5-dode-cadienyl, 8,10
      dodecadienyl, 3,5-tetradecadienyl, 8,10-tetradecadienyl, 9,11-tetradecadienyl,
      and 10,12-tetradecadienyl primary alcohols, acetates, and most aldehydes, and the
      related monounsaturated straight-chain primary alcohols, acetates, and aldehydes
      (monoenes), including the 3-dodecadienyl alcohol and acetates, attracted the
      following species from the title families. Diene attractants have been
      demonstrated for at least onePhyllonorycter sp.,Chionodes lugubrella
      (Fabr.),Leptostales ferruminaria (Zell.),Drepana bilineata (Pack.),Pyrausta
      fodinalis (Led.),Notocelia purpurissatana Heinr.,Phaneta alterana Heinr. Monoene
      attractants were demonstrated forHedya separatana (Kft.),Cydia fletcherana
      (Kft.),Barbara mappana Free.,Ancylis burgessiana (Zell.),Ancylis nubeculana
      Clem.,Evippe prunifoliella Cham.,Phlyctaenia coronata tertialis (Gn.), aChionodes
      sp., a Gelechiidae sp., and an unidentifiedPhyllonorycter sp. Replicated field
      experiments showed attraction-inhibition relationships for most species.
      Electroantennagram data are presented forLeptostales ferruminaria andDrepana
      bilineata. 

PMID- 24311333
TI  - Determination of chirality of alcohol or latent alcohol semiochemicals in
      individual insects.
AB  - A method is described for determining the enantiomeric composition of chiral
      alcohols, lactones, and hydroxy acids in quantities ranging from 25 ng to 10 MUg.
      Derivatization of the substance with chirally pure acetyl lactate, followed by
      splitless capillary gas chromatography, enables enantiomeric determinations to be
      made within 1-3% of the actual value. This technique was applied in the
      determination of semiochemical inIps pini (Say),Apis mellifera (L.),
      andCryptolestes ferrugineus (Stephens). The results indicate that considerable
      variability exists within populations of some insects in the composition of their
      chiral semiochemicals, whereas others produce substances of constant composition.

PMID- 24311334
TI  - Genital sex pheromones of ixodid ticks: 1. Evidence of occurrence in anterior
      reproductive tract of American dog tick,Dermacentor variabilis (Say) (Acari:
      Ixodidae).
AB  - The occurrence of a genital sex pheromone in the anterior reproductive tract of
      partially fed femaleDermacentor variabilis was demonstrated by extraction and
      bioassay. A new type of bioassay, the "neutered" female assay, was developed to
      test the potency of extracts or chemically defined fractions to stimulate males
      to copulate. Electrophysiological tests confirmed the ability of males to detect
      the pheromone with sensilla on their cheliceral digits. Males of bothD.
      variabilis andD. andersoni exhibited neuronal excitation when stimulated with
      extracts of theD. variabilis reproductive tissues. The pheromone, which is
      soluble in methanol, was fractionated and found to contain at least two fractions
      that stimulated copulation by sexually excited males. Evidently, the pheromone is
      a mixture of two or more compounds. Histologic, ultrastructural, and
      histochemical studies suggest the vestibular vagina as the site of genital sex
      pheromone occurrence, presumably from secretions of the surrounding lobular
      accessory gland. The identity of the compounds that comprise the pheromone
      remains unknown. 

PMID- 24311335
TI  - Disturbance pheromones in the crayfishOrconectes virilis.
AB  - The reactions of individual crayfish to the introduction of waters from tanks
      containing other individuals were recorded to test for the release of chemicals
      by stressed crayfish. FemaleOrconectes virilis and maleO. rusticus did not show
      responses to stressed crayfish. MaleO. virilis responded differently to
      undisturbed and disturbed male crayfish (conspecific and heterospecific).
      Responses to waters from tanks which contained disturbed individuals were similar
      whether the source of disturbance was aggressive, predatory, or thermal.
      Chemical(s) involved appear to persist for at least one hour at room temperature.

PMID- 24311336
TI  - Isoflavonoid feeding deterrents forCostelytra zealandica Structure - Activity
      relationships.
AB  - A number of naturally occurring isoflavonoids of differing substitution patterns
      and oxidation states have been tested for feeding deterrent activity in a
      bioassay with larvae ofCostelytra zealandica White. The most active deterrents,
      which reduced feeding significantly at 0.2-1.0 MUg/g, are those compounds
      containing a ring B-fused cycloprenoid moiety. The least active compounds were
      highly oxidized coumestans and isoflavones. The ring B-fused cyclic isoprenoid
      moiety and the presence of a 2'-oxy function appear to be structural features
      important for high activity. It is suggested that the feeding deterrent activity
      of isoflavonoids relates to their stereochemistry and that the most active
      compounds have or can adopt a similar nonplanar molecular shape with a similar
      arrangement of polar and lipophilic groups. 

PMID- 24311337
TI  - Effect of gamma irradiation on allelopathic potential ofSorghum bicolor against
      weeds and nitrification.
AB  - The effect of low doses of gamma irradiation on the allelopathic potential
      ofSorghum bicolor against weeds and nitrification was investigated. The results
      revealed that all test doses (500, 1000 and 1500 rad) significantly increased the
      allelopathic activity of root exudates, aqueous extracts, and decaying residues
      aganst seed germination and seedling growth ofAmaranthus retroflexus. The results
      also indicated that all test doses stimulated the allelopathic potential of
      aqueous extracts and decaying residues against nitrification activity. The
      possible application of this approach in biological control is briefly discussed.

PMID- 24311338
TI  - cis-Vaccenyl acetate as an aggregation pheromone inDrosophila melanogaster.
AB  - Pentane extracts of matureDrosophila melanogaster males substantially increased
      the attractiveness of food odors to both males and females in a wind-tunnel
      olfactometer. Extracts of females caused no such increase. An active component of
      the extract was isolated and identified as (Z)-11-octadecenyl acetate (cis
      vaccenyl acetate, cVA), and synthetic cVA was active in bioassay. Hydrolysis of
      the ester linkage or movement of the double bond to the 9 position destroyed the
      activity. Mature virgin males released cVA into their feeding vials, and amounts
      of synthetic CVA equal to that released per male caused significant bioassay
      responses. Females, which were known to receive cVA from males during copulation,
      were found to emit relatively large amounts of the ester into their feeding vials
      within 6 hr after mating. cVA had been demonstrated previously to be a close
      range pheromone inD. melanogaster, discouraging males from courting other males
      or recently mated females; it now appears to have a longer-range function as
      well. 

PMID- 24311339
TI  - Gaster flagging by fire ants (Solenopsis spp.): Functional significance of venom
      dispersal behavior.
AB  - Behavioral and chemical studies with laboratory colonies indicate that the
      imported fire antSolenopsis invicta Buren (Myrmicinae) disperses venom through
      the air by raising and vibrating its gaster (i.e., "gaster flagging"). This
      mechanism of airborne venom dispersal is unreported for any ant species. Foraging
      workers utilize this air-dispersed venom (up to 500 ng) to repel heterospecifics
      encountered in the foraging arena, while brood tenders dispense smaller
      quantities (~ 1 ng) to the brood surface, presumably as an antibiotic. Brood
      tenders removed from the brood cell and tested in heteropspecific encounters in
      the foraging arena exhibited the complete repertoire of agonistic gaster flagging
      behavior. These observations suggest that airborne venom dispersal by workers is
      context specific rather than temporal caste specific and that workers can control
      the quantity of venom released. 

PMID- 24311340
TI  - The egg and the nucleus: a battle for supremacy (Nobel Lecture).

PMID- 24311341
TI  - Leaf mutants in diploid red clover (Trifolium pratense L.).
AB  - Leaf mutants were isolated and genetically stabilised in diploid red clover
      (Trifolium pratense). The major alteration showed normal trifoliolate leaves
      changed into multifoliolate leaves composed of 4-, 5-, 6- and 7 leaflets. As a
      result of recombination with other mutant alleles several genotypes were isolated
      with a different mode of leaf setting, different shapes and sizes of leaflets,
      variations in the whole plant habit, etc. A careful description was made of the
      mutant morphology and the development and genetic background was estimated as (h
      sl (2) ). The mutants demonstrated no disturbances in their generative
      reproduction and as a rule set seeds better than the standards. The primary
      evaluation permits a conclusion that the leaf alteration (complexity) is governed
      by at least three recessive pairs of alleles of additive action. The phenotypic
      expression of the altered leaves depends simply on the number of recessive
      alleles. Apart from the above there were some modifying genes of incomplete
      penetration. 

PMID- 24311342
TI  - Genetic analysis of bacterial blight resistance in seventy-four cultivars of
      rice, Oryza sativa L.
AB  - The genetics of resistance to bacterial blight, Xanthomonas oryzae (Uyeda and
      Ishiyama) Dowson, for 74 cultivars of rice, Oryza sativa L., was studied. The
      PX061 isolate of bacterial blight from the Philippines was used for inoculation
      of parental and hybrid populations. Single dominant genes at the Xa 4 locus
      convey resistance in 38 cultivars. Of these, 18 are resistant at all stages of
      plant growth and thus have the Xa 4 (a)allele for resistance. However, 20 are
      susceptible up to maximum tillering stage but are resistant at booting and
      flowering stages. These cultivars have the Xa 4 (b)allele for resistance. Thirty
      two cultivars have single recessive genes for resistance which are allelic to xa
      5.The resistance in 'DV85', 'DV86' and 'DZ78' is conditioned by two genes. At
      maximum tillering stage xa 5 conveys resistance. However, at later growth stages
      an additional dominant gene, designated Xa 7 in 'DZ78', also gives resistance.
      The dominant genes of 'DV85' and 'DV86' are probably allelic to Xa 7. Xa 7
      segregates independently of Xa 4, xa 5 and Xa 6, however like Xa 6, it conveys
      resistance at booting and post-booting stages only.The resistance in 'PI 231129'
      is conditioned by a single recessive gene, designated xa 8. It also segregates
      independently of Xa 4, xa 5 and Xa 6. 

PMID- 24311343
TI  - Paramutation at the sulfurea locus of Lycopersicon esculentum Mill. : VII.
      Determination of the time of occurrence of paramutation by the quantitative
      evaluation of the variegation.
AB  - 1. In tomato plants heterozygous for a mutant allele of the sulfurea (sulf) locus
      paramutation may take place: under the influence of a paramutant sulf allele, the
      paramutable wild type allele sulf (+), which is present in the same nucleus, is
      heritably altered with a definite frequency to a sulf mutant allele, either of
      the sulf (pura)or the sulf (vag)group. 2. A number of the sulf (+) sulf
      heterozygotes remain entirely green during their whole ontogenetic development
      (type I plants, without paramutation). However, others of the plants become
      variegated: these variegated plants contain-apart from green sectors - only
      yellow-green speckled sulf (vag)sectors (type II plants), or only pure yellow
      sulf (pura)sectors (type III plants) or both sulf (vag)and sulf (pura)sectors
      side by side (type IV plants). 3. For all variegated plants (types II, III and
      IV) we determined the sizes of the green and of the paramutant sulf (vag)and sulf
      (pura)sectors and made a statistical analysis of the values obtained. 4. We
      conducted observations over a period of three years and obtained following
      findings: type II plants (with sulf (vag)sectors) have an average size of the
      paramutant sectors of 27.9% (the whole plant being 100%). Type III plants (with
      sulf (pura)sectors) have an average sector's size of 25.7%, whereas the size of
      the paramutant sectors in type IV plants (with both sulf (vag)and sulf
      (pura)sectors) amounts to 54.4% (35.7% sulf (vag)and 18.7% sulf (pura)). Thus,
      the occurrence of tissues of both phenotypes in one plant has, on the average,
      been found to be correlated with a doubling of the proportion of paramutant
      sectors in that plant. 5. Within sulf (+) sulf heterozygotes there is, in
      general, a positive correlation between the frequency of paramutant plants and
      the proportion of paramutant sectors within the plants. This is mainly due to the
      fact that there is a significant positive correlation between the frequency of
      type IV plants and the frequency of paramutant plants, i.e. the more plants
      within a progeny variegated, the greater the frequency of type IV plants
      containing both sulf (vag)and sulf (pura)sectors. 6. These findings
      (mathematically analysed and compared with the consequences of several models)
      may result in the following concept: the paramutation processes in sulf (+) sulf
      heterozygotes are restricted to a small group of cells (16 cells at the most)
      during a short period of about three cell generations after seed germination and
      expansion of the cotyledons. In the course of which, the probability for the
      occurrence of paramutation decreases rather quickly from one cell generation to
      the next. These characteristics of paramutation processes mentioned cause the
      occurrence of rather large and well defined sectors of paramutant tissue. 

PMID- 24311344
TI  - Study on induced mutants resembling commercial varieties in bread wheat.
AB  - The occurrence of variants with phenotypic resemblance to the existing cultivated
      varieties of wheat, such as 'Sonalika', 'Arjun' and 'Kalyansona', evolved by
      hybridisation, has been found in various generations of the mutagen-treated
      populations of the variety 'Zaafrane'. The repetition and involvement of common
      genes in certain genotypes in the evolutionary history of these varieties is
      attributed to the induction of such intervarietal mutants.It is shown that
      selective reconstruction of a particular variety in bread wheat is not only
      possible, but also relatively easy, especially from a closely related variety.The
      study opens the possibility of utilising this method as a technique for
      developing components of a multiline. 

PMID- 24311345
TI  - Effectiveness of selection under different mating systems for the improvement of
      protein content in wheat (Triticum aestivum L. em Thell.).
AB  - The effectiveness of selection for the improvement of protein content under
      random intermating (recurrent selection) and selfing series (pedigree selection)
      was evaluated in a cross of winter and spring wheats, 'Atlas 66' * 'HD 1977'.
      Selection of 10 per cent high protein families resulted in an increase of 3.25
      per cent and 4.30 per cent of the mean of checks through pedigree and recurrent
      selection, respectively. The mean protein differences in both methods were not
      significant. The increase in protein content was accompanied by a decrease in the
      grains per spike, grain yield and 1000-kernel weight, and the decline was
      relatively higher in recurrently selected than pedigreed population. Since the
      pedigree method is simple, less time consuming, economically cheaper, has
      favourable shifts in association and better correlated responses, it was decided
      to follow a few cycles of pedigree selection in early segregating generations,
      after which one or two cycles of recurrent selection in the elite lines could be
      introduced to increase genetic variation and concentrate favourable genes for
      grain yield. 

PMID- 24311346
TI  - Restoration of pseudo-self-compatibility (PSC) in derivatives of a high-PSC * no
      PSC cross in Nemesia strumosa Benth.
AB  - Mean PSC increased following each generation of recurrent selection in F1, F2 and
      F3 Nemesia strumosa families derived from a cross of a 100% PSC plant to an
      unrelated 0% PSC plant. The first 100% PSC individuals occurred in the F4.
      Populations derived through sib pollination tended to have higher PSC means than
      lines derived through self pollination. One F3 family showed a three-fold higher
      PSC level when pollinated in the green-house than when pollinated in the growth
      chamber, while another F3 family similarly pollinated showed no change in PSC. 

PMID- 24311347
TI  - Comment on Zhu et al.: a meta-analysis of bisphosphonates for periprosthetic bone
      loss after total joint arthroplasty.

PMID- 24311348
TI  - Rational design of carboxyl groups perpendicularly attached to a graphene sheet:
      a platform for enhanced biosensing applications.
AB  - Graphene oxide (GO)-based materials offer great potential for
      biofunctionalization with applications ranging from biosensing to drug delivery.
      Such biofunctionalization utilizes specific functional groups, typically a
      carboxyl moiety, as anchoring points for biomolecule. However, due to the fact
      that the exact chemical structure of GO is still largely unknown and poorly
      defined (it was postulated to consist of various oxygen-containing groups, such
      as epoxy, hydroxyl, carboxyl, carbonyl, and peroxy in varying ratios), it is
      challenging to fabricate highly biofunctionalized GO surfaces. The predominant
      anchoring sites (i.e., carboxyl groups) are mainly present as terminal groups on
      the edges of GO sheets and thus account for only a fraction of the oxygen
      containing groups on GO. Herein, we suggest a direct solution to the long
      standing problem of limited abundance of carboxyl groups on GO; GO was first
      reduced to graphene and consequently modified with only carboxyl groups grafted
      perpendicularly to its surface by a rational synthesis using free-radical
      addition of isobutyronitrile with subsequent hydrolysis. Such grafted graphene
      oxide can contain a high amount of carboxyl groups for consequent
      biofunctionalization, at which the extent of grafting is limited only by the
      number of carbon atoms in the graphene plane; in contrast, the abundance of
      carboxyl groups on "classical" GO is limited by the amount of terminal carbon
      atoms. Such a graphene platform embedded with perpendicularly grafted carboxyl
      groups was characterized in detail by X-ray photoelectron spectroscopy, cyclic
      voltammetry, and electrochemical impedance spectroscopy, and its application was
      exemplified with single-nucleotide polymorphism detection. It was found that the
      removal of oxygen functionalities after the chemical reduction enhanced the
      electron-transfer rate of the graphene. More importantly, the introduction of
      carboxyl groups promoted a more efficient immobilization of DNA probes on the
      electrode surface and improved the performance of graphene as a biosensor in
      comparison to GO. The proposed material can be used as a universal platform for
      biomolecule immobilization to facilitate rapid and sensitive detection of DNA or
      proteins for point-of-care investigations. Such reactive carboxyl groups grafted
      perpendicularly on GO holds promise for a highly efficient tailored
      biofunctionalization for applications in biosensing or drug delivery. 

PMID- 24311350
TI  - Chauvinist's progress.

PMID- 24311349
TI  - Vortioxetine: first global approval.
AB  - Vortioxetine is an orally administered small molecule developed by Lundbeck A/S
      for the once-daily treatment of major depressive disorder (MDD) and generalized
      anxiety disorder (GAD). Vortioxetine received its first global approval for MDD
      in the USA in September 2013 and regulatory approval for its use in this
      indication in the EU (where it has received a positive opinion) and Canada is
      awaited. The drug is a bis-aryl-sulphanyl amine compound that combines serotonin
      (5-HT) reuptake inhibition with other characteristics, including receptor
      activity modulation. In vitro studies indicate that vortioxetine is an inhibitor
      of the 5-HT transporter and is a 5-HT(1D), 5-HT3 and 5-HT7 receptor antagonist, a
      5-HT(1A) receptor agonist and a 5-HT(1B) receptor partial agonist. Animal and in
      vitro studies indicate that several neurotransmitter systems may be impacted by
      vortioxetine, with the drug enhancing levels of 5-HT, noradrenaline, dopamine,
      acetylcholine and histamine in certain areas of the brain, as well as modulating
      gamma-aminobutyric acid and glutamate neurotransmission. Phase III trials of
      vortioxetine in both MDD and GAD have been conducted worldwide. This article
      summarizes the milestones in the development of vortioxetine leading to this
      first approval for MDD.

PMID- 24311351
TI  - A transpersonal critique of behaviorism.
AB  - Behavioral psychology has been neglected by pastoral psychologists to the hurt of
      both. An examination of the principles of behaviorism and some of the data on the
      behavioral treatment of the neuroses is followed by an analysis of B.F. Skinner's
      philosophy of science. A critique is developed from the perspective of
      transpersonal psychology, concluding with a possible reconciliation of the
      opposites of behavioral and transpersonal ways of knowing. 

PMID- 24311352
TI  - Dependence and manhood.
AB  - American culture is at best ambivalent and at worst hostile to the
      appropriateness of dependency in males. To reorient this cultural misconception,
      a healthful model of male dependency is needed-especially for health care and
      pastoral professionals. This paper offers such a construct by bringing the
      perspectives of a theologian, Dietrich Bonhoeffer, and a psychoanalyst, Heinz
      Kohut, to an examination of this issue. Out of this discussion, an ethic can be
      formulated which offers guidelines for the exercise of male dependency and a more
      complete model of manhood. 

PMID- 24311353
TI  - The self ideal versus the model ideal.
AB  - A list of 50 ways of perceiving one's personal ideal was constructed and
      administered to 74 women about to make a lifelong commitment. The mean number of
      items endorsed was 28. An item analysis yielded discrimination indices for 28
      items at better than the .05 level of significance. These attitudes were
      discussed as less motivativing, and opposite attitudes from the same point of
      view were grouped under six principles of motivation: dominant relationship,
      closeness, growth, valuational center, similarity, realism. From these two
      diametrically opposite perceptual structures of attitudes emerged the self ideal
      and the model ideal. 

PMID- 24311354
TI  - In defense of monotheistic father religion.
AB  - Many questions are currently being raised, by women especially, regarding the
      religious, social, and psychological effects of the emphasis on God as father in
      Western religion. Viewed in the light of key insights from developmental
      psychoanalysis, patriarchal monotheism does indeed seem to confront us with a
      dilemma. However, a resolution of this dilemma does not appear to lie in a move
      toward androgyny or matriarchy. Evaluated from the point of view of its overall
      capacity to mediate a meaningful, unified, personal religious reality to both
      sexes, monotheistic father religion is still the preferable ultimate symbolic
      configuration. 

PMID- 24311355
TI  - Religious faith and adjustment to long-term hemodialysis.
AB  - This study examines religious faith as associated with adjustment to end-stage
      renal failure and its treatment regimen of maintenance hemodialysis. Both
      quantitative and qualitative data were collected initially and after a three-year
      interval in order to observe changes over time. The variable of the patient's
      perception of the import of religious faith was found to be positively related to
      interactional behavior and sick role behavior and to be inversely associated with
      alienation. Content analysis of qualitative responses for the item of perceived
      import of religious faith revealed a pattern of increasingly more positive
      patient attitudes occurring over time. 

PMID- 24311356
TI  - The polar unities as a guide to psychotherapy.
AB  - The author recognizes the need for a psychotherapy that aims to be either
      spiritual or wholistic to ground itself in appropriate philosophical and
      theological constructs. As one small step in this direction, the ontological
      elements as discussed by Paul Tillich are applied to some specific therapeutic
      issues. Striking parallels are found between Tillich's first two ontological
      elements (individualization-participation, and dynamics-form) and the two
      dimensions (cohesion and adaptability) of the circumplex model of family therapy.
      It is suggested that Tillich's third ontological element (freedom-destiny) throws
      useful light on the educational and psychotherapeutic issue of permissiveness
      versus authoritarianism. 

PMID- 24311357
TI  - Role of neuronal nicotinic acetylcholine receptors (nAChRs) on learning and
      memory in zebrafish.
AB  - RATIONALE: Neuronal nicotinic acetylcholine receptors (nAChRs) play a modulatory
      role in cognition, and zebrafish provide a preclinical model to study learning
      and memory. OBJECTIVES: We investigated the effect of nicotine (NIC) and some new
      cytisine-derived partial agonists (CC4 and CC26) on spatial memory in zebrafish
      using a rapid assay on T-maze task. The role of alpha4/alpha6beta2 and the alpha7
      nAChRs in NIC-induced memory enhancement was evaluated using selective nAChR
      antagonists. RESULTS: Low and high doses of NIC, cytisine (CYT), CC4 and CC26
      respectively improved and worsened the mean running time, showing an inverted U
      dose-response function. The effective dose (ED50) (*10-5 mg/kg) was 0.4 for CC4,
      4.5 for CYT, 140 for NIC and 200 for CC26. NIC-induced cognitive enhancement was
      reduced by the selective nAChR subtype antagonists: methyllycaconitine (MLA) for
      alpha7, alpha-conotoxin (MII) for alpha6beta2, dihydro-beta-erythroidine
      (DhbetaE) for alpha4beta2, the nonselective antagonist mecamylamine (MEC) and the
      muscarinic antagonist scopolamine (SCOP), with DhbetaE being more active than MLA
      or MII. All the partial agonists blocked the cognitive enhancement. The
      improvement with the maximal active dose of each partial agonist was blocked by
      low doses of DhbetaE (0.001 mg/kg) and MII (0.01 mg/kg). MLA reduced the effects
      of CC26 and CC4 at doses of 0.01 and 1 mg/kg, respectively, but did not
      antagonize CYT-induced memory improvement at any of the tested dose. No change in
      swimming activity was observed. CONCLUSIONS: Our findings demonstrate that
      zebrafish make a useful model for the rapid screening of the effect of new
      alpha4beta2 nAChR compounds on spatial memory.

PMID- 24311358
TI  - Disrupted social development enhances the motivation for cocaine in rats.
AB  - RATIONALE: Early social experiences are of major importance for behavioural
      development. In particular, social play behaviour during post-weaning development
      is thought to facilitate the attainment of social, emotional and cognitive
      capacities. Conversely, social insults during development can cause long-lasting
      behavioural impairments and increase the vulnerability for psychiatric disorders,
      such as drug addiction. OBJECTIVES: The aim of this study was to investigate
      whether a lack of social experiences during the juvenile and early adolescent
      stage, when social play behaviour is highly abundant, alters cocaine self
      administration in rats. METHODS: Rats were socially isolated from postnatal days
      21 to 42 followed by re-socialization until adulthood. Cocaine self
      administration was then assessed under a fixed ratio and progressive ratio
      schedule of reinforcement. Next, cue, cocaine and stress-induced reinstatement of
      cocaine seeking was determined following extinction of self-administration.
      RESULTS: Early social isolation resulted in an enhanced acquisition of self
      administration of a low dose (0.083 mg/infusion) of cocaine, but the sensitivity
      to cocaine reinforcement, assessed using a dose-response analysis, was not
      altered in isolated rats. Moreover, isolated rats displayed an increased
      motivation for cocaine under a progressive ratio schedule of reinforcement.
      Extinction and reinstatement of cocaine seeking was not affected by early social
      isolation. CONCLUSIONS: Early social isolation causes a long-lasting increase in
      the motivation to self-administer cocaine. Thus, aberrations in post-weaning
      social development, such as the absence of social play, enhance the vulnerability
      for drug addiction later in life.

PMID- 24311359
TI  - Prenatal corticosterone and adolescent URB597 administration modulate
      emotionality and CB1 receptor expression in mice.
AB  - RATIONALE: The central endocannabinoid system (eCB system) sustains the activity
      of the hypothalamus-pituitary-adrenal (HPA) axis in mediating individual
      emotional responses. Deviation in maturational trajectories of these two
      physiological systems, may persistently adjust individual behavioral phenotype.
      OBJECTIVE: We investigated, in outbred CD1 male mice, whether exposure to
      prenatal stress may influence short- and long-term emotional and neurochemical
      responses to a pharmacological stimulation of the eCB system during adolescence.
      METHODS: To mimic prenatal stress, pregnant mice were supplemented with
      corticosterone in the drinking water (33.3 mg/l); their adolescent male offspring
      received daily injections of the fatty acid amide hydrolase inhibitor, URB597
      (0.4 mg/kg), in order to enhance eCB signaling. Mice were then tested for:
      locomotor activity during adolescence and locomotor activity, anxiogenic, and
      anhedonic profiles in adulthood. We analyzed the expression of CB1 receptors
      (CB1Rs) in prefrontal cortex, hippocampus, striatum, and cerebellum in adulthood.
      RESULTS: Corticosterone administration (PC group) resulted, in adolescence, in a
      reduction in body weight and locomotion, while in adulthood, in increased anxiety
      related behavior and reduced CB1Rs expression in cerebellum. URB597 exposure
      reduced locomotor activity and increased anhedonia in adulthood. CB1Rs were up
      regulated in striatum and hippocampus and down-regulated in the cerebellum. PC
      URB597 mice failed to show reductions in locomotion; exhibited increased risk
      assessment behavior; and showed reduced CB1Rs expression within the prefrontal
      cortex. CONCLUSIONS: Present results provide support to the hypothesis that
      precocious manipulations mapping onto the HPA axis and eCB system may
      persistently adjust individual emotional responses and eCB system plasticity.

PMID- 24311361
TI  - Medial defects of the small pulmonary arteries in fatal pulmonary hypertension in
      infants with trisomy 13 and trisomy 18.
AB  - Congestive heart failure is a major cause of early death in patients with trisomy
      13 or 18 and congenital heart disease (CHD). Pulmonary artery banding for these
      patients early in life is preferred to protect the lungs from high pulmonary flow
      rates and improve survival. We performed open lung biopsies in 11 patients with
      trisomy 13 or 18 accompanied by CHD and severe pulmonary artery hypertension
      (PAH) between 2009 and 2011. Two (18.2%) of these 11 patients had medial defects
      of the small pulmonary arteries. One patient with trisomy 13 and an atrial septal
      defect developed lung hemorrhage and lung edema at the age of 9 months and died
      at the age of 13 months. The lumens of the small pulmonary arteries of the other
      patient with trisomy 18 and a ventricular septal defect became occluded due to
      the intimal proliferation of fibrous tissues at the age of 2 months. This patient
      died at the age of 27 months. The deaths of both patients were associated with
      heart-related factors. Patients with medial defects are vulnerable to intimal
      proliferation in the small pulmonary arteries. More patients with trisomy 13 or
      18 and CHD might have similar pulmonary vascular changes. The small pulmonary
      arteries of patients with trisomy 13 and 18 should be further analyzed.

PMID- 24311360
TI  - Spiritual struggle and affective symptoms among geriatric mood disordered
      patients.
AB  - OBJECTIVES: We explored relationships between general religiousness, positive
      religious coping, negative religious coping (spiritual struggle), and affective
      symptoms among geriatric mood disordered outpatients, in the northeastern USA.
      METHODS: We assessed for general religiousness (religious affiliation, belief in
      God, and private and public religious activity) and positive/negative religious
      coping, alongside interview and self-report measures of affective functioning in
      a diagnostically heterogeneous sample of n = 34 geriatric mood disordered
      outpatients (n = 16 bipolar and n = 18 major depressive) at a psychiatric
      hospital in eastern Massachusetts. RESULTS: Except for a modest correlation
      between private prayer and lower Geriatric Depression Scale scores, general
      religious factors (belief in God, public religious activity, and religious
      affiliation) as well as positive religious coping were unrelated to affective
      symptoms after correcting for multiple comparisons and controlling for
      significant covariates. However, a large effect of spiritual struggle was
      observed on greater symptom levels (up to 19.4% shared variance). Further, mean
      levels of spiritual struggle and its observed effects on symptoms were equivalent
      irrespective of religious affiliation, belief, and private and public religious
      activity. CONCLUSIONS: Previously observed effects of general religiousness on
      (less) depression among geriatric mood disordered patients may be less pronounced
      in less religious areas of the USA. However, spiritual struggle appears to be a
      common and important risk factor for depressive symptoms, regardless of patients'
      general level of religiousness. Further research on spiritual struggle is
      warranted among geriatric mood disordered patients.

PMID- 24311362
TI  - Perinatal maternal stress and serotonin signaling: effects on pain sensitivity in
      offspring.
AB  - It has been estimated that 20% of pregnant women are facing perinatal stress and
      depression. Perinatal maternal stress has been shown to increase pain sensitivity
      in offspring. For the treatment of their depressive symptoms, pregnant women are
      frequently prescribed selective serotonin reuptake inhibitors (SSRIs). Since the
      descending pain inhibitory circuit matures perinatally, perinatal SSRI exposure
      has been shown to affect pain sensitivity in offspring. In the present review, we
      summarize experimental and clinical evidence for the effect of perinatal maternal
      stress and SSRI exposure on pain sensitivity in offspring. Both experimental and
      clinical studies show the effect of perinatal maternal stress on regulation of
      the hypothalamic-pituitary-adrenal (HPA) system and the serotonin pain inhibitory
      system. Alterations in these two systems likely underlie long-term alterations in
      the development of pain sensitivity. This review sheds light on the effect of
      perinatal maternal stress and treatment with SSRIs on offspring pain sensitivity,
      in relation to the developing HPA system and 5-HT signaling.

PMID- 24311364
TI  - Mild developmental delay and obesity in two patients with mosaic 1p36 deletion
      syndrome.
AB  - We identified mosaic 1p36 deletions in two patients with developmental delay,
      distinctive features, and obesity, who can walk alone and communicate with
      others. Thus, their neurological defects are milder than those in typical
      patients with 1p36 deletion syndrome because most patients with 1p36 deletion
      cannot acquire expressive language. Chromosomal microarray testing revealed 3.0
      and 4.5 Mb aberrations in the subtelomeric region of the short arm of chromosome
      1. Mean signal ratios of the identified aberrations were -0.4 and -0.5,
      indicating mosaicism, which was confirmed by fluorescence in situ hybridization
      analysis with a mosaic ratio of 70% and 77%, respectively. Previous studies
      demonstrated that deletion of the distal 2-3 Mb region would be responsible for
      hyperphagia and obesity seen in patients. On the other hand, the severity of the
      neurological defect often correlates with the size of the terminal deletion of
      1p36, and patients with larger deletions of 1p36 would usually show severely
      impaired developmental milestones and be immobile and aphasic. In such cases,
      hyperphagia and obesity could be clinically masked. In this study, two patients
      with mosaic deletions of 1p36 showed obesity as a consequence of hyperphagia.
      This study suggests that patients with 1p36 deletion would be at risk for
      hyperphagia and obesity when they have both risk factors, that is, (1) deletions
      including the 2-3 Mb critical region and (2) milder phenotypes that allow them to
      reach food on their own and to overeat.

PMID- 24311363
TI  - Functional interpretation of non-coding sequence variation: concepts and
      challenges.
AB  - Understanding the functional mechanisms underlying genetic signals associated
      with complex traits and common diseases, such as cancer, diabetes and Alzheimer's
      disease, is a formidable challenge. Many genetic signals discovered through
      genome-wide association studies map to non-protein coding sequences, where their
      molecular consequences are difficult to evaluate. This article summarizes
      concepts for the systematic interpretation of non-coding genetic signals using
      genome annotation data sets in different cellular systems. We outline strategies
      for the global analysis of multiple association intervals and the in-depth
      molecular investigation of individual intervals. We highlight experimental
      techniques to validate candidate (potential causal) regulatory variants, with a
      focus on novel genome-editing techniques including CRISPR/Cas9. These approaches
      are also applicable to low-frequency and rare variants, which have become
      increasingly important in genomic studies of complex traits and diseases. There
      is a pressing need to translate genetic signals into biological mechanisms,
      leading to prognostic, diagnostic and therapeutic advances. 

PMID- 24311365
TI  - A simplified approach for the rehabilitation of an auricular defect: a case
      report.
AB  - BACKGROUND AND AIM: Replacement of missing ear is a challenging task in which
      extensive array of materials and techniques have been employed. Materials such as
      silicones and methacrylate acrylic resins have been widely used for auricular
      prosthesis. This article describes a simplified procedure for fabricating
      resilient heat-cured acrylic resin auricular prosthesis, retained with a custom
      made acrylic bar with ball attachments. CASE DESCRIPTION AND METHODS: A male
      patient was reported with right ear loss. A modified technique was preferred to
      fabricate ear prosthesis with resilient heat-cured acrylic resin in which heat
      cured acrylic retentive bar was incorporated. FINDINGS AND OUTCOMES: Contrary to
      silicones, resilient heat-cured acrylic resin was more economical and compatible
      with acrylic retentive bar and resulted in a more long-lasting auricular
      prosthesis. CONCLUSION: Resilient heat-cured acrylic resin was proven to be a
      better alternative in terms of strength and durability. CLINICAL RELEVANCE: This
      article presents an economical and simplified approach for the fabrication of
      prosthesis for a missing ear.

PMID- 24311366
TI  - Development of an extended-release formulation of capecitabine making use of in
      vitro-in vivo correlation modelling.
AB  - An oral extended-release (ER) formulation of capecitabine was developed for twice
      daily dosing, theoretically providing a continuous exposure to capecitabine, thus
      avoiding the undesirable in-between dosing gap inherent to the dosing schedule of
      the marketed capecitabine immediate-release formulation (Xeloda((r))). The target
      12-hour in vivo release profile was correlated to an in vitro dissolution profile
      using an in vitro-in vivo correlation model based on the pharmacokinetic (PK) and
      dissolution characteristics of Xeloda((r)). Making use of the slow dissolution
      characteristics of amorphous capecitabine as reported previously and screening of
      a panel of ER excipients, an ER formulation was designed. Kollidon((r)) SR
      induced the most prominent ER. Moreover, it was shown that tablets prepared from
      CoSD capecitabine and Kollidon((r)) SR have an additional threefold delay in
      dissolution compared with tablets prepared from the same but only physically
      mixed components. Therefore, a prototype tablet formulation composed of co-spray
      dried capecitabine and Kollidon((r)) SR (98/2%, w/w) mixed with colloidal silicon
      dioxide (0.5%, w/w) and magnesium stearate (2.5%, w/w) was defined. This
      prototype shows similar dissolution characteristics as the modelled dissolution
      profile. Currently, the in vivo PK of our designed ER capecitabine formulations
      is investigated in a clinical study.

PMID- 24311367
TI  - Involving patients in research: considering good practice.

PMID- 24311368
TI  - Tetrafluorination of sugars as strategy for enhancing protein-carbohydrate
      affinity: application to UDP-Galp mutase inhibition.
AB  - Tetrafluorinated analogues of both UDP-galactopyranose and UDP-galactofuranose
      have been synthesized and assayed against UDP-galactopyranose mutase, a key
      enzyme for Mycobacterium tuberculosis cell wall biosynthesis. Competition assays
      and STD-NMR spectroscopy techniques have evidenced not only the first unambiguous
      case of affinity enhancement through local sugar polyfluorination, but also
      showed that tetrafluorination can still have a beneficial effect on binding when
      monofluorination at the same position does not.

PMID- 24311369
TI  - Lactose as a "Trojan horse" for quantum dot cell transport.
AB  - A series of glycan-coated quantum dots were prepared to probe the effect of
      glycan presentation in intracellular localization in HeLa and SV40 epithelial
      cells. We show that glycan density mostly impacts on cell toxicity, whereas
      glycan type affects the cell uptake and intracellular localization. Moreover, we
      show that lactose can act as a "Trojan horse" on bi-functionalized QDs to help
      intracellular delivery of other non-internalizable glycan moieties and largely
      avoid the endosomal/lysosomal degradative pathway. 

PMID- 24311370
TI  - Pituitary deficiency and congenital infiltrating lipomatosis of the face in a
      girl with deletion of chromosome 1q24.3q31.1.
AB  - Interstitial deletions of the long arm of chromosome 1 are rare and they are
      classified as proximal or intermediate. The intermediate interstitial deletions
      span 1q24-1q32. We describe a 6-year-old girl with multiple pituitary hormone
      deficiency, severe cognitive impairment, bilateral cleft lip and palate, midline
      facial capillary malformation, erythema of hands and feet and dysplastic cranial
      vessels, low anti-thrombin III activity, hemifacial overgrowth due to progressive
      infiltrating lipomatosis with bone overgrowth, marked vascular proliferation and
      erythema of hands and feet, and abnormal cranial vessels. The girl's karyotype
      showed an apparently de novo interstitial deletion 1q24.3q31.1, which was defined
      by array-CGH. The deleted region contains numerous genes, but only eight (CENPL,
      LHX4, LAMC1, LAMC2, PTGS2, ANGPTL1, TNN, and TNR) are good candidates to explain,
      at least partially, the phenotype of the proposita. We, therefore, discuss the
      involvement of these genes and the observed phenotype.

PMID- 24311371
TI  - Ageing and trajectories of depressive symptoms in community-dwelling men and
      women.
AB  - OBJECTIVE: The aim of this study was to investigate age-related patterns of
      depressive symptoms in older men and women and to identify their determinants.
      METHODS: The Center for Epidemiological Studies Depression Scale was used to
      prospectively assess depressive symptoms in 1059 men and 1531 women, enrolled in
      a French representative population-based cohort (PAQUID study) and followed over
      a period of 20 years. Using a group-based trajectory method with an accelerated
      longitudinal design, we modelled the course of depressive symptoms between 65 and
      104 years of age and examined associations between trajectory patterns and
      baseline socio-demographic and health variables. RESULTS: In men, we identified
      three rising trajectories: 'never depressed' including 65% of the sample,
      'emerging depression' (28%) and 'increasing depression' (7%). Compared with the
      membership of the never-depressed trajectory, that of the two higher trajectories
      was significantly associated with a history of depression and dyspnoea. In women,
      we identified two slightly rising trajectories (never depressed, 56%, and 'rising
      subclinical', 33%) and one stable high trajectory ('persistent depression', 11%).
      Membership of the two higher trajectories was significantly associated with the
      use of benzodiazepine, polymedication and dyspnoea. A history of nondepressive
      psychiatric disorder was a risk factor for membership of the persistent
      depression group, whereas being widowed seemed to be a protective factor for
      membership of this group. CONCLUSION: High-risk groups for later-life depression
      should be targeted differently in older men and women in order to implement
      appropriate interventions to prevent chronicity and disability.

PMID- 24311372
TI  - Simultaneous determination of corosolic acid and euscaphic acid in the plasma of
      normal and diabetic rat after oral administration of extract of Potentilla
      discolor Bunge by high-performance liquid chromatography/electrospray ionization
      mass spectrometry.
AB  - Potentilla discolor Bunge has been used for diabetes in China for a long time.
      Corosolic acid (CA) and euscaphic acid (EA), with significant anti-diabetic
      activity, are two major triterpenoids in P. discolor. In this study, a specific,
      sensitive and convenient LC-MS method has been developed for simultaneous
      determination of CA and EA in the plasma of normal and diabetic rats after oral
      administration of the extract of P. discolor. The chromatographic separation was
      achieved using an Alltima C18 column (53 * 7.0 mm, i.d., 3 um) with a mobile
      phase composed of 0.1% formic acid water and 0.1% formic acid acetonitrile at a
      flow rate of 1.0 mL/min. The detection was performed by MS with electrospray
      ionization interface in negative selected ion monitoring mode. All the validation
      data, such as specificity, linearity (r(2)  > 0.9991 within 0.025-10.0 ug/mL),
      lower limit of quantitation (2.5 ng/mL), precision (intra- and inter-day <14.7%),
      accuracy (<15.0%), recovery (85.7-110.8%) and stability were determined and all
      of them were within the required limits. This method was successfully applied for
      the evaluation of the pharmacokinetic behaviors of these two compounds in the
      plasma of normal and diabetic rats.

PMID- 24311373
TI  - Dropwise additive manufacturing of pharmaceutical products for solvent-based
      dosage forms.
AB  - In recent years, the US Food and Drug Administration has encouraged
      pharmaceutical companies to develop more innovative and efficient manufacturing
      methods with improved online monitoring and control. Mini-manufacturing of
      medicine is one such method enabling the creation of individualized product forms
      for each patient. This work presents dropwise additive manufacturing of
      pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing
      method that deposits active pharmaceutical ingredients (APIs) directly onto
      edible substrates using drop-on-demand (DoD) inkjet printing technology. The use
      of DoD technology allows for precise control over the material properties, drug
      solid state form, drop size, and drop dynamics and can be beneficial in the
      creation of high-potency drug forms, combination drugs with multiple APIs or
      individualized medicine products tailored to a specific patient. In this work,
      DAMPP was used to create dosage forms from solvent-based formulations consisting
      of API, polymer, and solvent carrier. The forms were then analyzed to determine
      the reproducibility of creating an on-target dosage form, the morphology of the
      API of the final form and the dissolution behavior of the drug over time. DAMPP
      is found to be a viable alternative to traditional mass-manufacturing methods for
      solvent-based oral dosage forms.

PMID- 24311374
TI  - Combined immunodeficiency in a 3-year-old boy with 16p11.2 and 20p12.2-11.2
      chromosomal duplications.
AB  - We report for the first time on a 3-year-old boy with paternally inherited 212.85
      kb-16p11.2 and 7.8 Mb-20p12.2-11.23 interstitial microduplications associated
      with having congenital cardiac defect, dysmorphic facial features, and combined T
      , B-, and NK cell immunodeficiency. In addition the 7.8 Mb-20p12.2-11.23
      microduplication is unique showing novel breakpoints among all partial
      trisomy/duplication 20p reported to date, narrowing down the critical region for
      trisomy 20p syndrome.

PMID- 24311375
TI  - IL-17, an important prognostic factor and potential therapeutic target for breast
      cancer?

PMID- 24311376
TI  - Erythrocyte-derived microvesicles amplify systemic inflammation by thrombin
      dependent activation of complement.
AB  - OBJECTIVE: Transfusion of aged blood has been associated with increased morbidity
      and mortality in critically ill patients. During storage, erythrocytes release
      increasing numbers of microvesicles (red blood cell-derived microvesicles [RBC
      MV]). We hypothesized that RBC-MV mediate some of the deleterious effects of aged
      blood transfusions. APPROACH AND RESULTS: We established a murine transfusion
      model using RBC-MV purified from aged mouse erythrocytes. Injection of RBC-MV
      into healthy mice had no effect. However, they aggravated pulmonary leukocyte
      sequestration and peripheral blood leukopenia induced by lipopolysaccharides.
      Lipopolysaccharide-induced proinflammatory cytokines were significantly increased
      in plasma after RBC-MV injection. These effects were not seen in C5aR-deficient
      mice. In vitro, RBC-MV bound C3 fragments after incubation with plasma but failed
      to bind immunoglobulins, C1q, or mannose-binding lectin. Preventing thrombin
      generation inhibited complement activation in vitro and in vivo and reversed the
      proinflammatory effects of RBC-MV in lipopolysaccharide-primed mice. Finally, the
      RBC-MV-induced phenotype was recapitulated using phosphatidylserine-expressing
      liposomes, suggesting that surface expression of phosphatidylserine by RBC-MV was
      mechanistically involved. CONCLUSIONS: These results point toward a thrombin
      dependent mechanism of complement activation by RBC-MV independent of the
      classical, lectin, or alternative pathway. Besides identifying RBC-MV as
      potential mediators of transfusion-related morbidity, our findings may be
      relevant for other inflammatory disorders involving intravascular microvesicle
      release, for example, sickle cell disease or thrombotic microangiopathy.

PMID- 24311377
TI  - Genetic reduction of vascular endothelial growth factor receptor 2 rescues
      aberrant angiogenesis caused by epsin deficiency.
AB  - OBJECTIVE: We previously showed that endothelial epsin deficiency caused elevated
      vascular endothelial growth factor receptor 2 (VEGFR2) and enhanced VEGF
      signaling, resulting in aberrant tumor angiogenesis and reduced tumor growth in
      adult mice. However, direct evidence demonstrating that endothelial epsins
      regulate angiogenesis specifically through VEGFR2 downregulation is still
      lacking. In addition, whether the lack of epsins causes abnormal angiogenesis
      during embryonic development remains unclear. APPROACH AND RESULTS: A novel
      strain of endothelial epsin-deleted mice that are heterozygous for VEGFR2
      (Epn1(fl/fl); Epn2(-/-); Flk(fl/+); iCDH5 Cre mice) was created. Analysis of
      embryos at different developmental stages showed that deletion of epsins caused
      defective embryonic angiogenesis and retarded embryo development. In vitro
      angiogenesis assays using isolated primary endothelial cells (ECs) from
      Epn1(fl/fl); Epn2(-/-); iCDH5 Cre (EC-iDKO) and Epn1(fl/fl); Epn2(-/-);
      Flk(fl/+); iCDH5 Cre (EC-iDKO-Flk(fl/+)) mice demonstrated that VEGFR2 reduction
      in epsin-depleted cells was sufficient to restore normal VEGF signaling, EC
      proliferation, EC migration, and EC network formation. These findings were
      complemented by in vivo wound healing, inflammatory angiogenesis, and tumor
      angiogenesis assays in which reduction of VEGFR2 was sufficient to rescue
      abnormal angiogenesis in endothelial epsin-deleted mice. CONCLUSIONS: Our results
      provide the first genetic demonstration that epsins function specifically to
      downregulate VEGFR2 by mediating activated VEGFR2 internalization and degradation
      and that genetic reduction of VEGFR2 level protects against excessive
      angiogenesis caused by epsin loss. Our findings indicate that epsins may be a
      potential therapeutic target in conditions in which tightly regulated
      angiogenesis is crucial, such as in diabetic wound healing and tumors.

PMID- 24311378
TI  - A novel mouse model of aortic valve stenosis induced by direct wire injury.
AB  - OBJECTIVE: The response-to-tissue-injury theory is currently the favorite
      paradigm to investigate valve pathology. To the best of our knowledge, there are
      currently no in vivo valve injury models. There are few calcific aortic valve
      stenosis (AVS) models that develop hemodynamically significant stenosis. Here, we
      investigated the effect of direct mechanical injury on aortic valves in vivo and
      developed a novel mouse model of calcific AVS. APPROACH AND RESULTS: Aortic valve
      injury was created by inserting and moving a spring guidewire under
      echocardiographic guidance into the left ventricle of male C57/BL6 mice via right
      common carotid artery. Serial echocardiographic measurements revealed that aortic
      velocity was increased 1 week after injury and persistently increased until 16
      weeks after injury. AVS mice showed a higher heart weight/body weight ratio and
      decreased left ventricular fractioning shortening 4 weeks after injury, compared
      with sham mice. We found remarkable proliferation of valve leaflets 4 weeks after
      injury. Proliferative valves showed increased production of reactive oxygen
      species and expression of inflammatory cytokines and osteochondrogenic factors.
      Alizarin red staining showed valvular calcification 12 weeks after injury.
      CONCLUSIONS: We report a novel calcific AVS model to support the response-to
      tissue-injury theory. This model may be a valuable tool for analyzing the
      mechanism of AVS and assessing therapeutic options.

PMID- 24311379
TI  - Essential role of Apelin signaling during lymphatic development in zebrafish.
AB  - OBJECTIVE: Apelin and its cognate receptor Aplnr/Apj are essential for diverse
      biological processes. However, the function of Apelin signaling in lymphatic
      development remains to be identified, despite the preferential expression of
      Apelin and Aplnr within developing blood and lymphatic endothelial cells in
      vertebrates. In this report, we aim to delineate the functions of Apelin
      signaling during lymphatic development. APPROACH AND RESULTS: We investigated the
      functions of Apelin signaling during lymphatic development using zebrafish
      embryos and found that attenuation of Apelin signaling substantially decreased
      the formation of the parachordal vessel and the number of lymphatic endothelial
      cells within the developing thoracic duct, indicating an essential role of Apelin
      signaling during the early phase of lymphatic development. Mechanistically, we
      found that abrogation of Apelin signaling selectively attenuates lymphatic
      endothelial serine-threonine kinase Akt 1/2 phosphorylation without affecting the
      phosphorylation status of extracellular signal-regulated kinase 1/2. Moreover,
      lymphatic abnormalities caused by the reduction of Apelin signaling were
      significantly exacerbated by the concomitant partial inhibition of serine
      threonine kinase Akt/protein kinase B signaling. Apelin and vascular endothelial
      growth factor-C (VEGF-C) signaling provide a nonredundant activation of serine
      threonine kinase Akt/protein kinase B during lymphatic development because
      overexpression of VEGF-C or apelin was unable to rescue the lymphatic defects
      caused by the lack of Apelin or VEGF-C, respectively. CONCLUSIONS: Taken
      together, our data present compelling evidence suggesting that Apelin signaling
      regulates lymphatic development by promoting serine-threonine kinase Akt/protein
      kinase B activity in a VEGF-C/VEGF receptor 3-independent manner during zebrafish
      embryogenesis.

PMID- 24311380
TI  - Aldosterone promotes vascular remodeling by direct effects on smooth muscle cell
      mineralocorticoid receptors.
AB  - OBJECTIVE: Vascular remodeling occurs after endothelial injury, resulting in
      smooth muscle cell (SMC) proliferation and vascular fibrosis. We previously
      demonstrated that the blood pressure-regulating hormone aldosterone enhances
      vascular remodeling in mice at sites of endothelial injury in a placental growth
      factor-dependent manner. We now test the hypothesis that SMC mineralocorticoid
      receptors (MRs) directly mediate the remodeling effects of aldosterone and
      further explore the mechanism. APPROACH AND RESULTS: A wire-induced carotid
      injury model was performed in wild-type mice and mice with inducible SMC-specific
      deletion of the MR. Aldosterone did not affect re-endothelialization after injury
      in wild-type mice. Deletion of SMC-MR prevented the 79% increase in SMC
      proliferation induced by aldosterone after injury in MR-Intact littermates.
      Moreover, both injury-induced and aldosterone-enhanced vascular fibrosis were
      attenuated in SMC-specific MR knockout mice. Further exploration of the mechanism
      revealed that aldosterone-induced vascular remodeling is prevented by in vivo
      blockade of the placental growth factor-specific receptor, type 1 vascular
      endothelial growth factor receptor (VEGFR1), the receptor for placental growth
      factor. Immunohistochemistry of carotid vessels shows that the induction of
      VEGFR1 expression in SMC after vascular injury is attenuated by 72% in SMC
      specific MR knockout mice. Moreover, aldosterone induction of vascular placental
      growth factor mRNA expression and protein release are also prevented in vessels
      lacking SMC-MR. CONCLUSIONS: These studies reveal that SMC-MR is necessary for
      aldosterone-induced vascular remodeling independent of renal effects on blood
      pressure. SMC-MR contributes to induction of SMC VEGFR1 in the area of vascular
      injury and to aldosterone-enhanced vascular placental growth factor expression
      and hence the detrimental effects of aldosterone are prevented by VEGFR1
      blockade. This study supports exploring MR antagonists and VEGFR1 blockade to
      prevent pathological vascular remodeling induced by aldosterone.

PMID- 24311381
TI  - Activation of liver X receptor decreases atherosclerosis in Ldlr-/- mice in the
      absence of ATP-binding cassette transporters A1 and G1 in myeloid cells.
AB  - OBJECTIVE: Liver X receptor (LXR) activators decrease atherosclerosis in mice.
      LXR activators (1) directly upregulate genes involved in reverse cholesterol
      transport and (2) exert anti-inflammatory effects mediated by transrepression of
      nuclear factor-kappaB target genes. We investigated whether myeloid cell
      deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal
      targets of LXR that promote macrophage cholesterol efflux and initiate reverse
      cholesterol transport, would abolish the beneficial effects of LXR activation on
      atherosclerosis. APPROACH AND RESULTS: LXR activator T0901317 substantially
      reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr(-/-)
      mice were transplanted with Abca1(-/-)Abcg1(-/-) or wild-type bone marrow (BM)
      and fed a Western-type diet for 6 weeks with or without T0901317 supplementation.
      Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and
      inflammatory cell infiltration into the adventitia and myocardium. T0901317
      markedly decreased lesion area, complexity, and inflammatory cell infiltration in
      the Abca1(-/-)Abcg1(-/-) BM-transplanted mice. To investigate whether this was
      because of macrophage Abca1/g1 deficiency, Ldlr(-/-) mice were transplanted with
      LysmCreAbca1(fl/fl)Abcg1(fl/fl) or Abca1(fl/fl)Abcg1(fl/fl) BM and fed Western
      type diet with or without the more specific LXR agonist GW3965 for 12 weeks.
      GW3965 decreased lesion size in both groups, and the decrease was more prominent
      in the LysmCreAbca1(fl/fl)Abcg1(fl/fl) group. CONCLUSIONS: The results suggest
      that anti-inflammatory effects of LXR activators are of key importance to their
      antiatherosclerotic effects in vivo independent of cholesterol efflux pathways
      mediated by macrophage ABCA1/G1. This has implications for the development of LXR
      activators that lack adverse effects on lipogenic genes while maintaining the
      ability to transrepress inflammatory genes.

PMID- 24311383
TI  - Heathcock-inspired strategies for the synthesis of fawcettimine-type Lycopodium
      alkaloids.
AB  - The fawcettimine-type Lycopodium alkaloids have garnered significant attention
      from synthetic organic chemists since the isolation of fawcettimine in 1959.
      Despite being targets of interest for over 50 years, most of the strategies
      employed in the syntheses of fawcettimine congeners have built upon Inubushi and
      Heathcock's original work, realized in 1979 and 1986, respectively. This elegant
      strategy has been explored and expanded upon in the intervening years since the
      original publications, in what we now call the Heathcock-inspired strategy. While
      other disconnections have been disclosed, this strategy remains one of the most
      efficient. In this Concept article, we focus on exploring a number of recent
      Heathcock-inspired syntheses of fawcettimine-type Lycopodium alkaloids. We also
      briefly discuss alternative, novel disconnections.

PMID- 24311382
TI  - Deletion of cysteine-cysteine receptor 7 promotes fibrotic injury in experimental
      post-thrombotic vein wall remodeling.
AB  - OBJECTIVE: Deep vein thrombosis (VT) can result in vein wall injury, which
      clinically manifests as post-thrombotic syndrome. Postinjury fibrosis may be
      modulated in part through cellular cysteine-cysteine receptor 7 (CCR7)-mediated
      events. We tested the hypothesis that late vein wall fibrotic remodeling is
      dependent on CCR7. APPROACH AND RESULTS: CCR7(-/-) and C57BL/6 wild-type mice had
      inferior vena cava VT induced by nonstasis or stasis mechanisms. In both models,
      VT size was largest at day 1 and trended down by day 21, and CCR7(+) cells peaked
      at day 8 in wild-type mice. No significant differences in VT resolution were
      found in CCR7(-/-) as compared with wild type in either model. In the nonstasis
      VT model, vein wall changes consistent with fibrotic injury were evidenced by
      significant increases in collagen I, III, matrix metalloproteinase 2, and
      transforming growth factor-beta gene expression, increases in alpha-smooth muscle
      actin and fibroblast specific protein-1 antigen, and total collagen at 8 days.
      Correspondingly, SM22alpha and fibroblast specific protein-1, but not DDR2(+)
      cells, were increased at 8 days. Early wild-type thrombus exposure inhibited
      profibrotic gene expression in CCR7(-/-) in ex vivo vein wall culture. Bone
      marrow chimera experiments further showed that circulating CCR7(+) leukocytes
      partially rescued midterm profibrotic changes in CCR7(-/-) mice. In human
      histological sections of chronic thrombosed femoral veins, CCR7(+) cells were
      present in the fibrotic areas. CONCLUSIONS: Post-thrombotic vein wall remodeling
      is impaired in CCR7(-/-) mice, with a profibrotic phenotype, is dependent on the
      thrombotic mechanism, and is mediated by circulating CCR7(+) cells. Unlike other
      postinjury fibrotic responses, CCR7(+) signaling may be important for positive
      vein wall remodeling after VT.

PMID- 24311384
TI  - Long-term outcome following percutaneous coronary intervention with drug-eluting
      stents compared with bare-metal stents in saphenous vein graft lesions: from
      Western Denmark Heart Registry.
AB  - OBJECTIVES: We used the Western Denmark Heart Registry to assess one-year and
      long-term all-cause mortality and stent failure following Percutaneous Coronary
      Intervention (PCI) with drug-eluting stents (DES) or bare-metal stents (BMS).
      BACKGROUND: The use of DES compared with BMS during PCI has reduced the risk of
      restenosis in native coronary artery lesions. In saphenous vein grafts (SVG) the
      outcome after DES compared with BMS is insufficiently described. METHODS: From
      January 1, 2002 to December 31, 2010 all patients with PCI of SVG lesions were
      identified among 3.0 million inhabitants. Stent failure was defined as clinically
      driven target lesion revascularization, graft occlusion without intervention, or
      stent thrombosis. RESULTS: The study cohort consisted of 529 patients with 755
      SVG lesions (348 DES patients with 510 lesions and 181 BMS patients with 245
      lesions). Mean age did not differ between patients with DES-treated lesions
      compared to patients with BMS-treated lesions (67.5 +/- 9.1 years vs. 67.6 +/-
      9.3 years; P = 0.85). The median follow-up time was 3.0 years (25th-75th
      percentile: 1.4-5.1 years). One-year (n = 27 (8.2%) vs. n = 12 (6.7%), log rank P
      = 0.60) and 3-year cumulative mortality (n = 31 (18.8%) vs. n = 59 (21.8%), log
      rank P = 0.64) did not differ significantly between DES- and BMS-treated
      patients. One-year cumulative stent failure was seen in 39 (6.6%) DES-treated
      lesions vs. 24 (10.8%) BMS-treated lesions (P = 0.088), and 3-year cumulative
      stent failure in 48 (15.4%) vs. 34 (18.8%) lesions (P = 0.25), respectively.
      CONCLUSION: In SVG lesions, DES showed no long-term benefit compared to BMS in
      rates of all-cause mortality or stent failure.

PMID- 24311385
TI  - Compound heterozygous deletions in pseudoautosomal region 1 in an infant with
      mild manifestations of langer mesomelic dysplasia.
AB  - Haploinsufficiency of SHOX on the short arm pseudoautosomal region (PAR1) leads
      to Leri-Weill dyschondrosteosis (LWD), and nullizygosity of SHOX results in
      Langer mesomelic dysplasia (LMD). Molecular defects of LWD/LMD include various
      microdeletions in PAR1 that involve exons and/or the putative upstream or
      downstream enhancer regions of SHOX, as well as several intragenic mutations.
      Here, we report on a Japanese male infant with mild manifestations of LMD and
      hitherto unreported microdeletions in PAR1. Clinical analysis revealed mesomelic
      short stature with various radiological findings indicative of LMD. Molecular
      analyses identified compound heterozygous deletions, that is, a maternally
      inherited ~46 kb deletion involving the upstream region and exons 1-5 of SHOX,
      and a paternally inherited ~500 kb deletion started from a position ~300 kb
      downstream from SHOX. In silico analysis revealed that the downstream deletion
      did not affect the known putative enhancer regions of SHOX, although it
      encompassed several non-coding elements which were well conserved among various
      species with SHOX orthologs. These results provide the possibility of the
      presence of a novel enhancer for SHOX in the genomic region ~300 to ~800 kb
      downstream of the start codon.

PMID- 24311386
TI  - Exploring resource use and associated costs in end-of-life care for older people
      with dementia in residential care homes.
AB  - OBJECTIVE: The goals of this study are to describe end-of-life care costs of
      older people with dementia (OPWD) residents in care homes (CHs) with no on-site
      nursing and evaluate the economic case for an intervention designed to improve
      end-of-life care for OPWD in CHs. METHODS: Phase 1 tracked for a year, from March
      2009, health services received by 133 OPWD in six residential CHs in the East of
      England. CH and resident characteristics were obtained through standardised
      assessment tools, interviews with CH managers and publicly available information
      from the independent regulator of social care services in England. Phase 2 used a
      modified Appreciative Inquiry intervention that ran for 6 months from January
      2011, in three of the six CHs. Wilcoxon matched-pairs sign-rank tests were
      conducted to compare total cost and cost components during Phases 1 and 2 for
      those residents who had participated in both. RESULTS: Costs for each resident in
      Phase 1 were about L2800 per month, including service, accommodation and
      medication. Resource use was associated with resident characteristics. The
      intervention was perceived as having a positive impact on working relationships
      between CHs and visiting health care practitioners. Following the intervention
      total service costs fell by 43%. Hospital care costs fell by 88%. CONCLUSIONS:
      Results presented here represent early work in an under-researched area of care.
      Appreciative Inquiry appears to improve and change working relationships with
      promising outcomes, but more research is needed to test these findings further
      with larger samples and more robust controls.

PMID- 24311387
TI  - Isolation and purification of recombinant human plasminogen Kringle 5 by liquid
      chromatography and ammonium sulfate salting-out.
AB  - In this work, a novel method was established to isolate and purify Human
      plasminogen Kringle 5 (HPK5) as a histidine-tagged fusion protein expressed in
      Escherichia coli BL21 (DE3). This method consisted of sample extraction using a
      Ni-chelated Sepharose Fast-Flow affinity column, ammonium sulfate salting-out and
      Sephadex G-75 size-exclusion column in turn. The purity analysis by SDS-PAGE,
      high-performance size-exclusion and reversed-phase chromatographies showed that
      the obtained recombinant fusion HPK5 was homogeneous and its purity was higher
      than 96%; the activity analysis by chorioallantoic membrane model of chicken
      embryos revealed that the purified recombinant HPK5 exhibited an obvious anti
      angiogenic activity under the effective range of 5.0-25.0 ug/mL. Through this
      procedure, about 19 mg purified recombinant fusion HPK5 can be obtained from 1 L
      of original fermentation solution. Approximate 32% of the total recombinant
      fusion HPK5 can be captured and the total yield was approximately 11%.

PMID- 24311388
TI  - An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi
      syndrome.
AB  - Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by an
      abnormality on the long arm of chromosome 15 (q11-q13) that results in a host of
      behavioral characteristics including excessive interest in food, skin picking,
      difficulty with a change in routine, and obsessive and compulsive behaviors. Skin
      picking can result in serious and potentially life-threatening infections. Recent
      evidence suggests that the excitatory neurotransmitter glutamate is dysregulated
      in obsessive-compulsive behaviors, and modulation of the glutaminergic pathway
      may decrease compulsive behaviors, such as recurrent hair pulling or skin-picking
      behaviors. N-acetylcysteine (NAC), a derivative of the amino acid cysteine, is
      thought to act either via modulation of NMDA glutamate receptors or by increasing
      glutathione in pilot studies. Thirty-five individuals with confirmed PWS (ages 5
      39 years, 23 females/12 males) and skin-picking behavior for more than 1 year
      were treated with N-acetylcysteine (Pharma-NAC(r)) at a dose of 450-1,200 mg/day.
      Skin-picking symptoms and open lesions were assessed after 12 weeks of treatment
      by counting and measuring lesions before and after the medication. All 35
      individuals had improvement in skin-picking behaviors. Ten (29%) individuals (six
      males and four females) did not have complete resolution of skin-picking
      behavior, but had significant reduction in the number of active lesions. Longer
      term, placebo-controlled trials are needed to further assess the potential
      benefit of this treatment.

PMID- 24311389
TI  - Hydroxypropyl-sulfobutyl-beta-cyclodextrin improves the oral bioavailability of
      edaravone by modulating drug efflux pump of enterocytes.
AB  - The objective of the study was to evaluate the effect of hydroxypropyl-sulfobutyl
      beta-cyclodextrin (HP-SBE-betaCD) on the bioavailability and intestinal
      absorption of edaravone, and identify its mechanism of action. We devised HP-SBE
      betaCD as a carrier and modulator of P-glycoprotein (Pgp) efflux pump, and
      edaravone as a model drug, and prepared edaravone/HP-SBE-betaCD inclusion
      complex. HP-SBE-betaCD improved the water solubility and enhanced the
      bioavailability of edaravone by 10.3-fold in rats. Then, in situ single-pass
      intestinal perfusion showed that HP-SBE-betaCD had an effect of improving the
      permeability and inhibiting the efflux of edaravone. Furthermore, the effects of
      HP-SBE-betaCD on Pgp were achieved through interfering with the lipid raft and
      depleting the cholesterol of enterocytes membrane. From the results, we presented
      the novel mechanisms. First, edaravone/HP-SBE-betaCD had a lower release from the
      inclusion compound to protect edaravone from the low pH of the stomach. Then, HP
      SBE-betaCD modulated the membrane microenvironment of intestinal absorption
      epithelial cells. At last, the result was that HP-SBE-betaCD enhanced the
      absorption of edaravone by interfering with Pgp. In conclusion, HP-SBE-betaCD
      improves the bioavailability of drug not only because of its enhancing water
      solubility of the drug, but also because it modulates the Pgp-mediated efflux
      from enterocytes.

PMID- 24311391
TI  - Tumor growth attenuating effects of naringenin.

PMID- 24311390
TI  - Pass the popcorn: "obesogenic" behaviors and stigma in children's movies.
AB  - OBJECTIVE: To determine the prevalence of obesity-related behaviors and attitudes
      in children's movies. METHODS: A mixed-methods study of the top-grossing G- and
      PG-rated movies, 2006-2010 (4 per year) was performed. For each 10-min movie
      segment, the following were assessed: 1) prevalence of key nutrition and physical
      activity behaviors corresponding to the American Academy of Pediatrics obesity
      prevention recommendations for families; 2) prevalence of weight stigma; 3)
      assessment as healthy, unhealthy, or neutral; 3) free-text interpretations of
      stigma. RESULTS: Agreement between coders was >85% (Cohen's kappa = 0.7), good
      for binary responses. Segments with food depicted: exaggerated portion size
      (26%); unhealthy snacks (51%); sugar-sweetened beverages (19%). Screen time was
      also prevalent (40% of movies showed television; 35% computer; 20% video games).
      Unhealthy segments outnumbered healthy segments 2:1. Most (70%) of the movies
      included weight-related stigmatizing content (e.g., "That fat butt! Flabby arms!
      And this ridiculous belly!"). CONCLUSIONS: These popular children's movies had
      significant "obesogenic" content, and most contained weight-based stigma. They
      present a mixed message to children, promoting unhealthy behaviors while
      stigmatizing the behaviors' possible effects. Further research is needed to
      determine the effects of such messages on children.

PMID- 24311392
TI  - Pacesetters and pathfinders: an interview with Amy S. Peele, RN.

PMID- 24311393
TI  - Kidney transplant and the digital divide: is information and communication
      technology a barrier or a bridge to transplant for African Americans?
AB  - CONTEXT: Barriers to kidney transplant for African Americans are well documented
      in the literature. Little information on ownership of information and
      communication technology and use of such technology in transplant populations has
      been published. OBJECTIVE: To characterize racial differences related to
      ownership and use of information and communication technology in kidney
      transplant patients. DESIGN: A single-center, cross-sectional survey study.
      SETTING: An urban Midwestern transplant center. PARTICIPANTS: 78 pretransplant
      patients and 177 transplant recipients. MAIN OUTCOMES MEASURES: The survey
      consisted of 6 demographic questions, 3 disease-related questions, and 9
      technology-related questions. Dichotomous (yes/no) and Likert-scale items were
      the basis for the survey. RESULTS: Cell phone use was high and comparable between
      groups (94% in African Americans, 90% in whites, P= .22). A vast majority (75% of
      African Americans and 74% of whites) reported being "comfortable" sending and
      receiving text messages. Computer ownership (94.3% vs 79.3%) and Internet access
      (97.7% vs 80.7%) were greater among whites than African Americans (both P< .01).
      Fewer African Americans were frequent users of the Internet (27.1% vs 56.3%) and
      e-mail (61.6% vs 79.3%) than whites (both P<.01). More African Americans than
      whites preferred education in a classroom setting (77% vs 60%; P< .005) and
      educational DVDs (66% vs 46%; P< .002). CONCLUSION: The use of cell phone
      technology and text messaging was ubiquitous and comparable between groups, but
      computer and Internet access and frequency of use were not. Reaching out to the
      African American community may best be accomplished by using cell phone/text
      messaging as opposed to Internet-based platforms.

PMID- 24311394
TI  - The Alcohol Relapse Risk Assessment: a scoring system to predict the risk of
      relapse to any alcohol use after liver transplant.
AB  - CONTEXT: Alcohol relapse after liver transplant heightens concern about recurrent
      disease, nonadherence to the immunosuppression regimen, and death. OBJECTIVES: To
      develop a scoring system to stratify risk of alcohol relapse after liver
      transplant. DESIGN: Retrospective medical record review. SETTING AND
      PARTICIPANTS: All adult liver transplants performed from May 2002 to February
      2011 at a single center in the United States. MAIN OUTCOME MEASURE: The incidence
      of return to any alcohol consumption after liver transplant. RESULTS: Thirty-four
      percent (40/118) of patients with a history of alcohol abuse/dependency relapsed
      to use of any alcohol after liver transplant. Nine of 25 hypothesized risk
      factors were predictive of alcohol relapse after liver transplant: absence of
      hepatocellular carcinoma, tobacco dependence, continued alcohol use after liver
      disease diagnosis, low motivation for alcohol treatment, poor stress management
      skills, no rehabilitation relationship, limited social support, lack of
      nonmedical behavioral consequences, and continued engagement in social activities
      with alcohol present. Each independent predictor was assigned an Alcohol Relapse
      Risk Assessment (ARRA) risk value of 1 point, and patients were classified into 1
      of 4 groups by ARRA score: ARRA I = 0, ARRA II = 1 to 3, ARRA III = 4 to 6, and
      ARRA IV = 7 to 9. Patients in the 2 higher ARRA classifications had significantly
      higher rates of alcohol relapse and were more likely to return to pretransplant
      levels of drinking. CONCLUSION: Alcohol relapse rates are moderately high after
      liver transplant. The ARRA is a valid and practical tool for identifying
      pretransplant patients with alcohol abuse or dependency at elevated risk of any
      alcohol use after liver transplant.

PMID- 24311396
TI  - Compassion fatigue in liver and kidney transplant nurse coordinators: a
      descriptive research study.
AB  - CONTEXT: Because of the nature of the helping professions, nurses are at high
      risk for compassion fatigue and burnout. In the past, many researchers have
      studied compassion fatigue and burnout in nurses. However, reports of research
      assessing liver and kidney transplant nurse coordinators' compassion fatigue and
      burnout are rare. OBJECTIVE: To assess liver and kidney transplant nurse
      coordinators' levels of compassion fatigue and burnout. DESIGN: A
      nonexperimental, exploratory descriptive study was conducted using the
      Professional Quality of Life Scale Version 5 (ProQOL-V), a 30-item self-report
      instrument to measure participants' level of compassion satisfaction, burnout,
      and secondary traumatic stress. SETTING AND PARTICIPANTS: This study sampled 14
      liver and kidney transplant nurse coordinators from a large multiorgan transplant
      center in the Southeast region. RESULTS: Transplant nurse coordinators had an
      average level of compassion satisfaction, an average level of burnout, and an
      average level of secondary traumatic stress. Within liver and kidney transplant
      nurse coordinators, a statistically significant relationship was found between
      education levels of transplant nurse coordinators and the level of burnout,
      suggesting that education levels may influence burnout.

PMID- 24311397
TI  - Assessing respiratory therapists' awareness of the organ donor referral criteria
      and attitudes toward organ donation.
AB  - CONTEXT: Respiratory therapists provide care for every potential organ donor but
      do not receive formal education regarding organ procurement. OBJECTIVE: To assess
      the number of respiratory therapists who are aware of the organ donor referral
      criteria and their attitude toward organ donation before and after an organ
      procurement organization provided an educational course. DESIGN: A retrospective
      analysis of surveys following an educational course. SETTING: Hospital
      respiratory therapy departments within the Texas Organ Sharing Alliance northern
      region.Participants-Respiratory therapists who attended the educational course.
      MAIN OUTCOME MEASURE(S): Measured outcomes were respiratory therapists' attitude
      scores before and after the organ procurement organization provided the
      educational course, the number of organ donor cases experienced during the
      respiratory therapists' careers, the unit(s) of the hospital in which the
      respiratory therapists worked, and the respiratory therapists' awareness of the
      organ donor referral criteria before the organ procurement organization provided
      the educational course. RESULTS: Seventy-seven respiratory therapists were
      surveyed. Sixty-two respiratory therapists identified themselves as working in a
      critical care setting and 58% stated they were unaware of the donor referral
      criteria. Seventeen respiratory therapists reported their attitude toward organ
      donation improved with no perception decline. Using the Wilcoxon signed rank test
      for statistical analysis, the mean attitude score after the education course was
      significantly different at an alpha level of 0.05 (P<.01) than the mean attitude
      score before the course. After the program, 98.7% of the respiratory therapists
      stated they would begin evaluating patients regarding the organ donor referral
      criteria before extubation.

PMID- 24311395
TI  - Patient-reported immunosuppression nonadherence 6 to 24 months after liver
      transplant: association with pretransplant psychosocial factors and perceptions
      of health status change.
AB  - CONTEXT: Knowing the prevalence and risk factors of immunosuppression
      nonadherence after liver transplant may help guide intervention development.
      OBJECTIVE: To examine whether sociodemographic and psychosocial variables before
      liver transplant are predictive of nonadherence after liver transplant. DESIGN:
      Structured telephone interviews were used to collect self-report
      immunosuppression adherence and health status information. Medical record reviews
      were then completed to retrospectively examine the relationship between
      immunosuppression adherence and pretransplant variables, including
      sociodemographic and medical characteristics and the presence or absence of 6
      hypothesized psychosocial risk factors. SETTING AND PARTICIPANTS: A
      nonprobability sample of 236 adults 6 to 24 months after liver transplant at 2
      centers completed structured telephone interviews. MAIN OUTCOME MEASURE:
      Immunosuppressant medication nonadherence, categorized as missed-dose and altered
      dose "adherent" or "nonadherent" during the past 6 months; immunosuppression
      medication holidays. RESULTS: Eighty-two patients (35%) were missed-dose
      nonadherent and 34 patients (14%) were altered-dose nonadherent. Seventy-one
      patients (30%) reported 1 or more 24-hour immunosuppression holidays in the past
      6 months. Missed-dose nonadherence was predicted by male sex (odds ratio, 2.46;
      P= .01), longer time since liver transplant (odds ratio, 1.08; P= .01),
      pretransplant mood disorder (odds ratio, 2.52; P=.004), and pretransplant social
      support instability (odds ratio, 2.25; P=.03). Altered-dose nonadherence was
      predicted by pretransplant mood disorder (odds ratio, 2.15; P= .04) and
      pretransplant social support instability (odds ratio, 1.89; P= .03). CONCLUSION:
      Rates of immunosuppressant nonadherence and drug holidays in the first 2 years
      after liver transplant are unacceptably high. Pretransplant mood disorder and
      social support instability increase the risk of nonadherence, and interventions
      should target these modifiable risk factors.

PMID- 24311398
TI  - Contact between deceased donors' families and organ recipients.
AB  - The benefits and disadvantages of posttransplant contact between a donor family
      and the organ recipient are disputed. In this study far more contacters reported
      benefits rather than disadvantages and noncontacters reported the opposite. The
      dissatisfaction of noncontacters with no contact was high: no less than 60%
      wanted some form of contact in the future. The authors conclude that contact has
      more benefits for the donor family than disadvantages, evidenced by families'
      desire to maintain contact with the organ recipient. Both donor families and
      organ recipients need the transplant coordinator's initiative and guidance on
      this issue. 

PMID- 24311399
TI  - Reducing liver transplant length of stay: a Lean Six Sigma approach.
AB  - CONTEXT: Organ transplant centers are under increasing scrutiny to maintain
      outcomes while controlling cost in a challenging population of patients.
      Throughout health care and transplant specifically, length of stay is used as a
      benchmark for both quality and resource utilization. OBJECTIVE: To decrease our
      length of stay for liver transplant by using Lean Six Sigma methods. DESIGN: The
      Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) method was used to
      systematically analyze our process from transplant listing to hospital discharge
      after transplant, identifying many factors affecting length of stay. PATIENTS OR
      OTHER PARTICIPANTS: Adult, single-organ, primary liver transplant recipients
      between July 2008 and June 2012 were included in the study. Recipients with
      living donors or fulminant liver failure were excluded. INTERVENTION(S): Multiple
      interventions, including a clinical pathway and enhanced communication, were
      implemented. MAIN OUTCOME MEASURE(S): Length of stay after liver transplant and
      readmission after liver transplant.R ESULTS: Median length of stay decreased
      significantly from 11 days before the intervention to 8 days after the
      intervention. Readmission rate did not change throughout the study. The improved
      length of stay was maintained for 24 months after the study. CONCLUSION: Using a
      Lean Six Sigma approach, we were able to significantly decrease the length of
      stay of liver transplant patients. These results brought our center's outcomes in
      accordance with our goal and industry benchmark of 8 days. Clear expectations,
      improved teamwork, and a multidisciplinary clinical pathway were key elements in
      achieving and maintaining these gains.

PMID- 24311400
TI  - Hypercalcemia due to giant cell myocarditis: a case report.
AB  - Granulomatous diseases are a rare cause of hypercalcemia. The pathogenesis is
      presumed to be from endogenous production of 1,25-dihydroxyvitamin D by activated
      macrophages in granulomatous lesions, which harbor the 1alpha-hydroxylase enzyme.
      Herein the first case of hypercalcemia associated with giant cell myocarditis, an
      unusual type of granulomatous process, is reported. In this case, a patient with
      giant cell myocarditis had development of progressive heart failure and
      cardiorenal syndrome that required biventricular support. One year later,
      hypercalcemia associated with a relatively high 1,25-vitamin D level and a
      concomitantly suppressed parathyroid hormone level developed in the presence of
      stage 4 chronic kidney disease. Her other workup of hypercalcemia was unrevealing
      for vitamin D intoxication and multiple myeloma. Computed tomography of her chest
      showed no signs of hilar lymphadenopathy. Her calcium levels returned to normal
      with low-dose steroid therapy and have remained normal following a successful
      heart transplant. This case illustrates an unusual cause of hypercalcemia thought
      to be due to extrarenal calcitriol production associated with giant cell
      myocarditis. 

PMID- 24311401
TI  - Intestinal retransplant in a patient after fungal sepsis: considerations and
      issues.
AB  - An adolescent female received an isolated intestinal transplant. She developed
      severe exfoliative rejection and required complete enterectomy. The patient
      developed a septic hip and lung lesions with biopsy-proven Aspergillus nidulans
      and was treated with caspofungin, ambiosome, and voriconizole. After completing a
      year of treatment and extensive physical therapy, the patient requested
      retransplant. The case was presented to the ethics committee, which determined
      that the patient demonstrated understanding of the risks and benefits. Infectious
      disease consultants presented data showing high risk for fungal recurrence.
      Quality of life as observed by our transplant team seemed good and the patient
      had no other indications. Retransplant is associated with higher risk than first
      transplants. Does the team have the right to deny retransplant if the competent
      patient requests transplant despite high risk? Guidelines for this indication are
      complex and evolving. 

PMID- 24311402
TI  - Orthotopic heart transplant for treatment-resistant cardiomyopathy in Kawasaki
      syndrome: report of a successful case.
AB  - Kawasaki disease is a systemic vascular inflammatory disorder of yet unknown
      cause that is associated with critical cardiovascular complications. Several long
      term medical therapies, coronary revascularization, and heart transplant have
      been introduced to treat coronary artery lesions. This report describes a 20-year
      old man with Kawasaki disease manifesting as intermittent chest pain and nausea
      who had advanced decompensated cardiomyopathy (ejection fraction, 15%) diagnosed.
      Coronary artery bypass surgery and implantation of a cardioverter defibrillator
      had been performed, although no significant clinical improvement was observed.
      Finally, a successful orthotopic bicaval heart transplant was performed. Follow
      up examination after 1 year revealed normal cardiac function with no evidence of
      organ rejection. This experience demonstrated that heart transplant might be a
      successful method of treating permanent ischemic cardiomyopathy in patients with
      Kawasaki syndrome. 

PMID- 24311404
TI  - Perspectives on abdominal organ preservation solutions: a comparative literature
      review.
AB  - Various preservation solutions are used for kidney, liver, pancreas, small
      intestine, and multiorgan recoveries and transplants. The effectiveness of these
      solutions, primarily measured by ability to preserve the organ and graft
      survival, was analyzed. The 2 most common solutions used for intra-abdominal
      organs are University of Wisconsin Solution (UW)/Viaspan and Histidine-tryptophan
      ketoglutarate (HTK)/Custodiol solution. Outcomes for liver, pancreas, and kidney
      allografts preserved with these 2 solutions are similar. Although HTK solution
      shows conflicting results with respect to pancreatic cellular edema, researchers
      in several studies have noted that HTK solution may be more protective than UW
      solution against biliary complications in liver transplant. In kidney recoveries,
      HTK solution may be associated with higher graft loss and increased delayed graft
      function in marginal deceased donors but had lower incidence of delayed graft
      function in living donors when compared with UW. UW remains the reference
      standard for use during multiorgan recoveries but is experiencing strong
      competition from HTK and other alternative solutions. Some researchers suggest
      that Celsior's comparable results in abdominal organs and viability for thoracic
      organs makes it a strong competitor, especially in multiorgan recoveries. Each
      solution has benefits accompanied by disadvantages. Although it may not be
      feasible, when considering single-organ recoveries, consideration of alternative
      solutions may be warranted. 

PMID- 24311403
TI  - Randomized trial to evaluate nutritional status and absorption of enteral feeding
      after brain death.
AB  - CONTEXT: Catecholamines and inflammatory mediators, with elevated levels after
      brain death, are associated with reduced function and survival of transplanted
      organs. Enteral nutrition reduces tissue damage and may benefit organs.
      OBJECTIVE: To evaluate the effects of immunomodulating enteral nutrition in organ
      donors. DESIGN: Prospective, randomized, open-label study. SETTING: Intensive
      care unit. PATIENTS: Thirty-six brain-dead organ donors. INTERVENTIONS: Donors
      were randomized to receive enteral nutrition containing omega-3 polyunsaturated
      fatty acid, antioxidants, and glutamine or standard care (fasting). Donors
      received hormonal replacement therapy of corticosteroid, levothyroxine, dextrose,
      and insulin. MAIN OUTCOME MEASURES: Gastrointestinal assimilation (measured by 13
      carbon-labeled uracil breath analysis), quantity of organs recovered, resting
      energy expenditure, urine level of urea nitrogen, and serum levels of albumin,
      prealbumin, interleukin 6, tumor necrosis factor-alpha, and C-reactive protein
      were evaluated. RESULTS: Thirteen patients (36%) assimilated 13C-labeled uracil.
      Resting energy expenditure was significantly higher than predicted between 10 and
      14 hours after baseline in 33 donors (P= .007). Other measures were not
      conclusively different between fed and fasting groups. No adverse events occurred
      that were related to the enteral feeding. CONCLUSIONS: About 30% of donors
      metabolized 13C-labeled uracil, although no difference in oxidation rate was
      found between fasting and fed donors. Corticosteroid administration lowers plasma
      levels of interleukin 6 and most likely contributes to greater than predicted
      resting energy expenditure. Thus energy needs may not be met during fasting if
      hormones are given. Consequences of this possible energy deficit warrant further
      study.

PMID- 24311405
TI  - Validation and adaptation of the Modified Transplant Symptom Occurrence and
      Symptom Distress Scale-59 Items Revised into Turkish.
AB  - CONTEXT: The Modified Transplant Symptom Occurrence and Symptom Distress Scale-59
      Items Revised (MTSOSD-59R) is a validated self-reported scale assessing patients'
      subjective experiences of adverse effects of immunosuppressants. It has been
      reported that the scale should be adapted and validated before it is used in
      patients of a different cultural (Brazilian, Dutch, German, French, Hindi,
      Italian, Spanish, and Swedish) background. OBJECTIVE: To validate and adapt the
      MTSOSD-59R for use in Turkish transplant recipients. MATERIALS AND METHODS: This
      cross-sectional study was performed between March 2010 and February 2011, and
      included 180 liver and kidney transplant recipients treated in 2 university
      hospitals in western Turkey. In addition, 180 healthy control participants were
      recruited from a community health service. Data were collected by using a
      demographic and clinical characteristics scale (MTSOSD-59R) and the Beck
      Depression Inventory. Items were translated in a culturally sensitive way by
      using forward-backward translation. Content validity was evaluated by using the
      content validity index. Ridit analysis and descriptive statistics helped to
      describe symptom experience in our population, and Mann Whitney U testing was
      used to compare patients versus healthy controls, depressed versus nondepressed
      patients, and male versus female patients for validity purposes. Split-half
      reliability analysis was used. RESULTS: The content validity index was perfect
      (ie, value 1.0); the Turkish translation of the MTSOSD-59R had excellent known
      group validity. Split-half Spearman Brown corrected reliability coefficient was
      0.991 for symptom occurrence and 0.992 for symptom distress. CONCLUSION: The
      results suggest that the Turkish scale has appropriate language, content, and
      construct validity. This scale can now be used to assess the symptom experience
      related to immunosuppressive therapy in Turkish organ transplant recipients.

PMID- 24311406
TI  - Hydrogen-bonding in aminocatalysis: from proline and beyond.
AB  - This Concept article summarizes recent progress in the field of hydrogen-bonding
      aminocatalysis using proline-derived systems. The aminocatalysts available in the
      literature are categorized by the incorporated hydrogen-bonding scaffold and its
      mode of recognition. Both mono- and double-hydrogen-bonding motifs are discussed
      and examples of their application in asymmetric synthesis are given. 

PMID- 24311407
TI  - Four patients with Sillence type I osteogenesis imperfecta and mild bone
      fragility, complicated by left ventricular cardiac valvular disease and cardiac
      tissue fragility caused by type I collagen mutations.
AB  - Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue
      (HDCT) characterized by blue or gray sclerae, variable short stature,
      dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We
      present four examples of OI type I complicated by valvular heart disease and
      associated with tissue fragility. The diagnosis of a type I collagen disorder was
      confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was
      investigated with electrophoresis of collagens from cultured skin fibroblasts,
      showing structurally abnormal collagen type I, skin biopsy showed unusual
      histology and abnormal collagen fibril ultra-structure at electron microscopy.
      The combined clinical, surgical, histological, ultra-structural, and molecular
      genetic data suggest the type I collagen defect as contributory to cardiac
      valvular disease. The degree of tissue fragility experienced at cardiac surgery
      in these individuals, also reported in a small number of similar case reports,
      suggests that patients with OI type I need careful pre-operative assessment and
      consideration of the risks and benefits of cardiac surgery.

PMID- 24311408
TI  - Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer
      progression.
AB  - INTRODUCTION: Prostate cancer is the second leading cause of cancer-related death
      among men in North America. While a majority of prostate cancer cases remain
      indolent, subsets of patients develop aggressive cancers, which may lead to
      death. The current methods of detection include digital rectal examination and
      the serum PSA test. However, due to lack of specificity, neither of these
      approaches is able to accurately discriminate between indolent and aggressive
      cancer, which is why there is a need for additional prognostic factors.
      Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1,
      to be elevated in aggressive prostate cancer. METHODS: In the current study, we
      assessed the diagnostic and prognostic potential of ACAT1 by analyzing its
      expression using immunohistochemistry on a tissue microarray consisting of 251
      clinically localized prostate cancer patients who have undergone radical
      prostatectomy. RESULTS: Using quantitative digital imaging software, we found
      that ACAT1 expression was significantly greater in cancerous cores compared to
      adjacent benign cores (P < 0.0001), in Gleason score (GS) >=8 cancers versus
      GS<=6 cancers (P < 0.0001), GS>=8 cancers versus GS7 cancers (P = 0.001), as well
      as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted
      biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and
      multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre
      operative PSA level, Gleason score and pathological stage. In univariate time-to
      recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases
      (P = 0.0025), whereas ERG positive cases did not display any differences.
      DISCUSSION: Taken together, these findings indicate that ACAT1 expression could
      serve as a potential prognostic marker in prostate cancer, specifically in
      differentiating indolent and aggressive forms of cancer.

PMID- 24311409
TI  - Orbital apex syndrome secondary to granulomatosis with polyangiitis.
AB  - Orbital apex syndrome (OAS) is an optic nerve dysfunction with palsy of the
      third, fourth and sixth cranial nerves and ophthalmic division of the fifth
      cranial nerve. Causes can be infective, inflammatory, traumatic, neoplastic or
      vasculitic. We describe the first case in British literature and second worldwide
      of OAS presenting as granulomatosis with polyangiitis (GPA). A 38-year-old
      patient presented with left periorbital swelling and pain. An examination
      revealed left eye proptosis, tenderness in the ophthalmic distribution of the
      trigeminal nerve, unilateral ophthalmoplegia and reduced visual acuity. Initial
      treatment included intravenous antibiotics, steroids and nasal
      decongestants.Imaging demonstrated sinusitis and a suspected abscess from the
      infratemporal fossa to the orbital apex. However, sinus surgery showed
      granulation tissue without pus. The biopsy result was highly suggestive of GPA. A
      subsequent vasculitic screen was cytoplasmic-antineutrophil cytoplasmic antibody
      positive.This case highlights an unusual presentation of OAS secondary to GPA, as
      initial features suggested an infective cause. 

PMID- 24311410
TI  - Oral health management of a patient with 47,XYY syndrome.
AB  - The 47,XYY syndrome is an aneuploidy (abnormal number) of sex chromosomes, where
      a human male receives an extra Y chromosome, making 47 chromosomes instead of the
      usual 46. Individuals with 47,XYY are usually physically normal and tend to be
      tall and thin. They are not at increased risk of mental retardation and
      cardiovascular diseases. They may have speech delay, hyperactivity and
      normal/decreased IQ level. Behavioural problems are not common in 47,XYY
      individuals. There have been reports that suggest the tooth-size increase in
      47,XYY males is due to a direct genetic effect. The patient presented with
      multiple over-retained deciduous, unerupted permanent teeth and increased
      incidence of carious lesions may be attributed to decreased oral hygiene
      maintenance. The present article describes the medical and dental history along
      with the clinical management of oral health issues in an 18-year-old male patient
      with 47,XYY syndrome having normal physical structure and development. 

PMID- 24311411
TI  - Penile metastases treated with partial glansectomy and adjuvant radiotherapy 5
      years after an initial diagnosis of rectal cancer.
AB  - A 61-year-old man with recurrent rectal carcinoma was referred to the urology
      clinic with two penile lesions. These had negatively affected his quality of life
      and he underwent a radical circumcision and proximal glansectomy with
      reconstruction. This case report examines the clinical presentation and surgical
      treatment of rectal carcinoma metastasising to the penis. 

PMID- 24311412
TI  - Brachial plexitis preceding encephalomyelitis in a patient with West Nile virus
      infection.
AB  - We describe the case of a 54-year-old woman with West Nile virus infection
      presenting with painful brachial plexitis and radiculitis that preceded the more
      typically associated symptoms of meningoencephalitis. Physicians should be aware
      that West Nile virus infection can present with painful brachial plexitis. 

PMID- 24311413
TI  - Leiomyosarcoma of the maxilla in a 24-year-old man who initially presented with
      odontalgia, and suffered from tumour mismanagement.
AB  - Leiomyosarcoma is an uncommon malignant soft tissue tumour originating from
      smooth muscle cells. It generally occurs in the female genital tract, especially
      in the uterus, gastrointestinal tract, retroperitoneum and rarely in the head and
      neck. Here we report a case of leiomyosarcoma in a 24-year-old man with a 6-month
      history of toothache and extraction of three right upper molar teeth, that was
      complicated by fistula tract formation and facial swelling. Imaging studies
      demonstrated tumoural lesions involving the right maxillary sinus, nasal cavity,
      hard palate and orbit. The histopathological and immunohistochemical studies
      confirmed that it was leiomyosarcoma. 

PMID- 24311414
TI  - Clinical course of acute chemical lung injury caused by 3-chloropentafluoropene.
AB  - Perfluoroallyl chloride (PFAC), a fluorine-containing compound, has very severe
      toxicity, but this toxicity is not well characterised. We report a fatal case of
      acute chemical lung injury caused by the inhalation of PFAC. A 39-year-old man,
      working at a chemical factory, inhaled PFAC gas and died 16 days later of acute
      lung injury with severe pneumothorax. We present his clinical course together
      with thoracic CT findings, autopsy and analysis of PFAC in blood and urine
      samples with gas chromatograph-mass spectrometry. Previously, a fatal case of
      PFAC was reported in 1981 but PFAC was not identified in any of the patient's
      samples. In our patient, we identified PFAC in both blood and urine samples. Our
      toxicological analysis may be used as a reference to detect PFAC toxicity in the
      future. Our study should be helpful for diagnosing lung injury induced by a
      highly toxic gas, such as PFAC. 

PMID- 24311415
TI  - Tacrolimus-induced encephalopathy and polyneuropathy in a renal transplant
      recipient.
AB  - Tacrolimus is an immunosuppressant frequently used following solid organ
      transplantation, including renal transplantation. Peripheral neuropathy is an
      uncommon neurological side effect of tacrolimus and has rarely been reported in
      renal transplantation. We report a patient who received a living-related donor
      kidney transplant and presented with altered mental status and new-onset
      bilateral foot drop. Laboratory tests including cerebrospinal fluid tests
      excluded infection, and MRI of the brain showed chronic microvascular ischaemic
      changes. Electromyography and nerve conduction study confirmed bilateral common
      peroneal nerve demyelination. He was also found to have inadvertently overdosed
      on tacrolimus at home. After switching from tacrolimus to cyclosporine, the
      patient's symptoms improved within 5 months. His renal function was maintained
      with an immunosuppressant regimen of cyclosporine, prednisone and mycophenolic
      acid. The prompt recognition of tacrolimus as a potential neurotoxic drug in a
      patient with renal transplant and substituting tacrolimus with a different
      immunosuppressant may prevent permanent neurological damage. 

PMID- 24311416
TI  - An unusual association between acute ischaemic stroke and cerebral venous
      thrombosis with thyrotoxic state.
AB  - Arterial cerebral ischaemia has been described in different diseases of the
      thyroid. Likewise, cerebral venous thrombosis (CVT) has been reported in
      association with hyperthyroidism. However, the association of arterial and venous
      cerebral ischaemic events in patients with hyperthyroidism has not been
      previously described. We report the case of a patient with thyrotoxicosis who
      presented initially with an arterial ischaemic stroke complicated by a
      concomitant CVT, ultimately treated with decompressive craniectomy. Laboratory
      results revealed elevated factor VIII coagulant activity and a positive lupus
      anticoagulant IgG. In conclusion, CVT and arterial ischaemic events can happen
      concomitantly in patients with hyperthyroidism. Although there is insufficient
      evidence to prove that a hypercoagulability state in hyperthyroidism predisposes
      to cerebral ischaemia, the presence of antiphospholipid antibodies and other
      hypercoagulability studies should be performed in patients with thyrotoxicosis
      and ischaemic events. 

PMID- 24311417
TI  - Multiple Lambl's excrescences with subvalvular extension, a rare cause of
      cryptogenic stroke: treated by port-access cardiac surgery.
AB  - A young male patient was evaluated for a cardiac cause of ischaemic stroke. In
      the work-up, a tumour was detected on the subvalvular apparatus of the mitral
      valve for which operative removal was scheduled. A port-access procedure was
      applied as a novel way of treatment. On thoracoscopic intracardiac inspection,
      however, multiple tumours were seen attached to the chordae tendineae and to the
      anterior leaflet of the mitral valve. It was decided to not to perform a plasty
      but to remove the valve in toto and insert a mechanical valve prosthesis. The
      tumours were diagnosed as multiple giant Lambl's excrescences. 

PMID- 24311418
TI  - Schneiderian papilloma of the temporal bone.
AB  - Temporal bone Schneiderian papilloma may present as a primary tumour originating
      from the middle ear and mastoid process, or an extension from sinonasal disease.
      Both forms are rare, this being only the 18th case of primary temporal bone
      Schneiderian papilloma described to date. Although the current patient has
      remained disease free after excision of the papilloma, the reported recurrence
      rate is high, comparable to sinonasal Schneiderian papilloma with extrasinus
      extension. Malignant progression of primary Schneiderian papillomas is
      significantly reduced as compared to Schneiderian papillomas that extend from the
      sinonasal tract into the temporal bone. A positive human papilloma virus status,
      as found in this case, is a common feature and prognostic factor of sinonasal
      Schneiderian papilloma but an infrequent finding in temporal bone disease. Owing
      to the high recurrence rate, the risk of malignant progression and the absence of
      reliable prognostic markers, stringent follow-up consisting of otoscopy,
      nasendoscopy and imaging is essential. 

PMID- 24311419
TI  - Intractable glaucoma necessitating dexamethasone implant (Ozurdex) removal and
      glaucoma surgery in a child with uveitis.
AB  - Although there are encouraging reports showing the use of dexamethasone implant
      (Ozurdex) in uveitis in adults, the literature is scanty regarding its benefits
      and side effects in children. A 12-year-old boy presented with intermediate
      uveitis with disc oedema. He had 20/20 visual acuity and intraocular pressure
      (IOP) of 18 mm Hg in both eyes. He was treated with intravitreal Ozurdex in his
      left eye (LE) due to progressive worsening of uveitis and disc oedema. He
      developed increased IOP (31 mm Hg) that could not be controlled on maximal
      antiglaucoma medications and required the removal of the Ozurdex implant at 2.5
      months. His IOP remained persistently high leading to increased cup disc ratio
      necessitating glaucoma filtration surgery (GFS). At 9 months of post-GFS follow
      up, IOP was 12 mm Hg in LE without any medication. Though dexamethasone implant
      is being increasingly used in children with uveitis, its potential risk factors
      such as intractable glaucoma should be considered. 

PMID- 24311420
TI  - Successful medical management of a Nocardia farcinica multiloculated pontine
      abscess.
AB  - A 60-year-old man on chronic corticosteroids developed diplopia, gait instability
      and facial weakness. Brain MRI revealed a multiloculated pontine lesion.
      Cerebrospinal fluid (CSF) analysis demonstrated a neutrophil-predominant
      pleocytosis with elevated protein and low glucose. CSF cultures were negative, as
      was an extensive infectious diseases evaluation. Neurosurgical intervention was
      deferred in favour of empiric antimicrobial therapy due to the lesion's
      inaccessible location. After discontinuation of therapy, the patient reported a
      severe headache. A subsequent MRI demonstrated intraventricular pus. CSF culture
      grew Nocardia farcinica. The patient received parenteral therapy followed by oral
      trimethoprim-sulfamethoxazole. At 9 months, he is symptom free. This case
      illustrates the importance of including Nocardia in the differential diagnosis of
      brainstem abscesses, especially in immunocompromised patients. The availability
      of antimicrobial agents with excellent Nocardia activity and CSF penetration may
      enable treatment of brainstem abscesses for which surgical intervention has
      traditionally been considered necessary with medical management alone. 

PMID- 24311421
TI  - Acute coronary syndrome in a patient with Eisenmenger's syndrome.
AB  - Eisenmenger's syndrome is a complex multisystem disease which occurs as a
      consequence of large left to right shunt affecting the pulmonary vasculature
      causing suprasystemic pulmonary artery pressures and subsequent right to left
      shunt. Usually Eisenmenger's syndrome is characterised by coronary artery
      dilation but coronary artery disease and occurrence of acute coronary syndrome is
      a rare association seldom described in literature. We present the case of a 33
      year-old man who presented with an anterior wall ST elevation mycocardial
      infarction and was thrombolysed. The occurrence of acute coronary event in a case
      of Eisenmenger's syndrome is a rare event and needs to be discussed and kept in
      mind by physicians and cardiologists who deal with such cases so that a high
      index of suspicion may be developed and emergent management may be possible. 

PMID- 24311422
TI  - Adult tethered cord syndrome resembling plantar fasciitis and peripheral
      neuropathy.
AB  - Adult tethered cord syndrome without spinal dysraphism is rare, and can present
      with subtle symptoms that could mimic other pathologies. As a result, timely
      diagnosis of this condition has proved to be a significant challenge. It is
      crucial for clinicians to be aware of adult tethered cord syndrome and its
      presenting symptoms in order to achieve early diagnosis and subsequent
      management. We present such a case with particular attention to the presenting
      history and examination. Following diagnosis, the patient underwent a laminectomy
      and cord untethering, resulting in significant improvement to his symptoms. 

PMID- 24311423
TI  - Cerebral-autoregulatory dysfunction syndrome.
AB  - Reversible cerebral vasoconstriction syndrome and reversible posterior
      leukoencephalopathy syndrome are distinct clinicoradiological disorders which
      share certain features in terms of aetiology, pathogenesis and symptomatology. We
      present a case of a young primigravida with eclampsia who developed severe
      headache, vision loss and hemiparesis in the postpartum phase. MRI of the brain
      was suggestive of the involvement of anterior as well as posterior circulation
      and reversibility of widespread angiographic constrictions could be documented on
      follow-up. Despite the resolution of vascular changes, vision loss did not
      improve significantly in our case. Such an overlap of findings is unusual and
      probably represents the spectrum of cerebral-autoregulatory dysfunction occurring
      in these two syndromes. 

PMID- 24311424
TI  - Dural sinus filling defect: intrasigmoid encephalocele.
AB  - Filling defects of dural venous sinuses are considered to be a challenging
      problem especially in case of symptomatic patients. Many lesions have to be ruled
      out such as sinus thrombosis, arachnoid granulations and tumours. Encephalocele
      into dural sinus is also a rare cause of these filling defects of dural sinuses.
      Here, we report an extremely rare case with spontaneous occult invagination of
      temporal brain tissue into the left sigmoid sinus and accompanying cerebellar
      ectopia. 

PMID- 24311425
TI  - Successful pregnancy in a woman with arthrogryposis multiplex congenita.
AB  - Arthrogryposis multiplex congenita refers to a clinical condition or syndrome
      characterised by multiple congenital contractures that affect two or more
      different areas of the body. Of the cases reported so far, an important
      percentage had to be terminated before pregnancy term, predominantly by caesarean
      section. We describe a 36 year-old woman who wanted to conceive. A
      multidisciplinary approach was set from the preconceptional period and special
      attention was given to respiratory function, potential anaesthetic difficulties
      and thromboembolic risks. She delivered by caesarean section at 38 weeks. This
      case emphasises the possibility of achieving a term delivery in these patients
      and points out the importance of a multidisciplinary team, specially of
      obstetricians and anaesthesiologists. 

PMID- 24311426
TI  - The life-saving little tip: intraosseous gas.
AB  - A case is presented of an-aerobic osteomyelitis with intraosseous gas resulting
      in the extension of gas in soft tissue structures in a patient with diabetes
      mellitus. The finding of intraosseous gas and its extension into the pubic joint
      and the left anterior abdominal wall is depicted. Intraosseous gas is a rare but
      worrying finding for osteomyelitis in the absence of a penetrative wound, recent
      surgery, biopsy or fracture. 

PMID- 24311427
TI  - PCP: thinking beyond HIV.
AB  - A 40-year-old man with a previous AIDS-defining opportunistic infection and five
      negative HIV tests presented to our outpatient clinic. The laboratory test was
      relevant for less than 300 total lymphocytes on two separate occasions. He was
      diagnosed with idiopathic CD4 lymphocytopenia and was started on antibiotic
      prophylaxis for Pneumocystis carinii pneumonia and Micobacterium avium
      intracellulare infection (MAI). This case report summarises the importance of
      further immunological characterisation in patients presenting with opportunistic
      infections and decreased cellular immunity. 

PMID- 24311428
TI  - Spontaneous pneumothorax as manifestation of Marfan syndrome.
AB  - The authors describe a 16-year-old boy, previously healthy, who was admitted to
      our hospital for left-sided spontaneous pneumothorax. On physical examination he
      presented with marfanoid habitus. Pneumothorax was managed conservatively with
      resolution. Four months later he had a recurrence of left-sided pneumothorax and
      1 week after that he presented with contralateral pneumothorax. He underwent
      video-assisted thoracoscopic surgery twice for bullectomy and pleurodesis. No
      further recurrence was stated. Additional investigation showed a prolapsed
      cardiac mitral valve and Marfan syndrome was confirmed genetically. 

PMID- 24311429
TI  - Multifocal osteoid osteoma of tibia.
AB  - Multifocal osteoid osteoma of the bone is extremely rare. We report a 25-year-old
      man who presented with pain in the left leg since 11 months which was partially
      relieved by over-the-counter analgesics. Radiograph demonstrated two lytic
      lesions with surrounding sclerosis along the anterior cortex of the left tibia.
      Three-phase Tc 99m bone and CT scans confirmed the diagnosis of multifocal
      osteoid osteoma. The patient underwent surgical excision followed by protected
      weight bearing. The patient was asymptomatic at 6 months postoperatively.
      Multifocal osteoid osteoma needs to be considered in the differential diagnosis
      of multiple lytic lesions in the bone. 

PMID- 24311430
TI  - Cerebellar hypoplasia in a case with neurofibromatosis type 1.

PMID- 24311431
TI  - The mystery of a carpenter's headache.

PMID- 24311432
TI  - Activated microglia in a rat stroke model express NG2 proteoglycan in peri
      infarct tissue through the involvement of TGF-beta1.
AB  - We investigated activated microglia in ischemic brain lesions from rats that had
      been subjected to transient middle cerebral artery occlusion. Activated microglia
      expressing NG2 chondroitin sulfate proteoglycan (NG2) were found only in the
      narrow zone (demarcation zone) that demarcated the peri-infarct tissue and
      ischemic core. NG2(-) activated microglia were abundantly distributed in the peri
      infarct tissue outside the demarcation zone. NG2(+) microglia but not NG2(-)
      microglia expressed both CD68 and a triggering receptor expressed on myeloid
      cells 2 (TREM-2), suggesting that NG2(+) microglia eliminated apoptotic neurons.
      In fact, NG2(+) microglia often attached to degenerating neurons and sometimes
      internalized NeuN(+) or neurofilament protein(+) material. Kinetic studies using
      quantitative real-time RT-PCR revealed that expression of transforming growth
      factor-beta1 (TGF-beta1) was most evident in the ischemic core; with this marker
      produced mainly by macrophages located in this region. TGF-beta receptor mRNA
      expression peaked at 3 days post reperfusion (dpr) in the peri-infarct tissue,
      including the demarcation zone. Primary cultured rat microglia also expressed the
      receptor mRNA. In response to TGF-beta1, primary microglia enhanced the
      expression of NG2 protein and TREM-2 mRNA as well as migratory activity. A TGF
      beta1 inhibitor, SB525334, abolished these effects. The present results suggest
      that TGF-beta1 produced in the ischemic core diffused toward the peri-infarct
      tissue, driving activated microglial cells to eliminate degenerating neurons.
      Appropriate control of NG2(+) microglia in the demarcation zone might be a novel
      target for the suppression of secondary neurodegeneration in the peri-infarct
      tissue.

PMID- 24311433
TI  - Small mosaic deletion encompassing the snoRNAs and SNURF-SNRPN results in an
      atypical Prader-Willi syndrome phenotype.
AB  - Genetic analyses were performed in a male patient with suspected Prader-Willi
      syndrome who presented with hypogonadism, excessive eating, central obesity,
      small hands and feet and cognition within the low normal range. However, he had
      no neonatal hypotonia or feeding problems during infancy. Chromosome analysis
      showed a normal male karyotype. Further analysis with array-CGH identified a
      mosaic 847 kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene
      clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and
      B), SNORD64 (HBII-13), and NPAP1 (C15ORF2). MLPA confirmed the deletion and the
      results were compatible with a paternal origin. Metaphase-FISH verified the
      mosaicism with the deletion present in 58% of leukocytes analyzed. Three smaller
      deletions in this region have previously been reported in patients with Prader
      Willi syndrome phenotype. All three deletions included SNORD116, but only two
      encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor
      to the Prader-Willi phenotype. Our case adds further information about genotype
      phenotype correlation and supports the hypothesis that SNORD116 plays a major
      role in the pathogenesis of Prader-Willi syndrome. Furthermore, it examplifies
      diagnostic difficulties in atypical cases and illustrates the need for additional
      testing methods when Prader-Willi syndrome is suspected.

PMID- 24311434
TI  - A uranium-based UO2(+)-Mn2+ single-chain magnet assembled trough cation-cation
      interactions.
AB  - Single-chain magnets (SCMs) are materials composed of magnetically isolated one
      dimensional (1D) units exhibiting slow relaxation of magnetization. The
      occurrence of SCM behavior requires the fulfillment of stringent conditions for
      exchange and anisotropy interactions. Herein, we report the synthesis, the
      structure, and the magnetic characterization of the first actinide-containing
      SCM. The 5f-3d heterometallic 1D chains [{[UO2(salen)(py)][M(py)4](NO3)}]n, (M=Cd
      (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction
      from the reaction of the uranyl(V) complex [UO2(salen)py][Cp*2Co]
      (Cp*=pentamethylcyclopentadienyl) with Cd(NO3)2 or Mn(NO3)2 in pyridine. The
      infinite UMn chain displays a high relaxation barrier of 134+/-0.8 K (93+/-0.5
      cm(-1)), probably as a result of strong intra-chain magnetic interactions
      combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also
      exhibits an open magnetic hysteresis loop at T<6 K, with an impressive coercive
      field of 3.4 T at 2 K.

PMID- 24311435
TI  - When will collective action be effective? Violent and non-violent protests
      differentially influence perceptions of legitimacy and efficacy among
      sympathizers.
AB  - Collective action will be effective in achieving broader social change goals to
      the extent that it influences public opinion yet the degree to which collective
      action "works" in changing opinion is rarely studied. Experiment 1 (n = 158)
      showed that, consistent with a logic of strategic non-violence, non-violent
      collective action more effectively conveys a sense of the illegitimacy of the
      issue and the efficacy of the group, thereby promoting support for future non
      violent actions. Experiment 2 (n = 139) explored the moderating role of
      allegations of corruption. A social context of corruption effectively undermined
      the efficacy and legitimacy of non-violent collective action, relative to support
      for violence, thereby promoting (indirectly) support for future extreme action.
      The implications of this research, for the logic of strategic non-violence and
      mobilizing supportive public opinion, are discussed. 

PMID- 24311436
TI  - Effects of self-relevant perspective-taking on the impact of persuasive appeals.
AB  - Donation appeals often describe the situations that confront victims of
      misfortune and advertisements for consumer products often show people using the
      products being promoted. When people consider these messages from the perspective
      of the individuals described in them, they often imagine the reactions they would
      have if they personally experienced the situation described. When this occurs,
      they are likely to be influenced by the messages independently of the
      protagonists' characteristics. When recipients' attention is drawn to themselves,
      however, they compare themselves with the protagonists to determine whether the
      protagonists' actions or the situation described in the message have implications
      for their own behavior. This self-focused attention increases the impact of the
      message when they are similar to the protagonists, decreases its impact when they
      are moderately dissimilar, and has no effect at all when they are very dissimilar
      to the protagonists. Two experiments, in which participants' self-focused
      attention, the type of persuasive appeal (self-referential vs. impersonal), and
      protagonist-participant similarity were independently manipulated, confirmed
      these effects on the impact of both (a) an appeal for monetary donations to a
      charity and (b) a commercial advertisement. 

PMID- 24311437
TI  - Cultural prototypes and dimensions of honor.
AB  - Research evidence and theoretical accounts of honor point to differing
      definitions of the construct in differing cultural contexts. The current studies
      address the question "What is honor?" using a prototype approach in Turkey and
      the Northern United States. Studies 1a/1b revealed substantial differences in the
      specific features generated by members of the two groups, but Studies 2 and 3
      revealed cultural similarities in the underlying dimensions of self-respect,
      moral behavior, and social status/respect. Ratings of the centrality and personal
      importance of these factors were similar across the two groups, but their
      association with other relevant constructs differed. The tripartite nature of
      honor uncovered in these studies helps observers and researchers alike understand
      how diverse responses to situations can be attributed to honor. Inclusion of a
      prototype analysis into the literature on honor cultures can provide enhanced
      coverage of the concept that may lead to testable hypotheses and new theoretical
      developments. 

PMID- 24311438
TI  - Simulation of drug distribution in the vitreous body after local drug application
      into intact vitreous body and in progress of posterior vitreous detachment.
AB  - Intravitreal injections and drug-loaded implants are current approaches to treat
      diseases of the posterior eye. To investigate the release of active agents and
      their distribution in the vitreous body, a new test system was developed that
      enables a realistic simulation of eye motions. It is called the eye movement
      system (EyeMoS). In combination with a previously developed model containing a
      polyacrylamide gel as a substitute for the vitreous body, this new system enables
      the characterization of the influence of eye motions on drug distribution within
      the vitreous body. In the presented work, the distribution of fluorescence-tagged
      model drugs of different molecular weight within the simulated vitreous was
      examined under movement with the EyeMoS and without movement. By replacing a part
      of the gel in the simulated vitreous body with buffer, the influence of the
      progress of posterior vitreous detachment (PVD) on the distribution of these
      model substances was also studied. The results indicate that convective forces
      may be of predominate influence on initial drug distribution. The impact of these
      forces on drug transport increases with simulated progression of PVD. Using the
      EyeMoS, the investigation of release and distribution from intravitreal drug
      delivery systems becomes feasible under biorelevant conditions.

PMID- 24311439
TI  - Genetic drift. Lucky.

PMID- 24311440
TI  - Hepatic interferon-stimulated genes are differentially regulated in the liver of
      chronic hepatitis C patients with different interleukin-28B genotypes.
AB  - Pretreatment up-regulation of hepatic interferon (IFN)-stimulated genes (ISGs)
      has a stronger association with the treatment-resistant interleukin (IL)28B minor
      genotype (MI; TG/GG at rs8099917) than with the treatment-sensitive IL28B major
      genotype (MA; TT at rs8099917). We compared the expression of ISGs in the liver
      and blood of 146 patients with chronic hepatitis C who received pegylated IFN and
      ribavirin combination therapy. Gene expression profiles in the liver and blood of
      85 patients were analyzed using an Affymetrix GeneChip (Affymetrix, Santa Clara,
      CA). ISG expression was correlated between the liver and blood of the MA
      patients, whereas no correlation was observed in the MI patients. This loss of
      correlation was the result of the impaired infiltration of immune cells into the
      liver lobules of MI patients, as demonstrated by regional gene expression
      analysis in liver lobules and portal areas using laser capture microdissection
      and immunohistochemical staining. Despite having lower levels of immune cells,
      hepatic ISGs were up-regulated in the liver of MI patients and they were found to
      be regulated by multiple factors, namely, IL28A/B, IFN-lambda4, and wingless
      related MMTV integration site 5A (WNT5A). Interestingly, WNT5A induced the
      expression of ISGs, but also increased hepatitis C virus replication by inducing
      the expression of the stress granule protein, GTPase-activating protein (SH3
      domain)-binding protein 1 (G3BP1), in the Huh-7 cell line. In the liver, the
      expression of WNT5A and its receptor, frizzled family receptor 5, was
      significantly correlated with G3BP1. CONCLUSIONS: Immune cells were lost and
      induced the expression of other inflammatory mediators, such as WNT5A, in the
      liver of IL28B minor genotype patients. This might be related to the high level
      of hepatic ISG expression in these patients and the treatment-resistant phenotype
      of the IL28B minor genotype.

PMID- 24311441
TI  - Nutritional factors and aging in demyelinating diseases.
AB  - Demyelination is a pathological process characterized by the loss of myelin
      around axons. In the central nervous system, oligodendroglial damage and
      demyelination are common pathological features characterizing white matter and
      neurodegenerative disorders. Remyelination is a regenerative process by which
      myelin sheaths are restored to demyelinated axons, resolving functional deficits.
      This process is often deficient in demyelinating diseases such as multiple
      sclerosis (MS), and the reasons for the failure of repair mechanisms remain
      unclear. The characterization of these mechanisms and the factors involved in the
      proliferation, recruitment, and differentiation of oligodendroglial progenitor
      cells is key in designing strategies to improve remyelination in demyelinating
      disorders. First, a very dynamic combination of different molecules such as
      growth factors, cytokines, chemokines, and different signaling pathways is
      tightly regulated during the remyelination process. Second, factors unrelated to
      this pathology, i.e., age and genetic background, may impact disease progression
      either positively or negatively, and in particular, age-related remyelination
      failure has been proven to involve oligodendroglial cells aging and their
      intrinsic capacities among other factors. Third, nutrients may either help or
      hinder disease progression. Experimental evidence supports the anti-inflammatory
      role of omega-6 and omega-3 polyunsaturated fatty acids through the competitive
      inhibition of arachidonic acid, whose metabolites participate in inflammation,
      and the reduction in T cell proliferation. In turn, vitamin D intake and
      synthesis have been associated with lower MS incidence levels, while vitamin D
      gene interactions might be involved in the pathogenesis of MS. Finally, dietary
      polyphenols have been reported to mitigate demyelination by modulating the immune
      response. 

PMID- 24311442
TI  - Identifying evolutionarily conserved genes in the dietary restriction response
      using bioinformatics and subsequent testing in Caenorhabditis elegans.
AB  - Dietary restriction (DR) increases life span, health span and resistance to
      stress in a wide range of organisms. Work from a large number of laboratories has
      revealed evolutionarily conserved mechanisms that mediate the DR response. Here,
      we analyzed the genome-wide gene expression profiles of Caenorhabditis elegans
      under DR versus ad libitum conditions. Using the Ortho2ExpressMatrix tool, we
      searched for C. elegans orthologs of mouse genes that have been shown to be
      differentially expressed under DR conditions in nearly 600 experiments. Based on
      our bioinformatic approaches, we obtained 189 DR-responsive genes, and 45 of
      these are highly conserved from worm to man. Subsequent testing of sixteen genes
      that are up-regulated under DR identified eight genes that abolish the DR-induced
      resistance to heat stress in C. elegans. Further analyses revealed that fkb-4,
      dod-22 and ikb-1 genes also abolish increased life span in response to DR. The
      identified genes that are necessary for the DR response are sensitive to certain
      stress signals such as metabolic perturbances (dod-22, fkb-4 and nhr-85), DNA
      damage (ikb-1), heat shock (hsp-12.6) and cancer-like overgrowth (prk-2 and tsp
      15). We propose that most of the DR-responsive genes identified are components of
      the recently discovered cellular surveillance-activated detoxification and
      defenses pathway, which is, among others, important for the survival of organisms
      in times of food deprivation. 

PMID- 24311443
TI  - Estrogen or raloxifene during postmenopausal weight loss: adiposity and
      cardiometabolic outcomes.
AB  - OBJECTIVE: Estrogen-based hormone therapy (HT) attenuates abdominal fat gain
      after menopause, but whether HT improves abdominal fat loss during weight loss is
      unknown. It was hypothesized that HT or a selective estrogen receptor modulator
      (raloxifene) would augment reductions in abdominal visceral fat during weight
      loss when compared to placebo, potentially increasing improvements in glucose
      tolerance and lipid profile. METHODS: Healthy postmenopausal women (n = 119; age
      50-70 yr) underwent a 6-month weight-loss (primarily exercise) intervention with
      randomization to raloxifene (60 mg/d), HT (conjugated estrogens, 0.625 mg/d), or
      placebo. Outcomes were change in total and abdominal (visceral and subcutaneous)
      fat mass, lipid profile, and fasting and post-challenge glucose and insulin.
      RESULTS: Neither HT nor raloxifene augmented loss of total or abdominal fat mass
      during exercise-induced weight loss when compared with placebo. Weight loss
      induced improvements in risk factors were similar among the three groups, except
      for a greater reduction in fasted glucose in the HT group (difference in change
      [95%CI] from placebo; -0.40 [-0.76, -0.05]) and greater reductions in LDL (-0.36
      [-0.63, -0.09]) and increases in HDL (0.15 [0.07, 0.24]) in both treatment
      groups. CONCLUSIONS: Postmenopausal HT and raloxifene did not increase abdominal
      fat loss during weight loss, but did improve some cardiometabolic outcomes.

PMID- 24311445
TI  - Developing criminal justice liaison and diversion services: research priorities
      and international learning.

PMID- 24311444
TI  - Initial design of culturally informed behavioral intervention technologies:
      developing an mHealth intervention for young sexual minority men with generalized
      anxiety disorder and major depression.
AB  - BACKGROUND: To our knowledge, there is no well-articulated process for the design
      of culturally informed behavioral intervention technologies. OBJECTIVE: This
      paper describes the early stages of such a process, illustrated by the
      methodology for the ongoing development of a behavioral intervention technology
      targeting generalized anxiety disorder and major depression among young sexual
      minority men. METHODS: We integrated instructional design for Internet behavioral
      intervention technologies with greater detail on information sources that can
      identify user needs in understudied populations, as well as advances in the
      understanding of technology-specific behavioral intervention technology
      dimensions that may need to be culturally tailored. RESULTS: General
      psychological theory describing how to effect change in the clinical target is
      first integrated with theory describing potentially malleable factors that help
      explain the clinical problem within the population. Additional information
      sources are then used to (1) evaluate the theory, (2) identify population
      specific factors that may affect users' ability to relate to and benefit from the
      behavioral intervention technology, and (3) establish specific skills, attitudes,
      knowledge, etc, required to change malleable factors posited in the theory. User
      needs result from synthesis of this information. Product requirements are then
      generated through application of the user needs to specific behavioral
      intervention technology dimensions (eg, technology platform). We provide examples
      of considerations relevant to each stage of this process and how they were
      applied. CONCLUSIONS: This process can guide the initial design of other
      culturally informed behavioral intervention technologies. This first attempt to
      create a systematic design process can spur development of guidelines for design
      of behavioral intervention technologies aimed to reduce health disparities.

PMID- 24311446
TI  - A3 Adenosine receptors mediate oligodendrocyte death and ischemic damage to optic
      nerve.
AB  - Adenosine receptor activation is involved in myelination and in apoptotic
      pathways linked to neurodegenerative diseases. In this study, we investigated the
      effects of adenosine receptor activation in the viability of oligodendrocytes of
      the rat optic nerve. Selective activation of A3 receptors in pure cultures of
      oligodendrocytes caused concentration-dependent apoptotic and necrotic death
      which was preceded by oxidative stress and mitochondrial membrane depolarization.
      Oligodendrocyte apoptosis induced by A3 receptor activation was caspase-dependent
      and caspase-independent. In addition to dissociated cultures, incubation of optic
      nerves ex vivo with adenosine and the A3 receptor agonist 2-CI-IB-MECA(1-[2
      Chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D
      ribofuranuronamide)-induced caspase-3 activation, oligodendrocyte damage, and
      myelin loss, effects which were prevented by the presence of caffeine and the A3
      receptor antagonist MRS 1220 (N-[9-Chloro-2-(2-furanyl)[1,2,4]-triazolo [1,5
      c]quinazolin-5-yl]benzene acetamide). Finally, ischemia-induced injury and
      functional loss to the optic nerve was attenuated by blocking A3 receptors.
      Together, these results indicate that adenosine may trigger oligodendrocyte death
      via activation of A3 receptors and suggest that this mechanism contributes to
      optic nerve and white matter ischemic damage.

PMID- 24311447
TI  - Primary care physician communication at hospital discharge reduces medication
      discrepancies.
AB  - BACKGROUND: Medication discrepancies are common as patients transition from
      hospital to home. Errors with post-discharge medication regimens may play a role
      in hospital readmissions. OBJECTIVES: To determine whether primary care physician
      (PCP) contact with patients at hospital discharge impacts the frequency of
      medication discrepancies at 24 hours post-discharge. DESIGN: With the PCP
      Enhanced Discharge Communication Intervention, PCPs were asked to speak with
      treating hospitalists and contact patients within 24 hours of hospital discharge
      (either in person or by phone) to discuss any hospital medication changes.
      Research staff enrolled subjects during their hospitalization and telephoned
      subjects 48 hours post-discharge to determine medication discrepancies and PCP
      contact. PARTICIPANTS: One hundred fourteen community-dwelling adults, admitted
      to acute medicine services >24 hours on >= 5 medications. RESULTS: Of the 114
      subjects enrolled in the hospital, 75 subjects completed 48 hours postdischarge
      phone interviews. Of the 75 study patients, 39 patients (50.6%) experienced a
      total of 84 medication discrepancies (mean, 2.1 discrepancies/patient). Subjects
      who were contacted by their PCP at discharge were 70% less likely to have a
      discrepancy when compared with those not contacted (P = 0.04). Males were 4.34
      times more likely to have a discrepancy (P = 0.02). CONCLUSION: PCP communication
      with patients within 24 hours of discharge was associated with decreased
      medication discrepancies. Our results further demonstrate the importance of PCP
      involvement in the hospital discharge process.

PMID- 24311448
TI  - Studying documentation.

PMID- 24311449
TI  - Mild bioconjugation through the oxidative coupling of ortho-aminophenols and
      anilines with ferricyanide.
AB  - Using a small-molecule-based screen, ferricyanide was identified as a mild and
      efficient oxidant for the coupling of anilines and o-aminophenols on protein
      substrates. This reaction is compatible with thiols and 1,2-diols, allowing its
      use in the creation of complex bioconjugates for use in biotechnology and
      materials applications. 

PMID- 24311450
TI  - Inherited dup(17)(p11.2p11.2): expanding the phenotype of the Potocki-Lupski
      syndrome.
AB  - Potocki-Lupski syndrome (PTLS, OMIM: 610883) is a microduplication syndrome
      characterized by infantile hypotonia, failure to thrive, cardiovascular
      malformations, developmental delay, intellectual disability, and behavior
      abnormalities, the latter of which can include autism spectrum disorder. The
      majority of individuals with PTLS harbor a de novo microduplication of chromosome
      17p11.2 reciprocal to the common recurrent 3.6 Mb microdeletion in the Smith
      Magenis syndrome critical region. Here, we report on the transmission of the PTLS
      duplication across two generations in two separate families. Individuals in these
      families presented initially with developmental delay, behavior problems, and
      intellectual disability. We provide a detailed review of the clinical and
      developmental phenotype of inherited PTLS in both families. This represents the
      second report (second and third families) of PTLS in a parent-child pair and
      exemplifies the under-diagnosis of this and likely other genetic conditions in
      adults with intellectual disability and/or psychiatric disorders.

PMID- 24311451
TI  - Big breakfast rich in protein and fat improves glycemic control in type 2
      diabetics.
AB  - OBJECTIVE: Our goal was to evaluate the effect of breakfast size and composition
      on body weight, glycemic control, and metabolic markers in adults with type 2
      diabetes mellitus (T2DM). METHODS: 59 overweight/obese adults with T2DM were
      randomized to one of two isocaloric diabetic diets for 3 months; big breakfast
      (BB), breakfast was rich in fat and protein and provided 33% of total daily
      energy or small breakfast (SB), breakfast was rich in carbohydrates and provided
      12.5% of total daily energy. RESULTS: Although body weight was reduced similarly
      in both groups, the BB group showed greater HbA1c and systolic blood pressure
      reductions (HbA1c: -4.62% vs. -1.46%, p = 0.047; SBP -9.58 vs. -2.43 mmHg; p =
      0.04). T2DM medication dose was reduced in a greater proportion of the BB
      participants (31% vs. 0%; p = 0.002) while in the SB, a greater proportion of
      participants had a dose increases (16.7% vs. 3.4%; p = 0.002). Hunger scores were
      lower in the BB group and greater improvements in fasting glucose were observed
      in the BB group. CONCLUSIONS: A simple dietary manipulation enriching breakfast
      with energy as protein and fat appears to confer metabolic benefits and might be
      a useful alternative for the management of T2DM.

PMID- 24311452
TI  - A patient with a duplication of chromosome 3p (p24.1p26.2): a comparison with
      other partial 3p trisomies.

PMID- 24311453
TI  - Rho kinase inhibition modulates microglia activation and improves survival in a
      model of amyotrophic lateral sclerosis.
AB  - Disease progression in amyotrophic lateral sclerosis (ALS) is characterized by
      degeneration of motoneurons (MN) and their axons, but is also influenced by
      neighboring cells such as astrocytes and microglial cells. The role of microglia
      in ALS is complex as it switches from an anti-inflammatory and neuroprotective
      phenotype in early disease to a proinflammatory and neurotoxic phenotype in later
      stages. Our previous studies in models of neurodegeneration identified rho kinase
      (ROCK) as a target, which can be manipulated to beneficially influence disease
      progression. Here, we examined the neuroprotective potential of the ROCK
      inhibitor Fasudil to target the central pathogenic features of ALS. Application
      of Fasudil to kainic acid-lesioned primary MN in vitro resulted in a strong
      prosurvival effect. In vivo, SOD1(G93A) mice benefited from oral treatment with
      Fasudil showing prolonged survival and improved motor function. These findings
      were correlated to an improved survival of motor neurons and a pronounced
      alteration of astroglial and microglial cell infiltration of the spinal cord
      under Fasudil treatment. Modeling a proinflammatory microglial phenotype by
      stimulation with LPS in vitro, Fasudil decreased the release of proinflammatory
      cytokines and chemokines TNFalpha, Il6, CCL2, CCL3, and CCL5 while CXCL1 release
      was only transiently suppressed. In sciatic nerve motor axons, neuromuscular
      junction remodeling processes were increased. In conclusion, we provide
      preclinical and neurobiological evidence that inhibition of ROCK by the
      clinically approved small molecule inhibitor Fasudil may be a novel therapeutic
      approach in ALS combining both neuroprotection and immunomodulation for the cure
      of this devastating disease.

PMID- 24311454
TI  - Involvement of PtdIns(4,5)P2 in the regulatory mechanism of small intestinal P
      glycoprotein expression.
AB  - Previously, we reported that repeated oral administration of etoposide (ETP)
      activates the ezrin/radixin/moesin (ERM) scaffold proteins for P-glycoprotein (P
      gp) via Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil
      containing protein kinase (ROCK) signaling, leading to increased ileal P-gp
      expression. Recent studies indicate that phosphatidyl inositol 4,5-bisphosphate
      [PtdIns(4,5)P2] regulates the plasma-membrane localization of certain proteins,
      and its synthase, the type I phosphatidyl inositol 4-phosphate 5-kinase (PI4P5K),
      is largely controlled by RhoA/ROCK. Here, we examined whether PtdIns(4,5)P2 and
      PI4P5K are involved in the increased expression of ileal P-gp following the ERM
      activation by ETP treatment. Male ddY mice (4-week-old) were treated with ETP (10
      mg/kg/day, per os, p.o.) for 5 days. Protein-expression levels were measured by
      either western blot or dot blot analysis and molecular interactions were assessed
      using immunoprecipitation assays. ETP treatment significantly increased PI4P5K,
      ERM, and P-gp expression in the ileal membrane. This effect was suppressed
      following the coadministration of ETP with rosuvastatin (a RhoA inhibitor) or
      fasudil (a ROCK inhibitor). Notably, the PtdIns(4,5)P2 expression in the ileal
      membrane, as well as both P-gp and ERM levels coimmunoprecipitated with anti
      PtdIns(4,5)P2 antibody, were increased by ETP treatment. PtdIns(4,5)P2 and PI4P5K
      may contribute to the increase in ileal P-gp expression observed following the
      ETP treatment, possibly through ERM activation via the RhoA/ROCK pathway.

PMID- 24311455
TI  - Prevalence and characteristics of hospitalized adults on chronic opioid therapy.
AB  - BACKGROUND: As chronic opioid therapy (COT) becomes more common, complexity of
      pain management in the inpatient setting increases; little is known about medical
      inpatients on COT. OBJECTIVE: To determine the prevalence of COT among
      hospitalized patients and to compare outcomes among these patients relative to
      those not receiving COT. DESIGN: Observational study of inpatient and outpatient
      administrative data. PARTICIPANTS: All veterans with acute medical admissions to
      129 Veterans Administration hospitals during fiscal years 2009 to 2011, residing
      in the community, and with outpatient pharmacy use. MEASUREMENTS: We defined COT
      as 90 or more days of opioids prescribed in the 6 months prior to
      hospitalization. Patient characteristics included demographic variables and major
      comorbidities. Outcomes included 30-day readmission and death during
      hospitalization or within 30 days, with associations ascertained using
      multivariable logistic regression. RESULTS: Of 122,794 hospitalized veterans,
      31,802 (25.9%) received COT. These patients differed from comparators in age,
      sex, race, residence, and presence of chronic noncancer pain, chronic obstructive
      pulmonary disease, complicated diabetes, cancer, and mental health diagnoses
      including post-traumatic stress disorder. After adjustment for demographic
      factors, comorbidities, and admission diagnosis, COT was associated with hospital
      readmission (odds ratio [OR]: 1.15, 95% confidence interval [CI]: 1.10-1.20) and
      death (OR: 1.19, 95% CI: 1.10-1.29). CONCLUSIONS: COT is common among medical
      inpatients. Patients on COT differ from patients without COT beyond
      dissimilarities in pain and cancer diagnoses. Occasional and chronic opioid use
      are associated with increased risk of hospital readmission, and COT is associated
      with increased risk of death. Additional research relating COT to hospitalization
      outcomes is warranted.

PMID- 24311456
TI  - Homometallic rare-Earth metal phosphinidene clusters: synthesis and reactivity.
AB  - Two new trinuclear MU3 -bridged rare-earth metal phosphinidene complexes,
      [{L(Ln)(MU-Me)}3 (MU3 -Me)(MU3 -PPh)] (L=[PhC(NC6 H4 iPr2 -2,6)2 ](-) , Ln=Y (2
      a), Lu (2 b)), were synthesized through methane elimination of the corresponding
      carbene precursors with phenylphosphine. Heating a toluene solution of 2 at 120 
      degrees C leads to an unprecedented ortho C?H bond activation of the PhP ligand
      to form the bridged phosphinidene/phenyl complexes. Reactions of 2 with ketones,
      thione, or isothiocyanate show clear phospha-Wittig chemistry, giving the
      corresponding organic phosphinidenation products and oxide (sulfide) complexes.
      Reaction of 2 with CS2 leads to the formation of novel trinuclear rare-earth
      metal thione dianion clusters, for which a possible pathway was determined by DFT
      calculation. 

PMID- 24311457
TI  - Multiple cafe au lait spots in familial patients with MAP2K2 mutation.
AB  - Recent advances in genetic diagnostic technologies have made the classic disease
      nosology highly complicated. This situation is exemplified by rasopathies, among
      which neurofibromatosis type 1 and Noonan syndrome represent prototypic entities.
      The former condition is characterized by multiple cafe au lait spots and
      neurofibromas, while the latter is characterized by distinct facial features,
      webbed neck, congenital heart disease, and a short stature. On rare occasions,
      the features of both neurofibromatosis and Noonan syndrome co-exist within an
      individual; such patients are diagnosed as having neurofibromatosis-Noonan
      syndrome. Here, we report familial patients with multiple cafe au lait spots and
      Noonan syndrome-like facial features. A mutation analysis unexpectedly revealed a
      mutation in MAP2K2 in both the propositus and his mother. The propositus
      fulfilled the diagnostic criteria for neurofibromatosis type 1, but his mother
      did not. Their phenotype was not consistent with that of cardio-facio-cutaneous
      syndrome, which is classically known to be associated with MAP2K2 mutations. The
      mother of the propositus had cervical cancer at the age of 23 years, consistent
      with the oncogenic tendency associated with rasopathies. The phenotypic
      combination of multiple cafe au lait spots and Noonan syndrome-like facial
      features suggested a diagnosis of neurofibromatosis-Noonan syndrome. Whether this
      condition represents a discrete disease entity or a variable expression of
      neurofibromatosis type 1 has long been debated. The present observation suggests
      that some perturbation in the RAS/MAPK signaling cascade results in multiple cafe
      au lait spots, a key diagnostic phenotype of rasopathies, although the exact
      mechanism remains to be elucidated.

PMID- 24311458
TI  - Porous diaphragm syndrome: haemothorax secondary to haemoperitoneum following
      laparoscopic hysterectomy.
AB  - The porous diaphragm syndrome is associated with the presence of diaphragmatic
      fenestrations creating peritoneopleural communications. Such defects may occur in
      conditions associated with a rise on intra-abdominal pressure including
      laparoscopic surgery. Thoracic complications of laparoscopic surgery may occur as
      a result. A 48-year-old woman underwent a total laparoscopic hysterectomy for
      heavy menstrual bleeding. The postoperative period was complicated by
      haemoperitoneum resulting in haemothorax secondary to porous diaphragm syndrome.
      Surgeons and anaesthetists should be aware of the possibility of serious thoracic
      complications related to laparoscopic surgery. 

PMID- 24311459
TI  - Post-traumatic tics and tetrabenazine treatment: a blinded video assessment.
AB  - Traumatic head injury is a very rare cause of secondary tic disorders. We add
      another case by describing, for the first time, the response to tetrabenazine in
      a blinded video assessment. Our patient had a severe traumatic head injury and
      subsequently developed tics refractory to various agents including neuroleptics.
      We assessed tetrabenazine treatment by virtue of patient's impression, the
      treating neurologist's non-blinded (Yale Global Tic Severity Scale) and a second
      neurologist's blinded assessment (modified Rush Video Scale). The Yale Global Tic
      Severity Score improved by 24% on 12.5 mg twice daily and 45% on 12.5 mg thrice
      daily. Subjective improvement was 50% and 70%, respectively. The modified Rush
      Video scores improved by 21% and 28.5%, respectively. Post-traumatic tourettism
      can respond to tetrabenazine. The magnitude of benefit though, may be
      overestimated with open-label observations, thus there is a need for studies
      examining objectively the effect of tetrabenazine in tic disorders. 

PMID- 24311460
TI  - Porcelain aorta with critical left main disease and severe aortic stenosis in a
      patient with heterozygous familial hyperlipidaemia presenting with cardiogenic
      shock.

PMID- 24311461
TI  - A population-level analysis of 5620 recipients of multiple in-hospital
      cardiopulmonary resuscitation attempts.
AB  - BACKGROUND: There is a paucity of data examining the epidemiology of recipients
      of multiple in-hospital cardiopulmonary resuscitation (CPR) attempts, and their
      outcomes. METHODS:  DATA SOURCE: Nationwide Inpatient Sample, 2000 to 2009.
      Patient characteristics, survival to discharge, discharge disposition, and cost
      of hospitalization of patients who had 1 versus multiple (>1) CPR attempts were
      compared using bivariate and multivariate methods. RESULTS: Of 166,519
      hospitalized CPR recipients, 3.4% had multiple CPR attempts. Compared with 1-time
      CPR recipients, those undergoing multiple CPR were younger (age <65 years; 37.3%
      vs 42.5%, respectively), more often nonwhite (34.2% vs 41.4%), and commonly
      treated in nonteaching hospitals (58.0% vs 64.5%; all P < 0.001). Survival to
      discharge decreased by >40% for each additional CPR attempt (23.4% vs 11.9%, and
      6.7% for 1, 2, and >=3 CPR attempts, respectively; P < 0.001). After multivariate
      adjustment, multiple CPR was independently associated with a lower survival to
      discharge (odds ratio: 0.41, 95% confidence interval: 0.37-0.44, P < 0.001).
      Recipients of multiple CPR were more likely to be discharged to destinations
      other than home (80.7% vs 70.1%, P < 0.001); 1 in 15 survivors of multiple CPR
      were discharged to hospice (6.8%), compared with 1 in 23 patients (4.3%) who had
      1 CPR (P = 0.002). The average cost per day of hospitalization was higher for
      patients who had multiple CPR versus 1 CPR ($4484.60 vs $3581.40, P < 0.001).
      CONCLUSIONS: Recipients of multiple in-hospital CPR attempts are more likely to
      be younger, nonwhite, and treated in nonteaching hospitals. Survival to discharge
      is significantly worse, and the cost of hospitalization is considerably higher
      for these patients.

PMID- 24311462
TI  - Haploinsufficiency of BMP4 gene may be the underlying cause of Frias syndrome.
AB  - In 2005, we reported on a family as having Frias syndrome (OMIM: 609640), with
      four affected members displaying a pattern of congenital defects nearly identical
      to those observed in a mother and son described by Frias [Frias et al. (1975).
      Birth Defects Orig Artic Ser 11:30-33]. These defects included growth deficiency,
      facial anomalies, and hand and foot alterations. We had the opportunity to study
      this family again due to the birth of another affected girl, who presented with
      similar facial characteristics to those of her elder half-sister and the rest of
      affected relatives, which consisted of mild exophthalmia, bilateral palpebral
      ptosis, downslanting palpebral fissures, and hypertelorism. We performed array
      CGH, which identified an identical interstitial deletion of chromosome 14q22.1
      q22.3 in the mother and two daughters. The deletion is 4.06 Mb in length and
      includes the BMP4 gene, a member of the bone morphogenetic protein (BMP) family
      of secreted proteins. A review of the literature showed that deletions or
      mutations of this gene underlie congenital defects affecting brain, eye, teeth,
      and digit development. Although the clinical manifestations of the current family
      correlate with the defects observed in patients having either 14q22-q23 deletions
      or mutations of BMP4, they show a milder phenotype. In order to understand the
      clinical variability, we evaluated the already known functional characteristics
      of the BMP gene members. This gene family plays an important role during early
      embryogenesis, and the complex synergistic functions and redundancies of the BMPs
      led us to conclude that haploinsufficiency of BMP4 is likely to be responsible
      for the clinical expression of Frias syndrome.

PMID- 24311464
TI  - The colloidal stabilization of carbon with carbon: carbon nanobubbles as both
      dispersant and glue for carbon nanotubes.
AB  - The superior physical properties of carbon nanotubes (CNTs) have led to their
      broad application. Intrinsically, CNTs tend to agglomerate from hydrophobic
      interactions, which is highly undesirable for solution processing and device
      fabrication. Commonly, a stabilizer consisting of organic surfactants or polymers
      is used to disperse CNTs. Recently, we synthesized nitrogen-doped carbon hollow
      nanospheres (25-90 nm), termed carbon "nanobubbles". They bear superior
      dispersability in water and distinctive graphitic order. Herein, we describe the
      nanobubble-assisted dispersion of CNTs in aqueous solution upon sonication. This
      process relies on the pi-pi interaction between the two aromatic carbon
      nanostructures, which can process their carbon mixture in water into conductive
      filter membranes, ink, and discs. This stabilization can be extended to other
      aromatic carbons. In addition, the pi-pi interaction may create a new type of
      carbon p-n junction that can be used to improve charge separation. 

PMID- 24311463
TI  - Dissociation of innate immune responses in microglia infected with Listeria
      monocytogenes.
AB  - Microglia, the innate immune cells of the brain, plays a central role in cerebral
      listeriosis. Here, we present evidence that microglia control Listeria infection
      differently than macrophages. Infection of primary microglial cultures and murine
      cell lines with Listeria resulted in a dual function of the two gene expression
      programmes involved in early and late immune responses in macrophages. Whereas
      the bacterial gene hly seems responsible for both transcriptional programmes in
      macrophages, Listeria induces in microglia only the tumor necrosis factor (TNF)
      regulated transcriptional programme. Listeria also represses in microglia the
      late immune response gathered in two clusters, microbial degradation, and
      interferon (IFN)-inducible genes. The bacterial gene actA was required in
      microglia to induce TNF-regulated responses and to repress the late response.
      Isolation of microglial phagosomes revealed a phagosomal environment unable to
      destroy Listeria. Microglial phagosomes were also defective in several signaling
      and trafficking components reported as relevant for Listeria innate immune
      responses. This transcriptional strategy in microglia induced high levels of TNF
      alpha and monocyte chemotactic protein-1 and low production of other neurotoxic
      compounds such as nitric oxide, hydrogen peroxide, and Type I IFNs. These
      cytokines and toxic microglial products are also released by primary microglia,
      and this cytokine and chemokine cocktail display a low potential to trigger
      neuronal apoptosis. This overall bacterial strategy strongly suggests that
      microglia limit Listeria inflammation pattern exclusively through TNF-mediated
      responses to preserve brain integrity.

PMID- 24311465
TI  - The childless man.

PMID- 24311466
TI  - Pelvic floor trauma: does the second baby matter?
AB  - OBJECTIVE: To ascertain the effect of a second delivery on pelvic floor anatomy.
      METHODS: This was a retrospective analysis of data obtained in two perinatal
      imaging studies. Women were invited for antenatal and two postnatal appointments.
      All had answered a standardized questionnaire and undergone a clinical
      examination and translabial four-dimensional ultrasound. Ultrasound volumes were
      acquired at rest, on Valsalva maneuver and on pelvic floor muscle contraction,
      and analyzed by postprocessing on a PC. Avulsion was diagnosed on tomographic
      ultrasound imaging. This study reports data obtained in those women who delivered
      a second child between the first and second postnatal assessments. RESULTS: Of
      715 participants, 94 reported a second birth at their second postnatal
      appointment on average 2.7 years after their first birth; 65 had a vaginal
      delivery and 29 a Cesarean section. There were nine attempts at vaginal birth
      after Cesarean section (VBAC), of which six were successful. When we analyzed the
      ultrasound findings before and after a second delivery, there was no significant
      change observed in bladder-neck descent, cystocele descent and hiatal area on
      Valsalva. Delivery mode of the second birth seemed to have little effect on
      changes observed between follow-ups, although there was a trend towards increased
      bladder-neck descent in women after vaginal delivery. On reviewing patients
      diagnosed with avulsion at their 2-3-year visit and comparing them with findings
      at the first follow-up visit, we found identical (normal) findings in 87 cases.
      In five there was an unchanged avulsion. In one case, findings had improved from
      complete to partial avulsion. There was one new avulsion, in a patient who had
      delivered her first baby by emergency Cesarean section and her second by vacuum
      delivery. CONCLUSIONS: A second pregnancy and delivery do not seem to have a
      major effect on bladder support and/or levator function. However, we documented a
      case of major levator trauma after VBAC. The issue of pelvic floor trauma after
      VBAC may have to be investigated further.

PMID- 24311468
TI  - Let's "face" it: time to introduce yourself to patients.

PMID- 24311467
TI  - Decrease of circulating SAA is correlated with reduction of abdominal SAA
      secretion during weight loss.
AB  - OBJECTIVE: The study goal was to determine the effect of weight loss (WL) alone
      and with aerobic exercise (WL + AEX) on serum amyloid A (SAA) levels and adipose
      SAA secretion from gluteal and abdominal depots. METHODS: Ninety-six overweight
      or obese postmenopausal women undertook a 6-month WL alone (n = 47) or with AEX
      training (n = 49) (6 months WL and WL + AEX are considered WL when groups were
      combined). Their serum SAA levels, body weight, and adipose SAA secretion ex vivo
      from gluteal and abdominal depot were measured before and after WL interventions.
      RESULTS: The participants lost an average of 8% body weight with a 10% decrease
      of serum SAA. Serum SAA levels remained significantly correlated with body weight
      before and after WL. However, the changes of serum SAA level did not correlate
      with changes of body weight. The gluteal adipose tissue secreted ~50% more SAA
      than the abdominal tissue, but the changes of abdominal, but not gluteal, SAA
      secretion correlated (R(2) = 0.19, p < 0.01) with those of serum SAA levels
      during WL. CONCLUSIONS: No linear correlation between the decrease in systemic
      SAA and WL was found. There is a depot-dependent difference in adipose SAA
      secretion and abdominal SAA secretion, which may partially account for the
      systemic SAA reduction during WL.

PMID- 24311469
TI  - Non-overlapping 22q11.2 microdeletions in patients with oculo-auriculo-vertebral
      spectrum.

PMID- 24311470
TI  - Stereocontrol of all-carbon quaternary centers through enantioselective
      desymmetrization of meso primary diols by organocatalyzed acyl transfer.
AB  - The symmetry breaking of meso primary diols bearing a tetrahydropyran ring was
      employed, using catalytic asymmetric acyl transfer, to control all-carbon
      quaternary stereocenters. The planar chiral Fu DMAP catalyst was used in this
      reaction to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a
      synergic effect combining a desymmetrization step and a kinetic resolution.
      Moreover, a beneficial effect was exhibited by C6F6 solvent, yielding the first
      example of an organocatalyzed asymmetric acyl transfer. The desymmetrized
      monoesters were then used to obtain, after a straightforward ring opening
      sequence, complex polyketide building blocks bearing all-carbon quaternary
      stereocenters.

PMID- 24311471
TI  - Periventricular nodular heterotopia and transverse limb reduction defect in a
      woman with interstitial 11q24 deletion in the Jacobsen syndrome region.
AB  - Jacobsen syndrome (JS) is a disorder of developmental delay, growth retardation,
      thrombocytopenia, dysmorphic features, and cardiac abnormalities, among other
      congenital anomalies. JS is caused by contiguous gene deletion in distal
      chromosome 11q, generally varying in size from 7 to 20 Mb. Periventricular
      nodular heterotopia (PVNH) is a neuronal migration disorder in which neurons are
      abnormally located in nodules along the edges of the lateral ventricles. PVNH can
      also be seen with other congenital anomalies, including a recurrent association
      with distal limb defects. Transverse limb defects have previously been reported
      in two patients with JS. We report on a patient with a 3.162 Mb interstitial
      deletion at chromosome region 11q24 overlapping the region commonly affected in
      JS. The patient had PVNH and a transverse limb reduction defect, with minimal
      typical findings of JS. This is the first report of PVNH associated with a
      microdeletion at chromosome 11q and may represent an expansion of the phenotypic
      spectrum associated with JS. This is the third report of transverse limb
      reduction defects in association with JS, supporting a widening of the skeletal
      phenotypic spectrum in JS to include more severe limb anomalies. ETS1 is proposed
      as a candidate gene for involvement in limb anomalies in JS.

PMID- 24311472
TI  - Blockade of microglial KATP -channel abrogates suppression of inflammatory
      mediated inhibition of neural precursor cells.
AB  - Microglia positively affect neural progenitor cell physiology through the release
      of inflammatory mediators or trophic factors. We demonstrated previously that
      reactive microglia foster K(ATP) -channel expression and that blocking this
      channel using glibenclamide administration enhances striatal neurogenesis after
      stroke. In this study, we investigated whether the microglial K(ATP) -channel
      directly influences the activation of neural precursor cells (NPCs) from the
      subventricular zone using transgenic Csf1r-GFP mice. In vitro exposure of NPCs to
      lipopolysaccharide and interferon-gamma resulted in a significant decrease in
      precursor cell number. The complete removal of microglia from the culture or
      exposure to enriched microglia culture also decreased the precursor cell number.
      The addition of glibenclamide rescued the negative effects of enriched microglia
      on neurosphere formation and promoted a ~20% improvement in precursor cell
      number. Similar results were found using microglial-conditioned media from
      isolated microglia. Using primary mixed glial and pure microglial cultures,
      glibenclamide specifically targeted reactive microglia to restore neurogenesis
      and increased the microglial production of the chemokine monocyte chemoattractant
      protein-1 (MCP-1). These findings provide the first direct evidence that the
      microglial K(ATP) -channel is a regulator of the proliferation of NPCs under
      inflammatory conditions.

PMID- 24311473
TI  - Ultrasound estimation of birth weight in twin pregnancy: comparison of biometry
      algorithms in the STORK multiple pregnancy cohort.
AB  - OBJECTIVES: The aims of this study were first, to ascertain the accuracy of
      formulae for ultrasonographic birth-weight estimation in twin compared with
      singleton pregnancies and second, to assess the accuracy of sonographic
      examination in the prediction of birth-weight discordance in twin pregnancies.
      METHODS: This was a retrospective cohort study including both singleton and twin
      pregnancies. Routine biometry was recorded and estimated fetal weight (EFW)
      calculated using 33 different formulae. Only pregnancies that delivered within 48
      h of the ultrasound scan were included (4280 singleton and 586 twin fetuses).
      Differences between the EFW and actual birth weight (ABW) were assessed by
      percentage error, accuracy in predictions within +/- 10% and +/- 15% of error and
      use of the Bland-Altman method. The accuracy of prediction of the different cut
      offs of birth-weight discordance in twin pregnancies was also assessed using the
      area under the receiver-operating characteristics curve (AUC). RESULTS: The
      overall mean absolute percentage error was <= 10% for 25 formulae in singleton
      pregnancies compared with three formulae in twin pregnancies. The overall
      predictions within +/- 10% and +/- 15% of the ABW were 62.2% and 81.5% in
      singleton and 49.7% and 68.5% in twin pregnancies, respectively. When t e
      formulae were categorized according to the biometric parameters included, those
      based on a combination of head, abdomen and femur measurements showed the lowest
      mean absolute percentage error, in both singleton and twin pregnancies. The
      predictive accuracy for 25% birth-weight discordance using the Hadlock 2 formula,
      as assessed by the AUC, was 0.87. CONCLUSIONS: Ultrasound estimation of birth
      weight is less accurate in twin than in singleton pregnancies. Formulae that
      include a combination of head, abdomen and femur measurements perform best in
      both singleton and twin pregnancies.

PMID- 24311474
TI  - Attitudes toward Arab ascendance: Israeli and global perspectives.
AB  - Arab nations are decades behind many other previously colonized nations in
      developing stronger economies, more democratic institutions, and more autonomy
      and self-government, in part as a result of external interference. The year 2011
      brought the potential for greater Arab autonomy through popular uprisings against
      autocratic governments in Tunisia, Egypt, and Yemen, and through the Palestinian
      request for state recognition by the United Nations. We examined the psychology
      of support for Arab ascendancy among adults in 14 nations in the Balkans, the
      Middle East, Asia, Oceania, Europe, and North America. We predicted and found
      that people low on social dominance orientation endorsed forming an independent
      Palestinian state and desired that the Arab uprisings succeed. Rejection of
      ideologies that legitimize outside interference with Arabs mediated this support.
      Measures and model results were robust across world regions. We discuss
      theoretical implications regarding the advent of new ideologies and extending
      social dominance theory to address international relations. 

PMID- 24311475
TI  - What does physical rotation reveal about mental rotation?
AB  - In a classic psychological science experiment, Shepard and Metzler (1971)
      discovered that the time participants took to judge whether two rotated abstract
      block figures were identical increased monotonically with the figures' relative
      angular disparity. They posited that participants rotate mental images to achieve
      a match and that mental rotation recruits motor processes. This interpretation
      has become central in the literature, but until now, surprisingly few researchers
      have compared mental and physical rotation. We had participants rotate virtual
      Shepard and Metzler figures mentally and physically; response time, accuracy, and
      real-time rotation data were collected. Results suggest that mental and physical
      rotation processes overlap and also reveal novel conclusions about physical
      rotation that have implications for mental rotation. Notably, participants did
      not rotate figures to achieve a match, but rather until they reached an off-axis
      canonical difference, and rotational strategies markedly differed for judgments
      of whether the figures were the same or different. 

PMID- 24311476
TI  - Power anomalies in testing mediation.
AB  - Two rather surprising anomalies relating to statistical power occur in testing
      mediation. First, in a model with no direct effect for which the total effect and
      indirect effect are identical, the power for the test of the total effect can be
      dramatically smaller than the power for the test of the indirect effect. Second,
      when there is a direct effect of a causal variable on the outcome controlling for
      the mediator, the power of the test of the indirect effect is often considerably
      greater than the power of the test of the direct effect, even when the two are of
      the same magnitude. We try to explain the reasons for these anomalies and how
      they affect practice. 

PMID- 24311477
TI  - Point-and-shoot memories: the influence of taking photos on memory for a museum
      tour.
AB  - Two studies examined whether photographing objects impacts what is remembered
      about them. Participants were led on a guided tour of an art museum and were
      directed to observe some objects and to photograph others. Results showed a photo
      taking-impairment effect: If participants took a photo of each object as a whole,
      they remembered fewer objects and remembered fewer details about the objects and
      the objects' locations in the museum than if they instead only observed the
      objects and did not photograph them. However, when participants zoomed in to
      photograph a specific part of the object, their subsequent recognition and detail
      memory was not impaired, and, in fact, memory for features that were not zoomed
      in on was just as strong as memory for features that were zoomed in on. This
      finding highlights key differences between people's memory and the camera's
      "memory" and suggests that the additional attentional and cognitive processes
      engaged by this focused activity can eliminate the photo-taking-impairment
      effect. 

PMID- 24311478
TI  - Emotion strengthens high-priority memory traces but weakens low-priority memory
      traces.
AB  - When people encounter emotional events, their memory for those events is
      typically enhanced. But it has been unclear how emotionally arousing events
      influence memory for preceding information. Does emotional arousal induce
      retrograde amnesia or retrograde enhancement? The current study revealed that
      this depends on the top-down goal relevance of the preceding information. Across
      three studies, we found that emotional arousal induced by one image facilitated
      memory for the preceding neutral item when people prioritized that neutral item.
      In contrast, an emotionally arousing image impaired memory for the preceding
      neutral item when people did not prioritize that neutral item. Emotional arousal
      elicited by both negative and positive pictures showed this pattern of enhancing
      or impairing memory for the preceding stimulus depending on its priority. These
      results indicate that emotional arousal amplifies the effects of top-down
      priority in memory formation. 

PMID- 24311479
TI  - 2013 IDSA clinical practice guideline for vaccination of the immunocompromised
      host.
AB  - An international panel of experts prepared an evidenced-based guideline for
      vaccination of immunocompromised adults and children. These guidelines are
      intended for use by primary care and subspecialty providers who care for
      immunocompromised patients. Evidence was often limited. Areas that warrant future
      investigation are highlighted. 

PMID- 24311482
TI  - An introduction to the special issue on interplay of crystallography,
      spectroscopy and theoretical methods for solving chemical problems.

PMID- 24311480
TI  - Women who are motivated to eat and discount the future are more obese.
AB  - OBJECTIVE: Food reinforcement and delay discounting (DD) independently predict
      body mass index (BMI), but there is no research studying whether these variables
      interact to improve prediction of BMI. METHODS: BMI, the relative reinforcing
      value of high (PMAXHED ) and low (PMAXLED ) energy dense food, and DD for $10 and
      $100 future rewards (DD10 , DD100 ) were measured in 199 adult females. RESULTS:
      PMAXHED (P = 0.017), DD10 (P = 0.003), and DD100 (P = 0.003) were independent
      predictors of BMI. The interaction of PMAXLED * DD10 (P = 0.033) and DD100 (P =
      0.039), and PMAXHED * DD10 (P = 0.038) and DD100 (P = 0.045) increased the
      variance accounted for predicting BMI beyond the base model controlling for age,
      education, minority status, disinhibition, and dietary restraint. Based on the
      regression model, BMI differed by about 2 BMI units for low versus high food
      reinforcement, by about 3 BMI units for low versus high DD, and by about 4 BMI
      units for those high in PMAXHED , but low in DD versus high in PMAXHED and high
      in DD. CONCLUSION: Reducing DD may help prevent obesity and improve treatment of
      obesity in those who are high in food reinforcement.

PMID- 24311483
TI  - Building a two-dimensional network from mixed-valence copper units held together
      by acetone bridges.
AB  - The mixed-valence supramolecular product di-MU2-acetone-di-MU3-trifluoroacetato
      deca-MU2-trifluoroacetato-octacopper(I)dicopper(II), [Cu10(C2F3O2)12(C3H6O)2] or
      {[Cu(I)4(O2CCF3)4]2-{MU2-OC(CH3)2}2-[Cu(II)2(O2CCF3)4]}, was prepared by co
      deposition of two building units, namely a bis-acetone adduct of
      [Cu(II)2(O2CCF3)4] and a very electrophilic tetranuclear [Cu(I)4(O2CCF3)4]
      complex. The asymmetric unit contains one molecule of the compound with a total
      of ten independent Cu atoms. Acetone molecules serve as bridges between the
      [Cu(II)2(O2CCF3)4] and [Cu(I)4(O2CCF3)4] units. Additionally, the tetracopper(I)
      trifluoroacetate units are involved in intermolecular Cu...O interactions,
      forming a layered two-dimensional network in the extended structure.

PMID- 24311484
TI  - Ru(II)-hydride-trop complexes: X-ray single-crystal determination and quantum
      chemical calculations.
AB  - As part of our search for catalytically active Ru(II)-hydride complexes, we have
      synthesized and crystallographically characterized three different ruthenium
      species, namely dihydrido[(SR)-(10,11-eta)-N-(pyridin-2-ylmethyl-kappaN)-5H
      dibenzo[a,d]cyclohepten-5-amine](triphenylphosphane-kappaP)ruthenium(II)
      tetrahydrofuran monosolvate, [RuH2(C21H18N2)(C18H15P)].C4H8O or (SR)
      [Ru(II)(H)2{N-(pyridin-2-ylmethyl)tropNH}(PPh3)].THF, (1), chlorido{(1SR,2RS)
      N,N'-bis[(10,11-eta)-5H-dibenzo[a,d]cyclohepten-5-amine]ethane-1,2-diamine
      kappa(2)N,N'}hydridoruthenium(II) dimethoxyethane hemisolvate,
      [RuClH(C32H28N2)].0.5C4H10O2 or (1SR,2RS)
      [Ru(II)(H)(Cl){tropNH(CH2)2HNtrop}].DME, (2), and chlorido{(1SR,2RS)-N,N'
      bis[(10,11-eta)-5H-dibenzo[a,d]cyclohepten-5-amine]propane-1,3-diamine
      kappa(2)N,N'}hydridoruthenium(II), [RuClH(C33H30N2)] or (1SR,2RS)
      [Ru(II)(H)(Cl){tropNH(CH2)3HNtrop}], (3), where trop is 5H
      dibenzo[a,d]cycloheptene. In all three complexes, the Ru(II) center resides in an
      octahedral coordination environment. For (1)-(3), the hydride atoms were located
      in a difference Fourier map and were refined freely. In solution, the (1)H NMR
      spectra of all species show the presence of the hydride resonance. Comparison
      with quantum-chemical calculations reveals that the crystallographic data sets
      are plausible. In every case, the prediction is in very good agreement with the
      observed X-ray data. Not only the observed geometry is predicted well but also
      the Ru-H(hydride) bond lengths are reproduced remarkably well. Complexes (1) and
      (2) crystallized in the triclinic P1 space group, while (3) crystallized in the
      tetragonal space group I4(1)/a. For (3), there is disorder of the axial ligands
      producing two isomers (in a 98.7:1.3 ratio). Details of the synthesis,
      characterization, X-ray analysis, and theoretical calculations for complexes (1)
      (3) are presented.

PMID- 24311485
TI  - Bis(1,1,1,5,5,5-hexafluoropentane-2,4-dionato)tetrakis(MU4-1,1,1,5,5,5
      hexafluoropentane-2,2,4,4-tetraolato)copper(II)octatin(II): a prospective
      precursor for Cu-doped SnO2 films.
AB  - The crystal structure of a tin-rich heterometallic supramolecular product,
      [CuSn8(C5HF6O2)2(C5H2F6O4)4] or [Sn4(hfpt)2-Cu(hfac)2-Sn4(hfpt)2], (I), is
      reported (hfpt is the tetraanion of 1,1,1,5,5,5-hexafluoropentane-2,2,4,4-tetraol
      and hfac is the anion of 1,1,1,5,5,5-hexafluoropentane-2,4-dione). Reaction
      between tin(II) tetraolate, [Sn4(hfpt)2], and copper(II) beta-diketonate,
      [Cu(hfac)2], was utilized for the preparation of (I). The asymmetric unit
      consists of the whole [Sn4(hfpt)2] unit and half of a [Cu(hfac)2] unit, with the
      Cu atom lying on an inversion center. Intermolecular Cu...O interactions from the
      axial positions of copper in [Cu(hfac)2] and O atoms of the hfpt ligand in
      [Sn4(hfpt)2] mediate the formation of a sandwich-type structure for (I).
      Additional intermolecular Sn...O interactions between neighbouring [Sn4(hfpt)2]
      units complete a two-dimensional network.

PMID- 24311486
TI  - Powder diffraction: what's in a name?
AB  - The development of powder diffraction is briefly described; the extent of this
      development from studies of metals to protein crystal structures shows that
      powder diffraction is at the cutting edge of crystallography. A new name
      'polycrystallography' is proposed for these endeavours. 

PMID- 24311487
TI  - NMR diffusion: an update.
AB  - NMR diffusion methods continue to attract increasing attention from practising
      chemists. This short article summarizes some of the more recent developments and
      highlights the areas in which these methods are finding application,
      specifically: estimating molecular volumes; investigating the degree of
      aggregation (especially in salts); studying host-guest interactions; recognizing
      hydrogen bonds; and directly proving the presence and extent of ion pairing. 

PMID- 24311488
TI  - Structure, magnetism and colour in simple bis(phosphine)nickel(II) dihalide
      complexes: an experimental and theoretical investigation.
AB  - The complex [1,2-bis(di-tert-butylphosphanyl)ethane
      kappa(2)P,P']diiodidonickel(II), [NiI2(C18H40P2] or (dtbpe-kappa(2)P)NiI2, [dtbpe
      is 1,2-bis(di-tert-butylphosphanyl)ethane], is bright blue-green in the solid
      state and in solution, but, contrary to the structure predicted for a blue or
      green nickel(II) bis(phosphine) complex, it is found to be close to square planar
      in the solid state. The solution structure is deduced to be similar, because the
      optical spectra measured in solution and in the solid state contain similar
      absorptions. In solution at room temperature, no (31)P{(1)H} NMR resonance is
      observed, but the very small solid-state magnetic moment at temperatures down to
      4 K indicates that the weak paramagnetism of this nickel(II) complex can be
      ascribed to temperature independent paramagnetism, and that the complex has no
      unpaired electrons. The red [1,2-bis(di-tert-butylphosphanyl)ethane
      kappa(2)P,P']dichloridonickel(II), [NiCl2(C18H40P2] or (dtbpe-kappa(2)P)NiCl2, is
      very close to square planar and very weakly paramagnetic in the solid state and
      in solution, while the maroon [1,2-bis(di-tert-butylphosphanyl)ethane
      kappa(2)P,P']dibromidonickel(II), [NiBr2(C18H40P2] or (dtbpe-kappa(2)P)NiBr2, is
      isostructural with the diiodide in the solid state, and displays paramagnetism
      intermediate between that of the dichloride and the diiodide in the solid state
      and in solution. Density functional calculations demonstrate that distortion from
      an ideal square plane for these complexes occurs on a flat potential energy
      surface. The calculations reproduce the observed structures and colours, and
      explain the trends observed for these and similar complexes. Although theoretical
      investigation identified magnetic-dipole-allowed excitations that are
      characteristic for temperature-independent paramagnetism (TIP), theory predicts
      the molecules to be diamagnetic. 

PMID- 24311489
TI  - Solid-state photochemistry of molecular photo-switchable species: the role of
      photocrystallographic techniques.
AB  - Over the last 30 years, the single-crystal photocrystallographic technique has
      been developed to determine the three-dimensional crystal and molecular
      structures of metastable species which have been generated in the crystal
      photochemically. Transition-metal complexes that have been investigated using
      this methodology include complexes that contain nitrosyl, dinitrogen, sulfur
      dioxide and nitrite ligands, all of which form new linkage isomers in the solid
      state when photoactivated by light of the appropriate wavelength. Both steric and
      electronic factors determine the level of the conversion from the ground-state
      structure to the metastable isomeric structure, and both the 'reaction cavity'
      size and the nature of the intermolecular interactions are shown to be among the
      key factors that influence the percentage conversion. 

PMID- 24311490
TI  - On the possibility for Rb- and Eu-cation ordering in type-I clathrates: synthesis
      and homogeneity range of the novel compounds Rb(8-x)Eu(x)(In,Ge)46 (0.6 <= x <=
      1.8).
AB  - Studies in the Rb-Eu-In-Ge system confirm the existence of the phase Rb(8
      x)Eu(x)(In,Ge)46 (0.6 <= x <= 1.8), crystallizing with the cubic clathrate type-I
      structure. The In and Ge content can be varied, concomitant with changes in the
      Rb-Eu ratio. Two of the three framework sites are occupied by statistical
      mixtures of Ge and In atoms, while the site with the lowest multiplicity is taken
      by the In atoms only. Based on the three refined formulae [heptarubidium europium
      nonaindium heptatriacontagermanide, Rb7.39(3)Eu0.61(3)In8.88(5)Ge37.12(5), and
      two forms of hexarubidium dieuropium decaindium hexatriacontagermanide,
      Rb6.30(3)Eu1.70(3)In9.76(4)Ge36.24(4) and Rb6.24(2)Eu1.76(2)In10.16(5)Ge35.84(5)]
      and the explored different synthetic routes, it can be suggested that the known
      ternary phase Rb8In8Ge38 and the hypothetical quaternary phase Rb6Eu2In10Ge36
      represent the boundaries of the homogeneity range. In the former limiting
      composition, both the (Ge,In)20 and the (Ge,In)24 cages are fully occupied by Rb
      atoms only, whereas Rb6Eu2In10Ge36 has Rb atoms encapsulated in the larger
      tetrakaidecahedra, with Eu atoms filling the smaller pentagonal dodecahedra. For
      the solid solutions Rb(8-x)Eu(x)(In,Ge)46, Rb and Eu are statistically disordered
      in the dodecahedral cage, and the tetrakaidecahedral cage is only occupied by Rb
      atoms.

PMID- 24311491
TI  - Arrangement of Rh3+ ions in fac-triamminetrichloridorhodium from powder data and
      in fac-triamminetrinitratorhodium crystals twinned by merohedry.
AB  - The rhodium complexes [RhCl3(NH3)3], (I), and [Rh(NO3)3(NH3)3], (II), are built
      from octahedral RhX3(NH3)3 units; in (I) they are isolated units, while in (II)
      the units are stacked in columns with partially filled sites for the Rh atoms.
      The octahedra of monoclinic crystals of (I) are linked by N-H...Cl hydrogen bonds
      and the Rh(3+) ions are located on the mirror planes. In the trigonal crystals of
      (II), the discontinuous 'columns' along the threefold axis are linked by N-H...O
      hydrogen bonds. The structure of (I) has been solved using laboratory powder
      diffraction data, the structure of (II) has been solved by single-crystal methods
      using data from a merohedrally twinned sample. Both compounds possess low
      solubility in water.

PMID- 24311492
TI  - Distorted octahedral environments in tricarbonylrhenium(I) complexes of 5-[2
      (2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olate and 5,7-bis[2-(2
      methylphenyl)diazen-1-yl]quinolin-8-olate.
AB  - The Re(I) centres of two Re(I)-tricarbonyl complexes, viz. tricarbonyl(pyridine
      kappaN){5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olato
      kappa(2)N(1),O}rhenium(I), [Re(C23H21N4O)(CO)3], (I), and {5,7-bis[2-(2
      methylphenyl)diazen-1-yl]quinolin-8-olato-kappa(2)N(1),O}tricarbonyl(pyridine
      kappaN)rhenium(I), [Re(C28H23N6O)(CO)3], (II), are facially surrounded by three
      carbonyl ligands, a pyridine ligand and either a 5-[2-(2,4,6
      trimethylphenyl)diazen-1-yl]quinolin-8-olate [in (I)] or a 5,7-bis[2-(2
      methylphenyl)diazen-1-yl]quinolin-8-olate [in (II)] ligand, in a slightly
      distorted octahedral environment. The crystal structure of (I) is stabilized by
      two intermolecular C-H...O interactions and that of (II) is stabilized by three
      intermolecular C-H...O hydrogen-bonding interactions.

PMID- 24311493
TI  - Coordination polymeric structures in the sodium salt of 4-chloro-3-nitrobenzoic
      acid and the sodium and potassium salts of 4-nitroanthranilic acid.
AB  - The structures of the hydrated sodium salts of 4-chloro-3-nitrobenzoic acid
      {poly[aqua(MU4-4-chloro-3-nitrobenzoato)sodium(I)], [Na(C7H3ClNO4)(H2O)]n, (I)}
      and 2-amino-4-nitrobenzoic acid {poly[MU-aqua-aqua(MU3-2-amino-4
      nitrobenzoato)sodium(I)], [Na(C7H5N2O4)(H2O)2]n, (II)}, and the hydrated
      potassium salt of 2-amino-4-nitrobenzoic acid {poly[MU-aqua-aqua(MU5-2-amino-4
      nitrobenzoato)potassium(I)], [K(C7H5N2O4)(H2O)]n, (III)} have been determined and
      their complex polymeric structures described. All three structures are stabilized
      by intra- and intermolecular hydrogen bonding and strong pi-pi ring interactions.
      In the structure of (I), the distorted trigonal bipyrimidal NaO5 coordination
      polyhedron comprises a monodentate water molecule and four bridging carboxylate O
      atom donors, generating a two-dimensional polymeric structure lying parallel to
      (001). Intra-layer hydrogen-bonding associations and strong inter-ring pi-pi
      interactions are present. Structure (II) has a distorted octahedral NaO6
      stereochemistry, with four bridging O-atom donors, two from a single carboxylate
      group and two from a single nitro group and three from the two water molecules,
      one of which is bridging. Na centres are linked through centrosymmetric four
      membered duplex water bridges and through 18-membered duplex head-to-tail ligand
      bridges. Similar centrosymmetric bridges are found in the structure of (III), and
      in both (II) and (III) strong inter-ring pi-pi interactions are found. A two
      dimensional layered structure lying parallel to (010) is generated in (II),
      whereas in (III) the structure is three-dimensional. With (III), the irregular
      KO7 coordination polyhedron comprises a doubly bridging water molecule, a single
      bidentate bridging carboxylate O-atom donor and three bridging O-atom donors from
      the two nitro groups. A three-dimensional structure is generated. These
      coordination polymer structures are among the few examples of metal complexes of
      any type with either 4-chloro-3-nitrobenzoic acid or 4-nitroanthranilic acid. 

PMID- 24311494
TI  - A two-dimensional Cu(I) framework incorporating the 1-phenyl-1H-1,2,3,4-tetrazole
      5-thiol ligand.
AB  - The new two-dimensional coordination polymer, poly[(MU4-1-phenyl-1H-1,2,3,4
      tetrazole-5-thiolato)copper(I)], [Cu(C7H5N4S)]n, has been prepared under
      solvothermal conditions by reacting CuBr with 1-phenyl-1H-1,2,3,4-tetrazole-5
      thiol (Hptt) in an acetonitrile and acetone solution. In the crystal structure,
      each Cu(I) ion is coordinated by two N atoms and two S atoms from four ptt(-)
      ligands, and each ptt(-) ligand links four Cu(I) ions to form two-dimensional
      layers which lie parallel to the (100) plane. These layers stack along the [100]
      direction via van der Waals interactions. 

PMID- 24311495
TI  - (OC-6-13)-difluoridooxidobis(propan-2-ol)(propan-2-olato)vanadium(V).
AB  - The distorted octahedral title complex, [V(V)(C3H7O)(C3H8O)2F2O], was synthesized
      via ligand exchange at [V(V)O(OiPr)3] with aqueous hydrogen fluoride in propan-2
      ol and crystallized from (D)chloroform at 238 K after a few weeks. Crystal
      structure determination shows two C1-symmetric moieties to be present in the
      asymmetric unit, forming infinite chains along [100] via hydrogen bonds. The
      compound provides the first crystal structure containing the [VF2O(OiPr)] motif. 

PMID- 24311496
TI  - A three-dimensional chiral crystal structure constructed from a chiral triazolate
      ligand showing an SrSi2 topology: poly[bis(MU3-3,5-diethyl-1,2,4-triazolato
      kappa(3)N(1):N(2):N(4))trisilver nitrate].
AB  - In the title metal-organic framework (MOF), {[Ag3(C6H10N3)2]NO3}n, the Ag(I)
      cation is coordinated by two N atoms from two different 3,5-diethyl-1,2,4
      triazolate (detz) ligands in a linear configuration. Each Ag(I) cation is then
      connected to two adjacent Ag(I) cations via a MU3-N(1):N(2):N(4)-detrz ligand,
      resulting in a three-dimensional chiral silver-triazolate structure showing an
      SrSi2 (srs) net with 10(3) topology. 

PMID- 24311497
TI  - The coordination chemistry of two symmetric fluorene-based organic ligands with
      cuprous chloride.
AB  - Two novel symmetric fluorene-based ligands, namely, 2,7-bis(1H-imidazol-1-yl)-9,9
      dimethyl-9H-fluorene [L1 or (I), C21H18N4] and 2,7-bis(1H-imidazol-1-yl)-9,9
      dipropyl-9H-fluorene (L2), have been used to construct the coordination polymers
      catena-poly[[dichloridodicopper(I)(Cu-Cu)]-MU-2,7-bis(1H-imidazol-1-yl)-9,9
      dimethyl-9H-fluorene], [Cu2Cl2(C21H18N4)]n, (II), and catena-poly[[tetra-MU2
      chlorido-tetracopper(I)]-bis[MU-2,7-bis(1H-imidazol-1-yl)-9,9-dipropyl-9H
      fluorene]], [Cu4Cl4(C25H26N4)2]n, (III). There are three types of C-H...N
      hydrogen bonds in (I), resulting a two-dimensional network in the ab plane,
      including a chiral helical chain along the b axis. Compounds (II) and (III) are
      related one-dimensional polymers. In both, Cu(I) atoms connect the symmetric
      ligands (L1 or L2) into a one-dimensional chain. In (II), the {[Cu(I)Cl2](-)}
      unit, acting as a co-anion, adheres to the one-dimensional chain through a weak
      Cu...Cu interaction. However, in (III), the {[Cu(I)2Cl4](2-)} unit links two
      different chains into a one-dimensional rope-ladder-type chain. In addition,
      there are C-H...Cl hydrogen bonds and pi-pi interactions in the extended
      structures of (II) and (III), the difference is that the chains in (II) are
      linked into a two-dimensional network while the chains in (III) are stacked into
      a three-dimensional framework.

PMID- 24311498
TI  - Calcium and strontium salts of (glycinato-kappa(2)N,O)oxidobis(peroxido
      kappa(2)O,O')vanadate(V) tetrahydrate.
AB  - The title salts calcium (glycinato-kappa(2)N,O)oxidobis(peroxido
      kappa(2)O,O')vanadate(V) tetrahydrate, Ca[VO(O2)2(NH2CH2COO)].4H2O, and strontium
      (glycinato-kappa(2)N,O)oxidobis(peroxido-kappa(2)O,O')vanadate(V) tetrahydrate,
      Sr[VO(O2)2(NH2CH2COO)].4H2O, crystallized at pH ca 7.4 with similar lattice
      parameters. The glycinate anion acts as a bidentate N,O-chelating ligand, and the
      V atom has a pentagonal bipyramidal geometry, with two eta(2)-peroxo groups and
      the glycinate N atom in the equatorial plane, and one terminal oxo and a
      glycinate O atom at the axial positions. The H atoms of three of the four water
      molecules in the strontium salt exhibited disorder over three positions for each
      molecule. 

PMID- 24311499
TI  - Supramolecular architecture of metal-organic frameworks involving dinuclear
      copper paddle-wheel complexes.
AB  - The two centrosymmetric dinuclear copper paddle-wheel complexes tetrakis(MU-4
      hydroxybenzoato-kappa(2)O:O')bis[aquacopper(II)] dimethylformamide disolvate
      dihydrate, [Cu2(C7H5O3)4(H2O)2].2C3H7NO.2H2O, (I), and tetrakis(MU-4
      methoxybenzoato-kappa(2)O:O')bis[(dimethylformamide-kappaO)copper(II)],
      [Cu2(C8H7O3)4(C3H7NO)2], (II), crystallize with half of the dinuclear paddle
      wheel cage unit in the asymmetric unit and, in addition, complex (I) has one
      dimethylformamide (DMF) and one water solvent molecule in the asymmetric unit. In
      both (I) and (II), two Cu(II) ions are bridged by four syn,syn-eta(1):eta(1):MU
      carboxylate groups, showing a paddle-wheel cage-type structure with a square
      pyramidal coordination geometry. The equatorial positions of (I) and (II) are
      occupied by the carboxylate groups of 4-hydroxy- and 4-methoxybenzoate ligands,
      and the axial positions are occupied by aqua and DMF ligands, respectively. The
      three-dimensional supramolecular metal-organic framework of (I) consists of three
      different R2(2)(20) and an R4(4)(36) ring motif formed via O-H...O and OW-HW...O
      hydrogen bonds. Complex (II) simply packs as molecular species.

PMID- 24311500
TI  - Novel three-dimensional coordination polymers of lanthanides with sulfate and
      oxydiacetic acid.
AB  - Three three-dimensional coordination polymers, viz. poly[[diaqua-MU4-oxydiacetato
      di-MU4-sulfato-dipraseodymium(III)] hemihydrate],
      [Pr2(C4H4O5)(SO4)2(H2O)2].0.5H2O, (I), poly[[diaquadi-MU3-oxydiacetato-MU3
      sulfato-dineodymium(III)] 1.32-hydrate], [Nd2(C4H4O5)2(SO4)(H2O)2].1.32H2O, (II),
      and poly[[diaquadi-MU3-oxydiacetato-MU3-sulfato-disamarium(III)] 1.32-hydrate],
      [Sm2(C4H4O5)2(SO4)(H2O)2].1.32H2O, (III), were obtained by hydrothermal reactions
      of the respective lanthanide oxides and ZnSO4 with oxydiacetic acid (odaH2). The
      Nd(3+) and Sm(3+) compounds form isomorphous crystal structures in which the
      lanthanide cations are nine-coordinate, having a tricapped trigonal prismatic
      coordination. The Pr(3+) compound has an entirely different crystal structure in
      which two types of coordination polyhedra are observed, viz. nine-coordinate
      (trigonal prism) and ten-coordinate (bicapped square antiprism). The sulfate
      anions show various coordination modes, one of which has only rarely been
      observed crystallographically to date. 

PMID- 24311502
TI  - 4,4'-{Diazenediylbis[(1,4-phenylene)bis(carbonyloxy)]}bis(2,2,6,6
      tetramethylpiperidinyloxidanyl): the first crystal structure determination from
      powder data of a nitroxide radical.
AB  - The title compound, C32H42N4O6, is a novel nitroxide radical used for pulsed
      electron-electron double resonance (PELDOR) spectroscopy. Its crystal structure
      was determined from laboratory X-ray powder diffraction data. The attractive
      forces between the molecules in the crystal structure are mainly of dispersive
      nature. A special interaction of the nitroxide radicals was not observed. 

PMID- 24311501
TI  - A polymorphic form of 4,4-dimethyl-8-methylene-3-azabicyclo[3.3.1]non-2-en-2-yl 3
      indolyl ketone, an indole alkaloid extracted from Aristotelia chilensis (maqui).
AB  - The title compound [systematic name: (4,4-dimethyl-8-methylene-3
      azabicyclo[3.3.1]non-2-en-2-yl)(1H-indol-3-yl)methanone], C20H22N2O, (II), was
      obtained from mother liquors extracted from Aristotelia chilensis (commonly known
      as maqui), a native Chilean tree. The compound is a polymorphic form of that
      obtained from the same source and reported by Watson, Nagl, Silva, Cespedes &
      Jakupovic [Acta Cryst. (1989), C45, 1322-1324], (Ia). The molecule consists of an
      indolyl ketone fragment and a nested three-ring system, with both groups linked
      by a C-C bridge. Comparison of both forms shows that they do not differ in their
      gross features but in the relative orientation of the two ring systems, due to
      different rotations around the bridge, as measured by the O=C-C=N torsion angle
      [130.0 (7) degrees  in (Ia) and 161.6 (2) degrees  in (II)]. The resulting slight
      conformational differences are reflected in a number of intramolecular contacts
      being observed in (II) but not in (Ia). Regarding intermolecular interactions,
      both forms share a similar N-H...O synthon but with differing hydrogen-bonding
      strength, leading in both cases to C(6) catemers with different chain motifs.
      There are marked differences between the two forms regarding colour and the
      (de)localization of a double bond, which allows speculation about the possible
      existence of different variants of this type of molecule.

PMID- 24311504
TI  - (9E)-9-benzylidene-2-methylsulfanyl-5-phenyl-6,7,8,9-tetrahydropyrimido[4,5
      b]quinolin-4(3H)-one: a hydrogen-bonded R2(2)(8) dimer.
AB  - In the molecule of the title compound, C25H21N3OS, which was prepared by mild
      oxidation of the corresponding 5,6,7,8,9,10-hexahydro analogue, the fused
      carbocyclic ring adopts an envelope conformation. Pairs of molecules are linked
      into cyclic centrosymmetric dimers by pairs of inversion-related N-H...O hydrogen
      bonds.

PMID- 24311503
TI  - Tosylate salts of the anticancer drug lapatinib.
AB  - Two tosylate salts of an anticancer drug lapatinib, viz. a monotosylate
      [systematic name: ({5-[4-({3-chloro-4-[(3
      fluorophenyl)methoxy]phenyl}amino)quinazolin-6-yl]furan-2-yl}methyl)[2
      (methylsulfonyl)ethyl]azanium 4-methylbenzenesulfonate],
      C29H27ClFN4O4S(+).C7H7O3S(-), (I), and a ditosylate [systematic name: 4-({3
      chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)-6-]5-({[2
      (methylsulfonyl)ethyl]azaniumyl}methyl)furan-2-yl[quinazolin-1-ium bis(4
      methylbenzenesulfonate)], C29H28ClFN4O4S(2+).2C7H7O3S(-), (II), were obtained
      during crystallization attempts for polymorphism. In both structures, the
      lapatinib cation is in a distorted U-like conformation and the tosylate anion is
      clamped between the aniline N atom and methylamine N atom through N-H...O
      hydrogen bonds, forming an R2(2)(15) ring motif. The 4-anilinoquinazoline ring
      system is essentially planar in (I), while it is twisted in (II), controlled by
      an intramolecular C-H...N interaction. In (I), alternating cations and anions are
      linked by N-H...O hydrogen bonds into C2(2)(6) chains. These chains are linked by
      cations in a helical manner. The presence of the additional tosylate anion in
      (II) results in the formation of one-dimensional tapes of fused hydrogen-bonded
      rings through N-H...O and C-H...O interactions. These studies augment our
      understanding of the role of nonbonded interactions in the solid state, which is
      useful for correlation to the physicochemical properties of drug products.

PMID- 24311505
TI  - 4-Oxo-N-phenyl-4H-chromene-2-carboxamide and of a new polymorph of 7-methoxy-4
      oxo-N-p-tolyl-4H-chromene-2-carboxamide and its hemihydrate.
AB  - 4-Oxo-N-phenyl-4H-chromene-2-carboxamide, C16H11NO3, crystallizes in the space
      group P2(1)/n and its derivative 7-methoxy-4-oxo-N-p-tolyl-4H-chromene-2
      carboxamide, C18H15NO4, forms two polymorphs which crystallize in the space
      groups P2(1)/c and P1. The structures have an anti-rotamer conformation about the
      C-N bond; however, the amide O atom can be either trans- or cis-related to the O
      atom of the pyran ring. The latter compound also crystallizes as a hemihydrate,
      C18H15NO4.0.5H2O, in the space group C2/c. This compound has a similar structure
      to that of the unsolvated compound.

PMID- 24311506
TI  - Imidazolidin-2-one: pseudosymmetry and twinning.
AB  - The title compound, C3H6N2O, crystallizes with imposed twofold symmetry in the
      space group I4(1)/a. The five-membered ring displays a half-chair conformation. N
      H...O hydrogen bonds connect the molecules to form R2(2)(8) rings and thence
      ribbons parallel to the a and b axes. These intersect via O2H2 rings involving
      longer H...O contacts. The crystal was merohedrally twinned. Preliminary
      indications of the higher symmetry space group I4(1)/amd, which would require the
      ring to be planar, proved to be incorrect. A previous brief report of the
      structure in Fdd2 is also probably incorrect.

PMID- 24311507
TI  - Two-dimensional hydrogen-bonded supramolecular networks in the compounds of
      benzene-1,2,4,5-tetracarboxylic acid (pyromellitic acid) with 2,2'-biimidazole
      and 4,4'-dimethyl-2,2'-bipyridine.
AB  - Two products from the proton-transfer reactions of benzene-1,2,4,5
      tetracarboxylic acid (pyromellitic acid, PMA) with 2,2'-biimidazole and 4,4'
      dimethyl-2,2'-bipyridine, namely 2,2'-biimidazole-3,3'-diium 2,5-dicarboxybenzene
      1,4-dicarboxylate, C6H8N4(2+),C10H4O8(2-), (I), and 4-methyl-2-(4-methylpyridin-2
      yl)pyridinium 2,4,5-tricarboxybenzoate monohydrate, C12H13N2(+).C10H5O8(-).H2O,
      (II), have been prepared and their structures determined. Both compounds
      crystallize in the space group P1. The asymmetric unit of (I) is composed of two
      independent ion pairs. Both the 2,2'-biimidazole-3,3'-diium dication and the
      PMA(2-) anion are located on special positions (inversion centres). The
      protonated 2,2'-biimidazole-3,3'-diium ring H atoms are involved in hydrogen
      bonding with carboxylate O atoms to form one-dimensional hydrogen-bonded chain
      structures. Adjacent chains are further linked via carboxyl-carboxyl O-H...O
      hydrogen bonding, resulting in a two-dimensional supramolecular sheet with the
      R6(5)(34) motif extending in the (1-21) plane. In (II), classical O-H...O
      hydrogen-bond-linked anion-anion units are extended into a one-dimensional chain
      running parallel to the [100] direction, giving an R2(2)(8)R4(4)(30) motif. The
      chains are connected by water-carboxyl O-H...O hydrogen bonds to form a two
      dimensional network parallel to the (011) plane. The 4-methyl-2-(4-methylpyridin
      2-yl)pyridinium cations lie between the two-dimensional supramolecular layers
      linked via N-H...O hydrogen-bonding interactions.

PMID- 24311508
TI  - Head-to-tail square-shaped cyclic hydrogen bonds leading to dimeric aggregates:
      1,8-dibenzoyl-2,7-dihydroxynaphthalene and a comparison with its analogous
      benzoylnaphthalene.
AB  - The title compound, C24H16O4, crystallized with two independent molecules in the
      asymmetric unit. Both carbonyl groups in these molecules form intramolecular O
      H...O=C hydrogen bonds with neighbouring hydroxy groups, affording six-membered
      cyclic structures. In the crystal, dimeric aggregates arise from two
      intermolecular O-H...O=C hydrogen bonds between both independent molecules,
      forming head-to-tail square-shaped cyclic ...O...H...O...H... hydrogen bonds.
      These dimeric aggregates are connected into layers in the bc plane by
      intermolecular (naphthalene)C-H...O=C interactions. On the other hand, the
      analogous compound bearing methoxy groups at the 2- and 7-positions of the
      naphthalene ring, namely 1,8-dibenzoyl-2,7-dimethoxynaphthalene [Nakaema et al.
      (2008). Acta Cryst. E64, o807], forms a three-dimensional molecular network via C
      H...O=C and pi-pi interactions between the benzoyl groups. These results show
      that the intramolecular O-HvO=C hydrogen bonds in the title compound control the
      orientations of the benzoyl groups and thus promote the formation of the cyclic
      intermolecular O-H...O=C interactions involving the same donor and acceptor
      groups in pairs of molecules.

PMID- 24311509
TI  - Three-dimensional hydrogen-bonded assembly in 2,2'-disulfanylidene-5,5'
      biimidazolidinylidene-4,4'-dione-dimethylformamide-water (3/2/4).
AB  - The title compound, 3C6H4N4O2S2.2C3H7NO.4H2O, comprises three 2,2'
      disulfanylidene-5,5'-biimidazolidinylidene-4,4'-dione molecules, two
      dimethylformamide molecules and four water molecules arranged around a
      crystallographic inversion centre. The non-H atoms within the 5,5'
      biimidazolidinylidene molecule are coplanar and these molecules aggregate through
      N-H...S hydrogen-bonding interactions with cyclic motifs [graph set R2(2)(8)],
      giving two-dimensional ribbon structures which are close to being parallel. The
      two independent water molecules associate to form centrosymmetric cyclic hydrogen
      bonded (H2O)4 tetrameric units [graph set R4(4)(8)]. The ribbon structures extend
      along the a axis and are linked through the water tetramers and the
      dimethylformamide molecules by a combination of two- and three-centre hydrogen
      bonds, giving an overall three-dimensional structure.

PMID- 24311510
TI  - Two polymorphs of 2-ethyl-3-hydroxy-6-methylpyridinium hydrogen N-acetyl-L
      glutamate from powder diffraction data.
AB  - The title salt, C8H12NO(+).C7H10NO5(-), crystallizes in two polymorphic
      modifications, viz. monoclinic (M) and orthorhombic (O). The crystal structures
      of both polymorphic modifications have been established from laboratory powder
      diffraction data. The crystal packing motifs in the two polymorphs are different,
      but the conformations of the anions are generally similar. In M, the anions are
      linked by pairs of hydrogen bonds of the N-H...O and O-H...O types into chains
      along the b-axis direction, and neighbouring molecules within the chain are
      related by the 21 screw axis. The cations link these chains via O-H...O and N
      H...O hydrogen bonds into layers parallel to (001). In O, the anions are linked
      by O-H...O hydrogen bonds into helices along [001], and neighbouring molecules
      within the helix are related by the 21 screw axis. The neighbouring helical turns
      are linked by N-H...O hydrogen bonds. The cations link the helices via O-H...O
      and N-H...O hydrogen bonds, thus forming a three-dimensional network.

PMID- 24311511
TI  - Transannular S...N interactions in 10-ethynyl-10H-phenothiazine 5-oxide and 5,5
      dioxide.
AB  - The title compounds, C14H9NOS, (1), and C14H9NO2S, (2), are oxidation products of
      the parent compound 10-ethynyl-10H-phenothiazine. They differ with respect to
      transannular interactions, the intramolecular S...N contact being shorter in (2).
      Intermolecular Csp-H...O hydrogen bonds were detected in both crystals, and (1)
      was found to form stronger hydrogen bonds. These results are in agreement with
      the lower acidity of Csp-H in (2), caused by an increase in pi-electron density
      due to the transannular S...N interaction.

PMID- 24311512
TI  - Isolation, pharmacological activity and structure determination of physalin B and
      5beta,6beta-epoxyphysalin B isolated from Congolese Physalis angulata L.
AB  - Physalis angulata L., an annual herb from the Solanaceae family, is widely used
      in popular medicine in tropical countries to treat a variety of diseases. Two
      products, (X) and (Y), were isolated from a crude CH2Cl2 extract of dried
      Congolese Physalis angulata L. plants and crystallized from acetone for structure
      elucidation. Compound (X) corresponds to a physalin B dimer acetone solvate
      hydrate (2C28H30O9.C3H6O.0.22H2O), while compound (Y) crystallizes as a mixed
      crystal containing two physalin B molecules which overlap with 5beta,6beta
      epoxyphysalin B, also known as physalin F, and one acetone molecule in the
      asymmetric unit (1.332C28H30O9.0.668C28H30O10.C3H6O). Antiplasmodial activity,
      cytotoxic activity and selectivity indices were determined for crude extracts and
      the two isolated products (X) and (Y). 

PMID- 24311513
TI  - Intermolecular C-H...O, Cl...Cl and pi-pi interactions in the 2-dichloromethyl
      derivative of vitamin K3.
AB  - The title 1,4-naphthoquinone, 2-dichloromethyl-3-methyl-1,4-dihydronaphthalene
      1,4-dione, C12H8Cl2O2, is a chlorinated derivative of vitamin K3, which is a
      synthetic compound also known as menadione. Molecules of (I) are planar and lie
      on a crystallographic mirror plane (Z' = 0.5) in the space group Pnma. They are
      connected to each other by C-H...O hydrogen bonds, forming two-dimensional layers
      parallel to the ac plane. In addition, Cl...Cl and pi-pi interactions link
      adjacent molecules in different layers, thus forming zigzag ribbons along the b
      axis, such that a three-dimensional architecture is generated.

PMID- 24311514
TI  - SNX8: A candidate gene for 7p22 cardiac malformations including tetralogy of
      fallot.

PMID- 24311515
TI  - Impact of EPA ingestion on COX- and LOX-mediated eicosanoid synthesis in skin
      with and without a pro-inflammatory UVR challenge--report of a randomised
      controlled study in humans.
AB  - SCOPE: Eicosapentaenoic acid (EPA), abundant in oily fish, is reported to reduce
      skin inflammation and provide photoprotection, potential mechanisms include
      competition with arachidonic acid (AA) for metabolism by
      cyclooxygenases/lipoxygenases to less pro-inflammatory mediators. We thus examine
      impact of EPA intake on levels of AA, EPA and their resulting eicosanoids in
      human skin with or without ultraviolet radiation (UVR) challenge. METHODS AND
      RESULTS: In a double-blind randomised controlled study, 79 females took 5 g EPA
      rich or control lipid for 12 wk. Pre- and post-supplementation, red blood cell
      and skin polyunsaturated fatty acids were assessed by GC, and eicosanoids from
      unexposed and UVR-exposed skin by LC-MS/MS. Active supplementation increased red
      blood cell and dermal EPA versus control (both p < 0.001), lowering relative
      AA:EPA content (4:1 versus 15:1 and 5:1 versus 11:1, respectively; both p <
      0.001). Pre-supplementation, UVR increased PGE2, 12-hydroxyeicosatetraenoic
      acids, 12-HEPE (all p < 0.001) and PGE3 (p < 0.05). Post-EPA, PGE2 was reduced in
      unchallenged skin (p < 0.05) while EPA-derived PGE3 (non-sign) and 12-HEPE (p <
      0.01) were elevated post-UVR. Thus, post-EPA, PGE2 :PGE3 was lower in
      unchallenged (12:1 versus 28:1; p < 0.05) and UVR exposed (12:1 versus 54:1; p <
      0.01) skin; 12-hydroxyeicosatetraenoic acids:12-HEPE was lower in UVR-exposed
      skin (3:1 versus 11:1; p < 0.001). CONCLUSION: Dietary EPA augments skin EPA:AA
      content, shifting eicosanoid synthesis towards less pro-inflammatory species, and
      promoting a regulatory milieu under basal conditions and in response to
      inflammatory insult.

PMID- 24311517
TI  - Helicenes with embedded phosphole units in enantioselective gold catalysis.
AB  - This paper discloses the first uses of phosphahelicenes as chiral ligands in
      transition-metal catalysis. Unlike all known helical phosphines used so far in
      catalysis, the phosphorus function of phosphahelicenes is embedded in the helical
      structure itself. This crucial structural feature originates unprecedented
      catalytic behaviors and efficiency. An appropriate design and fine tuning allowed
      both high catalytic activity and good enantiomeric excesses to be attained in the
      gold promoted cycloisomerizations of N-tethered 1,6-enynes and dien-ynes. 

PMID- 24311516
TI  - Arylsulfatase B modulates neurite outgrowth via astrocyte chondroitin-4-sulfate:
      dysregulation by ethanol.
AB  - In utero ethanol exposure causes fetal alcohol spectrum disorders, associated
      with reduced brain plasticity; the mechanisms of these effects are not well
      understood, particularly with respect to glial involvement. Astrocytes release
      factors that modulate neurite outgrowth. We explored the hypothesis that ethanol
      inhibits neurite outgrowth by increasing the levels of inhibitory chondroitin
      sulfate proteoglycans (CSPGs) in astrocytes. Astrocyte treatment with ethanol
      inhibited the activity of arylsulfatase B (ARSB), the enzyme that removes sulfate
      groups from chondroitin-4-sulfate (C4S) and triggers the degradation of C4S,
      increased total sulfated glycosaminoglycans (GAGs), C4S, and neurocan core
      protein content and inhibited neurite outgrowth in neurons cocultured with
      ethanol-treated astrocytes in vitro, effects reversed by treatment with
      recombinant ARSB. Ethanol also inhibited ARSB activity and increased sulfate GAG
      and neurocan levels in the developing hippocampus after in vivo ethanol exposure.
      ARSB silencing increased the levels of sulfated GAGs, C4S, and neurocan in
      astrocytes and inhibited neurite outgrowth in cocultured neurons, indicating that
      ARSB activity directly regulates C4S and affects neurocan expression. In summary,
      this study reports two major findings: ARSB modulates sulfated GAG and neurocan
      levels in astrocytes and astrocyte-mediated neurite outgrowth in cocultured
      neurons; and ethanol inhibits the activity of ARSB, increases sulfated GAG, C4S,
      and neurocan levels, and thereby inhibits astrocyte-mediated neurite outgrowth.
      An unscheduled increase in CSPGs in the developing brain may lead to altered
      brain connectivity and to premature decrease in neuronal plasticity and therefore
      represents a novel mechanism by which ethanol can exert its neurodevelopmental
      effects.

PMID- 24311518
TI  - Surgical intervention for esophageal atresia in patients with trisomy 18.
AB  - Trisomy 18 is a common chromosomal aberration syndrome involving growth
      impairment, various malformations, poor prognosis, and severe developmental delay
      in survivors. Although esophageal atresia (EA) with tracheoesophageal fistula
      (TEF) is a potentially fatal complication that can only be rescued through
      surgical correction, no reports have addressed the efficacy of surgical
      intervention for EA in patients with trisomy 18. We reviewed detailed clinical
      information of 24 patients with trisomy 18 and EA who were admitted to two
      neonatal intensive care units in Japan and underwent intensive treatment
      including surgical interventions from 1982 to 2009. Nine patients underwent only
      palliative surgery, including six who underwent only gastrostomy or both
      gastrostomy and jejunostomy (Group 1) and three who underwent gastrostomy and TEF
      division (Group 2). The other 15 patients underwent radical surgery, including 10
      who underwent single-stage esophago-esophagostomy with TEF division (Group 3) and
      five who underwent two-stage operation (gastrostomy followed by esophago
      esophagostomy with TEF division) (Group 4). No intraoperative death or anesthetic
      complications were noted. Enteral feeding was accomplished in 17 patients, three
      of whom were fed orally. Three patients could be discharged home. The 1-year
      survival rate was 17%: 27% in those receiving radical surgery (Groups 3 and 4);
      0% in those receiving palliative surgery (Groups 1 and 2). Most causes of death
      were related to cardiac complications. EA is not an absolute poor prognostic
      factor in patients with trisomy 18 undergoing radical surgery for EA and
      intensive cardiac management.

PMID- 24311519
TI  - After Angelina and the Supreme Court Decision, where do we go from here? BRCA
      gene testing in Rhode Island's Portuguese population.

PMID- 24311520
TI  - Our children are not a diagnosis: the experience of parents who continue their
      pregnancy after a prenatal diagnosis of trisomy 13 or 18.
AB  - Trisomy 13 and trisomy 18 (T13-18) are associated with high rates of perinatal
      death and with severe disability among survivors. Prenatal diagnosis (PND) may
      lead many women to terminate their pregnancy but some women choose to continue
      their pregnancy. We sent 503 invitations to answer a questionnaire to parents who
      belong to T13 and 18 internet support groups. Using mixed methods, we asked
      parents about their prenatal experience, their hopes, the life of their affected
      child, and their family experience. 332 parents answered questions about 272
      children; 128 experienced PND. These parents, despite feeling pressure to
      terminate (61%) and being told that their baby would likely die before birth
      (94%), chose to continue the pregnancy. Their reasons included: moral beliefs
      (68%), child-centered reasons (64%), religious beliefs (48%), parent-centered
      reasons (28%), and practical reasons (6%). At the time of the diagnosis, most of
      these parents (80%) hoped to meet their child alive. By the time of birth, 25%
      chose a plan of full interventions. A choice of interventions at birth was
      associated with fewer major anomalies (P < 0.05). Parents describe "Special"
      healthcare providers as those who gave balanced and personalized information,
      respected their choice, and provided support. Parents make decisions to continue
      a pregnancy and choose a plan of care for their child according to their beliefs
      and their child's specific medical condition, respectively. Insights from
      parents' perspective can better enable healthcare providers to counsel and
      support families.

PMID- 24311521
TI  - Continuous tissue microarray based identification of cancers with homogeneous
      target expression for successful targeted therapy in clinical routine practice.
AB  - In cancer therapy, the number of drugs targeting cells with characteristic
      molecular aberrations is continuously rising. However, application of these new
      drugs still is limited to a few tumor entities. The aim of this study was to test
      the concept of routinely identifying all possible cancer patients who might
      eventually benefit from targeted therapy. Therefore, all malignant tumors
      routinely submitted to our Institute of Pathology over a period of 4 months were
      brought into a tissue microarray format. Using "in situ" methods, tumors were
      analyzed for HER2, EGFR, and KIT status as examples for potential therapeutic
      target genes. In positive cases, target heterogeneity was excluded by analyzing
      all available large sections. Outside of tumor entities for which targeted drugs
      are already approved, the study revealed six tumors with homogeneously
      distributed HER2 overexpression/amplification (bladder, esophageal and
      colorectal) and seven tumors with homogeneous EGFR amplification (vulvar,
      ovarian, breast, esophageal and laryngeal, and adenocarcinoma of unknown
      primary). A total of 151 tumors showed KIT overexpression but none of seven
      sequenced cases showed KIT mutations. We furthermore report on a 69-year-old
      patient with homogeneously HER2-amplified metastatic colorectal cancer who is
      successfully treated by trastuzumab monotherapy. This study demonstrates that
      tissue microarray based screening for therapeutic target genes in tumors outside
      established indications represents a feasible approach suitable for routine
      application. The successful treatment of one patient with homogeneously HER2
      positive metastatic colorectal cancer argues for the clinical utility of this
      approach at least in carefully selected, homogeneous cancers.

PMID- 24311522
TI  - Multiplexing of novel microsatellite loci for the vulnerable slipper lobster
      Scyllarus arctus (Linnaeus, 1758).
AB  - The marine slipper lobster Scyllarus arctus represents an important economic
      resource in the NE Atlantic, and in some regions it has been severely exploited
      for decades. Even so, the basic aspects of the biology and ecology of S. arctus
      remain largely unknown and there is very little information available for the
      species, especially in terms of stock assessment and population dynamics. The aim
      of this study was to develop novel microsatellite markers using 454 sequencing
      for the slipper lobster S. arctus. Ten novel loci were described and amplified in
      114 individuals using 3 multiplex reactions. Overall, microsatellite loci were
      highly polymorphic, and the number of detected alleles per locus across all
      individuals ranged from 6 to 29. Conservation strategies in the NE Atlantic
      region may consider these novel markers to study the population structure of S.
      arctus throughout its distribution area so that future efforts could be focused
      on identifying scales of connectivity and preserving stocks that have been
      severely depleted.

PMID- 24311523
TI  - Identification and characterization of a basic thaumatin-like protein (TLP 2) as
      an allergen in sapodilla plum (Manilkara zapota).
AB  - SCOPE: Cases of oral allergy syndrome following the ingestion of sapodilla plum
      (Manilkara zapota) have been reported rarely. As the causative allergens are not
      known, the main objective of this study was to identify and characterize the
      important allergens in sapodilla. METHODS AND RESULTS: Allergy to sapodilla was
      diagnosed by case history, skin prick test, and serum allergen-specific IgE. The
      allergen was detected by IgE immunoblotting, purified on SP-Sepharose and
      characterized by native/SDS-PAGE, IEF, MS, and amino acid composition. Several
      cases of allergy to sapodilla fruit were identified; majority of the sapodilla
      allergic subjects (6/7) experienced typical oral allergy syndrome symptoms, and
      allergen-specific IgE to the purified protein was positive. The allergen has a pI
      >=9.5 and high contents of arginine, threonine, glycine, and cysteine. Circular
      dichroism revealed a secondary structure rich in beta sheets/turns. Based on its
      N-terminal sequence of A-T-F-D-I-Q-N-N-C-X-Y-, the allergen (21 578 Da) was
      identified as a thaumatin-like protein by homology. CONCLUSION: The causative
      allergen in sapodilla plum has been identified and characterized as a highly
      basic thaumatin-like protein belonging to the pathogenesis-related protein (PR-5)
      family, which has been recognized as a new family of conserved, cross-reactive
      plant allergens.

PMID- 24311524
TI  - Old and new: evidence-based evaluation of interventions for Graves' Orbitopathy.

PMID- 24311525
TI  - Hypoglycemia in Kabuki syndrome.
AB  - Kabuki syndrome (KS) is a congenital malformation disorder with a spectrum of
      clinical manifestations involving different organs. Until the identification of
      MLL2 gene mutation in 2010, the diagnosis was made only clinically by the
      characteristic facial features with other common and uncommon features.
      Hypoglycemia, although an uncommon feature in KS, is very important to be
      recognized, as early diagnosis and appropriate management will reduce further
      long-term neurologic morbidity in these patients. We report on four patients with
      KS presenting with persistent hypoglycemia. Hyperinsulinemic hypoglycemia was the
      cause of hypoglycemia in two out of four patients and one patient had growth
      hormone deficiency. The mechanism of the hypoglycemia in one patient is still
      unclear. Three out of these four patients were found to have mutation in the MLL2
      gene. Our observations suggest that patients with KS may have hypoglycemia due to
      different mechanisms and that MLL2 gene may have a role in glucose physiology.

PMID- 24311526
TI  - Marfan Syndrome: Clinical, Surgical, and Anesthetic Considerations.
AB  - Marfan syndrome is a multisystem connective tissue disorder, with primary
      involvement of the cardiovascular, ocular, and skeletal systems. This autosomal
      heritable disease is mainly attributable to a defect in the FBN1 gene. Clinical
      diagnosis of Marfan syndrome has been based on the Ghent criteria since 1996. In
      2010, these criteria were updated, and the revised guidelines place more emphasis
      on aortic root dilation, ectopia lentis, and FBN1 mutation testing in the
      diagnostic assessment of Marfan syndrome. Among its many different clinical
      manifestations, cardiovascular involvement deserves special consideration, owing
      to its impact on prognosis. Recent molecular, surgical, and clinical research has
      yielded profound new insights into the pathological mechanisms that ultimately
      lead to tissue degradation and weakening of the aortic wall, which has led to
      exciting new treatment strategies. Furthermore, with the increasing life
      expectancy of patients with Marfan syndrome, there has been a subtle shift in the
      spectrum of medical problems. Consequently, this article focuses on recent
      advances to highlight their potential impact on future concepts of patient care
      from a clinical, surgical, and anesthetic perspective. 

PMID- 24311527
TI  - Classic phenotype of Coffin-Lowry syndrome in a female with stimulus-induced drop
      episodes and a genotype with preserved N-terminal kinase domain.
AB  - An adolescent female presented with intellectual disability, stimulus-induced
      drop episodes (SIDEs), facial characteristics that include wide set eyes, short
      nose with wide columella, full and everted lips with wide mouth and progressive
      skeletal changes: scoliosis, spondylolisthesis and pectus excavatum. These
      findings were suggestive of Coffin-Lowry syndrome (CLS), and this was confirmed
      by the identification of a novel mutation in RPS6KA3, a heterozygous one basepair
      duplication at nucleotide 1570 (c.1570dupA). This mutation occurs within the C
      terminal kinase domain of the protein, and, therefore contradicts the previous
      report that SIDEs is only associated with premature truncation of the protein in
      the N-terminal kinase domain or upstream of this domain. As CLS is X-linked, it
      is unusual for a female to have such a classic phenotype.

PMID- 24311528
TI  - Near-infrared light-mediated photoactivation of a platinum antitumor prodrug and
      simultaneous cellular apoptosis imaging by upconversion-luminescent
      nanoparticles.
AB  - Platinum-based drugs are among the most active antitumor reagents in clinical
      practice; their application is limited by side effects and drug resistance. A
      novel and personalized near-infrared (NIR) light-activated nanoplatform is
      obtained by combining a photoactivatable platinum(IV) prodrug and a caspase
      imaging peptide conjugated with silica-coated upconversion-luminescent
      nanoparticles (UCNPs) for the remote control of antitumor platinum prodrug
      activation, and simultaneously for real-time imaging of apoptosis induced by
      activated cytotoxicity. Upon NIR light illumination, the Pt(IV) prodrug complex
      is activated at the surface of the nanoparticle and active components are
      selectively released which display cytotoxicity against human ovarian carcinoma
      A2780 cells and its cisplatin-resistant variant A2780cis cells. More importantly,
      the caspases enzymes triggered by cytotoxicity would effectively cleave the probe
      peptide, thereby allowing the direct imaging of apoptosis in living cells. 

PMID- 24311529
TI  - In vitro digestion of soluble cashew proteins and characterization of surviving
      IgE-reactive peptides.
AB  - SCOPE: The stability of food allergens to digestion varies. We characterized the
      stability of cashew allergens to digestion by pepsin and trypsin and identified
      IgE-binding epitopes that survive digestion. METHODS AND RESULTS: The ability of
      pepsin and trypsin to digest cashew allergens was assessed with an in vitro
      digestion model. Samples were evaluated by SDS-PAGE, MS, ELISA, and
      immunoblotting to compare IgE binding. Increasing amount of protease resulted in
      greater degradation of higher molecular weight cashew proteins. Among cashew
      proteins, the 2S albumin, Ana o 3, was most resistant to digestion by both pepsin
      and trypsin. MS identified digestion resistant Ana o 3 protein fragments that
      retained reported IgE-binding epitopes. Pretreatment of extracts or purified Ana
      o 3 with reducing agent increased the sensitivity of Ana o 3 to protease
      digestion. Circular dichroism revealed the structure of purified Ana o 3 was
      largely alphahelical and was disrupted following reduction. Ana o 3 reduction
      followed by protease digestion decreased binding of serum IgE from cashew
      allergic patients. Our results indicate that the Ana o 3 disulfide bond dependent
      structure protects the protein from proteolysis. CONCLUSION: Ana o 3 is the
      cashew allergen most likely to survive gastrointestinal digestion intact.

PMID- 24311530
TI  - Age-related biological features of germ cell tumors.
AB  - Germ cell tumors (GCTs) are rare but clinically and pathologically diverse tumors
      that occur in an extensive range of age groups, from children to older adults and
      which include both seminomatous and nonseminomatous tumors. Current clinical
      management for both male and female teenagers and young adults (TYAs) with GCTs
      remains inconsistent, alternating between pediatric and adult multidisciplinary
      oncology teams, based on locally defined age cutoffs. Therefore, we reviewed
      available literature to determine the biological similarities and differences
      between GCTs in young children (0-12 years), TYAs (13-24 years), and older adults
      (>24 years). GCTs arising in pediatric and adult populations in general showed
      marked molecular biological differences within identical histological subtypes,
      whereas there was a distinct paucity of available data for GCTs in the TYA
      population. These findings highlight that clinical management based simply on
      chronological age may be inappropriate for TYA and suggests that the optimal
      future management of GCTs should consider specific molecular biological factors
      in addition to clinical parameters in the context of patient-specific age group
      rather than medical specialty.

PMID- 24311531
TI  - Congenital neutropenia with retinopathy, a new phenotype without intellectual
      deficiency or obesity secondary to VPS13B mutations.
AB  - Over one hundred VPS13B mutations are reported in Cohen syndrome (CS). Most cases
      exhibit a homogeneous phenotype that includes intellectual deficiency (ID),
      microcephaly, facial dysmorphism, slender extremities, truncal obesity,
      progressive chorioretinal dystrophy, and neutropenia. We report on a patient
      carrying two VPS13B splicing mutations with an atypical phenotype that included
      microcephaly, retinopathy, and congenital neutropenia, but neither obesity nor
      ID. RNA analysis of the IVS34+2T_+3AinsT mutation did not reveal any abnormal
      splice fragments but mRNA quantification showed a significant decrease in VPS13B
      expression. RNA sequencing analysis up- and downstream from the IVS57+2T>C
      mutation showed abnormal splice isoforms. In contrast to patients with typical
      CS, who express only abnormal VPS13B mRNA and truncated protein, a dose effect of
      residual normal VPS13B protein possibly explains the incomplete phenotype in the
      patient. This observation emphasizes that VPS13B analysis should be performed in
      cases of congenital neutropenia associated with retinopathy, even in the absence
      of ID, therefore extending the VPS13B phenotype spectrum.

PMID- 24311532
TI  - Hepatoblastoma in a 15-month-old female with trisomy 13.
AB  - Trisomy 13 (T13) is a rare autosomal aneuploidy. Greater than 90% of patients die
      during the first year of life. Malignancies reported in association with T13
      include two cases of Wilms tumor and one case of pilocytic astrocytoma. There is
      no previous report of hepatoblastoma in patients with T13. We report a unique
      case of hepatoblastoma in a 15-month-old female with constitutional T13. Our
      patient was born at 38 weeks gestation and was noted to have phenotypic features
      consistent with T13. Genetic testing confirmed an abnormal karyotype of 47,XX,+13
      in all cells. At fifteen months of age she was noted to have a right hepatic lobe
      mass on a routine follow-up renal ultrasound for hydronephrosis. Serum alpha
      fetoprotein level was 55,300 ng/ml. Staging work-up revealed the absence of
      metastases. She underwent a complete surgical resection with right hepatic
      lobectomy. Histopathology was consistent with hepatoblastoma, mixed epithelial
      and mesenchymal type. She had a protracted postoperative course complicated by
      Enterobacter aerogenes urosepsis, a significant biloma, chronic pancreatitis, and
      apneic episodes of uncertain etiology. She received four courses of doxorubicin
      monotherapy without any severe or unexpected toxicity. She continues to be in
      remission 8 months following diagnosis. This is the first reported case of
      hepatoblastoma in a child with constitutional T13. This may represent a non
      random association, as somatic trisomy of chromosome 13 in hepatoblastoma tumors
      has been previously described in the literature. Prolonged survival may have
      allowed for hepatoblastoma to present in our patient.

PMID- 24311533
TI  - Lignans 7-hydroxymatairesinol and 7-hydroxymatairesinol 2 exhibit anti
      inflammatory activity in human aortic endothelial cells.
AB  - SCOPE: In the present study, we evaluated the anti-inflammatory properties of
      several plant lignans most commonly distributed in foods. 7-Hydroxymatairesinol
      (HMR) and its major isomer 7-hydroxymatairesinol 2 (HMR2), lariciresinol,
      secoisolariciresinol, and pinoresinol, isolated from Norway spruce knots were
      examined. METHODS AND RESULTS: We investigated the anti-inflammatory effects of
      lignans on tumor necrosis factor-alpha-treated human aortic endothelial cells by
      measuring the expression of intracellular adhesion molecule-1 and vascular cell
      adhesion molecule-1 by cell ELISA and the adhesion of U937 monocytes to activated
      endothelial cells using a cell adhesion assay. Among the lignans studied, HMR and
      HMR2 significantly reduced intracellular adhesion molecule-1 and vascular cell
      adhesion molecule-1 levels as well as the adhesion of U937 to endothelial cells.
      To further characterize the molecular mechanisms involved in this regulation, the
      effect of HMR and HMR2 on nuclear factor-kappaB, SAPK/c-Jun NH2-terminal kinase
      and extracellular signal regulated kinase phosphorylation was assessed.
      CONCLUSION: Our results demonstrated that the lignans HMR and HMR2, dominant in
      cereals such as in wheat, triticale, oat, barley, millet, corn bran, and in
      amaranth whole grain, exhibit strong anti-inflammatory properties in endothelial
      cells, at least in part, through attenuation of nuclear factor-kappaB and
      extracellular signal regulated kinase phosphorylation.

PMID- 24311534
TI  - Cucurbit[7]uril: a high-affinity host for encapsulation of amino saccharides and
      supramolecular stabilization of their alpha-anomers in water.
AB  - Cucurbit[7]uril (CB[7]), an uncharged and water-soluble macrocyclic host, binds
      protonated amino saccharides (D-glucosamine, D-galactosamine, D-mannosamine and 6
      amino-6-deoxy-D-glucose) with excellent affinity (Ka =10(3) to 10(4)  M(-1) ).
      The host-guest complexation was confirmed by NMR spectroscopy, isothermal
      titration calorimetry (ITC), and MALDI-TOF mass spectral analyses. NMR analyses
      revealed that the amino saccharides, except D-mannosamine, are bound as alpha
      anomers within the CB[7] cavity. ITC analyses reveal that CB[7] has excellent
      affinity for binding amino saccharides in water. The maximum affinity was
      observed for D-galactosamine hydrochloride (Ka =1.6*10(4)  M(-1) ). Such a strong
      affinity for any saccharide in water using a synthetic receptor is unprecedented,
      as is the supramolecular stabilization of an alpha-anomer by the host. 

PMID- 24311535
TI  - Metabolism of aildenafil in vivo in rats and in vitro in mouse, rat, dog, and
      human liver microsomes.
AB  - Aildenafil, 1-{[3-(6, 7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4, 3-d]
      primidin-5-yl)-4-ethoxyphenyl] sulfonyl}-cis-3, 5-dimethylpiperazine, a
      phosphodiesterase type V enzyme inhibitor (PDE5I), is under development for
      treatment of erectile dysfunction (ED). The purpose of this study was to
      elucidate metabolism of aildenafil in vivo in rats and in vitro in mouse, rat,
      dog, and human liver microsomes. Thirty-one phase I metabolites have been found
      by LTQ/Orbitrap hybrid mass spectrometry in rat urine, faeces, and bile after
      oral administration. Major biotransformation pathways of aildenafil included N
      dealkylation of the piperazine ring, hydroxylation and dehydrogenation, aliphatic
      hydroxylation and loss of alkyl group of piperazine ring. Minor pathways involved
      hydroxylation on the phenyl ring, pyrazole N-demethylation, O-deethylation, loss
      of piperazine ring (cleavage of N-S bond) and dehydrogenation on the piperazine
      ring. Similar metabolic pathways of aildenafil were observed in the incubations
      of liver microsomes from mouse, rat, and dog as well as from human. The depletion
      rate of parent drug in mouse and rat liver microsomes was significantly different
      from that in human liver microsomes. The cytochrome P450 reaction phenotyping
      analysis was conducted using isozyme-specific inhibitors. The results indicated
      that CYP3A was the main isoenzyme involved in oxidative metabolism of aildenafil.
      Overall, these in vitro and in vivo findings should provide valuable information
      on possible metabolic behaviours of aildenafil in humans.

PMID- 24311537
TI  - A cross-sectional study of victimisation of bullying among schoolchildren in
      Sweden: background factors and self-reported health complaints.
AB  - AIM: To examine background factors for bullying and associations between bullying
      victimisation and health problems. METHODS: A cross-sectional study on all pupils
      in grades 7 and 9 in a Swedish county was conducted in 2011 (n=5248). Data have
      been analysed with bi- and multivariate models. RESULTS: 14% of the children
      reported that they had been bullied during the past 2 months. Background factors
      for bullying were: gender (girls more often); age (younger students more often);
      disability/disease; high body mass index, and having parents born abroad. There
      were strong associations between being bullied and poor health and self-harm.
      Associations with poor general health for boys and girls and mental health
      problems for girls showed stronger associations with higher frequency of bullying
      than with lower. For boys, physical bullying had stronger correlations with poor
      general health than written-verbal bullying. CONCLUSIONS: Bullying is a serious
      public health problem among young people and healthcare professionals have an
      important task in identifying exposed children. Children who are "different" are
      more exposed to bullying, which implies that school personnel, parents, and other
      adults in these children's social networks can play an important role in paying
      attention to and preventing the risk of bullying.

PMID- 24311536
TI  - Cross-cultural validation of a simple self-report instrument of physical activity
      in immigrants from the Middle East and native Swedes.
AB  - AIM: To investigate cross-cultural validity of a simple self-report instrument of
      physical activity intended to be used in Swedish health care. METHODS: A
      validation study performed in 599 Iraqis (58% men) and 553 Swedes (53% men) aged
      30-75 years living in the city of Malmo, Sweden. The self-report instrument by
      the Swedish National Board of Health and Welfare was compared to corresponding
      measures assessed from accelerometry as reference. RESULTS: The agreement between
      the methods in assessing the participants as sufficiently/insufficiently
      physically active (cut-point 150 min/week) was 65% in the Iraqis and 52% in the
      Swedes (p<0.001). The proportion disagreement where the self-reported physical
      activity was sufficient but insufficient according to the accelerometry was 26%
      and 45% in Iraqis and Swedes, respectively. Physical activity time (min/week) was
      overestimated by self-report compared to accelerometry by 71% in the Iraqis and
      115% in the Swedes (p<0.001). The smallest and largest overestimation was seen in
      Iraqi (57%) and Swedish (139%) women, respectively. The deviation of the self
      report instrument compared to accelerometry was related to the physical activity
      level, as the overestimation mainly occurred at lower physical activity.
      CONCLUSIONS: The self-report instrument proposed by the Swedish National Board of
      Health and Welfare may overestimate the proportion sufficiently physically
      active, but to an extent depending on cultural background and gender.

PMID- 24311538
TI  - A case of Robin sequence, microgastria, radiohumeral synostosis, femoral
      deficiency, and other unusual findings: a newly recognized syndrome?
AB  - In this report, we describe an 8-year-old male with Robin sequence, bilateral
      radiohumeral synostosis, microgastria, cryptorchidism, dislocated hips, proximal
      femoral deficiency, and an autism spectrum disorder. This combination of findings
      has not been previously reported. Features of particular interest are the
      radiohumeral synostosis and microgastria, both of which are rare defects, and to
      our knowledge, have not been reported to occur together. We propose that the
      patient has a newly recognized syndrome consisting of the aforementioned
      features, the etiology of which is unknown.

PMID- 24311539
TI  - Robust surface reconstruction of teeth from raw pointsets.
AB  - This paper discusses a 3D robust dental surface reconstruction method. The
      surface reconstruction method usually consists of the following stages: mesh
      generation, surface registration, and surface merging. A large amount of noise
      will be accumulated after these three processes especially for the dental model
      with many sharp features of high curvature. To obtain an accurate dental surface,
      this paper first strengthens the mesh generation and the surface registration
      using optimal parameters. Then, a 3D robust dental surface reconstruction is
      performed by iteratively executing the smallest univalue segment assimilating
      nucleus filtering method and the surface attraction method. Finally, virtual
      scanning and real scanning models are introduced to validate the accuracy of the
      presented method. The experiments show that our method can robustly reconstruct
      the 3D dental model.

PMID- 24311540
TI  - Late diagnosis of lateral meningocele syndrome in a 55-year-old woman with
      symptoms of joint instability and chronic musculoskeletal pain.
AB  - Lateral meningocele syndrome (LMS) is a rare hereditary connective tissue
      disorder characterized by pan-spinal meningoceles, specific facial dysmorphism,
      skeletal and soft tissue abnormalities, and hypotonia and/or muscle weakness. LMS
      has been observed in eleven patients with two instances of vertical transmission,
      and seven sporadic cases with an age at diagnosis ranging from 25 months to 33
      years. We report on a further observation of LMS in a 55-year-old woman
      presenting with a long history of joint instability, chronic musculoskeletal
      pain, and iatrogenic bladder and anorectal dysfunction due to irreversible nerve
      damage after surgical excision of a meningeal cyst. Her clinical characteristics
      are compared with those of previously reported patients, as well as two further
      cases originally diagnosed with Hajdu-Cheney and Ehlers-Danlos syndromes, but
      displaying typical features of LMS.

PMID- 24311541
TI  - Marine neurotoxins: state of the art, bottlenecks, and perspectives for mode of
      action based methods of detection in seafood.
AB  - Marine biotoxins can accumulate in fish and shellfish, representing a possible
      threat for consumers. Many marine biotoxins affect neuronal function essentially
      through their interaction with ion channels or receptors, leading to different
      symptoms including paralysis and even death. The detection of marine biotoxins in
      seafood products is therefore a priority. Official methods for control are often
      still using in vivo assays, such as the mouse bioassay. This test is considered
      unethical and the development of alternative assays is urgently required.
      Chemical analyses as well as in vitro assays have been developed to detect marine
      biotoxins in seafood. However, most of the current in vitro alternatives to
      animal testing present disadvantages: low throughput and lack of sensitivity
      resulting in a high number of false-negative results. Thus, there is an urgent
      need for the development of new in vitro tests that would allow the detection of
      marine biotoxins in seafood products at a low cost, with high throughput combined
      with high sensitivity, reproducibility, and predictivity. Mode of action based in
      vitro bioassays may provide tools that fulfil these requirements. This review
      covers the current state of the art of such mode of action based alternative
      assays to detect neurotoxic marine biotoxins in seafood. 

PMID- 24311542
TI  - Endoscopic anatomy of the middle ethmoidal artery.
AB  - BACKGROUND: The purpose of this study was to describe the incidence of the middle
      ethmoidal artery and its anatomical nuances via an endoscopic endonasal approach.
      METHODS: A cadaveric study was performed on 22 adult specimens. First, a frontal
      sinusotomy and ethmoidectomy were performed via an endoscopic endonasal approach
      in order to fully expose the anterior skull base. Subsequently, the lamina
      papyracea and the bone of the canals covering the ethmoidal neurovascular bundles
      were removed to identify the anterior, middle, and posterior ethmoidal arteries.
      Presence, laterality, and location of the middle ethmoidal artery were recorded.
      RESULTS: A total of 14 middle ethmoidal arteries were identified (10 right and 4
      left), among 44 sides (22 specimens), accounting for an incidence of 31.8%.
      Bilateral middle ethmoidal arteries were found in 3 of 22 specimens (14%).
      Endonasal endoscopy features of the middle ethmoidal artery were noted.
      CONCLUSION: This is the first study assessing the anatomical features of the
      middle ethmoidal arteries from an endonasal endoscopic perspective. The findings
      of this research have clinical significance in guiding surgeries that involve the
      medial orbital wall, intractable epistaxis, and anterior skull base pathologies,
      as well as endoscopic endonasal surgeries.

PMID- 24311543
TI  - What is Antrodia sensu stricto?
AB  - The polypore genus Antrodia (Polyporales, Basidiomycota) in the strict sense
      consists of a small number of species grouped around the type species A. serpens
      in phylogenetic analyses. This distinct clade (Antrodia sensu stricto in our
      view) contains species of the Antrodia heteromorpha complex, A. macra coll. and
      Antrodia mappa (formerly Postia mappa). Nuclear rDNA ITS and tef1 data show that
      the Antrodia heteromorpha species complex includes four species: A. heteromorpha
      sensu stricto (mostly on gymnosperms, large pores and spores), A. serpens (on
      angiosperms in Europe, resupinate, smaller pores but large spores), A. favescens
      (smaller pores and spores, pileate species in North America, formerly known as
      Trametes sepium), and A. tanakai (a close kin of A. favescens in Eurasia).
      Antrodia albida is a synonym of A. heteromorpha sensu stricto. We combine A.
      mappa, A. favescens and A. tanakai in Antrodia and designate neotypes for A.
      albida and A. heteromorpha, and an epitype for A. serpens. We also compare the
      morphologically similar but distantly related A. albidoides and A. mellita, and
      conclude that A. macrospora and A. subalbidoides are synonyms of A. albidoides. 

PMID- 24311544
TI  - Plant polyphenols in the treatment of age-associated diseases: revealing the
      pleiotropic effects of icariin by network analysis.
AB  - Polyphenols are a broad class of compounds. Some are ingested in substantial
      quantities from nutritional sources, more are produced by medicinal plants, and
      some of them are taken as drugs. It is becoming clear, that a single polyphenol
      is impacting several cellular pathways. Thus, a network approach is becoming
      feasible, describing the interaction of a single polyphenol with cellular
      networks. Here we have selected icariin to draw a prototypic network of icariin
      activities. Icariin appears to be a promising drug to treat major age-related
      diseases, like neurodegeneration, memory and depressive disorders, chronic
      inflammation, diabetes, and osteoporosis. It interacts with several relevant
      pathways, like PDE, TGF-beta, MAPK, PPAR, NOS, IGF, Sirtuin, and others. Such
      networks will be useful to future comparative studies of complex effects of
      polyphenols. 

PMID- 24311545
TI  - Allergy education in otolaryngology residency: a survey of program directors and
      residents.
AB  - BACKGROUND: The purpose of this study was to survey program directors of the
      accredited otolaryngology residency programs and resident attendees of the 2013
      American Academy of Otolaryngic Allergy (AAOA) Basic/MOC Course regarding
      resident education and participation as well as assessment of competency in
      otolaryngic allergy and immunotherapy. METHODS: A multiple-choice questionnaire
      was sent to all accredited otolaryngology residency training programs in the
      United States as part of resident attendance at the 2013 AAOA CORE Basic/MOC
      Course. Following this, a similar multiple-choice survey was sent to all resident
      attendees from the programs that responded positively. RESULTS: Program directors
      reported that 73% of their academic institutions offer allergy testing and
      immunotherapy. More PDs than residents indicated that residents participate in
      allergy practice and perform/interpret skin testing and in vitro testing, and
      more residents (85%) than program directors (63%) reported inadequate or no
      allergy training. Program directors and residents equally indicated that
      residents do not calculate immunotherapy vial formulations or administer
      immunotherapy injections. The majority of program directors indicated that
      resident competency in allergy was assessed through direct observation, whereas
      residents more commonly perceived that no assessment of competency was being
      performed for any portion of allergy practice. CONCLUSION: This survey
      demonstrates a discrepancy between program directors and residents regarding
      resident involvement and adequacy of training in the allergy practice. Although
      the majority of otolaryngology residencies report offering otolaryngic allergy
      services and education, the vast majority of residents report inadequate allergy
      training and less participation in an allergy practice compared to the majority
      of program directors.

PMID- 24311546
TI  - Diagnosis of filariasis on cytology: a series of 24 cases.
AB  - Filariasis has a worldwide distribution, with a special predilection for tropical
      and subtropical areas. The microfilaria wanders in lymphatics and can be
      accidentally trapped in the needle during fine-needle aspiration cytology, thus
      leading to its incidental detection. This is a retrospective study of 24 cases of
      microfilarial infestation diagnosed on cytology. Accurate recognition and
      detection of the parasite leads to the institution of specific treatment and
      prevents chronic manifestations of the disease. 

PMID- 24311547
TI  - Improving paediatric tuberculosis and HIV clinical record keeping: the use of
      audit and a structured pro forma in a South African regional level hospital.
AB  - We report on the impact of revisions made to an existing pro forma facilitating
      routine assessment and the management of paediatric HIV and tuberculosis (TB) in
      KwaZulu-Natal, South Africa. An initial documentation audit in 2010 assessed 25
      sets of case notes for the documentation of 16 select indicators based on
      national HIV and TB guidelines. Using the findings of this initial audit, the
      existing case note pro forma was revised. The introduction of the revised pro
      forma was accompanied by training and a similar repeat audit was undertaken in
      2012. This demonstrated an overall improvement in documentation. The three
      indicators that improved most were documentation of maternal HIV status, child's
      HIV status and child's TB risk assessment (all P < 0.001). This study suggests
      that tailor-made documentation pro formas may have an important role to play in
      improving record keeping in low-resource settings. 

PMID- 24311548
TI  - Leptospirosis and dengue fever: a predictive model for early differentiation
      based on clinical and biochemical parameters.
AB  - Leptospirosis and dengue fever are increasingly seen as causes of tropical
      febrile illness and often are clinically indistinguishable. This two-year
      prospective study from a tertiary care centre comprised 200 patients including 68
      men (mean 34.8 years) with dengue and 73 (mean 46.19 years) with leptospirosis.
      Oliguria, icterus, muscle tenderness, anaemia, leukocytopenia, thrombocytopenia,
      elevated erythrocyte sedimentation rate (ESR), acute renal failure (ARF) and
      hypoalbuminaemia appeared more commonly in leptospirosis in comparison to dengue.
      Eighteen per cent mortality was observed in leptospirosis compared to one per
      cent in dengue. ARF, hyperbilirubinaemia, acute respiratory distress syndrome
      (ARDS), creatine kinase (CK) elevation and thrombocytopenia were predictors of
      death in leptospirosis and thrombocytopenia, ARDS and ARF predictors of death in
      dengue. On receiver operating characteristics (ROC) analysis, leucocytosis
      >11000/mm(3), ESR >40 mm, serum creatinine >2 mg/dL, total serum bilirubin >2
      mg/dL, CK >500 U/L and serum albumin <3 mg/dL were more likely to be an
      indication of leptospirosis at presentation compared to dengue. 

PMID- 24311549
TI  - Evaluating the feasibility of complex interventions in mental health services:
      standardised measure and reporting guidelines.
AB  - BACKGROUND: The feasibility of implementation is insufficiently considered in
      clinical guideline development, leading to human and financial resource wastage.
      AIMS: To develop (a) an empirically based standardised measure of the feasibility
      of complex interventions for use within mental health services and (b) reporting
      guidelines to facilitate feasibility assessment. METHOD: A focused narrative
      review of studies assessing implementation blocks and enablers was conducted with
      thematic analysis and vote counting used to determine candidate items for the
      measure. Twenty purposively sampled studies (15 trial reports, 5 protocols) were
      included in the psychometric evaluation, spanning different interventions types.
      Cohen's kappa (kappa) was calculated for interrater reliability and test-retest
      reliability. RESULTS: In total, 95 influences on implementation were identified
      from 299 references. The final measure - Structured Assessment of FEasibility
      (SAFE) - comprises 16 items rated on a Likert scale. There was excellent
      interrater (kappa = 0.84, 95% CI 0.79-0.89) and test-retest reliability (kappa =
      0.89, 95% CI 0.85-0.93). Cost information and training time were the two
      influences least likely to be reported in intervention papers. The SAFE reporting
      guidelines include 16 items organised into three categories (intervention,
      resource consequences, evaluation). CONCLUSIONS: A novel approach to evaluating
      interventions, SAFE, supplements efficacy and health economic evidence. The SAFE
      reporting guidelines will allow feasibility of an intervention to be
      systematically assessed.

PMID- 24311550
TI  - Cortisol awakening response and subsequent depression: prospective longitudinal
      study.
AB  - BACKGROUND: Some studies have found an association between elevated cortisol and
      subsequent depression, but findings are inconsistent. The cortisol awakening
      response may be a more stable measure of hypothalamic-pituitary-adrenal function
      and potentially of stress reactivity. AIMS: To investigate whether salivary
      cortisol, particularly the cortisol awakening response, is associated with
      subsequent depression in a large population cohort. METHOD: Young people (aged 15
      years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC)
      collected salivary cortisol at four time points for 3 school days. Logistic
      regression was used to calculate odds ratios for developing depression meeting
      ICD-10 criteria at 18 years. RESULTS: We found no evidence for an association
      between salivary cortisol and subsequent depression. Odds ratios for the cortisol
      awakening response were 1.24 per standard deviation (95% CI 0.93-1.66, P = 0.14)
      before and 1.12 (95% CI 0.73-1.72, P = 0.61) after adjustment for confounding
      factors. There was no evidence that the other cortisol measures, including
      cortisol at each time point, diurnal drop and area under the curve, were
      associated with subsequent depression. CONCLUSIONS: Our findings do not support
      the hypothesis that elevated salivary cortisol increases the short-term risk of
      subsequent depressive illness. The results suggest that if an association does
      exist, it is small and unlikely to be of clinical significance.

PMID- 24311551
TI  - Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain
      structure and attributional style.
AB  - BACKGROUND: A single nucleotide polymorphism (rs7914558) within the cyclin M2
      (CNNM2) gene was recently identified as a common risk variant for schizophrenia.
      The mechanism by which CNNM2 confers risk is unknown. AIMS: To determine the
      impact of the rs7914558 risk 'G' allele [corrected] on measures of
      neurocognition, social cognition and brain structure. METHOD: Patients with
      schizophrenia (n = 400) and healthy controls (n = 160) completed measures of
      neuropsychological function and social cognition. Structural magnetic resonance
      imaging data were also acquired from an overlapping sample of Irish healthy
      controls (n = 159) and an independent sample of Italian patients (n = 82) and
      healthy controls (n = 39). RESULTS: No effects of genotype on neuropsychological
      test performance were observed. However, a dosage effect of the risk allele was
      found for an index of social cognition (i.e. attributional style), such that risk
      status was associated with reduced self-serving bias across groups (GG>AG>AA,
      P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions
      putatively supporting social cognition, risk carriers had relatively increased
      grey matter volume in the right temporal pole and right anterior cingulate cortex
      (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical
      associations between CNNM2 and grey matter volume in anterior cingulate cortex
      were also observed in the Italian schizophrenia and healthy controls samples.
      CONCLUSIONS: Although the biological role of CNNM2 in schizophrenia remains
      unknown, these data suggest that this CNNM2 risk variant rs7914558 may have an
      impact on neural systems relevant to social cognition. How such effects may
      mediate the relationship between genotype and disease risk remains to be
      established.

PMID- 24311552
TI  - Analysis of copy number variations at 15 schizophrenia-associated loci.
AB  - BACKGROUND: A number of copy number variants (CNVs) have been suggested as
      susceptibility factors for schizophrenia. For some of these the data remain
      equivocal, and the frequency in individuals with schizophrenia is uncertain.
      AIMS: To determine the contribution of CNVs at 15 schizophrenia-associated loci
      (a) using a large new data-set of patients with schizophrenia (n = 6882) and
      controls (n = 6316), and (b) combining our results with those from previous
      studies. METHOD: We used Illumina microarrays to analyse our data. Analyses were
      restricted to 520 766 probes common to all arrays used in the different data
      sets. RESULTS: We found higher rates in participants with schizophrenia than in
      controls for 13 of the 15 previously implicated CNVs. Six were nominally
      significantly associated (P<0.05) in this new data-set: deletions at 1q21.1,
      NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader
      Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of
      maternal origin. When combined with published data, 11 of the 15 loci showed
      highly significant evidence for association with schizophrenia (P<4.1*10(-4)).
      CONCLUSIONS: We strengthen the support for the majority of the previously
      implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and
      0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV
      screening may be clinically appropriate given the high rate of known deleterious
      mutations in the disorder and the comorbidity associated with these heritable
      mutations.

PMID- 24311553
TI  - Moderators of remission with interpersonal counselling or drug treatment in
      primary care patients with depression: randomised controlled trial.
AB  - BACKGROUND: Despite depressive disorders being very common there has been little
      research to guide primary care physicians on the choice of treatment for patients
      with mild to moderate depression. AIMS: To evaluate the efficacy of interpersonal
      counselling compared with selective serotonin reuptake inhibitors (SSRIs), in
      primary care attenders with major depression and to identify moderators of
      treatment outcome. METHOD: A randomised controlled trial in nine centres (DEPICS,
      Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The
      primary outcome was remission of the depressive episode (defined as a Hamilton
      Rating Scale for Depression score <=7 at 2 months). Daily functioning was
      assessed using the Work and Social Adjustment Scale. Logistic regression models
      were used to identify moderators of treatment outcome. RESULTS: The percentage of
      patients who achieved remission at 2 months was significantly higher in the
      interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P =
      0.021). Five moderators of treatment outcome were found: depression severity,
      functional impairment, anxiety comorbidity, previous depressive episodes and
      smoking habit. CONCLUSIONS: We identified some patient characteristics predicting
      a differential outcome with pharmacological and psychological interventions.
      Should our results be confirmed in future studies, these characteristics will
      help clinicians to define criteria for first-line treatment of depression
      targeted to patients' characteristics.

PMID- 24311554
TI  - GC-MS combined with chemometric techniques for the quality control and original
      discrimination of Curcumae longae rhizome: analysis of essential oils.
AB  - Curcumae longae rhizome is a widely used traditional herb in many countries.
      Various geographical origins of this herb might lead to diversity or instability
      of the herbal quality. The objective of this work was to establish the chemical
      fingerprints for quality control and find the chemical markers for discriminating
      these herbs from different origins. First, chemical fingerprints of essential oil
      of 24 C. longae rhizome from four different geographical origins in China were
      determined by GC-MS. Then, pattern recognition techniques were introduced to
      analyze these abundant chemical data in depth; hierarchical cluster analysis was
      used to sort samples into groups by measuring their similarities, and principal
      component analysis and partial least-squares discriminate analysis were applied
      to find the main chemical markers for discriminating these samples. Curcumae
      longae rhizome from Guangxi province had the highest essential oil yield (4.32 +/
      1.45%). A total of 46 volatile compounds were identified in total. Consistent
      results were obtained to show that C. longae rhizome samples could be
      successfully grouped according to their origins, and turmerone, ar-turmerone, and
      zingiberene were the characteristic components for discriminating these samples
      of various geographical origins and for quality control. This finding revealed
      that fingerprinting analysis based on GC-MS coupled with chemometric techniques
      could provide a reliable platform to discriminate herbs from different origins,
      which is a benefit for quality control. 

PMID- 24311555
TI  - Canonical and non-canonical EcfG sigma factors control the general stress
      response in Rhizobium etli.
AB  - A core component of the alpha-proteobacterial general stress response (GSR) is
      the extracytoplasmic function (ECF) sigma factor EcfG, exclusively present in
      this taxonomic class. Half of the completed alpha-proteobacterial genome
      sequences contain two or more copies of genes encoding sigma(EcfG) -like sigma
      factors, with the primary copy typically located adjacent to genes coding for a
      cognate anti-sigma factor (NepR) and two-component response regulator (PhyR). So
      far, the widespread occurrence of additional, non-canonical sigma(EcfG) copies
      has not satisfactorily been explained. This study explores the hierarchical
      relation between Rhizobium etli sigma(EcfG1) and sigma(EcfG2) , canonical and non
      canonical sigma(EcfG) proteins, respectively. Contrary to reports in other
      species, we find that sigma(EcfG1) and sigma(EcfG2) act in parallel, as nodes of
      a complex regulatory network, rather than in series, as elements of a linear
      regulatory cascade. We demonstrate that both sigma factors control unique yet
      also shared target genes, corroborating phenotypic evidence. sigma(EcfG1) drives
      expression of rpoH2, explaining the increased heat sensitivity of an ecfG1
      mutant, while katG is under control of sigma(EcfG2) , accounting for reduced
      oxidative stress resistance of an ecfG2 mutant. We also identify non-coding RNA
      genes as novel sigma(EcfG) targets. We propose a modified model for GSR
      regulation in R. etli, in which sigma(EcfG1) and sigma(EcfG2) function largely
      independently. Based on a phylogenetic analysis and considering the prevalence of
      alpha-proteobacterial genomes with multiple sigma(EcfG) copies, this model may
      also be applicable to numerous other species. 

PMID- 24311556
TI  - Spoligotyping and drug resistance patterns of Mycobacterium tuberculosis isolates
      from five provinces of Iran.
AB  - Tuberculosis (TB) persists as a public health problem in Iran. Characterization
      of Mycobacterium tuberculosis isolates circulating in this area will contribute
      to understand and control the spread of the strains. The aims of this study were
      to understand the genetic diversity and drug susceptibility of M. tuberculosis
      isolates circulating in Iran and to analyze the relationship between genotype and
      drug resistance. A total of 291 M. tuberculosis isolates collected from TB
      patients were genotyped by spoligotyping. Drug susceptibility testing was
      performed using proportion method. Spoligotyping resulted in 75 distinct
      patterns. 86.2% of isolates were grouped in 35 clusters while the remaining
      isolates were unique. Ural was found to be the most predominant lineage (34.3%)
      followed by Central Asian strain (CAS) (24%), T (18.2%), Manu2 (7.5%) and Latin
      American-Mediterranean (LAM) (6.1%). The five largest clusters were
      Ural/Spoligotype International Type (SIT)127 (15.8%), CAS1/SIT26 (9.2%), T1/SIT53
      (6.1%), T1/SIT284 (5.4%), and CAS1/SIT25 (4.4%). About 5% of isolates had
      multidrug resistance (MDR) and 10% had other resistance. MDR was significantly
      associated with Beijing strains, but not with Ural family. This study highlights
      dominance of Ural, CAS, and T families in Iran. Biogeographic specificity of CAS
      and T families to border provinces of Iran including Sistan-Baluchestan and
      Kermanshah, respectively, suggested that this family strains might be transmitted
      from these regions to other provinces of the country. 

PMID- 24311557
TI  - The rhizosphere microbial community in a multiple parallel mineralization system
      suppresses the pathogenic fungus Fusarium oxysporum.
AB  - The rhizosphere microbial community in a hydroponics system with multiple
      parallel mineralization (MPM) can potentially suppress root-borne diseases. This
      study focused on revealing the biological nature of the suppression against
      Fusarium wilt disease, which is caused by the fungus Fusarium oxysporum, and
      describing the factors that may influence the fungal pathogen in the MPM system.
      We demonstrated that the rhizosphere microbiota that developed in the MPM system
      could suppress Fusarium wilt disease under in vitro and greenhouse conditions.
      The microbiological characteristics of the MPM system were able to control the
      population dynamics of F. oxysporum, but did not eradicate the fungal pathogen.
      The roles of the microbiological agents underlying the disease suppression and
      the magnitude of the disease suppression in the MPM system appear to depend on
      the microbial density. F. oxysporum that survived in the MPM system formed
      chlamydospores when exposed to the rhizosphere microbiota. These results suggest
      that the microbiota suppresses proliferation of F. oxysporum by controlling the
      pathogen's morphogenesis and by developing an ecosystem that permits coexistence
      with F. oxysporum. 

PMID- 24311558
TI  - Isolation and purification of arctigenin from Fructus Arctii by enzymatic
      hydrolysis combined with high-speed counter-current chromatography.
AB  - Enzymatic hydrolysis pretreatment combined with high-speed counter-current
      chromatography for the transformation and isolation of arctigenin from Fructus
      Arctii was successfully developed. In the first step, the extract solution of
      Fructus Arctii was enzymatic hydrolyzed by beta-glucosidase. The optimal
      hydrolysis conditions were 40 degrees C, pH 5.0, 24 h of hydrolysis time, and
      1.25 mg/mL beta-glucosidase concentration. Under these conditions, the content of
      arctigenin was transformed from 2.60 to 12.59 mg/g. In the second step,
      arctigenin in the hydrolysis products was separated and purified by high-speed
      counter-current chromatography with a two-phase solvent system composed of
      petroleum ether/ethyl acetate/methanol/water (10:25:15:20, v/v), and the fraction
      was analyzed by HPLC, ESI-MS, and (1)H NMR spectroscopy. Finally, 102 mg of
      arctigenin with a purity of 98.9% was obtained in a one-step separation from 200
      mg of hydrolyzed sample.

PMID- 24311559
TI  - Newborns with lower levels of circulating polyunsaturated fatty acids (PUFA) are
      abdominally more adipose.
AB  - BACKGROUND: Maternal nutrition is the main source of Poly-Unsaturated Fatty Acids
      (PUFA) for the fetus. PUFA may influence the accumulation of fat in early life.
      OBJECTIVES & METHODS: In 33 breastfed infants born appropriate-for-gestational
      age, we studied whether body composition (judged by absorptiometry at 2 wk and 4
      mo) relates to PUFA levels (assessed by gas chromatography) in the maternal or
      fetal circulation at birth. RESULTS: Abdominal fat at 2 wk associated negatively
      to umbilical-cord levels of separate PUFA (linoleic, arachidonic, eicosapentanoic
      and docosahexaenoic acid; all P between 0.001 and 0.015). Collectively, the
      assessed n-6 PUFA on one hand and the n-3 PUFA on the other hand associated
      negatively to the absolute amount of abdominal fat (in grams; P = 0.001 and P =
      0.002, respectively) and to the relative amount of abdominal fat (fraction of
      total fat; P = 0.001 and P = 0.006, respectively). No other significant
      associations were observed. CONCLUSION: In conclusion, newborns with lower levels
      of circulating PUFA were found to be abdominally more adipose. The mechanisms
      underpinning these associations remain to be determined.

PMID- 24311562
TI  - Testicular microlithiasis an ultrasound dilemma: survey of opinions regarding
      significance and management amongst UK ultrasound practitioners.
AB  - OBJECTIVE: To establish whether there is a consensus regarding the significance
      of testicular microlithiasis and a strategy for managing patients with this
      condition, amongst ultrasound practitioners in the UK. METHODS: An electronic
      questionnaire was distributed to 1482 members of the British Medical Ultrasound
      Society (BMUS), requesting information from ultrasound practitioners involved in
      scrotal ultrasound about their interpretation of the risk associated with
      testicular microlithiasis and their departmental or personal recommendations for
      managing patients with this condition. RESULTS: Responses were obtained from 221
      BMUS members. Analysis demonstrated a wide variation in the significance
      attributed to the discovery of testicular microlithiasis and the risk of
      subsequent development of testicular germ cell tumours. There was also great
      variation in strategies for management of patients with testicular
      microlithiasis, including the need for surveillance ultrasound, amongst
      ultrasound practitioners regardless of their job description. CONCLUSION: Lack of
      consensus shown by this study highlights significant differences across the UK in
      managing patients with testicular microlithiasis and validates the importance of
      guidance currently being formulated by the European Society of Urogenital
      Radiology. ADVANCES IN KNOWLEDGE: We believe that this is the first survey to be
      conducted amongst imaging specialists in the UK regarding testicular
      microlithiasis and demonstrates that there is currently no uniform practice in
      managing patients with this condition.

PMID- 24311563
TI  - Structure-based model for light-harvesting properties of nucleic acid
      nanostructures.
AB  - Programmed self-assembly of DNA enables the rational design of megadalton-scale
      macromolecular assemblies with sub-nanometer scale precision. These assemblies
      can be programmed to serve as structural scaffolds for secondary chromophore
      molecules with light-harvesting properties. Like in natural systems, the local
      and global spatial organization of these synthetic scaffolded chromophore systems
      plays a crucial role in their emergent excitonic and optical properties.
      Previously, we introduced a computational model to predict the large-scale 3D
      solution structure and flexibility of nucleic acid nanostructures programmed
      using the principle of scaffolded DNA origami. Here, we use Forster resonance
      energy transfer theory to simulate the temporal dynamics of dye excitation and
      energy transfer accounting both for overall DNA nanostructure architecture as
      well as atomic-level DNA and dye chemical structure and composition. Results are
      used to calculate emergent optical properties including effective absorption
      cross-section, absorption and emission spectra and total power transferred to a
      biomimetic reaction center in an existing seven-helix double stranded DNA-based
      antenna. This structure-based computational framework enables the efficient in
      silico evaluation of nucleic acid nanostructures for diverse light-harvesting and
      photonic applications. 

PMID- 24311564
TI  - RepeatsDB: a database of tandem repeat protein structures.
AB  - RepeatsDB (http://repeatsdb.bio.unipd.it/) is a database of annotated tandem
      repeat protein structures. Tandem repeats pose a difficult problem for the
      analysis of protein structures, as the underlying sequence can be highly
      degenerate. Several repeat types haven been studied over the years, but their
      annotation was done in a case-by-case basis, thus making large-scale analysis
      difficult. We developed RepeatsDB to fill this gap. Using state-of-the-art repeat
      detection methods and manual curation, we systematically annotated the Protein
      Data Bank, predicting 10,745 repeat structures. In all, 2797 structures were
      classified according to a recently proposed classification schema, which was
      expanded to accommodate new findings. In addition, detailed annotations were
      performed in a subset of 321 proteins. These annotations feature information on
      start and end positions for the repeat regions and units. RepeatsDB is an ongoing
      effort to systematically classify and annotate structural protein repeats in a
      consistent way. It provides users with the possibility to access and download
      high-quality datasets either interactively or programmatically through web
      services.

PMID- 24311565
TI  - mVOC: a database of microbial volatiles.
AB  - Scents are well known to be emitted from flowers and animals. In nature, these
      volatiles are responsible for inter- and intra-organismic communication, e.g.
      attraction and defence. Consequently, they influence and improve the
      establishment of organisms and populations in ecological niches by acting as
      single compounds or in mixtures. Despite the known wealth of volatile organic
      compounds (VOCs) from species of the plant and animal kingdom, in the past, less
      attention has been focused on volatiles of microorganisms. Although fast and
      affordable sequencing methods facilitate the detection of microbial diseases,
      however, the analysis of signature or fingerprint volatiles will be faster and
      easier. Microbial VOCs (mVOCs) are presently used as marker to detect human
      diseases, food spoilage or moulds in houses. Furthermore, mVOCs exhibited
      antagonistic potential against pathogens in vitro, but their biological roles in
      the ecosystems remain to be investigated. Information on volatile emission from
      bacteria and fungi is presently scattered in the literature, and no public and up
      to-date collection on mVOCs is available. To address this need, we have developed
      mVOC, a database available online at http://bioinformatics.charite.de/mvoc. 

PMID- 24311560
TI  - New perspectives on the diversification of the RNA interference system: insights
      from comparative genomics and small RNA sequencing.
AB  - Our understanding of the pervasive involvement of small RNAs in regulating
      diverse biological processes has been greatly augmented by recent application of
      deep-sequencing technologies to small RNA across diverse eukaryotes. We review
      the currently known small RNA classes and place them in context of the
      reconstructed evolutionary history of the RNA interference (RNAi) protein
      machinery. This synthesis indicates that the earliest versions of eukaryotic RNAi
      systems likely utilized small RNA processed from three types of precursors: (1)
      sense-antisense transcriptional products, (2) genome-encoded, imperfectly
      complementary hairpin sequences, and (3) larger noncoding RNA precursor
      sequences. Structural dissection of PIWI proteins along with recent discovery of
      novel families (including Med13 of the Mediator complex) suggest that emergence
      of a distinct architecture with the N-terminal domains (also occurring separately
      fused to endoDNases in prokaryotes) formed via duplication of an ancestral unit
      was key to their recruitment as primary RNAi effectors and use of small RNAs of
      certain preferred lengths. Prokaryotic PIWI proteins are typically components of
      several RNA-directed DNA restriction or CRISPR/Cas systems. However, eukaryotic
      versions appear to have emerged from a subset that evolved RNA-directed RNAi.
      They were recruited alongside RNaseIII domains and RNA-dependent RNA polymerase
      (RdRP) domains, also from prokaryotic systems, to form the core eukaryotic RNAi
      system. Like certain regulatory systems, RNAi diversified into two distinct but
      linked arms concomitant with eukaryotic nucleocytoplasmic compartmentalization.
      Subsequent elaboration of RNAi proceeded via diversification of the core protein
      machinery through lineage-specific expansions and recruitment of new components
      from prokaryotes (nucleases and small RNA-modifying enzymes), allowing for
      diversification of associating small RNAs.

PMID- 24311566
TI  - Identification of truncated forms of U1 snRNA reveals a novel RNA degradation
      pathway during snRNP biogenesis.
AB  - The U1 small nuclear ribonucleoprotein (snRNP) plays pivotal roles in pre-mRNA
      splicing and in regulating mRNA length and isoform expression; however, the
      mechanism of U1 snRNA quality control remains undetermined. Here, we describe a
      novel surveillance pathway for U1 snRNP biogenesis. Mass spectrometry-based RNA
      analysis showed that a small population of SMN complexes contains truncated forms
      of U1 snRNA (U1-tfs) lacking the Sm-binding site and stem loop 4 but containing a
      7-monomethylguanosine 5' cap and a methylated first adenosine base. U1-tfs form a
      unique SMN complex, are shunted to processing bodies and have a turnover rate
      faster than that of mature U1 snRNA. U1-tfs are formed partly from the
      transcripts of U1 genes and partly from those lacking the 3' box elements or
      having defective SL4 coding regions. We propose that U1 snRNP biogenesis is under
      strict quality control: U1 transcripts are surveyed at the 3'-terminal region and
      U1-tfs are diverted from the normal U1 snRNP biogenesis pathway. 

PMID- 24311568
TI  - Stable encapsulation of acrylate esters in networked molecular capsules.
AB  - Reactive acrylate esters were encapsulated in the cavity of networked molecular
      capsules in a single-crystal-to-single-crystal fashion. Owing to the
      encapsulation effect, acrylates inside the capsules do not undergo polymerization
      upon irradiation with UV light or heating, while the guest molecules can be
      quantitatively extracted by treatment with toluene. 

PMID- 24311567
TI  - Parental stress increases body mass index trajectory in pre-adolescents.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Rates of childhood obesity have
      increased since the mid-1970s. Research into behavioural determinants has focused
      on physical inactivity and unhealthy diets. Cross-sectional studies indicate an
      association between psychological stress experienced by parents and obesity in
      pre-adolescents. WHAT THIS STUDY ADDS: We provide evidence of a prospective
      association between parental psychological stress and increased weight gain in
      pre-adolescents. Family-level support for those experiencing chronic stress might
      help promote healthy diet and exercise behaviours in children. OBJECTIVE: We
      examined the impact of parental psychological stress on body mass index (BMI) in
      pre-adolescent children over 4 years of follow-up. METHODS: We included 4078
      children aged 5-10 years (90% were between 5.5 and 7.5 years) at study entry
      (2002-2003) in the Children's Health Study, a prospective cohort study in
      southern California. A multi-level linear model simultaneously examined the
      effect of parental stress at study entry on the attained BMI at age 10 and the
      slope of change across annual measures of BMI during follow-up, controlled for
      the child's age and sex. BMI was calculated based on objective measurements of
      height and weight by trained technicians following a standardized procedure.
      RESULTS: A two standard deviation increase in parental stress at study entry was
      associated with an increase in predicted BMI attained by age 10 of 0.287 kg m(-2)
      (95% confidence interval 0.016-0.558; a 2% increase at this age for a participant
      of average attained BMI). The same increase in parental stress was also
      associated with an increased trajectory of weight gain over follow-up, with the
      slope of change in BMI increased by 0.054 kg m(-2) (95% confidence interval 0.007
      0.100; a 7% increase in the slope of change for a participant of average BMI
      trajectory). CONCLUSIONS: We prospectively demonstrated a small effect of
      parental stress on BMI at age 10 and weight gain earlier in life than reported
      previously. Interventions to address the burden of childhood obesity should
      address the role of parental stress in children.

PMID- 24311569
TI  - Timely deposition of macromolecular structures is necessary for peer review.
AB  - Most of the macromolecular structures in the Protein Data Bank (PDB), which are
      used daily by thousands of educators and scientists alike, are determined by X
      ray crystallography. It was examined whether the crystallographic models and data
      were deposited to the PDB at the same time as the publications that describe them
      were submitted for peer review. This condition is necessary to ensure pre
      publication validation and the quality of the PDB public archive. It was found
      that a significant proportion of PDB entries were submitted to the PDB after peer
      review of the corresponding publication started, and many were only submitted
      after peer review had ended. It is argued that clear description of journal
      policies and effective policing is important for pre-publication validation,
      which is key in ensuring the quality of the PDB and of peer-reviewed literature. 

PMID- 24311570
TI  - Comment on timely deposition of macromolecular structures is necessary for peer
      review by Joosten et al. (2013).

PMID- 24311571
TI  - Comment on on the propagation of errors by Jaskolski (2013).

PMID- 24311572
TI  - Structure and enzymatic mechanism of a moonlighting dUTPase.
AB  - Genome integrity requires well controlled cellular pools of nucleotides. dUTPases
      are responsible for regulating cellular dUTP levels and providing dUMP for dTTP
      biosynthesis. In Staphylococcus, phage dUTPases are also suggested to be involved
      in a moonlighting function regulating the expression of pathogenicity-island
      genes. Staphylococcal phage trimeric dUTPase sequences include a specific
      insertion that is not found in other organisms. Here, a 2.1 A resolution three
      dimensional structure of a phi11 phage dUTPase trimer with complete localization
      of the phage-specific insert, which folds into a small beta-pleated mini-domain
      reaching out from the dUTPase core surface, is presented. The insert mini-domains
      jointly coordinate a single Mg2+ ion per trimer at the entrance to the threefold
      inner channel. Structural results provide an explanation for the role of Asp95,
      which is suggested to have functional significance in the moonlighting activity,
      as the metal-ion-coordinating moiety potentially involved in correct positioning
      of the insert. Enzyme-kinetics studies of wild-type and mutant constructs show
      that the insert has no major role in dUTP binding or cleavage and provide a
      description of the elementary steps (fast binding of substrate and release of
      products). In conclusion, the structural and kinetic data allow insights into
      both the phage-specific characteristics and the generally conserved traits of
      phi11 phage dUTPase.

PMID- 24311573
TI  - Structural basis for a hand-like site in the calcium sensor CatchER with fast
      kinetics.
AB  - Calcium ions, which are important signaling molecules, can be detected in the
      endoplasmic reticulum by an engineered mutant of green fluorescent protein (GFP)
      designated CatchER with a fast off-rate. High resolution (1.78-1.20 A) crystal
      structures were analyzed for CatchER in the apo form and in complexes with
      calcium or gadolinium to probe the binding site for metal ions. While CatchER
      exhibits a 1:1 binding stoichiometry in solution, two positions were observed for
      each of the metal ions bound within the hand-like site formed by the carboxylate
      side chains of the mutated residues S147E, S202D, Q204E, F223E and T225E that may
      be responsible for its fast kinetic properties. Comparison of the structures of
      CatchER, wild-type GFP and enhanced GFP confirmed that different conformations of
      Thr203 and Glu222 are associated with the two forms of Tyr66 of the chromophore
      which are responsible for the absorbance wavelengths of the different proteins.
      Calcium binding to CatchER may shift the equilibrium for conformational
      population of the Glu222 side chain and lead to further changes in its optical
      properties. 

PMID- 24311574
TI  - Staphylococcus aureus thiaminase II: oligomerization warrants proteolytic
      protection against serine proteases.
AB  - Staphylococcus aureus TenA (SaTenA) is a thiaminase type II enzyme that catalyzes
      the deamination of aminopyrimidine, as well as the cleavage of thiamine into 4
      amino-5-hydroxymethyl-2-methylpyrimidine (HMP) and 5-(2-hydroxyethyl)-4
      methylthiazole (THZ), within thiamine (vitamin B1) metabolism. Further, by
      analogy with studies of Bacillus subtilis TenA, SaTenA may act as a regulator
      controlling the secretion of extracellular proteases such as the subtilisin type
      of enzymes in bacteria. Thiamine biosynthesis has been identified as a potential
      drug target of the multi-resistant pathogen S. aureus and therefore all enzymes
      involved in the S. aureus thiamine pathway are presently being investigated in
      detail. Here, the structure of SaTenA, determined by molecular replacement and
      refined at 2.7 A resolution to an R factor of 21.6% with one homotetramer in the
      asymmetric unit in the orthorhombic space group P212121, is presented. The
      tetrameric state of wild-type (WT) SaTenA was postulated to be the functional
      biological unit and was confirmed by small-angle X-ray scattering (SAXS)
      experiments in solution. To obtain insights into structural and functional
      features of the oligomeric SaTenA, comparative kinetic investigations as well as
      experiments analyzing the structural stability of the WT SaTenA tetramer versus a
      monomeric SaTenA mutant were performed. 

PMID- 24311575
TI  - Structural insight into L-ribulose 3-epimerase from Mesorhizobium loti.
AB  - L-Ribulose 3-epimerase (L-RE) from Mesorhizobium loti has been identified as the
      first ketose 3-epimerase that shows the highest observed activity towards
      ketopentoses. In the present study, the crystal structure of the enzyme was
      determined to 2.7 A resolution. The asymmetric unit contained two homotetramers
      with the monomer folded into an (alpha/beta)8-barrel carrying four additional
      short alpha-helices. The overall structure of M. loti L-RE showed significant
      similarity to the structures of ketose 3-epimerases from Pseudomonas cichorii,
      Agrobacterium tumefaciens and Clostridium cellulolyticum, which use ketohexoses
      as preferred substrates. However, the size of the C-terminal helix (alpha8) was
      much larger in M. loti L-RE than the corresponding helices in the other enzymes.
      In M. loti L-RE the alpha8 helix and the following C-terminal tail possessed a
      unique subunit-subunit interface which promoted the formation of additional
      intermolecular interactions and strengthened the enzyme stability. Structural
      comparisons revealed that the relatively small hydrophobic pocket of the enzyme
      around the substrate was likely to be the main factor responsible for the marked
      specificity for ketopentoses shown by M. loti L-RE. 

PMID- 24311576
TI  - Structure of the prolyl-acyl carrier protein oxidase involved in the biosynthesis
      of the cyanotoxin anatoxin-a.
AB  - Anatoxin-a and homoanatoxin-a are two potent cyanobacterial neurotoxins
      biosynthesized from L-proline by a short pathway involving polyketide synthases.
      Proline is first loaded onto AnaD, an acyl carrier protein, and prolyl-AnaD is
      then oxidized to 1-pyrroline-5-carboxyl-AnaD by a flavoprotein, AnaB. Three
      polyketide synthases then transform this imine into anatoxin-a or homoanatoxin-a.
      AnaB was crystallized in its holo form and its three-dimensional structure was
      determined by X-ray diffraction at 2.8 A resolution. AnaB is a homotetramer and
      its fold is very similar to that of the acyl-CoA dehydrogenases (ACADs). The
      active-site base of AnaB, Glu244, superimposed very well with that of human
      isovaleryl-CoA dehydrogenase, confirming previous site-directed mutagenesis
      experiments and mechanistic proposals. The substrate-binding site of AnaB is
      small and is likely to be fitted for the pyrrolidine ring of proline. However, in
      contrast to ACADs, which use an electron-transport protein, AnaB uses molecular
      oxygen as the electron acceptor, as in acyl-CoA oxidases. Calculation of the
      solvent-accessible surface area around the FAD in AnaB and in several homologues
      showed that it is significantly larger in AnaB than in its homologues. A
      protonated histidine near the FAD in AnaB is likely to participate in oxygen
      activation. Furthermore, an array of water molecules detected in the AnaB
      structure suggests a possible path for molecular oxygen towards FAD. This is
      consistent with AnaB being an oxidase rather than a dehydrogenase. The structure
      of AnaB is the first to be described for a prolyl-ACP oxidase and it will
      contribute to defining the structural basis responsible for oxygen reactivity in
      flavoenzymes. 

PMID- 24311577
TI  - Crystallographic identification of an unexpected protein complex in silkworm
      haemolymph.
AB  - The first crystal structure of a complex formed by two storage proteins, SP2 and
      SP3, isolated from their natural source, mulberry silkworm (Bombyx mori L.)
      haemolymph, has been determined. The structure was solved by molecular
      replacement using arylphorin, a protein rich in aromatic amino-acid residues,
      from oak silkworm as the initial model. The quality of the electron-density maps
      obtained from the X-ray diffraction experiment allowed the authors to detect that
      the investigated crystal structure was composed of two different arylphorins: SP2
      and SP3. This discovery was confirmed by N-terminal sequencing. SP2 has been
      extensively studied previously, whereas only a few reports on SP3 are available.
      However, to date no structural studies have been reported for these proteins.
      These studies revealed that SP2 and SP3 exist in the silkworm body as a
      heterohexamer formed by one SP2 trimer and one SP3 trimer. The overall fold,
      consisting of three haemocyanin-like subdomains, of SP2 and SP3 is similar. Both
      proteins contain a conserved N-glycosylation motif in their structures. 

PMID- 24311578
TI  - The landscape of cytokinin binding by a plant nodulin.
AB  - Nodulation is an extraordinary symbiotic interaction between leguminous plants
      and nitrogen-fixing bacteria (rhizobia) that assimilate atmospheric nitrogen (in
      root nodules) and convert it into compounds suitable for the plant host. A class
      of plant hormones called cytokinins are involved in the nodulation process. In
      the model legume Medicago truncatula, nodulin 13 (MtN13), which belongs to the
      pathogenesis-related proteins of class 10 (PR-10), is expressed in the outer
      cortex of the nodules. In general, PR-10 proteins are small and monomeric and
      have a characteristic fold with an internal hydrophobic cavity formed between a
      seven-stranded antiparallel beta-sheet and a C-terminal alpha-helix. Previously,
      some PR-10 proteins not related to nodulation were found to bind cytokinins such
      as trans-zeatin. Here, four crystal structures of the MtN13 protein are reported
      in complexes with several cytokinins, namely trans-zeatin, N6-isopentenyladenine,
      kinetin and N6-benzyladenine. All four phytohormones are bound in the hydrophobic
      cavity in the same manner and have excellent definition in the electron-density
      maps. The binding of the cytokinins appears to be strong and specific and is
      reinforced by several hydrogen bonds. Although the binding stoichiometry is 1:1,
      the complex is actually dimeric, with a cytokinin molecule bound in each subunit.
      The ligand-binding site in each cavity is formed with the participation of a loop
      element from the other subunit, which plugs the only entrance to the cavity.
      Interestingly, a homodimer of MtN13 is also formed in solution, as confirmed by
      small-angle X-ray scattering (SAXS).

PMID- 24311579
TI  - Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme
      crystals based on EPR, optical absorption and X-ray diffraction studies.
AB  - Electron paramagnetic resonance (EPR) and online UV-visible absorption
      microspectrophotometry with X-ray crystallography have been used in a
      complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV
      visible spectroscopy showed that upon X-irradiation, disulfide radicalization
      appeared to saturate at an absorbed dose of approximately 0.5-0.8 MGy, in
      contrast to the saturating dose of ~0.2 MGy observed using EPR at much lower dose
      rates. The observations suggest that a multi-track model involving product
      formation owing to the interaction of two separate tracks is a valid model for
      radiation damage in protein crystals. The saturation levels are remarkably
      consistent given the widely different experimental parameters and the range of
      total absorbed doses studied. The results indicate that even at the lowest doses
      used for structural investigations disulfide bonds are already radicalized. Multi
      track considerations offer the first step in a comprehensive model of radiation
      damage that could potentially lead to a combined computational and experimental
      approach to identifying when damage is likely to be present, to quantitate it and
      to provide the ability to recover the native unperturbed structure. 

PMID- 24311580
TI  - LigSearch: a knowledge-based web server to identify likely ligands for a protein
      target.
AB  - Identifying which ligands might bind to a protein before crystallization trials
      could provide a significant saving in time and resources. LigSearch, a web server
      aimed at predicting ligands that might bind to and stabilize a given protein, has
      been developed. Using a protein sequence and/or structure, the system searches
      against a variety of databases, combining available knowledge, and provides a
      clustered and ranked output of possible ligands. LigSearch can be accessed at
      http://www.ebi.ac.uk/thornton-srv/databases/LigSearch. 

PMID- 24311581
TI  - Duplex-quadruplex motifs in a peculiar structural organization cooperatively
      contribute to thrombin binding of a DNA aptamer.
AB  - Potent second-generation thrombin aptamers adopt a duplex-quadruplex bimodular
      folding and recognize thrombin exosite II with very high affinity and
      specificity. A sound model of these oligonucleotides, either free or in complex
      with thrombin, is not yet available. Here, a structural study of one of these
      aptamers, HD22-27mer, is presented. The crystal structure of this aptamer in
      complex with thrombin displays a novel architecture in which the helical stem is
      enchained to a pseudo-G-quadruplex. The results also underline the role of the
      residues that join the duplex and quadruplex motifs and control their recruitment
      in thrombin binding. 

PMID- 24311582
TI  - Structural insights into the role of the Chl4-Iml3 complex in kinetochore
      assembly.
AB  - Human CENP-N and CENP-L have been reported to selectively recognize the CENP-A
      nucleosome and to contribute to recruiting other constitutive centromere
      associated network (CCAN) complexes involved in assembly of the inner
      kinetochore. As their homologues, Chl4 and Iml3 from budding yeast function in a
      similar way in de novo assembly of the kinetochore. A lack of biochemical and
      structural information precludes further understanding of their exact role at the
      molecular level. Here, the crystal structure of Iml3 is presented and the
      structure shows that Iml3 adopts an elongated conformation with a series of
      intramolecular interactions. Pull-down assays revealed that the C-terminal domain
      of Chl4, which forms a dimer in solution, is responsible for Iml3 binding. Acting
      as a heterodimer, the Chl4-Iml3 complex exhibits a low-affinity nonspecific DNA
      binding activity which may play an important role in the kinetochore-assembly
      process. 

PMID- 24311583
TI  - The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with
      structural similarity to IFIT proteins.
AB  - TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-beta/TIR domain
      containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor
      (TLR) 3 and 4 signalling pathway that leads to the production of type 1
      interferons and cytokines. The signalling involves TIR (Toll/interleukin-1
      receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal
      region is believed to be involved in self-regulation of TRIF by interacting with
      its TIR domain. Here, the structural and functional characterization of the N
      terminal domain of TRIF (TRIF-NTD) comprising residues 1-153 is reported. The
      2.22 A resolution crystal structure was solved by single-wavelength anomalous
      diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing
      two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure
      consists of eight antiparallel helices that can be divided into two subdomains,
      and the overall fold shares similarity to the interferon-induced protein with
      tetratricopeptide repeats (IFIT) family of proteins, which are involved in both
      the recognition of viral RNA and modulation of innate immune signalling. Analysis
      of TRIF-NTD surface features and the mapping of sequence conservation onto the
      structure suggest several possible binding sites involved in either TRIF auto
      regulation or interaction with other signalling molecules or ligands. TRIF-NTD
      suppresses TRIF-mediated activation of the interferon-beta promoter, as well as
      NF-kappaB-dependent reporter-gene activity. These findings thus identify
      opportunities for the selective targeting of TLR3- and TLR4-mediated
      inflammation.

PMID- 24311585
TI  - Structural characterization of the ribonuclease H-like type ASKHA superfamily
      kinase MK0840 from Methanopyrus kandleri.
AB  - Murein recycling is a process in which microorganisms recover peptidoglycan
      degradation products in order to utilize them in cell wall biosynthesis or basic
      metabolic pathways. Methanogens such as Methanopyrus kandleri contain
      pseudomurein, which differs from bacterial murein in its composition and
      branching. Here, four crystal structures of the putative sugar kinase MK0840 from
      M. kandleri in apo and nucleotide-bound states are reported. MK0840 shows high
      similarity to bacterial anhydro-N-acetylmuramic acid kinase, which is involved in
      murein recycling. The structure shares a common fold with panthothenate kinase
      and the 2-hydroxyglutaryl-CoA dehydratase component A, both of which are members
      of the ASKHA (acetate and sugar kinases/Hsc70/actin) superfamily of
      phosphotransferases. Local conformational changes in the nucleotide-binding site
      between the apo and holo forms are observed upon nucleotide binding. Further
      insight is given into domain movements and putative active-site residues are
      identified. 

PMID- 24311584
TI  - Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2.
AB  - The histone H2A.Z variant is widely conserved among eukaryotes. Two isoforms,
      H2A.Z.1 and H2A.Z.2, have been identified in vertebrates and may have distinct
      functions in cell growth and gene expression. However, no structural differences
      between H2A.Z.1 and H2A.Z.2 have been reported. In the present study, the crystal
      structures of nucleosomes containing human H2A.Z.1 and H2A.Z.2 were determined.
      The structures of the L1 loop regions were found to clearly differ between
      H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are
      identical. This structural polymorphism may have been induced by a substitution
      that evolutionally occurred at the position of amino acid 38 and by the flexible
      nature of the L1 loops of H2A.Z.1 and H2A.Z.2. It was also found that in living
      cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2. A mutational
      analysis revealed that the amino-acid difference at position 38 is at least
      partially responsible for the distinctive dynamics of H2A.Z.1 and H2A.Z.2. These
      findings provide important new information for understanding the differences in
      the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells. 

PMID- 24311586
TI  - Protein design by fusion: implications for protein structure prediction and
      evolution.
AB  - Domain fusion is a useful tool in protein design. Here, the structure of a fusion
      of the heterodimeric flagella-assembly proteins FliS and FliC is reported.
      Although the ability of the fusion protein to maintain the structure of the
      heterodimer may be apparent, threading-based structural predictions do not
      properly fuse the heterodimer. Additional examples of naturally occurring
      heterodimers that are homologous to full-length proteins were identified. These
      examples highlight that the designed protein was engineered by the same tools as
      used in the natural evolution of proteins and that heterodimeric structures
      contain a wealth of information, currently unused, that can improve structural
      predictions. 

PMID- 24311587
TI  - Structures of native, substrate-bound and inhibited forms of Mycobacterium
      tuberculosis imidazoleglycerol-phosphate dehydratase.
AB  - Imidazoleglycerol-phosphate dehydratase (IGPD; HisB), which catalyses the
      conversion of imidazoleglycerol-phosphate (IGP) to imidazoleacetol-phosphate in
      the histidine biosynthesis pathway, is absent in mammals. This feature makes it
      an attractive target for herbicide discovery. Here, the crystal structure of
      Mycobacterium tuberculosis (Mtb) IGPD is reported together with the first crystal
      structures of substrate-bound and inhibited (by 3-amino-1,2,4-triazole; ATZ)
      forms of IGPD from any organism. The overall tertiary structure of Mtb IGPD, a
      four-helix-bundle sandwiched between two four-stranded mixed beta-sheets,
      resembles the three-dimensional structures of IPGD from other organisms; however,
      Mtb IGPD possesses a unique structural feature: the insertion of a one-turn 310
      helix followed by a loop ten residues in length. The functional form of IGPD is
      24-meric, exhibiting 432 point-group symmetry. The structure of the IGPD-IGP
      complex revealed that the imidazole ring of the IGP is firmly anchored between
      the two Mn atoms, that the rest of the substrate interacts through hydrogen bonds
      mainly with residues Glu21, Arg99, Glu180, Arg121 and Lys184 which protrude from
      three separate protomers and that the 24-mer assembly contains 24 catalytic
      centres. Both the structural and the kinetic data demonstrate that the inhibitor
      3-amino-1,2,4-triazole inhibits IGPD competitively. 

PMID- 24311588
TI  - Structural basis for type VI secreted peptidoglycan DL-endopeptidase function,
      specificity and neutralization in Serratia marcescens.
AB  - Some Gram-negative bacteria target their competitors by exploiting the type VI
      secretion system to extrude toxic effector proteins. To prevent self-harm, these
      bacteria also produce highly specific immunity proteins that neutralize these
      antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two
      type VI secretion-system-associated effectors from Serratia marcescens is
      characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between gamma
      D-glutamic acid and L-meso-diaminopimelic acid with different specificities. Ssp2
      degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays
      greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and
      pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the
      acceptor and donor strands. Functional assays confirm the identity of a catalytic
      cysteine in these endopeptidases and crystal structures provide information on
      the structure-activity relationships of Ssp1 and, by comparison, of related
      effectors. Functional assays also reveal that neutralization of these effectors
      by their cognate immunity proteins, which are called resistance-associated
      proteins (Raps), contributes an essential role to cell fitness. The structures of
      two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of
      Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds,
      with that of Rap1a not having previously been observed. The structure of the Ssp1
      Rap1a complex revealed a tightly bound heteromeric assembly with two effector
      molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1
      active site forms the basis of effector neutralization. Comparisons with Ssp2
      Rap2a orthologues suggest that the specificity of these immunity proteins for
      neutralizing effectors is fold-dependent and that in cases where the fold is
      conserved sequence differences contribute to the specificity of effector-immunity
      protein interactions. 

PMID- 24311589
TI  - High-resolution crystal structure of copper amine oxidase from Arthrobacter
      globiformis: assignment of bound diatomic molecules as O2.
AB  - The crystal structure of a copper amine oxidase from Arthrobacter globiformis was
      determined at 1.08 A resolution with the use of low-molecular-weight polyethylene
      glycol (LMW PEG; average molecular weight ~200) as a cryoprotectant. The final
      crystallographic R factor and Rfree were 13.0 and 15.0%, respectively. Several
      molecules of LMW PEG were found to occupy cavities in the protein interior,
      including the active site, which resulted in a marked reduction in the overall B
      factor and consequently led to a subatomic resolution structure for a relatively
      large protein with a monomer molecular weight of ~70,000. About 40% of the
      presumed H atoms were observed as clear electron densities in the Fo - Fc
      difference map. Multiple minor conformers were also identified for many residues.
      Anisotropic displacement fluctuations were evaluated in the active site, which
      contains a post-translationally derived quinone cofactor and a Cu atom.
      Furthermore, diatomic molecules, most likely to be molecular oxygen, are bound to
      the protein, one of which is located in a region that had previously been
      proposed as an entry route for the dioxygen substrate from the central cavity of
      the dimer interface to the active site.

PMID- 24311590
TI  - Phosphorylation adjacent to the nuclear localization signal of human dUTPase
      abolishes nuclear import: structural and mechanistic insights.
AB  - Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in
      the regulation of nucleocytoplasmic transport. The nuclear isoform of human
      dUTPase, an enzyme that is essential for genomic integrity, has been shown to be
      phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear
      localization signal; however, the effect of this phosphorylation is not yet
      known. To investigate this issue, an integrated set of structural, molecular and
      cell biological methods were employed. It is shown that NLS-adjacent
      phosphorylation of dUTPase occurs during the M phase of the cell cycle.
      Comparison of the cellular distribution of wild-type dUTPase with those of
      hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that
      phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus.
      Isothermal titration microcalorimetry and additional independent biophysical
      techniques show that the interaction between dUTPase and importin-alpha, the
      karyopherin molecule responsible for 'classical' NLS binding, is weakened
      significantly in the case of the S11E hyperphosphorylation-mimicking mutant. The
      structures of the importin-alpha-wild-type and the importin-alpha
      hyperphosphorylation-mimicking dUTPase NLS complexes provide structural insights
      into the molecular details of this regulation. The data indicate that the post
      translational modification of dUTPase during the cell cycle may modulate the
      nuclear availability of this enzyme. 

PMID- 24311591
TI  - Evidence for small-molecule-mediated loop stabilization in the structure of the
      isolated Pin1 WW domain.
AB  - The human Pin1 WW domain is a small autonomously folding protein that has been
      useful as a model system for biophysical studies of beta-sheet folding. This
      domain has resisted previous attempts at crystallization for X-ray diffraction
      studies, perhaps because of intrinsic conformational flexibility that interferes
      with the formation of a crystal lattice. Here, the crystal structure of the human
      Pin1 WW domain has been obtained via racemic crystallization in the presence of
      small-molecule additives. Both enantiomers of a 36-residue variant of the Pin1 WW
      domain were synthesized chemically, and the L- and D-polypeptides were combined
      to afford diffracting crystals. The structural data revealed packing interactions
      of small carboxylic acids, either achiral citrate or a D,L mixture of malic acid,
      with a mobile loop region of the WW-domain fold. These interactions with solution
      additives may explain our success in crystallization of this protein racemate.
      Molecular-dynamics simulations starting from the structure of the Pin1 WW domain
      suggest that the crystal structure closely resembles the conformation of this
      domain in solution. The structural data presented here should provide a basis for
      further studies of this important model system. 

PMID- 24311592
TI  - Split green fluorescent protein as a modular binding partner for protein
      crystallization.
AB  - A modular strategy for protein crystallization using split green fluorescent
      protein (GFP) as a crystallization partner is demonstrated. Insertion of a
      hairpin containing GFP beta-strands 10 and 11 into a surface loop of a target
      protein provides two chain crossings between the target and the reconstituted GFP
      compared with the single connection afforded by terminal GFP fusions. This
      strategy was tested by inserting this hairpin into a loop of another fluorescent
      protein, sfCherry. The crystal structure of the sfCherry-GFP(10-11) hairpin in
      complex with GFP(1-9) was determined at a resolution of 2.6 A. Analysis of the
      complex shows that the reconstituted GFP is attached to the target protein
      (sfCherry) in a structurally ordered way. This work opens the way to rapidly
      creating crystallization variants by reconstituting a target protein bearing the
      GFP(10-11) hairpin with a variety of GFP(1-9) mutants engineered for favorable
      crystallization. 

PMID- 24311593
TI  - Improvements in the order, isotropy and electron density of glypican-1 crystals
      by controlled dehydration.
AB  - The use of controlled dehydration for improvement of protein crystal diffraction
      quality is increasing in popularity, although there are still relatively few
      documented examples of success. A study has been carried out to establish whether
      controlled dehydration could be used to improve the anisotropy of crystals of the
      core protein of the human proteoglycan glypican-1. Crystals were subjected to
      controlled dehydration using the HC1 device. The optimal protocol for dehydration
      was developed by careful investigation of the following parameters: dehydration
      rate, final relative humidity and total incubation time Tinc. Of these, the most
      important was shown to be Tinc. After dehydration using the optimal protocol the
      crystals showed significantly reduced anisotropy and improved electron density,
      allowing the building of previously disordered parts of the structure. 

PMID- 24311594
TI  - Protein energy landscapes determined by five-dimensional crystallography.
AB  - Free-energy landscapes decisively determine the progress of enzymatically
      catalyzed reactions [Cornish-Bowden (2012), Fundamentals of Enzyme Kinetics, 4th
      ed.]. Time-resolved macromolecular crystallography unifies transient-state
      kinetics with structure determination [Moffat (2001), Chem. Rev. 101, 1569-1581;
      Schmidt et al. (2005), Methods Mol. Biol. 305, 115-154; Schmidt (2008),
      Ultrashort Laser Pulses in Medicine and Biology] because both can be determined
      from the same set of X-ray data. Here, it is demonstrated how barriers of
      activation can be determined solely from five-dimensional crystallography, where
      in addition to space and time, temperature is a variable as well [Schmidt et al.
      (2010), Acta Cryst. A66, 198-206]. Directly linking molecular structures with
      barriers of activation between them allows insight into the structural nature of
      the barrier to be gained. Comprehensive time series of crystallographic data at
      14 different temperature settings were analyzed and the entropy and enthalpy
      contributions to the barriers of activation were determined. One hundred years
      after the discovery of X-ray scattering, these results advance X-ray structure
      determination to a new frontier: the determination of energy landscapes. 

PMID- 24311595
TI  - The structure of Rv3717 reveals a novel amidase from Mycobacterium tuberculosis.
AB  - Bacterial N-acetylmuramoyl-L-alanine amidases are cell-wall hydrolases that
      hydrolyze the bond between N-acetylmuramic acid and L-alanine in cell-wall
      glycopeptides. Rv3717 of Mycobacterium tuberculosis has been identified as a
      unique autolysin that lacks a cell-wall-binding domain (CBD) and its structure
      has been determined to 1.7 A resolution by the Pt-SAD phasing method. Rv3717
      possesses an alpha/beta-fold and is a zinc-dependent hydrolase. The structure
      reveals a short flexible hairpin turn that partially occludes the active site and
      may be involved in autoregulation. This type of autoregulation of activity of PG
      hydrolases has been observed in Bartonella henselae amidase (AmiB) and may be a
      general mechanism used by some of the redundant amidases to regulate cell-wall
      hydrolase activity in bacteria. Rv3717 utilizes its net positive charge for
      substrate binding and exhibits activity towards a broad spectrum of substrate
      cell walls. The enzymatic activity of Rv3717 was confirmed by isolation and
      identification of its enzymatic products by LC/MS. These studies indicate that
      Rv3717, an N-acetylmuramoyl-L-alanine amidase from M. tuberculosis, represents a
      new family of lytic amidases that do not have a separate CBD and are regulated
      conformationally. 

PMID- 24311596
TI  - Structure of human apurinic/apyrimidinic endonuclease 1 with the essential Mg2+
      cofactor.
AB  - Apurinic/apyrimidinic endonuclease 1 (APE1) mediates the repair of abasic sites
      and other DNA lesions and is essential for base-excision repair and strand-break
      repair pathways. APE1 hydrolyzes the phosphodiester bond at abasic sites,
      producing 5'-deoxyribose phosphate and the 3'-OH primer needed for repair
      synthesis. It also has additional repair activities, including the removal of 3'
      blocking groups. APE1 is a powerful enzyme that absolutely requires Mg2+, but the
      stoichiometry and catalytic function of the divalent cation remain unresolved for
      APE1 and for other enzymes in the DNase I superfamily. Previously reported
      structures of DNA-free APE1 contained either Sm3+ or Pb2+ in the active site.
      However, these are poor surrogates for Mg2+ because Sm3+ is not a cofactor and
      Pb2+ inhibits APE1, and their coordination geometry is expected to differ from
      that of Mg2+. A crystal structure of human APE1 was solved at 1.92 A resolution
      with a single Mg2+ ion in the active site. The structure reveals ideal octahedral
      coordination of Mg2+ via two carboxylate groups and four water molecules. One
      residue that coordinates Mg2+ directly and two that bind inner-sphere water
      molecules are strictly conserved in the DNase I superfamily. This structure,
      together with a recent structure of the enzyme-product complex, inform on the
      stoichiometry and the role of Mg2+ in APE1-catalyzed reactions.

PMID- 24311598
TI  - Improving the soluble expression of recombinant proteins by randomly shuffling 5'
      and 3' coding-sequence ends.
AB  - Many structural genomics (SG) programmes rely on the design of soluble protein
      domains. The production and screening of large libraries to experimentally select
      these soluble protein-encoding constructs are limited by the technologies and
      efforts that can be devoted to a single target. Using basic technologies
      available in any laboratory, a method named 'boundary shuffling' was devised to
      generate orientated libraries for soluble domain selection without impeding the
      target flow. 

PMID- 24311597
TI  - Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation.
AB  - Hedgehog signalling plays a fundamental role in the control of metazoan
      development, cell proliferation and differentiation, as highlighted by the fact
      that its deregulation is associated with the development of many human tumours.
      SUFU is an essential intracellular negative regulator of mammalian Hedgehog
      signalling and acts by binding and modulating the activity of GLI transcription
      factors. Despite its central importance, little is known about SUFU regulation
      and the nature of SUFU-GLI interaction. Here, the crystal and small-angle X-ray
      scattering structures of full-length human SUFU and its complex with the key
      SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI
      binding is associated with major conformational changes in SUFU, including an
      intrinsically disordered loop that is also crucial for pathway activation. These
      findings reveal the structure of the SUFU-GLI interface and suggest a mechanism
      for an essential regulatory step in Hedgehog signalling, offering possibilities
      for the development of novel pathway modulators and therapeutics. 

PMID- 24311601
TI  - Clinical use of objective measures of physical activity.
AB  - With measurement of physical activity becoming more common in clinical practice,
      it is imperative that healthcare professionals become more knowledgeable about
      the different methods available to objectively measure physical activity
      behaviour. Objective measures do not rely on information provided by the patient,
      but instead measure and record the biomechanical or physiological consequences of
      performing physical activity, often in real time. As such, objective measures are
      not subject to the reporting bias or recall problems associated with self-report
      methods. The purpose of this article was to provide an overview of the different
      methods used to objectively measure physical activity in clinical practice. The
      review was delimited to heart rate monitoring, accelerometers and pedometers
      since their small size, low participant burden and relatively low cost make these
      objective measures appropriate for use in clinical practice settings. For each
      measure, strengths and weakness were discussed; and whenever possible, literature
      based examples of implementation were provided.

PMID- 24311602
TI  - Patellar taping for patellofemoral pain: a systematic review and meta-analysis to
      evaluate clinical outcomes and biomechanical mechanisms.
AB  - OBJECTIVE: Patellar taping is frequently used to treat patellofemoral pain (PFP).
      This systematic review and meta-analysis (1) evaluates the efficacy of patellar
      taping for patients with PFP, (2) compares the efficacy of various taping
      techniques and (3) identifies potential biomechanical mechanisms of action.
      METHODS: The MEDLINE, CINAHL, SPORTSDiscus, Web of Science and Google Scholar
      databases were searched in January 2013 for studies evaluating the effects of
      patellar taping on pain and lower-limb biomechanics in individuals with PFP.
      Three independent reviewers assessed each paper for inclusion and two assessed
      for quality. Means and SDs were extracted from each included study to allow
      effect size calculations. RESULTS: Twenty studies were identified. There is
      moderate evidence that (1) tailored (customised to the patient to control lateral
      tilt, glide and spin) and untailored patellar taping provides immediate pain
      reduction of large and small effect, respectively and (2) tailored patellar
      taping promotes earlier onset of vastus medialis oblique (VMO) contraction
      (relative to vastus lateralis contraction). There is limited evidence that (1)
      tailored patellar taping combined with exercise provides superior pain reduction
      compared to exercise alone at 4 weeks, (2) untailored patellar taping added to
      exercise at 3-12 months has no benefit and (3) tailored patellar taping promotes
      increased internal knee extension moments. CONCLUSIONS: Tailoring patellar taping
      application (ie, to control lateral tilt, glide and spin) to optimise pain
      reduction is important for efficacy. Evaluation of tailored patellar taping
      beyond the immediate term is limited and should be a research priority. Possible
      mechanisms behind patellar taping efficacy include earlier VMO onset and improved
      knee function capacity (ie, ability to tolerate greater internal knee extension
      moments).

PMID- 24311603
TI  - Incorporating 'Exercise is Medicine' into the University of South Carolina School
      of Medicine Greenville and Greenville Health System.

PMID- 24311605
TI  - Chimp acupuncture.

PMID- 24311608
TI  - Clinician's view.

PMID- 24311609
TI  - Circulation Research launches a clinical track for studies in humans.

PMID- 24311610
TI  - Cyclophilin D and acetylation: a new link in cardiac signaling.

PMID- 24311611
TI  - MicroRNA-223 made its way into vascular research.

PMID- 24311612
TI  - Thrombospondin-1: the good, the bad, and the complicated.

PMID- 24311613
TI  - High-density lipoprotein: NO failure in heart failure.

PMID- 24311614
TI  - Remote ischemic preconditioning: no loss in clinical translation.

PMID- 24311615
TI  - Protection against ischemia/reperfusion injury by high-density lipoprotein and
      its components.

PMID- 24311616
TI  - Diverse contributions from the initial discovery of mechanisms of angiotensin II
      induced oxidation in smooth muscle cells.

PMID- 24311617
TI  - 2013 Lucian Award: David Ginsburg.

PMID- 24311619
TI  - Recent advances in the role of immunity in atherosclerosis.

PMID- 24311618
TI  - Recent advances in mitochondrial research.

PMID- 24311620
TI  - Noncoding RNAs in cardiovascular biology and disease.

PMID- 24311621
TI  - Recent advances in cardiac myocyte biology and function.

PMID- 24311623
TI  - Irreversible thyroid disruption induced after subchronic exposure to
      hexachlorobenzene in male rats.
AB  - Thyroid hormones play a complex role in the toxicity of hexachlorobenzene (HCB)
      and related compounds. Time-course and dose-response experiments for free- and
      total thyroxine (T4) and triiodothyronine (T3) plasma levels for thyroid
      stimulating hormone (TSH) and thyroid gland histomorphology were determined in
      male Wistar rats. Also, we examined the possible reversibility of changes noted
      after removal of HCB. Rats treated with this organochlorine compound resulted in
      a hypertrophy of the thyroid gland and altered thyroid function by decreasing
      significantly the levels of total- and free T4 in a dose-dependent manner (total
      T4: 28 and 51%; free T4: 21 and 37%), and this decrease was seen as early as 21
      days and thereafter. Free T3 was also decreased by 21% with the highest dose
      starting from day 21. No significant changes were observed in the circulating
      levels of total T3 In response to the decrease of thyroid hormones, a dose
      dependent increase of TSH levels (27 and 31%, respectively, for 4 mg and 16 mg/kg
      of HCB body weight) was observed after 21 days of HCB treatment. We have observed
      a hypertrophy and hyperplasia of follicular cells and a decrease in colloid
      volume in histological picture. When HCB was removed and changed by vehicle, the
      thyroid relative weight and plasma TSH continued to rise and serum thyroid
      hormones remained suppressed. These findings suggest that subchronic exposure of
      rats to HCB induced an irreversible hypothyroidism state. 

PMID- 24311624
TI  - A probable role of blood lead levels on some haematological parameters in traffic
      police, Lahore, Pakistan.
AB  - The impact of elevated blood lead level on some haematological parameters was
      studied in the field force of Lahore traffic police, in Pakistan. The blood
      samples were tested for total leucocytes count (TLC) and differential leucocytes
      count in the persons with high and low blood lead levels. The TLC and percentage
      of neutrophils and eosinophils were observed as being significantly elevated in
      the policemen. No significant change was observed in the percentage of
      lymphocytes, while the percentage of monocytes was observed as being
      significantly less in the field force of traffic police. 

PMID- 24311625
TI  - Chemotherapy-induced acral erythema with involvement of the face and neck: A case
      report.
AB  - Chemotherapy-induced acral erythema (CIAE) is a cutaneous response to diverse
      chemotherapeutic drug administration. These drugs cause symmetrical and painful
      erythema of palmoplantar surfaces. Bulla formation, desquamation, and subsequent
      reepithelialization may occur. Commonly, the lesions slowly resolve over 7-15
      days, through desquamation, followed by regeneration of the skin. Here, we
      described a case of CIAE, with involvement of face and neck in a patient treated
      for breast cancer using a number of chemotherapeutic agents. Face involvement in
      CIAE has not been previously reported in the literature. 

PMID- 24311626
TI  - Dose-dependent genotoxicity of copper oxide nanoparticles stimulated by reactive
      oxygen species in human lung epithelial cells.
AB  - Copper oxide nanoparticles (CuO NPs) are of great interest in nanoscience and
      nanotechnology because of their broad industrial and commercial applications.
      Therefore, toxicity of CuO NPs needs to be thoroughly understood. The aim of this
      study was to investigate the cytotoxicity, genotoxicity, and oxidative stress
      induced by CuO NPs in human lung epithelial (A549) cells. CuO NPs were
      synthesized by solvothermal method and the size of NPs measured under
      transmission electron microscopy (TEM) was found to be around 23 nm. The 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and lactate
      dehydrogenase (LDH) assays showed that CuO NPs (5-15 ug/ml) exert cytotoxicity in
      A549 cells in a dose-dependent manner. Comet assay suggested concentration
      dependent induction of DNA damage due to the exposure to CuO NPs. The comet tail
      moment was 27% at 15 ug/ml of CuO NPs, whereas it was 5% in control (p < 0.05).
      The flow cytometry data revealed that CuO NPs induced micronuclei (MN) in A549
      cells dose dependently. The frequency of MN was 25/10(3) cells at 15 ug/ml of CuO
      NPs, whereas it was 2/10(3) cells for control. CuO NPs were also found to induce
      oxidative stress in a concentration-dependent manner, which was indicated by
      induction of reactive oxygen species (ROS) and lipid peroxidation along with
      glutathione depletion. Moreover, MN induction and DNA damage were significantly
      correlated with ROS (R(2) = 0.937 for ROS vs. olive tail moment, and R(2) = 0.944
      for ROS vs. MN). Taken together, this study suggested that CuO NPs induce
      genotoxicity in A549 cells, which is likely to be mediated through ROS generation
      and oxidative stress. 

PMID- 24311627
TI  - Neuroprotective effects of folic acid on experimental diabetic peripheral
      neuropathy.
AB  - Diabetic peripheral neuropathy (DPN) is widely considered as a degenerative
      complication of diabetic patients. The clinical effectiveness of folic acid (FA)
      on DPN is uncertain. The objective of the present study was to determine the
      effect of FA in DPN using electromyography (EMG), histopathological examination,
      immunohistochemistry, inclined plane test, and malondialdehyde (MDA) levels as a
      marker for lipid peroxidation in experimental diabetic rats. A total of 21
      Sprague Dawley rats were randomly divided into 3 groups: control group, diabetes
      group, and FA-treated group. In EMG, compound muscle action potential (CMAP)
      amplitude in the sciatic nerve was lower in the diabetes group compared with the
      control group. CMAP amplitude in the sciatic nerve was higher in the FA-treated
      group when compared with the diabetes group. Distal latency and CMAP duration in
      the sciatic nerve were lower in the FA-treated group when compared with the
      diabetes group. In histopathological examination of the sciatic nerve, peripheral
      fibrosis was present in the diabetic group; the fibrosis was lower in the FA
      treated group. In comparison with the diabetes group, the expression of nerve
      growth factor (NGF) was higher in the FA-treated group. The scores for the
      inclined plane test were lower in the diabetes group and higher in the FA-treated
      group than the control group. The MDA levels were significantly lower in the FA
      treated group when compared with the diabetes group.The study suggests that FA
      can protect diabetic rats against DPN and that the underlying mechanism for this
      may be related to improvement of the expression of NGF and lower MDA levels. 

PMID- 24311628
TI  - Phytochemical analysis, antibacterial, and antifungal assessment of aerial parts
      of Polygonatum verticillatum.
AB  - The current study was designed to assess the phytochemical profile,
      antibacterial, and antifungal activities of the crude methanol extract of the
      aerial parts of Polygonatum verticillatum (PA) and its various subsequent solvent
      fractions using agar well diffusion, agar tube dilution, and microdilution
      methods. Phytochemical analysis showed positive for different chemical groups and
      also contained marked quantity of saponin and flavonoid contents. Significant
      antibacterial activity was observed against various tested pathogenic bacteria.
      The only susceptible Gram-positive bacterium was Bacillus subtilis and their
      minimum inhibitory concentrations (MICs) measured ranged from 11-50 ug/ml. The
      sensitive Gram-negative bacteria were Salmonella typhi and Shigella flexeneri The
      estimated MICs were in the range of 2-7 ug/ml and 8-50 ug/ml for S. typhi and S.
      flexeneri, respectively. However, the antifungal activity of the plant was
      limited to Microsporum canis and their MICs ranged from 60 to 250 ug/ml. Our
      study confirmed significant antibacterial potential of the plant and
      substantiated its folk use in dysentery and pyrexia of multiple origins. 

PMID- 24311629
TI  - Changes of c-Myc and DNMT1 mRNA and protein levels in the rat livers induced by
      dibutyl phthalate treatment.
AB  - We investigated the relationship between dibutyl phthalate (DBP)-induced
      hypomethylation of the c-Myc promoter region (as evident in our early study) and
      the expression of c-Myc and DNMT1 genes (at messenger RNA (mRNA) and protein
      level) in the rat liver. Male Wistar rats received DBP in 1, 3, or 14 daily doses
      of 1800 mg kg(-1) body weight. Levels of DNMT1, c-Myc mRNA, and proteins were
      detected using real-time polymerase chain reaction and Western blot analysis,
      respectively. Our findings indicate that DBP caused an increase in mRNA levels of
      c-Myc at all time points. The results showed that protein levels of c-Myc in rat
      liver also increased significantly by DBP treatment, which were more pronounced
      at last time point (after 14 doses). Furthermore, overexpression of DNMT1gene
      have been found after one dose of DBP, which was confirmed at the protein level
      by Western blot analysis. Reduced levels of DNMT1mRNA and proteins (3 and 14
      doses) were coordinated with depletion DNA synthesis (reported previously). Based
      on our previous results and those presented here, the following conclusion could
      be drawn: (1) DBP exerted biological activity through epigenetic modulation of c
      Myc gene expression; (2) it seems possible that DBP-induced active demethylation
      of c-Myc gene through mechanism(s) linked to generation of reactive oxygen
      species by activated c-Myc; and (3) control of DNA replication was not directly
      dependent on c-Myc transcriptional activity and we attribute this finding to
      DNMT1gene expression which was tightly coordinated with DNA synthesis. 

PMID- 24311631
TI  - Sequencing IDH1/2 glioma mutation hotspots in gliomas and malignant peripheral
      nerve sheath tumors.

PMID- 24311630
TI  - NSAIDs inhibit tumorigenesis, but how?
AB  - Numerous epidemiologic studies have reported that the long-term use of
      nonsteroidal anti-inflammatory drugs (NSAID) is associated with a significant
      decrease in cancer incidence and delayed progression of malignant disease. The
      use of NSAIDs has also been linked with reduced risk from cancer-related
      mortality and distant metastasis. Certain prescription-strength NSAIDs, such as
      sulindac, have been shown to cause regression of precancerous lesions.
      Unfortunately, the extended use of NSAIDs for chemoprevention results in
      potentially fatal side effects related to their COX-inhibitory activity and
      suppression of prostaglandin synthesis. Although the basis for the tumor growth
      inhibitory activity of NSAIDs likely involves multiple effects on tumor cells and
      their microenvironment, numerous investigators have concluded that the underlying
      mechanism is not completely explained by COX inhibition. It may therefore be
      possible to develop safer and more efficacious drugs by targeting such COX
      independent mechanisms. NSAID derivatives or metabolites that lack COX-inhibitory
      activity, but retain or have improved anticancer activity, support this
      possibility. Experimental studies suggest that apoptosis induction and
      suppression of beta-catenin-dependent transcription are important aspects of
      their antineoplastic activity. Studies show that the latter involves
      phosphodiesterase inhibition and the elevation of intracellular cyclic GMP
      levels. Here, we review the evidence for COX-independent mechanisms and discuss
      progress toward identifying alternative targets and developing NSAID derivatives
      that lack COX-inhibitory activity but have improved antineoplastic properties.

PMID- 24311632
TI  - Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade
      gliomas--a Pediatric Brain Tumor Consortium study.
AB  - BACKGROUND: A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was
      conducted in children with recurrent low-grade glioma to measure sustained
      response and/or stable disease lasting >=6 months and progression-free survival.
      METHODS: Thirty-five evaluable patients received 2 doses (10 mg/kg each) of
      single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks
      until progressive disease, unacceptable toxicity, or a maximum of 2 years of
      therapy. Correlative studies included neuroimaging and expression of tumor
      angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2,
      hypoxia-inducible factor 2alpha, and carbonic anhydrase 9). RESULTS: Thirty-five
      evaluable patients (median age 8.4 y [range, 0.6-17.6]) received a median of 12
      courses of BVZ + CPT-11 (range, 2-26). Twenty-nine of 35 patients (83%) received
      treatment for at least 6 months. Eight patients progressed on treatment at a
      median time of 5.4 months (range, 1-17.8). Six patients (17.7%) still in follow
      up have had stable disease without receiving additional treatment for a median of
      40.1 months (range, 30.6-49.3) from initiating therapy. The 6-month and 2-year
      progression-free survivals were 85.4% (SE +/- 5.96%) and 47.8% (SE +/- 9.27%),
      respectively. The commonest toxicities related to BVZ included grades 1-2
      hypertension in 24, grades 1-2 fatigue in 23, grades 1-2 epistaxis in 18, and
      grades 1-4 proteinuria in 15. The median volume of enhancement decreased
      significantly between baseline and day 15 (P < .0001) and over the duration of
      treatment (P < .037). CONCLUSION: The combination of BVZ + CPT-11 appears to
      produce sustained disease control in some children with recurrent low-grade
      gliomas.

PMID- 24311633
TI  - A novel C19MC amplified cell line links Lin28/let-7 to mTOR signaling in
      embryonal tumor with multilayered rosettes.
AB  - BACKGROUND: Embryonal tumor with multilayered rosettes (ETMR) is an aggressive
      central nervous system primitive neuroectodermal tumor (CNS-PNET) variant. ETMRs
      have distinctive histology, amplification of the chromosome 19 microRNA cluster
      (C19MC) at chr19q13.41-42, expression of the RNA binding protein Lin28, and
      dismal prognosis. Functional and therapeutic studies of ETMR have been limited by
      a lack of model systems. METHODS: We have established a first cell line, BT183,
      from a case of ETMR and characterized its molecular and cellular features. LIN28
      knockdown was performed in BT183 to examine the potential role of Lin28 in
      regulating signaling pathway gene expression in ETMR. Cell line findings were
      corroborated with immunohistochemical studies in ETMR tissues. A drug screen of
      73 compounds was performed to identify potential therapeutic targets. RESULTS:
      The BT183 line maintains C19MC amplification, expresses C19MC-encoded microRNAs,
      and is tumor initiating. ETMRs, including BT183, have high LIN28 expression and
      low let-7 miRNA expression, and show evidence of mTOR pathway activation. LIN28
      knockdown increases let-7 expression and decreases expression of IGF/PI3K/mTOR
      pathway components. Pharmacologic inhibition of the mTOR pathway reduces BT183
      cell viability. CONCLUSIONS: BT183 retains key genetic and histologic features of
      ETMR. In ETMR, Lin28 is not only a diagnostic marker but also a regulator of
      genes involved in growth and metabolism. Our findings indicate that inhibitors of
      the IGF/PI3K/mTOR pathway may be promising novel therapies for these fatal
      embryonal tumors. As the first patient-derived cell line of these rare tumors,
      BT183 is an important, unique reagent for investigating ETMR biology and
      therapeutics.

PMID- 24311634
TI  - BRAF-V600E mutation in pediatric and adult glioblastoma.

PMID- 24311635
TI  - The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma
      stem-like cells.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) has been suggested as a
      target for radiosensitization. Given that radiotherapy is a primary treatment
      modality for glioblastoma (GBM) and that mTOR is often dysregulated in GBM, the
      goal of this study was to determine the effects of AZD2014, a dual mTORC1/2
      inhibitor, on the radiosensitivity of GBM stem-like cells (GSCs). METHODS: mTORC1
      and mTORC2 activities were defined by immunoblot analysis. The effects of this
      mTOR inhibitor on the in vitro radiosensitivity of GSCs were determined using a
      clonogenic assay. DNA double strand breaks were evaluated according to gammaH2AX
      foci. Orthotopic xenografts initiated from GSCs were used to define the in vivo
      response to AZD2014 and radiation. RESULTS: Exposure of GSCs to AZD2014 resulted
      in the inhibition of mTORC1 and 2 activities. Based on clonogenic survival
      analysis, addition of AZD2014 to culture media 1 hour before irradiation enhanced
      the radiosensitivity of CD133+ and CD15+ GSC cell lines. Whereas AZD2014
      treatment had no effect on the initial level of gammaH2AX foci, the dispersal of
      radiation-induced gammaH2AX foci was significantly delayed. Finally, the
      combination of AZD2014 and radiation delivered to mice bearing GSC-initiated
      orthotopic xenografts significantly prolonged survival as compared with the
      individual treatments. CONCLUSIONS: These data indicate that AZD2014 enhances the
      radiosensitivity of GSCs both in vitro and under orthotopic in vivo conditions
      and suggest that this effect involves an inhibition of DNA repair. Moreover,
      these results suggest that this dual mTORC1/2 inhibitor may be a radiosensitizer
      applicable to GBM therapy.

PMID- 24311636
TI  - Response of primary glioblastoma cells to therapy is patient specific and
      independent of cancer stem cell phenotype.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) contains a population of cells that
      exhibit stem cell phenotypes. These cancer stem cells (CSCs) may be a source of
      therapeutic resistance, although support for this important concept is limited.
      METHODS: We determined whether early-passage GBM CSCs respond differently than
      patient-matched, genotypically similar non-CSCs to clinically relevant single or
      serial doses of temozolomide (TMZ), radiation therapy (XRT), or alternating TMZ
      treatment and XRT, which is the standard of care for GBM patients. RESULTS:
      Despite the phenotypic differences, including the presence of stem cell markers
      and formation of intracranial tumors, the CSCs and matched non-CSCs were equally
      resistant to TMZ in a majority of patients, using 2 independent assays. TMZ
      response was consistent with methylated O(6)-DNA methylguanine-methyltransferase
      (MGMT) and MGMT protein levels in both culture types. In contrast, CSCs were
      unexpectedly more responsive to XRT compared with matched non-CSCs from 2
      patients despite having relatively equal resistance to TMZ. However, for the
      majority of culture pairs from individual patients, responses in CSCs were
      indistinguishable from non-CSC cultures. CONCLUSIONS: In our patient-matched
      primary cultures, response to TMZ was tightly linked to the individual tumor's
      MGMT status and independent of their phenotypic differences. TMZ and XRT together
      revealed no additive benefit compared with monotherapy for either culture type,
      in contrast to the notion that the CSC population is more resistant to XRT. If
      the tumor cell response in vitro mirrors therapeutic response in larger patient
      cohorts, these rapid assays in primary cultures could allow -empirical selection
      of efficacious therapeutic agents on a patient-specific basis.

PMID- 24311637
TI  - A single-arm phase II Austrian/German multicenter trial on continuous daily
      sunitinib in primary glioblastoma at first recurrence (SURGE 01-07).
AB  - BACKGROUND: Due to the redundancy of molecular pathways simultaneously involved
      in glioblastoma growth and angiogenesis, therapeutic approaches intervening at
      multiple levels seem particularly appealing. METHODS: This prospective,
      multicenter, single-arm phase II trial was designed to evaluate the antitumor
      activity of sunitinib, an oral small-molecule inhibitor of several receptor
      tyrosine kinases, in patients with first recurrence of primary glioblastoma using
      a continuous once-daily dosing regimen. Patients received a starting dose of
      sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg
      depending on drug tolerability. The primary endpoint was a 6-month progression
      free survival (PFS) rate. Secondary endpoints included median PFS, overall
      survival (OS), safety/toxicity, quality of life, and translational studies on the
      expression of sunitinib target molecules. RESULTS: Forty participants were
      included in this study, and no objective responses were detected. PFS6 was 12.5%,
      median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed
      prolonged stable disease >=6 months with a median PFS of 16.0 months (range, 6.4
      41.4 mo) and a median OS of 46.9 months (range, 21.2-49.2 mo) for this subgroup.
      c-KIT expression in vascular endothelial cells (n = 14 participants) was
      associated with improved PFS. The most common toxicities were fatigue/asthenia,
      mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive
      impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated
      treatment due to toxicity. CONCLUSION: Continuous daily sunitinib showed minimal
      antiglioblastoma activity and substantial toxicity when given at higher doses.
      High endothelial c-KIT expression may define a subgroup of patients who will
      benefit from sunitinib treatment by achieving prolonged PFS. ClinicalTrials.gov
      Identifier: NCT00535379.

PMID- 24311638
TI  - Technique, outcomes, and acute toxicities in adults treated with proton beam
      craniospinal irradiation.
AB  - BACKGROUND: Proton craniospinal irradiation (p-CSI) has been proposed to reduce
      side effects associated with CSI. We evaluated acute toxicities and preliminary
      clinical outcomes in a series of adults treated with p-CSI. METHODS: We reviewed
      medical records for 50 patients (aged 16-63 y) with malignancies of varying
      histologies treated consecutively with vertebral body-sparing p-CSI at MD
      Anderson Cancer Center from 2007 to 2011. Median CSI and total boost doses were
      30.6 and 54 Gy. Forty patients received chemotherapy, varying by histology.
      Median follow-up was 20.1 months (range, 0.3-59). RESULTS: Median doses to the
      thyroid gland, pituitary gland, hypothalamus, and cochleae were 0.003 Gy-relative
      biological effectiveness (RBE; range, 0.001-8.5), 36.1 Gy-RBE (22.5-53.0), 37.1
      Gy-RBE (22.3-54.4), and 33.9 Gy-RBE (22.2-52.4), respectively. Median percent
      weight loss during CSI was 1.6% (range, 10% weight loss to 14% weight gain). Mild
      nausea/vomiting was common (grade 1 = 46%, grade 2 = 20%); however, only 5
      patients experienced grade >=2 anorexia (weight loss >5% baseline weight). Median
      percent baseline white blood cells, hemoglobin, and platelets at nadir were 52%
      (range, 13%-100%), 97% (65%-112%), and 61% (10%-270%), respectively. Four
      patients developed grade >=3 cytopenias. Overall and progression-free survival
      rates were 96% and 82%, respectively, at 2 years and 84% and 68% at 5 years.
      CONCLUSIONS: This large series of patients treated with p-CSI confirms low rates
      of acute toxicity, consistent with dosimetric models. Vertebral body-sparing p
      CSI is feasible and should be considered as a way to reduce acute
      gastrointestinal and hematologic toxicity in adults requiring CSI.

PMID- 24311639
TI  - Functional role of endothelial adhesion molecules in the early stages of brain
      metastasis.
AB  - BACKGROUND: Cellular adhesion molecules (CAMs), which are normally associated
      with leukocyte trafficking, have also been shown to play an essential role in
      tumor metastasis to non-CNS sites. However, the role played by CAMs in brain
      metastasis is largely unexplored. It is known that leukocyte recruitment to the
      brain is very atypical and that mechanisms of disease in peripheral tissues
      cannot be extrapolated to the brain. Here, we have established the spatiotemporal
      expression of 12 key CAMs in the initial phases of tumor seeding in 2 different
      models of brain metastasis. METHODS: BALB/c or SCID mice were injected
      intracardially (10(5) cells/100 MUL phosphate-buffered saline with either 4T1-GFP
      or MDA231BR-GFP cells, respectively (n = 4-6/group), and expression of the CAMs
      was determined by immunohistochemistry and immunofluorescence colocalisation.
      RESULTS: Endothelial expression of E-selectin, VCAM-1, ALCAM, ICAM-1, VLA-4, and
      beta4 integrin was markedly increased early in tumor seeding. At the same time,
      the natural ligands to these adhesion molecules were highly expressed on the
      metastatic tumor cells both in vitro and in vivo. Two of these ligands showed
      particularly high tumor cell expression (ALCAM and VLA-4), and consequently their
      functional role in tumor seeding was determined. Antibody neutralization of
      either ALCAM or VLA-4 significantly reduced tumor seeding within the brain (>60%
      decrease in tumor number/mm(2) brain; P < .05-0.01). CONCLUSIONS: These findings
      suggest that ALCAM/ALCAM and VLA-4/VCAM-1 interactions play an important
      functional role in the early stages of metastasis seeding in the brain. Moreover,
      this work identifies a specific subset of ligand-receptor interactions that may
      yield new therapeutic and diagnostic targets for brain metastasis.

PMID- 24311640
TI  - Assessment of prognostic scores in brain metastases from breast cancer.
AB  - BACKGROUND: Breast cancer (BC) is the second most common cause of brain
      metastases (BM). Optimal management of BM from BC is still debated. In an attempt
      to provide appropriate treatment and to assist with optimal patient selection,
      several specific prognostic classifications for BM from BC have been established.
      We evaluated the prognostic value and validity of the 6 proposed scoring systems
      in an independent population of BC patients with BM. METHODS: We retrospectively
      reviewed all consecutive BC patients referred to our institution for newly
      diagnosed BM between October 1995 and July 2011 (n = 149). Each of the 6 scores
      proposed for BM from BC (Sperduto, Niwinska, Park, Nieder, Le Scodan, and Claude)
      was applied to this population. The discriminative ability of each score was
      assessed using the Brier score and the C-index. Individual prognostic values of
      clinical and histological factors were analyzed using uni- and multivariate
      analyses. RESULTS: Median overall survival was 15.1 months (95% CI,11.5-18.7).
      Sperduto-GPA (P < .001), Nieder (P < .001), Park (P < .001), Claude (P < .001),
      Niwinska (P < .001), and Le Scodan (P = .034) scores all showed significant
      prognostic value. The Nieder score showed the best discriminative ability (C
      index, 0.672; Brier score error reduction, 16.1%). CONCLUSION: The majority of
      prognostic scores were relevant for patients with BM from BC in our independent
      population, and the Nieder score seems to present the best predictive value but
      showed a relatively low positive predictive value. Thus, these results remain
      insufficient and challenge the routine use of these scoring systems.

PMID- 24311642
TI  - The legend of cytomegalovirus and glioblastoma lives on.

PMID- 24311641
TI  - Loss of heterozygosity 1p/19q and survival in glioma: a meta-analysis.
AB  - BACKGROUND: Glioma is rarely curable, and factors that influence the prognosis of
      glioma patients are not fully understood. Loss of heterozygosity (LOH) of 1p/19q
      has long been known to be a typical molecular signature of oligodendroglial
      neoplasms. However, whether LOH of 1p/19q is associated with survival in gliomas
      remains controversial. Here our goal was to evaluate the association between LOH
      of 1p/19q and progression-free survival (PFS) and overall survival (OS) by
      conducting a meta-analysis among glioma cases. METHODS: The PubMed and Embase
      databases were searched from the earliest records to May 2013 to identify studies
      that met prestated inclusion criteria. Reference lists of retrieved articles were
      also reviewed. Three authors independently extracted information needed for
      further analysis. Either a fixed- or a random-effects model was used to calculate
      the overall combined hazard ratio (HR) estimates. RESULTS: Twenty-eight eligible
      studies involving 3 408 cases were included in the meta-analysis. Compared with
      the chromosomal intact group, codeletion of 1p and 19q was associated with a
      better PFS (HR = 0.63; 95% CI, 0.52-0.76) and OS (HR = 0.43; 95% CI, 0.35-0.53).
      Subgroup analyses showed this association to be independent of detection methods
      and the grades and subtypes of gliomas. Furthermore, isodeletion of chromosome 1p
      predicted a similar favorable disease outcome (PFS: HR = 0.68; 95% CI, 0.47-0.97)
      (OS: HR = 0.51; 95% CI, 0.35-0.75), especially in low-grade gliomas, whereas
      isodeletion of 19q only indicated longer PFS (HR = 0.70; 95% CI, 0.56-0.87).
      CONCLUSION: Codeletion of 1p and 19q is associated with better survival rates in
      glioma. Isodeletion of 1p predicts similar outcomes but to a lesser extent,
      whereas the effects of isodeletion of 19q remained only marginal.

PMID- 24311643
TI  - Phase II study of everolimus in children and adults with neurofibromatosis type 2
      and progressive vestibular schwannomas.
AB  - BACKGROUND: Activation of the mammalian target of rapamycin (mTOR) signaling
      pathway is thought to be a key driver of tumor growth in Merlin (NF2)-deficient
      tumors. Everolimus is an oral inhibitor of mTOR complex 1 (mTORC1) with antitumor
      activity in a variety of cancers. METHODS: We conducted a single-institution,
      prospective, 2-stage, open-label phase II study to estimate the response rate to
      everolimus in neurofibromatosis type 2 (NF2) patients with progressive vestibular
      schwannoma (VS). Ten eligible patients were enrolled, including 2 pediatric
      patients. Everolimus was administered at a daily dose of 10 mg (adults) or 5
      mg/m(2)/day (children <18 y) orally in continuous 28-day courses, for up to 12
      courses. Response was assessed every 3 months with MRI, using 3-dimensional
      volumetric tumor analysis, and audiograms. Nine patients were evaluable for the
      primary response, defined as >=15% decrease in VS volume. Hearing response was
      evaluable as a secondary endpoint in 8 patients. RESULTS: None of the 9 patients
      with evaluable disease experienced a clinical or MRI response. No objective
      imaging or hearing responses were observed in stage 1 of the trial, and the study
      was closed according to predefined stopping rules. CONCLUSION: Everolimus is
      ineffective for the treatment of progressive VS in NF2 patients. We are currently
      conducting a pharmacokinetic/pharmacodynamic ("phase 0") study of everolimus in
      presurgical VS patients to elucidate the biological basis for apparent treatment
      resistance to mTORC1 inhibition in these tumors.

PMID- 24311644
TI  - Levetiracetam and pregabalin for antiepileptic monotherapy in patients with
      primary brain tumors. A phase II randomized study.
AB  - BACKGROUND: In patients with brain tumors, the choice of antiepileptic medication
      is guided by tolerability and pharmacokinetic interactions. This study
      investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non
      enzyme-inducing agents, in this setting. METHODS: In this pragmatic, randomized,
      unblinded phase II trial (NCT00629889), patients with primary brain tumors and
      epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability
      were assessed using structured questionnaires. The primary composite endpoint was
      the need to discontinue the study drug, add-on of a further antiepileptic
      treatment, or occurrence of at least 2 seizures with impaired consciousness
      during 1 year follow-up. RESULTS: Over 40 months, 25 patients were randomized to
      LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at
      least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg
      (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The
      composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue:
      side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral
      administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures
      impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor
      progression. CONCLUSIONS: This study shows that LEV and PGB represent valuable
      monotherapy options in this setting, with very good antiepileptic efficacy and an
      acceptable tolerability profile, and provides important data for the design of a
      phase III trial.

PMID- 24311645
TI  - TCTP promotes glioma cell proliferation in vitro and in vivo via enhanced beta
      catenin/TCF-4 transcription.
AB  - Background The translationally controlled tumor protein (TCTP) is a
      multifunctional protein that plays important roles in immune responses, cell
      proliferation, tumorigenicity and cell apoptosis. Here, we examined the clinical
      value of TCTP in glioma patient survival and investigated the functional roles
      and mechanism of TCTP in glioma development. Methods TCTP expression was
      determined through immunohistochemical staining, immunoblotting, and quantitative
      real-time PCR (qRT-PCR). TCTP or TCF-4 expression was silenced using short
      hairpin (sh) RNA. In vitro cell proliferation was detected using MTT, BrdU and
      colony formation assays, and in vivo tumor growth was performed using the
      xenograft model. TCTP/TCF-4/beta-catenin association was detected using a co
      immunoprecipitation (co-IP) assay. TCF-4 transcription activity was detected
      using a TOPflash/FOPflash report gene assay. Wnt/beta-catenin-targeted gene
      expression was detected through Western blotting. Results TCTP protein levels
      were significantly elevated in high-grade gliomas compared with low-grade gliomas
      and normal brain tissues. Importantly, the expression of TCTP was significantly
      associated with poorer overall survival and disease-free survival, and TCTP also
      reduced the survival rate after treatment with radiotherapy and temozolomide (RT
      TMZ) for glioma patients. The ectopic expression of TCTP enhanced glioma cell
      proliferation both in vitro and in vivo, whereas the knockdown of TCTP inhibited
      this effect. Similarly, the overexpression of TCTP increased beta-catenin binding
      to TCF-4, TOPflash report gene transcription activity, and the expression of
      Wnt/beta-catenin signaling target genes including c-Myc and cyclin D1; notably,
      the knockdown of TCTP reduced these effects. The knockdown of TCF-4 using shRNA
      rescued the enhanced cell proliferation induced by the overexpression of TCTP.
      Conclusion TCTP is associated with reduced survival of glioma patients and
      induces glioma tumor growth through enhanced Wnt/beta-catenin signaling. 

PMID- 24311646
TI  - What awaits the new NSF director.

PMID- 24311651
TI  - Animal rights. Lawsuits seek 'personhood' for chimpanzees.

PMID- 24311653
TI  - Russia. A painful cure for ailing academy.

PMID- 24311652
TI  - Human Evolution. Elusive Denisovans sighted in oldest human DNA.

PMID- 24311654
TI  - Neuroscience. Faulty brain connections in dyslexia?

PMID- 24311656
TI  - Genes for extremes.

PMID- 24311657
TI  - From toxins to treatments.

PMID- 24311658
TI  - The Freek show.

PMID- 24311659
TI  - Island of the snakes.

PMID- 24311660
TI  - Science communication: Narratively speaking.

PMID- 24311661
TI  - Science communication: Power of community.

PMID- 24311662
TI  - Science communication: Quality at stake.

PMID- 24311663
TI  - Science communication: Flawed citation indexing.

PMID- 24311664
TI  - Science communication: Self-publishing's benefits.

PMID- 24311665
TI  - Comment on "Poverty impedes cognitive function".
AB  - Mani et al. (Research Articles, 30 August, p. 976) presented laboratory
      experiments that aimed to show that poverty-related worries impede cognitive
      functioning. A reanalysis without dichotomization of income fails to corroborate
      their findings and highlights spurious interactions between income and
      experimental manipulation due to ceiling effects caused by short and easy tests.
      This suggests that effects of financial worries are not limited to the poor. 

PMID- 24311666
TI  - Response to comment on "Poverty impedes cognitive function".
AB  - Wicherts and Scholten criticized our study on statistical and psychometric
      grounds. We show that (i) using a continuous income variable, the interaction
      between income, and experimental manipulation remains reliable across our
      experiments; (ii) our results in the cognitive control task do not appear driven
      by ceiling effects; and (iii) our observed post-harvest improvement is robust to
      the presence of learning. 

PMID- 24311668
TI  - Technology. Advanced manufacturing policies and paradigms for innovation.

PMID- 24311669
TI  - Evolution. How fisheries affect evolution.

PMID- 24311670
TI  - Immunology. Do T cells have a cilium?

PMID- 24311671
TI  - Geophysics. Dangers of being thin and weak.

PMID- 24311672
TI  - Botany. Shining light at microtubule crossroads.

PMID- 24311673
TI  - Physics. Freeing nonlinear optics from phase matching.

PMID- 24311674
TI  - Development. Permission to proliferate.

PMID- 24311675
TI  - Science & SciLifeLab Prize. From persistence to cross-species emergence of a
      viral zoonosis.

PMID- 24311676
TI  - Science & SciLifeLab Prize. Stop, go, and evolve.

PMID- 24311677
TI  - Science & SciLifeLab Prize. Assembly of a neural circuit.

PMID- 24311678
TI  - Science & SciLifeLab Prize. Evolution of vertebrate transcriptional regulator
      binding.

PMID- 24311679
TI  - Single-cell biology. Cells go solo. Introduction.

PMID- 24311680
TI  - Genetic determinants and cellular constraints in noisy gene expression.
AB  - In individual cells, transcription is a random process obeying single-molecule
      kinetics. Often, it occurs in a bursty, intermittent manner. The frequency and
      size of these bursts affect the magnitude of temporal fluctuations in messenger
      RNA and protein content within a cell, creating variation or "noise" in gene
      expression. It is still unclear to what degree transcriptional kinetics are
      specific to each gene and determined by its promoter sequence. Alternative
      scenarios have been proposed, in which the kinetics of transcription are governed
      by cellular constraints and follow universal rules across the genome. Evidence
      from genome-wide noise studies and from systematic perturbations of promoter
      sequences suggest that both scenarios-namely gene-specific versus genome-wide
      regulation of transcription kinetics-may be present to different degrees in
      bacteria, yeast, and animal cells. 

PMID- 24311681
TI  - Functional roles of pulsing in genetic circuits.
AB  - A fundamental problem in biology is to understand how genetic circuits implement
      core cellular functions. Time-lapse microscopy techniques are beginning to
      provide a direct view of circuit dynamics in individual living cells.
      Unexpectedly, we are discovering that key transcription and regulatory factors
      pulse on and off repeatedly, and often stochastically, even when cells are
      maintained in constant conditions. This type of spontaneous dynamic behavior is
      pervasive, appearing in diverse cell types from microbes to mammalian cells.
      Here, we review recent work showing how pulsing is generated and controlled by
      underlying regulatory circuits and how it provides critical capabilities to cells
      in stress response, signaling, and development. A major theme is the ability of
      pulsing to enable time-based regulation analogous to strategies used in
      engineered systems. Thus, pulsatile dynamics is emerging as a central, and still
      largely unexplored, layer of temporal organization in the cell. 

PMID- 24311682
TI  - Structure and composition of the plate-boundary slip zone for the 2011 Tohoku-Oki
      earthquake.
AB  - The mechanics of great subduction earthquakes are influenced by the frictional
      properties, structure, and composition of the plate-boundary fault. We present
      observations of the structure and composition of the shallow source fault of the
      2011 Tohoku-Oki earthquake and tsunami from boreholes drilled by the Integrated
      Ocean Drilling Program Expedition 343 and 343T. Logging-while-drilling and core
      sample observations show a single major plate-boundary fault accommodated the
      large slip of the Tohoku-Oki earthquake rupture, as well as nearly all the
      cumulative interplate motion at the drill site. The localization of deformation
      onto a limited thickness (less than 5 meters) of pelagic clay is the defining
      characteristic of the shallow earthquake fault, suggesting that the pelagic clay
      may be a regionally important control on tsunamigenic earthquakes. 

PMID- 24311683
TI  - Low coseismic shear stress on the Tohoku-Oki megathrust determined from
      laboratory experiments.
AB  - Large coseismic slip was thought to be unlikely to occur on the shallow portions
      of plate-boundary thrusts, but the 11 March 2011 Tohoku-Oki earthquake [moment
      magnitude (Mw) = 9.0] produced huge displacements of ~50 meters near the Japan
      Trench with a resultant devastating tsunami. To investigate the mechanisms of the
      very large fault movements, we conducted high-velocity (1.3 meters per second)
      friction experiments on samples retrieved from the plate-boundary thrust
      associated with the earthquake. The results show a small stress drop with very
      low peak and steady-state shear stress. The very low shear stress can be
      attributed to the abundance of weak clay (smectite) and thermal pressurization
      effects, which can facilitate fault slip. This behavior provides an explanation
      for the huge shallow slip that occurred during the earthquake. 

PMID- 24311685
TI  - Giant convection cells found on the Sun.
AB  - Heat is transported through the outermost 30% of the Sun's interior by
      overturning convective motions. These motions are evident at the Sun's surface in
      the form of two characteristic cellular structures: granules and supergranules
      (~1000 and ~30,000 kilometers across, respectively). The existence of much larger
      cells has been suggested by both theory and observation for more than 45 years.
      We found evidence for giant cellular flows that persist for months by tracking
      the motions of supergranules. As expected from the effects of the Sun's rotation,
      the flows in these cells are clockwise around high pressure in the north and
      counterclockwise in the south and transport angular momentum toward the equator,
      maintaining the Sun's rapid equatorial rotation. 

PMID- 24311684
TI  - Low coseismic friction on the Tohoku-Oki fault determined from temperature
      measurements.
AB  - The frictional resistance on a fault during slip controls earthquake dynamics.
      Friction dissipates heat during an earthquake; therefore, the fault temperature
      after an earthquake provides insight into the level of friction. The Japan Trench
      Fast Drilling Project (Integrated Ocean Drilling Program Expedition 343 and 343T)
      installed a borehole temperature observatory 16 months after the March 2011
      moment magnitude 9.0 Tohoku-Oki earthquake across the fault where slip was ~50
      meters near the trench. After 9 months of operation, the complete sensor string
      was recovered. A 0.31 degrees C temperature anomaly at the plate boundary fault
      corresponds to 27 megajoules per square meter of dissipated energy during the
      earthquake. The resulting apparent friction coefficient of 0.08 is considerably
      smaller than static values for most rocks. 

PMID- 24311686
TI  - Precision spectroscopy of polarized molecules in an ion trap.
AB  - Polar molecules are desirable systems for quantum simulations and cold chemistry.
      Molecular ions are easily trapped, but a bias electric field applied to polarize
      them tends to accelerate them out of the trap. We present a general solution to
      this issue by rotating the bias field slowly enough for the molecular
      polarization axis to follow but rapidly enough for the ions to stay trapped. We
      demonstrate Ramsey spectroscopy between Stark-Zeeman sublevels in (180)Hf(19)F(+)
      with a coherence time of 100 milliseconds. Frequency shifts arising from well
      controlled topological (Berry) phases are used to determine magnetic g factors.
      The rotating-bias-field technique may enable using trapped polar molecules for
      precision measurement and quantum information science, including the search for
      an electron electric dipole moment. 

PMID- 24311687
TI  - Phase mismatch-free nonlinear propagation in optical zero-index materials.
AB  - Phase matching is a critical requirement for coherent nonlinear optical processes
      such as frequency conversion and parametric amplification. Phase mismatch
      prevents microscopic nonlinear sources from combining constructively, resulting
      in destructive interference and thus very low efficiency. We report the
      experimental demonstration of phase mismatch-free nonlinear generation in a zero
      index optical metamaterial. In contrast to phase mismatch compensation techniques
      required in conventional nonlinear media, the zero index eliminates the need for
      phase matching, allowing efficient nonlinear generation in both forward and
      backward directions. We demonstrate phase mismatch-free nonlinear generation
      using intrapulse four-wave mixing, where we observed a forward-to-backward
      nonlinear emission ratio close to unity. The removal of phase matching in
      nonlinear optical metamaterials may lead to applications such as multidirectional
      frequency conversion and entangled photon generation. 

PMID- 24311688
TI  - Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling.
AB  - The skin is a classical example of a tissue maintained by stem cells. However,
      the identity of the stem cells that maintain the interfollicular epidermis and
      the source of the signals that control their activity remain unclear. Using mouse
      lineage tracing and quantitative clonal analyses, we showed that the Wnt target
      gene Axin2 marks interfollicular epidermal stem cells. These Axin2-expressing
      cells constitute the majority of the basal epidermal layer, compete neutrally,
      and require Wnt/beta-catenin signaling to proliferate. The same cells contribute
      robustly to wound healing, with no requirement for a quiescent stem cell
      subpopulation. By means of double-labeling RNA in situ hybridization in mice, we
      showed that the Axin2-expressing cells themselves produce Wnt signals as well as
      long-range secreted Wnt inhibitors, suggesting an autocrine mechanism of stem
      cell self-renewal. 

PMID- 24311689
TI  - Preferential recognition of avian-like receptors in human influenza A H7N9
      viruses.
AB  - The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised
      concerns about its ability to transmit in the human population. The hemagglutinin
      glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to
      adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan
      array analysis of the H7 hemagglutinin reveals negligible binding to humanlike
      alpha2-6-linked receptors and strong preference for a subset of avian-like alpha2
      3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9
      hemagglutinin and six hemagglutinin-glycan complexes have elucidated the
      structural basis for preferential recognition of avian-like receptors. These
      findings suggest that the current human H7N9 viruses are poorly adapted for
      efficient human-to-human transmission. 

PMID- 24311690
TI  - HCF-1 is cleaved in the active site of O-GlcNAc transferase.
AB  - Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle
      progression, undergoes proteolytic maturation in which any of six repeated
      sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N
      acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the
      tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl
      terminal portion of an HCF-1 proteolytic repeat such that the cleavage region
      lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The
      conformation is similar to that of a glycosylation-competent peptide substrate.
      Cleavage occurs between cysteine and glutamate residues and results in a
      pyroglutamate product. Conversion of the cleavage site glutamate into serine
      converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus,
      protein glycosylation and HCF-1 cleavage occur in the same active site. 

PMID- 24311691
TI  - Nonredundant function of soluble LTalpha3 produced by innate lymphoid cells in
      intestinal homeostasis.
AB  - Immunoglobulin A (IgA) production at mucosal surfaces contributes to protection
      against pathogens and controls intestinal microbiota composition. However,
      mechanisms regulating IgA induction are not completely defined. We show that
      soluble lymphotoxin alpha (sLTalpha3) produced by RORgammat(+) innate lymphoid
      cells (ILCs) controls T cell-dependent IgA induction in the lamina propria via
      regulation of T cell homing to the gut. By contrast, membrane-bound lymphotoxin
      beta (LTalpha1beta2) produced by RORgammat(+) ILCs is critical for T cell
      independent IgA induction in the lamina propria via control of dendritic cell
      functions. Ablation of LTalpha in RORgammat(+) cells abrogated IgA production in
      the gut and altered microbiota composition. Thus, soluble and membrane-bound
      lymphotoxins produced by ILCs distinctly organize adaptive immune responses in
      the gut and control commensal microbiota composition. 

PMID- 24311692
TI  - Hedgehog signaling controls T cell killing at the immunological synapse.
AB  - The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting
      the plasma membrane and directing cytotoxic granules for secretion at the
      immunological synapse. Centrosome docking at the plasma membrane also occurs
      during cilia formation. The primary cilium, formed in nonhematopoietic cells, is
      essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary
      cilia, but we found and describe here that Hh signaling played an important role
      in CTL killing. T cell receptor activation, which "prearms" CTLs with cytotoxic
      granules, also initiated Hh signaling. Hh pathway activation occurred
      intracellularly and triggered Rac1 synthesis. These events "prearmed" CTLs for
      action by promoting the actin remodeling required for centrosome polarization and
      granule release. Thus, Hh signaling plays a role in CTL function, and the
      immunological synapse may represent a modified cilium. 

PMID- 24311693
TI  - Intact but less accessible phonetic representations in adults with dyslexia.
AB  - Dyslexia is a severe and persistent reading and spelling disorder caused by
      impairment in the ability to manipulate speech sounds. We combined functional
      magnetic resonance brain imaging with multivoxel pattern analysis and functional
      and structural connectivity analysis in an effort to disentangle whether
      dyslexics' phonological deficits are caused by poor quality of the phonetic
      representations or by difficulties in accessing intact phonetic representations.
      We found that phonetic representations are hosted bilaterally in primary and
      secondary auditory cortices and that their neural quality (in terms of robustness
      and distinctness) is intact in adults with dyslexia. However, the functional and
      structural connectivity between the bilateral auditory cortices and the left
      inferior frontal gyrus (a region involved in higher-level phonological
      processing) is significantly hampered in dyslexics, suggesting deficient access
      to otherwise intact phonetic representations. 

PMID- 24311695
TI  - Single-cell metabolomics: analytical and biological perspectives.
AB  - There is currently much interest in broad molecular profiling of single cells; a
      cell's metabolome-its full complement of small-molecule metabolites-is a direct
      indicator of phenotypic diversity of single cells and a nearly immediate readout
      of how cells react to environmental influences. However, the metabolome is very
      difficult to measure at the single-cell level because of rapid metabolic
      dynamics, the structural diversity of the molecules, and the inability to amplify
      or tag small-molecule metabolites. Measurement techniques including mass
      spectrometry, capillary electrophoresis, and, to a lesser extent, optical
      spectroscopy and fluorescence detection have led to impressive advances in single
      cell metabolomics. Even though none of these methodologies can currently measure
      the metabolome of a single cell completely, rapidly, and nondestructively,
      progress has been sufficient such that the field is witnessing a shift from
      feasibility studies to investigations that yield new biological insight.
      Particularly interesting fields of application are cancer biology, stem cell
      research, and monitoring of xenobiotics and drugs in tissue sections at the
      single-cell level. 

PMID- 24311694
TI  - MicroRNA-128 governs neuronal excitability and motor behavior in mice.
AB  - The control of motor behavior in animals and humans requires constant adaptation
      of neuronal networks to signals of various types and strengths. We found that
      microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor
      behavior by modulating neuronal signaling networks and excitability. miR-128
      governs motor activity by suppressing the expression of various ion channels and
      signaling components of the extracellular signal-regulated kinase ERK2 network
      that regulate neuronal excitability. In mice, a reduction of miR-128 expression
      in postnatal neurons causes increased motor activity and fatal epilepsy.
      Overexpression of miR-128 attenuates neuronal responsiveness, suppresses motor
      activity, and alleviates motor abnormalities associated with Parkinson's-like
      disease and seizures in mice. These data suggest a therapeutic potential for miR
      128 in the treatment of epilepsy and movement disorders. 

PMID- 24311697
TI  - Detection of angiographically occult, ruptured cerebral aneurysms: case series
      and literature review.
AB  - BACKGROUND: Ruptured and thrombosed cerebral aneurysms pose a risk for rebleeding
      that may go undetected because they are angiographically occult. The presence of
      multiple aneurysms may further complicate efforts in accurately identifying the
      true source because their treatment may circumvent further necessary
      investigations. METHODS: This case series and literature review illustrates the
      background and clinical features of ruptured thrombosed cerebral aneurysms.
      RESULTS: Thrombosed ruptured cerebral aneurysms have several common anatomic and
      physiologic mechanisms for their occurrence. They may evade detection if not
      considered part of a diligent thorough approach that includes careful analysis of
      the pattern of initial bleeding on non-contrast head CT scan. CONCLUSIONS:
      Despite negative angiographic studies, and even when multiple cerebral aneurysms
      are present, diffuse subrachnoid hemorrhage may still warrant further
      investigation.

PMID- 24311696
TI  - Overcoming the evening/weekend effects on time delays and outcomes of
      endovascular stroke therapy: the Calgary Stroke Program experience.
AB  - BACKGROUND: Stentrievers have resulted in faster recanalization times in patients
      with acute ischemic stroke. Nonetheless, when strokes occur during evenings and
      weekends, delays are introduced in achieving this goal. We assessed the
      feasibility of achieving fast and successful endovascular reperfusion in patients
      with stroke treated during evenings and weekends and whether this has an impact
      on the outcome. METHODS: A retrospective review was performed of a longitudinal
      database of patients with acute anterior ischemic stroke treated with
      endovascular therapy in a comprehensive stroke center between January 2011 and
      December 2012. The imaging to reperfusion time was defined as the time from
      completion of the unenhanced CT scan to the time of angiographic successful
      reperfusion (TICI 2b-3). This time interval was compared between patients treated
      during working hours (Monday to Friday 07:00-18:00 h) and those treated in the
      evening outside these hours and at weekends. The 24-h NIH Stroke Scale score and
      90-day favorable outcome score (modified Rankin scale <=2) were compared between
      the two groups. RESULTS: In a cohort of 110 patients, 56 (50.9%) were treated on
      evenings and weekends. The median imaging to reperfusion time in these patients
      was 111 min compared with 90 min during working hours (p=0.019). The proportion
      of patients with successful reperfusion (TICI 2b or 3) during the evenings and
      weekends was 82.1% compared with 76.7% during working hours (p=0.4). The
      proportion of patients with a 90-day favorable outcome was not significantly
      different in the two groups (64.3% in those treated during evenings and weekends
      vs 52.1% in working hours, p=0.2). CONCLUSIONS: Some delays were encountered
      during evenings and weekend hours. Despite that, it was feasible to achieve a
      relatively short imaging to reperfusion times during these hours, in comparison
      to existing literature. A target universal time metric is needed to assess the
      timeliness of endovascular therapy in stroke centers.

PMID- 24311698
TI  - The reach ratio--a new indicator for comparing quitline reach into smoking
      subgroups.
AB  - INTRODUCTION: There is growing concern about population disparities in tobacco
      related morbidity and mortality. This paper introduces the reach ratio as a
      complementary measure to reach for monitoring whether quitline interventions are
      reaching high risk groups of smokers proportionate to their prevalence in the
      population. METHODS: Data on smokers were collected at intake by 7 Canadian
      provincial quitlines from 2007 to 2009 and grouped to identify 4 high risk
      subgroups: males, young adults, heavy smokers, and those with low education.
      Provincial data are from the Canadian Tobacco Use Monitoring Survey. Reach ratios
      (ReRas), defined as the proportion of quitline callers from a subgroup divided by
      the proportion of the smoking population in the subgroup, and 95% confidence
      intervals were calculated for the subgroups. A ReRa of 1.0 indicates
      proportionate representation. RESULTS: ReRas for male smokers and young adults
      are consistently less than 1.0 across all provinces, indicating that a lower
      proportion of these high-risk smokers were receiving evidence-based smoking
      cessation treatment from quitlines. Those with high levels of tobacco addiction
      and less than high school education have ReRas greater than 1.0, indicating that
      a greater proportion of these smokers were receiving cessation treatments.
      CONCLUSION: ReRas complement other measures of reach and provide a standardized
      estimate of the extent to which subgroups of interest are benefiting from
      available cessation interventions. This information can help quitline operators,
      funders, and policymakers determine the need for promotional strategies targeted
      to high risk subgroups, and allocate resources to meet program and policy
      objectives.

PMID- 24311699
TI  - Concise review: microfluidic technology platforms: poised to accelerate
      development and translation of stem cell-derived therapies.
AB  - Stem cells are a powerful resource for producing a variety of cell types with
      utility in clinically associated applications, including preclinical drug
      screening and development, disease and developmental modeling, and regenerative
      medicine. Regardless of the type of stem cell, substantial barriers to clinical
      translation still exist and must be overcome to realize full clinical potential.
      These barriers span processes including cell isolation, expansion, and
      differentiation; purification, quality control, and therapeutic efficacy and
      safety; and the economic viability of bioprocesses for production of functional
      cell products. Microfluidic systems have been developed for a myriad of
      biological applications and have the intrinsic capability of controlling and
      interrogating the cellular microenvironment with unrivalled precision; therefore,
      they have particular relevance to overcoming such barriers to translation.
      Development of microfluidic technologies increasingly utilizes stem cells,
      addresses stem cell-relevant biological phenomena, and aligns capabilities with
      translational challenges and goals. In this concise review, we describe how
      microfluidic technologies can contribute to the translation of stem cell research
      outcomes, and we provide an update on innovative research efforts in this area.
      This timely convergence of stem cell translational challenges and microfluidic
      capabilities means that there is now an opportunity for both disciplines to
      benefit from increased interaction. 

PMID- 24311700
TI  - Enhancement of polysialic acid expression improves function of embryonic stem
      derived dopamine neuron grafts in Parkinsonian mice.
AB  - There has been considerable progress in obtaining engraftable embryonic stem (ES)
      cell-derived midbrain dopamine neurons for cell replacement therapy in models of
      Parkinson's disease; however, limited integration and striatal reinnervation of
      ES-derived grafts remain a major challenge for future clinical translation. In
      this paper, we show that enhanced expression of polysialic acid results in
      improved graft efficiency in correcting behavioral deficits in Parkinsonian mice.
      This result is accompanied by two potentially relevant cellular changes: greater
      survival of transplanted ES-derived dopamine neurons and robust sprouting of
      tyrosine hydroxylase-positive processes into host tissue. Because the procedures
      used to enhance polysialic acid are easily translated to other cell types and
      species, this approach may represent a general strategy to improve graft
      integration in cell-based therapies. 

PMID- 24311701
TI  - Concurrent generation of functional smooth muscle and endothelial cells via a
      vascular progenitor.
AB  - Smooth muscle cells (SMCs) and endothelial cells (ECs) are typically derived
      separately, with low efficiencies, from human pluripotent stem cells (hPSCs). The
      concurrent generation of these cell types might lead to potential applications in
      regenerative medicine to model, elucidate, and eventually treat vascular
      diseases. Here we report a robust two-step protocol that can be used to
      simultaneously generate large numbers of functional SMCs and ECs from a common
      proliferative vascular progenitor population via a two-dimensional culture
      system. We show here that coculturing hPSCs with OP9 cells in media supplemented
      with vascular endothelial growth factor, basic fibroblast growth factor, and bone
      morphogenetic protein 4 yields a higher percentage of CD31(+)CD34(+) cells on day
      8 of differentiation. Upon exposure to endothelial differentiation media and SM
      differentiation media, these vascular progenitors were able to differentiate and
      mature into functional endothelial cells and smooth muscle cells, respectively.
      Furthermore, we were able to expand the intermediate population more than a
      billion fold to generate sufficient numbers of ECs and SMCs in parallel for
      potential therapeutic transplantations.

PMID- 24311702
TI  - The risk of radiation-induced breast cancers due to biennial mammographic
      screening in women aged 50-69 years is minimal.
AB  - BACKGROUND: The main aim of mammographic screening is to reduce the mortality
      from breast cancer. However, use of ionizing radiation is considered a potential
      harm due to the possible risk of inducing cancer in healthy women. PURPOSE: To
      estimate the potential number of radiation-induced breast cancers, radiation
      induced breast cancer deaths, and lives saved due to implementation of organized
      mammographic screening as performed in Norway. MATERIAL AND METHODS: We used a
      previously published excess absolute risk model which assumes a linear no
      threshold dose-response. The estimates were calculated for 100,000 women aged 50
      69 years, a screening interval of 2 years, and with an assumed follow-up until
      the age of 85 or 105 years. Radiation doses of 0.7, 2.5, and 5.7 mGy per
      screening examination, a latency time of 5 or 10 years, and a dose and dose-rate
      effectiveness factor (DDREF) of 1 or 2 were applied. RESULTS: The total lifetime
      risk of radiation-induced breast cancers per 100,000 women was 10 (95% CI: 4-25)
      if the women were followed from the ages of 50 to 85 years, for a dose of 2.5
      mGy, a latency time of 10 years, and a DDREF of 1. For the same parameter values
      the number of radiation-induced breast cancer death was 1 (95% CI: 0-2). The
      assumed number of lives saved is approximately 350. CONCLUSION: The risk of
      radiation-induced breast cancer and breast cancer death due to mammographic
      screening is minimal. Women should not be discouraged from attending screening
      due to fear of radiation-induced breast cancer death.

PMID- 24311703
TI  - Contrast material and radiation dose reduction strategy for triple-rule-out
      cardiac CT angiography: feasibility study of non-ECG-gated low kVp scan of the
      whole chest following coronary CT angiography.
AB  - BACKGROUND: Dedicated coronary computed tomography (CT) scan has been proven to
      be an accurate diagnostic modality in evaluating coronary artery disease. A
      second phase scan starting immediately after the coronary CT scan might enable
      visualization of the different vascular territories of the entire chest. PURPOSE:
      To investigate the feasibility of a contrast material and radiation dose
      reduction triple-rule-out (TRO) CT angiography (CTA) protocol with serial non-ECG
      gated low kVp scan of the whole chest, which utilizes a recirculated contrast
      agent. MATERIAL AND METHODS: Thirty patients were scanned with the new TRO-CTA
      protocol; after the coronary scan with retrospective ECG-gating, non-ECG-gated
      whole-chest CTA was performed at 80 kVp to evaluate aortic arch (AAr) and
      pulmonary trunk (PT). Another 30 patients were scanned by our conventional TRO
      CTA protocol at 120 kVp with retrospective ECG-gating. We compared the estimated
      effective dose (ED), contrast material (CM) dose, contrast-to-noise ratio (CNR)
      of the ascending aorta (AAo), and the rate of patients who could achieve adequate
      attenuation of the AAr and PT between the two protocols. RESULTS: The total ED of
      the new TRO-CTA protocol was 29.6% lower than that of the conventional protocol
      (P < 0.01). The amount of CM used for the new TRO-CTA protocol was significantly
      lower than in the conventional protocol (60.1 +/- 9.6 mL vs. 91.8 +/- 22.6 mL, P
      < 0.01). The CNR of the AAo was 30.2% higher with the new TRO-CTA protocol than
      with the conventional protocol (P < 0.01). There was no significant difference in
      the success rate of adequate attenuation of the AAr and PT between the two
      protocols (P > 0.05). CONCLUSION: The new TRO-CTA protocol can reduce the total
      dose of radiation and the contrast dose and yield adequate vascular enhancement
      compared with the conventional protocol.

PMID- 24311704
TI  - Disordered FGF23 and mineral metabolism in children with CKD.
AB  - BACKGROUND AND OBJECTIVES: In children with CKD, information is limited regarding
      the prevalence and determinants of fibroblast growth factor 23 excess and 1,25
      dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study
      characterized circulating concentrations of fibroblast growth factor 23 and 1,25
      dihyroxyvitamin D, and investigated their interrelationships and associations
      with GFR and secondary hyperparathyroidism in children with CKD who were enrolled
      in the Chronic Kidney Disease in Children observational cohort study. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma fibroblast growth factor 23
      concentrations and determinants of mineral metabolism were measured in 464
      children ages 1-16 years with predialysis CKD. GFR was measured by plasma
      disappearance of iohexol in 70% of participants and estimated by the Chronic
      Kidney Disease in Children estimating equation using serum creatinine and
      cystatin C concentrations in the remainder of the participants. Participants were
      grouped according to CKD stage and by 10-ml/min categories of GFR. RESULTS:
      Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57;
      range=15-109). Plasma fibroblast growth factor 23 concentration was above the
      normal range in 67% of participants (with higher levels observed among
      participants with lower GFR) before higher levels of serum parathyroid hormone
      and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34%
      higher in participants with glomerular disease than in participants with
      nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for
      age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher
      GFR, but thereafter they became higher in parallel with fibroblast growth factor
      23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in
      those participants with low GFR values, high fibroblast growth factor 23 levels,
      25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism
      was present in 55% of participants with GFR<50 ml/min per 1.73 m(2). CONCLUSION:
      In children with predialysis CKD, high plasma fibroblast growth factor 23 is the
      earliest detectable abnormality in mineral metabolism, and levels are highest in
      glomerular diseases.

PMID- 24311705
TI  - Plasma ceruloplasmin, a regulator of nitric oxide activity, and incident
      cardiovascular risk in patients with CKD.
AB  - BACKGROUND AND OBJECTIVES: Increased serum levels of the acute-phase reactant
      ceruloplasmin predict adverse clinical outcomes in the setting of acute coronary
      syndromes and heart failure, but their role in patients with CKD is unclear. This
      study investigated the relationship of ceruloplasmin with clinical outcomes in
      CKD, especially with regard to traditional cardiac biomarkers. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Serum ceruloplasmin levels in consecutive study
      participants with CKD (n=654; estimated GFR<60 ml/min per 1.73 m(2)) as well as a
      control group of non-CKD participants matched for age and sex (n=250) were
      measured. Study participants were enrolled during 2001-2006 from a population of
      patients presenting for elective diagnostic coronary angiography and
      prospectively followed for 3 years (median follow-up=1095 days) to determine
      incident major adverse cardiac events (defined as a composite of death, nonfatal
      myocardial infarction, and stroke). RESULTS: Serum ceruloplasmin levels in CKD
      patients were elevated versus controls (median [interquartile range]; 25.5 [21.8
      29.6] versus 22.7 [19.7-26.5] mg/dl; P<0.001) and associated with increased risk
      of future major adverse cardiac events (hazard ratio, 1.35; 95% confidence
      interval, 1.0 to 1.82; P=0.04). After adjusting for traditional risk factors,
      higher serum ceruloplasmin was still associated with higher risk of major adverse
      cardiac events at 3 years (hazard ratio, 1.61; 95% confidence interval, 1.15 to
      2.25; P=0.01). CONCLUSION: In CKD patients, increased serum ceruloplasmin, a
      regulator of nitric oxide activity, is associated with increased risk of long
      term adverse cardiovascular events, even after multivariable model adjustment for
      traditional clinical and biologic risk factors.

PMID- 24311706
TI  - Kidney stones and cardiovascular events: a cohort study.
AB  - BACKGROUND AND OBJECTIVES: Kidney stones are common in general clinical practice,
      and their prevalence is increasing. Kidney stone formers often have risk factors
      associated with atherosclerosis, but it is uncertain whether having a kidney
      stone is associated with higher risk of cardiovascular events. This study sought
      to assess the association between one or more kidney stones and the subsequent
      risk of cardiovascular events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Cohort study of 3,195,452 people aged>=18 years registered in the universal
      health care system in Alberta, Canada, between 1997 and 2009 (median follow-up of
      11 years). People undergoing dialysis or with a kidney transplant at baseline
      were excluded. The primary outcome was the first acute myocardial infarction
      (AMI) during follow-up. We also considered other cardiovascular events, including
      death due to coronary heart disease, percutaneous transluminal coronary
      angioplasty (PTCA), coronary artery bypass grafting (CABG), and stroke. RESULTS:
      In total, 25,532 (0.8%) participants had at least one kidney stone, and 91,465
      (3%) individuals had at least one cardiovascular event during follow-up. Compared
      with people without kidney stones and after adjustment for cardiovascular risk
      factors and other potential confounders, people who had at least one kidney stone
      had a higher risk of subsequent AMI (adjusted hazard ratio [HR], 1.40; 95%
      confidence interval [95% CI], 1.30 to 1.51), PTCA/CABG (HR, 1.63; 95% CI, 1.51 to
      1.76), and stroke (HR, 1.26; 95% CI, 1.12 to 1.42). The magnitude of the excess
      risk associated with a kidney stone appeared more pronounced for younger people
      than for older people (P<0.001) and for women than men (P=0.01). CONCLUSIONS: The
      occurrence of a kidney stone is associated with a higher risk of cardiovascular
      events, including AMI, PTCA/CABG, and stroke.

PMID- 24311707
TI  - Generalizability of genetic findings related to kidney function and albuminuria.

PMID- 24311708
TI  - Association between AKI and long-term renal and cardiovascular outcomes in United
      States veterans.
AB  - BACKGROUND AND OBJECTIVES: AKI is associated with major adverse kidney events
      (MAKE): death, new dialysis, and worsened renal function. CKD (arising from
      worsened renal function) is associated with a higher risk of major adverse
      cardiac events (MACE): myocardial infarction (MI), stroke, and heart failure.
      Therefore, the study hypothesis was that veterans who develop AKI during
      hospitalization for an MI would be at higher risk of subsequent MACE and MAKE.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients in the Veterans Affairs
      (VA) database who had a discharge diagnosis with International Classification of
      Diseases, Ninth Revision, code of 584.xx (AKI) or 410.xx (MI) and were admitted
      to a VA facility from October 1999 through December 2005 were selected for
      analysis. Three groups of patients were created on the basis of the index
      admission diagnosis and serum creatinine values: AKI, MI, or MI with AKI.
      Patients with mean baseline estimated GFR<45 ml/min per 1.73 m(2) were excluded.
      The primary outcomes assessed were mortality, MAKE, and MACE during the study
      period (maximum of 6 years). The combination of MAKE and MACE-major adverse
      renocardiovascular events (MARCE)-was also assessed. RESULTS: A total of 36,980
      patients were available for analysis. Mean age+/-SD was 66.8+/-11.4 years. The
      most deaths occurred in the MI+AKI group (57.5%), and the fewest (32.3%) occurred
      in patients with an uncomplicated MI admission. In both the unadjusted and
      adjusted time-to-event analyses, patients with AKI and AKI+MI had worse MARCE
      outcomes than those who had MI alone (adjusted hazard ratios, 1.37 [95%
      confidence interval, 1.32 to 1.42] and 1.92 [1.86 to 1.99], respectively).
      CONCLUSIONS: Veterans who develop AKI in the setting of MI have worse long-term
      outcomes than those with AKI or MI alone. Veterans with AKI alone have worse
      outcomes than those diagnosed with an MI in the absence of AKI.

PMID- 24311709
TI  - Renal parenchymal area and risk of ESRD in boys with posterior urethral valves.
AB  - BACKGROUND AND OBJECTIVES: Approximately 20% of boys with posterior urethral
      valves develop ESRD; however, few factors associated with the risk of ESRD have
      been identified. The objective of this study was to determine if renal
      parenchymal area, defined as the area of the kidney minus the area of the
      pelvicaliceal system on first postnatal ultrasound, is associated with the risk
      of ESRD in infants with posterior urethral valves. DESIGN, SETTING, PARTICIPANTS,
      & MEASUREMENTS: A retrospective cohort of boys who were diagnosed with posterior
      urethral valves at less than 6 months of age between 1988 and 2011 and followed
      for at least 1 year at a free-standing children's hospital was assembled. Cox
      proportional hazard regression and Kaplan-Meier analysis were used to estimate
      the association between renal parenchymal area and time to ESRD. Cox models were
      adjusted for age at presentation, minimum creatinine 1 month after bladder
      decompression, and vesicoureteral reflux. RESULTS: Sixty patients were followed
      for 393 person-years. Eight patients developed ESRD. Median renal parenchymal
      area was 15.9 cm(2) (interquartile range=13.0-21.6 cm(2)). Each 1-cm(2) increase
      in renal parenchymal area was associated with a lower risk of ESRD (hazard ratio,
      0.64; 95% confidence interval, 0.42 to 0.98). The rate of time to ESRD was 10
      times higher in boys with renal parenchymal area<12.4 cm(2) than boys with renal
      parenchymal area>=12.4 cm(2) (P<0.001). Renal parenchymal area could best
      discriminate children at risk for ESRD when the minimum creatinine in the first 1
      month after bladder decompression was between 0.8 and 1.1 mg/dl. CONCLUSION: In
      boys with posterior urethral valves presenting during the first 6 months of life,
      lower renal parenchymal area is associated with an increased risk of ESRD during
      childhood. The predictive ability of renal parenchymal area, which is available
      at time of diagnosis, should be validated in a larger, prospectively-enrolled
      cohort.

PMID- 24311710
TI  - Subacute kidney injury in hospitalized patients.
AB  - BACKGROUND AND OBJECTIVES: The epidemiology of AKI and CKD has been described.
      However, the epidemiology of progressively worsening kidney function (subacute
      kidney injury [s-AKI]) developing over a longer time frame than defined for AKI
      (7 days), but shorter than defined for CKD (90 days), is completely unknown.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective study used a
      hospital laboratory and admission database. Adult patients admitted to a teaching
      hospital in Tokyo, Japan, between April 1, 2008, and October 31, 2011, were
      included. s-AKI was classified into three grades of severity (mild, moderate,
      severe) in accordance with the Risk, Injury, and Failure categories of the Risk,
      Injury, Failure, Risk, Loss, and ESRD classification, but did not use its time
      frame. Kidney injury (AKI and s-AKI) occurring during each hospital stay was
      identified, and logistic regression analysis was performed to assess their effect
      on hospital mortality. RESULTS: Of 56,567 patients admitted to the hospital
      during the study period, 49,518 were included. Of these, 87.8% had no evidence of
      kidney dysfunction, 11.0% had AKI, and 1.1% had s-AKI. Patients with s-AKI had
      mild renal dysfunction in 82.7% of cases, moderate in 12.1%, and severe in 5.0%.
      Worsening s-AKI category was linearly correlated with hospital mortality, as
      previously described for AKI (no injury: 1.2%, mild: 6.5%, moderate: 12.9%,
      severe: 20.7%). Although mortality (8.0% versus 17.5%) and need for renal
      replacement therapy (0.2% versus 2.2%) were lower in patients with s-AKI than in
      those with AKI, multivariable regression analysis confirmed that s-AKI was an
      independent risk factor for hospital mortality (odds ratio (OR), 5.44; 95%
      confidence interval [95% CI], 3.89 to 7.44); the OR with AKI was 14.8 (95% CI,
      13.2 to 16.7). CONCLUSIONS: Close to 1% of hospitalized patients develop s-AKI.
      This condition is independently associated with increased hospital mortality, and
      the risk for death increases with s-AKI severity. Patients with s-AKI had a
      better outcome and were less likely to require renal replacement therapy than
      patients with AKI.

PMID- 24311711
TI  - Generalization of associations of kidney-related genetic loci to American
      Indians.
AB  - BACKGROUND AND OBJECTIVES: CKD disproportionally affects American Indians, who
      similar to other populations, show genetic susceptibility to kidney outcomes.
      Recent studies have identified several loci associated with kidney traits, but
      their relevance in American Indians is unknown. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This study used data from a large, family-based genetic study of
      American Indians (the Strong Heart Family Study), which includes 94
      multigenerational families enrolled from communities located in Oklahoma, the
      Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a
      population-based study of cardiovascular disease in American Indians. This study
      selected 25 single nucleotide polymorphisms in 23 loci identified from recently
      published kidney-related genome-wide association studies in individuals of
      European ancestry to evaluate their associations with kidney function (estimated
      GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria
      (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study.
      This study also examined the association of single nucleotide polymorphisms in
      the APOL1 region with estimated GFR in 1121 Strong Heart Family Study
      participants. GFR was estimated using the abbreviated Modification of Diet in
      Renal Disease Equation. Additive genetic models adjusted for age and sex were
      used. RESULTS: This study identified significant associations of single
      nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2,
      PIP5K1B, and WDR72 (P<2.1 * 10(-3) to account for multiple testing). Single
      nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total
      variance and 2.9% of its heritability. An intronic variant of BCAS3 was
      significantly associated with urinary albumin to creatinine ratio. APOL1 single
      nucleotide polymorphisms were not associated with estimated GFR in a single
      variant test or haplotype analyses, and the at-risk variants identified in
      individuals with African ancestry were not detected in DNA sequencing of American
      Indians. CONCLUSION: This study extends the genetic associations of loci
      affecting kidney function to American Indians, a population at high risk of
      kidney disease, and provides additional support for a potential biologic
      relevance of these loci across ancestries.

PMID- 24311712
TI  - A comorbidity index for mortality prediction in Chinese patients with ESRD
      receiving hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Chinese patients with ESRD have different comorbidity
      patterns than white patients with ESRD and require a validated comorbidity index.
      The objective of this study was to develop a new index for mortality prediction
      in 2006-2009 Taiwanese incident hemodialysis patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Data were retrieved from 2005 to 2010 Taiwan
      National Health Insurance claim records, and follow-up was available until
      December 31, 2010. The same comorbid conditions as the US Renal Data System
      (USRDS) index that occurred during a 12-month period from 9 months before to 3
      months after dialysis initiation were used to construct the index. Integer weight
      of the comorbid conditions was derived from coefficient estimates of Cox
      regression for all-cause mortality, and the index was internally validated. The
      performance of the index was assessed by discrimination, calibration, and
      reclassification. RESULTS: A total of 30,303 hemodialysis patients were included
      in this study. The weight for individual comorbid conditions of this index
      differed from that of the USRDS index. The performance of this index was similar
      to that of USRDS and Charlson indices in terms of model fit statistics, overall
      predictive ability, discrimination, and calibration. Hosmer-Lemeshow test showed
      that all three indices demonstrated significant differences between predicted and
      observed mortality rates. When patients were categorized by the predicted 2.5
      year survival probabilities, the index achieved a net reclassification
      improvement of 4.71% (P<0.001), referenced to USRDS index. CONCLUSIONS: Compared
      with USRDS index, this new index demonstrated better reclassification ability,
      but future studies should address the clinical significance.

PMID- 24311713
TI  - Neonatal GATA1 mutant clones under the radar.
AB  - In this issue of Blood, Roberts et al report the comprehensive screening of a
      large cohort of Down syndrome neonates for the transient abnormal myelopoiesis
      (TAM) disorder based on blood cell morphology review and screening for GATA1
      mutations, the signature genetic marker of TAM.

PMID- 24311714
TI  - The hemangioblast: a state of competence.
AB  - In this issue of Blood, Myers and Krieg present an elegant series of experiments,
      which suggest that the hemangioblast may be a state of competence rather than a
      bipotential progenitor state that exists in vivo.

PMID- 24311715
TI  - Maintenance in CLL.
AB  - In this issue of Blood, Abrisqueta and colleagues report on the outcomes of a
      phase 2 clinical trial evaluating rituximab maintenance therapy in chronic
      lymphocytic leukemia (CLL) patients after treatment with rituximab, fludarabine,
      cyclophosphamide, and mitoxantrone (R-FCM).

PMID- 24311716
TI  - Busulfan or TBI: answer to an age-old question.
AB  - In this issue of Blood, authors of 2 articles have compared busulfan with total
      body irradiation (TBI) in preparative regimens for hematopoietic transplantation
      as treatment of acute myeloid leukemia (AML).

PMID- 24311717
TI  - New specs for arteriovenous identity.
AB  - In this issue of Blood, Aranguren et al. provide new insights into the molecular
      mechanisms that determine the identity of human endothelial cells: i.e., will
      they line arteries or veins? The findings have implications in our understanding
      of vascular disease and in the design of vascular-specific therapies and tissue
      engineering.

PMID- 24311718
TI  - Selective E-selectin ligands.
AB  - In this issue of Blood, Sreeramkumar and colleagues report that E-selectin ligand
      1 (ESL-1) is a highly selective ligand for E-selectin on hematopoietic
      progenitors with unexpected important contributions to their trafficking.

PMID- 24311719
TI  - Increases in levels of epoxyeicosatrienoic and dihydroxyeicosatrienoic acids
      (EETs and DHETs) in liver and heart in vivo by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) and in hepatic EET:DHET ratios by cotreatment with TCDD and the
      soluble epoxide hydrolase inhibitor AUDA.
AB  - The environmental toxin and carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD,
      dioxin) binds and activates the transcription factor aryl hydrocarbon receptor
      (AHR), inducing CYP1 family cytochrome P450 enzymes. CYP1A2 and its avian
      ortholog CYP1A5 are highly active arachidonic acid epoxygenases. Epoxygenases
      metabolize arachidonic acid to four regioisomeric epoxyeicosatrienoic acids
      (EETs) and selected monohydroxyeicosatetraenoic acids (HETEs). EETs can be
      further metabolized by epoxide hydrolases to dihydroxyeicosatrienoic acids
      (DHETs). As P450-arachidonic acid metabolites affect vasoregulation, responses to
      ischemia, inflammation, and metabolic disorders, identification of their
      production in vivo is needed to understand their contribution to biologic effects
      of TCDD and other AHR activators. Here we report use of an acetonitrile-based
      extraction procedure that markedly increased the yield of arachidonic acid
      products by lipidomic analysis over a standard solid-phase extraction protocol.
      We show that TCDD increased all four EETs (5,6-, 8,9-, 11,12-, and 14,15-), their
      corresponding DHETs, and 18- and 20-HETE in liver in vivo and increased 5,6-EET,
      the four DHETs, and 18-HETE in heart, in a chick embryo model. As the chick
      embryo heart lacks arachidonic acid-metabolizing activity, the latter findings
      suggest that arachidonic acid metabolites may travel from their site of
      production to a distal organ, i.e., heart. To determine if the TCDD-arachidonic
      acid-metabolite profile could be altered pharmacologically, chick embryos were
      treated with TCDD and the soluble epoxide hydrolase inhibitor 12-(3-adamantan-1
      yl-ureido)-dodecanoic acid (AUDA). Cotreatment with AUDA increased hepatic EET-to
      DHET ratios, indicating that the in vivo profile of P450-arachidonic acid
      metabolites can be modified for potential therapeutic intervention. 

PMID- 24311721
TI  - Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T
      cell engager (BiTE) antibody, AMG 330, against human AML.
AB  - CD33 is a valid target for acute myeloid leukemia (AML) but has proven
      challenging for antibody-drug conjugates. Herein, we investigated the cellular
      determinants for the activity of the novel CD33/CD3-directed bispecific T-cell
      engager antibody, AMG 330. In the presence of T cells, AMG 330 was highly active
      against human AML cell lines and primary AML cells in a dose- and effector to
      target cell ratio-dependent manner. Using cell lines engineered to express wild
      type CD33 at increased levels, we found a quantitative relationship between AMG
      330 cytotoxicity and CD33 expression; in contrast, AMG 330 cytotoxicity was
      neither affected by common CD33 single nucleotide polymorphisms nor expression of
      the adenosine triphosphate-binding cassette (ABC) transporter proteins, P
      glycoprotein or breast cancer resistance protein. Unlike bivalent CD33
      antibodies, AMG 330 did not reduce surface CD33 expression. The epigenetic
      modifier drugs, panobinostat and azacitidine, increased CD33 expression in some
      cell lines and augmented AMG 330-induced cytotoxicity. These findings demonstrate
      that AMG 330 has potent CD33-dependent cytolytic activity in vitro, which can be
      further enhanced with other clinically available therapeutics. As it neither
      modulates CD33 expression nor is affected by ABC transporter activity, AMG 330 is
      highly promising for clinical exploration as it may overcome some limitations of
      previous CD33-targeted agents. 

PMID- 24311722
TI  - Bruton's tyrosine kinase (BTK) function is important to the development and
      expansion of chronic lymphocytic leukemia (CLL).
AB  - Chronic lymphocytic leukemia (CLL) is characterized by constitutive activation of
      the B-cell receptor (BCR) signaling pathway, but variable responsiveness of the
      BCR to antigen ligation. Bruton's tyrosine kinase (BTK) shows constitutive
      activity in CLL and is the target of irreversible inhibition by ibrutinib, an
      orally bioavailable kinase inhibitor that has shown outstanding activity in CLL.
      Early clinical results in CLL with other reversible and irreversible BTK
      inhibitors have been less promising, however, raising the question of whether BTK
      kinase activity is an important target of ibrutinib and also in CLL. To determine
      the role of BTK in CLL, we used patient samples and the EMU-TCL1 (TCL1)
      transgenic mouse model of CLL, which results in spontaneous leukemia development.
      Inhibition of BTK in primary human CLL cells by small interfering RNA promotes
      apoptosis. Inhibition of BTK kinase activity through either targeted genetic
      inactivation or ibrutinib in the TCL1 mouse significantly delays the development
      of CLL, demonstrating that BTK is a critical kinase for CLL development and
      expansion and thus an important target of ibrutinib. Collectively, our data
      confirm the importance of kinase-functional BTK in CLL. 

PMID- 24311723
TI  - Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year
      follow-up from a randomized phase 3 trial (DASISION).
AB  - This analysis explores the impact of early cytogenetic and molecular responses on
      the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP)
      in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients
      trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP
      were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n =
      260) once daily. The retrospective landmark analysis included patients evaluable
      at the relevant time point (3, 6, or 12 months). Median time to complete
      cytogenetic response was 3 vs 6 months with dasatinib vs imatinib. At 3 and 6
      months, the proportion of patients with BCR-ABL transcript levels <=10% was
      higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were
      observed in a higher proportion of patients on dasatinib therapy and were
      associated with better 3-year progression-free survival and overall survival in
      both arms. First-line dasatinib resulted in faster and deeper responses compared
      with imatinib. The achievement of an early molecular response was predictive of
      improved progression-free survival and overall survival, supporting new
      milestones for optimal response in patients with early CML-CP treated with
      tyrosine kinase inhibitors. This study was registered at www.clinicaltrials.gov
      as NCT00481247. 

PMID- 24311724
TI  - Association of fentanyl with neurodevelopmental outcomes in very-low-birth-weight
      infants.
AB  - BACKGROUND: Opioids are commonly used in the neonatal intensive care unit (NICU).
      Negative neurodevelopmental effects in the short-term setting have been
      associated with opioids ; however, long-term studies have been limited.
      OBJECTIVE: The primary objective was to determine if there is a dose relationship
      between fentanyl and neurodevelopmental outcomes, as measured by Bayley Scales of
      Infant and Toddler Development (Bayley-III) composite scores for language,
      cognition, and motor skills. Secondary objectives included comparison of Bayley
      III scores and neurodevelopmental impairment classification based on fentanyl
      exposure. METHODS: A retrospective evaluation of 147 very-low-birth-weight
      infants with Bayley-III scores obtained at a chronological age of 6 months to 2
      years at clinic follow-up was conducted. Univariate and multivariable linear
      regression analyses were used to determine if there was a dose-related
      association between fentanyl and neurodevelopmental outcomes. To evaluate
      secondary outcomes, patients were divided based on cumulative fentanyl dose
      ("high-dose" versus "low/no-dose"). RESULTS: The univariate analysis found a
      statistically significant decrease in cognition (P = .034) and motor skills
      scores (P = .006). No association was found in the multi-variable regression
      between fentanyl cumulative dose and Bayley-III scores. There was a significant
      decrease in the motor skills score between the high-dose versus low/no-dose
      group, 94 +/- 20 versus 102 +/- 15, respectively (P = .026); however, no
      statistical differences were noted for language or cognition scores or
      neurological impairment classification. CONCLUSIONS: When controlling for other
      variables, the cumulative fentanyl dose did not correlate with neurodevelopmental
      outcomes. Further evaluation of benefits and risks of opioids in premature
      infants are needed.

PMID- 24311725
TI  - Pediatric exclusivity: evolving legislation and novel complexities within
      pediatric therapeutic development.
AB  - OBJECTIVE: To review the successes and omissions of the Food and Drug
      Administration (FDA) pediatric exclusivity incentive. DATA SOURCES: Pediatric
      drug development receives less attention and funding than drug development
      targeting adults resulting in fewer appropriately labeled pediatric drugs. Newly
      introduced legislation aims to correct this deficit using market exclusivity
      incentives. Under the Food and Drug Administration Modernization Act (FDAMA,
      1997), the FDA established the exclusivity principle. This legislation was
      renewed and amended in 2007 under Food and Drug Administration Amendments Act
      (FDAAA) allowing drug companies to receive a 6-month patent extension for
      initiating clinical investigation in pediatric populations. Fostering improved
      knowledge in pediatric indications and dosing is the motivating force behind this
      program. STUDY SELECTION AND DATA EXTRACTION: We examined drugs granted
      exclusivity through FDA published database as well as relevant drug labeling and
      postmarket safety studies. Our examination shows that studies conducted in
      support of patent protection are often not designed to meet current pediatric
      needs. CONCLUSION: Amendments to FDAAA are needed to ensure that studies approved
      for exclusivity strive to meet the following requirements: relevant pediatric
      clinical indication ; disease addressed should represent a significant disease
      burden to the appropriate population; important age ranges should be covered;
      studies should not be allowed when a safety signal is identified prior to
      initiation of the study; and trials where endpoints are successfully achieved
      providing considerable contribution to pediatric dosing knowledge or result in
      labeling changes may gain an additional incentive.

PMID- 24311726
TI  - Retracted: Response to comment on "Intravenous sodium bicarbonate therapy in
      severely acidotic diabetic ketoacidosis".

PMID- 24311727
TI  - Early symptom improvement and discontinuation of 5-alpha-reductase inhibitor
      (5ARI) therapy in patients with benign prostatic hyperplasia (BPH).
AB  - BACKGROUND: Pharmacological treatment options for benign prostatic hyperplasia
      (BPH) commonly include alpha-blocker (AB) and 5-alpha-reductase inhibitor (5ARI)
      agents, which have separate but important attributes that carry clinical
      implications in terms of improvement of lower-urinary tract symptoms (LUTS) and
      clinical disease progression. OBJECTIVES: This study hypothesized that
      administering AB therapy concomitantly with newly started 5ARI treatment would
      reduce the likelihood of 5ARI discontinuation through early symptom improvement.
      METHODS: This retrospective analysis of the PharMetrics Integrated Medical and
      Pharmaceutical Database included men aged >=50 years with >=1 medical claim of
      BPH diagnosis and >=1 prescription claim of a 5ARI with or without an AB.
      Patients initiating 5ARI monotherapy were propensity score matched with patients
      initiating combination AB + 5ARI therapy (1:1), with 5ARI time to discontinuation
      (30-day gap in treatment) compared between groups utilizing survival analysis
      techniques. The percentage of patients adherent to 5ARI therapy based on
      medication possession ratio (MPR) was assessed. RESULTS: After 180 days of follow
      up, 61.7% of the combination therapy arm versus 59.2% of the monotherapy arm
      remained on therapy. Combination therapy patients were 10% less likely to
      discontinue 5ARI treatment (hazard ratio = 0.904; P = .006) and were more likely
      to be adherent when adherence was defined as MPR >=70% and >=75%. CONCLUSIONS:
      Based on an assessment of claims data, initiating AB with 5ARI therapy is
      associated with a lower rate of 5ARI discontinuation compared with 5ARI
      monotherapy. Early symptom relief from AB therapy may contribute to a lower
      discontinuation rate for concomitant 5ARI therapy.

PMID- 24311728
TI  - Prevalence of depression and antidepressant therapy use in a pediatric cystic
      fibrosis population.
AB  - BACKGROUND: Depression is associated with significant morbidity and mortality. In
      recent years reports of depression in cystic fibrosis (CF) patients of all ages
      have increased. As awareness of depression in CF increases, there remains limited
      data regarding the prevalence and management of depression in the pediatric CF
      population. OBJECTIVES: To assess the prevalence of depression, describe
      depression treatment regimens, and identify risk factors for depression in the
      pediatric CF population at a single care center. METHODS: A retrospective chart
      review was conducted on 190 patients at 1 accredited CF center. Patient
      demographics and clinical characteristics were collected and compared between
      patients with depression and patients without depression. In addition, the
      treatment strategies of patients with depression were recorded. RESULTS: The
      number of patients with a documented diagnosis of depression was found to be 9%,
      and 50% of these patients were prescribed antidepressant therapy. The most common
      class of medication prescribed for depression in these patients was the selective
      serotonin reuptake inhibitors, where fluoxetine was the most common medication.
      Patients with depression had a lower mean absolute forced expiratory volume in 1
      s (1.88 vs 2.48 L; P = .042), more than 5 total hospitalizations per year (4 vs
      1; P = .012), and more outpatient CF exacerbations requiring treatment (1.5 vs 0;
      P = .023) per year than patients without depression. CONCLUSION: Identified risk
      factors may be used to increase depression screening of CF pediatric patients,
      allowing for early detection and screening in this potentially high-risk patient
      population. More studies are needed to determine efficacious treatment for
      depression in pediatric CF patients.

PMID- 24311729
TI  - Response to "lorcaserin and phentermine/topiramate: two leaps forward in weight
      loss pharmacotherapy".

PMID- 24311730
TI  - TorsinA rescues ER-associated stress and locomotive defects in C. elegans models
      of ALS.
AB  - Molecular mechanisms underlying neurodegenerative diseases converge at the
      interface of pathways impacting cellular stress, protein homeostasis and aging.
      Targeting the intrinsic capacities of neuroprotective proteins to restore
      neuronal function and/or attenuate degeneration represents a potential means
      toward therapeutic intervention. The product of the human DYT1 gene, torsinA, is
      a member of the functionally diverse AAA+ family of proteins and exhibits robust
      molecular-chaperone-like activity, both in vitro and in vivo. Although mutations
      in DYT1 are associated with a rare form of heritable generalized dystonia, the
      native function of torsinA seems to be cytoprotective in maintaining the cellular
      threshold to endoplasmic reticulum (ER) stress. Here we explore the potential for
      torsinA to serve as a buffer to attenuate the cellular consequences of misfolded
      protein stress as it pertains to the neurodegenerative disease amyotrophic
      lateral sclerosis (ALS). The selective vulnerability of motor neurons to
      degeneration in ALS mouse models harboring mutations in superoxide dismutase
      (SOD1) has been found to correlate with regional-specific ER stress in brains.
      Using Caenorhabditis elegans as a system to model ER stress, we generated
      transgenic nematodes overexpressing either wild-type or mutant human SOD1 to
      evaluate their relative impact on ER stress induction in vivo. These studies
      revealed a mutant-SOD1-specific increase in ER stress that was further
      exacerbated by changes in temperature, all of which was robustly attenuated by co
      expression of torsinA. Moreover, through complementary behavioral analysis,
      torsinA was able to restore normal neuronal function in mutant G85R SOD1 animals.
      Furthermore, torsinA targeted mutant SOD1 for degradation via the proteasome,
      representing mechanistic insight on the activity that torsinA has on aggregate
      prone proteins. These results expand our understanding of proteostatic mechanisms
      influencing neuronal dysfunction in ALS, while simultaneously highlighting the
      potential for torsinA as a novel target for therapeutic development. 

PMID- 24311732
TI  - How can we recognize continuous quality improvement?
AB  - OBJECTIVE: Continuous quality improvement (CQI) methods are foundational
      approaches to improving healthcare delivery. Publications using the term CQI,
      however, are methodologically heterogeneous, and labels other than CQI are used
      to signify relevant approaches. Standards for identifying the use of CQI based on
      its key methodological features could enable more effective learning across
      quality improvement (QI) efforts. The objective was to identify essential
      methodological features for recognizing CQI. DESIGN: Previous work with a 12
      member international expert panel identified reliably abstracted CQI
      methodological features. We tested which features met rigorous a priori standards
      as essential features of CQI using a three-phase online modified-Delphi process.
      SETTING: Primarily United States and Canada. PARTICIPANTS: 119 QI experts
      randomly assigned into four on-line panels. INTERVENTION: Participants rated CQI
      features and discussed their answers using online, anonymous and asynchronous
      discussion boards. We analyzed ratings quantitatively and discussion threads
      qualitatively. Main outcome measure(s) Panel consensus on definitional CQI
      features. RESULTS: /st> Seventy-nine (66%) panelists completed the process.
      Thirty-three completers self-identified as QI researchers, 18 as QI practitioners
      and 28 as both equally. The features 'systematic data guided activities,'
      'designing with local conditions in mind' and 'iterative development and testing'
      met a priori standards as essential CQI features. Qualitative analyses showed
      cross-cutting themes focused on differences between QI and CQI. CONCLUSIONS: We
      found consensus among a broad group of CQI researchers and practitioners on three
      features as essential for identifying QI work more specifically as 'CQI.' All
      three features are needed as a minimum standard for recognizing CQI methods.

PMID- 24311733
TI  - Antidepressant use has doubled in rich nations in past 10 years.

PMID- 24311731
TI  - A zebrafish model of chordoma initiated by notochord-driven expression of
      HRASV12.
AB  - Chordoma is a malignant tumor thought to arise from remnants of the embryonic
      notochord, with its origin in the bones of the axial skeleton. Surgical resection
      is the standard treatment, usually in combination with radiation therapy, but
      neither chemotherapeutic nor targeted therapeutic approaches have demonstrated
      success. No animal model and only few chordoma cell lines are available for
      preclinical drug testing, and, although no druggable genetic drivers have been
      identified, activation of EGFR and downstream AKT-PI3K pathways have been
      described. Here, we report a zebrafish model of chordoma, based on stable
      transgene-driven expression of HRASV12 in notochord cells during development.
      Extensive intra-notochordal tumor formation is evident within days of transgene
      expression, ultimately leading to larval death. The zebrafish tumors share
      characteristics of human chordoma as demonstrated by immunohistochemistry and
      electron microscopy. The mTORC1 inhibitor rapamycin, which has some demonstrated
      activity in a chordoma cell line, delays the onset of tumor formation in our
      zebrafish model, and improves survival of tumor-bearing fish. Consequently, the
      HRASV12-driven zebrafish model of chordoma could enable high-throughput screening
      of potential therapeutic agents for the treatment of this refractory cancer. 

PMID- 24311734
TI  - Prevention of cataracts by statins: a meta-analysis.
AB  - BACKGROUND: Current data indicate a persisting concern about possible
      cataractogenecity of statins. OBJECTIVE: To perform a meta-analysis of studies
      pertaining to statins and cataract. METHODS: We identified 363 records by a
      systematic search of the MedLine, Web of Knowledge, Cochrane database, and
      ClinicalTrials.gov. After exclusion of duplicates, studies without cataract as an
      outcome, reviews, and animal or basic science studies, we analyzed 14 studies.
      Two end points were examined: clinical cataract (requiring extraction or reported
      by the patient) and lens opacities discovered by slit-lamp examination. RESULTS:
      Using random effects meta-analysis, a statistically significant decrease in
      cataracts with statins was observed among studies examining clinical cataract
      (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.71-0.93, P = .0022).
      Absolute risk reduction was 1.4% +/- 0.015%, 95% CI 1.1%-1.7%, P < .0001,
      corresponding to 71, 95% CI 59-91, number needed to treat. The effect was larger
      for the harder end point of cataract extraction (OR 0.66, 95% CI 0.61-0.71, P <
      .0001). Metaregression indicated an increase in benefit with longer duration of
      statin use with OR varying from 0.54 for a treatment duration of 14 years to 0.95
      for a treatment duration of 6 months. Older age was associated with lower benefit
      (OR 1.03 for persons in their 70s to OR 0.49 for persons in their 40s), and there
      were no differences by gender. Several sensitivity analyses confirmed the
      results. Limitations of this analysis include the combination of randomized and
      observational studies and imprecise ascertainment of exposure and incomplete
      adjustment for confounders in several observational studies. CONCLUSION: This
      meta-analysis indicates a clinically relevant protective effect of statins in
      preventing cataracts. The effect is more pronounced in younger patients and with
      longer duration of follow-up, while there is no difference by gender.

PMID- 24311735
TI  - Antivirals for Bell's palsy?
AB  - Each year in the UK around 1 in 5,000 people develop Bell's palsy-idiopathic
      unilateral lower motor neurone facial weakness of rapid onset. Although about 70%
      recover spontaneously, the remaining 30% are at risk of complications;(1) 13%
      have residual slight weakness and about 16% have persistent moderate to severe
      weakness if not treated.(2) As we have discussed in two previous articles there
      has been longstanding controversy about the best form of treatment.(2,3) In 2006
      we concluded that published trials on the efficacy of drug treatments have been
      poor and no firm conclusions can be drawn about the benefit of any single
      drug;(2) in 2008 we noted that evidence suggests oral prednisolone started within
      72 hours of symptom onset makes recovery more likely and that there was little
      good evidence that an antiviral drug helps.(3) The place of antivirals in the
      management of Bell's palsy remains a controversial issue. In this article we
      review the evidence for antiviral therapy alone or in conjunction with
      corticosteroid treatment. 

PMID- 24311736
TI  - Expectations and experiences of investigators and parents involved in a clinical
      trial for Duchenne/Becker muscular dystrophy.
AB  - BACKGROUND: The social context of rare disease research is changing, with
      increased community engagement around drug development and clinical trials. This
      engagement may benefit patients and families but may also lead to heightened
      trial expectations and therapeutic misconception. Clinical investigators are also
      susceptible to harboring high expectations. Little is known about parental
      motivations and expectations for clinical trials for rare pediatric disorders.
      PURPOSE: We describe the experience of parents and clinical investigators
      involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy:
      their expectations, hopes, motivations, and reactions to the termination of the
      trial. METHODS: This qualitative study was based on interviews with clinical
      investigators and parents of sons with Duchenne and Becker muscular dystrophy
      (DBMD) who participated in the phase IIa or IIb ataluren clinical trial in the
      United States. Interviews were transcribed and coded for thematic analysis.
      RESULTS: Participants were 12 parents of affected boys receiving active drug and
      9 clinical investigators. High trial expectations of direct benefit were reported
      by parents and many clinicians. Investigators described monitoring and managing
      parents' expectations; several worried about their own involvement in increasing
      parents' expectations. Most parents were able to differentiate their expectations
      from their optimistic hopes for a cure. Parents' expectations arose from other
      parents, advocacy organizations, and the sponsor. All parents reported some
      degree of clinical benefit to their children. Secondary benefits were hopefulness
      and powerful feelings associated with active efforts to affect the disease
      course. Parents and clinical investigators reported strong, close relationships
      that were mutually important. Parents and clinicians felt valued by the sponsor
      for the majority of the trial. When the trial abruptly stopped, they described
      loss of engagement, distress, and feeling unprepared for the possibility of trial
      termination. LIMITATIONS: This was a retrospective study of one clinical trial.
      We were unable to recruit participants whose children received placebo. The
      interviews occurred during a time of significant uncertainty and distress for
      many of the participants. CONCLUSION: This pilot study reflects complex outcomes
      of strong community engagement. The findings highlight a need for renewed
      education about, and support for, clinical trial termination and loss of drug
      access. The primary positive outcome was demonstration of strong relationships
      among committed parents and study teams. These relationships were highly valued
      by both parties and may suggest an ideal intervention opportunity for efforts to
      improve psychological well-being. A negative outcome attributed, in part, to
      community engagement was inappropriately high trial expectations. More
      optimistically, high expectations were attributed, in part, to the importance of
      hope and powerful feelings associated with active efforts to affect the disease
      course.

PMID- 24311740
TI  - Chronic achilles rupture repair by allograft with bone block fixation: technique
      tip.

PMID- 24311739
TI  - Upregulation of zinc transporter 2 in the blood-CSF barrier following lead
      exposure.
AB  - Zinc (Zn) is an essential element for normal brain function; an abnormal Zn
      homeostasis in brain and the cerebrospinal fluid (CSF) has been implied in the
      etiology of Alzheimer's disease (AD). However, the mechanisms that regulate Zn
      transport in the blood-brain interface remain unknown. This study was designed to
      investigate Zn transport by the blood-CSF barrier (BCB) in the choroid plexus,
      with a particular focus on Zn transporter-2 (ZnT2), and to understand if lead
      (Pb) accumulation in the choroid plexus disturbed the Zn regulatory function in
      the BCB. Confocal microscopy, quantitative PCR and western blot demonstrated the
      presence of ZnT2 in the choroidal epithelia; ZnT2 was primarily in cytosol in
      freshly isolated plexus tissues but more toward the peripheral membrane in
      established choroidal Z310 cells. Exposure of rats to Pb (single ip injection of
      50 mg Pb acetate/kg) for 24 h increased ZnT2 fluorescent signals in plexus
      tissues by confocal imaging and protein expression by western blot. Similar
      results were obtained by in vitro experiments using Z310 cells. Further studies
      using cultured cells and a two-chamber Transwell device showed that Pb treatment
      significantly reduced the cellular Zn concentration and led to an increased
      transport of Zn across the BCB, the effect that may be due to the increased ZnT2
      by Pb exposure. Taken together, these results indicate that ZnT2 is present in
      the BCB; Pb exposure increases the ZnT2 expression in choroidal epithelial cells
      by a yet unknown mechanism and as a result, more Zn ions may be deposited into
      the intracellular Zn pool, leading to a relative Zn deficiency state in the
      cytoplasm at the BCB.

PMID- 24311741
TI  - A Model for Strengthening Collaborative Research Capacity: Illustrations From the
      Atlanta Clinical Translational Science Institute.
AB  - INTRODUCTION: Community-engaged research is effective in addressing health
      disparities but may present challenges for both academic institutions and
      community partners. Therefore, the need to build capacity for conducting
      collaborative research exists. The purpose of this study is to present a model
      for building research capacity in academic-community partnerships. METHOD: The
      Building Collaborative Research Capacity Model was developed as part of the
      Community Engagement Research Program (CERP) of the Atlanta Clinical and
      Translational Science Institute (ACTSI). Six domains of collaborative research
      capacity were identified and used to develop a model. Inputs, activities,
      outputs, and outcomes of building collaborative research capacity are described.
      RESULTS: To test this model, a competitive request for applications was widely
      distributed and four community-based organizations were funded to participate in
      a 2-year program with the aim of conducting a pilot study and submitting a
      research proposal for funding to National Institutes of Health or another major
      funding agency. During the first year, the community-based organization partners
      were trained on conducting collaborative research and matched with an academic
      partner from an ACTSI institution. Three of the academic-community partnerships
      submitted pilot study results and two submitted a grant proposal to a national
      agency. DISCUSSION: The Building Collaborative Research Capacity Model is an
      innovative approach to strengthening academic-community partnerships. This model
      will help build needed research capacity, serve as a framework for academicians
      and community partners, and lead to sustainable partnerships that improve
      community health.

PMID- 24311742
TI  - Epidemiology of penicillin-non-susceptible pneumococci in Iceland, 1995-2010.
AB  - OBJECTIVES: The first penicillin-non-susceptible pneumococci (PNSP) were
      identified in Iceland in 1988. A rapid increase followed, associated with
      expansion of a single multiresistant clone, Spain(6B)-2, peaking at 19.8% in
      1993. After interventions led to reduced antimicrobial use in children, the
      prevalence of PNSP decreased until 1995. The aim of this study was to follow the
      evolution of PNSP from 1995 to 2010, the period preceding the introduction of
      conjugated pneumococcal vaccines into the vaccination programme. METHODS: The
      laboratory at the Landspitali University Hospital serves ~ 85% of the Icelandic
      population. All pneumococci isolated from 1995 to 2010 (n = 13,937) were stored (
      80  degrees C). Oxacillin-resistant isolates were serotyped and penicillin MICs
      were determined. Selected strains were genotyped by PFGE and multilocus sequence
      typing. RESULTS: In 1995, the rate of PNSP was 24.2%, declining to 13.6% in 2001,
      and then increasing to 38.6% in 2010. Similar changes were observed for
      resistance to erythromycin and tetracycline. In 1995, 60.7% of PNSP were serotype
      6B, mainly the Spain(6B)-2 clone, declining to 5.7% in 2010. PNSP of serotype 19F
      rapidly increased after 2004 to comprise 85.8% of all serogrouped PNSP in 2010,
      with most isolates belonging to a single multiresistant PFGE clone identified as
      sequence type (ST) 271 and ST1968, representing single- and double-locus variants
      of the international clone Taiwan(19F)-14, respectively. PNSP were most common
      among young children, from the nasopharynx, middle ear and lower respiratory
      tract. CONCLUSIONS: The epidemiology of PNSP was dominated by two multiresistant
      clones. The second expanded rapidly when the first one was disappearing, causing
      higher antibiotic resistance rates among pneumococci than seen before in Iceland.

PMID- 24311743
TI  - Training professionals' communication and motivation skills to improve spinal
      cord injury patients' satisfaction and clinical outcomes: Study protocol of the
      ESPELMA trial.
AB  - Acute spinal cord injury leaves patients severely impaired and generates high
      levels of psychological distress among them and their families, which can cause a
      less active role in rehabilitation, worse functional recovery, and less perceived
      satisfaction with the results. Additionally, rehabilitation professionals who
      deal with this psychological distress could ultimately experience higher stress
      and more risk of burnout. This article presents the study protocol of the ESPELMA
      project, aimed to train rehabilitation professionals in the clinical management
      of acute spinal cord injury-associated psychological distress, and to measure the
      impact of this training on the patients' perceived satisfaction with treatment. 

PMID- 24311744
TI  - Two world views: Perspectives on autistic behaviours.
AB  - This article reports on a study, utilising phenomenological methodology, which
      used interview and video narratives to collect data from 10 young people with
      autism and their parents. Data analysis employed multistage, primarily
      ethnomethodological methods in order to interpret and understand experiences of
      autism. The study found that parents, arguably influenced by the medical and
      psychological perspectives through which 'autism' has evolved, problematise what
      children with autism do as pathological. This article juxtaposes parents'
      understandings against how children with autism, themselves, account for what
      they do, by exploring respective accounts of children's obsessions and
      ritualistic behaviours. 

PMID- 24311745
TI  - Time course-dependent changes in the transcriptome of human skeletal muscle
      during recovery from endurance exercise: from inflammation to adaptive
      remodeling.
AB  - Reprogramming of gene expression is fundamental for skeletal muscle adaptations
      in response to endurance exercise. This study investigated the time course
      dependent changes in the muscular transcriptome after an endurance exercise trial
      consisting of 1 h of intense cycling immediately followed by 1 h of intense
      running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h
      postexercise from eight healthy, endurance-trained men. RNA was extracted from
      muscle. Differential gene expression was evaluated using Illumina microarrays and
      validated with qPCR. Gene set enrichment analysis identified enriched molecular
      signatures chosen from the Molecular Signatures Database. Three hours
      postexercise, 102 gene sets were upregulated [family wise error rate (FWER), P <
      0.05], including groups of genes related with leukocyte migration, immune and
      chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1
      signaling. Forty-eight hours postexercise, among 19 enriched gene sets (FWER, P <
      0.05), two gene sets related to actin cytoskeleton remodeling were upregulated.
      Ninety-six hours postexercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of
      which were upregulated, including gene groups related to chemokine signaling,
      cell stress management, and extracellular matrix remodeling. These data provide
      comprehensive insights into the molecular pathways involved in acute stress,
      recovery, and adaptive muscular responses to endurance exercise. The novel 96 h
      postexercise transcriptome indicates substantial transcriptional activity
      potentially associated with the prolonged presence of leukocytes in the muscles.
      This suggests that muscular recovery, from a transcriptional perspective, is
      incomplete 96 h after endurance exercise involving muscle damage. 

PMID- 24311746
TI  - Interaction between gastrocnemius medialis fascicle and Achilles tendon
      compliance: a new insight on the quick-release method.
AB  - The insufficient temporal resolution of imaging devices has made the analysis of
      very fast movements, such as those required to measure active muscle-tendon unit
      stiffness, difficult. Thus the relative contributions of tendon, aponeurosis, and
      fascicle to muscle-tendon unit compliance remain to be determined. The present
      study analyzed the dynamic interactions of fascicle, tendon, and aponeurosis in
      human gastrocnemius medialis during the first milliseconds of an ankle quick
      release movement, using high-frame-rate ultrasonography (2,000 frames/s). Nine
      subjects performed the tests in random order at six levels of maximal voluntary
      contraction (MVC) (30% to 80% of MVC). These tests were carried out with the
      ultrasound probe placed on the muscle belly and on the myotendinous junction.
      Tendon, muscle fascicle, and aponeurosis length changes were quantified in
      relation to shortening of the muscle-tendon unit during the first few
      milliseconds following the release. The tendon was the main contributor (around
      72%) to the shortening of the muscle-tendon unit, whereas the muscle fascicle and
      aponeurosis contributions were 18% and 10%, respectively. Because these
      structures can be considered in series, the quantified contributions can be
      regarded as relative contributions to muscle-tendon compliance. These
      contributions were not modified with the level of MVC or the time range used for
      the analysis between 10 and 25 ms. The constant contribution of tendon, muscle
      fascicle, and aponeurosis to muscle-tendon unit compliance may help to simplify
      the mechanism of compliance regulation and to maintain the important role of
      tendons in enhancing work output and movement efficiency. 

PMID- 24311738
TI  - The Na+/I- symporter (NIS): mechanism and medical impact.
AB  - The Na(+)/I(-) symporter (NIS) is the plasma membrane glycoprotein that mediates
      active I(-) transport in the thyroid and other tissues, such as salivary glands,
      stomach, lactating breast, and small intestine. In the thyroid, NIS-mediated I(-)
      uptake plays a key role as the first step in the biosynthesis of the thyroid
      hormones, of which iodine is an essential constituent. These hormones are crucial
      for the development of the central nervous system and the lungs in the fetus and
      the newborn and for intermediary metabolism at all ages. Since the cloning of NIS
      in 1996, NIS research has become a major field of inquiry, with considerable
      impact on many basic and translational areas. In this article, we review the most
      recent findings on NIS, I(-) homeostasis, and related topics and place them in
      historical context. Among many other issues, we discuss the current outlook on
      iodide deficiency disorders, the present stage of understanding of the
      structure/function properties of NIS, information gleaned from the
      characterization of I(-) transport deficiency-causing NIS mutations, insights
      derived from the newly reported crystal structures of prokaryotic transporters
      and 3-dimensional homology modeling, and the novel discovery that NIS transports
      different substrates with different stoichiometries. A review of NIS regulatory
      mechanisms is provided, including a newly discovered one involving a K(+) channel
      that is required for NIS function in the thyroid. We also cover current and
      potential clinical applications of NIS, such as its central role in the treatment
      of thyroid cancer, its promising use as a reporter gene in imaging and diagnostic
      procedures, and the latest studies on NIS gene transfer aimed at extending
      radioiodide treatment to extrathyroidal cancers, including those involving
      specially engineered NIS molecules. 

PMID- 24311737
TI  - Clinical and molecular genetics of the phosphodiesterases (PDEs).
AB  - Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that have the unique
      function of terminating cyclic nucleotide signaling by catalyzing the hydrolysis
      of cAMP and GMP. They are critical regulators of the intracellular concentrations
      of cAMP and cGMP as well as of their signaling pathways and downstream biological
      effects. PDEs have been exploited pharmacologically for more than half a century,
      and some of the most successful drugs worldwide today affect PDE function.
      Recently, mutations in PDE genes have been identified as causative of certain
      human genetic diseases; even more recently, functional variants of PDE genes have
      been suggested to play a potential role in predisposition to tumors and/or
      cancer, especially in cAMP-sensitive tissues. Mouse models have been developed
      that point to wide developmental effects of PDEs from heart function to
      reproduction, to tumors, and beyond. This review brings together knowledge from a
      variety of disciplines (biochemistry and pharmacology, oncology, endocrinology,
      and reproductive sciences) with emphasis on recent research on PDEs, how PDEs
      affect cAMP and cGMP signaling in health and disease, and what pharmacological
      exploitations of PDEs may be useful in modulating cyclic nucleotide signaling in
      a way that prevents or treats certain human diseases. 

PMID- 24311747
TI  - Intravenous phentolamine abolishes coronary vasoconstriction in response to mild
      central hypovolemia.
AB  - Animal studies indicate alpha-adrenergic coronary vasoconstriction helps maintain
      left ventricular function during physiological stress. Whether this process
      occurs in humans is unknown. In the current study, we used transthoracic Doppler
      echocardiography to test the effect of lower body negative pressure (LBNP) on
      coronary blood flow velocity (CBV, left anterior descending coronary artery) and
      myocardial function in eight young healthy subjects before and after systemic
      infusion of phentolamine, a nonselective alpha blocker. Heart rate (HR) and blood
      pressure (BP) were monitored on a beat-by-beat basis. Peak diastolic CBV and
      myocardial systolic and diastolic tissue velocities (Sm and Em), were quantified
      at baseline, and at -5 mmHg, -10 mmHg, and -15 mmHg LBNP. Coronary vascular
      resistance index (CVRI) was calculated as the quotient of diastolic BP and CBV.
      Phentolamine reduced baseline diastolic BP and increased HR but did not affect
      the reflex adjustments to LBNP. The reduction in CBV due to LBNP was blunted by
      phentolamine at -10 mmHg and -15 mmHg. Importantly, the increase in CVRI (i.e.,
      coronary vasoconstriction) was abolished by phentolamine at -5 mmHg (0.21 +/-
      0.06 vs. 0.83 +/- 0.13), -10 mmHg (0.24 +/- 0.03 vs. 1.68 +/- 0.31), and -15 mmHg
      (0.27 +/- 0.10 vs. 2.34 +/- 0.43). These data indicate that alpha-adrenergic
      coronary vasoconstriction is present during low levels of LBNP. With alpha
      blockade, more coronary flow is needed to maintain cardiac function. Our data
      suggest that alpha-adrenergic tone enhances coronary flow efficiency, presumably
      by redistributing flow from the epicardium to the endocardium. 

PMID- 24311749
TI  - Quantification of regional fractional ventilation in human subjects by
      measurement of hyperpolarized 3He washout with 2D and 3D MRI.
AB  - Multiple-breath washout hyperpolarized (3)He MRI was used to calculate regional
      parametric images of fractional ventilation (r) as the ratio of fresh gas
      entering a volume unit to the total end inspiratory volume of the unit. Using a
      single dose of inhaled hyperpolarized gas and a total acquisition time of under 1
      min, gas washout was measured by dynamic acquisitions during successive breaths
      with a fixed delay. A two-dimensional (2D) imaging protocol was investigated in
      four healthy subjects in the supine position, and in a second protocol the
      capability of extending the washout imaging to a three-dimensional (3D)
      acquisition covering the whole lungs was tested. During both protocols, subjects
      were breathing comfortably, only restricted by synchronization of breathing to
      the sequence timings. The 3D protocol was also successfully tested on one patient
      with cystic fibrosis. Mean r values from each volunteer were compared with global
      gas volume turnover, as calculated from flow measurement at the mouth divided by
      total lung volume (from MRI images), and a significant correlation (r = 0.74, P <
      0.05) was found. The effects of gravity on R were investigated, and an average
      decrease in r of 5.5%/cm (Deltar = 0.016 +/- 0.006 cm(-1)) from posterior to
      anterior was found in the right lung. Intersubject reproducibility of r imaging
      with the 2D and 3D protocol was tested, and a significant correlation between
      repeated experiments was found in a pixel-by-pixel comparison. The proposed
      methods can be used to measure r on a regional basis. 

PMID- 24311748
TI  - Absence of lateral gastrocnemius activity and differential motor unit behavior in
      soleus and medial gastrocnemius during standing balance.
AB  - In a standing position, the vertical projection of the center of mass passes in
      front of the ankle, which requires active plantar-flexor torque from the triceps
      surae to maintain balance. We recorded motor unit (MU) activity in the medial
      (MG) and lateral (LG) gastrocnemius muscle and the soleus (SOL) in standing
      balance and voluntary isometric contractions to understand the effect of
      functional requirements and descending drive from different neural sources on
      motoneuron behavior. Single MU activity was recorded in seven subjects with wire
      electrodes in the triceps surae. Two 3-min standing balance trials and several
      ramp-and-hold contractions were performed. Lateral gastrocnemius MU activity was
      rarely observed in standing. The lowest thresholds for LG MUs in ramp
      contractions were 20-35 times higher than SOL and MG MUs (P < 0.001). Compared
      with MUs from the SOL, MG MUs were intermittently active (P < 0.001), had higher
      recruitment thresholds (P = 0.022), and greater firing rate variability (P <
      0.001); this difference in firing rate variability was present in standing
      balance and isometric contractions. In SOL and MG MUs, both recruitment of new
      MUs (R(2) = 0.59-0.79, P < 0.01) and MU firing rates (R(2) = 0.05-0.40, P < 0.05)
      were associated with anterior-posterior and medio-lateral torque in standing. Our
      results suggest that the two heads of the gastrocnemius may operate in different
      ankle ranges with the larger MG being of primary importance when standing, likely
      due to its fascicle orientation. These differences in MU discharge behavior were
      independent of the type of descending neural drive, which points to a muscle
      specific optimization of triceps surae motoneurons. 

PMID- 24311751
TI  - Introducing John Mirowsky.

PMID- 24311750
TI  - Vascular endothelial function and oxidative stress are related to dietary niacin
      intake among healthy middle-aged and older adults.
AB  - We tested the hypothesis that vascular endothelial function and oxidative stress
      are related to dietary niacin intake among healthy middle-aged and older adults.
      In 127 men and women aged 48-77 yr, brachial artery flow-mediated dilation (FMD)
      was positively related to dietary niacin intake [%change (Delta): r = 0.20, P <
      0.05; mmDelta: r = 0.25, P < 0.01]. In subjects with above-average dietary niacin
      intake (>= 22 mg/day, NHANES III), FMD was 25% greater than in subjects with
      below-average intake (P < 0.05). Stepwise linear regression revealed that dietary
      niacin intake (above vs. below average) was an independent predictor of FMD
      (%Delta: beta = 1.8; mmDelta: beta = 0.05, both P < 0.05). Plasma oxidized low
      density lipoprotein, a marker of systemic oxidative stress, was inversely related
      to niacin intake (r = -0.23, P < 0.05) and was lower in subjects with above- vs.
      below-average niacin intake (48 +/- 2 vs. 57 +/- 2 mg/dl, P < 0.01). Intravenous
      infusion of the antioxidant vitamin C improved brachial FMD in subjects with
      below-average niacin intake (P < 0.001, n = 33), but not above-average (P > 0.05,
      n = 20). In endothelial cells sampled from the brachial artery of a subgroup,
      dietary niacin intake was inversely related to nitrotyrosine, a marker of
      peroxynitrite-mediated oxidative damage (r = -0.30, P < 0.05, n = 55), and
      expression of the prooxidant enzyme, NADPH oxidase (r = -0.44, P < 0.01, n = 37),
      and these markers were lower in subjects with above- vs. below-average niacin
      intake [nitrotyrosine: 0.39 +/- 0.05 vs. 0.56 +/- 0.07; NADPH oxidase: 0.38 +/-
      0.05 vs. 0.53 +/- 0.05 (ratio to human umbilical vein endothelial cell control),
      both P < 0.05]. Our findings support the hypothesis that higher dietary niacin
      intake is associated with greater vascular endothelial function related to lower
      systemic and vascular oxidative stress among healthy middle-aged and older
      adults.

PMID- 24311752
TI  - Depression and the sense of control: aging vectors, trajectories, and trends.
AB  - Adulthood trajectories of outcomes such as depression and the sense of control
      measure aspects of the human condition that Americans may view as objects of
      change. Social science should provide information on that progress, or its
      absence. Whether these trajectories change their shape, and how and why if they
      do, is important theoretically too. A range of birth cohorts coexist in time,
      place, and social relationship. Each cohort, as it goes through adulthood,
      follows in aggregate a path left by older ones, reshaping that path as it goes.
      The shapes of the trajectories, and the trends reshaping them, represent two
      inseparable aspects of the same phenomenon. This report describes methods for
      mapping aging trajectories and intercohort trends, using linear latent-growth
      models of relatively brief follow-up data (six years in the examples). The author
      reviews shared research ideals that led to the model: put theory into modeling,
      go where the data lead, use what you have, go beyond where you have been, and
      risk being precisely wrong. 

PMID- 24311754
TI  - (Un)Healthy immigrant citizens: naturalization and activity limitations in older
      age.
AB  - This research argues that immigrants' political, social, and economic
      incorporation experiences, which are embedded in individual life course
      trajectories and heavily influenced by governmental policies, play an important
      role in producing diverse health outcomes among older U.S. foreign-born persons.
      Using data from the 2008-2010 American Community Survey and 1998-2010 Integrated
      Health Interview Series, we demonstrate how naturalization, a key indicator of
      social and political inclusion, is related to functional health in midlife and
      older age. Consistent with the theoretical framework, we find that among those
      foreign-born who immigrated as children and young adults, naturalized citizens
      show better health at older ages compared with noncitizens, although this
      relationship is partly mediated by education. But among those older foreign-born
      who immigrated at middle and older ages, naturalized citizens report worse health
      compared with noncitizens. Moreover, this negative health selection into
      naturalization becomes stronger for those naturalizing after the 1996 Welfare
      Reform Act. 

PMID- 24311756
TI  - Stigma of a label: educational expectations for high school students labeled with
      learning disabilities.
AB  - Poorer outcomes for youth labeled with learning disabilities (LDs) are often
      attributed to the student's own deficiencies or cumulative disadvantage; but the
      more troubling possibility is that special education placement limits rather than
      expands these students' opportunities. Labeling theory partially attributes the
      poorer outcomes of labeled persons to stigma related to labels. This study uses
      data on approximately 11,740 adolescents and their schools from the Education
      Longitudinal Survey of 2002 to determine if stigma influences teachers' and
      parents' educational expectations for students labeled with LDs and labeled
      adolescents' expectations for themselves. Supporting the predictions of labeling
      theory, teachers and parents are more likely to perceive disabilities in, and
      hold lower educational expectations for labeled adolescents than for similarly
      achieving and behaving adolescents not labeled with disabilities. The negative
      effect of being labeled with LDs on adolescents' educational expectations is
      partially mechanized through parents' and particularly teachers' lower
      expectations. 

PMID- 24311755
TI  - Gender, traumatic events, and mental health disorders in a rural Asian setting.
AB  - Research shows a strong association between traumatic life experience and mental
      health and important gender differences in that relationship in the western
      European Diaspora; but much less is known about these relationships in other
      settings. We investigate these relationships in a poor rural Asian setting that
      recently experienced a decade-long armed conflict. We use data from 400 adult
      interviews in rural Nepal. The measures come from World Mental Health survey
      instruments clinically validated for this study population to measure depression,
      posttraumatic stress disorder, and intermittent explosive disorder. Our results
      demonstrate that traumatic life experience significantly increases the likelihood
      of mental health disorders in this setting, and that these traumatic experiences
      have a larger effect on the mental health of women than men. These findings offer
      important clues regarding the potential mechanisms producing gender differences
      in mental health in many settings. 

PMID- 24311757
TI  - The impact of neighborhood composition on work-family conflict and distress.
AB  - Theories of work-family conflict (WFC) and health remain limited because they
      emphasize individual-level antecedents to the exclusion of broader contexts, such
      as residential neighborhoods. We address this issue by focusing on the impact of
      neighborhood social composition on WFC. Among couples with children we assess
      whether socially similar neighbors relative to oneself reduce perceptions and
      mental health consequences of WFC, and whether these associations differ by
      gender. We argue that the convergence of similarities in residents' features
      relative to the respondent's own may affect WFC by influencing normative
      expectations about work and family, and assumptions of available support. We use
      data on intact families with at least one child between the ages of 9 and 16 from
      Toronto, Canada, linked to census data. Results highlight that greater similarity
      between respondents and residents reduces perceptions and consequences of WFC for
      women but not men. We discuss these findings in relation to neighborhood effects
      and mental health literature. 

PMID- 24311758
TI  - Social ties and adolescent sleep disruption.
AB  - Teens tend go to bed later, get less sleep, and report more daytime sleepiness.
      Medical research emphasizes biological determinants of teens' disrupted sleep
      (i.e., the timing of puberty and resultant drops in melatonin), rarely or
      inadequately considering youths' social ties as a determinant of sleep behaviors.
      Sociologists recognize how social ties affect health behaviors but have generally
      neglected sleep, especially among teens. Drawing on a sample of 974 teens from
      the Study of Early Child Care and Youth Development, this study controls for
      developmental and social relational factors to predict changes in youths' sleep
      patterns between 12 and 15 years of age. In general, social relational factors
      outperform developmental factors in determining youths' sleep patterns,
      particularly pointing to the importance of parental, peer, and school ties in
      promoting healthy sleep behaviors. The implications of these findings for further
      research are briefly discussed. 

PMID- 24311761
TI  - Enhanced detection of Legionnaires' disease by PCR testing of induced sputum and
      throat swabs.

PMID- 24311762
TI  - Arterial stiffness in patients with COPD: the role of systemic inflammation and
      the effects of pulmonary rehabilitation.
AB  - Clear evidence for an association between systemic inflammation and increased
      arterial stiffness in patients with chronic obstructive pulmonary disease (COPD)
      is lacking. Moreover, the effects of pulmonary rehabilitation on arterial
      stiffness are not well studied. We aimed to 1) confirm increased arterial
      stiffness in COPD; 2) evaluate its correlates including systemic inflammation;
      and 3) study whether or not it is influenced by pulmonary rehabilitation. Aortic
      pulse-wave velocity (APWV) was determined in 168 healthy volunteers, and APWV and
      inflammatory markers were determined in 162 COPD patients during baseline
      evaluation of a pulmonary rehabilitation programme. A complete post-pulmonary
      rehabilitation dataset was collected in 129 patients. It was found that APWV was
      increased in COPD patients when compared with controls, blood pressure and age
      predicted baseline APWV, and systemic inflammatory markers were not independently
      related to APWV. Although baseline APWV was predictive for the change in APWV
      after pulmonary rehabilitation (r= -0.77), on average APWV did not change (10.7
      +/- 2.7 versus 10.9 +/- 2.5 m.s(-1); p=0.339). Arterial stiffness in COPD is not
      related to systemic inflammation and does not respond to state-of-the-art
      pulmonary rehabilitation. These results emphasise the complexity of
      cardiovascular risk and its management in COPD.

PMID- 24311763
TI  - A 2-year randomised placebo-controlled trial of doxycycline for
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is characterised by lung cysts and airflow
      obstruction. Matrix metalloproteinases have been implicated in lung destruction
      in LAM. We performed a randomised, double-blind trial, comparing the matrix
      metalloproteinases inhibitor doxycycline with placebo on the progression of LAM.
      23 females with LAM were randomised to doxycycline 100 mg daily for 3 months
      followed by 200 mg daily for 21 months, or matched placebo. Lung function,
      exercise capacity, quality of life and matrix metalloproteinases levels were
      measured. 21 patients completed 6 months of treatment, 17 completed 1 year of
      treatment and 15 completed 2 years of treatment. Eight withdrew from the trial
      due, four due to a pneumothorax and four because of other reasons. The mean+/-sd
      decline in FEV1, the primary endpoint, did not differ between the groups being 
      90+/-154 mL.year(-1) in the placebo group and -123+/-246 mL.year(-1) in the
      doxycycline group (difference -32.5, 95% CI -213-148; p=0.35). Doxycycline had no
      effect upon vital capacity, gas transfer, shuttle walk distance or quality of
      life. Urine matrix metalloproteinases-9 measurements were lower with doxycycline
      treatment (p=0.03). Although with limited numbers we cannot completely exclude an
      effect of doxycycline, the lack of effect on any outcome makes it unlikely that
      doxycycline has a useful effect in LAM.

PMID- 24311764
TI  - Pulmonary matrix metalloproteinase-9 activity in mechanically ventilated children
      with respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) infection is a potent stimulus for airway
      epithelial expression of matrix metalloproteinase (MMP)-9. MMP-9 activity in vivo
      is a predictor of disease severity in children with RSV-induced respiratory
      failure. Human airway epithelial cells were infected with RSV A2 strain and
      analysed for MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 (a natural
      inhibitor of MMP-9) release. In addition, endotracheal samples from children with
      RSV-RF and controls (non-RSV pneumonia and nonlung disease controls) were
      analysed for MMP-9, TIMP-1, human neutrophil elastase and myeloperoxidase
      activity. RSV infection of airway epithelia was sufficient to rapidly induce MMP
      9 transcription and protein release. Pulmonary MMP-9 activity peaked at 48 h in
      infants with RSV-induced respiratory failure. In the RSV group, MMP-9 activity
      and MMP-9/TIMP-1 ratio imbalance predicted higher oxygen requirement and worse
      paediatric risk of mortality scores. The highest levels of human neutrophil
      elastase and myeloperoxidase activity were measured in the RSV cohort; however,
      unlike MMP-9, these neutrophil markers failed to predict disease severity. These
      results support the hypothesis that RSV is a potent stimulus for MMP-9 expression
      and release from human airway epithelium, and that MMP-9 is an important
      biomarker of disease severity in mechanically ventilated children with RSV lung
      infection.

PMID- 24311765
TI  - Ambient temperature and lung function in children with asthma in Australia.
AB  - The association between ambient temperature and lung function in children with
      asthma is still uncertain. A panel of 270 children (aged 7-12 years) with asthma
      was recruited from six Australian cities. They performed three successive forced
      expiratory manoeuvres twice daily for 4 weeks. The highest peak expiratory flow
      rate (PEF) and forced expiratory volume in 1 s (FEV1) were stored for each
      session. During the same period, data were obtained daily on ambient temperature,
      relative humidity and air pollution. Mixed models were used to examine the
      effects of temperature on lung function, controlling for individual
      characteristics and environmental factors. Ambient temperature was negatively
      related to both morning and evening PEF and FEV1 for 0-3 days lag. In general,
      the effects of temperature were stronger in males than in females for evening
      PEF, while the effects were stronger in females for evening FEV1. Children with
      asthma living in southern cities were more sensitive to high temperature than
      those in the northernmost city. Higher ambient temperature is associated with
      lower lung function in children with asthma. Preventive health policies will be
      required to protect children with asthma from increasingly frequent high
      temperatures.

PMID- 24311766
TI  - 6-Minute walk distance is an independent predictor of mortality in patients with
      idiopathic pulmonary fibrosis.
AB  - 6-min walk distance (6MWD) has recently been shown to be associated with the risk
      of mortality in patients with idiopathic pulmonary fibrosis (IPF); however, the
      independent contribution of 6MWD to the prediction of mortality risk has not been
      evaluated in a large, well-defined population of patients with IPF. A Cox
      proportional hazards model was used to characterise the relationship between risk
      factors of interest and all-cause mortality in IPF patients who completed a week
      24 study visit in a clinical trial evaluating interferon gamma-1b (n=748). Risk
      factors of interest included the independent predictors of mortality in the
      previously published clinical prediction model together with 6MWD and 24-week
      change in 6MWD. Baseline 6MWD <250 m was associated with a two-fold increase in
      the risk of mortality (hazard ratio 2.12, 95% CI 1.15-3.92) and a 24-week decline
      in 6MWD >50 m was associated with a nearly three-fold increase in mortality risk
      (hazard ratio 2.73; 95% CI 1.60-4.66). Inclusion of 6MWD data improved model
      discrimination compared with the original model (C-statistic 0.80 (95% CI 0.76
      0.85) versus 0.75 (0.71-0.79)). Both 6MWD and change in 6MWD are independent
      predictors of mortality in patients with IPF. The addition of 6MWD to the
      clinical prediction model improves model discrimination compared with the
      original model. 

PMID- 24311767
TI  - Relationship between leptin and lung function in young healthy children.

PMID- 24311768
TI  - Exercise oxygen uptake efficiency slope independently predicts poor outcome in
      pulmonary arterial hypertension.

PMID- 24311769
TI  - Does exercise test modality influence dyspnoea perception in obese patients with
      COPD?
AB  - The purpose of this study was to investigate whether differences in physiological
      responses to weight-bearing (walking) and weight-supported (cycle) exercise
      influence dyspnoea perception in obese chronic obstructive pulmonary disease
      (COPD) patients, where such discrepancies are probably exaggerated. We compared
      metabolic, ventilatory and perceptual responses during incremental treadmill and
      cycle exercise using a matched linearised rise in work rate in 18 (10 males and
      eight females) obese (mean +/- sd body mass index 36.4 +/- 5.0 kg.m(-2)) patients
      with COPD (forced expiratory volume in 1 s 60 +/- 11% predicted). Compared with
      cycle testing, treadmill testing was associated with a significantly higher
      oxygen uptake, lower ventilatory equivalent for oxygen and greater oxyhaemoglobin
      desaturation at a given work rate (p<0.01). Cycle testing was associated with a
      higher respiratory exchange ratio (p<0.01), earlier ventilatory threshold
      (p<0.01) and greater peak leg discomfort ratings (p=0.01). Ventilation, breathing
      pattern and operating lung volumes were similar between tests, as were
      dyspnoea/work rate and dyspnoea/ventilation relationships. Despite significant
      between-test differences in physiological responses, ventilation, operating lung
      volumes and dyspnoea intensity were similar at any given external power output
      during incremental walking and cycling exercise in obese COPD patients. These
      data provide evidence that either exercise modality can be selected for reliable
      evaluation of exertional dyspnoea in this population in research and clinical
      settings.

PMID- 24311770
TI  - Beyond the IFN-gamma horizon: biomarkers for immunodiagnosis of infection with
      Mycobacterium tuberculosis.
AB  - Latent infection with Mycobacterium tuberculosis (LTBI) is defined by the
      presence of M. tuberculosis-specific immunity in the absence of active
      tuberculosis. LTBI is detected using interferon-gamma release assays (IGRAs) or
      the tuberculin-skin-test (TST). In clinical practice, IGRAs and the TSTs have
      failed to distinguish between active tuberculosis and LTBI and their predictive
      value to identify individuals at risk for the future development of tuberculosis
      is limited. There is an urgent need to identify biomarkers that improve the
      clinical performance of current immunodiagnostic methods for tuberculosis
      prevention, diagnosis and treatment monitoring. Here, we review the landscape of
      potential alternative biomarkers useful for detection of infection with M.
      tuberculosis. We describe what individual markers add in terms of specificity for
      active/latent infection, prediction of progression to active tuberculosis and
      immunodiagnostic potential in high-risk groups' such as HIV-infected individuals
      and children. 

PMID- 24311772
TI  - A specific DAMP profile identifies susceptibility to smoke-induced airway
      inflammation.

PMID- 24311771
TI  - Telomere length in circulating leukocytes is associated with lung function and
      disease.
AB  - Several clinical studies suggest the involvement of premature ageing processes in
      chronic obstructive pulmonary disease (COPD). Using an epidemiological approach,
      we studied whether accelerated ageing indicated by telomere length, a marker of
      biological age, is associated with COPD and asthma, and whether intrinsic age
      related processes contribute to the interindividual variability of lung function.
      Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls
      defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD
      cases according to the Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric
      parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)
      and FEV1/FVC) of 12 595 individuals. Associations with telomere length were
      tested by linear regression, adjusting for age, sex and smoking status. We
      observed negative associations between telomere length and asthma (beta= -0.0452,
      p=0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being
      stronger and more significant when using GLI criteria than those of GOLD. In both
      diseases, effects were stronger in females than males. The investigation of
      spirometric indices showed positive associations between telomere length and FEV1
      (p=1.07*10(-7)), FVC (p=2.07*10(-5)), and FEV1/FVC (p=5.27*10(-3)). The effect
      was somewhat weaker in apparently healthy subjects than in COPD or asthma
      patients. Our results provide indirect evidence for the hypothesis that cellular
      senescence may contribute to the pathogenesis of COPD and asthma, and that lung
      function may reflect biological ageing primarily due to intrinsic processes,
      which are likely to be aggravated in lung diseases. 

PMID- 24311773
TI  - Experimental rhinovirus 16 infection in moderate asthmatics on inhaled
      corticosteroids.

PMID- 24311774
TI  - The association between public transport and active tuberculosis in Lima, Peru.

PMID- 24311775
TI  - Sputum microbiota in moderate versus severe patients with COPD.

PMID- 24311776
TI  - Treatment options in severe fungal asthma and allergic bronchopulmonary
      aspergillosis.
AB  - Severe asthma with fungal sensitisation and allergic bronchopulmonary
      aspergillosis encompass two closely related subgroups of patients with severe
      allergic asthma. Pulmonary disease is due to pronounced host inflammatory
      responses to noninvasive subclinical endobronchial infection with filamentous
      fungi, usually Aspergillus fumigatus. These patients usually do not achieve
      satisfactory disease control with conventional treatment of severe asthma, i.e.
      high-dose inhaled corticosteroids and long-acting bronchodilators. Although
      prolonged systemic corticosteroids are effective, they carry a substantial
      toxicity profile. Supplementary or alternative therapies have primarily focused
      on use of antifungal agents including oral triazoles and inhaled amphotericin B.
      Immunomodulation with omalizumab, a humanised anti-IgE monoclonal antibody, or
      "pulse" monthly high-dose intravenous corticosteroid, has also been employed.
      This article considers the experience with these approaches, with emphasis on
      recent clinical trials. 

PMID- 24311777
TI  - Genetic heterogeneity of asthma phenotypes identified by a clustering approach.
AB  - The aim of the study was to identify genetic variants associated with refined
      asthma phenotypes enabling multiple features of the disease to be taken into
      account. Latent class analysis (LCA) was applied in 3001 adults ever having
      asthma recruited in the frame of three epidemiological surveys (the European
      Community Respiratory Health Survey (ECRHS), the Swiss Study on Air Pollution and
      Lung Disease in Adults (SAPALDIA) and the Epidemiological Study on the Genetics
      and Environment of Asthma (EGEA)). 14 personal and phenotypic characteristics,
      gathered from questionnaires and clinical examination, were used. A genome-wide
      association study was conducted for each LCA-derived asthma phenotype, compared
      to subjects without asthma (n=3474). The LCA identified four adult asthma
      phenotypes, mainly characterised by disease activity, age of asthma onset and
      atopic status. Associations of genome-wide significance (p<1.25 * 10(-7)) were
      observed between "active adult-onset nonallergic asthma" and rs9851461 flanking
      CD200 (3q13.2) and between "inactive/mild nonallergic asthma" and rs2579931
      flanking GRIK2 (6q16.3). Borderline significant results (2.5 * 10(-7) < p <8.2 *
      10(-7)) were observed between three single nucleotide polymorphisms (SNPs) in the
      ALCAM region (3q13.11) and "active adult-onset nonallergic asthma". These results
      were consistent across studies. 15 SNPs identified in previous genome-wide
      association studies of asthma have been replicated with at least one asthma
      phenotype, most of them with the "active allergic asthma" phenotype. Our results
      provide evidence that a better understanding of asthma phenotypic heterogeneity
      helps to disentangle the genetic heterogeneity of asthma.

PMID- 24311778
TI  - Real-time assessment of bidirectional block during pulmonary vein cryoablation.

PMID- 24311779
TI  - The bidirectional NiFe-hydrogenase in Synechocystis sp. PCC 6803 is reduced by
      flavodoxin and ferredoxin and is essential under mixotrophic, nitrate-limiting
      conditions.
AB  - Cyanobacteria are able to use solar energy for the production of hydrogen. It is
      generally accepted that cyanobacterial NiFe-hydrogenases are reduced by NAD(P)H.
      This is in conflict with thermodynamic considerations, as the midpoint potentials
      of NAD(P)H do not suffice to support the measured hydrogen production under
      physiological conditions. We show that flavodoxin and ferredoxin directly reduce
      the bidirectional NiFe-hydrogenase of Synechocystis sp. PCC 6803 in vitro. A
      merodiploid ferredoxin-NADP reductase mutant produced correspondingly more
      photohydrogen. We furthermore found that the hydrogenase receives its electrons
      via pyruvate:flavodoxin/ferredoxin oxidoreductase (PFOR)-flavodoxin/ferredoxin
      under fermentative conditions, enabling the cells to gain ATP. These results
      strongly support that the bidirectional NiFe-hydrogenases in cyanobacteria
      function as electron sinks for low potential electrons from photosystem I and as
      a redox balancing device under fermentative conditions. However, the selective
      advantage of this enzyme is not known. No strong phenotype of mutants lacking the
      hydrogenase has been found. Because bidirectional hydrogenases are widespread in
      aquatic nutrient-rich environments that are capable of triggering phytoplankton
      blooms, we mimicked those conditions by growing cells in the presence of
      increased amounts of dissolved organic carbon and dissolved organic nitrogen.
      Under these conditions the hydrogenase was found to be essential. As these
      conditions close the two most important sinks for reduced flavodoxin/ferredoxin
      (CO2-fixation and nitrate reduction), this discovery further substantiates the
      connection between flavodoxin/ferredoxin and the NiFe-hydrogenase. 

PMID- 24311780
TI  - Designer nodal/BMP2 chimeras mimic nodal signaling, promote chondrogenesis, and
      reveal a BMP2-like structure.
AB  - Nodal, a member of the TGF-beta superfamily, plays an important role in
      vertebrate and invertebrate early development. The biochemical study of Nodal and
      its signaling pathway has been a challenge, mainly because of difficulties in
      producing the protein in sufficient quantities. We have developed a library of
      stable, chemically refoldable Nodal/BMP2 chimeric ligands (NB2 library). Three
      chimeras, named NB250, NB260, and NB264, show Nodal-like signaling properties
      including dependence on the co-receptor Cripto and activation of the Smad2
      pathway. NB250, like Nodal, alters heart looping during the establishment of
      embryonic left-right asymmetry, and both NB250 and NB260, as well as Nodal,
      induce chondrogenic differentiation of human adipose-derived stem cells. This
      Nodal-induced differentiation is shown to be more efficient than BPM2-induced
      differentiation. Interestingly, the crystal structure of NB250 shows a backbone
      scaffold similar to that of BMP2. Our results show that these chimeric ligands
      may have therapeutic implications in cartilage injuries. 

PMID- 24311781
TI  - Down-modulation of SEL1L, an unfolded protein response and endoplasmic reticulum
      associated degradation protein, sensitizes glioma stem cells to the cytotoxic
      effect of valproic acid.
AB  - Valproic acid (VPA), an histone deacetylase inhibitor, is emerging as a promising
      therapeutic agent for the treatments of gliomas by virtue of its ability to
      reactivate the expression of epigenetically silenced genes. VPA induces the
      unfolded protein response (UPR), an adaptive pathway displaying a dichotomic yin
      yang characteristic; it initially contributes in safeguarding the malignant cell
      survival, whereas long-lasting activation favors a proapoptotic response. By
      triggering UPR, VPA might tip the balance between cellular adaptation and
      programmed cell death via the deregulation of protein homeostasis and induction
      of proteotoxicity. Here we aimed to investigate the impact of proteostasis on
      glioma stem cells (GSC) using VPA treatment combined with subversion of SEL1L, a
      crucial protein involved in homeostatic pathways, cancer aggressiveness, and stem
      cell state maintenance. We investigated the global expression of GSC lines
      untreated and treated with VPA, SEL1L interference, and GSC line response to VPA
      treatment by analyzing cell viability via MTT assay, neurosphere formation, and
      endoplasmic reticulum stress/UPR-responsive proteins. Moreover, SEL1L
      immunohistochemistry was performed on primary glial tumors. The results show that
      (i) VPA affects GSC lines viability and anchorage-dependent growth by inducing
      differentiative programs and cell cycle progression, (ii) SEL1L down-modulation
      synergy enhances VPA cytotoxic effects by influencing GSCs proliferation and self
      renewal properties, and (iii) SEL1L expression is indicative of glioma
      proliferation rate, malignancy, and endoplasmic reticulum stress statuses.
      Targeting the proteostasis network in association to VPA treatment may provide an
      alternative approach to deplete GSC and improve glioma treatments. 

PMID- 24311782
TI  - Modulation of nuclear factor E2-related factor-2 (Nrf2) activation by the stress
      response gene immediate early response-3 (IER3) in colonic epithelial cells: a
      novel mechanism of cellular adaption to inflammatory stress.
AB  - Although nuclear factor E2-related factor-2 (Nrf2) protects from carcinogen
      induced tumorigenesis, underlying the rationale for using Nrf2 inducers in
      chemoprevention, this antioxidative transcription factor may also act as a proto
      oncogene. Thus, an enhanced Nrf2 activity promotes formation and chemoresistance
      of colon cancer. One mechanism causing persistent Nrf2 activation is the
      adaptation of epithelial cells to oxidative stress during chronic inflammation,
      e.g. colonocytes in inflammatory bowel diseases, and the multifunctional stress
      response gene immediate early response-3 (IER3) has a crucial role under these
      conditions. We now demonstrate that colonic tissue from Ier3(-/-) mice subject of
      dextran sodium sulfate colitis exhibit greater Nrf2 activity than Ier3(+/+) mice,
      manifesting as increased nuclear Nrf2 protein level and Nrf2 target gene
      expression. Likewise, human NCM460 colonocytes subjected to shRNA-mediated IER3
      knockdown exhibit greater Nrf2 activity compared with control cells, whereas IER3
      overexpression attenuated Nrf2 activation. IER3-deficient NCM460 cells exhibited
      reduced reactive oxygen species levels, indicating increased antioxidative
      protection, as well as lower sensitivity to TRAIL or anticancer drug-induced
      apoptosis and greater clonogenicity. Knockdown of Nrf2 expression reversed these
      IER3-dependent effects. Further, the enhancing effect of IER3 deficiency on Nrf2
      activity relates to the control of the inhibitory tyrosine kinase Fyn by the
      PI3K/Akt pathway. Thus, the PI3K inhibitor LY294002 or knockdown of Akt or Fyn
      expression abrogated the impact of IER3 deficiency on Nrf2 activity. In
      conclusion, the interference of IER3 with the PI3K/Akt-Fyn pathway represents a
      novel mechanism of Nrf2 regulation that may get lost in tumors and by which IER3
      exerts its stress-adaptive and tumor-suppressive activity. 

PMID- 24311783
TI  - MicroRNAs contribute to induced pluripotent stem cell somatic donor memory.
AB  - Induced pluripotent stem cells (iPSCs) maintain during the first few culture
      passages a set of epigenetic marks and metabolites characteristic of their
      somatic cell of origin, a concept defined as epigenetic donor memory. These
      residual somatic features are lost over time after extensive culture passaging.
      Therefore, epigenetic donor memory may be responsible for the higher
      differentiation efficiency toward the tissue of origin observed in low passage
      iPSCs versus high passage iPSC or iPSCs derived from a different tissue source.
      Remarkably, there are no studies on the relevance of microRNA (miRNA) memory
      following reprogramming, despite the established role of these molecules in the
      context of pluripotency and differentiation. Using hematopoietic progenitors
      cells as a model, we demonstrated that miRNAs play a central role in somatic
      memory retention in iPSCs. Moreover, the comparison of the miRNA expression
      profiles among iPSCs from different sources allowed for the detection of a set of
      candidate miRNAs responsible for the higher differentiation efficiency rates
      toward blood progenitors observed in low passage iPSCs. Combining bioinformatic
      predictive algorithms with biological target validation, we identified miR-155 as
      a key player for the in vitro differentiation of iPSC toward hematopoietic
      progenitors. In summary, this study reveals that during the initial passages
      following reprogramming, iPSCs maintained the expression of a miRNA set exclusive
      to the original somatic population. Hence the use of these miRNAs might hold a
      direct application toward our understanding of the differentiation process of
      iPSCs toward hematopoietic progenitor cells. 

PMID- 24311784
TI  - Inherited pain: sodium channel Nav1.7 A1632T mutation causes erythromelalgia due
      to a shift of fast inactivation.
AB  - Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain
      characterized by burning in the extremities. Inherited "paroxysmal extreme pain
      disorder" (PEPD) differs in its clinical picture and affects proximal body areas
      like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to
      mutations in the voltage-gated sodium channel Nav1.7. Electrophysiological
      characterization shows that IEM-causing mutations generally enhance activation,
      whereas mutations leading to PEPD alter fast inactivation. Previously, an A1632E
      mutation of a patient with overlapping symptoms of IEM and PEPD was reported
      (Estacion, M., Dib-Hajj, S. D., Benke, P. J., Te Morsche, R. H., Eastman, E. M.,
      Macala, L. J., Drenth, J. P., and Waxman, S. G. (2008) NaV1.7 Gain-of-function
      mutations as a continuum. A1632E displays physiological changes associated with
      erythromelalgia and paroxysmal extreme pain disorder mutations and produces
      symptoms of both disorders. J. Neurosci. 28, 11079-11088), displaying a shift of
      both activation and fast inactivation. Here, we characterize a new mutation of
      Nav1.7, A1632T, found in a patient suffering from IEM. Although transfection of
      A1632T in sensory neurons resulted in hyperexcitability and spontaneous firing of
      dorsal root ganglia (DRG) neurons, whole-cell patch clamp of transfected HEK
      cells revealed that Nav1.7 activation was unaltered by the A1632T mutation but
      that steady-state fast inactivation was shifted to more depolarized potentials.
      This is a characteristic normally attributed to PEPD-causing mutations. In
      contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow current
      decay (i.e. open-state inactivation) and did not increase resurgent currents,
      which have been suggested to contribute to high-frequency firing in physiological
      and pathological conditions. Reduced fast inactivation without increased
      resurgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation,
      A1632T. Therefore, persistent and resurgent currents are likely to determine
      whether a mutation in Nav1.7 leads to IEM or PEPD. 

PMID- 24311785
TI  - N-ethylmaleimide-sensitive factor attachment protein alpha (alphaSNAP) regulates
      matrix adhesion and integrin processing in human epithelial cells.
AB  - Integrin-based adhesion to the extracellular matrix (ECM) plays critical roles in
      controlling differentiation, survival, and motility of epithelial cells. Cells
      attach to the ECM via dynamic structures called focal adhesions (FA). FA undergo
      constant remodeling mediated by vesicle trafficking and fusion. A soluble N
      ethylmaleimide-sensitive factor (NSF) attachment protein alpha (alphaSNAP) is an
      essential mediator of membrane fusion; however, its roles in regulating ECM
      adhesion and cell motility remain unexplored. In this study, we found that siRNA
      mediated knockdown of alphaSNAP induced detachment of intestinal epithelial
      cells, whereas overexpression of alphaSNAP increased ECM adhesion and inhibited
      cell invasion. Loss of alphaSNAP impaired Golgi-dependent glycosylation and
      trafficking of beta1 integrin and decreased phosphorylation of focal adhesion
      kinase (FAK) and paxillin resulting in FA disassembly. These effects of alphaSNAP
      depletion on ECM adhesion were independent of apoptosis and NSF. In agreement
      with our previous reports that Golgi fragmentation mediates cellular effects of
      alphaSNAP knockdown, we found that either pharmacologic or genetic disruption of
      the Golgi recapitulated all the effects of alphaSNAP depletion on ECM adhesion.
      Furthermore, our data implicates beta1 integrin, FAK, and paxillin in mediating
      the observed pro-adhesive effects of alphaSNAP. These results reveal novel roles
      for alphaSNAP in regulating ECM adhesion and motility of epithelial cells. 

PMID- 24311786
TI  - The multidrug resistance IncA/C transferable plasmid encodes a novel domain
      swapped dimeric protein-disulfide isomerase.
AB  - The multidrug resistance-encoding IncA/C conjugative plasmids disseminate
      antibiotic resistance genes among clinically relevant enteric bacteria. A plasmid
      encoded disulfide isomerase is associated with conjugation. Sequence analysis of
      several IncA/C plasmids and IncA/C-related integrative and conjugative elements
      (ICE) from commensal and pathogenic bacteria identified a conserved DsbC/DsbG
      homolog (DsbP). The crystal structure of DsbP reveals an N-terminal domain, a
      linker region, and a C-terminal catalytic domain. A DsbP homodimer is formed
      through domain swapping of two DsbP N-terminal domains. The catalytic domain
      incorporates a thioredoxin-fold with characteristic CXXC and cis-Pro motifs.
      Overall, the structure and redox properties of DsbP diverge from the Escherichia
      coli DsbC and DsbG disulfide isomerases. Specifically, the V-shaped dimer of DsbP
      is inverted compared with EcDsbC and EcDsbG. In addition, the redox potential of
      DsbP (-161 mV) is more reducing than EcDsbC (-130 mV) and EcDsbG (-126 mV). Other
      catalytic properties of DsbP more closely resemble those of EcDsbG than EcDsbC.
      These catalytic differences are in part a consequence of the unusual active site
      motif of DsbP (CAVC); substitution to the EcDsbC-like (CGYC) motif converts the
      catalytic properties to those of EcDsbC. Structural comparison of the 12
      independent subunit structures of DsbP that we determined revealed that
      conformational changes in the linker region contribute to mobility of the
      catalytic domain, providing mechanistic insight into DsbP function. In summary,
      our data reveal that the conserved plasmid-encoded DsbP protein is a bona fide
      disulfide isomerase and suggest that a dedicated oxidative folding enzyme is
      important for conjugative plasmid transfer. 

PMID- 24311787
TI  - Asymmetrical Fc engineering greatly enhances antibody-dependent cellular
      cytotoxicity (ADCC) effector function and stability of the modified antibodies.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is mediated through the
      engagement of the Fc segment of antibodies with Fcgamma receptors (FcgammaRs) on
      immune cells upon binding of tumor or viral antigen. The co-crystal structure of
      FcgammaRIII in complex with Fc revealed that Fc binds to FcgammaRIII
      asymmetrically with two Fc chains contacting separate regions of the FcgammaRIII
      by utilizing different residues. To fully explore this asymmetrical nature of the
      Fc-FcgammaR interaction, we screened more than 9,000 individual clones in Fc
      heterodimer format in which different mutations were introduced at the same
      position of two Fc chains using a high throughput competition AlphaLISA(r) assay.
      To this end, we have identified a panel of novel Fc variants with significant
      binding improvement to FcgammaRIIIA (both Phe-158 and Val-158 allotypes),
      increased ADCC activity in vitro, and strong tumor growth inhibition in mice
      xenograft human tumor models. Compared with previously identified Fc variants in
      conventional IgG format, Fc heterodimers with asymmetrical mutations can achieve
      similar or superior potency in ADCC-mediated tumor cell killing and demonstrate
      improved stability in the CH2 domain. Fc heterodimers also allow more selectivity
      toward activating FcgammaRIIA than inhibitory FcgammaRIIB. Afucosylation of Fc
      variants further increases the affinity of Fc to FcgammaRIIIA, leading to much
      higher ADCC activity. The discovery of these Fc variants will potentially open up
      new opportunities of building the next generation of therapeutic antibodies with
      enhanced ADCC effector function for the treatment of cancers and infectious
      diseases. 

PMID- 24311788
TI  - Apolipoprotein A-IV reduces hepatic gluconeogenesis through nuclear receptor
      NR1D1.
AB  - We showed recently that apoA-IV improves glucose homeostasis by enhancing
      pancreatic insulin secretion in the presence of elevated levels of glucose.
      Therefore, examined whether apolipoprotein A-IV (apoA-IV) also regulates glucose
      metabolism through the suppression of hepatic gluconeogenesis. The ability of
      apoA-IV to lower gluconeogenic gene expression and glucose production was
      measured in apoA-IV(-/-) and wild-type mice and primary mouse hepatocytes. The
      transcriptional regulation of Glc-6-Pase and phosphoenolpyruvate carboxykinase
      (PEPCK) by apoA-IV was determined by luciferase activity assay. Using bacterial
      two-hybrid library screening, NR1D1 was identified as a putative apoA-IV-binding
      protein. The colocalization and interaction between apoA-IV and NR1D1 were
      confirmed by immunofluorescence, in situ proximity ligation assay, and
      coimmunoprecipitation. Enhanced recruitment of NR1D1 and activity by apoA-IV to
      Glc-6-Pase promoter was verified with ChIP and a luciferase assay. Down
      regulation of apoA-IV on gluconeogenic genes is mediated through NR1D1, as
      illustrated in cells with NR1D1 knockdown by siRNA. We found that apoA-IV
      suppresses the expression of PEPCK and Glc-6-Pase in hepatocytes; decreases
      hepatic glucose production; binds and activates nuclear receptor NR1D1 and
      stimulates NR1D1 expression; in cells lacking NR1D1, fails to inhibit PEPCK and
      Glc-6-Pase gene expression; and stimulates higher hepatic glucose production and
      higher gluconeogenic gene expression in apoA-IV(-/-) mice. We conclude that apoA
      IV inhibits hepatic gluconeogenesis by decreasing Glc-6-Pase and PEPCK gene
      expression through NR1D1. This novel regulatory pathway connects an influx of
      energy as fat from the gut (and subsequent apoA-IV secretion) with inhibition of
      hepatic glucose production. 

PMID- 24311789
TI  - Structural basis for antibody recognition in the receptor-binding domains of
      toxins A and B from Clostridium difficile.
AB  - Clostridium difficile infection is a serious and highly prevalent nosocomial
      disease in which the two large, Rho-glucosylating toxins TcdA and TcdB are the
      main virulence factors. We report for the first time crystal structures revealing
      how neutralizing and non-neutralizing single-domain antibodies (sdAbs) recognize
      the receptor-binding domains (RBDs) of TcdA and TcdB. Surprisingly, the complexes
      formed by two neutralizing antibodies recognizing TcdA do not show direct
      interference with the previously identified carbohydrate-binding sites,
      suggesting that neutralization of toxin activity may be mediated by mechanisms
      distinct from steric blockage of receptor binding. A camelid sdAb complex also
      reveals the molecular structure of the TcdB RBD for the first time, facilitating
      the crystallization of a strongly negatively charged protein fragment that has
      resisted previous attempts at crystallization and structure determination.
      Electrospray ionization mass spectrometry measurements confirm the
      stoichiometries of sdAbs observed in the crystal structures. These studies
      indicate how key epitopes in the RBDs from TcdA and TcdB are recognized by sdAbs,
      providing molecular insights into toxin structure and function and providing for
      the first time a basis for the design of highly specific toxin-specific
      therapeutic and diagnostic agents. 

PMID- 24311790
TI  - Gene trap mice reveal an essential function of dual specificity phosphatase
      Dusp16/MKP-7 in perinatal survival and regulation of Toll-like receptor (TLR)
      induced cytokine production.
AB  - MAPK activity is negatively regulated by members of the dual specificity
      phosphatase (Dusp) family, which differ in expression, substrate specificity, and
      subcellular localization. Here, we investigated the function of Dusp16/MKP-7 in
      the innate immune system. The Dusp16 isoforms A1 and B1 were inducibly expressed
      in macrophages and dendritic cells following Toll-like receptor stimulation. A
      gene trap approach was used to generate Dusp16-deficient mice. Homozygous
      Dusp16tp/tp mice developed without gross abnormalities but died perinatally.
      Fetal liver cells from Dusp16tp/tp embryos efficiently reconstituted the lymphoid
      and myeloid compartments with Dusp16-deficient hematopoietic cells. However, GM
      CSF-induced proliferation of bone marrow progenitors in vitro was impaired in the
      absence of Dusp16. In vivo challenge with Escherichia coli LPS triggered higher
      production of IL-12p40 in mice with a Dusp16-deficient immune system. In vitro,
      Dusp16-deficient macrophages, but not dendritic cells, selectively overexpressed
      a subset of TLR-induced genes, including the cytokine IL-12. Dusp16-deficient
      fibroblasts showed enhanced activation of p38 and JNK MAPKs. In macrophages,
      pharmacological inhibition and siRNA knockdown of JNK1/2 normalized IL-12p40
      secretion. Production of IL-10 and its inhibitory effect on IL-12 production were
      unaltered in Dusp16tp/tp macrophages. Altogether, the Dusp16 gene trap mouse
      model identifies an essential role in perinatal survival and reveals selective
      control of differentiation and cytokine production of myeloid cells by the MAPK
      phosphatase Dusp16. 

PMID- 24311791
TI  - Mycobacterium tuberculosis Rv2179c protein establishes a new exoribonuclease
      family with broad phylogenetic distribution.
AB  - Ribonucleases (RNases) maintain the cellular RNA pool by RNA processing and
      degradation. In many bacteria, including the human pathogen Mycobacterium
      tuberculosis (Mtb), the enzymes mediating several central RNA processing
      functions are still unknown. Here, we identify the hypothetical Mtb protein
      Rv2179c as a highly divergent exoribonuclease. Although the primary sequence of
      Rv2179c has no detectable similarity to any known RNase, the Rv2179c crystal
      structure reveals an RNase fold. Active site residues are equivalent to those in
      the DEDD family of RNases, and Rv2179c has close structural homology to
      Escherichia coli RNase T. Consistent with the DEDD fold, Rv2179c has
      exoribonuclease activity, cleaving the 3' single-strand overhangs of duplex RNA.
      Functional orthologs of Rv2179c are prevalent in actinobacteria and found in
      bacteria as phylogenetically distant as proteobacteria. Thus, Rv2179c is the
      founding member of a new, large RNase family with hundreds of members across the
      bacterial kingdom. 

PMID- 24311792
TI  - Ruling in a suspect: the role of AP2S1 mutations in familial hypocalciuric
      hypercalcemia type 3.

PMID- 24311793
TI  - Evolving paradigm for managing small nonfunctional incidentally discovered
      pancreatic neuroendocrine tumors.

PMID- 24311794
TI  - Predicting outcome in patients with thyroid cancer.

PMID- 24311801
TI  - Testing the constant-volume hypothesis by magnetic resonance imaging of Mytilus
      galloprovincialis heart.
AB  - The constant-volume (CV) hypothesis was tested using the Mytilus
      galloprovincialis heart under two conditions. The volume of the ventricle,
      auricles and pericardium, and the flow in the heart and adjacent vessels were
      measured by magnetic resonance imaging. In synthetic seawater at 23 degrees C
      (immersed condition), the end-diastolic volume (EDV), end-systolic volume (ESV)
      and stroke volume (SV) were 50%, 21% and 29% of the heart volume, respectively,
      and the auricle volume (VA) was maximized at end-systole. Assuming a constant
      volume of the heart, venous return to the auricles (IV) was constant, and out
      flow from the pericardium to the kidney (IPK) was 2/3 of SV. During aerial
      exposure (emersed condition), EDV, ESV and SV decreased to 33%, 22% and 11%,
      respectively. VA was maximized at end-diastole and associated with the decrease
      of systolic IV to 1/2 of diastolic IV, while IPK remained at 80% of the immersed
      condition. Based on these results--in addition to two postulates of the CV
      hypothesis: (1) the total volume of the heart is always the same, and (2)
      ventricle contraction causes a decrease in pressure in the pericardium--we
      modified two postulates: (3) the low pericardial pressure maintains venous return
      from the anterior oblique vein to the auricle, and (4) the pressure difference
      between the auricle and the pericardium drives haemolymph filtration through the
      auricle walls. We also added a new postulate: (5) dilatation of the ventricle is
      associated with the haemolymph output to the kidney via the renopericardial
      canals.

PMID- 24311802
TI  - Interplay between group size, huddling behavior and basal metabolism: an
      experimental approach in the social degu.
AB  - Mammals exposed to low temperatures increase their metabolic rate to maintain
      constant body temperature and thus compensate for heat loss. This high and costly
      energetic demand can be mitigated through thermoregulatory behavior such as
      social grouping or huddling, which helps to decrease metabolic rate as function
      of the numbers of individuals grouped. Sustained low temperatures in endothermic
      animals produce changes over time in rates of energy expenditure, by means of
      phenotypic plasticity. However, the putative modulating effect that huddling
      exerts on the flexibility of the basal metabolic rate (BMR) due to thermal
      acclimation remains unknown. We determined BMR values in Octodon degus, an
      endemic Chilean rodent, after being acclimated to either 15 or 30 degrees C
      during 60 days, both alone and in groups of three and five individuals. At 15
      degrees C, BMR of huddling individuals was 40% lower than that of animals housed
      alone. Moreover, infrared thermography revealed a significant increase in local
      surface temperatures in huddled animals. Furthermore, individual thermal
      conductance was lower in individuals acclimated to 15 degrees C than to 30
      degrees C, but no differences were observed between single and grouped animals.
      Our results indicate that huddling prevents an increase in BMR when animals are
      acclimated to cold conditions and that this effect is proportional to the number
      of animals grouped. 

PMID- 24311795
TI  - An aroma of complexity: how the unique genetics of aromatase (CYP19A1) explain
      diverse phenotypes from hens and hyenas to human gynecomastia, and testicular and
      other tumors.

PMID- 24311803
TI  - Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in
      Burmese python (Python bivittatus).
AB  - Physiological cardiac hypertrophy is characterized by reversible enlargement of
      cardiomyocytes and changes in chamber architecture, which increase stroke volume
      and via augmented convective oxygen transport. Cardiac hypertrophy is known to
      occur in response to repeated elevations of O2 demand and/or reduced O2 supply in
      several species of vertebrate ectotherms, including postprandial Burmese pythons
      (Python bivittatus). Recent data suggest postprandial cardiac hypertrophy in P.
      bivittatus is a facultative rather than obligatory response to digestion, though
      the triggers of this response are unknown. Here, we hypothesized that an O2
      supply-demand mismatch stimulates postprandial cardiac enlargement in Burmese
      pythons. To test this hypothesis, we rendered animals anemic prior to feeding,
      essentially halving blood oxygen content during the postprandial period. Fed
      anemic animals had heart rates 126% higher than those of fasted controls, which,
      coupled with a 71% increase in mean arterial pressure, suggests fed anemic
      animals were experiencing significantly elevated cardiac work. We found
      significant cardiac hypertrophy in fed anemic animals, which exhibited ventricles
      39% larger than those of fasted controls and 28% larger than in fed controls.
      These findings support our hypothesis that those animals with a greater magnitude
      of O2 supply-demand mismatch exhibit the largest hearts. The 'low O2 signal'
      stimulating postprandial cardiac hypertrophy is likely mediated by elevated
      ventricular wall stress associated with postprandial hemodynamics. 

PMID- 24311805
TI  - Ectoparasite performance when feeding on reproducing mammalian females: an
      unexpected decrease when on pregnant hosts.
AB  - Reproduction is an energy-demanding activity in mammalian females, with increased
      energy requirements during pregnancy and, especially, during lactation. To better
      understand the interactions between parasitism and host reproduction, we
      investigated feeding and reproductive performance of fleas (Xenopsylla ramesis)
      parasitizing non-reproducing, pregnant or lactating gerbilline rodents (Meriones
      crassus). Based on energetic considerations, we predicted that feeding and
      reproductive performance of fleas would be lowest on non-breeding females,
      moderate on pregnant females and highest on lactating females. We estimated
      feeding performance of the fleas via absolute and mass-specific bloodmeal size
      and reproductive performance via egg production and latency to peak oviposition.
      Host reproductive status had no effect on either absolute or mass-specific
      bloodmeal size or the day of peak oviposition, but significantly affected the
      daily number of eggs produced by a female flea. Surprisingly, and contrary to our
      predictions, egg production of fleas fed on pregnant rodents was significantly
      lower than that of fleas on non-reproducing and lactating rodents, while no
      difference in egg production between fleas feeding on non-reproducing and
      lactating hosts was found. Our results suggest that differences in parasite
      reproduction when feeding on hosts of different reproductive status are not
      associated with the different energy requirements of the hosts at non-breeding,
      pregnancy and lactation but rather with variation in hormonal and/or immune
      status during these periods. 

PMID- 24311804
TI  - Rhodopsin coexpression in UV photoreceptors of Aedes aegypti and Anopheles
      gambiae mosquitoes.
AB  - Differential rhodopsin gene expression within specialized R7 photoreceptor cells
      divides the retinas of Aedes aegypti and Anopheles gambiae mosquitoes into
      distinct domains. The two species express the rhodopsin orthologs Aaop8 and
      Agop8, respectively, in a large subset of these R7 photoreceptors that function
      as ultraviolet receptors. We show here that a divergent subfamily of mosquito
      rhodopsins, Aaop10 and Agop10, is coexpressed in these R7 photoreceptors. The
      properties of the A. aegypti Aaop8 and Aaop10 rhodopsins were analyzed by
      creating transgenic Drosophila expressing these rhodopsins. Electroretinogram
      recordings, and spectral analysis of head extracts, obtained from the Aaop8
      strain confirmed that Aaop8 is an ultraviolet-sensitive rhodopsin. Aaop10 was
      poorly expressed and capable of eliciting only small and slow light responses in
      Drosophila photoreceptors, and electroretinogram analysis suggested that it is a
      long-wavelength rhodopsin with a maximal sensitivity near 500 nm. Thus,
      coexpression of Aaop10 rhodopsin with Aaop8 rhodopsin has the potential to modify
      the spectral properties of mosquito ultraviolet receptors. Retention of Op10
      rhodopsin family members in the genomes of Drosophila species suggests that this
      rhodopsin family may play a conserved role in insect vision. 

PMID- 24311806
TI  - Biomechanical strategies for mitigating collision damage in insect wings:
      structural design versus embedded elastic materials.
AB  - The wings of many insects accumulate considerable wear and tear during their
      lifespan, and this irreversible structural damage can impose significant costs on
      insect flight performance and survivability. Wing wear in foraging bumblebees
      (and likely many other species) is caused by inadvertent, repeated collisions
      with vegetation during flight, suggesting the possibility that insect wings may
      display biomechanical adaptations to mitigate the damage associated with
      collisions. We used a novel experimental technique to artificially induce wing
      wear in bumblebees and yellowjacket wasps, closely related species with similar
      life histories but distinct wing morphologies. Wasps have a flexible resilin
      joint (the costal break) positioned distally along the leading edge of the wing,
      which allows the wing tip to crumple reversibly when it hits an obstacle, whereas
      bumblebees lack an analogous joint. Through experimental manipulation of its
      stiffness, we found that the costal break plays a critical role in mitigating
      collision damage in yellowjacket wings. However, bumblebee wings do not
      experience as much damage as would be expected based on their lack of a costal
      break, possibly due to differences in the spatial arrangement of supporting wing
      veins. Our results indicate that these two species utilize different wing design
      strategies for mitigating damage resulting from collisions. A simple inertial
      model of a flapping wing reveals the biomechanical constraints acting on the
      costal break, which may help explain its absence in bumblebee wings. 

PMID- 24311807
TI  - A comparative analysis of marine mammal tracheas.
AB  - In 1940, Scholander suggested that stiffened upper airways remained open and
      received air from highly compressible alveoli during marine mammal diving. There
      are few data available on the structural and functional adaptations of the marine
      mammal respiratory system. The aim of this research was to investigate the
      anatomical (gross) and structural (compliance) characteristics of excised marine
      mammal tracheas. Here, we defined different types of tracheal structures,
      categorizing pinniped tracheas by varying degrees of continuity of cartilage
      (categories 1-4) and cetacean tracheas by varying compliance values (categories
      5A and 5B). Some tracheas fell into more than one category along their length;
      for example, the harbor seal (Phoca vitulina) demonstrated complete rings
      cranially, and as the trachea progressed caudally, tracheal rings changed
      morphology. Dolphins and porpoises had less stiff, more compliant spiraling rings
      while beaked whales had very stiff, less compliant spiraling rings. The pressure
      volume (P-V) relationships of isolated tracheas from different species were
      measured to assess structural differences between species. These findings lend
      evidence for pressure-induced collapse and re-inflation of lungs, perhaps
      influencing variability in dive depth or ventilation rates of the species
      investigated. 

PMID- 24311808
TI  - Antimicrobial properties of a nanostructured eggshell from a compost-nesting
      bird.
AB  - Infection is an important source of mortality for avian embryos but parental
      behaviors and eggs themselves can provide a network of antimicrobial defenses.
      Mound builders (Aves: Megapodiidae) are unique among birds in that they produce
      heat for developing embryos not by sitting on eggs but by burying them in
      carefully tended mounds of soil and microbially decomposing vegetation. The low
      infection rate of eggs of one species in particular, the Australian brush-turkey
      (Alectura lathami), suggests that they possess strong defensive mechanisms. To
      identify some of these mechanisms, we first quantified antimicrobial albumen
      proteins and characterized eggshell structure, finding that albumen was not
      unusually antimicrobial, but that eggshell cuticle was composed of nanometer
      sized calcite spheres. Experimental tests revealed that these modified eggshells
      were significantly more hydrophobic and better at preventing bacterial attachment
      and penetration into the egg contents than chicken eggs. Our results suggest that
      these mechanisms may contribute to the antimicrobial defense system of these
      eggs, and may provide inspiration for new biomimetic anti-fouling surfaces. 

PMID- 24311809
TI  - Autonomous changes in the swimming direction of sperm in the gastropod Strombus
      luhuanus.
AB  - The sperm of the gastropod Strombus luhuanus show dimorphism. The eusperm have a
      nucleus and fertilize the egg, whereas the other type of sperm, parasperm, are
      anucleate and are thought to assist fertilization. Here we report the autonomous
      changes in the swimming pattern of S. luhuanus eusperm. In artificial seawater,
      the eusperm collected from S. luhuanus sperm ducts formed sperm bundles and
      initially swam backward with asymmetric flagellar waveforms to detach from the
      bundles. One hour later, the sperm began to swim forward and in a circle. After
      an additional 1 h incubation, the sperm swam straight, with a change in the
      flagellar waveforms from asymmetric to symmetric. Spontaneous backward swimming
      with symmetric waveforms was also observed. The eusperm stored in the female
      seminal receptacle were motile and showed forward symmetric swimming with
      spontaneous backward swimming, which appeared necessary for detachment from the
      wall of receptacle. All of these motility changes were observed in the absence of
      parasperm, suggesting that these changes autonomously occur in eusperm. Our
      waveform analysis of these swimming patterns revealed that only the swimming with
      symmetric waveform showed reverse propagation of the flagellar waveforms. Both
      types of backward swimming were diminished in Ca(2+)-free seawater and in
      seawater containing Ni(2+), indicating the regulation of swimming direction by
      Ca(2+)-dependent signal transduction. 

PMID- 24311810
TI  - Geographical differences in maternal basking behaviour and offspring growth rate
      in a climatically widespread viviparous reptile.
AB  - In reptiles, the thermal environment during embryonic development affects
      offspring phenotypic traits and potentially offspring fitness. In viviparous
      species, mothers can potentially manipulate the embryonic thermal environment
      through their basking behaviour and, thus, may be able to manipulate offspring
      phenotype and increase offspring fitness. One way in which mothers can maximise
      offspring phenotype (and thus potentially affect offspring fitness) is by fine
      tuning their basking behaviour to the environment in order to buffer the embryo
      from deleterious developmental temperatures. In widespread species, it is unclear
      whether populations that have evolved under different climatic conditions will
      exhibit different maternal behaviours and/or thermal effects on offspring
      phenotype. To test this, we provided extended or reduced basking opportunity to
      gravid spotted skinks (Niveoscincus ocellatus) and their offspring from two
      populations at the climatic extremes of the species' distribution. Gravid females
      fine-tuned their basking behaviour to the basking opportunity, which allowed them
      to buffer their embryos from potentially negative thermal effects. This fine
      tuning of female basking behaviour appears to have led to the expression of
      geographical differences in basking behaviour, with females from the cold alpine
      regions being more opportunistic in their basking behaviour than females from the
      warmer regions. However, those differences in maternal behaviour did not preclude
      the evolution of geographic differences in thermal effects: offspring growth
      varied between populations, potentially suggesting local adaptation to basking
      conditions. Our results demonstrate that maternal effects and phenotypic
      plasticity can play a significant role in allowing species to cope in changing
      environmental conditions, which is particularly relevant in the context of
      climate change. 

PMID- 24311811
TI  - Adult fruit fly attraction to larvae biases experience and mediates social
      learning.
AB  - We investigated whether adult fruit flies (Drosophila melanogaster) use cues of
      larvae as social information in their food patch choice decisions. Adult male and
      female fruit flies showed attraction to odours emanating from foraging larvae,
      and females preferred to lay eggs on food patches occupied by larvae over similar
      unoccupied patches. Females learned and subsequently preferred to lay eggs at
      patches with novel flavours previously associated with feeding larvae over
      patches with novel flavours previously associated with no larvae. However, when
      we controlled for the duration of exposure to each flavoured patch, females no
      longer preferred the flavour previously associated with feeding larvae. This
      suggests that social learning in this context is indirect, as a result of strong
      social attraction biasing experience. 

PMID- 24311812
TI  - Biomechanical consequences of epiphytism in intertidal macroalgae.
AB  - Epiphytic algae grow on other algae rather than hard substrata, perhaps
      circumventing competition for space in marine ecosystems. Aquatic epiphytes are
      widely thought to negatively affect host fitness; it is also possible that
      epiphytes benefit from associating with hosts. This study explored the
      biomechanical costs and benefits of the epiphytic association between the
      intertidal brown algal epiphyte Soranthera ulvoidea and its red algal host
      Odonthalia floccosa. Drag on epiphytized and unepiphytized hosts was measured in
      a recirculating water flume. A typical epiphyte load increased drag on hosts by
      ~50%, increasing dislodgment risk of epiphytized hosts compared with hosts that
      did not have epiphytes. However, epiphytes were more likely to dislodge from
      hosts than hosts were to dislodge from the substratum, suggesting that drag added
      by epiphytes may not be mechanically harmful to hosts if epiphytes break first.
      Concomitantly, epiphytes experienced reduced flow when attached to hosts, perhaps
      allowing them to grow larger or live in more wave-exposed areas. Biomechanical
      interactions between algal epiphytes and hosts are complex and not necessarily
      negative, which may partially explain the evolution and persistence of epiphytic
      relationships. 

PMID- 24311813
TI  - The effects of naris occlusion on mouse nasal turbinate development.
AB  - Unilateral naris occlusion, a standard method for causing odor deprivation, also
      alters airflow on both sides of the nasal cavity. We reasoned that manipulating
      airflow by occlusion could affect nasal turbinate development given the
      ubiquitous role of environmental stimuli in ontogenesis. To test this hypothesis,
      newborn mice received unilateral occlusion or sham surgery and were allowed to
      reach adulthood. Morphological measurements were then made of paraffin sections
      of the whole nasal cavity. Occlusion significantly affected the size, shape and
      position of turbinates. In particular, the nasoturbinate, the focus of our
      quantitative analysis, had a more delicate appearance on the occluded side
      relative to the open side. Occlusion also caused an increase in the width of the
      dorsal meatus within the non-occluded and occluded nasal fossae, compared with
      controls, and the position of most turbinates was altered. These results suggest
      that a mechanical stimulus from respiratory airflow is necessary for the normal
      morphological development of turbinates. To explore this idea, we estimated the
      mechanical forces on turbinates caused by airflow during normal respiration that
      would be absent as a result of occlusion. Magnetic resonance imaging scans were
      used to construct a three-dimensional model of the mouse nasal cavity that
      provided the input for a computational fluid dynamics simulation of nasal
      airflow. The simulation revealed maximum shear stress values for the walls of
      turbinates in the 1 Pa range, a magnitude that causes remodeling in other
      biological tissues. These observations raise the intriguing possibility that
      nasal turbinates develop partly under the control of respiratory mechanical
      forces. 

PMID- 24311814
TI  - Daphnia's dilemma: adjustment of carbon budgets in the face of food and
      cholesterol limitation.
AB  - We studied the carbon (C) metabolism in Daphnia when the amount of C (food
      quantity) and/or the content of biochemical nutrients (food quality) was
      limiting. Growth performances and C budgets of Daphnia magna (assimilation,
      faeces egestion, excretion and respiration measured by [(14)C]-tracing) were
      analysed when animals were raised on different food quantities and concentrations
      of cholesterol, an essential biochemical food compound. Cholesterol is of special
      interest because it not only acts as limiting nutrient but also contributes to
      the overall C pool of the animals. As the tissue cholesterol concentration in
      Daphnia is quite low, we hypothesized the selective exclusion of cholesterol from
      C budgeting and tested this using radiolabelled cholesterol. Somatic growth rates
      of D. magna were highest at high quantity and quality and were reduced to a
      moderate value if either the food quantity or the cholesterol concentration was
      low. Growth was lowest at low food quantity and quality. The measurements of C
      budgets revealed high regulative response to low food quality at high food
      quantity only. Here, low dietary cholesterol caused bulk C assimilation
      efficiency (AE) to decrease and assimilated (excess) C to be increasingly
      respired. Additionally, Daphnia enhanced efficient adjustment of C budgets when
      facing cholesterol limitation by (1) increasing the AE of the cholesterol itself
      and (2) not changing cholesterol respiration, which was still not detectable. In
      contrast, at low food quantity, Daphnia is unable to adjust for low food quality,
      emphasizing that food limitation could overrule food quality effects. 

PMID- 24311815
TI  - Calcium uptake in aquatic insects: influences of phylogeny and metals (Cd and
      Zn).
AB  - Calcium sequestration in the hypo-osmotic freshwater environment is imperative in
      maintaining calcium homeostasis in freshwater aquatic organisms. This uptake
      process is reported to have the unintended consequence of potentially toxic heavy
      metal (Cd, Zn) uptake in a variety of aquatic species. However, calcium uptake
      remains poorly understood in aquatic insects, the dominant invertebrate faunal
      group in most freshwater ecosystems. Here, we examined Ca uptake and interactions
      with heavy metals (Cd, Zn) at low ambient Ca levels (12.5 MUmol l(-1)) in 12
      aquatic insect species within Ephemerellidae (mayfly) and Hydropsychidae
      (caddisfly), two families differentially responsive to trace metal pollution. We
      found Ca uptake varied 70-fold across the 12 species studied. Body mass and clade
      (family) were found to significantly influence both Ca uptake and adsorption
      (P<=0.05). Zn and Cd uptake rate constants (ku) exhibited a strong correlation
      (r=0.96, P<0.0001), suggesting a shared transport system. Ca uptake failed to
      significantly correlate with either Zn or Cd ku values. Further, neither Zn nor
      Cd exhibited inhibitory effects toward Ca uptake. In fact, we saw evidence of
      modest stimulation of Ca uptake rates in some metal treatments. This work
      suggests that insects generally differ from other freshwater taxa in that aqueous
      Ca uptake does not appear to be compromised by Cd or Zn exposure. It is important
      to understand the trace metal and major ion physiology of aquatic insects because
      of their ecological importance and widespread use as ecological indicators. 

PMID- 24311816
TI  - Decreased hydrogen peroxide production and mitochondrial respiration in skeletal
      muscle but not cardiac muscle of the green-striped burrowing frog, a natural
      model of muscle disuse.
AB  - Suppression of disuse-induced muscle atrophy has been associated with altered
      mitochondrial reactive oxygen species (ROS) production in mammals. However,
      despite extended hindlimb immobility, aestivating animals exhibit little skeletal
      muscle atrophy compared with artificially immobilised mammalian models.
      Therefore, we studied mitochondrial respiration and ROS (H2O2) production in
      permeabilised muscle fibres of the green-striped burrowing frog, Cyclorana
      alboguttata. Mitochondrial respiration within saponin-permeabilised skeletal and
      cardiac muscle fibres was measured concurrently with ROS production using high
      resolution respirometry coupled to custom-made fluorometers. After 4 months of
      aestivation, C. alboguttata had significantly depressed whole-body metabolism by
      ~70% relative to control (active) frogs, and mitochondrial respiration in saponin
      permeabilised skeletal muscle fibres decreased by almost 50% both in the absence
      of ADP and during oxidative phosphorylation. Mitochondrial ROS production showed
      up to an 88% depression in aestivating skeletal muscle when malate, succinate and
      pyruvate were present at concentrations likely to reflect those in vivo. The
      percentage ROS released per O2 molecule consumed was also ~94% less at these
      concentrations, indicating an intrinsic difference in ROS production capacities
      during aestivation. We also examined mitochondrial respiration and ROS production
      in permeabilised cardiac muscle fibres and found that aestivating frogs
      maintained respiratory flux and ROS production at control levels. These results
      show that aestivating C. alboguttata has the capacity to independently regulate
      mitochondrial function in skeletal and cardiac muscles. Furthermore, this work
      indicates that ROS production can be suppressed in the disused skeletal muscle of
      aestivating frogs, which may in turn protect against potential oxidative damage
      and preserve skeletal muscle structure during aestivation and following arousal. 

PMID- 24311817
TI  - Are torpid bats immune to anthropogenic noise?
AB  - Anthropogenic noise has a negative impact on a variety of animals. However, many
      bat species roost in places with high levels of anthropogenic noise. Here, we
      tested the hypothesis that torpid bats are insensitive to anthropogenic noise. In
      a laboratory experiment, we recorded skin temperature (Tsk) of bats roosting
      individually that were subjected to playbacks of different types of noise. We
      found that torpid bats with Tsk ~10 degrees C lower than their active Tsk
      responded to all types of noise by elevating Tsk. Bats responded most strongly to
      colony and vegetation noise, and most weakly to traffic noise. The time of day
      when torpid bats were exposed to noise had a pronounced effect on responses.
      Torpid bats showed increasing responses from morning towards evening, i.e.
      towards the onset of the active phase. Skin temperature at the onset of noise
      exposure (Tsk,start, 17-29 degrees C) was not related to the response. Moreover,
      we found evidence that torpid bats rapidly habituated to repeated and prolonged
      noise exposure. 

PMID- 24311818
TI  - Suspended sediment prolongs larval development in a coral reef fish.
AB  - Increasing sediment input into coastal environments is having a profound
      influence on shallow marine habitats and associated species. Coral reef
      ecosystems appear to be particularly sensitive, with increased sediment
      deposition and re-suspension being associated with declines in the abundance and
      diversity of coral reef fishes. While recent research has demonstrated that
      suspended sediment can have negative impacts on post-settlement coral reef
      fishes, its effect on larval development has not been investigated. In this
      study, we tested the effects of different levels of suspended sediment on larval
      growth and development time in Amphiprion percula, a coral reef damselfish.
      Larvae were subjected to four experimental concentrations of suspended sediment
      spanning the range found around coastal coral reefs (0-45 mg l(-1)). Larval
      duration was significantly longer in all sediment treatments (12 days) compared
      with the average larval duration in the control treatment (11 days).
      Approximately 75% of the fish in the control had settled by day 11, compared with
      only 40-46% among the sediment treatments. In the highest sediment treatment,
      some individuals had a larval duration twice that of the median duration in the
      control treatment. Unexpectedly, in the low sediment treatment, fish at
      settlement were significantly longer and heavier compared with fish in the other
      treatments, suggesting delayed development was independent of individual
      condition. A sediment-induced extension of the pelagic larval stage could
      significantly reduce numbers of larvae competent to settle and, in turn, have
      major effects on adult population dynamics. 

PMID- 24311819
TI  - Root pressure and beyond: energetically uphill water transport into xylem
      vessels?
AB  - The thermodynamics of root pressure remains an enigma up to the present day.
      Water is transported radially into xylem vessels, under some conditions even when
      the xylem sap is more dilute than the ambient medium (soil solution). It is
      suggested here that water secretion across the plasma membrane of xylem
      parenchyma cells is driven by a co-transport of water and solutes as previously
      shown for mammalian epithelia (Zeuthen T. 2010. Water-transporting proteins.
      Journal of Membrane Biology 234, 57-73.). This process could drive volume flow
      'energetically uphill', against the free energy gradient of water. According to
      the model, solutes released by xylem parenchyma cells are subsequently retrieved
      from the sap at the expense of metabolic energy to maintain the concentration
      gradient that drives the water secretion. Transporters of the CCC type known to
      mediate water secretion in mammalian cells have also been found in Arabidopsis
      and in rice. The mechanism proposed here for root pressure could also explain
      refilling of embolized vessels. Moreover, it could contribute to long-distance
      water transport in trees when the cohesion-tension mechanism of water ascent
      fails. This is discussed with respect to the old and the more recent literature
      on these subjects. 

PMID- 24311820
TI  - Cultural Variation in Implicit Mental Illness Stigma.
AB  - Culture shapes how individuals perceive and respond to others with mental
      illness. Prior studies have suggested that Asians and Asian Americans typically
      endorse greater stigma of mental illness compared to Westerners (White Europeans
      and Americans). However, whether these differences in stigma arise from cultural
      variations in automatic affective reactions or deliberative concerns of the
      appropriateness of one's reactions to mental illness remains unknown. Here we
      compared implicit and explicit attitudes toward mental illness among Asian and
      Caucasian Americans. Asian Americans showed stronger negative implicit attitudes
      toward mental illness relative to Caucasian Americans, suggesting that cultural
      variation in stigma of mental illness can be observed even when concerns
      regarding the validity and appropriateness of one's attitudes toward mental
      illness are minimized. Asian Americans also explicitly endorsed greater desire
      for social distance from mental illness relative to Caucasian Americans. These
      findings suggest that cultural variations in mental illness stigma may arise from
      cultural differences in automatic reactions to mental illness, though cultural
      variations in deliberative processing may further shape differences in these
      immediate reactions to mental illness.

PMID- 24311821
TI  - Drug Generations in the 2000s: An Analysis of Arrestee Data.
AB  - Much empirical evidence indicates that the popularity of various drugs tends to
      increase and wane over time producing episodic epidemics of particular drugs.
      These epidemics mostly affect persons reaching their late teens at the time of
      the epidemic resulting in distinct drug generations. This article examines the
      drug generations present in the 2000s among arrestees in the 10 locations served
      by the Arrestee Drug Abuse Monitoring-II program. At all 10 locations, our
      findings show that crack use is still common among older arrestees but not among
      arrestees born more recently. Marijuana is the drug most common among younger
      arrestees. The article also examines trends in heroin, methamphetamine, and
      powder cocaine use among arrestees at the few locations where their use was
      substantial.

PMID- 24311822
TI  - Multiracial faces: How categorization affects memory at the boundaries of race.
AB  - Monoracial and multiracial individuals are likely to have different
      conceptualizations of race and subsequently different approaches towards racial
      ambiguity. In particular, monoracial individuals may be more likely to rely on
      categories when processing ambiguous faces, whereas multiracial individuals may
      tend to ignore such categorizations due to a reduced tendency to essentialize
      race. We compared monoracial (White and Asian) and biracial (Asian/White)
      individuals' memory patterns. Specifically, we examined participants' memory for
      White, Asian, and biracial faces labeled as either White or Asian. Both White and
      Asian participants relied on the labels, remembering faces labeled as the in
      group better than faces labeled as the out-group. Biracial participants relied
      less on the labels, exhibiting better recognition memory overall. Biracial
      participants' memory performance was also highly correlated with a less
      essentialist view of human traits. This cognitive flexibility may serve an
      adaptive function for biracial individuals and contribute to enhanced facial
      recognition.

PMID- 24311823
TI  - New ligand platforms featuring boron-rich clusters as organomimetic substituents.
AB  - 200 years of research with carbon-rich molecules have shaped the development of
      modern chemistry. Research pertaining to the chemistry of boron-rich species has
      historically trailed behind its more distinguished neighbor (carbon) in the
      periodic table. Notably, a potentially rich and, in many cases, unmatched field
      of coordination chemistry using boronrich clusters remains fundamentally
      underdeveloped. Our work has been devoted to examining several basic concepts
      related to the functionalization of icosahedral boron-rich clusters and their use
      as ligands, aimed at designing fundamentally new hybrid molecular motifs and
      materials. Particularly interesting are icosahedral carboranes, which can be
      regarded as 3D analogs of benzene. These species comprise a class of boron-rich
      clusters that were discovered in the 1950s during the "space race" while
      researchers were developing energetic materials for rocket fuels. Ultimately, the
      unique chemical and physical properties of carborane species, such as rigidity,
      indefinite stability to air and moisture, and 3D aromaticity, may allow one to
      access a set of properties not normally available in carbon-based chemistry.
      While technically these species are considered as inorganic clusters, the
      chemical properties they possess make these boron-rich species suitable for
      replacing and/or altering structural and functional features of the organic and
      organometallic molecules-a phenomenon best described as "organomimetic". Aside
      from purely fundamental features associated with the organomimetic chemistry of
      icosahedral carboranes, their use can also provide new avenues in the development
      of systems relevant to solving current problems associated with energy
      production, storage, and conversion.

PMID- 24311824
TI  - Do as You're Told! Facets of Agreeableness and Early Adult Outcomes for Inner
      City Boys.
AB  - With data from the middle cohort of the Pittsburgh Youth Study, a prospective
      longitudinal study of inner-city boys, we examined whether Big Five agreeableness
      facets could be reliably recovered in this sample, and whether facets predicted
      educational, occupational, social, and antisocial life outcomes assessed a decade
      later. Caregivers described their adolescent boys' personalities using the Common
      California Q-Set; twelve years later, participants were interviewed and court
      records were obtained. Factor analyses recovered two facets: compliance and
      compassion. Compliance predicted more schooling and lower risk of unemployment,
      teenage fatherhood, and crime; compassion related to longer committed
      relationships. Findings highlight the value of studying personality at the facet
      level.

PMID- 24311825
TI  - Effective Strategies for Maintaining Research Participation in Clinical Trials.
AB  - Achieving high protocol adherence is essential for ensuring the overall success
      and scientific merit of clinical trials. Strategies for maximizing recruitment
      and treatment adherence have been previously explored in the literature. There
      has been less focus, however, on effective methods for maintaining participants
      in research follow-up. This article examines factors associated with poor follow
      up rates as well as strategies for facilitating research commitment and
      addressing sources of nonadherence. Special attention is devoted to alcohol- and
      substance-dependent populations, groups known to have poor adherence rates.
      Examples are drawn from the COMBINE Study, an NIAAA-funded, nationwide,
      multisite, combined behavioral and pharmacotherapy trial for alcohol problems
      that achieved high one-year follow-up rates. The important role of coordinating
      centers in facilitating research retention is also discussed.

PMID- 24311826
TI  - Some citation-related characteristics of scientific journals published in
      individual countries.
AB  - Relationships between publication language, impact factors and self-citations of
      journals published in individual countries, eight from Europe and one from South
      America (Brazil), are analyzed using bibliometric data from Thomson Reuters JCR
      Science Edition databases of ISI Web of Knowledge. It was found that: (1) English
      language journals, as a rule, have higher impact factors than non-English
      language journals, (2) all countries investigated in this study have journals
      with very high self-citations but the proportion of journals with high self
      citations with reference to the total number of journals published in different
      countries varies enormously, (3) there are relatively high percentages of low
      self-citations in high subject-category journals published in English as well as
      non-English journals but national-language journals have higher self-citations
      than English-language journals, and (4) irrespective of the publication language,
      journals devoted to very specialized scientific disciplines, such as electrical
      and electronic engineering, metallurgy, environmental engineering, surgery,
      general and internal medicine, pharmacology and pharmacy, gynecology, entomology
      and multidisciplinary engineering, have high self-citations.

PMID- 24311827
TI  - A study of diffusion in poly(ethyleneglycol)-gelatin based semi-interpenetrating
      networks for use in wound healing.
AB  - Semi-interpenetrating networks (sIPNs) designed to mimic extracellular matrix via
      covalent crosslinking of poly(ethylene glycol) diacrylate in the presence of
      gelatin have been shown to aid in wound healing, particularly when loaded with
      soluble factors. Ideal systems for tissue repair permit an effective release of
      therapeutic agents and flow of nutrients to proliferating cells. Appropriate
      network characterization can, consequently, be used to convey an understanding of
      the mass transfer kinetics necessary for materials to aid in the wound healing
      process. Solute transport from and through sIPNs has not yet been thoroughly
      evaluated. In the current study, the diffusivity of growth factors and nutrients
      through the polymeric system was determined. Transport of keratinocyte growth
      factor was modeled by treating the sIPN as a plane sheet into which the protein
      was loaded. The diffusion coefficient was determined to be 4.86 * 10-9 +/- 1.86 *
      10-12 cm2/s. Glucose transport was modeled as flow through a semi-permeable
      membrane. Using lag-time analysis, the diffusion coefficient was calculated to be
      2.25 * 10-6 +/- 1.98 * 10-7 cm2/s. The results were evaluated in conjunction with
      previous studies on controlled drug release from sIPNs. As expected from Einstein
      Stokes equation, diffusivity decreased as molecular size increased. The results
      offer insight into the structure-function design paradigm and show that release
      from the polymeric system is diffusion controlled, rather than dissolution
      controlled.

PMID- 24311828
TI  - Wu-Ling-San formula prophylaxis against recurrent calcium oxalate nephrolithiasis
      - a prospective randomized controlled trial.
AB  - Wu-Ling-San (WLS) formula has been proved to prevent calcium oxalate
      nephrolithiasis both in vitro and in vivo. This is the first prospective,
      randomized and placebo-controlled clinical trial of WLS in calcium oxalate
      nephrolithiasis prevention. All patients who enrolled were asked to drink enough
      fluid to urinate at least 2 L daily during the study period. A 24-hour urine
      collection was performed to establish the baseline levels of multiple urinary
      parameters before taking the medicine. The patients were randomized and divided
      into two groups. The medication group took 2 gm WLS formula three times daily for
      1 month. The control group took 2 gm placebo three times daily for 1 month. A 24
      hour urine collection was performed to evaluate multiple urinary and serum
      parameters from all patients during the study period. A total of 39 patients were
      enrolled and 28 patients completed the study. Fourteen patients were allocated to
      WLS group and 14 patients to placebo group. After treatment, the mean urine
      output level increased to 2796.4 +/- 525.7 ml/day (percentage of change, 13.9 %)
      in the WLS formula group. With placebo therapy, the mean decreased slightly to
      2521.4 +/- 762.7ml/day (percentage of change, -5.7 %). The percentage of change
      was significantly different between the two groups (independent t-test, P=0.02).
      No patient complained of side effects, such as fatigue, dizziness,
      musculoskeletal symptoms, or gastrointestinal disturbance. WLS formula is a
      promising adjunct to surgical and medical management of kidney stones. Active
      therapy with WLS formula has a positive effect on diuresis without leading to
      electrolyte imbalance. 

PMID- 24311829
TI  - The role and place of medicinal plants in the strategies for disease prevention.
AB  - Medicinal plants have been used in healthcare since time immemorial. Studies have
      been carried out globally to verify their efficacy and some of the findings have
      led to the production of plant-based medicines. The global market value of
      medicinal plant products exceeds $100 billion per annum. This paper discusses the
      role, contributions and usefulness of medicinal plants in tackling the diseases
      of public health importance, with particular emphasis on the current strategic
      approaches to disease prevention. A comparison is drawn between the 'whole
      population' and 'high-risk' strategies. The usefulness of the common-factor
      approach as a method of engaging other health promoters in propagating the ideals
      of medicinal plants is highlighted. The place of medicinal plants in preventing
      common diseases is further examined under the five core principles of the Primary
      Health Care (PHC) approach. Medicinal plants play vital roles in disease
      prevention and their promotion and use fit into all existing prevention
      strategies. However, conscious efforts need to be made to properly identify,
      recognise and position medicinal plants in the design and implementation of these
      strategies. These approaches present interesting and emerging perspectives in the
      field of medicinal plants. Recommendations are proposed for strategising the
      future role and place for medicinal plants in disease prevention. 

PMID- 24311830
TI  - Effects of methanolic extract of Moringa oleifera leaves on semen and biochemical
      parameters in cryptorchid rats.
AB  - While anti-oxidant effects of Moringa oleifera in much oxidative stress related
      diseases have been well reported, cryptorchidism on the other hand has been shown
      to cause oxidative stress. However, study is scanty on the likely role of Moringa
      oleifera in reducing cryptorchidism-induced oxidative stress in rats has not been
      studied. The present study looked into the effects of methanolic extract of
      Moringa oleifera leaves (MEMO) on semen and biochemical parameters in cryptorchid
      rats. Twenty male albino rats (200-250 g) were randomly divided into 4 groups
      (n=5 each). Groups A and B were sham-operated and treated with corn-oil and 200
      mg/kg of MEMO respectively, while groups C and D were rendered cryptorchid and
      also treated with corn-oil and 200 mg/kg of MEMO respectively. Cryptorchid rats
      had lower testicular weight, sperm count, germ cell count, testicular superoxide
      dismutase (SOD) concentration, testicular total protein and higher testicular
      malondialdehyde (MDA) concentration compared to sham-operated rats. MEMO had no
      significant effect on testicular weight and MDA concentration, while it
      significantly increased sperm count, germ cell count, testicular SOD and total
      protein in the cryptorchid rats. The present study suggests that MEMO ameliorates
      cryptorchidism associated germ cell loss and oxidative stress.

PMID- 24311831
TI  - Acute effects of aqueous leaf extract of Aspilia africana C.D. Adams on some
      haematological parameters in rats.
AB  - Several medicinal plants have been documented for their haematological effects
      either at low or high concentration but very little is known about Aspilia
      africana. The aim of the study was to investigate the acute effects of aqueous
      leaf extract of Aspilia africana at different concentrations on some
      haematological parameters in rats. Following 14 days of oral administration of
      aqueous extract of A. africana, Haematocrit (HCT), Haemoglobin concentration
      (HB), Mean Cell Haemoglobin Concentration (MCHC), Red Blood Cell Count (RBC
      Count), Total White Blood Cell Count (Total WBC Count), Absolute Neutrophils
      count (NEUT#), Absolute Lymphocytes count (LYM#), Absolute Eosinophils Count
      (EOSIN#) and Absolute Monocytes (MONO#) were evaluated in twenty (20) male Wistar
      albino rats. The rats weighed 174 +/- 20 g, and were randomly assigned into 4
      groups viz: Group 1, Control; Group 2, 250 mg/Kg/d aqueous extract; Group 3, 500
      mg/Kg/d aqueous extract; and Group 4, 750 mg/Kg/d aqueous extract. HCT, HB, MCHC,
      RBC Count, Total WBC Count, NEUT#, LYM#, EOSIN# and MONO# were significantly
      increased (P<0.001) in 500 mg/Kg/d of A. africana extract (61.13 +/- 1.65%, 13.5
      +/- 1.29 g/dl, 23.33 +/- 0.0.02 g/dl, 3.68 +/- 0.02 X 10(12)Cells/l, 2.33 +/-
      0.02 X 10(9)Cells/l, 1.32 +/- 0.04 X 10(9)Cells/l, 1.43 +/- 0.05 X 10(9)Cells/l,
      0.47 +/- 0.02 X 10(9)Cells/l and 0.47 +/- 0.04 X 10(9)Cells/l, respectively) when
      compared to the Control (51.13 +/- 0.85%, 9.56 +/- 0.43 g/dl, 19.22 +/- 0.19
      g/dl, 2.69 +/- 0.01 X 10(12)Cells/l, 1.79 +/- 0.01 X 10(9)Cells/l, 0.80 +/- 0.00
      X 10(9)Cells/l, 0.83 +/- 0.00 X 10(9)Cells/l, 0.18 +/- 0.00 X 10(9)Cells/l and
      0.24 +/- 0.00 X 10(9)Cells/l, respectively) which received no extract at all. The
      500 mg/Kg of A. africana extract proved to be the most effective, while the 750
      mg/Kg proved to be the least effective in comparison with the control. The
      results of this study further strengthened the earlier works on the medicinal
      benefits of Aspilia africana and its virtue as a good pharmacological source of
      haematopoiesis.

PMID- 24311832
TI  - Effect of fractionated extracts and isolated pure compounds of Spondias mombin
      (L. Anacardiaceae) leaves on novelty-induced rearing and grooming behaviours in
      mice.
AB  - This study attempted to elucidate the neurotransmitter systems involved in the
      neurophysiological properties of ethanolic extract, fractions and pure isolates
      of Spondias mombin leaves in mice (n = 6) after intraperitoneal (i.p.) route of
      administration.The crude ethanolic extract of Spondian mombin leaves was
      fractionated using the partitioning method to obtain the ethylacetate, butanolic
      and aqueous fractions. Open column chromatographic fractionation of the
      ethylacetate fraction yielded seven sub-fractions, out of which the pure
      coumaroyl, quercetin and gallic acid derivatives were obtained after purification
      on Sephadex LH 20. The ethanolic extract, butanolic fraction, ethylacetate
      subfractions and pure isolates of the Spondian mombin leaves were tested on
      novelty-induced rearing and grooming behaviours in mice with standard
      pharmacological tools using the open field method. The extract and its fractions
      decreased novelty-induced rearing in a dose-dependent manner. While the Coumaroyl
      derivative had no effect on novelty-induced rearing, it significantly reversed
      the inhibitory effect of yohimbine, propranolol and haloperidol on novelty
      induced rearing. Quercetin significantly potentiated the inhibitory effect of
      yohimbine on novelty-induced rearing. Naloxone significantly potentiated the
      quercetin-induced suppression of novelty-induced rearing. Gallic acid derivative
      significantly potentiated the inhibitory effect of yohimbine on novelty-induced
      rearing. Naloxone, atropine and haloperidol pretreatments significantly
      potentiated gallic acid derivative-induced suppression of novelty-induced
      rearing.The extract and its fractions had biphasic effect on novelty-induced
      grooming in mice. Coumaroyl derivative significantly increased novelty-induced
      grooming, while quercetin and gallic acid derivative decreased novelty-induced
      grooming significantly. The three pure isolates significantly reversed the
      effects of yohimbine and atropine on the novelty-induced grooming in mice.
      Propranolol-induced increase in novelty-induced grooming was significantly
      reversed by coumaroyl and gallic acid derivatives. Pre-treatment with naloxone
      significantly increased the gallic acid derivative-induced suppression of novelty
      induced grooming. Pre-treatment with haloperidol reversed the effect of coumaroyl
      derivative and potentiated the inhibitory effect of quercetin derivative and
      gallic acid derivative significantly. This study suggested that adrenergic and
      dopaminergic neuro-transmissions are strongly involved in the neural mechanisms
      of the effect of the three pure isolates derivative, while opioid neuro
      transmission is strongly linked with the neural mechanism of behavioural effect
      of coumaroyl derivative. 

PMID- 24311833
TI  - A study on anticancer activity of Caulis Spatholobi extract on human osteosarcoma
      Saos-2 cells.
AB  - The objective of the present study was to investigate the anticancer activity of
      Chinese medicine Caulis Spatholobi extract on multicentric osteosarcoma cells.
      Ultraviolet spectrophotometry was used to determine the total flavonoid content
      in each sample; vanillin sulphuric acid assay was used to determine the condensed
      tannin content in each sample; and the varying degrees of inhibitory activities
      of ethanol, ethyl acetate and n-butanol extracts of Caulis Spatholobi on human
      osteosarcoma Saos-2 cells were studied. The results showed that the inhibitory
      activity of ethyl acetate extract was the highest among the four extracts. The
      condensed tannin contents of 1.2 mg/mL Caulis Spatholobi water extract, ethanol
      extract, ethyl acetate extract and petroleum ether extract were 26.23%, 48.36%,
      70.18% and 40.51% respectively; and condensed tannin content of 1.5 mg/mL Caulis
      Spatholobi water extract, ethanol extract, ethyl acetate extract and petroleum
      ether extract were 4.15%, 5.81%, 8.76% and 7.30% respectively. 

PMID- 24311834
TI  - Antioxidant and SGC-7901 cell inhibition activities of Rhizoma Dioscoreae
      bulbiferae. ethanol extracts.
AB  - The objective of this research was to study the pharmacology of Dioscorea
      bulbifera L. on antioxidant and anticancer activity. Alcohol extracts of
      Dioscorea bulbifera L. were made out by different concentration alcohol; they
      were tested by Hydroxyl radical scavenging test, reducing capacity test and total
      antioxidant capacity test. In the anticancer test, MTT test was used to study the
      inhibition rate. The results told that 70% ethanol extracts could scavenge most
      DPPH. at 2 mg/ml. The rate was 55.2%; 80% ethanol extract could clear the most
      .OH. The clearance rate was 51.2%. 80% ethanol crude extracts possessed the
      strongest reducing ability per gram of the extract equal to 49.3 umol Fe(2 +).
      Different concentrations of the extracts could inhibit the proliferation of line
      SGC-7901, and with the concentration increased, the inhibition rate was gradually
      increased.

PMID- 24311835
TI  - Synergistic antiosteoporotic effect of Lepidium sativum and alendronate in
      glucocorticoid-induced osteoporosis in Wistar rats.
AB  - Alendronate belongs to a class of drugs called bisphosphonates. Bisphosphonates
      (BP) therapy is a vital option to reduce the risk of bone fracture in people who
      suffer from osteoporosis. Yet, bisphosphonate have displayed several side
      effects. Lepidium sativum (LS) seeds have been used in traditional folk medicine
      to heal fractured bones. However, there is a dearth of information on the impact
      of LS on bone metabolism especially in cases of glucocorticoids induced
      osteoporosis. Therefore, the aim of the study was to compare the biochemical bone
      markers and histological responses of LS alone (6 g of LS seeds in diet daily,
      n=8), ALD (alendronate, 70 mg/kg s.c.; n=8) alone, or LS and ALD combined in a
      rat model of glucocorticoid-induced osteoporosis (GIO) by injecting rats with
      methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin,
      phosphorus (P), bone-specific alkaline phosphatase (b-ALP), and tartrate
      resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO.
      GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO
      group also showed significantly decreased serum P and unaltered Ca
      concentrations. Histological examination of GIO-group tibia bones indicated an
      osteoporotic change and a concomitant decrease in percentage of trabecular area
      or bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with
      either LS and/or ALD ameliorated the above mentioned changes with variable
      degrees, with a net results of enhanced serum calcium, bone architecture, PTB, b
      ALP and decreased TRAP in LS and LS+ALD groups compared to that of animals
      treated with alendronate alone. In conclusion, our findings present evidence
      supporting the potential benefits of LS in reducing the burden of GCs on bone
      health. 

PMID- 24311836
TI  - Anti-inflammatory, cytotoxic and antioxidant effects of methanolic extracts of
      Drypetes sepiaria (Euphorbiaceae).
AB  - The aim of this study was to investigate in vitro antioxidant, anti-inflammatory
      and cytotoxic activities of the petroleum ether, ethyl acetate, methanol and
      aqueous extracts obtained from leaves of Drypetes sepiaria (Euphorbiaceae). Total
      phenolic and flavonoid contents of these crude extracts were determined as gallic
      acid and quercetin equivalents, respectively. In in vitro antioxidant method,
      methanol extract exhibited higher free radical scavenging activity compared to
      standard compound, ascorbic acid with IC50 of 95.43 ug/ml (DPPH) and 67.05 ug/ml
      (ABTS). Methanol extract was able to inhibit inflammation by in vitro about 85
      90% (HRBC stabilization method) and in vivo about 40-45% (Paw oedema method) anti
      inflammatory assays compared to standard produced 50.04% at 6 h period. In
      cytotoxicity assay (MTT assay) methanolic extract exhibited IC50 of 10 ug/ml. In
      apoptosis (flow cytometric assay), the control group showed normal caspase 3
      activity in the SiHa cells which was 0.24%, and increased up to 40% after
      treatment.

PMID- 24311837
TI  - In vitro anti-oxidative activities of the various parts of Parkia biglobosa and
      GC-MS analysis of extracts with high activity.
AB  - The anti-oxidative activities of sequentially extracted solvent fractions of
      different parts of P. biglobosa were evaluated in a series of in vitro assays.
      Our findings indicated that all extracts had electron donating and free radical
      scavenging activities. But the ethanol (EtOH) extracts from all the parts
      demonstrated more promising anti-oxidative effects in these experimental models.
      Apart from the aqueous extracts of the stem bark and leaves, all other extracts
      exhibited hydroxyl radical scavenging (HRS) activity but the ethyl acetate
      (EtOAc) extract of the stem bark and EtOH extracts of the root and leaves
      possessed more powerful HRS activity than other corresponding extracts in the
      parts. Further, nitric oxide (NO) inhibition activities were observed in all the
      extracts except the EtOAc extract of the stem bark which showed pro-oxidative
      activity. However, the EtOH extract of the stem bark and root as well as the
      EtOAc extract of the leaves displayed more potent anti-NO activity than other
      extracts in the parts. The GC-MS analysis of the EtOH extracts revealed that the
      most abundant phytochemicals are pyrogallol derivatives. Data from this study
      suggest that the EtOH extracts from different parts of P. biglobosa contained
      potent anti-oxidative agents and pyrogallol could be the main bioactive
      constituent. 

PMID- 24311838
TI  - In vitro assessment of antioxidant, phytochemical and nutritional properties of
      extracts from the leaves of Ocimum gratissimum (Linn).
AB  - The antioxidant, phytochemical and nutritional properties of acetone, methanol
      and aqueous extracts of the leaves of Ocimum gratissimum (Linn) were investigated
      to evaluate the therapeutic and nutritional potential of the leaves of this
      plant. The antioxidant of the plant extracts were assessed against 1,1-Diphenyl-2
      picrylhydrazyl (DPPH) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)
      diammonium salt (ABTS) and ferric reducing agent. Total phenolics, flavonoids,
      flavonols and proanthocyanidins were determined to assess their corresponding
      effect on the antioxidant activity of this plant. The extracts exhibited DPPH and
      ABTS(.+) radical scavenging activities, which was comparable to butylated
      hydroxytoluene (BHT). The phytochemical screening revealed the presence of
      alkaloids, tannins, saponin, steroids, cardiacglycoside, flavonoid, terpenoids
      and phenol. The proximate analysis confirms that the leaves contain appreciable
      amount of ash, crude protein, lipids, fibre and carbohydrates. The macro and
      micro elements and constituents revealed that the leaves contain significant
      amount of sodium, potassium, calcium, magnesium, iron, zinc, phosphorus, copper,
      nitrogen, and manganese. This study shows that the leaf can be used as a
      therapeutic agent and justifies its application in folkloric medicine.

PMID- 24311839
TI  - Anti cancerous efficacy of Ayurvedic milk extract of Semecarpus anacardium nuts
      on hepatocellular carcinoma in Wistar rats.
AB  - The objective of the study was to determine the anticancerous efficacy of
      Ayurvedic preparation made of Semecarpus anacardium (SA) nuts. Five groups of
      rats were used for the study. Group I served as water control. Hepatocellular
      carcinoma (HCC) was induced in groups II, III and IV animals using N
      nitrosodiethylamine as inducing agent followed by phenobarbitone as promoter for
      13 weeks. Group-II animals were kept untreated as hepatocellular carcinoma
      control. Group-III animals were treated with Ayurvedic milk extract of Semecarpus
      anacardium nuts at dose mentioned in Ashtangahridaya, an authentic book of
      Ayurveda for 49 days and group-IV animals were treated with doxorubicin as
      reference drug at dose of 1mg/kg twice a week for 7 weeks. Group V animals were
      kept as drug (SA nut milk extract) control for studying the effect of nut milk
      extract on normal rats. After 154 days of experiment, all animals were subjected
      to screening for HCC by estimation of liver enzymes, HCC marker (alpha-2
      macroglobulin) and histopathology. Both liver enzymes and HCC marker were
      increased in hepatocellular carcinoma control along with neoplastic changes in
      liver and were decreased in Semecarpus anacardium nut milk extract treated group.
      The Ayurvedic drug showed positive correlation with the action of doxorubicin.
      This study demonstrated the efficacy of Semecarpus anacardium nut milk extract
      for the treatment of hepatocellular carcinoma either alone or along with
      chemotherapy. 

PMID- 24311840
TI  - Antimicrobial activities of some Euphorbia species.
AB  - In this study, the antimicrobial activities of methanolic extracts and latex of
      some Euphorbia species used for medical purposes in Turkey were investigated. The
      extracts of Euphorbia aleppica L., Euphorbia szovitsii Fisch.&Mey. var.
      harputensis Aznav. ex M. S. Khan, Euphorbia falcata L. sub. falcata var. falcata,
      Euphorbia denticulata Lam., Euphorbia macroclada Boiss., Euphorbia cheiradenia
      Boiss.&Hohen, Euphorbia virgata Waldst.&Kit., Euphorbia petiolata Banks&Sol. were
      prepared with methanol. The antimicrobial activities of these extracts were
      examined on test microorganisms as follows: Staphylococcus aureus COWAN 1,
      Bacillus megaterium DSM 32, Proteus vulgaris FMC 1, Klebsiella pneumonia FMC 5,
      Escherichia coli ATCC 25922, Pseudomonas aeruginosa DSM 50071, Candida albicans
      FMC 17, Candida glabrata ATCC 66032, Epidermophyton sp. and Trichophyton sp. by
      the disc diffusion methods and well agar method. The MIC values of extracts were
      determined according to the broth microdulitions method. Results indicated that
      extracts of Euphorbia species inhibited the growth of tested microorganisms in
      the different ratio. Also, the MIC values of extracts were determined as 31,2
      1000 ug. 

PMID- 24311841
TI  - A study on the protective effect of Silybum marianum extract on hepatic ischemia
      reperfusion injury.
AB  - The objective of the study was to study the protective effect of Silybum marianum
      extract on hepatic ischemia-reperfusion injury. Rats were randomly divided into
      five groups; namely Silybum marianum extract high-, medium-, and low-dose
      protection groups, model group and control group. Hepatic ischemia-reperfusion
      injury model was prepared. Serum or plasma AST, ALT, MDA, TNF-alpha, IL-1beta, IL
      6 levels were measured. The results revealed that after liver injury, AST, ALT,
      MDA, TNF-alpha, IL-1beta, and IL-6 levels significantly increased in succession,
      showing significant differences. We concluded that inflammatory cytokines
      participate in liver injury and that Silybum marianum extract can reduce the
      production of inflammatory cytokines, and thus can have a protective effect on
      hepatic ischemia and reperfusion. 

PMID- 24311842
TI  - A study on the extraction process of active ingredients from Akebia Stem and an
      analysis of their anti-gastric cancer activity.
AB  - The study investigated the extraction process of active ingredients from akebia
      stem and an analysis of their anti-gastric cancer activity. Three different
      extraction methods were used to obtain extracts, namely the decoction method
      (group A), reflux extraction method (group B), and maceration method (group C),
      of which reflux extraction method and maceration method used ethanol as the
      extraction solvent, while decoction method used distilled water for extraction.
      The differences in anti-gastric cancer activity of the three extracts were
      compared. MTT assay was used to test and compare the inhibitory effects of
      extracts obtained in A, B, and C groups on gastric cancer cells. The results
      showed that the dry extract obtained by heat reflux extraction with "water
      ethanol" ratio of 1:2, extractant volume of 70 ml, with ethanol as extraction
      solvent presented the best inhibitory activity on gastric cancer SGC-7901 cells
      in this study. Its inhibitory effect did not change over time, and was directly
      proportional to the concentration. 

PMID- 24311843
TI  - A study on inhibitory effect of Spica prunellae extract on T lymphoma cell EL-4
      tumour.
AB  - The objective of the study was to investigate the in-vivo anti-tumour activity of
      Spica prunellae extract, and to preliminarily explore the possible mechanism of
      in-vivo anti-tumour effect of Spica prunellae extract. Tumour inhibition rate and
      tumour apoptosis-related protein status were determined using the mice model of
      transplanted T lymphoma cell EL-4 tumour, and by immunohistochemical method. The
      results revealed that Spica prunellae extract showed certain tumour inhibitory
      effect, and compared with the model group. Tumour weight in Spica prunellae high
      dose group was highly significantly different (P<0.01). Tumour weight in Spica
      prunellae medium-dose group was also significantly different (P<0.05) compared
      with the model group. Spica prunellae high-dose group enabled the high expression
      of Bcl-2 protein (47.54%) and low expression of Bax protein (13.14%). The study
      concluded that Spica prunellae extract has certain in vivo anti-tumour effect,
      which may be achieved through regulation of apoptosis related proteins. 

PMID- 24311844
TI  - Gongronema latifolium delays gastric emptying of semi-solid meals in diabetic
      dogs.
AB  - The aim of the study was to investigate sonographically the effect of Gongronema
      latifolium on gastric emptying of semi-solid meals in diabetic dogs. Twenty-five
      alloxan-induced diabetic dogs were randomly allotted into five groups of five
      dogs each in a randomised placebo-controlled study. These are placebo, prokinetic
      dose, low dose, moderate dose and high dose groups. The placebo group served as
      the control. The low, moderate and high dose groups ingested methanolic leaf
      extract of G. latifolium at 100 mg/kg, 250 mg/kg, 500 mg/kg respectively, while
      the prokinetic group ingested 0.5 mg/kg of metoclopramide. After a 12-hour fast,
      each group ingested its treatment capsules 30 minutes before the administration
      of test meal. Measurements of gastric emptying and blood glucose levels were
      obtained from each dog 30 minutes before and immediately after the ingestion of a
      test meal, every 15 minutes for another 4 hours and then every 30 minutes for
      further 2 hours. Gastric emptying of the moderate and high dose groups were 227.8
      +/- 9.9 min and 261.3 +/- 19.3 min respectively and significantly (p < 0.0001)
      slower than the placebo control group of 143.0 +/- 17.8 min. The gastric emptying
      of the low dose group (169.8 +/- 3.8) and control group did not differ
      significantly (p > 0.05). A strong inverse relationship between gastric emptying
      and the incremental blood glucose levels was noted in the diabetic dogs after the
      ingestion of Gongronema latifolium (r = -0.90; p < 0.0001). Gonogronema
      latifolium delayed gastric emptying in diabetic dogs.

PMID- 24311845
TI  - Nigella sativa concoction induced sustained seroreversion in HIV patient.
AB  - Nigella sativa had been documented to possess many therapeutic functions in
      medicine but the least expected is sero-reversion in HIV infection which is very
      rare despite extensive therapy with highly active anti-retroviral therapy
      (HAART). This case presentation is to highlight the complete recovery and sero
      reversion of adult HIV patient after treatment with Nigella sativa concoction for
      the period of six months. The patient presented to the herbal therapist with
      history of chronic fever, diarrhoea, weight loss and multiple papular pruritic
      lesions of 3 months duration. Examination revealed moderate weight loss, and the
      laboratory tests of ELISA (Genscreen) and western blot (new blot 1 & 2) confirmed
      sero-positivity to HIV infection with pre-treatment viral (HIV-RNA) load and CD4
      count of 27,000 copies/ml and CD4 count of 250 cells/ mm(3) respectively. The
      patient was commenced on Nigella sativa concoction 10 mls twice daily for 6
      months.. He was contacted daily to monitor side-effects and drug efficacy. Fever,
      diarrhoea and multiple pruritic lesions disappeared on 5th, 7th and 20th day
      respectively on Nigella sativa therapy. The CD4 count decreased to 160 cells/ mm3
      despite significant reduction in viral load (<=1000 copies/ml) on 30th day on N.
      sativa. Repeated EIA and Western blot tests on 187th day on Nigella sativa
      therapy was sero-negative. The post therapy CD4 count was 650 cells/ mm(3) with
      undetectable viral (HIV-RNA) load. Several repeats of the HIV tests remained sero
      negative, aviraemia and normal CD4 count since 24 months without herbal therapy.
      This case report reflects the fact that there are possible therapeutic agents in
      Nigella sativa that may effectively control HIV infection.

PMID- 24311846
TI  - A study on the inhibitory effect of Radix Semiaquilegiae extract on human
      hepatoma HEPG-2 and SMMC-7721 cells.
AB  - The main objective of this paper was to investigate the extraction process of
      ethanol extract of Radix Semiaquilegiae, as well as its inhibitory activity on
      human hepatoma HepG-2 and SMMC-7721 cells, and to compare the inhibitory effects
      of different concentrations of ethanol extracts against these two hepatoma cells.
      Ethanol reflux extraction and ultrasound-assisted extraction with ethanol at room
      temperature were used in the extraction process, and MTT assay was mainly used in
      the activity experiment to perform in-vitro anti HepG-2 and SMMC-7721 cell
      activity screening of ethanol extract, and to calculate the cell inhibition rates
      of the extracts. The results showed that among the two types of extracts, ethanol
      reflux extract had more superior antitumour activity to that of the ultrasonic
      extract, but all of the extracts obtained had certain anti-cancer activities, and
      the anti-proliferative activity increased with the increase of concentration. 

PMID- 24311847
TI  - Anti-bacterial activities and phytochemical screening of extracts of different
      parts of Thalictrum rhynchocarpum.
AB  - Parts of the plant Thalictrum rhyncocarpum are used in herbal medicine in Kenya
      to treat various infections. The aim of this study was to evaluate in-vitro anti
      bacteria activities and phytochemical profiles of solvent extracts of the leaves,
      stem bark and root of Thalictrum rhyncocarpum against Bacillus subtilis-6633,
      Staphylococcus aures-SG 511, Escherichia coli SG 458, Pseudomonus aeruginosa
      K799/61 and Mycobacterium vaccae-10670. Anti-bacterial activity tests were
      carried out using disc diffusion assay and tube dilution technique, and
      phytochemical screening was carried out through Thin Layer Chromatography. The
      crude extracts showed antibacterial effects on M. vaccae, P. aeruginosa and B.
      subtilis. M. vaccae was most sensitive, particularly to the methanol root
      extract. Phytochemical screening of the extracts suggested the presence of
      glycosides and alkaloids in the stem bark and root extracts, and flavonoids and
      triterpenes in the leaf extracts. The study showed interesting levels of
      activities of solvent extracts of different parts of T. rhyncocarpum against some
      of the bacteria tested (M. vaccae, P. aeruginosa and B. subtilis). The results
      provide some scientific rationale for the traditional use of the plant in Kenya
      to treat different microbial infections. 

PMID- 24311848
TI  - A study on anti-tumour effect of Solanum lyratum Thunb. extract in S180 tumour
      bearing mice.
AB  - The objective of the study was to investigate the anti-tumour effect of ethanol
      extract of Solanum lyratum Thunb. in S180 tumour-bearing mice, and to
      preliminarily explore its mechanism of action. METHODS: Mice were made into S180
      solid tumour model, grouped and administered. Tumour inhibition rate was measured
      by harvesting the tumours. Serum IL-2, TNF-a contents were measured by taking
      blood samples, and thymus index and spleen index were measured by harvesting the
      thymus and spleen. The results showed that the Solanum lyratum Thunb. extract had
      certain tumour inhibitory effect, which can elevate the serum IL-2, TNF-a
      contents, and increase the thymus and spleen indices to a certain extent. The
      study concluded that Solanum lyratum Thunb. extract has certain in vivo anti
      tumour effect which may be exerted through enhancing the body immunity.

PMID- 24311849
TI  - Effects of ethanol extract of Radix Sophorae Flavescentis on activity of colon
      cancer HT29 cells.
AB  - This paper mainly studied the inhibitory effect of total ethanol extract of Radix
      Sophorae Flavescentis on proliferation of colon cancer HT29 cells. By reflux
      extraction method and with ethanol as extraction solvent, different extracts were
      obtained at different ethanol concentrations, different solid-liquid ratios, and
      at different times. And their inhibitory activities against HT29 cells were
      compared using MTT assay. The experimental results showed that the extraction
      processes under three conditions can all draw relatively high inhibition rates.
      The optimum ethanol extraction process conditions were as follows: a solid-liquid
      ratio of 1:9, 80 min of heat reflux extraction with 95% ethanol. 

PMID- 24311850
TI  - Managing ulcerative colitis by increasing hydrogen production via oral
      administration of Acarbose.
AB  - The objective of the study was to investigate ulcerative colitis management
      through oral administration of acarbose. Acarbose has gained importance as a drug
      used widely to treat Diabetes Mellitus Type 2,as it acts on the small intestine
      by competitively inhibiting enzymes that delay the release of glucose from
      complex carbohydrates, thereby specifically reducing postprandial glucose
      excursion. The main side-effect of treatment with Acarbose, flatulence, occurs
      when undigested carbohydrates are fermented by colonic bacteria, resulting in
      considerable amounts of hydrogen. We found that the enteric benefits of Acarbose
      are partly due to be their ability to neutralise oxidative stress via increased
      production of H2 in the gastrointestinal tract. Therefore, some symptoms of
      ulcerative colitis in human beings can be ameliorated by Acarbose.

PMID- 24311851
TI  - Tongue diagnosis of traditional Chinese medicine for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with unknown
      aetiology that causes the immune system to attack the joints (synoviums), leading
      to chronic inflammation. According to the traditional Chinese medicine (TCM), RA
      falls into the category of Impediment disease ("Bi" syndrome), that is, poor
      circulation of qi and blood (stasis). Tongue diagnosis is an important method of
      TCM to detect blood stasis. In this study, 74 RA patients, meeting the pre-set
      criteria, were recruited via rheumatology outpatient clinic and examined by
      experienced rheumatology physicians. Two images-one of the tongue and the other,
      sublingual vessels-of the same patient were taken by a Canon digital camera in a
      darkroom with uniform lighting conditions. Relevant features of the tongue were
      extracted by utilising image processing techniques. Every tongue was classified
      into corresponding patterns based on the features identified. The subjects
      included 62 females and 12 males with an average age of 49.86 +/- 13.81 years
      old, an average morbidity period of 4.56 +/- 3.92 years, an average rheumatoid
      factor (RF) of 225.3 +/- 373.8 IU/mL and an average erythrocyte sedimentation
      rate of (ESR) 40.9 +/- 31.9 m/hr. According to our study, 86% of the patients
      with RA have tongues with sublingual vessels with a width of more than 2.7 mm, a
      length of more than 3/5 from tongue tipto sublingual caruncle, or a count of
      sublingual vessels more than 2. Moreover, since RA index is highly correlated
      with blood stasis in TCM, a logistic regression is conducted to predict the
      probability of presence of RA using RF and ESR as explanatory variables. Also,
      the logistic regression analysis of RA with respect to the conventional tongue
      diagnosis criteria was performed. Based on the aforementioned studies, we
      concluded that tongue diagnosis is helpful in detecting blood stasis of RA.

PMID- 24311852
TI  - Simultaneous determination of contents of three active components in Jiejia
      tincture by HPLC method.
AB  - The objective of the study was to determine the contents of three active
      components in Jiejia tincture by establishing HPLC method. Test articles were
      prepared by ultrasonic extraction. Separation was performed using a Kromasil C18
      (250 mm * 4.6 mm, 5 um) chromatographic column, and gradient elution was
      performed with acetonitrile-0.3% phosphoric acid solution as the mobile phase at
      a volumetric flow rate of 0.80 mL/min. The contents of catechin, baicalin and
      berberine in Jiejia tincture were determined at the wavelength of 276 nm and a
      column temperature of 30 ?. The results revealed that catechin showed a good
      linear relationship at the range of 100~800 ug/mL (r=0.9997); baicalin showed a
      good linear relationship at the range of 15~120 ug/mL (r=0.9996), and berberine
      at the range of 7~56 ug/mL (r=0.9995). Their average recovery rates were 99.67%
      (RSD 1.01%, n=6), 98.7% (RSD 1.93%, n=6) and 100.5% (RSD 2.88%, n=6)
      respectively. The study concluded that the high-performance liquid chromatography
      established in this study was simple, accurate and reproducible, and can also be
      used in the determination of catechin, baicalin and berberine contents in Jiejia
      tincture. 

PMID- 24311853
TI  - On the inhibitory effect of Drynaria fortunei extract on human myeloma SP20
      cells.
AB  - The objective of the study was to investigate the inhibitory effect of Drynaria
      fortunei extract on human myeloma SP2 cells. Three different total extracts of
      Drynaria fortunei were obtained by reflux extraction method using different
      organic solvents including ethanol, methanol and petroleum ether. Their
      anticancer activities on SP20 cells were tested, and the maximum inhibition rate
      was obtained. The inhibitory effects on tumour cells at 12 h, 24 h, 36 h and 48 h
      were tested, and the inhibition curves at different time periods were plotted.
      The results showed that the methanol and ethanol extracts have similar inhibition
      rates at 24 h, which are around 55%. On the other hand, the maximum inhibition
      rate of petroleum ether extract is only 36% within 24 h. Moreover, within the
      time periods of 36 h and 48 h, its inhibition rates are all below 10%.

PMID- 24311854
TI  - Study on anti-Ehrlich ascites tumour effect of Pinellia ternata polysaccharide in
      vivo.
AB  - The objectives of the study were to investigate the anti-tumour activity of
      Pinellia ternata polysaccharide in vivo, and to preliminarily explore the
      possible mechanism of its antitumour action. Mouse model of Ehrlich ascites
      tumour (solid tumour) was used to detect the serum SOD, MDA and GSH-Px levels in
      mouse and to measure the tumour inhibition rate and survival prolongation rate.
      The results showed that Pinellia ternata polysaccharide had some tumour
      inhibitory effect. Tumour weight of Pinellia ternata polysaccharide high-dose
      group was highly significantly different (P<0.01) compared with the model group.
      Tumour weight between Pinellia ternata polysaccharide medium-dose group and model
      group also had a significant difference (P<0.05). Moreover, in the Pinellia
      ternata polysaccharide high-dose group, survival prolongation rate of ascites
      tumour mice reached 62.23%, and mouse serum SOD, MDA and GSH-Px levels also rose
      in varying degrees. The study concluded that Pinellia ternata polysaccharide
      extract had some in vivo anti-tumour effects, which were probably associated with
      the enhancement of the body's ability to scavenge excess free radicals by
      improving the body's enzyme activity. 

PMID- 24311855
TI  - Antihyperglycaemic and antioxidant effects of Adenia lobata Engl.
      (Passifloraceae) in streptozotocin-induced diabetic rats.
AB  - The antihyperglycaemic and antioxidant activities of a Ghanaian medicinal plant
      namely Adenia lobata Engl (Passifloraceae), used to treat diabetes mellitus in
      traditional medicine, was investigated. The dried stem powder of A. lobata was
      successively extracted by Soxhlet with petroleum ether and 70% ethanol to obtain
      the crude petroleum ether (PEAL: yield =1.1 w/w %) and ethanol (EEAL: yield = 5.4
      w/w %) extracts. The extracts were assessed for their antihyperglycaemic and
      antioxidant activities. The antihyperglycaemic activity of PEAL and EEAL were
      determined in streptozotocin-induced diabetic rats (70 mg/kg body weight). Five
      groups of diabetic rats were given 150, 300 and 600 mg/kg body weight of PEAL and
      EEAL orally once daily for 20 days. Glibenclamide (5 mg/kg body weight) was used
      as positive control while distilled water (5 ml) acted as the normal diabetic
      control. The blood glucose levels were monitored initially for 6 hours and
      subsequently over 24 days. Both extracts exhibited statistically significant (p<
      0.001) antihyperglycaemic activity throughout the study period, with EEAL showing
      the greatest activity. The antioxidant properties of the petroleum ether and
      ethanol extracts of A. lobata (PEAL and EEAL) were evaluated using five assays;
      total phenolic content, total antioxidant capacity, reducing power, DPPH
      scavenging effect and lipid peroxidation activity. In all these assays, the
      antioxidant properties increased with increasing concentration of the extracts.

PMID- 24311856
TI  - Anti-ulcerogenic activity of the methanol root bark extract of Cochlospermum
      planchonii (Hook f).
AB  - Cochlospermum planchonii (Hook f) is a common medicinal plant used in Nigeria
      traditional medicine for treatment of different ailments including ulcers. The
      anti ulcer activity of the root bark methanol extract of Cochlospermum planchonii
      was evaluated using different [ethanol, acetylsalicylic acid (aspirin),
      cold/restraint stress and pyloric ligation/histamine - induced ulcers and acid
      production] ulcerogenic models in rats at the doses of 250, 500, and 1000 mg/kg
      body weight using cimetidine (100 mg/kg) as a standard reference drug. The
      different doses of the extract and the reference drug significantly (p < 0.01)
      decreased all the ulcer parameters in a dose dependent manner in all the models
      used. The total number of ulcers were significantly (p < 0.05) decreased. The
      ulcer index was significantly (p < 0.004) reduced by the extract. Similarly, the
      percentage ulcer preventive index was also increased from 0% in the negative
      control up to 93.2% at the dose of 1000 mg/kg, while the percentage ulcer
      severity was dose dependently reduced by the extract. Furthermore, the extract
      significantly (p < 0.02) decreased free gastric HCl and total gastric acid. In
      conclusion, Cochlospermum planchonii methanolic root bark extract showed
      significant antiulcer activity in this study which may be as a result of its
      cytoprotective, antioxidant or antisecretory properties. 

PMID- 24311857
TI  - A study on hypoglycaemic health care function of Stigma maydis polysaccharides.
AB  - The objective of this paper was to study the therapeutic effect of Stigma maydis
      polysaccharides in diabetic mice. Mouse models of types 1 and 2 diabetes were
      established. The body weight, food intake, water intake as well as blood sugar
      level and glucose tolerance of mice were measured. Stigma maydis polysaccharides
      can improve the symptoms of weight loss and polydipsia in diabetic mice, and had
      an obvious antagonistic effect on alloxan-induced hyperglycaemia. The glucose
      tolerance test also showed that the Stigma maydis polysaccharides had very good
      effects on suppression and prevention of acute hyperglycaemia. Stigma maydis
      polysaccharides have some improvement effect on alloxan-induced types 1 and 2
      diabetes. 

PMID- 24311858
TI  - Antihyperglycaemic and antinociceptive activity evaluation of methanolic extract
      of whole plant of Amaranthus tricolour L. (Amaranthaceae).
AB  - Amaranthus tricolor whole plants are used by folk medicinal practitioners of
      Bangladesh for treatment of pain, anaemia, dysentery, skin diseases, diabetes,
      and as a blood purifier. Thus far, no scientific studies have evaluated the
      antihyperglycaemic and antinociceptive effects of the plant. The present study
      was carried out to evaluate the possible glucose tolerance efficacy of methanolic
      extracts of A. tricolour whole plants using glucose-induced hyperglycaemic mice,
      and antinociceptive effects with acetic acid-induced gastric pain models in mice.
      In antihyperglycaemic activity tests, the extract at different doses was
      administered one hour prior to glucose administration and blood glucose level was
      measured after two hours of glucose administration (p.o.) using glucose oxidase
      method. The statistical data indicated the significant oral hypoglycaemic
      activity on glucose-loaded mice at all doses of the extracts tested. Maximum
      antihyperglycaemic activity was shown at 400 mg extract per kg body weight, which
      was comparable to that of a standard drug, glibenclamide (10 mg/kg body weight).
      In antinociceptive activity tests, the extract also demonstrated a dose-dependent
      significant reduction in the number of writhings induced in mice through
      intraperitoneal administration of acetic acid. Maximum antinociceptive activity
      was observed at a dose of 400 mg extract per kg body weight, which compared
      favourably with that of a standard antinociceptive drug, aspirin, when
      administered at a dose of 200 mg per kg body weight. The results validate the
      folk medicinal use of the plant for reduction of blood sugar in diabetic patients
      as well as the folk medicinal use for alleviation of pain. The results suggest
      that this plant may possess further potential for scientific studies leading to
      possible discovery of efficacious antihyperglycaemic and antinociceptive
      components.

PMID- 24311859
TI  - A checklist of the flora of Shanjan protected area, East Azerbaijan Province, NW
      Iran.
AB  - The flora of protected Shanjan rangeland in Shabestar district, Azerbaijan
      Province, NW Iran was studied using a 1 m * 1 m quadrate in spring and summer
      2011. The climate of this area is cold and dry. In this area 94 plant species
      belonging to 25 families were identified as constituting the major part of the
      vegetation. The families in the area are Amaryllidaceae, Boraginaceae,
      Campanulaceae, Caryophllaceae, Cistaceae, Compositea, Cruciferae, Cyperaceae,
      Dipesaceae, Euphorbiaceae, Geraniaceae, Hypericaceae, Linaceae, Melvaceae,
      Orobachaceae, Papaveraceae, Paronychiaceae, Plantaginaceae, Polygolaceae,
      Ranunculaceae, Resedaceae, Rubiaceae, Scrophulariaceae, Solanaceae and
      Valerianacea. Floristic composition is Irano-Turanian elements. Detailed analysis
      showed that Biennial plants were 3.19%, Annual 41.49% and Perennial 55.32%.

PMID- 24311860
TI  - A study on the effect of aqueous extract of Lobelia chinensis on colon
      precancerous lesions in rats.
AB  - This paper studies the effects of Lobelia chinensis on colon precancerous lesions
      and on colonic epithelial proliferation and apoptosis in DMH-induced rats. After
      two weeks of feeding, 50 Wistar rats were randomly divided into five groups,
      namely the normal group, model group, Lobelia chinensis low-dose group, medium
      dose group and high-dose group. Lobelia chinensis was made into ACF model, and
      administered to experimental groups for 10 consecutive weeks. Control group was
      given equivalent amount of normal saline. After feeding for 10 weeks, the rats in
      each group were sacrificed and the changes in colonic ACF number of rats in
      experimental groups were observed, and the inhibition rates were calculated. The
      results showed that among the rats fed for 24 h and 48 h, the number of apoptotic
      cells in colonic crypts of rats in DMH group did not differ significantly from
      the control group, while the difference was obvious between the control group and
      Lobelia chinensis treatment groups. The medium and high doses, that is, 0.45 g/kg
      and 1.35 g/kg can significantly inhibit ACF formation (P<0.01). The inhibition
      rates of low, medium and high doses were 8.12%, 59.42% and 65.44%, respectively. 

PMID- 24311861
TI  - Validated modified Lycopodium spore method development for standardisation of
      ingredients of an ayurvedic powdered formulation Shatavaryadi churna.
AB  - Validated modified lycopodium spore method has been developed for simple and
      rapid quantification of herbal powdered drugs. Lycopodium spore method was
      performed on ingredients of Shatavaryadi churna, an ayurvedic formulation used as
      immunomodulator, galactagogue, aphrodisiac and rejuvenator. Estimation of
      diagnostic characters of each ingredient of Shatavaryadi churna individually was
      carried out. Microscopic determination, counting of identifying number,
      measurement of area, length and breadth of identifying characters were performed
      using Leica DMLS-2 microscope. The method was validated for intraday precision,
      linearity, specificity, repeatability, accuracy and system suitability,
      respectively. The method is simple, precise, sensitive, and accurate, and can be
      used for routine standardisation of raw materials of herbal drugs. This method
      gives the ratio of individual ingredients in the powdered drug so that any
      adulteration of genuine drug with its adulterant can be found out. The method
      shows very good linearity value between 0.988-0.999 for number of identifying
      character and area of identifying character. Percentage purity of the sample drug
      can be determined by using the linear equation of standard genuine drug. 

PMID- 24311862
TI  - Favourable culture conditions for mycelial growth of Hydnum repandum, a medicinal
      mushroom.
AB  - In this study, factors such as pH, temperature, carbon and nitrogen sources that
      affect mycelial growth of Hydnum repandum, a medicinal mushroom, were
      investigated. Different inoculum media for vegetative inoculum production were
      also examined. The best suitable pH for mycelial growth was found to be 5.5.
      Among constant temperatures, the best mycelial growth was obtained at 20 and 25
      degrees C. The mycelial growth drastically decreased at 15 degrees C, and no
      mycelia were obtained at 30 degrees C. Glucose and mannitol were found to be the
      most suitable carbon sources. Ca(NO3)2 as a nitrogen source gave the best results
      for mycelial growth. The poorest mycelial growth was noted in sucrose and xylose
      as carbon sources and in NH4NO3 and (NH4)2HPO4 as nitrogen sources. Peat and
      peat: vermiculite mixtures (1:4, 1:6, 1:8 and 1:10, v:v) were the best media to
      use in producing the vegetative inoculum of H. repandum. 

PMID- 24311863
TI  - A study on the inhibitory effect of matrine on gastric cancer SGC-7901 cells.
AB  - The objective of this paper was to investigate the antitumour mechanism of action
      of matrine by studying its inhibitory effect on gastric cancer SGC-7901 cells.
      SGC-7901 cells were chosen, and cell-killing capacity of matrine on gastric
      cancer SGC-7901 cells was determined using MTT assay and single PI staining
      assay. The results showed that matrine had an inhibitory effect on gastric cancer
      SGC-7901 cells, which was somewhat dose-dependent. The study concluded that
      matrine has a significant in-vitro inhibitory effect on SGC-7901 tumour cells,
      influences cell cycle of SGC-7901 cells, and induces their apoptosis. 

PMID- 24311864
TI  - A study on the inhibitory effect of polysaccharides from Radix ranunculus ternati
      on human breast cancer MCF-7 cell lines.
AB  - The objective of this paper was to study the in vitro anti-breast cancer activity
      of polysaccharides from Radix ranunculus ternati. Different concentrations of
      polysaccharide extracts were selected, and MTT assay and flow cytometry (FCM)
      were used to investigate their growth-inhibitory and apoptosis-inducing effects
      on human breast cancer MCF-7 cell lines. Radix ranunculus ternati polysaccharides
      had varying degrees of effects on the growth of human breast cancer MCF-7 cell
      lines, and the differences were significant compared with the blank control
      group. FCM showed that the polysaccharides can induce apoptosis. In addition, it
      can also enhance NK cell activity. Radix ranunculus ternati polysaccharides have
      a relatively good in-vitro anti-breast cancer activity. 

PMID- 24311865
TI  - A study on the inhibitory effect of Solanum lyratum Thunb extract on Lewis lung
      carcinoma lines.
AB  - The objective of this paper was to observe the effects of Solanum lyratum Thunb
      extract on tumour inhibition, immune function and survival time of tumour-bearing
      mice. Lung carcinoma-bearing mouse model was established, the tumour-bearing mice
      were divided into model group, CTX group, Solanum lyratum Thunb extract high-dose
      group and low-dose group. By the examination of tumour inhibition rate of Solanum
      lyratum Thunb extract in Lewis lung carcinoma-bearing mice and determination of
      the number of NK cells and T cell subsets, the survival rate of tumour-bearing
      mice was observed. Solanum lyratum Thunb extract had some anti-tumour effect in
      Lewis tumour-bearing mice. The tumour inhibition rate of high-dose group reached
      46.28%, and the tumour inhibition rate of low-dose group was 31.42%. Solanum
      lyratum Thunb extract can improve the NK cell activity of Lewis tumour-bearing
      mice, increase the number of CD4 cells in the tumour-bearing mice, and
      significantly increase the survival rate of tumour-bearing mice. The study
      concluded that Solanum lyratum Thunb extract has some anti-tumour effect and can
      improve immune function and survival rate of tumour-bearing mice. 

PMID- 24311866
TI  - Treating cardiovascular atherosclerotic plaques with Tongmaijiangzhi (TMJZ)
      capsule.
AB  - Atherosclerotic plaques can cause serious syndromes and mortality. Cholesterol
      accumulation in the plaques can disrupt the arterial flow, with lumen narrowing
      and stenosis, which contributes to heart attack and sudden cardiac death. The
      pharmacological treatment to atherosclerotic plaques can be anti-hypertensives,
      anti-cholesterol, and cleaning of the existed plaques. This work examined the
      effects of pharmacological Tongmaijiangzhi (TMJZ) capsule on atherosclerotic
      plaques. The radiological findings of the atherosclerotic plaques of 107 patients
      receiving TMJZ treatment were analyzed. We found that the TMJZ administration
      decreases plaque volume and alters the composition in a relatively short period,
      showing highly promising effects. TMJZ treatment is able to remove the existed
      atherosclerotic plaques with no side effects observed. 

PMID- 24311867
TI  - Screening of various botanical extracts for antioxidant activity using DPPH free
      radical method.
AB  - Aiming at the exploration of herbal use by society, crude extracts of the seeds
      of some commonly used medicinal plants (Vitis vinifera, Tamarindus indica and
      Glycin max) were screened for their free radical scavenging properties using
      ascorbic acid as standard antioxidant. Free radical scavenging activity was
      evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. The overall
      antioxidant activity of grape seeds (Vitis vinifera) was the strongest, followed
      in descending order by soybean (Glycin max) and tamarind (Tamarindus indica). The
      seeds extract of Vitis vinifera, Glycin max and Tamarindus indica showed 85.61%,
      83.45% and 79.26%, DPPH scavenging activity respectively. 

PMID- 24311868
TI  - Study on optimisation of extraction process of tanshinone IIA and its mechanism
      of induction of gastric cancer SGC7901 cell apoptosis.
AB  - The objective of this paper was to investigate the extraction process of
      tanshinone IIA and its mechanism of induction of gastric cancer SGC7901 cell
      apoptosis. Extraction process of tanshinone IIA was optimised by orthogonal
      experimental method, and its effect on gastric cancer SGC7901 cell apoptosis was
      observed using MTT assay and electron microscopy. The optimum extraction process
      of tanshinone IIA was as follows: addition of a 10-fold amount of 80% ethanol,
      one-time extraction, and extraction time of 45 minutes. The study concluded that
      tanshinone IIA can induce apoptosis of gastric cancer SGC7901 cells. 

PMID- 24311869
TI  - A study on the antitumour effect of total flavonoids from Pteris multifida Poir
      in H22 tumour-bearing mice.
AB  - The objective of this paper was to investigate the inhibitory effect of total
      flavonoids from Pteris multifida Poir on growth of transplanted H22 tumour in
      mice. H22 tumour-bearing mice model was established; the experimental animals
      were divide/d into the model group, Pteris multifida Poir total flavonoids high-,
      low-dose groups, and CTX group. Pteris multifida Poir groups were administered
      continuously for 10d, and CTX group was administered every other day. Tumour
      inhibition rate, thymus index and spleen index were calculated. Serum levels of
      TNF-alpha and IL-2 were determined, as well as total antioxidant capacity (T-AOC)
      and malondialdehyde (MDA) levels in serum. Compared with the model group, the
      total flavonoids of Pteris multifida Poir can significantly inhibit tumour
      growth, with tumour inhibition rates of high-and low-dose groups 49.36% and
      33.97%, respectively. They can also evidently increase the spleen and thymus
      indices of tumour-bearing mice, elevate serum TNF-alpha and IL-2 levels increase
      serum T-AOC level and reduce serum MDA level in tumour-bearing mice. The study
      concluded that total flavonoids from Pteris multifida Poir has an obvious
      inhibitory effect on transplanted H22 tumours; its mechanism of action may be
      associated with the improvement of immune function and enhancement of antioxidant
      capacity in mice. 

PMID- 24311870
TI  - A study on screening of osteosarcoma U2OS cell inhibiting active components from
      nidus vespae.
AB  - This paper mainly examined the anti-osteosarcoma activity of total flavonoids
      extract from traditional Chinese medicine, nidus vespae. Orthogonal design was
      used to design the extraction process of total flavonoids. L(3(4)) orthogonal
      test was performed and the extracts obtained by three optimal extraction
      processes were used for anti-tumour activity screening in order to determine the
      optimal anti-tumour effective component of nidus vespae. MTT assay was used to
      investigate the effect of nidus vespae extract on proliferation activity of
      osteosarcoma cells. Meanwhile, U2OS cell inhibitory capacities of extracts in
      three groups with higher total flavonoid contents were investigated and compared,
      and inhibition rates were calculated. The results showed that the optimal
      extraction process was ethanol concentration of 95%, 12-fold amount of ethanol
      relative to the weight of medicinal material, extraction times of 3 times, and
      extraction time of 2 hours. 9 extraction processes all showed proportional trend
      of cancer cell inhibition rate to extract concentration. 

PMID- 24311871
TI  - Evaluation of antitrypanosomal and anti inflammatory activities of selected
      Nigerian medicinal plants in mice.
AB  - The extracts of nine selected Nigerian medicinal plants were investigated on
      Trypanosoma brucei brucei infected mice. The anti-inflammatory properties of
      hexane fraction of the most promising U. chamae extract was assessed by acute
      oedema of the mice paw model while the modulatory effect of the extract on
      Delayed-Type Hypersensitivity (DTH) response on in vivo leucocytes mobilization
      was evaluated. 'Dose-probing acute toxicity tests' established an oral and
      intraperitoneal LD50 for T. ivorensis stem bark as >1600 < 5000 mg/kg and 100
      mg/kg respectively, while the oral LD50 of Uvaria. chamae was >5000 mg/kg.
      Extracts of Khaya senegalensis, Harungana madagascariensis, Terminalia ivorensis,
      Curcuma longa, Ocimum gratissimum and Alcornea cordifolia showed weak anti
      trypanosomal effect and did not exhibit significant clearance in parasitemia at
      the test dose administered compared with the positive control (Diminal(r)).
      However, the leaf extract of U. chamae and its hexane fraction demonstrated a
      significant response (P < 0.01). The fraction at 1000 mg/kg inhibited oedema by
      107%. Uvaria. chamae demonstrated both antitrypanosomal and anti-inflammatory
      properties by increasing the survival time of infected mice due to reduction in
      parasitemia caused by T. brucei brucei. 

PMID- 24311872
TI  - Effect of rosmarinic acid on sertoli cells apoptosis and serum antioxidant levels
      in rats after exposure to electromagnetic fields.
AB  - Rosmarinic acid belongs to the group of polyphenols; it has antioxidant, anti
      inflammatory and antimicrobial activities and help to prevent cell damage caused
      by free radicals. The objective was to study the effect of Rosmarinic acid on
      sertolli cells apoptosis and serum antioxidant levels in rats after they were
      exposed to electromagnetic fields. Male Wistar rats (n=40) were allocated into
      three groups: control group (n=10) that received 5 cc normal saline (0.9% NaCl)
      daily by gavage method, Rosmarinic acid group that received 5mg/rat (gavage)
      (n=10), electromagnetic fields (EMF) group that had exposure with 50 hz (n=20)
      which was subdivided to two groups of 10; EMF group and treatment group.
      Treatment group received 5mg/rat (gavage) Rosmarinic acid daily for 6 weeks,
      respectively. However, the control group just received an equal volume of
      distilled water daily (gavage). On the 42nd day of research, 5 cc blood was
      collected to measure testosterone hormones, total antioxidant capacity (TAC),
      levels from whole group's analysis. Level of malondialdehyde (MDA) levels and
      sertoli cells apoptosis significantly decreased in the group that received
      5mg/rat of Rosmarinic acid (P<0.05) in comparison with experimental groups. Level
      of testosterone, total antioxidant capacity (TAC), significantly increased in
      groups that received Rosmarinic acid (P<0.05). Since in our study 5mg/rat of
      Rosmarinic acid showed significantly preventive effect on cell damages especial
      sertoli cells apoptosis that caused with EMF, it seems that using Rosmarinic acid
      as food additive can be effective for supporting people living under EMF
      environmental pollution.

PMID- 24311873
TI  - A study on the antioxidant effect of Coriolus versicolor polysaccharide in rat
      brain tissues.
AB  - The objective of the study was to investigate the antioxidant effect of Chinese
      medicine Coriolus versicolor polysaccharide on brain tissue and its mechanism in
      rats. SOD, MDA and GSH-Px levels in rat brain tissues were determined with SD
      rats as the animal model. The results showed that Coriolus versicolor
      polysaccharide can reduce the lipid peroxidation level in brain tissues during
      exhaustive exercise in rats, and can accelerate the removal of free radicals. The
      study concluded that its antioxidant effect is relatively apparent. 

PMID- 24311874
TI  - A study on the extraction and purification process of lily polysaccharide and its
      anti-tumor effect.
AB  - The objective of this paper was to extract and purify lily polysaccharide and to
      study its anti-H22 hepatoma effect in mice. Orthogonal experimental method was
      used to analyze the factors influencing the extraction and purification of lily
      polysaccharide, and the anti-tumor effect of lily polysaccharide was studied by
      acting it on H22-bearing mice. The results showed that the size of influence of
      various factors on the extraction results of lily polysaccharide were extraction
      time, extraction times and extraction temperature in decreasing order. Lily
      polysaccharide can enhance the immune function of H22 tumor-bearing mice, and
      inhibit the growth of H22 tumor. The study concluded that the optimal conditions
      for the extraction and purification of lily polysaccharide should be extraction
      times of 3 times, an extraction time of 4 h each, and an extraction temperature
      of 60 degrees C; lily polysaccharide has an anti-tumor effect. 

PMID- 24311875
TI  - Effect of ethanol extract of Selaginella doederleinii Hieron on the proliferation
      of nasopharyngeal carcinoma CNE-1 and C666-1 cells.
AB  - This paper mainly studied the effect of ethanol extract of Selaginella
      doederleinii Hieron on the proliferation of two kinds of nasopharyngeal carcinoma
      cell lines, CNE-1 and C666-1, and their mechanisms of action. Extract was
      obtained by heat reflux extraction with ethanol, and the effect of extract on the
      extracellular matrix adhesion of the cells, on their proliferation process, as
      well as on their colony-forming ability were tested using MTT assay. The results
      showed that the yield of dry extract was 36.4%. 2.5 g/ml extract in the high
      concentration group exhibited inhibitory activity that was directly proportional
      to the concentration on CNE-1 cells, while not exhibiting obvious proportional
      trend in respect with C666-1 cells. However, the inhibition rates against two
      types of cells can both reach between 30% ~ 50%. Under the effect of ethanol
      extract of Selaginella doederleinii Hieron, proliferative capacities of C666-1
      and CNE-1 cells were affected to some extent.

PMID- 24311876
TI  - A study on four antioxidation effects of lycium barbarum polysaccharides in
      vitro.
AB  - The objective of the study was to investigate the in vitro antioxidation activity
      of lycium barbarum polysaccharides (LBP). Ultraviolet spectrophotometry was
      adopted to determine the capability of LBP to clear superoxide anions, hydroxyl
      radicals, DPPH free radicals and ABTS free radicals. The result showed that the
      law for LBP to clear superoxide anions, hydroxyl radicals and DPPH free radicals
      was that the clearance rate increased gradually with the increase of the
      concentration, and when the concentration reached a certain value, the clearance
      rate leveled off, while the IC50 for clearing ABTS free radicals was 47.158 +/-
      6.231 ug/ml. The study concluded that LBP is a good in vitro antioxidant.

PMID- 24311877
TI  - Antispasmodic effects of yarrow (Achillea millefolium L.) extract in the isolated
      ileum of rat.
AB  - Achillea millefolium L. is cultivated in Iran and widely used in traditional
      medicine for gastrointestinal disorders. The aim of this study was to determine
      the effect of hydroalcoholic extract of A. millefolium on the contraction and
      relaxation of isolated ileum in rat. In this experimental study, aerial parts of
      A. millefolium were extracted by maceration in ethanol 70% for 72 h. Terminal
      portion of ileum in 100 male Wistar rats was dissected and its contractions were
      recorded isotonically in an organ bath containing Tyrode solution (37  degrees C,
      pH 7.4) under one gram tension. Acetylcholine (1mM) and KCl (60mM) were used to
      create isotonic contractions. Propranolol and Nomega-Nitro-L-arginine methylester
      hydrochloride (L-NAME) were used to investigate the mechanisms of action prior to
      giving the extract to the relevant groups. Data were compared by ANOVA and
      Turkey's post hoc test.. The results showed that the ileum contraction was
      induced by KCl and acetylcholine induced contraction was significantly reduced by
      A. millefolium extract. The cumulative concentrations of A. millefolium relaxed
      the KCl and acetylcholine induced contractions (n=14, p<0.001). The inhibitory
      effect of extract on contraction induced by KCl and acetylcholine was not
      significantly affected neither by propranolol (1uM) nor by L-NAME (100 uM). There
      was no significant difference in the rate of relaxation by propranolol and L-NAME
      between the two groups. In conclusion, A. millefolium can inhibit contraction of
      smooth muscle of ileum in rat, and it can be used for eliminating intestinal
      spasms. These results suggest that the relaxatory effect of A. millefolium on
      ileum contractions can be due to the blockade of voltage dependent calcium
      channels. In addition, the beta-adrenoceptors, cholinergic receptors and nitric
      oxide production are not powerful actors in inhibitory effect of A. millefolium.
      So, the nitric oxide and adrenergic systems may also be involved in the
      antispasmodic effect of A. millefolium.

PMID- 24311878
TI  - Evaluation of the toxicological profile of the leaves and young twigs of
      Caesalpinia bonduc (Linn) roxb.
AB  - Acute and sub-acute toxicological effects of ethanolic extract of the leaves and
      young twigs of Caesalpinia bonduc were carried out on albino rats. Single extract
      doses from 2000 to 5000 mg/kg body weight were administered orally and monitored
      for 14 days in acute study, while extract doses from 200 to 1600 mg/kg body
      weight were orally administered daily for 28 days in sub-acute study and recovery
      was assessed 14 days after dosing. Biochemical, haematological and
      histopathological examinations were carried out. There was no mortality in the
      experimental animals in all acute treatment doses. However, there were
      significant alterations in the biomarkers and induced cellular damage to the
      liver in all acute treatment doses. In the sub-acute toxicity treatment, the
      assessed biomarkers were unaffected at extract dose of 200 mg/kg body weight
      compared to control, while significant changes were observed in rats administered
      with extract doses of 400 mg/kg body weight and above. No significant difference
      was observed between the tested groups and the recovery groups in the sub-acute
      toxicity study. In conclusion, the ethanolic extract of C. bonduc could be toxic
      to selected organs of the rat body in acute and sub-acute treatments. 

PMID- 24311879
TI  - The antimicrobial assessment of some Nigerian herbal soap.
AB  - Twenty samples of herbal soaps were evaluated for their antimicrobial activity
      against bacteria and yeast of significance in skin infections with the aim to
      provide some justification for the continued use of the soaps in the management
      of superficial skin infections. All the soaps were found to possess antimicrobial
      activity in a concentration and organism dependent manner. The soaps were more
      active against the gram positive organisms than the Gram negative organisms while
      none of the soaps had activity against the tested yeasts. Only 35% of the soaps
      were appropriately packaged with adequate directions for use and storage. The
      study showed that the tested soaps possessed antimicrobial properties and they
      can contribute to the treatment and management of skin infections caused by
      bacteria if well prepared with the appropriate plant materials to target specific
      causative organisms and packaged with appropriate directions for use and storage.

PMID- 24311880
TI  - Erythrocyte membrane fatty acids in multiple sclerosis patients and hot-nature
      dietary intervention with co-supplemented hemp-seed and evening-primrose oils.
AB  - The risk of developing multiple sclerosis (MS) is associated with increased
      dietary intake of saturated fatty acids. For many years it has been suspected
      that this disease might be associated with an imbalance between unsaturated and
      saturated fatty acids. We determined erythrocyte membrane fatty acids levels in
      Hot nature dietary intervention with co-supplemented hemp seed and evening
      primrose oils in multiple sclerosis patients. To determine the erythrocyte
      membrane fatty acids levels and correlate it with expanded disability status
      scale (EDSS) at baseline after 6 months intervention in MS patients by gas
      chromatography, in this double blind, randomized trial, 100 RRMS patients with
      EDSS<6 were allocated into three groups: "Group A" that received co-supplemented
      hemp seed and evening primrose oils with advised Hot nature diet. "Group B"
      received olive oil and "Group C" received the co-supplemented oils. The results
      showed that the mean follow-up was 180 +/- 2.9SD days (N=65, 23 M and 42 F aged
      34.25 +/- 8.07 years with disease duration of 6.80 +/- 4.33 years). There was no
      significant difference in the study parameters at baseline. After 6 months, EDSS,
      Immunological parameters and the erythrocyte cell membrane with regard to
      specific fatty acids showed improvement in the group A and C, whereas there was
      worsening condition for the group B after the intervention. We concluded that Hot
      nature dietary intervention with co-supplemented hemp seed and evening primrose
      oils caused an increase PUFAs in MS patients and improvement in the erythrocyte
      membrane fatty acids composition. This could be an indication of restored plasma
      stores, and a reflection of disease severity reduction.

PMID- 24311881
TI  - Antimicrobial and antiplasmodial activities of a quaternary compound from
      Ritchiea capparoides var. longipedicellata.
AB  - The leaves of Ritchiea capparoides var. longipedicellata (Capparidaceae) is used
      in ethnomedicine in South-Western Nigeria to treat infectious and parasitic
      diseases. This study was aimed at identifying the compound(s) that are
      responsible for the antimicrobial and antiplasmodial activities of the leaves and
      also to contribute to the chemistry of the plant species. A 70 % aqueous
      ethanolic extract of the leaves of R. longipedicellata was subjected to repeated
      liquid chromatographic methods on silica gel, Lobar RP-18 column and Sephadex LH
      20 to isolate a Draggendorf positive compound. The compound was identified by
      (1)H and (13)C NMR, ultra-violet spectroscopy and polarimetry. The antimicrobial
      activity of the compound was evaluated using the microbroth dilution method while
      the antiplasmodial activity was carried out according to Trager and Jenson
      (1976). The minimum inhibitory concentration (MIC) was expressed in mg/ml. The
      isolated compound, leavoisomer of stachydrine, inhibited the growth of
      Escherichia coli NCTC 8196 and Staphylococcus aureus NCTC 6571 at the MIC of 5
      mg/ml. In the anti-malaria assay, the compound had inhibitory activity with the
      concentration required to cause 100% lethality being 0.667 mg/ml. CONCLUSION: The
      antibacterial and antiparasitic effects of quaternary ammonium compounds are well
      documented. However, this study is the first report of the presence and
      biological activities of this compound in this plant species which may justify
      the ethnomedicinal uses of the leaves.

PMID- 24311882
TI  - A review of the pharmacological mechanism of traditional Chinese medicine in the
      intervention of coronary heart disease and stroke.
AB  - In recent years, several researches have showed that Buyang Huanwu Decoction
      (BHD) possesses multiple target points in the intervention of diseases, and has
      same treatment effects on cerebrovascular diseases and cardiovascular diseases.
      But, there was no full report about the mechanistic and material basis in Brain
      Heart concurrent treatment. The objective of the present study was to examine the
      pharmacological mechanism of traditional Chinese medicine in the intervention of
      coronary heart disease and stroke. We combined the HIT, PubChem, David Database
      resource and the networked pharmacology method to ultimately find out BHD's
      thirty-five potential brain-heart concurrent treatment target points, and
      preliminarily reveal BHD's material basis for treatment of cerebrovascular
      diseases and cardiovascular diseases. Finally, the study provided new information
      with the guidance meanings. 

PMID- 24311883
TI  - A study on the effect of ethanol extract of Radix rhapontici on erythrocyte
      immune function in rats.
AB  - This paper mainly studied the effect of ethanol extract of Radix rhapontici on
      erythrocyte immune function in SD rats with acute blood stasis. The methods used
      the effect on erythrocyte immune function. After intragastric administration of
      suspension of ethanol extract of Radix rhapontici to SD rats for 3 weeks, on the
      21st day from intragastric administration, SD rats were made into blood stasis
      model and bloods were collected to determine the C3b, C3bRR, RFIR, and RFER in
      erythrocyte immune function. Meanwhile, serum total antioxidant activity (TAA),
      superoxide dismutase (SOD) activity, and serum malondialdehyde (MDA) level of
      rats were determined, and experimental results were analysed with analysis of
      variance and Q test. The results showed that the ethanol extract of Radix
      rhapontici had a very good effect on enhancement of erythrocyte immune function
      in SD rats. 

PMID- 24311884
TI  - Anticancer effects of Ligusticum chuanxiong Hort alcohol extracts on HS766T cell.
AB  - This research was mainly to study the optimisation of extraction process of
      Ligusticum chuanxiong Hort alcohol extracts. Stable passage pancreatic cancer HS
      766 T cell lines were created by cell culture, and the cell proliferation data
      were measured by MTT assay. The determination of HS766T cell cycle and apoptosis
      case was done by PI staining and flow cytometry analysis. The results displayed
      that Ligusticum chuanxiong Hort can inhibit the proliferation of pancreatic
      cancer HS 766 T cells. The cell cycle was blocked in G0/G1 phase, and the cell
      membrane was damaged on observation with microscope. At the same time, the
      generation of apoptosis was promoted by reduced intracellular Ca(2+)
      concentration. All in all, the HS 766 T cells could be effectively suppressed by
      Ligusticum chuanxiong Hort alcohol extracts. 

PMID- 24311885
TI  - An experimental study on the anti-Ehrlich ascites carcinoma effect of purified
      toad venom extract.
AB  - The objective of this paper was to study the anti-Ehrlich ascites carcinoma
      effect of purified toad venom extract and its mechanism. Mouse model of Ehrlich
      ascites carcinoma was established with cisplatin as the control to observe the
      inhibitory effect of purified toad venom extract on malignant peritoneal effusion
      in mice. The results showed that compared with the control group, ascites volume,
      number of tumour cells and tumour cell viability decreased and ascites inhibition
      rate reached over 50% in each treatment group, and with the increase of the dose,
      incidence of ascites showed a downward trend. The number of tumour cells in
      ascites and tumour cell viability in the purified toad venom high-dose group were
      lower than those of the cisplatin group. Compared with the model group, survival
      time was prolonged in varying degrees in the purified toad venom groups and
      cisplatin group. The study concluded that purified extract of toad venom has an
      anti-Ehrlich ascites carcinoma effect. 

PMID- 24311886
TI  - A study on the anticancer activity of ethanol extract of Aristolochia mollissima
      Hance on osteosarcoma HOS cells.
AB  - This paper mainly studied the extraction process of traditional Chinese medicine
      Aristolochia mollissima Hance (Aristolochiaceae) and the inhibitory effect of its
      extracts on osteosarcoma HOS cells. The extraction process included the
      ultrasonic extraction method, heat reflux method and decoction method to obtain
      three different extracts. MTT assay was used to test the effect of the extracts
      on proliferation of HOS cells, to compare the degree of inhibitory activity of
      three extracts, and to calculate cell survival rates. The results showed that
      among the three extracts obtained by the ultrasonic extraction method, heat
      reflux method and decoction method, the one obtained by ultrasonic extraction has
      the largest yield, but the extract obtained by heat reflux method has the
      strongest anticancer activity. Nevertheless, the three extracts all have a good
      inhibitory activity on the proliferation of osteosarcoma HOS cells. 

PMID- 24311887
TI  - The effect of altitude on breaking seed dormancy and stimulation of seed
      germination of Persian hogweed (Heracleum persicum).
AB  - Persian hogweed is a perennial herb and aromatic plant which has pharmaceutical
      and fodder values, and the main propagation method of this species is seed. The
      goal of this study was to investigate the effect of altitude on breaking dormancy
      and stimulate seed germination of this species. The study was designed and
      carried out using the test of seed analysis. For our purpose, seeds were
      collected from three different altitudes (1700, 2200, 2700 masl) in Kojoor area.
      After initial purification, germination percent (GP) and speed (GS) of each
      elevation were determined by cold stratification compared to control. According
      to results, control seeds did not germinate, showing that the seeds of this
      species need to be treated. Statistical analysis of results showed that there are
      significant differences between GP and GS of each elevation, as seeds of higher
      elevation had slower and less germination in longer periods. So, changes in
      elevation are an effective factor on seed germination characteristics of this
      species and this factor has to be considered in seed preparation and restoration
      with this species. 

PMID- 24311888
TI  - Antimicrobial activity of extracts from in vivo and in vitro propagated Lamium
      album L. plants.
AB  - The antimicrobial activity of 18 different extracts from in vivo and in vitro
      grown L. album L. plants was evaluated against clinical bacteria and yeasts using
      the well diffusion method. All the used extracts demonstrated antibacterial
      activity, whereas only the water extracts from leaves (in vivo) possessed
      antifungal activity against Candida albicans NBIMCC 72 and Candida glabrata
      NBIMCC 8673 (14 and 20 mm diameter of inhibition zones and MIC 10 mg/ml,
      respectively). The methanol and ethanol extracts obtained from the in vitro
      propagated plants had a broader spectrum of antibacterial activity than those
      from in vivo plants, while the opposite tendency was observed for the chloroform
      extracts. All tested flower extracts possessed antimicrobial activity. The
      chloroform extract from in vivo flowers demonstrated the highest activity against
      E. faecalis NBIMCC 3915, S. aureus NBIMCC 3703, P. hauseri NBIMCC 1339 and P.
      aeruginosa NBIMCC 3700 (22 mm, 13 mm, 11 mm, 23 mm zone diameter of inhibition
      and MIC 0.313 mg/ml, respectively). The water extracts from leaves (both in vivo
      and in vitro) possessed higher antibacterial activity than extract from flowers.
      The obtained results showed that both in vivo and in vitro propagated L. album L.
      could be used as a source of antibacterial substances. 

PMID- 24311889
TI  - A literature analysis on 14 cases of allergic shock caused by safflower
      injection.
AB  - The objective of this paper was to investigate the characteristics and general
      rules of domestic safflower injection causing allergic shock, to retrieve the
      medical journals published domestically, and to make statistical analysis on the
      cases of allergic shock caused by safflower injection. Results showed that the
      incidence of allergic shock caused by safflower injection in patients above 40
      years old was high: females were more than males. It occurred within 30 min after
      medication, and no patient died after emergency treatment. The study concluded
      that allergic shock caused by safflower injection is related to many factors, and
      clinical care personnel should pay more attention to it.

PMID- 24311890
TI  - Sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta
      cayennensis in mice.
AB  - The leaves are used ethnomedicinally in Nigeria and other parts of the world for
      insomnia and anxiety among other uses. The investigations sought scientific
      evidence for the ethnomedicinal use of the leaves for the management of insomnia
      and anxiety as well as the neural mechanisms for the activities. The sedative and
      anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis
      were examined in this study. The methanolic extract (5-50 mg/kg, i.p.) as well as
      the ethylacetate (10-50 mg/kg, i.p.), butanol and aqueous fractions (5-50 mg/kg,
      i.p.) of the extract were examined. Sedation was assessed as reduced novelty
      induced rearing (NIR), reduced spontaneous locomotor activity (SLA) and increased
      pentobarbitone-induced sleeping time (PIST) in mice. The anti-anxiety effect
      (methanol 2.5-5.0; butanol 5.0; aqueous 20.0; ethylacetate 25.0 mg/kg, i.p.) was
      assessed using an elevated plus maze. LD50 was calculated for the extract and the
      fractions after the intraperitoneal route of administration using the Locke
      method. The methanolic extract, the butanol and the aqueous fractions inhibited
      rearing and spontaneous locomotion but prolonged pentobarbitone induced sleep.
      The ethylacetate fraction however increased both rearing and locomotion and
      decreased pentobarbitone sleeping time. The butanol and aqueous fractions, but
      not the methanol extract showed indices of open arm avoidance consistent with
      anti-anxiety effect. Naltrexone (2.5 mg/kg, i.p.) reversed the inhibition of
      rearing, locomotion and prolongation of pentobarbitone sleep due to the aqueous
      fraction of the extract. Flumazenil (2mg/kg, i.p.) abolished the effects of both
      methanolic extract and the butanol fraction on rearing, locomotion,
      pentobarbitone sleep and anxiety model. The methanolic extract, the butanol and
      aqueous fractions possess sedative activity while the ethylacetate fraction
      possesses stimulant property. The anxiolytic effect was found in both the aqueous
      fraction and the butanol fraction but not in the main methanol extract and also
      not in the ethylacetate fraction. Flumazenil, blocked the effect of the leaves of
      Stachytarpheta cayennensis on rearing, locomotion and elevated plus maze
      suggesting that GABA receptors are involved in the observed sedative and
      anxiolytic activities. This study also found opioid receptors involved in the
      sedative activity of the leaves of Stachytarpheta cayennensis. The rationale for
      the ethnomedicinal use of the leaves for the management of insomnia and anxiety
      were confirmed scientifically in this study. 

PMID- 24311893
TI  - Structural Effects of Network Sampling Coverage I: Nodes Missing at Random1.
AB  - Network measures assume a census of a well-bounded population. This level of
      coverage is rarely achieved in practice, however, and we have only limited
      information on the robustness of network measures to incomplete coverage. This
      paper examines the effect of node-level missingness on 4 classes of network
      measures: centrality, centralization, topology and homophily across a diverse
      sample of 12 empirical networks. We use a Monte Carlo simulation process to
      generate data with known levels of missingness and compare the resulting network
      scores to their known starting values. As with past studies (Borgatti et al 2006;
      Kossinets 2006), we find that measurement bias generally increases with more
      missing data. The exact rate and nature of this increase, however, varies
      systematically across network measures. For example, betweenness and Bonacich
      centralization are quite sensitive to missing data while closeness and in-degree
      are robust. Similarly, while the tau statistic and distance are difficult to
      capture with missing data, transitivity shows little bias even with very high
      levels of missingness. The results are also clearly dependent on the features of
      the network. Larger, more centralized networks are generally more robust to
      missing data, but this is especially true for centrality and centralization
      measures. More cohesive networks are robust to missing data when measuring
      topological features but not when measuring centralization. Overall, the results
      suggest that missing data may have quite large or quite small effects on network
      measurement, depending on the type of network and the question being posed.

PMID- 24311892
TI  - Is transforming growth factor-beta signaling activated in human hypertrophied
      prostate treated by 5-alpha reductase inhibitor?
AB  - BACKGROUND AND AIM: It is well known that androgen deprivation relates to penile
      fibrosis, so we hypothesize that long-term treatment with 5-alphareductase
      inhibitors (5ARIs) may increase the risk of fibrosis of prostate. PATIENTS AND
      METHODS: Thirty-two BPH patients who underwent transurethral resection of the
      prostate were enrolled. The patients were divided into two groups: group one, 16
      patients underwent TURP who had been treated with tamsulosin for 2 years; group
      two, 16 patients underwent TURP who had been treated with combination of
      tamsulosin and dutasteride for at least 1 year. We evaluated the expressions of
      nNOS, iNOS, eNOS, TGF-beta1, TGF-beta2, phosphorylated-Smad2/3 (p-Smad2/3), E
      cadherin, N-cadherin, and alpha-smooth muscle actin in the resected prostate
      tissues by western blotting, and the TGF-beta concentration was determined by
      ELISA kit. RESULTS: The expressions of 3 isoforms of NOS were significantly
      increased in group 2 except of eNOS in lateral prostate, and the expressions of
      TGF-beta1, TGF-beta2, and p-Smad2/3 increased about 2-fold compared with group 1.
      In group 2, the E-cadherin expression decreased while N-cadherin expression
      increased significantly. CONCLUSIONS: The overexpression of nNOS may contribute
      to prostate smooth muscle relaxation; however, long-time treatment with 5 ARI
      increases the risk of fibrosis of prostate.

PMID- 24311894
TI  - Common African cooking processes do not affect the aflatoxin binding efficacy of
      refined calcium montmorillonite clay.
AB  - Aflatoxins are common contaminants of staple crops, such as corn and groundnuts,
      and a significant cause of concern for food safety and public health in
      developing countries. Aflatoxin B1 (AFB1) has been implicated in the etiology of
      acute and chronic disease in humans and animals, including growth stunting, liver
      cancer and death. Cost effective and culturally acceptable intervention
      strategies for the reduction of dietary AFB1 exposure are of critical need in
      populations at high risk for aflatoxicosis. Fermented gruels consisting of
      cornmeal are a common source for such exposure and are consumed by both children
      and adults in many countries with a history of frequent, high-level aflatoxin
      exposure. One proposed method to reduce aflatoxins in the diet is to include a
      selective enterosorbent, Uniform Particle Size NovaSil (UPSN), as a food additive
      in contaminated foods. For UPSN to be effective in this capacity, it must be
      stable in complex, acidic mixtures that are often exposed to heat during the
      process of fermented gruel preparation. Therefore, the objective of the present
      study was to test the ability of UPSN to sorb aflatoxin while common cooking
      conditions were applied. The influence of fermentation, heat treatment, acidity,
      and processing time were investigated with and without UPSN. Analyses were
      performed using the field-practical Vicam assay with HPLC verification of trends.
      Our findings demonstrated that UPSN significantly reduced aflatoxin levels (47
      100%) in cornmeal, regardless of processing conditions. Upon comparison of each
      element tested, time appeared to be the primary factor influencing UPSN efficacy.
      The greatest decreases in AFB1 were reported in samples allowed to incubate (with
      or without fermentation) for 72 hrs. This data suggests that addition of UPSN to
      staple corn ingredients likely to contain aflatoxins would be a sustainable
      approach to reduce exposure.

PMID- 24311897
TI  - Robot assisted laparoscopic retroperitoneal lymph node dissection in testicular
      tumor.
AB  - The treatment options in clinical stage I nonseminomatous germ cell tumor (NSGCT)
      of testis are either surveillance, chemotherapy or retroperitoneal lymph node
      dissection (RPLND). While open RPLND still serves as the gold standard,
      laparoscopic and robot assisted laparoscopic approaches are gaining popularity.
      In this report, we share our experience and technique of robot assisted
      laparoscopic RPLND in a patient with clinical stage Ib NSGCT of testis. 

PMID- 24311896
TI  - The role of EGFR/PI3K/Akt/cyclinD1 signaling pathway in acquired middle ear
      cholesteatoma.
AB  - Cholesteatoma is a benign keratinizing and hyper proliferative squamous
      epithelial lesion of the temporal bone. Epidermal growth factor (EGF) is one of
      the most important cytokines which has been shown to play a critical role in
      cholesteatoma. In this investigation, we studied the effects of EGF on the
      proliferation of keratinocytes and EGF-mediated signaling pathways underlying the
      pathogenesis of cholesteatoma. We examined the expressions of phosphorylated EGF
      receptor (p-EGFR), phosphorylated Akt (p-Akt), cyclinD1, and proliferating cell
      nuclear antigen (PCNA) in 40 cholesteatoma samples and 20 samples of normal
      external auditory canal (EAC) epithelium by immunohistochemical method.
      Furthermore, in vitro studies were performed to investigate EGF-induced
      downstream signaling pathways in primary external auditory canal keratinocytes
      (EACKs). The expressions of p-EGFR, p-Akt, cyclinD1, and PCNA in cholesteatoma
      epithelium were significantly increased when compared with those of control
      subjects. We also demonstrated that EGF led to the activation of the
      EGFR/PI3K/Akt/cyclinD1 signaling pathway, which played a critical role in EGF
      induced cell proliferation and cell cycle progression of EACKs. Both EGFR
      inhibitor AG1478 and PI3K inhibitor wortmannin inhibited the EGF-induced
      EGFR/PI3K/Akt/cyclinD1 signaling pathway concomitantly with inhibition of cell
      proliferation and cell cycle progression of EACKs. Taken together, our data
      suggest that the EGFR/PI3K/Akt/cyclinD1 signaling pathway is active in
      cholesteatoma and may play a crucial role in cholesteatoma epithelial hyper
      proliferation. This study will facilitate the development of potential
      therapeutic targets for intratympanic drug therapy for cholesteatoma. 

PMID- 24311898
TI  - Robot assisted laparoscopic retroperitoneal lymph node dissection in testicular
      tumor.

PMID- 24311895
TI  - Biomarkers in diabetic retinopathy and the therapeutic implications.
AB  - The main problem both in type 1 (T1DM) and type 2 (T2DM) diabetes is the
      development of chronic vascular complications encompassing micro- as well as
      macrocirculation. Chronic complications lower the quality of life, lead to
      disability, and are the cause of premature death in DM patients. One of the
      chronic vascular complications is a diabetic retinopathy (DR) which leads to a
      complete loss of sight in DM patients. Recent trials show that the primary cause
      of diabetic retinopathy is retinal neovascularization caused by disequilibrium
      between pro- and antiangiogenic factors. Gaining knowledge of the mechanisms of
      action of factors influencing retinal neovascularization as well as the search
      for new, effective treatment methods, especially in advanced stages of DR, puts
      special importance on research concentrating on the implementation of biological
      drugs in DR therapy. At present, it is antivascular endothelial growth factor and
      antitumor necrosis factor that gain particular significance. 

PMID- 24311899
TI  - Analysis of short-term results of monsieur's tunica albuginea urethroplasty as a
      definitive procedure for pan-anterior urethral stricture.
AB  - CONTEXT: Long anterior urethral strictures are fairly common in developing world
      and the treatment is equally challenging. AIM: To assess the results and efficacy
      of Monsieur's Tunica Albuginea Urethroplasty (TAU) for anterior urethral
      stricture. SETTINGS AND DESIGN: We analyzed the results in 10 consecutive
      patients with pan-anterior urethral stricture, who underwent Monsieur's
      urethroplasty. MATERIALS AND METHODS: The procedure involves mobilization of
      strictured urethra and laying it open with a dorsal slit. Edges of the slit-open
      urethra are sutured to edges of the urethral groove to the tunica of corporal
      bodies with catheter in situ. Results were assessed postoperatively 3, 6, 9 and
      12 months. Patients were categorized as success and failure by comparative
      analysis of patient satisfaction along with urethroscopy, retrograde urethrogram,
      uroflowmetry. All patients were taken for post-operative urethroscopic analysis
      at 6 months to allow better understanding of both successful and failed cases.
      RESULTS: Mean follow-up of 15.2 (11-19) months showed an 80% success rate. Mean
      uroflow rate showed Qmax 24.5 cc/sec with 8 cases showing no residual or
      recurrent stricture. Two cases failed and required intervention. Urethroscopic
      visualization of the reconstruction site showed wide, patent and distensible
      neourethra appearing epithelized over roof formed by tunica albuginea of the
      corpora cavernosa in successful cases. CONCLUSION: Monsieur's TAU is effective
      technique in treatment of anterior urethral stricture especially cases with
      unavailable buccal mucosa, with results fairly acceptable at the end of one year.

PMID- 24311900
TI  - Vesicoureteric reflux in children.
AB  - AIM: This study aimed to identify the differences between primary and secondary
      vesicoureteric reflux (VUR) and the effect of associated bladder abnormalities on
      kidney function. PATIENTS AND METHODS: We retrospectively reviewed the medical
      records of children with VUR who were followed up at King Abdulaziz University
      Hospital from January 2005 to December 2010. The review included results of
      radiological investigations and kidney function tests. We used Chi-square test
      for statistical analysis and paired t-test to compare group means for initial and
      last creatinine levels. RESULTS: Ninety-nine children were included in this
      study. Twenty (20.2%) had primary VUR, 11 had high-grade VUR, while 9 had low
      grade reflux. All children with low-grade VUR had normal dimercaptosuccinic acid
      (DMSA). Renal scars were present in 72% of the children with high-grade VUR. The
      mean creatinine levels (initial and last) for both groups were normal. Seventy
      nine (79.8%) children had secondary VUR, which was due to posterior urethral
      valves (PUV) (46.8%), neurogenic bladder caused by meningomyelocele (25.3%), non
      neurogenic neurogenic bladder (NNB) (21.5%), or neurogenic bladder associated
      with prune belly syndrome (6.3%). Children with NNB, meningomyelocele and PUV had
      high creatinine at presentation with no considerable worsening of their kidney
      functions during the last visit. Renal scars were present in 49.4% of the
      children with secondary VUR. CONCLUSION: Children with primary VUR and normal
      bladder had good-functioning kidneys, while those with secondary VUR associated
      with abnormal bladder caused by NNB, spina bifida or PUV had abnormal kidney
      functions. DMSA scans were useful in predicting higher grades of VUR in children
      with primary reflux.

PMID- 24311901
TI  - Evaluation of the effect of sildenafil and/or doxazosin on Benign prostatic
      hyperplasia-related lower urinary tract symptoms and erectile dysfunction.
AB  - PURPOSE: To verify the association between lower urinary tract symptoms (LUTS)
      and erectile dysfunction (ED) and evaluate the influence of sildenafil and
      doxazosin either as single agents or combined on both symptoms. MATERIAL AND
      METHODS: A prospective randomized study including 150 patients presented with
      LUTS caused by BPH in association with clinically diagnosed ED, with age equal or
      more than 45 years from April 2010 to April 20011. They were categorized into
      three comparative groups each one containing 50 patients. These groups were
      comparable regarding pretreatment international prostate symptoms score (IPSS)
      and international index of erectile function (IIEF). The patients of the first
      group were given sildenafil 50 mg as monotherapy, those of the second group were
      given doxazosin 2 mg and those of the third group were given combination of both
      drugs for 4 months for each group. The main post-treatment parameters for
      assessment and comparison include assessment of patient's symptoms by repeated
      IPS Sand IIEF, uroflowmetry and assessment of PVR. The statistics was done by use
      of the Qui--square test. RESULTS: Pre-treatment parameters were assessed and
      compared between the three groups. After 4 months of treatment, the comparative
      parameters were applied to all groups and the differences were measured post
      treatment regarding IPSS, erectile function score, uroflowmetry, and post-void
      residual (PVR) urine. Sildenafil alone caused mild improvement in IPSS, more
      improvement in IIEF score, and little effect on flow rate and PVR urine.
      Doxazosin alone caused more improvement in IPSS, flow rate and PVR urine and less
      improvement in IIEF score. A combination of both sildenafil and doxazosin caused
      more improvement in all of the comparative parameters than when each drug was
      given alone. CONCLUSIONS: There is a strong relationship between LUTS and ED.
      Doxazosin or sidenafil as a single drug could be used in treating mild or mild to
      moderate symptoms but more severe symptoms may usually need a combination of both
      drugs.

PMID- 24311902
TI  - Management of symptomatic ureteral calculi during pregnancy: Experience of 23
      cases.
AB  - PURPOSE: To present our experience in the management of symptomatic ureteral
      calculi during pregnancy. MATERIALS AND METHODS: Twenty-three pregnant women,
      aged between 19 and 28 years presented to the obstetric and urology departments
      with renal colic (17 cases, 73.9%) and fever and renal pain (6 cases, 26.1%);
      suggesting ureteric stones. The diagnosis was established by ultrasonography
      (abdominal and transvaginal). Outpatient follow-up consisted of clinical
      assessment and abdominal ultrasonography. Follow-up by X-ray of the kidneys,
      ureter, and bladder (KUB), or intravenous urography (IVU) was done in the
      postpartum period. RESULTS: Double J (DJ) stent was inserted in six women (26%)
      with persistent fever followed by extracorporeal shock wave lithotripsy (ESWL)
      one month post-partum. Ureteroscopic procedure and pneumatic lithotripsy were
      performed for 17 women (distal ureteric stone in 10, middle ureter in 5, and
      upper ureteric stone in 2). Stone-free rate was 100%. No urologic, anesthetic, or
      obstetric complications were encountered. CONCLUSIONS: Ureteroscopy, pneumatic
      lithotripsy, and DJ insertion could be a definitive and safe option for the
      treatment of obstructive ureteric stones during pregnancy.

PMID- 24311903
TI  - Balloon dilatation for male urethral strictures "revisited".
AB  - AIMS: To analyze the results of balloon dilatation for short segment male
      urethral strictures. MATERIALS AND METHODS: Retrospective analysis was done of
      120 patients undergoing urethral balloon dilatation since January 2004 to January
      2012. The inclusion criteria for analysis was a short segment (less than 1.5 cm)
      stricture, exclusion criteria were pediatric, long (more than 1.5 cm), traumatic,
      malignant strictures. The parameters analyzed included presentation of patients,
      ascending urethrogram (AUG) and descending urethrogram findings, pre- and
      postoperative International prostate symptoms score (IPSS), uroflowmetry (Qmax),
      and post-void residue (PVR). Need for self calibration/ancillary procedures were
      assessed. Failure was defined as requirement for a subsequent endoscopic or open
      surgery. A urethral balloon catheter (Cook Urological, Spencer, Indiana) is
      passed over a guide wire after on table AUG and inflated till 180 psi for 5
      minutes under fluoroscopy till waist disappears. Dilatation is followed by
      insertion of a Foley catheter. Patients were followed up at 1, 3, and 6 months.
      RESULTS: Mean age was 49.86 years. Mean follow-up was 6 (2-60) months. IPSS
      improved from 21.6 preoperative to 5.6 postoperatively. Qmax increased from 5.7
      to 19.1 and PVR decreased from 90.2 to 28.8 (P < 0.0001*) postoperatively. At 1,
      3, and at 6 monthly follow-up, 69.2% (n = 82) patients were asymptomatic.
      CONCLUSIONS: Balloon dilation is a safe, well-tolerated procedure with minimal
      complications. Further randomized studies comparing balloon dilatation with
      direct internal visual urethrotomy are warranted.

PMID- 24311904
TI  - Rectal impalement with bladder perforation: A review from a single institution.
AB  - CONTEXT: Impalement injuries of the rectum with bladder perforation have been
      rarely reported. Such lesions have been associated with increased postoperative
      morbidity. A well-conducted preoperative evaluation of the lesions tends to
      prevent such complications. AIMS: To increase awareness about patients with
      rectal impalement that involve bladder injuries and to examine the significance
      of thorough clinical examination and complementary investigation for these
      patients' management. MATERIALS AND METHODS: Retrospectively, we identified three
      patients with rectal impalement and bladder perforation treated in University
      Hospital Hassan II, Fez, Morocco. We recorded the symptoms, subsequent
      management, and further follow-up for each patient. All available variables of
      published cases were reviewed and analyzed. RESULTS: Evident urologic symptoms
      were present in only one patient. Bladder perforation was suspected in two other
      patients on the basis of anterior rectal perforation in digital exam. Retrograde
      uroscanner could definitely confirm the diagnosis of bladder perforation. Fecal
      and urine diversion was the basis of the treatment. No postoperative
      complications were noted. We have reviewed 14 previous reports. They are
      presented mainly with urine drainage through the rectum. Radiologic investigation
      (retrograde cystography and retrograde uroscanner) confirmed bladder perforation
      in 10 patients (71.4%). Unnecessary laparotomy was performed in six patients
      (42.8%). Fecal diversion and urinary bladder decompression using urethral
      catheter were the most performed procedures in bladder perforation [6/14 patients
      (42.8%)]. No specific postoperative complications were reported. CONCLUSIONS: A
      high index of clinical suspicion is required to make the diagnosis of bladder
      perforation while assessing patients presenting with rectal impalement.
      Meticulous preoperative assessment is the clue of successful management.

PMID- 24311905
TI  - Penile autotransplantation in rats: An animal model.
AB  - CONTEXT: Penile allotransplantation might be a viable option for patients who
      need penile reconstruction. AIMS: A successful autotransplantation rat model is
      the first step toward proceeding for allotransplantation. We herein evaluate
      autotransplantation following transaction of the rat penis just distal to the
      urethral bulb. SETTINGS AND DESIGN: Experimental animal study. MATERIALS AND
      METHODS: Five Sprague-Dawely rats weighing 520 g (SD 19) were used. Utilizing a
      magnification of 6-40, transection and immediate anastomosis of the tunica
      albuginea, urethra, dorsal vein and nerves were carried out. Vesicostomy was made
      to divert urine. The glandular skin was sutured to the perineum and the abdominal
      wall was closed in layers. STATISTICAL ANALYSIS USED: Descriptive statistics.
      RESULTS: Average surgery time was 8 h. The first two rats had no vesicostomy and
      died in the first postoperative day from retention. Three rats tolerated well the
      procedure and survived to the end point. One rat was sacrificed at day 10 and
      histopathology showed 30-50% necrosis of the implanted penis. Another rat was
      sacrificed at day 20 and showed normal cavernous tissue. The fifth rat was
      sacrificed 3 months postoperatively and showed evidence of moderate corporal
      fibrosis. Urethral fistula and necrosis of corpus spongiosum, dorsal nerve
      necrosis and dorsal vein occurred in all animals. CONCLUSIONS: Penile
      autotransplantation in rats is feasible and provides the basis for evaluation of
      the corpora cavernosa in an allotransplantation model. Long-term urethral
      continuity and dorsal neurovascular bundle survival in this model is difficult to
      establish.

PMID- 24311906
TI  - Pre-prostatic tissue removed in robotic assisted lymph node dissection for
      prostate cancer contains lymph nodes.
AB  - OBJECTIVE: The on-going discussion about extent and best template for pelvic
      lymph dissection (PLND) motivated us to analyse pre-prostatic tissue (PPT) for
      lymph nodes and metastases. MATERIALS AND METHODS: From December 2010 to August
      2011 PPT was sent for histopathological evaluation during 80 robotic assisted
      radical prostatectomies (RARP) and one extended staging lymph node dissection.
      All patients had either a limited (lPLND, n = 44) or an extended lymph node
      dissection (ePLND, n = 36). Clinical data were retrospectively analyzed and
      compared to histopathological findings. RESULTS: Lymph nodes were found in PPT in
      10/80 (12.5%) patients after RARP and in the one patient after staging ePLND.
      Mean number of lymph nodes detected in PPT of them was 1.2 (range 1-3).
      Clinically no differences were found between patients with or without lymph nodes
      in PPT. In the standard template of either ePLND or lPLND the average number of
      lymph nodes was 13 (range 2-56). Herein metastases were found in 10 (12.5%)
      patients after RARP and in the patient after staging ePLND. A metastasis in PPT
      was only found after staging ePLND. CONCLUSIONS: Pre-prostatic tissue might
      contain lymph nodes that potentially harbour metastases. In the intention to
      perform the most accurate staging this tissue should be considered for
      histopathological evaluation.

PMID- 24311907
TI  - The effect of a 6 Fr catheter on flow rate in men.
AB  - BACKGROUND: The pressure-flow study (PFS) is considered the gold standard for the
      detection of bladder outlet obstruction (BOO) in men. However, several studies
      have raised the possibility that transurethral catheterization might have an
      obstructive effect on PFS while others did not. OBJECTIVES: To evaluate the
      effect of a 6 Fr transurethral catheter on the pressure-flow study and to
      evaluate its clinical implication in men. MATERIALS AND METHODS: A retrospective
      chart review study of 515 men referred for an evaluation of lower urinary tract
      symptoms and who underwent an urodynamic study (UDS). Of those, 133 met our
      inclusion/exclusion criteria. Non invasive free-flow studies (NIFFS) were
      performed before every UDS. Cystometrogram and PFS were performed through a 6 Fr
      transurethral catheter. RESULTS: The maximal flow rate (Qmax) was significantly
      higher (P < 0.001) in the NIFFS (15.0 mL/s (range 9.0-23.0)) than in the PFS
      (11.0 mL/s (range 7.0-18.5)). This difference became greater (18.5 mL/s (range
      10.0-30.3) vs. 13.0 mL/s (range 6.0-25.0), in favor of the NIFFS) when we
      analyzed only the patients (n = 34) who voided a similar volume. According to the
      International Continence Society (ICS) nomogram, the use of the PFS alone would
      have resulted in the upstaging of 14% of cases (10/71) in the overall population
      and 24% (4/17) in the sub-analyzed group. CONCLUSION: A 6 Fr transurethral
      catheter significantly lowers the maximal flow rate by 4 mL/s. Its presence
      resulted in an upstaging on the ICS nomogram. However, further studies will be
      necessary to confirm this upstaging.

PMID- 24311908
TI  - Evolutions of urodynamic studies: Toward less invasive and more physiological
      diagnostic tool.

PMID- 24311909
TI  - Interposition flaps in vesicovaginal fistula repairs can optimize cure rate.
AB  - AIM: To report the result of vesicovaginal fistula (VVF) repair using the
      transabdominal approach with flap interposition. MATERIALS AND METHODS: Between
      January 2004 and the end of 2011, operative reports data and medical records
      systems were reviewed for all VVF cases operated and followed in Urology
      Department. All patients had detailed history taking and physical exam followed
      by intravenous pyelograms or contrast CT abdomen and pelvis to rule out the
      presence of ureterovaginal fistulae. We utilized the infra-umbilical
      transabdominal approach and transpose an omental flap or peritoneal flap between
      the vaginal and bladder incisions in all cases. RESULTS: Twenty-six patients with
      an average age of 46 years were managed for VVF through transabdominal route with
      interposition of omental flap or peritoneal flap by a single surgeon. Twelve
      cases of VVF were secondary to lower segment cesarean section (LSCS) and twelve
      cases of VVF were secondary to lower segment cesarean section (LSCS) and 14 cases
      following hysterectomies. We had 16 complex VVF with 4 cases that failed the
      previous abdominal repair outside the hospital. More than 95% (25) of our
      patients were cured at the first attempt, with no recurrence at a mean follow-up
      of 28.6 (range 8-73) months. CONCLUSION: Successful repair of VVF depends on the
      experience of the surgeon and adhering to basic surgical principles. Very high
      success rate was seen when flap interposition had been used.

PMID- 24311910
TI  - Outcome of surgical management of non-palpable testes.
AB  - BACKGROUND: We reviewed the success rates of orchidopexies performed for non
      palpable testes at our institution and correlated preoperative and intraoperative
      findings to eventual outcomes. MATERIALS AND METHODS: We retrospectively reviewed
      ninty five medical records of patients who underwent laparoscopic exploration for
      the assessment of a non-palpable testes between 1996 and 2009. Intra-operative
      data for one hundrad eight non-palpable testes were collected. Operative success
      was defined as a testis comparable in size or slightly smaller than the contra
      lateral testis with normal consistency on the last follow-up. RESULTS: There were
      seventy (65%) viable testes at exploration, thirty one nubbins (29%) removed and
      7 (6%) absent. In the seventy six unilateral cases, contra-lateral hypertrophy
      was found in twinty five (33%) testes. Of which, twinty one (84%) were associated
      with absent testes or finding of a nubbin rather than a viable testis. In
      contrast, absent testes or finding of a nubbin was noted in 12 of 51 (23.5%)
      patients without contra-lateral hypertrophy. The difference was statistically
      significant (P < 0.001). Mean follow-up was seventeen months. Of the fifty testes
      in which the testicular artery was preserved, 7 were lost to follow-up and 3 of
      the remaining fourty three (7%) were atrophic. The twinty testes that underwent
      Fowler-Stephens orchidopexy (FSO) had a similar rate of atrophy, with only 1 (5%)
      atrophic testis identified following staged FSO (P > 0.83). INTERPRETATION:
      Testicular atrophy rate was similar in both artery sparing and Fowler-Stephens
      orchidopexies. Contra-lateral hypertrophy was significantly associated with
      absent testes or finding of a nubbin rather than a viable testis.

PMID- 24311911
TI  - Long-term outcome of genital reconstruction of Middle Eastern women with
      congenital adrenal hyperplasia.
AB  - OBJECTIVES: There is a paucity of data on the long-term outcome of genital
      reconstruction of female children with congenital adrenal hyperplasia (CAH) as
      they become adult women. We report on the surgical outcome general condition and
      marriage status. MATERIALS AND METHODS: We reviewed the medical records of women
      20 years or older with CAH who had genital reconstruction. We interviewed married
      patients utilizing the female sexual function index (FSFI-6) questionnaire and
      compared them to age-matched controls. RESULTS: We identified 43 women with CAH
      with a median age of 24.2 +/- 3.9 years and a median follow-up of 23.4 +/- 4.6
      years. Salt wasting and the severity of virilization affected most patients,
      parents were commonly cousins, children were reared as boys for a protracted
      period and surgical reconstruction was usually complex. Only five women had
      married. Compared with single women, married women had significantly more
      frequent normal menses, emergency hospital admissions and number of repeated
      reconstructive surgery. There was no significant difference in FSFI score between
      patients and controls. Four women conceived and three gave birth to one healthy
      child. There was no significant difference in the number of children between
      patients and controls. CONCLUSIONS: CAH has a significant impact on adult women
      in our region. Most of the patients remain single. Few women get married and
      these are able to lead a nearly normal sexual life and give birth to healthy
      children.

PMID- 24311912
TI  - Sarcomatoid carcinoma of prostate involving the whole lower urinary tract and
      rectum.
AB  - Sarcomatoid carcinoma of prostate is an extremely rare but aggressive neoplasm.
      It is generally associated with a poor prognosis. About 100 cases have so far
      been reported in the English literature. We report the case of a 64-year-old male
      with a very rapidly progressive disease that ultimately involved the whole lower
      urinary tract and rectum. The management of this case along with etio
      pathogenesis and literature review is discussed. 

PMID- 24311913
TI  - The unusual nested carcinoma of the renal pelvis.
AB  - Invasive urothelial carcinoma has a potential to show divergent differentiation.
      Several uncommon morphological variants have been described in the recent past.
      One such rare type is the nested variant of urothelial carcinoma. Most of the
      published reports depict occurrence of this variant in the urinary bladder. We
      report an unusual presentation of this uncommon entity in the renal pelvis of a
      54-year-old lady who presented with widespread skeletal metastases without any
      urinary symptoms. 

PMID- 24311914
TI  - Superior vena cava syndrome due to metastasis from urothelial cancer: A case
      report and literature review.
AB  - Superior vena cava (SVC) syndrome is caused by compression or obstruction of the
      SVC. We report here in a case of SVC syndrome due to lymph node metastasis from
      urothelial cancer to the mediastinum and lung. The origin of metastasis was
      determined by computed tomography (CT)-guided biopsy of metastases. After
      radiotherapy to the mediastinum with glucocorticoid failed, anticancer
      pharmacotherapy including paclitaxel, gemicitabine, and cisplatin proved
      effective and SVC syndrome resolved. But patient died from cerebral bleeding from
      newer brain metastases 10 months later. 

PMID- 24311915
TI  - Malignant superior vena cava syndrome.

PMID- 24311916
TI  - Prune belly syndrome with urethral hypoplasia and vesico-cutaneous fistula: A
      case report and review of literature.
AB  - Association between Prune belly syndrome (PBS) and urethral hypoplasia is an
      unusual condition. It is usually fatal unless there is a communication between
      the fetal bladder and the amniotic sac. We report a case of PBS with urethral
      hypoplasia and congenital vesico-cutaneous fistula in a male neonate. Patient
      underwent cutaneous vesicostomy and was discharged for close follow up of his
      renal function and for future reconstruction. 

PMID- 24311917
TI  - Renal cell carcinoma-associated adult dermatomyositis treated laparoscopic
      nephrectomy.
AB  - A 77-year-old female, who suffered from rheumatoid arthritis and hypothyroidism,
      developed severe muscle weakness. Clinical features, blood results and muscle
      biopsy suggested a possible diagnosis of dermatomyositis. A computed tomography
      of the chest, abdomen and pelvis showed a solid mass in the left kidney. She
      underwent a left laparoscopic nephrectomy and histology confirmed conventional
      (clear cell) renal cell carcinoma. She recovered slowly and almost back to normal
      life after 6 months. Early appreciation of the typical skin rash may provide a
      clue to the diagnosis and screening for neoplasm may improve prognosis. 

PMID- 24311918
TI  - Adrenal rests associated with ectopic testis in an adult: Clinical significance.
AB  - Ectopic adrenal tissue may be present along the path of the testis and discovered
      during groin surgery. The condition has been mainly reported in the pediatric
      population and very rarely in adults. Here, we report on the case of an adult
      male with undescended testis who received orchidectomy, and ectopic adrenal
      tissue was discovered in the removed specimen. The clinical significance of such
      a condition is discussed. 

PMID- 24311919
TI  - Genital self-amputation or the Klingsor syndrome: Successful non-microsurgical
      penile replantation.
AB  - Self-mutilations of the external genitals in psychiatric patients also known as
      Klingsor syndrome is a rare urologic trauma. Men with religious conflicts, low
      self-esteem, unresolved transsexual issues and feelings of guilt are the most
      vulnerable. This condition requires immediate surgical intervention. Currently
      replantation involves meticulous microsurgery and has become the primary method
      for managing these patients. In this paper, we report a case of self amputation
      of penis in a patient with a psychiatric history significant for schizopfrenia.
      Because of the unavailability of a microscope in our department, a non
      microsurgical replantation without microscopic magnification was attempted. After
      surgery, normal appearance and function including a good normal voiding,
      sensation, and erections were observed. 

PMID- 24311920
TI  - Primary localized amylodoisis of bladder: Is there a need for cystoscopic
      surveillance?
AB  - Amyloidosis is a heterogeneous group of disorders characterized by extracellular
      deposition of amorphous proteinaceous material in various tissues. Amyloidosis of
      bladder is of significant clinical interest to the urologist because of its
      presentation as urothelial cancer. Transurethral resection and histology
      examination is essential to exclude malignancy and to establish the benign nature
      of amyloidosis. Apart from managing the localized bladder amyloidosis, it is
      important to exclude systemic amyloidosis. Here in we describe two cases of
      localized, primary amyloidosis and discuss briefly their management and follow
      up. 

PMID- 24311921
TI  - Antibiotic resistance in Citrobacter spp. isolated from urinary tract infection.

PMID- 24311922
TI  - Citrobacter: An emerging health care associated urinary pathogen.

PMID- 24311923
TI  - Prevalence and risk factors for thyroid eye disease among Korean dysthyroid
      patients.
AB  - PURPOSE: To determine the prevalence of thyroid eye disease among dysthyroid
      Korean patients and to analyze the relationship between demographic data,
      lifestyle risk factors, and status of thyroid disease and thyroid eye disease.
      METHODS: All dysthyroid patients who visited endocrinology clinics in 24 general
      hospitals in Korea during a chosen one-week period were enrolled in this cross
      sectional study. Data were collected during an interviewer-administered
      questionnaire and chart review. Demographic data, lifestyle risk factors, and
      status of thyroid disease variables were analyzed as risk factors using
      multivariable regression models to identify independent associations with thyroid
      eye disease. RESULTS: A total of 1,632 dysthyroid patients were included (1,301
      females [79.7%] and 331 males [20.3%]). Two hundred eighty-three of these
      patients (17.3%) had thyroid eye disease. Multiple logistic regression analyses
      revealed that female gender, young age, Graves' disease, dermopathy, anti-thyroid
      medication treatment, and radioiodine treatment were independent risk factors for
      thyroid eye disease. CONCLUSIONS: The lower prevalence of thyroid eye disease in
      dysthyroid Korean patients and the influence of gender on risk factors in this
      study are novel findings compared to studies performed involving Europeans.
      Although the risk factors for thyroid eye disease are understood in part, a more
      in-depth comparative study of gender and ethnic groups is needed to fully
      understand the biological significance of the demographic factors.

PMID- 24311924
TI  - The efficacy of the combined procedure in involutional entropion surgery: a
      comparative study.
AB  - PURPOSE: To evaluate the efficacy of the combined procedure in the management of
      involutional entropion. METHODS: In this study, we reviewed 45 eyes of 36
      patients who underwent the combined procedure (lateral tarsal strip, retractor
      tightening, and everting sutures) for the management of involutional lower eyelid
      entropion and compared the results with 31 eyes of 25 patients who underwent the
      Wies procedure. Exclusion criteria included previous lower eyelid surgery and
      follow-up of less than 6 months. RESULTS: No patients demonstrated entropion on
      the first postoperative day. The mean follow-up period was 18.4 months (6 to 52
      months) in the Wies group and 22.6 months (6 to 59 months) in the combined
      procedure group. During the follow-up period, 9 of 31 eyes in the Wies group
      presented with recurrence and only 1 of 45 eyes in the combined procedure group
      presented with recurrence (p = 0.001). The average time of recurrence was 4.8
      months in the Wies group. Recurrence occurred at 2 months postoperatively in the
      patient in the combined procedure group. Six of the 9 recurrences in the Wies
      group were managed by the combined procedure. None of these patients had further
      recurrence after correction. Three patients complained about a visible incision
      line after the Wies procedure. CONCLUSIONS: The combined procedure seems to be
      more effective than the Wies procedure in the management of involutional
      entropion. The combined procedure addresses the three major causative factors in
      involutional entropion and makes it possible to perform the surgery using a small
      incision.

PMID- 24311925
TI  - Long-term evaluation of endothelial cell changes in Fuchs corneal dystrophy: the
      influence of phacoemulsification and penetrating keratoplasty.
AB  - PURPOSE: To evaluate the natural course of the long-term endothelial cell changes
      in Fuchs corneal dystrophy (FCD) patients and investigate the effects of
      phacoemulsification on the annual rate of change in endothelial indices in FCD
      patients. METHODS: Thirty-four patients diagnosed with FCD at Seoul National
      University Hospital from 1994 to 2010 were retrospectively reviewed. Sixteen
      patients who had been followed up for more than 1 year were selected and
      classified into 3 groups: group A, patients with no ocular surgery; group B,
      patients who had undergone phacoemulsification only; and group C, patients who
      had undergone penetrating keratoplasty with cataract surgery. Endothelial cell
      density, polymegethism, pleomorphism, and pachymetry were measured and the
      exponential rates of endothelial cell and pachymetry change were analyzed.
      RESULTS: A non-linear mixed model of non-operated FCD patients showed that only
      pachymetric data tended to increase with statistical significance (p = 0.001)
      with a mean follow-up period of 4.15 years. Using an exponential regression
      analysis fitting curve, the mean rates of annual endothelial cell loss were
      0.82%/yr, 20.39%/yr, and 29.27%/yr in groups A, B, and C respectively, and
      statistical significance was seen only in group C (p < 0.05). CONCLUSIONS:
      Retrospective long-term follow-up data showed that changes in endothelial density
      did not significantly decrease over at least 4 years in middle-aged FCD patients.
      The changes in pachymetric corneal thickness appeared to increase over the same
      period. Considering that no exponential changes were aggravated after performing
      cataract surgery alone, cataract surgery would be a preferable option in FCD
      patients compared to an approach of "wait-and-do" penetrating keratoplasty
      combined with cataract surgery.

PMID- 24311926
TI  - The pathologic characteristics of pingueculae on autofluorescence images.
AB  - PURPOSE: To analyze the autofluorescence (AF) properties of pinguecula using
      cobalt-blue and yellow filters and to investigate the nature and pathogenesis of
      pingueculae using histochemical and immunohistochemical staining. METHODS: Fifty
      pingueculae in 40 patients were included in this study. AF of the pingueculae was
      observed and analyzed using a cobalt-blue filter with an additional yellow filter
      on a slit-lamp. Hematoxylin-eosin and immunohistochemical stainings were
      performed on surgical specimens of pingueculae that were prepared from each
      patient. Immunohistochemical staining included Congo red, Oil Red O, periodic
      acid-Schiff (PAS), Masson's trichrome, transglutaminase-2 (TG-2), mesenchymal
      stem cell markers CD29 (beta-1-integrin), and CD34. RESULTS: AF images revealed
      hyper-AF in the pinguecula area. The AF lesions of pingueculae showed superficial
      punctuate erosions and avascular lesions. Deposition of eosinophilic and
      amorphous materials in the subepithelial layer of the pinguecula were observed on
      hematoxylin-eosin staining. Historeactivities to Congo red, PAS, Oil Red O,
      alcian blue, and Masson's trichrome were not detected, but immunoreactivities to
      CD29, CD34, and TG-2 were detected in the pingueculae with AF. However, CD29,
      CD34, and TG-2 were not detected in the pingueculae without AF. CONCLUSIONS: The
      AF of pingueculae may be related to CD29, CD34, and TG-2. We suggest that
      pingueculae with AF have a different pathogenesis compared to pingueculae without
      AF.

PMID- 24311927
TI  - The correlation between angle kappa and ocular biometry in Koreans.
AB  - PURPOSE: To investigate normative angle kappa data and to examine whether
      correlations exist between angle kappa and ocular biometric measurements (e.g.,
      refractive error, axial length) and demographic features in Koreans. METHODS:
      Data from 436 eyes (213 males and 223 females) were analyzed in this study. The
      angle kappa was measured using Orbscan II. We used ocular biometric measurements,
      including refractive spherical equivalent, interpupillary distance and axial
      length, to investigate the correlations between angle kappa and ocular biometry.
      The IOL Master ver. 5.02 was used to obtain axial length. RESULTS: The mean
      patient age was 57.5 +/- 12.0 years in males and 59.4 +/- 12.4 years in females
      (p = 0.11). Angle kappa averaged 4.70 +/- 2.70 degrees in men and 4.89 +/- 2.14
      degrees in women (p = 0.48). Axial length and spherical equivalent were
      correlated with angle kappa (r = -0.342 and r = 0.197, respectively). The
      correlation between axial length and spherical equivalent had a negative
      correlation (r = -0.540, p < 0.001). CONCLUSIONS: Angle kappa increased with
      spherical equivalent and age. Thus, careful manipulation should be considered in
      older and hyperopic patients when planning refractive or strabismus surgery.

PMID- 24311928
TI  - Anti-VEGF-refractory exudative age-related macular degeneration: differential
      response according to features on optical coherence tomography.
AB  - PURPOSE: To describe optical coherence tomography (OCT) characteristics of
      neovascular age-related macular degeneration (AMD) patients refractory to
      intravitreal anti-vascular endothelial growth factor (VEGF) injections
      (ranibizumab, bevacizumab) and their responses to alternative anti-VEGF agents or
      photodynamic therapy (PDT). METHODS: A retrospective review of 267 neovascular
      AMD patients treated with intravitreal anti-VEGF injections. RESULTS: Twenty
      patients (7.5%) were refractory to anti-VEGF injections (stationary or increased
      retinal exudation despite three or more monthly injections). They were grouped
      into either the extensive intraretinal fluid group (IRF group, 9 patients) or the
      subretinal fluid only group (SRF group, 11 patients) according to OCT findings.
      In the IRF group, response rates to subsequent treatment were 0% (0 / 7) for
      bevacizumab, 50% (3 / 6) for ranibizumab and 50% (3 / 6) for PDT +/- anti-VEGF.
      Three out of four bevacizumab-refractory patients showed response to ranibizumab
      as a secondary treatment. In the SRF group, response rates were lower with 0% (0
      / 7) for bevacizumab, 22.2% (2 / 9) for ranibizumab and 28.6% (2 / 7) for PDT +/-
      anti-VEGF. One out of four bevacizumab-refractory patients responded to
      ranibizumab. The visual outcome was worse in the IRF group (median 20 / 1,000)
      than in the SRF group (median 20 / 100). CONCLUSIONS: In anti-VEGF-refractory
      neovascular AMD, patients with extensive IRF refractory to bevacizumab can be
      responsive to ranibizumab while patients with SRF may be refractory to both,
      suggesting a different pathophysiology and intraocular pharmacokinetics.

PMID- 24311929
TI  - Comparison of choroidal thickness in patients with diabetes by spectral-domain
      optical coherence tomography.
AB  - PURPOSE: To evaluate choroidal thickness in diabetes patients using spectral
      domain optical coherence tomography. METHODS: We examined 203 eyes of 203
      diabetic participants and 48 eyes of 48 healthy controls. The choroidal thickness
      at the foveal lesion was measured by enhanced-depth imaging optical coherence
      tomography. The participants were grouped according to diabetic retinopathy
      grade: no diabetic change, mild-to-moderate or severe non-proliferative, or
      proliferative diabetic retinopathy. The study parameters included history, age,
      axial length, intraocular pressure, central retinal thickness, fasting glucose,
      and blood pressure. RESULTS: The subfoveal choroidal thickness was thinner in
      eyes with non-proliferative or proliferative diabetic retinopathy than in normal
      eyes (p < 0.01). However, there was no difference between eyes with non
      proliferative and proliferative diabetic retinopathy or between eyes with no
      diabetic change and the controls. Eyes exhibiting macular edema showed no
      significant difference in choroidal thickness compared with eyes having normal
      macular contours. CONCLUSIONS: The central choroid is thinner when eyes show
      diabetic changes on the retina. However, the presence of diabetic macular edema
      or proliferative change is not associated with more pronounced choroidal
      thinning.

PMID- 24311930
TI  - Comparison between glaucomatous and non-glaucomatous eyes with unilateral retinal
      vein occlusion in the fellow eye.
AB  - PURPOSE: To evaluate and compare the clinical and angiographic characteristics of
      retinal vein occlusion (RVO) in glaucomatous and non-glaucomatous eyes with
      unilateral RVO in the fellow eye. METHODS: Twenty-one glaucomatous eyes (GL
      group) and 25 age-matched non-glaucomatous eyes (non-GL group) with unilateral
      RVO in the fellow eye were included in this study. Fluorescein angiographic
      images were assessed in both groups by 3 retina specialists in order to determine
      the RVO occlusion site. The occlusion site was divided into 2 types:
      arteriovenous (AV)-crossing and non-AV-crossing (optic cup or optic nerve sited).
      The clinical characteristics and prevalence of AV-crossing and non-AV-crossing
      RVO were compared between the 2 groups. RESULTS: The mean baseline intraocular
      pressures of the RVO eye and the fellow eye did not differ between the 2 groups
      (RVO eye: 14.3 +/- 2.5 mmHg [non-GL group], 15.5 +/- 3.9 mmHg [GL group], p =
      0.217; fellow eye: 14.4 +/- 2.5 mmHg [non-GL group], 15.7 +/- 3.7 mmHg [GL
      group], p = 0.148). The prevalence of systemic disease did not differ between the
      2 groups (e.g., diabetes mellitus and hypertension, p = 0.802 and 0.873,
      respectively). AV-crossing RVO was significantly more frequent in the non-GL
      group (19 eyes; 76%) than in the GL group (4 eyes, 19%, p < 0.001). CONCLUSIONS:
      Non-AV-crossing RVO, i.e., optic cup- or optic nerve-sited RVO, is more
      frequently associated with glaucomatous changes in the fellow eye. Therefore,
      this type of RVO should be monitored more carefully for indications of glaucoma
      in the fellow eye.

PMID- 24311931
TI  - In vitro effects of preservative-free and preserved prostaglandin analogs on
      primary cultured human conjunctival fibroblast cells.
AB  - PURPOSE: Long-term use of topical medication is needed for glaucoma treatment.
      One of the most commonly prescribed classes of hypotensive agents are
      prostaglandin analogs (PGs) used as both first-line monotherapy; as well as in
      combination therapy with other hypotensive agents. Several side effects of eye
      drops can be caused by preservatives. The purpose of this study was to evaluate
      the effects of PGs with varying concentrations of benzalkonium chloride (BAC),
      alternative preservatives, or no preservatives on human conjunctival fibroblast
      cells. METHODS: Primary human conjunctival fibroblast cells were used in these
      experiments. Cells were exposed to the following drugs: BAC at different
      concentrations, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC
      0.02%), tafluprost 0.0015% with/without 0.001% BAC and travoprost 0.004% (with
      0.001% Polyquad) for 15 and 30 minutes. Cell cytotoxicity was evaluated by phase
      contrast microscopy to monitor morphological changes of cells, Counting Kit-8
      (CCK-8) assay to cell viability, and fluorescent activated cell sorting (FACS)
      analysis to measure apoptosis. RESULTS: BAC caused cell shrinkage and detachment
      from the plate in a dose-dependent manner. Morphological changes were observed in
      cells treated with bimatoprost 0.01% and latanoprost 0.005%. However, mild cell
      shrinkage was noted in cells treated with tafluprost 0.0015%, while a non-toxic
      effect was noted with travoprost 0.004% and preservative-free tafluprost 0.0015%.
      CCK-8 assay and FACS analysis showed all groups had a significantly decreased
      cell viability and higher apoptosis rate compared with the control group.
      However, travoprost 0.004% and preservative-free tafluprost 0.0015% showed lower
      cytotoxicity and apoptosis rate than other drugs. CONCLUSIONS: This in vitro
      study revealed that BAC-induced cytotoxicity is dose-dependent, although it is
      important to emphasize that the clinical significance of toxicity differences
      observed among the different PGs formulations has not yet been firmly
      established. Alternatively preserved or preservative-free glaucoma medications
      seem to be a reasonable and viable alternative to those preserved with BAC.

PMID- 24311932
TI  - A case of Korean patient with macular corneal dystrophy associated with novel
      mutation in the CHST6 gene.
AB  - To report a novel mutation within the CHST6 gene, as well as describe light and
      electron microscopic features of a case of macular corneal dystrophy. A 59-year
      old woman with macular corneal dystrophy in both eyes who had decreased visual
      acuity underwent penetrating keratoplasty. Further studies including light and
      electron microscopy, as well as DNA analysis were performed. Light microscopy of
      the cornea revealed glycosaminoglycan deposits in the keratocytes and endothelial
      cells, as well as extracellularly within the stroma. All samples stained
      positively with alcian blue, colloidal iron, and periodic acid-Schiff. Electron
      microscopy showed keratocytes distended by membrane-bound intracytoplasmic
      vacuoles containing electron-dense fibrillogranular material. These vacuoles were
      present in the endothelial cells and between stromal lamellae. Some of the
      vacuoles contained dense osmophilic whorls. A novel homozygous mutation (c.613
      C>T [p.Arg205Trp]) was identified within the whole coding region of CHST6. A
      novel CHST6 mutation was detected in a Korean macular corneal dystrophy patient. 

PMID- 24311933
TI  - Self-inflicted chronic bacterial keratoconjunctivitis using self semen.
AB  - This case report describes a case of self-inflicted chronic bacterial
      keratoconjunctivitis involving the patient's own semen. A 20-year-old male
      soldier was referred to our clinic for the evaluation of refractory chronic
      bacterial conjunctivitis. Over the previous 4 months, he had been treated for
      copious mucous discharge, conjunctival injection, and superficial punctate
      keratitis in both eyes at an army hospital and a local eye clinic. Despite the
      use of topical and systemic antibiotics according to the results of conjunctival
      swab culture, there was no improvement. During the repeated smear and culture of
      conjunctival swabs, surprisingly, a few sperm were detected on Gram staining,
      revealing that the condition was self-inflicted bacterial keratoconjunctivitis
      involving the patient's own semen. Thus, in cases of chronic keratoconjunctivitis
      that do not respond to appropriate antibiotic treatment, self-inflicted disease
      or malingering should be considered. 

PMID- 24311934
TI  - Free-floating vitreous cyst in an adult male.
AB  - A 50 year-old male patient was referred to our clinic due to a floating mass in
      the right eye. The uncorrected visual aquity was 10 / 10 in both eyes.The patient
      did not have any systemic disorder and trauma history. His ophthalmological
      examination revealed an unremarkable anterior segment with no signs of
      inflammation. Indirect opthalmoscopy and posterior segment biomicroscopy
      performed with 90D lens was unremarkable in the left eye, while in the right eye
      a single oval cyst was identified floating freely in the vitreous. The cyst was
      partially masking the underlying retinal vasculature. B-scan ultrasound revealed
      an echo-free, round-shaped cyst that was free from surrounding vitreous strands
      or retina localised at the posterior vitreous. Fluorescein angiography (FA) ruled
      out the presence of intra and overlying vascularisation of the cyst. Indeed, FA
      showed a clear-edged hypofluorescence due to a pre-retinal masking effect. The
      indirect hemaglutinin tests of the patient for ecinococcus and cysticercosis were
      negative. Eosinophilia was not detected in the preripheral blood smear. Based on
      these findings the patient was diagnosed as primary vitreal cyst. The presented
      case was mild symptomatic so the patient was decided to be followed up without
      any treatment. 

PMID- 24311935
TI  - Frosted branch angiitis as ocular manifestation of Behcet's disease: unusual case
      report and literature review.
AB  - We report an unusual case of unilateral frosted branch angiitis associated with
      Behcet's disease, including a review of previously reported cases. A 39-year-old
      male with history of recurrent oral and genital ulcers presented with visual loss
      in his left eye. Fundus findings demonstrated occlusive retinal vasculitis
      resembling acute frosted branch angiitis. Laboratory examinations including viral
      markers revealed no abnormal findings except positive HLA-B51. The patient was
      treated with systemic steroid and cyclosporine. Six months after presentation,
      new oral ulcers and pseudofolliculitis appeared, and he was diagnosed with
      Behcet's disease following rheumatology consultation. During follow-up, there was
      no change in visual acuity of hand movement, and disc neovascularization
      developed even after complete panretinal photocoagulation. Ocular manifestations
      of Behcet's disease can present as unilateral frosted branch angiitis, and may
      consecutively involve in both eyes. Early immunosuppressive treatment is
      recommended. 

PMID- 24311936
TI  - Ophthalmic artery aneurysm: potential culprit of central retinal artery
      occlusion.
AB  - Central retinal artery occlusion (CRAO) is one of the most devastating ophthalmic
      emergencies, causing acute painless visual loss in the affected eye. We describe
      the first case of acute non-arteritic CRAO associated with peripheral ophthalmic
      artery aneurysm and its clinical course after intra-arterial thrombolysis
      therapy. This case suggests that ophthalmic artery aneurysm can be the cause of
      CRAO and should be included in the differential diagnosis of CRAO. 

PMID- 24311937
TI  - Horner's syndrome and contralateral abducens nerve palsy associated with zoster
      meningitis.
AB  - A 55-year-old woman presented with diplopia following painful skin eruptions on
      the right upper extremity. On presentation, she was found to have 35 prism
      diopters of esotropia and an abduction limitation in the left eye. Two weeks
      later, she developed blepharoptosis and anisocoria with a smaller pupil in the
      right eye, which increased in the darkness. Cerebrospinal fluid analysis showed
      pleocytosis and a positive result for immunoglobulin G antibody to varicella
      zoster virus. She was diagnosed to have zoster meningitis with Horner's syndrome
      and contralateral abducens nerve palsy. After intravenous antiviral and steroid
      treatments, the vesicular eruptions and abducens nerve palsy improved. Horner's
      syndrome and diplopia resolved after six months. Here we present the first report
      of Horner's syndrome and contralateral abducens nerve palsy associated with
      zoster meningitis. 

PMID- 24311938
TI  - Evaluating a Culturally Competent Health Coach Intervention for Chinese American
      Patients with Diabetes.

PMID- 24311939
TI  - Promoting Children's Social-Emotional Skills in Preschool Can Enhance Academic
      and Behavioral Functioning in Kindergarten: Findings from Head Start REDI.
AB  - This study examined processes of change associated with the positive preschool
      and kindergarten outcomes of children who received the Head Start REDI
      intervention, compared to "usual practice" Head Start. In a large-scale
      randomized-controlled trial (N = 356 children, 42% African American or Latino,
      all from low-income families), this study tests the logic model that improving
      preschool social-emotional skills (e.g., emotion understanding, social problem
      solving, and positive social behavior) as well as language/emergent literacy
      skills will promote cross-domain academic and behavioral adjustment after
      children transition into kindergarten. Validating this logic model, the present
      study finds that intervention effects on three important kindergarten outcomes
      (e.g., reading achievement, learning engagement, and positive social behavior)
      were mediated by preschool gains in the proximal social-emotional and
      language/emergent literacy skills targeted by the REDI intervention. Importantly,
      preschool gains in social-emotional skills made unique contributions to
      kindergarten outcomes in reading achievement and learning engagement, even after
      accounting for the concurrent preschool gains in vocabulary and emergent literacy
      skills. These findings highlight the importance of fostering at-risk children's
      social-emotional skills during preschool as a means of promoting school
      readiness. The REDI (Research-Based, Developmentally-Informed) enrichment
      intervention was designed to complement and strengthen the impact of existing
      Head Start programs in the dual domains of language/emergent literacy skills and
      social-emotional competencies. REDI was one of several projects funded by the
      Interagency School Readiness Consortium, a partnership of four federal agencies
      (the National Institute of Child Health and Human Development, the Administration
      for Children and Families, the Assistant Secretary for Planning and Evaluation in
      the Department of Health and Human Services, and the Office of Special Education
      and Rehabilitation Services in the Department of Education). The projects funded
      through this partnership were designed to assess how integrative early
      interventions for at-risk children could promote learning and development across
      multiple domains of functioning. In addition, the projects were charged with
      examining processes of change and identifying mechanisms of action by which the
      early childhood interventions fostered later school adjustment and academic
      achievement. This study examined such processes of change, with the goal of
      documenting hypothesized cross-domain influences on kindergarten outcomes. In
      particular, this study tested whether gains in the proximal language/emergent
      literacy and social-emotional competencies targeted during Head Start would
      mediate the REDI intervention effects on kindergarten academic and behavioral
      outcomes. In addition, it tested the hypothesis that gains in social-emotional
      competencies during preschool would make unique contributions to intervention
      effects on both academic and behavioral outcomes, even after accounting for the
      effects of preschool gains in language and emergent literacy skills.

PMID- 24311940
TI  - Impact of a Gender-Transformative HIV and Antiviolence Program on Gender
      Ideologies and Masculinities in Two Rural, South African Communities.
AB  - "One Man Can" (OMC) is a rights-based gender equality and health program
      implemented by Sonke Gender Justice Network (Sonke) in South Africa. The program
      seeks to reduce the spread and impact of HIV and AIDS and reduce violence against
      women and men. To understand how OMC workshops impact masculinities, gender
      norms, and perceptions of women's rights, an academic/non-governmental
      organization (NGO) partnership was carried out with the University of Cape Town,
      the University of California at San Francisco, and Sonke. Sixty qualitative, in
      depth interviews were carried out with men who had completed OMC workshops and
      who were recruited from Sonke's partner organizations that were focused on gender
      and/or health-related services. Men were recruited who were over age 18 and who
      participated in OMC workshops in Limpopo and Eastern Cape Provinces, South
      Africa. Results reveal how men reconfigured notions of hegemonic masculinity both
      in terms of beliefs and practices in relationships, households, and in terms of
      women's rights. In the conclusions, we consider the ways in which the OMC program
      extends public health research focused on masculinities, violence, and HIV/AIDS.
      We then critically assess the ways in which health researchers and practitioners
      can bolster men's engagement within programs focused on gender equality and
      health.

PMID- 24311941
TI  - Drugs in development for treatment of patients with cancer-related anorexia and
      cachexia syndrome [Retraction].

PMID- 24311942
TI  - Development of PLGA-based itraconazole injectable nanospheres for sustained
      release.
AB  - PURPOSE: Itraconazole (ITZ) is a synthetic triazole antifungal agent, which is
      widely used for treatment and prevention of fungal infections. The purpose of
      this study is to develop ITZ-loaded poly(lactic-co-glycolic acid) (PLGA)
      nanospheres (PLGA-ITZ-NS) as a new sustained-release formulation for intravenous
      ITZ administration. MATERIALS AND METHODS: PLGA-ITZ-NS were prepared by a
      nanoprecipitation method and optimized by modifying the surfactant poloxamer 188
      concentration and PLGA:ITZ ratio. Their physicochemical properties, including
      size, zeta potential, external morphology and encapsulation efficiency, were
      characterized by dynamic light scattering (DLS), scanning electron microscopy
      (SEM) and high performance liquid chromatography (HPLC). The effect of the
      different selected lyoprotectants with various concentrations on NS particles
      size and surface charge were also assessed. Rapid and sensitive HPLC and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed to
      determine ITZ concentrations in formulation and in rat plasma, respectively.
      Pharmacokinetics of the optimum PLGA-ITZ-NS formulation was compared with the
      former commercial Sporanox(r) injection formulation using rats as the animal
      model. Noncompartmental pharmacokinetic parameters were obtained by WinNonlin(r)
      software. RESULTS: Optimal PLGA-ITZ-NS had a mean particle size of about 200 nm
      with a high homogeneity (polydispersity index ~0.2), favorable zeta potential
      (approximately -20 to -30 mV) and encapsulation efficiency (72%). In addition, 2%
      w/v sucrose was selected as a lyoprotectant for NS freeze-drying. The newly
      developed LC-MS/MS assay was validated and found to be accurate and precise. The
      in vivo study showed that the NS formulation has a similar systemic
      bioavailability to Sporanox(r) while providing a sustained plasma level (> 100
      ng/mL) for up to 24 hours after intravenous administration. CONCLUSION: Our newly
      developed PLGA-ITZ-NS has shown great sustained release and comparable
      bioavailability with Sporanox(r), therefore having the potential to be an
      alternative injectable formulation of ITZ.

PMID- 24311943
TI  - Target volume and position variations during intensity-modulated radiotherapy for
      patients with nasopharyngeal carcinoma.
AB  - PURPOSE: Considerable anatomical changes occur during intensity-modulated
      radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to
      quantify volumetric and positional variations of the target volume during IMRT.
      MATERIALS AND METHODS: Twenty patients with locally advanced NPC who received
      concurrent (13 patients) or sequential (seven patients) chemoradiotherapy were
      prospectively recruited and underwent planning computed tomography (CT) and six
      repeat CTs (every five fractions). Each repeat CT was rigidly registered to the
      planning CT. Gross tumor volume (GTV) and elective clinical target volume (CTV)
      were manually delineated on each axial CT image. CTVs of the primary tumor and
      lymph nodes were expanded with 5 mm margins to corresponding GTVs, with necessary
      modifications. Volume loss, system and random errors, and the mean and three
      dimensional vector displacements were calculated and compared statistically.
      RESULTS: Volumes of the primary tumor and small (>1 cm, <=3 cm) and large (>3 cm)
      positive neck lymph nodes decreased at a rate of 2.6%, 3.7%, and 3.9% per
      treatment day, respectively. CTVs of the primary tumor, lymph nodes, and elective
      region decreased 1.5%, 2.3%, and 0.3% per treatment day, respectively. Average
      displacements of the GTVs and CTVs were <1.3 mm in all directions. GTVs and CTVs
      of the large and small lymph nodes shifted medially by 0.8-1.3 and 0.6-1.2 mm,
      respectively, on average. Average three-dimensional displacements of the GTVs and
      CTVs were 3.4-4.3 mm and 2.5-3.7 mm, respectively. Volume loss and displacements
      in most directions were significantly larger in patients receiving concurrent
      chemoradiotherapy than in those receiving sequential therapy. Volume loss and
      displacements of the GTV of large nodes and elective CTV were significantly
      larger in male than in female patients. CONCLUSION: Volumetric and positional
      changes of the target volume were considerable, and volume loss increased as
      treatment time elapsed during IMRT for NPC.

PMID- 24311944
TI  - Multimodal cancer care research.

PMID- 24311945
TI  - An interprofessional palliative care oncology rehabilitation program: effects on
      function and predictors of program completion.
AB  - BACKGROUND: After treatment, patients with active cancer face a considerable
      burden from the effects of both the disease and its treatment. The Palliative
      Rehabilitation Program (prp) is designed to ameliorate disease effects and to
      improve the patient's functioning. The present study evaluated predictors of
      program completion and changes in functioning, symptoms, and well-being after the
      program. METHODS: The program received referrals for 173 patients who had
      finished anticancer therapy. Of those 173 patients, 116 with advanced cancer were
      eligible and enrolled in the 8-week interprofessional prp; 67 completed it.
      Measures of physical, nutritional, social, and psychological functioning were
      evaluated at entry to the program and at completion. RESULTS: Participants
      experienced significant improvements in physical performance (p < 0.000),
      nutrition (p = 0.001), symptom severity (p = 0.005 to 0.001), symptom
      interference with functioning (p = 0.003 to 0.001), fatigue (p = 0.001), and
      physical endurance, mobility, and balance or function (p = 0.001 to 0.001).
      Reasons that participants did not complete the prp were disease progression,
      geographic inaccessibility, being too well (program not challenging enough),
      death, and personal or unknown reasons. A normal level of C-reactive protein (<10
      mg/L, p = 0.029) was a predictor of program completion. CONCLUSIONS: Patients
      living with advanced cancers who underwent the interprofessional prp experienced
      significant improvement in functioning across several domains. Program completion
      can be predicted by a normal level of C-reactive protein.

PMID- 24311946
TI  - A prospective evaluation of an interdisciplinary nutrition-rehabilitation program
      for patients with advanced cancer.
AB  - BACKGROUND: Cancer can affect many dimensions of a patient's life, and in turn,
      it should be targeted using a multimodal approach. We tested the extent to which
      an interdisciplinary nutrition-rehabilitation program can improve the well-being
      of patients with advanced cancer. METHODS: Between January 10, 2007, and
      September 29, 2010, 188 patients with advanced cancer enrolled in the 10-12-week
      program. Body weight, physical function, symptom severity, fatigue dimensions,
      distress level, coping ability, and overall quality of life were assessed at the
      start and end of the program. RESULTS: Of the enrolled patients, 70% completed
      the program. Patients experienced strong improvements in the physical and
      activity dimensions of fatigue (effect sizes: 0.8-1.1). They also experienced
      moderate reductions in the severity of weakness, depression, nervousness,
      shortness of breath, and distress (effect sizes: 0.5-0.7), and moderate
      improvements in Six Minute Walk Test distance, maximal gait speed, coping
      ability, and quality of life (effect sizes: 0.5-0.7) Furthermore, 77% of patients
      either maintained or increased their body weight. CONCLUSIONS: Interdisciplinary
      nutrition-rehabilitation can be advantageous for patients with advanced cancer
      and should be considered an integrated part of standard palliative care.

PMID- 24311947
TI  - Publication patterns of cancer cost-effectiveness studies presented at major
      conferences.
AB  - OBJECTIVE: To be useful to policymakers and stakeholders, cost-effectiveness
      analyses (ceas) should be published in a timely manner and without bias. The aims
      of the present study were to examine the time between conference abstract
      presentation and subsequent publication, to determine the factors associated with
      time to publication, to evaluate potential publication bias, and to examine
      discrepancies in the results between abstract and publication. METHODS: Abstracts
      of ceas presented at the annual meetings of the American Society of Clinical
      Oncology (asco), the American Society of Hematology (ash), and the International
      Society for Pharmacoeconomics and Outcomes Research (ispor) between 1997 and 2007
      were reviewed. Time-to-event analysis was performed to assess the timeliness of
      publication and to examine factors associated with time to publication. Summary
      statistics were used to assess discrepancies in incremental cost-effectiveness
      ratios (icers) between abstract and publication. RESULTS: Of 164 abstracts
      identified, 65 (39.6%) were subsequently published. The 1-, 2-, 3-, and 5-year
      publication rates were 12.8%, 25%, 34.2%, and 40.5% respectively. Abstracts were
      more likely to be published if presented at asco than at ispor (hazard ratio:
      1.94; p = 0.038). There was no direct evidence of publication bias for abstracts
      with favourable icers. Comparing icers between abstracts and publications, the
      mean absolute difference was 23.8%; 50% of studies had a change in icer exceeding
      10%. CONCLUSIONS: Publication rates for ceas were low, and publication was not
      timely with respect to informing the decision-making process for funding.
      Abstract results often differed from publication results and cannot reliably be
      used in the decision-making process for funding.

PMID- 24311948
TI  - Panitumumab monotherapy compared with cetuximab and irinotecan combination
      therapy in patients with previously treated KRAS wild-type metastatic colorectal
      cancer.
AB  - BACKGROUND: The survival benefit for single-agent anti-epidermal growth factor
      receptor (egfr) therapy compared with combination therapy with irinotecan in KRAS
      wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line
      treatment setting is not known. The objective of the present study was to
      describe the characteristics of, and to compare survival outcomes in, two cohorts
      of patients treated with either singleagent panitumumab or combination therapy
      with cetuximab and irinotecan. METHODS: The study enrolled patients with KRAS wt
      mcrc previously treated with both irinotecan and oxaliplatin who had received
      either panitumumab or combination cetuximab-irinotecan before April 1, 2011, at
      the BC Cancer Agency (bcca). Patients were excluded if they had received anti
      egfr agents in earlier lines of therapy. Data were prospectively collected,
      except for performance status (ps), which was determined by chart review.
      Information about systemic therapy was extracted from the bcca Pharmacy Database.
      RESULTS: Of 178 eligible patients, 141 received panitumumab, and 37 received
      cetuximab-irinotecan. Compared with patients treated with cetuximab-irinotecan,
      panitumumab-treated patients were significantly older and more likely to have an
      Eastern Cooperative Oncology Group (ecog) ps of 2 or 3 (27.7% vs. 2.7%, p =
      0.001). Other baseline prognostic variables and prior and subsequent therapies
      were similar. Median overall survival was 7.7 months for the panitumumab group
      and 8.3 months for the cetuximab-irinotecan group. Multivariate analysis
      demonstrated that survival outcomes were similar regardless of the therapy
      selected (hazard ratio: 1.28; p = 0.34). An ecog ps of 2 or 3 compared with 0 or
      1 was the only significant prognostic factor in this treatment setting (hazard
      ratio: 3.37; p < 0.01). CONCLUSIONS: Single-agent panitumumab and cetuximab
      irinotecan are both reasonable third-line treatment options, with similar
      outcomes, for patients with chemoresistant mcrc.

PMID- 24311949
TI  - Positron-emission tomography for locally advanced cervical cancer: a survey
      assessing Canadian practice patterns and access.
AB  - PURPOSE: Imaging by fluorodeoxyglucose positron-emission tomography (pet) has
      emerged as a valuable tool in the management of locally advanced cervical cancer
      (lacc), both for assessment of lymph node status and determination of response to
      chemoradiotherapy. The aim of the present study was to survey Canadian radiation
      oncologists to determine access to pet imaging for lacc patients and to assess
      current patterns of practice. METHODS: Radiation oncology centres across Canada
      were contacted to identify radiation oncologists who treat patients with lacc.
      The focus of the survey was patients treated with radical chemoradiotherapy with
      curative intent. An anonymous online tool was used to distribute a 23-item
      questionnaire asking about access to pet imaging, opinions on indications for pet
      imaging, and practice patterns relating to the use of pet in this patient
      population. Questionnaire responses were tabulated and analyzed. RESULTS: The
      response rate was 65% (35 of 54 questionnaire recipients). Most respondents (80%)
      have access to pet for lacc patients, usually restricted to study protocols. Of
      the respondents,48% considered that access to pet was timely. Frequency of
      routine orders for pet before and after treatment (to assess response) was 63%
      and 15% respectively. With better access, 91% of respondents would routinely
      order pet before treatment, and 61% would routinely order it for posttreatment
      assessment. For initial staging, 85% of respondents considered pet to be a
      standard of care, and nearly half (45%) believed it should be a standard of care
      to assess treatment response. Because of access limitations, nearly 70% of
      respondents (23 of 34) do not order pet as often as they feel it is clinically
      indicated, and 74% agree that better access to pet would lead to improved care
      for lacc patients in Canada. CONCLUSIONS: Canadian radiation oncologists support
      the routine use of pet imaging in the initial workup of patients with lacc.
      Access to pet imaging limits routine use for these patients in clinically
      indicated situations. There is strong support for developing guidelines for pet
      use in this patient population.

PMID- 24311950
TI  - Making lifestyle changes after colorectal cancer: insights for program
      development.
AB  - BACKGROUND: Healthy lifestyle behaviours may improve outcomes for people with
      colorectal cancer (crc), but the intention to take action and to change those
      behaviours may vary with time and resource availability. We aimed to estimate the
      prevalence of current lifestyle behaviours in people with and without crc in our
      community, and to identify their desire to change and their resource preferences.
      METHODS: A mixed-methods survey was completed by people diagnosed with crc who
      were pre-treatment (n = 54), undergoing treatment (n = 62), or done with
      treatment for less than 6 months (n = 67) or for more than 6 months (n = 178),
      and by people without cancer (n = 83). RESULTS: Current lifestyle behaviours were
      similar in all groups, with the exception of vigorous physical activity levels,
      which were significantly lower in the pre-treatment and ongoing treatment
      respondents than in cancer-free respondents. Significantly more crc respondents
      than respondents without cancer had made lifestyle changes. Among the crc
      respondents, dietary change was the change most frequently made (39.3%), and
      increased physical activity was the change most frequently desired (39.1%).
      Respondents wanted to use complementary and alternative medicine (cam), reading
      materials, self-efficacy, and group activities to make future changes.
      CONCLUSIONS: Resources for lifestyle change should be made available for people
      diagnosed with crc, and should be tailored to address physical activity, cam, and
      diet. Lifestyle programs offered throughout the cancer trajectory and beyond
      treatment completion might be well received by people with crc.

PMID- 24311951
TI  - Cross-disciplinary research in cancer: an opportunity to narrow the knowledge
      practice gap.
AB  - Health services researchers have consistently identified a gap between what is
      identified as "best practice" and what actually happens in clinical care. Despite
      nearly two decades of a growing evidence-based practice movement, narrowing the
      knowledge-practice gap continues to be a slow, complex, and poorly understood
      process. Here, we contend that cross-disciplinary research is increasingly
      relevant and important to reducing that gap, particularly research that
      encompasses the notion of transdisciplinarity, wherein multiple academic
      disciplines and non-academic individuals and groups are integrated into the
      research process. The assimilation of diverse perspectives, research approaches,
      and types of knowledge is potentially effective in helping research teams tackle
      real-world patient care issues, create more practice-based evidence, and
      translate the results to clinical and community care settings. The goals of this
      paper are to present and discuss cross-disciplinary approaches to health research
      and to provide two examples of how engaging in such research may optimize the use
      of research in cancer care. 

PMID- 24311952
TI  - Direct cost for initial management of prostate cancer: a systematic review.
AB  - BACKGROUND: Prostate cancer (pca) is the most common non-skin cancer among men in
      Canada and other Western countries. Increased prevalence and higher cost of newer
      treatments have led to a significant rise in the economic burden of pca. The
      objectives of the present study were to systematically review the literature on
      direct costs for the initial management of pca, and to examine the methodologic
      considerations across studies. METHODS: Bibliographic databases were
      systematically searched for peer-reviewed articles in English. Studies were
      reviewed for methodologic considerations and mean direct cost of active
      surveillance or watchful waiting (as/ww) and initial treatments. Direct cost was
      standardized to 2011 Canadian dollars. RESULTS: After a review of abstracts and
      full-text papers, seventeen articles met the eligibility criteria and were
      included in the review. Studies were published during 1992-2010. The studies
      reported on health care systems in the United States, France, the United Kingdom,
      German, Italy, and Spain. Our review identified a lack of methodologic consensus,
      leading to variation in direct costs between studies. Nevertheless, results
      indicate a significant direct cost of pca treatments. CONCLUSIONS: The existing
      literature lacks methodologically rigorous studies on the direct costs of pca
      treatments specific to publicly funded health care systems. Additional studies
      are required to appreciate the direct costs of newer treatments and the impact of
      their adoption on the growing economic burden of pca management.

PMID- 24311953
TI  - Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients
      undergoing cancer therapy: an observational cohort study.
AB  - BACKGROUND: Patients with cancer are often treated with glucocorticoids (gcs) as
      part of therapy, which may cause hyperglycemia. We sought to define the
      prevalence of, and risk factors for, hyperglycemia in this setting. METHODS:
      Adult patients taking gc as part of therapy protocols for primary brain tumour or
      metastasis, for lymphoma, or for bone marrow transplant (bmt) were screened with
      random glucometer measurements taken at least 3 hours after the last dose gcs.
      RESULTS: We screened 90 patients [44.4% women, 55.6% men; mean age: 59.6 years
      (range: 25-82 years); mean body mass index (bmi): 26.4 kg/m(2) (range: 15.8-45.3
      kg/m(2))] receiving gc as part of cancer treatment. Mean total daily gc dose in
      the group was 238.5 mg (range: 30-1067 mg) hydrocortisone equivalents.
      Hyperglycemia (glucose >= 8.0 mmol/L) was found in 58.9% (53 of 90), and diabetes
      mellitus (dm)-range hyperglycemia (glucose >= 11.1 mmol/L) in 18.9% (17 of 90).
      The mean time from gc ingestion to glucometer testing was 5.5 hours (range: 3-20
      hours). Presence of hyperglycemia did not correlate with traditional dm risk
      factors such as age, sex, bmi, and personal or family history of dm. A longer
      interval from gc dose to testing (p < 0.05), a higher gc dose (p = 0.04), and a
      shorter interval between the preceding meal and testing (p = 0.02) were risk
      factors for hyperglycemia in some patient groups. CONCLUSIONS: Glucocorticoid
      induced hyperglycemia is common in patients undergoing cancer treatment and
      cannot be predicted by traditional risk factors for dm. We recommend that all
      cancer patients receiving gc be screened for hyperglycemia at least 4-6 hours
      after gc administration.

PMID- 24311954
TI  - Outcomes of her2-positive early-stage breast cancer in the trastuzumab era: a
      population-based study of Canadian patients.
AB  - Breast cancer is heterogenous, with variable expression of the estrogen receptor
      (er), progesterone receptor (pr), and human epidermal growth factor receptor 2
      (her2). Overexpression of her2 is generally considered a negative prognostic
      feature, but whether outcomes for her2-positive early breast cancer remain
      different from those for other subtypes in the era of trastuzumab-based adjuvant
      therapy is unknown. METHODS: Using a retrospective chart review, we compared
      overall survival (os) and relapse-free survival (rfs) in 3 groups of patients
      with early-stage breast cancer: er-positive or pr-positive (or both) and her2
      negative ["hormone receptor-positive" (hr+)]; her2-positive (her2+); and er
      negative, pr-negative, and her2-negative ["triple-negative" (tn)]. RESULTS: In
      the 503 charts analyzed (332 hr+, 94 her2+, 77 tn), the 5-year os and rfs were,
      respectively, 94.2% and 87.2% for hr+ patients, 88.6% and 74.9% for her2+
      patients, and 85.4% and 76.2% for tn patients. On multivariate analysis, the os
      for the her2+ subtype was similar to that for the hr+ subtype (hazard ratio:1.07;
      95% confidence interval: 0.31 to 3.67 with hr+ as reference), but os was
      significantly worse for tn patients than for hr+ patients (hazard ratio: 4.37;
      95% confidence interval: 1.56 to 12.24). In her2+ patients, the 5-year os and rfs
      trended better for patients with er+ or pr+ disease than for patients with er
      negative and pr-negative disease (5-year os: 92.1% vs. 86.9%; 5-year rfs: 79.8%
      vs. 71.4%). Of her2+ patients, just 80.9% received trastuzumab, including 33.3%
      of her2+ patients with sub-centimetre tumours. CONCLUSIONS: In the trastuzumab
      era, patients with her2+ and hr+ early breast cancer have similar outcomes, while
      tn patients experience a significantly worse os than either of the foregoing
      groups. Outcomes for her2+ patients may differ by er and pr status. Trastuzumab
      was underutilized in this cohort.

PMID- 24311955
TI  - Prognostic factors associated with the response to sunitinib in patients with
      metastatic renal cell carcinoma.
AB  - OBJECTIVE: We investigated the prognostic clinicopathologic factors associated
      with overall survival (os) and progression-free survival (pfs) in the once-daily
      continuous administration of first-line sunitinib in a consecutive cohort of
      Turkish patients with metastatic renal cell carcinoma (rcc). METHODS: The study
      enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a
      continuous once-daily dosing regimen between April 2006 and April 2011.
      Univariate analyses were performed using the log-rank test. RESULTS: Median
      follow-up was 18.5 months. In univariate analyses, poor pfs and os were
      associated with 4 of the 5 factors in the Memorial Sloan-Kettering Cancer Center
      (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or
      higher, low hemoglobin, high corrected serum calcium, and high lactate
      dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2
      metastatic sites, liver metastasis, non-clear cell histology, and the presence of
      sarcomatoid features on pathology were also associated with poor pfs; and male
      sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung
      metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of
      sarcomatoid features were also associated with poorer os. The application of the
      mskcc model distinctly separated the pfs and os curves (p < 0.001). CONCLUSIONS:
      Our study identified prognostic factors for pfs and os with the use sunitinib as
      first-line metastatic rcc therapy and confirmed that the mskcc model still
      appears to be valid for predicting survival in metastatic rcc in the era of
      molecular targeted therapy.

PMID- 24311956
TI  - The association between malnutrition and psychological distress in patients with
      advanced head-and-neck cancer.
AB  - OBJECTIVE: Malnutrition and psychological distress are often seen in patients
      with head-and-neck cancer, but little is known about the interrelationships
      between those two symptoms. The present study examined the relationship between
      malnutrition and psychological distress in patients with advanced head-and-neck
      cancer. METHODS: Using the Patient-Generated Subjective Global Assessment, 99
      patients with advanced-stage head-and-neck cancer were screened for nutrition
      status. The patients were also screened for psychosocial distress (using the
      Distress Thermometer) and for psychosocial issues (using the Problem Checklist).
      Any relationship between malnutrition and psychosocial distress was determined by
      regression and correlation analysis. We also used t-tests to compare distress
      levels for patients with and without specific nutrition-related symptoms.
      RESULTS: The study group included 80 men and 19 women [mean age: 58.4 +/- 10.9
      years (range: 23-85 years)]. The correlation between poorer nutrition status and
      level of psychological distress was significant r = 0.37 (p < 0.001).
      Specifically, reduced food intake and symptoms were both positively associated
      with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01.
      After controlling for the effects of psychosocial problems and pain, nutrition
      status remained a significant predictor of distress, explaining 3.8% of the
      variance in the distress scores of the patients (p < 0.05). CONCLUSIONS:
      Malnutrition and symptoms were strongly related to distress in patients with
      advanced head-and-neck cancer. Our results suggest the need for further research
      into the complex relationship between nutrition status and distress and into the
      management of both nutrition and distress in cancer care.

PMID- 24311957
TI  - Meeting the health information needs of prostate cancer patients using personal
      health records.
AB  - BACKGROUND: There is interest in the use of health information technology in the
      form of personal health record (phr) systems to support patient needs for health
      information, care, and decision-making, particularly for patients with
      distressing, chronic diseases such as prostate cancer (pca). We sought feedback
      from pca patients who used a phr. METHODS: For 6 months, 22 pca patients in
      various phases of care at the BC Cancer Agency (bcca) were given access to a
      secure Web-based phr called provider, which they could use to view their medical
      records and use a set of support tools. Feedback was obtained using an end-of
      study survey on usability, satisfaction, and concerns with provider. Site
      activity was recorded to assess usage patterns. RESULTS: Of the 17 patients who
      completed the study, 29% encountered some minor difficulties using provider. No
      security breaches were known to have occurred. The two most commonly accessed
      medical records were laboratory test results and transcribed doctor's notes. Of
      survey respondents, 94% were satisfied with the access to their medical records,
      65% said that provider helped to answer their questions, 77% felt that their
      privacy and confidentiality were preserved, 65% felt that using provider helped
      them to communicate better with their physicians, 83% found new and useful
      information that they would not have received by talking to their health care
      providers, and 88% said that they would continue to use provider. CONCLUSIONS:
      Our results support the notion that phrs can provide cancer patients with timely
      access to their medical records and health information, and can assist in
      communication with health care providers, in knowledge generation, and in patient
      empowerment.

PMID- 24311958
TI  - Sensitivity and specificity of the Distress Thermometer in screening for distress
      in long-term nasopharyngeal cancer survivors.
AB  - BACKGROUND: The Distress Thermometer (dt) is a screening tool recommended to
      quickly identify cancer patients with distress. Our study aimed to examine the
      sensitivity and specificity of the dt in detecting psychological distress in long
      term Chinese nasopharyngeal cancer (npc) survivors. METHODS: Data for the 442
      participating npc survivors were collected through a self-administered
      questionnaire based on the dt and the Hospital Anxiety and Depression Scale
      (hads). The hads was used to define cases of psychological distress. Positive and
      negative groups were defined based on 4 hads criteria (Anxiety, Depression,
      Anxiety or Depression, and overall score). Receiver operating characteristic
      (roc) curves were used to examine the ability of all possible cut-off values of
      the dt to detect positive and negative cases. For each roc curve, the area under
      the curve (auc) was used as an indicator of the overall accuracy of the dt to
      identify positive cases of distress. RESULTS: The positive auc values [with 95%
      confidence intervals (ci)] for the 4 hads criteria were 0.715 (95% ci: 0.667 to
      0.764), 0.714 (95% ci: 0.661 to 0.768), 0.724 (95% ci: 0.677 to 0.771), and 0.724
      (95% ci: 0.664 to 0.775) respectively. At a cut-off score of 4, the sensitivity
      of the dt to the four hads criteria was, respectively, 0.366 (95% ci: 0.296 to
      0.436), 0.448 (95% ci: 0.364 to 0.532), 0.362 (95% ci: 0.299 to 0.425), and 0.421
      (95% ci: 0.339 to 0.502), and the specificity of the dt to the 4 hads criteria
      was, respectively, 0.860 (95% ci: 0.818 to 0.902), 0.860 (95% ci: 0.821 to
      0.899), 0.854 (95% ci: 0.814 to 0.894), and 0.854 (95% ci: 0.814 to 0.894). At a
      cut-off score of 5, the corresponding sensitivities were lower than those at the
      cut-off score of 4. All potential cut-off scores showed poor sensitivity (<0.90).
      CONCLUSIONS: The roc analysis showed poor discrimination. No potential dt cut-off
      score had an acceptable sensitivity. The dt showed poor sensitivity in npc
      survivors. Thus, the dt might not be a valid scale for psychological distress
      screening in long-term Chinese npc survivors.

PMID- 24311959
TI  - Superficial parotid lobe-sparing delineation approach: a better method of dose
      optimization to protect the parotid gland in intensity-modulated radiotherapy for
      nasopharyngeal carcinoma.
AB  - PURPOSE: We used a superficial parotid lobe-sparing delineation approach for dose
      optimization with better protection for the parotid glands in intensity-modulated
      radiotherapy (imrt) for nasopharyngeal carcinoma (npc) patients. METHODS:
      Compared with traditional contouring of the entire parotid glands as organs at
      risk (oars) in imrt for npc, we used a superficial parotid lobe-sparing
      delineation approach of contouring the superficial parotid lobes as oars. Changes
      in dose to the parotid glands, the targets, and other oars were evaluated.
      RESULTS: The mean dose to the parotid glands overall decreased by more than 4 Gy
      in the test plans. Impressively, the mean dose to the superficial parotid lobes
      in the test plans was not more than 30 Gy, regardless of clinical stage. In T1-3
      npc patients, the dose distributions for targets were not significantly different
      in the control plans and the test plans. However, for some T4 patients, the dose
      distributions for targets and brainstem in the test plans could not meet clinical
      requirements. CONCLUSIONS: The superficial parotid lobe-sparing delineation
      approach can significantly lower the mean dose to the entire parotid and to the
      superficial parotid lobe in T1-3 npc patients, which would be expected to result
      in less xerostomia and better quality of life for those patients.

PMID- 24311960
TI  - Irradiation after surgery for breast cancer patients with primary tumours and one
      to three positive axillary lymph nodes: yes or no?
AB  - OBJECTIVE AND METHODS: We retrospectively analyzed clinicopathologic features and
      survival in breast cancer patients who had T1 or T2 primary tumours and 1-3
      histologically involved axillary lymph nodes and who were treated with modified
      radical mastectomy without adjuvant radiotherapy (rt). We also explored prognosis
      to find the high- and low-risk groups. RESULTS: From May 2001 to April 2005, 368
      patients treated at Tianjin Tumor Hospital met the study criteria. The 5- and 8
      year rates were 7.2% and 10.7% for locoregional recurrence (lrr), 85.1% and 77.7%
      for disease-free survival (dfs), and 92.8% and 89.3% for overall survival (os).
      Multivariate Cox regression analysis showed that age, tumour size, estrogen
      receptor (er) status, and lymphovascular invasion (lvi) were independent
      prognostic factors for lrr and dfs. Based on 4 patient-related factors that
      indicate poor prognosis (age < 40 years, tumour > 3 cm, er negativity, and lvi),
      the high-risk group (patients with 3 or 4 factors, accounting for 12.5% of the
      cohort) had 5- and 8-year rates of 24.3% and 36.9% for lrr, 57.2% and 39.2% for
      dfs, and 74.8% and 43.8% for os compared with 5.0% and 7.1% for lrr, 88.9% and
      83.1% for dfs, 91.6% and 83.4% for os in the low-risk group (patients with 0-2
      factors, accounting for 87.5% of the cohort; p < 0.001). CONCLUSIONS: Our study
      identified several risk factors that correlated independently with a greater
      incidence of lrr and distant metastasis in patients with T1 and T2 breast cancer
      and 1-3 positive nodes. Patients with 0-2 risk factors may not be likely to
      benefit from post-mastectomy rt, but patients with 3-4 risk factors may need rt
      to optimize locoregional control and improve survival.

PMID- 24311961
TI  - Comparison of recurrence and survival rates after breast-conserving therapy and
      mastectomy in young women with breast cancer.
AB  - Multiple randomized trials have demonstrated that breast-conserving therapy with
      partial mastectomy and radiotherapy provides survival equivalent to that seen
      with mastectomy for patients with early-stage breast cancer. Breast-conserving
      therapy has been associated with better quality of life relative to mastectomy
      and has become the standard of care for patients with early-stage breast cancer.
      Young age has been identified as a risk factor for recurrence and death from
      breast cancer. Some studies have suggested that young women (less than 35 or 40
      years of age) have inferior outcomes with breast-conserving therapy, implying
      that such women may be better served by mastectomy. On review of the available
      literature, there is no definitive evidence that mastectomy provides a
      consistent, unequivocal recurrence-free or overall survival benefit over breast
      conserving therapy. However, available meta-analyses have not compared outcomes
      in young women specifically, and such analyses should be performed. In the
      interim, breast-conserving therapy is not contraindicated in young women (less
      than 40 years of age) and can be used cautiously; however, such women should be
      advised of the lack of unequivocal data proving that survival is equivalent to
      that with mastectomy in their age group. 

PMID- 24311963
TI  - Metaphors and malignancy: making sense of cancer.

PMID- 24311962
TI  - Oncofertility in Canada: gonadal protection and fertility-sparing strategies.
AB  - BACKGROUND: Cancer can be a devastating diagnosis. In particular, malignancy and
      its indicated treatments have profoundly negative effects on the fertility of
      young cancer patients. Oncofertility has emerged as a new interdisciplinary field
      to address the issue of gonadotoxicity associated with cancer therapies and to
      facilitate fertility preservation. In Canada, fertility issues are often
      inadequately addressed despite the availability of resources. The goal of this
      four-part series is to facilitate systemic improvements in fertility preservation
      for adolescent and young adult Canadians with a new diagnosis of cancer. METHODS:
      Here, we review the fertility preservation measures currently available. Medical
      and surgical strategies are both outlined. RESULTS: Fertility-preserving
      strategies and gonadal protection have demonstrated variable success in a number
      of approaches. The value of hormone suppression is still in question for women.
      Progestins for endometrial cancer and alternative chemotherapies are other
      medical approaches. Gonadal shielding and protective surgical approaches have
      also been attempted. CONCLUSIONS: The techniques discussed here may be
      selectively considered and integrated into patient care in an attempt to preserve
      future fertility before initiating cancer treatment.

PMID- 24311964
TI  - Adenocarcinoma not otherwise specified or cribriform adenocarcinoma on dorsum of
      tongue?

PMID- 24311965
TI  - Weakly hormone receptor-positive breast cancer and use of adjuvant hormonal
      therapy.

PMID- 24311966
TI  - Response to "Adenocarcinoma not otherwise specified or cribriform adenocarcinoma
      on dorsum of tongue?".

PMID- 24311967
TI  - Microarrayed Materials for Stem Cells.
AB  - Stem cells hold remarkable promise for applications in disease modeling, cancer
      therapy and regenerative medicine. Despite the significant progress made during
      the last decade, designing materials to control stem cell fate remains
      challenging. As an alternative, materials microarray technology has received
      great attention because it allows for high throughput materials synthesis and
      screening at a reasonable cost. Here, we discuss recent developments in materials
      microarray technology and their applications in stem cell engineering. Future
      opportunities in the field will also be reviewed.

PMID- 24311968
TI  - Development of rapid methodologies for the isolation and quantitation of drug
      metabolites by differential mobility spectrometry - mass spectrometry.
AB  - Clinical and forensic toxicology laboratories are inundated with thousands of
      samples requiring lengthy chromatographic separations prior to mass spectrometry.
      Here, we employ differential mobility spectrometry (DMS) interfaced to nano
      electrospray ionization-mass spectrometry to provide a rapid ion filtration
      technique for the separation of ions in gas phase media prior to mass spectral
      analysis on a DMS-integrated AB SCIEX API 3000 triple-quadrupole mass
      spectrometer. DMS is efficient at the rapid separation of ions under ambient
      conditions and provides many advantages when used as an ion filtration technique
      in tandem with mass spectrometry (MS) and MS/MS. Our studies evaluated DMS-MS/MS
      as a rapid, quantitative platform for the analysis of drug metabolites isolated
      from urine samples. In targeted applications, five metabolites of common drugs of
      abuse were effectively and rapidly separated using isopropanol and ethyl acetate
      as transport gas modifiers, eliminating the gas chromatography or liquid
      chromatography-based separations commonly employed in clinical and forensic
      toxicology laboratories. Calibration curves were prepared for the selected drug
      metabolites utilizing deuterated internal standards for quantitative purposes.
      The feasibility of separating and quantitating drug metabolites in a rapid
      fashion was evaluated by compensation voltage stepping followed by multiple
      reaction monitoring (MRM) detection. Rapid profiling of clinical and forensic
      toxicology samples could help to address an urgent need within the scientific
      community by developing high-throughput analytical methodologies, which could
      reduce significant case backlogs present within these laboratories.

PMID- 24311969
TI  - Rigid microenvironments promote cardiac differentiation of mouse and human
      embryonic stem cells.
AB  - While adult heart muscle is the least regenerative of tissues, embryonic
      cardiomyocytes are proliferative, with embryonic stem (ES) cells providing an
      endless reservoir. In addition to secreted factors and cell-cell interactions,
      the extracellular microenvironment has been shown to play an important role in
      stem cell lineage specification, and understanding how scaffold elasticity
      influences cardiac differentiation is crucial to cardiac tissue engineering.
      Though previous studies have analyzed the role of the matrix elasticity on the
      function of differentiated cardiomyocytes, whether it affects the induction of
      cardiomyocytes from pluripotent stem cells is poorly understood. Here, we
      examined the role of matrix rigidity on the cardiac differentiation using mouse
      and human ES cells. Culture on polydimethylsiloxane (PDMS) substrates of varied
      monomer-to-crosslinker ratios revealed that rigid extracellular matrices promote
      a higher yield of de novo cardiomyocytes from undifferentiated ES cells. Using an
      genetically modified ES system that allows us to purify differentiated
      cardiomyocytes by drug selection, we demonstrate that rigid environments induce
      higher cardiac troponin T expression, beating rate of foci, and expression ratio
      of adult alpha- to fetal beta- myosin heavy chain in a purified cardiac
      population. M-mode and mechanical interferometry image analyses demonstrate that
      these ES-derived cardiomyocytes display functional maturity and synchronization
      of beating when co-cultured with neonatal cardiomyocytes harvested from a
      developing embryo. Together, these data identify matrix stiffness as an
      independent factor that instructs not only the maturation of the already
      differentiated cardiomyocytes but also the induction and proliferation of
      cardiomyocytes from undifferentiated progenitors. Manipulation of the stiffness
      will help direct the production of functional cardiomyocytes en masse from stem
      cells for regenerative medicine purposes.

PMID- 24311970
TI  - Infant Brain Responses to Object Weight: Exploring Goal-Directed Actions and Self
      Experience.
AB  - Recent work has suggested the value of electroencephalographic (EEG) measures in
      the study of infants' processing of human action. Studies in this area have
      investigated desynchronization of the sensorimotor mu rhythm during action
      execution and action observation in infancy. Untested but critical to theory is
      whether the mu rhythm shows a differential response to actions which share
      similar goals but have different motor requirements or sensory outcomes. By
      varying the invisible property of object weight, we controlled for the abstract
      goal (reach, grasp, and lift the object), while allowing other aspects of the
      action to vary. The mu response during 14-month-old infants' own executed actions
      showed a differential hemispheric response between acting on heavier and lighter
      objects. EEG responses also showed sensitivity to "expected object weight" when
      infants simply observed an experimenter reach for objects that the infants' prior
      experience indicated were heavier versus lighter. Crucially, this neural
      reactivity was predictive - during the observation of the other reaching toward
      the object, before lifting occurred. This suggests that infants' own self
      experience with a particular object's weight influences their processing of
      others' actions on the object, with implications for developmental social
      cognitive neuroscience.

PMID- 24311971
TI  - Adapting Semantic Natural Language Processing Technology to Address Information
      Overload in Influenza Epidemic Management.
AB  - Explosion of disaster health information results in information overload among
      response professionals. The objective of this project was to determine the
      feasibility of applying semantic natural language processing (NLP) technology to
      addressing this overload. The project characterizes concepts and relationships
      commonly used in disaster health-related documents on influenza pandemics, as the
      basis for adapting an existing semantic summarizer to the domain. Methods include
      human review and semantic NLP analysis of a set of relevant documents. This is
      followed by a pilot-test in which two information specialists use the adapted
      application for a realistic information seeking task. According to the results,
      the ontology of influenza epidemics management can be described via a manageable
      number of semantic relationships that involve concepts from a limited number of
      semantic types. Test users demonstrate several ways to engage with the
      application to obtain useful information. This suggests that existing semantic
      NLP algorithms can be adapted to support information summarization and
      visualization in influenza epidemics and other disaster health areas. However,
      additional research is needed in the areas of terminology development (as many
      relevant relationships and terms are not part of existing standardized
      vocabularies), NLP, and user interface design.

PMID- 24311972
TI  - Region duplication forgery detection technique based on SURF and HAC.
AB  - Region duplication forgery detection is a special type of forgery detection
      approach and widely used research topic under digital image forensics. In copy
      move forgery, a specific area is copied and then pasted into any other region of
      the image. Due to the availability of sophisticated image processing tools, it
      becomes very hard to detect forgery with naked eyes. From the forged region of an
      image no visual clues are often detected. For making the tampering more robust,
      various transformations like scaling, rotation, illumination changes, JPEG
      compression, noise addition, gamma correction, and blurring are applied. So there
      is a need for a method which performs efficiently in the presence of all such
      attacks. This paper presents a detection method based on speeded up robust
      features (SURF) and hierarchical agglomerative clustering (HAC). SURF detects the
      keypoints and their corresponding features. From these sets of keypoints,
      grouping is performed on the matched keypoints by HAC that shows copied and
      pasted regions. 

PMID- 24311973
TI  - Recent achievement in gene cloning and functional genomics in soybean.
AB  - Soybean is a model plant for photoperiodism as well as for symbiotic nitrogen
      fixation. However, a rather low efficiency in soybean transformation hampers
      functional analysis of genes isolated from soybean. In comparison, rapid
      development and progress in flowering time and photoperiodic response have been
      achieved in Arabidopsis and rice. As the soybean genomic information has been
      released since 2008, gene cloning and functional genomic studies have been
      revived as indicated by successfully characterizing genes involved in maturity
      and nematode resistance. Here, we review some major achievements in the cloning
      of some important genes and some specific features at genetic or genomic levels
      revealed by the analysis of functional genomics of soybean. 

PMID- 24311974
TI  - Evaluation of genotoxic effects of new molecules with possible trypanocidal
      activity for Chagas disease treatment.
AB  - Chagas disease is responsible for a large number of human infections and many are
      also at risk of infection. There is no effective drug for Chagas disease
      treatment. The Institute of Pharmaceutical Technology at Fiocruz, Brazil, has
      designed three nitro analogs of the nitroimidazole-thiadiazole, megazol: two
      triazole analogs PTAL 05-02 and PAMT 09 and a pyrazole analog PTAL 04-09. A set
      of Salmonella enterica serovar Typhimurium strains were used in the bacterial
      reverse mutation test (Ames test) to determine the mutagenicity and cytotoxicity
      of megazol and its nitro analogs. Megazol presented positive mutagenic activity
      at very low concentration, either with or without metabolic activation S9 mix.
      The mutagenic response of the analogs was detected at higher concentration than
      the lowest megazol concentration to yield mutagenic activity showing that new
      advances can be made to develop new analogs. The micronucleus test with rat
      macrophage cells was used in the genotoxic evaluation. The analogs were capable
      of inducing micronucleus formation and showed cytotoxic effects. PTAL 04-09
      structural modifications might be better suitable for the design of promising new
      drugs candidate for Chagas' disease treatment. 

PMID- 24311975
TI  - Anthropometry and body composition status during Ramadan among higher institution
      learning centre staffs with different body weight status.
AB  - This study was done to observe the anthropometry and body composition changes
      before, during, and after the holy month of Ramadan. This study was carried out
      on 46 staff from one of the local universities, which comprised of 14 males and
      32 females ranging in age from 25 to 40 years old. There were four sessions done
      to complete this study, namely, a week before Ramadan (T1), 1st week of Ramadan
      (T2), 3rd week of Ramadan (T3), and a month after Ramadan (T4). All subjects were
      assessed according to weight, body circumference, and body composition status. It
      was found that subjects with different weight status showed a significant
      reduction in weight (P < 0.01) but no significant reduction in body fat
      percentage (P < 0.05). The findings suggest that weight reduction does not
      promise a reduction in body fat. Changes in neck circumference were only found in
      normal subjects. Hence, it can be said that overweight and obese subjects showed
      no changes in anthropometry status during Ramadan. No changes in body composition
      were reported in all three weight groups except for trunk body fat. In
      conclusion, normal subjects showed significant changes in various anthropometry
      parameters, but overweight and obese subjects showed no obvious difference. 

PMID- 24311976
TI  - Applying outdoor environment to develop health, comfort, and energy saving in the
      office in hot-humid climate.
AB  - A human life demand set to emerge in the future is the achievement of
      sustainability by maintaining a comfortable indoor environment without excessive
      reliance on energy-consuming air conditioners. The major research processes in
      this study are: (1) measuring indoor air quality and thermal comfort to evaluate
      the comfort of an indoor environment; (2) implementing questionnaire survey
      analysis to explore people's environmental self-perceptions and conducting a meta
      analysis of the measurement results for air quality and physical aspects; and (3)
      constructing an indoor monitoring and management system. The experimental and
      analysis results of this research reveal that most of the office occupants
      preferred a cooler environment with a lower temperature. Additionally, because
      the summers in Taiwan are humid and hot, the occupants of an indoor space tend to
      feel uncomfortable because of the high humidity and poor indoor air quality.
      Therefore, Variable Air Volume (VAV), two air intakes, and exhaust plant are
      installed to improve indoor environment. After improvement, a lower temperature
      (approximately 21.2-23.9 degrees C) indirectly reduces humidity, thereby making
      the occupants comfortable. Increasing air velocity to 0.1~0.15 m/s, the carbon
      dioxide concentrations decrease below the requirement of the WHO. Ninety-five
      percent of the workers corresponded to the standard comfort zone after this
      improvement.

PMID- 24311977
TI  - Ductility enhancement of post-Northridge connections by multilongitudinal voids
      in the beam web.
AB  - Since the earthquakes in Northridge and Kobe in 1994 and 1995, respectively, many
      investigations have been carried out towards improving the strength and ductility
      of steel beam to column pre- and post-Northridge connections. In order to achieve
      these objectives, recent researches are mainly focused on three principles:
      reducing the beam section to improve the beam ductility, adding different kinds
      of slit damper to beam and column flanges to absorb and dissipate the input
      earthquake energy in the connection and strengthening the connection area using
      additional elements such as rib plates, cover plates, and flange plates to keep
      the plastic hinges away from the column face. This paper presents a reduced beam
      section approach via the introduction of multilongitudinal voids (MLV) in the
      beam web for various beam depths varying from 450 mm to 912 mm. ANSYS finite
      element program was used to simulate the three different sizes of SAC sections:
      SAC3, SAC5, and SAC7. Results showed an improvement in the connection ductility
      since the input energy was dissipated uniformly along the beam length and the
      total rotation of the connection was over four percent radian. 

PMID- 24311978
TI  - Smoking prevalence increases following Canterbury earthquakes.
AB  - BACKGROUND: A magnitude 7.1 earthquake hit Canterbury in September 2010. This
      earthquake and associated aftershocks took the lives of 185 people and
      drastically changed residents' living, working, and social conditions. AIM: To
      explore the impact of the earthquakes on smoking status and levels of tobacco
      consumption in the residents of Christchurch. METHODS: Semistructured interviews
      were carried out in two city malls and the central bus exchange 15 months after
      the first earthquake. A total of 1001 people were interviewed. RESULTS: In August
      2010, prior to any earthquake, 409 (41%) participants had never smoked, 273 (27%)
      were currently smoking, and 316 (32%) were ex-smokers. Since the September 2010
      earthquake, 76 (24%) of the 316 ex-smokers had smoked at least one cigarette and
      29 (38.2%) had smoked more than 100 cigarettes. Of the 273 participants who were
      current smokers in August 2010, 93 (34.1%) had increased consumption following
      the earthquake, 94 (34.4%) had not changed, and 86 (31.5%) had decreased their
      consumption. 53 (57%) of the 93 people whose consumption increased reported that
      the earthquake and subsequent lifestyle changes as a reason to increase smoking.
      CONCLUSION: 24% of ex-smokers resumed smoking following the earthquake, resulting
      in increased smoking prevalence. Tobacco consumption levels increased in around
      one-third of current smokers.

PMID- 24311979
TI  - A multimethodology contractor assessment model for facilitating green innovation:
      the view of energy and environmental protection.
AB  - The trends of the green supply chain are attributed to pressures from the
      environment and from customers. Green innovation is a practice for creating
      competitive advantage in sustainable development. To keep up with the changing
      business environment, the construction industry needs an appropriate assessment
      tool to examine the intrinsic and extrinsic effects regarding corporate
      competitive advantage. From the viewpoint of energy and environmental protection,
      this study combines four scientific methodologies to develop an assessment model
      for the green innovation of contractors. System dynamics can be used to estimate
      the future trends for the overall industrial structure and is useful in
      predicting competitive advantage in the industry. The analytic hierarchy process
      (AHP) and utility theory focus on the customer's attitude toward risk and are
      useful for comprehending changes in objective requirements in the environment.
      Fuzzy logic can simplify complicated intrinsic and extrinsic factors and express
      them with a number or ratio that is easy to understand. The proposed assessment
      model can be used as a reference to guide the government in examining the public
      constructions that qualified green contractors participate in. Additionally, the
      assessment model serves an indicator of relative competitiveness that can help
      the general contractor and subcontractor to evaluate themselves and further green
      innovations. 

PMID- 24311980
TI  - Micelle-assisted synthesis of Al2O3.CaO nanocatalyst: optical properties and
      their applications in photodegradation of 2,4,6-trinitrophenol.
AB  - Calcium oxide (CaO) nanoparticles are known to exhibit unique property due to
      their high adsorption capacity and good catalytic activity. In this work the CaO
      nanocatalysts were prepared by hydrothermal method using anionic surfactant,
      sodium dodecyl sulphate (SDS), as a templating agent. The as-synthesized
      nanocatalysts were further used as substrate for the synthesis of alumina doped
      calcium oxide (Al2O3.CaO) nanocatalysts via deposition-precipitation method at
      the isoelectric point of CaO. The Al2O3.CaO nanocatalysts were characterized by
      FTIR, XRD, TGA, TEM, and FESEM techniques. The catalytic efficiencies of these
      nanocatalysts were studied for the photodegradation of 2,4,6-trinitrophenol
      (2,4,6-TNP), which is an industrial pollutant, spectrophotometrically. The effect
      of surfactant and temperature on size of nanocatalysts was also studied. The
      smallest particle size and highest percentage of degradation were observed at
      critical micelle concentration of the surfactant. The direct optical band gap of
      the Al2O3.CaO nanocatalyst was found as 3.3 eV.

PMID- 24311981
TI  - Impact and implementation of simulation-based training for safety.
AB  - Patient safety is an issue of imminent concern in the high-risk field of
      medicine, and systematic changes that alter the way medical professionals
      approach patient care are needed. Simulation-based training (SBT) is an exemplary
      solution for addressing the dynamic medical environment of today. Grounded in
      methodologies developed by the aviation industry, SBT exceeds traditional
      didactic and apprenticeship models in terms of speed of learning, amount of
      information retained, and capability for deliberate practice. SBT remains an
      option in many medical schools and continuing medical education curriculums
      (CMEs), though its use in training has been shown to improve clinical practice.
      Future simulation-based anesthesiology training research needs to develop methods
      for measuring both the degree to which training translates into increased
      practitioner competency and the effect of training on safety improvements for
      patients. 

PMID- 24311982
TI  - Design and analysis of a dynamic mobility management scheme for wireless mesh
      network.
AB  - Seamless mobility management of the mesh clients (MCs) in wireless mesh network
      (WMN) has drawn a lot of attention from the research community. A number of
      mobility management schemes such as mesh network with mobility management (MEMO),
      mesh mobility management (M(3)), and wireless mesh mobility management (WMM) have
      been proposed. The common problem with these schemes is that they impose uniform
      criteria on all the MCs for sending route update message irrespective of their
      distinct characteristics. This paper proposes a session-to-mobility ratio (SMR)
      based dynamic mobility management scheme for handling both internet and intranet
      traffic. To reduce the total communication cost, this scheme considers each MC's
      session and mobility characteristics by dynamically determining optimal threshold
      SMR value for each MC. A numerical analysis of the proposed scheme has been
      carried out. Comparison with other schemes shows that the proposed scheme
      outperforms MEMO, M(3), and WMM with respect to total cost. 

PMID- 24311983
TI  - On weak-BCC-algebras.
AB  - We describe weak-BCC-algebras (also called BZ-algebras) in which the condition
      (x*y)*z = (x*z)*y is satisfied only in the case when elements x, y belong to the
      same branch. We also characterize ideals, nilradicals, and nilpotent elements of
      such algebras. 

PMID- 24311984
TI  - A community of one: social cognition and auditory verbal hallucinations.
AB  - Auditory verbal hallucinations have attracted a great deal of scientific
      interest, but despite the fact that they are fundamentally a social experience-in
      essence, a form of hallucinated communication-current theories remain firmly
      rooted in an individualistic account and have largely avoided engagement with
      social cognition. Nevertheless, there is mounting evidence for the role of social
      cognitive and social neurocognitive processes in auditory verbal hallucinations,
      and, consequently, it is proposed that problems with the internalisation of
      social models may be key to the experience. 

PMID- 24311985
TI  - NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the
      ascidian second heart field.
AB  - The heart and head muscles share common developmental origins and genetic
      underpinnings in vertebrates, including humans. Parts of the heart and cranio
      facial musculature derive from common mesodermal progenitors that express NKX2-5,
      ISL1, and TBX1. This ontogenetic kinship is dramatically reflected in the
      DiGeorge/Cardio-Velo-Facial syndrome (DGS/CVFS), where mutations of TBX1 cause
      malformations in the pharyngeal apparatus and cardiac outflow tract. Cardiac
      progenitors of the first heart field (FHF) do not require TBX1 and segregate
      precociously from common progenitors of the second heart field (SHF) and
      pharyngeal muscles. However, the cellular and molecular mechanisms that govern
      heart versus pharyngeal muscle specification within this lineage remain elusive.
      Here, we harness the simplicity of the ascidian larva to show that, following
      asymmetric cell division of common progenitors, NK4/NKX2-5 promotes
      GATAa/GATA4/5/6 expression and cardiac specification in the second heart
      precursors by antagonizing Tbx1/10-mediated inhibition of GATAa and activation of
      Collier/Olf/EBF (COE), the determinant of atrial siphon muscle (ASM)
      specification. Our results uncover essential regulatory connections between the
      conserved cardio-pharyngeal factor Tbx1/10 and muscle determinant COE, as well as
      a mutual antagonism between NK4 and Tbx1/10 activities upstream of GATAa and COE.
      The latter cross-antagonism underlies a fundamental heart versus pharyngeal
      muscle fate choice that occurs in a conserved lineage of cardio-pharyngeal
      progenitors. We propose that this basic ontogenetic motif underlies cardiac and
      pharyngeal muscle development and evolution in chordates. 

PMID- 24311986
TI  - TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and
      favoring cell migration.
AB  - Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently
      overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4
      protein is predominantly found at tight junctions (TJs) in normal mammary
      epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How
      TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4
      possesses a novel phosphoinositide (PIP)-binding domain crucial for its
      recruitment to TJs. Of interest, this property is shared by the other members of
      the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to
      TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses
      revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three
      lipids using basic residues exposed at its surface. Cellular studies indicated
      that TRAF4 acts as a negative regulator of TJ and increases cell migration. These
      functions are dependent from its ability to interact with PIPs. Our results
      suggest that TRAF4 overexpression might contribute to breast cancer progression
      by destabilizing TJs and favoring cell migration. 

PMID- 24311987
TI  - 3-OST-7 regulates BMP-dependent cardiac contraction.
AB  - The 3-O-sulfotransferase (3-OST) family catalyzes rare modifications of
      glycosaminoglycan chains on heparan sulfate proteoglycans, yet their biological
      functions are largely unknown. Knockdown of 3-OST-7 in zebrafish uncouples
      cardiac ventricular contraction from normal calcium cycling and electrophysiology
      by reducing tropomyosin4 (tpm4) expression. Normal 3-OST-7 activity prevents the
      expansion of BMP signaling into ventricular myocytes, and ectopic activation of
      BMP mimics the ventricular noncontraction phenotype seen in 3-OST-7 depleted
      embryos. In 3-OST-7 morphants, ventricular contraction can be rescued by
      overexpression of tropomyosin tpm4 but not by troponin tnnt2, indicating that
      tpm4 serves as a lynchpin for ventricular sarcomere organization downstream of 3
      OST-7. Contraction can be rescued by expression of 3-OST-7 in endocardium, or by
      genetic loss of bmp4. Strikingly, BMP misregulation seen in 3-OST-7 morphants
      also occurs in multiple cardiac noncontraction models, including potassium
      voltage-gated channel gene, kcnh2, affected in Romano-Ward syndrome and long-QT
      syndrome, and cardiac troponin T gene, tnnt2, affected in human cardiomyopathies.
      Together these results reveal 3-OST-7 as a key component of a novel pathway that
      constrains BMP signaling from ventricular myocytes, coordinates sarcomere
      assembly, and promotes cardiac contractile function. 

PMID- 24311988
TI  - Why growing retractions are (mostly) a good sign.

PMID- 24311993
TI  - Self assembly of rectangular shapes on concentration programming and
      probabilistic tile assembly models.
AB  - Efficient tile sets for self assembling rectilinear shapes is of critical
      importance in algorithmic self assembly. A lower bound on the tile complexity of
      any deterministic self assembly system for an n * n square is [Formula: see text]
      (inferred from the Kolmogrov complexity). Deterministic self assembly systems
      with an optimal tile complexity have been designed for squares and related shapes
      in the past. However designing [Formula: see text] unique tiles specific to a
      shape is still an intensive task in the laboratory. On the other hand copies of a
      tile can be made rapidly using PCR (polymerase chain reaction) experiments. This
      led to the study of self assembly on tile concentration programming models. We
      present two major results in this paper on the concentration programming model.
      First we show how to self assemble rectangles with a fixed aspect ratio
      (alpha:beta), with high probability, using Theta(alpha + beta) tiles. This result
      is much stronger than the existing results by Kao et al. (Randomized self
      assembly for approximate shapes, LNCS, vol 5125. Springer, Heidelberg, 2008) and
      Doty (Randomized self-assembly for exact shapes. In: proceedings of the 50th
      annual IEEE symposium on foundations of computer science (FOCS), IEEE, Atlanta.
      pp 85-94, 2009)-which can only self assembly squares and rely on tiles which
      perform binary arithmetic. On the other hand, our result is based on a technique
      called staircase sampling. This technique eliminates the need for sub-tiles which
      perform binary arithmetic, reduces the constant in the asymptotic bound, and
      eliminates the need for approximate frames (Kao et al. Randomized self-assembly
      for approximate shapes, LNCS, vol 5125. Springer, Heidelberg, 2008). Our second
      result applies staircase sampling on the equimolar concentration programming
      model (The tile complexity of linear assemblies. In: proceedings of the 36th
      international colloquium automata, languages and programming: Part I on ICALP
      '09, Springer-Verlag, pp 235-253, 2009), to self assemble rectangles (of fixed
      aspect ratio) with high probability. The tile complexity of our algorithm is
      Theta(log(n)) and is optimal on the probabilistic tile assembly model (PTAM)-n
      being an upper bound on the dimensions of a rectangle.

PMID- 24311990
TI  - Timing and completeness of trial results posted at ClinicalTrials.gov and
      published in journals.
AB  - BACKGROUND: The US Food and Drug Administration Amendments Act requires results
      from clinical trials of Food and Drug Administration-approved drugs to be posted
      at ClinicalTrials.gov within 1 y after trial completion. We compared the timing
      and completeness of results of drug trials posted at ClinicalTrials.gov and
      published in journals. METHODS AND FINDINGS: We searched ClinicalTrials.gov on
      March 27, 2012, for randomized controlled trials of drugs with posted results.
      For a random sample of these trials, we searched PubMed for corresponding
      publications. Data were extracted independently from ClinicalTrials.gov and from
      the published articles for trials with results both posted and published. We
      assessed the time to first public posting or publishing of results and compared
      the completeness of results posted at ClinicalTrials.gov versus published in
      journal articles. Completeness was defined as the reporting of all key elements,
      according to three experts, for the flow of participants, efficacy results,
      adverse events, and serious adverse events (e.g., for adverse events, reporting
      of the number of adverse events per arm, without restriction to statistically
      significant differences between arms for all randomized patients or for those who
      received at least one treatment dose). From the 600 trials with results posted at
      ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding
      published article. For trials with both posted and published results (n = 202),
      the median time between primary completion date and first results publicly posted
      was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time
      between primary completion date and journal publication was 21 mo (first quartile
      = 14, third quartile = 28 mo). Reporting was significantly more complete at
      ClinicalTrials.gov than in the published article for the flow of participants
      (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02),
      adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus
      63%, p<0.001). The main study limitation was that we considered only the
      publication describing the results for the primary outcomes. CONCLUSIONS: Our
      results highlight the need to search ClinicalTrials.gov for both unpublished and
      published trials. Trial results, especially serious adverse events, are more
      completely reported at ClinicalTrials.gov than in the published article.

PMID- 24311994
TI  - How Ontologies are Made: Studying the Hidden Social Dynamics Behind Collaborative
      Ontology Engineering Projects.
AB  - Traditionally, evaluation methods in the field of semantic technologies have
      focused on the end result of ontology engineering efforts, mainly, on evaluating
      ontologies and their corresponding qualities and characteristics. This focus has
      led to the development of a whole arsenal of ontology-evaluation techniques that
      investigate the quality of ontologies as a product. In this paper, we aim to shed
      light on the process of ontology engineering construction by introducing and
      applying a set of measures to analyze hidden social dynamics. We argue that
      especially for ontologies which are constructed collaboratively, understanding
      the social processes that have led to its construction is critical not only in
      understanding but consequently also in evaluating the ontology. With the work
      presented in this paper, we aim to expose the texture of collaborative ontology
      engineering processes that is otherwise left invisible. Using historical change
      log data, we unveil qualitative differences and commonalities between different
      collaborative ontology engineering projects. Explaining and understanding these
      differences will help us to better comprehend the role and importance of social
      factors in collaborative ontology engineering projects. We hope that our analysis
      will spur a new line of evaluation techniques that view ontologies not as the
      static result of deliberations among domain experts, but as a dynamic,
      collaborative and iterative process that needs to be understood, evaluated and
      managed in itself. We believe that advances in this direction would help our
      community to expand the existing arsenal of ontology evaluation techniques
      towards more holistic approaches.

PMID- 24311989
TI  - The effect of dosing regimens on the antimalarial efficacy of dihydroartemisinin
      piperaquine: a pooled analysis of individual patient data.
AB  - BACKGROUND: Dihydroartemisinin-piperaquine (DP) is increasingly recommended for
      antimalarial treatment in many endemic countries; however, concerns have been
      raised over its potential under dosing in young children. We investigated the
      influence of different dosing schedules on DP's clinical efficacy. METHODS AND
      FINDINGS: A systematic search of the literature was conducted to identify all
      studies published between 1960 and February 2013, in which patients were enrolled
      and treated with DP. Principal investigators were approached and invited to share
      individual patient data with the WorldWide Antimalarial Resistance Network
      (WWARN). Data were pooled using a standardised methodology. Univariable and
      multivariable risk factors for parasite recrudescence were identified using a
      Cox's regression model with shared frailty across the study sites. Twenty-four
      published and two unpublished studies (n = 7,072 patients) were included in the
      analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier
      survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI
      96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years
      received a total dose of piperaquine below 48 mg/kg (the lower limit recommended
      by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age
      groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%
      96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of
      piperaquine was found to be a significant predictor for recrudescence, the risk
      increasing by 13% (95% CI 5.0%-21%) for every 5 mg/kg decrease in dose; p =
      0.002. In a multivariable model increasing the target minimum total dose of
      piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would
      halve the risk of treatment failure and cure at least 95% of patients; such an
      increment was not associated with gastrointestinal toxicity in the ten studies in
      which this could be assessed. CONCLUSIONS: DP demonstrates excellent efficacy in
      a wide range of transmission settings; however, treatment failure is associated
      with a lower dose of piperaquine, particularly in young children, suggesting
      potential for further dose optimisation.

PMID- 24311995
TI  - The neurobiology of collective action.
AB  - This essay introduces a neurologically-informed mathematical model of collective
      action (CA) that reveals the role for empathy and distress in motivating costly
      helping behaviors. We report three direct tests of model with a key focus on the
      neuropeptide oxytocin as well as a variety of indirect tests. These studies, from
      our lab and other researchers, show support for the model. Our findings indicate
      that empathic concern, via the brain's release of oxytocin, is a trigger for CA.
      We discuss the implications from this model for our understanding why human
      beings engage in costly CA. 

PMID- 24311997
TI  - Decision making under uncertainty.

PMID- 24311996
TI  - Synaptic interactions between perifornical lateral hypothalamic area, locus
      coeruleus nucleus and the oral pontine reticular nucleus are implicated in the
      stage succession during sleep-wakefulness cycle.
AB  - The perifornical area in the posterior lateral hypothalamus (PeFLH) has been
      implicated in several physiological functions including the sleep-wakefulness
      regulation. The PeFLH area contains several cell types including those expressing
      orexins (Orx; also known as hypocretins), mainly located in the PeF nucleus. The
      aim of the present study was to elucidate the synaptic interactions between Orx
      neurons located in the PeFLH area and different brainstem neurons involved in the
      generation of wakefulness and sleep stages such as the locus coeruleus (LC)
      nucleus (contributing to wakefulness) and the oral pontine reticular nucleus
      (PnO) nucleus (contributing to REM sleep). Anatomical data demonstrated the
      existence of a neuronal network involving the PeFLH area, LC, and the PnO nuclei
      that would control the sleep-wake cycle. Electrophysiological experiments
      indicated that PeFLH area had an excitatory effect on LC neurons. PeFLH
      stimulation increased the firing rate of LC neurons and induced an activation of
      the EEG. The excitatory effect evoked by PeFLH stimulation in LC neurons was
      blocked by the injection of the Orx-1 receptor antagonist SB-334867 into the LC.
      Similar electrical stimulation of the PeFLH area evoked an inhibition of PnO
      neurons by activation of GABAergic receptors because the effect was blocked by
      bicuculline application into the PnO. Our data also revealed that the LC and PnO
      nuclei exerted a feedback control on neuronal activity of PeFLH area. Electrical
      stimulation of LC facilitated firing activity of PeFLH neurons by activation of
      catecholaminergic receptors whereas PnO stimulation inhibited PeFLH neurons by
      activation of GABAergic receptors. In conclusion, Orx neurons of the PeFLH area
      seem to be an important organizer of the wakefulness and sleep stages in order to
      maintain a normal succession of stages during the sleep-wakefulness cycle. 

PMID- 24311998
TI  - Invertebrate behavior-actions or responses?

PMID- 24311999
TI  - Robotic goalie with 3 ms reaction time at 4% CPU load using event-based dynamic
      vision sensor.
AB  - Conventional vision-based robotic systems that must operate quickly require high
      video frame rates and consequently high computational costs. Visual response
      latencies are lower-bound by the frame period, e.g., 20 ms for 50 Hz frame rate.
      This paper shows how an asynchronous neuromorphic dynamic vision sensor (DVS)
      silicon retina is used to build a fast self-calibrating robotic goalie, which
      offers high update rates and low latency at low CPU load. Independent and
      asynchronous per pixel illumination change events from the DVS signify moving
      objects and are used in software to track multiple balls. Motor actions to block
      the most "threatening" ball are based on measured ball positions and velocities.
      The goalie also sees its single-axis goalie arm and calibrates the motor output
      map during idle periods so that it can plan open-loop arm movements to desired
      visual locations. Blocking capability is about 80% for balls shot from 1 m from
      the goal even with the fastest-shots, and approaches 100% accuracy when the ball
      does not beat the limits of the servo motor to move the arm to the necessary
      position in time. Running with standard USB buses under a standard preemptive
      multitasking operating system (Windows), the goalie robot achieves median update
      rates of 550 Hz, with latencies of 2.2 +/- 2 ms from ball movement to motor
      command at a peak CPU load of less than 4%. Practical observations and
      measurements of USB device latency are provided. 

PMID- 24312001
TI  - Uncovering the neurochemistry of reward and aversiveness.

PMID- 24312000
TI  - RISC in PD: the impact of microRNAs in Parkinson's disease cellular and molecular
      pathogenesis.
AB  - Parkinson's disease (PD) is a debilitating neurodegenerative disease
      characterized primarily by the selective death of dopaminergic (DA) neurons in
      the substantia nigra pars compacta of the midbrain. Although several genetic
      forms of PD have been identified, the precise molecular mechanisms underlying DA
      neuron loss in PD remain elusive. In recent years, microRNAs (miRNAs) have been
      recognized as potent post-transcriptional regulators of gene expression with
      fundamental roles in numerous biological processes. Although their role in PD
      pathogenesis is still a very active area of investigation, several seminal
      studies have contributed significantly to our understanding of the roles these
      small non-coding RNAs play in the disease process. Among these are studies which
      have demonstrated specific miRNAs that target and down-regulate the expression of
      PD-related genes as well as those demonstrating a reciprocal relationship in
      which PD-related genes act to regulate miRNA processing machinery. Concurrently,
      a wealth of knowledge has become available regarding the molecular mechanisms
      that unify the underlying etiology of genetic and sporadic PD pathogenesis,
      including dysregulated protein quality control by the ubiquitin-proteasome system
      and autophagy pathway, activation of programmed cell death, mitochondrial damage
      and aberrant DA neurodevelopment and maintenance. Following a discussion of the
      interactions between PD-related genes and miRNAs, this review highlights those
      studies which have elucidated the roles of these pathways in PD pathogenesis. We
      highlight the potential of miRNAs to serve a critical regulatory role in the
      implicated disease pathways, given their capacity to modulate the expression of
      entire families of related genes. Although few studies have directly linked miRNA
      regulation of these pathways to PD, a strong foundation for investigation has
      been laid and this area holds promise to reveal novel therapeutic targets for PD.

PMID- 24312002
TI  - Properties of BK-type Ca(+) (+)-dependent K(+) channel currents in medial
      prefrontal cortex pyramidal neurons in rats of different ages.
AB  - The medial prefrontal cortex (PFC) is involved in cognitive functions, which
      undergo profound changes during adolescence. This alteration of the PFC function
      derives from neuron activity, which, in turn, may depend on age-dependent
      properties and the expression of neuronal ion channels. BK-type channels are
      involved in controlling both the Ca(+) (+) ion concentration in the cell interior
      and cell excitability. The purpose of this study was to test the properties of BK
      currents in the medial PFC pyramidal neurons of young (18- to 22-day-old),
      adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell
      currents evoked by depolarizing voltage steps were recorded from dispersed medial
      PFC pyramidal neurons. A selective BK channel blocker - paxilline (10 MUM) -
      irreversibly decreased the non-inactivating K(+) current in neurons that were
      isolated from the young and adult rats. This current was not significantly
      affected by paxilline in the neurons obtained from adolescent rats. The
      properties of single-channel K(+) currents were recorded from the soma of
      dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the
      K(+) channel currents that were recorded, ~90% were BK and leak channel currents.
      The BK-type channel currents were dependent on the Ca(+) (+) concentration and
      the voltage and were inhibited by paxilline. The biophysical properties of the BK
      channel currents did not differ among the pyramidal neurons isolated from young,
      adolescent, and adult rats. Among all of the recorded K(+) channel currents,
      38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from
      the young, adolescent, and adult rats, respectively. Furthermore, application of
      paxilline effectively prolonged the half-width of the action potential in
      pyramidal neurons in slices isolated from young and adult rats but not in neurons
      isolated from adolescent rats. We conclude that the availability of BK channel
      currents decreases in medial PFC pyramidal neurons of adolescent rats compared
      with those in the neurons of young and adult rats while their properties did not
      change across ages. 

PMID- 24312003
TI  - Recent developments of protein kinase inhibitors as potential AD therapeutics.
AB  - Present Alzheimer's disease (AD) therapies suffer from inefficient effects on AD
      symptoms like memory or cognition, especially in later states of the disease.
      Used acteylcholine esterase inhibitors or the NMDA receptor antagonist memantine
      address one target structure which is involved in a complex, multifactorial
      disease progression. So the benefit for patients is presently poor. A more close
      insight in the AD progression identified more suggested target structures for
      drug development. Strategies of AD drug development concentrate on novel target
      structures combined with the established ones dedicated for combined therapy
      regimes, preferably by the use of one drug which may address two target
      structures. Protein kinases have been identified as promising target structures
      because they are involved in AD progression pathways like pathophysiological tau
      protein phosphorylations and amyloid beta toxicity. The review article will
      shortly view early inhibitors of single protein kinases like glycogen synthase
      kinase (gsk3) beta and cyclin dependent kinase 5. Novel inhibitors will be
      discussed which address novel AD relevant protein kinases like dual-specificity
      tyrosine phosphorylation regulated kinase 1A (DYRK1A). Moreover, multitargeting
      inhibitors will be presented which target several protein kinases and those which
      are suspected in influencing other AD relevant processes. Such a multitargeting
      is the most promising strategy to effectively hamper the multifactorial disease
      progression and thus gives perspective hopes for a future better patient benefit.

PMID- 24312004
TI  - A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the
      nervous system.
AB  - Within the nervous system, intracellular Cl(-) and pH regulate fundamental
      processes including cell proliferation, metabolism, synaptic transmission, and
      network excitability. Cl(-) and pH are often co-regulated, and network activity
      results in the movement of both Cl(-) and H(+). Tools to accurately measure these
      ions are crucial for understanding their role under physiological and
      pathological conditions. Although genetically-encoded Cl(-) and pH sensors have
      been described previously, these either lack ion specificity or are unsuitable
      for neuronal use. Here we present ClopHensorN-a new genetically-encoded
      ratiometric Cl(-) and pH sensor that is optimized for the nervous system. We
      demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify
      Cl(-) and H(+) concentrations under a variety of conditions. In addition, we
      establish the sensor's utility by characterizing activity-dependent ion dynamics
      in hippocampal neurons. 

PMID- 24312005
TI  - Kv3.3b expression defines the shape of the complex spike in the Purkinje cell.
AB  - The complex spike (CS) in cerebellar Purkinje Cells (PC) is not an all-or-nothing
      phenomena as originally proposed, but shows variability depending on the spiking
      behavior of the Inferior Olive and intrinsic variability in the number and shape
      of spikelets. The potassium channel Kv3.3b, which has been proposed to undergo
      developmental changes during the postnatal PC maturation, has been shown to be
      crucial for the repolarization of the spikelets in the CS. We address here the
      regulation of the intrinsic CS variability by the expression of inactivating
      Kv3.3 channels in PCs by combining patch-clamp recordings and single-cell PCR
      methods on the same neurons, using a technique that we recently optimized to
      correlate single cell transcription levels with membrane ion channel
      electrophysiology. We show that while the inactivating TEA sensitive Kv3.3
      current peak intensity increases with postnatal age, the channel density does
      not, arguing against postnatal developmental changes of Kv3.3b expression. Real
      time PCR of Kv3.3b showed a high variability from cell to cell, correlated with
      the Kv3.3 current density, and suggesting that there are no mechanisms regulating
      these currents beyond the mRNA pool. We show a significant correlation between
      normalized quantity of Kv3.3b mRNA and both the number of CS spikelets and their
      rate of voltage fluctuation, linking the intrinsic CS shape directly to the
      Kv3.3b mRNA pool. Comparing the observed cell-to-cell variance with studies on
      transcriptional noise suggests that fluctuations of the Kv3.3b mRNA pool are
      possibly not regulated but represent merely transcriptional noise, resulting in
      intrinsic variability of the CS. 

PMID- 24312006
TI  - Neuroimmunity dynamics and the development of therapeutic strategies for
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder characterized
      by the progressive and selective loss of both upper and lower motoneurons. The
      neurodegenerative process is accompanied by a sustained inflammation in the brain
      and spinal cord. The neuron-immune interaction, implicating resident microglia of
      the central nervous system and blood-derived immune cells, is highly dynamic over
      the course of the disease. Here, we discuss the timely controlled neuroprotective
      and neurotoxic cues that are provided by the immune environment of motoneurons
      and their potential therapeutic applications for ALS. 

PMID- 24312007
TI  - Two open states of P2X receptor channels.
AB  - The occupancy of the orthosteric ligand binding sites of P2X receptor (P2XR)
      channels causes the rapid opening of a small cation-permeable pore, followed by a
      gradual dilation that renders the pore permeable to large organic cations.
      Electrophysiologically, this phenomenon was shown using whole-cell current
      recording on P2X2R-, P2X2/X5R-, P2X4R- and P2X7R-expressing cells that were
      bathed in N-methyl-D-glucamine (NMDG(+))-containing buffers in the presence
      and/or absence of small monovalent and divalent cations. The pore dilation of
      P2X4R and P2X7R caused a secondary current growth, whereas that of P2X2R showed a
      sustained kinetic coupling of dilation and desensitization, leading to receptor
      channel closure. The pore size of the P2X7R open and dilated states was estimated
      to be approximately 0.85 nm and greater than 1 nm, respectively. The P2XR pore
      dilation was also observed in intact cells by measurement of fluorescent dye
      uptake/release, application of polyethylene glycols of different sizes, and
      atomic force microscopy. However, pore dilation was not observed at the single
      channel level. Structural data describing the dilated state are not available,
      and the relevance of orthosteric and allosteric ligand interactions to pore
      dilation was not studied. 

PMID- 24312008
TI  - Neuroplasticity and the next wave of antidepressant strategies.
AB  - Depression is a common chronic psychiatric disorder that is also often co-morbid
      with numerous neurological and immune diseases. Accumulating evidence indicates
      that disturbances of neuroplasticity occur with depression, including reductions
      of hippocampal neurogenesis and cortical synaptogenesis. Improper trophic support
      stemming from stressor-induced reductions of growth factors, most notably brain
      derived neurotrophic factor (BDNF), likely drives such aberrant neuroplasticity.
      We posit that psychological and immune stressors can interact upon a vulnerable
      genetic background to promote depression by disturbing BDNF and neuroplastic
      processes. Furthermore, the chronic and commonly relapsing nature of depression
      is suggested to stem from "faulty wiring" of emotional circuits driven by
      neuroplastic aberrations. The present review considers depression in such terms
      and attempts to integrate the available evidence indicating that the efficacy of
      current and "next wave" antidepressant treatments, whether used alone or in
      combination, is at least partially tied to their ability to modulate
      neuroplasticity. We particularly focus on the N-methyl-D-aspartate (NMDA)
      antagonist, ketamine, which already has well documented rapid antidepressant
      effects, and the trophic cytokine, erythropoietin (EPO), which we propose as a
      potential adjunctive antidepressant agent. 

PMID- 24312010
TI  - miR-9: a versatile regulator of neurogenesis.
AB  - Soon after its discovery, microRNA-9 (miR-9) attracted the attention of
      neurobiologists, since it is one of the most highly expressed microRNAs in the
      developing and adult vertebrate brain. Functional analyses in different
      vertebrate species have revealed a prominent role of this microRNA in balancing
      proliferation in embryonic neural progenitor populations. Key transcriptional
      regulators such as FoxG1, Hes1 or Tlx, were identified as direct targets of miR
      9, placing it at the core of the gene network controlling the progenitor state.
      Recent data also suggest that this function could extend to adult neural stem
      cells. Other studies point to a role of miR-9 in differentiated neurons. Moreover
      miR-9 has been implicated in human brain pathologies, either displaying a
      protective role, such as in Progeria, or participating in disease progression in
      brain cancers. Altogether functional studies highlight a prominent feature of
      this highly conserved microRNA, its functional versatility, both along its
      evolutionary history and across cellular contexts. 

PMID- 24312009
TI  - Activity-dependent adaptations in inhibitory axons.
AB  - Synaptic connections in our brains change continuously and throughout our
      lifetime. Despite ongoing synaptic changes, a healthy balance between excitation
      and inhibition is maintained by various forms of homeostatic and activity
      dependent adaptations, ensuring stable functioning of neuronal networks. In this
      review we summarize experimental evidence for activity-dependent changes
      occurring in inhibitory axons, in cultures as well as in vivo. Axons form many
      presynaptic terminals, which are dynamic structures sharing presynaptic material
      along the axonal shaft. We discuss how internal (e.g., vesicle sharing) and
      external factors (e.g., binding of cell adhesion molecules or secreted factors)
      may affect the formation and plasticity of inhibitory synapses. 

PMID- 24312012
TI  - From Drosophila development to adult: clues to Notch function in long-term
      memory.
AB  - Notch is a cell surface receptor that is well known to mediate inter-cellular
      communication during animal development. Data in the field indicate that it is
      also involved in the formation of long-term memory (LTM) in the fully developed
      adults and in memory loss upon neurodegeneration. Our studies in the model
      organism Drosophila reveal that a non-canonical Notch-protein kinase C activity
      that plays critical roles in embryonic development also regulates cyclic-AMP
      response element binding protein during LTM formation in adults. Here we present
      a perspective on how the various known features of Notch function relate to LTM
      formation and how they might interface with elements of Wingless/Wnt signaling in
      this process. 

PMID- 24312011
TI  - Production and organization of neocortical interneurons.
AB  - Inhibitory GABA (gamma-aminobutyric acid)-ergic interneurons are a vital
      component of the neocortex responsible for shaping its output through a variety
      of inhibitions. Consisting of many flavors, interneuron subtypes are
      predominantly defined by their morphological, physiological, and neurochemical
      properties that help to determine their functional role within the neocortex.
      During development, these cells are born in the subpallium where they then
      tangentially migrate over long distances before being radially positioned to
      their final location in the cortical laminae. As development progresses into
      adolescence, these cells mature and form chemical and electrical connections with
      both glutamatergic excitatory neurons and other interneurons ultimately
      establishing the cortical network. The production, migration, and organization of
      these cells are determined by vast array of extrinsic and intrinsic factors that
      work in concert in order to assemble a proper functioning cortical inhibitory
      network. Failure of these cells to undergo these processes results in abnormal
      positioning and cortical function. In humans, this can bring about several
      neurological disorders including schizophrenia, epilepsy, and autism spectrum
      disorders. In this article, we will review previous literature that has revealed
      the framework for interneuron neurogenesis and migratory behavior as well as
      discuss recent findings that aim to elucidate the spatial and functional
      organization of interneurons within the neocortex. 

PMID- 24312013
TI  - Emerging links between homeostatic synaptic plasticity and neurological disease.
AB  - Homeostatic signaling systems are ubiquitous forms of biological regulation,
      having been studied for hundreds of years in the context of diverse physiological
      processes including body temperature and osmotic balance. However, only recently
      has this concept been brought to the study of excitatory and inhibitory
      electrical activity that the nervous system uses to establish and maintain stable
      communication. Synapses are a primary target of neuronal regulation with a
      variety of studies over the past 15 years demonstrating that these cellular
      junctions are under bidirectional homeostatic control. Recent work from an array
      of diverse systems and approaches has revealed exciting new links between
      homeostatic synaptic plasticity and a variety of seemingly disparate neurological
      and psychiatric diseases. These include autism spectrum disorders, intellectual
      disabilities, schizophrenia, and Fragile X Syndrome. Although the molecular
      mechanisms through which defective homeostatic signaling may lead to disease
      pathogenesis remain unclear, rapid progress is likely to be made in the coming
      years using a powerful combination of genetic, imaging, electrophysiological, and
      next generation sequencing approaches. Importantly, understanding homeostatic
      synaptic plasticity at a cellular and molecular level may lead to developments in
      new therapeutic innovations to treat these diseases. In this review we will
      examine recent studies that demonstrate homeostatic control of postsynaptic
      protein translation, retrograde signaling, and presynaptic function that may
      contribute to the etiology of complex neurological and psychiatric diseases. 

PMID- 24312015
TI  - The ontogeny of sleep-wake cycles in zebrafish: a comparison to humans.
AB  - Zebrafish (Danio rerio) are used extensively in sleep research; both to further
      understanding of sleep in general and also as a model of human sleep. To date,
      sleep studies have been performed in larval and adult zebrafish but no efforts
      have been made to document the ontogeny of zebrafish sleep-wake cycles. Because
      sleep differs across phylogeny and ontogeny it is important to validate the use
      of zebrafish in elucidating the neural substrates of sleep. Here we describe the
      development of sleep and wake across the zebrafish lifespan and how it compares
      to humans. We find power-law distributions to best fit wake bout data but
      demonstrate that exponential distributions, previously used to describe sleep
      bout distributions, fail to adequately account for the data in either species.
      Regardless, the data reveal remarkable similarities in the ontogeny of sleep
      cycles in zebrafish and humans. Moreover, as seen in other organisms, zebrafish
      sleep levels are highest early in ontogeny and sleep and wake bouts gradually
      consolidate to form the adult sleep pattern. Finally, sleep percentage, bout
      duration, bout number, and sleep fragmentation are shown to allow for meaningful
      comparisons between zebrafish and human sleep. 

PMID- 24312014
TI  - Introduction and perspective, historical note.
AB  - P2 nucleotide receptors were proposed to consist of two subfamilies based on
      pharmacology in 1985, named P2X and P2Y receptors. Later, this was confirmed
      following cloning of the receptors for nucleotides and studies of transduction
      mechanisms in the early 1990s. P2X receptors are ion channels and seven subtypes
      are recognized that form trimeric homomultimers or heteromultimers. P2X receptors
      are involved in neuromuscular and synaptic neurotransmission and neuromodulation.
      They are also expressed on many types of non-neuronal cells to mediate smooth
      muscle contraction, secretion, and immune modulation. The emphasis in this review
      will be on the pathophysiology of P2X receptors and therapeutic potential of P2X
      receptor agonists and antagonists for neurodegenerative and inflammatory
      disorders, visceral and neuropathic pain, irritable bowel syndrome, diabetes,
      kidney failure, bladder incontinence and cancer, as well as disorders if the
      special senses, airways, skin, cardiovascular, and musculoskeletal systems. 

PMID- 24312016
TI  - Vestibular blueprint in early vertebrates.
AB  - Central vestibular neurons form identifiable subgroups within the boundaries of
      classically outlined octavolateral nuclei in primitive vertebrates that are
      distinct from those processing lateral line, electrosensory, and auditory
      signals. Each vestibular subgroup exhibits a particular morpho-physiological
      property that receives origin-specific sensory inputs from semicircular canal and
      otolith organs. Behaviorally characterized phenotypes send discrete axonal
      projections to extraocular, spinal, and cerebellar targets including other ipsi-
      and contralateral vestibular nuclei. The anatomical locations of vestibuloocular
      and vestibulospinal neurons correlate with genetically defined hindbrain
      compartments that are well conserved throughout vertebrate evolution though some
      variability exists in fossil and extant vertebrate species. The different
      vestibular subgroups exhibit a robust sensorimotor signal processing complemented
      with a high degree of vestibular and visual adaptive plasticity. 

PMID- 24312017
TI  - Gain control of gamma frequency activation by a novel feed forward disinhibitory
      loop: implications for normal and epileptic neural activity.
AB  - The inhibition of excitatory (pyramidal) neurons directly dampens their activity
      resulting in a suppression of neural network output. The inhibition of inhibitory
      cells is more complex. Inhibitory drive is known to gate neural network
      synchrony, but there is also a widely held view that it may augment excitability
      by reducing inhibitory cell activity, a process termed disinhibition.
      Surprisingly, however, disinhibition has never been demonstrated to be an
      important mechanism that augments or drives the activity of excitatory neurons in
      a functioning neural circuit. Using voltage sensitive dye imaging (VSDI) we show
      that 20-80 Hz stimulus trains, beta-gamma activation, of the olfactory cortex
      pyramidal cells in layer II leads to a subsequent reduction in inhibitory
      interneuron activity that augments the efficacy of the initial stimulus. This
      disinhibition occurs with a lag of about 150-250 ms after the initial excitation
      of the layer 2 pyramidal cell layer. In addition, activation of the endopiriform
      nucleus also arises just before the disinhibitory phase with a lag of about 40-80
      ms. Preventing the spread of action potentials from layer II stopped the
      excitation of the endopiriform nucleus, abolished the disinhibitory activity, and
      reduced the excitation of layer II cells. After the induction of experimental
      epilepsy the disinhibition was more intense with a concomitant increase in
      excitatory cell activity. Our observations provide the first evidence of feed
      forward disinhibition loop that augments excitatory neurotransmission, a
      mechanism that could play an important role in the development of epileptic
      seizures. 

PMID- 24312018
TI  - Subthalamic nucleus long-range synchronization-an independent hallmark of human
      Parkinson's disease.
AB  - Beta-band synchronous oscillations in the dorsolateral region of the subthalamic
      nucleus (STN) of human patients with Parkinson's disease (PD) have been
      frequently reported. However, the correlation between STN oscillations and
      synchronization has not been thoroughly explored. The simultaneous recordings of
      2390 multi-unit pairs recorded by two parallel microelectrodes (separated by
      fixed distance of 2 mm, n = 72 trajectories with two electrode tracks >4 mm STN
      span) in 57 PD patients undergoing STN deep brain stimulation surgery were
      analyzed. Automatic procedures were utilized to divide the STN into dorsolateral
      oscillatory and ventromedial non-oscillatory regions, and to quantify the
      intensity of STN oscillations and synchronicity. Finally, the synchronicity of
      simultaneously vs. non-simultaneously recorded pairs were compared using a
      shuffling procedure. Synchronization was observed predominately in the beta range
      and only between multi-unit pairs in the dorsolateral oscillatory region (n =
      615). In paired recordings between sites in the dorsolateral and ventromedial (n
      = 548) and ventromedial-ventromedial region pairs (n = 1227), no synchronization
      was observed. Oscillation and synchronicity intensity decline along the STN
      dorsolateral-ventromedial axis suggesting a fuzzy border between the STN regions.
      Synchronization strength was significantly correlated to the oscillation power,
      but synchronization was no longer observed following shuffling. We conclude that
      STN long-range beta oscillatory synchronization is due to increased neuronal
      coupling in the Parkinsonian brain and does not merely reflect the outcome of
      oscillations at similar frequency. The neural synchronization in the dorsolateral
      (probably the motor domain) STN probably augments the pathological changes in
      firing rate and patterns of subthalamic neurons in PD patients. 

PMID- 24312019
TI  - Inter-laminar microcircuits across neocortex: repair and augmentation.

PMID- 24312020
TI  - Age-related sensitive periods influence visual language discrimination in adults.
AB  - Adults as well as infants have the capacity to discriminate languages based on
      visual speech alone. Here, we investigated whether adults' ability to
      discriminate languages based on visual speech cues is influenced by the age of
      language acquisition. Adult participants who had all learned English (as a first
      or second language) but did not speak French were shown faces of bilingual
      (French/English) speakers silently reciting sentences in either language. Using
      only visual speech information, adults who had learned English from birth or as a
      second language before the age of 6 could discriminate between French and English
      significantly better than chance. However, adults who had learned English as a
      second language after age 6 failed to discriminate these two languages,
      suggesting that early childhood exposure is crucial for using relevant visual
      speech information to separate languages visually. These findings raise the
      possibility that lowered sensitivity to non-native visual speech cues may
      contribute to the difficulties encountered when learning a new language in
      adulthood. 

PMID- 24312021
TI  - Neural and behavioral investigations into timbre perception.
AB  - Timbre is the attribute that distinguishes sounds of equal pitch, loudness and
      duration. It contributes to our perception and discrimination of different vowels
      and consonants in speech, instruments in music and environmental sounds. Here we
      begin by reviewing human timbre perception and the spectral and temporal acoustic
      features that give rise to timbre in speech, musical and environmental sounds. We
      also consider the perception of timbre by animals, both in the case of human
      vowels and non-human vocalizations. We then explore the neural representation of
      timbre, first within the peripheral auditory system and later at the level of the
      auditory cortex. We examine the neural networks that are implicated in timbre
      perception and the computations that may be performed in auditory cortex to
      enable listeners to extract information about timbre. We consider whether single
      neurons in auditory cortex are capable of representing spectral timbre
      independently of changes in other perceptual attributes and the mechanisms that
      may shape neural sensitivity to timbre. Finally, we conclude by outlining some of
      the questions that remain about the role of neural mechanisms in behavior and
      consider some potentially fruitful avenues for future research. 

PMID- 24312023
TI  - Magnetic tracking of eye position in freely behaving chickens.
AB  - Research on the visual system of non-primates, such as birds and rodents, is
      increasing. Evidence that neural responses can differ dramatically between head
      immobilized and freely behaving animals underlines the importance of studying
      visual processing in ethologically relevant contexts. In order to systematically
      study visual responses in freely behaving animals, an unobtrusive system for
      monitoring eye-in-orbit position in real time is essential. We describe a novel
      system for monitoring eye position that utilizes a head-mounted magnetic
      displacement sensor coupled with an eye-implanted magnet. This system is small,
      lightweight, and offers high temporal and spatial resolution in real time. We use
      the system to demonstrate the stability of the eye and the stereotypy of eye
      position during two different behavioral tasks in chickens. This approach offers
      a viable alternative to search coil and optical eye tracking techniques for high
      resolution tracking of eye-in-orbit position in behaving animals. 

PMID- 24312022
TI  - Learning, neural plasticity and sensitive periods: implications for language
      acquisition, music training and transfer across the lifespan.
AB  - Sensitive periods in human development have often been proposed to explain age
      related differences in the attainment of a number of skills, such as a second
      language (L2) and musical expertise. It is difficult to reconcile the negative
      consequence this traditional view entails for learning after a sensitive period
      with our current understanding of the brain's ability for experience-dependent
      plasticity across the lifespan. What is needed is a better understanding of the
      mechanisms underlying auditory learning and plasticity at different points in
      development. Drawing on research in language development and music training, this
      review examines not only what we learn and when we learn it, but also how
      learning occurs at different ages. First, we discuss differences in the mechanism
      of learning and plasticity during and after a sensitive period by examining how
      language exposure versus training forms language-specific phonetic
      representations in infants and adult L2 learners, respectively. Second, we
      examine the impact of musical training that begins at different ages on
      behavioral and neural indices of auditory and motor processing as well as
      sensorimotor integration. Third, we examine the extent to which childhood
      training in one auditory domain can enhance processing in another domain via the
      transfer of learning between shared neuro-cognitive systems. Specifically, we
      review evidence for a potential bi-directional transfer of skills between music
      and language by examining how speaking a tonal language may enhance music
      processing and, conversely, how early music training can enhance language
      processing. We conclude with a discussion of the role of attention in auditory
      learning for learning during and after sensitive periods and outline avenues of
      future research. 

PMID- 24312024
TI  - Habituation of reflexive and motivated behavior in mice with deficient BK channel
      function.
AB  - Habituation is considered the most basic form of learning. It describes the
      decrease of a behavioral response to a repeated non-threatening sensory stimulus
      and therefore provides an important sensory filtering mechanism. While some
      neuronal pathways mediating habituation are well described, underlying
      cellular/molecular mechanisms are not yet fully understood. In general, there is
      an agreement that short-term and long-term habituation are based on different
      mechanisms. Historically, a distinction has also been made between habituation of
      motivated versus reflexive behavior. In recent studies in invertebrates the large
      conductance voltage- and calcium-activated potassium (BK) channel has been
      implicated to be a key player in habituation by regulating synaptic transmission.
      Here, we tested mice deficient for the pore forming alpha-subunit of the BK
      channel for short-term and long-term habituation of the acoustic startle reflex
      (reflexive behavior) and of the exploratory locomotor behavior in the open field
      box (motivated behavior). Short-term habituation of startle was completely
      abolished in the BK knock-out mice, whereas neither long-term habituation of
      startle nor habituation of motivated behavior was affected by the BK deficiency.
      Our results support a highly preserved mechanism for short-term habituation of
      startle across species that is distinct from long-term habituation mechanisms. It
      also supports the notion that there are different mechanisms underlying
      habituation of motivated behavior versus reflexive behavior. 

PMID- 24312025
TI  - The three principles of action: a Pavlovian-instrumental transfer hypothesis.
AB  - Pavlovian conditioned stimuli can influence instrumental responding, an effect
      called Pavlovian-instrumental transfer (PIT). During the last decade, PIT has
      been subdivided into two types: specific PIT and general PIT, each having its own
      neural substrates. Specific PIT happens when a conditioned stimulus (CS)
      associated with a reward enhances an instrumental response directed to the same
      reward. Under general PIT, instead, the CS enhances a response directed to a
      different reward. While important progress has been made into identifying the
      neural substrates, the function of specific and general PIT and how they interact
      with instrumental responses are still not clear. In the experimental paradigm
      that distinguishes specific and general PIT an effect of PIT inhibition has also
      been observed and is waiting for an explanation. Here we propose an hypothesis
      that links these three PIT effects (specific PIT, general PIT and PIT inhibition)
      to three aspects of action evaluation. These three aspects, which we call
      "principles of action", are: context, efficacy, and utility. In goal-directed
      behavior, an agent has to evaluate if the context is suitable to accomplish the
      goal, the efficacy of his action in getting the goal, and the utility of the goal
      itself: we suggest that each of the three PIT effects is related to one of these
      aspects of action evaluation. In particular, we link specific PIT with the
      estimation of efficacy, general PIT with the evaluation of utility, and PIT
      inhibition with the adequacy of context. We also provide a latent cause Bayesian
      computational model that exemplifies this hypothesis. This hypothesis and the
      model provide a new framework and new predictions to advance knowledge about PIT
      functioning and its role in animal adaptation. 

PMID- 24312026
TI  - Decanalization mediating gene-environment interactions in schizophrenia and other
      psychiatric disorders with neurodevelopmental etiology.

PMID- 24312027
TI  - Male mice emit distinct ultrasonic vocalizations when the female leaves the
      social interaction arena.
AB  - Adult male mice emit large number of complex ultrasonic vocalizations (USVs) when
      interacting with adult females. Call numbers and call categories differ greatly
      among inbred mouse strains. Little is known about USV emissions when the social
      partner departs. To investigate whether call repertoires and call rates are
      different when the male is interacting with a female and after the removal of the
      female, we designed a novel male-female social interaction test in which
      vocalizations were recorded across three phases. During phase 1, the male subject
      freely interacts with an unfamiliar estrus female mouse in a clean cage for 5
      min. During phase 2, the female is removed while the male remains in the cage for
      3 min. During phase 3, the same female is returned to the cage to rejoin the male
      subject mouse for 3 min. C57BL/6J (B6), FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant (FVB),
      and BTBR T+ tf/J (BTBR) male subject mice were tested in this paradigm. All three
      strains emitted USVs during their initial interaction with the female partner.
      When the female was reintroduced in phase 3, numbers of USVs were similar to the
      initial introductory phase 1. Strain comparisons indicated fewer calls in pairs
      of BTBR males and stimulus females than in pairs of B6 males and stimulus females
      and pairs of FVB males and stimulus females. In the absence of the female, all
      FVB males vocalized, while only one third of B6 males and one third of BTBR males
      vocalized. In all three strains, changes in call category repertoires were
      detected after the female was removed. Call categories reverted to the phase 1
      pattern when the female was returned in phase 3. Present findings indicate that
      males of commonly used inbred strains emit USVs when a partner female leaves the
      testing arena, suggesting that removing a salient social stimulus may be a unique
      approach to elicit USVs from mice. Our three-phase paradigm may also be useful
      for studying attention to social cues, and qualitative differences in
      vocalizations when a social partner is present vs. suddenly absent. 

PMID- 24312028
TI  - The influence of the noradrenergic system on optimal control of neural
      plasticity.
AB  - Decision making under uncertainty is challenging for any autonomous agent. The
      challenge increases when the environment's stochastic properties change over
      time, i.e., when the environment is volatile. In order to efficiently adapt to
      volatile environments, agents must primarily rely on recent outcomes to quickly
      change their decision strategies; in other words, they need to increase their
      knowledge plasticity. On the contrary, in stable environments, knowledge
      stability must be preferred to preserve useful information against noise. Here we
      propose that in mammalian brain, the locus coeruleus (LC) is one of the nuclei
      involved in volatility estimation and in the subsequent control of neural
      plasticity. During a reinforcement learning task, LC activation, measured by
      means of pupil diameter, coded both for environmental volatility and learning
      rate. We hypothesize that LC could be responsible, through norepinephrinic
      modulation, for adaptations to optimize decision making in volatile environments.
      We also suggest a computational model on the interaction between the anterior
      cingulate cortex (ACC) and LC for volatility estimation. 

PMID- 24312030
TI  - Reinforcement and inference in cross-situational word learning.
AB  - Cross-situational word learning is based on the notion that a learner can
      determine the referent of a word by finding something in common across many
      observed uses of that word. Here we propose an adaptive learning algorithm that
      contains a parameter that controls the strength of the reinforcement applied to
      associations between concurrent words and referents, and a parameter that
      regulates inference, which includes built-in biases, such as mutual exclusivity,
      and information of past learning events. By adjusting these parameters so that
      the model predictions agree with data from representative experiments on cross
      situational word learning, we were able to explain the learning strategies
      adopted by the participants of those experiments in terms of a trade-off between
      reinforcement and inference. These strategies can vary wildly depending on the
      conditions of the experiments. For instance, for fast mapping experiments (i.e.,
      the correct referent could, in principle, be inferred in a single observation)
      inference is prevalent, whereas for segregated contextual diversity experiments
      (i.e., the referents are separated in groups and are exhibited with members of
      their groups only) reinforcement is predominant. Other experiments are explained
      with more balanced doses of reinforcement and inference. 

PMID- 24312031
TI  - Neural correlates of risk perception: HIV vs. leukemia.
AB  - Field studies on HIV risk perception suggest that people may rely on impressions
      they have about the safety of their partner. Previous studies show that
      individuals perceived as "risky" regarding HIV elicit a differential brain
      response in both earlier (~200-350 ms) and later (~350-700 ms) time windows
      compared to those perceived as safe. This raises the question whether this event
      related brain potential (ERP) response is specific to contagious life-threatening
      diseases or a general mechanism triggered by life-threatening but non-contagious
      diseases. In the present study, we recorded dense sensor EEG while participants
      (N = 36) evaluated photographs of unacquainted individuals for either HIV or
      leukemia risk. The ERP results replicated previous findings revealing earlier and
      later differential brain responses towards individuals perceived as high risk for
      HIV. However, there were no significant ERP differences for high vs. low leukemia
      risk. Rather than reflecting a generic response to disease, the present findings
      suggest that intuitive judgments of HIV risk are at least in part specific to
      sexually transmitted diseases. 

PMID- 24312032
TI  - Optogenetics, physiology, and emotions.

PMID- 24312033
TI  - Hyperactivity, perseveration and increased responding during attentional rule
      acquisition in the Fragile X mouse model.
AB  - Attentional deficits and executive function impairments are common to many
      neurodevelopmental disorders of intellectual disability and autism, including
      Fragile X syndrome (FXS). In the knockout mouse model for FXS, significant
      changes in synaptic plasticity and connectivity are found in the prefrontal
      cortex (PFC)-a prominent region for attentional processing and executive control.
      Given these alterations in PFC synaptic function, we tested whether adult Fragile
      X knockout mice exhibited corresponding impairments in inhibitory control,
      perseveration, and sustained attention. Furthermore, we investigated individual
      performance during attentional rule acquisition. Using the 5-choice serial
      reaction time task, our results show no impairments in inhibitory control and
      sustained attention. Fragile X knockout mice exhibited enhanced levels of correct
      and incorrect responding, as well as perseveration of responding during initial
      phases of rule acquisition, that normalized with training. For both knockout and
      wild type mice, pharmacological attenuation of metabotropic glutamate receptor 5
      signaling did not affect response accuracy but reduced impulsive responses and
      increased omission errors. Upon rule reversal, Fragile X knockout mice made more
      correct and incorrect responses, similar to the initial phases of rule
      acquisition. Analogous to heightened activity upon novel rule acquisition,
      Fragile X knockout mice were transiently hyperactive in both a novel open field
      (OF) arena and novel home cage. Hyperactivity ceased with familiarization to the
      environment. Our findings demonstrate normal inhibitory control and sustained
      attention but heightened perseveration, responding, and hyperactivity during
      novel rule acquisition and during exposure to novel environments in Fragile X
      knockout mice. We therefore provide evidence for subtle but significant
      differences in the processing of novel stimuli in the mouse model for the FXS. 

PMID- 24312029
TI  - Associative learning beyond the medial temporal lobe: many actors on the memory
      stage.
AB  - Decades of research have established a model that includes the medial temporal
      lobe, and particularly the hippocampus, as a critical node for episodic memory.
      Neuroimaging and clinical studies have shown the involvement of additional
      cortical and subcortical regions. Among these areas, the thalamus, the
      retrosplenial cortex, and the prefrontal cortices have been consistently related
      to episodic memory performance. This article provides evidences that these areas
      are in different forms and degrees critical for human memory function rather than
      playing only an ancillary role. First we briefly summarize the functional
      architecture of the medial temporal lobe with respect to recognition memory and
      recall. We then focus on the clinical and neuroimaging evidence available on
      thalamo-prefrontal and thalamo-retrosplenial networks. The role of these networks
      in episodic memory has been considered secondary, partly because disruption of
      these areas does not always lead to severe impairments; to account for this
      evidence, we discuss methodological issues related to the investigation of these
      regions. We propose that these networks contribute differently to recognition
      memory and recall, and also that the memory stage of their contribution shows
      specificity to encoding or retrieval in recall tasks. We note that the same
      mechanisms may be in force when humans perform non-episodic tasks, e.g., semantic
      retrieval and mental time travel. Functional disturbance of these networks is
      related to cognitive impairments not only in neurological disorders, but also in
      psychiatric medical conditions, such as schizophrenia. Finally we discuss
      possible mechanisms for the contribution of these areas to memory, including
      regulation of oscillatory rhythms and long-term potentiation. We conclude that
      integrity of the thalamo-frontal and the thalamo-retrosplenial networks is
      necessary for the manifold features of episodic memory. 

PMID- 24312034
TI  - On the evolution of the serotonin transporter linked polymorphic region (5
      HTTLPR) in primates.
AB  - Some allelic variants of the serotonin transporter linked polymorphic region (5
      HTTLPR) result in lower levels of expression of the serotonin transporter gene
      (SLC6A4). These low-expressing (LE) alleles are associated with mental-health
      disorders in a minority of humans that carry them. Humans are not the only
      primates that exhibit this polymorphism; other species, including some monkeys,
      also have LE and high-expressing (HE) variants of 5-HTTLPR. We propose a
      behavioral genetic framework to explain the adaptive evolution of this
      polymorphism in primates, including humans. We hypothesize that both LE and HE
      alleles are maintained by balancing selection in species characterized by short
      term fluctuations in social competition levels. More specifically, we propose
      that LE carriers benefit from their hypervigilant tendencies during periods of
      elevated competition, whereas HE homozygotes cope best when competition levels do
      not deviate from the norm. Thus, both alleles have long-term benefits when
      competition levels tend to vary substantially over relatively short timescales
      within a social group. We describe this hypothesis in detail and outline a series
      of predictions to test it. Some of these predictions are supported by findings in
      the current literature, while others remain areas of future research. 

PMID- 24312035
TI  - A longitudinal study of grapheme-color synesthesia in childhood: 6/7 years to
      10/11 years.
AB  - Grapheme-color synesthesia is a condition characterized by enduring and
      consistent associations between letter/digits and colors. This study is the
      continuation of longitudinal research begun by Simner et al. (2009) which aimed
      to explore the development of this condition in real time within a childhood
      population. In that earlier study we randomly sampled over 600 children and
      tested them aged 6/7 and 7/8 years. We identified the child synesthetes within
      that cohort and measured their development over 1 year, in comparison to a group
      of non-synesthetic children with both average and superior memories. We were able
      to show the beginnings of a developmental progression in which synesthetic
      associations (e.g., A = red) mature over time from relatively chaotic pairings
      into a system of fixed consistent associations. In the current study we return to
      this same population three years later when participants are now 10/11 years. We
      used the same paired-association memory task to determine the synesthetic status
      of our participants and to also establish synesthetes' inventories of grapheme
      color associations. We compared their inventories to those from age 6/7 and 7/8
      years to examine how synesthesia matures over time. Together with earlier
      findings, our study shows that grapheme-color synesthesia emerges with a
      protracted trajectory, with 34% of letters/digits fixed at age 6/7 years, 48%
      fixed at 7/8 years and 71% fixed at 10/11 years. We also show several cases where
      synesthesia is not developing in the same time-frame as peers, either because it
      has died out at an older age, or because it was slower to develop than other
      cases. Our study paints the first picture of the emergence of synesthesia in real
      time over four years within a randomly sampled population of child synesthetes. 

PMID- 24312036
TI  - The delay effect on outcome evaluation: results from an event-related potential
      study.
AB  - Behavioral studies demonstrate that the timing of receiving gains or losses
      affects decision-making, a phenomenon known as temporal discounting, as
      participants are inclined to prefer immediate rewards over delayed ones and vice
      versa for losses. The present study used the event-related potential technique
      with a simple gambling task to investigate how delayed rewards and losses
      affected the brain activity in outcome evaluations made by 20 young adults.
      Statistical analysis revealed a larger feedback-related negativity (FRN) effect
      between loss and gain following immediate outcomes than following future
      outcomes. In addition, delay impacted FRN only in gain conditions, with delayed
      winning eliciting a more negative FRN than immediate winning. These results
      suggest that temporal discounting and sign effect could be encoded in the FRN in
      the early stage of outcome evaluation. 

PMID- 24312037
TI  - Learning fast accurate movements requires intact frontostriatal circuits.
AB  - The basal ganglia are known to play a crucial role in movement execution, but
      their importance for motor skill learning remains unclear. Obstacles to our
      understanding include the lack of a universally accepted definition of motor
      skill learning (definition confound), and difficulties in distinguishing learning
      deficits from execution impairments (performance confound). We studied how
      healthy subjects and subjects with a basal ganglia disorder learn fast accurate
      reaching movements. We addressed the definition and performance confounds by: (1)
      focusing on an operationally defined core element of motor skill learning (speed
      accuracy learning), and (2) using normal variation in initial performance to
      separate movement execution impairment from motor learning abnormalities. We
      measured motor skill learning as performance improvement in a reaching task with
      a speed-accuracy trade-off. We compared the performance of subjects with
      Huntington's disease (HD), a neurodegenerative basal ganglia disorder, to that of
      premanifest carriers of the HD mutation and of control subjects. The initial
      movements of HD subjects were less skilled (slower and/or less accurate) than
      those of control subjects. To factor out these differences in initial execution,
      we modeled the relationship between learning and baseline performance in control
      subjects. Subjects with HD exhibited a clear learning impairment that was not
      explained by differences in initial performance. These results support a role for
      the basal ganglia in both movement execution and motor skill learning. 

PMID- 24312038
TI  - Enhanced antisaccade abilities in children with Tourette syndrome: the Gap-effect
      Reversal.
AB  - Tourette Syndrome (TS) is a childhood onset disorder of motor and vocal tics. The
      neural networks underlying TS overlap with those of saccade eye movements. Thus,
      deviations on saccadic tasks can provide important information about
      psychopathology of TS. Tourette syndrome often coexists with Attention Deficit
      Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD). Hence, we
      manipulated various components of a saccade task to measure its effects on
      saccades of children with TS-only, TS+ADHD, TS+ADHD+OCD and healthy controls.
      Children looked toward (prosaccade) or in the opposite direction (antisaccade) of
      a peripheral target as soon as it appeared. The prosaccade and antisaccade tasks
      were presented in three conditions. In the Gap200 condition, the fixation dot
      disappeared 200 ms prior to the appearance of the peripheral target, In the
      Gap800 condition, the fixation dot disappeared 800 ms prior to the appearance of
      the peripheral target and in Overlap200 the fixation dot disappeared 200 ms after
      the appearance of the peripheral target. Fixation-offset manipulations had
      different effects on each group's antisaccades. The TS+ADHD+OCD group's
      antisaccade latencies and error rates remained relatively unchanged in the three
      conditions and displayed a pattern of eye movements that can be interpreted as
      enhanced. Alternatively, the TS+ADHD group displayed an overall pattern of longer
      saccadic latencies. Findings corroborate the hypothesis that the combination of
      tic disorder and ADHD results in unique behavioral profiles. It is plausible that
      a subgroup of children with TS develop an adaptive ability to control their tics
      which generalizes to enhanced volitional control of saccadic behavior as well.
      Supporting evidence and other findings are discussed. 

PMID- 24312039
TI  - The economy of social resources and its influence on spatial perceptions.
AB  - Survival for any organism, including people, is a matter of resource management.
      To ensure survival, people necessarily budget their resources. Spatial
      perceptions contribute to resource budgeting by scaling the environment to an
      individual's available resources. Effective budgeting requires setting a balance
      of income and expenditures around some baseline value. For social resources, this
      baseline assumes that the individuals are embedded in their social network. A
      review of the literature supports the proposal that our visual perceptions vary
      based on the implicit budgeting of physical and social resources, where social
      resources, as they fluctuate relative to a baseline, can directly alter our
      visual perceptions. 

PMID- 24312041
TI  - On ERPs detection in disorders of consciousness rehabilitation.
AB  - Disorders of Consciousness (DOC) like Vegetative State (VS), and Minimally
      Conscious State (MCS) are clinical conditions characterized by the absence or
      intermittent behavioral responsiveness. A neurophysiological monitoring of
      parameters like Event-Related Potentials (ERPs) could be a first step to follow
      up the clinical evolution of these patients during their rehabilitation phase.
      Eleven patients diagnosed as VS (n = 8) and MCS (n = 3) by means of the JFK Coma
      Recovery Scale Revised (CRS-R) underwent scalp EEG recordings during the delivery
      of a 3-stimuli auditory oddball paradigm, which included standard, deviant tones
      and the subject own name (SON) presented as a novel stimulus, administered under
      passive and active conditions. Four patients who showed a change in their
      clinical status as detected by means of the CRS-R (i.e., moved from VS to MCS),
      were subjected to a second EEG recording session. All patients, but one (anoxic
      etiology), showed ERP components such as mismatch negativity (MMN) and novelty
      P300 (nP3) under passive condition. When patients were asked to count the novel
      stimuli (active condition), the nP3 component displayed a significant increase in
      amplitude (p = 0.009) and a wider topographical distribution with respect to the
      passive listening, only in MCS. In 2 out of the 4 patients who underwent a second
      recording session consistently with their transition from VS to MCS, the nP3
      component elicited by passive listening of SON stimuli revealed a significant
      amplitude increment (p < 0.05). Most relevant, the amplitude of the nP3 component
      in the active condition, acquired in each patient and in all recording sessions,
      displayed a significant positive correlation with the total scores (p = 0.004)
      and with the auditory sub-scores (p < 0.00001) of the CRS-R administered before
      each EEG recording. As such, the present findings corroborate the value of ERPs
      monitoring in DOC patients to investigate residual unconscious and conscious
      cognitive function. 

PMID- 24312042
TI  - Functionally distinct contributions of the anterior and posterior putamen during
      sublexical and lexical reading.
AB  - Previous studies have investigated orthographic-to-phonological mapping during
      reading by comparing brain activation for (1) reading words to object naming, or
      (2) reading pseudowords (e.g., "phume") to words (e.g., "plume"). Here we
      combined both approaches to provide new insights into the underlying neural
      mechanisms. In fMRI data from 25 healthy adult readers, we first identified
      activation that was greater for reading words and pseudowords relative to picture
      and color naming. The most significant effect was observed in the left putamen,
      extending to both anterior and posterior borders. Second, consistent with
      previous studies, we show that both the anterior and posterior putamen are
      involved in articulating speech with greater activation during our overt speech
      production tasks (reading, repetition, object naming, and color naming) than
      silent one-back-matching on the same stimuli. Third, we compared putamen
      activation for words versus pseudowords during overt reading and auditory
      repetition. This revealed that the anterior putamen was most activated by reading
      pseudowords, whereas the posterior putamen was most activated by words
      irrespective of whether the task was reading words or auditory word repetition.
      The pseudoword effect in the anterior putamen is consistent with prior studies
      that associated this region with the initiation of novel sequences of movements.
      In contrast, the heightened word response in the posterior putamen is consistent
      with other studies that associated this region with "memory guided movement." Our
      results illustrate how the functional dissociation between the anterior and
      posterior putamen supports sublexical and lexical processing during reading. 

PMID- 24312040
TI  - Does docosahexaenoic acid supplementation in term infants enhance neurocognitive
      functioning in infancy?
AB  - The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive
      functioning in term infants is controversial. Theoretical evidence, laboratory
      research and human epidemiological studies have convincingly demonstrated that
      DHA deficiency can negatively impact neurocognitive development. However, the
      results from randomized controlled trials (RCTs) of DHA supplementation in human
      term-born infants have been inconsistent. This article will (i) discuss the role
      of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA
      plausibly influences neurocognitive capacity, and (iii) seek to characterize the
      optimal intake of DHA during infancy for neurocognitive functioning, based on
      existing research that has been undertaken in developed countries (specifically,
      within Australia). The major observational studies and RCTs that have examined
      dietary DHA in human infants and animals are presented, and we consider
      suggestions that DHA requirements vary across individuals according to genetic
      profile. It is important that the current evidence concerning DHA supplementation
      is carefully evaluated so that appropriate recommendations can be made and future
      directions of research can be strategically planned. 

PMID- 24312043
TI  - The effect of breakfast cereal consumption on adolescents' cognitive performance
      and mood.
AB  - The aim of the current study was to investigate the effect of breakfast
      consumption on cognitive performance and mood in adolescents, and any interaction
      that breakfast consumption might have with cognitive load. The rationale for this
      approach was that the beneficial effects of any intervention with regard to
      cognitive function may be more readily apparent when more demands are placed on
      the system. Furthermore, as skipping breakfast is particularly prevalent within
      this age group, thus, we focused on adolescents who habitually skip breakfast.
      Cognitive load was modulated by varying the level of difficulty of a series of
      cognitive tasks tapping memory, attention, and executive functions. Mood measured
      with Bond-Lader scales (1974) as well as measures of thirst, hunger, and satiety
      were recorded at each test session both at baseline and after the completion of
      each test battery. Forty adolescents (mean age = 14:2) participated in this
      within-subjects design study. According to treatment, all participants were
      tested before and after the intake of a low Glycaemic index breakfast (i.e., a 35
      g portion of AllBran and 125 ml semi-skimmed milk) and before and after no
      breakfast consumption. Assessment time had two levels: 8.00 am (baseline) and
      10.45 am. The orders of cognitive load tasks were counterbalanced. Overall it
      appeared that following breakfast participants felt more alert, satiated, and
      content. Following breakfast consumption, there was evidence for improved
      cognitive performance across the school morning compared to breakfast omission in
      some tasks (e.g., Hard Word Recall, Serial 3's and Serial 7's). However, whilst
      participants performance on the hard version of each cognitive task was
      significantly poorer compared to the corresponding easy version, there was
      limited evidence to support the hypothesis that the effect of breakfast was
      greater in the more demanding versions of the tasks. 

PMID- 24312044
TI  - Motor imagery ability in stroke patients: the relationship between implicit and
      explicit motor imagery measures.
AB  - There is little consensus on how motor imagery ability should be measured in
      stroke patients. In particular it is unclear how two methods tapping different
      aspects of the motor imagery process relate to each other. The aim of this study
      was to investigate the relationship between implicit and explicit motor imagery
      ability by comparing performance of stroke patients and controls on a motor
      imagery questionnaire and a hand laterality judgment task (HLJT). Sixteen
      ischemic stroke patients (36 +/- 13 weeks post-stroke) and 16 controls, matched
      by age (51 +/- 10 years), gender (7 females) and handedness (3 left-handed),
      performed a HLJT and completed a motor imagery questionnaire. Our study shows
      that neither in the healthy controls nor in patients, a correlation is found
      between the HLJT and the motor imagery questionnaire. Although the patient group
      scored significantly lower than the control group on the visual motor imagery
      component (U = 60; p = 0.010) and the kinesthetic motor imagery component (U =
      63.5; p = 0.015) of the questionnaire, there were no significant differences
      between patients and controls on accuracy scores of the HLJT. Analyses of the
      reaction time profiles of patients and controls showed that patient were still
      able to use an implicit motor imagery strategy in the HLJT task. Our results show
      that after stroke performance on tests that measure two different aspects of
      motor imagery ability, e.g., implicit and explicit motor imagery, can be
      differently affected. These results articulate the complex relation
      phenomenological experience and the different components of motor imagery have
      and caution the use of one tool as an instrument for use in screening, selecting
      and monitoring stroke patients in rehabilitation settings. 

PMID- 24312045
TI  - Spatio-temporal analysis reveals active control of both task-relevant and task
      irrelevant variables.
AB  - The Uncontrolled Manifold (UCM) hypothesis and Minimal Intervention principle
      propose that the observed differential variability across task relevant (i.e.,
      task goals) vs. irrelevant (i.e., in the null space of those goals) variables is
      evidence of a separation of task variables for efficient neural control, ranked
      by their respective variabilities (sometimes referred to as hierarchy of
      control). Support for this comes from spatial domain analyses (i.e., structure
      of) of kinematic, kinetic, and EMG variability. While proponents admit the
      possibility of preferential as opposed to strictly uncontrolled variables, such
      distinctions have only begun to be quantified or considered in the temporal
      domain when inferring control action. Here we extend the study of task
      variability during tripod static grasp to the temporal domain by applying
      diffusion analysis. We show that both task-relevant and task-irrelevant
      parameters show corrective action at some time scales; and conversely, that task
      relevant parameters do not show corrective action at other time scales. That is,
      the spatial fluctuations of fingertip forces show, as expected, greater ranges of
      variability in task-irrelevant variables (>98% associated with changes in total
      grasp force; vs. only <2% in task-relevant changes associated with acceleration
      of the object). But at some time scales, however, temporal fluctuations of task
      irrelevant variables exhibit negative correlations clearly indicative of
      corrective action (scaling exponents <0.5); and temporal fluctuations of task
      relevant variables exhibit neutral and positive correlations clearly indicative
      of absence of corrective action (scaling exponents >=0.5). In agreement with
      recent work in other behavioral contexts, these results propose we revise our
      understanding of variability vis-a-vis task relevance by considering both spatial
      and temporal features of all task variables when inferring control action and
      understanding how the CNS confronts task redundancy. Instead of a dichotomy of
      presence vs. absence of control, we should speak of a continuum of weaker to
      stronger-and potentially different-control strategies in specific spatiotemporal
      domains, indicated here by the magnitude of deviation from the 0.5 scaling
      exponent. Moreover, these results are counter examples to the UCM hypothesis and
      the Minimal Intervention principle, and the similar nature of control actions
      across time scales in both task-relevant and task-irrelevant spaces points to a
      level of modularity not previously recognized. 

PMID- 24312046
TI  - Computational modeling of the negative priming effect based on inhibition
      patterns and working memory.
AB  - Negative priming (NP), slowing down of the response for target stimuli that have
      been previously exposed, but ignored, has been reported in multiple psychological
      paradigms including the Stroop task. Although NP likely results from the
      interplay of selective attention, episodic memory retrieval, working memory, and
      inhibition mechanisms, a comprehensive theoretical account of NP is currently
      unavailable. This lacuna may result from the complexity of stimuli combinations
      in NP. Thus, we aimed to investigate the presence of different degrees of the NP
      effect according to prime-probe combinations within a classic Stroop task. We
      recorded reaction times (RTs) from 66 healthy participants during Stroop task
      performance and examined three different NP subtypes, defined according to the
      type of the Stroop probe in prime-probe pairs. Our findings show significant RT
      differences among NP subtypes that are putatively due to the presence of
      differential disinhibition, i.e., release from inhibition. Among the several
      potential origins for differential subtypes of NP, we investigated the
      involvement of selective attention and/or working memory using a parallel
      distributed processing (PDP) model (employing selective attention only) and a
      modified PDP model with working memory (PDP-WM, employing both selective
      attention and working memory). Our findings demonstrate that, unlike the
      conventional PDP model, the PDP-WM successfully simulates different levels of NP
      effects that closely follow the behavioral data. This outcome suggests that
      working memory engages in the re-accumulation of the evidence for target response
      and induces differential NP effects. Our computational model complements earlier
      efforts and may pave the road to further insights into an integrated theoretical
      account of complex NP effects. 

PMID- 24312047
TI  - Theta-specific susceptibility in a model of adaptive synaptic plasticity.
AB  - Learning and memory formation are processes which are still not fully understood.
      It is widely believed that synaptic plasticity is the most important neural
      substrate for both. However, it has been observed that large-scale theta band
      oscillations in the mammalian brain are beneficial for learning, and it is not
      clear if and how this is linked to synaptic plasticity. Also, the underlying
      dynamics of synaptic plasticity itself have not been completely uncovered yet,
      especially for non-linear interactions between multiple spikes. Here, we present
      a new and simple dynamical model of synaptic plasticity. It incorporates novel
      contributions to synaptic plasticity including adaptation processes. We test its
      ability to reproduce non-linear effects on four different data sets of complex
      spike patterns, and show that the model can be tuned to reproduce the observed
      synaptic changes in great detail. When subjected to periodically varying firing
      rates, already linear pair based spike timing dependent plasticity (STDP)
      predicts a specific susceptibility of synaptic plasticity to pre- and
      postsynaptic firing rate oscillations in the theta-band. Our model retains this
      band-pass property, while for high firing rates in the non-linear regime it
      modifies the specific phase relation required for depression and potentiation.
      For realistic parameters, maximal synaptic potentiation occurs when the
      postsynaptic is trailing the presynaptic activity slightly. Anti-phase
      oscillations tend to depress it. Our results are well in line with experimental
      findings, providing a straightforward and mechanistic explanation for the
      importance of theta oscillations for learning. 

PMID- 24312048
TI  - Disruption of transfer entropy and inter-hemispheric brain functional
      connectivity in patients with disorder of consciousness.
AB  - Severe traumatic brain injury can lead to disorders of consciousness (DOC)
      characterized by deficit in conscious awareness and cognitive impairment
      including coma, vegetative state, minimally consciousness, and lock-in syndrome.
      Of crucial importance is to find objective markers that can account for the large
      scale disturbances of brain function to help the diagnosis and prognosis of DOC
      patients and eventually the prediction of the coma outcome. Following recent
      studies suggesting that the functional organization of brain networks can be
      altered in comatose patients, this work analyzes brain functional connectivity
      (FC) networks obtained from resting-state functional magnetic resonance imaging
      (rs-fMRI). Two approaches are used to estimate the FC: the Partial Correlation
      (PC) and the Transfer Entropy (TE). Both the PC and the TE show significant
      statistical differences between the group of patients and control subjects; in
      brief, the inter-hemispheric PC and the intra-hemispheric TE account for such
      differences. Overall, these results suggest two possible rs-fMRI markers useful
      to design new strategies for the management and neuropsychological rehabilitation
      of DOC patients. 

PMID- 24312049
TI  - Effects of antiepileptic drugs on hippocampal neurons coupled to micro-electrode
      arrays.
AB  - Hippocampal networks exhibit spontaneous electrophysiological activity that can
      be modulated by pharmacological manipulation and can be monitored over time using
      Micro-Electrode Arrays (MEAs), devices composed by a glass substrate and metal
      electrodes. The typical mode of activity of these dissociated cultures is the
      network-wide bursting pattern, which, if properly chemically modulated, can
      recall the ictal events of the epileptic phenotypes and is well-suited to study
      the effects of antiepileptic compounds. In this paper, we analyzed the changes
      induced by Carbamazepine (CBZ) and Valproate (VPA) on mature networks of
      hippocampal neurons in "control" condition (i.e., in the culturing medium) and
      upon treatment with the pro-convulsant bicuculline (BIC). We found that, in both
      control and BIC-treated networks, high doses (100 MUM-1 mM) of CBZ almost
      completely suppressed the spiking and bursting activity of hippocampal neurons.
      On the contrary, VPA never completely abolish the electrophysiological activity
      in both experimental designs. Interestingly, VPA cultures pre-treated with BIC
      showed dual effects. In fact, in some cultures, at low VPA concentrations (100 nM
      1 MUM), we observed decreased firing/bursting levels, which returned to values
      comparable to BIC-evoked activity at high VPA concentrations (100 MUM-1 mM). In
      other cultures, VPA reduced BIC-evoked activity in a concentration-independent
      manner. In conclusion, our study demonstrates that MEA-coupled hippocampal
      networks are responsive to chemical manipulations and, upon proper
      pharmacological modulation, might provide model systems to detect acute
      pharmacological effects of antiepileptic drugs. 

PMID- 24312050
TI  - Age-dependent changes in the histogram of apparent diffusion coefficients values
      in magnetic resonance imaging.
AB  - The aim of this study was to develop a fast method for estimating whether a brain
      volume loss is within the normal range for the respective age of the patient. A
      readout-segmented diffusion-weighted echo-planar imaging sequence was performed
      as part of the routine examination at a 3-T scanner. Data without (b0-image) and
      with diffusion weighting (1000 s/mm(2)) from 492 patients were examined (in the
      age from 3 to 89 years). One hundred and seventy-three data-sets had to be
      excluded due to brain lesions or to pathological enlarged cerebrospinal fluid
      spaces. In the remaining 319 data-sets, apparent diffusion coefficients (ADCs)
      values were calculated for all pixels exceeding a combined threshold in the
      diffusion-weighted data and in the non-diffusion-weighted data. The first part of
      the histogram represents pixels containing mostly brain tissue. The percentage of
      number of pixels in this part of the ADC histograms was evaluated for all
      patients and was correlated with the age of the patients. In all the areas
      examined, a monotone change of relative pixel numbers with the age of the
      patients was found. The reduction of the contribution of pixels containing mostly
      brain tissue accelerated with age and was found to be 0.18%/year in the age of
      20, 0.34%/year in the age of 50, and 0.50%/year in the age of 80. The observed
      decrease of the relative number of pixels from the brain tissue with increasing
      age corresponds to previously published results based on more time-consuming 3-D
      measurements. The presented technique uses a conventional clinical sequence and
      might be helpful in deciding whether an observed brain volume loss in a patient
      is within the normal range for the age of the patient. 

PMID- 24312051
TI  - Mismatch negativity (MMN) amplitude as a biomarker of sensory memory deficit in
      amnestic mild cognitive impairment.
AB  - It has been suggested that changes in some event-related potential (ERP)
      parameters associated with controlled processing of stimuli could be used as
      biomarkers of amnestic mild cognitive impairment (aMCI). However, data regarding
      the suitability of ERP components associated with automatic and involuntary
      processing of stimuli for this purpose are not conclusive. In the present study,
      we studied the Mismatch Negativity (MMN) component, a correlate of the automatic
      detection of changes in the acoustic environment, in healthy adults and adults
      with aMCI (age range: 50-87 years). An auditory-visual attention-distraction
      task, in two evaluations separated by an interval of between 18 and 24 months,
      was used. In both evaluations, the MMN amplitude was significantly smaller in the
      aMCI adults than in the control adults. In the first evaluation, such differences
      were observed for the subgroup of adults between 50 and 64 years of age, but not
      for the subgroup of 65 years and over. In the aMCI adults, the MMN amplitude was
      significantly smaller in the second evaluation than in the first evaluation, but
      no significant changes were observed in the control adult group. The MMN
      amplitude was found to be a sensitive and specific biomarker of aMCI, in both the
      first and second evaluation. 

PMID- 24312052
TI  - Attitudes of Hungarian asthmatic and COPD patients affecting disease control:
      empirical research based on Health Belief Model.
AB  - INTRODUCTION: Patient non-adherence to treatment is a major problem across most
      chronic diseases. In COPD and asthma treatments it is a complex issue because
      people need to make behavioral and lifestyle changes while taking medications.
      Poor adherence results in increased rates of morbidity and mortality, more
      frequent hospitalizations, and ultimately higher healthcare expenditures.
      MATERIALS AND METHODS: The objective of the study was to assess asthmatic and
      COPD patient's attitudes toward adherence in Hungary. Health Belief Model was
      used to help explain reasons of non-adherence. The results of the study should
      provide additional support to understanding health-related behaviors and to
      developing health related programs enhancing adherence of asthmatic and COPD
      patients. 145 diagnosed COPD patients and 161 diagnosed asthmatic patients were
      involved in 6 pulmonary centers. The questions were designed to measure Health
      Belief Model dimensions A 1-5 point verbal Likert scale was used. As a second
      stage, the answers were compared with the registered patient's personal health
      data available in pulmonary center's documentation. The data was analyzed using
      SPSS software. RESULTS: More than 32% of patients are very interested in new
      asthma or COPD research results, but their main information source is physician.
      The trust toward the physician is very high. Patients accept treatments and
      rarely ask questions. Respondents are cooperative but sometimes fail to follow
      therapeutic recommendations. There is no willingness to join self-help groups or
      associations. DISCUSSION: The paternalistic approach was generally accepted,
      moreover expected by the patients from the physicians. It is important to train
      patients, increase their self-efficacy, responsibility and involve them into self
      management programs. Both physicians and patients should be trained how to
      communicate-this approach can lead to increased understanding and better
      adherence.

PMID- 24312053
TI  - P-glycoprotein mediated efflux limits substrate and drug uptake in a preclinical
      brain metastases of breast cancer model.
AB  - The blood-brain barrier (BBB) is a specialized vascular interface that restricts
      the entry of many compounds into brain. This is accomplished through the sealing
      of vascular endothelial cells together with tight junction proteins to prevent
      paracellular diffusion. In addition, the BBB has a high degree of expression of
      numerous efflux transporters which actively extrude compounds back into blood.
      However, when a metastatic lesion develops in brain the vasculature is typically
      compromised with increases in passive permeability (blood-tumor barrier; BTB).
      What is not well documented is to what degree active efflux retains function at
      the BTB despite the changes observed in passive permeability. In addition, there
      have been previous reports documenting both increased and decreased expression of
      P-glycoprotein (P-gp) in lesion vasculature. Herein, we simultaneously administer
      a passive diffusion marker ((14)C-AIB) and a tracer subject to P-gp efflux
      (rhodamine 123) into a murine preclinical model of brain metastases of breast
      cancer. We observed that the metastatic lesions had similar expression (p > 0.05;
      n = 756-1214 vessels evaluated) at the BBB and the BTB. Moreover, tissue
      distribution of R123 was not significantly (p > 0.05) different between normal
      brain and the metastatic lesion. It is possible that the similar expression of P
      gp on the BBB and the BTB contribute to this phenomenon. Additionally we observed
      P-gp expression at the metastatic cancer cells adjacent to the vasculature which
      may also contribute to reduced R123 uptake into the lesion. The data suggest that
      despite the disrupted integrity of the BTB, efflux mechanisms appear to be
      intact, and may be functionally comparable to the normal BBB. The BTB is a
      significant hurdle to delivering drugs to brain metastasis. 

PMID- 24312054
TI  - ABCG2 is not able to catalyze glutathione efflux and does not contribute to GSH
      dependent collateral sensitivity.
AB  - ABCG2 is a key human ATP-binding cassette (ABC) transporter mediating cancer cell
      chemoresistance. In the case of ABCC1, another multidrug transporter, earlier
      findings documented that certain modulators greatly increase ABCC1-mediated
      glutathione (GSH) efflux and, upon depletion of intracellular GSH, induce
      "collateral sensitivity" leading to the apoptosis of multidrug resistant cells.
      Recently, it has been suggested that ABCG2 may mediate an active GSH transport.
      In order to explore if ABCG2-overexpressing cells may be similarly targeted, we
      first looked for the effects of ABCG2 expression on cellular GSH levels, and for
      an ABCG2-dependent GSH transport in HEK293 and MCF7 cells. We found that, while
      ABCG2 overexpression altered intracellular GSH levels in these transfected or
      drug-selected cells, ABCG2 inhibitors or transport modulators did not influence
      GSH efflux. We then performed direct measurements of drug-stimulated ATPase
      activity and (3)H-GSH transport in inside-out membrane vesicles of human ABC
      transporter-overexpressing Sf9 insect cells. Our results indicate that ABCG2
      ATPase is not modulated by GSH and, in contrast to ABCC1, ABCG2 does not catalyze
      any significant GSH transport. Our data suggest no direct interaction between the
      ABCG2 transporter and GSH, although a long-term modulation of cellular GSH by
      ABCG2 cannot be excluded. 

PMID- 24312055
TI  - Mind the gap! Connexins and pannexins in physiology, pharmacology and disease.

PMID- 24312056
TI  - Hypothesizing the body's genius to trigger and self-organize its healing: 25
      years using a standardized neurophysics therapy.
AB  - We aim for this contribution to operate bi-directionally, both as a "bedside to
      bench" reverse-translational fractal physiological hypothesis and as a
      methodological innovation to inform clinical practice. In 25 years using gym
      equipment therapeutically in non-research settings, the standardized therapy is
      consistently observed to trigger universal responses of micro to macro waves of
      system transition dynamics in the human nervous system. These are associated with
      observably desirable impacts on disorders, injuries, diseases, and athletic
      performance. Requisite conditions are therapeutic coaching, erect posture,
      extremely slow movements in mild resistance exercises, and executive control over
      arousal and attention. To motivate research into the physiological improvements
      and in validation studies, we integrate from across disciplines to hypothesize
      explanations for the relationships among the methods, the system dynamics, and
      evident results. Key hypotheses include: (1) Correctly-directed system efforts
      may reverse a system's heretofore misdirected efforts, restoring healthier
      neurophysiology. (2) The enhanced information processing accompanying good
      posture is an essential initial condition. (3) Behaviors accompanying exercises
      performed with few degrees of freedom amplify information processing, triggering
      destabilization and transition dynamics. (4) Executive control over arousal and
      attention is essential to release system constraints, amplifying and
      complexifying information. (5) The dynamics create necessary and in many cases
      evidently sufficient conditions for the body to resolve or improve its own
      conditions within often short time periods. Literature indicates how the human
      system possesses material self-awareness. A broad explanation for the nature and
      effects of the therapy appears rooted in the cascading recursions of the systems'
      dynamics, which appear to trigger health-fostering self-reorganizing processes
      when this therapy provides catalytic initial conditions. 

PMID- 24312057
TI  - Novel control of cardiac myofilament response to calcium by S-glutathionylation
      at specific sites of myosin binding protein C.
AB  - Our previous studies demonstrated a relation between glutathionylation of cardiac
      myosin binding protein C (cMyBP-C) and diastolic dysfunction in a hypertensive
      mouse model stressed by treatment with salt, deoxycorticosterone acetate, and
      unilateral nephrectomy. Although these results strongly indicated an important
      role for S-glutathionylation of myosin binding protein C as a modifier of
      myofilament function, indirect effects of other post-translational modifications
      may have occurred. Moreover, we did not determine the sites of thiol modification
      by glutathionylation. To address these issues, we developed an in vitro method to
      mimic the in situ S-glutathionylation of myofilament proteins and determined
      direct functional effects and sites of oxidative modification employing Western
      blotting and mass spectrometry. We induced glutathionylation in vitro by
      treatment of isolated myofibrils and detergent extracted fiber bundles (skinned
      fibers) with oxidized glutathione (GSSG). Immuno-blotting results revealed
      increased glutathionylation with GSSG treatment of a protein band around 140 kDa.
      Using tandem mass spectrometry, we identified the 140 kDa band as cMyBP-C and
      determined the sites of glutathionylation to be at cysteines 655, 479, and 627.
      Determination of the relation between Ca(2+)-activation of myofibrillar acto
      myosin ATPase rate demonstrated an increased Ca(2+)-sensitivity induced by the S
      glutathionylation. Force generating skinned fiber bundles also showed an increase
      in Ca-sensitivity when treated with oxidized glutathione, which was reversed with
      the reducing agent, dithiothreitol (DTT). Our data demonstrate that a specific
      and direct effect of S-glutathionylation of myosin binding protein C is a
      significant increase in myofilament Ca(2+)-sensitivity. Our data also provide new
      insights into the functional significance of oxidative modification of myosin
      binding protein C and the potential role of domains not previously considered to
      be functionally significant as controllers of myofilament Ca(2+)-responsiveness
      and dynamics. 

PMID- 24312058
TI  - A comparison between heart rate and heart rate variability as indicators of
      cardiac health and fitness.
AB  - Quantification of cardiac autonomic activity and control via heart rate (HR) and
      heart rate variability (HRV) is known to provide prognostic information in
      clinical populations. Issues with regard to standardization and interpretation of
      HRV data make the use of the more easily accessible HR on its own as an indicator
      of autonomic cardiac control very appealing. The aim of this study was to
      investigate the strength of associations between an important cardio vascular
      health metric such as VO2max and the following: HR, HRV indicators, and HR
      normalized HRV indicators. A cross sectional descriptive study was done including
      145 healthy volunteers aged between 18 and 22 years. HRV was quantified by time
      domain, frequency domain and Poincare plot analysis. Indirect VO2max was
      determined using the Multistage Coopers test. The Pearson correlation coefficient
      was calculated to quantify the strength of the associations. Both simple linear
      and multiple stepwise regressions were performed to be able to discriminate
      between the role of the individual indicators as well as their combined
      association with VO2max. Only HR, RR interval, and pNN50 showed significant (p <
      0.01, p < 0.01, and p = 0.03) correlations with VO2max. Stepwise multiple
      regression indicated that, when combining all HRV indicators the most important
      predictor of cardio vascular fitness as represented by VO2max, is HR. HR explains
      17% of the variation, while the inclusion of HF (high frequency HRV indicator)
      added only an additional 3.1% to the coefficient of determination. Results also
      showed when testing the normalized indicators, HR explained of the largest
      percentage of the changes in VO2max (16.5%). Thus, HR on its own is the most
      important predictor of changes in an important cardiac health metric such as
      VO2max. These results may indicate that during investigation of exercise ability
      (VO2max) phenomena, quantification of HRV may not add significant value. 

PMID- 24312059
TI  - On the use and misuse of externalist approaches in psychiatry.

PMID- 24312060
TI  - Toward a unifying taxonomy and definition for meditation.
AB  - One of the well-documented concerns confronting scholarly discourse about
      meditation is the plethora of semantic constructs and the lack of a unified
      definition and taxonomy. In recent years there have been several notable attempts
      to formulate new lexicons in order to define and categorize meditation methods.
      While these constructs have been useful and have encountered varying degrees of
      acceptance, they have also been subject to misinterpretation and debate, leaving
      the field devoid of a consensual paradigm. This paper attempts to influence this
      ongoing discussion by proposing two new models which hold the potential for
      enhanced scientific reliability and acceptance. Regarding the quest for a
      universally acceptable taxonomy, we suggest a paradigm shift away from the norm
      of fabricatIng new terminology from a first-person perspective. As an
      alternative, we propose a new taxonomic system based on the historically well
      established and commonly accepted third-person paradigm of Affect and Cognition,
      borrowed, in part, from the psychological and cognitive sciences. With regard to
      the elusive definitional problem, we propose a model of meditation which clearly
      distinguishes "method" from "state" and is conceptualized as a dynamic process
      which is inclusive of six related but distinct stages. The overall goal is to
      provide researchers with a reliable nomenclature with which to categorize and
      classify diverse meditation methods, and a conceptual framework which can provide
      direction for their research and a theoretical basis for their findings. 

PMID- 24312061
TI  - Self-organizing map models of language acquisition.
AB  - Connectionist models have had a profound impact on theories of language. While
      most early models were inspired by the classic parallel distributed processing
      architecture, recent models of language have explored various other types of
      models, including self-organizing models for language acquisition. In this paper,
      we aim at providing a review of the latter type of models, and highlight a number
      of simulation experiments that we have conducted based on these models. We show
      that self-organizing connectionist models can provide significant insights into
      long-standing debates in both monolingual and bilingual language development. We
      suggest future directions in which these models can be extended, to better
      connect with behavioral and neural data, and to make clear predictions in testing
      relevant psycholinguistic theories. 

PMID- 24312062
TI  - Commentary on Henrik Walter's "The third wave of biological psychiatry".

PMID- 24312063
TI  - Electrocortical activity associated with subjective communication with the
      deceased.
AB  - During advanced meditative practices, unusual perceptions can arise including the
      sense of receiving information about unknown people who are deceased. As with
      meditation, this mental state of communication with the deceased involves calming
      mental chatter and becoming receptive to subtle feelings and sensations.
      Psychometric and brain electrophysiology data were collected from six individuals
      who had previously reported accurate information about deceased individuals under
      double-blind conditions. Each experimental participant performed two tasks with
      eyes closed. In the first task, the participant was given only the first name of
      a deceased person and asked 25 questions. After each question, the participant
      was asked to silently perceive information relevant to the question for 20 s and
      then respond verbally. Responses were transcribed and then scored for accuracy by
      individuals who knew the deceased persons. Of the four mediums whose accuracy
      could be evaluated, three scored significantly above chance (p < 0.03). The
      correlation between accuracy and brain activity during the 20 s of silent
      mediumship communication was significant in frontal theta for one participant (p
      < 0.01). In the second task, participants were asked to experience four mental
      states for 1 min each: (1) thinking about a known living person, (2) listening to
      a biography, (3) thinking about an imaginary person, and (4) interacting mentally
      with a known deceased person. Each mental state was repeated three times.
      Statistically significant differences at p < 0.01 after correction for multiple
      comparisons in electrocortical activity among the four conditions were obtained
      in all six participants, primarily in the gamma band (which might be due to
      muscular activity). These differences suggest that the impression of
      communicating with the deceased may be a distinct mental state distinct from
      ordinary thinking or imagination. 

PMID- 24312065
TI  - The movements made by performers in a skilled quartet: a distinctive pattern, and
      the function that it serves.
AB  - When people perform a task as part of a joint action, their behavior is not the
      same as it would be if they were performing the same task alone, since it has to
      be adapted to facilitate shared understanding (or sometimes to prevent it). Joint
      performance of music offers a test bed for ecologically valid investigations of
      the way non-verbal behavior facilitates joint action. Here we compare the
      expressive movement of violinists when playing in solo and ensemble conditions.
      The first violinists of two string quartets (SQs), professional and student, were
      asked to play the same musical fragments in a solo condition and with the
      quartet. Synchronized multimodal recordings were created from the performances,
      using a specially developed software platform. Different patterns of head
      movement were observed. By quantifying them using an appropriate measure of
      entropy, we showed that head movements are more predictable in the quartet
      scenario. Rater evaluations showed that the change does not, as might be assumed,
      entail markedly reduced expression. They showed some ability to discriminate
      between solo and ensemble performances, but did not distinguish them in terms of
      emotional content or expressiveness. The data raise provocative questions about
      joint action in realistically complex scenarios. 

PMID- 24312064
TI  - Social orienting of children with autism to facial expressions and speech: a
      study with a wearable eye-tracker in naturalistic settings.
AB  - This study investigates attention orienting to social stimuli in children with
      Autism Spectrum Conditions (ASC) during dyadic social interactions taking place
      in real-life settings. We study the effect of social cues that differ in
      complexity and distinguish between social cues produced by facial expressions of
      emotion and those produced during speech. We record the children's gazes using a
      head-mounted eye-tracking device and report on a detailed and quantitative
      analysis of the motion of the gaze in response to the social cues. The study
      encompasses a group of children with ASC from 2 to 11-years old (n = 14) and a
      group of typically developing (TD) children (n = 17) between 3 and 6-years old.
      While the two groups orient overtly to facial expressions, children with ASC do
      so to a lesser extent. Children with ASC differ importantly from TD children in
      the way they respond to speech cues, displaying little overt shifting of
      attention to speaking faces. When children with ASC orient to facial expressions,
      they show reaction times and first fixation lengths similar to those presented by
      TD children. However, children with ASC orient to speaking faces slower than TD
      children. These results support the hypothesis that individuals affected by ASC
      have difficulties processing complex social sounds and detecting intermodal
      correspondence between facial and vocal information. It also corroborates
      evidence that people with ASC show reduced overt attention toward social stimuli.

PMID- 24312066
TI  - When co-action eliminates the Simon effect: disentangling the impact of co
      actor's presence and task sharing on joint-task performance.
AB  - This study aimed at assessing whether the mere belief of performing a task with
      another person, who is in charge of the complementary part of the task, is
      sufficient for the so-called joint Simon effect to occur. In all three
      experiments of the study, participants sat alone in a room and underwent two
      consecutive Go/NoGo tasks that were identical except for the instructions. In
      Experiment 1, participants performed the task first individually (baseline task),
      and then either co-acting with another person who responded from an unknown
      location to the NoGo stimuli (joint task) or imaging themselves responding to the
      NoGo stimuli (imaginative task). Relative to the baseline, the instructions of
      the imaginative task made the Simon effect occur, while those of the joint task
      were ineffective in eliciting the effect. This result suggests that sharing a
      task with a person who is known to be in charge of the complementary task, but is
      not physically present, is not sufficient to induce the representation of an
      alternative response able to produce interference, which happens instead when the
      instructions explicitly require to imagine such a response. Interestingly, we
      observed that when the Simon effect was already present in the baseline task
      (i.e., when the response alternative to the Go response was represented in the
      individual task due to non-social factors), it disappeared in the joint task. We
      propose that, when no information about the co-actor's position is available, the
      division of labor between the participant and co-actor allows participants to
      filter out the possible (incidental) representation of the alternative response
      from their task representation, thus eliminating potential sources of
      interference. This account is supported by the results of Experiments 2 and 3 and
      suggests that under certain circumstances task-sharing may reduce the
      interference produced by the irrelevant information, rather than increase it. 

PMID- 24312067
TI  - How are automatic processes elicited by intended actions?

PMID- 24312068
TI  - Context, cortex, and associations: a connectionist developmental approach to
      verbal analogies.
AB  - We present a PDP model of binary choice verbal analogy problems (A:B as
      C:[D1|D2], where D1 and D2 represent choice alternatives). We train a recurrent
      neural network in item-relation-item triples and use this network to test
      performance on analogy questions. Without training on analogy problems per se,
      the model explains the developmental shift from associative to relational
      responding as an emergent consequence of learning upon the environment's
      statistics. Such learning allows gradual, item-specific acquisition of relational
      knowledge to overcome the influence of unbalanced association frequency,
      accounting for association effects of analogical reasoning seen in cognitive
      development. The network also captures the overall degradation in performance
      after anterior temporal damage by deleting a fraction of learned connections,
      while capturing the return of associative dominance after frontal damage by
      treating frontal structures as necessary for maintaining activation of A and B
      while seeking a relation between C and D. While our theory is still far from
      being complete it provides a unified explanation of findings that need to be
      considered together in any integrated account of analogical reasoning. 

PMID- 24312069
TI  - Four decades of research on alexithymia: moving toward clinical applications.

PMID- 24312070
TI  - From weight loss to weight gain: appetite changes in major depressive disorder as
      a mirror into brain-environment interactions.

PMID- 24312071
TI  - Altered representation of facial expressions after early visual deprivation.
AB  - We investigated the effects of early visual deprivation on the underlying
      representation of the six basic emotions. Using multi-dimensional scaling (MDS),
      we compared the similarity judgments of adults who had missed early visual input
      because of bilateral congenital cataracts to control adults with normal vision.
      Participants made similarity judgments of the six basic emotional expressions,
      plus neutral, at three different intensities. Consistent with previous studies,
      the similarity judgments of typical adults could be modeled with four underlying
      dimensions, which can be interpreted as representing pleasure, arousal, potency
      and intensity of expressions. As a group, cataract-reversal patients showed a
      systematic structure with dimensions representing pleasure, potency, and
      intensity. However, an arousal dimension was not obvious in the patient group's
      judgments. Hierarchical clustering analysis revealed a pattern in patients seen
      in typical 7-year-olds but not typical 14-year-olds or adults. There was also
      more variability among the patients than among the controls, as evidenced by
      higher stress values for the MDS fit to the patients' data and more dispersed
      weightings on the four dimensions. The findings suggest an important role for
      early visual experience in shaping the later development of the representations
      of emotions. Since the normal underlying structure for emotion emerges
      postnatally and continues to be refined until late childhood, the altered
      representation of emotion in adult patients suggests a sleeper effect. 

PMID- 24312072
TI  - Statistical Issues in TBI Clinical Studies.
AB  - The identification and longitudinal assessment of traumatic brain injury presents
      several challenges. Because these injuries can have subtle effects, efforts to
      find quantitative physiological measures that can be used to characterize
      traumatic brain injury are receiving increased attention. The results of this
      research must be considered with care. Six reasons for cautious assessment are
      outlined in this paper. None of the issues raised here are new. They are standard
      elements in the technical literature that describes the mathematical analysis of
      clinical data. The purpose of this paper is to draw attention to these issues
      because they need to be considered when clinicians evaluate the usefulness of
      this research. In some instances these points are demonstrated by simulation
      studies of diagnostic processes. We take as an additional objective the explicit
      presentation of the mathematical methods used to reach these conclusions. This
      material is in the appendices. The following points are made: (1) A statistically
      significant separation of a clinical population from a control population does
      not ensure a successful diagnostic procedure. (2) Adding more variables to a
      diagnostic discrimination can, in some instances, actually reduce classification
      accuracy. (3) A high sensitivity and specificity in a TBI versus control
      population classification does not ensure diagnostic successes when the method is
      applied in a more general neuropsychiatric population. (4) Evaluation of
      treatment effectiveness must recognize that high variability is a pronounced
      characteristic of an injured central nervous system and that results can be
      confounded by either disease progression or spontaneous recovery. A large pre
      treatment versus post-treatment effect size does not, of itself, establish a
      successful treatment. (5) A procedure for discriminating between treatment
      responders and non-responders requires, minimally, a two phase investigation.
      This procedure must include a mechanism to discriminate between treatment
      responders, placebo responders, and spontaneous recovery. (6) A search for
      prodromes of neuropsychiatric disorders following traumatic brain injury can be
      implemented with these procedures. 

PMID- 24312073
TI  - Neurophysiology of robot-mediated training and therapy: a perspective for future
      use in clinical populations.
AB  - The recovery of functional movements following injury to the central nervous
      system (CNS) is multifaceted and is accompanied by processes occurring in the
      injured and non-injured hemispheres of the brain or above/below a spinal cord
      lesion. The changes in the CNS are the consequence of functional and structural
      processes collectively termed neuroplasticity and these may occur spontaneously
      and/or be induced by movement practice. The neurophysiological mechanisms
      underlying such brain plasticity may take different forms in different types of
      injury, for example stroke vs. spinal cord injury (SCI). Recovery of movement can
      be enhanced by intensive, repetitive, variable, and rewarding motor practice. To
      this end, robots that enable or facilitate repetitive movements have been
      developed to assist recovery and rehabilitation. Here, we suggest that some
      elements of robot-mediated training such as assistance and perturbation may have
      the potential to enhance neuroplasticity. Together the elemental components for
      developing integrated robot-mediated training protocols may form part of a
      neurorehabilitation framework alongside those methods already employed by
      therapists. Robots could thus open up a wider choice of options for delivering
      movement rehabilitation grounded on the principles underpinning neuroplasticity
      in the human CNS. 

PMID- 24312075
TI  - Long-term viral brain-derived neurotrophic factor delivery promotes spasticity in
      rats with a cervical spinal cord hemisection.
AB  - We have recently reported that rats with complete thoracic spinal cord injury
      (SCI) that received a combinatorial treatment, including viral brain-derived
      neurotrophic factor (BDNF) delivery in the spinal cord, not only showed enhanced
      axonal regeneration, but also deterioration of hind-limb motor function. By
      demonstrating that BDNF over-expression can trigger spasticity-like symptoms in a
      rat model of sacral SCI, we proposed a causal relationship between the observed
      spasticity-like symptoms (i.e., resistance to passive range of motion) and the
      over-expression of BDNF. The current study was originally designed to evaluate a
      comparable combined treatment for cervical SCI in the rat to improve motor
      recovery. Once again we found similar signs of spasticity involving clenching of
      the paws and wrist flexion. This finding changed the focus of the study and, we
      then explored whether this spasticity-like symptom is directly related to the
      over-expression of BDNF by administering a BDNF antagonist. Using
      electromyographic measurements we showed that this treatment gradually diminished
      the resistance to overcome forelimb flexion in an acute experiment. Thus, we
      conclude that neuro-excitatory effects of chronic BDNF delivery together with
      diminished descending control after SCI can result in adverse effects. 

PMID- 24312074
TI  - Assessing neuro-systemic & behavioral components in the pathophysiology of blast
      related brain injury.
AB  - Among the U.S. military personnel, blast injury is among the leading causes of
      brain injury. During the past decade, it has become apparent that even blast
      injury as a form of mild traumatic brain injury (mTBI) may lead to multiple
      different adverse outcomes, such as neuropsychiatric symptoms and long-term
      cognitive disability. Blast injury is characterized by blast overpressure, blast
      duration, and blast impulse. While the blast injuries of a victim close to the
      explosion will be severe, majority of victims are usually at a distance leading
      to milder form described as mild blast TBI (mbTBI). A major feature of mbTBI is
      its complex manifestation occurring in concert at different organ levels
      involving systemic, cerebral, neuronal, and neuropsychiatric responses; some of
      which are shared with other forms of brain trauma such as acute brain injury and
      other neuropsychiatric disorders such as post-traumatic stress disorder. The
      pathophysiology of blast injury exposure involves complex cascades of chronic
      psychological stress, autonomic dysfunction, and neuro/systemic inflammation.
      These factors render blast injury as an arduous challenge in terms of diagnosis
      and treatment as well as identification of sensitive and specific biomarkers
      distinguishing mTBI from other non-TBI pathologies and from neuropsychiatric
      disorders with similar symptoms. This is due to the "distinct" but shared and
      partially identified biochemical pathways and neuro-histopathological changes
      that might be linked to behavioral deficits observed. Taken together, this
      article aims to provide an overview of the current status of the cellular and
      pathological mechanisms involved in blast overpressure injury and argues for the
      urgent need to identify potential biomarkers that can hint at the different
      mechanisms involved. 

PMID- 24312076
TI  - Combination of PET and Magnetoencephalography in the Presurgical Assessment of
      MRI-Negative Epilepsy.
AB  - Despite major advances in neuroimaging, no lesion is visualized on MRI in up to a
      quarter of patients with drug-resistant focal epilepsy presenting for presurgical
      evaluation. These patients demonstrate poorer surgical outcomes than those with
      lesion seen on MRI. Accurate localization of the seizure onset zone (SOZ) is more
      difficult in MRI-negative patients and often requires invasive EEG recordings.
      Positron emission tomography (PET) and magnetoencephalography (MEG) have been
      proposed as clinically relevant tools to localize the SOZ prior to intracranial
      EEG recordings. However, there is no consensus regarding the optimal gold
      standard that should be used for assessing the performance of these presurgical
      investigations. Here, we review the current knowledge concerning the usefulness
      of PET and MEG for presurgical assessment of MRI-negative epilepsy. Beyond the
      individual diagnostic performance of MEG and of different PET tracers, including
      [(18)F]-fluorodeoxyglucose, [(11)C]flumazenil, and markers of 5-HT1A receptors,
      recent data suggest that the combination of PET and MEG might provide greater
      sensitivity and specificity than that of each of the two individual tests in
      patients with normal MRI. 

PMID- 24312077
TI  - Role of Direct vs. Indirect Pathways from the Motor Cortex to Spinal Motoneurons
      in the Control of Hand Dexterity.
AB  - Evolutionally, development of the direct connection from the motor cortex to
      spinal motoneurons [corticomotoneuronal (CM) pathway] parallels the ability of
      hand dexterity. Damage to the corticofugal fibers in higher primates resulted in
      deficit of fractionated digit movements. Based on such observations, it was
      generally believed that the CM pathway plays a critical role in the control of
      hand dexterity. On the other hand, a number of "phylogenetically older" indirect
      pathways from the motor cortex to motoneurons still exist in primates. The
      indirect pathways are mediated by intercalated neurons such as segmental
      interneurons (sINs), propriospinal neurons (PNs) reticulospinal neurons (RSNs),
      or rubrospinal neurons (RuSNs). However, their contribution to hand dexterity
      remains elusive. Lesion of the brainstem pyramid sparing the transmission through
      the RuSNs and RSNs, resulted in permanent deficit of fractionated digit movements
      in macaque monkeys. On the other hand, in our recent study, after lesion of the
      dorsolateral funiculus (DLF) at the C5 segment, which removed the lateral
      corticospinal tract (l-CST) including the CM pathway and the transmission through
      sINs and RuSNs but spared the processing through the PNs and RSNs, fractionated
      digit movements recovered within several weeks. These results suggest that the
      PNs can be involved in the recovery of fractionated digit movements, but the RSNs
      and RuSNs have less capacity in this regard. However, on closer inspection, it
      was found that the activation pattern of hand and arm muscles considerably
      changed after the C5 lesion, suggesting limitation of PNs for the compensation of
      hand dexterity. Altogether, it is suggested that PNs, RSNs RuSNs, and the CM
      pathway (plus sINs) make a different contribution to the hand dexterity and
      appearance of motor deficit of the hand dexterity caused by damage to the
      corticofugal fibers and potential of recovery varies depending on the
      rostrocaudal level of the lesion. 

PMID- 24312078
TI  - Thyroid function in male infertility.

PMID- 24312081
TI  - Migration of rice planthoppers and their vectored re-emerging and novel rice
      viruses in East Asia.
AB  - This review examines recent studies of the migration of three rice planthoppers,
      Laodelphax striatellus, Sogatella furcifera, and Nilaparvata lugens, in East
      Asia. Laodelphax striatellus has recently broken out in Jiangsu province, eastern
      China. The population density in the province started to increase in the early
      2000s and peaked in 2004. In 2005, Rice stripe virus (RSV) viruliferous rate of
      L. striatellus peaked at 31.3%. Since then, rice stripe disease spread severely
      across the whole province. Due to the migration of the RSV vectors, the rice
      stripe disease spread to neighboring countries Japan and Korea. An overseas
      migration of L. striatellus that occurred in 2008 was analyzed, when a slow
      moving cold vortex, a type of low pressure system, reached western Japan from
      Jiangsu, carrying the insects into Japan. Subsequently the rice stripe diseases
      struck these areas in Japan severely. In Korea, similar situations occurred in
      2009, 2011, and 2012. Their migration sources were also estimated to be in
      Jiangsu by backward trajectory analysis. Rice black-streaked dwarf virus, whose
      vector is L. striatellus, has recently re-emerged in eastern China, and the
      evidence for overseas migrations of the virus, just like the RSV's migrations,
      has been given. A method of predicting the overseas migration of L. striatellus
      has been developed by Japanese, Chinese, and Korean institutes. An evaluation of
      the prediction showed that this method properly predicted migration events that
      occurred in East Asia from 2008 to 2011. Southern rice black-streaked dwarf virus
      (SRBSDV) was first found in Guangdong province. Its vector is S. furcifera. An
      outbreak of SRBSDV occurred in southern China in 2009 and spread to Vietnam the
      same year. This disease and virus were also found in Japan in 2010. The epidemic
      triggered many migration studies to investigate concrete spring-summer migration
      routes in China, and the addition of migration sources for early arrivals in
      Guangdong and Guangxi have been proposed. Nilaparvata lugens is also an important
      insect pest of rice. Its migration situations on the Indochina peninsula and
      return migrations in China are discussed. 

PMID- 24312079
TI  - Neurobiological study of fish brains gives insights into the nature of
      gonadotropin-releasing hormone 1-3 neurons.
AB  - Accumulating evidence suggests that up to three different molecular species of
      GnRH peptides encoded by different paralogs of gnrh genes are expressed by
      anatomically distinct groups of GnRH neurons in the brain of one vertebrate
      species. They are called gnrh1, gnrh2, and gnrh3. Recent evidence from molecular,
      anatomical, and physiological experiments strongly suggests that each GnRH system
      functions differently. Here, we review recent advancement in the functional
      studies of the three different GnRH neuron systems, mainly focusing on the
      electrophysiological analysis of the GnRH-green fluorescent protein (GFP)
      transgenic animals. The introduction of GFP-transgenic animals for the
      electrophysiological analysis of GnRH neurons greatly advanced our knowledge on
      their anatomy and electrophysiology, especially of gnrh1 neurons, which has long
      defied detailed electrophysiological analysis of single neurons because of their
      small size and scattered distribution. Based on the results of recent studies, we
      propose that different electrophysiological properties, especially the
      spontaneous patterns of electrical activities and their time-dependent changes,
      and the axonal projections characterize the different functions of GnRH1-3
      neurons; GnRH1 neurons act as hypophysiotropic neuroendocrine regulators, and
      GnRH2 and GnRH3 neurons act as neuromodulators in wide areas of the brain. 

PMID- 24312082
TI  - The epsomitic phototrophic microbial mat of Hot Lake, Washington: community
      structural responses to seasonal cycling.
AB  - Phototrophic microbial mats are compact ecosystems composed of highly interactive
      organisms in which energy and element cycling take place over millimeter-to
      centimeter-scale distances. Although microbial mats are common in hypersaline
      environments, they have not been extensively characterized in systems dominated
      by divalent ions. Hot Lake is a meromictic, epsomitic lake that occupies a small,
      endorheic basin in north-central Washington. The lake harbors a benthic,
      phototrophic mat that assembles each spring, disassembles each fall, and is
      subject to greater than tenfold variation in salinity (primarily Mg(2+) and SO(2
      ) 4) and irradiation over the annual cycle. We examined spatiotemporal variation
      in the mat community at five time points throughout the annual cycle with respect
      to prevailing physicochemical parameters by amplicon sequencing of the V4 region
      of the 16S rRNA gene coupled to near-full-length 16S RNA clone sequences. The
      composition of these microbial communities was relatively stable over the
      seasonal cycle and included dominant populations of Cyanobacteria, primarily a
      group IV cyanobacterium (Leptolyngbya), and Alphaproteobacteria (specifically,
      members of Rhodobacteraceae and Geminicoccus). Members of Gammaproteobacteria
      (e.g., Thioalkalivibrio and Halochromatium) and Deltaproteobacteria (e.g.,
      Desulfofustis) that are likely to be involved in sulfur cycling peaked in summer
      and declined significantly by mid-fall, mirroring larger trends in mat community
      richness and evenness. Phylogenetic turnover analysis of abundant phylotypes
      employing environmental metadata suggests that seasonal shifts in light
      variability exert a dominant influence on the composition of Hot Lake microbial
      mat communities. The seasonal development and organization of these structured
      microbial mats provide opportunities for analysis of the temporal and physical
      dynamics that feed back to community function. 

PMID- 24312083
TI  - Purification, biochemical characterization and self-assembled structure of a
      fengycin-like antifungal peptide from Bacillus thuringiensis strain SM1.
AB  - An antifungal lipopeptide fengycin, producing strain SM1 was isolated from farm
      land soil sample and identified as Bacillus thuringiensis strain SM1 by using 16S
      rDNA analysis. Fengycin detected in the culture extract was further purified
      using HPLC and showed a molecular mass of 1492.8 Da by MALDI-TOF-MS analysis.
      Purified fengycin was allowed to construct their self-assembled structure onto a
      hydrophobic surface showing a clear improvement of antibacterial activity. In
      self-assembly, fengycin adapts a spherical micelle core shell like structure.
      Self-assembled fengycin may be a successful antimicrobial compound modifying its
      action from confined antifungal function. Besides it can open up a new area of
      research in supramolecular lipopeptide based compound making. This can revealed
      the mode of action of this unique self-assembled structure to fully evaluate its
      potential for use as an antimicrobial drug to control the emergence of bacterial
      infection. 

PMID- 24312084
TI  - A mini review on aflatoxin exposure in Malaysia: past, present and future.
AB  - This mini review article described the exposure of aflatoxin in Malaysia,
      including its presence in the foodstuffs and the detection of aflatoxin
      biomarkers in human biological samples. Historically, the exposure of aflatoxin
      in Malaysia can be dated in 1960s where an outbreak of disease in pig farms
      caused severe liver damage to the animals. Later, an aflatoxicosis case in Perak
      in 1988 was reported and caused death to 13 children, as up to 3 mg of aflatoxin
      was present in a single serving of contaminated noodles. Since then, extensive
      research on aflatoxin has been conducted in Malaysia. The food commodities such
      as peanuts, cereals, spices, and their products are the main commodities commonly
      found to be contaminated with aflatoxin. Surprisingly, some of the contaminated
      foods had levels greater than the permissible limit adopted by the Malaysian Food
      Regulation 1985. Besides, exposure assessment through the measurement of
      aflatoxin biomarkers in human biological samples is still in its infancy stage.
      Nevertheless, some studies had reported the presence of these biomarkers. In
      fact, it is postulated that Malaysians are moderately exposed to aflatoxin
      compared to those high risk populations, where aflatoxin contamination in the
      diets is prevalent. Since the ingestion of aflatoxin could be the integral to the
      development of liver cancer, the incidence of cancer attributable by dietary
      aflatoxin exposure in Malaysia has also been reported and published in the
      literatures. Regardless of these findings, the more important task is to monitor
      and control humans from being exposed to aflatoxin. The enforcement of law is
      insufficient to minimize human exposure to aflatoxin. Preventive strategies
      include agricultural, dietary, and clinical measures should be implemented. With
      the current research on aflatoxin in Malaysia, a global networking for research
      collaboration is needed to expand the knowledge and disseminate the information
      to the global scientific community. 

PMID- 24312080
TI  - Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating
      cyclic nucleotides into the network.
AB  - Gonadotropin-releasing hormone (GnRH) is the primary regulator of mammalian
      reproductive function in both males and females. It acts via G-protein coupled
      receptors on gonadotropes to stimulate synthesis and secretion of the
      gonadotropin hormones luteinizing hormone and follicle-stimulating hormone. These
      receptors couple primarily via G-proteins of the Gq/ll family, driving activation
      of phospholipases C and mediating GnRH effects on gonadotropin synthesis and
      secretion. There is also good evidence that GnRH causes activation of other
      heterotrimeric G-proteins (Gs and Gi) with consequent effects on cyclic AMP
      production, as well as for effects on the soluble and particulate guanylyl
      cyclases that generate cGMP. Here we provide an overview of these pathways. We
      emphasize mechanisms underpinning pulsatile hormone signaling and the possible
      interplay of GnRH and autocrine or paracrine regulatory mechanisms in control of
      cyclic nucleotide signaling. 

PMID- 24312086
TI  - Microbial enzymes that oxidize hydrocarbons.

PMID- 24312085
TI  - Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick
      countermeasures, and a suitable environment for pathogen establishment.
AB  - Ticks are unique among hematophagous arthropods by continuous attachment to host
      skin and blood feeding for days; complexity and diversity of biologically active
      molecules differentially expressed in saliva of tick species; their ability to
      modulate the host defenses of pain and itch, hemostasis, inflammation, innate and
      adaptive immunity, and wound healing; and, the diverse array of infectious agents
      they transmit. All of these interactions occur at the cutaneous interface in a
      complex sequence of carefully choreographed host defense responses and tick
      countermeasures resulting in an environment that facilitates successful blood
      feeding and establishment of tick-borne infectious agents within the host. Here,
      we examine diverse patterns of tick attachment to host skin, blood feeding
      mechanisms, salivary gland transcriptomes, bioactive molecules in tick saliva,
      timing of pathogen transmission, and host responses to tick bite. Ticks engage
      and modulate cutaneous and systemic immune defenses involving keratinocytes,
      natural killer cells, dendritic cells, T cell subpopulations (Th1, Th2, Th17,
      Treg), B cells, neutrophils, mast cells, basophils, endothelial cells, cytokines,
      chemokines, complement, and extracellular matrix. A framework is proposed that
      integrates tick induced changes of skin immune effectors with their ability to
      respond to tick-borne pathogens. Implications of these changes are addressed.
      What are the consequences of tick modulation of host cutaneous defenses? Does
      diversity of salivary gland transcriptomes determine differential modulation of
      host inflammation and immune defenses and therefore, in part, the clades of
      pathogens effectively transmitted by different tick species? Do ticks create an
      immunologically modified cutaneous environment that enhances specific pathogen
      establishment? Can tick saliva molecules be used to develop vaccines that block
      pathogen transmission? 

PMID- 24312088
TI  - Changes in community composition of ammonia-oxidizing betaproteobacteria from
      stands of Black mangrove (Avicennia germinans) in response to ammonia enrichment
      and more oxic conditions.
AB  - In flooded and non-flooded impounded forests of Black mangrove (Avicennia
      germinans), the community structure of the ammonia-oxidizing betaproteobacteria
      (beta-AOB) differed among distinct mangrove vegetation cover types and
      hydrological regimes. This had been explained by a differential response of
      lineages of beta-AOB to the prevailing soil conditions that included increased
      levels of moisture and ammonium. To test this hypothesis, slurries of soils
      collected from a flooded and a non-flooded impoundment were subjected to enhanced
      levels of ammonium in the absence and presence of additional shaking. After a
      period of 6 days, the community composition of the beta-AOB based on the 16S rRNA
      gene was determined and compared with the original community structures.
      Regardless of the incubation conditions and the origin of the samples, sequences
      belonging to the Nitrosomonas aestuarii lineage became increasingly dominant,
      whereas the number of sequences of the lineages of Nitrosospira (i.e., Cluster 1)
      and Nitrosomonas sp. Nm143 declined. Changes in community structure were related
      to changes in community sizes determined by quantitative PCR based on the amoA
      gene. The amoA gene copy numbers of beta-AOB were compared to those of the
      ammonia-oxidizing archaea (AOA). Gene copy numbers of the bacteria increased
      irrespective of incubation conditions, but the numbers of archaea declined in the
      continuously shaken cultures. This observation is discussed in relation to the
      distribution of the beta-AOB lineages in the impounded Black mangrove forests. 

PMID- 24312087
TI  - Diversity of reductive dehalogenase genes from environmental samples and
      enrichment cultures identified with degenerate primer PCR screens.
AB  - Reductive dehalogenases are the critical enzymes for anaerobic organohalide
      respiration, a microbial metabolic process that has been harnessed for
      bioremediation efforts to resolve chlorinated solvent contamination in
      groundwater and is implicated in the global halogen cycle. Reductive dehalogenase
      sequence diversity is informative for the dechlorination potential of the site or
      enrichment culture. A suite of degenerate PCR primers targeting a comprehensive
      curated set of reductive dehalogenase genes was designed and applied to 12 DNA
      samples extracted from contaminated and pristine sites, as well as six enrichment
      cultures capable of reducing chlorinated compounds to non-toxic end-products. The
      amplified gene products from four environmental sites and two enrichment cultures
      were sequenced using Illumina HiSeq, and the reductive dehalogenase complement of
      each sample determined. The results indicate that the diversity of the reductive
      dehalogenase gene family is much deeper than is currently accounted for: one
      third of the translated proteins have less than 70% pairwise amino acid identity
      to database sequences. Approximately 60% of the sequenced reductive dehalogenase
      genes were broadly distributed, being identified in four or more samples, and
      often in previously sequenced genomes as well. In contrast, 17% of the sequenced
      reductive dehalogenases were unique, present in only a single sample and bearing
      less than 90% pairwise amino acid identity to any previously identified proteins.
      Many of the broadly distributed reductive dehalogenases are uncharacterized in
      terms of their substrate specificity, making these intriguing targets for further
      biochemical experimentation. Finally, comparison of samples from a contaminated
      site and an enrichment culture derived from the same site 8 years prior allowed
      examination of the effect of the enrichment process. 

PMID- 24312089
TI  - In silico analysis of bacterial arsenic islands reveals remarkable synteny and
      functional relatedness between arsenate and phosphate.
AB  - In order to construct a more universal model for understanding the genetic
      requirements for bacterial AsIII oxidation, an in silico examination of the
      available sequences in the GenBank was assessed and revealed 21 conserved 5-71 kb
      arsenic islands within phylogenetically diverse bacterial genomes. The arsenic
      islands included the AsIII oxidase structural genes aioBA, ars operons (e.g.,
      arsRCB) which code for arsenic resistance, and pho, pst, and phn genes known to
      be part of the classical phosphate stress response and that encode functions
      associated with regulating and acquiring organic and inorganic phosphorus. The
      regulatory genes aioXSR were also an island component, but only in Proteobacteria
      and orientated differently depending on whether they were in alpha-Proteobacteria
      or beta-/gamma-Proteobacteria. Curiously though, while these regulatory genes
      have been shown to be essential to AsIII oxidation in the Proteobacteria, they
      are absent in most other organisms examined, inferring different regulatory
      mechanism(s) yet to be discovered. Phylogenetic analysis of the aio, ars, pst,
      and phn genes revealed evidence of both vertical inheritance and horizontal gene
      transfer (HGT). It is therefore likely the arsenic islands did not evolve as a
      whole unit but formed independently by acquisition of functionally related genes
      and operons in respective strains. Considering gene synteny and structural
      analogies between arsenate and phosphate, we presumed that these genes function
      together in helping these microbes to be able to use even low concentrations of
      phosphorus needed for vital functions under high concentrations of arsenic, and
      defined these sequences as the arsenic islands. 

PMID- 24312090
TI  - Novel plant inputs influencing Ralstonia solanacearum during infection.
AB  - Ralstonia solanacearum is a soil and water-borne pathogen that can infect a wide
      range of plants and cause the devastating bacterial wilt disease. To successfully
      colonize a host, R. solanacearum requires the type III secretion system (T3SS),
      which delivers bacterial effector proteins inside the plant cells. HrpG is a
      central transcriptional regulator that drives the expression of the T3SS and
      other virulence determinants. hrpG transcription is highly induced upon plant
      cell contact and its product is also post-transcriptionally activated by
      metabolic signals present when bacteria are grown in minimal medium (MM). Here,
      we describe a transcriptional induction of hrpG at early stages of bacterial co
      culture with plant cells that caused overexpression of the downstream T3SS
      effector genes. This induction was maintained in a strain devoid of prhA, the
      outer membrane receptor that senses bacterial contact with plant cells,
      demonstrating that this is a response to an unknown signal. Induction was
      unaffected after disruption of the known R. solanacearum pathogenicity
      regulators, indicating that it is controlled by a non-described system. Moreover,
      plant contact-independent signals are also important in planta, as shown by the
      hrpG induction triggered by apoplastic and xylem extracts. We also found that
      none of the amino acids or sugars present in the apoplast and xylem saps studied
      correlated with hrpG induction. This suggests that a small molecule or an
      environmental condition is responsible for the T3SS gene expression inside the
      plants. Our results also highlight the abundance and diversity of possible
      carbon, nitrogen and energy sources likely used by R. solanacearum during growth
      in planta. 

PMID- 24312091
TI  - IgA B Cell Responses to Gut Mucosal Antigens: Do We Know it all?

PMID- 24312092
TI  - Regulation of MHC Class II-Peptide Complex Expression by Ubiquitination.
AB  - MHC class II (MHC-II) molecules are present on antigen presenting cells (APCs)
      and these molecules function by binding antigenic peptides and presenting these
      peptides to antigen-specific CD4(+) T cells. APCs continuously generate and
      degrade MHC-II molecules, and ubiquitination of MHC-II has recently been shown to
      be a key regulator of MHC-II expression in dendritic cells (DCs). In this mini
      review we will examine the mechanism by which the E3 ubiquitin ligase March-I
      regulates MHC-II expression on APCs and will discuss the functional consequences
      of altering MHC-II ubiquitination. 

PMID- 24312093
TI  - Sand-fly saliva-leishmania-man: the trigger trio.
AB  - Leishmaniases are worldwide diseases transmitted to the vertebrate host by the
      bite of an infected sand-fly. Sand-fly biting and parasite inoculation are
      accompanied by the injection of salivary molecules, whose immunomodulatory
      properties are actively being studied. This mini review focuses on how the
      interactions between sand-fly saliva and the immune system may shape the outcome
      of infection, given its immunomodulatory properties, in experimental models and
      in the endemic area. Additionally, we approach the recent contributions regarding
      the identification of individual salivary components and how these are currently
      being considered as additional components of a vaccine against leishmaniasis. 

PMID- 24312094
TI  - CD4(+) T Cell-Receptor Repertoire Diversity is Compromised in the Spleen but Not
      in the Bone Marrow of Aged Mice Due to Private and Sporadic Clonal Expansions.
AB  - Reduction in T cell receptor (TCR) diversity in old age is considered as a major
      cause for immune complications in the elderly population. Here, we explored the
      consequences of aging on the TCR repertoire in mice using high-throughput
      sequencing (TCR-seq). We mapped the TCRbeta repertoire of CD4+ T cells isolated
      from bone marrow (BM) and spleen of young and old mice. We found that TCRbeta
      diversity is reduced in spleens of aged mice but not in their BM. Splenic CD4+ T
      cells were also skewed toward an effector memory phenotype in old mice, while BM
      cells preserved their memory phenotype with age. Analysis of Vbeta and Jbeta gene
      usage across samples, as well as comparison of CDR3 length distributions, showed
      no significant age dependent changes. However, comparison of the frequencies of
      amino-acid (AA) TCRbeta sequences between samples revealed repertoire changes
      that occurred at a more refined scale. The BM-derived TCRbeta repertoire was
      found to be similar among individual mice regardless of their age. In contrast,
      the splenic repertoire of old mice was not similar to those of young mice, but
      showed an increased similarity with the BM repertoire. Each old-mouse had a
      private set of expanded TCRbeta sequences. Interestingly, a fraction of these
      sequences was found also in the BM of the same individual, sharing the same
      nucleotide sequence. Together, these findings show that the composition and
      phenotype of the CD4+ T cell BM repertoire are relatively stable with age, while
      diversity of the splenic repertoire is severely reduced. This reduction is caused
      by idiosyncratic expansions of tens to hundreds of T cell clonotypes, which
      dominate the repertoire of each individual. We suggest that these private and
      abundant clonotypes are generated by sporadic clonal expansions, some of which
      correspond to pre-existing BM clonotypes. These organ- and age-specific changes
      of the TCRbeta repertoire have implications for understanding and manipulating
      age-associated immune decline. 

PMID- 24312096
TI  - A Novel Method Linking Antigen Presentation by Human Monocyte-Derived Macrophages
      to CD8(+) T Cell Polyfunctionality.
AB  - To understand the interactions between innate and adaptive immunity, and
      specifically how virally infected macrophages impact T cell function, novel
      assays examining the ability of macrophages to present antigen to CD8(+) T cells
      are needed. In the present study, we have developed a robust in vitro assay to
      measure how antigen presentation by human monocyte-derived macrophages (MDMs)
      affects the functional capacity of autologous CD8(+) T cells. The assay is based
      on the polyfunctional characteristics of antigen-specific CD8(+) T cells, and is
      thus called a Mac-CD8 Polyfunctionality Assay. Following purification of
      monocytes and their maturation to MDMs, MDMs were pulsed with an antigenic
      peptide to be presented to CD8(+) T cells. Peptide-pulsed MDMs were then
      incubated with antigen-specific CD8(+) T cells in order to assess the efficacy of
      antigen presentation to T cells. CD8(+) T cell polyfunctionality was assessed by
      staining with mAbs to IFN-gamma, TNF-alpha, and CD107a in a multi-color
      intracellular cytokine staining assay. To highlight the utility of the Mac-CD8
      Polyfunctionality Assay, we assessed the effects of influenza infection on the
      ability of human macrophages to present antigen to CD8(+) T cells. We found that
      influenza infection of human MDMs can alter the effector efficacy of MDMs to
      activate more CD8(+) T cells with cytotoxic capacity. This has important
      implications for understanding how the virus-infected macrophages affect adaptive
      immunity at the site of infection. 

PMID- 24312095
TI  - Human immunodeficiency virus and heparan sulfate: from attachment to entry
      inhibition.
AB  - By targeting cells that provide protection against infection, HIV-1 causes
      acquired immunodeficiency syndrome. Infection starts when gp120, the viral
      envelope glycoprotein, binds to CD4 and to a chemokine receptor usually CCR5 or
      CXCR4. As many microorganisms, HIV-1 also interacts with heparan sulfate (HS), a
      complex group of cell surface associated anionic polysaccharides. It has been
      thought that this binding, occurring at a step prior to CD4 recognition,
      increases infectivity by pre-concentrating the virion particles at the cell
      surface. Early work, dating from before the identification of CCR5 and CXCR4,
      showed that a variety of HS mimetics bind to the gp120 V3 loop through
      electrostatic interactions, compete with cell surface associated HS to bind the
      virus and consequently, neutralize the infectivity of a number of T-cell line
      adapted HIV-1 strains. However, progress made to better understand HIV-1
      attachment and entry, coupled with the recent identification of additional gp120
      regions mediating HS recognition, have considerably modified this view. Firstly,
      the V3 loop from CXCR4-using viruses is much more positively charged compared to
      those using CCR5. HS inhibition of cell attachment is thus restricted to CXCR4
      using viruses (such as T-cell line-adapted HIV-1). Secondly, studies aiming at
      characterizing the gp120/HS complex revealed that HS binding was far more complex
      than previously thought: in addition to the V3 loop of CXCR4 tropic gp120, HS
      interacts with several other cryptic areas of the protein, which can be induced
      upon CD4 binding, and are conserved amongst CCR5 and CXCR4 viruses. In view of
      these data, this review will detail the present knowledge on HS binding to HIV-1,
      with regards to attachment and entry processes. It will discuss the perspective
      of targeting the gp120 co-receptor binding site with HS mimetic compounds, a
      strategy that recently gave rise to entry inhibitors that work in the low
      nanomolar range, independently of co-receptor usage. 

PMID- 24312097
TI  - Activation of Lymphocyte Cytolytic Machinery: Where are We?
AB  - Target cell recognition by cytotoxic lymphocytes implies the simultaneous
      engagement and clustering of adhesion and activating receptors followed by the
      activation of an array of signal transduction pathways. The cytotoxic immune
      synapse represents the highly specialized dynamic interface formed between the
      cytolytic effector and its target that allows temporal and spatial integration of
      signals responsible for a defined sequence of processes culminating with the
      polarized secretion of lytic granules. Over the last decades, much attention has
      been given to the molecular signals coupling receptor ligation to the activation
      of cytolytic machinery. Moreover, in the last 10 years the discovery of genetic
      defects affecting cytotoxic responses greatly boosted our knowledge on the
      molecular effectors involved in the regulation of discrete phases of cytotoxic
      process at post-receptor levels. More recently, the use of super resolution and
      total internal reflection fluorescence imaging technologies added new insights on
      the dynamic reorganization of receptor and signaling molecules at lytic synapse
      as well as on the relationship between granule dynamics and cytoskeleton
      remodeling. To date we have a solid knowledge of the molecular mechanisms
      governing granule movement and secretion, being not yet fully unraveled the
      machinery that couples early receptor signaling to the late stage of synapse
      remodeling and granule dynamics. Here we highlight recent advances in our
      understanding of the molecular mechanisms acting in the activation of cytolytic
      machinery, also discussing similarities and differences between Natural killer
      cells and cytotoxic CD8(+) T cells. 

PMID- 24312098
TI  - The Interleukin-1alpha Precursor is Biologically Active and is Likely a Key
      Alarmin in the IL-1 Family of Cytokines.
AB  - Among the 11 members of the IL-1 family cytokines, the precursors of IL-1alpha,
      IL-1beta, and IL-33 have relatively long N-terminal pro-sequences of
      approximately 100 amino acid residues prior to the N-terminus of the mature
      forms. Compared to the mature forms secreted from the cell, 80-90% of the primary
      translation product is in the intracellular compartment in the precursor form.
      However, the precursors are readily released from cells during infections but
      also with non-infectious conditions such a hypoxia and trauma. In this setting,
      the precursors act rapidly as "alarmins" in the absence of a processing mechanism
      to remove the pro-sequence and generate a mature form. In the case of IL-1alpha,
      the release of the precursor activates adjacent cells via receptor-mediated
      signaling. However, there are no data comparing the specific activity of the IL
      1alpha precursor to the mature form. In the present study, we compared the
      precursor and mature forms of recombinant human IL-1alpha, IL-1beta, and IL-33
      proteins on the induction of cytokines from A549 cells as well as from human
      peripheral blood mononuclear cells (PBMC). Similar to the mature form, the IL
      1alpha precursor was active in inducing IL-6 and TNFalpha, whereas the precursor
      forms of IL-1beta and IL-33 were not active. On PBMC, precursor and mature IL
      1alpha at 0.04 and 0.2 nM were equally active in inducing IL-6. Given the fact
      that during necrotic cell death, the IL-1alpha precursor is released intact and
      triggers IL-1 receptors on tissue macrophages, these data identify the precursor
      form of IL-1alpha as a key player in sterile inflammation. 

PMID- 24312099
TI  - Plxnd1 expression in thymocytes regulates their intrathymic migration while that
      in thymic endothelium impacts medullary topology.
AB  - An important role for plexinD1 in thymic development is inferred from studies of
      germline Plxnd1 knockout (KO) mice where mislocalized CD69(+) thymocytes as well
      as ectopic thymic subcapsular medullary structures were observed. Given embryonic
      lethality of the Plxnd1 (-/-) genotype, fetal liver transplantation was employed
      in these prior analyses. Such embryonic hematopoietic reconstitution may have
      transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to
      Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we
      use Plxnd1 (flox/flox) mice crossed to pLck-Cre, pKeratin14-Cre, or pTek-Cre
      transgenic animals to create cell-type specific conditional knockout (CKO) lines
      involving thymocytes (D1ThyCKO), thymic epithelium (D1EpCKO), and thymic
      endothelium (D1EnCKO), respectively. These CKOs allowed us to directly assess the
      role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive
      (DP) thymocytes leads to their aberrant migration and cortical retention after
      TCR-mediated positive selection. In contrast, ectopic medulla formation is a
      consequence of loss of plexinD1 expression on endothelial cells, in turn linked
      to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither
      abnormality. Collectively, our findings underscore the non-redundant roles for
      plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla
      formation resulting from crosstalk between these thymic cellular components. 

PMID- 24312101
TI  - Ligands and receptors of the interleukin-1 family in immunity and disease.

PMID- 24312102
TI  - Emotional change-associated T cell mobilization at the early stage of a mouse
      model of multiple sclerosis.
AB  - Autoimmune diseases like multiple sclerosis (MS) are known to be associated with
      debilitating emotional disorders that manifest long before the flaring of motor
      dysfunctions. Given the emerging role of T cells in controlling both emotions and
      autoimmunity, in this study we explored possible correlation between T cell
      activation and changes in emotional behavior in a mouse model of MS. Our results
      showed a significant increase in blood circulating T cells as soon as at day 4
      post immunization. This lymphocytosis remained stable with time and preceded the
      infiltration of T cell in the CNS. The kinetic of T cell entry in the blood
      matched the kinetic of changes in behavior measured using the open field test.
      Treatment with glatiramer acetate, a well-known immunomodulatory drug for MS,
      suppressed behavioral changes while retaining the T cells in the draining lymph
      nodes. Together these results provide evidence of a positive correlation between
      the emigration of T cells in circulation and changes in emotions during chronic
      inflammatory diseases. The validation of these findings in the clinic might help
      to better understand the cause of the emotional and psychological burden of
      patients suffering MS or other autoimmune diseases. Most importantly our study
      suggests novel therapeutic venues for the treatment of the emotional changes
      associated with autoimmunity. 

PMID- 24312103
TI  - Empirical and process-based approaches to climate-induced forest mortality
      models.

PMID- 24312100
TI  - NOD-Like Receptors in Lung Diseases.
AB  - The lung is a particularly vulnerable organ at the interface of the body and the
      exterior environment. It is constantly exposed to microbes and particles by
      inhalation. The innate immune system needs to react promptly and adequately to
      potential dangers posed by these microbes and particles, while at the same time
      avoiding extensive tissue damage. Nucleotide-binding oligomerization domain-like
      receptors (NLRs) represent a group of key sensors for microbes and damage in the
      lung. As such they are important players in various infectious as well as acute
      and chronic sterile inflammatory diseases, such as pneumonia, chronic obstructive
      pulmonary disease (COPD), acute lung injury/acute respiratory distress syndrome,
      pneumoconiosis, and asthma. Activation of most known NLRs leads to the production
      and release of pro-inflammatory cytokines, and/or to the induction of cell death.
      We will review NLR functions in the lung during infection and sterile
      inflammation. 

PMID- 24312104
TI  - Plant cell shape: modulators and measurements.
AB  - Plant cell shape, seen as an integrative output, is of considerable interest in
      various fields, such as cell wall research, cytoskeleton dynamics and
      biomechanics. In this review we summarize the current state of knowledge on cell
      shape formation in plants focusing on shape of simple cylindrical cells, as well
      as in complex multipolar cells such as leaf pavement cells and trichomes. We
      summarize established concepts as well as recent additions to the understanding
      of how cells construct cell walls of a given shape and the underlying processes.
      These processes include cell wall synthesis, activity of the actin and
      microtubule cytoskeletons, in particular their regulation by microtubule
      associated proteins, actin-related proteins, GTP'ases and their effectors, as
      well as the recently-elucidated roles of plant hormone signaling and vesicular
      membrane trafficking. We discuss some of the challenges in cell shape research
      with a particular emphasis on quantitative imaging and statistical analysis of
      shape in 2D and 3D, as well as novel developments in this area. Finally, we
      review recent examples of the use of novel imaging techniques and how they have
      contributed to our understanding of cell shape formation. 

PMID- 24312105
TI  - Cytokinin cross-talking during biotic and abiotic stress responses.
AB  - As sessile organisms, plants have to be able to adapt to a continuously changing
      environment. Plants that perceive some of these changes as stress signals
      activate signaling pathways to modulate their development and to enable them to
      survive. The complex responses to environmental cues are to a large extent
      mediated by plant hormones that together orchestrate the final plant response.
      The phytohormone cytokinin is involved in many plant developmental processes.
      Recently, it has been established that cytokinin plays an important role in
      stress responses, but does not act alone. Indeed, the hormonal control of plant
      development and stress adaptation is the outcome of a complex network of multiple
      synergistic and antagonistic interactions between various hormones. Here, we
      review the recent findings on the cytokinin function as part of this hormonal
      network. We focus on the importance of the crosstalk between cytokinin and other
      hormones, such as abscisic acid, jasmonate, salicylic acid, ethylene, and auxin
      in the modulation of plant development and stress adaptation. Finally, the impact
      of the current research in the biotechnological industry will be discussed. 

PMID- 24312106
TI  - Mechanisms guiding Polycomb activities during gene silencing in Arabidopsis
      thaliana.
AB  - Polycomb group (PcG) proteins act in an evolutionarily conserved epigenetic
      pathway that regulates chromatin structures in plants and animals, repressing
      many developmentally important genes by modifying histones. PcG proteins can form
      at least two multiprotein complexes: Polycomb Repressive Complexes 1 and 2 (PRC1
      and PRC2, respectively). The functions of Arabidopsis thaliana PRCs have been
      characterized in multiple stages of development and have diverse roles in
      response to environmental stimuli. Recently, the mechanism that precisely
      regulates Arabidopsis PcG activity was extensively studied. In this review, we
      summarize recent discoveries in the regulations of PcG at the three different
      layers: the recruitment of PRCs to specific target loci, the polyubiquitination
      and degradation of PRC2, and the antagonism of PRC2 activity by the Trithorax
      group proteins. Current knowledge indicates that the powerful activity of the PcG
      pathway is strictly controlled for specific silencing of target genes during
      plant development and in response to environmental stimuli. 

PMID- 24312107
TI  - Transcriptome analysis of poplar rust telia reveals overwintering adaptation and
      tightly coordinated karyogamy and meiosis processes.
AB  - Most rust fungi have a complex life cycle involving up to five different spore
      producing stages. The telial stage that produces melanized overwintering
      teliospores is one of these and plays a fundamental role for generating genetic
      diversity as karyogamy and meiosis occur at that stage. Despite the importance of
      telia for the rust life cycle, almost nothing is known about the fungal genetic
      programs that are activated in this overwintering structure. In the present
      study, the transcriptome of telia produced by the poplar rust fungus Melampsora
      larici-populina has been investigated using whole genome exon oligoarrays and RT
      qPCR. Comparative expression profiling at the telial and uredinial stages
      identifies genes specifically expressed or up-regulated in telia including
      osmotins/thaumatin-like proteins (TLPs) and aquaporins that may reflect specific
      adaptation to overwintering as well numerous lytic enzymes acting on plant cell
      wall, reflecting extensive cell wall remodeling at that stage. The temporal
      dynamics of karyogamy was followed using combined RT-qPCR and DAPI-staining
      approaches. This reveals that fusion of nuclei and induction of karyogamy-related
      genes occur simultaneously between the 25 and 39 days post inoculation time
      frame. Transcript profiling of conserved meiosis genes indicates a preferential
      induction right after karyogamy and corroborates that meiosis begins prior to
      overwintering and is interrupted in Meiosis I (prophase I, diplonema stage) until
      teliospore germination in early spring. 

PMID- 24312108
TI  - Is the fluid mosaic (and the accompanying raft hypothesis) a suitable model to
      describe fundamental features of biological membranes? What may be missing?
AB  - The structure, dynamics, and stability of lipid bilayers are controlled by
      thermodynamic forces, leading to overall tensionless membranes with a distinct
      lateral organization and a conspicuous lateral pressure profile. Bilayers are
      also subject to built-in curvature-stress instabilities that may be released
      locally or globally in terms of morphological changes leading to the formation of
      non-lamellar and curved structures. A key controller of the bilayer's propensity
      to form curved structures is the average molecular shape of the different lipid
      molecules. Via the curvature stress, molecular shape mediates a coupling to
      membrane-protein function and provides a set of physical mechanisms for formation
      of lipid domains and laterally differentiated regions in the plane of the
      membrane. Unfortunately, these relevant physical features of membranes are often
      ignored in the most popular models for biological membranes. Results from a
      number of experimental and theoretical studies emphasize the significance of
      these fundamental physical properties and call for a refinement of the fluid
      mosaic model (and the accompanying raft hypothesis). 

PMID- 24312109
TI  - Thylakoid biogenesis has joined the new era of bacterial cell biology.

PMID- 24312110
TI  - Homologs of the yeast Tvp38 vesicle-associated protein are conserved in
      chloroplasts and cyanobacteria.
AB  - Vesicle transfer processes in eukaryotes depend on specific proteins, which
      mediate the selective packing of cargo molecules for subsequent release out of
      the cells after vesicle fusion to the plasma membrane. The protein Tvp38 is
      conserved in yeasts and higher eukaryotes and potentially involved in vesicle
      transfer processes at the Golgi membrane. Members of the so-called "SNARE
      associated proteins of the Tvp38-family" have also been identified in prokaryotes
      and those belong to the DedA protein family. Tvp38/DedA proteins are also
      conserved in cyanobacteria and chloroplasts. While only a single member of this
      family appears to be present in chloroplasts, cyanobacterial genomes typically
      encode multiple homologous proteins. Mainly based on our understanding of the
      DedA-homologous proteins of Escherichia coli, it appears likely that the function
      of these proteins in chloroplast and cyanobacteria involves stabilizing and
      organizing the structure of internal membrane systems. 

PMID- 24312111
TI  - Differential regulation of two types of monogalactosyldiacylglycerol synthase in
      membrane lipid remodeling under phosphate-limited conditions in sesame plants.
AB  - Phosphate (Pi) limitation causes drastic lipid remodeling in plant membranes.
      Glycolipids substitute for the phospholipids that are degraded, thereby supplying
      Pi needed for essential biological processes. Two major types of remodeling of
      membrane lipids occur in higher plants: whereas one involves an increase in the
      concentration of sulfoquinovosyldiacylglycerol in plastids to compensate for a
      decreased concentration of phosphatidylglycerol, the other involves
      digalactosyldiacylglycerol (DGDG) synthesis in plastids and the export of DGDG to
      extraplastidial membranes to compensate for reduced abundances of phospholipids.
      Lipid remodeling depends on an adequate supply of monogalactosyldiacylglycerol
      (MGDG), which is a substrate that supports the elevated rate of DGDG synthesis
      that is induced by low Pi availability. Regulation of MGDG synthesis has been
      analyzed most extensively using the model plant Arabidopsis thaliana, although
      orthologous genes that encode putative MGDG synthases exist in photosynthetic
      organisms from bacteria to higher plants. We recently hypothesized that two types
      of MGDG synthase diverged after the appearance of seed plants. This divergence
      might have both enabled plants to adapt to a wide range of Pi availability in
      soils and contributed to the diversity of seed plants. In the work presented
      here, we found that membrane lipid remodeling also takes place in sesame, which
      is one of the most common traditional crops grown in Asia. We identified two
      types of MGDG synthase from sesame (encoded by SeMGD1 and SeMGD2) and analyzed
      their enzymatic properties. Our results show that both genes correspond to the
      Arabidopsis type-A and -B isoforms of MGDG synthase. Notably, whereas Pi
      limitation up-regulates only the gene encoding the type-B isoform of Arabidopsis,
      low Pi availability up-regulates the expression of both SeMGD1 and SeMGD2. We
      discuss the significance of the different responses to low Pi availability in
      sesame and Arabidopsis. 

PMID- 24312112
TI  - Regulation of reactive oxygen species-mediated abscisic acid signaling in guard
      cells and drought tolerance by glutathione.
AB  - The phytohormone abscisic acid (ABA) induces stomatal closure in response to
      drought stress, leading to reduction of transpirational water loss. A thiol
      tripeptide glutathione (GSH) is an important regulator of cellular redox
      homeostasis in plants. Although it has been shown that cellular redox state of
      guard cells controls ABA-mediated stomatal closure, roles of GSH in guard cell
      ABA signaling were largely unknown. Recently we demonstrated that GSH functions
      as a negative regulator of ABA signaling in guard cells. In this study we
      performed more detailed analyses to reveal how GSH regulates guard cell ABA
      signaling using the GSH-deficient Arabidopsis mutant cad2-1. The cad2-1 mutant
      exhibited reduced water loss from rosette leaves. Whole-cell current recording
      using patch clamp technique revealed that the cad2-1 mutation did not affect ABA
      regulation of S-type anion channels. We found enhanced activation of Ca(2+)
      permeable channels by hydrogen peroxide (H2O2) in cad2-1 guard cells. The cad2-1
      mutant showed enhanced H2O2-induced stomatal closure and significant increase of
      ROS accumulation in whole leaves in response to ABA. Our findings provide a new
      understanding of guard cell ABA signaling and a new strategy to improve plant
      drought tolerance. 

PMID- 24312113
TI  - Lignocellulosic feedstocks: research progress and challenges in optimizing
      biomass quality and yield.

PMID- 24312114
TI  - Induced plant responses to microbes and insects.

PMID- 24312115
TI  - Increasing the power of association studies with affected families, unrelated
      cases and controls.
AB  - When studying the genetics of inherited diseases, researchers often collect data
      on affected families, unrelated cases, and healthy controls. However, the joint
      analysis of such heterogeneous data is difficult, and the simpler analysis of
      homogeneous subsets is often suboptimal. For example, while case-control tests of
      association are sensitive to allele frequency differences, the preferential
      transmission of risk alleles from heterozygous parents to their affected
      offspring is typically ignored. Similarly, the transmission disequilibrium test
      (TDT) fails to incorporate the difference in allele frequencies when testing for
      association. To boost the power of modern genetic studies, we propose POPFAM - a
      fast and efficient test of association that can accommodate large affected
      families, unrelated cases, and controls. We use simulations to assess the type I
      error and power of POPFAM across different genetic models, and minor allele
      frequencies. For comparison, we examine the power of competing methods: the trend
      test, a Wald test (equivalent to the TDT), and SCOUT. Our results show that
      POPFAM maintains the correct type I error, and that it is more powerful than the
      trend test or the TDT. It performs as well as, or better than the likelihood
      ratio test SCOUT, which was developed specifically for case-parent/case-control
      data. Furthermore, when applied to the human leukocyte antigen genotypes of 401
      type 1 diabetic families, POPFAM confirmed the previously reported association
      between DRB1(*)03:01 and microvascular complications (p = 0.04). In general, we
      expect our proposed test to facilitate the identification of clinically important
      genomic regions, and to better inform the design of follow-up sequencing efforts.

PMID- 24312116
TI  - The power of regional heritability analysis for rare and common variant
      detection: simulations and application to eye biometrical traits.
AB  - Genome-wide association studies (GWAS) have provided valuable insights into the
      genetic basis of complex traits. However, they have explained relatively little
      trait heritability. Recently, we proposed a new analytical approach called
      regional heritability mapping (RHM) that captures more of the missing genetic
      variation. This method is applicable both to related and unrelated populations.
      Here, we demonstrate the power of RHM in comparison with single-SNP GWAS and gene
      based association approaches under a wide range of scenarios with variable
      numbers of quantitative trait loci (QTL) with common and rare causal variants in
      a narrow genomic region. Simulations based on real genotype data were performed
      to assess power to capture QTL variance, and we demonstrate that RHM has greater
      power to detect rare variants and/or multiple alleles in a region than other
      approaches. In addition, we show that RHM can capture more accurately the QTL
      variance, when it is caused by multiple independent effects and/or rare variants.
      We applied RHM to analyze three biometrical eye traits for which single-SNP GWAS
      have been published or performed to evaluate the effectiveness of this method in
      real data analysis and detected some additional loci which were not detected by
      other GWAS methods. RHM has the potential to explain some of missing heritability
      by capturing variance caused by QTL with low MAF and multiple independent QTL in
      a region, not captured by other GWAS methods. RHM analyses can be implemented
      using the software REACTA (http://www.epcc.ed.ac.uk/projects-portfolio/reacta). 

PMID- 24312117
TI  - Genome-wide multi-omics profiling of colorectal cancer identifies immune
      determinants strongly associated with relapse.
AB  - The use and benefit of adjuvant chemotherapy to treat stage II colorectal cancer
      (CRC) patients is not well understood since the majority of these patients are
      cured by surgery alone. Identification of biological markers of relapse is a
      critical challenge to effectively target treatments to the ~20% of patients
      destined to relapse. We have integrated molecular profiling results of several
      "omics" data types to determine the most reliable prognostic biomarkers for
      relapse in CRC using data from 40 stage I and II CRC patients. We identified 31
      multi-omics features that highly correlate with relapse. The data types were
      integrated using multi-step analytical approach with consecutive elimination of
      redundant molecular features. For each data type a systems biology analysis was
      performed to identify pathways biological processes and disease categories most
      affected in relapse. The biomarkers detected in tumors urine and blood of
      patients indicated a strong association with immune processes including aberrant
      regulation of T-cell and B-cell activation that could lead to overall differences
      in lymphocyte recruitment for tumor infiltration and markers indicating
      likelihood of future relapse. The immune response was the biologically most
      coherent signature that emerged from our analyses among several other biological
      processes and corroborates other studies showing a strong immune response in
      patients less likely to relapse. 

PMID- 24312118
TI  - Association testing to detect gene-gene interactions on sex chromosomes in trio
      data.
AB  - Autism Spectrum Disorder (ASD) occurs more often among males than females in a
      4:1 ratio. Among theories used to explain the causes of ASD, the X chromosome and
      the Y chromosome theories attribute ASD to the X-linked mutation and the male
      limited gene expressions on the Y chromosome, respectively. Despite the rationale
      of the theory, studies have failed to attribute the sex-biased ratio to the
      significant linkage or association on the regions of interest on X chromosome. We
      further study the gender biased ratio by examining the possible interaction
      effects between two genes in the sex chromosomes. We propose a logistic
      regression model with mixed effects to detect gene-gene interactions on sex
      chromosomes. We investigated the power and type I error rates of the approach for
      a range of minor allele frequencies and varying linkage disequilibrium between
      markers and QTLs. We also evaluated the robustness of the model to population
      stratification. We applied the model to a trio-family data set with an ASD
      affected male child to study gene-gene interactions on sex chromosomes. 

PMID- 24312120
TI  - Testing for direct genetic effects using a screening step in family-based
      association studies.
AB  - In genome wide association studies (GWAS), family-based studies tend to have less
      power to detect genetic associations than population-based studies, such as case
      control studies. This can be an issue when testing if genes in a family-based
      GWAS have a direct effect on the phenotype of interest over and above their
      possible indirect effect through a secondary phenotype. When multiple SNPs are
      tested for a direct effect in the family-based study, a screening step can be
      used to minimize the burden of multiple comparisons in the causal analysis. We
      propose a 2-stage screening step that can be incorporated into the family-based
      association test (FBAT) approach similar to the conditional mean model approach
      in the Van Steen-algorithm (Van Steen et al., 2005). Simulations demonstrate that
      the type 1 error is preserved and this method is advantageous when multiple
      markers are tested. This method is illustrated by an application to the
      Framingham Heart Study. 

PMID- 24312119
TI  - Enhancing systems medicine beyond genotype data by dynamic patient signatures:
      having information and using it too.
AB  - In order to establish systems medicine, based on the results and insights from
      basic biological research applicable for a medical and a clinical patient care,
      it is essential to measure patient-based data that represent the molecular and
      cellular state of the patient's pathology. In this paper, we discuss potential
      limitations of the sole usage of static genotype data, e.g., from next-generation
      sequencing, for translational research. The hypothesis advocated in this paper is
      that dynOmics data, i.e., high-throughput data that are capable of capturing
      dynamic aspects of the activity of samples from patients, are important for
      enabling personalized medicine by complementing genotype data. 

PMID- 24312121
TI  - The null distribution of likelihood-ratio statistics in the conditional-logistic
      linkage model.
AB  - Olson's conditional-logistic model retains the nice property of the LOD score
      formulation and has advantages over other methods that make it an appropriate
      choice for complex trait linkage mapping. However, the asymptotic distribution of
      the conditional-logistic likelihood-ratio (CL-LR) statistic with genetic
      constraints on the model parameters is unknown for some analysis models, even in
      the case of samples comprising only independent sib pairs. We derive
      approximations to the asymptotic null distributions of the CL-LR statistics and
      compare them with the empirical null distributions by simulation using
      independent affected sib pairs. Generally, the empirical null distributions of
      the CL-LR statistics match well the known or approximated asymptotic
      distributions for all analysis models considered except for the covariate model
      with a minimum-adjusted binary covariate. This work will provide useful
      guidelines for linkage analysis of real data sets for the genetic analysis of
      complex traits, thereby contributing to the identification of genes for disease
      traits. 

PMID- 24312122
TI  - Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met
      polymorphisms are associated with rumination and co-rumination in adolescents.
AB  - BACKGROUND: Despite research supporting moderate heritability of depression,
      efforts to replicate candidate gene associations to depression have yielded
      inconsistent results. We tested whether Val66Met and 5-HTTLPR exhibit utility as
      genetic markers of depression risk, testing for replicable associations to
      cognitive and interpersonal endophenotypes of depression (rumination and co
      rumination), and further exploring developmental and sex moderation. METHOD: In
      Study I, 228 youth (ages 8-14) of mothers with or without a history of MDD during
      the child's lifetime were recruited from the community. Replication tests were
      carried out in Study II, a sample of 87 youth with similar recruitment. RESULTS:
      In Study I, the Val66Met single-nucleotide polymorphism (SNP) was associated with
      rumination in adolescents, but not children, such that adolescents homozygous for
      the Val allele reported higher rumination levels. Further, a cumulative genetic
      score (CGS) (Val66Val and 5-HTTLPR) predicted higher levels of co-rumination,
      specifically among adolescent girls. Both genetic associations maintained
      significance after covarying for current depressive symptomology, and the other
      endophenotype. Finally, both genetic associations exhibited similar effect sizes
      in Study II, although results did not reach statistical significance.
      CONCLUSIONS: RESULTS replicate a previously reported association between the
      brain derived neurotrophic factor (BDNF) Val allele and rumination in
      adolescents, and provide preliminary support for a CGS predictive of co
      rumination in adolescent girls. The current study indicates that candidate genes
      may demonstrate utility as consistent genetic markers of depression risk when
      focused on specific phenotypes, and supports the need to explore potential
      differential effects of developmental stage and sex. However, given the small
      sample sizes and possibility of chance findings, these results should be
      interpreted with caution pending replication.

PMID- 24312124
TI  - The National DNA Data Bank of Canada: a Quebecer perspective.
AB  - The Canadian National DNA Database was created in 1998 and first used in the mid
      2000. Under management by the RCMP, the National DNA Data Bank of Canada offers
      each year satisfactory reported statistics for its use and efficiency. Built on
      two indexes (convicted offenders and crime scene indexes), the database not only
      provides increasing matches to offenders or linked traces to the various police
      forces of the nation, but offers a memory repository for cold cases. Despite
      these achievements, the data bank is now facing new challenges that will
      inevitably defy the way the database is currently used. These arise from the
      increasing power of detection of DNA traces, the diversity of demands from police
      investigators and the growth of the bank itself. Examples of new requirements
      from the database now include familial searches, low-copy-number analyses and the
      correct interpretation of mixed samples. This paper aims to develop on the
      original way set in Quebec to address some of these challenges. Nevertheless,
      analytic and technological advances will inevitably lead to the introduction of
      new technologies in forensic laboratories, such as single cell sequencing,
      phenotyping, and proteomics. Furthermore, it will not only request a new
      holistic/global approach of the forensic molecular biology sciences (through
      academia and a more investigative role in the laboratory), but also new legal
      developments. Far from being exhaustive, this paper highlights some of the
      current use of the database, its potential for the future, and opportunity to
      expand as a result of recent technological developments in molecular biology,
      including, but not limited to DNA identification. 

PMID- 24312125
TI  - Long non-coding RNAs in hematologic malignancies: road to translational research.

PMID- 24312123
TI  - Trophoblasts, invasion, and microRNA.
AB  - MicroRNAs (miRNAs) have recently become essential actors in various fields of
      physiology and medicine, especially as easily accessible circulating biomarkers,
      or as modulators of cell differentiation. To this respect, terminal
      differentiation of trophoblasts (the characteristic cells of the placenta in
      Therian mammals) into syncytiotrophoblast, villous trophoblast, or extravillous
      trophoblast constitutes a good example of such a choice, where miRNAs have
      recently been shown to play an important role. The aim of this review is to
      provide a snapshot of what is known today in placentation mechanisms that are
      mediated by miRNA, under the angles of materno-fetal immune dialog regulation,
      trophoblast differentiation, and angiogenesis at the materno-fetal interface.
      Also, two aspects of regulation of these issues will be highlighted: the part
      played by oxygen concentration and the specific function of imprinted genes in
      the developing placenta. 

PMID- 24312126
TI  - Evaluation of the effects of titanium dioxide nanoparticles on cultured Rana
      catesbeiana tailfin tissue.
AB  - Nanoparticles (NPs), materials that have one dimension less than 100 nm, are used
      in manufacturing, health, and food products, and consumer products including
      cosmetics, clothing, and household appliances. Their utility to industry is
      derived from their high surface-area-to-volume ratios and physico-chemical
      properties distinct from their bulk counterparts, but the near-certainty that NPs
      will be released into the environment raises the possibility that they could
      present health risks to humans and wildlife. The thyroid hormones (THs),
      thyroxine, and 3,3',5-triiodothyronine (T3), are involved in development and
      metabolism in vertebrates including humans and frogs. Many of the processes of
      anuran metamorphosis are analogous to human post-embryonic development and
      disruption of TH action can have drastic effects. These shared features make the
      metamorphosis of anurans an excellent model for screening for endocrine
      disrupting chemicals (EDCs). We used the cultured tailfin (C-fin) assay to
      examine the exposure effects of 0.1-10 nM (~8-800 ng/L) of three types of ~20 nm
      TiO2 NPs (P25, M212, M262) and micron-sized TiO2 (MU TiO2) +/-10 nM T3. The
      actual Ti levels were 40.9-64.7% of the nominal value. Real-time quantitative
      polymerase chain reaction (QPCR) was used to measure the relative amounts of mRNA
      transcripts encoding TH-responsive THs receptors (thra and thrb) and Rana larval
      keratin type I (rlk1), as well as the cellular stress-responsive heat shock
      protein 30 kDa (hsp30), superoxide dismutase (sod), and catalase (cat). The
      levels of the TH-responsive transcripts were largely unaffected by any form of
      TiO2. Some significant effects on stress-related transcripts were observed upon
      exposure to micron-sized TiO2, P25, and M212 while no effect was observed with
      M262 exposure. Therefore, the risk of adversely affecting amphibian tissue by
      disrupting TH-signaling or inducing cellular stress is low for these compounds
      relative to other previously-tested NPs. 

PMID- 24312127
TI  - Efficacy of robotic-assisted prostatectomy in localized prostate cancer: a
      systematic review of clinical trials.
AB  - Background. Radical prostatectomy is an effective treatment for clinically
      localized prostate cancer. The three approaches in current use have been
      extensively compared in observational studies, which have methodological
      limitations. Objective. To compare the efficacy and safety of three radical
      prostatectomy approaches in patients with localized prostate cancer: open,
      laparoscopic, and robotic-assisted laparoscopic surgery. Materials and Methods. A
      systematic review of the literature was carried out. Databases MEDLINE, EMBASE,
      LILACS, and CENTRAL were searched for randomized clinical trials that directly
      compared two or more radical prostatectomy approaches. Selection criteria,
      methodological rigor, and risk of bias were evaluated by two independent
      researchers using Cochrane Collaboration's tools. Results. Three trials were
      included. In one study, laparoscopic surgery was associated with fewer blood loss
      and transfusion rates than the open procedure, in spite of longer operating time.
      The other two trials compared laparoscopic and robotic-assisted surgery in which
      no differences in perioperative outcomes were detected. Nevertheless, robotic
      assisted prostatectomy showed more favorable erectile function and urinary
      continence recovery. Conclusion. At the present time, no clear advantage can be
      attributed to any of the existing prostatectomy approaches in terms of oncologic
      outcomes. However, some differences in patient-related outcomes favor the newer
      methods. Larger trials are required. 

PMID- 24312129
TI  - Human adipose tissue derived stem cells promote liver regeneration in a rat model
      of toxic injury.
AB  - In the light of the persisting lack of donor organs and the risks of
      allotransplantations, the possibility of liver regeneration with autologous stem
      cells from adipose tissue (ADSC) is an intriguing alternative. Using a model of a
      toxic liver damage in Sprague Dawley rats, generated by repetitive
      intraperitoneal application of retrorsine and allyl alcohol, the ability of human
      ADSC to support the restoration of liver function was investigated. A two-thirds
      hepatectomy was performed, and human ADSC were injected into one remaining liver
      lobe in group 1 (n = 20). Injection of cell culture medium performed in group 2
      (n = 20) served as control. Cyclosporine was applied to achieve immunotolerance.
      Blood samples were drawn weekly after surgery to determine liver-correlated blood
      values. Six and twelve weeks after surgery, animals were sacrificed and
      histological sections were analyzed. ADSC significantly raised postoperative
      albumin (P < 0.017), total protein (P < 0.031), glutamic oxaloacetic transaminase
      (P < 0.001), and lactate dehydrogenase (P < 0.04) levels compared to injection of
      cell culture medium alone. Transplanted cells could be found up to twelve weeks
      after surgery in histological sections. This study points towards ADSC being a
      promising alternative to hepatocyte or liver organ transplantation in patients
      with severe liver failure. 

PMID- 24312128
TI  - Primary spinal germ cell tumors: a case analysis and review of treatment
      paradigms.
AB  - Objective. Primary intramedullary spinal germ cell tumors are exceedingly rare.
      As such, there are no established treatment paradigms. We describe our management
      for spinal germ cell tumors and a review of the literature. Clinical
      Presentation. We describe the case of a 45-year-old man with progressive lower
      extremity weakness and sensory deficits. He was found to have enhancing
      intramedullary mass lesions in the thoracic spinal cord, and pathology was
      consistent with an intramedullary germ cell tumor. A video presentation of the
      case and surgical approach is provided. Conclusion. As spinal cord germinomas are
      highly sensitive to radiation and chemotherapy, a patient can be spared radical
      surgery. Diverse treatment approaches exist across institutions. We advocate
      biopsy followed by local radiation, with or without adjuvant chemotherapy, as the
      optimal treatment for these tumors. Histological findings have prognostic value
      if syncytiotrophoblastic giant cells (STGCs) are found, which are associated with
      a higher rate of recurrence. The recurrence rate in STGC-positive spinal
      germinomas is 33% (2/6), whereas it is only 8% in STGC-negative tumors (2/24). We
      advocate limited volume radiotherapy combined with systemic chemotherapy in
      patients with high risk of recurrence. To reduce endocrine and neurocognitive
      side effects, cranio-spinal radiation should be used as a last resort in patients
      with recurrence. 

PMID- 24312130
TI  - Combination of human leukocyte antigen and killer cell immunoglobulin-like
      receptor genetic background influences the onset age of hepatocellular carcinoma
      in male patients with hepatitis B virus infection.
AB  - To investigate whether killer cell immunoglobulin-like receptor (KIR) and human
      leukocyte antigen (HLA) genetic background could influence the onset age of
      hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)
      infection, one hundred and seventy-one males with HBV-related HCC were enrolled.
      The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci
      were genotyped with high resolution by a routine sequence-based typing method.
      The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined
      individually by Kaplan-Meier (KM) analysis. Multivariate Cox hazard regression
      model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk
      factor for earlier onset age of HCC (median onset age was 44 for C1C1
      KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P = 0.04 for
      KM analysis; HR = 1.70, P = 0.004 for multivariate Cox model). We conclude that
      KIR and HLA genetic background can influence the onset age of HCC in male
      patients with HBV infection. This study may be useful to improve the current HCC
      surveillance program in HBV-infected patients. Our findings also suggest an
      important role of natural killer cells (or other KIR-expressing cells) in the
      progress of HBV-related HCC development. 

PMID- 24312132
TI  - Body-Efficacy Expectation: Assessment of Beliefs concerning Bodily Coping
      Capabilities with a Five-Item Scale.
AB  - Background. Expectancies regarding a treatment play an important role in recovery
      as has been shown in placebo research. The role of expectations regarding the
      bodily capability to overcome illness is less investigated although in
      complementary and alternative medicine (CAM) such capability is the target of
      interventions. We introduced a new construct, body-efficacy expectation, defined
      as the conviction that one's body is able to deal with health-threatening factors
      by itself, and developed and validated a scale for its measurement. Methods. The
      scale was developed following expert recommendations. Using online survey data
      from 1054 participants an exploratory factor analysis was conducted and
      psychometric properties of the scale were examined (item characteristics,
      reliability, and validity). Results. The exploratory factor analysis yielded a
      one-factor solution explaining 51.96% of total variance (Cronbach's alpha =
      0.77). One of the originally six items was removed due to poor item
      characteristics. Correlations with several validation measures were in line with
      the theoretical background of the construct. Most importantly, participants with
      better general health showed higher body-efficacy expectation than participants
      with poorer health status. Conclusions. Further studies confirming the factor
      structure and using clinical samples are recommended. Also, the relations with
      the appraisal of CAM and CAM use warrant further research. 

PMID- 24312131
TI  - An elucidation of neutrophil functions against Mycobacterium tuberculosis
      infection.
AB  - We characterized the functions of neutrophils in response to Mycobacterium
      tuberculosis (M. tb) infection, with particular reference to glutathione (GSH).
      We examined the effects of GSH in improving the ability of neutrophils to control
      intracellular M. tb infection. Our findings indicate that increasing the
      intracellular levels of GSH with a liposomal formulation of GSH (L-GSH) resulted
      in reduction in the levels of free radicals and increased acidification of M. tb
      containing phagosomes leading to the inhibition in the growth of M. tb. This
      inhibitory mechanism is dependent on the presence of TNF-alpha and IL-6. Our
      studies demonstrate a novel regulatory mechanism adapted by the neutrophils to
      control M. tb infection.

PMID- 24312133
TI  - Clinical research of traditional chinese medicine needs to develop its own system
      of core outcome sets.
AB  - Currently, quality issues concerning clinical research of traditional Chinese
      medicine (TCM) have come into the spotlight. It has been recognized that poorly
      devised research methodology largely restricted the development of clinical
      research in TCM. The choice of appropriate outcome measurements is key to the
      success of clinical research; however, the current procedure for outcomes
      selection in clinical research of TCM is problematic due to the underdevelopment
      of clinical methodology. Under this circumstance, we propose the introduction to
      the concept of Core Outcome Set (COS) and discuss the feasibility of developing a
      COS system that caters for clinical studies in TCM, in the hope that the outcome
      evaluation system could be up to international standards. 

PMID- 24312134
TI  - Automatic sex determination of skulls based on a statistical shape model.
AB  - Sex determination from skeletons is an important research subject in forensic
      medicine. Previous skeletal sex assessments are through subjective visual
      analysis by anthropologists or metric analysis of sexually dimorphic features. In
      this work, we present an automatic sex determination method for 3D digital
      skulls, in which a statistical shape model for skulls is constructed, which
      projects the high-dimensional skull data into a low-dimensional shape space, and
      Fisher discriminant analysis is used to classify skulls in the shape space. This
      method combines the advantages of metrical and morphological methods. It is easy
      to use without professional qualification and tedious manual measurement. With a
      group of Chinese skulls including 127 males and 81 females, we choose 92 males
      and 58 females to establish the discriminant model and validate the model with
      the other skulls. The correct rate is 95.7% and 91.4% for females and males,
      respectively. Leave-one-out test also shows that the method has a high accuracy. 

PMID- 24312135
TI  - Variable selection in ROC regression.
AB  - Regression models are introduced into the receiver operating characteristic (ROC)
      analysis to accommodate effects of covariates, such as genes. If many covariates
      are available, the variable selection issue arises. The traditional induced
      methodology separately models outcomes of diseased and nondiseased groups; thus,
      separate application of variable selections to two models will bring barriers in
      interpretation, due to differences in selected models. Furthermore, in the ROC
      regression, the accuracy of area under the curve (AUC) should be the focus
      instead of aiming at the consistency of model selection or the good prediction
      performance. In this paper, we obtain one single objective function with the
      group SCAD to select grouped variables, which adapts to popular criteria of model
      selection, and propose a two-stage framework to apply the focused information
      criterion (FIC). Some asymptotic properties of the proposed methods are derived.
      Simulation studies show that the grouped variable selection is superior to
      separate model selections. Furthermore, the FIC improves the accuracy of the
      estimated AUC compared with other criteria. 

PMID- 24312136
TI  - Continuous Glucose Monitoring Versus Self-monitoring of Blood Glucose in Children
      with Type 1 Diabetes- Are there Pros and Cons for Both?
AB  - Glucose monitoring is essential for modern diabetes treatment and the achievement
      of near-normal glycemic control. Monitoring provides the data necessary for
      patients to make daily management decisions related to food intake, insulin dose,
      and physical exercise and can enable patients to avoid potentially dangerous
      episodes of hypo- and hyperglycemia. Additionally, monitoring can provide health
      care providers with the information needed to identify glycemic patterns, educate
      patients, and adjust insulin. Presently, youth with type 1 diabetes can self
      monitor blood glucose via home blood glucose meters or monitor glucose
      concentrations nearly continuously using a continuous glucose monitor. There are
      advantages and disadvantages to the use of either of these technologies. This
      review describes the two technologies and the research supporting their use in
      the management of youth with type 1 diabetes in order to weigh their relative
      costs and benefits.

PMID- 24312137
TI  - Direct Mass Spectrometry Analysis of Untreated Samples of Ultralow Amounts Using
      Extraction Nano-Electrospray.
AB  - Direct mass spectrometry analysis of untreated samples of volumes as low as 0.2
      uL were achieved using fast extraction and nanoESI (electrospray ionization) in a
      combined fashion. The analytes in dried samples on paper substrates were
      extracted by organic solvent in a nanoESI tube and ionized with a high voltage
      applied for generating a spray. The ionization source produced stable signals for
      different atmospheric pressure interfaces of triple quadrupole instruments.
      Analysis time more than 20 minutes were available with 10 uL solvent consumed for
      the entire analysis process. The performance in qualitative and quantitative
      analysis was characterized with a wide variety of samples. Limits of detection as
      low as 0.1 ng/mL (corresponding to an absolute amount of 0.05 pg) were obtained
      for analysis of atrazine in river water, thiabendazole in orange homogenate, and
      methamphetamine in blood.

PMID- 24312138
TI  - Sex disparities in the association of lung adenocarcinoma with colorectal cancer.
AB  - BACKGROUND: Most cancers share common risk factors. It might provide evidence of
      shared risk factors with cancers by investigating cross-country and cross
      township comparisons. METHODS: The data were obtained from International
      Association of Cancer Registries/World Health Organization and the National
      Cancer Registration Program of Taiwan. Age standardized incidence rates were
      calculated among gastric cancer, colorectal cancer and lung adenocarcinoma in 19
      countries from 1995 to 1998. The Pearson correlations were also compared among 3
      types of cancers for both sexes. RESULTS: The incidence rates of gastric and
      colorectal cancer throughout different countries show male dominance with a male
      to-female sex ratio of around 2 and 1.5, respectively. Significant cross-country
      correlations in colorectal cancer (r=0.918, p<0.001), gastric cancer (r=0.985,
      p<0.001) and lung adenocarcinoma (r=0.685, p=0.001) were observed between men and
      women. There was a significant international correlation between colorectal
      cancer and lung adenocarcinoma in men (r=0.526, p=0.021), but not in women. In
      cross-township comparisons of Taiwan, there were significant correlations in
      colorectal cancer (r=0.451, p<0.001), gastric cancer (r=0.486, p<0.001), and lung
      adenocarcinoma (r=0.217, p<0.001) between men and women. There were links of lung
      adenocarcinoma and gastric cancer (r=0.122, p=0.024) and colorectal cancer
      (r=0.128, p=0.018) in women, and lung adenocarcinoma and colorectal cancer in men
      (r=0.276, p<0.001). CONCLUSIONS: There were associations between lung
      adenocarcinoma and colorectal cancer between and in both sexes in Taiwan, but not
      in cross-country comparisons. The results suggest that some factor, like genes,
      may be important as determinants for the association between lung adenocarcinoma
      and colorectal cancer.

PMID- 24312139
TI  - Novel functional assay for spindle-assembly checkpoint by cyclin-dependent kinase
      activity to predict taxane chemosensitivity in breast tumor patient.
AB  - Taxanes are among the drugs most commonly used for preoperative chemotherapy for
      breast cancer. Taxanes induce mitotic arrest and subsequent apoptosis. The
      spindle-assembly checkpoint (SAC) is known to be activated during mitosis, along
      with cyclin-dependent kinase-1 (CDK1), and is required for taxane-induced cell
      death. We hypothesized that CDK1 activity predicts response to taxane-containing
      chemotherapy. This study included breast cancer patients who received
      preoperative chemotherapy- taxane-containing treatment followed by anthracycline
      based treatment-and then underwent surgery. Before starting taxane-containing
      chemotherapy, patients underwent fine-needle aspiration biopsy, and the biopsy
      samples were incubated in paclitaxel solution to measure CDK activity. Clinical
      were evaluated after taxane therapy, and pathological resposes were evaluated
      after completion of all preoperative chemotherapy. Thirty five patients were
      eligible for analysis of clinical response to taxane-containing therapy. Twenty
      six patients had taxane-sensitive and 9 taxane-resistant tumors. Using a cut-off
      of CDK activity determined by the ROC analysis, patients were classified into SAC
      function and dysfunction groups. Univariate logistic regression analysis with
      clinicopathologic parameters showed that only CDK-based SAC functionality was
      significantly correlated with clinical response (P =0.017). No significant
      correlation was observed between SAC functionality and pathologic response. CDK
      based SAC functionality significantly predicted clinical response (P =.0072,
      overall agreement = 71.4%), and this is a unique mechanism-based marker for
      predicting taxane chemosensitivity. Further, large prospective study is needed to
      determine CDK-based SAC functionality could be developed as a predictive
      biomarker. 

PMID- 24312140
TI  - Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic
      pathways and induction of apoptosis in breast cancer cells by a phytochemical
      super-cocktail: genes that underpin its mode of action.
AB  - Traditional chemotherapy and radiotherapy for cancer treatment face serious
      challenges such as drug resistance and toxic side effects. Complementary /
      Alternative medicine is increasingly being practiced worldwide due to its safety
      beneficial therapeutic effects. We hypothesized that a super combination (SC) of
      known phytochemicals used at bioavailable levels could induce 100% killing of
      breast cancer (BC) cells without toxic effects on normal cells and that
      microarray analysis would identify potential genes for targeted therapy of BC.
      Mesenchymal Stems cells (MSC, control) and two BC cell lines were treated with
      six well established pro-apoptotic phytochemicals individually and in combination
      (super cocktail), at bioavailable levels. The compounds were ineffective
      individually. In combination, they significantly suppressed BC cell proliferation
      (>80%), inhibited migration and invasion, caused cell cycle arrest and induced
      apoptosis resulting in 100% cell death. However, there were no deleterious
      effects on MSC cells used as control. Furthermore, the SC down-regulated the
      expression of PCNA, Rb, CDK4, BcL-2, SVV, and CD44 (metastasis inducing stem cell
      factor) in the BC cell lines. Microarray analysis revealed several differentially
      expressed key genes (PCNA, Rb, CDK4, Bcl-2, SVV, P53 and CD44) underpinning SC
      promoted BC cell death and motility. Four unique genes were highly up-regulated
      (ARC, GADD45B, MYLIP and CDKN1C). This investigation indicates the potential for
      development of a highly effective phytochemical combination for breast cancer
      chemoprevention / chemotherapy. The novel over-expressed genes hold the potential
      for development as markers to follow efficacy of therapy. 

PMID- 24312142
TI  - A Comparative Study of the effects of Vitamins C and E in the Development of
      Sarcoma 180 in Mice.
AB  - In this work we have investigated the effects of vitamins C and E on tumors via
      the mice xenotransplant model of sarcoma 180 (S180) in vivo. The experimental
      results suggest that dosages of 100 mg/kg vitamin C and 400 mg/kg vitamin E
      yields a great inhibitory behavior on tumors. 

PMID- 24312141
TI  - Apoptosis in Living Animals Is Assisted by Scavenger Cells and Thus May Not
      Mainly Go through the Cytochrome C-Caspase Pathway.
AB  - Because billions of cells die every day in their bodies, animals have
      evolutionarily developed apoptosis to preserve the tissue environment from
      adverse effects of dead cells, a process achieved via phagocytosis of the cell
      corpses by professional or amateur phagocytes that are collectively referred to
      as scavengers. Hence, apoptosis is a merger of two procedures separately
      occurring inside the dying and the scavenger cells, respectively. The task of
      apoptosis research is to study how these death procedures occur without hurting
      the host tissues, and recruitment of in vitro system into the study must be
      justified for this purpose. Cells in culture have no motivation to preserve the
      environment, and their death does not involve corpse clearance by scavengers.
      Therefore, programmed cell death in culture should be redefined, for example as
      stress-induced cell death, to avoid many sources of confusions, since the word
      "apoptosis" had already been defined, prior to the era of cell culture, as a
      silent and beneficial cell suicide with corpse clearance as a distinctive
      hallmark. We should start over again on apoptosis research by determining whether
      different physiological apoptotic procedures in animals involve the cytochrome c
      caspase pathway, since it has been established from cultured cells as a central
      mechanism of "apoptosis" but whether it overarches any physiological apoptotic
      procedure in animals is still unclear. Probably, cells in living animals are
      programmed to use scavengers to assist their apoptosis but cells in culture have
      no scavengers to help and thus need to go mainly through the cytochrome c-caspase
      pathway. 

PMID- 24312143
TI  - SRPK1 Dissimilarly Impacts on the Growth, Metastasis, Chemosensitivity and
      Angiogenesis of Glioma in Normoxic and Hypoxic Conditions.
AB  - Glioma is among the ten most common causes of cancer-related death and has no
      effective treatment for it, so we are trying to find a new target for anticancer
      treatment. This study investigates the different expression of SRPK1 as a novel
      protein in glioma, which can influence tumor cells biological characteristics in
      normoxic and hypoxic environment. The expression levels of SRPK1 protein in
      glioma cell lines transfected with siSRPK1 or not were examined using
      immunofluorescence, RT-PCR and Western blot analysis, respectively. The impact of
      SRPK1 on the biological characteristics of U251 cells was further studied using
      methylthiazol tetrazolium assays, flow cytometry, and Transwell invasion chamber
      assays. The results showed that knockdown of SRPK1 inhibited tumor cells growth,
      invasion and migration in normoxic condition, but portion of the effect could be
      reversed in hypoxia. SRPK1 expression was induced in glioma cells by DDP treated,
      but not TMZ, in both normoxia and hypoxia conditions. We propose SRPK1 as a new
      molecular player contributing to the early treatment of glioma. 

PMID- 24312146
TI  - Quantitative methods for molecular diagnostic and therapeutic imaging.
AB  - This theme issue provides an overview on the basic quantitative methods, an in
      depth discussion on the cutting-edge quantitative analysis approaches as well as
      their applications for both static and dynamic molecular diagnostic and
      therapeutic imaging. 

PMID- 24312145
TI  - Novel Phenotypic Fluorescent Three-Dimensional Co-Culture Platforms for
      Recapitulating Tumor in vivo Progression and for Personalized Therapy.
AB  - Because three-dimensional (3D) in vitro models are more accurate than 2D cell
      culture models and faster and cheaper than animal models, they have become a
      prospective trend in the biomedical and pharmaceutical fields, especially for
      personalized and targeted therapies. Because appropriate 3D models can be
      customized to mimic the in vivo microenvironment wherein various cell populations
      grow within an intricate but well organized extracellular matrix (ECM), they can
      accurately recapitulate physiological and pathophysiological progressions. The
      majority of cancers are carcinomas, which originate from epithelial cells, and
      dynamically interact with non-malignant cells including stromal cells
      (fibroblasts), vascular cells (endothelial cells and pericytes), immune cells
      (macrophages and mast cells), and the ECM. Employing a tumor monoclonal colony,
      tumor xenograft or patient cancer biopsy into an in vivo-like microenvironment,
      the native signaling pathways, cell-cell and cell-matrix interactions, and cell
      phenotypes are preserved and our fluorescent phenotypic 3D co-culture platforms
      can then accurately recapitulate the tumor in vivo scenario including tumor
      induced angiogenesis, tumor growth, and metastasis. In this paper, we describe a
      robust and standardized method to co-culture a tumor colony or biopsy with
      different cell populations, e.g., endothelial cells, immune cells, pericytes,
      etc. The procedures for recovering cells from the co-culture for molecular
      analyses, imaging, and analyzing are also described. We selected ECM solubilized
      extract derived from Engelbreth-Holm-Swam sarcoma cells. Because the 3D co
      culture platforms can provide drug chemosensitivity data within 9 days that is
      equivalent to the results generated from mouse tumor xenograft models in 50 days,
      the 3D co-culture platforms are more accurate, efficient, and cost-effective and
      may replace animal models in the near future to predict drug efficacy,
      personalize therapies, prevent drug resistance, and improve the quality of life. 

PMID- 24312147
TI  - Proton therapy verification with PET imaging.
AB  - Proton therapy is very sensitive to uncertainties introduced during treatment
      planning and dose delivery. PET imaging of proton induced positron emitter
      distributions is the only practical approach for in vivo, in situ verification of
      proton therapy. This article reviews the current status of proton therapy
      verification with PET imaging. The different data detecting systems (in-beam, in
      room and off-line PET), calculation methods for the prediction of proton induced
      PET activity distributions, and approaches for data evaluation are discussed. 

PMID- 24312144
TI  - Molecular Targeted Drugs and Biomarkers in NSCLC, the Evolving Role of
      Individualized Therapy.
AB  - Lung cancer first line treatment has been directed from the non-specific
      cytotoxic doublet chemotherapy to the molecular targeted. The major limitation of
      the targeted therapies still remains the small number of patients positive to
      gene mutations. Furthermore, the differentiation between second line and
      maintenance therapy has not been fully clarified and differs in the clinical
      practice between cancer centers. The authors present a segregation between
      maintenance treatment and second line and present a possible definition for the
      term "maintenance" treatment. In addition, cancer cell evolution induces
      mutations and therefore either targeted therapies or non-specific chemotherapy
      drugs in many patients become ineffective. In the present work pathways such as
      epidermal growth factor, anaplastic lymphoma kinase, met proto-oncogene and PI3K
      are extensively presented and correlated with current chemotherapy treatment.
      Future, perspectives for targeted treatment are presented based on the current
      publications and ongoing clinical trials. 

PMID- 24312148
TI  - Quantitative statistical methods for image quality assessment.
AB  - Quantitative measures of image quality and reliability are critical for both
      qualitative interpretation and quantitative analysis of medical images. While, in
      theory, it is possible to analyze reconstructed images by means of Monte Carlo
      simulations using a large number of noise realizations, the associated
      computational burden makes this approach impractical. Additionally, this approach
      is less meaningful in clinical scenarios, where multiple noise realizations are
      generally unavailable. The practical alternative is to compute closed-form
      analytical expressions for image quality measures. The objective of this paper is
      to review statistical analysis techniques that enable us to compute two key
      metrics: resolution (determined from the local impulse response) and covariance.
      The underlying methods include fixed-point approaches, which compute these
      metrics at a fixed point (the unique and stable solution) independent of the
      iterative algorithm employed, and iteration-based approaches, which yield results
      that are dependent on the algorithm, initialization, and number of iterations. We
      also explore extensions of some of these methods to a range of special contexts,
      including dynamic and motion-compensated image reconstruction. While most of the
      discussed techniques were developed for emission tomography, the general methods
      are extensible to other imaging modalities as well. In addition to enabling image
      characterization, these analysis techniques allow us to control and enhance
      imaging system performance. We review practical applications where performance
      improvement is achieved by applying these ideas to the contexts of both hardware
      (optimizing scanner design) and image reconstruction (designing regularization
      functions that produce uniform resolution or maximize task-specific figures of
      merit). 

PMID- 24312149
TI  - Methodology for quantitative rapid multi-tracer PET tumor characterizations.
AB  - Positron emission tomography (PET) can image a wide variety of functional and
      physiological parameters in vivo using different radiotracers. As more is learned
      about the molecular basis for disease and treatment, the potential value of
      molecular imaging for characterizing and monitoring disease status has increased.
      Characterizing multiple aspects of tumor physiology by imaging multiple PET
      tracers in a single patient provides additional complementary information, and
      there is a significant body of literature supporting the potential value of multi
      tracer PET imaging in oncology. However, imaging multiple PET tracers in a single
      patient presents a number of challenges. A number of techniques are under
      development for rapidly imaging multiple PET tracers in a single scan, where
      signal-recovery processing algorithms are employed to recover various imaging
      endpoints for each tracer. Dynamic imaging is generally used with tracer
      injections staggered in time, and kinetic constraints are utilized to estimate
      each tracers' contribution to the multi-tracer imaging signal. This article
      summarizes past and ongoing work in multi-tracer PET tumor imaging, and then
      organizes and describes the main algorithmic approaches for achieving multi
      tracer PET signal-recovery. While significant advances have been made, the
      complexity of the approach necessitates protocol design, optimization, and
      testing for each particular tracer combination and application. Rapid multi
      tracer PET techniques have great potential for both research and clinical cancer
      imaging applications, and continued research in this area is warranted. 

PMID- 24312150
TI  - Model observers in medical imaging research.
AB  - Model observers play an important role in the optimization and assessment of
      imaging devices. In this review paper, we first discuss the basic concepts of
      model observers, which include the mathematical foundations and psychophysical
      considerations in designing both optimal observers for optimizing imaging systems
      and anthropomorphic observers for modeling human observers. Second, we survey a
      few state-of-the-art computational techniques for estimating model observers and
      the principles of implementing these techniques. Finally, we review a few
      applications of model observers in medical imaging research. 

PMID- 24312151
TI  - Tumor quantification in clinical positron emission tomography.
AB  - Positron emission tomography (PET) is used extensively in clinical oncology for
      tumor detection, staging and therapy response assessment. Quantitative
      measurements of tumor uptake, usually in the form of standardized uptake values
      (SUVs), have enhanced or replaced qualitative interpretation. In this paper we
      review the current status of tumor quantification methods and their applications
      to clinical oncology. Factors that impede quantitative assessment and limit its
      accuracy and reproducibility are summarized, with special emphasis on SUV
      analysis. We describe current efforts to improve the accuracy of tumor uptake
      measurements, characterize overall metabolic tumor burden and heterogeneity of
      tumor uptake, and account for the effects of image noise. We also summarize
      recent developments in PET instrumentation and image reconstruction and their
      impact on tumor quantification. Finally, we offer our assessment of the current
      development needs in PET tumor quantification, including practical techniques for
      fully quantitative, pharmacokinetic measurements. 

PMID- 24312152
TI  - Integrin alpha(v)beta3-targeted radiotracer (99m)Tc-3P-RGD2 useful for
      noninvasive monitoring of breast tumor response to antiangiogenic linifanib
      therapy but not anti-integrin alpha(v)beta3 RGD2 therapy.
AB  - PURPOSE: (99m)Tc-3P-RGD2 is a (99m)Tc-labeled dimeric cyclic RGD peptide that
      binds to integrin alpha(v)beta3 with high affinity and specificity. The purpose
      of this study was to demonstrate the utility of (99m)Tc-3P-RGD2 SPECT/CT (single
      photon emission computed tomography/computed tomography) as a molecular imaging
      tool for noninvasive monitoring breast tumor early response to antiangiogenesis
      therapy with linifanib, and to illustrate its limitations in monitoring the
      efficacy of anti-alpha(v)beta3 treatment. METHODS: To support SPECT/CT imaging,
      biodistribution and therapy studies, the xenografted breast cancer model was
      established by subcutaneous injection of 5 * 106 MDA-MB-435 cells into the fat
      pad of each athymic nude mouse. Linifanib (ABT-869) was used as antiangiogenesis
      agent. The tumor volume was 180 +/- 90 mm3 on the day (-1 day) before baseline
      SPECT/CT. Each animal was treated twice daily with vehicle or 12.5 mg/kg
      linifanib. Longitudinal (99m)Tc-3P-RGD2 SPECT/CT imaging was performed on days 
      1, 1, 4 and 11. Tumors were harvested at each time point for pathological
      analysis of hematoxylin and eosin (H&E) and immunohistochemistry (IHC). Tumor
      uptake of (99m)Tc-3P-RGD2 was calculated from SPECT/CT quantification. When
      cyclic peptide E[c(RGDfK)]2 (RGD2) was used as the anti-alpha(v)beta3 agent,
      SPECT/CT images were obtained only at 7 and 21 days after last RGD2 dose.
      RESULTS: The tumor uptake of (99m)Tc-3P-RGD2 from SPECT/CT quantification was
      almost identical to that from biodistribution. There was a dramatic reduction in
      both %ID and %ID/cm3 tumor uptake of (99m)Tc-3P-RGD2 during the first 24 hours of
      linifanib therapy. The therapeutic effect of linifanib was on both tumor cells
      and vasculature, as determined by IHC analysis of integrin alpha(v)beta3 and
      CD31. Changes in tumor vasculature were further confirmed by pathological H&E
      analysis of tumor tissues. While its %ID tumor uptake increased steadily in
      vehicle-treated group, the %ID tumor uptake of (99m)Tc-3P-RGD2 decreased in
      linifanib-treated group slowly over the 11-day study period. The degree of tumor
      response to linifanib therapy correlated well to the integrin alpha(v)beta3
      expression levels before linifanib therapy. CONCLUSION: (99m)Tc-3P-RGD2 is an
      excellent radiotracer for monitoring integrin alpha(v)beta3 expression during and
      after linifanib therapy. (99m)Tc-3P-RGD2 SPECT/CT is an useful molecular imaging
      tool for patient selection before antiangiogenic and anti-alpha(v)beta3 therapy;
      but it would be difficult to use (99m)Tc-3P-RGD2 for accurate and noninvasive
      monitoring of early tumor response to anti-alpha(v)beta3 therapy.

PMID- 24312153
TI  - Genetically encoded immunophotosensitizer 4D5scFv-miniSOG is a highly selective
      agent for targeted photokilling of tumor cells in vitro.
AB  - Tumor-targeted delivery of cytotoxins presents considerable advantages over their
      passive transport. Chemical conjugation of cytotoxic module to antibody is
      limited due to insufficient reproducibility of synthesis, and recombinant
      immunotoxins are aimed to overcome this disadvantage. We obtained genetically
      encoded immunophotosensitizer 4D5scFv-miniSOG and evaluated its photocytotoxic
      effect in vitro. A single-chain variable fragment (scFv) of humanized 4D5
      antibody was used as a targeting vehicle for selective recognition of the
      extracellular domain of human epidermal growth factor receptor 2 (HER2/neu)
      overexpressed in many human carcinomas. As a phototoxic module we used a recently
      described photoactivated fluorescent flavoprotein miniSOG. We found that
      recombinant protein 4D5scFv-miniSOG exerts a highly specific photo-induced
      cytotoxic effect on HER2/neu-positive human breast adenocarcinoma SK-BR-3 cells
      (IC50= 160 nM). We demonstrated that the 4D5scFv-miniSOG specifically binds to
      HER2-positive cells and internalizes via receptor-mediated endocytosis. Co
      treatment of breast cancer cells with 4D5scFv-miniSOG and Taxol or junction
      opener protein JO-1 produced remarkable additive effects. 

PMID- 24312154
TI  - Establishment of stable reporter expression for in vivo imaging of nuclear factor
      kappaB activation in mouse liver.
AB  - The nuclear factor-kappaB (NF-kappaB) signaling pathway plays a critical role in
      a multitude of cellular processes. Activation of the NF-kappaB transcription
      factor family is essential for the initiation of inflammation, immunity, cell
      proliferation and apoptosis through a list of responsive genes. In hepatic
      tissue, activation of the NF-kappaB pathway has been implicated in a number of
      pathological conditions. Here we described a mouse model for noninvasive
      quantification of NF-kappaB activation in the hepatic tissues. Mice were
      subjected to hydrodynamic delivery with a mixture of pattB-NF-kappaB-Fluc
      reporter and phiC31o integrase vector. Hepatic expression of phiC31o integrase
      mediated chromosomal integration of the pattB-NF-kappaB-Fluc reporter, resulting
      in stable luciferase expression at 300 days post transfection. We applied
      noninvasive imaging and were able to detect NF-kappaB activation under acute
      liver injury and hepatitis conditions. During hepatectomy-induced liver
      regeneration, NF-kappaB activation was detected locally in the tissues at the
      surgery site. Treatment with Sorafenib suppressed NF-kappaB activation,
      accompanied with perturbation of liver regeneration. In conclusion, we
      established a method for stable transfection of the hepatic tissues and applied
      the transfected mice to longitudinal monitoring of NF-kappaB activity under
      pathological conditions. Further exploration of this methodology for
      establishment of other disease models and for evaluation of novel pharmaceuticals
      is likely to be fruitful. 

PMID- 24312155
TI  - Nanodroplet-mediated histotripsy for image-guided targeted ultrasound cell
      ablation.
AB  - This paper is an initial work towards developing an image-guided, targeted
      ultrasound ablation technique by combining histotripsy with nanodroplets that can
      be selectively delivered to tumor cells. Using extremely short, high-pressure
      pulses, histotripsy generates a dense cloud of cavitating microbubbles that
      fractionates tissue. We hypothesize that synthetic nanodroplets that encapsulate
      a perfluoropentane (PFP) core will transition upon exposure to ultrasound pulses
      into gas microbubbles, which will rapidly expand and collapse resulting in
      disruption of cells similar to the histotripsy process but at a significantly
      lower acoustic pressure. The significantly reduced cavitation threshold will
      allow histotripsy to be selectively delivered to the tumor tissue and greatly
      enhance the treatment efficiency while sparing neighboring healthy tissue. To
      test our hypothesis, we prepared nanodroplets with an average diameter of 204 +/-
      4.7 nm at 37 degrees C by self-assembly of an amphiphilic triblock copolymer
      around a PFP core followed by cross-linkage of the polymer shell forming stable
      nanodroplets. The nanodroplets were embedded in agarose tissue phantoms
      containing a sheet of red blood cells (RBCs), which were exposed to 2-cycle
      pulses applied by a 500 kHz focused transducer. Using a high speed camera to
      monitor microbubble generation, the peak negative pressure threshold needed to
      generate bubbles >50 MUm in agarose phantoms containing nanodroplets was measured
      to be 10.8 MPa, which is significantly lower than the 28.8 MPa observed using
      ultrasound pulses alone. High speed images also showed cavitation microbubbles
      produced from the nanodroplets displayed expansion and collapse similar to
      histotripsy alone at higher pressures. Nanodroplet-mediated histotripsy created
      consistent, well-defined fractionation of the RBCs in agarose tissue phantoms at
      10 Hz pulse repetition frequency similar to the lesions generated by histotripsy
      alone but at a significantly lower pressure. These results support our hypothesis
      and demonstrate the potential of using nanodroplet-mediated histotripsy for
      targeted cell ablation.

PMID- 24312157
TI  - Bringing New PET drugs to clinical practice - a regulatory perspective.
AB  - The regulatory framework for radioactive drugs, in particular those used in
      positron emission tomography (PET) scans, has been gradually established since
      the release of the Food and Drug Administration Modernization Act in 1997.
      Various guidances specially tailored to accommodate special properties of PET
      drugs have been issued by the Food and Drug Administration (FDA) in order to
      ensure this valuable technology (i.e., PET molecular imaging) will continue to be
      available to patients and yet the safety and efficacy of PET drugs are well
      regulated so that public health will be protected. This article presents several
      key elements of this regulatory framework for PET drugs. New regulatory avenues
      proposed by the FDA to facilitate the research and development process to bring
      more new PET drugs to clinical practice, as well as to foster the opportunity of
      using "orphan" PET drugs in clinical practice are also discussed in this paper. 

PMID- 24312156
TI  - Molecular imaging of inflammation in atherosclerosis.
AB  - Acute rupture of vulnerable plaques frequently leads to myocardial infarction and
      stroke. Within the last decades, several cellular and molecular players have been
      identified that promote atherosclerotic lesion formation, maturation and plaque
      rupture. It is now widely recognized that inflammation of the vessel wall and
      distinct leukocyte subsets are involved throughout all phases of atherosclerotic
      lesion development. The mechanisms that render a stable plaque unstable and prone
      to rupture, however, remain unknown and the identification of the vulnerable
      plaque remains a major challenge in cardiovascular medicine. Imaging technologies
      used in the clinic offer minimal information about the underlying biology and
      potential risk for rupture. New imaging technologies are therefore being
      developed, and in the preclinical setting have enabled new and dynamic insights
      into the vessel wall for a better understanding of this complex disease.
      Molecular imaging has the potential to track biological processes, such as the
      activity of cellular and molecular biomarkers in vivo and over time. Similarly,
      novel imaging technologies specifically detect effects of therapies that aim to
      stabilize vulnerable plaques and silence vascular inflammation. Here we will
      review the potential of established and new molecular imaging technologies in the
      setting of atherosclerosis, and discuss the cumbersome steps required for
      translating molecular imaging approaches into the clinic. 

PMID- 24312158
TI  - Positron emission tomography imaging of atherosclerosis.
AB  - Atherosclerosis-related cardiovascular events are the leading causes of death in
      the industrialized world. Atherosclerosis develops insidiously and the initial
      manifestation is usually sudden cardiac death, stroke, or myocardial infarction.
      Molecular imaging is a valuable tool to identify the disease at an early stage
      before fatal manifestations occur. Among the various molecular imaging
      techniques, this review mainly focuses on positron emission tomography (PET)
      imaging of atherosclerosis. The targets and pathways that have been investigated
      to date for PET imaging of atherosclerosis include: glycolysis, cell membrane
      metabolism (phosphatidylcholine synthesis), integrin alphavbeta3, low density
      lipoprotein (LDL) receptors (LDLr), natriuretic peptide clearance receptors
      (NPCRs), fatty acid synthesis, vascular cell adhesion molecule-1 (VCAM-1),
      macrophages, platelets, etc. Many PET tracers have been investigated clinically
      for imaging of atherosclerosis. Early diagnosis of atherosclerotic lesions by PET
      imaging can help to prevent the premature death caused by atherosclerosis, and
      smooth translation of promising PET tracers into the clinic is critical to the
      benefit of patients. 

PMID- 24312159
TI  - Cardioprotective C-kit+ bone marrow cells attenuate apoptosis after acute
      myocardial infarction in mice - in-vivo assessment with fluorescence molecular
      imaging.
AB  - Cardiomyocyte loss via apoptosis plays a crucial role in ventricular remodeling
      following myocardial infarction (MI). Cell-based therapy approaches using bone
      marrow derived c-kit+ pluripotent cells may attenuate apoptosis following
      ischemic injury. We therefore thought to examine the early course of apoptosis
      following myocardial infarction - in-vivo - and non-invasively determine the
      effect of c-kit+ bone marrow cells on post-MI remodeling. We studied apoptosis in
      wild-type Kit(+/+) , c-kit mutant Kit(W)/Kit(W-v) and Kit(W)/Kit(W-v) mice after
      cell therapy with bone-marrow derived c-kit+ cells after ischemia-reperfusion
      injury. Mice were followed by hybrid Fluorescence Molecular Tomography/X-ray
      Computed Tomography (FMT-XCT) at 6h, 24h and 7 days after ischemia-reperfusion
      injury using an Annexin V-based fluorescent nanosensor targeting
      phosphatidylserine. Kit(W)/Kit(W-v) mice showed increased and prolonged apoptosis
      compared to control Kit(+/+) mice while c-kit cell therapy was able to attenuate
      the altered apoptosis rates. Increased apoptosis was accompanied by severe
      decline in heart function, determined by cardiac Magnetic Resonance Imaging, and
      cell therapy was able to rescue the animals from deleterious heart failure. Post
      mortem cryoslicing and immunohistochemistry localized the fluorescence signal of
      the Annexin V sensor within the infarcted myocardium. Flow cytometry of digested
      infarct specimens identified apoptotic cardiomyocytes as the major source for the
      in-vivo Annexin V signal. In-vivo molecular imaging using hybrid FMT-XCT reveals
      increased cardiomyocyte apoptosis in Kit(W)/Kit(W-v) mice and shows that c-kit+
      cardioprotective cells are able to attenuate post-MI apoptosis and rescue mice
      from progressive heart failure.

PMID- 24312161
TI  - Applications of Semiconductor Fabrication Methods to Nanomedicine: A Review of
      Recent Inventions and Techniques.
AB  - We live in a world of convergence where scientific techniques from a variety of
      seemingly disparate fields are being applied cohesively to the study and solution
      of biomedical problems. For instance, the semiconductor processing field has been
      primarily developed to cater to the needs of the ever decreasing transistor size
      and cost while increasing functionality of electronic circuits. In recent years,
      pioneers in this field have equipped themselves with a powerful understanding of
      how the same techniques can be applied in the biomedical field to develop new and
      efficient systems for the diagnosis, analysis and treatment of various conditions
      in the human body. In this paper, we review the major inventions and experimental
      methods which have been developed for nano/micro fluidic channels, nanoparticles
      fabricated by top-down methods, and in-vivo nanoporous microcages for effective
      drug delivery. This paper focuses on the information contained in patents as well
      as the corresponding technical publications. The goal of the paper is to help
      emerging scientists understand and improvise over these inventions.

PMID- 24312160
TI  - P2X7 receptor inhibition increases CNTF in the subventricular zone, but not
      neurogenesis or neuroprotection after stroke in adult mice.
AB  - Increasing endogenous ciliary neurotrophic factor (CNTF) expression with a
      pharmacological agent might be beneficial after stroke as CNTF both promotes
      neurogenesis and, separately, is neuroprotective. P2X7 purinergic receptor
      inhibition is neuroprotective in rats and increases CNTF release in rat CMT1A
      Schwann cells. We, first, investigated the role of P2X7 in regulating CNTF and
      neurogenesis in adult mouse subventricular zone (SVZ). CNTF expression was
      increased by daily intravenous injections of the P2X7 antagonist Brilliant Blue G
      (BBG) in naive C57BL/6 or Balb/c mice over 3 days. Despite the ~40-60 % increase
      or decrease in CNTF with BBG or the agonist BzATP, respectively, the number of
      proliferated BrdU+SVZ nuclei did not change. BBG failed to increase FGF2, which
      is involved in CNTF-regulated neurogenesis, but induced IL-6, LIF, and EGF, which
      are known to reduce SVZ proliferation. Injections of IL-6 next to the SVZ induced
      CNTF and FGF2, but not proliferation, suggesting that IL-6 counteracts their
      neurogenesis-inducing effects. Following ischemic injury of the striatum by
      middle cerebral artery occlusion (MCAO), a 3-day BBG treatment increased CNTF in
      the medial penumbra containing the SVZ. BBG also induced CNTF and LIF, which are
      known to be protective following stroke, in the whole striatum after MCAO, but
      not GDNF or BDNF. However, BBG treatment did not reduce the lesion area or
      apoptosis in the penumbra. Even so, this study shows that P2X7 can be targeted
      with systemic drug treatments to differentially regulate neurotrophic factors in
      the brain following stroke. 

PMID- 24312162
TI  - VARIABLE SELECTION FOR SPARSE DIRICHLET-MULTINOMIAL REGRESSION WITH AN
      APPLICATION TO MICROBIOME DATA ANALYSIS.
AB  - With the development of next generation sequencing technology, researchers have
      now been able to study the microbiome composition using direct sequencing, whose
      output are bacterial taxa counts for each microbiome sample. One goal of
      microbiome study is to associate the microbiome composition with environmental
      covariates. We propose to model the taxa counts using a Dirichlet-multinomial
      (DM) regression model in order to account for overdispersion of observed counts.
      The DM regression model can be used for testing the association between taxa
      composition and covariates using the likelihood ratio test. However, when the
      number of the covariates is large, multiple testing can lead to loss of power. To
      deal with the high dimensionality of the problem, we develop a penalized
      likelihood approach to estimate the regression parameters and to select the
      variables by imposing a sparse group [Formula: see text] penalty to encourage
      both group-level and within-group sparsity. Such a variable selection procedure
      can lead to selection of the relevant covariates and their associated bacterial
      taxa. An efficient block-coordinate descent algorithm is developed to solve the
      optimization problem. We present extensive simulations to demonstrate that the
      sparse DM regression can result in better identification of the microbiome
      associated covariates than models that ignore overdispersion or only consider the
      proportions. We demonstrate the power of our method in an analysis of a data set
      evaluating the effects of nutrient intake on human gut microbiome composition.
      Our results have clearly shown that the nutrient intake is strongly associated
      with the human gut microbiome.

PMID- 24312164
TI  - Differentiation without distancing. explaining bi-polarization of opinions
      without negative influence.
AB  - Explanations of opinion bi-polarization hinge on the assumption of negative
      influence, individuals' striving to amplify differences to disliked others.
      However, empirical evidence for negative influence is inconclusive, which
      motivated us to search for an alternative explanation. Here, we demonstrate that
      bi-polarization can be explained without negative influence, drawing on theories
      that emphasize the communication of arguments as central mechanism of influence.
      Due to homophily, actors interact mainly with others whose arguments will
      intensify existing tendencies for or against the issue at stake. We develop an
      agent-based model of this theory and compare its implications to those of
      existing social-influence models, deriving testable hypotheses about the
      conditions of bi-polarization. Hypotheses were tested with a group-discussion
      experiment (N = 96). Results demonstrate that argument exchange can entail bi
      polarization even when there is no negative influence.

PMID- 24312163
TI  - No evidence of association between common autoimmunity STAT4 and IL23R risk
      polymorphisms and non-anterior uveitis.
AB  - OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors
      in autoimmunity. We decided to investigate for the first time the possible role
      of different STAT4/IL23R autoimmune disease-associated polymorphisms on the
      susceptibility to develop non-anterior uveitis and its main clinical phenotypes.
      METHODS: Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and
      rs897200) located within STAT4 gene as well as three independent polymorphisms
      (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using
      TaqMan(r) allelic discrimination in a total of 206 patients with non-anterior
      uveitis and 1553 healthy controls from Spain. RESULTS: No statistically
      significant differences were found when allele and genotype distributions were
      compared between non-anterior uveitis patients and controls for any STAT4
      (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI
      95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22,
      OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08,
      CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965:
      P=0.51, OR=0.93, CI 95%=0.76-1.15). CONCLUSION: Our results do not support a
      relevant role, similar to that described for other autoimmune diseases, of IL23R
      and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition.
      Further studies are needed to discard a possible weak effect of the studied
      variant.

PMID- 24312165
TI  - Impact of HIV-1 backbone on neutralization sensitivity: neutralization profiles
      of heterologous envelope glycoproteins expressed in native subtype C and CRF01_AE
      backbone.
AB  - Standardized assays to assess vaccine and antiviral drug efficacy are critical
      for the development of protective HIV-1 vaccines and drugs. These immune assays
      will be advanced by the development of standardized viral stocks, such as HIV-1
      infectious molecular clones (IMC), that i) express a reporter gene, ii) are
      representative of globally diverse subtypes and iii) are engineered to easily
      exchange envelope (env) genes for expression of sequences of interest. Thus far,
      a subtype B IMC backbone expressing Renilla luciferase (LucR), and into which the
      ectodomain of heterologous env coding sequences can be expressed has been
      successfully developed but as execution of HIV-1 vaccine efficacy trials shifts
      increasingly to non-subtype B epidemics (Southern African and Southeast Asia),
      non-subtype B HIV-1 reagents are needed to support vaccine development. Here we
      describe two IMCs derived from subtypes C and CRF01_AE HIV-1 primary isolates
      expressing LucR (IMC.LucR) that were engineered to express heterologous gp160
      Envs. 18 constructs expressing various subtypes C and CRF01_AE Envs, mostly
      acute, in subtype-matched and -unmatched HIV backbones were tested for
      functionality and neutralization sensitivity. Our results suggest a possible
      effect of non-env HIV-1 genes on the interaction of Env and neutralizing
      antibodies and highlight the need to generate a library of IMCs representative of
      the HIV-1 subtype spectrum to be used as standardized neutralization assay
      reagents for assessing HIV-1 vaccine efficacy. 

PMID- 24312166
TI  - Neural correlates of emotional personality: a structural and functional magnetic
      resonance imaging study.
AB  - Studies addressing brain correlates of emotional personality have remained
      sparse, despite the involvement of emotional personality in health and well
      being. This study investigates structural and functional brain correlates of
      psychological and physiological measures related to emotional personality.
      Psychological measures included neuroticism, extraversion, and agreeableness
      scores, as assessed using a standard personality questionnaire. As a
      physiological measure we used a cardiac amplitude signature, the so-called E
      kappa value (computed from the electrocardiogram) which has previously been
      related to tender emotionality. Questionnaire scores and E kappa values were
      related to both functional (eigenvector centrality mapping, ECM) and structural
      (voxel-based morphometry, VBM) neuroimaging data. Functional magnetic resonance
      imaging (fMRI) data were obtained from 22 individuals (12 females) while
      listening to music (joy, fear, or neutral music). ECM results showed that
      agreeableness scores correlated with centrality values in the dorsolateral
      prefrontal cortex, the anterior cingulate cortex, and the ventral striatum
      (nucleus accumbens). Individuals with higher E kappa values (indexing higher
      tender emotionality) showed higher centrality values in the subiculum of the
      right hippocampal formation. Structural MRI data from an independent sample of 59
      individuals (34 females) showed that neuroticism scores correlated with volume of
      the left amygdaloid complex. In addition, individuals with higher E kappa showed
      larger gray matter volume in the same portion of the subiculum in which
      individuals with higher E kappa showed higher centrality values. Our results
      highlight a role of the amygdala in neuroticism. Moreover, they indicate that a
      cardiac signature related to emotionality (E kappa) correlates with both function
      (increased network centrality) and structure (grey matter volume) of the
      subiculum of the hippocampal formation, suggesting a role of the hippocampal
      formation for emotional personality. Results are the first to show personality
      related differences using eigenvector centrality mapping, and the first to show
      structural brain differences for a physiological measure associated with
      personality. 

PMID- 24312167
TI  - Reverse engineering the cooperative machinery of human hemoglobin.
AB  - Hemoglobin transports molecular oxygen from the lungs to all human tissues for
      cellular respiration. Its alpha2beta2 tetrameric assembly undergoes cooperative
      binding and releasing of oxygen for superior efficiency and responsiveness. Over
      past decades, hundreds of hemoglobin structures were determined under a wide
      range of conditions for investigation of molecular mechanism of cooperativity.
      Based on a joint analysis of hemoglobin structures in the Protein Data Bank (Ren,
      companion article), here I present a reverse engineering approach to elucidate
      how two subunits within each dimer reciprocate identical motions that achieves
      intradimer cooperativity, how ligand-induced structural signals from two subunits
      are integrated to drive quaternary rotation, and how the structural environment
      at the oxygen binding sites alter their binding affinity. This mechanical model
      reveals the intricate design that achieves the cooperative mechanism and has
      previously been masked by inconsistent structural fluctuations. A number of
      competing theories on hemoglobin cooperativity and broader protein allostery are
      reconciled and unified. 

PMID- 24312169
TI  - HIV-1 Tat interacts with and regulates the localization and processing of amyloid
      precursor protein.
AB  - HIV-1 Tat protein plays various roles in virus proliferation and in the
      regulation of numerous host cell functions. Accumulating evidence suggests that
      HIV-1 Tat also plays an important role in HIV-associated neurocognitive disorders
      (HAND) by disrupting intracellular communication. Amyloid beta (Abeta) is
      generated from amyloid precursor protein (APP) and accumulates in the senile
      plaques of Alzheimer's disease patients. This study demonstrates that Tat
      interacts with APP both in vitro and in vivo, and increases the level of Abeta42
      by recruiting APP into lipid rafts. Co-localization of Tat with APP in the
      cytosol was observed in U-87 MG cells that expressed high levels of Tat, and
      redistribution of APP into lipid rafts, a site of increased beta- and gamma
      secretase activity, was demonstrated by discontinuous sucrose density gradient
      ultracentrifugation in the presence of Tat. Furthermore, Tat enhanced the
      cleavage of APP by beta-secretase in vitro, resulting in 5.5-fold higher levels
      of Abeta42. This was consistent with increased levels of beta-C-terminal fragment
      (beta-CTF) and reduced levels of alpha-CTF. Moreover, stereotaxic injection of a
      lentiviral Tat expression construct into the hippocampus of APP/presenilin-1
      (PS1) transgenic mice resulted in increased Tat-mediated production and
      processing of Abeta in vivo. Increased levels of Abeta42, as well as an increase
      in the number and size of Abeta plaques, were observed in the hippocampus
      following injection of Tat virus compared with mock virus. These results suggest
      that HIV-1 Tat may contribute to HAND by interacting with and modifying APP
      processing, thereby increasing Abeta production. 

PMID- 24312170
TI  - Dose-response relationship of physical activity to premature and total all-cause
      and cardiovascular disease mortality in walkers.
AB  - PURPOSE: To assess the dose-response relationships between cause-specific
      mortality and exercise energy expenditure in a prospective epidemiological cohort
      of walkers. METHODS: The sample consisted of the 8,436 male and 33,586 female
      participants of the National Walkers' Health Study. Walking energy expenditure
      was calculated in metabolic equivalents (METs, 1 MET = 3.5 ml O2/kg/min), which
      were used to divide the cohort into four exercise categories: category 1 (<= 1.07
      MET-hours/d), category 2 (1.07 to 1.8 MET-hours/d), category 3 (1.8 to 3.6 MET
      hours/d), and category 4 (>= 3.6 MET-hours/d). Competing risk regression analyses
      were use to calculate the risk of mortality for categories 2, 3 and 4 relative to
      category 1. RESULTS: 22.9% of the subjects were in category 1, 16.1% in category
      2, 33.3% in category 3, and 27.7% in category 4. There were 2,448 deaths during
      the 9.6 average years of follow-up. Total mortality was 11.2% lower in category 2
      (P = 0.04), 32.4% lower in category 3 (P<10(-12)) and 32.9% lower in category 4
      (P = 10(-11)) than in category 1. For underlying causes of death, the respective
      risk reductions for categories 2, 3 and 4 were 23.6% (P = 0.008), 35.2% (P<10(
      5)), and 34.9% (P = 0.0001) for cardiovascular disease mortality; 27.8% (P =
      0.18), 20.6% (P = 0.07), and 31.4% (P = 0.009) for ischemic heart disease
      mortality; and 39.4% (P = 0.18), 63.8% (P = 0.005), and 90.6% (P = 0.002) for
      diabetes mortality when compared to category 1. For all related mortality (i.e.,
      underlying and contributing causes of death combined), the respective risk
      reductions for categories 2, 3 and 4 were 18.7% (P = 0.22), 42.5% (P = 0.001),
      and 57.5% (P = 0.0001) for heart failure; 9.4% (P = 0.56), 44.3% (P = 0.0004),
      and 33.5% (P = 0.02) for hypertensive diseases; 11.5% (P = 0.38), 41.0% (P<10(
      4)), and 35.5% (P = 0.001) for dysrhythmias: and 23.2% (P = 0.13), 45.8% (P =
      0.0002), and 41.1% (P = 0.005) for cerebrovascular diseases when compared to
      category 1. CONCLUSIONS: There are substantial health benefits to exceeding the
      current exercise guidelines.

PMID- 24312168
TI  - Detection of HIV-1 neutralizing antibodies in a human CD4+/CXCR4+/CCR5+ T
      lymphoblastoid cell assay system.
AB  - Sensitive assays are needed to meaningfully assess low levels of neutralizing
      antibodies (NAbs) that may be important for protection against the acquisition of
      HIV-1 infection in vaccine recipients. The current assay of choice uses a non
      lymphoid cell line (TZM-bl) that may lack sensitivity owing to over expression of
      CD4 and CCR5. We used transfection of a human CD4+/CXCR4+/alpha4beta7+ T
      lymphoblastoid cell line (A3.01) with a CMV IE promoter-driven CCR5neo vector to
      stably express CCR5. The resulting line, designated A3R5, is permissive to a wide
      range of CCR5-tropic circulating strains of HIV-1, including HIV-1 molecular
      clones containing a Tat-inducible Renilla luciferase reporter gene and expressing
      multiple Env subtypes. Flow cytometric analysis found CCR5 surface expression on
      A3R5 cells to be markedly less than TZM-bl but similar to CD3.8 stimulated PBMC.
      More importantly, neutralization mediated by a diverse panel of monoclonal
      antibodies, HIV-1 positive polyclonal sera and sCD4 was consistently greater in
      A3R5 compared to TZM-bl cells. The A3R5 cell line provides a novel approach to
      guide the development and qualification of promising new HIV-1 vaccine
      immunogens. 

PMID- 24312171
TI  - Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one
      additional mode of action.
AB  - Bacterial enoyl-acyl carrier protein reductase (FabI) is a promising novel
      antibacterial target. We isolated a new class of FabI inhibitor from Penicillium
      chrysogenum, which produces various antibiotics, the mechanisms of some of them
      are unknown. The isolated FabI inhibitor was determined to be meleagrin by mass
      spectroscopy and nuclear magnetic resonance spectral analyses, and its more
      active and inactive derivatives were chemically prepared. Consistent with their
      selective inhibition of Staphylococcus aureus FabI, meleagrin and its more active
      derivatives directly bound to S. aureus FabI in a fluorescence quenching assay,
      inhibited intracellular fatty acid biosynthesis and growth of S. aureus, and
      increased the minimum inhibitory concentration for fabI-overexpressing S. aureus.
      The compounds that were not effective against the FabK isoform, however,
      inhibited the growth of Streptococcus pneumoniae that contained only the FabK
      isoform. Additionally no resistant mutant to the compounds was obtained.
      Importantly, fabK-overexpressing Escherichia coli was not resistant to these
      compounds, but was resistant to triclosan. These results demonstrate that the
      compounds inhibited another target in addition to FabI. Thus, meleagrin is a new
      class of FabI inhibitor with at least one additional mode of action that could
      have potential for treating multidrug-resistant bacteria. 

PMID- 24312172
TI  - Adaptive sampling of information in perceptual decision-making.
AB  - In many perceptual and cognitive decision-making problems, humans sample multiple
      noisy information sources serially, and integrate the sampled information to make
      an overall decision. We derive the optimal decision procedure for two-alternative
      choice tasks in which the different options are sampled one at a time, sources
      vary in the quality of the information they provide, and the available time is
      fixed. To maximize accuracy, the optimal observer allocates time to sampling
      different information sources in proportion to their noise levels. We tested
      human observers in a corresponding perceptual decision-making task. Observers
      compared the direction of two random dot motion patterns that were triggered only
      when fixated. Observers allocated more time to the noisier pattern, in a manner
      that correlated with their sensory uncertainty about the direction of the
      patterns. There were several differences between the optimal observer predictions
      and human behaviour. These differences point to a number of other factors, beyond
      the quality of the currently available sources of information, that influences
      the sampling strategy. 

PMID- 24312173
TI  - Evolution of the thermopsin peptidase family (A5).
AB  - Thermopsin is a peptidase from Sulfolobus acidocaldarius that is active at low pH
      and high temperature. From reversible inhibition with pepstatin, thermopsin is
      thought to be an aspartic peptidase. It is a member of the only family of
      peptidases to be restricted entirely to the archaea, namely peptidase family A5.
      Evolution within this family has been mapped, using a taxonomic tree based on the
      known classification of archaea. Homologues are found only in archaeans that are
      both hyperthermophiles and acidophiles, and this implies lateral transfer of
      genes between archaea, because species with homologues are not necessarily
      closely related. Despite the remarkable stability and activity in extreme
      conditions, no tertiary structure has been solved for any member of the family,
      and the catalytic mechanism is unknown. Putative catalytic residues have been
      predicted here by examination of aligned sequences. 

PMID- 24312174
TI  - Is the improvement of CF patients, hospitalized for pulmonary exacerbation,
      correlated to a decrease in bacterial load?
AB  - BACKGROUND: Cystic Fibrosis (CF) patients are vulnerable to airway colonization
      with Pseudomonas aeruginosa. In case eradication fails after antibiotic
      treatment, patients become chronically colonized with P. aeruginosa, with
      recurrent pulmonary exacerbation, for which patients typically are hospitalized
      for 2 weeks and receive intravenous antibiotic treatment. Normally, improvement
      of the patients' health is established. AIM: Determination of the correspondence
      between patient improvement and changes of the P. aeruginosa and total bacterial
      load in the sputum. METHODS: Eighteen CF patients with exacerbation were included
      for a total of 27 hospitalization episodes. At day 1, 8 and 15, inflammation and
      lung function parameters were determined, together with the P. aeruginosa load in
      the sputum using culture, quantitative PCR (qPCR) and propidium monoazide qPCR.
      RESULTS: Patients improved during hospitalization (decrease in levels of C
      reactive protein, white blood cell counts and erythrocyte sedimentation rate,
      increase of FEV1), reaching normal values already after one week. Also the P.
      aeruginosa load and the total bacterial load decreased during the first week of
      antibiotic treatment (p<0.05), except for patients with a low lung function
      (FEV1<=39.4%), for whom no significant decrease of P. aeruginosa was established.
      Comparison of culture-based and propidium monoazide qPCR-based quantification of
      P. aeruginosa showed that at the end of the treatment on average 62% of the P.
      aeruginosa cells are not cultivable, indicating that many cells are alive but
      dormant, or dead but still structurally intact. CONCLUSION: Improvement of the
      clinical status is accompanied with a decrease of the P. aeruginosa load, whereby
      both occur mainly during the first week of antibiotic treatment. However, for
      patients with a low lung function, no decrease of the P. aeruginosa load is
      observed. Comparison of detection techniques shows that a large amount of
      noncultivable or dead bacteria are present in the samples.

PMID- 24312175
TI  - Functional characteristics of the naked mole rat MU-opioid receptor.
AB  - While humans and most animals respond to u-opioid receptor (MOR) agonists with
      analgesia and decreased aggression, in the naked mole rat (NMR) opioids induce
      hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human
      mu-opioid receptor gene (OPRM1) can underlie altered behavioral responses to
      opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may
      differ from other species. Sequencing of the NMR oprm1 revealed strong homology
      to other mammals, but exposed three unique amino acids that might affect receptor
      ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian
      expression vectors and transfected into HEK293 cells. Radioligand binding and 3'
      5'-cyclic adenosine monophosphate (cAMP) enzyme immunoassays were used to compare
      opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor
      protein levels we detected significantly lower [3H]DAMGO binding to NMR compared
      to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition.
      Strong DAMGO-induced MOR internalization was detectable using radioligand binding
      and confocal imaging in HEK293 cells expressing rat or NMR receptor, while
      morphine showed weak or no effects. In summary, we found minor functional
      differences between rat and NMR MOR suggesting that other differences e.g. in
      anatomical distribution of MOR underlie the NMR's extreme reaction to opioids.

PMID- 24312176
TI  - Genetic association study between STK39 and CCDC62/HIP1R and Parkinson's disease.
AB  - BACKGROUND: The first large-scale meta-analysis of published genome-wide
      association studies (GWAS) in Parkinson's disease (PD) identified 5 new genetic
      loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). Very recently, a large
      scale replication and heterogeneity study also reported that STK39 and
      CCDC62/HIP1R increased risk of PD in Asian and Caucasian populations. However,
      their roles still remain unclear in a Han Chinese population from mainland China.
      METHODS: We examined genetic associations of STK39 rs2102808 and CCDC62/HIP1R
      rs12817488 with PD susceptibility in a Han Chinese population of 783 PD patients
      and 725 controls. We also performed further stratified analyses by the age of
      onset and accomplished in-depth clinical characteristics analyses between the
      different genotypes for each locus. RESULTS: No significant differences were
      observed in the minor allele frequency (MAF) among cases and controls at the two
      loci (STK39 rs2102808: OR = 1.06, 95% CI = 0.91, 1.23, P = 0.467; CCDC62/HIP1R
      rs12817488: OR = 0.88, 95% CI = 0.76, 1.01, P = 0.072). Subgroup analyses by the
      age of onset also showed no significant differences among different subgroups of
      the two loci. In addition, minor allele carriers cannot be distinguished from non
      carriers based on their clinical features at the two loci. CONCLUSIONS: We are
      unable to demonstrate the association between STK39 and CCDC62/HIP1R and PD
      susceptibility in a Han Chinese population from mainland China. Additional
      replication studies in other populations and functional studies are warranted to
      better validate the role of the two new loci in PD risk.

PMID- 24312177
TI  - Identification of traditional medicinal plant extracts with novel anti-influenza
      activity.
AB  - The emergence of drug resistant variants of the influenza virus has led to a need
      to identify novel and effective antiviral agents. As an alternative to synthetic
      drugs, the consolidation of empirical knowledge with ethnopharmacological
      evidence of medicinal plants offers a novel platform for the development of
      antiviral drugs. The aim of this study was to identify plant extracts with proven
      activity against the influenza virus. Extracts of fifty medicinal plants,
      originating from the tropical rainforests of Borneo used as herbal medicines by
      traditional healers to treat flu-like symptoms, were tested against the H1N1 and
      H3N1 subtypes of the virus. In the initial phase, in vitro micro-inhibition
      assays along with cytotoxicity screening were performed on MDCK cells. Most plant
      extracts were found to be minimally cytotoxic, indicating that the compounds
      linked to an ethnomedical framework were relatively innocuous, and eleven crude
      extracts exhibited viral inhibition against both the strains. All extracts
      inhibited the enzymatic activity of viral neuraminidase and four extracts were
      also shown to act through the hemagglutination inhibition (HI) pathway. Moreover,
      the samples that acted through both HI and neuraminidase inhibition (NI)
      evidenced more than 90% reduction in virus adsorption and penetration, thereby
      indicating potent action in the early stages of viral replication. Concurrent
      studies involving Receptor Destroying Enzyme treatments of HI extracts indicated
      the presence of sialic acid-like component(s) that could be responsible for
      hemagglutination inhibition. The manifestation of both modes of viral inhibition
      in a single extract suggests that there may be a synergistic effect implicating
      more than one active component. Overall, our results provide substantive support
      for the use of Borneo traditional plants as promising sources of novel anti
      influenza drug candidates. Furthermore, the pathways involving inhibition of
      hemagglutination could be a solution to the global occurrence of viral strains
      resistant to neuraminidase drugs. 

PMID- 24312178
TI  - A randomized cross-over trial of the postprandial effects of three different
      diets in patients with type 2 diabetes.
AB  - BACKGROUND: In the clinic setting both fasting levels of glucose and the area
      under the curve (AUC) of glucose, by determination of HbA1c levels, are used for
      risk assessments, in type 2 diabetes (NIDDM). However little is known about
      postprandial levels, and hence AUC, regarding other traditional risk factors such
      as insulin and blood-lipids and how this is affected by different diets.
      OBJECTIVE: To study postprandial effects of three diets, during a single day, in
      NIDDM. METHODS: A low-fat diet (45-56 energy-% from carbohydrates), and a low
      carbohydrate diet (16-24 energy-% from carbohydrates) was compared with a
      Mediterranean-style diet (black coffee for breakfast and the same total-caloric
      intake as the other two diets for lunch with red wine, 32-35 energy-% from
      carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day
      at the clinic from food was 1025-1080 kCal in men and 905-984 kCal in women. The
      test meals were consumed at a diabetes ward under supervision. RESULTS: Twenty
      one participants were recruited and 19 completed the studies. The low
      carbohydrate diet induced lower insulin and glucose excursions compared with the
      low-fat diet (p<0.0005 for both AUC). The insulin-response following the single
      Mediterranean-style lunch-meal was more pronounced than during the low-fat diet
      lunch (insulin increase-ratio of the low-fat diet: 4.35 +/- 2.2, of Mediterranean
      style diet: 8.12 +/- 5.2, p = 0.001) while postprandial glucose levels were
      similar. The increase-ratio of insulin correlated with the elevation of the
      incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean
      style diet lunch (Spearman, r = 0.64, p = 0.003). CONCLUSIONS: The large
      Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as
      the low-fat meal despite almost double amount of calories due to a pronounced
      insulin-increase. This suggests that accumulation of caloric intake from
      breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM
      might be advantageous from a metabolic perspective. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01522157 NCT01522157.

PMID- 24312179
TI  - A reassessment of the relationship between GDP and life satisfaction.
AB  - The scientific debate on the relation between Gross Domestic Product (GDP) and
      self reported indices of life satisfaction is still open. In a well-known
      finding, Easterlin reported no significant relationship between happiness and
      aggregate income in time-series analysis. However, life satisfaction appears to
      be strictly monotonically increasing with income when one studies this relation
      at a point in time across nations. Here, we analyze the relation between per
      capita GDP and life satisfaction without imposing a functional form and
      eliminating potentially confounding country-specific factors. We show that this
      relation clearly increases in country with a per capita GDP below 15,000 USD
      (2005 in Purchasing Power Parity), then it flattens for richer countries. The
      probability of reporting the highest level of life satisfaction is more than 12%
      lower in the poor countries with a per capita GDP below 5,600 USD than in the
      counties with a per capita GDP of about 15,000 USD. In countries with an income
      above 17,000 USD the probability of reporting the highest level of life
      satisfaction changes within a range of 2% maximum. Interestingly enough, life
      satisfaction seems to peak at around 30,000 USD and then slightly but
      significantly decline among the richest countries. These results suggest an
      explanation of the Easterlin paradox: life satisfaction increases with GDP in
      poor country, but this relation is approximately flat in richer countries. We
      explain this relation with aspiration levels. We assume that a gap between
      aspiration and realized income is negatively perceived; and aspirations to higher
      income increase with income. These facts together have a negative effect on life
      satisfaction, opposite to the positive direct effect of the income. The net
      effect is ambiguous. We predict a higher negative effect in individuals with
      higher sensitivity to losses (measured by their neuroticism score) and provide
      econometric support of this explanation. 

PMID- 24312180
TI  - Impact of a labour disruption affecting local public health on the incidence of
      chlamydia infections in Toronto.
AB  - INTRODUCTION: Labour disruptions that interrupt services can be a natural
      experiment to examine the effect of halting a program. A five-week municipal
      labour disruption in Toronto during the summer of 2009 provided an opportunity to
      investigate the impact of reduced sexual health services. METHODS: We examined
      the incidence of reported chlamydia in Toronto during the five years (2004-2008)
      preceding the labour disruption and during the periods just before, during, and
      after the labour disruption. Comparisons of actual reports for 2009 were made to
      immediately adjacent periods around the labour disruption, to historical trends
      and to forecasted rates. Interrupted time series analysis was used to test for
      significant differences in the trend of reported chlamydia incidence. RESULTS:
      There was no significant difference in the trend of reported chlamydia incidence
      around the time of the strike. However, there was a small but significant
      increase in the incidence of reported chlamydia, particularly among females under
      25 years old immediately following the labour disruption. The reported incidence
      for this group was higher than would be expected based on annual increases and
      projected seasonal trends. CONCLUSIONS: There was a small increase in incidence
      of reported cases of chlamydia for certain groups that went beyond what is
      expected during the time immediately following the labour disruption. While
      causation cannot be implied from our ecological study, public health services may
      play a role in the control of sexually transmitted infections, even in the short
      term. This underscores the need for future work to understand whether the changes
      observed can be attributed to the absence of these services.

PMID- 24312181
TI  - More tweets, more votes: social media as a quantitative indicator of political
      behavior.
AB  - Is social media a valid indicator of political behavior? There is considerable
      debate about the validity of data extracted from social media for studying
      offline behavior. To address this issue, we show that there is a statistically
      significant association between tweets that mention a candidate for the U.S.
      House of Representatives and his or her subsequent electoral performance. We
      demonstrate this result with an analysis of 542,969 tweets mentioning candidates
      selected from a random sample of 3,570,054,618, as well as Federal Election
      Commission data from 795 competitive races in the 2010 and 2012 U.S.
      congressional elections. This finding persists even when controlling for
      incumbency, district partisanship, media coverage of the race, time, and
      demographic variables such as the district's racial and gender composition. Our
      findings show that reliable data about political behavior can be extracted from
      social media. 

PMID- 24312182
TI  - Use of the gamma-H2AX assay to investigate DNA repair dynamics following multiple
      radiation exposures.
AB  - Radiation therapy is one of the most common and effective strategies used to
      treat cancer. The irradiation is usually performed with a fractionated scheme,
      where the dose required to kill tumour cells is given in several sessions, spaced
      by specific time intervals, to allow healthy tissue recovery. In this work, we
      examined the DNA repair dynamics of cells exposed to radiation delivered in
      fractions, by assessing the response of histone-2AX (H2AX) phosphorylation (gamma
      H2AX), a marker of DNA double strand breaks. gamma-H2AX foci induction and
      disappearance were monitored following split dose irradiation experiments in
      which time interval between exposure and dose were varied. Experimental data have
      been coupled to an analytical theoretical model, in order to quantify key
      parameters involved in the foci induction process. Induction of gamma-H2AX foci
      was found to be affected by the initial radiation exposure with a smaller number
      of foci induced by subsequent exposures. This was compared to chromatin
      relaxation and cell survival. The time needed for full recovery of gamma-H2AX
      foci induction was quantified (12 hours) and the 1:1 relationship between
      radiation induced DNA double strand breaks and foci numbers was critically
      assessed in the multiple irradiation scenarios. 

PMID- 24312183
TI  - Analysis of post-deployment cognitive performance and symptom recovery in U.S.
      Marines.
AB  - BACKGROUND: Computerized neurocognitive testing (NCAT) has been proposed to be
      useful as a screening tool for post-deployment cognitive deficits in the setting
      of mild traumatic brain injury (mTBI). We assessed the clinical utility of post
      injury/post-deployment Automated Neurocognitive Assessment Metric (ANAM) testing,
      using a longitudinal design to compare baseline ANAM tests with two post
      deployment ANAM tests in a group of Marines who experienced combat during
      deployment. METHODS AND FINDINGS: Post-deployment cognitive performance and
      symptom recovery were compared in a subsample of 1324 U.S. Marines with high
      rates of combat exposure during deployment. Of the sample, 169 Marines had
      available baseline and twice repeated post-deployment ANAM results. A
      retrospective analysis of the ANAM data, which consisted of a self-report
      questionnaire about deployment-related blast exposure, recent history of mTBI,
      current clinical symptoms, and cognitive performance. Self-reported concussion
      sustained anytime during deployment was associated with a decrease in cognitive
      performance measured between 2-8 weeks post-deployment. At the second post
      deployment test conducted on average eight months later, performance on the
      second simple reaction time test, in particular, remained impaired and was the
      most consistent and sensitive indicator of the cognitive decrements.
      Additionally, post-concussive symptoms were shown to persist in injured Marines
      with a self-reported history of concussion for an additional five months after
      most cognitive deficits resolved. Results of this study showed a measurable
      deployment effect on cognitive performance, although this effect appears to
      resolve without lasting clinical sequelae in those without history of deployment
      related concussion. CONCLUSIONS: These results highlight the need for a detailed
      clinical examination for service members with history of concussion and
      persistent clinical symptoms. Reliance solely upon computerized neurocognitive
      testing as a method for identifying service members requiring clinical follow-up
      post-concussion is not recommended, as cognitive functioning only slowly returned
      to baseline levels in the setting of persistent clinical symptoms.

PMID- 24312184
TI  - Gorilla mothers also matter! New insights on social transmission in gorillas
      (Gorilla gorilla gorilla) in captivity.
AB  - The present paper describes two distinct behaviors relating to food processing
      and communication that were observed in a community of five separately housed
      groups of lowland gorillas (Gorilla gorilla gorilla) in captivity during two
      study periods one decade apart: (1) a food processing technique to separate wheat
      from chaff, the so-called puff-blowing technique; and (2) a male display used to
      attract the attention of visitors, the so-called throw-kiss-display. We
      investigated (a) whether the behaviors were transmitted within the respective
      groups; and if yes, (b) their possible mode of transmission. Our results showed
      that only the food processing technique spread from three to twenty-one
      individuals during the ten-year period, whereas the communicative display died
      out completely. The main transmission mode of the puff-blowing technique was the
      mother-offspring dyad: offspring of puff-blowing mothers showed the behavior,
      while the offspring of non- puff-blowing mothers did not. These results strongly
      support the role mothers play in the acquisition of novel skills and vertical
      social transmission. Furthermore, they suggest that behaviors, which provide a
      direct benefit to individuals, have a high chance of social transmission while
      the loss of benefits can result in the extinction of behaviors. 

PMID- 24312185
TI  - Will an unsupervised self-testing strategy for HIV work in health care workers of
      South Africa? A cross sectional pilot feasibility study.
AB  - BACKGROUND: In South Africa, stigma, discrimination, social visibility and fear
      of loss of confidentiality impede health facility-based HIV testing. With 50% of
      adults having ever tested for HIV in their lifetime, private, alternative testing
      options are urgently needed. Non-invasive, oral self-tests offer a potential for
      a confidential, unsupervised HIV self-testing option, but global data are
      limited. METHODS: A pilot cross-sectional study was conducted from January to
      June 2012 in health care workers based at the University of Cape Town, South
      Africa. An innovative, unsupervised, self-testing strategy was evaluated for
      feasibility; defined as completion of self-testing process (i.e., self test
      conduct, interpretation and linkage). An oral point-of-care HIV test, an Internet
      and paper-based self-test HIV applications, and mobile phones were synergized to
      create an unsupervised strategy. Self-tests were additionally confirmed with
      rapid tests on site and laboratory tests. Of 270 health care workers (18 years
      and above, of unknown HIV status approached), 251 consented for participation.
      FINDINGS: Overall, about 91% participants rated a positive experience with the
      strategy. Of 251 participants, 126 evaluated the Internet and 125 the paper-based
      application successfully; completion rate of 99.2%. All sero-positives were
      linked to treatment (completion rate:100% (95% CI, 66.0-100). About half of sero
      negatives were offered counselling on mobile phones; completion rate: 44.6% (95%
      CI, 38.0-51.0). A majority of participants (78.1%) were females, aged 18-24 years
      (61.4%). Nine participants were found sero-positive after confirmatory tests
      (prevalence 3.6% 95% CI, 1.8-6.9). Six of nine positive self-tests were
      accurately interpreted; sensitivity: 66.7% (95% CI, 30.9-91.0); specificity:100%
      (95% CI, 98.1-100). INTERPRETATION: Our unsupervised self-testing strategy was
      feasible to operationalize in health care workers in South Africa. Linkages were
      successfully operationalized with mobile phones in all sero-positives and about
      half of the sero-negatives sought post-test counselling. Controlled trials and
      implementation research studies are needed before a scale-up is considered.

PMID- 24312186
TI  - Tactile modulation of whisking via the brainstem loop: statechart modeling and
      experimental validation.
AB  - Rats repeatedly sweep their facial whiskers back and forth in order to explore
      their environment. Such explorative whisking appears to be driven by central
      pattern generators (CPGs) that operate independently of direct sensory feedback.
      Nevertheless, whisking can be modulated by sensory feedback, and it has been
      hypothesized that some of this modulation already occurs within the brainstem.
      However, the interaction between sensory feedback and CPG activity is poorly
      understood. Using the visual language of statecharts, a dynamic, bottom-up
      computerized model of the brainstem loop of the whisking system was built in
      order to investigate the interaction between sensory feedback and CPG activity
      during whisking behavior. As a benchmark, we used a previously quantified closed
      loop phenomenon of the whisking system, touched-induced pump (TIP), which is
      thought to be mediated by the brainstem loop. First, we showed that TIPs depend
      on sensory feedback, by comparing TIP occurrence in intact rats with that in rats
      whose sensory nerve was experimentally cut. We then inspected several possible
      feedback mechanisms of TIPs using our model. The model ruled out all hypothesized
      mechanisms but one, which adequately simulated the corresponding motion observed
      in the rat. Results of the simulations suggest that TIPs are generated via
      sensory feedback that activates extrinsic retractor muscles in the mystacial pad.
      The model further predicted that in addition to the touching whisker, all
      whiskers found on the same side of the snout should exhibit a TIP. We present
      experimental results that confirm the predicted movements in behaving rats,
      establishing the validity of the hypothesized interaction between sensory
      feedback and CPG activity we suggest here for the generation of TIPs in the
      whisking system. 

PMID- 24312189
TI  - An approach for the accurate measurement of social morality levels.
AB  - In the social sciences, computer-based modeling has become an increasingly
      important tool receiving widespread attention. However, the derivation of the
      quantitative relationships linking individual moral behavior and social morality
      levels, so as to provide a useful basis for social policy-making, remains a
      challenge in the scholarly literature today. A quantitative measurement of
      morality from the perspective of complexity science constitutes an innovative
      attempt. Based on the NetLogo platform, this article examines the effect of
      various factors on social morality levels, using agents modeling moral behavior,
      immoral behavior, and a range of environmental social resources. Threshold values
      for the various parameters are obtained through sensitivity analysis; and
      practical solutions are proposed for reversing declines in social morality
      levels. The results show that: (1) Population size may accelerate or impede the
      speed with which immoral behavior comes to determine the overall level of social
      morality, but it has no effect on the level of social morality itself; (2) The
      impact of rewards and punishment on social morality levels follows the "5?1
      rewards-to-punishment rule," which is to say that 5 units of rewards have the
      same effect as 1 unit of punishment; (3) The abundance of public resources is
      inversely related to the level of social morality; (4) When the cost of
      population mobility reaches 10% of the total energy level, immoral behavior
      begins to be suppressed (i.e. the 1/10 moral cost rule). The research approach
      and methods presented in this paper successfully address the difficulties
      involved in measuring social morality levels, and promise extensive application
      potentials. 

PMID- 24312188
TI  - Dietary chemoprevention of PhIP induced carcinogenesis in male Fischer 344 rats
      with tomato and broccoli.
AB  - The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP),
      found in meats cooked at high temperatures, has been implicated in
      epidemiological and rodent studies for causing breast, prostate, and colorectal
      cancers. A previous animal study using a xenograft model has shown that whole
      tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor
      reduction compared to when eaten alone. Our aim was to determine if PhIP-induced
      carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli
      powders. Male Fischer 344 rats (n = 45) were randomized into the following
      treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the
      first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet
      at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks).
      Study animals were monitored for 52 weeks and were euthanized as necessary based
      on a set of criteria for health status and tumor burden. Although there appeared
      to be some hepatic and intestinal toxicity due to the combination of PhIP and
      tomato + broccoli, these rodents had improved survival and reduced incidence
      and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone
      treated group. Rats eating tomato + broccoli exhibited a marked decrease in the
      number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in
      situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal
      adenocarcinomas and skin carcinomas. Although the apparent toxic effects of
      combined PhIP and tomato + broccoli need additional study, the results of this
      study support the hypothesis that a diet rich in tomato and broccoli can reduce
      or prevent dietary carcinogen-induced cancers.

PMID- 24312187
TI  - Cognitive impairments accompanying rodent mild traumatic brain injury involve p53
      dependent neuronal cell death and are ameliorated by the tetrahydrobenzothiazole
      PFT-alpha.
AB  - With parallels to concussive mild traumatic brain injury (mTBI) occurring in
      humans, anesthetized mice subjected to a single 30 g weight drop mTBI event to
      the right parietal cortex exhibited significant diffuse neuronal degeneration
      that was accompanied by delayed impairments in recognition and spatial memory. To
      elucidate the involvement of reversible p53-dependent apoptosis in this neuronal
      loss and associated cognitive deficits, mice were subjected to experimental mTBI
      followed by the systemic administration of the tetrahydrobenzothiazole p53
      inactivator, PFT-alpha, or vehicle. Neuronal loss was quantified
      immunohistochemically at 72 hr. post-injury by the use of fluoro-Jade B and NeuN
      within the dentate gyrus on both sides of the brain, and recognition and spatial
      memory were assessed by novel object recognition and Y-maze paradigms at 7 and 30
      days post injury. Systemic administration of a single dose of PFT-alpha 1 hr.
      post-injury significantly ameliorated both neuronal cell death and cognitive
      impairments, which were no different from sham control animals. Cellular studies
      on human SH-SY5Y cells and rat primary neurons challenged with glutamate
      excitotoxicity and H2O2 induced oxidative stress, confirmed the ability of PFT
      alpha and a close analog to protect against these TBI associated mechanisms
      mediating neuronal loss. These studies suggest that p53-dependent apoptotic
      mechanisms underpin the neuronal and cognitive losses accompanying mTBI, and that
      these are potentially reversible by p53 inactivation. 

PMID- 24312191
TI  - European Union's public fishing access agreements in developing countries.
AB  - The imperative to increase seafood supply while dealing with its overfished local
      stocks has pushed the European Union (EU) and its Member States to fish in the
      Exclusive Economic Zones of other countries through various types of fishing
      agreements for decades. Although European public fishing agreements are commented
      on regularly and considered to be transparent, this is the first global and
      historical study on the fee regime that governs them. We find that the EU has
      subsidized these agreements at an average of 75% of their cost (financial
      contribution agreed upon in the agreements), while private European business
      interests paid the equivalent of 1.5% of the value of the fish that was
      eventually landed. This raises questions of fisheries benefit-sharing and
      resource-use equity that the EU has the potential to address during the nearly
      completed reform of its Common Fisheries Policy. 

PMID- 24312190
TI  - LncRNA pathway involved in premature preterm rupture of membrane (PPROM): an
      epigenomic approach to study the pathogenesis of reproductive disorders.
AB  - Preterm birth (PTB) is a live birth delivered before 37 weeks of gestation (GW).
      About one-third of PTBs result from the preterm premature rupture of membranes
      (PPROM). Up to the present, the pathogenic mechanisms underlying PPROM are not
      clearly understood. Here, we investigated the differential expression of long
      chain non-coding RNAs (lncRNAs) in placentas of PTBs with PPROM, and their
      possible involvement in the pathogenic pathways leading to PPROM. A total number
      of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas
      of PPROM (group A), which were compared to full-term birth (FTB) (group B), PTB
      (group C), and premature rupture of membrane (PROM) (group D) at full-term,
      respectively. Instead of investigating the individual pathogenic role of each
      lncRNA involved in the molecular mechanism underlying PPROM, we have focused on
      investigating the metabolic pathways and their functions to explore what is the
      likely association and how they are possibly involved in the development of
      PPROM. Six groups, including up-regulation and down-regulation in the comparisons
      of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed
      that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C,
      18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down
      regulated in A vs. B. Functional analysis showed pathways of infection and
      inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton,
      and smooth muscle contraction are the major pathogenic mechanisms involved in the
      development of PPROM. Characterization of these pathways through identification
      of lncRNAs opened new avenues for further investigating the epigenomic mechanisms
      of lncRNAs in PPROM as well as PTB.

PMID- 24312192
TI  - Is "appearing chronically ill" a sign of poor health? A study of diagnostic
      accuracy.
AB  - OBJECTIVE: To determine the sensitivity and specificity of a physician's
      assessment that a patient "appears chronically ill" for the detection of poor
      health status. METHODS: The health status of 126 adult outpatients was determined
      using the 12-Item Short Form Health Survey (SF-12). Physician participants (n =
      111 residents and faculty) viewed photographs of each patient participant and
      assessed whether or not the patient appeared chronically ill. For the entire
      group of physicians, the median sensitivity and specificity of "appearing
      chronically ill" for the detection of poor health status (defined as SF-12
      physical health score below age group norms by at least 1 SD) were calculated.
      The study took place from February 2009 to January 2011. RESULTS: Forty-two
      participants (33%) had an SF-12 physical health score >=1 SD below age group
      norms, and 22 (18%) had a score >=2 SD below age group norms. When poor health
      status was defined as an SF-12 physical score >=1 SD below age group norms, the
      median sensitivity was 38.1% (IQR 28.6-47.6%), specificity 78.6% (IQR 69.0
      84.0%), positive likelihood ratio 1.64 (IQR 1.42-2.15), and negative likelihood
      ratio 0.82 (IQR 0.74-0.87). For an SF-12 physical score >=2 SD below age group
      norms, the median sensitivity was 45.5% (IQR 36.4-54.5%), specificity 76.9% (IQR
      66.3-83.7%), positive likelihood ratio 1.77 (IQR 1.49-2.25), and negative
      likelihood ratio 0.75 (IQR 0.66-0.86). CONCLUSIONS: Our study suggests that a
      physician's assessment that a patient "appears chronically ill" has poor
      sensitivity and modest specificity for the detection of poor health status in
      adult outpatients. The associated likelihood ratios indicate that this assessment
      may have limited diagnostic value.

PMID- 24312193
TI  - The onset of double diffusive convection in a viscoelastic fluid-saturated porous
      layer with non-equilibrium model.
AB  - The onset of double diffusive convection in a viscoelastic fluid-saturated porous
      layer is studied when the fluid and solid phase are not in local thermal
      equilibrium. The modified Darcy model is used for the momentum equation and a two
      field model is used for energy equation each representing the fluid and solid
      phases separately. The effect of thermal non-equilibrium on the onset of double
      diffusive convection is discussed. The critical Rayleigh number and the
      corresponding wave number for the exchange of stability and over-stability are
      obtained, and the onset criterion for stationary and oscillatory convection is
      derived analytically and discussed numerically. 

PMID- 24312194
TI  - Therapeutic DNA vaccination of vertically HIV-infected children: report of the
      first pediatric randomised trial (PEDVAC).
AB  - SUBJECTS: Twenty vertically HIV-infected children, 6-16 years of age, with stable
      viral load control and CD4+ values above 400 cells/mm(3). INTERVENTION: Ten
      subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10
      were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART
      and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C,
      encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took
      place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was
      performed until week 60 and extended to week 96. RESULTS: Safety data showed good
      tolerance of the vaccine. Adherence to ART remained high and persistent during
      the study and did not differ significantly between controls and vaccinees.
      Neither group experienced either virological failure or a decline of CD4+ counts
      from baseline. Higher HIV-specific cellular immune responses were noted
      transiently to Gag but not to other components of the vaccine.
      Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the
      vaccinees than in the controls (p = 0.047), whereas differences in reactivity to
      clade-specific Gag p24, RT or Env did not reach significance. Compared to
      baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in
      the Group B was higher after the vaccination schedule had been completed (p =
      0.031). No increased CD8+ perforin levels were observed in control Group A.
      CONCLUSIONS: The present study demonstrates the feasibility, safety and moderate
      immunogenicity of genetic vaccination in vertically HIV-infected children, paving
      the way for amplified immunotherapeutic approaches in the pediatric population.
      TRIAL REGISTRATION: clinicaltrialsregister.eu _2007-002359-18IT.

PMID- 24312195
TI  - The cannabinoid receptor type 2 as mediator of mesenchymal stromal cell
      immunosuppressive properties.
AB  - Mesenchymal stromal cells are non-hematopoietic, multipotent progenitor cells
      producing cytokines, chemokines, and extracellular matrix proteins that support
      hematopoietic stem cell survival and engraftment, influence immune effector cell
      development, maturation, and function, and inhibit alloreactive T-cell responses.
      The immunosuppressive properties of human mesenchymal stromal cells have
      attracted much attention from immunologists, stem cell biologists and clinicians.
      Recently, the presence of the endocannabinoid system in hematopoietic and neural
      stem cells has been demonstrated. Endocannabinoids, mainly acting through the
      cannabinoid receptor subtype 2, are able to modulate cytokine release and to act
      as immunosuppressant when added to activated T lymphocytes. In the present study,
      we have investigated, through a multidisciplinary approach, the involvement of
      the endocannabinoids in migration, viability and cytokine release of human
      mesenchymal stromal cells. We show, for the first time, that cultures of human
      mesenchymal stromal cells express all of the components of the endocannabinoid
      system, suggesting a potential role for the cannabinoid CB2 receptor as a
      mediator of anti-inflammatory properties of human mesenchymal stromal cells, as
      well as of their survival pathways and their capability to home and migrate
      towards endocannabinoid sources. 

PMID- 24312196
TI  - Suicidal risk factors of recurrent major depression in Han Chinese women.
AB  - The relationship between suicidality and major depression is complex. Socio-
      demography, clinical features, comorbidity, clinical symptoms, and stressful life
      events are important factors influencing suicide in major depression, but these
      are not well defined. Thus, the aim of the present study was to assess the
      associations between the above-mentioned factors and suicide ideation, suicide
      plan, and suicide attempt in 6008 Han Chinese women with recurrent major
      depression (MD). Patients with any suicidality had significantly more MD
      symptoms, a significantly greater number of stressful life events, a positive
      family history of MD, a greater number of episodes, a significant experience of
      melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized
      anxiety disorder (GAD), social phobia, and animal phobia was seen in suicidal
      patients. The present findings indicate that specific factors act to increase the
      likelihood of suicide in MD. Our results may help improve the clinical assessment
      of suicide risk in depressed patients, especially for women. 

PMID- 24312198
TI  - Assessing differential expression in two-color microarrays: a resampling-based
      empirical Bayes approach.
AB  - Microarrays are widely used for examining differential gene expression,
      identifying single nucleotide polymorphisms, and detecting methylation loci.
      Multiple testing methods in microarray data analysis aim at controlling both Type
      I and Type II error rates; however, real microarray data do not always fit their
      distribution assumptions. Smyth's ubiquitous parametric method, for example,
      inadequately accommodates violations of normality assumptions, resulting in
      inflated Type I error rates. The Significance Analysis of Microarrays, another
      widely used microarray data analysis method, is based on a permutation test and
      is robust to non-normally distributed data; however, the Significance Analysis of
      Microarrays method fold change criteria are problematic, and can critically alter
      the conclusion of a study, as a result of compositional changes of the control
      data set in the analysis. We propose a novel approach, combining resampling with
      empirical Bayes methods: the Resampling-based empirical Bayes Methods. This
      approach not only reduces false discovery rates for non-normally distributed
      microarray data, but it is also impervious to fold change threshold since no
      control data set selection is needed. Through simulation studies, sensitivities,
      specificities, total rejections, and false discovery rates are compared across
      the Smyth's parametric method, the Significance Analysis of Microarrays, and the
      Resampling-based empirical Bayes Methods. Differences in false discovery rates
      controls between each approach are illustrated through a preterm delivery
      methylation study. The results show that the Resampling-based empirical Bayes
      Methods offer significantly higher specificity and lower false discovery rates
      compared to Smyth's parametric method when data are not normally distributed. The
      Resampling-based empirical Bayes Methods also offers higher statistical power
      than the Significance Analysis of Microarrays method when the proportion of
      significantly differentially expressed genes is large for both normally and non
      normally distributed data. Finally, the Resampling-based empirical Bayes Methods
      are generalizable to next generation sequencing RNA-seq data analysis. 

PMID- 24312197
TI  - Sensitivity of Aspergillus nidulans to the cellulose synthase inhibitor
      dichlobenil: insights from wall-related genes' expression and ultrastructural
      hyphal morphologies.
AB  - The fungal cell wall constitutes an important target for the development of
      antifungal drugs, because of its central role in morphogenesis, development and
      determination of fungal-specific molecular features. Fungal walls are
      characterized by a network of interconnected glycoproteins and polysaccharides,
      namely alpha-, beta-glucans and chitin. Cell walls promptly and dynamically
      respond to environmental stimuli by a signaling mechanism, which triggers, among
      other responses, modulations in wall biosynthetic genes' expression. Despite the
      absence of cellulose in the wall of the model filamentous fungus Aspergillus
      nidulans, we found in this study that fungal growth, spore germination and
      morphology are affected by the addition of the cellulose synthase inhibitor
      dichlobenil. Expression analysis of selected genes putatively involved in cell
      wall biosynthesis, carried out at different time points of drug exposure (i.e. 0,
      1, 3, 6 and 24 h), revealed increased expression for the putative mixed linkage
      beta-1,3;1,4 glucan synthase celA together with the beta-1,3-glucan synthase fksA
      and the Rho-related GTPase rhoA. We also compared these data with the response to
      Congo Red, a known plant/fungal drug affecting both chitin and cellulose
      biosynthesis. The two drugs exerted different effects at the cell wall level, as
      shown by gene expression analysis and the ultrastructural features observed
      through atomic force microscopy and scanning electron microscopy. Although the
      concentration of dichlobenil required to affect growth of A. nidulans is
      approximately 10-fold higher than that required to inhibit plant cellulose
      biosynthesis, our work for the first time demonstrates that a cellulose
      biosynthesis inhibitor affects fungal growth, changes fungal morphology and
      expression of genes connected to fungal cell wall biosynthesis. 

PMID- 24312199
TI  - Exercise training in transgenic mice is associated with attenuation of early
      breast cancer growth in a dose-dependent manner.
AB  - Epidemiological research suggests that regular physical activity confers
      beneficial effects that mediate an anti-tumor response and may reduce cancer
      recurrence. It is unclear what amount of physical activity is necessary to exert
      such a protective effect and what mechanisms are involved. We investigated the
      effects of voluntary wheel running on tumor progression and cytokine gene
      expression in the transgenic polyoma middle T oncoprotein (PyMT) mouse model of
      invasive breast cancer. Runners showed significantly reduced tumor sizes compared
      with non-runners after 3 weeks of running (p <= 0.01), and the greater the
      running distance the smaller the tumor size (Pearson's r = -0.61, p <= 0.04, R(2)
      = 0.38). Mice running greater than 150 km per week had a significantly attenuated
      tumor size compared with non-runners (p <= 0.05). Adipose tissue mass was
      inversely correlated with tumor size in runners (Pearson's r = -0.77, p = 0.014)
      but not non-runners. Gene expression of CCL22, a cytokine associated with
      recruitment of immunosuppressive T regulatory cells, was decreased in tumors of
      runners compared to non-runners (p <= 0.005). No differences in tumor burden or
      metastatic burden were observed between runners and non-runners after ten weeks
      of running when the study was completed. We conclude that voluntary wheel running
      in PyMT mice correlates with an attenuation in tumor progression early during the
      course of invasive breast cancer. This effect is absent in the later stages of
      overwhelming tumor burden even though cytokine signaling for immunosuppressive
      regulatory T cells was down regulated. These observations suggest that the
      initiation of moderate exercise training for adjunctive therapeutic benefit early
      in the course of invasive breast cancer should be considered for further
      investigation.

PMID- 24312200
TI  - Fishing long-fingered bats (Myotis capaccinii) prey regularly upon exotic fish.
AB  - The long-fingered bat Myotis capaccinii is a European trawling bat reported to
      feed on fish in several Mediterranean locations, but the ecological circumstances
      of this behavior have not yet been studied. To elucidate the importance of
      fishing in this bat's diet, we evaluated the frequency and seasonal variation of
      fish remains in 3,000 fecal pellets collected from M. capaccinii at a nursery
      roost in Denia (Eastern Iberian Peninsula) in 2008, 2009, and 2010. Fish
      consumption occurred evenly throughout the year. All otoliths found in feces were
      identified as belonging to the surface-feeding fish Gambusia holbrooki. Measuring
      otoliths, we estimated that the mean size of consumed fish was significantly
      smaller than the mean measured for available fish, suggesting that the long
      fingered bat's relatively small body may constrain its handling of larger prey.
      Of note, one bat had eaten 15 fish, showing that fish may be a locally or
      seasonally important trophic resource for this species. By capturing 15 bats and
      radio-tracking the four with the most fish remains in their droppings, we also
      identified fishing areas, including a single fishing ground comprising several
      ponds within a golf course. Ponds hold a high density of G. holbrooki, suggesting
      that the amount of fish at the water surface may be the principal factor
      triggering fishing. The observed six-fold increase in percentage of consumed fish
      across the study period may be related to recent pond-building in the area. We
      discuss whether this quick behavioral response is a novel feature of M.
      capaccinii or an intrinsic feature that has erupted and faded locally along the
      species' history. 

PMID- 24312201
TI  - Attenuated expression of apoptosis stimulating protein of p53-2 (ASPP2) in human
      acute leukemia is associated with therapy failure.
AB  - Inactivation of the p53 pathway is a universal event in human cancers and
      promotes tumorigenesis and resistance to chemotherapy. Inactivating p53 mutations
      are uncommon in non-complex karyotype leukemias, thus the p53-pathway must be
      inactivated by other mechanisms. The Apoptosis Stimulating Protein of p53-2
      (ASPP2) is a damage-inducible p53-binding protein that enhances apoptosis at
      least in part through a p53-mediated pathway. We have previously shown, that
      ASPP2 is an independent haploinsufficient tumor suppressor in vivo. Now, we
      reveal that ASPP2 expression is significantly attenuated in acute myeloid and
      lymphoid leukemia - especially in patients with an unfavorable prognostic risk
      profile and patients who fail induction chemotherapy. In line, knock down of
      ASPP2 in expressing leukemia cell lines and native leukemic blasts attenuates
      damage-induced apoptosis. Furthermore, cultured blasts derived from high-risk
      leukemias fail to induce ASPP2 expression upon anthracycline treatment. The
      mechanisms of ASPP2 dysregulation are unknown. We provide evidence that
      attenuation of ASPP2 is caused by hypermethylation of the promoter and 5'UTR
      regions in native leukemia blasts. Together, our results suggest that ASPP2
      contributes to the biology of leukemia and expression should be further explored
      as a potential prognostic and/or predictive biomarker to monitor therapy
      responses in acute leukemia. 

PMID- 24312202
TI  - Molecular modeling reveals the novel inhibition mechanism and binding mode of
      three natural compounds to staphylococcal alpha-hemolysin.
AB  - alpha-Hemolysin (alpha-HL) is a self-assembling, channel-forming toxin that is
      produced as a soluble monomer by Staphylococcus aureus strains. Until now, alpha
      HL has been a significant virulence target for the treatment of S. aureus
      infection. In our previous report, we demonstrated that some natural compounds
      could bind to alpha-HL. Due to the binding of those compounds, the conformational
      transition of alpha-HL from the monomer to the oligomer was blocked, which
      resulted in inhibition of the hemolytic activity of alpha-HL. However, these
      results have not indicated how the binding of the alpha-HL inhibitors influence
      the conformational transition of the whole protein during the oligomerization
      process. In this study, we found that three natural compounds, Oroxylin A 7-O
      glucuronide (OLG), Oroxin A (ORA), and Oroxin B (ORB), when inhibiting the
      hemolytic activity of alpha-HL, could bind to the "stem" region of alpha-HL. This
      was completed using conventional Molecular Dynamics (MD) simulations. By
      interacting with the novel binding sites of alpha-HL, the ligands could form
      strong interactions with both sides of the binding cavity. The results of the
      principal component analysis (PCA) indicated that because of the inhibitors that
      bind to the "stem" region of alpha-HL, the conformational transition of alpha-HL
      from the monomer to the oligomer was restricted. This caused the inhibition of
      the hemolytic activity of alpha-HL. This novel inhibition mechanism has been
      confirmed by both the steered MD simulations and the experimental data obtained
      from a deoxycholate-induced oligomerization assay. This study can facilitate the
      design of new antibacterial drugs against S. aureus. 

PMID- 24312203
TI  - Contribution of the microbial communities detected on an oil painting on canvas
      to its biodeterioration.
AB  - In this study, we investigated the microbial community (bacteria and fungi)
      colonising an oil painting on canvas, which showed visible signs of
      biodeterioration. A combined strategy, comprising culture-dependent and 
      independent techniques, was selected. The results derived from the two techniques
      were disparate. Most of the isolated bacterial strains belonged to related
      species of the phylum Firmicutes, as Bacillus sp. and Paenisporosarcina sp.,
      whereas the majority of the non-cultivable members of the bacterial community
      were shown to be related to species of the phylum Proteobacteria, as
      Stenotrophomonas sp. Fungal communities also showed discrepancies: the isolated
      fungal strains belonged to different genera of the order Eurotiales, as
      Penicillium and Eurotium, and the non-cultivable belonged to species of the order
      Pleosporales and Saccharomycetales. The cultivable microorganisms, which
      exhibited enzymatic activities related to the deterioration processes, were
      selected to evaluate their biodeteriorative potential on canvas paintings; namely
      Arthrobacter sp. as the representative bacterium and Penicillium sp. as the
      representative fungus. With this aim, a sample taken from the painting studied in
      this work was examined to determine the stratigraphic sequence of its cross
      section. From this information, "mock paintings," simulating the structure of the
      original painting, were prepared, inoculated with the selected bacterial and
      fungal strains, and subsequently examined by micro-Fourier Transform Infrared
      spectroscopy, in order to determine their potential susceptibility to microbial
      degradation. The FTIR-spectra revealed that neither Arthrobacter sp. nor
      Penicillium sp. alone, were able to induce chemical changes on the various
      materials used to prepare "mock paintings." Only when inoculated together, could
      a synergistic effect on the FTIR-spectra be observed, in the form of a variation
      in band position on the spectrum. 

PMID- 24312205
TI  - Personality variation in little brown bats.
AB  - Animal personality or temperament refers to individual differences in behaviour
      that are repeatable over time and across contexts. Personality has been linked to
      life-history traits, energetic traits and fitness, with implications for the
      evolution of behaviour. Personality has been quantified for a range of taxa
      (e.g., fish, songbirds, small mammals) but, so far, there has been little work on
      personality in bats, despite their diversity and potential as a model taxon for
      comparative studies. We used a novel environment test to quantify personality in
      little brown bats (Myotis lucifugus) and assess the short-term repeatability of a
      range of behaviours. We tested the hypothesis that development influences values
      of personality traits and predicted that trait values associated with activity
      would increase between newly volant, pre-weaning young-of-the-year (YOY) and more
      mature, self-sufficient YOY. We identified personality dimensions that were
      consistent with past studies of other taxa and found that these traits were
      repeatable over a 24-hour period. Consistent with our prediction, older YOY
      captured at a fall swarming site prior to hibernation had higher activity scores
      than younger YOY bats captured at a maternity colony, suggesting that personality
      traits vary as development progresses in YOY bats. Thus, we found evidence of
      short-term consistency of personality within individuals but with the potential
      for temporal flexibility of traits, depending on age. 

PMID- 24312204
TI  - Polymorphisms of genes in neurotransmitter systems were associated with alcohol
      use disorders in a Tibetan population.
AB  - Studies of linkage and association in various ethnic populations have revealed
      many predisposing genes of multiple neurotransmitter systems for alcohol use
      disorders (AUD). However, evidence often is contradictory regarding the
      contribution of most candidate genes to the susceptibility of AUD. We, therefore,
      performed a case-control study to investigate the possible associations of genes
      selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan
      community population in China. AUD cases (N = 281) with an alcohol use disorder
      identification test (AUDIT) score >=10, as well as healthy controls (N = 277)
      with an AUDIT score <=5, were recruited. All participants were genotyped for 366
      single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved
      in neurotransmitter systems. Association analyses were performed using PLINK
      version 1.07 software. Allelic analyses before adjustment for multiple tests
      showed that 15 polymorphisms within seven genes were associated with AUD
      (p<0.05). After adjustment for the number of SNPs genotyped within each gene,
      only the association of a single marker (rs10044881) in HTR4 remained
      statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298
      and rs10044881) showed that the haplotype AG was significantly associated with
      the protective effect for AUD. In conclusion, the present study discovered that
      the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition,
      this Tibetan population sample marginally replicated previous evidence regarding
      the associations of six genes in AUD.

PMID- 24312206
TI  - A new methodology for studying dynamics of aerosol particles in sneeze and cough
      using a digital high-vision, high-speed video system and vector analyses.
AB  - Microbial pathogens of respiratory infectious diseases are often transmitted
      through particles in sneeze and cough. Therefore, understanding the particle
      movement is important for infection control. Images of a sneeze induced by nasal
      cavity stimulation by healthy adult volunteers, were taken by a digital high
      vision, high-speed video system equipped with a computer system and treated as a
      research model. The obtained images were enhanced electronically, converted to
      digital images every 1/300 s, and subjected to vector analysis of the
      bioparticles contained in the whole sneeze cloud using automatic image processing
      software. The initial velocity of the particles or their clusters in the sneeze
      was greater than 6 m/s, but decreased as the particles moved forward; the
      momentums of the particles seemed to be lost by 0.15-0.20 s and started a
      diffusion movement. An approximate equation of a function of elapsed time for
      their velocity was obtained from the vector analysis to represent the dynamics of
      the front-line particles. This methodology was also applied for a cough.
      Microclouds contained in a smoke exhaled with a voluntary cough by a volunteer
      after smoking one breath of cigarette, were traced as the visible, aerodynamic
      surrogates for invisible bioparticles of cough. The smoke cough microclouds had
      an initial velocity greater than 5 m/s. The fastest microclouds were located at
      the forefront of cloud mass that moving forward; however, their velocity clearly
      decreased after 0.05 s and they began to diffuse in the environmental airflow.
      The maximum direct reaches of the particles and microclouds driven by sneezing
      and coughing unaffected by environmental airflows were estimated by calculations
      using the obtained equations to be about 84 cm and 30 cm from the mouth,
      respectively, both achieved in about 0.2 s, suggesting that data relating to the
      dynamics of sneeze and cough became available by calculation. 

PMID- 24312207
TI  - Quantifying reproducibility in computational biology: the case of the
      tuberculosis drugome.
AB  - How easy is it to reproduce the results found in a typical computational biology
      paper? Either through experience or intuition the reader will already know that
      the answer is with difficulty or not at all. In this paper we attempt to quantify
      this difficulty by reproducing a previously published paper for different classes
      of users (ranging from users with little expertise to domain experts) and suggest
      ways in which the situation might be improved. Quantification is achieved by
      estimating the time required to reproduce each of the steps in the method
      described in the original paper and make them part of an explicit workflow that
      reproduces the original results. Reproducing the method took several months of
      effort, and required using new versions and new software that posed challenges to
      reconstructing and validating the results. The quantification leads to
      "reproducibility maps" that reveal that novice researchers would only be able to
      reproduce a few of the steps in the method, and that only expert researchers with
      advance knowledge of the domain would be able to reproduce the method in its
      entirety. The workflow itself is published as an online resource together with
      supporting software and data. The paper concludes with a brief discussion of the
      complexities of requiring reproducibility in terms of cost versus benefit, and a
      desiderata with our observations and guidelines for improving reproducibility.
      This has implications not only in reproducing the work of others from published
      papers, but reproducing work from one's own laboratory. 

PMID- 24312208
TI  - Genome-wide and paternal diversity reveal a recent origin of human populations in
      North Africa.
AB  - The geostrategic location of North Africa as a crossroad between three continents
      and as a stepping-stone outside Africa has evoked anthropological and genetic
      interest in this region. Numerous studies have described the genetic landscape of
      the human population in North Africa employing paternal, maternal, and biparental
      molecular markers. However, information from these markers which have different
      inheritance patterns has been mostly assessed independently, resulting in an
      incomplete description of the region. In this study, we analyze uniparental and
      genome-wide markers examining similarities or contrasts in the results and
      consequently provide a comprehensive description of the evolutionary history of
      North Africa populations. Our results show that both males and females in North
      Africa underwent a similar admixture history with slight differences in the
      proportions of admixture components. Consequently, genome-wide diversity show
      similar patterns with admixture tests suggesting North Africans are a mixture of
      ancestral populations related to current Africans and Eurasians with more
      affinity towards the out-of-Africa populations than to sub-Saharan Africans. We
      estimate from the paternal lineages that most North Africans emerged ~15,000
      years ago during the last glacial warming and that population splits started
      after the desiccation of the Sahara. Although most North Africans share a common
      admixture history, the Tunisian Berbers show long periods of genetic isolation
      and appear to have diverged from surrounding populations without subsequent
      mixture. On the other hand, continuous gene flow from the Middle East made
      Egyptians genetically closer to Eurasians than to other North Africans. We show
      that genetic diversity of today's North Africans mostly captures patterns from
      migrations post Last Glacial Maximum and therefore may be insufficient to inform
      on the initial population of the region during the Middle Paleolithic period.

PMID- 24312209
TI  - High morbidity during treatment and residual pulmonary disability in pulmonary
      tuberculosis: under-recognised phenomena.
AB  - BACKGROUND: In pulmonary tuberculosis (PTB), morbidity during treatment and
      residual pulmonary disability can be under-estimated. METHODS: Among adults with
      smear-positive PTB at an outpatient clinic in Papua, Indonesia, we assessed
      morbidity at baseline and during treatment, and 6-month residual disability, by
      measuring functional capacity (six-minute walk test [6MWT] and pulmonary
      function), quality of life (St George's Respiratory Questionnaire [SGRQ]) and
      Adverse Events ([AE]: new symptoms not present at outset). Results were compared
      with findings in locally-recruited volunteers. RESULTS: 200 PTB patients and 40
      volunteers were enrolled. 6WMT was 497m (interquartile range 460-529) in controls
      versus 408m (IQR 346-450) in PTB patients at baseline (p<0.0001) and 470m (IQR
      418-515) in PTB patients after 6 months (p=0.02 versus controls). SGRQ total
      score was 0 units (IQR 0-2.9) in controls, versus 36.9 (27.4-52.8) in PTB
      patients at baseline (p<0.0001) and 4.3 (1.7-8.8) by 6 months (p<0.0001). Mean
      percentage of predicted FEV1 was 92% (standard deviation 19.9) in controls,
      versus 63% (19.4) in PTB patients at baseline (p<0.0001) and 71% (17.5) by 6
      months (p<0.0001). After 6 months, 27% of TB patients still had at least moderate
      severe pulmonary function impairment, and 57% still had respiratory symptoms,
      despite most achieving 'successful' treatment outcomes, and reporting good
      quality of life. More-advanced disease at baseline (longer illness duration,
      worse baseline X-ray) and HIV positivity predicted residual disability. AE at any
      time during treatment were common: itch 59%, arthralgia 58%, headache 40%, nausea
      33%, vomiting 16%. CONCLUSION: We found high 6-month residual pulmonary
      disability and high AE rates. Although PTB treatment is highly successful, the
      extent of morbidity during treatment and residual impairment could be overlooked
      if not specifically sought. Calculations of PTB-related burden of disease should
      acknowledge that TB-related morbidity does not stop at 6 months. Early case
      detection and treatment are key in minimising residual impairment.

PMID- 24312210
TI  - Till death do us part: stable sponge-bacteria associations under thermal and food
      shortage stresses.
AB  - Sporadic mass mortality events of Mediterranean sponges following periods of
      anomalously high temperatures or longer than usual stratification of the seawater
      column (i.e. low food availability) suggest that these animals are sensitive to
      environmental stresses. The Mediterranean sponges Ircinia fasciculata and I. oros
      harbor distinct, species-specific bacterial communities that are highly stable
      over time and space but little is known about how anomalous environmental
      conditions affect the structure of the resident bacterial communities. Here, we
      monitored the bacterial communities in I. fasciculata (largely affected by mass
      mortalities) and I. oros (overall unaffected) maintained in aquaria during 3
      weeks under 4 treatments that mimicked realistic stress pressures: control
      conditions (13 degrees C, unfiltered seawater), low food availability (13 degrees
      C, 0.1 um-filtered seawater), elevated temperatures (25 degrees C, unfiltered
      seawater), and a combination of the 2 stressors (25 degrees C, 0.1 um-filtered
      seawater). Bacterial community structure was assessed using terminal restriction
      fragment length polymorphism (T-RFLP) analysis of 16S rRNA gene sequences and
      transmission electron microscopy (TEM). As I. fasciculata harbors cyanobacteria,
      we also measured chlorophyll a (chl a) levels in this species. Multivariate
      analysis revealed no significant differences in bacterial T-RFLP profiles among
      treatments for either host sponge species, indicating no effect of high
      temperatures and food shortage on symbiont community structure. In I.
      fasciculata, chl a content did not significantly differ among treatments although
      TEM micrographs revealed some cyanobacteria cells undergoing degradation when
      exposed to both elevated temperature and food shortage conditions. Arguably,
      longer-term treatments (months) could have eventually affected bacterial
      community structure. However, we evidenced no appreciable decay of the symbiotic
      community in response to medium-term (3 weeks) environmental anomalies purported
      to cause the recurrent sponge mortality episodes. Thus, changes in symbiont
      structure are not likely the proximate cause for these reported mortality events.

PMID- 24312211
TI  - Information transmission in a neuron-astrocyte coupled model.
AB  - A coupled model containing two neurons and one astrocyte is constructed by
      integrating Hodgkin-Huxley neuronal model and Li-Rinzel calcium model. Based on
      this hybrid model, information transmission between neurons is studied
      numerically. Our results show that when the successive spikes are produced in
      neuron 1 (N1), the bursting-like spikes (BLSs) occur in two neurons
      simultaneously during the spikes being transferred to neuron 2 (N2). The
      existence of the astrocyte and a higher expression level of mGluRs facilitate the
      occurrence of BLSs, but the rate of occurrence is not sensitive to the
      parameters. Furthermore, time delay tau occurs during the information
      transmission, and tau is almost independent of the effect of the astrocyte.
      Additionally, we found that low coupling strength may result in the distortion of
      the information, and this distortion is also proven to be almost independent of
      the astrocyte. 

PMID- 24312212
TI  - "Terror birds" (Phorusrhacidae) from the Eocene of Europe imply trans-Tethys
      dispersal.
AB  - BACKGROUND: Phorusrhacidae was a clade including middle-sized to giant
      terrestrial carnivorous birds, known mainly from the Cenozoic of South America,
      but also occurring in the Plio-Pleistocene of North America and the Eocene of
      Africa. Previous reports of small phorusrhacids in the Paleogene of Europe have
      been dismissed as based on non-phorusrhacid material. METHODOLOGY: we have re
      examined specimens of large terrestrial birds from the Eocene (late Lutetian) of
      France and Switzerland previously referred to gastornithids and ratites and have
      identified them as belonging to a phorusrhacid for which the name Eleutherornis
      cotei should be used. CONCLUSIONS/SIGNIFICANCE: The occurrence of a phorusrhacid
      in the late Lutetian of Europe indicates that these flightless birds had a wider
      geographical distribution than previously recognized. The likeliest
      interpretation is that they dispersed from Africa, where the group is known in
      the Eocene, which implies crossing the Tethys Sea. The Early Tertiary
      distribution of phorusrhacids can be best explained by transoceanic dispersal,
      across both the South Atlantic and the Tethys.

PMID- 24312213
TI  - Involvement of and interaction between WNT10A and EDA mutations in tooth agenesis
      cases in the Chinese population.
AB  - BACKGROUND: Dental agenesis is the most common, often heritable, developmental
      anomaly in humans. Although WNT10A gene mutations are known to cause rare
      syndromes associated with tooth agenesis, including onycho-odontodermal dysplasia
      (OODD), Schopf-Schulz-Passarge syndrome (SSPS), hypohidrotic ectodermal dysplasia
      (HED), and more than half of the cases of isolated oligodontia recently, the
      genotype-phenotype correlations and the mode of inheritance of WNT10A mutations
      remain unclear. The phenotypic expression with WNT10A mutations shows a high
      degree of variability, suggesting that other genes might function with WNT10A in
      regulating ectodermal organ development. Moreover, the involvement of mutations
      in other genes, such as EDA, which is also associated with HED and isolated tooth
      agenesis, is not clear. Therefore, we hypothesized that EDA mutations interact
      with WNT10A mutations to play a role in tooth agenesis. Additionally, EDA, EDAR,
      and EDARADD encode signaling molecules in the Eda/Edar/NF-kappaB signaling
      pathways, we also checked EDAR and EDARADD in this study. METHODS: WNT10A, EDA,
      EDAR and EDARADD were sequenced in 88 patients with isolated oligodontia and 26
      patients with syndromic tooth agenesis. The structure of two mutated WNT10A and
      two mutated EDA proteins was analyzed. RESULTS: Digenic mutations of both WNT10A
      and EDA were identified in 2 of 88 (2.27%) isolated oligodontia cases and 4 of 26
      (15.38%) syndromic tooth agenesis cases. No mutation in EDAR or EDARADD gene was
      found. CONCLUSIONS: WNT10A and EDA digenic mutations could result in oligodontia
      and syndromic tooth agenesis in the Chinese population. Moreover, our results
      will greatly expand the genotypic spectrum of tooth agenesis.

PMID- 24312214
TI  - Social origins of rhythm? Synchrony and temporal regularity in human
      vocalization.
AB  - Humans have a capacity to perceive and synchronize with rhythms. This is unusual
      in that only a minority of other species exhibit similar behavior. Study of
      synchronizing species (particularly anurans and insects) suggests that
      simultaneous signal production by different individuals may play a critical role
      in the development of regular temporal signaling. Accordingly, we investigated
      the link between simultaneous signal production and temporal regularity in our
      own species. Specifically, we asked whether inter-individual synchronization of a
      behavior that is typically irregular in time, speech, could lead to evenly-paced
      or "isochronous" temporal patterns. Participants read nonsense phrases aloud with
      and without partners, and we found that synchronous reading resulted in greater
      regularity of durational intervals between words. Comparison of same-gender
      pairings showed that males and females were able to synchronize their temporal
      speech patterns with equal skill. These results demonstrate that the shared goal
      of synchronization can lead to the development of temporal regularity in
      vocalizations, suggesting that the origins of musical rhythm may lie in
      cooperative social interaction rather than in sexual selection. 

PMID- 24312215
TI  - Thermal stress induced aggregation of aquaporin 0 (AQP0) and protection by alpha
      crystallin via its chaperone function.
AB  - Aquaporin 0 (AQP0) formerly known as membrane intrinsic protein (MIP), is
      expressed exclusively in the lens during terminal differentiation of fiber cells.
      AQP0 plays an important role not only in the regulation of water content but also
      in cell-to-cell adhesion of the lens fiber cells. We have investigated the
      thermal stress-induced structural alterations of detergent (octyl glucoside)
      solubilized calf lens AQP0. The results show an increase in the amount of AQP0
      that aggregated as the temperature increased from 40 degrees C to 65 degrees C.
      alpha-Crystallin, molecular chaperone abundantly present in the eye lens,
      completely prevented the AQP0 aggregation at a 1?1 (weight/weight) ratio. Since
      alpha-crystallin consists of two gene products namely alphaA- and alphaB
      crystallins, we have tested the recombinant proteins on their ability to prevent
      thermal-stress induced AQP0 aggregation. In contrast to the general observation
      made with other target proteins, alphaA-crystallin exhibited better chaperone
      like activity towards AQP0 compared to alphaB-crystallin. Neither post
      translational modifications (glycation) nor C-terminus truncation of AQP0 have
      any appreciable effect on its thermal aggregation properties. alpha-Crystallin
      offers similar protection against thermal aggregation as in the case of the
      unmodified AQP0, suggesting that alphacrystallin may bind to either intracellular
      loops or other residues of AQP0 that become exposed during thermal stress. Far-UV
      circular dichroism studies indicated a loss of alphahelical structures when AQP0
      was subjected to temperatures above 45 degrees C, and the presence of alpha
      crystallin stabilized these secondary structures. We report here, for the first
      time, that alpha-crystallin protects AQP0 from thermal aggregation. Since stress
      induced structural perturbations of AQP0 may affect the integrity of the lens,
      presence of the molecular chaperone, alpha-crystallin (particularly alphaA
      crystallin) in close proximity to the lens membrane is physiologically relevant. 

PMID- 24312216
TI  - Antioxidant, antibacterial and antischistosomal activities of extracts from
      Grateloupia livida (Harv). Yamada.
AB  - The present study was designated to evaluate the antioxidant, antibacterial and
      antischistosomal activities of Grateloupia livida (GL) extracts in vitro. A GL
      Ethanol extract (EE) was separated into petroleum ether (PE), ethyl acetate (EA),
      n-butyl alcohol (BuOH) and aqueous (AQ) fractions to fractionate the polar and
      non-polar compounds in the EE. Extracts antioxidant activities were evaluated in
      vitro by DPPH radical-scavenging, deoxyribose radical scavenging, and beta
      carotene bleaching assays, all using butylated hydroxytoluene (BHT) as the
      reference antioxidant compound. The most effective antioxidant properties were
      observed in the PE fraction in all three assays. Antimicrobial testing showed
      that the PE fraction exhibited broad-spectrum antimicrobial activity, with the PE
      fraction also exhibiting strong activity against the human pathogenic trematode
      S. japonicum adult worm. In order to investigate the relationships between
      bioactivity and chemical composition, the chemical composition of the PE fraction
      was analyzed by gas chromatography-mass spectrometry (GC-MS). In total, 25
      components were identified in the PE fraction, most of which have known
      antioxidant and antimicrobial activities. However, none of the compounds have
      reported activity against Schistosoma, suggesting that the schistosomicidal
      activity of the PE fraction may be related to minor constituents present in the
      extract, or governed by more intricate synergistic or additive relationships.
      Finally, fractions with the greatest biological activity displayed neither
      cellular cytotoxicity, at concentrations up to 100 ug/ml, or acute oral toxicity
      in mice, at doses up to 2000 mg/kg. Based on antioxidant, antimicrobial,
      antischistosomal activities, and low toxicity, the PE fraction possesses
      properties useful for food preservation and overall improvement of human health. 

PMID- 24312217
TI  - A novel pulse-chase SILAC strategy measures changes in protein decay and
      synthesis rates induced by perturbation of proteostasis with an Hsp90 inhibitor.
AB  - Standard proteomics methods allow the relative quantitation of levels of
      thousands of proteins in two or more samples. While such methods are invaluable
      for defining the variations in protein concentrations which follow the
      perturbation of a biological system, they do not offer information on the
      mechanisms underlying such changes. Expanding on previous work [1], we developed
      a pulse-chase (pc) variant of SILAC (stable isotope labeling by amino acids in
      cell culture). pcSILAC can quantitate in one experiment and for two conditions
      the relative levels of proteins newly synthesized in a given time as well as the
      relative levels of remaining preexisting proteins. We validated the method
      studying the drug-mediated inhibition of the Hsp90 molecular chaperone, which is
      known to lead to increased synthesis of stress response proteins as well as the
      increased decay of Hsp90 "clients". We showed that pcSILAC can give information
      on changes in global cellular proteostasis induced by treatment with the
      inhibitor, which are normally not captured by standard relative quantitation
      techniques. Furthermore, we have developed a mathematical model and computational
      framework that uses pcSILAC data to determine degradation constants kd and
      synthesis rates Vs for proteins in both control and drug-treated cells. The
      results show that Hsp90 inhibition induced a generalized slowdown of protein
      synthesis and an increase in protein decay. Treatment with the inhibitor also
      resulted in widespread protein-specific changes in relative synthesis rates,
      together with variations in protein decay rates. The latter were more restricted
      to individual proteins or protein families than the variations in synthesis. Our
      results establish pcSILAC as a viable workflow for the mechanistic dissection of
      changes in the proteome which follow perturbations. Data are available via
      ProteomeXchange with identifier PXD000538. 

PMID- 24312218
TI  - Evaluation of the potential effect of transgenic rice expressing Cry1Ab on the
      hematology and enzyme activity in organs of female Swiss rats.
AB  - To assess the safety of transgenic rice expressing Cry1Ab protein to vertebrates,
      the effect of Cry1Ab rice on broad health indicators in blood and various organs
      of Swiss rats were analyzed. The 30 and 90 day safety studies of Cry1Ab rice on
      female Swiss rats revealed that Cry1Ab rice had no significant effect on the
      several elements of blood lymph including hemogram, calcium ion concentration and
      apoptosis rate of lymphocytes, indicating that Cry1Ab protein could not affect
      the blood lymph of Swiss rat. Similarly, Cry1Ab rice had no effect on enzyme
      activities in a variety of organs of Swiss rat. However, Cry1Ab rice did have
      significant effects on the blood biochemistry indexes including urea,
      triglyceride (TG), glutamic oxalacetic transaminase (AST) and alkaline
      phosphatase (ALP) after the rats were fed with Cry1Ab rice for 30 days, but not
      after 90 days, indicating that Cry1Ab protein may influence blood metabolism for
      a short duration. Quantitative real-time PCR (qPCR) analysis of the 6 genes
      encoding enzymes responsible for the major detoxification functions of liver
      revealed that Cry1Ab rice exerted no influences on the levels of these
      transcripts in liver of Swiss rat, indicating that significant differences
      registered in part of the blood biochemical parameters in the 30 day study might
      result from other untested organs or tissues in response to the stress of
      exogenous Cry1Ab protein. The results suggest that Cry1Ab protein has no
      significant long-term (90 day) effects on female Swiss rat. 

PMID- 24312219
TI  - Dynamic impacts of the inhibition of the molecular chaperone Hsp90 on the T-cell
      proteome have implications for anti-cancer therapy.
AB  - The molecular chaperone Hsp90-dependent proteome represents a complex protein
      network of critical biological and medical relevance. Known to associate with
      proteins with a broad variety of functions termed clients, Hsp90 maintains key
      essential and oncogenic signalling pathways. Consequently, Hsp90 inhibitors are
      being tested as anti-cancer drugs. Using an integrated systematic approach to
      analyse the effects of Hsp90 inhibition in T-cells, we quantified differential
      changes in the Hsp90-dependent proteome, Hsp90 interactome, and a selection of
      the transcriptome. Kinetic behaviours in the Hsp90-dependent proteome were
      assessed using a novel pulse-chase strategy (Fierro-Monti et al., accompanying
      article), detecting effects on both protein stability and synthesis. Global and
      specific dynamic impacts, including proteostatic responses, are due to direct
      inhibition of Hsp90 as well as indirect effects. As a result, a decrease was
      detected in most proteins that changed their levels, including known Hsp90
      clients. Most likely, consequences of the role of Hsp90 in gene expression
      determined a global reduction in net de novo protein synthesis. This decrease
      appeared to be greater in magnitude than a concomitantly observed global increase
      in protein decay rates. Several novel putative Hsp90 clients were validated, and
      interestingly, protein families with critical functions, particularly the Hsp90
      family and cofactors themselves as well as protein kinases, displayed strongly
      increased decay rates due to Hsp90 inhibitor treatment. Remarkably, an upsurge in
      survival pathways, involving molecular chaperones and several oncoproteins, and
      decreased levels of some tumour suppressors, have implications for anti-cancer
      therapy with Hsp90 inhibitors. The diversity of global effects may represent a
      paradigm of mechanisms that are operating to shield cells from proteotoxic
      stress, by promoting pro-survival and anti-proliferative functions. Data are
      available via ProteomeXchange with identifier PXD000537. 

PMID- 24312220
TI  - Inhibition of phosphatase and tensin homolog deleted on chromosome 10 decreases
      rat cortical neuron injury and blood-brain barrier permeability, and improves
      neurological functional recovery in traumatic brain injury model.
AB  - BACKGROUND AND PURPOSE: Recent evidence has supported the neuroprotective effect
      of bpV (pic), an inhibitor of phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN), in models of ischemic stroke. However, whether PTEN
      inhibitors improve long-term functional recovery after traumatic brain injury
      (TBI) and whether PTEN affects blood brain barrier (BBB) permeability need
      further elucidation. The present study was performed to address these issues.
      METHODS: Adult Sprague-Dawley rats were subjected to fluid percussion injury
      (FPI) after treatment with a well-established PTEN inhibitor bpV (pic) or saline
      starting 24 h before FPI. Western blotting, real-time quantitative PCR, or
      immunostaining was used to measure PTEN, p-Akt, or MMP-9 expression. We
      determined the presence of neuron apoptosis by TUNEL assay. Evans Blue dye
      extravasation was measured to evaluate the extent of BBB disruption. Functional
      recovery was assessed by the neurological severity score (NSS), and Kaplan-Meier
      analysis was used for survival analysis. RESULTS: PTEN expression was up
      regulated after TBI. After bpV (pic) treatment, p-Akt was also up-regulated. We
      found that bpV (pic) significantly decreased BBB permeability and reduced the
      number of TUNEL-positive cells. We further demonstrated that PTEN inhibition
      improved neurological function recovery in the early stage after TBI. CONCLUSION:
      These data suggest that treatment with the PTEN inhibitor bpV (pic) has a
      neuroprotective effect in TBI rats.

PMID- 24312221
TI  - Recrudescent infection supports Hendra virus persistence in Australian flying-fox
      populations.
AB  - Zoonoses from wildlife threaten global public health. Hendra virus is one of
      several zoonotic viral diseases that have recently emerged from Pteropus species
      fruit-bats (flying-foxes). Most hypotheses regarding persistence of Hendra virus
      within flying-fox populations emphasize horizontal transmission within local
      populations (colonies) via urine and other secretions, and transmission among
      colonies via migration. As an alternative hypothesis, we explore the role of
      recrudescence in persistence of Hendra virus in flying-fox populations via
      computer simulation using a model that integrates published information on the
      ecology of flying-foxes, and the ecology and epidemiology of Hendra virus.
      Simulated infection patterns agree with infection patterns observed in the field
      and suggest that Hendra virus could be maintained in an isolated flying-fox
      population indefinitely via periodic recrudescence in a manner indistinguishable
      from maintenance via periodic immigration of infected individuals. Further, post
      recrudescence pulses of infectious flying-foxes provide a plausible basis for the
      observed seasonal clustering of equine cases. Correct understanding of the
      infection dynamics of Hendra virus in flying-foxes is fundamental to effectively
      managing risk of infection in horses and humans. Given the lack of clear
      empirical evidence on how the virus is maintained within populations, the role of
      recrudescence merits increased attention. 

PMID- 24312222
TI  - Gonadotropin-releasing hormone for preservation of ovarian function during
      chemotherapy in lymphoma patients of reproductive age: a summary based on 434
      patients.
AB  - BACKGROUND: Gonadotropin-releasing hormone agonists (GnRHa) might play a role in
      preserving ovarian function in lymphoma patients by inhibiting chemotherapy
      induced ovarian follicular damage. However, studies of its clinical efficacy have
      reported conflicting results. METHOD: We conducted a meta-analysis to determine
      the effect of the preservation of ovarian function by administering GnRHa in
      young patients with lymphoma undergoing chemotherapy. Seven studies were
      identified that met inclusion criteria and comprised 434 patients assigned to
      GnRHa combined chemotherapy or chemotherapy alone. RESULTS: The incidence of
      women with premature ovarian failure (POF) demonstrated a statistically
      significant difference in favor of the use of GnRHa (OR=0.32, 95% CI 0.13-0.77).
      In addition, the final level of FSH in the GnRH group was significantly lower
      than control group. (MD= -11.73, 95% CI,-22.25- -1.20), and the final level of
      AMH in the GnRH group was significantly higher than control group (MD=0.80; 95%
      CI, 0.61-0.98). However, there was no statistically significant difference
      between treatment and the control groups in the incidence of a spontaneous
      pregnancy (OR=1.11; 95% CI, 0.55-2.26). CONCLUSION: This meta-analysis suggests
      that GnRHa may be effective in protecting ovarian function during chemotherapy in
      lymphoma patients. More well-designed prospective studies are needed to carry out
      for further understanding of this topic.

PMID- 24312223
TI  - Midgut microbial community of Culex quinquefasciatus mosquito populations from
      India.
AB  - The mosquito Culex quinquefasciatus is a ubiquitous species that serves as a
      major vector for west nile virus and lymphatic filariasis. Ingestion of bloodmeal
      by females triggers a series of physiological processes in the midgut and also
      exposes them to infection by these pathogens. The bacteria normally harbored in
      the midgut are known to influence physiology and can also alter the response to
      various pathogens. The midgut bacteria in female Cx. quinquefasciatus mosquitoes
      collected over a large geographical area from India was studied. Examination of
      16S ribosomal DNA amplicons from culturable microflora revealed the presence of
      83 bacterial species belonging to 31 bacterial genera. All of these species
      belong to three phyla i.e. Proteobacteria, Firmicutes and Actinobacteria. Phylum
      Proteobacteria was the most dominant phylum (37 species), followed by Firmicutes
      (33 species) and Actinobacteria (13 species). Phylum Proteobacteria, was
      dominated by members of gamma-proteobacteria class. The genus Staphylococcus was
      the largest genus represented by 11 species whereas Enterobacter was the most
      prevalent genus and recovered from all the field stations except Leh. Highest
      bacterial prevalence was observed from Bhuj (22 species) followed by Nagrota (18
      species), Masimpur (18 species) and Hathigarh (16 species). Whereas, least
      species were observed from Leh (8 species). It has been observed that individual
      mosquito harbor extremely diverse gut bacteria and have very small overlap
      bacterial taxa in their gut. This variation in midgut microbiota may be one of
      the factors responsible for variation in disease transmission rates or vector
      competence within mosquito population. The present data strongly encourage
      further investigations to verify the potential role of the detected bacteria in
      mosquito for the transmission of lymphatic filariasis and west nile virus. To the
      best of our knowledge this is the first study on midgut microbiota of wild Cx.
      quinquefasciatus from over a large geographical area. 

PMID- 24312224
TI  - Marine plastic pollution in waters around Australia: characteristics,
      concentrations, and pathways.
AB  - Plastics represent the vast majority of human-made debris present in the oceans.
      However, their characteristics, accumulation zones, and transport pathways remain
      poorly assessed. We characterised and estimated the concentration of marine
      plastics in waters around Australia using surface net tows, and inferred their
      potential pathways using particle-tracking models and real drifter trajectories.
      The 839 marine plastics recorded were predominantly small fragments
      ("microplastics", median length = 2.8 mm, mean length = 4.9 mm) resulting from
      the breakdown of larger objects made of polyethylene and polypropylene (e.g.
      packaging and fishing items). Mean sea surface plastic concentration was 4256.4
      pieces km(-2), and after incorporating the effect of vertical wind mixing, this
      value increased to 8966.3 pieces km(-2). These plastics appear to be associated
      with a wide range of ocean currents that connect the sampled sites to their
      international and domestic sources, including populated areas of Australia's east
      coast. This study shows that plastic contamination levels in surface waters of
      Australia are similar to those in the Caribbean Sea and Gulf of Maine, but
      considerably lower than those found in the subtropical gyres and Mediterranean
      Sea. Microplastics such as the ones described here have the potential to affect
      organisms ranging from megafauna to small fish and zooplankton.

PMID- 24312225
TI  - Estimating influenza deaths in Canada, 1992-2009.
AB  - BACKGROUND: Poisson regression modelling has been widely used to estimate the
      disease burden attributable to influenza, though not without concerns that some
      of the excess burden could be due to other causes. This study aims to provide
      annual estimates of the mortality and hospitalization burden attributable to both
      seasonal influenza and the 2009 A/H1N1 pandemic influenza for Canada, and to
      discuss issues related to the reliability of these estimates. METHODS: Weekly
      time-series for all-cause mortality and regression models were used to estimate
      the number of deaths in Canada attributable to influenza from September 1992 to
      December 2009. To assess their robustness, the annual estimates derived from
      different parameterizations of the regression model for all-cause mortality were
      compared. In addition, the association between the annual estimates for mortality
      and hospitalization by age group, underlying cause of death or primary reason for
      admission and discharge status is discussed. RESULTS: The crude influenza
      attributed mortality rate based on all-cause mortality and averaged over 17
      influenza seasons prior to the 2009 A/H1N1 pandemic was 11.3 (95%CI, 10.5 - 12.1)
      deaths per 100 000 population per year, or an average of 3,500 (95%CI, 3,200 -
      3,700) deaths per year attributable to seasonal influenza. The estimated annual
      rates ranged from undetectable at the ecological level to more than 6000 deaths
      per year over the three A/Sydney seasons. In comparison, we attributed an
      estimated 740 deaths (95%CI, 350-1500) to A(H1N1)pdm09. Annual estimates from
      different model parameterizations were strongly correlated, as were estimates for
      mortality and morbidity; the higher A(H1N1)pdm09 burden in younger age groups was
      the most notable exception. INTERPRETATION: With the exception of some of the
      Serfling models, differences in the ecological estimates of the disease burden
      attributable to influenza were small in comparison to the variation in disease
      burden from one season to another.

PMID- 24312226
TI  - Establishment of the relationship between tumor size and range of histological
      involvement to evaluate the rationality of current retinoblastoma management.
AB  - PURPOSE: To determine whether tumor size correlates with histopathological
      involvement and hence evaluate the rationality of conservative treatment for
      retinoblastoma. METHODS: We retrospectively studied 221 patients (221 eyes)
      treated for retinoblastoma with enucleation in the Zhongshan Ophthalmic Center of
      Sun Yat-sen University, China, from October 1995 to December 2004.
      Histopathological data included involvement of the anterior chamber, sclera,
      choroids, and optic nerve. Tumor size was measured by B-ultrasound examination.
      RESULTS: Tumor invasion of the optic nerve correlated with the Reese-Ellsworth (R
      E) staging system and the International Classification for Retinoblastoma (ICRB):
      optic nerve involvement was significantly more frequent in R-E stage V (P =
      0.009) and ICRB Group E (P = 0.002) cases. However, 19.1% of patients with R-E
      stage I, II and III, and 16.7% of patients with ICRB Group B and C disease showed
      histopathological involvement of the postlaminar optic nerve. Extraocular
      involvement was observed in 17.7% of tumors <= 15 mm in diameter. Tumors >15 mm
      in diameter showed greater extraocular involvement, including the optic nerve (P
      = 0.000) and sclera (P = 0.032), than tumors <= 15 mm in diameter. Postlaminar
      optic nerve invasion was observed in 19.6% of tumors <= 10 mm in thickness.
      Tumors >10 mm in thickness had sclera involvement more frequently than tumors <=
      10 mm in thickness (P = 0.029). Postlaminar optic nerve invasion was noted in
      17.1% of patients with tumors <= 15 mm in diameter and <= 10 mm in thickness.
      CONCLUSIONS: Medium-sized retinoblastomas frequently invade outside the globe.
      Thus, indications for conservative treatment need improvement.

PMID- 24312228
TI  - Butyrylcholinesterase genetic variants: association with cocaine dependence and
      related phenotypes.
AB  - OBJECTIVE: The search for genetic vulnerability factors in cocaine dependence has
      focused on the role that neuroplasticity plays in addiction. However, like many
      other drugs, the ability of an individual to metabolize cocaine can also
      influence susceptibility to dependence. Butyrylcholinesterase (BChE) metabolizes
      cocaine, and genetic variants of the BChE gene (BCHE) alter its catalytic
      activity. Therefore, we hypothesize that cocaine users with polymorphisms in BCHE
      can show diverse addictive behaviors due to differences in effective plasma
      concentrations of cocaine. Those polymorphisms might also influence users to
      prefer one of the two main preparations (crack or powder cocaine), despite having
      equal access to both. The present work investigates polymorphisms in BCHE and if
      those genetic variants constitute risk factors for cocaine dependence and for
      crack cocaine use. METHODS: A total of 1,436 individuals (698 cocaine-dependent
      patients and 738 controls) were genotyped for three single nucleotide
      polymorphisms (SNPs) in BCHE: rs1803274, rs4263329, and rs4680662. RESULTS: For
      rs4263329, a nominal difference was found between cases and controls. For
      rs1803274 (the functional SNP), a statistically significant difference was found
      between patients who used crack cocaine exclusively and those who used only
      powder cocaine (P = 0.027; OR = 4.36; 95% CI = 1.18-16.04). Allele frequencies
      and genotypes related to other markers did not differ between cases and controls
      or between the two cocaine subgroups. CONCLUSIONS: Our findings suggest that the
      AA genotype of rs1803274 is a risk factor for crack cocaine use, which is more
      addictive than powder cocaine use. Further studies are needed in order to confirm
      this preliminary result and clarify the role of BCHE and its variants in cocaine
      dependence.

PMID- 24312227
TI  - Mutation of Elfn1 in mice causes seizures and hyperactivity.
AB  - A growing number of proteins with extracellular leucine-rich repeats (eLRRs) have
      been implicated in directing neuronal connectivity. We previously identified a
      novel family of eLRR proteins in mammals: the Elfns are transmembrane proteins
      with 6 LRRs, a fibronectin type-3 domain and a long cytoplasmic tail. The recent
      discovery that Elfn1 protein, expressed postsynaptically, can direct the
      elaboration of specific electrochemical properties of synapses between particular
      cell types in the hippocampus strongly reinforces this hypothesis. Here, we
      present analyses of an Elfn1 mutant mouse line and demonstrate a functional
      requirement for this gene in vivo. We first carried out detailed expression
      analysis of Elfn1 using a beta-galactosidase reporter gene in the knockout line.
      Elfn1 is expressed in distinct subsets of interneurons of the hippocampus and
      cortex, and also in discrete subsets of cells in the habenula, septum, globus
      pallidus, dorsal subiculum, amygdala and several other regions. Elfn1 is
      expressed in diverse cell types, including local GABAergic interneurons as well
      as long-range projecting GABAergic and glutamatergic neurons. Elfn1 protein
      localises to axons of excitatory neurons in the habenula, and long-range
      GABAergic neurons of the globus pallidus, suggesting the possibility of
      additional roles for Elfn1 in axons or presynaptically. While gross anatomical
      analyses did not reveal any obvious neuroanatomical abnormalities, behavioural
      analyses clearly illustrate functional effects of Elfn1 mutation. Elfn1 mutant
      mice exhibit seizures, subtle motor abnormalities, reduced thigmotaxis and
      hyperactivity. The hyperactivity is paradoxically reversible by treatment with
      the stimulant amphetamine, consistent with phenotypes observed in animals with
      habenular lesions. These analyses reveal a requirement for Elfn1 in brain
      function and are suggestive of possible relevance to the etiology and
      pathophysiology of epilepsy and attention-deficit hyperactivity disorder.

PMID- 24312229
TI  - Further evidence of emotional allodynia in unmedicated young adults with major
      depressive disorder.
AB  - BACKGROUND: Recent evidence suggests that sensitivity to the emotional sequela of
      experimental thermal pain(measured by emotional unpleasantness) is heightened in
      individuals with major depressive disorder(MDD), a phenomenon we termed
      "emotional allodynia". The aim of this study was to examine whether acute happy
      and sad mood induction alters emotional allodynia in MDD. We hypothesized that
      emotional allodynia will be a robust characteristic of individuals with MDD
      compared to healthy controls. Thus, it would remain following acute mood
      induction, independent of valence. METHODS: Twenty-one subjects with current MDD
      and 21 well-matched healthy subjects(HC) received graded brief temperature
      stimuli following happy and sad mood inductions procedures(MIP). All subjects
      rated the intensity and affect(pleasantness/unpleasantness) of each stimulus.
      Sensory(pain intensity) and affective(pain unpleasantness) thresholds were
      determined by methods of constant stimuli. RESULTS: The MIPs reliably induced
      happy and sad mood and the resulting induced mood and subjective arousal were not
      different between the groups at the time of temperature stimulation. Compared to
      HC, MDD individuals demonstrated emotional allodynia. We found significantly
      decreased affective pain thresholds whereby significantly lower temperatures
      became unpleasant in the MDD compared to the HC group. This was not observed for
      the sensory pain thresholds. Within the MDD, the affective pain thresholds were
      significantly lower than the corresponding pain intensity thresholds, whereby non
      painful temperatures were already unpleasant for the MDD irrespective of the
      induced mood. This was not observed for the HC groups where the affective and
      pain intensity thresholds were comparable. CONCLUSIONS: These findings suggest
      that emotional allodynia may be a chronic characteristic of current MDD. Future
      studies should determine if emotional allodynia persists after psychological or
      pharmacological interventions. Finally, longitudinal work should examine whether
      emotional allodynia is a result of or vulnerability for depression and the role
      it plays in the increased susceptibility for pain complaints in this disorder.

PMID- 24312230
TI  - Stress and reproductive hormones in grizzly bears reflect nutritional benefits
      and social consequences of a salmon foraging niche.
AB  - Physiological indicators of social and nutritional stress can provide insight
      into the responses of species to changes in food availability. In coastal British
      Columbia, Canada, grizzly bears evolved with spawning salmon as an abundant but
      spatially and temporally constrained food source. Recent and dramatic declines in
      salmon might have negative consequences on bear health and ultimately fitness. To
      examine broadly the chronic endocrine effects of a salmon niche, we compared
      cortisol, progesterone, and testosterone levels in hair from salmon-eating bears
      from coastal BC (n = 75) with the levels in a reference population from interior
      BC lacking access to salmon (n = 42). As predicted, testosterone was higher in
      coastal bears of both sexes relative to interior bears, possibly reflecting
      higher social density on the coast mediated by salmon availability. We also
      investigated associations between the amount of salmon individual bears consumed
      (as measured by stable isotope analysis) and cortisol and testosterone in hair.
      Also as predicted, cortisol decreased with increasing dietary salmon and was
      higher after a year of low dietary salmon than after a year of high dietary
      salmon. These findings at two spatial scales suggest that coastal bears might
      experience nutritional or social stress in response to on-going salmon declines,
      providing novel insights into the effects of resource availability on fitness
      related physiology.

PMID- 24312231
TI  - Evolution of zygotic linkage disequilibrium in a finite local population.
AB  - One crucial feature of zygotic linkage disequilibrium (LD) analysis is its direct
      use of diploid genotyping data, irrespective of the type of mating system.
      Previous theories from an evolutionary perspective mainly focus on gametic LD,
      but the equivalent development for zygotic LD is not available. Here I study the
      evolution of zygotic LD and the covariances between gametic and zygotic LDs or
      between distinct zygotic LDs in a finite local population under constant
      immigration from a continent population. I derive the analytical theory under
      genetic hitchhiking effects or in a neutral process. Results indicate that
      zygotic LDs (diploid level) are more informative than gametic LD (haploid level)
      in indicating the effects of different evolutionary forces. Zygotic LDs may be
      greater than or comparable to gametic LD under the epistatic selection process,
      but smaller than gametic LD under the non epistatic selection process. The
      covariances between gametic and zygotic LDs are strongly affected by the mating
      system, linkage distance, and genetic drift effects, but weakly affected by seed
      and pollen flow and natural selection. The covariances between different zygotic
      LDs are generally robust to the effects of gene flow, selection, and linkage
      distance, but sensitive to the effects of genetic drift and mating system.
      Consistent patterns exist for the covariances between the zygotic LDs for the two
      locus genotypes with one common genotype at one locus or without any common
      genotype at each locus. The results highlight that zygotic LDs can be applied to
      detecting natural population history. 

PMID- 24312232
TI  - A new specific succinate-glutamate metabolomic hallmark in SDHx-related
      paragangliomas.
AB  - Paragangliomas (PGLs) are frequently associated with germline mutations in genes
      involved in energy metabolism. The purpose of the present study was to assess
      whether the tumor metabolomic profile of patients with hereditary and apparently
      sporadic PGLs enables the distinction of different subtypes of tumors. Twenty
      eight unrelated patients with a histological diagnosis of PGLs were included in
      the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD),
      6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients
      (one per patient) were evaluated with (1)H high-resolution magic angle spinning
      (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase
      in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and
      p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower
      values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007
      vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also
      exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were
      found to have the highest values of glutathione (GSH) compared to other tumors.
      Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were
      accurately distinguished from the other ones on both 3- and 2-class PLS-DA
      models. The present study shows that HRMAS NMR spectroscopy is a very promising
      method for investigating the metabolomic profile of various PGLs. The present
      data suggest the existence of a specific succinate-glutamate hallmark of SDHx
      PGLs. The relevance of such a metabolomic hallmark is expected to be very useful
      in designing novel treatment options as well as improving the diagnosis and
      follow-up of these tumors, including metastatic ones.

PMID- 24312233
TI  - A new oviraptorosaur (Dinosauria: Oviraptorosauria) from the late cretaceous of
      southern China and its paleoecological implications.
AB  - A new oviraptorosaur Nankangia jiangxiensis gen. et sp. nov. is described on the
      basis of a partial postcranial skeleton with a partial lower jaw collected from
      the Upper Cretaceous Nanxiong Formation of Ganzhou, in Jiangxi Province of
      southern China. The new taxon is diagnosed by: (1) a mandibular symphysis that is
      not turned down; (2) neural spines of the cranial caudal vertebrae that are wider
      transversely than anteroposteriorly, forming a large posterior fossa with rugose
      central areas; (3) a femoral neck extending at an angle of about 90 to the shaft;
      and (4) a ratio of femur to tibia length of 0.95. Phylogenetic analysis recovers
      Nankangia as basal to the oviraptorid Yulong, but more derived than Caenagnathus,
      which also has a mandibular symphysis that is not turned down. The coexistence of
      Nankangia jiangxiensis, Ganzhousaurus nankangensis, Jiangxisaurus ganzhouensis,
      an unnamed oviraptorid from Nanxiong Basin and Banji long suggests that they
      occupied distinct ecological niches. Nankangia may have been more herbivorous
      than carnivorous. 

PMID- 24312234
TI  - Geometric morphometrics of rodent sperm head shape.
AB  - Mammalian spermatozoa, particularly those of rodent species, are extremely
      complex cells and differ greatly in form and dimensions. Thus, characterization
      of sperm size and, particularly, sperm shape represents a major challenge. No
      consensus exists on a method to objectively assess size and shape of spermatozoa.
      In this study we apply the principles of geometric morphometrics to analyze
      rodent sperm head morphology and compare them with two traditional morphometry
      methods, that is, measurements of linear dimensions and dimensions-derived
      parameters calculated using formulae employed in sperm morphometry assessments.
      Our results show that geometric morphometrics clearly identifies shape
      differences among rodent spermatozoa. It is also capable of discriminating
      between size and shape and to analyze these two variables separately. Thus, it
      provides an accurate method to assess sperm head shape. Furthermore, it can
      identify which sperm morphology traits differ between species, such as the
      protrusion or retraction of the base of the head, the orientation and relative
      position of the site of flagellum insertion, the degree of curvature of the hook,
      and other distinct anatomical features and appendices. We envisage that the use
      of geometric morphometrics may have a major impact on future studies focused on
      the characterization of sperm head formation, diversity of sperm head shape among
      species (and underlying evolutionary forces), the effects of reprotoxicants on
      changes in cell shape, and phenotyping of genetically-modified individuals. 

PMID- 24312235
TI  - Time frame and justice motive: future perspective moderates the adaptive function
      of general belief in a just world.
AB  - BACKGROUND: The human ability to envision the future, that is, to take a future
      perspective (FP), plays a key role in the justice motive and its function in
      transcending disadvantages and misfortunes. The present research investigated
      whether individual (Study 1) and situational (Study 2) differences in FP
      moderated the association of general belief in a just world (GBJW) with
      psychological resilience. METHODOLOGY/PRINCIPAL FINDINGS: We investigated FP,
      GBJW, and resilience in sample of adolescents (n = 223) and disaster survivors (n
      = 218) in China. In Study 1, adolescents revealed stronger GBJW than PBJW, and
      GBJW uniquely predicted resilience in the daily lives of those with high FP (but
      not those with low FP). In Study 2, natural priming of FP (vs. no FP) facilitated
      the association of GBJW with resilience after disaster. CONCLUSIONS/SIGNIFICANCE:
      Supporting predictions, participants endorsed GBJW more strongly than PBJW.
      Further, GBJW interacted with FP in both studies, such that there was an
      association between GBJW and resilience at high but not low levels of FP. The
      results corroborate recent findings suggesting that GBJW may be more
      psychologically adaptive than PBJW among some populations. They also confirm that
      focusing on the future is an important aspect of the adaptive function of just
      world beliefs.

PMID- 24312236
TI  - Will you accept the government's friend request? Social networks and privacy
      concerns.
AB  - Participating in social network websites entails voluntarily sharing private
      information, and the explosive growth of social network websites over the last
      decade suggests shifting views on privacy. Concurrently, new anti-terrorism laws,
      such as the USA Patriot Act, ask citizens to surrender substantial claim to
      privacy in the name of greater security. I address two important questions
      regarding individuals' views on privacy raised by these trends. First, how does
      prompting individuals to consider security concerns affect their views on
      government actions that jeopardize privacy? Second, does the use of social
      network websites alter the effect of prompted security concerns? I posit that
      prompting individuals to consider security concerns does lead to an increased
      willingness to accept government actions that jeopardize privacy, but that
      frequent users of websites like Facebook are less likely to be swayed by prompted
      security concerns. An embedded survey experiment provides support for both parts
      of my claim. 

PMID- 24312237
TI  - Vitamin D status during pregnancy and the risk of subsequent postpartum
      depression: a case-control study.
AB  - Epidemiological studies have provided evidence of an association between vitamin
      D insufficiency and depression and other mood disorders, and a role for vitamin D
      in various brain functions has been suggested. We hypothesized that low vitamin D
      status during pregnancy might increase the risk of postpartum depression (PPD).
      The objective of the study was thus to determine whether low vitamin D status
      during pregnancy was associated with postpartum depression. In a case-control
      study nested in the Danish National Birth Cohort, we measured late pregnancy
      serum concentrations of 25[OH]D3 in 605 women with PPD and 875 controls. Odds
      ratios [OR) for PPD were calculated for six levels of 25[OH]D3. Overall, we found
      no association between vitamin D concentrations and risk of PPD (p = 0.08).
      Compared with women with vitamin D concentrations between 50 and 79 nmol/L, the
      adjusted odds ratios for PPD were 1.35 (95% CI: 0.64; 2.85), 0.83 (CI: 0.50;
      1.39) and 1.13 (CI: 0.84; 1.51) among women with vitamin D concentrations < 15
      nmol/L, 15-24 nmol/L and 25-49 nmol/L, respectively, and 1.53 (CI: 1.04; 2.26)
      and 1.89 (CI: 1.06; 3.37) among women with vitamin D concentrations of 80-99
      nmol/L and >= 100 nmol/L, respectively. In an additional analysis among women
      with sufficient vitamin D (>= 50 nmol/L), we observed a significant positive
      association between vitamin D concentrations and PPD. Our results did not support
      an association between low maternal vitamin D concentrations during pregnancy and
      risk of PPD. Instead, an increased risk of PPD was found among women with the
      highest vitamin D concentrations. 

PMID- 24312239
TI  - Pup mortality in a rapidly declining harbour seal (Phoca vitulina) population.
AB  - The harbour seal population in Orkney, off the north coast of Scotland, has
      reduced by 65% between 2001 and 2010. The cause(s) of this decline are unknown
      but must affect the demographic parameters of the population. Here, satellite
      telemetry data were used to test the hypothesis that increased pup mortality
      could be a primary driver of the decline in Orkney. Pup mortality and tag failure
      parameters were estimated from the duration of operation of satellite tags
      deployed on harbour seal pups from the Orkney population (n = 24) and from
      another population on the west coast of Scotland (n = 24) where abundance was
      stable. Survival probabilities from both populations were best represented by a
      common gamma distribution and were not different from one another, suggesting
      that increased pup mortality is unlikely to be the primary agent in the Orkney
      population decline. The estimated probability of surviving to 6 months was 0.390
      (95% CI 0.297 - 0.648) and tag failure was represented by a Gaussian
      distribution, with estimated mean 270 (95% CI = 198 - 288) and s.d. 21 (95% CI =
      1 - 66) days. These results suggest that adult survival is the most likely
      proximate cause of the decline. They also demonstrate a novel technique for
      attaining age-specific mortality rates from telemetry data.

PMID- 24312238
TI  - Production of hybrid-IgG/IgA plantibodies with neutralizing activity against
      Shiga toxin 1.
AB  - Shiga toxin 1 (Stx1) is a virulence factor of enterohemorrhagic Escherichia coli,
      such as the O157:H7 strain. In the intestines, secretory IgA (SIgA) is a major
      component of the immune defense against pathogens and toxins. To form SIgA, the
      production of dimeric IgA that retains biological activity is an important step.
      We previously established hybrid-IgG/IgA having variable regions of the IgG
      specific for the binding subunit of Stx1 (Stx1B) and the heavy chain constant
      region of IgA. If hybrid-IgG/IgA cDNAs can be expressed in plants, therapeutic or
      preventive effects may be expected in people eating those plants containing a
      "plantibody". Here, we established transgenic Arabidopsis thaliana expressing
      dimeric hybrid-IgG/IgA. The heavy and light chain genes were placed under the
      control of a bidirectional promoter and terminator of the chlorophyll a/b-binding
      protein of Arabidopsis thaliana (expression cassette). This expression cassette
      and the J chain gene were subcloned into a single binary vector, which was then
      introduced into A. thaliana by means of the Agrobacterium method. Expression and
      assembly of the dimeric hybrid-IgG/IgA in plants were revealed by ELISA and
      immunoblotting. The hybrid-IgG/IgA bound to Stx1B and inhibited Stx1B binding to
      Gb3, as demonstrated by ELISA. When Stx1 holotoxin was pre-treated with the
      resulting plantibody, the cytotoxicity of Stx1 was inhibited. The toxin
      neutralization was also demonstrated by means of several assays including Stx1
      induced phosphatidylserine translocation on the plasma membrane, caspase-3
      activation and 180 base-pair DNA ladder formation due to inter-nucleosomal
      cleavage. These results indicate that edible plants containing hybrid-IgG/IgA
      against Stx1B have the potential to be used for immunotherapy against Stx1-caused
      food poisoning. 

PMID- 24312240
TI  - Planning steps forward in development: in girls earlier than in boys.
AB  - The development of planning ability in children initially aged four and five was
      examined longitudinally with a retest-interval of 12 months using the Tower of
      London task. As expected, problems to solve straightforward without mental look
      ahead were mastered by most, even the youngest children. Problems demanding look
      ahead were more difficult and accuracy improved significantly with age and over
      time. This development was strongly moderated by sex: In contrast to coeval boys,
      four year old girls showed an impressive performance enhancement at age five,
      reaching the performance of six year olds, whereas four year old boys lagged
      behind and caught up with girls at the age of six, the typical age of school
      enrollment. This sex-specific development of planning was clearly separated from
      overall intelligence: young boys showed a steeper increase in raw intelligence
      scores than girls, whereas in the older groups scores developed similarly. The
      observed sex differences in planning development are evident even within a narrow
      time window of twelve months and may relate to differences in maturational
      trajectories for girls and boys in dorsolateral prefrontal cortex. 

PMID- 24312241
TI  - Catheter ablation of idiopathic premature ventricular contractions and
      ventricular tachycardias originating from the vicinity of endocardial and
      epicardial mitral annulus.
AB  - BACKGROUND: Several previous reports have revealed that idiopathic ventricular
      arrhythmias (VAs), including premature ventricular contractions (PVCs) and
      ventricular tachycardias (IVTs), can originate from endocardial mitral annulus
      (ENDO MA). However, these data are limited to ENDO MA VAs, and little is known
      about the electrocardiographic (ECG) characteristics and the efficacy of
      radiofrequency catheter ablation (RFCA) via the coronary venous system for the
      VAs arising from the epicardial MA (EPI MA). METHODOLOGY/PRINCIPAL FINDINGS:
      Characteristics of body surface electrocardiogram and electrophysiologic
      recordings were analyzed in 21 patients with symptomatic PVCs/IVTs originating
      from the vicinity of MA. Among 597 patients with PVCs/IVTs, the incidence of VAs
      originating from the ENDO and EPI MA was 3.52% (21 cases). Eleven (52%) from the
      ENDO MA, and 10 (48%) from the EPI MA. There were different characteristics of
      ECG of PVCs/VT originating from the ENDO and EPI MA. The prolonged pseudodelta
      wave time and intrinsicoid deflection time in lead V2 and the precordial maximum
      deflection index reliably differentiated EPI MA VAs from ENDO MA VAs with high
      sensitivity and specificity. Successful RFCA in 18 patients could be achieved
      (85.7% acute procedural success). CONCLUSIONS/SIGNIFICANCE: ECG characteristics
      of PVCs/VTs originating from the different portions of the MA are different, and
      can help regionalize the origin of these arrhythmias. RFCA within the coronary
      venous system was relatively effective and safe for the PVCs/IVTs and should be
      seen as an alternative approach, when the MA PVCs/IVTs could not be eliminated by
      RFCA from the endocardium.

PMID- 24312243
TI  - Lead us not into tanktation: a simulation modelling approach to gain insights
      into incentives for sporting teams to tank.
AB  - Annual draft systems are the principal method used by teams in major sporting
      leagues to recruit amateur players. These draft systems frequently take one of
      three forms: a lottery style draft, a weighted draft, or a reverse-order draft.
      Reverse-order drafts can create incentives for teams to deliberately under
      perform, or tank, due to the perceived gain from obtaining quality players at
      higher draft picks. This paper uses a dynamic simulation model that captures the
      key components of a win-maximising sporting league, including the amateur player
      draft, draft choice error, player productivity, and between-team competition, to
      explore how competitive balance and incentives to under-perform vary according to
      league characteristics. We find reverse-order drafts can lead to some teams
      cycling between success and failure and to other teams being stuck in mid-ranking
      positions for extended periods of time. We also find that an incentive for teams
      to tank exists, but that this incentive decreases (i) as uncertainty in the
      ability to determine quality players in the draft increases, (ii) as the number
      of teams in the league reduces, (iii) as team size decreases, and (iv) as the
      number of teams adopting a tanking strategy increases. Simulation models can be
      used to explore complex stochastic dynamic systems such as sports leagues, where
      managers face difficult decisions regarding the structure of their league and the
      desire to maintain competitive balance. 

PMID- 24312242
TI  - Stage-specific inhibition of TrkB activity leads to long-lasting and sexually
      dimorphic effects on body weight and hypothalamic gene expression.
AB  - During development, prenatal and postnatal factors program homeostatic set points
      to regulate food intake and body weight in the adult. Combinations of genetic and
      environmental factors contribute to the development of neural circuitry that
      regulates whole-body energy homeostasis. Brain-derived neurotrophic factor (Bdnf)
      and its receptor, Tyrosine kinase receptor B (TrkB), are strong candidates for
      mediating the reshaping of hypothalamic neural circuitry, given their well
      characterized role in the central regulation of feeding and body weight. Here, we
      employ a chemical-genetic approach using the TrkB(F616A/F616A) knock-in mouse
      model to define the critical developmental period in which TrkB inhibition
      contributes to increased adult fat mass. Surprisingly, transient TrkB inhibition
      in embryos, preweaning pups, and adults all resulted in long-lasting increases in
      body weight and fat content. Moreover, sex-specific differences in the effects of
      TrkB inhibition on both body weight and hypothalamic gene expression were
      observed at multiple developmental stages. Our results highlight both the
      importance of the Bdnf/TrkB pathway in maintaining normal body weight throughout
      life and the role of sex-specific differences in the organization of hypothalamic
      neural circuitry that regulates body weight. 

PMID- 24312244
TI  - Associations between parent-adolescent attachment relationship quality, negative
      life events and mental health.
AB  - PURPOSE: The aim of this study was to examine the association of negative life
      events and parent-adolescent attachment relationship quality with mental health
      problems and to explore an interaction between the parent-adolescent attachment
      relationship and one or multiple negative life events on the mental health of
      adolescents. METHODS: A two-year longitudinal study was conducted among first
      year secondary school students (N = 3181). The occurrence of life events and the
      quality of parent-adolescent attachment were assessed at baseline and mental
      health status at two-year follow-up by means of self-report questionnaires.
      Binary logistic regression analyses were conducted to assess associations between
      life events, parent-adolescent attachment and mental health problems. Relative
      Excess Risk due to Interaction techniques were used to determine the interaction
      effects on the additive scale. RESULTS: Life events were related to mental health
      status, as was parent-adolescent attachment. The combined effect of an
      unfavourable parent-adolescent attachment with life events on mental health was
      larger than the sum of the two individual effects. Among adolescents with one
      life event or multiple life events, an unfavourable parent-adolescent attachment
      increased the risk of mental health problems at follow-up compared to the group
      without life events. CONCLUSION: Results supported an interaction effect between
      parent-adolescent attachment and negative life events on mental health.
      Especially adolescents with one or multiple life events and an unfavourable
      parent-adolescent attachment seems to be a vulnerable group for mental health
      problems. Implications for further research are discussed.

PMID- 24312245
TI  - Silencing of long noncoding RNA AK139328 attenuates ischemia/reperfusion injury
      in mouse livers.
AB  - Recently, increasing evidences had suggested that long noncoding RNAs (LncRNAs)
      are involved in a wide range of physiological and pathophysiological processes.
      Here we determined the LncRNA expression profile using microarray technology in
      mouse livers after ischemia/reperfusion treatment. Seventy one LncRNAs were
      upregulated, and 27 LncRNAs were downregulated in ischemia/reperfusion-treated
      mouse livers. Eleven of the most significantly deregulated LncRNAs were further
      validated by quantitative PCR assays. Among the upregulated LncRNAs confirmed by
      quantitative PCR assays, AK139328 exhibited the highest expression level in
      normal mouse livers. siRNA-mediated knockdown of hepatic AK139328 decreased
      plasma aminotransferase activities, and reduced necrosis area in the livers with
      a decrease in caspase-3 activation after ischemia/reperfusion treatment. In
      ischemia/reperfusion liver, knockdown of AK139328 increased survival signaling
      proteins including phosphorylated Akt (pAkt), glycogen synthase kinase 3 (pGSK3)
      and endothelial nitric oxide synthase (peNOS). Furthermore, knockdown of AK139328
      also reduced macrophage infitration and inhibited NF-kappaB activity and
      inflammatory cytokines expression. In conclusion, these findings revealed that
      deregulated LncRNAs are involved in liver ischemia/reperfusion injury. Silencing
      of AK139328 ameliorated ischemia/reperfusion injury in the liver with the
      activation of Akt signaling pathway and inhibition of NF-kappaB activity. LncRNA
      AK139328 might be a novel target for diagnosis and treatment of liver surgery or
      transplantation. 

PMID- 24312246
TI  - PIIKA 2: an expanded, web-based platform for analysis of kinome microarray data.
AB  - Kinome microarrays are comprised of peptides that act as phosphorylation targets
      for protein kinases. This platform is growing in popularity due to its ability to
      measure phosphorylation-mediated cellular signaling in a high-throughput manner.
      While software for analyzing data from DNA microarrays has also been used for
      kinome arrays, differences between the two technologies and associated biologies
      previously led us to develop Platform for Intelligent, Integrated Kinome Analysis
      (PIIKA), a software tool customized for the analysis of data from kinome arrays.
      Here, we report the development of PIIKA 2, a significantly improved version with
      new features and improvements in the areas of clustering, statistical analysis,
      and data visualization. Among other additions to the original PIIKA, PIIKA 2 now
      allows the user to: evaluate statistically how well groups of samples cluster
      together; identify sets of peptides that have consistent phosphorylation patterns
      among groups of samples; perform hierarchical clustering analysis with
      bootstrapping; view false negative probabilities and positive and negative
      predictive values for t-tests between pairs of samples; easily assess
      experimental reproducibility; and visualize the data using volcano plots,
      scatterplots, and interactive three-dimensional principal component analyses.
      Also new in PIIKA 2 is a web-based interface, which allows users unfamiliar with
      command-line tools to easily provide input and download the results.
      Collectively, the additions and improvements described here enhance both the
      breadth and depth of analyses available, simplify the user interface, and make
      the software an even more valuable tool for the analysis of kinome microarray
      data. Both the web-based and stand-alone versions of PIIKA 2 can be accessed via
      http://saphire.usask.ca. 

PMID- 24312247
TI  - Phytoceramide in vertebrate tissues: one step chromatography separation for
      molecular characterization of ceramide species.
AB  - Ceramide is a precursor for complex sphingolipids in vertebrates, while plants
      contain phytoceramide. By using a novel chromatography purification method we
      show that phytoceramide comprises a significant proportion of animal
      sphingolipids. Total ceramide including phytoceramide from mouse tissue (brain,
      heart, liver) lipid extracts and cell culture (mouse primary astrocytes, human
      oligodendroglioma cells) was eluted as a single homogenous fraction, and then
      analyzed by thin layer chromatography, and further characterized by gas
      chromatography-mass spectrometry (GC-MS). We detected a unique band that migrated
      between non-hydroxy fatty acyl ceramide and hydroxy fatty acyl ceramide, and
      identified it as phytoceramide. Using RT-PCR, we confirmed that mouse tissues
      expressed desaturase 2, an enzyme that has been reported to generate
      phytoceramide from dihydroceramide. Previously, only trace amounts of
      phytoceramide were reported in vertebrate intestine, kidney, and skin. While its
      function is still elusive, this is the first report of phytoceramide
      characterization in glial cells and vertebrate brain, heart, and liver. 

PMID- 24312248
TI  - Transcription profiling reveals potential mechanisms of dysbiosis in the oral
      microbiome of rhesus macaques with chronic untreated SIV infection.
AB  - A majority of individuals infected with human immunodeficiency virus (HIV) have
      inadequate access to antiretroviral therapy and ultimately develop debilitating
      oral infections that often correlate with disease progression. Due to the
      impracticalities of conducting host-microbe systems-based studies in HIV infected
      patients, we have evaluated the potential of simian immunodeficiency virus (SIV)
      infected rhesus macaques to serve as a non-human primate model for oral
      manifestations of HIV disease. We present the first description of the rhesus
      macaque oral microbiota and show that a mixture of human commensal bacteria and
      "macaque versions" of human commensals colonize the tongue dorsum and dental
      plaque. Our findings indicate that SIV infection results in chronic activation of
      antiviral and inflammatory responses in the tongue mucosa that may collectively
      lead to repression of epithelial development and impact the microbiome. In
      addition, we show that dysbiosis of the lingual microbiome in SIV infection is
      characterized by outgrowth of Gemella morbillorum that may result from impaired
      macrophage function. Finally, we provide evidence that the increased capacity of
      opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated
      with reduced production of antimicrobial peptides. 

PMID- 24312249
TI  - Corporate philanthropy, political influence, and health policy.
AB  - BACKGROUND: The Framework Convention of Tobacco Control (FCTC) provides a basis
      for nation states to limit the political effects of tobacco industry
      philanthropy, yet progress in this area is limited. This paper aims to integrate
      the findings of previous studies on tobacco industry philanthropy with a new
      analysis of British American Tobacco's (BAT) record of charitable giving to
      develop a general model of corporate political philanthropy that can be used to
      facilitate implementation of the FCTC. METHOD: Analysis of previously
      confidential industry documents, BAT social and stakeholder dialogue reports, and
      existing tobacco industry document studies on philanthropy. RESULTS: The analysis
      identified six broad ways in which tobacco companies have used philanthropy
      politically: developing constituencies to build support for policy positions and
      generate third party advocacy; weakening opposing political constituencies;
      facilitating access and building relationships with policymakers; creating direct
      leverage with policymakers by providing financial subsidies to specific projects;
      enhancing the donor's status as a source of credible information; and shaping the
      tobacco control agenda by shifting thinking on the importance of regulating the
      market environment for tobacco and the relative risks of smoking for population
      health. Contemporary BAT social and stakeholder reports contain numerous examples
      of charitable donations that are likely to be designed to shape the tobacco
      control agenda, secure access and build constituencies. CONCLUSIONS AND
      RECOMMENDATIONS: Tobacco companies' political use of charitable donations
      underlines the need for tobacco industry philanthropy to be restricted via full
      implementation of Articles 5.3 and 13 of the FCTC. The model of tobacco industry
      philanthropy developed in this study can be used by public health advocates to
      press for implementation of the FCTC and provides a basis for analysing the
      political effects of charitable giving in other industry sectors which have an
      impact on public health such as alcohol and food.

PMID- 24312250
TI  - Adenosine A2A receptors in striatal glutamatergic terminals and GABAergic neurons
      oppositely modulate psychostimulant action and DARPP-32 phosphorylation.
AB  - Adenosine A2A receptors (A2AR) are located postsynaptically in striatopallidal
      GABAergic neurons, antagonizing dopamine D2 receptor functions, and are also
      located presynaptically at corticostriatal terminals, facilitating glutamate
      release. To address the hypothesis that these two A2AR populations differently
      control the action of psychostimulants, we characterized A2AR modulation of
      cocaine-induced effects at the level of DARPP-32 phosphorylation at Thr-34 and
      Thr-75, c-Fos expression, and psychomotor activity using two lines of cell-type
      selective A2AR knockout (KO) mice with selective A2AR deletion in GABAergic
      neurons (striatum-A2AR-KO mice), or with A2AR deletion in both striatal GABAergic
      neurons and projecting cortical glutamatergic neurons (forebrain-A2AR-KO mice).
      We demonstrated that striatum-A2AR KO mice lacked A2ARs exclusively in striatal
      GABAergic terminals whereas forebrain-A2AR KO mice lacked A2ARs in both striatal
      GABAergic and glutamatergic terminals leading to a blunted A2AR-mediated
      facilitation of synaptosomal glutamate release. The inactivation of A2ARs in
      GABAergic neurons reduced striatal DARPP-32 phosphorylation at Thr-34 and
      increased its phosphorylation at Thr-75. Conversely, the additional deletion of
      corticostriatal glutamatergic A2ARs produced opposite effects on DARPP-32
      phosphorylation at Thr-34 and Thr-75. This distinct modulation of DARPP-32
      phosphorylation was associated with opposite responses to cocaine-induced
      striatal c-Fos expression and psychomotor activity in striatum-A2AR KO (enhanced)
      and forebrain-A2AR KO mice (reduced). Thus, A2ARs in glutamatergic
      corticostriatal terminals and in GABAergic striatal neurons modulate the action
      of psychostimulants and DARPP-32 phosphorylation in opposite ways. We conclude
      that A2ARs in glutamatergic terminals prominently control the action of
      psychostimulants and define a novel mechanism by which A2ARs fine-tune striatal
      activity by integrating GABAergic, dopaminergic and glutamatergic signaling. 

PMID- 24312251
TI  - Resistance to degradation and cellular distribution are important features for
      the antitumor activity of gomesin.
AB  - Many reports have shown that antimicrobial peptides exhibit anticancer abilities.
      Gomesin (Gm) exhibits potent cytotoxic activity against cancer cells by a
      membrane pore formation induced after well-orchestrated intracellular mechanisms.
      In this report, the replacements of the Cys by Ser or Thr, and the use D-amino
      acids in the Gm structure were done to investigate the importance of the
      resistance to degradation of the molecule with its cytotoxicity. [Thr(2,6,11,15)]
      Gm, and [Ser(2,6,11,15)]-Gm exhibits low cytotoxicity, and low resistance to
      degradation, and after 24 h are present in localized area near to the membrane.
      Conversely, the use of D-amino acids in the analogue [D-Thr(2,6,11,15)]-D-Gm
      confers resistance to degradation, increases its potency, and maintained this
      peptide spread in the cytosol similarly to what happens with Gm. Replacements of
      Cys by Thr and Gln by L- or D-Pro ([D-Thr(2,6,11,15), Pro(9)]-D-Gm, and
      [Thr(2,6,11,15), D-Pro(9)]-Gm), which induced a similar beta-hairpin
      conformation, also increase their resistance to degradation, and cytotoxicity,
      but after 24 h they are not present spread in the cytosol, exhibiting lower
      cytotoxicity in comparison to Gm. Additionally, chloroquine, a lysosomal enzyme
      inhibitor potentiated the effect of the peptides. Furthermore, the binding and
      internalization of peptides was determined, but a direct correlation among these
      factors was not observed. However, cholesterol ablation, which increase fluidity
      of cellular membrane, also increase cytotoxicity and internalization of peptides.
      beta-hairpin spatial conformation, and intracellular localization/target, and the
      capability of entry are important properties of gomesin cytotoxicity. 

PMID- 24312252
TI  - Chimpanzees (Pan troglodytes) flexibly adjust their behaviour in order to
      maximize payoffs, not to conform to majorities.
AB  - Chimpanzees have been shown to be adept learners, both individually and socially.
      Yet, sometimes their conservative nature seems to hamper the flexible adoption of
      superior alternatives, even to the extent that they persist in using entirely
      ineffective strategies. In this study, we investigated chimpanzees' behavioural
      flexibility in two different conditions under which social animals have been
      predicted to abandon personal preferences and adopt alternative strategies: i)
      under influence of majority demonstrations (i.e. conformity), and ii) in the
      presence of superior reward contingencies (i.e. maximizing payoffs). Unlike
      previous nonhuman primate studies, this study disentangled the concept of
      conformity from the tendency to maintain one's first-learned strategy. Studying
      captive (n=16) and semi-wild (n=12) chimpanzees in two complementary exchange
      paradigms, we found that chimpanzees did not abandon their behaviour in order to
      match the majority, but instead remained faithful to their first-learned strategy
      (Study 1a and 1b). However, the chimpanzees' fidelity to their first-learned
      strategy was overridden by an experimental upgrade of the profitability of the
      alternative strategy (Study 2). We interpret our observations in terms of
      chimpanzees' relative weighing of behavioural options as a function of situation
      specific trade-offs. More specifically, contrary to previous findings,
      chimpanzees in our study abandoned their familiar behaviour to maximize payoffs,
      but not to conform to a majority. 

PMID- 24312253
TI  - Peer-based education and the integration of HIV and Sexual and Reproductive
      Health services for young people in Vietnam: evidence from a project evaluation.
AB  - INTRODUCTION: This paper reports changes in behavioral outcomes related to the
      use of HIV testing service of a project that employed peer-based education
      strategies and integration of HIV voluntary counseling and testing (VCT) and
      Sexual and Reproductive Health (SRH) services targeting young people aged 15-24
      across 5 provinces in Vietnam. METHODS: A pre-test/post-test, non-experimental
      evaluation design was used. Data were collected from cross-sectional surveys of
      youth and client exit interviews at project supported SRH clinics conducted at
      baseline and again at 24 months following implementation. The baseline samples
      consisted of 813 youth and 399 exit clients. The end line samples included 501
      youths and 399 exit clients. Z test was used to assess changes in behavioral
      outcomes. RESULTS: Results show that there was a significant increase (p<0.05) in
      the percentage of youth who wanted to obtain a HIV test (from 33% to 51%), who
      had ever had a test (from 7.5% to 15%), and who had a repeat test in the last 12
      months (from 54.5% to 67.5%). Exit client interviews found a nearly five-fold
      increase in the percentage of clients seeking HIV VCT in their current visit
      (5.0% vs. 24.5%) and almost two-fold increase in the percentage of those having
      their last test at a project supported clinic (9.3% vs. 17.8%). There were also
      positive changes in some aspects of youth HIV/AIDS knowledge, attitudes, and risk
      perceptions. CONCLUSIONS: This study provides preliminary evidence regarding the
      benefits of the integration of HIV VCT-SRH services in terms of increased access
      to HIV services and testing in Vietnam. Benefits of peer-based education
      regarding increased HIV knowledge were also identified. Further investigations,
      including experimental studies with assessment of health outcomes and the uptake
      of HIV testing services, are required to better elucidate the effectiveness and
      challenges of this intervention model in Vietnam.

PMID- 24312254
TI  - Phacoemulsification induced transient swelling of corneal Descemet's Endothelium
      Complex imaged with ultra-high resolution optical coherence tomography.
AB  - PURPOSE: Thickness changes of corneal sub-layers after phacoemulsification were
      investigated by spectral domain ultra-high resolution optical coherence
      tomography (UHR-OCT). METHODS: The corneas (n = 26) of 26 age-related cataract
      surgery patients were studied. UHR-OCT was used to evaluate the thickness of
      Descemet's Endothelium Complex (DEC), stroma, Bowman's layer, epithelium, and
      full cornea at the center (CCT) before, one day after, and one week after
      surgery. Non-contact specular microscopy measured CCT, endothelial cell density,
      and morphology. RESULTS: The DEC, stroma, Bowman's layer, and epithelium were
      visualized by UHR-OCT. Before surgery, the DEC in all cases appeared as a
      translucent space between two smooth opaque lines. One day after surgery, the
      posterior corneal surfaces in half of the eyes were wavy and irregular. Compared
      to the baseline, one day after surgery the thickness increases of the DEC,
      stroma, and CCT were 4.3 +/- 2.6 um, 25.5 +/- 24.9 um, and 32.1 +/- 26.6 um,
      respectively (P < 0.001). The morphology of the DEC and the CCT recovered to
      baseline one week after surgery (P > 0.05), but endothelial cell density was 8.7%
      less than at baseline. There were no significant changes in Bowman's layer and
      epithelium after the operation. The pre-operative DEC thickness was positively
      correlated with the decreased endothelial cell density at 1 day after surgery (r
      = 0.55, P = 0.003). CONCLUSIONS: The DEC showed edematous thickening and
      different degrees of morphological changes after phacoemulsification. The DEC
      deformation and corneal edema recovered by one week after surgery, which
      indicated recovery of endothelial function. UHR-OCT is a useful tool to evaluate
      function of the DEC after phacoemulsification. Pre-operative DEC thickness may
      indicate the integrity of the endothelium and could be used for predicting
      endothelial cell loss after phacoemulsification.

PMID- 24312255
TI  - Post-weaning diet affects faecal microbial composition but not selected adipose
      gene expression in the cat (Felis catus).
AB  - The effects of pre- (i.e., gestation and during lactation) and post-weaning diet
      on the composition of faecal bacterial communities and adipose expression of key
      genes in the glucose and insulin pathways were investigated in the cat. Queens
      were maintained on a moderate protein:fat:carbohydrate kibbled ("Diet A";
      35:20:28% DM; n  =  4) or high protein:fat:carbohydrate canned ("Diet B";
      45:37:2% DM; n = 3) diet throughout pregnancy and lactation. Offspring were
      weaned onto these diets in a nested design (n  =  5 per treatment). Faecal
      samples were collected at wk 8 and 17 of age. DNA was isolated from faeces and
      bacterial 16S rRNA gene amplicons were analysed by pyrosequencing. RNA was
      extracted from blood (wk 18) and adipose tissue and ovarian/testicular tissues
      (wk 24) and gene expression levels determined using RT-qPCR. Differences (P<0.05)
      in composition of faecal bacteria were observed between pregnant queens fed Diet
      A or B. However, pre-weaning diet had little effect on faecal bacterial
      composition in weaned kittens. In contrast, post-weaning diet altered bacterial
      population profiles in the kittens. Increased (P<0.05) abundance of Firmicutes
      (77% vs 52% of total reads) and Actinobacteria (0.8% vs 0.2% of total reads), and
      decreased (P<0.05) abundance of Fusobacteria (1.6% vs 18.4% of total reads) were
      observed for kittens fed the Diet A compared to those fed Diet B post-weaning.
      Feeding Diet B pre-weaning increased (P<0.05) the expression levels of INRS,
      LEPT, PAI-1 and tended to increase GLUT1, while the expression levels of IRS-1 in
      blood increased in kittens fed Diet A pre-weaning. Post-weaning diet had no
      effect on expression levels of target genes. Correlations between the expression
      levels of genes involved in glucose and insulin pathways and faecal Bacteriodetes
      and Firmicutes phyla were identified. The reasons for why post-weaning diet
      affects microbial populations and not gene expression levels are of interest.

PMID- 24312256
TI  - Molecular markers for granulovacuolar degeneration are present in rimmed
      vacuoles.
AB  - BACKGROUND: Rimmed vacuoles (RVs) are round-oval cytoplasmic inclusions, detected
      in muscle cells of patients with myopathies, such as inclusion body myositis
      (IBM) and distal myopathy with RVs (DMRV). Granulovacuolar degeneration (GVD)
      bodies are spherical vacuoles containing argentophilic and hematoxyphilic
      granules, and are one of the pathological hallmarks commonly found in hippocampal
      pyramidal neurons of patients with aging-related neurodegenerative diseases, such
      as Alzheimer's disease and Parkinson's disease. These diseases are common in the
      elderly and share some pathological features. Therefore, we hypothesized that
      mechanisms of vacuolar formation in RVs and GVD bodies are common despite their
      role in two differing pathologies. We explored the components of RVs by
      immunohistochemistry, using antibodies for GVD markers. METHODS: Subjects
      included one AD case, eight cases of sporadic IBM, and three cases of DMRV. We
      compared immunoreactivity and staining patterns for GVD markers. These markers
      included: (1) tau-modifying proteins (caspase 3, cyclin-dependent kinase 5
      [CDK5], casein kinase 1delta [CK1delta], and c-jun N-terminal kinase [JNK]), (2)
      lipid raft-associated materials (annexin 2, leucine-rich repeat kinase 2 [LRRK2],
      and flotillin-1), and (3) other markers (charged multi-vesicular body protein 2B
      [CHMP2B] and phosphorylated transactive response DNA binding protein-43 [pTDP43])
      in both GVD bodies and RVs. Furthermore, we performed double staining of each GVD
      marker with pTDP43 to verify the co-localization. RESULTS: GVD markers, including
      lipid raft-associated proteins and tau kinases, were detected in RVs. CHMP2B,
      pTDP43, caspase 3, LRRK2, annexin 2 and flotillin-1 were detected on the rim and
      were diffusely distributed in the cytoplasm of RV-positive fibers. CDK5, CK1delta
      and JNK were detected only on the rim. In double staining experiments, all GVD
      markers colocalized with pTDP43 in RVs. CONCLUSIONS: These results suggest that
      RVs of muscle cells and GVD bodies of neurons share a number of molecules, such
      as raft-related proteins and tau-modifying proteins.

PMID- 24312257
TI  - The Ca2+-activated K+ channel KCa3.1 as a potential new target for the prevention
      of allograft vasculopathy.
AB  - Allograft vasculopathy (AV) remains one of the major challenges to the long-term
      functioning of solid organ transplants. Although its exact pathogenesis remains
      unclear, AV is characterized by both fibromuscular proliferation and infiltration
      of CD4(+) memory T cells. We here tested whether two experimental
      immunosuppressants targeting K(+) channels might be useful for preventing AV. PAP
      1 inhibits the voltage-gated Kv1.3 channel, which is overexpressed on CCR7(-)
      memory T cells and we therefore hypothesize that it should suppress the memory T
      cell component of AV. Based on its previous efficacy in restenosis and kidney
      fibrosis we expected that the KCa3.1 blocker TRAM-34 would primarily affect
      smooth muscle and fibroblast proliferation and thus reduce intimal hyperplasia.
      Using immunohistochemistry we demonstrated the presence of Kv1.3 on infiltrating
      T cells and of KCa3.1 on lymphocytes as well as on proliferating neointimal
      smooth muscle cells in human vasculopathy samples and in a rat aorta transplant
      model developing chronic AV. Treatment of PVG rats receiving orthotopically
      transplanted aortas from ACI rats with TRAM-34 dose-dependently reduced aortic
      luminal occlusion, intimal hyperplasia, mononuclear cell infiltration and
      collagen deposition 120 days after transplantation. The Kv1.3 blocker PAP-1 in
      contrast did not reduce intima hyperplasia despite drastically reducing plasma
      IFN-gamma levels and inhibiting lymphocyte infiltration. Our findings suggest
      that KCa3.1 channels play an important role in the pathogenesis of chronic AV and
      constitute an attractive target for the prevention of arteriopathy. 

PMID- 24312258
TI  - DNA barcode identification of Podocarpaceae--the second largest conifer family.
AB  - We have generated matK, rbcL, and nrITS2 DNA barcodes for 320 specimens
      representing all 18 extant genera of the conifer family Podocarpaceae. The sample
      includes 145 of the 198 recognized species. Comparative analyses of sequence
      quality and species discrimination were conducted on the 159 individuals from
      which all three markers were recovered (representing 15 genera and 97 species).
      The vast majority of sequences were of high quality (B 30 = 0.596-0.989). Even
      the lowest quality sequences exceeded the minimum requirements of the BARCODE
      data standard. In the few instances that low quality sequences were generated,
      the responsible mechanism could not be discerned. There were no statistically
      significant differences in the discriminatory power of markers or marker
      combinations (p = 0.05). The discriminatory power of the barcode markers
      individually and in combination is low (56.7% of species at maximum). In some
      instances, species discrimination failed in spite of ostensibly useful variation
      being present (genotypes were shared among species), but in many cases there was
      simply an absence of sequence variation. Barcode gaps (maximum intraspecific p
      distance > minimum interspecific p-distance) were observed in 50.5% of species
      when all three markers were considered simultaneously. The presence of a barcode
      gap was not predictive of discrimination success (p = 0.02) and there was no
      statistically significant difference in the frequency of barcode gaps among
      markers (p = 0.05). In addition, there was no correlation between number of
      individuals sampled per species and the presence of a barcode gap (p = 0.27).

PMID- 24312259
TI  - Evolutionary dynamics of overlapped genes in Salmonella.
AB  - Presence of overlapping genes (OGs) is a common phenomenon in bacterial genomes.
      Most frequently, overlapping genes share coding regions with as few as one
      nucleotide to as many as thousands of nucleotides. Overlapping genes are often co
      regulated, transcriptionally and translationally. Overlapping genes are also
      subject to the whims of evolution, as the gene overlap is known to be disrupted
      in some species/strains and participating genes are sometimes lost in independent
      lineages. Therefore, a better understanding of evolutionary patterns and rates of
      the disruption of overlapping genes is an important component of genome structure
      and evolution of gene function. In this study, we investigate the fate of
      ancestrally overlapping genes in complete genomes from 15 contemporary strains of
      Salmonella species. We find that the fates of overlapping genes inside and
      outside operons are distinctly different. A larger fraction of overlapping genes
      inside operons conserves their overlap as compared to gene pairs outside of the
      operons (average 0.89 vs. 0.83 per genome). However, when overlapping genes in
      the operons separate, one partner is lost more frequently than in those separated
      genes outside of operons (average 0.02 vs. 0.01 per genome). We also investigate
      the fate of a pan set of overlapping genes at the present and ancestral nodes
      over a phylogenetic tree based on genome sequence data, respectively. We propose
      that co-regulation plays important roles on the fates of genes. Furthermore, a
      vast majority of disruptions occurred prior to the common ancestor of all 15
      Salmonella strains, which enables us to obtain an estimate of disruptions between
      Salmonella and E. coli.

PMID- 24312260
TI  - Physiological responses of Zostera marina and Cymodocea nodosa to light
      limitation stress.
AB  - The effects of light-limitation stress were investigated in natural stands of the
      seagrasses Zostera marina and Cymodocea nodosa in Ria Formosa coastal lagoon,
      southern Portugal. Three levels of light attenuation were imposed for 3 weeks in
      two adjacent meadows (2-3 m depth), each dominated by one species. The response
      of photosynthesis to light was determined with oxygen electrodes. Chlorophylls
      and carotenoids were determined by high-pressure liquid chromatography (HPLC).
      Soluble protein, carbohydrates, malondialdehyde and phenol contents were also
      analysed. Both species showed evident signs of photoacclimation. Their maximum
      photosynthetic rates were significantly reduced with shading. Ratios between
      specific light harvesting carotenoids and the epoxidation state of xanthophyll
      cycle carotenoids revealed significantly higher light harvesting efficiency of C.
      nodosa, a competitive advantage in a low light environment. The contents of both
      soluble sugars and starch were considerably lower in Z. marina plants,
      particularly in the rhizomes, decreasing even further with shading. The different
      carbohydrate energy storage strategies found between the two species clearly
      favour C. nodosa's resilience to light deprivation, a condition enhanced by its
      intrinsic arrangement of the pigment pool. On the other hand, Z. marina revealed
      a lower tolerance to light reduction, mostly due to a less plastic arrangement of
      the pigment pool and lower carbohydrate storage. Our findings indicate that Z.
      marina is close to a light-mediated ecophysiological threshold in Ria Formosa. 

PMID- 24312261
TI  - Differences in brain morphological findings between narcolepsy with and without
      cataplexy.
AB  - OBJECTIVE: Maps of fractional anisotropy (FA) and apparent diffusion coefficient
      (ADC) obtained by diffusion tensor imaging (DTI) can detect microscopic axonal
      changes by estimating the diffusivity of water molecules using magnetic resonance
      imaging (MRI). We applied an MRI voxel-based statistical approach to FA and ADC
      maps to evaluate microstructural abnormalities in the brain in narcolepsy and to
      investigate differences between patients having narcolepsy with and without
      cataplexy. METHODS: Twelve patients with drug-naive narcolepsy with cataplexy
      (NA/CA), 12 with drug-naive narcolepsy without cataplexy (NA w/o CA) and 12 age
      matched healthy normal controls (NC) were enrolled. FA and ADC maps for these 3
      groups were statistically compared by using voxel-based one-way ANOVA. In
      addition, we investigated the correlation between FA and ADC values and clinical
      variables in the patient groups. RESULTS: Compared to the NC group, the NA/CA
      group showed higher ADC values in the left inferior frontal gyrus and left
      amygdala, and a lower ADC value in the left postcentral gyrus. The ADC value in
      the right inferior frontal gyrus and FA value in the right precuneus were higher
      for NA/CA group than for the NA w/o CA group. However, no significant differences
      were observed in FA and ADC values between the NA w/o CA and NC groups in any of
      the areas investigated. In addition, no correlation was found between the
      clinical variables and ADC and FA values of any brain areas in these patient
      groups. CONCLUSIONS: Several microstructural changes were noted in the inferior
      frontal gyrus and amygdala in the NA/CA but not in the NA w/o CA group. These
      findings suggest that these 2 narcolepsy conditions have different pathological
      mechanisms: narcolepsy without cataplexy form appears to be a potentially broader
      condition without any significant brain imaging differences from normal controls.

PMID- 24312262
TI  - Association of cytokine and Toll-like receptor gene polymorphisms with severe
      malaria in three regions of Cameroon.
AB  - P. falciparum malaria is one of the most widespread and deadliest infectious
      diseases in children under five years in endemic areas. The disease has been a
      strong force for evolutionary selection in the human genome, and uncovering the
      critical human genetic factors that confer resistance to the disease would
      provide clues to the molecular basis of protective immunity that would be
      invaluable for vaccine development. We investigated the effect of single
      nucleotide polymorphisms (SNPs) on malaria pathology in a case- control study of
      1862 individuals from two major ethnic groups in three regions with intense
      perennial P. falciparum transmission in Cameroon. Twenty nine polymorphisms in
      cytokine and toll-like receptor (TLR) genes as well as the sickle cell trait
      (HbS) were assayed on the Sequenom iPLEX platform. Our results confirm the known
      protective effect of HbS against severe malaria and also reveal a protective
      effect of SNPs in interleukin-10 (IL10) cerebral malaria and hyperpyrexia.
      Furthermore, IL17RE rs708567 GA and hHbS rs334 AT individuals were associated
      with protection from uncomplicated malaria and anaemia respectively in this
      study. Meanwhile, individuals with the hHbS rs334 TT, IL10 rs3024500 AA, and
      IL17RD rs6780995 GA genotypes were more susceptible to severe malarial anaemia,
      cerebral malaria, and hyperpyrexia respectively. Taken together, our results
      suggest that polymorphisms in some immune response genes may have important
      implications for the susceptibility to severe malaria in Cameroonians. Moreover
      using uncomplicated malaria may allow us to identify novel pathways in the early
      development of the disease. 

PMID- 24312263
TI  - Mammalian target of rapamycin complex 2 (mTORC2) is a critical determinant of
      bladder cancer invasion.
AB  - Bladder cancer is the fourth most common cause of cancer in males in the United
      States. Invasive behavior is a major determinant of prognosis. In this study, we
      identified mammalian target of rapamycin complex 2 (mTORC2) as a central
      regulator of bladder cancer cell migration and invasion. mTORC2 activity was
      assessed by the extent of phosphorylation of Ser473 in AKT and determined to be
      approximately 5-fold higher in specimens of invasive human bladder cancer as
      opposed to non-invasive human bladder cancer. The immortalized malignant bladder
      cell lines, UMUC-3, J82 and T24 demonstrated higher baseline mTORC2 activity
      relative to the benign bladder papilloma-derived cell line RT4 and the normal
      urothelial cell line HU1. The malignant bladder cancer cells also demonstrated
      increased migration in transwell and denudation assays, increased invasion of
      matrigel, and increased capacity to invade human bladder specimens. Gene
      silencing of rictor, a critical component of mTORC2, substantially inhibited
      bladder cancer cell migration and invasion. This was accompanied by a significant
      decrease in Rac1 activation and paxillin phosphorylation. These studies identify
      mTORC2 as a major target for neutralizing bladder cancer invasion. 

PMID- 24312264
TI  - Efficient egress of escaping ants stressed with temperature.
AB  - In the present work we investigate the egress times of a group of Argentine ants
      (Linepithema humile) stressed with different heating speeds. We found that the
      higher the temperature ramp is, the faster ants evacuate showing, in this sense,
      a group-efficient evacuation strategy. It is important to note that even when the
      life of ants was in danger, jamming and clogging was not observed near the exit,
      in accordance with other experiments reported in the literature using citronella
      as aversive stimuli. Because of this clear difference between ants and humans, we
      recommend the use of some other animal models for studying competitive egress
      dynamics as a more accurate approach to understanding competitive egress in human
      systems. 

PMID- 24312265
TI  - Quality along the continuum: a health facility assessment of intrapartum and
      postnatal care in Ghana.
AB  - OBJECTIVE: To evaluate quality of routine and emergency intrapartum and postnatal
      care using a health facility assessment, and to estimate "effective coverage" of
      skilled attendance in Brong Ahafo, Ghana. METHODS: We conducted an assessment of
      all 86 health facilities in seven districts in Brong Ahafo. Using performance of
      key signal functions and the availability of relevant drugs, equipment and
      trained health professionals, we created composite quality categories in four
      dimensions: routine delivery care, emergency obstetric care (EmOC), emergency
      newborn care (EmNC) and non-medical quality. Linking the health facility
      assessment to surveillance data we estimated "effective coverage" of skilled
      attendance as the proportion of births in facilities of high quality. FINDINGS:
      Delivery care was offered in 64/86 facilities; only 3-13% fulfilled our
      requirements for the highest quality category in any dimension. Quality was
      lowest in the emergency care dimensions, with 63% and 58% of facilities
      categorized as "low" or "substandard" for EmOC and EmNC, respectively. This
      implies performing less than four EmOC or three EmNC signal functions, and/or
      employing less than two skilled health professionals, and/or that no health
      professionals were present during our visit. Routine delivery care was "low" or
      "substandard" in 39% of facilities, meaning 25/64 facilities performed less than
      six routine signal functions and/or had less than two skilled health
      professionals and/or less than one midwife. While 68% of births were in health
      facilities, only 18% were in facilities with "high" or "highest" quality in all
      dimensions. CONCLUSION: Our comprehensive facility assessment showed that quality
      of routine and emergency intrapartum and postnatal care was generally low in the
      study region. While coverage with facility delivery was 68%, we estimated
      "effective coverage" of skilled attendance at 18%, thus revealing a large
      "quality gap." Effective coverage could be a meaningful indicator of progress
      towards reducing maternal and newborn mortality.

PMID- 24312266
TI  - Targeting of herpes simplex virus 1 thymidine kinase gene sequences into the OCT4
      locus of human induced pluripotent stem cells.
AB  - The in vitro differentiation of human induced pluripotent stem cells (hiPSC) to
      generate specific types of cells is inefficient, and the remaining
      undifferentiated cells may form teratomas. This raises safety concerns for
      clinical applications of hiPSC-derived cellular products. To improve the safety
      of hiPSC, we attempted to site-specifically insert a herpes simplex virus 1
      thymidine kinase (HSV1-TK) suicide gene at the endogenous OCT4 (POU5F1) locus of
      hiPSC. Since the endogenous OCT4 promoter is active in undifferentiated cells
      only, we speculated that the HSV1-TK suicide gene will be transcribed in
      undifferentiated cells only and that the remaining undifferentiated cells can be
      depleted by treating them with the prodrug ganciclovir (GCV) prior to
      transplantation. To insert the HSV1-TK gene at the OCT4 locus, we cotransfected
      hiPSC with a pair of plasmids encoding an OCT4-specific zinc finger nuclease
      (ZFN) and a donor plasmid harboring a promoter-less transgene cassette consisting
      of HSV1-TK and puromycin resistance gene sequences, flanked by OCT4 gene
      sequences. Puromycin resistant clones were established and characterized
      regarding their sensitivity to GCV and the site of integration of the HSV1
      TK/puromycin resistance gene cassette. Of the nine puromycin-resistant iPSC
      clones analyzed, three contained the HSV1-TK transgene at the OCT4 locus, but
      they were not sensitive to GCV. The other six clones were GCV-sensitive, but the
      TK gene was located at off-target sites. These TK-expressing hiPSC clones
      remained GCV sensitive for up to 90 days, indicating that TK transgene expression
      was stable. Possible reasons for our failed attempt to selectively target the
      OCT4 locus are discussed. 

PMID- 24312267
TI  - B-type natriuretic peptide-induced delayed modulation of TRPV1 and P2X3 receptors
      of mouse trigeminal sensory neurons.
AB  - Important pain transducers of noxious stimuli are small- and medium-diameter
      sensory neurons that express transient receptor vanilloid-1 (TRPV1) channels
      and/or adenosine triphosphate (ATP)-gated P2X3 receptors whose activity is
      upregulated by endogenous neuropeptides in acute and chronic pain models. Little
      is known about the role of endogenous modulators in restraining the expression
      and function of TRPV1 and P2X3 receptors. In dorsal root ganglia, evidence
      supports the involvement of the natriuretic peptide system in the modulation of
      nociceptive transmission especially via the B-type natriuretic peptide (BNP) that
      activates the natriuretic peptide receptor-A (NPR-A) to downregulate sensory
      neuron excitability. Since the role of BNP in trigeminal ganglia (TG) is unclear,
      we investigated the expression of BNP in mouse TG in situ or in primary cultures
      and its effect on P2X3 and TRPV1 receptors of patch-clamped cultured neurons.
      Against scant expression of BNP, almost all neurons expressed NPR-A at membrane
      level. While BNP rapidly increased cGMP production and Akt kinase
      phosphorylation, there was no early change in passive neuronal properties or
      responses to capsaicin, alpha,beta-meATP or GABA. Nonetheless, 24 h application
      of BNP depressed TRPV1 mediated currents (an effect blocked by the NPR-A
      antagonist anantin) without changing responses to alpha,beta-meATP or GABA.
      Anantin alone decreased basal cGMP production and enhanced control alpha,beta
      meATP-evoked responses, implying constitutive regulation of P2X3 receptors by
      ambient BNP. These data suggest a slow modulatory action by BNP on TRPV1 and P2X3
      receptors outlining the role of this peptide as a negative regulator of
      trigeminal sensory neuron excitability to nociceptive stimuli. 

PMID- 24312268
TI  - Relationships among smoking habits, airflow limitations, and metabolic
      abnormalities in school workers.
AB  - BACKGROUND: Chronic obstructive pulmonary disease is caused mainly by habitual
      smoking and is common among elderly individuals. It involves not only airflow
      limitation but also metabolic disorders, leading to increased cardiovascular
      morbidity and mortality. OBJECTIVE: We evaluated relationships among smoking
      habits, airflow limitation, and metabolic abnormalities. METHODS: Between 2001
      and 2008, 15,324 school workers (9700 males, 5624 females; age: >= 30 years)
      underwent medical checkups, including blood tests and spirometry. They also
      responded to a questionnaire on smoking habits and medical history. RESULTS:
      Airflow limitation was more prevalent in current smokers than in ex-smokers and
      never-smokers in men and women. The frequency of hypertriglyceridemia was higher
      in current smokers in all age groups, and those of low high-density-lipoprotein
      cholesterolemia and diabetes mellitus were higher in current smokers in age
      groups >= 40 s in men, but not in women. There were significant differences in
      the frequencies of metabolic abnormalities between subjects with airflow
      limitations and those without in women, but not in men. Smoking index was an
      independent factor associated with increased frequencies of hypertriglyceridemia
      (OR 1.015; 95% CI: 1.012-1.018; p<0.0001) and low high-density-lipoprotein
      cholesterolemia (1.013; 1.010-1.016; p<0.0001) in men. Length of smoking
      cessation was an independent factor associated with a decreased frequency of
      hypertriglyceridemia (0.984; 0.975-0.994; p = 0.007). CONCLUSIONS: Habitual
      smoking causes high incidences of airflow limitation and metabolic abnormalities.
      Women, but not men, with airflow limitation had higher frequencies of metabolic
      abnormalities.

PMID- 24312269
TI  - Snf2 family gene distribution in higher plant genomes reveals DRD1 expansion and
      diversification in the tomato genome.
AB  - As part of large protein complexes, Snf2 family ATPases are responsible for
      energy supply during chromatin remodeling, but the precise mechanism of action of
      many of these proteins is largely unknown. They influence many processes in
      plants, such as the response to environmental stress. This analysis is the first
      comprehensive study of Snf2 family ATPases in plants. We here present a
      comparative analysis of 1159 candidate plant Snf2 genes in 33 complete and
      annotated plant genomes, including two green algae. The number of Snf2 ATPases
      shows considerable variation across plant genomes (17-63 genes). The DRD1,
      Rad5/16 and Snf2 subfamily members occur most often. Detailed analysis of the
      plant-specific DRD1 subfamily in related plant genomes shows the occurrence of a
      complex series of evolutionary events. Notably tomato carries unexpected gene
      expansions of DRD1 gene members. Most of these genes are expressed in tomato,
      although at low levels and with distinct tissue or organ specificity. In
      contrast, the Snf2 subfamily genes tend to be expressed constitutively in tomato.
      The results underpin and extend the Snf2 subfamily classification, which could
      help to determine the various functional roles of Snf2 ATPases and to target
      environmental stress tolerance and yield in future breeding. 

PMID- 24312271
TI  - Hemodynamic impact of absent or reverse end-diastolic flow in the two umbilical
      arteries in growth-restricted fetuses.
AB  - OBJECTIVE: To determine if bilateral absent or reverse end-diastolic (ARED) flow
      in the two umbilical arteries (UAs) at the perivesical (PVC) segment represents a
      more severe degree of hemodynamic compromise than unilateral ARED flow at the PVC
      segment in singleton pregnancies complicated by intrauterine growth restriction
      (IUGR). METHODS: This was a prospective observational study. One hundred nine
      fetuses with IUGR underwent a total of 225 ultrasound (US) examinations. We
      measured the pulsatility index (PI) from the two UAs at the PVC segment, UA in
      the free floating cord (FFC), middle cerebral artery (MCA), ductus venosus (DV)
      and the aortic isthmus blood flow index (IFI). Three groups were classified
      according to bilateral positive end-diastolic (PED) flow, unilateral ARED flow or
      bilateral ARED flow in the UAs at the PVC segment. RESULTS: The proportions of US
      examinations with PED flow, unilateral ARED flow and bilateral ARED flow in the
      UAs were 54.7%, 20.4%, and 24.9%, respectively. At the last US examination, the
      IFI z-scores were significantly lower in the bilateral ARED group (-6.28 +/-
      4.30) compared to the unilateral ARED group (-1.72 +/- 3.18, p<0.05) and the
      bilateral PED group (-0.83 +/- 2.36, p<0.05), the DV-PI z-scores were
      significantly higher in the bilateral ARED group (2.15 +/- 3.79) compared to the
      bilateral PED group (0.64 +/- 1.50, p<0.05). Before 32 weeks of gestation, the
      interval between US examination and delivery was significantly shorter in the
      bilateral ARED group (8.9 days +/- 8.2) than the unilateral ARED group (15.9 days
      +/- 13.4, p<0.05) and the bilateral PED group (30.3 days +/- 25.7, p<0.05).
      CONCLUSION: There are significant differences in fetal blood fluxes between left
      and right UA. Doppler examination at the PVC segment significantly improves the
      comparability of UA-PI between two successive US examinations and allows a
      longitudinal and independent hemodynamic investigation of each UA. Examination of
      a single UA in free floating cord may miss a large fraction of unilateral ARED
      flow. In singleton IUGR fetuses, a bilateral ARED flow in the UAs at the PVC
      segment indicates more severe hemodynamic compromise and worse fetal conditions
      than unilateral ARED flow.

PMID- 24312270
TI  - Epitopes of microbial and human heat shock protein 60 and their recognition in
      myalgic encephalomyelitis.
AB  - Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common
      disease with chronic fatigability, cognitive dysfunction and myalgia of unknown
      etiology, often starts with an infection. The chaperonin human heat shock protein
      60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic
      and a major autoantigen. The anti-HSP60 humoral (IgG and IgM) immune response was
      studied in 69 ME patients and 76 blood donors (BD) (the Training set) with
      recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted
      peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a
      multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like
      activity, but these and other HSP60 peptides also bound IgG and IgM with an ME
      preference, theoretically indicating a competition between HSP60 function and
      antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated
      with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48
      Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60
      detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff
      (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60
      occurs in a subset of ME, compatible with infection-induced autoimmunity. 

PMID- 24312272
TI  - Inappropriateness of cardiovascular radiological imaging testing; a tertiary care
      referral center study.
AB  - AIMS: Radiological inappropriateness in medical imaging leads to loss of
      resources and accumulation of avoidable population cancer risk. Aim of the study
      was to audit the appropriateness rate of different cardiac radiological
      examinations. METHODS AND PRINCIPAL FINDINGS: With a retrospective, observational
      study we reviewed clinical records of 818 consecutive patients (67 +/- 12 years,
      75% males) admitted from January 1-May 31, 2010 to the National Research Council 
      Tuscany Region Gabriele Monasterio Foundation cardiology division. A total of
      940 procedures were audited: 250 chest x-rays (CXR); 240 coronary computed
      tomographies (CCT); 250 coronary angiographies (CA); 200 percutaneous coronary
      interventions (PCI). For each test, indications were rated on the basis of
      guidelines class of recommendation and level of evidence: definitely appropriate
      (A, including class I, appropriate, and class IIa, probably appropriate),
      uncertain (U, class IIb, probably inappropriate), or inappropriate (I, class III,
      definitely inappropriate). Appropriateness was suboptimal for all tests: CXR (A =
      48%, U = 10%, I = 42%); CCT (A = 58%, U = 24%, I = 18%); CA (A = 45%, U = 25%, I
      = 30%); PCI (A = 63%, U = 15%, I = 22%). Top reasons for inappropriateness were:
      routine on hospital admission (70% of inappropriate CXR); first line application
      in asymptomatic low-risk patients (42% of CCT) or in patients with unchanged
      clinical status post-revascularization (20% of CA); PCI in patients either
      asymptomatic or with miscellaneous symptoms and without inducible ischemia on non
      invasive testing (36% of inappropriate PCI). CONCLUSION AND SIGNIFICANCE: Public
      healthcare system--with universal access paid for with public money--is
      haemorrhaging significant resources and accumulating avoidable long-term cancer
      risk with inappropriate cardiovascular imaging prevention.

PMID- 24312273
TI  - New insights into histidine triad proteins: solution structure of a Streptococcus
      pneumoniae PhtD domain and zinc transfer to AdcAII.
AB  - Zinc (Zn(2+)) homeostasis is critical for pathogen host colonization and
      invasion. Polyhistidine triad (Pht) proteins, located at the surface of various
      streptococci, have been proposed to be involved in Zn(2+) homeostasis. The phtD
      gene, coding for a Zn(2+)-binding protein, is organized in an operon with adcAII
      coding for the extracellular part of a Zn(2+) transporter. In the present work,
      we investigate the relationship between PhtD and AdcAII using biochemical and
      structural biology approaches. Immuno-precipitation experiments on purified
      membranes of Streptococcus pneumoniae (S. pneumoniae) demonstrate that native
      PhtD and AdcAII interact in vivo confirming our previous in vitro observations.
      NMR was used to demonstrate Zn(2+) transfer from the Zn(2+)-bound form of a 137
      amino acid N-terminal domain of PhtD (t-PhtD) to AdcAII. The high resolution NMR
      structure of t-PhtD shows that Zn(2+) is bound in a tetrahedral site by
      histidines 83, 86, and 88 as well as by glutamate 63. Comparison of the NMR
      parameters measured for apo- and Zn(2+)-t-PhtD shows that the loss of Zn(2+)
      leads to a diminished helical propensity at the C-terminus and increases the
      local dynamics and overall molecular volume. Structural comparison with the
      crystal structure of a 55-long fragment of PhtA suggests that Pht proteins are
      built from short repetitive units formed by three beta-strands containing the
      conserved HxxHxH motif. Taken together, these results support a role for S.
      pneumoniae PhtD as a Zn(2+) scavenger for later release to the surface
      transporter AdcAII, leading to Zn(2+) uptake. 

PMID- 24312274
TI  - ALS-associated TDP-43 induces endoplasmic reticulum stress, which drives
      cytoplasmic TDP-43 accumulation and stress granule formation.
AB  - In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR
      DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons
      and glia, where it associates with stress granules (SGs) and forms large
      inclusions. SGs form in response to cellular stress, including endoplasmic
      reticulum (ER) stress, which is induced in both familial and sporadic forms of
      ALS. Here we demonstrate that pharmacological induction of ER stress causes TDP
      43 to accumulate in the cytoplasm, where TDP-43 also associates with SGs.
      Furthermore, treatment with salubrinal, an inhibitor of dephosphorylation of
      eukaryotic initiation factor 2-alpha, a key modulator of ER stress, potentiates
      ER stress-mediated SG formation. Inclusions of C-terminal fragment TDP-43,
      reminiscent of disease-pathology, form in close association with ER and Golgi
      compartments, further indicating the involvement of ER dysfunction in TDP-43
      associated disease. Consistent with this notion, over-expression of ALS-linked
      mutant TDP-43, and to a lesser extent wildtype TDP-43, triggers several ER stress
      pathways in neuroblastoma cells. Similarly, we found an interaction between the
      ER chaperone protein disulphide isomerase and TDP-43 in transfected cell lysates
      and in the spinal cords of mutant A315T TDP-43 transgenic mice. This study
      provides evidence for ER stress as a pathogenic pathway in TDP-43-mediated
      disease. 

PMID- 24312275
TI  - Natural stilbenoids isolated from grapevine exhibiting inhibitory effects against
      HIV-1 integrase and eukaryote MOS1 transposase in vitro activities.
AB  - Polynucleotidyl transferases are enzymes involved in several DNA mobility
      mechanisms in prokaryotes and eukaryotes. Some of them such as retroviral
      integrases are crucial for pathogenous processes and are therefore good
      candidates for therapeutic approaches. To identify new therapeutic compounds and
      new tools for investigating the common functional features of these proteins, we
      addressed the inhibition properties of natural stilbenoids deriving from
      resveratrol on two models: the HIV-1 integrase and the eukaryote MOS-1
      transposase. Two resveratrol dimers, leachianol F and G, were isolated for the
      first time in Vitis along with fourteen known stilbenoids: E-resveratrol, E
      piceid, E-pterostilbene, E-piceatannol, (+)-E-epsilon-viniferin, E-epsilon
      viniferinglucoside, E-scirpusin A, quadragularin A, ampelopsin A, pallidol, E
      miyabenol C, E-vitisin B, hopeaphenol, and isohopeaphenol and were purified from
      stalks of Vitis vinifera (Vitaceae), and moracin M from stem bark of
      Milliciaexelsa (Moraceae). These compounds were tested in in vitro and in vivo
      assays reproducing the activity of both enzymes. Several molecules presented
      significant inhibition on both systems. Some of the molecules were found to be
      active against both proteins while others were specific for one of the two
      models. Comparison of the differential effects of the molecules suggested that
      the compounds could target specific intermediate nucleocomplexes of the
      reactions. Additionally E-pterostilbene was found active on the early lentiviral
      replication steps in lentiviruses transduced cells. Consequently, in addition to
      representing new original lead compounds for further modelling of new active
      agents against HIV-1 integrase, these molecules could be good tools for
      identifying such reaction intermediates in DNA mobility processes. 

PMID- 24312276
TI  - Down-regulation of miR-126 is associated with colorectal cancer cells
      proliferation, migration and invasion by targeting IRS-1 via the AKT and ERK1/2
      signaling pathways.
AB  - BACKGROUND: Colorectal carcinoma (CRC) is one of the leading causes of cancer
      related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in
      carcinogenesis. MiR-126 has been shown to be down-regulated in CRC. In this
      study, we identified the potential effects of miR-126 on some important
      biological properties of CRC cells and clarified the regulation of insulin
      receptor substrate 1 (IRS-1) and its possible signaling pathway by miR-126.
      METHODS: The effect of miR-126 on IRS-1, AKT, and ERK1/2 expression was assessed
      in the CRC cell lines HT-29 and HCT-116 with a miR-126 mimic or inhibitor to
      increase or decrease miR-126 expression. Furthermore, the roles of miR-126 in
      regulation of the biological properties of CRC cells were analyzed with miR-126
      mimic or inhibitor-transfected cells. The 3'-untranslated region (3'-UTR) of IRS
      1 regulated by miR-126 was analyzed by using a dual-luciferase reporter assay.
      RESULTS: We found that IRS-1 is the functional downstream target of miR-126 by
      directly targeting the 3'-UTR of IRS-1. Endogenous miR-126 and exogenous miR-126
      mimic inhibited IRS-1 expression. Furthermore, gain-of-function or loss-of
      function studies showed that over-expression of miR-126 down-regulated IRS-1,
      suppressed AKT and ERK1/2 activation, CRC cells proliferation, migration,
      invasion, and caused cell cycle arrest, but had no effect on cell apoptosis.
      Knockdown of miR-126 promoted these processes in HCT-116 cells and promoted AKT
      and ERK1/2 activation by up-regulating the expression of the IRS-1 protein.
      CONCLUSIONS: MiR-126 may play roles in regulation of the biological behavior of
      CRC cells, at least in part, by targeting IRS-1 via AKT and ERK1/2 signaling
      pathways.

PMID- 24312277
TI  - Association of pol diversity with antiretroviral treatment outcomes among HIV
      infected African children.
AB  - BACKGROUND: In HIV-infected children, viral diversity tends to increase with age
      in the absence of antiretroviral treatment (ART). We measured HIV diversity in
      African children (ages 6-36 months) enrolled in a randomized clinical trial
      comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort
      were exposed to single dose nevirapine (sdNVP) at birth. METHODS: HIV diversity
      was measured retrospectively using a high resolution melting (HRM) diversity
      assay. Samples were obtained from 139 children at the enrollment visit prior to
      ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in
      pol, and three in env. A single numeric HRM score that reflects HIV diversity was
      generated for each region; composite HRM scores were also calculated (mean and
      median for all six regions). RESULTS: In multivariable median regression models
      using backwards selection that started with demographic and clinical variables,
      older age was associated with higher HRM scores (higher HIV diversity) in pol (P
      = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In
      multivariable models adjusted for age, pre-treatment HIV viral load, pre
      treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were
      associated with shorter time to virologic suppression (P = 0.016) and longer time
      to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment;
      P<0.001 for all measures). CONCLUSIONS: In this cohort of sdNVP-exposed, ART
      naive African children, higher levels of HIV diversity in the HIV pol region
      prior to ART initiation were associated with better treatment outcomes.

PMID- 24312279
TI  - Ribosomal internal transcribed spacer of Prototheca wickerhamii has
      characteristic structure useful for identification and genotyping.
AB  - Prototheca species are achlorophyllous algae ubiquitous in nature and known to
      cause localized and systemic infection both in humans and animals. Although
      identification of the Prototheca species in clinical specimens is a challenge,
      there are an increasing number of cases in which molecular techniques have
      successfully been used for diagnosis of protothecosis. In this study, we
      characterized nuclear ribosomal DNA (rDNA) of a strain of Prototheca (FL11-0001)
      isolated from a dermatitis patient in Japan for its species identification. When
      nuclear rDNA of FL11-0001 and that of various other Prototheca strains were
      compared by polymerase chain reaction (PCR), the results indicated that the sizes
      of ribosomal internal transcribed spacer (ITS) were different in a species
      dependent manner, suggesting that the variation might be useful for
      differentiation of Prototheca spp. Especially, ITS of P. wickerhamii, the most
      common cause of human protothecosis, was distinctively larger than that of other
      Prototheca spp. FL11-0001, whose ITS was comparably large, could easily be
      identified as P. wickerhamii. The usefulness of the PCR analysis of ITS was also
      demonstrated by the discovery that one of the clinical isolates that had
      previously been designated as P. wickerhamii was likely a novel species.
      Furthermore, our data demonstrated that nucleotide sequences of P. wickerhamii
      ITS are heterogenous between different rDNA copies in each strain and also
      polymorphic between strains. Phylogenetic analysis suggested that the ITS
      sequences could be classified to four clades, based on which P. wickerhamii
      strains might be grouped into at least two genotypes. Comprehensive
      characterization of Prototheca rDNA may provide valuable insights into diagnosis
      and epidemiology of protothecosis, as well as evolution and taxonomy of
      Prototheca and related organisms. 

PMID- 24312278
TI  - TOX4 and NOVA1 proteins are partners of the LEDGF PWWP domain and affect HIV-1
      replication.
AB  - PWWP domains are involved in the chromatin attachment of several proteins. They
      bind to both DNA and proteins and their interaction with specific histone
      methylation marks define them as a new class of histone code readers. The lens
      epithelium derived growth factor (LEDGF/p75) contains an N-terminal PWWP domain
      necessary for its interaction with chromatin but also a C-terminal domain which
      interacts with several proteins, such as lentiviral integrases. These two domains
      confer a chromatin-tethering function to LEDGF/p75 and in the case of lentiviral
      integrases, this tethering participates in the efficiency and site selectivity of
      integration. Although proteins interacting with LEDGF/p75 C-terminal domain have
      been extensively studied, no data exist about partners of its PWWP domain
      regulating its interaction with chromatin. In this study, we report the
      identification by yeast-two-hybrid of thirteen potential partners of the LEDGF
      PWWP domain. Five of these interactions were confirmed in mammalian cells, using
      both a protein complementation assay and co-immunoprecipitation approaches. Three
      of these partners interact with full length LEDGF/p75, they are specific for PWWP
      domains of the HDGF family and they require PWWP amino acids essential for the
      interaction with chromatin. Among them, the transcription activator TOX4 and the
      splicing cofactor NOVA1 were selected for a more extensive study. These two
      proteins or their PWWP interacting regions (PIR) colocalize with LEDGF/p75 in
      Hela cells and interact in vitro in the presence of DNA. Finally, single round
      VSV-G pseudotyped HIV-1 but not MLV infection is inhibited in cells
      overexpressing these two PIRs. The observed inhibition of infection can be
      attributed to a defect in the integration step. Our data suggest that a
      regulation of LEDGF interaction with chromatin by cellular partners of its PWWP
      domain could be involved in several processes linked to LEDGF tethering
      properties, such as lentiviral integration, DNA repair or transcriptional
      regulation. 

PMID- 24312280
TI  - Analysis of the distribution of magnetic fluid inside tumors by a giant
      magnetoresistance probe.
AB  - Magnetic fluid hyperthermia (MFH) therapy uses the magnetic component of
      electromagnetic fields in the radiofrequency spectrum to couple energy to
      magnetic nanoparticles inside tumors. In MFH therapy, magnetic fluid is injected
      into tumors and an alternating current (AC) magnetic flux is applied to heat the
      magnetic fluid- filled tumor. If the temperature can be maintained at the
      therapeutic threshold of 42  degrees C for 30 minutes or more, the tumor cells
      can be destroyed. Analyzing the distribution of the magnetic fluid injected into
      tumors prior to the heating step in MFH therapy is an essential criterion for
      homogenous heating of tumors, since a decision can then be taken on the strength
      and localization of the applied external AC magnetic flux density needed to
      destroy the tumor without affecting healthy cells. This paper proposes a
      methodology for analyzing the distribution of magnetic fluid in a tumor by a
      specifically designed giant magnetoresistance (GMR) probe prior to MFH heat
      treatment. Experimental results analyzing the distribution of magnetic fluid
      suggest that different magnetic fluid weight densities could be estimated inside
      a single tumor by the GMR probe.

PMID- 24312281
TI  - Plant-pollinator coextinctions and the loss of plant functional and phylogenetic
      diversity.
AB  - Plant-pollinator coextinctions are likely to become more frequent as habitat
      alteration and climate change continue to threaten pollinators. The consequences
      of the resulting collapse of plant communities will depend partly on how quickly
      plant functional and phylogenetic diversity decline following pollinator
      extinctions. We investigated the functional and phylogenetic consequences of
      pollinator extinctions by simulating coextinctions in seven plant-pollinator
      networks coupled with independent data on plant phylogeny and functional traits.
      Declines in plant functional diversity were slower than expected under a scenario
      of random extinctions, while phylogenetic diversity often decreased faster than
      expected by chance. Our results show that plant functional diversity was
      relatively robust to plant-pollinator coextinctions, despite the underlying rapid
      loss of evolutionary history. Thus, our study suggests the possibility of
      uncoupled responses of functional and phylogenetic diversity to species
      coextinctions, highlighting the importance of considering both dimensions of
      biodiversity explicitly in ecological studies and when planning for the
      conservation of species and interactions. 

PMID- 24312282
TI  - Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's
      disease: quantitative autoradiography in postmortem human brain.
AB  - Early Alzheimer's disease (AD) is characterized by memory loss and hippocampal
      atrophy with relative sparing of basal ganglia. Activation of glutamate NMDA
      receptors in the hippocampus is an important step in memory formation. We
      measured the density of NMDA receptors in samples of hippocampus, entorhinal
      cortex and basal ganglia obtained from subjects who died with pathologically
      confirmed AD and age- and sex- matched non-demented controls. We found
      significant decreases in NMDA receptor density in the hippocampus and entorhinal
      cortex but not in the basal ganglia. Loss of NMDA receptors was significantly
      correlated with neuropathological progression as assessed by Braak staging
      postmortem. The same samples were probed for neuroinflammation by measuring the
      density and gene expression of translocator protein 18 kDA (TSPO), an established
      marker of microglial activation. Unlike NMDA receptor loss, increased densities
      of TSPO were found in all of the brain regions sampled. However hippocampal, but
      not striatal TSPO density and gene expression were inversely correlated with NMDA
      receptor density and positively correlated with Braak stage, suggesting NMDA
      receptors exacerbate neuroniflammatory damage. The high correlation between
      hippocampal NMDA receptor loss and disease progression supports the use of non
      invasive imaging with NMDA receptor tracers and positron emission tomography as a
      superior method for diagnosis, staging and treatment monitoring of AD in vivo.

PMID- 24312283
TI  - Automated cell tracking and analysis in phase-contrast videos (iTrack4U):
      development of Java software based on combined mean-shift processes.
AB  - Cell migration is a key biological process with a role in both physiological and
      pathological conditions. Locomotion of cells during embryonic development is
      essential for their correct positioning in the organism; immune cells have to
      migrate and circulate in response to injury. Failure of cells to migrate or an
      inappropriate acquisition of migratory capacities can result in severe defects
      such as altered pigmentation, skull and limb abnormalities during development,
      and defective wound repair, immunosuppression or tumor dissemination. The ability
      to accurately analyze and quantify cell migration is important for our
      understanding of development, homeostasis and disease. In vitro cell tracking
      experiments, using primary or established cell cultures, are often used to study
      migration as cells can quickly and easily be genetically or chemically
      manipulated. Images of the cells are acquired at regular time intervals over
      several hours using microscopes equipped with CCD camera. The locations (x,y,t)
      of each cell on the recorded sequence of frames then need to be tracked. Manual
      computer-assisted tracking is the traditional method for analyzing the migratory
      behavior of cells. However, this processing is extremely tedious and time
      consuming. Most existing tracking algorithms require experience in programming
      languages that are unfamiliar to most biologists. We therefore developed an
      automated cell tracking program, written in Java, which uses a mean-shift
      algorithm and ImageJ as a library. iTrack4U is a user-friendly software. Compared
      to manual tracking, it saves considerable amount of time to generate and analyze
      the variables characterizing cell migration, since they are automatically
      computed with iTrack4U. Another major interest of iTrack4U is the standardization
      and the lack of inter-experimenter differences. Finally, iTrack4U is adapted for
      phase contrast and fluorescent cells. 

PMID- 24312284
TI  - Reliability and validity of the multimedia activity recall in children and adults
      (MARCA) in people with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the reliability and validity of the Multimedia Activity
      Recall for Children and Adults (MARCA) in people with chronic obstructive
      pulmonary disease (COPD). DESIGN: People with COPD and their carers completed the
      Multimedia Activity Recall for Children and Adults (MARCA) for four, 24-hour
      periods (including test-retest of 2 days) while wearing a triaxial accelerometer
      (Actigraph GT3X+(r)), a multi-sensor armband (Sensewear Pro3(r)) and a pedometer
      (New Lifestyles 1000(r)). SETTING: Self reported activity recalls (MARCA) and
      objective activity monitoring (Accelerometry) were recorded under free-living
      conditions. PARTICIPANTS: 24 couples were included in the analysis (COPD; age
      74.4 +/- 7.9 yrs, FEV1 54 +/- 13% Carer; age 69.6 +/- 10.9 yrs, FEV1 99 +/- 24%).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Test-retest reliability was
      compared for MARCA activity domains and different energy expenditure zones.
      Validity was assessed between MARCA-derived physical activity level (in metabolic
      equivalent of task (MET) per minute), duration of moderate to vigorous physical
      activity (min) and related data from the objective measurement devices. Analysis
      included intra-class correlation coefficients (ICC), Bland-Altman analyses,
      paired t-tests (p) and Spearman's rank correlation coefficients (rs). RESULTS:
      Reliability between occasions of recall for all activity domains was uniformly
      high, with test-retest correlations consistently >0.9. Validity correlations were
      moderate to strong (rs = 0.43-0.80) across all comparisons. The MARCA yields
      comparable PAL estimates and slightly higher moderate to vigorous physical
      activity (MVPA) estimates. CONCLUSION: In older adults with chronic illness, the
      MARCA is a valid and reliable tool for capturing not only the time and energy
      expenditure associated with physical and sedentary activities but also
      information on the types of activities.

PMID- 24312285
TI  - Strategies for expanding the operational range of channelrhodopsin in optogenetic
      vision.
AB  - Some hereditary diseases, such as retinitis pigmentosa, lead to blindness due to
      the death of photoreceptors, though the rest of the visual system might be only
      slightly affected. Optogenetics is a promising tool for restoring vision after
      retinal degeneration. In optogenetics, light-sensitive ion channels
      ("channelrhodopsins") are expressed in neurons so that the neurons can be
      activated by light. Currently existing variants of channelrhodopsin--engineered
      for use in neurophysiological research--do not necessarily support the goal of
      vision restoration optimally, due to two factors: First, the nature of the light
      stimulus is fundamentally different in "optogenetic vision" compared to
      "optogenetic neuroscience". Second, the retinal target neurons have specific
      properties that need to be accounted for, e.g. most retinal neurons are non
      spiking. In this study, by using a computational model, we investigate properties
      of channelrhodopsin that might improve successful vision restoration. We pay
      particular attention to the operational brightness range and suggest strategies
      that would allow optogenetic vision over a wider intensity range than currently
      possible, spanning the brightest 5 orders of naturally occurring luminance. We
      also discuss the biophysical limitations of channelrhodopsin, and of the
      expressing cells, that prevent further expansion of this operational range, and
      we suggest design strategies for optogenetic tools which might help overcoming
      these limitations. Furthermore, the computational model used for this study is
      provided as an interactive tool for the research community.

PMID- 24312286
TI  - A missense mutation in CRYBB2 leads to progressive congenital membranous cataract
      by impacting the solubility and function of betaB2-crystallin.
AB  - Congenital cataract is a major cause of visual impairment and childhood
      blindness. The solubility and stability of crystallin proteins play critical
      roles in maintaining the optical transparency of the lens during the life span.
      Previous studies have shown that approximately 8.3%~25% of congenital cataracts
      are inherited, and mutations in crystallins are the most common. In this study,
      we attempted to identify the genetic defect in a four-generation family affected
      with congenital cataracts. The congenital cataract phenotype of this four
      generation family was identified as membranous cataract by slit-lamp photography.
      Mutation screening of the candidate genes detected a heterozygous c.465G -> C
      change in the exon6 of the betaB2-crystallin gene (CRYBB2) in all family members
      affected with cataracts, resulting in the substitution of a highly conserved
      Tryptophan to Cystine (p.W151C). The mutation was confirmed by restriction
      fragment length polymorphism (RFLP) analysis and found that the transition
      resulted in the absence of a BslI restriction site in the affected members of the
      pedigree. The outcome of PolyPhen-2 and SIFT analysis predicted that this W151C
      mutation would probably damage to the structure and function of betaB2
      crystallin. Wild type (wt) and W151C mutant betaB2-crystallin were expressed in
      human lens epithelial cells (HLECs), and the fluorescence results showed that Wt
      betaB2-crystallin was evenly distributed throughout the cells, whereas
      approximately 34.7% of cells transfected with the W151C mutant betaB2-crystallin
      formed intracellular aggregates. Taken together, these data suggest that the
      missense mutation in CRYBB2 gene leads to progressive congenital membranous
      cataract by impacting the solubility and function of betaB2-crystallin.

PMID- 24312287
TI  - Fluorescent protein voltage probes derived from ArcLight that respond to membrane
      voltage changes with fast kinetics.
AB  - We previously reported the discovery of a fluorescent protein voltage probe,
      ArcLight, and its derivatives that exhibit large changes in fluorescence
      intensity in response to changes of plasma membrane voltage. ArcLight allows the
      reliable detection of single action potentials and sub-threshold activities in
      individual neurons and dendrites. The response kinetics of ArcLight (tau1-on ~10
      ms, tau2-on ~ 50 ms) are comparable with most published genetically-encoded
      voltage probes. However, probes using voltage-sensing domains other than that
      from the Ciona intestinalis voltage sensitive phosphatase exhibit faster
      kinetics. Here we report new versions of ArcLight, in which the Ciona voltage
      sensing domain was replaced with those from chicken, zebrafish, frog, mouse or
      human. We found that the chicken and zebrafish-based ArcLight exhibit faster
      kinetics, with a time constant (tau) less than 6 ms for a 100 mV depolarization.
      Although the response amplitude of these two probes (8-9%) is not as large as the
      Ciona-based ArcLight (~35%), they are better at reporting action potentials from
      cultured neurons at higher frequency. In contrast, probes based on frog, mouse
      and human voltage sensing domains were either slower than the Ciona-based
      ArcLight or had very small signals.

PMID- 24312288
TI  - A cell permeable peptide targeting the intracellular loop 2 of endothelin B
      receptor reduces pulmonary hypertension in a hypoxic rat model.
AB  - Cell permeable peptides (CPP) aid cellular uptake of targeted cargo across the
      hydrophobic plasma membrane. CPP-mediated cargo delivery of receptor signaling
      motifs provides an opportunity to regulate specific receptor initiated signaling
      cascades. Both endothelin-1 receptors, ETA and ETB, have been targets of
      antagonist therapies for individuals with pulmonary arterial hypertension (PAH).
      These therapies have had success but have been accompanied by adverse reactions.
      Also, unlike the CPP which target specific signaling cascades, the antagonists
      target the entire function of the receptor. Using the CPP strategy of biased
      antagonism of the ETB receptor's intracellular loop 2 (ICB2), we demonstrate
      blunting of hypoxic pulmonary hypertension (HPH) in the rat, including indices of
      pulmonary arterial pressure, right ventricular hypertrophy and pulmonary vascular
      remodeling. Further, ex vivo analysis of the pulmonary artery treated with the
      IC2B peptide upon injection manifests marked reductions in Akt and ERK
      activation. Both kinases have been intimately related to cell proliferation and
      vascular contraction, the hallmarks of PAH. These observations in sum illustrate
      an involvement of the ETB receptor in HPH and furthermore provide a basis for a
      novel, CPP-based, strategy in the treatment of PAH, ultimately able to target not
      only ET-1, but also other factors involved in the development of PAH. 

PMID- 24312289
TI  - Paradoxical regulation of hypoxia inducible factor-1alpha (HIF-1alpha) by histone
      deacetylase inhibitor in diffuse large B-cell lymphoma.
AB  - Hypoxia inducible factor (HIF) is important in cancer, as it regulates various
      oncogenic genes as well as genes involved in cell survival, proliferation, and
      migration. Elevated HIF-1 protein promotes a more aggressive tumor phenotype, and
      greater HIF-1 expression has been demonstrated to correlate with poorer
      prognosis, increased risk of metastasis and increased mortality. Recent reports
      suggest that HIF-1 activates autophagy, a lysosomal degradation pathway which may
      promote tumor cell survival. We show here that HIF-1alpha expression is
      constitutively active in multiple diffuse large B cell lymphoma (DLBCL) cell
      lines under normoxia and it is regulated by the PI3K/AKT pathway. PCI-24781, a
      pan histone deacetylase inhibitor (HDACI), enhanced accumulation of HIF-1alpha
      and induced autophagy initially, while extended incubation with the drug resulted
      in inhibition of HIF-1alpha. We tested the hypothesis that PCI-24781- induced
      autophagy is mediated by HIF-1alpha and that inhibition of HIF-1alpha in these
      cells results in attenuation of autophagy and decreased survival. We also provide
      evidence that autophagy serves as a survival pathway in DLBCL cells treated with
      PCI-24781 which suggests that the use of autophagy inhibitors such as chloroquine
      or 3-methyl adenine in combination with PCI-24781 may enhance apoptosis in
      lymphoma cells. 

PMID- 24312290
TI  - Blood amyloid beta levels in healthy, mild cognitive impairment and Alzheimer's
      disease individuals: replication of diastolic blood pressure correlations and
      analysis of critical covariates.
AB  - Plasma amyloid beta (Abeta) levels are being investigated as potential biomarkers
      for Alzheimer's disease. In AB128 cross-sectional study, a number of medical
      relevant correlates of blood Abeta40 or Abeta42 were analyzed in 140 subjects (51
      Alzheimer's disease patients, 53 healthy controls and 36 individuals diagnosed
      with mild cognitive impairment). We determined the association between multiple
      variables with Abeta40 and Abeta42 levels measured in three different blood
      compartments called i) Abeta directly accessible (DA) in the plasma, ii) Abeta
      recovered from the plasma matrix (RP) after diluting the plasma sample in a
      formulated buffer, and iii) associated with the remaining cellular pellet (CP).
      We confirmed that diastolic blood pressure (DBP) is consistently correlated with
      blood DA Abeta40 levels (r=-0.19, P=0.032). These results were consistent in the
      three phenotypic groups studied. Importantly, the observation resisted
      covariation with age, gender or creatinine levels. Observed effect size and
      direction of Abeta40 levels/DBP correlation are in accordance with previous
      reports. Of note, DA Abeta40 and the RP Abeta40 were also strongly associated
      with creatinine levels (r=0.599, P<<0.001) and to a lesser extent to urea, age,
      hematocrit, uric acid and homocysteine (p<0.001). DBP and the rest of statistical
      significant correlates identified should be considered as potential confounder
      factors in studies investigating blood Abeta levels as potential AD biomarker.
      Remarkably, the factors affecting Abeta levels in plasma (DA, RP) and blood cell
      compartments (CP) seem completely different. 

PMID- 24312291
TI  - Down-regulation of Gab1 inhibits cell proliferation and migration in hilar
      cholangiocarcinoma.
AB  - Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the
      hilar biliary duct epithelium. Due to few effective comprehensive treatments, the
      prognosis of hilar cholangiocarcinoma is poor. In this study,
      immunohistochemistry was first used to detect and analyze the expression of Gab1,
      VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships
      to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were
      used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect
      the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors
      of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly
      expressed and positively correlated with each other in hilar cholangiocarcinoma
      tissues, which were related to lymph node metastasis and differentiation. 2.
      After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9
      levels were decreased in ICBD-1 cells. At the same time, cell proliferation
      decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion
      decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9
      are significantly related to the malignant biological behavior of hilar
      cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the
      VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and
      influences the invasion of tumor cells via MMP-9. 

PMID- 24312292
TI  - Which urban migrants default from tuberculosis treatment in Shanghai, China?
AB  - BACKGROUND: Migration is a major challenge to tuberculosis (TB) control
      worldwide. TB treatment requires multiple drugs for at least six months. Some TB
      patients default before completing their treatment regimen, which can lead to
      ongoing infectiousness and drug resistance. METHODS: We conducted a retrospective
      analysis of 29,943 active TB cases among urban migrants that were reported
      between 2000 to 2008 in Shanghai, China. We used logistic regression models to
      identify factors independently associated with treatment defaults in TB patients
      among urban migrants during 2005-2008. RESULTS: Fifty-two percent of the total TB
      patients reported in Shanghai during the study period were among urban migrants.
      Three factors increased the odds of a treatment default: case management using
      self-administered therapy (OR, 5.84, 95% CI, 3.14-10.86, p<0.0005), being a
      retreatment case (OR, 1.47, 95% CI, 1.25-1.71, p<0.0005), and age >60 years old
      (OR, 1.33, 95% CI, 1.05-1.67, p=0.017). The presence of a cavity in the initial
      chest radiograph decreased the odds for a treatment default (OR, 0.87, 95% CI,
      0.77-0.97, p=0.015), as did migration from central China (OR, 0.85, 95% CI, 0.73
      0.99, p=0.042), case management by family members (OR, 0.73, 95% CI 0.66-0.81,
      p<0.0005), and the combination of case detection by a required physical exam and
      case management by health care staff (OR, 0.64, 95% CI, 0.45-0.93, p=0.019).
      CONCLUSION: Among TB patients who were urban migrants in Shanghai, case
      management using self-administered therapy was the strongest modifiable risk
      factor that was independently associated with treatment defaults. Interventions
      that target retreated TB cases could also reduce treatment defaults among urban
      migrants. Health departments should develop effective measures to prevent
      treatment defaults among urban migrants, to ensure completion of therapy among
      urban migrants who move between cities and provinces, and to improve reporting of
      treatment outcomes.

PMID- 24312293
TI  - Reduced face aftereffects in autism are not due to poor attention.
AB  - This study aimed to determine why face identity aftereffects are diminished in
      children with autism, relative to typical children. To address the possibility
      that reduced face aftereffects might reflect reduced attention to adapting
      stimuli, we investigated the consequence of controlling attention to adapting
      faces during a face identity aftereffect task in children with autism and typical
      children. We also included a size-change between adaptation and test stimuli to
      determine whether the reduced aftereffects reflect atypical adaptation to low- or
      higher-level stimulus properties. Results indicated that when attention was
      controlled and directed towards adapting stimuli, face identity aftereffects in
      children with autism were significantly reduced relative to typical children.
      This finding challenges the notion that atypicalities in the quality and/or
      quantity of children's attention during adaptation might account for group
      differences previously observed in this paradigm. Additionally, evidence of
      diminished face identity aftereffects despite a stimulus size change supports an
      adaptive processing atypicality in autism that extends beyond low-level,
      retinotopically coded stimulus properties. These findings support the notion that
      diminished face aftereffects in autism reflect atypicalities in adaptive norm
      based coding, which could also contribute to face processing difficulties in this
      group. 

PMID- 24312294
TI  - The venom gland transcriptome of Latrodectus tredecimguttatus revealed by deep
      sequencing and cDNA library analysis.
AB  - Latrodectus tredecimguttatus, commonly known as black widow spider, is well known
      for its dangerous bite. Although its venom has been characterized extensively,
      some fundamental questions about its molecular composition remain unanswered. The
      limited transcriptome and genome data available prevent further understanding of
      spider venom at the molecular level. In the present study, we combined next
      generation sequencing and conventional DNA sequencing to construct a venom gland
      transcriptome of the spider L. tredecimguttatus, which resulted in the
      identification of 9,666 and 480 high-confidence proteins among 34,334 de novo
      sequences and 1,024 cDNA sequences, respectively, by assembly, translation,
      filtering, quantification and annotation. Extensive functional analyses of these
      proteins indicated that mRNAs involved in RNA transport and spliceosome, protein
      translation, processing and transport were highly enriched in the venom gland,
      which is consistent with the specific function of venom glands, namely the
      production of toxins. Furthermore, we identified 146 toxin-like proteins forming
      12 families, including 6 new families in this spider in which alpha-LTX-Lt1a
      family2 is firstly identified as a subfamily of alpha-LTX-Lt1a family. The toxins
      were classified according to their bioactivities into five categories that
      functioned in a coordinate way. Few ion channels were expressed in venom gland
      cells, suggesting a possible mechanism of protection from the attack of their own
      toxins. The present study provides a gland transcriptome profile and extends our
      understanding of the toxinome of spiders and coordination mechanism for toxin
      production in protein expression quantity. 

PMID- 24312295
TI  - Profiling mRNAs of two Cuscuta species reveals possible candidate transcripts
      shared by parasitic plants.
AB  - Dodders are among the most important parasitic plants that cause serious yield
      losses in crop plants. In this report, we sought to unveil the genetic basis of
      dodder parasitism by profiling the trancriptomes of Cuscuta pentagona and C.
      suaveolens, two of the most common dodder species using a next-generation RNA
      sequencing platform. De novo assembly of the sequence reads resulted in more than
      46,000 isotigs and contigs (collectively referred to as expressed sequence tags
      or ESTs) for each species, with more than half of them predicted to encode
      proteins that share significant sequence similarities with known proteins of non
      parasitic plants. Comparing our datasets with transcriptomes of 12 other fully
      sequenced plant species confirmed a close evolutionary relationship between
      dodder and tomato. Using a rigorous set of filtering parameters, we were able to
      identify seven pairs of ESTs that appear to be shared exclusively by parasitic
      plants, thus providing targets for tailored management approaches. In addition,
      we also discovered ESTs with sequences similarities to known plant viruses,
      including cryptic viruses, in the dodder sequence assemblies. Together this study
      represents the first comprehensive transcriptome profiling of parasitic plants in
      the Cuscuta genus, and is expected to contribute to our understanding of the
      molecular mechanisms of parasitic plant-host plant interactions. 

PMID- 24312296
TI  - Comparing the ecological impacts of wind and oil & gas development: a landscape
      scale assessment.
AB  - Energy production in the United States is in transition as the demand for clean
      and domestic power increases. Wind energy offers the benefit of reduced
      emissions, yet, like oil and natural gas, it also contributes to energy sprawl.
      We used a diverse set of indicators to quantify the ecological impacts of oil,
      natural gas, and wind energy development in Colorado and Wyoming. Aerial imagery
      was supplemented with empirical data to estimate habitat loss, fragmentation,
      potential for wildlife mortality, susceptibility to invasion, biomass carbon
      lost, and water resources. To quantify these impacts we digitized the land-use
      footprint within 375 plots, stratified by energy type. We quantified the change
      in impacts per unit area and per unit energy produced, compared wind energy to
      oil and gas, and compared landscapes with and without energy development. We
      found substantial differences in impacts between energy types for most
      indicators, although the magnitude and direction of the differences varied. Oil
      and gas generally resulted in greater impacts per unit area but fewer impacts per
      unit energy compared with wind. Biologically important and policy-relevant
      outcomes of this study include: 1) regardless of energy type, underlying land-use
      matters and development in already disturbed areas resulted in fewer total
      impacts; 2) the number and source of potential mortality varied between energy
      types, however, the lack of robust mortality data limits our ability to use this
      information to estimate and mitigate impacts; and 3) per unit energy produced,
      oil and gas extraction was less impactful on an annual basis but is likely to
      have a much larger cumulative footprint than wind energy over time. This rapid
      evaluation of landscape-scale energy development impacts could be replicated in
      other regions, and our specific findings can help meet the challenge of balancing
      land conservation with society's demand for energy. 

PMID- 24312297
TI  - Liver accumulation of Plasmodium chabaudi-infected red blood cells and modulation
      of regulatory T cell and dendritic cell responses.
AB  - It is postulated that accumulation of malaria-infected Red Blood Cells (iRBCs) in
      the liver could be a parasitic escape mechanism against full destruction by the
      host immune system. Therefore, we evaluated the in vivo mechanism of this
      accumulation and its potential immunological consequences. A massive liver
      accumulation of P. c. chabaudi AS-iRBCs (Pc-iRBCs) was observed by intravital
      microscopy along with an over expression of ICAM-1 on day 7 of the infection, as
      measured by qRT-PCR. Phenotypic changes were also observed in regulatory T cells
      (Tregs) and dendritic cells (DCs) that were isolated from infected livers, which
      indicate a functional role for Tregs in the regulation of the liver inflammatory
      immune response. In fact, the suppressive function of liver-Tregs was in vitro
      tested, which demonstrated the capacity of these cells to suppress naive T cell
      activation to the same extent as that observed for spleen-Tregs. On the other
      hand, it is already known that CD4+ T cells isolated from spleens of protozoan
      parasite-infected mice are refractory to proliferate in vivo. In our experiments,
      we observed a similar lack of in vitro proliferative capacity in liver CD4+ T
      cells that were isolated on day 7 of infection. It is also known that nitric
      oxide and IL-10 are partially involved in acute phase immunosuppression; we found
      high expression levels of IL-10 and iNOS mRNA in day 7-infected livers, which
      indicates a possible role for these molecules in the observed immune suppression.
      Taken together, these results indicate that malaria parasite accumulation within
      the liver could be an escape mechanism to avoid sterile immunity sponsored by a
      tolerogenic environment. 

PMID- 24312298
TI  - Morphological and behavioral impact of AAV2/5-mediated overexpression of human
      wildtype alpha-synuclein in the rat nigrostriatal system.
AB  - The discovery of the involvement of alpha-synuclein (alpha-syn) in Parkinson's
      disease (PD) pathogenesis has resulted in the development and use of viral vector
      mediated alpha-syn overexpression rodent models. The goal of these series of
      experiments was to characterize the neurodegeneration and functional deficits
      resulting from injection of recombinant adeno-associated virus (rAAV) serotype
      2/5-expressing human wildtype alpha-syn in the rat substantia nigra (SN). Rats
      were unilaterally injected into two sites in the SN with either rAAV2/5
      expressing green fluorescent protein (GFP, 1.2 x 10(13)) or varying titers (2.2 x
      10(12), 1.0 x 10(13), 5.9 x 10(13), or 1.0 x 10(14)) of rAAV2/5-alpha-syn.
      Cohorts of rats were euthanized 4, 8, or 12 weeks following vector injection. The
      severity of tyrosine hydroxylase immunoreactive (THir) neuron death in the SN
      pars compacta (SNpc) was dependent on vector titer. An identical magnitude of
      nigrostriatal degeneration (60-70% SNpc THir neuron degeneration and 40-50% loss
      of striatal TH expression) was observed four weeks following 1.0 x 10(14) titer
      rAAV2/5-alpha-syn injection and 8 weeks following 1.0 x 10(13) titer rAAV2/5
      alpha-syn injection. THir neuron degeneration was relatively uniform throughout
      the rostral-caudal axis of the SNpc. Despite equivalent nigrostriatal
      degeneration between the 1.0 x 10(13) and 1.0 x 10(14) rAAV2/5-alpha-syn groups,
      functional impairment in the cylinder test and the adjusting steps task was only
      observed in rats with the longer 8 week duration of alpha-syn expression. Motor
      impairment in the cylinder task was highly correlated to striatal TH loss.
      Further, 8 weeks following 5.9 x 10(13) rAAV2/5-alpha-syn injection deficits in
      ultrasonic vocalizations were observed. In conclusion, our rAAV2/5-alpha-syn
      overexpression model demonstrates robust nigrostriatal alpha-syn overexpression,
      induces significant nigrostriatal degeneration that is both vector and duration
      dependent and under specific parameters can result in motor impairment that
      directly relates to the level of striatal TH denervation. 

PMID- 24312299
TI  - Serological response of patients with influenza A (H1N1) pdm09-associated
      pneumonia: an observational study.
AB  - BACKGROUND: Little is known about the dynamics or magnitude of antibody response
      in patients with influenza A (H1N1) pdm09-associated pneumonia. We described and
      compared the antibody response to influenza A (H1N1) pdm09 in patients with and
      without pneumonia. METHODS: We collected serum samples and determined antibody
      titers by the hemagglutination inhibition (HI) and microneutralization (mNT)
      assays from patients with RT-PCR confirmed influenza A (H1N1) pdm09 virus at
      baseline, 1, 2 and 6 months after onset of illness. RESULTS: Fifty-nine patients
      were enrolled, 45 (76.3%) were between 15 and 60 years of age, 49 (83.1%) were
      hospitalized and 25 (42.4%) had complications with pneumonia. Ninety-four percent
      of patients had HI titers >= 1: 40 and 90% had mNT titers >= 1: 160 at 2 months
      after illness. Geometric mean titers (GMT) of HI and mNT increased significantly
      (p<0.001) between baseline and months 1 or 2, then declined significantly
      (p<0.001) at month 6 by the HI assay, but dropped to an insignificant level
      (p=0.24) by the mNT assay. The mNT-GMT was at least twice as high as
      corresponding HI antibodies over a 6 month period. The GMT of HI and mNT in those
      with pneumonia (1 mo) peaked earlier than that of those without pneumonia (2 mo).
      When adjusted by age and gender, those with pneumonia had a higher HI-GMT than
      those without pneumonia at 1 month (264 vs. 117, p=0.007), 2 months (212 vs. 159,
      p=0.013), and 6 months (160 vs. 82, p=0.018). CONCLUSIONS: The patients recovered
      from influenza A (H1N1) pdm09-associated pneumonia, clearly developed an earlier
      and more robust antibody response until 6 months after onset of illness. The
      results in our study are useful to determine an appropriate donor and timing to
      obtain convalescent plasma for adjunctive treatment of seriously ill patients
      with pandemic H1N1 influenza.

PMID- 24312300
TI  - LncRNAs expression in preeclampsia placenta reveals the potential role of LncRNAs
      contributing to preeclampsia pathogenesis.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) are an important class of pervasive
      genes involved in a variety of biological functions. They are aberrantly
      expressed in many types of diseases. In this study, we aimed to investigate the
      lncRNA profiles in preeclampsia. Preeclampsia has been observed in patients with
      molar pregnancy where a fetus is absent, which demonstrate that the placenta is
      sufficient to cause this condition. Thus, we analyzed the lncRNA profiles in
      preeclampsia placentas. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      described the lncRNA profiles in six preeclampsia placentas (T) and five normal
      pregnancy placentas (N) using microarray. With abundant and varied probes
      accounting for 33,045 LncRNAs in our microarray, 28,443 lncRNAs that were
      expressed at a specific level were detected. From the data, we found 738 lncRNAs
      that were differentially expressed (>= 1.5-fold-change) among preeclampsia
      placentas compared with controls. Coding-non-coding gene co-expression networks
      (CNC network) were constructed based on the correlation analysis between the
      differentially expressed lncRNAs and mRNAs. According to the CNC network and GO
      analysis of differentially expressed lncRNAs/mRNAs, we selected three lncRNAs to
      analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100,
      and CEACAMP8 were evaluated using qPCR in 40 preeclampsia placentas and 40
      controls. These results revealed that three lncRNAs were aberrantly expressed in
      preeclampsia placentas compared with controls. CONCLUSIONS/SIGNIFICANCE: Our
      study is the first study to determine the genome-wide lncRNAs expression patterns
      in preeclampsia placenta using microarray. These results revealed that clusters
      of lncRNAs were aberrantly expressed in preeclampsia placenta compared with
      controls, which indicated that lncRNAs differentially expressed in preeclampsia
      placenta might play a partial or key role in preeclampsia development.
      Misregulation of LOC391533, LOC284100, and CEACAMP8 might contribute to the
      mechanism underlying preeclampsia. Taken together, this study may provide
      potential targets for the future treatment of preeclampsia and novel insights
      into preeclampsia biology.

PMID- 24312301
TI  - Next generation sequencing uncovers unexpected bacterial pathogens in ticks in
      western Europe.
AB  - BACKGROUND AND AIMS: Ticks are highly susceptible to global environmental and
      socio-economical changes. Several tick-borne pathogens have been reported in new
      geographical regions while new species, strains or genetic variants of tick-borne
      microorganisms are continually being detected. However, tick-borne pathogens are
      still poorly understood, and it is estimated that half of all human tick-borne
      disease has an unknown origin. Therefore in order to prevent these diseases, more
      effort is required to identify unknown or unexpected tick-borne pathogens. Ixodes
      ricinus is the vector for a broad range of bacterial pathogens and the most
      prevalent tick in Europe. The aim of the present study was to evaluate the
      capability of Next Generation Sequencing (NGS) to extend the inventory of
      pathogenic bacteria carried by this species of tick in France. METHODS: RNA and
      DNA were extracted from 1450 I. ricinus questing nymphs collected by flagging in
      Alsace, France. RNA was pooled and used for NGS. Following de novo assembly,
      bacterial contigs were assigned to the closest known taxonomy. DNA was used for
      real time PCR to confirm taxonomic species assignment of NGS-derived contigs for
      the doubtful cases, and for determination of prevalence. RESULTS: We have
      generated a global in-depth picture of tick-borne bacteria. We identified RNA
      from the main pathogenic bacterial species known to be transmitted by I. ricinus.
      In addition we also identified unanticipated bacterial species for which we have
      estimated the prevalence within those ticks inhabiting the studied areas.
      CONCLUSIONS: The data obtained from this study has proven that NGS has an
      enormous potential to detect the unexpected and provides the means to monitor
      pathogen occurrence.

PMID- 24312302
TI  - Dendritic cell-specific delivery of Flt3L by coronavirus vectors secures
      induction of therapeutic antitumor immunity.
AB  - Efficacy of antitumor vaccination depends to a large extent on antigen targeting
      to dendritic cells (DCs). Here, we assessed antitumor immunity induced by
      attenuated coronavirus vectors which exclusively target DCs in vivo and express
      either lymphocyte- or DC-activating cytokines in combination with a GFP-tagged
      model antigen. Tracking of in vivo transduced DCs revealed that vectors encoding
      for Fms-like tyrosine kinase 3 ligand (Flt3L) exhibited a higher capacity to
      induce DC maturation compared to vectors delivering IL-2 or IL-15. Moreover,
      Flt3L vectors more efficiently induced tumor-specific CD8(+) T cells, expanded
      the epitope repertoire, and provided both prophylactic and therapeutic tumor
      immunity. In contrast, IL-2- or IL-15-encoding vectors showed a substantially
      lower efficacy in CD8(+) T cell priming and failed to protect the host once
      tumors had been established. Thus, specific in vivo targeting of DCs with
      coronavirus vectors in conjunction with appropriate conditioning of the
      microenvironment through Flt3L represents an efficient strategy for the
      generation of therapeutic antitumor immunity. 

PMID- 24312303
TI  - Personal and household hygiene, environmental contamination, and health in
      undergraduate residence halls in New York City, 2011.
AB  - BACKGROUND: While several studies have documented the importance of hand washing
      in the university setting, the added role of environmental hygiene remains poorly
      understood. The purpose of this study was to characterize the personal and
      environmental hygiene habits of college students, define the determinants of
      hygiene in this population, and assess the relationship between reported hygiene
      behaviors, environmental contamination, and health status. METHODS: 501
      undergraduate students completed a previously validated survey assessing baseline
      demographics, hygiene habits, determinants of hygiene, and health status. Sixty
      survey respondents had microbiological samples taken from eight standardized
      surfaces in their dormitory environment. Bacterial contamination was assessed
      using standard quantitative bacterial culture techniques. Additional culturing
      for coagulase-positive Staphylococcus and coliforms was performed using selective
      agar. RESULTS: While the vast majority of study participants (n = 461, 92%)
      believed that hand washing was important for infection prevention, there was a
      large amount of variation in reported personal hygiene practices. More women than
      men reported consistent hand washing before preparing food (p = .002) and after
      using the toilet (p = .001). Environmental hygiene showed similar variability
      although 73.3% (n = 367) of subjects reported dormitory cleaning at least once
      per month. Contamination of certain surfaces was common, with at least one third
      of all bookshelves, desks, refrigerator handles, toilet handles, and bathroom
      door handles positive for >10 CFU of bacteria per 4 cm(2) area. Coagulase
      positive Staphylococcus was detected in three participants' rooms (5%) and
      coliforms were present in six students' rooms (10%). Surface contamination with
      any bacteria did not vary by frequency of cleaning or frequency of illness
      (p>.05). CONCLUSIONS: Our results suggest that surface contamination, while
      prevalent, is unrelated to reported hygiene or health in the university setting.
      Further research into environmental reservoirs of infectious diseases may
      delineate whether surface decontamination is an effective target of hygiene
      interventions in this population.

PMID- 24312304
TI  - Bathymetric variation in recruitment and relative importance of pre- and post
      settlement processes in coral assemblages at Lyudao (Green Island), Taiwan.
AB  - Studies on coral communities have typically been conducted in shallow waters (~5
      m). However, in the face of climate change, and as shallow coral communities
      become degraded, a greater understanding of deeper coral communities is needed as
      they become the main reef remnants, playing a central role in the future of coral
      reefs. To understand the dynamics of deeper coral assemblages, the recruitment
      and taxonomic composition of different life-stages at 5 and 15 m depths were
      compared at three locations in Lyudao, southeastern Taiwan in 2010. Coral
      recruits (<1 cm diameter, <4 months old) were examined using settlement plates.
      Juvenile corals (1-5 cm, several years old) were examined with quadrats, and
      adult corals (>5 cm, several years to decades old) were examined using transect
      lines. Pocilloporid and poritid corals had similar and higher numbers of recruits
      at 5 m compared to 15 m, whereas acroporid recruits were more abundant at 15 m.
      The primary cause for the former may be larval behavior, such that they position
      themselves in shallow waters, while that for the latter may be the dominance of
      brooding acroporid species (Isopora spp.) at 15 m. The taxonomic composition,
      especially between recruits and juveniles/adults, was more similar at 15 m than
      at 5 m. These results suggest a change in the relative importance of pre- and
      post-settlement processes in assemblage determinants with depth; coral
      assemblages in shallow habitats (more disturbed) are more influenced by post
      settlement processes (mortality events), while those in deeper habitats (more
      protected) are more influenced by pre-settlement processes (larval supply). 

PMID- 24312305
TI  - The potential of antimicrobials to induce thrombocytopenia in critically ill
      patients: data from a randomized controlled trial.
AB  - BACKGROUND: Antimicrobial-induced thrombocytopenia is frequently described in the
      literature among critically ill patients. Several antimicrobials have been
      implicated, although experimental evidence to demonstrate causality is limited.
      We report, using a randomized trial, the potential of antimicrobials to induce
      thrombocytopenia. METHODS: Randomized trial allocated patients to antimicrobial
      treatment according to standard- of-care (SOC group) or drug-escalation in case
      of procalcitonin increases (high-exposure group). Patients were followed until
      death or day 28. Thrombocytopenia defined as absolute (platelet count <= 100 x
      109/L) or relative (>= 20% decrease in platelet count). Analyses were performed
      in the two randomized groups and as a merged cohort. RESULTS: Of the 1147
      patients with platelet data available, 18% had absolute thrombocytopenia within
      the first 24 hours after admission to intensive care unit and additional 17%
      developed this complication during follow-up; 57% developed relative
      thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4
      was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71
      [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure
      group received more antimicrobials including piperacillin/tazobactam, meropenem
      and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more
      frequently in the SOC group (p<0.05). Risk of absolute and relative
      thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06;
      respectively), as well as absolute platelet count (daily difference, high
      exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In
      observational analyses, use of ciprofloxacin and piperacillin/tazobactam
      predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48
      2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were
      associated with a reduction in absolute platelet count (p=0.0005). CONCLUSION:
      High exposure to broad-spectrum antimicrobials does not result in a reduction in
      thrombocytopenia in critically ill patients. However, single use of
      ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower
      platelet count. TRIAL REGISTRATION: ClinicalTrials.gov NCT00271752
      http://clinicaltrials.gov/ct2/show/NCT00271752.

PMID- 24312306
TI  - A dexamethasone prodrug reduces the renal macrophage response and provides
      enhanced resolution of established murine lupus nephritis.
AB  - We evaluated the ability of a macromolecular prodrug of dexamethasone (P-Dex) to
      treat lupus nephritis in (NZB * NZW)F1 mice. We also explored the mechanism
      underlying the anti-inflammatory effects of this prodrug. P-Dex eliminated
      albuminuria in most (NZB * NZW)F1 mice. Furthermore, P-Dex reduced the incidence
      of severe nephritis and extended lifespan in these mice. P-Dex treatment also
      prevented the development of lupus-associated hypertension and vasculitis.
      Although P-Dex did not reduce serum levels of anti-dsDNA antibodies or glomerular
      immune complexes, P-Dex reduced macrophage recruitment to the kidney and
      attenuated tubulointerstitial injury. In contrast to what was observed with free
      dexamethasone, P-Dex did not induce any deterioration of bone quality. However, P
      Dex did lead to reduced peripheral white blood cell counts and adrenal gland
      atrophy. These results suggest that P-Dex is more effective and less toxic than
      free dexamethasone for the treatment of lupus nephritis in (NZB * NZW)F1 mice.
      Furthermore, the data suggest that P-Dex may treat nephritis by attenuating the
      renal inflammatory response to immune complexes, leading to decreased immune cell
      infiltration and diminished renal inflammation and injury. 

PMID- 24312307
TI  - Prognostic value of EZH2 expression and activity in renal cell carcinoma: a
      prospective study.
AB  - Increased expression of EZH2 correlates with aggressive clinical behavior in
      various malignancies. In this study, we aim to investigate the clinical and
      prognostic values of EZH2 expression and activity in tumor tissues and improve
      the risk stratification in patients with renal cell carcinoma after surgery. We
      analyzed EZH2 expression and its activity as indicated by H3K27me3 levels
      comprising 373 patients with renal cell carcinoma in our institute. Outcome was
      assessed as overall survival and disease free survival using Kaplan-Meier
      analysis. Prognostic values of EZH2 and H3K27me3 expression for clinical outcomes
      were evaluated by Cox regression analysis. We used receiver operating
      characteristic to calculate diagnostic accuracy. High EZH2 expression correlates
      with poor overall survival in all patients, especially in advanced RCC, which is
      an independent prognostic factor in disease free survival and overall survival.
      Compared with EZH2, H3K27me3 expression is not an independent prognostic factor.
      The expressions of H3K27me3 and EZH2 are not completely consistent, which might
      be due to complicated interaction of Polycomb Repressor Complex 2. A combination
      of EZH2 expression and TNM stage could have better prognostic value than do TNM
      stage or EZH2 expression alone in both sets for disease free survival and overall
      survival. These results imply that evaluating intratumoral EZH2 density might
      improve prognostic value to the TNM staging system and inform treatment decisions
      for patients with late-stage renal cell carcinoma. 

PMID- 24312308
TI  - Use of thiopurines and risk of colorectal neoplasia in patients with inflammatory
      bowel diseases: a meta-analysis.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD) is commonly treated with thiopurines
      such as azathioprine and mercaptopurine for the maintenance of remission. Studies
      examining chemopreventive of these medications on colorectal neoplasm in IBD
      patients have yielded conflicting results. We performed a meta-analysis to assess
      the role of thiopurines for this indication. METHODS: We performed a systematic
      search of PubMed, Web of Science, EMBASE and Cochrane to identify studies
      reporting colorectal neoplasm from IBD patients treated with thiopurines and
      conducted a meta-analysis of pooled relative risk (RR) using the random effects
      model. RESULTS: Nine case-control and ten cohort studies fulfilled the inclusion
      criteria. The use of thiopurines was associated with a statistically significant
      decreased incidence of colorectal neoplasm (summary RR=0.71, 95% CI=0.54-0.94,
      p=0.017), even after adjustment for duration and extent of the disease, but there
      was high heterogeneity among studies (I(2)=68.0%, p<0.001). The RR of advanced
      neoplasm (high-grade dysplasia and cancer) was 0.72 (95%CI=0.50-1.03, p=0.070)
      and that of cancer was 0.70 (95% CI=0.46-1.09, p=0.111) for thiopurine-treated
      patients. Heterogeneity of the studies was affected by the sample size (</>= 100
      cases) and whether the patients had longstanding colitis (>= 7 years).
      CONCLUSION: The current meta-analysis revealed that thiopurines had a
      chemopreventive effect of colorectal neoplasms and a tendency of reducing
      advanced colorectal neoplasms in IBD. Due to the heterogeneity of included
      studies, these results should be interpreted with caution.

PMID- 24312310
TI  - Ecophysiological and anatomical mechanisms behind the nurse effect: which are
      more important? A multivariate approach for cactus seedlings.
AB  - BACKGROUND: Cacti establish mostly occurs under the canopy of nurse plants which
      provide a less stressful micro-environment, although mechanisms underlying this
      process are unknown. The impact of the combination of light and watering
      treatments on Opuntia streptacantha (Cactaceae) seedlings was examined.
      METHODS/PRINCIPAL FINDINGS: Ecophysiological [titratable acidity, osmotic
      potential ('solute potential', Psis ), relative growth rate (RGR) and their
      components (NAR, SLA, and LWR)], anatomical (chloroplast density, chloroplast
      frequency, and cell area), and environmental [photosynthetic photon flux density
      (PPFD) and air temperature] sets of variables were analyzed, assessing
      relationships between them and measuring the intensity of the relationships.
      Three harvests were carried out at days 15, 30, and 45. Psis and acidity content
      were the most important responses for seedling establishment. The main anatomical
      and environmental variables were chloroplast density and water availability,
      respectively. Opuntia streptacantha seedlings establish better in the shade
      watering treatment, due to higher Psis and acidity, unaffected chloroplasts, and
      lower PPFD. In addition, the chloroplasts of cells under high-light and non
      watering treatment were clumped closer to the center of the cytosol than those
      under shade-drought, to avoid photoinhibition and/or to better distribute or
      utilize the penetrating light in the green plant tissue. CONCLUSIONS: Opuntia
      seedlings grow better under the shade, although they can tolerate drought in open
      spaces by increasing and moving chloroplasts and avoiding drastic decreases in
      their Psis . This tolerance could have important implications for predicting the
      impact of climate change on natural desert regeneration, as well as for planning
      reforestation-afforestation practices, and rural land uses.

PMID- 24312309
TI  - A dietary supplementation with leucine and antioxidants is capable to accelerate
      muscle mass recovery after immobilization in adult rats.
AB  - Prolonged inactivity induces muscle loss due to an activation of proteolysis and
      decreased protein synthesis; the latter is also involved in the recovery of
      muscle mass. The aim of the present work was to explore the evolution of muscle
      mass and protein metabolism during immobilization and recovery and assess the
      effect of a nutritional strategy for counteracting muscle loss and facilitating
      recovery. Adult rats (6-8 months) were subjected to unilateral hindlimb casting
      for 8 days (I0-I8) and then permitted to recover for 10 to 40 days (R10-R40).
      They were fed a Control or Experimental diet supplemented with
      antioxidants/polyphenols (AOX) (I0 to I8), AOX and leucine (AOX + LEU) (I8 to
      R15) and LEU alone (R15 to R40). Muscle mass, absolute protein synthesis rate and
      proteasome activities were measured in gastrocnemius muscle in casted and non
      casted legs in post prandial (PP) and post absorptive (PA) states at each time
      point. Immobilized gastrocnemius protein content was similarly reduced (-37%) in
      both diets compared to the non-casted leg. Muscle mass recovery was accelerated
      by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P<0.05 at R40) due
      to a higher protein synthesis both in PA and PP states (+23% and 31%
      respectively, Experimental vs. Control diets, P<0.05, R40) without difference in
      trypsin- and chymotrypsin-like activities between diets. Thus, this nutritional
      supplementation accelerated the recovery of muscle mass via a stimulation of
      protein synthesis throughout the entire day (in the PP and PA states) and could
      be a promising strategy to be tested during recovery from bed rest in humans. 

PMID- 24312311
TI  - NEDD4L is downregulated in colorectal cancer and inhibits canonical WNT
      signaling.
AB  - The NEDD4 family of E3 ubiquitin ligases includes nine members. Each is a modular
      protein, containing an N-terminal C2 domain for cell localization, two-to-four
      central WW domains for substrate recognition, and a C-terminal, catalytic HECT
      domain, which is responsible for catalyzing the ubiquitylation reaction. Members
      of this family are known to affect pathways central to the pathogenesis of
      colorectal cancer, including the WNT, TGFbeta, EGFR, and p53 pathways. Recently,
      NEDD4 mRNA was reported to be overexpressed in colorectal cancer, but tumor stage
      was not considered in the analysis. Expression of the other family members has
      not been studied in colorectal cancer. Herein, we determined the expression
      patterns of all nine NEDD4 family members in 256 patients who presented with
      disease ranging from premalignant adenoma to stage IV colorectal cancer. NEDD4
      mRNA was significantly increased in all stages of colorectal cancer. In contrast,
      NEDD4L mRNA, the closest homolog to NEDD4, was the most highly downregulated
      family member, and was significantly downregulated in all tumor stages. We also
      found NEDD4L protein was significantly decreased by western blotting in
      colorectal cancer samples compared to adjacent normal mucosa. In addition,
      NEDD4L, but not catalytically inactive NEDD4L, inhibited canonical WNT signaling
      at or below the level of beta-catenin in vitro. These findings suggest that
      NEDD4L may play a tumor suppressive role in colorectal cancer, possibly through
      inhibition of canonical WNT signaling. 

PMID- 24312312
TI  - Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with
      bladder cancer risk.
AB  - PURPOSE: miRNAs can regulate the biological processes, including differentiation,
      proliferation and apoptosis. DICER and DROSHA are two members of RNase III
      family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study,
      we hypothesized that genetic variations of the DICER and DROSHA genes were
      associated with the bladder cancer risk. EXPERIMENTAL DESIGN: We performed a case
      control study of 685 bladder cancer cases and 730 controls to investigate the
      association between the seven functional SNPs of DICER and DROSHA genes and
      bladder cancer risk. We then evaluated the functionality of the important SNPs.
      RESULTS: We found that rs10719T>C polymorphism located in 3' untranslated region
      (UTR) of DROSHA gene was associated with the increased risk of bladder cancer.
      Stratified analysis suggested that rs10719TC/CC genotype can increase risk of
      bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P =
      0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype.
      Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding
      activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719
      T to G substitution disrupted the binding site for hsa-miR-27b, resulting the
      increased levels of DROSHA protein. CONCLUSIONS: Taken together, these findings
      suggested that DROSHA rs10719T>C polymorphism may be associated with bladder
      cancer risk in a Chinese population, and hsa-miR-27b can influence the expression
      of DROSHA protein by binding with 3'UTR.

PMID- 24312313
TI  - Comparison of diagnostic value of conventional ultrasonography and shear wave
      elastography in the prediction of thyroid lesions malignancy.
AB  - INTRODUCTION: Thyroid nodular disease (TND) is a very common disorder. However,
      since the rate of malignancy is reported to be 3-10%, only a minority of patients
      require aggressive surgical treatment. As a result, there is a need for
      diagnostic tools which would allow for a reliable differentiation between benign
      and malignant nodules. Although a number of conventional ultrasonographic (US)
      features are proved to be markers of malignancy, Shear Wave Elastography (SWE) is
      considered to be an improvement of conventional US. The aim of this study was to
      compare conventional US markers and SWE diagnostic values in the differentiation
      of benign and malignant thyroid nodules. MATERIALS AND METHODS: All patients
      referred for thyroidectomy, irrespective of the indications, underwent a US
      thyroid examination prospectively. Patients with TND were included into the
      study. Results of the US and SWE examinations were compared with post-surgical
      histopathology. RESULTS: One hundred and twenty two patients with 393 thyroid
      nodules were included into the study. Twenty two patients were diagnosed with
      cancer. SWE turned out to be a predictor of malignancy superior to any other
      conventional US markers (OR=54.5 using qualitative scales and 40.8 using
      quantitative data on maximal stiffness with a threshold of 50 kPa). CONCLUSIONS:
      Although most conventional US markers of malignancy prove to be significant, none
      of them are characterized by both high sensitivity and specificity. SWE seems to
      be an important step forward, allowing for a more reliable distinction of benign
      and malignant thyroid nodules. Our study, assessing SWE properties on the highest
      number of thyroid lesions at the time of publication, confirms the high
      diagnostic value of this technique. It also indicates that a quantitative
      evaluation of thyroid lesions is not superior to simpler qualitative methods.

PMID- 24312314
TI  - Antigenic analysis of monoclonal antibodies against different epitopes of sigmaB
      protein of avian reovirus.
AB  - BACKGROUND: Avian reovirus (ARV) causes arthritis, tenosynovitis, runting
      stunting syndrome (RSS), malabsorption syndrome (MAS) and immunosuppression in
      chickens. sigmaB is one of the major structural proteins of ARV, which is able to
      induce group-specific antibodies against the virus. METHODS AND RESULTS: The
      present study described the identification of two linear B-cell epitopes in ARV
      sigmaB through expressing a set of partially overlapping and consecutive
      truncated peptides spanning sigmaB screened with two monoclonal antibodies (mAbs)
      1F4 and 1H3-1.The data indicated that (21)KTPACW(26) (epitope A) and
      (32)WDTVTFH(38) (epitope B) were minimal determinants of the linear B cell
      epitopes. Antibodies present in the serum of ARV-positive chickens recognized the
      minimal linear epitopes in Western blot analyses. By sequence alignment analysis,
      we determined that the epitopes A and B were not conserved among ARV, duck
      reovirus (DRV) and turkey reovirus (TRV) strains. Western blot assays, confirmed
      that epitopes A and B were ARV-specific epitopes, and they could not react with
      the corresponding peptides of DRV and TRV. CONCLUSIONS AND SIGNIFICANCE: We
      identified (21)KTPACW(26) and (32)WDTVTFH(38) as sigmaB -specific epitopes
      recognized by mAbs 1F4 and 1H3-1, respectively. The results in this study may
      have potential applications in development of diagnostic techniques and epitope
      based marker vaccines against ARV groups.

PMID- 24312315
TI  - Affective instability in daily life is predicted by resting heart rate
      variability.
AB  - Previous research has shown that being affectively unstable is an indicator of
      several forms of psychological maladjustment. However, little is known about the
      mechanisms underlying affective instability. Our research aims to examine the
      possibility that being prone to extreme fluctuations in one's feelings is related
      to maladaptive emotion regulation. We investigated this hypothesis by relating
      affective instability, assessed in daily life using the experience sampling
      method, to self-reported emotion regulation strategies and to parasympathetically
      mediated heart rate variability (HRV), a physiological indicator of emotion
      regulation capacity. Results showed that HRV was negatively related to
      instability of positive affect (as measured by mean square successive
      differences), indicating that individuals with lower parasympathetic tone are
      emotionally less stable, particularly for positive affect. 

PMID- 24312316
TI  - A computational model of a microfluidic device to measure the dynamics of oxygen
      dependent ATP release from erythrocytes.
AB  - Erythrocytes are proposed to be involved in blood flow regulation through both
      shear- and oxygen-dependent mechanisms for the release of adenosine triphosphate
      (ATP), a potent vasodilator. In a recent study, the dynamics of shear-dependent
      ATP release from erythrocytes was measured using a microfluidic device with a
      constriction in the channel to increase shear stress. The brief period of
      increased shear stress resulted in ATP release within 25 to 75 milliseconds
      downstream of the constriction. The long-term goal of our research is to apply a
      similar approach to determine the dynamics of oxygen-dependent ATP release. In
      the place of the constriction, an oxygen permeable membrane would be used to
      decrease the hemoglobin oxygen saturation of erythrocytes flowing through the
      channel. This paper describes the first stage in achieving that goal, the
      development of a computational model of the proposed experimental system to
      determine the feasibility of altering oxygen saturation rapidly enough to measure
      ATP release dynamics. The computational model was constructed based on
      hemodynamics, molecular transport of oxygen and ATP, kinetics of
      luciferin/luciferase reaction for reporting ATP concentrations, light absorption
      by hemoglobin, and sensor characteristics. A linear model of oxygen saturation
      dependent ATP release with variable time delay was used in this study. The
      computational results demonstrate that a microfluidic device with a 100 um deep
      channel will cause a rapid decrease in oxygen saturation over the oxygen
      permeable membrane that yields a measurable light intensity profile for a change
      in rate of ATP release from erythrocytes on a timescale as short as 25
      milliseconds. The simulation also demonstrates that the complex dynamics of ATP
      release from erythrocytes combined with the consumption by luciferin/luciferase
      in a flowing system results in light intensity values that do not simply
      correlate with ATP concentrations. A computational model is required for proper
      interpretation of experimental data. 

PMID- 24312317
TI  - The effect of a maturing antiretroviral program on early mortality for patients
      with advanced immune-suppression in Soweto, South Africa.
AB  - OBJECTIVE: We hypothesize that time to initiate care and maturity of a treatment
      program impact on outcome of severely immuno-compromised patients with higher
      risk of mortality. DESIGN: We conducted a retrospective cohort analysis at the
      Perinatal HIV Research Unit Adult ART clinic, Soweto, South Africa. METHODS:
      ELIGIBILITY CRITERIA FOR THIS ANALYSIS WERE: attendance for minimum one visit
      between August 2004 and August 2010, age >18 years, CD4 count < 50 cells/mm(3)
      and ART-naive at screening. We followed participants up to one year after ART
      initiation. We defined years 2004-2007 and 2008-2010 as the early and late eras
      respectively. Chi-square test and survival analysis methods were used for
      mortality comparisons between eras. RESULTS: Of 2357 patients eligible for
      antiretroviral treatment, 395 (17%) had CD4 counts < 50 cells/mm(3) and ART-naive
      at screening. Overall 261 (66%) were women. Patients had similar median age (35
      vs. 33.5 years, p=0.08), time to HAART initiation (7 days, p=0.18) and baseline
      CD4 count (20 vs. 23 cells/mm(3), p=0.5) between eras. Overall 63 (16%) patients
      died in their first year of treatment (2 per 100 person-months) and the main
      cause of death was tuberculosis (n=23, 37%). The proportion of deaths (52/262 vs.
      11/133, p=0.003) and time to death from enrolment (logrank p=0.04) were
      significantly different between eras. CONCLUSION: Mortality decreased as the ART
      program matured in Soweto while time to initiation of treatment remained similar
      in both eras. Because ART guidelines were consistent during both eras, it is
      possible that with time, management of patients improved as expertise was gained.

PMID- 24312318
TI  - mtDNA T8993G mutation-induced F1F0-ATP synthase defect augments mitochondrial
      dysfunction associated with hypoxia/reoxygenation: the protective role of
      melatonin.
AB  - BACKGROUND: F1F0-ATP synthase (F1F0-ATPase) plays important roles in regulating
      mitochondrial function during hypoxia, but the effect of F1F0-ATPase defect on
      hypoxia/reoxygenation (H/RO) is unknown. The aim of this study was to investigate
      how mtDNA T8993G mutation (NARP)-induced inhibition of F1F0-ATPase modulates the
      H/RO-induced mitochondrial dysfunction. In addition, the potential for melatonin,
      a potent antioxidant with multiple mitochondrial protective properties, to
      protect NARP cells exposed to H/RO was assessed. METHODS AND FINDINGS: NARP
      cybrids harboring 98% of mtDNA T8993G genes were established as an in vitro model
      for cells with F1F0-ATPase defect; their parental osteosarcoma 143B cells were
      studied for comparison. Treating the cells with H/RO using a hypoxic chamber
      resembles ischemia/reperfusion in vivo. NARP significantly enhanced apoptotic
      death upon H/RO detected by MTT assay and the trypan blue exclusion test of cell
      viability. Based on fluorescence probe-coupled laser scanning imaging microscopy,
      NARP significantly enhanced mitochondrial reactive oxygen species (mROS)
      formation and mitochondrial Ca(2+) (mCa(2+)) accumulation in response to H/RO,
      which augmented the depletion of cardiolipin, resulting in the retardation of
      mitochondrial movement. With stronger H/RO stress (either with longer
      reoxygenation duration, longer hypoxia duration, or administrating secondary
      oxidative stress following H/RO), NARP augmented H/RO-induced mROS formation to
      significantly depolarize mitochondrial membrane potential (DeltaPsim), and
      enhance mCa(2+) accumulation and nitric oxide formation. Also, NARP augmented
      H/RO-induced mROS oxidized and depleted cardiolipin, thereby promoting permanent
      mitochondrial permeability transition, retarded mitochondrial movement, and
      enhanced apoptosis. Melatonin markedly reduced NARP-augmented H/RO-induced mROS
      formation and therefore significantly reduced mROS-mediated depolarization of
      DeltaPsim and accumulation of mCa(2+), stabilized cardiolipin, and then improved
      mitochondrial movement and cell survival. CONCLUSION: NARP-induced inhibition of
      F1F0-ATPase enhances mROS formation upon H/RO, which augments the depletion of
      cardiolipin and retardation of mitochondrial movement. Melatonin may have the
      potential to rescue patients with ischemia/reperfusion insults, even those
      associated with NARP symptoms.

PMID- 24312319
TI  - Anti-Mullerian hormone recruits BMPR-IA in immature granulosa cells.
AB  - Anti-Mullerian hormone (AMH) is a member of the TGF-beta superfamily secreted by
      the gonads of both sexes. This hormone is primarily known for its role in the
      regression of the Mullerian ducts in male fetuses. In females, AMH is expressed
      in granulosa cells of developing follicles. Like other members of the TGF-beta
      superfamily, AMH transduces its signal through two transmembrane serine/threonine
      kinase receptors including a well characterized type II receptor, AMHR-II. The
      complete signalling pathway of AMH involving Smads proteins and the type I
      receptor is well known in the Mullerian duct and in Sertoli and Leydig cells but
      not in granulosa cells. In addition, few AMH target genes have been identified in
      these cells. Finally, while several co-receptors have been reported for members
      of the TGF-beta superfamily, none have been described for AMH. Here, we have
      shown that none of the Bone Morphogenetic Proteins (BMPs) co-receptors, Repulsive
      guidance molecules (RGMs), were essential for AMH signalling. We also
      demonstrated that the main Smad proteins used by AMH in granulosa cells were Smad
      1 and Smad 5. Like for the other AMH target cells, the most important type I
      receptor for AMH in these cells was BMPR-IA. Finally, we have identified a new
      AMH target gene, Id3, which could be involved in the effects of AMH on the
      differentiation of granulosa cells and its other target cells. 

PMID- 24312320
TI  - The genome sequence of 'Mycobacterium massiliense' strain CIP 108297 suggests the
      independent taxonomic status of the Mycobacterium abscessus complex at the
      subspecies level.
AB  - Members of the Mycobacterium abscessus complex are rapidly growing mycobacteria
      that are emerging as human pathogens. The M. abscessus complex was previously
      composed of three species, namely M. abscessus sensu stricto, 'M. massiliense',
      and 'M. bolletii'. In 2011, 'M. massiliense' and 'M. bolletii' were united and
      reclassified as a single subspecies within M. abscessus: M. abscessus subsp.
      bolletii. However, the placement of 'M. massiliense' within the boundary of M.
      abscessus subsp. bolletii remains highly controversial with regard to clinical
      aspects. In this study, we revisited the taxonomic status of members of the M.
      abscessus complex based on comparative analysis of the whole-genome sequences of
      53 strains. The genome sequence of the previous type strain of 'Mycobacterium
      massiliense' (CIP 108297) was determined using next-generation sequencing. The
      genome tree based on average nucleotide identity (ANI) values supported the
      differentiation of 'M. bolletii' and 'M. massiliense' at the subspecies level.
      The genome tree also clearly illustrated that 'M. bolletii' and 'M. massiliense'
      form a distinct phylogenetic clade within the radiation of the M. abscessus
      complex. The genomic distances observed in this study suggest that the current M.
      abscessus subsp. bolletii taxon should be divided into two subspecies, M.
      abscessus subsp. massiliense subsp. nov. and M. abscessus subsp. bolletii, to
      correspondingly accommodate the previously known 'M. massiliense' and 'M.
      bolletii' strains. 

PMID- 24312321
TI  - Asthma and pneumonia among children less than five years with acute respiratory
      symptoms in Mulago Hospital, Uganda: evidence of under-diagnosis of asthma.
AB  - BACKGROUND: Pneumonia is considered the major cause of mortality among children
      with acute respiratory disease in low-income countries but may be over-diagnosed
      at the cost of under-diagnosing asthma. We report the magnitude of asthma and
      pneumonia among "under-fives" with cough and difficulty breathing, based on
      stringent clinical criteria. We also describe the treatment for children with
      acute respiratory symptoms in Mulago Hospital. METHODS: We enrolled 614 children
      aged 2-59 months with cough and difficulty breathing. Interviews, physical
      examination, blood and radiological investigations were done. We defined asthma
      according to Global Initiative for Asthma guidelines. Pneumonia was defined
      according to World Health Organization guidelines, which were modified by
      including fever and white cell count, C-reactive protein, blood culture and chest
      x-ray. Children with asthma or bronchiolitis were collectively referred to as
      "asthma syndrome" due to challenges of differentiating the two conditions in
      young children. Three pediatricians reviewed each participant's case report post
      hoc and made a diagnosis according to the study criteria. RESULTS: Of the 614
      children, 41.2% (95% CI: 37.3-45.2) had asthma syndrome, 27.2% (95% CI: 23.7
      30.9) had bacterial pneumonia, 26.5% (95% CI: 23.1-30.2) had viral pneumonia,
      while 5.1% (95% CI: 3.5-7.1) had other diagnoses including tuberculosis. Only
      9.5% of the children with asthma syndrome had been previously diagnosed as
      asthma. Of the 253 children with asthma syndrome, 95.3% (95% CI: 91.9-97.5) had a
      prescription for antibiotics, 87.7% (95% CI: 83.1-91.5) for bronchodilators and
      43.1% (95% CI: 36.9-49.4) for steroids. CONCLUSION: Although reports indicate
      that acute respiratory symptoms in children are predominantly due to pneumonia,
      asthma syndrome contributes a significant proportion. Antibiotics are used
      irrationally due to misdiagnosis of asthma as pneumonia. There is need for better
      diagnostic tools for childhood asthma and pneumonia in Uganda.

PMID- 24312322
TI  - Understanding the causes of recent warming of mediterranean waters. How much
      could be attributed to climate change?
AB  - During the past two decades, Mediterranean waters have been warming at a rather
      high rate resulting in scientific and social concern. This warming trend is
      observed in satellite data, field data and model simulations, and affects both
      surface and deep waters throughout the Mediterranean basin. However, the warming
      rate is regionally different and seems to change with time, which has led to the
      question of what causes underlie the observed trends. Here, we analyze available
      satellite information on sea surface temperature (SST) from the last 25 years
      using spectral techniques and find that more than half of the warming tendency
      during this period is due to a non-linear, wave-like tendency. Using a state of
      the art hydrodynamic model, we perform a hindcast simulation and obtain the
      simulated SST evolution of the Mediterranean basin for the last 52 years. These
      SST results show a clear sinusoidal tendency that follows the Atlantic
      Multidecadal Oscillation (AMO) during the simulation period. Our results reveal
      that 58% of recent warming in Mediterranean waters could be attributed to this
      AMO-like oscillation, being anthropogenic-induced climate change only responsible
      for 42% of total trend. The observed acceleration of water warming during the
      1990s therefore appears to be caused by a superimposition of anthropogenic
      induced warming with the positive phase of the AMO, while the recent slowdown of
      this tendency is likely due to a shift in the AMO phase. It has been proposed
      that this change in the AMO phase will mask the effect of global warming in the
      forthcoming decades, and our results indicate that the same could also be
      applicable to the Mediterranean Sea. Henceforth, natural multidecadal temperature
      oscillations should be taken into account to avoid underestimation of the
      anthropogenic-induced warming of the Mediterranean basin in the future. 

PMID- 24312323
TI  - Anti-cancer activity of an osthole derivative, NBM-T-BMX-OS01: targeting vascular
      endothelial growth factor receptor signaling and angiogenesis.
AB  - Angiogenesis occurs during tissue growth, development and wound healing. It is
      also required for tumor progression and represents a rational target for
      therapeutic intervention. NBM-T-BMX-OS01 (BMX), derived from the semisynthesis of
      osthole, an active ingredient isolated from Chinese herb Cnidium monnieri (L.)
      Cuss., was recently shown to enhance learning and memory in rats. In this study,
      we characterized the anti-angiogenic activities of NBM-T-BMX-OS01 (BMX) in an
      effort to develop novel inhibitors to suppress angiogenesis and tumor growth. BMX
      inhibited vascular endothelial growth factor (VEGF)-induced proliferation,
      migration and endothelial tube formation in human umbilical endothelial cells
      (HUVECs). BMX also attenuated VEGF-induced microvessel sprouting from aortic
      rings ex vivo and reduced HCT116 colorectal cancer cells-induced angiogenesis in
      vivo. Moreover, BMX inhibited the phosphorylation of VEGFR2, FAK, Akt and ERK in
      HUVECs exposed to VEGF. BMX was also shown to inhibit HCT116 cell proliferation
      and to suppress the growth of subcutaneous xenografts of HCT116 cells in vivo.
      Taken together, this study provides evidence that BMX modulates vascular
      endothelial cell remodeling and leads to the inhibition of tumor angiogenesis.
      These results also support the role of BMX as a potential drug candidate and
      warrant the clinical development in the treatment of cancer. 

PMID- 24312324
TI  - PKCzeta mediates breakdown of outer blood-retinal barriers in diabetic
      retinopathy.
AB  - AIMS/HYPOTHESIS: Diabetic macular edema represents the main cause of visual loss
      in diabetic retinopathy. Besides inner blood retinal barrier breakdown, the role
      of the outer blood retinal barrier breakdown has been poorly analyzed. We
      characterized the structural and molecular alterations of the outer blood retinal
      barrier during the time course of diabetes, focusing on PKCzeta, a critical
      protein for tight junction assembly, known to be overactivated by hyperglycemia.
      METHODS: Studies were conducted on a type2 diabetes Goto-Kakizaki rat model.
      PKCzeta level and subcellular localization were assessed by immunoblotting and
      immunohistochemistry. Cell death was detected by TUNEL assays. PKCzeta level on
      specific layers was assessed by laser microdissection followed by Western
      blotting. The functional role of PKCzeta was then evaluated in vivo, using
      intraocular administration of its specific inhibitor. RESULTS: PKCzeta was
      localized in tight junction protein complexes of the retinal pigment epithelium
      and in photoreceptors inner segments. Strikingly, in outer segment PKCzeta
      staining was restricted to cone photoreceptors. Short-term hyperglycemia induced
      activation and delocalization of PKCzeta from both retinal pigment epithelium
      junctions and cone outer segment. Outer blood retinal barrier disruption and
      photoreceptor cone degeneration characterized long-term hyperglycemia. In vivo,
      reduction of PKCzeta overactivation using a specific inhibitor, restored its
      tight-junction localization and not only improved the outer blood retinal
      barrier, but also reduced photoreceptor cell-death. CONCLUSIONS: In the retina,
      hyperglycemia induced overactivation of PKCzeta is associated with outer blood
      retinal barrier breakdown and photoreceptor degeneration. In vivo, short-term
      inhibition of PKCzeta restores the outer barrier structure and reduces
      photoreceptor cell death, identifying PKCzeta as a potential target for early and
      underestimated diabetes-induced retinal pathology.

PMID- 24312326
TI  - High compliance with newborn community-to-facility referral in eastern Uganda:.an
      opportunity to improve newborn survival.
AB  - BACKGROUND: Seventy-five percent of newborn deaths happen in the first-week of
      life, with the highest risk of death in the first 24-hours after birth.WHO and
      UNICEF recommend home-visits for babies in the first-week of life to assess for
      danger-signs and counsel caretakers for immediate referral of sick newborns. We
      assessed timely compliance with newborn referrals made by community-health
      workers (CHWs), and its determinants in Iganga and Mayuge Districts in rural
      eastern Uganda. METHODS: A historical cohort study design was used to
      retrospectively follow up newborns referred to health facilities between
      September 2009 and August 2011. Timely compliance was defined as caretakers of
      newborns complying with CHWs' referral advice within 24-hours. RESULTS: A total
      of 724 newborns were referred by CHWs of whom 700 were successfully traced. Of
      the 700 newborns, 373 (53%) were referred for immunization and postnatal-care,
      and 327 (47%) because of a danger-sign. Overall, 439 (63%) complied, and of the
      327 sick newborns, 243 (74%) caretakers complied with the referrals. Predictors
      of referral compliance were; the newborn being sick at the time of referral-
      Adjusted Odds Ratio (AOR) = 2.3, and 95% Confidence-Interval (CI) of [1.6 -
      3.5]), the CHW making a reminder visit to the referred newborn shortly after
      referral (AOR =1.7; 95% CI: [1.2 -2.7]); and age of mother (25-29) and (30-34)
      years, (AOR =0.4; 95% CI: [0.2 - 0.8]) and (AOR = 0.4; 95% CI: [0.2 - 0.8])
      respectively. CONCLUSION: Caretakers' newborn referral compliance was high in
      this setting. The newborn being sick, being born to a younger mother and a
      reminder visit by the CHW to a referred newborn were predictors of newborn
      referral compliance. Integration of CHWs into maternal and newborn care programs
      has the potential to increase care seeking for newborns, which may contribute to
      reduction of newborn mortality.

PMID- 24312325
TI  - Glycosylphosphatidylinositol-anchored proteins in Fusarium graminearum:
      inventory, variability, and virulence.
AB  - The contribution of cell surface proteins to plant pathogenicity of fungi is not
      well understood. As such, the objective of this study was to investigate the
      functions and importance of glycosylphosphatidylinositol-anchored proteins (GPI
      APs) in the wheat pathogen F. graminearum. GPI-APs are surface proteins that are
      attached to either the membrane or cell wall. In order to simultaneously disrupt
      several GPI-APs, a phosphoethanolamine transferase-encoding gene gpi7 was deleted
      and the resultant mutant characterized in terms of growth, development, and
      virulence. The Deltagpi7 mutants exhibited slower radial growth rates and
      aberrantly shaped macroconidia. Furthermore, virulence tests and microscopic
      analyses indicated that Gpi7 is required for ramification of the fungus
      throughout the rachis of wheat heads. In parallel, bioinformatics tools were
      utilized to predict and inventory GPI-APs within the proteome of F. graminearum.
      Two of the genes identified in this screen (FGSG_01588 and FGSG_08844) displayed
      isolate-specific length variability as observed for other fungal cell wall
      adhesion genes. Nevertheless, deletion of these genes failed to reveal obvious
      defects in growth, development, or virulence. This research demonstrates the
      global importance of GPI-APs to in planta proliferation in F. graminearum, and
      also highlights the potential of individual GPI-APs as diagnostic markers. 

PMID- 24312327
TI  - How can ten fingers shape a pot? Evidence for equivalent function in culturally
      distinct motor skills.
AB  - Behavioural variability is likely to emerge when a particular task is performed
      in different cultural settings, assuming that part of human motor behaviour is
      influenced by culture. In analysing motor behaviour it is useful to distinguish
      how the action is performed from the result achieved. Does cultural environment
      lead to specific cultural motor skills? Are there differences between cultures
      both in the skills themselves and in the corresponding outcomes? Here we analyse
      the skill of pottery wheel-throwing in French and Indian cultural environments.
      Our specific goal was to examine the ability of expert potters from distinct
      cultural settings to reproduce a common model shape (a sphere). The operational
      aspects of motor performance were captured through the analysis of the hand
      positions used by the potters during the fashioning process. In parallel, the
      outcomes were captured by the geometrical characteristics of the vessels
      produced. As expected, results revealed a cultural influence on the operational
      aspects of the potters' motor skill. Yet, the marked cultural differences in hand
      positions used did not give rise to noticeable differences in the shapes of the
      vessels produced. Hence, for the simple model form studied, the culturally
      specific motor traditions of the French and Indian potters gave rise to an
      equivalent outcome, that is shape uniformity. Further work is needed to test
      whether such equivalence is also observed in more complex ceramic shapes. 

PMID- 24312328
TI  - Self-healing efficiency of cementitious materials containing microcapsules filled
      with healing adhesive: mechanical restoration and healing process monitored by
      water absorption.
AB  - Autonomous crack healing of cementitious composite, a construction material that
      is susceptible to cracking, is of great significance to improve the
      serviceability and to prolong the longevity of concrete structures. In this
      study, the St-DVB microcapsules enclosing epoxy resins as the adhesive agent were
      embedded in cement paste to achieve self-healing capability. The self-healing
      efficiency was firstly assessed by mechanical restoration of the damaging
      specimens after being matured. The flexural and compressive configurations were
      both used to stimulate the localized and distributed cracks respectively. The
      effects of some factors, including the content of microcapsules, the curing
      conditions and the degree of damage on the healing efficiency were investigated.
      Water absorption was innovatively proposed to monitor and characterize the
      evolution of crack networks during the healing process. The healing cracks were
      observed by SEM-EDS following. The results demonstrated that the capsule
      containing cement paste can achieve the various mechanical restorations depending
      on the curing condition and the degree of damage. But the voids generated by the
      surfactants compromised the strength. Though no noticeable improved stiffness
      obtained, the increasing fracture energy was seen particularly for the specimen
      acquiring 60% pre-damage. The sorptivity and amount of water decreased with
      cracks healing by the adhesive, which contributed to cut off and block ingress of
      water. The micrographs by SEM-EDS also validated that the cracks were bridged by
      the hardened epoxy as the dominated elements of C and O accounted for 95% by mass
      in the nearby cracks. 

PMID- 24312329
TI  - Serum S100B, lactate dehydrogenase and brain metastasis are prognostic factors in
      patients with distant melanoma metastasis and systemic therapy.
AB  - BACKGROUND: Prognostic factors of melanoma with distant metastasis and systemic
      treatment are only poorly established. This study aimed to analyse the impact of
      S100B, lactate dehydrogenase (LDH) and the type of treatment on survival in
      advanced patients receiving systemic treatment. PATIENTS AND METHODS: We analysed
      overall survival of 499 patients from the university department of dermatology in
      Tuebingen, Germany, with unresectable melanoma at the time point of initiation of
      first-line systemic therapy. Only patients who started treatment between the
      years 2000 and 2010 were included. Disease-specific survival was calculated by
      bivariate Kaplan Meier survival probabilities and multivariate Cox hazard
      regression analysis. RESULTS: In univariate analysis LDH, S100B, the site of
      distant metastasis (soft tissue vs. lung vs. other visceral), the presence of
      brain metastases and the type of treatment (monochemotherapy, polychemotherapy,
      immunotherapy or biochemotherapy) were associated with overall survival (all
      p<0.001). In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3-2.1];
      p<0.001), S100B (HR 1.6 [1.2-2.1]; p<0.001) and the presence of brain metastases
      (HR 1.5 [1.1-1.9]; p = 0.009), but not the type of treatment had significant
      independent impact. Among those factors normal S100B was the best indicator of
      long-term survival, which was 12.3% after 5 years for this subgroup. CONCLUSION:
      Serum S100B is a prognostic marker predicting survival at the time of initiation
      of first-line treatment in unresectable melanoma patients. Compared to the other
      independent factors LDH and the presence of brain metastases it is most
      appropriate to predict long-term survival and requires further prospective
      investigation in patients treated with new and more potent drugs in metastatic
      melanoma.

PMID- 24312330
TI  - Identification and monitoring of host cell proteins by mass spectrometry combined
      with high performance immunochemistry testing.
AB  - Biotherapeutics are often produced in non-human host cells like Escherichia coli,
      yeast, and various mammalian cell lines. A major focus of any therapeutic protein
      purification process is to reduce host cell proteins to an acceptable low level.
      In this study, various E. coli host cell proteins were identified at different
      purifications steps by HPLC fractionation, SDS-PAGE analysis, and tryptic peptide
      mapping combined with online liquid chromatography mass spectrometry (LC-MS).
      However, no host cell proteins could be verified by direct LC-MS analysis of
      final drug substance material. In contrast, the application of affinity
      enrichment chromatography prior to comprehensive LC-MS was adequate to identify
      several low abundant host cell proteins at the final drug substance level.
      Bacterial alkaline phosphatase (BAP) was identified as being the most abundant
      host cell protein at several purification steps. Thus, we firstly established two
      different assays for enzymatic and immunological BAP monitoring using the
      cobas(r) technology. By using this strategy we were able to demonstrate an almost
      complete removal of BAP enzymatic activity by the established therapeutic protein
      purification process. In summary, the impact of fermentation, purification, and
      formulation conditions on host cell protein removal and biological activity can
      be conducted by monitoring process-specific host cell proteins in a GMP
      compatible and high-throughput (> 1000 samples/day) manner. 

PMID- 24312331
TI  - Comparative proteomic analysis reveals the cross-talk between the responses
      induced by H2O2 and by long-term rice black-streaked dwarf virus infection in
      rice.
AB  - Hydrogen peroxide (H2O2) could be produced during the plant-virus compatible
      interaction. However, the cell responses regulated by the enhanced H2O2 in virus
      infected plant are largely unknown. To make clear the influence of Rice black
      streaked dwarf virus (RBSDV) infection on H2O2 accumulation, we measured the
      content of H2O2 and found the H2O2 level was increased in rice seedlings
      inoculated with RBSDV. To reveal the responses initiated by the enhanced H2O2
      during plant-virus interaction, the present study investigated the global
      proteome changes of rice under long-term RBSDV infection. Approximately 1800
      protein spots were detected on two-dimensional electrophoresis (2-DE) gels. Among
      them, 72 spots were found differently expressed, of which 69 spots were
      successfully identified by MALDI-TOF/TOF-MS. Furthermore, the differentially
      expressed proteins induced by RBSDV infection were compared to that induced by
      H2O2. 19 proteins corresponding to 37 spots, which were differentially expressed
      under RBSDV infection, were observed differentially expressed under H2O2 stress
      as well. These overlapping responsive proteins are mainly related to
      photosynthesis, redox homeostasis, metabolism, energy pathway, and cell wall
      modification. The increased H2O2 in RBSDV infected plant may produce an oxidative
      stress, impair photosynthesis, disturb the metabolism, and eventually result in
      abnormal growth. The data provide a new understanding of the pivotal role of H2O2
      in rice-RBSDV compatible interaction. 

PMID- 24312332
TI  - Sensitivity of heterogeneous marine benthic habitats to subtle stressors.
AB  - It is important to understand the consequences of low level disturbances on the
      functioning of ecological communities because of the pervasiveness and frequency
      of this type of environmental change. In this study we investigated the response
      of a heterogeneous, subtidal, soft-sediment habitat to small experimental
      additions of organic matter and calcium carbonate to examine the sensitivity of
      benthic ecosystem functioning to changes in sediment characteristics that relate
      to the environmental threats of coastal eutrophication and ocean acidification.
      Our results documented significant changes between key biogeochemical and
      sedimentary variables such as gross primary production, ammonium uptake and
      dissolved reactive phosphorus flux following treatment additions. Moreover, the
      application of treatments affected relationships between macrofauna communities,
      sediment characteristics (e.g., chlorophyll a content) and biogeochemical
      processes (oxygen and nutrient fluxes). In this experiment organic matter and
      calcium carbonate showed persistent opposing effects on sedimentary processes,
      and we demonstrated that highly heterogeneous sediment habitats can be
      surprisingly sensitive to subtle perturbations. Our results have important
      biological implications in a world with relentless anthropogenic inputs of
      atmospheric CO2 and nutrients in coastal waters. 

PMID- 24312333
TI  - Enhanced reliability and accuracy for field deployable bioforensic detection and
      discrimination of Xylella fastidiosa subsp. pauca, causal agent of citrus
      variegated chlorosis using razor ex technology and TaqMan quantitative PCR.
AB  - A reliable, accurate and rapid multigene-based assay combining real time
      quantitative PCR (qPCR) and a Razor Ex BioDetection System (Razor Ex) was
      validated for detection of Xylella fastidiosa subsp. pauca (Xfp, a xylem-limited
      bacterium that causes citrus variegated chlorosis [CVC]). CVC, which is exotic to
      the United States, has spread through South and Central America and could
      significantly impact U.S. citrus if it arrives. A method for early, accurate and
      sensitive detection of Xfp in plant tissues is needed by plant health officials
      for inspection of products from quarantined locations, and by extension
      specialists for detection, identification and management of disease outbreaks and
      reservoir hosts. Two sets of specific PCR primers and probes, targeting Xfp genes
      for fimbrillin and the periplasmic iron-binding protein were designed. A third
      pair of primers targeting the conserved cobalamin synthesis protein gene was
      designed to detect all possible X. fastidiosa (Xf) strains. All three primer sets
      detected as little as 1 fg of plasmid DNA carrying X. fastidiosa target sequences
      and genomic DNA of Xfp at as little as 1 - 10 fg. The use of Razor Ex facilitates
      a rapid (about 30 min) in-field assay capability for detection of all Xf strains,
      and for specific detection of Xfp. Combined use of three primer sets targeting
      different genes increased the assay accuracy and broadened the range of
      detection. To our knowledge, this is the first report of a field-deployable rapid
      and reliable bioforensic detection and discrimination method for a bacterial
      phytopathogen based on multigene targets. 

PMID- 24312334
TI  - Bone mineral density measurements, bone markers and serum vitamin D
      concentrations in men with chronic non-cirrhotic untreated hepatitis C.
AB  - INTRODUCTION: The high prevalence of chronic hepatitis C (CHC) and its consequent
      cirrhosis has been associated with bone fragility. Whether CHC may cause bone and
      mineral abnormalities in the absence of hepatocellular dysfunction is still
      unknown. In this study we aimed to determine the prevalence of osteoporotic
      vertebral fractures and low BMD measurements in men with non-cirrhotic CHC. Risk
      factors for low BMD and fractures were also investigated. METHODS: Morphometric
      vertebral fractures and BMD measurements were performed in 60 non-cirrhotic
      untreated men with CHC and 59 healthy controls, matched for age and gender,
      weight and current smoking. Serum CTx, calcium, phosphate, intact PTH, alkaline
      phosphatase and vitamin D (25OHD) concentrations were measured in all
      participants. Clinical risk factors for low BMD and fractures were evaluated by a
      structured questionnaire as well as details regarding HCV infection. RESULTS:
      Trochanter and total femur BMD were significantly lower in CHC patients as
      compared to healthy men (p = 0.04). In men 50 years and older, the prevalence of
      osteoporosis was significantly higher among CHC patients (p = 0.01). Lower levels
      of physical activities and more often report of prolonged immobilization were
      observed among CHC patients (p<0.05). Liver inflammation and fibrosis, viral load
      and genotype did not correlate with BMD measurements. Bone markers and 25OHD
      concentrations were similar in both groups. Only a few vertebral fractures were
      observed. CONCLUSIONS: Our results demonstrate that non-cirrhotic untreated CHC
      patients have lower BMD at the femur as compared to healthy men in spite of the
      absence of significant bone and mineral abnormalities.

PMID- 24312335
TI  - Gender and age interact to affect early outcome after intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is a common and devastating form of
      cerebrovascular disease. In ICH, gender differences in outcomes remain relatively
      understudied but have been examined in other neurological emergencies. Further, a
      potential effect of age and gender on outcomes after ICH has not been explored.
      This study was designed to test the hypothesis that age and gender interact to
      modify neurological outcomes after ICH. METHODS: Adult patients admitted with
      spontaneous primary supratentorial ICH from July 2007 through April 2010 were
      assessed via retrospective analysis of an existing stroke database at Duke
      University. Univariate analysis of collected variables was used to compare gender
      and outcome. Unfavorable outcome was defined as discharge to hospice or death.
      Using multivariate regression, the combined effect of age and gender on outcome
      after ICH was analyzed. RESULTS: In this study population, women were younger
      (61.1+14.5 versus 65.8+17.3 years, p=0.03) and more likely to have a history of
      substance abuse (35% versus 8.9%, p<0.0001) compared to men. Multivariable models
      demonstrated that advancing age had a greater effect on predicting discharge
      outcome in women compared to men (p=0.02). For younger patients, female sex was
      protective; however, at ages greater than 60 years, female sex was a risk factor
      for discharge to hospice or death. CONCLUSION: While independently associated
      with discharge to hospice or death after ICH, the interaction effect between
      gender and age demonstrated significantly stronger correlation with early outcome
      after ICH in a single center cohort. Prospective study is required to verify
      these findings.

PMID- 24312336
TI  - Bayesian inference of the evolution of HBV/E.
AB  - Despite its wide spread and high prevalence in sub-Saharan Africa, hepatitis B
      virus genotype E (HBV/E) has a surprisingly low genetic diversity, indicating an
      only recent emergence of this genotype in the general African population. Here,
      we performed extensive phylogeographic analyses, including Bayesian MCMC
      modeling. Our results indicate a mutation rate of 1.9 * 10(-4) substitutions per
      site and year (s/s/y) and confirm a recent emergence of HBV/E, most likely within
      the last 130 years, and only after the transatlantic slave-trade had come to an
      end. Our analyses suggest that HBV/E originated from the area of Nigeria, before
      rapidly spreading throughout sub-Saharan Africa. Interestingly, viral strains
      found in Haiti seem to be the result of multiple introductions only in the second
      half of the 20th century, corroborating an absence of a significant number of
      HBV/E strains in West Africa several centuries ago. Our results confirm that the
      hyperendemicity of HBV(E) in today's Africa is a recent phenomenon and likely the
      result of dramatic changes in the routes of viral transmission in a relatively
      recent past.

PMID- 24312337
TI  - Pathway and mechanism of pH dependent human hemoglobin tetramer-dimer-monomer
      dissociations.
AB  - Hemoglobin dissociation is of great interest in protein process and clinical
      medicine as well as in artificial blood research. However, the pathway and
      mechanisms of pH-dependent human Hb dissociation are not clear, whether Hb would
      really dissociate into monomers is still a question. Therefore, we have conducted
      a multi-technique investigation on the structure and function of human Hb versus
      pH. Here we demonstrate that tetramer hemoglobin can easily dissociate into dimer
      in abnormal pH and the tetramer -> dimer dissociation is reversible if pH returns
      to normal physiological value. When the environmental pH becomes more acidic
      (<6.5) or alkaline (>8.0), Hb can further dissociate from dimer to monomer. The
      proportion of monomers increases while the fraction of dimers decreases as pH
      declines from 6.2 to 5.4. The dimer -> monomer dissociation is accompanied with
      series changes of protein structure thus it is an irreversible process. The
      structural changes in the dissociated Hbs result in some loss of their functions.
      Both the Hb dimer and monomer cannot adequately carry and release oxygen to the
      tissues in circulation. These findings provide a comprehensive understanding on
      the pH-dependent protein transitions of human Hb, give guideline to explain
      complex protein processes and the means to control protein dissociation or re
      association reaction. They are also of practical value in clinical medicine,
      blood preservation and blood substitute development.

PMID- 24312338
TI  - RhoE promotes metastasis in gastric cancer through a mechanism dependent on
      enhanced expression of CXCR4.
AB  - RhoE, a novel member of the Rho protein family, is a key regulator of the
      cytoskeleton and cell migration. Our group has previously shown that RhoE as a
      direct target for HIF-1alpha and mediates hypoxia-induced epithelial to
      mesenchymal transition in gastric cancer cells. Therefore, we assumed that RhoE
      might play an important role in gastric cancer metastasis. In the present study,
      we have explored the role of RhoE expression in gastric cancer, cell invasion and
      metastasis, and the influence of RhoE on regulating the potential expression of
      down-stream genes. RhoE expression was elevated in gastric cancer tissues as
      compared with normal gastric tissues. We also found a close correlation between
      the histological grade and the diagnosis of the patient. Up-regulation of RhoE
      significantly enhanced the migratory and invasive abilities of gastric cancer
      cells both in vitro and in vivo. Moreover, down-regulation of RhoE diminished the
      metastatic potential of cancer cells. PCR array and subsequent transwell assay
      showed that the regulation of gastric cancer metastasis by RhoE was partially
      mediated by CXCR4. This observation suggested that CXCR4 might be a downstream
      effector for RhoE. In summary, our study identified RhoE as a novel prognostic
      biomarker and metastatic-promoting gene of gastric cancer. 

PMID- 24312341
TI  - The value of emotion: how does episodic prospection modulate delay discounting?
AB  - BACKGROUND: Humans often show impatience when making intertemporal choice for
      monetary rewards, preferring small rewards delivered immediately to larger
      rewards delivered after a delay, which reflects a fundamental psychological
      principle: delay discounting. However, we propose that episodic prospection
      humans can vividly envisage exerts a strong and broad influence on individuals'
      delay discounting. Specifically, episodic prospection may affect individuals'
      intertemporal choice by the negative or positive emotion of prospection.
      METHODOLOGY/PRINCIPAL FINDINGS: The present study explored how episodic
      prospection modulated delay discounting by emotion. Study 1 showed that
      participants were more inclined to choose the delayed but larger rewards when
      they imaged positive future events than when they did not image events; Study 2
      showed that participants were more inclined to choose the immediate but smaller
      rewards when they imaged negative future events than when they did not image
      events; In contrast, study 3 showed that choice preferences of participants when
      they imaged neutral future events were the same as when they did not image
      events. CONCLUSIONS/SIGNIFICANCE: By manipulating the emotion valence of episodic
      prospection, our findings suggested that positive emotion made individuals tend
      to choose delayed rewards, while negative emotion made individuals tend to choose
      immediate rewards. Only imaging events with neutral emotion did not affect
      individuals' choice preference. Thus, the valence of imaged future events'
      emotion might play an important role in individuals' intertemporal choice. It is
      possible that the valence of emotion may affect the changed direction (promote or
      inhibit) of individuals' delay discounting, while the ability to image future
      events affects the changed degree of individuals' delay discounting.

PMID- 24312340
TI  - RGMa regulates cortical interneuron migration and differentiation.
AB  - The etiology of neuropsychiatric disorders, including schizophrenia and autism,
      has been linked to a failure to establish the intricate neural network comprising
      excitatory pyramidal and inhibitory interneurons during neocortex development. A
      large proportion of cortical inhibitory interneurons originate in the medial
      ganglionic eminence (MGE) of the ventral telencephalon and then migrate through
      the ventral subventricular zone, across the corticostriatal junction, into the
      embryonic cortex. Successful navigation of newborn interneurons through the
      complex environment of the ventral telencephalon is governed by spatiotemporally
      restricted deployment of both chemorepulsive and chemoattractive guidance cues
      which work in concert to create a migratory corridor. Despite the expanding list
      of interneuron guidance cues, cues responsible for preventing interneurons from
      re-entering the ventricular zone of the ganglionic eminences have not been well
      characterized. Here we provide evidence that the chemorepulsive axon guidance
      cue, RGMa (Repulsive Guidance Molecule a), may fulfill this function. The
      ventricular zone restricted expression of RGMa in the ganglionic eminences and
      the presence of its receptor, Neogenin, in the ventricular zone and on newborn
      and maturing MGE-derived interneurons implicates RGMa-Neogenin interactions in
      interneuron differentiation and migration. Using an in vitro approach, we show
      that RGMa promotes interneuron differentiation by potentiating neurite outgrowth.
      In addition, using in vitro explant and migration assays, we provide evidence
      that RGMa is a repulsive guidance cue for newborn interneurons migrating out of
      the ganglionic eminence ventricular zone. Intriguingly, the alternative Neogenin
      ligand, Netrin-1, had no effect on migration. However, we observed complete
      abrogation of RGMa-induced chemorepulsion when newborn interneurons were
      simultaneously exposed to RGMa and Netrin-1 gradients, suggesting a novel
      mechanism for the tight regulation of RGMa-guided interneuron migration. We
      propose that during peak neurogenesis, repulsive RGMa-Neogenin interactions drive
      interneurons into the migratory corridor and prevent re-entry into the
      ventricular zone of the ganglionic eminences. 

PMID- 24312339
TI  - Mutational analysis of sclerostin shows importance of the flexible loop and the
      cystine-knot for Wnt-signaling inhibition.
AB  - The cystine-knot containing protein Sclerostin is an important negative regulator
      of bone growth and therefore represents a promising therapeutic target. It exerts
      its biological task by inhibiting the Wnt (wingless and int1) signaling pathway,
      which participates in bone formation by promoting the differentiation of
      mesenchymal stem cells to osteoblasts. The core structure of Sclerostin consists
      of three loops with the first and third loop (Finger 1 and Finger 2) forming a
      structured beta-sheet and the second loop being unstructured and highly flexible.
      Biochemical data showed that the flexible loop is important for binding of
      Sclerostin to Wnt co-receptors of the low-density lipoprotein related-protein
      family (LRP), by interacting with the Wnt co-receptors LRP5 or -6 it inhibits Wnt
      signaling. To further examine the structural requirements for Wnt inhibition, we
      performed an extensive mutational study within all three loops of the Sclerostin
      core domain involving single and multiple mutations as well as truncation of
      important regions. By this approach we could confirm the importance of the second
      loop and especially of amino acids Asn92 and Ile94 for binding to LRP6. Based on
      a Sclerostin variant found in a Turkish family suffering from Sclerosteosis we
      generated a Sclerostin mutant with cysteines 84 and 142 exchanged thereby
      removing the third disulfide bond of the cystine-knot. This mutant binds to LRP6
      with reduced binding affinity and also exhibits a strongly reduced inhibitory
      activity against Wnt1 thereby showing that also elements outside the flexible
      loop are important for inhibition of Wnt by Sclerostin. Additionally, we examined
      the effect of the mutations on the inhibition of two different Wnt proteins,
      Wnt3a and Wnt1. We could detect clear differences in the inhibition of these
      proteins, suggesting that the mechanism by which Sclerostin antagonizes Wnt1 and
      Wnt3a is fundamentally different. 

PMID- 24312342
TI  - Characterization of CD56+ dendritic-like cells: a normal counterpart of blastic
      plasmacytoid dendritic cell neoplasm?
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological
      malignancy. Plasmacytoid DCs (pDCs), which are defined as lineage marker (Lin)(
      )HLA-DR(+)CD56(-)CD123(+)CD11c(-) cells, are considered to be the normal
      counterpart of BPDCNs. However, BPDCN can be distinguished from pDCs by uniform
      expression of CD56. In this study, to identify a normal counterpart of BPDCN, we
      searched for a Lin(-)HLA-DR(+)CD56(+) population and focused on a minor
      subpopulation of Lin(-)DR(+)CD56(+)CD123(+)CD11c(-) cells that we designated as
      pDC-like cells (pDLCs). pDLC constituted 0.03% of peripheral blood mononuclear
      cells (PBMCs), and the pDLC/pDC ratio was higher in bone marrow cells than in
      PBMCs. pDLC clearly expressed BDCA2, BDCA4, and myeloid antigens, which are
      frequently expressed by BPDCN. pDLCs exhibited modest expression of Toll-like
      receptors and produced less interferon-alpha after CpG stimulation, but presented
      very low endocytic ability unlike mDCs. These functional differences were
      attributed to the expression profile of transcriptional factors. After in vitro
      culture with Flt3-ligand and GM-CSF, pDLCs expressed CD11c and BDCA1. These data
      suggested that pDLCs are a distinct subpopulation, with an immunophenotype
      similar to BPDCNs. Moreover, our results indicate that pDLCs might be immature
      DCs and might contribute to the immunophenotypical diversity of BPDCNs. 

PMID- 24312344
TI  - Singing-related activity in anterior forebrain of male zebra finches reflects
      courtship motivation for target females.
AB  - A critical function of singing by male songbirds is to attract a female mate.
      Previous studies have suggested that the anterior forebrain system is involved in
      this courtship behavior. Neural activity in this system, including the striatal
      Area X, is strikingly dependent on the function of male singing. When males sing
      to attract a female bird rather than while alone, less variable neural activity
      results in less variable song spectral features, which may be attractive to the
      female. These characteristics of neural activity and singing thus may reflect a
      male's motivation for courtship. Here, we compared the variability of neural
      activity and song features between courtship singing directed to a female with
      whom a male had previously formed a pair-bond or to other females. Surprisingly,
      across all units, there was no clear tendency for a difference in variability of
      neural activity or song features between courtship of paired females, nonpaired
      females, or dummy females. However, across the population of recordings, there
      was a significant relationship between the relative variability of syllable
      frequency and neural activity: when syllable frequency was less variable to
      paired than nonpaired females, neural activity was also less variable (and vice
      versa). These results show that the lower variability of neural activity and
      syllable frequency during directed singing is not a binary distinction from
      undirected singing, but can vary in intensity, possibly related to the relative
      preference of a male for his singing target. 

PMID- 24312343
TI  - Extracts of Rhizoma polygonati odorati prevent high-fat diet-induced metabolic
      disorders in C57BL/6 mice.
AB  - Polygonatum odoratum (Mill.) Druce belongs to the genus Polygonatum family of
      plants. In traditional Chinese medicine, the root of Polygonatum odoratum,
      Rhizoma Polygonati Odorati, is used both for food and medicine to prevent and
      treat metabolic disorders such as hyperlipidemia, hyperglycemia, obesity and
      cardiovascular disease. However, there is no solid experimental evidence to
      support these applications, and the underlying mechanism is also needed to be
      elucidated. Here, we examined the effect of the extract of Rhizoma Polygonati
      Odorati (ER) on metabolic disorders in diet-induced C57BL/6 obese mice. In the
      preventive experiment, the ER blocked body weight gain, and lowered serum total
      cholesterol (TC), triglyceride (TG) and fasting blood glucose, improved glucose
      tolerance test (GTT) and insulin tolerance test (ITT), reduced the levels of
      serum insulin and leptin, and increased serum adiponectin levels in mice fed with
      a high-fat diet significantly. In the therapeutic study, we induced obesity in
      the mice and treated the obese mice with ER for two weeks. We found that ER
      treatments reduced serum TG and fasting blood glucose, and improved glucose
      tolerance in the mice. Gene expression analysis showed that ER increased the mRNA
      levels of peroxisome proliferator-activated receptors (PPAR) gamma and alpha and
      their downstream target genes in mice livers, adipose tissues and HepG2 cells.
      Our data suggest that ER ameliorates metabolic disorders and enhances the mRNA
      expression of PPARs in obese C57BL/6 mice induced by high-fat diet. 

PMID- 24312345
TI  - Protease activated receptor-2 contributes to heart failure.
AB  - Heart failure is a major clinical problem worldwide. Previous studies have
      demonstrated an important role for G protein-coupled receptors, including
      protease-activated receptors (PARs), in the pathology of heart hypertrophy and
      failure. Activation of PAR-2 on cardiomyocytes has been shown to induce
      hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and
      heart remodeling after ischemia/reperfusion injury. In this study, we found that
      PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a
      MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse
      cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1.
      Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart
      hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a
      mouse model of myocardial infarction induced by permanent ligation of the left
      anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling
      and improved heart function independently of its contribution to the size of the
      initial infarct. Taken together, our data indicate that PAR-2 signaling
      contributes to the pathogenesis of hypertrophy and heart failure. 

PMID- 24312347
TI  - Functional and phylogenetic relatedness in temporary wetland invertebrates:
      current macroecological patterns and implications for future climatic change
      scenarios.
AB  - In freshwater ecosystems, species compositions are known to be determined
      hierarchically by large to small-scale environmental factors, based on the
      biological traits of the organisms. However, in ephemeral habitats this heuristic
      framework remains largely untested. Although temporary wetland faunas are
      constrained by a local filter (i.e., desiccation), we propose its magnitude may
      still depend on large-scale climate characteristics. If this is true, climate
      should be related to the degree of functional and taxonomic relatedness of
      invertebrate communities inhabiting seasonal wetlands. We tested this hypothesis
      in two ways. First, based on 52 biological traits for invertebrates, we conducted
      a case study to explore functional trends among temperate seasonal wetlands
      differing in the harshness (i.e., dryness) of their dry season. After finding
      evidence of trait filtering, we addressed whether it could be generalized across
      a broader climatic scale. To this end, a meta-analysis (225 seasonal wetlands
      spread across broad climatic categories: Arid, Temperate, and Cold) allowed us to
      identify whether an equivalent climate-dependent pattern of trait richness was
      consistent between the Nearctic and the Western Palearctic. Functional overlap of
      invertebrates increased from mild (i.e., Temperate) to harsher climates (i.e.,
      Arid and Cold), and phylogenetic clustering (using taxonomy as a surrogate) was
      highest in Arid and lowest in Temperate wetlands. We show that, (i) as has been
      described in streams, higher relatedness than would be expected by chance is
      generally observed in seasonal wetland invertebrate communities; and (ii) this
      relatedness is not constant but climate-dependent, with the climate under which a
      given seasonal wetland is located determining the functional overlap and the
      phylogenetic clustering of the community. Finally, using a space-for-time
      substitution approach we suggest our results may anticipate how the invertebrate
      biodiversity embedded in these vulnerable and often overlooked ecosystems will be
      affected by long-term climate change. 

PMID- 24312346
TI  - Tumor necrosis factor B (TNFB) genetic variants and its increased expression are
      associated with vitiligo susceptibility.
AB  - Genetic polymorphisms in TNFB are involved in the regulation of its expression
      and are found to be associated with various autoimmune diseases. The aim of the
      present study was to determine whether TNFB +252A/G (rs909253) and exon 3 C/A
      (rs1041981) polymorphisms are associated with vitiligo susceptibility, and
      expression of TNFB and ICAM1 affects the disease onset and progression. We have
      earlier reported the role of TNFA in autoimmune pathogenesis of vitiligo, and we
      now show the involvement of TNFB in vitiligo pathogenesis. The two polymorphisms
      investigated in the TNFB were in strong linkage disequilibrium and significantly
      associated with vitiligo. TNFB and ICAM1 transcripts were significantly increased
      in patients compared to controls. Active vitiligo patients showed significant
      increase in TNFB transcripts compared to stable vitiligo. The genotype-phenotype
      analysis revealed that TNFB expression levels were higher in patients with GG and
      AA genotypes as compared to controls. Patients with the early age of onset and
      female patients showed higher TNFB and ICAM1 expression. Overall, our findings
      suggest that the increased TNFB transcript levels in vitiligo patients could
      result, at least in part, from variations at the genetic level which in turn
      leads to increased ICAM1 expression. For the first time, we show that TNFB
      +252A/G and exon 3 C/A polymorphisms are associated with vitiligo susceptibility
      and influence the TNFB and ICAM1 expression. Moreover, the study also emphasizes
      influence of TNFB and ICAM1 on the disease progression, onset and gender bias for
      developing vitiligo. 

PMID- 24312348
TI  - Clinical implications of the cervical Papanicolaou test results in the management
      of anal warts in HIV-infected women.
AB  - The Papanicolaou test (or Pap test) has long been used as a screening tool to
      detect cervical precancerous/cancerous lesions. However, studies on the use of
      this test to predict both the presence and change in size of genital warts are
      limited. We examined whether cervical Papanicolaou test results are associated
      with the size of the largest anal wart over time in HIV-infected women in an on
      going cohort study in the US. A sample of 976 HIV-infected women included in a
      public dataset obtained from the Women's Interagency HIV Study (WIHS) was
      selected for analysis. A linear mixed model was performed to determine the
      relationship between the size of anal warts and cervical Pap test results. About
      32% of participants had abnormal cervical Pap test results at baseline. In the
      adjusted model, a woman with a result of Atypia Squamous Cell Undetermined
      Significance/Low-grade Squamous Intraepithelial Lesion (ASCUS/LSIL) had an anal
      wart, on average, 12.81 mm(2) larger than a woman with normal cervical cytology.
      The growth rate of the largest anal wart after each visit in a woman with
      ASCUS/LSIL was 1.56 mm(2) slower than that of a woman with normal cervical
      results. However, they were not significant (P = 0.54 and P = 0.82,
      respectively). This is the first study to examine the relationship between
      cervical Pap test results and anal wart development in HIV-infected women. Even
      though no association between the size of anal wart and cervical Pap test results
      was found, a screening program using anal cytology testing in HIV-infected women
      should be considered. Further studies in cost-effectiveness and efficacy of an
      anal cytology test screening program are warranted. 

PMID- 24312351
TI  - Glycerol-3-phosphate metabolism in wheat contributes to systemic acquired
      resistance against Puccinia striiformis f. sp. tritici.
AB  - Glycerol-3-phosphate (G3P) is a proposed regulator of plant defense signaling in
      basal resistance and systemic acquired resistance (SAR). The GLY1-encoded
      glycerol-3-phosphate dehydrogenase (G3PDH) and GLI1-encoded glycerol kinase (GK)
      are two key enzymes involved in the G3P biosynthesis in plants. However, their
      physiological importance in wheat defense against pathogens remains unclear. In
      this study, quantification analysis revealed that G3P levels were significantly
      induced in wheat leaves challenged by the avirulent Puccinia striiformis f. sp.
      tritici (Pst) race CYR23. The transcriptional levels of TaGLY1 and TaGLI1 were
      likewise significantly induced by avirulent Pst infection. Furthermore, knocking
      down TaGLY1 and TaGLI1 individually or simultaneously with barley stripe mosaic
      virus-induced gene silencing (BSMV-VIGS) inhibited G3P accumulation and
      compromised the resistance in the wheat cultivar Suwon 11, whereas the
      accumulation of salicylic acid (SA) and the expression of the SA-induced marker
      gene TaPR1 in plant leaves were altered significantly after gene silencing. These
      results suggested that G3P contributes to wheat systemic acquired resistance
      (SAR) against stripe rust, and provided evidence that the G3P function as a
      signaling molecule is conserved in dicots and monocots. Meanwhile, the
      simultaneous co-silencing of multiple genes by the VIGS system proved to be a
      powerful tool for multi-gene functional analysis in plants. 

PMID- 24312349
TI  - Experimental sepsis impairs humoral memory in mice.
AB  - Patients with sepsis are often immune suppressed, and experimental mouse models
      of sepsis also display this feature. However, acute sepsis in mice is also
      characterized by a generalized B cell activation and plasma cell differentiation,
      resulting in a marked increase in serum antibody concentration. Its effects on
      humoral memory are not clearly defined. We measured the effects of experimental
      sepsis on long-term immunological memory for a defined antigen: we induced colon
      ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with
      ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count
      had doubled in immunized non-septic animals, but remained unchanged in immunized
      septic animals. Sepsis also caused a decrease in antigen-specific serum antibody
      concentration. We conclude that sepsis weakens humoral memory by impeding the
      antigen-specific plasma cell pool's development, which is not complete 8 weeks
      after secondary immunization. 

PMID- 24312350
TI  - Heterologous expression of mycobacterial Esx complexes in Escherichia coli for
      structural studies is facilitated by the use of maltose binding protein fusions.
AB  - The expression of heteroligomeric protein complexes for structural studies often
      requires a special coexpression strategy. The reason is that the solubility and
      proper folding of each subunit of the complex requires physical association with
      other subunits of the complex. The genomes of pathogenic mycobacteria encode many
      small protein complexes, implicated in bacterial fitness and pathogenicity, whose
      characterization may be further complicated by insolubility upon expression in
      Escherichia coli, the most common heterologous protein expression host. As
      protein fusions have been shown to dramatically affect the solubility of the
      proteins to which they are fused, we evaluated the ability of maltose binding
      protein fusions to produce mycobacterial Esx protein complexes. A single plasmid
      expression strategy using an N-terminal maltose binding protein fusion to the CFP
      10 homolog proved effective in producing soluble Esx protein complexes, as
      determined by a small-scale expression and affinity purification screen, and
      coupled with intracellular proteolytic cleavage of the maltose binding protein
      moiety produced protein complexes of sufficient purity for structural studies. In
      comparison, the expression of complexes with hexahistidine affinity tags alone on
      the CFP-10 subunits failed to express in amounts sufficient for biochemical
      characterization. Using this strategy, six mycobacterial Esx complexes were
      expressed, purified to homogeneity, and subjected to crystallization screening
      and the crystal structures of the Mycobacterium abscessus EsxEF, M. smegmatis
      EsxGH, and M. tuberculosis EsxOP complexes were determined. Maltose binding
      protein fusions are thus an effective method for production of Esx complexes and
      this strategy may be applicable for production of other protein complexes. 

PMID- 24312352
TI  - Regulatory roles of the PI3K/Akt signaling pathway in rats with severe acute
      pancreatitis.
AB  - The phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) pathway plays a
      key role in inflammation. However, the regulatory roles of PI3K/Akt in severe
      acute pancreatitis (SAP) have not been elucidated. The aim of this study was to
      investigate the impact of wortmannin, a PI3K/Akt inhibitor, on SAP rats through
      exposure to sodium taurocholate (STC) after 3 h and 6 h. The SAP group was found
      to have a significant increase in pancreas Akt expression, along with the
      activation of serum amylase, TNF-alpha, IL-1beta, and IL-6, and pancreas
      histological aggravation. The administration of wortmannin in SAP rats reduced
      Akt expression, attenuated the level of serum amylase and inflammation factor,
      and alleviated the damage of pancreatic tissue. Furthermore, the administration
      of wortmannin led to an obvious reduction in NF-kappaB and p38MAPK expression in
      SAP rats. These findings showed that the PI3K/Akt inhibitor wortmannin decreases
      inflammatory cytokines in SAP rats and suggests its regulatory mechanisms may
      occur through the suppression on NF-kappaB and p38MAPK activity. 

PMID- 24312353
TI  - Production of bioactive soluble interleukin-15 in complex with interleukin-15
      receptor alpha from a conditionally-replicating oncolytic HSV-1.
AB  - Oncolytic type-1 herpes simplex viruses (oHSVs) lacking the gamma134.5
      neurovirulence gene are being evaluated for treatment of a variety of
      malignancies. oHSVs replicate within and directly kill permissive cancer cells.
      To augment their anti-tumor activity, oHSVs have been engineered to express
      immunostimulatory molecules, including cytokines, to elicit tumor-specific immune
      responses. Interleukin-15 (IL-15) holds potential as an immunotherapeutic
      cytokine because it has been demonstrated to promote both natural killer (NK)
      cell-mediated and CD8(+) T cell-mediated cytotoxicity against cancer cells. The
      purpose of these studies was to engineer an oHSV producing bioactive IL-15. Two
      oHSVs were constructed encoding murine (m)IL-15 alone (J100) or with the mIL-15
      receptor alpha (mIL-15Ralpha, J100D) to determine whether co-expression of these
      proteins is required for production of bioactive mIL-15 from oHSV. The following
      were demonstrated: i) both oHSVs retain replication competence and cytotoxicity
      in permissive tumor cell lines. ii) Enhanced production of mIL-15 was detected in
      cell lysates of neuro-2a cells following J100D infection as compared to J100
      infection, suggesting that mIL-15Ralpha improved mIL-15 production. iii) Soluble
      mIL-15 in complex with mIL-15Ralpha was detected in supernates from J100D
      infected, but not J100-infected, neuro-2a, GL261, and CT-2A cells. These cell
      lines vary in permissiveness to oHSV replication and cytotoxicity, demonstrating
      soluble mIL-15/IL-15Ralpha complex production from J100D was independent of
      direct oHSV effects. iv) The soluble mIL-15/IL-15Ralpha complex produced by J100D
      was bioactive, stimulating NK cells to proliferate and reduce the viability of
      syngeneic GL261 and CT-2A cells. v) J100 and J100D were aneurovirulent inasmuch
      as no neuropathologic effects were documented following direct inoculation into
      brains of CBA/J mice at up to 1x10(7) plaque forming units. The production of mIL
      15/mIL-15Ralpha from multiple tumor lines, as well as the lack of neurovirulence,
      renders J100D suitable for investigating the combined effects of oHSV and mIL
      15/IL-15Ralpha in various cancer models. 

PMID- 24312354
TI  - A Caenorhabditis elegans locomotion phenotype caused by transgenic repeats of the
      hlh-17 promoter sequence.
AB  - Transgene technology is one of the most heavily relied upon tools in modern
      biological research. Expression of an exogenous gene within cells, for research
      and therapeutic applications, nearly always includes promoters and other
      regulatory sequences. We found that repeats of a non-protein coding transgenic
      sequence produced profound changes to the behavior of the nematode Caenorhabditis
      elegans. These changes were produced by a glial promoter sequence but,
      unexpectedly, major deficits were observed specifically in backward locomotion, a
      neuron-driven behavior. We also present evidence that this behavioral phenotype
      is transpromoter copy number-dependent and manifests early in development and is
      maintained into adulthood of the worm. 

PMID- 24312355
TI  - Inhibition of protein kinase C delta attenuates allergic airway inflammation
      through suppression of PI3K/Akt/mTOR/HIF-1 alpha/VEGF pathway.
AB  - Vascular endothelial growth factor (VEGF) is supposed to contribute to the
      pathogenesis of allergic airway disease. VEGF expression is regulated by a
      variety of stimuli such as nitric oxide, growth factors, and hypoxia-inducible
      factor-1 alpha (HIF-1alpha). Recently, inhibition of the mammalian target of
      rapamycin (mTOR) has been shown to alleviate cardinal asthmatic features,
      including airway hyperresponsiveness, eosinophilic inflammation, and increased
      vascular permeability in asthma models. Based on these observations, we have
      investigated whether mTOR is associated with HIF-1alpha-mediated VEGF expression
      in allergic asthma. In studies with the mTOR inhibitor rapamycin, we have
      elucidated the stimulatory role of a mTOR-HIF-1alpha-VEGF axis in allergic
      response. Next, the mechanisms by which mTOR is activated to modulate this
      response have been evaluated. mTOR is known to be regulated by phosphoinositide 3
      kinase (PI3K)/Akt or protein kinase C-delta (PKC delta) in various cell types.
      Consistent with these, our results have revealed that suppression of PKC delta by
      rottlerin leads to the inhibition of PI3K/Akt activity and the subsequent
      blockade of a mTOR-HIF-1alpha-VEGF module, thereby attenuating typical asthmatic
      attack in a murine model. Thus, the present data indicate that PKC delta is
      necessary for the modulation of the PI3K/Akt/mTOR signaling cascade, resulting in
      a tight regulation of HIF-1alpha activity and VEGF expression. In conclusion, PKC
      delta may represent a valuable target for innovative therapeutic treatment of
      allergic airway disease. 

PMID- 24312356
TI  - Trichostatin A stabilizes the expression of pluripotent genes in human
      mesenchymal stem cells during ex vivo expansion.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have been considered as ideal cells for
      the treatment of a variety of diseases. However, aging and spontaneous
      differentiation of MSCs during culture expansion dampen their effectiveness.
      Previous studies suggest that ex vivo aging of MSCs is largely caused by
      epigenetic changes particularly a decline of histone H3 acetylation levels in
      promoter regions of pluripotent genes due to inappropriate growth environment.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined whether histone
      deacetylase inhibitor trichostatin A (TSA) could suppress the histone H3
      deacetylation thus maintaining the primitive property of MSCs. We found that in
      regular adherent culture, human MSCs became flatter and larger upon successive
      passaging, while the expression of pluripotent genes such as Oct4, Sox2, Nanog,
      Rex-1, CD133 and TERT decreased markedly. Administration of low concentrations of
      TSA in culture significantly suppressed the morphological changes in MSCs
      otherwise occurred during culture expansion, increased their proliferation while
      retaining their cell contact growth inhibition property and multipotent
      differentiation ability. Moreover, TSA stabilized the expression of the above
      pluripotent genes and histone H3 acetylation levels in K9 and K14 in promoter
      regions of Oct4, Sox2 and TERT. CONCLUSIONS/SIGNIFICANCE: Our results suggest
      that TSA may serve as an effective culture additive to maintain the primitive
      feature of MSCs during culture expansion.

PMID- 24312357
TI  - In the absence of effector proteins, the Pseudomonas aeruginosa type three
      secretion system needle tip complex contributes to lung injury and systemic
      inflammatory responses.
AB  - Herein we describe a pathogenic role for the Pseudomonas aeruginosa type three
      secretion system (T3SS) needle tip complex protein, PcrV, in causing lung
      endothelial injury. We first established a model in which P. aeruginosa wild type
      strain PA103 caused pneumonia-induced sepsis and distal organ dysfunction.
      Interestingly, a PA103 derivative strain lacking its two known secreted
      effectors, ExoU and ExoT [denoted PA103 (DeltaU/DeltaT)], also caused sepsis and
      modest distal organ injury whereas an isogenic PA103 strain lacking the T3SS
      needle tip complex assembly protein [denoted PA103 (DeltaPcrV)] did not. PA103
      (DeltaU/DeltaT) infection caused neutrophil influx into the lung parenchyma, lung
      endothelial injury, and distal organ injury (reminiscent of sepsis). In contrast,
      PA103 (DeltaPcrV) infection caused nominal neutrophil infiltration and lung
      endothelial injury, but no distal organ injury. We further examined pathogenic
      mechanisms of the T3SS needle tip complex using cultured rat pulmonary
      microvascular endothelial cells (PMVECs) and revealed a two-phase, temporal
      nature of infection. At 5-hours post-inoculation (early phase infection), PA103
      (DeltaU/DeltaT) elicited PMVEC barrier disruption via perturbation of the actin
      cytoskeleton and did so in a cell death-independent manner. Conversely, PA103
      (DeltaPcrV) infection did not elicit early phase PMVEC barrier disruption. At 24
      hours post-inoculation (late phase infection), PA103 (DeltaU/DeltaT) induced
      PMVEC damage and death that displayed an apoptotic component. Although PA103
      (DeltaPcrV) infection induced late phase PMVEC damage and death, it did so to an
      attenuated extent. The PA103 (DeltaU/DeltaT) and PA103 (DeltaPcrV) mutants grew
      at similar rates and were able to adhere equally to PMVECs post-inoculation
      indicating that the observed differences in damage and barrier disruption are
      likely attributable to T3SS needle tip complex-mediated pathogenic differences
      post host cell attachment. Together, these infection data suggest that the T3SS
      needle tip complex and/or another undefined secreted effector(s) are important
      determinants of P. aeruginosa pneumonia-induced lung endothelial barrier
      disruption. 

PMID- 24312358
TI  - Motivations for undertaking DNA sequencing-based non-invasive prenatal testing
      for fetal aneuploidy: a qualitative study with early adopter patients in Hong
      Kong.
AB  - BACKGROUND: A newly introduced cell-free fetal DNA sequencing based non-invasive
      prenatal testing (DNA-NIPT) detects Down syndrome with sensitivity of 99% at
      early gestational stage without risk of miscarriage. Attention has been given to
      its public health implications; little is known from consumer perspectives. This
      qualitative study aimed to explore women's motivations for using, and perceptions
      of, DNA-NIPT in Hong Kong. METHODS AND FINDINGS: In-depth interviews were
      conducted with 45 women who had undertaken DNA-NIPT recruited by purposive
      sampling based on socio-demographic and clinical characteristics. The sample
      included 31 women identified as high-risk from serum and ultrasound based Down
      syndrome screening (SU-DSS). Thematic narrative analysis examined informed
      decision making of the test and identified the benefits and needs. Women outlined
      a number of reasons for accessing DNA-NIPT: reducing the uncertainty associated
      with risk probability-based results from SU-DSS, undertaking DNA-NIPT as a
      comprehensive measure to counteract risk from childbearing especially at advanced
      age, perceived predictive accuracy and absence of risk of harm to fetus. Accounts
      of women deemed high-risk or not high-risk are distinctive in a number of
      respects. High-risk women accessed DNA-NIPT to get a clearer idea of their risk.
      This group perceived SU-DSS as an unnecessary and confusing procedure because of
      its varying, protocol-dependent detection rates. Those women not deemed high
      risk, in contrast, undertook DNA-NIPT for psychological assurance and to reduce
      anxiety even after receiving the negative result from SU-DSS. CONCLUSIONS: DNA
      NIPT was regarded positively by women who chose this method of screening over the
      routine, less expensive testing options. Given its perceived utility, health
      providers need to consider whether DNA-NIPT should be offered as part of
      universal routine care to women at high-risk for fetal aneuploidy. If this is the
      case, then further development of guidelines and quality assurance will be needed
      to provide a service suited to patients' needs.

PMID- 24312359
TI  - Obesity is associated with lower coronary microvascular density.
AB  - BACKGROUND: Obesity is associated with diastolic dysfunction, lower maximal
      myocardial blood flow, impaired myocardial metabolism and increased risk of heart
      failure. We examined the association between obesity, left ventricular filling
      pressure and myocardial structure. METHODS: We performed histological analysis of
      non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing
      coronary artery bypass graft surgery who did not have previous cardiac surgery,
      myocardial infarction, heart failure, atrial fibrillation or loop diuretic
      therapy. RESULTS: Non-obese (body mass index, BMI, <= 30 kg/m(2), n=33) and obese
      patients (BMI >30 kg/m(2), n=24) did not differ with respect to myocardial total,
      interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte
      width. Obese patients had lower capillary length density (1145 +/- 239, mean +/-
      SD, vs. 1371 +/- 333 mm/mm(3), P=0.007) and higher diffusion radius (16.9 +/- 1.5
      vs. 15.6 +/- 2.0 MUm, P=0.012), in comparison with non-obese patients. However,
      the diffusion radius/cardiomyocyte width ratio of obese patients (0.73 +/- 0.11
      MUm/MUm) was not significantly different from that of non-obese patients (0.71 +/
      0.11 MUm/MUm), suggesting that differences in cardiomyocyte width explained in
      part the differences in capillary length density and diffusion radius between non
      obese and obese patients. Increased BMI was associated with increased pulmonary
      capillary wedge pressure (PCWP, P<0.0001), and lower capillary length density was
      associated with both increased BMI (P=0.043) and increased PCWP (P=0.016).
      CONCLUSIONS: Obesity and its accompanying increase in left ventricular filling
      pressure were associated with lower coronary microvascular density, which may
      contribute to the lower maximal myocardial blood flow, impaired myocardial
      metabolism, diastolic dysfunction and higher risk of heart failure in obese
      individuals.

PMID- 24312360
TI  - Serine/threonine kinase 17A is a novel candidate for therapeutic targeting in
      glioblastoma.
AB  - STK17A is a relatively uncharacterized member of the death-associated protein
      family of serine/threonine kinases which have previously been associated with
      cell death and apoptosis. Our prior work established that STK17A is a novel p53
      target gene that is induced by a variety of DNA damaging agents in a p53
      dependent manner. In this study we have uncovered an additional, unanticipated
      role for STK17A as a candidate promoter of cell proliferation and survival in
      glioblastoma (GBM). Unexpectedly, it was found that STK17A is highly
      overexpressed in a grade-dependent manner in gliomas compared to normal brain and
      other cancer cell types with the highest level of expression in GBM. Knockdown of
      STK17A in GBM cells results in a dramatic alteration in cell shape that is
      associated with decreased proliferation, clonogenicity, migration, invasion and
      anchorage independent colony formation. STK17A knockdown also sensitizes GBM
      cells to genotoxic stress. STK17A overexpression is associated with a significant
      survival disadvantage among patients with glioma which is independent of age,
      molecular phenotype, IDH1 mutation, PTEN loss, and alterations in the p53 pathway
      and partially independent of grade. In summary, we demonstrate that STK17A
      provides a proliferative and survival advantage to GBM cells and is a potential
      target to be exploited therapeutically in patients with glioma. 

PMID- 24312361
TI  - Interaction of Leptospira elongation factor Tu with plasminogen and complement
      factor H: a metabolic leptospiral protein with moonlighting activities.
AB  - The elongation factor Tu (EF-Tu), an abundant bacterial protein involved in
      protein synthesis, has been shown to display moonlighting activities. Known to
      perform more than one function at different times or in different places, it is
      found in several subcellular locations in a single organism, and may serve as a
      virulence factor in a range of important human pathogens. Here we demonstrate
      that Leptospira EF-Tu is surface-exposed and performs additional roles as a cell
      surface receptor for host plasma proteins. It binds plasminogen in a dose
      dependent manner, and lysine residues are critical for this interaction. Bound
      plasminogen is converted to active plasmin, which, in turn, is able to cleave the
      natural substrates C3b and fibrinogen. Leptospira EF-Tu also acquires the
      complement regulator Factor H (FH). FH bound to immobilized EF-Tu displays
      cofactor activity, mediating C3b degradation by Factor I (FI). In this manner, EF
      Tu may contribute to leptospiral tissue invasion and complement inactivation. To
      our knowledge, this is the first description of a leptospiral protein exhibiting
      moonlighting activities. 

PMID- 24312362
TI  - Amniotic fluid deficiency and congenital abnormalities both influence fluctuating
      asymmetry in developing limbs of human deceased fetuses.
AB  - Fluctuating asymmetry (FA), as an indirect measure of developmental instability
      (DI), has been intensively studied for associations with stress and fitness.
      Patterns, however, appear heterogeneous and the underlying causes remain largely
      unknown. One aspect that has received relatively little attention in the
      literature is the consequence of direct mechanical effects on asymmetries. The
      crucial prerequisite for FA to reflect DI is that environmental conditions on
      both sides should be identical. This condition may be violated during early human
      development if amniotic fluid volume is deficient, as the resulting mechanical
      pressures may increase asymmetries. Indeed, we showed that limb bones of deceased
      human fetuses exhibited increased asymmetry, when there was not sufficient
      amniotic fluid (and, thus, space) in the uterine cavity. As amniotic fluid
      deficiency is known to cause substantial asymmetries and abnormal limb
      development, these subtle asymmetries are probably at least in part caused by the
      mechanical pressures. On the other hand, deficiencies in amniotic fluid volume
      are known to be associated with other congenital abnormalities that may disturb
      DI. More specifically, urogenital abnormalities can directly affect/reduce
      amniotic fluid volume. We disentangled the direct mechanical effects on FA from
      the indirect effects of urogenital abnormalities, the latter presumably
      representing DI. We discovered that both factors contributed significantly to the
      increase in FA. However, the direct mechanical effect of uterine pressure, albeit
      statistically significant, appeared less important than the effects of urogenital
      abnormalities, with an effect size only two-third as large. We, thus, conclude
      that correcting for the relevant direct factors allowed for a representative test
      of the association between DI and stress, and confirmed that fetuses form a
      suitable model system to increase our understanding in patterns of FA and
      symmetry development. 

PMID- 24312363
TI  - Molecular evolution of vertebrate neurotrophins: co-option of the highly
      conserved nerve growth factor gene into the advanced snake venom arsenalf.
AB  - Neurotrophins are a diverse class of structurally related proteins, essential for
      neuronal development, survival, plasticity and regeneration. They are
      characterized by major family members, such as the nerve growth factors (NGF),
      brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have
      been demonstrated here to lack coding sequence variations and follow the regime
      of negative selection, highlighting their extremely important conserved role in
      vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of
      the chemical arsenal of the venomous advanced snake family Elapidae (and to a
      lesser extent Viperidae) have characteristics consistent with the typical
      accelerated molecular evolution of venom components. This includes a rapid rate
      of diversification under the significant influence of positive-selection, with
      the majority of positively-selected sites found in the secreted beta-polypeptide
      chain (74%) and on the molecular surface of the protein (92%), while the core
      structural and functional residues remain highly constrained. Such focal
      mutagenesis generates active residues on the toxin molecular surface, which are
      capable of interacting with novel biological targets in prey to induce a myriad
      of pharmacological effects. We propose that caenophidian NGFs could participate
      in prey-envenoming by causing a massive release of chemical mediators from mast
      cells to mount inflammatory reactions and increase vascular permeability, thereby
      aiding the spread of other toxins and/or by acting as proapoptotic factors.
      Despite their presence in reptilian venom having been known for over 60 years,
      this is the first evidence that venom-secreted NGF follows the molecular
      evolutionary pattern of other venom components, and thus likely participates in
      prey-envenomation. 

PMID- 24312364
TI  - alpha7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Abeta
      effects in a preclinical Alzheimer's mouse model.
AB  - It is now recognized that astrocytes participate in synaptic communication
      through intimate interactions with neurons. A principal mechanism is through the
      release of gliotransmitters (GTs) such as ATP, D-serine and most notably,
      glutamate, in response to astrocytic calcium elevations. We and others have shown
      that amyloid-beta (Abeta), the toxic trigger for Alzheimer's disease (AD),
      interacts with hippocampal alpha7 nicotinic acetylcholine receptors (nAChRs).
      Since alpha7nAChRs are highly permeable to calcium and are expressed on
      hippocampal astrocytes, we investigated whether Abeta could activate astrocytic
      alpha7nAChRs in hippocampal slices and induce GT glutamate release. We found that
      biologically-relevant concentrations of Abeta1-42 elicited alpha7nAChR-dependent
      calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow
      inward currents (SICs) in CA1 neurons. In the Tg2576 AD mouse model for Abeta
      over-production and accumulation, we found that spontaneous astrocytic calcium
      elevations were of higher frequency compared to wildtype (WT). The frequency and
      kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly
      due to increased endogenous Abeta observed in this model. Activation of
      alpha7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal
      neurons while alpha7nAChRs on astrocytes of AD mice were abrogated. These
      findings suggest that, at an age that far precedes the emergence of cognitive
      deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits
      augmented astrocytic activity and glutamate GT release suggesting possible
      repercussions for preclinical AD hippocampal neural networks that contribute to
      subsequent cognitive decline. 

PMID- 24312365
TI  - Benthic reef primary production in response to large amplitude internal waves at
      the Similan Islands (Andaman Sea, Thailand).
AB  - Coral reefs are facing rapidly changing environments, but implications for reef
      ecosystem functioning and important services, such as productivity, are difficult
      to predict. Comparative investigations on coral reefs that are naturally exposed
      to differing environmental settings can provide essential information in this
      context. One prevalent phenomenon regularly introducing alterations in water
      chemistry into coral reefs are internal waves. This study therefore investigates
      the effect of large amplitude internal waves (LAIW) on primary productivity in
      coral reefs at the Similan Islands (Andaman Sea, Thailand). The LAIW-exposed west
      sides of the islands are subjected to sudden drops in water temperature
      accompanied by enhanced inorganic nutrient concentrations compared to the
      sheltered east. At the central island, Ko Miang, east and west reefs are only few
      hundred meters apart, but feature pronounced differences. On the west lower live
      coral cover (-38 %) coincides with higher turf algae cover (+64 %) and growth
      (+54 %) compared to the east side. Turf algae and the reef sand-associated
      microphytobenthos displayed similar chlorophyll a contents on both island sides,
      but under LAIW exposure, turf algae exhibited higher net photosynthesis (+23 %),
      whereas the microphytobenthos displayed reduced net and gross photosynthesis (-19
      % and -26 %, respectively) accompanied by lower respiration (-42 %). In contrast,
      the predominant coral Porites lutea showed higher chlorophyll a tissues contents
      (+42 %) on the LAIW-exposed west in response to lower light availability and
      higher inorganic nutrient concentrations, but net photosynthesis was comparable
      for both sides. Turf algae were the major primary producers on the west side,
      whereas microphytobenthos dominated on the east. The overall primary production
      rate (comprising all main benthic primary producers) was similar on both island
      sides, which indicates high primary production variability under different
      environmental conditions. 

PMID- 24312366
TI  - Identification of miR-30e* regulation of Bmi1 expression mediated by tumor
      associated macrophages in gastrointestinal cancer.
AB  - Bmi1 is overexpressed in a variety of human cancers including gastrointestinal
      cancer. The high expression level of Bmi1 protein is associated with poor
      prognosis of gastrointestinal cancer patients. On the other hand, tumor
      associated macrophages (TAMs) contribute to tumor growth, invasion, and
      metastasis by producing various mediators in the tumor microenvironment. The aim
      of this study was to investigate TAM-mediated regulation of Bmi1 expression in
      gastrointestinal cancer. The relationship between TAMs and Bmi1 expression was
      analyzed by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and
      results showed a positive correlation with tumor-infiltrating macrophages (CD68
      and CD163) and Bmi1 expression in cancer cells. Co-culture with TAMs triggered
      Bmi1 expression in cancer cell lines and enhanced sphere formation ability. miRNA
      microarray analysis of a gastric cancer cell line co-cultured with macrophages
      was conducted, and using in silico methods to analyze the results, we identified
      miR-30e* as a potential regulator of Bmi1 expression. Luciferase assays using miR
      30e* mimic revealed that Bmi1 was a direct target for miR-30e* by interactions
      with the putative miR-30e* binding sites in the Bmi1 3' untranslated region. qRT
      PCR analysis of resected cancer specimens showed that miR-30e* expression was
      downregulated in tumor regions compared with non-tumor regions, and Bmi1
      expression was inversely correlated with miR-30e* expression in gastric cancer
      tissues, but not in colon cancer tissues. Our findings suggest that TAMs may
      cause increased Bmi1 expression through miR-30e* suppression, leading to tumor
      progression. The suppression of Bmi1 expression mediated by TAMs may thus
      represent a possible strategy as the treatment of gastrointestinal cancer. 

PMID- 24312367
TI  - Neuraminidase subtyping of avian influenza viruses with PrimerHunter-designed
      primers and quadruplicate primer pools.
AB  - We have previously developed a software package called PrimerHunter to design
      primers for PCR-based virus subtyping. In this study, 9 pairs of primers were
      designed with PrimerHunter and successfully used to differentiate the 9
      neuraminidase (NA) genes of avian influenza viruses (AIVs) in multiple PCR-based
      assays. Furthermore, primer pools were designed and successfully used to decrease
      the number of reactions needed for NA subtyping from 9 to 4. The quadruplicate
      primer-pool method is cost-saving, and was shown to be suitable for the NA
      subtyping of both cultured AIVs and uncultured AIV swab samples. The primers
      selected for this study showed excellent sensitivity and specificity in NA
      subtyping by RT-PCR, SYBR green-based Real-time PCR and Real-time RT-PCR methods.
      AIV RNA of 2 to 200 copies (varied by NA subtypes) could be detected by these
      reactions. No unspecific amplification was displayed when detecting RNAs of other
      avian infectious viruses such as Infectious bronchitis virus, Infectious bursal
      disease virus and Newcastle disease virus. In summary, this study introduced
      several sensitive and specific PCR-based assays for NA subtyping of AIVs and also
      validated again the effectiveness of the PrimerHunter tool for the design of
      subtyping primers. 

PMID- 24312368
TI  - 32 species validation of a new Illumina paired-end approach for the development
      of microsatellites.
AB  - Development and optimization of novel species-specific microsatellites, or simple
      sequence repeats (SSRs) remains an important step for studies in ecology,
      evolution, and behavior. Numerous approaches exist for identifying new SSRs that
      vary widely in terms of both time and cost investments. A recent approach of
      using paired-end Illumina sequence data in conjunction with the bioinformatics
      pipeline, PAL_FINDER, has the potential to substantially reduce the cost and
      labor investment while also improving efficiency. However, it does not appear
      that the approach has been widely adopted, perhaps due to concerns over its broad
      applicability across taxa. Therefore, to validate the utility of the approach we
      developed SSRs for 32 species representing 30 families, 25 orders, 11 classes,
      and six phyla and optimized SSRs for 13 of the species. Overall the IPE method
      worked extremely well and we identified 1000s of SSRs for all species (mean =
      128,485), with 17% of loci being potentially amplifiable loci, and 25% of these
      met our most stringent criteria designed to that avoid SSRs associated with
      repetitive elements. Approximately 61% of screened primers yielded strong
      amplification of a single locus. 

PMID- 24312369
TI  - LPS-binding protein and IL-6 mark paradoxical tuberculosis immune reconstitution
      inflammatory syndrome in HIV patients.
AB  - BACKGROUND: Tuberculosis-associated immune reconstitution inflammatory syndrome
      (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients
      initiating antiretroviral therapy (ART). The role of the innate immune system in
      TB-IRIS is becoming increasingly apparent, however the potential involvement in
      TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by
      binding PAMPs has not been investigated before. Here we aimed to investigate the
      innate nature of the cytokine response in TB-IRIS and to identify novel potential
      biomarkers. METHODS: From a large prospective cohort of HIV-TB co-infected
      patients receiving TB treatment, we compared 40 patients who developed TB-IRIS
      during the first month of ART with 40 patients matched for age, sex and baseline
      CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)
      binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid
      binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and
      during ART. RESULTS: We observed lower baseline levels of IL-6 (p = 0.041), GCSF
      (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected
      higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p <= 0.032) and
      lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL
      6 showed an independent effect in multivariate models containing significant
      cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034). CONCLUSION: We
      report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during
      IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of
      the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds
      a distinct role in the disturbed innate cytokine profile before and during TB
      IRIS. Future clinical studies should investigate the importance and clinical
      relevance of these markers for the diagnosis and treatment of TB-IRIS.

PMID- 24312370
TI  - Positive evolutionary selection on the RIG-I-like receptor genes in mammals.
AB  - The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H
      box RNA helicases responsible for the cytoplasmic detection of viral RNA. These
      receptors detect a variety of RNA viruses, or DNA viruses that express unusual
      RNA species, many of which are responsible for a great number of severe and
      lethal diseases. Host innate sentinel proteins involved in pathogen recognition
      must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected
      to long-term positive selection pressures to avoid potential infections. Using
      six codon-based Maximum Likelihood methods, we were able to identify specific
      codons under positive selection in each of these three genes. The highest number
      of positively selected codons was detected in MDA5, but a great percentage of
      these codons were located outside of the currently defined protein domains for
      MDA5, which likely reflects the imposition of both functional and structural
      constraints. Additionally, our results support LGP2 as being the least prone to
      evolutionary change, since the lowest number of codons under selection was
      observed for this gene. On the other hand, the preponderance of positively
      selected codons for RIG-I were detected in known protein functional domains,
      suggesting that pressure has been imposed by the vast number of viruses that are
      recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the
      region responsible for recognizing and binding to its RNA substrates, exhibited
      the strongest evidence of selective pressures. Branch-site analyses were
      performed and several species branches on the three receptor gene trees showed
      evidence of episodic positive selection. In conclusion, by looking for evidence
      of positive evolutionary selection on mammalian RIG-I-like receptor genes, we
      propose that a multitude of viruses have crafted the receptors biological
      function in host defense, specifically for the RIG-I gene, contributing to the
      innate species-specific resistance/susceptibility to diverse viral pathogens. 

PMID- 24312371
TI  - Alteration of de novo glucose production contributes to fasting hypoglycaemia in
      Fyn deficient mice.
AB  - Previous studies have demonstrated that glucose disposal is increased in the Fyn
      knockout (FynKO) mice due to increased insulin sensitivity. FynKO mice also
      display fasting hypoglycaemia despite decreased insulin levels, which suggested
      that hepatic glucose production was unable to compensate for the increased basal
      glucose utilization. The present study investigates the basis for the reduction
      in plasma glucose levels and the reduced ability for the liver to produce glucose
      in response to gluconeogenic substrates. FynKO mice had a 5-fold reduction in
      phosphoenolpyruvate carboxykinase (PEPCK) gene and protein expression and a
      marked reduction in pyruvate, pyruvate/lactate-stimulated glucose output.
      Remarkably, de novo glucose production was also blunted using gluconeogenic
      substrates that bypass the PEPCK step. Impaired conversion of glycerol to glucose
      was observed in both glycerol tolerance test and determination of the conversion
      of (13)C-glycerol to glucose in the fasted state. alpha-glycerol phosphate levels
      were reduced but glycerol kinase protein expression levels were not changed.
      Fructose-driven glucose production was also diminished without alteration of
      fructokinase expression levels. The normal levels of dihydroxyacetone phosphate
      and glyceraldehyde-3-phosphate observed in the FynKO liver extracts suggested
      normal triose kinase function. Fructose-bisphosphate aldolase (aldolase) mRNA or
      protein levels were normal in the Fyn-deficient livers, however, there was a
      large reduction in liver fructose-6-phosphate (30-fold) and fructose-1,6
      bisphosphate (7-fold) levels as well as a reduction in glucose-6-phosphate (2
      fold) levels. These data suggest a mechanistic defect in the allosteric
      regulation of aldolase activity. 

PMID- 24312372
TI  - Seroprevalence of cytomegalovirus, Epstein Barr virus and varicella zoster virus
      among pregnant women in Bradford: a cohort study.
AB  - OBJECTIVE: To estimate the seroprevalence of cytomegalovirus (CMV), Epstein Barr
      virus (EBV) and varicella zoster virus (VZV) among pregnant women in Bradford by
      ethnic group and country of birth. METHODS: A stratified random sample of 949
      pregnant women enrolled in the Born in Bradford birth cohort was selected to
      ensure sufficient numbers of White UK born women, Asian UK born women and Asian
      women born in Asia. Serum samples taken at 24-28 weeks' gestation were tested for
      CMV IgG, EBV IgG and VZV IgG. Each woman completed a questionnaire which included
      socio-demographic information. RESULTS: CMV seroprevalence was 49% among the
      White British women, 89% among South Asian UK born women and 98% among South
      Asian women born in South Asia. These differences remained after adjusting for
      socio-demographic factors. In contrast, VZV seroprevalence was 95% among women
      born in the UK but significantly lower at 90% among South Asian women born in
      Asia. EBV seroprevalence was 94% overall and did not vary by ethnic group/country
      of birth. CONCLUSIONS: Although about half of White British women are at risk of
      primary CMV infection in pregnancy and the associated increased risk of
      congenital infection, most congenital CMV infections are likely to be in children
      born to South Asian women with non-primary infection during pregnancy. South
      Asian women born in South Asia are at risk of VZV infection during pregnancy
      which could produce congenital varicella syndrome or perinatal chickenpox.
      Differences in CMV and VZV seroprevalence by ethnic group and country of birth
      must be taken into account when universal immunisation against these viruses is
      contemplated.

PMID- 24312373
TI  - Normal autophagic activity in macrophages from mice lacking Galphai3, AGS3, or
      RGS19.
AB  - In macrophages autophagy assists antigen presentation, affects cytokine release,
      and promotes intracellular pathogen elimination. In some cells autophagy is
      modulated by a signaling pathway that employs Galphai3, Activator of G-protein
      Signaling-3 (AGS3/GPSM1), and Regulator of G-protein Signaling 19 (RGS19). As
      macrophages express each of these proteins, we tested their importance in
      regulating macrophage autophagy. We assessed LC3 processing and the formation of
      LC3 puncta in bone marrow derived macrophages prepared from wild type, Gnai3(-/
      ), Gpsm1(-/-), or Rgs19(-/-) mice following amino acid starvation or Nigericin
      treatment. In addition, we evaluated rapamycin-induced autophagic proteolysis
      rates by long-lived protein degradation assays and anti-autophagic action after
      rapamycin induction in wild type, Gnai3(-/-), and Gpsm1(-/-) macrophages. In
      similar assays we compared macrophages treated or not with pertussis toxin, an
      inhibitor of GPCR (G-protein couple receptor) triggered Galphai nucleotide
      exchange. Despite previous findings, the level of basal autophagy, autophagic
      induction, autophagic flux, autophagic degradation and the anti-autophagic action
      in macrophages that lacked Galphai3, AGS3, or RGS19; or had been treated with
      pertussis toxin, were similar to controls. These results indicate that while
      Galphai signaling may impact autophagy in some cell types it does not in
      macrophages. 

PMID- 24312374
TI  - Profiling inflammatory responses with microfluidic immunoblotting.
AB  - Rapid profiling of signaling pathways has been a long sought after goal in
      biological sciences and clinical medicine. To understand these signaling
      pathways, their protein components must be profiled. The protein components of
      signaling pathways are typically profiled with protein immunoblotting. Protein
      immunoblotting is a powerful technique but has several limitations including the
      large sample requirements, high amounts of antibody, and limitations in assay
      throughput. To overcome some of these limitations, we have designed a
      microfluidic protein immunoblotting device to profile multiple signaling pathways
      simultaneously. We show the utility of this approach by profiling inflammatory
      signaling pathways (NFkappaB, JAK-STAT, and MAPK) in cell models and human
      samples. The microfluidic immunoblotting device can profile proteins and protein
      modifications with 5380-fold less antibody compared to traditional protein
      immunoblotting. Additionally, this microfluidic device interfaces with commonly
      available immunoblotting equipment, has the ability to multiplex, and is
      compatible with several protein detection methodologies. We anticipate that this
      microfluidic device will complement existing techniques and is well suited for
      life science applications. 

PMID- 24312375
TI  - Blood erythrocyte concentrations of cadmium and lead and the risk of B-cell non
      Hodgkin's lymphoma and multiple myeloma: a nested case-control study.
AB  - BACKGROUND: Cadmium (Cd) and lead (Pb) are hypothesised to be risk factors for
      non-Hodgkin's lymphoma (NHL), a group of haematological malignancies with a
      suspected environmental aetiology. Within the EnviroGenoMarkers study we utilised
      pre-diagnostic erythrocyte concentrations of Cd and Pb to determine whether
      exposure was associated with risk of B-cell NHL and multiple myeloma. METHODS:
      194 incident cases of B-cell NHL and 76 cases of multiple myeloma diagnosed
      between 1990 and 2006 were identified from two existing cohorts; EPIC-Italy and
      the Northern Sweden Health and Disease Study. Cases were matched to healthy
      controls by centre, age, gender and date of blood collection. Cd and Pb were
      measured in blood samples provided at recruitment using inductively coupled
      plasma-mass spectrometry. Logistic regression was applied to assess the
      association with risk. Analyses were stratified by cohort and gender and by
      subtype where possible. RESULTS: There was little evidence of an increased risk
      of B-cell NHL or multiple myeloma with exposure to Cd (B-cell NHL: OR 1.09 95%CI
      0.61, 1.93, MM: OR 1.16 95% CI: 0.40, 3.40 ) or Pb (B-cell NHL: 0.93 95% CI 0.43,
      2.02, multiple myeloma: OR 1.63 95%CI 0.45, 5.94) in the total population when
      comparing the highest to the lowest quartile of exposure. However, gender and
      cohort specific differences in results were observed. In females the risk of B
      cell NHL was more than doubled in those with a body burden of Cd >1 ug/L (OR 2.20
      95%CI; 1.04, 4.65). CONCLUSIONS: This nested case-control study does not support
      a consistent positive association between Cd or Pb and NHL, but there is some
      indication of a gender specific effect suggesting further research is warranted.

PMID- 24312376
TI  - Incidence and risk of treatment-related mortality with anti-epidermal growth
      factor receptor monoclonal antibody in cancer patients: a meta-analysis of 21
      randomized controlled trials.
AB  - BACKGROUND: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies
      (MoAbs) cetuximab and panitumumab have emerged as an effective targeted therapy
      in the treatment of cancer patients, but the overall incidence and risk of fatal
      adverse events (FAEs) associated with these agents is still unclear. METHODS:
      Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up
      to May 31, 2013 were searched to identify relevant studies. Eligible studies
      included prospective randomized controlled trials evaluating MoAbs in cancer
      patients with adequate data on FAEs. Statistical analyses were conducted to
      calculate the summary incidence, odds ratio and 95% confidence intervals (CIs) by
      using either random effects or fixed effect models according to the heterogeneity
      of included studies. RESULTS: A total of 14,776 patients with a variety of solid
      tumors from 21 clinical trials were included in our analysis. The overall
      incidence of MoAbs associated FAEs was 1.7% (95%CI: 1.1-2.5%), and the incidence
      of cetuximab-related FAEs was higher than that of panitumumab (2.0% versus 0.9%).
      Compared with the controls, the use of MoAbs was associated with a significantly
      increased risk of FAEs, with an OR of 1.37 (95%CI: 1.04-1.81, p=0.024). Subgroup
      analysis based on EGFR-MoAbs drugs, phase of trials and tumor types demonstrated
      a tendency to increase the risk of FAEs, but the risk did not increase in breast
      cancer, esophagus cancer and phase II trials. CONCLUSIONS: With present evidence,
      the use of EGFR-MoAbs is associated with an increased risk of FAEs in patients
      with advanced solid tumors.

PMID- 24312377
TI  - Proteomic and genomic analyses of antimony resistant Leishmania infantum mutant.
AB  - BACKGROUND: Antimonials remain the primary antileishmanial drugs in most
      developing countries. However, drug resistance to these compounds is increasing
      and our understanding of resistance mechanisms is partial. METHODS/PRINCIPAL
      FINDINGS: In the present study, quantitative proteomics using stable isotope
      labelling of amino acids in cell culture (SILAC) and genome next generation
      sequencing were used in order to better characterize in vitro generated
      Leishmania infantum antimony resistant mutant (Sb2000.1). Using the proteomic
      method, 58 proteins were found to be differentially regulated in Sb2000.1. The
      ABC transporter MRPA (ABCC3), a known marker of antimony resistance, was observed
      for the first time in a proteomic screen. Furthermore, transfection of its gene
      conferred antimony resistance in wild-type cells. Next generation sequencing
      revealed aneuploidy for 8 chromosomes in Sb2000.1. Moreover, specific amplified
      regions derived from chromosomes 17 and 23 were observed in Sb2000.1 and a single
      nucleotide polymorphism (SNP) was detected in a protein kinase (LinJ.33.1810
      E629K). CONCLUSION/SIGNIFICANCE: Our results suggest that differentially
      expressed proteins, chromosome number variations (CNVs), specific gene
      amplification and SNPs are important features of antimony resistance in
      Leishmania.

PMID- 24312378
TI  - Caveolae-dependent and -independent uptake of albumin in cultured rodent
      pulmonary endothelial cells.
AB  - Although a critical role for caveolae-mediated albumin transcytosis in pulmonary
      endothelium is well established, considerably less is known about caveolae
      independent pathways. In this current study, we confirmed that cultured rat
      pulmonary microvascular (RPMEC) and pulmonary artery (RPAEC) endothelium
      endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode
      and internalization resulted in co-localization by fluorescence microscopy with
      cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1) in RPAEC
      significantly inhibited albumin uptake, a remnant portion of albumin uptake was
      cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we
      isolated and cultured mouse lung endothelial cells (MLEC) from wild type and cav
      1(-/-) mice and noted that ~ 65% of albumin uptake, as determined by confocal
      imaging or live cell total internal reflectance fluorescence microscopy (TIRF),
      persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was
      evaluated by electron microscopy and demonstrated that albumin uptake in MLEC
      from cav-1(-/-) mice was through caveolae-independent pathway(s) including
      clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally,
      we noted that albumin uptake in RPMEC was in part sensitive to pharmacological
      agents (amiloride [sodium transport inhibitor], Go6976 [protein kinase C
      inhibitor], and cytochalasin D [inhibitor of actin polymerization]) consistent
      with a macropinocytosis-like process. The amiloride sensitivity accounting for
      macropinocytosis also exists in albumin uptake by both wild type and cav-1(-/-)
      MLEC. We conclude from these studies that in addition to the well described
      caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion
      of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears
      to involve clathrin-mediated endocytosis and macropinocytosis-like process. 

PMID- 24312379
TI  - Oral leptin treatment in suckling rats ameliorates detrimental effects in
      hypothalamic structure and function caused by maternal caloric restriction during
      gestation.
AB  - A poor prenatal environment brings about perturbations in leptin surge and
      hypothalamic circuitry that program impaired ability to regulate energy
      homeostasis in adulthood. Here, using a rat model of moderate maternal caloric
      restriction during gestation, we aimed to investigate whether leptin
      supplementation with physiological doses throughout lactation is able to
      ameliorate the adverse developmental malprogramming effects exerted in offspring
      hypothalamus structure and function. Three groups of male and female rats were
      studied: the offspring of ad libitum fed dams (controls), the offspring of 20%
      calorie restricted dams during the first part of pregnancy (CR), and CR rats
      supplemented with physiological doses of leptin throughout lactation (CR-Leptin).
      Animals were sacrificed on postnatal day 25. Morphometric and immunohistochemical
      studies on arcuate (ARC) and paraventicular (PVN) nucleus were performed and
      hypothalamic expression levels of selected genes were determined. In CR males,
      leptin treatment restored, at least in part, the number of immunoreactive
      neuropeptide Y (NPY(+)) cells in ARC, the total number of cells in PVN,
      hypothalamic NPY, cocaine- and amphetamine-regulated transcript (CART) and
      suppressor of cytokine signalling-3 (SOCS-3) mRNA levels, and plasma leptin
      levels, which were decreased in CR animals. CR-Leptin males showed higher
      hypothalamic long-form leptin receptor (ObRb) mRNA levels, compared to control
      and CR animals. In CR females, leptin treatment reverted the increased number of
      cells in ARC and cell density in ARC and PVN, and reduced hypothalamic SOCS-3
      mRNA expression to levels similar to controls. Leptin treatment also reverted the
      increased relative area of NPY(+) fibers in the PVN occurring in CR animals. In
      conclusion, leptin supplementation throughout lactation is able to revert, at
      least partly, most of the developmental effects on hypothalamic structure and
      function caused by moderate maternal caloric restriction during gestation, and
      hence making this metabolic malprogramming reversible to some extent. 

PMID- 24312380
TI  - Barriers to and facilitators of research utilization: a survey of registered
      nurses in China.
AB  - AIMS: This survey aims to describe the perception of barriers to and facilitators
      of research utilization by registered nurses in Sichuan province, China, and to
      explore the factors influencing the perceptions of the barriers to and
      facilitators of research utilization. METHODS: A cross sectional survey design
      and a double cluster sampling method were adopted. A total of 590 registered
      nurses from 3 tertiary level hospitals in Sichuan province, China, were recruited
      in a period from September 2006 to January 2007. A modified BARRUERS Scale and a
      Facilitators Scale were used. Data were analyzed with descriptive statistics,
      rank transformation test, and multiple linear regression. RESULTS: Barriers
      related to the setting subscale were more influential than barriers related to
      other subscales. The lack of authority was ranked as the top greatest barrier
      (15.7%), followed by the lack of time (13.4%) and language barrier (15.0%).
      Additional barriers identified were the reluctance of patients to research
      utilization, the lack of funding, and the lack of legal protection. The top three
      greatest facilitators were enhancing managerial support (36.9%), advancing
      education to increase knowledge base (21.1%), and increasing time for reviewing
      and implementing (17.5%), while cooperation of patients to research utilization,
      establishing a panel to evaluate researches, and funding were listed as
      additional facilitators. Hospital, educational background, research experience,
      and knowledge on evidence-based nursing were the factors influencing perceptions
      of the barriers and facilitators. CONCLUSIONS: Nurses in China are facing a
      number of significant barriers in research utilization. Enhancing managerial
      support might be the most promising facilitator, given Chinese traditional
      culture and existing health care system. Hospital, educational background,
      research experience and knowledge on evidence-based nursing should be taken into
      account to promote research utilization. The BARRIERS Scale should consider
      funding and involvement of patients in research utilization.

PMID- 24312381
TI  - FABP4 induces vascular smooth muscle cell proliferation and migration through a
      MAPK-dependent pathway.
AB  - PURPOSE: The migration and proliferation of vascular smooth muscle cells play
      crucial roles in the development of atherosclerotic lesions. This study examined
      the effects of fatty acid binding protein 4 (FABP4), an adipokine that is
      associated with cardiovascular risk, endothelial dysfunction and proinflammatory
      effects, on the migration and proliferation of human coronary artery smooth
      muscle cells (HCASMCs). METHODS AND RESULTS: A DNA 5-bromo-2'-deoxy-uridine
      (BrdU) incorporation assay indicated that FABP4 significantly induced the dose
      dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml
      (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml)
      significantly inhibited the induced cell proliferation, demonstrating the
      specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC
      migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs.
      unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4
      significantly increased cell migration compared with unstimulated cells from 4 h
      (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5
      uM) and PD98059 (10 uM) blocked the FABP4-induced proliferation and migration of
      HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we
      observed an up-regulation of the MAPK pathway without activation of Akt. We found
      that FABP4 induced the active forms of the nuclear transcription factors c-jun
      and c-myc, which are regulated by MAPK cascades, and increased the expression of
      the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are
      involved in cell cycle regulation and cell migration. CONCLUSIONS: These findings
      indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs,
      suggesting a role for this adipokine in vascular remodelling. Taken together,
      these results demonstrate that the FABP4-induced DNA synthesis and cell migration
      are mediated primarily through a MAPK-dependent pathway that activates the
      transcription factors c-jun and c-myc in HCASMCs.

PMID- 24312382
TI  - Effect of replacing sugar with non-caloric sweeteners in beverages on the reward
      value after repeated exposure.
AB  - BACKGROUND: The reward value of food is partly dependent on learned associations.
      It is not yet known whether replacing sugar with non-caloric sweeteners in food
      is affecting long-term acceptance. OBJECTIVE: To determine the effect of
      replacing sugar with non-caloric sweeteners in a nutrient-empty drink (soft
      drink) versus nutrient-rich drink (yoghurt drink) on reward value after repeated
      exposure. DESIGN: We used a randomized crossover design whereby forty subjects
      (15 men, 25 women) with a mean +/- SD age of 21 +/- 2 y and BMI of 21.5 +/- 1.7
      kg/m(2) consumed a fixed portion of a non-caloric sweetened (NS) and sugar
      sweetened (SS) versions of either a soft drink or a yoghurt drink
      (counterbalanced) for breakfast which were distinguishable by means of colored
      labels. Each version of a drink was offered 10 times in semi-random order. Before
      and after conditioning the reward value of the drinks was assessed using
      behavioral tasks on wanting, liking, and expected satiety. In a subgroup (n=18)
      fMRI was performed to assess brain reward responses to the drinks. RESULTS:
      Outcomes of both the behavioral tasks and fMRI showed that conditioning did not
      affect the reward value of the NS and SS versions of the drinks significantly.
      Overall, subjects preferred the yoghurt drinks to the soft drinks and the ss
      drinks to the NS drinks. In addition, they expected the yoghurt drinks to be more
      satiating, they reduced hunger more, and delayed the first eating episode more.
      Conditioning did not influence these effects. CONCLUSION: Our study showed that
      repeated consumption of a non-caloric sweetened beverage, instead of a sugar
      sweetened version, appears not to result in changes in the reward value. It
      cannot be ruled out that learned associations between sensory attributes and food
      satiating capacity which developed preceding the conditioning period, during
      lifetime, affected the reward value of the drinks.

PMID- 24312383
TI  - The association between fish consumption and risk of renal cancer: a meta
      analysis of observational studies.
AB  - BACKGROUND: Several case-control studies and cohort studies have investigated the
      association between fish intake and renal cancer risk, however, they yielded
      conflicting results. To our knowledge, a comprehensive assessment of the
      association between fish consumption and risk of renal cancer has not been
      reported. Hence, we conducted a systematic literature search and meta-analysis to
      quantify the association between fish consumption and renal cancer. METHODS: A
      systematic search was performed using the PubMed, Embase, and Cochrane Library
      Central database for case-control and cohort studies that assessed fish intake
      and risk of renal cancer. Two authors independently assessed eligibility and
      extracted data. Fixed-effect and random-effect models were used to estimate
      summary relative risks (RR) and the corresponding 95% confidence intervals (CIs).
      Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also
      performed. RESULTS: A total of 12 case-control studies and three cohort studies
      published between 1990 and 2011 were included in the meta-analysis, involving
      9,324 renal cancer cases and 608,753 participants. Meta-analysis showed that fish
      consumption did not significantly affect the risk of renal cancer (RR=0.99, 95%
      CI [0.92,1.07]). In our subgroup analyses, the results were not substantially
      affected by study design, region, gender, and confounder adjustments.
      Furthermore, sensitivity analysis confirmed the stability of results.
      CONCLUSIONS: The present meta-analysis suggested that there was no significant
      association between fish consumption and risk of renal cancer. More in-depth
      studies are warranted to report more detailed results, including stratified
      results by fish type, preparation method, and gender.

PMID- 24312384
TI  - Concerted suppression of STAT3 and GSK3beta is involved in growth inhibition of
      non-small cell lung cancer by Xanthatin.
AB  - Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L.,
      possesses prominent anticancer activity. We found that disruption of GSK3beta
      activity was essential for xanthatin to exert its anticancer properties in non
      small cell lung cancer (NSCLC), concurrent with preferable suppression of
      constitutive activation of STAT3. Interestingly, inactivation of the two signals
      are two mutually exclusive events in xanthatin-induced cell death. Moreover, we
      surprisingly found that exposure of xanthatin failed to trigger the presumable
      side effect of canonical Wnt/beta-Catenin followed by GSK3beta inactivation. We
      further observed that the downregulation of STAT3 was required for xanthatin to
      fine-tune the risk. Thus, the discovery of xanthatin, which has ability to
      simultaneously orchestrate two independent signaling cascades, may have important
      implications for screening promising drugs in cancer therapies. 

PMID- 24312385
TI  - Reticulated origin of domesticated emmer wheat supports a dynamic model for the
      emergence of agriculture in the fertile crescent.
AB  - We used supernetworks with datasets of nuclear gene sequences and novel markers
      detecting retrotransposon insertions in ribosomal DNA loci to reassess the
      evolutionary relationships among tetraploid wheats. We show that domesticated
      emmer has a reticulated genetic ancestry, sharing phylogenetic signals with wild
      populations from all parts of the wild range. The extent of the genetic
      reticulation cannot be explained by post-domestication gene flow between
      cultivated emmer and wild plants, and the phylogenetic relationships among
      tetraploid wheats are incompatible with simple linear descent of the domesticates
      from a single wild population. A more parsimonious explanation of the data is
      that domesticated emmer originates from a hybridized population of different wild
      lineages. The observed diversity and reticulation patterns indicate that wild
      emmer evolved in the southern Levant, and that the wild emmer populations in
      south-eastern Turkey and the Zagros Mountains are relatively recent reticulate
      descendants of a subset of the Levantine wild populations. Based on our results
      we propose a new model for the emergence of domesticated emmer. During a pre
      domestication period, diverse wild populations were collected from a large area
      west of the Euphrates and cultivated in mixed stands. Within these cultivated
      stands, hybridization gave rise to lineages displaying reticulated genealogical
      relationships with their ancestral populations. Gradual movement of early farmers
      out of the Levant introduced the pre-domesticated reticulated lineages to the
      northern and eastern parts of the Fertile Crescent, giving rise to the local wild
      populations but also facilitating fixation of domestication traits. Our model is
      consistent with the protracted and dispersed transition to agriculture indicated
      by the archaeobotanical evidence, and also with previous genetic data affiliating
      domesticated emmer with the wild populations in southeast Turkey. Unlike other
      protracted models, we assume that humans played an intuitive role throughout the
      process. 

PMID- 24312386
TI  - The association between two microRNA variants (miR-499, miR-149) and
      gastrointestinal cancer risk: a meta-analysis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that regulate the
      expression of corresponding messenger RNAs (mRNAs). Single nucleotide
      polymorphisms (SNPs) in miRNAs may contribute to cancer susceptibility due to
      changes in the microRNA's properties and/or maturation. The present study aimed
      to investigate the association between two miRNA polymorphisms (miR-499 rs3746444
      and miR-149 rs2292832) and gastrointestinal (GI) cancer risk.
      METHODOLOGY/PRINCIPAL FINDINGS: We conducted a search of case-control studies in
      PubMed, Wiley Online Library, Web of Science and the CNKI database. Eleven
      rs3746444 studies and six rs2292832 studies were included in our meta-analysis.
      The only obvious association between the miR-499 polymorphism and colorectal
      cancer susceptibility was found in the homozygote comparison (GG vs. AA: OR =
      1.66, 95% CI: 1.02-2.70, P(h) = 0.10, P = 0.04). No significant association was
      found in the subgroup analysis for ethnicity and risk of hepatocellular and
      gastric cancer. A marginally elevated GI cancer risk was discovered in the
      recessive model for miR-149 (TT vs. TC+CC: OR = 1.15, 95% CI: 1.03-1.30, P(h) =
      0.68, P = 0.02). Stratifying the results by ethnicity revealed a slight
      association between the recessive model and the Asian population (TT vs. TC+CC:
      OR = 1.14, 95% CI: 1.01-1.29, P(h) = 0.79, P = 0.03). CONCLUSIONS/SIGNIFICANCE:
      The present meta-analysis indicates that miR-499 may be associated with the risk
      to colorectal cancer. MiR-149 may confer a marginally increased risk of
      susceptibility to gastrointestinal cancer, especially for Asians.

PMID- 24312388
TI  - Identification and comparison of anti-inflammatory ingredients from different
      organs of Lotus nelumbo by UPLC/Q-TOF and PCA coupled with a NF-kappaB reporter
      gene assay.
AB  - Lotus nelumbo (LN) (Nelumbo nucifera Gaertn.) is an aquatic crop that is widely
      distributed throughout Asia and India, and various parts of this plant are edible
      and medicinal. It is noteworthy that different organs of this plant are used in
      traditional herbal medicine or folk recipes to cure different diseases and to
      relieve their corresponding symptoms. The compounds that are contained in each
      organ, which are named based on their chemical compositions, have led to their
      respective usages. In this work, a strategy was used to identify the difference
      ingredients and screen for Nuclear-factor-kappaB (NF-kappaB) inhibitors with anti
      inflammatory ability in LN. Seventeen main difference ingredients were compared
      and identified from 64 samples of 4 different organs by ultra-performance liquid
      chromatography that was coupled with quadrupole/time of flight mass spectrometry
      (UPLC/Q-TOF-MS) with principal component analysis (PCA). A luciferase reporter
      assay system combined with the UPLC/Q-TOF-MS information was applied to screen
      biologically active substances. Ten NF-kappaB inhibitors from Lotus plumule (LP)
      extracts, most of which were isoquinoline alkaloids or flavone C-glycosides, were
      screened. Heat map results showed that eight of these compounds were abundant in
      the LP. In conclusion, the LP extracts were considered to have the best anti
      inflammatory ability of the four LN organs, and the chemical material basis (CMB)
      of this biological activity was successfully validated by multivariate
      statistical analysis and biological research methods. 

PMID- 24312387
TI  - Soy, red clover, and isoflavones and breast cancer: a systematic review.
AB  - BACKGROUND: Soy and red clover isoflavones are controversial due to purported
      estrogenic activity and possible effects on breast cancer. We conducted a
      systematic review of soy and red clover for efficacy in improving menopausal
      symptoms in women with breast cancer, and for potential impact on risk of breast
      cancer incidence or recurrence. METHODS: We searched MEDLINE, Embase, the
      Cochrane Library, and AMED from inception to March 2013 for human interventional
      or observational data pertaining to the safety and efficacy of soy and red clover
      isoflavones in patients with or at risk of breast cancer. RESULTS: Of 4179
      records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials,
      and 80 observational studies. Five RCTs reported on the efficacy of soy for hot
      flashes, showing no significant reductions in hot flashes compared to placebo.
      There is lack of evidence showing harm from use of soy with respect to risk of
      breast cancer or recurrence, based on long term observational data. Soy intake
      consistent with that of a traditional Japanese diet (2-3 servings daily,
      containing 25-50mg isoflavones) may be protective against breast cancer and
      recurrence. Human trials show that soy does not increase circulating estradiol or
      affect estrogen-responsive target tissues. Prospective data of soy use in women
      taking tamoxifen does not indicate increased risk of recurrence. Evidence on red
      clover is limited, however existing studies suggest that it may not possess
      breast cancer-promoting effects. CONCLUSION: Soy consumption may be associated
      with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does
      not have estrogenic effects in humans. Soy intake consistent with a traditional
      Japanese diet appears safe for breast cancer survivors. While there is no clear
      evidence of harm, better evidence confirming safety is required before use of
      high dose (>= 100 mg) isoflavones can be recommended for breast cancer patients.

PMID- 24312389
TI  - Both positive and negative selection pressures contribute to the polymorphism
      pattern of the duplicated human CYP21A2 gene.
AB  - The human steroid 21-hydroxylase gene (CYP21A2) participates in cortisol and
      aldosterone biosynthesis, and resides together with its paralogous (duplicated)
      pseudogene in a multiallelic copy number variation (CNV), called RCCX CNV.
      Concerted evolution caused by non-allelic gene conversion has been described in
      great ape CYP21 genes, and the same conversion activity is responsible for a
      serious genetic disorder of CYP21A2, congenital adrenal hyperplasia (CAH). In the
      current study, 33 CYP21A2 haplotype variants encoding 6 protein variants were
      determined from a European population. CYP21A2 was shown to be one of the most
      diverse human genes (HHe=0.949), but the diversity of intron 2 was greater still.
      Contrary to previous findings, the evolution of intron 2 did not follow concerted
      evolution, although the remaining part of the gene did. Fixed sites (different
      fixed alleles of sites in human CYP21 paralogues) significantly accumulated in
      intron 2, indicating that the excess of fixed sites was connected to the lack of
      effective non-allelic conversion and concerted evolution. Furthermore, positive
      selection was presumably focused on intron 2, and possibly associated with the
      previous genetic features. However, the positive selection detected by several
      neutrality tests was discerned along the whole gene. In addition, the clear
      signature of negative selection was observed in the coding sequence. The
      maintenance of the CYP21 enzyme function is critical, and could lead to negative
      selection, whereas the presumed gene regulation altering steroid hormone levels
      via intron 2 might help fast adaptation, which broadly characterizes the genes of
      human CNVs responding to the environment. 

PMID- 24312390
TI  - Cerebrospinal fluid (CSF) 25-hydroxyvitamin D concentration and CSF
      acetylcholinesterase activity are reduced in patients with Alzheimer's disease.
AB  - BACKGROUND: Little is known of vitamin D concentration in cerebrospinal fluid
      (CSF) in Alzheimer's disease (AD) and its relation with CSF acetylcholinesterase
      (AChE) activity, a marker of cholinergic function. METHODS: A cross-sectional
      study of 52 consecutive patients under primary evaluation of cognitive impairment
      and 17 healthy controls. The patients had AD dementia or mild cognitive
      impairment (MCI) diagnosed with AD dementia upon follow-up (n = 28), other
      dementias (n = 12), and stable MCI (SMCI, n = 12). We determined serum and CSF
      concentrations of calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D
      (25OHD), and CSF activities of AChE and butyrylcholinesterase (BuChE). FINDINGS:
      CSF 25OHD level was reduced in AD patients (P < 0.05), and CSF AChE activity was
      decreased both in patients with AD (P < 0.05) and other dementias (P < 0.01)
      compared to healthy controls. None of the measured variables differed between
      BuChE K-variant genotypes whereas the participants that were homozygous in terms
      of the apolipoprotein E (APOE) epsilon4 allele had decreased CSF AChE activity
      compared to subjects lacking the APOE epsilon4 allele (P = 0.01). In AD patients
      (n=28), CSF AChE activity correlated positively with CSF levels of total tau (T
      tau) (r = 0.44, P < 0.05) and phosphorylated tau protein (P-tau) (r = 0.50, P <
      0.01), but CSF activities of AChE or BuChE did not correlate with serum or CSF
      levels of 25OHD. CONCLUSIONS: In this pilot study, both CSF 25OHD level and CSF
      AChE activity were reduced in AD patients. However, the lack of correlations
      between 25OHD levels and CSF activities of AChE or BuChE might suggest different
      mechanisms of action, which could have implications for treatment trials.

PMID- 24312391
TI  - Pathotype and genetic diversity amongst Indian isolates of Xanthomonas oryzae pv.
      oryzae.
AB  - A number of rice resistance genes, called Xa genes, have been identified that
      confer resistance against various strains of Xanthomonas oryzae pv. oryzae (Xoo),
      the causal agent of bacterial blight. An understanding of pathotype diversity
      within the target pathogen population is required for identifying the Xa genes
      that are to be deployed for development of resistant rice cultivars. Among 1024
      isolates of Xoo collected from 20 different states of India, 11 major pathotypes
      were distinguished based on their reaction towards ten Xa genes (Xa1, Xa3, Xa4,
      xa5, Xa7, xa8, Xa10, Xa11, xa13, Xa21). Isolates belonging to pathotype III
      showing incompatible interaction towards xa8, xa13 and Xa21 and compatible
      interaction towards the rest of Xa genes formed the most frequent (41%) and
      widely distributed pathotype. The vast majority of the assayed Xoo isolates were
      incompatible with one or more Xa genes. Exceptionally, the isolates of pathotype
      XI were virulent on all Xa genes, but have restricted distribution. Considering
      the individual R-genes, Xa21 appeared as the most broadly effective, conferring
      resistance against 88 % of the isolates, followed in decreasing order by xa13 (84
      %), xa8 (64 %), xa5 (30 %), Xa7 (17 %) and Xa4 (14 %). Fifty isolates
      representing all the eleven pathotypes were analyzed by southern hybridization to
      determine their genetic relatedness using the IS1112 repeat element of Xoo.
      Isolates belonging to pathotype XI were the most divergent. The results suggest
      that one RFLP haplotype that is widely distributed all over India and is
      represented in strains from five different pathotypes might be an ancestral
      haplotype. A rice line with xa5, xa13 and Xa21 resistance genes is resistant to
      all strains, including those belonging to pathotype XI. This three gene
      combination appears to be the most suitable Xa gene combination to be deployed in
      Indian rice cultivars. 

PMID- 24312392
TI  - Skeletal correlates for body mass estimation in modern and fossil flying birds.
AB  - Scaling relationships between skeletal dimensions and body mass in extant birds
      are often used to estimate body mass in fossil crown-group birds, as well as in
      stem-group avialans. However, useful statistical measurements for constraining
      the precision and accuracy of fossil mass estimates are rarely provided, which
      prevents the quantification of robust upper and lower bound body mass estimates
      for fossils. Here, we generate thirteen body mass correlations and associated
      measures of statistical robustness using a sample of 863 extant flying birds. By
      providing robust body mass regressions with upper- and lower-bound prediction
      intervals for individual skeletal elements, we address the longstanding problem
      of body mass estimation for highly fragmentary fossil birds. We demonstrate that
      the most precise proxy for estimating body mass in the overall dataset, measured
      both as coefficient determination of ordinary least squares regression and
      percent prediction error, is the maximum diameter of the coracoid's humeral
      articulation facet (the glenoid). We further demonstrate that this result is
      consistent among the majority of investigated avian orders (10 out of 18). As a
      result, we suggest that, in the majority of cases, this proxy may provide the
      most accurate estimates of body mass for volant fossil birds. Additionally, by
      presenting statistical measurements of body mass prediction error for thirteen
      different body mass regressions, this study provides a much-needed quantitative
      framework for the accurate estimation of body mass and associated ecological
      correlates in fossil birds. The application of these regressions will enhance the
      precision and robustness of many mass-based inferences in future
      paleornithological studies. 

PMID- 24312393
TI  - The processing of symbolic and nonsymbolic ratios in school-age children.
AB  - This study tested the processing of ratios of natural numbers in school-age
      children. Nine- and eleven-year-olds were presented collections made up of orange
      and grey dots (i.e., nonsymbolic format) and fractions (i.e., symbolic format).
      They were asked to estimate ratios between the number of orange dots and the
      total number of dots and fractions by producing an equivalent ratio of surface
      areas (filling up a virtual glass). First, we tested whether symbolic notation of
      ratios affects their processing by directly comparing performance on fractions
      with that on dot sets. Second, we investigated whether children's estimates of
      nonsymbolic ratios of natural numbers relied at least in part on ratios of
      surface areas by contrasting a condition in which the ratio of surface areas
      occupied by dots covaried with the ratio of natural numbers and a condition in
      which this ratio of surface areas was kept constant across ratios of natural
      numbers. The results showed that symbolic notation did not really have a negative
      impact on performance among 9-year-olds, while it led to more accurate estimates
      in 11-year-olds. Furthermore, in dot conditions, children's estimates increased
      consistently with ratios between the number of orange dots and the total number
      of dots even when the ratio of surface areas was kept constant but were less
      accurate in that condition than when the ratio of surface areas covaried with the
      ratio of natural numbers. In summary, these results indicate that mental
      magnitude representation is more accurate when it is activated from symbolic
      ratios in children as young as 11 years old and that school-age children rely at
      least in part on ratios of surface areas to process nonsymbolic ratios of natural
      numbers when given the opportunity to do so. 

PMID- 24312394
TI  - Competitive interactions between parasitoids provide new insight into host
      suppression.
AB  - Understanding the dynamics of potential inter- and intraspecific competition in
      parasitoid communities is crucial in the screening of efficient parasitoid
      species and for utilization of the best parasitoid species combinations. In this
      respect, the host-parasitoid systems, Bemisia tabaci and two parasitoids,
      Eretmocerus hayati (exotic) and Encarsia sophia (existing) were studied under
      laboratory conditions to investigate whether interference competition between the
      exotic and existing species occurs as well as the influence of potential
      interference competition on the suppression of the host B. tabaci. Studies on
      interspecific-, intraspecific- and self-interference competition in two
      parasitoid species were conducted under both rich and limited host resource
      conditions. Results showed that (1) both parasitoid species negatively affect the
      progeny production of the other under both rich and limited host resource
      conditions; (2) both parasitoid species interfered intraspecifically on
      conspecific parasitized hosts when the available hosts are scarce and; 3) the
      mortality of B. tabaci induced by parasitoids via parasitism, host-feeding or
      both parasitism and host-feeding together varied among treatments under different
      host resource conditions, but showed promise for optimizing control strategies.
      As a result of our current findings, we suggest a need to investigate the
      interactions between the two parasitoids on continuous generations. 

PMID- 24312395
TI  - A lepidopteran-specific gene family encoding valine-rich midgut proteins.
AB  - Many lepidopteran larvae are serious agricultural pests due to their feeding
      activity. Digestion of the plant diet occurs mainly in the midgut and is
      facilitated by the peritrophic matrix (PM), an extracellular sac-like structure,
      which lines the midgut epithelium and creates different digestive compartments.
      The PM is attracting increasing attention to control lepidopteran pests by
      interfering with this vital function. To identify novel PM components and thus
      potential targets for insecticides, we performed an immunoscreening with anti-PM
      antibodies using an expression library representing the larval midgut
      transcriptome of the tobacco hornworm, Manduca sexta. We identified three cDNAs
      encoding valine-rich midgut proteins of M. sexta (MsVmps), which appear to be
      loosely associated with the PM. They are members of a lepidopteran-specific
      family of nine VMP genes, which are exclusively expressed in larval stages in M.
      sexta. Most of the MsVMP transcripts are detected in the posterior midgut, with
      the highest levels observed for MsVMP1. To obtain further insight into Vmp
      function, we expressed MsVMP1 in insect cells and purified the recombinant
      protein. Lectin staining and glycosidase treatment indicated that MsVmp1 is
      highly O-glycosylated. In line with results from qPCR, immunoblots revealed that
      MsVmp1 amounts are highest in feeding larvae, while MsVmp1 is undetectable in
      starving and molting larvae. Finally using immunocytochemistry, we demonstrated
      that MsVmp1 localizes to the cytosol of columnar cells, which secrete MsVmp1 into
      the ectoperitrophic space in feeding larvae. In starving and molting larvae,
      MsVmp1 is found in the gut lumen, suggesting that the PM has increased its
      permeability. The present study demonstrates that lepidopteran species including
      many agricultural pests have evolved a set of unique proteins that are not found
      in any other taxon and thus may reflect an important adaptation in the highly
      specialized lepidopteran digestive tract facing particular immune challenges. 

PMID- 24312396
TI  - Conformational polymorphism of m7GTP in crystal structure of the PB2 middle
      domain from human influenza A virus.
AB  - Influenza pandemics with human-to-human transmission of the virus are of great
      public concern. It is now recognized that a number of factors are necessary for
      human transmission and virulence, including several key mutations within the PB2
      subunit of RNA-dependent RNA polymerase. The structure of the middle domain in
      PB2 has been revealed with or without m(7)GTP, thus the middle domain is
      considered to be novel target for structure-based drug design. Here we report the
      crystal structure of the middle domain of H1N1 PB2 with or without m(7)GTP at 1.9
      A and 2.0 A resolution, respectively, which has two mutations (P453H, I471T) to
      increase electrostatic potential and solubility. Here we report the m(7)GTP has
      unique conformation differ from the reported structure. 7-methyl-guanine is fixed
      in the pocket, but particularly significant change is seen in ribose and
      triphosphate region: the buried 7-methyl-guanine indeed binds in the pocket
      forming by H357, F404, E361 and K376 but the triphosphate continues directly to
      the outer domain. The presented conformation of m(7)GTP may be a clue for the
      anti-influenza drug-design.

PMID- 24312397
TI  - Species-specific immunity induced by infection with Entamoeba histolytica and
      Entamoeba moshkovskii in mice.
AB  - Entamoeba histolytica, the parasitic amoeba responsible for amoebiasis, causes
      approximately 100,000 deaths every year. There is currently no vaccine against
      this parasite. We have previously shown that intracecal inoculation of E.
      histolytica trophozoites leads to chronic and non-healing cecitis in mice.
      Entamoeba moshkovskii, a closely related amoeba, also causes diarrhea and other
      intestinal disorders in this model. Here, we investigated the effect of infection
      followed by drug-cure of these species on the induction of immunity against
      homologous or heterologous species challenge. Mice were infected with E.
      histolytica or E. moshkovskii and treated with metronidazole 14 days later. Re
      challenge with E. histolytica or E. moshkovskii was conducted seven or 28 days
      following confirmation of the clearance of amoebae, and the degree of protection
      compared to non-exposed control mice was evaluated. We show that primary
      infection with these amoebae induces a species-specific immune response which
      protects against challenge with the homologous, but not a heterologous species.
      These findings pave the way, therefore, for the identification of novel amoebae
      antigens that may become the targets of vaccines and provide a useful platform to
      investigate host protective immunity to Entamoeba infections. 

PMID- 24312399
TI  - Storage/Turnover rate of inorganic carbon and its dissolvable part in the profile
      of saline/alkaline soils.
AB  - Soil inorganic carbon is the most common form of carbon in arid and semiarid
      regions, and has a very long turnover time. However, little is known about
      dissolved inorganic carbon storage and its turnover time in these soils. With 81
      soil samples taken from 6 profiles in the southern Gurbantongute Desert, China,
      we investigated the soil inorganic carbon (SIC) and the soil dissolved inorganic
      carbon (SDIC) in whole profiles of saline and alkaline soils by analyzing their
      contents and ages with radiocarbon dating. The results showed that there is
      considerable SDIC content in SIC, and the variations of SDIC and SIC contents in
      the saline soil profile were much larger than that in the alkaline profile. SDIC
      storage accounted for more than 20% of SIC storage, indicating that more than 1/5
      of the inorganic carbon in both saline and alkaline soil is not in non-leachable
      forms. Deep layer soil contains considerable inorganic carbon, with more than 80%
      of the soil carbon stored below 1 m, whether for SDIC or SIC. More importantly,
      SDIC ages were much younger than SIC in both saline soil and alkaline soil. The
      input rate of SDIC and SIC ranged from 7.58 to 29.54 g C m(-2) yr(-1) and 1.34 to
      5.33 g C m(-2) yr(-1) respectively for saline soil, and from 1.43 to 4.9 g C m(
      2) yr(-1) and 0.79 to 1.27 g C m(-2) yr(-1)respectively for alkaline soil. The
      comparison of SDIC and SIC residence time showed that using soil inorganic carbon
      to estimate soil carbon turnover would obscure an important fraction that
      contributes to the modern carbon cycle: namely the shorter residence and higher
      input rate of SDIC. This is especially true for SDIC in deep layers of the soil
      profile. 

PMID- 24312398
TI  - Smooth muscle LDL receptor-related protein-1 deletion induces aortic
      insufficiency and promotes vascular cardiomyopathy in mice.
AB  - Valvular disease is common in patients with Marfan syndrome and can lead to
      cardiomyopathy. However, some patients develop cardiomyopathy in the absence of
      hemodynamically significant valve dysfunction, suggesting alternative mechanisms
      of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1) in
      smooth muscle cells has been shown to cause vascular pathologies similar to
      Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and
      aortic aneurysms. This study used echocardiography and blood pressure monitoring
      in mouse models to determine whether inactivation of Lrp1 in vascular smooth
      muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence
      of valvular disease. Hemodynamic changes during treatment with captopril were
      also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice
      and progressed as they aged, whereas no significant aortic dilation was detected
      in wild type littermates. Diastolic blood pressure was lower and pulse pressure
      higher in Lrp1-knockout mice, which was normalized by treatment with captopril.
      Aortic dilation was followed by development of aortic insufficiency and
      subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle
      cell Lrp1 deficiency results in aortic dilation and insufficiency that causes
      secondary cardiomyopathy that can be improved by captopril. These findings
      provide novel insights into mechanisms of cardiomyopathy associated with vascular
      activation and offer a new model of valvular cardiomyopathy. 

PMID- 24312400
TI  - The changing integrin expression and a role for integrin beta8 in the
      chondrogenic differentiation of mesenchymal stem cells.
AB  - Many cartilage tissue engineering approaches aim to differentiate human
      mesenchymal stem cells (hMSCs) into chondrocytes and develop cartilage in vitro
      by targeting cell-matrix interactions. We sought to better inform the design of
      cartilage tissue engineering scaffolds by understanding how integrin expression
      changes during chondrogenic differentiation. In three models of in vitro
      chondrogenesis, we studied the temporal change of cartilage phenotype markers and
      integrin subunits during the differentiation of hMSCs. We found that transcript
      expression of most subunits was conserved across the chondrogenesis models, but
      was significantly affected by the time-course of differentiation. In particular,
      ITGB8 was up-regulated and its importance in chondrogenesis was further
      established by a knockdown of integrin beta8, which resulted in a non-hyaline
      cartilage phenotype, with no COL2A1 expression detected. In conclusion, we
      performed a systematic study of the temporal changes of integrin expression
      during chondrogenic differentiation in multiple chondrogenesis models, and
      revealed a role for integrin beta8 in chondrogenesis. This work enhances our
      understanding of the changing adhesion requirements of hMSCs during chondrogenic
      differentiation and underlines the importance of integrins in establishing a
      cartilage phenotype. 

PMID- 24312402
TI  - Do ecological niche model predictions reflect the adaptive landscape of species?:
      a test using Myristica malabarica Lam., an endemic tree in the Western Ghats,
      India.
AB  - Ecological niche models (ENM) have become a popular tool to define and predict
      the "ecological niche" of a species. An implicit assumption of the ENMs is that
      the predicted ecological niche of a species actually reflects the adaptive
      landscape of the species. Thus in sites predicted to be highly suitable, species
      would have maximum fitness compared to in sites predicted to be poorly suitable.
      As yet there are very few attempts to address this assumption. Here we evaluate
      this assumption. We used Bioclim (DIVA GIS version 7.3) and Maxent (version
      3.3.2) to predict the habitat suitability of Myristica malabarica Lam., an
      economically important tree occurring in the Western Ghats, India. We located
      populations of the trees naturally occurring in different habitat suitability
      regimes (from highly suitable to poorly suitable) and evaluated them for their
      regeneration ability and genetic diversity. We also evaluated them for two plant
      functional traits, fluctuating asymmetry--an index of genetic homeostasis, and
      specific leaf weight--an index of primary productivity, often assumed to be good
      surrogates of fitness. We show a significant positive correlation between the
      predicted habitat quality and plant functional traits, regeneration index and
      genetic diversity of populations. Populations at sites predicted to be highly
      suitable had a higher regeneration and gene diversity compared to populations in
      sites predicted to be poor or unsuitable. Further, individuals in the highly
      suitable sites exhibited significantly less fluctuating asymmetry and
      significantly higher specific leaf weight compared to individuals in the poorly
      suitable habitats. These results for the first time provide an explicit test of
      the ENM with respect to the plant functional traits, regeneration ability and
      genetic diversity of populations along a habitat suitability gradient. We discuss
      the implication of these results for designing viable species conservation and
      restoration programs.

PMID- 24312401
TI  - PKCepsilon signalling activates ERK1/2, and regulates aggrecan, ADAMTS5, and
      miR377 gene expression in human nucleus pulposus cells.
AB  - The protein kinase C (PKC) signaling, a major regulator of chondrocytic
      differentiation, has been also implicated in pathological extracellular matrix
      remodeling, and here we investigate the mechanism of PKCepsilon-dependent
      regulation of the chondrocytic phenotype in human nucleus pulposus (NP) cells
      derived from herniated disks. NP cells from each donor were successfully
      propagated for 25+ culture passages, with remarkable tolerance to repeated freeze
      and-thaw cycles throughout long-term culturing. More specifically, after an
      initial downregulation of COL2A1, a stable chondrocytic phenotype was attested by
      the levels of mRNA expression for aggrecan, biglycan, fibromodulin, and lumican,
      while higher expression of SOX-trio and Patched-1 witnessed further
      differentiation potential. NP cells in culture also exhibited a stable molecular
      profile of PKC isoforms: throughout patient samples and passages, mRNAs for PKC
      alpha, delta, epsilon, zeta, eta, iota, and u were steadily detected, whereas
      beta, gamma, and theta were not. Focusing on the signalling of PKCepsilon, an
      isoform that may confer protection against degeneration, we found that activation
      with the PKCepsilon-specific activator small peptide psiepsilonRACK led
      sequentially to a prolonged activation of ERK1/2, increased abundance of the
      early gene products ATF, CREB1, and Fos with concurrent silencing of
      transcription for Ki67, and increases in mRNA expression for aggrecan. More
      importantly, psiepsilonRACK induced upregulation of hsa-miR-377 expression,
      coupled to decreases in ADAMTS5 and cleaved aggrecan. Therefore, PKCepsilon
      activation in late passage NP cells may represent a molecular basis for aggrecan
      availability, as part of an PKCepsilon/ERK/CREB/AP-1-dependent transcriptional
      program that includes upregulation of both chondrogenic genes and microRNAs.
      Moreover, this pathway should be considered as a target for understanding the
      molecular mechanism of IVD degeneration and for therapeutic restoration of
      degenerated disks. 

PMID- 24312403
TI  - Heterogeneity and glycan masking of cell wall microstructures in the stems of
      Miscanthus x giganteus, and its parents M. sinensis and M. sacchariflorus.
AB  - Plant cell walls, being repositories of fixed carbon, are important sources of
      biomass and renewable energy. Miscanthus species are fast growing grasses with a
      high biomass yield and they have been identified as potential bioenergy crops.
      Miscanthus x giganteus is the sterile hybrid between M. sinensis and M.
      sacchariflorus, with a faster and taller growth than its parents. In this study,
      the occurrence of cell wall polysaccharides in stems of Miscanthus species has
      been determined using fluorescence imaging with sets of cell wall directed
      monoclonal antibodies. Heteroxylan and mixed linkage-glucan (MLG) epitopes are
      abundant in stem cell walls of Miscanthus species, but their distributions are
      different in relation to the interfascicular parenchyma and these epitopes also
      display different developmental dynamics. Detection of pectic homogalacturonan
      (HG) epitopes was often restricted to intercellular spaces of parenchyma regions
      and, notably, the high methyl ester LM20 HG epitope was specifically abundant in
      the pith parenchyma cell walls of M. x giganteus. Some cell wall probes cannot
      access their target glycan epitopes because of masking by other polysaccharides.
      In the case of Miscanthus stems, masking of xyloglucan by heteroxylan and masking
      of pectic galactan by heteroxylan and MLG was detected in certain cell wall
      regions. Knowledge of tissue level heterogeneity of polysaccharide distributions
      and molecular architectures in Miscanthus cell wall structures will be important
      for both understanding growth mechanisms and also for the development of
      potential strategies for the efficient deconstruction of Miscanthus biomass. 

PMID- 24312404
TI  - Proteomic interactions in the mouse vitreous-retina complex.
AB  - PURPOSE: Human vitreoretinal diseases are due to presumed abnormal mechanical
      interactions between the vitreous and retina, and translational models are
      limited. This study determined whether nonstructural proteins and potential
      retinal biomarkers were expressed by the normal mouse vitreous and retina.
      METHODS: Vitreous and retina samples from mice were collected by evisceration and
      analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins
      were further analyzed for differential expression and functional interactions
      using bioinformatic software. RESULTS: We identified 1,680 unique proteins in the
      retina and 675 unique proteins in the vitreous. Unbiased clustering identified
      protein pathways that distinguish retina from vitreous including oxidative
      phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous
      expressed oxidative stress and innate immunology pathways. Some intracellular
      protein pathways were found in both retina and vitreous, such as glycolysis and
      gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled
      between the retina and vitreous. We also identified human disease biomarkers
      represented in the mouse vitreous and retina, including carbonic anhydrase-2 and
      3, crystallins, macrophage inhibitory factor, glutathione peroxidase,
      peroxiredoxins, S100 precursors, and von Willebrand factor. CONCLUSIONS: Our
      analysis suggests the vitreous expresses nonstructural proteins that functionally
      interact with the retina to manage oxidative stress, immune reactions, and
      intracellular proteins may be exchanged between the retina and vitreous. This
      novel proteomic dataset can be used for investigating human vitreoretinopathies
      in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases
      will provide a critical tool for diagnostics and an avenue for therapeutics.

PMID- 24312405
TI  - Next generation sequencing of fecal DNA reveals the dietary diversity of the
      widespread insectivorous predator Daubenton's Bat (Myotis daubentonii) in
      Southwestern Finland.
AB  - Understanding predator-prey dynamics is a fundamental task in the evaluation of
      the adaptive capacities of species. However, direct observations or morphological
      identification of fecal remains do not offer an effective way to study the
      dietary ecology of elusive species, such as nocturnal insectivorous bats.
      However, recent advances in molecular techniques have opened a new method for
      identifying prey species from fecal samples. In this study, we amplified species
      specific mitochondrial COI fragments from fecal DNA extractions from 34
      individual Daubenton's bats (Myotis daubentonii) collected between 2008 and 2010
      from southwestern Finland. Altogether, 128 different species of prey were
      identified based on a comprehensive local DNA reference library. In our study
      area, Daubenton's bats feed most frequently on insects of the orders Diptera
      (found in the diet of 94% individuals), Trichoptera (69%) and Lepidoptera (63%).
      The most frequent dipteran family in the diet was Chironomidae, which was found
      in 31 of 34 individuals. Most common prey species were chironomids Microtendipes
      pedellus (found in 50% of bats), Glyptotendipes cauliginellus (44%), and
      Procladius ferrugineus (41%). For the first time, an accurate species level list
      of the diet of the insectivorous Daubenton's bat (Myotis daubentonii) in Finland
      is presented. We report a generally applicable method for describing the
      arthropod diet of vertebrate predators. We compare public databases to a national
      database to highlight the importance of a local reference database. 

PMID- 24312406
TI  - Functional Interactions between BM88/Cend1, Ran-binding protein M and Dyrk1B
      kinase affect cyclin D1 levels and cell cycle progression/exit in mouse
      neuroblastoma cells.
AB  - BM88/Cend1 is a neuronal-lineage specific modulator with a pivotal role in
      coordination of cell cycle exit and differentiation of neuronal precursors. In
      the current study we identified the signal transduction scaffolding protein Ran
      binding protein M (RanBPM) as a BM88/Cend1 binding partner and showed that
      BM88/Cend1, RanBPM and the dual specificity tyrosine-phosphorylation regulated
      kinase 1B (Dyrk1B) are expressed in mouse brain as well as in cultured embryonic
      cortical neurons while RanBPM can form complexes with either of the two other
      proteins. To elucidate a potential mechanism involving BM88/Cend1, RanBPM and
      Dyrk1B in cell cycle progression/exit, we transiently co-expressed these proteins
      in mouse neuroblastoma Neuro 2a cells. We found that the BM88/Cend1-dependent or
      Dyrk1B-dependent down-regulation of cyclin D1 is reversed following their
      functional interaction with RanBPM. More specifically, functional interaction of
      RanBPM with either BM88/Cend1 or Dyrk1B stabilizes cyclin D1 in the nucleus and
      promotes 5-bromo-2'-deoxyuridine (BrdU) incorporation as a measure of enhanced
      cell proliferation. However, the RanBPM-dependent Dyrk1B cytosolic retention and
      degradation is reverted in the presence of Cend1 resulting in cyclin D1
      destabilization. Co-expression of RanBPM with either BM88/Cend1 or Dyrk1B also
      had a negative effect on Neuro 2a cell differentiation. Our results suggest that
      functional interactions between BM88/Cend1, RanBPM and Dyrk1B affect the balance
      between cellular proliferation and differentiation in Neuro 2a cells and indicate
      that a potentially similar mechanism may influence cell cycle progression/exit
      and differentiation of neuronal precursors. 

PMID- 24312407
TI  - GPR35 activation reduces Ca2+ transients and contributes to the kynurenic acid
      dependent reduction of synaptic activity at CA3-CA1 synapses.
AB  - Limited information is available on the brain expression and role of GPR35, a
      Gi/o coupled receptor activated by kynurenic acid (KYNA). In mouse cultured
      astrocytes, we detected GPR35 transcript using RT-PCR and we found that KYNA (0.1
      to 100 uM) decreased forskolin (FRSK)-induced cAMP production (p<0.05). Both
      CID2745687 (3 uM, CID), a recently described GPR35 antagonist, and GPR35 gene
      silencing significantly prevented the action of KYNA on FRSK-induced cAMP
      production. In these cultures, we then evaluated whether GPR35 activation was
      able to modulate intracellular Ca(2+) concentration ([Ca(2+)]i ) and [Ca(2+)]i
      fluxes. We found that both KYNA and zaprinast, a phosphodiesterase (PDE)
      inhibitor and GPR35 agonist, did not modify either basal or peaks of [Ca(2+)]i
      induced by challenging the cells with ATP (30 uM). However, the [Ca(2+)]i plateau
      phase following peak was significantly attenuated by these compounds in a store
      operated Ca(2+) channel (SOC)-independent manner. The activation of GPR35 by KYNA
      and zaprinast was also studied at the CA3-CA1 synapse in the rat hippocampus.
      Evoked excitatory post synaptic currents (eEPSCs) were recorded from CA1
      pyramidal neurons in acute brain slices. The action of KYNA on GPR35 was
      pharmacologically isolated by using NMDA and alpha7 nicotinic receptor blockers
      and resulted in a significant reduction of eEPSC amplitude. This effect was
      prevented in the presence of CID. Moreover, zaprinast reduced eEPSC amplitude in
      a PDE5- and cGMP-independent mechanism, thus suggesting that glutamatergic
      transmission in this area is modulated by GPR35. In conclusion, GPR35 is
      expressed in cultured astrocytes and its activation modulates cAMP production and
      [Ca(2+)]i. GPR35 activation may contribute to KYNA effects on the previously
      reported decrease of brain extracellular glutamate levels and reduction of
      excitatory transmission. 

PMID- 24312408
TI  - The effect of automatic gain control structure and release time on cochlear
      implant speech intelligibility.
AB  - Nucleus cochlear implant systems incorporate a fast-acting front-end automatic
      gain control (AGC), sometimes called a compression limiter. The objective of the
      present study was to determine the effect of replacing the front-end compression
      limiter with a newly proposed envelope profile limiter. A secondary objective was
      to investigate the effect of AGC speed on cochlear implant speech
      intelligibility. The envelope profile limiter was located after the filter bank
      and reduced the gain when the largest of the filter bank envelopes exceeded the
      compression threshold. The compression threshold was set equal to the saturation
      level of the loudness growth function (i.e. the envelope level that mapped to the
      maximum comfortable current level), ensuring that no envelope clipping occurred.
      To preserve the spectral profile, the same gain was applied to all channels.
      Experiment 1 compared sentence recognition with the front-end limiter and with
      the envelope profile limiter, each with two release times (75 and 625 ms). Six
      implant recipients were tested in quiet and in four-talker babble noise, at a
      high presentation level of 89 dB SPL. Overall, release time had a larger effect
      than the AGC type. With both AGC types, speech intelligibility was lower for the
      75 ms release time than for the 625 ms release time. With the shorter release
      time, the envelope profile limiter provided higher group mean scores than the
      front-end limiter in quiet, but there was no significant difference in noise.
      Experiment 2 measured sentence recognition in noise as a function of presentation
      level, from 55 to 89 dB SPL. The envelope profile limiter with 625 ms release
      time yielded better scores than the front-end limiter with 75 ms release time. A
      take-home study showed no clear pattern of preferences. It is concluded that the
      envelope profile limiter is a feasible alternative to a front-end compression
      limiter. 

PMID- 24312409
TI  - Predicting plastid marker variation: can complete plastid genomes from closely
      related species help?
AB  - Rapidly evolving non-coding plastid regions (NCPs) are currently widely used in
      evolutionary biology especially in plant systematic studies where NCPs have
      become one of the most commonly used tools in clarifying species relationships.
      Currently, the generally small amount of sequence variation provided by NCPs
      compared to nuclear regions makes plastid phylogeny reconstruction challenging at
      the species-level, especially so in species rich clades such as Solanum with c.
      1,200 species. Previous studies have established that the set of most highly
      variable NCPs vary between major plant families, and here we explore whether this
      variation extends beyond family level to genera and major clades within genera.
      Using full plastome data, we identify the most highly variable plastid markers in
      the Potato clade of Solanum. We then compare sequence variation between the
      Potato and the closely related Morelloid clade. Results show that whilst a narrow
      set of NCPs show consistently high variation, levels of sequence variation in
      most NCPs differ greatly between the two closely related clades. The high
      variation detected between closely related groups implies that repeated screening
      studies will be needed for individual projects despite the potential availability
      of results from closely related taxa, and indicates a narrower applicability of
      family-specific screening studies than previously thought. 

PMID- 24312410
TI  - Putative panmixia in restricted populations of Trypanosoma cruzi isolated from
      wild Triatoma infestans in Bolivia.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, is subdivided into six
      discrete typing units (DTUs; TcI-TcVI) of which TcI is ubiquitous and genetically
      highly variable. While clonality is the dominant mode of propagation, recombinant
      events play a significant evolutive role. Recently, foci of wild Triatoma
      infestans have been described in Bolivia, mainly infected by TcI. Hence, for the
      first time, we evaluated the level of genetic exchange within TcI natural
      potentially panmictic populations (single DTU, host, area and sampling time).
      Seventy-nine TcI stocks from wild T. infestans, belonging to six populations were
      characterized at eight microsatellite loci. For each population, Hardy-Weinberg
      equilibrium (HWE), linkage disequilibrium (LD), and presence of repeated
      multilocus genotypes (MLG) were analyzed by using a total of seven statistics, to
      test the null hypothesis of panmixia (H0). For three populations, none of the
      seven statistics allowed to rejecting H0; for another one the low size did not
      allow us to conclude, and for the two others the tests have given contradictory
      results. Interestingly, apparent panmixia was only observed in very restricted
      areas, and was not observed when grouping populations distant of only two
      kilometers or more. Nevertheless it is worth stressing that for the statistic
      tests of "HWE", in order to minimize the type I error (i. e. incorrect rejection
      of a true H0), we used the Bonferroni correction (BC) known to considerably
      increase the type II error ( i. e. failure to reject a false H0). For the other
      tests (LD and MLG), we did not use BC and the risk of type II error in these
      cases was acceptable. Thus, these results should be considered as a good
      indicator of the existence of panmixia in wild environment but this must be
      confirmed on larger samples to reduce the risk of type II error. 

PMID- 24312411
TI  - Neural mechanisms underlying stop-and-restart difficulties: involvement of the
      motor and perceptual systems.
AB  - The ability to suddenly stop a planned movement or a movement being performed and
      restart it after a short interval is an important mechanism that allows
      appropriate behavior in response to contextual or environmental changes. However,
      performing such stop-and-restart movements smoothly is difficult at times. We
      investigated performance (response time) of stop-and-restart movements using a
      go/stop/re-go task and found consistent stop-and-restart difficulties after short
      (~100 ms) stop-to-restart intervals (SRSI), and an increased probability of
      difficulties after longer (>200 ms) SRSIs, suggesting that two different
      mechanisms underlie stop-and-restart difficulties. Next, we investigated motor
      evoked potentials (MEPs) in a moving muscle induced by transcranial magnetic
      stimulation during a go/stop/re-go task. In re-go trials with a short SRSI (100
      ms), the MEP amplitude continued to decrease after the re-go-signal onset,
      indicating that stop-and-restart difficulties with short SRSIs might be
      associated with a neural mechanism in the human motor system, namely, stop
      related suppression of corticomotor (CM) excitability. Finally, we recorded
      electroencephalogram (EEG) activity during a go/stop/re-go task and performed a
      single-trial-based EEG power and phase time-frequency analysis. Alpha-band EEG
      phase locking to re-go-signal, which was only observed in re-go trials with long
      SRSI (250 ms), weakened in the delayed re-go response trials. These EEG phase
      dynamics indicate an association between stop-and-restart difficulties with long
      SRSIs and a neural mechanism in the human perception system, namely, decreased
      probability of EEG phase locking to visual stimuli. In contrast, smooth stop-and
      restart human movement can be achieved in re-go trials with sufficient SRSI (150
      200 ms), because release of stop-related suppression and simultaneous counter
      activation of CM excitability may occur as a single task without second re-go
      signal perception. These results suggest that skilled motor behavior is subject
      to various constraints in not only motor, but also perceptual (and attentional),
      systems.

PMID- 24312412
TI  - Testing the reproducibility of multiple displacement amplification on genomes of
      clonal endosymbiont populations.
AB  - The multiple displacement amplification method has revolutionized genomic studies
      of uncultured bacteria, where the extraction of pure DNA in sufficient quantity
      for next-generation sequencing is challenging. However, the method is problematic
      in that it amplifies the target DNA unevenly, induces the formation of chimeric
      reads and also amplifies contaminating DNA. Here, we have tested the
      reproducibility of the multiple displacement amplification method using serial
      dilutions of extracted genomic DNA and intact cells from the cultured
      endosymbiont Bartonella australis. The amplified DNA was sequenced with the
      Illumina sequencing technology, and the results were compared to sequence data
      obtained from unamplified DNA in this study as well as from a previously
      published genome project. We show that artifacts such as the extent of the
      amplification bias, the percentage of chimeric reads and the relative fraction of
      contaminating DNA increase dramatically for the smallest amounts of template DNA.
      The pattern of read coverage was reproducibly obtained for samples with higher
      amounts of template DNA, suggesting that the bias is non-random and genome
      specific. A re-analysis of previously published sequence data obtained after
      amplification from clonal endosymbiont populations confirmed these predictions.
      We conclude that many of the artifacts associated with the use of the multiple
      displacement amplification method can be alleviated or much reduced by using
      multiple cells as the template for the amplification. These findings should be
      particularly useful for researchers studying the genomes of endosymbionts and
      other uncultured bacteria, for which a small clonal population of cells can be
      isolated. 

PMID- 24312413
TI  - Temporal learning and list-level proportion congruency: conflict adaptation or
      learning when to respond?
AB  - The current report presents a temporal learning account as a potential
      alternative to the conflict adaptation account of list-level proportion congruent
      effects in the Stroop paradigm. Specifically, retrieval of information about
      response times on previous trials influences a participant's preparedness to
      respond at a similar time on following trials. First, an adaptation of the
      Parallel Episodic Processing (PEP) model is presented, and a list-level effect is
      produced with a temporal learning mechanism. Next, linear mixed effect model
      analyses show that temporal learning biases are present in list-level proportion
      congruent data. A non-conflict experiment is then presented in which a list-level
      effect is observed with a contrast, rather than congruency, manipulation.
      Analyses of the experimental and simulated data could not, however, provide a
      clear picture of whether temporal learning was the sole contributor to the list
      level proportion congruent effect. These results do, however, demonstrate that
      caution is warranted when interpreting list-level proportion congruent effects. 

PMID- 24312414
TI  - Gene expression system in green sulfur bacteria by conjugative plasmid transfer.
AB  - Gene transfer and expression systems in green sulfur bacteria were established by
      bacterial conjugation with Escherichia coli. Conjugative plasmid transfer from E.
      coli S17-1 to a thermophilic green sulfur bacterium, Chlorobaculum tepidum
      (formerly Chlorobium tepidum) WT2321, was executed with RSF1010-derivative broad
      host-range plasmids, named pDSK5191 and pDSK5192, that confer erythromycin and
      streptomycin/spectinomycin resistance, respectively. The transconjugants
      harboring these plasmids were reproducibly obtained at a frequency of
      approximately 10(-5) by selection with erythromycin and a combination of
      streptomycin and spectinomycin, respectively. These plasmids were stably
      maintained in C. tepidum cells in the presence of these antibiotics. The plasmid
      transfer to another mesophilic green sulfur bacterium, C. limnaeum (formerly
      Chlorobium phaeobacteroides) RK-j-1, was also achieved with pDSK5192. The
      expression plasmid based on pDSK5191 was constructed by incorporating the
      upstream and downstream regions of the pscAB gene cluster on the C. tepidum
      genome, since these regions were considered to include a constitutive promoter
      and a rho-independent terminator, respectively. Growth defections of the ?cycA
      and ?soxB mutants were completely rescued after introduction of pDSK5191-cycA and
      -soxB that were designed to express their complementary genes. On the other hand,
      pDSK5191-6xhis-pscAB, which incorporated the gene cluster of 6xhis-pscA and pscB,
      produced approximately four times more of the photosynthetic reaction center
      complex with His-tagged PscA as compared with that expressed in the genome by the
      conventional natural transformation method. This expression system, based on
      conjugative plasmid, would be applicable to general molecular biological studies
      of green sulfur bacteria. 

PMID- 24312415
TI  - Branched chain amino acid suppresses hepatocellular cancer stem cells through the
      activation of mammalian target of rapamycin.
AB  - Differentiation of cancer stem cells (CSCs) into cancer cells causes increased
      sensitivity to chemotherapeutic agents. Although inhibition of mammalian target
      of rapamycin (mTOR) leads to CSC survival, the effect of branched chain amino
      acids (BCAAs), an mTOR complex 1 (mTORC1) activator remains unknown. In this
      study, we examined the effects of BCAA on hepatocellular carcinoma (HCC) cells
      expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5
      fluorouracil (FU) on expression of EpCAM and other CSC-related markers, as well
      as cell proliferation in HCC cells and in a xenograft mouse model. We also
      characterized CSC-related and mTOR signal-related molecule expression and
      tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression
      of constitutively active rheb (caRheb). mTOR signal-related molecule expression
      was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency
      of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect
      of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU
      alone in the xenograft model. Stimulation with high doses of BCAA activated
      mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR
      complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and
      little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by
      reducing the population of cscs via the mTOR pathway. This result suggests the
      utility of BCAA in liver cancer therapy. 

PMID- 24312416
TI  - Role of the APOE epsilon2/epsilon3/epsilon4 polymorphism in the development of
      primary open-angle glaucoma: evidence from a comprehensive meta-analysis.
AB  - Primary open-angle glaucoma (POAG) is one of the leading causes of blindness
      worldwide. The association between the APOE epsilon2/epsilon3/epsilon4
      polymorphism and the risk of POAG has been widely reported, but the results of
      previous studies remain controversial. To comprehensively evaluate the APOE
      epsilon2/epsilon3/epsilon4 polymorphism on the genetic risk for POAG, we
      performed a systematic review and meta-analysis of previously published studies.
      The PubMed and Web of Science databases were systematically searched to identify
      relevant studies. Data were extracted from these studies and odds ratios with
      corresponding 95% confidence intervals were computed to estimate the strength of
      the association. Stratified analyses according to ethnicity and sensitivity
      analyses were also conducted for further confirmation. A total of nine studies
      were eligible for the meta-analysis, and these studies included data on 1928 POAG
      cases and 1793 unrelated match controls. The combined results showed that there
      were no associations between the APOE epsilon2/epsilon3/epsilon4 polymorphism and
      POAG risk in any of the 10 comparison models. The analysis that was stratified by
      ethnicity subgroups also failed to reveal a significant association. The
      sensitivity analysis confirmed the stability and reliability of the findings.
      There was no risk of publication bias. Our meta-analysis provides strong evidence
      that the APOE epsilon2/epsilon3/epsilon4 polymorphism is not associated with POAG
      susceptibility in any populations.

PMID- 24312417
TI  - Dopaminergic regulation of circadian food anticipatory activity rhythms in the
      rat.
AB  - Circadian activity rhythms are jointly controlled by a master pacemaker in the
      hypothalamic suprachiasmatic nuclei (SCN) and by food-entrainable circadian
      oscillators (FEOs) located elsewhere. The SCN mediates synchrony to daily light
      dark cycles, whereas FEOs generate activity rhythms synchronized with regular
      daily mealtimes. The location of FEOs generating food anticipation rhythms, and
      the pathways that entrain these FEOs, remain to be clarified. To gain insight
      into entrainment pathways, we developed a protocol for measuring phase shifts of
      anticipatory activity rhythms in response to pharmacological probes. We used this
      protocol to examine a role for dopamine signaling in the timing of circadian food
      anticipation. To generate a stable food anticipation rhythm, rats were fed 3h/day
      beginning 6-h after lights-on or in constant light for at least 3 weeks. Rats
      then received the D2 agonist quinpirole (1 mg/kg IP) alone or after pretreatment
      with the dopamine synthesis inhibitor alpha-methylparatyrosine (AMPT). By
      comparison with vehicle injections, quinpirole administered 1-h before lights-off
      (19h before mealtime) induced a phase delay of activity onset prior to the next
      meal. Delay shifts were larger in rats pretreated with AMPT, and smaller
      following quinpirole administered 4-h after lights-on. A significant shift was
      not observed in response to the D1 agonist SKF81297. These results provide
      evidence that signaling at D2 receptors is involved in phase control of FEOs
      responsible for circadian food anticipatory rhythms in rats. 

PMID- 24312418
TI  - Measurement of biomolecular diffusion in extracellular matrix condensed by
      fibroblasts using fluorescence correlation spectroscopy.
AB  - The extracellular matrix (ECM) comprises the heterogeneous environment outside of
      cells in a biological system. The ECM is dynamically organized and regulated, and
      many biomolecules secreted from cells diffuse throughout the ECM, regulating a
      variety of cellular processes. Therefore, investigation of the diffusive
      behaviors of biomolecules in the extracellular environment is critical. In this
      study, we investigated the diffusion coefficients of biomolecules of various
      sizes, measuring from 1 to 10 nm in radius, by fluorescence correlation
      spectroscopy in contracted collagen gel caused by fibroblasts, a traditional
      culture model of dynamic rearrangement of collagen fibers. The diffusion
      coefficients of the biomolecules in control collagen gel without cells decreased
      slightly as compared to those in solution, while the diffusion coefficients of
      biomolecules in the contracted gel at the cell vicinity decreased dramatically.
      Additionally, the diffusion coefficients of biomolecules were inversely
      correlated with molecular radius. In collagen gels populated with fibroblasts,
      the diffusion coefficient at the cell vicinity clearly decreased in the first 24
      h of culture. Furthermore, molecular diffusion was greatly restricted, with a
      central focus on the populated cells. By using the obtained diffusion
      coefficients of biomolecules, we calculated the collagen fiber condensation ratio
      by fibroblasts in the cell vicinity at 3 days of culture to represent a 52-fold
      concentration. Thus, biomolecular diffusion is restricted in the vicinity of the
      cells where collagen fibers are highly condensed. 

PMID- 24312419
TI  - Genome-wide microsatellite identification in the fungus Anisogramma anomala using
      Illumina sequencing and genome assembly.
AB  - High-throughput sequencing has been dramatically accelerating the discovery of
      microsatellite markers (also known as Simple Sequence Repeats). Both 454 and
      Illumina reads have been used directly in microsatellite discovery and primer
      design (the "Seq-to-SSR" approach). However, constraints of this approach
      include: 1) many microsatellite-containing reads do not have sufficient flanking
      sequences to allow primer design, and 2) difficulties in removing microsatellite
      loci residing in longer, repetitive regions. In the current study, we applied the
      novel "Seq-Assembly-SSR" approach to overcome these constraints in Anisogramma
      anomala. In our approach, Illumina reads were first assembled into a draft
      genome, and the latter was then used in microsatellite discovery. A. anomala is
      an obligate biotrophic ascomycete that causes eastern filbert blight disease of
      commercial European hazelnut. Little is known about its population structure or
      diversity. Approximately 26 M 146 bp Illumina reads were generated from a paired
      end library of a fungal strain from Oregon. The reads were assembled into a draft
      genome of 333 Mb (excluding gaps), with contig N50 of 10,384 bp and scaffold N50
      of 32,987 bp. A bioinformatics pipeline identified 46,677 microsatellite motifs
      at 44,247 loci, including 2,430 compound loci. Primers were successfully designed
      for 42,923 loci (97%). After removing 2,886 loci close to assembly gaps and 676
      loci in repetitive regions, a genome-wide microsatellite database of 39,361 loci
      was generated for the fungus. In experimental screening of 236 loci using four
      geographically representative strains, 228 (96.6%) were successfully amplified
      and 214 (90.7%) produced single PCR products. Twenty-three (9.7%) were found to
      be perfect polymorphic loci. A small-scale population study using 11 polymorphic
      loci revealed considerable gene diversity. Clustering analysis grouped isolates
      of this fungus into two clades in accordance with their geographic origins. Thus,
      the "Seq-Assembly-SSR" approach has proven to be a successful one for
      microsatellite discovery. 

PMID- 24312420
TI  - Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of
      genetic skeletal diseases.
AB  - Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are skeletal
      disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are
      characterised by short-limbed dwarfism and premature osteoarthritis.
      Interestingly, recent reports suggest patients can also manifest with muscle
      weakness. Here we present a detailed analysis of two mouse models of the
      PSACH/MED disease spectrum; DeltaD469 T3-COMP (PSACH) and V194D matrilin-3 (MED).
      In grip test experiments T3-COMP mice were weaker than wild-type littermates,
      whereas V194D mice behaved as controls, confirming that short-limbed dwarfism
      alone does not contribute to PSACH/MED-related muscle weakness. Muscles from T3
      COMP mice showed an increase in centronuclear fibers at the myotendinous
      junction. T3-COMP tendons became more lax in cyclic testing and showed thicker
      collagen fibers when compared with wild-type tissue; matrilin-3 mutant tissues
      were indistinguishable from controls. This comprehensive study of the myopathy
      associated with PSACH/MED mutations enables a better understanding of the disease
      progression, confirms that it is genotype specific and that the limb weakness
      originates from muscle and tendon pathology rather than short-limbed dwarfism
      itself. Since some patients are primarily diagnosed with neuromuscular symptoms,
      this study will facilitate better awareness of the differential diagnoses that
      might be associated with the PSACH/MED spectrum and subsequent care of PSACH/MED
      patients. 

PMID- 24312421
TI  - Reprogramming of various cell types to a beta-like state by Pdx1, Ngn3 and MafA.
AB  - The three transcription factors, PDX1, NGN3 and MAFA, are very important in
      pancreatic development. Overexpression of these three factors can reprogram both
      pancreatic exocrine cells and SOX9-positive cells of the liver into cells
      resembling pancreatic beta cells. In this study we investigate whether other cell
      types can be reprogrammed. Eight cell types are compared and the results are
      consistent with the idea that reprogramming occurs to a greater degree for
      developmentally related cells (pancreas, liver) than for other types, such as
      fibroblasts. Using a line of mouse hepatocyte-derived cells we screened 13
      compounds for the ability to increase the yield of reprogrammed cells. Three are
      active and when used in combination they can increase the yield of insulin
      immunopositive cells by a factor of six. These results should contribute to the
      eventual ability to develop a new cure for diabetes based on the ability to
      reprogram other cells in the body to a beta cell phenotype. 

PMID- 24312422
TI  - Fyn-dependent gene networks in acute ethanol sensitivity.
AB  - Studies in humans and animal models document that acute behavioral responses to
      ethanol are predisposing factor for the risk of long-term drinking behavior.
      Prior microarray data from our laboratory document strain- and brain region
      specific variation in gene expression profile responses to acute ethanol that may
      be underlying regulators of ethanol behavioral phenotypes. The non-receptor
      tyrosine kinase Fyn has previously been mechanistically implicated in the
      sedative-hypnotic response to acute ethanol. To further understand how Fyn may
      modulate ethanol behaviors, we used whole-genome expression profiling. We
      characterized basal and acute ethanol-evoked (3 g/kg) gene expression patterns in
      nucleus accumbens (NAC), prefrontal cortex (PFC), and ventral midbrain (VMB) of
      control and Fyn knockout mice. Bioinformatics analysis identified a set of Fyn
      related gene networks differently regulated by acute ethanol across the three
      brain regions. In particular, our analysis suggested a coordinate basal decrease
      in myelin-associated gene expression within NAC and PFC as an underlying factor
      in sensitivity of Fyn null animals to ethanol sedation. An in silico analysis
      across the BXD recombinant inbred (RI) strains of mice identified a significant
      correlation between Fyn expression and a previously published ethanol loss-of
      righting-reflex (LORR) phenotype. By combining PFC gene expression correlates to
      Fyn and LORR across multiple genomic datasets, we identified robust Fyn-centric
      gene networks related to LORR. Our results thus suggest that multiple system-wide
      changes exist within specific brain regions of Fyn knockout mice, and that
      distinct Fyn-dependent expression networks within PFC may be important
      determinates of the LORR due to acute ethanol. These results add to the
      interpretation of acute ethanol behavioral sensitivity in Fyn kinase null
      animals, and identify Fyn-centric gene networks influencing variance in ethanol
      LORR. Such networks may also inform future design of pharmacotherapies for the
      treatment and prevention of alcohol use disorders. 

PMID- 24312423
TI  - Effect of 2-chloro-substitution of adenine moiety in mixed-ligand gold(I)
      triphenylphosphine complexes on anti-inflammatory activity: the discrepancy
      between the in vivo and in vitro models.
AB  - A series of gold(I) triphenylphosphine (PPh3) complexes (1-9) involving 2-chloro
      N6-(substituted-benzyl)adenine derivatives as N-donor ligands was synthesized and
      thoroughly characterized by relevant methods, including electrospray-ionization
      (ESI) mass spectrometry and multinuclear NMR spectroscopy. The anti-inflammatory
      and antiedematous effects of three representatives 1, 5 and 9 were evaluated by
      means of in vitro model based on the expression of pro- and anti-inflammatory
      cytokines and influence of the complexes on selected forms of matrix
      metalloproteinases secreted by LPS-activated THP-1 monocytes and in vivo model
      evaluating the antiedematous effect of the complexes in the carrageenan-induced
      rat hind-paw edema model. In addition to the pharmacological observations, the
      affected hind paws were post mortem subjected to histological and
      immunohistochemical evaluations. The results of both in vivo and ex vivo methods
      revealed low antiedematous and anti-inflammatory effects of the complexes, even
      though the in vitro model identified them as promising anti-inflammatory acting
      compounds. The reason for this discrepancy lies probably in low stability of the
      studied complexes in biological environment, as demonstrated by the solution
      interaction studies with sulfur-containing biomolecules (cysteine and reduced
      glutathione) using the ESI mass spectrometry. 

PMID- 24312424
TI  - Isolation and functional characterization of calcitonin-like diuretic hormone
      receptors in Rhodnius prolixus.
AB  - Several families of diuretic hormones exist in insects, one of which is the
      calcitonin-like diuretic hormone (CT/DH) family. CT/DH mediates its effects by
      binding to family B G-protein coupled receptors (GPCRs). Here we isolate and
      functionally characterize two R. prolixusCT/DH receptor paralogs (Rhopr-CT/DH-R1
      and Rhopr-CT/DH-R2) using a novel heterologous assay utilizing a modified human
      embryonic kidney 293 (HEK293) cell line. Rhopr-CT/DH-R1 is orthologous to the
      previously characterized D. melanogasterCT/DH receptor (CG17415) while Rhopr
      CT/DH-R2 is orthologous to the D. melanogaster receptor (CG4395), an orphan
      receptor whose ligand was unknown until now. We determine the cDNA sequences of
      three splice variants encoding Rhopr-CT/DH-R1 (Rhopr-CT/DH-R1-A, Rhopr-CT/DH-R1-B
      and Rhopr-CT/DH-R1-C) and two splice variants encoding Rhopr-CT/DH-R2 (Rhopr
      CT/DH-R2-A and Rhopr-CT/DH-R2-B). Rhopr-CT/DH-R1-A and Rhopr-CT/DH-R2-A encode
      truncated receptors that lack six and seven of the characteristic seven
      transmembrane domains, respectively. Rhopr-CT/DH-R1-B and Rhopr-CT/DH-R1-C, which
      only differ by 2 amino acids in their C-terminal domain, can both be activated by
      Rhopr-CT/DH at equal sensitivities (EC50 = 200-300 nM). Interestingly, Rhopr
      CT/DH-R2-B is much more sensitive to Rhopr-CT/DH (EC50 = 15 nM) compared to Rhopr
      CT/DH-R1-B/C and also yields a much greater response (amplitude) in our
      heterologous assay. This is the first study to reveal that insects possess at
      least two CT/DH receptors, which may be functionally different. Quantitative PCR
      demonstrates that Rhopr-CT/DH-R1 and Rhopr-CT/DH-R2 have distinct expression
      patterns, with both receptors expressed centrally and peripherally. Moreover, the
      expression analysis also identified novel target tissues for this neuropeptide,
      including testes, ovaries and prothoracic glands, suggesting a possible role for
      Rhopr-CT/DH in reproductive physiology and development.

PMID- 24312425
TI  - Exaggerated trait allometry, compensation and trade-offs in the New Zealand
      giraffe weevil (Lasiorhynchus barbicornis).
AB  - Sexual selection has driven the evolution of exaggerated traits among diverse
      animal taxa. The production of exaggerated traits can come at a cost to other
      traits through trade-offs when resources allocated to trait development are
      limited. Alternatively some traits can be selected for in parallel to support or
      compensate for the cost of bearing the exaggerated trait. Male giraffe weevils
      (Lasiorhynchus barbicornis) display an extremely elongated rostrum used as a
      weapon during contests for mates. Here we characterise the scaling relationship
      between rostrum and body size and show that males have a steep positive
      allometry, but that the slope is non-linear due to a relative reduction in
      rostrum length for the largest males, suggesting a limitation in resource
      allocation or a diminishing requirement for large males to invest increasingly
      into larger rostra. We also measured testes, wings, antennae, fore- and hind
      tibia size and found no evidence of a trade-off between these traits and rostrum
      length when comparing phenotypic correlations. However, the relative length of
      wings, antennae, fore- and hind-tibia all increased with relative rostrum length
      suggesting these traits may be under correlational selection. Increased
      investment in wing and leg length is therefore likely to compensate for the costs
      of flying with, and wielding the exaggerated rostrum of larger male giraffe
      weevils. These results provide a first step in identifying the potential for
      trait compensation and trades-offs, but are phenotypic correlations only and
      should be interpreted with care in the absence of breeding experiments. 

PMID- 24312426
TI  - Gene expression profiles resulting from stable loss of p53 mirrors its role in
      tissue differentiation.
AB  - The tumor suppressor gene p53 is involved in a variety of cellular activities
      such as cellular stress responses, cell cycle regulation and differentiation. In
      our previous studies we have shown p53's transcription activating role to be
      important in osteoblast differentiation. There is still a debate in the
      literature as to whether p53 inhibits or promotes differentiation. We have found
      p53 heterozygous mice to show a p53 dependency on some bone marker gene
      expression that is absent in knockout mice. Mice heterozygous for p53 also show a
      higher incidence of osteosarcomas than p53 knockout mice. This suggests that p53
      is able to modify the environment within osteoblasts. In this study we compare
      changes in gene expression resulting after either a transient or stable reduction
      in p53. Accordingly we reduced p53 levels transiently and stably in C2C12 cells,
      which are capable of both myoblast and osteoblast differentiation, and compared
      the changes in gene expression of candidate genes regulated by the p53 pathway.
      Using a PCR array to assay for p53 target genes, we have found different
      expression profiles when comparing stable versus transient knockdown of p53. As
      expected, several genes with profound changes after transient p53 loss were
      related to apoptosis and cell cycle regulation. In contrast, stable p53 loss
      produced a greater change in MyoD and other transcription factors with tissue
      specific roles, suggesting that long term loss of p53 affects tissue homeostasis
      to a greater degree than changes resulting from acute loss of p53. These
      differences in gene expression were validated by measuring promoter activity of
      different pathway specific genes involved in differentiation. These studies
      suggest that an important role for p53 is context dependent, with a stable
      reduction in p53 expression affecting normal tissue physiology more than acute
      loss of p53. 

PMID- 24312427
TI  - Sensitization potential of dental resins: 2-hydroxyethyl methacrylate and its
      water-soluble oligomers have immunostimulatory effects.
AB  - The immunostimulatory effects of the representative dental resin monomer 2
      hydroxyethyl methacrylate (HEMA), a HEMA derivative that does not contain a
      double bond (2-hydroxyethyl isobutyrate, HEIB), and polymerized water-soluble
      oligomers of HEMA (PHEMA) were investigated. It is known that expression levels
      of either or both of CD54 and CD86 in THP-1 cells are increased by exposure to
      sensitizing substances. In this study, the expression levels of CD54 and CD86,
      the production of reactive oxygen species (ROS), and the viability of the cells
      were measured after 24 h of incubation with these materials at different
      concentrations. The concentrations of the materials that induced the expression
      of both CD54 and CD86 were low in the following order: NiSO4, HEMA, and methyl
      methacrylate (MMA). These results indicate that these dental resin monomers have
      lower sensitizing potentials than NiSO4. Although HEIB, which lacks a double
      bond, resulted in negligible ROS production and reduced cytotoxicity than HEMA,
      it induced the expression of CD54 and CD86. Comparison of the results for HEMA
      and HEIB indicates that dental resin monomer-induced sensitization may be related
      not only to the oxidative stress related to the methacryloyl group but also to
      the structures of these compounds. Of particular interest is the result that a
      water-soluble PHEMA oligomer with a relatively high-molecular weight also
      exhibited negligible cytotoxicity, whereas the expression level of CD54 increased
      after exposure to PHEMA at a high concentration. This result serves as a warning
      that polymerized substances also have the potential to induce sensitization. This
      study provides insight into the nature of allergic responses to dental resin
      materials in clinical use and may facilitate the development of more
      biocompatible restorative materials in the future. 

PMID- 24312428
TI  - Biopterin metabolism and eNOS expression during hypoxic pulmonary hypertension in
      mice.
AB  - Tetrahydrobiopterin (BH4), which fosters the formation of and stabilizes
      endothelial NO synthase (eNOS) as an active dimer, tightly regulates eNOS
      coupling / uncoupling. Moreover, studies conducted in genetically-modified models
      demonstrate that BH4 pulmonary deficiency is a key determinant in the
      pathogenesis of pulmonary hypertension. The present study thus investigates
      biopterin metabolism and eNOS expression, as well as the effect of sepiapterin (a
      precursor of BH4) and eNOS gene deletion, in a mice model of hypoxic pulmonary
      hypertension. In lungs, chronic hypoxia increased BH4 levels and eNOS expression,
      without modifying dihydrobiopterin (BH2, the oxidation product of BH4) levels,
      GTP cyclohydrolase-1 or dihydrofolate reductase expression (two key enzymes
      regulating BH4 availability). In intrapulmonary arteries, chronic hypoxia also
      increased expression of eNOS, but did not induce destabilisation of eNOS dimers
      into monomers. In hypoxic mice, sepiapterin prevented increase in right
      ventricular systolic pressure and right ventricular hypertrophy, whereas it
      modified neither remodelling nor alteration in vasomotor responses (hyper
      responsiveness to phenylephrine, decrease in endothelium-dependent relaxation to
      acetylcholine) in intrapulmonary arteries. Finally, deletion of eNOS gene
      partially prevented hypoxia-induced increase in right ventricular systolic
      pressure, right ventricular hypertrophy and remodelling of intrapulmonary
      arteries. Collectively, these data demonstrate the absence of BH4/BH2 changes and
      eNOS dimer destabilisation, which may induce eNOS uncoupling during hypoxia
      induced pulmonary hypertension. Thus, even though eNOS gene deletion and
      sepiapterin treatment exert protective effects on hypoxia-induced pulmonary
      vascular remodelling, increase on right ventricular pressure and / or right
      ventricular hypertrophy, these effects appear unrelated to biopterin-dependent
      eNOS uncoupling within pulmonary vasculature of hypoxic wild-type mice. 

PMID- 24312429
TI  - Characterization of a small auxin-up RNA (SAUR)-like gene involved in Arabidopsis
      thaliana development.
AB  - The root of Arabidopsis thaliana is used as a model system to unravel the
      molecular nature of cell elongation and its arrest. From a micro-array performed
      on roots that were treated with aminocyclopropane-1-carboxylic acid (ACC), the
      precursor of ethylene, a Small auxin-up RNA (SAUR)-like gene was found to be up
      regulated. As it appeared as the 76th gene in the family, it was named SAUR76.
      Root and leaf growth of overexpression lines ectopically expressing SAUR76
      indicated the possible involvement of the gene in the division process. Using
      promoter::GUS and GFP lines strong expression was seen in endodermal and
      pericycle cells at the end of the elongation zone and during several stages of
      lateral root primordia development. ACC and IAA/NAA were able to induce a strong
      up regulation of the gene and changed the expression towards cortical and even
      epidermal cells at the beginning of the elongation zone. Confirmation of this up
      regulation of expression was delivered using qPCR, which also indicated that the
      expression quickly returned to normal levels when the inducing IAA-stimulus was
      removed, a behaviour also seen in other SAUR genes. Furthermore, confocal
      analysis of protein-GFP fusions localized the protein in the nucleus, cytoplasm
      and plasma membrane. SAUR76 expression was quantified in several mutants in
      ethylene and auxin-related pathways, which led to the conclusion that the
      expression of SAUR76 is mainly regulated by the increase in auxin that results
      from the addition of ACC, rather than by ACC itself. 

PMID- 24312430
TI  - Herbivory in spiders: the importance of pollen for orb-weavers.
AB  - Orb-weaving spiders (Araneidae) are commonly regarded as generalist insect
      predators but resources provided by plants such as pollen may be an important
      dietary supplementation. Their webs snare insect prey, but can also trap aerial
      plankton like pollen and fungal spores. When recycling their orb webs, the
      spiders may therefore also feed on adhering pollen grains or fungal spores via
      extraoral digestion. In this study we measured stable isotope ratios in the
      bodies of two araneid species (Aculepeira ceropegia and Araneus diadematus),
      their potential prey and pollen to determine the relative contribution of pollen
      to their diet. We found that about 25% of juvenile orb-weaving spiders' diet
      consisted of pollen, the other 75% of flying insects, mainly small dipterans and
      hymenopterans. The pollen grains in our study were too large to be taken up
      accidentally by the spiders and had first to be digested extraorally by enzymes
      in an active act of consumption. Therefore, pollen can be seen as a substantial
      component of the spiders' diet. This finding suggests that these spiders need to
      be classified as omnivores rather than pure carnivores. 

PMID- 24312431
TI  - alpha-Synuclein oligomers induced by docosahexaenoic acid affect membrane
      integrity.
AB  - A key feature of Parkinson disease is the aggregation of alpha-synuclein and its
      intracellular deposition in fibrillar form. Increasing evidence suggests that the
      pathogenicity of alpha-synuclein is correlated with the activity of oligomers
      formed in the early stages of its aggregation process. Oligomers toxicity seems
      to be associated with both their ability to bind and affect the integrity of
      lipid membranes. Previously, we demonstrated that alpha-synuclein forms
      oligomeric species in the presence of docosahexaenoic acid and that these species
      are toxic to cells. Here we studied how interaction of these oligomers with
      membranes results in cell toxicity, using cellular membrane-mimetic and cell
      model systems. We found that alpha-synuclein oligomers are able to interact with
      large and small unilamellar negatively charged vesicles acquiring an increased
      amount of alpha-helical structure, which induces small molecules release. We
      explored the possibility that oligomers effects on membranes could be due to pore
      formation, to a detergent-like effect or to fibril growth on the membrane. Our
      biophysical and cellular findings are consistent with a model where alpha
      synuclein oligomers are embedded into the lipid bilayer causing transient
      alteration of membrane permeability. 

PMID- 24312432
TI  - Introduced goldfish affect amphibians through inhibition of sexual behaviour in
      risky habitats: an experimental approach.
AB  - The introduction of alien species is one of the major causes of current and
      global biodiversity loss. The introduction of fish can be a particular threat to
      native amphibian populations, which are declining worldwide. One way for
      amphibians to persist in such altered environments is to adopt anti-predator
      strategies especially at the behavioural level. However, although it has been
      shown that avoidance behaviour may decrease the probability of being detected by
      a potential predator, little is known on the consequences on sexual behaviour. In
      this study, we tested the hypothesis that adult Alpine newts (Ichthyosaura
      alpestris) use shelters more often and exhibit less sexual activity in the
      presence of goldfish (Carassius auratus) and that they reduce sexual activity
      more in risky micro-habitats than in safe environments. To this end, we assessed
      behavioural patterns of adult newts in a replicated laboratory design. Goldfish
      were present in direct contact with newts in half of the tanks. Consistently
      throughout the study period, significantly more newts used shelter in the
      presence of fish than in their absence. Newts also significantly decreased their
      sexual activity level overall, but specially outside the shelter when they were
      in direct contact with fish. These results show that fish presence can affect
      newts in complex ways, such as through inhibition of their reproduction. Our work
      highlights that integrating behaviour in conservation studies is essential to
      understanding the patterns of coexistence and exclusion between introduced fish
      and amphibians. 

PMID- 24312433
TI  - Neonatal brain metabolite concentrations: an in vivo magnetic resonance
      spectroscopy study with a clinical MR system at 3 Tesla.
AB  - Brain metabolite concentrations change dynamically throughout development,
      especially during early childhood. The purpose of this study was to investigate
      the brain metabolite concentrations of neonates (postconceptional age (PCA): 30
      to 43 weeks) using single-voxel magnetic resonance spectroscopy (MRS) and to
      discuss the relationships between the changes in the concentrations of such
      metabolites and brain development during the neonatal period. A total of 83
      neonatal subjects were included using the following criteria: the neonates had to
      be free of radiological abnormalities, organic illness, and neurological
      symptoms; the MR spectra had to have signal-to-noise ratios >= 4; and the
      estimated metabolite concentrations had to display Cramer-Rao lower bounds of <=
      30%. MRS data (echo time/repetition time, 30/5000 ms; 3T) were acquired from the
      basal ganglia (BG), centrum semiovale (CS), and the cerebellum. The
      concentrations of five metabolites were measured: creatine, choline, N
      acetylaspartate, myo-inositol, and glutamate/glutamine complex (Glx). One hundred
      and eighty-four MR spectra were obtained (83 BG, 77 CS, and 24 cerebellum
      spectra). Creatine, N-acetylaspartate, and Glx displayed increases in their
      concentrations with PCA. Choline was not correlated with PCA in any region. As
      for myo-inositol, its concentration decreased with PCA in the BG, whereas it
      increased with PCA in the cerebellum. Quantitative brain metabolite
      concentrations and their changes during the neonatal period were assessed.
      Although the observed changes were partly similar to those detected in previous
      reports, our results are with more subjects (n = 83), and higher magnetic field
      (3T). The metabolite concentrations examined in this study and their changes are
      clinically useful indices of neonatal brain development. 

PMID- 24312434
TI  - Comparative metabolite fingerprinting of the rumen system during colonisation of
      three forage grass (Lolium perenne L.) varieties.
AB  - The rumen microbiota enable ruminants to degrade complex ligno-cellulosic
      compounds to produce high quality protein for human consumption. However, enteric
      fermentation by domestic ruminants generates negative by-products: greenhouse
      gases (methane) and environmental nitrogen pollution. The current lack of
      cultured isolates representative of the totality of rumen microbial species
      creates an information gap about the in vivo function of the rumen microbiota and
      limits our ability to apply predictive biology for improvement of feed for
      ruminants. In this work we took a whole ecosystem approach to understanding how
      the metabolism of the microbial population responds to introduction of its
      substrate. Fourier Transform Infra Red (FTIR) spectroscopy-based metabolite
      fingerprinting was used to discriminate differences in the plant-microbial
      interactome of the rumen when using three forage grass varieties (Lolium perenne
      L. cv AberDart, AberMagic and Premium) as substrates for microbial colonisation
      and fermentation. Specific examination of spectral regions associated with fatty
      acids, amides, sugars and alkanes indicated that although the three forages were
      apparently similar by traditional nutritional analysis, patterns of metabolite
      flux within the plant-microbial interactome were distinct and plant genotype
      dependent. Thus, the utilisation pattern of forage nutrients by the rumen
      microbiota can be influenced by subtleties determined by forage genotypes. These
      data suggest that our interactomic approach represents an important means to
      improve forages and ultimately the livestock environment. 

PMID- 24312435
TI  - Detection of synchronous cancers by fluorodeoxyglucose positron emission
      tomography/computed tomography during primary staging workup for esophageal
      squamous cell carcinoma in Taiwan.
AB  - AIM: The aim of this retrospective study was to investigate the ability of
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)
      in the detection of synchronous cancers during staging workup for esophageal
      squamous cell carcinoma. MATERIALS AND METHODS: We performed a retrospective
      chart review of 426 Taiwanese patients with esophageal cancer who received FDG
      PET/CT during their primary staging workup between December 2006 and December
      2011. We defined synchronous cancers as those occurring within 6 months of the
      FDG-PET/CT scan. All of the synchronous lesions were confirmed by histology or
      imaging follow-up. The study patients were followed for at least 18 months or
      were censored on the date of last follow-up. RESULTS: Fifty patients were
      excluded from analysis because of the presence of distant metastases. Of the
      remaining 376 patients, 359 were diagnosed with squamous cell carcinoma (SCC). We
      identified 17 patients with synchronous cancers, and all of them had a diagnosis
      of SCC. Synchronous head and neck cancers were the most frequent (n=13, 76.4%),
      followed by gastrointestinal cancers (colon cancer, n=2; hepatocellular
      carcinoma, n=1), and renal cell carcinoma (n=1). FDG-PET/CT successfully detected
      15 synchronous cancers (12 head and neck cancers, 2 colon cancers, and 1 renal
      cell carcinoma). In contrast, conventional workup detected only 9 synchronous
      cancers (7 head and neck cancers, 1 hepatocellular carcinoma and 1 renal cell
      carcinoma). The sensitivity of FDG-PET/CT and conventional workup in detecting
      synchronous cancers were 88.2% and 52.9% respectively. CONCLUSION: The most
      frequent synchronous lesions in patients with esophageal SCC were head and neck
      cancers in Taiwan. Our data indicate that FDG-PET/CT is superior to conventional
      workup in the detection of synchronous tumors during primary staging for
      esophageal squamous cell carcinoma.

PMID- 24312436
TI  - Egg-derived tri-peptide IRW exerts antihypertensive effects in spontaneously
      hypertensive rats.
AB  - BACKGROUND: There is a growing interest in using functional food components as
      therapy for cardiovascular diseases such as hypertension. We have previously
      characterized a tri-peptide IRW (Ile-Arg-Trp) from egg white protein
      ovotransferrin; this peptide showed anti-inflammatory, anti-oxidant and
      angiotensin converting enzyme (ACE) inhibitor properties in vitro. Given the
      pathogenic roles played by angiotensin, oxidative stress and inflammation in the
      spontaneously hypertensive rat (SHR), we tested the therapeutic potential of IRW
      in this well-established model of hypertension. METHODS AND RESULTS: 16-17 week
      old male SHRs were orally administered IRW at either a low dose (3 mg/Kg BW) or a
      high dose (15 mg/Kg BW) daily for 18 days. Blood pressure (BP) and heart rate
      were measured by telemetry. Animals were sacrificed at the end of the treatment
      for vascular function studies and measuring markers of inflammation. IRW
      treatment attenuated mean BP by ~10 mmHg and ~40 mmHg at the low- and high-dose
      groups respectively compared to untreated SHRs. Heart rate was not affected.
      Reduction in BP was accompanied by the restoration of diurnal variations in BP,
      preservation of nitric oxide dependent vasorelaxation, as well as reduction of
      plasma angiotensin II, other inflammatory markers and tissue fibrosis.
      CONCLUSION: Our results demonstrate anti-hypertensive effects of IRW in vivo
      likely mediated through ACE inhibition, endothelial nitric oxide synthase and
      anti-inflammatory properties.

PMID- 24312437
TI  - Turning cellulose waste into electricity: hydrogen conversion by a hydrogenase
      electrode.
AB  - Hydrogen-producing thermophilic cellulolytic microorganisms were isolated from
      cow faeces. Rates of cellulose hydrolysis and hydrogen formation were 0.2 mM L(
      1) h(-1) and 1 mM L(-1) h(-1), respectively. An enzymatic fuel cell (EFC) with a
      hydrogenase anode was used to oxidise hydrogen produced in a microbial
      bioreactor. The hydrogenase electrode was exposed for 38 days (912 h) to a
      thermophilic fermentation medium. The hydrogenase activity remaining after
      continuous operation under load was 73% of the initial value. 

PMID- 24312438
TI  - Understanding phenotypical character evolution in parmelioid lichenized fungi
      (Parmeliaceae, Ascomycota).
AB  - Parmelioid lichens form a species-rich group of predominantly foliose and
      fruticose lichenized fungi encompassing a broad range of morphological and
      chemical diversity. Using a multilocus approach, we reconstructed a phylogeny
      including 323 OTUs of parmelioid lichens and employed ancestral character
      reconstruction methods to understand the phenotypical evolution within this
      speciose group of lichen-forming fungi. Specifically, we were interested in the
      evolution of growth form, epicortex structure, and cortical chemistry. Since
      previous studies have shown that results may differ depending on the
      reconstruction method used, here we employed both maximum-parsimony and maximum
      likelihood approaches to reconstruct ancestral character states. We have also
      implemented binary and multistate coding of characters and performed parallel
      analyses with both coding types to assess for potential coding-based biases. We
      reconstructed the ancestral states for nine well-supported major clades in the
      parmelioid group, two higher-level sister groups and the ancestral character
      state for all parmelioid lichens. We found that different methods for coding
      phenotypical characters and different ancestral character state reconstruction
      methods mostly resulted in identical reconstructions but yield conflicting
      inferences of ancestral states, in some cases. However, we found support for the
      ancestor of parmelioid lichens having been a foliose lichen with a non-pored
      epicortex and pseudocyphellae. Our data suggest that some traits exhibit patterns
      of evolution consistent with adaptive radiation. 

PMID- 24312439
TI  - The MEK-ERK pathway is necessary for serine phosphorylation of mitochondrial
      STAT3 and Ras-mediated transformation.
AB  - Activating mutations in the RasGTPases are the most common oncogenic lesions in
      human cancer. Similarly, elevated STAT3 expression and/or phosphorylation are
      observed in the majority of human cancers. We recently found that activated Ras
      requires a mitochondrial rather than a nuclear activity of STAT3 to support
      cellular transformation. This mitochondrial activity of STAT3 was supported by
      phosphorylation on serine 727 (S727) in the carboxyl-terminus of STAT3. In this
      study we show that the H-Ras oncoprotein engages the MEK-ERK pathway to drive
      phosphorylation of STAT3 on S727, while phosphoinositide 3-kinase (PI3K) and mTOR
      activity were superfluous. Moreover, pharmacological inhibition of MEK reduced
      transformation by H-, K- or N-Ras. However, cells expressing a mitochondrially
      restricted STAT3 with a phospho-mimetic mutation at S727 were partially resistant
      to inhibition of the ERK pathway, exhibiting a partial rescue of anchorage
      independent cell growth in the presence of MEK inhibitor. This study shows that
      the MEK-ERK pathway is required for activated Ras-induced phosphorylation of
      STAT3 on S727, that inhibition of STAT3 S727 phosphorylation contributes to the
      anti-oncogenic potential of MEK inhibitors, and that mitochondrial STAT3 is one
      of the critical substrates of the Ras-MEK-ERK- axis during cellular
      transformation. 

PMID- 24312440
TI  - Elevated frequencies of circulating Th22 cell in addition to Th17 cell and
      Th17/Th1 cell in patients with acute coronary syndrome.
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory disease mediated by immune
      cells. Th22 cells are CD4(+) T cells that secret IL-22 but not IL-17 or IFN-gamma
      and are implicated in the pathogenesis of inflammatory disease. The roles of Th22
      cells in the pathophysiologic procedures of acute coronary syndrome (ACS) remain
      unclear. The purpose of this study is to investigate the profile of Th22, Th17
      and Th17/Th1 cells in ACS patients, including unstable angina (UA) and acute
      myocardial infarction (AMI) patients. DESIGN AND METHODS: In this study, 26 AMI
      patients, 16 UA patients, 16 stable angina (SA) patients and 16 healthy controls
      were included. The frequencies of Th22, Th17 and Th17/Th1 cells in AMI, UA, SA
      patients and healthy controls were examined by flow cytometry. Plasma levels of
      IL-22, IL-17 and IFN-gamma were measured by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Th22, Th17 and Th17/Th1 cells were significantly increased in
      AMI and UA patients compared with SA patients and healthy controls. Moreover,
      plasma IL-22 level was significantly elevated in AMI and UA patients. In
      addition, Th22 cells correlated positively with IL-22 as well as Th17 cells in
      AMI and UA patients. CONCLUSION: Our findings showed increased frequencies of
      both Th22 and Th17 cells in ACS patients, which suggest that Th22 and Th17 cells
      may play a potential role in plaque destabilization and the development of ACS.

PMID- 24312441
TI  - Treatment of anemia in inflammatory bowel disease--systematic review and meta
      analysis.
AB  - BACKGROUND: Anemia is considered the most common systemic complication of
      inflammatory bowel disease (IBD). We aimed to provide all available evidence
      regarding the safety and efficacy of therapy existing today to correct anemia in
      IBD. METHODS: Systematic review and meta-analysis of randomized controlled trials
      that compared any treatment for anemia in patients with IBD. We searched
      electronic databases, conference proceedings and clinical trials registries. Two
      reviewers independently extracted data from included trials. The primary outcome
      was the effect of treatment for anemia in IBD on the hemoglobin (Hb) response,
      defined as rate of patients who achieved an increase of 2 g/dl in Hb
      concentration at the end of the follow-up. Secondary outcomes included disease
      severity scores, iron indices, Hb levels, inflammatory markers, adverse effects,
      and mortality. Dichotomous data were analysed by calculating the relative risk
      (RR) for each trial with the uncertainty in each result being expressed using 95%
      confidence intervals (CI). A fixed effect model was used, except in the event of
      significant heterogeneity between the trials (P<0.10, I(2)>40%), in which we used
      a random effects model. RESULTS: Nine trials fulfilled the inclusion criteria, to
      a total of 973 patients. We were able to perform meta-analysis for intravenous
      (IV) versus oral iron and for ESAs versus placebo. IV iron was associated with a
      higher rate of achieving Hb response in comparison to oral iron; RR 1.25 (95% CI
      1.04-1.51, I(2) = 2%, 4 trials), CRP levels and disease activity indexes were not
      significantly affected by IV iron. IV iron was associated with a decrease in
      adverse events that required discontinuation of intervention and without an
      increase in serious adverse. DISCUSSION: Treatment for anemia in IBD should
      include IV iron and not oral iron replacement, due to improved Hb response, no
      added toxicity and no negative effect on disease activity.

PMID- 24312442
TI  - Megafaunal communities in rapidly warming fjords along the West Antarctic
      Peninsula: hotspots of abundance and beta diversity.
AB  - Glacio-marine fjords occur widely at high latitudes and have been extensively
      studied in the Arctic, where heavy meltwater inputs and sedimentation yield low
      benthic faunal abundance and biodiversity in inner-middle fjords. Fjord benthic
      ecosystems remain poorly studied in the subpolar Antarctic, including those in
      extensive fjords along the West Antarctic Peninsula (WAP). Here we test ecosystem
      predictions from Arctic fjords on three subpolar, glacio-marine fjords along the
      WAP. With seafloor photographic surveys we evaluate benthic megafaunal abundance,
      community structure, and species diversity, as well as the abundance of demersal
      nekton and macroalgal detritus, in soft-sediment basins of Andvord, Flandres and
      Barilari Bays at depths of 436-725 m. We then contrast these fjord sites with
      three open shelf stations of similar depths. Contrary to Arctic predictions, WAP
      fjord basins exhibited 3 to 38-fold greater benthic megafaunal abundance than the
      open shelf, and local species diversity and trophic complexity remained high from
      outer to inner fjord basins. Furthermore, WAP fjords contained distinct species
      composition, substantially contributing to beta and gamma diversity at 400-700 m
      depths along the WAP. The abundance of demersal nekton and macroalgal detritus
      was also substantially higher in WAP fjords compared to the open shelf. We
      conclude that WAP fjords are important hotspots of benthic abundance and
      biodiversity as a consequence of weak meltwater influences, low sedimentation
      disturbance, and high, varied food inputs. We postulate that WAP fjords differ
      markedly from their Arctic counterparts because they are in earlier stages of
      climate warming, and that rapid warming along the WAP will increase meltwater and
      sediment inputs, deleteriously impacting these biodiversity hotspots. Because WAP
      fjords also provide important habitat and foraging areas for Antarctic krill and
      baleen whales, there is an urgent need to develop better understanding of the
      structure, dynamics and climate-sensitivity of WAP subpolar fjord ecosystems. 

PMID- 24312443
TI  - Helicobacter pylori cholesteryl alpha-glucosides contribute to its pathogenicity
      and immune response by natural killer T cells.
AB  - Approximately 10-15% of individuals infected with Helicobacter pylori will
      develop ulcer disease (gastric or duodenal ulcer), while most people infected
      with H. pylori will be asymptomatic. The majority of infected individuals remain
      asymptomatic partly due to the inhibition of synthesis of cholesteryl alpha
      glucosides in H. pylori cell wall by alpha1,4-GlcNAc-capped mucin O-glycans,
      which are expressed in the deeper portion of gastric mucosa. However, it has not
      been determined how cholesteryl alpha-glucosyltransferase (alphaCgT), which forms
      cholesteryl alpha-glucosides, functions in the pathogenesis of H. pylori
      infection. Here, we show that the activity of alphaCgT from H. pylori clinical
      isolates is highly correlated with the degree of gastric atrophy. We investigated
      the role of cholesteryl alpha-glucosides in various aspects of the immune
      response. Phagocytosis and activation of dendritic cells were observed at similar
      degrees in the presence of wild-type H. pylori or variants harboring mutant forms
      of alphaCgT showing a range of enzymatic activity. However, cholesteryl alpha
      glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting
      an immune response in vitro and in vivo. Following inoculation of H. pylori
      harboring highly active alphaCgT into iNKT cell-deficient (Jalpha18(-/-)) or wild
      type mice, bacterial recovery significantly increased in Jalpha18(-/-) compared
      to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2
      cells dramatically decreased in Jalpha18(-/-) compared to wild-type mice. These
      findings demonstrate that cholesteryl alpha-glucosides play critical roles in H.
      pylori-mediated gastric inflammation and precancerous atrophic gastritis. 

PMID- 24312444
TI  - Macrophage specific caspase-1/11 deficiency protects against cholesterol
      crystallization and hepatic inflammation in hyperlipidemic mice.
AB  - BACKGROUND & AIMS: While non-alcoholic steatohepatitis (NASH) is characterized by
      hepatic steatosis combined with inflammation, the mechanisms triggering hepatic
      inflammation are unknown. In Ldlr(-/-) mice, we have previously shown that
      lysosomal cholesterol accumulation in Kupffer cells (KCs) correlates with hepatic
      inflammation and cholesterol crystallization. Previously, cholesterol crystals
      have been shown to induce the activation of inflammasomes. Inflammasomes are
      protein complexes that induce the processing and release of pro-inflammatory
      cytokines IL-1b and IL-18 via caspase-1 activation. Whereas caspase-1 activation
      is independent of caspase-11 in the canonical pathway of inflammasome activation,
      caspase-11 was found to trigger caspase-1-dependent IL-1b and IL-18 in response
      to non-canonical inflammasome activators. So far, it has not been investigated
      whether inflammasome activation stimulates the formation of cholesterol crystals.
      We hypothesized that inflammasome activation in KCs stimulates cholesterol
      crystallization, thereby leading to hepatic inflammation. METHODS: Ldlr (-/-)
      mice were transplanted (tp) with wild-type (Wt) or caspase-1/11(-/-) (dKO) bone
      marrow and fed either regular chow or a high-fat, high-cholesterol (HFC) diet for
      12 weeks. In vitro, bone marrow derived macrophages (BMDM) from wt or caspase
      1/11(-/-) mice were incubated with oxLDL for 24h and autophagy was assessed.
      RESULTS: In line with our hypothesis, caspase-1/11(-/-)-tp mice had less severe
      hepatic inflammation than Wt-tp animals, as evident from liver histology and gene
      expression analysis in isolated KCs. Mechanistically, KCs from caspase-1/11(-/-)
      tp mice showed less cholesterol crystals, enhanced cholesterol efflux and
      increased autophagy. In wt BMDM, oxLDL incubation led to disturbed autophagy
      activity whereas BMDM from caspase-1/11(-/-) mice had normal autophagy activity.
      CONCLUSION: Altogether, these data suggest a vicious cycle whereby disturbed
      autophagy and decreased cholesterol efflux leads to newly formed cholesterol
      crystals and thereby maintain hepatic inflammation during NASH by further
      activating the inflammasome.

PMID- 24312445
TI  - GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality
      in men.
AB  - The objective was to evaluate the hypothesis that growth-differentiation factor
      15 (GDF-15) is an independent marker of the long-term risk for both
      cardiovascular disease and cancer morbidity beyond clinical and biochemical risk
      factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala
      Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity
      data were obtained from public registries. At baseline there were independent
      associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of
      cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin
      C) and inflammatory activity (C-reactive protein), and previous cardiovascular
      disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115
      and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease
      mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561)
      cohort. After adjustment for conventional cardiovascular risk factors, one SD
      increase in log GDF-15 were, in the respective total and non-CVD populations,
      associated with 48% (95%CI 26 to 73%, p<0.001) and 67% (95%CI 28 to 217%,
      p<0.001) incremental risk of cardiovascular mortality, 48% (95%CI 33 to 67%,
      p<0.001) and 61% (95%CI 38 to 89%, p<0.001) of total mortality and 36% (95%CI 19
      to 56%, p<0.001) and 44% (95%CI 17 to 76%, p<0.001) of coronary heart disease
      morbidity and mortality. The corresponding incremental increase for cancer
      mortality in the respective total and non-cancer disease (n=882) population was
      46% (95%CI 21 to 77%, p<0.001) and 38% (95%CI 12 to 70%, p<0.001) and for cancer
      morbidity and mortality in patients without previous cancer disease 30% (95%CI 12
      to 51%, p<0.001). In conclusion, in elderly men, GDF-15 improves prognostication
      of both cardiovascular, cancer mortality and morbidity beyond established risk
      factors and biomarkers of cardiac, renal dysfunction and inflammation. 

PMID- 24312448
TI  - Neuropilar projections of the anterior gastric receptor neuron in the
      stomatogastric ganglion of the Jonah crab, Cancer borealis.
AB  - Sensory neurons provide important feedback to pattern-generating motor systems.
      In the crustacean stomatogastric nervous system (STNS), feedback from the
      anterior gastric receptor (AGR), a muscle receptor neuron, shapes the activity of
      motor circuits in the stomatogastric ganglion (STG) via polysynaptic pathways
      involving anterior ganglia. The AGR soma is located in the dorsal ventricular
      nerve posterior to the STG and it has been thought that its axon passes through
      the STG without making contacts. Using high-resolution confocal microscopy with
      dye-filled neurons, we show here that AGR from the crab Cancer borealis also has
      local projections within the STG and that these projections form candidate
      contact sites with STG motor neurons or with descending input fibers from other
      ganglia. We develop and exploit a new masking method that allows us to
      potentially separate presynaptic and postsynaptic staining of synaptic markers.
      The AGR processes in the STG show diversity in shape, number of branches and
      branching structure. The number of AGR projections in the STG ranges from one to
      three simple to multiply branched processes. The projections come in close
      contact with gastric motor neurons and descending neurons and may also be
      electrically coupled to other neurons of the STNS. Thus, in addition to well
      described long-loop pathways, it is possible that AGR is involved in integration
      and pattern regulation directly in the STG. 

PMID- 24312446
TI  - Efficacy and safety of dihydroartemisinin-piperaquine for treatment of Plasmodium
      vivax malaria in endemic countries: meta-analysis of randomized controlled
      studies.
AB  - BACKGROUND: This study aimed to synthesize available evidence on the efficacy of
      dihydroartemisinin-piperaquine (DHP) in treating uncomplicated Plasmodium vivax
      malaria in people living in endemic countries. METHODOLOGY AND PRINCIPAL
      FINDINGS: This is a meta-analysis of randomized controlled trials (RCT). We
      searched relevant studies in electronic databases up to May 2013. RCTs comparing
      efficacy of (DHP) with other artemisinin-based combination therapy (ACT), non-ACT
      or placebo were selected. The primary endpoint was efficacy expressed as PCR
      corrected parasitological failure. Efficacy was pooled by hazard ratio (HR) and
      95% CI, if studies reported time-to-event outcomes by the Kaplan-Meier method or
      data available for calculation of HR Nine RCTs with 14 datasets were included in
      the quantitative analysis. Overall, most of the studies were of high quality.
      Only a few studies compared with the same antimalarial drugs and reported the
      outcomes of the same follow-up duration, which created some difficulties in
      pooling of outcome data. We found the superiority of DHP over chloroquine (CQ)
      (at day > 42-63, HR:2.33, 95% CI:1.86-2.93, I (2): 0%) or artemether-lumefentrine
      (AL) (at day 42, HR:2.07, 95% CI:1.38-3.09, I (2): 39%). On the basis of GRADE
      criteria, further research is likely to have an important impact on our
      confidence in the estimate of effect and may change the estimate.
      DISCUSSION/CONCLUSION: Findings document that DHP is more efficacious than CQ and
      AL in treating uncomplicated P. vivax malaria. The better safety profile of DHP
      and the once-daily dosage improves adherence, and its fixed co-formulation
      ensures that both drugs (dihydroartemisinin and piperaquine) are taken together.
      However, DHP is not active against the hypnozoite stage of P. vivax. DHP has the
      potential to become an alternative antimalarial drug for the treatment
      uncomplicated P. vivax malaria. This should be substantiated by future RCTs with
      other ACTs. Additional work is required to establish how best to combine this
      treatment with appropriate antirelapse therapy (primaquine or other drugs under
      development).

PMID- 24312447
TI  - Atorvastatin treatment of rats with ischemia-reperfusion injury improves adipose
      derived mesenchymal stem cell migration and survival via the SDF-1alpha/CXCR-4
      axis.
AB  - BACKGROUND: Adipose-derived mesenchymal stem cells (ASCs) transplantation is a
      promising approach for myocardium repair. Promotion of ASCs migration and
      survival is the key for improving ASCs efficiency. SDF-1alpha is a critical
      factor responsible for ASCs migration and survival. Atorvastatin (Ator) is
      capable of up-regulating SDF-1alpha. Therefore, we're going to investigate
      whether ASCs migration and survival could be improved with atorvastatin. METHODS:
      In vitro study, cardiomyocytes were subjected to anoxia-reoxygenation injury and
      subsequently divided into different groups: group blank control, Ator, Ator plus
      L-NAME (A+L-NAME) and Ator plus AMD3100 (A+AMD3100).When migration analysis
      completed, cardiomyocytes were used for subsequent analyses. In vivo study, rats
      underwent ischemia-reperfusion injury were assigned into different groups
      corresponding to in vitro protocols. ASCs were transplanted on the seventh day of
      atorvastatin therapy. Seven days later, the rates of migration, differentiation
      and apoptosis were evaluated. RESULTS: Compared with other groups, ASCs migration
      in vitro was significantly improved in group Ator, which was dependent on SDF
      1alpha/CXCR-4 coupling. Results of in vivo study were consistent with that of in
      vitro study, further supporting the notion that the efficacy of atorvastatin on
      ASCs migration improvement was related to SDF-1alpha/CXCR-4 axis. Higher vessel
      density in group Ator might be another mechanism responsible for migration
      improvement. Concomitantly, apoptosis was significantly reduced in group Ator,
      whereas no significant difference of differentiation was found. CONCLUSION:
      Migration and survival of ASCs could be improved by atorvastatin under ischemia
      reperfusion injury, which were ascribed to SDF-1alpha/CXCR-4 axis.

PMID- 24312449
TI  - In silico studies in probing the role of kinetic and structural effects of
      different drugs for the reactivation of tabun-inhibited AChE.
AB  - We have examined the reactivation mechanism of the tabun-conjugated AChE with
      various drugs using density functional theory (DFT) and post-Hartree-Fock
      methods. The electronic environments and structural features of neutral oximes
      (deazapralidoxime and 3-hydroxy-2-pyridinealdoxime) and charged monopyridinium
      oxime (2-PAM) and bispyridinium oxime (Ortho-7) are different, hence their
      efficacy varies towards the reactivation process of tabun-conjugated AChE. The
      calculated potential energy surfaces suggest that a monopyridinium reactivator is
      less favorable for the reactivation of tabun-inhibited AChE compared to a bis
      quaternary reactivator, which substantiates the experimental study. The rate
      determining barrier with neutral oximes was found to be ~2.5 kcal/mol, which was
      ~5.0 kcal/mol lower than charged oxime drugs such as Ortho-7. The structural
      analysis of the calculated geometries suggest that the charged oximes form strong
      O(...)H and N(...)H hydrogen bonding and C-H(...)pi non-bonding interaction with
      the tabun-inhibited enzyme to stabilize the reactant complex compared to
      separated reactants, which influences the activation barrier. The ability of
      neutral drugs to cross the blood-brain barrier was also found to be superior to
      charged antidotes, which corroborates the available experimental observations.
      The calculated activation barriers support the superiority of neutral oximes for
      the activation of tabun-inhibited AChE compared to charged oximes. However, they
      lack effective interactions with their peripheral sites. Docking studies revealed
      that the poor binding affinity of simple neutral oxime drugs such as 3-hydroxy-2
      pyridinealdoxime inside the active-site gorge of AChE was significantly augmented
      with the addition of neutral peripheral units compared to conventional charged
      peripheral sites. The newly designed oxime drug 2 appears to be an attractive
      candidate as efficient antidote to kinetically and structurally reactivate the
      tabun-inhibited enzyme. 

PMID- 24312450
TI  - Prospective validation of immunological infiltrate for prediction of response to
      neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the
      neoadjuvant GeparQuinto trial.
AB  - INTRODUCTION: We have recently described an increased lymphocytic infiltration
      rate in breast carcinoma tissue is a significant response predictor for
      anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study
      was to prospectively validate the tumor-associated lymphocyte infiltrate as
      predictive marker for response to anthracycline/taxane-based NACT. PATIENTS AND
      METHODS: The immunological infiltrate was prospectively evaluated in a total of
      313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a
      substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy),
      stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer
      (LPBC) were evaluated by histopathological assessment. Pathological complete
      response (pCR) rates were analyzed and compared between the defined subgroups
      using the exact test of Fisher. RESULTS: Patients with lymphocyte-predominant
      breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to
      non-LPBC patients (14.3%, p<0.001). LPBC and stromal lymphocytes were
      significantly independent predictors for pCR in multivariate analysis (LPBC: OR
      2.7, p = 0.003, strLy: OR 1.2, p = 0.01). The amount of intratumoral lymphocytes
      was significantly predictive for pCR in univariate (OR 1.2, p = 0.01) but not in
      multivariate logistic regression analysis (OR 1.2, p = 0.11). CONCLUSION:
      Confirming previous investigations of our group, we have prospectively validated
      in an independent cohort that an increased immunological infiltrate in breast
      tumor tissue is predictive for response to anthracycline/taxane-based NACT.
      Patients with LPBC and increased stromal lymphocyte infiltration have
      significantly increased pCR rates. The lymphocytic infiltrate is a promising
      additional parameter for histopathological evaluation of breast cancer core
      biopsies.

PMID- 24312451
TI  - Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro,
      in silico, and clinical studies.
AB  - The translation of in vitro findings to clinical outcomes is often elusive.
      Trauma/hemorrhagic shock (T/HS) results in hepatic hypoxia that drives
      inflammation. We hypothesize that in silico methods would help bridge in vitro
      hepatocyte data and clinical T/HS, in which the liver is a primary site of
      inflammation. Primary mouse hepatocytes were cultured under hypoxia (1% O2) or
      normoxia (21% O2) for 1-72 h, and both the cell supernatants and protein lysates
      were assayed for 18 inflammatory mediators by LuminexTM technology. Statistical
      analysis and data-driven modeling were employed to characterize the main
      components of the cellular response. Statistical analyses, hierarchical and k
      means clustering, Principal Component Analysis, and Dynamic Network Analysis
      suggested MCP-1/CCL2 and IL-1alpha as central coordinators of hepatocyte-mediated
      inflammation in C57BL/6 mouse hepatocytes. Hepatocytes from MCP-1-null mice had
      altered dynamic inflammatory networks. Circulating MCP-1 levels segregated human
      T/HS survivors from non-survivors. Furthermore, T/HS survivors with elevated
      early levels of plasma MCP-1 post-injury had longer total lengths of stay, longer
      intensive care unit lengths of stay, and prolonged requirement for mechanical
      ventilation vs. those with low plasma MCP-1. This study identifies MCP-1 as a
      main driver of the response of hepatocytes in vitro and as a biomarker for
      clinical outcomes in T/HS, and suggests an experimental and computational
      framework for discovery of novel clinical biomarkers in inflammatory diseases. 

PMID- 24312452
TI  - Genome-wide comparison of cowpox viruses reveals a new clade related to Variola
      virus.
AB  - Zoonotic infections caused by several orthopoxviruses (OPV) like monkeypox virus
      or vaccinia virus have a significant impact on human health. In Europe, the
      number of diagnosed infections with cowpox viruses (CPXV) is increasing in
      animals as well as in humans. CPXV used to be enzootic in cattle; however, such
      infections were not being diagnosed over the last decades. Instead, individual
      cases of cowpox are being found in cats or exotic zoo animals that transmit the
      infection to humans. Both animals and humans reveal local exanthema on arms and
      legs or on the face. Although cowpox is generally regarded as a self-limiting
      disease, immunosuppressed patients can develop a lethal systemic disease
      resembling smallpox. To date, only limited information on the complex and,
      compared to other OPV, sparsely conserved CPXV genomes is available. Since CPXV
      displays the widest host range of all OPV known, it seems important to comprehend
      the genetic repertoire of CPXV which in turn may help elucidate specific
      mechanisms of CPXV pathogenesis and origin. Therefore, 22 genomes of independent
      CPXV strains from clinical cases, involving ten humans, four rats, two cats, two
      jaguarundis, one beaver, one elephant, one marah and one mongoose, were sequenced
      by using massive parallel pyrosequencing. The extensive phylogenetic analysis
      showed that the CPXV strains sequenced clearly cluster into several distinct
      clades, some of which are closely related to Vaccinia viruses while others
      represent different clades in a CPXV cluster. Particularly one CPXV clade is more
      closely related to Camelpox virus, Taterapox virus and Variola virus than to any
      other known OPV. These results support and extend recent data from other groups
      who postulate that CPXV does not form a monophyletic clade and should be divided
      into multiple lineages. 

PMID- 24312453
TI  - Adaptation of CD8 T cell responses to changing HIV-1 sequences in a cohort of HIV
      1 infected individuals not selected for a certain HLA allele.
AB  - HIV evades CD8 T cell mediated pressure by viral escape mutations in targeted CD8
      T cell epitopes. A viral escape mutation can lead to a decline of the respective
      CD8 T cell response. Our question was what happened after the decline of a CD8 T
      cell response and - in the case of viral escape - if a new CD8 T cell response
      towards the mutated antigen could be generated in a population not selected for
      certain HLA alleles. We studied 19 antiretroviral-naive HIV-1 infected
      individuals with different disease courses longitudinally. A median number of 12
      (range 2-24) CD8 T cell responses towards Gag and Nef were detected per study
      subject. A total of 30 declining CD8 T cell responses were studied in detail and
      viral sequence analyses showed amino acid changes in 25 (83%) of these. Peptide
      titration assays and definition of optimal CD8 T cell epitopes revealed 12 viral
      escape mutations with one de-novo response (8%). The de-novo response, however,
      showed less effector functions than the original CD8 T cell response. In addition
      we identified 4 shifts in immunodominance. For one further shift in
      immunodominance, the mutations occurred outside the optimal epitope and might
      represent processing changes. Interestingly, four adaptations to the virus (the
      de-novo response and 3 shifts in immunodominance) occurred in the group of
      chronically infected progressors. None of the subjects with adaptation to the
      changing virus carried the HLA alleles B57, B*58:01 or B27. Our results show that
      CD8 T cell responses adapt to the mutations of HIV. However it was limited to
      only 20% (5 out of 25) of the epitopes with viral sequence changes in a cohort
      not expressing protective HLA alleles. 

PMID- 24312454
TI  - Characterization and drug resistance patterns of Ewing's sarcoma family tumor
      cell lines.
AB  - Despite intensive treatment with chemotherapy, radiotherapy and surgery, over 70%
      of patients with metastatic Ewing's Sarcoma Family of Tumors (EFT) will die of
      their disease. We hypothesize that properly characterized laboratory models
      reflecting the drug resistance of clinical tumors will facilitate the application
      of new therapeutic agents to EFT. To determine resistance patterns, we studied
      newly established EFT cell lines derived from different points in therapy: two
      established at diagnosis (CHLA-9, CHLA-32), two after chemotherapy and
      progressive disease (CHLA-10, CHLA-25), and two at relapse after myeloablative
      therapy and autologous bone marrow transplantation (post-ABMT) (CHLA-258, COG-E
      352). The new lines were compared to widely studied EFT lines TC-71, TC-32, SK-N
      MC, and A-673. These lines were extensively characterized with regard to identity
      (short tandem repeat (STR) analysis), p53, p16/14 status, and EWS/ETS breakpoint
      and target gene expression profile. The DIMSCAN cytotoxicity assay was used to
      assess in vitro drug sensitivity to standard chemotherapy agents. No association
      was found between drug resistance and the expression of EWS/ETS regulated genes
      in the EFT cell lines. No consistent association was observed between drug
      sensitivity and p53 functionality or between drug sensitivity and p16/14
      functionality across the cell lines. Exposure to chemotherapy prior to cell line
      initiation correlated with drug resistance of EFT cell lines in 5/8 tested agents
      at clinically achievable concentrations (CAC) or the lower tested concentration
      (LTC): (cyclophosphamide (as 4-HC) and doxorubicin at CAC, etoposide, irinotecan
      (as SN-38) and melphalan at LTC; P<0.1 for one agent, and P<0.05 for four agents.
      This panel of well-characterized drug-sensitive and drug-resistant cell lines
      will facilitate in vitro preclinical testing of new agents for EFT. 

PMID- 24312455
TI  - Metapopulation dynamics enable persistence of influenza A, including A/H5N1, in
      poultry.
AB  - Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human
      illness and death since 1997. Yet it is still unclear how this pathogen is able
      to persist globally. While wild birds seem to be a genetic reservoir for
      influenza A, they do not seem to be the main source of human illness. Here, we
      highlight the role that domestic poultry may play in maintaining A/H5N1 globally,
      using theoretical models of spatial population structure in poultry populations.
      We find that a metapopulation of moderately sized poultry flocks can sustain the
      pathogen in a finite poultry population for over two years. Our results suggest
      that it is possible that moderately intensive backyard farms could sustain the
      pathogen indefinitely in real systems. This fits a pattern that has been observed
      from many empirical systems. Rather than just employing standard culling
      procedures to control the disease, our model suggests ways that poultry
      production systems may be modified. 

PMID- 24312456
TI  - Adverse selection? A multi-dimensional profile of people dispensed opioid
      analgesics for persistent non-cancer pain.
AB  - OBJECTIVES: This study investigates utilisation patterns for prescription opioid
      analgesics in the Australian community and how these are associated with a
      framework of individual-level factors related to healthcare use. METHODS: Self
      reported demographic and health information from participants in the 45 and Up
      Study cohort were linked to pharmaceutical claims from 2006-2009. Participants
      comprised 19,816 people with >=1 opioid analgesic dispensing in the 12-months
      after recruitment to the cohort and 79,882 people not dispensed opioid
      analgesics. All participants were aged >=45 years, were social security
      pharmaceutical beneficiaries, with no history of cancer. People dispensed opioid
      analgesics were classified as having acute (dispensing period <90 days), episodic
      (>=90 days and <3 'authority' prescriptions for increased quantity supply) or
      long-term treatment (>=90 days and >=3 authority prescriptions). RESULTS: Of
      participants dispensed opioid analgesic 52% received acute treatment, 25%
      episodic treatment and 23% long-term treatment. People dispensed opioid
      analgesics long-term had an average of 14.9 opioid analgesic prescriptions/year
      from 2.0 doctors compared with 1.5 prescriptions from 1.1 doctors for people
      receiving acute treatment. People dispensed opioid analgesics reported more need
      related factors such as poorer physical functioning and higher psychological
      distress. Long-term users were more likely to have access-related factors such as
      low-income and living outside major cities. After simultaneous adjustment,
      association with predisposing health factors and access diminished, but
      indicators of need such as osteoarthritis treatment, paracetamol use, and poor
      physical function were the strongest predictors for all opioid analgesic users.
      CONCLUSIONS: People dispensed opioid analgesics were in poorer health, reported
      higher levels of distress and poorer functioning than people not receiving opioid
      analgesics. Varying dispensing profiles were evident among people dispensed
      opioid analgesics for persistent pain, with those receiving episodic and long
      term treatment dispensed the strongest opioid analgesics. The findings highlight
      the broad range of factors associated with longer term opioid analgesics use.

PMID- 24312457
TI  - Homotypic and heterotypic adhesion induced by odorant receptors and the beta2
      adrenergic receptor.
AB  - In the mouse olfactory system regulated expression of a large family of G Protein
      Coupled Receptors (GPCRs), the Odorant Receptors (ORs), provides each sensory
      neuron with a single OR identity. In the wiring of the olfactory sensory neuron
      projections, a complex axon sorting process ensures the segregation of >1,000
      subpopulations of axons of the same OR identity into homogeneously innervated
      glomeruli. ORs are critical determinants in axon sorting, and their presence on
      olfactory axons raises the intriguing possibility that they may participate in
      axonal wiring through direct or indirect trans-interactions mediating adhesion or
      repulsion between axons. In the present work, we used a biophysical assay to test
      the capacity of ORs to induce adhesion of cell doublets overexpressing these
      receptors. We also tested the beta2 Adrenergic Receptor, a non-OR GPCR known to
      recapitulate the functions of ORs in olfactory axon sorting. We report here the
      first evidence for homo- and heterotypic adhesion between cells overexpressing
      the ORs MOR256-17 or M71, supporting the hypothesis that ORs may contribute to
      olfactory axon sorting by mediating differential adhesion between axons. 

PMID- 24312459
TI  - Types of social capital and mental disorder in deprived urban areas: a multilevel
      study of 40 disadvantaged London neighbourhoods.
AB  - OBJECTIVES: To examine the extent to which individual and ecological-level
      cognitive and structural social capital are associated with common mental
      disorder (CMD), the role played by physical characteristics of the neighbourhood
      in moderating this association, and the longitudinal change of the association
      between ecological level cognitive and structural social capital and CMD. DESIGN:
      Cross-sectional and longitudinal study of 40 disadvantaged London neighbourhoods.
      We used a contextual measure of the physical characteristics of each
      neighbourhood to examine how the neighbourhood moderates the association between
      types of social capital and mental disorder. We analysed the association between
      ecological-level measures of social capital and CMD longitudinally. PARTICIPANTS:
      4,214 adults aged 16-97 (44.4% men) were randomly selected from 40 disadvantaged
      London neighbourhoods. MAIN OUTCOME MEASURES: General Health Questionnaire (GHQ
      12). RESULTS: Structural rather than cognitive social capital was significantly
      associated with CMD after controlling for socio-demographic variables. However,
      the two measures of structural social capital used, social networks and civic
      participation, were negatively and positively associated with CMD respectively.
      'Social networks' was negatively associated with CMD at both the individual and
      ecological levels. This result was maintained when contextual aspects of the
      physical environment (neighbourhood incivilities) were introduced into the model,
      suggesting that 'social networks' was independent from characteristics of the
      physical environment. When ecological-level longitudinal analysis was conducted,
      'social networks' was not statistically significant after controlling for
      individual-level social capital at follow up. CONCLUSIONS: If we conceptually
      distinguish between cognitive and structural components as the quality and
      quantity of social capital respectively, the conclusion of this study is that the
      quantity rather than quality of social capital is important in relation to CMD at
      both the individual and ecological levels in disadvantaged urban areas. Thus,
      policy should support interventions that create and sustain social networks. One
      of these is explored in this article. TRIAL REGISTRATION: Controlled-Trials.com
      ISRCTN68175121 http://www.controlled-trials.com/ISRCTN68175121.

PMID- 24312458
TI  - Metabolomic profile of umbilical cord blood plasma from early and late
      intrauterine growth restricted (IUGR) neonates with and without signs of brain
      vasodilation.
AB  - OBJECTIVES: To characterize via NMR spectroscopy the full spectrum of metabolic
      changes in umbilical vein blood plasma of newborns diagnosed with different
      clinical forms of intrauterine growth restriction (IUGR). METHODS: 23 early IUGR
      cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR
      cases with 56 matched AGAs were included in this study. Early IUGR was defined as
      a birth weight <10(th) centile, abnormal umbilical artery (UA) Doppler and
      delivery <35 weeks. Late IUGR was defined as a birth weight <10(th) centile with
      normal UA Doppler and delivery >35 weeks. This group was subdivided in 18
      vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth
      weight >10(th) centile. (1)H nuclear magnetic resonance (NMR) metabolomics of the
      blood samples collected from the umbilical vein at delivery was obtained.
      Multivariate statistical analysis identified several metabolites that allowed the
      discrimination between the different IUGR subgroups, and their comparative levels
      were quantified from the NMR data. RESULTS: The NMR-based analysis showed
      increased unsaturated lipids and VLDL levels in both early and late IUGR samples,
      decreased glucose and increased acetone levels in early IUGR. Non-significant
      trends for decreased glucose and increased acetone levels were present in late
      IUGR, which followed a severity gradient when the VD and non-VD subgroups were
      considered. Regarding amino acids and derivatives, early IUGR showed
      significantly increased glutamine and creatine levels, whereas the amounts of
      phenylalanine and tyrosine were decreased in early and late-VD IUGR samples.
      Valine and leucine were decreased in late IUGR samples. Choline levels were
      decreased in all clinical subforms of IUGR. CONCLUSIONS: IUGR is not associated
      with a unique metabolic profile, but important changes are present in different
      clinical subsets used in research and clinical practice. These results may help
      in characterizing comprehensively specific alterations underlying different IUGR
      subsets.

PMID- 24312460
TI  - Eco-genetic structure of Bacillus cereus sensu lato populations from different
      environments in northeastern Poland.
AB  - The Bacillus cereus group, which includes entomopathogens and etiologic agents of
      foodborne illness or anthrax, persists in various environments. The basis of
      their ecological diversification remains largely undescribed. Here we present the
      genetic structure and phylogeny of 273 soil B. cereus s.l. isolates from diverse
      habitats in northeastern Poland, with samplings acquired from the last European
      natural forest (Bialowieza National Park), the largest marshes in Europe (Biebrza
      National Park), and a farm. In multi-locus sequence typing (MLST), despite
      negative selection in seven housekeeping loci, the isolates exhibited high
      genetic diversity (325 alleles), mostly resulting from mutation events, and
      represented 148 sequencing types (131 STs new and 17 STs already described)
      grouped into 19 complexes corresponding with bacterial clones, and 80 singletons.
      Phylogenetic analyses showed that 74% of the isolates clustered with B. cereus
      s.l. environmental references (clade III), while only 11 and 15%, respectively,
      grouped with isolates of clinical origin (clade I), and B. cereus ATCC 14579 and
      reference B. thuringiensis (clade II). Predominantly within clade III, we found
      lineages adapted to low temperature (thermal ecotypes), while putative toxigenic
      isolates (cytK-positive) were scattered in all clades of the marsh and farm
      samplings. The occurrence of 92% of STs in bacilli originating from one habitat,
      and the description of new STs for 78% of the isolates, strongly indicate the
      existence of specific genotypes within the natural B. cereus s.l. populations. In
      contrast to the human-associated B. cereus s.l. that exhibit a significant level
      of similarity, the environmental isolates appear more complex. Thus we propose
      dividing B. cereus s.l. into two groups, the first including environmental
      isolates, and the second covering those that are of clinical relevance. 

PMID- 24312461
TI  - The prevalence and characteristics of metabolic syndrome in patients with
      vertigo.
AB  - OBJECTIVES/HYPOTHESIS: Metabolic syndrome (MetS) is a condition that increases
      the risk of coronary artery disease and cerebral infarction. We determined the
      prevalence of MetS in vertigo patients and clinically investigated the
      association between MetS and vertigo. STUDY DESIGN: Case-control study. METHODS:
      The subjects were 333 patients, including 107 males and 226 females, who
      presented with vertigo as a primary symptom. MetS was diagnosed according to the
      International Diabetes Federation definition, which is based on waist
      circumference, blood serum levels, and blood pressure. RESULTS: MetS was detected
      in 53 (15.9%) of 333 vertigo patients, including 24 males (22.4%) and 29 females
      (12.8%); i.e., the frequency of MetS was significantly higher among the male
      patients than the female patients. The overall prevalence of MetS (15.9%) among
      vertigo patients did not differ from that observed among general adults in
      previous Japanese surveillance studies; however, MetS was significantly more
      common among the vertigo patients in males than general adult males. The
      prevalence of MetS was also examined in five types of vertigo, Concomitant MetS
      was noted in many males with vertebrobasilar insufficiency (VBI) and isolated
      vertigo of unknown etiology. CONCLUSION: It was suggested that MetS is involved
      in the development of vertigo in males. MetS might be a risk factor for vascular
      vertigo such as VBI in males. The high frequency of MetS among males with vertigo
      of unknown etiology suggested that the pathogenesis of metabolic syndrome is
      involved in this type of isolated vertigo.

PMID- 24312462
TI  - Immunolocalization of an amino-terminal fragment of apolipoprotein E in the
      Pick's disease brain.
AB  - Although the risk factor for apolipoprotein E (apoE) polymorphism in Alzheimer's
      disease (AD) has been well described, the role that apoE plays in other
      neurodegenerative diseases, including Pick's disease, is not well established. To
      examine a possible role of apoE in Pick's disease, an immunohistochemical
      analysis was performed utilizing a novel site-directed antibody that is specific
      for an amino-terminal fragment of apoE. Application of this antibody, termed the
      amino-terminal apoE cleavage fragment (nApoECF) antibody, consistently labeled
      Pick bodies within area CA1 of the hippocampus in 4 of the 5 cases examined. Co
      localization of the nApoECF antibody with PHF-1, a general marker for Pick
      bodies, as well as with an antibody to caspase-cleaved tau (TauC3) was evident
      within the hippocampus. While staining of the nApoECF antibody was robust in area
      CA1, little co-localization with PHF-1 in Pick bodies within the dentate gyrus
      was observed. A quantitative analysis indicated that approximately 86% of the
      Pick bodies identified in area CA1 labeled with the nApoECF antibody. The
      presence of truncated apoE within Pick bodies suggests a broader role of apoE
      beyond AD and raises the question as to whether this protein contributes to
      pathogenesis associated with Pick's disease. 

PMID- 24312463
TI  - DNase gamma is the effector endonuclease for internucleosomal DNA fragmentation
      in necrosis.
AB  - Apoptosis and necrosis, two major forms of cell death, can be distinguished
      morphologically and biochemically. Internucleosomal DNA fragmentation (INDF) is a
      biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known
      as DNA fragmentation factor 40 kDa (DFF40), is one of the major effector
      endonucleases. DNase gamma, a Mg(2+)/Ca(2+)-dependent endonuclease, is also known
      to generate INDF but its role among other apoptosis-associated endonucleases in
      cell death is unclear. Here we show that (i) INDF occurs even during necrosis in
      cell lines, primary cells, and in tissues of mice in vivo, and (ii) DNase gamma,
      but not CAD, is the effector endonuclease for INDF in cells undergoing necrosis.
      These results document a previously unappreciated role for INDF in necrosis and
      define its molecular basis. 

PMID- 24312464
TI  - Analysis of the stress and displacement distribution of inferior tibiofibular
      syndesmosis injuries repaired with screw fixation: a finite element study.
AB  - BACKGROUND: Studies of syndesmosis injuries have concentrated on cadaver models.
      However, they are unable to obtain exact data regarding the stress and
      displacement distribution of various tissues, and it is difficult to compare
      models. We investigated the biomechanical effects of inferior tibiofibular
      syndesmosis injuries (ITSIs) and screw fixation on the ankle using the finite
      element (FE) method. METHODOLOGY/PRINCIPAL FINDINGS: A three-dimensional model of
      a healthy ankle complex was developed using computed tomography (CT) images. We
      established models of an ITSI and of screw fixation at the plane 2.5 cm above and
      parallel to the tibiotalar joint surface of the injured syndesmosis. Simulated
      loads were applied under three conditions: neutral position with single-foot
      standing and internal and external rotation of the ankle. ITSI reduced contact
      forces between the talus and fibula, helped periarticular ankle ligaments
      withstand more load-resisting movement, and increased the magnitude of
      displacement at the lower extreme of the tibia and fibula. ITSI fixation with a
      syndesmotic screw reduced contact forces in all joints, decreased the magnitude
      of displacement at the lower extreme of the tibia and fibula, and increased
      crural interosseous membrane stress. CONCLUSIONS/SIGNIFICANCE: Severe syndesmosis
      injuries cause stress and displacement distribution of the ankle to change
      multidirectional ankle instability and should be treated by internal fixation.
      Though the transverse syndesmotic screw effectively stabilizes syndesmotic
      diastasis, it also changes stress distribution around the ankle and decreases the
      joint's range of motion (ROM). Therefore, fixation should not be performed for a
      long period of time because it is not physiologically suitable for the ankle
      joint.

PMID- 24312465
TI  - Low body weight in females is a risk factor for increased tenofovir exposure and
      drug-related adverse events.
AB  - Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone
      diseases. Factors associated with these drug-related adverse events are poorly
      characterized. Our objective was to investigate such factors in patients treated
      long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with
      basal creatinine clearance >80 mL/min treated with tenofovir for at least 6
      months and with at least one assessment of tenofovir plasma trough concentrations
      were considered. Tenofovir-associated adverse events were defined as the
      appearance of pathological proteinuria, worsening of renal function or bone
      demineralization. By multivariate regression analysis, we found that serum
      creatinine (p = 0.003) and body weight (p = 0.002) were the factors independently
      associated with plasma tenofovir concentrations. In particular, women with body
      weight<50 kg had significantly higher plasma tenofovir concentrations than those
      weighting >50 Kg (160+/-93 vs.71+/-52 ng/mL, p<0.001). High tenofovir plasma
      trough concentrations and the age of the patients were independently associated
      with the development of drug-related kidney and bone toxicity. In this
      retrospective study we have shown that HIV-infected women with low body weight
      are at risk to be exposed to high tenofovir plasma trough concentrations,
      ultimately resulting in a significant hazard to develop long-term tenofovir
      complications. 

PMID- 24312466
TI  - The strengths and difficulties questionnaire as a predictor of parent-reported
      diagnosis of autism spectrum disorder and attention deficit hyperactivity
      disorder.
AB  - The Strengths and Difficulties Questionnaire (SDQ) is widely used as an
      international standardised instrument measuring child behaviour. The primary aim
      of our study was to examine whether behavioral symptoms measured by SDQ were
      elevated among children with autism spectrum disorder (ASD) and attention deficit
      hyperactivity disorder (ADHD) relative to the rest of the population, and to
      examine the predictive value of the SDQ for outcome of parent-reported clinical
      diagnosis of ASD/ADHD. A secondary aim was to examine the extent of overlap in
      symptoms between children diagnosed with these two disorders, as measured by the
      SDQ subscales. A cross-sectional secondary analysis of data from the Millennium
      Birth Cohort (n = 19,519), was conducted. Data were weighted to be representative
      of the UK population as a whole. ADHD or ASD identified by a medical doctor or
      health professional were reported by parents in 2008 and this was the case
      definition of diagnosis; (ADHD n = 173, ASD n = 209, excluding twins and
      triplets). Study children's ages ranged from 6.3-8.2 years; (mean 7.2 years).
      Logistic regression was used to examine the association between the parent
      reported clinical diagnosis of ASD/ADHD and teacher and parent-reported SDQ
      subscales. All SDQ subscales were strongly associated with both ASD and ADHD.
      There was substantial co-occurrence of behavioral difficulties between children
      diagnosed with ASD and those diagnosed with ADHD. After adjustment for other
      subscales, the final model for ADHD, contained hyperactivity/inattention and
      impact symptoms only and had a sensitivity of 91% and specificity of 90%; (AUC) =
      0.94 (95% CI, 0.90-0.97). The final model for ASD was composed of all subscales
      except the 'peer problems' scales, indicating of the complexity of behavioural
      difficulties that may accompany ASD. A threshold of 0.03 produced model
      sensitivity and specificity of 79% and 93% respectively; AUC = 0.90 (95% CI, 0.86
      0.95). The results support changes to DSM-5 removing exclusivity clauses. 

PMID- 24312467
TI  - Electrophysiological correlation of the degree of self-reference effect.
AB  - The present study investigated neural correlations underlying the psychological
      processing of stimuli with various degrees of self-relevance. Event-related
      potentials were recorded for names that differ in their extent of relevance to
      the study participant. Participants performed a three-stimulus oddball task. ERP
      results showed larger P2 averaged amplitudes for highly self-relevant names than
      for moderately self-relevant, minimally self-relevant, and non-self-relevant
      names. N2 averaged amplitudes were larger for the highly self-relevant names than
      for the moderately self-relevant, minimally self-relevant, and non-self-relevant
      names. Highly self-relevant names elicited larger P3 averaged amplitudes than the
      moderately self-relevant names which, in turn, had larger P3 values than for
      minimally self-relevant names. Minimally self-relevant stimuli elicited larger P3
      averaged amplitudes than non-self-relevant stimuli. These results demonstrate a
      degree effect of self-reference, which was indexed using electrophysiological
      activity. 

PMID- 24312468
TI  - Linkage study and exome sequencing identify a BDP1 mutation associated with
      hereditary hearing loss.
AB  - Nonsyndromic Hereditary Hearing Loss is a common disorder accounting for at least
      60% of prelingual deafness. GJB2 gene mutations, GJB6 deletion, and the A1555G
      mitochondrial mutation play a major role worldwide in causing deafness, but there
      is a high degree of genetic heterogeneity and many genes involved in deafness
      have not yet been identified. Therefore, there remains a need to search for new
      causative mutations. In this study, a combined strategy using both linkage
      analysis and sequencing identified a new mutation causing hearing loss. Linkage
      analysis identified a region of 40 Mb on chromosome 5q13 (LOD score 3.8) for
      which exome sequencing data revealed a mutation (c.7873 T>G leading to
      p.*2625Gluext*11) in the BDP1 gene (B double prime 1, subunit of RNA polymerase
      III transcription initiation factor IIIB) in patients from a consanguineous
      Qatari family of second degree, showing bilateral, post-lingual, sensorineural
      moderate to severe hearing impairment. The mutation disrupts the termination
      codon of the transcript resulting in an elongation of 11 residues of the BDP1
      protein. This elongation does not contain any known motif and is not conserved
      across species. Immunohistochemistry studies carried out in the mouse inner ear
      showed Bdp1 expression within the endothelial cells in the stria vascularis, as
      well as in mesenchyme-derived cells surrounding the cochlear duct. The
      identification of the BDP1 mutation increases our knowledge of the molecular
      bases of Nonsyndromic Hereditary Hearing Loss and provides new opportunities for
      the diagnosis and treatment of this disease in the Qatari population. 

PMID- 24312469
TI  - Production and robustness of a Cacao agroecosystem: effects of two contrasting
      types of management strategies.
AB  - Ecological intensification, i.e. relying on ecological processes to replace
      chemical inputs, is often presented as the ideal alternative to conventional
      farming based on an intensive use of chemicals. It is said to both maintain high
      yield and provide more robustness to the agroecosystem. However few studies
      compared the two types of management with respect to their consequences for
      production and robustness toward perturbation. In this study our aim is to assess
      productive performance and robustness toward diverse perturbations of a Cacao
      agroecosystem managed with two contrasting groups of strategies: one group of
      strategies relying on a high level of pesticides and a second relying on low
      levels of pesticides. We conducted this study using a dynamical model of a Cacao
      agroecosystem that includes Cacao production dynamics, and dynamics of three
      insects: a pest (the Cacao Pod Borer, Conopomorpha cramerella) and two
      characteristic but unspecified beneficial insects (a pollinator of Cacao and a
      parasitoid of the Cacao Pod Borer). Our results showed two opposite behaviors of
      the Cacao agroecosystem depending on its management, i.e. an agroecosystem
      relying on a high input of pesticides and showing low ecosystem functioning and
      an agroecosystem with low inputs, relying on a high functioning of the ecosystem.
      From the production point of view, no type of management clearly outclassed the
      other and their ranking depended on the type of pesticide used. From the
      robustness point of view, the two types of managements performed differently when
      subjected to different types of perturbations. Ecologically intensive systems
      were more robust to pest outbreaks and perturbations related to pesticide
      characteristics while chemically intensive systems were more robust to Cacao
      production and management-related perturbation.

PMID- 24312470
TI  - Retro-inverso carbohydrate mimetic peptides with annexin1-binding selectivity,
      are stable in vivo, and target tumor vasculature.
AB  - Previous research suggests that carbohydrate mimetic peptide IF7 (IFLLWQR) has an
      excellent targeting property to annexin1 (Anxa1), a specific marker on the tumor
      endothelium. However, IF7 is susceptible to proteolysis and has a poor stability
      in vivo. We prepared a D-amino acid, reverse sequence peptide of IF7, designated
      RIF7, to confer protease resistance while retaining bioactivity. Experimental
      results indicate that RIF7 had significantly increased stability and an increased
      receptor binding affinity than IF7, and this new moiety may represent a
      clinically relevant vehicle for anticancer drugs. 

PMID- 24312471
TI  - The basal nodosaurid ankylosaur Europelta carbonensis n. gen., n. sp. from the
      Lower Cretaceous (lower Albian) Escucha Formation of northeastern Spain.
AB  - Nodosaurids are poorly known from the Lower Cretaceous of Europe. Two associated
      ankylosaur skeletons excavated from the lower Albian carbonaceous member of the
      Escucha Formation near Arino in northeastern Teruel, Spain reveal nearly all the
      diagnostic recognized character that define nodosaurid ankylosaurs. These new
      specimens comprise a new genus and species of nodosaurid ankylosaur and represent
      the single most complete taxon of ankylosaur from the Cretaceous of Europe. These
      two specimens were examined and compared to all other known ankylosaurs.
      Comparisons of these specimens document that Europelta carbonensis n. gen., n.
      sp. is a nodosaur and is the sister taxon to the Late Cretaceous nodosaurids
      Anoplosaurus, Hungarosaurus, and Struthiosaurus, defining a monophyletic clade of
      European nodosaurids- the Struthiosaurinae. 

PMID- 24312473
TI  - Mechanical stress impairs mitosis progression in multi-cellular tumor spheroids.
AB  - Growing solid tumors are subjected to mechanical stress that influences their
      growth rate and development. However, little is known about its effects on tumor
      cell biology. To explore this issue, we investigated the impact of mechanical
      confinement on cell proliferation in MultiCellular Tumor Spheroids (MCTS), a 3D
      culture model that recapitulates the microenvironment, proliferative gradient,
      and cell-cell interactions of a tumor. Dedicated polydimethylsiloxane (PDMS)
      microdevices were designed to spatially restrict MCTS growth. In this confined
      environment, spheroids are likely to experience mechanical stress as indicated by
      their modified cell morphology and density and by their relaxation upon removal
      from the microdevice. We show that the proliferation gradient within mechanically
      confined spheroids is different in comparison to MCTS grown in suspension.
      Furthermore, we demonstrate that a population of cells within the body of
      mechanically confined MCTS is arrested at mitosis. Cell morphology analysis
      reveals that this mitotic arrest is not caused by impaired cell rounding, but
      rather that confinement negatively affects bipolar spindle assembly. All together
      these results suggest that mechanical stress induced by progressive confinement
      of growing spheroids could impair mitotic progression. This study paves the way
      to future research to better understand the tumor cell response to mechanical
      cues similar to those encountered during in vivo tumor development. 

PMID- 24312474
TI  - A numerical study of local variations in tidal regime of Tagus estuary, Portugal.
AB  - Tidal dynamics of shallow estuaries and lagoons is a complex matter that has
      attracted the attention of a large number of researchers over the last few
      decades. The main purpose of the present work is to study the intricate tidal
      dynamics of the Tagus estuary, which states as the largest estuary of the Iberian
      Peninsula and one of the most important wetlands in Portugal and Europe. Tagus
      has large areas of low depth and a remarkable geomorphology, both determining the
      complex propagation of tidal waves along the estuary of unknown manner. A non
      linear two-dimensional vertically integrated hydrodynamic model was considered to
      be adequate to simulate its hydrodynamics and an application developed from the
      SIMSYS2D model was applied to study the tidal propagation along the estuary. The
      implementation and calibration of this model revealed its accuracy to predict
      tidal properties along the entire system. Several model runs enabled the analysis
      of the local variations in tidal dynamics, through the interpretation of
      amplitude and phase patterns of the main tidal constituents, tidal asymmetry,
      tidal ellipses, form factor and tidal dissipation. Results show that Tagus
      estuary tidal dynamics is extremely dependent on an estuarine resonance mode for
      the semi-diurnal constituents that induce important tidal characteristics.
      Besides, the estuarine coastline features and topography determines the changes
      in tidal propagation along the estuary, which therefore result essentially from a
      balance between convergence/divergence and friction and advection effects,
      besides the resonance effects. 

PMID- 24312472
TI  - Decoupling polarization of the Golgi apparatus and GM1 in the plasma membrane.
AB  - Cell polarization is a process of coordinated cellular rearrangements that
      prepare the cell for migration. GM1 is synthesized in the Golgi apparatus and
      localized in membrane microdomains that appear at the leading edge of polarized
      cells, but the mechanism by which GM1 accumulates asymmetrically is unknown. The
      Golgi apparatus itself becomes oriented toward the leading edge during cell
      polarization, which is thought to contribute to plasma membrane asymmetry. Using
      quantitative image analysis techniques, we measure the extent of polarization of
      the Golgi apparatus and GM1 in the plasma membrane simultaneously in individual
      cells subject to a wound assay. We find that GM1 polarization starts just 10 min
      after stimulation with growth factors, while Golgi apparatus polarization takes
      30 min. Drugs that block Golgi polarization or function have no effect on GM1
      polarization, and, conversely, inhibiting GM1 polarization does not affect Golgi
      apparatus polarization. Evaluation of Golgi apparatus and GM1 polarization in
      single cells reveals no correlation between the two events. Our results indicate
      that Golgi apparatus and GM1 polarization are controlled by distinct
      intracellular cascades involving the Ras/Raf/MEK/ERK and the PI3K/Akt/mTOR
      pathways, respectively. Analysis of cell migration and invasion suggest that
      MEK/ERK activation is crucial for two dimensional migration, while PI3K
      activation drives three dimensional invasion, and no cumulative effect is
      observed from blocking both simultaneously. The independent biochemical control
      of GM1 polarity by PI3K and Golgi apparatus polarity by MEK/ERK may act
      synergistically to regulate and reinforce directional selection in cell
      migration. 

PMID- 24312475
TI  - Carcinoma initiation via RB tumor suppressor inactivation: a versatile approach
      to epithelial subtype-dependent cancer initiation in diverse tissues.
AB  - Carcinomas arise in a complex microenvironment consisting of multiple distinct
      epithelial lineages surrounded by a variety of stromal cell types. Understanding
      cancer etiologies requires evaluating the relationship among cell types during
      disease initiation and through progression. Genetically engineered mouse (GEM)
      models facilitate the prospective examination of early oncogenic events, which is
      not possible in humans. Since most solid tumors harbor aberrations in the RB
      network, we developed an inducible GEM approach for the establishment and
      assessment of carcinoma initiation in a diverse range of epithelial tissues and
      subtypes upon inactivation of RB-mediated tumor suppression (RB-TS). The system
      allows independent assessment of epithelial subtypes that express either
      cytokeratins (K) 18 or 19. By Cre-dependent expression of a protein that
      dominantly inactivates RB and functionally redundant proteins p107 and p130,
      neoplasia could be initiated in either K18 or K19 expressing cells of numerous
      tissues. By design, because only a single pathway aberration was engineered,
      carcinomas developed stochastically only after long latency. Hence, this system,
      which allows for directed cell type-specific carcinoma initiation, facilitates
      further definition of events that can progress neoplasms to aggressive cancers
      via engineered, carcinogen-induced and/or spontaneous evolution. 

PMID- 24312476
TI  - Eggshell appearance does not signal maternal corticosterone exposure in Japanese
      quail: an experimental study with brown-spotted eggs.
AB  - Reproduction is a critical period for birds as they have to cope with many
      stressful events. One consequence of an acute exposure to stress is the release
      of corticosterone, the avian stress hormone. Prolonged stress can have negative
      impacts on the immune system, resulting in, for example, increased oxidative
      stress. Through maternal effects, females are known to modulate their investment
      in eggs content according to their own physiological condition. Less is known
      about maternal investment in eggshells, especially in pigments. The two main
      eggshell pigments may possess opposite antioxidant properties: protoporphyrin
      (brown) is a pro-oxidant, whereas biliverdin (blue-green) is an antioxidant. In
      Japanese quail, we know that the deposition of both pigments is related to female
      body condition. Thus, a chronic stress response may be reflected in eggshell
      coloration. Using female Japanese quails that lay brown-spotted eggs, we explored
      whether physiological exposure to corticosterone induces a change in female basal
      stress and antioxidant factors, and eggshell pigment concentration,
      spectrophotometric reflectance, and maculation coverage. We supplemented adult
      females over a 2 week period with either peanut oil (control) or corticosterone
      (treatment). We collected pre- and post-supplementation eggs and analysed the
      effect of corticosterone treatment on female physiology and eggshell appearance
      parameters. Except for corticosterone-fed birds which laid eggs with brighter
      spots, supplementation had no significant effect on female physiology or eggshell
      pigment concentration, reflectance and maculation. The change in eggshell spot
      brightness was not detected by a photoreceptor noise-limited color opponent model
      of avian visual perception. Our data confirms that eggshell reflectance in
      spotted eggs varies over the laying sequence, and spot reflectance may be a key
      factor that is affected by females CORT exposure, even if the changes are not
      detected by an avian visual model. 

PMID- 24312477
TI  - Exploring the impact of target eccentricity and task difficulty on covert visual
      spatial attention and its implications for brain computer interfacing.
AB  - OBJECTIVE: Covert visual spatial attention is a relatively new task used in brain
      computer interfaces (BCIs) and little is known about the characteristics which
      may affect performance in BCI tasks. We investigated whether eccentricity and
      task difficulty affect alpha lateralization and BCI performance. APPROACH: We
      conducted a magnetoencephalography study with 14 participants who performed a
      covert orientation discrimination task at an easy or difficult stimulus contrast
      at either a near (3.5 degrees ) or far (7 degrees ) eccentricity. Task difficulty
      was manipulated block wise and subjects were aware of the difficulty level of
      each block. MAIN RESULTS: Grand average analyses revealed a significantly larger
      hemispheric lateralization of posterior alpha power in the difficult condition
      than in the easy condition, while surprisingly no difference was found for
      eccentricity. The difference between task difficulty levels was significant in
      the interval between 1.85 s and 2.25 s after cue onset and originated from a
      stronger decrease in the contralateral hemisphere. No significant effect of
      eccentricity was found. Additionally, single-trial classification analysis
      revealed a higher classification rate in the difficult (65.9%) than in the easy
      task condition (61.1%). No effect of eccentricity was found in classification
      rate. SIGNIFICANCE: Our results indicate that manipulating the difficulty of a
      task gives rise to variations in alpha lateralization and that using a more
      difficult task improves covert visual spatial attention BCI performance. The
      variations in the alpha lateralization could be caused by different factors such
      as an increased mental effort or a higher visual attentional demand. Further
      research is necessary to discriminate between them. We did not discover any
      effect of eccentricity in contrast to results of previous research.

PMID- 24312478
TI  - Knowledge and theme discovery across very large biological data sets using
      distributed queries: a prototype combining unstructured and structured data.
AB  - As the discipline of biomedical science continues to apply new technologies
      capable of producing unprecedented volumes of noisy and complex biological data,
      it has become evident that available methods for deriving meaningful information
      from such data are simply not keeping pace. In order to achieve useful results,
      researchers require methods that consolidate, store and query combinations of
      structured and unstructured data sets efficiently and effectively. As we move
      towards personalized medicine, the need to combine unstructured data, such as
      medical literature, with large amounts of highly structured and high-throughput
      data such as human variation or expression data from very large cohorts, is
      especially urgent. For our study, we investigated a likely biomedical query using
      the Hadoop framework. We ran queries using native MapReduce tools we developed as
      well as other open source and proprietary tools. Our results suggest that the
      available technologies within the Big Data domain can reduce the time and effort
      needed to utilize and apply distributed queries over large datasets in practical
      clinical applications in the life sciences domain. The methodologies and
      technologies discussed in this paper set the stage for a more detailed evaluation
      that investigates how various data structures and data models are best mapped to
      the proper computational framework. 

PMID- 24312479
TI  - TAS2R38 and its influence on smoking behavior and glucose homeostasis in the
      German Sorbs.
AB  - BACKGROUND: Genetic variants within the bitter taste receptor gene TAS2R38 are
      associated with sensitivity to bitter taste and are related to eating behavior in
      the Amish population. Sensitivity to bitter taste is further related to
      anthropometric traits in an genetically isolated Italian population. We tested
      whether the TAS2R38 variants (rs713598; rs1726866 and rs10246939) may be related
      to eating behavior, anthropometric parameters, metabolic traits and consumer
      goods intake in the German Sorbs. MATERIALS AND METHODS: The three SNPs were
      genotyped in a total cohort of 1007 individuals (male/female: 405/602). The
      German version of the three-factor eating questionnaire was completed by 548
      individuals. Genetic association analyses for smoking behavior, alcohol and
      coffee intake, eating behavior factors (restraint, disinhibition and hunger) and
      other metabolic traits were analyzed. Further, by combining the three SNPs we
      applied comparative haplotype analyses categorizing PAV (proline-alanine-valine)
      carriers (tasters) vs. homozygous AVI (alanin-valine-isoleucine) carriers (non
      tasters). RESULTS: Significant associations of genetic variants within TAS2R38
      were identified with percentage of body fat, which were driven by associations in
      women. In men, we observed significant associations with 30 min plasma glucose,
      and area under the curve for plasma glucose (0-120 min) (all adjusted P<=0.05).
      Further, we found that carriers of at least one PAV allele show significantly
      lower cigarette smoking per day (P = 0.002) as well as, albeit non-significant,
      lower alcohol intake. We did not confirm previously reported associations between
      genetic variants of TAS2R38 and eating behavior. CONCLUSION: Our data suggest
      that genetic variation in TAS2R38 is related to individual body composition
      measures and may further influence consumer goods intake in the Sorbs possibly
      via individual sensitivity to bitter taste.

PMID- 24312480
TI  - Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated
      derivatives inhibits soybean root growth.
AB  - Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and
      sinapic acids) are known allelochemicals that affect the seed germination and
      root growth of many plant species. Recent studies have indicated that the
      reduction of root growth by these allelochemicals is associated with premature
      cell wall lignification. We hypothesized that an influx of these compounds into
      the phenylpropanoid pathway increases the lignin monomer content and reduces the
      root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p
      coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and
      the composition of p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) monomers.
      To this end, three-day-old seedlings were cultivated in nutrient solution with or
      without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid
      pathway) in a growth chamber for 24 h. In general, the results showed that 1)
      cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased
      lignin content; 2) cinnamic and p-coumaric acids increased p-hydroxyphenyl (H)
      monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl
      (G) content, and sinapic acid increased sinapyl (S) content; 3) when applied in
      conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4
      hydroxylase, C4H), cinnamic acid reduced H, G and S contents; and 4) when applied
      in conjunction with 3,4-(methylenedioxy)cinnamic acid (MDCA, an inhibitor of the
      4-coumarate:CoA ligase, 4CL), p-coumaric acid reduced H, G and S contents,
      whereas caffeic, ferulic and sinapic acids reduced G and S contents. These
      results confirm our hypothesis that exogenously applied allelochemicals are
      channeled into the phenylpropanoid pathway causing excessive production of lignin
      and its main monomers. By consequence, an enhanced stiffening of the cell wall
      restricts soybean root growth. 

PMID- 24312481
TI  - Computational prediction of broadly neutralizing HIV-1 antibody epitopes from
      neutralization activity data.
AB  - Broadly neutralizing monoclonal antibodies effective against the majority of
      circulating isolates of HIV-1 have been isolated from a small number of infected
      individuals. Definition of the conformational epitopes on the HIV spike to which
      these antibodies bind is of great value in defining targets for vaccine and drug
      design. Drawing on techniques from compressed sensing and information theory, we
      developed a computational methodology to predict key residues constituting the
      conformational epitopes on the viral spike from cross-clade neutralization
      activity data. Our approach does not require the availability of structural
      information for either the antibody or antigen. Predictions of the conformational
      epitopes of ten broadly neutralizing HIV-1 antibodies are shown to be in good
      agreement with new and existing experimental data. Our findings suggest that our
      approach offers a means to accelerate epitope identification for diverse
      pathogenic antigens. 

PMID- 24312482
TI  - Identification of QTLs associated with oil content in a high-oil Brassica napus
      cultivar and construction of a high-density consensus map for QTLs comparison in
      B. napus.
AB  - Increasing seed oil content is one of the most important goals in breeding of
      rapeseed (B. napus L.). To dissect the genetic basis of oil content in B. napus,
      a large and new double haploid (DH) population containing 348 lines was obtained
      from a cross between 'KenC-8' and 'N53-2', two varieties with >10% difference in
      seed oil content, and this population was named the KN DH population. A genetic
      linkage map consisting of 403 markers was constructed, which covered a total
      length of 1783.9 cM with an average marker interval of 4.4 cM. The KN DH
      population was phenotyped in eight natural environments and subjected to
      quantitative trait loci (QTL) analysis for oil content. A total of 63 identified
      QTLs explaining 2.64-17.88% of the phenotypic variation were identified, and
      these QTLs were further integrated into 24 consensus QTLs located on 11
      chromosomes using meta-analysis. A high-density consensus map with 1335 marker
      loci was constructed by combining the KN DH map with seven other published maps
      based on the common markers. Of the 24 consensus QTLs in the KN DH population, 14
      were new QTLs including five new QTLs in A genome and nine in C genome. The
      analysis revealed that a larger population with significant differences in oil
      content gave a higher power detecting new QTLs for oil content, and the
      construction of the consensus map provided a new clue for comparing the QTLs
      detected in different populations. These findings enriched our knowledge of QTLs
      for oil content and should be a potential in marker-assisted breeding of B.
      napus. 

PMID- 24312483
TI  - Transdifferentiation of adipose-derived stem cells into keratinocyte-like cells:
      engineering a stratified epidermis.
AB  - Skin regeneration is an important area of research in the field of tissue
      engineering, especially for cases involving loss of massive areas of skin, where
      current treatments are not capable of inducing permanent satisfying replacements.
      Human adipose-derived stem cells (ASC) have been shown to differentiate in-vitro
      into both mesenchymal lineages and non-mesenchymal lineages, confirming their
      transdifferentiation ability. This versatile differentiation potential, coupled
      with their ease of harvest, places ASC at the advancing front of stem cell-based
      therapies. In this study, we hypothesized that ASC also have the capacity to
      transdifferentiate into keratinocyte-like cells and furthermore are able to
      engineer a stratified epidermis. ASC were successfully isolated from
      lipoaspirates and cell sorted (FACS). After sorting, ASC were either co-cultured
      with human keratinocytes or with keratinocyte conditioned media. After a 14-day
      incubation period, ASC developed a polygonal cobblestone shape characteristic of
      human keratinocytes. Western blot and q-PCR analysis showed the presence of
      specific keratinocyte markers including cytokeratin-5, involucrin, filaggrin and
      stratifin in these keratinocyte-like cells (KLC); these markers were absent in
      ASC. To further evaluate if KLC were capable of stratification akin to human
      keratinocytes, ASC were seeded on top of human decellularized dermis and cultured
      in the presence or absence of EGF and high Ca(2+) concentrations. Histological
      analysis demonstrated a stratified structure similar to that observed in normal
      skin when cultured in the presence of EGF and high Ca(2+). Furthermore,
      immunohistochemical analysis revealed the presence of keratinocyte markers such
      as involucrin, cytokeratin-5 and cytokeratin-10. In conclusion this study
      demonstrates for the first time that ASC have the capacity to transdifferentiate
      into KLC and engineer a stratified epidermis. This study suggests that adipose
      tissue is potentially a readily available and accessible source of keratinocytes,
      particularly for severe wounds encompassing large surface areas of the body and
      requiring prompt epithelialization. 

PMID- 24312484
TI  - Factors associated with knowledge of diabetes in patients with type 2 diabetes
      using the Diabetes Knowledge Test validated with Rasch analysis.
AB  - OBJECTIVE: In patients with Type 2 diabetes, to determine the factors associated
      with diabetes knowledge, derived from Rasch analysis, and compare results with a
      traditional raw scoring method. RESEARCH DESIGN & METHODS: Participants in this
      cross-sectional study underwent a comprehensive clinical and biochemical
      assessment. Diabetes knowledge (main outcome) was assessed using the Diabetes
      Knowledge Test (DKT) which was psychometrically validated using Rasch analysis.
      The relationship between diabetes knowledge and risk factors identified during
      univariate analyses was examined using multivariable linear regression. The
      results using raw and Rasch-transformed methods were descriptively compared.
      RESULTS: 181 patients (mean age+/-standard deviation = 66.97+/-9.17 years; 113
      (62%) male) were included. Using Rasch-derived DKT scores, those with greater
      education (beta = 1.14; CI: 0.25,2.04, p = 0.013); had seen an ophthalmologist
      (beta = 1.65; CI: 0.63,2.66, p = 0.002), and spoke English at home (beta = 1.37;
      CI: 0.43,2.31, p = 0.005) had significantly better diabetes knowledge than those
      with less education, had not seen an ophthalmologist and spoke a language other
      than English, respectively. Patients who were members of the National Diabetes
      Service Scheme (NDSS) and had seen a diabetes educator also had better diabetes
      knowledge than their counterparts. Higher HbA1c level was independently
      associated with worse diabetes knowledge. Using raw measures, access to an
      ophthalmologist and NDSS membership were not independently associated with
      diabetes knowledge. CONCLUSIONS: Sociodemographic, clinical and service use
      factors were independently associated with diabetes knowledge based on both raw
      scores and Rasch-derived scores, which supports the implementation of targeted
      interventions to improve patients' knowledge. Choice of psychometric analytical
      method can affect study outcomes and should be considered during intervention
      development.

PMID- 24312485
TI  - Calf-level factors associated with bovine neonatal pancytopenia--a multi-country
      case-control study.
AB  - Bovine neonatal pancytopenia (BNP), a high fatality condition causing
      haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in
      Germany and subsequently observed at low incidence in other European countries
      and New Zealand. A multi-country matched case-control study was conducted in 2011
      to identify calf-level risk factors for BNP. 405 BNP cases were recruited from
      330 farms in Belgium, France, Germany and the Netherlands by laboratory
      confirmation of farmer-reported cases. Up to four calves of similar age from the
      same farm were selected as controls (1154 calves). Risk factor data were
      collected by questionnaire. Multivariable modelling using conditional logistic
      regression indicated that PregSure(r)BVD (PregSure, Pfizer Animal Health)
      vaccination of the dam was strongly associated with BNP cases (adjusted matched
      Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval - ci 2.4,
      134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were
      more likely to have a case than first lactation vaccinated dams (amOR 2.2 second
      lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8;
      p = <0.001). Feeding colostrum from other cows was strongly associated with BNP
      if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but
      the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p
      = 0.024). Feeding exclusively dam's milk was a higher risk than other types of
      milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions
      were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for
      feeding other cows' colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam's milk.
      No other calf-level factors were identified, suggesting that there are other
      important factors that are outside the scope of this study, such as genetics,
      which explain why BNP develops in some PregSure-colostrum-exposed calves but not
      in others. 

PMID- 24312486
TI  - Evaluation of the stability, bioavailability, and hypersensitivity of the omega-3
      derived anti-leukemic prostaglandin: Delta(12)-prostaglandin J3.
AB  - Previous studies have demonstrated the ability of an eicosapentaenoic acid (EPA)
      derived endogenous cyclopentenone prostaglandin (CyPG) metabolite, Delta(12)
      PGJ3, to selectively target leukemic stem cells, but not the normal hematopoietic
      stems cells, in in vitro and in vivo models of chronic myelogenous leukemia
      (CML). Here we evaluated the stability, bioavailability, and hypersensitivity of
      Delta(12)-PGJ3. The stability of Delta(12)-PGJ3 was evaluated under simulated
      conditions using artificial gastric and intestinal juice. The bioavailability of
      Delta(12)-PGJ3 in systemic circulation was demonstrated upon intraperitoneal
      injection into mice by LC-MS/MS. Delta(12)-PGJ3 being a downstream metabolite of
      PGD3 was tested in vitro using primary mouse bone marrow-derived mast cells
      (BMMCs) and in vivo mouse models for airway hypersensitivity. ZK118182, a
      synthetic PG analog with potent PGD2 receptor (DP)-agonist activity and a drug
      candidate in current clinical trials, was used for toxicological comparison.
      Delta(12)-PGJ3 was relatively more stable in simulated gastric juice than in
      simulated intestinal juice that followed first-order kinetics of degradation.
      Intraperitoneal injection into mice revealed that Delta(12)-PGJ3 was bioavailable
      and well absorbed into systemic circulation with a Cmax of 263 ug/L at 12 h.
      Treatment of BMMCs with ZK118182 for 12 h resulted in increased production of
      histamine, while Delta(12)-PGJ3 did not induce degranulation in BMMCs nor
      increase histamine. In addition, in vivo testing for hypersensitivity in mice
      showed that ZK118182 induces higher airways hyperresponsiveness when compared
      Delta(12)-PGJ3 and/or PBS control. Based on the stability studies, our data
      indicates that intraperitoneal route of administration of Delta(12)-PGJ3 was
      favorable than oral administration to achieve effective pharmacological levels in
      the plasma against leukemia. Delta(12)-PGJ3 failed to increase histamine and IL-4
      in BMMCs, which is in agreement with reduced airway hyperresponsiveness in mice.
      In summary, our studies suggest Delta(12)-PGJ3 to be a promising bioactive
      metabolite for further evaluation as a potential drug candidate for treating CML.

PMID- 24312487
TI  - MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells.
AB  - The miR-99 family is one of the evolutionarily most ancient microRNA families,
      and it plays a critical role in developmental timing and the maintenance of
      tissue identity. Recent studies, including reports from our group, suggested that
      the miR-99 family regulates various physiological processes in adult tissues,
      such as dermal wound healing, and a number of disease processes, including
      cancer. By combining 5 independent genome-wide expression profiling experiments,
      we identified a panel of 266 unique transcripts that were down-regulated in
      epithelial cells transfected with miR-99 family members. A comprehensive
      bioinformatics analysis using 12 different sequence-based microRNA target
      prediction algorithms revealed that 81 out of these 266 down-regulated
      transcripts are potential direct targets for the miR-99 family. Confirmation
      experiments and functional analyses were performed to further assess 6 selected
      miR-99 target genes, including mammalian Target of rapamycin (mTOR), Homeobox A1
      (HOXA1), CTD small phosphatase-like (CTDSPL), N-myristoyltransferase 1 (NMT1),
      Transmembrane protein 30A (TMEM30A), and SWI/SNF-related matrix-associated actin
      dependent regulator of chromatin subfamily A member 5 (SMARCA5). HOXA1 is a known
      proto-oncogene, and it also plays an important role in embryonic development. The
      direct targeting of the miR-99 family to two candidate binding sequences located
      in the HOXA1 mRNA was confirmed using a luciferase reporter gene assay and a
      ribonucleoprotein-immunoprecipitation (RIP-IP) assay. Ectopic transfection of miR
      99 family reduced the expression of HOXA1, which, in consequence, down-regulated
      the expression of its downstream gene (i.e., Bcl-2) and led to reduced
      proliferation and cell migration, as well as enhanced apoptosis. In summary, we
      identified a number of high-confidence miR-99 family target genes, including
      proto-oncogene HOXA1, which may play an important role in regulating epithelial
      cell proliferation and migration during physiological disease processes, such as
      dermal wound healing and tumorigenesis. 

PMID- 24312489
TI  - A simple method for assessing free brain/free plasma ratios using an in vitro
      model of the blood brain barrier.
AB  - Historically, the focus has been to use in vitro BBB models to optimize rate of
      drug delivery to the CNS, whereas total in vivo brain/plasma ratios have been
      used for optimizing extent. However, these two parameters do not necessarily show
      good correlations with receptor occupancy data or other pharmacological readouts.
      In line with the free drug hypothesis, the use of unbound brain concentrations
      (Cu,br) has been shown to provide the best correlations with pharmacological
      data. However, typically the determination of this parameter requires
      microdialysis, a technique not ideally suited for screening in early drug
      development. Alternative, and less resource-demanding methodologies to determine
      Cu,br employ either equilibrium dialysis of brain homogenates or incubations of
      brain slices in buffer to determine fraction unbound brain (fu,br), which is
      subsequently multiplied by the total brain concentration to yield Cu,br. To
      determine Cu,br/Cu,pl ratios this way, still requires both in vitro and in vivo
      experiments that are quite time consuming. The main objective of this study was
      to explore the possibility to directly generate Cu,br/Cu,pl ratios in a single in
      vitro model of the BBB, using a co-culture of brain capillary endothelial and
      glial cells in an attempt to mimick the in vivo situation, thereby greatly
      simplifying existing experimental procedures. Comparison to microdialysis brain
      concentration profiles demonstrates the possibility to estimate brain exposure
      over time in the BBB model. A stronger correlation was found between in vitro
      Cu,br/Cu,pl ratios and in vivo Cu,br/Cu,pl obtained using fu,br from brain slice
      than with fu,br from brain homogenate for a set of 30 drugs. Overall, Cu,br/Cu,pl
      ratios were successfully predicted in vitro for 88% of the 92 studied compounds.
      This result supports the possibility to use this methodology for identifying
      compounds with a desirable in vivo response in the CNS early on in the drug
      discovery process. 

PMID- 24312490
TI  - Co-evolution of the mating position and male genitalia in insects: a case study
      of a hangingfly.
AB  - Hangingflies are unique for the male providing a nuptial gift to the female
      during mating and taking a face-to-face hanging copulation with the female. Their
      male genitalia are peculiar for an extremely elongated penisfilum, a pair of well
      developed epandrial lobes (9th tergum), and a pair of degenerated gonostyli.
      However, the co-evolution of their face-to-face copulation behavior and the male
      genitalia has rarely been studied hitherto. In this paper the mating behavior of
      the hangingfly Bittacus planus Cheng, 1949 was observed under laboratory
      conditions, and the morphology of the male and female external genitalia was
      investigated using light and scanning electron microscopy. The male provides an
      insect prey as a nuptial gift to the female in courtship and mating process, and
      commits a face-to-face copulation. During copulation, the male abdomen twists
      temporarily about 180 degrees  to accommodate their face-to-face mating position.
      The aedeagal complex has an extremely elongated penisfilum, corresponding to the
      elongated spermathecal duct of the female. The well-developed epandrial lobes
      serve as claspers to grasp the female subgenital plate during copulation,
      replacing the function of gonostyli, which are greatly reduced in Bittacidae. The
      modified proctiger assists the penisfilum to stretch and to enter into the female
      spermathecal duct. The possible reasons why this species might mate face-to-face
      are briefly discussed. 

PMID- 24312488
TI  - Understanding patients' adherence-related beliefs about medicines prescribed for
      long-term conditions: a meta-analytic review of the Necessity-Concerns Framework.
AB  - BACKGROUND: Patients' beliefs about treatment influence treatment engagement and
      adherence. The Necessity-Concerns Framework postulates that adherence is
      influenced by implicit judgements of personal need for the treatment (necessity
      beliefs) and concerns about the potential adverse consequences of taking it.
      OBJECTIVE: To assess the utility of the NCF in explaining nonadherence to
      prescribed medicines. DATA SOURCES: We searched EMBASE, Medline, PsycInfo,
      CDSR/DARE/CCT and CINAHL from January 1999 to April 2013 and handsearched
      reference sections from relevant articles. STUDY ELIGIBILITY CRITERIA: Studies
      using the Beliefs about Medicines Questionnaire (BMQ) to examine perceptions of
      personal necessity for medication and concerns about potential adverse effects,
      in relation to a measure of adherence to medication. PARTICIPANTS: Patients with
      long-term conditions. STUDY APPRAISAL AND SYNTHESIS METHODS: Systematic review
      and meta-analysis of methodological quality was assessed by two independent
      reviewers. We pooled odds ratios for adherence using random effects models.
      RESULTS: We identified 3777 studies, of which 94 (N = 25,072) fulfilled the
      inclusion criteria. Across studies, higher adherence was associated with stronger
      perceptions of necessity of treatment, OR = 1.742, 95% CI [1.569, 1.934],
      p<0.0001, and fewer Concerns about treatment, OR = 0.504, 95% CI: [0.450, 0.564],
      p<0.0001. These relationships remained significant when data were stratified by
      study size, the country in which the research was conducted and the type of
      adherence measure used. LIMITATIONS: Few prospective longitudinal studies using
      objective adherence measures were identified. CONCLUSIONS: The Necessity-Concerns
      Framework is a useful conceptual model for understanding patients' perspectives
      on prescribed medicines. Taking account of patients' necessity beliefs and
      concerns could enhance the quality of prescribing by helping clinicians to engage
      patients in treatment decisions and support optimal adherence to appropriate
      prescriptions.

PMID- 24312491
TI  - A balanced IL-1beta activity is required for host response to Citrobacter
      rodentium infection.
AB  - Microbial sensing plays essential roles in the innate immune response to
      pathogens. In particular, NLRP3 forms a multiprotein inflammasome complex
      responsible for the maturation of interleukin (IL)-1beta. Our aim was to
      delineate the role of the NLRP3 inflammasome in macrophages, and the contribution
      of IL-1beta to the host defense against Citrobacter rodentium acute infection in
      mice. Nlrp3(-/-) and background C57BL/6 (WT) mice were infected by orogastric
      gavage, received IL-1beta (0.5 ug/mouse; ip) on 0, 2, and 4 days post-infection
      (DPI), and assessed on 6 and 10 DPI. Infected Nlrp3(-/-) mice developed severe
      colitis; IL-1beta treatments reduced colonization, abrogated dissemination of
      bacteria to mesenteric lymph nodes, and protected epithelial integrity of
      infected Nlrp3(-/-) mice. In contrast, IL-1beta treatments of WT mice had an
      opposite effect with increased penetration of bacteria and barrier disruption.
      Microscopy showed reduced damage in Nlrp3(-/-) mice, and increased severity of
      disease in WT mice with IL-1beta treatments, in particular on 10 DPI. Secretion
      of some pro-inflammatory plasma cytokines was dissipated in Nlrp3(-/-) compared
      to WT mice. IL-1beta treatments elevated macrophage infiltration into infected
      crypts in Nlrp3(-/-) mice, suggesting that IL-1beta may improve macrophage
      function, as exogenous administration of IL-1beta increased phagocytosis of C.
      rodentium by peritoneal Nlrp3(-/-) macrophages in vitro. As well, the exogenous
      administration of IL-1beta to WT peritoneal macrophages damaged the epithelial
      barrier of C. rodentium-infected polarized CMT-93 cells. Treatment of Nlrp3(-/-)
      mice with IL-1beta seems to confer protection against C. rodentium infection by
      reducing colonization, protecting epithelial integrity, and improving macrophage
      activity, while extraneous IL-1beta appeared to be detrimental to WT mice.
      Together, these findings highlight the importance of balanced cytokine responses
      as IL-1beta improved bacterial clearance in Nlrp3(-/-) mice but increased tissue
      damage when given to WT mice. 

PMID- 24312492
TI  - Reversal of ophthalmic artery flow and stroke outcomes in Asian patients with
      acute ischemic stroke and unilateral severe cervical carotid stenosis.
AB  - BACKGROUND: The aim of this study was to assess the clinical implications of
      reversed ophthalmic artery flow (ROAF) for stroke risk and outcomes in subjects
      with unilateral severe cervical carotid stenosis/occlusion. METHODS: We
      investigated 128 subjects (101 with acute stroke and 27 without), selected from a
      large hospital patients base (n  =  14,701), identified with unilateral high
      grade cervical carotid stenosis/occlusion by using duplex ultrasonography and
      brain magnetic resonance imaging. All clinical characteristics were compared for
      stroke risk between acute stroke and nonstroke groups. Patients with acute stroke
      were divided into 4 subgroups according to ophthalmic artery flow direction and
      intracranial stenosis severity, and stroke outcomes were evaluated. RESULTS: The
      acute stroke group had significantly higher percentages of ROAF (52.5%, p  = 
      0.003), carotid occlusion (33.7%, p  =  0.046), and severe intracranial stenosis
      (74.3%, p<0.001). However, multivariate analysis demonstrated that intracranial
      stenosis was the only significant risk factor (odds ratio  =  10.38; 95%
      confidence interval  =  3.64-29.65; p<0.001). Analysis of functional outcomes
      among the 4 subgroups of patients with stroke showed significant trends (p  = 
      0.018 to 0.001) for better stroke outcomes from ROAF and mild or no intracranial
      stenosis. ROAF improved 10-20% stroke outcomes, as compared to forward ophthalmic
      artery flow, among the patients with stroke and the same degree of severities of
      intracranial stenosis. CONCLUSIONS: Patients with acute stroke and severe
      unilateral cervical carotid stenosis/occlusion significantly have high incidence
      of intracranial stenosis and ROAF. Intracranial stenosis is a major stroke risk
      indicator as well as a predictor for worse stroke outcomes, and ROAF may provide
      partial compensation for improving stroke outcomes.

PMID- 24312493
TI  - Landscape patterns in rainforest phylogenetic signal: isolated islands of refugia
      or structured continental distributions?
AB  - OBJECTIVES: Identify patterns of change in species distributions, diversity,
      concentrations of evolutionary history, and assembly of Australian rainforests.
      METHODS: We used the distribution records of all known rainforest woody species
      in Australia across their full continental extent. These were analysed using
      measures of species richness, phylogenetic diversity (PD), phylogenetic endemism
      (PE) and phylogenetic structure (net relatedness index; NRI). Phylogenetic
      structure was assessed using both continental and regional species pools. To test
      the influence of growth-form, freestanding and climbing plants were analysed
      independently, and in combination. RESULTS: Species richness decreased along two
      generally orthogonal continental axes, corresponding with wet to seasonally dry
      and tropical to temperate habitats. The PE analyses identified four main areas of
      substantially restricted phylogenetic diversity, including parts of Cape York,
      Wet Tropics, Border Ranges, and Tasmania. The continental pool NRI results showed
      evenness (species less related than expected by chance) in groups of grid cells
      in coastally aligned areas of species rich tropical and sub-tropical rainforest,
      and in low diversity moist forest areas in the south-east of the Great Dividing
      Range and in Tasmania. Monsoon and drier vine forests, and moist forests inland
      from upland refugia showed phylogenetic clustering, reflecting lower diversity
      and more relatedness. Signals for evenness in Tasmania and clustering in northern
      monsoon forests weakened in analyses using regional species pools. For climbing
      plants, values for NRI by grid cell showed strong spatial structuring, with high
      diversity and PE concentrated in moist tropical and subtropical regions.
      CONCLUSIONS/SIGNIFICANCE: Concentrations of rainforest evolutionary history
      (phylo-diversity) were patchily distributed within a continuum of species
      distributions. Contrasting with previous concepts of rainforest community
      distribution, our findings of continuous distributions and continental
      connectivity have significant implications for interpreting rainforest
      evolutionary history and current day ecological processes, and for managing
      rainforest diversity in changing circumstances.

PMID- 24312494
TI  - An effective model for screening obstructive sleep apnea: a large-scale
      diagnostic study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) causes high morbidity and mortality and
      is independently associated with an increased likelihood of multiple
      complications. The diagnosis of OSA is presently time-consuming, labor-intensive
      and inaccessible. AIM: This study sought to develop a simple and efficient model
      for identifying OSA in Chinese adult population. METHODS: In this study, the
      efficiency of Epworth Sleepiness Scale (ESS) and a new established prediction
      model for screening OSA were evaluated in the test cohort (2,032 participants)
      and confirmed in an independent validation cohort (784 participants). RESULTS: In
      the test cohort, a high specificity (82.77%, 95% confidence interval [CI], 77.36
      87.35) and a moderate sensitivity (61.65%, 95% CI, 59.35-63.91) were obtained at
      the threshold of nine for the ESS alone. Notably, sex-stratified analysis
      revealed different optimum cut-off points: nine for males and six for females.
      The new generated screening model, including age, waist circumference, ESS score,
      and minimum oxygen saturation (SaO2) as independent variables, revealed a higher
      sensitivity (89.13%, 95% CI, 87.60-90.53) and specificity (90.34%, 95% CI, 85.85
      93.77) at the best cut-off point. Through receiver operating characteristics
      curve analysis, the area under the receiver operating characteristics curve of
      the model was found significantly larger than that of the ESS alone (0.955 vs.
      0.774, P<0.0001). All these results were confirmed in the validation cohort.
      CONCLUSIONS: A practical screening model comprising minimum SaO2 and other
      parameters could efficiently identify undiagnosed OSA from the high-risk
      patients. Additionally, a sex-specific difference should be considered if the ESS
      alone is used.

PMID- 24312495
TI  - miR-150 promotes human breast cancer growth and malignant behavior by targeting
      the pro-apoptotic purinergic P2X7 receptor.
AB  - The P2X7 receptor regulates cell growth through mediation of apoptosis. Low level
      expression of P2X7 has been linked to cancer development because tumor cells
      harboring a defective P2X7 mechanism can escape P2X7 pro-apoptotic control.
      microRNAs (miRNAs) function as negative regulators of post-transcriptional gene
      expression, playing major roles in cellular differentiation, proliferation, and
      metastasis. In this study, we found that miR-150 was over-expressed in breast
      cancer cell lines and tissues. In these breast cancer cell lines, blocking the
      action of miR-150 with inhibitors leads to cell death, while ectopic expression
      of the miR-150 results in increased cell proliferation. We deploy a microRNA
      sponge strategy to inhibit miR-150 in vitro, and the result demonstrates that the
      3'-untranslated region (3'UTR) of P2X7 receptor contains a highly conserved miR
      150-binding motif and its direct interaction with miR-150 down-regulates
      endogenous P2X7 protein levels. Furthermore, our findings demonstrate that miR
      150 over-expression promotes growth, clonogenicity and reduces apoptosis in
      breast cancer cells. Meanwhile, these findings can be decapitated in nude mice
      with breast cancer xenografts. Finally, these observations strengthen our working
      hypothesis that up-regulation of miR-150 in breast cancer is inversely associated
      with P2X7 receptor expression level. Together, these findings establish miR-150
      as a novel regulator of P2X7 and a potential therapeutic target for breast
      cancer. 

PMID- 24312496
TI  - Active inhibitor-1 maintains protein hyper-phosphorylation in aging hearts and
      halts remodeling in failing hearts.
AB  - Impaired sarcoplasmic reticulum calcium cycling and depressed contractility are
      key characteristics in heart failure. Defects in sarcoplasmic reticulum function
      are characterized by decreased SERCA2a Ca-transport that is partially
      attributable to dephosphorylation of its regulator phospholamban by increased
      protein phosphatase 1 activity. Inhibition of protein phosphatase 1 through
      activation of its endogenous inhibitor-1 has been shown to enhance cardiac Ca
      handling and contractility as well as protect from pathological stress remodeling
      in young mice. In this study, we assessed the long-term effects of inducible
      expression of constitutively active inhibitor-1 in the adult heart and followed
      function and remodeling through the aging process, up to 20 months. Mice with
      inhibitor-1 had normal survival and similar function to WTs. There was no overt
      remodeling as evidenced by measures of left ventricular end-systolic and
      diastolic diameters and posterior wall dimensions, heart weight to tibia length
      ratio, and histology. Higher phosphorylation of phospholamban at both Ser16 and
      Thr17 was maintained in aged hearts with active inhibitor-1, potentially
      offsetting the effects of elevated Ser2815-phosphorylation in ryanodine receptor,
      as there were no increases in arrhythmias under stress conditions in 20-month old
      mice. Furthermore, long-term expression of active inhibitor-1 via recombinant
      adeno-associated virus type 9 gene transfer in rats with pressure-overload
      induced heart failure improved function and prevented remodeling, associated with
      increased phosphorylation of phospholamban at Ser16 and Thr17. Thus, chronic
      inhibition of protein phosphatase 1, through increases in active inhibitor-1,
      does not accelerate age-related cardiomyopathy and gene transfer of this molecule
      in vivo improves function and halts remodeling in the long term. 

PMID- 24312497
TI  - Influence of precision of emission characteristic parameters on model prediction
      error of VOCs/formaldehyde from dry building material.
AB  - Mass transfer models are useful in predicting the emissions of volatile organic
      compounds (VOCs) and formaldehyde from building materials in indoor environments.
      They are also useful for human exposure evaluation and in sustainable building
      design. The measurement errors in the emission characteristic parameters in these
      mass transfer models, i.e., the initial emittable concentration (C 0), the
      diffusion coefficient (D), and the partition coefficient (K), can result in
      errors in predicting indoor VOC and formaldehyde concentrations. These errors
      have not yet been quantitatively well analyzed in the literature. This paper
      addresses this by using modelling to assess these errors for some typical
      building conditions. The error in C 0, as measured in environmental chambers and
      applied to a reference living room in Beijing, has the largest influence on the
      model prediction error in indoor VOC and formaldehyde concentration, while the
      error in K has the least effect. A correlation between the errors in D, K, and C
      0 and the error in the indoor VOC and formaldehyde concentration prediction is
      then derived for engineering applications. In addition, the influence of
      temperature on the model prediction of emissions is investigated. It shows the
      impact of temperature fluctuations on the prediction errors in indoor VOC and
      formaldehyde concentrations to be less than 7% at 23+/-0.5 degrees C and less
      than 30% at 23+/-2 degrees C. 

PMID- 24312499
TI  - PaGenBase: a pattern gene database for the global and dynamic understanding of
      gene function.
AB  - Pattern genes are a group of genes that have a modularized expression behavior
      under serial physiological conditions. The identification of pattern genes will
      provide a path toward a global and dynamic understanding of gene functions and
      their roles in particular biological processes or events, such as development and
      pathogenesis. In this study, we present PaGenBase, a novel repository for the
      collection of tissue- and time-specific pattern genes, including specific genes,
      selective genes, housekeeping genes and repressed genes. The PaGenBase database
      is now freely accessible at http://bioinf.xmu.edu.cn/PaGenBase/. In the current
      version (PaGenBase 1.0), the database contains 906,599 pattern genes derived from
      the literature or from data mining of more than 1,145,277 gene expression
      profiles in 1,062 distinct samples collected from 11 model organisms. Four
      statistical parameters were used to quantitatively evaluate the pattern genes.
      Moreover, three methods (quick search, advanced search and browse) were designed
      for rapid and customized data retrieval. The potential applications of PaGenBase
      are also briefly described. In summary, PaGenBase will serve as a resource for
      the global and dynamic understanding of gene function and will facilitate high
      level investigations in a variety of fields, including the study of development,
      pathogenesis and novel drug discovery. 

PMID- 24312498
TI  - PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders.
AB  - The frequent comorbidity of Autism Spectrum Disorders (ASDs) with epilepsy
      suggests a shared underlying genetic susceptibility; several genes, when mutated,
      can contribute to both disorders. Recently, PRICKLE1 missense mutations were
      found to segregate with ASD. However, the mechanism by which mutations in this
      gene might contribute to ASD is unknown. To elucidate the role of PRICKLE1 in
      ASDs, we carried out studies in Prickle1(+/-) mice and Drosophila, yeast, and
      neuronal cell lines. We show that mice with Prickle1 mutations exhibit ASD-like
      behaviors. To find proteins that interact with PRICKLE1 in the central nervous
      system, we performed a yeast two-hybrid screen with a human brain cDNA library
      and isolated a peptide with homology to SYNAPSIN I (SYN1), a protein involved in
      synaptogenesis, synaptic vesicle formation, and regulation of neurotransmitter
      release. Endogenous Prickle1 and Syn1 co-localize in neurons and physically
      interact via the SYN1 region mutated in ASD and epilepsy. Finally, a mutation in
      PRICKLE1 disrupts its ability to increase the size of dense-core vesicles in PC12
      cells. Taken together, these findings suggest PRICKLE1 mutations contribute to
      ASD by disrupting the interaction with SYN1 and regulation of synaptic vesicles. 

PMID- 24312500
TI  - The impact of structural and functional parameters in glaucoma patients on
      patient-reported visual functioning.
AB  - BACKGROUND: To evaluate the impact of structural changes of the retinal nerve
      fiber layer (RNFL), and visual field loss, on functional impairment assessed by
      patient-reported visual functioning in glaucoma. METHODS: Patients with
      glaucomatous optic nerve damage were enrolled in this cross-sectional study.
      Peripapillary RNFL thickness was obtained with spectral-domain optical coherence
      tomography (SD-OCT). Function was assessed by patient-reported visual functioning
      using the Rasch-calibrated Glaucoma Activity Limitation 9 (GAL-9) questionnaire
      and standard automated perimetry. The impact of peripapillary RNFL loss on
      functional impairment was analyzed with correlation and linear regression
      analyses. RESULTS: A total of 176 eyes from 88 glaucoma patients were included.
      The SD-OCT assessed temporal-superior and temporal-inferior RNFL sector of the
      worse eye revealed significant correlation with the GAL-9 scores (r=-0.298,
      p=0.011 and r=-0.251, p=0.033, respectively). In mutivariate regression analysis,
      the best predictors for patient-reported visual functioning were visual acuity of
      the better eye and mean defect of the worse eye (R(2)=0.334), while structural
      parameters could not enhance the prediction of GAL-9 scores. CONCLUSIONS: Self
      reported visual functioning of patients with glaucoma is better predicted by
      visual performance data than structural parameters. However, some structural
      changes of the worse eye are significantly correlated with patient-reported
      visual functioning.

PMID- 24312502
TI  - Dark energy from discrete spacetime.
AB  - Dark energy accounts for most of the matter-energy content of our universe, yet
      current theories of its origin rely on radical physical assumptions such as the
      holographic principle or controversial anthropic arguments. We give a better
      motivated explanation for dark energy, claiming that it arises from a small
      negative scalar-curvature present even in empty spacetime. The vacuum has this
      curvature because spacetime is fundamentally discrete and there are more ways for
      a discrete geometry to have negative curvature than positive. We explicitly
      compute this effect using a variant of the well known dynamical-triangulations
      (DT) model for quantum gravity. Our model predicts a time-varying non-zero
      cosmological constant with a current value, [Formula: see text] in natural units,
      in agreement with observation. This calculation is made possible by a novel
      characterization of the possible DT action values combined with numerical
      evidence concerning their degeneracies. 

PMID- 24312501
TI  - Proteomic analysis reveals differentially regulated protein acetylation in human
      amyotrophic lateral sclerosis spinal cord.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative
      disease that primarily affects motor neurons in the brain and spinal cord.
      Histone deacetylase (HDAC) inhibitors have neuroprotective effects potentially
      useful for the treatment of neurodegenerative diseases including ALS; however,
      the molecular mechanisms underlying their potential efficacy is not well
      understood. Here we report that protein acetylation in urea-soluble proteins is
      differently regulated in post-mortem ALS spinal cord. Two-dimensional
      electrophoresis (2-DE) analysis reveals several protein clusters with similar
      molecular weight but different charge status. Liquid chromatography and tandem
      mass spectrometry (LC-MS/MS) identifies glial fibrillary acidic protein (GFAP) as
      the dominant component in the protein clusters. Further analysis indicates six
      heavily acetylated lysine residues at positions 89, 153, 189, 218, 259 and 331 of
      GFAP. Immunoprecipitation followed by Western blotting confirms that the larger
      form of GFAP fragments are acetylated and upregulated in ALS spinal cord. Further
      studies demonstrate that acetylation of the proteins additional to GFAP is
      differently regulated, suggesting that acetylation and/or deacetylation play an
      important role in pathogenesis of ALS. 

PMID- 24312503
TI  - Co-transplantation of GDNF-overexpressing neural stem cells and fetal
      dopaminergic neurons mitigates motor symptoms in a rat model of Parkinson's
      disease.
AB  - Striatal transplantation of dopaminergic (DA) neurons or neural stem cells (NSCs)
      has been reported to improve the symptoms of Parkinson's disease (PD), but the
      low rate of cell survival, differentiation, and integration in the host brain
      limits the therapeutic efficacy. We investigated the therapeutic effects of
      intracranial co-transplantation of mesencephalic NSCs stably overexpressing human
      glial-derived neurotrophic factor (GDNF-mNSCs) together with fetal DA neurons in
      the 6-OHDA rat model of PD. Striatal injection of mNSCs labeled by the contrast
      enhancer superparamagnetic iron oxide (SPIO) resulted in a hypointense signal in
      the striatum on T2-weighted magnetic resonance images that lasted for at least 8
      weeks post-injection, confirming the long-term survival of injected stem cells in
      vivo. Co-transplantation of GDNF-mNSCs with fetal DA neurons significantly
      reduced apomorphine-induced rotation, a behavioral endophenotype of PD, compared
      to sham-treated controls, rats injected with mNSCs expressing empty vector
      (control mNSCs) plus fetal DA neurons, or rats injected separately with either
      control mNSCs, GDNF-mNSCs, or fetal DA neurons. In addition, survival and
      differentiation of mNSCs into DA neurons was significantly greater following co
      transplantation of GDNF-mNSCs plus fetal DA neurons compared to the other
      treatment groups as indicated by the greater number of cell expressing both the
      mNSCs lineage tracer enhanced green fluorescent protein (eGFP) and the DA neuron
      marker tyrosine hydroxylase. The success of cell-based therapies for PD may be
      greatly improved by co-transplantation of fetal DA neurons with mNSCs genetically
      modified to overexpress trophic factors such as GDNF that support differentiation
      into DA cells and their survival in vivo. 

PMID- 24312504
TI  - NikA/TcsC histidine kinase is involved in conidiation, hyphal morphology, and
      responses to osmotic stress and antifungal chemicals in Aspergillus fumigatus.
AB  - The fungal high osmolarity glycerol (HOG) pathway is composed of a two-component
      system (TCS) and Hog1-type mitogen-activated protein kinase (MAPK) cascade. A
      group III (Nik1-type) histidine kinase plays a major role in the HOG pathway of
      several filamentous fungi. In this study, we characterized a group III histidine
      kinase, NikA/TcsC, in the life-threatening pathogenic fungus, Aspergillus
      fumigatus. A deletion mutant of nikA showed low conidia production, abnormal
      hyphae, marked sensitivity to high osmolarity stresses, and resistance to cell
      wall perturbing reagents such as congo red and calcofluor white, as well as to
      fungicides such as fludioxonil, iprodione, and pyrrolnitrin. None of these
      phenotypes were observed in mutants of the SskA response regulator and SakA MAPK,
      which were thought to be downstream components of NikA. In contrast, in response
      to fludioxonil treatment, NikA was implicated in the phosphorylation of SakA MAPK
      and the transcriptional upregulation of catA, dprA, and dprB, which are regulated
      under the control of SakA. We then tested the idea that not only NikA, but also
      the other 13 histidine kinases play certain roles in the regulation of the HOG
      pathway. Interestingly, the expression of fos1, phkA, phkB, fhk5, and fhk6
      increased by osmotic shock or fludioxonil treatment in a SakA-dependent manner.
      However, deletion mutants of the histidine kinases showed no significant defects
      in growth under the tested conditions. Collectively, although the signal
      transduction network related to NikA seems complicated, NikA plays a crucial role
      in several aspects of A. fumigatus physiology and, to a certain extent, modulates
      the HOG pathway. 

PMID- 24312505
TI  - Phylodynamic profile of HIV-1 subtype B, CRF01_AE and the recently emerging
      CRF51_01B among men who have sex with men (MSM) in Singapore.
AB  - HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who
      have sex with men (MSM) in Singapore. The genetic history, population dynamics
      and pattern of transmission networks of these genotypes remain largely unknown.
      We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the
      recently characterized CRF51_01B strains circulating among the MSM population in
      Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naive MSM were
      recruited between February 2008 and August 2009. Phylogenetic reconstructions of
      the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2:
      7803 - 8276) of the env gene uncovered five monophyletic transmission networks
      (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of
      different sizes (involving 3 - 23 MSM subjects, supported by posterior
      probability measure of 1.0). Bayesian coalescent analysis estimated that the
      emergence and dissemination of multiple sub-epidemic networks occurred between
      1995 and 2005, driven largely by subtype B and later followed by CRF01_AE.
      Exponential increase in effective population size for both subtype B and CRF01_AE
      occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical
      estimates suggested that the novel CRF51_01B lineages were probably generated
      through series of recombination events involving CRF01_AE and multiple subtype B
      ancestors. Our study provides the first insight on the phylodynamic profiles of
      HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in
      Singapore. 

PMID- 24312507
TI  - Detecting inter-cusp and inter-tooth wear patterns in rhinocerotids.
AB  - Extant rhinos are the largest extant herbivores exhibiting dietary
      specialisations for both browse and grass. However, the adaptive value of the
      wear-induced tooth morphology in rhinos has not been widely studied, and data on
      individual cusp and tooth positions have rarely been published. We evaluated
      upper cheek dentition of browsing Diceros bicornis and Rhinoceros sondaicus,
      mixed-feeding R. unicornis and grazing Ceratotherium simum using an extended
      mesowear method adapted for rhinos. We included single cusp scoring (EM(R)-S) to
      investigate inter-cusp and inter-tooth wear patterns. In accordance with previous
      reports, general mesowear patterns in D. bicornis and R. sondaicus were attrition
      dominated and C. simum abrasion-dominated, reflecting their respective diets.
      Mesowear patterns for R. unicornis were more attrition-dominated than anticipated
      by the grass-dominated diet, which may indicate a low intake of environmental
      abrasives. EM(R)-S increased differentiation power compared to classical
      mesowear, with significant inter-cusp and inter-tooth differences detected. In D.
      bicornis, the anterior cusp was consistently more abrasion-dominated than the
      posterior. Wear differences in cusp position may relate to morphological
      adaptations to dietary regimes. Heterogeneous occlusal surfaces may facilitate
      the comminution of heterogeneous browse, whereas uniform, broad grinding surfaces
      may enhance the comminution of physically more homogeneous grass. A negative
      tooth wear gradient was found in D. bicornis, R. sondaicus and R. unicornis, with
      wear patterns becoming less abrasion-dominated from premolars to molars. No such
      gradients were evident in C. simum which displayed a uniform wear pattern. In
      browsers, premolars may be exposed to higher relative grit loads, which may
      result in the development of wear gradients. The second premolar may also have a
      role in food cropping. In grazers, high absolute amounts of ingested abrasives
      may override other signals, leading to a uniform wear pattern and dental function
      along the tooth row, which could relate to the observed evolution towards
      homodonty. 

PMID- 24312506
TI  - Computational multiscale toxicodynamic modeling of silver and carbon nanoparticle
      effects on mouse lung function.
AB  - A computational, multiscale toxicodynamic model has been developed to quantify
      and predict pulmonary effects due to uptake of engineered nanomaterials (ENMs) in
      mice. The model consists of a collection of coupled toxicodynamic modules, that
      were independently developed and tested using information obtained from the
      literature. The modules were developed to describe the dynamics of tissue with
      explicit focus on the cells and the surfactant chemicals that regulate the
      process of breathing, as well as the response of the pulmonary system to
      xenobiotics. Alveolar type I and type II cells, and alveolar macrophages were
      included in the model, along with surfactant phospholipids and surfactant
      proteins, to account for processes occurring at multiple biological scales,
      coupling cellular and surfactant dynamics affected by nanoparticle exposure, and
      linking the effects to tissue-level lung function changes. Nanoparticle
      properties such as size, surface chemistry, and zeta potential were explicitly
      considered in modeling the interactions of these particles with biological media.
      The model predictions were compared with in vivo lung function response
      measurements in mice and analysis of mice lung lavage fluid following exposures
      to silver and carbon nanoparticles. The predictions were found to follow the
      trends of observed changes in mouse surfactant composition over 7 days post
      dosing, and are in good agreement with the observed changes in mouse lung
      function over the same period of time. 

PMID- 24312508
TI  - Sensitivity of soil respiration to variability in soil moisture and temperature
      in a humid tropical forest.
AB  - Precipitation and temperature are important drivers of soil respiration. The role
      of moisture and temperature are generally explored at seasonal or inter-annual
      timescales; however, significant variability also occurs on hourly to daily time
      scales. We used small (1.54 m(2)), throughfall exclusion shelters to evaluate the
      role soil moisture and temperature as temporal controls on soil CO2 efflux from a
      humid tropical forest in Puerto Rico. We measured hourly soil CO2 efflux,
      temperature and moisture in control and exclusion plots (n = 6) for 6-months. The
      variance of each time series was analyzed using orthonormal wavelet
      transformation and Haar-wavelet coherence. We found strong negative coherence
      between soil moisture and soil respiration in control plots corresponding to a
      two-day periodicity. Across all plots, there was a significant parabolic
      relationship between soil moisture and soil CO2 efflux with peak soil respiration
      occurring at volumetric soil moisture of approximately 0.375 m(3)/m(3). We
      additionally found a weak positive coherence between CO2 and temperature at
      longer time-scales and a significant positive relationship between soil
      temperature and CO2 efflux when the analysis was limited to the control plots.
      The coherence between CO2 and both temperature and soil moisture were reduced in
      exclusion plots. The reduced CO2 response to temperature in exclusion plots
      suggests that the positive effect of temperature on CO2 is constrained by soil
      moisture availability. 

PMID- 24312509
TI  - Social influences on inequity aversion in children.
AB  - Adults and children are willing to sacrifice personal gain to avoid both
      disadvantageous and advantageous inequity. These two forms of inequity aversion
      follow different developmental trajectories, with disadvantageous inequity
      aversion emerging around 4 years and advantageous inequity aversion emerging
      around 8 years. Although inequity aversion is assumed to be specific to
      situations where resources are distributed among individuals, the role of social
      context has not been tested in children. Here, we investigated the influence of
      two aspects of social context on inequity aversion in 4- to 9-year-old children:
      (1) the role of the experimenter distributing rewards and (2) the presence of a
      peer with whom rewards could be shared. Experiment 1 showed that children
      rejected inequity at the same rate, regardless of whether the experimenter had
      control over reward allocations. This indicates that children's decisions are
      based upon reward allocations between themselves and a peer and are not attempts
      to elicit more favorable distributions from the experimenter. Experiment 2
      compared rejections of unequal reward allocations in children interacting with or
      without a peer partner. When faced with a disadvantageous distribution, children
      frequently rejected a smaller reward when a larger reward was visible, even if no
      partner would obtain the larger reward. This suggests that nonsocial factors
      partly explain disadvantageous inequity rejections. However, rejections of
      disadvantageous distributions were higher when the larger amount would go to a
      peer, indicating that social context enhances disadvantageous inequity aversion.
      By contrast, children rejected advantageous distributions almost exclusively in
      the social context. Therefore, advantageous inequity aversion appears to be
      genuinely social, highlighting its potential relevance for the development of
      fairness concerns. By comparing social and nonsocial factors, this study provides
      a detailed picture of the expression of inequity aversion in human ontogeny and
      raises questions about the function and evolution of inequity aversion in humans.

PMID- 24312510
TI  - Chronic clomipramine treatment reverses core symptom of depression in subordinate
      tree shrews.
AB  - Chronic stress is the major cause of clinical depression. The behavioral signs of
      depression, including anhedonia, learning and memory deficits, and sleep
      disruption, result from the damaging effects of stress hormones on specific
      neural pathways. The Chinese tree shrew (Tupaia belangeri chinensis) is an
      aggressive non-human primate with a hierarchical social structure that has become
      a well-established model of the behavioral, endocrine, and neurobiological
      changes associated with stress-induced depression. The tricyclic antidepressant
      clomipramine treats many of the core symptoms of depression in humans. To further
      test the validity of the tree shrew model of depression, we examined the effects
      of clomipramine on depression-like behaviors and physiological stress responses
      induced by social defeat in subordinate tree shrews. Social defeat led to weight
      loss, anhedonia (as measured by sucrose preference), unstable fluctuations in
      locomotor activity, sustained urinary cortisol elevation, irregular cortisol
      rhythms, and deficient hippocampal long-term potentiation (LTP). Clomipramine
      ameliorated anhedonia and irregular locomotor activity, and partially rescued the
      irregular cortisol rhythm. In contrast, weight loss increased, cortisol levels
      were even higher, and in vitro LTP was still impaired in the clomipramine
      treatment group. These results demonstrate the unique advantage of the tree shrew
      social defeat model of depression. 

PMID- 24312511
TI  - Changes in the potential multiple cropping system in response to climate change
      in China from 1960-2010.
AB  - The multiple cropping practice is essential to agriculture because it has been
      shown to significantly increase the grain yield and promote agricultural economic
      development. In this study, potential multiple cropping systems in China are
      calculated based on meteorological observation data by using the Agricultural
      Ecology Zone (AEZ) model. Following this, the changes in the potential cropping
      systems in response to climate change between the 1960s and the 2010s were
      subsequently analyzed. The results indicate that the changes of potential
      multiple cropping systems show tremendous heterogeneity in respect to the spatial
      pattern in China. A key finding is that the magnitude of change of the potential
      cropping systems showed a pattern of increase both from northern China to
      southern China and from western China to eastern China. Furthermore, the area
      found to be suitable only for single cropping decreased, while the area suitable
      for triple cropping increased significantly from the 1960s to the 2000s. During
      the studied period, the potential multiple cropping index (PMCI) gap between rain
      fed and irrigated scenarios increased from 18% to 24%, which indicated noticeable
      growth of water supply limitations under the rain-fed scenario. The most
      significant finding of this research was that from the 1960s to the 2000s climate
      change had led to a significant increase of PMCI by 13% under irrigated scenario
      and 7% under rain-fed scenario across the whole of China. Furthermore, the growth
      of the annual mean temperature is identified as the main reason underlying the
      increase of PMCI. It has also been noticed that across China the changes of
      potential multiple cropping systems under climate change were different from
      region to region. 

PMID- 24312513
TI  - Multiplex cytological profiling assay to measure diverse cellular states.
AB  - Computational methods for image-based profiling are under active development, but
      their success hinges on assays that can capture a wide range of phenotypes. We
      have developed a multiplex cytological profiling assay that "paints the cell"
      with as many fluorescent markers as possible without compromising our ability to
      extract rich, quantitative profiles in high throughput. The assay detects seven
      major cellular components. In a pilot screen of bioactive compounds, the assay
      detected a range of cellular phenotypes and it clustered compounds with similar
      annotated protein targets or chemical structure based on cytological profiles.
      The results demonstrate that the assay captures subtle patterns in the
      combination of morphological labels, thereby detecting the effects of chemical
      compounds even though their targets are not stained directly. This image-based
      assay provides an unbiased approach to characterize compound- and disease
      associated cell states to support future probe discovery.

PMID- 24312512
TI  - Inhibitory effect of baicalin on iNOS and NO expression in intestinal mucosa of
      rats with acute endotoxemia.
AB  - The mechanism by which baicalin modulated the expression of inducible nitric
      oxide synthase (iNOS) and nitric oxide (NO) in the mucosa of distal ileum was
      investigated in a rat model of acute endo-toxemia induced by intraperitoneal
      injection of bacterial lipopolysaccharide (LPS). The experiment demonstrated that
      LPS upregulated iNOS mRNA and protein expression as well as NO produc-tion
      (measured as the stable degradation production, nitrites). LPS not only increased
      toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor gamma
      (PPARgamma) content, but also activated p38 and activating transcription factor 2
      (ATF2) and inactivated PPARgamma via phosphorylation. Inhibition of p38
      signalling pathway by chemical inhibitor SB202190 and small interfering RNA
      (siRNA) ameliorated LPS-induced iNOS generation, while suppression of PPARgamma
      pathway by SR-202 boosted LPS-elicited iNOS expression. Baicalin treatment (I)
      attenuated LPS-induced iNOS mRNA and protein as well as nitrites generation, and
      (II) ameliorated LPS-elicited TLR4 and PPARgamma production, and (III) inhibited
      p38/ATF2 phosphorylation leading to suppression of p38 signalling, and (IV)
      prevented PPARgamma from phosphorylation contributing to maintainence of
      PPARgamma bioactivity. However, SR-202 co-treatment (I) partially abrogated the
      inhibitory effect of baicalin on iNOS mRNA expression, and (II) partially
      reversed baicalin-inhibited p38 phosphorylation. In summary, baicalin could
      ameliorate LPS-induced iNOS and NO overproduction in mucosa of rat terminal ileum
      via inhibition of p38 signalling cascade and activation of PPARgamma pathway.
      There existed a interplay between the two signalling pathways. 

PMID- 24312514
TI  - Disparity expression of Notch1 in benign and malignant colorectal diseases.
AB  - BACKGROUND AND OBJECTIVES: Although there was growing evidence supporting the
      hypothesis that Notch1 was one of the few candidate genes linked with colorectal
      cancer (CRC) susceptibility, the precise level of Notch1 protein expression in
      benign and malignant colorectal diseases was still unknown. Our study has
      investigated the Notch1 expression in benign and malignant colorectal diseases as
      well as to investigate the role and clinicopathological significance of aberrant
      expression of Notch1 in CRC. METHODS: The protein expression of Notch1 was
      examined by immunohistochemistry in 901 clinical specimens with colorectal
      diseases, including 220 patients with ulcerative colitis, 232 patients with
      colorectal adenoma and 449 patients with colorectal cancer. Associations between
      the expression of Notch1 and various clinicopathological features, as well as
      survival status, were studied. RESULTS: Cytoplasmic Notch1 was expressed in 7.7%
      of patients with ulcerative colitis, 14.7% of patients with colorectal adenoma
      and 58.0% of patients with colorectal cancer, respectively. Colorectal cancer
      patients with high expression levels of Notch1 showed lower overall survival (OS)
      and disease-free survival (DFS) rates than those patients with low Notch1
      expression. CONCLUSIONS: Expression level of Notch1 was gradually increased from
      precancerous lesions to cancer. It might play as an oncogene in the CRC
      development, and might be potentially used as a biomarker for prognosis of CRCs.

PMID- 24312515
TI  - Transorbital sonographic evaluation of normal optic nerve sheath diameter in
      healthy volunteers in Bangladesh.
AB  - INTRODUCTION: Measurement of optic nerve sheath diameter (ONSD) by ultrasound is
      increasingly used as a marker to detect raised intracranial pressure (ICP). ONSD
      varies with age and there is no clear consensus between studies for an upper
      limit of normal. Knowledge of normal ONSD in a healthy population is essential to
      interpret this measurement. METHODS: In a prospective observational study, ONSD
      was measured using a 15 MHz ultrasound probe in healthy volunteers in Chittagong,
      Bangladesh. The aims were to determine the normal range of ONSD in healthy
      Bangladeshi adults and children, compare measurements in males and females,
      horizontal and vertical beam orientations and left and right eyes in the same
      individual and to determine whether ONSD varies with head circumference
      independent of age. RESULTS: 136 subjects were enrolled, 12.5% of whom were age
      16 or under. Median ONSD was 4.41 mm with 95% of subjects in the range 4.25-4.75
      mm. ONSD was bimodally distributed. There was no relationship between ONSD and
      age (>=4 years), gender, head circumference, and no difference in left vs right
      eye or horizontal vs vertical beam. CONCLUSIONS: Ultrasonographic ONSD in
      Bangladeshi healthy volunteers has a narrow bimodal distribution independent of
      age (>=4 years), gender and head circumference. ONSD >4.75 mm in this population
      should be considered abnormal.

PMID- 24312517
TI  - Effect of formant frequency spacing on perceived gender in pre-pubertal
      children's voices.
AB  - BACKGROUND: It is usually possible to identify the sex of a pre-pubertal child
      from their voice, despite the absence of sex differences in fundamental frequency
      at these ages. While it has been suggested that the overall spacing between
      formants (formant frequency spacing--DeltaF) is a key component of the expression
      and perception of sex in children's voices, the effect of its continuous
      variation on sex and gender attribution has not yet been investigated.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study we manipulated voice DeltaF
      of eight year olds (two boys and two girls) along continua covering the observed
      variation of this parameter in pre-pubertal voices, and assessed the effect of
      this variation on adult ratings of speakers' sex and gender in two separate
      experiments. In the first experiment (sex identification) adults were asked to
      categorise the voice as either male or female. The resulting identification
      function exhibited a gradual slope from male to female voice categories. In the
      second experiment (gender rating), adults rated the voices on a continuum from
      "masculine boy" to "feminine girl", gradually decreasing their masculinity
      ratings as DeltaF increased. CONCLUSIONS/SIGNIFICANCE: These results indicate
      that the role of DeltaF in voice gender perception, which has been reported in
      adult voices, extends to pre-pubertal children's voices: variation in DeltaF not
      only affects the perceived sex, but also the perceived masculinity or femininity
      of the speaker. We discuss the implications of these observations for the
      expression and perception of gender in children's voices given the absence of
      anatomical dimorphism in overall vocal tract length before puberty.

PMID- 24312516
TI  - Is there an association between work stress and diurnal cortisol patterns?
      Findings from the Whitehall II study.
AB  - OBJECTIVE: The evidence on whether there is work stress related dysregulation of
      the hypothalamic-pituitary-adrenal axis is equivocal. This study assessed the
      relation between work stress and diurnal cortisol rhythm in a large-scale
      occupational cohort, the Whitehall II study. METHODS: Work stress was assessed in
      two ways, using the job-demand-control (JDC) and the effort-reward-imbalance
      (ERI) models. Salivary cortisol samples were collected six times over a normal
      day in 2002-2004. The cortisol awakening response (CAR) and diurnal cortisol
      decline (slope) were calculated. RESULTS: In this large occupational cohort (N =
      2,126, mean age 57.1), modest differences in cortisol patterns were found for ERI
      models only, showing lower reward (beta = -0.001, P-value = 0.04) and higher ERI
      (beta = 0.002, P-value = 0.05) were related to a flatter slope in cortisol across
      the day. Meanwhile, moderate gender interactions were observed regarding CAR and
      JDC model. CONCLUSIONS: We conclude that the associations of work stress with
      cortisol are modest, with associations apparent for ERI model rather than JDC
      model.

PMID- 24312518
TI  - The rate-size trade-off structures intraspecific variation in Daphnia ambigua
      life history parameters.
AB  - The identification of trade-offs is necessary for understanding the evolution and
      maintenance of diversity. Here we employ the supply-demand (SD) body size
      optimization model to predict a trade-off between asymptotic body size and growth
      rate. We use the SD model to quantitatively predict the slope of the relationship
      between asymptotic body size and growth rate under high and low food regimes and
      then test the predictions against observations for Daphnia ambigua. Close
      quantitative agreement between observed and predicted slopes at both food levels
      lends support to the model and confirms that a 'rate-size' trade-off structures
      life history variation in this population. In contrast to classic life history
      expectations, growth and reproduction were positively correlated after
      controlling for the rate-size trade-off. We included 12 Daphnia clones in our
      study, but clone identity explained only some of the variation in life history
      traits. We also tested the hypothesis that growth rate would be positively
      related to intergenic spacer length (i.e. the growth rate hypothesis) across
      clones, but we found that clones with intermediate intergenic spacer lengths had
      larger asymptotic sizes and slower growth rates. Our results strongly support a
      resource-based optimization of body size following the SD model. Furthermore,
      because some resource allocation decisions necessarily precede others,
      understanding interdependent life history traits may require a more nested
      approach. 

PMID- 24312519
TI  - Apparent survival rates of forest birds in eastern Ecuador revisited: improvement
      in precision but no change in estimates.
AB  - Knowledge of survival rates of Neotropical landbirds remains limited, with
      estimates of apparent survival available from relatively few sites and species.
      Previously, capture-mark-recapture models were used to estimate apparent survival
      of 31 species (30 passerines, 1 Trochilidae) from eastern Ecuador based on data
      collected from 2001 to 2006. Here, estimates are updated with data from 2001-2012
      to determine how additional years of data affect estimates; estimates for six
      additional species are provided. Models assuming constant survival had highest
      support for 19 of 31 species when based on 12 years of data compared to 27 when
      based on six; models incorporating effects of transients had the highest support
      for 12 of 31 species compared to four when based on 12 and six years,
      respectively. Average apparent survival based on the most highly-supported model
      (based on model averaging, when appropriate) was 0.59 (+/- 0.02 SE) across 30
      species of passerines when based on 12 years and 0.57 (+/- 0.02) when based on
      six. Standard errors of survival estimates based on 12 years were approximately
      half those based on six years. Of 31 species in both data sets, estimates of
      apparent survival were somewhat lower for 13, somewhat higher for 17, and
      remained unchanged for one; confidence intervals for estimates based on six and
      12 years of data overlapped for all species. Results indicate that estimates of
      apparent survival are comparable but more precise when based on longer-term data
      sets; standard error of the estimates was negatively correlated with numbers of
      captures (rs  = -0.72) and recaptures (rs  = -0.93, P<0.001 in both cases). Thus,
      reasonable estimates of apparent survival may be obtained with relatively few
      years of data if sample sizes are sufficient. 

PMID- 24312520
TI  - Evidence of territoriality and species interactions from spatial point-pattern
      analyses of subarctic-nesting geese.
AB  - Quantifying spatial patterns of bird nests and nest fate provides insights into
      processes influencing a species' distribution. At Cape Churchill, Manitoba,
      Canada, recent declines in breeding Eastern Prairie Population Canada geese
      (Branta canadensis interior) has coincided with increasing populations of nesting
      lesser snow geese (Chen caerulescens caerulescens) and Ross's geese (Chen
      rossii). We conducted a spatial analysis of point patterns using Canada goose
      nest locations and nest fate, and lesser snow goose nest locations at two study
      areas in northern Manitoba with different densities and temporal durations of
      sympatric nesting Canada and lesser snow geese. Specifically, we assessed (1)
      whether Canada geese exhibited territoriality and at what scale and nest density;
      and (2) whether spatial patterns of Canada goose nest fate were associated with
      the density of nesting lesser snow geese as predicted by the protective
      association hypothesis. Between 2001 and 2007, our data suggest that Canada geese
      were territorial at the scale of nearest neighbors, but were aggregated when
      considering overall density of conspecifics at slightly broader spatial scales.
      The spatial distribution of nest fates indicated that lesser snow goose nest
      proximity and density likely influence Canada goose nest fate. Our analyses of
      spatial point patterns suggested that continued changes in the distribution and
      abundance of breeding lesser snow geese on the Hudson Bay Lowlands may have
      impacts on the reproductive performance of Canada geese, and subsequently the
      spatial distribution of Canada goose nests. 

PMID- 24312522
TI  - Knee adduction moment and medial contact force--facts about their correlation
      during gait.
AB  - The external knee adduction moment is considered a surrogate measure for the
      medial tibiofemoral contact force and is commonly used to quantify the load
      reducing effect of orthopedic interventions. However, only limited and
      controversial data exist about the correlation between adduction moment and
      medial force. The objective of this study was to examine whether the adduction
      moment is indeed a strong predictor for the medial force by determining their
      correlation during gait. Instrumented knee implants with telemetric data
      transmission were used to measure tibiofemoral contact forces in nine subjects.
      Gait analyses were performed simultaneously to the joint load measurements.
      Skeletal kinematics, as well as the ground reaction forces and inertial
      parameters, were used as inputs in an inverse dynamics approach to calculate the
      external knee adduction moment. Linear regression analysis was used to analyze
      the correlation between adduction moment and medial force for the whole stance
      phase and separately for the early and late stance phase. Whereas only moderate
      correlations between adduction moment and medial force were observed throughout
      the whole stance phase (R(2) = 0.56) and during the late stance phase (R(2) =
      0.51), a high correlation was observed at the early stance phase (R(2) = 0.76).
      Furthermore, the adduction moment was highly correlated to the medial force ratio
      throughout the whole stance phase (R(2) = 0.75). These results suggest that the
      adduction moment is a surrogate measure, well-suited to predicting the medial
      force ratio throughout the whole stance phase or medial force during the early
      stance phase. However, particularly during the late stance phase, moderate
      correlations and high inter-individual variations revealed that the predictive
      value of the adduction moment is limited. Further analyses are necessary to
      examine whether a combination of other kinematic, kinetic or neuromuscular
      factors may lead to a more reliable prediction of the force magnitude. 

PMID- 24312521
TI  - A first insight into Pycnoporus sanguineus BAFC 2126 transcriptome.
AB  - Fungi of the genus Pycnoporus are white-rot basidiomycetes widely studied because
      of their ability to synthesize high added-value compounds and enzymes of
      industrial interest. Here we report the sequencing, assembly and analysis of the
      transcriptome of Pycnoporus sanguineus BAFC 2126 grown at stationary phase, in
      media supplemented with copper sulfate. Using the 454 pyrosequencing platform we
      obtained a total of 226,336 reads (88,779,843 bases) that were filtered and de
      novo assembled to generate a reference transcriptome of 7,303 transcripts.
      Putative functions were assigned for 4,732 transcripts by searching similarities
      of six-frame translated sequences against a customized protein database and by
      the presence of conserved protein domains. Through the analysis of translated
      sequences we identified transcripts encoding 178 putative carbohydrate active
      enzymes, including representatives of 15 families with roles in lignocellulose
      degradation. Furthermore, we found many transcripts encoding enzymes related to
      lignin hydrolysis and modification, including laccases and peroxidases, as well
      as GMC oxidoreductases, copper radical oxidases and other enzymes involved in the
      generation of extracellular hydrogen peroxide and iron homeostasis. Finally, we
      identified the transcripts encoding all of the enzymes involved in terpenoid
      backbone biosynthesis pathway, various terpene synthases related to the
      biosynthesis of sesquiterpenoids and triterpenoids precursors, and also
      cytochrome P450 monooxygenases, glutathione S-transferases and epoxide hydrolases
      with potential functions in the biodegradation of xenobiotics and the
      enantioselective biosynthesis of biologically active drugs. To our knowledge this
      is the first report of a transcriptome of genus Pycnoporus and a resource for
      future molecular studies in P. sanguineus. 

PMID- 24312523
TI  - Cross-limb interference during motor learning.
AB  - It is well known that following skill learning, improvements in motor performance
      may transfer to the untrained contralateral limb. It is also well known that
      retention of a newly learned task A can be degraded when learning a competing
      task B that takes place directly after learning A. Here we investigate if this
      interference effect can also be observed in the limb contralateral to the trained
      one. Therefore, five different groups practiced a ballistic finger flexion task
      followed by an interfering visuomotor accuracy task with the same limb.
      Performance in the ballistic task was tested before the training, after the
      training and in an immediate retention test after the practice of the
      interference task for both the trained and the untrained hand. After training,
      subjects showed not only significant learning and interference effects for the
      trained limb but also for the contralateral untrained limb. Importantly, the
      interference effect in the untrained limb was dependent on the level of skill
      acquisition in the interfering motor task. These behavioural results of the
      untrained limb were accompanied by training specific changes in corticospinal
      excitability, which increased for the hemisphere ipsilateral to the trained hand
      following ballistic training and decreased during accuracy training of the
      ipsilateral hand. The results demonstrate that contralateral interference effects
      may occur, and that interference depends on the level of skill acquisition in the
      interfering motor task. This finding might be particularly relevant for
      rehabilitation. 

PMID- 24312524
TI  - Functional categorization of transcriptome in the species Symphysodon
      aequifasciatus Pellegrin 1904 (Perciformes: Cichlidae) exposed to benzo[a]pyrene
      and phenanthrene.
AB  - This study aims to evaluate the transcriptome alterations, through cDNA
      libraries, associated with the combined effects of two PAHs, benzo[a]pyrene (0.5
      ug/L) and phenanthrene (50 ug/L), present in crude oil, on specimens of
      Symphysodon aequifasciatus (discus fish) after 48 h of exposure. The cDNA
      libraries were constructed according to the SOLiDTM SAGETM protocol for
      sequencing in the SOLiD v.3 Plus sequencer. The results were analyzed by
      bioinformatics and differentially expressed genes were categorized using the gene
      ontology program. The functional categories (terms) found in the gene ontology
      and the gene network generated using STRING software were used to predict the
      adverse effects of benzo[a]pyrene and phenanthrene in the liver. In the present
      study, 27,127 genes (compared to Danio rerio database) were identified.
      Considering only those genes with a p-value less than or equal to 0.05 and
      greater than or equal to two-fold change in expression across libraries, we found
      804 genes, 438 down-regulated (54%) and 366 up-regulated (46%), in the
      experimental group compared to the control. Out of this total, 327 genes were
      successfully categorized, 174 down-regulated and 153 up-regulated, using gene
      ontology. Using String, the gene network was composed by 199 nodes, 124 of them
      resulting in 274 interactions. The results showed that even an acute exposure of
      48 h caused metabolic change in response to environmental contaminants, resulting
      in changes of cell integrity, in oxidation-reduction processes, in the immune
      response and disturbances of intracellular signaling of discus fish. Also the
      gene network has showed no central interplay cluster, exhibiting instead
      interconnected clusters interactions and connected sub-networks. These findings
      highlight that even an acute sublethal exposure of PAHs can cause metabolism
      changes that may affect survival of discus. Our findings using SOLiD coupled with
      SAGE-method resulted in a powerful and reliable means for gene expression
      analysis in discus, a non-model Amazonian fish. 

PMID- 24312525
TI  - Diet-induced over-expression of flightless-I protein and its relation to
      flightlessness in Mediterranean fruit fly, Ceratitis capitata.
AB  - The Mediterranean fruit fly (medfly), Ceratitis capitata is among the most
      economically important pests worldwide. Understanding nutritional requirement
      helps rearing healthy medfly for biocontrol of its population in fields. Flight
      ability is a high priority criterion. Two groups of medfly larvae were reared
      with two identical component diets except one with fatty acids (diet A) and
      another without it (diet B). Adults from larvae reared on diet B demonstrated
      20+/-8% of normal flight ability, whereas those from larvae reared on diet A
      displayed full flight ability of 97+/-1%. Proteomes were profiled to compare two
      groups of medfly pupae using shotgun proteomics to study dietary effects on
      flight ability. When proteins detected in pupae A were compared with those in
      pupae B, 233 and 239 proteins were, respectively, under- and over-expressed in
      pupae B, while 167 proteins were overlapped in both pupae A and B. Differential
      protein profiles indicate that nutritional deficiency induced over-expression of
      flightless-I protein (fli-I) in medfly. All proteins were subjected to Ingenuity
      Pathway Analysis (IPA) to create 13 biological networks and 17 pathways of
      interacting protein clusters in human ortholog. Fli-I, leucine-rich repeat (LRR)
      containing G protein-coupled receptor 2, LRR protein soc-2 and protein wings
      apart-like were over-expressed in pupae B. Inositol-1,4,5-trisphosphate receptor,
      protocadherin-like wing polarity protein stan and several Wnt pathway proteins
      were under-expressed in pupae B. These results suggest down-regulation of the
      Wnt/wingless signaling pathway, which consequently may result in flightlessness
      in pupae B. The fli-I gene is known to be located within the Smith-Magenis
      syndrome (SMS) region on chromosome 17, and thus, we speculate that nutritional
      deficiency might induce over-expression of fli-I (or fli-I gene) and be
      associated with human SMS. However, more evidence would be needed to confirm our
      speculation. 

PMID- 24312527
TI  - Calculation of evolutionary correlation between individual genes and full-length
      genome: a method useful for choosing phylogenetic markers for molecular
      epidemiology.
AB  - Individual genes or regions are still commonly used to estimate the phylogenetic
      relationships among viral isolates. The genomic regions that can faithfully
      provide assessments consistent with those predicted with full-length genome
      sequences would be preferable to serve as good candidates of the phylogenetic
      markers for molecular epidemiological studies of many viruses. Here we employed a
      statistical method to evaluate the evolutionary relationships between individual
      viral genes and full-length genomes without tree construction as a way to
      determine which gene can match the genome well in phylogenetic analyses. This
      method was performed by calculation of linear correlations between the genetic
      distance matrices of aligned individual gene sequences and aligned genome
      sequences. We applied this method to the phylogenetic analyses of porcine
      circovirus 2 (PCV2), measles virus (MV), hepatitis E virus (HEV) and Japanese
      encephalitis virus (JEV). Phylogenetic trees were constructed for comparisons and
      the possible factors affecting the method accuracy were also discussed in the
      calculations. The results revealed that this method could produce results
      consistent with those of previous studies about the proper consensus sequences
      that could be successfully used as phylogenetic markers. And our results also
      suggested that these evolutionary correlations could provide useful information
      for identifying genes that could be used effectively to infer the genetic
      relationships. 

PMID- 24312526
TI  - Modeling long-term host cell-Giardia lamblia interactions in an in vitro co
      culture system.
AB  - Globally, there are greater than 700,000 deaths per year associated with
      diarrheal disease. The flagellated intestinal parasite, Giardia lamblia, is one
      of the most common intestinal pathogens in both humans and animals throughout the
      world. While attached to the gastrointestinal epithelium, Giardia induces
      epithelial cell apoptosis, disrupts tight junctions, and increases intestinal
      permeability. The underlying cellular and molecular mechanisms of giardiasis,
      including the role lamina propria immune cells, such as macrophages, play in
      parasite control or clearance are poorly understood. Thus far, one of the major
      obstacles in ascertaining the mechanisms of Giardia pathology is the lack of a
      functionally relevant model for the long-term study of the parasite in vitro.
      Here we report on the development of an in vitro co-culture model which maintains
      the basolateral-apical architecture of the small intestine and allows for long
      term survival of the parasite. Using transwell inserts, Caco-2 intestinal
      epithelial cells and IC-21 macrophages are co-cultured in the presence of Giardia
      trophozoites. Using the developed model, we show that Giardia trophozoites
      survive over 21 days and proliferate in a combination media of Caco-2 cell and
      Giardia medium. Giardia induces apoptosis of epithelial cells through caspase-3
      activation and macrophages do not abrogate this response. Additionally,
      macrophages induce Caco-2 cells to secrete the pro-inflammatory cytokines, GRO
      and IL-8, a response abolished by Giardia indicating parasite induced suppression
      of the host immune response. The co-culture model provides additional complexity
      and information when compared to a single-cell model. This model will be a
      valuable tool for answering long-standing questions on host-parasite biology that
      may lead to discovery of new therapeutic interventions. 

PMID- 24312528
TI  - Tropical fishes dominate temperate reef fish communities within western Japan.
AB  - Climate change is resulting in rapid poleward shifts in the geographical
      distribution of tropical and subtropical fish species. We can expect that such
      range shifts are likely to be limited by species-specific resource requirements,
      with temperate rocky reefs potentially lacking a range of settlement substrates
      or specific dietary components important in structuring the settlement and
      success of tropical and subtropical fish species. We examined the importance of
      resource use in structuring the distribution patterns of range shifting tropical
      and subtropical fishes, comparing this with resident temperate fish species
      within western Japan (Tosa Bay); the abundance, diversity, size class, functional
      structure and latitudinal range of reef fishes utilizing both coral reef and
      adjacent rocky reef habitat were quantified over a 2 year period (2008-2010).
      This region has undergone rapid poleward expansion of reef-building corals in
      response to increasing coastal water temperatures, and forms one of the global
      hotspots for rapid coastal changes. Despite the temperate latitude surveyed (33
      degrees N, 133 degrees E) the fish assemblage was both numerically, and in terms
      of richness, dominated by tropical fishes. Such tropical faunal dominance was
      apparent within both coral, and rocky reef habitats. The size structure of the
      assemblage suggested that a relatively large number of tropical species are
      overwintering within both coral and rocky habitats, with a subset of these
      species being potentially reproductively active. The relatively high abundance
      and richness of tropical species with obligate associations with live coral
      resources (i.e., obligate corallivores) shows that this region holds the most
      well developed temperate-located tropical fish fauna globally. We argue that
      future tropicalisation of the fish fauna in western Japan, associated with
      increasing coral habitat development and reported increasing shifts in coastal
      water temperatures, may have considerable positive economic impacts to the local
      tourism industry and bring qualitative changes to both local and regional
      fisheries resources. 

PMID- 24312529
TI  - The mouse age phenome knowledgebase and disease-specific inter-species age
      mapping.
AB  - BACKGROUND: Similarities between mice and humans lead to generation of many mouse
      models of human disease. However, differences between the species often result in
      mice being unreliable as preclinical models for human disease. One difference
      that might play a role in lowering the predictivity of mice models to human
      diseases is age. Despite the important role age plays in medicine, it is too
      often considered only casually when considering mouse models. METHODS: We
      developed the mouse-Age Phenotype Knowledgebase, which holds knowledge about age
      related phenotypic patterns in mice. The knowledgebase was extensively populated
      with literature-derived data using text mining techniques. We then mapped between
      ages in humans and mice by comparing the age distribution pattern for 887
      diseases in both species. RESULTS: The knowledgebase was populated with over 9800
      instances generated by a text-mining pipeline. The quality of the data was
      manually evaluated, and was found to be of high accuracy (estimated precision
      >86%). Furthermore, grouping together diseases that share similar age patterns in
      mice resulted in clusters that mirror actual biomedical knowledge. Using these
      data, we matched age distribution patterns in mice and in humans, allowing for
      age differences by shifting either of the patterns. High correlation (r(2)>0.5)
      was found for 223 diseases. The results clearly indicate a difference in the age
      mapping between different diseases: age 30 years in human is mapped to 120 days
      in mice for Leukemia, but to 295 days for Anemia. Based on these results we
      generated a mice-to-human age map which is publicly available. CONCLUSIONS: We
      present here the development of the mouse-APK, its population with literature
      derived data and its use to map ages in mice and human for 223 diseases. These
      results present a further step made to bridging the gap between humans and mice
      in biomedical research.

PMID- 24312530
TI  - A mathematical model of the enhanced permeability and retention effect for
      liposome transport in solid tumors.
AB  - The discovery of the enhanced permeability and retention (EPR) effect has
      resulted in the development of nanomedicines, including liposome-based
      formulations of drugs, as cancer therapies. The use of liposomes has resulted in
      substantial increases in accumulation of drugs in solid tumors; yet, significant
      improvements in therapeutic efficacy have yet to be achieved. Imaging of the
      tumor accumulation of liposomes has revealed that this poor or variable
      performance is in part due to heterogeneous inter-subject and intra-tumoral
      liposome accumulation, which occurs as a result of an abnormal transport
      microenvironment. A mathematical model that relates liposome accumulation to the
      underlying transport properties in solid tumors could provide insight into inter
      and intra-tumoral variations in the EPR effect. In this paper, we present a
      theoretical framework to describe liposome transport in solid tumors. The
      mathematical model is based on biophysical transport equations that describe
      pressure driven fluid flow across blood vessels and through the tumor
      interstitium. The model was validated by direct comparison with computed
      tomography measurements of tumor accumulation of liposomes in three preclinical
      tumor models. The mathematical model was fit to liposome accumulation curves
      producing predictions of transport parameters that reflect the tumor
      microenvironment. Notably, all fits had a high coefficient of determination and
      predictions of interstitial fluid pressure agreed with previously published
      independent measurements made in the same tumor type. Furthermore, it was
      demonstrated that the model attributed inter-subject heterogeneity in liposome
      accumulation to variations in peak interstitial fluid pressure. These findings
      highlight the relationship between transvascular and interstitial flow dynamics
      and variations in the EPR effect. In conclusion, we have presented a theoretical
      framework that predicts inter-subject and intra-tumoral variations in the EPR
      effect based on fundamental properties of the tumor microenvironment and forms
      the basis for transport modeling of liposome drug delivery. 

PMID- 24312531
TI  - The genetic basis of a rare flower color polymorphism in Mimulus lewisii provides
      insight into the repeatability of evolution.
AB  - A long-standing question in evolutionary biology asks whether the genetic changes
      contributing to phenotypic evolution are predictable. Here, we identify a genetic
      change associated with segregating variation in flower color within a population
      of Mimulus lewisii. To determine whether these types of changes are predictable,
      we combined this information with data from other species to investigate whether
      the spectrum of mutations affecting flower color transitions differs based on the
      evolutionary time-scale since divergence. We used classic genetic techniques,
      along with gene expression and population genetic approaches, to identify the
      putative, loss-of-function mutation that generates rare, white flowers instead of
      the common, pink color in M. lewisii. We found that a frameshift mutation in an
      anthocyanin pathway gene is responsible for the white-flowered polymorphism found
      in this population of M. lewisii. Comparison of our results with data from other
      species reveals a broader spectrum of flower color mutations segregating within
      populations relative to those that fix between populations. These results suggest
      that the genetic basis of fixed differences in flower color may be predictable,
      but that for segregating variation is not. 

PMID- 24312532
TI  - Seasonal variations in the diet and foraging behaviour of dunlins Calidris alpina
      in a south European estuary: improved feeding conditions for northward migrants.
AB  - During the annual cycle, migratory waders may face strikingly different feeding
      conditions as they move between breeding areas and wintering grounds. Thus, it is
      of crucial importance that they rapidly adjust their behaviour and diet to
      benefit from peaks of prey abundance, in particular during migration, when they
      need to accumulate energy at a fast pace. In this study, we compared foraging
      behaviour and diet of wintering and northward migrating dunlins in the Tagus
      estuary, Portugal, by video-recording foraging birds and analysing their
      droppings. We also estimated energy intake rates and analysed variations in prey
      availability, including those that were active at the sediment surface. Wintering
      and northward migrating dunlins showed clearly different foraging behaviour and
      diet. In winter, birds predominantly adopted a tactile foraging technique
      (probing), mainly used to search for small buried bivalves, with some visual
      surface pecking to collect gastropods and crop bivalve siphons. Contrastingly, in
      spring dunlins generally used a visual foraging strategy, mostly to consume
      worms, but also bivalve siphons and shrimps. From winter to spring, we found a
      marked increase both in the biomass of invertebrate prey in the sediment and in
      the surface activity of worms and siphons. The combination of these two factors,
      together with the availability of shrimps in spring, most likely explains the
      changes in the diet and foraging behaviour of dunlins. Northward migrating birds
      took advantage from the improved feeding conditions in spring, achieving 65%
      higher energy intake rates as compared with wintering birds. Building on these
      results and on known daily activity budgets for this species, our results suggest
      that Tagus estuary provides high-quality feeding conditions for birds during
      their stopovers, enabling high fattening rates. These findings show that this
      large wetland plays a key role as a stopover site for migratory waders within the
      East Atlantic Flyway. 

PMID- 24312533
TI  - Activity in a premotor cortical nucleus of zebra finches is locally organized and
      exhibits auditory selectivity in neurons but not in glia.
AB  - Motor functions are often guided by sensory experience, most convincingly
      illustrated by complex learned behaviors. Key to sensory guidance in motor areas
      may be the structural and functional organization of sensory inputs and their
      evoked responses. We study sensory responses in large populations of neurons and
      neuron-assistive cells in the songbird motor area HVC, an auditory-vocal brain
      area involved in sensory learning and in adult song production. HVC spike
      responses to auditory stimulation display remarkable preference for the bird's
      own song (BOS) compared to other stimuli. Using two-photon calcium imaging in
      anesthetized zebra finches we measure the spatio-temporal structure of baseline
      activity and of auditory evoked responses in identified populations of HVC cells.
      We find strong correlations between calcium signal fluctuations in nearby cells
      of a given type, both in identified neurons and in astroglia. In identified HVC
      neurons only, auditory stimulation decorrelates ongoing calcium signals, less for
      BOS than for other sound stimuli. Overall, calcium transients show strong
      preference for BOS in identified HVC neurons but not in astroglia, showing
      diversity in local functional organization among identified neuron and astroglia
      populations. 

PMID- 24312534
TI  - Survival of Escherichia coli O157:H7 in soils from Jiangsu Province, China.
AB  - Escherichia coli O157:H7 (E. coli O157:H7) is recognized as a hazardous
      microorganism in the environment and for public health. The E. coli O157:H7
      survival dynamics were investigated in 12 representative soils from Jiangsu
      Province, where the largest E. coli O157:H7 infection in China occurred. It was
      observed that E. coli O157:H7 declined rapidly in acidic soils (pH, 4.57 - 5.14)
      but slowly in neutral soils (pH, 6.51 - 7.39). The survival dynamics were well
      described by the Weibull model, with the calculated td value (survival time of
      the culturable E. coli O157:H7 needed to reach the detection limit of 100 CFU g(
      1)) from 4.57 days in an acidic soil (pH, 4.57) to 34.34 days in a neutral soil
      (pH, 6.77). Stepwise multiple regression analysis indicated that soil pH and soil
      organic carbon favored E. coli O157:H7 survival, while a high initial ratio of
      Gram-negative bacteria phospholipid fatty acids (PLFAs) to Gram-positive bacteria
      PLFAs, and high content of exchangeable potassium inhibited E. coli O157:H7
      survival. Principal component analysis clearly showed that the survival profiles
      in soils with high pH were different from those with low pH. 

PMID- 24312536
TI  - CNVs-microRNAs interactions demonstrate unique characteristics in the human
      genome. An interspecies in silico analysis.
AB  - MicroRNAs (miRNAs) and copy number variations (CNVs) represent two classes of
      newly discovered genomic elements that were shown to contribute to genome
      plasticity and evolution. Recent studies demonstrated that miRNAs and CNVs must
      have co-evolved and interacted in an attempt to maintain the balance of the
      dosage sensitive genes and at the same time increase the diversity of dosage non
      sensitive genes, contributing to species evolution. It has been previously
      demonstrated that both the number of miRNAs that target genes found in CNV
      regions as well as the number of miRNA binding sites are significantly higher
      than those of genes found in non-CNV regions. These findings raise the
      possibility that miRNAs may have been created under evolutionary pressure, as a
      mechanism for increasing the tolerance to genome plasticity. In the current
      study, we aimed in exploring the differences of miRNAs-CNV functional
      interactions between human and seven others species. By performing in silico
      whole genome analysis in eight different species (human, chimpanzee, macaque,
      mouse, rat, chicken, dog and cow), we demonstrate that miRNAs targeting genes
      located within CNV regions in humans have special functional characteristics that
      provide an insight into the differences between humans and other species. 

PMID- 24312535
TI  - Endothelial transmigration by Trypanosoma cruzi.
AB  - Chagas heart disease, the leading cause of heart failure in Latin America,
      results from infection with the parasite Trypanosoma cruzi. Although T. cruzi
      disseminates intravascularly, how the parasite contends with the endothelial
      barrier to escape the bloodstream and infect tissues has not been described.
      Understanding the interaction between T. cruzi and the vascular endothelium,
      likely a key step in parasite dissemination, could inform future therapies to
      interrupt disease pathogenesis. We adapted systems useful in the study of
      leukocyte transmigration to investigate both the occurrence of parasite
      transmigration and its determinants in vitro. Here we provide the first evidence
      that T. cruzi can rapidly migrate across endothelial cells by a mechanism that is
      distinct from productive infection and does not disrupt monolayer integrity or
      alter permeability. Our results show that this process is facilitated by a known
      modulator of cellular infection and vascular permeability, bradykinin, and can be
      augmented by the chemokine CCL2. These represent novel findings in our
      understanding of parasite dissemination, and may help identify new therapeutic
      strategies to limit the dissemination of the parasite. 

PMID- 24312538
TI  - The effects of operational conditions on the respiration rate of Tubificidae.
AB  - Tubificidae is often used in the wastewater treatment systems to minimize the
      sludge production because it can be fed on the activated sludge. The process
      conditions have effect on the growth, reproduction, and sludge reduction
      efficiency of Tubificidae. The effects of the water quality, density of worms,
      pH, temperature and dissolved oxygen (DO) concentration on the respiration rate
      of Tubificidae were investigated to determine the optimal conditions for the
      growth and metabolism of the worms and reveal the mechanisms involving the
      efficient sludge reduction in terms of these conditions. It was observed that the
      respiration rate was highest in the water discharged from an ecosystem that
      included symbiotic Tubificidae and microbes and was lowest in distilled water.
      Considering density of the worms, the highest rate was 81.72+/-5.12 mg O2/g(dry
      weight).h.L with 0.25 g (wet weight) of worms in 1 L test flask. The maximum
      Tubificidae respiration rate was observed at a pH of 8.0+/-0.05, a rate that was
      more than twice as high as those observed at other pH values. The respiration
      rate increased in the temperature range of ~8 degrees C-22 degrees C, whereas the
      rate declined in the temperature range of ~22 degrees C-30 degrees C. The
      respiration rate of Tubificidae was very high for DO range of ~3.5-4.5 mg/L, and
      the rates were relatively low for out of this DO range. The results of this study
      revealed the process conditions which influenced the growth, and reproduction of
      Tubificidae and sludge reduction at a microscopic level, which could be a
      theoretical basis for the cultivation and application of Tubificidae in
      wastewater treatment plants. 

PMID- 24312537
TI  - Use of anti-Aedes aegypti salivary extract antibody concentration to correlate
      risk of vector exposure and dengue transmission risk in Colombia.
AB  - Norte de Santander is a region in Colombia with a high incidence of dengue virus
      (DENV). In this study, we examined the serum concentration of anti-Aedes salivary
      gland extract (SGE) antibodies as a biomarker of DENV infection and transmission,
      and assessed the duration of anti-SGE antibody concentration after exposure to
      the vector ceased. We also determined whether SGE antibody concentration could
      differentiate between positive and negative DENV infected individuals and whether
      there are differences in exposure for each DENV serotype. We observed a
      significant decrease in the concentration of IgG antibodies at least 40 days
      after returning to an "Ae. aegypti-free" area. In addition, we found
      significantly higher anti-SGE IgG concentrations in DENV positive patients with
      some difference in exposure to mosquito bites among DENV serotypes. We conclude
      that the concentration of IgG antibodies against SGE is an accurate indicator of
      risk of dengue virus transmission and disease presence. 

PMID- 24312539
TI  - ZAP-70 promotes the infiltration of malignant B-lymphocytes into the bone marrow
      by enhancing signaling and migration after CXCR4 stimulation.
AB  - ZAP-70 in chronic lymphocytic leukemia (CLL) is associated with enhanced response
      to microenvironmental stimuli. We analyzed the functional consequences of ZAP-70
      ectopic expression in malignant B-cells in a xenograft mouse model of
      disseminated B-cell leukemia. Mice injected with B-cells expressing ZAP-70 showed
      a prominently higher infiltration of the bone marrow. In vitro analysis of the
      response of malignant B-cells to CXCL12, the main attracting chemokine regulating
      trafficking of lymphocytes to the bone marrow, or to bone marrow stromal cells,
      revealed that ZAP-70 induces an increased response in terms of signaling and
      migration. These effects are probably mediated by direct participation of ZAP-70
      in CXCL12-CXCR4 signaling since CXCR4 stimulation led to activation of ZAP-70 and
      downstream signaling pathways, such as MAPK and Akt, whereas ZAP-70 did not alter
      the expression of the CXCR4 receptor. In addition, subclones of primary CLL cells
      with high expression of ZAP-70 also showed increased migrative capacity toward
      CXCL12. Neutralization of CXCR4 with a monoclonal antibody resulted in impaired
      in vitro responses to CXCL12 and bone marrow stromal cells. We conclude that ZAP
      70 enhances the migration of malignant B-cells into the supportive
      microenvironment found in the bone marrow mainly by enhancing signaling and
      migration after CXCR4 stimulation. 

PMID- 24312540
TI  - An optimal cost effectiveness study on Zimbabwe cholera seasonal data from 2008
      2011.
AB  - Incidence of cholera outbreak is a serious issue in underdeveloped and developing
      countries. In Zimbabwe, after the massive outbreak in 2008-09, cholera cases and
      deaths are reported every year from some provinces. Substantial number of
      reported cholera cases in some provinces during and after the epidemic in 2008-09
      indicates a plausible presence of seasonality in cholera incidence in those
      regions. We formulate a compartmental mathematical model with periodic slow-fast
      transmission rate to study such recurrent occurrences and fitted the model to
      cumulative cholera cases and deaths for different provinces of Zimbabwe from the
      beginning of cholera outbreak in 2008-09 to June 2011. Daily and weekly reported
      cholera incidence data were collected from Zimbabwe epidemiological bulletin,
      Zimbabwe Daily cholera updates and Office for the Coordination of Humanitarian
      Affairs Zimbabwe (OCHA, Zimbabwe). For each province, the basic reproduction
      number ([Formula: see text]) in periodic environment is estimated. To the best of
      our knowledge, this is probably a pioneering attempt to estimate [Formula: see
      text] in periodic environment using real-life data set of cholera epidemic for
      Zimbabwe. Our estimates of [Formula: see text] agree with the previous estimate
      for some provinces but differ significantly for Bulawayo, Mashonaland West,
      Manicaland, Matabeleland South and Matabeleland North. Seasonal trend in cholera
      incidence is observed in Harare, Mashonaland West, Mashonaland East, Manicaland
      and Matabeleland South. Our result suggests that, slow transmission is a
      dominating factor for cholera transmission in most of these provinces. Our model
      projects [Formula: see text] cholera cases and [Formula: see text] cholera deaths
      during the end of the epidemic in 2008-09 to January 1, 2012. We also determine
      an optimal cost-effective control strategy among the four government undertaken
      interventions namely promoting hand-hygiene & clean water distribution,
      vaccination, treatment and sanitation for each province. 

PMID- 24312541
TI  - Plasma B-type natriuretic peptide as a predictor of cardiovascular events in
      subjects with atrial fibrillation: a community-based study.
AB  - OBJECTIVES: Atrial fibrillation (AF) is a significant public health issue due to
      its high prevalence in the general population, and is associated with an
      increased risk of cardiovascular (CV) events including systemic thrombo-embolism,
      heart failure, and coronary artery disease. The relationship between plasma B
      type natriuretic peptide (BNP) and CV risk in real world AF subjects remains
      unknown. METHODS: The subject of the study (n = 228; mean age = 69 years) was
      unselected individuals with AF in a community-based population (n = 15,394; AF
      prevalence rate = 1.5%). The CV event free rate within each BNP tertile was
      estimated, and Cox regression analysis was performed to examine the relative risk
      of the onset of CV events among the tertiles. The prognostic ability of BNP was
      compared to an established risk score for embolic events (CHADS2 score). In
      addition, to determine the usefulness of BNP as a predictor in addition to CHADS2
      score, we calculated Net Reclassification Improvement (NRI) and Integrated
      Discrimination Improvement (IDI) indices. RESULTS: During the follow-up period 58
      subjects experienced CV events (52 per 1,000 person-years). The event-free ratio
      was significantly lower in the highest tertile (p < 0.02). After adjustment for
      established CV risk factors, the hazard ratio (HR) of the highest tertile was
      significantly higher than that of the lowest tertile (HR = 2.38; p < 0.02). The
      predictive abilities of plasma BNP in terms of sensitivity and specificity for
      general CV events were comparable to those of CHADS2 score. Adding BNP to the
      CHADS2 score only model improved the NRI (0.319; p < 0.05) and the IDI (0.046; p
      < 0.05). CONCLUSION: Plasma BNP is a valuable biomarker both singly or in
      combination with an established scoring system for assessing general CV risk
      including stroke, heart failure and acute coronary syndrome in real-world AF
      subjects.

PMID- 24312542
TI  - Spatial and temporal variations in stable carbon (delta(13)C) and nitrogen
      (delta(15)N) isotopic composition of symbiotic scleractinian corals.
AB  - Tropical scleractinian corals are considered autotrophic as they rely mainly on
      photosynthesis-derived nutrients transferred from their photosymbionts. Corals
      are also able to capture and ingest suspended particulate organic matter, so
      heterotrophy can be an important supplementary trophic pathway to optimize coral
      fitness. The aim of this in situ study was to elucidate the trophic status of 10
      coral species under contrasted environmental conditions in a French Polynesian
      lagoon. Carbon (delta(13)C) and nitrogen (delta(15)N) isotopic compositions of
      coral host tissues and photosymbionts were determined at 3 different fringing
      reefs during wet and dry seasons. Our results highlighted spatial variability in
      stable isotopic compositions of both coral host tissues and photosymbionts.
      Samples from the site with higher level of suspended particulate matter were
      (13)C-depleted and (15)N-enriched relative to corals and photosymbionts from less
      turbid sites. However, differences in both delta(13)C and delta(15)N between
      coral host tissues and their photosymbionts (Delta(host-photosymbionts 13)C and
      Delta(host-photosymbionts 15)N) were small (0.27 +/- 0.760/00 and 1.40 +/-
      0.900/00, respectively) and similar at all sites, thus indicating no general
      increases in the heterotrophic pathway. Depleted delta(13)C and enriched
      delta(15)N values of coral host tissues measured at the most turbid site were
      explained by changes in isotopic composition of the inorganic nutrients taken up
      by photosymbionts and also by changes in rate of isotopic fractionation with
      environmental conditions. Our results also highlighted a lack of significant
      temporal variations in delta(13)C and delta(15)N values of coral host and
      photosymbiont tissues and in Delta(host-photosymbionts 13)C and Delta(host
      photosymbionts 15)N values. This temporal stability indicated that corals
      remained principally autotrophic even during the wet season when photosymbiont
      densities were lower and the concentrations of phytoplankton were higher.
      Increased coral heterotrophy with higher food availability thus appears to be
      species-specific. 

PMID- 24312544
TI  - Protein phosphatases decrease their activity during capacitation: a new
      requirement for this event.
AB  - There are few reports on the role of protein phosphatases during capacitation.
      Here, we report on the role of PP2B, PP1, and PP2A during human sperm
      capacitation. Motile sperm were resuspended in non-capacitating medium (NCM,
      Tyrode's medium, albumin- and bicarbonate-free) or in reconstituted medium (RCM,
      NCM plus 2.6% albumin/25 mM bicarbonate). The presence of the phosphatases was
      evaluated by western blotting and the subcellular localization by indirect
      immunofluorescence. The function of these phosphatases was analyzed by incubating
      the sperm with specific inhibitors: okadaic acid, I2, endothall, and
      deltamethrin. Different aliquots were incubated in the following media: 1) NCM;
      2) NCM plus inhibitors; 3) RCM; and 4) RCM plus inhibitors. The percent
      capacitated sperm and phosphatase activities were evaluated using the
      chlortetracycline assay and a phosphatase assay kit, respectively. The results
      confirm the presence of PP2B and PP1 in human sperm. We also report the presence
      of PP2A, specifically, the catalytic subunit and the regulatory subunits PR65 and
      B. PP2B and PP2A were present in the tail, neck, and postacrosomal region, and
      PP1 was present in the postacrosomal region, neck, middle, and principal piece of
      human sperm. Treatment with phosphatase inhibitors rapidly (<=1 min) increased
      the percent of sperm depicting the pattern B, reaching a maximum of ~40% that was
      maintained throughout incubation; after 3 h, the percent of capacitated sperm was
      similar to that of the control. The enzymatic activity of the phosphatases
      decreased during capacitation without changes in their expression. The pattern of
      phosphorylation on threonine residues showed a sharp increase upon treatment with
      the inhibitors. In conclusion, human sperm express PP1, PP2B, and PP2A, and the
      activity of these phosphatases decreases during capacitation. This decline in
      phosphatase activities and the subsequent increase in threonine phosphorylation
      may be an important requirement for the success of sperm capacitation. 

PMID- 24312543
TI  - Prevalence and trends of the abdominal aortic aneurysms epidemic in general
      population--a meta-analysis.
AB  - OBJECTIVE: To conduct a meta-analysis assessing the prevalence and trends of the
      abdominal aortic aneurysms (AAA) epidemic in general population. METHOD: Studies
      that reported prevalence rates of AAA from the general population were identified
      through MEDLINE, EMBASE, Web of Science, and reference lists for the period
      between 1988 and 2013. Studies were included if they reported prevalence rates of
      AAA in general population from the community. In stratified analyses possible
      sources of bias, including areas difference, age, gender and diameter of
      aneurysms were examined. Publication bias was assessed with Egger's test method.
      RESULTS: 56 studies were identified. The overall pooled prevalence of AAA was
      4.8% (4.3%, 5.3%). Stratified analyses showed the following results, areas
      difference: America 2.2% (2.2%, 2.2%), Europe 2.5% (2.4%, 2.5%), Australia 6.7%
      (6.5%, 7.0%), Asia 0.5% (0.3%, 0.7%); gender difference: male 6.0% (5.3%, 6.7%),
      female 1.6% (1.2%, 1.9%); age difference: 55-64years 1.3% (1.2%, 1.5%), 65-74
      years 2.8% (2.7%, 2.9%), 75-84 years1.2%(1.1%, 1.3%), >=85years0.6% (0.4%, 0.7%);
      aortic diameters difference: 30-39 mm, 3.3% (2.8%, 3.9%), 40-49 mm,0.7%
      (0.4%,1.0%), >=50 mm, 0.4% (0.3%, 0.5%). The prevalence of AAA has decreased in
      Europe from 1988 to 2013. Hypertension, smoking, coronary artery disease,
      dyslipidemia, respiratory disease, cerebrovascular disease, claudication and
      renal insufficiency were risk factors for AAA in Europe. CONCLUSION: AAA is
      common in general population. The prevalence of AAA is higher in Australia than
      America and Europe. The pooled prevalence in western countries is higher than the
      Asia. Future research requires a larger database on the epidemiology of AAA in
      general population.

PMID- 24312546
TI  - Genetic diversity of food-isolated Salmonella strains through Pulsed Field Gel
      Electrophoresis (PFGE) and Enterobacterial Repetitive Intergenic Consensus (ERIC
      PCR).
AB  - All over the world, the incidence of Salmonella spp contamination on different
      food sources like broilers, clams and cow milk has increased rapidly in recent
      years. The multifaceted properties of Salomnella serovars allow the microorganism
      to grow and multiply in various food matrices, even under adverse conditions.
      Therefore, methods are needed to detect and trace this pathogen along the entire
      food supply network. In the present work, PFGE and ERIC-PCR were used to subtype
      45 Salmonella isolates belonging to different serovars and derived from different
      food origins. Among these isolates, S. Enteritidis and S. Kentucky were found to
      be the most predominant serovars. The Discrimination Index obtained by ERIC-PCR
      (0.85) was slightly below the acceptable confidence value. The best
      discriminatory ability was observed when PFGE typing method was used alone (DI =
      0.94) or combined with ERIC-PCR (DI = 0.93). A wide variety of profiles was
      observed between the different serovars using PFGE or/and ERIC-PCR. This
      diversity is particularly important when the sample origins are varied and even
      within the same sampling origin. 

PMID- 24312545
TI  - Exclusive breastfeeding, diarrhoeal morbidity and all-cause mortality in infants
      of HIV-infected and HIV uninfected mothers: an intervention cohort study in
      KwaZulu Natal, South Africa.
AB  - INTRODUCTION: Antiretroviral drug interventions significantly reduce the risk of
      HIV transmission to infants through breastfeeding. We report diarrhoea prevalence
      and all-cause mortality at 12 months of age according to infant feeding
      practices, among infants born to HIV-infected and uninfected mothers in South
      Africa. METHODS: A non-randomised intervention cohort study that followed both
      HIV-infected and HIV-uninfected mothers and their infants until 18 months of age.
      Mothers were supported in their infant feeding choice. Detailed morbidity and
      vital status data were collected over the first year. At the time, only single
      dose nevirapine was available to prevent mother-to-child transmission of HIV.
      RESULTS: Among 2,589 infants, detailed feeding data and vital status were
      available for 1,082 HIV-exposed infants and 1,155 HIV non-exposed infants. Among
      exclusively breastfed (EBF) infants there were 9.4 diarrhoeal days per 1,000
      child days (95%CI. 9.12-9.82) while among infants who were never breastfed there
      were 15.6 diarrhoeal days per 1,000 child days (95%CI. 14.62-16.59). Exclusive
      breastfeeding was associated with fewer acute, persistent and total diarrhoeal
      events than mixed or no breastfeeding in both HIV-exposed infants and also
      infants of HIV uninfected mothers. In an adjusted cox regression analysis, the
      risk of death among all infants by 12 months of age was significantly greater in
      those who were never breastfed (aHR 3.5, p<0.001) or mixed fed (aHR 2.65,
      p<0.001) compared with those who were EBF. In separate multivariable analyses,
      infants who were EBF for shorter durations had an increased risk of death
      compared to those EBF for 5-6 months [aHR 2.18 (95% CI, 1.56-3.01); p<0.001].
      DISCUSSION: In the context of antiretroviral drugs being scaled-up to eliminate
      new HIV infections among children, there is strong justification for financial
      and human resource investment to promote and support exclusive breastfeeding to
      improve HIV-free survival of HIV-exposed and non-exposed infants.

PMID- 24312547
TI  - Hydrodynamic characteristics of the sailfish (Istiophorus platypterus) and
      swordfish (Xiphias gladius) in gliding postures at their cruise speeds.
AB  - The sailfish and swordfish are known as the fastest sea animals, reaching their
      maximum speeds of around 100 km/h. In the present study, we investigate the
      hydrodynamic characteristics of these fishes in their cruise speeds of about 1
      body length per second. We install a taxidermy specimen of each fish in a wind
      tunnel, and measure the drag on its body and boundary-layer velocity above its
      body surface at the Reynolds number corresponding to its cruising condition. The
      drag coefficients of the sailfish and swordfish based on the free-stream velocity
      and their wetted areas are measured to be 0.0075 and 0.0091, respectively, at
      their cruising conditions. These drag coefficients are very low and comparable to
      those of tuna and pike and smaller than those of dogfish and small-size trout. On
      the other hand, the long bill is one of the most distinguished features of these
      fishes from other fishes, and we study its role on the ability of drag
      modification. The drag on the fish without the bill or with an artificially-made
      shorter one is slightly smaller than that with the original bill, indicating that
      the bill itself does not contribute to any drag reduction at its cruise speed.
      From the velocity measurement near the body surface, we find that at the cruise
      speed flow separation does not occur over the whole body even without the bill,
      and the boundary layer flow is affected only at the anterior part of the body by
      the bill. 

PMID- 24312548
TI  - Anti-remodeling effects of rapamycin in experimental heart failure: dose response
      and interaction with angiotensin receptor blockade.
AB  - While neurohumoral antagonists improve outcomes in heart failure (HF), cardiac
      remodeling and dysfunction progress and outcomes remain poor. Therapies superior
      or additive to standard HF therapy are needed. Pharmacologic mTOR inhibition by
      rapamycin attenuated adverse cardiac remodeling and dysfunction in experimental
      heart failure (HF). However, these studies used rapamycin doses that produced
      blood drug levels targeted for primary immunosuppression in human transplantation
      and therefore the immunosuppressive effects may limit clinical translation.
      Further, the relative or incremental effect of rapamycin combined with standard
      HF therapies targeting upstream regulators of cardiac remodeling (neurohumoral
      antagonists) has not been defined. Our objectives were to determine if anti
      remodeling effects of rapamycin were preserved at lower doses and whether
      rapamycin effects were similar or additive to a standard HF therapy (angiotensin
      receptor blocker (losartan)). Experimental murine HF was produced by transverse
      aortic constriction (TAC). At three weeks post-TAC, male mice with established HF
      were treated with placebo, rapamycin at a dose producing immunosuppressive drug
      levels (target dose), low dose (50% target dose) rapamycin, losartan or rapamycin
      + losartan for six weeks. Cardiac structure and function (echocardiography,
      catheterization, pathology, hypertrophic and fibrotic gene expression profiles)
      were assessed. Downstream mTOR signaling pathways regulating protein synthesis
      (S6K1 and S6) and autophagy (LC3B-II) were characterized. TAC-HF mice displayed
      eccentric hypertrophy, systolic dysfunction and pulmonary congestion. These
      perturbations were attenuated to a similar degree by oral rapamycin doses
      achieving target (13.3+/-2.1 ng/dL) or low (6.7+/-2.5 ng/dL) blood levels.
      Rapamycin treatment decreased mTOR mediated regulators of protein synthesis and
      increased mTOR mediated regulators of autophagy. Losartan monotherapy did not
      attenuate remodeling, whereas Losartan added to rapamycin provided no incremental
      benefit over rapamycin alone. These data lend support to investigation of low
      dose rapamycin as a novel therapy in human HF. 

PMID- 24312549
TI  - Parafoveal retinal vascular response to pattern visual stimulation assessed with
      OCT angiography.
AB  - We used optical coherence tomography (OCT) angiography with a high-speed swept
      source OCT system to investigate retinal blood flow changes induced by visual
      stimulation with a reversing checkerboard pattern. The split-spectrum amplitude
      decorrelation angiography (SSADA) algorithm was used to quantify blood flow as
      measured with parafoveal flow index (PFI), which is proportional to the density
      of blood vessels and the velocity of blood flow in the parafoveal region of the
      macula. PFI measurements were taken in 15 second intervals during a 4 minute
      period consisting of 1 minute of baseline, 2 minutes with an 8 Hz reversing
      checkerboard pattern stimulation, and 1 minute without stimulation. PFI
      measurements increased 6.1+/-4.7% (p = .001) during the first minute of
      stimulation, with the most significant increase in PFI occurring 30 seconds into
      stimulation (p<0.001). These results suggest that pattern stimulation induces a
      change to retinal blood flow that can be reliably measured with OCT angiography. 

PMID- 24312550
TI  - Differential contributions of dorso-ventral and rostro-caudal prefrontal white
      matter tracts to cognitive control in healthy older adults.
AB  - Prefrontal cortex mediates cognitive control by means of circuitry organized
      along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis,
      ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes
      task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes
      complex rules and relationships between stimuli, whereas posterior prefrontal
      cortex encodes simple relationships between stimuli and behavior. Evidence of
      these gradients of prefrontal cortex organization has been well documented in
      fMRI studies, but their functional correlates have not been examined with regard
      to integrity of underlying white matter tracts. We hypothesized that (a) the
      integrity of specific white matter tracts is related to cognitive functioning in
      a manner consistent with the dorso-ventral and rostro-caudal organization of the
      prefrontal cortex, and (b) this would be particularly evident in healthy older
      adults. We assessed three cognitive processes that recruit the prefrontal cortex
      and can distinguish white matter tracts along the dorso-ventral and rostro-caudal
      dimensions -episodic memory, working memory, and reasoning. Correlations between
      cognition and fractional anisotropy as well as fiber tractography revealed: (a)
      Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal
      fiber integrity; (b) Working memory was related to integrity of corpus callosum
      body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was
      related to integrity of corpus callosum body fibers subserving rostral and caudal
      dorsolateral prefrontal cortex. These findings confirm the ventrolateral
      prefrontal cortex's role in semantic control and the dorsolateral prefrontal
      cortex's role in rule-based processing, in accordance with the dorso-ventral
      prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal
      white matter may facilitate different levels of task rule complexity. This study
      is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex
      processing gradients in white matter integrity. 

PMID- 24312552
TI  - Genetic variations in COMT and DRD2 modulate attentional bias for affective
      facial expressions.
AB  - Studies have revealed that catechol-O-methyltransferase (COMT) and dopaminegic
      receptor2 (DRD2) modulate human attention bias for palatable food or tobacco.
      However, the existing evidence about the modulations of COMT and DRD2 on
      attentional bias for facial expressions was still limited. In the study, 650
      college students were genotyped with regard to COMT Val158Met and DRD2 TaqI A
      polymorphisms, and the attentional bias for facial expressions was assessed using
      the spatial cueing task. The results indicated that COMT Val158Met underpinned
      the individual difference in attentional bias for negative emotional expressions
      (P = 0.03) and the Met carriers showed more engagement bias for negative
      expressions than the Val/Val homozygote. On the contrary, DRD2 TaqIA underpinned
      the individual difference in attentional bias for positive expressions (P =
      0.003) and individuals with TT genotype showed much more engagement bias for
      positive expressions than the individuals with CC genotype. Moreover, the two
      genes exerted significant interactions on the engagements for negative and
      positive expressions (P = 0.046, P = 0.005). These findings suggest that the
      individual differences in the attentional bias for emotional expressions are
      partially underpinned by the genetic polymorphisms in COMT and DRD2. 

PMID- 24312551
TI  - Enteric neuropathy can be induced by high fat diet in vivo and palmitic acid
      exposure in vitro.
AB  - OBJECTIVE: Obese and/or diabetic patients have elevated levels of free fatty
      acids and increased susceptibility to gastrointestinal symptoms. Since the
      enteric nervous system is pivotal in regulating gastrointestinal functions
      alterations or neuropathy in the enteric neurons are suspected to occur in these
      conditions. Lipid induced intestinal changes, in particular on enteric neurons,
      were investigated in vitro and in vivo using primary cell culture and a high fat
      diet (HFD) mouse model. DESIGN: Mice were fed normal or HFD for 6 months.
      Intestines were analyzed for neuronal numbers, remodeling and lipid accumulation.
      Co-cultures of myenteric neurons, glia and muscle cells from rat small intestine,
      were treated with palmitic acid (PA) (0 - 10(-3) M) and / or oleic acid (OA) (0 -
      10(-3) M), with or without modulators of intracellular lipid metabolism. Analyses
      were by immunocyto- and histochemistry. RESULTS: HFD caused substantial loss of
      myenteric neurons, leaving submucous neurons unaffected, and intramuscular lipid
      accumulation in ileum and colon. PA exposure in vitro resulted in neuronal
      shrinkage, chromatin condensation and a significant and concentration-dependent
      decrease in neuronal survival; OA exposure was neuroprotective. Carnitine
      palmitoyltransferase 1 inhibition, L-carnitine- or alpha lipoic acid
      supplementation all counteracted PA-induced neuronal loss. PA or OA alone both
      caused a significant and concentration-dependent loss of muscle cells in vitro.
      Simultaneous exposure of PA and OA promoted survival of muscle cells and
      increased intramuscular lipid droplet accumulation. PA exposure transformed glia
      from a stellate to a rounded phenotype but had no effect on their survival.
      CONCLUSIONS: HFD and PA exposure are detrimental to myenteric neurons. Present
      results indicate excessive palmitoylcarnitine formation and exhausted L-carnitine
      stores leading to energy depletion, attenuated acetylcholine synthesis and
      oxidative stress to be main mechanisms behind PA-induced neuronal loss.High PA
      exposure is suggested to be a factor in causing diabetic neuropathy and
      gastrointestinal dysregulation.

PMID- 24312553
TI  - Metabolic footprint analysis uncovers strain specific overflow metabolism and D
      isoleucine production of Staphylococcus aureus COL and HG001.
AB  - During infection processes, Staphylococcus aureus is able to survive within the
      host and to invade tissues and cells. For studying the interaction between the
      pathogenic bacterium and the host cell, the bacterial growth behaviour and its
      metabolic adaptation to the host cell environment provides first basic
      information. In the present study, we therefore cultivated S. aureus COL and
      HG001 in the eukaryotic cell culture medium RPMI 1640 and analyzed the
      extracellular metabolic uptake and secretion patterns of both commonly used
      laboratory strains. Extracellular accumulation of D-isoleucine was detected
      starting during exponential growth of COL and HG001 in RPMI medium. This non
      canonical D-amino acid is known to play a regulatory role in adaptation
      processes. Moreover, individual uptake of glucose, accumulation of acetate,
      further overflow metabolites, and intermediates of the branched-chain amino acid
      metabolism constitute unique metabolic footprints. Altogether these time-resolved
      footprint analyses give first metabolic insights into staphylococcal growth
      behaviour in a culture medium used for infection related studies. 

PMID- 24312554
TI  - Bradykinin preconditioning improves therapeutic potential of human endothelial
      progenitor cells in infarcted myocardium.
AB  - OBJECTIVES: Stem cell preconditioning (PC) is a powerful approach in reducing
      cell death after transplantation. We hypothesized that PC human endothelial
      progenitor cells (hEPCs) with bradykinin (BK) enhance cell survival, inhibit
      apoptosis and repair the infarcted myocardium. METHODS: The hEPCs were
      preconditioned with or without BK. The hEPCs apoptosis induced by hypoxia along
      with serum deprivation was determined by annexin V-fluorescein isothiocyanate/
      propidium iodide staining. Cleaved caspase-3, Akt and eNOS expressions were
      determined by Western blots. Caspase-3 activity and vascular endothelial growth
      factor (VEGF) levels were assessed in hEPCs. For in vivo studies, the survival
      and cardiomyocytes apoptosis of transplanted hEPCs were assessed using 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindodi- carbocyanine,4-chlorobenzenesul-fonate
      salt labeled hEPCs and TUNEL staining. Infarct size and cardiac function were
      measured at 10 days after transplantation, and the survival of transplanted hEPCs
      were visualized using near-infrared optical imaging. RESULTS: In vitro data
      showed a marked suppression in cell apoptosis following BK PC. The PC reduced
      caspase-3 activation, increased the Akt, eNOS phosphorylation and VEGF levels. In
      vivo data in preconditioned group showed a robust cell anti-apoptosis, reduction
      in infarct size, and significant improvement in cardiac function. The effects of
      BK PC were abrogated by the B2 receptor antagonist HOE140, the Akt and eNOS
      antagonists LY294002 and L-NAME, respectively. CONCLUSIONS: The activation of B2
      receptor-dependent PI3K/Akt/eNOS pathway by BK PC promotes VEGF secretion, hEPC
      survival and inhibits apoptosis, thereby improving cardiac function in vivo. The
      BK PC hEPC transplantation for stem cell-based therapies is a novel approach that
      has potential for clinical used.

PMID- 24312555
TI  - Role of N-cadherin cis and trans interfaces in the dynamics of adherens junctions
      in living cells.
AB  - Cadherins, Ca(2+)-dependent adhesion molecules, are crucial for cell-cell
      junctions and remodeling. Cadherins form inter-junctional lattices by the
      formation of both cis and trans dimers. Here, we directly visualize and quantify
      the spatiotemporal dynamics of wild-type and dimer mutant N-cadherin interactions
      using time-lapse imaging of junction assembly, disassembly and a FRET reporter to
      assess Ca(2+)-dependent interactions. A trans dimer mutant (W2A) and a cis mutant
      (V81D/V174D) exhibited an increased Ca(2+)-sensitivity for the disassembly of
      trans dimers compared to the WT, while another mutant (R14E) was insensitive to
      Ca(2+)-chelation. Time-lapse imaging of junction assembly and disassembly,
      monitored in 2D and 3D (using cellular spheroids), revealed kinetic differences
      in the different mutants as well as different behaviors in the 2D and 3D
      environment. Taken together, these data provide new insights into the role that
      the cis and trans dimers play in the dynamic interactions of cadherins. 

PMID- 24312556
TI  - Subunit organisation of in vitro reconstituted HOPS and CORVET multisubunit
      membrane tethering complexes.
AB  - Biochemical and structural analysis of macromolecular protein assemblies remains
      challenging due to technical difficulties in recombinant expression, engineering
      and reconstitution of multisubunit complexes. Here we use a recently developed
      cell-free protein expression system based on the protozoan Leishmania tarentolae
      to produce in vitro all six subunits of the 600 kDa HOPS and CORVET membrane
      tethering complexes. We demonstrate that both subcomplexes and the entire HOPS
      complex can be reconstituted in vitro resulting in a comprehensive subunit
      interaction map. To our knowledge this is the largest eukaryotic protein complex
      in vitro reconstituted to date. Using the truncation and interaction analysis, we
      demonstrate that the complex is assembled through short hydrophobic sequences
      located in the C-terminus of the individual Vps subunits. Based on this data we
      propose a model of the HOPS and CORVET complex assembly that reconciles the
      available biochemical and structural data. 

PMID- 24312557
TI  - A new barrier to dispersal trapped old genetic clines that escaped the Easter
      Microplate tension zone of the Pacific vent mussels.
AB  - Comparative phylogeography of deep-sea hydrothermal vent species has uncovered
      several genetic breaks between populations inhabiting northern and southern
      latitudes of the East Pacific Rise. However, the geographic width and position of
      genetic clines are variable among species. In this report, we further
      characterize the position and strength of barriers to gene flow between
      populations of the deep-sea vent mussel Bathymodiolus thermophilus. Eight
      allozyme loci and DNA sequences of four nuclear genes were added to previously
      published sequences of the cytochrome c oxidase subunit I gene. Our data confirm
      the presence of two barriers to gene flow, one located at the Easter Microplate
      (between 21 degrees 33'S and 31 degrees S) recently described as a hybrid zone,
      and the second positioned between 7 degrees 25'S and 14 degrees S with each
      affecting different loci. Coalescence analysis indicates a single vicariant event
      at the origin of divergence between clades for all nuclear loci, although the
      clines are now spatially discordant. We thus hypothesize that the Easter
      Microplate barrier has recently been relaxed after a long period of isolation and
      that some genetic clines have escaped the barrier and moved northward where they
      have subsequently been trapped by a reinforcing barrier to gene flow between 7
      degrees 25'S and 14 degrees S. 

PMID- 24312558
TI  - BtcA, A class IA type III chaperone, interacts with the BteA N-terminal domain
      through a globular/non-globular mechanism.
AB  - Bordetella pertussis, the etiological agent of "whooping cough" disease, utilizes
      the type III secretion system (T3SS) to deliver a 69 kDa cytotoxic effector
      protein, BteA, directly into the host cells. As with other T3SS effectors, prior
      to its secretion BteA binds BtcA, a 13.9 kDa protein predicted to act as a T3SS
      class IA chaperone. While this interaction had been characterized for such
      effector-chaperone pairs in other pathogens, it has yet to be fully investigated
      in Bordetella. Here we provide the first biochemical proof that BtcA is indeed a
      class IA chaperone, responsible for the binding of BteA's N-terminal domain. We
      bring forth extensive evidence that BtcA binds its substrate effector through a
      dual-interface binding mechanism comprising of non-globular and bi-globular
      interactions at a moderate micromolar level binding affinity. We demonstrate that
      the non-globular interactions involve the first 31 N-terminal residues of BteA287
      and their removal leads to destabilization of the effector-chaperone complex and
      lower binding affinities to BtcA. These findings represent an important first
      step towards a molecular understanding of BteA secretion and cell entry. 

PMID- 24312559
TI  - Converting a microarray signature into a diagnostic test: a trial of custom 74
      gene array for clarification and prediction the prognosis of gastric cancer.
AB  - BACKGROUND: Gastric cancer (GC) is associated with high mortality rates and an
      unfavorable prognosis at advanced stages. In addition, there are no effective
      methods for diagnosing gastric cancer at an early stage or for predicting the
      outcome for the purpose of selecting patient-specific treatment options.
      Therefore, it is important to investigate new methods for GC diagnosis.
      METHODOLOGY/PRINCIPAL FINDINGS: To facilitate its use in a diagnostic setting, a
      group of 74 genes with diagnostic and prognostic information was translated into
      a customized microarray containing a reduced set of 1,042 probes suitable for
      high throughput processing. In this report, we demonstrate for the first time
      that the custom mini-array can be used as a reliable diagnostic tool in gastric
      cancer. With an AUC value of 0.565 (95% CI 0.305-0.825) indicating a perfect
      test, the sensitivity and specificity of diagnosis from the ROC curve were
      calculated to be 70% and 80%, respectively. CONCLUSIONS/SIGNIFICANCE: The data
      clearly demonstrate the reproducibility and robustness of the small custom-made
      microarray. The array is an excellent tool for classifying and predicting the
      outcome of disease in gastric cancer patients.

PMID- 24312560
TI  - RhoC interacts with integrin alpha5beta1 and enhances its trafficking in
      migrating pancreatic carcinoma cells.
AB  - Human pancreatic ductal adenocarcinoma (PDAC) is characterized by early systemic
      dissemination. Although RhoC has been implicated in cancer cell migration, the
      relevant underlying molecular mechanisms remain unknown. RhoC has been implicated
      in the enhancement of cancer cell migration and invasion, with actions which are
      distinct from RhoA (84% homology), and are possibly attributed to the divergent C
      terminus domain. Here, we confirm that RhoC significantly enhances the migratory
      and invasive properties of pancreatic carcinoma cells. In addition, we show that
      RhoC over-expression decreases cancer cell adhesion and, in turn, accelerates
      cellular body movement and focal adhesion turnover, especially, on fibronectin
      coated surfaces. Whilst RhoC over-expression did not alter integrin expression
      patterns, we show that it enhanced integrin alpha5beta1 internalization and re
      cycling (trafficking), an effect that was dependent specifically on the C
      terminus (180-193 amino acids) of RhoC protein. We also report that RhoC and
      integrin alpha5beta1 co-localize within the peri-nuclear region of pancreatic
      tumor cells, and by masking the CAAX motif at the C-terminal of RhoC protein, we
      were able to abolish this interaction in vitro and in vivo. Co-localization of
      integrin alpha5beta1 and RhoC was demonstrable in invading cancer cells in 3D
      organotypic cultures, and further mimicked in vivo analyses of, spontaneous
      human, (two distinct sources: operated patients and rapid autopsy programme) and
      transgenic murine (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre), pancreatic
      cancers. In both cases, co-localization of integrin alpha5beta1 and RhoC
      correlated with poor differentiation status and metastatic potential. We propose
      that RhoC facilitates tumor cell invasion and promotes subsequent metastasis, in
      part, by enhancing integrin alpha5beta1 trafficking. Thus, RhoC may serve as a
      biomarker and a therapeutic target. 

PMID- 24312561
TI  - Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins
      identified by high-throughput screening.
AB  - Overexpressed Human epidermal growth factor receptor 2 (HER2) drives the biology
      of 20% breast cancer and is a prediction of a poor prognosis for patients. HER2
      targeted therapies significantly improve outcomes for HER2-positive patients.
      Traditional Chinese herbs/medicines have been used to treat breast cancer
      patients including HER2-positive patients in Asia for decades. Although the
      traditional medicines demonstrate efficacy in clinics for HER2-positive patients,
      the mechanism is largely unknown. In this article, we screened a 10,000 natural
      product library in 6 different cell lines representing breast cancer, and
      assessed the ability of each drug to cause cytotoxicity through a high-throughput
      screening approach. We have identified eight natural compounds that selectively
      inhibit the proliferation of HER2-positive cells. Two of the hit compounds,
      peonidin-3-glucoside and cyaniding-3-glucoside, are both extracts from black
      rice. They inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce
      HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3
      glucoside and cyaniding-3-glucoside treatments significantly reduced the tumor
      size and volume in vivo compared to the control group. There is no significant
      difference of antitumorgenic effects between peonidin-3-glucoside and cyaniding-3
      glucoside treatments. 

PMID- 24312562
TI  - The dimension of hyoid bone is independently associated with the severity of
      obstructive sleep apnea.
AB  - INTRODUCTION: We hypothesized that the size of the hyoid bone itself may affect
      the severity of sleep apnea. The aim of this study was to identify the
      relationship between hyoid bone dimensions and the severity of sleep apnea using
      computerized tomography (CT) axial images. METHODS: We retrospectively measured
      the hyoid bone in axial images of neck CTs and correlated these measurements with
      results of polysomnography in a total of 106 male patients. The new hyoid bone
      parameters studied in this study were as follows: distance between bilateral
      lesser horns (LH-d), distance between bilateral greater horns (GH-d), distance
      from the most anterior end of the hyoid arch to GH-d (AP), distance from the
      greater to the lesser horn on right and left sides (GH-LH), and the anterior
      angle between bilateral extensive lines from the greater to the lesser horn (H
      angle). Data was analyzed using univariate and multivariate logistic regression,
      and Pearson correlation tests. RESULTS: We found a significant inverse
      correlation between the apnea-hypopnea index (AHI) and GH-d or AP. Neither the LH
      d, GH-LH, nor H-angle were associated with the AHI. The patient group that met
      the criteria of both GH-d<45.4 and AP<33.4 demonstrated the most severe AHI.
      CONCLUSION: The lateral width or antero-posterior length of hyoid bone was
      associated with AHI and predicted the severity of sleep apnea in male patients.
      This finding supports the role of expansion hyoidplasty for treatment of sleep
      apnea. Pre-operative consideration of these parameters may improve surgical
      outcomes in male patients with sleep apnea.

PMID- 24312563
TI  - Number and function of bone-marrow derived angiogenic cells and coronary flow
      reserve in women without obstructive coronary artery disease: a substudy of the
      NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE).
AB  - BACKGROUND: In women with ischemia and no obstructive coronary artery disease,
      the Women's Ischemic Syndrome Evaluation (WISE) observed that microvascular
      coronary dysfunction (MCD) is the best independent predictor of adverse
      cardiovascular events. Since coronary microvascular tone is regulated in part by
      endothelium, we hypothesized that circulating endothelial cells (CEC), which
      reflect endothelial injury, and the number and function of bone-marrow derived
      angiogenic cells (BMDAC), which could help repair damaged endothelium, may serve
      as biomarkers for decreased coronary flow reserve (CFR) and MCD. METHODS: We
      studied 32 women from the WISE cohort. CFR measurements in response to
      intracoronary adenosine were taken as an index of MCD. We enumerated BMDAC
      colonies and CEC in peripheral blood samples. BMDAC function was assessed by
      assay of migration of CD34+ cells toward SDF-1 and measurement of bioavailable
      nitric oxide (NO). These findings were compared with a healthy reference group
      and also entered into a multivariable model with CFR as the dependent variable.
      RESULTS: Compared with a healthy reference group, women with MCD had lower
      numbers of BMDAC colonies [16 (0, 81) vs. 24 (14, 88); P = 0.01] and NO [936
      (156, 1875) vs. 1168 (668, 1823); P = 0.02]. Multivariable regression analysis
      showed strong correlation of CFR to the combination of BMDAC colony count and
      CD34+ cell function (migration and NO) (R(2) = 0.45; P<0.05). CONCLUSIONS: The
      BMDAC function and numbers of BMDAC colonies are decreased in symptomatic women
      with MCD and are independently associated with CFR. These circulating cells may
      provide mechanistic insights into MCD in women with ischemia.

PMID- 24312565
TI  - Meteorological influences on the incidence of aneurysmal subarachnoid hemorrhage 
      a single center study of 511 patients.
AB  - OBJECTIVE: To assess the potential meteorological influence on the incidence of
      aneurysmal subarachnoid hemorrhage (SAH). Previous studies used inhomogeneous
      patient groups, insufficient study periods or inappropriate statistics. PATIENTS
      AND METHODS: We analyzed 511 SAH admissions between 2004 and 2012 for which
      aneurysmal rupture occurred within the Zurich region. The hourly meteorological
      parameters considered are: surface pressure, 2-m temperature, relative humidity
      and wind gusts, sunshine, and precipitation. For all parameters we investigate
      three complementary statistical measures: i) the time evolution from 5 days
      before to 5 days after the SAH occurrence; ii) the deviation from the 10-year
      monthly mean; and iii) the change relative to the parameter's value two days
      before SAH occurrence. The statistical significance of the results is determined
      using a Monte Carlo simulation combined with a re-sampling technique (1000*).
      RESULTS: Regarding the meteorological parameters considered, no statistically
      significant signal could be found. The distributions of deviations relative to
      the climatology and of the changes during the two days prior to SAH events agree
      with the distributions for the randomly chosen days. The analysis was repeated
      separately for winter and summer to exclude compensating effects between the
      seasons. CONCLUSION: By using high-quality meteorological data analyzed with a
      sophisticated and robust statistical method no clearly identifiable
      meteorological influence for the SAH events considered can be found. Further
      studies on the influence of the investigated parameters on SAH incidence seem
      redundant.

PMID- 24312564
TI  - Monoacylglycerols activate TRPV1--a link between phospholipase C and TRPV1.
AB  - Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate
      generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which
      can regulate TRPV1 activity via different mechanisms. Here we explored the
      possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1
      arachidonoylglycerol, and not metabolites of these monoacylglycerols, activate
      TRPV1 and contribute to this signaling cascade. 2-Arachidonoylglycerol and 1
      arachidonoylglycerol activated native TRPV1 on vascular sensory nerve fibers and
      heterologously expressed TRPV1 in whole cells and inside-out membrane patches.
      The monoacylglycerol lipase inhibitors methylarachidonoyl-fluorophosphonate and
      JZL184 prevented the metabolism of deuterium-labeled 2-arachidonoylglycerol and
      deuterium-labeled 1-arachidonoylglycerol in arterial homogenates, and enhanced
      TRPV1-mediated vasodilator responses to both monoacylglycerols. In mesenteric
      arteries from TRPV1 knock-out mice, vasodilator responses to 2
      arachidonoylglycerol were minor. Bradykinin and adenosine triphosphate, ligands
      of phospholipase C-coupled membrane receptors, increased the content of 2
      arachidonoylglycerol in dorsal root ganglia. In HEK293 cells expressing the
      phospholipase C-coupled histamine H1 receptor, exposure to histamine stimulated
      the formation of 2-AG, and this effect was augmented in the presence of JZL184.
      These effects were prevented by the diacylglycerol lipase inhibitor
      tetrahydrolipstatin. Histamine induced large whole cell currents in HEK293 cells
      co-expressing TRPV1 and the histamine H1 receptor, and the TRPV1 antagonist
      capsazepine abolished these currents. JZL184 increased the histamine-induced
      currents and tetrahydrolipstatin prevented this effect. The calcineurin inhibitor
      ciclosporin and the endogenous "entourage" compound palmitoylethanolamide
      potentiated the vasodilator response to 2-arachidonoylglycerol, disclosing TRPV1
      activation of this monoacylglycerol at nanomolar concentrations. Furthermore,
      intracerebroventricular injection of JZL184 produced TRPV1-dependent
      antinociception in the mouse formalin test. Our results show that intact 2
      arachidonoylglycerol and 1-arachidonoylglycerol are endogenous TRPV1 activators,
      contributing to phospholipase C-dependent TRPV1 channel activation and TRPV1
      mediated antinociceptive signaling in the brain. 

PMID- 24312566
TI  - Removal and recovery of toxic silver ion using deep-sea bacterial generated
      biogenic manganese oxides.
AB  - Products containing silver ion (Ag(+)) are widely used, leading to a large amount
      of Ag(+)-containing waste. The deep-sea manganese-oxidizing bacterium
      Marinobacter sp. MnI7-9 efficiently oxidizes Mn(2+) to generate biogenic Mn oxide
      (BMO). The potential of BMO for recovering metal ions by adsorption has been
      investigated for some ions but not for Ag(+). The main aim of this study was to
      develop effective methods for adsorbing and recovering Ag using BMO produced by
      Marinobacter sp. MnI7-9. In addition, the adsorption mechanism was determined
      using X-ray photoelectron spectroscopy analysis, specific surface area analysis,
      adsorption kinetics and thermodynamics. The results showed that BMO had a higher
      adsorption capacity for Ag(+) compared to the chemical synthesized MnO2 (CMO).
      The isothermal absorption curves of BMO and CMO both fit the Langmuir model well
      and the maximum adsorption capacities at 28 degrees C were 8.097 mmol/g and 0.787
      mmol/g, for BMO and CMO, respectively. The change in enthalpy (DeltaH(theta)) for
      BMO was 59.69 kJ/mol indicating that it acts primarily by chemical adsorption.
      The change in free energy (DeltaG(theta)) for BMO was negative, which suggests
      that the adsorption occurs spontaneously. Ag(+) adsorption by BMO was driven by
      entropy based on the positive DeltaS(theta) values. The Ag(+) adsorption kinetics
      by BMO fit the pseudo-second order model and the apparent activation energy of Ea
      is 21.72 kJ/mol. X-ray photoelectron spectroscopy analysis showed that 15.29%
      Ag(+) adsorbed by BMO was transferred to Ag(0) and meant that redox reaction had
      happened during the adsorption. Desorption using nitric acid and Na2S completely
      recovered the Ag. The results show that BMO produced by strain MnI7-9 has
      potential for bioremediation and reutilization of Ag(+)-containing waste. 

PMID- 24312567
TI  - Altered antibody profiles against common infectious agents in chronic disease.
AB  - Despite the important diagnostic value of evaluating antibody responses to
      individual human pathogens, antibody profiles against multiple infectious agents
      have not been used to explore health and disease mainly for technical reasons. 
      We hypothesized that the interplay between infection and chronic disease might be
      revealed by profiling antibodies against multiple agents. Here, the levels of
      antibodies against a panel of 13 common infectious agents were evaluated with the
      quantitative Luciferase Immunoprecipitation Systems (LIPS) in patients from three
      disease cohorts including those with pathogenic anti-interferon-gamma
      autoantibodies (IFN-gamma AAB), HIV and Sjogren's syndrome (SjS) to determine if
      their antibody profiles differed from control subjects.  The IFN-gamma AAB
      patients compared to controls demonstrated statistically higher levels of
      antibodies against VZV (p=0.0003), EBV (p=0.002), CMV (p=0.003), and C. albicans
      (p=0.03), but lower antibody levels against poliovirus (p=0.04). Comparison of
      HIV patients with blood donor controls revealed that the patients had higher
      levels of antibodies against CMV (p=0.0008), HSV-2 (p=0.0008), EBV (p=0.001), and
      C. albicans (p=0.01), but showed decreased levels of antibodies against
      coxsackievirus B4 (p=0.0008), poliovirus (p=0.0005),   and HHV-6B (p=0.002).
      Lastly, SjS patients had higher levels of anti-EBV antibodies (p=0.03), but lower
      antibody levels against several enteroviruses including a newly identified
      picornavirus, HCoSV-A (p=0.004), coxsackievirus B4 (p=0.04), and poliovirus
      (p=0.02). For the IFN-gamma AAB and HIV cohorts, principal component analysis
      revealed unique antibody clusters that showed the potential to discriminate
      patients from controls.  The results suggest that antibody profiles against these
      and likely other common infectious agents may yield insight into the interplay
      between exposure to infectious agents, dysbiosis, adaptive immunity and disease
      activity. 

PMID- 24312568
TI  - Assessing "dangerous climate change": required reduction of carbon emissions to
      protect young people, future generations and nature.
AB  - We assess climate impacts of global warming using ongoing observations and
      paleoclimate data. We use Earth's measured energy imbalance, paleoclimate data,
      and simple representations of the global carbon cycle and temperature to define
      emission reductions needed to stabilize climate and avoid potentially disastrous
      impacts on today's young people, future generations, and nature. A cumulative
      industrial-era limit of ~500 GtC fossil fuel emissions and 100 GtC storage in the
      biosphere and soil would keep climate close to the Holocene range to which
      humanity and other species are adapted. Cumulative emissions of ~1000 GtC,
      sometimes associated with 2 degrees C global warming, would spur "slow" feedbacks
      and eventual warming of 3-4 degrees C with disastrous consequences. Rapid
      emissions reduction is required to restore Earth's energy balance and avoid ocean
      heat uptake that would practically guarantee irreversible effects. Continuation
      of high fossil fuel emissions, given current knowledge of the consequences, would
      be an act of extraordinary witting intergenerational injustice. Responsible
      policymaking requires a rising price on carbon emissions that would preclude
      emissions from most remaining coal and unconventional fossil fuels and phase down
      emissions from conventional fossil fuels. 

PMID- 24312569
TI  - Real-time fMRI pattern decoding and neurofeedback using FRIEND: an FSL-integrated
      BCI toolbox.
AB  - The demonstration that humans can learn to modulate their own brain activity
      based on feedback of neurophysiological signals opened up exciting opportunities
      for fundamental and applied neuroscience. Although EEG-based neurofeedback has
      been long employed both in experimental and clinical investigation, functional
      MRI (fMRI)-based neurofeedback emerged as a promising method, given its superior
      spatial resolution and ability to gauge deep cortical and subcortical brain
      regions. In combination with improved computational approaches, such as pattern
      recognition analysis (e.g., Support Vector Machines, SVM), fMRI neurofeedback and
      brain decoding represent key innovations in the field of neuromodulation and
      functional plasticity. Expansion in this field and its applications critically
      depend on the existence of freely available, integrated and user-friendly tools
      for the neuroimaging research community. Here, we introduce FRIEND, a graphic
      oriented user-friendly interface package for fMRI neurofeedback and real-time
      multivoxel pattern decoding. The package integrates routines for image
      preprocessing in real-time, ROI-based feedback (single-ROI BOLD level and
      functional connectivity) and brain decoding-based feedback using SVM. FRIEND
      delivers an intuitive graphic interface with flexible processing pipelines
      involving optimized procedures embedding widely validated packages, such as FSL
      and libSVM. In addition, a user-defined visual neurofeedback module allows users
      to easily design and run fMRI neurofeedback experiments using ROI-based or
      multivariate classification approaches. FRIEND is open-source and free for non
      commercial use. Processing tutorials and extensive documentation are available. 

PMID- 24312570
TI  - Measuring the characteristic topography of brain stiffness with magnetic
      resonance elastography.
AB  - PURPOSE: To develop a reliable magnetic resonance elastography (MRE)-based method
      for measuring regional brain stiffness. METHODS: First, simulation studies were
      used to demonstrate how stiffness measurements can be biased by changes in brain
      morphometry, such as those due to atrophy. Adaptive postprocessing methods were
      created that significantly reduce the spatial extent of edge artifacts and
      eliminate atrophy-related bias. Second, a pipeline for regional brain stiffness
      measurement was developed and evaluated for test-retest reliability in 10 healthy
      control subjects. RESULTS: This technique indicates high test-retest
      repeatability with a typical coefficient of variation of less than 1% for global
      brain stiffness and less than 2% for the lobes of the brain and the cerebellum.
      Furthermore, this study reveals that the brain possesses a characteristic
      topography of mechanical properties, and also that lobar stiffness measurements
      tend to correlate with one another within an individual. CONCLUSION: The methods
      presented in this work are resistant to noise- and edge-related biases that are
      common in the field of brain MRE, demonstrate high test-retest reliability, and
      provide independent regional stiffness measurements. This pipeline will allow
      future investigations to measure changes to the brain's mechanical properties and
      how they relate to the characteristic topographies that are typical of many
      neurologic diseases.

PMID- 24312571
TI  - Population dynamics of metastable growth-rate phenotypes.
AB  - Neo-Darwinian evolution has presented a paradigm for population dynamics built on
      random mutations and selection with a clear separation of time-scales between
      single-cell mutation rates and the rate of reproduction. Laboratory experiments
      on evolving populations until now have concentrated on the fixation of beneficial
      mutations. Following the Darwinian paradigm, these experiments probed populations
      at low temporal resolution dictated by the rate of rare mutations, ignoring the
      intermediate evolving phenotypes. Selection however, works on phenotypes rather
      than genotypes. Research in recent years has uncovered the complexity of genotype
      to-phenotype transformation and a wealth of intracellular processes including
      epigenetic inheritance, which operate on a wide range of time-scales. Here, by
      studying the adaptation dynamics of genetically rewired yeast cells, we show a
      novel type of population dynamics in which the intracellular processes intervene
      in shaping the population structure. Under constant environmental conditions, we
      measure a wide distribution of growth rates that coexist in the population for
      very long durations (>100 generations). Remarkably, the fastest growing cells do
      not take over the population on the time-scale dictated by the width of the
      growth-rate distributions and simple selection. Additionally, we measure
      significant fluctuations in the population distribution of various phenotypes:
      the fraction of exponentially-growing cells, the distributions of single-cell
      growth-rates and protein content. The observed fluctuations relax on time-scales
      of many generations and thus do not reflect noisy processes. Rather, our data
      show that the phenotypic state of the cells, including the growth-rate, for large
      populations in a constant environment is metastable and varies on time-scales
      that reflect the importance of long-term intracellular processes in shaping the
      population structure. This lack of time-scale separation between the
      intracellular and population processes calls for a new framework for population
      dynamics which is likely to be significant in a wide range of biological
      contexts, from evolution to cancer. 

PMID- 24312572
TI  - Relationships between values of antibodies to several connective tissue disease
      autoantigens and pulmonary function in a Japanese general population: the
      Takahata study.
AB  - BACKGROUND: Accumulating evidence suggests the involvement of an autoimmune
      mechanism in the pathogenesis of respiratory dysfunction. The aim of this study
      was to investigate the relationship between pulmonary function and serum
      antibodies to several connective tissue disease autoantigens (ACTDA) levels,
      which has not been investigated in a general population. METHODS: Blood sampling
      and spirometry were performed for subjects (n = 3,257) aged >=40 years who
      participated in a community-based annual health check in Takahata, Japan, from
      2004 to 2006. ACTDA was measured by enzyme immunoassay, and subjects with ACTDA
      values >=20 were defined as positive. RESULTS: In males, there were significant
      inverse relationships between logarithmically transformed ACTDA values and
      spirometric parameters, including % predicted values for forced expiratory volume
      in 1 s (FEV1) and maximal midexpiratory flow (MMF) as well as FEV1/forced vital
      capacity (FVC). Multiple linear regression analysis revealed that except for the
      relationship between ACTDA and FEV1/FVC, these relationships were still
      significant after adjustment for Brinkman index (a measure of inhaled cigarette
      consumption). The prevalence of positive ACTDA was greater in male never-smokers
      with mixed ventilation disorders and relatively severe airflow obstruction (%
      predicted FEV1 below the median value). CONCLUSIONS: Autoimmunity may be involved
      in the mechanism of impaired pulmonary function in the general population.

PMID- 24312573
TI  - Meta-modeling of methylprednisolone effects on glucose regulation in rats.
AB  - A retrospective meta-modeling analysis was performed to integrate previously
      reported data of glucocorticoid (GC) effects on glucose regulation following a
      single intramuscular dose (50 mg/kg), single intravenous doses (10, 50 mg/kg),
      and intravenous infusions (0.1, 0.2, 0.3 and 0.4 mg/kg/h) of methylprednisolone
      (MPL) in normal and adrenalectomized (ADX) male Wistar rats. A mechanistic
      pharmacodynamic (PD) model was developed based on the receptor/gene/protein
      mediated GC effects on glucose regulation. Three major target organs (liver,
      white adipose tissue and skeletal muscle) together with some selected
      intermediate controlling factors were designated as important regulators involved
      in the pathogenesis of GC-induced glucose dysregulation. Assessed were dynamic
      changes of food intake and systemic factors (plasma glucose, insulin, free fatty
      acids (FFA) and leptin) and tissue-specific biomarkers (cAMP, phosphoenolpyruvate
      carboxykinase (PEPCK) mRNA and enzyme activity, leptin mRNA, interleukin 6
      receptor type 1 (IL6R1) mRNA and Insulin receptor substrate-1 (IRS-1) mRNA) after
      acute and chronic dosing with MPL along with the GC receptor (GR) dynamics in
      each target organ. Upon binding to GR in liver, MPL dosing caused increased
      glucose production by stimulating hepatic cAMP and PEPCK activity. In adipose
      tissue, the rise in leptin mRNA and plasma leptin caused reduction of food
      intake, the exogenous source of glucose input. Down-regulation of IRS-1 mRNA
      expression in skeletal muscle inhibited the stimulatory effect of insulin on
      glucose utilization further contributing to hyperglycemia. The nuclear drug
      receptor complex served as the driving force for stimulation or inhibition of
      downstream target gene expression within different tissues. Incorporating
      information such as receptor dynamics, as well as the gene and protein induction,
      allowed us to describe the receptor-mediated effects of MPL on glucose regulation
      in each important tissue. This advanced mechanistic model provides unique
      insights into the contributions of major tissues and quantitative hypotheses for
      the multi-factor control of a complex metabolic system. 

PMID- 24312574
TI  - Bimolecular fluorescence complementation; lighting-up tau-tau interaction in
      living cells.
AB  - Abnormal tau aggregation is a pathological hallmark of many neurodegenerative
      disorders and it is becoming apparent that soluble tau aggregates play a key role
      in neurodegeneration and memory impairment. Despite this pathological importance,
      there is currently no single method that allows monitoring soluble tau species in
      living cells. In this regard, we developed a cell-based sensor that visualizes
      tau self-assembly. By introducing bimolecular fluorescence complementation (BiFC)
      technique to tau, we were able to achieve spatial and temporal resolution of tau
      tau interactions in a range of states, from soluble dimers to large aggregates.
      Under basal conditions, tau-BiFC cells exhibited little fluorescence intensity,
      implying that the majority of tau molecules exist as monomers. Upon chemically
      induced tau hyperphosphorylation, BiFC fluorescence greatly increased, indicating
      an increased level of tau-tau interactions. As an indicator of tau assembly, our
      BiFC sensor would be a useful tool for investigating tau pathology. 

PMID- 24312575
TI  - Increased B cell and cytotoxic NK cell proportions and increased T cell
      responsiveness in blood of natalizumab-treated multiple sclerosis patients.
AB  - BACKGROUND: Changes in the blood lymphocyte composition probably both mediate and
      reflect the effects of natalizumab treatment in multiple sclerosis, with
      implications for treatment benefits and risks. METHODS: A broad panel of markers
      for lymphocyte populations, including states of activation and co-stimulation, as
      well as functional T cell responses to recall antigens and mitogens, were
      assessed by flow cytometry in 40 patients with relapsing multiple sclerosis
      before and after one-year natalizumab treatment. RESULTS: Absolute numbers of all
      major lymphocyte populations increased after treatment, most markedly for NK and
      B cells. The fraction of both memory and presumed regulatory B cell subsets
      increased, as did CD3(-)CD56(dim) cytotoxic NK cells, whereas CD3(-)CD56(bright)
      regulatory NK cells decreased. The increase in cell numbers was further
      associated with a restored T cell responsiveness to recall antigens and mitogens
      in functional assays. CONCLUSIONS: Our data confirms that natalizumab treatment
      increases the number of lymphocytes in blood, likely mirroring the expression of
      VLA-4 being highest on NK and B cells. This finding supports reduction of
      lymphocyte extravasation as a main mode of action, although the differential
      effects on subpopulation composition suggests that cell-signalling may also be
      affected. The systemic increase in T cell responsiveness reflects the increase in
      numbers, and while augmenting anti-infectious responses systemically, localized
      responses may become correspondingly decreased.

PMID- 24312576
TI  - Demographic histories, isolation and social factors as determinants of the
      genetic structure of Alpine linguistic groups.
AB  - Great European mountain ranges have acted as barriers to gene flow for resident
      populations since prehistory and have offered a place for the settlement of
      small, and sometimes culturally diverse, communities. Therefore, the human groups
      that have settled in these areas are worth exploring as an important potential
      source of diversity in the genetic structure of European populations. In this
      study, we present new high resolution data concerning Y chromosomal variation in
      three distinct Alpine ethno-linguistic groups, Italian, Ladin and German.
      Combining unpublished and literature data on Y chromosome and mitochondrial
      variation, we were able to detect different genetic patterns. In fact, within and
      among population diversity values observed vary across linguistic groups, with
      German and Italian speakers at the two extremes, and seem to reflect their
      different demographic histories. Using simulations we inferred that the joint
      effect of continued genetic isolation and reduced founding group size may explain
      the apportionment of genetic diversity observed in all groups. Extending the
      analysis to other continental populations, we observed that the genetic
      differentiation of Ladins and German speakers from Europeans is comparable or
      even greater to that observed for well known outliers like Sardinian and Basques.
      Finally, we found that in south Tyroleans, the social practice of Geschlossener
      Hof, a hereditary norm which might have favored male dispersal, coincides with a
      significant intra-group diversity for mtDNA but not for Y chromosome, a genetic
      pattern which is opposite to those expected among patrilocal populations.
      Together with previous evidence regarding the possible effects of "local
      ethnicity" on the genetic structure of German speakers that have settled in the
      eastern Italian Alps, this finding suggests that taking socio-cultural factors
      into account together with geographical variables and linguistic diversity may
      help unveil some yet to be understood aspects of the genetic structure of
      European populations. 

PMID- 24312577
TI  - GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile
      duct.
AB  - Intraductal papillary neoplasms of the bile duct (IPNB) shows favorable prognosis
      and is regarded as a biliary counterpart of intraductal papillary mucinous
      neoplasm (IPMN) of the pancreas. Although activating point mutations of GNAS at
      codon 201 have been detected in approximately two thirds of IPMNs of the
      pancreas, there have been few studies on GNAS mutations in IPNBs. This study
      investigates the status of GNAS and KRAS mutations and their association with
      clinicopathological factors in IPNBs. We examined the status of GNAS mutation at
      codon 201 and KRAS mutation at codon 12&13, degree of mucin production and
      immunohistochemical expressions of MUC mucin core proteins in 29 patients (M/F =
      15/14) with IPNB in intrahepatic and perihilar bile ducts (perihilar IPNB) and 6
      patients (M/F = 5/1) with IPNB in distal bile ducts (distal IPNB). GNAS mutations
      and KRAS mutations were detected in 50% and 46.2% of IPNBs, respectively. There
      was no significant correlation between the status of GNAS mutation and
      clinicopathological factors in IPNBs, whereas, the status of KRAS mutation was
      significantly inversely correlated with the degree of MUC2 expression in IPNBs
      (p<0.05). All IPNBs with GNAS mutation only showed high-mucin production. Degree
      of mucin production was significantly higher in perihilar IPNBs than distal IPNBs
      (p<0.05). MUC2 and MUC5AC expression was significantly higher in IPNBs with high
      mucin production than those with low-mucin production (p<0.01 and p<0.05,
      respectively). In conclusions, this study firstly disclosed frequent GNAS
      mutations in IPNBs, similarly to IPMNs. This may suggest a common
      histopathogenesis of IPNBs and IPMNs. The status of KRAS mutations was inversely
      correlated to MUC2 expression and this may suggest heterogeneous properties of
      IPNBs. IPNBs with high-mucin production are characterized by perihilar location
      and high expression of MUC2 and MUC5AC, irrespective of the status of GNAS and
      KRAS mutations. 

PMID- 24312578
TI  - Discovery of a mammalian splice variant of myostatin that stimulates myogenesis.
AB  - Myostatin plays a fundamental role in regulating the size of skeletal muscles. To
      date, only a single myostatin gene and no splice variants have been identified in
      mammals. Here we describe the splicing of a cryptic intron that removes the
      coding sequence for the receptor binding moiety of sheep myostatin. The deduced
      polypeptide sequence of the myostatin splice variant (MSV) contains a 256 amino
      acid N-terminal domain, which is common to myostatin, and a unique C-terminus of
      65 amino acids. Western immunoblotting demonstrated that MSV mRNA is translated
      into protein, which is present in skeletal muscles. To determine the biological
      role of MSV, we developed an MSV over-expressing C2C12 myoblast line and showed
      that it proliferated faster than that of the control line in association with an
      increased abundance of the CDK2/Cyclin E complex in the nucleus. Recombinant
      protein made for the novel C-terminus of MSV also stimulated myoblast
      proliferation and bound to myostatin with high affinity as determined by surface
      plasmon resonance assay. Therefore, we postulated that MSV functions as a binding
      protein and antagonist of myostatin. Consistent with our postulate, myostatin
      protein was co-immunoprecipitated from skeletal muscle extracts with an MSV
      specific antibody. MSV over-expression in C2C12 myoblasts blocked myostatin
      induced Smad2/3-dependent signaling, thereby confirming that MSV antagonizes the
      canonical myostatin pathway. Furthermore, MSV over-expression increased the
      abundance of MyoD, Myogenin and MRF4 proteins (P<0.05), which indicates that MSV
      stimulates myogenesis through the induction of myogenic regulatory factors. To
      help elucidate a possible role in vivo, we observed that MSV protein was more
      abundant during early post-natal muscle development, while myostatin remained
      unchanged, which suggests that MSV may promote the growth of skeletal muscles. We
      conclude that MSV represents a unique example of intra-genic regulation in which
      a splice variant directly antagonizes the biological activity of the canonical
      gene product. 

PMID- 24312580
TI  - Cloning and analysis of a large plasmid pBMB165 from Bacillus thuringiensis
      revealed a novel plasmid organization.
AB  - In this study, we report a rapid cloning strategy for large native plasmids via a
      contig linkage map by BAC libraries. Using this method, we cloned a large plasmid
      pBMB165 from Bacillus thuringiensis serovar tenebrionis strain YBT-1765. Complete
      sequencing showed that pBMB165 is 77,627 bp long with a GC-content of 35.36%, and
      contains 103 open reading frames (ORFs). Sequence analysis and comparison reveals
      that pBMB165 represents a novel plasmid organization: it mainly consists of a
      pXO2-like replicon and mobile genetic elements (an inducible prophage BMBTP3 and
      a set of transposable elements). This is the first description of this plasmid
      organization pattern, which may result from recombination events among the
      plasmid replicon, prophage and transposable elements. This plasmid organization
      reveals that the prophage BMBTP3 may use the plasmid replicon to maintain its
      genetic stability. Our results provide a new approach to understanding co
      evolution between bacterial plasmids and bacteriophage. 

PMID- 24312579
TI  - Reinvestigation of aminoacyl-tRNA synthetase core complex by affinity
      purification-mass spectrometry reveals TARSL2 as a potential member of the
      complex.
AB  - Twenty different aminoacyl-tRNA synthetases (ARSs) link each amino acid to their
      cognate tRNAs. Individual ARSs are also associated with various non-canonical
      activities involved in neuronal diseases, cancer and autoimmune diseases. Among
      them, eight ARSs (D, EP, I, K, L, M, Q and RARS), together with three ARS
      interacting multifunctional proteins (AIMPs), are currently known to assemble the
      multi-synthetase complex (MSC). However, the cellular function and global
      topology of MSC remain unclear. In order to understand the complex interaction
      within MSC, we conducted affinity purification-mass spectrometry (AP-MS) using
      each of AIMP1, AIMP2 and KARS as a bait protein. Mass spectrometric data were
      funneled into SAINT software to distinguish true interactions from background
      contaminants. A total of 40, 134, 101 proteins in each bait scored over 0.9 of
      SAINT probability in HEK 293T cells. Complex-forming ARSs, such as DARS, EPRS,
      IARS, Kars, LARS, MARS, QARS and RARS, were constantly found to interact with
      each bait. Variants such as, AIMP2-DX2 and AIMP1 isoform 2 were found with
      specific peptides in KARS precipitates. Relative enrichment analysis of the mass
      spectrometric data demonstrated that TARSL2 (threonyl-tRNA synthetase like-2) was
      highly enriched with the ARS-core complex. The interaction was further confirmed
      by coimmunoprecipitation of TARSL2 with other ARS core-complex components. We
      suggest TARSL2 as a new component of ARS core-complex. 

PMID- 24312581
TI  - Local administration of AAV-BDNF to subventricular zone induces functional
      recovery in stroke rats.
AB  - Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ)
      plays an important role in neurorepair after injury. Previous studies have shown
      that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from
      SVZ explants in neonatal mice in vitro. The purpose of this study was to identify
      the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF
      protein production after AAV-BDNF infection was verified in primary neuronal
      culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats
      at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues
      were collected from the brain and placed in Metrigel cultures 1 day after MCAo.
      Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the
      stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with
      AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local
      administration of AAV-BDNF significantly enhanced recovery of locomotor function
      and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere
      in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ
      increases behavioral recovery post stroke, possibly through the enhancement of
      migration of cells from SVZ in stroke animals. Regional manipulation of BDNF
      expression through AAV may be a novel approach for neurorepair in stroke brains. 

PMID- 24312582
TI  - Post-mastectomy radiotherapy for breast cancer patients with t1-t2 and 1-3
      positive lymph nodes: a meta-analysis.
AB  - BACKGROUND: The role of post-mastectomy radiotherapy (PMRT) in patients with T1-2
      and 1-3 positive lymph nodes remains controversial. The aim of this study is to
      investigate the possible benefits of PMRT for this subgroup. METHODS: Three
      electronic databases were systematically quarried (Cochrane Library, MEDLINE, and
      EMBASE) for published studies evaluating the effects of PMRT on breast cancer
      patients with T1-T2 tumors with 1-3 positive lymph nodes. Of the 334 studies
      identified, information was available for 3432 patients from 10 clinical studies.
      Pooled relative risk estimates (RR) and overall survival (OS) were calculated
      using the inverse variance weighted approach, publication bias and chi-square
      test were also calculated. RESULTS: From the 10 studies, the pooled RR (RRs) for
      locoregional recurrence (LRR) with PMRT was 0.348 (95% CI = 0.254 to 0.477),
      suggesting a significant benefit for PMRT to decrease the risk of LRR in patients
      with T1-T2 tumors and 1-3 positive nodes (p<0.05). Reporting bias ( Begg's p =
      0.152; Egger's p = 0.107) or significant heterogeneity (Cochran's p = 0.380; I(2)
      = 6.7%) were not detected. For further subset analysis, the RR for T1, N1-3+
      tumors was 0.330 (95% CI = 0.171 to 0.639); for T2, N1-3+ tumors the RR was 0.226
      (95% CI = 0.121 to 0.424). The pooled RR for overall survival (OS) was not
      significantly different between PMRT and no-PMRT group (1.051, 95% CI =1.001 to
      1.104). CONCLUSIONS: Our pooled analysis revealed that PMRT significantly reduces
      the risk of LRR in patients with TI-T2 tumors with 1-3 positive nodes, and the
      magnitude of the LRR risk reduction is slightly greater for larger tumors. Our
      results suggest that PMRT should be considered for patients with T1/T2 tumors
      with 1-3 positive nodes to decrease the relatively high risk of LRR.

PMID- 24312583
TI  - Candidate gene identification for systemic lupus erythematosus using network
      centrality measures and gene ontology.
AB  - Systemic lupus erythematosus (SLE) commonly accredited as "the great imitator" is
      a highly complex disease involving multiple gene susceptibility with non-specific
      symptoms. Many experimental and computational approaches have been used to
      investigate the disease related candidate genes. But the limited knowledge of
      gene function and disease correlation and also lack of complete functional
      details about the majority of genes in susceptible locus, encumbrances the
      identification of SLE related candidate genes. In this paper, we have studied the
      human immunome network (undirected) using various graph theoretical centrality
      measures integrated with the gene ontology terms to predict the new candidate
      genes. As a result, we have identified 8 candidate genes, which may act as
      potential targets for SLE disease. We have also carried out the same analysis by
      replacing the human immunome network with human immunome signaling network
      (directed) and as an outcome we have obtained 5 candidate genes as potential
      targets for SLE disease. From the comparison study, we have found these two
      approaches are complementary in nature. 

PMID- 24312584
TI  - Insecurities of women regarding breast cancer research: a qualitative study.
AB  - OBJECTIVES: Only 1.2%-11% of all potential study participants participate in
      cancer studies. Low participation rates can result in bias or in a failure to
      obtain data saturation. Subject-scientific psychology assumes that reasons for
      acting are based on individual premises. The objective of this study was to
      render reproducible individual reasons of female breast cancer patients to
      participate or not participate in breast cancer studies using a qualitative
      approach. METHODS: Problem-based interviews were conducted with female breast
      cancer patients. The selection of interview partners continued until theoretical
      data saturation was achieved. RESULTS: As main arguments against participation
      emotional overload and too many medication side-effects were stated. Improvement
      of health-related values, long-term protection and comprehensive follow-up exams
      were stated as arguments for participation. Trust in the attending physician was
      mentioned as influencing both participation and non-participation. CONCLUSIONS: A
      significant influential factor determining willingness to participate in studies
      was one's contentment with patient-physician communication. In order to guarantee
      an adequate patient decision-making process, keeping existing standards for
      patient briefings is absolutely mandatory.

PMID- 24312585
TI  - Lyoniresinol 3alpha-O-beta-D-glucopyranoside-mediated hypoglycaemia and its
      influence on apoptosis-regulatory protein expression in the injured kidneys of
      streptozotocin-induced mice.
AB  - Averrhoa carambola L. (Oxalidaceae) root (ACLR) has a long history of use in
      traditional Chinese medicine for treating diabetes and diabetic nephropathy (DN).
      (+/-)-Lyoniresinol 3alpha-O-beta-D-glucopyranoside (LGP1, LGP2) were two chiral
      lignan glucosides that were isolated from the ACLR. The purpose of this study was
      to investigate the effect of LGP1 and LGP2-mediated hypoglycaemia on renal injury
      in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were
      administrated LGP1 and LGP2 orally (20, 40, 80 mg/kg body weight/d) for 14 days.
      Hyperglycaemia and the expression of related proteins such as nuclear factor
      kappaB (NF-kappaB), caspase-3, -8, -9, and Bcl-associated X protein (Bax) were
      markedly decreased by LGP1 treatment. However, LGP2 treatment had no
      hypoglycaemic activity. Diabetes-dependent alterations in the kidney such as
      glomerular hypertrophy, excessive extracellular matrix amassing, and glomerular
      and tubular basement membrane thickening were improved after 14 days of LGP1
      treatment. B cell lymphoma Leukaemia-2 (Bcl-2) expression was reduced in the STZ
      induced diabetic mouse kidneys but was enhanced by LGP1 treatment. These findings
      suggest that LGP1 treatment may inhibit diabetic nephropathy progression and may
      regulate several pharmacological targets for treating or preventing diabetic
      nephropathy. 

PMID- 24312586
TI  - Early increase and late decrease of purkinje cell dendritic spine density in
      prion-infected organotypic mouse cerebellar cultures.
AB  - Prion diseases are infectious neurodegenerative diseases associated with the
      accumulation of protease-resistant prion protein, neuronal loss, spongiform
      change and astrogliosis. In the mouse model, the loss of dendritic spines is one
      of the earliest pathological changes observed in vivo, occurring 4-5 weeks after
      the first detection of protease-resistant prion protein in the brain. While there
      are cell culture models of prion infection, most do not recapitulate the
      neuropathology seen in vivo. Only the recently developed prion organotypic slice
      culture assay has been reported to undergo neuronal loss and the development of
      some aspects of prion pathology, namely small vacuolar degeneration and
      tubulovesicular bodies. Given the rapid replication of prions in this system,
      with protease-resistant prion protein detectable by 21 days, we investigated
      whether the dendritic spine loss and altered dendritic morphology seen in prion
      disease might also develop within the lifetime of this culture system. Indeed,
      six weeks after first detection of protease-resistant prion protein in tga20
      mouse cerebellar slice cultures infected with RML prion strain, we found a
      statistically significant loss of Purkinje cell dendritic spines and altered
      dendritic morphology in infected cultures, analogous to that seen in vivo. In
      addition, we found a transient but statistically significant increase in Purkinje
      cell dendritic spine density during infection, at the time when protease
      resistant prion protein was first detectable in culture. Our findings support the
      use of this slice culture system as one which recapitulates prion disease
      pathology and one which may facilitate study of the earliest stages of prion
      disease pathogenesis. 

PMID- 24312587
TI  - Relationships between HDL-C, hs-CRP, with central arterial stiffness in
      apparently healthy people undergoing a general health examination.
AB  - BACKGROUND: Some cardiovascular risk factors have been confirmed to be positively
      correlated with arterial stiffness. However, it is unclear whether HDL-C, a well
      established anti-risk factor, has an independent association with arterial
      stiffness. The aim of this study was to evaluate the relationship between HDL-C
      levels and arterial stiffness and the possible role of high-sensitivity C
      reactive protein (hs-CRP) in this potential correlation in apparently healthy
      adults undergoing a general health examination in China. MATERIALS AND METHODS:
      This was a cross-sectional survey. In total, 15,302 participants (age range, 18
      82 years; mean, 43.88+/-8.44 years) were recruited during routine health status
      examinations. A questionnaire was used and we measured the body mass index,
      systolic and diastolic blood pressure, and fasting glucose, and serum lipid, uric
      acid, hs-CRP, and serum creatinine levels of each participant. Central arterial
      stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV). RESULTS:
      HDL-C levels decreased as cf-PWV increased. Pearson's correlation analysis
      revealed that HDL-C levels were associated with cf-PWV (r=-0.18, P<0.001). hs-CRP
      levels were positively associated with cf-PWV (r=0.13). After adjustment for all
      confounders, HDL-C was inversely independently associated with all quartiles of
      cf-PWV. Furthermore, HDL-C was associated with cf-PWV in different quartiles of
      hs-CRP, and the correlation coefficients (r) gradually decreased with increasing
      hs-CRP levels (quartiles 1-4). CONCLUSIONS: HDL-C is inversely independently
      associated with central arterial stiffness. The anti-inflammatory activity of HDL
      C may mediate its relationship with cf-PWV. Further, long-term follow-up studies
      are needed to evaluate whether high HDL-C levels are protective against central
      artery stiffening through the anti-inflammatory activity of HDL-C.

PMID- 24312588
TI  - Potential use of hyperoxygenated solution as a treatment strategy for carbon
      monoxide poisoning.
AB  - AIM: Carbon monoxide (CO) poisoning can cause permanent damage in tissues that
      are sensitive to hypoxia. We explored the feasibility and efficacy of using a
      hyperoxygenated solution (HOS) to treat severe acute CO poisoning in an animal
      model. METHODS: Male Sprague-Dawley rats were subjected to CO poisoning. The HOS
      was administered into the femoral vein of these rats through a catheter (10
      ml/kg). Carboxyhemoglobin (COHb) and blood gases were used to assess the early
      damage caused by CO poisoning. S100beta was measured to predict the development
      of late cognitive sequelae of CO. The Morris water maze test was performed to
      assess cognitive function, and Nissl staining was performed to observe histologic
      change. RESULTS: The COHb concentrations rapidly decreased at 5 min after the HOS
      administration; however, the PaO2 and SaO2 in rats treated with HOS increased
      significantly 5 min after the HOS administration. The S100beta concentrations,
      which increased significantly after CO poisoning, increased at a much slower rate
      in the rats treated with HOS (HOS group) compared with the rats treated with O2
      inhalation (O2 group). The escape latency in the place navigation test was
      shortened after CO poisoning on days 11-15 and days 26-30, and the swimming time
      in quadrant 4 in the spatial probe test on days 15 and 30 after CO poisoning was
      prolonged in the rats treated with HOS injection compared with the rats treated
      with oxygen inhalation or normal saline injection. The neuronal degeneration in
      the HOS group was alleviated than that in the CO or O2 group. CONCLUSION: HOS
      efficiently alleviates the brain damage in acute CO-poisoned rats and thus may
      serve as a new way to treat human patients with CO poisoning in clinical
      practice.

PMID- 24312589
TI  - The association of socioeconomic status and access to low-volume service
      providers in breast cancer.
AB  - BACKGROUND: No large-scale study has explored the combined effect of patients'
      individual and neighborhood socioeconomic status (SES) on their access to a low
      volume provider for breast cancer surgery. The purpose of this study was to
      explore under a nationwide universal health insurance system whether breast
      cancer patients from a lower individual and neighborhood SES are
      disproportionately receiving breast cancer surgery from low-volume providers.
      METHODS: 5,750 patients who underwent breast cancer surgery in 2006 were
      identified from the Taiwan National Health Insurance Research Database. The Cox
      proportional hazards model was used to compare the access to a low-volume
      provider between the different individual and neighborhood SES groups after
      adjusting for possible confounding and risk factors. Hosmer-Lemeshow goodness-of
      fit statistic was used to determine how well the model fit the data. RESULTS:
      Univariate analysis data shows that patients in disadvantaged neighborhood were
      more likely to receive breast cancer surgery at low-volume hospitals; and lower
      SES patients were more likely to receive surgery from low-volume surgeons. In
      multivariate analysis, after adjusting for patient characteristics, the odds
      ratios of moderate- and low-SES patients in disadvantaged neighborhood receiving
      surgery at low-volume hospitals was 1.47 (95% confidence interval=1.19-1.81) and
      1.31 (95% confidence interval=1.05-1.64) respectively compared with high-SES
      patients in advantaged neighborhood. Moderate- and low-SES patients from either
      advantaged or disadvantaged neighborhood had an odds ratios ranging from 1.51 to
      1.80 (p<0.001) to receiving surgery from low-volume surgeons. In Hosmer-Lemeshow
      goodness-of-fit test, p>0.05 that shows the model has a good fit. CONCLUSIONS: In
      this population-based cross-sectional study, even under a nationwide universal
      health insurance system, disparities in access to healthcare existed. Breast
      cancer patients from a lower individual and neighborhood SES are more likely to
      receive breast cancer surgery from low-volume providers. The authorities and
      public health policies should keep focusing on these vulnerable groups.

PMID- 24312590
TI  - Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with
      neurological disorders: a systematic review and meta-analysis.
AB  - BACKGROUND: Modafinil is a novel wake-promoting agent approved by the FDA
      ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy,
      shift work sleep disorder and obstructive sleep apnea. Existing trials of
      modafinil for fatigue and EDS associated with neurological disorders provided
      inconsistent results. This meta-analysis was aimed to assess drug safety and
      effects of modafinil on fatigue and EDS associated with neurological disorders.
      METHODS: A comprehensive literature review was conducted in order to identify
      published studies assessing the effects of modafinil on fatigue and EDS
      associated with neurological disorders. Primary outcomes included fatigue and
      EDS. Secondary outcomes included depression and adverse effects. FINDINGS: Ten
      randomized controlled trials were identified including 4 studies of Parkinson's
      disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and
      1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our
      results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82
      95% CI -1.54 - -0.11 p=0.02, I(2)=0%), while a beneficial effect of modafinil on
      fatigue was not confirmed in the pooled studies of PD or MS. Treatment results
      demonstrated a clear beneficial effect of modafinil on EDS in patients with PD
      (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I(2)=14%), but not with MS and TBI. No
      difference was seen between modafinil and placebo treatments in patients with
      PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events
      were similar between modafinil and placebo groups except that more patients were
      found with insomnia and nausea in modafinil group. CONCLUSIONS: Existing trials
      of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided
      inconsistent results. The majority of the studies had small sample sizes.
      Modafinil is not yet sufficient to be recommended for these medical conditions
      until solid data are available.

PMID- 24312591
TI  - Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) and integrins are adhesion molecules
      that play critical roles in host defense and innate immunity. PSGL-1 mediates
      leukocyte rolling and primes leukocytes for integrin-mediated adhesion. However,
      the mechanism that PSGL-1 as a rolling receptor in regulating integrin activation
      has not been well characterized. Here, we investigate the function of lipid raft
      in regulating PSGL-1 induced beta2 integrin-mediated HL-60 cells adhesion. PSGL-1
      ligation with antibody enhances the beta2 integrin activation and beta2 integrin
      dependent adhesion to ICAM-1. Importantly, with the treatment of methyl-beta
      cyclodextrin (MbetaCD), we confirm the role of lipid raft in regulating the
      activation of beta2 integrin. Furthermore, we find that the protein level of PSGL
      1 decreased in raft fractions in MbetaCD treated cells. PSGL-1 ligation induces
      the recruitment of spleen tyrosine kinase (Syk), a tyrosine kinase and Vav1 (the
      pivotal downstream effector of Syk signaling pathway involved in cytoskeleton
      regulation) to lipid raft. Inhibition of Syk activity with pharmacologic
      inhibitor strongly reduces HL-60 cells adhesion, implicating Syk is crucial for
      PSGL-1 mediated beta2 integrin activation. Taken together, we report that
      ligation of PSGL-1 on HL-60 cells activates beta2 integrin, for which lipid raft
      integrity and Syk activation are responsible. These findings have shed new light
      on the mechanisms that connect leukocyte initial rolling with subsequent
      adhesion. 

PMID- 24312592
TI  - Polarized regulation of glycogen synthase kinase-3beta is important for glioma
      cell invasion.
AB  - Glioma malignancy greatly depends on its aggressive invasion. The establishment
      of cell polarity is an important initial step for cell migration, which is
      essential for cell-directional translocation. However, our understanding of the
      molecular mechanisms underlying cell polarity formation in glioma cell invasion
      remains limited. Glycogen synthase kinase-3 (GSK-3) has a critical role in the
      formation of cell polarity. We therefore investigated whether localized GSK
      3beta, a subtype of GSK-3, is important for glioma cell invasion. We reported
      here that the localized phosphorylation of GSK-3beta at the Ser9 (pSer9-GSK
      3beta) was critical for glioma cell invasion. Scratching glioma cell monolayer up
      regulated pSer9-GSK-3beta specifically at the wound edge. Inhibition of GSK-3
      impaired the cell polarity and reduced the directional persistence of cell
      migration. Consistently, down-regulation of GSK-3alpha and 3beta by specific
      small interfering RNAs inhibited glioma cell invasion. Over-expressing wild-type
      or constitutively active forms of GSK-3beta also inhibited the cell invasion.
      These results indicated the polarized localization of GSK-3 regulation in cell
      migration might be also important for glioma cell migration. Further, EGF
      regulated both GSK-3alpha and 3beta, but only pSer9-GSK-3beta was enriched at the
      leading edge of scratched glioma cells. Up- or down-regulation of GSK-3beta
      inhibited EGF-stimulated cell invasion. Moreover, EGF specifically regulated GSK
      3beta, but not GSK-3alpha, through atypical PKC pathways. Our results indicated
      that GSK-3 was important for glioma cell invasion and localized inhibition of GSK
      3beta was critical for cell polarity formation. 

PMID- 24312593
TI  - Down-regulation of OsSPX1 causes high sensitivity to cold and oxidative stresses
      in rice seedlings.
AB  - Rice SPX domain gene, OsSPX1, plays an important role in the phosphate (Pi)
      signaling network. Our previous work showed that constitutive overexpression of
      OsSPX1 in tobacco and Arabidopsis plants improved cold tolerance while also
      decreasing total leaf Pi. In the present study, we generated rice antisense and
      sense transgenic lines of OsSPX1 and found that down-regulation of OsSPX1 caused
      high sensitivity to cold and oxidative stresses in rice seedlings. Compared to
      wild-type and OsSPX1-sense transgenic lines, more hydrogen peroxide accumulated
      in seedling leaves of OsSPX1-antisense transgenic lines for controls, cold and
      methyl viologen (MV) treatments. Glutathione as a ROS scavenger could protect the
      antisense transgenic lines from cold and MV stress. Rice whole genome GeneChip
      analysis showed that some oxidative-stress marker genes (e.g. glutathione S
      transferase and P450s) and Pi-signaling pathway related genes (e.g. OsPHO2) were
      significantly down-regulated by the antisense of OsSPX1. The microarray results
      were validated by real-time RT-PCR. Our study indicated that OsSPX1 may be
      involved in cross-talks between oxidative stress, cold stress and phosphate
      homeostasis in rice seedling leaves. 

PMID- 24312594
TI  - Human omental-derived adipose stem cells increase ovarian cancer proliferation,
      migration, and chemoresistance.
AB  - OBJECTIVES: Adipose tissue contains a population of multipotent adipose stem
      cells (ASCs) that form tumor stroma and can promote tumor progression. Given the
      high rate of ovarian cancer metastasis to the omental adipose, we hypothesized
      that omental-derived ASC may contribute to ovarian cancer growth and
      dissemination. MATERIALS AND METHODS: We isolated ASCs from the omentum of three
      patients with ovarian cancer, with (O-ASC4, O-ASC5) and without (O-ASC1) omental
      metastasis. BM-MSCs, SQ-ASCs, O-ASCs were characterized with gene expression
      arrays and metabolic analysis. Stromal cells effects on ovarian cancer cells
      proliferation, chemoresistance and radiation resistance was evaluated using co
      culture assays with luciferase-labeled human ovarian cancer cell lines. Transwell
      migration assays were performed with conditioned media from O-ASCs and control
      cell lines. SKOV3 cells were intraperitionally injected with or without O-ASC1 to
      track in-vivo engraftment. RESULTS: O-ASCs significantly promoted in vitro
      proliferation, migration chemotherapy and radiation response of ovarian cancer
      cell lines. O-ASC4 had more marked effects on migration and chemotherapy response
      on OVCA 429 and OVCA 433 cells than O-ASC1. Analysis of microarray data revealed
      that O-ASC4 and O-ASC5 have similar gene expression profiles, in contrast to O
      ASC1, which was more similar to BM-MSCs and subcutaneous ASCs in hierarchical
      clustering. Human O-ASCs were detected in the stroma of human ovarian cancer
      murine xenografts but not uninvolved ovaries. CONCLUSIONS: ASCs derived from the
      human omentum can promote ovarian cancer proliferation, migration,
      chemoresistance and radiation resistance in-vitro. Furthermore, clinical O-ASCs
      isolates demonstrate heterogenous effects on ovarian cancer in-vitro.

PMID- 24312595
TI  - Leaf longevity as a normalization constant in allometric predictions of plant
      production.
AB  - In metabolic scaling theory the size-dependence of plant processes is described
      by a power function of form Y=Y o M (theta) where Y is a characteristic such as
      plant productivity that changes with plant size (M) raised to the theta (th)
      power and Y o is a normalization constant that adjusts the general relationship
      across environments and species. In essence, the theory considers that the value
      of theta arises in the size-dependent relationship between leaf area and vascular
      architecture that influences plant function and that Y o modulates this general
      relationship to account for ecological and evolutionary effects on the exchange
      of resources between plant and environment. Enquist and colleagues have shown
      from first principles that Y o is a function of carbon use efficiency, the carbon
      fraction of a plant, the area-specific carbon assimilation rate of a leaf, the
      laminar area of a leaf, and the mass of a leaf. We show that leaf longevity
      provides a functional integration of these traits that can serve as a simpler
      normalization in scaling plant productivity for individual species and
      potentially for mixed-species communities as well. 

PMID- 24312596
TI  - Expectation modulates the effect of deep brain stimulation on motor and cognitive
      function in tremor-dominant Parkinson's disease.
AB  - Expectation contributes to placebo and nocebo responses in Parkinson's disease
      (PD). While there is evidence for expectation-induced modulations of
      bradykinesia, little is known about the impact of expectation on resting tremor.
      Subthalamic nucleus (STN) deep brain stimulation (DBS) improves cardinal PD motor
      symptoms including tremor whereas impairment of verbal fluency (VF) has been
      observed as a potential side-effect. Here we investigated how expectation
      modulates the effect of STN-DBS on resting tremor and its interaction with VF. In
      a within-subject-design, expectation of 24 tremor-dominant PD patients regarding
      the impact of STN-DBS on motor symptoms was manipulated by verbal suggestions
      (positive [placebo], negative [nocebo], neutral [control]). Patients participated
      with (MedON) and without (MedOFF) antiparkinsonian medication. Resting tremor was
      recorded by accelerometry and bradykinesia of finger tapping and diadochokinesia
      were assessed by a 3D ultrasound motion detection system. VF was quantified by
      lexical and semantic tests. In a subgroup of patients, the effect of STN-DBS on
      tremor was modulated by expectation, i.e. tremor decreased (placebo response) or
      increased (nocebo response) by at least 10% as compared to the control condition
      while no significant effect was observed for the overall group. Interestingly,
      nocebo responders in MedON were additionally characterized by significant
      impairment in semantic verbal fluency. In contrast, bradykinesia was not affected
      by expectation. These results indicate that the therapeutic effect of STN-DBS on
      tremor can be modulated by expectation in a subgroup of patients and suggests
      that tremor is also among the parkinsonian symptoms responsive to placebo and
      nocebo interventions. While positive expectations enhanced the effect of STN-DBS
      by further decreasing the magnitude of tremor, negative expectations counteracted
      the therapeutic effect and at the same time exacerbated a side-effect often
      associated with STN-DBS. The present findings underscore the potency of patients'
      expectation and its relevance for therapeutic outcomes. 

PMID- 24312597
TI  - Peroxide responsive regulator PerR of group A Streptococcus is required for the
      expression of phage-associated DNase Sda1 under oxidative stress.
AB  - The peroxide regulator (PerR) is a ferric uptake repressor-like protein, which is
      involved in adaptation to oxidative stress and iron homeostasis in group A
      streptococcus. A perR mutant is attenuated in surviving in human blood,
      colonization of the pharynx, and resistance to phagocytic clearance, indicating
      that the PerR regulon affects both host environment adaptation and immune escape.
      Sda1 is a phage-associated DNase which promotes M1T1 group A streptococcus
      escaping from phagocytic cells by degrading DNA-based neutrophil extracellular
      traps. In the present study, we found that the expression of sda1 is up-regulated
      under oxidative conditions in the wild-type strain but not in the perR mutant. A
      gel mobility shift assay showed that the recombinant PerR protein binds the sda1
      promoter. In addition, mutation of the conserved histidine residue in the metal
      binding site of PerR abolished sda1 expression under hydrogen peroxide treatment
      conditions, suggesting that PerR is directly responsible for the sda1 expression
      under oxidative stress. Our results reveal PerR-dependent sda1 expression under
      oxidative stress, which may aid innate immune escape of group A streptococcus. 

PMID- 24312598
TI  - Identification of CHIP as a novel causative gene for autosomal recessive
      cerebellar ataxia.
AB  - Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders
      that are characterized by complex clinical and genetic heterogeneity. Although
      more than 20 disease-causing genes have been identified, many patients are still
      currently without a molecular diagnosis. In a two-generation autosomal recessive
      cerebellar ataxia family, we mapped a linkage to a minimal candidate region on
      chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850
      and rs1218762. By combining the defined linkage region with the whole-exome
      sequencing results, we identified a homozygous mutation (c.493CT) in CHIP
      (NM_005861) in this family. Using Sanger sequencing, we also identified two
      compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene
      in two additional kindreds. These mutations co-segregated exactly with the
      disease in these families and were not observed in 500 control subjects with
      matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D
      aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and
      cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the
      degradation of NR2A, which may underlie the pathogenesis of ataxia. In
      conclusion, using a combination of whole-exome sequencing and linkage analysis,
      we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel
      causative gene for autosomal recessive cerebellar ataxia. 

PMID- 24312599
TI  - Characteristics and function of sulfur dioxygenase in Echiuran worm Urechis
      unicinctus.
AB  - BACKGROUND: Sulfide is a common toxin to animals and is abundant in coastal and
      aquatic sediments. Sulfur dioxygenase (SDO) is thought to be the key enzyme
      involved in sulfide oxidation in some organisms. The echiuran worm, Urechis
      unicinctus, inhabits coastal sediment and tolerates high concentrations of
      sulfide. The SDO is presumably important for sulfide tolerance in U. unicinctus.
      RESULTS: The full-length cDNA of SDO from the echiuran worm U. unicinctus, proven
      to be located in the mitochondria, was cloned and the analysis of its sequence
      suggests that it belongs to the metallo-beta-lactamase superfamily. The enzyme
      was produced using an E. coli expression system and the measured activity is
      approximately 0.80 U mg protein(-1). Furthermore, the expression of four sub
      segments of the U. unicinctus SDO was accomplished leading to preliminary
      identification of functional domains of the enzyme. The identification of the
      conserved metal I (H113, H115, H169 and D188), metal II (D117, H118, H169 and
      H229) as well as the potential glutathione (GSH) (R197, Y231, M279 and I283)
      binding sites was determined by enzyme activity and GSH affinity measurements.
      The key residues responsible for SDO activity were identified by analysis of
      simultaneous mutations of residues D117 and H118 located close to the metal II
      binding site. CONCLUSION: The recombinant SDO from U. unicinctus was produced,
      purified and characterized. The metal binding sites in the SDO were identified
      and Y231 recognized as the mostly important amino acid residue for GSH binding.
      Our results show that SDO is located in the mitochondria where it plays an
      important role in sulfide detoxification of U. unicinctus.

PMID- 24312600
TI  - Epigenetic regulation of alphaA-crystallin in high myopia-induced dark nuclear
      cataract.
AB  - PURPOSE: To assess the etiology of early-onset dark nucleus in high-myopic
      patients and its relationship with the epigenetic regulation of alphaA-crystallin
      (CRYAA). METHODS: We reviewed clinical data from patients who underwent cataract
      surgery at our center in 2012. Lens epithelial samples were collected during
      capsulorhexis, whereas young lens epithelium was donated. Cataract type and
      severity were graded according to the Lens Opacity Classification System III
      (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the
      CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color
      (NC) 2-3; High-Myopic Cataract (HMC) NC2-3; ARC NC5-6; HMC NC5-6; and in young
      lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain
      reaction (PCR), reverse transcription PCR, and immunohistochemistry. RESULTS: The
      odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence
      interval: 3.98-6.69; p<0.001). CpG islands in lens epithelial CRYAA promoter in
      the HMC NC5-6 Group exhibited the highest methylation of all the groups, but no
      statistically significant differences were evident between the HMC NC2-3 and ARC
      NC2-3 Groups. Likewise, CRYAA mRNA and protein levels in the HMC NC5-6 Group were
      significantly lower than the ARC NC5-6 Group and high-myopic controls.
      CONCLUSIONS: High myopia is a risk factor for dark nucleus. Downregulation of
      CRYAA via the hypermethylation of CpG islands in its promoter could underlie the
      earlier onset of dark nucleus in high-myopic patients.

PMID- 24312601
TI  - Fingolimod (FTY720) stimulates Ca(2+)/calcineurin signaling in fission yeast.
AB  - Fingolimod hydrochloride (FTY720) is the first in class of sphingosine 1
      phosphate (S1P) receptor modulator approved to treat multiple sclerosis via down
      regulation of G protein-coupled S1P receptor 1 by its phosphorylated form (FTY720
      P). Many studies have revealed that FTY720 exerts various biological effects,
      including antitumor activities, angiogenesis inhibition, Ca(2+) mobilization and
      apoptosis, independently of S1P receptors. However, the exact mechanisms
      underlying their effects or signaling pathways mediated by FTY720 have not been
      completely established. To gain further insights into molecular mechanisms of
      FTY720 action, the effect of FTY720 on Ca(2+) signaling in fission yeast was
      analyzed. The addition of Ca(2+) enhanced the sensitivity induced by FTY720, and
      mutants lacking genes required for calcium homeostasis, including calcineurin and
      its downstream transcription factor, Ppb1-responsive zinc finger protein (Prz1),
      were hypersensitive to FTY720 and CaCl2. The effect of FTY720 on calcineurin
      signaling was monitored by utilizing a luciferase reporter construct fused to
      three tandem repeats of the calcineurin-dependent response element (CDRE), which
      gives an accurate measure of calcineurin activity. The addition of FTY720
      increased calcineurin activity as well as Ca(2+) influx in a concentration
      dependent manner. Notably, the FTY720-mediated Ca(2+) influx and calcineurin
      activation were reduced markedly by the deletion of yam8 (+) or cch1 (+) encoding
      putative subunits of a Ca(2+) channel. Consistently, the deletion of Pmk1 mitogen
      activated protein kinase (MAPK), which plays an important role in the activation
      of the Yam8/Cch1 channel, markedly decreased the intracellular Ca(2+) levels upon
      FTY720 treatment. These results suggest that the FTY720-stimulated
      Ca(2+)/calcineurin signaling activation partly involves the Yam8/Cch1 channel in
      fission yeast. 

PMID- 24312602
TI  - Limited internal radiation exposure associated with resettlements to a radiation
      contaminated homeland after the Fukushima Daiichi nuclear disaster.
AB  - Resettlement to their radiation-contaminated hometown could be an option for
      people displaced at the time of a nuclear disaster; however, little information
      is available on the safety implications of these resettlement programs. Kawauchi
      village, located 12-30 km southwest of the Fukushima Daiichi nuclear power plant,
      was one of the 11 municipalities where mandatory evacuation was ordered by the
      central government. This village was also the first municipality to organize the
      return of the villagers. To assess the validity of the Kawauchi villagers'
      resettlement program, the levels of internal Cesium (Cs) exposures were
      comparatively measured in returnees, commuters, and non-returnees among the
      Kawauchi villagers using a whole body counter. Of 149 individuals, 5 villagers
      had traceable levels of Cs exposure; the median detected level was 333 Bq/body
      (range, 309-1050 Bq/kg), and 5.3 Bq/kg (range, 5.1-18.2 Bq/kg). Median annual
      effective doses of villagers with traceable Cs were 1.1 x 10(-2) mSv/y (range,
      1.0 x 10(-2)-4.1 x 10(-2) mSv/y). Although returnees had higher chances of
      consuming locally produced vegetables, Cochran-Mantel-Haenszel test showed that
      their level of internal radiation exposure was not significantly higher than that
      in the other 2 groups (p=0.643). The present findings in Kawauchi village imply
      that it is possible to maintain internal radiation exposure at very low levels
      even in a highly radiation-contaminated region at the time of a nuclear disaster.
      Moreover, the risks for internal radiation exposure could be limited with a
      strict food control intervention after resettlement to the radiation-contaminated
      village. It is crucial to establish an adequate number of radio-contaminated
      testing sites within the village, to provide immediate test result feedback to
      the villagers, and to provide education regarding the importance of re-testing in
      reducing the risk of high internal radiation exposure. 

PMID- 24312603
TI  - A silent exonic SNP in kdm3a affects nucleic acids structure but does not
      regulate experimental autoimmune encephalomyelitis.
AB  - Defining genetic variants that predispose for diseases is an important initiative
      that can improve biological understanding and focus therapeutic development.
      Genetic mapping in humans and animal models has defined genomic regions
      controlling a variety of phenotypes known as quantitative trait loci (QTL).
      Causative disease determinants, including single nucleotide polymorphisms (SNPs),
      lie within these regions and can often be identified through effects on gene
      expression. We previously identified a QTL on rat chromosome 4 regulating
      macrophage phenotypes and immune-mediated diseases including experimental
      autoimmune encephalomyelitis (EAE). Gene analysis and a literature search
      identified lysine-specific demethylase 3A (Kdm3a) as a potential regulator of
      these phenotypes. Genomic sequencing determined only two synonymous SNPs in
      Kdm3a. The silent synonymous SNP in exon 15 of Kdm3a caused problems with
      quantitative PCR detection in the susceptible strain through reduced
      amplification efficiency due to altered secondary cDNA structure. Shape
      Probability Shift analysis predicted that the SNP often affects RNA folding;
      thus, it may impact protein translation. Despite these differences in rats,
      genetic knockout of Kdm3a in mice resulted in no dramatic effect on immune system
      development and activation or EAE susceptibility and severity. These results
      provide support for tools that analyze causative SNPs that impact nucleic acid
      structures. 

PMID- 24312604
TI  - Comprehensive analysis of gene expression profiles of the beet armyworm
      Spodoptera exigua larvae challenged with Bacillus thuringiensis Vip3Aa toxin.
AB  - Host-pathogen interactions result in complex relationship, many aspects of which
      are not completely understood. Vip proteins, which are Bacillus thuringensis (Bt)
      insecticidal toxins produced during the vegetative stage, are selectively
      effective against specific insect pests. This new group of Bt proteins represents
      an interesting alternative to the classical Bt Cry toxins because current data
      suggests that they do not share the same mode of action. We have designed and
      developed a genome-wide microarray for the beet armyworm Spodoptera exigua, a
      serious lepidopteran pest of many agricultural crops, and used it to better
      understand how lepidopteran larvae respond to the treatment with the insecticidal
      protein Vip3Aa. With this approach, the goal of our study was to evaluate the
      changes in gene expression levels caused by treatment with sublethal doses of
      Vip3Aa (causing 99% growth inhibition) at 8 and 24 h after feeding. Results
      indicated that the toxin provoked a wide transcriptional response, with 19% of
      the microarray unigenes responding significantly to treatment. The number of up-
      and down-regulated unigenes was very similar. The number of genes whose
      expression was regulated at 8 h was similar to the number of genes whose
      expression was regulated after 24 h of treatment. The up-regulated sequences were
      enriched for genes involved in innate immune response and in pathogen response
      such as antimicrobial peptides (AMPs) and repat genes. The down-regulated
      sequences were mainly unigenes with homology to genes involved in metabolism.
      Genes related to the mode of action of Bt Cry proteins were found, in general, to
      be slightly overexpressed. The present study is the first genome-wide analysis of
      the response of lepidopteran insects to Vip3Aa intoxication. An insight into the
      molecular mechanisms and components related to Vip intoxication will allow
      designing of more effective management strategies for pest control. 

PMID- 24312605
TI  - PARP inhibition attenuates acute kidney allograft rejection by suppressing cell
      death pathways and activating PI-3K-Akt cascade.
AB  - BACKGROUND: Novel immunosuppressive therapy facilitates long term allograft
      survival, but acute tubular necrosis and ischemia-reperfusion during
      transplantation can compromise allograft function. These processes are related to
      oxidative stress which activates poly- (ADP-ribose) polymerase (PARP)
      contributing to the activation of cell death pathways. Here we raised the
      possibility that PARP inhibition curbs cell death pathways and shifts kinase
      signaling to improved graft survival. METHODS FINDINGS: In an acute rat kidney
      rejection model, we provided evidence that the PARP inhibitor 4-hydroxy
      quinazoline (4OHQ) attenuates rejection processes initiated oxidative/nitrosative
      stress, nuclear poly-ADP-ribosylation and the disintegration of the tubulo
      interstitial structures. The PARP inhibitor attenuated rejection processes
      induced pro-apoptotic pathways by increasing Bcl-2/Bax ratio and suppressing pro
      apoptotic t-Bid levels. In transplanted kidneys, the cell death inducing JNK1/2
      is normally activated, but PARP inhibition suppressed this activation with having
      only modest effects on ERK1/2 and p38 MAP kinases. In untreated transplanted
      kidneys, no significant alterations were detected in the cytoprotective PI-3K-Akt
      pathway, but the PARP inhibitor significantly activated Akt (by S473
      phosphorylation) and suppressed GSK-3beta, as well as activated acute NF-kappaB
      activation contributing to graft protection. CONCLUSION: These data show the
      protective role of PARP inhibition on graft survival by attenuating poly-ADP
      ribosylation, oxidative stress, suppressing pro-apoptotic and increasing anti
      apoptotic protein level, and by shifting MAP kinases and PI-3-K-Akt pathways to
      cytoprotective direction. Thus, addition of PARP inhibitors to standard
      immunosuppressive therapies during kidney transplantation may provide increased
      protection to prolong graft survival.

PMID- 24312606
TI  - Habitat hydrology and geomorphology control the distribution of malaria vector
      larvae in rural Africa.
AB  - BACKGROUND: Larval source management is a promising component of integrated
      malaria control and elimination. This requires development of a framework to
      target productive locations through process-based understanding of habitat
      hydrology and geomorphology. METHODS: We conducted the first catchment scale
      study of fine resolution spatial and temporal variation in Anopheles habitat and
      productivity in relation to rainfall, hydrology and geomorphology for a high
      malaria transmission area of Tanzania. RESULTS: Monthly aggregates of rainfall,
      river stage and water table were not significantly related to the abundance of
      vector larvae. However, these metrics showed strong explanatory power to predict
      mosquito larval abundances after stratification by water body type, with a clear
      seasonal trend for each, defined on the basis of its geomorphological setting and
      origin. CONCLUSION: Hydrological and geomorphological processes governing the
      availability and productivity of Anopheles breeding habitat need to be understood
      at the local scale for which larval source management is implemented in order to
      effectively target larval source interventions. Mapping and monitoring these
      processes is a well-established practice providing a tractable way forward for
      developing important malaria management tools.

PMID- 24312607
TI  - In vitro and in vivo evaluation of a (18)F-labeled high affinity NOTA conjugated
      bombesin antagonist as a PET ligand for GRPR-targeted tumor imaging.
AB  - Expression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer
      suggests that this receptor can be used as a potential molecular target to
      visualize and treat these tumors. We have previously investigated an antagonist
      analog of bombesin (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26) conjugated
      to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethylene glycol
      (PEG2) spacer (NOTA-P2-RM26) labeled with (68)Ga and (111)In. We found that this
      conjugate has favorable properties for in vivo imaging of GRPR-expression. The
      focus of this study was to develop a (18)F-labelled PET agent to visualize GRPR.
      NOTA-P2-RM26 was labeled with (18)F using aluminum-fluoride chelation. Stability,
      in vitro binding specificity and cellular processing tests were performed. The
      inhibition efficiency (IC50) of the [(nat)F]AlF-NOTA-P2-RM26 was compared to that
      of the (nat)Ga-loaded peptide using (125)I-Tyr(4)-BBN as the displacement
      radioligand. The pharmacokinetics and in vivo binding specificity of the compound
      were studied. NOTA-P2-RM26 was labeled with (18)F within 1 h (60-65% decay
      corrected radiochemical yield, 55 GBq/umol). The radiopeptide was stable in
      murine serum and showed high specific binding to PC-3 cells. [(nat)F]AlF-NOTA-P2
      RM26 showed a low nanomolar inhibition efficiency (IC50=4.4+/-0.8 nM). The
      internalization rate of the tracer was low. Less than 14% of the cell-bound
      radioactivity was internalized after 4 h. The biodistribution of [(18)F]AlF-NOTA
      P2-RM26 demonstrated rapid blood clearance, low liver uptake and low kidney
      retention. The tumor uptake at 3 h p.i. was 5.5+/-0.7 %ID/g, and the tumor-to
      blood, -muscle and -bone ratios were 87+/-42, 159+/-47, 38+/-16, respectively.
      The uptake in tumors, pancreas and other GRPR-expressing organs was significantly
      reduced when excess amount of non-labeled peptide was co-injected. The low uptake
      in bone suggests a high in vivo stability of the Al-F bond. High contrast PET
      image was obtained 3 h p.i. The initial biological results suggest that
      [(18)F]AlF-NOTA-P2-RM26 is a promising candidate for PET imaging of GRPR in vivo.

PMID- 24312608
TI  - Factors determining patient-prosthesis mismatch after aortic valve replacement--a
      prospective cohort study.
AB  - OBJECTIVE: "Patient-prosthesis mismatch" (PPM) after aortic valve replacement
      (AVR) has been reported to increase morbidity and mortality. Although algorithms
      have been developed to avoid PPM, factors favouring its occurrence have not been
      well defined. DESIGN AND SETTING: This was a prospective cohort study performed
      at the Medical University of Vienna. PATIENTS: 361 consecutive patients who
      underwent aortic valve replacement for isolated severe aortic stenosis were
      enrolled. MAIN OUTCOME MEASURES: Patient- as well as prosthesis-related factors
      determining the occurrence of moderate and severe PPM (defined as effective
      orifice area indexed to body surface area <= 0.8 cm(2)/m(2)) were studied.
      RESULTS: Postoperatively, 172 patients (48%) were diagnosed with PPM. The fact
      that predominantly female patients were affected (58% with PPM diagnosis in women
      versus 36% in men, p<0.001) was explained by the finding that they had smaller
      aortic root diameters (30.5+/-4.7 mm versus 35.3+/-4.2 mm, p<0.0001) and a higher
      proportion of bioprosthetic valves (82% versus 62%, p<0.0001), both independent
      predictors of PPM (aortic root diameter: OR 0.009 [95% CI, 0.004;0.013]; p =
      0.0003, presence of bioprosthetic valve: OR 0.126 [95% CI, 0.078;0.175];
      p<0.0001). CONCLUSIONS: The occurrence of PPM is determined by aortic root
      diameter and prosthesis type. Novel sutureless bioprostheses with optimized
      hemodynamic performance or transcatheter aortic valves may become a promising
      alternative to conventional bioprosthetic valves in the future.

PMID- 24312609
TI  - A coastal seawater temperature dataset for biogeographical studies: large biases
      between in situ and remotely-sensed data sets around the Coast of South Africa.
AB  - Gridded SST products developed particularly for offshore regions are increasingly
      being applied close to the coast for biogeographical applications. The purpose of
      this paper is to demonstrate the dangers of doing so through a comparison of
      reprocessed MODIS Terra and Pathfinder v5.2 SSTs, both at 4 km resolution, with
      instrumental in situ temperatures taken within 400 m from the coast. We report
      large biases of up to +6 degrees C in places between satellite-derived and in
      situ climatological temperatures for 87 sites spanning the entire ca. 2 700 km of
      the South African coastline. Although biases are predominantly warm (i.e. the
      satellite SSTs being higher), smaller or even cold biases also appear in places,
      especially along the southern and western coasts of the country. We also
      demonstrate the presence of gradients in temperature biases along shore-normal
      transects - generally SSTs extracted close to the shore demonstrate a smaller
      bias with respect to the in situ temperatures. Contributing towards the magnitude
      of the biases are factors such as SST data source, proximity to the shore, the
      presence/absence of upwelling cells or coastal embayments. Despite the generally
      large biases, from a biogeographical perspective, species distribution retains a
      correlative relationship with underlying spatial patterns in SST, but in order to
      arrive at a causal understanding of the determinants of biogeographical patterns
      we suggest that in shallow, inshore marine habitats, temperature is best measured
      directly. 

PMID- 24312610
TI  - Robotic versus open gastrectomy for gastric cancer: a meta-analysis.
AB  - AIM: To evaluate the safety and efficacy of robotic gastrectomy versus open
      gastrectomy for gastric cancer. METHODS: A comprehensive search of PubMed,
      EMBASE, Cochrane Library, and Web of Knowledge was performed. Systematic review
      was carried out to identify studies comparing robotic gastrectomy and open
      gastrectomy in gastric cancer. Intraoperative and postoperative outcomes were
      also analyzed to evaluate the safety and efficacy of the surgery. A fixed effects
      model or a random effects model was utilized according to the heterogeneity.
      RESULTS: Four studies involving 5780 patients with 520 (9.00%) cases of robotic
      gastrectomy and 5260 (91.00%) cases of open gastrectomy were included in this
      meta-analysis. Compared to open gastrectomy, robotic gastrectomy has a
      significantly longer operation time (weighted mean differences (WMD) =92.37, 95%
      confidence interval (CI): 55.63 to 129.12, P<0.00001), lower blood loss (WMD: 
      126.08, 95% CI: -189.02 to -63.13, P<0.0001), and shorter hospital stay (WMD = 
      2.87; 95% CI: -4.17 to -1.56; P<0.0001). No statistical difference was noted
      based on the rate of overall postoperative complication, wound infection,
      bleeding, number of harvested lymph nodes, anastomotic leakage and postoperative
      mortality rate. CONCLUSIONS: The results of this meta-analysis suggest that
      robotic gastrectomy is a better alternative technique to open gastrectomy for
      gastric cancer. However, more prospective, well-designed, multicenter, randomized
      controlled trials are necessary to further evaluate the safety and efficacy as
      well as the long-term outcome.

PMID- 24312611
TI  - PLGA-carbon nanotube conjugates for intercellular delivery of caspase-3 into
      osteosarcoma cells.
AB  - Cancer has arisen to be of the most prominent health care issues across the world
      in recent years. Doctors have used physiological intervention as well as chemical
      and radioactive therapeutics to treat cancer thus far. As an alternative to
      current methods, gene delivery systems with high efficiency, specificity, and
      safety that can reduce side effects such as necrosis of tissue are under
      development. Although viral vectors are highly efficient, concerns have arisen
      from the fact that viral vectors are sourced from lethal diseases. With this in
      mind, rod shaped nano-materials such as carbon nanotubes (CNTs) have become an
      attractive option for drug delivery due to the enhanced permeability and
      retention effect in tumors as well as the ability to penetrate the cell membrane.
      Here, we successfully engineered poly (lactic-co-glycolic) (PLGA) functionalized
      CNTs to reduce toxicity concerns, provide attachment sites for pro-apoptotic
      protein caspase-3 (CP3), and tune the temporal release profile of CP3 within bone
      cancer cells. Our results showed that CP3 was able to attach to functionalized
      CNTs, forming CNT-PLGA-CP3 conjugates. We show this conjugate can efficiently
      transduce cells at dosages as low as 0.05 MUg/ml and suppress cell proliferation
      up to a week with no further treatments. These results are essential to showing
      the capabilities of PLGA functionalized CNTs as a non-viral vector gene delivery
      technique to tune cell fate. 

PMID- 24312612
TI  - Inosine enhances axon sprouting and motor recovery after spinal cord injury.
AB  - Although corticospinal tract axons cannot regenerate long distances after spinal
      cord injury, they are able to sprout collateral branches rostral to an injury
      site that can help form compensatory circuits in cases of incomplete lesions. We
      show here that inosine enhances the formation of compensatory circuits after a
      dorsal hemisection of the thoracic spinal cord in mature rats and improves
      coordinated limb use. Inosine is a naturally occurring metabolite of adenosine
      that crosses the cell membrane and, in neurons, activates Mst3b, a protein kinase
      that is part of a signal transduction pathway that regulates axon outgrowth.
      Compared to saline-treated controls, rats with dorsal hemisections that were
      treated with inosine showed three times as many synaptic contacts between
      corticospinal tract collaterals and long propriospinal interneurons that project
      from the cervical cord to the lumbar level. Inosine-treated rats also showed
      stronger serotonergic reinnervation of the lumbar cord than saline-treated
      controls, and performed well above controls in both open-field testing and a
      horizontal ladder rung-walking test. Inosine was equally effective whether
      delivered intracranially or intravenously, and has been shown to be safe for
      other indications in humans. Thus, inosine might be a useful therapeutic for
      improving outcome after spinal cord injury. 

PMID- 24312613
TI  - Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells
      deficiency through activation-induced cell death.
AB  - BACKGROUND: Dietary lipids play an important role in the progression of non
      alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune
      response. AIMS: The present study was to investigate the effect of lipid on
      Kupffer cells phenotype and function in vivo and in vitro. And further to
      investigate the impact of lipid on ability of Kupffer cell lipid antigen
      presentation to activate NKT cells. METHODS: Wild type male C57BL/6 mice were fed
      either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT
      cell number and cytokine gene expression were evaluated. Antigen presentation
      assay was performed with Kupffer cells treated with certain fatty acids in vitro
      and co-cultured with NKT cells. RESULTS: High-fat diet induced hepatosteatosis,
      significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid
      treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene
      expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer
      cells expressed high levels of CD1d on cell surface and only presented exogenous
      lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen
      and activate NKT cells was enhanced after lipid treatment. In addition, pro
      inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells
      activation-induced apoptosis and necrosis. CONCLUSION: High-fat diet increase
      Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory
      activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and
      cell death, which lead to further hepatic NKT cell deficiency in the development
      of NAFLD.

PMID- 24312614
TI  - Millennial-scale temperature change velocity in the continental northern
      Neotropics.
AB  - Climate has been inherently linked to global diversity patterns, and yet no
      empirical data are available to put modern climate change into a millennial-scale
      context. High tropical species diversity has been linked to slow rates of climate
      change during the Quaternary, an assumption that lacks an empirical foundation.
      Thus, there is the need for quantifying the velocity at which the bioclimatic
      space changed during the Quaternary in the tropics. Here we present rates of
      climate change for the late Pleistocene and Holocene from Mexico and Guatemala.
      An extensive modern pollen survey and fossil pollen data from two long
      sedimentary records (30,000 and 86,000 years for highlands and lowlands,
      respectively) were used to estimate past temperatures. Derived temperature
      profiles show a parallel long-term trend and a similar cooling during the Last
      Glacial Maximum in the Guatemalan lowlands and the Mexican highlands. Temperature
      estimates and digital elevation models were used to calculate the velocity of
      isotherm displacement (temperature change velocity) for the time period contained
      in each record. Our analyses showed that temperature change velocities in
      Mesoamerica during the late Quaternary were at least four times slower than
      values reported for the last 50 years, but also at least twice as fast as those
      obtained from recent models. Our data demonstrate that, given extremely high
      temperature change velocities, species survival must have relied on either
      microrefugial populations or persistence of suppressed individuals. Contrary to
      the usual expectation of stable climates being associated with high diversity,
      our results suggest that Quaternary tropical diversity was probably maintained by
      centennial-scale oscillatory climatic variability that forestalled competitive
      exclusion. As humans have simplified modern landscapes, thereby removing
      potential microrefugia, and climate change is occurring monotonically at a very
      high velocity, extinction risk for tropical species is higher than at any time in
      the last 86,000 years. 

PMID- 24312615
TI  - Kinetics of expansion of human limbal epithelial progenitor cells in primary
      culture of explants without feeders.
AB  - The aims of this study were to determine whether human limbal explant cultures
      without feeder cells result in expansion of epithelial progenitors and to
      estimate the optimal expansion time for progenitor cells. Limbal explants from
      ten human corneas were cultured for 7, 9, 11, 14, 18, and 21 days. Limbal
      explants from two corneas were enzymatically dissociated or directly cultured for
      14 days. Progenitor cells were characterized by their ability to form colonies,
      by immunocytochemistry, and by quantitative real-time polymerase chain reaction.
      Colonies were identified after 9, 11, 14, and 18 days of culture, but not after
      21 days. The number of colonies per explant was significantly higher after 14
      days than after 9 and 21 days. The mean percentage of seeded cells giving rise to
      clones was 4.03% after 14 days of culture and 0.36% for non-cultured dissociated
      limbal epithelial cells. The number of cells giving rise to clones per cornea
      significantly increased from an average of 2275 for non-cultured cells to 24266
      for cells cultured for 14 days. Immunocytochemical analysis detected positive
      staining for cytokeratin (CK) 3, CK5/6/8/10/13/18, CK19, vimentin, p63, and
      p63alpha, in both cultures and clones. CK3 expression increased significantly
      with culture time. Transcript expression was observed for CK3, CK19, vimentin,
      and Delta N p63alpha at each culture time point, both in cultures and clones. The
      optimal culture time for limbal explants in cholera toxin-free Green medium
      without feeder cells was 14 days leading to the expansion of progenitors. 

PMID- 24312616
TI  - Structural and functional analysis of human SOD1 in amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with
      familial inheritance (fALS) in 5% to 10% of cases; 25% of those are caused by
      mutations in the superoxide dismutase 1 (SOD1) protein. More than 100 mutations
      in the SOD1 gene have been associated with fALS, altering the geometry of the
      active site, protein folding and the interaction between monomers. We performed a
      functional analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in
      124 fALS SOD1 mutants. Eleven different algorithms were used to estimate the
      functional impact of the replacement of one amino acid on protein structure:
      SNPs&GO, PolyPhen-2, SNAP, PMUT, Sift, PhD-SNP, nsSNPAnalyzer, TANGO, WALTZ,
      LIMBO and FoldX. For the structural analysis, theoretical models of 124 SNPs of
      SOD1 were created by comparative modeling using the MHOLline workflow, which
      includes Modeller and Procheck. Models were aligned with the native protein by
      the TM-align algorithm. A human-curated database was developed using the server
      side include in Java, JMOL. The results of this functional analysis indicate that
      the majority of the 124 natural mutants are harmful to the protein structure and
      thus corroborate the correlation between the reported mutations and fALS. In the
      structural analysis, all models showed conformational changes when compared to
      wild-type SOD1, and the degree of structural alignment varied between them. The
      SOD1 database converge structural and functional analyses of SOD1; it is a vast
      resource for the molecular analysis of amyotrophic lateral sclerosis, which
      allows the user to expand his knowledge on the molecular basis of the disease.
      The SOD1 database is available at http://bioinfogroup.com/database. 

PMID- 24312617
TI  - Identifying cytochrome p450 functional networks and their allosteric regulatory
      elements.
AB  - Cytochrome P450 (CYP) enzymes play key roles in drug metabolism and adverse drug
      drug interactions. Despite tremendous efforts in the past decades, essential
      questions regarding the function and activity of CYPs remain unanswered. Here, we
      used a combination of sequence-based co-evolutionary analysis and structure-based
      anisotropic thermal diffusion (ATD) molecular dynamics simulations to detect
      allosteric networks of amino acid residues and characterize their biological and
      molecular functions. We investigated four CYP subfamilies (CYP1A, CYP2D, CYP2C,
      and CYP3A) that are involved in 90% of all metabolic drug transformations and
      identified four amino acid interaction networks associated with specific CYP
      functionalities, i.e., membrane binding, heme binding, catalytic activity, and
      dimerization. Interestingly, we did not detect any co-evolved substrate-binding
      network, suggesting that substrate recognition is specific for each subfamily.
      Analysis of the membrane binding networks revealed that different CYP proteins
      adopt different membrane-bound orientations, consistent with the differing
      substrate preference for each isoform. The catalytic networks were associated
      with conservation of catalytic function among CYP isoforms, whereas the
      dimerization network was specific to different CYP isoforms. We further applied
      low-temperature ATD simulations to verify proposed allosteric sites associated
      with the heme-binding network and their role in regulating metabolic fate. Our
      approach allowed for a broad characterization of CYP properties, such as membrane
      interactions, catalytic mechanisms, dimerization, and linking these to groups of
      residues that can serve as allosteric regulators. The presented combined co
      evolutionary analysis and ATD simulation approach is also generally applicable to
      other biological systems where allostery plays a role. 

PMID- 24312618
TI  - Structure-function features of a Mycoplasma glycolipid synthase derived from
      structural data integration, molecular simulations, and mutational analysis.
AB  - Glycoglycerolipids are structural components of mycoplasma membranes with a
      fundamental role in membrane properties and stability. Their biosynthesis is
      mediated by glycosyltransferases (GT) that catalyze the transfer of glycosyl
      units from a sugar nucleotide donor to diacylglycerol. The essential function of
      glycolipid synthases in mycoplasma viability, and the absence of
      glycoglycerolipids in animal host cells make these GT enzymes a target for drug
      discovery by designing specific inhibitors. However, rational drug design has
      been hampered by the lack of structural information for any mycoplasma GT. Most
      of the annotated GTs in pathogenic mycoplasmas belong to family GT2. We had
      previously shown that MG517 in Mycoplasma genitalium is a GT-A family GT2
      membrane-associated glycolipid synthase. We present here a series of structural
      models of MG517 obtained by homology modeling following a multiple-template
      approach. The models have been validated by mutational analysis and refined by
      long scale molecular dynamics simulations. Based on the models, key structure
      function relationships have been identified: The N-terminal GT domain has a GT-A
      topology that includes a non-conserved variable region involved in acceptor
      substrate binding. Glu193 is proposed as the catalytic base in the GT mechanism,
      and Asp40, Tyr126, Tyr169, Ile170 and Tyr218 define the substrates binding site.
      Mutation Y169F increases the enzyme activity and significantly alters the
      processivity (or sequential transferase activity) of the enzyme. This is the
      first structural model of a GT-A glycoglycerolipid synthase and provides
      preliminary insights into structure and function relationships in this family of
      enzymes. 

PMID- 24312619
TI  - Genomic DNA enrichment using sequence capture microarrays: a novel approach to
      discover sequence nucleotide polymorphisms (SNP) in Brassica napus L.
AB  - Targeted genomic selection methodologies, or sequence capture, allow for DNA
      enrichment and large-scale resequencing and characterization of natural genetic
      variation in species with complex genomes, such as rapeseed canola (Brassica
      napus L., AACC, 2n=38). The main goal of this project was to combine sequence
      capture with next generation sequencing (NGS) to discover single nucleotide
      polymorphisms (SNPs) in specific areas of the B. napus genome historically
      associated (via quantitative trait loci -QTL- analysis) to traits of agronomical
      and nutritional importance. A 2.1 million feature sequence capture platform was
      designed to interrogate DNA sequence variation across 47 specific genomic
      regions, representing 51.2 Mb of the Brassica A and C genomes, in ten diverse
      rapeseed genotypes. All ten genotypes were sequenced using the 454 Life Sciences
      chemistry and to assess the effect of increased sequence depth, two genotypes
      were also sequenced using Illumina HiSeq chemistry. As a result, 589,367
      potentially useful SNPs were identified. Analysis of sequence coverage indicated
      a four-fold increased representation of target regions, with 57% of the filtered
      SNPs falling within these regions. Sixty percent of discovered SNPs corresponded
      to transitions while 40% were transversions. Interestingly, fifty eight percent
      of the SNPs were found in genic regions while 42% were found in intergenic
      regions. Further, a high percentage of genic SNPs was found in exons (65% and 64%
      for the A and C genomes, respectively). Two different genotyping assays were used
      to validate the discovered SNPs. Validation rates ranged from 61.5% to 84% of
      tested SNPs, underpinning the effectiveness of this SNP discovery approach. Most
      importantly, the discovered SNPs were associated with agronomically important
      regions of the B. napus genome generating a novel data resource for research and
      breeding this crop species. 

PMID- 24312620
TI  - Frequent detection of latent tuberculosis infection among aged underground hard
      coal miners in the absence of recent tuberculosis exposure.
AB  - BACKGROUND: Miners are at particular risk for tuberculosis (TB) infection due to
      exposure to silica dust and silicosis. The objectives of the present
      observational cohort study were to determine the prevalence of latent TB
      infection (LTBI) among aged German underground hard coal miners with silicosis or
      chronic obstructive pulmonary disease (COPD) using two commercial interferon
      gamma release assays (IGRAs) and to compare their performance with respect to
      predictors of test positivity. METHODS: Between October 2008 and June 2010,
      miners were consecutively recruited when routinely attending pneumoconiosis
      clinics for an expert opinion. Both IGRAs, the QuantiFERON(r)-TB Gold In-Tube
      (QFT) and the T-SPOT(r).TB (T-SPOT), were performed at baseline. A standardized
      clinical interview was conducted at baseline and at follow-up. The cohort was
      prospectively followed regarding the development of active TB for at least two
      years after inclusion of the last study subject. Independent predictors of IGRA
      positivity were calculated using logistic regression. RESULTS: Among 118 subjects
      (mean age 75 years), none reported recent exposure to TB. Overall, the QFT and
      the T-SPOT yielded similarly high rates of positive results (QFT: 46.6%; 95%
      confidence interval 37.6-55.6%; T-SPOT: 61.0%; 95% confidence interval 52.2
      69.8%). Positive results were independently predicted by age >=80 years and
      foreign country of birth for both IGRAs. In addition, radiological evidence of
      prior healed TB increased the chance of a positive QFT result fivefold. While 28
      subjects were lost to follow-up, no cases of active TB occurred among 90 subjects
      during an average follow-up of >2 years. CONCLUSIONS: Considering the high
      prevalence of LTBI, the absence of recent TB exposure, and the currently low TB
      incidence in Germany, our study provides evidence for the persistence of specific
      interferon-gamma responses even decades after putative exposure. However, the
      clinical value of current IGRAs among our study population, although probably
      limited, remains uncertain.

PMID- 24312621
TI  - ROS stress resets circadian clocks to coordinate pro-survival signals.
AB  - Dysfunction of circadian clocks exacerbates various diseases, in part likely due
      to impaired stress resistance. It is unclear how circadian clock system responds
      toward critical stresses, to evoke life-protective adaptation. We identified a
      reactive oxygen species (ROS), H2O2 -responsive circadian pathway in mammals.
      Near-lethal doses of ROS-induced critical oxidative stress (cOS) at the branch
      point of life and death resets circadian clocks, synergistically evoking
      protective responses for cell survival. The cOS-triggered clock resetting and pro
      survival responses are mediated by transcription factor, central clock-regulatory
      BMAL1 and heat shock stress-responsive (HSR) HSF1. Casein kinase II (CK2) 
      mediated phosphorylation regulates dimerization and function of BMAL1 and HSF1 to
      control the cOS-evoked responses. The core cOS-responsive transcriptome includes
      CK2-regulated crosstalk between the circadian, HSR, NF-kappa-B-mediated anti
      apoptotic, and Nrf2-mediated anti-oxidant pathways. This novel circadian-adaptive
      signaling system likely plays fundamental protective roles in various ROS
      inducible disorders, diseases, and death. 

PMID- 24312622
TI  - MagFRET: the first genetically encoded fluorescent Mg2+ sensor.
AB  - Magnesium has important structural, catalytic and signaling roles in cells, yet
      few tools exist to image this metal ion in real time and at subcellular
      resolution. Here we report the first genetically encoded sensor for Mg(2+),
      MagFRET-1. This sensor is based on the high-affinity Mg(2+) binding domain of
      human centrin 3 (HsCen3), which undergoes a transition from a molten-globular apo
      form to a compactly-folded Mg(2+)-bound state. Fusion of Cerulean and Citrine
      fluorescent domains to the ends of HsCen3, yielded MagFRET-1, which combines a
      physiologically relevant Mg(2+) affinity (K d = 148 uM) with a 50% increase in
      emission ratio upon Mg(2+) binding due to a change in FRET efficiency between
      Cerulean and Citrine. Mutations in the metal binding sites yielded MagFRET
      variants whose Mg(2+) affinities were attenuated 2- to 100-fold relative to
      MagFRET-1, thus covering a broad range of Mg(2+) concentrations. In situ
      experiments in HEK293 cells showed that MagFRET-1 can be targeted to the cytosol
      and the nucleus. Clear responses to changes in extracellular Mg(2+) concentration
      were observed for MagFRET-1-expressing HEK293 cells when they were permeabilized
      with digitonin, whereas similar changes were not observed for intact cells.
      Although MagFRET-1 is also sensitive to Ca(2+), this affinity is sufficiently
      attenuated (K d of 10 uM) to make the sensor insensitive to known Ca(2+) stimuli
      in HEK293 cells. While the potential and limitations of the MagFRET sensors for
      intracellular Mg(2+) imaging need to be further established, we expect that these
      genetically encoded and ratiometric fluorescent Mg(2+) sensors could prove very
      useful in understanding intracellular Mg(2+) homeostasis and signaling. 

PMID- 24312623
TI  - Interacting proteins on human spermatozoa: adaptive evolution of the binding of
      semenogelin I to EPPIN.
AB  - Semenogelin I (SEMG1) is found in human semen coagulum and on the surface of
      spermatozoa bound to EPPIN. The physiological significance of the SEMG1/EPPIN
      interaction on the surface of spermatozoa is its capacity to modulate sperm
      progressive motility. The present study investigates the hypothesis that the
      interacting surface of SEMG1 and EPPIN co-evolved within the Hominoidea time
      scale, as a result of adaptive pressures applied by their roles in sperm
      protection and reproductive fitness. Our results indicate that some amino acid
      residues of SEMG1 and EPPIN possess a remarkable deficiency of variation among
      hominoid primates. We observe a distinct residue change unique to humans within
      the EPPIN sequence containing a SEMG1 interacting surface, namely His92. In
      addition, Bayes Empirical Bayes analysis for positive selection indicates that
      the SEMG1 Cys239 residue underwent positive selection in humans, probably as a
      consequence of its role in increasing the binding affinity of these interacting
      proteins. We confirm the critical role of Cys239 residue for SEMG1 binding to
      EPPIN and inhibition of sperm motility by showing that recombinant SEMG1 mutants
      in which Cys239 residue was changed to glycine, aspartic acid, histidine, serine
      or arginine have reduced capacity to interact to EPPIN and to inhibit human sperm
      motility in vitro. In conclusion, our results indicate that EPPIN and SEMG1
      rapidly co-evolved in primates due to their critical role in the modulation of
      sperm motility in the semen coagulum, providing unique insights into the
      molecular co-evolution of sperm surface interacting proteins. 

PMID- 24312625
TI  - Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro
      apoptotic function.
AB  - We reported recently that apoptosis-stimulating protein of p53 (ASPP) 2, an
      activator of p53, co-operates with oncogenic RAS to enhance the transcription and
      apoptotic function of p53. However, the detailed mechanism remains unknown. Here
      we show that ASPP2 is a novel substrate of mitogen-activated protein kinase
      (MAPK). Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased
      binding to p53 and increased transactivation of pro-apoptotic genes. In contrast,
      an ASPP2 phosphorylation mutant exhibits reduced p53 binding and fails to enhance
      transactivation and apoptosis. Thus phosphorylation of ASPP2 by RAS/MAPK pathway
      provides a novel link between RAS and p53 in regulating apoptosis. 

PMID- 24312624
TI  - Exendin-4 ameliorates traumatic brain injury-induced cognitive impairment in
      rats.
AB  - Traumatic brain injury represents a major public health issue that affects 1.7
      million Americans each year and is a primary contributing factor (30.5%) of all
      injury-related deaths in the United States. The occurrence of traumatic brain
      injury is likely underestimated and thus has been termed "a silent epidemic".
      Exendin-4 is a long-acting glucagon-like peptide-1 receptor agonist approved for
      the treatment of type 2 diabetes mellitus that not only effectively induces
      glucose-dependent insulin secretion to regulate blood glucose levels but also
      reduces apoptotic cell death of pancreatic beta-cells. Accumulating evidence also
      supports a neurotrophic and neuroprotective role of glucagon-like peptide-1 in an
      array of cellular and animal neurodegeneration models. In this study, we
      evaluated the neuroprotective effects of Exendin-4 using a glutamate toxicity
      model in vitro and fluid percussion injury in vivo. We found neuroprotective
      effects of Exendin-4 both in vitro, using markers of cell death, and in vivo,
      using markers of cognitive function, as assessed by Morris Water Maze. In
      combination with the reported benefits of ex-4 in other TBI models, these data
      support repositioning of Exendin-4 as a potential treatment for traumatic brain
      injury. 

PMID- 24312626
TI  - Synaptic symmetry increases coherence in a pair of excitable electronic neurons.
AB  - We study how the synaptic connections in a pair of excitable electronic neurons
      affect the coherence of their spike trains when the neurons are submitted to
      noise from independent sources. The coupling is provided by electronic circuits
      which mimic the dynamics of chemical AMPA synapses. In particular, we show that
      increasing the strength of an unidirectional synapse leads to a decrease of
      coherence in the post-synaptic neuron. More interestingly, we show that the
      decrease of coherence can be reverted if we add a synapse of sufficient strength
      in the reverse direction. Synaptic symmetry plays an important role in this
      process and, under the right choice of parameters, increases the network
      coherence beyond the value achieved at the resonance due to noise alone in
      uncoupled neurons. We also show that synapses with a longer time scale sharpen
      the dependency of the coherence on the synaptic symmetry. The results were
      reproduced by numerical simulations of a pair of synaptically coupled FitzHugh
      Nagumo models. 

PMID- 24312627
TI  - Apoptosis repressor with a CARD domain (ARC) restrains Bax-mediated pathogenesis
      in dystrophic skeletal muscle.
AB  - Myofiber wasting in muscular dystrophy has largely been ascribed to necrotic cell
      death, despite reports identifying apoptotic markers in dystrophic muscle. Here
      we set out to identify the contribution of canonical apoptotic pathways to
      skeletal muscle degeneration in muscular dystrophy by genetically deleting a
      known inhibitor of apoptosis, apoptosis repressor with a card domain (Arc), in
      dystrophic mouse models. Nol3 (Arc protein) genetic deletion in the dystrophic
      Sgcd or Lama2 null backgrounds showed exacerbated skeletal muscle pathology with
      decreased muscle performance compared with single null dystrophic littermate
      controls. The enhanced severity of the dystrophic phenotype associated with Nol3
      deletion was caspase independent but dependent on the mitochondria permeability
      transition pore (MPTP), as the inhibitor Debio-025 partially rescued skeletal
      muscle pathology in Nol3 (-/-) Sgcd (-/-) double targeted mice. Mechanistically,
      Nol3 (-/-) Sgcd (-/-) mice showed elevated total and mitochondrial Bax protein
      levels, as well as greater mitochondrial swelling, suggesting that Arc normally
      restrains the cell death effects of Bax in skeletal muscle. Indeed, knockdown of
      Arc in mouse embryonic fibroblasts caused an increased sensitivity to cell death
      that was fully blocked in Bax Bak1 (genes encoding Bax and Bak) double null
      fibroblasts. Thus Arc deficiency in dystrophic muscle exacerbates disease
      pathogenesis due to a Bax-mediated sensitization of mitochondria-dependent death
      mechanisms. 

PMID- 24312628
TI  - The E-wave deceleration rate E/DT outperforms the tissue Doppler-derived index
      E/e' in characterizing lung remodeling in heart failure with preserved ejection
      fraction.
AB  - BACKGROUND: Diastolic dysfunction in heart failure with preserved ejection
      fraction (HFpEF) may result in pulmonary congestion and lung remodeling. We
      evaluated the usefulness of major diastolic echocardiographic parameters and of
      the deceleration rate of early transmitral diastolic velocity (E/DT) in
      predicting lung remodeling in a rat model of HFpEF. METHODS AND RESULTS: Rats
      underwent aortic banding (AoB) to induce pressure overload (PO). Left ventricular
      hypertrophy fully developed 2 weeks after AoB. At 4 and 6 weeks, the lung weight
      to-body weight ratio (LW/BW), a sensitive marker for pulmonary congestion and
      remodeling, dramatically increased despite preserved fractional shortening,
      indicating the presence of HFpEF. The time course of LW/BW was well reflected by
      E/DT, by the ratio of early to late transmitral diastolic velocity (E/A) and the
      deceleration time of E (DT), but not by the ratio of transmitral to mitral
      annular early diastolic velocity (E/e'). In agreement, the best correlation with
      LW/BW was found for E/DT (r = 0.76; p<0.0001), followed by E/A (r = 0.69;
      p<0.0001), DT (r = -0.62; p<0.0001) and finally E/e' (r = 0.51; p<0.001).
      Furthermore, analysis of receiver-operating characteristic curves for the
      prediction of increased LW/BW revealed excellent area under the curve values for
      E/DT (AUC = 0.98) and DT (AUC = 0.95), which are significantly higher than that
      of E/e' (AUC = 0.82). In a second approach, we also found that the new parameter
      E/DT correlated well with right ventricular weight index and echocardiographic
      measures of right ventricular systolic function. CONCLUSIONS: The novel parameter
      E/DT outperforms the tissue Doppler index E/e' in detecting and monitoring lung
      remodeling induced by pressure overload. The results may provide a handy tool to
      point towards secondary lung disease in HFpEF and warrant further clinical
      investigations.

PMID- 24312629
TI  - Peptides corresponding to the predicted heptad repeat 2 domain of the feline
      coronavirus spike protein are potent inhibitors of viral infection.
AB  - BACKGROUND: Feline infectious peritonitis (FIP) is a lethal immune-mediated
      disease caused by feline coronavirus (FCoV). Currently, no therapy with proven
      efficacy is available. In searching for agents that may prove clinically
      effective against FCoV infection, five analogous overlapping peptides were
      designed and synthesized based on the putative heptad repeat 2 (HR2) sequence of
      the spike protein of FCoV, and the antiviral efficacy was evaluated. METHODS:
      Plaque reduction assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) cytotoxicity assay were performed in this study.
      Peptides were selected using a plaque reduction assay to inhibit Feline
      coronavirus infection. RESULTS: The results demonstrated that peptide (FP5) at
      concentrations below 20 MUM inhibited viral replication by up to 97%. The peptide
      (FP5) exhibiting the most effective antiviral effect was further combined with a
      known anti-viral agent, human interferon-alpha (IFN-alpha), and a significant
      synergistic antiviral effect was observed. CONCLUSION: Our data suggest that the
      synthetic peptide FP5 could serve as a valuable addition to the current FIP
      prevention methods.

PMID- 24312630
TI  - Endothelial progenitor cells promote directional three-dimensional endothelial
      network formation by secreting vascular endothelial growth factor.
AB  - Endothelial progenitor cell (EPC) transplantation induces the formation of new
      blood-vessel networks to supply nutrients and oxygen, and is feasible for the
      treatment of ischemia and cardiovascular diseases. However, the role of EPCs as a
      source of proangiogenic cytokines and consequent generators of an extracellular
      growth factor microenvironment in three-dimensional (3D) microvessel formation is
      not fully understood. We focused on the contribution of EPCs as a source of
      proangiogenic cytokines on 3D microvessel formation using an in vitro 3D network
      model. To create a 3D network model, EPCs isolated from rat bone marrow were
      sandwiched with double layers of collagen gel. Endothelial cells (ECs) were then
      cultured on top of the upper collagen gel layer. Quantitative analyses of EC
      network formation revealed that the length, number, and depth of the EC networks
      were significantly enhanced in a 3D model with ECs and EPCs compared to an EC
      monoculture. In addition, conditioned medium (CM) from the 3D model with ECs and
      EPCs promoted network formation compared to CM from an EC monoculture. We also
      confirmed that EPCs secreted vascular endothelial growth factor (VEGF). However,
      networks cultured with the CM were shallow and did not penetrate the collagen gel
      in great depth. Therefore, we conclude that EPCs contribute to 3D network
      formation at least through indirect incorporation by generating a local VEGF
      gradient. These results suggest that the location of EPCs is important for
      controlling directional 3D network formation in the field of tissue engineering. 

PMID- 24312631
TI  - Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and
      differentiation of human subcutaneous adipocytes.
AB  - Stress of endoplasmic reticulum (ERS) is one of the molecular triggers of
      adipocyte dysfunction and chronic low inflammation accompanying obesity. ERS can
      be alleviated by chemical chaperones from the family of bile acids (BAs). Thus,
      two BAs currently used to treat cholestasis, ursodeoxycholic and
      tauroursodeoxycholic acid (UDCA and TUDCA), could potentially lessen adverse
      metabolic effects of obesity. Nevertheless, BAs effects on human adipose cells
      are mostly unknown. They could regulate gene expression through pathways
      different from their chaperone function, namely through activation of farnesoid X
      receptor (FXR) and TGR5, G-coupled receptor. Therefore, this study aimed to
      analyze effects of UDCA and TUDCA on human preadipocytes and differentiated
      adipocytes derived from paired samples of two distinct subcutaneous adipose
      tissue depots, abdominal and gluteal. While TUDCA did not alter proliferation of
      cells from either depot, UDCA exerted strong anti-proliferative effect. In
      differentiated adipocytes, acute exposition to neither TUDCA nor UDCA was able to
      reduce effect of ERS stressor tunicamycin. However, exposure of cells to UDCA
      during whole differentiation process decreased expression of ERS markers. At the
      same time however, UDCA profoundly inhibited adipogenic conversion of cells. UDCA
      abolished expression of PPARgamma and lipogenic enzymes already in the early
      phases of adipogenesis. This anti-adipogenic effect of UDCA was not dependent on
      FXR or TGR5 activation, but could be related to ability of UDCA to sustain the
      activation of ERK1/2 previously linked with PPARgamma inactivation. Finally,
      neither BAs did lower expression of chemokines inducible by TLR4 pathway, when
      UDCA enhanced their expression in gluteal adipocytes. Therefore while TUDCA has
      neutral effect on human preadipocytes and adipocytes, the therapeutic use of UDCA
      different from treating cholestatic diseases should be considered with caution
      because UDCA alters functions of human adipose cells. 

PMID- 24312633
TI  - Residential exposure to 50 Hz magnetic fields and the association with
      miscarriage risk: a 2-year prospective cohort study.
AB  - OBJECTIVE: The hypothesis of whether exposure to extremely low-frequency magnetic
      fields (ELF-MF) may increase miscarriage risk is controversial. A 2-year
      prospective cohort study was designed to study the association between exposure
      to 50 Hz magnetic fields (MF) and the miscarriage risk for women residing in the
      area of the Pearl-River Delta of China. METHOD: Two towns with densely
      distributed power supply constructions were selected as the study sites. From
      2010 to 2012, 552 women in the region who were at approximately 8 weeks of
      gestation or who planned to have a baby within 1 year were selected as candidate
      subjects. Exposure to MF was estimated by measurements at their front doors and
      in the alley in front of the subjects' houses. The average exposure level was
      used as a cutoff point to define the exposed group. Clinical miscarriage was
      diagnosed by local obstetricians. Staffs from the local population and family
      planning service stations were responsible for the follow-up interviews every 2
      months. RESULTS: Four hundred and thirteen pregnant women were selected for the
      cohort study. The average residential exposure to MF was 0.099 uT. No
      significantly increased risk of miscarriage was found to be associated with the
      average front-door exposure (p>0.05). However, miscarriage risk was found to be
      significantly associated with maximum alley exposure (p=0.001). The relative risk
      (RR) of miscarriage from maximum alley exposure was 2.35 (95% C.I.: 1.18-4.71).
      In addition, Cox regression analysis showed that the adjusted hazard ratio of
      maximum alley exposure for miscarriage was 1.72 (95% C.I.:1.10-2.69). CONCLUSION:
      Although the miscarriage incidence was shown to be positively associated with the
      maximum alley MF exposure, the association between miscarriage risk and the
      exposure to MF was not confirmed in the study. The results of this study are of
      interest concerning MF exposure assessment and pregnancy outcomes.

PMID- 24312632
TI  - Inhibition of mitochondrial complex III blocks neuronal differentiation and
      maintains embryonic stem cell pluripotency.
AB  - The mitochondrion is emerging as a key organelle in stem cell biology, acting as
      a regulator of stem cell pluripotency and differentiation. In this study we
      sought to understand the effect of mitochondrial complex III inhibition during
      neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin
      A, a specific complex III inhibitor, embryonic stem cells failed to differentiate
      into dopaminergic neurons, maintaining high Oct4 levels even when subjected to a
      specific differentiation protocol. Mitochondrial inhibition affected distinct
      populations of cells present in culture, inducing cell loss in differentiated
      cells, but not inducing apoptosis in mouse embryonic stem cells. A reduction in
      overall proliferation rate was observed, corresponding to a slight arrest in S
      phase. Moreover, antimycin A treatment induced a consistent increase in HIF
      1alpha protein levels. The present work demonstrates that mitochondrial
      metabolism is critical for neuronal differentiation and emphasizes that
      modulation of mitochondrial functions through pharmacological approaches can be
      useful in the context of controlling stem cell maintenance/differentiation. 

PMID- 24312634
TI  - TAL effector specificity for base 0 of the DNA target is altered in a complex,
      effector- and assay-dependent manner by substitutions for the tryptophan in
      cryptic repeat -1.
AB  - TAL effectors are re-targetable transcription factors used for tailored gene
      regulation and, as TAL effector-nuclease fusions (TALENs), for genome
      engineering. Their hallmark feature is a customizable central string of
      polymorphic amino acid repeats that interact one-to-one with individual DNA bases
      to specify the target. Sequences targeted by TAL effector repeats in nature are
      nearly all directly preceded by a thymine (T) that is required for maximal
      activity, and target sites for custom TAL effector constructs have typically been
      selected with this constraint. Multiple crystal structures suggest that this
      requirement for T at base 0 is encoded by a tryptophan residue (W232) in a
      cryptic repeat N-terminal to the central repeats that exhibits energetically
      favorable van der Waals contacts with the T. We generated variants based on TAL
      effector PthXo1 with all single amino acid substitutions for W232. In a
      transcriptional activation assay, many substitutions altered or relaxed the
      specificity for T and a few were as active as wild type. Some showed higher
      activity. However, when replicated in a different TAL effector, the effects of
      the substitutions differed. Further, the effects differed when tested in the
      context of a TALEN in a DNA cleavage assay, and in a TAL effector-DNA binding
      assay. Substitution of the N-terminal region of the PthXo1 construct with that of
      one of the TAL effector-like proteins of Ralstonia solanacearum, which have
      arginine in place of the tryptophan, resulted in specificity for guanine as the
      5' base but low activity, and several substitutions for the arginine, including
      tryptophan, destroyed activity altogether. Thus, the effects on specificity and
      activity generated by substitutions at the W232 (or equivalent) position are
      complex and context dependent. Generating TAL effector scaffolds with high
      activity that robustly accommodate sites without a T at position 0 may require
      larger scale re-engineering. 

PMID- 24312635
TI  - Lysophosphatidic acid enhances stromal cell-directed angiogenesis.
AB  - Ischemic diseases such as peripheral vascular disease (PVD) affect more than 15%
      of the general population and in severe cases result in ulcers, necrosis, and
      limb loss. While the therapeutic delivery of growth factors to promote
      angiogenesis has been widely investigated, large-scale implementation is limited
      by strategies to effectively deliver costly recombinant proteins. Multipotent
      adipose-derived stromal cells (ASC) and progenitor cells from other tissue
      compartments secrete bioactive concentrations of angiogenic molecules, making
      cell-based strategies for in situ delivery of angiogenic cytokines an exciting
      alternative to the use of recombinant proteins. Here, we show that the
      phospholipid lysophosphatidic acid (LPA) synergistically improves the
      proangiogenic effects of ASC in ischemia. We found that LPA upregulates
      angiogenic growth factor production by ASC under two- and three-dimensional in
      vitro models of serum deprivation and hypoxia (SD/H), and that these factors
      significantly enhance endothelial cell migration. The concurrent delivery of LPA
      and ASC in fibrin gels significantly improves vascularization in a murine
      critical hindlimb ischemia model compared to LPA or ASC alone, thus exhibiting
      the translational potential of this method. Furthermore, these results are
      achieved using an inexpensive lipid molecule, which is orders-of-magnitude less
      costly than recombinant growth factors that are under investigation for similar
      use. Our results demonstrate a novel strategy for enhancing cell-based strategies
      for therapeutic angiogenesis, with significant applications for treating ischemic
      diseases. 

PMID- 24312636
TI  - Synergistic interactions between Alzheimer's Abeta40 and Abeta42 on the surface
      of primary neurons revealed by single molecule microscopy.
AB  - Two amyloid-beta peptides (Abeta40 and Abeta42) feature prominently in the
      extracellular brain deposits associated with Alzheimer's disease. While Abeta40
      is the prevalent form in the cerebrospinal fluid, the fraction of Abeta42
      increases in the amyloid deposits over the course of disease development. The low
      in vivo concentration (pM-nM) and metastable nature of Abeta oligomers have made
      identification of their size, composition, cellular binding sites and mechanism
      of action challenging and elusive. Furthermore, recent studies have suggested
      that synergistic effects between Abeta40 and Abeta42 alter both the formation and
      stability of various peptide oligomers as well as their cytotoxicity. These
      studies often utilized Abeta oligomers that were prepared in solution and at MUM
      peptide concentrations. The current work was performed using physiological Abeta
      concentrations and single-molecule microscopy to follow peptide binding and
      association on primary cultured neurons. When the cells were exposed to a 1:1
      mixture of nM Abeta40:Abeta42, significantly larger membrane-bound oligomers
      developed compared to those formed from either peptide alone. Fluorescence
      resonance energy transfer experiments at the single molecule level reveal that
      these larger oligomers contained both Abeta40 and Abeta42, but that the growth of
      these oligomers was predominantly by addition of Abeta42. Both pure peptides form
      very few oligomers larger than dimers, but either membrane bound Abeta40/42
      complex, or Abeta40, bind Abeta42 to form increasingly larger oligomers. These
      findings may explain how Abeta42-dominant oligomers, suspected of being more
      cytotoxic, develop on the neuronal membrane under physiological conditions. 

PMID- 24312637
TI  - A machine learned classifier that uses gene expression data to accurately predict
      estrogen receptor status.
AB  - BACKGROUND: Selecting the appropriate treatment for breast cancer requires
      accurately determining the estrogen receptor (ER) status of the tumor. However,
      the standard for determining this status, immunohistochemical analysis of
      formalin-fixed paraffin embedded samples, suffers from numerous technical and
      reproducibility issues. Assessment of ER-status based on RNA expression can
      provide more objective, quantitative and reproducible test results. METHODS: To
      learn a parsimonious RNA-based classifier of hormone receptor status, we applied
      a machine learning tool to a training dataset of gene expression microarray data
      obtained from 176 frozen breast tumors, whose ER-status was determined by
      applying ASCO-CAP guidelines to standardized immunohistochemical testing of
      formalin fixed tumor. RESULTS: This produced a three-gene classifier that can
      predict the ER-status of a novel tumor, with a cross-validation accuracy of
      93.17+/-2.44%. When applied to an independent validation set and to four other
      public databases, some on different platforms, this classifier obtained over 90%
      accuracy in each. In addition, we found that this prediction rule separated the
      patients' recurrence-free survival curves with a hazard ratio lower than the one
      based on the IHC analysis of ER-status. CONCLUSIONS: Our efficient and
      parsimonious classifier lends itself to high throughput, highly accurate and low
      cost RNA-based assessments of ER-status, suitable for routine high-throughput
      clinical use. This analytic method provides a proof-of-principle that may be
      applicable to developing effective RNA-based tests for other biomarkers and
      conditions.

PMID- 24312638
TI  - Investigation of a new electrode array technology for a central auditory
      prosthesis.
AB  - Ongoing clinical studies on patients recently implanted with the auditory
      midbrain implant (AMI) into the inferior colliculus (IC) for hearing restoration
      have shown that these patients do not achieve performance levels comparable to
      cochlear implant patients. The AMI consists of a single-shank array (20
      electrodes) for stimulation along the tonotopic axis of the IC. Recent findings
      suggest that one major limitation in AMI performance is the inability to
      sufficiently activate neurons across the three-dimensional (3-D) IC.
      Unfortunately, there are no currently available 3-D array technologies that can
      be used for clinical applications. More recently, there has been a new initiative
      by the European Commission to fund and develop 3-D chronic electrode arrays for
      science and clinical applications through the NeuroProbes project that can
      overcome the bulkiness and limited 3-D configurations of currently available
      array technologies. As part of the NeuroProbes initiative, we investigated
      whether their new array technology could be potentially used for future AMI
      patients. Since the NeuroProbes technology had not yet been tested for electrical
      stimulation in an in vivo animal preparation, we performed experiments in
      ketamine-anesthetized guinea pigs in which we inserted and stimulated a
      NeuroProbes array within the IC and recorded the corresponding neural activation
      within the auditory cortex. We used 2-D arrays for this initial feasibility study
      since they were already available and were sufficient to access the IC and also
      demonstrate effective activation of the central auditory system. Based on these
      encouraging results and the ability to develop customized 3-D arrays with the
      NeuroProbes technology, we can further investigate different stimulation patterns
      across the ICC to improve AMI performance. 

PMID- 24312639
TI  - Transcriptome analysis of Portunus trituberculatus in response to salinity stress
      provides insights into the molecular basis of osmoregulation.
AB  - BACKGROUND: The swimming crab, Portunus trituberculatus, which is naturally
      distributed in the coastal waters of Asia-Pacific countries, is an important
      farmed species in China. Salinity is one of the most important abiotic factors
      that influence not only the distribution and abundance of crustaceans, it is also
      an important factor for artificial propagation of the crab. To better understand
      the interaction between salinity stress and osmoregulation, we performed a
      transcriptome analysis in the gills of Portunus trituberculatus challenged with
      salinity stress, using the Illumina Deep Sequencing technology. RESULTS: We
      obtained 27,696,835, 28,268,353 and 33,901,271 qualified Illumina read pairs from
      low salinity challenged (LC), non-challenged (NC), and high salinity challenged
      (HC) Portunus trituberculatus cDNA libraries, respectively. The overall de novo
      assembly of cDNA sequence data generated 94,511 unigenes, with an average length
      of 644 bp. Comparative genomic analysis revealed that 1,705 genes differentially
      expressed in salinity stress compared to the controls, including 615 and 1,516
      unigenes in NC vs LC and NC vs HC respectively. GO functional enrichment analysis
      results showed some differentially expressed genes were involved in crucial
      processes related to osmoregulation, such as ion transport processes, amino acid
      metabolism and synthesis processes, proteolysis process and chitin metabolic
      process. CONCLUSION: This work represents the first report of the utilization of
      the next generation sequencing techniques for transcriptome analysis in Portunus
      trituberculatus and provides valuable information on salinity adaptation
      mechanism. Results reveal a substantial number of genes modified by salinity
      stress and a few important salinity acclimation pathways, which will serve as an
      invaluable resource for revealing the molecular basis of osmoregulation in
      Portunus trituberculatus. In addition, the most comprehensive sequences of
      transcripts reported in this study provide a rich source for identification of
      novel genes in the crab.

PMID- 24312640
TI  - Concordance between phylogeographical and biogeographical patterns in the
      Brazilian Cerrado: diversification of the endemic tree Dalbergia miscolobium
      (Fabaceae).
AB  - Few studies have addressed the phylogeography of species of the Cerrado, the
      largest savanna biome of South America. Here we aimed to investigate the
      phylogeographical structure of Dalbergia miscolobium, a widespread tree from the
      Cerrado, and to verify its concordance with plant phylogeographical and
      biogeographical patterns so far described. A total of 287 individuals from 32
      populations were analyzed by sequencing the trnL intron of the chloroplast DNA
      and the internal transcribed spacer of the nuclear ribosomal DNA. Analysis of
      population structure and tests of population expansion were performed and the
      time of divergence of haplotypes was estimated. Twelve and 27 haplotypes were
      identified in the cpDNA and nrDNA data, respectively. The star-like network
      configuration and the mismatch distributions indicated a recent spatial and
      demographic expansion of the species. Consistent with previous tree
      phylogeographical studies of Cerrado trees, the cpDNA also suggested a recent
      expansion towards the southern Cerrado. The diversity of D. miscolobium was
      widespread but high levels of genetic diversity were found in the Central Eastern
      and in the southern portion of Central Western Cerrado. The combined analysis of
      cpDNA and nrDNA supported a phylogeographic structure into seven groups. The
      phylogeographical pattern showed many concordances with biogeographical and
      phylogeographical studies in the Cerrado, mainly with the Cerrado phytogeographic
      provinces superimposed to our sampling area. The data reinforced the uniqueness
      of Northeastern and Southeastern Cerrados and the differentiation between Eastern
      and Western Central Cerrados. The recent diversification of the species
      (estimated between the Pliocene and the Pleistocene) and the 'genealogical
      concordances' suggest that a shared and persistent pattern of species
      diversification might have been present in the Cerrado over time. This is the
      first time that an extensive 'genealogical concordance' between phylogeographic
      and phytogeographic patterns is shown for the Cerrado biome. 

PMID- 24312641
TI  - Rhein, a natural anthraquinone derivative, attenuates the activation of
      pancreatic stellate cells and ameliorates pancreatic fibrosis in mice with
      experimental chronic pancreatitis.
AB  - Pancreatic fibrosis, a prominent histopathological feature of chronic
      pancreatitis (CP) and pancreatic ductal adenocarcinoma, is essentially a dynamic
      process that leads to irreversible scarring of parenchymal tissues of the
      pancreas. Though the exact mechanisms of its initiation and development are
      poorly understood, recent studies suggested that the activation of pancreatic
      stellate cells (PSCs) plays a critical role in eliciting such active course of
      fibrogenesis. Anthraquinone compounds possess anti-inflammatory bioactivities
      whereas its natural derivative rhein has been shown to effectively reduce tissue
      edema and free-radical production in rat models of inflammatory conditions. Apart
      from its anti-inflammatory properties, rhein actually exerts strong anti-fibrotic
      effects in our current in-vivo and in-vitro experiments. In the mouse model of
      cerulein-induced CP, prolonged administration of rhein at 50 mg/kg/day
      significantly decreased immunoreactivities of the principal fibrotic activators
      alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta (TGF
      beta) on pancreatic sections implicating the activation of PSCs, which is the
      central tread to fibrogenesis, was attenuated. Consequently, the overwhelmed
      deposition of extracellular matrix proteins fibronectin 1 (FN1) and type I
      collagen (COL I-alpha1) in exocrine parenchyma was found accordingly reduced. In
      addition, the expression levels of sonic hedgehog (SHH), which plays important
      roles in molecular modulation of various fibrotic processes, and its immediate
      effector GLI1 in pancreatic tissues were positively correlated to the degree of
      cerulein-induced fibrosis. Such up-regulation of SHH signaling was restrained in
      rhein-treated CP mice. In cultured PSCs, we demonstrated that the expression
      levels of TGF-beta-stimulated fibrogenic markers including alpha-SMA, FN1 and COL
      I-alpha1 as well as SHH were all notably suppressed by the application of rhein
      at 10 MUM. The present study firstly reported that rhein attenuates PSC
      activation and suppresses SHH/GLI1 signaling in pancreatic fibrosis. With strong
      anti-fibrotic effects provided, rhein can be a potential remedy for fibrotic
      and/or PSC-related pathologies in the pancreas. 

PMID- 24312642
TI  - ICOS regulates the generation and function of human CD4+ Treg in a CTLA-4
      dependent manner.
AB  - Inducible co-stimulator (ICOS) is a member of CD28/Cytotoxic T-lymphocyte Antigen
      4 (CTLA-4) family and broadly expressed in activated CD4(+) T cells and induced
      regulatory CD4(+) T cells (CD4(+) iTreg). ICOS-related signal pathway could be
      activated by the interaction between ICOS and its ligand (ICOSL). In our previous
      work, we established a cost-effective system to generate a novel human allo
      antigen specific CD4(hi) Treg by co-culturing their naive precursors with
      allogeneic CD40-activated B cells in vitro. Here we investigate the role of ICOS
      in the generation and function of CD4(hi) Treg by interrupting ICOS-ICOSL
      interaction with ICOS-Ig. It is found that blockade of ICOS-ICOSL interaction
      impairs the induction and expansion of CD4(hi) Treg induced by allogeneic CD40
      activated B cells. More importantly, CD4(hi) Treg induced with the addition of
      ICOS-Ig exhibits decreased suppressive capacity on alloantigen-specific
      responses. Dysfunction of CD4(hi) Treg induced with ICOS-Ig is accompanied with
      its decreased exocytosis and surface CTLA-4 expression. Through inhibiting
      endocytosis with E64 and pepstatin A, surface CTLA-4 expression and suppressive
      functions of induced CD4(hi) Treg could be partly reversed. Conclusively, our
      results demonstrate the beneficial role of ICOS-ICOSL signal pathway in the
      generation and function of CD4(hi) Treg and uncover a novel relationship between
      ICOS and CTLA-4. 

PMID- 24312643
TI  - Flexibility within the rotor and stators of the vacuolar H+-ATPase.
AB  - The V-ATPase is a membrane-bound protein complex which pumps protons across the
      membrane to generate a large proton motive force through the coupling of an ATP
      driven 3-stroke rotary motor (V1) to a multistroke proton pump (Vo). This is done
      with near 100% efficiency, which is achieved in part by flexibility within the
      central rotor axle and stator connections, allowing the system to flex to
      minimise the free energy loss of conformational changes during catalysis. We have
      used electron microscopy to reveal distinctive bending along the V-ATPase
      complex, leading to angular displacement of the V1 domain relative to the Vo
      domain to a maximum of ~30 degrees . This has been complemented by elastic
      network normal mode analysis that shows both flexing and twisting with the
      compliance being located in the rotor axle, stator filaments, or both. This study
      provides direct evidence of flexibility within the V-ATPase and by implication in
      related rotary ATPases, a feature predicted to be important for regulation and
      their high energetic efficiencies. 

PMID- 24312645
TI  - Blood-borne hepatitis in opiate users in iran: a poor outlook and urgent need to
      change nationwide screening policy.
AB  - OBJECTIVE: Iran has the highest rate of opiate use worldwide. However, most
      opiate users are not screened for hepatitis virus infections. This study aimed to
      provide accurate, detailed data on the size of the opiate user population at risk
      of developing these infections. METHOD: This seroprevalence study was conducted
      in the city of Shiraz, southern Iran. All participants were screened for HBV, HCV
      and HIV infection. The data were analyzed with SPSS. RESULT: Among 569
      participants, 233 (40.9%) were injection drug users (IDU), 369 (64.8%) were
      heterosexual, 84 (14.7%) were bisexual and 15 (2.6%) were homosexual. One hundred
      nine (19.1%) were HCV antibody-positive, 18 (3.1%) were HBS antigen-positive, 72
      (12.6%) were HBc antibody-positive and 23 (4%) were HIV-positive. Among IDU
      compared to non-IDU, positivity rates for HBS antigen (5.5 vs 1.4%), HBc antibody
      (22.7 vs 5.6%), HCV antibody (40.3 vs 4.4%) and HIV (7.7 vs 1.4%) were higher (P
      < 0.05). Most patients with HBV (80.7%) and HCV infection (83.4%) were HIV
      negative. In the cumulative analysis, only history of imprisonment was a
      statistically significant determinant of infection by HCV or HBV in opiate users.
      CONCLUSION: The current policy of screening only HIV-positive drug users for HBV
      and HCV in Iran misses most cases of HBV and HCV infection. We therefore
      recommend urgent revision of the nationwide protocol by the Ministry of Health in
      Iran to implement routine screening of all opiate users and especially IDU for
      these viruses, regardless of their HIV status.

PMID- 24312644
TI  - C11ORF24 is a novel type I membrane protein that cycles between the Golgi
      apparatus and the plasma membrane in Rab6-positive vesicles.
AB  - The Golgi apparatus is an intracellular compartment necessary for post
      translational modification, sorting and transport of proteins. It plays a key
      role in mitotic entry through the Golgi mitotic checkpoint. In order to identify
      new proteins involved in the Golgi mitotic checkpoint, we combine the results of
      a knockdown screen for mitotic phenotypes and a localization screen. Using this
      approach, we identify a new Golgi protein C11ORF24 (NP_071733.1). We show that
      C11ORF24 has a signal peptide at the N-terminus and a transmembrane domain in the
      C-terminal region. C11ORF24 is localized on the Golgi apparatus and on the trans
      Golgi network. A large part of the protein is present in the lumen of the Golgi
      apparatus whereas only a short tail extends into the cytosol. This cytosolic tail
      is well conserved in evolution. By FRAP experiments we show that the dynamics of
      C11ORF24 in the Golgi membrane are coherent with the presence of a transmembrane
      domain in the protein. C11ORF24 is not only present on the Golgi apparatus but
      also cycles to the plasma membrane via endosomes in a pH sensitive manner.
      Moreover, via video-microscopy studies we show that C11ORF24 is found on
      transport intermediates and is colocalized with the small GTPase RAB6, a GTPase
      involved in anterograde transport from the Golgi to the plasma membrane. Knocking
      down C11ORF24 does not lead to a mitotic phenotype or an intracellular transport
      defect in our hands. All together, these data suggest that C11ORF24 is present on
      the Golgi apparatus, transported to the plasma membrane and cycles back through
      the endosomes by way of RAB6 positive carriers. 

PMID- 24312646
TI  - Preference and prey switching in a generalist predator attacking local and
      invasive alien pests.
AB  - Invasive pest species may strongly affect biotic interactions in agro-ecosystems.
      The ability of generalist predators to prey on new invasive pests may result in
      drastic changes in the population dynamics of local pest species owing to
      predator-mediated indirect interactions among prey. On a short time scale, the
      nature and strength of such indirect interactions depend largely on preferences
      between prey and on predator behavior patterns. Under laboratory conditions we
      evaluated the prey preference of the generalist predator Macrolophus pygmaeus
      Rambur (Heteroptera: Miridae) when it encounters simultaneously the local tomato
      pest Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) and the invasive alien
      pest Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). We tested various ratios
      of local vs. alien prey numbers, measuring switching by the predator from one
      prey to the other, and assessing what conditions (e.g. prey species abundance and
      prey development stage) may favor such prey switching. The total predation
      activity of M. pygmaeus was affected by the presence of T. absoluta in the prey
      complex with an opposite effect when comparing adult and juvenile predators. The
      predator showed similar preference toward T. absoluta eggs and B. tabaci nymphs,
      but T. absoluta larvae were clearly less attacked. However, prey preference
      strongly depended on prey relative abundance with a disproportionately high
      predation on the most abundant prey and disproportionately low predation on the
      rarest prey. Together with the findings of a recent companion study (Bompard et
      al. 2013, Population Ecology), the insight obtained on M. pygmaeus prey switching
      may be useful for Integrated Pest Management in tomato crops, notably for optimal
      simultaneous management of B. tabaci and T. absoluta, which very frequently co
      occur on tomato. 

PMID- 24312647
TI  - LPS exposure increases maternal corticosterone levels, causes placental injury
      and increases IL-1Beta levels in adult rat offspring: relevance to autism.
AB  - Maternal immune activation can induce neuropsychiatric disorders, such as autism
      and schizophrenia. Previous investigations by our group have shown that prenatal
      treatment of rats on gestation day 9.5 with lipopolysaccharide (LPS; 100 MUg/kg,
      intraperitoneally), which mimics infections by gram-negative bacteria, induced
      autism-like behavior in male rats, including impaired communication and
      socialization and induced repetitive/restricted behavior. However, the behavior
      of female rats was unchanged. Little is known about how LPS-induced changes in
      the pregnant dam subsequently affect the developing fetus and the fetal immune
      system. The present study evaluated the hypothalamic-pituitary-adrenal (HPA) axis
      activity, the placental tissue and the reproductive performance of pregnant
      Wistar rats exposed to LPS. In the adult offspring, we evaluated the HPA axis and
      pro-inflammatory cytokine levels with or without a LPS challenge. LPS exposure
      increased maternal serum corticosterone levels, injured placental tissue and led
      to higher post-implantation loss, resulting in fewer live fetuses. The HPA axis
      was not affected in adult offspring. However, prenatal LPS exposure increased IL
      1beta serum levels, revealing that prenatal LPS exposure modified the immune
      response to a LPS challenge in adulthood. Increased IL-1beta levels have been
      reported in several autistic patients. Together with our previous studies, our
      model induced autistic-like behavioral and immune disturbances in childhood and
      adulthood, indicating that it is a robust rat model of autism. 

PMID- 24312648
TI  - Glasgow Coma Scale and outcomes after structural traumatic head injury in early
      childhood.
AB  - OBJECTIVE: To assess the association of the Glasgow Coma Scale (GCS) with
      radiological evidence of head injury (the Abbreviated Injury Scale for the head
      region, AIS-HR) in young children hospitalized with traumatic head injury (THI),
      and the predictive value of GCS and AIS-HR scores for long-term impairment.
      METHODS: Our study involved a 10-year retrospective review of a database
      encompassing all patients admitted to Starship Children's Hospital (Auckland, New
      Zealand, 2000-2010) with THI. RESULTS: We studied 619 children aged <5 years at
      the time of THI, with long-term outcome data available for 161 subjects. Both GCS
      and AIS-HR scores were predictive of length of intensive care unit and hospital
      stay (all p<0.001). GCS was correlated with AIS-HR (rho=-0.46; p<0.001), although
      mild GCS scores (13-15) commonly under-estimated the severity of radiological
      injury: 42% of children with mild GCS scores had serious-critical THI (AIS-HR 3
      5). Increasingly severe GCS or AIS-HR scores were both associated with a greater
      likelihood of long-term impairment (neurological disability, residual problems,
      and educational support). However, long-term impairment was also relatively
      common in children with mild GCS scores paired with structural THI more severe
      than a simple linear skull fracture. CONCLUSION: Severe GCS scores will identify
      most cases of severe radiological injury in early childhood, and are good
      predictors of poor long-term outcome. However, young children admitted to
      hospital with structural THI and mild GCS scores have an appreciable risk of long
      term disability, and also warrant long-term follow-up.

PMID- 24312649
TI  - Protein microarray analysis of antibody responses to Plasmodium falciparum in
      western Kenyan highland sites with differing transmission levels.
AB  - Malaria represents a major public health problem in Africa. In the East African
      highlands, the high-altitude areas were previously considered too cold to support
      vector population and parasite transmission, rendering the region particularly
      prone to epidemic malaria due to the lack of protective immunity of the
      population. Since the 1980's, frequent malaria epidemics have been reported and
      these successive outbreaks may have generated some immunity against Plasmodium
      falciparum amongst the highland residents. Serological studies reveal indirect
      evidence of human exposure to the parasite, and can reliably assess prevalence of
      exposure and transmission intensity in an endemic area. However, the vast
      majority of serological studies of malaria have been, hereto, limited to a small
      number of the parasite's antigens. We surveyed and compared the antibody response
      profiles of age-stratified sera from residents of two endemic areas in the
      western Kenyan highlands with differing malaria transmission intensities, during
      two distinct seasons, against 854 polypeptides of P. falciparum using high
      throughput proteomic microarray technology. We identified 107 proteins as serum
      antibody targets, which were then characterized for their gene ontology
      biological process and cellular component of the parasite, and showed significant
      enrichment for categories related to immune evasion, pathogenesis and expression
      on the host's cell and parasite's surface. Additionally, we calculated age-fitted
      annual seroconversion rates for the immunogenic proteins, and contrasted the age
      dependent antibody acquisition for those antigens between the two sampling sites.
      We observed highly immunogenic antigens that produce stable antibody responses
      from early age in both sites, as well as less immunogenic proteins that require
      repeated exposure for stable responses to develop and produce different
      seroconversion rates between sites. We propose that a combination of highly and
      less immunogenic proteins could be used in serological surveys to detect
      differences in malaria transmission levels, distinguishing sites of unstable and
      stable transmission. 

PMID- 24312650
TI  - Aetiology of pulmonary symptoms in HIV-infected smear negative recurrent PTB
      suspects in Kampala, Uganda: a cross-sectional study.
AB  - INTRODUCTION: Previously treated TB patients with pulmonary symptoms are often
      considered recurrent TB suspects in the resource-limited settings, where
      investigations are limited to microscopy and chest x-ray. Category II anti-TB
      drugs may be inappropriate and may expose patients to pill burden, drug
      toxicities and drug-drug interactions. OBJECTIVE: To determine the causes of
      pulmonary symptoms in HIV-infected smear negative recurrent pulmonary
      tuberculosis suspects at Mulago Hospital, Kampala. METHODS: Between March 2008
      and December 2011, induced sputum samples of 178 consented HIV-infected smear
      negative recurrent TB suspects in Kampala were subjected to MGIT and LJ cultures
      for mycobacteria at TB Reference Laboratory, Kampala. Processed sputum samples
      were also tested by PCR to detect 18S rRNA gene of P.jirovecii and cultured for
      other bacteria. RESULTS: Bacteria, M. tuberculosis and Pneumocystis jirovecii
      were detected in 27%, 18% and 6.7% of patients respectively and 53.4% of the
      specimens had no microorganisms. S. pneumoniae, M. catarrhalis and H. influenzae
      were 100% susceptible to chloramphenicol and erythromycin but co-trimoxazole
      resistant. CONCLUSION: At least 81.5% of participants had no microbiologically
      confirmed TB. However our findings call for thorough investigation of HIV
      infected smear negative recurrent TB suspects to guide cost effective treatment.

PMID- 24312651
TI  - Chikungunya as a cause of acute febrile illness in southern Sri Lanka.
AB  - BACKGROUND: Chikungunya virus (CHIKV) re-emerged in Sri Lanka in late 2006 after
      a 40-year hiatus. We sought to identify and characterize acute chikungunya
      infection (CHIK) in patients presenting with acute undifferentiated febrile
      illness in unstudied rural and semi-urban southern Sri Lanka in 2007.
      METHODOLOGY/PRINCIPAL FINDINGS: We enrolled febrile patients >= 2 years of age,
      collected uniform epidemiologic and clinical data, and obtained serum samples for
      serology, virus isolation, and real-time reverse-transcriptase PCR (RT-PCR).
      Serology on paired acute and convalescent samples identified acute chikungunya
      infection in 3.5% (28/797) patients without acute dengue virus (DENV) infection,
      64.3% (18/28) of which were confirmed by viral isolation and/or real-time RT-PCR.
      No CHIKV/DENV co-infections were detected among 54 patients with confirmed acute
      DENV. Sequencing of the E1 coding region of six temporally distinct CHIKV
      isolates (April through October 2007) showed that all isolates posessed the E1
      226A residue and were most closely related to Sri Lankan and Indian isolates from
      the same time period. Except for more frequent and persistent musculoskeletal
      symptoms, acute chikungunya infections mimicked DENV and other acute febrile
      illnesses. Only 12/797 (1.5%) patients had serological evidence of past
      chikungunya infection. CONCLUSIONS/SIGNIFICANCE: Our findings suggest CHIKV is a
      prominent cause of non-specific acute febrile illness in southern Sri Lanka.

PMID- 24312652
TI  - Estimation of the fraction of cancer cells in a tumor DNA sample using DNA
      methylation.
AB  - Contamination of normal cells is almost always present in tumor samples and
      affects their molecular analyses. DNA methylation, a stable epigenetic
      modification, is cell type-dependent, and different between cancer and normal
      cells. Here, we aimed to demonstrate that DNA methylation can be used to estimate
      the fraction of cancer cells in a tumor DNA sample, using esophageal squamous
      cell carcinoma (ESCC) as an example. First, by an Infinium HumanMethylation450
      BeadChip array, we isolated three genomic regions (TFAP2B, ARHGEF4, and RAPGEFL1)
      i) highly methylated in four ESCC cell lines, ii) hardly methylated in a pooled
      sample of non-cancerous mucosae, a pooled sample of normal esophageal mucosae,
      and peripheral leukocytes, and iii) frequently methylated in 28 ESCCs (TFAP2B,
      24/28; ARHGEF4, 20/28; and RAPGEFL1, 19/28). Second, using eight pairs of cancer
      and non-cancer cell samples prepared by laser capture microdissection, we
      confirmed that at least one of the three regions was almost completely methylated
      in ESCC cells, and all the three regions were almost completely unmethylated in
      non-cancer cells. We also confirmed that DNA copy number alterations of the three
      regions in 15 ESCC samples were rare, and did not affect the estimation of the
      fraction of cancer cells. Then, the fraction of cancer cells in a tumor DNA
      sample was defined as the highest methylation level of the three regions, and we
      confirmed a high correlation between the fraction assessed by the DNA methylation
      fraction marker and the fraction assessed by a pathologist (r=0.85; p<0.001).
      Finally, we observed that, by correction of the cancer cell content, CpG islands
      in promoter regions of tumor-suppressor genes were almost completely methylated.
      These results demonstrate that DNA methylation can be used to estimate the
      fraction of cancer cells in a tumor DNA sample. 

PMID- 24312653
TI  - Development of a consensus taxonomy of sedentary behaviors (SIT): report of
      Delphi Round 1.
AB  - BACKGROUND: Over the last decade, sedentary behaviors have emerged as a
      distinctive behavioral paradigm with deleterious effects on health independent of
      physical activity. The next phase of research is to establish dose response
      between sedentary behaviors and health outcomes and improve understanding of
      context and determinants of these behaviors. Establishing a common taxonomy of
      these behaviors is a necessary step in this process. AIM: The Sedentary behavior
      International Taxonomy project was developed to establish a classification of
      sedentary behaviors by use of a formal consensus process. METHODS: The study
      follows a Delphi process in three Rounds. A preparatory stage informed the
      development of terms of reference documents. In Round 1, experts were asked to
      make statements about the taxonomy; 1) its purpose and use ; 2) the domains,
      categories or facets that should be consider and include; 3) the
      structure/architecture to arrange and link these domains and facets. In Round 2
      experts will be presented with a draft taxonomy emerging from Round 1 and invited
      to comment and propose alterations. The taxonomy will then be finalised at the
      outset of this stage. RESULTS: Results of Round 1 are reported here. There is a
      general consensus that a taxonomy will help advances in research by facilitating
      systematic and standardised: 1) investigation and analysis; 2) reporting and
      communication; 3) data pooling, comparison and meta-analysis; 4) development of
      measurement tools; 4) data descriptions, leading to higher quality in data
      querying and facilitate discoveries. There is also a consensus that such a
      taxonomy should be flexible to accommodate diverse purposes of use, and future
      advances in the field and yet provide a cross-disciplinary common language. A
      consensual taxonomy structure emerged with nine primary facets (Purpose,
      Environment, Posture, Social, Measurement, Associated behavior, Status, Time,
      Type) and the draft structure presented here for Round 2.

PMID- 24312654
TI  - A daily oscillation in the fundamental frequency and amplitude of harmonic
      syllables of zebra finch song.
AB  - Complex motor skills are more difficult to perform at certain points in the day
      (for example, shortly after waking), but the daily trajectory of motor-skill
      error is more difficult to predict. By undertaking a quantitative analysis of the
      fundamental frequency (FF) and amplitude of hundreds of zebra finch syllables per
      animal per day, we find that zebra finch song follows a previously undescribed
      daily oscillation. The FF and amplitude of harmonic syllables rises across the
      morning, reaching a peak near mid-day, and then falls again in the late afternoon
      until sleep. This oscillation, although somewhat variable, is consistent across
      days and across animals and does not require serotonin, as animals with
      serotonergic lesions maintained daily oscillations. We hypothesize that this
      oscillation is driven by underlying physiological factors which could be shared
      with other taxa. Song production in zebra finches is a model system for studying
      complex learned behavior because of the ease of gathering comprehensive
      behavioral data and the tractability of the underlying neural circuitry. The
      daily oscillation that we describe promises to reveal new insights into how time
      of day affects the ability to accomplish a variety of complex learned motor
      skills. 

PMID- 24312655
TI  - Intercellular redistribution of cAMP underlies selective suppression of cancer
      cell growth by connexin26.
AB  - Connexins (Cx), which constitute gap junction intercellular channels in
      vertebrates, have been shown to suppress transformed cell growth and
      tumorigenesis, but the mechanism(s) still remain largely speculative. Here, we
      define the molecular basis by which Cx26, but less frequently Cx43 or Cx32,
      selectively confer growth suppression on cancer cells. Functional intercellular
      coupling is shown to be required, producing partial blocks of the cell cycle due
      to prolonged activation of several mitogenic kinases. PKA is both necessary and
      sufficient for the Cx26 induced growth inhibition in low serum and the absence of
      anchorage. Activation of PKA was not associated with elevated cAMP levels, but
      appeared to result from a redistribution of cAMP throughout the cell population,
      eliminating the cell cycle oscillations in cAMP required for efficient cell cycle
      progression. Cx43 and Cx32 fail to mediate this redistribution as, unlike Cx26,
      these channels are closed during the G2/M phase of the cell cycle when cAMP
      levels peak. Comparisons of tumor cell lines indicate that this is a general
      pattern, with growth suppression by connexins occurring whenever cAMP oscillates
      with the cell cycle, and the gap junction remain open throughout the cell cycle.
      Thus, gap junctional coupling, in the absence of any external signals, provides a
      general means to limit the mitotic rate of cell populations. 

PMID- 24312656
TI  - Resveratrol attenuates diabetic nephropathy via modulating angiogenesis.
AB  - Angiogenesis plays an important role in the pathogenesis of diabetic nephropathy
      (DN). In the present study, we investigated the therapeutic potential of
      resveratrol, a polyphenol with antiangiogenic activity in DN. In a type 1
      diabetic rat model, resveratrol treatment blunted the increases of urine albumin
      excretion, kidney weight and creatinine clearance rate. The increases of
      glomerular diameter, mesangium accumulation, glomerular basement membrane
      thickness and renal fibrosis in diabetic rats were also reduced by resveratrol
      treatment. In the diabetic kidney, increased expression of vascular endothelial
      growth factor (VEGF), Flk-1 and angiopoietin 2, and reduced expression of Tie-2
      were observed. These changes in angiogenic hormones and associated receptors were
      attenuated by resveratrol treatment. No changes in angiopoietin 1 expression were
      detected among each group of rats. Resveratrol also significantly downregulated
      high glucose-induced VEGF and Flk-1 expressions in cultured mouse glomerular
      podocytes and endothelial cells, respectively. These effects were attenuated by
      knocking-down silent information regulator 1 (Sirt1) expression. In contrast,
      upregulation of Sirt1 in cultured endothelial cells reduced Flk-1 expression.
      Increased permeability and cellular junction disruption of cultured endothelial
      cells caused by VEGF were also inhibited by resveratrol pretreatment. Taken
      together, the present study demonstrated that resveratrol may attenuate DN via
      modulating angiogenesis. 

PMID- 24312657
TI  - The phylogeography and spatiotemporal spread of south-central skunk rabies virus.
AB  - The south-central skunk rabies virus (SCSK) is the most broadly distributed
      terrestrial viral lineage in North America. Skunk rabies has not been efficiently
      targeted by oral vaccination campaigns and represents a natural system of
      pathogen invasion, yielding insights to rabies emergence. In the present study we
      reconstructed spatiotemporal spread of SCSK in the whole territory of its
      circulation using a combination of Bayesian methods. The analysis based on 241
      glycoprotein gene sequences demonstrated that SCSK is much more divergent
      phylogenetically than was appreciated previously. According to our analyses the
      SCSK originated in the territory of Texas ~170 years ago, and spread
      geographically during the following decades. The wavefront velocity in the
      northward direction was significantly greater than in the eastward and westward
      directions. Rivers (except the Mississippi River and Rio Grande River) did not
      constitute significant barriers for epizootic spread, in contrast to deserts and
      mountains. The mean dispersal rate of skunk rabies was lower than that of the
      raccoon and fox rabies. Viral lineages circulate in their areas with limited
      evidence of geographic spread during decades. However, spatiotemporal
      reconstruction shows that after a long period of stability the dispersal rate and
      wavefront velocity of SCSK are increasing. Our results indicate that there is a
      need to develop control measures for SCSK, and suggest how such measure can be
      implemented most efficiently. Our approach can be extrapolated to other rabies
      reservoirs and used as a tool for investigation of epizootic patterns and
      planning interventions towards disease elimination. 

PMID- 24312658
TI  - Pre-clinical development of a recombinant, replication-competent adenovirus
      serotype 4 vector vaccine expressing HIV-1 envelope 1086 clade C.
AB  - BACKGROUND: There is a well-acknowledged need for an effective AIDS vaccine that
      protects against HIV-1 infection or limits in vivo viral replication. The
      objective of these studies is to develop a replication-competent, vaccine vector
      based on the adenovirus serotype 4 (Ad4) virus expressing HIV-1 envelope (Env)
      1086 clade C glycoprotein. Ad4 recombinant vectors expressing Env gp160
      (Ad4Env160), Env gp140 (Ad4Env140), and Env gp120 (Ad4Env120) were evaluated.
      METHODS: The recombinant Ad4 vectors were generated with a full deletion of the
      E3 region of Ad4 to accommodate the env gene sequences. The vaccine candidates
      were assessed in vitro following infection of A549 cells for Env-specific protein
      expression and for posttranslational transport to the cell surface as monitored
      by the binding of broadly neutralizing antibodies (bNAbs). The capacity of the
      Ad4Env vaccines to induce humoral immunity was evaluated in rabbits for Env gp140
      and V1V2-specific binding antibodies, and HIV-1 pseudovirus neutralization. Mice
      immunized with the Ad4Env160 vaccine were assessed for IFNgamma T cell responses
      specific for overlapping Env peptide sets. RESULTS: Robust Env protein expression
      was confirmed by western blot analysis and recognition of cell surface Env gp160
      by multiple bNAbs. Ad4Env vaccines induced humoral immune responses in rabbits
      that recognized Env 1086 gp140 and V1V2 polypeptide sequences derived from 1086
      clade C, A244 clade AE, and gp70 V1V2 CASE A2 clade B fusion protein. The immune
      sera efficiently neutralized tier 1 clade C pseudovirus MW965.26 and neutralized
      the homologous and heterologous tier 2 pseudoviruses to a lesser extent. Env
      specific T cell responses were also induced in mice following Ad4Env160 vector
      immunization. CONCLUSIONS: The Ad4Env vaccine vectors express high levels of Env
      glycoprotein and induce both Env-specific humoral and cellular immunity thus
      supporting further development of this new Ad4 HIV-1 Env vaccine platform in
      Phase 1 clinical trials.

PMID- 24312659
TI  - A probabilistic model for reducing medication errors.
AB  - BACKGROUND: Medication errors are common, life threatening, costly but
      preventable. Information technology and automated systems are highly efficient
      for preventing medication errors and therefore widely employed in hospital
      settings. The aim of this study was to construct a probabilistic model that can
      reduce medication errors by identifying uncommon or rare associations between
      medications and diseases. METHODS AND FINDINGS: Association rules of mining
      techniques are utilized for 103.5 million prescriptions from Taiwan's National
      Health Insurance database. The dataset included 204.5 million diagnoses with ICD9
      CM codes and 347.7 million medications by using ATC codes. Disease-Medication
      (DM) and Medication-Medication (MM) associations were computed by their co
      occurrence and associations' strength were measured by the interestingness or
      lift values which were being referred as Q values. The DMQs and MMQs were used to
      develop the AOP model to predict the appropriateness of a given prescription.
      Validation of this model was done by comparing the results of evaluation
      performed by the AOP model and verified by human experts. The results showed 96%
      accuracy for appropriate and 45% accuracy for inappropriate prescriptions, with a
      sensitivity and specificity of 75.9% and 89.5%, respectively. CONCLUSIONS: We
      successfully developed the AOP model as an efficient tool for automatic
      identification of uncommon or rare associations between disease-medication and
      medication-medication in prescriptions. The AOP model helps to reduce medication
      errors by alerting physicians, improving the patients' safety and the overall
      quality of care.

PMID- 24312660
TI  - Evolutionary history of the GABA transporter (GAT) group revealed by marine
      invertebrate GAT-1.
AB  - The GABA transporter (GAT) group is one of the major subgroups in the solute
      career 6 (SLC6) family of transmembrane proteins. The GAT group, which has been
      well studied in mammals, has 6 known members, i.e., a taurine transporter (TAUT),
      four GABA transporters (GAT-1, -2, -3, - 4), and a creatine transporter (CT1),
      which have important roles in maintaining physiological homeostasis. However, the
      GAT group has not been extensively investigated in invertebrates; only TAUT has
      been reported in marine invertebrates such as bivalves and krills, and GAT-1 has
      been reported in several insect species and nematodes. Thus, it is unknown how
      transporters in the GAT group arose during the course of animal evolution. In
      this study, we cloned GAT-1 cDNAs from the deep-sea mussel, Bathymodiolus
      septemdierum, and the Antarctic krill, Euphausia superba, whose TAUT cDNA has
      already been cloned. To understand the evolutionary history of the GAT group, we
      conducted phylogenetic and synteny analyses on the GAT group transporters of
      vertebrates and invertebrates. Our findings suggest that transporters of the GAT
      group evolved through the following processes. First, GAT-1 and CT1 arose by
      tandem duplication of an ancestral transporter gene before the divergence of
      Deuterostomia and Protostomia; next, the TAUT gene arose and GAT-3 was formed by
      the tandem duplication of the TAUT gene; and finally, GAT-2 and GAT-4 evolved
      from a GAT-3 gene by chromosomal duplication in the ancestral vertebrates. Based
      on synteny and phylogenetic evidence, the present naming of the GAT group members
      does not accurately reflect the evolutionary relationships. 

PMID- 24312661
TI  - Confidence intervals for fMRI activation maps.
AB  - Neuroimaging activation maps typically color voxels to indicate whether the blood
      oxygen level-dependent (BOLD) signals measured among two or more experimental
      conditions differ significantly at that location. This data presentation,
      however, omits information critical for interpretation of experimental results.
      First, no information is represented about trends at voxels that do not pass the
      statistical test. Second, no information is given about the range of probable
      effect sizes at voxels that do pass the statistical test. This leads to a
      fundamental error in interpreting activation maps by naive viewers, where it is
      assumed that colored, "active" voxels are reliably different from uncolored
      "inactive" voxels. In other domains, confidence intervals have been added to data
      graphics to reduce such errors. Here, we first document the prevalence of the
      fundamental error of interpretation, and then present a method for solving it by
      depicting confidence intervals in fMRI activation maps. Presenting images where
      the bounds of confidence intervals at each voxel are coded as color allows
      readers to visually test for differences between "active" and "inactive" voxels,
      and permits for more proper interpretation of neuroimaging data. Our specific
      graphical methods are intended as initial proposals to spur broader discussion of
      how to present confidence intervals for fMRI data. 

PMID- 24312662
TI  - Immunogenicity of individual vaccine components in a bivalent nicotine vaccine
      differ according to vaccine formulation and administration conditions.
AB  - Structurally distinct nicotine immunogens can elicit independent antibody
      responses against nicotine when administered concurrently. Co-administering
      different nicotine immunogens together as a multivalent vaccine could be a useful
      way to generate higher antibody levels than with monovalent vaccines alone. The
      immunogenicity and additivity of monovalent and bivalent nicotine vaccines was
      studied across a range of immunogen doses, adjuvants, and routes to assess the
      generality of this approach. Rats were vaccinated with total immunogen doses of
      12.5-100 MUg of 3'-aminomethyl nicotine conjugated to recombinant Pseudomonas
      exoprotein A (3'-AmNic-rEPA), 6-carboxymethylureido nicotine conjugated to
      keyhole limpet hemocyanin (6-CMUNic-KLH), or both. Vaccines were administered
      s.c. in alum or i.p. in Freund's adjuvant at matched total immunogen doses. When
      administered s.c. in alum, the contributions of the individual immunogens to
      total nicotine-specific antibody (NicAb) titers and concentrations were preserved
      across a range of doses. Antibody affinity for nicotine varied greatly among
      individuals but was similar for monovalent and bivalent vaccines. However when
      administered i.p. in Freund's adjuvant the contributions of the individual
      immunogens to total NicAb titers and concentrations were compromised at some
      doses. These results support the possibility of co-administering structurally
      distinct nicotine immunogens to achieve a more robust immune response than can be
      obtained with monovalent immunogens alone. Choice of adjuvant was important for
      the preservation of immunogen component activity.

PMID- 24312663
TI  - Optimization of the piggyBac transposon using mRNA and insulators: toward a more
      reliable gene delivery system.
AB  - Integrating and expressing stably a transgene into the cellular genome remain
      major challenges for gene-based therapies and for bioproduction purposes. While
      transposon vectors mediate efficient transgene integration, expression may be
      limited by epigenetic silencing, and persistent transposase expression may
      mediate multiple transposition cycles. Here, we evaluated the delivery of the
      piggyBac transposase messenger RNA combined with genetically insulated
      transposons to isolate the transgene from neighboring regulatory elements and
      stabilize expression. A comparison of piggyBac transposase expression from
      messenger RNA and DNA vectors was carried out in terms of expression levels,
      transposition efficiency, transgene expression and genotoxic effects, in order to
      calibrate and secure the transposition-based delivery system. Messenger RNA
      reduced the persistence of the transposase to a narrow window, thus decreasing
      side effects such as superfluous genomic DNA cleavage. Both the CTF/NF1 and the
      D4Z4 insulators were found to mediate more efficient expression from a few
      transposition events. We conclude that the use of engineered piggyBac transposase
      mRNA and insulated transposons offer promising ways of improving the quality of
      the integration process and sustaining the expression of transposon vectors. 

PMID- 24312664
TI  - Response of the ubiquitous pelagic diatom Thalassiosira weissflogii to darkness
      and anoxia.
AB  - Thalassiosira weissflogii, an abundant, nitrate-storing, bloom-forming diatom in
      the world's oceans, can use its intracellular nitrate pool for dissimilatory
      nitrate reduction to ammonium (DNRA) after sudden shifts to darkness and anoxia,
      most likely as a survival mechanism. T. weissflogii cells that stored 4 mM (15)N
      nitrate consumed 1.15 (+/-0.25) fmol NO3 (-) cell(-1) h(-1) and simultaneously
      produced 1.57 (+/-0.21) fmol (15)NH4 (+) cell(-1) h(-1) during the first 2 hours
      of dark/anoxic conditions. Ammonium produced from intracellular nitrate was
      excreted by the cells, indicating a dissimilatory rather than assimilatory
      pathway. Nitrite and the greenhouse gas nitrous oxide were produced at rates 2-3
      orders of magnitude lower than the ammonium production rate. While DNRA activity
      was restricted to the first few hours of darkness and anoxia, the subsequent
      degradation of photopigments took weeks to months, supporting the earlier finding
      that diatoms resume photosynthesis even after extended exposure to darkness and
      anoxia. Considering the high global abundance of T. weissflogii, its production
      of ammonium and nitrous oxide might be of ecological importance for oceanic
      oxygen minimum zones and the atmosphere, respectively. 

PMID- 24312665
TI  - Increased adiposity in annexin A1-deficient mice.
AB  - Production of Annexin A1 (ANXA1), a protein that mediates the anti-inflammatory
      action of glucocorticoids, is altered in obesity, but its role in modulation of
      adiposity has not yet been investigated. The objective of this study was to
      investigate modulation of ANXA1 in adipose tissue in murine models of obesity and
      to study the involvement of ANXA1 in diet-induced obesity in mice. Significant
      induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c
      mice with high fat diet (HFD)-induced obesity versus mice on chow diet.
      Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by
      use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female
      Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by
      significantly elevated body weight, fat mass, leptin levels, and adipocyte size.
      Whereas Balb/c WT mice upregulated expression of enzymes involved in the
      lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice.
      A significant increase in fasting glucose and insulin levels as well as
      development of insulin resistance was observed in ANXA1 KO mice on HFD compared
      to WT mice. Elevated plasma corticosterone levels and blunted downregulation of
      11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in
      ANXA1 KO mice compared to diet-matched WT mice. However, no differences between
      WT and KO mice on either chow or HFD were observed in expression of markers of
      adipose tissue inflammation. These data indicate that ANXA1 is an important
      modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background
      being more susceptible to weight gain and diet-induced insulin resistance
      compared to WT mice, without significant changes in inflammation. 

PMID- 24312666
TI  - Phenotypic convergence in genetically distinct lineages of a Rhinolophus species
      complex (Mammalia, Chiroptera).
AB  - Phenotypes of distantly related species may converge through adaptation to
      similar habitats and/or because they share biological constraints that limit the
      phenotypic variants produced. A common theme in bats is the sympatric occurrence
      of cryptic species that are convergent in morphology but divergent in
      echolocation frequency, suggesting that echolocation may facilitate niche
      partitioning, reducing competition. If so, allopatric populations freed from
      competition, could converge in both morphology and echolocation provided they
      occupy similar niches or share biological constraints. We investigated the
      evolutionary history of a widely distributed African horseshoe bat, Rhinolophus
      darlingi, in the context of phenotypic convergence. We used phylogenetic
      inference to identify and date lineage divergence together with phenotypic
      comparisons and ecological niche modelling to identify morphological and
      geographical correlates of those lineages. Our results indicate that R. darlingi
      is paraphyletic, the eastern and western parts of its distribution forming two
      distinct non-sister lineages that diverged ~9.7 Mya. We retain R. darlingi for
      the eastern lineage and argue that the western lineage, currently the sub-species
      R. d. damarensis, should be elevated to full species status. R. damarensis
      comprises two lineages that diverged ~5 Mya. Our findings concur with patterns of
      divergence of other co-distributed taxa which are associated with increased
      regional aridification between 7-5 Mya suggesting possible vicariant evolution.
      The morphology and echolocation calls of R. darlingi and R. damarensis are
      convergent despite occupying different biomes. This suggests that adaptation to
      similar habitats is not responsible for the convergence. Furthermore, R. darlingi
      forms part of a clade comprising species that are bigger and echolocate at lower
      frequencies than R. darlingi, suggesting that biological constraints are unlikely
      to have influenced the convergence. Instead, the striking similarity in
      morphology and sensory biology are probably the result of neutral evolutionary
      processes, resulting in the independent evolution of similar phenotypes. 

PMID- 24312667
TI  - Markers of thrombogenesis and fibrinolysis and their relation to inflammation and
      endothelial activation in patients with idiopathic pulmonary arterial
      hypertension.
AB  - BACKGROUND: Chronic anticoagulation is a standard of care in idiopathic pulmonary
      arterial hypertension (IPAH). However, hemostatic abnormalities in this disease
      remain poorly understood. Therefore, we aimed to study markers of thrombogenesis
      and fibrinolysis in patients with IPAH. METHODS: We studied 27 consecutive
      patients (67% female) with IPAH aged 50.0 years (IQR: 41.0-65.0) and 16 controls
      without pulmonary hypertension. Prothrombin fragment 1+2 (F1+2) and thrombin
      antithrombin (TAT) complexes were measured to assess thrombogenesis; tissue-type
      plasminogen activator (tPA) antigen and plasmin-anti-plasmin complex to
      characterize activation of fibrinolysis; plasminogen activator inhibitor 1 (PAI
      1) to measure inhibition of fibrinolysis; and endothelin-1 (ET-1) and interleukin
      6 (IL-6) to assess endothelial activation and systemic inflammation,
      respectively. In addition, in treatment-naive IPAH patients these markers were
      assessed after 3 months of PAH-specific therapies. RESULTS: TPA (10.1[6.8-15.8]
      vs 5.2[3.3-7.3] ng/ml, p<0.001), plasmin-anti-plasmin (91.5[60.3-94.2] vs
      55.8[51.1-64.9] ng/ml, p<0.001), IL-6 (4.9[2.5-7.9] vs 2.1[1.3-3.8] pg/ml,
      p=0.001) and ET-1 (3.7 [3.3-4.5] vs 3.4[3.1-3.5], p= 0.03) were higher in
      patients with IPAH than in controls. In IPAH patients plasmin-anti-plasmin and
      tPA correlated positively with IL-6 (r=0.39, p=0.04 and r=0.63, p<0.001,
      respectively) and ET-1 (r=0.55, p=0.003 and r=0.59, p=0.001, respectively). No
      correlation was found between tPA or plasmin-anti-plasmin and markers of
      thrombogenesis. Plasmin-anti-plasmin decreased after 3 months of PAH specific
      therapy while the other markers remained unchanged. CONCLUSIONS: In the present
      study we showed that markers of fibrynolysis were elevated in patients with IPAH
      however we did not find a clear evidence for increased thrombogenesis in this
      group of patients. Fibrinolysis, inflammation, and endothelial activation were
      closely interrelated in IPAH.

PMID- 24312668
TI  - Rates of fetal polydrug exposures in methadone-maintained pregnancies from a high
      risk population.
AB  - Methadone maintenance treatment (MMT) is the standard of care during pregnancy
      for opioid-dependency, showing efficacy in improving prenatal care and reducing
      risk of relapse. By design, however, MMT is only intended to prevent withdrawal
      thus facilitating cognitive behavioural interventions. In order to maximize the
      benefits of MMT, it is essential that methadone is both properly prescribed and
      that additional addiction treatment is concurrently administered. This study aims
      to determine the effectiveness of MMT engagement in high-risk pregnant women in
      reducing polydrug use by objective laboratory examination of neonatal meconium.
      PATIENTS AND METHODS: Over a 29-month period, the Motherisk Laboratory at the
      Hospital for Sick Children in Toronto analyzed meconium samples as per request by
      social services and hospitals for drugs of abuse. RESULTS: Of the 904 meconium
      samples received, 273 were tested for methadone with 164 positive and 109
      negative for methadone. Almost half of the methadone positive samples (46.34%)
      were also positive for at least one other opioid compound, which did not differ
      statistically from the methadone-negative control samples (46.79%; Chi square
      test, p=0.94). No differences were found between the methadone positive and
      negative groups in rates of concurrent amphetamines, cocaine, cannabis, and
      alcohol use indicating a similar risk of polydrug use between pregnant women
      taking or not taking methadone in this population. DISCUSSION: The high rates of
      additional opioid and other drug use in the MMT group, suggest that MMT is
      failing this population of patients. It is possible that methadone doses during
      pregnancy are not appropriately adjusted for changes in pharmacokinetic
      parameters (e.g. blood volume, renal function) during the second and third
      trimesters. This may result in sub-therapeutic dosing creating withdrawal
      symptoms leading to additional substance use. Alternatively, these results may be
      demonstrating a substantial lack in delivery of addiction support services in
      this vulnerable population.

PMID- 24312669
TI  - Surfactant protein A binds flagellin enhancing phagocytosis and IL-1beta
      production.
AB  - Surfactant protein A (SP-A), a pulmonary collectin, plays a role in lung innate
      immune host defense. In this study the role of SP-A in regulating the
      inflammatory response to the flagella of Pseudomonas aeruginosa (PA) was
      examined. Intra-tracheal infection of SP-A deficient (SP-A-/-) C57BL/6 mice with
      wild type flagellated PA (PAK) resulted in an increase in inflammatory cell
      recruitment and increase in pro-inflammatory cytokines IL-6 and TNF-alpha, which
      was not observed with a mutant pseudomonas lacking flagella (fliC). SP-A directly
      bound flagellin, via the N-linked carbohydrate moieties and collagen-like domain,
      in a concentration dependent manner and enhanced macrophage phagocytosis of
      flagellin and wild type PAK. IL-1beta was reduced in the lungs of SP-A-/- mice
      following PAK infection. MH-s cells, a macrophage cell line, generated greater IL
      1beta when stimulated with flagellin and SP-A. Historically flagella stimulate IL
      1beta production through the toll-like receptor 5 (TLR-5) pathway and through a
      caspase-1 activating inflammasome pathway. IL-1beta expression became non
      detectable in SP-A and flagellin stimulated MH-s cells in which caspase-1 was
      silenced, suggesting SP-A induction of IL-1beta appears to be occurring through
      the inflammasome pathway. SP-A plays an important role in the pathogenesis of PA
      infection in the lung by binding flagellin, enhancing its phagocytosis and
      modifying the macrophage inflammatory response. 

PMID- 24312671
TI  - Serum prolactin and macroprolactin levels among outpatients with major depressive
      disorder following the administration of selective serotonin-reuptake inhibitors:
      a cross-sectional pilot study.
AB  - Clinical trials evaluating the rate of short-term selective serotonin-reuptake
      inhibitor (SSRI)-induced hyperprolactinemia have produced conflicting results.
      Thus, the aim of this study was to clarify whether SSRI therapy can induce
      hyperprolactinemia and macroprolactinemia. Fifty-five patients with major
      depressive disorder (MDD) were enrolled in this study. Serum prolactin and
      macroprolactin levels were measured at a single time point (i.e., in a cross
      sectional design). All patients had received SSRI monotherapy (escitalopram,
      paroxetine, or sertraline) for a mean of 14.75 months. Their mean prolactin level
      was 15.26 ng/ml. The prevalence of patients with hyperprolactinemia was 10.9% for
      6/55, while that of patients with macroprolactinemia was 3.6% for 2/55. The mean
      prolactin levels were 51.36 and 10.84 ng/ml among those with hyperprolactinemia
      and a normal prolactin level, respectively. The prolactin level and prevalence of
      hyperprolactinemia did not differ significantly within each SSRI group.
      Correlation analysis revealed that there was no correlation between the dosage of
      each SSRI and prolactin level. These findings suggest that SSRI therapy can
      induce hyperprolactinemia in patients with MDD. Clinicians should measure and
      monitor serum prolactin levels, even when both SSRIs and antipsychotics are
      administered. 

PMID- 24312670
TI  - Mak5 and Ebp2 act together on early pre-60S particles and their reduced
      functionality bypasses the requirement for the essential pre-60S factor Nsa1.
AB  - Ribosomes are the molecular machines that translate mRNAs into proteins. The
      synthesis of ribosomes is therefore a fundamental cellular process and consists
      in the ordered assembly of 79 ribosomal proteins (r-proteins) and four ribosomal
      RNAs (rRNAs) into a small 40S and a large 60S ribosomal subunit that form the
      translating 80S ribosomes. Most of our knowledge concerning this dynamic multi
      step process comes from studies with the yeast Saccharomyces cerevisiae, which
      have shown that assembly and maturation of pre-ribosomal particles, as they
      travel from the nucleolus to the cytoplasm, relies on a multitude (>200) of
      biogenesis factors. Amongst these are many energy-consuming enzymes, including 19
      ATP-dependent RNA helicases and three AAA-ATPases. We have previously shown that
      the AAA-ATPase Rix7 promotes the release of the essential biogenesis factor Nsa1
      from late nucleolar pre-60S particles. Here we show that mutant alleles of genes
      encoding the DEAD-box RNA helicase Mak5, the C/D-box snoRNP component Nop1 and
      the rRNA-binding protein Nop4 bypass the requirement for Nsa1. Interestingly,
      dominant-negative alleles of RIX7 retain their phenotype in the absence of Nsa1,
      suggesting that Rix7 may have additional nuclear substrates besides Nsa1. Mak5 is
      associated with the Nsa1 pre-60S particle and synthetic lethal screens with mak5
      alleles identified the r-protein Rpl14 and the 60S biogenesis factors Ebp2, Nop16
      and Rpf1, which are genetically linked amongst each other. We propose that these
      'Mak5 cluster' factors orchestrate the structural arrangement of a eukaryote
      specific 60S subunit surface composed of Rpl6, Rpl14 and Rpl16 and rRNA expansion
      segments ES7L and ES39L. Finally, over-expression of Rix7 negatively affects
      growth of mak5 and ebp2 mutant cells both in the absence and presence of Nsa1,
      suggesting that Rix7, at least when excessively abundant, may act on structurally
      defective pre-60S subunits and may subject these to degradation. 

PMID- 24312672
TI  - A quality control mechanism linking meiotic success to release of ascospores.
AB  - Eukaryotic organisms employ a variety of mechanisms during meiosis to assess and
      ensure the quality of their gametes. Defects or delays in successful meiotic
      recombination activate conserved mechanisms to delay the meiotic divisions, but
      many multicellular eukaryotes also induce cell death programs to eliminate
      gametes deemed to have failed during meiosis. It is generally thought that yeasts
      lack such mechanisms. Here, we show that in the fission yeast Schizosaccharomyces
      pombe, defects in meiotic recombination lead to the activation of a checkpoint
      that is linked to ascus wall endolysis--the process by which spores are released
      in response to nutritional cues for subsequent germination. Defects in meiotic
      recombination are sensed as unrepaired DNA damage through the canonical ATM and
      ATR DNA damage response kinases, and this information is communicated to the
      machinery that stimulates ascus wall breakdown. Viability of spores that undergo
      endolysis spontaneously is significantly higher than that seen upon chemical
      endolysis, demonstrating that this checkpoint contributes to a selective
      mechanism for the germination of high quality progeny. These results provide the
      first evidence for the existence of a checkpoint linking germination to meiosis
      and suggest that analysis solely based on artificial, enzymatic endolysis
      bypasses an important quality control mechanism in this organism and potentially
      other ascomycota, which are models widely used to study meiosis.

PMID- 24312673
TI  - Chromosomes in the porcine first polar body possess competence of second meiotic
      division within enucleated MII stage oocytes.
AB  - To determine whether chromosomes in the porcine first polar body (PB1) can
      complete the second meiotic division and subsequently undergo normal pre
      implantation embryonic development, we examined the developmental competence of
      PB1 chromosomes injected into enucleated MII stage oocytes by nuclear transfer
      method (chromosome replacement group, CR group). After parthenogenetic activation
      (PA) or in vitro fertilization (IVF), the cleavage rate of reconstructed oocytes
      in the IVF group (CR-IVF group, 36.4 +/- 3.2%) and PA group (CR-PA group, 50.8 +/
      4.2%) were significantly lower than that of control groups in which normal MII
      oocytes were subjected to IVF (MII-IVF group, 75.8 +/- 1.5%) and PA (MII-PA
      group, 86.9 +/- 3.7%). Unfertilized rates was significantly higher in the CR-IVF
      group (48.6 +/- 3.3%) than in the MII-IVF group (13.1 +/- 3.4%). The blastocyst
      formation rate was 8.3 +/- 1.9% in the CR-PA group, whereas no blastocyst
      formation was observed in the CR-IVF group. To produce tetraploid parthenogenetic
      embryos, intact MII stage oocytes injected with PB1 chromosomes were electrically
      stimulated, treated with 7.5 MUg/mL cytochalasin B for 3 h (MII oocyte + PB1 + CB
      group), and then cultured without cytochalasin B. The average cleavage rate of
      reconstructed oocytes was 72.5% (48 of 66), and the blastocyst formation rate was
      18.7% (9 of 48). Chromosome analysis showed similar proportions of haploid and
      diploid cells in the control (normal MII oocytes) and CR groups after PA;
      overall, 23.6% of blastocysts were tetraploid in the MII oocyte + PB1 + CB group.
      These results demonstrate that chromosomes in PB1 can participate in normal pre
      implantation embryonic development when injected into enucleated MII stage
      oocytes, and that tetraploid PA blastocysts are produced (although at a low
      proportion) when PB1 chromosomes are injected into intact MII stage oocytes.

PMID- 24312674
TI  - The mitochondrial genome of Arctica islandica; Phylogeny and variation.
AB  - Arctica islandica is known as the longest-lived non-colonial metazoan species on
      earth and is therefore increasingly being investigated as a new model in aging
      research. As the mitochondrial genome is associated with the process of aging in
      many species and bivalves are known to possess a peculiar mechanism of
      mitochondrial genome inheritance including doubly uniparental inheritance (DUI),
      we aimed to assess the genomic variability of the A. islandica mitochondrial DNA
      (mtDNA). We sequenced the complete mitochondrial genomes of A. islandica
      specimens from three different sites in the Western Palaearctic (Iceland, North
      Sea, Baltic Sea). We found the A. islandica mtDNA to fall within the normal size
      range (18 kb) and exhibit similar coding capacity as other animal mtDNAs. The
      concatenated protein sequences of all currently known Veneroidea mtDNAs were used
      to robustly place A. islandica in a phylogenetic framework. Analysis of the
      observed single nucleotide polymorphism (SNP) patterns on further specimen
      revealed two prevailing haplotypes. Populations in the Baltic and the North Sea
      are very homogenous, whereas the Icelandic population, from which exceptionally
      old individuals have been collected, is the most diverse one. Homogeneity in
      Baltic and North Sea populations point to either stronger environmental
      constraints or more recent colonization of the habitat. Our analysis lays the
      foundation for further studies on A. islandica population structures, age
      research with this organism, and for phylogenetic studies. Accessions for the
      mitochondrial genome sequences: KC197241 Iceland; KF363951 Baltic Sea; KF363952
      North Sea; KF465708 to KF465758 individual amplified regions from different
      speciemen. 

PMID- 24312675
TI  - Vitamin A deficiency impairs adaptive B and T cell responses to a prototype
      monovalent attenuated human rotavirus vaccine and virulent human rotavirus
      challenge in a gnotobiotic piglet model.
AB  - Rotaviruses (RV) are a major cause of gastroenteritis in children. Widespread
      vitamin A deficiency is associated with reduced efficacy of vaccines and higher
      incidence of diarrheal infections in children in developing countries. We
      established a vitamin A deficient (VAD) gnotobiotic piglet model that mimics
      subclinical vitamin A deficiency in children to study its effects on an oral
      human rotavirus (HRV) vaccine and virulent HRV challenge. Piglets derived from
      VAD and vitamin A sufficient (VAS) sows were orally vaccinated with attenuated
      HRV or mock, with/without supplemental vitamin A and challenged with virulent
      HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A,
      higher severity and duration of diarrhea and HRV fecal shedding post-challenge as
      compared to VAS control pigs. Reduced protection coincided with significantly
      higher innate (IFNalpha) cytokine and CD8 T cell frequencies in the blood and
      intestinal tissues, higher pro-inflammatory (IL12) and 2-3 fold lower anti
      inflammatory (IL10) cytokines, in VAD compared to VAS control pigs. Vaccinated
      VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs,
      which coincided with lower serum IgA HRV antibody titers and significantly lower
      intestinal IgA antibody secreting cells post-challenge in the former groups
      suggesting lower anamnestic responses. A trend for higher serum HRV IgG
      antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The
      vaccinated VAD (non-vitamin A supplemented) pigs had significantly higher serum
      IL12 (PID2) and IFNgamma (PID6) compared to vaccinated VAS groups suggesting
      higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses
      were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully
      restore the dysregulated immune responses to AttHRV vaccine or moderate virulent
      HRV diarrhea. Our findings suggest that that VAD in children in developing
      countries may partially contribute to more severe rotavirus infection and lower
      HRV vaccine efficacy. 

PMID- 24312676
TI  - miR-homoHSV of Singapore grouper iridovirus (SGIV) inhibits expression of the
      SGIV pro-apoptotic factor LITAF and attenuates cell death.
AB  - Growing evidence demonstrates that various large DNA viruses could encode
      microRNAs (miRNAs) that regulate host and viral genes to achieve immune evasion.
      In this study, we report that miR-homoHSV, an miRNA encoded by Singapore grouper
      iridovirus (SGIV), can attenuate SGIV-induced cell death. Mechanistically, SGIV
      miR-homoHSV targets SGIV ORF136R, a viral gene that encodes the pro-apoptotic
      lipopolysaccharide-induced TNF-alpha (LITAF)-like factor. miR-homoHSV suppressed
      exogenous and endogenous SGIV LITAF expression, and thus inhibited SGIV LITAF
      induced apoptosis. Meanwhile, miR-homoHSV expression was able to attenuate cell
      death induced by viral infection, presumably facilitating viral replication
      through the down-regulation of the pro-apoptotic gene SGIV LITAF. Together, our
      data suggest miR-homoHSV may serve as a feedback regulator of cell death during
      viral infection. The findings of this study provide a better understanding of
      SGIV replication and pathogenesis. 

PMID- 24312677
TI  - The contribution of head movement to the externalization and internalization of
      sounds.
AB  - BACKGROUND: When stimuli are presented over headphones, they are typically
      perceived as internalized; i.e., they appear to emanate from inside the head.
      Sounds presented in the free-field tend to be externalized, i.e., perceived to be
      emanating from a source in the world. This phenomenon is frequently attributed to
      reverberation and to the spectral characteristics of the sounds: those sounds
      whose spectrum and reverberation matches that of free-field signals arriving at
      the ear canal tend to be more frequently externalized. Another factor, however,
      is that the virtual location of signals presented over headphones moves in
      perfect concert with any movements of the head, whereas the location of free
      field signals moves in opposition to head movements. The effects of head movement
      have not been systematically disentangled from reverberation and/or spectral
      cues, so we measured the degree to which movements contribute to externalization.
      METHODOLOGY/PRINCIPAL FINDINGS: We performed two experiments: 1) Using motion
      tracking and free-field loudspeaker presentation, we presented signals that moved
      in their spatial location to match listeners' head movements. 2) Using motion
      tracking and binaural room impulse responses, we presented filtered signals over
      headphones that appeared to remain static relative to the world. The results from
      experiment 1 showed that free-field signals from the front that move with the
      head are less likely to be externalized (23%) than those that remain fixed (63%).
      Experiment 2 showed that virtual signals whose position was fixed relative to the
      world are more likely to be externalized (65%) than those fixed relative to the
      head (20%), regardless of the fidelity of the individual impulse responses.
      CONCLUSIONS/SIGNIFICANCE: Head movements play a significant role in the
      externalization of sound sources. These findings imply tight integration between
      binaural cues and self motion cues and underscore the importance of self motion
      for spatial auditory perception.

PMID- 24312678
TI  - Methylation of the SLC6a2 gene promoter in major depression and panic disorder.
AB  - Reduced function of the noradrenaline transporter (NET) has been demonstrated in
      patients with major depressive disorder (MDD) and panic disorder. Attempts to
      explain NET dysfunction in MDD and panic disorder by genetic variation in the NET
      gene SLC6a2 have been inconclusive. Transcriptional silencing of the SLC6a2 gene
      may be an alternative mechanism which can lead to NET dysfunction independent of
      DNA sequence. The objective of this study was to characterise the DNA methylation
      state of the SLC6a2 gene promoter in patients with MDD and panic disorder. SLC6a2
      promoter methylation was also analysed before and after antidepressant treatment.
      This study was performed with DNA from blood, using bisulphite sequencing and
      EpiTYPER methylation analyses. Patients with MDD or panic disorder were not found
      to differ significantly from healthy controls in the pattern of methylation of
      the SLC6a2 gene promotor. While significant correlations between methylation
      levels at some CpG sites and physiological measures were identified, overall the
      variation in DNA methylation between patients was small, and the significance of
      this variation remains equivocal. No significant changes in SLC6a2 promoter
      methylation were observed in response to antidepressant treatment. Further in
      depth analysis of alternative mechanisms of transcriptional regulation of the
      SLC6a2 gene in human health and disease would be of value. 

PMID- 24312680
TI  - Indoor air pollution, nighttime heart rate variability and coffee consumption
      among convenient store workers.
AB  - BACKGROUND: The association between ambient air pollution and heart rate
      variability (HRV) has been well-documented. Little is known about the association
      of HRV at night with indoor air pollution and coffee consumption. The aim of this
      study was to investigate the association of HRV indices with indoor air
      pollution, working time and coffee consumption. METHODS: We recruited 60 young
      healthy convenient store workers to monitor indoor PM2.5 (particulate matter with
      an aerodynamic diameter <= 2.5 um) exposures, coffee consumption (yes vs. no) and
      HRV indices during daytime (0700-1500 hours) and nighttime (2300-0700 hours). We
      used linear mixed effects models to assess the associations of HRV indices with
      indoor PM2.5 exposures and coffee consumption. RESULTS: We observed the inverse
      association between indoor PM2.5 exposures and HRV indices, with a decrease in
      all HRV indices with increased indoor PM2.5 exposures. However, the decrease was
      most pronounced during nighttime, where a 1 interquartile range (IQR) increase in
      indoor PM2.5 at 4-hr time-weighted moving average was associated with a change of
      -4.78% 5-min standard deviation (SD) of normal-to-normal intervals for 5-min
      segment (SDNN) and -3.23% 5-min square root of the mean squared differences of
      successive intervals for 5-min segment (r-MSSD). Effects of indoor PM2.5 were
      lowest for participants with coffee consumption during daytime. CONCLUSIONS:
      Indoor PM2.5 exposures were associated with decreased 5-min SDNN and 5-min r
      MSSD, especially during nighttime. The effect of indoor PM2.5 on HRV indices may
      be modified by coffee consumption in young healthy convenient store workers.

PMID- 24312679
TI  - Role of mTOR downstream effector signaling molecules in Francisella tularensis
      internalization by murine macrophages.
AB  - Francisella tularensis is an infectious, gram-negative, intracellular
      microorganism, and the cause of tularemia. Invasion of host cells by
      intracellular pathogens like Francisella is initiated by their interaction with
      different host cell membrane receptors and the rapid phosphorylation of different
      downstream signaling molecules. PI3K and Syk have been shown to be involved in F.
      tularensis host cell entry, and both of these signaling molecules are associated
      with the master regulator serine/threonine kinase mTOR; yet the involvement of
      mTOR in F. tularensis invasion of host cells has not been assessed. Here, we
      report that infection of macrophages with F. tularensis triggers the
      phosphorylation of mTOR downstream effector molecules, and that signaling via
      TLR2 is necessary for these events. Inhibition of mTOR or of PI3K, ERK, or p38,
      but not Akt signaling, downregulates the levels of phosphorylation of mTOR
      downstream targets, and significantly reduces the number of F. tularensis cells
      invading macrophages. Moreover, while phosphorylation of mTOR downstream
      effectors occurs via the PI3K pathway, it also involves PLCgamma1 and Ca(2+)
      signaling. Furthermore, abrogation of PLC or Ca(2+) signaling revealed their
      important role in the ability of F. tularensis to invade host cells. Together,
      these findings suggest that F. tularensis invasion of primary macrophages utilize
      a myriad of host signaling pathways to ensure effective cell entry. 

PMID- 24312681
TI  - Lysophosphatidylcholine triggers TLR2- and TLR4-mediated signaling pathways but
      counteracts LPS-induced NO synthesis in peritoneal macrophages by inhibiting NF
      kappaB translocation and MAPK/ERK phosphorylation.
AB  - BACKGROUND: Lysophosphatidylcholine (LPC) is the main phospholipid component of
      oxidized low-density lipoprotein (oxLDL) and is usually noted as a marker of
      several human diseases, such as atherosclerosis, cancer and diabetes. Some
      studies suggest that oxLDL modulates Toll-like receptor (TLR) signaling. However,
      effector molecules that are present in oxLDL particles and can trigger TLR
      signaling are not yet clear. LPC was previously described as an attenuator of
      sepsis and as an immune suppressor. In the present study, we have evaluated the
      role of LPC as a dual modulator of the TLR-mediated signaling pathway.
      METHODOLOGY/PRINCIPAL FINDINGS: HEK 293A cells were transfected with TLR
      expression constructs and stimulated with LPC molecules with different fatty acid
      chain lengths and saturation levels. All LPC molecules activated both TLR4 and
      TLR2-1 signaling, as evaluated by NF-?B activation and IL-8 production. These
      data were confirmed by Western blot analysis of NF-?B translocation in isolated
      nuclei of peritoneal murine macrophages. However, LPC counteracted the TLR4
      signaling induced by LPS. In this case, NF-?B translocation, nitric oxide (NO)
      synthesis and the expression of inducible nitric oxide synthase (iNOS) were
      blocked. Moreover, LPC activated the MAP Kinases p38 and JNK, but not ERK, in
      murine macrophages. Interestingly, LPC blocked LPS-induced ERK activation in
      peritoneal macrophages but not in TLR-transfected cells.
      CONCLUSIONS/SIGNIFICANCE: The above results indicate that LPC is a dual-activity
      ligand molecule. It is able to trigger a classical proinflammatory phenotype by
      activating TLR4- and TLR2-1-mediated signaling. However, in the presence of
      classical TLR ligands, LPC counteracts some of the TLR-mediated intracellular
      responses, ultimately inducing an anti-inflammatory phenotype; LPC may thus play
      a role in the regulation of cell immune responses and disease progression.

PMID- 24312683
TI  - Advances in the Treatment of Pancreatic Neuroendocrine Tumors (pNETs).
AB  - Recent clinical trials have led to significant advancements in treatment options
      for metastatic neuroendocrine tumors of the pancreas. Sunitinib and everolimus
      have been approved by the Food and Drug Administration for treatment of
      progressive pancreatic NETs based on phase III trial data demonstrating
      improvements in progression-free survival. Cytotoxic drugs such as temozolomide
      and capecitabine have been associated with high radiographic response rates;
      however data derives primarily from subset analysis of prospective trials and
      from retrospective series. During the next few years, randomized clinical trials
      are expected to provide more clarity on the role of somatostatin analogs and
      cytotoxic drugs. New studies are also evaluating biomarkers that will potentially
      allow for improved selection of drugs for specific tumor subtypes. 

PMID- 24312682
TI  - Strategies for detection of Plasmodium species gametocytes.
AB  - Carriage and density of gametocytes, the transmission stages of malaria
      parasites, are determined for predicting the infectiousness of humans to
      mosquitoes. This measure is used for evaluating interventions that aim at
      reducing malaria transmission. Gametocytes need to be detected by amplification
      of stage-specific transcripts, which requires RNA-preserving blood sampling. For
      simultaneous, highly sensitive quantification of both, blood stages and
      gametocytes, we have compared and optimized different strategies for field and
      laboratory procedures in a cross sectional survey in 315 5-9 yr old children from
      Papua New Guinea. qRT-PCR was performed for gametocyte markers pfs25 and pvs25,
      Plasmodium species prevalence was determined by targeting both, 18S rRNA genes
      and transcripts. RNA-based parasite detection resulted in a P. falciparum
      positivity of 24.1%; of these 40.8% carried gametocytes. P. vivax positivity was
      38.4%, with 38.0% of these carrying gametocytes. Sensitivity of DNA-based
      parasite detection was substantially lower with 14.1% for P. falciparum and 19.6%
      for P. vivax. Using the lower DNA-based prevalence of asexual stages as a
      denominator increased the percentage of gametocyte-positive infections to 59.1%
      for P. falciparum and 52.4% for P. vivax. For studies requiring highly sensitive
      and simultaneous quantification of sexual and asexual parasite stages, 18S rRNA
      transcript-based detection saves efforts and costs. RNA-based positivity is
      considerably higher than other methods. On the other hand, DNA-based parasite
      quantification is robust and permits comparison with other globally generated
      molecular prevalence data. Molecular monitoring of low density asexual and sexual
      parasitaemia will support the evaluation of effects of up-scaled antimalarial
      intervention programs and can also inform about small scale spatial variability
      in transmission intensity. 

PMID- 24312684
TI  - A Phase II Trial of Cetuximab, Gemcitabine, 5-Fluorouracil, and Radiation Therapy
      in Locally Advanced Nonmetastatic Pancreatic Adenocarcinoma.
AB  - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer deaths in the
      United States. A minority of patients present with localized disease and surgical
      resection still offers patients the only hope for long-term survival. Locally
      advanced pancreatic cancer is defined as surgically unresectable, but has no
      evidence of distant metastases. The purpose of this study is to evaluate the
      efficacy and safety of cetuximab in combination with gemcitabine and 5-FU along
      with radiation therapy in locally advanced non-resectable, pancreatic
      adenocarcinoma, using progression free survival as the primary end point.
      METHODS: This was a prospective, single arm, open label pilot phase II study to
      evaluate the anti-tumor activity of gemcitabine (200 mg/m(2) per week) and
      cetuximab (250 mg/m(2) per week after an initial 400 mg/m(2) loading dose) with
      continuous infusion 5-FU (800 mg/m(2) over 96 hours) and daily concurrent
      external beam radiation therapy (50.4 Gy total dose) for six weeks (cycle 1) in
      patients with non-metastatic, locally advanced pancreatic adenocarcinoma.
      Following neoadjuvant treatment, subjects were re-evaluated for response and
      surgical candidacy with restaging scans. After resection, or also if not
      resected; subjects received further therapy with four 28-day cycles (cycles 2-5)
      of weekly gemcitabine (1000 mg/m(2)) and cetuximab (250 mg/m(2)) on days 1, 8,
      and 15. RESULTS: Between 2006 and 2011, twenty-six patients were screened and
      eleven of them were enrolled in the study. Most common reasons for screen
      failures were having resectable disease, metastatic disease or co-morbidity. Ten
      patients were able to tolerate and complete cycle 1 of chemoradiotherapy. One
      patient stopped the study prematurely due to grade III diarrhea. All except this
      one patient received planned radiation therapy. The response evaluation after
      cycle 1 showed one Partial Response, eight Stable Disease and two Progressive
      Disease. Four patients subsequently underwent surgical resection of the tumor.
      All patients had R0 resections. There was one preoperative mortality due to
      multiple organ failure. Median progression free survival (PFS) for four resected
      patients was 9.0 months while for unresected patients median PFS was 7.1 months.
      Median overall survival (OS) for four resected patients was 47.4 months and for
      unresected patients median OS was 17.0 months. Most common adverse events were
      hematologic (27%). Only two patients developed grade 3 neutropenia. Most common
      treatment related non-hematologic adverse events were diarrhea (10 of 11), nausea
      (8 of 11) and skin rash (10 of 11 patients). Only 9.5% of all reported non
      hematologic adverse events were grade 3 or higher. CONCLUSIONS: The combination
      of cetuximab, weekly gemcitabine and continuous infusion of 5-FU with
      radiotherapy was quite well tolerated with intriguing clinical benefit and
      survival results in carefully selected patients with locally advanced pancreatic
      adenocarcinoma. A trial with larger sample size will be necessary to confirm
      these results.

PMID- 24312686
TI  - Predictors of acute gastrointestinal toxicity during pelvic chemoradiotherapy in
      patients with rectal cancer.
AB  - BACKGROUND: This study was conducted to identify the factors associated with
      acute gastrointestinal (GI) toxicity during pelvic chemoradiotherapy (PCRT) in
      patients with rectal cancer. METHODS: We analyzed 177 patients with rectal cancer
      treated from 2007 through 2010. Clinical information, including weekly diarrhea
      and proctitis toxicity grade during PCRT, was recorded. GI structures including
      bowel and anal canal were contoured. The associations between toxicity and
      clinical and dosimetric predictors were tested. RESULTS: The median age was 60;
      76 patients were women; 98 were treated with intensity-modulated radiotherapy
      (IMRT) and 79 with 3D conformal RT (3DCRT). A higher rate of grade 2+ diarrhea
      was observed in the women, starting at week 4 (24% women vs. 11% men, P = .01;
      week 5: 33% vs. 12%, P = .002), as well as in all the patients treated with 3DCRT
      (22% vs. 12% IMRT, P = .03; week 5: 32% vs. 11%, P = .001). On multivariate
      analysis, the normal tissue complication probability (NTCP) model including bowel
      V45 (bowel volume receiving >=45 Gy) showed that being female, and use of 3DCRT,
      was most predictive of grade 2+ diarrhea (area under the curve [AUC] = 0.76; R S
      = 0.35; P < .001). A higher rate of grade 2+ proctitis was seen in patients <60
      years of age starting at week 3 (21% vs. 9%, P = .02; week 4: 35% vs. 16%, P =
      .003). The NTCP model including anal canal V15 and younger age was most
      predictive of grade 2+ proctitis (AUC = 0.67; R S = 0.25; P < .001). CONCLUSIONS:
      Women and all patients who were treated with 3DCRT had higher rates of grade 2+
      diarrhea, and the younger patients had a higher rate of grade 2+ proctitis during
      PCRT. The use of more stringent dosimetric constraints in higher risk patients is
      a strategy for minimizing toxicity.

PMID- 24312687
TI  - Acute gastrointestinal toxicity and tumor response with preoperative intensity
      modulated radiation therapy for rectal cancer.
AB  - BACKGROUND: Preoperative chemoradiotherapy (preopCRT) for locally advanced rectal
      cancer is associated with grade 3 or higher acute gastrointestinal (GI) toxicity.
      This study was conducted to determine whether intensity-modulated radiation
      therapy (IMRT) significantly reduces acute GI toxicity, compared to 3-dimensional
      conformal RT (3D-CRT) in preopCRT for rectal cancer. METHODS: A retrospective
      analysis was conducted of 48 patients treated between January 2002 and August
      2010 with preopCRT for rectal cancer. 3D-CRT or IMRT was administered at a
      planned dose of 45-50.4 Gy to patients positioned prone on a bowel-displacement
      device. Data regarding patient and tumor characteristics, treatment, acute
      toxicity, and tumor response were collected. Comparisons of acute toxicity and
      treatment response between 3D-CRT and IMRT were performed with the Chi-square or
      Fisher's exact test. RESULTS: There were no significant differences in radiation
      dose, median age, race, gender, stage, type of concurrent chemotherapy,
      pathologic complete response (pCR), or type of surgery (lower anterior or
      abdominal perineal resection) between 3D-CRT and IMRT. There was a significant
      reduction in grade 2 or higher GI toxicity (3D-CRT, 60.7%; IMRT, 30%; P = .036)
      and grade 2 or higher diarrhea (3D-CRT, 42.8%; IMRT, 10%; P = .014). Two patients
      who underwent 3D-CRT required a treatment break (grade 3 diarrhea and grade 3
      dehydration). Radiation duration was significantly less (IMRT, 35 days; 3D-CRT,
      39 days; P <= .0001). pCR rates were 16.7% for 3D-CRT and 21.4% for IMRT
      (nonsignificant [NS]); pCR+microscopic residual rates were 57.1% for IMRT and
      27.8% for 3D-CRT (P = .093). CONCLUSION: Maximal bowel displacement with IMRT
      yields favorable acute GI toxicity and pathologic downstaging profiles, as
      compared to 3D-CRT in preoperative CRT for rectal cancer and warrants further
      prospective investigation.

PMID- 24312688
TI  - A giant rectal villous adenoma with a malicious intent.

PMID- 24312689
TI  - Melanoma metastasis to the gastric mucosa preceded by guillain-barre as a
      paraneoplastic syndrome.

PMID- 24312692
TI  - Upcoming articles.

PMID- 24312690
TI  - Metastatic colon cancer presenting as pituitary mass.

PMID- 24312693
TI  - Gastrointestinal cancer research official journal of the international society of
      gastrointestinal oncology contents of volume 6, issues 1-6 january-december 2013.

PMID- 24312694
TI  - Diazinon-induced ulcerative keratitis in C57bl/6 mice.
AB  - As a well-known organophosphate insecticide, diazinon (DZN) has been used for
      several decades in agriculture. The major signs of ophthalmic toxicity of DZN
      have been reported to be cholinergic overstimulation (lacrimation, myosis). Here,
      we report, for the first time, ulcerative keratitis in C57bl/6 mice secondary to
      sub-acute exposure to DZN. Four groups of female C57bl/6 mice were administered
      intraperitoneally either DZN (1, 5, 25 mg/kg/day) or vehicle for 14 consecutive
      days. Then, histopathological examinations on mice eyes were performed using
      light microscope and scored for corneal keratitis. Furthermore, blood
      cholinesterase activity, and hematologic examinations were performed. Data
      indicated a significant ulcerative keratitis with prompt vision loss in mice
      exposed to 25 and 5 mg/kg/day (P < 0.05) doses. These results suggest that
      diazinon might induce ulcerative keratitis secondary to its immunosuppresive
      effects at high doses in C57bl/6 mice. 

PMID- 24312695
TI  - Xenotransplantation of embryonic pig pancreas for treatment of diabetes mellitus
      in non-human primates.
AB  - Transplantation therapy for diabetes in humans is limited by the low availability
      of human donor whole pancreas or islets. Outcomes are complicated by
      immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome
      supply problems. Implantation of tissue obtained early during embryogenesis is a
      way to reduce transplant immunogenicity. Pig insulin is biologically active in
      humans. In that regard the pig is an appropriate xenogeneic organ donor. Insulin
      producing cells originating from embryonic pig pancreas obtained very early
      following pancreatic primordium formation [embryonic day 28 (E28)] engraft long
      term in rhesus macaques. Endocrine cells originating from embryonic pig pancreas
      transplanted in host mesentery migrate to mesenteric lymph nodes, engraft,
      differentiate and improve glucose tolerance in rhesus macaques without the need
      for immune suppression. Transplantation of embryonic pig pancreas is a novel
      approach towards beta cell replacement therapy that could be applicable to
      humans.

PMID- 24312696
TI  - Transient acidosis during early reperfusion attenuates myocardium ischemia
      reperfusion injury via PI3k-Akt-eNOS signaling pathway.
AB  - In this paper, we concluded that transient acidosis reperfusion conferred
      cardioprotection against myocardial ischemia reperfusion injury in isolated rat
      hearts through activating PI3K-Akt-eNOS pathway. 

PMID- 24312697
TI  - Protective effects of low-frequency magnetic fields on cardiomyocytes from
      ischemia reperfusion injury via ROS and NO/ONOO-.
AB  - BACKGROUND: Cardiac ischemia reperfusion (I/R) injury is associated with
      overproduction of reactive oxygen species (ROS). Low frequency pulse magnetic
      fields (LFMFs) have been reported to decrease ROS generation in endothelial
      cells. Whether LFMFs could assert protective effects on myocardial from I/R
      injury via ROS regulation remains unclear. METHODS: To simulate in vivo cardiac
      I/R injury, neonatal rat cardiomyocytes were subjected to hypoxia reoxygenation
      (H/R) with or without exposure to LFMFs. Cell viability, apoptosis index, ROS
      generation (including O2(-) and ONOO(-)), and NO production were measured in
      control, H/R, and H/R + LFMF groups, respectively. RESULTS: H/R injury resulted
      in cardiomyocytes apoptosis and decreased cell viability, whereas exposure to
      LFMFs before or after H/R injury significantly inhibited apoptosis and improved
      cell viability (P < 0.05). LFMFs treatment could suppress ROS (including O2(-)
      and ONOO(-)) generation induced by H/R injury, combined with decreased NADPH
      oxidase activity. In addition, LFMFs elevated NO production and enhanced NO/ONOO(
      ) balance in cardiomyocytes, and this protective effect was via the
      phosphorylation of endothelial nitric oxide synthase (eNOS). CONCLUSION: LFMFs
      could protect myocardium against I/R injury via regulating ROS generation and
      NO/ONOO(-) balance. LFMFs treatment might serve as a promising strategy for
      cardiac I/R injury.

PMID- 24312698
TI  - Malnutrition in Sickle Cell Anemia: Implications for Infection, Growth, and
      Maturation.
AB  - Sickle cell anemia (SCA) is a genetic disease that affects mostly individuals of
      African and/or Hispanic descent, with the majority of cases in sub-Saharan
      Africa. Individuals with this disease show slowed growth, delayed sexual
      maturity, and poor immunologic function. These complications could partly be
      explained by the state of undernutrition associated with the disease. Proposed
      mechanism of undernutrition include protein hypermetabolism, decreased dietary
      intake possibly from interleukin-6-related appetite suppression, increased
      cardiac energy demand/expenditure, and increased red cell turnover. All the above
      mechanisms manifest as increased resting energy expenditure. Nutritional
      intervention utilizing single or multiple nutrient supplementation has led to
      improved clinical outcome, growth, and sexual maturation. Studies are currently
      underway to determine the best possible approach to applying nutritional
      intervention in the management of SCA. Management of SCA will, of necessity,
      involve a nutritional component, given the sociodemographic distribution of those
      most affected by the disease, the ease of a nutritional approach, and the wider
      reach that such an approach will embody.

PMID- 24312699
TI  - Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as
      Anti-Cancer Agents.
AB  - The rhodacyanine, MKT-077, has anti-proliferative activity against cancer cell
      lines through its ability to inhibit members of the heat shock protein 70 (Hsp70)
      family of molecular chaperones. However, MKT-077 is rapidly metabolized, which
      limits its use as either a chemical probe or potential therapeutic. We report the
      synthesis and characterization of MKT-077 analogs designed for greater stability.
      The most potent molecules, such as 30 (JG-98), were at least 3-fold more active
      than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50
      values of 0.4 +/- 0.03 MUM and 0.7 +/- 0.2 MUM, respectively). The analogs
      modestly destabilized the chaperone "clients", Akt1 and Raf1, and induced
      apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved
      at least 7-fold (t1/2 = 37 min) compared to MKT-077 (t1/2 < 5 min). Finally, NMR
      titration experiments suggested that these analogs bind an allosteric site that
      is known to accommodate MKT-077. These studies advance MKT-077 analogs as
      chemical probes for studying Hsp70's roles in cancer.

PMID- 24312700
TI  - Computer-aided Drug Design: Using Numbers to your Advantage.
AB  - Computer-aided drug design could benefit from a greater understanding of how
      errors arise and propagate in biomolecular modeling. With such knowledge, model
      predictions could be associated with quantitative estimates of their uncertainty.
      In addition, novel algorithms could be designed to proactively reduce prediction
      errors. We investigated how errors propagate in statistical mechanical ensembles
      and found that free energy evaluations based on single molecular configurations
      yield maximum uncertainties in free energy. Furthermore, increasing the size of
      the ensemble by sampling and averaging over additional independent configurations
      reduces uncertainties in free energy dramatically. This finding suggests a
      general strategy that could be utilized as a post-hoc correction for improved
      precision in virtual screening and free energy estimation.

PMID- 24312701
TI  - Effects of Macromolecular Crowding on the Conformational Ensembles of Disordered
      Proteins.
AB  - Due to their conformational malleability, intrinsically disordered proteins
      (IDPs) are particularly susceptible to influences of crowded cellular
      environments. Here we report a computational study of the effects of
      macromolecular crowding on the conformational ensemble of a coarse-grained IDP
      model, by using two approaches. In one, the IDP is simulated along with the
      crowders; in the other, crowder-free simulations are postprocessed to predict the
      conformational ensembles under crowding. We found significant decreases in the
      radius of gyration of the IDP under crowding, and suggest repulsive interactions
      with crowders as a common cause for chain compaction in a number of experimental
      studies. The postprocessing approach accurately reproduced the conformational
      ensembles of the IDP in the direct simulations here, and holds enormous potential
      for realistic modeling of IDPs under crowding, by permitting thorough
      conformation sampling for the proteins even when they and the crowders are both
      represented at the all-atom level.

PMID- 24312703
TI  - Prediction of risk of malignancy of gastrointestinal stromal tumors by endoscopic
      ultrasonography.
AB  - BACKGROUND/AIMS: The accurate preoperative prediction of the risk of malignancy
      of gastrointestinal stromal tumors (GISTs) is difficult. The aim of this study
      was to determine whether tumor size and endoscopic ultrasonography (EUS) features
      can preoperatively predict the risk of malignancy of medium-sized gastric GISTs.
      METHODS: Surgically resected, 2 to 5 cm gastric GIST patients were enrolled and
      retrospectively reviewed. EUS features, such as heterogeneity, hyperechoic foci,
      calcification, cystic change, hypoechoic foci, lobulation, and ulceration, were
      evaluated. Tumors were grouped in 1 cm intervals. The correlations of tumor size
      or EUS features with the risk of malignancy were evaluated. RESULTS: A total of
      75 patients were enrolled. The mean tumor size was 3.43+/-0.92 cm. Regarding the
      risk of malignancy, 51 tumors (68%) had a very low risk, and 24 tumors (32%) had
      a moderate risk. When the tumors were divided into three groups in 1 cm
      intervals, the proportions of tumors with a moderate risk were not different
      between the groups. The preoperative EUS features also did not differ between the
      very low risk and the moderate risk groups. CONCLUSIONS: Tumor size and EUS
      features cannot be used to preoperatively predict the risk of malignancy of
      medium-sized gastric GISTs. A preoperative diagnostic modality for predicting
      risk of malignancy is necessary to prevent the overtreatment of GISTs with a low
      risk of malignancy.

PMID- 24312704
TI  - Seroprevalence of Helicobacter pylori Infection in Korean Health Personnel.
AB  - BACKGROUND/AIMS: The aims of this study were to evaluate whether doctors and
      nurses in a single hospital were at an increased risk of acquiring Helicobacter
      pylori infection in 2011 and to identify risk factors for H. pylori
      seroprevalence. METHODS: Nurses (n=362), doctors (n=110), health personnel
      without patient contact (medical control, n=179), and nonhospital controls
      (n=359) responded to a questionnaire during a health check-up, which included
      questions on socioeconomic status, education level, working years, and occupation
      in 2011. The prevalence of H. pylori was measured by serology. RESULTS: The
      seroprevalence rate was 29.8% (nurses), 34.5% (doctors), 30.7% (medical control),
      and 52.9% (nonhospital control). Among younger subjects (<40 years of age), the
      nonhospital control had a higher seropositivity rate (48.1%) than nurses (29.2%),
      doctors (29.8%), and the medical control (24.8%), which was not observable in
      subjects >=40 years of age. The risk factors for H. pylori seroprevalence were
      not different for health and nonhealth personnel. A multivariate analysis
      indicated that seropositivity significantly increased with age, the province of
      residence, and a gastroscopic finding of a peptic ulcer. CONCLUSIONS: The medical
      occupation was not associated with H. pylori infection. The seroprevalence of H.
      pylori in one hospital in 2011 was found to be 38.7%, most likely due to the
      improvement in socioeconomic status and hospital hygiene policy in Korea.

PMID- 24312702
TI  - Increasing the alpha 2, 6 sialylation of glycoproteins may contribute to
      metastatic spread and therapeutic resistance in colorectal cancer.
AB  - Abnormal glycosylation due to dysregulated glycosyltransferases and glycosidases
      is a key phenomenon of many malignancies, including colorectal cancer (CRC). In
      particular, increased ST6 Gal I (beta-galactoside alpha 2, 6 sialyltransferase)
      and subsequently elevated levels of cell-surface alpha 2, 6-linked sialic acids
      have been associated with metastasis and therapeutic failure in CRC. As many CRC
      patients experience metastasis to the liver or lung and fail to respond to
      curative therapies, intensive research efforts have sought to identify the
      molecular changes underlying CRC metastasis. ST6 Gal I has been shown to
      facilitate CRC metastasis, and we believe that additional investigations into the
      involvement of ST6 Gal I in CRC could facilitate the development of new
      diagnostic and therapeutic targets. This review summarizes how ST6 Gal I has been
      implicated in the altered expression of sialylated glycoproteins, which have been
      linked to CRC metastasis, radioresistance, and chemoresistance. 

PMID- 24312705
TI  - Substitutions in penicillin-binding protein 1 in amoxicillin-resistant
      Helicobacter pylori strains isolated from Korean patients.
AB  - BACKGROUND/AIMS: A worldwide increase in amoxicillin resistance in Helicobacter
      pylori is having an adverse effect on eradication therapy. In this study, we
      investigated the mechanism of the amoxicillin resistance of H. pylori in terms of
      amino acid substitutions in penicillin-binding protein 1 (PBP1). METHODS: In
      total, 150 H. pylori strains were isolated from 144 patients with chronic
      gastritis, peptic ulcers, or stomach cancer. The minimum inhibitory
      concentrations (MICs) of the strains were determined with a serial 2-fold agar
      dilution method. The resistance breakpoint for amoxicillin was defined as >0.5
      ug/mL. RESULTS: Nine of 150 H. pylori strains showed amoxicillin resistance (6%).
      The MIC values of the resistant strains ranged from 1 to 4 ug/mL. A PBP1 sequence
      analysis of the resistant strains revealed multiple amino acid substitutions:
      Val16->Ile, Val45->Ile, Ser414->Arg, Asn562->Tyr, Thr593->Ala, Gly595->Ser, and
      Ala599->Thr. The natural transformation of these mutated genes into amoxicillin
      sensitive strains was performed in two separate pbp1 gene segments. A moderate
      increase in the amoxicillin MIC was observed in the segment that contained the
      penicillin-binding motif of the C-terminal portion, the transpeptidase domain.
      CONCLUSIONS: pbp1 mutation affects the amoxicillin resistance of H. pylori
      through the transfer of the penicillin-binding motif.

PMID- 24312706
TI  - Seasonal variation in months of birth and symptom flares in Korean patients with
      inflammatory bowel disease.
AB  - BACKGROUND/AIMS: Seasonal variation may influence the development and
      exacerbation of inflammatory bowel disease (IBD). However, most epidemiologic
      studies on this topic have been conducted in Western countries. The purpose of
      this study was to determine whether birth dates and symptom flares follow a
      seasonal pattern in Korean patients with IBD. METHODS: Patients with a diagnosis
      of IBD established between January 2003 and December 2010 were investigated at
      six university hospitals in Korea. The expected births and flares, with a uniform
      distribution during the year and considering differences in the number of days in
      the months of 1 year, were calculated. RESULTS: A total of 411 patients with
      ulcerative colitis (UC) and 316 patients with Crohn disease (CD) were included in
      the study. Birth during the winter period, and especially in January and
      February, was associated with an increased risk of IBD, especially in UC
      patients. The symptom flares of CD patients occurred most frequently in the
      spring, with a nadir in the autumn. However, no disease flare seasonality was
      noted for UC patients. CONCLUSIONS: Our data suggest that seasonally varying
      environmental factors during pregnancy and the postpartum period are associated
      with a susceptibility to IBD later in life and that exacerbations of CD are
      influenced by seasonal factors.

PMID- 24312707
TI  - Concomitant functional gastrointestinal symptoms influence psychological status
      in Korean migraine patients.
AB  - BACKGROUND/AIMS: Migraine is frequently accompanied by symptoms consistent with
      functional gastrointestinal disorders (FGIDs). This study evaluated the
      prevalence of functional gastrointestinal symptoms and assessed the symptoms'
      relationship with the concomitant functional symptoms of anxiety, depression, and
      headache-related disability. METHODS: This prospective study included 109
      patients with migraine who were recruited from a headache clinic at a teaching
      hospital. The participants completed a self-administered survey that collected
      information on headache characteristics, functional gastrointestinal symptoms
      (using Rome III criteria to classify FGID), anxiety, depression, and headache
      related disability. RESULTS: In total, 71% of patients met the Rome III criteria
      for at least one FGID. In patients with FGID, irritable bowel syndrome was the
      most common symptom (40.4%), followed by nausea and vomiting syndrome (24.8%) and
      functional dyspepsia (23.9%). Depression and anxiety scores were significantly
      higher in patients meeting the criteria for any FGID. The number of the symptoms
      consistent with FGID in individual patients correlated positively with depression
      and anxiety. CONCLUSIONS: FGID symptoms defined by the Rome III criteria are
      highly prevalent in migraine. These symptoms correlate with psychological
      comorbidities, such as depression and anxiety.

PMID- 24312708
TI  - Ischemia-modified albumin: could it be a new oxidative stress biomarker for
      colorectal carcinoma?
AB  - BACKGROUND/AIMS: An impaired oxidative/antioxidative status plays an important
      role in the pathogenesis of many diseases, including cancer. The aim of this
      study was to evaluate the levels of the novel marker ischemia-modified albumin
      (IMA) and albumin-adjusted IMA (Adj-IMA) in patients with colorectal cancer (CRC)
      and look for the associations of these with the total antioxidant status (TAS),
      total oxidant status (TOS), and oxidative stress index (OSI). METHODS: Forty
      patients with CRC (19 females and 21 males; mean age, 56.5+/-2.1 years) and 39
      age- and sex-matched healthy people (22 females and 17 males; mean age, 56.0+/
      1.7 years) were included in this study. Serum levels of IMA, TAS, and TOS were
      analyzed, and the OSI was calculated. RESULTS: Serum IMA, TOS, and OSI levels
      were significantly higher in patients with CRC than in controls (p<0.0001),
      whereas TAS levels were significantly lower in CRC patients (p=0.03). There was
      no significant difference in serum Adj-IMA levels between groups (p=0.32).
      CONCLUSIONS: In this study, the oxidative/antioxidant status was impaired in
      favor of oxidative stress in CRC patients. This observation was not confirmed by
      IMA measurement. Further studies are needed to establish the relationship between
      IMA and oxidative stress parameters in CRC and other cancers.

PMID- 24312709
TI  - A clear liquid diet is not mandatory for polyethylene glycol-based bowel
      preparation for afternoon colonoscopy in healthy outpatients.
AB  - BACKGROUND/AIMS: A dietary regimen consisting of a clear liquid diet (CLD) for at
      least 24 hours is recommended for colonoscopy preparation. However, this
      requirement results in problems in patient compliance with bowel preparation. The
      aim of this study was to evaluate the efficacy of a CLD compared with a regular
      diet (RD) for colonoscopy preparation using a polyethylene glycol (PEG) solution.
      METHODS: This was a multicenter, randomized, investigator-blind prospective
      study. A total of 801 healthy outpatients undergoing afternoon colonoscopy were
      randomized to either a CLD or RD in addition to a 4 L PEG regimen. RESULTS: The
      quality of bowel cleansing was not different between the CLD and RD groups in
      terms of the proportion with excellent or good preparation. In addition, no
      significant differences were observed between the two groups for polyp and
      adenoma detection rates and overall adverse events. Good compliance with bowel
      preparation was higher in the RD group than in the CLD group. CONCLUSIONS: A CLD
      for a full day prior to colonoscopy should not be mandatory for PEG-based bowel
      preparation. Dietary education concerning the avoidance of high-fiber foods for 3
      days before colonoscopy is sufficient, at least for healthy outpatients.

PMID- 24312710
TI  - An inverse relationship between the expression of the gastric tumor suppressor
      RUNX3 and infection with Helicobacter pylori in gastric epithelial dysplasia.
AB  - BACKGROUND/AIMS: This study was performed to determine the association between
      RUNX3 expression and Helicobacter pylori infection in premalignant gastric
      lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who
      had undergone endoscopic mucosal resection or submucosal dissection. All tissue
      samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H.
      pylori infection in dysplastic lesions and the normal surrounding tissue was
      examined by silver staining, and cagA status was assessed by polymerase chain
      reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%),
      and an association with H. pylori infection was found in 54 cases (50.5%). The
      infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3
      negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of
      category 4 lesions (according to the revised Vienna classification) were high
      (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3
      negative category 4 lesions, the rate of cagA-positive H. pylori infection rate
      was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H.
      pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis.
      This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

PMID- 24312711
TI  - Practical effect of sorafenib monotherapy on advanced hepatocellular carcinoma
      and portal vein tumor thrombosis.
AB  - BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced
      hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a
      clinical setting. METHODS: In total, 143 consecutive patients with unresectable
      HCC were treated with sorafenib. Among these patients, 30 patients with advanced
      HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All
      patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group
      1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had
      modified Union for International Cancer Control stage IVA tumors, whereas 19 had
      stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib
      monotherapy, three patients (10.0%) had a partial response with PVTT
      revascularization, and nine (30.0%) had stable disease, with a disease control
      rate of 33.3%. The median overall survival was 3.1 months (95% confidence
      interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0
      months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most
      troublesome side effects. CONCLUSIONS: A limited proportion of patients with
      advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy,
      although the treatment results in this type of patient is extremely poor. Further
      studies to predict good responders to personalized therapy are warranted.

PMID- 24312712
TI  - The risk factors for bleeding of fundal varices in patients with liver cirrhosis.
AB  - BACKGROUND/AIMS: The relationship between portal hemodynamics and fundal varices
      has not been well documented. The purpose of this study was to understand the
      pathophysiology of fundal varices and to investigate bleeding risk factors
      related to the presence of spontaneous portosystemic shunts, and to examine the
      hepatic venous pressure gradient (HVPG) between fundal varices and other varices.
      METHODS: In total, 85 patients with cirrhosis who underwent HVPG and gastroscopic
      examination between July 2009 and March 2011 were included in this study. The
      interrelationship between HVPG and the types of varices or the presence of
      spontaneous portosystemic shunts was studied. RESULTS: There was no significant
      difference in the HVPG between fundal varices (n=12) and esophageal varices and
      gastroesophageal varices type 1 (GOV1) groups (n=73) (17.1+/-7.7 mm Hg vs 19.7+/
      5.3 mm Hg). Additionally, there was no significant difference in the HVPG between
      varices with spontaneous portosystemic shunts (n=28) and varices without these
      shunts (n=57) (18.3+/-5.8 mm Hg vs 17.0+/-8.1 mm Hg). Spontaneous portosystemic
      shunts increased in fundal varices compared with esophageal varices and GOV1
      (8/12 patients [66.7%] vs 20/73 patients [27.4%]; p=0.016). CONCLUSIONS: Fundal
      varices had a high prevalence of spontaneous portosystemic shunts compared with
      other varices. However, the portal pressure in fundal varices was not different
      from the pressure in esophageal varices and GOV1.

PMID- 24312713
TI  - Continuous long-term entecavir therapy in naive chronic hepatitis B patients
      showing partial virologic response.
AB  - BACKGROUND/AIMS: We investigated the efficacy of continuous long-term entecavir
      0.5 mg treatment in naive chronic hepatitis B patients showing a partial
      virologic response (PVR). METHODS: A total of 227 patients were included. PVR was
      defined as a more than 1 log10 IU/mL decline in detectable serum hepatitis B
      virus (HBV) DNA by polymerase chain reaction (PCR; >=20 IU/mL) at week 48. A
      complete virologic response (CVR) was defined as undetectable serum HBV DNA by
      PCR (<20 IU/mL) at week 48. RESULTS: At week 48, the rate of the PVR was 64/227
      (28.2%). Among patients with PVR, the cumulative rates of virologic response
      (serum HBV DNA <20 IU/mL) at weeks 96 and 144 were 45.2% and 73.8%, respectively.
      The cumulative rates of genotypic resistance were not significantly different
      between patients with a PVR and patients with a CVR (p=0.057). However, the
      cumulative rates of virologic breakthrough were higher in patients with PVR than
      in patients with CVR (4% vs 0% and 11.2% vs 0% at weeks 96 and 144, respectively;
      p<0.001). CONCLUSIONS: Long-term continuous entecavir 0.5 mg treatment in
      patients with a PVR resulted in an additional virologic response without a
      significant increase in genotypic resistance. However, the rate of virologic
      breakthrough was higher in the partial responders.

PMID- 24312714
TI  - Changes in demographic features of gallstone disease: 30 years of surgically
      treated patients.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate changes in the clinical
      and demographical characteristics of gallstone disease in Korea, based on 30
      years of surgically treated patients at a single institute. METHODS: In total,
      7,949 gallstone patients who underwent surgery between 1981 and 2010 were
      analyzed. Patients were divided into six time periods: period I (1981 to 1985,
      n=831), period II (1986 to 1990, n=888), period III (1991 to 1995, n=1,040),
      period IV (1996 to 2000, n=1,261), period V (2001 to 2005, n=1,651) and period VI
      (2006 to 2010, n=2,278). RESULTS: The total number and mean age of the patients
      gradually increased, and the male/female ratio decreased. The proportion of
      gallbladder (GB)-stone cases increased, whereas the proportions of common bile
      duct (CBD)- and intrahepatic duct (IHD)-stone cases decreased. Differences in
      patient geographical origins also decreased. Based on the relationship between
      changes in the prevalence of gallstone disease and socioeconomic status, the
      prevalence of CBD stones showed a strong correlation with Engel's coefficient
      (p<0.001). CONCLUSIONS: Our study indicates that although the total number of
      cases and the mean age of gallstone patients have continuously increased, there
      are trends of increasing GB-stone cases and decreasing CBD- and IHD-stone cases.

PMID- 24312715
TI  - A novel, fully covered laser-cut nitinol stent with antimigration properties for
      nonresectable distal malignant biliary obstruction: a multicenter feasibility
      study.
AB  - BACKGROUND/AIMS: Stent migration occurs frequently, but the prevention of
      complications resulting from covered self-expandable metal stents (C-SEMSs)
      remains unresolved. We prospectively assessed a newly developed C-SEMS, a
      modified covered Zeo stent (m-CZS), in terms of its antimigration effect.
      METHODS: Between February 2010 and January 2011, an m-CZS was inserted into 42
      patients (31 initial drainage cases and 11 reintervention cases) at a tertiary
      referral center and three affiliated hospitals. The laser-cut stent was flared
      for 1.5 cm at both ends, with a 1 cm raised bank located 1 cm in from each flared
      end. The main outcome of this study was the rate of stent migration, and
      secondary outcomes were the rate of recurrent biliary obstruction (RBO), the time
      to RBO, the frequencies of complications, and overall survival. RESULTS: Of the
      31 patients with initial drainage, stent migration occurred in four (12.9%, 95%
      confidence interval, 5.1% to 29.0%), with a mean time of 131 days. RBO occurred
      in 18 (58%), with a median time to RBO of 107 days. Following previous C-SEMS
      migration, seven of 10 patients (70%) did not experience m-CZS migration until
      death. CONCLUSIONS: m-CZSs with antimigration properties effectively, although
      not completely, prevented stent migration after stent insertion.

PMID- 24312716
TI  - Intra-abdominal pressure in the early phase of severe acute pancreatitis: canary
      in a coal mine? Results from a rigorous validation protocol.
AB  - BACKGROUND/AIMS: Intra-abdominal hypertension (IAH) is being increasingly
      reported in patients with severe acute pancreatitis (SAP) with worsened outcomes.
      The present study was undertaken to evaluate intra-abdominal pressure (IAP) as a
      marker of severity in the entire spectrum of acute pancreatitis and to ascertain
      the relationship between IAP and development of complications in patients with
      SAP. METHODS: IAP was measured via the transvesical route by measurements
      performed at admission, once after controlling pain and then every 4 hours. Data
      were collected on the length of the hospital stay, the development of systemic
      inflammatory response syndrome (SIRS), multiorgan failure, the extent of
      necrosis, the presence of infection, pleural effusion, and mortality. RESULTS: In
      total, 40 patients were enrolled and followed up for 30 days. The development of
      IAH was exclusively associated with SAP with an APACHE II score >=8 and/or
      persistent SIRS, identifying all patients who were going to develop abdominal
      compartment syndrome (ACS). The presence of ACS was associated with a
      significantly increased extent of pancreatic necrosis, multiple organ failure,
      and mortality. The mean admission IAP value did not differ significantly from the
      value obtained after pain control or the maximum IAP measured in the first 5
      days. CONCLUSIONS: IAH is reliable marker of severe disease, and patients who
      manifest organ failure, persistent SIRS, or an Acute Physiology and Chronic
      health Evaluation II score >=8 should be offered IAP surveillance. Severe
      pancreatitis is not a homogenous entity.

PMID- 24312717
TI  - Expression of heat shock protein 70 modulates the chemoresponsiveness of
      pancreatic cancer.
AB  - BACKGROUND/AIMS: Heat shock protein (HSP) 70 is constitutively overexpressed in
      pancreatic cancer cells (PCCs) and appears to confer protection against
      chemotherapeutics. We investigated whether modulating HSP 70 increases
      chemoresponsiveness to gemcitabine in PCCs. METHODS: Varying concentrations of
      quercetin and gemcitabine, either alone or in combination, were added to PCCs
      (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70
      expression was assessed by Western blot analysis. Apoptosis was determined by
      measuring caspase-3 activity. Western blot for the LC3-II protein detected the
      presence of autophagy. RESULTS: HSP 70 levels were not affected by the incubation
      of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the
      levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa
      2 cells significantly decreased with gemcitabine treatment but not with
      quercetin. A combination of gemcitabine and quercetin decreased the viability of
      both cell lines in a dose-dependent manner, which was more pronounced than
      gemcitabine treatment alone. Treatment with either gemcitabine or quercetin
      augmented caspase-3 activity in both cell lines, and a combination of these
      compounds further potentiated caspase-3 activity. LC3-II protein expression was
      negligible with gemcitabine treatment but marked with quercetin. The addition of
      gemcitabine to quercetin did not potentiate LC3-II protein expression.
      CONCLUSIONS: Modulation of HSP 70 expression with quercetin enhanced the
      chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both
      apoptosis and autophagy.

PMID- 24312718
TI  - A novel germline mutation in exon 10 of the SMAD4 gene in a familial juvenile
      polyposis.
AB  - Familial juvenile polyposis (FJP) is a rare autosomal dominant hereditary
      disorder that is characterized by the development of multiple distinct juvenile
      polyps in the gastrointestinal tract and an increased risk of cancer. Recently,
      germline mutations, including mutations in the SMAD4, BMPR1A, PTEN and, possibly,
      ENG genes, have been found in patients with juvenile polyps. We herein report a
      family with juvenile polyposis syndrome (JPS) with a novel germline mutation in
      the SMAD4 gene. A 21-year-old man presented with rectal bleeding and was found to
      have multiple polyps in his stomach, small bowel, and colon. His mother had a
      history of gastrectomy for multiple gastric polyps with anemia and a history of
      colectomy for colon cancer. A review of the histology of the polyps revealed
      juvenile polyps in both patients. Subsequently, mutation screening in DNA samples
      from the patients revealed a germline mutation in the SMAD4 gene. The pair had a
      novel mutation in exon 10 (stop codon at tyrosine 413). To our knowledge, this
      mutation has not been previously described. Careful family history collection and
      genetic screening in JPS patients are needed to identify FJP, and regular
      surveillance is recommended. 

PMID- 24312719
TI  - Solitary rectal ulcer syndrome in children: a report of six cases.
AB  - Solitary rectal ulcer syndrome (SRUS) is a rare, benign disorder in children that
      usually presents with rectal bleeding, constipation, mucous discharge, prolonged
      straining, tenesmus, lower abdominal pain, and localized pain in the perineal
      area. The underlying etiology is not well understood, but it is secondary to
      ischemic changes and trauma in the rectum associated with paradoxical contraction
      of the pelvic floor and the external anal sphincter muscles; rectal prolapse has
      also been implicated in the pathogenesis. This syndrome is diagnosed based on
      clinical symptoms and endoscopic and histological findings, but SRUS often goes
      unrecognized or is easily confused with other diseases such as inflammatory bowel
      disease, amoebiasis, malignancy, and other causes of rectal bleeding such as a
      juvenile polyps. SRUS should be suspected in patients experiencing rectal
      discharge of blood and mucus in addition to previous disorders of evacuation. We
      herein report six pediatric cases with SRUS. 

PMID- 24312720
TI  - Performance characteristics of a new flexible nitinol 19-gauge endoscopic
      ultrasound-guided fine needle aspiration needle.

PMID- 24312721
TI  - An evaluation of ICD-11 PTSD and complex PTSD criteria in a sample of adult
      survivors of childhood institutional abuse.
AB  - BACKGROUND: The WHO recently launched the proposal for the 11th version of the
      International Classification of Diseases (ICD-11) that also includes two
      diagnoses related to traumatic stress. In contrast to the Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), ICD-11 will
      probably, in addition to posttraumatic stress disorder (PTSD), also define a new
      diagnosis termed "complex posttraumatic stress disorder" (CPTSD). OBJECTIVE: We
      aimed to apply the proposed ICD-11 criteria for PTSD and CPTSD and to compare
      their prevalence to the ICD-10 (International Classification of Diseases [10th
      revision]) PTSD prevalence. In addition, we compiled a list of symptoms for CPTSD
      based on subthreshold PTSD so as to include a wider group of individuals.
      METHODS: To evaluate the appropriateness of the WHO ICD-11 proposal compared to
      the criteria of ICD-10, we applied the newly introduced criteria for PTSD and
      CPTSD deriving from the Posttraumatic Stress Disorder Checklist - Civilian
      Version (PCL-C) and the Brief Symptom Inventory (BSI) scales, to a sample of
      adult survivors (N=229) of childhood institutional abuse. We evaluated the
      construct validity of CPTSD using confirmatory factor analysis (CFA). RESULTS:
      More individuals fulfilled the criteria for PTSD according to ICD-10 (52.8%) than
      the ICD-11 proposal (17% for PTSD only; 38.4% if combined with complex PTSD). The
      new version of PTSD neutralized the gender effects. The prevalence of CPTSD was
      21.4%, and women had a significantly higher rate of CPTSD than men (40.4 and
      15.8%, respectively). Those survivors who were diagnosed with CPTSD experienced
      institutional abuse for a longer time. CFA showed a strong model fit. CONCLUSION:
      CPTSD is a highly relevant classification for individuals with complex trauma
      history, but surprisingly, effects of gender were apparent. Further research
      should thus address gender effects.

PMID- 24312722
TI  - Carbocyclic 5'-nor "reverse" fleximers. Design, synthesis, and preliminary
      biological activity.
AB  - A series of 5'-nor carbocyclic "reverse" flexible nucleosides or "fleximers" have
      been designed wherein the nucleobase scaffold resembles a "split" purine as well
      as a substituted pyrimidine. This modification was employed to explore
      recognition by both purine and pyrimidine metabolizing enzymes. The synthesis of
      the carbocyclic fleximers and the results of their preliminary biological
      screening are described herein.

PMID- 24312723
TI  - From behavioural analyses to models of collective motion in fish schools.
AB  - Fish schooling is a phenomenon of long-lasting interest in ethology and ecology,
      widely spread across taxa and ecological contexts, and has attracted much
      interest from statistical physics and theoretical biology as a case of self
      organized behaviour. One topic of intense interest is the search of specific
      behavioural mechanisms at stake at the individual level and from which the school
      properties emerges. This is fundamental for understanding how selective pressure
      acting at the individual level promotes adaptive properties of schools and in
      trying to disambiguate functional properties from non-adaptive epiphenomena.
      Decades of studies on collective motion by means of individual-based modelling
      have allowed a qualitative understanding of the self-organization processes
      leading to collective properties at school level, and provided an insight into
      the behavioural mechanisms that result in coordinated motion. Here, we emphasize
      a set of paradigmatic modelling assumptions whose validity remains unclear, both
      from a behavioural point of view and in terms of quantitative agreement between
      model outcome and empirical data. We advocate for a specific and biologically
      oriented re-examination of these assumptions through experimental-based
      behavioural analysis and modelling. 

PMID- 24312724
TI  - Criticality and the onset of ordering in the standard Vicsek model.
AB  - Experimental observations of animal collective behaviour have shown stunning
      evidence for the emergence of large-scale cooperative phenomena resembling phase
      transitions in physical systems. Indeed, quantitative studies have found scale
      free correlations and critical behaviour consistent with the occurrence of
      continuous, second-order phase transitions. The standard Vicsek model (SVM), a
      minimal model of self-propelled particles in which their tendency to align with
      each other competes with perturbations controlled by a noise term, appears to
      capture the essential ingredients of critical flocking phenomena. In this paper,
      we review recent finite-size scaling and dynamical studies of the SVM, which
      present a full characterization of the continuous phase transition through
      dynamical and critical exponents. We also present a complex network analysis of
      SVM flocks and discuss the onset of ordering in connection with XY-like spin
      models. 

PMID- 24312725
TI  - Spatially balanced topological interaction grants optimal cohesion in flocking
      models.
AB  - Models of self-propelled particles (SPPs) are an indispensable tool to
      investigate collective animal behaviour. Originally, SPP models were proposed
      with metric interactions, where each individual coordinates with neighbours
      within a fixed metric radius. However, recent experiments on bird flocks indicate
      that interactions are topological: each individual interacts with a fixed number
      of neighbours, irrespective of their distance. It has been argued that
      topological interactions are more robust than metric ones against external
      perturbations, a significant evolutionary advantage for systems under constant
      predatory pressure. Here, we test this hypothesis by comparing the stability of
      metric versus topological SPP models in three dimensions. We show that
      topological models are more stable than metric ones. We also show that a
      significantly better stability is achieved when neighbours are selected according
      to a spatially balanced topological rule, namely when interacting neighbours are
      evenly distributed in angle around the focal individual. Finally, we find that
      the minimal number of interacting neighbours needed to achieve fully stable
      cohesion in a spatially balanced model is compatible with the value observed in
      field experiments on starling flocks. 

PMID- 24312726
TI  - Schools of fish and flocks of birds: their shape and internal structure by self
      organization.
AB  - Models of self-organization have proved useful in revealing what processes may
      underlie characteristics of swarms. In this study, we review model-based
      explanations for aspects of the shape and internal structure of groups of fish
      and of birds travelling undisturbed (without predator threat). Our models
      attribute specific collective traits to locomotory properties. Fish slow down to
      avoid collisions and swim at a constant depth, whereas birds fly at low
      variability of speed and lose altitude during turning. In both the models of fish
      and birds, the 'bearing angle' to the nearest neighbour emerges as a side-effect
      of the 'blind angle' behind individuals and when group size becomes larger,
      temporary subgroups may increase the complexity of group shape and internal
      structure. We discuss evidence for model-based predictions and provide a list of
      new predictions to be tested empirically. 

PMID- 24312727
TI  - A spatially explicit Bayesian framework for cognitive schooling behaviours.
AB  - Social aggregations such as schools, swarms, flocks and herds occur across a
      broad diversity of animal species, strongly impacting ecological and evolutionary
      dynamics of these species and their predators, prey and competitors. The
      mechanisms through which individual-level responses to neighbours generate group
      level characteristics have been extensively investigated both experimentally and
      using mathematical models. Models of social groups typically adopt a 'zone'
      approach, in which individuals' movement responses to neighbours are functions of
      instantaneous relative position. Empirical studies have demonstrated that most
      social animals such as fish exhibit well-developed spatial memory and other
      advanced cognitive capabilities. However, most models of social grouping do not
      explicitly include spatial memory, largely because a tractable framework for
      modelling acquisition of and response to historical spatial information has been
      lacking. Using fish schooling as a focal example, this study presents a framework
      for including cognitive responses to spatial memory in models of social
      aggregation. The framework utilizes Bayesian estimation parameters that are
      continuously distributed in time and space as proxies for animals' spatial
      memory. The result is a hybrid Lagrangian-Eulerian model in which the effects of
      cognitive state and behavioural responses to historical spatial data on
      individual-, group- and population-level distributions of social animals can be
      explicitly investigated. 

PMID- 24312728
TI  - Swarming and pattern formation due to selective attraction and repulsion.
AB  - We discuss the collective dynamics of self-propelled particles with selective
      attraction and repulsion interactions. Each particle, or individual, may respond
      differently to its neighbours depending on the sign of their relative velocity.
      Thus, it is able to distinguish approaching (coming closer) and retreating
      (moving away) individuals. This differentiation of the social response is
      motivated by the response to looming visual stimuli and may be seen as a
      generalization of the previously proposed escape and pursuit interactions
      motivated by empirical evidence for cannibalism as a driving force of collective
      migration in locusts and Mormon crickets. The model can account for different
      types of behaviour such as pure attraction, pure repulsion or escape and pursuit,
      depending on the values (signs) of the different response strengths. It provides,
      in the light of recent experimental results, an interesting alternative to
      previously proposed models of collective motion with an explicit velocity
      alignment interaction. We discuss the derivation of a coarse-grained description
      of the system dynamics, which allows us to derive analytically the necessary
      condition for emergence of collective motion. Furthermore, we analyse
      systematically the onset of collective motion and clustering in numerical
      simulations of the model for varying interaction strengths. We show that
      collective motion arises only in a subregion of the parameter space, which is
      consistent with the analytical prediction and corresponds to an effective escape
      and/or pursuit response. 

PMID- 24312729
TI  - Using field data to test locust migratory band collective movement models.
AB  - Wingless locust nymphs can form massive migratory groups known as bands, whose
      coordinated movement results from local interactions. We analysed the spatial
      distribution of locusts within naturally occurring bands and compared them with
      computer simulations to infer which interaction rules are used by individuals. We
      found that the empirical radial distribution of neighbours around a focal
      individual was isotropic, indicating a tendency for locusts to interact with
      neighbours all around them, rather than a bias towards pursuing individuals ahead
      or escaping from the ones following behind. By using maps of neighbour densities
      and pair correlation functions, we found evidence for a short-range repulsion
      force, balanced by a clustering force, presumably alignment and/or attraction, at
      a distance of around 3 cm. These results were similar to those observed when
      using a 'zonal' self-propelled particles model where
      repulsion/alignment/attraction forces are delimited by concentric circular zones
      of set radii. However, the profiles obtained either by using different
      combinations of forces, limiting the number of neighbours involved in
      interactions, or by varying the range of some zones, all appeared to produce
      similar results, thereby limiting the ability to more precisely determine the
      rules underlying locust interactions. 

PMID- 24312730
TI  - Pattern-formation mechanisms in motility mutants of Myxococcus xanthus.
AB  - Formation of spatial patterns of cells is a recurring theme in biology and often
      depends on regulated cell motility. Motility of the rod-shaped cells of the
      bacterium Myxococcus xanthus depends on two motility machineries, type IV pili
      (giving rise to S-motility) and the gliding motility apparatus (giving rise to A
      motility). Cell motility is regulated by occasional reversals. Moving M. xanthus
      cells can organize into spreading colonies or spore-filled fruiting bodies,
      depending on their nutritional status. To ultimately understand these two pattern
      formation processes and the contributions by the two motility machineries, as
      well as the cell reversal machinery, we analyse spatial self-organization in
      three M. xanthus strains: (i) a mutant that moves unidirectionally without
      reversing by the A-motility system only, (ii) a unidirectional mutant that is
      also equipped with the S-motility system, and (iii) the wild-type that, in
      addition to the two motility systems, occasionally reverses its direction of
      movement. The mutant moving by means of the A-engine illustrates that collective
      motion in the form of large moving clusters can arise in gliding bacteria owing
      to steric interactions of the rod-shaped cells, without the need of invoking any
      biochemical signal regulation. The two-engine strain mutant reveals that the same
      phenomenon emerges when both motility systems are present, and as long as cells
      exhibit unidirectional motion only. From the study of these two strains, we
      conclude that unidirectional cell motion induces the formation of large moving
      clusters at low and intermediate densities, while it results in vortex formation
      at very high densities. These findings are consistent with what is known from
      self-propelled rod models, which strongly suggests that the combined effect of
      self-propulsion and volume exclusion interactions is the pattern-formation
      mechanism leading to the observed phenomena. On the other hand, we learn that
      when cells occasionally reverse their moving direction, as observed in the wild
      type, cells form small but strongly elongated clusters and self-organize into a
      mesh-like structure at high enough densities. These results have been obtained
      from a careful analysis of the cluster statistics of ensembles of cells, and
      analysed in the light of a coagulation Smoluchowski equation with fragmentation. 

PMID- 24312731
TI  - Collective navigation of cargo-carrying swarms.
AB  - Much effort has been devoted to the study of swarming and collective navigation
      of micro-organisms, insects, fish, birds and other organisms, as well as multi
      agent simulations and to the study of real robots. It is well known that insect
      swarms can carry cargo. The studies here are motivated by a less well-known
      phenomenon: cargo transport by bacteria swarms. We begin with a concise review of
      how bacteria swarms carry natural, micrometre-scale objects larger than the
      bacteria (e.g. fungal spores) as well as man-made beads and capsules (for drug
      delivery). A comparison of the trajectories of virtual beads in simulations
      (using different putative coupling between the virtual beads and the bacteria)
      with the observed trajectories of transported fungal spores implies the existence
      of adaptable coupling. Motivated by these observations, we devised new, multi
      agent-based studies of cargo transport by agent swarms. As a first step, we
      extended previous modelling of collective navigation of simple bacteria-inspired
      agents in complex terrain, using three putative models of agent-cargo coupling.
      We found that cargo-carrying swarms can navigate efficiently in a complex
      landscape. We further investigated how the stability, elasticity and other
      features of agent-cargo bonds influence the collective motion and the transport
      of the cargo, and found sharp phase shifts and dual successful strategies for
      cargo delivery. Further understanding of such mechanisms may provide valuable
      clues to understand cargo-transport by smart swarms of other organisms as well as
      by man-made swarming robots. 

PMID- 24312733
TI  - Hypotensive and vasorelaxant effects of sericin-derived oligopeptides in rats.
AB  - Sericin-derived oligopeptides obtained from silk cocoons were investigated for
      the in vivo hypotensive effect and investigated for the underlying mechanism
      involved in vasodilation in isolated rat thoracic aorta. In normotensive
      anesthetized rats, oligopeptides induced an immediate and transient hypotensive
      activity. In rat aortic rings, oligopeptides induced a concentration-dependent
      vasorelaxation in vessels precontracted with both KCl and phenylephrine (PE) with
      endothelium-intact or endothelium-denuded rings. In endothelium-intact rings,
      pretreatment with N omega -Nitro-L-arginine methyl ester hydrochloride (L-NAME,
      100 uM), an inhibitor of the NO synthase (NOS) or 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ, 1 uM), a selective inhibitor of the guanylyl cyclase
      enzyme, significantly reduced the relaxant effect of oligopeptides. However,
      indomethacin, an inhibitor of the cyclooxygenase, had no effect on oligopeptides
      induced relaxation. In addition, pretreatment with tetraethylammonium (TEA, 5 mM)
      reduced the maximal relaxant effect induced by oligopeptides. By contrast,
      relaxation was not affected by 4-aminopyridine (4-AP, 1 mM), glibenclamide (10
      uM), or barium chloride (BaCl2, 1 mM). In depolarization Ca(2+)-free solution,
      oligopeptides inhibited calcium chloride- (CaCl2-) induced contraction in
      endothelium-denuded rings in a concentration-dependent manner. Nevertheless,
      oligopeptides attenuated transient contractions in Ca(2+)-free medium containing
      EGTA (1 mM) induced by 1 uM PE, but they were not affected by 20 mM caffeine. It
      is obvious that potent vasodilation effect of oligopeptides is mediated through
      both the endothelium and the vascular smooth muscle. 

PMID- 24312735
TI  - Periodontal plastic microsurgery in the treatment of deep gingival recession
      after orthodontic movement.
AB  - Gingival recession is a condition that affects a large portion of the young and
      adult population and negatively affects the aesthetic aspects of the smile. Many
      factors are related to its development, including orthodontic movement beyond the
      osseous limits. Many treatment options have been proposed to cover the exposed
      root surface. The aim of this article was to describe three cases where a
      subepithelial connective tissue graft was performed, using a microsurgical
      technique, in the treatment of deep gingival recession after orthodontic
      treatment. This technique resulted in successful root coverage and keratinized
      tissue gain, improving the gingival esthetic pattern. 

PMID- 24312734
TI  - Comparative morphology of dendritic arbors in populations of Purkinje cells in
      mouse sulcus and apex.
AB  - Foliation divides the mammalian cerebellum into structurally distinct
      subdivisions, including the concave sulcus and the convex apex. Purkinje cell
      (PC) dendritic morphology varies between subdivisions and changes significantly
      ontogenetically. Since dendritic morphology both enables and limits sensory-motor
      circuit function, it is important to understand how neuronal architectures differ
      between brain regions. This study employed quantitative confocal microcopy to
      reconstruct dendritic arbors of cerebellar PCs expressing green fluorescent
      protein and compared arbor morphology between PCs of sulcus and apex in young and
      old mice. Arbors were digitized from high z-resolution (0.25 um) image stacks
      using an adaptation of Neurolucida's (MBF Bioscience) continuous contour tracing
      tool, designed for drawing neuronal somata. Reconstructed morphologies reveal
      that dendritic arbors of sulcus and apex exhibit profound differences. In sulcus,
      72% of the young PC population possesses two primary dendrites, whereas in apex,
      only 28% do. Spatial constraints in the young sulcus cause significantly more
      dendritic arbor overlap than in young apex, a distinction that disappears in
      adulthood. However, adult sulcus PC arbors develop a greater number of branch
      crossings. These results suggest developmental neuronal plasticity that enables
      cerebellar PCs to attain correct functional adult architecture under different
      spatial constraints. 

PMID- 24312732
TI  - Autoimmune T-cell reactivity to myelin proteolipids and glycolipids in multiple
      sclerosis.
AB  - Central nervous system (CNS) myelin, the likely major target of autoimmune attack
      in multiple sclerosis (MS), contains a number of unique components that are
      potential targets of the attack. Two classes of molecules that are greatly
      enriched in CNS myelin compared to other parts of the body are certain types of
      proteolipids and glycolipids. Due to the hydrophobic nature of both of these
      classes of molecules, they present challenges for use in immunological assays and
      have therefore been somewhat neglected in studies of T-cell reactivity in MS
      compared to more soluble molecules such as the myelin basic proteins and the
      extracellular domain of myelin oligodendrocyte glycoprotein. This review firstly
      looks at the makeup of CNS myelin, with an emphasis on proteolipids and
      glycolipids. Next, a retrospective of what is known of T-cell reactivity directed
      against proteolipids and glycolipids in patients with MS is presented, and the
      implications of the findings are discussed. Finally, this review considers the
      question of what would be required to prove a definite role for autoreactivity
      against proteolipids and glycolipids in the pathogenesis of MS. 

PMID- 24312736
TI  - A case of erythrocytosis in a patient treated with an aromatase inhibitor for
      breast cancer.
AB  - A previously healthy 79-year-old female was referred to hematology for further
      evaluation of erythrocytosis. Two years earlier she had been diagnosed with ER/PR
      positive ductal carcinoma of the breast and was receiving hormonal therapy with
      exemestane. No secondary cause of erythrocytosis was identified. Serum
      erythropoietin (EPO) level was normal, and molecular testing for the JAK2 V617F
      and exon 12 mutations was negative. A bone marrow biopsy showed a mild increase
      in erythropoiesis, and no spontaneous erythroid colonies were demonstrated.
      Erythrocytosis is common reason for referral to a hematologist. The
      myeloproliferative disorder, polycythemia vera, and the rare congenital
      polycythemias represent primary erythrocytosis. Common secondary causes include
      smoking, obstructive sleep apnea, and other pulmonary diseases. Erythrocytosis is
      well described with certain classes of drugs, including androgens. We hypothesize
      that exemestane contributed to the development of erythrocytosis in our patient.
      To our knowledge, erythrocytosis has not been previously described in association
      with aromatase inhibitors. These drugs prevent the conversion of androstenedione
      and testosterone to estrogen; thus the physiologic mechanisms may be similar to
      those responsible for erythrocytosis seen with exogenous androgens. These
      mechanisms are not well understood, but may include altered iron metabolism by a
      reduction in hepcidin levels. 

PMID- 24312737
TI  - Lupus nephritis in a patient with sickle cell disease.
AB  - Introduction. The diagnosis of systemic lupus erythematosus (SLE) in patients
      with sickle cell disease (SCD) can be difficult to establish because the
      musculoskeletal, central nervous system, and renal manifestations are similar in
      both diseases. In the presented case, we highlight the diagnostic challenge that
      can evolve in patients with a concurrence of both diseases and we establish the
      importance of early recognition and treatment of lupus nephritis in patients with
      SCD. Case Presentation. We present a case of a 31-year-old African American
      female with sickle-C disease (hemoglobin SC) who was admitted to our hospital
      with complaints of periumbilical abdominal pain associated with intractable
      nausea and vomiting, abdominal distension, and worsening lower extremity edema.
      Urine studies revealed nephrotic range proteinuria and the immunological
      investigations were consistent with lupus. A renal biopsy revealed focal
      proliferative lupus nephritis. Conclusion. It is important to consider the
      presence of a coexisting autoimmune disease in a patient with sickle
      hemoglobinopathy who displays an atypical and multisystem presentation that is
      unresponsive to conventional therapies. When a significant kidney disease is
      present, a renal biopsy is critical in identifying the etiology of a renal
      abnormality in the setting of coexisting SLE and SCD. 

PMID- 24312738
TI  - A case of recurrent mesocolon myxoid liposarcoma and review of the literature.
AB  - Background. Liposarcoma is the second most common soft tissue sarcoma affecting
      predominantly the retroperitoneal space and extremities. Mesenteric liposarcoma
      is uncommon and occurs in the small bowel mesentery. In this paper we report the
      case of a recurrent mesocolon myxoid liposarcoma manifesting 6 years from the
      initial right hemicolectomy for the primary tumour. Case Report. A 41-year-old
      female presented with a 4-day history of signs and symptoms indicative of small
      bowel obstruction, subsequently confirmed on plain abdominal X-ray. In 2006 she
      underwent a right hemicolectomy for a myxoid liposarcoma of the mesentery. The
      patient was initially managed conservatively; however she showed no signs of
      improvement and was taken to theatre for an exploratory laparotomy and division
      of adhesional bands. During this procedure an incidental finding of a dark
      purple, smooth pelvic mass was identified with similar macroscopic appearance to
      that of splenic tissue. Histological examination revealed a recurrent mesocolon
      myxoid liposarcoma. Conclusion. Mesocolon myxoid liposarcoma is a rare soft
      tissue neoplastic pathology and carries a high risk of recurrence. Therefore, a
      symptomatic patient with a previous history of primary liposarcoma excision
      should be treated with a high index of suspicion and a longer period of followup
      should be considered. 

PMID- 24312739
TI  - A reclusive foreign body in the airway: a case report and a literature review.
AB  - A foreign body in the larynx is an airway emergency that requires urgent
      evaluation and treatment. Irregular foreign bodies tend to orient in a sagittal
      plane and may produce only partial obstruction, allowing adequate air movement,
      hence making them undetectable for a long period of time. We report a case of a
      laryngotracheal foreign body that remained reclusive for 9 years. 

PMID- 24312740
TI  - First branchial cleft malformation with duplication of external auditory canal.
AB  - First branchial cleft anomalies are uncommon, accounting for less than 10% of all
      branchial abnormalities. Their rare occurrence and varied presentation have
      frequently led to misdiagnosis and inadequate and inappropriate treatment of
      these conditions leading to repeated recurrences and secondary infection. In this
      paper, a case of 11-year girl with type 2 first branchial cleft defect is
      described. She first presented with a nonhealing ulcer of upper neck from
      childhood. Diagnosis had previously been missed and treated as tubercular ulcer.
      We confirmed the correct diagnosis by history and computerized tomography
      fistulogram. The lesion was completely excised with no further recurrence. 

PMID- 24312741
TI  - Acute appendicitis complicated by pylephlebitis: a case report.
AB  - Pylephlebitis is defined as septic thrombophlebitis of the portal vein. It is a
      rare but serious complication of an intraabdominal infection, more commonly
      diverticulitis and appendicitis. It has an unspecific clinical presentation and
      the diagnosis is difficult. The authors report a case of a 21-year-old man with
      acute appendicitis complicated by pylephlebitis. The diagnosis was made with
      contrast enhanced CT. 

PMID- 24312743
TI  - Erratum: Investigation of depth-resolved nanoscale structural changes in
      regulated cell proliferation and chromatin decondensation: erratum.
AB  - We correct minor errors in two equations reported in our paper [Biomed. Opt.
      Express 4, 596-613 (2013)]; an additional factor of two was mistakenly
      incorporated in Eqs. (3) and (4). We give the correct equations below. All the
      simulations and experiments in the previous paper were performed using the
      correct equations, and therefore, remain the same.[This corrects the article on
      p. 596 in vol. 4, PMID: 23577294.].

PMID- 24312744
TI  - Variational analysis of the mouse and rat eye optical parameters.
AB  - Rodent models are increasingly used to study refractive eye development and
      development of refractive errors; however, there is still some uncertainty
      regarding the accuracy of the optical models of the rat and mouse eye primarily
      due to high variability in reported ocular parameters. In this work, we have
      systematically evaluated the contribution of various ocular parameters, such as
      radii of curvature of ocular surfaces, thicknesses of ocular components, and
      refractive indices of ocular refractive media, using variational analysis and a
      computational model of the rodent eye. Variational analysis revealed that not all
      variation in ocular parameters has critical impact on the refractive status of
      the eye. Variation in the depth of the vitreous chamber, thickness of the lens,
      radius of the anterior surface of the cornea, radius of the anterior surface of
      the lens, as well as refractive indices for the lens and vitreous, appears to
      have the largest impact on the refractive error. The radii of the posterior
      surfaces of the cornea and lens have much smaller contributions to the refractive
      state. These data provide the framework for further refinement of the optical
      models of the rat and mouse eye and suggest that extra efforts should be directed
      towards increasing the linear resolution of the rodent eye biometry and obtaining
      more accurate data for the refractive indices of the lens and vitreous. 

PMID- 24312745
TI  - Importance of Smoking Cessation in a Lung Cancer Screening Program.
AB  - Early detection of lung cancer and smoking cessation interventions can decrease
      lung cancer mortality, but information on the effectiveness and interaction
      between smoking cessation and lung cancer screening is sparse and inconsistent.
      This review aims to synthesize recent studies in two major areas of interest.
      First, we explore the interactions and potential for synergies between lung
      cancer screening programs and smoking cessation by summarizing reported changes
      in smoking behavior observed in major screening trials in the United States and
      Europe, as well as attempts to use smoking cessation interventions to augment the
      benefits from lung cancer screening programs. Second, we review the interaction
      between smoking habits and pre/post-operative pulmonary resection outcomes,
      including changes in smoking behavior post-diagnosis and post-treatment.
      Information from these areas should allow us to maximize benefits from smoking
      cessation interventions through the entire lung cancer screening process, from
      the screen itself through potential curative resection after diagnosis.

PMID- 24312746
TI  - Concise set of files for smooth return to work in employees with mental
      disorders.
AB  - Sick leave due to mental disorders is a societal problem. It carries a high cost
      in terms of loss of labor productivity and absenteeism. Partial remission
      increases the risk of relapse after a return to work. There is sometimes a
      difference between the ability to return to work as judged by a general
      practitioner (GP) and the needs of the workplace. GPs are the main controllers of
      treatment and tend to protect their patients. Communication and agreement by GPs
      and occupational physicians play an effective role in the return to work.
      However, it requires considerable effort for both of them to make time to do
      this. We have developed a concise set of files for a smooth return to work. The
      files consist of three parts: "Suggestions for corresponding with employees
      taking sick leave"; "Checklist for smooth return to work"; and "Pattern of
      living". We put them into practice among 20 companies in Japan from January 2012
      to October 2013. The companies had 8244 workers in total and 116 workers were on
      sick-leave due to mental disorders. Our set of files contributed to sharing the
      written basic policy of return to work among employees on sick leave with mental
      disorders, GPs, occupational physicians and personnel officers. That sharing led
      to facilitating a smooth return to work. Although there are differences in the
      legal and medical systems between Japan and other countries, our concept of
      sharing the written basic policy may give some help to occupational physicians in
      other parts of the world as well. 

PMID- 24312747
TI  - Cystine and theanine: amino acids as oral immunomodulative nutrients.
AB  - The decreases in the glutathione (GSH) level in the mouse spleen and liver after
      immune stimulation are suppressed by the oral administration of cystine and
      theanine (CT). GSH is considered to be important for the control of immune
      responses. Antibody production in mice after infection is enhanced by the oral
      administration of CT. In humans, also, the oral administration of CT has been
      confirmed to enhance antibody production after vaccination against Flu and also
      reduce the incidence of cold. However, the GSH level is reduced by intense
      exercise and surgery. In clinical studies of body-builders and long-distance
      runners, the intake of CT suppressed excessive inflammatory reactions and a
      decline in immune functions after intense training. Surgery as well as intense
      exercise induces excessive inflammatory reactions. In mice, the preoperative
      administration of CT suppressed excessive inflammatory reactions associated with
      surgery and promoted the postoperative recovery. Moreover, in clinical studies of
      gastrectomized patients, CT intake suppressed excessive postoperative
      inflammatory reactions and induced early recovery. If infection is regarded as
      invasive stress, CT intake is considered to exhibit an immunomodulatory effect by
      suppressing the decrease in GSH due to invasive stress. The clarification of
      their detailed action mechanisms and their application as medical or function
      foods is anticipated. 

PMID- 24312748
TI  - Lying down with protective setae as an alternative antipredator defence in a non
      webbing spider mite.
AB  - An antipredator defence in the citrus red mite Panonychus citri, which does not
      produce protective webs, was examined experimentally. P. citri adult females lie
      down on citrus leaf surfaces with their dorsal setae (hair) directed in all upper
      directions. They seldom move in response to physical stimuli. Compared to normal
      lying females, both manipulated non-lying females and hair-removed females
      suffered higher predation by predatory mites. A predator approaching the body
      surface of a lying female inevitably created elasticity with a confronting seta,
      which eventually repelled the predator away from the female. These observations
      indicated that lying down with protective setae functions as an antipredator
      defence in P. citri females. This inflexible defence could also explain why the
      mite rarely runs away, even when it is consumed together with host plant leaves
      (via coincidental intraguild predation) by gigantic swallowtail caterpillars,
      against which protective setae are totally ineffective. 

PMID- 24312750
TI  - Synthesis of Novel 1,4- Dihydropyridine Derivatives Bearing Biphenyl-2'-Tetrazole
      Substitution as Potential Dual Angiotensin II Receptors and Calcium Channel
      Blockers.
AB  - INTRODUCTION: We report the synthesis of novel 1,4-dihydropyridine derivatives
      containing biphenyl-2'-tetrazole moieties. We hypothesized that merging the key
      structural elements present in an AT1 receptor antagonist with key structural
      elements in 1,4-dihydropyridine calcium channel blockers would yield novel
      analogs with potential dual activity for both receptors. This strategy led to the
      design and synthesis of dialkyl 1,4-dihydro-2,6-dimethyl-4-[2-n-alkyl-1-[2?-(1H
      tetrazole-5-yl) biphenyl -4-yl] methyl] imidazole-4(or 5)-yl]- 3, 5
      pyridinedicarboxylate analogs. METHODS: These compounds were obtained by two
      methods starting from biphenyltetrazolyl-4-(or 5)-imidazolecarboxaldehyde
      intermediates employing in classical Hantzsch condensation reaction. In the first
      method, triphenylmethyl protecting group of 4- or 5-carboxaldehyde intermediate
      was first removed in acidic media and then classical Hantzsch reaction was
      employed in order to obtain the final products. In the second method, without
      further deprotection process, protected 4- or 5-carboxaldehyde intermediate
      directly was used in Hantzsch reaction. RESULTS: The second method was more
      efficient than the first method since the deprotection and ring closure reaction
      occurs simultaneously in one pot. CONCLUSION: Eight novel dihydropridines analogs
      were synthesized using classic Hantzsch condensation reaction. Chemical
      structures of the compounds were characterized by (1)H NMR, infrared and mass
      spectroscopy.

PMID- 24312749
TI  - Therapeutic actions of melatonin on gastrointestinal cancer development and
      progression.
AB  - Melatonin exerts a multitude of physiological functions including the regulation
      of the sleep cycle and circadian rhythm. Although the synthesis of melatonin in
      the pineal gland is regulated by changes in the light/dark cycle, the release of
      melatonin in the gastrointestinal tract is related to food consumption. Melatonin
      regulates antioxidative processes and it improves T-helper cell response by
      stimulating the production of specific cytokines. Melatonin is directly involved
      in preventing tumor initiation, promotion, and progression in a variety of
      cancers of the gastrointestinal tract including colorectal cancer,
      cholangiocarcinoma, hepatocarcinoma, and pancreatic carcinoma. This paper is a
      review of the literature regarding melatonin in the gastrointestinal tract and as
      a potential therapy for gastrointestinal cancers.

PMID- 24312751
TI  - Vasorelaxant Effect of a Newly Synthesized Dihydropyridine Ethyl Ester (DHPEE) on
      Rat Thoracic Aorta: Dual Mechanism of Action.
AB  - INTRODUCTION: DHPEE is a newly synthesized compound by merging the key structural
      elements in an angiotensin receptor blocker (Telmisartan) with key structural
      elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine). In this
      study, we examined dual calcium channel blocking and AT1 antagonist activity for
      DHPEE. METHODS: The functional inhibitory characteristics of DHPEE were studied
      in vitro in rat thoracic aorta preparations precontracted by phenylephrine (1MUM)
      or KCl (80MUM) or Ang II in normal or calcium-free solutions. RESULTS:
      Concentration-dependent significant relaxation was observed in aortic rings
      precontracted with phenylephrine, KCl or Ang II. The tension increment produced
      by increasing external calcium was also reduced by DHPEE. DHPEE caused a marked
      decrease in the maximal contractile response of the vasoactive agents and shifted
      their concentration-response curves to the right. CONCLUSION: DHPEE possesses
      dual characteristics and cause vasorelaxation by blocking the L-type calcium
      channels and blocking Ang II receptors (AT1) in rat aortic smooth muscle.

PMID- 24312752
TI  - Effects of process variables on micromeritic properties and drug release of non
      degradable microparticles.
AB  - INTRODUCTION: The purpose of this investigation was to evaluate microencapsulated
      controlled release preparation of theophylline using Eudragit RS 100 as the
      retardant material with high entrapment efficiency. METHODS: Microspheres were
      prepared by the emulsion-solvent evaporation method. A mixed solvent system
      consisting of methanol and acetone and light liquid paraffin as oily phase were
      chosen. Sucrose stearate was used as the surfactant to stabilize the
      emulsification process. The prepared microspheres were characterized by drug
      loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning
      colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release
      studies were performed at pH 1.2 and 7.4 aqueous medium. RESULTS: Increasing the
      concentration of emulsifier, sucrose fatty acid ester F-70, decreased the
      particle size which contributed to increased drug release rate. The drug loading
      microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle
      size 205.93-352.76 MUm.The results showed that, an increase in the ratio of
      polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug
      which may be attributed to the hydrophobic nature of the polymer. CONCLUSION: The
      release of theophylline is influenced by the drug to polymer ratio and particle
      size. Drug release is controlled by diffusion and the best-fit release kinetic is
      Higuchi model.

PMID- 24312753
TI  - Polymer Percolation Threshold in Multi-Component HPMC Matrices Tablets.
AB  - INTRODUCTION: The percolation theory studies the critical points or percolation
      thresholds of the system, where one component of the system undergoes a
      geometrical phase transition, starting to connect the whole system.The
      application of this theory to study the release rate of hydrophilic matrices
      allows to explain the changes in release kinetics of swellable matrix type system
      and results in a clear improvement of the design of controlled release dosage
      forms. METHODS: In this study, the percolation theory has been applied to multi
      component hydroxypropylmethylcellulose (HPMC) hydrophilic matrices. Matrix
      tablets have been prepared using phenobarbital as drug, magnesium stearate as a
      lubricant employing different amount of lactose and HPMC K4M as a filler and
      matrix forming material, respectively. Ethylcelullose (EC) as a polymeric
      excipient was also examined. Dissolution studies were carried out using the
      paddle method.In order to estimate the percolation threshold, the behaviour of
      the kinetic parameters with respect to thevolumetric fraction of HPMC at time
      zero, was studied. RESULTS: In both HPMC/lactose and HPMC/EC/lactose matrices,
      from the point of view of the percolation theory, the optimum concentration for
      HPMC, to obtain a hydrophilic matrix system for the controlled release of
      phenobarbital is higher than 18.1% (v/v) HPMC. Above 18.1% (v/v) HPMC, an
      infinite cluster of HPMC would be formed maintaining integrity of the system and
      controlling the drug release from the matrices. According to results, EC had no
      significant influence on the HPMC percolation threshold. CONCLUSION: This may be
      related to broad functionality of the swelling hydrophilic matrices.

PMID- 24312754
TI  - Simultaneous Determination of Tetracyclines Residues in Bovine Milk Samples by
      Solid Phase Extraction and HPLC-FL Method.
AB  - INTRODUCTION: Tetracyclines (TCs) are widely used in animal husbandry and their
      residues in milk may resultin harmful effects on human. The aim of this study was
      to investigate the presence of TCs residues in various bovine milk samples from
      local markets of Ardabil, Iran. METHODS: One hundred and fourteen pasteurized,
      sterilized and raw milk samples were collected from markets of Ardabil.
      Tetracycline, Oxytetracycline and Chlortetracycline (TCs) residues extraction
      carried out by Solid Phase Extraction method. Determination of TCs residues were
      performed by high performance liquid chromatography (HPLC) method using
      Fluorescence detector. RESULTS: The mean of total TCs residues in all samples
      (114 samples) was 97.6 +/-16.9ng/g and that of pasteurized, sterilized and raw
      milk samples were 87.1 +/- 17.7, 112.0 +/- 57.3 and 154.0 +/- 66.3ng/g
      respectively. Twenty five point four percent of the all samples, and 24.4%, 30%
      and 28.6% of the pasteurized, sterilized and raw milk samples, respectively had
      higher TCs residues than the recommended maximum levels (100ng/g). CONCLUSION:
      This study indicates the presence of tetracycline residues more than allowed
      amount. Regulatory authorities should ensure proper withdrawal period before
      milking the animals and definite supervisions are necessary on application of
      these drugs.

PMID- 24312755
TI  - Novel PH Sensitive Nanocarrier Agents Based on Citric Acid Dendrimers Containing
      Conjugated beta-Cyclodextrins.
AB  - INTRODUCTION: In this work, the use of beta-cyclodextrine (beta-CD)-modified
      dendrimers as a nanocapsule with a biocompatible shell have studied. beta-CD
      modifieddendrimers have designed and synthesized to enhance the loading capacity
      of the final dendrimers with encapsulation properties. METHODS: To achieve beta
      CD-modified dendrimers, first citric acid dendrimers were synthesized and then
      the end functional groups of dendrimers were grafted to beta-CD through ester
      linkages. The molecular structures of resulted dendrimers were verified using
      common spectroscopic methods such as 1H NMR, FT-IR and the diameters of obtained
      nanocarriers were evaluated with using dynamic light scattering (DLS)
      experiments. The isolated dendrimers were utilized as the drug delivery agents
      and the encapsulation and the controlled release of guest drug molecule
      Naltrexone (NLX) was investigated in different pH's using UV spectroscopy method.
      RESULTS: It was established that the loading capacity of dendrimers depend on
      several factors such as their generation and the structure and number of
      conjugated modifier end groups. CONCLUSION: Increasing in the number of branches
      and the size of interior voids and number of conjugated beta-CDs cause to enhance
      the loading capacity.

PMID- 24312756
TI  - Studies on dissolution enhancement of prednisolone, a poorly water-soluble drug
      by solid dispersion technique.
AB  - INTRODUCTION: Prednisolone is a class II substance according to the
      Biopharmaceutics Classification System. It is a poorly water soluble agent. The
      aim of the present study was to improve dissolution rate of a poorly water
      soluble drug, prednisolone, by a solid dispersion technique. METHODS: Solid
      dispersion of prednisolone was prepared with PEG 6000 or different carbohydrates
      such as lactose and dextrin with various ratios of the drug to carrier i.e.,
      1:10, 1:20 and 1:40. Solid dispersions were prepared by coevaporation method. The
      evaluation of the properties of the dispersions was performed using dissolution
      studies, Fourier-transform infrared spectroscopy and x-ray powder
      diffractometery. RESULTS: The results indicated that lactose is suitable carriers
      to enhance the in vitro dissolution rate of prednisolone. The data from the x-ray
      diffraction showed that the drug was still detectable in its solid state in all
      solid dispersions except solid dispersions prepared by dextrin as carrier. The
      results from infrared spectroscopy showed no well-defined drug-carrier
      interactions for coevaporates. CONCLUSION: Solid dispersion of a poorly water
      soluble drug, prednisolone may alleviate the problems of delayed and inconsistent
      rate of dissolution of the drug.

PMID- 24312757
TI  - Hollow microspheres for gastroretentive floating- pulsatile drug delivery:
      preparation and in vitro evaluation.
AB  - PURPOSE: A multiparticular floating-pulsatile drug delivery system was developed
      for time and site specific drug release of piroxicam. A blend of floating and
      pulsatile principles of drug delivery system would have the advantage that a drug
      can be released in the upper GI tract after a definite time period. METHODS:
      Hollow microspheres were prepared by the emulsion solvent diffusion method using
      Eudragit S as an enteric acrylic polymer with piroxicam at various polymer/drug
      ratios in a mixture of dichloromethane and ethanol. Developed formulations were
      evaluated for yield, encapsulation efficiency, particle size, shape, apparent
      density, buoyancy studies and dissolution studies. RESULTS: The obtained
      microballoons were spherical with no major surface irregularity and mean particle
      size ranging from 250 to 380 for different batches. Formulations show a slight
      amount of relaese ranging from 0.7 to 11% in acidic medium (SGF) with complete
      release of drug in simulated intestinal fluid (SIF) in less than 3 h.
      Encapsulation efficiency of different formulations varied from 90 to 98%. The
      optimum loading amount of drug in the particles was found to impart suitable
      floatable properties to the microballoons. With increasing polymer/drug ratio,
      buancy of the microballoons increases accompanied by simultaneous reduction of
      apparent particle density. CONCLUSION: A pulsatile release of piroxicam was
      demonstrated by a simple drug delivery system which could be useful in
      chronopharmacotherapy of rheumatoid arthritis.

PMID- 24312758
TI  - Phytochemical analysis and antioxidant activity of Hyssopus officinalis L. from
      Iran.
AB  - INTRODUCTION: Hyssopus officinalis (L) (Hyssop, Family: Lamiaceae), one of the
      endemic Iranian perennial herb with a long history of medicinal use, was studied
      to detect some biologically active chemical constituents of the plant. METHODS:
      The flavonoids of the hydromethanolic extract of the aerial parts of Hyssopus
      officinalis (L.) were studied by VLC and crystalisation of the major compound in
      subsequent fractions. Furthermore, the composition of its essential oil, total
      phenolic content and antioxidant activities were studied by GC-MS, Folin
      Ciocalteau and DPPH reagents respectively. RESULTS: Apigenin 7-O-beta-D
      glucuronide was isolated as the major flavonoid. All structural elucidation was
      performed by spectral means. A total of 20 compounds representing 99.97% of the
      oil have been identified. Myrtenylacetate, Camphor, Germacrene, Spathulenol were
      the main compounds The total phenol content of the n-butanol and ethylacetate
      extracts were determined spectrophotometrically according to the Folin-Ciocalteau
      procedure to be 246 mgGAE g(-1) and 51 mgGAE g(-1) in the aerial parts of
      Hyssopus officinalis . The antioxidant activities of apigenin 7-O-beta-D
      glucuronide, ethylacetate and n-butanol extracts were also determined by DPPH
      radical scavenging assay with IC50 values of 116*10(-3), 103*10(-3), 25*10(-3) mg
      mL(-1) respectively. The purified flavonoid showed weak radical scavenging
      activity (IC50 = 116*10(-3)mg mL(-1)). N-butanol extract, because of the highest
      content of total phenolic compounds (246 mgGAE100(-1)g) had the best antioxidant
      activity (IC50 = 25mg mL(-1)). CONCLUSION: On the whole, the findings of the
      study revealed that Hyssop possesses valuable antioxidant properties for culinary
      and possible medicinal use.

PMID- 24312759
TI  - Effect of Taurine on the antimicrobial efficiency of Gentamicin.
AB  - CONTEXT: Gentamicin is mainly used in severe infections caused by gram-negatives.
      However toxicity including nephrotoxicity and ototoxicity is one of the most
      important complications of its treatment. The production of free radicals seems
      to be involved in gentamicin toxicity mechanism. Taurine, a major intracellular
      free beta-amino acid, is known to be an endogenous antioxidant. So potentially
      the co-therapy of taurine and gentamicin would reduce the adverse effects of the
      antibiotic. OBJECTIVES: In this study, we wished to know the effect of taurine on
      the antibiotic capacity of gentamicin. METHODS: strainsof P. aeruginosa, E. coli,
      S. aureus and S. epidermidis were used as test organisms. Minimum inhibitory
      concentrations of gentamicin in the presence and absence of taurine at quantities
      from 40 to 2 mg/L were determined using macro-dilution method. RESULTS: MICs were
      determined in the various concentrations of taurine for bacterial indicators. The
      MIC values of gentamicin for P. aeruginosa, S. aureus and E. coli remained
      unchanged in the values of 2.5, 5 and 20 MUg/ml respectively in the absence and
      presences of different concentrations of taurine. The bactericidal activity of
      gentamicin against S. epidermidis was increased by addition of taurine in the
      concentrations higher than 6 mg/L. CONCLUSION: According to our study the
      antibacterial activity of gentamicin against the indicator microorganisms were
      not interfere with taurine at selected concentrations. Further in vivo studies
      are needed to establish if a combination of gentamicin and taurine would have the
      same effect.

PMID- 24312760
TI  - Determination of comparative minimum inhibitory concentration (MIC) of
      bacteriocins produced by enterococci for selected isolates of multi-antibiotic
      resistant Enterococcus spp.
AB  - INTRODUCTION: The occurrence of multi-antibiotic resistance among enterococci is
      a prevalent clinical problem worldwide and continues to get serious due to the
      lack of efficient therapeutic options by the time. In this regards, prokaryotic
      antimicrobial peptides with bactericidal or bacteriostatic activity which are
      directed against bacterial strains closely related to producer strains looks one
      of the promising alternative to conventional antibiotics. METHODS: The antibiotic
      susceptibility pattern of 20 clinical isolates of enterococci was evaluated and
      subsequently the isolates were screened for antibacterial activity against three
      different indicator strains. The efficacy of potential bacteriocinogenic isolates
      were assayed against multi-antibiotic resistant Enterococcus spp. by comparative
      minimum inhibitory concentration (MIC). RESULTS: Antibiotic resistant pattern of
      enterococcal isolates demonstrated that multi-antibiotic resistant to
      conventional antibiotics were significantly high and the prevalent pattern of
      resistance was combination of gentamicin, streptomycin, chloramphenicol and
      vancomycin. In addition, the data from comparative MIC showed the noticeable
      activity of selected potential bacteriocinogenic strains against pathogenic
      enterococci. CONCLUSION: The present survey may address the potential
      applicability of antimicrobial peptides in alleviating the problems of antibiotic
      resistance.

PMID- 24312761
TI  - Comparison of effect of resveratrol and vanadium on diabetes related dyslipidemia
      and hyperglycemia in streptozotocin induced diabetic rats.
AB  - PURPOSE: Resveratrol a natural polyphenolicstilbene derivative has wide variety
      of biological activities. There is also a large body of evidence demonstrating
      positive effect of resveratrol in treatment of various metabolic complications
      including metabolic syndrome, obesity, diabetes and dyslipidemia in adults. The
      purpose of this study was to investigate anti-hyperglycemic and anti-dyslipidemic
      effects of resveratrol. METHODS: We used 40 diabetic streptozotocin Wistar rats.
      Rats were randomly divided into 5 treatment groups (n=8 in each) including normal
      control, normal treated with resveratrol, diabetic control, diabetic treated with
      vanadium , diabetic treated with resveratrol . Resveratrol (25 mg/kgbw) and
      vanadate (0.2 mg/kgbw) was orally gavaged for 40 days and blood samples were
      directly collected from heart. RESULTS: Diabetic rats treated with resveratrol in
      comparison to control diabetic rats demonstrated a significant (p = 0.001)
      decline in serum glucose concentration, and high plasma concentrations of total
      cholesterol and LDL-c were reduced (p = 0.031, p = 0.004 respectively).
      Furthermore, body weight loss trend that observed in diabetic rats alleviated by
      resveratrol and vanadate. However triglyceride, VLDL-c and HDL-c levels did not
      changed significantly. CONCLUSION: In conclusion Resveratrol ameliorated
      dyslipidemia and hyperglycemia in diabetic rats. However further investigations
      in peculiar human studies are required.

PMID- 24312762
TI  - Preparation and In vitro Investigation of Chitosan Compressed Tablets for Colon
      Targeting.
AB  - PURPOSE: The aim of the present study was minimizing the drug release in upper
      gastro intestinal tract and targeting to colon by using the principles of
      compression coat. METHODS: Compression coated tablets of Ibuprofen were prepared
      by direct compression method using chitosan (300, 250, 200 & 175 mg). Tablets
      were evaluated for their physicochemical properties and in vitro drug release
      studies. In vitro drug release studies were performed with and without rat caecal
      contents. RESULTS: In the rat caecal contents tablets showed enhanced drug
      release due to degradation of chitosan coat by colonic colonic enzymes. The in
      vitro release studies in pH-6.8 phosphate buffer containing 2% w/v of rat caecal
      contents showed the cumulative percentage release of Ibuprofen after 26h as
      31.94% +/-0.59, 67.89% +/- 0.45 and 55.87 % +/- 0.45 and 82.52 % +/- 0.92
      respectively. Coat thickness and amount of chitosan controls the release rate.
      Formulations are best fitted with Korsmeyer-Peppas kinetics and mechanism of drug
      release was non-Fickian. FTIR studies reveals there is no drug-polysaccharide
      interaction. F1 formulation was a promising system for drug targeting to colon.
      CONCLUSION: Based on the obtained results chitosan as a press coat could target
      ibuprofen to the colon.

PMID- 24312763
TI  - Formulation of cefuroxime axetil oral suspension and investigation of its
      pharmaceutical properties.
AB  - PURPOSE: Cefuroxime is the second generation cephalosporin, which its intravenous
      and oral dosage forms are available. Oral route is the selective method for
      administration of most of the drugs. The aim of this study was formulating 'for
      oral' cefuroxime axetil suspensions. METHODS: Minitab (ver.15) was used to design
      the formulations containing 125 mg of cefuroxime in 5 ml vehicle. After selecting
      the acceptable preparations, physical stability tests and other tests such as
      dissolution rate, pH, zeta potential and viscosity measurement of formulations
      were performed. RESULTS: From all 33 formulations, only 9 were selected to
      further investigation. Considering no sedimentation, the sedimentation volume was
      determined to be 1. The degrees of flocculation were also equal to 1. All
      selected formulations released the drug between 81-100% in 30 minutes which was
      acceptable according to the USP32 criteria. The results of assay test also proved
      that all formulations contain the drug in acceptable range (91-106%). The
      viscosity curves showed that the systems were pseudo plastic and thixotrop.
      CONCLUSION: Designed cefuroxime axetil formulations had good qualities and could
      be added as a new product to Iran drug marketing.

PMID- 24312764
TI  - Modulating effect of Allium cepa on kidney apoptosis caused by Toxoplasma gondii.
AB  - PURPOSE: Toxoplasma gondii is a widespread protozoan parasite that infects a
      broad range of warm blooded animals as well as humans. The present study was
      investigated to evaluate the effects of allium cepa on renal failur in male rats
      which experimentally infected by Toxoplasma gondii, RH strain. METHODS: Wistar
      male rat (n=40) were allocated into four groups, group one that received
      tachyzoites of T. gondii (ip) (n=10), group two that received tachyzoites of T.
      gondii (ip), plus fresh onion juice by gavages method (n=10), group three
      received just fresh onion juice by gavages method (n=10) and control group (n=10)
      that received nothing. Animals were kept in standard condition. In 30 day after
      inducing Toxoplasma infection, 5cc blood was collected for serum protein and TAC
      levels. Kidney tissues of Rat in whole groups were removed and prepared for
      apopetosis analysis. RESULTS: Serum protein and kidneys weights were
      significantly decreased in groups that were infected with T. gondii, in
      comparison to control and onions groups. Kidneys Apopetosis in toxoplasma group
      significantly increased in comparison to control group (P<0.05).level of TAC was
      significantly increased in groups that received onio juice (P<0.05). CONCLUSION:
      This study showed that T. gondii have significantly effect on serum protein and
      TAC, apopetosis and fresh onion juice returned and treated this harmful effect,
      so it is suggested that eating of onion is useful in toxoplasma infection.

PMID- 24312765
TI  - Evaluation and optimization of chitosan derivatives-based gene delivery system
      via kidney epithelial cells.
AB  - PURPOSE: Non-viral vectors have been widely proposed as safer alternatives to
      viral vectors, and cationic polymers have gained increasing attention because
      they can form self-assembly with DNA. Chitosan is also considered to be a good
      candidate for gene delivery systems, since it is already known as a
      biocompatible, biodegradable, and low toxic material with high cationic
      potential. However, low solubility and transfection efficiency need to be
      overcome prior to clinical trial. In this work, we focus on alkyl modified
      chitosan which might be useful in DNA condensing and efficient gene delivery.
      METHODS: N, N- Diethyl N- Methyl (DEMC) and N- Triethyl Chitosan (TEC) were
      synthesized from chitosan polymer. In order to optimize the polymers for gene
      delivery, we used FITC-dextran (FD). Then the optimized polymer concentrations
      were used for gene delivery. Fluorescent microscope was used, in order to
      evaluate the polymers' efficiency for gene delivery to human embryonic kidney
      epithelial cells (HEK 293T). RESULTS: This modification increased chitosan's
      positive charge, thus these chitosan derivatives spontaneously formed complexes
      with FD, green fluorescence protein plasmid DNA (pEGFP), red fluorescence protein
      plasmid DNA (pJred) and fluorescent labeled miRNA .RESULTS gained from
      fluorescent microscope showed that TEC and DEMC were able to transfer FD, DNA and
      miRNA (micro RNA) to HEK cell line. CONCLUSION: We conclude that these chitosan
      derivatives present suitable characteristics to be used as non-viral gene
      delivery vectors to epithelial cells.

PMID- 24312766
TI  - Anti-bacterial performance of azithromycin nanoparticles as colloidal drug
      delivery system against different gram-negative and gram-positive bacteria.
AB  - PURPOSE: Azithromycin (AZI) is a new macrolide antibiotic with a better activity
      against intracellular gram negative bacteria in comparison with Erythromycin. The
      purpose of this research was to prepare AZI nanoparticles (NPs) using PLGA
      polymer and to compare the effectiveness of prepared nanoparticles with untreated
      AZI solution. METHODS: AZI NPs were prepared by Modified Quasi-Emulsion Solvent
      Diffusion method. The antibacterial activities of prepared NPs in comparison with
      AZI solution were assayed against indicator bacteria of Escherichia coli (PTCC
      1330), Haemophilus influenzae (PTCC 1623) and Streptococcus pneumoniae (PTCC
      1240) using agar well diffusion. Inhibition zone diameters (IZD) of nano
      formulation were compared to the corresponding untreated AZI. Mean Inhibitory
      Concentration (MIC) values of AZI were also determined using serial dilution
      method in nutrient broth medium. RESULTS: Mean IZD of nano-formulations for all
      indicator bacteria were significantly higher than that of untreated AZI (P<0.01).
      The enhanced antibacterial efficacy was more dominant in the gram positive
      species. The MIC values of NPs against the tested bacteria were reduced 8 times
      in comparison to those of untreated AZI. CONCLUSION: These results indicated an
      improved potency of AZI NPs which could be attributed to the modified surface
      characteristics as well as increased drug adsorption and uptake.

PMID- 24312767
TI  - On the mechanism of agglomeration in suspension.
AB  - PURPOSE: Agglomeration in suspension is a size enlargement method that
      facilitates operation of solid processing and preserves the solubilization
      properties of fine particles. A small quantity of binder liquid is added into a
      suspension of microparticles, directly in the stirred vessel where the
      precipitation or crystallization took place. This study deals with the evaluation
      of the effect of agitation time before and after addition of binder liquid on
      agglomerates properties in order to give some insights into the mechanism of the
      formation of the agglomerates. METHODS: Carbamazepine is used as a model drug and
      isopropyl acetate is used as binder liquid. The agglomerates characterization
      includes the particle size, morphology and density. RESULTS: The results showed
      that, by increasing the agitation time before addition of binder liquid, smaller
      agglomerates with less density and irregular forms composed of larger crystals
      were obtained. However, with increasing agitation time after addition of binder
      liquid the agglomerates size and density increases and morphology improves.
      Indeed, by continuing agitation along the course of agglomeration the properties
      of the particles change gradually but substantially. CONCLUSION: With optimized
      agitation time before and after addition of binder liquid, spherical and dense
      agglomerates can be obtained.

PMID- 24312768
TI  - In vitro evaluation of tetrazoles as a novel class of Antimycobacterium
      tuberculosis agents.
AB  - PURPOSE: We report here the antimycobacterial activity of some already
      synthesized tetrazole derivatives containing tetrazole against Mycobacterium
      tuberculosis strain H37Rv. METHODS: In vitro evaluation of the antitubercular
      activity was carried out within the Tuberculosis Antimicrobial Acquisition &
      Coordinating Facility (TAACF) screening program for the discovery of novel drugs
      for the treatment of tuberculosis. Under the direction of the US National
      Institute of Allergy and Infectious Diseases (NIAID), Southern Research Institute
      that coordinates the overall program. The method of TAACF was followed for
      evaluation of activity. RESULTS: This new structural class of compounds showed
      high activity against the bacilli. The activity depends on the substituent's
      present in azatidinone core. Compounds having a 4-MeOC6H4 4-N(CH3)2C6H4 group as
      the substituent on beta-lactam ring were active. The highest activity was
      registered for compounds having 4-MeOC6H4 as substituent. CONCLUSION: The new
      compounds showed high potency and promising antitubercular activity and should be
      regarded as new hits for further development as a novel class of
      Antimycobacterium tuberculosis agents.

PMID- 24312769
TI  - Application of lactobionic acid and nonionic surfactants as solubilizing agents
      for parenteral formulation of clarithromycin.
AB  - PURPOSE: The purpose of this paper is to enhance the solubility of clarithromycin
      (CLR) using nonionic surfactants and some type of acids for preparation of the
      new formulations. METHODS: Myrj 52 and chremophor (2.5 and 5% w/v) were used in
      two concentrations. To investigate solubility, the formulations were shaken for
      48 hours at room temperature. For stability test, lyophilized samples were
      maintained in refrigerator at 4 degrees  C, and in oven at 40 degrees  C. Drug
      analysis was performed by reverse phase high performance liquid chromatography
      (HPLC) with ultraviolet detection. RESULTS: Solubility tests indicated that
      lactobionic acid was the most effective to increase clarithromycin solubility and
      chremophor showed higher enhancing effect than myrj 52 on CLR solubility. The
      stability tests results also confirmed that shelf-lives of all formulations have
      been the equivalent to 24 months. CONCLUSION: On the whole, formulations
      described in this article may be very suitable for industrial-scale manufacturing
      and clinical application.

PMID- 24312770
TI  - Design of vancomycin RS-100 nanoparticles in order to increase the intestinal
      permeability.
AB  - PURPOSE: The purpose of this work was to preparation of vancomycin (VCM)
      biodegradable nanoparticles to improve the intestinal permeability, using water
      in-oil-in-water (W/O/W) multiple emulsion method. METHODS: The vancomycin-loaded
      nanoparticles were created using double-emulsion solvent evaporation method.
      Using Eudragit RS100 as a coating material. The prepared nanoparticles were
      identifyed for their micromeritic and crystallographic properties, drug loading,
      particle size, drug release, Zeta potential, effective permeability (Peff) and
      oral fractional absorption. Intestinal permeability of VCM nanoparticles was
      figured out, in different concentrations using SPIP technique in rats. RESULTS:
      Particle sizes were between 362 and 499 nm for different compositions of VCM-RS
      100 nanoparticles. Entrapment efficiency expansed between 63%-94.76%. The highest
      entrapment efficiency 94.76% was obtained when the ratio of drug to polymer was
      1:3. The in vitro release studies were accomplished in pH 7.4. The results showed
      that physicochemical properties were impressed by drug to polymer ratio. The FT
      IR, XRPD and DSC results ruled out any chemical interaction betweenthe drug and
      RS-100. Effective intestinal permeability values of VCM nanoparticles in
      concentrations of 200, 300 and 400 MUg/ml were higher than that of solutions at
      the same concentrations. Oral fractional absorption was achieved between 0.419
      0.767. CONCLUSION: Our findings suggest that RS-100 nanoparticles could provide a
      delivery system for VCM, with enhanced intestinal permeability.

PMID- 24312771
TI  - Antimicrobial Activity of Chlorhexidine, Peracetic acid/ Peroxide hydrogen and
      Alcohol based compound on Isolated Bacteria in Madani Heart Hospital, Tabriz,
      Azerbaijan, Iran.
AB  - PURPOSE: The aim of present study was to investigate the effect of chemical
      agents on the clinical isolates in Madani Heart Hospital, Tabriz, Iran. METHODS:
      The minimum bactericide concentration (MBC) of disinfectants including
      chlorhexidine (Fort), peracetic acid (Micro) and an alcohol based compound
      (Deconex) on selected bacteria at various dilutions were determined by the
      standard suspension technique. RESULTS: MBC of Micro, Fort and Deconex were 2-128
      mg/L, 2-64 mg/L and 4 - 32 mg/L, respectively. The Gram negative bacteria were
      more resistance to disinfectant relation to Gram positive bacteria. CONCLUSION:
      The results showed that these agents are able to eradicate the bacteria and they
      can be used lonely.

PMID- 24312772
TI  - Socio-demographic characteristics of the addicted inmates of Qom and Tabriz
      prisons in Iran.
AB  - PURPOSE: The aim of this investigation was to study the factors responsible for
      drug addiction amongst the inmates of Tabriz and Qom prisons, to further
      understand the reasons for drug abuse particularly in the young and find improved
      methods for combating these widespread problems. METHODS: A multi-choice
      questionnaire was provided to inmates to potentially assess the reasons for their
      drug addiction psychiatric, personal, social, economical, and political factors
      were thought to be implicated. Two hundred drug addicted prisoners were
      individually interviewed randomly in both Tabriz and Qom prisons. A questionnaire
      including questions about the inmates' demographic characteristics and 49
      multiple answers questions, was provided to identify the effects of different
      reasons for drug addiction for instance: psychiatric, personal, social,
      economical, and political factors. The collected data were analyzed by Student t
      test and chi-squared test using SPSS software. RESULTS: The results showed that
      the following factors could lead to drug addiction e.g. company with addicted
      friends and offenders, curiosity, imitation, illiteracy, family problems, crowded
      family, poverty, unemployment, and lack of self confidence. There were
      significant differences between Tabriz and Qom prisoners in relation to age,
      starting age of addiction, job, income, education, class of addiction, marital
      status, and hobbies. Mean age, mean starting age of addiction, poverty, alcohol
      drinking before addiction, marital status, heroin addiction, codeine and
      benzodiazepines abuse were significantly greater for Tabriz prisoners than those
      of Qom. CONCLUSION: It is clear that the governmental programs for reducing
      unemployment, creation of safe hobbies, proper control on drug dispensing in the
      pharmacies, proper birth control programs, and encouragement to higher education
      could alleviate addiction problem in Iran.

PMID- 24312773
TI  - Evaluation of the effect of CaCl2 and alginate concentrations and hardening time
      on the characteristics of Lactobacillus acidophilus loaded alginate beads using
      response surface analysis.
AB  - PURPOSE: This article describes preparation and characterization of beads of
      alginate containing probiotic bacteria of Lactobacillus acidophilus DMSZ20079.
      METHODS: Fourteen formulations using different alginate (ALG) and CaCl2
      concentrations as well as hardening times were prepared using extrusion
      technique. The prepared beads were characterized in terms of size, morphology,
      encapsulation efficiency and bacterial viabilities in acid (pH 1.8, 2 hours)
      condition. RESULTS: The results showed that spherical beads with narrow size
      distribution ranging from 1.32+/-0.04 to 1.70+/-0.07 mm were achieved with
      encapsulation efficiency higher than 98%. Surface response analysis revealed that
      alginate concentration was the important factor for the size, shape and
      encapsulation efficiency of prepared beads. Furthermore, survived bacteria after
      acid exposure in all prepared beads (63-83%) were significantly higher than those
      of untreated cells (39%) and enhanced by increasing alginate concentration.
      Surface response analysis revealed that the effect of all three factors of
      alginate and CaCl2 concentrations as well as hardening times were significant in
      acid viability, however alginate concentration played the most important role
      according to its regression coefficient. CONCLUSION: Among alginate and CaCl2
      concentrations as well as hardening times, alginate concentration was the most
      variable in the characteristics of Alginate beads.

PMID- 24312774
TI  - Protective effect of NAC against malathion-induced oxidative stress in freshly
      isolated rat hepatocytes.
AB  - PURPOSE: Induction of oxidative stress by Organophosphate compounds (OPs) has
      been previously reported. In the present work, the mechanism of protective
      effects of N-acetylcysteine as a glutathion (GSH) prodrug against malathion
      induced cell toxicity was investigated. In this work, freshly isolated rat
      hepatocytes were used to determine the effect of NAC on malathion-induced
      cytotoxicity, formation of reactive oxygen species (ROS) and mitochondrial
      dysfunction. METHODS: Rat hepatocytes were isolated using collagenase perfusion
      and then cell viability, mitchondrial membrane potential (MMP) and ROS formation
      were determined using trypan blue exclusion, Rhodamine 123 fluorescence and
      fluorogenic probe, 2', 7' -dichlorofluorescin diacetate (DCFH-DA), respectively.
      RESULTS: Despite the protective effect of NAC on malathion-induced cell toxicity
      and MMP dysfunction, its efficacy against ROS formation was not adequate to
      completely protect the cells. CONCLUSION: Cytotoxic effects of malathion
      regardless of its cholinergic feature, is started with gradual free radical
      production but, the main factor that causes cell death, is mitochondrial
      dysfunction, so that reduction of ROS formation alone is not sufficient for cell
      survival, and the maintenance of mitochondrial integrity through different
      mechanisms is the most ameliorative factor specially at high levels of cell
      damage, as NAC seemed to protect cells with various fashions apart from ROS
      scavenging in concentrations higher than malathion's LC50.

PMID- 24312775
TI  - Antioxidant and Antimicrobial activity of Pedicularis sibthorpii Boiss. And
      Pedicularis wilhelmsiana Fisch ex.
AB  - PURPOSE: This research paper presents antioxidant and antimicrobial activities of
      Pedicularis sibthorpii and Pedicularis wilhelmsiana which grow in Azerbaijan/Iran
      with claimed a lot of therapeutic effects. METHODS: DPPH assay and agar well
      diffusion method were carried out to determine antioxidant and antimicrobial
      activities respectively. RESULTS: Methanolic extract showed better antioxidant
      activity compared to other crude extracts (n-hexane and dichloromethane).
      Methanolic extracts of both Pedicularis sibthorpii and Pedicularis wilhelmsiana
      were found to have antibacterial activity especially against gram positive
      strains of S. ureus, S.epidermidis. No antifungal activity was observed in the
      tested extracts. CONCLUSION: Existence of some phenolic compounds in methanolic
      extracts, such as phenylethanoids and flavonoids (found in other species of
      Pedicularis), which cause both antioxidant and antibacterial activities, is
      probable. Antimicrobial and antioxidant activity of the methanolic extracts
      supports further studies related to phytochemical investigation and bioassay of
      different fractions to isolate pure compounds of plants.

PMID- 24312776
TI  - Utilization of thin film method for preparation of celecoxib loaded liposomes.
AB  - PURPOSE: Celecoxib is nonsteroiddal anti-inflammatory drug that has been used
      extensively to treat patients with arthritis. The aim of the present study was to
      formulate and characterize liposomal vesicles loaded with celecoxib. METHODS:
      Liposomes were prepared by thin film method using soya lecithin and cholesterol.
      The release of drug was determined using a dialysis membrane method. Liposomes
      were characterized by Differential Scanning Calorimetery (DSC), Transmission
      Electron Microscopy (TEM) and their particle size was also determined. RESULTS:
      The results showed that the drug encapsulation efficiency was 67.34% and there
      was 67.16% release after 0.5, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h. RESULTS of
      particle size determination showed a mean size of 677nm and nanoparticles were
      spherical as shown by TEM. The DSC curve of lecithin, cholesterol and celecoxib
      were different from celecoxib containing liposome. CONCLUSION: The results of
      characterization of the vesicles indicated the potential application of celecoxib
      loaded liposome as carrier system.

PMID- 24312777
TI  - Antiproliferative effect of gynura procumbens (lour.) Merr. Leaves etanolic
      extract on 7,12-dimethylbenz(a)antracene induced male rat liver.
AB  - PURPOSE: The leaves of Gynura procumbens (Lour.) Merr. has been traditionally
      used as anticancer. Ethanolic extract of G. procumbens leaves (EGP) showed
      cytotoxic activity and anticancer activity in animal cancer model. This study was
      conducted to observe antiproliferative effect using male rat's liver cells
      induced by 7,12-dimethylbenz(a)antracene (DMBA). METHODS: Forty days old Sprague
      Dawley male rats were divided into 4 groups, (1) 0.5 % CMC Na, (2) 20 mg/kg BW
      DMBA p.o ten times in three weeks, (3) DMBA+300 mg/kg BW of EGP, and (4) DMBA+750
      mg/kg BW of EGP. The extract was dissolved into 0.5 % CMC-and administered daily
      per oral one week before, during and terminated 1 week after the DMBA induction.
      After sixthteen week experiment, rat livers were sectioned and stained with
      Haematoxyllene and Eosin (H&E) and AgNOR. RESULTS: Histopatology profile showed
      no primary liver tumor on DMBA group. mAgNOR value of DMBA+300 mg/kg BW EGP
      showed significant antiproliferative effect compared to DMBA group. CONCLUSION:
      Ethanolic extract of G. procumbens leaves showed antiproliferative activity on
      male rats liver induced by DMBA.

PMID- 24312778
TI  - Antioxidant Activity of Rhizoma Cibotii in vitro.
AB  - PURPOSE: The paper tried to systematically investigate the in vitro antioxidant
      activity of Rhizoma Cibotii (RC) for the first time. METHOD: The methanol extract
      from RC (MERC) was prepared then systematically investigated by various
      antioxidant assays, including: DPPH* (1, 1-diphenyl-2-picrylhydrazyl radical),
      ABTS*(+) (3-ethylbenzthiazoline-6- sulfonic acid diammonium salt radical), *O2-
      (superoxide anion radical), *OH (hydroxyl radical) scavenging assays, Fe(3+)
      reducing power, Cu(2+) reducing power assays, compared with positive controls
      Trolox (+/- -6 -hydroxyl -2,5, 7, 8-tetramethlychromane-2-carboxylic acid) and
      BHA (butylated hydroxyanisole). Its total phenolics and caffeic acid content were
      also measured by Folin-Ciocalteu method and HPLC, respectively. RESULT: MERC
      exhibited effective antioxidant activity in dose-dependent manners and its IC50
      values were calculated as 44.2 +/- 0.62, 19.84 +/- 0.31, 137.66 +/- 2.90, 22.94
      +/- 0.90, 289.73 +/- 46.17, 53.52 +/- 1.51 ug /mL,for DPPH*, ABTS*(+), *O2 (-),
      *OH scavenging assays, Fe(3+) reducing power, Cu(2+) reducing power assays,
      respectively. Its total phenolics content was 50.88 +/- 1.24 mg CAE /g and the
      caffeic acid content was 1.82 +/- 0.19 mg/g. CONCLUSION: Rhizoma Cibotii has
      effective in vitro antioxidant activity which may attribute to its total
      phenolics, among which caffeic acid can be considered as one of the active
      components. The pharmacological effects or healthcare functions of whole RC may
      result from the synergistic effects caused by the combination of its components
      and its antioxidant effect plays an important role in the synergistic effects.

PMID- 24312779
TI  - Derivative spectrophotometric method for estimation of antiretroviral drugs in
      fixed dose combinations.
AB  - PURPOSE: Lamivudine is cytosine and zidovudine is cytidine and is used as an
      antiretroviral agents. Both drugs are available in tablet dosage forms with a
      dose of 150 mg for LAM and 300 mg ZID respectively. METHOD: The method employed
      is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm
      were selected for the estimation of the Lamovudine and Zidovudine respectively by
      taking the first order derivative spectra. The conc. of both drugs was determined
      by proposed method. The results of analysis have been validated statistically and
      by recovery studies as per ICH guidelines. RESULT: Both the drugs obey Beer's law
      in the concentration range 10-50 MUg mL-1,for LAM and ZID; with regression 0.9998
      and 0.9999, intercept - 0.0677 and - 0.0043 and slope 0.0457 and 0.0391 for LAM
      and ZID, respectively.The accuracy and reproducibility results are close to 100%
      with 2% RSD. CONCLUSION: A simple, accurate, precise, sensitive and economical
      procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet
      dosage form have been developed.

PMID- 24312780
TI  - Modified synthesis of erlotinib hydrochloride.
AB  - PURPOSE: An improved and economical method has been described for the synthesis
      of erlotinib hydrochloride, as a useful drug in treatment of non-small-cell lung
      cancer. METHOD: Erlotinib hydrochloride was synthesized in seven steps starting
      from 3, 4-dihydroxy benzoic acid. In this study, we were able to modify one of
      the key steps which involved the reduction of the 6-nitrobenzoic acid derivative
      to 6-aminobenzoic acid derivative. An inexpensive reagent such as ammonium
      formate was used as an in situ hydrogen donor in the presence of
      palladium/charcoal (Pd/C) instead of hydrogen gas at high pressure. RESULT: This
      proposed method proceeded with 92% yield at room temperature. Synthesis of
      erlotinib was completed in 7 steps with overall yield of 44%. CONCLUSION: From
      the results obtained it can be concluded that the modified method eliminated the
      potential danger associated with the use of hydrogen gas in the presence of
      flammable catalysts. It should be mentioned that the catalyst was recovered after
      the reaction and could be used again.

PMID- 24312781
TI  - Determination of aflatoxins in nuts of Tabriz confectionaries by ELISA and HPLC
      methods.
AB  - PURPOSE: Aflatoxins (AFs) are a group of mycotoxins and secondary metabolites of
      various species of Aspergillus. There are various forms of aflatoxins including
      B1, B2, G1, G2, M1 and M2 types. Aflatoxins cause important health problems and
      have high potential effect on liver cancer. Therefore, numerous investigations
      have been conducted during last three decades. The aim of this work is to
      determine the contamination levels of nuts used by the confectionaries in Tabriz.
      METHOD: A total of 142 samples including 35 almond , 26 walnut, 4 seeds of
      apricot, 6 sunflower seeds kernel, 6 sesame seed, 6 peanuts , 32 pistachio,13
      hazelnuts and 14 cashews samples were collected from Tabriz confectionaries. The
      ELISA method was employed for the screening of total aflatoxins. RESULT: In 13
      cases (28.1% of pistachios, 5.1% of walnuts and 7.1% of cashews) contamination
      rate of higher than 15 ppb were observed. The HPLC method was applied for the
      confirmation of ELISA results. Aflatoxin B1 was the highest detected AFs.
      CONCLUSION: The overall results of the tested samples indicated that the rate of
      contamination of pistachios is higher than the other tested samples.

PMID- 24312782
TI  - The effect of chronic administration of buspirone on 6-hydroxydopamine-induced
      catalepsy in rats.
AB  - PURPOSE: Several evidences show that serotonergic neurons play a role in the
      regulation of movements executed by the basal ganglia. Recently we have reported
      that single dose of buspirone improved 6-hydroxydopamine (6-OHDA) and haloperidol
      induced catalepsy. This study is aimed to investigate effect of chronic
      intraperitoneal (i.p.) administration of buspirone on 6-OHDA-induced catalepsy in
      male Wistar rats. METHOD: Catalepsy was induced by unilateral infusion of 6-OHDA
      (8 MUg/2 MUl/rat) into the central region of the SNc and was assayed by the bar
      test method 5, 60, 120 and 180 min after drugs administration in 10th day. The
      effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days) was assessed in 6-OHDA
      lesioned rats. RESULT: The results showed that chronic injection of buspirone
      (0.5, 1 and 2 mg/kg, i.p. for 10 days) decreased catalepsy when compared with the
      control group. The best anticataleptic effect was observed at the dose of 1
      mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2
      methoxyphenyl)- 4-[4-(2-phthalimido) butyl]piperazine hydrobromide (NAN-190), 0.5
      mg/kg, i.p.,as a 5-HT1A receptor antagonist. CONCLUSION: Our study indicates that
      chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal
      model of parkinson's disease (PD). We also suggest that buspirone may be used as
      an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order
      to prove this hypothesis, further clinical studies should be done.

PMID- 24312783
TI  - Hypothesis: silver nanoparticles as an adjuvant for cancertherapy.
AB  - Cytotoxic agents are a main part of therapeutic process against the observed
      tumors, which lead to some unwished damages, due to drug uptake by normal body
      cells causing various tissue/organ failures associated with formal administration
      manners. But nowadays the risk is reduced by new target therapy techniques, of
      which the observed physical nature of micelles and nanosilver particles,
      governing their special behavior, could help using micelle-coated silver
      nanoparticles as a novel adjuvant for cancer target therapy. 

PMID- 24312784
TI  - Development and validation of an HPLC method for the analysis of sirolimus in
      drug products.
AB  - PURPOSE: The aim of this study was to develop a simple, rapid and sensitive
      reverse phase high performance liquid chromatography (RP-HPLC) method for
      quantification of sirolimus (SRL) in pharmaceutical dosage forms. METHODS: The
      chromatographic system employs isocratic elution using a Knauer- C18, 5 mm, 4.6 *
      150 mm. Mobile phase consisting of acetonitril and ammonium acetate buffer set at
      flow rate 1.5 ml/min. The analyte was detected and quantified at 278nm using
      ultraviolet detector. The method was validated as per ICH guidelines. RESULTS:
      The standard curve was found to have a linear relationship (r(2) > 0.99) over the
      analytical range of 125-2000ng/ml. For all quality control (QC) standards in
      intraday and interday assay, accuracy and precision range were -0.96 to 6.30 and
      0.86 to 13.74 respectively, demonstrating the precision and accuracy over the
      analytical range. Samples were stable during preparation and analysis procedure.
      CONCLUSION: Therefore the rapid and sensitive developed method can be used for
      the routine analysis of sirolimus such as dissolution and stability assays of pre
      and post-marketed dosage forms.

PMID- 24312785
TI  - Preparation and evaluation of tretinoin microemulsion based on pseudo-ternary
      phase diagram.
AB  - PURPOSE: The aim of the present research was to formulate a transparent
      microemolsion as a topical delivery system for tretinoin for the treatment of
      acne. METHODS: Microemulsion formulations prepared by mixing appropriate amount
      of surfactant including Tween 80 and Labrasol, co-surfactant such as propylene
      glycol (PG) and oil phase including isopropyl myristate - transcutol P (10:1
      ratio). The prepared microemolsions were evaluated regarding their particle size,
      zeta potential, conductivity, stability, viscosity, differential scanning
      calorimetry (DSC), scanning electron microscopy (SEM), refractory index (RI) and
      pH. RESULTS: The results showed that maximum oil was incorporated in
      microemolsion system that was contained surfactant to co-surfactant ratio (Km) of
      4:1. The mean droplets size range of microemulsion formulation were in the range
      of 14.1 to 36.5 nm and its refractory index (RI) and pH were 1.46 and 6.1,
      respectively. Viscosity range was 200-350 cps. Drug release profile showed 49% of
      the drug released in the first 8 hours of experiment belong to ME-7. Also,
      Hexagonal and cubic structures were seen in the SEM photograph of the
      microemulsions. CONCLUSION: physicochemical properties and in vitro release were
      dependent upon the contents of S/C, water and, oil percentage in
      formulations.Also, ME-7 may be preferable for topical tretinoin formulation.

PMID- 24312786
TI  - Fluoxetine improves the effect of levodopa on 6-hydroxy dopamine-induced motor
      impairments in rats.
AB  - PURPOSE: Long term L-DOPA therapy in Parkinson's disease is associated with
      troublesome motor fluctuations such as L -DOPA Induced dyskinesia and wearing off
      effect. Our recent study showed that activation of 5-HT1A receptors could improve
      the anti-cataleptic effect of L-DOPA in parkinsonian rats. In this study we
      investigated the effect of fluoxetine on anti-parkinsonian effect of L-DOPA in 6
      hydroxydopamine (6-OHDA)-lesioned rats. METHODS: Catalepsy and motor
      incoordination were induced by unilateral injection of 6-OHDA (8MUg/2MUl/rat)
      into the central region of the sabstantia nigra pars compacta (SNc). After 3
      weeks as a recovery period, these rats injected intraperitoneally (i.p.) L-DOPA
      (15 mg/kg) twice daily for 20 consecutive days, and anti-parkinsonian effect of L
      DOPA was investigated by bar-test and rotarod on days 5, 10, 15 and 20. RESULTS:
      The results showed that L-DOPA is able to improve motor coordination in rotarod
      only until day 15 and these effects of L-DOPA were abolished on the day 20. On
      day 21, rats were co-injected with fluoxetine (0.1, 0.5 and 1mg/kg, i.p.) and L
      DOPA (15 mg/kg, i.p.). Fluoxetine increased anti-cataleptic effect of L-DOPA at
      the dose of 1 mg/kg, while fluoxetine had not any impact on the effect of L-DOPA
      in rotarod test. The effect of fluoxetine (1 mg/kg, i.p.) on anti-cataleptic
      effect of L-DOPA (15 mg/kg, i.p.) was reversed by 1-(2-methoxyphenyl)-4-(4
      phthalimidobutyl) piperazine hydrobromide (NAN-190; 0.5 mg/kg, i.p.), as a 5-HT1A
      receptor antagonist. CONCLUSION: According to the results, it may be concluded
      that fluoxetine improves 6-OHDA-induced catalepsy and motor imbalance in L-DOPA-
      treated rats through activation of 5-HT1A. Further studies should be designed to
      clarify the precise mechanism of interaction between 5-HT1A and dopaminergic
      neurons.

PMID- 24312787
TI  - Development of a dispersive liquid-liquid microextraction technique for the
      extraction and spectrofluorimetric determination of fluoxetine in pharmaceutical
      formulations and human urine.
AB  - PURPOSE: Fluoxetine is the most prescribed antidepressant drug worldwide. In this
      work, a new dispersive liquid-liquid microextraction (DLLME) method combined with
      spectrofluorimetry has been developed for the extraction and determination of FLX
      in pharmaceutical formulations and human urine. METHODS: For FLX determination,
      the pH of a 10 mL of sample solution containing FLX, was adjusted to 11.0. Then,
      800 uL of ethanol containing 100 uL of chloroform was injected rapidly into the
      sample solution. A cloudy solution was formed and FLX extracted into the fine
      droplets of chloroform. After centrifugation, the extraction solvent was
      sedimented and supernatant aqueous phase was readily decanted. The remained
      organic phase was diluted with ethanol and its fluorescence was measured at 292+/
      3 nm after excitation at 234+/-3 nm. RESULTS: Some important parameters
      influencing microextraction efficiency were investigated. Under the optimum
      extraction conditions, a linear calibration curve in the range of 10 to 800 ng/mL
      with a correlation coefficient of r(2) = 0.9993 was obtained. Limit of detection
      (LOD) and limit of quantification (LOQ) were found to be 2.78 and 9.28 ng/mL,
      respectively. The relative standard deviations (RSDs) were less than 4%. Average
      recoveries for spiked samples were 93-104%. CONCLUSION: The proposed method gives
      a very rapid, simple, sensitive, wide dynamic range and low-cost procedure for
      the determination of FLX.

PMID- 24312788
TI  - Zero flow global ischemia-induced injuries in rat heart are attenuated by natural
      honey.
AB  - PURPOSE: In the present study, effects of preischemic administration of natural
      honey on cardiac arrhythmias and myocardial infarction size during zero flow
      global ischemia were investigated in isolated rat heart. METHODS: The isolated
      hearts were subjected to 30 min zero flow global ischemia followed by 120 min
      reperfusion then perfused by a modified drug free Krebs-Henseleit solution
      throughout the experiment (control) or the solution containing 0.25, 0.5, 1 and
      2% of natural honey for 15 min before induction of global ischemia (treated
      groups), respectively. Cardiac arrhythmias were determined based on the Lambeth
      conventions and the infarct size was measured by computerized planimetry.
      RESULTS: Myocardial infarction size was 55.8+/-7.8% in the control group, while
      preischemic perfusion of honey (0.25, 0.5, 1 and 2%) reduced it to 39.3+/-11,
      30.6+/-5.5 (P<0.01), 17.9+/-5.6 (P<0.001) and 8.7+/-1.1% (P<0.001), respectively.
      A direct linear correlation between honey concentrations and infarction size
      reduction was observed (R(2)=0.9948). In addition, total number of ventricular
      ectopic beats were significantly decreased by all used concentrations of honey
      (P<0.05) during reperfusion time. Honey (0.25, 0.5 and 1 %) also lowered
      incidence of irreversible ventricular fibrillation (P<0.05). Moreover, number and
      duration of ventricular tachycardia were reduced in all honey treated groups.
      CONCLUSION: Preischemic administration of natural honey before zero flow global
      ischemia can protect isolated rat heart against ischemia/reperfusion injuries as
      reduction of infarction size and arrhythmias. Maybe, antioxidant and free radical
      scavenging activities of honey, reduction of necrotized tissue and providing
      energy sources may involve in these cardioprotective effects of honey.

PMID- 24312789
TI  - Degenerative effect of Cisplatin on testicular germinal epithelium.
AB  - PURPOSE: The present study was designed to explore the effect of intraperitoneal
      administration of cisplatin in germinal epithelium of mice. There are few reports
      on the side effect of cisplatin on spermatogenesis when are used as anticancer
      drug. Therefore, in the present study the effect of cisplatin on spermatogenesis
      was evaluated by electron microscopy. METHODS: Twenty balb/c mice aging 6-8 weeks
      was used in this study. The mice were divided into two groups, control and
      cysplatin treated. cysplatin was injected for five days as 2.5 mg /kg. The mice
      were sacrificed after 5 weeks and testicular specimens were removed, fixed in
      boueins, formaldeyd fixative and 2.5% Glutaraldehide then prepared for light and
      electron microscopic study. RESULTS: Observation with optic microscope in treated
      group thickness of germinal epithelium was reduced a lot and increased the number
      of apoptotic cells. In some seminiferous tubules only sertoli cells were observed
      and nucleus of spermatogony cells was hetrochromatin. The electron microscopic
      observations showed some irregularity waviness and thickening in basal layer.
      Also myoid cells of this group were thick and contracted. In this group many
      apoptotic cells and damaged organelles were seen. CONCLUSION: It was indicated
      that cisplatin affected testicular germinal epithelium by both cytotoxic effect
      and induction of apoptosis.

PMID- 24312790
TI  - Protective Effect of Prosopis cineraria Against N-Nitrosodiethylamine Induced
      Liver Tumor by Modulating Membrane Bound Enzymes and Glycoproteins.
AB  - PURPOSE: The objective of the present study was to evaluate the protective effect
      of methanol extract of Prosopis cineraria (MPC) against N-nitrosodiethylamine
      (DEN, 200mg/kg) induced Phenobarbital promoted experimental liver tumors in male
      Wistar rats. METHODS: The rats were divided into four groups, each group
      consisting of six animals. Group 1 served as control animals. Liver tumor was
      induced in group 2, 3, and 4 and Group 3 animals received MPC 200mg/kg and Group
      4 animals received MPC 400mg/kg. RESULTS: Administration of DEN has brought down
      the levels of membrane bound enzymes like Na(+)/ K(+) ATPase, Mg(2+) ATPase and
      Ca(2+)ATPase which were later found to be increased by the administration of
      Prosopis cineraria (200 and 400mg/kg) in dose dependent manner. The MPC extract
      also suppressed the levels of glycoproteins like Hexose, Hexosamine and Sialic
      acid when compared to liver tumor bearing animals. CONCLUSION: Our study suggests
      that MPC may extend its protective role by modulating the levels of membrane
      bound enzymes and suppressing glycoprotein levels.

PMID- 24312791
TI  - Lactose engineering for better performance in dry powder inhalers.
AB  - Dry powder inhaler (DPI) is generally formulated as a powder mixture of coarse
      carrier particles and micronized drug with aerodynamic diameters of 1-5 MUm.
      Carrier particles are used to improve drug particle flowability, thus improving
      dosing accuracy, minimizing the dose variability compared with drug alone and
      making them easier to handle during manufacturing operations. Lactose is the most
      common and frequently used carrier in DPIs formulations and nowadays various
      inhalation grades of lactose with different physico-chemical properties are
      available on the market. Therefore, the purpose of this manuscript is to review
      evolution of lactose as a carrier in inhalable formulations, their production and
      the impact of its physico-chemical properties on drug dispersion. This review
      offers a perspective on the current reported studies to modify lactose for better
      performance in DPIs. 

PMID- 24312792
TI  - Resistance to reperfusion injury following short term postischemic administration
      of natural honey in globally ischemic isolated rat heart.
AB  - PURPOSE: RESULTS of our previous study revealed that preischemic perfusion of
      honey before zero flow global ischemia had cardioprotective effects in rat. The
      present study investigated potential resistance to reperfusion injury following
      short term postischemic administration of natural honey in globally ischemic
      isolated rat heart. METHODS: Male Wistar rats were divided into five groups (n=10
      13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to
      equilibrate for 30 min then subjected to 30 min global ischemia. In the control
      group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H)
      solution before ischemia and during 120 min reperfusion. In the treatment groups,
      reperfusion was initiated with K/H solution containing different concentration of
      honey (0.25, 0.5, 1 and 2%) for 15 min and was resumed until the end of 120 min
      with normal K/H solution. RESULTS: In the control group, VEBs number was 784+/
      199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83+/-23
      (P<0.001), 138+/-48 (P<0.01), 142+/-37 (P<0.001) and 157+/-40 (P<0.01),
      respectively. Number and duration of VT and time spent in reversible VF were also
      reduced by honey. In the control group, the infarct size was 54.1+/-7.8%,
      however; honey (0.25, 0.5, 1 and 2%) markedly lowered the value to 12.4+/-2.4,
      12.7+/-3.3, 11.3+/-2.6 and 7.9+/-1.7 (P<0.001), respectively. CONCLUSION:
      Postischemic administration of natural honey in global ischemia showed protective
      effects against ischemia/reperfusion (I/R) injuries in isolated rat heart.
      Antioxidant and radical scavenging activity, lipoperoxidation inhibition,
      reduction of necrotized tissue, presence of rich energy sources, various type of
      vitamins, minerals and enzymes and formation of NO-contain metabolites may
      probably involve in those cardioprotective effects.

PMID- 24312793
TI  - Protective effect of ginger on gentamicin-induced apoptosis in testis of rats.
AB  - PURPOSE: Ginger, the rhizome of Zingiber officinale, is one of the most widely
      used spices for various foods and as an herbal medicine in Asian countries. It
      has been shown that ginger has antioxidant power. Gentamicin is an aminoglycoside
      antibiotic with a very broad spectrum against microbial pathogens, especially the
      gram-negative. Many studies revealed that gentamicin induces an oxidative stress
      status in the testis by increasing free radical formation and lipid peroxidation.
      The present study was designed to investigate on the effects of Ginger as a
      natural anioxidant on testis apoptosis after treatment with gentamicin in rats.
      METHODS: In order to study the recovery effects of ginger on testis apoptosis
      after treatment with gentamicin 40 adult Wistar male rats were selected and
      randomly divided into four groups. Normal salin control (group I) (n=10),
      gentamicin control (group II), ginger control (group III) and gentamicin + ginger
      (group IV) each 10 rats. There was observation of negative effect of Gentamicin
      on testis histology in rats. RESULTS: The results revealed that there was a
      significant increase in apoptosis in group III when compared with other groups
      (P<0.05).However, ginger could decrease apoptosis in group IV that received
      100mg/kg/rat of Ginger. CONCLUSION: Regarding the results, it is recommended that
      administration of ginger with gentamicin might be beneficial in men who receive
      gentamicin to treat infections.

PMID- 24312794
TI  - A comparison of verapamil and digoxin for heart rate control in atrial
      fibrillation.
AB  - PURPOSE: Atrial fibrillation (AF) is one of the most common types of sustained
      dysrhythmia and there are some disagreements about its treatment. The goals of AF
      treatment include the control of ventricular rate, the establishment of sinus
      rhythm and the prevention of thromboembolic events. In this study, the effect of
      verapamil was compared to digoxin on heart rate control in patients with AF.
      METHODS: This descriptive study was conducted in an emergency department (ED) in
      Iran. Sixty patients with a new onset AF and rapid ventricular response receiving
      digoxin or verapamil were included and observed. RESULTS: Two thirty-patient
      groups receiving verapamil or digoxin were evaluated. The heart rate was
      significantly decreased in both groups (p = 0.002); however, the cardioversion
      was not noticed in both of them. The best rate control in verapamil and digoxin
      groups was observed after 5.9 mg (46.7%) and 0.6 mg (36.7%), respectively.
      CONCLUSION: Administration of verapamil in comparison with digoxin has no
      difference to control the heart rate in AF patients. It should be taken into
      consideration that prospective randomized studies should be conducted to identify
      the efficacy and select the best of these two drugs to treat AF patients.

PMID- 24312795
TI  - Antimicrobial and cytotoxic activity of three bitter plants enhydra fluctuans,
      andrographis peniculata and clerodendrum viscosum.
AB  - PURPOSE: In this study, three important medicinal plants (Enhydra fluctuans Lour,
      Clerodendrum viscosum Vent and Andrographis peniculata Wall) of Bangladesh were
      investigated to analyze their antimicrobial and cytotoxic activities against some
      pathogenic microorganisms and Artemia salina (brine shrimp nauplii). METHODS: The
      coarse powder material of leaves of each plant was extracted separately with
      methanol and acetone to yield methanol extracts of leaves of Enhydra fluctuans
      (MLE), Clerodendrum viscosum (MLC) and Andrographis peniculata (MLA), and acetone
      extracts of leaves of Enhydra fluctuans (ALE), Clerodendrum viscosum (ALC) and
      Andrographis peniculata (ALA). The disc diffusion method and the method described
      by Meyer were used to determine the antimicrobial and cytotoxic activities of
      each plant extract. RESULTS: Among the test samples, MLE and ALE showed
      comparatively better antimicrobial activity against a number of bacteria and
      fungi with inhibition zones in the range of 06-15 mm and according to the
      intensity of activity, the efficacy against microorganisms were found in the
      order of Enhydra fluctuans > Andrographis peniculata > Clerodendrum viscosum. In
      cytotoxicity assay, all samples were found to be active against brine shrimp
      nauplii (Artemia salina) and ALA produced lowest LC50 value (7.03 MUg/ml).
      CONCLUSION: Enhydra fluctuans and Andrographis peniculata possesses significant
      antimicrobial and cytotoxic activities.

PMID- 24312796
TI  - Synthesis and pharmacological evaluation of some new pyrimidine derivatives
      containing 1,2,4-triazole.
AB  - PURPOSE: An efficient method has been described for synthesis of 6-(substituted
      aryl)-4-(3,5-diphenyl-1H-1,2,4-triazol-1-yl)-1, 6-dihydropyrimidine-2-thiol, as a
      beneficial antimicrobial, anticonvulsant and anticancer agents. METHODS: The
      clalcones of title compounds were synthesized in three steps and subsequently
      these chalcones were further reacted with thiourea in the presence of KOH in
      ethanol, which led to the formation of dihydropyrimidine derivatives (4a-j).
      Compounds 4a-j were screened for their in vitro antimicrobial activity by agar
      well method and their anticonvulsant activity by the MES model. Anticancer
      activity of two newly synthesized heterocycles were evaluated at National Cancer
      Institute (NCI) Maryland, USA against 60 cell lines of different human tumor at a
      single dose of 10(-5) M. RESULTS: Compound 4b, 4c, 4d, 4i and 4j were exhibited
      significant antimicrobial potential against tested strains at 50MUg/ml and
      100MUg/ml concentrations. Out of the ten compounds studied 4a, 4b, 4c, 4h and 4j
      showed comparable MES activity to Phenytoin and Carbamazepine after 0.5h. Tested
      compounds did not showed to be more potent than standard drugs after 4h. Compound
      4a and 4d were found active on Non-Small Cell Lung Cancer (HOP-92). CONCLUSION:
      Ten noveldihydropyrimidine analogues has been synthesized, characterized and
      found to bepromising antibacterial, anticonvulsant and antitumor agents.

PMID- 24312797
TI  - Dichloromethane and Methanol Extracts of Scrophularia oxysepala Induces Apoptosis
      in MCF-7 Human Breast Cancer Cells.
AB  - PURPOSE: Breast cancer is the most common cause of cancer-related death in women
      worldwide. Therefore, there is an urgent need to identify and develop therapeutic
      strategies against this deadly disease. This study is the first to investigate
      the cytotoxic effects and the mechanism of cell death of Scrophularia oxysepala
      extracts in MCF-7 human breast cancer cells. METHODS: Three extracts of
      Scrophularia oxysepala including the n-hexane, dichloromethane and methanol
      extracts were examined. MTT (3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) and Trypan-blue assays were performed in MCF-7 cells as well as Human
      umbilical vein endothelial cells (HUVEC) to analyze the cytotoxic activity of the
      extracts of Scrophularia oxysepala. Further, the apoptosis inducing action of the
      extracts was determined by TUNEL (terminal deoxy transferase (TdT)-mediated dUTP
      nick- end labeling) test and cell death assay. RESULTS: The results showed that
      the n-hexane extract had no cytotoxic effects but dichloromethane and methanol
      extracts significantly inhibited cell growth and viability in a dose and time
      dependent manner without inducing damage to non-cancerous cell line HUVEC. In
      addition, Cell death assay and DNA fragmentation analysis using TUNEL indicated
      induction of apoptosis by dichloromethane and methanol extracts of Scrophularia
      oxysepala in MCF-7 cells. CONCLUSION: Our studies suggest that this plant may
      contain potential bioactive compound(s) for the treatment of breast cancer.

PMID- 24312798
TI  - Association between Thrombophilia and Repeated Assisted Reproductive Technology
      Failures.
AB  - PURPOSE: This study was performed to investigate the incidence of thrombophilic
      gene mutations in repeated assisted reproductive technology (ART) failures.
      METHODS: The prevalence of mutated genes in the patients with a history of three
      or more previous ART failures was compared with the patients with a history of
      successful pregnancy following ARTs. The study group included 70 patients, 34
      with three or more previously failed ARTs (A) and control group consisted of 36
      patients with successful pregnancy following ARTs (B). All patients were tested
      for the presence of mutated thrombophilic genes including factor V Leiden (FVL),
      Methylenetetrahydrofolate reductase (MTHFR) and Prothrombin (G20210A) using real
      time polymerase chain reaction (RT- PCR). RESULTS: Mutation of FVL gene was
      detected in 5.9% women of group A (2 of 34) compared with 2.8% women (1 of 36) of
      control group (P = 0.6). Mutation of MTHFR gene was found in 35.3% (12 cases) as
      compared with 50% (18 cases) of control (35.3% versus 50%; P = 0.23). Regarding
      Prothrombin, only control group had 5.6% mutation (P = 0.49). No significant
      differences were detected in the incidences of FVL, Prothrombin and MTHFR in the
      study group A compared with the control group B. CONCLUSION: The obtained results
      suggest that thrombophilia does not have a significant effect in ART failures.

PMID- 24312799
TI  - Iontophoretic permeation of lisinopril at different current densities and drug
      concentrations.
AB  - PURPOSE: The purpose of the present work was to assess iontophoretic permeation
      of Lisinopril at different current densities and concentrations for development
      of patient-controlled active transdermal system. METHODS: In vitro iontophoretic
      transdermal delivery of Lisinopril across the pigskin was investigated at three
      different drug concentrations and three different current densities (0.25- 0.75
      mA/cm2) in the donor cell of the diffusion apparatus, using cathodal
      iontophoresis along with the passive controls. RESULTS: For passive permeation,
      the steady state flux significantly increased with the increasing of donor drug
      concentration. At all concentration levels, iontophoresis considerably increased
      the permeation rate compared to passive controls. Iontophoretic transport of
      Lisinopril was to be found increase with current densities. Flux enhancement was
      highest at the lowest drug load and lowest at the highest drug load. CONCLUSION:
      The obtained results indicate that permeation rate of Lisinopril across the
      pigskin can be considerably enhanced, controlled or optimized by the use of
      Iontophoresis technique.

PMID- 24312800
TI  - Determination of the mutagenicity potential of supermint herbal medicine by
      single cell gel electrophoresis in rat hepatocytes.
AB  - PURPOSE: The increasing use of herbal drugs and their easy availability have
      necessitated the use of mutagenicity test to analyze their toxicity and safety.
      The aim of this study was to evaluate the genotoxicity of Supermint herbal
      medicine in DNA breakage of rat hepatocytes in comparison with sodium dichromate
      by single cell gel electrophoresis technique or comet assay. METHODS: Hepatocytes
      were prepared from male wistar rats and were counted and kept in a bioreactor for
      30 minutes. Then cells were exposed to the Supermint herbal medicine at doses of
      125, 250 and 500 ul/ml. Buffer 4 (incubation buffer) and sodium dichromate were
      used as negative and positive control for one hour respectively. Then cell
      suspension with low melting point agarose were put on precoated slides and
      covered with agarose gel. Then lysing, electrophoresis, neutralization and
      staining were carried out. Finally the slides were analyzed with fluorescence
      microscope. The parameter under this analysis was the type of migration which was
      determined according to Kobayashi pattern. RESULTS: With increased dose of
      Supermint herbal medicine the DNA damage was slightly increased (P<0001).
      Conlusion: In overall compared to the positive control significant differences is
      observed which convinced that the crude extract of Supermint in vitro did not
      have mutagenic effect. Conlusion: In overall compared to the positive control
      significant differences is observed which convinced that the crude extract of
      Supermint in vitro did not have mutagenic effect.

PMID- 24312801
TI  - Esmolol: a unique Beta-blocker in maintaining cardiovascular stability following
      neurosurgical procedures.
AB  - PURPOSE: Patients with increased intracranial pressure (ICP) are prone to severe
      cardiac and or cerebral complications following emergence from general anesthesia
      and especially post-extubation phase. Administering beta blockers including
      esmolol is believed to be helpful in providing a stable hemodynamic at the end of
      the surgery and recovery stages and reducing recovery phase length. METHOD: In a
      double-blind prospective randomized clinical trial, 60 adult patients with ASA
      (American Society of Anesthesiologist) class of I-II scheduled to undergo
      elective neurosurgery operations were randomly divided into two groups receiving
      esmolol (n=30) and placebo (n=30) as IV infusion within four minutes prior to
      extubation continued by an IV infusion for 10 minutes after extubation. RESULT:
      There was a significant difference between two groups regarding the changes of
      systolic blood pressure and heart rate at all studied stages after extubation
      (P<=0.05). However, no significant difference existed between esmolol and control
      groups regarding recovery and extubation times emphasizing the fact that esmolol
      is of excellent early recovery and extubation profiles. CONCLUSION: Esmolol is
      advised to be used in preventing hyperdynamic status throughout extubation phase
      without extending recovery phase length.

PMID- 24312802
TI  - How spherical crystallization improves direct tableting properties: a review.
AB  - Direct tableting has been renewed as a preferable process by simply mixing and
      compressing powder to save time and cost in comparison with granule tableting.
      Direct compression tableting as a technique has been successfully applied to
      numerous drugs on the industrial scale, although the success of any procedure,
      and resulting mechanical properties of tablets, is strongly affected by the
      quality of the crystals used. Good flowability, packability and compactability
      are prerequisite for drug to be prepared by direct tableting. When the mechanical
      properties of the drug particles are inadequate a primary granulation is
      necessary. The use of spherical crystallization as a technique appears to be an
      efficient alternative for obtaining suitable particles for direct tableting.
      Spherical crystallization is a particle design technique, by which
      crystallization and agglomeration can be carried out simultaneously in one step
      and which has been successfully utilized for improvement the micromeritic
      properties of crystalline drugs. In this review, we will discuss how the
      micromeritic properties of the particles such as flowability, packability and
      compactability can be improved by spherical crystallization technique. 

PMID- 24312803
TI  - Phytochemical Screening and Antimicrobial Properties of a Common Brand of Black
      Tea (Camellia sinensis) Marketed in Nigerian Environment.
AB  - PURPOSE: This study is aimed at determining chemical constituents and
      antimicrobial activities of a common brand of black tea (Lipton(r)) in Nigeria.
      METHOD: Standard methods were employed for testing carbohydrates, tannins,
      saponins, flavonoids, alkaloids, steroids and terpenes in the tea. Antimicrobial
      activities of methanolic and aqueous extracts of the tea on four standard strains
      of organisms: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and
      Bacillus subtilis were also determined by standard methods. RESULT: RESULTs
      showed that the tea contains tannin and reducing sugar. Concentrations of 1%, 2%,
      4%, 6%, 8% and 10% aqueous and methanolic extract of black tea were prepared and
      their zones of inhibition determined against the four test organisms using the
      cup plate method. This was compared with zones for standard disc Gentamicin (10
      ug) and Erythromycin (15 ug). Pseudomonas aeruginosa was sensitive to 2% to 10%
      aqueous extracts and intermediate to 6%, 8% and 10% methanolic extracts. E. coli
      was intermediately sensitive to 6%, 8% and 10% aqueous extract and 2% to 10%
      methanolic extracts. B. subtilis was intermediately sensitive to 4%, 6% and 8%
      aqueous extract and 4% to 10% methanolic extract but sensitive to 10% aqueous
      extract. Staph.aureus was intermediately sensitive to 4% to 10% aqueous extracts
      and 2% to 10% methanolic extracts. B. subtilis had the lowest MIC values of both
      aqueous and methanolic extracts. In conclusion, this study has shown that
      Lipton(r) has antimicrobial properties on E.coli, Staph.aureus, B.subtilis and
      Ps.aeruginosa and contains tannin and reducing sugar.

PMID- 24312804
TI  - Principles of micellar electrokinetic capillary chromatography applied in
      pharmaceutical analysis.
AB  - Since its introduction capillary electrophoresis has shown great potential in
      areas where electrophoretic techniques have rarely been used before, including
      here the analysis of pharmaceutical substances. The large majority of
      pharmaceutical substances are neutral from electrophoretic point of view,
      consequently separations by the classic capillary zone electrophoresis; where
      separation is based on the differences between the own electrophoretic mobilities
      of the analytes; are hard to achieve. Micellar electrokinetic capillary
      chromatography, a hybrid method that combines chromatographic and electrophoretic
      separation principles, extends the applicability of capillary electrophoretic
      methods to neutral analytes. In micellar electrokinetic capillary chromatography,
      surfactants are added to the buffer solution in concentration above their
      critical micellar concentrations, consequently micelles are formed; micelles that
      undergo electrophoretic migration like any other charged particle. The separation
      is based on the differential partitioning of an analyte between the two-phase
      system: the mobile aqueous phase and micellar pseudostationary phase. The present
      paper aims to summarize the basic aspects regarding separation principles and
      practical applications of micellar electrokinetic capillary chromatography, with
      particular attention to those relevant in pharmaceutical analysis. 

PMID- 24312805
TI  - New approaches in immunotherapy of behcet disease.
AB  - Behcet Disease (BD) is an autoimmune disorder with recurrent ocular, vascular,
      central nervous system, articular, mucocutaneous, and gastrointestinal
      manifestations with unclear etiology and pathogenesis. The further
      characterization of inflammatory features of Behcet's disease may eventually lead
      to development of better treatment options. Clinical and laboratory observations
      suggested an important role of IL-17, IL-21 and neutrophil-mediated process in
      the pathogenesis of BD. New therapeutic modalities target specific and
      nonspecific suppression of the immune system. The various non-specific
      immunosuppressive drugs, used either alone or in combinations, frequently fail to
      control inflammation or maintain remissions. Due to encouraging clinical results
      (i.e. Antigenic specification, prolonged survival with acceptable levels of
      toxicity); antibody-based drugs could be effective for the clinical management of
      Behcet's disease. 

PMID- 24312806
TI  - Analgesic activity of some 1,2,4-triazole heterocycles clubbed with pyrazole,
      tetrazole, isoxazole and pyrimidine.
AB  - PURPOSE: In the present study in vivo analgesic activity of some previously
      synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole
      and pyrimidine ring have been evaluated. METHODS: Acetic acid induced writhing
      method and Hot plate method has been described to study analgesic activity of
      some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and
      pyrimidine as a pharmacological active lead. RESULTS: Thirty six different
      derivatives containing 1,2,4-triazole ring were subjected to study their in vivo
      analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted
      derivatives showed excellent analgesic activity and dimethylamino, furan and
      phenyl substituted derivatives showed moderate analgesic activity in both of the
      methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj
      IV3a and IIj were found to be superior analgesic agents after screening by Acetic
      acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb,
      IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after
      screening of Hot plate method. CONCLUSION: All tested compounds containing 1,2,4
      triazole were found to be promising analgesic agents, for this activity pyrazole,
      tetrazole, isoxazole and pyrimidine leads might be supported.

PMID- 24312807
TI  - Affinity Purification of Tumor Necrosis Factor-alpha Expressed in Raji Cells by
      Produced scFv Antibody Coupled CNBr-Activated Sepharose.
AB  - PURPOSE: Recombinant tumor necrosis factor-alpha (TNF-alpha) has been utilized as
      an antineoplastic agent for the treatment of patients with melanoma and sarcoma.
      It targets tumor cell antigens by impressing tumor-associated vessels. Protein
      purification with affinity chromatography has been widely used in the downstream
      processing of pharmaceutical-grade proteins. METHODS: In this study, we examined
      the potential of our produced anti-TNF-alpha scFv fragments for purification of
      TNF-alpha produced by Raji cells. The Raji cells were induced by
      lipopolysaccharides (LPS) to express TNF-alpha. Western blotting and Fluorescence
      activated cell sorting (FACS) flow cytometry analyses were used to evaluate the
      TNF-alpha expression. The anti-TNF-alpha scFv selected from antibody phage
      display library was coupled to CNBr-activated sepharose 4B beads used for
      affinity purification of expressed TNF-alpha and the purity of the protein was
      assessed by SDS-PAGE. RESULTS: Western blot and FACS flow cytometry analyses
      showed the successful expression of TNF-alpha with Raji cells. SDS-PAGE analysis
      showed the performance of scFv for purification of TNF-alpha protein with purity
      over 95%. CONCLUSION: These findings confirm not only the potential of the
      produced scFv antibody fragments but also this highly pure recombinant TNF-alpha
      protein can be applied for various in vitro and in vivo applications.

PMID- 24312808
TI  - The effects of lyophilization on the physico-chemical stability of sirolimus
      liposomes.
AB  - PURPOSE: The major limitation in the widespread use of liposome drug delivery
      system is its instability. Lyophilization is a promising approach to ensure the
      long-term stability of liposomes. The aim of this study was to prepare sirolimus
      loaded liposomes, study their stability and investigate the effect of
      lyophilization either in the presence or in the absence of lyoprotectant on
      liposome properties. METHODS: Two types of multi-lamellar liposomes, conventional
      and fusogenic, containing sirolimus were prepared by modified thin film hydration
      method with different ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol
      and dioleoylphosphoethanolamine (DOPE), and were lyophilized with or without
      dextrose as lyoprotectant. Chemical stability investigation was performed at 4
      degrees C and 25 degrees C until 6 months using a validated HPLC method. Physical
      stability was studied with determination of particle size (PS) and encapsulation
      efficiency (EE %) of formulations through 6 months. RESULTS: Chemical stability
      test at 4 degrees C and 25 degrees C until 6 months showed that drug content of
      liposomes decreased 8.4% and 20.2% respectively. Initial mean EE % and PS were
      72.8 % and 582 nm respectively. After 6 months mean EE % for suspended form,
      lyophilized without lyoprotectant and lyophilized with lyoprotectant were 54.8 %,
      62.3% and 67.1 % at 4 degrees C and 48.2%, 60.4 % and 66.8 % at 25 degrees C
      respectively. Corresponding data for mean PS were 8229 nm, 2397 nm and 688nm at 4
      degrees C and 9362 nm, 1944 nm and 737 nm at 25 degrees C respectively.
      CONCLUSION: It is concluded that lyophilization with and without dextrose could
      increase shelf life of liposome and dextrose has lyoprotectant effect that
      stabilized liposomes in the lyophilization process.

PMID- 24312809
TI  - Supplementary health benefits of linoleic Acid by improvement of vaginal
      cornification of ovariectomized rats.
AB  - PURPOSE: This study aimed to evaluate the possible estrogenic activity of some
      ingredients of Nigella sativa including Linoleic acid and Gama-Linolenic acid by
      vaginal cornification assay. METHODS: Forty ovariectomized (OVX) rats, aged 16
      weeks were allotted randomly to five groups: negative control (taking 1 ml olive
      oil/ day); positive control (taking 0.2 mg/kg/day Conjucated Equine Estrogen
      CEE); experimental groups (taking 50 mg/kg/day Linoleic acid or 10 mg/kg/day
      Gamma Linolenic acid or 15mg/kg/day Thymoquinone ). All of supplements
      administered via intragastric gavage for 21 consecutive days. To assess estrogen
      like activity, vaginal smear was examined daily and serum estradiol was measured
      at baseline, after 10 days and at the end of experiment. RESULTS: The significant
      occurrence of vaginal cornification cell (p<0.05) after Linoleic acid
      supplementation indicated estrogenic activity of Linoleic acid which was in
      consistency with serum estradiol level, but this effect was not as much as CEE.
      Gama-Linolenic acid also exist a few cornified cell in smear which was not
      significantly differ from those control group. CONCLUSION: Linoleic acid showed
      the beneficial effects on OVX rats' reproductive performance, thereby indicating
      its beneficial role in the treatment of the postmenopausal symptoms.

PMID- 24312810
TI  - Analysis of piroxicam in pharmaceutical formulation and human urine by dispersive
      liquid-liquid microextraction combined with spectrophotometry.
AB  - PURPOSE: Piroxicam, is non-steroidal anti-inflammatory and analgesic agent, which
      is widely used in the treatment of patients with rheumatologic disorders. A new
      analytical approach based on the dispersive liquid-liquid microextraction (DLLME)
      has been developed for the extraction and determination of PX in pharmaceutical
      preparation and human urine. METHODS: From the PX standard solution or solutions
      prepared from real samples, aliquot volumes were pipetted into centrifuge tubes
      and mixed with acetate buffer at pH 3.0 and NaCl solution. The contents were
      subjected to the DLLME, so 700 uL of methanol containing 70 uL of chloroform was
      injected rapidly into a sample solution. A cloudy solution was rapidly produced
      and the PX extracted into dispersed fine droplets. The mixture was centrifuged,
      thus these fine droplets of chloroform were settled. The supernatant aqueous
      phase was readily decanted, then the remained organic phase was diluted with
      ethanol and the absorbance measured at 355 +/- 3 nm against a reagent blank.
      RESULTS: The main factors affecting the extraction efficiency such as pH,
      extraction and disperser solvent types and etc. were studied and optimized
      systematically. Under optimized conditions, the calibration graphs were linear
      over the range of 0.2 to 4.8 ug/mL. The limit of detection and relative standard
      deviation were found to be 0.058 ug/mL and 2.83%, respectively. Relative
      recoveries in the spiked samples ranged from 97 to 110%. CONCLUSION: Using the
      developed method PX can be analyzed in pharmaceutical formulation and human urine
      sample in a simpler, cheaper and more rapid manner.

PMID- 24312811
TI  - Attitudinal Changes Using Peer Education Training in the Prevention of HIV/AIDS:
      A Case Study of Youths in North Central Nigeria.
AB  - PURPOSE: HIV/AIDS is a major public health issue. Studies have shown that young
      people between the ages of 15 to 24 years accounts for more than 40% of new HIV
      infections. However, new infections could be prevented if the desired impact is
      made on young people through interventions such as effective peer education
      program to improve their knowledge, attitude and practice. Therefore, this study
      is aimed at assessing the impact of peer education vis-a-vis attitudinal changes
      and practices on issues relating to HIV/AIDS among youths in North central
      Nigeria. METHODS: This classical experimental study was carried out in three
      stages, that is: pre-intervention, intervention and post-intervention stages
      among students of Government High School, Ilorin between the ages of 15 and 24
      years. The sample size was 80 students each for study and control groups.
      Proportional gender distribution was ensured in the selection and the sampling
      technique was multistage sampling technique. Data collection was through semi
      structured self administered pre and post evaluation questionnaire. Peer
      education training and forth night mentoring sessions was conducted for the study
      group. Impact of the intervention was assessed after eight weeks. RESULTS:
      Analysis of the result shows that out of the sixteen questions asked on
      respondents' attitude, only four showed statistical significance between the
      study and control group before the intervention which shot up to eleven after
      intervention. Also, the frequency of those having bad practices regarding
      prevention of HIV/AIDS also reduced after intervention. This reduction was much
      more in many instances when compared to the control group. CONCLUSION: This study
      has revealed that peer education training among youth can go a long way in
      educating them on issues relating to HIV/AIDS prevention. It can also bring about
      attitudinal changes and better practices that may help in reducing incidence and
      prevalence of HIV/AIDS in our society.

PMID- 24312812
TI  - Inhibitory and cytotoxic activities of salvia officinalis L. Extract on human
      lymphoma and leukemia cells by induction of apoptosis.
AB  - PURPOSE: Salvia officinalis L., also known as Maryam Goli, is one of the native
      plants used to Persian medicinal herbs. Hence, the objective of this study was to
      examine the in vitro cytotoxic activities of a standardized crude methanol
      extracts prepared from Salvia officinalis L., on a non-Hodgkin's B-cell lymphoma
      (Raji) and human leukemic monocyte lymphoma (U937), Human acute myelocytic
      leukemia (KG-1A) and Human Umbilical Vein Endothelial (HUVEC) cell lines.
      METHODS: The effect of methanolic extract on the inhibition of cell proliferation
      and cytotoxic activity was evaluated by Dye exclusion and Micro culture
      tetrazolium test (MTT) cytotoxicity assay. Cell death ELISA was employed to
      quantify the nucleosome production result from nuclear DNA fragmentation during
      apoptosis and determined whether the mechanism involves induction of apoptosis or
      necrosis. RESULTS: The present results demonstrated that methanolic extract at 50
      to 800 MUg/ml dose and time-dependently suppressed the proliferation of KG-1A,
      U937 and Raji cells by more than 80% (p<0.01), with ascending order of IC50
      values in 24: KG-1A (214.377 MUg/ml), U937 (229.312 MUg/ml) and Raji (239.692
      MUg/ml) when compared with a chemotherapeutic anticancer drug, paclitaxel
      (Toxol), confirming the tumour-selective cytotoxicity. The crude extract however
      did not exert any significant cytotoxic effect on normal cell line HUVEC
      (IC50>800 Ag/ml). Nucleosome productions in KG-1A, Raji and U937 cells were
      significantly increased respectively upon the treatment of Salvia officinalis L.
      extract. CONCLUSION: The Salvia officinalis L. extract was found dose and time
      dependently inhibits the proliferation of lymphoma and leukemic cells possibly
      via an apoptosis-dependent pathway.

PMID- 24312814
TI  - Design and characterization of microemulsion systems for naproxen.
AB  - PURPOSE: This research was aimed to formulate and characterize a microemolsion
      systems as a topical delivery system of naproxen for relief of symptoms of
      rheumatoid arthritis, osteoarthritis and treatment of dysmenorrheal. METHODS: ME
      formulations prepared by mixing of appropriate amount of surfactant including
      Tween 80 and Span 80, co-surfactant such as propylene glycol (PG) and oil phase
      including Labrafac PG - transcutol P (10:1 ratio). The prepared microemolsions
      were evaluated regarding their particle size, zeta potential, conductivity,
      stability, viscosity, differential scanning calorimetry (DSC), scanning electron
      microscopy (SEM), refractory index (RI) and pH. RESULTS: The mean droplets size
      of microemulsion formulation were in the range of 7.03 to 79.8 nm, and its
      refractory index (RI) and pH were 1.45 and 6.75, respectively. Viscosity range
      was 253.73- 802.63cps. Drug release profile showed that 26.15% of the drug
      released in the first 24 hours of experiment. Also, Hexagonal and bicontinuous
      structures were seen in the SEM photograph of the microemulsions. CONCLUSION:
      characterization, physicochemical properties and in vitro release were dependent
      upon the contents of S/C ratio, water and, oil phase percentage in formulations.
      Also, ME-6 may be preferable for topical naproxen formulation.

PMID- 24312813
TI  - Diversity of Helicobacter Pylori cagA and vacA Genes and Its Relationship with
      Clinical Outcomes in Azerbaijan, Iran.
AB  - PURPOSE: The purpose of this research was to analyze cagA and vacA genotypes
      status in H. pylori isolates and relationship with clinical outcomes. METHODS:
      Gastric biopsy specimens were cultured for H. pylori isolation and cagA and vacA
      genes were detected in these isolates. Data were collected and the results were
      analyzed using chi2 and Fishers exact tests by SPSS software version. 16.
      RESULTS: Of the total 115 H. pylori isolates, 79 (68.7 %) were cagA positive and
      82 (71.3%) of isolates contained the s1 allele which 33 (28.7%) were subtype s2.
      s1m2 was the most frequent vacA allelic combination in the H. pylori isolates
      examined (63 cases), followed by s2m2 (31 cases), s1m1 (19 cases) and s2m1 (2
      case). Strains cagA positive were more frequent in peptic ulcer diseases patients
      than non ulcer diseases patients, as 47 (59.5%) and 32 (40.5%), while cagA
      negative were low, as 15 (41.7%) and 21 (58.3%), respectively. CONCLUSION: We
      found that the cagA and vacA status were not related to clinical outcomes in this
      area. Overall, in the present study, vacA s1/m2, cagA-positive strains were
      predominant irrespective of clinical outcome, but s2/m1 was rare.

PMID- 24312815
TI  - Comparison of Cytotoxic Activity of L778123 as a Farnesyltranferase Inhibitor and
      Doxorubicin against A549 and HT-29 Cell Lines.
AB  - PURPOSE: Farnesyltransferase (FTase) is a zinc-dependent enzyme that adds a
      farnesyl group to the Ras proteins. L778, 123 is a potent peptidomimetic
      imidazole-containing FTase inhibitor. METHODS: L778123 was synthesized according
      to known methods and evaluated alone and in combination with doxorubicin against
      A549 (adenocarcinomic human alveolar basal epithelial cells) and HT29 (human
      colonic adenocarcinoma) cell lines by MTT assay. RESULTS: L778123 showed weak
      cytotoxic activity with IC50 of 100 and 125 for A549 and HT-29 cell lines,
      respectively. The combination of doxorubicin and L778123 can decrease IC50 of
      doxorubicin in both cell lines significantly. CONCLUSION: It can be concluded
      that L778, 123 can be a good agent for combination therapy.

PMID- 24312816
TI  - Multivariate chemometric assisted analysis of metformin hydrochloride, gliclazide
      and pioglitazone hydrochloride in bulk drug and dosage forms.
AB  - PURPOSE: In this work a numerical method, based on the use of spectrophotometric
      data coupled to partial least squares (PLS) regression and net analyte
      preprocessing combined with classical least square (NAP/CLS) multivariate
      calibration, is reported for the simultaneous determination of metformin
      hydrochloride (MET), gliclazide (GLZ) and pioglitazone hydrochloride (PIO) in
      synthetic samples and combined commercial tablets. METHODS: Spectra of MET, GLZ
      and PIO were recorded at concentrations within their linear ranges (5-25 ug/ml,
      0.5-8 ug/ml and 0.5-3 ug/ml respectively) and were used to compute a total of 25
      synthetic mixtures involving 15 calibration and 10 validation sets between
      wavelength range of 200 and 400 nm in 0.1N HCl. The suitability of the models was
      decided on the basis of root mean square error (RMSE) values of calibration and
      validation data. RESULTS: The analytical performances of these chemometric
      methods were characterized by relative prediction errors and recovery studies (%)
      and were compared with each other. These two methods were successfully applied to
      pharmaceutical formulation, tablet, with no interference with excipients as
      indicated by the recovery study results. Mean recoveries of the commercial
      formulation set together with the figures of merit (calibration sensitivity,
      selectivity, limit of detection, limit of quantification etc.) were estimated.
      CONCLUSION: The proposed methods are simple, rapid and can be easily used as an
      alternative analysis tool in the quality control of drugs and formulation.

PMID- 24312817
TI  - Indomethacin electrospun nanofibers for colonic drug delivery: preparation and
      characterization.
AB  - PURPOSE: The objective of this study was to prepare a suitable form of nanofiber
      for indomethacin using polymers Eudragit RS100 (ERS) and Eudragit S100 (ES) and
      to evaluate the effect of some variables on the characteristics of resulted
      electrospunnanofibers. METHODS: Electrospinning process was used for preparation
      of nanofibers. Different solutions of combinations of ERS, ES and indomethacin in
      various solvents and different ratios were prepared. The spinning solutions were
      loaded in 10 mL syringes. The feeding rate was fixed by a syringe pump at 2.0
      mL/h and a high voltage supply at range 10-18 kV was applied for electrospinning.
      Electrospunnanofibers were collected and evaluated by scanning electron
      microscopy, differential scanning calorimetry and FTIR for possible interaction
      between materials used in nanofibers. The effect of solvent and viscosity on the
      characteristics of nanofibers also was investigated. RESULTS: Fiber formation was
      successful using a solvent ethanol and mixture of ERS and ES. Increase in
      viscosity of ethanolic solutions of ERS followed by addition of ES in the
      solution led to preparation of smooth fibers with larger diameters and less
      amounts of beads. DSC analysis of fibers certified that indomethacin is evenly
      distributed in the nanofibers in an amorphous state. FTIR analysis did not
      indicate significant interaction between drug and polymer. CONCLUSION: It was
      shown that drug-loaded ERS and ES nanofibers could be prepared by exact selection
      of range of variables such as type of solvent, drug: polymer ratio and solution
      viscosity and the optimized formulations could be useful for colonic drug
      delivery.

PMID- 24312818
TI  - Effect of Acute Administration of loganin on Spatial Memory in Diabetic Male
      Rats.
AB  - PURPOSE: Diabetes is associated with memory and learning disorder. The purpose of
      this study is to determine the effect of acute oral administration of loganin on
      memory in diabetic male rats. METHODS: 42 male Wistar rats (250-300 g) were
      divided into six groups: Control, Diabetic (1 week), Diabetic (12 weeks),
      Loganin, Diabetic (1 week) + Loganin, Diabetic (12 weeks) + Loganin. Diabetes was
      induced by IP injection of Streptozotocin (60 mg/kg). Loganin (40 mg/kg, po) was
      administrated 1 hour before test. Then, spatial memory was compared between
      groups with Morris Water Maze tests. RESULTS: Administration of loganin during
      acquisition, significantly (p<0.05) decreased both escape latency and traveled
      distance to find hidden platform in 1 and 12 weeks diabetic rats. In evaluation
      of recall phase of memory, loganin significantly (p<0.05) increased time and
      distance spent in the target quadrant in 1 and 12 weeks diabetic rats.
      CONCLUSION: Acute administration of loganin could improve spatial memory in
      diabetic rats.

PMID- 24312819
TI  - Toxicity effect of nigella sativa on the liver function of rats.
AB  - PURPOSE: The aim of this study was to determine the toxic effect of Nigella
      sativa powder on the liver function which was evaluated by measuring liver
      enzymes and through histopathological examination of liver tissue. METHODS:
      Twenty four male Sprague Dawley rats were allotted randomly to four groups
      including: control (taking normal diet); low dose (supplemented with 0.01
      g/kg/day Nigella sativa); normal dose (supplemented with 0.1 g/kg/day Nigella
      sativa) and high dose (supplemented with 1 g/kg/day Nigella sativa). All of
      supplements administered in powder form mixed with rats' pellet for 28 days. To
      assess liver toxicity, liver enzymes measurement and histological study were done
      at the end of supplementation. RESULTS: The finding revealed that there was no
      significant change in serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) between treatment groups. Histopathological study showed
      very minimal and mild changes in fatty degeneration in normal and high doses of
      Nigella sativa treated group. Inflammation and necrosis were absent. CONCLUSION:
      The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg
      supplemented for a period of 28 days resulted no changes in liver enzymes level
      and did not cause any toxicity effect on the liver function.

PMID- 24312820
TI  - Phytochemical Screening and Anti-nociceptive Properties of the Ethanolic Leaf
      Extract of Trema Cannabina Lour.
AB  - PURPOSE: The present study was designed to investigate the anti-nociceptive
      activity of ethanolic leaf extract of Trema cannabina Lour (family: Cannabaceae)
      in experimental animal models. METHODS: The anti-nociceptive action was carried
      out against two types of noxious stimuli, thermal (hot plate and tail immersion
      tests) and chemical (acetic acid-induced writhing) in mice. RESULTS:
      Phytochemical analysis of crude extract indicated the presence of reducing sugar,
      tannins, steroid and alkaloid types of secondary metabolites. Crude extract of T.
      cannabina (500 mg/kg dose) showed maximum time needed for the response against
      thermal stimuli (6.79+/-0.15 seconds) which is comparable to diclofenac sodium
      (8.26+/-0.14 seconds) in the hot plate test. Hot tail immersion test also showed
      similar results as in hot plate test. At the dose of 250 and 500 mg/kg body
      weight, the extract showed significantly and in a dose-dependent (p<0.001)
      reduction in acetic acid induced writhing in mice with a maximum effect of 47.56%
      reduction at 500 mg/kg dose comparable to that of diclofenac sodium (67.07%) at
      25 mg/kg. CONCLUSION: The obtained results tend to suggest the Anti-nociceptive
      activity of ethanolic leaf extract of Trema cannabina and thus provide the
      scientific basis for the traditional uses of this plant part as a remedy for
      pain.

PMID- 24312821
TI  - Mass-Production and Characterization of Anti-CD20 Monoclonal Antibody in
      Peritoneum of Balb/c Mice.
AB  - PURPOSE: Monoclonal antibodies are important tools are used in basic research as
      well as, in diagnosis, imaging and treatment of immunodeficiency diseases,
      infections and cancers. The purpose of this study was to produce large scale of
      monoclonal antibody against CD20 in order to diagnostic application in leukemia
      and lymphomas disorders. METHODS: Hybridoma cells that produce monoclonal
      antibody against human CD20 were administered into the peritoneum of the Balb/c
      mice which have previously been primed with 0.5 ml Pristane. After twelve days,
      approximately 7 ml ascetic fluid was harvested from the peritoneum of each mouse.
      Evaluation of mAb titration was assessed by ELISA method. In the present study,
      we describe a protocol for large scale production of MAbs. RESULTS: We prepared
      monoclonal antibodies (mAbs) with high specificity and sensitivity against human
      CD20 by hybridoma method and characterized them by ELISA. The subclass of
      antibody was IgG2a and its light chain was kappa. Ascetic fluid was purified by
      Protein-A Sepharose affinity chromatography and the purified monoclonal antibody
      was conjugated with FITC and Immunofluorescence was done for confirming the
      specific binding. CONCLUSION: The conjugated monoclonal antibody could have
      application in diagnosis B-cell lymphomas, hairy cell leukemia, B-cell chronic
      lymphocytic leukemia, and melanoma cancer stem cells.

PMID- 24312822
TI  - In vitro antioxidant and anticancer activity studies on drosera indica L.
      (Droseraceae).
AB  - PURPOSE: The aim of present in vitro studies was performed to examine the
      antioxidant and anticancer activities of ethanol and aqueous extracts of Drosera
      indica L. METHODS: Different concentrations (5 - 640mcg/ml) of the ethanol (EEDI)
      and aqueous (AEDI) extracts of D.indica L were used in various antioxidant assay
      methods such as hydroxyl radicals, DPPH, super oxide radical scavenging activity,
      chelating ability of ferrous ion, nitric oxide radical inhibition, ABTS and
      reducing power. Ascorbic acid (AA) was used as the standard antioxidant for the
      free radical scavenging assays. Dalton's Ascitic Lymphoma (DAL) and Ehrlich
      Ascitic Carcinoma (EAC) cell lines were used as the in vitro cancer models for
      the tryphan blue dye and LDH leakage assays, where 5 to 250mcg /ml of both EEDI
      and AEDI were tested. RESULTS: EEDI showed antioxidant activities with the
      minimum IC50 values of 34.8+/-0.43 mcg/ml in scavenging of hydroxyl radical and
      moreover AEDI showed minimum IC50 values of 94.51+/-0.84 mcg/ml in
      Fe(2+)chelating assay. EEDI on the reducing power assay and ABTS showed higher
      IC50 than standard AA. IC50 values of AEDI on Fe(2+) chelating assay and super
      oxide radical assay was lesser than IC50 value of AA. Both extracts at 250mcg/ml
      dose showed remarkable increase in the percentage of dead cancer cells (90% by
      EEDI and 86% by AEDI in DAL model and 89% by EEDI and 80% by AEDI in EAC model).
      CONCLUSION: It is concluded from this study that D.indica L exhibited excellent
      antioxidant activity against the different in vitro antioxidant models and
      anticancer activity against the two different cell lines tested.

PMID- 24312823
TI  - Comparison of in Vitro Activity of Doripenem versus Old Carbapenems against
      Pseudomonas Aeruginosa Clinical Isolates from both CF and Burn Patients.
AB  - PURPOSE: The antimicrobial activity of doripenem in comparison of imipenem,
      meropenem and ertapenem among Pseudomonas aeruginosa isolated from burn and
      Cystic Fibrosis (CF) patients were determined. METHODS: Metallo-beta-lactamase
      (MBL) genes in imipenem non susceptible P. aeruginosa isolates were detected
      using PCR method. The in vitro susceptibilities of doripenem, imipenem, meropenem
      and ertapenem were determined by Etests. MIC50 and MIC90 for corresponding
      antibiotics were determined individually in burn and CF isolates. RESULTS: Among
      isolates which were resistant to imipenem, 16 isolates were positive for the bla
      IMP gene. All isolates had no bla VIM gene. All MBL producing isolates were
      excluded. MIC50/MIC90 of doripenem in CF and burn isolates were 0.75/>32 and
      >32/>32 mg/L respectively. The corresponding values for imipenem in CF and burn
      isolates were 2/>32 and >32/>32 mg/L, respectively. CONCLUSION: The
      susceptibility rate of doripenem is higher than that of imipenem and meropenem
      among P.aeruginosa isolated from CF patients, whereas, there is no difference
      between the efficiency of doripenem and old carbapenems in non MBL producing
      P.aeruginosa isolates in burn patients.

PMID- 24312824
TI  - Comparison of inhibitory effect of curcumin nanoparticles and free curcumin in
      human telomerase reverse transcriptase gene expression in breast cancer.
AB  - PURPOSE: Telomerase is expressed in most cancers, including breast cancer.
      Curcumin, a polyphenolic compound that obtained from the herb of Curcuma longa,
      has many anticancer effects. But, its effect is low due to poor water solubility.
      In order to improve its solubility and drug delivery, we have utilized a beta
      cyclodextrin-curcumin inclusion complex. METHODS: To evaluate cytotoxic effects
      of cyclodextrin-curcumin and free curcumin, MTT assay was done. Cells were
      treated with equal concentration of cyclodextrin-curcumin and free curcumin.
      Telomerase gene expression level in two groups was compared by Real-time PCR.
      RESULTS: MTT assay demonstrated that beta-cyclodextrin-curcumin enhanced curcumin
      delivery in T47D breast cancer cells. The level of telomerase gene expression in
      cells treated with cyclodextrin-curcumin was lower than that of cells treated
      with free curcumin (P=0.001). CONCLUSION: RESULTS are suggesting that
      cyclodextrin-curcumin complex can be more effective than free curcumin in
      inhibition of telomerase expression.

PMID- 24312825
TI  - Detection of legionella contamination in tabriz hospitals by PCR assay.
AB  - PURPOSE: The present study was designed to evaluate the occurrence of Legionella
      contamination in the tap water of Tabriz hospitals, Azerbaijan, Iran. METHODS:
      One hundred and forty water samples from diverse water supply systems of 17
      hospitals were collected and analyzed for the presence of Legionella spp. by PCR
      assay. RESULTS: In this study, 10 of 140 (7.1%) samples were positive for
      Legionella which L. pneumophila was detected in 4 (2.85%) water samples.
      CONCLUSION: In conclusion, hospital potable systems are the primary reservoirs
      for Legionnaires' disease. This study concludes that Legionella spp. are present
      in aquatic hospitals environment of Tabriz. Due to the serious risk of
      infections, it is better to make efforts to eliminate Legionella spp. in water
      supplies.

PMID- 24312826
TI  - Cytoprotective Effects of Organosulfur Compounds against Methimazole Induced
      Toxicity in Isolated Rat Hepatocytes.
AB  - PURPOSE: Methimazole is a drug widely used in hyperthyroidism. However, life
      threatening hepatotoxicity has been associated with its clinical use. No
      protective agent has been found to be effective against methimazole induced
      hepatotoxicity yet. Hence, the capacity of organosulfur compounds to protect rat
      hepatocytes against cytotoxic effects of methimazole and its proposed toxic
      metabolite, N-methylthiourea was evaluated. METHODS: Hepatocytes were prepared by
      the method of collagenase enzyme perfusion via portal vein. Cells were treated
      with different concentrations of methimazole, N methylthiourea, and organosulfur
      chemicals. Cell death, protein carbonylation, reactive oxygen species formation,
      lipid peroxidation, and mitochondrial depolarization were assessed as toxicity
      markers and the role of organosulfurs administration on them was investigated.
      RESULTS: Methimazole caused a decrease in cellular glutathione content,
      mitochondrial membrane potential (DeltaPsim) collapse, and protein carbonylation.
      In addition, an increase in reactive oxygen species (ROS) formation and lipid
      peroxidation was observed. Treating hepatocytes with N methylthiourea caused a
      reduction in hepatocytes glutathione reservoirs and an elevation in carbonylated
      proteins, but no significant ROS formation, lipid peroxidation, or mitochondrial
      depolarization was observed. N-acetyl cysteine, allylmercaptan, and
      diallyldisulfide attenuated cell death and prevented ROS formation and lipid
      peroxidation caused by methimazole. Furthermore, organosulfur compounds
      diminished methimazole induced mitochondrial damage and reduced the carbonylated
      proteins. In addition, these chemicals showed protective effects against cell
      death and protein carbonylation induced by methimazole metabolite. CONCLUSION:
      Organosulfur chemicals extend their protective effects against methimazole
      induced toxicity by attenuating oxidative stress caused by this drug and
      preventing the adverse effects of methimazole and/or its metabolite (s) on
      subcellular components such as mitochondria.

PMID- 24312827
TI  - Effect of Aflatoxin B1 on Growth of Bovine Mammary Epithelial Cells in 3D and
      Monolayer Culture System.
AB  - PURPOSE: Many studies have been showed transfer of aflatoxins, toxins produced by
      Aspergillus flvaus and Aspergillus parasiticus fungi, into milk. These toxins are
      transferred into the milk through digestive system by eating contaminated food.
      Due to the toxicity of these materials, it seems that it has side effects on the
      growth of mammary cells. Therefore, the present work aimed to investigate
      possible toxic effects of aflatoxin B1 (AFB1) on bovine mammary epithelial cells
      in monolayer and three-dimensional cultures. METHODS: Specimens of the mammary
      tissue of bovine were sized out in size 2*2 cm in slaughterhouse. After
      disinfection and washing in sterile PBS, primary cell culture was performed by
      enzymatic digestion of tissue with collagenase. When proper numbers of cells were
      achieved in monolayer culture, cells were seeded in a 24-well culture plate for
      three-dimensional (3D) culture in Matrigel matrix. After 21 days of 3D culture
      and reaching the required number of cells, the concentrations of 15, 25 and 35 uL
      of AFB1 were added to the culture in quadruplicate and incubated for 8 hours.
      Cellular cytotoxicity was examined using standard colorimetric assay and finally,
      any change in the morphology of the cells was studied by microscopic technique.
      RESULTS: Microscopic investigations showed necrosis of the AFB1-exposed cells
      compared to the control cells. Also, bovine mammary epithelial cells were
      significantly affected by AFB1 in dose and time dependent manner in cell
      viability assays. CONCLUSION: According to the results, it seems that AFB1 can
      induce cytotoxicity and necrosis in bovine mammary epithelial cells.

PMID- 24312828
TI  - Thermoanalytical investigation of terazosin hydrochloride.
AB  - PURPOSE: Thermal analysis (TGA, DTG and DTA) and differential scanning
      calorimetry (DSC) have been used to study the thermal behavior of terazosin
      hydrochloride (TER). METHODS: Thermogravimetric analysis (TGA/DTG), differential
      thermal analysis (DTA) and differential scanning calorimetry (DSC) were used to
      determine the thermal behavior and purity of the used drug. Thermodynamic
      parameters such as activation energy (E*), enthalpy (?H*), entropy (?S*) and
      Gibbs free energy change of the decomposition (?G*) were calculated using
      different kinetic models. RESULTS: The purity of the used drug was determined by
      differential scanning calorimetry (99.97%) and specialized official method
      (99.85%) indicating to satisfactory values of the degree of purity. Thermal
      analysis technique gave satisfactory results to obtain quality control parameters
      such as melting point (273 oC), water content (7.49%) and ash content (zero) in
      comparison to what were obtained using official method: (272 oC), (8.0%) and
      (0.02%) for melting point, water content and ash content, respectively.
      CONCLUSION: Thermal analysis justifies its application in quality control of
      pharmaceutical compounds due to its simplicity, sensitivity and low operational
      costs. DSC data indicated that the degree of purity of terazosin hydrochloride is
      similar to that found by official method.

PMID- 24312829
TI  - Synthesis, characterization and antimicrobial activity of certain novel aryl
      hydrazone pyrazoline-5-ones containing thiazole moiety.
AB  - PURPOSE: The aim of this article is to synthesize, characterize and evaluate the
      antimicrobial activity of certain novel 3-methyl-5-oxo-4-(phenyl hydrazono)-4,5
      dihydro-pyrazol-1-yl]-acetic acid N|-(4-substituted thiazol-2-yl)-hydrazides.
      METHODS: The synthesized compounds were characterized by elemental analysis and
      IR, NMR and mass spectral data. The antimicrobial activity of novel compounds was
      evaluated by broth dilution method. RESULTS: XVe, XVf and XVg have shown better
      antibacterial activity than other compounds of the series. XVa, XVc, XVd and XVe
      have shown better antifungal activity than the other compounds of the series.
      CONCLUSION: All compounds were found to exhibit fair degree of antimicrobial
      activity.

PMID- 24312830
TI  - Effects of zinc supplementation on the anthropometric measurements, lipid
      profiles and fasting blood glucose in the healthy obese adults.
AB  - Purpose : The aim of this study was to assess the effects of zinc supplementation
      on anthropometric measures, improving lipid profile biomarkers, and fasting blood
      glucose level in obese people. METHODS: This randomized, double- blind clinical
      trial was carried out on 60 obese participants in the 18-45 age range for one
      month. The participants were randomly divided into the intervention group, who
      received 30 mg/d zinc gluconate, and the placebo group who received 30mg/d
      starch. Anthropometric measurements (body mass index (BMI), weight and waist
      circumference) were recorded before and at the end of study. Lipid profile
      biomarkers and fasting blood glucose were determined using enzymatic procedure.
      Analysis of Covariance (ANCOVA) test was run to compare the post-treatment values
      of the two groups, and t-test was conducted to compare within group changes.
      RESULTS: Serum zinc concentration was increased significantly in intervention
      group (p=0.024). BMI and body weight was significantly decreased (p=0.030 and
      p=0.020, respectively). Lipid profile biomarkers and fating blood glucose did not
      change significantly but triglyceride level was significantly decreased (p=0.006)
      in the intervention group. CONCLUSION: The obtained results indicate that zinc
      supplementation improves BMI, body weight, and triglyceride concentration without
      considerable effects on lipid profile and glucose level. Zinc can be suggested as
      a suitable supplementation therapy for obese people, but more studies are needed
      to verify the results.

PMID- 24312831
TI  - Protective Effect against Hydroxyl-induced DNA Damage and Antioxidant Activity of
      Radix Glycyrrhizae (Liquorice Root).
AB  - PURPOSE: As a typical Chinese herbal medicine, Radix Glycyrrhizae (RG) possesses
      various pharmacological effects involved in antioxidant ability. However, its
      antioxidant has not been explored so far. The aim of the study was to investigate
      its antioxidant ability, then further discuss the antioxidant mechanism. METHODS:
      RG was extracted by ethanol to obtain ethanolic extract of Radix Glycyrrhizae
      (ERG). ERG was then determined by various antioxidant methods, including DNA
      damage assay, DPPH assay, ABTS assay, Fe(3+)-reducing assay and Cu(2+)-reducing
      assay. Finally, the contents of total phenolics and total flavonoids were
      analyzed by spectrophotometric methods. RESULTS: Our results revealed that ERG
      could effectively protect against hydroxyl-induced DNA damage (IC50 517.28+/
      26.61MUg/mL). In addition, ERG could scavenge DPPH. radical (IC50165.18+/
      6.48MUg/mL) and ABTS(+)* radical (IC507.46+/-0.07MUg/mL), reduce Fe(3+) (IC50
      97.23+/-2.88 MUg/mL) and Cu(2+) (IC50 59.21+/-0.18 MUg/mL). Chemical analysis
      demonstrated that the contents of total phenolics and flavonoids in ERG were
      111.48+/-0.88 and 218.26+/-8.57 mg quercetin/g, respectively. CONCLUSION: Radix
      Glycyrrhizae can effectively protect against hydroxyl-induced DNA damage. One
      mechanism of protective effect may be radical-scavenging which is via donating
      hydrogen atom (H.), donating electron (e). Its antioxidant ability can be mainly
      attributed to the flavonoids or total phenolics.

PMID- 24312832
TI  - Protective Effect against Hydroxyl-induced DNA Damage and Antioxidant Activity of
      Citri reticulatae Pericarpium.
AB  - PURPOSE: As a typical Chinese herbal medicine, Citri reticulatae pericarpium
      (CRP) possesses various pharmacological effects involved in antioxidant ability.
      However, its antioxidant effects have not been reported yet. The objective of
      this work was to investigate its antioxidant ability, then further discuss the
      antioxidant mechanism. METHODS: CRP was extracted by ethanol to obtain ethanol
      extract of Citri reticulatae pericarpium (ECRP). ECRP was then measured by
      various antioxidant methods, including DNA damage assay, DPPH assay, ABTS assay,
      Fe(3+)-reducing assay and Cu(2+)-reducing assay. Finally, the content of total
      flavonoids was analyzed by spectrophotometric method. RESULTS: Our results
      revealed that ECRP could effectively protect against hydroxyl-induced DNA damage
      (IC50 944.47+/-147.74 MUg/mL). In addition, it could also scavenge DPPH. radical
      (IC50349.67+/-1.91 MUg/mL) and ABTS(+)* radical (IC5011.33+/-0.10 MUg/mL), reduce
      Fe(3+) (IC50 140.95+/-2.15 MUg/mL) and Cu(2+) (IC50 70.46+/-1.77 MUg/mL).
      Chemical analysis demonstrated that the content of total flavonoids in ECRP was
      198.29+/-12.24 mg quercetin/g. CONCLUSION: Citri reticulatae pericarpium can
      effectively protect against hydroxyl-induced DNA damage. One mechanism of
      protective effect may be radical-scavenging which is via donating hydrogen atom
      (H.), donating electron (e). Its antioxidant ability can be mainly attributed to
      the flavonoids, especially hesperidin and narirutin.

PMID- 24312833
TI  - High performance liquid chromatographic analysis of almotriptan malate in bulk
      and tablets.
AB  - PURPOSE: A simple RP-HPLC method has been developed and validated for the
      determination of almotriptan malate (ATM) in bulk and tablets. METHODS:
      Chromatographic separation of ATM was achieved by using a Thermo Scientific C18
      column. A Mobile phase containing a mixture of methanol, water and acetic acid
      (4:8:0.1 v/v) was pumped at the flow rate of 1 mL/min. Detection was performed at
      227 nm. According to ICH guidelines, the method was validated. RESULTS: The
      calibration curve was linear in the concentration range 5-60 ug/mL for the ATM
      with regression coefficient 0.9999. The method was precise with RSD <1.2%.
      Excellent recoveries of 99.60 - 100.80% proved the accuracy of the method. The
      limits of detection and quantification were found to be 0.025 and 0.075 ug/mL,
      respectively. CONCLUSION: The method was successfully applied for the
      quantification of ATM in tablets with acceptable accuracy and precision.

PMID- 24312834
TI  - Targeted fluoromagnetic nanoparticles for imaging of breast cancer mcf-7 cells.
AB  - PURPOSE: To achieve simultaneous imaging and therapy potentials, targeted
      fluoromagnetic nanoparticles were synthesized and examined in human breast cancer
      MCF-7 cells. METHODS: Fe3O4 nanoparticles (NPs) were synthesized through thermal
      decomposition of Fe(acac)3. Then, magnetic nanoparticles (MNPs) modified by
      dopamine-poly ethylene glycol (PEG)-NH2; finally, half equivalent fluorescein
      isothiocyanate (FITC) and half equivalent folic acid were conjugated to one
      equivalent of it. The presence of Fe3O4-DPA-PEG-FA/FITC in the folate receptor
      (FR) positive MCF-7 cells was determined via fluorescent microscopy to monitor
      the cellular interaction of MNPs. RESULTS: FT-IR spectra of final compound
      confirmed existence of fluorescein on folic acid grafted MNPs. The Fe3O4-DPA-PEG
      FA/FITC NPs, which displayed a size rang about 30-35 nm using scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM), were able to
      actively recognize the FR-positive MCF-7 cells, but not the FR-negative A549
      cells. CONCLUSION: The uniform nano-sized Fe3O4-DPA-PEG-FA/FITC NPs displayed
      great potential as theranostics and can be used for targeted imaging of various
      tumors that overexpress FR.

PMID- 24312835
TI  - Virulence and antimicrobial resistance in enterococci isolated from urinary tract
      infections.
AB  - PURPOSE: Urinary tract infection (UTI) is the most common nosocomial infection
      among hospitalized patients. Meanwhile, most frequent infections involving
      enterococci affect the urinary tract. The aims of this study were to investigate
      the susceptibility pattern of isolated enterococci from UTI and the prevalence of
      virulence genes. METHODS: The study used enterococci isolated from urinary tract
      infections obtained from 3 university teaching hospitals in Northwest Iran. The
      antimicrobial susceptibility of the strains was determined using the disc
      diffusion method. Multiplex PCR was performed for the detection of genus- species
      specific targets, and potential virulence genes. RESULTS: Of 188 enterococcal
      isolates, 138 (73.4%) and 50 (26.6%) were Enterococcus faecalis and E. faecium,
      respectively. Antibiotic susceptibility testing showed high resistance to
      amikacin (86.2%), rifampicin (86.2%) and erythromycin (73.9%), irrespective of
      species. In total, 68.1% were positive for gelE, and 57.4%, 53.2%, 56.4%, and
      52.1% of isolates were positive for cpd, asa1, ace, and esp, respectively.
      CONCLUSION: The study revealed that most of UTI isolates were multidrug
      resistance against the antibiotics tested and antibiotic resistance was more
      common among E. faecium isolates than E. faecalis. A significant correlation was
      found between UTI and the presence of gelE among E. faecalis strains (p < 0.001).

PMID- 24312836
TI  - Dose-Dependent Effect of Flouxetine on 6-OHDA-Induced Catalepsy in Male Rats: A
      Possible Involvement of 5-HT1A Receptors.
AB  - PURPOSE: Progressive loss of dopaminergic neurons of the substantia nigra pars
      compacta (SNc) in Parkinson's disease (PD) leads to impairment of motor skills.
      Several evidences show that the role of serotonergic system in regulation of
      normal movement is pivotal and mediates via 5-HT1A receptors. Our previous study
      has shown that fluoxetine in acute injections able to attenuate catalepsy in 6
      hydroxydopamine (6-OHDA)-lesioned rats. Since drugs are used chronically in
      clinic, in this study we attempted to evaluate effect of chronic administration
      of fluoxetine on 6-OHDA-induced catalepsy. METHODS: Catalepsy was induced by
      unilateral infusion of 6-OHDA (8 ug/2 ul/rat) into the central region of SNc and
      assayed by using bar-test. Fluoxetine (1, 2.5, 5 and 10 mg/kg) was injected
      intraperitonealy (ip) for 10 days and its anti-cataleptic effect was assessed at
      the 10th day. RESULTS: Fluoxetine in high doses (5 and 10 mg/kg) worsened 6-OHDA
      induced catalepsy while it had anti-cataleptic effect at the dose of 1mg/kg. The
      anti-cataleptic effect of fluoxetine (1mg/kg) was reversed by co-administration
      with NAN-190 (0.5 mg/kg, ip), as a5-HT1Areceptor antagonist. CONCLUSION:
      According to the results it can be concluded that fluoxetine has anti-cataleptic
      effect in parkinsonian rats only at low doses, whereas at higher doses it worsens
      catalepsy. It's anti-cataleptic effect is exerted through affecting on 5
      HT1Areceptors. However, at high doses other mechanisms may be involved. Further
      clinical studies are needed to prove it's possible clinical application as an
      adjuvant therapy in reducing catalepsy of PD.

PMID- 24312837
TI  - Hypoglycemic Activity of Fumaria parviflora in Streptozotocin-Induced Diabetic
      Rats.
AB  - PURPOSE: Fumaria parviflora Lam (Fumariaceae) has been used in traditional
      medicine in the treatment of several diseases such as diabetes. The present work
      was designed to evaluate the hypoglycaemic effects of methanolic extract (ME) of
      F. parviflora in normal and streptozotocin-induced diabetic rats. METHODS: The
      rats used were allocated in six (I, II, III, IV, V and VI) experimental groups
      (n=5). Group I rats served as 'normal control' animals received distilled water
      and group II rats served as 'diabetic control' animals. Diabetes mellitus was
      induced in groups II, V and VI rats by intraperitoneal single injection of
      streptozotocin (STZ, 55 mg kg-1). Group V and VI rats were addi-tionally treated
      with ME (150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively) 24 hour post
      STZ injection, for seven consecutive days. Groups III and IV rats received only
      ME 150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively for seven days. The
      levels of blood glucose were determined using a Glucometer. RESULTS: Administra
      tion of F. parviflora extract showed a potent glucose lowering effect only on
      streptozo-tocin (STZ) induced diabetic rats below 100 mg/dl (P<0.001). However,
      no significant differences in the blood glucose levels were recorded between
      diabetic rats received 125 or 250 mg/kg of plant extracts. CONCLUSION: The
      findings of the study indicated that F. parviflora has significant hypoglycemic
      effect on STZ-induced diabetic rats with no effects on blood glucose levels of
      normal rats.

PMID- 24312838
TI  - Large Scale Generation and Characterization of Anti-Human CD34 Monoclonal
      Antibody in Ascetic Fluid of Balb/c Mice.
AB  - PURPOSE: Monoclonal antibodies or specific antibodies are now an essential tool
      of biomedical research and are of great commercial and medical value. The purpose
      of this study was to produce large scale of monoclonal antibody against CD34 in
      order to diagnostic application in leukemia and purification of human
      hematopoietic stem/progenitor cells. METHODS: For large scale production of
      monoclonal antibody, hybridoma cells that produce monoclonal antibody against
      human CD34 were injected into the peritoneum of the Balb/c mice which have
      previously been primed with 0.5 ml Pristane. 5 ml ascitic fluid was harvested
      from each mouse in two times. Evaluation of mAb titration was assessed by ELISA
      method. The ascitic fluid was examined for class and subclasses by ELISA mouse
      mAb isotyping Kit. mAb was purified from ascitic fluid by affinity chromatography
      on Protein A-Sepharose. Purity of monoclonal antibody was monitored by SDS -PAGE
      and the purified monoclonal antibody was conjugated with FITC. RESULTS:
      Monoclonal antibodies with high specificity and sensitivity against human CD34 by
      hybridoma technology were prepared. The subclass of antibody was IgG1 and its
      light chain was kappa. CONCLUSION: The conjugated monoclonal antibody could be a
      useful tool for isolation, purification and characterization of human
      hematopoietic stem cells.

PMID- 24312839
TI  - Formulation, characterization and physicochemical evaluation of potassium citrate
      effervescent tablets.
AB  - PURPOSE: The aim of this study was to design and formulation of potassium citrate
      effervescent tablet for reduction of calcium oxalate and urate kidney stones in
      patients suffering from kidney stones. METHODS: In this study, 13 formulations
      were prepared from potassium citrate and effervescent base in different
      concentration. The flowability of powders and granules was studied. Then
      effervescent tablets were prepared by direct compression, fusion and wet
      granulation methods. The prepared tablets were evaluated for hardness,
      friability, effervescent time, pH, content uniformity. To amend taste of
      formulations, different flavoring agents were used and then panel test was done
      by using Latin Square method by 30 volunteers. RESULTS: Formulations obtained
      from direct compression and fusion methods had good flow but low hardness. Wet
      granulation improves flowability and other physicochemical properties such as
      acceptable hardness, effervescence time <=3 minutes, pH<6, friability < 1%, water
      percentage < 0.5% and accurate content uniformity. In panel test, both of
      combination flavors; (orange - lemon) and (strawberry - raspberry) had good
      acceptability. CONCLUSION: The prepared tablets by wet granulation method using
      PVP solution had more tablet hardness. It is a reproducible process and suitable
      to produce granules that are compressed into effervescent tablets due to larger
      agglomerates.

PMID- 24312840
TI  - Synthesis and antimicrobial evaluation of certain novel thiazoles.
AB  - PURPOSE: This article makes an attempt to synthesize certain compounds containing
      thiazole and imidazole moieties and screen for the antimicrobial properties.
      METHODS: The novel compounds synthesized were characterized by elemental
      analysis, IR and (1)HNMR spectral data. The antimicrobial activity of novel
      compounds was evaluated by cup plate method. RESULTS: The compound p-t showed
      more antibacterial activity than that of the standard. p-hp and p-as showed
      considerable antibacterial activity. p-t demonstrated higher antifungal activity
      than that of the standard while p-hp and p-as showed considerable antifungal
      activity. CONCLUSION: The antimicrobial activity studies were conducted on
      certain selected bacteria and fungi. In each case antimicrobial activity of the
      compounds was compared with that of standards. p-t, p-hp, p-np, p-cp, p-ts and p
      as showed considerable antimicrobial activity.

PMID- 24312841
TI  - Extractive spectrophotometric determination of ambrisentan.
AB  - PURPOSE: Ambrisentan (ABS) is an antihypertensive drug used in the treatment of
      pulmonary atrial hypertension. The survey of literature for ABS revealed only two
      spectrophotometric methods for its quantification. The reported methods lack the
      sensitivity. This study is aimed at developing two sensitive extractive
      spectrophotometric methods for the determination of ABS in bulk and in tablets.
      METHODS: The proposed methods are based on the formation of colored chloroform
      extractable ion-pair complexes of ABS with methylene blue (MB method) and
      safranine O (SO method) in buffered solution at pH 9.8. The extracted complexes
      showed maximum absorbance at 525 and 515 nm for methylene blue and safranine O,
      respectively. RESULTS: In both the methods, the calibration curve was linear from
      1-15 ug mL(-1) of drug. Apparent molar absorpitivities were 1.7911 x 10(5),
      2.3272 x 10(5) L mol(-1) cm(-1); Sandell's sensitivities were 0.0215, 0.0162 ug
      cm(-2); LOD were 0.182, 0.175 ug mL(-1); LOQ were 0.551, 0.531 ug mL(-1) for
      methods MB and SO, respectively. The relative standard deviation and percent
      recovery ranged from 0.206-1.310% and 99.0-101.5%, respectively. CONCLUSION: The
      results demonstrate that the proposed methods are sensitive, precise, accurate
      and inexpensive. These methods can easily be used for the assay of ABS in quality
      control laboratories.

PMID- 24312842
TI  - Combination Studies of Oreganum Vulgare Extract Fractions and Volatile Oil along
      with Ciprofloxacin and Fluconazole against Common Fish Pathogens.
AB  - PURPOSE: The study is aimed at finding new antibiotic therapy for aquaculture due
      to potential of bacteria to develop resistance to the existing therapies. Use of
      large quantities of synthetic antibiotics in aquaculture thus has the potential
      to be detrimental to fish health, to the environment and wildlife and to human
      health. METHODS: Antimicrobial potential of volatile oil and fractions of
      chloroform extract of Oreganum vulgare was evaluated alone and in the presence of
      standard antimicrobials against common fish pathogens by disc-diffusion, agar
      well assay and two fold microdilution method by nanodrop spectrophotometric
      method. RESULTS: The best results were represented by volatile oil followed by
      phenolic fraction by disc-diffusion, agar well and microdilution assays (Minimum
      inhibitory concentration). By the interaction studies, it was observed that the
      volatile oil and phenolic fraction were able to inhibit the pathogens at very low
      concentration compared to standard drugs. The fractional inhibitory concentration
      index (FICI) was calculated and volatile oil and phenolic fractions were found to
      be synergistic against Pseudomonas fluorescens and Candida albicans. CONCLUSION:
      The experimental data suggests the use of volatile oil and phenolic fraction in
      combination with standard antimicrobials to maintain healthy aquaculture with
      lesser adverse effects as compared to synthetic antibiotic therapy.

PMID- 24312843
TI  - Skin infection management using novel antibacterial agents.
AB  - Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA)
      cause difficulties in the management of skin and soft tissue infections and have
      led to morbidity and mortality in hospital-acquired infections especially in
      susceptible individuals, those who are generally sick or immunosuppressed.
      Currently approaches in antibacterial agents offer opportunities to manage the
      trouble using novel anti-infection systems. Therefore, nanotechnology, a most
      promising field for generating new applications in medicine, has introduced a
      most prominent nanoproduct named as nanosilver that revealed excellent
      antimicrobial activity against some of the hazardous infections. Also
      cathelicidin peptides which are a part of native immune defense system in the
      skin and epithelia exhibit excellent antimicrobial activity against some of these
      perilous infections. 

PMID- 24312844
TI  - Gene therapy, early promises, subsequent problems, and recent breakthroughs.
AB  - Gene therapy is one of the most attractive fields in medicine. The concept of
      gene delivery to tissues for clinical applications has been discussed around half
      a century, but scientist's ability to manipulate genetic material via recombinant
      DNA technology made this purpose to reality. Various approaches, such as viral
      and non-viral vectors and physical methods, have been developed to make gene
      delivery safer and more efficient. While gene therapy initially conceived as a
      way to treat life-threatening disorders (inborn errors, cancers) refractory to
      conventional treatment, to date gene therapy is considered for many non-life
      threatening conditions including those adversely influence on a patient's quality
      of life. Gene therapy has made significant progress, including tangible success,
      although much slower than was initially predicted. Although, gene therapies still
      at a fairly primitive stage, it is firmly science based. There is justifiable
      hope that with enhanced pathobiological understanding and biotechnological
      improvements, gene therapy will be a standard part of clinical practice within 20
      years. 

PMID- 24312845
TI  - Gene expression in Mammalian cells and its applications.
AB  - The production of proteins in appropriate quantity and quality is an essential
      requirement of the present time. There appears to be a progressive increase in
      the application of mammalian cells for proteins production. Expression systems
      utilizing mammalian cells for recombinant proteins are able to introduce proper
      protein folding, post-translational modifications, and product assembly, which
      are important for complete biological activity. This review article is totally
      based on literature survey. In this article much emphasis has been done on the
      mammalian expression system. The author focused on different mammalian cell lines
      that express the gene. The different vector systems that transfer the gene into
      mammalian cells like plasmid based expression vectors, adenovirus vectors,
      vaccinia vectors, retroviral vector and baculovirus as vectors were explored. The
      processes for the transfer of gene into mammalian cells were also reviewed.
      Application and limitations of mammalian expression system were also focused. The
      purpose of research in writing this article is to create awareness in
      researchers, starting their career in gene expression related to mammalian cells.
      The principal result and major conclusion of this article is to make available
      the molecular technologies, expression system and applications of gene expression
      in mammalian cell lines. 

PMID- 24312848
TI  - Oreganum vulgare Linn. leaf: An Extensive Pharmacognostical and Phytochemical
      Quality Assessment.
AB  - PURPOSE: Standardization and detailed pharmacognostical studies of Oreganum
      vulgare Linn. leaf for authentication and commercial utilization. METHODS:
      Oreganum vulgare Linn. leaf was with standardization according to standard
      procedures described in WHO, 2011 and I.P. 1996. RESULTS: The physicochemical
      parameters total ash, acid insoluble ash, water soluble ash and sulphated ash
      were found to be 11.5%, 11%, 5, 10.5% w/w respectively. Foaming index was found
      be <100. The trace elements were found to be copper, lead, cadmium, zinc, cobalt,
      manganese, nickel and copper in ethanol extract and phytochemical screening of
      aqueous and ethanol extract showed the presence of carbohydrates, flavonoids,
      anthocyanins, phenolic compounds etc. CONCLUSION: The standardization parameters
      viz. physico-chemical parameters, macroscopy, microscopy, taxonomy, anatomy and
      preliminary phytochemical screening, microbial and aflatoxin count, HPTLC profile
      is being reported to help in authentication and development of monograph of this
      plant.

PMID- 24312846
TI  - NPY Receptors Blockade Prevents Anticonvulsant Action of Ghrelin in the
      Hippocampus of Rat.
AB  - PURPOSE: Ghrelin has been shown to have antiepileptic function. However, the
      underlying mechanisms by which, ghrelin exerts its antiepileptic effects are
      still unclear. In the present study, we investigated whether neuropeptide Y (NPY)
      mediates ghrelin anticonvulsant effect in the brain through its Y1, Y2 or Y5
      receptors. METHODS: Male Wistar rats were bilaterally microinjected with ghrelin
      0.3 nmol/MUl/side and NPY antagonists; GR231118 (Y1 receptor antagonist),
      BIIE0246 (Y2 receptor antagonist), CGP71683 (Y5 receptor antagonist) or solvents
      (Saline, DMSO) into the dorsal hippocampus 20 minutes before ghrelin
      administration. Thirty minutes after ghrelin microinjection, a single convulsive
      dose of pentylenetetrazole (PTZ) (50 mg/kg) was injected intraperitoneally (ip).
      Afterwards, duration of seizure and total seizure score (TSS) were assessed for
      30 minutes in all animals. RESULTS: Intrahippocampal injection of 0.3
      nmol/MUl/side ghrelin decreased duration of seizure and TSS induced by PTZ. The
      suppression of both duration (p<0.001) and TSS (p<0.001) induced by ghrelin in
      hippocampus were significantly blocked by GR231118 (10 MUg/MUl/side), BIIE0246
      (400 pmol/MUl/side) and CGP 71683A (5 nmol/MUl/side). CONCLUSION: Our findings
      suggest that NPY Y1, Y2 and Y5 receptors in the hippocampus may somehow mediate
      the anticonvulsive action of ghrelin. Therefore, it is possible to speculate that
      ghrelin acts in the hippocampus to modulate seizures via NPY.

PMID- 24312847
TI  - Anti-inflammatory effects of zingiber officinale in type 2 diabetic patients.
AB  - PURPOSE: Low-grade inflammation, a common feature in type 2 diabetes (DM2),
      causes some chronic complications in these patients. The present study was aimed
      to evaluate the effects of ginger (Zingiber officinale) on pro-inflammatory
      cytokines (IL-6 and TNF-alpha) and the acute phase protein hs-CRP in DM2 patients
      as a randomized double-blind placebo controlled trial. METHODS: A total of 64 DM2
      patients randomly were assigned to ginger or placebo groups and received 2
      tablets/day of each for 2 months. The concentrations of IL-6, TNF-alpha and hs
      CRP in blood samples were analyzed before and after the intervention. RESULTS:
      Ginger supplementation significantly reduced the levels of TNF-alpha (P = 0.006),
      IL-6 (P = 0.02) and hs-CRP (P = 0.012) in ginger group in comparison to baseline.
      Moreover, the analysis of covariance showed that the group received ginger
      supplementation significantly lowered TNF- alpha (15.3 +/- 4.6 vs. 19.6 +/- 5.2;
      P = 0.005) and hs-CRP (2.42 +/- 1.7 vs. 2.56 +/- 2.18; P = .016) concentrations
      in comparison to control group. While there were no significant changes in IL-6
      (7.9 +/- 2.1 vs. 7.8 +/- 2.9; P > .05). CONCLUSION: In conclusion, ginger
      supplementation in oral administration reduced inflammation in type 2 diabetic
      patients. So it may be a good remedy to diminish the risk of some chronic
      complications of diabetes.

PMID- 24312849
TI  - Effect of vitamin b6 on clinical symptoms and electrodiagnostic results of
      patients with carpal tunnel syndrome.
AB  - PURPOSE: Carpal tunnel syndrome (CTS) refers to a cluster of signs and symptoms
      that stems from compression of the median nerve traveling through carpal tunnel.
      Surgery is a definite treatment for CTS; however, many conservative therapies
      have been proposed. The present study set out to assess the effect of vitamin B6
      in patients with CTS. METHODS: Forty patients (67 hands) with mild-moderate CTS
      were initially selected and randomly assigned into two groups as follows: 1) Case
      group with 20 subjects (32 affected hands) receiving vitamin B6 (120 mg/day for 3
      months) and splinting. 2) Control group with 19 subjects (35 affected hands) only
      received splinting. One subject from the control group dispensed with continuing
      participation in the research. Daily symptoms and electrodiagnostic (NCV-EMG)
      results were assessed at baseline and after 3 months. RESULTS: Nocturnal
      awakening frequency due to pain, daily pain, daily pain frequency, daily pain
      persistence, hand numbness, hand weakness, hand tingling, severity of nocturnal
      numbness and tingling, nocturnal awakening frequency owing to hand numbness and
      tingling, and clumsiness in handling objects improved significantly in the
      vitamin B6-treated patients; even so, only problem with opening a jam bottle and
      handling phone significantly reduced in the control group. The median nerve
      sensory latency mean decreased following the treatment; and the median nerve
      sensory amplitude mean and sensory conduction velocity mean increased.
      CONCLUSION: The present study suggests that vitamin B6 treatment improves
      clinical symptoms and sensory electrodiagnostic results in CTS patients, and thus
      is recommended for CTS treatment.

PMID- 24312850
TI  - Development and application of an HPLC method for erlotinib protein binding
      studies.
AB  - PURPOSE: The aim of the present study was to develop a simple and rapid reversed
      phase high performance liquid chromatographic method with UV detection for
      erlotinib hydrochloride quantification, which is applicable for protein binding
      studies. METHODS: Ultrafilteration method was used for protein binding study of
      erlotinib hydrochloride. For sample analysis a simple and rapid reversed-phase
      high performance liquid chromatographic method with UV detection at 332 nm was
      developed. The mobile phase was a mixture of methanol, acetonitril and potassium
      dihydrogen phosphate buffer (15:45:40 %v/v) set at flow rate of 1.3 ml/min.
      RESULTS: The run time for erlotinib hydrochloride was approximately 6 minutes.
      The calibration curve was linear over the range of 320-20000 ng/ml with
      acceptable intra- and inter-day precision and accuracy. The intra-day and inter
      day precisions were less than 10% and the accuracies of intra and inter-day
      assays were within the range of 97.20-104.83% and 98.8-102.2% respectively.
      CONCLUSION: Based on the obtained results, a simple, accurate and precise
      reversed-phase isocratic HPLC method with UV detection has been optimized and
      validated for the determination of erlotinib hydrochloride in biological samples.

PMID- 24312851
TI  - Percutaneous absorption of salicylic Acid after administration of trolamine
      salicylate cream in rats with transcutol((r)) and eucalyptus oil pre-treated
      skin.
AB  - PURPOSE: This study was conducted to assess the effect of skin pre-treatment with
      Transcutol((r)) and eucalyptus oil on systemic absorption of topical trolamine
      salicylate in rat. METHODS: Pharmacokinetic parameters of salicylic acid
      following administration of trolamine salicylate on rat skin pre-treated with
      either Transcutol((r)) or eucalyptus oil were determined using both non
      compartmental and non-linear mixed effect modeling approaches and compared with
      those of control group. RESULTS: Median (% of interquartile range/median) of
      salicylic acid AUC0-8hr (ng/mL/hr) values in Transcutol((r)) or eucalyptus oil
      treated rats were 2522(139%) and 58976(141%), respectively as compared to the
      3023(327%) of the control group. Skin pre-treatment with eucalyptus oil could
      significantly decrease extravascular volume of distribution (V/F) and elimination
      rate constant (k) of salicylic acid. CONCLUSION: Unlike Transcutol((r)),
      eucalyptus oil lead to enhanced transdermal absorption of trolamine salicylate
      through rat skin.

PMID- 24312852
TI  - Construction of pPIC9 Recombinant Vector Containing Human Stem Cell Factor.
AB  - PURPOSE: Various cytokine regulates hematopoesis; they promote number of stages
      in stem cells biology such as proliferation, differentiation and endurance.
      Biological effects of SCF, as a hematopoietic cytokine; is triggered by binding
      to its ligand c-kit. Potential therapeutic applications of SCF include
      hematopoietic stem cell mobilization, exvivo stem/progenitor cell expansion, gene
      therapy, and immunotherapy. In this study we tried to construct of pPIC9
      recombinant vector containing human SCF. METHODS: hSCF cDNA was amplified by PCR
      and both hSCF cDNA and pPIC9 as yeast expression vector (shuttle vector) digested
      by EcoR I and Xho I restriction enzymes. Subsequent the digestion reaction,
      ligation reaction was carried out. In order to verifying of pPIC9 recombinant
      vector containing hSCF, PCR and sequence analysis was performed. RESULTS: The
      construction of recombinant expression vector of pPIC9 containing hSCF cDNA was
      confirmed by sequencing method successfully. CONCLUSION: rhSCF/pPIC9 vector can
      be transformed into the Picha pastoris yeast as a eukaryotic host in order to
      produce human SCF at industrial scale.

PMID- 24312853
TI  - Cadmium-induced toxicity and the hepatoprotective potentials of aqueous extract
      of jessiaea nervosa leaf.
AB  - PURPOSE: Hepatoprotective potentials of Jussiaea nervosa leaf extract against
      Cadmium-induced hepatotoxicity were investigated. METHODS: Forty albino rats were
      randomly assigned into groups A-G with 4 rats in each of the groups A-F. Group A
      served as control and were given feed only while rats in groups B-F were orally
      exposed to varying concentrations of cadmium for six weeks. Effects of cadmium
      were most significant at 12 mg/Kg body weight (BW), and this dose was used for
      subsequent test involving oral administration of Jussiaea nervosa leaf extracts.
      In this segment, group G (n= 16) was sub-divided into four: G1-G4, with each sub
      group containing four rats. Rats in sub-group G1 were given cadmium and feed only
      and served as positive control. Rats in sub-groups G2, G3, and G4 were given
      cadmium and 20, 50 and 100g/kg BW of Jussiaea nervosa extract, respectively, for
      six weeks. Blood and liver were analysed using standard laboratory techniques and
      methods. RESULTS: Liver function parameters (ALT, AST, ALP, bilirubin) were
      significantly (p<0.05) elevated in exposed rats in comparison to the controls,
      except for total protein and albumin, which were significantly decreased.
      Histopathological assessment reveals renal pathology in exposed rats in sharp
      contrast with the controls. Jussiaea nervosa extract however lowered the values
      of liver function parameters with 100mg/Kg BW dose producing the highest
      ameliorative effects. Similarly, the serum albumin and total protein
      significantly (p<0.05) improved with normal liver architecture. CONCLUSION: The
      results show the hepatoprotective potentials of Jussiaea nervosa extract against
      Cd toxicity.

PMID- 24312854
TI  - Formulation, characterization and physicochemical evaluation of ranitidine
      effervescent tablets.
AB  - PURPOSE: The aim of this study was to design, formulate and physicochemically
      evaluate effervescent ranitidine hydrochloride (HCl) tablets since they are
      easily administered while the elderly and children sometimes have difficulties in
      swallowing oral dosage forms. METHODS: Effervescent ranitidine HCl tablets were
      prepared in a dosage of 300 mg by fusion and direct compression methods. The
      powder blend and granule mixture were evaluated for various pre-compression
      characteristics, such as angle of repose, compressibility index, mean particle
      size and Hausner's ratio. The tablets were evaluated for post-compression
      features including weight variation, hardness, friability, drug content,
      dissolution time, carbon dioxide content, effervescence time, pH, content
      uniformity and water content. Effervescent systems with appropriate pre and post
      compression qualities dissolved rapidly in water were selected as the best
      formulations. RESULTS: The results showed that the flowability of fusion method
      is more than that of direct compression and the F5 and F6 formulations of 300 mg
      tablets were selected as the best formulations because of their physicochemical
      characteristics. CONCLUSION: In this study, citric acid, sodium bicarbonate and
      sweeteners (including mannitol, sucrose and aspartame) were selected. Aspartame,
      mint and orange flavors were more effective for masking the bitter taste of
      ranitidine. The fusion method is the best alternative in terms of physicochemical
      and physical properties.

PMID- 24312855
TI  - Protective Role of GnRH Antagonist on Chemotherapy-induced Spermatogenesis
      Disorder: A Morphological Study.
AB  - PURPOSE: Anti cancer drugs is one of the most important chemotherapeutic factors
      which can influence spermatogenesis process and germinal epithelium. Since
      dividing cells are mainly affected by anticancer drugs, the aim of the present
      study is to investigate the preventive effect of GnRH antagonist on spermatogenic
      defect produced by anticancer drugs. METHODS: In the present study thirty adult
      male mice aging 6-8 weeks were divided into 3 groups as: Control, Experimental 1
      and Experimental 2. Experimental 1 group received Cisplatin for 5 days as 2.5
      mg/kg intraperitoneally and Experimental 2 group received 0.25 mg/kg cetrorelix
      (GnRH antagonist) one week before cisplatin treatment and continued for 3 weeks.
      The mice in all groups were sacrificed 35 days after the last injection and
      testis specimens were fixed in boueins, formaldehyde fixative and 2.5%
      Glutaraldehide then prepared for light and electron microscopic examination.
      RESULTS: Light microscopy (LM) study showed that the number of spermatogonial
      cells, thickness of germinal epithelium, was decreased in Experimental 1group.
      Electron microscopy revealed that in this group several intercellular spaces
      appeared between spermatogenic cells and secretory granules in interstitial cells
      was increased. There were several vacuolated mitochondria and destroyed
      organelles in spermatogonial cells but in Experimental 2 group condition was
      similar to control group. CONCLUSION: These results indicate that the cetrorelix
      administration before cancer treatment may protect germinal epithelium against
      side effects of cisplatin.

PMID- 24312856
TI  - Induction of CD14 Expression and Differentiation to Monocytes or Mature
      Macrophages in Promyelocytic Cell Lines: New Approach.
AB  - PURPOSE: CD14, one of the main differentiation markers on the surface of myeloid
      lineage cells, acts as a key role in activation of LPS-induced monocytes. LPS
      (lipopolysaccharide) binds to LPS-binding protein in plasma and are delivered to
      the cell surface receptor CD14. In this study, Various stimuli [Dimethyl
      Sulfoxide (DMSO), active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and LPS], either
      alone or in combination, have been recognized that have an effect on the level of
      CD14 expression in the human HL-60 and U937 promonocytic cell lines and therefore
      induce their terminal differentiation into monocytes or mature macrophages.
      METHODS: U937 and HL-60 cells were cultured in RPMI 1640 supplemented with 10%
      FBS. For each cell line, 1A106 cells were seeded for 72 hours with DMSO, 14 days
      with LPS and 18 days with 1, 25-D3 in each well plate; then ELISA method was used
      to study their responses to the factors by means of anti-CD14. RESULTS: ELISA
      assay demonstrated that U937 and HL-60 cells were induced by both [1,25(OH)2D3]
      and DMSO to obtain characteristics of adherent cells and express CD14 protein;
      moreover, LPS at a low dose increased CD14 expression on surface of this cells.
      CONCLUSION: According to the our results, it is speculated that CD14 gene
      expression may be induced in human U937 and HL-60 cell lines by different factors
      including 1,25-D3, DMSO and LPS.

PMID- 24312857
TI  - A unique report: development of super anti-human IgG monoclone with optical
      density over than 3.
AB  - PURPOSE: Monoclonal antibodies and related conjugates are key reagents used in
      biomedical researches as well as, in treatment, purification and diagnosis of
      infectious and non- infectious diseases. METHODS: Balb/c mice were immunized with
      purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0
      in the presence of Poly Ethylene Glycol (PEG). Supernatant of hybridoma cells was
      screened for detection of antibody by ELISA. Then, the sample was assessed for
      cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The
      subclasses of the selected mAbs were determined. The best clone was injected
      intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from
      the animals' ascitic fluid by Ion exchange chromatography and then, mAb was
      conjugated with HRP. RESULTS: In the present study, over than 50 clones were
      obtained that 1 clone had optical density over than 3. We named this clone as
      supermonoclone which was selected for limiting dilution. The result of the
      immunoblotting, showed sharp band in IgG position and did not show any band in
      IgM&IgA position. CONCLUSION: Based on the findings of this study, the conjugated
      monoclonal antibody could have application in diagnosis of infectious diseases
      like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious
      diseases.

PMID- 24312858
TI  - Electrochemical studies for the determination of quetiapine fumarate and
      olanzapine antipsychotic drugs.
AB  - PURPOSE: Cyclic voltammetry and differential pulse voltammetry were used to
      explore the diffusion behavior of two antipsychotic drugs at a glassy carbon
      electrode. A well-defined oxidation peak was obtained in Britton-Robinson (BR)
      buffer (pH 2.0). The response was evaluated as a function of some variables such
      as the scan rate, and pH. METHODS: A simple, precise, inexpensive and sensitive
      voltammetric method has been developed for the determination of the cited drugs
      Olanzapine (OLZ) and Quetiapine fumarate (QUT). RESULTS: A linear calibration was
      obtained from 3 * 10(-8) M to 4 * 10(-6) M and 2 * 10(-8) M to 5 * 10(-6) M, with
      R. S. D. were 1.6 % and 1.2 % for OLZ and QUT, respectively. The limit of
      detection (LOD) was 1 * 10(-8) M, while the limit of quantification (LOQ) was 3 *
      10(-8) M. CONCLUSION: The method was applied to the determination of investigated
      drugs in urine and serum samples and dosage forms.

PMID- 24312859
TI  - Effect of Phaleria macrocarpa on Sperm Characteristics in Adult Rats.
AB  - PURPOSE: The purpose of this study was to determine the effects of Phaleria
      macrocarpa (PM) on male fertility by assessing its effect on the sperm
      characteristics which included the sperm count, motility, viability and
      morphology. METHODS: Eighteen male rats were equally divided into three groups.
      Each group of rats was orally supplemented for 7 weeks either with PM aqueous
      extract (240 mg/kg), distilled water (0 mg/kg) or testosterone hormone,
      Andriol(r) TestocapsTM (4 mg/kg) respectively. On the last day of supplementation
      period, the rats were sacrificed and sperm was obtained from cauda epididymis via
      orchidectomy. The sperm count, motility, viability and morphology were
      determined. RESULTS: PM aqueous extract significantly increased (p<0.05) the
      percentage of sperm viability. However, there was no significant effect of PM on
      the percentage of both sperm motility and morphology. The mean of body weight
      declined significantly in rats supplemented with PM aqueous extract compared to
      control groups (p<0.05). CONCLUSION: The results showed that PM significantly
      increased sperm viability without changing the sperm motility and morphology.
      Hence, this study suggests that PM offers an alternative way to improve male
      fertility by improving the sperm quality.

PMID- 24312860
TI  - GABAB Receptor Blockade Prevents Antiepileptic Action of Ghrelin in the Rat
      Hippocampus.
AB  - PURPOSE: Ghrelin has been shown to have antiepileptic function. However, the
      underlying mechanisms by which, ghrelin exerts its antiepileptic effects are
      still unclear. In the present study; we investigated antiepileptic mechanism of
      ghrelin through GABAB receptors using CGP35348 (selective GABAB receptor
      antagonist). METHODS: Male Wistar rats' hippocampi were bilaterally microinjected
      with the single dose or 10-day ghrelin (0.3 nmol/ul/side). CGP35348, GABAB
      receptor antagonist, (12.5 ug/ul/side) or saline injected into the dorsal
      hippocampus 20 minutes before ghrelin administration. Thirty min after ghrelin
      microinjection, a single convulsive dose of pentylenetetrazole (PTZ) (50 mg/kg)
      was injected intraperitoneally (i.p). Afterwards, seizure duration and total
      seizure score (TSS) were assessed for 30 minutes in all animals. RESULTS: Our
      results demonstrated that acute and chronic intrahippocampal (i.h.) injection of
      ghrelin could significantly (p<0.001) attenuate the severity of seizures. Ghrelin
      0.3 nmol/ul/side decreased duration of seizure significantly both in acute
      (p<0.001) and chronic (p<0.01) injections. The ghrelin antiepileptic effect was
      completely antagonized by GABAB blockade. The suppression of both duration and
      TSS induced by ghrelin in hippocampus was significantly (p<0.001) blocked by
      CGP35348 in PTZ-induced seizures. CONCLUSION: In summary, our findings suggest
      that GABAB receptors may mediate the antiepileptic action of ghrelin in the
      hippocampus. Therefore, it is possible to speculate that ghrelin acts in the
      hippocampus to modulate seizures via GABA.

PMID- 24312861
TI  - In vivo assessment of antihyperglycemic and antioxidant activity from oil of
      seeds of brassica nigra in streptozotocin induced diabetic rats.
AB  - PURPOSE: This study was made to investigate the antihyperglycemic and antioxidant
      potential of oil of seeds of Brassica nigra (BNO) in streptozotocin -nicotinamide
      (STZ) induced type 2 diabetic rats. METHODS: BNO was orally administered to
      diabetic rats to study its effect in both acute and chronic antihyperglycemic
      study. The body weight, oral glucose tolerance test and biochemical parameters
      viz. glucose level, insulin level, liver glycogen content, glycosylated
      hemoglobin and antioxidant parameters were estimated for all treated groups and
      compared against diabetic control group. RESULTS: Administration of BNO at a dose
      500 mg/kg and 1000 mg/kg body weight p.o. to STZ diabetic rats showed reduction
      in blood glucose level from 335 mg/dl to 280 mg/dl at 4th h and from 330 mg/dl to
      265 mg/dl respectively which was found significant (p<0.01) as compared with
      diabetic control. BNO (500 mg/kg and 1000 mg/kg) and glibenclamide (0.6 mg/kg) in
      respective groups of diabetic animals administered for 28 days reduced the blood
      glucose level in streptozotocin-nicotinamide induced diabetic rats. There was
      significant increase in body weight, liver glycogen content, plasma insulin level
      and decrease in glycosylated hemoglobin in test groups as compared to control
      group. In vivo antioxidant studies on STZ-nicotinamide induced diabetic rat's
      revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH).
      CONCLUSION: Thus the results showed that the oil of seeds of Brassica nigra has
      significant antihyperglycemic and antioxidant activity.

PMID- 24312862
TI  - Thin layer chromatographic analysis of Beta-lactam antibiotics.
AB  - PURPOSE: The paper describes some thin layer chromatographic procedures that
      allow simple and rapid separation and identification of penicillins and
      cephalosporins from complex mixtures. METHODS: Using silicagel GF254 as
      stationary phase and selecting different mobile phases we succeeded in the
      separation of the studied beta-lactamins. Our aim was not only to develop a
      simple, rapid and efficient method for their separation but also the optimization
      of the analytical conditions. RESULTS: No system will separate all the beta
      lactams, but they could be identified when supplementary information is used from
      color reactions and/or by using additional chromatographic systems. CONCLUSIONS:
      The right combination of solvent system and detection method allows the
      identification of the studied penicillins and cephalosporins and can be
      successfully used in the preliminary analysis beta-lactam antibiotics.
      CONCLUSION: The right combination of solvent system and detection method allows
      the identification of the studied penicillins and cephalosporins and can be
      successfully used in the preliminary analysis beta-lactam antibiotics.

PMID- 24312863
TI  - Study of patient pain management after heart surgery.
AB  - PURPOSE: To investigate postoperative pain control and analgesic use after heart
      surgery. METHODS: 20 patients undergone heart surgery, randomly entered the
      study. Each patient was asked to score his pain intensity on visual analog scale
      (VAS) at four different occasions. RESULTS: 120 patients aged 59 year-old;
      including 81 male were enrolled in the study. 69.2% had coronary artery disease
      and 16.7% had heart-valve problem. Main types of surgeries were coronary artery
      bypass surgery (70.5%) and valve repairement (23%). Duration of ICU stay was
      4.78+/-2.7 days and duration of intubations was 17.38 +/- 36.46 hours. Pre
      surgery pain relief was administrated to 42% of the subjects and morphine and
      promethazine was the main pre-surgery analgesia medication. Post surgery
      analgesic included morphine (injection), petidine (injection) and NSAIDS (oral or
      rectal). According to VAS, mean pain level, 1 and 4 hours after extubation, and
      before and one hour after transferring to wards was 5.05+/-2.5, 4.09+/-2.0,
      3.52+/-1.8, 2.36+/-1.89, respectively. Although the level of pain reported was
      mostly moderate, 80% were reported satisfaction with their post-surgery pain
      management. CONCLUSION: A closer pain management control is needed for patients
      after heart surgery. Introduction of newer pain management techniques,
      medications and dosages could reduce the pain and suffering.

PMID- 24312864
TI  - Study on Phytochemical Composition, Antibacterial and Antioxidant Properties of
      Different Parts of Alstonia scholaris Linn.
AB  - PURPOSE: To evaluate phytochemical composition, antibacterial and antioxidant
      properties of methanolic extracts of different parts viz., leaves, follicles and
      latex of Indian devil tree (Alstonia scholaris Linn.) R. Br. METHODS:
      Antibacterial activities of the methanol extracts against Gram +ve (Bacillus
      subtilis and Staphylococcus aureus) and Gram -ve (Escherichia coli, Pseudomonas
      aeruginosa) bacteria were determined by well diffusion techniques. Aantioxidant
      profiles of methanol extracts were determined by 1,1-diphenyl-2-picryl-hydrazil
      (DPPH) free radical scavenging, superoxide anion radial scavenging and ferric
      thiocyanate reducing assays. RESULTS: Phytochemical composition revealed
      abundance of flavonoids (97.3 mg QE/g DW), proanthocynidins (99.3 mg CE/g DW) and
      phenolics (49.7 mgGAE/g DW) in the leaf extract. Extracts of follicles and latex
      had comparatively very content of phenolics, flavonoids and proanthocyanidins.
      However, in follicle extract level of proanthocyanidins was significantly higher
      (46.8 mg CE/gDW). Latex extract among others exhibited most potent antibacterial
      activity. All the extracts displayed strong DPPH free radical and superoxide
      anion scavenging activities, only leaf extract displayed powerful reducing and
      ferrous ion chelating activities. CONCLUSION: Study revealed significant
      antioxidant activities of A. scholaris leaf, follicles and latex extracts and
      potential antibacterial activity of latex extract.

PMID- 24312865
TI  - Rhizomes of Eremostachys laciniata: Isolation and Structure Elucidation of
      Chemical Constituents and a Clinical Trial on Inflammatory Diseases.
AB  - PURPOSE: The purpose of this study was the isolation and structure elucidation of
      chemical compounds from the rhizomes of Eremostachys laciniata (L) Bunge (EL), an
      Iranian traditional medicinal herb with a thick root and pale purple or white
      flowers as well as the clinical studies on the therapeutic efficacy and safety of
      topical application of the EL extract in the management of some inflammatory
      conditions, e.g., arthritis, rheumatoid arthritis and septic arthritis (Riter's
      syndrome). METHODS: The structures of the isolated compounds were elucidated
      unequivocally on the basis of one and two dimensional NMR, UV and HR-FABMS
      spectroscopic data analyses. A single-blinded randomized clinical trial was
      carried out with the extract of the rhizomes of E. laciniata (EL) to determine
      the efficacy and safety of the traditional uses of EL compared to that of
      piroxicam in treatment of inflammatory diseases, e.g., osteoarthritis, rheumatoid
      arthritis and Reiter's syndrome. RESULTS: Eleven iridoid glycosides, two
      phenylethanoids and two phytosterols were isolated and identified for the first
      time from the rhizomes of EL. After 14 days of treatment with the EL and
      piroxicam ointments, all groups showed significant improvements compared to the
      control groups. EL (5%) ointment induced better initial therapeutic response than
      piroxicam (5%) onitment. CONCLUSION: This clinical trial established that EL was
      suitable for topical applications as a safe and effective complementary therapy
      for inflammatory diseases.

PMID- 24312866
TI  - Influence of Foreign DNA Introduction and Periplasmic Expression of Recombinant
      Human Interleukin-2 on Hydrogen Peroxide Quantity and Catalase Activity in
      Escherichia coli.
AB  - PURPOSE: Oxidative stress is generated through imbalance between composing and
      decomposing of reactive oxygen species (ROS). This kind of stress was rarely
      discussed in connection with foreign protein production in Escherichia coli.
      Effect of cytoplasmic recombinant protein expression on Hydrogen peroxide
      concentration and catalase activity was previously reported. In comparison with
      cytoplasm, periplasmic space has different oxidative environment. Therefore, in
      present study we describe the effect of periplasmic expression of recombinant
      human interleukin-2 (hIL-2) on H2O2 concentration and catalase activity in
      Escherichia coli and their correlation with cell growth. METHODS: Having
      constructed pET2hIL2 vector, periplasmic expression of hIL-2 was confirmed. Then,
      H2O2 concentration and catalase activity were determined at various ODs. Wild
      type and empty vector transformed cells were used as negative controls. RESULTS:
      It was shown that H2O2 concentration in hIL-2 expressing cells was significantly
      higher than its concentration in wild type and empty vector transformed cells.
      Catalase activity and growth rate reduced significantly in hIL-2 expressing cells
      compared to empty vector transformed and wild type cells. Variation of H2O2
      concentration and catalase activity is intensive in periplasmic hIL-2 expressing
      cells than empty vector containing cells. Correlation between H2O2 concentration
      elevation and catalase activity reduction with cell growth depletion are also
      demonstrated. CONCLUSION: Periplasmic expression of recombinant hIL-2 elevates
      the host cell's hydrogen peroxide concentration possibly due to reduced catalase
      activity which has consequent suppressive effect on growth rate.

PMID- 24312867
TI  - Cytotoxic effects of alcoholic extract of dorema glabrum seed on cancerous cells
      viability.
AB  - PURPOSE: In the present study cytotoxic effects of the alcoholic extract of
      Dorema Glabrum seed on viability of WEHI-164 cells, mouse Fibrosarcoma cell line
      and L929 normal cells were compared with the cytotoxic effects of Taxol
      (anticancer and apoptosis inducer drug). METHODS: To find out the plant extract
      cytotoxic effects, MTT test and DNA fragmentation assay, the biochemical hallmark
      of apoptosis were performed on cultured and treated cells. RESULTS: According to
      the findings the alcoholic extract of Dorema Glabrum seed can alter cells
      morphology and because of chromatin condensation and other changes they shrink
      and take a spherical shape, and lose their attachment too. So the plant extract
      inhibits cell growth albeit in a time and dose dependent manner and results in
      degradation of chromosomal DNA. CONCLUSION: Our data well established the anti
      proliferative effect of methanolic extract of Dorema Glabrum seed and clearly
      showed that the plant extract can induce apoptosis and not necrosis in vitro, but
      the mechanism of its activities remained unknown. These results demonstrated that
      Dorema Glabrum seed might be a novel and attractive therapeutic candidate for
      tumor treatment in clinical practices.

PMID- 24312868
TI  - A Novel Approach using Hydrotropic Solubalization Technique for Quantitative
      Estimation of Entacapone in Bulk Drug and Dosage Form.
AB  - PURPOSE: Analysis of drug utilized the organic solvent which are costlier, toxic
      and causing environment pollution. Hydrotropic solution may be a proper choice to
      preclude the use of organic solvents so that a simple, accurate, novel, safe and
      precise method has been developed for estimation of poorly water soluble drug
      Entacapone (Water Solubility-7.97e-(02) g/l). METHODS: Solubility of entacapone
      is increased by using 8M Urea as hydrotropic agent. There was more than 67 fold
      solubility enhanced in hydrotropic solution as compare with distilled water. The
      entacapone (ENT) shows the maximum absorbance at 378 nm. At this wavelength
      hydrotropic agent and other tablet excipients do not shows any significant
      interference in the spectrophotometric assay. RESULTS: The developed method was
      found to be linear in the range of 4-20 MUg/ml with correlation coefficient
      (r(2)) of 0.9998. The mean percent label claims of tablets of ENT in tablet
      dosage form estimated by the proposed method were found to be 99.17+/-0.63. The
      developed methods were validated according to ICH guidelines and values of
      accuracy, precision and other statistical analysis were found to be in good
      accordance with the prescribed values. CONCLUSION: As hydrotropic agent used in
      the proposed method so this method is Ecofriendly and it can be used in routine
      quantitative analysis of drug in bulk drug and dosage form in industries.

PMID- 24312869
TI  - Composition and antibacterial activity of heracleum transcaucasicum and heracleum
      anisactis aerial parts essential oil.
AB  - PURPOSE: Two plant essential oils (EOs), including those from Heracleum
      transcaucasicum and Heracleum anisactiss (Umbeliferae) were studied to detect the
      chemical constituents and evaluated for their antibacterial activities against
      Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and
      Pseudomonas aeruginosa. METHODS: The EOs of H. transcaucasicum and H.anisactis
      (Apiacae) were obtained by hydrodistillation from aerial parts of the plants. The
      chemical analyses of the EOs were performed by GC/Mass spectrometry (GC/MS).
      Myristicin was found to be the principal constituent in both EOs. The
      susceptibility tests of EOs were performed by agar disc diffusion technique
      against Gram-positive and Gram-negative bacterial strains. RESULTS: Eight
      components comprising 99.97% of the total essential oil of H. transcaucasicum and
      a total of three compounds accounting for 98.5% of the total oil composition of
      aerial parts of H. anisactis were identified, of which myristicin was the main
      compound in both EOs. The EOs of H. transcaucasicum and H. anisactis showed weak
      antibacterial property against Gram-positive strains of Staphylococcus aureus and
      Staphylococcus epidermidis with no measurable effect on Escherichia coli and
      Pseudomonas aeruginosa. CONCLUSION: Our GC-MS study revealed myristicin to be the
      major constituent of H. transcaucasicum and H.anisactis aerial parts. In spite of
      all the information available on the antibacterial properties of plants essential
      oils, we were not able to find significant antibacterial activity for both EOs.

PMID- 24312870
TI  - Thermal analysis of some antidiabetic pharmaceutical compounds.
AB  - PURPOSE: Thermal behavior of some antidiabetic drugs such as pioglitazone
      hydrochloride (PTZ), rosiglitazone maleate (RGZ), glibenclamide (GBD) and
      glimepiride (GMP) has been studied. METHODS: Thermogravimetric analysis (TGA),
      derivative thermogravimetry (DTG) and differential thermal analysis (DTA)
      techniques were used to study the thermal behavior of the drugs under
      investigation. RESULTS: Thermal analysis technique was used to obtain quality
      control parameters such as melting point 193.13  degrees C, 122.42  degrees C,
      173.75  degrees C and 208  degrees C for PTZ, RGZ, GBD and GMP, respectively. The
      values of melting point of gave satisfactory results in comparison to that
      obtained by using the official method. Non-isothermal methods were employed to
      determine the activation energy values of the first stage of thermal
      decomposition. Comparison of the activation energy values suggests the following
      sequence of thermal stability: GMP > GBD > RGZ > PTZ. CONCLUSION: The results
      obtained are useful for the identification of these compounds and permitted
      interpretations concerning their thermal decomposition. Thermal stability of
      pharmaceutical compounds can be studied and compared by using thermal analysis
      techniques.

PMID- 24312871
TI  - Preparation, physicochemical characterization and performance evaluation of gold
      nanoparticles in radiotherapy.
AB  - PURPOSE: The aim of the present study was preparation, physicochemical
      characterization and performance evaluation of gold nanoparticles (GNPs) in
      radiotherapy. Another objective was the investigation of anti-bacterial efficacy
      of gold nanoparticle against E. coli clinical strains. METHODS: Gold
      nanoparticles prepared by controlled reduction of an aqueous HAuCl4 solution
      using Tri sodium citrate. Particle size analysis and Transmission electron
      microscopy were used for physicochemical characterization. Polymer gel dosimetry
      was used for evaluation of the enhancement of absorbed dose. Diffusion method in
      agar media was used for investigation of anti-bacterial effect. RESULTS: Gold
      nanoparticles synthesized in size range from 57 nm to 346 nm by planning
      different formulation. Gold nanoparticle in 57 nm size increased radiation dose
      effectiveness with the magnitude of about 21 %. At the concentration of 400 ppm,
      Nano gold exhibited significant anti-bacterial effect against E. coli clinical
      strains. CONCLUSION: It is concluded that gold nanoparticles can be applied as
      dose enhancer in radiotherapy. The Investigation of anti-bacterial efficacy
      showed that gold nanoparticle had significant effect against E. coli clinical
      strains.

PMID- 24312872
TI  - Characterization of Non-Terpenoids in Marrubium crassidens Boiss. Essential Oil.
AB  - PURPOSE: Marrubium crassidens, a plant belonging to the family Lamiaceae, was
      studied for its volatile components present in the aerial parts of the plant
      during the flowering stage. METHODS: The essential oil of the plant obtained
      through hydrodistillation of the dried plant material was assessed for its
      chemical composition by GC/MS and GC-FID analyses. RESULTS: Twenty-five compounds
      were identified, which constituted 94.3% of the total oil composition. The major
      components were identified as, m-tolualdehyde (23.3%), acetophenone (15.8%),
      nonacosane (13.1%), docosane (7.2%), o-tolualdehyde (4.1%), beta-caryophyllene
      (3.8%) and caryophyllene oxide (3.4%). Non-terpenoids with 75.7% were the most
      abundant components of the essential oil. CONCLUSION: Overall, M. crassidens
      essential oil revealed to include rather higher proportions of non-terpenoid
      compounds compared with other species of genus Marrubium.

PMID- 24312873
TI  - Mesenchymal stem cells: new aspect in cell-based regenerative therapy.
AB  - MSCs are multipotent progenitors which reside in bone marrow. They support
      hematopoietic stem cells homing, self renewal and differentiation in bone marrow.
      They can also differentiate into osteoblasts, adipocytes, chondrocytes, myocyates
      and many other tissues. In vivo, when trauma happens, MSCs operate cell renewal
      and migrate to the damaged tissues to regenerate that injury. In vitro, MSCs are
      able to proliferate and differentiate to a variety of cell lineages. This makes
      them a very hopeful tool for cell-based regenerative therapy for large bone
      defects, maxillofacial skeletal reconstruction, cardiovascular and spinal cord
      injury and so many other defects. The most important characteristic that make
      MSCs an excellent tool for cell replacement is their ability to escape from
      immune rejection. For therapeutic purposes they usually isolated from human bone
      marrow or fat and they should proliferate in order to reach an adequate number
      for implantation. Conventionally DMEM medium supplemented with 10% FBS is used
      for their expansion, but currently autologous platelet rich products are replaced
      FBS. Platelet granules contain so many growth factors that can support MSCs
      proliferation. 

PMID- 24312874
TI  - Dampening of Serotonergic System through 5HT1A Receptors is a Promising Target
      for Treatment of Levodopa Induced Motor Problems.
AB  - During long-term treatment with Levodopa, majority of patients with Parkinson's
      disease experience some abnormal motor problems including of Levodopa induced
      dyskinesia (LID) and wearing off. Incredible evidences suggest that serotonergic
      neurons compensate some functions of lost dopaminergic neurons in Parkinson's
      disease especially in advanced disease stages. Therefore, it has been postulated
      that serotonergic neurons are the major source for development of these unwanted
      effects. 5HT1A receptors are located on the serotonergic neurons and are involved
      in regulation of normal motor functions. With respect to the role of serotonergic
      projection in Parkinson's disease and importance of 5HT1A receptors in motor
      activity it seems that inactivation of these neurons by stimulation of 5HT1A
      receptors could provide benefits in treatment of Levodopa induced motor
      impairments. 

PMID- 24312875
TI  - HLA-G Expression Pattern: Reliable Assessment for Pregnancy Outcome Prediction.
AB  - Because mothers and fathers are more or less dissimilar at multiple HLA loci,
      mother considers her fetus as a semi-allograft. Mother's immune system may
      recognize paternal HLA as foreign antigen and may develop anti-paternal HLA
      antibodies and cytotoxic T lymphocyte. There are some mechanisms that modulate
      maternal immune responses during pregnancy, in order to make uterus an immune
      privileged site. This immunosuppression is believed to be mediated, at least
      partly, by HLA-G, non-classical class I human leukocyte antigen (HLA) molecule
      that is strongly expressed in cytotrophoblast and placenta. The major HLA-G
      function is its ability to inhibit T and B lymphocytes, NK cells and antigen
      presenting cells (APC).Since HLA-G is expressed strongly at the maternofetal
      interface and has an essential role in immunosuppression, HLA-G polymorphism and
      altered expression of HLA-G seems to be associated with some complications of
      pregnancy, such as pre-eclampsia, recurrent misscariage and failure in IVF.This
      perspective discusses recent findings about HLA-G genetics, function, expression
      and polymorphism; and focus on HLA-G role in the etiology of recurrent
      miscarriage. 

PMID- 24312876
TI  - Development and Validation of UV-Visible Spectrophotometric Method for
      Simultaneous Determination of Eperisone and Paracetamol in Solid Dosage Form.
AB  - PURPOSE: Eperisone Hydrochloride (EPE) is a potent new generation antispasmodic
      drug which is used in the treatment of moderate to severe pain in combination
      with Paracetamol (PAR). Both drugs are available in tablet dosage form in
      combination with a dose of 50 mg for EPE and 325 mg PAR respectively. METHODS:
      The method is based upon Q-absorption ratio method for the simultaneous
      determination of the EPE and PAR. Absorption ratio method is used for the ratio
      of the absorption at two selected wavelength one of which is the iso-absorptive
      point and other being the lambdamax of one of the two components. EPE and PAR
      shows their iso-absorptive point at 260 nm in methanol, the second wavelength
      used is 249 nm which is the lambdamax of PAR in methanol. RESULTS: The linearity
      was obtained in the concentration range of 5-25 MUg/mL for EPE and 2-10 MUg/mL
      for PAR. The proposed method was effectively applied to tablet dosage form for
      estimation of both drugs. The accuracy and reproducibility results are close to
      100% with 2% RSD. RESULTS of the analysis were validated statistically and found
      to be satisfactory. The results of proposed method have been validated as per ICH
      guidelines. CONCLUSION: A simple, precise and economical spectrophotometric
      method has been developed for the estimation of EPE and PAR in pharmaceutical
      formulation.

PMID- 24312877
TI  - In vitro Cytotoxic Activity of Four Plants Used in Persian Traditional Medicine.
AB  - PURPOSE: The aim of this study was to investigate in vitro cytotoxic activity of
      four methanolic crude plant extracts against panel cell lines. METHODS:
      Methanolic extracts were tested for their possible antitumor activity and
      cytotoxicity using the 3-(4,5-dimetylthiazol-2-yl)-2,5- diphenyltetrazolium
      bromide (MTT) assay on six cancer cell lines; non-Hodgkin's B-cell lymphoma
      (Raji), human leukemic monocyte lymphoma (U937), human acute myelocytic leukemia
      (KG-1A), human breast carcinoma (MCF-7 cells), human Prostate Cancer (PC3) and
      mouse fibrosarcoma (WEHI-164) cell lines and one normal cell line; Human
      Umbilical Vein Endothelial Cells (HUVEC). RESULTS: All species showed dose
      dependent inhibition of cell proliferation. IC50 values ranging from 25.66+/-1.2
      to 205.11+/-1.3 MUg/ml. The highest cytotoxic activity Chelidonium majus L>
      Ferulago Angulata DC> Echinophora platyloba DC> Salvia officinalis L,
      respectively. CONCLUSION: all extracts demonstrate promising cytotoxicity
      activity as a natural resource for future bio-guided fractionation and isolation
      of potential antitumor agents.

PMID- 24312878
TI  - Antinociceptive activity and effect of methanol extracts of three salvia spp. On
      withdrawal syndrome in mice.
AB  - PURPOSE: There are several reports about effects of Salvia spp. on CNS. The
      present experiment is undertaken to study effect of S. limbata, S. hypoleuca and
      S. macrosiphon on withdrawal syndrome in mice. METHODS: Antinociceptive
      activities of aerial parts of Salvia spp. is investigated using hot plate method.
      In addition, the effect of its aerial parts on morphine dependence is
      investigated in mice. After induction of morphine dependency, different
      concentrations of plant extract are injected. To assess morphine withdrawal,
      naloxone (5 mg kg-1, i.p.) are injected into mice on the 5th day. Withdrawal
      syndrome is assessed by placing each mouse in a glass box 30 cm in height and
      recording the incidence of escape jumps for 60 minutes. RESULTS: A decrease in
      incidence of escape jumps is observed in morphine dependence mice. S. limbata and
      S. hypoleuca extracts produced a statistically significant inhibition of pain
      induced by hot plate latency at (500, 1000 and 1500 mg kg-1) i.p. A significant
      increase in pain threshold is observed after 30 and 60 minutes (p < 0.001). The
      activity was comparable to that of morphine (30 mg kg-1, i.p., p > 0.05). The
      antinociceptive activity increased up to 60 minutes. CONCLUSION: S. limbataand S.
      hypolecuca extracts produced statistically significant inhibition of pain and
      development of morphine dependence in mice.

PMID- 24312880
TI  - Investigation of Phenolic Profiles, Cytotoxic Potential and Phytochemical
      Screening of Different Extracts of Drynaria quercifolia J. Smith (Leaves).
AB  - PURPOSE: The present study is aimed to evaluate phenolic profiles, cytotoxic
      activity and phytochemical screening of different extracts of Drynaria
      quercifolia leaves. METHODS: The dried and powder leaves were extracted with
      methanol at room temperature and the concentrated methanolic extract was
      fractionated by the modified Kupchan partitioning method to provide pet-ether,
      carbon tetrachloride, chloroform and aqueous soluble fractions. Phenolic profiles
      were determined by using Folin-Ciocalteau reagent, which results were expressed
      in gallic acid equivalent (mg of GAE/g of sample). Phytochemical properties of
      different extractives of plant materials were tested by the method of Trease and
      Evans. Brine shrimp lethality bioassay was used to investigate the cytotoxic
      potential of D. quercifolia. RESULTS: The phytochemical screening revealed the
      potent source of different phytochemical constituents on different extractives
      including alkaloid, glycosides, tannin, saponins, proteins and amino acids,
      flavonoids, triterpenes, phenols, phytosterols and carbohydrate. In the
      determination of phenolic profiles, different extractives showed a significant
      content of phenolic compounds ranging from 103.43 -132.23 mg of GAE/g of
      extractive. Compared to vincristine sulfate different extractives of plant
      materials demonstrated moderate cytotoxic potential (having LC50 of 12.45 MUg/ml,
      13.02 MUg/ml 15.83 MUg/ml, 14.95 MUg/ml and 7.612 MUg/ml, respectively).
      CONCLUSION: It is concluded from this study that D. quercifolia is an excellent
      source of phenolic content and phytoconstitutes as well as possesses moderate
      cytotoxic activity.

PMID- 24312879
TI  - Evaluation of STAT5A Gene Expression in Aflatoxin B1 Treated Bovine Mammary
      Epithelial Cells.
AB  - PURPOSE: Aflatoxin B1 (AFB1) is a potent mycotoxin which has been produced by
      fungi such as Aspergillus flavus and Aspergillus parasiticus as secondary
      metabolites due to their growth on food stuffs and induces hepatocellular
      carcinoma in many animal species, including humans. In the present study, the
      effect of AFB1 on STAT5A gene expression was investigated in bovine mammary
      epithelial cells using real time RT-PCR. METHODS: Bovine mammary epithelial cells
      were seeded in a 24-well culture plate for three-dimensional (3D) culture in
      Matrigel matrix. After 21 days of 3D culture and reaching the required number of
      cells, cells were treated with AFB1 and incubated for 8 h. For real time PCR
      reaction, total RNA from the cultured and treated cells was extracted and used
      for complementary DNA synthesis. RESULTS: The expression of STAT5A gene was
      significantly down regulated by AFB1 in dose- dependent manner and led to the
      reduction of proliferation and differentiation of epithelial cells, which has
      direct effect in milk protein quantity and quality. CONCLUSION: According to the
      results, it seems that down regulation of STAT5A gene in AFB1-treated cells maybe
      due to DNA damage induced by AFB1 in bovine mammary epithelial cells.

PMID- 24312881
TI  - Validated spectrophotometric quantification of aripiprazole in pharmaceutical
      formulations by using multivariate technique.
AB  - PURPOSE: An accurate and precise UV spectrophotometric method with multivariate
      calibration technique for the determination of aripiprazole in pharmaceutical
      formulations has been described. METHODS: This technique is based on the use of
      the linear regression equations by using the relationship between concentration
      and absorbance at five different wavelengths. The aripiprazole shows absorption
      maxima at 255 nm and obeyed Beer's law in the range of 5-30 ug/mL. RESULTS: The
      results were treated statistically and were found highly accurate, precise and
      reproducible. This statistical approach gives optimum results for the eliminating
      fluctuations coming from instrumental or experimental conditions. CONCLUSION: It
      was concluded that the proposed method is simple, easy to apply, economical and
      could be used as an alternative to the existing spectrophotometric and non
      spectrophotometric methods for the routine analysis of aripiprazole in
      pharmaceutical formulations.

PMID- 24312882
TI  - Construction of Yeast Recombinant Expression Vector Containing Human Epidermal
      Growth Factor (hEGF).
AB  - PURPOSE: The objective of this study was construction of recombinant hEGF-pPIC9
      which may be used for expression of recombinant hEGF in following studies.
      METHODS: EGF cDNA was purchased from Genecopoeia Company and used for PCR
      amplification. Prior to ligation, the PCR product and pPIC9 vector was digested
      with EcoRI and XhoI and ligated in pPIC9 vector and subjected to colony PCR
      screening and sequencing analysis. RESULTS: PCR amplification of EGF cDNA using
      recombinant hEGF-pPIC9 vector as template was concluded in amplification of 197bp
      fragment. Construction of recombinant hEGF-pPIC9 of EGf gene was verified by PCR
      and sequencing. CONCLUSION: Construction of Recombinant hEGF-pPIC9 was the
      primary stage for production and expression of EFG in the future study.

PMID- 24312883
TI  - Antiurolithiatic activity of gokhsuradi churan, an ayurvedic formulation by in
      vitro method.
AB  - PURPOSE: Gokhsuradi churna is an ayurvedic formulation, was investigate for
      antiurolithiatic activity. METHODS: Calcium oxalate crystallization was induced
      by the addition of 0.01M sodium oxalate solutions in synthetic urine and
      nucleation method. RESULTS: The effect of Gokhsuradi Churna exhibited a
      concentration dependent inhibition of on calcium oxalate crystallization and
      nucleation. CONCLUSION: The present studies suggest that Gokhsuradi churna has a
      potential inhibition of calcium oxalate crystallization exhibited and nucleation.
      Gokhsuradi Churna showed potent antiurolethiatic activity.

PMID- 24312884
TI  - Taking the 'Risk' out of risk-based monitoring.

PMID- 24312885
TI  - Causality assessment: A casualty of compensation?
AB  - Recent Indian rule on compensation for any injury or death of the subject in a
      clinical trial, has generated a lot of discussion on its impact on clinical
      trials in India. The legal process in the compensation rule is based on the
      causality assessment. However, it ignores the scientific basis of causality
      assessment. This could have far reaching consequences on (1) science of causality
      assessment and (2) safety assessment of a new drug under clinical development.
      There is a need to bring clarity on causality assessment process within the
      compensation rules to balance the ethical need of human subject protection and
      the scientific requirements of safety assessment. 

PMID- 24312886
TI  - Injury and death in clinical trials and compensation: Rule 122 DAB.
AB  - Three amendments to the drugs and cosmetics rules were published in quick
      succession in 2013. These addressed the issues of compensation of injury and
      death in clinical trials in addition to the role and registration of Ethics
      Committees. Of the three, the first and the third make an impact on the clinical
      research activities in India. The second amendment has codified the conduct of
      clinical trials, putting together rules, which appeared in different sections of
      Schedule Y. The first amendment deals with the compensation for injuries and
      deaths taking place during clinical trials while the third deals with
      registration of Ethics Committees. Despite the long delay in the issue of
      compensation rules, there appears significant room for improvement. The most
      problematic are conditions of injury and death in which compensation has to be
      paid. When compared with other countries, the Indian rules seem unduly harsh on
      sponsors and are at significant variance with those in UK. The rules are very
      generous toward subjects and compensation is likely to become an alternative to
      insurance in terminally ill subjects. The implementation of these rules will make
      clinical trials in India more expensive and hurt the industry that is already
      struggling through other handicaps. There is an urgent need to make the the
      environment more industry friendly to attract more clinical work. 

PMID- 24312887
TI  - An evaluation of knowledge, attitude and practice of Indian pharmacists towards
      adverse drug reaction reporting: A pilot study.
AB  - BACKGROUND: Pharmacovigilance is a useful to assure the safety of medicines and
      protect consumers from their harmful effects. Healthcare professionals should
      consider Adverse Drug Reaction (ADR) reporting as part of their professional
      obligation and participate in the existent pharmacovigilance programs in their
      countries. In India, the National PV Program was re-launched in July 2010.
      OBJECTIVES: This survey was conducted in order to assess the knowledge, attitude
      and practice of Indian pharmacists with the aim of exploring the pharmacists'
      participation in ADR reporting system, identifying the reasons of under reporting
      and determining the steps that could be adopted to increase reporting rates.
      MATERIALS AND METHODS: A cross-sectional survey was carried out among the
      pharmacists in India using a pretested questionnaire with 33 questions (10
      questions on knowledge, 6 on attitude, 7 on practice, 7 on future of ADR
      reporting in India and 3 on benefits of reporting ADRs.). The study was
      conducted, over a period of 3 months from May 2012 to July 2012. RESULTS: Out of
      the 600 participants to whom the survey was administered, a total of 400 were
      filled. The response rate of the survey was 67%. 95% responders were
      knowledgeable about ADRs. 90% participants had a positive attitude towards making
      ADRs reporting mandatory for practicing pharmacists. 87.5% participants were
      interested in participating in the National Pharmacovigilance program, in India.
      47.5% respondents had observed ADRs in their practice, and 37% had reported it to
      the national pharmacovigilance center. 92% pharmacists believed reporting ADRs
      immensely helped in providing quality care to patients. CONCLUSION: The Indian
      pharmacists have poor knowledge, attitude, and practice (KAP) towards ADR
      reporting and pharmacovigilance. Pharmacists with higher qualifications such as
      the pharmacists with a PharmD have better KAP. With additional training on
      Pharmacovigilance, the Indian Pharmacists working in different sectors can become
      part of ADR reporting system.

PMID- 24312888
TI  - Feasibility study of clinical trial for breast cancer and lung cancer at Indian
      sites.
AB  - OBJECTIVE: The objective of this study was to conduct feasibility study of phase
      III breast and lung cancer clinical trials in India. MATERIALS AND METHODS: Study
      synopsis and feasibility questionnaire were mailed to 300 oncologists for each
      indication. Criteria of selection were enrolment of >=2 patients per month,
      frequency of Ethics Committee (EC) meeting <=4 weeks, dropout rate <20%, adequacy
      of infrastructure and training of site in good clinical practice (GCP).
      Descriptive analyses of the data were performed. RESULTS: For both indications,
      50/300 (16.7%) sites responded. The median number of patients seen by a site per
      month for breast and lung cancer was 20 (range 0-300) and 10 (range 0-75),
      respectively. Median number of eligible patients was 4 (range 0-20) and 3 (range
      0-15) per month, for breast and lung cancer respectively. The frequency of EC
      meeting was <=4 weeks at 36-56% of sites. All sites were trained in GCP and had
      adequate infrastructure to conduct the clinical trial. For breast cancer 22 (44%)
      sites (public 14 [28%]; private 8 [16%)]), and for lung cancer 18 (36%) sites
      (public 15 [30%], private: 3 [6%]) met the criteria of selection. CONCLUSION:
      Preliminary feasibility study would require for confirmation of the important
      feasibility criteria by in depth discussion during the personal visit to the
      potential sites.

PMID- 24312889
TI  - Early outcome of second line antiretroviral therapy in treatment-experienced
      human immunodeficiency virus positive patients.
AB  - PURPOSE AND AIM: Multi-drug resistance in treatment-experienced human immune
      deficiency virus (HIV) patients has been a major cause to first line
      antiretroviral therapy (ART) failure, necessitating a switch to second line
      therapy. In India, the second line treatment program is still relatively new with
      little experience and unclear outcomes. It is therefore, critical to assess the
      clinical, virological and immunological effectiveness and treatment outcome over
      the 1(st) year of follow-up in the patients' switched to the second line ART at
      public sector tertiary care center. MATERIALS AND METHODS: A prospective,
      observational study was carried out on HIV positive patients switched on second
      line ART from January 2010 to December 2010 at ART Centre, Civil Hospital,
      Ahmedabad. Demographic details, symptoms, adverse drug reactions (ADRs), second
      line ART regimens, CD4 count, and plasma viral load (PVL) were recorded in a case
      record form. Patients were followed-up monthly for 12 months. The data was
      analyzed by t-test, z-test, and Fisher-exact test. RESULTS: Out of 126 patients,
      82 received regimen V [zidovudine (ZDV) + lamivudine (3TC) + tenofovir (TDF) +
      boosted lopinavir (LPV/r)] and 44 received regimen Va [3TC + TDF + LPV/r]. A
      significant (P < 0.0001) increase in mean body weight and marked reduction in
      number of patients (7) categorized as WHO stage III/IV was observed at 12 months
      of second line ART. Moreover, a significant immune reconstitution with increase
      in mean CD4 count and viral suppression (PVL < 400 copies/ml) in 103 (82%)
      patients (P < 0.0001) was also observed. A total of 83 ADRs were observed in 69
      (55%) patients, the most common being dyslipidemia (57) followed by anemia (9).
      CONCLUSION: Early treatment outcome with second line ART was good with 82%
      success rate in treatment experienced HIV patients. Dyslipidemia and anemia were
      the common ADRs observed.

PMID- 24312890
TI  - A data-driven approach to quality risk management.
AB  - AIM: An effective clinical trial strategy to ensure patient safety as well as
      trial quality and efficiency involves an integrated approach, including
      prospective identification of risk factors, mitigation of the risks through
      proper study design and execution, and assessment of quality metrics in real
      time. Such an integrated quality management plan may also be enhanced by using
      data-driven techniques to identify risk factors that are most relevant in
      predicting quality issues associated with a trial. In this paper, we illustrate
      such an approach using data collected from actual clinical trials. MATERIALS AND
      METHODS: Several statistical methods were employed, including the Wilcoxon rank
      sum test and logistic regression, to identify the presence of association between
      risk factors and the occurrence of quality issues, applied to data on quality of
      clinical trials sponsored by Pfizer. RESULTS: ONLY A SUBSET OF THE RISK FACTORS
      HAD A SIGNIFICANT ASSOCIATION WITH QUALITY ISSUES, AND INCLUDED: Whether study
      used Placebo, whether an agent was a biologic, unusual packaging label, complex
      dosing, and over 25 planned procedures. CONCLUSION: Proper implementation of the
      strategy can help to optimize resource utilization without compromising trial
      integrity and patient safety.

PMID- 24312891
TI  - Practical solutions to challenges in research ethics proceedings of Bangalore
      conference.
AB  - On November 3(rd) and 4(th), 2012, Manipal Hospital, Bangalore and Association
      for the Accreditation of Human Research Protection Programs co-hosted a regional
      conference titled "Practical Solutions to Challenges in Research Ethics." This
      paper is a synthesis of the major themes of the conference. The authors discuss
      the current state of the clinical research in India today, need to focus on human
      research protection programs rather than Ethics Committees or institutional
      review boards, the factors that influence high-quality research and some
      practical solutions to improving the quality of research and the protection of
      research participants. 

PMID- 24312892
TI  - Causality assessment: A brief insight into practices in pharmaceutical industry.
AB  - Healthcare industry is flooded with multitude of drugs, and the list is
      increasing day by day. Consumption of medications has enormously increased due to
      life style changes, having safer drugs is the need of the hour. Regulators and
      other authorities to have a check have put in stringent regulations and
      pharmacovigilance system in place. Eventhough there has been increase in adverse
      drug reactions (ADR) reporting in the last decade, causality assessment has been
      the greater challenge for academicians and even industry. Causality is crucial
      for risk benefit assessment, particularly when it involves post marketing safety
      signals. Pharmaceutical companies have put in efforts to have a standardized
      approach for causality assessment. This article will provide some insight into
      the approaches for causality assessment from a pharma industry perspective. 

PMID- 24312893
TI  - Indian regulatory update 2013.

PMID- 24312894
TI  - Transparency in recruiting patients for clinical trials.

PMID- 24312895
TI  - Indian Medical Research: Encouraging trends.

PMID- 24312896
TI  - Combinatorial Resistance: The Best Defense is a Good Offense.

PMID- 24312897
TI  - Potential applications of imaging and image-guided radiotherapy for brain
      metastases and glioblastoma to improve patient quality of life.
AB  - Treatment of glioblastoma multiforme (GBM) and brain metastasis remains a
      challenge because of the poor survival and the potential for brain damage
      following radiation. Despite concurrent chemotherapy and radiation dose
      escalation, local recurrence remains the predominant pattern of failure in GBM
      most likely secondary to repopulation of cancer stem cells. Even though
      radiotherapy is highly effective for local control of radio-resistant tumors such
      as melanoma and renal cell cancer, systemic disease progression is the cause of
      death in most patients with brain metastasis. Preservation of quality of life
      (QOL) of cancer survivors is the main issue for patients with brain metastasis.
      Image-guided radiotherapy (IGRT) by virtue of precise radiation dose delivery may
      reduce treatment time of patients with GBM without excessive toxicity and
      potentially improve neurocognitive function with preservation of local control in
      patients with brain metastasis. Future prospective trials for primary brain
      tumors or brain metastasis should include IGRT to assess its efficacy to improve
      patient QOL. 

PMID- 24312898
TI  - Over-Expression of the LH Receptor Increases Distant Metastases in an Endometrial
      Cancer Mouse Model.
AB  - OBJECTIVE: The aim of the present study was to define the role of luteinizing
      hormone receptor (LH-R) expression in endometrial cancer (EC), using preclinical
      mouse models, to further transfer these data to the clinical setting. MATERIALS
      AND METHODS: The role of LH-R over-expression was studied using EC cells (Hec1A,
      e.g., cells with low endogenous LH-R expression) transfected with the LH-R (Hec1A
      LH-R). In vitro cell proliferation was measured through the WST-1 assay, whereas
      cell invasion was measured trough the matrigel assay. The effects of LH-R over
      expression in vivo were analyzed in an appropriately developed preclinical mouse
      model of EC, which mimicked postmenopausal conditions. The model consisted in an
      orthotopic xenograft of Hec1A cells into immunodeficient mice treated daily with
      recombinant LH, to assure high levels of LH. RESULTS: In vitro data indicated
      that LH-R over-expression increased Hec1A invasiveness. In vivo results showed
      that tumors arising from Hec1A-LH-R cells injection displayed a higher local
      invasion and a higher number of distant metastases, mainly in the lung, compared
      to tumors obtained from the injection of Hec1A cells. LH withdrawal strongly
      inhibited local and distant metastatic spread of tumors, especially those arising
      from Hec1A-LH-R cells. CONCLUSION: The over-expression of the LH-R increases the
      ability of EC cells to undergo local invasion and metastatic spread. This occurs
      in the presence of high LH serum concentrations.

PMID- 24312899
TI  - More than meets the eye: understanding Trypanosoma brucei morphology in the
      tsetse.
AB  - T. brucei, the causative parasite for African trypanosomiasis, faces an
      interesting dilemma in its life cycle. It has to successfully complete its
      infection cycle in the tsetse vector to be able to infect other vertebrate hosts.
      T. brucei has to undergo multiple morphological changes as it invades the
      alimentary canal of the tsetse to finally achieve infectivity in the salivary
      glands. In this review, we attempt to elucidate how these morphological changes
      are possible for a parasite that has evolved a highly robust cell structure to
      survive the chemically and physically diverse environments it finds itself in. To
      achieve this, we juxtaposed the experimental evidence that has been collected
      from T. brucei forms that are cultured in vitro with the observations that have
      been carried out on tsetse-infective forms in vivo. Although the accumulated
      knowledge on T. brucei biology is by no means trivial, several outstanding
      questions remain for how the parasite mechanistically changes its morphology as
      it traverses the tsetse and how those changes are triggered. However, we conclude
      that with recent breakthroughs allowing for the replication of the tsetse
      infection process of T. brucei in vitro, these outstanding questions can finally
      be addressed. 

PMID- 24312901
TI  - The exoribonuclease Polynucleotide Phosphorylase influences the virulence and
      stress responses of yersiniae and many other pathogens.
AB  - Microbes are incessantly challenged by both biotic and abiotic stressors
      threatening their existence. Therefore, bacterial pathogens must possess
      mechanisms to successfully subvert host immune defenses as well as overcome the
      stress associated with host-cell encounters. To achieve this, bacterial pathogens
      typically experience a genetic re-programming whereby anti-host/stress factors
      become expressed and eventually translated into effector proteins. In that vein,
      the bacterial host-cell induced stress-response is similar to any other abiotic
      stress to which bacteria respond by up-regulating specific stress-responsive
      genes. Following the stress encounter, bacteria must degrade unnecessary stress
      responsive transcripts through RNA decay mechanisms. The three pathogenic
      yersiniae (Yersinia pestis, Y. pseudo-tuberculosis, and Y. enterocolitica) are
      all psychrotropic bacteria capable of growth at 4 degrees C; however, cold growth
      is dependent on the presence of an exoribonuclease, polynucleotide phosphorylase
      (PNPase). PNPase has also been implicated as a virulence factor in several
      notable pathogens including the salmonellae, Helicobacter pylori, and the
      yersiniae [where it typically influences the type three secretion system (TTSS)].
      Further, PNPase has been shown to associate with ribonuclease E
      (endoribonuclease), RhlB (RNA helicase), and enolase (glycolytic enzyme) in
      several Gram-negative bacteria forming a large, multi-protein complex known as
      the RNA degradosome. This review will highlight studies demonstrating the
      influence of PNPase on the virulence potentials and stress responses of various
      bacterial pathogens as well as focusing on the degradosome-dependent and 
      independent roles played by PNPase in yersiniae stress responses. 

PMID- 24312902
TI  - Defining the interorgan communication network: systemic coordination of
      organismal cellular processes under homeostasis and localized stress.

PMID- 24312903
TI  - Examining the tsetse teneral phenomenon and permissiveness to trypanosome
      infection.
AB  - Tsetse flies are the most important vectors of African trypanosomiasis but,
      surprisingly, are highly refractory to trypanosome parasite infection. In
      populations of wild caught flies, it is rare to find mature salivarian and
      mouthpart parasite infection rates exceeding 1 and 15%, respectively. This
      inherent refractoriness persists throughout the lifespan of the fly, although
      extreme starvation and suboptimal environmental conditions can cause a reversion
      to the susceptible phenotype. The teneral phenomenon is a phenotype unique to
      newly emerged, previously unfed tsetse, and is evidenced by a profound
      susceptibility to trypanosome infection. This susceptibility persists for only a
      few days post-emergence and decreases with fly age and bloodmeal acquisition.
      Researchers investigating trypanosome-tsetse interactions routinely exploit this
      phenomenon by using young, unfed (teneral) flies to naturally boost trypanosome
      establishment and maturation rates. A suite of factors may contribute, at least
      in part, to this unusual parasite permissive phenotype. These include the
      physical maturity of midgut barriers, the activation of immunoresponsive tissues
      and their effector molecules, and the role of the microflora within the midgut of
      the newly emerged fly. However, at present, the molecular mechanisms that
      underpin the teneral phenomenon still remain unknown. This review will provide a
      historical overview of the teneral phenomenon and will examine immune-related
      factors that influence, and may help us better understand, this unusual
      phenotype. 

PMID- 24312904
TI  - Gamma knife surgery as monotherapy with clinically relevant doses prolongs
      survival in a human GBM xenograft model.
AB  - OBJECT: Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs).
      However, patients have then usually undergone multimodal treatment, which makes
      it difficult to specifically validate GKS independent of established treatments.
      Thus, we developed an experimental brain tumor model to assess the efficacy and
      radiotoxicity associated with GKS. METHODS: GBM xenografts were implanted
      intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats
      were allocated to GKS, with margin doses of 12 Gy or 18 Gy, or to no treatment.
      Survival time was recorded, tumor sections were examined, and radiotoxicity was
      evaluated in a behavioral open field test. RESULTS: In the first series, survival
      from the time of implantation was 96 days in treated rats and 72 days in controls
      (P < 0.001). In a second experiment, survival was 72 days in the treatment group
      versus 54 days in controls (P < 0.006). Polynuclear macrophages and fibrosis was
      seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed
      less mobility than GKS-treated animals in the open field test 4 weeks after
      treatment (P = 0.04). CONCLUSION: GKS administered with clinically relevant doses
      prolongs survival in rats harboring GBM xenografts, and the associated toxicity
      is mild.

PMID- 24312905
TI  - Lithium chloride enhances cathepsin H expression and BMP-4 degradation in
      C3H10T1/2 cells.
AB  - The effect of canonical Wnt/beta-catenin signaling on chondrogenic
      differentiation induced by transfection of BMP4 expressing plasmid was analyzed.
      Lithium chloride (LiCl) which mimics canonical Wnt/beta-catenin signaling was
      added to cells transfected with BMP4 expressing plasmid. Although BMP4 mRNA
      expression was not affected by LiCl, LiCl decreased BMP4 protein accumulation.
      Gene expression analysis exhibited upregulation of cathepsin H by LiCl treatment.
      Gene silencing of cathepsin H enhanced BMP4 protein accumulation from BMP4
      expressing cells. These results suggested that cathepsin H is regulated by
      Wnt/beta-catenin signaling and plays an important role in the regulation of BMP4
      biological activity.

PMID- 24312900
TI  - Shared and distinct mechanisms of iron acquisition by bacterial and fungal
      pathogens of humans.
AB  - Iron is the most abundant transition metal in the human body and its
      bioavailability is stringently controlled. In particular, iron is tightly bound
      to host proteins such as transferrin to maintain homeostasis, to limit potential
      damage caused by iron toxicity under physiological conditions and to restrict
      access by pathogens. Therefore, iron acquisition during infection of a human host
      is a challenge that must be surmounted by every successful pathogenic
      microorganism. Iron is essential for bacterial and fungal physiological processes
      such as DNA replication, transcription, metabolism, and energy generation via
      respiration. Hence, pathogenic bacteria and fungi have developed sophisticated
      strategies to gain access to iron from host sources. Indeed, siderophore
      production and transport, iron acquisition from heme and host iron-containing
      proteins such as hemoglobin and transferrin, and reduction of ferric to ferrous
      iron with subsequent transport are all strategies found in bacterial and fungal
      pathogens of humans. This review focuses on a comparison of these strategies
      between bacterial and fungal pathogens in the context of virulence and the iron
      limitation that occurs in the human body as a mechanism of innate nutritional
      defense. 

PMID- 24312906
TI  - Phylogeny, functional annotation, and protein interaction network analyses of the
      Xenopus tropicalis basic helix-loop-helix transcription factors.
AB  - The previous survey identified 70 basic helix-loop-helix (bHLH) proteins, but it
      was proved to be incomplete, and the functional information and regulatory
      networks of frog bHLH transcription factors were not fully known. Therefore, we
      conducted an updated genome-wide survey in the Xenopus tropicalis genome project
      databases and identified 105 bHLH sequences. Among the retrieved 105 sequences,
      phylogenetic analyses revealed that 103 bHLH proteins belonged to 43 families or
      subfamilies with 46, 26, 11, 3, 15, and 4 members in the corresponding
      supergroups. Next, gene ontology (GO) enrichment analyses showed 65 significant
      GO annotations of biological processes and molecular functions and KEGG pathways
      counted in frequency. To explore the functional pathways, regulatory gene
      networks, and/or related gene groups coding for Xenopus tropicalis bHLH proteins,
      the identified bHLH genes were put into the databases KOBAS and STRING to get the
      signaling information of pathways and protein interaction networks according to
      available public databases and known protein interactions. From the genome
      annotation and pathway analysis using KOBAS, we identified 16 pathways in the
      Xenopus tropicalis genome. From the STRING interaction analysis, 68 hub proteins
      were identified, and many hub proteins created a tight network or a functional
      module within the protein families. 

PMID- 24312907
TI  - Analysis of pregnancy-associated plasma protein A production in human adult
      cardiac progenitor cells.
AB  - IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability
      in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease
      acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We
      have previously shown that IGFs and IGFBPs are produced by human adult cardiac
      progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in
      cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays,
      we firstly report that PAPP-A is produced and secreted in surprisingly high
      amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A
      is secreted in relevant concentrations in haCPC-conditioned media, while the
      enzymatically inactive PAPPA/proMBP complex is not detectable in the same media.
      Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as
      cell associated, suggesting that the previously described complex formation at
      the cell surface does not occur easily, thus positively affecting IGF signalling.
      Therefore, our results strongly support the importance of PAPP-A for the
      IGFs/IGFBPs/PAPP-A axis in CPCs biology. 

PMID- 24312908
TI  - Indomethacin-enhanced anticancer effect of arsenic trioxide in A549 cell line:
      involvement of apoptosis and phospho-ERK and p38 MAPK pathways.
AB  - BACKGROUND: Focusing on novel drug combinations that target different pathways
      especially apoptosis and MAPK could be a rationale for combination therapy in
      successful treatment of lung cancer. Concurrent use of cyclooxygenase (COX)
      inhibitors with arsenic trioxide (ATO) might be a possible treatment option.
      METHODS: Cytotoxicity of ATO, dexamethasone (Dex), celecoxib (Cel), and
      Indomethacin (Indo) individually or in combination was determined at 24, 48, and
      72 hrs in A549 lung cancer cells. The COX-2 gene and protein expression, MAPK
      pathway proteins, and caspase-3 activity were studied for the most cytotoxic
      combinations. RESULTS: The IC50s of ATO and Indo were 68.7 MUmol/L and 396.5
      MUmol/L, respectively. Treatment of cells with combinations of clinically
      relevant concentrations of ATO and Indo resulted in greater growth inhibition and
      apoptosis induction than did either agent alone. Caspase-3 activity was
      considerably high in the presence of ATO and Indo but showed no difference in
      single or combination use. Phosphorylation of p38 and ERK1/2 was remarkable in
      the concurrent presence of both drugs. CONCLUSIONS: Combination therapy with ATO
      and Indo exerted a very potent in vitro cytotoxic effect against A549 lung cancer
      cells. Activation of ERK and p38 pathways might be the mechanism of higher
      cytotoxic effect of ATO-Indo combination.

PMID- 24312909
TI  - The role of bone marrow mesenchymal stem cells in the treatment of acute liver
      failure.
AB  - OBJECTIVE: This study is to investigate the effects of bone marrow mesenchymal
      stem cell (BMSC) transplantation on acute liver failure (ALF). METHODS: BMSCs
      were separated from rat bone marrow, cultured, and identified by flow cytometry.
      Rat model with ALF was established by injecting D-galactosamine and
      lipopolysaccharide. Rats were randomly divided into the control group and BMSC
      transplantation group. The serum levels of alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) were measured at 24 h, 120 h, and 168 h after
      BMSC transplantation. Apoptosis was detected by TUNEL assay. The expression of
      VEGF and AFP proteins was detected by immunofluorescence. Caspase-1 and IL-18
      proteins and mRNA were detected by immunohistochemistry and RT-PCR. RESULTS:
      Compared with the control group, levels of ALT, AST, caspase-1 and IL-18
      proteins, and mRNA in the transplantation group were significantly lower at 120 h
      and 168 h after BMSCs transplantation. Apoptosis was inhibited by BMSCs
      transplantation. The VEGF protein levels were increased with the improvement of
      liver function, and the AFP protein levels were increased with the deterioration
      of the liver function after BMSCs transplantation. CONCLUSIONS: BMSCs
      transplantation can improve liver function and inhibit hepatocyte apoptosis as
      well as promote hepatocyte proliferation in rat model with ALF.

PMID- 24312910
TI  - Clinical evaluation of CyberKnife in the treatment of vestibular schwannomas.
AB  - OBJECTIVE: This study assessed the posttreatment tumor control and auditory
      function of vestibular schwannoma (VS) patients after CyberKnife (CK) and
      analyzed the possible prognostic factors of hearing loss. METHODS: We
      retrospectively studied 117 VS patients, with Gardner-Robertson (GR)
      classification grades I to IV, who underwent CK between 2006 and 2012. Data
      including radiosurgery treatment parameters, pre- and postoperative tumor size,
      and auditory function were collected and examined. RESULTS: With CK, 117 patients
      had excellent tumor control rates (99.1%), with a mean imaging followup of 61.1
      months. Excluding 52 patients (GR III-IV pretreatment), 53 (81.5%) of the
      remaining 65 patients (initial GR I-II) maintained GR I or II hearing after CK,
      with a mean audiometric followup of 64.5 months. Twelve patients experienced
      hearing degradation (91.6% were GR II pretreatment); they appeared to have
      significantly larger tumor sizes, significantly smaller cochlear sizes, and
      higher prescribed cochlear doses, compared to the patients with preserved
      hearing. CONCLUSION: Our data showed that CK treatment provided an excellent
      tumor control rate and a comparable hearing preservation rate in VS patients.
      Patients with pretreatment GR II hearing levels, larger tumor volumes, smaller
      cochlear sizes, and higher prescribed cochlear doses may have poor hearing
      prognoses.

PMID- 24312911
TI  - The evolutionary pattern and the regulation of stearoyl-CoA desaturase genes.
AB  - Stearoyl-CoA desaturase (SCD) is a key enzyme that converts saturated fatty acids
      (SFAs) to monounsaturated fatty acids (MUFAs) in the biosynthesis of fat. To
      date, two isoforms of scd gene (scd1 and scd5) have been found widely existent in
      most of the vertebrate animals. However, the evolutionary patterns of both
      isofoms and the function of scd5 are poorly understandable. Herein, we aim to
      characterize the evolutionary pattern of scd genes and further predict the
      function differentiation of scd genes. The sequences of scd genes were highly
      conserved among eukaryote. Phylogenetic analysis identified two duplications of
      scd gene early in vertebrate evolution. The relative rate ratio test, branch
      specific dN/dS ratio tests, and branch-site dN/dS ratio tests all suggested that
      the scd genes were evolved at a similar rate. The evolution of scd genes among
      eukaryote was under strictly purifying selection though several sites in scd1 and
      scd5 were undergone a relaxed selection pressure. The variable binding sites by
      transcriptional factors at the 5'-UTR and by miRNAs at 3'-UTR of scd genes
      suggested that the regulators of scd5 may be different from that of scd1. This
      study promotes our understanding of the evolutionary patterns and function of SCD
      genes in eukaryote. 

PMID- 24312912
TI  - Prediction of gene phenotypes based on GO and KEGG pathway enrichment scores.
AB  - Observing what phenotype the overexpression or knockdown of gene can cause is the
      basic method of investigating gene functions. Many advanced biotechnologies, such
      as RNAi, were developed to study the gene phenotype. But there are still many
      limitations. Besides the time and cost, the knockdown of some gene may be lethal
      which makes the observation of other phenotypes impossible. Due to ethical and
      technological reasons, the knockdown of genes in complex species, such as mammal,
      is extremely difficult. Thus, we proposed a new sequence-based computational
      method called kNNA-based method for gene phenotypes prediction. Different to the
      traditional sequence-based computational method, our method regards the
      multiphenotype as a whole network which can rank the possible phenotypes
      associated with the query protein and shows a more comprehensive view of the
      protein's biological effects. According to the prediction result of yeast, we
      also find some more related features, including GO and KEGG information, which
      are making more contributions in identifying protein phenotypes. This method can
      be applied in gene phenotype prediction in other species. 

PMID- 24312914
TI  - Cellular microenvironment in human pathologies.

PMID- 24312915
TI  - Pharmacological application of antiradical compound properties.

PMID- 24312916
TI  - [Schizophrenia after forty and its relation with estrogens].
AB  - There has been a lot of interest in the many aspects of women's mental health
      especially after Kraepelin's description of gender differences in 1896 and the
      implication of gonad hormones in explaining these differences. Studies on the
      effects of hormonal changes in mental health have mainly been focused on the
      various phases of the menstrual cycle, pregnancy and postpartum period; however,
      there is little research regarding menopause. During this period women are at
      risk of developing a new schizophrenic illness the so-called 'second peak'.
      Research has shown that estrogen acts as a protective factor due to its anti
      dopaminergic properties, thus providing an explanation for the risk increase of a
      new psychotic disorder during menopause. This review article highlights the
      importance of a clear understanding of this phase of life in patients suffering
      from or who present a risk of developing schizophrenia. 

PMID- 24312917
TI  - [Study on drug use among students in the province of Valencia, Spain].
AB  - Drug use among youth has increased in recent years dramatically during
      adolescence, a key phase in the integral development of the individual. The main
      aim of this cross-sectional, descriptive study was to assess the current drug use
      trends, as a function of age and gender among secondary education students from
      representative centers in the Valencia province during the school year 2009-2010.
      A total of 328 adolescents, 44.8% (n=147) males and 55.2% (n=181) females, with a
      mean age of 15.61 (SD 2.5) years, divided in three age groups: 12-14 years old
      (n=134, 40.9%), 14-18 years old (n=123, 37.5%), and older than 18 years of age
      (n=71, 21.6%) participated in the study. Alcohol and tobacco, followed by
      cannabis, were the substances more commonly used by the secondary education
      students. There were statistically significant differences between the three age
      groups in lifetime use of tobacco, alcohol, cannabis, cocaine, amphetamines and
      tranquilizers. The highest prevalences were observed in students older than 18
      years of age, therefore evidencing a common pattern of increase in substance use
      with age. Alcohol and tobacco use were significantly higher among girls compared
      to boys, while males more commonly used inhalants and opioids. Therefore, it
      appears essential to promote prevention campaigns at earlier ages, when
      adolescents are more vulnerable to initial substance use, and adapted to the
      specific needs of the diverse populations of school age children. 

PMID- 24312918
TI  - [Enduring pain I. Nosology and epidemiology].
AB  - Pain disorders are extraordinarily prevalent throughout clinical medicine, and
      are highly co-morbid with various psychiatric disorders, particularly those
      including depression or anxiety. Assessment of such patients tends to be based on
      diagnostic criteria that may not reflect the complexity of the clinical problem
      and can result in prioritizing somatic aspects of painful syndromes at the
      expense of psychiatric aspects or, conversely, over-emphasize psychiatric
      aspects. In the first part of this overview we consider current nosological
      perspectives and their potential clinical consequences, epidemiological data that
      underscore the association of comorbid painful and affective or anxious
      syndromes, and consider the importance of psychiatric assessment and treatment of
      such patients. The major overlap between pain disorders and psychiatric
      disorders, as well as the unsatisfactory state of treatments available for
      chronic pain syndromes, encourage a comprehensive approach to assessing and
      clinically managing patients with chronic pain. Many programs for pain disorder
      patients offer narrowly specialized treatment options. To be preferred are multi
      disciplinary teams with expertise in internal medicine, neurology, pain
      management, and rehabilitation, as well as psychology and psychiatry. In the
      second part of this overview, we propose that psychiatrists can serve a key role
      in leading comprehensive assessment and management of complex and challenging
      pain-psychiatric patients who are typically only partially responsive to
      available treatments. 

PMID- 24312919
TI  - [Enduring pain II. Treatment].
AB  - Pain disorders present highly challenging therapeutic problems, owing in part to
      complex co-morbidities associated with pain disorders, notably including
      psychiatric disorders characterized by depressed mood or anxiety. Many treatments
      are employed to treat pain-disorder patients, and most are unsatisfactory.
      Virtually all analgesic medicines in long-term use provide only partial efficacy
      and present substantial risks of adverse effects, loss of benefit over time, or
      dependency and risk of abuse. Commonly employed drugs with analgesic properties
      include non-opioids (mainly nonsteroidal anti-inflammatory agents [NSAIDs] or
      acetaminophen), many natural or synthetic opioids (including opiates and
      phenylpiperidines), some antidepressants (especially those with noradrenergic
      activity), a few anticonvulsants, skeletal muscle relaxants or topical remedies,
      and a growing variety of experimental treatments. The major overlap between pain
      and psychiatric disorders, as well as the currently unsatisfactory state of
      treatments available for chronic pain syndromes, encourage a comprehensive
      approach to assessment and clinical management of patients with chronic pain.
      Many current treatment programs for pain disorder patients offer narrowly
      specialized and incomplete treatment options. Ideally however, such care should
      be provided by multi-disciplinary teams with expertise in neurology, general
      medicine, pain management, physical medicine and rehabilitation, as well as
      psychiatry. Psychiatrists as well as pain specialists can serve an essential role
      in leading comprehensive assessment and general management of such complex and
      challenging patients who are typically only partially responsive to available
      treatments. 

PMID- 24312913
TI  - A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast
      cancer.
AB  - Breast cancer (BC) is the most common cancer of women all over the world. BRCA1
      and BRCA2 gene mutations comprise the most important genetic susceptibility of
      BC. Except for few common mutations, the spectrum of BRCA1 and BRCA2 mutations is
      heterogeneous in diverse populations. 185AGdel and 5382insC are the most
      important BRCA1 and BRCA2 alterations which have been encountered in most of the
      populations. After those Ashkenazi founder mutations, 300T>G also demonstrated
      sparse frequency in African American and European populations. This review
      affords quick access to the most frequent alterations among various populations
      which could be helpful in BRCA screening programs. 

PMID- 24312920
TI  - [Self mutilation in borderline personality disorder. Pain as a self-treatment? A
      case report].
AB  - The objective of this article is to highlight the complexity of the phenomenon of
      self-mutilation, or self-injury, among individuals with Borderline Personality
      Disorder. The practice of self-mutilation in this population is strikingly
      common, with some authors estimating the prevalence to be up to 75%. Particularly
      noteworthy is the high percentage of patients with Borderline Personality
      Disorder who state that the act of self-injury has an analgesic effect. This
      article lays out a few theories that support this finding. Frequently, patients
      who self-mutilate do not aim to commit suicide but rather, to relieve internal
      tension. However, clinical interventions are often largely centered on
      interpreting the self-injurious act as a suicide attempt, with complex
      therapeutic consequences. A clinical vignette is presented to highlight the
      aforementioned issues. 

PMID- 24312921
TI  - [What does language tell us about pain?].
AB  - In this article the etymology and meaning of words relating to pain, suffering,
      compassion, etc. are being explored. An experience is reported about how pain and
      suffering may be both confronted in different ways from a clinically point of
      view, with different results for the patient. Different concepts about the
      meaning of pain according to classical, evolutionary and contemporary theories
      are being briefly examined. Also the different implications of psychological and
      physical pain are being mentioned, quoting authors such as Le Breton, Escardo,
      Sacks and Borges. Finally, a detailed analysis about the distinctions between
      empathy, sympathy and compassion is brought to focus, as well as the relevance of
      these notions in the medical approach. By means of conclusion, there is a
      reference to the typical attitude of the modern mind, denying and resisting pain,
      and philosophical texts (Lao-Tze, Plato, Stefan Zweig) are quoted, warning us
      about the limits and dangers of such attitude. 

PMID- 24312922
TI  - [Pain: an approach to its understanding and management].
AB  - The article highlights that pain is a human experience that goes beyond the
      merely physical, and notes the importance of understanding that only the sufferer
      is able to describe and quantify it. Describe the pain not only as a symptom,
      more than that is feeling, and emotion and emphasizes the role of the doctor
      patient relationship in their approach. It emphasizes the neurobiological,
      psychosocial and spiritual dimensions of pain and the need for an
      interdisciplinary approach. Upgrade contributions of neurobiology in brain
      modulation of pain and the origins of the levels of sensitivity and pain
      tolerance. Rescue the importance of recognizing the total pain and suffering in
      the pain therapeutic approach, and highlights the difficulties of the health
      team. Review various international human rights instruments, to support the
      argument that the patient should be protected from the inadequate treatment of
      pain. Lack of education and updating of health professionals is another major
      problem. Finally emphasizes that pain relief is a human right and the inadequacy
      of treatment is a serious ethical lapse. 

PMID- 24312923
TI  - [Conditions, controversies and contradictions between Central Sensitivity
      Syndrome and Depressive Disorders].
AB  - We present a description of the Central Sensitivity Syndrome (CSS) and some of
      its main components such as Multiple Chemical Sensitivity Syndrome, Chronic
      Fatigue Syndrome and Fibromyalgia. We review the changes in pain perception,
      describing the physiology and pathophysiology of the painful experience from the
      medulla horn to the CNS. We explain the theory of central sensitization as the
      basis to the syndrome. We refer to the differences between fibromyalgia and
      depressive disorders, is spite of their frequent presentation in comorbidity. We
      state the main clinical and neurobiological differences. We point out the main
      psychoneuroimmunoendocrinologic differences such as adrenal activity
      (hypoactivity vs. hyperactivity, DST hypersuppressive response vs. DST non
      suppression, hypersensitivity of central glucocorticoid receptors vs.
      desensitization of these, among others), thyroid (probable reverse T3 vs. flat
      stimuli TSH response curve) and growth hormone secretion (probable increase vs.
      disruption of normal circadian rhythm) that makes CSS resemble PTSD. We describe
      differential changes in sleep patterns (alpha-delta intrusion vs. altered sleep
      time, REM latency, and stage 3/4) and immunological disturbances almost opposite
      in each pathological entity. We finally argue which medical specialty should
      treat these complex syndromes.

PMID- 24312924
TI  - [Thinking Hystery in 1900's Buenos Aires: the "hysterical laugh" in Hystery and
      suggestion of Jose Ingenieros].

PMID- 24312925
TI  - [The hysterical laugh].

PMID- 24312933
TI  - Integration of uniform porous shell layers in very long pillar array columns
      using electrochemical anodization for liquid chromatography.
AB  - Electrochemical anodization has been applied to grow porous shell layers of 300
      nm (30 nm pores) in 5 MUm diameter pillar array columns (PACs) with a spacing of
      2.5 MUm. Using turn structures preceded and followed by the flow distributor
      structures recently introduced by our group and filled with radially elongated
      pillars, columns with quasi unlimited channel lengths could be conceived. The
      uniformity of the porous PAC was assessed by determining local plate heights
      along the channel, which appeared to be constant. Minimal (absolute) plate
      heights (H) between 4 and 6 MUm were obtained at optimal flow rates when imposing
      increasing retention factors. Upon measuring the surface area involved in
      chromatographic retention as an indicator of the available surface area, an
      increase in the surface area by a factor of about 30 compared to that of non
      anodized pillars was found. On reconfiguring a commercial HPLC instrument to
      enable on-chip injections, 90% of the performance (expressed in theoretical
      plates) could be maintained for a 1 m column, while for a 25 cm column severe
      losses were still observed. As the corresponding pressure drop for optimal
      operation of retained components is on the order of 10 bar per m only, portable
      and cheaper HPLC devices with high efficiencies become realistically conceivable.

PMID- 24312935
TI  - Response.

PMID- 24312936
TI  - Response.

PMID- 24312937
TI  - Response.

PMID- 24312938
TI  - Response.

PMID- 24312939
TI  - Response.

PMID- 24312940
TI  - Abstracts of the 43rd Critical Care Congress. January 9-13, 2013. San Francisco,
      California, USA.

PMID- 24312941
TI  - Millen Gordon Mackay.

PMID- 24312943
TI  - Popular science: Get the word out.

PMID- 24312944
TI  - Abstracts of the 20th International Symposium on Radiopharmaceutical Sciences.
      May 12-17, 2013. Jeju, South Korea.

PMID- 24312945
TI  - Abstracts of the American College of Neuropsychopharmacology (ACNP) 52nd Annual
      Meeting. December 8-12, 2013. Hollywood, Florida, USA.

PMID- 24312947
TI  - Auer rod-like inclusions in kappa light chain myeloma.

PMID- 24312948
TI  - Favism in a 15-month-old baby.

PMID- 24312949
TI  - Endothelial coculture with mesenchymal stem cells on nanotopography to direct
      osteogenesis.

PMID- 24312950
TI  - Periodicity is important in stem cell response.

PMID- 24312951
TI  - Hydrogel nanoparticles for drug delivery.

PMID- 24312953
TI  - Call the cops.

PMID- 24312952
TI  - [The evolution of adenoidectomy].
AB  - The critical analysis of publications concerning methods designed for the
      surgical treatment of adenoids is presented. Various surgical techniques are
      considered with special reference to their indications for use, invasiveness,
      effectiveness, and safety. Recent developments in this field give evidence that
      evolution of adenoidectomy brought about highly efficacious (up to 99%) mini
      invasive and safe surgical procedures producing the minimal risk of relapses and
      postoperative complications. All these advancements became possible due to the
      introduction of endoscopic intraoperative control, general anesthesia, and the
      use of modern surgical instruments. Modern approaches make unnecessary radical
      removal of the lymphoid tissue.

PMID- 24312954
TI  - The FDA and me.

PMID- 24312955
TI  - Lecture notes.

PMID- 24312956
TI  - Planetary science: Lunar conspiracies.

PMID- 24312957
TI  - [Pre- and post-conditioning phenomena: the protective physiological mechanisms in
      the aspect of pathogenesis and the theory of treatment of ENT pathology].
AB  - The objective of the present work was to expose the universal general biological
      significance of the protective pre- and postconditioning phenomena and to provide
      an insight into the possibility of application of therapeutic modalities based on
      these effects in current otorhinolaryngological practice. Pre- and
      postconditioning phenomena (Pre-C and Post-C respectively) began to be studied as
      protective physiological mechanisms since the 1980s, first in cardiology and
      thereafter in other fields of experimental medicine. At the same time, their
      protective properties had been known and intuitively used much earlier among the
      established human cultural and social stereotypes, psychophysical training
      techniques, and methods of traditional and empirical medicine. The widespread
      application of these phenomena gives evidence of their universal biological
      nature as factors involved in the interactions between the organism and pathogens
      (including co-morbidity), the process leading to the enhancement of non-specific
      resistance, mechanisms underlying realization of pharmacodynamic effects of a
      number of pharmaceutical products,etc. The understanding of the protective
      potential of PreC and PostC dictates the necessity to revise and further
      elaborate the present-day strategy of prophylaxis and treatment of the most
      serious chronic ENT diseases.

PMID- 24312958
TI  - [Modern principles of the treatment and prevention of diseases of external ear].
AB  - The problems of diagnostics, treatment and prophylaxis of inflammatory diseases
      of the external ear remain a challenge for practical otorhinolaryngology. The
      number of patients presenting with this pathology is still very high despite the
      availability ofa great variety of pharmacological products for their management.
      The problem of external otitis arises from its high incidence in conjunction with
      the poor effectiveness of various medicamental and non-medicamental therapeutic
      modalities for its treatment.The aforesaid confirms the importance and relevance
      of the search for the new methods of treatment of this pathology as well as
      effective therapeutic and preventive agents for this purpose. Of primary
      importance from the standpoint of prophylaxis of various diseases of external ear
      is providing adequate care to the patients with trivial cerumen impaction that is
      a risk factor of external otitis leading to the development of skin lesions in
      the auditory passage and inflammation in the case of self-removal of the earwax.

PMID- 24312959
TI  - Can we regrow a human arm? An overview and summary.

PMID- 24312960
TI  - Dash for gas leaves Earth to fry.
AB  - The aggressive expansion of 'unconventional natural gas development' - more
      widely known as 'fracking' - has triggered protests across Europe. The concern is
      not just the direct impact on the environment but the production of fossil fuel
      in quantities we can no longer afford to burn, along with the side effect that
      the availability of cheap gas undermines the economic viability of sustainable
      energies.

PMID- 24312961
TI  - Angelika Amon.

PMID- 24312962
TI  - Hiring the right way.

PMID- 24312963
TI  - Does education matter? Yes!

PMID- 24312964
TI  - Thumbs up for mandatory  flu shots.

PMID- 24312965
TI  - Reply: To PMID 23778064.

PMID- 24312966
TI  - Reply: To PMID 23546924.

PMID- 24312967
TI  - Abolishing the companionship exemption: good intentions but harmful results.

PMID- 24312968
TI  - Highlights of the 2013 Financial Managers Conference.

PMID- 24312969
TI  - HHFMA Leadership Panel: The future belongs to home care and hospice.

PMID- 24312970
TI  - Health Care Leadership Panel: The views of health care industry stakeholders.

PMID- 24312971
TI  - Care integration and network models: how to become a player.

PMID- 24312972
TI  - Modeling hospice changes to prepare for Medicare reimbursement and care delivery
      reform.

PMID- 24312973
TI  - Medicaid home care: adjusting to the changes successfully.

PMID- 24312974
TI  - [Parotid gland neoplasm].

PMID- 24312975
TI  - [Laryngectomy and neck dissection].

PMID- 24312976
TI  - [Classification of neck dissection].

PMID- 24312977
TI  - [Caution for treatment of the patient taking anti-platelet and anti-coagulant].

PMID- 24312978
TI  - [Liver, pancreas, biliary tract cancer].

PMID- 24312979
TI  - [I. Diagnosis and treatment for hepatoma].

PMID- 24312981
TI  - [III. Biliary tract cancer].

PMID- 24312980
TI  - [II. Intrahepatic cholangiocarcinoma].

PMID- 24312982
TI  - [IV. Neoadjuvant therapy for cholangiocarcinoma].

PMID- 24312983
TI  - [V. Current status of chemotherapy for carcinoma of the ampulla open Vater].

PMID- 24312984
TI  - [VI. Improvement of combined modality therapy for pancreas cancer].

PMID- 24312985
TI  - [Discussion about Biomilar development: Filgrastim BS injection and its
      applications in clinical practice].

PMID- 24312986
TI  - Health workforce needs: projections complicated by practice and technology
      changes.
AB  - As population growth and the aging of the overall population increase demand for
      health care, policymakers and analysts posit whether sufficient health care
      providers will be able to meet that demand. Some argue there are too few
      providers already; others say our current supply-demand problems lie with
      efficiency. But suppose both are correct? Perhaps the real challenge is to
      understand how physician practices are changing in response to market forces such
      as payment changes, provider distributions, and technology innovations. This
      issue brief reviews what is known about evolving practice organizations,
      professional mixes, information technology support, and the implications of these
      and other factors for public workforce policies.

PMID- 24312987
TI  - Seeking value in Medicare: performance measurement for clinical professionals.
AB  - The Medicare program, despite its reputation of being a bill payer with little
      regard to the worth of the services it buys, has begun to put in place a range of
      programs aimed at assessing quality and value, with more to come. Attention to
      resource use and cost is nascent. The issues are complex, and it is no surprise
      that there is a level of contention between providers and regulators, even though
      both profess commitment to improved quality. This paper summarizes the quality
      and value programs that apply to physicians and other clinical professionals, as
      well as programs designed to encourage the adoption of technology to support
      quality improvement. Participation in all is voluntary. However, a decision not
      to participate increasingly carries a financial penalty, as Congress (and, by
      extension, the U.S. Department of Health and Human Services, or HHS) tries to
      encourage behavior it cannot force.

PMID- 24312988
TI  - What happens when Medicare cuts hospital prices? Assessing the impact on
      inpatient discharges among the elderly.
AB  - Key findings. (1) Between 1995 and 2009, growth in Medicare inpatient prices
      varied widely across hospital markets. Faster growth typically occurred in less
      urban areas that had a large market share of for-profit hospitals. (2) By 2008
      2009, elderly patients were going to the hospital at the same rate as in the mid
      1990s, but their stays were much shorter, and they received much more intensive
      services. (3) Medicare price cuts, largely attributable to the Balanced Budget
      Act of 1997, were associated with a decrease in the num-ber of elderly discharges
      and a decrease in the number of staffed hospital beds, highlighting possible
      effects of hospital price cuts under health reform.

PMID- 24312989
TI  - Clinical management apps: creating partnerships between providers and patients.
AB  - The market for health applications, or apps, on mobile devices is growing rap
      idly, with over 40,000 currently in use. One type of app technology--clinical
      manage-ment apps--enable patients and providers to work together to manage
      chronic conditions, particularly diabetes and asthma. These apps are mostly used
      by health plans and large health care organizations with an interest in improving
      outcomes and controlling costs. Challenges to broader adoption of apps include
      the lack of objective research to evalu-ate outcomes, uncertainty about how to
      pay for and encourage the use of cost-effective apps, and the absence of a
      regulatory framework that standardizes development to ensure performance. If this
      infrastructure is developed, apps may serve as a catalyst to stimulate the
      transformation of health care generally and target low-income populations to
      expand access to care and help reduce health disparities.

PMID- 24312990
TI  - Robert Remak (1815-1865): discoverer of the fungal character of dermatophytoses.
AB  - Robert Remak was the first scientist to undertake successful research on fungal
      skin infections. A neurologist, physiologist, and embryologist, Remak was the
      first to observe the fungal changes causing the disease of favus; however, he
      gave credit for the discovery to Professor Johann Schonlein and denied all
      attempts by others to credit him with the discovery by calling them a mistake. He
      named the disease Achorion schonleinii; however, over time, the name was changed
      to Trichophyton schoenleinii. Remak also described axial fibers encased in a
      medullary sheath and was the first to recognize nonmyelated (sympathetic) nerve
      fibers, today called fibers of Remak. He demonstrated the existence of the
      medullary nerve sheath and its production in the process of structured cell
      division. Remak also was the first to demonstrate that the cerebral cortex
      consists of six layers and to assert that there are three germ layers in the
      early embryo and not four.

PMID- 24312991
TI  - We must move with the times in the way we communicate with current and future
      perioperative practitioners.

PMID- 24312992
TI  - Pursuit of happiness.

PMID- 24312993
TI  - Understanding public protection: more of a moral maze than a simple answer.

PMID- 24312994
TI  - Carers' perceptions of the enhanced recovery programme in colorectal surgery.
AB  - The Enhanced Recovery Programme (ERP) is widely used, especially within
      colorectal surgery. It is structured around a patient centred decision making
      process, and the evidence to support the ERP is well documented. Much of the
      literature focuses on patients' perceptions of the ERP, with qualitative
      evaluation of their experiences. However, the experience of the ERP from a
      carer's perspective has yet to be explored.

PMID- 24312995
TI  - Emergence delirium.
AB  - Emergence delirium (ED) is a well-known phenomenon in the postoperative period.
      However, the literature concerning this clinical problem is limited. This review
      evaluates the literature with respect to epidemiology and risk factors. Treatment
      strategies are discussed. The review concludes that there is a need for
      guidelines concerning diagnosis and treatment of ED. Risk factors should be
      investigated further in the clinical setting in the future.

PMID- 24312996
TI  - Effects of food colouring added to 2% chlorhexidine gluconate and 70% alcohol for
      surgical site antisepsis.
AB  - Preoperative cleansing of a patient's skin with chlorhexidine gluconate (CHG) in
      alcohol is superior to cleansing with povidone-iodine for preventing surgical
      site infection (SSI) after clean-contaminated surgery (Darouilche et al 2010).
      However, 2% CHG in 70% alcohol, tinted pink, is colourless when applied to limbs
      for surgery and complete coverage cannot be assured. The purpose of the study was
      to evaluate the efficacy of food colouring added to CHG in preoperative skin
      preparation. Two hundred and eight subjects were randomly selected from a
      population of healthy young adults and were given a questionnaire. They were
      excluded if they had a known allergy to CHG or food dye, a current infection at
      the preparation site, or previous preparation with CHG at the site. CHG with food
      dye additive was applied on the subject's left foot while CHD without the
      additive was applied on the right. Skin swabs were then taken of both feet and
      plated on blood agar plates and incubated for 48 hours. Assessment of growth was
      compared. Patients treated with tinted CHG had around 3.4 times (95% CI: 1.5,
      7.8) the risk of a positive bacterial swab compared with those treated with
      untinted CHG. The efficacy of CHG significantly decreased with food colouring
      additive. This is consistent with previous studies conducted on similar
      incompatible substances. In order to have the full efficacy of CHG as a
      preparation, much thought and care needs to be taken to prevent contamination of
      the site and substance.

PMID- 24312997
TI  - Scrub skills audit.
AB  - The aim of this study was to improve the knowledge and understanding of the
      evidence which encompasses extended roles and advanced practice for theatre scrub
      practitioners. The intention was also to develop a local policy and training
      strategy for advanced roles, benchmarked against professional standards (PCC
      2007) and clinical practice audit.

PMID- 24312998
TI  - James Parkinson: Parkinson's disease.
AB  - Parkinson's disease is a condition that anyone with a modicum of medical
      knowledge can recognise in the street--as indeed how it was studied by James
      Parkinson himself. Its three characteristic features are: 1. Increase in the tone
      of the voluntary muscles (rigidity). 2. Slowness of movement (bradykinesis). 3.
      Tremor (the characteristic 'pill rolling' movements of the fingers).

PMID- 24312999
TI  - [Clinical trial of the infant in Japan].

PMID- 24313000
TI  - [5-year-old boy with tuberous sclerosis who presented with acute headache and
      vomiting].

PMID- 24313001
TI  - [CD38 and autism spectrum disorders].
AB  - We have demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase
      activity, plays a critical role in mouse social behavior by regulating the
      release of oxytocin (OXT), which is essential for mutual recognition. When CD38
      was disrupted, social amnesia was observed in Cd38 knockout mice. We investigated
      single nucleotide polymorphisms (SNPs) in the human CD38 gene in autism spectrum
      disorder (ASD) patients. The SNP rs3796863 (A>C) was associated with high
      functioning autism (HFA) in American samples. Although this finding was partially
      confirmed in low-functioning autism subjects in Israel, it has not been
      replicated in Japanese HFA subjects. The second SNP of interest, rs1800561
      (4693C>T), leads to the substitution of an arginine (R) at codon 140 by
      tryptophan (W;R140W) in CD38. This mutation was found in 4 probands of ASD and in
      family members of 3 pedigrees with variable levels of ASD or ASD traits. The
      plasma levels of OXT in ASD subjects with the R140W allele were lower than those
      in ASD subjects lacking this allele. One proband with the R140W allele receiving
      intranasal OXT for approximately 3 years showed improvement in areas of social
      approach, eye contact and communication behaviors, emotion, irritability, and
      aggression. Five other ASD subjects with mental deficits received nasal OXT for
      various periods;three subjects showed improved symptoms, while 2 showed little or
      no effect. These results suggest that SNPs in CD38 may be risk factors for ASD by
      abrogating the OXT function, and that some ASD subjects can be treated with OXT
      in preliminary clinical trials.

PMID- 24313002
TI  - [Immunohistochemical analysis of brainstem functions in autopsy cases of Fukuyama
      congenital muscular dystrophy].
AB  - OBJECTIVE: Sudden unexpected death (SUD) may occur in patients with Fukuyama
      congenital muscular dystrophy (FCMD). In this study, we performed
      immunohistochemical examination of SUD-related functional markers in the
      brainstem of autopsy cases of FCMD, in order to clarify the pathogenesis of SUD.
      METHODS: The examination was conducted on 9 autopsy cases of FCMD, including a
      case of SUD and 3 of acute death (AD) in which SUD was suspected but not
      confirmed. We immunohistochemically examined serial brainstem sections for
      serotonin and catecholamine neurons, neuropeptides, and c-Fos, a neuron
      activation marker. RESULTS: 1) Number of serotonin neurons was reduced in 7
      cases, including the cases of SUD and AD. 2) Expressions of neuropeptides were
      exaggerated in the spinal trigeminal nucleus in 5 cases, including the SUD and AD
      ones. 3) Neurons immunoreactive for c-Fos were found in 3 cases, including the
      SUD and AD cases. 4) The suspected case of SUD showed changes in all SUD markers.
      CONCLUSIONS: Changes in the tested markers were found predominantly in the SUD
      and AD cases, indicating functional fragility in the brainstem of patients with
      FCMD.

PMID- 24313003
TI  - [Treatment with ramelteon for sleep disturbance in severely disabled children and
      young adults].
AB  - OBJECTIVE: The aim of this study was to determine the efficacy and safety of
      ramelteon for severely disabled children and young adults who had already been
      treated for sleep disturbance with melatonin at a dose of 3 mg. METHODS: Eleven
      patients, who were aged between 3-25 years and included 4 patients with cerebral
      palsy, -took 3-8 mg of ramelteon at bedtime, after a one-week of washout period.
      Sleep states were evaluated using sleep diaries recorded by caregivers or using
      actigraphs. RESULTS: Ramelteon was effective in 8 out of the 11 patients.
      Ramelteon was tolerated well except for mild daytime sleepiness in three
      patients. CONCLUSIONS: This preliminary study showed the efficacy and safety of
      ramelteon for sleep disturbance in severely disabled children and young adults.
      Further trials are necessary to determine optimal dosage and safety of ramelteon
      in children.

PMID- 24313004
TI  - [The association of hypocarnitinemia with enteral diets and antiepileptic drugs
      in children and adults with severe physical and mental disabilities].
AB  - OBJECTIVE: To examine the risk factors of hypocarnitinemia and hypocarnitinemic
      symptoms in children and adults with severe physical and mental disabilities.
      METHODS: The status of hypocarnitinemia as well as the related symptoms were
      assessed in a total of 78 children and adults with severe physical and mental
      disabilities who were admitted to National Hospital Organization Iou National
      Hospital. Their enteral diets and the medication of antiepileptic drugs were
      evaluated. RESULTS: Markedly decreased blood carnitine levels were noted in
      patients undergoing an enteral diet without carnitine supplementation as well as
      in those receiving a combination of valproate sodium (VPA) and phenobarbital
      (PB). These hypocarnitinemic patients tended to have more frequent episodes of
      hypoglycemia and hyperammonemia. CONCLUSIONS: Supplemental L-carnitine is needed
      in patients receiving an enteral diet free of carnitine, those with combination
      therapy of VPA and PB under oral feeding conditions, and those who develop
      hyperammonemia during VPA therapy. Patients who received a carnitine-supplemented
      enteral diet maintained their serum carnitine levels with a relatively low
      supplemental dose of carnitine.

PMID- 24313005
TI  - [Sibling cases of severe infantile form of nemaline myopathy with ACTA1-gene
      mutation].
AB  - Severe infantile form of nemaline myopathy is clinically characterized by marked
      muscle hypotonia and weakness with respiratory and feeding difficulties since
      infancy. Recently, mutations in the skeletal muscle alpha-actine gene (ACTA1)
      have been identified in many patients with the nemaline myopathy. We experienced
      two cases of severe infantile form of nemaline myopathy with ACTA1 mutation
      (missence heterozygous mutation;c.553C>T, p.R185C) in siblings presenting with
      different clinical symptoms and courses. The elder brother was a typical "floppy
      infant" at birth. Because he could not suck and swallow at all, he was fed
      completely through a nasogastric tube. At 2 months of age, he developed
      respiratory insufficiency and was placed on a respirator all day. He was
      diagnosed with having nemaline myopathy from his muscle biopsy, which revealed
      marked variation in muscle fiber size with large numbers of nemaline bodies on
      Gomori-trichrome stain. In contrast, the younger brother presented with mild
      muscular hypotonia and feeding difficulty during the neonatal stage;therefore, he
      was partly fed through a nasogastric tube. At 2 months of age, he was admitted to
      our hospital because of respiratory distress, and he required nasal continuous
      positive airway pressure with oxygen followed by noninvasive positive pressure
      ventilation intermittently, mainly at night. He was followed at his home by
      parents with no serious problems;however he unexpectedly died at the age of 15
      months. Although most cases of severe infantile form of nemaline myopathy caused
      by ACTA1 mutations are sporadic and have no family history, we emphasize that
      clinical symptoms are variable in siblings with the same mutation.

PMID- 24313006
TI  - [Acute encephalitis presenting with symmetrical involvement of the bilateral
      basal ganglia].
AB  - A 8-year-old girl was hospitalized with consciousness disturbance and involuntary
      movements five days after the onset of fever. Cranial MRI revealed symmetrical
      involvement of the bilateral basal ganglia with elevated ADC mapping, suggesting
      vasogenic edema.Her clinical symptoms improved with methylprednisolone pulse
      therapy without neurological sequelae. The rapid antigen test for group A beta
      hemolytic streptococcus was positive and serum ASO was elevated. Myelin basic
      protein in cerebrospinal fluid was elevated. We suggest that the
      pathophysiological mechanism in the present case was not necrotic/cytotoxic but
      autoimmune inflammation, which is compatible with acute disseminated
      encephalomyelitis associated with streptococcal infection.

PMID- 24313007
TI  - [Acute encephalopathy associated with human metapneumovirus: a case report].

PMID- 24313008
TI  - [Efficacy and psychiatric adverse events as short-term adjunctive levetiracetam
      for epileptic children with refractory convulsive seizures].

PMID- 24313009
TI  - [Women's health and development].
AB  - Compared to industrialized countries, the maternal mortality rate is 100 times
      higher in resource-poor countries, where every minute a woman dies because she is
      pregnant. Most of these deaths are due to hemorrhage during home delivery. This
      high fatality rate results mainly from a lack of obstetric professionals,
      remoteness, and poverty all of which hinder timely access to emergency obstetric
      care. Four factors can help to reduce maternal mortality: a higher standard of
      living, better education of girls, a lower fertility rate, and better access to
      obstetric professionals.

PMID- 24313010
TI  - [How to reduce maternal mortality?].
AB  - Maternal mortality is still very high in developing countries. A large proportion
      of maternal deaths are due to delayed or substandard emergency obstetric care.
      There is an urgent need to develop and validate interventions designed to improve
      the management of obstetric complications. There is some experimental or quasi
      experimental evidence supporting interventions that reduce delays in the
      treatment of obstetric emergencies in resource-poor settings. Most are community
      based interventions that provide funds for transport and public education, or
      that improve the referral system and medical practices at the different levels of
      care. The most effective measures are facility-based review's of maternal deaths
      and near-misses, and referral interventions. More research is needed to
      understand precisely how these interventions improve maternal and neonatal
      outcomes.

PMID- 24313011
TI  - [Surgical management of obstetric fistulae].
AB  - With three decades of experience in the treatment of obstetric fistulae (OF), the
      authors discuss surgical management of OF secondary to blocked labor (> 48
      hours), the main cause of OF in poor countries. Clinical classification is
      mandatory to ensure the correct indication, with three situations of increasing
      difficulty. The technical principles are simple and few instruments are required.
      Surgical difficulty increases in case of tissue sclerosis, difficult locations,
      and associated lesions (sphincter destruction, recto-anal fistulae, etc.). Group
      I OF can be cured in a single operation, while complex OF require two or more
      surgical procedures for cure or improvement. Better post-surgical care and more
      clinical and surgical research are needed to improve these women's outcomes.
      Despite some progress in the last decade, the situation in poor countries remains
      unacceptable. Prevention is clearly possible, through emergency obstetric care
      and better obstetric skills, as this dramatic complication of dystocia has
      virtually disappeared in rich countries.

PMID- 24313012
TI  - [Lysosomal proteolysis; overview of lysosomal diseases].
AB  - The lysosome plays a key role in recycling other cell organelles and long-lived
      cellular proteins, which undergo continuous turnover. Lying at the hub of
      vesicular pathways, the functions of which are tightly inter-regulated, the
      proteolytic machinery of the lysosome is essential for cellular homeostasis.
      Lysosomal diseases are rare genetic disorders due to deficiencies in one or
      several lysosomal protein(s). Their clinical manifestations are extremely diverse
      and depend on the total or partial nature of the protein deficiency and the
      specific functions of this organelle in different cell types.

PMID- 24313013
TI  - [New insights into intracellular inclusions and intracellular proteolysis].
AB  - Intracellular inclusions seen by the pathologist may have variable significance.
      Although they are excellent markers of proteolytic disorders, they can also be
      due to several other mechanisms. This article examines recent data on the
      morphology, significance and consequences of aging lipofuscins in the brain and
      retina, neurofibrillary tangles and Lewy bodies, and Birbeck granules associated
      with Langerhans histiocytosis. Some of these disorders involve increased protein
      production, misfolding and aggregation, and altered intracellular proteolysis,
      but other cell constituents may also play a role. Proteolytic mechanisms do not
      appear to be involved in the formation of Birbeck granules, which helped to
      reveal the Langerhans origin of histiocytosis X. Analyses of intracellular
      inclusions, together with genetic and epigenetic studies, are highly informative
      in various degenerative diseases.

PMID- 24313014
TI  - [Role of defective intracellular proteolysis in human degenerative diseases].
AB  - Although intracellular protein synthesis has been studied extensively, protein
      degradation and disposal, know as proteolysis, has been relatively neglected.
      Modern studies which led two Nobel prizes (de Duve in 1950 and Herschko, Rose and
      Ciechanover in 1980) established that proteolysis is ensured by two separate but
      complementary mechanisms: lysosomes responsible for auto and heterophagy and the
      Ubiquitin-Proteasome System (UPS). The UPS involves ubiquitin, a small molecule
      consisting of 76 amino acids found in all eukaryotic cells that ensures the
      identification of the protein to be degraded and its transport to the proteasome,
      an intracellular complex with enzymes which degrade unneeded or damaged proteins.
      The proteasome, acting as a composting agent, ensures the enzymatic dissociation
      of the protein. In this degradation process, as infinite screw, ubiquitin,
      peptides and amino acids are released and made available for a new cycle.
      Knowledge of the UPS and its related disorders is continually expanding.
      Concurrent with lysosomes which work in acidic environment, it is currently known
      that the UPS provides 80% to 90% of the proteolysis of the short-life proteins
      and ensures, as chaperon-molecules, the right conformation and hence the correct
      function of the proteins. The proteolytic activity generates abnormal residues
      (tau protein, amyloid and related proteins) and various soluble and insoluble
      wastes. Some are precipitated as inclusion-bodies or aggregosomes, identified
      years ago by pathologists. These aggregosomes affect almost exclusively long
      lived cells (nervous and muscular, macophages). Pigment deposits, such as
      lipofuscines made by the peroxydation of cell membranes, are the most abundant.
      Due to their diverse chemical composition, they cannot be empoyed for a
      scientific classification. Failures of these systems are numerous. They vary not
      according to the chemical nature of the abnormal protein and wastes but the life
      span of the targeted cells and the nature of proteolysis. In this article,
      therefore, the following distinction should be made:--Lysosomal failures. They
      represent hereditary metabolic disorders involving all categories of cells. They
      are characterized by the accumulation of homogeneous material related to the
      underlying disease. Young people are predominantly affected--UPS failures. They
      represent sporadic conditions principally involving long-lived cells. The
      accumulated material is heterogeneous, composed of abnormal proteins and various
      "garbage-like" waste, including pigments. The elderly are predominatly affected,
      suggesting an epigenetic wear and tear process. Hypothetically, most the sporadic
      neurodegenerative diseases, from retinal macular degeneration and its associated
      drusen to Alzheimer's disease, Parkinson's disease may represent fairly good
      examples of the UPS deficit.

PMID- 24313015
TI  - [Placental immunoglobulin transfer].
AB  - Placental immunoglobulin transfer is an active process that involves the FcRn
      receptor and is particularly intense during the last trimester. The transferred
      immunoglobulins reflect the mother's immunological experience, and allow passive
      immunity to the fetus and to the newborn during the first months of life. The
      neonatal protection conferred by placental immunoglobulins transfer is optimized
      by term delivery, normal maternal titers of total immunoglobulins, adequate
      maternal specific immunoglobulin titers, antigen immunogenicity, and a healthy
      placenta. The infant's protection can be reinforced by maternal vaccination,
      especially if there is a threat of life-threatening infantile disease and/or if
      vaccination during the first few months after birth is contraindicated. Better
      knowledge of placental immunoglobulin transfer mechanisms allow a more accurate
      management of biotherapies during pregnancy.

PMID- 24313016
TI  - [Anti-CD 10 maternal-fetal allo-immunisation].
AB  - Maternal-fetal alloimmunisation with antenatal glomerulopathies (FMAIG) is a
      recently described allo-immune disorder that results from the production of
      maternal antibodies which cross the placenta, bind to fetal glomerular podocytes
      and thereby cause renal dysfunction. The pathogenic antibodies are directed
      against CD10/neutral endopeptidase (NEP). The infant's mother is apparently
      healthy but is genetically NEP-deficient, and thus becomes immunized against
      CD10/NEP expressed by placental cells during her first pregnancy. This disease,
      that we have now diagnosed in five families, is the first described organ
      specific disorder due to maternal-fetal allo-immunisation. Because future
      pregnancies in CD10/NEP-immunized mothers are at high risk for the fetus, antigen
      driven therapies aimed at eliminating pathogenic antibodies are urgently needed.
      This will require identification of the pathogenic epitopes born by the antigen.

PMID- 24313017
TI  - [Neonatal lupus: a fetal-maternal immunisation model?].
AB  - Neonatal lupus is due to passive fetal transfer of maternal anti-SSA/Ro and anti
      SSB/La antibodies. The clinical spectrum includes transient skin lesions,
      hematologic and hepatic disorders, and neurological manifestations. Congenital
      heart block (CHB) is the main complication, occurring in the absence of severe
      cardiac malformation. The presence of anti-SSA/Ro antibodies is necessary but not
      sufficient to provoke CHB. The prevalence of CHB in newborns of anti-SSA/Ro
      positive women ranges from 1% to 2%, and the estimated risk of recurrence is 10%
      to 17%. Mothers of newborns with CHB may be asymptomatic or have systemic lupus
      erythematosus or Sjogren's syndrome. The first pathophysiological step is the
      translocation of intracellular SSA/Ro-SSB/La antigens to the surface of apoptotic
      cardiomyocytes, where they can be bound by anti-SSA/Ro antibodies. These antibody
      coated apoptotic cardiocytes are then phagocytosed by macrophages, that in turn
      secrete proinflammatory cytokines such as TNF and TGFbeta. This inflammatory
      cascade results in major alterations of the fibroblast phenotype, ultimately
      leading to fibrosis of the conducting system. While non-cardiac lesions are
      transient, CHB is permanent and is associated with significant morbidity (a
      pacemaker must be implanted in two-thirds of cases) and mortality (estimated at
      16-19%).

PMID- 24313018
TI  - [Foodborne infections in France].
AB  - Prevention and control measures implemented along the human food chain in recent
      decades have been largely successful, as shown by the dramatic decrease in the
      incidence of listeriosis and certain Salmonella serotypes. However, foodborne
      illness continues to be a serious public health threat, due mainly to Salmonella,
      Listeria monocytogenes and Campylobacter. Infections caused by less frequent
      micro-organisms such as shigatoxin-producing E. coli are also a concern, because
      of their serious health consequences and epidemic potential. Surveillance of
      foodborne illness has revealed several important trends, including a substantial
      recent increase in infections by monophasic variants of Salmonella typhimurium, a
      continuing increase in the incidence of Campylobacter infections, and a rapid
      increase in the frequency and antibiotic resistance of Salmonella and
      Campylobacter isolates. These developments highlight the importance of
      epidemiological and microbiological surveillance of humain foodborne infections;
      as well as the need for very close collaboration among all those responsible for
      the surveillance of animal health and the human foodchain.

PMID- 24313019
TI  - [Control of foodborne pathogens in the food industry and the environment: e.g.
      Campylobacter in poultry industry].
AB  - Foodborne zoonoses are not only a major public health concern but also have
      important economic implications, both for the meat industry and for public
      finances. The authors take as an example Campylobacter contamination of the
      environment and of poultry carcasses. Measures that might reduce human exposure
      to Campylobacter are examined for their potential efficacy.

PMID- 24313020
TI  - [Diagnosis and control of human food poisoning outbreaks].
AB  - Medical microbiology laboratories play a key role in the investigation of
      foodborne disease outbreaks. Bacterial pathogens (Salmonella, Escherichia coli,
      Campylobacter, Staphylococcus aureus, Bacillus cereus, Clostridium perfringens,
      etc) have historically been implicated in foodborne illness, while the role of
      viruses (especially Norovirus) appears to have been underestimated. Culture-based
      diagnosis has gradually been complemented, or replaced, by rapid molecular
      methods applied directly to biological samples. These new tools should help to
      reduce the number of outbreaks in which the etiological agent goes unidentified,
      and to improve the exhaustiveness of notifications.

PMID- 24313021
TI  - [Health impact of diesel particles: between myth and reality?].
AB  - Exposure to particulate air pollution produced by traffic, and especially diesel
      particles, is accused of having multiple deleterious effects on human health.
      While some such effects are undeniable, such as the aggravation of respiratory
      allergies, many questions remain as to their impact on mortality, lung cancer and
      cardiovascular events.

PMID- 24313022
TI  - [Women and HIV/AIDS: stormy beginnings].
AB  - Following the transfusion of a young woman with two units of blood infected by
      human immunodeficiency virus (HIV) during a Cesarean section performed at the
      Obstetrics and Gynecology Unit of Port-Royal Hospital in Paris in 1984, the
      author realized the danger that this virus would represent for women and their
      children, at a time when the infection seemed to be confined to homosexuals, drug
      addicts, hemophiliacs and transfusion recipients. He was confronted with a whole
      series of issues, including the rejection of HIV-positive women; the need for
      special precautions in the labor room and operating theater; and the need for
      these patients to be managed in a single center staffed by skilled and willing
      healthcare professionals who could help them decide whether or not to continue
      the pregnancy. The main risks at this time were the onset of life-threatening
      opportunistic infections during pregnancy and HIV transmission to the child
      (estimated at 20% to 30%). Other thorny issues included the case of couples
      wishing to have children when either of the two members was infected, and the
      question of professional confidentiality when an immunocompromised HIV
      seropositive husband stubbornly refused to inform his wife or to use condoms. It
      seemed important to bring these women together, especially those of African
      origin, within a self-help group where they could express themselves openly and
      discuss their difficulties. Screening for HIV antibodies in early pregnancy
      became necessary to permit preventive treatment of mother-child HIV transmission,
      and to inform pediatricians. There was also a need to estimate and monitor the
      seroprevalence of HIV among pregnant women, and this was done by conducting a
      "sentinel" survey that was subsequently taken over by INSERM and the European
      Centre for the Epidemiological Monitoring of AIDS. After listing many other
      issues that were hotly debated over the years, the author describes how, at the
      beginning of the epidemic, new proposals intended to systematically improve the
      lives of these women and their children ran into official procrastination, due to
      the combined pressure of short-sighted doctors, homosexual groups, and a cohort
      of sociologists and philosophers posing as apostles of human rights and
      omnipresent in the media.

PMID- 24313024
TI  - Remarks to hospital medicine town hall. Cincinnati, July 20, 2012.

PMID- 24313023
TI  - The Strategic Planning Committee report: the first step in a journey to recognize
      pediatric hospital medicine as a distinct discipline.

PMID- 24313025
TI  - Improved documentation and care planning with an asthma-specific history and
      physical.
AB  - OBJECTIVE: The objective was to determine the effect of an electronic asthma
      specific inpatient history and physical (H&P) template on documented history and
      improvements in care plans. METHODS: This was a before-after comparison of
      history and care plan documentation following implementation of a new H&P
      template. The template was implemented in May 2011. A retrospective review of the
      electronic health record was completed for 304 consecutive patients (2-16 years
      of age) admitted for asthma June to September 2010 and 242 admitted June to
      September 2011. Elements reviewed included asthma severity classification,
      utilization history (previous oral steroids, emergency visits, hospitalizations,
      intensive care admissions, and intubations), and environmental history (exposure
      to cockroaches, rodents, and mold). Assessed changes in care plans included
      social work or asthma-related subspecialty consult and change in controller
      medications. Patients from 2011 were compared with those from 2010 by using ttest
      and chi2 statistics with adjustment for confounders by use of logistic
      regression. Interrupted time-series analyses assessed variability in
      documentation over time. RESULTS: In 2011, the new H&P template was used in 74%
      of encounters. Compared with patients seen preimplementation, documentation in
      those seen after implementation was more likely to include severity
      classification (71% vs 44%; P < .0001), complete utilization history (73% vs 12%;
      P < .0001), and environmental history (66% v. 2%; P < .0001). Documentation
      became more consistent over time. Changes in care planning were also more common
      after implementation (63% vs 49%; P = .0006). CONCLUSIONS: A structured H&P
      template for asthma led to more complete and less variable documentation of
      important history and likely led to enhancements in care plans.

PMID- 24313026
TI  - Validity of respiratory scores in bronchiolitis.
AB  - OBJECTIVE: The primary objective of this study was to establish the validity and
      reliability of 2 respiratory scores, the Respiratory Distress Assessment
      Instrument (RDAI) and the Children's Hospital of Wisconsin Respiratory Score
      (CHWRS), in bronchiolitis. A secondary objective was to identify the respiratory
      score components that most determine overall respiratory status. METHODS: This
      was a prospective cohort study in infants aged < 1 year seen at Children's
      Hospital of Wisconsin for bronchiolitis. We evaluated: (1) discriminative
      validity (the score's ability to discriminate between 2 different outcomes) of
      the respiratory scores to identify emergency department (ED) disposition by using
      receiver operating characteristic curves; and (2) construct validity (the score's
      ability to measure what it is thought to measure, overall respiratory status) by
      using length of stay (LOS) as a proxy for disease severity and comparing
      correlations between changes in respiratory scores and LOS. Interrater
      reliability was established by using intraclass correlation. The contribution of
      individual respiratory score components to determine ED disposition was studied
      by using multivariate logistic regression. RESULTS: A total of 195 infants were
      included. The area under the receiver operating characteristic curve was 0.68 for
      CHWRS versus 0.51 for RDAI in predicting disposition. There was no correlation
      between initial respiratory scores or change in respiratory scores over the first
      24 hours and LOS. Item analysis revealed that oxygen delivery, subcostal
      retractions, and respiratory rate were independently correlated with ED
      disposition. The CHWRS was more reliable than the RDAI. CONCLUSIONS: The CHWRS
      had modest discriminative validity in predicting ED disposition. Neither the
      CHWRS nor the RDAI had good construct validity. Respiratory rate, oxygen need,
      and presence of retractions were most useful in predicting ED disposition.

PMID- 24313027
TI  - Residency factors that influence pediatric in-training examination score
      improvement.
AB  - OBJECTIVE: The goal of this study was to determine which measurable factors of
      resident training experience contribute to improvement of in-training examination
      (ITE) and certifying examination (CE) scores. METHODS: This is a descriptive
      retrospective study analyzing data from July 2003 through June 2006 at a large
      academic pediatric training program. Pediatric categorical residents beginning
      residency in July 2003 were included. Regression analyses were used to determine
      if the number of admissions performed, core lectures attended, acute care topics
      heard, grand rounds attended, continuity clinic patients encountered, or
      procedures performed correlated with improvement of ITE scores. These factors
      were then analyzed in relation to CE scores. RESULTS: Seventeen residents were
      included in this study. The number of general pediatric admissions was the only
      factor found to correlate with an increase in ITE score (P = .04). Scores for the
      ITE at pediatric levels 1 and 3 were predictive of CE scores. No other factors
      measured were found to influence CE scores. CONCLUSIONS: Although all experiences
      of pediatric residents likely contribute to professional competence, some
      experiences may have more effect on ITE and CE scores. In this study, only
      general pediatric admissions correlated significantly with an improvement in ITE
      scores from year 1 to year 3. Further study is needed to identify which elements
      of the residency experience contribute most to CE success. This would be helpful
      in optimizing residency program structure and curriculum within the limitations
      of duty hour regulations.

PMID- 24313028
TI  - Neonatal bilirubin triage with transcutaneous meters: when is a blood draw
      necessary?
AB  - OBJECTIVE: To find the optimal transcutaneous bilirubin (TcB) screening level in
      term neonates that minimizes the discomfort of phlebotomy, while protecting the
      child from harm and controlling costs. METHODS: All available TcB and total serum
      bilirubin (TSB) measurements taken between 27 and 51 hours of life from a cohort
      of term newborns were analyzed in a retrospective chart review. TcB cutoffs
      between 6 and 12 mg/dL were evaluated for their negative predictive values (NPVs)
      for high risk (HR) and for the combination of high-intermediate risk and HR on
      the Bhutani TSB risk nomogram. RESULTS: One thousand seventy-one full-term
      newborns were entered into the study. Of 601 newborns with TcB < 7 mg/dL, none
      were HR by TSB. Of newborns with a TcB of < 8 mg/dL, 1 in 759 was HR. The NPVs
      for screening levels of 7 and 8 mg/dL were of 100% and 99.9%, respectively, for
      HR and 99% and 97.60%, respectively, for high-intermediate/HR. A cutoff at 12
      mg/dL had NPVs of 99.3% for HR, with 7 neonates, and 92.7% for high
      intermediate/HR, with 76 infants of 1041. CONCLUSIONS: In our center, term
      infants with a TcB of < 8 mg/dL may be safely discharged without a follow-up TSB,
      with the understanding that -1/1000 infants may be at HR for developing severe
      hyperbilirubinemia. Practices with universal follow-up may safely choose cutoffs
      up to 12 mg/dL. An institution's degree of comfort and confidence in follow-up of
      the newborn cohort will guide the choice of an appropriate TcB cutoff requiring a
      TSB.

PMID- 24313029
TI  - Effect of focused debriefing on team communication skills.
AB  - BACKGROUND AND OBJECTIVE: Community hospitals often lack tertiary care support
      such as pediatric intensivists and anesthesiologists. Resuscitation of critically
      ill and injured children in community hospitals requires a well-coordinated team
      effort, because good team performance improves quality of care. The lack of
      subspecialty support makes team coordination and communication more imperative
      yet much more challenging. This study sought to determine if the addition of a
      defined focused post-mock code debriefing session improved communication skills
      among team members in a community pediatric emergency department. METHODS: Twenty
      two volunteer members of the pediatric emergency and respiratory therapy
      departments at Medstar Franklin Square Medical Center took part in monthly
      simulated resuscitations for 3 consecutive months. After each simulation,
      participants answered an 18-item survey on observed communication among their
      team members. Members then participated in a 30-minute debriefing session in
      which they reflected on their own communication skills. A video taping of the
      resuscitation was later scored by one of the investigators by using a rubric
      designed by the investigators. Descriptive statistics were calculated for both
      the participant survey and the team communication indicator scores. Paired-sample
      Wilcoxon signed rank test examined the difference in the scores between each of 3
      sessions. RESULTS: The mean scores by investigator-scored video recordings of the
      teams' mock resuscitation by session showed overall team communication improved
      between sessions 1 and 3 for all communication areas (P = .03), with significant
      improvement in 4 of 9 communication areas by the third session. All team members
      improved communication skills as well, with the greatest improvement by the
      clinical multifunctional technicians. CONCLUSIONS: Communication skills improve
      with the addition of focused debriefing sessions after mock codes as perceived by
      participants during debriefing sessions and evidenced by investigator-scored
      video recordings of resuscitations.

PMID- 24313030
TI  - Resident perceptions of autonomy in a complex tertiary care environment improve
      when supervised by hospitalists.
AB  - BACKGROUND AND OBJECTIVE: Increasingly, academic hospitals have adopted
      hospitalist-based systems of inpatient pediatric care. Some studies comparing
      hospitalists with other attending physicians have suggested trainees are more
      satisfied with education from hospitalists. However, there are published concerns
      that the increased presence of hospitalists may reduce residents' autonomy. The
      objective of the current study was to evaluate pediatric residents' perceptions
      of their own autonomy after a broad ward restructuring to hospitalist-led teams.
      METHODS: We analyzed data from standardized attending evaluations before and
      after a pediatric ward restructuring at an academic tertiary care hospital.
      Provision of most inpatient pediatric care changed from subspecialist-led teams
      to hospitalist-led teams. Numerical scores from evaluations before and after the
      restructuring were compared quantitatively. Comments from the evaluations were
      analyzed qualitatively to identify key themes. RESULTS: Before the restructuring,
      there were 65 evaluations of 5 hospitalists and 602 evaluations of 32
      subspecialists. After the restructuring, there were 188 evaluations of 8
      hospitalists. Hospitalists were rated significantly higher on all teaching
      attributes compared with all attending physicians before the restructuring. The
      attending role in promoting autonomy was mentioned infrequently and reflected
      residents' perceived lack of autonomy before the restructuring. The primary theme
      after the restructuring was autonomy, specifically emphasizing resident
      leadership and decision-making and the appropriate balance of resident autonomy
      and supervision. CONCLUSIONS: Although patient complexity was unchanged, a
      comparison of numerical ratings and resident comments before and after the
      restructuring indicates that hospitalists lead teams differently from
      subspecialists, with more emphasis on resident decision-making and autonomy.

PMID- 24313031
TI  - La Crosse viral infection in hospitalized pediatric patients in Western North
      Carolina.
AB  - OBJECTIVE: La Crosse infection, caused by a rare mosquito-transmitted virus, is
      endemic in Western North Carolina. Given the large number of cases at our
      institution, our goal was to describe the presentation, management, and clinical
      course for pediatric patients with this disease. METHODS: We retrospectively
      reviewed medical records from pediatric patients with antibody-confirmed La
      Crosse infection admitted to Mission Hospital July 2004 through August 2009.
      Demographics, clinical characteristics, management methods, length of hospital
      stay, and complications were analyzed. Regression analysis was used to assess
      relationships between presentation and clinical course. RESULTS: Forty-seven
      pediatric patients were identified with antibody-confirmed La Crosse infection.
      Seventy percent were male, and the median age was 8 years. Admission signs and
      symptoms included fever (43%), headache (94%), vomiting (78%), altered mental
      status (58%), and seizures (61%). All patients had pleocytosis on cerebrospinal
      fluid studies (range 10-1063 cells/mm3). Median length of stay was 5 days.
      Seizure at admission was associated with an increased length of stay (2.4
      additional days, 95% confidence interval 0.7-4.1). Eighteen patients (38%)
      received intensive care, 7 (19%) received parenteral or enteral (via nasogastric
      tube) nutrition, and 4 (9%) received mechanical ventilation. No statistically
      significant associations between presenting signs and symptoms and complications
      were found. Treatments included antibiotics (87%), antiviral medication (55%),
      seizure prophylaxis (47%), and isotonic fluids (98%). CONCLUSIONS: Our data
      reflect few indicators to predict clinical course during hospital stay.
      Management strategies should include attention to development of seizure activity
      and preventive measures for syndrome of inappropriate antidiuretic hormone.

PMID- 24313032
TI  - Sepsis due to superinfected varicella? A case of a challenging rash.

PMID- 24313033
TI  - Pediatric head trauma: abuse or not?
AB  - Your pager sounds at 3 am. You're called to admit a 4-month-old infant who
      sustained a temporal skull fracture. As the overnight pediatric hospitalist at a
      community hospital, you're asked to admit this child to observation. The fall was
      unwitnessed and the floor is hardwood. He vomited twice afterward. Head computed
      tomography scan reveals no additional intracranial injury apart from the skull
      fracture. A skeletal survey reveals no additional injuries. On examination, you
      see bruising of the area. The child is sleepy but neurologically intact. The
      emergency department has called local child protective services, and you wonder
      what you will tell them when they ask your opinion, especially when the family
      has no explanation for what happened.

PMID- 24313034
TI  - Physician attire: a scholarly look.

PMID- 24313035
TI  - The United Nations political declaration on noncommunicable diseases: are
      countries of the Eastern Mediterranean Region ready to respond?

PMID- 24313036
TI  - Physical activity and perceived barriers among high-school students in Muscat,
      Oman.
AB  - A cross-sectional survey was conducted in March 2011 to study the patterns and
      determinants of physical activity among 439 secondary-school students in Muscat
      governorate based on a self-administered questionnaire. Half of the students
      (52.9%) were enrolled in physical education classes and 95.9% reported after
      school physical activities. The recommended level of physical activity (> or =
      1680 MET minutes/week) was met by 23.9% of students, being significantly lower
      among girls (9.8%) than boys (38.8%). More girls were in the stages of pre
      contemplation (5.8%) and contemplation (26.7%) of adopting exercise while more
      boys were in the action (15.4%) and maintenance stages (36.0%). Girls reported
      significantly more barriers to exercise, related to lack of energy, interest in
      other activities, lack of encouragement, worries about looks, and time
      constraints from academic responsibilities and family obligations. The full model
      logistic regression revealed that boys, 11th-grade students and attempts to
      regulate weight significantly predicted physical activity meeting the recommended
      levels.

PMID- 24313037
TI  - Epidemiology of autistic disorder in Bahrain: prevalence and obstetric and
      familial characteristics.
AB  - European and North American studies show that the prevalence of autistic disorder
      is inccreasing. This study was performed to identify the prevalence of autistic
      disorder in Bahrain, and determine some of the demographic and family
      characteristics. Using a case-control design, 100 children who received a
      diagnosis of autistic disorder according to DSM-IV-TR during the period 2000-2010
      were selected. An equal numberofcontrols who had received a diagnosis of
      nocturnal enuresis and no psychopathology were selected, matched for sex and age
      group. The prevalence of autistic disorder was estimated as 4.3 per 10,000
      population, with a male:female sex ratio of 4:1. Significantly more cases than
      controls were delivered by caesarean section and had mothers who suffered
      prenatal complications. The prevalence estimate in Bahrain is comparable to
      previous reports using similar methods. Obstetric complications and caesarean
      section delivery may be associated with autistic disorder.

PMID- 24313038
TI  - Comparison of maternal characteristics in low birth weight and normal birth
      weight infants.
AB  - Low birth weight is a key determinant in the risk of morbidity and mortality in
      the neonatal period and during childhood. This unmatched case-control study in
      Hamadan, Islamic Republic of Iran, compared the characteristics of mothers of low
      and normal-birth-weight infants. Maternal sociodemographic data, pregnancy
      history, anthropometric data and cord plasma zinc level were collected from 134
      mothers of low-birth-weight infants and 134 mothers of normal infants at the time
      of delivery. Significant differences in maternal characteristics namely gravida,
      parity, body mass index, maternal weight gain during pregnancy and plasma cord
      blood zinc were found between low- and normal-birth-weight infants. There were no
      significant differences in maternal age, maternal education, maternal occupation,
      family income, previous abortion, previous preterm labour, birth Iinterval, type
      of clinic and place of residence between the 2 groups.

PMID- 24313039
TI  - Users of withdrawal method in the Islamic Republic of Iran: are they intending to
      use oral contraceptives? Applying the theory of planned behaviour.
AB  - Many couples in the Islamic Republic of Iran rely on coital withdrawal for
      contraception. The purpose of this cross-sectional study was to use the theory of
      planned behaviour to explore factors that influence withdrawal users' intent to
      switch to oral contraception (OC). Participants were 336 sexually active, married
      women, who were current users of withdrawal and were recruited from 5 public
      family planning clinics in Tehran. A questionnair included measures of the theory
      of planned behaviour: attitude (behavioural beliefs, outcome evaluations),
      subjective norms (normative beliefs, motivation to comply), perceived behaviour
      control, past behaviour and behavioural intention. Linear regression analyses
      showed that past behaviour, perceived behaviour control, attitude and subjective
      norms accounted for the highest percentage of total variance observed for
      intention to use OC (36%). Beliefs-based family planning education and
      counsellingshould to be designed for users of the withdrawal method.

PMID- 24313040
TI  - Key role players in health care quality: who are they and what do they think? An
      experience from Saudi Arabia.
AB  - The aim of this study in Medina city in 2009 was to identify key role players who
      influence the healthcare system and to assess their views regarding the
      improvement of the quality of health care in Saudi Arabia. In a qualitative,
      cross-sectional study data were collected from focus group discussions and
      analysed using a content analysis approach. Key role players were chosen based on
      their previous experience in providing feedback in health care-related areas:
      representatives from organizations, interest groups, departments, the media,
      other governmental organizations and members of the public who actively worked
      with the Department of Health. The topics discussed were: health and community;
      health and media; planning for health; female staff views; role of the private
      health sector; and the role of other governmental agencies. The discussions
      highlighted the importance of improvement of health facility infrastructure, the
      implementation of staff training and education, the initiation of quality
      assurance and safety standards and the extension of the scope of primary care and
      community health educational programmes.

PMID- 24313041
TI  - Health-care professionals' perceptions and expectations of pharmacists' role in
      the emergency department, United Arab Emirates.
AB  - The objective of this study was to assess health-care professionals' attitudes
      and perceptions towards the value of certain pharmacist functions in the
      emergency department (ED). The study was conducted among 396 physicians, nurses
      and other professionals in 4 government hospitals and 10 private hospitals in
      Dubai. While 83.6% of respondents reported that pharmacy services were available
      in the ED only 30.7% had a permanent clinical pharmacist working there. A
      majority (75.7%) agreed that the availability of clinical pharmacists in the ED
      would improve quality of care. On the role of clinical pharmacists in the
      medication review process, 45.0% of respondents favoured the review of only high
      risk medication orders in the ED. The study found favourable views towards a role
      for clinical pharmacists in the ED for assuring appropriate medicine prescribing
      and administration, monitoring patient adherence, providing drug information
      consultation and monitoring patient responses and treatment outcome.

PMID- 24313042
TI  - Compliance with the guidelines of prescription writing in a central hospital in
      the West Bank.
AB  - This retrospective, cross-sectional study was carried out to evaluate the quality
      of 2208 outpatient prescriptions in a central hospital in the West Bank,
      Palestine. The physicians' handwriting was poorly readable or illegible in one
      third of the prescriptions. The prescriber's name and signature and patient's
      name were mentioned in almost all orders whereas the patient's age was stated in
      54.9%. The vast majority of physicians (95.5%) prescribed drugs using their trade
      (brand) names. Drug strength, quantity and dose/frequency were stated in 61.1%,
      76% and 73.8% of prescriptions respectively. Only 33 prescriptions (1.5%)
      contained full directions for use for all drugs. Correlation analysis revealed
      that the presence of certain prescription elements was statistically
      significantly associated with the clinic of origin and the number of drugs
      prescribed. The overall poor legibility and incompleteness of the prescriptions
      is of concern.

PMID- 24313043
TI  - What do we need to eradicate rubella in the Islamic Republic of Iran?
AB  - To evaluate the need for congenital rubella syndrome prevention in our national
      health programme we aimed to determine the rate of anti-rubella positivity in
      umbilical cord blood samples 8 years after measles-rubella mass vaccination in
      the Islamic Republic of Iran. In a cross-sectional study we tested umbilical cord
      blood samples for anti-rubella IgG and IgM by ELISA in 154 deliveries at a
      university hospital in Tehran. Overall 72.7% of umbilical cord blood samples were
      positive for anti-rubella lgG and 27.3% were negative. All of the samples were
      negative for anti-rubella IgM. In the samples with a history of mothers' rubella
      vaccination, only 87.5% were positive for anti-rubella IgG. The results suggest
      the need for another mass vaccination for rubella in women of child-bearing age
      and continuation of routine vaccination of infants, plus consideration of
      obligatory anti-rubella IgG testing before pregnancy in women who were not
      vaccinated and vaccination of women before marriage.

PMID- 24313044
TI  - Seroprevalence of rubella among pregnant women in Khartoum state, Sudan.
AB  - Rubella vaccine is not included in the Sudanese national immunization programme,
      and data on prevalence of rubella among women of childbearing age are inadequate.
      The objective of this cross-sectional study was to determine the seroprevalence
      of rubella among pregnant women in Khartoum state, Sudan. A total of 500 pregnant
      women who visited 7 antenatal clinics from November 2008 to March 2009 were
      examined for the presence of rubella IgG antibodies using ELISA. Rubella IgG
      antibodies were detected in 95.1% (95% Cl: 93.2%-97.0%) of women. This
      seroprevalence was significantly associated with education level, but not with
      age, residence area, occupation or parity. We presume this high seroprevalence
      indicates a high circulation of wild rubella virus in Khartoum state. Similar
      studies in other Sudanese states would be important for informing a decision to
      introduce rubella vaccine to Sudan.

PMID- 24313045
TI  - National guidelines for outbreak investigation: an evaluation study.
AB  - This paper reports an independent epidemiological study to evaluate the validity
      of the results of an official investigation into an outbreak of gastroenteritis
      at a university campus in Yasuj, central-south Islamic Republic of Iran. The
      official report of the outbreak by the Department for Disease Control at the
      provincial health centre found only 65 cases over a 5-day period, all females,
      living in the student halls of residence. This contrasts with a questionnaire
      survey of 963 students at the same university, which found 395 students (192
      males and 203 females), living in residences and at home, who reported at least 1
      gastrointestinal symptom over a 12-week period. Within this period at least 2
      outbreaks occurred. Such a large discrepancy between the official report and the
      current study suggests that the health services and the public may have been
      misled about the proper response to the outbreak.

PMID- 24313046
TI  - Unusual sex differences in tuberculosis notifications across Pakistan and the
      role of environmental factors.
AB  - In developing countries, only one-third of new tuberculosis cases notified are
      from women. It is not clear whether tuberculosis incidence is lower in women than
      men, or whether notification figures reflect under-detection of tuberculosis in
      women. Pakistan, however, presents an unusual pattern of sex differences in
      tuberculosis notifications. While 2 of the 4 provinces (Sindh and Punjab) report
      more notifications from men (female to male ratios 0.81 and 0.89 respectively in
      2009), the other 2 provinces (Khyber-Pakhtunkhwa and Balochistan) consistently
      report higher numbers of smear-positive tuberculosis notifications from women
      than men (1.37 and 1.40). No other country is known to have such a large
      variation in the sex ratios of notifications across regions. Large variations in
      female to male smear-positive notification ratios in different settings across a
      single country may indicate that environmental factors, rather than endogenous
      biological factors, are important in influencing the observed sex differences in
      tuberculosis notifications.

PMID- 24313047
TI  - Addressing maternal and child health in post-conflict Afghanistan: the way
      forward.
AB  - Afghanistan's maternal and child mortality rates are among the highest in the
      world. The country faces challenges to meet the Millennium Development Goals set
      for 2015 which can be attributed to multiple causes related to accessibility,
      affordability and availability of health-care services. This report addresses the
      challenges in strengthening maternal and child health care in Afghanistan, as
      well discussing the areas to be prioritized. In order to ensure sound maternal
      and child health care in Afghanistan, policy-makers must prioritize monitoring
      and surveillance systems, integrating maternal and child health care with rights
      based family planning methods, building human resources, offering incentives
      (such as the provision of a conditional cash transfer to women) and promoting
      action-oriented, community-based interventions. On a wider scale, the focus must
      be to improve the health infrastructure, organizing international collaboration
      and expanding sources of funding.

PMID- 24313048
TI  - [General internists and biomarkers].

PMID- 24313049
TI  - [Biomarkers in clinical immunology].
AB  - In a current perspective of individualized medicine, biomarkers appear as a
      simple and readily available aid to assist clinicians in the identification and
      monitoring of diseases whose diagnosis is difficult. Basically, we know the
      limited performance of medical history and of clinical examination; therefore,
      the use of laboratory tests is often seen as the panacea to solve the clinical
      enigma. The purpose of this article is to analyze a few biomarkers commonly
      processed in the immunology laboratory (AAN, ANCA, anti-tTG, rheumatoid factor
      and anti-CCP) and to review the principle, the usefulness and the performance of
      these tests in specific clinical situations. We will see that, far from
      supplanting history and physical examination, these immunological biomarkers take
      their full value as a supplement to clinical information!

PMID- 24313050
TI  - [Biomarkers associated with dyspnea and chest pain: which cinical utility?].
AB  - Dyspnea and chest pain are typical reasons for consultations. biomarkers (CRP,
      procalcitonin, NT-proBNP, troponins, D-dimers) can have an interest for the
      diagnosis, the prognosis and the follow-up of several pathologies. There are
      however numerous pitfalls and limitations between the discovery of a biomarker
      and the utility in clinical practice. It is essential to always estimate a pre
      test probability based on an attentive history and a careful physical
      examination, to know the intrinsic and extrinsic qualities of a test, and to
      determine a threshold of care. A biomarker should be used only if it modifies the
      patient's care and if it brings him a benefit compared to the patient who has no
      biomarker.

PMID- 24313051
TI  - [Complete blood counts: new parameters].
AB  - Performing a complete blood count analysis is a daily routine necessary for a
      good care of patients. Nowadays, modern blood analyzers provide on top of
      classical blood values, several additional parameters. In this paper, using short
      case presentations, we discuss how to interpret these results and integrate them
      in the clinical context.

PMID- 24313052
TI  - [Dysmetabolic hyperferritinemia: a new target for treatment?].
AB  - Dysmetabolic hyperferritinemia is currently the most frequent cause of elevated
      ferritin levels in the general population. Whether dysmetabolic hyperferritinemia
      is a cause or an effect of insulin resistance is still a matter of debate. Still,
      several findings have been well established: increased iron intake or elevated
      ferritin levels are individual risk factors for diabetes, metabolic syndrome or
      gestational diabetes. When in presence of dysmetabolic hyperferritinemia, a small
      number of randomized controlled trials have suggested that therapeutic measures
      aimed at reducing ferritin levels such as low red meat consumption, deferoxamin
      or therapeutic phlebotomies have shown a beneficial effect on glucose
      homeostasis, lipid profile and impaired hepatic markers observed in non-alcoholic
      steatohepatitis.

PMID- 24313053
TI  - [Old and new inflammatory biomarkers: what utility for general internist?].
AB  - The measure of inflammatory biomarkers such as erythrocyte sedimentation rate,
      CRP and procalcitonin is widely used for diagnostic and prognostic purposes in
      patients with fever or inflammatory syndromes. However, their true diagnostic
      accuracy and usefulness are not well known and are probably overestimated. The
      purpose of this article is to summarize the current evidence about the accuracy
      and usefulness of these tests in different contexts of internal medicine.

PMID- 24313054
TI  - [Conducting ward rounds: a balance between care and teaching].
AB  - Every day, hospital doctors spend time at conducting ward rounds. Rounds are a
      core clinical activity during which doctors interact with patients, synthetise a
      whole set of informations and make many decisions. In addition, rounds can become
      a crucial teaching moment, when a trainee gets supervised by an attending
      physician. However, litterature on the topic of rounds is scarce. This paper
      summarizes the results of the few key studies focusing on ward rounds. The
      results are presented in four sections, each one being dedicated to one of the
      round stakeholders: the trainee or resident, the trainer, the patient and the
      nurse. An emphasis is put on ward rounds involving both a trainee and a trainer,
      since such rounds always mean striking a balance between care and teaching.

PMID- 24313055
TI  - [We will leave you the care of...].

PMID- 24313056
TI  - [Mad cow: the new and problematic British epidemiologic situation].

PMID- 24313057
TI  - [Would the woman become the owner of her body?].

PMID- 24313058
TI  - [The miracles of etiopathy which cures the Parisians].

PMID- 24313059
TI  - [Politics of non-prevention].

PMID- 24313060
TI  - [Frequency and distributions of cervical lymph node metastases in oropharyngeal
      squamous cell carcinoma].
AB  - OBJECTIVES: To examine the frequency and distribution of cervical lymph node
      metastases in oropharyngeal squamous cell carcinoma (SCC) and the necessities of
      prophylactic treatment of the neck. METHODOLOGY: We conducted a retrospective
      study of 242 patients with SCC of the oropharynx treated by surgery as the
      initial therapy at the National Cancer Center East Hospital from 1994 to 2008,
      excluding 53 patients who had local recurrences and 9 patients who had previously
      undergone neck dissection for metastasis from an unknown primary. We defined
      "potential lymph node metastases" as cases pathologically positive for lymph node
      metastases and/or secondary lymph node metastases and analyzed the necessity of
      prophylactic neck dissection for cases clinically negative for cervical
      metastases. RESULTS: One hundred and eighty patients (148 males, 32 females) were
      included. The median age was 62 years (35 to 78). The clinical stages were Stage
      I in 20 patients, Stage II in 36 patients, Stage III in 39 patients, and Stage IV
      in 85 patients. In the ipsilateral neck of 70 patients at clinical stage N0, 15
      patients (21.4%) were positive for potential lymph node metastases. There was no
      significant difference in the frequency of metastases by subsite. In terms of T
      classification, the positivity rates were 5.0% in patients at T1, 19.4% at T2,
      44.4% at T3, and 60.0% at T4. In the contralateral neck of 70 patients at
      clinical stage N0, only 2 patients (2.9%) were positive for potential lymph node
      metastases. In the contralateral neck of 93 patients at clinical stage N1, N2a,
      or N2b (i.e., unilateral lymph node swelling), 16 patients (17.2%) were positive
      for potential lymph node metastases. The positivity rates by subsite were higher
      in patients with anterior, superior and posterior wall cancer than those with
      lateral wall cancer. CONCLUSIONS: In the ipsilateral neck of patients at clinical
      stage N0, prophylactic neck dissection is not necessary for patients at T1 but
      necessary for those at T3 or T4. In the contralateral neck of such patients,
      prophylactic neck dissection is not recommended. In the contralateral neck of
      patients with unilateral lymph node swelling, prophylactic neck dissection is
      recommended for patients with anterior, superior or posterior wall cancer.

PMID- 24313061
TI  - [An attempt to evaluate postural control with a magnetic motion capture system].
AB  - Measurement of the body sway can be useful in the assessment of the ability to
      maintain posture. It is, however, difficult to quantitatively evaluate the
      chronological changes in the equilibrium function in the elderly. Although it is
      considered that not only sway movement of body center of gravity but also head
      movement should be measured for essential assessment of postural control, few
      methods are suitable for a clinical test. In this study, we investigated the head
      and trunk movement in elderly subjects standing upright, using a magnetic motion
      capture system to substantiate its usefulness. Seven subjects aged 66 to 83 years
      old were instructed to stand with their feet close together on the stabilometer
      with eyes open and then eyes closed for periods of 30 seconds each, while the
      movement of the head, cervix and lumbar region (MH, MC and ML) were monitored
      three-dimensionally with the magnetic motion capture system. The obtained data
      were compared with the movement of the body's center of gravity (MCG). The
      results were as follows: The MH was the largest, followed by MC and ML, and the
      ML trace was similar to that of the MCG. MH, MC, ML and the ratio of the MH to ML
      increased with age, and they were considered to be a valid index for assessment
      of postural control. A magnetic motion capture system, which can record the
      movements of the head, cervix and lumbar region accurately and conveniently, is
      seen as potentially and clinically useful apparatus for evaluation of postural
      control in dizzy patients, especially the elderly.

PMID- 24313062
TI  - [A case of angioimmunoblastic T-cell lymphoma arising in the cervical region].
AB  - A case of angioimmmunoblastic T-cell lymphoma (AITL) is herein reported. The
      patient was a 33-year-old female who presented with a tumor arising in the rear
      of the left lobe of the thyroid. Total removal of the tumor was easily
      undertaken. Histopathological examinations with Anti-CD3, CD10, CD45RO positive
      stainings confirmed the diagnosis of AITL. After the determination of stage
      categories with IA, 3 courses of chemotherapy with CHOP were administered
      followed by X-ray irradiation of the cervix with 40 Gy. Thereafter close follow
      up has not revealed any recurrence. Serum levels of soluble IL-2 receptor (sIL
      2R) gradually decreased according to the round of treatments. AITL is a rare
      clinical entity included in 1.2-2.5% of non-Hodgkin's lymphomas, which has not at
      all been reported in the issues concerning otorhinolaryngology. Clinical symptoms
      and findings include general lymphoadenopathy, hepatosplenomegaly, skin rash,
      anemia and hypergannmagloburinemia. Diagnosis is determined by histopathological,
      immunohistochemical and clonality examination. Chemotherapy regimens using multi
      agents combined with anthracycline i.e. CHOP have been playing the fundamental
      role in the therapeutic paradigm, but because of the poorer survival of 20-50% at
      the 5-year point, AITL is classified as a high-grade malignancy.

PMID- 24313063
TI  - [Repeated syncope episodes caused by intractable hiccups; a case report].
AB  - A 66-year-old man visited our hospital with a chief complaint of a sore throat.
      On examination, the pharyngeal and laryngeal mucosa was reddish and localized
      mucosal erosion was present on the left side. Based on an initial diagnosis of
      acute pharyngitis caused by bacteriological infection or mycotic infection,
      treatment with antibacterial and antimycotic agents was initiated. However, the
      patient's sore throat gradually worsened and he developed intractable hiccups.
      Intravenous steroids were given for the treatment of the severe sore throat, and
      this symptom was gradually alleviated. However, the intractable hiccups
      persisted. In addition, the patient began to have convulsive syncope episodes and
      was subsequently admitted to our hospital. Further examination revealed that the
      syncope episodes were linked to the hiccups. To treat the hiccups, baclofen and
      Chinese medicine were prescribed, and the convulsive syncope episodes disappeared
      immediately. The patient's hiccups also improved and disappeared six days
      thereafter. Based on this clinical evidence, we concluded that the hiccups were
      caused by pharyngitis, resulting in the stimulation of the glossopharyngeal
      nerve, while the convulsive syncope episodes were a type of situational syncope
      related to hiccups.

PMID- 24313064
TI  - [Our experience with percutaneous trans-esophageal gastrotubing (PTEG)].
AB  - Percutaneous endoscopic gastrostomy (PEG) has been generally used as a long-term
      enteral nutrition route for patients in whom oral intake is impossible.
      Percutaneous trans-esophageal gastrotubing (PTEG) is useful for the patients in
      whom PEG insertion has not been indicated. A gastroenterologist usually performs
      PTEG in Japan, but in our hospital otolaryngologists have performed this
      procedure. From 2006 to 2012, we experienced 9 patients who underwent PTEG
      insertion without a life-threatening adverse event. An otolaryngologist who is
      accustomed to the cervical procedures can safely perform PTEG insertion.

PMID- 24313065
TI  - [Health education: the poor relation of health policy?].

PMID- 24313066
TI  - [Issues and practices in health education].

PMID- 24313067
TI  - [The ethical dimensions of health education, or the limits of beneficence].
AB  - Ethical issues have only recently emerged as a topic of debate in health
      education. Until recently, health education was seen as "beneficent" by nature
      and as designed to improve well-being and quality of life. Traditionally, the
      purpose of health education was to promote behavior change. The idea of intruding
      into people's private lives raises the question of the objectives and methods of
      health education. The principles underlying ethical reflection--beneficence, non
      malfeasance, autonomy and social justice--provide a basis for identifying a
      number of problems or abuses. Traditionally, people have tended to be seen as
      implicitly responsible for their own behavior, a view based on a moralistic,
      guilt-inducing and didactic approach to health and health behavior. The
      assumption is that these infringements affect the identity and dignity of
      persons. In addition, imposing standards and norms of behavior defined by others
      amounts to undermining or denying the autonomy of individuals. Finally,
      traditional health education approaches, and in particular communication
      campaigns, may contribute to the improvement of health, but it is at the cost of
      increased inequalities. To conclude, ethics is both a statement of values and a
      method or process. Ethics needs to be debated and discussed in a democratic
      forum. It is up to citizens, not experts, to establish the link between means and
      ends. Health promotion has resulted in a shift in perspective--a shift that has
      provided protection against ethical lapses and violations. This paper argues that
      health education must create the conditions of autonomy by focusing first on
      environmental factors and inequalities.

PMID- 24313068
TI  - [The current state of health education in France: cause or consequence of the
      lack of political commitment?].
AB  - Fifteen years ago, the limited resources allocated to health education in France
      were due to a lack of legitimacy compounded by a lack of professional
      recognition, in addition to a lack of research and a state of methodological
      anarchy. A national health education program was launched in 2001 to address this
      issue. However, the program was only partially implemented. Recent reforms have
      strengthened the national structure and promoted health communication campaigns.
      Therapeutic patient education has also been legally recognized. However, the
      resources allocated to community health education have steadily declined, despite
      efforts to promote training, quality improvement and rationalization. Health
      promotion--without which health education activities cannot be developed--is
      still struggling to gain recognition. Investments in health promotion have not
      increased as a result of the demonstrable effectiveness and professionalization
      of the sector and of the quality of its services. Indeed, the reverse may be
      true. In other words, investments in this area may promote the development of
      research, assessment and quality, while also highlighting the impact on the
      determinants of health and well-being. Ultimately, there is evidence to suggest
      that investments in this area can help to reduce premature mortality rates and
      the number of preventable deaths.

PMID- 24313069
TI  - [Health education in the French Regional Health Agencies in 2012: observations
      and analysis].
AB  - This paper examines the role of health education in the French Agences regionales
      de sante (ARS, Regional Health Agencies) in 2012. A survey was conducted among
      public health managers working in the ARS. Most of the participants reported that
      health education plays an important role in their agency, notably through their
      regional health plan and the activities of the organizations responsible for
      promoting democracy in health care. This is also true of the links with the
      Institut national de prevention et d'education pour la sante (INPES, the National
      Institute for Health Prevention and Education) and the network of Instances
      regionales d'education et de promotion de la sante (IREPS, the Regional
      Authorities for Health Education and Promotion). However, the answers to the open
      ended questions and the results of the interviews suggest that these results must
      be interpreted with caution. The study focuses on a number of factors that must
      be taken into account when considering the results of the quantitative analysis.
      These factors include: the subjective (or interpretive) dimension of the term
      "health education" emphasized by many of the participants (a term involving an
      emphasis on either health promotion or preventive medicine); the limited emphasis
      on health education in the ARS (beyond therapeutic patient education) compared to
      other issues such as health monitoring and security, health care and medico
      social problems; the limited resources allocated to health education and the
      bleak budget outlook; the relationships with the main operators; and the need to
      develop, promote and apply knowledge of good practice. Finally, the study shows
      that the role of health education is dependent on individuals' willingness to
      promote it and, in particular, on the commitment of ARS managers.

PMID- 24313070
TI  - [Health promotion at last? Trends in French health education over the past
      decade].
AB  - Major legislative, structural and organizational changes have had a significant
      impact on public health in France over the past decade. This paper examines the
      effects of these changes in terms of the development of health education over the
      same period. Six significant trends were identified: the development of research
      in health education, the emphasis on health education as a strategy for reducing
      health and social inequalities, the emergence of health education as a field of
      intervention, the emergence of therapeutic patient education, the unprecedented
      economic difficulties of health education associations, and the changing
      perception of health education among public health authorities. The embeddedness
      of health education in health promotion remains vital since it provides the basis
      for developing the full potential of health education as part of a cross-sector
      approach, in combination with a range of other strategies aimed at broadening the
      scope of intervention.

PMID- 24313071
TI  - [From behavior change to the improvement of living conditions. Toward ethical and
      effective health education].
AB  - Health education is the basis of all public health policies and programs.
      However, the fundamental principles of health education are often misunderstood
      by decision-makers and other key social actors, who often overestimate the impact
      of health education or overlook its benefits. This paper examines the benefits of
      health education from the point of view of preventive measures and health
      promotion measures. The paper highlights the tendency to restrict the theoretical
      perspectives underlying the development of programs to an examination of intra
      individual factors, thus overlooking the constraining effects of the physical and
      social environment on health decisions. The paper concludes by recommending a
      form of health education aimed at individual and collective emancipation and by
      calling for the implementation of population health strategies based on tried and
      tested theoretical models of health promotion.

PMID- 24313072
TI  - [Health education, patient education and health promotion: educational methods
      and strategies].
AB  - The purpose of this paper is to help public health actors with an interest in
      health promotion and health care professionals involved in therapeutic education
      to develop and implement an educational strategy consistent with their vision of
      health and health care. First, we show that the Ottawa Charter for Health
      Promotion and the French Charter for Popular Education share common values.
      Second, an examination of the career and work of Paulo Freire, of Ira Shor's
      pedagogical model and of the person-centered approach of Carl Rogers shows how
      the work of educational practitioners, researchers and theorists can help health
      professionals to implement a truly "health-promoting" or "therapeutic"
      educational strategy. The paper identifies a number of problems facing health
      care professionals who become involved in education without reflecting on the
      values underlying the pedagogical models they use.

PMID- 24313073
TI  - [Health education in Quebec: developments over the past decade and current
      prospects].
AB  - This study examines the views of five university professors in the province of
      Quebec on recent trends and developments in health education, the relative
      importance of health education as a health promotion strategy, and future
      prospects. Interviews were conducted and the participants were asked to validate
      the findings. Despite minor differences, the participants were found to have
      similar views on health education. The interviews also pointed to a significant
      emphasis on recent developments in our understanding of the factors influencing
      health behaviors and the theoretical foundations underlying processes of change.
      However, much remains to be done to put this knowledge into practice. In Quebec,
      the field of health education has involved an increasingly diverse range of
      actors in recent years, although nurses continue to play an important role. Some
      feel that the emphasis on creating supportive environments for health and public
      policies has had a negative impact on the development of health education in
      Quebec. For others, we are witnessing the emergence of a more integrated system
      combining different health promotion strategies. In terms of future prospects,
      some remain pessimistic, emphasizing the potential effects of the current
      economic climate or the potential negative impact of the rise of therapeutic
      education, which may be at the expense of a more systemic approach. Others are
      more optimistic, arguing that the future of health education will be a matter of
      political will and that it will depend on the efforts of stakeholders to promote
      consistent and complementary measures.

PMID- 24313074
TI  - [Will health promotion remain a utopia in a fragmented political system? The case
      of the Wallonia-Brussels Federation].
AB  - In the French Community of Belgium (the Wallonia-Brussels Federation), the
      changing political landscape and the various laws relating to the roles of the
      federal state, communities and regions introduced since 1980 have had a
      significant impact on health policy. Since then, there have been significant
      developments in health education services and activities. In 1997, a government
      decree was issued to promote the concept of health promotion, to reform the
      existing system and to define policy priorities as part of a new five-year plan
      (1998-2003). Significant progress was made during this period as a result of the
      development of a global approach extending beyond the mere analysis of risk
      factors. The second five-year plan (2004-2008), aimed at combining preventive
      medicine and health promotion, resulted in the involvement of a wider range of
      actors and greater cross-sector collaboration. However, the sheer number of
      decision-making levels has been a major obstacle to popular participation and
      consultation. If the question of social and cultural accessibility is not
      seriously addressed, the focus on preventive medicine programs may prove to be
      detrimental to the development of an effective health promotion framework. The
      disconnect between the political vision and the reality of practice has had an
      adverse impact on health promotion. Health promotion professionals have
      repeatedly called for a third five-year plan involving all ministers and aimed at
      developing a cross-sector approach, at addressing the determinants of health, at
      promoting the active participation of local communities and at reducing social
      health inequalities. The concerns of health promotion practitioners were further
      exacerbated by the introduction of an external assessment process initiated by
      the Ministry of Health in 2010. The current concerns over the future of the
      Belgian state, the economic crisis and the impact of spending cuts have increased
      the sense of uncertainty. The upcoming elections provide further incentive for
      health promotion professionals to continue in their efforts to promote effective
      policy responses based on the skills and experience of associations and on
      practice quality.

PMID- 24313075
TI  - [Health education in Latin America in the twenty-first century: a level of
      visibility inversely proportional to practice quality].
AB  - In Latin America, the concept of health education has undergone significant
      changes in recent times, and the object, theory and methods of professional
      practice have been redefined. The purpose of this paper is to examine trends in
      practice, research and training among health education professionals in Latin
      America from the early twentieth century to the present. METHODS: A literature
      review was conducted and a questionnaire was sent to 24 professional
      practitioners in fifteen Latin American countries. RESULTS: The participants
      reported that they had seen a decline of interest in their discipline, its field
      of action and the health education activities implemented at individual and
      collective levels. However, the design of interventions appears to have improved.
      Interventions in this area are based on the results of studies on people's
      perception of and response to risk and vulnerability and on educational
      experiences based on action research that have contributed to reducing
      inequalities and to politicizing the public health debate. CONCLUSION: The
      conceptual and operational frameworks of health promotion and education have
      converged in recent years. Health education has incorporated theoretical and
      methodological frameworks from the field of collective health and from
      anthropology and the social sciences. However, these developments remain
      marginal. Many countries continue to rely on one-directional biomedical
      conceptions of the health education process that downplay the importance of
      structural factors and social organizations.

PMID- 24313076
TI  - [Health education in Brazil: from Paulo Freire to today].
AB  - This paper examines the experience of Brazil in the area of health education
      integrated in popular education movements. More specifically, the paper discusses
      the link between health education and popular education, focusing in particular
      on the work of Paulo Freire. Anti-slavery movements, protest movements against
      social inequalities and the reconstruction of democracy after the end of the
      military dictatorship (1965-1984) provided fertile ground for a dynamic process
      of change--a process illustrated by the creation of the Unified Health System.
      These developments occurred in a context of social change and unrest. Since then,
      other actors and other forms of action have emerged, though creativity and
      popular empowerment remain central to the process of change. However, in popular
      education, nothing is set in stone and new issues have emerged, as Paulo Freire
      had predicted. The point is to recognize that popular education applied to
      health, or rather integrating health, is constantly changing and developing.

PMID- 24313077
TI  - [The relationship between a health education program and its assessment: the
      example of Couleurs Sante].
AB  - Couleurs Sante was a community mobilization program implemented in six areas of
      Brittany, France. The aim of the program was to develop health education projects
      in schools and among children and adolescents with a view to promoting the
      development of psychosocial skills and creating healthy environments. Assessment
      was an integral part of the program, the main aim being to evaluate the
      effectiveness of the program and its transferability to other settings. The
      assessment process was examined in order to determine the impact of the
      assessment on the program and to assess the influence of stakeholders on the
      assessment method. This paper provides an overview of the development of the
      program and the associated assessment process and shows how the assessment
      process has helped to improve the program. The findings highlight the diversity
      of local approaches and strategies, underlining the importance of the varying
      interpretations of the initial framework, the contributions of actors and
      environmental opportunities and constraints. The study also highlights the
      importance of considering the context and the expectations of actors for
      developing a method adapted to the program model and for meeting the needs of
      users.

PMID- 24313078
TI  - [Photolanguage "youth and nutrition": a tool for understanding the meaning of
      eating among youth].
AB  - This paper describes the design and implementation of a tool for examining
      representations of eating practices among youth using group work. The proposed
      method recognizes the complexity of the issues surrounding food and eating among
      young people while setting clear and realistic goals. This means taking into
      account the many determinants of eating behavior and empowering young people to
      control these factors. In doing so, the paper illustrates two fundamental
      principles of health promotion.

PMID- 24313079
TI  - [Health workshops for people with social difficulties offered by the IREPS (Pays
      de la Loire, France): practice and concepts].
AB  - Implemented by the Instance Regionale d'Education et de Promotion de la Sante
      (IREPS, Regional Authority for Health Education and Promotion) in the Pays de la
      Loire region of France, the "ateliers sante avec des personnes en difficultes
      sociales" ("health workshops for people with social difficulties") involve group
      sessions aimed at providing health education. The workshops involve three key
      stages (diagnosis of the situation, preparation for sessions and assessment) and
      are designed to give people control over their health. More than ten years after
      the introduction of the workshop as part of the Programmes Regionaux d'Acces a la
      Prevention et aux Soins (PRAPS, Regional Programs for Access to Prevention and
      Care), this study re-examines the objectives and implementation of the workshops,
      but also focuses on the skills of the professionals responsible for their
      implementation. A qualitative study was conducted using semistructured interviews
      with IREPS professionals, workshop participants and the coordinators of the
      organizations where the workshops are held. In total, twenty-four people were
      interviewed and ten workshop meetings were attended, including a workshop at the
      "Ecole de la Deuxieme Chance" in Nantes. The results demonstrate the importance
      of considering the conditions needed to promote the implementation of the
      workshops while taking into account the demands of practice. Some of the main
      objectives are also examined, as is the need for professionals to combine
      technical and relational skills. The results provide a basis for analyzing the
      health workshops based on the theoretical foundations of health education. Beyond
      these theoretical considerations, the study examines the relationship between the
      workshops and the reduction of social inequalities in health in a context of
      increasing inequality.

PMID- 24313080
TI  - [Health education at the health workshops of Cahors: challenges].
AB  - There have been significant developments in health education over recent years.
      Focusing on France, the purpose of this paper is to examine the role of health
      education in reducing social inequalities based on the example of the Atelier
      sante ville de Cahors (Cahors Health Workshop). The paper addresses the following
      questions: What are the results and outcomes of the workshop? What kind of health
      education issues are at stake in the territorial approach to policy-making in an
      urban context? We examined the methods underlying the health education measures
      taken in the Cahors Health Workshop, which involve project-based approaches and
      the promotion of community health. Health education aimed at improving health is
      central to issues such as listening and speaking, the development of autonomy and
      the responsibilization of urban actors. Based on a rigorous methodology and the
      underlying values, health education in the Cahors Health Workshop places local
      residents, elected representatives and health professionals at the heart of the
      health care process (from the diagnostic process to the assessment process) and
      contributes to the reduction of social inequalities in health while facilitating
      access to information and health care. The goal of health education is to
      encourage individuals to be responsible for their own health in order to empower
      them to make informed choices adapted to the demands of their environment.

PMID- 24313081
TI  - [Promoting sexual and reproductive health as part of an educational program among
      Romani women].
AB  - In 2012, the "Centre d'Accueil, de Soins et d'Orientation" run by Medecins du
      Monde in Bordeaux (France) developed an educational program aimed at promoting
      sexual and reproductive health among Romani women from Bulgaria and Romania. A
      preliminary study was conducted using a qualitative methodology involving focus
      groups and individual interviews. A close relationship was found between the
      participants' cultural beliefs about sexual and reproductive health and their
      precarious living conditions. An analytical framework focusing on representations
      of motherhood and birth control highlighted the resources and constraints shaping
      their attitudes and the challenges they face. The results provide support for a
      recent attempt to promote health among Romani women living in the area. More
      specifically, an educational approach designed to provide support and assistance
      was recently developed to help women find solutions tailored to their needs and
      designed to increase their decision-making abilities. The program also involves
      an advocacy approach. The implementation of the project is further supported by
      an assessment process, which will be followed by a summative evaluation of the
      resulting effects and an assessment of the impact of the program on the
      perception of reproductive health among the local Romani population.

PMID- 24313082
TI  - ["I love my heart": a regional program to reduce cardiovascular risk and health
      inequalities].
AB  - "Je t'aime mon coeur" ("I love you, my heart") is a regional program aimed at
      reducing cardiovascular risk based on a strategy consistent with the Ottawa
      Charter. One of the objectives of the program is to reduce health inequalities
      between the general population and disadvantaged groups with limited access to
      preventive services. Among disadvantaged groups, access to the program appears to
      be related to the activities designed specifically for them and, in particular,
      to the support provided by professionals dedicated to the task. The study also
      shows that the program has had a positive impact on key determinants of health,
      including individual factors (knowledge, perceived self-efficacy, self-esteem,
      etc.) and environmental factors. In addition, the study provides evidence of
      social mobilization and indicates that the targeted populations have responded
      positively to the program. There is also evidence of better coordination between
      professionals from different fields. However, the level of public participation
      in governance remains low, particularly in the steering committee and the
      technical committee. Additional resources are needed to promote the emergence of
      a public group or population actively involved in implementing the program. The
      participation of the general public in the team behind the project should enable
      people to become actors in their own right on a par with other stakeholders.

PMID- 24313083
TI  - [Patient education for diabetic patients in precarious conditions: fostering and
      promoting relationships].
AB  - Meetings between patients and professionals were held with a view to developing
      guidelines for patient education. The participants included ten patients with a
      low socioeconomic status and struggling to control their diabetes, ten health
      professionals dealing with issues in diabetes education and a member of an
      association of diabetic patients. The participants highlighted the importance of
      fostering links between patients, between professionals, and between patients and
      professionals in order to promote involvement and mobilization and to encourage
      the development of a viable long-term education program.

PMID- 24313084
TI  - [Promoting access to health care among deaf and hard of hearing youth: the
      example of the internet training workshops].
AB  - Social inequalities in health remain a major problem in France despite recent
      efforts to improve access to prevention and care. In France, the reduction of
      inequalities involves many actors, including the Instances regionales d'education
      et de promotion de la sante (IREPS, the Regional Authorities for Health Education
      and Promotion). This paper focuses on health education for deaf and hard of
      hearing youth. The educational team responsible for providing health education
      among this population has highlighted the dangers of internet use among deaf and
      hard of hearing youth. The overall objective is to "promote the critical and
      responsible use of the Internet", focusing in particular on social and technical
      skills. The project is a long-term intervention based on the active involvement
      of the educational team and the participating youth. Another objective of the
      project is to enable participants to contribute to online resources. This has
      involved using QR codes to create digital resources. The study found high levels
      of satisfaction among all the participants. These findings provide further
      evidence of the importance of providing health education to deaf and hard of
      hearing people.

PMID- 24313085
TI  - Resource utilization and cost of inserting peripheral intravenous catheters in
      hospitalized children.
AB  - OBJECTIVE: The goal of this study was to measure the costs and difficulty in
      placing peripheral intravenous (IV) catheters in hospitalized children; measures
      of resource utilization. We measured the costs and difficulty in placing
      peripheral intravenous (IV) catheters in hospitalized children. This common
      procedure has implications for the utilization of hospital resources. METHODS:
      This was a prospective, large-scale observational study in 2 southeastern US
      pediatric teaching hospitals evaluating 592 children needing peripheral IV
      catheters in the inpatient setting. The median age was 2.25 years with an age
      range of 2 days to 18 years. Costs were estimated by using directly measured
      staff time and national salary data. Analyses included costs according to patient
      characteristics (age, weight, dehydration, and difficulty of stick attempts), and
      nurse characteristics (experience in years and anticipated difficulty). RESULTS:
      The median cost of the pediatric IV insertions was $41, and 60% of the placements
      were obtained with the first nurse. Seventy-two percent of the children had a
      successful IV insertion in 1 to 2 attempts and accounted for 53% of total costs.
      However, the 28% of children who required > or = 3 IV attempts had a cost range
      of $69 to more than $125, and they consumed 43% of the total IV costs. This
      subset was often < 2 years old or dehydrated (P = .0002). CONCLUSIONS: The
      insertion of peripheral IV catheters in an inpatient setting can be time
      intensive and requires significant skill. Our study suggests that resource
      utilization may improve when nurses and personnel proficient in starting
      peripheral IV catheters are used when the initial nurse has failed to obtain IV
      access. This systems improvement should result in shortened time to
      administration of parenteral therapies, positively improving outcomes and
      lessening length of stay, as well as improving patient/family satisfaction due to
      reduced perceptions of pain.

PMID- 24313086
TI  - Not just a little pinch: first do no harm with pediatric peripheral IV catheters.

PMID- 24313087
TI  - Hospitalization of early preterm, late preterm, and term infants during the first
      year of life by gestational age.
AB  - OBJECTIVES: The goal of this study was to describe hospitalizations of infants
      during the first year of life according to week of gestational age (GA). We
      hypothesized that odds of any hospitalization would generally decrease with
      increasing GA, with late preterm infants experiencing additional increased risk
      of specific hospitalizations, such as hyperbilirubinemia. METHODS: Birth
      certificates for > 6.6 million infants born in California hospitals between 1993
      and 2005 and surviving to discharge were linked to hospital discharge records
      during the first year of life. Odds of any hospitalization and any
      hospitalization for specific diagnoses during the first year of life were
      determined for infants 23 to 44 weeks' GA. Further analysis determined odds of
      any hospitalization within 14, 30, and 90 days of birth discharge, and observed
      odds were compared with expected odds obtained through quadratic modeling.
      RESULTS: Odds of any hospitalization within the first year of life decreased with
      advancing GA, but observed odds of any hospitalization exceeded expected odds for
      35-, 36-, and 37-week GA infants for all time periods after discharge. Odds of
      any hospitalization for hyperbilirubinemia were greatest for infants 33 to 38
      weeks' GA (peak odds ratio at 36 weeks' GA: 2.86 [95% confidence interval: 2.73
      3.00]), and a relative peak in odds of any hospitalization for specific
      infections was observed among infants 33 to 36 weeks' GA. CONCLUSIONS: Odds of
      any hospitalization during the first year of life exceeded expected odds of
      hospitalization for 35-, 36-, and 37-week GA infants. GAs at risk overlapped
      with, but were not identical to, GAs identified as late preterm infants.

PMID- 24313088
TI  - Preventing dehydration-related hospitalizations: a mixed-methods study of
      parents, inpatient attendings, and primary care physicians.
AB  - OBJECTIVE: The goal of this study was to identify the proportion of dehydration
      related ambulatory care-sensitive condition hospitalizations, the reasons why
      these hospitalizations were preventable, and factors associated with
      preventability. METHODS: A cross-sectional survey of primary care providers
      (PCPs), inpatient attending physicians, and parents was conducted in a
      consecutive series of children with ambulatory care-sensitive conditions admitted
      to an urban hospital over 14 months. RESULTS: Eighty-five children were diagnosed
      with dehydration. Their mean age was 1.6 years; most had public (74%) or no (17%)
      insurance, and were nonwhite (91%). The proportion of hospitalizations assessed
      as preventable varied from 12% for agreement among all 3 sources to 45% for any
      source. Parents identified inadequate prevention (50%), poor self-education
      (34%), and poor quality of care (38%) as key factors. PCPs identified parents
      providing insufficient home rehydration (33%), not visiting the clinic (25%), and
      not calling earlier (16%) as reasons. Inpatient attending physicians cited home
      rehydration (40%), delays in seeking care (40%), and lacking a PCP (20%) as
      contributors. Physicians (PCPs and inpatient attending physicians) were more
      likely than parents to describe the admission as inappropriate (75% vs 67% vs 0%;
      P < .01). Parental dissatisfaction with their child's PCP and a history of
      avoiding primary care due to costs or insurance problems were associated with
      significantly higher odds of preventable hospitalization. CONCLUSIONS: Up to 45%
      of dehydration-related hospitalizations may be preventable. Inadequate parental
      education by physicians, insufficient home rehydration, deferring clinic visits,
      insurance and cost barriers, inappropriate admissions, poor quality of care, and
      parental dissatisfaction with PCPs are the reasons that these hospitalizations
      might have been prevented.

PMID- 24313089
TI  - Clinical profile of children requiring early unplanned admission to the PICU.
AB  - OBJECTIVE: The goal of this study was to describe the frequency, characteristics,
      and outcomes of children who require early unplanned admission to the PICU within
      24 hours of hospitalization from the emergency department. METHODS: This study
      was a retrospective audit of 24 months of prospectively collected medical
      emergency team records at a tertiary pediatric hospital in Canada. Our review
      identified 39 hospitalized children who had an activation that resulted in
      unplanned admission to the PICU within 24 hours of admission from the ED.
      RESULTS: Forty-six percent of the study subjects were infants aged < 1 year, and
      64% were male. Respiratory complaints were the most common reason for
      hospitalization (59%). Preexisting medical conditions (51%), abnormal respiratory
      rates (46%), abnormal heart rates (33%), abnormal blood gas values (49%), high
      supplemental oxygen requirement (23%), and treatment with nebulized medications
      (46%), intravenous fluids (33%), and antibiotics (33%) were common. The median
      time to medical emergency team activation was 9.4 hours (interquartile range: 4.4
      14.5). Nearly one-half (49%) of the patients required a significant intervention
      after admission to the PICU, with a mean length of stay of 3.4 days and a
      mortality rate of 50/%. CONCLUSIONS: Male subjects, infants aged < 1 year, and
      children with respiratory complaints accounted for a large proportion of children
      requiring early unplanned admission to the PICU within 24 hours of
      hospitalization from the ED. Further studies are required to determine which
      factors are associated with deterioration after hospitalization.

PMID- 24313090
TI  - Association between language, serious adverse events, and length of stay among
      hospitalized children.
AB  - OBJECTIVE: To evaluate the risk for serious/sentinel adverse events among
      hospitalized children according to race, ethnicity, and language and to evaluate
      factors affecting length of stay associated with serious/sentinel adverse events.
      METHODS: We conducted a retrospective cohort study of all pediatric inpatients at
      a large children's hospital from October 2007 to October 2009. We evaluated the
      relationship between self-reported race, ethnicity, and primary language; with
      having a serious or sentinel adverse event, defined as an unexpected occurrence
      involving risk of death or serious injury; or a potentially harmful event
      resulting from nonstandard practice. We also examined length of stay. Clinical
      complexity was adjusted for by using Clinical Risk Groups. RESULTS: Of 33885
      patients, 8% spoke Spanish and 4% spoke other languages. Serious and sentinel
      events were rare; however, among patients with such events, 14% spoke Spanish.
      Adjusting for potential confounders, Spanish speakers trended toward an elevated
      odds of adverse event (odds ratio: 1.83 [95% confidence interval: 0.98-3.39]).
      Controlling for age, language, and clinical complexity, having an adverse event
      was associated with a nearly fivefold increase in length of stay (95% confidence
      interval: 3.87-6.12). Spanish-speaking patients with an adverse event were
      hospitalized significantly longer than comparable English speakers (26 vs 12.7
      days; P = .03 for interaction between language and adverse event). CONCLUSIONS:
      Hospitalized children from Spanish-speaking families had significantly longer
      hospital stays in association with an adverse event and may have increased odds
      of a serious or sentinel event. These findings suggest that an important
      component of patient safety may be to address communication barriers.

PMID- 24313091
TI  - Using patient characteristics to predict usefulness of abdominal computed
      tomography in children.
AB  - OBJECTIVE: The study goal was to determine whether clinical symptoms, physical
      findings, or laboratory values predict the usefulness of abdominal computed
      tomography (CT) scans in children. METHODS: We conducted a retrospective review
      of pediatric patients who received an abdominal CT scan between June 2009 and
      November 2011 at an urban medical center. A panel of pediatric hospitalists
      independently categorized each CT read as: (1) necessary for diagnosis; (2)
      unnecessary but helpful for diagnosis; or (3) neither necessary nor helpful for
      diagnosis. Two multiple logistic regression models examined 21 clinical variables
      to assess their ability to differentiate between: (1) necessary and unnecessary
      CT scans; and (2) helpful and unhelpful CT scans. RESULTS: A total of 399 CT
      scans were analyzed. Seventy (18%) of these were categorized as necessary, 103
      (26%) as unnecessary but helpful, and 226 (57%) as neither necessary nor helpful.
      Three variables were strongly correlated with necessary CT scans: leukocytosis,
      peritoneal signs, and male gender. The probability of a CT scan being necessary
      was 57% in patients with all 3 findings and 8% in those with none. Three
      variables were also strongly correlated with unnecessary but helpful CT scans:
      history of abdominal surgery, tachypnea, and leukocytosis. The probability of a
      CT scan being helpful was 84% in patients with all 3 findings and 35% in those
      with none of the 3 findings. CONCLUSIONS: The majority of abdominal CT scans were
      unnecessary and unhelpful. Knowing which clinical variables correlate strongly
      with necessary or helpful abdominal CT scans may assist clinicians in deciding
      whether to order this test; however, the predictive power of these variables
      remains relatively low.

PMID- 24313092
TI  - Outcomes and costs associated with hospitalist comanagement of medically complex
      children undergoing spinal fusion surgery.
AB  - OBJECTIVE: The goal of this study was to assess outcomes and costs associated
      with hospitalist comanagement of medically complex children undergoing spinal
      fusion surgery for neuromuscular scoliosis. METHODS: A hospitalist comanagement
      program was implemented at a children's hospital. We conducted a retrospective
      case series study of patients during 2003-2008 to compare clinical and cost
      outcomes for 87 preimplementation patients, 40 patients during a partially
      implemented program, and 80 patients during a fully implemented program. RESULTS:
      When compared with preimplementation patients, full implementation program
      patients did not demonstrate a statistically significant difference in median
      length of stay on the medical/surgical unit after transfer from the PICU (median:
      6 vs 8 days; P = .07). Patients in the full implementation group received fewer
      days of parenteral nutrition (median: 0 vs 6 days; P = .0006) and had fewer
      planned and unplanned laboratory studies on the inpatient unit. There was no
      statistically significant change in returns to the operating room (P = .08
      between preimplementation and full implementation), other complications, or 30
      day readmissions. Median hospital costs increased from preimplementation ($59372)
      to partial implementation ($89302) and remained elevated during full
      implementation ($81 651) compared with preimplementation (P = .004). Mean
      physician costs followed a similar trajectory from preimplementation ($18425) to
      partial implementation ($24101) to full implementation ($22578; P = .0006 [versus
      preimplementation]). CONCLUSIONS: A hospitalist comanagement program can
      significantly affect the care of medically complex children undergoing spinal
      fusion surgery. Initial program costs may increase.

PMID- 24313093
TI  - How best to design surgical comanagement services for pediatric surgical
      patients?

PMID- 24313094
TI  - The clinical management of preterm infants with bronchiolitis.
AB  - OBJECTIVES: The goal of this study was to determine physician management choices
      for hospitalized premature infants with bronchiolitis compared with erm infants
      and to evaluate predictors of steroid use in premature infants. METHODS: A chart
      review was conducted of premature and nonpremature infants admitted to 2
      children's hospitals with bronchiolitis. Reviewers selected charts based on
      International Classification of Diseases, Ninth Revision diagnosis codes and
      collected demographic and historical information, as well as evaluation,
      treatment, treatment effectiveness, length of stay, hospital readmission rates,
      and adverse outcomes. Reviewers compared documented rates of utilization and
      effectiveness of inhaled racemic epinephrine and albuterol between patients with
      and without a history of prematurity. Patients with a history of prematurity
      underwent subgroup analysis of factors relating to steroid use. RESULTS: A total
      of 1223 patients met the study criteria for inclusion. Premature infants
      represented 19% of all children hospitalized with bronchiolitis. These infants
      had a longer length of stay (3.8 vs 2.6 days; P < .001) and a more severe
      hospital course. Rates of inhaled therapy and steroid utilization did not differ
      between premature and term infants. There was no difference in rates of
      documented positive response to albuterol, but premature infants were more likely
      to have a positive response to epinephrine. Steroid use in premature infants was
      associated with older age, history of wheeze, and albuterol use; documentation of
      albuterol efficacy did not correlate with steroid use, however. CONCLUSIONS:
      Management decisions among term and premature infants with bronchiolitis were
      similar. Premature infants who received albuterol were more likely to receive
      steroids; however, the decision regarding steroid use was not associated with
      documentation of efficacy of albuterol.

PMID- 24313095
TI  - A quality project to improve compliance with AAP guidelines for inpatient
      management of neonatal hyperbilirubinemia.
AB  - OBJECTIVE: The goal of this study was to improve compliance with published
      guidelines regarding management of neonatal hyperbilirubinemia in infants
      admitted to a general pediatric hospital ward and to improve support for their
      breastfeeding mothers. METHODS: This quality improvement project was conducted by
      using Plan-Do-Study-Act cycles and statistical process control methods. Study
      subjects were infants > 35 weeks' gestation admitted for hyperbilirubinemia to
      the general inpatient ward of a large, freestanding pediatric hospital. We
      developed and implemented a guideline for the inpatient management of jaundiced
      neonates, with ongoing feedback given to the faculty on group performance.
      Outcome measures included monthly compliance scores based on American Academy of
      Pediatrics (AAP) guidelines for management of neonates > 35 weeks' gestation and
      the percentage of admitted jaundiced, breastfeeding infants whose mothers
      received lactation consultation during hospitalization. To determine the AAP
      compliance score, we reviewed and assigned points to each patient admission for
      completion of a standard evaluation, avoidance of unnecessary intravenous (IV)
      fluids and peripheral IV line placement, avoidance of rebound bilirubin checks
      while in the hospital, and the bilirubin level at discharge. RESULTS: Mean
      monthly AAP compliance scores increased from 60.5% of total possible points
      during the baseline period (January 2010-December 2010) to 90.4% during the
      intervention period (January 2011-December 2011). Lactation consultations
      increased from 48% during our baseline period to 63% during our early
      intervention period and to 90% during the last 5 months of our intervention.
      Length of stay was unchanged during the baseline and intervention periods.
      CONCLUSIONS: Interprofessional collaboration between nurses and physicians
      combined with a thoughtful campaign to increase awareness of published guidelines
      were successful in improving the care of infants admitted with unconjugated
      hyperbilirubinemia.

PMID- 24313096
TI  - Pediatric hospitalists collaborate to improve timeliness of discharge
      communication.
AB  - OBJECTIVES: The transition of care from hospital to primary care provider (PCP)
      at discharge carries the potential for significant information loss. There is
      evidence that the timeliness and content of discharge communication are often
      unreliable during this handoff. Suboptimal transitions of care at discharge have
      been associated with adverse outcomes, and efficient solutions are required to
      transform the current state. Our specific aim was the achievement 90%
      documentation of hospitalist-PCP communication within 2 days of hospital
      discharge in < 12 months. METHODS: As part of a grassroots collaborative
      improvement organization, pediatric hospitalist groups engaged in parallel
      quality improvement projects to improve the timeliness and reliability of
      discharge communication at their local institutions. After an initial face-to
      face meeting, e-mail and regular conference calls were used to promote shared
      effort and learning. The study period lasted 12 months, with > 16 weeks of
      continuous data required for inclusion. RESULTS: The mean rate of documentation
      of timely discharge communication across the collaborative increased from 57% to
      85% over the study period. For the 7 hospitals that were able to collect > 16
      weeks of data before July 2010, the mean rate of communication was > 90%.
      Participants reported that the context of the collaborative contributed to their
      success. CONCLUSIONS: Timely hospitalist-PCP communication was inconsistent at
      the beginning of the study. This low-resource quality improvement collaborative
      was able to achieve rapid improvement and resulted in improved perceptions of
      quality improvement knowledge among participants.

PMID- 24313097
TI  - High-fidelity simulation enhances pediatric residents' retention, knowledge,
      procedural proficiency, group resuscitation performance, and experience in
      pediatric resuscitation.
AB  - OBJECTIVE: The goal of this study was to assess the effect of high-fidelity
      simulation (HFS) pediatric resuscitation training on resident performance and
      self-reported experience compared with historical controls. METHODS: In this case
      control study, pediatric residents at a tertiary academic children's hospital
      participated in a 16-hour HFS resuscitation curriculum. Primary outcome measures
      included cognitive knowledge, procedural proficiency, retention, and self
      reported comfort and procedural experience. The intervention group was compared
      with matched-pair historical controls. RESULTS: Forty-one residents participated
      in HFS training with 32 matched controls. The HFS group displayed significant
      initial and overall improvement in knowledge (P < .01), procedural proficiency (P
      < .05), and group resuscitation performance (P < .01). Significant skill decay
      occurred in all performance measures (P < .01) with the exception of endotracheal
      intubation. Compared with controls, the HFS group reported not only greater
      comfort with most procedures but also performed more than twice the number of
      successful real-life pediatric intubations (median: 6 vs 3; P = .03).
      CONCLUSIONS: Despite significant skill decay, HFS pediatric resuscitation
      training improved pediatric resident cognitive knowledge, procedural proficiency,
      and comfort. Residents who completed the course were not only more proficient
      than historical controls but also reported increased real-life resuscitation
      experiences and related procedures.

PMID- 24313098
TI  - Perceptions of educational experience and inpatient workload among pediatric
      residents.
AB  - BACKGROUND AND OBJECTIVE: Education of residents in academic medical centers
      occurs as part of clinical care, but little is known about the relationship
      between clinical workload and educational experiences among pediatric residents.
      The goal of this study was to assess residents' perceptions of learning on
      inpatient services at a children's hospital in relation to perceived workload and
      actual patient census. METHODS: This was a prospective cohort study of pediatric
      residents at 1 urban academic children's hospital. Surveys on educational
      experience were administered weekly to residents on 12 inpatient units from
      October 2010 to June 2011. Daily peak medical inpatient census data were
      collected, and Pearson correlations were performed. RESULTS: Mean weekly response
      rate was 25%. Perceived workload was correlated with weekly peak of patient
      census for interns (r = 0.66; P= .00) and senior residents (r = 0.73; P = .00).
      Many aspects of perceived learning were negatively correlated with perceived
      workload among interns and residents in "acute care" units. Activities beyond
      direct patient care (eg, attending conferences, independent reading) revealed
      more negative correlation than educational experience during rounds. Among
      seniors, scores of aspects of perceived learning did not correlate with workload.
      CONCLUSIONS: The study found mostly negative associations between high perceived
      workload and perceived learning, especially for interns. Results suggest varied
      impact of workload on perceived learning by training year. Although patient care
      is essential for resident education, higher workload may adversely affect
      learning opportunities for pediatric trainees. More research is needed to
      identify if generalizable thresholds of patient census and/or clinical workload
      cause declines in perceived or real education.

PMID- 24313099
TI  - Association between practice setting and pediatric hospitalist career
      satisfaction.
AB  - BACKGROUND: Pediatric hospital medicine has become a viable long-term career
      choice. To retain qualified physicians, both academic and community hospital
      leaders seek to improve their job satisfaction. OBJECTIVE: The goal of this study
      was to determine whether practice in a community versus academic setting is
      associated with pediatric hospitalists' career satisfaction. METHODS: The study
      was based on data from an anonymous electronic cross-sectional survey sent to the
      American Academy of Pediatrics Section on Hospital Medicine Listserv between
      November 2009 and January 2010. Questions were rated on a standard 5-point Likert
      scale. A total career satisfaction score was calculated for each respondent by
      summing across all 23 questions. Multivariate logistic regression was conducted
      to assess job satisfaction according to practice setting. RESULTS: A total of 222
      pediatric hospitalists responded. Sixty-six percent of respondents practiced in
      an academic setting and 34% in a community hospital. Fifty-eight percent of
      academic and 42% of community hospitalists were satisfied with their careers,
      defined as a mean per-question Likert score > or = 4. Adjusting for gender,
      average daily census, percentage of complex patients, years as a hospitalist, and
      years since residency graduation, academic hospitalists were more likely than
      community hospitalists to be satisfied with their careers (adjusted odds ratio:
      2.43 [95% confidence interval: 1.25-4.72]; P = .009). CONCLUSIONS: Pediatric
      hospitalists practicing in academic settings seem more likely to be satisfied
      with their careers than those in a community hospital. Overall, however, there is
      room for improvement in career satisfaction for both groups. Further study is
      warranted to confirm and clarify these findings on a larger scale, perhaps with
      oversampling of community hospitalists.

PMID- 24313100
TI  - Commentary on association between practice setting and pediatric hospitalist
      career satisfaction; observations from two very satisfied community hospitalists.

PMID- 24313101
TI  - Intravenous acetaminophen: an alternative to opioids for pain management?

PMID- 24313102
TI  - "Mom, I'm going to be an INPATIENT doctor..." (a graduating PHM fellow's musings
      on the past, present, and future).

PMID- 24313103
TI  - Micah.

PMID- 24313104
TI  - "Compassion alone will not stop the care failings".

PMID- 24313105
TI  - Senior nurses may face prosecution.

PMID- 24313106
TI  - "Infection prevention needs the attention of staff at all levels".

PMID- 24313107
TI  - "We need to inject energy into promoting hand hygiene".

PMID- 24313108
TI  - Improving adherence to hand hygiene practice.
AB  - Hand hygiene compliance rates continue to vary between healthcare settings and
      individual professionals. This article looks at how a multimodal approach to
      infection prevention and control, using expertise from other disciplines, can
      increase compliance with hand hygiene practices.

PMID- 24313109
TI  - Promoting hand hygiene in clinical practice.
AB  - Nurses are well known and respected for championing practices that contribute to
      high standards of patient care, save lives, and help to influence other
      disciplines to do the same. Hand hygiene is one such practice. This article
      discusses the role nurses play in championing hand hygiene and explores how
      senior managers can support them in this.

PMID- 24313110
TI  - Hand hygiene--when and how should it be done?
AB  - Practising hand hygiene at the right times to prevent healthcare-associated
      infections is one of the most important patient care practices health
      professionals can undertake. However, changing behaviour to ensure staff practise
      appropriate hand hygiene requires a multifaceted approach. This article
      highlights two important aspects of the message staff need--the when and the how
      of hand hygiene.

PMID- 24313111
TI  - Influenza immunisation for healthy children.

PMID- 24313112
TI  - Identifying and treating anaemia effectively.

PMID- 24313113
TI  - Probiotics in antibiotic-associated diarrhoea.

PMID- 24313114
TI  - Using podcasts to keep patients informed.

PMID- 24313115
TI  - 60 seconds with: Jennie Fecitt.

PMID- 24313116
TI  - Cross-cultural palliative care.

PMID- 24313117
TI  - Recognise how to lead valiantly.

PMID- 24313118
TI  - Viral load monitoring: shifting paradigms in clinical practice.

PMID- 24313119
TI  - The clinical importance of hepatitis C genotyping in the United States.

PMID- 24313120
TI  - Challenges for accurate HIV diagnosis: viral genetic diversity and acute
      infection.

PMID- 24313121
TI  - HPV and Pap: shifting roles in cervical cancer screening.

PMID- 24313122
TI  - Pathology: the last digital frontier of biomedical imaging.

PMID- 24313123
TI  - ePathology: defining the new paradigm of anatomic pathology.

PMID- 24313124
TI  - A new twist on the detection of disease-causing microbes.

PMID- 24313125
TI  - Advances in point of care influenza testing technology.

PMID- 24313126
TI  - The influenza virus: disease, diagnostics, and treatment.

PMID- 24313127
TI  - Process controls: internal and external.

PMID- 24313128
TI  - Technological advances in today's hematology analyzers: how they address common
      laboratory challenges.

PMID- 24313129
TI  - Increasing lab efficiency using NMR technology.

PMID- 24313131
TI  - Julian Baines guides EKF diagnostics toward opportunities for continued growth
      and new services. Interview by Alan Lenhoff.

PMID- 24313130
TI  - Alzheimer's disease: a progress report.

PMID- 24313132
TI  - Looking forward. The American College of Surgeons: Helping surgeons cope with
      health care reform.

PMID- 24313133
TI  - Applying surgical apps: Smartphone and tablet apps prove useful in clinical
      practice.

PMID- 24313135
TI  - Choosing a physician in the Yelp era.

PMID- 24313136
TI  - Patient rankings: why patient feedback should affect our delivery of care but not
      our pay.

PMID- 24313137
TI  - Patient feedback makes us better surgeons.

PMID- 24313138
TI  - Legislated mints on the pillow.

PMID- 24313139
TI  - The ACS NSQIp quality in-training initiative: educating residents to ensure the
      future of optimal surgical care.

PMID- 24313141
TI  - Medicine still a noble calling, despite outside interference.

PMID- 24313140
TI  - IM nailing makes basketball player's recovery a snap.

PMID- 24313142
TI  - Implementation guide offers effective strategies to combat SSIs.

PMID- 24313145
TI  - From vision to action: meeting public health challenges in the Region.

PMID- 24313143
TI  - NTDB data points: what's on TV?

PMID- 24313146
TI  - Effect of delay in diagnosis on the rate of tuberculosis among close contacts of
      tuberculosis patients.
AB  - Few studies have explored diagnosis delay by tuberculosis (TB) patients and its
      effects on the rate of infection among their close contacts. A cross-sectional
      study of the close contacts of 505 newly diagnosed TB patients was conducted in a
      TB referral centre in Sana'a, Yemen from 2008 to 2010. Only the close contacts of
      89 new TB patients agreed to participate and completed the tuberculin skin test
      (TST). Of the 239 close contacts investigated, 133 (55.6%) had a positive TST
      result. Index patients were classified as long or short diagnosis delay (above or
      below the median). There was no significant difference in the number of infected
      close contacts between long and short delay index patients (Mann-Whitney U-test).
      A larger sample size, with more incentives for patients to participate and the
      use of other investigative tools could provide a better picture of the pattern of
      TB transmission among all contacts.

PMID- 24313147
TI  - Patterns of meningococcal infection in Sudan with emergence of Neisseria
      meningitidis serogroup W135.
AB  - This study was conducted during the 2004-2006 epidemic of meningitis in Sudan to
      follow-up the frequency of disease outbreak or endemic waves and to evaluate the
      new quadrivalent vaccine for actual application. Samples were collected from
      Darfur, El Gedaref, Kassala and Khartoum States and transported to the National
      Health Central Laboratory in Khartoum. Of 196 patients with clinical symptoms and
      signs of meningitis, conventional culture identified Neisseria meningitidis in 37
      (189%), confirmed by polymerase chain reaction. N. meningitidis type A was
      identified in 29 (78.4%) patients, type C in 3 (8.1%) and N. meningitidis W135 in
      5 (15.5%). The serotyping and molecular diagnosis patterns of N. meningitidis
      showed the emergence of the new strain, W135, in 5 (15.5%). The patients from the
      borders of Sudan, 3 from the West Darfur, and 1 each from El Gedaref and Kassala.
      These could be related to the movement of pilgrims through the borders to Saudi
      Arabia in the Hajj season. Serious consideration may be needed for quadrivalent
      vaccination to prevent seasonal and Hajj season outbreaks.

PMID- 24313148
TI  - First survey of cutaneous leishmaniasis in Borujerd county, western Islamic
      Republic of Iran.
AB  - Lorestan province in the Islamic Republic of Iran has not previously been known
      as a focus for cutaneous leishmaniasis (CL). Clinical and epidemiological studies
      were carried out on patients diagnosed with active CL at the central laboratory
      in Borujerd city during 1998-2010. A total of 137 patients with corroborated CL
      were studied (mean estimated annual incidence 4.36 per 100 000 inhabitants). The
      male:female ratio was > 11:1. Patients ranged in age from 8-63 years but > 70%
      were aged 21-40 years and only 1 was < or = 10 years. The rate of CL was highest
      in rural residents (56.9%) and among those working as labourers (38.0%) and
      drivers (32.8%). The rate of active lesions on the upper limbs (69.3%) was
      significantly higher than other locations, and more cases were dry sores (57.7%)
      than wet sores (42.3%). The majority of patients (61.3%) had a single active
      lesion (mean 1.8 ulcers per patient). This is the first report of CL in the area.

PMID- 24313149
TI  - Fatalities from road traffic accidents among the young in Bahrain.
AB  - In Bahrain and other Gulf countries, road traffic accidents (RTA) are recognized
      as a growing public health problem. This study described the trend of fatalities
      from RTA in Bahrain among those aged < 25 years from 2003-2010. The proportional
      mortality ratios of RTA deaths (up to 30 days from the accident) among the young
      were compared with those of all ages. The average proportion of young males
      killed by RTA in Bahrain during the 8-year period was 82.7%, with 2006 marking
      the lowest proportion among Bahraini nationals (72.2%) and the total population
      (79.2%). RTA fatalities constituted 51.3% among the Bahrainis, 20.2% of non
      Bahrainis and 39.0% of all fatalities in both sexes combined. The young in
      Bahrain were 3.5 times more likely to die from RTA than the general population.
      This paper calls on policy-makers to consolidate efforts to control this public
      health problem.

PMID- 24313150
TI  - Cigarette and waterpipe smoking associated knowledge and behaviour among medical
      students in Lebanon.
AB  - As future physicians capable of controlling tobacco dependence in the population,
      medical students are considered a main target for tobacco control interventions.
      This cross-sectional study reported on the prevalence of tobacco use (cigarettes
      and waterpipes) and associated knowledge and behaviour among 6th-year medical
      students in 2009-2010 from 6 medical schools in Lebanon. The self-administered
      questionnaire based on the Global Health Professional Survey (GHPSS) core
      questions also enquired about training in tobacco cessation approaches. All
      enrolled students were asked to participate; the response rate was 191/354
      (54.3%). The prevalence of tobacco use was 26.3% for cigarettes and 29.5% for
      waterpipes. Smoking waterpipes was the only significant predictor for cigarette
      smoking and there was no difference by sex and socioeconomic status. A minority
      reported ever receiving any formal training in treatment approaches for tobacco
      dependence. Medical schools should include tobacco dependence treatment training
      programmes in their curriculum and discourage tobacco use.

PMID- 24313151
TI  - Emotional abuse among children: a study in Jeddah, Saudi Arabia.
AB  - Emotional abuse is the most hidden and underestimated form of child maltreatment.
      We report an exploratory study in Saudi Arabia of the rate and types of emotional
      abuse among children and its association with selected variables. A convenience
      sample of 60 children aged 12-18 years was recruited from 3 malls in Jeddah. A
      specially designed, self-administered questionnaire was completed in confidence
      by the children with the consent of parents. Overall 90% of participants reported
      at least 1 form of rejecting emotional abuse and 61.7% at least 1 form of
      ignoring or terrorizing types of abuse. Chronic illness among parents was
      significantly positively correlated with terrorizing emotional abuse. There was a
      statistically significant negative correlation between mothers' relationship with
      the child and ignoring and terrorizing types of emotional abuse. Further research
      is needed about the community prevalence, correlates and consequences of child
      emotional abuse in Saudi Arabia.

PMID- 24313152
TI  - Experiences of intimate-partner violence and contraception use among ever-married
      women in Jordan.
AB  - This study explored the relationship between intimate partner violence (IPV) and
      current contraception use among ever-married women in Jordan. Analysing a sample
      (n = 3434) from the 2007 Jordan demographic and health survey, women who reported
      ever experiencing severe physical violence from their husband were significantly
      less likely to use contraception than women who did not report severe physical
      violence (OR = 0.34). Conversely, women who reported ever experiencing sexual IPV
      were significantly more likely to use contraception (OR = 1.50). Emotional and
      less severe physical IPV were not significantly related to contraception use.
      Education, wealth, age, number of children, and fertility preferences were
      positively associated with contraception use, while residence in the Badia area
      and consanguineous marriages were negatively associated with contraception use.
      The findings have implications for the provision of IPV screening and
      contraception services in Jordan, as well as the specification of services for
      women most vulnerable to IPV.

PMID- 24313153
TI  - Ventilator-associated pneumonia in a teaching hospital in Tehran and use of the
      Iranian Nosocomial Infections Surveillance Software.
AB  - Ventilator-associated pneumonia is the most common health-care-associated
      infection in the intensive care unit (ICU) and computer-assisted diagnosis and
      surveillance is called for. The frequency of ventilator-associated pneumonia was
      assessed prospectively during a 6-month period in the ICUs of a teaching hospital
      in Tehran, Islamic Republic of Iran. To determine the accuracy of the Iranian
      Nosocomial Infections Surveillance (INIS) system, patient data were input to the
      software and compared with physicians' judgement. The frequency of ventilator
      associated pneumonia was 21.6%, or 9.96 episodes per 1000 ventilator days. The
      duration of admission to the ICU, duration of mechanical ventilator and number of
      re-intubations were significantly higher in patients who developed pneumonia. The
      INIS system identified 100% of cases, with no false-positive or false-negative
      results. Compared with developed countries, the frequency of ventilator
      associated pneumonia was high in our ICUs, and INIS software was accurate in
      diagnosing nosocomial infection.

PMID- 24313154
TI  - Communicable diseases in the Eastern Mediterranean Region: prevention and control
      2010-2011.
AB  - One-third of all morbidities and mortalities in the Eastern Mediterranean Region
      are attributed to communicable diseases. A continued situation of war and
      conflict, and growing political unrest in the Region, coupled with factors such
      as travel and migration, and insufficient infrastructure and inadequate technical
      and managerial capacity ofthe programmes are the major challenges. Despite these
      challenges, the Region continued making progress towards the elimination of
      specific diseases such as lymphatic filariasis, measles, malaria, schistosomiasis
      and dracunculiasis during 2010-11. Coverage for vaccine-preventable diseases was
      enhanced. Preparedness and response to emerging (e.g. dengue fever in Pakistan
      and Yemen) and re-emerging (e.g. cholera in Sudan) infections was improved. The
      Region has continued its efforts for controlling tuberculosis and curbing
      HIV/AIDS. Looking ahead, the Region aims to improve surveillance and response
      capacities, legislation issues, coordination, bio-risk and bio-security and
      quality management in the coming years.

PMID- 24313155
TI  - Strategic approach to control of viral haemorrhagic fever outbreaks in the
      Eastern Mediterranean Region: report from a regional consultation.
AB  - The viral haemorrhagic fevers (VHF) are a growing public health threat in the
      Eastern Mediterranean Region. Nearly all of them are of zoonotic origin. VHF
      often cause outbreaks with high fatalities and, except for yellow fever,
      currently there are no specific treatment or vaccination options available. In
      response to this growing threat, the Regional Office for the Eastern
      Mediterranean of the World Health Organization convened a technical consultation
      in Tehran on 27-30 November 2011 to review the current gaps in prevention and
      control of VHF outbreaks in the Region. The meeting recommended a number of
      strategic public health approaches for prevention and control of VHF outbreaks
      through synergizing effective collaboration between the human and animal health
      sectors on areas that involve better preparedness, early detection and rapid
      response. Implementation of these approaches would require working together with
      vision, commitment and a sense of purpose involving partnerships and cooperation
      from all relevant sectors.

PMID- 24313156
TI  - A case of vocal tic: an unusual presentation of neurobrucellosis.

PMID- 24313157
TI  - Author's reply: To PMID 23882967.

PMID- 24313158
TI  - Prehypertension among young adult females in Dammam, Saudi Arabia.

PMID- 24313159
TI  - Epigenetics--new frontier for alcohol research.

PMID- 24313161
TI  - Dysregulation of microRNA expression and function contributes to the etiology of
      fetal alcohol spectrum disorders.
AB  - MicroRNAs (miRNAs) are members of a large class of non-protein-coding RNA (ncRNA)
      molecules that represent a significant, but until recently unappreciated, layer
      of cellular regulation. Assessment of the generation and function of miRNAs
      suggests that these ncRNAs are vulnerable to interference from genetic,
      epigenetic, and environmental factors. A small but rapidly expanding body of
      studies using a variety of animal- and cell culture-based experimental models
      also has shown that miRNAs are important targets of alcohol during fetal
      development and that their dysregulation likely plays a significant role in the
      etiology of fetal alcohol spectrum disorders (FASD). Accordingly, an analysis of
      the regulation and function of these miRNAs may yield important clues to the
      management of FASD.

PMID- 24313160
TI  - Alcohol metabolism and epigenetics changes.
AB  - Metabolites, including those generated during ethanol metabolism, can impact
      disease states by binding to transcription factors and/or modifying chromatin
      structure, thereby altering gene expression patterns. For example, the activities
      of enzymes involved in epigenetic modifications such as DNA and histone
      methylation and histone acetylation, are influenced by the levels of metabolites
      such as nicotinamide adenine dinucleotide (NAD), adenosine triphosphate (ATP),
      and S-adenosylmethionine (SAM). Chronic alcohol consumption leads to significant
      reductions in SAM levels, thereby contributing to DNA hypomethylation. Similarly,
      ethanol metabolism alters the ratio of NAD+ to reduced NAD (NADH) and promotes
      the formation of reactive oxygen species and acetate, all of which impact
      epigenetic regulatory mechanisms. In addition to altered carbohydrate metabolism,
      induction of cell death, and changes in mitochondrial permeability transition,
      these metabolism-related changes can lead to modulation of epigenetic regulation
      of gene expression. Understanding the nature of these epigenetic changes will
      help researchers design novel medications to treat or at least ameliorate alcohol
      induced organ damage.

PMID- 24313162
TI  - Alcohol, DNA methylation, and cancer.
AB  - Cancer is one of the most significant diseases associated with chronic alcohol
      consumption, and chronic drinking is a strong risk factor for cancer,
      particularly of the upper aerodigestive tract, liver, colorectum, and breast.
      Several factors contribute to alcohol-induced cancer development (i.e.,
      carcinogenesis), including the actions of acetaldehyde, the first and primary
      metabolite of ethanol, and oxidative stress. However, increasing evidence
      suggests that aberrant patterns of DNA methylation, an important epigenetic
      mechanism of transcriptional control, also could be part of the pathogenetic
      mechanisms that lead to alcohol-induced cancer development. The effects of
      alcohol on global and local DNA methylation patterns likely are mediated by its
      ability to interfere with the availability of the principal biological methyl
      donor, S-adenosylmethionine (SAMe), as well as pathways related to it. Several
      mechanisms may mediate the effects of alcohol on DNA methylation, including
      reduced folate levels and inhibition of key enzymes in one-carbon metabolism that
      ultimately lead to lower SAMe levels, as well as inhibition of activity and
      expression of enzymes involved in DNA methylation (i.e., DNA methyltransferases).
      Finally, variations (i.e., polymorphisms) of several genes involved in one-carbon
      metabolism also modulate the risk of alcohol-associated carcinogenesis.

PMID- 24313163
TI  - In utero alcohol exposure, epigenetic changes, and their consequences.
AB  - Exposure to alcohol has serious consequences for the developing fetus, leading to
      a range of conditions collectively known as fetal alcohol spectrum disorders
      (FASD). Most importantly, alcohol exposure affects the development of the brain
      during critical periods of differentiation and growth, leading to cognitive and
      behavioral deficits. The molecular mechanisms and processes underlying the
      teratogenic effects of alcohol exposure remain poorly understood and are complex,
      because the specific effects depend on the timing, amount, and duration of
      exposure as well as genetic susceptibility. Accumulating evidence from studies on
      DNA methylation and histone modification that affect chromatin structure, as well
      as on the role of microRNAs in regulating mRNA levels supports the contribution
      of epigenetic mechanisms to the development of FASD. These epigenetic effects are
      difficult to study, however, because they often are cell-type specific and
      transient in nature. Rodent models play an important role in FASD research.
      Although recent studies using these models have yielded some insight into
      epigenetic mechanisms affecting brain development, they have generated more
      questions than they have provided definitive answers. Researchers are just
      beginning to explore the intertwined roles of different epigenetic mechanisms in
      neurogenesis and how this process is affected by exposure to alcohol, causing
      FASD.

PMID- 24313164
TI  - Epigenetic effects of ethanol on the liver and gastrointestinal system.
AB  - The widening web of epigenetic regulatory mechanisms also encompasses ethanol
      induced changes in the gastrointestinal (GI)-hepatic system. In the past few
      years, increasing evidence has firmly established that alcohol modifies several
      epigenetic parameters in the GI tract and liver. The major pathways affected
      include DNA methylation, different site-specific modifications in histone
      proteins, and microRNAs. Ethanol metabolism, cell-signaling cascades, and
      oxidative stress have been implicated in these responses. Furthermore, ethanol
      induced fatty liver (i.e., steatohepatitis) and progression of liver cancer
      (i.e., hepatic carcinoma) may be consequences of the altered epigenetics.
      Modification of gene and/or protein expression via epigenetic changes also may
      contribute to the cross-talk among the GI tract and the liver as well as to
      systemic changes involving other organs. Thus, epigenetic effects of ethanol may
      have a central role in the various pathophysiological responses induced by
      ethanol in multiple organs and mediated via the liver-GI axis.

PMID- 24313165
TI  - Epigenetic events in liver cancer resulting from alcoholic liver disease.
AB  - Epigenetic mechanisms play an extensive role in the development of liver cancer
      (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease
      (ALD) as well as in liver disease associated with other conditions. For example,
      epigenetic mechanisms, such as changes in the methylation and/or acetylation
      pattern of certain DNA regions or of the histone proteins around which the DNA is
      wrapped, contribute to the reversion of normal liver cells into progenitor and
      stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e.,
      ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism
      results in the formation of compounds that can cause changes in DNA methylation
      and interfere with other components of the normal processes regulating DNA
      methylation. Alcohol exposure also can alter histone acetylation/deacetylation
      and methylation patterns through a variety of mechanisms and signaling pathways.
      Alcohol also acts indirectly on another molecule called toll-like receptor 4
      (TLR4) that is a key component in a crucial regulatory pathway in the cells and
      whose dysregulation is involved in the development of HCC. Finally, alcohol use
      regulates an epigenetic mechanism involving small molecules called miRNAs that
      control transcriptional events and the expression of genes important to ALD.

PMID- 24313166
TI  - Epigenetic control of gene expression in the alcoholic brain.
AB  - Chronic alcohol exposure causes widespread changes in brain gene expression in
      humans and animal models. Many of these contribute to cellular adaptations that
      ultimately lead to behavioral tolerance and alcohol dependence. There is an
      emerging appreciation for the role of epigenetic processes in alcohol-induced
      changes in brain gene expression and behavior. For example, chronic alcohol
      exposure produces changes in DNA and histone methylation, histone acetylation,
      and microRNA expression that affect expression of multiple genes in various types
      of brain cells (i.e., neurons and glia) and contribute to brain pathology and
      brain plasticity associated with alcohol abuse and dependence. Drugs targeting
      the epigenetic "master regulators" are emerging as potential therapeutics for
      neurodegenerative disorders and drug addiction.

PMID- 24313167
TI  - Prenatal alcohol exposure and cellular differentiation: a role for Polycomb and
      Trithorax group proteins in FAS phenotypes?
AB  - Exposure to alcohol significantly alters the developmental trajectory of
      progenitor cells and fundamentally compromises tissue formation (i.e.,
      histogenesis). Emerging research suggests that ethanol can impair mammalian
      development by interfering with the execution of molecular programs governing
      differentiation. For example, ethanol exposure disrupts cellular migration,
      changes cell-cell interactions, and alters growth factor signaling pathways.
      Additionally, ethanol can alter epigenetic mechanisms controlling gene
      expression. Normally, lineage-specific regulatory factors (i.e., transcription
      factors) establish the transcriptional networks of each new cell type; the cell's
      identity then is maintained through epigenetic alterations in the way in which
      the DNA encoding each gene becomes packaged within the chromatin. Ethanol
      exposure can induce epigenetic changes that do not induce genetic mutations but
      nonetheless alter the course of fetal development and result in a large array of
      patterning defects. Two crucial enzyme complexes--the Polycomb and Trithorax
      proteins--are central to the epigenetic programs controlling the intricate
      balance between self-renewal and the execution of cellular differentiation, with
      diametrically opposed functions. Prenatal ethanol exposure may disrupt the
      functions of these two enzyme complexes, altering a crucial aspect of mammalian
      differentiation. Characterizing the involvement of Polycomb and Trithorax group
      complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly
      enhance understanding of the role that epigenetic programming plays in this
      complex disorder.

PMID- 24313170
TI  - Fatal pulmonary thromboembolism after prolonged physical immobilization in
      hospitalized psychiatric patients.
AB  - BACKGROUND/AIM: Pulmonary thromboembolism (PTE) may be one of the causes of
      sudden death in hospitalized psychiatric patients. The aim of our study was to
      investigate whether fatal PTE in these patients may be the result of their
      prolonged physical immobilization, particularly when there were associated risk
      factors, and to emphasize the importance of this problem. METHODS: A
      retrospective analysis of medical records of psychiatric patients died suddenly
      at the Department of Intensive Care of the Clinic of Psychiatry "Dr Laza
      Lazarevic", Belgrade, in the period January 1, 2010 - December 31, 2011, was
      performed. Data of those for which the autopsy showed PTE as the immediate cause
      of death were extracted, and the presence of risk factors for the development of
      deep vein thrombosis analyzed. RESULTS: In the observed period, out of 4,001
      hospitalized psychiatric patients 53 died, and for 18 of them autopsy was
      required due to sudden death. In five patients, autopsy revealed PTE as a direct
      and sole cause of death. All the five patients were males, mean age 45.2 years,
      and during hospitalization all received strong antipsychotics and diazepam. Of
      the total duration of their hospital stay (mean 8.2 days), they were temporarily
      immobilized during an average 4.2 days. Four of them had acute infection, three
      were active smokers, and the two had a body mass index > 30 kg/m2. CONCLUSION:
      Our results suggest a possible link between prolonged physical immobilization of
      psychiatric patients who also receive antipsychotic therapy, and total PTE.

PMID- 24313168
TI  - Circadian disruption: potential implications in inflammatory and metabolic
      diseases associated with alcohol.
AB  - Circadian rhythms are a prominent and critical feature of cells, tissues, organs,
      and behavior that help an organism function most efficiently and anticipate
      things such as food availability. Therefore, it is not surprising that disrupted
      circadian rhythmicity, a prominent feature of modern-day society, promotes the
      development and/or progression of a wide variety of diseases, including
      inflammatory, metabolic, and alcohol-associated disorders. This article will
      discuss the influence of interplay between alcohol consumption and circadian
      rhythmicity and how circadian rhythm disruption affects immune function and
      metabolism as well as potential epigenetic mechanisms that may be contributing to
      this phenomenon.

PMID- 24313171
TI  - Impaired endothelial function in lone atrial fibrillation.
AB  - BACKGROUND/AIM: Impaired endothelial function has been previously documented in
      patients with atrial fibrillation (AF) and underlying comorbidities or older
      patients with idiopathic AF. The aim of this study was to evaluate systemic
      endothelial function in younger AF patients (less than < 60 years old) with lone
      AF (that is, without associated cardiopulmonary comorbidities, including arterial
      hypertension), by comparing brachial artery flow-mediated dilation (FMD) in lone
      AF patients with FMD of healthy subjects in sinus rhythm. METHODS: Two groups of
      participants were prospectively enrolled. The first group comprised of 38 AF
      patients (the mean age 45 +/- 11 years, 68% male) with persistent (> 7 days) lone
      AF. The second group comprised of 28 healthy controls in sinus rhythm (the mean
      age 43 +/- 13, 53% male), matched by age, gender and atherosclerotic risk
      factors. All the participants underwent physical examination, laboratory analysis
      [including determination of C-reactive protein (CRP)], standard echocardiography
      and exercise-stress testing. Brachial artery FMD and endothelium independent
      dilation (NMD) were assessed with a high-resolution ultrasound probe and arterial
      diameters taken from 5 consecutive cardiac cycles were averaged for each
      measurement to accommodate to beat-to-beat flow variations in AF. RESULTS: There
      were no differences between the 2 groups regarding age, gender and most clinical,
      laboratory and echocardiographic characteristics (all p > 0.05), apart from the
      increased heart rate (p = 0.018), body mass index (p = 0.027), CRP levels (p =
      0.007) and left atrial anteroposterior dimension (p < 0.001) in AF patients. FMD
      of AF patients [median value 5.0%, interquartile range (IQR) 2.87%-7.50%] was
      significantly lower (p < 0.001) than FMD of healthy controls (median value 8.85%,
      IQR 5.80%-12.50%), whereas there were no differences in median NMD values (p >
      0.05). In the multivariate analysis, the independent FMD determinants in our
      study population were the presence of AF, smoking and total cholesterol levels
      (all p < 0.001). In patients with AF, the strongest independent FMD determinant
      was arrhythmia duration (p < 0.001), followed by smoking (p = 0.013) and total
      cholesterol levels (p = 0.045). CONCLUSIONS: Our findings confirm that sustained
      AF is associated with systemic endothelial dysfunction even in relatively young
      patients with no cardiovascular disorders or risk factors. AF is an independent
      contributor to lower FMD and a prolonged arrhythmia duration may confer the risk
      for more profound endothelial damage.

PMID- 24313172
TI  - Long-term outcome of a modified balloon dilatation in the treatment of patients
      with achalasia.
AB  - BACKGROUND/AIM: Balloon dilatation is a standard approach to the initial
      achalasia treatment. Modified dilatation is also applied to rise efficacy and to
      lower complications. METHODS: A total of 57 patients were analysed within a
      median follow-up of 8.2 years. No premedication was used, dilatation was
      performed up to the pain treshold, while introduction and positioning of a
      dilatator was done in combination of endoscopic and radiological control.
      Dilatation effect was estimated by both Kim Symptom Scoring and objective
      parameters: body weight rise and radiological scintigraphic findings. RESULTS:
      Excellent and good results were obtained in 50 (88%) of the patients, while in 7
      (12%) of the patients surgery was performed. There was no difference in
      dilatation efficacy regarding sex of the patients, but the results were better in
      the patients above 40 years. Duration of symptoms, body weight loss, esophageal
      lumen width do not indicate the definitive dilatation outcome. Esophageal
      scintigraphy and body weight increase were in a direct correlation with the
      effect of dilatation measured with the Kim Symptom Scoring. After the one to two
      repeated dilatations the efficacy increased from 74% to 88% justifying the
      repetition of dilatation. In 2 (3.57%) of the patients, that is in 2.65% of the
      totally dilated patients, perforation was recorded. There was no lethal outcome
      of dilatation, and the other complications were not clinically significant.
      CONCLUSION: Modified balloon dilatation can be recommended for initial method in
      achalasia treatment due to high efficacy, easy performance in daily hospital
      while complications are in standard range.

PMID- 24313173
TI  - Size of the lower third molar space in relation to age in Serbian population.
AB  - BACKGROUND/AIM: It is considered that the shortage of space is the major cause of
      the third molar impaction. The aim of this study was to establish the frequency
      of insufficient lower third molar eruption space in Serbian population, to
      question the differences in this frequency in the subjects of different age, to
      determine the influence of the lower third molar space (retromolar space) size on
      third molar eruption, and to investigate a possible correlation between the size
      of gonial angle and the space/third molar width ratio. METHODS: Digital
      orthopantomograms were taken from 93 patients divided into two groups: early
      adult (16-18 years of age) and adult (18-26) patients. Retromolar space,
      mesiodistal third molar crown width, gonial angle and eruption levels were
      measured. RESULTS: The space/third molar width in early adult subjects was
      smaller (p < 0.0001) and insufficient space was significantly more frequent (p =
      0.0003) than in adult patients. Considerably more third molars erupted in case of
      enough space in both age groups (p < 0.0001). There was no difference between the
      means of gonial angle size in relations to the available space. CONCLUSIONS: The
      retromolar space/third molar width ratio is more favorable in adult subjects.
      Gonial angle is not in correlation with the retromolar space/third molar width
      ratio.

PMID- 24313169
TI  - Epigenetic targets for reversing immune defects caused by alcohol exposure.
AB  - Alcohol consumption alters factors that modify gene expression without changing
      the DNA code (i.e., epigenetic modulators) in many organ systems, including the
      immune system. Alcohol enhances the risk for developing several serious medical
      conditions related to immune system dysfunction, including acute respiratory
      distress syndrome (ARDS), liver cancer, and alcoholic liver disease (ALD). Binge
      and chronic drinking also render patients more susceptible to many infectious
      pathogens and advance the progression of HIV infection by weakening both innate
      and adaptive immunity. Epigenetic mechanisms play a pivotal role in these
      processes. For example, alcohol-induced epigenetic variations alter the
      developmental pathways of several types of immune cells (e.g., granulocytes,
      macrophages, and T-lymphocytes) and through these and other mechanisms promote
      exaggerated inflammatory responses. In addition, epigenetic mechanisms may
      underlie alcohol's ability to interfere with the barrier functions of the gut and
      respiratory systems, which also contribute to the heightened risk of infections.
      Better understanding of alcohol's effects on these epigenetic processes may help
      researchers identify new targets for the development of novel medications to
      prevent or ameliorate alcohol's detrimental effects on the immune system.

PMID- 24313174
TI  - Reliability of conventional shade guides in teeth color determination.
AB  - BACKGROUND/AIM: Color matching in prosthodontic therapy is a very important task
      because it influences the esthetic value of dental restorations. Visual shade
      matching represents the most frequently applied method in clinical practice.
      Instrumental measurements provide objective and quantified data in color
      assessment of natural teeth and restorations. In instrumental shade analysis, the
      goal is to achieve the smallest deltaE value possible, indicating the most
      accurate shade match. The aim of this study was to evaluate the reliability of
      commercially available ceramic shade guides. METHODS: VITA Easyshade
      spectrophotometer (VITA, Germany) was used for instrumental color determination.
      Utilizing this device, color samples of ten VITA Classical and ten VITA 3D -
      Master shade guides were analyzed. Each color sample from all shade guides was
      measured three times and the basic parameters of color quality were examined:
      deltaL, deltaC, deltaH, deltaE, deltaElc. Based on these parameters
      spectrophotometer marks the shade matching as good, fair or adjust. RESULTS:
      After performing 1,248 measurements of ceramic color samples, frequency of
      evaluations adjust, fair and good were statistically significantly different
      between VITA Classical and VITA 3D Master shade guides (p = 0.002). There were
      27.1% cases scored as adjust, 66.3% as fair and 6.7% as good. In VITA 3D - Master
      shade guides 30.9% cases were evaluated as adjust, 66.4% as fair and 2.7% cases
      as good. CONCLUSION: Color samples from different shade guides, produced by the
      same manufacturer, show variability in basic color parameters, which once again
      proves the lack of precision and nonuniformity of the conventional method.

PMID- 24313175
TI  - Prevalence and quality of life in high school pupils with acne in Serbia.
AB  - BACKGROUND/AIM: Acne is a common problem in adolescent children with considerable
      emotional and psychological effects. The aim of this study was to determine the
      self-reported prevalence of acne and to assess its impact on the quality of life
      in high school pupils in Serbia. METHODS: The cross-sectional study was conducted
      in May 2011 in two medical high schools in Serbia. Only pupils who gave a written
      informed consent to participate in the study (n = 440) were asked to fill in two
      questionnaires: short demographic questionnaire and Cardiff Acne Disability Index
      (CADI), a disease-specific questionnaire measuring disability induced by acne.
      Internal consistency (tested by Cronbach's alpha) and item-total score
      correlations (Spearman's correlation analysis) were used for reliability
      analyses. RESULTS: The study population consisted of 440 pupils, 281 from
      Belgrade and 159 from Uzice. Among them 371 (84.3%) were girls and 69 (15.7%)
      boys, with similar sex distribution in Belgrade and Uzice. The total mean age of
      pupils was 16.48 years (SD = 0.55). Out of 440 pupils 228 (51.8%) self-reported
      their acne. The acne prevalence was significantly higher in pupils from Uzice
      (73.6%) than in those from Belgrade (39.6%). The overall mean CADI score for the
      whole sample was 2.87 +/- 2.74, with the similar quality of life impairment in
      adolescents from Belgrade and from Uzice. The mean Cronbach's alpha was 0.82.
      CONCLUSION: This study shows that the quality of life impairment due to acne is
      mild for the majority of the affected pupils. The Serbian version of the CADI is
      a reliable, valid, and valuable tool for assessing the impact of acne on the
      quality of life.

PMID- 24313176
TI  - Psychosocial characteristics and motivational factors in woman seeking cosmetic
      breast augmentation surgery.
AB  - BACKGROUND/AIM: There are various opinions regarding the factors motivating women
      to undergo breast augmentation. The aim of this study was to estimate motivation
      for augmentation mammaplasty (AM), self-esteem and body image perception in
      breast augmentation patients. METHODS: This prospective study involved AM
      patients operated in the Clinical Center of Vojvodina during a 3-year period. A
      total of 45 patients responded to our package of questionnaires designed to
      assess motivation for surgery, self-esteem level and body image perception. Those
      patients were compared to the control group of women who did not want to change
      their breast size, and who were similar in their age, social status and education
      level. Our package of questionnaires included a general questionnaire,
      Photographic Figure Rating Scale (PFRS) and Rosenberg's Self-Esteem Scale.
      RESULTS: Differences in marital status, educational level, habitation and
      employment status were statistically insignificant, but there was a significantly
      lower body mass index (BMI) in the operated women. Considering motives for
      surgery, a few factors were distinguished: desire to feel more feminine (82.2%),
      confident (75.5%) and attractive (73.3%), to feel less shy with men (64.4%), to
      improve their sex life (46.5%), teasing history (42.2%) and easier to find a
      partner (11.1%) and job (2.2%). Both groups demonstrated a high self-esteem
      level, but in the the AM group results were lower than in the control group. The
      mean current self-rating by the PFRS in the group AM was lower than in the
      control group (4.28 +/- 1.3 vs 5.12 +/- 1.23, respectively) and this coincided
      with lower BMI in the AM group. The women in the AM group had chosen
      significantly smaller body size as maximally attractive, and had chosen a
      narrower attractive body size range than the women in the control group.
      CONCLUSION. Preoperative evaluation of patients' motives for surgery can help
      surgeons to exclude woman with unrealistic expectations and different
      psychological problems.

PMID- 24313177
TI  - Correlation between extraintestinal manifestations and clinical parameters with
      the histologic activity index in patients with inflammatory bowel diseases.
AB  - BACKGROUND/AIM: Crohn's disease (CD) and ulcerative colitis (UC) are chronic,
      idiopathic, inflammatory diseases of the digestive tract. The aim of this study
      was to determine a possible correlation between the clinical parameters of the
      disease activity degree and the presence of extraintestinal manifestations with
      disease activity histopathological degree, in patients presented with CD and UC.
      METHODS: This cross-sectional study included 134 patients (67 with CD and UC,
      respectively) treated at the Clinic of Gastroenterology, Clinical Center of
      Serbia, Belgrade. After clinical, laboratory, endoscopic, histopathologic and
      radiologic diagnostics, the patients were divided into two groups according to
      their histopathological activity. The group I comprised 79 patients whose values
      of five-grade histopathological activity were less than 5 (45 with CD and 34 with
      UC), while the group II consisted of 55 patients with the values higher than 5
      (22 with CD and 33 with UC). The CD activity index (CDAI) and Truelove and Witts'
      scale of UC were used for clinical evaluation of the disease activity. RESULTS:
      CD extraintestinal manifestations were present in 28.9% and 63.6% of the patients
      in the groups I and II, respectively (p < 0.05). Comparison of the mean CDAI
      values found a significant difference between these two patients groups (the
      group I: 190.0 +/- 83.0, the group II: 263.4 +/- 97.6; p < 0.05). No correlation
      of extraintestinal manifestations of the disease, Truelove and Witts' scale and
      histological activity was found in UC patients (p > 0.05). CONCLUSION: In the
      patients presented with CD, the extraintestinal manifestations with higher CDAI
      suggested a higher degree of histopathological activity. On the contrary, in the
      UC patients, Truelove and Witts' scale and extraintestinal manifestations were
      not valid predictors of the disease histopathological activity.

PMID- 24313178
TI  - Combined spinal-epidural technique: single-space vs double distant space
      technique.
AB  - BACKGROUND/AIM: Several combined spinal-epidural (CSE) anesthesia techniques have
      been described. This study was designed to compare the single space ("needle
      through-needle") technique (SST) and the double distant space technique (DDS)
      with regards to the time needed for the procedure, patient discomfort during the
      procedure and patient's preference technique. METHODS: This prospective,
      randomized single-blind study included 156 patients undergoing colorectal surgery
      under general anesthesia and CSE. All neuraxial blocks were performed before
      general anesthesia induction. DDS group of patients had thoracic epidural
      catheter placed at T6-7 or T7-8, followed by subarachnoid injection at the L2-3
      interspace. The SST group of patients had a single injection using the needle
      through-needle technique (Espocan needle) at L2-3. The epidural catheter was used
      for postoperative analgesia for 72 hours. Body habitus, spinal anatomy and spinal
      landmarks were assessed preoperatively. The number of epidural and spinal
      punctures, the feeling that the dura is perforated (dural perforation click) and
      the time needed to perform CSE were also recorded. Complications during epidural
      catheter placement and perioperative and postoperative epidural catheter function
      and patient preference for the anesthetic procedure were recorded. RESULTS:
      Epidural and subarachnoid spaces were successfully identified in all the
      patients. Duration of CSE procedure, the number of spinal punctures, dural click
      feeling and the effects of test dose did not differ between the groups. The
      patients in both groups (90% of DDS and 87% of SST) would choose CSE as preferred
      method in the future. The CSE procedure was painful for 16% of DDS vs 20% of SST
      patients. A significant correlation between time needed for CSE technique
      performance and body habitus (r = 0.338, p < 0.01), spinal landmarks (r = 0.452,
      p < 0.001) and anatomy (r = 0.265, p < 0.05) was found in the SST group. There
      was no correlation between the number of epidural/spinal punctures and epidural
      bacteriological findings. There was no correlation between the patients' choice
      of the CSE technique and the number of spinal punctures, duration of CSE
      procedure and epidural catheter stay. CONCLUSION: The two CSE techniques did not
      differ with regards to the procedure time and patient's preference. Procedure
      time correlated with body habitus, spinal landmarks and the anatomy in the SST
      group.

PMID- 24313179
TI  - Risk factors and preventive measures for occupational diseases in dental
      technicians.

PMID- 24313180
TI  - Adhesive capsulitis: how to treat your patient?

PMID- 24313181
TI  - Brain metastases of choriocarcinoma--a report on two cases.
AB  - INTRODUCTION: Gestational trophoblastic diseases (GTD) are a spectrum of tumors
      with a various of biological behavior and potential for metastases. It consists
      of hydatiform mole, invasive mole, choriocarcinoma and placental site
      trophoblastic tumor. Choriocarcinoma presents a very aggressive tumor with high
      malignant potential. CASE REPORT: We presented the two cases of choriocarcinoma
      with brain metastases. The first one was manifested by neurological deterioration
      as the first sign of metastasis, while the second patient had firstly
      metrorrhagia and in the further couse neurological disturbances that suggested
      the presence of brain tumor. In both cases we applied a combined treatment of
      surgery, chemotherapy and radiation therapy. Both patient survived with high
      quality of life. CONCLUSION: A successful outcome of brain metastases of
      choriocarcinoma was obtained by the use of a combined treatment of surgery,
      chemotherapy and radiation therapy. In cases of young women with brain
      metastases, gynecological malignancy should be always considered.

PMID- 24313182
TI  - Extramedullary plasmacytoma of the tongue base: a rare presentation of head and
      neck plasmacytoma.
AB  - INTRODUCTION: Special entities like solitary bone plasmocytoma (SBP) or
      extramedullary plasmacytoma (EMP) can be found in a less than 5% of patients with
      plasma cell disorders. EMP of the tongue represents very rare localization of the
      head and neck plasmacytoma. CASE REPORT: We report a case of 78-years-old woman
      who developed EMP of the tongue base detected by the magnetic resonance imaging
      (MRI) of the head and neck region. Immunohistochemical profile of the tumor
      tissue biopsy (CD38, IgG, kappa positivity) indicated diagnosis of EMP. The
      diagnosis was established with additional staging which confirmed the absence of
      other manifestation of the disease. The patient was treated with 40 Gy of
      radiotherapy in 20 doses resulting in the achievement of the complete remission
      of the disease. This case was discussed with the reference to the literature.
      CONCLUSION: EMP of the tongue base is a very rare entity of plasma cell
      dyscrasias. Appropriate irradiation results in the achievement of a long-term
      remission and a potential cure of the disease.

PMID- 24313183
TI  - Listeria monocytogenes meningitis in an immunocompetent 18-year-old patient as a
      possible diagnostic and therapeutical problem.
AB  - INTRODUCTION: Listeria monoytogenes is the third most frequent cause of bacterial
      meningitis in adults. It commonly affects persons with defective cell-mediated
      immunity or advanced age, and only a few patiens with no underlying
      predisposition have been reported. CASE REPORT: We presented an previously
      healthy, 18-year-old man with typical clinical features of meningitis. On the
      account of earlier treatment with ceftriaxone and cerebrospinal fluid finding, an
      assumption of partially treated bacterial meningitis was made. The initial
      treatment with vancomycin and ceftriaxone, substituted on day 4 with meropenem,
      did not produce any clinical effect. On day 6 Listeria monocytogenes was isolated
      and, even as late as that, the administration of ampicillin was followed by
      complete recovery of the patient. CONCLUSION: In younger, immunocompetent
      individuals, in spite of the existent diagnostic and therapeutic problems, the
      subacute course of Listeria monocytogenes meningitis provides enough time for
      appropriate treatment and favorable disease outcome.

PMID- 24313184
TI  - [Prognostic value of the expression of adhesion molecules for non-clear-cell
      variants of renal cell carcinoma].
AB  - The prognostic value of the expression of the adhesion molecules CD44, EMA, and E
      cadherin was studied using surgical specimens of 105 renal cell carcinomas (54
      papillary, 39 chromophobic, and 12 clear-cell ones). Stages 3-4 tumors showed
      hyperexpression of all the above proteins (the distribution was estimated by chi2
      and Fisher's exact tests). Furthermore, CD44 was found to be an independent
      unfavorable factor to predict renal cell carcinoma: with its hyperexpression, the
      5-year estimated survival rate decreased by 52% (Kaplan-Meier method; p = 0.018).
      The expression of EMA and E-cadherin was significantly associated with the stage
      and, to some extent, grade of tumor differentiation; however, it is necessary to
      study more observations to define the prognostic role of these proteins.

PMID- 24313185
TI  - [Morphological and immunohistochemical features of the thymus structure in
      neonatal infants with congenital heart diseases].
AB  - The paper gives the results of morphological and immunohistochemical studies of
      the thymus in congenital hypoxia induced by the intrauterine development of heart
      diseases. The morphological changes in the thymic structure have been found to
      depend on the complicacy of the heart defect determining the degree of hypoxia.
      There are significant thymic structural changes manifesting themselves as
      disorders of the epithelial stroma. Its destruction areas exhibit activated
      fibroblastic differon that positively responds to vimentin and CD34. Increased
      resistance of lymphocytes to apoptosis has been ascertained and their
      proliferative properties determined. There is a progressive accumulation of the
      antiapoptotic protein Bcl-2 in the cytoplasm of thymocytes in the cortex of a
      thymic lobe and a decrease in Ki-67 expression in the lymphocytes in the thymic
      lobes, especially in cases of severe heart defects.

PMID- 24313186
TI  - [Early neonatal mortality in the Russian Federation in 2010].
AB  - The paper analyzes the data of the Federal State Statistics Service on early
      neonatal mortality in the Russian Federation as a whole and its federal districts
      in 2010. There was a steady decline (ranging from 6.52 to 2.75%) in the mean
      early neonatal mortality rates in the Russian Federation in 2000-2010. In 2010,
      there were low, moderate, and high early neonatal mortality rates in 59 (71.1%),
      20 (24.1%), 4 (4.8%) federal subjects, respectively. Most neonatal deaths were
      noted within the first 24 hours of life. According to the Federal State
      Statistics Service data, the commonest cause of early neonatal death in Russia is
      respiratory distress (103.2 deaths per 100,000 live births), hyaline membrane
      disease in particular. Among the causes of neonatal death, maternal diseases
      unrelated to pregnancy are indicated most commonly (in 22.7% of cases).

PMID- 24313187
TI  - [Testicular morphological changes in male alcohol abusers].
AB  - The sexual glands are highly sensitive to ethyl alcohol exposure. This study has
      investigated changes in the stroma and parenchyma of the testes in men who abuse
      alcohol. The sexual glands taken from 70 male alcohol abusers aged 25 to 60 years
      who were divided into groups according to the duration of alcoholic beverage
      consumption were examined. Pathomorphologic changes were found in the testicular
      structural components due to the progression of sclerotic stromal processes and
      functional parenchymal atrophy with long-term ethyl alcohol abuse.

PMID- 24313188
TI  - [Talc-induced pulmonary granulomas in drug addicts].
AB  - Among the diseases accompanied by granuloma formation in the lung, there is so
      called granulomatosis developing in injection drug users who have been long
      injecting suspensions of oral medications containing talc and other water
      insoluble fillers. 102 deaths of chronic intravenous drug users were examined; 12
      of whom showed pulmonary talc-induced granulomatosis. Their morphology was
      studied using polarized light microscopy. The main mechanisms of thanatogenesis
      in lethal cases within the first hours after intravenous injection of talc
      containing oral medication suspensions are explained.

PMID- 24313189
TI  - [Tissue responses to silicone materials in the body].
AB  - Light microscopy was used to study connective tissue capsules formed around
      different silicone breast implants. It has been found that due to the activity of
      microfibroblasts to minimize the volume of foreign bodies, the capsule gradually
      shrinks; its inner surface deforms and develops an undulating appearance with a
      multitude of outgrowths or protrusions inside. With the passage of time, silicone
      migrates to the capsule tissue and outside where it is absorbed by phagocytes.
      The inerter to a living organism the implant material is, the less it will
      stimulate a macrophage response. The task of designing new implants is to search
      for maximally bioinert materials that are strong enough to be compressed by the
      capsule and be fragmented and, moreover, elastically similar to normal breast
      tissue.

PMID- 24313190
TI  - [A rare case of glioblastoma metastasis to the lung].
AB  - The paper describes a case of metastatic glioblastoma in a 64-year-old woman who
      died in the early postoperative period after tumor removal. Lung metastases were
      diagnosed at autopsy. The tumor invading the superior sagittal sinus, a large
      venous reservoir shunting blood to the superior vena cava, was a factor
      contributing to extracranial extraneural hematogenous dissemination of the tumor
      in this case.

PMID- 24313191
TI  - [The present views of chronic obstructive pulmonary disease and the senile lung].
AB  - The gross postmortem diagnosis of chronic obstructive pulmonary disease (COPD)
      and its differential diagnosis with senile lungs on autopsy specimens are much
      difficult if clinical, X-ray, and functional findings are absent. The diagnosis
      of COPD is now possible only if medical history and clinical data, external
      respiratory function, and disease severity are considered and compared with the
      gross and microscopic autopsy pattern, by obligatorily evaluating the state of
      collagen and elastic fibers. Taking into account the current definition and
      essence of COPD, it is expedient to reconsider existing stereotypes in the
      postmortem diagnosis of this disease, by focusing our efforts on the study of its
      morphologic substrate, patho-, and morphogenesis.

PMID- 24313192
TI  - [Nosological profile of sudden cardiac death in athletes].
AB  - The review of the literature on sudden cardiac death in sport considers its main
      causes. The clinical and morphological characteristics are represented by the
      cardiac structure and electrophysiological pathology that causes sudden death in
      athletes.

PMID- 24313193
TI  - [New aspects of the pathogenesis and classification of basal-like breast
      carcinoma].
AB  - New approaches to the molecular classification of breast cancer are considered.
      Particular emphasis is placed on its basal-like type that belongs to the most
      aggressive and prognostically unfavorable forms of tumor. The origin of this type
      of breast cancer is the subject of intense debate in the scientific community.
      There are three basic theories that basal-like breast carcinoma may arise from
      the stem or myoepithelial cells and through dedifferentiation via epithelial
      mesenchymal transformation. The theory of its origin from stem/progenitor cells
      is most valid and proven.

PMID- 24313194
TI  - Specifics of breast cancer diagnosis in everyday practice.

PMID- 24313195
TI  - [Ya.L. Rapoport's pathomorphism study: the past and the present].
AB  - The paper considers problems in the study of the pathomorphism of human
      neoplasms.

PMID- 24313196
TI  - [On the name of our specialty].

PMID- 24313197
TI  - [Reinforce study on envirenmental impact on allergic rhinitis].

PMID- 24313198
TI  - [Prophylactic treatment for seasonal allergic rhinitis].

PMID- 24313199
TI  - [Insights into chronic inflammation in nasal mucosa].

PMID- 24313200
TI  - [Grading forecast research for pathogenesis of allergic rhinitis directed by
      meteorological elements].
AB  - OBJECTIVE: To analyze the correlation between meteorological factors and onset of
      allergic rhinitis (AR), and to establish the prediction of AR epideminlogical
      trend. METHODS: According to skin prick test (SPT) data of AR from Beijing
      Tongren Hospital and meteorological data of Beijing Observatory (2007 -2010) ,
      analyzed the relationship between meteorological factors and onset in patients
      with AR. To analyze the probability distribution of onset in AR patients, and
      establish the grade of AR epideminlogical trend index. SPSS 16. O software was
      used to analyze the data. RESULTS: The peak of onset in patients with AR appeared
      in 15 - 30 th August. There was significant correlation between the onset of AR
      patients and air temperature and vapor pressure(r = 0. 7473, F = 206. 13; r =0.
      8465, F = 321. 04; all P < 0. 001) , and the peak of air temperature and vapor
      pressure were one month earlier than the peak of onset AR patients in 4 years.
      According to the above correlation, nonlinear prediction models of AR were
      established; used probability grading method, onset index of AR was divided into
      4 grades. CONCLUSION: Index grade forecast of AR onset has important guiding
      significance for AR diagnosis and prophylaxis, offers objective reference
      information for health departments.

PMID- 24313201
TI  - [Expression of peripheral blood gammadelta T cells, treg cells and cytokines IL
      17 and TGF-beta1 in patients with allergic rhinitis].
AB  - OBJECTIVE: To investigate the expression of peripheral blood gammadelta T
      cells/CD4 CD25+ regulatory T cells(Treg) and cytokines interleukin 17 (IL-17) and
      transforming growth factor beta1 (TGF-beta1) in patients with allergic rhinitis.
      METHODS: From March 2012 to July 2012, 32 patients with allergic rhinitis (AR
      group) and 20 healthy control subjects (control group) were collected. The
      expression of peripheral blood gammadelta T cells/Treg cells were measured by
      flow cytometry and the levels of IL-17 and TGF-beta1 were evaluated by ELISA.
      SPSS 16.0 software was used to analyze the data. RESULTS: The percentages of
      gammadeltaT cells in AR group were (13.30 +/- 8.62)%, which was significantly
      higher (t = 5.18, P < 0.01) than those in control group (5.18 +/- 1.86)%. The
      percentages of Treg cells in AR group were (1.75 +/- 0.56)%, which were
      significantly lower (t = 7.46, P < 0. 01) than those in control group (4.76 +/-
      1.74)%. The IL-17 levels in AR group were (668.55 +/- 45.15) pg/ml, which were
      also significantly higher (t = 8.97, P < 0.01) than those in control group
      (573.53 +/- 17.42) pg/ml. The TGF-beta1 levels in AR group were (0.34 +/- 0.04)
      pg/ml, which were also significantly lower (t = 9.51, P < 0.01) than those in
      control group (0.49 +/- 0.06) pg/ml. There was a negative correlation between the
      percentages of gammadelta T cells and Treg cells (r = -0.561, P < 0.01). There
      was a negative correlation between the percentages of gammadelta T cells and TGF
      beta1 levels (r = -0.622, P < 0.01). A positive correlation was shown between the
      percentages of gammadelta T cells and IL-17 levels in AR (r = 0.469, P < 0.01). A
      positive correlation was shown between the percentages of Treg cells and TGF
      beta1 levels in AR (r = 0.738, P < 0.01). There was no correlation between IL-17
      levels and the percentages of Treg cells or TGF-beta1 levels (r value was -0.111,
      -0.196, all P > 0.05). CONCLUSION: There are imbalances of gammadelta T and Treg
      cells in peripheral blood of patients with allergic rhinitis. gammadelta T cells
      may be the main cell to produce IL-17, which may play an important role in
      allergic rhinitis.

PMID- 24313203
TI  - [A case with rare glottis foreign body].

PMID- 24313202
TI  - [Efficacy of sublingual immunotherapy with dermatophagoides farinae drops in
      monosensitized and polysensitized patients with allergic rhinitis].
AB  - OBJECTIVE: To compare the efficacy of sublingual immunotherapy (SLIT) with
      standardized Dermatophagoides farinae drops in monosensitized and polysensitized
      patients with allergic rhinitis. METHODS: The efficacy of SLIT in 69 patients who
      were sensitized to house dust mites and treated with Dermatophagoides farinae
      drops for 1.5-2.0 year with complete clinical data were analyzed retrospectively.
      These patients had been divided into the monoallergen sensitized group and
      polyallergen sensitized group according to the results of skin prick tests. The
      total medication score (TMS) and the total nasal symptoms score (TNSS) were
      evaluated before and half an year, 1.0 year and 1.5-2.0 years after SLIT
      treatment. RESULTS: After SLIT treatment for half an year, the TNSS in the
      monoallergen sensitized group (2.00 [1.00; 3.00]) was significantly lower than
      that in the polyallergen sensitized group (3.00 [2.00; 4.00], Z = -2.851, P <
      0.05), this significant difference of TNSS between the two groups was also found
      after SLIT treatment for 1.0 year (0.00 [0.00; 1.00], 2.00 [0.00; 3.00], Z = 
      2.590, P < 0.05). Whereas, there was no significant difference between the two
      groups after 1.5-2.0 years treatment refer to the TNSS (0.00 [0.00; 1.00], 0.00
      [0. 00; 2.00], Z = -1.461, P > 0.05). Half an year, 1.0 year and 1.5-2.0 years
      after SLIT treatment, the TMS in both groups reduced significantly, with no
      significant difference between two groups (Z value was - 0.777, -0.944, -0.907,
      all P > 0. 05). CONCLUSIONS: SLIT with Dermatophagoides farinae drops is
      effective in monosensitized and polysensitized patients with allergic rhinitis.
      And equivalent efficacy could be achieved after 1.5-2.years.

PMID- 24313204
TI  - [Anti-allergic effects of the probiotic preparations of enterococcus on
      experimental allergic rhinitis in mice].
AB  - OBJECTIVE: The aim of this study was to investigate the anti-allergic effects of
      lysozyme/heat-treated Enterococcus faecalis FK-23 (LFK) and heat-treated
      Enterococcus faecium sp. TN-3 (TN) on experimental allergic rhinitis (AR).
      METHODS: A total of twenty-four BALB/c mice were divided into four groups
      randomly: (1) positive control group, (2) LFK-fed group, (3) TN-fed group, and
      (4) negative control group. To establish the murine AR model, intraperitoneal
      injection and nasal drip with ovalbumin (OVA) were performed. Saline was used
      instead of OVA for negative control. Probiotic preparations of LFK and TN were
      orally administrated for 42 days [60 mg (0.5 ml)/d] in LFK-fed and TN-fed mice,
      respectively. The positive and negative control mice received saline orally for
      42 days. Nasal rubbing and sneezing were monitored on d 21, d 27, and d 35. After
      the final challenge, mice were sacrificed on d 42, and eosinophilic infiltration
      into the nasal mucosa was quantified (H&E stain). IFN-gamma, IL4 and OVA-specific
      IgE levels in the sera and splenocyte culture supernatants were determined by
      ELISA kits. RESULTS: Nasal rubbing of LFK-fed mice was significantly reduced
      compared to the positive control group on day 27 (t = 2.95, P = 0.028). Both in
      the LFK-fed and TN-fed mice, nasal rubbing (t value was 3.75 and 3.06, P value
      was 0.005 and 0.011, respectively) and sneezing (t value was 2.56 and 3.35, P
      value was 0.038 and 0. 01, respectively) were significantly decreased compared to
      the positive control group on d 35. The H&E strain section of nasal tissue showed
      that eosinophil influx into the nasal mucosa decreased significantly both in the
      LFK-fed and TN-fed mice compared to the positive control group on day 42 (t value
      was 3.44 and 2.97, P value was 0.014 and 0.025, respectively); however, the LFK
      fed mice and TN-fed mice had significant eosinophil influx into the nasal mucosa
      than that in the negative control group (t value was 2.54 and 3.39, P value was
      0.044 and 0.015, respectively). There were no significant differences in the
      serum levels of IL-4 and OVA-specific IgE, as well as the levels of IFN-gamma and
      IL-4 in splenocyte culture supernatants between the LFK-fed group and positive
      control group on d 42 (all P > 0.05). Interestingly, the TN-fed mice had
      significantly higher serum levels of IFN-gamma compared to the LFK-fed mice [TN
      fed mice: (27.07 +/- 3.83) pg/ml, LFK-fed mice: (14.83 +/- 0.99) pg/ml; Z = 2.49,
      P = 0.016], but not the negative control group [negative control group: (37.12 +/
      1.65) pg/ml; Z = 1.18, P = 0.343] on day 42. The serum levels of IL-4 were
      significantly lower in the TN-fed mice than those in the positive control group
      [TN-fed mice: (34.48 +/- 7.53) pg/ml, positive control group: (58.68 +/- 6.59)
      pg/ml; Z = 2.11, P = 0.035]; however, the levels were significantly higher in the
      TN-fed mice than those in the negative control group [negative control group:
      (20.22 +/- 1.75) pg/ml; Z = 2. 31, P = 0.021]. The TN-fed mice had significantly
      higher levels of IFN-gamma in splenocyte culture supernatants compared to the LFK
      fed mice (Z = 2.72, P = 0.03) and the positive control group (Z = 2.30, P =
      0.029), whilst the splenocyte culture supernatant levels of IL-4 (Z = 2.12, P =
      0.034) and the serum levels of OVA-specific IgE (Z = 2.31, P = 0.021) were
      significantly lower in the TN-fed mice compared to the positive control mice.
      CONCLUSIONS: It is suggested that oral administration of probiotic LFK or TN may
      alleviate nasal symptoms and reduce nasal eosinophilia in the murine AR model. TN
      supplementation has obviously regulatory effects on the cytokine levels of IFN
      gamma and IL-4, and significantly inhibitory effects on antigen-specific IgE
      levels.

PMID- 24313205
TI  - [Effect of neonatal immunization with different dosage allergen on the immunity
      of mice when grown up].
AB  - OBJECTIVE: To study the effect of neonatal immunization with different dosage
      allergen on the immunity of mice when grown. METHODS: Fifty neonatal BALB/c mice
      were divided into 4 groups randomly and subcutaneous injected with different
      dosage of ovalbumin (OVA) on day 1, 8 and 15 after born [NS group(10): injected
      with saline alone; NS + AL group (10): injected with saline and AL(OH)3; small
      dosage (SD) group (15): injected with 10 microg OVA and AL(OH)3; large dosage
      (LD) group (15): injected with 1000 microg OVA and AL(OH)3]. The mice were then
      challenged using caudal vein injection on 5 weeks old (NS group and NS + AL group
      were challenged with saline, SD group and LD group were challenged with 100
      microg OVA). The blood was collected 1 week later to examine OVA specific IgE,
      IgG1 and IgG2a. Mononuclear cells were drawn from the spleen and cultured.
      Concentration of IL-4, IFN-r, IL-10 was examined in the cultural supernatant.
      Flow cytometry was used to test the expression of CD4+ IL-4+, CD4+ IFN-gamma+,
      CD4 IL-10 cells. RESULTS: It was found that concentration of OVA specific IgE
      (OVA-sIgE) in SD group (0.33 +/- 0.18) was significantly higher than that of NS
      (0.07 +/- 0.01) and NS + AL (0.09 +/- 0.04) group (t value was -3.46 and -3.21,
      all P < 0.01), and LD group (0.17 +/- 0.10) as well (t = 2.58, P < 0.05). The
      concentration of OVA-sIgE was higher in LD group than that of NS group (t = 
      2.53, P < 0.05), but similar with that of NS + AL group (t = -2.04, P > 0.05).
      Both the concentration of OVA-sIgG1 and sIgG2a was higher in SD and LD group than
      that of NS and NS + AL group (all P < 0.05). The concentration of IL-4, IFN-gamma
      and IL-10 in the cultural supernatant of spleen mononuclear was all higher in SD
      group than that of NS and NS + AL group (all P < 0.01). The ratio of IFN-gamma/IL
      4 was significantly lower in SD group than that of NS and NS + AL group (t value
      was 2.14, 3.44, all P < 0.05), while the same ratio was higher in LD group than
      that of NS and NS + AL group (t value was -2.14, -1.61, all P < 0.05). Ratio of
      CD4+ IL-4+ cells was significant lower in LD group than that of SD group (P <
      0.05), while it was not different with that of NS and NS + AL group (P > 0. 05).
      CONCLUSION: Neonatal immunization with low dosage OVA could generate a specific
      immunity with Th2 direction, while with large dosage OVA could generate a
      specific immunity with Th1 direction.

PMID- 24313206
TI  - [Cervical tracheal resection with primary anastomosis for benign tracheal
      stricture in adult].
AB  - OBJECTIVE: To introduce the outcomes of tracheal resection with primary end to
      end anastomosis for benign cervical tracheal stenosis, and to discuss the
      strategy for prevention of surgical complications. METHODS: A retrospective
      analysis was performed in 12 patients diagnosed as benign cervical tracheal
      stenosis from October 2009 to June 2012. Laryngo-tracheal endoscopic examination
      and computed tomography (CT) were used to assess the degree of stenosis, the
      grade of inflammation and edema of the subglottis and trachea, and the extent of
      stenosis and the remaining linear amount of normal airway. The Meyer and Cotton
      grading system was used to categorise the clinical severity of the stenoses. All
      patients underwent tracheal resection with primary end to end anastomosis.
      RESULTS: The length of cervical tracheal stenosis ranged from 2.3 to 4.1 cm.
      Grade II stenosis was present in three patients, Grade III stenosis was present
      in seven patients and grade IV stenosis in two patients. Successful extubation
      was achieved in all 12 cases. After surgery, temporary hoarseness occurred in 1
      patient (8.3%); unilateral pulmonary atelectasis with pleural effusion occurred
      in 1 patient (8.3%); subcutaneous emphysema with infection occurred in 1 patient
      (8.3%); mild dysphagia occurred in 3 patients (25.0%); a slight deepening of the
      tone of voice occurred in 5 patients (41.7%), granulation tissue growth near the
      suture occurred in 3 patients (25.0%), and suture dehiscence did not occur in any
      patient. The follow-up period ranged from 6 months to 38 months, no patient
      developed restenosis. CONCLUSIONS: It presents a high success rate and good
      functional result of tracheal resection with primary end-to-end anastomosis.
      Therefore, it is an effective and reliable approach for the management of benign
      cervical tracheal stenosis. To avoid complications, the preoperative assessment,
      patients selection and postoperative management should be emphasized.

PMID- 24313207
TI  - [Treatments of oropharyngeal anterior wall cancer by transhyoid surgery
      radiotherapy].
AB  - OBJECTIVE: To evaluate the transhyoid resection of oropharyngeal anterior wall
      cancer and oncological outcomes of the surgery combined with radiotherapy.
      METHODS: A total of 24 cases with carcinoma located in the anterior wall of
      oropharynx was reviewed. The TNM stages were as follows: T2 in 7 cases, T3 in 2
      cases, T4 in 15 cases; NO in 7 cases, N1 in 4 cases, N2 in 12 cases and N3 in 1
      case. Tumor resection was performed via transhyoid approach, including 9 cases
      with partial glossectomy + partial laryngectomy, 7 cases with partial glossectomy
      + total laryngectomy, 7 cases with total glossectomy + partial laryngectomy and 1
      case with partial glossectomy alone pectoralis major myocutaneous flaps were
      applied to repair synchronously the defects of tongue and lateral pharyngeal wall
      in 16 cases and the defect of cervical skin in 1 case. Radial forearm free flap
      and sternohyoid myocutaneous flap were used to repair the defect of tongue and
      lateral and posterior pharyngeal wall in 1 case. Sternohyoid myocutaneous flap
      was applied to reconstruct the tongue base in 2 cases. Bilateral and unilateral
      neck dissections were performed in 20 cases and 4 cases respectively. Five cases
      received preoperative radiotherapy and 16 cases received postoperative
      radiotherapy. RESULTS: All cases had negative surgical margin. Pathological
      examination showed neck lymph metastasis in 17 cases (70.8%). Three patients had
      postoperative pharyngocutaneous fistula. Two of them who underwent partial
      glossectomy + total laryngectomy and pectoralis major myocutaneous flaps
      synchronously reconstruction suffered from pharyngocutaneous fistula 4 days after
      operation. The fistula was closed by re-suturation following debridement and 2
      weeks dressing change. The other one who underwent partial glossectomy + partial
      laryngectomy suffered from pharyngocutaneous fistula during postoperation
      radiotherapy and healed by the pectoralis major myocutaneous repair. Tracheostomy
      tubes were removed within 1-6 months, with good voice and swallowing functions,
      in 16 of 17 cases who underwent partial laryngectomy. Another one failed to pull
      out tracheotomy tube because of dyspnea. Twenty one cases were followed up over 3
      years and Kaplan-Meier survival analysis showed the 3-year overall survival rate
      was 72.6%. CONCLUSIONS: The transhyoid tumor resection is an effective surgical
      approach for oropharyngeal anterior wall cancer. The defect following tumor
      resection is commonly need repair synchronously with various flaps. Acceptable
      outcome could be received by surgery combined with radiotherapy.

PMID- 24313208
TI  - [Investigation on biological characteristics of CD133+ cancer stem cells in human
      laryngeal carcinoma Hep-2 cell line].
AB  - OBJECTIVE: To investigate the biology characters of CD133+ cancer stem cells from
      Hep-2 cell line. METHODS: The Flow cytometry was applied to purify CD133+ cells
      from Hep-2 cell line. The sorted CD133+ cells were cultured in RPMI1640. The
      ability of migration, invasion and clonality of CD133+ cells were performed to
      characterize the properties of the cells. CD133+ cells and CD133- control cells
      were treated with paclitaxel and exposed respectively to X-rays emitted by linear
      accelerator with a dose of 10 Gy. The surviving rates and growth inhibition ratio
      of cells in two groups were detected with MTT assay to observe the resistance to
      irradiation and chemotherapy in CD133+ cells. RESULTS: The percentage of CD133+
      cells in the unsorted and the sorted cells were 3.1% +/- 0.2% and 90.2% +/- 5.5%,
      respectively. CD133+ cells showed the higher proliferation and colony ability
      than CD133- cells. The numbers of CD133+ and CD133- cells that passed the
      membrane of Transwell chamber were 526 +/- 39 and 220 +/- 20 respectively (t =
      22.08, P < 0.001). The colony forming units of three passages were 30.0% +/-
      4.7%, 32.2% + 3.6%, 32.7% + 3.4% in CD133 cells and 15.2% +/- 2.2%, 12.0% + 2.5%,
      13.8% +/- 3.3% in CD133- cells. There were statistic difference between two
      groups (t = 8.99, t = 14.66, t = 12.69, P < 0.01). At 24, 48, and 72 hours of
      treatment with paclitaxel, the cell surviving rates of CD133+ cells were 90.1% +/
      5.9%, 85.1% +/- 7.1% and 70.3% +/- 6.4% and lower than those of CD133- cells,
      respectively (t = 5.24, t = 8.18, t = 8.14, P < 0.01) . After radiotherapy,
      growth inhibition ratio of CD133+ and CD133- cells were 30.0% +/- 7.1% and 55.0%
      +/- 6.3% (t = 8.30, P < 0.01). CONCLUSIONS: CD133+ cells exist in a small
      proportion in Hep-2 cell line and they show the properties of cancer stem cells,
      with the resistance to irradiation and chemotherapy.

PMID- 24313209
TI  - [Math1 gene therapy for kanamycin and furosemide-induced deaf guinea pigs].
AB  - OBJECTIVE: To observe the morphology and function changes of cochlear hair cells
      before and after math1 gene injection into the cochlea of deaf guinea pigs which
      were induced by kanamycin and furosemide. To explore the feasibility of Math1
      gene for medicine-induced deafness therapy. METHODS: Kanamycin (500 mg/kg) and
      furosemide (50 mg/kg) were given to the healthy adult guinea pigs intramuscularly
      and intravenously to establish the deafness model. The guinea pigs whose auditory
      brainstem response (ABR) threshold > 95 dB SPL were randomly divided into five
      groups. Blank control group (without any treatment, n = 3), operation control
      group (right ear scala tympani operation, n = 3), artificial perilymph group
      (right ear scala tympani injection artificial perilymph, n = 3), virus vector
      group [right ear scala tympani injection adenovirus which carrying enhanced green
      fluorescent protein (EGFP) gene (Ad. EGFP) , n = 4], Math1 gene therapy group
      [right ear scala tympani injection adenovirus which carrying Math1 and EGFP gene
      (Ad. Math1-EGFP), n = 6]. Each animal received ABR test before and after
      injection. The cochlear tissue was observed by scanning electronic microscopy.
      RESULTS: The ABR thresholds of tone burst( 4, 8, 16, 20 kHz ) were not
      statistically significant in different groups (P > 0.05). The number of hair
      cells increased in some of severe deaf guinea pigs after the injection of Ad.
      Math1-EGFP gene. However, there was no obvious difference with morphology and
      numbers of cochlea hair cells in other groups. CONCLUSIONS: The injection of
      Math1 gene to cochlea can regenerate or repair the hair cells of medicine-induced
      deaf guinea pigs, but there was no improvement on the hearing loss.

PMID- 24313210
TI  - [Endoscopic coblation assisted arytenoidectomy in the treatment of bilateral
      vocal cord paralysis].
AB  - OBJECTIVE: To introduce a new surgical technique for the treatment of bilateral
      vocal cord paralysis. METHODS: Twenty-nine patients with bilateral vocal cord
      paralysis treated in Dalian Municipal Central Hospital between 2008 and 2012 were
      retrospectively studied. Coblation assisted arytenoidectomy was performed in all
      cases. The pre and postoperative glottic measurement and vocal acoustic
      parameters were analyzed. RESULTS: All patients were decanulated 1 week after
      operation. Three months later, the mean glottic area increased from (21.9 +/-
      4.7) to (40.3 +/- 5.2) mm2 (t = 5.74. P < 0.05); the width of maximal glottic
      chink increased from (1.47 +/- 0.37) to (4.82 +/- 0.54) mm (t = 6.24, P < 0.05).
      Twenty-six patients (89.7%) satisfied with the voice quality. Acoustic parameters
      (F0, jitter, shimmer) were no significant difference (P > 0. 05) , but there was
      a significant difference in maximum phonation time (P < 0.05). During three
      months to 3.5 years follow-up, the patients had a stable airway and effective
      phonation. CONCLUSIONS: Endoscopic coblation assisted arytenoidectomy is a new
      surgical method for the treatment of patients with bilateral vocal cord
      paralysis, which is efficient, minimally invasive and safe.

PMID- 24313211
TI  - [Fourth branchial abnormity and management experiences].
AB  - OBJECTIVE: To investigate the fourth branchial abnormity and its managements.
      METHOD: Twelve cases of the fourth branchial abnormity treated between January
      2005 and April 2012 were reviewed. RESULTS: Dissection of the recurrent laryngeal
      nerve was done in all cases. Partial thyroidectomy was performed in 10 cases, and
      2 cases of them received selective neck dissection including level II, III, IV
      and VI. The abnormity lesions were found to pass posterior to the thyroid glands
      in the 10 cases and to pass through the inferior constrictor muscle into the
      pyriform sinus in 7 cases of them. The internal opening in the pyriform sinus
      demonstrated by preoperative examination couldn't be identified in the operation
      in one case. The abnormity tract terminated at the lateral surface of the
      esophagus in one case, passed into the cervical esophagus in one case, and
      terminated at the lateral surface of the thyroid gland in one case, and formed a
      cyst lateral to the thyroid gland in one case. No abnormity tract was found to
      loop around the hypoglossal nerve and to descend into the mediastinum. The left
      recurrent laryngeal nerve was cut off in one patient, although end to end
      anastomosis was performed immediately, the patient was still complicated with
      left vocal cord paralysis postoperatively. The median follow-up time of the cases
      was 24 months (8-88 months). One case was lost of follow up. No recurrence was
      found in 10 cases. Recurrence was found in one case, and no recurrence in 10
      cases. CONCLUSIONS: The presentation of congenital the fourth branchial fistula
      is variated significantly. Most abnormity lesions had close relations to the
      thyroid gland and the recurrent laryngeal nerve, thus the recurrent laryngeal
      nerve need to protect and partial thyroidectomy might be considered. In the
      recurrent cases when the abnormity couldn't be identified clearly, selective neck
      dissection including level II, III, IV and VI should be done long term follow up
      should be carried out in the cases that the internal opening couldn't be found.

PMID- 24313212
TI  - [Clinical analysis of hypothyroidism hoarseness defective diagnosis].

PMID- 24313213
TI  - [Misdiagnosis of cervical bronchogenic cyst with nodular goiter in a case].

PMID- 24313214
TI  - [Cutaneous horn on the head and cheek: report of four cases].

PMID- 24313215
TI  - [Epigenetic regulation: a new field in allergic rhinitis].

PMID- 24313216
TI  - [Probiotics in the prevention and treatment of allergic diseases].

PMID- 24313217
TI  - [An introduction of inhalation therapy].

PMID- 24313218
TI  - Biomimetic choline-like graphene oxide composites for neurite sprouting and
      outgrowth.
AB  - Neurodegenerative diseases or acute injuries of the nervous system always lead to
      neuron loss and neurite damage. Thus, the development of effective methods to
      repair these damaged neurons is necessary. The construction of biomimetic
      materials with specific physicochemical properties is a promising solution to
      induce neurite sprouting and guide the regenerating nerve. Herein, we present a
      simple method for constructing biomimetic graphene oxide (GO) composites by
      covalently bonding an acetylcholine-like unit (dimethylaminoethyl methacrylate,
      DMAEMA) or phosphorylcholine-like unit (2-methacryloyloxyethyl phosphorylcholine,
      MPC) onto GO surfaces to enhance neurite sprouting and outgrowth. The resulting
      GO composites were characterized by Fourier-transform infrared spectroscopy, X
      ray photoelectron spectroscopy, Raman spectroscopy, UV-vis spectrometry, scanning
      electron microscopy, and contact angle analyses. Primary rat hippocampal neurons
      were used to investigate nerve cell adhesion, spreading, and proliferation on
      these biomimetic GO composites. GO-DMAEMA and GO-MPC composites provide the
      desired biomimetic properties for superior biocompatibility without affecting
      cell viability. At 2 to 7 days after cell seeding was performed, the number of
      neurites and average neurite length on GO-DMAEMA and GO-MPC composites were
      significantly enhanced compared with the control GO. In addition, analysis of
      growth-associate protein-43 (GAP-43) by Western blot showed that GAP-43
      expression was greatly improved in biomimetic GO composite groups compared to GO
      groups, which might promote neurite sprouting and outgrowth. All the results
      demonstrate the potential of DMAEMA- and MPC-modified GO composites as biomimetic
      materials for neural interfacing and provide basic information for future
      biomedical applications of graphene oxide. 

PMID- 24313219
TI  - Synthesis of 2-N/S/C-substituted benzothiazoles via intramolecular cyclative
      cleavage of benzotriazole ring.
AB  - The synthesis of numerous 2-N/S/C-substituted benzothiazoles was achieved from
      substituted thiocarbonylbenzotriazoles via free-radical intramolecular cyclative
      cleavage of the benzotriazole ring in the presence of (TMS)3SiH and AIBN under
      mild conditions. The developed methodology demonstrates significant compatibility
      under microwave conditions and is important as it avoids the use of toxic metals
      for radical cyclization. 

PMID- 24313220
TI  - Melatonin prevents experimental preterm labor and increases offspring survival.
AB  - Preterm delivery is the leading cause of neonatal mortality and contributes to
      delayed physical and cognitive development in children. At present, there is no
      efficient therapy to prevent preterm labor. A large body of evidence suggests
      that intra-amniotic infections may be a significant and potentially preventable
      cause of preterm birth. This work assessed the effect of melatonin in a murine
      model of inflammation-associated preterm delivery which mimics central features
      of preterm infection in humans. For this purpose, preterm labor was induced in
      BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS)
      at 10.00 hr (10 MUg LPS) and 13.00 hr (20 MUg LPS) on day 15 of pregnancy. On day
      14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted
      into a group of animals. In the absence of melatonin, a 100% incidence of preterm
      birth was observed in LPS-treated animals, and the fetuses showed widespread
      damage. By comparison, treatment with melatonin prevented preterm birth in 50% of
      the cases, and all pups from melatonin-treated females were born alive and their
      body weight did not differ from control animals. Melatonin significantly
      prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2alpha, and
      cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced
      increase in uterine nitric oxide (NO) production, inducible NO synthase protein,
      and tumor necrosis factor-alpha (TNFalpha) levels. Collectively, our results
      suggest that melatonin could be a new therapeutic tool to prevent preterm labor
      and to increase offspring survival.

PMID- 24313221
TI  - Reply to: Cancer inflammation and inflammatory biomarkers: can neutrophil,
      lymphocyte, and platelet counts represent the complexity of the immune system?

PMID- 24313222
TI  - Preparation of a particle-loaded membrane for trace gas sampling.
AB  - A divinylbenzene (DVB) particle-loaded membrane with high extraction capacity was
      prepared using the bar coating method. The prepared membrane was evaluated in
      terms of morphology, effect of particle ratio, and membrane size on extraction
      efficiency, as well as linear calibration curve and limit of detection. The SEM
      (scanning electron microscope) images showed that the DVB particles were
      uniformly distributed in the PDMS base, ensuring the repeatability of the
      membranes. The extraction amount was quantified by gas chromatography-mass
      spectrometry coupled with a thermal desorption unit. Results showed that the
      extraction efficiency of the prepared membrane increased about 2 orders of
      magnitude for benzene sampling as the particle ratio increased from 0% to 30%,
      and the extraction amount was linearly proportional to the size of the membrane.
      A comparison with a pure PDMS membrane and DVB/PDMS fiber for outdoor air
      sampling showed that the extraction efficiency of the DVB/PDMS membrane was
      significantly enhanced, especially for volatile and polar compounds. The limit of
      detection was about 0.03 ng/mL for benzene in air, and the linear dynamic range
      extended to 100 ng/mL. An equilibrium calibration method was proposed for low
      level air pollutant sampling using this high capacity membrane, and a
      displacement effect was not observed. To demonstrate the power of the technique,
      the developed approach was applied to monitor both spot and time weighted average
      (TWA) concentrations of benzene in outdoor air. A high spot concentration of
      benzene was observed in morning and afternoon rush hours, with TWA concentrations
      of 10.7 ng/L measured over the 11-h monitoring period. 

PMID- 24313223
TI  - Juxtaposition of automatic mode switching and tachycardia-terminating algorithms
      in a dual-chamber implantable cardioverter defibrillator.

PMID- 24313224
TI  - Improved survival in myeloma patients: starting to close in on the gap between
      elderly patients and a matched normal population.
AB  - The outcome for multiple myeloma patients has improved since the introduction of
      bortezomib, thalidomide and lenalidomide. However, studies comparing new and
      conventional treatment include selected patient groups. We investigated
      consecutive patients (n = 1638) diagnosed in a defined period and compared
      survival with a gender- and age-matched cohort Swedish population (n = 9 340
      682). Median overall survival for non-high-dose treated patients was 2.8 years.
      The use of bortezomib, thalidomide or lenalidomide in first line therapy
      predicted a significantly longer overall survival (median 4.9 years) compared to
      conventional treatment (2.3 years). Among non-high-dose treated patients
      receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and
      63% have survived at 3 and 5 years as compared to 48% and 22% with conventional
      drugs and 88% and 79% in the matched cohort populations, respectively. The median
      overall survival in high-dose treated patients was 6.9 years. Of these patients,
      84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the
      matched cohort population. Overall survival in the best non-high-dose treated
      outcome group is closing the gap with the matched cohort. Upfront use of new
      drugs is clearly better than waiting until later lines of treatment. 

PMID- 24313225
TI  - Rapid, scalable assembly of stereochemically rich, mono- and bicyclic acyl
      sultams.
AB  - A one-pot, sequential protocol is reported that involves complementary ambiphile
      pairing (CAP) of a vinyl sulfonamide with a variety of unprotected amino acids
      via aza-Michael addition and subsequent intramolecular amidation. The method
      generates diverse, sp(3)-rich mono- and bicyclic acyl sultams in a highly
      scalable manner. Modular pairing of stereochemically rich building blocks allows
      quick access to all possible isomers. Extension to include one-pot, sequential 3
      , 4-, and 5-multicomponent protocols is also discussed. 

PMID- 24313226
TI  - Experimental results of a residential house fire test on tenability: temperature,
      smoke, and gas analyses.
AB  - A fire experiment conducted in a British 1950s-style house is described.
      Measurements of temperature, smoke, CO, CO2 , and O2 were taken in the Lounge,
      stairwell, and front and back bedrooms. The front bedroom door was wedged open,
      while the door to the back bedroom was wedged closed. Contrary to expectations
      and despite the relatively small fire load, analysis and hazard calculations show
      permeation of toxic fire gases throughout the property with lethal concentrations
      of effluent being measured at each sampling point. A generally poor state of
      repair and missing carpets in the upper story contributed to a high degree of gas
      and smoke permeation. The available egress time was calculated as the time before
      the main escape route became impassable. Given known human responses to fire,
      such an incident could have caused fatalities to sleeping or otherwise immobile
      occupants. 

PMID- 24313228
TI  - Avian malaria in New Zealand.
AB  - Avian malaria parasites of the genus Plasmodium have the ability to cause
      morbidity and mortality in naive hosts, and their impact on the native
      biodiversity is potentially serious. Over the last decade, avian malaria has
      aroused increasing interest as an emerging disease in New Zealand with some
      endemic avian species, such as the endangered mohua (Mohua ochrocephala), thought
      to be particularly susceptible. To date, avian malaria parasites have been found
      in 35 different bird species in New Zealand and have been diagnosed as causing
      death in threatened species such as dotterel (Charadrius obscurus), South Island
      saddleback (Philesturnus carunculatus carunculatus), mohua, hihi (Notiomystis
      cincta) and two species of kiwi (Apteryx spp.). Introduced blackbirds (Turdus
      merula) have been found to be carriers of at least three strains of Plasmodium
      spp. and because they are very commonly infected, they are likely sources of
      infection for many of New Zealand's endemic birds. The spread and abundance of
      introduced and endemic mosquitoes as the result of climate change is also likely
      to be an important factor in the high prevalence of infection in some regions and
      at certain times of the year. Although still limited, there is a growing
      understanding of the ecology and epidemiology of Plasmodium spp. in New Zealand.
      Molecular biology has played an important part in this process and has markedly
      improved our understanding of the taxonomy of the genus Plasmodium. This review
      presents our current state of knowledge, discusses the possible infection and
      disease outcomes, the implications for host behaviour and reproduction, methods
      of diagnosis of infection, and the possible vectors for transmission of the
      disease in New Zealand. 

PMID- 24313227
TI  - Mechanism and site of inhibition of AMPA receptors: pairing a thiadiazole with a
      2,3-benzodiazepine scaffold.
AB  - 2,3-Benzodiazepine compounds are synthesized as drug candidates for treatment of
      various neurological disorders involving excessive activity of AMPA receptors.
      Here we report that pairing a thiadiazole moiety with a 2,3-benzodiazepine
      scaffold via the N-3 position yields an inhibitor type with >28-fold better
      potency and selectivity on AMPA receptors than the 2,3-benzodiazepine scaffold
      alone. Using whole-cell recording, we characterized two thiadiazolyl compounds,
      that is, one contains a 1,3,4-thiadiazole moiety and the other contains a 1,2,4
      thiadiazole-3-one moiety. These compounds exhibit potent, equal inhibition of
      both the closed-channel and the open-channel conformations of all four homomeric
      AMPA receptor channels and two GluA2R-containing complex AMPA receptor channels.
      Furthermore, these compounds bind to the same receptor site as GYKI 52466 does, a
      site we previously termed as the "M" site. A thiadiazole moiety is thought to
      occupy more fully the side pocket of the receptor site or the "M" site, thereby
      generating a stronger, multivalent interaction between the inhibitor and the
      receptor binding site. We suggest that, as a heterocycle, a thiadiazole can be
      further modified chemically to produce a new class of even more potent,
      noncompetitive inhibitors of AMPA receptors. 

PMID- 24313229
TI  - Diabetes nurse educators' experiences of providing care for women, with
      gestational diabetes mellitus, from disadvantaged backgrounds.
AB  - AIMS AND OBJECTIVES: To explore diabetes nurse educators' experiences of
      providing care for women, with gestational diabetes mellitus, from disadvantaged
      backgrounds and to gather information which would assist with the development of
      an educational programme that would support both women and diabetes educators.
      BACKGROUND: Rates of gestational diabetes mellitus have increased dramatically in
      recent years. This is concerning as gestational diabetes mellitus is linked to
      poorer pregnancy outcomes including hypertension, stillbirth, and nursery
      admission. Poorest outcomes occur among disadvantaged women. gestational diabetes
      mellitus is also associated with maternal type 2 diabetes and with child obesity
      and type 2 diabetes among offspring. Effective self-management of gestational
      diabetes mellitus reduces these risks. Diabetes nurse educators provide most
      education and support for gestational diabetes mellitus self-management. DESIGN:
      An interpretative phenomenological analysis approach, as espoused by Smith and
      Osborn (Qualitative Psychology: A Practical Guide to Research Methods, 2008,
      Sage, London, 51), provided the framework for this study. METHODS: The views of
      six diabetes educators were explored through in-depth interviewing. Interviews
      were transcribed verbatim and analysed according to steps outlined by Smith and
      Osborn (Qualitative Psychology: A Practical Guide to Research Methods, 2008,
      Sage, London, 51). RESULTS: Three themes emerged from the data: (1) working in a
      suboptimal environment, (2) working to address the difficulties and (3) looking
      to the future. Throughout, the diabetes nurse educators sought opportunities to
      connect with women in their care and to make the educational content
      understandable and meaningful. CONCLUSIONS: Low literacy among disadvantaged
      women has a significant impact on their understanding of gestational diabetes
      mellitus information. In turn, catering for women with low literacy contributes
      to increased workloads for diabetes nurse educators, making them vulnerable to
      burnout. RELEVANCE TO CLINICAL PRACTICE: There is a need for targeted educational
      programmes for women with low literacy. Resources should be literacy appropriate,
      with photographs and simple text, and include culturally appropriate foods and
      information. This approach should lead to an improvement in the women's uptake of
      gestational diabetes mellitus information and may lead to a lessening of the
      workload burden for diabetes nurse educators.

PMID- 24313230
TI  - Lessons learned from the microbial analysis of the Herschel spacecraft during
      assembly, integration, and test operations.
AB  - Understanding microbial diversity in spacecraft assembly clean rooms is of major
      interest with respect to planetary protection considerations. A coordinated
      screening of different clean rooms in Europe and South America by three German
      institutes [Deutsches Zentrum fur Luft- und Raumfahrt (DLR), Leibniz-Institut
      DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ), and the
      Institute of Microbiology and Archaea Center, University of Regensburg] took
      place during the assembly, test, and launch operations of the Herschel spacecraft
      in 2006-2009. Through this campaign, we retrieved critical information regarding
      the microbiome within these clean rooms and on the Herschel spacecraft, which
      served as a model for upcoming ESA mission preparations. This "lessons learned"
      document summarizes and discusses the data we obtained during this sampling
      campaign. Additionally, we have taken the opportunity to create a database that
      includes all 16S rRNA gene sequences ever retrieved from molecular and cultivable
      diversity studies of spacecraft assembly clean rooms to compare the microbiomes
      of US, European, and South American facilities.

PMID- 24313231
TI  - Two new alkaloids from the bulbs of Lycoris sprengeri.
AB  - Two new alkaloids, lycosprenine (1) and 2alpha-methoxy-6-O-methyllycorenine (2),
      along with 22 known alkaloids (3-23b), were isolated from the bulb of Lycoris
      sprengeri. Their structures were elucidated on the basis of spectral analysis and
      by comparison of the spectroscopic data with those of known compounds. Selected
      compounds (1-3 and 6-9) were tested for their neuroprotective activities against
      H2O2-, CoCl2- and Abeta25-35-induced SH-SY5Y cell injury, most of which exhibited
      neuroprotective effects of different degrees. 

PMID- 24313233
TI  - Variations in the efficacy of resistant maltodextrin on body fat reduction in
      rats fed different high-fat models.
AB  - Many studies have utilized a variety of methods to induce obesity in rodents, but
      they often received inconsistent results. The present study intended to use
      resistant maltodextrin (RMD) as a means to investigate the variations in its
      efficacy on body fat accumulation under the influence of four high-fat (HF)
      models of 23% or 40% total fat, comprising soybean oil, lard, and/or condensed
      milk. Results indicated that integrating condensed milk into the diets could help
      increase diet intake, boost energy intake, increase weight gain, and enhance fat
      formation. Supplementation of RMD (2.07 g/kg) notably reduced total body fat
      levels in three HF models, with the exception of a condensed-milk-added 40%-fat
      diet that may have misrepresented the functions of RMD. The uses of the 23% HF
      diets, with and without milk, and the milk-free 40% HF diet were therefore
      recommended as suitable models for antiobesity evaluations of RMD, or other fiber
      rich products. 

PMID- 24313235
TI  - Cannabis use among treatment-seeking smokers: motives and the moderating effects
      of anxiety sensitivity.
AB  - BACKGROUND AND OBJECTIVES: Concurrent use of cannabis and tobacco is associated
      with poor tobacco cessation outcomes. As little research has examined why
      treatment-seeking tobacco users engage in cannabis use, the objective of this
      study was to discover if emotional vulnerability and cannabis use motives are
      associated with concurrent users' cannabis use. METHODS: One hundred thirty-eight
      (n = 138) daily cigarette smokers seeking smoking cessation treatment completed
      measures of anxiety sensitivity, cannabis use motives, and cannabis use. RESULTS:
      Stronger coping, enhancement, social, and expansion motives were associated with
      using greater amounts of cannabis per use occasion. In a model accounting for all
      these motives, anxiety sensitivity moderated the relationship between enhancement
      motives and cannabis use. DISCUSSION AND CONCLUSIONS: Clinical interventions for
      concurrent tobacco-cannabis users may be advanced by targeting low anxiety
      sensitive individuals' use of cannabis to increase excitement and fun. Such an
      approach may consist of having clients identify and engage in healthier
      pleasurable activities and by teaching clients to accept the trade-off between
      perceived less pleasurable, but healthier activities and cannabis use.

PMID- 24313234
TI  - Dysregulation of diurnal cortisol secretion affects abstinence induction during a
      lead-in period of a clinical trial for depressed cocaine-dependent patients.
AB  - BACKGROUND AND OBJECTIVE: Hypothesizing that stress dysregulation may worsen
      cocaine dependence, we investigated the effect of diurnal cortisol secretion
      profile, suppression of cortisol secretion, and total cortisol secretion on
      retention, abstinence-based voucher earnings, days of cravings, and mood status
      of participants at the end of a 2-week medication-free lead-in prior to
      randomization in a clinical trial of mirtazapine (60 mg vs. placebo) for
      depressed cocaine-dependent patients. METHODS: We measured saliva cortisol levels
      at 9 AM, 2 PM, and 5 PM on the first two consecutive days of a 2-week medication
      free lead-in period. Results from saliva samples were used to estimate the total
      daily level of cortisol, the diurnal profile of secretion (typical vs. atypical),
      and response to dexamethasone suppression (.1 mg). Seventy-seven patients
      collected saliva samples at baseline, and 65 (85%) were suitable for profile
      analysis. RESULTS: Patients with typical profiles (52%) collected significantly
      more abstinence-based voucher earnings during the lead-in (U = 299.50, p = .025).
      Diurnal secretion profile did not significantly affect mood status, days of
      craving, or retention. There were no significant effects of suppression of
      cortisol secretion or of total cortisol levels on any outcome measures.
      CONCLUSION: In a subgroup of cocaine-dependent patients, deviation of cortisol
      secretion away from the homeostatic diurnal pattern was associated with reduced
      success at achieving early abstinence, an important determinant of treatment
      success.

PMID- 24313236
TI  - Biochemical marker of use is a better predictor of outcomes than self-report
      metrics in a contingency management smoking cessation analog study.
AB  - BACKGROUND AND OBJECTIVES: This investigation compared cotinine (primary
      metabolite of nicotine) at study intake to self-report metrics (e.g., Fagerstrom
      Test of Nicotine Dependence [FTND]) and assessed their relative ability to
      predict smoking outcomes. METHODS: We used data from an analog model of
      contingency management for cigarette smoking. Non-treatment seeking participants
      (N = 103) could earn money in exchange for provision of a negative carbon
      monoxide (CO) sample indicating smoking abstinence, but were otherwise not
      motivated to quit. We used intake cotinine, FTND, percent of friends who smoke,
      and years smoked to predict longitudinal CO and attendance, time-to-first
      positive CO submission, and additional cross-sectional outcomes. RESULTS: Intake
      cotinine was consistently predictive (p < .05) of all outcomes (e.g.,
      longitudinal CO and attendance, 100% abstinence, time-to-first positive CO
      sample), while years smoked was the only self-report metric that demonstrated any
      predictive ability. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Cotinine could be
      more informative for tailoring behavioral treatments compared to self-report
      measures.

PMID- 24313237
TI  - The course of sleep disturbances in early alcohol recovery: an observational
      cohort study.
AB  - INTRODUCTION: Understanding the course and determinants of sleep disturbances in
      alcoholic patients may help identify patients at high risk of persistent sleep
      problems, relapse and guide treatment interventions. METHODS: We prospectively
      administered the Pittsburgh Sleep Quality Index (PSQI) to all patients (N = 196)
      admitted to a 1-month residential treatment program. Our analysis excluded
      patients with active drug abuse/dependence. Demographic data, psychiatric
      diagnoses, Patient Health Questionnaire-9 (PHQ-9), Alcohol Use Disorders
      Identification Test (AUDIT) and Inventory of Drug Taking Situations (IDTS) scores
      were obtained. Univariate and logistic regression analyses were performed using
      sex, age, hazardous alcohol use, PHQ-9 scores, hypnotic use, and use of alcohol
      as a hypnotic as correlates to admission PSQI scores and improvement in PSQI
      scores. RESULTS: A total of 119 alcoholic patients met inclusion criteria (mean
      age 50.6 +/- 13.2 years). The rates of sleep disturbances at admission and
      discharge were 69.3% and 49.1%, respectively. Self report of using alcohol to
      fall asleep and use of hypnotics were associated with elevated PSQI scores. Total
      PSQI scores improved over 4 weeks (p < .001). Change in PSQI scores was not
      effected by gender, use of hypnotics, hazardous alcohol use, use of alcohol as a
      hypnotic or co-morbid psychiatric diagnosis. Older age predicted improvement in
      PSQI scores in patients with sleep disturbances (p = .004). CONCLUSION: While a
      large proportion of alcoholics had sleep disturbances upon admission and at
      discharge from a residential treatment program, only older age was associated
      with improvements in sleep disturbances during early alcohol recovery.

PMID- 24313238
TI  - Concurrent substance abuse is associated with sexual risk behavior among adults
      seeking treatment for prescription opioid dependence.
AB  - BACKGROUND: Increasingly, new HIV infections among people who use drugs are
      attributed to sexual risk behavior. However, HIV prevention research targeting
      persons with opioid dependence continues to focus on drug injection practices.
      Moreover, despite the rising prevalence of prescription opioid dependence in the
      United States, little is known about HIV risk in this population. METHODS: This
      study examined the prevalence of sexual risk behavior among patients with opioid
      dependence who primarily use prescription opioids for non-medical purposes. As
      part of a multi-site clinical trial, participants (N = 653) completed a baseline
      assessment that included the Risk Behavior Survey. RESULTS: In the past month,
      74% were sexually active. Of these, most had opposite sex partners (97.3%) and
      vaginal intercourse (97.1%); anal intercourse was uncommon (3.1%). The majority
      reported unprotected intercourse (76.5%), but few had multiple partners (11.3%).
      Unprotected intercourse was associated with history of other substance dependence
      (adjusted odds ratio [AOR] = 1.73), and having multiple partners was associated
      with concurrent cocaine use (AOR = 2.54). Injection drug use in the past month
      was rare (2.5%). CONCLUSIONS: While the majority of sexually active participants
      engaged in unprotected intercourse, the proportion with multiple sex partners was
      low relative to other samples of persons who use illicit drugs. Among persons
      with non-medical prescription opioid dependence, those who concurrently use other
      substances may be at elevated risk for HIV infection. Comprehensive assessment of
      substance abuse history among individuals dependent upon prescription opioids is
      critical for identifying patients who may require additional clinical
      interventions to reduce HIV sexual risk behavior.

PMID- 24313239
TI  - Effects of HCV seropositive status on buprenorphine pharmacokinetics in opioid
      dependent individuals.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to examine the effect of
      hepatitis C virus (HCV) infection on buprenorphine pharmacokinetics in opioid
      dependent, buprenorphine/naloxone-maintained adults. METHODS: A retrospective
      analysis of buprenorphine pharmacokinetics in HCV seropositive and seronegative
      buprenorphine/naloxone-maintained individuals (N = 49) was undertaken. RESULTS:
      Relative to HCV seronegative subjects, HCV seropositive subjects had higher
      buprenorphine exposure, as demonstrated by elevated buprenorphine AUC and Cmax
      values (p = .03 and .02, respectively) and corresponding elevations in the
      metabolites, buprenorphine-3-glucuronide AUC values (p = .03) and
      norbuprenorphine-3-glucuronide AUC and C24 values (p = .05 and .03,
      respectively). DISCUSSION AND CONCLUSIONS: HCV infection was associated with
      higher plasma concentrations of buprenorphine and buprenorphine metabolites.
      SCIENTIFIC SIGNIFICANCE AND FUTURE DIRECTIONS: Findings suggest the potential for
      opioid toxicity among HCV-infected patients treated with buprenorphine/naloxone,
      and possible hepatotoxic effects related to increased buprenorphine exposure. HCV
      infected patients receiving buprenorphine may need lower doses to maintain
      therapeutic plasma concentrations.

PMID- 24313240
TI  - Associations among pain, non-medical prescription opioid use, and drug overdose
      history.
AB  - BACKGROUND AND OBJECTIVE: Recently, use of prescription opioids (POs) has
      increased; non-medical PO (NMPO) use is linked to overdose. NMPO use is common
      among individuals prescribed opioids for pain, and those in substance use
      disorder (SUD) treatment with pain could be at increased risk for unintentional
      overdose due to NMPO use. We examined associations between pain, NMPO use, and
      overdose among SUD treatment patients. METHODS: Among 342 patients at a
      residential SUD treatment center, logistic regression examined the association of
      overdose with pain, adjusting for substance use, suicide attempts, and
      demographics. RESULTS: Pain was positively related to NMPO use. Heroin use,
      suicide attempts, pain, and NMPO use were positively associated with overdose;
      but NMPO use attenuated the pain-overdose relationship. CONCLUSIONS: The
      relationship between pain and overdose among substance users may be, in part,
      explained by the association between pain and heavy NMPO use.

PMID- 24313241
TI  - Serum biochemical parameters following heroin withdrawal: an exploratory study.
AB  - BACKGROUND: Long-term consumption of opioid compounds, even after withdrawal,
      affects serum biochemical parameters. Investigating these alterations is a new
      approach in substance abuse studies. METHOD: This study investigated clinical
      laboratory results in men who are currently active, recently abstinent and non
      heroin users. Participants (N = 240) of this matched cohort study included heroin
      dependent men referred for abstinence treatment, volunteer men who did not abuse
      opioids matched for age, sex, body mass index, and educational level (control
      group). The groups were further sub-divided for analysis into (a) continuous
      heroin users for more than 2 years (N = 70), the dependent group; (b) heroin
      abusers with 1 month abstinence period (N = 70), identified as ex-heroin
      dependents; and (c) a matched, non-dependent control group (N = 100). All
      participants were tested for fasting blood sugar (FBS), sodium, potassium,
      calcium, uric acid (UA), blood urea nitrogen (BUN), creatinine, total
      cholesterol, triglycerides (TGs), total protein, fibrinogen, and prothrombin.
      RESULTS: Compared to the control group, ex-heroin dependents showed decreased FBS
      and significantly higher sodium, creatinine, and cholesterol levels. Compared to
      the heroin dependent group, the ex-heroin dependents showed significant
      differences in FBS, sodium, calcium, creatinine, UA, and thrombin time. No
      significant differences were noted between ex-heroin dependents and controls in
      potassium, calcium, UA, BUN, TGs, total protein, and thrombin time. CONCLUSION:
      These results demonstrate altered laboratory markers in long-term heroin
      dependents as well as ex-heroin dependents and suggest the need for further
      identification, population distribution, and etiological understanding of these
      biomarkers in individuals who have abused heroin.

PMID- 24313243
TI  - Predictive factors for relapse in patients on buprenorphine maintenance.
AB  - BACKGROUND AND OBJECTIVES: Despite the dramatic increase in the use of
      buprenorphine for the treatment of opioid dependence, clinical outcomes of this
      treatment approach continue to need evaluation. This study examines factors
      associated with relapse and retention during buprenorphine treatment in a sample
      of opioid dependent outpatients. METHODS: In a retrospective chart review of 62
      patients with opioid dependence, relapse was determined by self-report, urine
      toxicology screens, and by checking the state controlled substance monitoring
      database. Data was analyzed using two-way tests of association and logistic
      regression. RESULTS: Patients with comorbid anxiety disorders, active
      benzodiazepine use (contrary to clinic policy), or active alcohol abuse, were
      significantly more likely to relapse. Patients who relapsed were also more likely
      to be on a higher buprenorphine maintenance dose. CONCLUSION: This study
      identifies relapse risk factors during buprenorphine treatment for opioid
      dependence. Future research is needed to determine whether modifying these
      factors may lead to improved treatment outcomes.

PMID- 24313242
TI  - Trauma exposure predicts alcohol, nicotine, and drug problems beyond the
      contribution of PTSD and depression in patients with cardiovascular disease: data
      from the Heart and Soul Study.
AB  - BACKGROUND AND OBJECTIVES: This study examined the role of lifetime trauma
      exposure in a longitudinal study of adults with cardiovascular disease to
      determine the unique contribution of trauma exposure to risk for drug and alcohol
      problems and smoking. METHODS: Data were drawn from the Heart and Soul Study, a
      prospective cohort study designed to determine the mechanisms of associations
      between psychological factors and increased risk of cardiovascular events in high
      risk patients (n = 1,022). RESULTS: Lifetime exposure to a higher number of
      trauma types predicted substance use outcomes beyond risk explained by PTSD and
      depression. In addition, across trauma types, interpersonal traumas were most
      strongly associated with substance use problems. CONCLUSIONS: Our results suggest
      that, though PTSD and depression play a role in the association between trauma
      exposure and substance use, many other factors also contribute; therefore
      focusing on these psychological comorbidities alone is not sufficient. SCIENTIFIC
      SIGNIFICANCE: The integration of mental health care and/or case management
      support with primary and specialty medical care may improve detection and
      treatment for patients with substance use and comorbid mental and physical health
      problems. Screening for trauma exposure is an important part of good clinical
      care.

PMID- 24313244
TI  - A randomized, double-blind, placebo-controlled trial of venlafaxine for the
      treatment of depressed cocaine-dependent patients.
AB  - OBJECTIVE: This study tested the hypothesis that the antidepressant venlafaxine
      would be an effective treatment for cocaine abusers with concurrent depressive
      disorders. METHODS: This was a randomized, 12-week, double-blind, placebo
      controlled trial of outpatients (N = 130) meeting DSM-IIIR criteria for cocaine
      dependence and major depression or dysthymia (by SCID interview). Participants
      were treated with venlafaxine, up to 300 mg/day versus placebo. All patients
      received weekly individual manual-guided relapse prevention therapy. Weekly
      outcome measures included Clinical Global Impression Scale (CGI), self-reported
      cocaine use, urine toxicology and the Hamilton Depression Scale (Ham-D). RESULTS:
      Mood response, defined as a 50% reduction in the Ham-D between randomization and
      end of study, was 41% (26/64) on venlafaxine, and 33% (22/66) on placebo (p =
      .39). Measures of depression (Ham-D and CGI) improved more rapidly on venlafaxine
      than placebo, but these differences disappeared by weeks 6-8. Cocaine outcomes
      did not differ between treatment groups, and the proportion of patients achieving
      three or more consecutive weeks of urine-confirmed abstinence was low
      (venlafaxine: 16%; placebo: 15%). Reduction in cocaine use was associated with
      mood response. CONCLUSIONS: Overall, venlafaxine was not superior to placebo on
      either mood or cocaine use outcomes. Mood improvement was associated with
      improvement in cocaine use. However, placebo mood response was only moderate, and
      the proportion of patients achieving sustained abstinence was low. This suggests
      that the subgroup of cocaine-dependent patients with depressive disorders is
      relatively treatment resistant, and that further research is needed to improve
      outcomes for these patients.

PMID- 24313245
TI  - Does experiencing homelessness affect women's motivation to change alcohol or
      drug use?
AB  - BACKGROUND AND OBJECTIVES: Homeless women are at high risk of drug and alcohol
      dependence and may receive less opportunity for treatment. Our objective was to
      examine the association between experiencing homelessness and motivation to
      change drug or alcohol use. METHODS: Women (n = 154) participants in a study of
      substance dependence at an urban medical center (69 with some homeless days in
      the last 90 days; 85 continuously housed at baseline) completed six items rating
      motivation to change alcohol or drug use (ie, importance, readiness, and
      confidence) at baseline and in 3-, 6-, and 12-month follow-up interviews.
      Unadjusted and longitudinal analyses controlling for covariates (eg,
      demographics, insurance status, substance use consequences, mental health status,
      and participation in treatment) were conducted. RESULTS: There were no
      significant differences between women experiencing homeless days versus
      continuously housed women in the odds of reporting high motivation to change
      alcohol or drug use, either in unadjusted baseline analyses or longitudinal
      analyses adjusted for covariates. Covariates that were significantly associated
      with high importance, readiness or confidence to change behavior were higher life
      time consequences of substance use, and participation in 12-step programs.
      DISCUSSION AND CONCLUSIONS: The findings suggest that clinicians should not make
      assumptions that homeless women have low motivation to change their substance
      use. SCIENTIFIC SIGNIFICANCE AND FUTURE DIRECTIONS: The same opportunities for
      addiction treatment should be offered to homeless as to housed women.

PMID- 24313246
TI  - Associations between post-traumatic stress symptoms, stimulant use, and treatment
      outcomes: a secondary analysis of NIDA's Women and Trauma study.
AB  - BACKGROUND AND OBJECTIVES: To examine the associations between post-traumatic
      stress disorder (PTSD) symptoms, stimulant use, and treatment outcomes among
      dually diagnosed women. METHODS: Participants were 141 women who participated in
      a multisite clinical trial of group treatments for PTSD and addictions. RESULTS:
      Generalized linear models indicated Seeking Safety (SS; a cognitive-behavioral
      intervention) was significantly more effective than Women's Health Education
      (WHE; a control group intervention) in reducing stimulant use at follow-up among
      women who were heavy stimulant users at pre-treatment and who showed improvements
      in PTSD symptoms. There were no significant differences between the interventions
      among women who were light stimulant users at treatment entry. CONCLUSIONS AND
      SCIENTIFIC SIGNIFICANCE: These findings suggest that integrated treatment of co
      occurring PTSD and addictions may be more effective than general health education
      approaches for heavy stimulant users. Assessment of frequency of stimulant use
      among individuals with PTSD symptoms may inform treatment selection for this
      population.

PMID- 24313247
TI  - Alcohol use following an alcohol challenge and a brief intervention among alcohol
      dependent individuals.
AB  - BACKGROUND AND OBJECTIVES: The study examined the effects of an alcohol challenge
      on naturalistic drinking among alcohol-dependent individuals and explored brief
      motivational interviewing (MI) as a potential intervention for these
      participants. METHOD: Alcohol-dependent individuals (n = 32, eight females)
      completed the intake assessment, alcohol challenge, one MI session, and 1-month
      follow-up (87.5% retention) where they completed measures of drinking and
      motivation for change. RESULTS: As expected, multilevel mixed models revealed
      that drinking did not increase post-alcohol challenge. Participants reported a
      reduction in ambivalence, drinking days, and a trend towards fewer total drinks
      between the MI and 1-month follow-up. CONCLUSIONS: Consistent with other studies,
      the alcohol challenge did not worsen alcohol use. Results support further
      investigation of brief MI for alcohol-dependent participants in alcohol
      challenges. SCIENTIFIC SIGNIFICANCE: Alcohol administration to alcohol-dependent
      participants appears to not exacerbate naturalistic drinking. MI may be a
      feasible intervention for non-treatment seeking alcohol-dependent participants in
      alcohol challenge studies.

PMID- 24313248
TI  - Smoking cessation recruitment messages tailored to African American high school
      smokers.

PMID- 24313249
TI  - Improved electrocatalytic ethanol oxidation activity in acidic and alkaline
      electrolytes using size-controlled Pt-Sn nanoparticles.
AB  - The promotion of the electrocatalytic ethanol oxidation reaction (EOR) on
      extended single-crystal Pt surfaces and dispersed Pt nanoparticles by Sn under
      acidic conditions is well known. However, the correlation of Sn coverage on Pt
      nanoparticle electrocatalysts to their size has proven difficult. The reason is
      that previous investigations have typically relied on commercially difficult to
      reproduce electrochemical treatments of prepared macroscopic electrodes to adsorb
      Sn onto exposed Pt surfaces. We demonstrate here how independent control over
      both Sn coverage and particle size can yield a significant enhancement in EOR
      activity in an acidic electrolyte relative to previously reported
      electrocatalysts. Our novel approach uses electroless nanoparticle synthesis
      where surface-adsorbed Sn is intrinsic to Pt particle formation. Sn serves as
      both a reducing agent and stabilizing ligand, producing particles with a narrow
      particle size distribution in a size range where the mass-specific
      electrocatalytic activity can be maximized (ca. 1-4 nm) as a result of the
      formation of a fully developed Sn shell. The extent of fractional Sn surface
      coverage on carbon-supported Pt nanoparticles can be systematically varied
      through wet-chemical treatment subsequent to nanoparticle formation but prior to
      incorporation into macroscopic electrodes. EOR activity for Pt nanoparticles is
      found to be optimum at a fractional Sn surface coverage of ca. 0.6. Furthermore,
      the EOR activity is shown to increase with Pt particle size and correlate with
      the active area of available Pt (110) surface sites for the corresponding Sn-free
      nanoparticles. The maximum area- and mass-specific EOR activities for the most
      active catalyst investigated were 17.9 MUA/cm(2)Pt and 12.5 A/gPt, respectively,
      after 1 h of use at 0.42 V versus RHE in an acidic electrolyte. Such activity is
      a substantial improvement over that of commercially available Pt, Pt-Sn, and Pt
      Ru alloy catalysts under either acidic or alkaline conditions. 

PMID- 24313250
TI  - The influence of mucosal tissue thickening on crestal bone stability around bone
      level implants. A prospective controlled clinical trial.
AB  - OBJECTIVE: To evaluate how bone-level implants maintain crestal bone stability
      after thickening of thin mucosal tissues with allogenic membrane. MATERIALS AND
      METHODS: Ninety-seven bone-level implants of 4.1 mm diameter (Institute Straumann
      AG, Switzerland) were evaluated in 97 patients (28 men and 69 women, mean age
      47.3 +/- 1.2 years). According to vertical gingival thickness, patients were
      assigned into test T1 (thin, 2 mm or less, n = 33), test T2 (thin thickened with
      allogenic membrane, n = 32) and control C groups (thick, more than 2 mm, n = 32).
      Implants were placed in posterior mandible in one-stage approach and after
      integration were restored with single screw-retained metal-ceramic restorations.
      Radiographic examination was performed after implant placement, 2 months after
      healing, after prosthetic restoration and after 1-year follow-up. Crestal bone
      loss was calculated mesially and distally. Mann-Whitney U-test was applied and
      significance was set to 0.05. RESULTS: After 2 months, implants in group T1 had
      0.75 +/- 0.11 mm bone loss mesially and 0.73 +/- 0.10 mm distally. Implants in
      group T2 had 0.16 +/- 0.06 mm mesially and 0.20 +/- 0.06 mm distally. C group
      implants lost 0.17 +/- 0.05 mm mesially and 0.18 +/- 0.03 mm distally.
      Differences between T1/T2, and T1/C were statistically significant (P = 0.000)
      both mesially and distally, while between T2 and C was not significant mesially
      (P = 0.861) and distally (P = 0.827). After 1-year follow-up implants in group T1
      had 1.22 +/- 0.08 mm bone loss mesially and 1.14 +/- 0.07 mm distally. Implants
      in group T2 had 0.24 +/- 0.06 mm mesially and 0.19 +/- 0.06 mm distally. C group
      implants lost 0.22 +/- 0.06 mm mesially and 0.20 +/- 0.06 mm distally.
      Differences between T1/T2, and T1/C were statistically significant (P = 0.000)
      both mesially and distally, while between T2 and C was not significant mesially
      (P = 0.909) and distally (P = 0.312). CONCLUSIONS: Significantly less bone loss
      can occur around bone-level implants placed in naturally thick mucosal tissues,
      in comparison with thin biotype. Augmentation of thin soft tissues with allogenic
      membrane during implant placement could be way to reduce crestal bone loss.

PMID- 24313251
TI  - LGBT aging: the contributions of community-based research.

PMID- 24313252
TI  - Social care networks and older LGBT adults: challenges for the future.
AB  - Research on service needs among older adults rarely addresses the special
      circumstances of lesbian, gay, bisexual, and transgender (LGBT) individuals, such
      as their reliance on friend-centered social networks or the experience of
      discrimination from service providers. Limited data suggests that older LGBT
      adults underutilize health and social services that are important in maintaining
      independence and quality of life. This study explored the social care networks of
      this population using a mixed-methods approach. Data were obtained from 210 LGBT
      older adults. The average age was 60 years, and 71% were men, 24% were women, and
      5% were transgender or intersex. One-third was Black, and 62% were Caucasian.
      Quantitative assessments found high levels of morbidity and friend-centered
      support networks. Need for and use of services was frequently reported. Content
      analysis revealed unmet needs for basic supports, including housing, economic
      supports, and help with entitlements. Limited opportunities for socialization
      were strongly expressed, particularly among older lesbians. Implications for
      senior programs and policies are discussed. 

PMID- 24313253
TI  - Investigating the needs and concerns of lesbian, gay, bisexual, and transgender
      older adults: the use of qualitative and quantitative methodology.
AB  - Extensive research on the specific needs and concerns of lesbian, gay, bisexual,
      and transgender (LGBT) older adults is lacking. This article describes the
      results of both quantitative studies (i.e., LGBT Elders Needs Assessment Scale)
      and qualitative studies (i.e., focus groups and in-depth interviews with lesbian,
      gay, or bisexual [LGB] older adults and LGB grandparents) that specifically
      sought to investigate the unique needs and concerns of LGBT elders. The results
      identified 7 areas (medical/health care, legal, institutional/housing, spiritual,
      family, mental health, and social) of concern and the recognition that the needs
      and concerns of LGBT older adults be addressed across multiple domains, rather
      than in isolation. 

PMID- 24313254
TI  - Friends, family, and caregiving among midlife and older lesbian, gay, bisexual,
      and transgender adults.
AB  - The study examines the frequency and nature of the informal caregiving experience
      for midlife and older lesbian, gay, bisexual, or transgender (LGBT) adults.
      Responses from a Twin Cities Metropolitan Area LGBT aging needs assessment survey
      were analyzed for social supports, current caregiving activity and availability
      of a caregiver. The majority of respondents identified a primary caregiver who
      was not a legal relation; and compared to the general population were (a) less
      likely to have traditional sources of caregiver support and (b) more likely to be
      serving as a caregiver and caring for someone to whom they were not legally
      related. Implications of the findings for enhancing resources to more fully
      support the 10% of caregivers that are caring for non-kin are discussed. 

PMID- 24313255
TI  - The Greater St. Louis LGBT Health and Human Services Needs Assessment: an
      examination of the Silent and Baby Boom generations.
AB  - This study sought to understand differences and similarities between lesbian,
      gay, bisexual, and transgender (LGBT) Baby Boomers and members of the Silent
      generation in the greater St. Louis region in relation to perceived barriers to
      service use, LGBT identity disclosure, experiences of violence and victimization,
      and mental health. An online survey was completed by 118 Baby Boomers and 33
      Silents. Baby Boomers were found to perceive more barriers to health care and
      legal services, have fewer legal documents in place, feel less safe in their
      communities, and have experienced an increased rate of verbal harassment compared
      to their predecessors. Differences may be attributed to higher levels of LGBT
      identity disclosure among Baby Boomers across their lifetime. These findings
      support the current work of Services and Advocacy for GLBT Elders Metro St.
      Louis, with implications for other communities, and shed light on the need for
      continued advancement in the development and implementation of programs as LGBT
      Baby Boomers age. 

PMID- 24313256
TI  - Aging out in the desert: disclosure, acceptance, and service use among midlife
      and older lesbians and gay men.
AB  - Lesbian, gay, bisexual, and transgender (LGBT) persons in the county of
      Riverside, CA and in the Palm Springs/Coachella Valley area, in particular,
      responded to a questionnaire addressing concerns about identity disclosure and
      comfort accessing social services. Distributed at a Pride festival, as well as
      through religious, social, and service agencies, the final sample for analysis of
      502 comprised 401 (80%) gay men and 101 (20%) lesbians in 4 groups: < 50 years of
      age (18%), 50 to 59 (26%), 60 to 69 (36%), and over 70 (20%). Results reveal that
      almost one-third of midlife and older gay men and lesbians maintain some fear of
      openly disclosing their sexual orientation. Along comparable lines with similar
      proportions, older gay men and lesbians maintain some discomfort in their use of
      older adult social services, even as the majority reports that they would feel
      more comfortable accessing LGBT-friendly identified services and programs. In
      both cases, lesbians reported greater fear and discomfort than did gay men; older
      gay men and lesbians reported that they would be less comfortable accessing LGBT
      identified services and programs than did younger gay men and lesbians. These
      data support prior research on the apprehension of LGBT elders in accessing care,
      the crucial role of acceptance, with some suggestions of how social services
      might better prepare to address these needs. 

PMID- 24313257
TI  - Aging out: a qualitative exploration of ageism and heterosexism among aging
      African American lesbians and gay men.
AB  - African Americans elders, like their non-African American counterparts, are not a
      homogeneous group; however an early characteristic placed on all African
      Americans is in their shared history in the United States. As members of multiple
      minority groups, older lesbian, gay, bisexual, and transgender (LGBT) people of
      African descent have survived racism, heterosexism, homophobia, and now ageism.
      This article describes a qualitative study grounded in Black feminist and
      minority stress theories that explored the issues of perceived social
      discrimination and alienation of 15 older African American lesbians and gay males
      whose lived experiences were captured using in-depth, face-to-face interviews.
      Several themes were identified in the study, including (a) Sense of Alienation in
      the African American Community, (b) Deliberate Concealment of Sexual Identity and
      Orientation, (c) Aversion to LGBT Labels, (d) Perceived Discrimination and
      Alienation From Organized Religion, (e) Feelings of Grief and Loss Related to
      Aging, (f) Isolation, and (g) Fear of Financial and Physical Dependence. The
      implication of the findings suggests that the ethos and needs of older African
      American lesbian women and gay men need to be addressed to eliminate potential
      barriers to successful aging for this cohort. 

PMID- 24313258
TI  - Service utilization among older adults with HIV: the joint association of sexual
      identity and gender.
AB  - This study examines the association of sexual identity and gender among older
      clients with HIV at an AIDS service organization using the Andersen Model. Data
      confirm those aging with HIV exhibit high rates of age-associated illnesses 10 to
      20 years before expected. They have fragile social networks that cannot supply
      the informal supports needed. This aging population will need to increasingly
      access community-based services. Sexual identity and gender were weak covariates
      of service utilization. Although heterosexual men used more services, utilization
      was largely predicted by service needs and the use of case management.
      Implications for service delivery and policy are discussed. 

PMID- 24313259
TI  - Do LGBT aging trainings effectuate positive change in mainstream elder service
      providers?
AB  - This study aims to provide empirical evidence regarding whether attitudes,
      beliefs, and intentions of elder-service providers can be positively affected as
      a result of attending cultural competency training on the unique challenges of
      sexual and gender minorities. Stigmatization throughout the lifespan may have a
      causal influence on barriers to care, social isolation, and concomitant health
      disparities. Data were collected for this study at 4 Massachusetts training
      events to pilot a cultural competency workshop on lesbian, gay, bisexual, and
      transgender (LGBT) aging for mainstream elder service providers. This quasi
      experimental study included the analysis of pre- and posttest surveys completed
      by the service-provider attendees (N = 76). The analytic strategy included
      descriptive statistics, paired t tests, chi-square analyses, and repeated
      measures analyses of variance. Findings revealed statistically significant
      improvement in numerous aspects of providers' knowledge, attitudes, and
      behavioral intentions subsequent to the training sessions. These included (p =
      .000) awareness of LGBT resources, policy disparities, spousal benefits for same
      sex couples, and the intention to challenge homophobic remarks. This study
      concludes that mainstream elder-service provider training on LGBT aging issues
      results in positive change. Recommendations include long-term follow up of
      participants, the inception of agency-level surveys to appraise institutional
      culture change, and increased curriculum on transgender older adults. 

PMID- 24313260
TI  - Persistent erythema multiforme associated with Epstein-Barr virus infection.
AB  - Erythema multiforme (EM) is a common, self-limiting condition. Recurrent EM is a
      well-recognised variant, often associated with herpes simplex virus infection. It
      is frequently managed with prophylactic aciclovir. Anecdotal reports suggest that
      recurrent EM may be associated with the use of corticosteroids. Persistent EM,
      however, is a rare variant, with few cases reported in the literature. It has a
      protracted course often with atypical and inflammatory lesions. It has been
      associated with occult viral infections, particularly Epstein-Barr Virus (EBV),
      as well as inflammatory bowel disease and malignancy. We report a case of EM
      associated with EBV infection. 

PMID- 24313261
TI  - Decreased plasma IL-22 levels and correlations with IL-22-producing T helper
      cells in patients with new-onset systemic lupus erythematosus.
AB  - Interleukin-22 (IL-22) and IL-22-producing T helper (Th) cells are involved in
      the pathogenesis of autoimmune diseases. However, the roles of IL-22 and IL-22
      producing T helper cells in systemic lupus erythematosus (SLE) remain unclear.
      Plasma levels of IL-22 were measured in 41 patients with SLE (19 new-onset and 22
      relapsing patients) and 20 healthy controls by enzyme-linked immunosorbent assay
      (ELISA). Meanwhile, the percentages of CD4(+) IFN-gamma(+) (Th1), CD4(+) IL-17(+)
      (Th17) and CD4(+) IFN-gamma(-) IL-17(-) IL-22(+) (Th22) cells in peripheral
      lymphocytes were determined by flow cytometry, and plasma IL-22 autoantibodies
      were detected by ELISA in 19 new-onset SLE patients and 20 healthy controls.
      Plasma IL-22 levels in new-onset SLE patients were significantly decreased
      compared with relapsing SLE patients and healthy controls. After treatment with
      prednisone and hydroxychloroquine, the levels of plasma IL-22 in new-onset SLE
      patients were obviously increased but still lower than healthy controls. There
      was a positive correlation between plasma IL-22 levels and the percentages of
      Th22 cells, but not Th1 and Th17 cells. Moreover, plasma IL-22 levels as well as
      peripheral Th17 and Th22 cells correlated with SLE disease activity index
      (SLEDAI) scores and erythrocyte sedimentation rate (ESR). High frequencies of
      plasma IL-22 autoantibodies were detected in new-onset SLE patients. However, IL
      22 levels did not correlate with IL-22 autoantibody. Decreased plasma IL-22
      levels and correlation with Th22 cells may be distinct features in new-onset SLE.
      Moreover, IL-22 and Th22 cell correlated with SLE disease activity. 

PMID- 24313262
TI  - The distribution and anthelmintic resistance status of Trichostrongylus
      colubriformis, T. vitrinus and T. axei in lambs in New Zealand.
AB  - AIM: To determine the distribution of the three common Trichostrongylus spp.
      infecting sheep and their resistance status on farms throughout New Zealand,
      using PCR. METHODS: Cultures were prepared from faecal samples from 70 farms
      while conducting faecal egg count reduction tests (FECRT) in lambs between 2010
      and 2012. Trichostrongylus-type infective stage larvae (L3) were recovered from
      cultures, derived from untreated control and albendazole-, levamisole- and
      ivermectin-treated groups of lambs on each of the farms involved, and these were
      identified to species using PCR analysis of the second internal transcribed
      spacer region of ribosomal DNA. The species composition of the larvae present in
      cultures from the untreated control groups was examined across all farms to
      assess any potential differences in geographical distribution. In addition, the
      species composition of larvae cultured from the untreated and anthelmintic
      treated lamb groups were compared to determine which species exhibited resistance
      to each of the anthelmintics used in the FECRT. RESULTS: Of 67 farms with
      Trichostrongylus spp. present, 42 (63%) cultures from the untreated control
      groups contained all three Trichostrongylus spp. and no significant geographical
      patterns in their distribution were detected. Seven samples contained only one
      species. Irrespective of the anthelmintic efficacy levels, Trichostrongylus
      colubriformis dominated cultures prepared from lambs following treatment with
      albendazole (99.1 (95%CI = 97-100)% of larvae) or levamisole (81.6 (95%CI = 75.3
      87.9)% of larvae), indicating the presence of widespread resistance in this
      species. In cultures prepared from levamisole-treated lambs, small numbers of T.
      axei larvae were also frequently present (5.4 (95% CI = 1.3-12.4)% of larvae).
      Resistance to ivermectin was not found in any of the three Trichostrongylus spp.
      after PCR identification. Although larvae were identified, based on length, as
      being Trichostrongylus spp., for 24 of the 48 samples cultured following
      treatment with ivermectin, 100% of the larvae present were identified as
      Teladorsagia circumcincta. CONCLUSIONS: As in previous surveys, all three
      Trichostrongylus spp. were common throughout New Zealand and no geographical
      patterns were detected in the current study. On all farms where resistance to
      albendazole and/or levamisole was indicated (i.e. efficacy <95%), the species
      identified as being resistant was T. colubriformis. Even where efficacies were
      >95%, T. colubriformis still tended to dominate in post-treatment cultures. While
      this could reflect a lower susceptibility of T. colubriformis to these
      anthelmintics, it seems more likely to indicate the presence of resistant
      genotypes in these populations. Similarly, T. axei also tended to be present
      after treatment with levamisole, which likely reflects a known lower
      susceptibility of this species to these anthelmintics.

PMID- 24313263
TI  - Synthesis of three OSW-1 analogs with maltose side chains bearing different
      protection groups.
AB  - In order to simplify the synthesis of OSW-1's disaccharide side chain and explore
      the structure-activity relationship of OSW-1, three 16alpha-O-maltose OSW-1
      analogs carrying three maltose side chains bearing different protections were
      designed and synthesized. 

PMID- 24313264
TI  - Simultaneous determination of capilliposide B and capilliposide C in rat plasma
      by LC-MS/MS and its application to a PK study.
AB  - BACKGROUND: Lysimachia capillipes Hemsl (Primulaceae), a folk medicinal plant in
      China, showed significant anti-tumor activity in recent studies. A reliable LC
      MS/MS method was developed and validated for the simultaneous determination of
      capilliposide B and capilliposide C, the major bioactive components in this
      plant, in rat plasma. RESULTS: Rat plasma and whole blood samples were pretreated
      with dichlorvos, an esterase inhibitor, minimizing degradation of analytes in
      biological samples. The method validation was conducted over the curve range of
      10.0 to 5000 ng/ml for both analytes. The intra- and inter-day precision and
      accuracy of the QC samples showed <=6.1% RSD and 1.3-3.7% relative error.
      CONCLUSION: The method was successfully applied to determine the concentrations
      of capilliposide B and capilliposide C in incurred rat plasma samples, after
      administration of Lysimachia capillipes Hemsl extract for a rat PK study.

PMID- 24313265
TI  - When being narrow minded is a good thing: locally biased people show stronger
      contextual cueing.
AB  - Repeated contexts allow us to find relevant information more easily. Learning
      such contexts has been proposed to depend upon either global processing of the
      repeated contexts, or alternatively processing of the local region surrounding
      the target information. In this study, we measured the extent to which observers
      were by default biased to process towards a more global or local level. The
      findings showed that the ability to use context to help guide their search was
      strongly related to an observer's local/global processing bias. Locally biased
      people could use context to help improve their search better than globally biased
      people. The results suggest that the extent to which context can be used depends
      crucially on the observer's attentional bias and thus also to factors and
      influences that can change this bias. 

PMID- 24313266
TI  - Immunotherapy for recurrent ovarian cancer: a further piece of the puzzle or a
      striking strategy?
AB  - INTRODUCTION: Treatment of ovarian cancer has been long standardized with the
      inclusion of surgery and chemotherapy based on platinum and taxanes, this
      strategy reaching high remission rates. However, when this treatment fails,
      further options are available with little benefit. Since ovarian cancer has
      specific immunologic features, actually immunotherapy is under evaluation to
      overcome treatment failure in patients experiencing recurrence. AREAS COVERED:
      Immunogenicity of ovarian cancer and its relationship with clinical outcomes is
      briefly reviewed. The kinds of immunotherapeutic strategies are summarized. The
      clinical trials investigating immunotherapy in recurrent ovarian cancer patients
      are reported. EXPERT OPINION: The results of these clinical trials about
      immunotherapy are interesting, but little clinical benefit has been achieved
      until now. For this reason, we could conclude that immunotherapy is quite
      different from other treatment options and it could change the global approach
      for recurrent ovarian cancer treatment. However, to date only fragmentary
      findings are available to define the real role of immunotherapy in this setting.

PMID- 24313269
TI  - Alternative techniques for left ventricular pacing in cardiac resynchronization
      therapy.
AB  - Cardiac resynchronization therapy (CRT) is an important treatment modality for a
      well-defined subgroup of heart failure patients. Coronary sinus (CS) lead
      placement is the first-line clinical approach but the insertion is unsuccessful
      in about 5-10% of the patients. In recent years, the number of CRT recipients and
      the considerable need for left ventricular (LV) lead revisions increased
      enormously. Numerous techniques and technologies have been specifically developed
      to provide alternatives for the CS LV pacing. Currently, the surgical access is
      most frequently used as a second choice by either minithoracotomy or especially
      the video-assisted thoracoscopy. The transseptal or transapical endocardial LV
      lead implantations are being developed but there are no longer follow-up data in
      larger patient cohorts. These new techniques should be reserved for patients
      failing conventional or surgical CRT implants. In the future, randomized studies
      are needed to asses the potential benefits of some alternative LV pacing
      techniques and other new technologies for LV lead placement are expected. 

PMID- 24313270
TI  - Atrazine-based self-assembled monolayers and their interaction with anti-atrazine
      antibody: building of an immunosensor.
AB  - As a part of our objective to build an immunosensor for the detection of the
      pesticide atrazine (ATZ) in environmental samples, we studied the self-assembling
      process of the disulfide derivative of the pesticide atrazine on a gold
      substrate. Atrazine-based self-assembled monolayers were characterized by
      ellipsometry, scanning tunneling microscopy, polarization-modulation infrared
      reflection-absorption spectroscopy (PM IRRAS), X-ray photoelectron spectroscopy
      and quartz crystal microbalance (QCM) measurements. Two different time constants
      for the adsorption process were observed, depending on the experimental method
      used. The QCM data reflect adsorption kinetics of the original disulfide
      compound, whereas ellipsometry and ex situ PM IRRAS refer to the formation of
      thiolate (ATZS) monolayers. In situ QCM data demonstrated the suitability of such
      monolayers for the detection of atrazine in aqueous samples. Exposure of the ATZS
      sensing surface to an anti-atrazine antibody (anti-ATZ IgG) resulted in complete
      coverage of the surface by antibody, whereas approximately half of the antibody
      molecules were displaced from the QCM sensor surface by further addition of
      atrazine into the solution. 

PMID- 24313271
TI  - Magnetic immunoaffinity enrichment for selective capture and MS/MS analysis of N
      terminal-TMPP-labeled peptides.
AB  - Proteogenomics is the alliance of proteomics and genomics with the aim of better
      annotating structural genes based on experimental, protein-based data items
      established by tandem mass spectrometry. While, on average, more than one-tenth
      of protein N-termini are incorrectly annotated, there is a crucial need for
      methodological approaches to systematically establish the translational starts of
      polypeptides, and their maturations, such as N-terminal methionine processing and
      peptide signal excision. Refinement of genome annotation through correction of
      wrongly annotation initiation start site and detection of unannotated genes can
      be achieved after enrichment and detection of protein N-termini by mass
      spectrometry. Here we describe a straightforward strategy to specifically label
      protein N-termini with a positively charged TMPP label to selectively capture
      these entities with in-house-developed anti-TMPP antibodies coupled to magnetic
      beads and to analyze them by nanoLC-MS/MS. While most N-terminomics-oriented
      approaches are based on the depletion of internal peptides to retrieve N-terminal
      peptides, this enrichment approach is fast and the results are highly specific
      for improved, ionizable, TMPP-labeled peptides. The whole proteome of the model
      marine bacterium, Roseobacter denitrificans, was analyzed, leading to the
      identification of more than twice the number of N-terminal peptides compared with
      the nonenriched fraction. A total of 269 proteins were characterized in terms of
      their N-termini. In addition, three unannotated genes were identified based on
      multiple, redundant N-terminal peptides. Our strategy greatly simplifies the
      systematic and automatic proteogenomic annotation of genomes as well as
      degradomics-oriented approaches, focusing the mass spectrometric efforts on the
      most crucial enriched fractions. 

PMID- 24313272
TI  - Regioselectivity in the nucleophile trapping of arynes: the electronic and steric
      effects of nucleophiles and substituents.
AB  - The regioselectivity in nucleophile trapping is investigated with arynes
      generated directly from bis-1,3-diynes. The regioselectivity is profoundly
      influenced by not only the nature of nucleophiles but also the substituents on
      the arynes, which is the consequence of both the unfavorable steric interaction
      between the incoming nucleophile and the nearby substituent and the inherent
      electronic bias induced by different substituents on the arynes. 

PMID- 24313268
TI  - Oligosaccharide analysis by mass spectrometry: a review of recent developments.

PMID- 24313273
TI  - Graft copolymer nanoparticles with pH and reduction dual-induced disassemblable
      property for enhanced intracellular curcumin release.
AB  - Nanoparticle (NP)-assisted drug delivery systems with disassemblable behaviors in
      response to intracellular microenvironment are urgently demanded in systemic
      cancer chemotherapy for enhanced intracellular drug release. Curcumin (CUR), an
      effective and safe anticancer agent, was limited by its water insolubility and
      poor bioavailability. Herein, pH and reduction dual-induced disassemblable NPs
      for high loading efficiency and improved intracellular release of CUR were
      developed based on an acid degradable cyclic benzylidene acetal groups (CBAs)
      functionalized poly(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl)ethane
      methacrylate)-g-SS-poly(ethylene glycol) (PTTMA-g-SS-PEG) graft copolymer, which
      was readily prepared via RAFT copolymerization and coupling reaction. The NPs
      self-assembled from PTTMA-g-SS-PEG copolymers were stable at physiological pH,
      and quickly disassembled in mildly acidic and reductive environments because of
      the hydrolysis of CBAs in hydrophobic PTTMA core and the cleavage of disulfide
      linked detachable PEG shell. PTTMA-g-SS-PEG NPs exhibited excellent CUR loading
      capacity with drug loading content up to 19.2% and entrapment efficiency of
      96.0%. Within 20 h in vitro, less than 15.0% of CUR was released from the CUR
      loaded NPs in normal physiological conditions, whereas 94.3% was released in the
      presence of reductive agent and mildly acidic conditions analogous to the
      microenvironment in endosome/lysosome and cytoplasm. Confocal fluorescence
      microscopies revealed that the CUR-loaded PTTMA-g-SS-PEG NPs exhibited more
      efficiently intracellular CUR release for EC-109 cells than that of CUR-loaded
      reduction-unresponsive PTTMA-g-PEG NPs and free CUR. In vitro cytotoxicity
      studies displayed blank PTTMA-g-SS-PEG NPs showed low toxicity at concentrations
      up to 1.0 mg/mL, whereas CUR-loaded PTTMA-g-SS-PEG NPs demonstrated more
      efficient growth inhibition toward EC-109 and HepG-2 cells than reduction
      unresponsive controls and free CUR. Therefore, the above results indicated that
      pH and reduction dual-induced disassemblable PTTMA-g-SS-PEG NPs may have emerged
      as superior nanocarriers for active loading and promoted intracellular drug
      delivery in systemic cancer chemotherapy.

PMID- 24313274
TI  - Evidence of entropy-driven bistability through (15)N NMR analysis of a
      temperature- and solvent-induced, chiroptical switching polycarbodiimide.
AB  - The thermo- and solvo-driven chiroptical switching process observed in specific
      polycarbodiimides occurs in a concerted fashion with large deviations in specific
      optical rotation (OR) and CD Cotton effect as a consequence of varying
      populations of two distinct polymer conformations. These two conformations are
      clearly visible in the (15)N NMR and IR spectra of the (15)N-labeled poly((15)N
      (1-naphthyl)-N'-octadecylcarbodiimide) (Poly-3) and poly((15)N-(1-naphthyl)
      (15)N'-octadecylcarbodiimide) (Poly-5). Using van't Hoff analysis, the enthalpies
      and entropies of switching (DeltaHswitching; DeltaSswitching) were calculated for
      both Poly-3 and Poly-5 using the relative integrations of both peaks in the (15)N
      NMR spectra at different temperatures to measure the populations of each state.
      The chiroptical switching (i.e., transitioning from state A to state B) was found
      to be an endothermic process (positive DeltaHswitching) for both Poly-3 and Poly
      5 in all solvents studied, meaning the conformation correlating with the
      downfield chemical shift (ca. 148 ppm, state B) is the higher enthalpy state. The
      compensating factor behind this phenomenon has been determined to be the large
      increase in entropy in CHCl3 as a result of the switching. Herein, we propose
      that the increased entropy in the system is a direct consequence of increased
      disorder in the solvent as the switching occurs. Specifically, the chloroform
      solvent molecules are very ordered around the polymer chains due to favorable
      solvent-polymer interactions, but as the switching occurs, these interactions
      become less favorable and disorder results. The same level of solvent disorder is
      not achieved in toluene, causing the chiroptical switching process to occur at
      higher temperatures. 

PMID- 24313276
TI  - Electrospray ionization (ESI) fragmentations and dimethyldioxirane reactivities
      of three diverse lactams having full, half, and zero resonance energies.
AB  - Three lactams having, respectively, ~20, ~10, and 0 kcal/mol of resonance energy
      have been subjected to electrospray ionization mass spectrometry (ESI/MS) as well
      as to attempted reaction with dimethyldioxirane (DMDO). The ESI/MS for all three
      lactams are consistent with fragmentation from the N-protonated, rather than the
      O-protonated tautomer. Each exhibits a unique fragmentation pathway. DFT
      calculations are employed to provide insights concerning these pathways. N-Ethyl
      2-pyrrolidinone and 1-azabicyclo[3.3.1]nonan-2-one, the full- and half-resonance
      lactams, are unreactive with DMDO. The "Kirby lactam" (3,5,7-trimethyl-1
      azaadamantan-2-one) has zero resonance energy and reacts rapidly with DMDO to
      generate a mixture of reaction products. The structure assigned to one of these
      is the 2,2-dihydroxy-N-oxide, thought to be stabilized by intramolecular hydrogen
      bonding and buttressing by the methyl substituents. A reasonable pathway to this
      derivative might involve formation of an extremely labile N-oxide, in a purely
      formal sense, an example of the hitherto-unknown amide N-oxides, followed by
      hydration with traces of moisture.

PMID- 24313278
TI  - Mechanical resistance of screwless morse taper and screw-retained implant
      abutment connections.
AB  - OBJECTIVE: The screwless morse taper (SMT) implant-abutment connection is an
      alternative to conventional external or internal screw-retained (ISR)
      connections. The aim of this in vitro study was to evaluate mechanical resistance
      of the SMT connection and to compare it with three different ISR connections.
      MATERIALS AND METHODS: Four implant systems were tested in this study: SMT
      system; Tasarimmed Octo (Istanbul, Turkey), ISR systems; Straumann Bone Level
      (Basel, Switzerland), Biohorizons Internal (Birmingham, AL, USA), and Dentsply
      Friadent Xive (Mannheim, Germany). Overall, 64 specimens with stylized single
      crowns were prepared: 32 for dynamic loading (DL) and 32 for static loading (SL).
      DL was carried out using a chewing simulator with 120 N at 1.75 Hz for 1.2 *
      10(6) cycles, and SL was performed with a universal testing machine at a
      crosshead speed of 2 mm/min with an angulation of 30 degrees . Cycles until
      failure from DL and fracture/bending loads at SL were recorded. Statistical
      analyses were made with Dunn's multiple comparison. RESULTS: Median cycles until
      failure in DL were as follows: Octo 86,354 (24,810-153,875), Straumann 1,200,000
      (1,156,618-1,200,000), Biohorizons 539,719 (437,224-858,732), Xive 139,411
      (139,411-139,411). Median fracture/bending loads in Newton at SL were as follows:
      Octo 429.6 (404.5-482.7), Straumann 574.6 (544.6-629.9), Biohorizons 548.7 (532.9
      567.3), Xive 431.5 (412.5-520.5). There were significant differences between the
      implant systems under both loading conditions (P <= 0.05) revealing that the Octo
      implant system's SMT connection showed significantly lower cycles to failures and
      lower fracture/bending loads compared with the ISR connections of the Straumann
      and Biohorizons implant systems. However, there was no significant difference
      compared with the Xive implant system. CONCLUSION: The mechanical resistance of
      the screwless morse taper implant system is lower than that of the ISR implant
      systems that might result in more frequent clinical complications.

PMID- 24313277
TI  - Isomer-specific consumption of galactooligosaccharides by bifidobacterial
      species.
AB  - Prebiotics are nondigestible substrates that stimulate the growth of beneficial
      microbes in the human intestine. Galactooligosaccharides (GOS) are food
      ingredients that possess prebiotic properties, in particular, promoting the
      growth of bifidobacteria in situ. However, precise mechanistic details of GOS
      consumption by bifidobacteria remain poorly understood. Because GOS are mixtures
      of polymers of different lengths and linkages, there is interest in determining
      which specific structures provide prebiotic effects to potentially create better
      supplements. This paper presents a method comprising porous graphitic carbon
      separation, isotopic labeling, and mass spectrometry analysis for the structure
      specific analysis of GOS isomers and their bacterial consumption rate. Using this
      strategy, the differential bacterial consumption of GOS by the bifidobacteria
      species Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp.
      lactis, and Bifidobacterium adolescentis was determined, indicating that the use
      of specific GOS isomers in infant formula may provide enrichment of distinct
      species. 

PMID- 24313279
TI  - Designer psychostimulants in urine by liquid chromatography-tandem mass
      spectrometry.
AB  - Designer psychostimulants are known by recreational drug users to produce a
      complex array of adrenergic and hallucinogenic effects. Many of these drugs are
      not targeted during routine toxicology testing and as a consequence, they are
      rarely reported. The purpose of this study was to develop a procedure for the
      detection of 15 psychostimulants in urine using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS), specifically 2,5-dimethoxy-4-bromophenethylamine (2C-B),
      2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,5-dimethoxy-4-methylphenethylamine
      (2C-D), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxyphenethylamine
      (2C-H), 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4
      ethylthiophenethylamine (2C-T-2), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C
      T-4), 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4
      bromoamphetamine (DOB), 2,5-dimethoxy-4-chloroamphetamine (DOC), 2,5-dimethoxy-4
      ethylamphetamine (DOET), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5-dimethoxy-4
      methylamphetamine (DOM), and 4-methylthioamphetamine (4-MTA). Analytical
      recoveries using solid-phase extraction were 64-92% and the limit of detection
      was 0.5 ng/mL for all drugs except 2C-B (1 ng/mL). The assay was evaluated in
      terms of analytical recovery, precision, accuracy, linearity, matrix effect, and
      interferences. The technique allows for the simultaneous detection of 15
      psychostimulants at sub-ng/mL concentrations.

PMID- 24313280
TI  - Age-related changes in mitochondrial function of mouse colonic smooth muscle:
      beneficial effects of melatonin.
AB  - Aging is a multifactorial process that involves biochemical, structural, and
      functional changes in mitochondria. The ability of melatonin to palliate the
      alterations induced by aging is based on its chronobiologic, antioxidant, and
      mitochondrial effects. There is little information about the effects of melatonin
      on the in situ mitochondrial network of aging cells and its physiological
      implications. We have studied the ability of melatonin to prevent the functional
      alterations of in situ mitochondria of smooth muscle cells and its impact on
      contractility. Mitochondrial membrane potential was recorded in isolated colonic
      smooth muscle cells from young mice (3 month old), aged mice (22-24-month old),
      and aged mice treated with melatonin (starting at 14-month age). Aging induced a
      partial mitochondrial depolarization in resting conditions and reduced the
      depolarizing response to cellular stimulation. Use of oligomycin indicated that
      aging enhanced the resting activity of the mitochondrial ATP synthase, whereas in
      young cells, the enzyme operated mainly in reverse mode. Melatonin treatment
      prevented all these changes. Aging reduced both spontaneous and stimulated
      contraction of colonic strips and shifted the metabolic dependence of contraction
      from mitochondria to glycolysis, as indicated the use of mitochondrial and
      glycolysis inhibitors. These functional alterations were also palliated by
      melatonin treatment. Aging effects were not related to a decrease in Ca2+ store
      mobilization, because this was enhanced in aged cells and restored by melatonin.
      In conclusion, melatonin prevents the age induced in situ mitochondrial potential
      alterations in smooth muscle cells and the associated changes in contractility
      and metabolism.

PMID- 24313281
TI  - Spontaneous progression of cutaneous angiomatosis to an infiltrative sarcoma-like
      tumour in a bull.
AB  - CASE HISTORY: A 5-month-old valuable Red Holstein bull presented with a cutaneous
      mass on the fetlock of the right hind limb. The mass was removed and
      histologically diagnosed as a benign angiomatosis. Four months later, the mass
      reoccurred on the same leg. PATHOLOGICAL FINDINGS: The first excision biopsy
      consisted of numerous blood vessels of different diameters and wall thicknesses.
      Often, the smaller vessels were oriented around a larger, vein-like vessel. The
      endothelial cells were elongated with small oval to elongated nuclei with dense
      chromatin. Following recurrence, the mass showed clear signs of infiltrative
      growth, including solid bundles of cells, increased polymorphism and round to
      oval nuclei with coarse chromatin and distinctive nucleoli. The neoplastic cells
      were immunohistochemically positive for von Willebrand Factor (vWF). DIAGNOSIS:
      Angiomatosis with focal progression to an infiltrative growing sarcoma-like
      tumour. CLINICAL RELEVANCE: This case represents the progression of a benign
      vascular proliferation, often considered as a reactive process, into a more
      aggressively behaving neoplasm. The clinical behaviour and histopathological
      morphology were strikingly similar to previous cases described in human and
      veterinary medicine.

PMID- 24313282
TI  - Core-shell nanocarriers for cancer therapy. Part I: biologically oriented design
      rules.
AB  - INTRODUCTION: The application of nanotechnologies to the cancer field for
      therapeutic, imaging or diagnostic purposes represents an advanced and very
      attractive approach to overcome the main limits related to conventional
      chemotherapy. In particular, core-shell nanocarriers can be engineered to provide
      adequate features to overcome the main biological barriers encountered by free
      anti-cancer drugs. AREAS COVERED: This review will try to summarise the design
      rules - as dictated by biological requirements - to take into account for proper
      nanocarrier design and to highlight the potential of administration routes other
      than intravenous. EXPERT OPINION: Although intravenous injection remains the most
      investigated route of administration for 'nanoncologicals', research interest
      towards less explored administration routes allowing localised chemotherapy or
      delivery in close proximity to the tumour site might change the way cancer is
      treated in the near future. Nevertheless, an experimental set-up more
      biologically oriented taking into account an in-depth evaluation of stability in
      complex media, protein interaction, and cell interaction of novel nanoconstructs
      could allow their successful translation in pre-clinical and clinical settings.

PMID- 24313283
TI  - Identification of patients at risk of contaminated blood culture.

PMID- 24313284
TI  - Non-quinolone inhibitors of bacterial type IIA topoisomerases: a feat of
      bioisosterism.

PMID- 24313285
TI  - Window to the wandering mind: pupillometry of spontaneous thought while reading.
AB  - Mind-wandering is both pervasive and detrimental to task performance. As such,
      identifying covert physiological measures that are associated with this off-task
      state could inform theories of mind-wandering and lead to interventions that
      improve task focus. Although previous work suggests that pupil dilation (PD) may
      vary between on- and off-task states, no studies have examined whether PD
      systematically varies within a subject as they report becoming disengaged from a
      task-a key step in developing useful mind-wandering prediction algorithms. In the
      present study, PD was measured while participants advanced through a passage one
      word at a time. Spontaneous mind-wandering was assessed during reading using
      standard thought probe methodology. Results revealed higher PD prior to off-task
      than prior to on-task reading. This newly discovered relationship between
      momentary fluctuations of attention and PD offers promise for future innovations
      that use these systematic changes in PD to predict and better control mind
      wandering. 

PMID- 24313286
TI  - Hodgkin lymphoma patients in first remission: routine positron emission
      tomography/computerized tomography imaging is not superior to clinical follow-up
      for patients with no residual mass.
AB  - There is no consensus regarding optimal follow-up mode for Hodgkin lymphoma (HL)
      patients that achieve complete remission following chemotherapy or combined chemo
      and radiation therapy. Several studies demonstrated high sensitivity of positron
      emission tomography/computerized tomography (PET/CT) in detecting disease
      progression; however, these techniques are currently not recommended for routine
      follow-up. This retrospective study conducted in two Israeli (N = 291) and one
      New Zealand academic centres (N = 77), compared a group of HL patients, followed
      up with routine imaging every 6 months during the first 2 years after achieving
      remission, once in the third year, with additional dedicated studies performed
      due to symptoms or physical findings (Group I) to a group of patients without
      residual masses who underwent clinically-based surveillance with dedicated
      imaging upon relapse suspicion (Group II). Five-year overall survival (OS) was
      94% and median time to relapse was 8.6 months for both modes. Relapse rates in
      Groups I and II were 13% and 9%, respectively. During the first 3 years of follow
      up, 47.5 and 4.7 studies were performed per detected relapse in Groups I and II,
      respectively. The current study demonstrated no benefit in either progression
      free survival (PFS) or OS in HL patients followed by routine imaging versus
      clinical follow-up. The cost was 10 times higher for routine imaging. 

PMID- 24313288
TI  - Response: Old-to-old pancreas transplantation, what's old in the USA may be young
      in Europe.

PMID- 24313287
TI  - Ethanol, not detectably metabolized in brain, significantly reduces brain
      metabolism, probably via action at specific GABA(A) receptors and has measureable
      metabolic effects at very low concentrations.
AB  - Ethanol is a known neuromodulatory agent with reported actions at a range of
      neurotransmitter receptors. Here, we measured the effect of alcohol on metabolism
      of [3-13C]pyruvate in the adult Guinea pig brain cortical tissue slice and
      compared the outcomes to those from a library of ligands active in the GABAergic
      system as well as studying the metabolic fate of [1,2-13C]ethanol. Analyses of
      metabolic profile clusters suggest that the significant reductions in metabolism
      induced by ethanol (10, 30 and 60 mM) are via action at neurotransmitter
      receptors, particularly alpha4beta3delta receptors, whereas very low
      concentrations of ethanol may produce metabolic responses owing to release of
      GABA via GABA transporter 1 (GAT1) and the subsequent interaction of this GABA
      with local alpha5- or alpha1-containing GABA(A)R. There was no measureable
      metabolism of [1,2-13C]ethanol with no significant incorporation of 13C from [1,2
      13C]ethanol into any measured metabolite above natural abundance, although there
      were measurable effects on total metabolite sizes similar to those seen with
      unlabelled ethanol.

PMID- 24313289
TI  - Association of cytokine gene polymorphisms in patients with tuberculosis and
      their household contacts.
AB  - Cytokine gene polymorphisms are known to be associated with functional
      differences in cytokine regulation and may affect host susceptibility to
      tuberculosis (TB). Contacts are important group in developing tuberculosis
      infection and are 10-60 times more likely to develop TB than general population.
      The present study was carried out in patients with TB (N = 176), their household
      contacts (HHC; N = 155) from Free Chest TB Clinic PPM DOTS (1TU) covering 500,000
      population at Mahavir Hospital and Research Centre, Hyderabad, and healthy
      controls (HC; N = 170) also included. The association of single-nucleotide
      polymorphisms (SNPs) in the promoter region of TNF-alpha (-308G/A), IL-2 (
      330T/G), IL-4 (-589C/T) and in exon region of TGF-beta1 (+869T/C) genes was
      assessed by ARMS & PCR-RFLP using specific primers in the above-mentioned
      subjects. The differences in allelic or genotypic frequencies of TNF-alpha (
      308G/A) between patients, their HHC and HC were not statistically significant (P
      > 0.05). IL-2 (-330T/G) TG genotype was significantly different between patients,
      HHC compared to HC (P < 0.002, OR-1.997, 95%CI-1.260-3.168, P < 0.03, OR-1.602,
      955CI-1.003-2.561).IL-4 (-589C/T) CC genotype was significantly different between
      patients and HC (P < 0.03, OR-1.791, 95%CI-1.009-3.189) as well as between HHC
      and HC at P < 0.0001, OR-2.56, 95%CI-1.448-4.545. In addition, the TGF-beta 1
      (+869T/C) TC genotype was significantly associated with susceptibility to
      tuberculosis in patients when compared against HC(P < 0.0001, OR-3.416, 95%CI
      2.063-5.670) and HHC (P < 0.0001, OR-2.357, 95%CI-1.439-3.868), respectively.MDR
      analysis indicated that TT genotype of TGF-beta1 with TT and CT genotypes of IL-4
      showed high risk with GA, TT genotypes of TNF-alpha, IL-2, respectively. Our
      results suggest that IL-2 (-330T/G), IL-4 (-589 C/T) and TGF-beta1 (+869T/C) gene
      polymorphisms may be associated with TB susceptibility. 

PMID- 24313292
TI  - Efficient inorganic-organic hybrid perovskite solar cells based on pyrene
      arylamine derivatives as hole-transporting materials.
AB  - A set of three N,N-di-p-methoxyphenylamine-substituted pyrene derivatives have
      successfully been synthesized and characterized by (1)H/(13)C NMR spectroscopy,
      mass spectrometry, and elemental analysis. The optical and electronic structures
      of the pyrene derivatives were adjusted by controlling the ratio of N,N-di-p
      methoxyphenylamine to pyrene, and investigated by UV/vis spectroscopy and cyclic
      voltammetry. The pyrene derivatives were employed as hole-transporting materials
      (HTMs) in fabricating mesoporous TiO2/CH3NH3PbI3/HTMs/Au solar cells. The pyrene
      based derivative Py-C exhibited a short-circuit current density of 20.2 mA/cm(2),
      an open-circuit voltage (Voc) of 0.886 V, and a fill factor of 69.4% under an
      illumination of 1 sun (100 mW/cm(2)), resulting in an overall power conversion
      efficiency of 12.4%. The performance is comparable to that of the well-studied
      spiro-OMeTAD, even though the Voc is slightly lower. Thus, this newly synthesized
      pyrene derivative holds promise as a HTM for highly efficient perovskite-based
      solar cells. 

PMID- 24313291
TI  - Blockage of the upregulation of voltage-gated sodium channel nav1.3 improves
      outcomes after experimental traumatic brain injury.
AB  - Excessive active voltage-gated sodium channels are responsible for the cellular
      abnormalities associated with secondary brain injury following traumatic brain
      injury (TBI). We previously presented evidence that significant upregulation of
      Nav1.3 expression occurs in the rat cortex at 2 h and 12 h post-TBI and is
      correlated with TBI severity. In our current study, we tested the hypothesis that
      blocking upregulation of Nav1.3 expression in vivo in the acute stage post-TBI
      attenuates the secondary brain injury associated with TBI. We administered either
      antisense oligodeoxynucleotides (ODN) targeting Nav1.3 or artificial
      cerebrospinal fluid (aCSF) at 2 h, 4 h, 6 h, and 8 h following TBI. Control sham
      animals received aCSF administration at the same time points. At 12 h post-TBI,
      Nav1.3 messenger ribonucleic acid (mRNA) levels in bilateral hippocampi of the
      aCSF group were significantly elevated, compared with the sham and ODN groups
      (p<0.01). However, the Nav1.3 mRNA levels in the uninjured contralateral
      hippocampus of the ODN group were significantly lowered, compared with the sham
      group (p<0.01). Treatment with antisense ODN significantly decreased the number
      of degenerating neurons in the ipsilateral hippocampal CA3 and hilar region
      (p<0.01). A set of left-to-right ratio value analyzed by magnetic resonance
      imaging T2 image on one day, three days, and seven days post-TBI showed marked
      edema in the ipsilateral hemisphere of the aCSF group, compared with that of the
      ODN group (p<0.05). The Morris water maze memory retention test showed that both
      the aCSF and ODN groups took longer to find a hidden platform, compared with the
      sham group (p<0.01). However, latency in the aCSF group was significantly higher
      than in the ODN group (p<0.05). Our in vivo Nav1.3 inhibition studies suggest
      that therapeutic strategies to block upregulation of Nav1.3 expression in the
      brain may improve outcomes following TBI.

PMID- 24313290
TI  - Regulation of with-no-lysine kinase signaling by Kelch-like proteins.
AB  - In 2001, with-no-lysine (WNK) kinases were identified as the genes responsible
      for the human hereditary hypertensive disease pseudohypoaldosteronism type II
      (PHAII). It took a further 6 years to clarify that WNK kinases participate in a
      signaling cascade with oxidative stress-responsive gene 1 (OSR1), Ste20-related
      proline-alanine-rich kinase (SPAK), and thiazide-sensitive NaCl cotransporter
      (NCC) in the kidney and the constitutive activation of this signaling cascade is
      the molecular basis of PHAII. Since this discovery, the WNK-OSR1/SPAK-NCC
      signaling cascade has been shown to be involved not only in PHAII but also in the
      regulation of blood pressure under normal and pathogenic conditions, such as
      hyperinsulinemia. However, the molecular mechanisms of WNK kinase regulation by
      dietary and hormonal factors and by PHAII-causing mutations remain poorly
      understood. In 2012, two additional genes responsible for PHAII, Kelch-like 3
      (KLHL3) and Cullin3, were identified. At the time of their discovery, the
      molecular mechanisms underlying the interaction between these genes and their
      involvement in PHAII were unknown. Here we review the pathophysiological roles of
      the WNK signaling cascade clarified to date and introduce a new mechanism of WNK
      kinase regulation by KLHL3 and Cullin3, which provides insight on previously
      unknown mechanisms of WNK kinase regulation. 

PMID- 24313293
TI  - The morphology of three Loxophyllum species (Ciliophora, Pleurostomatida) from
      southern China, L. lembum sp. n., L. vesiculosum sp. n. and L. perihoplophorum
      Buddenbrock, 1920, with notes on the molecular phylogeny of Loxophyllum.
AB  - Two new pleurostomatid ciliates, Loxophyllum lembum sp. n., L. vesiculosum sp.
      n., and the poorly known L. perihoplophorum Buddenbrock, 1920, isolated from
      brackish waters in coastal regions of southern China, are described following
      observations of live cells and protargol-impregnated specimens. Loxophyllum
      lembum sp. n. is distinguished by a combination of characters including two
      macronuclear nodules, 6-9 contractile vacuoles along the ventral margin, 11-14
      right and 6-8 left kineties and the presence of cortical granules. Loxophyllum
      vesiculosum sp. n. differs from its congeners mainly by the unique distribution
      of contractile vacuoles, several of which lie along the dorsal margin and one on
      the ventral margin, and 15-21 right and 6-8 left kineties. Loxophyllum
      perihoplophorum is characterized by its large cell size (350-450 MUm long in
      vivo), 3-5 contractile vacuoles along the dorsal margin in the posterior region
      of the body, and 19-23 right and 7-9 left kineties. An improved diagnosis of L.
      perihoplophorum is provided. The SSU rDNA sequence of L. perihoplophorum is
      reported for the first time and its molecular phylogeny is analyzed. Maximum
      likelihood and Bayesian inference analyses of SSU rDNA sequence data recover the
      monophyly both of the order Pleurostomatida and of the genus Loxophyllum.

PMID- 24313294
TI  - Transgender women and the sex work industry: roots in systemic, institutional,
      and interpersonal discrimination.
AB  - Because transgender people face discrimination on systemic, institutional, and
      interpersonal levels, the previous literature has supported that many transgender
      women view the sex work industry as their only viable career option. The current
      article reviews the literature on discrimination against transgender people,
      explores how discrimination influences their participation in sex work, and
      discusses how institutional discrimination against transgender women manifests
      within the criminal justice system. Furthermore, recommendations are provided for
      advocating for the rights of transgender people while promoting healthy behaviors
      and higher quality of life. Throughout the article, quotes from previous
      qualitative research are used to illustrate the experiences of transgender women
      through their own voices and perspectives. 

PMID- 24313295
TI  - Recurrent splice-site mutation in MBTPS2 underlying IFAP syndrome with Olmsted
      syndrome-like features in a Chinese patient.
AB  - Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum of X
      linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and
      photophobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies,
      retardation of mentality and growth, ectodermal dysplasia, skeletal
      malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia,
      cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia) syndrome,
      keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) and an X-linked
      form of Olmsted syndrome. We report a recurrent intronic mutation in MBTPS2
      (c.671-9T>G) in a Chinese patient with the typical triad of IFAP syndrome (i.e.
      ichthyosis, atrichia and photophobia), along with pachyonychia, palmoplantar and
      periorificial keratoderma, which were reminiscent of Olmsted syndrome.
      Interestingly, this mutation was previously reported in two cases of IFAP without
      keratoderma, which suggests clinical heterogeneicity of the same mutation in
      MBTPS2. The concomitance of Olmsted syndrome-like features in this patient with
      IFAP may challenge the existence of the X-linked form of Olmsted syndrome as an
      independent condition.

PMID- 24313296
TI  - Investigating the influence of the interface in thiol-functionalized silver-gold
      nanoshells over lipase activity.
AB  - We employed thiol-funcionalized AgAu nanoshells (AgAu NSs) as supports for the
      covalent attachment of lipases (BCL, Burkholderia cepacia lipase; PPL, pancreatic
      porcine lipase). Specifically, we were interested in investigating the effect of
      the nature/size of the spacer in AgAu NSs-functionalized organic thiols over the
      covalent attachment of lipases. The catalytic performance of AgAu-lipase systems
      was measured in the kinetic resolution of (R,S)-1-(phenyl)ethanol via a
      transesterification reaction. In comparison to free BCL, the lipase attached to
      AgAu NSs using a small spacer such as cysteamine or mercaptoacetic acid, with the
      largest spacer mercaptoundecanoic acid, had the fastest conversion rate. The
      recycling potential for BCL was investigated. After three reaction cycles, the
      enzyme activity was kept at around 90% of the initial value. The results
      described herein show that the size of the spacer plays an important role in
      optimizing lipase activities in metallic nanoshells as solid supports. 

PMID- 24313297
TI  - Bombing alone: tracing the motivations and antecedent behaviors of lone-actor
      terrorists,.
AB  - This article analyzes the sociodemographic network characteristics and antecedent
      behaviors of 119 lone-actor terrorists. This marks a departure from existing
      analyses by largely focusing upon behavioral aspects of each offender. This
      article also examines whether lone-actor terrorists differ based on their
      ideologies or network connectivity. The analysis leads to seven conclusions.
      There was no uniform profile identified. In the time leading up to most lone
      actor terrorist events, other people generally knew about the offender's
      grievance, extremist ideology, views, and/or intent to engage in violence. A wide
      range of activities and experiences preceded lone actors' plots or events. Many
      but not all lone-actor terrorists were socially isolated. Lone-actor terrorists
      regularly engaged in a detectable and observable range of activities with a wider
      pressure group, social movement, or terrorist organization. Lone-actor terrorist
      events were rarely sudden and impulsive. There were distinguishable behavioral
      differences between subgroups. The implications for policy conclude this article.

PMID- 24313298
TI  - Flavonoids from Podocarpus macrophyllus and their cardioprotective activities.
AB  - One new 8-aryl flavone, podocarflavone A (1), together with 15 previously
      reported flavonoids were isolated from the twigs and leaves of Podocarpus
      macrophyllus. Their structures were established on the basis of extensive
      spectroscopic analysis and by the comparison with spectroscopic data reported in
      the literature. Antioxidant capacities of the isolated substances were determined
      using the 1,1-diphenyl-2-picrylhydrazyl, ferrous ions, and 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid) radical in vitro assays, and their
      cytoprotective activities were also tested on H2O2-induced apoptosis in H9c2
      cardiomyocytes. The results showed that those flavonoids exhibited significant
      cardioprotective effects by decreasing the H2O2-induced death of H9c2 cell, and
      the levels of lactate dehydrogenase and creatine kinase, and by inhibiting the
      elevated intracellular concentration of reactive oxygen species. 

PMID- 24313299
TI  - New triterpenoids and other constituents from the fruits of Benincasa hispida
      (Thunb.) Cogn.
AB  - Benincasa hispida (Thunb.) Cogn. fruits are widely consumed in China and tropical
      countries. This study identifies three new triterpenoids, 3alpha,29-O-di-trans
      cinnamoyl-D:C-friedooleana-7,9(11)-diene (1), oleanolic acid 28-O-beta-d
      xylopyranosyl-[beta-d-xylopyranosyl-(1->4)]-(1->3)-alpha-l-rhamnopyranosyl-(1->2)
      alpha-l-arabinopyranoside (2), and oleanolic acid 28-O-beta-d-glucopyranosyl-(1
      >3)-beta-d-xylopyranosyl-[beta-d-xylopyranosyl-(1->4)]-(1->3)-alpha-l
      rhamnopyranosyl-(1->2)-alpha-l-arabinopyranoside (3), together with 12 known
      compounds, multiflorenol (4), isomultiflorenyl acetate (5), stigmasterol (6),
      stigmasterol 3-O-beta-d-glucopyranoside (7), alpha-spinasterol (8), alpha
      spinasterol 3-O-beta-d-glucopyranoside (9), beta-sitosterol (10), daucosterol
      (11), arbutin (12), nicotinic acid (13), (+)-pinonesinol (14), and ethyl beta-d
      glucopyranoside (15). The structures of compounds 1-15 were determined by
      spectroscopic and chemical methods. All the compounds with the exception of 4, 5,
      and 9-11 were isolated from B. hispida for the first time. The anticomplement
      activities of compounds 1-15 were assessed by Mayer's modified method. Compounds
      1-15 showed no significant cytotoxic activity against HeLa human cervical, HL-60
      human hepatoma, and SMMC-7721 human hepatoma cell lines. 

PMID- 24313300
TI  - The experience of group mindfulness-based interventions for individuals with
      mental health difficulties: a meta-synthesis.
AB  - OBJECTIVE: The aim of this paper was to synthesize the findings of qualitative
      studies examining the experience of individuals with mental health difficulties
      attending mindfulness-based interventions. METHOD: A meta-synthesis of 15
      qualitative studies was carried out, using a thematic synthesis approach.
      RESULTS: The meta-synthesis identified eight analytical themes: 'prior
      experiences and expectations', 'normalising and supportive process of the group',
      'relating differently to thoughts and feelings', 'acceptance', 'a sense of
      control and choice', 'relationship with self and others', 'struggles', and
      'awareness'. CONCLUSIONS: A conceptual framework is presented which accounts for
      the participants' experiences and suggests a process through which they
      renegotiate their relationship with their mental health difficulties.

PMID- 24313301
TI  - MSiMass list: a public database of identifications for protein MALDI MS imaging.
AB  - The clinical application of mass spectrometry imaging has developed into a
      sizable subdiscipline of proteomics and metabolomics because its seamless
      integration with pathology enables biomarkers and biomarker profiles to be
      determined that can aid patient and disease stratification (diagnosis, prognosis,
      and response to therapy). Confident identification of the discriminating peaks
      remains a challenge owing to the presence of nontryptic protein fragments, large
      mass-to-charge ratio ions that are not efficiently fragmented via tandem mass
      spectrometry or a high density of isobaric species. A public database of
      identifications has been initiated to aid the clinical development and
      implementation of mass spectrometry imaging. The MSiMass list database (
      www.maldi-msi.org/mass ) enables users to assign identities to the peaks observed
      in their experiments and provides the methods by which the identifications were
      obtained. In contrast with existing protein databases, this list is designed as a
      community effort without a formal review panel. In this concept, authors can
      freely enter data and can comment on existing entries. In such, the database
      itself is an experiment on sharing knowledge, and its ability to rapidly provide
      quality data will be evaluated in the future. 

PMID- 24313302
TI  - Meaningful and enjoyable or boring and depressing? The reasons student nurses
      give for and against a career in aged care.

PMID- 24313303
TI  - Influence of immediate loading on healing of implants installed with different
      insertion torques--an experimental study in dogs.
AB  - OBJECTIVE: To evaluate the influence of different insertion torques on healing of
      implants loaded immediately or left unloaded. MATERIAL AND METHODS: In six
      Labrador dogs, all mandibular premolars and molars were extracted. After 4 months
      of healing, flaps were elevated, and two implant sites were prepared at each side
      of the mandible. The distal sites were prepared conventionally while the mesial
      sites were underprepared by 0.3 mm. As a consequence, different final insertion
      torques of about 30 Ncm at the distal and >70 Ncm at the mesial sites were
      recorded. Healing abutments were applied to the left and transmucosal abutments
      to the right side. Flaps were sutured, crown preparation of the upper right
      second and third premolars was performed, and impressions were taken. Within 24
      h, crowns were cemented both to implants and teeth in the right side of the
      mouth. After 4 months, the animals were sacrificed and ground sections obtained
      for histological evaluation. RESULTS: A higher buccal bony crestal resorption and
      a more apical position of the coronal level of osseointegration were found at the
      loaded compared with the unloaded sites. MBIC% and percentages of peri-implant
      mineralized tissue (MB%) were higher at the loaded compared with the unloaded
      sites. Moreover, a higher MBIC% was found at the lower compared with the higher
      final insertion torque. CONCLUSIONS: Immediate loading does not seem to have a
      negative effect on osseointegration. High torque values for the immediate loading
      procedures were not necessary. Probably, low torque values, were sufficient to
      obtain primary stability and hence may provide better osseointegration than high
      torque value.

PMID- 24313304
TI  - Gas-phase ion isomer analysis reveals the mechanism of peptide sequence
      scrambling.
AB  - Peptide sequence scrambling during mass spectrometry-based gas-phase
      fragmentation analysis causes misidentification of peptides and proteins. Thus,
      there is a need to develop an efficient approach to probing the gas-phase
      fragment ion isomers related to sequence scrambling and the underlying
      fragmentation mechanism, which will facilitate the development of bioinformatics
      algorithm for proteomics research. Herein, we report on the first use of electron
      transfer dissociation (ETD)-produced diagnostic fragment ions to probe the
      components of gas-phase peptide fragment ion isomers. In combination with ion
      mobility spectrometry (IMS) and formaldehyde labeling, this novel strategy
      enables qualitative and quantitative analysis of b-type fragment ion isomers. ETD
      fragmentation produced diagnostic fragment ions indicative of the precursor ion
      isomer components, and subsequent IMS analysis of b ion isomers provided their
      quantitative and structural information. The isomer components of three
      representative b ions (b9, b10, and b33 from three different peptides) were
      accurately profiled by this method. IMS analysis of the b9 ion isomers exhibited
      dynamic conversion among these structures. Furthermore, molecular dynamics
      simulation predicted theoretical drift time values, which were in good agreement
      with experimentally measured values. Our results strongly support the mechanism
      of peptide sequence scrambling via b ion cyclization, and provide the first
      experimental evidence to support that the conversion from molecular precursor ion
      to cyclic b ion (M -> (c)b) pathway is less energetically (or kinetically)
      favored. 

PMID- 24313305
TI  - Melatonin treatment combined with treadmill exercise accelerates muscular
      adaptation through early inhibition of CHOP-mediated autophagy in the
      gastrocnemius of rats with intra-articular collagenase-induced knee laxity.
AB  - The purpose of this study was to determine the effects of melatonin intervention
      on gastrocnemius remodeling in rats with collagenase-induced knee instability.
      Type VII collagenase was injected into the right knee to induce joint laxity with
      cartilage destruction. Melatonin (MT; 10 mg/kg) injection was performed twice
      daily subcutaneously, and treadmill exercise (Ex; 11 m/min) was conducted for 1
      hr/day at a frequency of 5 days/wk for 4 wks. The gastrocnemius mass, which was
      reduced with collagenase injection only (Veh), was increased with collagenase
      injection with melatonin treatment with and without exercise in the early phase,
      and the mass in both limbs was significantly different in the Veh compared with
      the MT group. However, there was an increase in the relative muscle weight to
      body weight ratio in the Veh group at the advanced stage. Insulin-like growth
      factor receptor (IGF-IR) was downregulated in the Veh group, whereas IGF-IR was
      upregulated in the MT and MT + Ex groups. Joint laxity induced enhancement of
      autophagic proteolysis (LC3 II) in the muscle, which was recovered to values
      similar to those in the normal control group (Con) compared with those in the MT
      and MT+Ex groups. Although intra-articular collagenase increased the total C/EBP
      homology protein (CHOP) levels at 1 wk and decreased them at 4 wks in the Veh
      group, CHOP in the nucleus was upregulated continuously. Prolonged melatonin
      treatment with and without exercise intervention suppressed nuclear localization
      of ATF4 and CHOP with less activation of caspase-3, at the advanced phase.
      Moreover, the interventions promoted the expression of myosin heavy chain (MHC)
      isoforms under the control of myogenin. Concomitant with a beneficial effect of
      melatonin with and without exercise, step length of the saline-injected limb and
      the collagenase-injected supporting side was maintained at values similar to
      those in control rats. Taken together, the findings demonstrate that melatonin
      with and without exercise accelerate remodeling of the gastrocnemius through
      inhibition of nuclear CHOP in rats with collagenase-induced knee instability.

PMID- 24313306
TI  - Catalysis for the valorization of exhaust carbon: from CO2 to chemicals,
      materials, and fuels. technological use of CO2.

PMID- 24313307
TI  - Rapid bedside coagulometry prior to urgent neurosurgical procedures in
      anticoagulated patients.
AB  - INTRODUCTION: With the increased use of oral anticoagulation with vitamin K
      antagonists, emergency physicians encounter a growing number of patients
      requiring a rapid reversal of anticoagulant effects in order to perform urgent
      surgical procedures. Initiation of these procedures can be delayed because the
      coagulation status has to be assessed through examination of blood samples in
      central laboratories (CL). This delay may lead to negative effects, especially in
      potentially life-threatening conditions such as intracranial haemorrhage. Point
      of-care (POC) devices for assessment of international normalized ratio (POC INR)
      have improved the management of anticoagulation therapy in the outpatient
      setting. The use of these devices may also have beneficial effects in the
      treatment of anticoagulated patients requiring urgent neurosurgical procedures.
      The primary aim of this study was to analyse the potential of POC-guided
      assessment of INR to reduce time to potentially life-saving neurosurgery in this
      setting. Feasibility and accuracy as well as the gain of time through the use of
      this device were analysed. MATERIALS AND METHODS: The POC coagulometer CoaguChek
      XS((r)) was used in 17 patients with a history of anticoagulant use and a
      condition requiring urgent anticoagulant reversal prior to neurosurgical
      procedures (burr-hole trepanation: n = 8, craniotomy: n = 7, laminectomy: n = 2).
      RESULTS: No technical difficulties occurred and rapid assessment of INR was
      achieved in all cases within 2 min. POC INR values correlated well with CL INR
      assessment with a mean INR deviation of 0.036 +/- 0.12. The mean gain of time
      through the use of the POC INR device compared with CL assessment of INR was 47
      +/- 6 min (range: 37-61 min). CONCLUSION: Our initial experiences with a POC INR
      device in anticoagulated patients undergoing urgent neurosurgical procedures
      demonstrate that its use may contribute to an improved management of these
      patients.

PMID- 24313308
TI  - Analysis of the incidence and risk factors for the progression of proximal
      junctional kyphosis following surgical treatment for lumbar degenerative
      kyphosis: minimum 2-year follow-up.
AB  - BACKGROUND CONTEXT. Proximal junctional kyphosis (PJK) following surgical
      treatment of lumbar degenerative kyphosis (LDK) is one of the critical
      complications leading to the failure of instrumentation and additional extensive
      surgery. However, most previous studies have focused on idiopathic scoliosis
      resulting from variable surgical techniques. LDK usually differ from other
      scoliotic deformities in terms of patient characteristics and disease mechanisms.
      PURPOSE. Identification of the prevalence of PJK after the surgical treatment of
      LDK and searching for the predictable value for the progression of PJK. Study
      design. Retrospective comparative study. Patient sample (must be included in
      clinical studies). Forty-seven consecutive patients who underwent surgical
      correction of a sagittal imbalance due to LDK, from January 2005 to December 2008
      in a single spine clinic, were evaluated with a minimum 2 years follow-up (mean
      3.8 years). METHODS. Patients were divided into 2 groups: with or without the
      occurrence of PJK, and three categorized factors according to patient
      characteristics, surgical variables, and the radiographic spinopelvic parameters
      were evaluated. RESULTS. PJK had occurred in 29 of 47 patients (61.7%). Among
      variable factors, old age, upper-instrumented vertebra below L2, lumbar lordosis
      to PI ratio, and the sum of lumbar lordosis, and the sacral slope related to PI
      were found to be statistically significant. CONCLUSIONS. The overall incidence of
      PJK following surgical treatment of LDK patients was higher than expected. Spinal
      biomechanics may be changed after long instrumented fusion surgery. Thorough
      consideration of these factors is needed in the treatment strategy of LDK
      patients. A long-term follow-up study should be conducted.

PMID- 24313309
TI  - Delayed post-operative haemorrhage after carmustine wafer implantation: a case
      series from two UK centres.
AB  - OBJECT: Significant haemorrhage following intracranial tumour resection may occur
      in 1-2% of cases and the majority occur within the first few hours post
      operatively. Implantation of carmustine wafers has been associated with increased
      operative site complications in some series, but post-operative haematoma is not
      routinely reported. We analyzed the characteristics of post-operative haemorrhage
      after carmustine wafer insertion. METHODS: We performed a retrospective audit of
      surgical site haematoma after tumour resection and insertion of carmustine wafers
      in two neurosurgical units in the UK (University Hospital of North Staffordshire,
      Stoke-on-Trent, March 2003 - July 2012; Wessex Neurological Centre, Southampton,
      October 2005 - January 2013). RESULTS: During the specified time periods,
      carmustine wafers were inserted in 181 operations in 177 patients. We identified
      acute operative site haematomas after carmustine wafer insertion in 8 (4.4%)
      patients. All presented in a delayed fashion on or after Day 2 post-operatively.
      In contrast, acute operative site haematoma was present in 4/491 (0.81%) of
      patients who underwent resection without gliadel wafer insertion. CONCLUSIONS: In
      contrast to the expected timing of bleeding following intracranial tumour
      resection, all carmustine wafer patients who experienced haemorrhage presented in
      a delayed fashion on or after Day 2 post-operatively. The causative factors for
      universally delayed post-operative haematoma after carmustine wafer insertion are
      unclear and further studies are required to characterize this phenomenon.

PMID- 24313311
TI  - Design of polypyrrole/polyaniline double-walled nanotube arrays for
      electrochemical energy storage.
AB  - The novel hybrid polypyrrole (PPy)/polyaniline (PANI) double-walled nanotube
      arrays (DNTAs) were designed to exploit the synergistic effects and shape effects
      for supercapacitive energy storage. The PPy/PANI DNTAs showed large specific
      capacitance (Csp) of 693 F/g at a scan rate of 5 mV/s. The PPy/PANI DNTAs also
      exhibited good rate capability and high long-term cycle stability (less 8% loss
      of the maximum specific capacitance after 1000 cycles). The synergistic effects
      between PPy and PANI, the shape effects of nanotube arrays and double-walled
      nanostructures, and high utilization rate of electrode are crucial for the
      outstanding performance of PPy/PANI DNTAs. The large Csp, good rate capability,
      and high long-term cycle stability offered by the PPy/PANI DNTAs, make them
      promising candidate electrodes for high-performance supercapacitors. 

PMID- 24313312
TI  - Synthesis of c-di-GMP analogs with thiourea, urea, carbodiimide, and guanidinium
      linkages.
AB  - The first syntheses of neutral thiourea, urea, and carbodiimide analogs, along
      with two guanidinium analogs, of the bacterial signaling molecule cyclic
      diguanosine monophosphate (c-di-GMP) are reported. The key intermediate, obtained
      in nine steps, is a 3'-amino-5'-azido-3',5'-dideoxy derivative. The 5'-azide
      serves as a masked amine from which the amine is obtained by Staudinger
      reduction, while the 3'-amine is converted to an isothiocyanate that, while
      stable to chromatography, and Staudinger conditions, nevertheless reacts well
      with the 5'-amine. 

PMID- 24313313
TI  - Orthography facilitates vocabulary learning for children with autism spectrum
      disorders (ASD).
AB  - This study investigated the extent to which children with autism spectrum
      disorders (ASD) can use orthography to facilitate vocabulary learning, as is the
      case for typically developing (TD) children. Forty-one children aged 7-12 years,
      20 with a formal diagnosis of ASD and 21 TD peers, were taught 16 low-frequency
      concrete science words, such as "breccia". Half of the stimuli had the written
      word presented alongside a picture of the target item (orthography present: OP)
      while the remaining items were taught with orthography absent (OA). During the
      learning phase, eye movements were recorded; there were no group differences in
      the time spent fixating the written form. Production, comprehension, and
      recognition of orthographic forms of new words were assessed immediately after
      learning and again after a 24-hour delay. The vocabulary learning of both groups
      was facilitated by the presence of orthography. Overall, the groups did not
      differ in comprehension of new words or recognition of new orthographic forms,
      although the children with ASD demonstrated superior phonological learning (as
      measured by a picture naming task) relative to TD peers. Additionally, both
      groups retained or increased new knowledge after 24 hours. The results suggest
      that presenting the written form during oral vocabulary teaching will enhance
      learning and provide a mechanism for children with ASD to increase word knowledge
      despite potential limitations in social learning.

PMID- 24313310
TI  - High-density lipoproteins for the systemic delivery of short interfering RNA.
AB  - INTRODUCTION: RNA interference (RNAi) is a powerful mechanism for gene silencing
      with the potential to greatly impact the development of new therapies for many
      human diseases. Short interfering RNAs (siRNAs) may be the ideal molecules for
      therapeutic RNAi. However, therapeutic siRNAs face significant challenges that
      must be overcome prior to widespread clinical use. Many efforts have been made to
      overcome the hurdles associated with systemic administration of siRNA; however,
      current approaches are still limited. As such, there is an urgent need to develop
      new strategies for siRNA delivery that have the potential to impact a broad
      spectrum of systemic diseases. AREAS COVERED: This review focuses on the promise
      of siRNA therapies and highlights current siRNA delivery methods. With an eye
      toward new strategies, this review first introduces high-density lipoprotein
      (HDL) and describes its natural biological functions, and then transitions into
      how HDLs may provide significant opportunities as next-generation siRNA delivery
      vehicles. Importantly, this review describes how synthetic HDLs leverage the
      natural ability of HDL to stabilize and deliver siRNAs. EXPERT OPINION: HDLs are
      natural nanoparticles that are critical to understanding the systemic delivery of
      therapeutic nucleic acids, like siRNA. Methods to synthesize biomimetic HDLs are
      being explored, and data demonstrate that this type of delivery vehicle may be
      highly beneficial for targeted and efficacious systemic delivery of siRNAs.

PMID- 24313314
TI  - Specificity of growth inhibitors and their cooperative effects in calcium oxalate
      monohydrate crystallization.
AB  - The molecular recognition and interactions governing site-specific adsorption of
      growth inhibitors on crystal surfaces can be tailored in order to control the
      anisotropic growth rates and physical properties of crystalline materials. Here
      we examine this phenomenon in calcium oxalate monohydrate (COM) crystallization,
      a model system of calcification with specific relevance for pathological
      mineralization. We analyzed the effect of three putative growth inhibitors-
      chondroitin sulfate, serum albumin, and transferrin--using analytical techniques
      capable of resolving inhibitor-crystal interactions from interfacial to bulk
      scales. We observed that each inhibitor alters surface growth by adsorbing on to
      distinct steps emanating from screw dislocations on COM surfaces. Binding of
      inhibitors to different crystallographic faces produced morphological
      modifications that are consistent with classical mechanisms of layer-by-layer
      crystal growth inhibition. The site-specific adsorption of inhibitors on COM
      surfaces was confirmed by bulk crystallization, fluorescent confocal microscopy,
      and atomic force microscopy. Kinetic studies of COM growth at varying inhibitor
      concentrations revealed marked differences in their efficacy and potency.
      Systematic analysis of inhibitor combinations, quantified via the combination
      index, identified various binary pairings capable of producing synergistic,
      additive, and antagonistic effects. Collectively, our investigation of
      physiologically relevant biomolecules suggests potential roles of COM inhibitors
      in pathological crystallization and provides guiding principles for biomimetic
      design of molecular modifiers for applications in crystal engineering.

PMID- 24313315
TI  - Dab1 and reelin participate in a common signal pathway that controls intestinal
      crypt/villus unit dynamics.
AB  - BACKGROUND INFORMATION: The myofibroblasts placed underneath the epithelium of
      the rodent small intestine express reelin, and the reelin absence modifies both
      the morphology and the cell renewal processes of the crypt-villus unit. In the
      developing central nervous system, the reelin effects are mediated by the
      disabled-1 (Dab1) protein. The present work explores whether Dab1 mediates the
      reelin control of the crypt-villus unit dynamics by examining in the mouse small
      intestine the consequences of the absence of (i) Dab1 (scrambler mutation) on
      crypt-villus unit cell renewal processes and morphology and (ii) reelin (reeler
      mutation) on the intestinal expression of Dab1. RESULTS: The effects of the
      scrambler mutation on the crypt-villus unit renewal processes are remarkably
      similar to those caused by the lack of reelin. Thus, both mutations significantly
      reduce epithelial cell proliferation, migration and apoptosis, and the number of
      Paneth cells; affect the morphology of the villus, and expand the intercellular
      space of the adherens junctions and desmosomes. The Western blot assays reveal
      that the Dab1 isoform present in the enterocytes has a molecular weight of ~63
      kDa and that in the brain of ~82 kDa. They also reveal that the absence of reelin
      increases Dab1 abundance in both brain and enterocytes. CONCLUSIONS: All
      together, the current findings link reelin with Dab1 and suggest that Dab1
      functions downstream of reelin action on the homeostasis of the crypt-villus
      unit.

PMID- 24313316
TI  - Relational and conjunctive binding functions dissociate in short-term memory.
AB  - Remembering complex events requires binding features within unified objects
      (conjunctions) and holding associations between objects (relations). Recent
      studies suggest that the two functions dissociate in long-term memory (LTM). Less
      is known about their functional organization in short-term memory (STM). The
      present study investigated this issue in patient AE affected by a stroke which
      caused damage to brain regions known to be relevant for relational functions both
      in LTM and in STM (i.e., the hippocampus). The assessment involved a battery of
      standard neuropsychological tasks and STM binding tasks. One STM binding task
      (Experiment 1) presented common objects and common colors forming either pairs
      (relations) or integrated objects (conjunctions). Free recall of relations or
      conjunctions was assessed. A second STM binding task used random polygons and non
      primary colors instead (Experiment 2). Memory was assessed by selecting the
      features that made up the relations or the conjunctions from a set of single
      polygons and a set of single colors. The neuropsychological assessment revealed
      impaired delayed memory in AE. AE's pronounced relational STM binding deficits
      contrasted with his completely preserved conjunctive binding functions in both
      Experiments 1 and 2. Only 2.35% and 1.14% of the population were expected to have
      a discrepancy more extreme than that presented by AE in Experiments 1 and 2,
      respectively. Processing relations and conjunctions of very elementary nonspatial
      features in STM led to dissociating performances in AE. These findings may inform
      current theories of memory decline such as those linked to cognitive aging. 

PMID- 24313317
TI  - Middle East respiratory syndrome coronavirus not detected in children
      hospitalized with acute respiratory illness in Amman, Jordan, March 2010 to
      September 2012.
AB  - Hospitalized children < 2 years of age in Amman, Jordan, admitted for fever
      and/or respiratory symptoms, were tested for Middle East respiratory syndrome
      coronavirus (MERS-CoV): MERS-CoV by real-time RT-PCR (rRT-PCR). This was a
      prospective year-round viral surveillance study in children <2 years of age
      admitted with acute respiratory symptoms and/or fever from March 2010 to
      September 2012 and enrolled from a government-run hospital, Al-Bashir in Amman,
      Jordan. Clinical and demographic data, including antibiotic use, were collected.
      Combined nasal/throat swabs were collected, aliquoted, and frozen at -80 degrees
      C. Specimen aliquots were shipped to Vanderbilt University and the Centers for
      Disease Control and Prevention (CDC), and tested by rRT-PCR for MERS-CoV. Of the
      2433 subjects enrolled from 16 March 2010 to 10 September 2012, 2427 subjects had
      viral testing and clinical data. Of 1898 specimens prospectively tested for other
      viruses between 16 March 2010 and 18 March 2012, 474 samples did not have other
      common respiratory viruses detected. These samples were tested at CDC for MERS
      CoV and all were negative by rRT-PCR for MERS-CoV. Of the remaining 531 samples,
      collected from 19 March 2012 to 10 September 2012 and tested at Vanderbilt, none
      were positive for MERS-CoV. Our negative findings from a large sample of young
      Jordanian children hospitalized with fever and/or respiratory symptoms suggest
      that MERS-CoV was not widely circulating in Amman, Jordan, during the 30-month
      period of prospective, active surveillance occurring before and after the first
      documented MERS-CoV outbreak in the Middle East region.

PMID- 24313318
TI  - A simplified method to screen for in-vivo performance of oral lipid formulations.
AB  - OBJECTIVES: To develop a simplified in-vitro screening method for oral lipid
      based formulations using intestinal biorelevant media including lipolysis, as an
      alternative to pH-stat lipolysis models. METHOD: Fasting state simulated
      intestinal fluid version 2 (FaSSIF-V2) and early fed state simulated intestinal
      fluid (FeSSIF) were modified for use in a simplified lipolysis screening method.
      This screening method consists of the following steps: dispersion of the lipid
      formulation in biorelevant media; incubation of dispersions on an orbital shaker
      for 60 min at 37 degrees C; ultracentrifugation of dispersions and drug assay of
      supernatants. This method was evaluated using four lipid-based formulations
      containing danazol, which had previously been assessed by in-vitro pH-stat
      lipolysis and compared in an in-vivo study in dogs. KEY FINDINGS: Biorelevant
      media were modified under consideration of both physiological and practical
      aspects, including adjustment of the pH to 6.5, the addition of calcium ions and
      the addition of 100 U/ml porcine pancreatin to enable lipolysis of a test
      formulation. Using a modified FaSSIF-V2, the same rank order in performance of
      four danazol formulations as previously observed in a pH-stat model was observed,
      and these results also reflected the in-vivo study results. The results in
      modified early FeSSIF suggested that there would be a change in the rank order of
      formulation performance in the fed state compared with the fasted state. By
      comparing the formulation behaviour in the presence and absence of pancreatin, it
      was concluded that dispersion is more important than lipolysis for precipitation
      from the formulation in the fasted state, but that lipolysis is predicted to
      increase in relevance in the fed state. CONCLUSION: The new, simplified method
      for lipolysis enables a more efficient screening for the in-vivo performance of
      lipid formulations in the fasted state and enables a prediction of formulation
      behaviour in both the fed and fasted states. An additional advantage of the
      method is that the relative influence of lipolysis and dispersion on drug release
      can be directly compared.

PMID- 24313319
TI  - Pretransplant C-reactive protein as A prognostic marker in allogeneic stem cell
      transplantation.
AB  - We evaluated the prognostic role of baseline levels of C-reactive protein (CRP)
      as well as CRP levels during conditioning in patients undergoing myeloablative
      allogeneic stem cell transplantation (SCT). Furthermore, we studied the impact of
      baseline clinical factors and conditioning regimens on CRP levels in the same
      period. We conducted a population-based retrospective study of 349 patients
      undergoing SCT at the National Danish SCT centre between January 2000 and January
      2009. CRP levels increased significantly during the conditioning and peaked at
      day -3 before infusion of the graft. Elevated CRP was associated with older age,
      non-malignant disease, reduced pretransplant Karnofsky score and high-risk
      leukaemia. By univariate and multivariate analyses, increased CRP levels (>10
      mg/l) before the start of treatment (day -7) and at the day of graft infusion
      (day 0) were associated with decreased overall survival [HR 1.35 (95%CL) (1.18
      1.54); P < 0.0001] and increased treatment-related mortality [1.5 (1.24-1.82); P
      < 0.0001]. Similar findings were seen for mean CRP levels during the
      conditioning. CRP was not associated with risk of relapse or aGvHD in
      multivariate analysis. This study suggests that increased CRP levels before and
      during the conditioning are associated with baseline clinical factors and that
      elevated pretransplant CRP levels predict a poorer survival in SCT. 

PMID- 24313321
TI  - Potentially perilous pedagogies: teaching trauma is not the same as trauma
      informed teaching.
AB  - This article explores why and how trauma theory and research are currently used
      in higher education in nonclinical courses such as literature, women's studies,
      film, education, anthropology, cultural studies, composition, and creative
      writing. In these contexts, traumatic material is presented not only indirectly
      in the form of texts and films that depict traumatic events but also directly in
      the form of what is most commonly referred to in nonclinical disciplines as
      trauma studies, cultural trauma studies, and critical trauma studies. Within
      these areas of study, some instructors promote potentially risky pedagogical
      practices involving trauma exposure or disclosure despite indications that these
      may be having deleterious effects. After examining the published rationales for
      such methods, we argue that given the high rates of trauma histories (66%-85%),
      posttraumatic stress disorder (9%-12%), and other past event-related distress
      among college students, student risk of retraumatization and secondary
      traumatization should be decreased rather than increased. To this end, we propose
      that a trauma-informed approach to pedagogy-one that recognizes these risks and
      prioritizes student emotional safety in learning-is essential, particularly in
      classes in which trauma theories or traumatic experiences are taught or
      disclosed. 

PMID- 24313322
TI  - beta-Cyclodextrin-bearing gold glyconanoparticles for the development of site
      specific drug delivery systems.
AB  - Three novel gold nanoparticles containing multiple long, flexible linkers
      decorated with lactose, beta-cyclodextrin, and both simultaneously have been
      prepared. The interaction of such nanoparticles with beta-d-galactose-recognizing
      lectins peanut agglutinin (PNA) and human galectin-3 (Gal-3) was demonstrated by
      UV-vis studies. Gal-3 is well-known to be overexpressed in several human tumors
      and can act as a biorecognizable target. This technique also allowed us to
      estimate their loading capability toward the anticancer drug methotrexate (MTX).
      Both results make these glyconanoparticles potential site-specific delivery
      systems for anticancer drugs. 

PMID- 24313320
TI  - Protein kinase inhibitors in the treatment of inflammatory and autoimmune
      diseases.
AB  - Protein kinases mediate protein phosphorylation, which is a fundamental component
      of cell signalling, with crucial roles in most signal transduction cascades: from
      controlling cell growth and proliferation to the initiation and regulation of
      immunological responses. Aberrant kinase activity is implicated in an increasing
      number of diseases, with more than 400 human diseases now linked either directly
      or indirectly to protein kinases. Protein kinases are therefore regarded as
      highly important drug targets, and are the subject of intensive research
      activity. The success of small molecule kinase inhibitors in the treatment of
      cancer, coupled with a greater understanding of inflammatory signalling cascades,
      has led to kinase inhibitors taking centre stage in the pursuit for new anti
      inflammatory agents for the treatment of immune-mediated diseases. Herein we
      discuss the main classes of kinase inhibitors; namely Janus kinase (JAK), mitogen
      activated protein kinase (MAPK) and spleen tyrosine kinase (Syk) inhibitors. We
      provide a mechanistic insight into how these inhibitors interfere with kinase
      signalling pathways and discuss the clinical successes and failures in the
      implementation of kinase-directed therapeutics in the context of inflammatory and
      autoimmune disorders. 

PMID- 24313323
TI  - The successful recovery of low copy number and degraded DNA from bones exposed to
      seawater suitable for generating a DNA STR profile.
AB  - A universal method allowing for DNA profiling from bones exposed to seawater has
      not been reported yet. This study refers on the identification of a body immersed
      in seawater for 8 months. The biological material for identification was the
      mandibular body, usually characterized by low success rates of DNA analysis.
      Initially, two extraction protocols were performed with negative results: one
      used for bones immersed in fresh water and a silica-column procedure. A third
      protocol was performed, which combined the extraction of a higher amount of bone
      powder, the use of multi-silica-based extraction columns followed by a
      concentration step. This protocol allowed to obtain low copy number DNA and to
      generate a 12-loci STR profile by combining conventional STR typing and mini-STR
      technologies. This protocol could be suitable when human bones have been exposed
      to severe environmental conditions, and the available nuclear DNA is highly
      degraded and in low copy number. 

PMID- 24313324
TI  - Effects of growth differentiation factor 9 and bone morphogenetic protein 15 on
      the in vitro maturation of porcine oocytes.
AB  - Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15)
      are members of the transforming growth factor-beta (TGF-beta) family, and their
      roles in oocyte maturation and cumulus expansion are well known in the mouse and
      human, but not in the pig. We investigated GDF9 and BMP15 expressions in porcine
      oocytes during in vitro maturation. A significant increase in the mRNA levels of
      GDF9 and BMP15 was observed at germinal vesicle breakdown, with expression levels
      peaking at metaphase I (MI), but decreasing at metaphase II (MII). GDF9 and BMP15
      protein localized to the oocyte cytoplasm. While treatment with GDF9 and BMP15
      increased the expression of genes involved in both oocyte maturation (c-mos,
      cyclinb1 and cdc2) and cumulus expansion (has2, ptgs2, ptx3 and tnfaip6),
      SB431542 (a TGFbeta-GDF9 inhibitor) decreased meiotic maturation at MII.
      Following parthenogenetic activation, the percentage of blastocysts in SB431542
      treatment was lower than in the control (41.3% and 74.4%, respectively).
      Treatment with GDF9 and BMP15 also increased the mRNA levels of maternal genes
      such as c-mos [a regulatory subunit of mitogen-activated protein kinase (MAPK)],
      and cyclinb1 and cdc2 [regulatory subunits of maturation/M-phase-promoting factor
      (MPF)]; however, SB431542 significantly decreased their mRNA levels. These data
      were supported by poly (A)-test PCR and protein activity analyses. Our results
      show that GDF9 and BMP15 participate in cumulus expansion and that they stimulate
      MPF and MAPK activities in porcine oocytes during in vitro maturation. 

PMID- 24313326
TI  - Correlation between surface chemistry and settlement behaviour in barnacle
      cyprids (Balanus improvisus).
AB  - In laboratory-based biofouling assays, the influence of physico-chemical surface
      characteristics on barnacle settlement has been tested most frequently using the
      model organism Balanus amphitrite (= Amphibalanus amphitrite). Very few studies
      have addressed the settlement preferences of other barnacle species, such as
      Balanus improvisus (= Amphibalanus improvisus). This study aimed to unravel the
      effects of surface physico-chemical cues, in particular surface-free energy (SFE)
      and surface charge, on the settlement of cyprids of B. improvisus. The use of
      well-defined surfaces under controlled conditions further facilitates comparison
      of the results with recent similar data for B. amphitrite. Zero-day-old cyprids
      of B. improvisus were exposed to a series of model surfaces, namely self
      assembled monolayers (SAMs) of alkanethiols with varying end-groups, homogenously
      applied to gold-coated polystyrene (PS) Petri dishes. As with B. amphitrite,
      settlement of cyprids of B. improvisus was influenced by both SFE and charge,
      with higher settlement on low-energy (hydrophobic) surfaces and negatively
      charged SAMs. Positively charged SAMs resulted in low settlement, with
      intermediate settlement on neutral SAMs of similar SFE. In conclusion, it is
      demonstrated that despite previous suggestions to the contrary, these two species
      of barnacle show similar preferences in response to SFE; they also respond
      similarly to charge. These findings have positive implications for the
      development of novel antifouling (AF) coatings and support the importance of
      consistency in substratum choice for assays designed to compare surface
      preferences of fouling organisms. 

PMID- 24313325
TI  - A digital evaluation of alveolar ridge preservation at implants placed
      immediately into extraction sockets: an experimental study in the dog.
AB  - OBJECTIVE: To compare with pristine sites bone resorption and soft tissue
      adaptation at implants placed immediately into extraction sockets (IPIES) in
      conjunction with deproteinized bovine bone mineral (DBBM) particles and a
      collagen membrane. MATERIAL AND METHODS: The mesial root of the third premolar in
      the left side of the mandible was endodontically treated (Test). Flaps were
      elevated, the tooth hemi-sectioned, and the distal root removed to allow the
      immediate installation of an implant into the extraction socket in a lingual
      position. DBBM particles were placed into the defect and on the outer contour of
      the buccal bony ridge, concomitantly with the placement of a collagen membrane. A
      non-submerged healing was allowed. The premolar on the right side of the mandible
      was left in situ (control). Ground sections from the center of the implant as
      well as from the center of the distal root of the third premolar of the opposite
      side of the mandible were obtained. The histological image from the implant site
      was superimposed to that of the contralateral pristine distal alveolus, and
      dimensional variation evaluated for the hard tissue and the alveolar ridge.
      RESULTS: After 3 months of healing, both histological and photographic evaluation
      revealed a reduction of hard and soft tissue dimensions. CONCLUSION: The contour
      augmentation performed with DBBM particles and a collagen membrane at the buccal
      aspects of implants placed IPIES was not able to maintain the tissue volume.

PMID- 24313327
TI  - Fluorohydrogenate cluster ions in the gas phase: electrospray ionization mass
      spectrometry of the [1-ethyl-3-methylimidazolium(+)][F(HF)2.3(-)] ionic liquid.
AB  - Electrospray ionization of the fluorohydrogenate ionic liquid [1-ethyl-3
      methylimidazolium][F(HF)2.3] ionic liquid was conducted to understand the nature
      of the anionic species as they exist in the gas phase. Abundant fluorohydrogenate
      clusters were produced; however, the dominant anion in the clusters was [FHF(-)],
      and not the fluoride-bound HF dimers or trimers that are seen in solution.
      Density functional theory (DFT) calculations suggest that HF molecules are bound
      to the clusters by about 30 kcal/mol. The DFT-calculated structures of the [FHF(
      )]-bearing clusters show that the favored interactions of the anions are with the
      methynic and acetylenic hydrogen atoms on the imidazolium cation, forming planar
      structures similar to those observed in the solid state. A second series of
      abundant negative ions was also formed that contained [SiF5(-)] together with the
      imidazolium cation and the fluorohydrogenate anions that originate from reaction
      of the spray solution with silicate surfaces. 

PMID- 24313328
TI  - Identifying Zn-bound histidine residues in metalloproteins using hydrogen
      deuterium exchange mass spectrometry.
AB  - In this work, we have developed a method that uses hydrogen-deuterium exchange
      (HDX) of C2-hydrogens of histidines coupled with mass spectrometry (MS) to
      identify Zn-bound histidines in metalloproteins. This method relies on
      differences in HDX reaction rates of Zn-bound and Zn-free His residues. Using
      several model peptides and proteins, we find that all Zn-bound His residues have
      substantially lower HDX reaction rates in the presence of the metal. The vast
      majority of non-Zn-binding His residues undergo no significant changes in HDX
      reaction rates when their reactivity is compared in the presence and absence of
      Zn. Using this new approach, we then determined the Zn binding site of beta-2
      microglobulin, a protein associated with metal-induced amyloidosis. Together,
      these results suggest that HDX-MS of His C2-hydrogens is a promising new method
      for identifying Zn-bound histidines in metalloproteins. 

PMID- 24313329
TI  - A roller coaster of emotions and sense--coping with the perceived psychosocial
      consequences of a false-positive screening mammography.
AB  - AIMS AND OBJECTIVES: To explore coping with the perceived psychosocial
      consequences of a false-positive screening mammography. BACKGROUND: Mammographic
      screening has been found effective to decrease breast cancer (BC) mortality, yet
      there are adverse effects. Psychosocial consequences of false-positive
      mammographic screening have mainly been investigated from a population-based
      perspective. A call for qualitative studies to further explore these consequences
      has thus been postulated. To date, qualitative studies have elucidated women's
      experiences following their recall breast examinations, but their coping with
      perceived psychosocial consequences of a false-positive screening mammography has
      not yet been explored. DESIGN: An explorative qualitative study. METHODS: Face-to
      face interviews were held with a purposive heterogeneous sample of 13 Swedish
      speaking women with a false-positive screening mammography. The transcripts were
      analysed by the use of an inductive content analysis. RESULTS: Coping with the
      perceived psychosocial consequences of a false-positive screening mammography
      implied a roller coaster of emotion and sense. Women described how they imagined
      the worst and were in a state of uncertainty feeling threatened by a fatal
      disease. Conversely, they felt protected, surrounded by their families and being
      professionally taken care of, which together with perceived sisterhood and self
      empowerment evoked strength and hope. Being aware of family responsibility became
      a crucial matter. Experiencing false-positive screening raised thoughts of
      thankfulness and reappraisal of life, although an ounce of BC anxiety remained.
      Consequently, gained awareness about BC screening and values in life surfaced.
      CONCLUSIONS: Experiencing a false-positive screening mammography triggers
      agonising experiences evoking a variety of coping strategies. Provision of
      screening raises the issue of responsibility for an impact on psychosocial well
      being among healthy women. RELEVANCE TO CLINICAL PRACTICE: Gained knowledge might
      provide a basis for interventions to prevent psychosocial consequences of false
      positive mammographic screening and provide support for women with a potentially
      compromised ability to overcome such consequences.

PMID- 24313330
TI  - Identification of two novel Prodelphinidin A-type dimers from roasted hazelnut
      skins ( Corylus avellana L.).
AB  - Two new A-type dimeric prodelphinidins, EGC-(2beta->O7, 4beta->8)-C and EGC
      (2beta->O5, 4beta->6)-C, were isolated from the skins of roasted hazelnut (
      Corylus avellana L.) by low-speed rotary countercurrent chromatography (LSRCCC)
      and final purification by preparative HPLC. Their structures were determined by a
      combination of mass spectrometry (HPLC-ESI-MS(n) and HR-ESI-MS) and NMR
      spectroscopy that included the application of 2D methods ((1)H-(1)H COSY, HSQC,
      HMBC, and NOESY). Furthermore, circular dichroism (CD) and acid-catalyzed
      degradation (phloroglucinolysis) confirmed the proposed structures. 

PMID- 24313331
TI  - Tosedostat for the treatment of relapsed and refractory acute myeloid leukemia.
AB  - INTRODUCTION: Despite recent improvements in the scientific understanding of
      leukemia biology, the overall prognosis for adults with acute myeloid leukemia
      (AML) remains disappointingly poor. Therapeutic options for AML that are relapsed
      or refractory to front-line chemotherapy are limited, and the development of
      effective agents for this indication is an unmet need. The aminopeptidase
      inhibitor tosedostat (CHR-2797) is a novel metalloenzyme inhibitor that blocks a
      critical step in the protein degradation and re-synthesizes intracellular
      pathway. This orally bioavailable agent has shown promising activity in vitro and
      in early clinical trials for patients with relapsed/refractory AML. AREAS
      COVERED: This review summarizes the development of tosedostat to date.
      Specifically, the authors review the literature on its mechanism of action,
      pharmacoepidemiology and the currently available preclinical and clinical data.
      EXPERT OPINION: Tosedostat is an oral agent with a novel mechanism of action.
      Early trials of tosedostat in relapsed/refractory elderly AML have shown
      encouraging results in a population with an overall very poor prognosis. This is
      particularly noted in patients with a prior history of myelodysplastic syndrome
      (MDS) and hypomethylating-agent (HMA) use. Additional studies of tosedostat in
      rationally designed combinations with cytarabine and HMAs in advanced MDS and
      refractory AML populations are ongoing. Furthermore, the safety and efficacy
      evaluation is similarly ongoing, and patient selection will be an important
      consideration in the continued development of this promising compound.

PMID- 24313332
TI  - Melatonin synthesis in rice seedlings in vivo is enhanced at high temperatures
      and under dark conditions due to increased serotonin N-acetyltransferase and N
      acetylserotonin methyltransferase activities.
AB  - Temperature and light are important environmental factors for plant growth and
      development. The final two enzymes in the melatonin synthesis pathway in plants
      are serotonin N-acetyltransferase (SNAT) and N-acetylserotonin methyltransferase
      (ASMT), which have thermophilic characteristics. Thus, the effects of temperature
      and light on melatonin synthesis in rice seedlings were investigated. Here, we
      demonstrated that melatonin levels increased as temperature increased when rice
      seedlings were exposed to various temperatures for 1 hr. Moreover, the relative
      melatonin levels were higher in the dark. For example, exposure of rice seedlings
      to 1-hr darkness at 55 degrees C resulted in a melatonin yield of 4.9 ng/g fresh
      weight (fw), compared with 2.95 ng/g fw under light conditions. Temperature
      dependent melatonin synthesis was closely associated with an increase in both
      SNAT and ASMT activities, but not with transcript levels of melatonin
      biosynthetic genes. The daily melatonin levels in field-grown rice plants were
      unaffected as the positive effect of the relatively high temperature during the
      day was counteracted by the negative effect of the high light. The opposite
      effect occurred during the night, in which the positive effect of darkness on
      melatonin synthesis was counteracted by the negative effect of a low temperature.

PMID- 24313333
TI  - The effectiveness of specialist neuroscience care in severe traumatic brain
      injury: a systematic review.
AB  - BACKGROUND: UK trauma services are currently undergoing reconfiguration, but the
      optimum management pathway for head-injured patients is uncertain. We therefore
      performed a systematic review to assess the effects of routine inter-hospital
      transfer and specialist neuroscience care on mortality and disability in patients
      with non-surgical severe traumatic brain injury injured nearest to a non
      specialist acute hospital. METHODS: A protocol was registered with PROSPERO
      (CRD42012002021) and review methodology followed Cochrane Collaboration
      recommendations. A peer reviewed search strategy was implemented in an exhaustive
      range of information sources, including all major bibliographic databases,
      between 1973 and July 2013. Selection of eligible studies, extraction of relevant
      data and bias assessment were then performed by two independent reviewers. In the
      absence of homogeneous effect estimates at low risk of bias a narrative synthesis
      was pre-specified. RESULTS: Four cohort studies, including a total of 4688
      patients, were identified as potentially eligible after screening and bias
      assessment. Confounding by indication, arising from selective transfer of less
      severely injured patients, was the main limitation of included studies, with
      overall risk of bias rated as high for both mortality and disability effect
      estimates. Adjusted odds ratios for mortality favoured secondary transfer,
      ranging from 1.92 (95% CI 1.25-2.95) to 2.09 (95% CI 1.59-2.74). No convincing
      association was observed between non-specialist care and unfavourable outcome
      with a conditional odds ratio of 1.13 (95% CI 0.36-3.6). CONCLUSIONS: There is
      limited evidence supporting a strategy of secondary transfer of severe non
      surgical traumatic brain injury patients to specialist neuroscience centres.
      Randomised controlled trials powered to detect clinically plausible treatment
      effects should be considered to definitively investigate effectiveness.

PMID- 24313334
TI  - Enhanced light harvesting in dye-sensitized solar cells coupled with titania
      nanotube photonic crystals: a theoretical study.
AB  - Herein we present a theoretical analysis on the optical properties and the
      photocurrent enhancement of nanotube-based dye-sensitized solar cells (DSSCs)
      coupled with a TiO2 nanotube (NT) photonic crystal (PC). It is found that the
      introduction of a TiO2 nanotube PC produces both Bragg mirror effect and Fabry
      Perot cavity behavior, leading to a significant enhancement of light harvesting
      for photons in the photonic bandgap and at the two band edges. In addition, an
      increased amount of surface-anchored dye due to the larger surface area in the NT
      PC layer also causes absorption enhancement in the whole visible spectrum. The
      effects of structural parameters of the PC, such as the thickness of the PC
      layer, the axial lattice constant, the diameter of the nanotube, and light
      incident angle, on the optical properties and photocurrent magnification are
      thoroughly studied. The optimum structural parameters are proposed, which not
      only provide guidance but also offer further opportunities in the design and
      applications of TiO2 nanotube photonic crystals. 

PMID- 24313335
TI  - Hyperpolarized xenon-based molecular sensors for label-free detection of
      analytes.
AB  - Nuclear magnetic resonance (NMR) can reveal the chemical constituents of a
      complex mixture without resorting to chemical modification, separation, or other
      perturbation. Recently, we and others have developed magnetic resonance agents
      that report on the presence of dilute analytes by proportionately altering the
      response of a more abundant or easily detected species, a form of amplification.
      One example of such a sensing medium is xenon gas, which is chemically inert and
      can be optically hyperpolarized, a process that enhances its NMR signal by up to
      5 orders of magnitude. Here, we use a combinatorial synthetic approach to produce
      xenon magnetic resonance sensors that respond to small molecule analytes. The
      sensor responds to the ligand by producing a small chemical shift change in the
      Xe NMR spectrum. We demonstrate this technique for the dye, Rhodamine 6G, for
      which we have an independent optical assay to verify binding. We thus demonstrate
      that specific binding of a small molecule can produce a xenon chemical shift
      change, suggesting a general approach to the production of xenon sensors targeted
      to small molecule analytes for in vitro assays or molecular imaging in vivo. 

PMID- 24313336
TI  - Neural correlates of clinical improvement after deep transcranial magnetic
      stimulation (DTMS) for treatment-resistant depression: a case report using
      functional magnetic resonance imaging.
AB  - We report the effects of a 4-week trial of deep transcranial magnetic stimulation
      (DTMS) on depressive and anxious symptoms and brain activity in a patient (Mrs A)
      with treatment-resistant depression (TRD). The protocol involved a pre- and a
      post-functional magnetic resonance imaging (fMRI) scan during which Mrs A had to
      perform a working memory task (i.e., n-back). Her baseline score on the 21-item
      Hamilton Depression Rating Scale (HAM-D21) was 24, indicating severe depressive
      symptoms. Immediately after 4 weeks of daily DTMS treatment applied over the left
      dorsolateral prefrontal cortex (DLPFC), her HAM-D21 score decreased to 13 (a 46%
      reduction), and 1 month later, it was 12 (a 50% reduction). Moreover, Mrs A's
      accuracy scores on the n-back task (i.e., 2-back condition) improved from 79%
      (baseline) to 96% (after DTMS treatment). At the neural level, Mrs A showed
      significantly increased brain activity in the working memory network (e.g.,
      DLPFC, parietal cortex) during the execution of the 2-back condition after DTMS
      treatment compared to baseline. 

PMID- 24313337
TI  - Potential of birds to serve as a pathology-free model of type 2 diabetes, Part 1:
      Is the apparent absence of the rage gene a factor in the resistance of avian
      organisms to chronic hyperglycemia?
AB  - Diabetes mellitus is a global pandemic that accounts for ever-increasing rates of
      morbidity and mortality and consumes a growing share of national health care
      budgets. In spite of concerted efforts, a solution to this problem has not yet
      been found. One reason for this situation is lack of good animal models. Such
      models have been used successfully in many areas of biomedical research, but they
      have proven less than satisfactory in studies on diabetic complications. In this
      article, we propose to supplement traditional animal models of diabetes that use
      longitudinal, prospective studies of sick animals (mammals) with
      retrospective/comparative investigations of healthy animals (birds). Avians are
      promising models for such studies because they live healthy lives with chronic
      hyperglycemia that would be fatal to humans. We outline the advantages of the new
      perspective and show how, by implementing this approach, we observed that birds
      appear to be missing an important gene linked to diabetic complications. The
      protein encoded by this gene is a receptor for advanced glycation end products
      (RAGEs). Although the absence of RAGEs from birds has yet to be confirmed at the
      protein level, other differences between humans and birds may also be important
      in accounting for the ability of birds to live with chronic hyperglycemia. Two
      such additional such characteristics are currently being explored, and it is
      probable that more will emerge in time. We believe that the proposed perspective
      may improve the understanding of diabetes mellitus and may help in developing new
      means for controlling and preventing diabetic complications.

PMID- 24313338
TI  - Mass spectrometric studies of reductive elimination from Pd(IV) complexes.
AB  - Reductive elimination of ethane from the palladium(IV) complex [PdMe3(bpy)I] (bpy
      = 2,2'-bipyridine) is studied by electrospray ionization mass spectrometry.
      Palladium(IV) complexes can be detected as binuclear clusters [Pd2Me6I(bpy)2](+)
      or as complexes [PdMe3(bpy)(L)](+) stabilized by an electron-donating ligand L.
      Fragmentation of all palladium(IV) complexes is dominated by elimination of
      ethane which corresponds to the reductive elimination coupling of the methyl
      groups. The associated energy demands for different complexes reveal that the
      mononuclear complexes with poorly electron-donating ligands provide the fastest
      reaction. 

PMID- 24313340
TI  - Inhibition of antithrombin and bovine serum albumin native state aggregation by
      heparin.
AB  - Protein native state aggregation, a major problem in pharmaceutical and
      biological processes, has been addressed pharmacologically by the addition of
      protein-binding excipients. Heparin (Hp), a highly sulfated polysaccharide,
      interacts with numerous proteins with moderate to high affinity, but reports
      about its effect on protein aggregation are contradictory. We studied the pH
      dependence of the aggregation of antithrombin (AT) and bovine serum albumin (BSA)
      in the presence and absence of heparin. High-precision turbidimetry showed strong
      aggregation for both AT and BSA in I = 10 mM NaCl, conditions at which
      electrostatically driven Hp binding and aggregation both occur, with more obvious
      aggregation of heparin-free AT appearing as larger aggregate size. Aggregation of
      AT was dramatically inhibited at Hp: protein 6:1 (mole ratio); however, the
      effect at 0.5:1 Hp:protein was greater for BSA. Frontal analysis capillary
      electrophoresis showed a much larger equilibrium association constant Kobs
      between Hp and AT, in accord with the onset of Hp binding at a higher pH; both
      effects are explained by the higher charge density of the positive domain for AT
      as revealed by modeling with DelPhi. The corresponding modeling images showed
      that these domains persist at high salt only for AT, consistent with the 160-fold
      drop in Kobs at 100 mM salt for BSA-Hp binding. The smaller inhibition effect for
      AT arises from the tendency of its uncomplexed monomer to form larger aggregates
      more rapidly, but the stronger binding of Hp to AT does not facilitate Hp-induced
      aggregate dissolution which occurs more readily for BSA. This can be attributed
      to the higher density of AT aggregates evidenced by higher fractal dimensions.
      Differences between inhibition and reversal by Hp arise because the former may
      depend on the stage at which Hp enters the aggregation process and the latter on
      aggregate size and morphology. 

PMID- 24313339
TI  - Antibodies to influenza virus A/H1N1 hemagglutinin in Type 1 diabetes children
      diagnosed before, during and after the SWEDISH A(H1N1)pdm09 vaccination campaign
      2009-2010.
AB  - We determined A/H1N1-hemagglutinin (HA) antibodies in relation to HLA-DQ
      genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7-to
      18-year-old type 1 diabetes patients diagnosed April 2009-December 2010.
      Antibodies to (35) S-methionine-labelled A/H1N1 hemagglutinin were determined in
      a radiobinding assay in patients diagnosed before (n = 325), during (n = 355) and
      after (n = 461) the October 2009-March 2010 Swedish A(H1N1)pdm09 vaccination
      campaign, along with HLA-DQ genotypes and autoantibodies against GAD, insulin, IA
      2 and ZnT8 transporter. Before vaccination, 0.6% patients had A/H1N1-HA
      antibodies compared with 40% during and 27% after vaccination (P < 0.0001). In
      children <3 years of age, A/H1N1-HA antibodies were found only during
      vaccination. The frequency of A/H1N1-HA antibodies during vaccination decreased
      after vaccination among the 3 < 6 (P = 0.006) and 13 < 18 (P = 0.001), but not
      among the 6 < 13-year-olds. HLA-DQ2/8 positive children <3 years decreased from
      54% (15/28) before and 68% (19/28) during, to 30% (9/30) after vaccination (P =
      0.014). Regardless of age, DQ2/2; 2/X (n = 177) patients had lower frequency (P =
      0.020) and levels (P = 0.042) of A/H1N1-HA antibodies compared with non-DQ2/2;
      2/X (n = 964) patients. GADA frequency was 50% before, 60% during and 51% after
      vaccination (P = 0.009). ZnT8QA frequency increased from 30% before to 34% during
      and 41% after vaccination (P = 0.002). Our findings suggest that young (<3 years)
      along with DQ2/2; 2/X patients were low responders to Pandemrix((r)) . As the
      proportion of DQ2/8 patients <3 years of age decreased after vaccination and the
      frequencies of GADA and ZnT8QA were enhanced, it cannot be excluded that the
      vaccine affected clinical onset of type 1 diabetes. 

PMID- 24313341
TI  - Dopamine receptor agonists for Parkinson's disease.
AB  - INTRODUCTION: Prolonged administration of l-3,4-dihydroxyphenylalanine (l-DOPA)
      for Parkinson's disease (PD) is hampered by motor complications related to the
      progressive incapacity of residual nigrostriatal neurons to properly utilize the
      drug. Direct stimulation of dopaminergic (DAergic) receptors with specific
      compounds (DA agonists) has, therefore, become an additional therapeutic tool for
      PD. AREAS COVERED: DA agonists have considerable anti-parkinsonian symptomatic
      efficacy, although they are less potent than l-DOPA. This review summarizes pre
      clinical and clinical data on DA agonists and their role in treating PD. Specific
      focus was put on second-generation, first-line non-ergolinic DA agonists and
      their motor, non-motor and putative neuroprotective effects. The anti
      parkinsonian potential of recently developed DA agonists that reached Phase II
      and III clinical trials was also addressed. EXPERT OPINION: DA agonists can be
      useful along the whole natural course of PD, as monotherapy in the initial phase
      or combined with l-DOPA in advanced PD. Extended-release formulations have been
      developed for second-generation DA agonists, which are better appreciated by
      patients. Neuroprotective properties have been proposed for DA agonists, based on
      pre-clinical studies, but never convincingly demonstrated in patients. New DA
      agonists, with better symptomatic efficacy and devoid of the side effects that
      characterize current compounds, are needed.

PMID- 24313342
TI  - Infrared attenuated total reflection spectroscopy for the characterization of
      gold nanoparticles in solution.
AB  - In situ synthesis of bare gold nanoparticles mediated by stainless steel as
      reducing agent was monitored via infrared attenuated total reflection (IR-ATR)
      spectroscopy. Gold nanoparticles were directly synthesized within the liquid cell
      of the ATR unit taking immediate advantage of the stainless steel walls of the
      ATR cell. As nanoparticles were formed, a layer of particles was deposited at the
      SiO2 ATR waveguide surface. Incidentally, the absorption bands of water increased
      resulting from surface-enhanced infrared absorption (SEIRA) effects arising from
      the presence of the gold nanoparticles within the evanescent field. Next to the
      influence of the Au(III) precursor concentration and the temperature, the
      suitability of IR-ATR spectroscopy as an innovative tool for investigating
      changes of nanoparticles in solution, including their aggregation promoted by an
      increase of the ionic strength or via a pH decrease, and for detailing the
      sedimentation process of gold nanoparticles was confirmed. 

PMID- 24313343
TI  - Graphene oxide based theranostic platform for T1-weighted magnetic resonance
      imaging and drug delivery.
AB  - Magnetic resonance imaging (MRI) is a powerful and widely used clinical technique
      in cancer diagnosis. MRI contrast agents (CAs) are often used to improve the
      quality of MRI-based diagnosis. In this work, we developed a positive T1 MRI CA
      based on graphene oxide (GO)-gadolinium (Gd) complexes. In our strategy,
      diethylenetriaminepentaacetic acid (DTPA) is chemically conjugated to GO,
      followed by Gd(III) complexation, to form a T1 MRI CA (GO-DTPA-Gd). We have
      demonstrated that the GO-DTPA-Gd system significantly improves MRI T1 relaxivity
      and leads to a better cellular MRI contrast effect than Magnevist, a commercially
      used CA. Next, an anticancer drug, doxorubicin (DOX), was loaded on the surface
      of GO sheets via physisorption. Thus-prepared GO-DTPA-Gd/DOX shows significant
      cytotoxicity to the cancer cells (HepG2). This work provides a novel strategy to
      build a GO-based theranostic nanoplatform with T1-weighted MRI, fluorescence
      imaging, and drug delivery functionalities. 

PMID- 24313344
TI  - Protannotator: a semiautomated pipeline for chromosome-wise functional annotation
      of the "missing" human proteome.
AB  - The chromosome-centric human proteome project (C-HPP) aims to define the complete
      set of proteins encoded in each human chromosome. The neXtProt database
      (September 2013) lists 20,128 proteins for the human proteome, of which 3831
      human proteins (~19%) are considered "missing" according to the standard metrics
      table (released September 27, 2013). In support of the C-HPP initiative, we have
      extended the annotation strategy developed for human chromosome 7 "missing"
      proteins into a semiautomated pipeline to functionally annotate the "missing"
      human proteome. This pipeline integrates a suite of bioinformatics analysis and
      annotation software tools to identify homologues and map putative functional
      signatures, gene ontology, and biochemical pathways. From sequential BLAST
      searches, we have primarily identified homologues from reviewed nonhuman
      mammalian proteins with protein evidence for 1271 (33.2%) "missing" proteins,
      followed by 703 (18.4%) homologues from reviewed nonhuman mammalian proteins and
      subsequently 564 (14.7%) homologues from reviewed human proteins. Functional
      annotations for 1945 (50.8%) "missing" proteins were also determined. To
      accelerate the identification of "missing" proteins from proteomics studies, we
      generated proteotypic peptides in silico. Matching these proteotypic peptides to
      ENCODE proteogenomic data resulted in proteomic evidence for 107 (2.8%) of the
      3831 "missing proteins, while evidence from a recent membrane proteomic study
      supported the existence for another 15 "missing" proteins. The chromosome-wise
      functional annotation of all "missing" proteins is freely available to the
      scientific community through our web server (http://biolinfo.org/protannotator).

PMID- 24313345
TI  - Characterization of a Campylobacter fetus-like strain isolated from the faeces of
      a sick leopard tortoise (Stigmochelys pardalis) using matrix-assisted laser
      desorption/ionization time of flight as an alternative to bacterial 16S rDNA
      phylogeny.
AB  - This article describes the isolation and characterization of a Campylobacter-like
      isolate originating from the faeces of a sick leopard tortoise. Molecular as well
      as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
      characterization suggests that it could correspond to a new Campylobacter
      species. SIGNIFICANCE AND IMPACT OF THE STUDY: The major impact of this work is
      the demonstration that proteomics and especially MALDI-TOF typing can be used as
      an alternative method to 16S rDNA sequencing for phylogeny and can lead to the
      discovery of new Campylobacters.

PMID- 24313346
TI  - Inhibition of monoamine oxidase by selected phenylalkylcaffeine analogues.
AB  - OBJECTIVES: Caffeine represents a useful scaffold for the design of monoamine
      oxidase (MAO) type B inhibitors. Specifically, substitution on the C8 position
      yields structures which are high-potency MAO-B inhibitors. To explore the
      structure-activity relationships of MAO-B inhibition by caffeine-derived
      compounds, this study examines the MAO inhibitory properties of a series of
      phenylalkylcaffeine analogues. METHODS: Employing the recombinant human enzymes,
      the potencies (IC50 values) by which the caffeine analogues inhibit MAO-A and MAO
      B were measured. The reversibility of inhibition of a selected inhibitor was
      determined by measuring the recovery of enzyme activity after dilution and
      dialysis of enzyme-inhibitor mixtures. KEY FINDINGS: The results document that
      the phenylalkylcaffeine analogues are reversible and selective MAO-B inhibitors
      with a competitive mode of inhibition. The most potent analogue, 8-(7
      phenylheptyl)caffeine, exhibits IC50 values for the inhibition of MAO-A and MAO-B
      of 3.01 MUm and 0.086 MUm, respectively. Increasing the length of the alkyl side
      chain leads to enhanced MAO-A and MAO-B inhibitory potency while introduction of
      a carbonyl group reduces MAO-B inhibitory potency. CONCLUSIONS:
      Phenylalkylcaffeines represent a new class of high-potency MAO-B inhibitors with
      the longer alkyl side chains yielding enhanced inhibitory activity. Such
      compounds may represent useful leads for the development of anti-parkinsonian
      therapies.

PMID- 24313347
TI  - Morphometric comparison of clavicle outlines from 3D bone scans and 2D chest
      radiographs: a shortlisting tool to assist radiographic identification of human
      skeletons.
AB  - This paper describes a computerized clavicle identification system primarily
      designed to resolve the identities of unaccounted-for U.S. soldiers who fought in
      the Korean War. Elliptical Fourier analysis is used to quantify the clavicle
      outline shape from skeletons and postero-anterior antemortem chest radiographs to
      rank individuals in terms of metric distance. Similar to leading fingerprint
      identification systems, shortlists of the top matching candidates are extracted
      for subsequent human visual assessment. Two independent tests of the computerized
      system using 17 field-recovered skeletons and 409 chest radiographs demonstrate
      that true-positive matches are captured within the top 5% of the sample 75% of
      the time. These results are outstanding given the eroded state of some field
      recovered skeletons and the faintness of the 1950's photofluorographs. These
      methods enhance the capability to resolve several hundred cold cases for which
      little circumstantial information exists and current DNA and dental record
      technologies cannot be applied. 

PMID- 24313348
TI  - Use of illicit drugs by truck drivers arriving at Paranagua port terminal,
      Brazil.
AB  - OBJECTIVE: The purpose of this study was to estimate the prevalence of recent use
      of illicit drugs among truck drivers who had parked their vehicles at the
      terminal port in Paranagua City at Parana State, southern Brazil. METHODS: This
      cross-sectional study was part of a larger research project conducted among
      drivers at a regional Brazilian port. Data on professional characteristics,
      involvement in road traffic injuries, sleep, and use of alcohol and illicit drugs
      were collected using a questionnaire. Urine samples were collected and analyzed
      for amphetamines, cocaine, and cannabis using gas chromatography with mass
      spectrometric detection. RESULTS: Sixty-two drivers were included in the study.
      Toxicological analyses showed that 8.1 percent (95% confidence interval [CI], 2.7
      17.8%) of the urine samples were positive for drugs (4.8% for cocaine, 1.6% for
      amphetamine, and 1.6% for both); 8.1 percent reported drug use during the
      preceding 30 days in the questionnaire and only one tested positive for the drug
      in the urine sample. No sample was positive for cannabinoids. In total, at least
      14.5 percent (95% CI, 6.9-25.8%) had used illicit drugs during the preceding 30
      days based on self-reports and urine testing. Drivers who reported involvement in
      traffic injuries the year before more often tested positive for drugs in
      biological samples (P <.05). CONCLUSIONS: This research provides preliminary
      evidence that the use of illicit stimulants was common among professional truck
      drivers transporting grain loads. Thus, actions are needed to reduce drug use
      among truck drivers in order to prevent drug-related road traffic injuries.

PMID- 24313349
TI  - SHIP2: a "new" insulin pathway target for aging research.
AB  - Strong evidence suggests that systemic inflammation and central adiposity
      contribute to and perpetuate metabolic syndrome. All of these alterations
      predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular
      disease, as well as Alzheimer's disease (AD), all characterized by chronic
      inflammatory status. On the other hand, extensive abnormalities in insulin and
      insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains
      with AD have been demonstrated, suggesting that AD could be a third form of
      diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has
      an important role in the insulin pathway because its over-expression causes
      impairment of insulin/IGF-1 signaling. Because some single-nucleotide
      polymorphisms (SNP) of the gene encoding SHIP2 were significantly associated in
      T2DM patients with metabolic syndrome and some related conditions, we decided to
      conduct a case-control study on this gene, analyzing AD and T2DM subjects as
      cases and young, old, and centenarians as controls. Our results suggest a
      putative correlation between the the rs144989913 SNP and aging, both successful
      and unsuccessful, rather than age-related diseases. Because this SNP is an
      insertion/deletion of 28 bp, it might cause an alteration in SHIP2 expression. It
      is noteworthy that SHIP2 has been demonstrated to be a potent negative regulator
      of insulin signaling and insulin sensitivity. Many studies demonstrated the
      association of the insulin/IGF1 pathway with aging and longevity, so it is
      tempting to speculate that the found association with SHIP2 and aging might
      depend on its effect on the insulin/IGF-1 pathway.

PMID- 24313350
TI  - In vitro maturation of oocytes from Santa Ines ewes subjected to consecutive
      sessions of follicular aspiration by laparoscopy.
AB  - The success of embryo production in vitro depends upon the use of an efficient
      oocyte retrieval technique, and the best results have been obtained by
      laparoscopic aspiration. The aim of this study was to evaluate the effect of
      consecutive sessions of follicular aspiration on the quantity, quality and in
      vitro maturation competence of oocytes obtained from ewes subjected to hormonal
      stimulation. Six Santa Ines ewes underwent nine sessions of follicular aspiration
      by laparoscopy with a 7-day interval between sessions, totalling 56 aspirations.
      After 24 h of culture, oocytes were stained and classified according to the stage
      of nuclear and cytoplasmic maturation. Oocyte retrieval rate was 61.4 +/- 2%,
      resulting in a total of 249 oocytes. No significant variation was observed
      between sessions (p > 0.05). The average number of oocytes retrieved from each
      ewe was 6.4 +/- 2 per session and 42 +/- 4 in total. No significant difference
      was observed between the frequencies of the different stages of nuclear
      maturation: 32.72% mature, 40.74% immature and 26.54% degenerated/indeterminate
      oocytes; however, a significant difference was observed between the frequencies
      of the different stages of cytoplasmic maturation: 10.7% mature, 73.25% immature
      and 16.05% degenerated/indeterminate oocytes. No significant difference was
      observed in nuclear or cytoplasmic maturation between the weeks of procedure. We
      conclude that after nine consecutive sessions of follicular aspiration, the
      quantity and quality of retrieved oocytes remained unchanged as well as the
      levels of nuclear and cytoplasmic maturation obtained, demonstrating the
      viability of this technique for repetitive follicular aspirations on the same
      donor.

PMID- 24313351
TI  - Structural analysis of proanthocyanidins isolated from fruit stone of Chinese
      hawthorn with potent antityrosinase and antioxidant activity.
AB  - Proanthocyanidins were isolated from fruit stone of Chinese hawthorn (Crataegus
      pinnatifida Bge. var. major N.E.Br.). Their structures were analyzed and
      elucidated by methods of matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) and high performance liquid
      chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS). The
      results demonstrated that these compounds are complicated mixtures of homo- and
      heteropolymers consisting of procyanidin/procyanidin gallate and prodelphinidin.
      They possessed structural heterogeneity in monomer units, polymer length, and
      interflavan linkage (A-type and B-type). Their antityrosinase and antioxidant
      activity were then investigated. The results revealed that they can inhibit
      tyrosinase activities, including the monophenolase activity and the diphenolase
      activity. In addition, proanthocyanidins possessed potent antioxidant activity.
      Our studies revealed that proanthocyanidins isolated from fruit stone of Chinese
      hawthorn may be applied in food, agriculture, pharmaceutical, and cosmetic
      industries. 

PMID- 24313352
TI  - Performance of a commercial Chicken-Ovo-transferrin-ELISA on the serum of brown
      layer chickens infected with Gallibacterium anatis and Streptococcus
      zooepidemicus.
AB  - To evaluate Ovo-transferrin (OTF), a positive acute-phase protein in chickens, as
      a diagnostic biomarker of selected bacterial infections we checked the
      performance of a commercial Chicken-OTF-ELISA (ICL, Inc., Portland, OR, USA) by
      analytical and overlap performances using two groups of serum samples obtained
      from 26 Gallibacterium anatis-infected and 20 Streptococcus zooepidemicus
      infected brown layer chickens. In addition, sera from 14 apparently healthy and
      19 negative control chickens were analysed in the Gallibacterium group whereas
      sera from 20 healthy and 11 negative control chickens from the Streptococcus
      group were analysed. All calibration curves revealed high coefficients of
      determination (>= 0.97) between optical density (OD 450nm) and concentrations of
      OTF (mg/ml). OTF concentrations in high, medium and low pools (made of sera from
      a combination of infected and/or non-infected birds) were >6.4, >3.8 to <4.5 and
      <1.6 mg/ml in the Gallibacterium group, and >6.7, >3.5 to <3.7 and <1.1 mg/ml in
      the Streptococcus group, respectively. For each pool, low coefficients of intra
      assay (7.8, 5.7 and 5.3) and inter-assay (15.8, 18.0 and 18.0) variations were
      obtained in the Gallibacterium study. In the Streptococcus study only the intra
      assay variation was low (3.7, 3.8 and 6.2, respectively). The linearity check was
      acceptable demonstrating a straight line with slope and intercept, not deviating
      from one and zero, respectively, using the Gallibacterium sera, whereas the
      Streptococcus sera deviated from the linear line. Detection limits were low
      (Gallibacterium, 0.01 mg/ml; Streptococcus, 0.32 mg/ml). OTF concentrations (mean
      +/- standard error of the mean) in overlap performances were elevated in the sera
      of infected chickens (Gallibacterium, 4.4 +/- 0.3 mg/ml; Streptococcus, 3.2 +/-
      0.4 mg/ml) compared with negative controls (1.7 +/- 0.1 mg/ml) (P < 0.05). In
      conclusion, the Chicken-OTF-ELISA can be used to measure reproducible serum OTF
      concentrations in brown layer chickens as a response to G. anatis infections,
      whereas an adjustment of dilution process is proposed to optimize to use in S.
      zooepidemicus-infected chickens.

PMID- 24313353
TI  - Straightforward assembly of benzoxepines by means of a rhodium(III)-catalyzed C-H
      functionalization of o-vinylphenols.
AB  - Readily available o-vinylphenols undergo a formal (5 + 2) cycloaddition to
      alkynes when treated with catalytic amounts of [Cp*RhCl2]2 and Cu(OAc)2. The
      reaction, which involves the cleavage of the terminal C-H bond of the alkenyl
      moiety, generates highly valuable benzoxepine skeletons in a practical,
      versatile, and atom-economical manner. Using carbon monoxide instead of an alkyne
      as reaction partner leads to coumarin products which formally result from a (5 +
      1) cycloaddition. 

PMID- 24313354
TI  - Discontinuation of empirical antibiotic therapy in neutropenic acute myeloid
      leukaemia patients with fever of unknown origin: is it ethical?
AB  - Based on recommendations of the ECIL-4, we prospectively evaluated
      discontinuation of empirical antibiotic therapy in high-risk neutropenic acute
      myeloid leukaemia patients with fever of unknown origin. Seven patients (median
      neutropenia duration 30 days) were included. Four of them remained afebrile but
      quickly recovered from neutropenia. The other three had rapid recurrent fever.
      Two of these three patients had bacteraemia with susceptible strains and one of
      them was transferred to the ICU for septic shock. Median duration of sparing of
      antibiotics for the seven patients was 3 days (2-4). Because of these limited
      results the study was stopped.

PMID- 24313355
TI  - Evaluating the Productive Ward at an acute NHS trust: experiences and
      implications of releasing time to care.
AB  - AIMS AND OBJECTIVES: To demonstrate how a national programme aimed to increase
      the amount of direct time nurses spend with patients', impacts on both staff and
      patient experience. BACKGROUND: The Productive Ward is an improvement programme
      developed by the NHS Institute for Innovation and Improvement (2007,
      http://www.institute.nhs.uk/quality_and_value/productivity_series/productive_ward
      html) which aims to enable nurses to work more efficiently by reviewing process
      and practice, thus releasing more time to spend on direct patient care. However,
      there is little empirical published research around the programme, particularly
      concerning impact, sustainability and the patient perspective. DESIGN: This
      manuscript presents the findings from qualitative interviews involving both staff
      and patients. METHODS: Semi-structured one-to-one interviews were conducted with
      patients (n = 8) and staff (n = 5) on five case study wards. Seven focus groups
      were held according to staff grade (n = 29). RESULTS: Despite initial scepticism,
      most staff embraced the opportunity and demonstrated genuine enthusiasm and
      energy for the programme. Patients were generally complimentary about their
      experience as an inpatient, reporting that staff made them feel safe, comfortable
      and cared for. CONCLUSION: Findings showed that the aims of the programme were
      partially met. The implementation of Productive Ward was associated with
      significant changes to the ward environment and improvements for staff. The
      programme equipped staff with skills and knowledge which acted as a primer for
      subsequent interventions. However, there was a lack of evidence to demonstrate
      that Productive Ward released time for direct patient care in all areas that
      implemented the programme. RELEVANCE TO CLINICAL PRACTICE: Developing robust
      performance indicators including a system to capture reinvestment of direct care
      time would enable frontline staff to demonstrate impact of the programme.
      Additionally, staff will need to ensure that reorganisation and instability
      across the NHS do not affect sustainability and viability of the Productive Ward
      in the long term.

PMID- 24313356
TI  - A system justification view of sexual violence: legitimizing gender inequality
      and reduced moral outrage are connected to greater rape myth acceptance.
AB  - Rape is a pervasive social problem that causes serious physical and psychological
      repercussions. Rape victims' recovery is often complicated by the public's
      failure to believe the victim and restore justice. This study applied system
      justification theory to examine whether the justification of gender inequality is
      related to moral outrage (an emotional precursor to corrective action) and rape
      myth acceptance; we also examined whether rape myth acceptance is associated with
      moral outrage at injustice. Results showed that gender-specific system
      justification correlated with less moral outrage at human suffering as well as
      greater rape myth acceptance. The relationships between these variables were
      similar for men and for women, a finding that suggests that rape myths are system
      justifying for women. When we controlled for gender-specific system
      justification, rape myth acceptance correlated with less moral outrage. Results
      are discussed in the context of how legitimizing ideologies reduce moral outrage
      at injustice and perpetuate a system of sexual violence. 

PMID- 24313357
TI  - alpha-Smooth muscle actin-positive myofibroblasts, in association with epithelial
      mesenchymal transition and lymphogenesis, is a critical prognostic parameter in
      patients with oral tongue squamous cell carcinoma.
AB  - BACKGROUND: alpha-Smooth muscle actin (alpha-SMA)-positive myofibroblasts play a
      pivotal role in progression and metastasis of solid carcinomas. Epithelial
      mesenchymal transition (EMT) of cancer cells and lymphogenesis of tumor
      microenvironment are the important events in tumor metastasis. This study aimed
      to investigate the relationship between the expression of myofibroblasts marker,
      alpha-SMA, and clinicopathological features, EMT, lymphogenesis, and prognostic
      status in oral tongue squamous cell carcinoma (OTSCC). METHODS:
      Immunohistochemisty was used to detect alpha-SMA expression in 50 OTSCCs. EMT and
      lymphogenesis were also identified by immunostaining with N-cadherin, vimentin,
      and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). RESULTS: There
      was a significant correlation respectively between the alpha-SMA (P = 0.002),
      vimentin (P < 0.001), N-cadherin (P = 0.025) expression and cervical lymph node
      metastasis of OTSCC. Carcinomas with alpha-SMA (P = 0.001), vimentin (P = 0.003),
      and N-cadherin (P = 0.012) expression were more advanced in terms of tumor-node
      metastases status. Univariate analysis showed that pathologic node status (P <
      0.001), alpha-SMA (P = 0.001), and vimentin expression (P = 0.044) was
      significantly associated with overall survival time, but multivariate analysis
      just showed the alpha-SMA expression (P = 0.008) and pathologic node status (P =
      0.003) was independently predictive of prognosis. Furthermore, statistical
      analysis showed significant correlation between alpha-SMA expression and vimentin
      (P = 0.037), N-cadherin (P = 0.019), or LYVE-1 positive vessel count (P = 0.041).
      CONCLUSION: Our results indicate that alpha-SMA-positive myofibroblasts have
      important impacts on cancer progression, metastasis, and survival prognosis of
      patients with OTSCC. The functions of alpha-SMA-positive myofibroblasts in OTSCC
      may be associated with promoting EMT of tumor cells and lymphogenesis of
      metastasis microenvironment.

PMID- 24313358
TI  - Signing below the dotted line: signature position as a marker of vulnerability
      for visuospatial processing difficulties.
AB  - Almost one-third of the participants in a neuropsychological study signed the
      consent form below the given line. The relationship between a signature position
      on or below the line and participants' cognitive function was investigated. Fifty
      drug-dependent individuals, 50 of their siblings, and 50 unrelated control
      participants completed a battery of neuropsychological tests using the Cambridge
      Neuropsychological Test Automated Battery (CANTAB). Individuals signing below,
      rather than on, the line performed more poorly on tests of visuospatial memory,
      but no differently on other cognitive tests. Signature positioning may be a soft
      sign for impairment of the mechanisms involved in visuospatial memory. 

PMID- 24313359
TI  - Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis
      patients show distinct characteristics.
AB  - Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation
      of patients with rheumatoid arthritis (RA), but are less common in the rheumatic
      joint. In the present study, we sought to identify functional differences between
      CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with
      conventional CD28-expressing CD4(+) T cells. Forty-four patients with RA,
      displaying a distinct CD4(+) CD28(null) T cell population in blood, were
      recruited for this study; the methylation status of the IFNG locus was examined
      in isolated T cell subsets, and intracellular cytokine production (IFN-gamma,
      TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were
      assessed by flow cytometry on T cells from the two compartments. Circulating
      CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1
      region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced
      higher levels of both IFN-gamma and TNF after TCR cross-linking. CD4(+)
      CD28(null) T cells from the site of inflammation expressed significantly more
      CXCR3 and CCR6 compared to their counterparts in blood. While IL-17A production
      could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant
      production was observed in CD4(+) CD28(null) T cells from synovial fluid. CD4(+)
      CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+)
      T cells in the circulation, but we could also demonstrate that synovial CD4(+)
      CD28(null) T cells showed additional effector functions (IL-17 coproduction) as
      compared to the same subset in peripheral blood, suggesting an active role for
      these cells in the perpetuation of inflammation in the subset of patients having
      a CD28(null) population. 

PMID- 24313360
TI  - Radical [3 + 2]-annulation of divinylcyclopropanes: rapid synthesis of complex
      meloscine analogs.
AB  - A radical [3 + 2]-divinylcyclopropane annulation cascade has been extended to
      encompass five D-ring variants of the meloscine/epimeloscine core structure.
      Representative ABCD tetracyclic intermediates were further elaborated with novel
      substituted E-rings through subsequent transformations of advanced intermediates
      that provided opportunities for late-stage variation of the B-ring (lactam) N
      substituents which were also developed. 

PMID- 24313361
TI  - Influence on alveolar resorption of the buccal bony plate width in the edentulous
      ridge expansion (E.R.E.)--an experimental study in the dog.
AB  - OBJECTIVE: To compare the hard tissue changes at implants installed applying
      edentulous ridge expansion (E.R.E.) at sites with a buccal bony wall thickness of
      1 or 2 mm. MATERIAL AND METHODS: In six Labrador dogs, the first and second
      maxillary incisors were extracted, and the buccal alveolar bony plates and septa
      were removed. After 3 months of healing, partial-thickness flaps were dissected,
      and the E.R.E. was applied bilaterally. Hence, an expansion of the buccal bony
      crest was obtained in both sides of the maxilla with a displacement of either a 1
      or a 2-mm-wide buccal bony plate at the test and control sites, respectively.
      After 3 months of healing, biopsies were obtained for histological analyses.
      RESULTS: A buccal vertical resorption of the alveolar crest of 2.3 +/- 0.8 and
      2.1 +/- 1.1 mm, and a coronal level of osseointegration at the buccal aspect of
      2.7 +/- 0.5 and 2.9 +/- 0.9 mm were found at the test (1 mm) and control (2 mm)
      sites, respectively. The differences did not reach statistical significance. The
      mean values of the mineralized bone-to-implant contact (MBIC%) ranged from 62% to
      73% at the buccal and lingual sites. No statistically significant differences
      were found. Horizontal volume gains of 1.8 and 1.1 mm were observed at the test
      and control sites, respectively, and the difference being statistically
      significant. CONCLUSIONS: Implants installed using the E.R.E. technique yielded a
      high degree of osseointegration. It is suggested that the displacement of buccal
      bony plates of 1 mm thickness is preferable compared with that of wider
      dimensions.

PMID- 24313362
TI  - Self-catalytic growth of unmodified gold nanoparticles as conductive bridges
      mediated gap-electrical signal transduction for DNA hybridization detection.
AB  - A simple and sensitive gap-electrical biosensor based on self-catalytic growth of
      unmodified gold nanoparticles (AuNPs) as conductive bridges has been developed
      for amplifying DNA hybridization events. In this strategy, the signal
      amplification degree of such conductive bridges is closely related to the
      variation of the glucose oxidase (GOx)-like catalytic activity of AuNPs upon
      interaction with single- and double-stranded DNA (ssDNA and dsDNA), respectively.
      In the presence of target DNA, the obtained dsDNA product cannot adsorb onto the
      surface of AuNPs due to electrostatic interaction, which makes the unmodified
      AuNPs exhibit excellent GOx-like catalytic activity. Such catalytic activity can
      enlarge the diameters of AuNPs in the glucose and HAuCl4 solution and result in a
      connection between most of the AuNPs and a conductive gold film formation with a
      dramatically increased conductance. For the control sample, the catalytic
      activity sites of AuNPs are fully blocked by ssDNA due to the noncovalent
      interaction between nucleotide bases and AuNPs. Thus, the growth of the assembled
      AuNPs will not happen and the conductance between microelectrodes will be not
      changed. Under the optimal experimental conditions, the developed strategy
      exhibited a sensitive response to target DNA with a high signal-to-noise ratio.
      Moreover, this strategy was also demonstrated to provide excellent
      differentiation ability for single-nucleotide polymorphism. Such performances
      indicated the great potential of this label-free electrical strategy for clinical
      diagnostics and genetic analysis under real biological sample separation. 

PMID- 24313363
TI  - Design of a high performance thin all-solid-state supercapacitor mimicking the
      active interface of its liquid-state counterpart.
AB  - Here we report an all-solid-state supercapacitor (ASSP) which closely mimics the
      electrode-electrolyte interface of its liquid-state counterpart by impregnating
      polyaniline (PANI)-coated carbon paper with polyvinyl alcohol-H2SO4 (PVA-H2SO4)
      gel/plasticized polymer electrolyte. The well penetrated PVA-H2SO4 network along
      the porous carbon matrix essentially enhanced the electrode-electrolyte interface
      of the resulting device with a very low equivalent series resistance (ESR) of 1
      Omega/cm(2) and established an interfacial structure very similar to a liquid
      electrolyte. The designed interface of the device was confirmed by cross
      sectional elemental mapping and scanning electron microscopy (SEM) images. The
      PANI in the device displayed a specific capacitance of 647 F/g with an areal
      capacitance of 1 F/cm(2) at 0.5 A/g and a capacitance retention of 62% at 20 A/g.
      The above values are the highest among those reported for any solid-state
      supercapacitor. The whole device, including the electrolyte, shows a capacitance
      of 12 F/g with a significantly low leakage current of 16 MUA(2). Apart from this,
      the device showed excellent stability for 10000 cycles with a coulombic
      efficiency of 100%. Energy density of the PANI in the device is 14.3 Wh/kg. 

PMID- 24313364
TI  - Investigation of differences between nanosecond electropulse and electrohydraulic
      methods of lithotripsy: a comparative in vitro study of efficacy.
AB  - PURPOSE: To compare the effectiveness of novel nanosecond electropulse
      lithotripsy with standard electrohydraulic lithotripsy to demonstrate and
      authenticate their differences because both modalities appear to be similar.
      MATERIALS AND METHODS: An in vitro fragmentation study was conducted using cuboid
      BegoStone phantoms, which mimic hard and soft stones, based on an established
      model. Three different stone sizes were used in the testing having volumes of
      100, 256, and 320 mm(3). A nanosecond electropulse lithotripter (NEPL) and an
      electrohydraulic lithotripter (EHL) were operated using a range of probe sizes at
      comparable energy settings and pulse rates with the objective of obtaining a
      stone fragment <2 mm. To compare the efficacy of these two lithotripters, the
      number of pulses needed for stone phantom fragmentation was recorded according to
      probe size and energy setting, which were then converted into units of cumulative
      energy. RESULTS: The results clearly demonstrated that, for all operating modes
      and stone phantom types, the NEPL device needs much less cumulative energy and
      thus fewer pulses and consequently less time to achieve stone fragmentation than
      the EHL device. The disparity in the results is explained by the dissimilar
      mechanisms at work in the compared lithotripters during destruction of the stone.
      The electropulse stone disintegration mechanism transfers energy directly into
      the stone because of discharge penetration into a solid body. This contrasts with
      the electrohydraulic mechanism in EHL in which energy is transferred through the
      liquid medium, which also creates a damaging shockwave. CONCLUSIONS: The findings
      demonstrate that, for all operating modes and stone types, the NEPL device needs
      much less cumulative energy and thus fewer pulses for stone fragmentation than
      the EHL device. The disparity in the results is explained by the dissimilar
      mechanisms at work in the compared lithotripters during destruction of the stone.

PMID- 24313365
TI  - Quick-response magnetic nanospheres for rapid, efficient capture and sensitive
      detection of circulating tumor cells.
AB  - The study on circulating tumor cells (CTCs) has great significance for cancer
      prognosis, treatment monitoring, and metastasis diagnosis, in which isolation and
      enrichment of CTCs are key steps due to their extremely low concentration in
      peripheral blood. Herein, magnetic nanospheres (MNs) were fabricated by a
      convenient and highly controllable layer-by-layer assembly method. The MNs were
      nanosized with fast magnetic response, and nearly all of the MNs could be
      captured by 1 min attraction with a commercial magnetic scaffold. In addition,
      the MNs were very stable without aggregation or precipitation in whole blood and
      could be re-collected nearly at 100% in a monodisperse state. Modified with anti
      epithelial-cell-adhesion-molecule (EpCAM) antibody, the obtained immunomagnetic
      nanospheres (IMNs) successfully captured extremely rare tumor cells in whole
      blood with an efficiency of more than 94% via only a 5 min incubation. Moreover,
      the isolated cells remained viable at 90.5 +/- 1.2%, and they could be directly
      used for culture, reverse transcription-polymerase chain reaction (RT-PCR), and
      immunocytochemistry (ICC) identification. ICC identification and enumeration of
      the tumor cells in the same blood samples showed high sensitivity and good
      reproducibility. Furthermore, the IMNs were successfully applied to the isolation
      and detection of CTCs in cancer patient peripheral blood samples, and even one
      CTC in the whole blood sample was able to be detected, which suggested they would
      be a promising tool for CTC enrichment and detection. 

PMID- 24313366
TI  - Quantification of perspective-induced shape change of clavicles at radiography
      and 3D scanning to assist human identification.
AB  - Change in perspective between antemortem and postmortem imaging sessions
      (radiograph to radiograph and surface scan to radiograph) may cause different 2D
      renderings of the same osseous element complicating comparisons for
      identification. In this study, clavicle shape changes due to radiographic
      positioning and 3D laser scanning were examined in 20 right-side specimens, as
      pertinent to chest radiograph comparisons. Results indicate substantial changes
      in clavicle form with short source-to-image receptor distance, elevation of the
      element from the image receptor, and movement of the element away from the center
      beam (10% mean square for shape). Although quantitative shape differences were
      small when the clavicle was in close opposition to the image receptor (3% mean
      square), important qualitative differences remained with large distances from the
      center beam (e.g., conoid tubercle presence/absence). The significance of these
      results for image superimposition and computer-automated-shape-based searches of
      radiographic libraries to find matching candidates is discussed. 

PMID- 24313367
TI  - Happy birthday, Hans Faust: 85!

PMID- 24313368
TI  - Nitrate turnover in a peat soil under drained and rewetted conditions: results
      from a [(15)N]nitrate-bromide double-tracer study.
AB  - Under natural conditions, peatlands are generally nitrate-limited. However,
      recent concerns about an additional N input into peatlands by atmospheric N
      deposition have highlighted the risk of an increased denitrification activity and
      hence the likelihood of a rise of emissions of the greenhouse gas nitrous oxide.
      Therefore, the aim of the present study was to investigate the turnover of added
      nitrate in a drained and a rewetted peatland using a [(15)N]nitrate-bromide
      double-tracer method. The double-tracer method allows a separation between
      physical effects (dilution, dispersion and dislocation) and microbial and
      chemical nitrate transformation by comparing with the conservative Br(-) tracer.
      In the drained peat site, low NO3(-) consumption rates have been observed. In
      contrast, NO3(-) consumption at the rewetted peat site rises rapidly to about
      100% within 4 days after tracer application. Concomitantly, the (15)N abundances
      of nitrite and ammonium in soil water increased and lead to the conclusion that,
      besides commonly known NO3(-) reduction to nitrite (i.e. denitrification), a
      dissimilatory nitrate reduction to ammonium has simultaneously taken place. The
      present study reveals that increasing NO3(-) inputs into rewetted peatlands via
      atmospheric deposition results in a rapid NO3(-) consumption, which could lead to
      an increase in N2O emissions into the atmosphere. 

PMID- 24313369
TI  - Selected articles of the 3rd Joint European Stable Isotope User Meeting (JESIUM),
      Leipzig, Germany, 2-7 September 2012.

PMID- 24313370
TI  - Isotope-labelled urea to test colon drug delivery devices in vivo: principles,
      calculations and interpretations.
AB  - This paper describes various methodological aspects that were encountered during
      the development of a system to monitor the in vivo behaviour of a newly developed
      colon delivery device that enables oral drug treatment of inflammatory bowel
      diseases. [(13)C]urea was chosen as the marker substance. Release of [(13)C]urea
      in the ileocolonic region is proven by the exhalation of (13)CO2 in breath due to
      bacterial fermentation of [(13)C]urea. The (13)CO2 exhalation kinetics allows the
      calculation of a lag time as marker for delay of release, a pulse time as marker
      for the speed of drug release and the fraction of the dose that is fermented. To
      determine the total bioavailability, also the fraction of the dose absorbed from
      the intestine must be quantified. Initially, this was done by calculating the
      time-dependent [(13)C]urea appearance in the body urea pool via measurement of
      (13)C abundance and concentration of plasma urea. Thereafter, a new methodology
      was successfully developed to obtain the bioavailability data by measurement of
      the urinary excretion rate of [(13)C]urea. These techniques required two
      experimental days, one to test the coated device, another to test the uncoated
      device to obtain reference values for the situation that 100 % of [(13)C]urea is
      absorbed. This is hampered by large day-to-day variations in urea metabolism.
      Finally, a completely non-invasive, one-day test was worked out based on a dual
      isotope approach applying a simultaneous administration of [(13)C]urea in a
      coated device and [(15)N2]urea in an uncoated device. All aspects of isotope
      related analytical methodologies and required calculation and correction systems
      are described. 

PMID- 24313371
TI  - A novel methodological approach for delta(18)O analysis of sugars using gas
      chromatography-pyrolysis-isotope ratio mass spectrometry.
AB  - Although the instrumental coupling of gas chromatography-pyrolysis-isotope ratio
      mass spectrometry (GC-Py-IRMS) for compound-specific delta(18)O analysis has been
      commercially available for more than a decade, this method has been hardly
      applied so far. Here we present the first GC-Py-IRMS delta(18)O results for
      trimethylsilyl-derivatives of plant sap-relevant sugars and a polyalcohol
      (glucose, fructose, sucrose, raffinose and pinitol). Particularly, we focus on
      sucrose, which is assimilated in leaves and which is the most important transport
      sugar in plants and hence of utmost relevance in plant physiology and
      paleoclimate studies. Replication measurements of sucrose standards and
      concentration series indicate that the GC-Py-IRMS delta(18)O measurements are not
      stable over time and that they are amount (area) dependent. We, therefore,
      suggest running sample batch replication measurements in alternation with
      standard concentration series of reference material. This allows for carrying out
      (i) a drift correction, (ii) a calibration against reference material and (iii)
      an amount (area) correction. Tests with (18)O-enriched water do not provide any
      evidence for oxygen isotope exchange reactions affecting sucrose and raffinose.
      We present the first application of GC-Py-IRMS delta(18)O analysis for sucrose
      from needle extract (soluble carbohydrate) samples. The obtained
      delta(18)Osucrose/ Vienna Standard Mean Ocean Water (VSMOW) values are more
      positive and vary in a wider range (32.1-40.1 0/00) than the delta(18)Obulk/
      VSMOW values (24.6-27.2 0/00). Furthermore, they are shown to depend on the
      climate parameters maximum day temperature, relative air humidity and cloud
      cover. These findings suggest that delta(18)Osucrose of the investigated needles
      very sensitively reflects the climatically controlled evaporative (18)O
      enrichment of leaf water and thus highlights the great potential of GC-Py-IRMS
      delta(18)Osucrose analysis for plant physiology and paleoclimate studies. 

PMID- 24313372
TI  - Analysis of the coexisting pathways for NO and N2O formation in Chernozem using
      the (15)N-tracer SimKIM-Advanced model.
AB  - The nitrogen (N) cycle consists of a variety of microbial processes. These
      processes often occur simultaneously in soils, but respond differently to local
      environmental conditions due to process-specific biochemical restrictions (e.g.
      oxygen levels). Hence, soil nitrogen cycling (e.g. soil N gas production through
      nitrification and denitrification) is individually affected through these
      processes, resulting in the complex and highly dynamic behaviour of total soil N
      turnover. The development and application of methods that facilitate the
      quantification of individual contributions of coexisting processes is a
      fundamental prerequisite for (i) understanding the dynamics of soil N turnover
      and (ii) implementing these processes in ecosystem models. To explain the
      unexpected results of the triplet tracer experiment (TTE) of Russow et al. (Role
      of nitrite and nitric oxide in the processes of nitrification and denitrification
      in soil: results from (15)N tracer experiments. Soil Biol Biochem. 2009;41:785
      795) the existing SimKIM model was extended to the SimKIM-Advanced model through
      the addition of three separate nitrite subpools associated with ammonia
      oxidation, oxidation of organic nitrogen (Norg), and denitrification,
      respectively. For the TTE, individual treatments with (15)N ammonium, (15)N
      nitrate, and (15)N nitrite were conducted under oxic, hypoxic, and anoxic
      conditions, respectively, to clarify the role of nitric oxide as a
      denitrification intermediate during N2O formation. Using a split nitrite pool,
      this analysis model explains the observed differences in the (15)N enrichments in
      nitric oxide (NO) and nitrous oxide (N2O) which occurred in dependence on
      different oxygen concentrations. The change from oxic over hypoxic to anoxic
      conditions only marginally increased the NO and N2O release rates (1.3-fold). The
      analysis using the model revealed that, under oxic and hypoxic conditions, Norg
      based N2O production was the dominant pathway, contributing to 90 and 50 % of the
      total soil N2O release. Under anoxic conditions, denitrification was the dominant
      process for soil N2O release. The relative contribution of Norg to the total soil
      NO release was small. Ammonia oxidation served as the major pathway of soil NO
      release under oxic and hypoxic conditions, while denitrification was dominant
      under anoxic conditions. The model parameters for soil with moderate soil organic
      matter (SOM) content were not scalable to an additional data set for soil with
      higher SOM content, indicating a strong influence of SOM content on microbial N
      turnover. Thus, parameter estimation had to be re-calculated for these
      conditions, highlighting the necessity of individual soil-dependent parameter
      estimations. 

PMID- 24313373
TI  - N(2)O emissions and source processes in snow-covered soils in the Swiss Alps.
AB  - Nitrous oxide (N2O) emissions from snow-covered soils represent a significant
      fraction of the annual flux from alpine, subalpine or cold-temperate regions. In
      winter 2010-2011, we investigated the temporal variability of N2O emissions and
      source processes from a subalpine valley in the Swiss Alps. The study included
      regular measurements of N2O snow profiles at a fixed location and an intensive
      sampling campaign along a transversal cut through the valley with grassland at
      the bottom and coniferous forest at the slopes. During the intensive campaign,
      recently developed laser spectroscopy was employed for high-precision N2O
      isotopomer analysis. Maximum N2O fluxes (0.77+/-0.64 nmol m(-2) h(-1)) were found
      for periods with elevated air temperature and, in contrast to our expectations,
      were higher from forest than from grassland in mid-February. At maximum snow
      height (63 cm) the main N2O source processes were heterotrophic denitrification
      and nitrifier denitrification. The reduction of N2O by heterotrophic denitrifiers
      was much more pronounced for the grassland compared with the forest soil, as
      indicated by the (15)N site preferences of 16.4+/-11.5 0/00 (grassland) and-1.6+/
      2.1 0/00 (forest). This illustrates the potential of laser spectroscopic N2O
      isotopomer analysis for the identification of source processes even at low
      emission rates in nutrient poor ecosystems. 

PMID- 24313374
TI  - Stable carbon isotopes of glucose received from pine tree-rings as bioindicators
      of local industrial emission of CO2 in Niepolomice Forest (1950-2000).
AB  - The mass spectrometric investigations of carbon isotope composition of glucose
      received from alpha-cellulose samples derived from Scots pine (Pinus sylvestris
      L.) growing in Niepolomice Forest were the main aim of this study. The annual
      rings covered the time span from 1950 to 2000. alpha-Cellulose samples were
      extracted from increment cores of four representative trees, and then acid
      hydrolysis was performed. The number of sunshine hours, thermal and pluvial
      conditions of the growing season and in the preceding months had a significant
      effect on pine. Also non-climatic factors, most likely by industrial pollution
      signal, have been recorded in the isotopic composition of glucose. The
      relationship between climatic conditions, carbon dioxide emission and annual tree
      rings carbon isotopic composition was analysed, using methods of correlation and
      response function, and multiple regression function. 

PMID- 24313375
TI  - Stable isotopes in river waters in the Tajik Pamirs: regional and temporal
      characteristics.
AB  - The Gunt River catchment in the Central Pamirs is a representative of the
      headwater catchments of the Aral Sea Basin. It covers 14,000 km(2), spanning
      altitudes between 2000 and 6700 m a.s.l. In a monitoring network, water samples
      were taken at 30 sampling points every month and analysed for the stable water
      isotopes ((18)O and (2)H). Our first results show delta(2)H values in the range
      from-131.2 to-94.9 0/00 and delta(18)O values from-18.0 to-14.0 0/00. The stable
      isotope patterns in the catchment seem to follow a systematic way, dominated by
      an altitude effect with a mean Delta delta(2)H=-3.6 0/00/100 m. The observed
      seasonal variations can be explained by geographical aspects such as the
      influence of different wind systems as well as melting processes. 

PMID- 24313376
TI  - Obituary for Dr Peter Werle.

PMID- 24313378
TI  - Quantification of ErbB network proteins in three cell types using complementary
      approaches identifies cell-general and cell-type-specific signaling proteins.
AB  - Relating protein concentration to cell-type-specific responses is one of the
      remaining challenges for obtaining a quantitative systems level understanding of
      mammalian signaling. Here we used mass-spectrometry (MS)- and antibody-based
      quantitative proteomic approaches to measure protein abundances for 75% of a hand
      curated reconstructed ErbB network of 198 proteins, in two established cell types
      (HEK293 and MCF-7) and in primary keratinocyte cells. Comparison with other
      quantitative studies allowed building a set of ErbB network proteins expressed in
      all cells and another which are cell-specific and could impart specific
      properties to the network. As a proof-of-concept of the importance of protein
      concentration, we generated a small simplified mathematical model encompassing
      ligand binding, followed by receptor dimerization, activation, and degradation.
      The model predicts ErbB phosphorylation in HEK293, MCF-7, and keratinocyte cells
      simply by incorporating cell-type-specific ErbB1, ErbB2, and caveolin-1
      abundances but otherwise contains similar rate constants. Altogether, the data
      provide a resource for protein abundances and localization to be included in
      larger mathematical models, enabling the generation of cell-type-specific
      computational models. MS data have been deposited to the ProteomeXchange via
      PRIDE (with identifier PXD000623) and PASSEL (with identifier PASS00372). 

PMID- 24313379
TI  - South African mothers' coping with an unplanned Caesarean section.
AB  - In this study, researchers explored mothers' coping strategies in dealing with
      birth by unplanned Caesarean section. Mothers' experiences of a traumatic birth
      could be influenced by perceived strengths when coping with the stress related to
      the incident. Coping strategies resulted in reassessment of the birth process and
      were associated with a more positive and memorable experience. In-depth
      interviews with 10 women explored their lived experiences of childbirth. Data
      were analyzed thematically. Phenomenological theory served as a framework for the
      structuring, organizing, and categorizing of data. Mothers described several
      factors and coping strategies that they perceived to be effective in reducing the
      impact of their traumatic birth experiences. 

PMID- 24313381
TI  - Identification of volatile markers in potato brown rot and ring rot by combined
      GC-MS and PTR-MS techniques: study on in vitro and in vivo samples.
AB  - Ralstonia solanacearum (Rs) and Clavibacter michiganensis subsp. sepedonicus
      (Cms) are the bacterial causal agents of potato brown and ring rot, respectively,
      and are included in the A2 list of quarantine pathogens in Europe. Identification
      by GC-MS analysis of volatile organic compounds from Rs or Cms cultured on
      different nutrient media was performed. GC-MS and PTR-MS analysis were carried
      out also on unwounded potato tubers infected with the same pathogens. Infected
      tubers were produced by experimental inoculations of the plants. In in vitro
      experiments, Rs or Cms emitted volatile compounds, part of which were specific
      disease markers of potato (2-propanol and 3-methylbutanoic acid), mainly
      originating from bacterial metabolism (i.e., amino acid degradation, carbohydrate
      and fatty acid oxidation). In potato tubers, pathogen metabolism modified the
      volatile compound pattern emitted from healthy samples. Both bacteria seem to
      accelerate metabolic processes ongoing in potatoes and, in the case of Rs,
      disease markers (1-hepten-3-ol, 3,6-dimethyl-3-octanone, 3-ethyl-3-methylpentane,
      1-chloroctane, and benzothiazole) were identified. 

PMID- 24313382
TI  - Primary systemic vasculitis with severe alpha1-antitrypsin deficiency revisited.
AB  - OBJECTIVES: To study the clinical characteristics and epidemiology of the
      combination of primary systemic vasculitis (PSV) and severe alpha-1 antitrypsin
      (alpha1-AT) deficiency. METHOD: Patients with PSV [granulomatosis with
      polyangiitis (GPA) (Wegener's), microscopic polyangiitis, eosinophilic
      granulomatosis with polyangiitis (EGPA) (Churg-Strauss), and polyarteritis
      nodosa] were identified through diagnosis registries and serological databases.
      Clinical and laboratory data, including the presence of severe alpha1-AT
      deficiency, were collected from the time of diagnosis. During follow-up, data on
      relapses and permanent organ damage were collected. Using the county of Skane as
      the denominator population, we estimated the annual incidence rate and point
      prevalence of PSV in people with severe alpha1-AT deficiency. RESULTS: Five
      patients (three women, median age 49 years) with PSV diagnosed between 1996 and
      2008 were found to have alpha1-AT deficiency, all of them carrying the protease
      inhibitor ZZ (PiZZ) phenotype. During follow-up (median time 166 months, range 53
      208), four patients experienced a total of 13 relapses. The median Vasculitis
      Damage Index (VDI) score for all patients was 3 (range 1-4) at year 1, and 7
      (range 3-9) at the last follow-up. The incidence rate of PSV among PiZZ carriers
      was estimated to be 397/million [95% confidence interval (CI) 8-787]. The point
      prevalence on 1 January 2013 was estimated to be 4689/million (95% CI 94-9285).
      CONCLUSIONS: In this study both the incidence and prevalence of PSV were elevated
      nearly 10-fold for individuals with severe alpha1-AT deficiency compared with the
      general population. Combined with previous publications, this indicates a dose
      response relationship for the genetic risk and suggests a causal relationship
      between the PiZ allele and vasculitis.

PMID- 24313380
TI  - A Francisella virulence factor catalyses an essential reaction of biotin
      synthesis.
AB  - We recently identified a gene (FTN_0818) required for Francisella virulence that
      seemed likely involved in biotin metabolism. However, the molecular function of
      this virulence determinant was unclear. Here we show that this protein named BioJ
      is the enzyme of the biotin biosynthesis pathway that determines the chain length
      of the biotin valeryl side-chain. Expression of bioJ allows growth of an
      Escherichia coli bioH strain on biotin-free medium, indicating functional
      equivalence of BioJ to the paradigm pimeloyl-ACP methyl ester carboxyl-esterase,
      BioH. BioJ was purified to homogeneity, shown to be monomeric and capable of
      hydrolysis of its physiological substrate methyl pimeloyl-ACP to pimeloyl-ACP,
      the precursor required to begin formation of the fused heterocyclic rings of
      biotin. Phylogenetic analyses confirmed that distinct from BioH, BioJ represents
      a novel subclade of the alpha/beta-hydrolase family. Structure-guided mapping
      combined with site-directed mutagenesis revealed that the BioJ catalytic triad
      consists of Ser151, Asp248 and His278, all of which are essential for activity
      and virulence. The biotin synthesis pathway was reconstituted reaction in vitro
      and the physiological role of BioJ directly assayed. To the best of our
      knowledge, these data represent further evidence linking biotin synthesis to
      bacterial virulence. 

PMID- 24313383
TI  - A prospective surveillance of ruptured uterus in a rural tertiary health facility
      in northwest Nigeria.
AB  - OBJECTIVE: To determine the frequency, cause and management outcome of ruptured
      uterus at a rural tertiary hospital. METHODS: Cross sectional study which
      utilized a prospective surveillance of all cases of ruptured uterus that
      presented to the hospital from 1 April 2010 to 31 March 2013. RESULTS: Frequency:
      Over the study period there were 3001 deliveries and 44 cases of ruptured uterus;
      however, three died before surgery and 41 cases had exploratory laparatomy giving
      a prevalence of 14.7/1000 deliveries or 1 in 68 deliveries. Their ages ranged
      from 18 to 45 with a mean of 28.3 +/- 6.6 years and parity varied between 1 and
      13 with majority (62.7%) being grand multiparous. Twenty-five (61.0%) lived over
      50 km away from the hospital. Causes: Prolonged/obstructed labour accounted for
      33 (80.5%) cases, 23 (56.1%) had previous caesarean sections, while injudicious
      use of oxytocin was observed in 17 (41.5%). Management outcome: All the women who
      had surgery survived but 16 (39.0%) had anaemia, 10 (24.4%) had wound infection,
      three (7.3%) developed burst abdomen and 11 (26.8%) had prolonged hospital stay.
      There were 40 (97.5%) stillbirths of which 25 (61.0%) were fresh. CONCLUSION: The
      prevalence of ruptured uterus is high especially among women with
      prolonged/obstructed labour and previous caesarean section with associated high
      perinatal mortality.

PMID- 24313384
TI  - Passive transfer of tumour-derived MDSCs inhibits asthma-related airway
      inflammation.
AB  - Myeloid-derived suppressor cells (MDSCs), a heterogeneous population including
      myeloid progenitor and immature myeloid cells, are known to inhibit T cell
      responses. The issue of whether tumour-derived MDSCs regulate the immune response
      in an asthma environment is currently unclear. Here, we have reported that tumour
      derived MDSCs shift the balance back to normal in a Th2-dominant asthmatic
      environment. In an ovalbumin (OVA)-induced mouse asthma model, injected tumour
      derived MDSCs were recruited to the lungs of asthmatic mice by CC chemokine
      ligand 2 (CCL2). MDSCs transferred into asthmatic mice via i.v. injection
      suppressed the infiltration of inflammatory cells into the lung, the Th2
      cytokine, IL-4, concentration in bronchial lavage fluid and the serum level of
      OVA-specific IgE. Increased TGF-beta1 production in the lung was detected after
      transfer of MDSCs. The inhibitory effects of MDSCs were reversed upon treatment
      with an anti-TGF-beta1 antibody, suggesting dependence of these activities on TGF
      beta1. Our findings imply that tumour-derived MDSCs inhibit the Th2 cell-mediated
      response against allergen in a TGF-beta1-dependent manner. Based on the
      collective results, we propose that asthma may be effectively targeted using a
      novel MDSC-based cell therapy approach. 

PMID- 24313385
TI  - Near-visible light and UV photoprotection in the treatment of melasma: a double
      blind randomized trial.
AB  - BACKGROUND: Melasma is an acquired hyperpigmentation on sun-exposed areas.
      Multiple approaches are used to treat it, but all include broad ultraviolet (UV)
      spectrum sunscreens. Visible light (VL) can induce pigmentary changes similar to
      those caused by UV radiation on darker-skinned patients. OBJECTIVE: To assess the
      efficacy of sunscreen with broad-spectrum UV protection that contains iron oxide
      as a VL-absorbing pigment (UV-VL) compared with a regular UV-only broad-spectrum
      sunscreen for melasma patients exposed to intense solar conditions. METHODS:
      Sixty-eight patients with melasma were randomized in two groups to receive either
      UV-VL sunscreen or UV-only sunscreen, both with sun protection factor >= 50, over
      8 weeks. All patients received 4% hydroquinone as a depigmenting treatment. At
      onset and at conclusion of the study, they were assessed by the Melasma Activity
      and Severity Index (MASI; a subjective scale), colorimetry (L*) and histological
      analysis of melanin. RESULTS: Sixty-one patients concluded the study. At 8 weeks,
      the UV-VL group showed 15%, 28% and 4% greater improvements than the UV-only
      group in MASI scores, colorimetric values and melanin assessments, respectively.
      CONCLUSIONS: UV-VL sunscreen enhances the depigmenting efficacy of hydroquinone
      compared with UV-only sunscreen in treatment of melasma. These findings suggest a
      role for VL in melasma pathogenesis.

PMID- 24313387
TI  - Swedish translation and validation of a web-based questionnaire for registration
      of overuse problems.
AB  - The main aim of this study was to translate the Oslo Sport Trauma Research Center
      (OSTRC) Overuse Injury Questionnaire into Swedish. The validity and applicability
      of the questionnaire for studying overuse injuries among Swedish handball,
      volleyball, tennis, and orienteering top athletes were also examined. The back
      translation method was used for translation. An expert committee further
      developed it for use in a study of injuries in handball, orienteering, tennis,
      and volleyball. A 10-week pretest was then conducted on 43 athletes, average age
      21 (18-31) from these sports, during which time the athletes completed the
      modified OSTRC questionnaire on a weekly basis. In the 10th week, four additional
      questions were added in order to examine the questionnaire's content validity. No
      major disagreement was found in the translation. The athletes perceived the web
      based questionnaire to be smooth and easy to complete, accurately capturing
      overuse injuries. However, suggestions were made to add questions relating to the
      hip for orienteerers and to the hand/fingers for handball players. The average
      prevalence of overuse injuries for all athletes, in any anatomical area was 22%
      (95% confidence interval 20-25). Construct validity appeared to be high, and we
      therefore suggest that the questionnaire may be used when studying overuse
      injuries in different sports. 

PMID- 24313388
TI  - Caring for the mental illness patient in emergency departments--an exploration of
      the issues from a healthcare provider perspective.
AB  - AIMS AND OBJECTIVES: To identify issues, from the emergency department
      clinicians' viewpoint, with the management of patients presenting to the
      emergency department with a mental illness. BACKGROUND: Despite the introduction
      of several statewide and national initiatives, barriers remain affecting the care
      and management of consumers presenting with an mental illness to the emergency
      department. Improving the responsiveness of mental health services, including the
      provision of more efficient emergency responses for people in crisis, is a key
      goal. To achieve responsive mental health services in emergency departments,
      services are required to work together to ensure appropriate referrals between
      mainstream services and to those services developed to meet the unique needs of
      specific population groups. DESIGN: A mixed method approach using surveys and
      focus groups. METHODS: Data were collected from patients with mental illness and
      their next of kin/carers, as well as staff working within the emergency
      department and the mental health services of the healthcare network. RESULTS: The
      study found that there were inconsistencies and deficits in the educational
      preparation of emergency department staff to manage consumers presenting with
      mental illness. Further, the inadequate physical environment of the emergency
      department contributed to difficulties in assessing and managing this group of
      patients. CONCLUSIONS: Staff members working within mental health services and
      the emergency department summarised the key improvement areas as the need for
      electronic case notes, improvements to the emergency department environment,
      mental health training, implementation of a referral service and increasing the
      number of staff. RELEVANCE TO CLINICAL PRACTICE: Although initiatives have been
      implemented, there needs to be a greater focus on educating the staff in
      emergency departments in relation to the policies and strategies which aim to
      improve the care and management of patients presenting with a mental health
      problem.

PMID- 24313389
TI  - Assessment of residual setup errors for anatomical sub-structures in image-guided
      head-and-neck cancer radiotherapy.
AB  - BACKGROUND: To quantify residual setup errors (RSE) and required planning target
      volumes (PTV) margins in head-and-neck cancer (HNC) radiotherapy when using daily
      image guidance (IG) and less-than-daily IG protocols. MATERIAL AND METHODS: Daily
      on-line kV-image registrations of 80 HNC patients (2640 imaged treatment
      fractions) were retrospectively studied to analyze RSE. Less-than-daily imaging
      protocols, using different action levels, were simulated on the data. To quantify
      local RSE; single rigid bony structures were defined as landmarks. The RSEs and
      required PTV margins were computed for each sub-structure with and without daily
      IG. RESULTS: For less-than-daily IG protocols the setup accuracy was more
      dependent on frequent imaging throughout the treatment course than the number of
      initially imaged fractions. With daily IG the RSE of the sub-structures ranged
      from 0.6 mm to 2.3 mm (systematic) and from 1.0 mm to 1.7 mm (random). Required
      PTV margins for the sub-regions ranged from 4.5 mm to 9.3 mm with no IG and from
      2.3 mm to 6.8 mm with daily IG. CONCLUSION: Anatomical changes over the treatment
      course require frequent IG to achieve accurate dose delivery using highly
      conformal radiotherapy techniques. The current study shows that considerable
      local RSE may remain even with daily IGRT. The comprehension of local RSEs in HNC
      radiotherapy is important when designating PTV margins as well as tolerance
      levels for couch correction and plan adaption.

PMID- 24313390
TI  - Perinatal characteristics and bone cancer risk in offspring--a Scandinavian
      population-based study.
AB  - BACKGROUND: We investigated perinatal factors in relation to bone cancer
      subtypes, osteosarcoma (OS), Ewing Sarcoma (ES) and chondrosarcoma (CS).
      MATERIALS AND METHODS: All cases in Norway (1970-2009), Sweden (1974-2009) and
      Denmark (1980-2010)<43 years were included (n=914); 10 controls per case were
      selected from birth registries (which provided information on pregnancies)
      matched on birth country, sex and birth year (n=9140). Unconditional logistic
      regression models including sex and birth year were used to compute relative risk
      (RR) and 95% confidence intervals (CI). RESULTS: Higher maternal education was
      associated with a 40% increase in OS risk (95% CI 1-93%). The RR for OS was 3.22
      (95% CI 1.37-7.59) comparing offspring of hypertensive mothers with those of
      mothers with a normotensive pregnancy, and Cesarean section was associated with a
      29% risk reduction (95% CI 0-50%). When gestational age, birth weight and birth
      length were assessed simultaneously, there were no associations with any of the
      bone tumor subtypes. CONCLUSION: These results provided little evidence of an
      important role of pregnancy factors in the etiology of bone cancers. Higher
      maternal education may be associated with factors, possibly early nutrition or
      other correlates of socioeconomic status, that increase OS risk in offspring. The
      elevated OS risk associated with gestational hypertension and reduced risk
      associated with Cesarean section warrant replication.

PMID- 24313391
TI  - Risk-adapted strategy partial liver irradiation for the treatment of large volume
      metastatic liver disease.

PMID- 24313392
TI  - Osteonecrosis requiring total joint arthroplasty is a rare sequel in children and
      young adults treated for solid tumors.
AB  - BACKGROUND: Osteonecrosis (ON) is a potential sequel in patients treated for
      malignancies. The goal of this population-based register study was to determine
      the incidence of ON requiring total joint arthroplasty (TJA) in patients treated
      for solid tumors in childhood, adolescence, or early adulthood. MATERIAL AND
      METHODS: Patients diagnosed with a solid tumor before the age of 31 years were
      identified from the Finnish and Danish Cancer Registries. Patients with non
      melanoma skin cancers and bone and connective tissue cancers were excluded. The
      data were combined with data from the National Hospital Discharge Registers and
      the Finnish Arthroplasty Registry. Data on the orthopedic procedures performed
      and the diagnosis codes given before the age of 40 years were retrieved. RESULTS:
      Twenty-five of 18 542 (0.13%) patients had undergone TJA. The overall 20-year
      cumulative incidence of ON requiring TJA was 1% in patients treated for kidney
      cancer, followed by 0.5% in patients with breast cancer and 0.2% in patients with
      testicular cancer. CONCLUSION: Severe ON requiring TJA is a rare sequel in
      children and young adults treated for solid tumors. It was observed most commonly
      in patients treated for renal, breast, or testicular cancer.

PMID- 24313394
TI  - Resveratrol and piceid metabolites and their fat-reduction effects in zebrafish
      larvae.
AB  - Resveratrol, a polyphenolic phytoalexin found in many plants, has been reported
      to have antiobesogenic effects in several animal and in vitro models. Zebrafish
      present several technical advantages that place them at an interesting, halfway
      point between in vitro and rodent models. The aim of the present work was to
      evaluate the metabolization of resveratrol and its glucoside (piceid) in
      zebrafish and their ability to induce the consumption of fat reserve in zebrafish
      larvae. Resveratrol and piceid were both able to reduce yolk sac fat content
      depending on the dose tested. Furthermore, resveratrol showed a potent and rapid
      action, whereas piceid needed more time and higher doses to be as effective as
      resveratrol. In accordance with other animal models and humans, the principal
      metabolites found in zebrafish larvae were monoglucoronide and monosulfate forms
      of resveratrol. In conclusion, zebrafish are a potentially excellent animal model
      for polyphenol research as they present several advantageous characteristics for
      efficacy screening and metabolomic studies before rodents.

PMID- 24313393
TI  - Genetically encoded sender-receiver system in 3D mammalian cell culture.
AB  - Engineering spatial patterning in mammalian cells, employing entirely genetically
      encoded components, requires solving several problems. These include how to code
      secreted activator or inhibitor molecules and how to send concentration-dependent
      signals to neighboring cells, to control gene expression. The Madin-Darby Canine
      Kidney (MDCK) cell line is a potential engineering scaffold as it forms hollow
      spheres (cysts) in 3D culture and tubulates in response to extracellular
      hepatocyte growth factor (HGF). We first aimed to graft a synthetic patterning
      system onto single developing MDCK cysts. We therefore developed a new localized
      transfection method to engineer distinct sender and receiver regions. A stable
      reporter line enabled reversible EGFP activation by HGF and modulation by a
      secreted repressor (a truncated HGF variant, NK4). By expanding the scale to wide
      fields of cysts, we generated morphogen diffusion gradients, controlling reporter
      gene expression. Together, these components provide a toolkit for engineering
      cell-cell communication networks in 3D cell culture. 

PMID- 24313395
TI  - 4D cryo-electron microscopy of proteins.
AB  - Cryo-electron microscopy is a form of transmission electron microscopy that has
      been used to determine the 3D structure of biological specimens in the hydrated
      state and with high resolution. We report the development of 4D cryo-electron
      microscopy by integrating the fourth dimension, time, into this powerful
      technique. From time-resolved diffraction of amyloid fibrils in a thin layer of
      vitrified water at cryogenic temperatures, we were able to detect picometer
      movements of protein molecules on a nanosecond time scale. Potential future
      applications of 4D cryo-electron microscopy are numerous, and some are discussed
      here. 

PMID- 24313396
TI  - Neurodevelopmental therapy - a popular approach.

PMID- 24313398
TI  - Time for us to work together.

PMID- 24313397
TI  - Special reactive oxygen species generation by a highly photostable BODIPY-based
      photosensitizer for selective photodynamic therapy.
AB  - We introduce a new class of photostable, efficient photosensitizers based on
      boron-dipyrromethene (BODIPY) derivatives that can generate singlet oxygen and
      super oxide simultaneously under irradiation. For compound preparation,
      appropriate regulation of the reaction conditions and control of specifically
      substituted BODIPY derivatives have been achieved. After biologically evaluating
      the intracellular uptake, localization, and phototoxicity of the compounds, we
      conclude that 3,5-dianiline-substituted BODIPY is a potentially selective
      photodynamic therapy candidate because its photodamage is more efficient in
      cancer cells than in normal cells, without apparent dark toxicity. Furthermore,
      direct comparison of photodamage efficacy revealed that our compound has better
      efficacy than Foscan and nearly equal efficacy to that of methylene blue. 

PMID- 24313406
TI  - Keogh report may be 'hard sell' to politicians and public.

PMID- 24313407
TI  - Volunteers keep communicating in 60 years of bad weather conditions.

PMID- 24313408
TI  - Award-winning nurse wants to end cases of mistaken identity.

PMID- 24313409
TI  - New vision for emergency care.

PMID- 24313410
TI  - Mobilising staff in the interests of patients.

PMID- 24313412
TI  - Gathering evidence of violence.

PMID- 24313419
TI  - Airway management in patients with brain injury.
AB  - Research has highlighted potential for changes in the technique and
      implementation of the bag-valve-mask system, a common piece of equipment used
      during resuscitation attempts to ventilate patients' lungs and deliver oxygen.
      This article analyses a critical incident involving a patient who experienced
      traumatic brain injury and required airway management. In reference to a
      reflective model, the article discusses the technique, implementation,
      complications and limitations of the bag-valve-mask system, and provides
      implications for practice. 

PMID- 24313420
TI  - Tranexamic acid in patients with major injuries and blood loss.
AB  - In the UK, care for people with major injuries has improved since the
      introduction of trauma networks and major trauma centres, and since ambulance
      services began to use specific triage tools to identify major trauma. The advent
      of consultant-led trauma teams in emergency departments and implementation of the
      relevant protocols have also raised the standard of trauma care. One such
      protocol governs the use of tranexamic acid (TXA), which is used to control
      bleeding. This drug is cheap and widely available, and can save lives if
      administered within three hours of injury. This article reviews two recent major
      studies of the effects of TXA on trauma patients. 

PMID- 24313421
TI  - Pre-hospital treatment of traumatic rhabdomyolysis.
AB  - Described as the pathological breakdown of skeletal muscle tissue in response to
      major injury, traumatic rhabdomyolysis iwas first recorded, during the second
      world war, a far greater understanding of its pathology has informed pre-hospital
      assessment and management of the condition. This article describes the aetiology
      of the condition and explores associated complications, such as acute respiratory
      distress syndrome, hyperkalaemia, acute renal failure and compartment syndrome
      resulting from prolonged limb entrapment. The article also reviews the literature
      about management of the condition for hospital and out-of-hospital settings.

PMID- 24313422
TI  - Sudden death in emergency care: responding to bereaved relatives.
AB  - Many emergency nurses find it difficult to support relatives whose loved ones are
      being resuscitated or to witness relatives' distress after their family members
      have died. When such events occur, emergency practitioners have few opportunities
      to engage effectively with relatives and so they must get it right first time,
      every time. Consequently, they need to be able to give information sensitively,
      and express compassion and empathy, to bereaved relatives. This article discusses
      these issues and includes exercises that practitioners can undertake to identify
      their personal strengths and professional competences when caring for suddenly
      bereaved relatives. 

PMID- 24313423
TI  - Lithium ion battery peformance of silicon nanowires with carbon skin.
AB  - Silicon (Si) nanomaterials have emerged as a leading candidate for next
      generation lithium-ion battery anodes. However, the low electrical conductivity
      of Si requires the use of conductive additives in the anode film. Here we report
      a solution-based synthesis of Si nanowires with a conductive carbon skin. Without
      any conductive additive, the Si nanowire electrodes exhibited capacities of over
      2000 mA h g(-1) for 100 cycles when cycled at C/10 and over 1200 mA h g(-1) when
      cycled more rapidly at 1C against Li metal. In situ transmission electron
      microscopy (TEM) observation reveals that the carbon skin performs dual roles: it
      speeds lithiation of the Si nanowires significantly, while also constraining the
      final volume expansion. The present work sheds light on ways to optimize lithium
      battery performance by smartly tailoring the nanostructure of composition of
      materials based on silicon and carbon. 

PMID- 24313424
TI  - The application of the central limit theorem and the law of large numbers to
      facial soft tissue depths: T-Table robustness and trends since 2008.
AB  - By pooling independent study means (x-), the T-Tables use the central limit
      theorem and law of large numbers to average out study-specific sampling bias and
      instrument errors and, in turn, triangulate upon human population means (MU).
      Since their first publication in 2008, new data from >2660 adults have been
      collected (c.30% of the original sample) making a review of the T-Table's
      robustness timely. Updated grand means show that the new data have negligible
      impact on the previously published statistics: maximum change = 1.7 mm at gonion;
      and <=1 mm at 93% of all landmarks measured. This confirms the utility of the
      2008 T-Table as a proxy to soft tissue depth population means and, together with
      updated sample sizes (8851 individuals at pogonion), earmarks the 2013 T-Table as
      the premier mean facial soft tissue depth standard for craniofacial
      identification casework. The utility of the T-Table, in comparison with shorths
      and 75-shormaxes, is also discussed. 

PMID- 24313425
TI  - Strengthening concept learning by repeated testing.
AB  - The aim of this study was to examine whether repeated testing with feedback
      benefits learning compared to rereading of introductory psychology key-concepts
      in an educational context. The testing effect was examined immediately after
      practice, after 18 days, and at a five-week delay in a sample of undergraduate
      students (n = 83). The results revealed that repeated testing with feedback
      significantly enhanced learning compared to rereading at all delays,
      demonstrating that repeated retrieval enhances retention compared to repeated
      encoding in the short- and the long-term. In addition, the effect of repeated
      testing was beneficial for students irrespectively of working memory capacity. It
      is argued that teaching methods involving repeated retrieval are important to
      consider by the educational system.

PMID- 24313426
TI  - [Lipid and lipoprotein levels in normal and complicated pregnancies].
AB  - OBJECTIVE: Lipid and lipoprotein levels during pregnancy and postpartum were
      compared in healthy pregnant women and in high risk pregnancy groups including
      women with pre-existing metabolic syndrome. The second half of a normal pregnancy
      is accompanied by hyperlipidaemia and glucose intolerance. Physiological response
      to pregnancy represents a transient excursion into a metabolic syndrome. DESIGN:
      Clinical study. SETTING: Department of Obstetrics and Gynaecology, Regional
      Hospital Pardubice, Faculty of Health Studies, University of Pardubice. METHODS:
      Fasting plasma lipid and lipoprotein levels were studied in 54 women during
      pregnancy and postpartum at the Regional Hospital Pardubice. The group of
      patients consisted of 25 healthy pregnant women,11 women with gestational
      diabetes, 9 women with diabetes type 1 and 9 women with pre-existing metabolic
      syndrome. The results were compared to measurements in 30 non-pregnant healthy
      controls. RESULTS: Total triglyceride levels in late gestation were at least but
      significantly (p < 0.001) elevated above those in non-pregnant controls in the
      group of patients with pre-existing metabolic syndrome. In the same group, in
      contrast with other groups, no changes in plasma cholesterol and LDL-cholesterol
      were found in late pregnancy. However, significant decline in HDL-cholesterol,
      when compared to non-pregnant controls, was observed 6 and 24 months postpartum
      only in the group of women with pre-existing metabolic syndrome (p < 0.01, p <
      0.001 respectively). CONCLUSION: The gynaecologist may be the first physician
      that a woman of reproductive age and with a metabolic syndrome encounters, it is
      important to suspect the presence of this syndrome and inform the woman about the
      most notable clinical implications.

PMID- 24313427
TI  - [The influence of hormone replacement therapy on the quality of life of women in
      menopause].
AB  - OBJECTIVE: The objective of the study was to find out the quality of life of
      women in menopause and the extent of their menopausal symptoms in relation with
      hormone replacement therapy. DESIGN: Interventional study. SETTING: Institute of
      Nursing and Midwifery, Faculty of Medicine, the University of Ostrava. METHODS: A
      sample was made up of 136 women from 41 to 58 years, who started to take hormone
      replacement therapy in order to improve their menopausal symptoms. For the
      assessment of the quality of life the WHOQOL - BREF questionnaire was used, and
      for the assessment of menopausal symptoms a Czech version of the standardized The
      Menopause - Specific Quality of Life Questionnaire MENQOL was used. Both
      questionnaires were given to the women twice - before the treatment was started
      and six months later. RESULTS: When comparing the quality of life in relation
      with the treatment we found out a significantly better assessment of the quality
      of life in all domains of the WHOQOL-BREF questionnaire, as well as in individual
      items of the assessment of the overall quality of life (Q1) and health (Q2), and
      also in all domains of the questionnaire of menopausal symptoms MENQOL, six
      months after the replacement treatment was initiated. Before the treatment women
      pointed out the biggest problems with weight gain (4.2), avoiding intimate
      relationships (4.1), hot flashes (4.0), the changes of the skin (3.9), night
      sweats (3.9), feelings of fatigue (3.9) and the loss of energy (3.7). Out of 28
      individual items of the questionnaire MENQOL a subjective improvement in the
      perception of menopausal symptoms were in 26 items, the biggest difference was in
      the item of night sweats (1.7), hot flashes (1.6), feelings of loss of energy
      (1.0) and fatigue (0.8). CONCLUSION: Hormone replacement therapy improves
      subjective assessment of the quality of life of women and the extent of
      menopausal symptoms already six months after a treatment initiation.

PMID- 24313428
TI  - [Incarcerated uterus in pregnancy - pitfalls of diagnosis, clinical course and
      therapy: two case reports].
AB  - OBJECTIVE: Analysis of two cases of incarcerated uterus during pregnancy. DESIGN:
      Two case reports. SETTING: Department of Gynecology and Obstetrics, Masaryk
      University, University Hospital Brno. METHODS AND RESULTS: In two cases of
      incarcerated uterus, which were resolved on Department of Gynaecology and
      Obstetrics, University Hospital Brno is shown a different clinical course,
      leading to the detection and solutions at different gestational weeks. The first
      case was detected in 31st week of pregnancy and was characterized by nearly
      asymptomatic course in a pregnant woman with a scar in the lower uterine segment
      after a previous caesarean section. The delivery was scheduled for the end of the
      36th week of pregnancy by iterative caesarean section. The second case was
      detected on the 27th week of pregnancy due to significant subjective difficulties
      of pregnant woman that impressed as acute event of abdomen. Despite all attempts
      at conservative therapy was necessary to terminate the pregnancy by caesarean
      section at 28 week of pregnancy due to the high risk of uterine rupture.
      CONCLUSION: Incarcerated uterus is a rare complication of pregnancy. Diagnostics
      complains varied clinical picture of the nonspecific subjective difficulties.
      Missed diagnosis can lead to a number of serious obstetric complications. In case
      of failure of conservative therapy and progression of difficulties is necessary
      to think about the real risk of uterine rupture. Before performing a caesarean
      section is essential knowledge of the mutual position of the lower uterine
      segment, urinary bladder and cervix.

PMID- 24313429
TI  - [Differential expression of microRNAs as the novel potential diagnostic tool for
      the endometrial carcinoma].
AB  - The most common gynecological malignancy, the endometrial carcinoma, is mostly
      diagnosed at early stages. However, diagnosis at advanced stages is accompanied
      by the high mortality rate. It is suggested that this cancer is one of the less
      studied female cancers. The necessity to establish novel diagnostic markers has
      led to investigations of small non-coding RNAs, particularly microRNAs, also in
      endometrial cancer. There have been found many microRNAs potentially associated
      with carcinogenesis and clinico-pathological data including prognosis for
      patients. Many microRNAs may also serve as diagnostic markers for non-invasive
      diagnostics using blood plasma. We reviewed extensively the published research
      focused on microRNAs that have been found deregulated particularly in tissue
      samples within the both major types of endometrial cancer (type 1 and type 2).
      They are presented in the view of their potential targets and mechanisms of
      action. Some microRNAs have been found deregulated also in blood plasma. There
      exists a high level of inconsistency across the studies as many microRNAs have
      been found only within one or a few studies so far. However, there are some
      microRNAs consistently deregulated as suggested several investigations. There
      remains the urgent need of more intensive research focused on the microRNAs and
      their regulatory role in endometrial cancer. Such a research should provide the
      basis for the introducing novel diagnostic tools into the clinical practice.

PMID- 24313430
TI  - [Pregnancy and delivery in a patient with pure 46,XY karyotype. Summary of actual
      knowledge about XY women].
AB  - TYPE OF STUDY: Summary review and a case report. SETTINGS: GEST IVF, Centre of
      Reproductive Medicine, Prague. INTRODUCTION: In scientific literature there two
      syndrome have been described in the presence of pure 46,XY karyotype when an
      individual is phenotypically and psychosexually identified as a woman. Androgen
      insensitivity syndrome (AIS) and pure gonadal dysgenesis XY (GD XY, Swyer
      syndrome). Thanks to the presence of a uterus in Swyer syndrome we can treat this
      type of sterility with donated oocytes. METHOD: The paper describes both
      syndromes from prenatal, genetical, endocrinological, oncological, reproductive
      and perinatological points of view. A case study concerning a patient with pure
      gonadal dysgenesis XY, who successfully became pregnant through a donated oocytes
      programme, is also described. The pregnancy progressed physiologically, and a
      healthy boy, 3820g/52cm, was delivered in term by ceasarean section. DISCUSSION:
      In world scientific literature at least fifteen successful pregnancies with pure
      gonadal dysgenesis XY have been described. In spite of the expectation of
      diminished uterine capacity, children are born to term with a normal delivery
      weight. CONCLUSION: This article should be considered as a summary of all actual
      knowledge about these patients. This article should be available and usefull for
      clinicians who come across XY females. The case study provides evidence that even
      an individual with male genetic gender can be pregnant and deliver a healthy
      child.

PMID- 24313431
TI  - Risk factors for endometrial cancer.
AB  - Endometrial cancer is the most common malignancy of women in developed countries,
      and its incidence is rising among pre- and postmenopausal women. In developed and
      numerous developing countries endometrial cancer, as well as other types of
      female cancers are an ever-increasing threat that may be explained, among other
      reasons, by increased life expectancy and changes in lifestyle factors.
      Endometrial cancer is more common in postmenopausal women than in premenopausal
      women. Through a review of the literature it was found that the risk of
      endometrial cancer is positively correlated with older age, early menarche & late
      menopause, obesity, family history of endometrial cancer (especially among close
      relatives), radiation exposure, and infertility particularly in the presence of
      Polycystic Ovarian Syndrome. Long-term use of unopposed oestrogens for hormone
      replacement therapy also increases the risk of endometrial cancer. Caucasians
      have a higher incidence of endometrial cancer than African or Asian women. Obese
      women were found to be at high risk for developing endometrial cancer, while
      diabetes, hypertension, and geographical and socioeconomic factors are still
      inconclusive. Finally, smoking is considered as a protective factor against
      endometrial cancer due to its anti- estrogenic effect.

PMID- 24313432
TI  - [Fulminant course of HELLP syndrome with lethal outcome - case report].
AB  - OBJECTIVE: To present a case of death of a patient with fulminant course of HELLP
      syndrome in 32nd week of pregnancy. DESIGN: Case report. SETTING: Department of
      Obstetrics and Gynecology, Hospital Kladno. CASE REPORT: We report a case of 29
      years old primigravida in 32nd week of pregnancy, which was admitted to the
      hospital in a serious condition with cephalea, vomiting and progressive full-body
      swelling. During the entrance examination the patient looses consciousness, due
      to critical pressure an emergency caesarian section is performed. Laboratory
      values correspond to a fully developed HELLP syndrome, which gradually progresses
      from class III to class I of Mississippi classification. The patient's condition
      required further surgical interventions including hysterectomy. Despite intensive
      therapy and multidisciplinary cooperation a gradual failure of vital functions
      and death of the patient followed. CONCLUSION: Presenting this critical situation
      the authors want to emphasize the need of early diagnosis and subsequent
      comprehensive treatment in cooperation with other disciplines in the care of
      critically endangered patient on delivery room.

PMID- 24313433
TI  - [Comment on article "Fulminant course of HELLP syndrome with lethal outcome -
      case report"].

PMID- 24313434
TI  - [Preeclampsia and thrombin generation test].
AB  - OBJECTIVE: Acquiring new information to allow prediction of the development of
      diseases associated with impaired coagulation. Design effective preventive
      measures most serious diseases (TEN) in the fields of gynecology and obstetrics.
      For pregnant women with preeclampsia, hypertension compared with women with
      normal pregnancies could lead to increased thrombin generation due to the
      synergistic effect of thrombotic risk factors. Based on the results and found
      statistically significant differences between the groups among pregnant can
      select for a higher risk of developing deep vein thrombosis. This risk group
      could then greatly benefit from more stringent follow-up and possible preventive
      treatment prophylactic doses of LMWH in reducing maternal and perinatal morbidity
      and mortality. DESIGN: Prospective study. SETTING: Department of Obstetrics and
      Gynecology, University Hospital Olomouc. METHODS: In early pregnancy - during
      pregnancy standard samples (up to the end of the first trimester) patients venous
      blood was sampled and they completed information questionnaire. A second sampling
      was carried out between 24 to 28 week, the third sample and between 36th to 40th
      week. Obtained blood samples were subsequently processed in the coagulation
      laboratory Hemato-Oncology Clinic and Olomouc. The blood samples were
      investigated protein C and S, antithrombin, FVIII level, FII, Leiden, and plasma
      endothelial microparticles, and lupus anticoagulant and APC resistance
      standardized methodologies. Thrombin generation was determined thrombin
      generation test. Thrombin generation was measured fully automatically using a kit
      (Technothrombin TGA, Technoclone, Vienna, Austria) and analyzer Ceveron Alpha
      (Technoclone, Vienna, Austria) with fully automatic analysis software. As the
      main parameter is evaluated by the maximum thrombin generation, at the same time,
      however, was also detected in the total amount of thrombin and the time until the
      beginning of the formation of thrombin. RESULTS: In the period 2008-2011 were
      analyzed blood samples of 303 healthy pregnant women. 215 women, ie 71% were
      nuliparas, 60 women, ie 19.8% were primiparas, 28 women, 9,2% were secundiparas.
      The average age of pregnant women was 28.6 years(+/- 3.8 years). The average
      maternal weight at the beginning of pregnancy was 63.6 kg (+/- 7.8 kg). Of the
      303 women in 18 (6%) developed slight to moderate degree of preeclampsia or HELLP
      syndrome with varying severity of clinical manifestations. 20 mothers (6.6%) gave
      birth prematurely terminated before 37 week of pregnancy. 3 pregnancies (0.9%)
      were discontinued due to genetic indication for fetal birth defect. The complete
      study protocol (sampling in all three trimesters) thus completed 280 pregnancies.
      Of the three evaluated, parameter Lag time, ETP and peak we observed significant
      differences when comparing physiological pregnancies and pregnancies with
      preeclampsia (Table 3 and Figure 5-7), the statistical level of p < 0.01. In
      pregnancies with chronic hypertension, these differences were not significant.
      Comparison of 18 pregnancies, in which the III. trimester developed preeclampsia
      with other pregnant with physiological pregnancy did not show statistically
      significant differences in I. and II. trimester. The results suggest the
      activation of coagulation through the late stages of pregnancy. Results are
      influenced by strong clinical variability of disease. In severe and early
      preeclampsia this activation and significant differences begin much earlier.
      CONCLUSION: We demonstrated significantly higher activation of thrombin
      generation in women with preeclampsia [10]. Changes in preeclampsia are
      characterized by increased generation of thrombin in plasma. This fact may
      explain the partial success of the clinical use of aspirin in preeclampsia. In
      the third trimester, during the manifestation of the disease, patients with
      preeclampsia have significantly higher ETP compared to patients with a normal
      pregnancies. Pregnant women with chronic hypertension also show a slight increase
      in the activation of thrombin. However, these results are not statistically
      significant. Examination of coagulation in the first and second trimester in
      women who later developed preeclampsia, showed no statistically significant
      differences and thus can not be used in this case as predictive, but only as a
      diagnostic test.

PMID- 24313435
TI  - [Lymphedema after vulvar cancer surgery. A prospective study].
AB  - INTRODUCTION: Prospective detection of postoperative lymphedema of the lower
      limbs (LLL) in patients after surgery for vulvar cancer using different
      examination methods and their comparison. DESIGN: Prospective clinical study.
      SETTING: Department of Obstetrics and Gynecology, 2nd Medical Faculty of the
      Charles University and University Hospital Motol, Prague. METHODS: Totally 36
      women were followed after surgery for vulvar cancer. Due to the radicality of
      surgery the patients were divided into conservative (sentinel lymph node biopsy)
      and radical (inguinofemoral lymphadenectomy) group. Lower limbs were
      preoperatively and 3, 6 and 12 months after surgery assessed for the presence of
      lymphedema by measuring of circumferences, multifrequency bioelectrical impedance
      analysis (MFBIA) and subjective evaluation of patients. RESULTS: The prevalence
      of lower limb lymphedema 12 months after surgery diagnosed by subjective
      evaluation reached 19,44%, by circumference measurement 38,89% and with MFBIA
      66,67%. The prevalence of lymphedema after inguinofemoral lymphadenectomy
      diagnosed by circumference measurement was in 12 months after surgery higher
      (45.83%) than after the conservative surgery (25%). Risk factors were evaluated
      12 months after surgery (age, BMI, adjuvant radiotherapy, type of surgery) and
      none of them were found to be statistically significant for the development of
      the lower limbs lymphedema. CONCLUSION: The prevalence of lymphedema
      significantly depends on the diagnostic method, because they capture lymphedema
      in its various stages. Due to the high sensitivity MFBIA can be used for the
      detection of early stages of lymphedema. Preoperative measurement of the lower
      limbs is important for early detection of postoperative lymphedema.

PMID- 24313436
TI  - [Activities and responsibilities of workers in embryologic and andrologic
      laboratories in assisted reproduction centers].
AB  - This paper presents the current status and rules for the laboratory staff
      activities and their competences in the centers of assisted reproduction. The
      rules were processed by the members of the Association of Reproductive Embryology
      (ARE) committee under the current legislation. Committee members of the Czech
      Sterility and Assisted Reproduction Society and Czech Gynecology and Obstetric
      Society approved these rules as obligatory for assisted reproduction centres in
      Czech Republic.

PMID- 24313437
TI  - [Doctors specialty training in obstetrics and gynecology at university medical
      schools: 2012-2013].
AB  - OBJECTIVE: The paper addresses transfer of doctors specialty training from the
      national Institute of postgraduate medical education (IPVZ) to University Medical
      Schools (UMS) with the special focus to Obstetrics and Gynecology (OG). METHODS:
      The National Specialty Board (NSB) has been established. NSB tasks include
      definition of inclusion criteria and process of specialty choice at UMS. In OG
      specialty there are defined mid-term and final postgraduate training courses and
      other requirements for final specialty exam (FSE) - in particular trainees
      scientific work and surgery done with the supervision of NTB member. The system
      of FSE, its content, application, reimbursement and mechanisms are described in
      details. RESULTS: In the whole country in 2012 there have been done 864 FSE in
      all basic medical specialties, which took place at seven UMS. Autumn semester
      terms has been utilized significantly more than spring terms (57% vs. 43%). There
      have been differences in the numbers of specialties and also numbers of
      candidates in each specialty among different UMS. In total 94% of applicants
      succeed in the FSE. In 2012 within OG specialty training there has been held 56
      FSE - 24 exams on five UMS in spring term and 32 (57%) exams only on two UMS in
      autumn term. In the spring 2013 FSE were organized on 1st LF UK in Prague with 23
      applicants, from which 22 successfully passed. During autumn 2013 the FSE in OG
      will be held on LF UP in Olomouc with 44 applicants for final postgraduate
      training course and 39 candidates for FSE. CONCLUSION: Within OG specialty the
      transfer of doctors specialty training from IPVZ to UMS has been successfully
      managed. The NSB in OG specialty closely cooperates with past IPVZ and the
      Accreditation Commission of the Czech Ministry of Health. Thus continuity,
      quality and continuous enhancement of specialty training program in OG in Czech
      Republic is assured.

PMID- 24313438
TI  - External validation of structure-biodegradation relationship (SBR) models for
      predicting the biodegradability of xenobiotics.
AB  - Biodegradation is an important mechanism for eliminating xenobiotics by
      biotransforming them into simple organic and inorganic products. Faced with the
      ever growing number of chemicals available on the market, structure
      biodegradation relationship (SBR) and quantitative structure-biodegradation
      relationship (QSBR) models are increasingly used as surrogates of the
      biodegradation tests. Such models have great potential for a quick and cheap
      estimation of the biodegradation potential of chemicals. The Estimation Programs
      Interface (EPI) SuiteTM includes different models for predicting the potential
      aerobic biodegradability of organic substances. They are based on different
      endpoints, methodologies and/or statistical approaches. Among them, Biowin 5 and
      6 appeared the most robust, being derived from the largest biodegradation
      database with results obtained only from the Ministry of International Trade and
      Industry (MITI) test. The aim of this study was to assess the predictive
      performances of these two models from a set of 356 chemicals extracted from
      notification dossiers including compatible biodegradation data. Another set of
      molecules with no more than four carbon atoms and substituted by various
      heteroatoms and/or functional groups was also embodied in the validation
      exercise. Comparisons were made with the predictions obtained with START
      (Structural Alerts for Reactivity in Toxtree). Biowin 5 and Biowin 6 gave
      satisfactorily prediction results except for the prediction of readily degradable
      chemicals. A consensus model built with Biowin 1 allowed the diminution of this
      tendency. 

PMID- 24313439
TI  - Evaluation criteria for the quality of published experimental data on
      nanomaterials and their usefulness for QSAR modelling.
AB  - Nowadays nanotechnology is one of the most promising areas of science. The number
      and quantity of synthesized nanomaterials increase exponentially, therefore it is
      reasonable to expect that comprehensive risk assessment based only on empirical
      testing of all novel engineered nanoparticles (NPs) will very soon become
      impossible. Hence, the development of computational methods complementary to
      experimentation is very important. Quantitative structure-property relationship
      (QSPR) and quantitative structure-activity relationship (QSAR) models widely used
      in pharmaceutical chemistry and environmental science can also be modified and
      adopted for nanotechnology to predict physico-chemical properties and toxicity of
      empirically untested nanomaterials. All QSPR/QSAR modelling activities are based
      on experimentally derived data. It is important that, within a given data set,
      all values should be consistent, of high quality and measured according to a
      standardized protocol. Unfortunately, the amount of such data available for
      engineered nanoparticles in various data sources (i.e. databases and the
      literature) is very limited and seldom measured with a standardized protocol.
      Therefore, we have proposed a framework for collecting and evaluating the
      existing data, with the focus on possible applications for computational
      evaluation of properties and biological activities of nanomaterials. 

PMID- 24313440
TI  - Straightforward MIA-QSTR evaluation of environmental toxicities of aromatic
      aldehydes to Tetrahymena pyriformis.
AB  - Aldehydes are toxic environmental contaminants which cause severe health hazards.
      There is a growing need by industries and regulatory agencies for the development
      of tools able to assess the potential hazardous effects of chemicals on living
      organisms. In this background, multivariate image analysis combined with
      quantitative structure-toxicity relationships (MIA-QSTR) was used to evaluate the
      toxicity of aromatic aldehydes to Tetrahymena pyriformis. The techniques of
      genetic algorithm-partial least squares (GA-PLS) were applied effectively as MIA
      descriptor selection and mapping tools. In MIA-QSTR evaluation, pixels of 2D
      images of chemical structures could be used to recognize physicochemical
      information and predict changes in the toxicities. The resulting MIA-QSTR
      explains 90.3% leave-one-out predicted variance and 93.1% external predicted
      variance. The MIA-QSTR/GA-PLS performances were validated using various
      evaluation techniques such as cross-validation, applicability domain and Y
      scrambling procedures, suggesting that the present methodology together with
      mechanistic interpretation may be useful to evaluate toxicity, safety and risk
      assessment of toxic environmental contaminants. 

PMID- 24313441
TI  - Synthesis, characterization, and aqueous self-assembly of octenylsuccinate Oat
      beta-glucan.
AB  - Amphiphilic oat beta-glucan derivatives carrying octenylsuccinic groups as
      hydrophobic moieties have been synthesized. Materials with a different degree of
      substitution (DS) and weight-average molecular weight (Mw) for oat beta-glucan
      were prepared and characterized using elemental analysis, infrared (IR)
      spectroscopy, and high performance size exclusion chromatography (HPSEC). Dynamic
      light scattering (DLS), fluorescence spectroscopy, and transmission electron
      microscopy (TEM) revealed that octenylsuccinate oat beta-glucan (OSG) can self
      assemble into spherical micelles in water with an average size ranging from 175
      to 600 nm. OSG micelles were negatively charged as indicated by zeta-potential
      measurement. The critical micelle concentration (CMC) of OSGs varied from 0.206
      to 0.039 mg/mL, depending on the DS and Mw of the oat beta-glucan. It was found
      that the presence of OSG micelles in aqueous solution could significantly enhance
      the solubility of curcumin by 880 fold. Thus, OSG might have great potential in
      applications as hydrophobic nutrient delivery carriers. 

PMID- 24313442
TI  - Quantifying the effect of competition for detection between coeluting peptides on
      detection probabilities in mass-spectrometry-based proteomics.
AB  - There are many factors that contribute to the variation in detection
      probabilities of proteins in LC-MS/MS experiments, and currently little is known
      about their relative importance. In this study, we analyze the effect of
      competition for detection between coeluting peptides on peptide detection
      probability. Using a novel method for estimating peptide detection probabilities,
      we show that these probabilities can vary by an order of magnitude between
      peptides that elute from the liquid chromatograph at the same time as many other
      peptides and those that elute with fewer other peptides. To explore these
      results, we use a mathematical model to show that competition for detection
      between peptides is expected to be a major source of missed detections in complex
      mixtures because there will be many MS/MS scanning intervals that contain more
      coeluting peptides than can be subjected to MS/MS analysis. Our data and
      simulation results show that the number of coeluting peptides is a primary
      determinant of whether a peptide will be detected. In our data, this had a
      several-fold larger effect on peptide detection probability than did peptide
      abundance. Furthermore, the distribution of elution times for the most frequently
      detected peptides was strongly shifted toward values where there were few
      coeluting peptides, indicating that the number of coeluting peptides is a major
      determinant of whether a peptide is proteotypic. 

PMID- 24313443
TI  - Development of ISSR-derived SCAR marker-targeted PCR for identification of
      Aspergillus section Flavi members.
AB  - Aspergillus section Flavi is a heterogeneous fungal cluster including some of the
      most economically important Aspergillus species. The section is comprised of
      toxigenic and nontoxigenic aspergilli that are phenotypically undistinguishable.
      The aim of this study was to develop a genetic marker specific to Aspergillus
      section Flavi on the whole. Based on inter-simple sequence repeat (ISSR)
      fingerprinting profiles of major Aspergillus section Flavi members, a sequence
      characterized amplified region (SCAR) marker was identified. Primers were
      designed in the conserved regions of the SCAR marker and were utilized in a PCR
      for concurrent identification of major members of the section. The detection
      level of the SCAR-PCR was found to be 0.1 ng purified DNA, and when applied to 45
      naturally contaminated food samples, 28 samples were found infected with
      Aspergillus section Flavi members. The present SCAR-PCR is rapid and less
      cumbersome unlike conventional identification techniques. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Identification of Aspergillus section Flavi members is important
      owing to their impact on human health and economy. The ISSR-based SCAR-PCR
      developed in this study is superior over the other existing Aspergillus section
      Flavi detection systems due to its simplicity and minimal requirement of sample
      handling. This PCR could be a supplementary strategy to time-consuming and rather
      ambiguous conventional polyphasic detection techniques and a reliable tool for
      high-throughput sample analysis.

PMID- 24313444
TI  - Etanercept decreases synovial expression of tumour necrosis factor-alpha and
      lymphotoxin-alpha in rheumatoid arthritis.
AB  - OBJECTIVES: Etanercept is an effective tumour necrosis factor (TNF)-alpha
      inhibitor drug with the unique ability to block not only TNF-alpha but also
      lymphotoxin (LT)-alpha, at least in vitro. We aimed to investigate the in vivo
      effect of etanercept on synovial expression of TNF-alpha and LT-alpha. METHOD:
      Synovial biopsies from 12 rheumatoid arthritis (RA) patients started on
      etanercept and 11 RA patients started on infliximab were obtained at baseline and
      8 weeks after treatment initiation. Synovial expression of TNF-alpha and LT-alpha
      was evaluated by immunohistochemistry followed by computer-assisted image
      analysis. Differences between paired samples were analysed by the Wilcoxon test
      and between groups by the Mann-Whitney test. A p-value < 0.05 was considered
      statistically significant. RESULTS: Six out of the 12 of the patients started on
      etanercept achieved an American College of Rheumatology (ACR)50 response.
      Macroscopic evaluation of the joints during arthroscopy revealed a significant
      decrease of local inflammation mainly in good ACR50 responders. Synovial
      expression of both LT-alpha and TNF-alpha decreased but the differences did not
      reach statistical significance at a group level. By contrast, a significant
      decrease in both LT-alpha and TNF-alpha was observed when only good ACR50
      responders were analysed. Despite higher levels of baseline synovial TNF-alpha in
      the good responders, neither baseline LT-alpha nor TNF-alpha could predict
      clinical response after 8 weeks. A decreasing trend of the synovial levels of LT
      alpha was also observed in good responders to infliximab, but the difference did
      not reach statistical significance. CONCLUSIONS: Etanercept treatment modulates
      the synovial expression of both TNF-alpha and LT-alpha in vivo, a mechanism that
      might partly explain its clinical efficacy in RA.

PMID- 24313446
TI  - A randomized controlled trial of the effectiveness of planning strategies in the
      adherence to medication for coronary artery disease.
AB  - AIM: To examine the effect of action and coping planning strategies in the
      adherence to medication among outpatients with coronary artery disease.
      BACKGROUND: Action and coping planning strategies are based on implementation
      intention, which requires self-regulation by the individual, to prioritize
      intentionally planned responses over learned or habitual ones, from daily
      routines to stressful situations. DESIGN: Randomized controlled trial. METHODS:
      Participants (n = 115) were randomized into intervention (use of action and
      coping planning strategies, n = 59) or control (usual care, n = 56) groups. The
      study was conducted between June 2010-May 2011 in two in-person visits: baseline
      and 2-month follow-up. Participants in the intervention group received telephone
      reinforcement between baseline and 2-month follow-up. Adherence to medication for
      cardioprotection and symptoms relief was evaluated by proportion of adherence,
      global measure of adherence evaluation and Morisky Self-Reported Measure of
      Medication Adherence Scale at both baseline and 2-month follow-up. FINDINGS: When
      using the measure of global measure of adherence, participants in the
      intervention group reported adherence to therapy more often than controls (odds
      ratio = 5.3), but no statistically significant change was observed in the other
      two outcome measures. CONCLUSION: This study has shown that individuals who use
      action and coping planning report higher adherence to drug treatment, when
      measured by the global adherence evaluation. Further studies with longer follow
      ups are needed to assess if the effect of planning strategies has long-term
      duration.

PMID- 24313445
TI  - The role of acculturation and collectivism in cancer screening for Vietnamese
      American women.
AB  - The aim of this study was to examine the influence of demographic variables and
      the interplay between collectivism and acculturation on breast and cervical
      cancer screening outcomes among Vietnamese American women. Convenience sampling
      was used to recruit 111 Vietnamese women from the Richmond, VA, metropolitan
      area, who participated in a larger cancer screening intervention. All
      participants completed measures on demographic variables, collectivism,
      acculturation, and cancer-screening-related variables (i.e., attitudes, self
      efficacy, and screening behavior). Findings indicated that collectivism predicted
      both positive attitudes and higher levels of self-efficacy with regard to breast
      and cervical cancer screening. Collectivism also moderated the relationship
      between acculturation and attitudes toward breast cancer screening such that for
      women with low levels of collectivistic orientation, increasing acculturation
      predicted less positive attitudes towards breast cancer screening. This
      relationship was not found for women with high levels of collectivistic
      orientation. The current findings highlight the important roles that
      sociodemographic and cultural variables play in affecting health attitudes, self
      efficacy, and behavior among Vietnamese women. The findings potentially inform
      screening programs that rely on culturally relevant values in helping increase
      Vietnamese women's motivation to screen. 

PMID- 24313447
TI  - The vagus nerve attenuates fulminant hepatitis by activating the Src kinase in
      Kuppfer cells.
AB  - The parasympathetic nervous system has been known to modify innate immune
      responses. In animal models, acetylcholine (Ach) released from the distal ends of
      nerves has been shown to inhibit inflammatory responses such as endotoxic shock,
      pancreatitis, intestinal inflammation, etc. However, its role in LPS-induced
      fulminant hepatitis remains to be elucidated. Here, we demonstrate that the vagus
      nerve acts as a suppressor in the liver after challenge with LPS plus D-gal. The
      vagus nerve acts through the alpha7 AchR expressed on the surface of Kupffer
      cells, inhibiting the production of the proinflammatory cytokines TNF and IL-6. A
      mechanism study revealed that the suppressive effect of Ach may occur through the
      activation of Src kinase and subsequent inhibition of the Myd88 signal pathway.
      Our study has suggested a suppressive role of vagus nerve in the modulation of
      liver inflammatory responses, which should be noticed during clinical massive
      hepatectomy and liver transplantation. The nicotinic anti-inflammatory pathway
      may also be a potential target for sepsis after liver transplantation. 

PMID- 24313448
TI  - Pneumococcal infection in adults: burden of disease.
AB  - To overview the present global burden of pneumococcal disease is important
      because new preventive measures such as the pneumococcal conjugate vaccine 13 are
      currently being evaluated. Pneumococcal disease is roughly divided into non
      invasive and invasive disease. The burden of non-invasive pneumococcal disease in
      adults is mainly determined by community-acquired pneumonia. Pneumococcal
      pneumonia has high incidence rates and carries a high mortality risk, especially
      in the elderly. Within the cluster of invasive pneumococcal diseases, pneumonia
      also represents the most common infectious source. Incidence and mortality rates
      of both non-invasive and invasive disease have changed as a result of
      pneumococcal vaccination in children. However, especially elderly patients with
      comorbidities remain vulnerable to morbidity and mortality caused by pneumococcal
      disease. The current review summarizes the current knowledge on the epidemiology
      including outcome of the main clinical forms of pneumococcal disease, with a
      special focus on elderly patients. Furthermore, the economic burden and future
      vaccine strategies are briefly discussed. 

PMID- 24313449
TI  - Isolation of Bacteroides from fish and human fecal samples for identification of
      unique molecular markers.
AB  - Bacteroides molecular markers have been used to identify human fecal
      contamination in natural waters, but recent work in our laboratory confirmed
      cross-amplification of several human-specific Bacteroides spp. assays with fecal
      DNA from fish. For identification of unique molecular markers, Bacteroides from
      human (n = 4) and fish (n = 7) fecal samples were cultured and their identities
      were further confirmed using Rapid ID 32A API strips. The 16S rDNA from multiple
      isolates from each sample was PCR amplified, cloned, and sequenced to identify
      unique markers for development of more stringent human-specific assays. In human
      feces, Bacteroides vulgatus was the dominant species (75% of isolates), whereas
      in tilapia feces, Bacteroides eggerthii was dominant (66%). Bacteroides from
      grass carp, channel catfish, and blue catfish may include Bacteroides uniformis,
      Bacteroides ovatus, or Bacteroides stercoris. Phylogenic analyses of the 16S rRNA
      gene sequences showed distinct Bacteroides groupings from each fish species,
      while human sequences clustered with known B. vulgatus. None of the fish isolates
      showed significant similarity to Bacteroides sequences currently deposited in
      NCBI (National Center for Biotechnology Information). This study expands the
      current sequence database of cultured fish Bacteroides. Such data are essential
      for identification of unique molecular markers in human Bacteroides that can be
      utilized in differentiating fish and human fecal contamination in water samples. 

PMID- 24313450
TI  - Serotype distribution of invasive Streptococcus pneumoniae in Canada after the
      introduction of the 13-valent pneumococcal conjugate vaccine, 2010-2012.
AB  - The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very
      effective in reducing invasive pneumococcal disease (IPD) in children; however,
      increases of non-PCV7 serotypes have subsequently offset some of these
      reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional
      serotypes was implemented between 2010 and 2011, and in 2012 changes in the
      incidence of disease and the distribution of IPD serotypes began to emerge. The
      incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per
      100 000 population between 2010 and 2012; however, the incidence in ages >=5
      years remained relatively unchanged over the 3-year period, at about 9.7 cases
      per 100 000 population. From 2010 to 2012, PCV13 serotypes declined significantly
      from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and
      from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children >=5 years of age.
      Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A
      decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from
      14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727)
      to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to
      10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates
      of antimicrobial resistance were observed with clarithromycin (23%), penicillin
      using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim
      sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions
      in the incidence of disease suggest that current immunization programs in Canada
      are effective in reducing the burden of IPD in children. While we acknowledge the
      limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this
      study represents one of the first descriptions of the potential impact of the
      PCV13 vaccine in the Canadian population. Continued surveillance will be
      important to recognize replacement serotypes, to determine the extent of herd
      immunity effects in nonpaediatric populations, and to assess the overall
      effectiveness of PCV13 in reducing IPD in Canada. 

PMID- 24313451
TI  - Deubiquitinating activity of Sdu1, a putative member of the PPPDE peptidase
      family, in Schizosaccharomyces pombe.
AB  - The Schizosaccharomyces pombe sdu+ gene encoding a putative member of the PPPDE
      (Permuted Papain fold Peptidases of DsRNA viruses and Eukaryotes) superfamily was
      cloned into an Escherichia coli - yeast shuttle vector pRS316, resulting in the
      recombinant plasmid pYSTP. The determined nucleotide sequence carries 1207 bp,
      which would encode a protein of 201 amino acid residues. The S. pombe cells
      harboring pYSTP contained higher sdu1+ mRNA and deubiquitinating activity levels
      than the vector control cells, indicating that the sdu1+ gene is functioning.
      They exhibited a better growth in normal rich medium than the vector control
      cells. When shifted into the fresh medium containing hydrogen peroxide,
      menadione, or sodium nitroprusside, the S. pombe cells harboring pYSTP were able
      to grow reasonably well, while the growth of the vector control cells was
      arrested. The reactive oxygen species and total glutathione levels of the S.
      pombe cells harboring pYSTP were lower and higher than those of the vector
      control cells under the same stressful conditions, respectively. They exhibited a
      lower nitric oxide level than the vector control cells when subjected to sodium
      nitroprusside. Taken together, the sdu1+ gene encodes an actual protein having
      deubiquitinating activity and is involved in the response against oxidative and
      nitrosative stresses in S. pombe.

PMID- 24313452
TI  - Multiplex polymerase chain reaction using ethidium monoazide and propidium
      monoazide for distinguishing viable and dead cells of arcobacters in biofilm.
AB  - This paper concerns the formation of biofilm in bacteria of the genus Arcobacter.
      A multiplex polymerase chain reaction (PCR) method was introduced and optimized
      for detecting biofilm while using the intercalating dyes ethidium monoazide (EMA)
      and propidium monoazide (PMA), first for analysis of strains of the genus
      Arcobacter from a collection, and then applied to samples of prepared biofilms.
      The results of the study indicate considerable variability among species of
      bacteria within the genus Arcobacter. The EMA-PMA PCR method can distinguish
      viable cells from dead cells and is therefore suitable for determining the
      viability of cells. 

PMID- 24313453
TI  - Species diversity of corticolous myxomycetes in Tianmu Mountain National Nature
      Reserve, China.
AB  - The species diversity of corticolous myxomycetes on 4 vegetation types in the
      Tianmu Mountain National Natural Reserve, eastern China, was examined from 2011
      to 2012. A total of 1440 moist chamber cultures were prepared with bark samples,
      which yielded several hundred collections representing 42 species in 20 genera.
      It was found that 79% of cultures produced some evidence (either plasmodia or
      fruiting bodies) of myxomycetes. Eight species (Comatricha elegans, Cribraria
      confusa, Licea pusilla, Cribraria microcarpa, Collaria arcyrionema, Licea
      biforis, Arcyria cinerea, and Clastoderma debaryanum) were abundant (exceeding 3%
      of all records), but about a third of all species were classified as rare.
      Species richness (S = 33) and diversity (exp[H'] = 16.60, S/G = 1.74) of
      corticolous myxomycetes were the most diverse in the deciduous broadleaf forest.
      The species recorded from coniferous forest showed the lowest species richness (S
      = 21) but the highest evenness (J' = 0.91). The cluster analyses were based on
      the Bray-Curtis similarity matrix, and the results indicated that corticolous
      myxomycete assemblages were distributed by a seasonal and annual pattern.
      Canonical correspondence analysis showed that season and pH were key factors in
      determining species distribution. 

PMID- 24313454
TI  - Hemagglutinin protein of measles virus induces apoptosis of HeLa cells via both
      extrinsic and intrinsic pathways.
AB  - In this study, we investigated the potential for different components of the
      measles virus (MV) to induce apoptosis of HeLa cells and explored the apoptotic
      molecular mechanisms. After testing the 2 envelope glycoproteins hemagglutinin
      (H) and fusion (F), we found that MV H alone was sufficient to induce the
      apoptosis of HeLa cells, whereas MV F did not. MV F also had no influence on MV-H
      mediated apoptosis. MV H could induce cellular apoptosis in HeLa cells through
      its interaction with the cellular receptor CD46 via both the TRAIL-mediated
      extrinsic pathway and the mitochondria-controlled intrinsic pathway, and that
      cross talk between these 2 pathways occurred during the process. These findings
      extend the functions of MV envelope glycoproteins in the pathogenesis of MV
      infection and suggest that MV H may be a potential therapeutic in the treatment
      of some cancers. 

PMID- 24313455
TI  - Abundance and composition of denitrifiers in response to Spartina alterniflora
      invasion in estuarine sediment.
AB  - Nitrite reduction is regulated by nitrite reductase encoded by nirK and nirS
      genes. This study aimed to investigate the abundance and composition of nirK- and
      nirS-containing denitrifiers in response to Spartina alterniflora invasion at the
      Jiulong River estuary, China. The sediment samples (depth: 0-5.0 and 5.1-20 cm)
      were collected from 3 vegetation zones, 1 dominated by the exotic plant S.
      alterniflora, 1 dominated by the native plant Kandelia candel, and 1 dominated by
      the native plant Cyperus malaccensis, and from an unvegetated flat zone. nirK-
      and nirS-containing denitrifier population sizes were lower in the invaded and
      nonvegetated zones than in those dominated by native K. candel and C.
      malaccensis, which were impacted by depth - vegetation species interaction. The
      ratios of nirS to nirK abundance ranged from 42.10 to 677.27, with the lowest
      ratio found for the upper layer in the invaded zone. The nirK-containing
      denitrifier compositions showed a 35% similarity between invaded zone and others.
      Most of the sequences of nirK genes recovered from the S. alterniflora zone were
      specific and distinct from those of nirK genes recovered from other vegetation
      types; nirS genes in the invaded zone were highly divergent. These results reveal
      that S. alterniflora invasion has a significant effect on the abundance and
      composition of both nirK- and nirS-containing denitrifiers, and nirS-containing
      denitrifiers were less responsive to invasion than nirK-containing denitrifiers. 

PMID- 24313456
TI  - Bioremediation of oily hypersaline soil and water via potassium and magnesium
      amendment.
AB  - Ten hydrocarbonoclastic halobacterial species and 5 haloarchaeal species that had
      been isolated on a mineral medium with oil as the sole carbon source grew better
      and consumed more crude oil, as measured by gas-liquid chromatography, in media
      receiving between 0.50 and 0.75 mol/L KCl and between 1.50 and 2.25 mol/L MgSO4.
      Chemical analysis revealed that within a certain limit, the higher the KCl and
      MgSO4 concentrations in the medium, the more K+ and Mg2+, respectively, was
      accumulated by cells of all the tested halobacteria and haloarchaea. Also, in
      experiments in which total natural microbial consortia in hypersaline soil and
      water samples were directly used as inocula, the consumption of hydrocarbons was
      enhanced in the presence of the above given concentrations of KCl and MgSO4. It
      was concluded that amendment with calculated concentrations of K+ and Mg2+ could
      be a promising practice for hydrocarbon bioremediation in hypersaline
      environments.

PMID- 24313457
TI  - Prediction of postpartum blood transfusion--risk factors and recurrence.
AB  - OBJECTIVE: The aim was to find clinically useful risk factors for postpartum
      transfusion and to assess the joint predictive value in a population of women
      with a first and second delivery. METHODS: All Danish women with a first and
      second delivery from January 2001 to September 2009 who gave birth in a hospital
      that reported transfusion of red blood cells to a national database: A total of
      96 545 women were included. RESULTS: Retained placental tissue explained more
      than all other risk factors in vaginal deliveries. Retained placental tissue at
      first delivery was associated with postpartum transfusion at a second vaginal
      delivery, and may also be used as an early predictor in parallel with a history
      of either placental abruption, postpartum transfusion or caesarean delivery. The
      positive predictive values of having more than one risk factor was low (2.2%
      2.7%). CONCLUSIONS: Prediction of postpartum transfusion is difficult. Retained
      placental tissue is the strongest predictor of postpartum blood transfusion in
      vaginal deliveries. Retained placental tissue is usually diagnosed for the first
      time when the bleeding starts, which limits the clinical value of prediction. We
      need tools for an early diagnosis of retained placenta to intervene early before
      transfusion is needed.

PMID- 24313459
TI  - Vertical arrays of SiO2 micro/nanotubes templated from Si pillars by chemical
      oxidation for high loading capacity buoyant aquatic devices.
AB  - A simple and facile method to fabricate SiO2 micro- or nanotubes has been
      demonstrated based on room temperature wet chemical oxidation of a porous layer
      of Si pillar templates that have been prepared by metal-assisted chemical etching
      (MaCE). Under typical conditions, Si pillars produced by the MaCE have been found
      to be covered with a thin nanoporous Si layer. The porous Si skin layer has been
      chemically oxidized by simple dipping in AgNO3 solution at room temperature,
      which has led to seamless SiO2 shell layer thanks to the accompanying volume
      expansion during the wet oxidation. Following wet removal of core Si by KOH
      yields the SiO2 micro- or nanotubes, either in test tube shape or in open shape
      at both ends, depending on processing method. The vertical arrays of the SiO2
      tube on the Si substrate, after hydrophobic siloxane oligomer printing, has been
      found to have very large loading capacity on water, due to extremely high
      porosity (>90%) and good enough mechanical stability. The novel method to
      fabricate SiO2 tubes can shed new light in design of novel aquatic devices, other
      than simple mimicking the leg of a water strider. Also, the method may be very
      helpful in various applications of SiO2 nanotubes. 

PMID- 24313458
TI  - From solution to the gas phase: stepwise dehydration and kinetic trapping of
      substance P reveals the origin of peptide conformations.
AB  - Past experimental results and molecular dynamics simulations provide evidence
      that, under some conditions, electrospray ionization (ESI) of biomolecules
      produces ions that retain elements of solution phase structures. However, there
      is a dearth of information regarding the question raised by Breuker and
      McLafferty, "for how long, under what conditions, and to what extent, can
      solution structure be retained without solvent?" (Proc. Natl. Acad. Sci. U.S.A.
      2008, 105, 18145). Here, we use cryogenic ion mobility-mass spectrometry to
      experimentally probe the structural evolution of the undecapeptide substance P
      (SP) during the final stages of ESI. The results reveal that anhydrous SP
      conformers originate from evaporation of cluster ions, specifically, [SP +
      2H](2+) (H2O)n (n = 0 to ~50) and [SP + 3H](3+) (H2O)n (n = 0 to ~30), and that
      major structural changes do not occur during the evaporative process. In the case
      of [SP + 3H](3+), the results demonstrate that a compact dehydrated conformer
      population can be kinetically trapped on the time scale of several milliseconds,
      even when an extended gas phase conformation is energetically favorable. 

PMID- 24313461
TI  - Effects of implant drill wear, irrigation, and drill materials on heat generation
      in osteotomy sites.
AB  - This study evaluated the effects of drill wear on bone temperature during
      osteotomy preparation with 3 types of drills and compared heat production between
      drills. The drills used in this study were titanium nitride-coated metal,
      tungsten carbide carbon-coated metal, and zirconia ceramic drills. An osteotomy
      11 mm in depth was formed in bovine scapular bone following the manufacturer's
      recommended drill sequences. Drilling was performed without irrigation and
      repeated 20 times; temperature was measured every 5 times. Next, 200 rounds of
      drilling during irrigation were performed for each drill, with temperature change
      monitored until round 200. Analysis of variance statistics were used for analyses
      of the measured data. Drilling without irrigation showed significant thermal
      increase at all time points compared to drilling with irrigation (P < .001). No
      significant difference was found between drill materials. Under irrigation, the
      frequency of previous drilling had minimal effects on thermal change. The
      repeated-measures analysis of variance revealed major thermal change at the
      initial time point (P < .0001), and the multiple comparison tests revealed a
      significant difference in temperature between the initial drills that had been
      used 50 or fewer times and those that had been used more than 50 times,
      irrespective of the drill material. The results of this study indicate that the
      initial drill should be changed in osteotomy preparation with irrigation after
      they have been used 50 times. Irrigation may be a more critical factor for the
      control of temperature elevation than is the drill material. 

PMID- 24313460
TI  - British Dietetic Association evidence-based guidelines for the dietary management
      of Crohn's disease in adults.
AB  - BACKGROUND: Crohn's disease is a debilitating chronic inflammatory bowel disease.
      Appropriate use of diet and nutritional therapy is integral to the overall
      management strategy of Crohn's disease. The aim was to develop evidence-based
      guidelines on the dietary management of Crohn's disease in adults. METHODS:
      Questions relating to the dietary management of Crohn's disease were developed.
      These included the roles of enteral nutrition to induce remission, food re
      introduction diets to structure food re-introduction and maintain remission, and
      dietary management of stricturing disease, as well as whether probiotics or
      prebiotics induce or maintain remission. A comprehensive literature search was
      conducted and relevant studies from January 1985 to November 2009 were identified
      using the electronic database search engines CINAHL, Cochrane Library, EMBASE,
      MEDLINE, Scopus and Web of Science. Evidence statements, recommendations,
      practical considerations and research recommendations were developed. RESULTS:
      Fifteen research papers were critically appraised and the evidence formed the
      basis of these guidelines. Although corticosteroids appear to be more effective,
      enteral nutrition (elemental or non-elemental) can be offered as an alternative
      option to induce disease remission. After a course of enteral nutrition, food re
      introduction diets may be useful to structure food re-introduction and help
      maintain disease remission. Dietary fibre is contraindicated in the presence of
      strictures as a result of the risk of mechanical obstruction. The use of
      probiotics and prebiotics is not currently supported. CONCLUSIONS: As an
      alternative to corticosteroids, evidence supports enteral nutrition to induce
      disease remission. Food re-introduction diets provide structure to food re
      introduction and help maintain disease remission. These guidelines aim to reduce
      variation in clinical practice.

PMID- 24313462
TI  - Phototherapy, psoriasis, and the age of biologics.
AB  - Over 10 years have passed since the first approval of a biologic agent for the
      treatment of psoriasis. No one can argue that the arrival of this entirely new,
      highly effective class of medications has not forever changed the therapeutic
      landscape for psoriasis. Traditional treatments such as phototherapy, however,
      remain both viable and effective therapies, both as standalone treatments and in
      combination with biologics. In general, synergistic effects are noted for
      combinations utilizing phototherapy; however, the long-term impact of these
      combinations on skin cancer development has yet to be fully determined.
      Increasing financial pressures for cost-effective therapies augment the appeal of
      phototherapy and other traditional treatments as compared with the more costly
      biologics. Phototherapy also remains strong outside the realm of psoriasis, in
      the management of atopic dermatitis, vitiligo, and cutaneous T-cell lymphoma,
      among other conditions. Phototherapy will remain a cornerstone in the management
      of psoriasis as well as nonpsoriatic skin conditions, as its efficacy is well
      known, its financial cost is reasonable, it is readily compatible with other
      therapeutics, and its utility is historically proven. 

PMID- 24313463
TI  - Deferasirox improves hematologic and hepatic function with effective reduction of
      serum ferritin and liver iron concentration in transfusional iron overload
      patients with myelodysplastic syndrome or aplastic anemia.
AB  - BACKGROUND: Transfusional iron overload and its consequences are challenges in
      chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic
      anemia (AA). STUDY DESIGN AND METHODS: This was a prospective, multicenter, open
      label study to investigate the efficacy of deferasirox (DFX) by serial
      measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC)
      level using relaxation rates magnetic resonance imaging, and other laboratory
      variables in patients with MDS or AA. RESULTS: A total of 96 patients showing S
      ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the
      end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366)
      and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg
      Fe/g dry weight from baseline. Hemoglobin level and platelet counts were
      significantly increased from baseline (p=0.002 and p=0.025, respectively) for
      patients showing significant anemia or thrombocytopenia. Elevated alanine
      aminotransferase was also significantly decreased from baseline. CONCLUSIONS:
      This study shows that DFX is effective in reducing S-ferritin and LIC level in
      transfusional iron overload patients with MDS or AA and is well tolerated. In
      addition, positive effects in hematologic and hepatic function can be expected
      with DFX. Iron chelation treatment should be considered in transfused patients
      with MDS and AA when transfusion-related iron overload is documented.

PMID- 24313464
TI  - Molecular identification of the economically important freshwater mussels
      (Mollusca-Bivalvia-Unionoida) of Thailand: developing species-specific markers
      from AFLPs.
AB  - Shells of certain freshwater mussel (Unionoida) species are highly demanded and
      serve as raw material for a range of decorative and pharmaceutical products. In
      Thailand, most animals for this purpose are currently harvested from wild
      populations, with unionoid culture still being in its infancy. Whilst reliable
      species identification is a prerequisite for developing a large-scale industry,
      identification by morphological means is hampered by extensive phenotypic
      plasticity and poor knowledge of species delimitations. To facilitate alternative
      molecular identification, we developed species-specific markers for the three
      Thai unionoids with considerable economic potential (CEP): that is, Chamberlainia
      hainesiana, Hyriopsis desowitzi and Hyriopsis myersiana. For this purpose,
      amplified fragment length polymorphism (AFLP) fingerprints using 24 specific
      primer pairs were generated for eight samples of each CEP species and four
      samples of the closely related, non-CEP species Contradens contradens. Cloning
      and sequencing of 13 CEP species-specific AFLP bands revealed fragment collision
      at three occasions. In total, 16 species-specific primer pairs were designed and
      tested on 92 Thai specimens spanning seven species and four genera. Thereby,
      specificity of (1) three primers to C. hainesiana, (2) one primer to H. desowitzi
      + Hyriopsis bialata, (3) one primer to H. myersiana + H. bialata and (4) four
      primers to all three Hyriopsis species tested was confirmed. Respective multiplex
      PCR protocols are provided. The developed primers enable cheap, quick and
      reliable identification of the Thai CEP species by one to three PCRs and offer a
      tool for a range of additional applications within mussel culture and ecological
      and evolutionary research on these important organisms. 

PMID- 24313465
TI  - Dynamic interplay between autophagic flux and Akt during melanoma progression in
      vitro.
AB  - Despite advances in cancer diagnosis and therapy, metastatic melanoma remains
      untreatable, due to its notorious resistance to apoptosis, deeming traditional
      therapies obsolete. Deregulated PI3K/Akt signalling is a common oncogenic event
      enabling melanocyte transformation and represents a significant and 'druggable'
      pathway in melanoma. Emerging data show that the ability of cancer cells to
      survive is also facilitated by alteration of vital homoeostatic mechanisms, such
      as autophagy. Although the role of autophagy in melanoma is still controversial,
      recent studies suggest that basal autophagy is down-modulated in primary
      melanomas. However, the dynamic connection between pro-tumorigenic PI3K/Akt and
      autophagy during melanoma progression has not been systematically studied. By
      using human primary melanocytes, incipient melanoma and metastatic melanoma cell
      lines, we show that early in melanomagenesis, increased Akt activity is
      associated with a low baseline autophagic flux. However, during melanoma
      progression, metastatic melanoma cells regain the ability to stimulate autophagic
      flux, supporting survival. Heightened autophagy is associated with an attenuated
      Akt activation status and can be suppressed by overexpressing a constitutive
      active mutant of Akt. On the other hand, blocking the higher Akt activity of
      primary melanoma is sufficient to incite autophagy. Interestingly, we found that
      although Akt supports survival of melanocytes and all melanoma cell lines,
      autophagy inhibition specifically targeted the metastatic melanoma cells, thus
      indicating a stage-specific requirement for Akt and autophagic flux, throughout
      melanoma progression. Therefore, this study highlights a dynamic interplay
      between Akt signalling and autophagic rescue in melanoma, which should be
      considered in the design of therapeutic strategies targeting these pathways. 

PMID- 24313466
TI  - Has Hajj-associated Middle East Respiratory Syndrome Coronavirus transmission
      occurred? The case for effective post-Hajj surveillance for infection.

PMID- 24313467
TI  - Uniqueness of the equation for quantum state vector collapse.
AB  - The linearity of quantum mechanics leads, under the assumption that the wave
      function offers a complete description of reality, to grotesque situations
      famously known as Schrodinger's cat. Ways out are either adding elements of
      reality or replacing the linear evolution by a nonlinear one. Models of
      spontaneous wave function collapses took the latter path. The way such models are
      constructed leaves the question of whether such models are in some sense unique,
      i.e., whether the nonlinear equations replacing Schrodinger's equation are
      uniquely determined as collapse equations. Various people worked on identifying
      the class of nonlinear modifications of the Schrodinger equation, compatible with
      general physical requirements. Here we identify the most general class of
      continuous wave function evolutions under the assumption of no-faster-than-light
      signaling. 

PMID- 24313468
TI  - Violation of the entanglement area law in bosonic systems with Bose surfaces:
      possible application to Bose metals.
AB  - We show the violation of the entanglement area law for bosonic systems with Bose
      surfaces. For bosonic systems with gapless factorized energy dispersions on an
      N(d) Cartesian lattice in d dimensions, e.g., the exciton Bose liquid in two
      dimensions, we explicitly show that a belt subsystem with width L preserving
      translational symmetry along d-1 Cartesian axes has leading entanglement entropy
      (N(d-1)/3)lnL. Using this result, the strong subadditivity inequality, and
      lattice symmetries, we bound the entanglement entropy of a rectangular subsystem
      from below and above showing a logarithmic violation of the area law. For
      subsystems with a single flat boundary, we also bound the entanglement entropy
      from below showing a logarithmic violation, and argue that the entanglement
      entropy of subsystems with arbitrary smooth boundaries are similarly bounded.

PMID- 24313469
TI  - Measurement-based quantum computation with trapped ions.
AB  - Measurement-based quantum computation represents a powerful and flexible
      framework for quantum information processing, based on the notion of entangled
      quantum states as computational resources. The most prominent application is the
      one-way quantum computer, with the cluster state as its universal resource. Here
      we demonstrate the principles of measurement-based quantum computation using
      deterministically generated cluster states, in a system of trapped calcium ions.
      First we implement a universal set of operations for quantum computing. Second we
      demonstrate a family of measurement-based quantum error correction codes and show
      their improved performance as the code length is increased. The methods presented
      can be directly scaled up to generate graph states of several tens of qubits. 

PMID- 24313470
TI  - Dynamics of a tagged monomer: effects of elastic pinning and harmonic absorption.
AB  - We study the dynamics of a tagged monomer of a Rouse polymer for different
      initial configurations. In the case of free evolution, the monomer displays
      subdiffusive behavior with strong memory of the initial state. In the presence of
      either elastic pinning or harmonic absorption, we show that the steady state is
      independent of the initial condition that, however, strongly affects the
      transient regime, resulting in nonmonotonic behavior and power-law relaxation
      with varying exponents. 

PMID- 24313471
TI  - AMS-02 results support the secondary origin of cosmic ray positrons.
AB  - We show that the recent AMS-02 positron fraction measurement is consistent with a
      secondary origin for positrons and does not require additional primary sources
      such as pulsars or dark matter. The measured positron fraction at high energy
      saturates the previously predicted upper bound for secondary production, obtained
      by neglecting radiative losses. This coincidence, which will be further tested by
      upcoming AMS-02 data at higher energy, is a compelling indication for a secondary
      source. Within the secondary model, the AMS-02 data imply a cosmic ray
      propagation time in the Galaxy of <10(6) yr and an average traversed interstellar
      matter density of ~1 cm(-3), comparable to the density of the Milky Way gaseous
      disk, at a rigidity of 300 GV.

PMID- 24313472
TI  - Imprints of superfluidity on magnetoelastic quasiperiodic oscillations of soft
      gamma-ray repeaters.
AB  - Our numerical simulations show that axisymmetric, torsional, magnetoelastic
      oscillations of magnetars with a superfluid core can explain the whole range of
      observed quasiperiodic oscillations (QPOs) in the giant flares of soft gamma-ray
      repeaters. There exist constant phase QPOs at f is < or approximately equal to
      150 Hz and resonantly excited high-frequency QPOs (f>500 Hz), in good agreement
      with observations. The range of magnetic field strengths required to match the
      observed QPO frequencies agrees with that from spin-down estimates. These results
      suggest that there is at least one superfluid species in magnetar cores.

PMID- 24313473
TI  - Tensile strength and the mining of black holes.
AB  - There are a number of important thought experiments that involve raising and
      lowering boxes full of radiation in the vicinity of black hole horizons. This
      Letter looks at the limitations placed on these thought experiments by the null
      energy condition, which imposes a fundamental bound on the tensile-strength-to
      weight ratio of the materials involved, makes it impossible to build a box near
      the horizon that is wider than a single wavelength of the Hawking quanta, and
      puts a severe constraint on the operation of "space elevators" near black holes.
      In particular, it is shown that proposals for mining black holes by lowering
      boxes near the horizon, collecting some Hawking radiation, and dragging it out to
      infinity cannot proceed nearly as rapidly as has previously been claimed. As a
      consequence of this limitation, the boxes and all the moving parts are
      superfluous and black holes can be destroyed equally rapidly by threading the
      horizon with strings. 

PMID- 24313474
TI  - Quantum integrability for three-point functions of maximally supersymmetric Yang
      Mills theory.
AB  - Quantum corrections to three-point functions of scalar single trace operators in
      planar N=4 Super-Yang-Mills theory are studied using integrability. At one loop,
      we find new algebraic structures that not only govern all two-loop corrections to
      the mixing of the operators but also automatically incorporate all one-loop
      diagrams correcting the tree-level Wick contractions. Speculations about possible
      extensions of our construction to all loop orders are given. We also match our
      results with the strong coupling predictions in the classical (Frolov-Tseytlin)
      limit. 

PMID- 24313475
TI  - Holographic dual of an Einstein-Podolsky-Rosen pair has a wormhole.
AB  - We construct the holographic dual of two colored quasiparticles in maximally
      supersymmetric Yang-Mills theory entangled in a color singlet Einstein-Podolsky
      Rosen (EPR) pair. In the holographic dual, the entanglement is encoded in a
      geometry of a nontraversable wormhole on the world sheet of the flux tube
      connecting the pair. This gives a simple example supporting the recent claim by
      Maldacena and Susskind that EPR pairs and nontraversable wormholes are equivalent
      descriptions of the same physics. 

PMID- 24313476
TI  - Holographic Schwinger effect and the geometry of entanglement.
AB  - We show that the recently proposed bulk dual of an entangled pair of a quark and
      an antiquark corresponds to the Lorentzian continuation of the tunneling
      instanton describing Schwinger pair creation in the dual field theory. This
      observation supports and further explains the claim by Jensen and Karch that the
      bulk dual of an Einstein-Podolsky-Rosen pair is a string with a wormhole on its
      world sheet. We suggest that this constitutes a holographically dual realization
      of the creation of a Wheeler wormhole. 

PMID- 24313477
TI  - Yukawa unification predictions with effective "mirage" mediation.
AB  - In this Letter we analyze the consequences, for the LHC, of gauge and third
      family Yukawa coupling unification with a particular set of boundary conditions
      defined at the grand unified theory (GUT) scale, which we characterize as
      effective "mirage" mediation. We perform a global chi2 analysis including the
      observables M(W), M(Z), G(F), alpha(em)(-1), alpha(s)(M(Z)), M(t), m(b)(m(b)),
      M(tau), BR(B->X(s)gamma), BR(B(s)->MU(+)MU(-)), and M(h). The fit is performed in
      the minimal supersymmetric standard model in terms of 10 GUT scale parameters,
      while tanbeta and MU are fixed at the weak scale. We find good fits to the low
      energy data and a supersymmetry spectrum which is dramatically different than
      previously studied in the context of Yukawa unification.

PMID- 24313478
TI  - Electroweak Higgs boson plus three jet production at next-to-leading-order QCD.
AB  - We calculate next-to-leading order (NLO) QCD corrections to electroweak Higgs
      boson plus three jet production. Both vector boson fusion (VBF) and Higgs
      strahlung type contributions are included along with all interferences. The
      calculation is implemented within the Matchbox NLO framework of the Herwig++
      event generator. 

PMID- 24313482
TI  - Collinear resonance ionization spectroscopy of neutron-deficient francium
      isotopes.
AB  - The magnetic moments and isotope shifts of the neutron-deficient francium
      isotopes (202-205)Fr were measured at ISOLDE-CERN with use of collinear resonance
      ionization spectroscopy. A production-to-detection efficiency of 1% was measured
      for (202)Fr. The background from nonresonant and collisional ionization was
      maintained below one ion in 10(5) beam particles. Through a comparison of the
      measured charge radii with predictions from the spherical droplet model, it is
      concluded that the ground-state wave function remains spherical down to (205)Fr,
      with a departure observed in (203)Fr (N=116).

PMID- 24313483
TI  - In-beam gamma-ray spectroscopy of ^34,36,38Mg: merging the N=20 and N=28 shell
      quenching.
AB  - Neutron-rich N=22, 24, 26 magnesium isotopes were studied via in-beam gamma-ray
      spectroscopy at the RIKEN Radioactive Isotope Beam Factory following secondary
      fragmentation reactions on a carbon target at ~200 MeV/nucleon. In the one- and
      two-proton removal channels from 39Al and 40Si beams, two distinct gamma-ray
      transitions were observed in 38Mg, while in the one-proton removal reaction from
      37Al a new transition was observed in addition to the known 2(1)(+)->0(g.s.)(+)
      decay. From the experimental systematics and comparison to theoretical
      predictions it is concluded that the transitions belong to the 2(1)(+)
      >0(g.s.)(+) and 4(1)(+)->2(1)(+) decays in 36Mg and 38Mg, respectively. For 34Mg,
      previously reported 2(1)(+) and 4(1)(+) level energies were remeasured. The
      deduced E(4(1)(+))/E(2(1)(+)) ratios for 34,36,38Mg of 3.14(5), 3.07(5), and
      3.07(5) are almost identical and suggest the emergence of a large area of
      deformation extending from the N=20 to the N=28 shell quenching.

PMID- 24313479
TI  - Measurement of neutrino oscillation parameters from muon neutrino disappearance
      with an off-axis beam.
AB  - The T2K Collaboration reports a precision measurement of muon neutrino
      disappearance with an off-axis neutrino beam with a peak energy of 0.6 GeV. Near
      detector measurements are used to constrain the neutrino flux and cross section
      parameters. The Super-Kamiokande far detector, which is 295 km downstream of the
      neutrino production target, collected data corresponding to 3.01*10(20) protons
      on target. In the absence of neutrino oscillations, 205+/-17 (syst) events are
      expected to be detected while only 58 muon neutrino event candidates are
      observed. A fit to the neutrino rate and energy spectrum, assuming three neutrino
      flavors and normal mass hierarchy yields a best-fit mixing angle
      sin2(theta23)=0.514+/-0.082 and mass splitting |Deltam(32)(2)|=2.44(
      0.15)(+0.17)*10(-3) eV2/c4. Our result corresponds to the maximal oscillation
      disappearance probability.

PMID- 24313484
TI  - Vibrational mode multiplexing of ultracold atoms.
AB  - Sending multiple messages on qubits encoded in different vibrational modes of
      cold atoms or ions along a transmission waveguide requires us to merge first and
      then separate the modes at input and output ends. Similarly, different qubits can
      be stored in the modes of a trap and be separated later. We design the fast
      splitting of a harmonic trap into an asymmetric double well so that the initial
      ground vibrational state becomes the ground state of one of two final wells, and
      the initial first excited state becomes the ground state of the other well. This
      might be done adiabatically by slowly deforming the trap. We speed up the process
      by inverse engineering a double-function trap using dynamical invariants. The
      separation (demultiplexing) followed by an inversion of the asymmetric bias and
      then by the reverse process (multiplexing) provides a population inversion
      protocol based solely on trap reshaping. 

PMID- 24313485
TI  - Experimental evidence on the mechanism of dissociative electron attachment to
      formic acid.
AB  - Two mechanisms for dissociative electron attachment in HCOOH, the formation of
      HCOO(-)+H, were proposed in the literature: (i) via a direct electron attachment
      into a sigma* resonance, augmented by dipole binding of the incident electron [G.
      A. Gallup et al., Phys. Rev. A 79, 042701 (2009)], and (ii) with the 1.8 eV pi*
      resonance as a doorway state, linked to the products by symmetry lowering
      distortion of the temporary anion, primarily the C-H bond, from the planar
      symmetry [T. N. Rescigno et al., Phys. Rev. Lett. 96, 213201 (2006)]. The later
      mechanism implies a reduction of the cross section upon deuteration of the
      hydrogen bonded to the C atom, whereas the former mechanism would leave the cross
      section unaffected. Our experimental absolute cross sections for the four
      isotopomers of formic acid show that deuteration on the C atom reduces the cross
      section value only marginally (by 12%) compared to deuteration on the O atom
      (reduction by a factor of 16), and thus favor mechanism (i).

PMID- 24313486
TI  - Quantum optical state comparison amplifier.
AB  - It is a fundamental principle of quantum theory that an unknown state cannot be
      copied or, as a consequence, an unknown optical signal cannot be amplified
      deterministically and perfectly. Here we describe a protocol that provides
      nondeterministic quantum optical amplification in the coherent state basis with
      high gain and high fidelity and which does not use quantum resources. The scheme
      is based on two mature quantum optical technologies: coherent state comparison
      and photon subtraction. The method compares favorably with all previous
      nondeterministic amplifiers in terms of fidelity and success probability. 

PMID- 24313487
TI  - Experimentally accessing the optimal temporal mode of traveling quantum light
      states.
AB  - The characterization or subsequent use of a propagating optical quantum state
      requires the knowledge of its precise temporal mode. Defining this mode structure
      very often relies on a detailed a priori knowledge of the used resources, when
      available, and can additionally call for an involved theoretical modeling. In
      contrast, here we report on a practical method enabling us to infer the optimal
      temporal mode directly from experimental data acquired via homodyne detection,
      without any assumptions on the state. The approach is based on a multimode
      analysis using eigenfunction expansion of the autocorrelation function. This
      capability is illustrated by experimental data from the preparation of Fock
      states and coherent state superposition.

PMID- 24313488
TI  - On-chip manipulation of single photons from a diamond defect.
AB  - Operating reconfigurable quantum circuits with single photon sources is a key
      goal of photonic quantum information science and technology. We use an integrated
      waveguide device containing directional couplers and a reconfigurable thermal
      phase controller to manipulate single photons emitted from a chromium related
      color center in diamond. Observation of both a wavelike interference pattern and
      particlelike sub-Poissionian autocorrelation functions demonstrates coherent
      manipulation of single photons emitted from the chromium related center and
      verifies wave particle duality. 

PMID- 24313489
TI  - Perfect surface wave cloaks.
AB  - This Letter presents a method for making an uneven surface behave as a flat
      surface. This allows an object to be concealed (cloaked) under an uneven portion
      of the surface, without disturbing the wave propagation on the surface. The
      cloaks proposed in this Letter achieve perfect cloaking that only relies upon
      isotropic radially dependent refractive index profiles, contrary to those
      previously published. In addition, these cloaks are very thin, just a fraction of
      a wavelength in thickness, yet can conceal electrically large objects. While this
      paper focuses on cloaking electromagnetic surface waves, the theory is also valid
      for other types of surface waves. The performance of these cloaks is simulated
      using dielectric filled waveguide geometries, and the curvature of the surface is
      shown to be rendered invisible, hiding any object positioned underneath. Finally,
      a transformation of the required dielectric slab permittivity was performed for
      surface wave propagation, demonstrating the practical applicability of this
      technique. 

PMID- 24313490
TI  - Photonic cavity synchronization of nanomechanical oscillators.
AB  - Synchronization in oscillatory systems is a frequent natural phenomenon and is
      becoming an important concept in modern physics. Nanomechanical resonators are
      ideal systems for studying synchronization due to their controllable oscillation
      properties and engineerable nonlinearities. Here we demonstrate synchronization
      of two nanomechanical oscillators via a photonic resonator, enabling
      optomechanical synchronization between mechanically isolated nanomechanical
      resonators. Optical backaction gives rise to both reactive and dissipative
      coupling of the mechanical resonators, leading to coherent oscillation and mutual
      locking of resonators with dynamics beyond the widely accepted phase oscillator
      (Kuramoto) model. In addition to the phase difference between the oscillators,
      also their amplitudes are coupled, resulting in the emergence of sidebands around
      the synchronized carrier signal. 

PMID- 24313491
TI  - Phase reduction method for strongly perturbed limit cycle oscillators.
AB  - The phase reduction method for limit cycle oscillators subjected to weak
      perturbations has significantly contributed to theoretical investigations of
      rhythmic phenomena. We here propose a generalized phase reduction method that is
      also applicable to strongly perturbed limit cycle oscillators. The fundamental
      assumption of our method is that the perturbations can be decomposed into a
      slowly varying component as compared to the amplitude relaxation time and
      remaining weak fluctuations. Under this assumption, we introduce a generalized
      phase parameterized by the slowly varying component and derive a closed equation
      for the generalized phase describing the oscillator dynamics. The proposed method
      enables us to explore a broader class of rhythmic phenomena, in which the shape
      and frequency of the oscillation may vary largely because of the perturbations.
      We illustrate our method by analyzing the synchronization dynamics of limit cycle
      oscillators driven by strong periodic signals. It is shown that the proposed
      method accurately predicts the synchronization properties of the oscillators,
      while the conventional method does not. 

PMID- 24313492
TI  - Kondo signature in heat transfer via a local two-state system.
AB  - We study the Kondo effect in heat transport via a local two-state system. This
      system is described by the spin-boson Hamiltonian with Ohmic dissipation, which
      can be mapped onto the Kondo model with anisotropic exchange coupling. We
      calculate thermal conductance by the Monte Carlo method based on the exact
      formula. Thermal conductance has a scaling form
      kappa=(k(B)(2)T(K)/h)f(alpha,T/T(K)), where T(K) and alpha indicate the Kondo
      temperature and dimensionless coupling strength, respectively. Temperature
      dependence of conductance is classified by the Kondo temperature as kappa is
      proportional to (T/T(K))(3) for T<<T(K) and kappa is proportional to
      (kB)T/homega(c))(2alpha-1) for T>>T(K). Similarities to the Kondo signature in
      electric transport are discussed.

PMID- 24313494
TI  - Molecular dynamics simulations of classical stopping power.
AB  - Molecular dynamics can provide very accurate tests of classical kinetic theory;
      for example, unambiguous comparisons can be made for classical particles
      interacting via a repulsive 1/r potential. The plasma stopping power problem, of
      great interest in its own right, provides an especially stringent test of a
      velocity-dependent transport property. We have performed large-scale (~10(4)
      10(6) particles) molecular dynamics simulations of charged-particle stopping in a
      classical electron gas that span the weak to moderately strong intratarget
      coupling regimes. Projectile-target coupling is varied with projectile charge and
      velocity. Comparisons are made with disparate kinetic theories (both Boltzmann
      and Lenard-Balescu classes) and fully convergent theories to establish regimes of
      validity. We extend these various stopping models to improve agreement with the
      MD data and provide a useful fit to our results.

PMID- 24313495
TI  - Electron acceleration in a nonrelativistic shock with very high Alfven Mach
      number.
AB  - Electron acceleration associated with various plasma kinetic instabilities in a
      nonrelativistic shock with very high Alfven Mach number (M(A)~45) is revealed by
      means of a two-dimensional fully kinetic particle-in-cell simulation.
      Electromagnetic (ion Weibel) and electrostatic (ion-acoustic and Buneman)
      instabilities are strongly activated at the same time in different regions of the
      two-dimensional shock structure. Relativistic electrons are quickly produced
      predominantly by the shock surfing mechanism with the Buneman instability at the
      leading edge of the foot. The energy spectrum has a high-energy tail exceeding
      the upstream ion kinetic energy accompanying the main thermal population. This
      gives a favorable condition for the ion-acoustic instability at the shock front,
      which in turn results in additional energization. The large-amplitude ion Weibel
      instability generates current sheets in the foot, implying another dissipation
      mechanism via magnetic reconnection in a three-dimensional shock structure in the
      very-high-M(A) regime.

PMID- 24313493
TI  - Performance of high-convergence, layered DT implosions with extended-duration
      pulses at the National Ignition Facility.
AB  - Radiation-driven, low-adiabat, cryogenic DT layered plastic capsule implosions
      were carried out on the National Ignition Facility (NIF) to study the sensitivity
      of performance to peak power and drive duration. An implosion with extended drive
      and at reduced peak power of 350 TW achieved the highest compression with fuel
      areal density of ~1.3+/-0.1 g/cm2, representing a significant step from
      previously measured ~1.0 g/cm2 toward a goal of 1.5 g/cm2. Future experiments
      will focus on understanding and mitigating hydrodynamic instabilities and mix,
      and improving symmetry required to reach the threshold for thermonuclear ignition
      on NIF.

PMID- 24313496
TI  - Quantum rotor model for a Bose-Einstein condensate of dipolar molecules.
AB  - We show that a Bose-Einstein condensate of heteronuclear molecules in the regime
      of small and static electric fields is described by a quantum rotor model for the
      macroscopic electric dipole moment of the molecular gas cloud. We solve this
      model exactly and find the symmetric, i.e., rotationally invariant, and dipolar
      phases expected from the single-molecule problem, but also an axial and planar
      nematic phase due to many-body effects. Investigation of the wave function of the
      macroscopic dipole moment also reveals squeezing of the probability distribution
      for the angular momentum of the molecules. 

PMID- 24313497
TI  - Tunneling-induced restoration of the degeneracy and the time-reversal symmetry
      breaking in optical lattices.
AB  - We study the ground-state properties of bosons loaded into the p band of a one
      dimensional optical lattice. We show that the phase diagram of the system is
      substantially affected by the anharmonicity of the lattice potential. In
      particular, for a certain range of tunneling strength, the full many-body ground
      state of the system becomes degenerate. In this region, an additional symmetry of
      the system, namely, the parity of the occupation number of the chosen orbital, is
      spontaneously broken. The state with a nonvanishing staggered angular momentum,
      which breaks the time-reversal symmetry, becomes the true ground state of the
      system. 

PMID- 24313498
TI  - NMR signature of one-dimensional behavior of 3He in nanopores.
AB  - We have performed thermodynamic and NMR relaxation time measurements of 3He
      adsorbed in the pores of the mesoporous molecular sieve MCM-41 at temperatures
      down to 1.7 K and at a range of frequencies up to 240 kHz. The MCM-41 substrate
      comprises a uniform array of quasi-1D straight pores with a diameter of 2.3 nm.
      We preplated the pores with a monolayer of 4He to achieve an effective diameter
      of 1.6 nm at low temperatures. We made NMR measurements as a function of line
      density and frequency to investigate the spin dynamics and the effect of
      dimensionality. We observed T(1) is proportional to omega1/2, which is
      characteristic of one-dimensional diffusion. At these temperatures this arises
      from a classical size effect in the narrow pores. Our results demonstrate the
      possibility to study the spin dynamics of a 1D Tomonaga-Luttinger liquid at lower
      temperatures, where the 3He liquid will constitute a quantum 1D system.

PMID- 24313481
TI  - Quadrupole anisotropy in dihadron azimuthal correlations in central d+Au
      collisions at ?(s(NN))=200 GeV.
AB  - The PHENIX collaboration at the Relativistic Heavy Ion Collider (RHIC) reports
      measurements of azimuthal dihadron correlations near midrapidity in d+Au
      collisions at ?(s(NN))=200 GeV. These measurements complement recent analyses by
      experiments at the Large Hadron Collider (LHC) involving central p+Pb collisions
      at ?(s(NN))=5.02 TeV, which have indicated strong anisotropic long-range
      correlations in angular distributions of hadron pairs. The origin of these
      anisotropies is currently unknown. Various competing explanations include parton
      saturation and hydrodynamic flow. We observe qualitatively similar, but larger,
      anisotropies in d+Au collisions at RHIC compared to those seen in p+Pb collisions
      at the LHC. The larger extracted v2 values in d+Au are consistent with
      expectations from hydrodynamic calculations owing to the larger expected initial
      state eccentricity compared with that from p+Pb collisions. When both are divided
      by an estimate of the initial-state eccentricity the scaled anisotropies follow a
      common trend with multiplicity that may extend to heavy ion data at RHIC and the
      LHC, where the anisotropies are widely thought to arise from hydrodynamic flow.

PMID- 24313499
TI  - Realizing a Kondo-correlated state with ultracold atoms.
AB  - We propose a novel realization of Kondo physics with ultracold atomic gases. It
      is based on a Fermi sea of two different hyperfine states of one atom species
      forming bound states with a different species, which is spatially confined in a
      trapping potential. We show that different situations displaying Kondo physics
      can be realized when Feshbach resonances between the species are tuned by a
      magnetic field and the trapping frequency is varied. We illustrate that a mixture
      of 40K and 23Na atoms can be used to generate a Kondo-correlated state and that
      momentum resolved radio frequency spectroscopy can provide unambiguous signatures
      of the formation of Kondo resonances at the Fermi energy. We discuss how tools of
      atomic physics can be used to investigate open questions for Kondo physics, such
      as the extension of the Kondo screening cloud.

PMID- 24313500
TI  - Kinetic constraints, hierarchical relaxation, and onset of glassiness in strongly
      interacting and dissipative Rydberg gases.
AB  - We show that the dynamics of a laser driven Rydberg gas in the limit of strong
      dephasing is described by a master equation with manifest kinetic constraints.
      The equilibrium state of the system is uncorrelated but the constraints in the
      dynamics lead to spatially correlated collective relaxation reminiscent of
      glasses. We study and quantify the evolution towards equilibrium in one and two
      dimensions, and analyze how the degree of glassiness and the relaxation time are
      controlled by the interaction strength between Rydberg atoms. We also find that
      spontaneous decay of Rydberg excitations leads to an interruption of glassy
      relaxation that takes the system to a highly correlated nonequilibrium stationary
      state. The results presented here, which are in principle also applicable to
      other systems such as polar molecules and atoms with large magnetic dipole
      moments, show that the collective behavior of cold atomic and molecular ensembles
      can be similar to that found in soft condensed-matter systems. 

PMID- 24313502
TI  - Time-dependent relaxation of strained silicon-on-insulator lines using a
      partially coherent x-ray nanobeam.
AB  - We report on the quantitative determination of the strain map in a strained
      silicon-on-insulator line with a 200*70 nm2 cross section. In order to study a
      single line as a function of time, we used an x-ray nanobeam with relaxed
      coherence properties as a compromise between beam size, coherence, and intensity.
      We demonstrate how it is possible to refine the line deformation map at the
      nanoscale, and follow its evolution as the line relaxes under the influence of
      the x-ray nanobeam. We find that the strained line flattens itself under
      irradiation but maintains the same linear strain (epsilon(zz) unchanged).

PMID- 24313501
TI  - Chemically resolved interface structure of epitaxial graphene on SiC(0001).
AB  - Atomic-layer 2D crystals have unique properties that can be significantly
      modified through interaction with an underlying support. For epitaxial graphene
      on SiC(0001), the interface strongly influences the electronic properties of the
      overlaying graphene. We demonstrate a novel combination of x-ray scattering and
      spectroscopy for studying the complexities of such a buried interface structure.
      This approach employs x-ray standing wave-excited photoelectron spectroscopy in
      conjunction with x-ray reflectivity to produce a highly resolved chemically
      sensitive atomic profile for the terminal substrate bilayers, interface, and
      graphene layers along the SiC[0001] direction. 

PMID- 24313503
TI  - High-pressure synthesis and characterization of iridium trihydride.
AB  - We have performed in situ synchrotron x-ray diffraction studies of the iridium
      hydrogen system up to 125 GPa. At 55 GPa, a phase transition in the metal lattice
      from the fcc to a distorted simple cubic phase is observed. The new phase is
      characterized by a drastically increased volume per metal atom, indicating the
      formation of a metal hydride, and substantially decreased bulk modulus of 190 GPa
      (383 GPa for pure Ir). Ab initio calculations show that the hydrogen atoms occupy
      the face-centered positions in the metal matrix, making this the first known
      noninterstitial noble metal hydride and, with a stoichiometry of IrH(3), the one
      with the highest volumetric hydrogen content. Computations also reveal that
      several energetically competing phases exist, which can all be seen as having
      distorted simple cubic lattices. Slow kinetics during decomposition at pressures
      as low as 6 GPa suggest that this material is metastable at ambient pressure and
      low temperatures.

PMID- 24313504
TI  - Tuning plasmonic cloaks with an external magnetic field.
AB  - We propose a mechanism to actively tune the operation of plasmonic cloaks with an
      external magnetic field by investigating electromagnetic scattering by a
      dielectric cylinder coated with a magneto-optical shell. In the long wavelength
      limit, we show that the presence of a magnetic field may drastically reduce the
      scattering cross section at all observation angles. We demonstrate that the
      application of magnetic fields can modify the operation wavelength without the
      need of changing material and/or geometrical parameters. We also show that
      applied magnetic fields can reversibly switch on and off the cloak operation.
      These results, which could be achieved for existing magneto-optical materials,
      are shown to be robust to material losses, so that they may pave the way for
      developing actively tunable, versatile plasmonic cloaks. 

PMID- 24313505
TI  - Effect of surface elasticity on the rheology of nanometric liquids.
AB  - The rheological properties of liquids confined to nanometer scales are important
      in many physical situations. In this Letter, we demonstrate that the long-range
      elastic deformation of the confining surfaces must be taken into account when
      considering the rheology of nanometric liquids. In the case of a squeeze-flow
      geometry, we show that below a critical distance D(c), the liquid is clamped by
      its viscosity and its intrinsic properties cannot be disentangled from the global
      system response. Using nanorheology experiments, we demonstrate that picometer
      elastic deflections of the rigid confining surfaces dominate the overall
      mechanical response of nanometric liquids confined between solid walls.

PMID- 24313506
TI  - Tip-enhanced Raman investigation of extremely localized semiconductor-to-metal
      transition of a carbon nanotube.
AB  - The electronic properties of single walled carbon nanotubes (SWNTs) can change
      with a slight deformation, such as the one caused by the pressure of one SWNT
      crossing over the other in an "X" shape. The effect, however, is extremely
      localized. We present a tip-enhanced Raman investigation of the extremely
      localized semiconductor-to-metal transition of SWNTs in such a situation, where
      we can see how the Fano interaction, which is a Raman signature of metallic
      behavior, grows towards the junction and is localized within a few nanometers of
      its vicinity. After exploring the deconvoluted components of the G-band Raman
      mode, we were able to reveal the change in electronic properties of a SWNT at
      extremely high spatial resolution along its length. 

PMID- 24313507
TI  - Dirac cone with helical spin polarization in ultrathin alpha-Sn(001) films.
AB  - Spin-split two-dimensional electronic states have been observed on ultrathin
      Sn(001) films grown on InSb(001) substrates. Angle-resolved photoelectron
      spectroscopy (ARPES) performed on these films revealed Dirac-cone-like linear
      dispersion around the Gamma- point of the surface Brillouin zone, suggesting
      nearly massless electrons belonging to 2D surface states. The states disperse
      across a band gap between bulklike quantum well states in the films. Moreover,
      both circular dichroism of ARPES and spin-resolved ARPES studies show helical
      spin polarization of the Dirac-cone-like surface states, suggesting a
      topologically protected character as in a bulk topological insulator (TI). These
      results indicate that a quasi-3D TI phase can be realized in ultrathin films of
      zero-gap semiconductors.

PMID- 24313508
TI  - Polarity-driven surface metallicity in SmB6.
AB  - By a combined angle-resolved photoemission spectroscopy and density functional
      theory study, we discover that the surface metallicity is polarity driven in
      SmB6. Two surface states, not accounted for by the bulk band structure, are
      reproduced by slab calculations for coexisting B6 and Sm surface terminations.
      Our analysis reveals that a metallic surface state stems from an unusual
      property, generic to the (001) termination of all hexaborides: the presence of
      boron 2p dangling bonds, on a polar surface. The discovery of polarity-driven
      surface metallicity sheds new light on the 40-year old conundrum of the low
      temperature residual conductivity of SmB6, and raises a fundamental question in
      the field of topological Kondo insulators regarding the interplay between
      polarity and nontrivial topological properties.

PMID- 24313509
TI  - Chirality from interfacial spin-orbit coupling effects in magnetic bilayers.
AB  - As nanomagnetic devices scale to smaller sizes, spin-orbit coupling due to the
      broken structural inversion symmetry at interfaces becomes increasingly
      important. Here, we study interfacial spin-orbit coupling effects in magnetic
      bilayers using a simple Rashba model. The spin-orbit coupling introduces
      chirality into the behavior of the electrons and through them into the energetics
      of the magnetization. In the derived form of the magnetization dynamics, all of
      the contributions that are linear in the spin-orbit coupling follow from this
      chirality, considerably simplifying the analysis. For these systems, an important
      consequence is a correlation between the Dzyaloshinskii-Moriya interaction and
      the spin-orbit torque. We use this correlation to analyze recent experiments. 

PMID- 24313510
TI  - Tunable Anderson localization in hydrogenated graphene based on the electric
      field effect.
AB  - Effective control of hydrogenation of graphene is of great scientific and
      technological importance. However, the reversible control of H density (n(H)) on
      graphene is difficult due to the irreversible H2 formation of the detached H
      adatoms. Here we present a novel mechanism for controlling n(H) by using the
      unique proton transfer reaction between NH3 gas and hydrogenated graphene, which
      can be tuned by applying perpendicular electric fields. Using first-principles
      calculations, we show that n(H) can be reversibly tuned by the applied electric
      fields around the critical density for the Anderson localization in hydrogenated
      graphene. The proposed field-induced control of H adsorption or desorption on
      graphene opens a path toward the development of new graphene transistors based on
      the tunable degree of disorder.

PMID- 24313511
TI  - Fixing the energy scale in scanning tunneling microscopy on semiconductor
      surfaces.
AB  - In scanning tunneling experiments on semiconductor surfaces, the energy scale
      within the tunneling junction is usually unknown due to tip-induced band bending.
      Here, we experimentally recover the zero point of the energy scale by combining
      scanning tunneling microscopy with Kelvin probe force spectroscopy. With this
      technique, we revisit shallow acceptors buried in GaAs. Enhanced acceptor-related
      conductance is observed in negative, zero, and positive band-bending regimes. An
      Anderson-Hubbard model is used to rationalize our findings, capturing the
      crossover between the acceptor state being part of an impurity band for zero band
      bending and the acceptor state being split off and localized for strong negative
      or positive band bending, respectively. 

PMID- 24313512
TI  - Electrically tunable anomalous Hall effect in Pt thin films.
AB  - Pt is often considered to be an exchange-enhanced paramagnetic material, in which
      the Stoner criterion for ferromagnetism is nearly satisfied and, thus, external
      stimuli may induce unconventional magnetic characteristics. We report that a
      nonmagnetic perturbation in the form of a gate voltage applied via an ionic
      liquid induces an anomalous Hall effect (AHE) in Pt thin films, which resembles
      the AHE induced by the contact to Bi-doped yttrium iron garnet. Analysis of
      detailed temperature and magnetic field experiments indicates that the evolution
      of the AHE with temperature can be explained in terms of large local moments; the
      applied electric field induces magnetic moments as large as ~10 MU(B) that follow
      the Langevin function.

PMID- 24313513
TI  - Probing water structures in nanopores using tunneling currents.
AB  - We study the effect of volumetric constraints on the structure and electronic
      transport properties of distilled water in a nanopore with embedded electrodes.
      Combining classical molecular dynamics simulations with quantum scattering
      theory, we show that the structural motifs water exhibits inside the pore can be
      probed directly by tunneling. In particular, we show that the current does not
      follow a simple exponential curve at a critical pore diameter of about 8 A,
      rather it is larger than the one expected from simple tunneling through a
      barrier. This is due to a structural transition from bulklike to "nanodroplet"
      water domains. Our results can be tested with present experimental capabilities
      to develop our understanding of water as a complex medium at nanometer length
      scales.

PMID- 24313514
TI  - Optical spectrum of MoS2: many-body effects and diversity of exciton states.
AB  - We present first-principles calculations of the optical response of monolayer
      molybdenum disulfide employing the GW-Bethe-Salpeter equation (GW-BSE) approach
      including self-energy, excitonic, and electron-phonon effects. We show that
      monolayer MoS2 possesses a large and diverse number of strongly bound excitonic
      states with novel k-space characteristics that were not previously seen
      experimentally or theoretically. The absorption spectrum is shown to be dominated
      by excitonic states with a binding energy close to 1 eV and by strong electron
      phonon broadening in the visible to ultraviolet range. Our results explain recent
      experimental measurements and resolve inconsistencies between previous GW-BSE
      calculations.

PMID- 24313515
TI  - Kinks in the sigma band of graphene induced by electron-phonon coupling.
AB  - Angle-resolved photoemission spectroscopy reveals pronounced kinks in the
      dispersion of the sigma band of graphene. Such kinks are usually caused by the
      combination of a strong electron-boson interaction and the cutoff in the Fermi
      Dirac distribution. They are therefore not expected for the sigma band of
      graphene that has a binding energy of more than ~3.5 eV. We argue that the
      observed kinks are indeed caused by the electron-phonon interaction, but the role
      of the Fermi-Dirac distribution cutoff is assumed by a cutoff in the density of
      sigma states. The existence of the effect suggests a very weak coupling of holes
      in the sigma band not only to the pi electrons of graphene but also to the
      substrate electronic states. This is confirmed by the presence of such kinks for
      graphene on several different substrates that all show a strong coupling constant
      of lambda~1.

PMID- 24313516
TI  - Clock-controlled emission of single-electron wave packets in a solid-state
      circuit.
AB  - We demonstrate the energy- and time-resolved detection of single-electron wave
      packets from a clock-controlled source transmitted through a high-energy quantum
      Hall edge channel. A quantum dot source is loaded with single electrons which are
      then emitted ~150 meV above the Fermi energy. The energy spectroscopy of emitted
      electrons indicates that at high magnetic field these electrons can be
      transported over several microns without inelastic electron-electron or electron
      phonon scattering. Using a time-resolved spectroscopic technique, we deduce the
      wave packet size at picosecond resolution. We also show how this technique can be
      used to switch individual electrons into different electron waveguides (edge
      channels).

PMID- 24313518
TI  - Nature of the bad metallic behavior of Fe1.06Te inferred from its evolution in
      the magnetic state.
AB  - We investigate with angle-resolved photoelectron spectroscopy the changes of the
      Fermi surface and the main bands from the paramagnetic state to the
      antiferromagnetic (AFM) state occurring below 72 K in Fe1.06Te. The evolution is
      completely different from that observed in Fe pnictides, as nesting is absent.
      The AFM state is a rather good metal, in agreement with our magnetic band
      structure calculation. On the other hand, the paramagnetic state is very
      anomalous with a large pseudogap of ~65 meV on the electron pocket that closes in
      the AFM state. We discuss this behavior in connection with spin fluctuations
      existing above the magnetic transition and the correlations predicted in the spin
      freezing regime of the incoherent metallic state.

PMID- 24313517
TI  - Existence of orbital order and its fluctuation in superconducting Ba(Fe(1
      x)Co(x))2As2 single crystals revealed by x-ray absorption spectroscopy.
AB  - We performed temperature dependent x-ray linear dichroism (XLD) experiments on an
      iron pnictide system, Ba(Fe(1-x)Co(x))2As2 with x=0.00, 0.05, 0.08, and 0.10 to
      experimentally verify the existence of orbital ordering (OO). Substantial XLD was
      observed in polarization dependent x-ray absorption spectra of Fe L edges. By
      exploiting the difference in the temperature dependent behaviors, OO, and
      structure contributions to XLD could be clearly separated. The observed OO signal
      indicates different occupation numbers for d(yz) and d(zx) orbitals and supports
      the existence of ferro-OO. The results are also consistent with the theoretical
      prediction. Moreover, we find substantial OO signal well above the structural and
      magnetic transition temperatures, which suggests the existence of strong OO
      fluctuations up to high temperatures.

PMID- 24313519
TI  - Tetrahedral and orbital pairing: a fully gapped pairing scenario for the iron
      based superconductors.
AB  - Motivated by the fully gapped superconductivity in iron-based superconductors
      with uncompensated electron pockets, we propose a spin singlet, but orbital
      triplet analogue of the superfluid phase of ^{3}He-B. We show that orbital
      triplets with a nominal d-wave symmetry at the iron sites can transform as s-wave
      pairs under rotations about the selenium sites. Linear combinations of such d(xy)
      and d(x2-y(2)) triplets form a fully gapped, topological superconductor. Raman
      active excitations are predicted to develop below the superconducting transition
      temperature.

PMID- 24313520
TI  - Emergent honeycomb lattice in LiZn2Mo3O8.
AB  - We introduce the idea of emergent lattices, where a simple lattice decouples into
      two weakly coupled lattices as a way to stabilize spin liquids. In LiZn2Mo3O8,
      the disappearance of 2/3 of the spins at low temperatures suggests that its
      triangular lattice decouples into an emergent honeycomb lattice weakly coupled to
      the remaining spins, and we suggest several ways to test this proposal. We show
      that these orphan spins act to stabilize the spin liquid in the J1-J2 honeycomb
      model and also discuss a possible 3D analogue, Ba2MoYO6 that may form a "depleted
      fcc lattice."

PMID- 24313521
TI  - Exchange bias driven by Dzyaloshinskii-Moriya interactions.
AB  - The exchange bias effect in a compensated IrMn3/Co(111) system is studied using
      multiscale modeling from ab initio to atomistic spin model calculations. We
      evaluate numerically the out-of-plane hysteresis loops of the bilayer for
      different thicknesses of the ferromagnetic layer. The results show the existence
      of a perpendicular exchange bias and an enhancement of the coercivity of the
      system. To identify the origin of the exchange bias, we analyze the hysteresis
      loops of a selected bilayer by tuning the different contributions to the exchange
      interaction across the interface. Our results indicate that the exchange bias is
      primarily induced by Dzyaloshinskii-Moriya interactions, while the coercivity is
      increased mainly due to a spin-flop mechanism.

PMID- 24313522
TI  - Domain wall tilting in the presence of the Dzyaloshinskii-Moriya interaction in
      out-of-plane magnetized magnetic nanotracks.
AB  - We show that the Dzyaloshinskii-Moriya interaction (DMI) can lead to a tilting of
      the domain wall (DW) surface in perpendicularly magnetized magnetic nanotracks
      when DW dynamics are driven by an easy axis magnetic field or a spin polarized
      current. The DW tilting affects the DW dynamics for large DMI, and the tilting
      relaxation time can be very large as it scales with the square of the track
      width. The results are well explained by an extended collective coordinate model
      where DMI and DW tilting are included. We propose a simple way to estimate the
      DMI in magnetic multilayers by measuring the dependence of the DW tilt angle on a
      transverse static magnetic field. These results shed light on the current induced
      DW tilting observed recently in Co/Ni multilayers with structural inversion
      asymmetry. 

PMID- 24313523
TI  - Detection of microwave spin pumping using the inverse spin Hall effect.
AB  - We report on the electrical detection of the dynamical part of the spin-pumping
      current emitted during ferromagnetic resonance using inverse spin Hall effect
      methods. The experiment is performed on a YIG|Pt bilayer. The choice of yttrium
      iron garnet (YIG), a magnetic insulator, ensures that no charge current flows
      between the two layers and only the pure spin current produced by the
      magnetization dynamics is transferred into the adjacent strong spin-orbit Pt
      layer via spin pumping. To avoid measuring the parasitic eddy currents induced at
      the frequency of the microwave source, a resonance at half the frequency is
      induced using parametric excitation in the parallel geometry. Triggering this
      nonlinear effect allows us to directly detect on a spectrum analyzer the
      microwave component of the inverse spin Hall effect voltage. Signals as large as
      30 MUV are measured for precession angles of a couple of degrees. This direct
      detection provides a novel efficient means to study magnetization dynamics on a
      very wide frequency range with great sensitivity.

PMID- 24313524
TI  - Field-driven dynamics of correlated electrons in LiH and NaBH4 revealed by
      femtosecond x-ray diffraction.
AB  - We study the quasi-instantaneous change of electron density in the unit cells of
      LiH and NaBH4 in response to a nonresonant strong optical field. We determine for
      the first time the related transient electron density maps, applying femtosecond
      x-ray powder diffraction as a structure probe. The light-induced charge
      relocation in NaBH4 exhibits an electron transfer from the anion (BH(4)(-)) to
      the Na(+) cation. In contrast, LiH displays the opposite behavior, i.e., an
      increase of the ionicity of LiH in the presence of the strong electric field.
      This behavior originates from strong electron correlations in LiH, as is evident
      from a comparison with quasiparticle band structures calculated within the
      Coulomb-hole-plus-screened-exchange formalism.

PMID- 24313525
TI  - Electron correlation in oxygen vacancy in SrTiO3.
AB  - Oxygen vacancies are an important type of defect in transition metal oxides. In
      SrTiO3 they are believed to be the main donors in an otherwise intrinsic crystal.
      At the same time, a relatively deep gap state associated with the vacancy is
      widely reported. To explain this inconsistency we investigate the effect of
      electron correlation in an oxygen vacancy (OV) in SrTiO3. When taking correlation
      into account, we find that the OV-induced localized level can at most trap one
      electron, while the second electron occupies the conduction band. Our results
      offer a natural explanation of how the OV in SrTiO3 can produce a deep in-gap
      level (about 1 eV below the conduction band bottom) in photoemission, and at the
      same time be an electron donor. Our analysis implies that an OV in SrTiO3 should
      be fundamentally regarded as a magnetic impurity, whose deep level is always
      partially occupied due to the strong Coulomb repulsion. An OV-based Anderson
      impurity model is derived, and its implications are discussed.

PMID- 24313526
TI  - Universal method for separating spin pumping from spin rectification voltage of
      ferromagnetic resonance.
AB  - We develop a method for universally resolving the important issue of separating
      spin pumping from spin rectification signals in bilayer spintronics devices. This
      method is based on the characteristic distinction of spin pumping and spin
      rectification, as revealed in their different angular and field symmetries. It
      applies generally for analyzing charge voltages in bilayers induced by the
      ferromagnetic resonance (FMR), independent of FMR line shape. Hence, it solves
      the outstanding problem that device-specific microwave properties restrict the
      universal quantification of the spin Hall angle in bilayer devices via FMR
      experiments. Furthermore, it paves the way for directly measuring the nonlinear
      evolution of spin current generated by spin pumping. The spin Hall angle in a
      Py/Pt bilayer is thereby directly measured as 0.021+/-0.015 up to a large
      precession cone angle of about 20 degrees . 

PMID- 24313527
TI  - Optical conductivity measurement of a dimer Mott-insulator to charge-order phase
      transition in a two-dimensional quarter-filled organic salt compound.
AB  - We report a novel insulator-insulator transition arising from the internal charge
      degrees of freedom in the two-dimensional quarter-filled organic salt beta-(meso
      DMBEDT-TTF)2PF6. The optical conductivity spectra above Tc=70 K display a
      prominent feature of the dimer Mott insulator, characterized by a substantial
      growth of a dimer peak near 0.6 eV with decreasing temperature. The dimer peak
      growth is rapidly quenched as soon as a peak of the charge order appears below
      Tc, indicating a competition between the two insulating phases. Our infrared
      imaging spectroscopy has further revealed a spatially competitive electronic
      phase far below Tc, suggesting a nature of quantum phase transition driven by
      material-parameter variations.

PMID- 24313528
TI  - Shocks generate crossover behavior in lattice avalanches.
AB  - A spatial avalanche model is introduced, in which avalanches increase stability
      in the regions where they occur. Instability is driven globally by a driving
      process that contains shocks. The system is typically subcritical, but the shocks
      occasionally lift it into a near- or supercritical state from which it rapidly
      retreats due to large avalanches. These shocks leave behind a signature-a
      distinct power-law crossover in the avalanche size distribution. The model is
      inspired by landslide field data, but the principles may be applied to any system
      that experiences stabilizing failures, possesses a critical point, and is subject
      to an ongoing process of destabilization that includes occasional dramatic
      destabilizing events. 

PMID- 24313529
TI  - Flux saturation length of sediment transport.
AB  - Sediment transport along the surface drives geophysical phenomena as diverse as
      wind erosion and dune formation. The main length scale controlling the dynamics
      of sediment erosion and deposition is the saturation length Ls, which
      characterizes the flux response to a change in transport conditions. Here we
      derive, for the first time, an expression predicting Ls as a function of the
      average sediment velocity under different physical environments. Our expression
      accounts for both the characteristics of sediment entrainment and the saturation
      of particle and fluid velocities, and has only two physical parameters which can
      be estimated directly from independent experiments. We show that our expression
      is consistent with measurements of Ls in both aeolian and subaqueous transport
      regimes over at least 5 orders of magnitude in the ratio of fluid and particle
      density, including on Mars.

PMID- 24313530
TI  - Shock waves in weakly compressed granular media.
AB  - We experimentally probe nonlinear wave propagation in weakly compressed granular
      media and observe a crossover from quasilinear sound waves at low impact to shock
      waves at high impact. We show that this crossover impact grows with the confining
      pressure P0, whereas the shock wave speed is independent of P0-two hallmarks of
      granular shocks predicted recently. The shocks exhibit surprising power law
      attenuation, which we model with a logarithmic law implying that shock
      dissipation is weak and qualitatively different from other granular dissipation
      mechanisms. We show that elastic and potential energy balance in the leading part
      of the shocks.

PMID- 24313531
TI  - Spatial dependence of protein-water collective hydrogen-bond dynamics.
AB  - Using molecular dynamics simulations, we analyze collective vibrations in the
      hydration water of a small globular protein. We develop tools that allow spatial
      resolution of correlated protein and water motion, and use them to reveal
      correlated vibrations that extend up to 10 A from the protein surface at far
      infrared/THz frequencies that are sensitive to the chemical properties of the
      protein surface. Our results provide the first detailed description of long-range
      effects on protein hydration water dynamics and highlight the differences between
      single particle and collective dynamics, which are relevant in interpreting
      experimental observations.

PMID- 24313532
TI  - Discontinuous shear thickening of frictional hard-sphere suspensions.
AB  - Discontinuous shear thickening (DST) observed in many dense athermal suspensions
      has proven difficult to understand and to reproduce by numerical simulation. By
      introducing a numerical scheme including both relevant hydrodynamic interactions
      and granularlike contacts, we show that contact friction is essential for having
      DST. Above a critical volume fraction, we observe the existence of two states: a
      low viscosity, contactless (hence, frictionless) state, and a high viscosity
      frictional shear jammed state. These two states are separated by a critical shear
      stress, associated with a critical shear rate where DST occurs. The shear jammed
      state is reminiscent of the jamming phase of granular matter. Continuous shear
      thickening is seen as a lower volume fraction vestige of the jamming transition. 

PMID- 24313533
TI  - Optical nonlinearities and enhanced light transmission in soft-matter systems
      with tunable polarizabilities.
AB  - We demonstrate a new class of synthetic colloidal suspensions capable of
      exhibiting negative polarizabilities, and observe for the first time robust
      propagation and enhanced transmission of self-trapped light over long distances
      that would have been otherwise impossible in conventional suspensions with
      positive polarizabilities. Such light penetration through the strong scattering
      environment is attributed to the interplay between optical forces and self
      activated transparency effects while no thermal effect is involved. By
      judiciously mixing colloidal particles of both negative and positive
      polarizabilities, we show that the resulting nonlinear response of these systems
      can be fine-tuned. Our experimental observations are in agreement with
      theoretical analysis based on a thermodynamic model that takes into account
      particle-particle interactions. These results may open up new opportunities in
      developing soft-matter systems with engineered optical nonlinearities. 

PMID- 24313534
TI  - Comment on "Electron temperature scaling in laser interaction with solids".

PMID- 24313535
TI  - Kluge et al. Reply:.

PMID- 24313536
TI  - Leadership and innovation in nursing seen through a historical lens.
AB  - AIM: To explore nurses' archived accounts of Matron Muriel Powell's management
      and leadership style and the impact of this on the implementation and
      sustainability of innovation in the workplace. BACKGROUND: In popular discourse,
      the matron has become an emblem of leadership. Although the title disappeared in
      the UK in the late 1960s as part of the re-organization recommended by the Salmon
      Report, it re-appeared in 2002 in an attempt to improve care standards by
      reasserting a strong nursing presence and clinical leadership role. DESIGN:
      Secondary data analysis using qualitative thematic analysis. METHODS: This paper
      draws on interview data held in the 'Nurses Voices' archive. The interview
      transcripts of 132 nurses who trained or worked at St George's hospital in 1920
      1980 were analysed in depth between March 2011-January 2012 and themes were
      generated inductively by grouping together emergent codes in the data with
      similar meaning. RESULTS: Looking back, the nurses recalled strong memories of
      the leadership of Matron Powell. Her presence emerged as a significant influence
      throughout the interviews. Two resonant themes were identified: innovation and
      open communication. CONCLUSIONS: Through her visibility and direct access with
      patients and staff, Dame Muriel Powell showed what we would now call
      transformative leadership qualities. Her leadership created a culture of open
      communication and innovation that initiated change in the organization and the
      nursing workforce. Looking back and learning from historical figures can deepen
      understanding and provide pointers for the nurse leaders of today.

PMID- 24313537
TI  - Supramolecular functionalization and concomitant enhancement in properties of
      Au(25) clusters.
AB  - We present a versatile approach for tuning the surface functionality of an
      atomically precise 25 atom gold cluster using specific host-guest interactions
      between beta-cyclodextrin (CD) and the ligand anchored on the cluster. The
      supramolecular interaction between the Au25 cluster protected by 4-(t
      butyl)benzyl mercaptan, labeled Au25SBB18, and CD yielding Au25SBB18?CDn (n = 1,
      2, 3, and 4) has been probed experimentally using various spectroscopic
      techniques and was further analyzed by density functional theory calculations and
      molecular modeling. The viability of our method in modifying the properties of
      differently functionalized Au25 clusters is demonstrated. Besides modifying their
      optoelectronic properties, the CD moieties present on the cluster surface provide
      enhanced stability and optical responses which are crucial in view of the
      potential applications of these systems. Here, the CD molecules act as an
      umbrella which protects the fragile cluster core from the direct interaction with
      many destabilizing agents such as metal ions, ligands, and so on. Apart from the
      inherent biocompatibility of the CD-protected Au clusters, additional
      capabilities acquired by the supramolecular functionalization make such modified
      clusters preferred materials for applications, including those in biology. 

PMID- 24313538
TI  - CT-guided, minimally invasive, postmortem needle biopsy using the B-Rob II needle
      positioning robot.
AB  - CT-guided, minimally invasive needle biopsy techniques can be used to retrieve
      tissue or body fluid samples for histologic tissue diagnoses in forensic
      investigations. The purpose of this study was an evaluation of CT-guided needle
      positioning robot B-Rob II. To operate under CT guidance, we adopted the B-Rob II
      robotic needle placement system and its workflow. The accuracy and speed of the
      procedure were tested on a gelatin phantom in a series of 21 biopsies. We
      achieved an average needle placement accuracy of 1.8 mm (+/-1.1 mm) using robotic
      assistance. The procedure required an average of 2 min 21 s. The needle placement
      accuracy for minimally invasive needle biopsies using the B-Rob II biopsy robot
      is sufficiently accurate and fast for forensic postmortem examinations of focal
      organ changes. Further tests will be performed to test the feasibility of the
      robot for performing biopsies of focal organ changes in human bodies. 

PMID- 24313539
TI  - Ictal single photon emission computed tomography in epileptic auras.
AB  - OBJECTIVES: Little is known about whether ictal single photon emission computed
      tomography (SPECT) during an isolated aura can localize the epileptogenic zone
      (EZ). This study seeks to evaluate the yield of ictal SPECT injection in isolated
      epileptic auras. METHODS: We identified 20 patients with focal epilepsy studied
      during 26 isolated auras by ictal interictal subtraction SPECT coregistered to
      magnetic resonance imaging (SISCOM). Studies were rated by two readers who
      blindly scored the images for presence or absence of an area of dominant
      hyperperfusion and the lateralization and localization of ictal hyperperfusion;
      kappa statistics were calculated. Results are correlated with the localization or
      lateralization of the EZ, time of injection, and electroencephalography (EEG)
      findings during aura. RESULTS: Fourteen (53%) of 26 injections in 13 patients
      were rated by both readers as having an area of dominant hyperperfusion with poor
      interobserver agreement (k = 0.128). Nine of 26 injections in eight patients were
      correctly lateralized to the side of the EZ (kappa = 0.46), but only one of 21
      injections in one patient was correctly localized (kappa = 0.146). No difference
      was found when comparing temporal and extratemporal cases. Studies obtained in
      auras with ictal EEG change were no more likely to be correctly localized than in
      ones without (p = 0.19). The timing of injection was not a predictor of success.
      SIGNIFICANCE: Ictal SPECT injection during an isolated aura has a low yield of
      correct localization of the EZ and cannot be relied on alone during presurgical
      evaluation. A repeat injection during a seizure with clinical signs and ictal EEG
      accompaniment is recommended.

PMID- 24313540
TI  - Synthesis and self-assembly of large-area Cu nanosheets and their application as
      an aqueous conductive ink on flexible electronics.
AB  - Large-area Cu nanosheets are synthesized by a strategy of Cu nanocrystal self
      assembly, and then aqueous conductive Cu nanosheet ink is successfully prepared
      for direct writing on the conductive circuits of flexible electronics. The Cu
      nanocrystals, as building blocks, self-assemble along the [111] direction and
      grow into large-area nanosheets approximately 30-100 MUm in diameter and a few
      hundred nanometers in thickness. The laminar stackable patterns of the Cu
      nanosheet circuits increase the contact area of the Cu nanosheets and improve the
      stability of the conductor under stress, the result being that the Cu nanosheet
      circuits display excellent conductive performance during repeated folding and
      unfolding. Moreover, heterostructures of Ag nanoparticle-coated Cu nanosheets are
      created to improve the thermal stability of the nanosheet circuits at high
      temperatures.

PMID- 24313541
TI  - Shortcomings in the application of multicolour flow cytometry in lymphocyte
      subsets enumeration.
AB  - The lymphoid system is composed of numerous phenotypically distinct subsets of
      cells, each of which has a unique role in the effectiveness of an immune
      response. To distinguish specifically between these subsets, it is mandatory to
      detect simultaneously different cell surface antigens. This became feasible by
      the development of multicolour flow cytometric technologies. With these
      techniques, researchers now have the opportunity to study individual cells in far
      greater detail than previously possible. However, proper data analysis,
      interpretation and presentation of results will require a high level of
      understanding of the intricacies of the technology and the inherent limitations
      of the acquired data. The present report is intended to contribute to the better
      understanding of how the flow cytometer operates. This report may help new and
      inexperienced users to work appropriately with the flow cytometer. 

PMID- 24313542
TI  - Computer-assisted engineering of the synthetic pathway for biodegradation of a
      toxic persistent pollutant.
AB  - Anthropogenic halogenated compounds were unknown to nature until the industrial
      revolution, and microorganisms have not had sufficient time to evolve enzymes for
      their degradation. The lack of efficient enzymes and natural pathways can be
      addressed through a combination of protein and metabolic engineering. We have
      assembled a synthetic route for conversion of the highly toxic and recalcitrant
      1,2,3-trichloropropane to glycerol in Escherichia coli, and used it for a
      systematic study of pathway bottlenecks. Optimal ratios of enzymes for the
      maximal production of glycerol, and minimal toxicity of metabolites were
      predicted using a mathematical model. The strains containing the expected optimal
      ratios of enzymes were constructed and characterized for their viability and
      degradation efficiency. Excellent agreement between predicted and experimental
      data was observed. The validated model was used to quantitatively describe the
      kinetic limitations of currently available enzyme variants and predict
      improvements required for further pathway optimization. This highlights the
      potential of forward engineering of microorganisms for the degradation of toxic
      anthropogenic compounds. 

PMID- 24313543
TI  - Impact of a customised dietary intervention on antioxidant status, dietary
      intakes and periodontal indices in patients with adult periodontitis.
AB  - BACKGROUND: Dietary modification may be important in the prevention and control
      of chronic adult periodontitis. The role of promoting an adequate consumption of
      fruits, vegetables and whole grains in chronic periodontitis has not been
      thoroughly investigated. The main aim of this dietary intervention study was to
      assess the influence of a customised dietary intervention (aiming to increase the
      consumption of fruits, vegetables and whole grains) on antioxidant status in
      adults with chronic periodontitis. METHODS: Fifty-one participants, aged 30-65
      years, were recruited from a U.K. Dental Hospital and randomly allocated to an
      intervention or control group. Both groups received normal clinical treatment but
      customised dietary advice was delivered to the intervention group by a community
      nutrition assistant. Dietary intakes, anthropometric parameters and biochemical
      indices with respect to blood and saliva and periodontal indices were evaluated
      at baseline, as well as at 3 and 6 months post-dietary intervention. RESULTS: At
      3 and 6 months post-intervention, the intervention group showed a significant (P
      < 0.05) increase in plasma total antioxidant capacity measured by Trolox
      equivalent antioxidant capacity assay compared to the control group. At 3 and 6
      months after dietary intervention, the intervention group had significantly
      higher intakes of fruits and vegetables compared to the control group. The intake
      of whole grain was significantly higher in the intervention group than in the
      control group, 6 months post-intervention. No significant differences were
      observed with respect to periodontal indices between groups. CONCLUSIONS: It is
      suggested that dietary advice may help to improve dietary habits and,
      consequently, the antioxidant status of patients with chronic periodontitis.
      However, the impact of such intervention on periodontal indices needs further
      investigation.

PMID- 24313544
TI  - Inhibitory effect of liposomal solutions of grape seed extract on the formation
      of heterocyclic aromatic amines.
AB  - The effectiveness of grape seed extract (GSE) encapsulated in liposomes to
      inhibit the formation of heterocyclic aromatic amines (HAA) during frying of beef
      patties was assessed. All liposomal systems were prepared by high pressure
      homogenization at 22 500 psi. A total of six samples (rapeseed oil (control), GSE
      at 0.1% and 0.2%, and GSE-containing liposomes with 1%, 2%, and 5% soy lecithin)
      were investigated. MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline), PhIP (2
      amino-1-methyl-6-phenylimidazo[4,5b]pyridine), Norharman, and Harman were found
      after the marinade application and frying. PhIP concentrations decreased upon
      marination with GSE (0.1%) and GSE-containing liposomes (1% and 5%) (p < 0.05).
      MeIQx contents decreased in all samples compared to the oil control (p < 0.01)
      while no effect on beta-carboline formation was observed. Results are in contrast
      to previous studies that had shown that liposomal encapsulation may enhance
      effectiveness of polyphenols to inhibit radical reactions. A mechanistic model
      was proposed to explain the observed differences. 

PMID- 24313545
TI  - Circulating progenitor cells in rheumatoid arthritis: association with
      inflammation and oxidative stress.
AB  - OBJECTIVES: To evaluate the association between inflammation, oxidative stress,
      and circulating progenitor cell (CPC) number and redox equilibrium, vascular
      lesions and accelerated atherosclerosis in rheumatoid arthritis (RA). METHOD:
      Circulating CD34+ cells were isolated from 33 RA patients and 33 controls.
      Reactive oxygen species (ROS) levels and mRNA expression of manganese superoxide
      dismutase (MnSOD), catalase (CAT), glutathione peroxidase type 1 (GPx-1)
      antioxidant enzymes, and the gp91phox-containing nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase NOX2 were measured in CD34+ cells. C
      reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR), carotid
      intima-media thickness (cIMT), and arterial stiffness (AS) were also evaluated.
      We investigated the relationships between inflammatory markers, vascular
      parameters, cell number, and antioxidant enzymes. RESULTS: CD34+ cell number was
      lower in RA patients than in controls. In CD34+ cells from RA patients, ROS
      levels, MnSOD mRNA, and NOX2 mRNA were higher, while mRNA expression of GPx-1 and
      CAT was significantly lower. The AS, pulse wave velocity (PWV), and augmentation
      index (AIx) were higher, as was cIMT. CD34+ cell number was inversely correlated
      with CRP, ROS, PWV, and AIx, and with the CAT/MnSOD and GPx-1/MnSOD ratios. CRP
      was correlated with MnSOD mRNA, PWV, and AIx but not with CAT and GPx-1 mRNA.
      CONCLUSIONS: Our data show a link between inflammation, oxidative stress, and the
      impairment of the antioxidant system of CPCs and their number, and with arterial
      stiffness in RA subjects. This could suggest a perspective on the accelerated
      development of vascular damage and atherosclerosis in RA.

PMID- 24313546
TI  - The association between changes in pressure pain sensitivity and changes in
      cardiovascular physiological factors associated with persistent stress.
AB  - OBJECTIVES: To evaluate the possible association between pressure pain
      sensitivity of the chest bone (PPS) and cardiovascular physiological factors
      related to persistent stress in connection with a three-month PPS-guided stress
      reducing experimental intervention programme. METHODS: Forty-two office workers
      with an elevated PPS (>= 60 arbitrary units) as a sign of increased level of
      persistent stress, completed a single-blinded cluster randomized controlled
      trial. The active treatment was a PPS (self-measurement)-guided stress management
      programme. Primary endpoints: Blood pressure (BP), heart rate (HR) and work of
      the heart measured as Pressure-Rate-Product (PRP); Secondary endpoints: Other
      features of the metabolic syndrome. RESULTS: PPS decreased and changes in PPS
      after the intervention period were significantly associated with HR, PRP, body
      mass index (BMI) and visceral fat index (all correlation coefficients > 0.2, p <
      0.05). Compared to the control cluster group, the active cluster group obtained a
      significant reduction in PPS, Low-density lipoprotein (LDL) cholesterol and total
      number of elevated risk factors (p < 0.05). On an individual level, significant
      and clinically relevant between-group reductions were observed in respect to BP,
      HR, PRP, total and LDL cholesterol, and total number of elevated risk factors (p
      < 0.05). CONCLUSIONS: The stress intervention method applied in this study
      induced a decrease in PPS which was associated with a clinically relevant
      decrease in resting blood pressure, heart rate, work of the heart and serum
      cholesterols.

PMID- 24313547
TI  - Urinary tract infection during pregnancy affects the level of leptin, ghrelin and
      insulin in maternal and placental blood.
AB  - AIM: We examined ghrelin, leptin and insulin in maternal blood during normal
      pregnancy and pregnancy complicated by urinary tract infection (UTI), as well as
      in cord blood at labor. METHODS: A total of 36 delivering women with history of
      UTI during the third trimester of pregnancy were enrolled in the study; 12
      healthy pregnant women served as a control. Infection markers (CRP and
      procalcitonin) were determined in maternal blood during the course of UTI and at
      labor. Ghrelin, leptin and insulin were determined during labor in venous
      maternal and in umbilical cord blood. RESULTS: We found negative correlation
      between infection markers in maternal blood during UTI, and level of tested
      hormones in cord blood, indicating potential risk of placental impairment due to
      energetic imbalance. We noted lower level of leptin in mothers with UTI and no
      change in leptin from umbilical blood comparing subjects with and without UTI.
      Low level of ghrelin was observed in maternal and cord blood when pregnancy was
      complicated by UTI. Insulin concentrations were high in mothers with UTI and low
      in their newborn's cord blood. Increased maternal insulin level could indicate
      peripheral insulin resistance caused by the infection. CONCLUSION: UTI during
      pregnancy affects the concentration of hormones responsible for regulating
      energetic homeostasis within the placenta.

PMID- 24313548
TI  - Clarification of patient selection for two studies of iron deficiency.

PMID- 24313549
TI  - Childhood abuse and vulnerability to depression: cognitive scars in otherwise
      healthy young adults.
AB  - Models of depression vulnerability posit that negative early experiences, such as
      exposure to childhood abuse (CA), increase vulnerability to depression later in
      life. Though most victims of CA do not go on to develop depression, the question
      remains as to whether these individuals retain cognitive 'scars' that may
      contribute to depression vulnerability. The present study examined the
      relationship between self-reported, retrospective CA and cognitive vulnerability
      to depression in a carefully selected sample of young adults without current or
      past psychopathology. We measured cognitive vulnerability with both a self-report
      questionnaire, the Dysfunctional Attitudes Scale (DAS), and a measure of
      information processing bias, the Scrambled Sentences Test (SST). Self-reported
      severity of CA was associated with increased cognitive vulnerability to
      depression on both the DAS and SST. Vulnerability to depression as measured by
      the SST, but not by the DAS, prospectively predicted increases in depressive
      symptoms over a 6-month period. Scores on the SST also interacted with CA to
      predict increases in depressive symptoms. These findings demonstrate the
      pernicious effects of CA even in those without current or past psychopathology. 

PMID- 24313550
TI  - H/D kinetic isotope effect as a tool to elucidate the reaction mechanism of
      methyl radicals with glycine in aqueous solutions.
AB  - The H/D kinetic isotope effect (KIE) for the reaction of methyl radicals with
      glycine in aqueous solutions at pH 10.6 equals 16 +/- 3. This result proves that
      the methyl radical abstracts a hydrogen atom from the methylene group of glycine
      and not an electron from the unpaired couple on the nitrogen atom. The rate
      constant of the reaction of methyl radicals with glycine at pH 7.0 is orders of
      magnitude smaller than that at pH 10.6. 

PMID- 24313551
TI  - Quantification of the concentration of Abeta42 propagons during the lag phase by
      an amyloid chain reaction assay.
AB  - The aggregation of the amyloid beta peptide, Abeta42, implicated in Alzheimer's
      disease, is characterized by a lag phase followed by a rapid growth phase.
      Conventional methods to study this reaction are not sensitive to events taking
      place early in the lag phase promoting the assumption that only monomeric or
      oligomeric species are present at early stages and that the lag time is defined
      by the primary nucleation rate only. Here we exploit the high sensitivity of
      chemical chain reactions to the reagent composition to develop an assay which
      improves by 2 orders of magnitude the detection limit of conventional bulk
      techniques and allows the concentration of fibrillar Abeta42 propagons to be
      detected and quantified even during the lag time. The method relies on the chain
      reaction multiplication of a small number of initial fibrils by secondary
      nucleation on the fibril surface in the presence of monomeric peptides, allowing
      the quantification of the number of initial propagons by comparing the
      multiplication reaction kinetics with controlled seeding data. The quantitative
      results of the chain reaction assay are confirmed by qualitative transmission
      electron microscopy analysis. The results demonstrate the nonlinearity of the
      aggregation process which involves both primary and secondary nucleation events
      even at the early stages of the reaction during the lag-phase. 

PMID- 24313552
TI  - Menstruation during a lifespan: A qualitative study of women's experiences.
AB  - Menstruation is a natural phenomenon for women during their reproductive years.
      Our aim was to describe women's experiences of menstruation across the lifespan.
      Qualitative interviews with a narrative approach were conducted with 12 women
      between 18 and 48 years of age in Sweden. Using thematic analysis, we found
      menstruation to be a complex phenomenon that binds women together. It is
      perceived as an intimate and private matter, which makes women want to conceal
      the occurrence of menstrual bleeding. Over time, menstruation becomes a natural
      part of women's lives and gender identity. Health professionals play a central
      role supporting women to deal with menstruation.

PMID- 24313553
TI  - Thermodynamic approaches to the challenges of solubility in drug discovery and
      development.
AB  - This paper considers fundamental aspects determining the processes of drug
      compound dissolution and distribution in solvents/systems modeling biological
      media. Special attention is paid to the complex analysis of thermodynamic
      functions of sublimation and solvation/hydration processes during structural
      modification of lead/hit compounds and their influence on dissolution processes.
      The paper shows that at the first stages of drug design it is necessary to
      develop algorithms of optimizing the properties determining absorption,
      distribution, metabolism, and excretion (ADME) characteristics of molecules: in
      particular, diffusion flux density through lipophilic membranes. Using
      sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) as an example, we
      have demonstrated the efficiency of approaches to manipulating thermodynamic
      functions of the basic processes that result from delivering compounds to the
      points of their operation. We have formulated several criteria of compound
      selection for further tests. 

PMID- 24313554
TI  - Potential novel targets for Alzheimer pharmacotherapy: II. Update on secretase
      inhibitors and related approaches.
AB  - WHAT IS KNOWN AND OBJECTIVE: The prevailing theory regarding Alzheimer disease
      (AD) is that insoluble amyloid beta-peptide (Abeta) plays a critical role in the
      cortical plaques characteristic of the disease. Because Abeta is formed from the
      sequential splicing of amyloid precursor protein (APP) catalysed by 'secretase'
      enzymes (alpha, beta and gamma), clinical trials of secretase inhibitors will
      either result in beneficial pharmacotherapy or, if negative, cast doubt on the
      role of Abeta in AD. With recent clinical trial failures, is the Abeta theory
      wrong? METHODS: Literature searches were conducted on the topics of secretases
      and clinical trials, including PubMed searches, United States clinical trials
      directory, pharmaceutical company websites and news reports. The information was
      collected and evaluated for relevance and quality. RESULTS AND DISCUSSION:
      Several direct-acting (e.g. CTS-21166, LY2811376) and indirect-acting (e.g. ACI
      91) beta-secretase inhibitors and several gamma-secretase inhibitors (e.g.
      avagacestat, JNJ-40418677 and semagacestat) have not fared well in early clinical
      trials due to the lack of efficacy or concerns over possible serious side
      effects. WHAT IS NEW AND CONCLUSION: The failures of secretase inhibitors in
      clinical trials appear to bring into question the long-hypothesized association
      between AD and Abeta production. However, the disease might have been too
      advanced in these patients to benefit from this type of therapy (mainly
      preventive). Secretase inhibitors are still being studied, along with new
      diagnostic tools, with the hope of testing patients earlier, that is, with less
      advanced disease. If these trials also fail, the prevailing view of the role of
      Abeta in AD will truly be in doubt.

PMID- 24313555
TI  - Defining moments. Finding father.

PMID- 24313556
TI  - Safety of paediatric percutaneous native kidney biopsy and factors predicting
      bleeding complications.
AB  - AIM: Data on safety of paediatric percutaneous native kidney biopsy (PNKB) using
      automated biopsy devices and real-time ultrasonography are lacking. The objective
      of this study was to evaluate the safety and to identify factors predicting
      bleeding complications associated with this PNKB protocol. METHODS: A total of
      227 patients aged <18 years who underwent the first PNKB were analyzed. The
      primary outcome was bleeding complications divided into minor and major bleeding
      complications. Minor bleeding complications included perirenal haematoma and
      macroscopic haematuria. Major bleeding complications included requirement of
      blood transfusion, a higher level of care or vasopressors to maintain
      haemodynamic stability, requirement of angiographic or surgical intervention, or
      death. RESULTS: Perirenal haematoma occurred in 58 patients (25%) and macroscopic
      haematuria occurred in 46 patients (20%). Two factors were independently
      associated with perirenal haematoma in a multivariate model. These were male
      gender and weight for height Z-score <-0.5. Three patients (1.3%), all with
      perirenal haematoma had major bleeding complications (two required blood
      transfusion and one underwent surgery to repair an injured renal artery).
      CONCLUSIONS: The favourable safety information from our study is useful when
      counselling the parents and patients undergoing similar protocols. PNKB can be
      safely performed when precautions are taken to prevent bleeding. Selection of
      biopsy instruments should be tailored according to patient size.

PMID- 24313557
TI  - Thriving in long-term care facilities: instrument development, correspondence
      between proxy and residents' self-ratings and internal consistency in the
      Norwegian version.
AB  - AIMS: To develop an instrument for measuring thriving among residents in long
      term care facilities, to assess the correspondence between proxy ratings and self
      report and the internal consistency of the Norwegian version. BACKGROUND: The
      instrument was developed from the life-world concept of thriving and thereby has
      a different theoretical basis than existing 'dementia related' quality-of-life
      instruments. Thriving relates the experience of older persons to the place where
      they live. Proxy instruments need to be developed for residents in long-term care
      facilities who are not able to report their subjective experiences. DESIGN:
      Instrument development using cross-sectional survey design. METHODS: The
      instrument was developed in three versions (resident, family and staff) from a
      theory on thriving. Forty-eight triads consisting of a resident, family member
      and primary nurse from 12 Norwegian nursing homes participated. Data collection
      took place between March-December 2011. Inter-rater agreement between the groups
      was assessed by Cohen's kappa coefficient (weighted). Internal consistency was
      evaluated by Cronbach's alpha. Homogeneity was explored through item-total
      correlations. RESULTS: Agreement between residents, family members and staff was
      poor or fair (<0.41) in six of 38 items. These items were excluded. The 32-items
      instrument had satisfactory Cronbach's alpha values in each of the three samples
      and satisfactory homogeneity as item-total correlations was substantial without
      being excessive and thus indicated that items were measuring the same construct.
      CONCLUSION: The instrument appears to have internal consistency and enable
      reliable proxy measures of the thriving construct. Further psychometric
      assessment including checking for possible item redundancy is needed.

PMID- 24313558
TI  - UV emissions from low energy artificial light sources.
AB  - Energy efficient light sources have been introduced across Europe and many other
      countries world wide. The most common of these is the Compact Fluorescent Lamp
      (CFL), which has been shown to emit ultraviolet (UV) radiation. Light Emitting
      Diodes (LEDs) are an alternative technology that has minimal UV emissions. This
      brief review summarises the different energy efficient light sources available on
      the market and compares the UV levels and the subsequent effects on the skin of
      normal individuals and those who suffer from photodermatoses.

PMID- 24313560
TI  - Stable, efficient, and all-solution-processed quantum dot light-emitting diodes
      with double-sided metal oxide nanoparticle charge transport layers.
AB  - An efficient and stable quantum dot light-emitting diode (QLED) with double-sided
      metal oxide (MO) nanoparticle (NP) charge transport layers is fabricated by
      utilizing the solution-processed tungsten oxide (WO3) and zinc oxide (ZnO) NPs as
      the hole and electron transport layers, respectively. Except for the electrodes,
      all other layers are deposited by a simple spin-coating method. The resulting MO
      NP-based QLEDs show excellent device performance, with a peak luminance of 21300
      cd/m(2) at the emission wavelength of 516 nm, a maximal current efficiency of 4.4
      cd/A, and a low turn-on voltage of 3 V. More importantly, with the efficient
      design of the device architecture, these devices exhibit a significant
      improvement in device stability and the operational lifetime of 95 h measured at
      room temperature can be almost 20-fold longer than that of the standard device. 

PMID- 24313559
TI  - Synthesis of Bioconjugated sym-pentasubstituted corannulenes: experimental and
      theoretical investigations of supramolecular architectures.
AB  - Applications of supramolecular architectures span a broad range of fields from
      medicinal chemistry to materials science and gas storage, making the design and
      synthesis of such structures a goal of high interest. The unique structural and
      symmetric properties of corannulene and the recent synthetic developments of C5
      symmetric pentafunctionalized derivatives motivate efforts to synthesize
      bioconjugated-corannulene systems and investigate their supramolecular assembly
      properties. Herein is presented the synthesis of sym-pentasubstituted
      corannulenes functionalized with sugar (galactose and ribose), oligopeptide,
      nucleosides (thymidine and deoxyadenosine), and palindromic oligonucleotide
      strands. Experimental and theoretical results demonstrate capability of
      supramolecular assembly formation in these constructs. Ab initio theoretical
      modeling enables further evaluation of structure and energetics of
      oligonucleotide-functionalized corannulene formation. Results indicate formation
      of aggregates, although icosahedral supramolecular formation is not observed.
      Analyses suggest future improvements to synthetic routes to achieve icosahedral
      architectures. 

PMID- 24313561
TI  - Role of fetal autopsy as a complementary tool to prenatal ultrasound.
AB  - AIM: To correlate and compare prenatal ultrasound with fetal autopsy examination
      to detect structural births defects and provide specific diagnoses. METHODS: 141
      second trimester fetuses (<20 weeks and <500 g) where pregnancy was terminated
      for structural birth defects and/or severe intra-uterine growth restriction
      (IUGR) or intra-uterine death, referred to our tertiary care private, teaching
      hospital were examined by a team of experienced pathologist and clinical
      geneticist. Findings of pathology examination were compared to those provided by
      ultrasound examination. RESULTS: A total of 301 structural abnormalities were
      noted. Specific etiology was identified or syndromic diagnosis was possible in
      57/141 (40.4%) cases. The maximum number of systemic anomalies (45/301, 14.95%)
      was noted in the central nervous system (CNS). CNS anomalies were most commonly
      associated with facial dysmorphism including cleft lip/palate etc. There was a
      complete agreement between ultrasound and autopsy findings in 41/141 (29.07%)
      cases, additional information that did not influence the final diagnosis and/or
      counseling was obtained by autopsy in 65/1416 (46.09%) cases, while additional
      information that influenced the final diagnosis and/or counseling was provided by
      autopsy in 35/141 (24.82%) cases. CONCLUSION: Fetal autopsy serves as a
      complementary tool to fetal ultrasound due to its ability to pick up minor
      anomalies and/or anomalies that were missed on ultrasound. It may be routinely
      performed as an attempt to reach a specific diagnosis and offer appropriate
      counseling to couples, following pregnancy termination for fetal anomalies.

PMID- 24313563
TI  - Thickness-dependent crossover from charge- to strain-mediated magnetoelectric
      coupling in ferromagnetic/piezoelectric oxide heterostructures.
AB  - Magnetoelectric oxide heterostructures are proposed active layers for spintronic
      memory and logic devices, where information is conveyed through spin transport in
      the solid state. Incomplete theories of the coupling between local strain,
      charge, and magnetic order have limited their deployment into new information and
      communication technologies. In this study, we report direct, local measurements
      of strain- and charge-mediated magnetization changes in the
      La0.7Sr0.3MnO3/PbZr0.2Ti0.8O3 system using spatially resolved characterization
      techniques in both real and reciprocal space. Polarized neutron reflectometry
      reveals a graded magnetization that results from both local structural
      distortions and interfacial screening of bound surface charge from the adjacent
      ferroelectric. Density functional theory calculations support the experimental
      observation that strain locally suppresses the magnetization through a change in
      the Mn-eg orbital polarization. We suggest that this local coupling and
      magnetization suppression may be tuned by controlling the manganite and
      ferroelectric layer thicknesses, with direct implications for device
      applications. 

PMID- 24313562
TI  - Knowledge of HIV testing and attitudes towards blood donation at three blood
      centres in Brazil.
AB  - BACKGROUND: Reducing risk of HIV window period transmission requires
      understanding of donor knowledge and attitudes related to HIV and risk factors.
      STUDY DESIGN AND METHODS: We conducted a survey of 7635 presenting blood donors
      at three Brazilian blood centres from 15 October through 20 November 2009.
      Participants completed a questionnaire on HIV knowledge and attitudes about blood
      donation. Six questions about blood testing and HIV were evaluated using maximum
      likelihood chi-square and logistic regression. Test seeking was classified in non
      overlapping categories according to answers to one direct and two indirect
      questions. RESULTS: Overall, respondents were male (64%) repeat donors (67%)
      between 18 and 49 years old (91%). Nearly 60% believed blood centres use better
      HIV tests than other places; however, 42% were unaware of the HIV window period.
      Approximately 50% believed it was appropriate to donate to be tested for HIV, but
      67% said it was not acceptable to donate with risk factors even if blood is
      tested. Logistic regression found that less education, Hemope-Recife blood
      centre, replacement, potential and self-disclosed test-seeking were associated
      with less HIV knowledge. CONCLUSION: HIV knowledge related to blood safety
      remains low among Brazilian blood donors. A subset finds it appropriate to be
      tested at blood centres and may be unaware of the HIV window period. These
      donations may impose a significant risk to the safety of the blood supply.
      Decreasing test-seeking and changing beliefs about the appropriateness of
      individuals with behavioural risk factors donating blood could reduce the risk of
      transfusing an infectious unit.

PMID- 24313564
TI  - Acute poisoning types and prevalence in Shanghai, China, from January 2010 to
      August 2011.
AB  - In recent years, the number of cases of acute poisoning has increased in China,
      yet; currently, there is no detailed report published that addresses acute
      poisoning in the mainland of China. We collected biological samples from 466
      cases of suspected acute poisoning at the hospitals in Shanghai, China, and
      examined them using spectroscopy, chromatography and chromatography/mass
      spectrometry. Of the 466 cases, 230 cases (100 men and 130 women) were positively
      confirmed as acute poisonings. There were 80 types of compounds identified in
      this study. Medications were the most frequent substances identified, and the
      other substances included pesticides, multiple compounds, volatile compounds,
      natural toxins, and others. The results of this study indicate a need for
      strengthening the education about and management of the rational and safe use of
      drugs in Shanghai. 

PMID- 24313565
TI  - Impaired emotional state, quality of life and cognitive functions in young
      hypogonadal men.
AB  - The study aimed to analyse emotional state, quality of life and cognitive
      functions in young hypogonadal men. Thirty-four males with hypogonadism (age 29.1
      +/- 10.5 years) and 34 age-matched healthy males (age 30.5 +/- 11.0 years) were
      recruited. Their emotional state was evaluated by Profile of Mood States, quality
      of life - by WHO Brief Quality of Life Questionnaire - and cognitive functioning 
      by Trail Making Test and Digit Span Test of Wechsler Adult Intelligence Scale.
      It was found that young men with hypogonadism had higher depression-dejection
      (13.1 +/- 8.8 versus 7.4 +/- 5.9, P = 0.003), fatigue-inertia (10.0 +/- 5.8
      versus 7.0 +/- 4.9, P = 0.030), confusion-bewilderment (5.1 +/- 4.6 versus 2.3 +/
      3.1, P = 0.004) and lower vigour-activity (14.3 +/- 5.1 versus 17.7 +/- 4.3, P =
      0.008) levels than age- and sex-matched controls. Quality of life psychological
      (13.1 +/- 2.8 versus 15.1 +/- 1.9, P = 0.005) and social (13.6 +/- 2.4 versus
      15.7 +/- 2.0, P < 0.001) domains were significantly worse in men with
      hypogonadism than in controls. Cognitive functions were significantly worse (P <
      0.001) in men with hypogonadism than in controls, showing worse executive
      function, attention, visual scanning abilities and psychomotor speed. A
      significant correlation was found between testosterone concentration and quality
      of life psychological domain. Cognitive functioning scores were significantly
      related with FT4 concentration. It is concluded that young hypogonadal patients
      have impaired emotional state and quality of life, but the most severe impairment
      was found in cognitive functioning. 

PMID- 24313566
TI  - Coronary heart disease mortality in relation to dietary, lifestyle and
      biochemical risk factors in the countries of the Seven Countries Study: a
      secondary dataset analysis.
AB  - BACKGROUND: The present study explored coronary heart disease (CHD) mortality
      rates in 2011 in countries that participated in the Seven Countries Study (SCS)
      in relation to several dietary and anthropometric/biochemical risk factors.
      Special focus was given to Crete and the Ionian Islands. METHODS: This was a
      cross-sectional study of secondary analysis of databases using data from the
      World Health Organization, the Food and Agriculture Organization database and the
      Greek National Cadaster and Cartography Organization. Geographically weighted
      regression was applied to identify the high-risk regions in relation to the
      significant factors. RESULTS: Crete, the Ionian Islands and Japan had the lowest
      mortality rates (28.9, 30.1 and 31.2 deaths/100,000 people, respectively) in
      contrast to Serbia/Montenegro that presented the highest rates (105.1
      deaths/100,000 people). Diet, physical inactivity and hypertension were found to
      be the most significant factors in the model (P < 0.05). Regions of no risk were
      Crete, Ionian Islands and Japan (exponent B = 0.65; 95% confidence interval =
      0.293-0.942; P < 0.001), whereas Serbia/Montenegro and Finland were identified as
      high-risk areas with a 2.97-fold higher probability for CHD mortality (95%
      confidence interval = 1.736-4.028; P < 0.001). CONCLUSIONS: Observed patterns of
      CHD mortality and related factors may be helpful for appropriate management by
      health planners when aiming to reduce its prevalence, particularly in high-risk
      areas.

PMID- 24313568
TI  - Exploratory structural equation modeling: an integration of the best features of
      exploratory and confirmatory factor analysis.
AB  - Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), path
      analysis, and structural equation modeling (SEM) have long histories in clinical
      research. Although CFA has largely superseded EFA, CFAs of multidimensional
      constructs typically fail to meet standards of good measurement: goodness of fit,
      measurement invariance, lack of differential item functioning, and well
      differentiated factors in support of discriminant validity. Part of the problem
      is undue reliance on overly restrictive CFAs in which each item loads on only one
      factor. Exploratory SEM (ESEM), an overarching integration of the best aspects of
      CFA/SEM and traditional EFA, provides confirmatory tests of a priori factor
      structures, relations between latent factors and multigroup/multioccasion tests
      of full (mean structure) measurement invariance. It incorporates all combinations
      of CFA factors, ESEM factors, covariates, grouping/multiple-indicator multiple
      cause (MIMIC) variables, latent growth, and complex structures that typically
      have required CFA/SEM. ESEM has broad applicability to clinical studies that are
      not appropriately addressed either by traditional EFA or CFA/SEM. 

PMID- 24313567
TI  - Impulsive and compulsive behaviors in Parkinson's disease.
AB  - Impulsive-compulsive behaviors (ICBs) in Parkinson's disease (PD) are a common
      and devastating side effect of dopamine replacement therapy. In this review we
      describe the phenomenology, prevalence, and risk factors of patients with PD.
      Results of behavioral studies assessing the neuropsychological profile of
      patients with PD emphasize that the ICBs, which are behavioral addictions, are
      not hedonically motivated. Rather, other factors such as the inability to cope
      with uncertainty may be triggering ICBs. New insights from functional imaging
      studies, strengthening the incentive salience hypothesis, are discussed, and
      therapeutic guidelines for the management of ICBs in PD are given. 

PMID- 24313570
TI  - Excess early mortality in schizophrenia.
AB  - Schizophrenia is often referred to as one of the most severe mental disorders,
      primarily because of the very high mortality rates of those with the disorder.
      This article reviews the literature on excess early mortality in persons with
      schizophrenia and suggests reasons for the high mortality as well as possible
      ways to reduce it. Persons with schizophrenia have an exceptionally short life
      expectancy. High mortality is found in all age groups, resulting in a life
      expectancy of approximately 20 years below that of the general population.
      Evidence suggests that persons with schizophrenia may not have seen the same
      improvement in life expectancy as the general population during the past decades.
      Thus, the mortality gap not only persists but may actually have increased. The
      most urgent research agenda concerns primary candidates for modifiable risk
      factors contributing to this excess mortality, i.e., side effects of treatment
      and lifestyle factors, as well as sufficient prevention and treatment of physical
      comorbidity. 

PMID- 24313480
TI  - Searches for new physics using the tt- invariant mass distribution in pp
      collisions at ?s=8 TeV.
AB  - Searches for anomalous top quark-antiquark production are presented, based on pp
      collisions at ?s=8 TeV. The data, corresponding to an integrated luminosity of
      19.7 fb(-1), were collected with the CMS detector at the LHC. The observed tt-
      invariant mass spectrum is found to be compatible with the standard model
      prediction. Limits on the production cross section times branching fraction
      probe, for the first time, a region of parameter space for certain models of new
      physics not yet constrained by precision measurements.

PMID- 24313571
TI  - The internship imbalance in professional psychology: current status and future
      prospects.
AB  - The internship is an essential part of doctoral training in professional
      psychology. Most students access internships through the annual match sponsored
      by the Association of Psychology Postdoctoral and Internship Centers (APPIC). For
      two decades the match has seen an increasing shortfall of internship positions
      relative to applicants, exceeding 650 unmatched clinical students as of 2013.
      Efforts to solve this problem have not met appreciable success. This review
      discusses the structure of the internship placement process, including and beyond
      the APPIC match, and identifies the reasons for the failed efforts, which lie
      principally in the varied standards for an acceptable internship among doctoral
      programs. Efforts to establish a common standard and the need for a governance
      structure to enforce whatever standard is agreed upon are discussed. Projections
      for the future of the placement process and the imbalance are sketched, and links
      to other issues in the field are briefly reviewed. 

PMID- 24313569
TI  - Antidepressant use in pregnant and postpartum women.
AB  - Women in their reproductive years are at risk of experiencing depressive and
      anxiety disorders. As such, it is likely that pregnant women will undergo
      treatment with antidepressants. We review the risk of adverse birth outcomes and
      neonatal complications subsequent to antidepressant use in pregnancy. An
      inconsistent literature shows that antidepressant exposure is associated with
      shortened gestations and diminished fetal growth; these effects are small.
      Transitory neonatal signs are seen in some neonates after exposure to
      antidepressants in utero. No specific pattern of malformations has been
      consistently associated with antidepressants, with the possible exception of
      paroxetine and cardiac malformations. There is inconclusive evidence of a link
      between antidepressants in late pregnancy and persistent pulmonary hypertension
      in the newborn. Extensive study finds that antidepressants cannot be considered
      major teratogens. It is likely that confounding factors contribute to a number of
      the adverse effects found to be associated with antidepressant use in pregnancy. 

PMID- 24313572
TI  - Effect of cyclolinopeptides on the oxidative stability of flaxseed oil.
AB  - Polar compounds present in flaxseed oil increase its oxidative stability.
      Flaxseed oil becomes less stable to oxidation when filtered with silica. This
      observation may be linked to antioxidant compounds present in flaxseed oil.
      Flaxseed oil was passed over a silica adsorbent column to remove polar compounds.
      The polar compounds were then eluted from the silica absorbant using a series of
      increasingly polar solvents. The polar fractions from flaxseed oil were then
      added back to silica-treated flaxseed oil to determine the impact of fractions
      containing polar compounds on oxidative stability (induction time) at 100 
      degrees C. A polar fraction containing mainly cyclolinopeptide A (CLA, 1), but
      also containing beta/gamma- and delta-tocopherol increased the induction time of
      silica-treated flaxseed oil from 2.36 +/- 0.28 to 3.20 +/- 0.41 h. When oxidative
      stability was determined immediately after addition of the polar fractions other
      flaxseed fractions and solvent controls did not affect oil stability. However,
      when the oxidative stability index (OSI) test was delayed for three days and oil
      samples were held at room temperature after the addition of the polar fractions
      to the flaxseed oil, it was observed that the control oil treated with silica had
      become highly sensitive to oxidation. A polar fraction containing a mixture of
      CLs (1, 5, 7, 9, 11), improved the oxidative stability of peptide-free oil with
      respect to the control when the OSI measurement was made three days after adding
      the fraction. In addition, effects of 1 on the oxidative stability of peptide
      free oil containing divalent metal cations was investigated. 

PMID- 24313573
TI  - Temsirolimus for advanced renal cell carcinoma.
AB  - Renal cell carcinomas (RCCs) represent one of the ten leading cancer entities
      with an increasing incidence especially in the western world. Unfortunately,
      about 25% of the patients develop metastatic RCC (mRCC) associated with a most
      unfavorable prognosis. In the recent years, various new agents targeting VEGF or
      VEGF receptor (VEGFR) or the mTOR pathway have been approved for the treatment of
      mRCC with significant prolongation of progression-free survival and, in part, of
      overall survival (OS). Targeting the mTOR kinase is an interesting option for
      mRCC. Temsirolimus, one of the available mTOR inhibitors, has been approved as a
      single agent in poor-risk mRCC patients based on the pivotal Phase III trial
      showing a significant superiority in OS versus IFN-alpha or temsirolimus + IFN
      alpha, which has been verified by a pivotal Phase III trial. The benefit has been
      shown for clear cell carcinoma and papillary RCC as well. For poor prognosis
      patients, temsirolimus improves median survival by 3.6 months. In second-line
      treatment compared with sorafenib following first-line treatment with sunitinib
      temsirolimus showed a relative progression-free survival benefit for patients
      with nonclear cell RCC with temsirolimus. The median OS for the temsirolimus
      group was 12.27 and 16.64 months for the sorafenib group. In 2007, the US FDA
      granted approval for temsirolimus for the treatment of advanced RCC. 

PMID- 24313574
TI  - Child dental anxiety, parental rearing style and dental history reported by
      parents.
AB  - AIM: To examine the relationship between self-reported parental rearing style,
      parent's assessment of their child's dental anxiety and the dental history of
      children. MATERIALS AND METHODS: Parents of primary school children were asked to
      complete questionnaires about their parenting style, using four different
      questionnaires. Parents also completed the Child Fear Survey Schedule Dental
      Subscale (CFSS-DS) on behalf of their child and a questionnaire about the dental
      history of their child. RESULTS: 454 interview forms were available for analysis.
      Minor associations were found between dental anxiety and parenting style. Anxious
      parents were more permissive and less restrictive in their parenting style.
      Parents of children who did not visit their dentist for regular check-ups
      reported more laxness and less restrictiveness. Children who had a cavity at the
      time of investigation, children who had suffered from toothache in the past and
      children who did not have a nice and friendly dentist reported more dental
      anxiety. CONCLUSION: No clear associations between parenting style and dental
      anxiety were found. Known causes of dental anxiety were confirmed.

PMID- 24313576
TI  - Fear and/or anxiety of children and parents associated with the dental
      environment.
AB  - AIM: To assess levels of anxiety in children concerning different dental
      instruments and equipment and to relate them with parents' anxiety levels moments
      before the appointment. MATERIALS AND METHODS: Fifty children from 4 to 12 years
      of age (average of 10+/-3.07) and their respective parents were evaluated. A
      facial scale was used to assess children's anxiety levels, while the Dental
      Anxiety Scale (DAS) was used to assess parents. Friedman test was applied to
      check any differences in children's anxiety levels relative to the
      equipment/instruments, and this was complemented by the use of the Wilcoxon test
      for two-by-two comparison. In order to assess correlation between parents' and
      their children's anxiety levels, the study used Spearman correlation coefficient.
      RESULTS: With regard to parents' anxiety levels, 4% resulted as null, 18% were
      low, 56% were moderate, and 22% were exacerbated; children's anxiety level
      results were: 52% light, 44% intermediate, and 4% intense. Anxiety levels related
      to instruments/equipment were, in descending order: carpule syringe > paediatric
      forceps > dental explorer > x-ray machine > rubber dam punch > high speed
      handpiece > rubber dam forceps > mouth mirror > clinical tweezers > dental chair.
      No correlation was found between parents' anxiety levels and those of their
      children (p=0.546). CONCLUSION: The instruments/equipment used in the assessment
      generated different anxiety levels in the children. No correlation was found
      between parents' anxiety levels and those of their children.

PMID- 24313577
TI  - Efficacy trial of Camouflage Syringe to reduce dental fear and anxiety.
AB  - AIM: Dental fear and anxiety in early childhood are widely prevalent and
      contribute to dental problems and behaviour in adulthood. Novel ways to reduce
      dental fear and anxiety in children are needed. Our aim was to conduct an
      efficacy trial of a novel Camouflage Syringe to reduce dental fear and anxiety in
      children. MATERIALS AND METHODS:  STUDY DESIGN: randomised controlled trial of
      efficacy of the Camouflage Syringe. We designed a Camouflage Syringe with a toy
      like appearance that veils the conventional syringe to permit topical application
      and injection of local anaesthesia and ensure more involvement of the patient in
      the treatment process. We conducted a concurrent parallel, randomised controlled
      trial (NCT01398007) on the efficacy of this Camouflage Syringe to reduce the
      dental fear and anxiety in children seeking dental treatment who required the use
      of local anaesthesia. RESULTS: Using Venham's clinical rating scale, Venham's
      picture test, parental stress questionnaire and recall questionnaire, the
      efficacy of the Camouflage Syringe to reduce dental fear and anxiety ranged from
      82% to 97% for various outcomes and from 60% to 100% for prevention of related
      adverse outcomes. For all outcomes, the number needed to treat was close to
      unity. CONCLUSION: Our results strongly favour the use of Camouflage Syringe to
      reduce dental fear and anxiety in children.

PMID- 24313575
TI  - Factors affecting psychological stress in children who cooperate with dental
      treatment: a pilot study.
AB  - AIM: Few studies have examined psychological stress and personal anxiety in
      children exhibiting cooperative behaviour during dental treatment. We assessed
      psychological stress and personal anxiety during dental treatment in cooperative
      children, and investigated the influence of various factors. MATERIALS AND
      METHODS: We measured pre- and post-treatment salivary alpha amylase (sAA) levels
      of 28 children aged 8-13 years and their parents. Children completed the State
      Trait Anxiety Inventory for Children (STAIC); their parents completed the STAI.
      The IA group included children whose sAA levels increased >10%, whereas the DA
      group included children whose sAA levels decreased >10%. We used regression
      models to calculate the power of variables to predict children's psychological
      stress. RESULTS: The mean anxiety trait score in the IA group was significantly
      higher than in the DA group (t-test, P = 0.021). For children with higher STAIC
      Trait scores, the OR for increasing sAA was 1.16 (95% CI [1.02-1.31]). Parental
      or treatment factors did not significantly contribute to incremental sAA levels
      in children. CONCLUSION: Well-behaved children with high anxiety traits may
      experience high stress levels during dental treatment; however, parental and
      dental treatment factors may not affect psychological stress in these children.

PMID- 24313578
TI  - Salivary biomarkers, vital signs and behaviour of pre-school children during
      their first dental visit.
AB  - AIM: Anxiety may influence dental treatment unfavourably, thus evaluation of the
      psychophysiological reactions of the child may reduce its negative effects. This
      study aimed to evaluate and correlate the levels of cortisol and alpha-amylase,
      vital signs and behaviour of children during their first dental visit. METHODS:
      Study sample consisted of 32 children (11 male and 21 female patients) aged
      between 4 and 6 years, who would go to the dentist for the first time, with no
      pain or chronic illness, and without the use of medication. Three saliva samples
      were collected: before, immediately after and 20 minutes after the dental
      procedure (dental prophylaxis). STATISTICS: Data were analysed using Student's t
      test and Pearson's correlation test (p = 0.05). RESULTS: In the comparison of the
      levels of alpha-amylase, the heart rate and blood pressure were higher after the
      dental visit and the levels of salivary cortisol were significantly higher
      before. There was no statistically significant difference in the correlation
      between the Frankl Behaviour Rating Scale and the levels of cortisol and alpha
      amylase, but the results showed that the levels of these two salivary biomarkers
      increased gradually as the child had a less cooperative behaviour. CONCLUSION The
      sample revealed that the first dental visit generated anxiety, which was
      manifested through physiological and behavioural alterations.

PMID- 24313579
TI  - Anxiety and pain during dental treatment among children with haemophilia.
AB  - AIM: Dental interventions are potentially overwhelming for children with
      hemophilia; the study was designed to assess the levels of dental anxiety related
      to the first dental intervention for these children. MATERIALS AND METHODS: Fifty
      six boys with severe haemophilia A and B and 56 healthy peers between the ages of
      7-12 in need of primary dental extraction were chosen for this study. Facial
      Analog Scale and Visual Analog Scale were applied to all participants. RESULTS:
      No significant differences among the groups were detected by means of the dental
      anxiety scores (FIS) and pain scores (VAS). The FIS scores of children who had
      experienced dental pain before the treatment were significantly higher regardless
      of the group they were part of (p=0.001). CONCLUSION: Children with haemophilia
      are not at an increased risk of dental anxiety using special precautions and with
      the help of adequate treatment regimens. Pain is a predictor for dental fear and
      anxiety on dental chair both for children with haemophilia and healthy ones.

PMID- 24313580
TI  - Post-operative pain and anxiety related to dental procedures in children.
AB  - AIM: To determine post-operative pain in children following treatment in the
      dental chair and its relation to dental anxiety. METHODS: A group of 125
      children, aged 5 to 18 years, attending for dental treatment had their pain
      recorded post-operatively using the revised version of the Faces Pain Scale (FPS
      R) and the Visual Analogue Scale (VAS). Baseline anxiety scores were also
      recorded using the Modified Child Dental Anxiety Scale (faces) (MCDASf). RESULTS:
      The mean MCDASf score was 20.1. Post-operative pain was reported in 62% of
      children at 2 hours, 51% at 4, and 47% at 6 hours. The surgical subgroup reported
      the most pain (79%), whereas the conservative treatment for primary teeth group
      reported the least pain (37%). Anxious patients (MCDASf > = 17) were more likely
      to report pain than less anxious patients at 2 (p=0.02) and 6 (p=0.03) hours post
      operatively. CONCLUSION: Dental procedures are associated with post-operative
      pain in children. Anxious patients are more likely to report pain.

PMID- 24313581
TI  - Temporomandibular joint dysfunction in Moebius syndrome.
AB  - AIM: Moebius syndrome is a rare condition characterised by bilateral facial and
      abducens nerve paralysis. In the present study, it was investigated the effect of
      the long term facial muscles hypoactivity on temporomandibular joint movements
      development. METHODS: Accordingly with Terzis classification (Terzis, 2003), a
      wide sample of A type and B type Moebius patients was investigated for mandibular
      range of movements. Moebius patients were compared with a sample of healthy
      subjects. RESULTS: Both type A and type B Moebius patients develop a severe
      articular movement reduction, especially during mouth opening. A highly
      significant difference was found between Moebius patients and the healthy group.
      No difference was found between A and B Moebius sub-samples. CONCLUSION: The
      authors stress the importance of an early adequate rehabilitation of Moebius
      patients, in order to avoid the limitation of TMJ movement range.

PMID- 24313582
TI  - Oral habits as risk factors for anterior open bite in the deciduous and mixed
      dentition - cross-sectional study.
AB  - AIM: Anterior open bite (AOB) is an occlusal anomaly commonly associated with
      oral habits (OH). The aim of this study was to determine the prevalence of OH as
      a risk factor for the AOB. MATERIALS AND METHODS: A group of children aged
      between 3 and 12 years were observed. The statistical methodology included
      independent chi-square test, Fisher's exact test and binary logistic regression.
      RESULTS: The frequency of oral habits was of 43.5% in the deciduous dentition and
      54.2% in the mixed dentition. There was a statistically significant association
      of pacifier sucking: 61.7 and 16.1 odd ratios (OR), and tongue thrust: 3.9 and
      9.2 OR with AOB in both groups, respectively. Thumb sucking occurred only in the
      deciduous dentition with 5.6 OR. CONCLUSION: OH and AOB have a high frequency in
      children. They hinder the normal development of dental and skeletal structures.
      As OH are risk factors for AOB, the damaging habits most frequently associated
      are: pacifier sucking, thumb sucking, and tongue thrust. Due to the correlation
      between the prevalence of AOB and OH, prevention strategies incorporating
      psychological data related to children should be integrated into a national
      public health programme.

PMID- 24313583
TI  - Effects of maltitol and xylitol chewing-gums on parameters involved in dental
      caries development.
AB  - AIM: The effects on plaque parameters of sugar free chewing-gums (CG) sweetened
      with either maltitol or xylitol were assessed to better understand the role
      polyols can play in dental caries prevention. MATERIALS AND METHODS: A double
      blind, parallel, randomised, controlled study was conducted in China. Subjects (N
      = 258, age = 13 to 15 years-old) were divided into 4 groups: 2 receiving polyols
      CG, containing respectively maltitol or xylitol, a group receiving gum base
      (placebo) and a negative control group not receiving any gum. CG were chewed for
      30 days. This corresponds to a 10 g consumption of polyol per day. Plaque
      parameters (growth, pH, bacteria and insoluble glucans) were evaluated throughout
      the experimental period. RESULTS: All parameters studied were significantly
      modified with gum base compared to no-gum: plaque pH increased; plaque growth,
      bacteria (S. mutans, S. sobrinus, A. viscosus and Lactobacillus) and insoluble
      glucans decreased. Maltitol and xylitol CG led similarly to a higher plaque pH
      (AUC, p?0.05) on short (at baseline after the first CG consumption) and long term
      (after 4 weeks of daily CG consumption), with or without saliva stimulation
      compared to both control and placebo groups. They led to a decrease in plaque
      growth (p=0.02) over the experimental period compared to controls. Moreover, they
      significantly reduced the concentration of 4 cariogenic bacteria species (p?0.05)
      in dental plaque compared to gum base. CONCLUSION: Sugar free CG sweetened with
      either maltitol or xylitol can similarly reduce plaque acidogenicity compared to
      gum base through a decrease in oral bacteria presence. The use of a gum base
      placebo allowed to isolate effects on parameters involved in dental caries
      development specific to maltitol and xylitol, and to show these effects were
      similar.

PMID- 24313584
TI  - Oral habits in a population of Albanian growing subjects.
AB  - AIM: The aim of this study was to assess the prevalence of oral habits in an
      Albanian population of schoolchildren. MATERIALS AND METHODS:  STUDY DESIGN: A
      sample of 2617 subjects, aged 7-15, was examined by clinical observation without
      radiograms. The sample comprised 1257 males and 1360 females, with no history of
      orthodontic treatment. Aestethical frontal and profile analysis, intraoral and
      functional analysis were performed. STATISTICS: Gender and age differences were
      compared by chi-square test. The relationship between malocclusions and oral
      habits was assessed by t-test and the level of significance was assessed at 0.01.
      RESULTS: The findings indicated that oral habits were present in 2225 subjects
      (85.0%), 1103 males (87.7%) and 1121 females (82.4%); the most frequent oral
      habit was pacifier sucking (30%) and it was mostly present in the 7-11 years
      group. It was observed a significant correlation between oral habits and dental
      malocclusions, open bite, altered overjet and maxillary contraction. CONCLUSION
      The high number of oral habits observed in the studied sample suggest that
      prevention strategies adopted in other countries could be successfully integrated
      in the development of an effective national programme in Albania aimed at
      reducing malocclusion risk factors.

PMID- 24313585
TI  - Prevalence of malocclusion in Italian schoolchildren and orthodontic treatment
      need.
AB  - AIM: The aim of the study was to estimate the prevalence of malocclusion and the
      need for orthodontic treatment in a sample of 3,017 Italian schoolchildren.
      MATERIALS AND METHODS:  STUDY DESIGN: 1,375 males and 1,642 females, aged between
      8 and 13 years, were visited in primary and secondary schools. Signs of
      malocclusion were registered according to an occlusal index by trained and
      calibrated operators. First the prevalence of malocclusion was calculated in
      accordance to a scale of need for orthodontic treatment (R.O.M.A. index), which
      considers both malocclusion signs and risk factors for worsening of malocclusion
      without any treatment and during craniofacial development. Then the distribution
      of the most frequent characteristics, signs and symptoms was evaluated both
      within each risk grade and in the basic sample. RESULTS: The overall percentage
      of children classified as 3, 4 and 5 grade accounted for 75.8% of the sample. The
      percentage of children classified as 4 and 5 grade are similar to those found in
      other European countries. The most frequent features found are poor oral hygiene,
      caries and early loss of deciduous teeth, deviation from full intercuspation,
      increased overbite and overjet. CONCLUSION: This epidemiological research
      describes the current orthodontic treatment need in Italy in children with a late
      mixed dentition.

PMID- 24313586
TI  - In vitro comparison of the bond strength to the enamel of conventional and self
      etching dental fissure sealants.
AB  - AIM: Dental caries in pits and fissures of molars is still very common in young
      people, despite a gradual reduction in their incidence and prevalence. Prevention
      with the aid of dental fissure sealants can help to reduce the onset of decay. In
      vitro tests were conducted to compare the bond strength to enamel of self-etching
      sealants versus those applied using the conventional procedure. METHODS: The
      lingual surface of 40 extracted, caries-free, mandibular third molars was milled
      to make them flat. The prepared teeth were randomly divided into two groups of 20
      teeth each: those in Group A were treated with Clinpro (3M ESPE, St. Paul, MN,
      USA); those in Group B with Quick Seal (BJM Laboratories Ltd, Or-Yehuda, Israel).
      Cylinders of sealant were attached to the enamel of the flat surfaces of the
      samples using a polymerisation process treating the surfaces involved according
      to the type of material. All samples underwent load testing by means of a
      universal test machine. RESULTS: The results of the load testing, measured in
      MPa, were analysed using the Student's t-test for independent samples and the
      differences proved significant, indicating that the traditionally- applied
      sealant (mean strength 21.06 MPa) assured a significantly stronger bond (p <.05)
      than the self-etching sealant (mean strength 10.43 MPa) under our experimental
      conditions. CONCLUSION Conventional sealants generally provide a considerably
      higher bond strength than self-etching sealants.

PMID- 24313587
TI  - Oral health status in liver transplant Italian children.
AB  - AIM: The aim of this study was to assess the oral health status in children
      submitted to liver transplantation in order to evaluate the need to promote
      suitable dental caries prevention programmes. MATERIALS AND METHODS: Thirty-eight
      children submitted to liver transplantation (4-5 years) were selected and their
      data were compared to those of an age-matched control healthy group of 78
      children. Clinical examinations were carried out and X-ray bitewings were taken,
      in order to record caries prevalence, caries experience, periodontal health and
      dental enamel defects. A questionnaire investigating demographic and oral health
      behaviour data was completed by parents. RESULTS: Caries prevalence was 78.9% in
      the liver transplantation group and 39.7% in the healthy control group. The dmft
      mean value was 2.26+/-2.25 in the liver transplantation group and 0.69+/-1.51 in
      the healthy group. The difference in the mean dmft between the two groups was
      statistically significant (p<0.0001). From the elaboration of the data on
      periodontal health it resulted that 23.7% of the liver transplantation subjects
      and 48.7% of controls had a healthy periodontal status, respectively; 39.5% of
      the liver transplantation children and 23.6% of the controls had plaque and
      calculus. In addition, 44.7% of the liver transplantation patients and 28.2%% of
      the control subjects showed bleeding on probing. In the liver transplantation
      subjects there was a higher prevalence (65.8%) of dental enamel defects with
      respect to the healthy group (21.8%). CONCLUSION: The high prevalence of caries
      and gingival diseases showed the need to promote specific dental caries
      prevention programmes in liver transplant children.

PMID- 24313588
TI  - Tooth developmental anomalies in severe combined immunodeficiency disease and
      juvenile myelomonocytic leukemia: common clinical features and treatment
      outcomes.
AB  - AIM: Human Severe Combined Immunodeficiency (SCID) is a prenatal disorder of T
      lymphocyte development that depends on the expression of numerous genes. Juvenile
      myelomonocytic leukemia (JMML), previously known as juvenile chronic myeloid
      leukemia (JCML), is a rare, myelodysplastic/myeloproliferative disease typically
      presenting in early childhood. CASE REPORTS: Two cases are described of
      immunodeficiency disorders, both treated with chemotherapeutic drugs (Busulfan
      plus cyclophosphamide) before bone marrow transplantation. After treatment, these
      two different cases showed several similar oral lesions: microdontia, root
      alterations, numerous tooth ageneses, incomplete calcification, enamel
      hypoplasia, premature apexification and hypodontia. Both subjects underwent
      dental and orthodontic treatment. The first phase comprised orthopaedic treatment
      using a removable appliance (Interim-G(r)) followed by rapid palatal expansion;
      in the second phase patients underwent tooth extraction and were treated using
      fixed appliances for 19 and 26 months, respectively (mean 2 years) to obtain
      final alignment and maximum intercuspation. In the third and final phase,
      reconstruction of malformed teeth was completed, and implant-supported protheses
      were applied. CONCLUSION: The difficulties of managing and treating these
      diseases are discussed, with particular focus on tooth anomalies and malocclusion
      disorders. Collaboration between dentist and paediatrician in dealing with
      patients with a variety of oral lesions and tooth anomalies is important in order
      to prevent any other possible tooth lesions and ensure correct jaw development.

PMID- 24313589
TI  - Rare case of desmoid-type fibromatosis of the mandibular region in a child:
      diagnosis and surgical management.
AB  - AIM: Desmoid-type fibromatosis is a broad group of rare disorders that originate
      from musculoaponeurotic structures. They represent less than 0,1% off all tumors
      and the annual incidence is 2-4 cases per million, with two peaks between 6 and
      15 years of age and between puberty and age 40. They are rare in the oral and
      maxillofacial regions. Its pathogenesis is multifactorial. The treatment is still
      mainly represented, both in children and adults, by surgical excision. CASE
      REPORT: A case is reported of a 8-year- old girl with desmoid fibroma in the
      mandible who presented at the Department of Pediatric Dentistry with a swelling
      measuring 4x4 cm on the lower edge of the right mandible which had appeared a few
      months earlier and slowly developed. The family dentist had initially diagnosed
      it as an odontogenic abscess from the lower right deciduous molars, but the
      antibiotic therapy was unsuccessful. After x-ray examination, which showed a
      large osteolytic lesion, mandibular CT revealed a solid expanding mass. The child
      was referred to the Department of Paediatric Maxillofacial Surgery where the
      whole mass was surgically removed. At the 2-year follow-up no relapse was noted.
      CONCLUSION: This case stresses the importance, especially for paediatric
      dentists, of further diagnostic steps if suspect lesions do not heal after
      conventional treatment.

PMID- 24313590
TI  - Lack of expression of an alternative CD20 transcript variant in circulating B
      cells from patients with pemphigus.
AB  - We have identified a spliced mRNA transcript of CD20 (named D393-CD20) which was
      associated with resistance to RTX in primary B cell from patients with lymphoma
      and leukaemia. In the present work, we wished to investigate whether D393-CD20
      variant was expressed by B cells from patients with pemphigus. Ten patients with
      bullous pemphigoid and twenty-five patients with pemphigus were included. All
      patients were responder to conventional immunosuppressive agents or rituximab (n
      = 11). Efficacy of B-cell activation by pokeweed mitogen was assessed by CD86
      expression using a FACS Canto II flow cytometer. mRNA CD20 expression study was
      then performed using RT-PCR assay allowing first to discriminate wild-type (wt)
      CD20 and D393-CD20 transcript. Although wt-CD20 expression was always detected,
      we were unable to detect D393-CD20, even after B-cell activation or RTX
      treatment. Our results suggest that D393-CD20 transcript may be a molecular
      marker of B-cell malignancies rather than autoimmune disease like pemphigus.
      Further study of RTX non-responders or non-escaping PV patients is thus still
      required to appreciate whether D393-CD20 expression may be detected under the
      pressure of RTX therapy.

PMID- 24313591
TI  - Polyoxometalate-catalyzed insertion of oxygen from O(2) into tin-alkyl bonds.
AB  - The polyoxometalate H5PV2Mo10O40 mediates the insertion of an oxygen atom from
      H5PV2Mo10O40 into the tin-carbon bond of n-Bu4Sn through its activation by
      electron transfer to yield 1-butanol and (n-Bu3Sn)2O. The reaction is initiated
      by electron transfer from n-Bu4Sn to H5PV(V)2Mo10O40 to yield the ion pair n
      Bu4Sn(*+)-H5PV(IV)V(V)Mo10O40. The H5PV(IV)V(V)Mo10O40 moiety was identified by
      UV-vis and EPR. DFT calculations show that n-Bu4Sn(*+)-H5PV(IV)V(V)Mo10O40 is
      relatively unstable and forms more stable Bu(+) and Bu3Sn(+) cations coordinated
      to the polyoxometalate, which were also identified by ESI-MS. Products are
      released at higher temperatures. In the presence of molecular oxygen as the
      terminal oxidant the reaction is catalytic. 

PMID- 24313592
TI  - The representation of compound headedness in the mental lexicon: a picture naming
      study in aphasia.
AB  - Most compound words are constituted of a head constituent (e.g., light in
      moonlight) and a modifier constituent (e.g., moon in moonlight); the information
      transmitted by these head-modifier roles is fundamental for defining the
      grammatical and semantic properties of the compound and for identifying a correct
      combination of the constituents at the conceptual level. The objective of this
      study is to assess how lexical processing in aphasia is influenced by the head
      modifier structure of nominal compounds. A picture-naming task of 35 compounds
      with head-initial (pescespada, swordfish, literally fishsword) and head-final
      (autostrada, highway, literally carroad) forms was administered to 45 Italian
      aphasic patients, and their accuracy in retrieving constituents was analysed with
      a mixed-effects logistic regression. The interaction between headedness and
      constituent position was significant: The modifier emerged as being more
      difficult to retrieve than the head, but only for head-final compounds. The
      results are consistent with previous data from priming experiments on healthy
      subjects and provide convincing evidence that compound headedness is represented
      at central processing levels. 

PMID- 24313593
TI  - Letter to the editor concerning the viewpoint; "recognizing the limitations of
      Performance Reference Compound (PRC)-calibration technique in passive water
      sampling".

PMID- 24313594
TI  - Differentiating suicide attempters from suicide ideators: a critical frontier for
      suicidology research.
AB  - Most individuals who consider suicide do not make suicide attempts. It is
      therefore critical to identify which suicide ideators are at greatest risk of
      acting on their thoughts. However, few seminal theories of suicide address which
      ideators go on to make attempts. In addition, perhaps surprisingly, most oft
      cited risk factors for suicide-such as psychiatric disorders, depression,
      hopelessness, and even impulsivity-distinguish poorly between those who attempt
      suicide and those who only consider suicide. This special section of Suicide and
      Life-Threatening Behavior serves to highlight this knowledge gap and provide new
      data on differences (and similarities) between suicide attempters and suicide
      ideators. 

PMID- 24313595
TI  - The role of glucosinolates and the jasmonic acid pathway in resistance of
      Arabidopsis thaliana against molluscan herbivores.
AB  - Although slugs and snails play important roles in terrestrial ecosystems and
      cause considerable damage on a variety of crop plants, knowledge about the
      mechanisms of plant immunity to molluscs is limited. We found slugs to be natural
      herbivores of Arabidopsis thaliana and therefore investigated possible resistance
      mechanisms of this species against several molluscan herbivores. Treating wounded
      leaves with the mucus residue ('slime trail') of the Spanish slug Arion
      lusitanicus increased wound-induced jasmonate levels, suggesting the presence of
      defence elicitors in the mucus. Plants deficient in jasmonate biosynthesis and
      signalling suffered more damage by molluscan herbivores in the laboratory and in
      the field, demonstrating that JA-mediated defences protect A. thaliana against
      slugs and snails. Furthermore, experiments using A. thaliana mutants with altered
      levels of specific glucosinolate classes revealed the importance of aliphatic
      glucosinolates in defending leaves and reproductive structures against molluscs.
      The presence in mollusc faeces of known and novel metabolites arising from
      glutathione conjugation with glucosinolate hydrolysis products suggests that
      molluscan herbivores actively detoxify glucosinolates. Higher levels of aliphatic
      glucosinolates were found in plants during the night compared to the day, which
      correlated well with the nocturnal activity rhythms of slugs and snails. Our data
      highlight the function of well-known antiherbivore defence pathways in resistance
      against slugs and snails and suggest an important role for the diurnal regulation
      of defence metabolites against nocturnal molluscan herbivores. 

PMID- 24313596
TI  - Sunscreens--what is the ideal testing model?
AB  - Sunscreen protection assessment methodologies have been evolving in tandem with
      the innovation and evolution of sunscreen products themselves; from initial human
      testing in the Swiss Alps, to laboratory testing with high intensity solar
      simulators, to spectrophotometers with modern CCD array photocells and diffuse
      reflectance spectroscopy techniques. The progress in the science leads regulatory
      development of standard methods, and provides new and improved ways to assess
      sunscreen protection properties. This review scans much of the history of the
      development of these methods and highlights the latest development in non
      invasive sunscreen testing as an opportunity to improve accuracy while
      eliminating human UV exposures.

PMID- 24313598
TI  - Relation between remission status and attention in patients with schizophrenia.
AB  - AIM: Patients with schizophrenia in remission have shown significantly higher
      levels of neurocognitive function than patients not in remission. However,
      previous studies have mainly examined the association between neurocognitive
      function and the remission status of schizophrenia without considering the time
      component of the definition for remission using cross-sectional methods. The
      purpose of this study was to investigate the relations between remission status
      with considering time components and three cognitive functions of intellectual
      ability, memory and attention, which were examined before fulfilling the
      remission criteria, using longitudinal methods. METHODS: We assessed the
      remission status using the Positive and Negative Syndrome Scale (PANSS) on the
      same patients twice: at recruitment and at 6 months after the first PANSS
      assessment. Cognitive tests were performed within 3 months after recruitment. At
      recruitment, 337 patients were enrolled. Of the patients, 63 patients were
      followed up and completedthe first and second PANSS assessments and three
      cognitive tests at the end of study. RESULTS: Of the patients, 33 patients
      fulfilled the remission criteria, while 30 patients did not fulfill the criteria.
      Patients in remission showed significantly higher levels of 2-digit (P = 0.020)
      and 3-digit (P = 0.015) Continuous Performance Test scores,
      attention/concentration in the Wechsler Memory Scale-Revised (P = 0.034) and
      processing speeds in the Wechsler Adult Intelligence Scale-III (P = 0.047) than
      patients not in remission. Additionally, these cognitive scores were positively
      correlated with each other (P < 0.05). CONCLUSION: Our findings suggest that
      patients who achieve remission may demonstrate a pre-existing higher level of
      attention than patients who do not achieve remission.

PMID- 24313597
TI  - Functional connectivity of hippocampal networks in temporal lobe epilepsy.
AB  - OBJECTIVE: Temporal lobe epilepsy (TLE) affects brain areas beyond the temporal
      lobes due to connections of the hippocampi and other temporal lobe structures.
      Using functional connectivity magnetic resonance imaging (MRI), we determined the
      changes of hippocampal networks in TLE to assess for a more complete distribution
      of abnormality. METHODS: Regions of interest (ROIs) were defined in the right and
      left hippocampi in three groups of participants: left TLE (n = 13), right TLE (n
      = 11), and healthy controls (n = 16). Brain regions functionally connected to
      these ROIs were identified by correlating resting-state low-frequency functional
      MRI (fMRI) blood oxygenation level-dependent (BOLD) signal fluctuations. The
      grouped results were compared using independent sample t-test. RESULTS: TLE was
      associated with increased hippocampal connectivity involving several key areas of
      the limbic network (temporal lobe, insula, thalamus), frontal lobes, angular
      gyrus, basal ganglia, brainstem, and cerebellum, along with reduced connectivity
      involving areas of the sensorimotor cortex (visual, somatosensory, auditory,
      primary motor) and the default mode network (precuneus). Left TLE had more marked
      connectivity changes than right TLE. SIGNIFICANCE: The observed connectivity
      changes in TLE indicate dysfunctional networks that underlie widespread brain
      involvement in TLE. There are identifiable differences in the connectivity of the
      hippocampi between left and right TLE.

PMID- 24313599
TI  - Sexuality in advanced age in Jewish thought and law.
AB  - Judaism has a positive attitude to sexual relations within a marriage, and views
      such sexual relations as important not only for procreation but also as part of
      the framework of marriage. This is true for any age group, and sexuality is seen
      as an essential element of marriage for couples of advanced age. In this article,
      the authors present the views of Jewish law and thought regarding sexuality among
      older couples. The authors illustrate this using 3 case studies of couples who
      sought guidance in the area of sexuality. In addition, this area of counseling
      benefits greatly from an ongoing relationship and dialogue between expert rabbis
      in the field and therapists treating older Orthodox Jewish patients for sexual
      dysfunction. The triad relationship of couple, therapist, and rabbi enhances the
      ability to treat and assist such couples to seek treatment and overcome their
      difficulties. 

PMID- 24313600
TI  - Baking soda misuse as a home remedy: case experience of the California Poison
      Control System.
AB  - WHAT IS KNOWN AND OBJECTIVE: Baking soda is a common household product promoted
      by the manufacturer as an antacid. It contains sodium bicarbonate and has the
      potential for significant toxicity when ingested in excessive amounts.
      Characterizing the patterns and outcomes from the misuse of baking soda as a home
      remedy can guide the clinical assessment and preventative counselling of patients
      at risk for use of this product. METHODS: We conducted a retrospective review of
      all symptomatic cases involving ingestion and misuse of a baking soda powder
      product that were reported to the California Poison Control System between the
      years 2000 and 2012. RESULTS AND DISCUSSION: Of the 192 cases we identified,
      55.8% were female, ages ranged 2 months to 79 years, and the most common reasons
      for misuse included antacid (60.4%), 'beat a urine drug test' (11.5%) and treat a
      UTI (4.7%). Most cases (55.2%) had significant symptoms warranting a medical
      evaluation, whereas 12 patients required hospital admission developed either
      electrolyte imbalances, metabolic alkalosis or respiratory depression. WHAT IS
      NEW AND CONCLUSION: Misuse of baking soda can result in serious electrolyte and
      acid/base imbalances. Patients at highest risk of toxicity may include those who
      chronically use an antacid, those who use the method to 'beat' urine drug
      screens, pregnant women and young children. Self-treatment with baking soda as a
      home remedy may also mask or delay medical care thereby complicating or
      exacerbating an existing medical problem. We suggest that healthcare providers
      counsel high-risk patients about the potential complications of misuse of baking
      soda as a home remedy.

PMID- 24313601
TI  - Ultrafiltration of uranyl peroxide nanoclusters for the separation of uranium
      from aqueous solution.
AB  - Uranyl peroxide cluster species were produced in aqueous solution by the
      treatment of uranyl nitrate with hydrogen peroxide, lithium hydroxide, and
      potassium chloride. Ultrafiltration of these cluster species using commercial
      sheet membranes with molecular mass cutoffs of 3, 8, and 20 kDa (based on
      polyethylene glycol) resulted in U rejection values of 95, 85, and 67% by mass,
      respectively. Ultrafiltration of untreated uranyl nitrate solutions using these
      membranes resulted in virtually no rejection of U. These results demonstrate the
      ability to use the filtration of cluster species as a means for separating U from
      solutions on the basis of size. Small-angle X-ray scattering, Raman spectroscopy,
      and electrospray ionization mass spectrometry confirmed the presence of uranyl
      peroxide cluster species in solution and were used to characterize their size,
      shape, and dispersity. 

PMID- 24313602
TI  - Vapor-phase molecular doping of graphene for high-performance transparent
      electrodes.
AB  - Doping is an essential process to engineer the conductivity and work-function of
      graphene for higher performance optoelectronic devices, which includes
      substitutional atomic doping by reactive gases, electrical/electrochemical doping
      by gate bias, and chemical doping by acids or reducing/oxidizing agents. Among
      these, the chemical doping has been widely used due to its simple process and
      high doping strength. However, it also has an instability problem in that the
      molecular dopants tend to gradually evaporate from the surface of graphene,
      leading to substantial decrease in doping effect with time. In particular, the
      instability problem is more serious for n-doped graphene because of undesirable
      reaction between dopants and oxygen or water in air. Here we report a simple
      method to tune the electrical properties of CVD graphene through n-doping by
      vaporized molecules at 70  degrees C, where the dopants in vapor phase are mildly
      adsorbed on graphene surface without direct contact with solution. To investigate
      the dependence on functional groups and molecular weights, we selected a series
      of ethylene amines as a model system, including ethylene diamine (EDA),
      diethylene triamine (DETA), and triethylene tetramine (TETA) with increasing
      number of amine groups showing different vapor pressures. We confirmed that the
      vapor-phase doping provides not only very high carrier concentration but also
      good long-term stability in air, which is particularly important for practical
      applications. 

PMID- 24313603
TI  - Virtually simulated social pressure influences early visual processing more in
      low compared to high autonomous participants.
AB  - In a previous study, we showed that virtually simulated social group pressure
      could influence early stages of perception after only 100  ms. In the present EEG
      study, we investigated the influence of social pressure on visual perception in
      participants with high (HA) and low (LA) levels of autonomy. Ten HA and ten LA
      individuals were asked to accomplish a visual discrimination task in an adapted
      paradigm of Solomon Asch. Results indicate that LA participants adapted to the
      incorrect group opinion more often than HA participants (42% vs. 30% of the
      trials, respectively). LA participants showed a larger posterior P1 component
      contralateral to targets presented in the right visual field when conforming to
      the correct compared to conforming to the incorrect group decision. In
      conclusion, our ERP data suggest that the group context can have early effects on
      our perception rather than on conscious decision processes in LA, but not HA
      participants.

PMID- 24313604
TI  - The influence of dynamic response and brain deformation metrics on the occurrence
      of subdural hematoma in different regions of the brain.
AB  - OBJECT: The purpose of this study was to examine how the dynamic response and
      brain deformation of the head and brain-representing a series of injury
      reconstructions of which subdural hematoma (SDH) was the outcome-influence the
      location of the lesion in the lobes of the brain. METHODS: Sixteen cases of falls
      in which SDH was the outcome were reconstructed using a monorail drop rig and
      Hybrid III headform. The location of the SDH in 1 of the 4 lobes of the brain
      (frontal, parietal, temporal, and occipital) was confirmed by CT/MR scan examined
      by a neurosurgeon. RESULTS: The results indicated that there were minimal
      differences between locations of the SDH for linear acceleration. The peak
      resultant rotational acceleration and x-axis component were larger for the
      parietal lobe than for other lobes. There were also some differences between the
      parietal lobe and the other lobes in the z-axis component. Maximum principal
      strain, von Mises stress, shear strain, and product of strain and strain rate all
      had differences in magnitude depending on the lobe in which SDH was present. The
      parietal lobe consistently had the largest-magnitude response, followed by the
      frontal lobe and the occipital lobe. CONCLUSIONS: The results indicated that
      there are differences in magnitude for rotational acceleration and brain
      deformation metrics that may identify the location of SDH in the brain.

PMID- 24313605
TI  - Deep brain stimulation and microelectrode recording.

PMID- 24313606
TI  - Enlargement of the sella turcica in pseudotumor cerebri.
AB  - OBJECT: The sella turcica usually appears partially empty in MR images obtained
      from patients with chronic elevation of intracranial pressure. The authors
      measured the size of the sella turcica to determine if enlargement of the
      pituitary fossa explains the partially empty sella associated with pseudotumor
      cerebri. METHODS: The medical records from 2005 to 2011 of a single neuro
      ophthalmologist were searched to identify consecutive patients with pseudotumor
      cerebri. Age-matched control patients were selected from the same practice. The
      sella turcica and pituitary gland were measured on sagittal T1-weighted MR
      images. RESULTS: Measurements were obtained for 48 patients with pseudotumor
      cerebri and 48 controls. The cross-sectional area of the sella was 38% greater in
      the patients with pseudotumor cerebri, with only a slight reduction in mean
      pituitary gland size. CONCLUSIONS: Chronic elevation of intracranial pressure is
      associated with bony enlargement of the sella turcica. Enlargement of the sella
      turcica contributes to its partially empty appearance.

PMID- 24313608
TI  - Higher risk for meningioma in women with uterine myoma: a nationwide population
      based retrospective cohort study.
AB  - OBJECT: Evidence suggests that hormones play a role in modifying both uterine
      myoma (UM) and meningioma. A number of studies have observed the positive
      association between these diseases. The aim of the current population-based study
      was to determine if women with UM are at a higher risk for meningioma. METHODS:
      The authors used data from the National Health Insurance system of Taiwan for the
      study. The UM cohort contained 281,244 women. Each woman was randomly frequency
      matched with 4 women without UM, based on age, index year of diagnosis,
      occupation, urbanization (urbanization level was categorized by the population
      density of the residential area into 4 levels, with Level 1 as the most urbanized
      and Level 4 as the least urbanized), and comorbidity, to form the control cohort.
      Cox's proportional hazard regression analysis was conducted to estimate the
      influence of UM on the meningioma risk. RESULTS: Among women with UM, the risk of
      developing meningioma was significantly higher (45%) than among women without UM
      (95% CI 1.23-1.70). The same phenomenon was observed among most age groups, but a
      significant difference was only seen in the middle-age range. For women with UM,
      further analysis did not show a significant change after myomectomy. The
      cumulative incidence of meningioma between groups with and without UM differed
      over time. CONCLUSIONS: The nationwide population-based cohort study found that
      Taiwanese women with UM are at higher risk for developing meningioma.

PMID- 24313607
TI  - Acute subdural hematoma from bridging vein rupture: a potential mechanism for
      growth.
AB  - Most acute subdural hematomas (ASDHs) develop after rupture of a bridging vein or
      veins. The anatomy of the bridging vein predisposes to its tearing within the
      border cell layer of the dura mater. Thus, the subdural hematoma actually forms
      within the dura. The hematoma grows by continued bleeding into the border cell
      layer. However, the venous pressure would not be expected to cause a large
      hematoma. Therefore, some type of mechanism must account for the hematoma's
      expansion. Cerebral venous pressure (CVP) has been demonstrated in animal models
      to be slightly higher than intracranial pressure (ICP), and CVP tracks the ICP as
      pressure variations occur. The elevation of CVP as the ICP increases is thought
      to result from an increase in outflow resistance of the terminal portion of the
      bridging veins. This probably results from a Starling resistor model or, less
      likely, from a muscular sphincter. A hypothesis is derived to explain the
      mechanism of ASDH enlargement. Tearing of one or more bridging veins causes these
      vessels to bleed into the dural border cell layer. Subsequent ICP elevation from
      the ASDH, cerebral swelling, or other cause results in elevation of the CVP by
      increased outflow resistance in the intact bridging veins. The increased ICP
      causes further bleeding into the hematoma cavity via the torn bridging veins.
      Thus, the ASDH enlarges via a positive feedback mechanism. Enlargement of an ASDH
      would cease as blood within the hematoma cavity coagulates. This would stop the
      dissection of the dural border cell layer, and pressure within the hematoma
      cavity would equalize with that in the torn bridging vein or veins.

PMID- 24313609
TI  - Risk factors indicating the need for cranial CT scans in elderly patients with
      head trauma: an Austrian trial and comparison with the Canadian CT Head Rule.
AB  - OBJECT: This study presents newly defined risk factors for detecting clinically
      important brain injury requiring neurosurgical intervention and intensive care,
      and compares it with the Canadian CT Head Rule (CCHR). METHODS: This prospective
      cohort study was conducted in a single Austrian Level-I trauma center and
      enrolled a consecutive sample of mildly head-injured adults who presented to the
      emergency department with witnessed loss of consciousness, disorientation, or
      amnesia, and a Glasgow Coma Scale (GCS) score of 13-15. The studied population
      consisted of a large number of elderly patients living in Vienna. The aim of the
      study was to investigate risk factors that help to predict the need for immediate
      cranial CT in patients with mild head trauma. RESULTS: Among the 12,786 enrolled
      patients, 1307 received a cranial CT scan. Four hundred eighty-nine patients
      (37.4%) with a mean age of 63.9 +/- 22.8 years had evidence of an acute traumatic
      intracranial lesion on CT. Three patients (< 0.1%) were admitted to the intensive
      care unit for neurological observation and received oropharyngeal intubation.
      Seventeen patients (0.1%) underwent neurosurgical intervention. In 818 patients
      (62.6%), no evidence of an acute trauma-related lesion was found on CT. Data
      analysis showed that the presence of at least 1 of the following factors can
      predict the necessity of cranial CT: amnesia, GCS score, age > 65 years, loss of
      consciousness, nausea or vomiting, hypocoagulation, dementia or a history of
      ischemic stroke, anisocoria, skull fracture, and development of a focal
      neurological deficit. Patients requiring neurosurgical intervention were detected
      with a sensitivity of 90% and a specificity of 67% by using the authors'
      analysis. In contrast, the use of the CCHR in these patients detected the need
      for neurosurgical intervention with a sensitivity of only 80% and a specificity
      of 72%. CONCLUSIONS: The use of the suggested parameters proved to be superior in
      the detection of high-risk patients who sustained a mild head trauma compared
      with the CCHR rules. Further validation of these results in a multicenter setting
      is needed. Clinical trial registration no.: NCT00451789 ( ClinicalTrials.gov .).

PMID- 24313610
TI  - The relationship between ruptured aneurysm location, subarachnoid hemorrhage clot
      thickness, and incidence of radiographic or symptomatic vasospasm in patients
      enrolled in a prospective randomized controlled trial.
AB  - OBJECT: Cerebral vasospasm following subarachnoid hemorrhage (SAH) causes
      significant morbidity in a delayed fashion. The authors recently published a new
      scale that grades the maximum thickness of SAH on axial CT and is predictive of
      vasospasm incidence. In this study, the authors further investigate whether
      different aneurysm locations result in different SAH clot burdens and whether any
      concurrent differences in ruptured aneurysm location and maximum SAH clot burden
      affect vasospasm incidence. METHODS: Two hundred fifty patients who were part of
      a prospective randomized controlled trial were reviewed. Most outcome and
      demographic variables were included as part of the prospective randomized
      controlled trial. Additional variables were also collected at a later time,
      including vasospasm data and maximum clot thickness. RESULTS: Aneurysms were
      categorized into 1 of 6 groups: intradural internal carotid artery aneurysms,
      vertebral artery (VA) aneurysms (including the posterior inferior cerebellar
      artery), basilar trunk or basilar apex aneurysms, middle cerebral artery
      aneurysms, pericallosal aneurysms, and anterior communicating artery aneurysms.
      Twenty-nine patients with nonaneurysmal SAH were excluded. Patients with
      pericallosal aneurysms had the least average maximum clot burden (5.3 mm),
      compared with 6.4 mm for the group overall, but had the highest rate of
      symptomatic vasospasm (56% vs 22% overall, OR 4.9, RR 2.7, p = 0.026).
      Symptomatic vasospasm occurrence was tallied in patients with clinical
      deterioration attributable to delayed cerebral ischemia. There were no
      significant differences in maximum clot thickness between aneurysm sites. Middle
      cerebral artery aneurysms resulted in the thickest mean maximum clot (7.1 mm) but
      rates of symptomatic and radiographic vasospasm in this group were statistically
      no different compared with the overall group. Vertebral artery aneurysms had the
      worst 1-year modified Rankin scale (mRS) scores (3.0 vs 1.9 overall,
      respectively; p = 0.0249). A 1-year mRS score of 0-2 (good outcome) was found in
      72% of patients overall, but in only 50% of those with pericallosal and VA
      aneurysms, and in 56% of those with basilar artery aneurysms (p = 0.0044).
      Patients with stroke from vasospasm had higher mean clot thickness (9.71 vs 6.15
      mm, p = 0.004). CONCLUSIONS: The location of a ruptured aneurysm minimally
      affects the maximum thickness of the SAH clot but is predictive of symptomatic
      vasospasm or clinical deterioration from delayed cerebral ischemia in
      pericallosal aneurysms. The worst 1-year mRS outcomes in this cohort of patients
      were noted in those with posterior circulation aneurysms or pericallosal artery
      aneurysms. Patients experiencing stroke had higher mean clot burden.

PMID- 24313611
TI  - Aneurysm rupture.

PMID- 24313613
TI  - The lucid interval and the role of Benjamin Bell.

PMID- 24313612
TI  - Incidence of cranial nerve palsy after preoperative embolization of glomus
      jugulare tumors using Onyx.
AB  - OBJECT: The resection of glomus jugulare tumors can be challenging because of
      their inherent vascularity. Preoperative embolization has been advocated as a
      means of reducing operative times, blood loss, and surgical complications.
      However, the incidence of cranial neuropathy associated with the embolization of
      these tumors has not been established. The authors of this study describe their
      experience with cranial neuropathy following transarterial embolization of glomus
      jugulare tumors using ethylene vinyl alcohol (Onyx, eV3 Inc.). METHODS: The
      authors retrospectively reviewed all cases of glomus jugulare tumors that had
      been treated with preoperative embolization using Onyx at their institution in
      the period from 2006 to 2012. Patient demographics, clinical presentation, grade
      and amount of Onyx used, degree of angiographic devascularization, and procedural
      complications were recorded. RESULTS: Over a 6-year period, 11 patients with
      glomus jugulare tumors underwent preoperative embolization with Onyx. All
      embolization procedures were completed in one session. The overall mean percent
      of tumor devascularization was 90.7%. No evidence of nontarget embolization was
      seen on postembolization angiograms. There were 2 cases (18%) of permanent
      cranial neuropathy attributed to the embolization procedures (facial nerve
      paralysis and lower cranial nerve dysfunction). CONCLUSION: Embolizing glomus
      jugulare tumors with Onyx can produce a dramatic reduction in tumor vascularity.
      However, the intimate anatomical relationship and overlapping blood supply
      between these tumors and cranial nerves may contribute to a high incidence of
      cranial neuropathy following Onyx embolization.

PMID- 24313614
TI  - Onyx embolization.

PMID- 24313615
TI  - Intraoperative rerupture during surgical treatment of aneurysmal subarachnoid
      hemorrhage is not associated with an increased risk of vasospasm.
AB  - OBJECT: Intraoperative rerupture during open surgical clipping of cerebral
      aneurysms in subarachnoid hemorrhage (SAH) is a relatively frequent and
      potentially catastrophic occurrence. Patients who suffer rerupture have been
      shown to have worse outcomes at discharge compared with those who do not have
      rerupture. Perioperative injury likely plays a large part in the clinical
      worsening of these patients. However, due to the increased vessel manipulation
      and repeat exposure to acute hemorrhage, it is possible that secondary injury
      from increased incidence of vasospasm also contributes. Identifying an increased
      rate of vasospasm in these patients would justify early aggressive treatment with
      measures to prevent delayed cerebral ischemia. The authors investigated whether
      patients who suffer intraoperative rerupture during surgical treatment of
      ruptured cerebral aneurysms are at increased risk of developing vasospasm.
      METHODS: Five hundred consecutive patients treated with open surgical clipping
      for SAH were reviewed, and clinical and imaging data were collected. Angiographic
      vasospasm was defined as vessel narrowing believed to be consistent with
      vasospasm on angiography. Symptomatic vasospasm was defined as angiographic
      vasospasm in the setting of a clinical change attributable to vasospasm. Rates of
      angiographic and symptomatic vasospasm among patients with and without
      intraoperative rerupture were compared. RESULTS: There were no significant
      differences between the groups with and without rupture with respect to age, sex,
      modified Fisher grade, history of hypertension, or smoking. The group with
      intraoperative rupture had more patients with Hunt and Hess Grade I. Angiographic
      vasospasm was noted in 279 (66%) of the 425 patients without rerupture compared
      with 49 (65%) of the 75 patients with rerupture (p = 1.0, Fisher's exact test).
      Symptomatic vasospasm was noted in 154 (36%) of the 425 patients without
      rerupture, compared with 31 (41%) of the 75 patients with rerupture (p = 0.44,
      Fisher's exact test). In multivariate analysis, higher modified Fisher grade was
      significantly predictive of vasospasm, whereas older age and male sex were
      protective. CONCLUSIONS: This study found no significant influence of
      intraoperative rerupture during open surgical clipping on the rate of
      angiographic or symptomatic vasospasm. Brief exposure to acute hemorrhage and
      vessel manipulation associated with rerupture events did not affect the rate of
      vasospasm. Risk of vasospasm was related to increased modified Fisher grade, and
      inversely related to age and male sex. These results do not justify early,
      targeted vasospasm therapy in patients with intraoperative rerupture.

PMID- 24313616
TI  - Impact of target location on the response of trigeminal neuralgia to stereotactic
      radiosurgery.
AB  - OBJECT: The authors evaluate the impact of target location on the rate of pain
      relief (PR) in patients with intractable trigeminal neuralgia (TN) undergoing
      stereotactic radiosurgery (SRS). METHODS: The authors conducted a retrospective
      review of 99 patients with idiopathic TN who were identified from a prospectively
      maintained database and were treated with SRS targeting the dorsal root entry
      zone with a maximum dose of 80 Gy. Targeting of the more proximal portion of a
      trigeminal nerve with the 50% isodose line overlapping the brainstem was
      performed in 36 patients (proximal group). In a matched group, 63 patients
      received SRS targeting the 20% isodose line tangential to the emergence of the
      brainstem (distal group). The median follow-up time was 33 months (range 6-124
      months). RESULTS: The actuarial rate of maintenance of Barrow Neurological
      Institute (BNI) Pain Score I-IIIa was attained in 89% of patients at 1 year, 81%
      at 2 years, and 69% at 4 years, respectively, after SRS. Kaplan-Meier analysis
      revealed that durability of PR was only associated with the proximal location of
      the radiosurgical target (log-rank test, p = 0.018). Radiosurgery-induced facial
      numbness (BNI Score II or III) developed in 35 patients, which was significantly
      more frequent in the proximal group (19 patients [53%] compared with 16 [25%] in
      the distal group [p = 0.015]). CONCLUSIONS: The radiosurgical target appears to
      affect the duration of pain relief in patients with idiopathic trigeminal
      neuralgia with the target closer to the brainstem affording extended pain relief.
      However, the proximal SRS target was also associated with an increased risk of
      mild to moderate facial numbness.

PMID- 24313617
TI  - The impact of extent of resection on malignant transformation of pure
      oligodendrogliomas.
AB  - OBJECT: Recent evidence suggests that a greater extent of resection (EOR) extends
      malignant progression-free survival among patients with low-grade gliomas (LGGs).
      These studies, however, rely on the combined analysis of oligodendrogliomas,
      astrocytomas, and mixed oligoastrocytomas-3 histological subtypes with distinct
      genetic and molecular compositions. To assess the value of EOR in a homogeneous
      LGG patient population and delineate its impact on LGG transformation, the
      authors examined its effect on newly diagnosed supratentorial oligodendrogliomas.
      METHODS: The authors identified 93 newly diagnosed adult patients with WHO Grade
      II oligodendrogliomas treated with microsurgical resection at Barrow Neurological
      Institute. Clinical, laboratory, and radiographic data were collected
      retrospectively, including 1p/19q codeletion status and volumetric analysis based
      on T2-weighted MRI. RESULTS: The median preoperative and postoperative tumor
      volumes and EOR were 29.0 cm(3) (range 1.3-222.7 cm(3)), 5.2 cm(3) (range 0-156.1
      cm(3)), and 85% (range 6%-100%), respectively. Median follow-up was 75.4 months,
      and there were 14 deaths (15%). Progression and malignant progression were
      identified in 31 (33%) and 20 (22%) cases, respectively. A greater EOR was
      associated with longer overall survival (p = 0.005) and progression-free survival
      (p = 0.004); however, a greater EOR did not prolong the interval to malignant
      progression, even when controlling for 1p/19q codeletion. CONCLUSIONS: A greater
      EOR is associated with an improved survival profile for patients with WHO Grade
      II oligodendrogliomas. However, for this particular LGG patient population, the
      interval to tumor transformation is not influenced by cytoreduction. These data
      raise the possibility that the capacity for microsurgical resection to modulate
      malignant progression is mediated through biological mechanisms specific to
      nonoligodendroglioma LGG histologies.

PMID- 24313618
TI  - A forensic and medical evaluation of dog bites in a province of Western Turkey.
AB  - The aim was to evaluate the demographic data of dog-bite cases organized from
      criminal and forensic reports. This study evaluated 328 cases admitted to the
      Director of Forensic Medicine, Eskisehir, as a result of dog bites between
      January 1, 2006 and December 31, 2010. It was found that those in the age-group
      of 0-18 were most frequently exposed to dog bites (48.5%). Injuries to the lower
      extremity, upper extremity, and chest/abdomen/back were more frequent in men
      (72.6%, 76.4%, and 66.1%, respectively), while injuries to the head/neck/face
      were more frequent in women (52.3%) (p < 0.01). While most of those wounded in
      the upper extremity, the head/neck/face, and the chest/abdomen/back were in the
      child age-group, most of those wounded in the lower extremity were in the adult
      age-group (p < 0.001). Teaching children, in particular, how to behave around
      dogs would be useful in reducing the incidence of bite. 

PMID- 24313619
TI  - Efficacy of porcine placental extract on wrinkle widths below the eye in
      climacteric women.
AB  - OBJECTIVE: Injections of human placental extract, which is known to play a role
      in skin regulation, have long been used for the treatment of skin wrinkles and
      non-healing wounds. Porcine placental extract (PPE), an oral supplement, was
      recently developed for this purpose. The aim of this study was to assess whether
      PPE has a positive effect on the improvement of fine wrinkles below the eye in
      climacteric women. METHODS: We first non-invasively measured wrinkle widths with
      a skin analyzer in a cross-section of 185 healthy adult Japanese women. Next, 44
      climacteric women with mild or few climacteric symptoms were enrolled into an
      open-label, randomized, controlled study of the effect of PPE on wrinkle widths.
      A retrospective comparison of wrinkle widths in 123 climacteric women with
      climacteric symptoms with or without PPE treatment was also performed. RESULTS:
      Wrinkle widths below the eye in women >= 30 years of age were significantly
      higher than in women 20-29 years of age. Treatment with three capsules of PPE per
      day was significantly (p < 0.05) effective in reducing wrinkle widths at 24 weeks
      compared with control subjects. Retrospective analysis showed that subjects
      treated with three (p < 0.05) and six (p < 0.01) capsules of PPE per day observed
      a significant reduction in wrinkle widths compared with untreated subjects.
      CONCLUSION: Oral PPE treatment is a possible option for improving the appearance
      of fine wrinkles below the eye in climacteric women.

PMID- 24313620
TI  - Water intakes and dietary sources of a nationally representative sample of Irish
      adults.
AB  - BACKGROUND: Despite evidence that even mild dehydration is associated with
      various morbidities, water intake estimates in free-living populations are
      lacking. The present study aimed to estimate water intakes and dietary sources in
      a nationally representative sample of the Irish adult population. METHODS: A 4
      day semi-weighed food record was used to collect dietary intake data from 1500
      free-living adults aged 18-90 years in the Irish National Adult Nutrition Survey
      (NANS) (2008-2010) from which water intake was estimated. To enable fluid intake
      estimation, additional questions on how water and milk were consumed were
      incorporated. Total water intake was calculated as drinking water plus water from
      other beverages and food moisture. RESULTS: The mean (SD) daily total water
      intake for Irish adults was 2.31 (0.92) L day(-1) [males 2.52 (1.00) L day(-1) ;
      females 2.09 (0.79) L day(-1)]. Intakes were lowest in elderly adults, as well as
      in those with less education, a lower social class, less energy expenditure and a
      higher body mass index and body fat percentage. In total, 67% of water came from
      beverages and 33% came from food moisture. Alcoholic beverages and teas
      individually contributed to total water intake in amounts similar to the drinking
      water contribution. CONCLUSIONS: These data may be used as a foundation for
      further research in the area of the effect of under consumption of water on
      health outcomes to guide public health messages regarding adequate water intakes.

PMID- 24313621
TI  - Spontaneous assembly of carbon-based chains in polymer matrixes through surface
      charge templates.
AB  - Stable chains of carbon-based nanoparticles were formed directly in polymer
      matrixes through an electrode-free approach. Spontaneous surface charges were
      generated pyroelectrically onto functionalized ferroelectric crystals, enabling
      the formation of electric field gradients that triggered the dipole-dipole
      interactions responsible for the alignment of the particles, while embedded in
      the polymer solution. The phenomenon is similar to the dielectrophoretic
      alignment of carbon nanotubes reported in the literature. However, here the
      electric fields are generated spontaneously by a simple heat treatment that,
      simultaneously, aligns the particles and provides the energy necessary for curing
      the host polymer. The result is a polymer sheet reinforced with well-aligned
      chains of carbon-based particles, avoiding the invasive implementation of
      appropriate electrodes and circuits. Because polymers with anisotropic features
      are of great interest for enhancing the thermal and/or the electrical
      conductivity, the electrode-free nature of this technique would improve the
      scaling down and the versatility of those interconnections that find applications
      in many fields, such as electronics, sensors, and biomedicine. Theoretical
      simulations of the interactions between the particles and the charge templates
      were implemented and appear in good agreement with the experimental results. The
      chain formation was characterized by controlling different parameters, including
      surface charge configuration, particle concentration, and polymer viscosity, thus
      demonstrating the reliability of the technique. Moreover, micro-Raman
      spectroscopy and scanning electron microscopy were used for a thorough inspection
      of the assembled chains. 

PMID- 24313622
TI  - Photoinduced single-molecule magnet properties in a four-coordinate iron(II) spin
      crossover complex.
AB  - The four-coordinate Fe(II) complex, PhB(MesIm)3Fe-N?PPh3 (1) has been previously
      reported to undergo a thermal spin-crossover (SCO) between high-spin (HS, S = 2)
      and low-spin (LS, S = 0) states. This complex is photoactive below 20 K,
      undergoing a photoinduced LS to HS spin state change, as determined by optical
      reflectivity and photomagnetic measurements. With continuous white light
      irradiation, 1 displays slow relaxation of the magnetization, i.e. single
      molecule magnet (SMM) properties, at temperatures below 5 K. This complex
      provides a structural template for the design of new photoinduced mononuclear
      SMMs based on the SCO phenomenon. 

PMID- 24313623
TI  - Hot flushes in women with breast cancer: state of the art and future
      perspectives.
AB  - Although not life-threatening, vasomotor symptoms might have a detrimental effect
      on quality of life and represent a major determinant of poor therapeutic
      compliance in breast cancer patients. Limitations of hormonal therapies have
      fostered the use of non-estrogenic pharmacological agents, which mainly include
      centrally acting compounds, antidepressant drugs, serotonin-norepinephrine
      reuptake inhibitors and serotonin reuptake inhibitors. Integrating therapeutic
      tools have recently come from a wide range of heterogeneous approaches varying
      from phytoestrogens use to ganglion block. We herein critically review the most
      updated evidence on the available treatment options for management of vasomotor
      symptoms. The need for a patient-oriented approach following systematic
      evaluation of the presence and degree of vasomotor disturbances is also discussed
      and future perspectives in therapeutics are summarized. 

PMID- 24313624
TI  - Oral vitamin D increases the frequencies of CD38+ human B cells and ameliorates
      IL-17-producing T cells.
AB  - Vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nm) has been associated with
      the onset of immunological diseases including atopic dermatitis (AD), cutaneous
      or systemic lupus erythematosus and allergic asthma. In this study, we assessed
      whether oral vitamin D (cholecalciferol) supplementation leads to a systemic
      modulation of the phenotype of circulating lymphocyte populations and whether a
      defined serum 25-hydroxyvitamin D (25(OH)D) concentration can be related to the
      effects on lymphocytes. Cholecalciferol was administered in a dose-escalation
      setting to vitamin D-deficient individuals from 2000 up to 8000 IU daily for 12
      weeks. Individuals without cholecalciferol intake served as controls. Peripheral
      B cells and T cells were examined by multicolour flow cytometric analysis. The
      mean serum 25(OH)D concentrations increased upon cholecalciferol intake up to 159
      +/- 28.7 nm, and remained low in the control group 30.0 +/- 12.5 nm. Following
      cholecalciferol intake, the frequencies of circulating CD38 expressing B cells
      were significantly increased and IFN-gamma+ , and/or IL-17+ CD4+ T helper cells
      were decreased. These data were identified to correlate with the serum 25(OH)D
      levels by applying two different analysis approaches (ROC and a nonlinear
      regression analysis). Our data indicate that increasing 25(OH)D serum
      concentrations are associated with an increased expression of CD38 on B cells and
      a decreased T-cell-dependent proinflammatory cytokine production. The
      therapeutical role of our findings in systemic immunological diseases should be
      explored in the future by further controlled clinical studies.

PMID- 24313625
TI  - "Jumping to conclusions" in delusion-prone participants: an experimental
      economics approach.
AB  - INTRODUCTION: That delusional and delusion-prone individuals "jump to
      conclusions" on probabilistic reasoning tasks is a key finding in cognitive
      neuropsychiatry. Here we focused on a less frequently investigated aspect of
      "jumping to conclusions" (JTC): certainty judgments. We incorporated rigorous
      procedures from experimental economics to eliminate potential confounds of
      miscomprehension and motivation and systematically investigated the effect of
      incentives on task performance. METHODS: Low- and high-delusion-prone
      participants (n = 109) completed a series of computerised trials; on each trial,
      they were shown a black or a white fish, caught from one of the two lakes
      containing fish of both colours in complementary ratios. In the betting
      condition, participants were given L4 to distribute over the two lakes as they
      wished; in the control condition, participants simply provided an estimate of how
      probable each lake was. Deviations from Bayesian probabilities were investigated.
      RESULTS: Whereas high-delusion-prone participants in both the control and betting
      conditions underestimated the Bayesian probabilities (i.e. were conservative),
      low-delusion-prone participants in the control condition underestimated but those
      in the betting condition provided accurate estimates. In the control condition,
      there was a trend for high-delusion-prone participants to give higher estimates
      than low-delusion-prone participants, which is consistent with previous reports
      of "jumping to conclusions" in delusion-prone participants. However, our findings
      in the betting condition, where high-delusion-prone participants provided lower
      estimates than low-delusion-prone participants (who were accurate), are
      inconsistent with the jumping-to-conclusions effect in both a relative and an
      absolute sense. CONCLUSIONS: Our findings highlight the key role of task
      incentives and underscore the importance of comparing the responses of delusion
      prone participants to an objective rational standard as well as to the responses
      of non-delusion-prone participants.

PMID- 24313626
TI  - A mixed effects model to estimate timing and intensity of pubertal growth from
      height and secondary sexual characteristics.
AB  - AIM: To estimate and compare pubertal growth timing and intensity in height,
      Tanner stage markers and testis volume. SUBJECTS AND METHODS: Data on height,
      genital stage, breast stage and pubic hair stage, testis volume and menarche in
      103 boys and 74 girls from the Edinburgh Longitudinal Growth Study were analysed.
      The SITAR model for height and a novel mixed effects logistic model for Tanner
      stage and testis volume provided estimates of peak velocity (PV, intensity) and
      age at peak velocity (APV, timing), both overall (from fixed effects) and for
      individuals (random effects). RESULTS: Based on the six markers, mean APV was
      13.0-14.0 years in boys and 12.0-13.1 years in girls, with between-subject
      standard deviations of ~1 year. PV for height was 8-9 cm/year by sex and for
      testis volume 6 ml/year, while Tanner stage increased by 1.2-1.8 stages per year
      at its peak. The correlations across markers for APV were 0.6-0.8 for boys and
      0.8-0.92 for girls, very significantly higher for girls (p = 0.005). Correlations
      for PV were lower, -0.2-0.6. CONCLUSIONS: The mixed effects models perform well
      in estimating timing and intensity in individuals across several puberty markers.
      Age at peak velocity correlates highly across markers, but peak velocity less so.

PMID- 24313627
TI  - The effect of shame-proneness, guilt-proneness, and internalizing tendencies on
      nonsuicidal self-injury.
AB  - Nonsuicidal self-injury is especially common in adolescents and young adults.
      Self-injury may be related to shame or guilt--two moral emotions--as these
      differentially predict other maladaptive behaviors. Using a college sample, we
      examined not only how shame-proneness, guilt-proneness, and internalizing
      emotional tendencies related to self-injury, but also whether these moral
      emotions moderate the relation between internalizing tendencies and self-injury.
      High shame-proneness was associated with higher frequencies of self-injury. High
      guilt-proneness was associated with less self-injury, although this effect was
      mitigated at higher levels of internalizing tendencies. These results suggest
      shame-proneness is a risk factor for self-injury, while guilt-proneness is
      protective.

PMID- 24313628
TI  - p53 and mitogen-activated protein kinase pathway protein profiles in fresh and
      frozen spermatozoa.
AB  - Sperm or testicular tissue cryopreservation is performed in cases of male
      infertility as a treatment for the preservation of fertility. When these sperm
      cells are used in assisted reproductive techniques, fertilisation rates,
      developmental and implantation potential of embryos decrease and the abortion
      rates increase. In the present work, differences of both phosphorylation and
      expression levels of p53 and Mitogen-activated protein kinases (MAPK) proteins
      were analysed in 61 individual sperm samples before and after cryopreservation.
      We observed that p53 protein residue at Ser 15 was phosphorylated after
      cryopreservation. Because MAPK pathway activations may be involved in p53
      phosphorylation, MAPK/ERK, Stress-activated protein kinases (SAPK)/JNK and
      p38MAPK proteins were also investigated. Analysis showed that p38MAPK
      phosphorylations increased significantly. However, ERK and JNK expressions and
      phosphorylations decreased, although the differences were not statistically
      significant. According to our results, it may be suggested that cryopreservation
      process activates p53 via p38 MAPK pathway that subsequently causes apoptosis,
      which may be related to sperm parameters. 

PMID- 24313629
TI  - Photoprotection and vitamin D: a review.
AB  - The topic of vitamin D is at the forefront of discussions due to evidence
      suggesting its role in extra-skeletal health. It is already established that
      vitamin D plays a key role in skeletal health in young and elderly adults. This
      vitamin is obtained mainly through sunlight; various factors such as skin
      pigmentation and seasons affect cutaneous synthesis. Debates about the effects of
      sunscreen use on cutaneous synthesis of vitamin D have arisen in recent years. An
      updated review of the literature emphasizes that adequate levels of vitamin D are
      needed to prevent osteoporosis, falls and fractures in the elderly population.
      Emerging data also point to its role in cardiovascular disease, auto-immune
      conditions and cancers. Normal usage of sunscreen by adults has not shown to
      decrease cutaneous synthesis of vitamin D. Recommended Daily Allowance for
      vitamin D, released in 2010, was based on studies examining skeletal effects of
      this vitamin. Oral intake with vitamin d-enriched foods or vitamin D supplements
      is recommended over prolonged ultraviolet exposure to maintain proper serum
      levels. Patients should not be discouraged from normal usage of sunscreens due to
      their well-established photoprotective effects.

PMID- 24313630
TI  - Automatic scoring of sleep stages and cortical arousals using two electrodes on
      the forehead: validation in healthy adults.
AB  - Accuracy and limitations of automatic scoring of sleep stages and
      electroencephalogram arousals from a single derivation (Fp1 -Fp2 ) were studied
      in 29 healthy adults using a portable wireless polysomnographic recorder. All
      recordings were scored five times: twice by a referent scorer who viewed the
      standard polysomnographic montage and observed the American Academy of Sleep
      Medicine rules (referent scoring and blind rescoring); and once by the same
      scorer who viewed only the Fp1 -Fp2 signal (alternative scoring), by another
      expert from the same institution, and by the algorithm. Automatic, alternative
      and independent expert scoring were compared with the referent scoring on an
      epoch-by-epoch basis. The algorithm's agreement with the reference (81.0%,
      Cohen's kappa = 0.75) was comparable to the inter-rater agreement (83.3%, Cohen's
      kappa = 0.78) or agreement between the referent scoring and manual scoring of the
      frontopolar derivation (80.7%, Cohen's kappa = 0.75). Most misclassifications by
      the algorithm occurred during uneventful wake/sleep transitions, whereas cortical
      arousals, rapid eye movement and stable non-rapid eye movement sleep were
      detected accurately. The algorithm yielded accurate estimates of total sleep
      time, sleep efficiency, sleep latency, arousal indices and times spent in
      different stages. The findings affirm the utility of automatic scoring of stages
      and arousals from a single frontopolar derivation as a method for assessment of
      sleep architecture in healthy adults. 

PMID- 24313631
TI  - The relationship between daily hassles and sexual function in men and women.
AB  - Psychological stressors can interfere with sexual function through psychological
      and physiological mechanisms. Chronic stress, in particular, seems to have a
      negative effect on sexual functioning for men and women. The present study was
      designed to identify categories of stressors that contribute to sexual
      difficulties as well as assess the role of anxiety and depression in the
      relationship between stress and sexual function. Participants were recruited for
      an online survey in which they completed questionnaires on daily stressors,
      anxiety, depression, and sexual function. Results indicated that daily stressors
      predicted lower scores on sexual satisfaction for men and women and sexual
      activity for women. These effects were mediated by scores on the depression
      scale. Daily stressors, depression, and anxiety were highly correlated. A factor
      analysis of stressors resulted in 5 distinct categories of stressors. Of these,
      financial stressors and stressors related to low socioeconomic status were
      related to lower scores on all aspects of sexual functioning for women but not
      for men. Women's sexual functioning scores were more strongly related to stress
      and depression than men's scores. Results suggest that contextual factors (e.g.,
      daily stressors, depression) are important considerations when assessing problems
      with sexual functioning. 

PMID- 24313632
TI  - Structural correlates of cognitive deficit and elevated gamma noise power in
      schizophrenia.
AB  - AIMS: The aim of this study was to assess the relation between cognition, gray
      matter (GM) volumes and gamma noise power (amount of background oscillatory
      activity in the gamma band) in schizophrenia. METHODS: We explored the relation
      between cognitive performance and regional GM volumes using voxel-based
      morphometry (VBM), in order to discover if the association between gamma noise
      power (an electroencephalography measurement of background activity in the gamma
      band) and cognition is observed through structural deficits related to the
      disease. Noise power, magnetic resonance imaging and cognitive assessments were
      obtained in 17 drug-free paranoid patients with schizophrenia and 13 healthy
      controls. RESULTS: In comparison with controls, patients showed GM deficits at
      posterior cingulate (bilateral),left inferior parietal (supramarginal gyrus) and
      left inferior dorsolateral prefrontal regions. Patients exhibited a direct
      association between performance in working memory and right temporal (superior
      and inferior gyri) GM densities. They also displayed a negative association
      between right anterior cerebellum volume and gamma noise power at the frontal
      midline (Fz) site. CONCLUSION: A structural deficit in the cerebellum may be
      involved in gamma activity disorganization in schizophrenia. Temporal structural
      deficits may relate to cognitive dysfunction in this illness.

PMID- 24313633
TI  - An improved dosage regimen of sertraline hydrochloride in the treatment for
      premature ejaculation: an 8-week, single-blind, randomized controlled study
      followed by a 4-week, open-label extension study.
AB  - WHAT IS KNOWN AND OBJECTIVE: This study aimed at evaluating the safety and
      efficacy of an improved dosage regimen of sertraline in patients with premature
      ejaculation (PE) and to examine whether the premature ejaculation diagnostic tool
      (PEDT) can be used as a measure of treatment response in these patients. METHODS:
      A total of 218 PE patients were randomized into control (n = 61) and treatment (n
      = 157) groups to receive mycelium of cordyceps sinensis C4 and sertraline 50 mg
      daily for 8 weeks, respectively. Following this blinded stage, sixty-three
      patients chose to take sertraline 100 mg daily for an additional 4-week period,
      and 80 other patients continued treatment with sertraline 50 mg. Main outcome
      measures include intravaginal ejaculatory latency time (IELT), PEDT score and
      Clinical Global Impression of Change (CGIC) score. RESULTS: At weeks 4 and 8,
      mean IELT of patients who subsequently chose to take 100 mg of sertraline was
      significantly lower than that of patients who continued taking 50 mg of
      sertraline, although the IELT value was comparable between the two groups of
      patients at baseline. However, with an additional 4-week treatment, the mean IELT
      increased significantly more in the 100-mg group than in the 50-mg continuation
      group. Similar results were also obtained in the analyses of the PEDT and CGIC
      scores. Both regimens were well tolerated, and relapse rate did not differ
      significantly between the two groups. WHAT IS NEW AND CONCLUSION: These findings
      suggest that PE patients not responding to an 8-week treatment with sertraline 50
      mg can benefit from an additional 4-week treatment with sertraline 100 mg and
      that the PEDT may be a valid measure of treatment response in PE patients.

PMID- 24313634
TI  - Spacer intercalated disassembly and photodynamic activity of zinc phthalocyanine
      inside nanochannels of mesoporous silica nanoparticles.
AB  - Hydrophobic photosensitizer zinc(II) phthalocyanine (ZnPc) was loaded into
      adamantane (Ad) modified nanochannels of mesoporous silica nanoparticles (MSNPs).
      The Ad units on the surface of MSNPs were complexed with amino-substituted beta
      cyclodextrin to enhance the solubility of the hybrid in aqueous solution. The
      amino groups on beta-cyclodextrin also provide functional sites for further
      conjugation with targeting ligands toward targeted cancer therapy. Since the
      intercalation of the Ad spacer isolates loaded ZnPc and prevents its aggregation
      inside MSNPs, ZnPc exhibits its monomeric characteristics to effectively generate
      cytotoxic singlet oxygen ((1)O2) upon light irradiation (675 nm) in aqueous
      conditions, leading to efficient photodynamic activity for successful cancer
      treatment in vitro. Current research presents a convenient approach to maintain
      the monomeric state of hydrophobic photosensitizer ZnPc by rationally utilizing
      multifunctional MSNPs as the carriers. The novel hybrid with targeting capability
      achieves active photodynamic property of monomeric ZnPc in aqueous solution under
      light irradiation, which may find its way for practical photodynamic therapy in
      the future.

PMID- 24313635
TI  - Diagnostic delays in children with early onset epilepsy: impact, reasons, and
      opportunities to improve care.
AB  - PURPOSE: Delayed diagnosis of early onset epilepsy is a potentially important and
      avoidable complication in epilepsy care. We examined the frequency of diagnostic
      delays in young children with newly presenting epilepsy, their developmental
      impact, and reasons for delays. METHODS: Children who developed epilepsy before
      their third birthday were identified in a prospective community-based cohort. An
      interval >=1 month from second seizure to diagnosis was considered a delay.
      Testing of development at baseline and for up to 3 years after and of
      intelligence quotient (IQ) 8-9 years later was performed. Detailed parental
      baseline interview accounts and medical records were reviewed to identify
      potential reasons for delays. Factors associated with delays included the parent,
      child, pediatrician, neurologist, and scheduling. RESULTS: Diagnostic delays
      occurred in 70 (41%) of 172 children. Delays occurred less often if children had
      received medical attention for the first seizure (p < 0.0001), previously had
      neonatal or febrile seizures (p = 0.02), had only convulsions before diagnosis (p
      = 0.005), or had a college-educated parent (p = 0.01). A >=1 month diagnostic
      delay was associated with an average 7.4 point drop (p = 0.02) in the Vineland
      Scales of Adaptive Behavior motor score. The effect was present at diagnosis,
      persisted for at least 3 years, and was also apparent in IQ scores 8-9 years
      later, which were lower in association with a diagnostic delay by 8.4 points (p =
      0.06) for processing speed up to 14.5 points (p = 0.004) for full scale IQ, after
      adjustment for parental education and other epilepsy-related clinical factors.
      Factors associated with delayed diagnosis included parents not recognizing events
      as seizures (N = 47), pediatricians missing or deferring diagnosis (N = 15),
      neurologists deferring diagnosis (N = 7), and scheduling problems (N = 11).
      SIGNIFICANCE: Diagnostic delays occur in many young children with epilepsy. They
      are associated with substantial decrements in development and IQ later in
      childhood. Several factors influence diagnostic delays and may represent
      opportunities for intervention and improved care.

PMID- 24313636
TI  - Evaluation of Propess outcomes for cervical ripening and induction of labour in
      full-term pregnancy.
AB  - This study was to investigate the efficiency and safety of vaginal Propess as a
      methodology for cervical ripening and labour induction in full-term pregnant
      patients. Women at term with a Bishop's score of < 6 and without any
      contraindications, to vaginal delivery, or the use of prostaglandin or oxytocin
      in induction of labour, were divided into three groups: oxytocin group (n = 59),
      intact membranes (Propess I group; n = 58) and natural rupture (Propess R group;
      n = 52) groups. The main outcome measures, including change in Bishop's score,
      induction to delivery interval, total delivery time, rate of vaginal delivery,
      fetal outcome and maternal complications during induction, were recorded. In the
      Propess groups, the Bishop's score and rate of vaginal delivery were
      significantly higher while the induction to delivery interval and total delivery
      time were much shorter, as compared with oxytocin patients (p < 0.01). There were
      no significant differences in fetal and maternal outcome during induction between
      the Propess groups and oxytocin group (p > 0.05). In addition, there were no
      significant differences of Bishop's score, rate of vaginal delivery, induction to
      delivery interval and total delivery time between the Propess I group and Propess
      R group (p > 0.05). Propess is an effective and safe approach to promote cervical
      ripening and be successfully used in induction of labour.

PMID- 24313637
TI  - Associative learning of Nasonia vitripennis Walker (Hymenoptera:Pteromalidae) to
      methyldisulfanylmethane.
AB  - Traditional methods of volatile detection used by police typically consist of
      reliance on canine olfaction. However, dogs have some limitations such as cost of
      training and time of conditioning. The possibility of using parasitic wasps for
      detecting explosives and narcotics has been developed. Moreover, wasps are cheap
      to produce and can be conditioned with impressive speed for a specific chemical
      detection task. We examined the ability of Nasonia vitripennis Walker to learn
      and respond to methyldisulfanylmethane (DMDS), a volatile discriminator of
      cadaver. The training aimed to form an association between an unconditioned
      stimulus (pupae) and the conditioned stimulus (odor source). After the training,
      the time spent by conditioned wasps in the DMDS chamber was measured. Statistical
      analysis showed that the increasing concentrations involved an increase in the
      time spent in the chamber containing DMDS. This study indicates that N.
      vitripennis can respond to DMDS, which provide further support for its
      development as a biological sensor. 

PMID- 24313638
TI  - Masked priming and ERPs dissociate maturation of orthographic and semantic
      components of visual word recognition in children.
AB  - This study examined the time-course of reading single words in children and
      adults using masked repetition priming and the recording of event-related
      potentials. The N250 and N400 repetition priming effects were used to
      characterize form- and meaning-level processing, respectively. Children had
      larger amplitude N250 effects than adults for both shorter and longer duration
      primes. Children did not differ from adults on the N400 effect. The difference on
      the N250 suggests that automaticity for form processing is still maturing in
      children relative to adults, while the lack of differentiation on the N400 effect
      suggests that meaning processing is relatively mature by late childhood. The
      overall similarity in the children's repetition priming effects to adults'
      effects is in line with theories of reading acquisition, according to which
      children rapidly transition to an orthographic strategy for fast access to
      semantic information from print.

PMID- 24313639
TI  - A 36-month study of patient complaints at a tertiary fertility centre.
AB  - Patient satisfaction is an integral component of measuring health care quality.
      Attention to patient complaints is part of a strategy to resolve dissatisfaction
      and improve care. Our aim was to review patient complaints in a UK fertility
      centre, and their outcome. Data regarding all complaints made to the fertility
      services over 3 years, the outcome and actions implemented were collected
      retrospectively. Between 2008 and 2011, the fertility unit received 27 (6%)
      complaints from a total of 450 complaints for the entire Trust (NHS hospital).
      Complaints could be categorised as Primary Care Trust (funding body) (PCT) (n =
      7) and non PCT related (n = 20). Most PCT complaints related to funding
      restrictions imposed by the PCT. The majority of complaints (n = 20) related to
      the fertility services and most complaints were multifactorial. Of the total,
      communication errors and administrative delays accounted for 19 out of 27
      complaints, the remainder being due to staff attitude and direct clinical care
      issues. Of the 27, 25 (93%) were satisfied with a written response and only 2
      required a further meeting; 67% of complaints were settled with an apology or
      explanation alone (18/27), while 30% (8/27) required a review of policy. Improved
      communication with patients, General Practitioners and commissioners should
      reduce complaints. The resolution of the majority of complaints can be achieved
      locally and should be used in a positive way to improve patient care.

PMID- 24313640
TI  - Long-term effect of hormone therapy on bone in early menopause: vertebral
      fractures after 20 years.
AB  - OBJECTIVE: The role of menopausal hormone therapy (HT) on vertebral fracture
      prevention after treatment discontinuation is controversial. The aim of this
      study was to assess the incidence of vertebral fracture in a group of women who
      received HT in early menopause compared with another group who did not receive
      such treatment after 20 years of follow-up. SUBJECTS AND METHODS: In 1990, we
      included 177 patients aged 43-57 years old (mean 49.1 +/- 3.9 years) in a
      prospective study to evaluate the effect of different HT regimens on bone
      metabolism and mineral density. After 20-21 years, a total of 49 patients from
      the initial study were retrieved. These patients were divided into two groups:
      the first group included women who had taken HT, and those who constituted the
      control groups and had not taken HT formed the second group. Clinical and
      demographic data were analyzed and vertebral fracture was assessed by radiology
      using the Genant semiquantitative scale. RESULTS: Of the 49 patients enrolled, 32
      (65.3%) received HT for an average of 5.5 (+/- 2.96) years while the 17 (34.7%)
      remaining belonged to the control group without treatment. A higher rate of
      vertebral fracture was observed in the group receiving HT (p = 0.03). Depending
      on the degree of fracture (Genant semiquantitative method), subsequent analysis
      by subgroups corroborated the higher rate in the group receiving HT in all cases
      (p < 0.05). Multivariate analysis ruled out the effect of the clinical and
      demographic variables (current age, age at menopause, body mass index, type of
      menopause and drugs for the treatment of osteoporosis) in the final result.
      CONCLUSION: In spite of the fact that this study does not have a large enough
      sample, our data suggest that HT used in the early years of menopause does not
      present a long-term protective effect on vertebral fracture after discontinuing
      treatment.

PMID- 24313641
TI  - Can lipoprotein-associated phospholipase A2 be used as a predictor of long-term
      outcome in patients with acute coronary syndrome?
AB  - Studies indicate that elevated plasma concentrations of lipoprotein-associated
      phospholipase A2 (Lp-PLA2) is associated with increased risk of cardiovascular
      disease. Lp-PLA2 seems to play a crucial role in the formation of plaques and
      acute inflammation, and plasma Lp-PLA2 could therefore potentially be used as a
      predictor of long-term outcome in ACS patients. To evaluate this, data concerning
      Lp-PLA2 as a predictor in ACS patients was gathered through a systematic
      literature review, and studies on this issue were extracted from relevant
      databases, incl. PubMed and Cochrane. A total of 14 articles were retrieved, but
      after thorough evaluation and elimination of irrelevant articles only seven
      studies were eligible for the literature review. All studies except two showed
      significant correlation between Lp-PLA2 and CV events in ACS patients. Only one
      study found an independent value to predict CV events 30 days after ACS.
      Altogether, there was inconsistency in the findings regarding the potential use
      of Lp-PLA2 and a lack of knowledge on several issues. Lp-PLA2 seems to give
      valuable information on which ACS patients are prone to new events and also
      provides important information on plaque size. However, more focused studies
      concerning genetic variations, time-window impact, patients with and without CV
      risk factors (e.g. diabetes), and treatment effects are needed. In conclusion, Lp
      PLA2 offers new insight in the pathophysiological development of ACS, but until
      the aforementioned issues are addressed the biomarker will mainly be of interest
      in a research setting, not as a predictive parameter in a clinical setting. 

PMID- 24313642
TI  - Infective endocarditis complicating hypertrophic obstructive cardiomyopathy: is
      antibiotic prophylaxis really unnecessary?
AB  - Infective endocarditis is a relatively rare complication of hypertrophic
      cardiomyopathy. Infective endocarditis in hypertrophic cardiomyopathy is almost
      always seen in patients with outflow obstruction and is more common in those with
      both outflow obstruction and atrial dilatation. We present a case of culture
      negative mitral valve endocarditis in a previously asymptomatic woman with
      hypertrophic cardiomyopathy who died in the course of the disease. 

PMID- 24313643
TI  - Basal septal hypertrophy.
AB  - A significant clinical problem is patients presenting with exercise-limiting
      dyspnoea, sometimes with associated chest pain, in the absence of detectable left
      ventricular (LV) systolic dysfunction, coronary artery disease, or lung disease.
      Often the patients are older, female, and have isolated basal septal hypertrophy
      (BSH), frequently on a background of mild hypertension. The topic of
      breathlessness in patients with clinical heart failure, but who have a normal
      ejection fraction (HFNEF) has attracted significant controversy over the past few
      years. This review aims to analyse the literature on BSH, identify the possible
      associations between BSH and HFNEF, and consequently explore possible
      pathophysiological mechanisms whereby clinical symptoms are experienced. 

PMID- 24313644
TI  - Recent advances in transcatheter aortic valve implantation: novel devices and
      potential shortcomings.
AB  - During the past years transcatheter aortic valve implantation (TAVI) has evolved
      to a standard technique for the treatment of high risk patients suffering from
      severe aortic stenosis. Worldwide the number of TAVI procedures is increasing
      exponentially. In this context both the transapical antegrade (TA) and the
      transfemoral retrograde (TF) approach are predominantly used and can be
      considered as safe and reproducible access sites for TAVI interventions. As a new
      technology TAVI is in a constant progress regarding the development of new
      devices. While in the first years only the Edwards SAPIEN(TM) and the Medtronic
      CoreValve(TM) prostheses were commercial available, recently additional devices
      obtained CE-mark approval and others have entered initial clinical trials. In
      addition to enhance the treatment options in general, the main driving factor to
      further develop new device iterations is to solve the drawbacks of the current
      TAVI systems: paravalvular leaks, occurrence of AV-blocks and the lack of full
      repositionability. 

PMID- 24313645
TI  - Long-term results after transcatheter aortic valve implantation: what do we know
      today?
AB  - Transcatheter aortic valve implantation (TAVI) is evolving rapidly as a
      therapeutic option in patients deemed to be at high risk for surgical aortic
      valve replacement. Early outcome and survival of controlled feasibility trials
      and single- center experience with TAVI have been previously reported. Valve
      performance and hemodynamics seem to improve significantly after TAVI. Long-term
      outcome up to 3 years have been demonstrated in recent studies. Admittedly, the
      results are encouraging with a survival rate at 2 and 3 years ranging from 62 to
      74% and from 56 to 61% respectively. The improvement in hemodynamical and
      clinical status sustained beyond the 3 years follows up. However, paravalvular
      leakage after TAVI remains an important issue in this rapidely evolving field. 

PMID- 24313646
TI  - Transcatheter Heart Valves: Specific Characteristics and Potential Shortcomings.
AB  - During the past years TAVI has evolved to a standard technique for the treatment
      of high risk patients suffering from severe aortic stenosis. Worldwide the number
      of TAVI procedures is increasing exponentially. In this context both the
      transapical antegrade (TA) and the transfemoral retrograde (TF) approach are
      predominantly used and can be considered as safe and reproducible access sites
      for TAVI interventions. As a new technology TAVI is in a constant progress
      regarding the development of new devices. While in the first years only the
      Edwards SAPIENTM and the Medtronic CoreValveTM prostheses were commercial
      available, recently additional devices obtained CE-mark approval and others have
      entered initial clinical trials. In addition to enhance the treatment options in
      general, the main driving factor to further develop new device iterations is to
      solve the drawbacks of the current TAVI systems: paravalvular leaks, occurrence
      of AV-blocks and the lack of full repositionability.

PMID- 24313647
TI  - Which way in? The necessity of multiple approaches to transcatheter valve
      therapy.
AB  - TAVI (transcatheter aortic valve implantation) is a less invasive treatment of
      the stenotic aortic valve while avoiding midline sternotomy and cardiopulmonary
      bypass. A crimped biological valve on a self-expanding or balloonexpandable stent
      is inserted antegradely or retrogradely under fluoroscopy, and deployed on the
      beating heart. Among the worldwide TAVI programs, many different concepts have
      been established for the choice of the access site. Whether retrograde or
      antegrade TAVI should be considered the superior approach is matter of an ongoing
      debate. The published literature demonstrates safety of all techniques if
      performed within a dedicated multidisciplinary team. Since there is no data
      providing evidence if one approach is superior to another, we conclude that an
      individualized patient-centered decision making process is most beneficial,
      taking advantage of the complementarity of the different access options. The aim
      of this article is to give an overview of the current practice of access
      techniques for transcatheter based valve treatment and to outline the respective
      special characteristics. 

PMID- 24313649
TI  - Transcatheter aortic valve implantation.

PMID- 24313648
TI  - Beyond adding years to life: health-related quality-of-life and functional
      outcomes in patients with severe aortic valve stenosis at high surgical risk
      undergoing transcatheter aortic valve replacement.
AB  - Aortic valve stenosis (AVS) is the most frequent acquired valvular heart disease
      in western industrialized countries and its prevalence considerably increases
      with age. Once becoming symptomatic severe AVS has a very poor prognosis.
      Progressive and rapid symptom deterioration leads to an impairment of functional
      status and compromised healthrelated quality-of-life (HrQoL) simultaneously.
      Until recently, surgical aortic valve replacement (SAVR) has been the only
      effective treatment option for improving symptoms and prolonging survival.
      Transcatheter aortic valve replacement (TAVR) emerged as an alternative treatment
      modality for those patients with severe symptomatic AVS in whom the risk for SAVR
      is considered prohibitive or too high. TAVR has gained clinical acceptance with
      almost startling rapidity and has even quickly become the standard of care for
      the treatment of appropriately selected individuals with inoperable AVS during
      recent years. Typically, patients currently referred for and treated by TAVR are
      elderly with a concomitant variable spectrum of multiple comorbidities,
      disabilities and limited life expectancy. Beyond mortality and morbidity, the
      assessment of HrQoL is of paramount importance not only to guide patient-centered
      clinical decision-making but also to judge this new treatment modality. As per
      current evidence, TAVR significantly improves HrQoL in high-surgical risk
      patients with severe AVS with sustained effects up to two years when compared
      with optimal medical care and demonstrates comparable benefits relative to SAVR.
      Along with a provision of a detailed overview of the current literature regarding
      functional and HrQoL outcomes in patients undergoing TAVR, this review article
      addresses specific considerations of the HrQoL aspect in the elderly patient and
      finally outlines the implications of HrQoL outcomes for medico-economic
      deliberations. 

PMID- 24313650
TI  - Dysfunctional and compensatory synaptic plasticity in Parkinson's disease.
AB  - In Parkinson's disease, a loss of dopamine neurons causes severe motor
      impairments. These motor impairments have long been thought to result exclusively
      from immediate effects of dopamine loss on neuronal firing in basal ganglia,
      causing imbalances of basal ganglia pathways. However, motor impairments and
      pathway imbalances may also result from dysfunctional synaptic plasticity - a
      novel concept of how Parkinsonian symptoms evolve. Here we built a neuro
      computational model that allows us to simulate the effects of dopamine loss on
      synaptic plasticity in basal ganglia. Our simulations confirm that dysfunctional
      synaptic plasticity can indeed explain the emergence of both motor impairments
      and pathway imbalances in Parkinson's disease, thus corroborating the novel
      concept. By predicting that dysfunctional plasticity results not only in reduced
      activation of desired responses, but also in their active inhibition, our
      simulations provide novel testable predictions. When simulating dopamine
      replacement therapy (which is a standard treatment in clinical practice), we
      observe a new balance of pathway outputs, rather than a simple restoration of non
      Parkinsonian states. In addition, high doses of replacement are shown to result
      in overshooting motor activity, in line with empirical evidence. Finally, our
      simulations provide an explanation for the intensely debated paradox that focused
      basal ganglia lesions alleviate Parkinsonian symptoms, but do not impair
      performance in healthy animals. Overall, our simulations suggest that the effects
      of dopamine loss on synaptic plasticity play an essential role in the development
      of Parkinsonian symptoms, thus arguing for a re-conceptualisation of Parkinsonian
      pathophysiology.

PMID- 24313651
TI  - Phosphinecarboxamide: a phosphorus-containing analogue of urea and stable primary
      phosphine.
AB  - Reactions of the 2-phosphaethynolate anion (PCO(-), 1) with ammonium salts
      quantitatively yielded phosphinecarboxamide (PH2C(O)NH2, 2). The molecular
      structure and chemical properties of 2 were studied by single-crystal X-ray
      diffraction and multielement NMR spectroscopy. This phosphorus-containing
      analogue of urea is a rare example of an air-stable primary phosphine. 

PMID- 24313652
TI  - Classifying squamous cell carcinoma of the head and neck: prognosis, prediction
      and implications for therapy.
AB  - Traditionally, squamous cell cancers of the head and neck (SCCHN) have been
      classified by their anatomic location and stage. This system has been
      unsatisfactory in that it leaves substantial heterogeneity in prognosis and
      inadequate definition of optimal therapy. The most promising novel marker for
      superior prognosis in SCCHN is human papillomavirus (HPV). Overexpression of the
      EGFR bears an adverse prognosis; no marker provides clear predictive power for
      benefit from EGFR inhibition. Low expression of the DNA repair enzymes and
      excision repair cross-complementing rodent repair deficiency (ERCC1) and x-ray
      repair complementing defective repair in Chinese hamster cells 1 (XRCC1) may
      predict chemotherapy and chemoradiotherapy sensitivity. Tumors expressing cyclin
      D1 have a poor prognosis. Genomic characterization has subdivided SCCHN into four
      categories with clear biologic themes. Basal cancers express high levels of TGF
      alpha and have other perturbations of the EGFR axis. Mesenchymal cancers show
      evidence for epithelial to mesenchymal transition. Atypical cancers lack both
      EGFR amplification and deletion of 9p; they also have a higher rate of HPV
      positivity than the other groups. Classical tumors demonstrate gene signatures
      similar to those previously associated with exposure to cigarette smoke; patients
      with this signature had a greater smoking history than patients in the other
      groups. 

PMID- 24313653
TI  - Rapid photooxidation of As(III) through surface complexation with nascent
      colloidal ferric hydroxide.
AB  - Contamination of water and soils with arsenic, especially inorganic arsenic, has
      been one of the most important topics in the fields of environmental science and
      technology. The interactions between iron and arsenic play a very significant
      role in the environmental behavior and effect of arsenic species. However, the
      mechanism of As(III) oxidation in the presence of iron has remained unclear
      because of the complicated speciation of iron and arsenic. Photooxidation of
      As(III) on nascent colloidal ferric hydroxide (CFH) in aqueous solutions at pH 6
      was studied to reveal the transformation mechanism of arsenic species.
      Experiments were done by irradiation using light-emitting diodes with a central
      wavelength of 394 nm. Results show that photooxidation of As(III) and
      photoreduction of Fe(III) occurred simultaneously under oxic or anoxic
      conditions. Photooxidation of As(III) in the presence of nascent CFH occurred
      through electron transfer from As(III) to Fe(III) induced by absorption of
      radiation into a ligand-to-metal charge-transfer (LMCT) band. The estimated
      quantum yield of photooxidation of As(III) at 394 nm was (1.023 +/- 0.065) * 10(
      2). Sunlight-induced photooxidation of As(III) also occurred, implying that
      photolysis of the CFH-As(III) surface complex could be an important process in
      environments wherein nascent CFH exists. 

PMID- 24313654
TI  - Origin of Langerhans cells in normal skin and chronic GVHD after hematopoietic
      stem-cell transplantation.
AB  - Chronic graft-versus-host disease (cGVHD) is a common complication following
      allogeneic stem-cell transplantation (SCT). Past studies have implicated the
      persistence of host antigen-presenting cells (APCs) in GVHD. Our objective was to
      determine the frequency of host Langerhans cells (LCs) in normal skin post-SCT
      and ask if their persistence could predict cGVHD. Biopsies of normal skin from
      124 sex-mismatched T-cell-replete allogenic SCT recipients were taken 100 days
      post-transplant. Patients with acute GVHD and those with <9 months of follow-up
      were excluded and prospective follow-up information was collected from remaining
      22 patients. CD1a staining and X and Y chromosome in-situ hybridization were
      performed to label LCs and to identify their host or donor origin. At 3 months,
      59 +/- 5% of LCs were host derived. The density of LCs and the proportion of host
      derived LCs were similar between patients that did or did not develop cGVHD. Most
      LCs in the skin remained of host origin 3 months after SCT regardless of cGVHD
      status. This finding is in line with the redundant role of LCs in acute GVHD
      initiation uncovered in recent experimental models.

PMID- 24313655
TI  - Effectiveness of the Bactiseal Universal Shunt for reducing shunt infection in a
      sub-Saharan African context: a retrospective cohort study in 160 Ugandan
      children.
AB  - OBJECT: Antibiotic-impregnated shunts have yet to find widespread use in the
      developing world, largely due to cost. Given potential differences in the
      microbial spectrum, their effectiveness in preventing shunt infection for
      populations in low-income countries may differ and has not been demonstrated.
      This study is the first to compare the efficacy of a Bactiseal shunt system with
      a non-antibiotic-impregnated system in a developing country. METHODS: The
      Bactiseal Universal Shunt (BUS) was placed in 80 consecutive Ugandan children who
      required a shunt. In this retrospective cohort study, the outcome for that group
      was compared with the outcome for the immediately preceding 80 consecutive
      children in whom a Chhabra shunt had been placed. The primary end points were
      shunt failure, shunt infection, and death. Shunt survival was analyzed using the
      Kaplan-Meier method. Significance of differences between groups was tested using
      the log-rank test, chi-square analysis, Fisher's exact test, and t-test. RESULTS:
      There was no difference between groups in regard to age, sex, or etiology of
      hydrocephalus. Mean follow-up for cases of nonfailure was 7.6 months (median 7.8
      months, interquartile range 6.5-9.5 months). There was no significant difference
      between groups for any end point. The BUS group had fewer infections (4 vs 11),
      but the difference was not significant (p = 0.086, log-rank test). Gram-positive
      cocci were the most common culturable pathogens in the Chhabra group, while the
      only positive culture in the BUS group was a gram-negative rod. CONCLUSIONS:
      These results provide equipoise for a randomized controlled trial in the same
      population and this has been initiated. It is possible that the observed trends
      may become significant in a larger study. The more complex task will involve
      determining not only the efficacy, but also the cost-effectiveness of using
      antibiotic-impregnated shunt components in limited-resource settings.

PMID- 24313656
TI  - Bone flap resorption in infants.

PMID- 24313657
TI  - Hydrocephalus research funding from the National Institutes of Health: a 10-year
      perspective.
AB  - OBJECT: Funding of hydrocephalus research is important to the advancement of the
      field. The goal of this paper is to describe the funding of hydrocephalus
      research from the National Institutes of Health (NIH) over a recent 10-year
      period. METHODS: The NIH online database RePORT (Research Portfolio Online
      Reporting Tools) was searched using the key word "hydrocephalus." Studies were
      sorted by relevance to hydrocephalus. The authors analyzed funding by institute,
      grant type, and scientific approach over time. RESULTS: Over $54 million was
      awarded to 59 grantees for 66 unique hydrocephalus proposals from 48 institutions
      from 2002 to 2011. The largest sources of funding were the National Institute of
      Neurological Disease and Stroke and the National Institute of Child Health and
      Human Development. Of the total, $22 million went to clinical trials, $15 million
      to basic science, and $10 million to joint ventures with small business (Small
      Business Innovation Research or Small Business Technology Transfer). Annual
      funding varied from $2.3 to $8.1 million and steadily increased in the second
      half of the observation period. The number of new grants also went from 15 in the
      first 5 years to 27 in the second 5 years. A large portion of the funding has
      been for clinical trials. Funding for shunt-device development grew
      substantially. Support for training of hydrocephalus investigators has been low.
      CONCLUSIONS: Hydrocephalus research funding is low compared with that for other
      conditions of similar health care burden. In addition to NIH applications,
      researchers should pursue other funding sources. Small business collaborations
      appear to present an opportunity for appropriate projects.

PMID- 24313658
TI  - Impact of skull base development on endonasal endoscopic surgical corridors.
AB  - OBJECT: Scarce morphometric data exist on the developing skull base as a corridor
      for endonasal endoscopic approaches (EEAs). Furthermore, the impact of skull base
      lesions on its development has not been assessed. The authors describe a novel
      set of anatomical parameters characterizing the developmental process as well as
      the utility of these parameters in preoperative planning and a feasibility
      assessment of EEAs for neurosurgical treatment of skull base lesions in children.
      METHODS: Based on specific MRI sequences in 107 pediatric patients (2-16 years of
      age) without skull base lesions (referred to here as the normal population), 3
      sets of anatomical parameters were analyzed according to age group and sex:
      drilling distance, restriction sites, and working distance parameters. A separate
      set of patients undergoing EEAs was analyzed in similar fashion to address the
      impact of skull base lesions on the developmental process. RESULTS: The volume of
      the sphenoid sinus significantly increases with age, reaching 6866.4 mm(3) in the
      14-16 years age group, and directly correlates with the pneumatization type (r =
      0.533, p = 0.0001). The pneumatization process progresses slowly in a temporal
      posterior direction, as demonstrated by the growth trend of the sellar width (r =
      0.428, p = 0.0001). Nasal restriction sites do not change significantly with age,
      with little impact on EEAs. The intercarotid distance is significantly different
      only in the extreme age groups (3.9 mm, p = 0.038), and has an important impact
      on the transsphenoidal angle and the intracranial dissection limits (r = 0.443, p
      < 0.0001). The 14.9 degrees  transsphenoidal angle at 2-4 years has a 37.6%
      significant increase in the 11-13 years age group (p = 0.001) and is highly
      dependent on pneumatization type. Age-dependent differences between working
      parameters are mostly noted for the extreme age groups, such as the 8.6-mm
      increase in nare-vomer distance (p = 0.025). The nare-sellar distance is the only
      parameter with significant differences based on sex. Skull base lesions induce a
      high degree of variance in skull base measurements, delaying development and
      decreasing parameter values. Skull base parameters are interdependent. Nare
      sellar distance can be used to assess global skull base development because it
      highly correlates with the intercarotid distance in both the normal population
      and in patients harboring skull base lesions. CONCLUSIONS: Skull base development
      is a slow, gradual, age-dependent, sex-independent process significantly altering
      endonasal endoscopic corridors. Preoperative MRI measurements of the pediatric
      skull base are thus a useful adjunct in choosing the appropriate corridor and in
      assessing working angles and limits during dissection or reparative surgery.
      Skull base lesions can significantly impact normal skull base development and age
      dependent growth patterns.

PMID- 24313659
TI  - Comparative effectiveness of treatment options for pediatric craniopharyngiomas.
AB  - OBJECT: No clear treatment guidelines for pediatric craniopharyngiomas exist. The
      authors developed a decision analytical model to evaluate outcomes of 4 surgical
      approaches for craniopharyngiomas in children, including attempted gross-total
      resection (GTR), planned subtotal removal plus radiotherapy, biopsy plus
      radiotherapy, and endoscopic resections of all kinds. METHODS: Pooled data,
      including the authors' own experience, were used to create evidence tables, from
      which incidence, relative risks, and summary outcomes in quality-adjusted life
      years (QALYs) were calculated for the 4 management strategies. RESULTS: Quality
      adjusted life years at the 5-year follow-up were 2.3 +/- 0.1 for attempted GTR,
      2.9 +/- 0.2 for planned subtotal removal plus radiotherapy, 3.9 +/- 0.2 for
      biopsy plus radiotherapy, and 3.7 +/- 0.2 for endoscopic resection (F = 17,150, p
      < 0.001). Similarly, QALYs at 10-year follow-up were 4.5 +/- 0.2 for attempted
      GTR, 5.7 +/- 0.5 for planned subtotal removal plus radiotherapy, and 7.8 +/- 0.5
      for biopsy plus radiotherapy (F = 6,173, p < 0.001). On post hoc pairwise
      comparisons, the differences between all pairs compared were also highly
      significant (p < 0.001). Since follow-up data at 10 years are lacking for
      endoscopic cases, this category was excluded from 10-year comparisons.
      CONCLUSIONS: Biopsy with subsequent radiotherapy is the preferred approach with
      respect to improved overall quality of life. While endoscopic approaches also
      show promise in preserving quality of life at five-year follow-up, there are not
      sufficient data to draw conclusions about this comparison at 10 years.

PMID- 24313661
TI  - The protective effect of Kaempferia parviflora extract on UVB-induced skin
      photoaging in hairless mice.
AB  - BACKGROUND: Chronic skin exposure to ultraviolet (UV) light increases reactive
      oxygen species (ROS) and stimulates the expression of matrix metalloproteinases
      (MMPs) through c-Jun and c-Fos activation. These signaling cascades induce the
      degradation of extracellular matrix (ECM) components, resulting in photoaging.
      METHODS: This study evaluated the preventive effect of the ethanol extract of
      Kaempferia parviflora Wall. ex. Baker (black ginger) on UVB-induced photoaging in
      vivo. To investigate the antiphotoaging effect of K. parviflora extract (KPE),
      UVB-irradiated hairless mice administered oral doses of KPE (100 or 200
      mg/kg/day) for 13 weeks. RESULTS: In comparison to the UVB control group, KPE
      significantly prevented wrinkle formation and the loss of collagen fibers with
      increased type I, III, and VII collagen genes (COL1A1, COL3A1, and COL7A1). The
      decrease in wrinkle formation was associated with a significant reduction in the
      UVB-induced expression of MMP-2, MMP-3, MMP-9, and MMP-13 via the suppression of
      c-Jun and c-Fos activity. KPE also increased the expression of catalase, which
      acts as an antioxidant enzyme in skin. In addition, expression of inflammatory
      mediators, such as nuclear factor kappa B (NF-kappaB), interleukin-1beta (IL
      1beta), and cyclooxygenase-2 (COX-2), was significantly reduced by KPE treatment.
      CONCLUSION: The results show that oral administration of KPE significantly
      prevents UVB-induced photoaging in hairless mice, suggesting its potential as a
      natural antiphotoaging material.

PMID- 24313660
TI  - Taxonomic revision of the cellulose-degrading fungus Acremonium cellulolyticus
      nomen nudum to Talaromyces based on phylogenetic analysis.
AB  - The cellulase-producing fungal strain Y-94, isolated in Japan and invalidly
      described as Acremonium cellulolyticus nom. nud. strain Y-94, seldom forms
      enteroarthric conidia under nutrient starvation conditions. Phylogenetic analysis
      using ITS1-5.8S-ITS2 and RNA polymerase II large subunit gene sequences revealed
      that strain Y-94 is closely related to Talaromyces, given that these Y-94
      sequences showed 100% identity with those of Talaromyces pinophilus NBRC 100533T
      . By contrast, the identity between beta-tubulin-encoding genes from strain Y-94
      and T. pinophilus NBRC 100533T was 98.1%. Morphological and phenotypic
      differences between these strains in colony color, conidiophore formation, and
      cellulase productivity were observed. Together, these data indicated that strain
      Y-94 belonged to the genus Talaromyces. We propose that strain Y-94 is a new
      species, Talaromyces cellulolyticus, on the basis of morphology and molecular
      evidence. The ex-holotype is Y-94 (= FERM BP-5826, CBS 136886 [holotype] TNS-F
      48752).

PMID- 24313662
TI  - Male reproductive hormone profile in Rwandan students.
AB  - To illustrate the male reproductive hormone profile, a study was conducted among
      healthy male university students living at Butare, Rwanda (altitude: 1 768 m,
      barometric pressure: 629 mm Hg). Venous blood was collected in the morning, after
      overnight fasting. Hormonal assays were performed by classical sandwich ELISA
      technique. Mean values (+/-standard deviation SD) were follicle-stimulating
      hormone FSH: 3.7 +/- 1.6 IU l(-1) ; luteinising hormone LH: 3.6 +/- 2.2 IU l(-1)
      ; and total testosterone: 21.0 +/- 7.5 nm. The results compare well with findings
      of other studies. 

PMID- 24313663
TI  - The effect of brief functional relaxation on college students' needle anxiety
      during injected vaccinations.
AB  - OBJECTIVE: This study examined the effect of brief functional relaxation (FR)
      training on needle anxiety (NA) during vaccinations. PARTICIPANTS: From October
      2010 through May 2012, 48 undergraduates were recruited through the psychology
      research participant pool. METHODS: Students (N = 48) were randomly assigned to a
      15-minute brief FR session delivered via MP3 player or a standard care condition
      (15 minutes of sitting quietly) prior to receiving injections at the immunization
      clinic. Measures were completed before (T1) and after (T2) the assigned
      condition, assessing expected NA, state anxiety, blood pressure, and heart rate;
      and after the injection (T3), self-reported NA during the injection. RESULTS:
      Unexpectedly, the groups did not differ at T2. However, during the injection,
      brief FR participants indicated lower self-reported NA (T3) than standard care.
      CONCLUSIONS: Brief FR is a simple, inexpensive technique that may reduce NA in
      college health settings and help decrease delays in treatment seeking.

PMID- 24313664
TI  - Insomnia symptoms and subsequent cardiovascular medication: a register-linked
      follow-up study among middle-aged employees.
AB  - Sleep disturbances have been associated with an increased risk of cardiovascular
      disease outcomes. The associations of insomnia with hypertension and
      dyslipidaemia, the main modifiable cardiovascular risk factors, are less studied.
      We especially lack understanding on the longitudinal effects of insomnia on
      dyslipidaemia. We aimed to examine the associations of insomnia symptoms with
      subsequent prescribed medication for hypertension and dyslipidaemia using
      objective register-based follow-up data. Baseline questionnaire surveys among 40
      60-year-old employees of the City of Helsinki, Finland, were conducted in 2000
      2002 (n = 6477, response rate 67%, 78% women) and linked to a national register
      on prescribed reimbursed medication 5-7 years prior to and 5 years after
      baseline. Associations between the frequency of insomnia symptoms (difficulties
      in initiating and maintaining sleep, non-restorative sleep) and hypertension and
      dyslipidaemia medication during the follow-up were analysed using logistic
      regression analysis (odds ratios with 95% confidence intervals). Analyses were
      adjusted for pre-baseline medication, sociodemographic and work-related factors,
      health behaviours, mental health, and diabetes. Frequent insomnia symptoms were
      reported by 20%. During the 5-year follow-up, 32% had hypertension medication and
      15% dyslipidaemia medication. Adjusting for age, gender and pre-baseline
      medication, frequent insomnia symptoms were associated with hypertension
      medication (odds ratio 1.57, 95% confidence interval 1.23-2.00) and dyslipidaemia
      medication (odds ratio 1.59, 95% confidence interval 1.19-2.12). Occasional
      insomnia symptoms were also associated with cardiovascular medication, though
      less strongly. Further adjustments had negligible effects. To conclude, insomnia
      should be taken into account in the prevention and management of cardiovascular
      disease and related risk factors. 

PMID- 24313665
TI  - Relationship between blood levels of propofol and recovery of memory in
      electroconvulsive therapy.
AB  - AIM: Memory impairment is a potential major adverse effect of electroconvulsive
      therapy (ECT). Some reports have suggested that propofol, an intravenous
      anesthetic widely used for general anesthesia in ECT, can minimize adverse
      effects on memory and cognitive function following ECT. The relation between
      propofol blood level during ECT and memory impairment after the procedure is
      unknown. We aimed to determine the relation between predicted blood level of
      propofol administered by target-controlled infusion during ECT and memory
      impairment after the procedure. METHODS: Thirty-six patients who underwent a
      total of 260 series of ECT were enrolled as subjects. Anesthesia was induced with
      intravenous injection of propofol with a target-controlled infusion pump for
      predicting blood levels. Orientation and memory testing were performed after
      completion of ECT. In a subsequent analysis, subjects were divided into early
      memory recovery (n = 195) and late memory recovery (n = 65) groups. Likewise, for
      orientation testing,subjects were divided into early recovery (n = 193) and late
      recovery (n = 67) groups. In both groups, predicted blood propofol levels, total
      propofol dose, and other variables, such as number of ECT treatments, stimulus
      energy volume, and spike and slow wave time, were determined for comparison.
      RESULTS: Predicted blood propofol levels and propofol total dose were
      significantly higher in the early memory recovery group, while no significant
      differences were observed for the other variables. As for orientation, there were
      no significant differences between the early and late orientation recovery
      groups. CONCLUSIONS: Our data shows that the predicted blood propofol levels and
      the total dose influences memory impairment after the ECT.

PMID- 24313667
TI  - Brominated flame retardants in breast milk and behavioural and cognitive
      development at 36 months.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent flame
      retardants found in the environment, in household dust, and in humans. Breast
      feeding is a prominent route of exposure in infancy. PBDEs adversely affect
      neurodevelopment in animals. Here, we estimate associations between PBDEs in
      breast milk and behaviour and cognitive skills in children at 36 months of age.
      METHODS: We prospectively studied 304 mothers and their children. We measured
      PBDEs in breast milk collected at 3 months postpartum. At 36 months, we measured
      child behaviour with the parent-rated Behavioral Assessment System for Children 2
      (n = 192), and cognitive skills with the Mullen Scales of Early Learning (n =
      184). We analysed data with robust regression. RESULTS: We detected BDE-28, -47, 
      99, -100, and -153 in >70% of milk samples. For each congener, the highest
      quartile of breast milk PBDE concentration, vs. the lowest, was associated with
      more anxious behaviour, after confounder adjustment. Select congeners were
      associated with increased withdrawal (BDE-28) and improved activity of daily
      living skills (BDE-153). Cognitive skills tended to be positively associated with
      PBDEs, especially language and fine motor skills. However, most estimates were
      imprecise. CONCLUSIONS: Here, lactational PBDE exposure was modestly and
      imprecisely associated with anxiety and withdrawal, but was also associated with
      improved adaptive and cognitive skills. Positive factors associated with breast
      feeding may have mitigated some of the hypothesised adverse neurodevelopmental
      outcomes associated with PBDEs. Further research is needed to inform our
      understanding of PBDE neurotoxicity and how sources of exposure might confound
      neurodevelopmental studies.

PMID- 24313668
TI  - Variation by diagnostic subtype in risk for autism spectrum disorders associated
      with maternal parity among Finnish births.
AB  - BACKGROUND: Associations between maternal parity and outcomes in offspring may
      provide evidence for involvement of prenatal exposures. The objective of this
      study was to determine whether risk for autism spectrum disorders (ASD) is
      associated with maternal parity. METHODS: Diagnoses of childhood autism, Asperger
      syndrome, and pervasive developmental disorder, not otherwise specified (PDD-NOS)
      were examined separately and as a group. The study was conducted in the Finnish
      Prenatal Study of Autism, which is based in a national birth cohort. Children
      born in Finland in 1987-2005 and diagnosed with ASD by 2007 were identified
      through the Finnish Hospital Discharge Register. Four matched controls were
      selected for each case using the Finnish Medical Birth Register. The association
      between parity and each ASD was determined using conditional logistic regression
      and adjusted for number of children in the sibship and other potential
      confounders. RESULTS: ASDs combined showed a pattern of decreasing risk with
      increasing parity (odds ratio OR for fourth or greater vs. first-born children,
      0.43 [95% confidence interval (CI): 0.35, 0.51]). For childhood autism, an
      adjusted OR of 1.51 [95% CI 1.27, 1.81] was observed for second vs. first-born
      children. Associations for Asperger syndrome and PDD-NOS were consistent with
      those for all ASDs. CONCLUSIONS: Differences in patterns of association between
      maternal parity and ASD subtypes may indicate varying contributions of specific
      environmental factors to risk; however, differences in diagnosis or in treatment
      seeking for childhood behavioural problems cannot be ruled out, particularly for
      higher functioning cases.

PMID- 24313669
TI  - Self-reported maternal cigarette smoke exposure during the periconceptional
      period and the risk for omphalocoele.
AB  - BACKGROUND: We investigated whether maternal exposure to cigarette smoke was
      associated with omphalocoele and whether periconceptional folic acid modified the
      association. METHODS:  : We analysed data from the National Birth Defects
      Prevention Study on omphalocoele case (n = 301) and control (n = 8135) mothers
      for infants born from 1997 through 2007. Mothers who reported active smoking or
      exposure to second-hand smoke during the periconceptional period (1 month before
      conception to 3 months after) were considered exposed. Those who reported use of
      folic acid supplements during the same period were considered supplement users.
      Odds ratios and 95% confidence intervals were estimated using multivariable
      logistic regression adjusted for alcohol use, preconception body mass index, and
      race/ethnicity. RESULTS: One hundred fifteen (38.2%) case and 2592 (31.9%)
      control mothers reported exposure to cigarette smoke during the periconceptional
      period. Adjusted odds ratios [95% confidence intervals] were 1.19 [0.94, 1.53]
      for any smoke exposure, 0.87 [0.54, 1.40] for active smoking, 1.38 [1.00, 1.90]
      for second-hand smoke exposure, and 1.16 [0.80, 1.67] for both exposures
      combined. No dose-response relationship was observed. Folic acid-containing
      supplements did not reduce the risk for omphalocoele among women with active or
      second-hand smoke exposure. CONCLUSIONS: Self-reported active maternal smoking,
      with or without exposure to second-hand smoke, during the periconceptional period
      was not associated with omphalocoele. In contrast, there was a possible
      association with periconceptional exposure to second-hand smoke.

PMID- 24313672
TI  - Facile fabrication of PEDOT:PSS/polythiophenes bilayered nanofilms on pure
      organic electrodes and their thermoelectric performance.
AB  - A pure organic PEDOT:PSS nanofilm was used as a working electrode for the first
      time to electrodeposit polymer films of polythiophene (PTh) and its derivatives
      in a boron trifluoride diethyl ether (BFEE) solution, fabricating a novel
      generation of bilayered nanofilms. Cyclic voltammetry (CV) demonstrated good
      electrochemical stability of the as-formed films. Structures and surface
      morphologies were systematically investigated by the characterizations of cross
      section SEM, FT-IR, UV-vis, SEM, and AFM. The resulting films revealed stable and
      enhanced thermoelectric (TE) performances. The electrical conductivity values of
      PEDOT:PSS/PTh, PEDOT:PSS/P3MeT, and PEDOT:PSS/P3HT nanofilms were determined to
      be 123.9, 136.5, and 200.5 S cm(-1), respectively. The power factor reached up to
      be a maximum value of 5.79 MUW m(-1) k(-2). Thus, this technique offers a facile
      approach to a class of bilayered nanofilms, and it may provide a general strategy
      for fabricating a new generation of conducting polymers for more practical
      applications. 

PMID- 24313671
TI  - Stereoselective anticonvulsant and pharmacokinetic analysis of valnoctamide, a
      CNS-active derivative of valproic acid with low teratogenic potential.
AB  - OBJECTIVE: Valnoctamide (VCD), a central nervous system (CNS)-active chiral
      constitutional isomer of valpromide, the corresponding amide of valproic acid
      (VPA), is currently undergoing phase IIb clinical trials in acute mania. VCD
      exhibits stereoselective pharmacokinetics (PK) in animals and humans. The current
      study comparatively evaluated the pharmacodynamics (PD; anticonvulsant activity
      and teratogenicity) and PK of the four individual stereoisomers of VCD. METHODS:
      The anticonvulsant activity of VCD individual stereoisomers was evaluated in
      several rodent anticonvulsant models including maximal electroshock, 6 Hz
      psychomotor, subcutaneous metrazol, and the pilocarpine-induced and soman-induced
      status epilepticus (SE). The PK-PD (anticonvulsant activity) relationship of VCD
      stereoisomers was evaluated following intraperitoneal administration (70 mg/kg)
      to rats. Induction of neural tube defects (NTDs) by VCD stereoisomers was
      evaluated in a mouse strain that was highly susceptible to teratogen-induced
      NTDs. RESULTS: VCD had a stereoselective PK, with (2S,3S)-VCD exhibiting the
      lowest clearance, and consequently a twice-higher plasma exposure than all other
      stereoisomers. Nervertheless, there was less stereoselectivity in VCD
      anticonvulsant activity and each stereoisomer had similar median effective dose
      (ED)50 values in most models. VCD stereoisomers (258 or 389 mg/kg) did not cause
      NTDs. These doses are 3-12 times higher than VCD anticonvulsant ED50 values.
      SIGNIFICANCE: VCD displayed stereoselective PK that did not lead to significant
      stereoselective activity in various anticonvulsant rodent models. If VCD exerted
      its broad-spectrum anticonvulsant activity using a single mechanism of action
      (MOA), it is likely that it would exhibit a stereoselective PD. The fact that
      there was no significant difference between racemic VCD and its individual
      stereoisomers suggests that VCD's anticonvulsant activity is due to multiple
      MOAs.

PMID- 24313674
TI  - Dorsal spinal arachnoid web diagnosed with the quantitative measurement of
      cerebrospinal fluid flow on magnetic resonance imaging.
AB  - An arachnoid web is an abnormal formation of the arachnoid membrane in the spinal
      subarachnoid space that blocks CSF flow and causes syringomyelia. Although the
      precise mechanism of syrinx formation is unknown, dissection of the arachnoid web
      shrinks the syrinx and improves symptoms. Precisely determining the location of
      the arachnoid web is difficult preoperatively, however, because the fine
      structure generally cannot be visualized in usual MRI sequences. In this report
      the authors describe 2 cases of arachnoid web in which the web was preoperatively
      identified using quantitative CSF flow analysis of MRI. By analyzing cardiac
      gated phase-contrast cine-mode MRI in multiple axial planes, the authors
      precisely localized the obstruction of CSF flow on the dorsal side of the spinal
      cord in both patients. This technique also revealed a 1-way valve-like function
      of the arachnoid webs. Imaging led to the early diagnosis of myelopathy related
      to the derangement of CSF flow and allowed the authors to successfully excise the
      webs through limited surgical exposure. 

PMID- 24313673
TI  - Is the signal from the mesophyll to the guard cells a vapour-phase ion?
AB  - Previous studies have suggested that the red light and CO2 responses of stomata
      are caused by a signal from the mesophyll to the guard cells. Experiments were
      conducted to test the idea that this signal is a vapour-phase ion. Stomata in
      isolated epidermes of Tradescantia pallida were found to respond to air ions
      created by an electrode that was positioned under the epidermes. Anthocyanins in
      the epidermes of this species were observed to change colour in response to these
      air ions, and this change in colour was attributed to changes in pH. A similar
      change in lower epidermal colour was observed in intact leaves upon illumination
      and with changes in CO2 concentration. Based on the change in epidermal colour,
      the pH of the epidermis was estimated to be approximately 7.0 in darkness and 6.5
      in the light. Stomata in isolated epidermes responded to pH when suspended over
      (but not in contact with) solutions of different pH. We speculate that stomatal
      responses to CO2 and light are caused by vapour-phase ions, possibly hydronium
      ions that change the pH of the epidermis. 

PMID- 24313675
TI  - Estimation of odontoid process posterior inclination, odontoid height, and pB-C2
      line in the adult population.
AB  - OBJECT: Posterior odontoid process inclination has been associated with Chiari
      malformation Type I in the pediatric population. There are varying reports to
      support a reliable range of odontoid inclination angles in control adults. The
      purpose of this study is to estimate the normal measurements in adults for
      odontoid retroflexion, retroversion, height, and the pB-C2 line (a line drawn
      through the odontoid tip from the ventral dura perpendicular to a second line
      from drawn the basion to the inferoposterior aspect of C-2 vertebral body) to
      establish a normative reference in this population. METHODS: After obtaining
      institutional review board approval, the authors performed a retrospective
      analysis of non-contrast enhanced cervical spine CT scans obtained in 150
      consecutive control adults. Three neuroradiologists measured odontoid
      retroflexion, odontoid retroversion, odontoid height, and the pB-C2 line. The
      cohort was divided into sex and two age groups. Comparisons of the means with
      unpaired 2-tailed t-test were performed. RESULTS: A total of 125 subjects met the
      inclusion criteria; 80 were men and 45 were women (mean age 52 years, range 18-89
      years). The odontoid retroflexion angle ranged from 70 degrees  to 89 degrees 
      (mean 79.3 degrees  +/- 4.9 degrees ), and the odontoid retroversion angle ranged
      from 57 degrees  to 87 degrees  (mean 71.9 degrees  +/- 5.3 degrees ). The range
      and mean of odontoid height were 17-27 mm and 22 +/- 1.8 mm, respectively. The
      mean pB-C2 line was 6.5 +/- 2.1 mm with a range of 0-11.2 mm. The results were
      also compared with previously published pediatric data. CONCLUSIONS: The current
      study demonstrates that the odontoid process in adults is anatomically different
      from that in children: it is longer, more posteriorly inclined, and has a greater
      pB-C2 line. Therefore, utilization of these parameters with previously published
      cutoffs in the pediatric population is not appropriate for surgical planning in
      adults.

PMID- 24313676
TI  - Perfusion imaging of spinal cord contusion: injury-induced blockade and partial
      reversal by beta2-agonist treatment in rats.
AB  - OBJECT: Traumatic injury to the spinal cord results in considerable delayed
      tissue loss. The authors investigated the extent to which ischemia occurs
      following contusion-induced spinal cord injury and whether ischemia exacerbates
      tissue damage that leads to the loss of locomotor function. They also determined
      if ischemia is reversed with beta2-adrenoceptor agonist treatment, which has been
      established to be neuroprotective following contusion injury. METHODS: The extent
      and role of circulation loss in spinal cord injury was determined in an
      established experimental model of contusion injury. The spinal cord dura mater of
      Wistar rats was exposed by performing a laminectomy at T-8 to T-11. Laser Doppler
      perfusion imaging was then used to measure microcirculation in the exposed spinal
      cord. After imaging, a moderately severe contusion injury was produced using a
      weight-drop device unto the exposed dura at T-10. Perfusion imaging was again
      performed, scans were quantitated, and integrated intensities were compared.
      RESULTS: Postinjury imaging revealed an 18%-27% reduction in perfusion in regions
      rostral and caudal to the injury site, and a 68% reduction was observed at the
      contusion epicenter. These perfusion losses persisted for at least 48 hours. At
      24 hours after injury, some rats were intraperitoneally injected with 2 mg/kg of
      the beta2-adrenoceptor agonist clenbuterol, which has been shown to promote the
      partial recovery of locomotor function and spare spinal cord tissue when
      administered within 2 days after contusion injury. Clenbuterol injection caused a
      gradual increase in perfusion, which was detectable at 30 minutes postinjection
      and continued over time, resulting in an 127% overall increase in perfusion at
      the epicenter 24 hours after treatment. CONCLUSIONS: These results suggest that
      the occurrence of chronic perfusion loss after contusion contributes to delayed
      damage and tissue loss. In contrast, beta2-adrenoceptor agonist treatment may
      exert neuroprotection by restoring perfusion, thereby preventing ischemic
      neurodegeneration. The ability of laser Doppler imaging to measure the loss of
      perfusion and its restoration upon treatment suggests that it may have clinical
      utility in the assessment and treatment of spinal cord injury.

PMID- 24313677
TI  - A novel method of anterior lumbosacral cage reconstruction.
AB  - Reconstruction of the lumbosacral junction is a considerable challenge for spinal
      surgeons due to the unique anatomical constraints of this region as well as the
      vectors of force that are applied focally in this area. The standard cages, both
      expandable and nonexpendable, often fail to reconstitute the appropriate
      anatomical alignment of the lumbosacral junction. This inadequate reconstruction
      may predispose the patient to continued back pain and neurological symptoms as
      well as possible pseudarthrosis and instrumentation failure. The authors describe
      their preoperative planning and the technical characteristics of their novel
      reconstruction technique at the lumbosacral junction using a cage with adjustable
      caps. Based precisely on preoperative measurements that maintain the appropriate
      Cobb angle, they performed reconstruction of the lumbosacral junction in a series
      of 3 patients. All 3 patients had excellent installation of the cages used for
      reconstruction. Postoperative CT scans were used to radiographically confirm the
      appropriate reconstruction of the lumbosacral junction. All patients had a
      significant reduction in pain, had neurological improvement, and experienced no
      instrumentation failure at the time of latest follow-up. Taking into account the
      inherent morphology of the lumbosacral junction and carefully planning the
      technical characteristics of the cage installation preoperatively and
      intraoperatively, the authors achieved favorable clinical and radiographic
      outcomes in all 3 cases. Based on this small case series, this technique for
      reconstruction of the lumbosacral junction appears to be a safe and appropriate
      method of reconstruction of the anterior spinal column in this technically
      challenging region of the spine. 

PMID- 24313678
TI  - Determining bruise etiology in muscle tissue using finite element analysis.
AB  - Bruising, the result of capillary failure, is a common physical exam finding due
      to blunt trauma and, depending on location and severity, a potential indicator of
      abuse. Despite its clinical relevance, few studies have investigated the etiology
      of capillary failure. The goal of this study was to determine whether capillaries
      primarily fail under shear stress or hydraulic-induced tensile stress. An
      arteriole bifurcating into four capillaries was modeled using ANSYS 14.0 ((r)) .
      The capillaries were embedded in muscle tissue and a pressure of 20.4 kPa was
      applied. Any tensile stress exceeding 8.4 * 10(4)  Pa was considered failure.
      Results showed that failure occurred directly under the impact zone and where
      capillaries bifurcated, rather than along the line of greatest shear stress,
      indicating that internal tensile stress is likely the primary mode of capillary
      failure in bruising. These results are supported by the concept that bruising can
      occur via blunt trauma in which no shearing lacerations occur. 

PMID- 24313679
TI  - Short co-incubation of gametes combined with early rescue ICSI: an optimal
      strategy for complete fertilization failure after IVF.
AB  - Failed fertilization after conventional IVF is one of the most frustrating
      experiences in assisted reproductive technology. "Late" rescue ICSI may be not an
      optimal strategy for treating unfertilized oocytes. Short co-incubation of
      gametes combined with early rescue ICSI has some advantages for complete
      fertilization failure after IVF. We evaluate the strategy and the optimal time
      for early rescue ICSI. A total of 180 patients underwent short co-incubation of
      gametes combined with early rescue ICSI treatment for complete fertilization
      failure after IVF (study group). A total of 494 ICSI patients with male factor
      infertility served as a control group. Clinical pregnancy rate, implantation
      rate, and live birth rate in the two groups were compared. The study group was
      divided into three different rescue time intervals (<6 h, 6-8 h, and >8 h).
      Clinical pregnancy rate, implantation rate, and live birth rate were comparable
      between the study group and the control group. There was a negative correlation
      between clinical outcomes and rescue time interval.

PMID- 24313681
TI  - Current status of robotic liver resection: a systematic review.
AB  - Robotic surgery is an emerging technique for the management of patients with
      liver disease, and only a limited number of reports are available. A systematic
      search of electronic databases (PubMed, Embase and Cochrane), including only case
      series with more than five patients, identified nine series (with one from our
      institution), which totaled to 232 patients. Overall, the peri-operative outcomes
      of the reported patients are similar to those utilizing the laparoscopic and open
      approaches. Robotic surgery appears to be a valid option for selected hepatic
      resections in experienced hands. It could represent a bridge toward minimally
      invasive approaches for confirmed liver surgeons. By contrast, the long-term
      oncological outcomes remain uncertain and need further studies. 

PMID- 24313680
TI  - Re-evaluation of connexins associated with motoneurons in rodent spinal cord,
      sexually dimorphic motor nuclei and trigeminal motor nucleus.
AB  - Electrical synapses formed by neuronal gap junctions composed of connexin36
      (Cx36) are a common feature in mammalian brain circuitry, but less is known about
      their deployment in spinal cord. It has been reported based on connexin mRNA
      and/or protein detection that developing and/or mature motoneurons express a
      variety of connexins, including Cx26, Cx32, Cx36 and Cx43 in trigeminal
      motoneurons, Cx36, Cx37, Cx40, Cx43 and Cx45 in spinal motoneurons, and Cx32 in
      sexually dimorphic motoneurons. We re-examined the localization of these
      connexins during postnatal development and in adult rat and mouse using
      immunofluorescence labeling for each connexin. We found Cx26 in association only
      with leptomeninges in the trigeminal motor nucleus (Mo5), Cx32 only with
      oligodendrocytes and myelinated fibers among motoneurons in this nucleus and in
      the spinal cord, and Cx37, Cx40 and Cx45 only with blood vessels in the ventral
      horn of spinal cord, including those among motoneurons. By freeze-fracture
      replica immunolabeling, > 100 astrocyte gap junctions but no neuronal gap
      junctions were found based on immunogold labeling for Cx43, whereas 16 neuronal
      gap junctions at postnatal day (P)4, P7 and P18 were detected based on Cx36
      labeling. Punctate labeling for Cx36 was localized to the somatic and dendritic
      surfaces of peripherin-positive motoneurons in the Mo5, motoneurons throughout
      the spinal cord, and sexually dimorphic motoneurons at lower lumbar levels. In
      studies of electrical synapses and electrical transmission between developing and
      between adult motoneurons, our results serve to focus attention on mediation of
      this transmission by gap junctions composed of Cx36.

PMID- 24313682
TI  - Polychlorinated biphenyls in residential dust: sources of variability.
AB  - We characterized the variability in concentrations of polychlorinated biphenyls
      (PCBs) measured in residential dust. Vacuum cleaner samples were collected from
      289 homes in the California Childhood Leukemia Study during two sampling rounds
      from 2001 to 2010 and 15 PCBs were measured by high resolution gas chromatography
      mass spectrometry. Median concentrations of the most abundant PCBs (i.e., PCBs
      28, 52, 101, 105, 118, 138, 153, and 180) ranged from 1.0-5.8 ng per g of dust in
      the first sampling round and from 0.8-3.4 ng/g in the second sampling round. For
      each of these eight PCBs, we used a random-effects model to apportion total
      variation into regional variability (6-11%), intraregional between-home
      variability (27-56%), within-home variability over time (18-52%), and within
      sample variability (9-16%). In mixed-effects models, differences in PCB
      concentrations between homes were explained by home age, with older homes having
      higher PCB levels. Differences in PCB concentrations within homes were explained
      by decreasing time trends. Estimated half-lives ranged from 5-18 years,
      indicating that PCBs are removed very slowly from the indoor environment. Our
      findings suggest that it may be feasible to use residential dust for
      retrospective assessment of PCB exposures in studies of children's health. 

PMID- 24313683
TI  - Comparison of the effects of silver phosphate and selenium nanoparticles on
      Staphylococcus aureus growth reveals potential for selenium particles to prevent
      infection.
AB  - Interactions of silver phosphate nanoparticles (SPNPs) and selenium nanoparticles
      (SeNPs) with Staphylococcus aureus cultures have been studied at the cellular,
      molecular and protein level. Significant antibacterial effects of both SPNPs and
      SeNPs on S. aureus were observed. At a concentration of 300 MUM, SPNPs caused
      37.5% inhibition of bacterial growth and SeNPs totally inhibited bacterial
      growth. As these effects might have been performed due to the interactions of
      nanoparticles with DNA and proteins, the interaction of SPNPs or SeNPs with the
      amplified zntR gene was studied. The presence of nanoparticles decreased the
      melting temperatures of the nanoparticle complexes with the zntR gene by 23% for
      SeNPs and by 12% for SPNPs in comparison with the control value. The
      concentration of bacterial metallothionein was 87% lower in bacteria after
      application of SPNPs (6.3 MUg mg(-1) protein) but was increased by 29% after
      addition of SeNPs (63 MUg mg(-1) protein) compared with the S. aureus control (49
      MUg mg(-1) protein). Significant antimicrobial effects of the nanoparticles on
      bacterial growth and DNA integrity provide a promising approach to reducing the
      risk of bacterial infections that cannot be controlled by the usual antibiotic
      treatments. 

PMID- 24313684
TI  - The structure and dynamics of molecular excitons.
AB  - The photophysical behavior of organic semiconductors is governed by their
      excitonic states. In this review, I classify the three different exciton types
      (Frenkel singlet, Frenkel triplet, and charge transfer) typically encountered in
      organic semiconductors. Experimental challenges that arise in the study of solid
      state organic systems are discussed. The steady-state spectroscopy of
      intermolecular delocalized Frenkel excitons is described, using crystalline
      tetracene as an example. I consider the problem of a localized exciton diffusing
      in a disordered matrix in detail, and experimental results on conjugated polymers
      and model systems suggest that energetic disorder leads to subdiffusive motion.
      Multiexciton processes such as singlet fission and triplet fusion are described,
      emphasizing the role of spin state coherence and magnetic fields in studying
      singlet <-> triplet pair interconversion. Singlet fission provides an example of
      how all three types of excitons (triplet, singlet, and charge transfer) may
      interact to produce useful phenomena for applications such as solar energy
      conversion. 

PMID- 24313685
TI  - Level of acceptance of solid organ xenotransplantation among personnel in
      Spanish, Mexican, and Cuban hospitals.
AB  - BACKGROUND: Xenotransplantation is still a long way from becoming a clinical
      reality. However, in an emergency situation, it could be used as a bridge for
      replacing vital organs until the arrival of a human organ. To analyze the
      attitude toward xenotransplantation among hospital personnel from several
      hospitals in Spain and Latin America. METHODS: A random sample stratified
      according to the type of hospital and job category (n = 2618) in 10 hospitals in
      three different countries: Spain (n = 821), Mexico (n = 1595), and Cuba (n =
      202). A validated questionnaire (PCID-XenoTx Rios) was self-administered and
      completed anonymously by the respondents. RESULTS: If the results of
      xenotransplantation were similar to those achieved using human donor organs, 61%
      (n = 1591) of the respondents would be in favor, while 9% (n = 234) would be
      against and 30% (n = 793) would be unsure. The analysis of the variables
      affecting attitude toward xenotransplantation revealed that attitude varied
      according to the country of reference and was more favorable among personnel in
      Cuban hospitals (70% a favor) than in Spanish (57%) and Mexican ones (62%; P =
      0.000). However, these differences are mainly determined by job category with the
      physicians having the most favorable attitude. The ancillary staff, in contrast,
      had the least favorable attitude (76 vs. 51% respectively; P = 0.000). Of the
      remaining variables, attitude is significantly related to variables connected to
      human donation: attitude toward the different kinds of human organ donation
      (deceased [P < 0.001] and living [P < 0.001]), the possibility of needing a
      transplant oneself in the future (P < 0.001), and attitude toward donating the
      organs of a deceased family member (P = 0.004). CONCLUSIONS: A third of
      healthcare personnel from several hospitals are not in favor of
      xenotransplantation. It is necessary to provide more information about the
      matter, especially in hospitals where there is a preclinical xenotransplantation
      program or where there is access to one, such as in the hospitals in this study.

PMID- 24313686
TI  - Randomized trial of three phototherapy methods for the treatment of acne vulgaris
      in Chinese patients.
AB  - BACKGROUND AND AIMS: Acne vulgaris is common in Asian populations. We compared
      three methods of phototherapy for the treatment of moderate to severe facial acne
      vulgaris in Chinese patients. METHODS: Patients were randomly assigned to receive
      photodynamic therapy (PDT), intense pulsed light (IPL) or blue-red light-emitting
      diode (LED) phototherapy to the right side of the face until the inflammatory
      lesion count reduced by >= 90%. Patients were examined at 1 and 3 months after
      the final treatment. RESULTS: We enrolled 150 patients (92 males; mean age, 28
      years). At 1 month, >=90% clearance or moderate improvement occurred in 46/50
      (92%), 29/50 (58%) and 22/50 (44%) patients in the PDT, IPL and LED groups,
      respectively (mean number of sessions required, PDT: 3 +/- 1.52; IPL: 6 +/- 2.15;
      LED: 9 +/- 3.34). Forty-six (92%) patients experienced mild to moderate pain,
      erythema and edema after PDT, which resolved within 5-7 days. Slight erythema and
      stinging were reported immediately after IPL and LED, resolving within 2 h. After
      3 months, minimal papules and pustules were observed in 4 patients in the PDT
      group, 7 in the IPL group and 12 in the LED group, but no nodular pustules
      recurred. CONCLUSIONS: Phototherapy is efficacious for moderate to severe facial
      acne vulgaris.

PMID- 24313687
TI  - High level of intracellular sperm oxidative stress negatively influences embryo
      pronuclear formation after intracytoplasmic sperm injection treatment.
AB  - This study evaluates the relationship between sperm intracellular reactive oxygen
      species (ROS; H2 O2 , O2 ), DNA fragmentation (DF), low mitochondria membrane
      potential (MMP) of sperm and normal pronuclear formation among intracytoplasmic
      sperm injection (ICSI) patients. Semen samples were obtained from 62 infertile
      male who were candidates for ICSI treatment. After sperm processing, metaphase II
      (MII) oocytes were injected, and the mean percentages of intracellular ROS, MMP
      and DF were evaluated using flow cytometry. The mean percentages of pronuclear
      formation and zygote score (Z) were also recorded, and Pearson, Spearman's rank
      correlation coefficient and Kruskal-Wallis tests were applied to analyse the
      data. The amounts of sperm intracellular H2 O2 and O2- had significant positive
      correlation with low MMP (P < 0.01). The intracellular ROS had a negative
      correlation with pronuclear formation (P < 0.05), and its effect was higher than
      66.66%. In addition, the mean percentages of neither H2 O2 nor O2- affected the
      quality of pronuclear embryos (Z-score). This study shows that although high
      levels of both sperm intracellular H2 O2 and O2- in ICSI patients have
      deleterious effect on sperm MMP, only H2 O2 may interfere in pronuclear
      formation. 

PMID- 24313688
TI  - Structure and properties of the nonface-spiral fullerenes T-C380, D3-C384, D3
      C440, and D3-C672 and their halma and leapfrog transforms.
AB  - The structure and properties of the three smallest nonface-spiral (NS) fullerenes
      NS-T-C380, NS-D3-C384, NS-D3-C440, and the first isolated pentagon NS-fullerene,
      NS-D3-C672, are investigated in detail. They are constructed by either a
      generalized face-spiral algorithm or by vertex insertions followed by a force
      field optimization using the recently introduced program Fullerene. The obtained
      structures were then further optimized at the density functional level of theory
      and their stability analyzed with reference to Ih-C60. The large number of
      hexagons results in a higher stability of the NS-fullerenes compared to C60, but,
      as expected, in a lower stability than most stable isomers. None of the many
      investigated halma transforms on nonspiral fullerenes, NS-T-C380, NS-D3-C384, NS
      D3-C440, and NS-D3-C672, admit any spirals, and we conjecture that all halma
      transforms of NS-fullerenes belong to the class of NS-fullerenes. A similar
      result was found to not hold for the related leapfrog transformation. We also
      show that the first known NS-fullerene with isolated pentagons, NS-D3-C672, is a
      halma transform of D3-C168.

PMID- 24313689
TI  - Design of a metal-organic framework with enhanced back bonding for separation of
      N2 and CH4.
AB  - Gas separations with porous materials are economically important and provide a
      unique challenge to fundamental materials design, as adsorbent properties can be
      altered to achieve selective gas adsorption. Metal-organic frameworks represent a
      rapidly expanding new class of porous adsorbents with a large range of
      possibilities for designing materials with desired functionalities. Given the
      large number of possible framework structures, quantum mechanical computations
      can provide useful guidance in prioritizing the synthesis of the most useful
      materials for a given application. Here, we show that such calculations can
      predict a new metal-organic framework of potential utility for separation of
      dinitrogen from methane, a particularly challenging separation of critical value
      for utilizing natural gas. An open V(II) site incorporated into a metal-organic
      framework can provide a material with a considerably higher enthalpy of
      adsorption for dinitrogen than for methane, based on strong selective back
      bonding with the former but not the latter. 

PMID- 24313690
TI  - 5-lipoxygenase: a promising drug target against inflammatory diseases-biochemical
      and pharmacological regulation.
AB  - 5-Lipoxygenase (5-LO) is the key enzyme involved in the synthesis of pro
      inflammatory leukotrienes (LTs) and has become a prime target for new drug
      discovery research and development efforts by the pharmaceutical and biotech
      industry. The pathophysiological effects of LTs can be modulated by the selective
      inhibition of 5-LO. In this review, we summarize the established dogma and recent
      progress on the biochemical and pharmacological regulation of 5-LO and its
      diverse cellular partners. In the last decade, significant research efforts have
      led to the exploitation of 5-LO pathway for developing new drugs against
      inflammatory diseases. Despite few setbacks, a number of promising molecules have
      moved into clinical development. These fundamental discoveries and proof-of
      concept studies will ultimately be helpful in delineating how 5-LO pathway
      participates in the development of disease phenotype and what are possible key
      biomarkers of disease progression and regression. Elucidation of molecular
      mechanism-of-action of 5-LO in individual cell types will pave the way for
      improving efficacy parameters. Taken together, this combined knowledge about the
      5-LO pathway would be helpful in planning collaborative and targeted R&D efforts,
      by the academic laboratories and pharmaceutical/ biotech industry, for the
      discovery and development of novel, efficacious and safer drugs against multiple
      diseases. 

PMID- 24313691
TI  - Metabolic syndrome: comparison of prevalence in young adults at 3 land-grant
      universities.
AB  - OBJECTIVE: The study examines metabolic syndrome (MetS) among college students at
      3 geographically distinct US campuses. PARTICIPANTS: Undergraduates (N = 360; 68%
      women), 18 to 24 years of age, were recruited at each public university in
      January and February 2011. MetS prevalence was evaluated in 83% (n = 299)
      participants. METHODS: Anthropometric, biochemical, and clinical measures were
      collected in the fasted state. RESULTS: Twelve percent of college men and 6% of
      college women met the clinical definition of MetS. Males were more likely to have
      >= 2 individual MetS criteria than females (33% vs 16%; p < .05). Prevalence and
      individual criteria of MetS differed between the 3 regions. Obese and overweight
      students met significantly more MetS criteria and had higher C-reactive protein
      levels than normal-weight students (both p < .05). CONCLUSION: Findings suggest
      that MetS prevalence among college students differs by sex, weight status, and
      region. Further research is needed to identify effective, targeted interventions
      that are regionally appropriate for this population.

PMID- 24313692
TI  - Understanding tobacco-related attitudes among college and noncollege young adult
      hookah and cigarette users.
AB  - OBJECTIVE: To examine differences in tobacco-related attitudes and hookah and
      cigarette use among college and noncollege young adults. PARTICIPANTS: Time
      location samples of young adult bar patrons in San Diego, California (N = 2,243),
      Tulsa (N = 2,095) and Oklahoma City (N = 2,200), Oklahoma, Albuquerque (N =
      1,044) and Las Cruces (N = 894), New Mexico, between September 2009 and July
      2011. METHODS: Multinomial logistic regression examined associations between
      hookah and cigarette use and tobacco-related attitudes. RESULTS: Current college
      students and graduates are less likely to smoke cigarettes, but more likely to
      use hookah. Among current hookah users, 22.6% were hookah-only users and 77.4%
      were dual users (cigarettes and hookah). College status is associated with
      different hookah use patterns, and those with anti-tobacco industry attitudes
      were more likely to smoke hookah. CONCLUSIONS: Novel interventions are needed for
      college students using hookah. Existing strategies targeting smokers with anti
      tobacco industry messages may be irrelevant to hookah users.

PMID- 24313693
TI  - Feasibility of a prototype web-based acceptance and commitment therapy prevention
      program for college students.
AB  - OBJECTIVE: This study examined the feasibility of a prototype Web-based
      acceptance and commitment therapy (ACT) program for preventing mental health
      problems among college students. PARTICIPANTS: Undergraduate first-year students
      (N = 76) participated between May and November 2011. METHODS: Participants were
      randomized to ACT or a waitlist, with assessments conducted at baseline,
      posttherapy, and 3-week follow-up. Waitlist participants accessed the program
      after the second assessment. RESULTS: Program usability/usage data indicated high
      program acceptability. Significant improvements were found for ACT knowledge,
      education values, and depression with ACT relative to waitlist. Subgroup analyses
      indicated that ACT decreased depression and anxiety relative to waitlist among
      students with at least minimal distress. Within the ACT condition, significant
      improvements were observed from baseline to 3-week follow-up on all outcome and
      process measures. CONCLUSIONS: Results provide preliminary support for the
      feasibility of a Web-based ACT prevention program.

PMID- 24313694
TI  - Evaluation of the acceptability and feasibility of a computer-tailored
      intervention to increase human papillomavirus vaccination among young adult
      women.
AB  - OBJECTIVE: To examine acceptability and feasibility of a Transtheoretical Model
      (TTM)-based computer-tailored intervention (CTI) for increasing human
      papillomavirus (HPV) vaccination in college-aged women. PARTICIPANTS: Two hundred
      forty-three women aged 18-26 were recruited between February and May of 2011.
      METHODS: Participants completed the intervention and a 14-item evaluation of
      intervention content and delivery. RESULTS: Most participants had heard of HPV
      (91%), but the majority (57%) of participants were in Precontemplation for
      getting vaccinated. Eighty-nine percent of participants rated the CTI positively
      across all acceptability items, and 91% endorsed intention to get vaccinated
      after intervention. Although average ratings in each demographic subgroup were
      positive, Hispanic women and participants in more advanced stages of change rated
      the program more favorably than non-Hispanic and earlier-stage participants.
      Additionally, HPV knowledge was higher among white/non-Hispanic participants.
      CONCLUSIONS: Initial acceptability and feasibility data for this intervention are
      promising. Its computer-based, individually tailored format is state of the art
      and ideal for inexpensive dissemination.

PMID- 24313695
TI  - Stress, coping, and internet use of college students.
AB  - College students experience stressful life events and little research exists on
      the role the Internet may play in students' coping. OBJECTIVE: The purpose of the
      present study was to examine associations among perceived stress, time spent on
      the Internet, underlying motives for utilizing the Internet, problematic Internet
      use, and traditional approaches to coping. PARTICIPANTS: Data were collected from
      267 college seniors during March of 2011. METHODS: Participants completed an
      online survey containing measures of coping, motives for utilizing the Internet,
      problematic online behavior, perceived stress, and background information.
      RESULTS: Being female, avoidant-emotional coping, and online motive to cope were
      positively associated with perceived stress and months since most stressful life
      event and online motive to enhance were negatively associated with stress.
      CONCLUSIONS: Professionals working with college students will benefit from using
      a nuanced approach to assessing students' online behavior, including an
      assessment of underlying motives for use.

PMID- 24313696
TI  - Exercise and cardiometabolic risk factors in graduate students: a longitudinal,
      observational study.
AB  - OBJECTIVE: To evaluate cardiometabolic risk of students longitudinally and
      compare them with age-matched national samples. PARTICIPANTS: Participants are
      134 graduate students enrolled between August 2005 and May 2010. METHODS:
      Students were assessed at the beginning and end of their 3-year curriculum.
      Comparative samples included 966 National Health and Nutrition Examination Survey
      participants and 5,154 National College Health Assessment respondents. RESULTS:
      Most students had desirable weight, blood glucose, lipids, and fitness at both
      time points. However, 26.9% had elevated blood pressure, 29.9% performed aerobic
      exercise < 3 days/week, and 80.6% consumed < 5 fruits/vegetables daily. Relative
      to young adults nationwide, these students exhibited more favorable exercise
      patterns, dietary patterns, and cardiometabolic indices. Over time, increases in
      adiposity and decreases in exercise frequency correlated with adverse changes in
      lipid concentrations and fitness. CONCLUSIONS: Small changes in lifestyle
      behaviors and adiposity within a healthy cohort of young adults significantly
      influenced cardiometabolic indices during their graduate career.

PMID- 24313697
TI  - Measuring bystander attitudes and behavior to prevent sexual violence.
AB  - OBJECTIVE: The purpose of this study is to further investigate the factor
      structure and strength of the Bystander Attitude Scale-Revised and Bystander
      Behavior Scale-Revised (BAS-R and BBS-R). PARTICIPANTS: First-year students (N =
      4,054) at a large public university in the Northeast completed a survey in 2010
      as part of a larger longitudinal study of a sexual violence bystander education
      intervention program on campus. METHODS: Exploratory structural equation modeling
      was used to analyze survey responses to the BAS-R and BBS-R. RESULTS: For BAS-R,
      the best fit was a 4-factor model: (1) high-risk situations, (2) postassault
      support for victims, (3) postassault reporting of perpetrators, and (4) proactive
      opportunities. BBS-R was a 2-factor model: (1) intervention opportunities before,
      during, or after an assault, and (2) proactive opportunities. CONCLUSION: The BAS
      R and BBS-R provide reliable tools that can be utilized to evaluate sexual
      violence bystander programs.

PMID- 24313698
TI  - Associations between physical activity and health-related factors in a national
      sample of college students.
AB  - OBJECTIVE: To examine associations between meeting the current moderate to
      vigorous physical activity (MVPA) recommendation and health-related factors in a
      national sample of college students. PARTICIPANTS: Participants (N = 67,861)
      completed the National College Health Assessment II during the Fall 2008/Spring
      2009 academic year. METHODS: Hierarchical binary logistic regression was used to
      examine the contribution of 19 variables in explaining whether or not
      participants met the MVPA recommendation. RESULTS: Meeting the MVPA
      recommendation was associated with several protective factors among college
      students, including adequate daily fruit and vegetable consumption, positive
      perception of general health, healthy body mass index, consistent seatbelt use,
      not smoking cigarettes, less perceived depression, and adequate sleep. In
      addition, meeting the MVPA recommendation was also significantly associated with
      a few risky behaviors including binge drinking, physical fighting, and multiple
      sexual partners. CONCLUSIONS: College student PA interventions should consider
      also addressing fruit/vegetable consumption and binge drinking.

PMID- 24313699
TI  - Mental health and clinical correlates in lesbian, gay, bisexual, and queer young
      adults.
AB  - OBJECTIVE: This study examined the prevalence of mental health disorders and
      their clinical correlates in a university sample of lesbian, gay, bisexual, and
      queer (LGBQ) students. PARTICIPANTS: College students at a large public
      university. METHODS: An anonymous, voluntary survey was distributed via random e
      mail generation to university students during April and May of 2011. LGBQ
      students were compared with their heterosexual counterparts on psychological and
      physical status as well as academic performance. RESULTS: LGBQ students reported
      worse depressive symptoms, higher levels of perceived stress, considered
      themselves less attractive, and were more likely to be overweight. LGBQ students
      were significantly more likely to report histories of affective, substance use,
      and certain anxiety disorders as well as compulsive sexual behavior and
      compulsive buying. CONCLUSIONS: The higher rates of many psychiatric conditions
      among LGBQ students underscore the need for universities to provide LGBQ students
      a nonjudgmental environment to discuss sexual orientation and health issues.

PMID- 24313702
TI  - Trends and synergies in intellectual disability research.

PMID- 24313701
TI  - Do motives matter in male circumcision? 'Conscientious objection' against the
      circumcision of a Muslim child with a blood disorder.
AB  - Whilst there have been serious attempts to locate the practice of male
      circumcision for religious motives in the context of the (respective) religion's
      narrative and community, the debate, when referring to a clinical context, is
      often more nuanced. This article will contribute further to the debate by
      contextualising the Islamic practice of male circumcision within the clinical
      setting typical of a contemporary hospital. It specifically develops an
      additional complication; namely, the child has a pre-existing blood disorder. As
      an approach to contributing to the circumcision debate further, the ethics of a
      conscientious objection for secular motives towards a religiously-motivated
      clinical intervention will be explored. Overall, the discussion will provide
      relevance for such debates within the value-systems of a multi-cultural society.
      This article replicates several approaches to deconstructing a request for
      conscientious refusal of non-therapeutic circumcision by a Clinical Ethics
      Committee (CEC), bringing to light certain contradictions that occur in
      normatively categorizing motives for performing the circumcision. 

PMID- 24313703
TI  - Altered autonomic activity and reactivity in depression revealed by heart-rate
      variability measurement during rest and task conditions.
AB  - AIM: The aim of the present study was to assess autonomic activity and reactivity
      reflecting arousal functions in depression using heart-rate variability (HRV) and
      heart rate (HR) measurements. METHODS: HRV and HR were measured in drug-naive
      depressed (n = 22) and normal subjects (n = 47) both at rest and during task
      execution (random number generation). Rest activity was measured both before and
      after the task. Following power spectrum analysis of the heart rate trend, the
      high-frequency component (HF: 0.15-0.4 Hz) and the ratio of the low-frequency
      component (LF: 0.04-0.15 Hz) to the HF (LF/HF) were used as the parameters
      corresponding to parasympathetic and sympathetic activities, respectively.
      RESULTS: For the depressed subjects, HF was lower during the initial rest
      condition, was less inhibitedduring the task condition, and exceeded the initial
      rest level during the rest condition following the task. LF/HF was higher at
      rest, increased less during the task, and maintained its higher level during the
      rest condition after the task. HR was higher during the initial rest period and
      responded less to the task. CONCLUSION: The results indicate alteration not only
      of baseline activity but also of reactivity to behavioral changes in depression.
      These altered autonomic measures are possibly related to the disturbed arousal
      function and can be used as diagnostic measures and in clinical evaluation.

PMID- 24313704
TI  - Recovery of upper limb muscle function in chronic fatigue syndrome with and
      without fibromyalgia.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) patients frequently complain of muscle
      fatigue and abnormally slow recovery, especially of the upper limb muscles during
      and after activities of daily living. Furthermore, disease heterogeneity has not
      yet been studied in relation to recovery of muscle function in CFS. Here, we
      examine recovery of upper limb muscle function from a fatiguing exercise in CFS
      patients with (CFS+FM) and without (CFS-only) comorbid fibromyalgia and compare
      their results with a matched inactive control group. DESIGN: In this case-control
      study, 18 CFS-only patients, 30 CFS+FM patients and 30 healthy inactive controls
      performed a fatiguing upper limb exercise test with subsequent recovery measures.
      RESULTS: There was no significant difference among the three groups for maximal
      handgrip strength of the non-dominant hand. A significant worse recovery of upper
      limb muscle function was found in the CFS+FM, but not in de CFS-only group
      compared with the controls (P < 0.05). CONCLUSIONS: This study reveals, for the
      first time, delayed recovery of upper limb muscle function in CFS+FM, but not in
      CFS-only patients. The results underline that CFS is a heterogeneous disorder
      suggesting that reducing the heterogeneity of the disorder in future research is
      important to make progress towards a better understanding and uncovering of
      mechanisms regarding the nature of divers impairments in these patients.

PMID- 24313706
TI  - Infrared spectroscopy of nicotinamide adenine dinucleotides in one and two
      dimensions.
AB  - The development of multidimensional spectroscopic tools capable of resolving site
      specific information about proteins and enzymes in the solution phase is an
      important aid to our understanding of biomolecular mechanisms, structure, and
      dynamics. Nicotinamide adenine dinucleotide (NAD) is a common biological
      substrate and so offers significant potential as an intrinsic vibrational probe
      of protein-ligand interactions but its complex molecular structure and
      incompletely characterized infrared spectrum currently limit its usefulness.
      Here, we report the FTIR spectroscopy of the oxidized and reduced forms of NAD at
      a range of pD values that relate to the "folded" and "unfolded" forms of the
      molecules that exist in solution. Comparisons with structural analogs and the use
      of density functional theory simulations provide a full assignment of the
      observed modes and their complex pD dependencies. Finally, ultrafast two
      dimensional infrared spectra of the oxidized and reduced forms of NAD are
      reported and their usefulness as biomolecular probes is discussed. 

PMID- 24313705
TI  - Airway contractility in the precision-cut lung slice after cryopreservation.
AB  - An emerging tool in airway biology is the precision-cut lung slice (PCLS).
      Adoption of the PCLS as a model for assessing airway reactivity has been hampered
      by the limited time window within which tissues remain viable. Here we
      demonstrate that the PCLS can be frozen, stored long-term, and then thawed for
      later experimental use. Compared with the never-frozen murine PCLS, the frozen
      thawed PCLS shows metabolic activity that is decreased to an extent comparable to
      that observed in other cryopreserved tissues but shows no differences in cell
      viability or in airway caliber responses to the contractile agonist methacholine
      or the relaxing agonist chloroquine. These results indicate that freezing and
      long-term storage is a feasible solution to the problem of limited viability of
      the PCLS in culture.

PMID- 24313709
TI  - An evaluation of audiology service improvement documentation in England using the
      chronic care model and content analysis.
AB  - OBJECTIVE: Implementation of the chronic care model (CCM) is associated with
      improved outcomes for patients. It follows that any proposed policy or
      implementation plan that maps highly onto the CCM is more likely to lead to
      improved outcomes. The aim of this study was to compare long-term condition (LTC)
      policy documents and audiology quality standard documents with the CCM and to
      highlight the need for further research in service implementation and clinical
      outcome. DESIGN: We carried out a keyword-in-context content analysis of relevant
      documents. STUDY SAMPLE: Documents relating to health department policy on LTCs,
      audiology service improvement initiatives in England and the CCM. RESULTS: This
      analysis shows that current audiology implementation documents in England map
      poorly onto the CCM compared to health policy documents relating to the
      management of LTCs. The biggest discrepancies occur in self-management support,
      delivery system design, and decision support. These elements are supported by the
      best evidence of potential improvements in clinical outcome. CONCLUSIONS: Our
      content analysis of audiology service quality improvement documents in England
      suggests they compare poorly to some elements of the CCM. We discuss the
      implications this might have for future research.

PMID- 24313707
TI  - Phytochelatin-metal(loid) transport into vacuoles shows different substrate
      preferences in barley and Arabidopsis.
AB  - Cadmium (Cd) and arsenic (As) are toxic to all living organisms, including plants
      and humans. In plants, Cd and As are detoxified by phytochelatins (PCs) and
      metal(loid)-chelating peptides and by sequestering PC-metal(loid) complexes in
      vacuoles. Consistent differences have been observed between As and Cd
      detoxification. Whereas chelation of Cd by PCs is largely sufficient to detoxify
      Cd, As-PC complexes must be sequestered into vacuoles to be fully detoxified. It
      is not clear whether this difference in detoxification pathways is ubiquitous
      among plants or varies across species. Here, we have conducted a PC transport
      study using vacuoles isolated from Arabidopsis and barley. Arabidopsis vacuoles
      accumulated low levels of PC2 -Cd, and vesicles from yeast cells expressing
      either AtABCC1 or AtABCC2 exhibited negligible PC2 -Cd transport activity
      compared with PC2 -As. In contrast, barley vacuoles readily accumulated
      comparable levels of PC2 -Cd and PC2 -As. PC transport in barley vacuoles was
      inhibited by vanadate, but not by ammonium, suggesting the involvement of ABC
      type transporters. Interestingly, barley vacuoles exhibited enhanced PC2
      transport activity when essential metal ions, such as Zn(II), Cu(II) and Mn(II),
      were added to the transport assay, suggesting that PCs might contribute to the
      homeostasis of essential metals and detoxification of non-essential toxic
      metal(loid)s. 

PMID- 24313710
TI  - Influence of g-C3N4 nanosheets on thermal stability and mechanical properties of
      biopolymer electrolyte nanocomposite films: a novel investigation.
AB  - A series of sodium alginate (SA) nanocomposite films with different loading
      levels of graphitic-like carbon nitride (g-C3N4) were fabricated via the casting
      technique. The structure and morphology of nanocomposite films were investigated
      by X-ray powder diffraction, Fourier transform infrared spectroscopy, scanning
      electron microscopy, and transmission electron microscopy. Thermogravimetric
      analysis results suggested that thermal stability of all the nanocomposite films
      was enhanced significantly, including initial thermal degradation temperature
      increased by 29.1  degrees C and half thermal degradation temperature improved by
      118.2  degrees C. Mechanical properties characterized by tensile testing and
      dynamic mechanical analysis measurements were also reinforced remarkably. With
      addition of 6.0 wt % g-C3N4, the tensile strength of SA nanocomposite films was
      dramatically enhanced by 103%, while the Young's modulus remarkably increased
      from 60 to 3540 MPa. Moreover, the storage modulus significantly improved by
      34.5% was observed at loadings as low as 2.0 wt %. These enhancements were
      further investigated by means of differential scanning calorimetry and real time
      Fourier transform infrared spectra. A new perspective of balance was proposed to
      explain the improvement of those properties for the first time. At lower than 1.0
      wt % loading, most of the g-C3N4 nanosheets were discrete in the SA matrix,
      resulting in improved thermal stability and mechanical properties; above 1.0 wt %
      and below 6.0 wt % content, the aggregation was present in SA host coupled with
      insufficient hydrogen bondings limiting the barrier for heat and leading to the
      earlier degradation and poor dispersion; at 6.0 wt % addition, the favorable
      balance was established with enhanced thermal and mechanical performances.
      However, the balance point of 2.0 wt % from dynamic mechanical analysis was due
      to combination of temperature and agglomeration. The work may contribute to a
      potential research approach for other nanocomposites. 

PMID- 24313711
TI  - Phenolphthalein false-positive reactions from legume root nodules.
AB  - Presumptive tests for blood play a critical role in the examination of physical
      evidence and in the determination of subsequent analysis. The catalytic power of
      hemoglobin allows colorimetric reactions employing phenolphthalein (Kastle-Meyer
      test) to indicate "whether" blood is present. Consequently, DNA profiles
      extracted from phenolphthalein-positive stains are presumed to be from blood on
      the evidentiary item and can lead to the identification of "whose" blood is
      present. Crushed nodules from a variety of legumes yielded phenolphthalein false
      positive reactions that were indistinguishable from true bloodstains both in
      color quality and in developmental time frame. Clothing and other materials
      stained by nodules also yielded phenolphthalein false-positive reactivity for
      several years after nodule exposure. Nodules from leguminous plants contain a
      protein (leghemoglobin) which is structurally and functionally similar to
      hemoglobin. Testing of purified leghemoglobin confirmed this protein as a source
      of phenolphthalein reactivity. A scenario is presented showing how the presence
      of leghemoglobin from nodule staining can mislead investigators. 

PMID- 24313712
TI  - Phosphorus speciation and treatment using enhanced phosphorus removal
      bioretention.
AB  - This field research investigated the water quality performance of a traditional
      bioretention cell retrofitted with 5% (by mass) water treatment residual (WTR)
      for enhanced phosphorus removal. Results indicate that WTR incorporation into the
      bioretention media does not negatively influence the infiltration mechanism of
      the bioretention system. Total suspended solids (TSS), total phosphorus (TP), and
      particulate phosphorus (PP) concentrations in runoff inflow were significantly
      reduced compared to outflow due to filtration of particulate matter. TP
      concentrations were significantly reduced by the bioretention cell; before WTR
      retrofit TP export occurred. Although net removal of soluble reactive phosphorus
      (SRP) and dissolved organic phosphorus (DOP) from incoming runoff was not found,
      leaching of dissolved phosphorus (DP) was prevented not only from incoming
      runoff, but also from the media and captured PP. Near constant outflow SRP and
      DOP concentrations suggest an equilibrium adsorption treatment mechanism. Both
      event mean concentrations and mass loads were reduced for TSS and all P species.
      Pollutant mass removals were higher than the event mean concentration removals
      due to the attenuation of volume by the bioretention media. 

PMID- 24313713
TI  - Future directions for clinical toxicology and toxicologists.

PMID- 24313714
TI  - Painful and tender muscles: dry needling can reduce myofascial pain related to
      trigger points muscles.

PMID- 24313715
TI  - Posterior dislocation of the elbow.

PMID- 24313716
TI  - Chronic low back and left lower extremity pain in an elderly woman.

PMID- 24313717
TI  - Expanding the discussion on movement versus pathoanatomic diagnosis.

PMID- 24313720
TI  - Ankle stability and movement coordination impairments: ankle ligament sprains.

PMID- 24313721
TI  - A milestone in xenotransplantation research.

PMID- 24313722
TI  - Application of sunscreen--theory and reality.
AB  - We present research on sunscreen use with possible pitfalls and discuss theory
      vs. reality. A literature review in PubMed was conducted using the terms
      'sunscreen application', 'sunscreen use' and 'sun protection factor'. The sun
      protection factor (SPF) of sunscreens are tested using a thickness of 2 mg/cm(2)
      , but investigations show that sunscreen under natural conditions is applied
      insufficiently with amounts about 0.39 to 1.0 mg/cm(2) , which decreases the
      protection factor considerably. It has been shown that early reapplication or use
      of very high SPF (70-100) may partly compensate for the discrepancy between the
      amounts of sunscreen applied during testing and in reality, and that sunscreen
      application can be improved by education of consumers. Missing areas and
      ultraviolet radiation exposure before sunscreen application are other pitfalls
      that reduce the protective effect of sunscreens considerably. Current sunscreen
      labelling overrates the protective effect of a given sunscreen when the reality
      of sunscreen use is taken into account. This may possibly mislead consumers to
      feel it is safe to extend sun exposure. Alternatively to educating people to use
      large amounts of sunscreen, we suggest a simple teaching strategy: (1) Apply
      before sun exposure and (2) Reapply once within 1 h.

PMID- 24313724
TI  - Giant Zn14 molecular building block in hydrogen-bonded network with permanent
      porosity for gas uptake.
AB  - In situ imidazolate-4,5-diamide-2-olate linker generation leads to the formation
      of a [Zn14(L2)12(O)(OH)2(H2O)4] molecular building block (MBB) with a Zn6
      octahedron inscribed in a Zn8 cube. The MBBs connect by amide-amide hydrogen
      bonds to a 3D robust supramolecular network which can be activated for N2, CO2,
      CH4, and H2 gas sorption. 

PMID- 24313725
TI  - Stable numerosity representations irrespective of magnitude context in macaque
      prefrontal cortex.
AB  - Cognitively demanding tasks require neurons of the prefrontal cortex (PFC) to
      encode divergent behaviorally relevant information. In discrimination tasks with
      arbitrary and learned categories, context-specific parameters shape and adapt the
      tuning functions of PFC neurons. We explored if and how selectivity of PFC
      neurons to visual numerosities, a 'natural' abstract category, may change
      depending on the magnitude context. Two monkeys discriminated visual numerosities
      (varying numbers of dot items) in a delayed match-to-sample (DMS) task while
      single-cell activity was recorded from the lateral PFC. During a given recording
      session, the numerosity task was either presented in isolation or randomly
      intermixed with DMS tasks with line lengths and colors as discriminative stimuli.
      We found that the context of numerosity discriminations did not influence the
      response properties of numerosity detectors. The numerosity tuning curves of
      selective neurons, i.e. the preferred numerosity and the sharpness of tuning,
      remained stable, irrespective of whether the numerosity task was presented in a
      pure numerosity block or a mixed magnitude block. Our data suggest that
      numerosity detectors in the PFC do not adapt their response properties to code
      stimuli according to changing magnitude context. Rather, numerosity
      representations seem to rely on a sparse and stable 'labeled line' code. In
      contrast to arbitrarily learned categories, numerosity as a 'natural' category
      may possess a privileged position and their neuronal representations could thus
      remain unaffected by magnitude context. 

PMID- 24313726
TI  - Controlled release of analgesic drugs from porous bioresorbable structures for
      various biomedical applications.
AB  - Pain is one of the most common patient complaints encountered by health
      professionals and remains the number one cause of absenteeism and disability. In
      the current study, analgesic-eluting bioresorbable porous structures prepared
      using the freeze-drying of inverted emulsions technique were developed and
      studied. These drug-eluting structures can be used for coating fibers or
      implants, or for creating standalone films. They are ideal for forming
      biomedically important structures that can be used for various applications, such
      as wound dressings that provide controlled release of analgesics to the wound
      site in addition to their wound dressing role. Our investigation focused on the
      effects of the inverted emulsion's parameters on the shell microstructure and on
      the resulting drug-release profile of ibuprofen and bupivacaine. The release
      profiles of ibuprofen formulations exhibited a diffusion-controlled pattern,
      ranging from several days to 21 days, whereas bupivacaine formulations exhibited
      an initial burst release followed by a three-phase release pattern over a period
      of several weeks. Higher organic to aqueous phase ratios and higher polymer
      contents reduced the burst release of both drugs and prolonged their release due
      to lower porosity. Overall, the drug-eluting porous structures loaded with either
      ibuprofen or bupivacaine demonstrated a promising potential for use in various
      applications that require pain relief. 

PMID- 24313727
TI  - Impact of using a fast-freezing technique and different thawing protocols on
      viability and fertility of frozen equine spermatozoa.
AB  - The effects of freezing technique and thawing protocol on thawed semen viability
      and fertility were studied. Ejaculates from 5 stallions (n = 25) were frozen by
      conventional or a fast-freezing technique. Frozen semen was thawed by two thawing
      protocols (37  degrees C 30 s(-1) or 75  degrees C 7 s(-1) ). Thawed semen was
      evaluated by progressive motility, vigour, morphology and plasma membrane
      integrity. Mares (n = 25) were inseminated with 300 (n = 11) or 150 (n = 14)
      million spermatozoa. A greater (P < 0.05) vigour and progressively motile
      spermatozoa were detected, respectively, at thawing and after 20 min post-thawing
      in the fast-freezing technique than in the conventional one. Plasma membrane
      integrity was also greater (P < 0.05) in semen frozen with the fast-freezing
      technique. Semen viability was not affected by thawing protocol. Pregnancy rate
      using the fast-freezing technique was 76% (19/25), and did not differ (P > 0.05)
      between insemination doses. We concluded that the 150 million progressively
      motile spermatozoa per dose using a deep-horn insemination maximises the use of
      equine semen. The fast-freezing technique, as compared to the conventional one,
      efficiently preserves the viability and fertilising capacity of spermatozoa,
      indicating a new method to improve the fertility of frozen equine semen. 

PMID- 24313728
TI  - Pilot feasibility study of a brief, tailored mobile health intervention for
      depression among patients with chronic pain.
AB  - This pilot feasibility study investigated a brief, tailored mobile health
      intervention to provide brief treatment and motivate further depression treatment
      seeking among patients with comorbid chronic pain. The computer tablet
      intervention was delivered in a hospital clinic using a blended motivational
      interviewing and cognitive behavioral therapy approach. Individuals were at least
      age 18, and screened positive for depression during a visit for chronic pain.
      Participants completed assessments before the intervention and at two-week follow
      up. The 64 participants were most often over 50 years old, female, and Caucasian.
      Participant ratings demonstrated an increase in interest to seek depression
      treatment and willingness to make life changes to mitigate symptoms. A
      significant reduction in mean depression score and non-significant reductions on
      both measures of disability were observed. This intervention was feasible and
      acceptable, demonstrated promise in reducing depression and increasing treatment
      interest, and should be tested in a trial. 

PMID- 24313729
TI  - Clarifying the role of the mental health peer specialist in Massachusetts, USA:
      insights from peer specialists, supervisors and clients.
AB  - Mental health peer specialists develop peer-to-peer relationships of trust with
      clients to improve their health and well-being, functioning in ways similar to
      community health workers. Although the number of peer specialists in use has been
      increasing, their role in care teams is less defined than that of the community
      health worker. This qualitative study explored how the peer specialist role is
      defined across different stakeholder groups, the expectations for this role and
      how the peer specialist is utilised and integrated across different types of
      mental health services. Data were collected through interviews and focus groups
      conducted in Massachusetts with peer specialists (N = 44), their supervisors (N =
      14) and clients (N = 10) between September 2009 and January 2011. A consensus
      coding approach was used and all data outputs were reviewed by the entire team to
      identify themes. Peer specialists reported that their most important role is to
      develop relationships with clients and that having lived mental health experience
      is a key element in creating that bond. They also indicated that educating staff
      about the recovery model and peer role is another important function. However,
      they often felt a lack of clarity about their role within their organisation and
      care team. Supervisors valued the unique experience that peer specialists bring
      to an organisation. However, without a defined set of expectations for this role,
      they struggled with training, guiding and evaluating their peer specialist staff.
      Clients reported that the shared lived experience is important for the
      relationship and that working with a peer specialist has improved their mental
      health. With increasing support for person-centred integrated healthcare delivery
      models, the demand for mental health peer specialist services will probably
      increase. Therefore, clearer role definition, as well as workforce development
      focused on team orientation, is necessary for peer specialists to be fully
      integrated and supported in care teams.

PMID- 24313723
TI  - Resolution of acute inflammation in the lung.
AB  - Acute inflammation in the lung is essential to health. So too is its resolution.
      In response to invading microbes, noxious stimuli, or tissue injury, an acute
      inflammatory response is mounted to protect the host. To limit inflammation and
      prevent collateral injury of healthy, uninvolved tissue, the lung orchestrates
      the formation of specialized proresolving mediators, specifically lipoxins,
      resolvins, protectins, and maresins. These immunoresolvents are agonists for
      resolution that interact with specific receptors on leukocytes and structural
      cells to blunt further inflammation and promote catabasis. This process appears
      to be defective in several common lung diseases that are characterized by excess
      or chronic inflammation. Here, we review the molecular and cellular effectors of
      resolution of acute inflammation in the lung. 

PMID- 24313730
TI  - Structural investigation of cycloheptathiophene-3-carboxamide derivatives
      targeting influenza virus polymerase assembly.
AB  - The limited number of drug classes licensed for treatment of influenza virus
      (Flu), together with the continuous emergence of viral variants and drug
      resistant mutants, highlights the urgent need to find antivirals with novel
      mechanisms of action. In this context, the viral RNA-dependent RNA polymerase
      (RdRP) subunits assembly has emerged as an attractive target. Starting from a
      cycloheptathiophene-3-carboxamide derivative recently identified by us for its
      ability to disrupt the interaction between the PA and PB1 subunits of RdRP, we
      have designed and synthesized a series of analogues. Their biological evaluation
      led to the identification of more potent protein-protein interaction inhibitors,
      endowed with antiviral activity that also encompassed a number of clinical
      isolates of FluA, including an oseltamivir-resistant strain, and FluB, without
      showing appreciable toxicity. From this study, the cycloheptathiophene-3
      carboxamide scaffold emerged as being particularly suitable to impart anti-Flu
      activity. 

PMID- 24313731
TI  - Assessment of the oral health knowledge of healthcare providers in geriatric
      nursing homes: additional training needs required.
AB  - OBJECTIVES: This study was aimed at assessing the knowledge of oral health and
      training needs of health workers in geriatric nursing homes. BACKGROUND:
      Providing daily oral care to dependent elderly people is the best way to prevent
      oral disorders. Because there are no dental hygienists in France, health workers
      play an important role in providing oral care in nursing homes and should have
      correct and adequate knowledge. MATERIALS AND METHODS: Health workers from 8
      geriatric nursing homes in Puy de Dome (France) completed a 58-item
      questionnaire. Oral health knowledge regarding dental decay, periodontal
      diseases, oral hygiene and denture care was assessed. Univariate and bivariate
      analyses were performed. RESULTS: A total of 99 health workers took part in the
      study. The total mean score was significantly different if health workers had
      received training in oral disorders (49.3 +/- 11.7 vs. 43.9 +/- 10; p < 0.05) or
      in the maintenance of oral health (50.5 +/- 10.5 vs. 42.9 +/- 10; p < 0.01). The
      mean scores obtained in the 'dental decay' subsection and in the 'oral and
      denture hygiene' subsection were the lowest. CONCLUSION: Geriatric nursing home
      staff need training in understanding the impact of oral health on general health.
      Theoretical knowledge of oral diseases has to be improved in order for health
      workers to understand oral hygiene procedures and to help them identify early
      oral disorders.

PMID- 24313732
TI  - Inorganic micelles as efficient and recyclable micellar catalysts.
AB  - An "inorganic micelle" structure that has a hydrophilic cavity and hydrophobic
      surface has been synthesized. The inorganic micelles possess large surface area
      and controllable hydrophobic/hydrophilic interface. It shows high catalytic
      efficiency and great recyclability in the bromination of alcohols. This work
      suggests that inorganic micelles may be suitable for selective organic syntheses
      as well as industrial applications and demonstrates the value of translating
      nanostructure design from organic to inorganic. 

PMID- 24313733
TI  - Internet abusers associate with a depressive state but not a depressive trait.
AB  - AIM: The present study investigated three issues: (i) whether Internet abusers
      display a depressive state without a depressive trait; (ii) which symptoms are
      shared between Internet abuse and depression; and (iii) which personality
      characteristics were shown in Internet abusers. METHODS: Ninety-nine male and 58
      female participants aged 18-24 years were screened with the Chen Internet
      Addiction Scale. After screening, subjects were separated into the high- (n = 73)
      and low-risk (n = 84) Internet abuser groups. Participants were respectively
      administered the Chinese version of the Beck Depression Inventory-II to assess a
      depressive state and the Minnesota Multiphasic Personality Inventory-2 to assess
      a depressive trait. RESULTS: The present results showed that high-risk Internet
      abusers exhibited a stronger depressive state than low-risk Internet abusers in
      the Beck Depression Inventory-II. However, high-risk Internet abusers didnot show
      a depressive trait in the Minnesota Multiphasic Personality Inventory-2 compared
      to low-risk Internet abusers. Therefore, high-risk Internet abuse participants
      exhibited a depressive state without a depressive trait. CONCLUSIONS: In a
      comparison of the symptoms of depression and Internet abuse, it was found that
      high-risk Internet abuse participants shared some common behavioral mechanisms
      with depression, including the psychiatric symptoms of loss of interest,
      aggressive behavior, depressive mood, and guilty feelings. High-risk Internet
      abuse participants may be more susceptible to a temporal depressive state but not
      a permanent depressive trait. The present findings have clinical implications for
      the prevention and treatment of Internet abuse.

PMID- 24313734
TI  - Impact of DNA environment on the intrastrand cross-link lesions: hydrogen atom
      release as the last step of formation of G[8-5m]T.
AB  - Oxidative intrastrand cross-links where two nucleobases are covalently tethered
      form a particularly harmful class of DNA lesions. Their formation follows a
      radical pathway, as initiated by reactive oxygen species, which often ends with
      the departure of the hydrogen H8 of guanine to restore a closed-shell adduct. The
      ease of this abstraction step is investigated here for three systems of
      increasing complexity, C8-methyleguanine, the guanine-thymine dinucleoside
      monophosphate (GpT), and GpT embedded in a hexameric DNA sequence. First
      principle calculations, combined with semiempirical approaches for the latter
      system, are performed to determine the energetics of the intermediates and to
      compare their respective exergonicities, which turned out to significantly depend
      on the environment. The hydrogen departure path is shown to be strongly favored
      compared to usual H-abstraction sites for normal guanine, while the impact of the
      biological environment is evidenced as the H8 departure becomes more difficult
      when larger structures are considered. A computational assessment of a plausible
      oxime intermediate is discussed as well. 

PMID- 24313735
TI  - Effects of different orthodontic adhesives and resin removal techniques on enamel
      color alteration.
AB  - OBJECTIVE: To investigate the color alterations in enamel following the use of
      different orthodontic bonding resins and adhesive residue-removal burs. MATERIALS
      AND METHODS: Metal brackets were bonded to extracted human premolars (n  =  175)
      by using an etch-and-rinse adhesive system, a self-etch adhesive system (SEP), or
      a resin-modified glass ionomer cement (RMGIC). After 24 hours of photoaging, the
      brackets were removed and the adhesive residue on the tooth surfaces was cleaned
      with either a tungsten carbide bur or a Stainbuster bur. Tooth colors were
      measured with a spectrophotometer at baseline, after adhesive removal, and after
      additional photoaging. Color evaluation was made, and color differences induced
      by photoaging were calculated. Statistical evaluation was made using the Kruskal
      Wallis test and the Mann-Whitney U-test, with Bonferroni correction. RESULTS: All
      specimens showed discoloration at varying levels. The highest color change was
      observed in the etch-and-rinse adhesive/tungsten carbide bur group. When the etch
      and-rinse and self-etch adhesives were used, adhesive-remnant removal with
      Stainbuster burs resulted in significantly lower discoloration. The type of bur
      did not affect the extent of enamel discoloration in the RMGIC group.
      CONCLUSIONS: Orthodontic treatment alters the original color of enamel, and both
      the adhesive system and the resin-removal methods are responsible for this
      change. When brackets are bonded with the etch-and-rinse system or the SEP,
      cleaning the adhesive residuals with Stainbuster burs is recommended for minimal
      change. RMGIC can be safely cleaned with tungsten carbide burs.

PMID- 24313736
TI  - What is your diagnosis? Intra-abdominal mass in a female spayed dog.

PMID- 24313737
TI  - Functional characterization of Arabidopsis HsfA6a as a heat-shock transcription
      factor under high salinity and dehydration conditions.
AB  - Although heat-shock transcription factors are well characterized in the heat
      stress-related pathway, they are poorly understood in other stress responses.
      Here, we functionally characterized AtHsfA6a in the presence of exogenous
      abscisic acid (ABA) and under high salinity and dehydration conditions. AtHsfA6a
      expression under normal conditions is very low, but was highly induced by
      exogenous ABA, NaCl and drought. Unexpectedly, the levels of AtHsfA6a transcript
      were not significantly altered under heat and cold stresses. Electrophoretic
      mobility shift assays and transient transactivation assays indicated that
      AtHsfA6a is transcriptionally regulated by ABA-responsive element binding
      factor/ABA-responsive element binding protein, which are key regulators of the
      ABA signalling pathway. Additionally, fractionation and protoplast transient
      assays showed that AtHsfA6a was in cytoplasm and nucleus simultaneously; however,
      under conditions of high salinity the majority of AtHsfA6A was in the nucleus.
      Furthermore, at both seed germination and seedlings stage, plants overexpressing
      AtHsfA6a were hypersensitive to ABA and exhibited enhanced tolerance against salt
      and drought stresses. Finally, the microarray and qRT-PCR analyses revealed that
      many stress-responsive genes were up-regulated in the plants overexpressing
      AtHsfA6a. Taken together, the data strongly suggest that AtHsfA6a acts as a
      transcriptional activator of stress-responsive genes via the ABA-dependent
      signalling pathway. 

PMID- 24313738
TI  - The ICF Core Sets for hearing loss--researcher perspective. Part I: Systematic
      review of outcome measures identified in audiological research.
AB  - OBJECTIVE: To review the literature in order to identify outcome measures used in
      research on adults with hearing loss (HL) as part of the ICF Core Sets
      development project, and to describe study and population characteristics of the
      reviewed studies. DESIGN: A systematic review methodology was applied using
      multiple databases. A comprehensive search was conducted and two search pools
      were created, pool I and pool II. STUDY SAMPLE: The study population included
      adults (>= 18 years of age) with HL and oral language as the primary mode of
      communication. RESULTS: 122 studies were included. Outcome measures were
      distinguished by 'instrument type', and 10 types were identified. In total, 246
      (pool I) and 122 (pool II) different measures were identified, and only
      approximately 20% were extracted twice or more. Most measures were related to
      speech recognition. Fifty-one different questionnaires were identified. Many
      studies used small sample sizes, and the sex of participants was not revealed in
      several studies. CONCLUSION: The low prevalence of identified measures reflects a
      lack of consensus regarding the optimal outcome measures to use in audiology.
      Reflections and discussions are made in relation to small sample sizes and the
      lack of sex differentiation/descriptions within the included articles.

PMID- 24313739
TI  - Anticonvulsant medications for panic disorder: a review and synthesis of the
      evidence.
AB  - OBJECTIVES: Currently, there are no guidelines for when to use an antiepileptic
      drug (AED) in nonepileptic panic disorder (PD) patients. We conducted this review
      to ascertain what guidance available literature can provide as to when to
      consider AEDs for PD patients. METHODS: The primary data sources were PubMed and
      Google-Scholars. Search was limited to "English" and "Humans". Only papers
      addressing use of nonbenzodiazepine AEDs in PD were included. Data regarding
      study subjects, the AED utilized, and clinical responses were collected. EEG data
      were used to classify reports of patients with abnormal versus those with normal
      and/or no EEG work-up. RESULTS: Ten reports were identified for use of AEDs in PD
      patients with abnormal EEGs with a total of 20 patients (17 responders). None of
      the 10 reports were controlled studies. Eighteen reports were identified for use
      of AEDs in panic patients with either normal EEGs or unselected groups (no EEG
      work-up). Out of the 18 reports, three were controlled studies. Included in the
      18 studies were 253 patients (137 responders). CONCLUSIONS: We preliminary
      concluded that EEG work-up could be useful in guiding the treatment in PD as an
      abnormal EEG may be indicative of a higher likelihood of a positive response to
      an AED.

PMID- 24313740
TI  - Oral and systemic photoprotection.
AB  - Photoprotection can be provided not only by ultraviolet (UV) blockers but also by
      oral substances. Epidemiologically identified associations between foods and skin
      cancer and interventional experiments have discovered mechanisms of UV skin
      damage. These approaches have identified oral substances that are photoprotective
      in humans. UV inhibits adenosine triphosphate (ATP) production causing an energy
      crisis, which prevents optimal skin immunity and DNA repair. Enhancing ATP
      production with oral nicotinamide protects from UV immunosuppression, enhances
      DNA repair and reduces skin cancer in humans. Reactive oxygen species also
      contribute to photodamage. Nontoxic substances consumed in the diet, or available
      as oral supplements, can protect the skin by multiple potential mechanisms. These
      substances include polyphenols in fruit, vegetables, wine, tea and caffeine
      containing foods. UV-induced prostaglandin E2 (PGE2 ) contributes to photodamage.
      Nonsteroidal anti-inflammatory drugs and food substances reduce production of
      this lipid mediator. Fish oils are photoprotective, at least partially by
      reducing PGE2 . Orally consumed substances, either in the diet or as supplements,
      can influence cutaneous responses to UV. A current research goal is to develop an
      oral supplement that could be used in conjunction with other sun protective
      strategies in order to provide improved protection from sunlight.

PMID- 24313741
TI  - Tubulin inhibitors: a patent review.
AB  - INTRODUCTION: Microtubules play an important role in several cellular processes,
      particularly in the formation of the mitotic spindle during the process of
      mitosis. These highly dynamic mitotic-spindle microtubules have become a
      successful target of cancer therapy. Microtubule-targeting agents, such as vinca
      alkaloids and taxanes, were used in clinic over 50 years. In past decades,
      development of new antimicrotubule agents that possess different structure and
      binding sites of tubulin has shown potent activity against the proliferation of
      various cancer cells, as well as in multidrug-resistant cancers. Interestingly,
      many of these agents represent an attractive ability that targeting the tumor
      blood vessels results in tumor vascular disruption. Therefore, exploring new
      agents and strategies may provide more effective therapeutic options in the
      related treatment of cancer. AREAS COVERED: In past few years, there are many
      chemical compounds that successfully interferes the microtubules and display
      antitumor effect. In these, published compounds supply the fresh minds in
      modification of present drugs and new insights into the development of tubulin
      inhibitors. EXPERT OPINION: This article arranges the microtubule-targeting
      agents that have published in patent in recent years. It may help in the
      investigation of new tubulin binding site and development of novel drug candidate
      in the future.

PMID- 24313742
TI  - Palladium-catalyzed meta-selective C-H bond activation with a nitrile-containing
      template: computational study on mechanism and origins of selectivity.
AB  - Density functional theory investigations have elucidated the mechanism and
      origins of meta-regioselectivity of Pd(II)-catalyzed C-H olefinations of toluene
      derivatives that employ a nitrile-containing template. The reaction proceeds
      through four major steps: C-H activation, alkene insertion, beta-hydride
      elimination, and reductive elimination. The C-H activation step, which proceeds
      via a concerted metalation-deprotonation (CMD) pathway, is found to be the rate-
      and regioselectivity-determining step. For the crucial C-H activation, four
      possible active catalytic species-monomeric Pd(OAc)2, dimeric Pd2(OAc)4,
      heterodimeric PdAg(OAc)3, and trimeric Pd3(OAc)6-have been investigated. The
      computations indicated that the C-H activation with the nitrile-containing
      template occurs via a Pd-Ag heterodimeric transition state. The nitrile directing
      group coordinates with Ag while the Pd is placed adjacent to the meta-C-H bond in
      the transition state, leading to the observed high meta-selectivity. The
      Pd2(OAc)4 dimeric mechanism also leads to the meta-C-H activation product but
      with higher activation energies than the Pd-Ag heterodimeric mechanism. The Pd
      monomeric and trimeric mechanisms require much higher activation free energies
      and are predicted to give ortho products. Structural and distortion energy
      analysis of the transition states revealed significant effects of distortions of
      the template on mechanism and regioselectivity, which provided hints for further
      developments of new templates. 

PMID- 24313743
TI  - Surface functionalization of zirconium phosphate nanoplatelets for the design of
      polymer fillers.
AB  - Inorganic-organic hybrid materials were synthesized by covalent attachment of
      epoxides to the surface of zirconium phosphate (ZrP) nanoplatelets. X-ray powder
      diffraction, FTIR, and TGA were utilized to confirm the presence of the modifiers
      and exclusive functionalization of the ZrP surface. NMR experiments were
      conducted to confirm the formation of P-O-C bonds between surface phosphate
      groups and epoxide rings. The applicability of the organically modified products
      was demonstrated by their use as fillers in a polymer matrix. Subsequently, a two
      step intercalation and surface modification procedure was utilized to prepare
      polymer nanocomposites that were imparted with functionality through the
      encapsulation of molecules within the interlayer of surface modified ZrP. 

PMID- 24313744
TI  - Nondestructive imaging of plant-parasitic nematode development and host response
      to nematode pathogenesis.
AB  - The secluded lifestyle of endoparasitic plant nematodes hampers progress toward a
      comprehensive understanding of plant-nematode interactions. A novel technique
      that enables nondestructive, long-term observations of a wide range of live
      nematodes in planta is presented here. As proof of principle, Pratylenchus
      penetrans, Heterodera schachtii, and Meloidogyne chitwoodi were labeled
      fluorescently with PKH26 and used to infect Arabidopsis thaliana grown in
      microscopy rhizosphere chambers. Nematode behavior, development, and morphology
      were observed for the full duration of each parasite's life cycle by confocal
      microscopy for up to 27 days after inoculation. PKH26 accumulated in intestinal
      lipid droplets and had no negative effect on nematode infectivity. This technique
      enabled visualization of Meloidogyne gall formation, nematode oogenesis, and
      nematode morphological features, such as the metacorpus, vulva, spicules, and
      cuticle. Additionally, microscopy rhizosphere chambers were used to characterize
      plant organelle dynamics during M. chitwoodi infection. Peroxisome abundance
      strongly increased in early giant cells but showed a marked decrease at later
      stages of feeding site development, which suggests a modulation of plant
      peroxisomes by root-knot nematodes during the infection process. Taken together,
      this technique facilitates studies aimed at deciphering plant-nematode
      interactions at the cellular and subcellular level and enables unprecedented
      insights into nematode behavior in planta.

PMID- 24313745
TI  - Adverse effects associated with high-dose olanzapine therapy in patients admitted
      to inpatient psychiatric care.
AB  - CONTEXT: In 2012, Danish psychiatrist raised concerns regarding the use of high
      dose olanzapine in the treatment of patients. The present study was part of an
      audit carried out by the Mental Health Services of the Capitol Region of Denmark
      regarding this topic. Objective. To assess the potential risks associated with
      high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units.
      METHODS: The study was an observational case series based on review of patient
      charts. The main inclusion criterion was treatment with at least one daily dose >
      40 mg olanzapine during the index admission in the period between 1st of January
      and 15th of March 2012. Six additional criteria were applied in order to target
      the subgroup of patients most likely to have experienced an adverse event due to
      treatment with olanzapine. The physician order entry system and the central
      patient register containing patient specific information about diagnoses and
      treatments were used for identification of study population. RESULTS: The 91
      patients included in the study received maximum daily doses of olanzapine ranging
      from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded
      2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were
      the most frequent adverse events with frequencies of 27% and 25%, respectively.
      Furthermore, other well-known adverse events such as weight gain (14%),
      hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval
      (QTc) prolongation (1%) were also observed in some patients. Five patients died
      and in two of these cases, olanzapine was concluded to be a possible contributing
      cause of death. CONCLUSION: Increased frequency of extrapyramidal symptoms and
      sedation as well as severe toxicity was observed in patients treated with up to
      160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians
      should be ready to act appropriately if toxic effects of olanzapine occur.
      Treatment cessation should be immediate if serious adverse events such as
      neuroleptic malignant syndrome arise.

PMID- 24313746
TI  - DART-MS as a preliminary screening method for "herbal incense": chemical analysis
      of synthetic cannabinoids.
AB  - Direct analysis in real time mass spectrometry (DART-MS) served as a method for
      rapid high-throughput screening of six commercially available "Spice" products,
      detecting various combinations of five synthetic cannabinoids. Direct analysis in
      real time is an ambient ionization process that, along with high mass accuracy
      time-of-flight (TOF)-MS to 0.0001 Da, was employed to establish the presence of
      cannabinoids. Mass spectra were acquired by simply suspending a small portion of
      sample between the ion source and the mass spectrometer inlet. The ability to
      test minute amounts of sample is a major advantage when very limited amounts of
      evidentiary material are available. In addition, reports are widespread regarding
      the testing backlogs that now exist because of the large influx of designer
      drugs. This method circumvents time-consuming sample extraction, derivatization,
      chromatographic, and other sample preparative steps required for analysis by more
      conventional mass spectrometric methods. Accordingly, the synthetic cannabinoids
      AM-2201, JWH-122, JWH-203, JWH-210, and RCS-4 were identified in commercially
      available herbal Spice products, singly and in tandem, at concentrations within
      the range of 4-141 mg/g of material. Direct analysis in real time mass
      spectrometry decreases the time necessary to triage analytical evidence, and
      therefore, it has the potential to contribute to backlog reduction and more
      timely criminal prosecution. 

PMID- 24313749
TI  - Walking phase modulates H-reflex amplitude in flexor carpi radialis.
AB  - It is well established that remote whole-limb rhythmic movement (e.g., cycling or
      stepping) induces suppression of the Hoffman (H-) reflex evoked in stationary
      limbs. However, the dependence of reflex amplitude on the phase of the movement
      cycle (i.e., phase-dependence) has not been consistent across this previous
      research. The authors investigated the phase-dependence of flexor carpi radialis
      (FCR) H-reflex amplitudes during active walking and in kinematically matched
      static postures across the gait cycle. FCR H-reflexes were elicited in the
      stationary forearm with electrical stimulation to the median nerve. Significant
      phase-dependent modulation occurred during walking when the gait cycle was
      examined with adequate phase resolution. The suppression was greatest during
      midstance and midswing, suggesting increased ascending communication during these
      phases. There was no phase-dependent modulation in static standing postures and
      no correlation between lower limb background electromyography levels and H-reflex
      amplitude during active walking. This evidence, along with previous research
      demonstrating no phase modulation during passive walking, suggests that afferent
      feedback associated with joint position and leg muscle activation levels are not
      the sole source of the phase modulation seen during active walking. Possible
      sources of phase modulation include combinations of afferent feedback related to
      active movement or central motor commands or both.

PMID- 24313748
TI  - Gene-expression profile and localization of Na+/K(+)-ATPase in rat enamel organ
      cells.
AB  - The sodium pump Na(+)/K(+)-ATPase, expressed in virtually all cells of higher
      organisms, is involved in establishing a resting membrane potential and in
      creating a sodium gradient to facilitate a number of membrane-associated
      transport activities. Na(+)/K(+)-ATPase is an oligomer of alpha, beta, and gamma
      subunits. Four unique genes encode each of the alpha and beta subunits. In dental
      enamel cells, the spatiotemporal expression of Na(+)/K(+)-ATPase is poorly
      characterized. Using the rat incisor as a model, this study provides a
      comprehensive expression profile of all four alpha and all four beta Na(+)/K(+)
      ATPase subunits throughout all stages of amelogenesis. Real-time PCR, western
      blot analysis, and immunolocalization revealed that alpha1, beta1, and beta3 are
      expressed in the enamel organ and that all three are most highly expressed during
      late-maturation-stage amelogenesis. Expression of beta3 was significantly higher
      than expression of beta1, suggesting that the dominant Na(+)/K(+)-ATPase consists
      of an alpha1beta3 dimer. Localization of alpha1, beta1, and beta3 subunits in
      ameloblasts was primarily to the cytoplasm and occasionally along the basolateral
      membranes. Weaker expression was also noted in papillary layer cells during early
      maturation. Our data support that Na(+)/K(+)-ATPase is functional in maturation
      stage ameloblasts.

PMID- 24313751
TI  - Theranostics in the growing field of personalized medicine: an analytical
      chemistry perspective.

PMID- 24313750
TI  - Impact of cyclic stretch on induced elastogenesis within collagenous conduits.
AB  - In vitro tissue engineering of vascular conduits requires a synergy between
      several external factors, including biochemical supplementation and
      mechanotranductive stimulation. The goal of this study was to improve adult human
      vascular smooth muscle cell orientation and elastic matrix synthesis within 3D
      tubular collagen gel constructs. We used a combination of elastogenic factors
      (EFs) previously tested in our lab, along with cyclic circumferential strains at
      low amplitude (2.5%) delivered at a range of frequencies (0.5, 1.5, and 3 Hz).
      After 21 days of culture, the constructs were analyzed for elastic matrix
      outcomes, activity of matrix metalloproteinases (MMPs)-2 and -9, cell densities
      and phenotype, and mechanical properties of constructs. While cell densities
      remained unaffected by the addition of stretch, contractile phenotypic markers
      were elevated in all stretched constructs relative to control. Constructs
      cultured with EFs stretched at 1.5 Hz exhibited the maximum elastin mRNA
      expression and total matrix elastin (over sixfold vs. the static EFs control).
      MMP-2 content was comparable in all treatment conditions, but MMP-9 levels were
      elevated at the higher frequencies (1.5 and 3 Hz). Minimal circumferential
      orientation was achieved and the mechanical properties remained comparable among
      the treatment conditions. Overall, constructs treated with EFs and stretched at
      1.5 Hz exhibited the most elastogenic outcomes. 

PMID- 24313747
TI  - Underscoring the influence of inorganic chemistry on nuclear imaging with
      radiometals.
AB  - Over the past several decades, radionuclides have matured from largely esoteric
      and experimental technologies to indispensible components of medical diagnostics.
      Driving this transition, in part, have been mutually necessary advances in
      biomedical engineering, nuclear medicine, and cancer biology. Somewhat unsung has
      been the seminal role of inorganic chemistry in fostering the development of new
      radiotracers. In this regard, the purpose of this Forum Article is to more
      visibly highlight the significant contributions of inorganic chemistry to nuclear
      imaging by detailing the development of five metal-based imaging agents: (64)Cu
      ATSM, (68)Ga-DOTATOC, (89)Zr-transferrin, (99m)Tc-sestamibi, and (99m)Tc
      colloids. In a concluding section, several unmet needs both in and out of the
      laboratory will be discussed to stimulate conversation between inorganic chemists
      and the imaging community. 

PMID- 24313752
TI  - An evaluation of the effectiveness of engaging Canadian clients as partners in in
      home care.
AB  - This exploratory quasi-experimental evaluation assessed the effectiveness of the
      use of a concrete discussion guide to promote organisation-wide application of a
      partnering approach to engage older home-care clients with chronic
      disease/disabilities as care partners. A post-test-only design with an
      independent pre-test sample was used to compare selected outcomes with those of
      standard in-home care. The theoretically informed discussion guide portrayed how
      to go about the process of empowering partnering by using language and open-ended
      conversational leads to construct partnering, partnering effort and health as a
      resource for everyday living through social interaction. The discussion guide was
      provided to all providers for use with all clients in one home-care programme in
      Ontario, Canada and this organisation was compared with a similar but
      geographically distanced organisation, also in Ontario. Seven hundred and ninety
      one randomly selected clients (mean age = 72.5 years) receiving 3+ months of in
      home care for chronic conditions/disabilities from the two home-care programmes
      between September 2007 and May 2010 completed a researcher-administered
      questionnaire at either baseline, 1 year or 2 years. Instruments included the
      Client's Partnering Experience, Health-Promoting Partnering Effort, a modified
      version of Locus of Authority in Decision-Making, the Medical Outcomes Survey
      Self-Rated Health Scale, Health and Social Services Utilization and a modified
      Functional Independence Measure. Analysis of covariance revealed that the use of
      the concrete discussion guide to promote organisation-wide application of a
      partnering approach achieved significantly greater client partnering experience
      and health-promoting partnering effort over time than did the usual approach to
      in-home-care interactions. Using the discussion guide enhanced client/provider
      partnering, hence, interdependence, contributing positively to promoting clients'
      health as a resource for everyday living.

PMID- 24313753
TI  - Attenuated benzodiazepine-sensitive tonic GABAA currents of supraoptic
      magnocellular neuroendocrine cells in 24-h water-deprived rats.
AB  - In supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs), gamma
      GABA, via activation of GABAA receptors (GABAA Rs), mediates persistent tonic
      inhibitory currents (Itonic ), as well as conventional inhibitory postsynaptic
      currents (IPSCs, Iphasic ). In the present study, we examined the functional
      significance of Itonic in SON MNCs challenged by 24-h water deprivation (24WD).
      Although the main characteristics of spontaneous IPSCs were similar in 24WD
      compared to euhydrated (EU) rats, Itonic , measured by bicuculline (BIC)-induced
      Iholding shifts, was significantly smaller in 24WD compared to EU rats (P <
      0.05). Propofol and diazepam prolonged IPSC decay time to a similar extent in
      both groups but induced less Itonic in 24WD compared to EU rats, suggesting a
      selective decrease in GABAA receptors mediating Itonic over Iphasic in 24WD rats.
      THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a preferential delta
      subunit agonist, and L-655,708, a GABAA receptor alpha5 subunit selective
      imidazobenzodiazepine, caused a significantly smaller inward and outward shift in
      Iholding , respectively, in 24WD compared to EU rats (P < 0.05 in both cases),
      suggesting an overall decrease in the alpha5 subunit-containing GABAA Rs and the
      delta subunit-containing receptors mediating Itonic in 24WD animals. Consistent
      with a decrease in 24WD Itonic , bath application of GABA induced significantly
      less inhibition of the neuronal firing activity in 24WD compared to EU SON MNCs
      (P < 0.05). Taken together, the results of the present study indicate a selective
      decrease in GABAA Rs functions mediating Itonic as opposed to those mediating
      Iphasic in SON MNCs, demonstrating the functional significance of Itonic with
      respect to increasing neuronal excitability and hormone secretion in 24WD rats.

PMID- 24313755
TI  - Nanoparticles strengthen intracellular tension and retard cellular migration.
AB  - Nanoparticles can have profound effects on cell biology. Here, we show that after
      TiO2, SiO2, and hydroxyapatite nanoparticles treatment, TR146 epithelial cell
      sheet displayed slower migration. Cells after exposure to the nanoparticles
      showed increased cell contractility with significantly impaired wound healing
      capability however without any apparent cytotoxicity. We showed the mechanism is
      through nanoparticle-mediated massive disruption of the intracellular microtubule
      assembly, thereby triggering a positive feedback that promoted stronger substrate
      adhesions thus leading to limited cell motility. 

PMID- 24313754
TI  - [1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains.
AB  - Bromodomains are gaining increasing interest as drug targets. Commercially
      sourced and de novo synthesized substituted [1,2,4]triazolo[4,3-a]phthalazines
      are potent inhibitors of both the BET bromodomains such as BRD4 as well as
      bromodomains outside the BET family such as BRD9, CECR2, and CREBBP. This new
      series of compounds is the first example of submicromolar inhibitors of
      bromodomains outside the BET subfamily. Representative compounds are active in
      cells exhibiting potent cellular inhibition activity in a FRAP model of CREBBP
      and chromatin association. The compounds described are valuable starting points
      for discovery of selective bromodomain inhibitors and inhibitors with mixed
      bromodomain pharmacology.

PMID- 24313756
TI  - Increased subsequent risk of acute coronary syndrome for patients with depressive
      disorder: a nationwide population-based retrospective cohort study.
AB  - AIM: The purpose of this study was to explore the possible association between
      subsequent acute coronary syndrome (ACS) risk and depressive disorder. METHODS:
      We used data from the National Health Insurance system of Taiwan to address the
      research topic. The exposure cohort contained 10 871 patients with new diagnoses
      of depressive disorders. Each patient was randomly frequency-matched for sex and
      age with four participants from the general population who did not have any ACS
      history before the index date (control group). Cox's proportion hazard regression
      analyses were conducted to estimate the relation between depressive disorders and
      subsequent ACS risk. RESULTS: Among patients with depressive disorders, the
      overall risk for developing subsequent ACS was significantly higher than that of
      the control group (adjusted hazard ratio: 1.88, 95% confidence interval: 1.63
      2.17). Further analysis revealed that the higher risk was observed in patients
      who were male, were of older age, or whose diagnosis was combined with other
      comorbidities. CONCLUSIONS: The findings from this population-based retrospective
      cohort study suggest that depressive disorder is associated with an increased
      subsequent ACS risk.

PMID- 24313758
TI  - Purpose of the conference.

PMID- 24313757
TI  - 5-Methylation of cytosine in CG:CG base-pair steps: a physicochemical mechanism
      for the epigenetic control of DNA nanomechanics.
AB  - van der Waals density functional theory is integrated with analysis of a non
      redundant set of protein-DNA crystal structures from the Nucleic Acid Database to
      study the stacking energetics of CG:CG base-pair steps, specifically the role of
      cytosine 5-methylation. Principal component analysis of the steps reveals the
      dominant collective motions to correspond to a tensile "opening" mode and two
      shear "sliding" and "tearing" modes in the orthogonal plane. The stacking
      interactions of the methyl groups globally inhibit CG:CG step overtwisting while
      simultaneously softening the modes locally via potential energy modulations that
      create metastable states. Additionally, the indirect effects of the methyl groups
      on possible base-pair steps neighboring CG:CG are observed to be of comparable
      importance to their direct effects on CG:CG. The results have implications for
      the epigenetic control of DNA mechanics. 

PMID- 24313759
TI  - Chair's summary: Mechanisms of relevance to clinical heterogeneity of asthma and
      chronic obstructive pulmonary disease.

PMID- 24313762
TI  - Phenotypes and disease characterization in chronic obstructive pulmonary disease.
      Toward the extinction of phenotypes?
AB  - Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous disease.
      The severity of airflow limitation, traditionally used to guide therapy in
      patients with COPD, does not describe this complexity properly. As a result, over
      the past few years there has been a great deal of interest in characterizing COPD
      more precisely and identifying homogeneous groups of patients who respond to
      specific therapeutic interventions (i.e., phenotypes). This review summarizes a
      presentation at the Transatlantic Airway Conference held in Lucerne on January
      31, 2013 on this topic. It addresses the following questions: (1) What do we mean
      by "phenotypes"? (2) Why do we care about them? (3) Are phenotypes the best
      strategy to understand COPD heterogeneity? and (4) How can we progress in this
      field? 

PMID- 24313760
TI  - How variability in clinical phenotypes should guide research into disease
      mechanisms in asthma.
AB  - Asthma is increasingly being considered as a collection of different phenotypes
      that present with intermittent wheezing. Unbiased approaches to classifying
      asthma have led to the identification of distinct phenotypes based on age of
      onset of disease, atopic state, disease severity or activity, degree of chronic
      airflow obstruction, and sputum eosinophilia. Linking phenotypes to known disease
      mechanism is likely to be more fruitful in determining the potential targets
      necessary for successful therapies of specific endotypes. A "Th2-high expression"
      signature from the epithelium of patients with asthma identifies a subset of
      patients with high eosinophilia and good therapeutic responsiveness to
      corticosteroids. Other characteristic traits of asthma include noneosinophilic
      asthma, corticosteroid insensitivity, obesity-associated, and exacerbation-prone.
      Further progress into asthma mechanisms will be driven by unbiased data
      integration of multiscale data sets from omics technologies with those phenotypic
      characteristics and by using mathematical modeling. This will lead to the
      discovery of new pathways and their integration into endotypes and also set up
      further hypothesis-driven research. Continued iteration through experimentation
      or modeling will be needed to refine the phenotypes that relate to outcomes and
      also delineate specific treatments for specific phenotypes. 

PMID- 24313763
TI  - Clinical correlations of computed tomography imaging in chronic obstructive
      pulmonary disease.
AB  - Chronic obstructive pulmonary disease is a complex disease with heterogeneous
      presentation, progression, and structural abnormality that is currently graded
      solely on clinical and physiologic parameters. Thoracic computed tomography
      imaging holds promise for phenotyping in chronic obstructive pulmonary disease,
      but despite increasing availability, this methodology has yet to be incorporated
      into clinical guidelines or routine clinical practice. However, the unique
      clinical implications of emphysema and airways disease are becoming clearer.
      Emphysema has a strong association with more rapid disease progression and
      mortality. Airways disease has a strong relationship with symptoms and health
      status. It is hoped that future refinement of emphysema assessment allowing for
      quantitative subtyping will also increase our ability to define clinically
      meaningful subgroups, as will development of methodologies to assess airways
      disease and, in particular, small airways through inspiratory/expiratory image
      registration techniques. Most important, however, is the need for longitudinal
      data, in not only observational but also therapeutic settings, such that the
      impact of interventions on radiographically defined phenotypes can be assessed. 

PMID- 24313761
TI  - Clinical heterogeneity in the severe asthma research program.
AB  - The National Heart, Lung, and Blood Institute has sponsored several asthma
      clinical networks, but the Severe Asthma Research Program (SARP) is unique,
      because it is not a clinical trials network, and it includes both adults and
      children. Investigators in SARP have comprehensively characterized 1,644 patients
      with asthma over the past 10 years, including 583 individuals with severe asthma
      and 300 children below the age of 18 years. The diversity in clinical
      characteristics, physiologic measures, and biomarkers in a large number of
      subjects across the ages provides an ideal cohort in which to investigate asthma
      heterogeneity. Using both biased and unbiased approaches, multiple asthma
      phenotypes have been described in SARP. These phenotypic analyses have improved
      our understanding of heterogeneity in asthma, and may provide a starting point to
      transform clinical practice through the evidence-based classification of disease
      severity. Although these new phenotypes strive to make order out of a
      heterogeneous group of patients, they are limited by that heterogeneity. There
      may be large groups of patients, especially those with milder asthma, that can be
      grouped into a clinical phenotype to guide therapy, but there will always be
      patients on the "edge" of a phenotype who will not fit into these groupings. In
      the SARP cluster analysis, subjects on the "edge" of a phenotype frequently had
      lung function that was better or worse than other subjects in the same cluster,
      despite similar clinical characteristics. This suggests that different
      pathophysiologic mechanisms may be responsible for decrements in lung function in
      some subjects. This is extremely important for subjects with severe asthma who
      may be on the "edge" of two phenotypes that may be driven by different
      pathobiologic mechanisms that warrant different therapeutic approaches. 

PMID- 24313764
TI  - Obesity and asthma.
AB  - There is a global epidemic of asthma and obesity that is concentrated in
      Westernized and developed countries. A causal association in some people with
      asthma is suggested by observations that obesity precedes the onset of asthma and
      that bariatric surgery for morbid obesity can resolve asthma. The obese asthma
      phenotype features poor asthma control, limited response to corticosteroids, and
      an exaggeration of the physiological effects of obesity on lung function, which
      includes a reduction in expiratory reserve volume and airway closure occurring
      during tidal breathing. Obesity has important implications for asthma treatment.
      Increasing corticosteroid doses based on poor asthma control, as currently
      recommended in guidelines, may lead to overtreatment with corticosteroids in
      obese asthma. Enhanced bronchodilation, particularly of the small airways, may
      reduce the component of airway closure due to increased bronchomotor tone and
      suggests that greater emphasis should be placed on long-acting bronchodilators in
      obese asthma. The societal implications of this are important: with increasing
      obesity there will be increasing asthma from obesity, and the need to identify
      successful individual and societal weight-control strategies becomes a key goal. 

PMID- 24313765
TI  - Eosinophilic phenotypes of airway disease.
AB  - Our understanding of the clinical implications of eosinophilic airway
      inflammation has increased significantly over the last 20 years, aided by the
      development of noninvasive means to assess it. This pattern of airway
      inflammation can occur in a diverse range of airway diseases. It is associated
      with a positive response to corticosteroids and a high risk of preventable
      exacerbations. Our new understanding of the role of eosinophilic airway
      inflammation has paved the way for the clinical development of a number of more
      specific inhibitors that may become new treatment options. Different definitions,
      ideas of disease, and adoption of biomarkers that are not well known are
      necessary to fully realize the potential of these treatments. 

PMID- 24313766
TI  - Oxidative stress in airway diseases.
AB  - Airway oxidative stress is broadly defined as an imbalance between prooxidative
      and antioxidative processes in the airway. Given its direct exposure to the
      environment, the lung has several mechanisms to prevent an excessive degree of
      oxidative stress. Both enzymatic and nonenzymatic systems can buffer a wide range
      of reactive oxidative species and other compounds with oxidative potential. In
      diseases like asthma and chronic obstructive lung disease, airway oxidative
      stress can occur from a number of sources, including greater exposure to
      environmental prooxidants, airway infiltration of inflammatory cells, metabolic
      deregulation, and reduced levels of antioxidants. Airway oxidative stress has
      been associated with worse disease severity, reduced lung function, and
      epigenetic changes that can diminish response to steroids. Although oxidative
      stress has been linked to a wide range of adverse biological effects, it has also
      been associated with adaptive responses and with resolution of inflammation.
      Therefore, more than being an imbalance with a predictable threshold after which
      disease or injury ensues, oxidative stress is a dynamic and continuous process.
      This might explain why supplementing antioxidants has largely failed to improve
      diseases such as asthma and chronic obstructive pulmonary disease. However, the
      therapeutic potential of antioxidants could be greatly improved by taking an
      approach that considers individual and environmental risk factors, instead of
      treating oxidative airway stress broadly. 

PMID- 24313767
TI  - Mast cells, their subtypes, and relation to asthma phenotypes.
AB  - Mast cells (MCs) are among the first cell types associated with allergies and
      asthma. Studies in human asthma have identified their presence in the lung
      submucosa and smooth muscle and also in the airway epithelium. As our
      understanding of the distribution and location of these MCs in the human airway
      has increased, it is clear that much remains to be understood regarding the
      presence and subtype of these MCs in relationship to asthma phenotypes, defined
      both clinically and on the basis of immunologic pathways. Human MCs have
      traditionally been divided into two major subtypes based on the protease granule
      content, with tryptase representing total MCs. There is emerging evidence that in
      the epithelium, MCs of an altered subtype (with tryptase, chymase, and/or
      carboxypeptidase A3) may play a role in the pathophysiology of poorly controlled,
      severe, Th2-associated asthma. 

PMID- 24313768
TI  - Influences of the microbiome on the early origins of allergic asthma.
AB  - During and immediately after birth, neonates are exposed to an environment laden
      with bacteria, a stark contrast to the sterile environment of the womb. Over the
      ensuing weeks and months, environmental microbial communities colonize their new
      host, and subsequent host-microbial cross-talk provides key developmental signals
      for the host's immune system. Emerging data from epidemiological and cellular
      research studies suggest that the nature of this cross-talk might be an
      underlying factor for the development, maintenance, and exacerbation of chronic
      lung diseases, such as asthma and chronic obstructive pulmonary disease. This
      review describes recent findings concerning the bacterial microbiota in the
      airways and places these data within the context of epidemiological and
      experimental studies that allude to the functional significance of host-microbial
      cross-talk in pulmonary inflammation. 

PMID- 24313770
TI  - Altered macrophage function in chronic obstructive pulmonary disease.
AB  - The observation that macrophages are increased in chronic obstructive pulmonary
      disease (COPD) and are associated with COPD severity has led to a large number of
      studies on macrophage function in COPD. These studies have provided evidence that
      these cells contribute to tissue injury through the release of various mediators,
      including proteases such as matrix metalloprotease-12. In addition, it was found
      that macrophages in COPD have an impaired ability to clear respiratory pathogens
      and apoptotic cells. Macrophage phagocytic function in COPD can be restored at
      least in part, as shown by in vitro studies. In a search to further understand
      this altered function of macrophages in COPD, several studies have used a range
      of markers to phenotype macrophages in COPD. Macrophages constitute a
      heterogeneous cell population, and, currently, proinflammatory M1 and anti
      inflammatory M2 and M2-like cells are considered to represent the extremes of a
      pattern of macrophage polarization. In COPD, there is no clear evidence for a
      predominance of one of these phenotypes, and an intermediate phenotype may be
      present. Future studies are needed to establish the nature of this apparent COPD
      specific macrophage subset, and to link macrophage dysfunction to COPD
      phenotypes. 

PMID- 24313769
TI  - Significance of the microbiome in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is one of few chronic disorders with
      rising mortality and morbidity. It is a highly prevalent disorder, characterized
      by highly heterogeneous clinical symptoms, health status, and disease
      progression. COPD is also characterized by an inflammatory/immune response that
      persists despite smoking cessation and varies by the patient population, method
      of assessment, and timing of measurement. Bacterial colonization or infection is
      ubiquitous in patients with COPD and, until recently, has been predominantly
      assessed using culture-based methodologies. This colonization has been believed
      to be biologically relevant. It has been estimated that more than 70% of the
      bacterial species on body surfaces cannot be cultured by standard techniques. As
      such, advanced culture-independent techniques have been developed that target
      bacterial genes, such as the 16S ribosomal RNA gene, that function as molecular
      chronometers. Application of these techniques in patients with COPD has suggested
      microbial diversity that varies by age, disease severity, and medication use. All
      of these data provide unique and rapidly evolving insight into the potential role
      of the respiratory microbiome in disease genesis and expression. 

PMID- 24313771
TI  - Subtypes of asthma defined by epithelial cell expression of messenger RNA and
      microRNA.
AB  - Human asthma can be subcategorized in several ways, but one powerful approach is
      to subtype asthma on the basis of underlying cellular and molecular mechanisms.
      Groups of patients with a disease that share a common underlying biology are
      termed an "endotype." Endotypes of asthma have been studied at both the cellular
      level (by cytological examination of induced sputum) and, increasingly, at the
      molecular level. Genome-wide analyses of mRNA expression within the lung have
      been useful in the identification of molecular endotypes of asthma and point to
      protein biomarkers of those endotypes that can be measured in the blood. More
      recently, studies of microRNA expression in airway epithelial cells in asthma
      have identified additional candidate biomarkers of asthma endotypes. One
      potentially valuable property of microRNAs is that they can also be measured in
      extracellular fluids and therefore have the potential to serve directly as
      noninvasively measured biomarkers. 

PMID- 24313772
TI  - Personalized management of chronic obstructive pulmonary disease via
      transcriptomic profiling of the airway and lung.
AB  - Chronic obstructive pulmonary disease (COPD) is a clinically heterogeneous
      disease composed of variable degrees of airflow obstruction, emphysematous
      destruction, and small airway wall thickening. The natural history of this
      disease, although generally characterized by continued decline in lung function,
      is also highly variable. Novel transcriptomic approaches to study the airway and
      lung tissue in COPD hold the potential to improve our understanding of the
      molecular mechanisms underlying this heterogeneity and identify molecular
      subtypes of disease that have similar clinical manifestations. This new
      understanding can be leveraged to develop targeted COPD therapies and ultimately
      personalize treatment of COPD based on each patient's specific molecular
      subphenotype. 

PMID- 24313773
TI  - Toward composite molecular signatures in the phenotyping of asthma.
AB  - The complex biology of respiratory diseases such as asthma is feeding the
      discovery of various disease phenotypes. Although the clinical management of
      asthma phenotypes by using a single biomarker (e.g., sputum eosinophils) is
      successful, emerging evidence shows the requirement of multiscale, high
      dimensional biological and clinical measurements to capture the complexity of
      various asthma phenotypes. High-throughput "omics" technologies, including
      transcriptomics, proteomics, lipidomics, and metabolomics, are increasingly
      standardized for biomarker discovery in asthma. The leading principle is obeying
      available guidelines on omics analysis, thereby strictly limiting false
      discovery. In this review we address the concept of transcriptomics using
      microarrays or next-generation RNA sequencing and their applications in asthma,
      highlighting the strengths and limitations of both techniques, and review
      metabolomics in exhaled air (breathomics) as a noninvasive alternative for
      sampling the airways directly. These developments will inevitably lead to the
      integration of molecular signatures in the phenotyping of asthma and other
      diseases. 

PMID- 24313774
TI  - Noninvasive biomarkers that predict treatment benefit from biologic therapies in
      asthma.
AB  - Although human asthma is commonly regarded as an allergic disorder characterized
      by type 2 cytokine expression and eosinophilic inflammation in the airways, it is
      clearly heterogeneous with respect to airway inflammation. Genomic approaches
      have identified heterogeneous gene expression patterns in asthmatic airways
      corresponding to the degree of type 2 cytokine expression and eosinophilic
      inflammation. These gene expression patterns have led to the identification of
      candidate biomarkers of eosinophilic airway inflammation that do not require
      bronchoscopy or sputum induction. Candidate biologic therapies targeting
      mediators of type 2 airway inflammation have progressed through clinical studies
      in patients with moderate-severe asthma in recent years. Serum periostin,
      fractional exhaled nitric oxide, and blood eosinophil counts have emerged as
      predictive and pharmacodynamic biomarkers that may enrich for clinical benefit in
      clinical studies of biologic therapies targeting interleukin-13, interleukin-5,
      and immunoglobulin E. Because airway inflammation and associated biomarkers are
      continuously distributed across the population of patients with asthma, future
      efforts should be directed at identifying clinically relevant biomarker cutoffs
      to target these and other novel therapeutics to the most appropriate patient
      populations. 

PMID- 24313775
TI  - Biomarkers that predict and guide therapy for exacerbations of chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. COPD
      exacerbations have a major impact on morbidity and mortality. The etiology of
      COPD exacerbations is largely due to viral and bacterial infections in
      combination with underlying inflammation that is typically neutrophilic, although
      it is eosinophilic in 10 to 25% of cases. We review the recent studies that have
      defined novel biological clusters at exacerbation events and consequently
      identified important biomarkers to direct therapy. These biomarkers include C
      reactive protein, procalcitonin, and peripheral blood eosinophil count, which are
      readily available. We are therefore at a point of making personalized antibiotic
      and corticosteroid therapy in COPD exacerbations a reality. Integration of the
      wealth of emerging data to further define the complexity of exacerbations also
      promises to identify new targets and biomarkers to treat COPD exacerbations. 

PMID- 24313776
TI  - Conformational distribution and alpha-helix to beta-sheet transition of human
      amylin fragment dimer.
AB  - Experiments suggested that the fibrillation of the 11-25 fragment (hIAPP(11-25))
      of human islet amyloid polypeptide (hIAPP or amylin) involves the formation of
      transient alpha-helical intermediates, followed by conversion to beta-sheet-rich
      structure. However, atomic details of alpha-helical intermediates and the
      transition mechanism are mostly unknown. We investigated the structural
      properties of the monomer and dimer in atomistic detail by replica exchange
      molecular dynamics (REMD) simulations. Transient alpha-helical monomers and
      dimers were both observed in the REMD trajectories. Our calculated H(alpha)
      chemical shifts based on the monomer REMD run are in agreement with the solution
      state NMR experimental observations. Multiple 300 ns MD simulations at 310 K show
      that alpha-helix-to-beta-sheet transition follows two mechanisms: the first
      involved direct transition of the random coil part of the helical conformation
      into antiparallel beta-sheet, and in the second, the alpha-helical conformation
      unfolded and converted into antiparallel beta-sheet. In both mechanisms, the
      alpha-helix-to-beta-sheet transition occurred via random coil, and the transition
      was accompanied by an increase of interpeptide contacts. In addition, our REMD
      simulations revealed different temperature dependencies of helical and beta
      structures. Comparison with experimental data suggests that the propensity for
      hIAPP(11-25) to form alpha-helices and amyloid structures is concentration- and
      temperature-dependent. 

PMID- 24313779
TI  - How do patients with exacerbated chronic obstructive pulmonary disease experience
      care in the intensive care unit?
AB  - The aim was to gain insight into how patients with advanced chronic obstructive
      pulmonary disease (COPD) experience care in the acute phase. The study has a
      qualitative design with a phenomenological approach. The empirics consist of
      qualitative in-depth interviews with ten patients admitted to the intensive care
      units in two Norwegian hospitals. The interviews were carried out from November
      2009 to June 2011. The data have been analysed through meaning condensation, in
      accordance with Amadeo Giorgi's four-step method. Kari Martinsen's
      phenomenological philosophy of nursing has inspired the study. An essential
      structure of the patients' experiences of care in the intensive care unit by
      acute COPD-exacerbation may be described as: Feelings of being trapped in a life
      threatening situation in which the care system assumes control over their lives.
      This experience is conditioned not only by the medical treatment, but also by the
      entire interaction with the caregivers. The essence of the phenomenon is
      presented through three themes which describe the patient's lived experience:
      preserving the breath of life, vulnerable interactions and opportunities for
      better health. Acute COPD-exacerbation is a traumatic experience and the patients
      become particularly vulnerable when they depend on others for breathing support.
      The phenomenological analysis shows that the patients experience good care during
      breath of life preservation when the care is performed in a way that gives
      patients more insight into their illness and gives new opportunities for the
      future. 

PMID- 24313780
TI  - Mucosal mast cell counts in pediatric eosinophilic gastrointestinal disease.

PMID- 24313781
TI  - Siblings caring for and about pediatric palliative care patients.
AB  - BACKGROUND: The experiences of young people who have siblings with life-limiting
      illnesses are not well understood. AIM: The study proposed to identify the
      concerns of siblings of pediatric palliative care (PPC) patients. DESIGN AND
      MEASUREMENT: Semistructured interviews were administered to participants and
      analyzed using qualitative inductive thematic analysis. SETTING AND PARTICIPANTS:
      Study subjects were 18 siblings of PPC patients aged 9 to 22 living in the
      Auckland area. RESULTS: The siblings of PPC patients held concerns about their
      siblings' impending death and desires to be involved in their lives and care.
      CONCLUSIONS: Siblings may benefit from opportunities to be involved in
      conversations about mortality and the care of their ill sibling. They are able to
      express their concerns and help provide care to PPC patients.

PMID- 24313782
TI  - Symptom burden, depression, and suicidality in Chinese elderly patients suffering
      from advanced cancer.

PMID- 24313783
TI  - End-of-life care: lifting the rock.

PMID- 24313777
TI  - TGF-beta activation and function in immunity.
AB  - The cytokine TGF-beta plays an integral role in regulating immune responses. TGF
      beta has pleiotropic effects on adaptive immunity, especially in the regulation
      of effector and regulatory CD4(+) T cell responses. Many immune and nonimmune
      cells can produce TGF-beta, but it is always produced as an inactive complex that
      must be activated to exert functional effects. Thus, activation of latent TGF
      beta provides a crucial layer of regulation that controls TGF-beta function. In
      this review, we highlight some of the important functional roles for TGF-beta in
      immunity, focusing on its context-specific roles in either dampening or promoting
      T cell responses. We also describe how activation of TGF-beta controls its
      function in the immune system, with a focus on the key roles for members of the
      integrin family in this process. 

PMID- 24313784
TI  - Nontyphoidal salmonella infection in children with acute gastroenteritis:
      prevalence, serotypes, and antimicrobial resistance in Shanghai, China.
AB  - Information about nontyphoidal Salmonella (NTS) infection in children is limited
      in mainland China. The objective of this study was to investigate the prevalence,
      serotypes, and antibiotic resistance patterns of NTS infection in children in
      Shanghai. All cases with probable bacterial diarrhea were enrolled from the
      enteric clinic of a tertiary pediatric hospital between July 2010 and December
      2011. Salmonella isolation, serotyping, and antimicrobial susceptibility testing
      were conducted by the microbiological laboratory. NTS were recovered from 316
      (17.2%) of 1833 cases with isolation rate exceeding Campylobacter (7.1%) and
      Shigella (5.7%). NTS infection was prevalent year-round with a seasonal peak
      during summer and autumn. The median age of children with NTS gastroenteritis was
      18 months. Fever and blood-in-stool were reported in 52.5% and 42.7% of cases,
      respectively. Salmonella Enteritidis (38.9%) and Salmonella Typhimurium (29.7%)
      were the most common serovars. Antimicrobial susceptibility showed 60.5% of
      isolates resistant to >=1 clinically important antibiotics. Resistance to
      ciprofloxacin and the third-generation cephalosporins was detected in 5.5% and
      7.1%-11.7% of isolates, respectively. NTS is a major enteropathogen responsible
      for bacterial gastroenteritis in children in Shanghai. Resistance to the current
      first-line antibiotics is of concern. Ongoing surveillance for NTS infection and
      antibiotic resistance is needed to control this pathogen in Shanghai.

PMID- 24313785
TI  - Interactions of O157 and non-O157 Shiga toxin-producing Escherichia coli (STEC)
      recovered from bovine hide and carcass with human cells and abiotic surfaces.
AB  - Different structures related to biofilm formation by Shiga toxin-producing
      Escherichia coli (STEC), particularly O157 strains, have been described, but
      there are few data regarding their involvement in non-O157 strains. The aim of
      this study was to determine the ability of 14 O157 and 8 non-O157 strains
      isolated from bovine hide and carcass to interact with biotic and abiotic
      surfaces and also to evaluate the role of different adhesins. Biofilm formation
      assays showed that four O157 and two non-O157 strains were able to adhere to
      glass, and that only one O157 strain adhered to polystyrene. Reverse
      transcriptase-polymerase chain reaction was carried out using biofilm-forming
      strains to determine the expression of antigen 43 (Ag43), curli, type 1 fimbriae,
      STEC autotransporter contributing to biofilm formation (Sab), calcium-binding
      antigen 43 homologue (Cah), and autotransporter protein of enterohemorrhagic E.
      coli (EhaA). Most of these structures were expressed under biofilm conditions.
      However, the lack of Ag43 in one non-O157 strain, as well as Cah and EhaA in two
      O157 strains, suggests that other adhesins are involved in biofilm formation in
      these strains. Despite the fact that adherence to HeLa cells was detected in 20
      strains (91%), it was not possible to correlate biofilm formation with adherence
      patterns. Invasiveness in T84 and Caco-2 cells was observed in four and three
      O157 strains, respectively. Altogether, we showed that there are different sets
      of genes involved in the interactions of STEC with biotic and abiotic surfaces.
      Interestingly, one O157 strain that was able to form biofilm on both glass and
      polystyrene also adhered to and invaded human cells, indicating an important
      route for its persistence in the environment and interaction with the host.
      Additionally, the ability of non-O157 strains not carrying the LEE pathogenicity
      island to form biofilm highlights an industrial and health problem that cannot be
      neglected.

PMID- 24313787
TI  - Triple helix formation in amphiphilic discotics: demystifying solvent effects in
      supramolecular self-assembly.
AB  - A set of chiral, amphiphilic, self-assembling discotic molecules based on the
      3,3'-bis(acylamino)-2,2'-bipyridine-substituted benzene-1,3,5-tricarboxamide
      motif (BiPy-BTA) was prepared. Amphiphilicity was induced into the discotic
      molecules by an asymmetrical distribution of alkyl and oligo(ethylene oxide)
      groups in the periphery of the molecules. Small-angle X-ray scattering, cryogenic
      transmission electron microscopy, and circular dichroism spectroscopy
      measurements were performed on the discotic amphiphiles in mixtures of water and
      alcohol at temperatures between 0  degrees C an 90  degrees C. The combined
      results show that these amphiphilic discotic molecules self-assemble into
      supramolecular fibers consisting of either one or three discotic molecules in the
      fiber cross-section and that the presence of water induces the bundling of the
      supramolecular fibers. The rich phase behavior observed for these molecules
      proves to be intimately connected to the mixing thermodynamics of the water
      alcohol mixtures. 

PMID- 24313786
TI  - A large outbreak of salmonellosis associated with sandwiches contaminated with
      multiple bacterial pathogens purchased via an online shopping service.
AB  - Food sold over the internet is an emerging business that also presents a concern
      with regard to food safety. A nationwide foodborne disease outbreak associated
      with sandwiches purchased from an online shop in July 2010 is reported. Consumers
      were telephone interviewed with a structured questionnaire and specimens were
      collected for etiological examination. A total of 886 consumers were successfully
      contacted and completed the questionnaires; 36.6% had become ill, with a median
      incubation period of 18 h (range, 6-66 h). The major symptoms included diarrhea
      (89.2%), abdominal pain (69.8%), fever (47.5%), headache (32.7%), and vomiting
      (17.3%). Microbiological laboratories isolated Salmonella enterica serovar
      Enteritidis, Salmonella Virchow, Staphylococcus aureus, Bacillus cereus, and
      enterotoxigenic Escherichia coli from the contaminated sandwiches, Salmonella
      Enteritidis and Salmonella Virchow from the patients, and Salmonella Enteritidis
      and Staphylococcus aureus from food handlers. Pulsed-field gel electrophoresis
      genotyping suggested a common origin of Salmonella bacteria recovered from the
      patients, food, and a food handler. Among the pathogens detected, the symptoms
      and incubation period indicated that Salmonella, likely of egg origin, was the
      probable causative agent of the outbreak. This outbreak illustrates the
      importance of meticulous hygiene practices during food preparation and
      temperature control during food shipment and the food safety challenges posed by
      online food-shopping services.

PMID- 24313788
TI  - Sn powder as reducing agents and SnO2 precursors for the synthesis of SnO2
      reduced graphene oxide hybrid nanoparticles.
AB  - A facile approach to prepare SnO2/rGO (reduced graphene oxide) hybrid
      nanoparticles by a direct redox reaction between graphene oxide (GO) and tin
      powder was developed. Since no acid was used, it is an environmentally friendly
      green method. The SnO2/rGO hybrid nanoparticles were characterized by ultraviolet
      visible spectroscopy, Raman spectroscopy, thermogravimetric analysis, X-ray
      diffraction analysis, and X-ray photoelectron spectroscopy. The microstructure of
      the SnO2/rGO was observed with scanning electron microscopy and transmission
      electron microscopy. The tin powder efficiently reduced GO to rGO, and the Sn was
      transformed to SnO2 nanoparticles (~45 nm) that were evenly distributed on the
      rGO sheets. The SnO2/rGO hybrid nanoparticles were then coated on an interdigital
      electrode to fabricate a humidity sensor, which have an especially good linear
      impedance response from 11% to 85% relative humidity. 

PMID- 24313789
TI  - Loss of visual acuity on the left eye and ipsilateral exophthalmos in a 68-year
      old male patient.

PMID- 24313790
TI  - Family perceptions of insulin pump adverse events in children and adolescents.
AB  - BACKGROUND: Insulin pumps (for continuous subcutaneous insulin infusion [CSII])
      are used widely in type 1 diabetes mellitus. Although there has been considerable
      study of outcomes, there are few recent data on CSII-associated adverse events
      and no data on family perceptions of adverse events and their confidence in
      dealing with them. SUBJECTS AND METHODS: We approached all families of children
      and adolescents <= 19 years of age on CSII attending the diabetes clinic over a
      16-week clinic cycle. Participants completed a retrospective questionnaire
      examining issues over the previous 12 months. Data on pump adverse events as well
      as answers to questions pertaining to education and confidence were collected.
      RESULTS: Our survey received a response rate of 99%, with 235 of the 238 families
      approached participating. In the preceding 12 months, 104 of 230 (45%) had
      reported at least one pump-related adverse event (either mechanical or set
      related), with an associated 52 of 229 (23%) resulting in pump replacement. This
      equated to a minimum incidence density of 53 adverse events/100 person-years.
      Additionally, 18 of 230 (8%) reported a hospital admission or emergency
      department attendance as a consequence. Pump malfunction and infusion set/site
      failures were the most common events reported, with one or more events in 58 of
      104 (56%) and 47 of 104 (45%), respectively. Adverse events, excluding set/site
      failures, were associated with older age (13.1 +/- 3.4 years vs. 11.9 +/- 4
      years; P = 0.02). CONCLUSIONS: This is the first study to look at family
      perceptions of adverse events while using modern CSII. It highlights a high self
      reported rate of CSII-related adverse events, pump replacement, and subsequent
      presentation to the hospital. Potential areas for additional targeted education
      are identified. Further prospective study examining pump adverse event
      characteristics and incidence is warranted.

PMID- 24313791
TI  - Eye-catching eyebrows: training and evaluating humans for periocular image
      verification.
AB  - High-quality periocular images have sufficient variability between people that
      they can be used for automated recognition. However, there are no standards for
      training people to compare periocular images in a forensic context. Potential
      methods for training people to compare eyebrow images are investigated in this
      article. Pairs of images were presented to volunteers who decided whether the
      images showed the same person or different people. A control group with minimal
      instruction and no training responded with 87.6% accuracy. A second group viewed
      100 training pairs before the test and achieved 94.2% accuracy. A third group
      rated specific features in the images and had 0.1% improvement over the second
      group. Experimental results show that actively comparing at least thirty training
      images and receiving immediate feedback improves trainees' performance six to
      seven percent. If a quantitative quality score is needed, a linear combination of
      similarity ratings on different features may be used. 

PMID- 24313793
TI  - Synthesis, bonding, and reactivity of a cerium(IV) fluoride complex.
AB  - Oxidation of Ce[N(SiMe3)2]3 in the presence of PF6(-) or BF4(-) afforded
      isolation of CeF[N(SiMe3)2]3. Structural and electrochemical characterization
      shows that this compound is in its tetravalent oxidation state and contains a
      terminal fluoride ligand. Spectroscopy and density functional theory have been
      used to characterize the Ce-F bond as ionic, which is reinforced by an initial
      reactivity study that demonstrates the nucleophilicity of the fluoride ligand. 

PMID- 24313792
TI  - A microscopic view of phospholipid insertion into biological membranes.
AB  - Understanding the process of membrane insertion is an essential step in
      developing a detailed mechanism, for example, for peripheral membrane protein
      association and membrane fusion. The highly mobile membrane mimetic (HMMM) has
      been used to accelerate the membrane association and binding of peripheral
      membrane proteins in simulations by increasing the lateral diffusion of
      phospholipid headgroups while retaining an atomistic description of the
      interface. Through a comparative study, we assess the difference in insertion
      rate of a free phospholipid into an HMMM as well as into a conventional
      phospholipid bilayer and develop a detailed mechanistic model of free
      phospholipid insertion into biological membranes. The mechanistic insertion model
      shows that successful irreversible association of the free phospholipid to the
      membrane interface, which results in its insertion, is the rate-limiting step.
      Association is followed by independent, sequential insertion of the acyl tails of
      the free phospholipid into the membrane, with splayed acyl tail intermediates.
      Use of the HMMM is found to replicate the same intermediate insertion states as
      in the full phospholipid bilayer; however, it accelerates overall insertion by
      approximately a factor of 3, with the probability of successful association of
      phospholipid to the membrane being significantly enhanced. 

PMID- 24313794
TI  - A description of cases of severe physical abuse in the elderly and 1-year
      mortality.
AB  - We conducted a case-control study to evaluate severe physical abuse of the
      elderly treated in two Chicago area Level I trauma centers. This report details
      whether physicians are adequately reporting cases of abuse to Adult Protective
      Services (APS), and assesses 1 year. The failure to report two-thirds of the
      cases and the substantially higher risk of death during the first year after
      hospitalization indicates the need for improved identification, reporting, and
      intervention. It is important that clinicians understand the complexity of elder
      abuse in order to better identify suspected victims and report these cases to
      professionals in APS. 

PMID- 24313795
TI  - Assessing the level of elder abuse knowledge preprofessionals possess:
      implications for the further development of university curriculum.
AB  - Elder abuse is a multifaceted problemthat requires interdisciplinary prevention
      and intervention strategies. An important question that arises is whether
      professionals are adequately prepared to address elder abuse in this
      collaborative network. Unfortunately, no studies have been conducted to assess
      the varying levels of knowledge that preprofessionals enrolled in university
      courses possess with regard to elder abuse. To fill this void, this study
      assesses the levels of elder abuse awareness among social work, nursing, health
      professions, and criminal justice students. Specific attention is given to
      determining whether there are differences in the amount of exposure to elder
      abuse literature across the disciplines. The study involves the analysis of
      survey data collected from 202 students enrolled in health and human sciences
      classes at a large university. Results show that none of the preprofessional
      groups, on average, reported knowing enough about elder abuse. Implications for
      future practice and research are provided. 

PMID- 24313797
TI  - Multidisciplinary team legislative language associated with elder abuse
      investigations.
AB  - Professionals from different disciplines providing care and services to persons
      at risk for or victims of elder abuse have formed various multidisciplinary teams
      (MDTs). The purpose of the study was to identify the adult protective services
      related statutory trends in presence of MDT content and to determine the
      association of MDT legislation on the rates of reported, investigated, and
      substantiated domestic elder abuse. Aggregate reports of elder abuse and state
      statutes for 1999 and 2007 were retrieved from 50 states and the District of
      Columbia. Statutes of eight states in 2000 and nine in 2008 included text about
      MDTs. In 2007, investigation rates for those states having MDT text in the
      statutes were significantly higher than those states without. The incidence of
      MDTs in the country is unknown. Legislative text is but one factor associated
      with differences in elder abuse report, investigation, or substantiation rates. 

PMID- 24313798
TI  - Elder abuse and barriers to help seeking in Chennai, India: a qualitative study.
AB  - This qualitative study attempts to understand why older persons abused by their
      family members in India do not seek help. In-depth interviews over three visits
      were conducted with six adults aged 65 years and above who had been physically
      abused by their sons/daughters-in-law. The interviews were transcribed and themes
      identified using a thematic analysis method. The barriers preventing a person
      from seeking help were service-related (accessibility, lack of trust); religious
      (Karma); family (deleterious effects on family, family members' responses to help
      seeking); and individual (socioeconomic dependency, self-blame). The unique
      findings that surfaced were fear of losing one's identity by losing one's family,
      attributing abuse to past sins, and concern over not attaining salvation if one's
      sons did not perform funeral rites. The authors propose a checklist to explore
      and assess the barriers to seeking help. Recommendations for geroprofessionals in
      overcoming barriers include implementing outreach programs and changing the
      misconceptions regarding Karma. 

PMID- 24313796
TI  - Systems development and difficulties in implementing procedures for elder abuse
      prevention among private community general support centers in Japan.
AB  - The present study examines differences in systems development and difficulties in
      implementing procedures for elder abuse prevention in 1,119 private and 606
      public community general support centers under the public long-term care
      insurance program in Japan. The private community general support centers showed
      more difficulty implementing procedures than the public community general support
      centers. Controlling for the type of municipality, progress in systems
      development did not differ between the private and public community general
      support centers. Further research should examine how the characteristics of
      municipal governments are related to systems development in community general
      support centers. 

PMID- 24313799
TI  - A national comparison of spousal abuse in mid- and old age.
AB  - This exploratory study addresses whether there are similar or different risks and
      protective factors associated with spousal abuse among mid-age adults (persons
      aged 45-59) and old-age adults (persons aged 60 and over). The risk and
      protective factors of abuse are compared across these two age groups and situated
      within a life course framework. Cross-sectional data from the 1999 and 2004
      General Social Surveys are merged to address the research questions. Overall, it
      was found that there are as many differences as there are similarities in
      risk/protective factors connected to individual, relationship, and community
      environments. The findings are discussed in terms of program development and
      future research. 

PMID- 24313800
TI  - The influence of left and right hemisphere brain damage on configural and
      featural processing of affective faces.
AB  - The literature about the lateralization of facial emotion perception according to
      valence (positive, negative) is conflicting; investigating the underlying
      processes may shed light on why some studies show right-hemisphere dominance
      across valence and other studies demonstrate hemispheric differences according to
      valence. This is the first clinical study to examine whether the use of
      configural and featural cues underlies hemispheric differences in affective face
      perception. Right brain-damaged (RBD; n = 17), left brain-damaged (LBD; n = 17)
      and healthy control (HC; n = 34) participants completed an affective face
      discrimination task that tested configural processing using whole faces and
      featural processing using partial faces. No group differences in expression
      perception according to valence or processing strategy were found. Across
      emotions, the RBD group was less accurate than the HC group in discriminating
      whole faces, whilst the RBD and LBD groups were less accurate than HCs in
      discriminating partial faces. This suggests that the right hemisphere processes
      facial expressions from configural and featural information, whereas the left
      hemisphere relies more heavily on featural facial information. 

PMID- 24313801
TI  - Computer-guided approach to access the anti-influenza activity of licorice
      constituents.
AB  - Neuraminidase (NA), a key enzyme in viral replication, is the first-line drug
      target to combat influenza. On the basis of a shape-focused virtual screening,
      the roots of Glycyrrhiza glabra (licorice) were identified as plant species with
      an accumulation of constituents that show 3D similarities to known influenza NA
      inhibitors (NAIs). Phytochemical investigation revealed 12 constituents
      identified as (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(8-hydroxy-2,2
      dimethyl-2H-1-benzopyran-6-yl)-2-propen-1-one (1), 3,4-dihydro-8,8-dimethyl-2H,8H
      benzo[1,2-b:3,4-b']dipyran-3-ol (2), biochanin B (3), glabrol (4), glabrone (5),
      hispaglabridin B (6), licoflavone B (7), licorice glycoside B (8), licorice
      glycoside E (9), liquiritigenin (10), liquiritin (11), and prunin (12). Eleven of
      these constituents showed significant influenza virus NA inhibition in a
      chemiluminescence (CL)-based assay. Additional tests, including (i) a cell-based
      cytopathic effect inhibition assay (general antiviral activity), (ii) the
      evaluation of cytotoxicity, (iii) the inhibition of the NA of Clostridium
      perfringens (CL- and fluorescence (FL)-based assay), and (iv) the determination
      of self-fluorescence and quenching, provided further perspective on their anti
      influenza virus potential, revealing possible assay interference problems and
      false-positive results. Compounds 1, 3, 5, and 6 showed antiviral activity, most
      likely caused by the inhibition of NA. Of these, compounds 1, 3, and 6 were
      highly ranked in shape-focused virtual screening. 

PMID- 24313802
TI  - Phenotypic differences in white-tailed deer antlerogenic progenitor cells and
      marrow-derived mesenchymal stromal cells.
AB  - Deer antlers are bony appendages that are annually cast and rapidly regrown in a
      seasonal process coupled to the reproductive cycle. Due to the uniqueness of this
      process among mammals, we reasoned that a fundamental characterization of antler
      progenitor cell behavior may provide insights that could lead to improved
      strategies for promoting bone repair. In this study, we investigated whether
      white-tailed deer antlerogenic progenitor cells (APC) conform to basic criteria
      defining mesenchymal stromal cells (MSC). In addition, we tested the effects of
      the artificial glucocorticoid dexamethasone (DEX) on osteogenic and chondrogenic
      differentiation as well as the degree of apoptosis during the latter. Comparisons
      were made to animal-matched marrow-derived MSC. APC and MSC generated similar
      numbers of colonies. APC cultures expanded less rapidly overall but experienced
      population recovery at later time points. In contrast to MSC, APC did not display
      adipogenic in vitro differentiation capacity. Under osteogenic culture
      conditions, APC and MSC exhibited different patterns of alkaline phosphatase
      activity over time. DEX increased APC alkaline phosphatase activity only
      initially but consistently led to decreased activity in MSC. APC and MSC in
      osteogenic culture underwent different time and DEX-dependent patterns of
      mineralization, yet APC and MSC achieved similar levels of mineral accrual in an
      ectopic ossicle model. During chondrogenic differentiation, APC exhibited high
      levels of apoptosis without a reduction in cell density. DEX decreased
      proteoglycan production and increased apoptosis in chondrogenic APC cultures but
      had the opposite effects in MSC. Our results suggest that APC and MSC
      proliferation and differentiation differ in their dependence on time, factors,
      and milieu. Antler tip APC may be more lineage-restricted
      osteo/chondroprogenitors with distinctly different responses to apoptotic and
      glucocorticoid stimuli. 

PMID- 24313803
TI  - Antifouling and antimicrobial polymer membranes based on bioinspired polydopamine
      and strong hydrogen-bonded poly(N-vinyl pyrrolidone).
AB  - A facile and versatile approach for the preparation of antifouling and
      antimicrobial polymer membranes has been developed on the basis of bioinspired
      polydopamine (PDA) in this work. It is well-known that a tightly adherent PDA
      layer can be generated over a wide range of material surfaces through a simple
      dip-coating process in dopamine aqueous solution. The resulting PDA coating is
      prone to be further surface-tailored and functionalized via secondary treatments
      because of its robust reactivity. Herein, a typical hydrophobic polypropylene
      (PP) porous membrane was first coated with a PDA layer and then further modified
      by poly(N-vinyl pyrrolidone) (PVP) via multiple hydrogen-bonding interactions
      between PVP and PDA. Data of water contact angle measurements showed that
      hydrophilicity and wettability of the membranes were significantly improved after
      introducing PDA and PVP layers. Both permeation fluxes and antifouling properties
      of the modified membranes were enhanced as evaluated in oil/water emulsion
      filtration, protein filtration, and adsorption tests. Furthermore, the modified
      membranes showed remarkable antimicrobial activity after iodine complexation with
      the PVP layer. The PVP layer immobilized on the membrane had satisfying long-term
      stability and durability because of the strong noncovalent forces between PVP and
      PDA coating. The strategy of material surface modification reported here is
      substrate-independent, and applicable to a broad range of materials and
      geometries, which allows effective development of materials with novel functional
      coatings based on the mussel-inspired surface chemistry. 

PMID- 24313804
TI  - IMAGe syndrome: clinical and genetic implications based on investigations in
      three Japanese patients.
AB  - OBJECTIVE: Arboleda et al. have recently shown that IMAGe (intra-uterine growth
      restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital
      abnormalities) syndrome is caused by gain-of-function mutations of maternally
      expressed gene CDKN1C on chromosome 11p15.5. However, there is no other report
      describing clinical findings in patients with molecularly studied IMAGe syndrome.
      Here, we report clinical and molecular findings in Japanese patients. PATIENTS:
      We studied a 46,XX patient aged 8.5 years (case 1) and two 46,XY patients aged
      16.5 and 15.0 years (cases 2 and 3). RESULTS: Clinical studies revealed not only
      IMAGe syndrome-compatible phenotypes in cases 1-3, but also hitherto undescribed
      findings including relative macrocephaly and apparently normal pituitary-gonadal
      endocrine function in cases 1-3, familial glucocorticoid deficiency (FGD)-like
      adrenal phenotype and the history of oligohydramnios in case 2, and
      arachnodactyly in case 3. Sequence analysis of CDKN1C, pyrosequencing-based
      methylation analysis of KvDMR1 and high-density oligonucleotide array comparative
      genome hybridization analysis for chromosome 11p15.5 were performed, showing an
      identical de novo and maternally inherited CDKN1C gain-of-function mutation
      (p.Asp274Asn) in cases 1 and 2, respectively, and no demonstrable abnormality in
      case 3. CONCLUSIONS: The results of cases 1 and 2 with CDKN1C mutation would
      argue the following: [1] relative macrocephaly is consistent with maternal
      expression of CDKN1C in most tissues and biparental expression of CDKN1C in the
      foetal brain; [2] FGD-like phenotype can result from CDKN1C mutation; and [3]
      genital abnormalities may primarily be ascribed to placental dysfunction.
      Furthermore, lack of CDKN1C mutation in case 3 implies genetic heterogeneity in
      IMAGe syndrome.

PMID- 24313805
TI  - Curcumin-mediated oxidative stress resistance in Caenorhabditis elegans is
      modulated by age-1, akt-1, pdk-1, osr-1, unc-43, sek-1, skn-1, sir-2.1, and mev
      1.
AB  - Abstract Curcumin (diferuloylmethane), a pharmacologically active substance
      derived from turmeric, exhibits anti-inflammatory, anticarcinogenic, and
      antioxidant properties. We examined the modulation of oxidative-stress resistance
      and associated regulatory mechanisms by curcumin in a Caenorhabditis elegans
      model. Our results showed that curcumin-treated wild-type C. elegans exhibited
      increased survival during juglone-induced oxidative stress compared with the
      control treatment. In addition, curcumin reduced the levels of intracellular
      reactive oxygen species in C. elegans. Moreover, curcumin induced the expression
      of the gst-4 and hsp-16.2 stress response genes. Lastly, our findings from the
      mechanistic study in this investigation suggest that the antioxidative effect of
      curcumin is mediated via regulation of age-1, akt-1, pdk-1, osr-1, unc-43, sek-1,
      skn-1, sir-2.1, and mev-1. Our study elucidates the diverse modes of action and
      signaling pathways that underlie the antioxidant activity exhibited by curcumin
      in vivo. 

PMID- 24313806
TI  - Native top-down electrospray ionization-mass spectrometry of 158 kDa protein
      complex by high-resolution Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) delivers
      high resolving power, mass measurement accuracy, and the capabilities for
      unambiguously sequencing by a top-down MS approach. Here, we report isotopic
      resolution of a 158 kDa protein complex, tetrameric aldolase with an average
      absolute deviation of 0.36 ppm and an average resolving power of ~520 000 at m/z
      6033 for the 26+ charge state in magnitude mode. Phase correction further
      improves the resolving power and average absolute deviation by 1.3-fold.
      Furthermore, native top-down electron capture dissociation (ECD) enables the
      sequencing of 168 C-terminal amino acid (AA) residues out of 463 total AAs.
      Combining the data from top-down MS of native and denatured aldolase complexes, a
      total of 56% of the total backbone bonds were cleaved. The observation of
      complementary product ion pairs confirms the correctness of the sequence and also
      the accuracy of the mass fitting of the isotopic distribution of the aldolase
      tetramer. Top-down MS of the native protein provides complementary sequence
      information to top-down ECD and collisonally activated dissociation (CAD) MS of
      the denatured protein. Moreover, native top-down ECD of aldolase tetramer reveals
      that ECD fragmentation is not limited only to the flexible regions of protein
      complexes and that regions located on the surface topology are prone to ECD
      cleavage.

PMID- 24313807
TI  - Study of the relationships between IL-23R, IL-17, IL-21 polymorphisms and serum
      level of IL-17, IL-21 with acute graft rejection in iranian liver transplant
      recipients.
AB  - Cytokines are important factors determining the outcome of transplantation. Since
      host ability in cytokine production may be affected by cytokine genes
      polymorphisms, the aim of the present study was to investigate the effect of IL
      17, IL-23R and IL-21 gene polymorphisms in outcome of liver transplantation. A
      total of 200 liver transplant recipients were included in this study. IL-17 -197
      A/G, IL-21+1472 G/T, IL-21 5250 C/T, and IL-23R C/A polymorphisms were evaluated
      by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 in rejected
      and non-rejected groups were determined by ELISA method. The results showed that
      IL-23R AC carriers and C allele were significantly more frequent in patients with
      acute rejection than patients without rejection (p=0.01 and p=0.0005,
      respectively). After gender classification, IL-23R AA and AC carriers were
      significantly more frequent in female patients (p=0.01, p=0.01, respectively) and
      IL-23R AA and AC carriers and A allele were significantly more frequent in male
      patients (p=0.009, p=0.02, p=0.003, respectively). There is a significant
      association between CC genotype and C alleles of IL-23R and AR in the patients
      receiving allograft from living donor (p=0.0003 and p=0.0008, respectively).
      Also, IL-23R AA and AC genotypes and C alleles showed a significant association
      with rejection in patients receiving allograft from cadaver donor (p=0.001,
      p=0.002 and p=0.02). The mentioned results indicate that IL-23R AC carriers and C
      allele have predictive values for acute rejection. AC genotype and C allele of IL
      23R is a genetic risk factor for development of acute rejection. Also, AA and AC
      genotype of IL-23R is a sex dependent genetic risk factor for development of
      acute rejection. But this subject needs to be studied in different population.

PMID- 24313808
TI  - Anaerobic nitroxide-catalyzed oxidation of alcohols using the NO+/NO. redox pair.
AB  - A new method for alcohol oxidation using TEMPO or AZADO in conjunction with
      BF3.OEt2 or LiBF4 as precatalysts and tert-butyl nitrite as a stoichiometric
      oxidant has been developed. The system is based on a NO(+)/NO. pair for nitroxide
      reoxidation under anaerobic conditions. This allows the simple, high-yielding
      conversion of various achiral and chiral alcohols to carbonyl compounds without
      epimerization and no formation of nonvolatile byproducts. 

PMID- 24313809
TI  - Perinatal factors and the risk of atopic dermatitis: a cohort study.
AB  - OBJECTIVE: To analyze the effects of pregnancy and early events in the newborn on
      the risk of subsequent atopic dermatitis (AD) during the first year of life.
      PATIENTS AND METHODS: This is a prospective multicenter cohort study of newborns
      during the first year of life. Newborns identified on random days in three
      obstetrics departments in the area of Bergamo, Lombardy, Northern Italy, were
      eligible. At baseline, the mothers were interviewed by medical staff during their
      stay in hospital after delivery. At 6 and 12 months after delivery, a postal
      questionnaire was sent to the parents. Relative risks were calculated with and
      without adjustment by multiple regression analysis. RESULTS: A total of 1081
      newborns entered the study: 796 (74%) parents answered the 12-month
      questionnaire. Hundred and thirty-eight (17%) reported a diagnosis of AD at 6
      months and 222 (28%) at 12 months. Parental history of AD and/or asthma was
      associated with an increased risk of AD (RR 1.5, 95%CI 1.1-2.0). Birth weight was
      slightly associated with an increased risk of AD: RR 1.04, 95%CI 1.001-1.08
      (continuous variable, increment of 100 grams). No association emerged between
      breast feeding, smoking, and risk of AD. CONCLUSIONS: This study in an Italian
      offspring cohort points to family history of atopic diseases and body weight at
      birth as relevant risk factors. The study was unable to document associations
      with other perinatal factors particularly breast feeding and parental smoking in
      the perinatal period.

PMID- 24313810
TI  - Dynamics of mitochondrial Ca2+ uptake in MICU1-knockdown cells.
AB  - MICU1 (Ca2+ uptake protein 1, mitochondrial) is an important regulator of the MCU
      (Ca2+ uniporter protein, mitochondrial) that has been shown recently to act as a
      gatekeeper of the MCU at low [Ca2+]c (cytosolic [Ca2+]). In the present study we
      have investigated in detail the dynamics of MCU activity after shRNA-knockdown of
      MICU1 and we have found several new interesting properties. In MICU1-knockdown
      cells, the rate of mitochondrial Ca2+ uptake was largely increased at a low
      [Ca2+]c (<2 MUM), but it was decreased at a high [Ca2+]c (>4 MUM). In the 2-4 MUM
      range a mixed behaviour was observed, where mitochondrial Ca2+ uptake started
      earlier in the MICU1-silenced cells, but at a lower rate than in the controls.
      The sensitivity of Ca2+ uptake to Ruthenium Red and Ru360 was similar at both
      high and low [Ca2+]c, indicating that the same Ca2+ pathway was operating in both
      cases. The increased Ca2+-uptake rate observed at a [Ca2+]c below 2 MUM was
      transient and became inhibited during Ca2+ entry. Development of this inhibition
      was slow, requiring 5 min for completion, and was hardly reversible. Therefore
      MICU1 acts both as a MCU gatekeeper at low [Ca2+]c and as a cofactor necessary to
      reach the maximum Ca2+-uptake rate at high [Ca2+]c. Moreover, in the absence of
      MICU1, the MCU becomes sensitive to a slow-developing inhibition that requires
      prolonged increases in [Ca2+]c in the low micromolar range.

PMID- 24313811
TI  - New [ONOO]-type amine bis(phenolate) ytterbium(II) and -(III) complexes:
      synthesis, structure, and catalysis for highly heteroselective polymerization of
      rac-lactide.
AB  - Two divalent ytterbium (Yb(II)) complexes, 1 and 2, supported by new [ONOO]-type
      amine bis(phenolate) ligands L(a,b) were synthesized in good yield by an amine
      elimination reaction of Yb(II)(N(SiMe3)2)2(TMEDA) (TMEDA =
      tetramethylethylenediamine) with one equivalent of the ligand precursor. X-ray
      structural determination showed complexes 1 and 2 both have a monomeric
      structure. Each adopts distorted octahedral coordination geometry around the six
      coordinate Yb(II) ion. Two new trivalent ytterbium (Yb(III)) aryloxide complexes,
      4 and 5, bearing [ONOO]-type amine bis(phenolate) ligands L(c) and L(d) were
      prepared by double-protonation reaction of Yb(C5H5)3THF with one equivalent of
      the ligand precursor, then one equivalent of phenol. Complex 4 has a symmetric
      dimeric structure with a Yb2O2 core bridging through the oxygen atoms of the
      OC6H4-4-CH3 groups. Complex 5 is a THF-solvated monomer. Each six-coordinated
      Yb(III) ion in both complexes adopts a distorted octahedron. All the complexes
      synthesized together with the known Yb(II) complex 3 were evaluated in the ring
      opening polymerization (ROP) of rac-lactide (rac-LA). Complexes 1 and 4 were
      found to be extremely active for controlled ROP of rac-LA, as judged by narrow
      molar mass distributions (Mw/Mn: 1.07-1.16 for complex 1 and 1.07-1.10 for
      complex 4) and experimental molar mass Mn,exp values in good agreement with
      theoretic Mn,calcd values calculated on a single PLA chain produced per metal
      center of initiator. Complex 5 is less controlled. Complexes 1, 4, and 5
      exhibited the same high stereoselectivity to give heterotactic polylactide with a
      Pr (probability of racemic enchainment of monomer units) ranging from 0.97 to
      0.99. Dramatic decreases in activity and stereoselectivity were found for
      complexes 2 (Pr = 0.82) and 3 (Pr = 0.67), indicating the framework of L in the
      unit of [YbL] is crucial for determining activity and stereoselectivity of either
      Yb(II) or Yb(III) complexes. 

PMID- 24313812
TI  - Institutional and structural barriers to HIV testing: elements for a theoretical
      framework.
AB  - Stigma is a barrier to HIV health seeking, but little is known about
      institutional and structural expressions of stigma in HIV testing. This study
      examines evidence of institutional and structural stigma in the HIV testing
      process. A qualitative, grounded theory study was conducted using secondary data
      from a 2011 HIV test site evaluation data in a Midwestern, moderate HIV incidence
      state. Expressions of structural and institutional stigma were found with over
      half of the testing sites and at three stages of the HIV testing visit. Examples
      of structural stigma included social geography, organization, and staff behavior
      at first encounter and reception, and staff behavior when experiencing the actual
      HIV test. Institutional stigma was socially expressed through staff behavior at
      entry/reception and when experiencing the HIV test. The emerging elements
      demonstrate the potential compounding of stigma experiences with deleterious
      effect. Study findings may inform future development of a theoretical framework.
      In practice, findings can guide organizations seeking to reduce HIV testing
      barriers, as they provide a window into how test seekers experience HIV test
      sites at first encounter, entry/reception, and at testing stages; and can
      identify how stigma might be intensified by structural and institutional
      expressions.

PMID- 24313813
TI  - Macrocycle contraction and expansion of a dihydrosapphyrin isomer.
AB  - Cyclization of a pentapyrrane with two terminal beta-linked pyrroles afforded a
      dihydrosapphyrin isomer (1) with the pyrroles linked in a unique beta,alpha
      alpha,beta mode, which was rather reactive, and thus it readily underwent a ring
      contracted rearrangement to a pyrrolyl norrole (2), and succeeding ring expansion
      to a terpyrrole-containing isosmaragdyrin analogue (4). 1, 2, and 4 contain the
      internal ring pathways with a minimum of 17, 15, and 16 atoms, respectively. 1,
      2, and 4 are almost nonfluorescent, whereas the complex of 2 with Zn(2+) shows a
      distinct NIR emission peak at 741 nm. The unprecedented pyrrole transformation
      chemistry by confusion approach is illustrated. 

PMID- 24313814
TI  - Protein composition correlates with the mechanical properties of spider ( Argiope
      trifasciata ) dragline silk.
AB  - We investigated the natural variation in silk composition and mechanical
      performance of the orb-weaving spider Argiope trifasciata at multiple spatial and
      temporal scales in order to assess how protein composition contributes to the
      remarkable material properties of spider dragline silk. Major ampullate silk in
      orb-weaving spiders consists predominantly of two proteins (MaSp1 and MaSp2) with
      divergent amino acid compositions and functionally different microstructures.
      Adjusting the expression of these two proteins therefore provides spiders with a
      simple mechanism to alter the material properties of their silk. We first
      assessed the reliability and precision of the Waters AccQ-Tag amino acid
      composition analysis kit for determining the amino acid composition of small
      quantities of spider silk. We then tested how protein composition varied within
      single draglines, across draglines spun by the same spider on different days, and
      finally between spiders. Then, we correlated chemical composition with the
      material properties of dragline silk. Overall, we found that the chemical
      composition of major ampullate silk was in general homogeneous among individuals
      of the same population. Variation in chemical composition was not detectable
      within silk spun by a single spider on a single day. However, we found that
      variation within a single spider's silk across different days could, in rare
      instances, be greater than variation among individual spiders. Most of the
      variation in silk composition in our investigation resulted from a small number
      of outliers (three out of sixteen individuals) with a recent history of stress,
      suggesting stress affects silk production process in orb web spiders. Based on
      reported sequences for MaSp genes, we developed a gene expression model showing
      the covariation of the most abundant amino acids in major ampullate silk. Our
      gene expression model supports that dragline silk composition was mostly
      determined by the relative abundance of MaSp1 and MaSp2. Finally, we showed that
      silk composition (especially proline content) strongly correlated with some
      measures of mechanical performance, particularly how much fibers shrunk during
      supercontraction as well as their breaking strains. Our findings suggest that
      spiders are able to change the relative expression rates of different MaSp genes
      to produce silk fibers with different chemical compositions, and hence, different
      material properties. 

PMID- 24313815
TI  - 'Oh my god, we're not doing nothing': young people's experiences of spatial
      regulation.
AB  - Social psychologists have become increasingly concerned with examining the ways
      in which social practices are interrelated with their location. Critical
      perspectives have highlighted the traditional lack of attention given to both the
      collective aspects of spatial identities, together with the discursive practices
      that construct the relationships between people and places. In this article, we
      draw together the developing discursive work on place with work on children's
      geographies, in order to examine young people's accounts of spatial regulation.
      Adopting a discursive approach to the analysis of focus group discussion, we
      illustrate a variety of concerns managed in relation to spatial practices by 41
      young people living in a large city in the South of England. Our findings suggest
      that everyday use of public space by young people is constructed at a nexus of
      competing concerns around childhood/adulthood, freedom, and citizenship, and
      illustrate the dynamic nature of place, and its regulation, as a resource for
      constructing identities. 

PMID- 24313816
TI  - Prediction of periodontal disease: modelling and validation in different general
      German populations.
AB  - AIM: To develop models for periodontitis using self-reported questions and to
      validate them externally. METHODS: The Study of Health in Pomerania (SHIP-0) was
      used for model development. Periodontitis was defined according to the
      definitions of the Center for Disease Control and Prevention-American Academy of
      Periodontology, the 5th European Workshop in Periodontology, and Dietrich et al.
      (>=2 teeth with inter-proximal clinical attachment loss of >=4 mm and 6 mm as
      moderate and severe periodontitis) respectively. These models were validated in
      SHIP-Trend and the Fourth German Oral Health Study (DMS IV). RESULTS: Final
      models included age, gender, education, smoking, bleeding on brushing and self
      reported presence of mobile teeth. Concordance-statistics (C-statistics) of the
      final models from SHIP-0 were 0.84, 0.82 and 0.85 for the three definitions
      respectively. Validation in SHIP-Trend revealed C-statistics of 0.82, 0.81 and
      0.82 respectively. As bleeding on brushing and presence of mobile teeth were
      unavailable in DMS IV, reduced models were developed. C-statistics of reduced
      models were 0.82, 0.81 and 0.83 respectively. Validation in DMS IV revealed C
      statistics of 0.72, 0.78 and 0.72 for the three definitions respectively. All p
      values of the goodness-of-fit tests were >0.05. CONCLUSIONS: The models yielded a
      moderate usefulness for prediction of periodontitis.

PMID- 24313817
TI  - Gist of Dr. Katsusaburo Yamagiwa's papers entitled "Experimental study on the
      pathogenesis of epithelial tumors" (I to VI reports).
AB  - The concept of cancer and inflammation has a long history. Virchow's irritation
      theory based on human cancer engendered the essential role of inflammation in
      carcinogenesis. Drs. Yamagiwa and Ichikawa first published a comprehensive paper
      entitled "Experimental study on the pathogenesis of epithelial tumors" (I report)
      in 1915 in German, and went on to publish five more reports (1915-1924) under the
      same title. They succeeded in demonstrating that inflammation is an important
      carcinogenic factor, and the mechanisms are now being investigated by numerous
      scientists all over the world. In order to introduce Yamagiwa's work to modern
      cancer researchers, the essentials of their six reports have been translated into
      English as a short review. Scientists' comments on Yamagiwa's contribution are
      attached by way of introduction. 

PMID- 24313818
TI  - Identifying, by first-principles simulations, Cu[amyloid-beta] species making
      Fenton-type reactions in Alzheimer's disease.
AB  - According to the amyloid cascade hypothesis, amyloid-beta peptides (Abeta) play a
      causative role in Alzheimer's disease (AD), of which oligomeric forms are
      proposed to be the most neurotoxic by provoking oxidative stress. Copper ions
      seem to play an important role as they are bound to Abeta in amyloid plaques, a
      hallmark of AD. Moreover, Cu-Abeta complexes are able to catalyze the production
      of hydrogen peroxide and hydroxyl radicals, and oligomeric Cu-Abeta was reported
      to be more reactive. The flexibility of the unstructured Abeta peptide leads to
      the formation of a multitude of different forms of both Cu(I) and Cu(II)
      complexes. This raised the question of the structure-function relationship. We
      address this question for the biologically relevant Fenton-type reaction.
      Computational models for the Cu-Abeta complex in monomeric and dimeric forms were
      built, and their redox behavior was analyzed together with their reactivity with
      peroxide. A set of 16 configurations of Cu-Abeta was studied and the
      configurations were classified into 3 groups: (A) configurations that evolve into
      a linearly bound and nonreactive Cu(I) coordination; (B) reactive configurations
      without large reorganization between the two Cu redox states; and (C) reactive
      configurations with an open structure in the Cu(I)-Abeta coordination, which have
      high water accessibility to Cu. All the structures that showed high reactivity
      with H2O2 (to form HO(*)) fall into class C. This means that within all the
      possible configurations, only some pools are able to produce efficiently the
      deleterious HO(*), while the other pools are more inert. The characteristics of
      highly reactive configurations consist of a N-Cu(I)-N coordination with an angle
      far from 180 degrees  and high water crowding at the open side. This allows the
      side-on entrance of H2O2 and its cleavage to form a hydroxyl radical.
      Interestingly, the reactive Cu(I)-Abeta states originated mostly from the dimeric
      starting models, in agreement with the higher reactivity of oligomers. Our study
      gives a rationale for the Fenton-type reactivity of Cu-Abeta and how dimeric Cu
      Abeta could lead to a higher reactivity. This opens a new therapeutic angle of
      attack against Cu-Abeta-based reactive oxygen species production. 

PMID- 24313819
TI  - The importance of leadership style and psychosocial work environment to staff
      assessed quality of care: implications for home help services.
AB  - Work in home help services is typically conducted by an assistant nurse or
      nursing aide in the home of an elderly person, and working conditions have been
      described as solitary with a high workload, little influence and lack of peer and
      leader support. Relations between leadership styles, psychosocial work
      environment and a number of positive and negative employee outcomes have been
      established in research, but the outcome in terms of quality of care has been
      addressed to a lesser extent. In the present study, we aimed to focus on working
      conditions in terms of leadership and the employee psychosocial work environment,
      and how these conditions are related to the quality of care. The hypothesis was
      that the relation between a transformational leadership style and quality of care
      is mediated through organisational and peer support, job control and workload. A
      cross-sectional survey design was used and a total of 469 questionnaires were
      distributed (March-April 2012) to assistant nurses in nine Swedish home help
      organisations, including six municipalities and one private organisation,
      representing both rural and urban areas (302 questionnaires were returned,
      yielding a 65% response rate). The results showed that our hypothesis was
      supported and, when indirect effects were also taken into consideration, there
      was no direct effect of leadership style on quality of care. The mediated model
      explained 51% of the variance in quality of care. These results indicate that
      leadership style is important not only to employee outcomes in home help services
      but is also indirectly related to quality of care as assessed by staff members. 

PMID- 24313820
TI  - The effects of cyclic conjugation and bending on the optoelectronic properties of
      paraphenylenes.
AB  - Cycloparaphenylenes (CPPs) have optoelectronic properties that are unique when
      compared to their acyclic oligoparaphenylene counterparts. The synthesis and
      characterization of two bent heptaphenyl-containing macrocycles has been achieved
      in order to probe the effects of bending and cyclic conjugation on the properties
      of the CPPs. The study suggests that both bending and cyclic conjugation play a
      role in the novel properties of the CPPs. 

PMID- 24313821
TI  - Association of CTLA-4 gene polymorphism with end-stage renal disease and renal
      allograft outcome.
AB  - Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is upregulated in effector-T-cells
      after activation that may alter signal transduction and subsequently cytokine
      production. The present study was designed to investigate the impact of CTLA-4+49
      A>G (rs231775), -318 C>T (rs5742909), -658 C>T (rs11571317), -1147 C>T
      (rs16840252), -1661 A>G (rs4553808), +6230 A>G (rs3087243) SNPs, and
      microsatellite (AT)n repeat polymorphism among end-stage renal disease (ESRD),
      acute allograft rejection (AR), and delayed graft function (DGF) cases. In this
      regard, 350 ESRD patients and 350 controls were included. Polymerase chain
      reaction (PCR)-restriction fragment length polymorphism analysis method was used
      for genotyping of CTLA-4 SNPs, while PCR-polyacrylamide gel electrophoresis
      method was adopted for studying CTLA4 (AT)n polymorphism. The mutant genotype GG
      of CTLA-4+49A>G,+6230 A>G, and longer alleles of (AT)n repeats polymorphisms were
      risk associated with ESRD, AR, and DGF cases. The distribution of
      haplotype+49G:+6230G and GCTTGG (constructed by using 6 studied SNPs) showed risk
      association for ESRD, DGF, and AR cases. Further, linkage analysis demonstrated
      strong to moderate linkage disequilibrium in our study populations. The meta
      analysis also revealed risk associations for AR cases against GG genotype of CTLA
      4+49A>G SNP, while CTLA-4 -318C>T polymorphism showed no correlation against TT
      genotype among AR cases. Subsequently, no correlation was established against the
      CTLA-4 -318C>T, -658 C>T, -1147 C>T, and -1661 A>G SNPs in the promoter region.
      Survival analysis revealed risk associations against GG genotype of CTLA-4+49A>G,
      +6230 A>G SNP's with overall survival (OS), and higher hazard for the OS. These
      results suggested that CTLA-4 variants might be involved in susceptibility to
      ESRD, AR, and DGF. 

PMID- 24313822
TI  - Acceptance in the domestic environment: the experience of senior housing for
      lesbian, gay, bisexual, and transgender seniors.
AB  - The social environment impacts the ability of older adults to interact
      successfully with their community and age-in-place. This study asked, for the
      first time, residents of existing Lesbian, Gay, Bisexual, and Transgender (LGBT)
      senior living communities to explain why they chose to live in those communities
      and what, if any, benefit the community afforded them. Focus groups were
      conducted at 3 retirement communities. Analysis found common categories across
      focus groups that explain the phenomenon of LGBT senior housing. Acceptance is
      paramount for LGBT seniors and social networks expanded, contrary to
      socioemotional selectivity theory. Providers are encouraged to develop safe
      spaces for LGBT seniors. 

PMID- 24313823
TI  - Development of a tetraplex PCR assay for CYP2D6 genotyping in degraded DNA
      samples.
AB  - CYP2D6 polymorphism analysis is gaining increasing interest in forensic
      pharmacogenetics. Nevertheless, DNA recovered from forensic samples could be of
      poor quality and not suitable for long polymerase chain reaction required to type
      CYP2D6 gene prior to SNaPshot minisequencing analysis performed to define alleles
      with different enzymatic activity. We developed and validated following the
      guidelines of the Scientific Working Group on DNA Analysis Methods a tetraplex
      PCR yielding four amplicons of 597, 803, 1142, and 1659 bp encompassing the
      entire CYP2D6 gene to analyze eleven SNP positions by SNaPshot minisequencing.
      Concordance, sensitivity, and specificity were assessed. The method, applied to
      thirty-two forensic samples failed to amplify with long PCR, allowed the
      amplification of CYP2D6 gene in 62.5% of degraded samples. The new tetraplex PCR
      appears a suitable method for CYP2D6 analysis in forensic pharmacogenetics.

PMID- 24313824
TI  - Template-assisted GLAD: approach to single and multipatch patchy particles with
      controlled patch shape.
AB  - Template-assisted glancing angle deposition (GLAD) is explored for the
      fabrication of single and multipatch patchy particles with one or more patches of
      controlled but asymmetric shape. The template is used to ensure the formation of
      uniform patchy particles, whereas rotation of the template gives access to a
      large number of asymmetric patch shapes caused by the shadowing effect of the
      templating groove and/or the neighboring particle. Careful analysis with a
      straightforward geometric model reveals the effect of the angle of incidence,
      rotational angle, groove size, and particle size on the patch shape. Initial
      magnetic field assembly results are presented to illustrate the removal of patchy
      particles from their template and accessibility to a large number of patchy
      particles. Two-patch particles with overlapping patches are also accessible by
      means of secondary metal vapor deposition. The connectivity of these two patches
      on each particle and the predictable size of the overlapping section provide
      access to functional patchy particles. The combination of the template-assisted
      GLAD method with rotation of the template and secondary evaporation is
      demonstrated to be a good method for fabricating patchy particles with a variety
      of asymmetric patch shapes, sizes, and multipatches where every particle of a
      batch carries exactly the same patch pattern and thereby provides valuable input
      on experimentally accessible patch shapes for future experimental and
      computational studies of patchy particles. 

PMID- 24313825
TI  - Retinol, beta-carotene, oxidative stress, and metabolic syndrome components in
      obese asthmatic children.

PMID- 24313827
TI  - Nanoliposome-based antibacterial drug delivery.
AB  - Although most bacterial infectious diseases can be treated successfully with the
      remarkable array of antibiotics, the microbial pathogens continue to be one of
      the most critical health challenges worldwide. One of the common efforts in
      addressing this issue lies in improving the existing antibacterial delivery
      systems since inefficient delivery can lead to poor therapeutic outcome of the
      administered drug. Recently, nanoliposomal systems have been widely used as
      promising strategies to overcome these challenges due to their unique set of
      properties. This article tries to briefly summarize the current studies that have
      taken advantage of liposomal nanoparticles as carriers to deliver antibacterial
      agents. The reviewed investigations demonstrate the immense potential of
      liposomal nanoparticles as carriers for antibiotic delivery and highlight the
      latent promise in this class of vehicles for treatment of bacterial infections.
      The future of these promising approaches lies in the development of more
      efficient techniques for preparing liposomal nanoparticles with great potential
      in effective and selective targeting of antibiotics to bacterial cells for
      eradication as well as the highest safety for human host. 

PMID- 24313826
TI  - Comparing label-free quantitative peptidomics approaches to characterize diurnal
      variation of peptides in the rat suprachiasmatic nucleus.
AB  - Mammalian circadian rhythm is maintained by the suprachiasmatic nucleus (SCN) via
      an intricate set of neuropeptides and other signaling molecules. In this work,
      peptidomic analyses from two times of day were examined to characterize variation
      in SCN peptides using three different label-free quantitation approaches:
      spectral count, spectra index and SIEVE. Of the 448 identified peptides, 207
      peptides were analyzed by two label-free methods, spectral count and spectral
      index. There were 24 peptides with significant (adjusted p-value < 0.01)
      differential peptide abundances between daytime and nighttime, including multiple
      peptides derived from secretogranin II, cocaine and amphetamine regulated
      transcript, and proprotein convertase subtilisin/kexin type 1 inhibitor.
      Interestingly, more peptides were analyzable and had significantly different
      abundances between the two time points using the spectral count and spectral
      index methods than with a prior analysis using the SIEVE method with the same
      data. The results of this study reveal the importance of using the appropriate
      data analysis approaches for label-free relative quantitation of peptides. The
      detection of significant changes in so rich a set of neuropeptides reflects the
      dynamic nature of the SCN and the number of influences such as feeding behavior
      on circadian rhythm. Using spectral count and spectral index, peptide level
      changes are correlated to time of day, suggesting their key role in circadian
      function. 

PMID- 24313828
TI  - Accumulation of the sigma-1 receptor is common to neuronal nuclear inclusions in
      various neurodegenerative diseases.
AB  - The sigma-1 receptor (SIGMAR1) is now known to be one of the endoplasmic
      reticulum (ER) chaperones, which participate in the degradation of misfolded
      proteins in cells via the ER-related degradation machinery linked to the
      ubiquitin-proteasome pathway. Mutations of the SIGMAR1 gene are implicated in the
      pathogenesis of familial frontotemporal lobar degeneration and motor neuron
      disease. Involvement of ER dysfunction in the formation of inclusion bodies in
      various neurodegenerative diseases has also become evident. We performed
      immunohistochemical staining to clarify the localization of SIGMAR1 in the brains
      of patients with neurodegenerative disorders, including trans-activation response
      DNA protein 43 (TDP-43) proteinopathy, tauopathy, alpha-synucleinopathy,
      polyglutamine disease and intranuclear inclusion body disease (INIBD). Double
      immunocytofluorescence and Western blot analyses of cultured cells were also
      performed to investigate the role of SIGMAR1 using a specific exportin 1
      inhibitor, leptomycin B and an ER stress inducer, thapsigargin. SIGMAR1 was
      consistently shown to be co-localized with neuronal nuclear inclusions in TDP-43
      proteinopathy, five polyglutamine diseases and INIBD, as well as in intranuclear
      Marinesco bodies in aged normal controls. Cytoplasmic inclusions in neurons and
      glial cells were unreactive for SIGMAR1. In cultured cells, immunocytofluorescent
      study showed that leptomycin B and thapsigargin were shown to sequester SIGMAR1
      within the nucleus, acting together with p62. This finding was also supported by
      immunoblot analysis. These results indicate that SIGMAR1 might shuttle between
      the nucleus and the cytoplasm. Neurodegenerative diseases characterized by
      neuronal nuclear inclusions might utilize the ER-related degradation machinery as
      a common pathway for the degradation of aberrant proteins. 

PMID- 24313829
TI  - Trunk bend and twist coordination is affected by low back pain status during
      running.
AB  - Recent literature has related differences in pelvis-trunk coordination to low
      back pain (LBP) status. In addition, repetitive motions involving bending and
      twisting have been linked to high incidence of LBP. The purpose of this study was
      to examine trunk sagittal motion - axial rotation ('bend and twist') coordination
      during locomotion in three groups of runners classified by LBP status (LBP:
      current low back pain; RES: resolved low back pain and CTR: control group with no
      history of LBP). Trunk kinematic data were collected as running speed was
      systematically increased on a treadmill. Within-segment coordination between
      trunk sagittal and transverse planes of motion (trunk lean and axial rotation,
      respectively) was calculated using continuous relative phase (CRP), and
      coordination variability was defined as the between stride cycle standard
      deviation of CRP (CRPvar). Bend-twist coordination was more in-phase for the LBP
      group than CTR (p = 0.010) regardless of running speed. No differences in CRPvar
      were found between the groups. The results from our coordination (CRP) analysis
      were sensitive to LBP status and suggest that multi-plane interactions of the
      trunk should be considered in the assessment of LBP. This analysis also has
      potential for athletically oriented tasks that involve multi-plane interactions
      of the trunk, particularly ones that contain asymmetric action, such as sweep
      rowing or a shot on goal in field hockey or ice hockey.

PMID- 24313830
TI  - Concurrent chronic lymphocytic leukemia and cutaneous T cell lymphoma: a case
      series.

PMID- 24313831
TI  - Utility values for specific chronic myeloid leukemia chronic phase health states
      from the general public in the United Kingdom.
AB  - This study elicited time trade-off (TTO) and standard gamble (SG) preference
      values associated with four health states corresponding to response levels in
      chronic phase chronic myeloid leukemia (CML) from members of the general public
      in the UK (n = 235). Health states studied were treatment-free remission (TFR),
      complete molecular response (CMR, i.e. undetectable disease on treatment),
      molecular response and reappearance of detectable disease (i.e. relapse from TFR
      to molecular response requiring treatment). TFR was the most preferred health
      state (mean utility of 0.97 [TTO] and 0.87 [SG]) followed by CMR (mean utility of
      0.96 [TTO] and 0.85 [SG]) followed by molecular response (mean utility of 0.94
      [TTO] and 0.80 [SG]) followed by reappearance of detectable disease (mean utility
      of 0.90 [TTO] and 0.72 [SG]). SG values were significantly lower than TTO values
      (p < 0.001). The study demonstrated that different treatment responses may impact
      on the health-related quality of life of patients with chronic phase CML.

PMID- 24313832
TI  - Prognostic significance of additional cytogenetic abnormalities and FLT3
      mutations in acute promyelocytic leukemia.

PMID- 24313833
TI  - Controlling lipid oxidation via a biomimetic iron chelating active packaging
      material.
AB  - Previously, a siderophore-mimetic metal chelating active packaging film was
      developed by grafting poly(hydroxamic acid) (PHA) from the surface of
      polypropylene (PP) films. The objective of the current work was to demonstrate
      the potential applicability of this PP-g-PHA film to control iron-promoted lipid
      oxidation in food emulsions. The iron chelating activity of this film was
      investigated, and the surface chemistry and color intensity of films were also
      analyzed after iron chelation. In comparison to the iron chelating activity in
      the free Fe(3+) solution, the PP-g-PHA film retained approximately 50 and 30% of
      its activity in nitrilotriacetic acid (NTA)/Fe(3+) and citric acid/Fe(3+)
      solutions, respectively (pH 5.0), indicating a strong chelating strength for
      iron. The ability of PP-g-PHA films to control lipid oxidation was demonstrated
      in a model emulsion system (pH 3.0). PP-g-PHA films performed even better than
      ethylenediaminetetraacetic acid (EDTA) in preventing the formation of volatile
      oxidation products. The particle size and zeta potential results of emulsions
      indicated that PP-g-PHA films had no adverse effects on the stability of the
      emulsion system. Attenuated total reflectance Fourier transform infrared
      spectroscopy (ATR-FTIR) analysis suggested a non-migratory nature of the PP-g-PHA
      film surface. These results suggest that such biomimetic, non-migratory metal
      chelating active packaging films have commercial potential in protecting foods
      against iron-promoted lipid oxidation. 

PMID- 24313834
TI  - Embodying imagined contact: facial feedback moderates the intergroup consequences
      of mental simulation.
AB  - Imagined contact is a fruitful strategy of improving intergroup attitudes. There
      are several mechanisms responsible for the effectiveness of such contact. This
      article presents a test of an affective mechanism of imagined contact by applying
      a facial feedback procedure. We used a physical blockade of the zygomaticus major
      muscle, known to constrain people's experience of emotional states. Participants
      imagining intergroup contact expressed more positive attitudes towards an
      outgroup when they could physically mimic a positive affective state by smiling,
      but there was no such effect when embodiment was constrained. The interactive
      effects on attitudes appeared due to greater perception of outgroup warmth. This
      study presents the first attempt to explain the role of embodiment in the
      improvement of intergroup relations. 

PMID- 24313835
TI  - A structure-guided fragment-based approach for the discovery of allosteric
      inhibitors targeting the lipophilic binding site of transcription factor EthR.
AB  - A structure-guided fragment-based approach was used to target the lipophilic
      allosteric binding site of Mycobacterium tuberculosis EthR. This elongated
      channel has many hydrophobic residues lining the binding site, with few
      opportunities for hydrogen bonding. We demonstrate that a fragment-based approach
      involving the inclusion of flexible fragments in the library leads to an
      efficient exploration of chemical space, that fragment binding can lead to an
      extension of the cavity, and that fragments are able to identify hydrogen-bonding
      opportunities in this hydrophobic environment that are not exploited in Nature.
      In the present paper, we report the identification of a 1 MUM affinity ligand
      obtained by structure-guided fragment linking.

PMID- 24313836
TI  - Increased levels of cytokines in cerebrospinal fluid of children with aseptic
      meningitis caused by mumps virus and echovirus 30.
AB  - We measured levels of pro-inflammatory cytokines in the cerebrospinal fluid (CSF)
      of patients with mumps meningitis, enteroviral echovirus 30 meningitis and
      children without central nervous system infection to investigate whether these
      molecules were involved in the pathogenesis of viral meningitis. The CSF was
      obtained from 62 children suspected with meningitis. These patients were
      classified to the mumps meningitis (n = 19), echovirus 30 meningitis (n = 22) and
      non-meningitis (n = 21) groups. The concentrations of interleukin-1 (IL-1),
      interleukin-1 soluble receptor type 2 (IL-1R2), interleukin-8 (IL-8), human
      interferon gamma (IFN-gamma) and human tumour necrosis factor alpha (TNF-alpha)
      were determined by immunoassay. A significant increase was noted in the levels of
      IL-8, TNF-alpha and IL-1R2 in the CSF of both meningitis groups as compared to
      controls. The concentrations of IFN-gamma and IL-1 differed significantly only
      between the mumps group and control. The levels of IL-1, IFN-gamma and TNF-alpha
      were significantly higher in mumps meningitis when compared to the echovirus 30
      group. Of all cytokines examined, only IFN-gamma correlated with pleocytosis (r =
      0.58) in the mumps meningitis group. The increased CSF cytokine levels are
      markers of meningeal inflammation, and each virus may cause a specific profile of
      the cytokine pattern.

PMID- 24313837
TI  - Salivary cortisol and psychological factors in women with chronic and acute oro
      facial pain.
AB  - The aim of this study was to compare the salivary cortisol level, pain intensity
      and psychological factors between patients with chronic and acute oro-facial pain
      (OP) and pain-free subjects. Twenty-seven females with chronic OP (a diagnosis of
      myofascial pain according to the Research Diagnostic Criteria for
      Temporomandibular Disorders with at least 6 months duration), 24 females with
      acute OP (<10 days duration) and 27 pain-free females participated. Morning
      saliva was collected from all participants for analyses of the cortisol level.
      The pain intensity was assessed on a 0-10 numeric rating scale. The participants
      were evaluated by the Symptom Checklist 90-revised for levels of depression and
      somatisation, and the Perceived Stress Scale. The cortisol levels among the three
      patient groups were similar with no significant group differences. The median
      (interquartile range) current pain level did not differ between chronic and acute
      OP and was, respectively, 5 (4) and 5 (3). Patients with chronic OP showed
      significantly higher scores for depression, somatisation and perceived stress
      compared with patients with acute OP (Ps < 0.001), but there were no significant
      differences between acute OP and controls. To conclude, there were no differences
      in cortisol level between groups, despite significant higher levels of
      depression, somatisation and perceived stress in patients with chronic OP. This
      shows that psychological distress has a more important role in chronic than in
      acute OP. However, the relation between pain, adreno-cortical activity and
      psychological distress is complex and warrants further investigation.

PMID- 24313838
TI  - Levodopa/carbidopa intestinal gel infusion in advanced Parkinson's disease: a 7
      year experience.
AB  - BACKGROUND AND PURPOSE: Levodopa/carbidopa intestinal gel (LCIG) infusion is
      nowadays becoming an established therapeutic option for advanced Parkinson's
      disease (PD) patients with fluctuating symptoms unresponsive to conventional oral
      treatment. As the implementation of LCIG therapy is increasing, there is a need
      for safety and efficacy data from current clinical practice. METHODS: All PD
      patients treated with LCIG at our centre over a 7-year period were analysed to
      determine the duration of treatment, retention rate, reasons for discontinuation,
      LCIG efficacy in motor complications, modifications of concomitant therapy and
      adverse events. RESULTS: Of the 59 patients, seven subjects (12%) died of causes
      unrelated to LCIG infusion and 11 patients (19%) discontinued therapy prior to
      the cut-off date. Duodopa improved motor complications and over 90% of patients
      reported an improvement in their quality of life, autonomy and clinical global
      status. The most common adverse events were dislocation and kinking of the
      intestinal tube. CONCLUSIONS: LCIG infusion is effective for the long-term
      treatment of advanced PD patients and exerts a positive and clinically
      significant effect on motor complications with a relatively low dropout rate.

PMID- 24313840
TI  - Early repolarization, acute emotional stress and sudden death.
AB  - We herein report the case of a 36-year-old man who died suddenly after a fight
      with another man. Forensic investigations included unenhanced computed
      tomography, postmortem angiography, autopsy, histology, neuropathology,
      toxicology, and biochemistry and allowed a traumatic cause of death to be
      excluded. An electrocardiogram recorded some years prior to death revealed the
      presence of an early repolarization pattern. Based on the results of all
      investigations, the cause of death was determined to be cardiac arrhythmia and
      cardiac arrest during an emotionally stressful event associated with physical
      assault. Direct third party involvement, however, was excluded, and the manner of
      death was listed as natural. The case was not pursued any further by the public
      prosecutor. 

PMID- 24313839
TI  - Defining binding efficiency and specificity of auxins for SCF(TIR1/AFB)-Aux/IAA
      co-receptor complex formation.
AB  - Structure-activity profiles for the phytohormone auxin have been collected for
      over 70 years, and a number of synthetic auxins are used in agriculture. Auxin
      classification schemes and binding models followed from understanding auxin
      structures. However, all of the data came from whole plant bioassays, meaning the
      output was the integral of many different processes. The discovery of Transport
      Inhibitor-Response 1 (TIR1) and the Auxin F-Box (AFB) proteins as sites of auxin
      perception and the role of auxin as molecular glue in the assembly of co-receptor
      complexes has allowed the development of a definitive quantitative structure
      activity relationship for TIR1 and AFB5. Factorial analysis of binding activities
      offered two uncorrelated factors associated with binding efficiency and binding
      selectivity. The six maximum-likelihood estimators of Efficiency are changes in
      the overlap matrixes, inferring that Efficiency is related to the volume of the
      electronic system. Using the subset of compounds that bound strongly, chemometric
      analyses based on quantum chemical calculations and similarity and self
      similarity indices yielded three classes of Specificity that relate to
      differential binding. Specificity may not be defined by any one specific atom or
      position and is influenced by coulomb matrixes, suggesting that it is driven by
      electrostatic forces. These analyses give the first receptor-specific
      classification of auxins and indicate that AFB5 is the preferred site for a
      number of auxinic herbicides by allowing interactions with analogues having van
      der Waals surfaces larger than that of indole-3-acetic acid. The quality factors
      are also examined in terms of long-standing models for the mechanism of auxin
      binding. 

PMID- 24313841
TI  - Innovative multifunctional silk fibroin and hydrotalcite nanocomposites: a
      synergic effect of the components.
AB  - Novel hybrid functional materials are formed by combining hydrotalcite-like
      compounds and silk fibroin (SF-HTlc) via an environmental friendly aqueous
      process. The nanocomposites can be prepared with different weight ratio of the
      constituting components and preserve the conformational properties of the silk
      protein and the lamellar structure of hydrotalcites. Optical microscopy, scanning
      electron microscopy, and atomic force microscopy analyses show a good dispersion
      degree of the inorganic nanoparticles into the organic silk matrix. A mutual
      benefit on the stability of both organic and inorganic components was observed in
      the nanocomposites. SF-HTlc displayed limited dissolution of hydrotalcite in
      acidic medium, enhanced mechanical properties, and higher protease resistance of
      silk protein. The transparency, flexibility, and acidic environment resistance of
      silk fibroin combined to the protective and reinforcing properties of
      hydrotalcites generate a hybrid material, which is very attractive for
      applications in recently reported silk based opto-electronic and photonics
      technologies. 

PMID- 24313843
TI  - Plant interactions with multiple insect herbivores: from community to genes.
AB  - Every plant is a member of a complex insect community that consists of tens to
      hundreds of species that belong to different trophic levels. The dynamics of this
      community are critically influenced by the plant, which mediates interactions
      between community members that can occur on the plant simultaneously or at
      different times. Herbivory results in changes in the plant's morphological or
      chemical phenotype that affect interactions with subsequently arriving
      herbivores. Changes in the plant's phenotype are mediated by molecular processes
      such as phytohormonal signaling networks and transcriptomic rearrangements that
      are initiated by oral secretions of the herbivore. Processes at different levels
      of biological complexity occur at timescales ranging from minutes to years. In
      this review, we address plant-mediated interactions with multiple species of the
      associated insect community and their effects on community dynamics, and link
      these to the mechanistic effects that multiple attacks have on plant phenotypes. 

PMID- 24313842
TI  - Heterotrimeric G protein-coupled signaling in plants.
AB  - Investigators studying G protein-coupled signaling--often called the best
      understood pathway in the world owing to intense research in medical fields--have
      adopted plants as a new model to explore the plasticity and evolution of G
      signaling. Much research on plant G signaling has not disappointed. Although
      plant cells have most of the core elements found in animal G signaling,
      differences in network architecture and intrinsic properties of plant G protein
      elements make G signaling in plant cells distinct from the animal paradigm. In
      contrast to animal G proteins, plant G proteins are self-activating, and
      therefore regulation of G activation in plants occurs at the deactivation step.
      The self-activating property also means that plant G proteins do not need and
      therefore do not have typical animal G protein-coupled receptors. Targets of
      activated plant G proteins, also known as effectors, are unlike effectors in
      animal cells. The simpler repertoire of G signal elements in Arabidopsis makes G
      signaling easier to manipulate in a multicellular context.

PMID- 24313844
TI  - Genetic engineering and breeding of drought-resistant crops.
AB  - Drought is one of the most important environmental stresses affecting the
      productivity of most field crops. Elucidation of the complex mechanisms
      underlying drought resistance in crops will accelerate the development of new
      varieties with enhanced drought resistance. Here, we provide a brief review on
      the progress in genetic, genomic, and molecular studies of drought resistance in
      major crops. Drought resistance is regulated by numerous small-effect loci and
      hundreds of genes that control various morphological and physiological responses
      to drought. This review focuses on recent studies of genes that have been well
      characterized as affecting drought resistance and genes that have been
      successfully engineered in staple crops. We propose that one significant
      challenge will be to unravel the complex mechanisms of drought resistance in
      crops through more intensive and integrative studies in order to find key
      functional components or machineries that can be used as tools for engineering
      and breeding drought-resistant crops. 

PMID- 24313845
TI  - Male sterility and fertility restoration in crops.
AB  - In plants, male sterility can be caused either by mitochondrial genes with
      coupled nuclear genes or by nuclear genes alone; the resulting conditions are
      known as cytoplasmic male sterility (CMS) and genic male sterility (GMS),
      respectively. CMS and GMS facilitate hybrid seed production for many crops and
      thus allow breeders to harness yield gains associated with hybrid vigor
      (heterosis). In CMS, layers of interaction between mitochondrial and nuclear
      genes control its male specificity, occurrence, and restoration of fertility.
      Environment-sensitive GMS (EGMS) mutants may involve epigenetic control by
      noncoding RNAs and can revert to fertility under different growth conditions,
      making them useful breeding materials in the hybrid seed industry. Here, we
      review recent research on CMS and EGMS systems in crops, summarize general models
      of male sterility and fertility restoration, and discuss the evolutionary
      significance of these reproductive systems. 

PMID- 24313846
TI  - Carboxylation with CO2 via Brook rearrangement: preparation of alpha-hydroxy acid
      derivatives.
AB  - In the presence of CsF, a wide range of alpha-substituted alpha-siloxy silanes
      were carboxylated under a CO2 atmosphere (1 atm) via Brook rearrangement. A
      variety of alpha-substituents including aryl, alkenyl, and alkyl groups were
      tolerated to afford alpha-hydroxy acids in moderate-to-high yields. One-pot
      synthesis from aldehydes using PhMe2SiLi and CO2 was also possible, providing
      alpha-hydroxy acids without the isolation of an alpha-hydroxy silane. 

PMID- 24313848
TI  - Secondary functionalization of allyl-terminated GaP(111)A surfaces via heck cross
      coupling metathesis, hydrosilylation, and electrophilic addition of bromine.
AB  - The functionalization of single crystalline gallium phosphide (GaP) (111)A
      surfaces with allyl groups has been performed using a sequential chlorine
      activation/Grignard reaction process. Increased hydrophobicity following reaction
      of a GaP(111)A surface with C3H5MgCl was observed through water contact angle
      measurements. Infrared spectra of GaP(111)A samples after reaction with C3H5MgCl
      showed the asymmetric C?C and C?C-H modes diagnostic of surface-attached allyl
      groups. The stability of allyl-terminated GaP(111)A surfaces under ambient and
      aqueous conditions was investigated. XP spectra of allyl-terminated GaP(111)A
      highlighted a significant resistance against interfacial oxidation both in air
      and in water relative to the native interface. Electrochemical impedance
      spectroscopy indicated a change in the flat-band potential of allyl-terminated
      GaP(111)A electrodes immersed in water relative to native GaP(111)A surfaces.
      Further, the flat-band potentials for allyl-terminated electrodes were
      insensitive to changes in solution pH. The utility of surface-bound allyl groups
      for covalent secondary functionalization of GaP(111)A interfaces was assessed
      through three separate reactions: Heck cross-coupling metathesis,
      hydrosilylation, and electrophilic addition of bromine reactions. Addition of
      aryl groups across the olefins on allyl-terminated GaP(111)A via Heck cross
      coupling was performed and confirmed through high-resolution F 1s and C 1s XP
      spectra and IR spectra. Control experiments with GaP(111)A surfaces
      functionalized with short alkanes indicated no evidence for metathesis.
      Hydrosilylation reactions were separately performed. Si 2s XP spectra, in
      conjunction with infrared spectra, similarly showed secondary evidence of surface
      functionalization for allyl-terminated GaP(111)A but not for CH3-terminated
      GaP(111)A surfaces. Similar analyses showed electrophilic addition of Br2 across
      the terminal olefin on an allyl-terminated GaP(111)A surface after exposure to
      dilute Br2 solutions in CH2Cl2. The work presented herein establishes a set of
      secondary reaction strategies utilizing allyl-terminated surfaces to modify
      chemically protected GaP surfaces. 

PMID- 24313847
TI  - Expression of TWISTED DWARF1 lacking its in-plane membrane anchor leads to
      increased cell elongation and hypermorphic growth.
AB  - Plant growth is achieved predominantly by cellular elongation, which is thought
      to be controlled on several levels by apoplastic auxin. Auxin export into the
      apoplast is achieved by plasma membrane efflux catalysts of the PIN-FORMED (PIN)
      and ATP-binding cassette protein subfamily B/phosphor-glycoprotein (ABCB/PGP)
      classes; the latter were shown to depend on interaction with the FKBP42, TWISTED
      DWARF1 (TWD1). Here by using a transgenic approach in combination with
      phenotypical, biochemical and cell biological analyses we demonstrate the
      importance of a putative C-terminal in-plane membrane anchor of TWD1 in the
      regulation of ABCB-mediated auxin transport. In contrast with dwarfed twd1 loss
      of-function alleles, TWD1 gain-of-function lines that lack a putative in-plane
      membrane anchor (HA-TWD1-Ct ) show hypermorphic plant architecture, characterized
      by enhanced stem length and leaf surface but reduced shoot branching. Greater
      hypocotyl length is the result of enhanced cell elongation that correlates with
      reduced polar auxin transport capacity for HA-TWD1-Ct . As a consequence, HA-TWD1
      Ct displays higher hypocotyl auxin accumulation, which is shown to result in
      elevated auxin-induced cell elongation rates. Our data highlight the importance
      of C-terminal membrane anchoring for TWD1 action, which is required for specific
      regulation of ABCB-mediated auxin transport. These data support a model in which
      TWD1 controls lateral ABCB1-mediated export into the apoplast, which is required
      for auxin-mediated cell elongation. 

PMID- 24313849
TI  - Volunteering and depressive symptoms among residents in a continuing care
      retirement community.
AB  - This descriptive study examined the relationship between volunteer activities,
      depressive symptoms, and feelings of usefulness among older adults using path
      analysis. Survey data was collected via interview from residents of a continuing
      care retirement community. Neither feelings of usefulness nor volunteering were
      directly associated with depressive symptoms. Volunteering was directly
      associated with feelings of usefulness and indirectly associated with depressive
      symptoms through total physical activity. Age, fear of falling, pain, physical
      activity, and physical resilience explained 31% of the variance in depressive
      symptoms. Engaging in volunteer work may be beneficial for increasing feelings of
      usefulness and indirectly improving depressive symptoms among older adults. 

PMID- 24313850
TI  - Suicide in Italy during a time of economic recession: some recent data related to
      age and gender based on a nationwide register study.
AB  - Previous research reported that economic crises may have important implications
      for increasing suicide rates. We investigated official data on completed suicide
      in Italy during the recent economic crisis as related to age and gender. Data
      were extracted from the Italian Mortality Database. The trend in suicide rates
      from 1980 to 2010 (the most recent year available) was analysed by joinpoint
      regression analysis. Rate ratios were calculated to compare suicide rates before
      and after the present economic crisis. Suicide rates for men 25-64 years of age
      (those involved in the labour force) started to increase in 2008 after a period
      of a statistically significant decrease from 1994 to 2007 and their suicide rate
      was 12% higher in 2010 compared with that in 2006. In contrast, suicide rates
      declined for women of all ages and for men younger than 25 and older than 65
      years of age. After 2007, there was a noticeable increase in suicide rates among
      Italian men involved in the labour force. 

PMID- 24313852
TI  - A contribution to reduce sampling variability in the evaluation of deoxynivalenol
      contamination of organic wheat grain.
AB  - Fusarium head blight caused by different varieties of Fusarium species is one of
      the major serious worldwide diseases found in wheat production. It is therefore
      important to be able to quantify the deoxynivalenol concentration in wheat.
      Unfortunately, in mycotoxin quantification, due to the uneven distribution of
      mycotoxins within the initial lot, it is difficult, or even impossible, to obtain
      a truly representative analytical sample. In previous work we showed that the
      sampling step most responsible for variability was grain sampling. In this paper,
      it is more particularly the step scaling down from a laboratory sample of some
      kilograms to an analytical sample of a few grams that is investigated. The
      naturally contaminated wheat lot was obtained from an organic field located in
      the southeast of France (Rhone-Alpes) from the year 2008-2009 cropping season.
      The deoxynivalenol level was found to be 50.6 +/- 2.3 ng g-1. Deoxynivalenol was
      extracted with a acetonitrile-water mix and quantified by gas chromatography
      electron capture detection (GC-ECD). Three different grain sampling techniques
      were tested to obtain analytical samples: a technique based on manually
      homogenisation and division, a second technique based on the use of a rotating
      shaker and a third on the use of compressed air. Both the rotating shaker and the
      compressed air techniques enabled a homogeneous laboratory sample to be obtained,
      from which representative analytical samples could be taken. Moreover, the
      techniques did away with many repetitions and grinding. This study, therefore,
      contributes to sampling variability reduction in the evaluation of deoxynivalenol
      contamination of organic wheat grain, and then, at a reasonable cost.

PMID- 24313851
TI  - Pediatric hereditary angioedema.
AB  - Hereditary angioedema (HAE) is a lifelong illness characterized by recurrent
      swelling of the skin, intestinal tract, and, ominously, the upper airway. It is
      caused by inadequate activity of the protein C1-inhibitor, with dysfunction in
      the kallikrein/bradykinin pathway underlying the clinical symptoms. In addition
      to the physical symptoms, patients experience significant decrements in
      vocational and school achievement as well as in overall quality of life. Symptoms
      often begin in childhood and occur by age 20 in most patients, but life
      threatening attacks are uncommon in the pediatric population. The availability of
      new therapies has transformed the management of HAE. 

PMID- 24313853
TI  - Pyramidal tract abnormalities in the human fetus and infant with trisomy 18
      syndrome.
AB  - Trisomy 18 or Edwards syndrome is known to exhibit various developmental
      abnormalities in the central nervous system. We report dominant uncrossed
      pyramidal tract in trisomy 18 syndrome, based on the postmortem neuropathologic
      study of eight consecutive autopsied fetuses and infants with trisomy 18 ranging
      in age from 16 to 39 weeks of gestation, including six males and two females,
      along with autopsy cases of a stillborn triploid infant with 69XXX and two
      stillborn infants without chromosomal or neurodevelopmental abnormalities. Five
      out of eight cases with trisomy 18 showed a larger proportion of uncrossed than
      crossed pyramidal tract. All of these cases were male, and the anterior
      corticospinal tract on one side was constantly larger than the contralateral
      lateral corticospinal tract in the spinal cord on both sides, while the pyramidal
      tract was hypoplastic in female cases with trisomy 18 and a case with 69XXX.
      Abnormal pyramidal decussation has been found in cases with posterior fossa
      malformations such as occipital encephaloceles, Dandy-Walker malformation,
      Joubert syndrome and Mobius syndrome, but has not been described in cases with
      trisomy 18. Our data, together with the previous reports describing uncrossed
      aberrant ipsilateral pyramidal tract in patients with congenital mirror movements
      caused by DCC gene mutation in chromosome 18, and hypolasia and hyperplasia of
      the pyramidal tract in X-linked recessive disorders caused by L1CAM and Kal1 gene
      mutations, respectively, suggest a role of trisomy 18 in association with X
      chromosome in the abnormal development of the pyramidal tract. 

PMID- 24313854
TI  - Increased soluble C5b-9 in CSF of neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) and multiple sclerosis (MS) are two of the autoimmune
      inflammatory demyelinating diseases in the central nervous system. Complement is
      thought to have an important role in pathogenesis of these diseases, especially
      in NMO. However, the change of terminal complement complex (TCC, C5b-9) in
      patients with NMO is still unclear. Cerebrospinal fluid (CSF) C3a, C5a, sC5b-9
      were measured by enzyme-linked immunosorbent assay in patients with NMO (n = 26),
      MS (n = 25) and other neurological disease (OND, n = 19). CSF levels of C5a in
      patients with NMO were higher than patients with OND (P = 0.006). Increased CSF
      sC5b-9 were found in the patients with NMO compared with patients with MS (P =
      0.029) and OND (P = 0.0001). CSF sC5b-9 in patients with MS were also higher than
      patients with OND (P = 0.030). Patients with NMO revealed a trend to an increased
      disease disability with increased CSF sC5b-9 during relapse but not in MS (NMO: P
      = 0.006, MS: P = 0.097). CSF levels of sC5b-9 are increased in patients with NMO
      and reflect the activation of complement in NMO. 

PMID- 24313855
TI  - The forensic implications of Turner's syndrome.
AB  - Turner's syndrome, the most common sex chromosome disorder of females, is caused
      by complete or partial loss of one X chromosome and is associated with a wide
      range of internal and external manifestations and increased mortality rates
      (three to nine times the background population). While individuals with Turner's
      syndrome may survive for many decades, premature and unexpected deaths can occur
      that bring decedents to the attention of forensic examiners. Causes of death in
      Turner's syndrome are often linked to underlying cardiovascular conditions such
      as aortic dissection, congenital cardiovascular disease, ischemic heart, and
      cerebrovascular disease, but deaths due to noncardiac causes also occur with
      increased frequency. The latter include epilepsy, diabetes mellitus, chronic
      renal disease, pneumonia, chronic liver disease, and malignancy. Thus, the
      autopsy evaluation of these cases requires careful examination of all major organ
      systems, with the consideration of confirmatory cytogenetic testing. 

PMID- 24313857
TI  - Pacemaker rhythm recorded by a cardiac resynchronization device capable of left
      ventricular sensing.

PMID- 24313856
TI  - The nitric oxide pathway and possible therapeutic options in pre-eclampsia.
AB  - Pre-eclampsia is a serious multisystem disorder with diverse clinical
      manifestations. Although not causal, endothelial dysfunction and reduced nitric
      oxide bioavailability are likely to play an important role in the maternal and
      fetal pathophysiology of this condition. Lack of treatment modalities that can
      target the underlying pathophysiological changes and reverse the endothelial
      dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing
      neonatal morbidity and mortality, and the condition itself is associated with
      short- and longer term maternal morbidity and mortality. Drugs that target
      various components of the nitric oxide-soluble guanylyl cyclase pathway can help
      to increase NO bioavailability. The purpose of this review is to outline the
      current status of clinical research involving these therapeutic modalities in the
      context of pre-eclampsia, with the focus being on the following: nitric oxide
      donors, including organic nitrates and S-nitrosothiols; l-arginine, the
      endogenous precursor of NO; inhibitors of cyclic guanosine 3',5'-monophosphate
      breakdown, including sildenafil; and other novel inhibitors of NO donor
      metabolism. The advantages and limitations of each modality are outlined, and
      scope for development into established therapeutic options for pre-eclampsia is
      explored. 

PMID- 24313858
TI  - The designability of protein switches by chemical rescue of structure: mechanisms
      of inactivation and reactivation.
AB  - The ability to selectively activate function of particular proteins via
      pharmacological agents is a longstanding goal in chemical biology. Recently, we
      reported an approach for designing a de novo allosteric effector site directly
      into the catalytic domain of an enzyme. This approach is distinct from
      traditional chemical rescue of enzymes in that it relies on disruption and
      restoration of structure, rather than active site chemistry, as a means to
      achieve modulate function. However, rationally identifying analogous de novo
      binding sites in other enzymes represents a key challenge for extending this
      approach to introduce allosteric control into other enzymes. Here we show that
      mutation sites leading to protein inactivation via tryptophan-to-glycine
      substitution and allowing (partial) reactivation by the subsequent addition of
      indole are remarkably frequent. Through a suite of methods including a cell-based
      reporter assay, computational structure prediction and energetic analysis,
      fluorescence studies, enzymology, pulse proteolysis, X-ray crystallography, and
      hydrogen-deuterium mass spectrometry, we find that these switchable proteins are
      most commonly modulated indirectly, through control of protein stability.
      Addition of indole in these cases rescues activity not by reverting a discrete
      conformational change, as we had observed in the sole previously reported
      example, but rather rescues activity by restoring protein stability. This
      important finding will dramatically impact the design of future switches and
      sensors built by this approach, since evaluating stability differences associated
      with cavity-forming mutations is a far more tractable task than predicting
      allosteric conformational changes. By analogy to natural signaling systems, the
      insights from this study further raise the exciting prospect of modulating
      stability to design optimal recognition properties into future de novo switches
      and sensors built through chemical rescue of structure. 

PMID- 24313859
TI  - A simple method for the electrophilic cyanation of secondary amines.
AB  - Bleach oxidizes trimethylsilyl cyanide to generate an electrophilic cyanating
      reagent that readily reacts with an amine nucleophile. This oxidative N-cyanation
      reaction allows for the preparation of disubstituted cyanamides from amines
      without using highly toxic cyanogen halides. 

PMID- 24313860
TI  - Trust-region algorithm for the inversion of molecular diffusion NMR data.
AB  - Diffusion NMR experiments are very useful in studying structural and dynamical
      properties of molecules and in sorting out components from mixtures. A number of
      numerical approaches have been developed for the processing of diffusion NMR
      data. In this paper, numerical problems of the direct regularization methods such
      as CONTIN, MaxEnt, and the newly proposed ITAMeD approach are illustrated by
      analyzing simulated and experimental data. It allows us to further develop a new
      method to calculate the distribution of diffusion coefficients. Therefore, we
      present here an iterative regularization method based on the Trust-Region
      Algorithm for the Inversion (TRAIn) of molecular diffusion NMR data. It is
      demonstrated in this paper that our approach overcomes major numerical
      difficulties of the direct regularization methods mentioned above. Besides, this
      method reconstructs more reliable diffusion coefficient distributions, especially
      for real world samples of which the diffusion coefficients are nonsymmetrically
      distributed. 

PMID- 24313861
TI  - Hemodynamic effect of external counterpulsation is a different measure of
      impaired cerebral autoregulation from vasoreactivity to breath-holding.
AB  - BACKGROUND AND PURPOSE: External counterpulsation (ECP) is a novel method to
      increase cerebral blood flow, which may benefit acute ischaemic stroke patients.
      Our aim was to identify whether the hemodynamic effect of ECP is associated with
      cerebral vasoreactivity to breath-holding. METHODS: Thirty-seven recent ischaemic
      stroke patients with large artery steno-occlusive disease were recruited together
      with 20 healthy controls. All underwent ECP treatment and a breath-holding test
      combined with transcranial Doppler monitoring on bilateral middle cerebral
      arteries was performed. The data of the stroke patients were designated as
      ipsilateral or contralateral based on the side of the infarct, whilst the average
      of both sides was used in controls. The cerebral augmentation index (CAI) was
      used to evaluate the augmentation effects of ECP. Cerebral vasoreactivity was
      assessed by using the breath-holding index (BHI). RESULTS: Middle cerebral artery
      mean flow velocities significantly increased in the stroke group after ECP but
      not in controls. BHIs were much smaller in the stroke group than in the controls.
      The CAI did not correlate with the BHI in either the ipsilateral or contralateral
      side of the stroke group or in controls. For stroke patients, BHI was
      significantly lower on the ipsilateral side than the contralateral side, but the
      CAI showed no difference between the two cerebral hemisphere sides. The CAI of
      stroke patients was significantly related to mean blood pressure change on the
      ipsilateral side. CONCLUSION: The dynamic augmentation effects of ECP as measured
      by the CAI were different from the well established vasoreactivity to breath
      holding. The CAI is suggested as a measure of how well the brain accommodates
      blood flow augmentation during ECP.

PMID- 24313863
TI  - Gays, guys, and mchicha mwiba: same-sex relations and subjectivities in Dar es
      Salaam.
AB  - Drawing on 15 months of fieldwork, this article explores ways in which same-sex
      relations are perceived and performed in Dar es Salaam, Tanzania. While several
      different constructions of same-sex sexuality coexist in Dar es Salaam, it is
      common to conceive of same-sex practicing men as falling into two main
      categories. Men belonging to each of these differ with respect to the corporeal,
      gendered, and social positions that are open to them, and typically form dyads
      across the conceptual boundary of difference that runs between them. The article
      speaks to the importance of examining sexuality and gender in particular
      sociocultural settings. 

PMID- 24313862
TI  - Are melanomas averse to cerebellum? Cerebellar metastases in a surgical series.
AB  - OBJECTIVES: To study the propensity of different cancers to metastasize to the
      cerebrum and cerebellum, and to study overall survival (OS) and prognostic
      factors for patients after surgical resection for cerebellar metastases.
      MATERIALS AND METHODS: From a prospectively collected tumor database, all
      patients that underwent a craniotomy for intracranial metastases between 2003 and
      2011 at Oslo University Hospital were included. RESULTS: One hundred and forty
      patients underwent resection for cerebellar metastases. Most common primary tumor
      sites were lung, colon/rectum, and breast in 45%, 19%, and 14%, respectively.
      None were prostate cancers. Melanoma metastases were significantly
      underrepresented, and colorectal cancer metastases significantly overrepresented
      in cerebellum, compared to the overall proportion of cerebellar/supratentorial
      metastases surgically resected (P < 0.05). Thirty-day post-operative mortality
      rate was 4.3%. Median OS was 7.7 months (95% CI 6.0-9.5 months) irrespective of
      post-operative adjuvant therapy. Median OS was 51.8, 8.4, and 3.4 months,
      respectively, for recursive partitioning analysis class 1(n = 11), 2 (n = 78) and
      3 (n = 34). Significant negative prognostic factors were age >=65 years,
      Karnofsky performance score (KPS) <70, extracranial metastases and uncontrolled
      systemic disease. CONCLUSIONS: Melanoma metastases were significantly
      underrepresented in cerebellum, whereas colorectal cancer metastases were
      significantly overrepresented. Surgical mortality and OS after surgical treatment
      of cerebellar metastases were similar to the results of supratentorial
      metastases.

PMID- 24313864
TI  - Potential of microneedle-assisted micro-particle delivery by gene guns: a review.
AB  - CONTEXT: Gene guns have been used to deliver deoxyribonucleic acid (DNA) loaded
      micro-particle and breach the muscle tissue to target cells of interest to
      achieve gene transfection. OBJECTIVE: This article aims to discuss the potential
      of microneedle (MN) assisted micro-particle delivery from gene guns, with a view
      to reducing tissue damage. METHODS: Using a range of sources, the main gene guns
      for micro-particle delivery are reviewed along with the primary features of their
      technology, e.g. their design configurations, the material selection of the micro
      particle, the driving gas type and pressure. Depending on the gene gun system,
      the achieved penetration depths in the skin are discussed as a function of the
      gas pressure, the type of the gene gun system and particle size, velocity and
      density. The concept of MN-assisted micro-particles delivery which consists of
      three stages (namely, acceleration, separation and decoration stage) is
      discussed. In this method, solid MNs are inserted into the skin to penetrate the
      epidermis/dermis layer and create holes for particle injection. Several designs
      of MN array are discussed and the insertion mechanism is explored, as it
      determines the feasibility of the MN-based system for particle transfer. RESULTS:
      This review suggests that one of the problems of gene guns is that they need high
      operating pressures, which may result in direct or indirect tissue/cells damage.
      MNs seem to be a promising method which if combined with the gene guns may reduce
      the operating pressures for these devices and reduce tissue/cell damages.
      CONCLUSIONS: There is sufficient potential for MN-assisted particle delivery
      systems.

PMID- 24313865
TI  - Molecular simulation study of the competitive adsorption of H2O and CO2 in
      zeolite 13X.
AB  - The presence of H2O in postcombustion gas streams is an important technical issue
      for deploying CO2-selective adsorbents. Because of its permanent dipole, H2O can
      interact strongly with materials where the selectivity for CO2 is a consequence
      of its quadrupole interacting with charges in the material. We performed
      molecular simulations to model the adsorption of pure H2O and CO2 as well as
      H2O/CO2 mixtures in 13X, a popular zeolite for CO2 capture processes that is
      commercially available. The simulations show that H2O reduces the capacity of
      these materials for adsorbing CO2 by an order of magnitude and that at the
      partial pressures of H2O relevant for postcombustion capture, 13X will be
      essentially saturated with H2O . 

PMID- 24313867
TI  - An antioxidant bioinspired phenolic polymer for efficient stabilization of
      polyethylene.
AB  - The synthesis, structural characterization and properties of a new bioinspired
      phenolic polymer (polyCAME) produced by oxidative polymerization of caffeic acid
      methyl ester (CAME) with horseradish peroxidase (HRP)-H2O2 is reported as a new
      sustainable stabilizer toward polyethylene (PE) thermal and photo-oxidative
      degradation. PolyCAME exhibits high stability toward decarboxylation and
      oxidative degradation during the thermal processes associated with PE film
      preparation. Characterization of PE films by thermal methods, photo-oxidative
      treatments combined with chemiluminescence, and FTIR spectroscopy and mechanical
      tests indicate a significant effect of polyCAME on PE durability. Data from
      antioxidant capacity tests suggest that the protective effects of polyCAME are
      due to the potent scavenging activity on aggressive OH radicals, the efficient H
      atom donor properties inducing free radical quenching, and the ferric ion
      reducing ability. PolyCAME is thus proposed as a novel easily accessible, eco
      friendly, and biocompatible biomaterial for a sustainable approach to the
      stabilization of PE films in packaging and other applications. 

PMID- 24313866
TI  - Mechanistic insights from reaction of alpha-oxiranyl-aldehydes with
      cyanobacterial aldehyde deformylating oxygenase.
AB  - The biosynthesis of long-chain aliphatic hydrocarbons, which are derived from
      fatty acids, is widespread in Nature. The last step in this pathway involves the
      decarbonylation of fatty aldehydes to the corresponding alkanes or alkenes. In
      cyanobacteria, this is catalyzed by an aldehyde deformylating oxygenase. We have
      investigated the mechanism of this enzyme using substrates bearing an oxirane
      ring adjacent to the aldehyde carbon. The enzyme catalyzed the deformylation of
      these substrates to produce the corresponding oxiranes. Performing the reaction
      in D2O allowed the facial selectivity of proton addition to be examined by (1)H
      NMR spectroscopy. The proton is delivered with equal probability to either face
      of the oxirane ring, indicating the formation of an oxiranyl radical intermediate
      that is free to rotate during the reaction. Unexpectedly, the enzyme also
      catalyzes a side reaction in which oxiranyl-aldehydes undergo tandem
      deformylation to furnish alkanes two carbons shorter. We present evidence that
      this involves the rearrangement of the intermediate oxiranyl radical formed in
      the first step, resulting in aldehyde that is further deformylated in a second
      step. These observations provide support for a radical mechanism for
      deformylation and, furthermore, allow the lifetime of the radical intermediate to
      be estimated based on prior measurements of rate constants for the rearrangement
      of oxiranyl radicals. 

PMID- 24313868
TI  - Health-related quality of life and activities of daily living in 85-year-olds in
      Sweden.
AB  - Few studies have examined health-related quality of life (HRQoL) with respect to
      daily living and health factors for relatively healthy elderly individuals. To
      this end, this study examines 85-year-olds' reported HRQoL in relation to social
      support, perceived health, chronic diseases, healthcare use and instrumental
      activities of daily living (IADL). Data were collected from 360 participants (55%
      response rate) between March 2007 and March 2008 using a postal questionnaire and
      a home visit interview. HRQoL was assessed using the EQ-5D-3L. For the items in
      the EQ-5D-3L, more problems were related to lower HRQoL. Restricted mobility and
      occurrence of pain/discomfort was common. Lower HRQoL was associated with
      increased risk for depression, increased use of medication, increased number of
      chronic diseases and more problems with IADL. Healthcare use and healthcare costs
      were correlated with lower HRQoL. HRQoL is of importance to healthcare providers
      and must be considered together with IADL in the elderly population when planning
      interventions. These should take into account the specific needs and resources of
      the older individuals. 

PMID- 24313869
TI  - Dopamine agonist monotherapy in Parkinson's disease and potential risk factors
      for dyskinesia: a meta-analysis of levodopa-controlled trials.
AB  - BACKGROUND AND PURPOSE: Dopamine agonists (DAs) are generally considered to be
      deprived of the highly dyskinetic effect of levodopa in Parkinson's disease (PD)
      patients. However, the risk for dyskinesia induced by DA monotherapy and the
      contribution of clinically significant factors in the development of this
      disorder have never been systematically assessed. METHODS: A systematic
      literature search was conducted for randomized, levodopa-controlled trials of DAs
      in early PD. A meta-analysis was performed to calculate the combined odds ratio
      (OR) for dyskinesia. Meta-regressions were subsequently performed on dyskinesia
      OR including individually as covariates the effects of mean disease duration,
      treatment duration and DA dose. In an additional analysis the effect of adjunct
      levodopa on the odds for dyskinesia was investigated. RESULTS: DA monotherapy
      resulted in an 87% lower risk for dyskinesia compared with treatment with
      levodopa (OR = 0.13, 95% confidence interval 0.09-0.19, P < 0.001). The risk for
      dyskinesia was independent of the dose of DA, disease duration and treatment
      duration. A dose-related pattern was revealed between adjunct levodopa in the DA
      group and dyskinesia. Nevertheless, the odds for dyskinesia in the DA group were
      constantly lower than in the levodopa group. CONCLUSION: Initial DA treatment
      encompasses a lower risk for dyskinesia even after the unavoidable introduction
      of levodopa that increases the risk for dyskinesia in a dose-related manner. As
      the dose and treatment duration with DAs are factors independent of the risk of
      dyskinesia, monotherapy with DAs in early PD is suggested at doses that ensure
      efficacy and delay the need for levodopa, always following an adequate evaluation
      of the risks DAs can pose in individual patients.

PMID- 24313870
TI  - Mycotoxin co-occurrence in rice, oat flakes and wheat noodles used as staple
      foods in Ecuador.
AB  - The co-occurrence of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2),
      ochratoxin A (OTA), deoxynivalenol (DON), fumonisin B1 (FB1), zearalenone (ZEN),
      and HT-2 and T-2 toxins in the main Ecuadorian staple cereals (rice, oat flakes,
      and yellow and white wheat noodles) was evaluated. A ultra high performance
      liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOFMS) method was
      developed and validated to screen for the presence of these mycotoxins in those
      cereal matrices. Matrix-matched calibration curves were used to compensate for
      ion suppression and extraction losses and the recovery values were in agreement
      with the minimum requirements of Regulation 401/2006/EC (70-110%). For most
      mycotoxins, the LODs obtained allowed detection in compliance with the maximum
      permitted levels set in Regulation EC/2006/1881, with the exception of OTA in all
      cereals and AFB1 in yellow noodles. Extra target analysis of OTA in oat flakes
      and wheat noodles was performed by HPLC with fluorescence detection. High rates
      of contamination were observed in paddy rice (23% DON, 23% FB1, 7% AFB1, 2% AFG1
      and 2% AFG2), white wheat noodles (33% DON and 5% OTA) and oat flakes (17% DON,
      2% OTA and 2% AFB1), whereas the rates of contamination were lower in polished
      rice (2% AFG1 and 4% HT-2 toxin) and yellow noodles (5% DON). Low rates of co
      occurrence of several mycotoxins were observed only for white wheat noodles (5%)
      and paddy rice (7%). White noodles were contaminated with DON and/or OTA, while
      combinations of AFG1, AFB1, DON and FB1 were found in paddy rice. Yellow noodles
      were contaminated with DON only; oat flakes contained DON, OTA or AFB1, and
      polished rice was contaminated with AFG1 and HT-2 toxin.

PMID- 24313871
TI  - The progressive effects of a high-fat diet on erythrocyte osmotic fragility,
      growth performance and serum triglyceride and cholesterol levels in Guinea fowl
      (Numida meleagris) and Muscovy duck (Cairina moschata).
AB  - To investigate the progressive effects of a high-fat diet on erythrocyte osmotic
      fragility, growth performance and serum lipid concentrations in Guinea fowl and
      Muscovy ducks, 36 Guinea fowl and 36 Muscovy ducks were divided into two groups,
      for each species, and fed either a standard (STD = commercial poultry feed) or
      high-fat diet (HFD = commercial poultry feed with 20% palm oil and 2% lard) for
      up to 12 weeks. After 4, 8 and 12 weeks on the diets, six birds from each group
      were euthanized and blood samples collected. Osmotic fragility was assessed by
      measuring the haemoglobin released by erythrocytes placed in serially diluted
      solutions of phosphate-buffered saline, spectrophotometrically. Serum
      triglyceride and cholesterol concentrations were also determined. Fragiligrams
      from erythrocytes from both species of birds on the HFD were not different to
      those on the STD. However, Muscovy duck erythrocytes were more resistant to
      haemolysis compared with Guinea fowl erythrocytes. Final body mass and serum
      triglyceride levels were not significantly different (p > 0.05, anova) between
      the birds in the HFD and STD groups, for both species of birds. In contrast,
      serum cholesterol levels were significantly higher in birds on the HFD compared
      with those on the STD, after 4, 8 and 12 weeks of feeding, for both species of
      birds. Feeding Guinea fowl and Muscovy ducks a high-fat diet for up to 12 weeks
      resulted in hypercholesterolaemia but had no effect on final body mass,
      erythrocyte osmotic fragility or serum triglyceride concentrations in either bird
      species. 

PMID- 24313872
TI  - Co-culture of spleen stromal cells with bone marrow mononuclear cells leads to
      the generation of a novel macrophage subset.
AB  - Macrophages adopt diverse activation states depending on the microenvironment.
      Recently, stromal cells have been demonstrated to be organizers of the
      microenvironment. Here, using splenic stromal cells to mimic the splenic
      microenvironment in vivo, we show that spleen stromal cells can programme bone
      marrow-derived mononuclear cells to differentiate and polarize into a novel
      macrophage subset. These differentiated macrophages (Diff-Mphi) exhibited
      pronounced production of IL-10, IL-6 and TNF-alpha, but diminished the production
      of IL-12 in response to LPS. The generation of Diff-Mphi depended on cell-cell
      contact as well as on soluble factors. Diff-Mphi directly suppressed the antigen
      non-specific (CD3/CD28) CD4(+) T cell proliferative response and induced cell
      death of activated CD4(+) T cells. As for cytokine production in CD4(+) T cells,
      Diff-Mphi promoted IL-10 and IL-17 production, whereas inhibited IL-4 production
      and did not alter IFN-gamma production. Besides, Diff-Mphi also expressed iNOS,
      CD16/CD32, CD54, CD43, CCR7, CD44, PD-L1 and FasL, which might be involved in the
      function of Diff-Mphi. These results suggest that splenic microenvironment may
      physiologically induce a novel type of macrophages differentiation. 

PMID- 24313873
TI  - Moxifloxacin dosing in post-bariatric surgery patients.
AB  - INTRODUCTION: Given the ever increasing number of obese patients and obesity
      related bypass surgery, dosing recommendations in the post-bypass population are
      needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic
      (PD) simulations, we investigated whether adequate moxifloxacin concentrations
      are achieved in this population. METHODS: In this modelling and simulation study
      we used data from a trial on moxifloxacin PK. In this trial, volunteers who had
      previously undergone bariatric surgery (at least 6 months prior to inclusion),
      received two doses (intravenous and oral) of 400 mg moxifloxacin administered on
      two occasions. RESULTS: In contrast to other papers, we found that moxifloxacin
      PK were best described by a three compartmental model using lean body mass (LBM)
      as a predictor for moxifloxacin clearance. Furthermore, we showed that the
      probability of target attainment for bacterial eradication against a hypothetical
      Streptococcus pneumoniae infection is compromised in patients with higher LBM,
      especially when targeting microorganisms with minimum inhibitory concentrations
      (MICs) of 0.5 mg l(-1) or higher (probability of target attainment (PTA)
      approaching zero). When considering the targets for suppression of bacterial
      resistance formation, even at MIC values as low as 0.25 mg l(-1) , standard
      moxifloxacin dosing does not attain adequate levels in this population.
      Furthermore, for patients with a LBM of 78 kg or higher, the probability of
      hitting this target approaches zero. CONCLUSIONS: Throughout our PK-PD simulation
      study, it became apparent that, whenever optimal bacterial resistance suppression
      is deemed necessary, the standard moxifloxacin dosing will not be sufficient.
      Furthermore, our study emphasizes the need for a LBM based individualized dosing
      of moxifloxacin in this patient population.

PMID- 24313875
TI  - Accuracy of identifying juvenile/adult status from third molar development using
      prediction probabilities derived from logistic regression analysis.
AB  - The use of third molars in predicting juvenile/adult status (</>= 18 years) has
      important legal ramifications. Third molar development was assessed using
      Kohler's grading on 268 orthopantomograms of Indian subjects. Logistic regression
      analysis was applied to determine allocation accuracy of juvenile/adult status
      and the level of probability that is "reliable" in predicting juvenile/adult
      status. Allocation accuracies ranged between 75.8% and 78.2% for the sexes
      combined, with minimal male-female differences. Adults were categorized more
      accurately than juveniles, suggesting that Kohler's grading puts Indian juveniles
      at greater risk of unwarranted punishment. In both sexes, juvenile/adult status
      was "reliably" predicted when the probability was >80% using individual third
      molars (excepting the lower right third molar in males); combining upper and
      lower third molars on the left/right sides, "reliable" predictions were possible
      when the probability was >80% and >90% for females and males, respectively.
      Overall, "reliable" juvenile/adult status prediction was achieved in c. 36% of
      subjects.

PMID- 24313874
TI  - Redox regulation in Bacillus subtilis: The bacilliredoxins BrxA(YphP) and
      BrxB(YqiW) function in de-bacillithiolation of S-bacillithiolated OhrR and MetE.
AB  - AIMS: In bacillithiol (BSH)-utilizing organisms, protein S-bacillithiolation
      functions as a redox switch in response to oxidative stress and protects critical
      Cys residues against overoxidation. In Bacillus subtilis, both the redox-sensing
      repressor OhrR and the methionine synthase MetE are redox controlled by S
      bacillithiolation in vivo. Here, we identify pathways of protein de
      bacillithiolation and test the hypothesis that YphP(BrxA) and YqiW(BrxB) act as
      bacilliredoxins (Brx) to remove BSH from OhrR and MetE mixed disulfides. RESULTS:
      We present evidence that the BrxA and BrxB paralogs have de-bacillithiolation
      activity. This Brx activity results from attack of the amino-terminal Cys residue
      in a CGC motif on protein BSH-mixed disulfides. B. subtilis OhrR DNA-binding
      activity is eliminated by S-thiolation on its sole Cys residue. Both the BrxA and
      BrxB bacilliredoxins mediate de-bacillithiolation of OhrR accompanied by the
      transfer of BSH to the amino-terminal cysteine of their CGC active site motif. In
      vitro studies demonstrate that BrxB can restore DNA-binding activity to OhrR
      which is S-bacillithiolated, but not to OhrR that is S-cysteinylated. MetE is
      most strongly S-bacillithiolated at Cys719 in vitro and can be efficiently de
      bacillithiolated by both BrxA and BrxB. INNOVATION AND CONCLUSION: We demonstrate
      that BrxA and BrxB function in the reduction of BSH mixed protein disulfides with
      two natural substrates (MetE, OhrR). These results provide biochemical evidence
      for a new class of bacterial redox-regulatory proteins, the bacilliredoxins,
      which function analogously to glutaredoxins. Bacilliredoxins function in concert
      with other thiol-disulfide oxidoreductases to maintain redox homeostasis in
      response to disulfide stress conditions.

PMID- 24313876
TI  - Preprocedural imaging in patients with transposition of the great arteries
      facilitates placement of cardiac resynchronization therapy leads.
AB  - OBJECTIVE: The purpose of this study is to review a series of patients with
      complex congenital heart disease in whom preprocedural imaging was used to assist
      placement of cardiac resynchronization therapy (CRT) leads. BACKGROUND: CRT may
      be beneficial in patients with a failing systemic ventricle and transposition of
      the great arteries (TGA). However, complex coronary venous anatomy can be
      challenging for placement of CRT leads. METHODS: Between October 2006 and June
      2012, seven patients with either dextro-TGA (d-TGA) or levo-TGA (l-TGA) underwent
      preprocedural imaging prior to placement of CRT leads (three, d-TGA and four, l
      TGA). Three patients underwent cardiac computed tomography (CT) and four
      underwent coronary angiography, which included levophase imaging of the coronary
      sinus (CS) or direct contrast injection of the CS. Where CS anatomy was
      appropriate with drainage into the systemic venous circulation, a transvenous
      approach was planned. In all other cases, the patient was referred for surgical
      placement of epicardial leads. RESULTS: Seven patients were identified with
      either d-TGA or l-TGA who had undergone preprocedural imaging prior to placement
      of CRT leads (three, d-TGA and four, l-TGA). Three patients underwent cardiac CT
      and four underwent coronary angiography, which included levophase imaging of the
      CS or direct contrast injection of the CS. All seven patients had successful CRT
      lead placement guided by preprocedure imaging. Three patients required surgical
      placement whereas four were able to undergo transvenous placement. There were no
      complications. The majority of patients (four of seven) had improvement in New
      York Heart Association class as well as subjective improvement in exercise
      tolerance and energy. The majority of patients also had subjective improvement in
      systemic right ventricular function by echocardiogram and objective improvement
      in fractional area change of the right ventricle. The follow-up period ranged
      from 13 months to 55 months with a mean follow-up of 39 months. CONCLUSIONS:
      Placement of biventricular leads for CRT in patients with l-TGA or d-TGA is
      feasible. Preprocedural imaging of the CS allows for better assessment of its
      anatomy and helps determine procedural approach for CRT placement, thereby
      limiting unnecessary procedures. In the majority of patients, there was
      subjective improvement in functional status and right ventricular function; in
      addition, there was objective improvement in echocardiographic parameters of
      right ventricular function after CRT placement.

PMID- 24313877
TI  - Genetic assessment of familial and early-onset Parkinson's disease in a Greek
      population.
AB  - BACKGROUND AND PURPOSE: Although the first mutation associated with Parkinson's
      disease (PD) was identified several years ago in the alpha-synuclein (SNCA) gene
      in families of Greek and Italian ancestry, a more systematic study of this and
      other known PD mutations has not been performed in the Greek population. METHODS:
      A genetic analysis in 111 familial or sporadic with early-onset (<=50 years, EO)
      PD patients was performed for the presence of the A53T SNCA mutation. In separate
      subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1
      and DJ-1 genes were searched for. Additionally, a subgroup of familial cases was
      analysed for mutations in the glucocerebrosidase (GBA) gene. RESULTS: In total,
      five patients (4.5% of our whole population) were identified with the A53T SNCA
      mutation, two with a heterozygote dosage mutation and one with a heterozygote
      point mutation in the Parkin gene, and seven patients (10.3% of our familial
      cohort) with GBA gene mutations. CONCLUSIONS: The A53T mutation in the SNCA gene,
      although uncommon, does represent a cause of PD in the Greek population,
      especially of familial EOPD with autosomal dominant inheritance. GBA mutations in
      the familial cohort tested here were as common as in a cohort of sporadic cases
      previously examined from the same centres. For the remainder of the genes,
      genetic defects that could definitively account for the disease were not
      identified. These results suggest that further Mendelian traits that lead to PD
      in the Greek population remain to be identified.

PMID- 24313878
TI  - Predicting young adult outcome among more and less cognitively able individuals
      with autism spectrum disorders.
AB  - BACKGROUND: The range of outcomes for young adults with Autism Spectrum Disorders
      (ASD) and the early childhood factors associated with this diversity have
      implications for clinicians and scientists. METHODS: This prospective study
      provided a unique opportunity to predict outcome 17 years later for a relatively
      large sample of children diagnosed with ASD at 2 years old. Diagnostic and
      psychometric instruments were administered between 2 and 19 with data from 2, 3,
      and 19 included in this study. Clinicians administered tests without knowledge of
      previous assessments whenever possible. Caregivers provided additional
      information through questionnaires. RESULTS: Significant intellectual
      disabilities at 19 were predicted by age 2 about 85% of the time from VIQ and
      NVIQ scores together, though prediction of young adult outcome for youths with
      average or higher intelligence was more complex. By 19, 9% of participants had
      largely overcome core difficulties associated with ASD and no longer retained a
      diagnosis. These youths with Very Positive Outcomes were more likely to have
      participated in treatment and had a greater reduction in repetitive behaviors
      between age 2 and 3 compared to other Cognitively Able youths (VIQ >=70) with
      ASD. Very Positive Outcome youths did not differ phenotypically from Cognitively
      Able ASD individuals at 2 but both groups differed from Cognitively Less Able
      individuals (VIQ <70). CONCLUSION: Those most at risk for intellectual
      disabilities and ASD can be reliably identified at an early age to receive
      comprehensive treatment. Findings also suggest that some cognitively able
      children with ASD who participate in early intervention have very positive
      outcomes, although replication with randomized, larger samples is needed. In
      order to improve understanding of very positive outcomes in ASD, future research
      will need to identify how variations in child characteristics and environmental
      factors contribute to the nature and timing of growth across individuals and
      areas of development.

PMID- 24313879
TI  - Quantifying the contribution of ambient and indoor-generated fine particles to
      indoor air in residential environments.
AB  - Indoor fine particles (FPs) are a combination of ambient particles that have
      infiltrated indoors, and particles that have been generated indoors from
      activities such as cooking. The objective of this paper was to estimate the
      infiltration factor (Finf ) and the ambient/non-ambient components of indoor FPs.
      To do this, continuous measurements were collected indoors and outdoors for seven
      consecutive days in 50 non-smoking homes in Halifax, Nova Scotia in both summer
      and winter using DustTrak (TSI Inc) photometers. Additionally, indoor and outdoor
      gravimetric measurements were made for each 24-h period in each home, using
      Harvard impactors (HI). A computerized algorithm was developed to remove (censor)
      peaks due to indoor sources. The censored indoor/outdoor ratio was then used to
      estimate daily Finfs and to determine the ambient and non-ambient components of
      total indoor concentrations. Finf estimates in Halifax (daily summer median =
      0.80; daily winter median = 0.55) were higher than have been reported in other
      parts of Canada. In both winter and summer, the majority of FP was of ambient
      origin (daily winter median = 59%; daily summer median = 84%). Predictors of the
      non-ambient component included various cooking variables, combustion sources,
      relative humidity, and factors influencing ventilation. This work highlights the
      fact that regional factors can influence the contribution of ambient particles to
      indoor residential concentrations. PRACTICAL IMPLICATIONS: Ambient and non
      ambient particles have different risk management approaches, composition, and
      likely toxicity. Therefore, a better understanding of their contribution to the
      indoor environment is important to manage the health risks associated with fine
      particles (FPs) effectively. As well, a better understanding of the factors Finf
      can help improve exposure assessment and contribute to reduced exposure
      misclassification in epidemiologic studies.

PMID- 24313880
TI  - Association of uric acid and carotid artery disease in patients with ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Some previous studies reported an independent association
      between uric acid and coronary artery disease, while little is known on the
      association among uric acid and carotid artery disease (CAD). To address this
      issue, we investigated the association between CAD and higher uric acid level
      because of the well-known importance of the carotid artery pathologies for
      ischemic stroke. METHODS: Between 2009 and 2012, we conducted a study among 406
      consecutive first-ever ischemic stroke patients to assess the relationship
      between uric acid and carotid artery. A mean intima-media thickness IMT was
      calculated for the wall of the left and right common carotid arteries (CCA) and
      IMT of the bifurcation of the carotid arteries. CAD was assessed by neuroimaging
      techniques in patients with carotid artery stenosis more than 50%. Logistic
      regression models were used to determine the relation among pathological changes
      of the carotid artery and higher uric acid level. RESULTS: In patients with
      hyperuricemia, the frequency of age (>60 years), hypertriglyceridemia, higher apo
      B, renal failure were significantly higher than those with normal uric acid
      level. CAD was more frequent in patients with hyperuricemia than those with
      normal uric acid level (OR, 1.8, 95% CI, 1.1-3.1; P = 0.01). In patients with
      higher uric acid level, the mean of the IMT of the CCA and of the bifurcation of
      the carotid artery were higher than those with normal uric acid level (P = 0.001
      for each). Covariance matrix analysis displayed a strong correlation between CAD
      and age (>60 years) (P < 0.05), sex (P < 0.01), hyperuricemia (P < 0.01),
      hypertension (P < 0.05), and hypercholesterolemia (P < 0.05). In the models of
      regression analysis, a strong association was found among patients with CAD and
      sex, renal failure, hyperuricemia, number of plaques, and size of plaques.
      CONCLUSION: Our study demonstrated that higher uric acid level is strongly
      associated with CAD. Elevated uric acid might be injurious for large cerebral
      arteries with some probable confounding risk factors. Further prospective large
      clinical trials will determine whether lowering uric acid level reduces the
      frequency of CAD and ischemic stroke.

PMID- 24313881
TI  - Changes of tocopherols, tocotrienols, gamma-oryzanol, and gamma-aminobutyric acid
      levels in the germinated brown rice of pigmented and nonpigmented cultivars.
AB  - This study examined the changes of tocopherols (Toc), tocotrienols (T3), gamma
      oryzanol (GO), and gamma-aminobutyric acid (GABA) contents in germinated brown
      rice (GBR) of pigmented and nonpigmented cultivars under different germination
      conditions. Results showed that the Toc and T3 contents in GBR were significantly
      different between treatments in both rice cultivars. The pigmented GBR possessed
      higher total vitamin E, total Toc, total T3, and GO contents than the
      nonpigmented GBR; however, its level of GABA was lower. The order of the three
      highest vitamin E homologues in pigmented and nonpigmented GBR was gamma-T3 >
      gamma-Toc > alpha-Toc and alpha-Toc > gamma-T3 > alpha-T3, respectively; beta
      Toc, beta-T3, delta-Toc, and delta-T3 were present in only small amounts (<=1.0
      mg/kg) in GBR of both cultivars. Although both cultivars showed an increase in
      GABA contents with increasing germination time, the GABA content in nonpigmented
      GBR was higher. 

PMID- 24313882
TI  - Highly efficient and versatile synthesis of lactams and N-heterocycles via
      Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reactions.
AB  - The discovery and development of an efficient and versatile method for the
      synthesis of N-substituted lactams is described. Pyrrolindinones, piperidones,
      and structurally related heterocycles were formed by Al(OTf)3-catalyzed cascade
      cyclization and ionic hydrogenation reactions of corresponding nitrogen
      substituted ketoamides in good yields. 

PMID- 24313883
TI  - Pancreas transplantation: a treatment option for people with diabetes.
AB  - Since the first pancreas transplants in the early 1960s, whole-organ pancreas
      transplantation, either alone or combined with kidney transplantation, has become
      commonplace in many countries around the world. Whole-organ pancreas
      transplantation is available in the UK, with ~200 transplants currently carried
      out per year. Patient survival and pancreas graft outcome rates are now similar
      to other solid organ transplant programmes, with high rates of long-term insulin
      independence. In the present review, we will discuss whole-pancreas
      transplantation as a treatment for diabetes, focusing on indications for
      transplantation, the nature of the procedure performed, graft survival rates and
      the consequences of pancreas transplantation on metabolic variables and the
      progression of diabetes-related complications. 

PMID- 24313884
TI  - Synthesis of zirconia/polyethylene glycol hybrid materials by sol-gel processing
      and connections between structure and release kinetic of indomethacin.
AB  - Controlled and local drug delivery systems of anti-inflammatory agents are
      attracting an increasing attention because of their extended therapeutic effect
      and reduced side effects. In this work, the sol-gel process was used to
      synthesize zirconia/polyethylene glycol (ZrO2/PEG) hybrid materials containing
      indomethacin for controlled drug delivery. Different percentages of PEG were
      introduced in the synthesis to modulate the release kinetic and an exhaustive
      chemical characterization of all samples was performed to detect the relationship
      between their structure and release ability. Fourier transform spectroscopy and
      solid-state NMR show that the Zr-OH groups of the inorganic matrix bond both the
      ethereal oxygen atoms of the polymer and the carboxylic groups of the drug. X-ray
      diffraction analysis ascertains the amorphous nature of those materials. Scanning
      electron microscopy detects the nanostructure and the homogeneous morphology of
      the synthesized materials. The bioactivity was demonstrated by the formation of a
      hydroxyapatite layer on the surface of the samples, after soaking in a simulated
      body fluid. The release kinetics study, performed by HPLC UV-Vis spectroscopy,
      proves that the release ability depends on PEG and the drug amount and also
      demonstrates the indomethacin integrity after the synthetic treatment.

PMID- 24313885
TI  - Long-term efficacy and safety of Anakinra in a patient with liver transplant due
      to Adult onset Still's Disease.

PMID- 24313886
TI  - Structural characterization of a plant photosystem I and NAD(P)H dehydrogenase
      supercomplex.
AB  - Cyclic electron transport (CET) around photosystem I (PSI) plays an important
      role in balancing the ATP/NADPH ratio and the photoprotection of plants. The
      NAD(P)H dehydrogenase complex (NDH) has a key function in one of the CET
      pathways. Current knowledge indicates that, in order to fulfill its role in CET,
      the NDH complex needs to be associated with PSI; however, until now there has
      been no direct structural information about such a supercomplex. Here we present
      structural data obtained for a plant PSI-NDH supercomplex. Electron microscopy
      analysis revealed that in this supercomplex two copies of PSI are attached to one
      NDH complex. A constructed pseudo-atomic model indicates asymmetric binding of
      two PSI complexes to NDH and suggests that the low-abundant Lhca5 and Lhca6
      subunits mediate the binding of one of the PSI complexes to NDH. On the basis of
      our structural data, we propose a model of electron transport in the PSI-NDH
      supercomplex in which the association of PSI to NDH seems to be important for
      efficient trapping of reduced ferredoxin by NDH. 

PMID- 24313888
TI  - Correlation between the plasma characteristics and the surface chemistry of
      plasma-treated polymers through partial least-squares analysis.
AB  - We investigated the effect of various plasma parameters (relative density of
      atomic N and H, plasma temperature, and vibrational temperature) and process
      conditions (pressure and H2/(N2 + H2) ratio) on the chemical composition of
      modified poly(tetrafluoroethylene) (PTFE). The plasma parameters were measured by
      means of near-infrared (NIR) and UV-visible emission spectroscopy with and
      without actinometry. The process conditions of the N2-H2 microwave discharges
      were set at various pressures ranging from 100 to 2000 mTorr and H2/(N2+H2) gas
      mixture ratios between 0 and 0.4. The surface chemical composition of the
      modified polymers was determined by X-ray photoelectron spectroscopy (XPS). A
      mathematical model was constructed using the partial least-squares regression
      algorithm to correlate the plasma information (process condition and plasma
      parameters as determined by emission spectroscopy) with the modified surface
      characteristics. To construct the model, a set of data input variables containing
      process conditions and plasma parameters were generated, as well as a response
      matrix containing the surface composition of the polymer. This model was used to
      predict the composition of PTFE surfaces subjected to N2-H2 plasma treatment.
      Contrary to what is generally accepted in the literature, the present data
      demonstrate that hydrogen is not directly involved in the defluorination of the
      surface but rather produces atomic nitrogen and/or NH radicals that are shown to
      be at the origin of fluorine atom removal from the polymer surface. The results
      show that process conditions alone do not suffice in predicting the surface
      chemical composition and that the plasma characteristics, which cannot be easily
      correlated with these conditions, should be considered. Process optimization and
      control would benefit from plasma diagnostics, particularly infrared emission
      spectroscopy. 

PMID- 24313889
TI  - Anetodermic pilomatricoma in a patient with hypermobility syndrome.

PMID- 24313887
TI  - Seroreactive marker for inflammatory bowel disease and associations with
      antibodies to dietary proteins in bipolar disorder.
AB  - OBJECTIVES: Immune sensitivity to wheat glutens and bovine milk caseins may
      affect a subset of individuals with bipolar disorder. Digested byproducts of
      these foods are exorphins that have the potential to impact brain physiology
      through action at opioid receptors. Inflammation in the gastrointestinal (GI)
      tract might accelerate exposure of food antigens to systemic circulation and help
      explain elevated gluten and casein antibody levels in individuals with bipolar
      disorder. METHODS: We measured a marker of GI inflammation, anti-Saccharomyces
      cerevisiae antibodies (ASCA), in non-psychiatric controls (n = 207), in patients
      with bipolar disorder without a recent onset of psychosis (n = 226), and in
      patients with bipolar disorder with a recent onset of psychosis (n = 38). We
      compared ASCA levels to antibodies against gluten, casein, Epstein-Barr virus
      (EBV), herpes simplex virus 1 (HSV-1), influenza A, influenza B, measles, and
      Toxoplasma gondii. RESULTS: Elevated ASCA conferred a 3.5-4.4-fold increased odds
      ratio of disease association (age-, race-, and gender-corrected multinomial
      logistic regressions, p <= 0.00001) that was independent of type of medication
      received. ASCA correlated with food antibodies in both bipolar disorder groups
      (R(2)  = 0.29-0.59, p <= 0.0005), and with measles and T. gondii immunoglobulin G
      (IgG) in the recent onset psychosis bipolar disorder group (R(2)  = 0.31-0.36, p
      <= 0.004-0.01). CONCLUSIONS: Elevated seropositivity of a GI-related marker and
      its association with antibodies to food-derived proteins and self-reported GI
      symptoms suggest a GI comorbidity in at least a subgroup of individuals with
      bipolar disorder. Marker seroreactivity may also represent part of an overall
      heightened activated immune state inherent to this mood disorder.

PMID- 24313890
TI  - Evidence for the coexistence of interpenetrating permanent and transient networks
      of hydroxypropyl methyl cellulose.
AB  - Dynamic mechanical properties of aqueous solutions of hydroxypropyl methyl
      cellulose (HPMC) were investigated using oscillatory shear measurements. The
      structure was investigated with light scattering. A systematic investigation of
      the frequency dependence of the shear moduli showed that HPMC forms two distinct
      interpenetrating networks. A transient network is formed above about 0.3 wt % by
      reversible cross-linking of the chains. The elastic modulus of this network is
      independent of the temperature, but increases linearly with the concentration. An
      independent permanent network is formed involving a small fraction of the
      polymers and has an elastic modulus that increases with increasing temperature.
      Its elastic modulus is history dependent and evolves slowly with time. The
      transient network collapses at a critical temperature where micro phase
      separation occurs, but the permanent network is not influenced by this
      phenomenon. Light scattering showed that the pore size of the transient network
      is less than 40 nm, while probe diffusion measurements showed that the pore size
      of the permanent network is larger than 1 MUm. 

PMID- 24313891
TI  - Sexual orientation and fear at night: gender differences among sexual minorities
      and heterosexuals.
AB  - Using data from the 2000-2010 General Social Survey, a nationally representative
      sample of 5,086 adults in the United States, the authors examine sexual
      orientation and gender differences in reports of being afraid to walk alone at
      night. Results indicate that sexual minorities are significantly more likely to
      report fear at night than heterosexuals, and women are significantly more likely
      to report such fear than men. Further, our findings suggest that these sexual
      orientation and gender differences are due to sexual minority men being more
      likely than heterosexual men to report fear at night. Thus, the results of this
      study reveal that three groups--heterosexual women, sexual minority women, and
      sexual minority men--do not differ from one another in reporting fear, yet these
      groups are all more likely than heterosexual men to report fear at night. These
      findings give weight to the importance of investigating the intersection of
      sexual orientation and gender in individuals' reports of fear.

PMID- 24313892
TI  - Rapid evolution of larval life history, adult immune function and flight muscles
      in a poleward-moving damselfly.
AB  - Although a growing number of studies have documented the evolution of adult
      dispersal-related traits at the range edge of poleward-expanding species, we know
      little about evolutionary changes in immune function or traits expressed by
      nondispersing larvae. We investigated differentiation in larval (growth and
      development) and adult traits (immune function and flight-related traits) between
      replicated core and edge populations of the poleward-moving damselfly Coenagrion
      scitulum. These traits were measured on individuals reared in a common garden
      experiment at two different food levels, as allocation trade-offs may be easier
      to detect under energy shortage. Edge individuals had a faster larval life
      history (growth and development rates), a higher adult immune function and a
      nearly significant higher relative flight muscle mass. Most of the
      differentiation between core and edge populations remained and edge populations
      had a higher relative flight muscle mass when corrected for latitude-specific
      thermal regimes, and hence could likely be attributed to the range expansion
      process per se. We here for the first time document a higher immune function in
      individuals at the expansion front of a poleward-expanding species and documented
      the rarely investigated evolution of faster life histories during range
      expansion. The rapid multivariate evolution in these ecological relevant traits
      between edge and core populations is expected to translate into changed
      ecological interactions and therefore has the potential to generate novel eco
      evolutionary dynamics at the expansion front. 

PMID- 24313893
TI  - Angiostatic effects of NK cell-derived IFN-gamma counteracted by tumour cell Bcl
      xL expression.
AB  - Anti-apoptotic proteins that block death receptor-mediated apoptosis favour
      tumour evasion of the immune system, leading to enhanced tumour progression.
      However, it is unclear whether blocking the mitochondrial pathway of apoptosis
      will protect tumours from immune cell attack. Here, we report that the anti
      apoptotic protein Bcl-xL , known for its ability to block the mitochondrial
      pathway of apoptosis, exerted tumour-progressive activity in a murine lymphoma
      model. Bcl-xL overexpressing tumours exhibited a more aggressive development than
      control tumours. Surprisingly, Bcl-xL protection of tumours from NK cell-mediated
      attack did not involve protection from NK cell-mediated cytotoxicity. Instead,
      Bcl-xL -blocked apoptosis resulting from hypoxia and/or nutrient loss associated
      with the inhibition of angiogenesis caused by NK cell-secreted IFN-gamma. These
      results support the notion that NK cells may inhibit tumour growth also by
      mechanisms other than direct cytotoxicity. Hence, the present results unravel a
      pathway by which tumours with a block in the mitochondrial pathway of apoptosis
      can evade the immune system. 

PMID- 24313894
TI  - Anticardiolipin antibodies are associated with cognitive dysfunction in stroke
      free individuals.
AB  - BACKGROUND AND PURPOSE: The presence of anticardiolipin antibodies (aCLs) has
      been associated with vascular occlusive events. The role of aCLs as a risk factor
      for stroke has been a matter of debate, and scarce information exists on the
      relationship between aCLs and other cerebral disorders. Reports exist for
      seizures, chorea and subtle cognitive dysfunction. The association between aCLs
      and cognition was further explored and the relationship between aCL titres and
      brain magnetic resonance imaging (MRI) findings was evaluated in a large cohort
      of community-dwelling individuals. METHODS: The study cohort was drawn from the
      Austrian Stroke Prevention Study. A total of 1895 subjects had a complete risk
      factor assessment and measurement of aCL titres in serum. Participants were
      classified as aCL positive if either the immunoglobulin G (IgG) or IgM aCL titres
      were elevated (IgG > 21 U/ml, IgM > 12 U/ml). All subjects were also categorized
      based on the quartile distribution of IgG and IgM isotype titres. All underwent
      cognitive testing by the Mini Mental State Examination (MMSE) and a random sample
      of 947 participants also underwent brain MRI. RESULTS: aCL positive participants
      performed worse on the MMSE. IgG but not IgM isotype titres related to worse
      performance on the MMSE. No significant association existed with vascular brain
      abnormalities including lacunes, cortical infarcts and white matter lesions.
      CONCLUSIONS: These data support the view that in normal elderly persons
      increasing IgG aCL titres relate to global cognitive dysfunction. It is unlikely
      that structural brain lesions are responsible for this finding.

PMID- 24313896
TI  - Aspergillus section Nigri as contributor of fumonisin B(2) contamination in
      maize.
AB  - Fumonisins (FBs), which are carcinogenic mycotoxins, are known to be typically
      produced by several phytopathogenic fungal species belonging to the genus
      Fusarium. F. proliferatum and F. verticillioides, two important pathogens of
      maize worldwide, are the most common species that produce FBs. The main FBs
      produced by these species are FB1, FB2 and FB3. Moreover, recently, fungal
      strains belonging to Aspergillus niger have been also reported to produce FBs (in
      particular, FB2 and FB4). In a survey on maize carried out in Central Italy, 17
      maize kernel samples were collected at harvest and analysed for FB1, FB2 and FB3,
      as well as fungal contamination, with a particular attention to the species
      producing FBs. All 17 samples were contaminated by F. verticillioides and/or F.
      proliferatum at a level ranging from 13% to 100% of kernels. However, 10 out of
      17 samples were also contaminated by Aspergillus section Nigri with a range from
      6% to 68% of kernels. There was a significant inverse logarithmic relationship
      between levels of Fusarium and Aspergillus contamination. All samples were
      contaminated by FBs; FB1 ranged from 0.09 to 30.2 MUg g(-1), whereas FB2 ranged
      from 0.04 to 13.2 MUg g(-1). The ratio of FB2/FB1 contamination in the maize
      samples was evaluated and the highest values occurred in samples contaminated
      with Aspergillus section Nigri. Thirty strains of Aspergillus section Nigri
      isolated from these samples were molecularly identified (based on sequences of
      two housekeeping genes) and analysed for their capability to produce FB2. Among
      the 30 strains isolated, 12 were identified as Aspergillus welwitschiae (syn. A.
      awamori) and 18 as A. tubingensis. FB2 was produced by five out of 12 strains of
      A. welwitschiae within a range of 0.20-5 MUg g(-1). This is the first report
      showing the capability of Aspergillus section Nigri from maize to produce FB2 and
      its possibility to contribute to FB accumulation in kernels.

PMID- 24313897
TI  - Tetrafluorothiophene S,S-dioxide: a perfluorinated building block.
AB  - Tetrafluorothiophene S,S-dioxide, a highly reactive diene and dienophile, has
      been synthesized. A new route to 3,4-difluoro- and tetrafluorothiophene has been
      realized, and the previously unknown 2,3,4-trifluorothiophene has been obtained.
      The reactivity of tetrafluorothiophene S-oxide has been compared with that of the
      S,S-dioxide. 

PMID- 24313898
TI  - Cardiac and proinflammatory markers predict prognosis in cirrhosis.
AB  - BACKGROUND & AIMS: Inflammation and cardiac dysfunction plays an important role
      in the development of complications leading to increased mortality in patients
      with cirrhosis. Novel cardiac markers such as prohormone of ANP (proANP),
      copeptin and high-sensitivity troponin T (hs-TnT) and proinflammatory markers
      including soluble urokinase-type plasminogen activator receptor (suPAR) and high
      sensitive C-reactive protein (hs-CRP) are related to these complications. We
      aimed to investigate if cardiac and proinflammatory markers are related to
      severity of liver disease, cardiac and haemodynamic changes, and long-term
      survival. METHODS: One hundred and ninety-three stable cirrhotic patients (Child
      class: A = 46; B = 97; C = 50) had a full haemodynamic investigation performed
      with measurement of splanchnic and systemic haemodynamics and measurement of
      circulating levels of proBNP, proANP, copeptin, hs-TnT, LBP, IL 6, IL 8, IP 10,
      VEGF, hs-CRP and suPAR. RESULTS: Soluble urokinase-type plasminogen activator
      receptor soluble urokinase-type plasminogen activator receptor, hs-CRP, and hs
      TnT were significantly different throughout the Child classes (P < 0.01; P <
      0.01; P < 0.02). All markers except copeptin correlated with indicators of
      disease severity in cirrhosis; ProANP and suPAR correlated with hepatic venous
      pressure gradient (r = 0.24 and r = 0.34; P < 0.001) and systemic vascular
      resistance (r = -0.24 and r = -0.33; P < 0.001). Cardiac (proANP, hs-TnT; P <
      0.01) and proinflammatory (hs-CRP, suPAR; P < 0.05) markers were associated with
      mortality in a univariate Cox analysis, however, the strongest predictors of
      mortality in a multivariate Cox analysis were hs-TnT, ascites and hepatic venous
      pressure gradient (reg.coeff.: 0.34, P < 0.001; 0.16, P < 0.001; 0.06, P = 0.04).
      CONCLUSION: Markers of cardiac dysfunction and inflammation are significantly
      associated with disease severity, degree of portal hypertension and survival in
      cirrhosis. In particular, hs-TnT and suPAR seem to contain prognostic
      information.

PMID- 24313899
TI  - Oxygen plasma immersion ion implantation treatment enhances the human bone marrow
      mesenchymal stem cells responses to titanium surface for dental implant
      application.
AB  - OBJECTIVES: The present investigation utilized a novel oxygen plasma immersion
      ion implantation (O-PIII) treatment to create a dense and thin oxide layer on a
      titanium (Ti) surface for dental implant application. MATERIALS AND METHODS: This
      study evaluated the behavior of human bone marrow mesenchymal stem cells (hMSCs)
      on O-PIII-treated Ti. The O-PIII treatments were performed using different oxygen
      ion doses (T(L): 1 * 10(16); T(M): 4 * 10(16); T(H): 1 * 10(17) ions/cm(2)).
      RESULTS: Analysis using an X-ray photoelectron spectrometer (XPS) and high
      resolution X-ray diffractometer (HR-XRD) indicated that the O-PIII-treated
      specimen T(M) had the highest proportion of rutile phase TiO2 component. The O
      PIII-treated specimen T(M) had the greatest protein adsorption capability of the
      test Ti surfaces using XPS analysis and bicinchoninic acid (BCA) protein assay.
      Immunofluorescent staining revealed that hMSCs had the best cell adhesion on the
      O-PIII-treated specimen T(M), whereas green fluorescent protein (GFP)-labeled
      hMSCs experienced the fastest cell migration based on a wound healing assay.
      Other assays, including MTT assay, Alizarin red S staining and Western blot
      analysis, demonstrated that the adhered hMSCs exhibited the greatest cell
      proliferation, mineralization, and differentiation capabilities on the TM
      specimen. CONCLUSIONS: Oxidated Ti (primarily rutile TiO2 ) was produced using a
      facile and rapid O-PIII treatment procedure, which enhances the biocompatibility
      of the Ti surface with potential implications for further dental implant
      application.

PMID- 24313900
TI  - Inversion of a part of the numerator relationship matrix using pedigree
      information.
AB  - BACKGROUND: In recent theoretical developments, the information available (e.g.
      genotypes) divides the original population into two groups: animals with this
      information (selected animals) and animals without this information (excluded
      animals). These developments require inversion of the part of the pedigree-based
      numerator relationship matrix that describes the genetic covariance between
      selected animals (A22). Our main objective was to propose and evaluate
      methodology that takes advantage of any potential sparsity in the inverse of A22
      in order to reduce the computing time required for its inversion. This potential
      sparsity is brought out by searching the pedigree for dependencies between the
      selected animals. Jointly, we expected distant ancestors to provide relationship
      ties that increase the density of matrix A22 but that their effect on A22-1 might
      be minor. This hypothesis was also tested. METHODS: The inverse of A22 can be
      computed from the inverse of the triangular factor (T-1) obtained by Cholesky
      root-free decomposition of A22. We propose an algorithm that sets up the sparsity
      pattern of T-1 using pedigree information. This algorithm provides positions of
      the elements of T-1 worth to be computed (i.e. different from zero). A recursive
      computation of A22-1 is then achieved with or without information on the sparsity
      pattern and time required for each computation was recorded. For three numbers of
      selected animals (4000; 8000 and 12 000), A22 was computed using different
      pedigree extractions and the closeness of the resulting A22-1 to the inverse
      computed using the fully extracted pedigree was measured by an appropriate norm.
      RESULTS: The use of prior information on the sparsity of T-1 decreased the
      computing time for inversion by a factor of 1.73 on average. Computational issues
      and practical uses of the different algorithms were discussed. Cases involving
      more than 12 000 selected animals were considered. Inclusion of 10 generations
      was determined to be sufficient when computing A22. CONCLUSIONS: Depending on the
      size and structure of the selected sub-population, gains in time to compute A22-1
      are possible and these gains may increase as the number of selected animals
      increases. Given the sequential nature of most computational steps, the proposed
      algorithm can benefit from optimization and may be convenient for genomic
      evaluations.

PMID- 24313901
TI  - Do cardiovascular risk factors explain the link between white matter
      hyperintensities and brain volumes in old age? A population-based study.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) and brain atrophy
      frequently coexist in older people. However, it is unclear whether the
      association between these two brain lesions is dependent on the aging process, a
      vascular mechanism or genetic susceptibility. It was therefore investigated
      whether the association between load of WMHs and brain atrophy measures is
      related to age, vascular risk factors (VRFs) or the APOE-epsilon4 allele.
      METHODS: This population-based study included 492 participants (age >=60 years,
      59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE
      genotypes were collected through interviews, clinical examination and laboratory
      tests. WMHs on magnetic resonance images were assessed using manual visual rating
      and automatic volumetric segmentation. Hippocampal and ventricular volumes were
      manually delineated, whereas total gray matter (GM) volume was measured by
      automatic segmentation. Data were analyzed with multivariate linear regression
      models. RESULTS: More global WMHs, assessed using either a visual rating scale or
      a volumetric approach, were significantly associated with lower GM volume and
      higher ventricular volume; the associations remained significant after adjusting
      for age, VRFs and the APOE-epsilon4 allele. In contrast, the association between
      global WMHs and hippocampal volume was no longer significant after adjusting for
      age, whereas adjustment for VRFs and APOE-epsilon4 had no influential effect.
      CONCLUSION: The association of global WMHs with lower GM volume and higher
      ventricular volume is independent of age, VRFs and APOE-epsilon4 allele,
      suggesting that the process of cerebral microvascular disease and
      neurodegeneration are associated independently of the normal aging process,
      vascular mechanisms or genetic susceptibility.

PMID- 24313902
TI  - Response.

PMID- 24313895
TI  - The mechanisms and physiological relevance of glycocalyx degradation in hepatic
      ischemia/reperfusion injury.
AB  - SIGNIFICANCE: Hepatic ischemia/reperfusion (I/R) injury is an inevitable side
      effect of major liver surgery that can culminate in liver failure. The bulk of
      I/R-induced liver injury results from an overproduction of reactive oxygen and
      nitrogen species (ROS/RNS), which inflict both parenchymal and microcirculatory
      damage. A structure that is particularly prone to oxidative attack and
      modification is the glycocalyx (GCX), a meshwork of proteoglycans and
      glycosaminoglycans (GAGs) that covers the lumenal endothelial surface and
      safeguards microvascular homeostasis. ROS/RNS-mediated degradation of the GCX may
      exacerbate I/R injury by, for example, inducing vasoconstriction, facilitating
      leukocyte adherence, and directly activating innate immune cells. RECENT
      ADVANCES: Preliminary experiments revealed that hepatic sinusoids contain a
      functional GCX that is damaged during murine hepatic I/R and major liver surgery
      in patients. There are three ROS that mediate GCX degradation: hydroxyl radicals,
      carbonate radical anions, and hypochlorous acid (HOCl). HOCl converts GAGs in the
      GCX to GAG chloramides that become site-specific targets for oxidizing and
      reducing species and are more efficiently fragmented than the parent molecules.
      In addition to ROS/RNS, the GAG-degrading enzyme heparanase acts at the
      endothelial surface to shed the GCX. CRITICAL ISSUES: The GCX seems to be
      degraded during major liver surgery, but the underlying cause remains ill
      defined. FUTURE DIRECTIONS: The relative contribution of the different ROS and
      RNS intermediates to GCX degradation in vivo, the immunogenic potential of the
      shed GCX fragments, and the role of heparanase in liver I/R injury all warrant
      further investigation.

PMID- 24313903
TI  - Thermal injury to the sigmoideum following hysteroscopic hydrothermal ablation.

PMID- 24313904
TI  - Targeting liposomes loaded with melphalan prodrug to tumour vasculature via the
      Sialyl Lewis X selectin ligand.
AB  - Abstract Earlier we showed that liposome formulation of DL-melphalan lipophilic
      prodrug bearing tetrasaccharide Sialyl Lewis X (SiaLeX) caused prolonged
      therapeutic effect on mammary cancer in mice. Here, we compare antivascular
      effect of SiaLeX-liposomes loaded with diglyceride ester of melphalan (Mlph)
      against SiaLeX-free formulation in Lewis lung carcinoma model. Methods: Liposomes
      of egg phosphatidylcholine/yeast phosphatidylinositol/1,2-dioleoyl glycerol (DOG)
      conjugate of Mlph/+/-SiaLeX-PEG8-15-DOG, 8:1:1:0.2 by mol, were prepared by
      standard extrusion. After two intravenous injections with Mlph or liposomes under
      either standard or delayed treatment protocols, vascular-disrupting effects of
      the preparations were evaluated basing on tumour section histomorphology, lectin
      perfusion assay and immunohistochemistry (anti-CD31 staining) data. Also,
      untreated mice were administered with fluorescently-labelled liposomes to assess
      their distribution in tumour sections with confocal laser scanning microscopy.
      Results: Two injections of SiaLeX-liposomes reproducibly caused severe injuries
      of tumour vessels. SiaLeX-liposomes co-localized with CD31 marker on vascular
      endothelium while the non-targeted formulation extravasated into tumour.
      Discussion: Cytotoxic SiaLeX-liposomes exhibit superior vascular-disrupting
      properties compared to non-targeted liposomes, yet the effect starts to transform
      into gain in tumour growth inhibition only under delayed treatment regimen.
      Conclusion: SiaLeX-ligand provides targeting of cytotoxic liposomes to tumour
      endothelium and subsequent antivascular effect.

PMID- 24313905
TI  - De novo copy number variations in cloned dogs from the same nuclear donor.
AB  - BACKGROUND: Somatic mosaicism of copy number variants (CNVs) in human body organs
      and de novo CNV event in monozygotic twins suggest that de novo CNVs can occur
      during mitotic recombination. These de novo CNV events are important for
      understanding genetic background of evolution and diverse phenotypes. In this
      study, we explored de novo CNV event in cloned dogs with identical genetic
      background. RESULTS: We analyzed CNVs in seven cloned dogs using the nuclear
      donor genome as reference by array-CGH, and identified five de novo CNVs in two
      of the seven clones. Genomic qPCR, dye-swap array-CGH analysis and B-allele
      profile analysis were used for their validation. Two larger de novo CNVs (5.2 Mb
      and 338 Kb) on chromosomes X and 19 in clone-3 were consistently validated by all
      three experiments. The other three smaller CNVs (sized from 36.1 to 76.4 Kb) on
      chromosomes 2, 15 and 32 in clone-3 and clone-6 were verified by at least one of
      the three validations. In addition to the de novo CNVs, we identified a 37 Mb
      sized copy neutral de novo loss of heterozygosity event on chromosome 2 in clone
      6. CONCLUSIONS: To our knowledge, this is the first report of de novo CNVs in the
      cloned dogs which were generated by somatic cell nuclear transfer technology. To
      study de novo genetic events in cloned animals can help understand formation
      mechanisms of genetic variants and their biological implications.

PMID- 24313906
TI  - Effect of exercise training on sports enjoyment and leisure-time spending in
      adolescents with complex congenital heart disease: the moderating effect of
      health behavior and disease knowledge.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of a standardized
      exercise program on sports enjoyment and leisure-time spending in adolescents
      with congenital heart disease and to know what the moderating impact of their
      baseline health behavior and disease knowledge is. METHODS: Included were 93
      patients, aged 10 to 25, with surgical repair for tetralogy of Fallot or with a
      Fontan circulation for single-ventricle physiology, of 5 participating centers of
      pediatric cardiology in The Netherlands. They were randomly allocated, stratified
      for age, gender, and type of congenital heart disease to a 12-week period with
      either: (1) three times per week standardized exercise training or (2) care as
      usual (randomization ratio 2:1). At baseline and after 12 weeks, participants
      completed Web-based questionnaires and were interviewed by phone. OUTCOME
      MEASURES: Primary analyses tested changes from baseline to follow-up in sports
      enjoyment and leisure-time spending in the exercise group vs. control group.
      Secondary analyses concerned the moderating influence of baseline health behavior
      and disease knowledge on changes from baseline to follow-up, and comparison with
      normative data. RESULTS: At follow-up, the exercise group reported a decrease in
      passive leisure-time spending (watching television and computer usage) compared
      with controls. Exercise training had no effect on sports enjoyment and active
      leisure-time spending. Disease knowledge had a moderating effect on improvement
      in sports enjoyment, whereas health behavior did not. Compared with normative
      data, patients obtained similar leisure time scores and lower frequencies as to
      drinking alcohol and smoking. CONCLUSIONS: Exercise training decreased passive,
      but not active, leisure-time spending. It did not influence sports enjoyment.

PMID- 24313908
TI  - The health status and health service needs of primary caregivers of cancer
      survivors: a mixed methods approach.
AB  - This study aimed to measure the health status and care needs of people who
      provide informal care to cancer survivors in the UK. Semi-structured interviews
      were conducted with a purposive sample of 24 cancer professionals to identify the
      care needs of caregivers. In addition, we conducted a postal survey measuring the
      health and well-being [36-item short-form health survey (SF-36)] and health
      service utilisation of 98 primary caregivers of a random sample of cancer
      survivors, 2-20 years post-treatment. Interviews indicated that caregivers' needs
      were largely unmet. In particular, there appeared to be a need in relation to
      statutory healthcare provision, information, psychological support and
      involvement in decision-making. There were no significant differences between
      survivors and caregivers in terms of mental health scores; and caregivers
      performed better on physical health domains compared with cancer survivors.
      Compared with UK norms and norms for caregivers of other chronic conditions,
      cancer caregivers had substantially lower scores on each SF-36 health domain.
      Cancer may impact negatively on an informal caregiver's health long after
      treatment has ended. Providing appropriate and cancer-specific information may
      alleviate difficulties and improve health and well-being. Specific concentration
      should be given to the development and delivery of information support for
      caregivers of post-treatment cancer survivors. 

PMID- 24313907
TI  - The influence of ACE ID and ACTN3 R577X polymorphisms on lower-extremity function
      in older women in response to high-speed power training.
AB  - BACKGROUND: We studied the influence of the ACE I/D and ACTN3 R577X polymorphisms
      (single or combined) on lower-extremity function in older women in response to
      high-speed power training. METHODS: One hundred and thirty-nine healthy older
      Caucasian women participated in this study (age: 65.5 +/- 8.2 years, body mass:
      67.0 +/- 10.0 kg and height: 1.57 +/- 0.06 m). Walking speed (S10) performance
      and functional capacity assessed by the "get-up and go" (GUG) mobility test were
      measured at baseline (T1) and after a consecutive 12-week period of high-speed
      power training (40-75% of one repetition maximum in arm and leg extensor
      exercises; 3 sets 4-12 reps, and two power exercises for upper and lower
      extremity). Genomic DNA was extracted from blood samples, and genotyping analyses
      were performed by PCR methods. Genotype distributions between groups were
      compared by Chi-Square test and the gains in physical performance were analyzed
      by two-way, repeated-measures ANOVA. RESULTS: There were no significant
      differences between genotype groups in men or women for adjusted baseline
      phenotypes (P > 0.05). ACE I/D and ACTN3 polymorphisms showed a significant
      interaction genotype-training only in S10 (P = 0.012 and P = 0.044, respectively)
      and not in the GUG test (P = 0.311 and P = 0.477, respectively). Analyses of the
      combined effects between genotypes showed no other significant differences in all
      phenotypes (P < 0.05) at baseline. However, in response to high-speed power
      training, a significant interaction on walking speed (P = 0.048) was observed
      between the "power" (ACTN3 RR + RX & ACE DD) versus "non-power" muscularity
      oriented genotypes (ACTN3 XX & ACE II + ID)]. CONCLUSIONS: Thus, ACE I/D and
      ACTN3 R577X polymorphisms are likely candidates in the modulation of exercise
      related gait speed phenotype in older women but not a significant influence in
      mobility traits.

PMID- 24313909
TI  - Accidental finding of Hashimoto-like thyroiditis in male B.U.T. 6 turkeys at
      slaughter.
AB  - In the context of a study on the tolerance of rapeseed meal in B.U.T. 6 turkeys,
      thyroid glands were histologically and immunohistochemically examined because of
      potential thyreostatic effects. In all groups including the controls with no
      rapeseed meal in their food, there was a high incidence of lymphocytic
      infiltration and thyroiditis (14% of thyroids with moderate to severe lymphocytic
      thyroiditis). Thirty per cent of mononuclear inflammatory cells were
      immunohistochemically identified as T cells. There were occasional accumulations
      of PAX-5 labelled cells, indicating germinal centre development. These lesions
      resemble Hashimoto's disease in humans. The effect on thyroid function is
      unknown. Mild hypothyreosis might enhance productivity but also explain
      dispositions towards diseases seen in context with thyroid dysfunction such as
      skin diseases (foot pad disease?) and cardiovascular problems. Further studies on
      thyroid function in these turkeys are needed. 

PMID- 24313911
TI  - Inorganic and total arsenic contents in rice-based foods for children with celiac
      disease.
AB  - Celiac disease is an autoimmune disease that affects the villi of the small
      intestine causing abdominal pain, gas, diarrhea, or bad absorption due to gluten
      intolerance. The only treatment for this disease consists of a lifelong gluten
      free diet; this is, celiac people cannot consume products containing gluten, such
      as wheat, barley, and rye, but they can use rice and corn. Thus, rice flour is
      mainly used for the manufacturing of the basic products of this population.
      Unfortunately, rice can contain high contents of total (t-As) and inorganic (i
      As) arsenic. The current study demonstrated that products for celiac children
      with a high percentage of rice contained high concentrations of arsenic (256 and
      128 MUg kg-1). The daily intake of i-As ranged from 0.61 to 0.78 MUg kg-1 body
      weight (bw) in children up to 5 y of age; these values were below the maximum
      value established by the EFSA Panel (8.0 MUg kg-1 bw per day), but it should be
      considered typical of populations with a high exposure to this pollutant.
      Finally, legislation is needed to improve the labeling of these special rice
      based foods for celiac children; label should include information about
      percentage, geographical origin, and cultivar of the used rice.

PMID- 24313912
TI  - A cutaneous presentation of a rare condition.

PMID- 24313910
TI  - Low copy numbers of DC-SIGN in cell membrane microdomains: implications for
      structure and function.
AB  - Presently, there are few estimates of the number of molecules occupying membrane
      domains. Using a total internal reflection fluorescence microscopy (TIRFM)
      imaging approach, based on comparing the intensities of fluorescently labeled
      microdomains with those of single fluorophores, we measured the occupancy of DC
      SIGN, a C-type lectin, in membrane microdomains. DC-SIGN or its mutants were
      labeled with primary monoclonal antibodies (mAbs) in either dendritic cells (DCs)
      or NIH3T3 cells, or expressed as GFP fusions in NIH3T3 cells. The number of DC
      SIGN molecules per microdomain ranges from only a few to over 20, while
      microdomain dimensions range from the diffraction limit to > 1 um. The largest
      fraction of microdomains, appearing at the diffraction limit, in either immature
      DCs or 3 T3 cells contains only 4-8 molecules of DC-SIGN, consistent with our
      preliminary super-resolution Blink microscopy estimates. We further show that
      these small assemblies are sufficient to bind and efficiently internalize a small
      (~ 50 nm) pathogen, dengue virus, leading to infection of host cells.

PMID- 24313913
TI  - Sequential phosphoproteomic enrichment through complementary metal-directed
      immobilized metal ion affinity chromatography.
AB  - Methodologies to enrich heterogeneous types of phosphopeptides are critical for
      comprehensive mapping of the under-explored phosphoproteome. Taking advantage of
      the distinct binding affinities of Ga(3+) and Fe(3+) for phosphopeptides, we
      designed a metal-directed immobilized metal ion affinity chromatography for the
      sequential enrichment of phosphopeptides. In Raji B cells, the sequential Ga(3+)
      Fe(3+)-immobilized metal affinity chromatography (IMAC) strategy displayed a 1.5
      3.5-fold superior phosphoproteomic coverage compared to single IMAC (Fe(3+),
      Ti(4+), Ga(3+), and Al(3+)). In addition, up to 92% of the 6283 phosphopeptides
      were uniquely enriched in either the first Ga(3+)-IMAC (41%) or second Fe(3+)
      IMAC (51%). The complementary properties of Ga(3+) and Fe(3+) were further
      demonstrated through the exclusive enrichment of almost all of 1214 multiply
      phosphorylated peptides (99.4%) in the Ga(3+)-IMAC, whereas only 10% of 5069
      monophosphorylated phosphopeptides were commonly enriched in both fractions. The
      application of sequential Ga(3+)-Fe(3+)-IMAC to human lung cancer tissue allowed
      the identification of 2560 unique phosphopeptides with only 8% overlap. In
      addition to the above-mentioned mono- and multiply phosphorylated peptides, this
      fractionation ability was also demonstrated on the basic and acidic
      phosphopeptides: acidophilic phosphorylation sites were predominately enriched in
      the first Ga(3+)-IMAC (72%), while Pro-directed (85%) and basophilic (79%)
      phosphorylation sites were enriched in the second Fe(3+)-IMAC. This strategy
      provided complementary mapping of different kinase substrates in multiple
      cellular pathways related to cancer invasion and metastasis of lung cancer. Given
      the fractionation ability and ease of tip preparation of this Ga(3+)-Fe(3+)-IMAC,
      we propose that this strategy allows more comprehensive characterization of the
      phosphoproteome both in vitro and in vivo. 

PMID- 24313914
TI  - Detecting and diagnosing hotspots for the enhanced management of hospital
      Emergency Departments in Queensland, Australia.
AB  - BACKGROUND: Predictive tools are already being implemented to assist in Emergency
      Department bed management by forecasting the expected total volume of patients.
      Yet these tools are unable to detect and diagnose when estimates fall short.
      Early detection of hotspots, that is subpopulations of patients presenting in
      unusually high numbers, would help authorities to manage limited health resources
      and communicate effectively about emerging risks. We evaluate an anomaly
      detection tool that signals when, and in what way Emergency Departments in 18
      hospitals across the state of Queensland, Australia, are significantly exceeding
      their forecasted patient volumes. METHODS: The tool in question is an adaptation
      of the Surveillance Tree methodology initially proposed in Sparks and Okugami
      (IntStatl 1:2-24, 2010). for the monitoring of vehicle crashes. The methodology
      was trained on presentations to 18 Emergency Departments across Queensland over
      the period 2006 to 2008. Artificial increases were added to simulated, in-control
      counts for these data to evaluate the tool's sensitivity, timeliness and
      diagnostic capability. The results were compared with those from a univariate
      control chart. The tool was then applied to data from 2009, the year of the H1N1
      (or 'Swine Flu') pandemic. RESULTS: The Surveillance Tree method was found to be
      at least as effective as a univariate, exponentially weighted moving average
      (EWMA) control chart when increases occurred in a subgroup of the monitored
      population. The method has advantages over the univariate control chart in that
      it allows for the monitoring of multiple disease groups while still allowing
      control of the overall false alarm rate. It is also able to detect changes in the
      makeup of the Emergency Department presentations, even when the total count
      remains unchanged. Furthermore, the Surveillance Tree method provides diagnostic
      information useful for service improvements or disease management. CONCLUSIONS:
      Multivariate surveillance provides a useful tool in the management of hospital
      Emergency Departments by not only efficiently detecting unusually high numbers of
      presentations, but by providing information about which groups of patients are
      causing the increase.

PMID- 24313915
TI  - Interfacial segregation in polymer blends driven by acid-base interactions.
AB  - Infrared-visible sum frequency generation spectroscopy (SFG) was used to measure
      the interfacial concentrations of poly(methyl methacrylate) (PMMA)/polystyrene
      (PS) blends next to a sapphire substrate. The acid-base interactions of carbonyl
      groups of PMMA with the hydroxyl groups on the sapphire drive the interfacial
      segregation of PMMA next to the sapphire substrate. Using the shift of sapphire
      surface OH peaks, we have determined the difference in interfacial energy between
      the PMMA/sapphire and the PS/sapphire to be ~44-45 mJ/m(2). These results
      highlight the importance of acid-base interactions and their role in controlling
      the interfacial segregation next to solid substrates in polymer blends.

PMID- 24313916
TI  - Efficacy and safety of certolizumab pegol plus methotrexate in Japanese
      rheumatoid arthritis patients with an inadequate response to methotrexate: the J
      RAPID randomized, placebo-controlled trial.
AB  - OBJECTIVES: This 24-week, multicenter, double-blind, randomized, placebo
      controlled study (NCT00791999) compared efficacy and safety of certolizumab pegol
      (CZP) in combination with methotrexate (MTX) vs placebo plus MTX in Japanese
      rheumatoid arthritis (RA) patients with inadequate response to MTX. METHODS: In
      total, 316 patients were randomized 1:1:1:1 to subcutaneous CZP 100, 200, or 400
      mg (induction dose: 200 mg or 400 mg CZP at Weeks 0, 2, and 4) plus MTX or
      placebo plus MTX every 2 weeks. Primary endpoint was ACR20 response at Week 12.
      RESULTS: ACR20 response rates were 62.5%, 76.8%, 77.6%, and 28.6% at Week 12, and
      61.1%, 73.2%, 71.8%, and 24.7% at Week 24 for CZP 100, 200, and 400 mg, and
      placebo groups, respectively, with statistical significance between each CZP
      group and placebo. Change in Total Sharp Score over 24 weeks was significantly
      smaller in CZP 200 and 400 mg groups vs placebo. Improvements in health-related
      quality of life (HRQoL) were observed in all three CZP groups vs placebo.
      Incidence of adverse events was similar between CZP groups. CONCLUSIONS: CZP plus
      MTX resulted in rapid, sustained reductions in RA signs and symptoms in Japanese
      patients with inadequate response to MTX, with significant inhibition of
      radiographic progression and improved HRQoL.

PMID- 24313917
TI  - Regulatory effect of nicotine on collagen-induced arthritis and on the induction
      and function of in vitro-cultured Th17 cells.
AB  - OBJECTIVES: To determine the effect of nicotine stimulation on collagen-induced
      arthritis (CIA), especially on Th17 cells, and the influence of activated
      acetylcholine receptor signaling on the induction and function of in vitro
      cultured Th17 cells. METHODS: Mice were divided into control and experimental
      (nicotine) group, and PBS or nicotine-PBS was orally administered from Day 21 to
      Day 28. Phenotypic changes in spleen CD4(+) cells were measured by flow
      cytometry. alpha7nAChR expression in Th17 cells was detected using flow
      cytometry, western blotting and real-time PCR. Purified Th17 cells were further
      stimulated with nicotine. The cytometric bead array (CBA) assay was employed to
      measure TNF-alpha levels in mice serum and IL-17A levels in the supernatants of
      nicotine-treated cell cultures. RESULTS: Compared with their counterparts, mice
      receiving oral nicotine showed a delayed progress of arthritis and more
      attenuated signs of histological changes. Moreover, serum TNFalpha levels were
      lower in the nicotine-treated group. Spleen IL-17 level of nicotine-treated mice
      was lower than that of the control group, and the mRNA expression of pro
      inflammatory cytokines (IL-17A and IL-6) in splenocytes were also lower than that
      of the control group. alpha7nAChR expression was detected on in vitro-cultured IL
      17A(+) cells. Cells treated with 10 (- 6) M nicotine expressed lower IL-17A
      levels. Similarly, supernatants from nicotine-treated cell cultures also showed
      lower IL-17A levels. CONCLUSIONS: Nicotine stimulation attenuated signs and
      severity of arthritis in mice. Activation of nicotine acetylcholine receptors on
      in vitro-cultured Th17 cells decreased their pro-inflammatory function, which may
      play a potential role in alleviating arthritis in mice.

PMID- 24313918
TI  - Rheumatic manifestations and an epipharyngeal mass accompanied by myelodysplastic
      syndrome.
AB  - We herein report two cases of myelodysplastic syndrome with rheumatic
      manifestations. (Case 1) A 70-year-old man presented with fever, arthritis and
      bone pain and developed cranial nerve palsy caused by an epipharyngeal mass.
      Steroid therapy led to a prolonged remission of the febrile condition and mass
      lesion. (Case 2) An 82-year-old male was treated for intractable polyarthritis
      and fever with steroid therapy, and serious side effects resulted in lethal
      pneumonia. We herein describe the entire course of steroid therapy in these two
      cases. Various rheumatic manifestations in myelodyaplastic syndrome often require
      empirical steroid therapy. It was effective for the soft tissue mass in Case 1,
      in which indolent lymphoma could not be denied, and was only partially effective
      for Case 2 of the febrile and putatively benign conditions, suggesting
      heterogeneous nature of rheumatic complications in myelodysplastic syndrome. 

PMID- 24313919
TI  - Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome
      successfully treated with tocilizumab: A case report.
AB  - A 38-year-old woman with relapsing longitudinal extensive transverse myelitis and
      Sjogren's syndrome (SS) was admitted with lower extremity muscle weakness.
      Studies showed high serum titer of anti-aquaporin4 antibody and gadolinium
      enhanced-MRI T1-weighted lesions within thoracic cord. Clinical findings
      suggested neuromyelitis optica-spectrum disorder (NMO-SD). High-dose
      corticosteroids, plasma exchange and cyclophosphamide were not effective. After
      starting tocilizumab, her neurological findings gradually improved. This report
      describes the first evidence to show tocilizumab could be effective for NMO-SD
      with SS. 

PMID- 24313920
TI  - Peripheral neuropathies during biologic therapies.
AB  - Peripheral neuropathies should be recognized as the adverse effects of biological
      agents, especially anti-TNF agents. However, no solid clinical databases for
      biological agent-associated peripheral neuropathies (BAPN) have been established
      in Japan. Here we report two cases of peripheral neuropathy associated with anti
      TNF agents. One was peroneal motor neuropathy. The other case was chronic
      inflammatory demyelinating polyradiculoneuropathy. In addition, we summarize the
      previous reports on BAPN and discuss their prevalence rate, pathogenesis and
      management. 

PMID- 24313921
TI  - Effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral
      density in patients with ophthalmologic disease treated with glucocorticoid.
AB  - OBJECTIVES: Glucocorticoid (GC) is usually used for the treatment of systemic
      inflammatory diseases. We performed the prospective study to clarify the effects
      of alendronate or alfacalcidol on bone metabolic indices and bone mineral density
      (BMD) in 90 patients treated with GC for ophthalmologic diseases without systemic
      disorders for 12 months. METHODS: BMD was measured with dual-energy X-ray
      absorptiometry. Serum bone-specific alkaline phosphatase (BAP) and urinary Type I
      collagen cross-linked N-telopeptide (NTx) were measured as bone metabolic
      indices. RESULTS: BMD values in the alendronate group were significantly higher
      than those in the alfacalcidol group during 12 months. Alendronate significantly
      reduced urinary NTX levels from the baseline during 12 months, although
      alfacalcidol did not affect them. Serum BAP levels in the alendronate group were
      significantly lower than those in the alfacalcidol group during 9 months. The
      effects of alendronate on BMD and NTx in male patients seemed to be somewhat
      potent compared with those in female patients. CONCLUSIONS: Alendronate is
      effective to prevent BMD loss and bone resorption induced by GC treatment in
      patients with ophthalmic diseases without systemic disorders. There might be sex
      differences in the potency of alendronate effects.

PMID- 24313922
TI  - Significance of serum and hepatic microRNA-122 levels in patients with non
      alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is believed to be a
      type of metabolic syndrome. MicroRNA-122 (miR-122) is the most abundant microRNA
      in the liver and is an important factor for the metabolism of glucose and lipids.
      In the present study, we examined the correlation between the hepatic and serum
      miR-122 expression levels and the clinicopathological factors of patients with
      NAFLD. METHODS: We extracted the total RNA, along with preserved miRNAs, from
      liver biopsy samples of 67 patients with NAFLD. In 52 of these 67 patients, the
      total RNA was extracted from serum. The miR-122 that was obtained by quantitative
      reverse transcription-polymerase chain reaction was quantified using TaqMan
      MicroRNA assays. RESULTS: A significant correlation was detected between serum
      and hepatic miR-122 expression (correlation coefficient, 0.461; P=0.005).
      Patients with mild steatosis (<33%) showed significantly lower levels of hepatic
      miR-122 compared with patients with severe steatosis (>33%) (hepatic miR-122:
      mild/severe=2.158+/-1.786/4.836+/-7.506, P=0.0473; serum miR-122:
      mild/severe=0.002+/-0.005/0.007+/-0.001, P=0.0491). Moreover, hepatic and serum
      miR-122 levels were significantly higher in patients with mild fibrosis than in
      those with severe fibrosis (hepatic miR-122: mild/severe=5.201+/-7.275/2.394+/
      1.547, P=0.0087; serum miR-122: mild/severe=0.008+/-0.011/0.002+/-0.004,
      P=0.0191). CONCLUSIONS: We found that the hepatic and serum miR-122 levels were
      associated with hepatic steatosis and fibrosis. The serum miR-122 level can be a
      useful predictive marker of liver fibrosis in patients with NAFLD.

PMID- 24313923
TI  - All eggs are made equal: meta-analysis of egg sexual size dimorphism in birds.
AB  - Sex-biased resource allocation in avian eggs has gained increasing interest. The
      adaptive explanations of such allocation are often related to life-history
      strategies of the studied species. In some species, egg sexual size dimorphism
      (SSD) was suggested to promote future size differences between adults of each
      sex. In other species, egg SSD was invoked as an adaptive means by which a mother
      balances sex-specific nestling mortality. According to the first scenario,
      mothers should produce bigger eggs for the bigger sex, thus across species, adult
      SSD should be a significant positive predictor of egg SSD. Under the second
      scenario, mothers should produce bigger eggs for the smaller sex. If different
      species use contrasting strategies, then a universal expectation is that there
      should be a significant relationship between the magnitude of adult SSD and the
      magnitude of egg SSD, irrespective of the direction of those differences. Our aim
      was to examine whether the direction of egg SSD is predicted by the direction of
      adult SSD or whether degree of egg SSD is related to degree of adult SSD. To
      answer that question, we performed meta-analysis of 63 studies, which included
      information on egg SSD of 65 effect sizes from 51 avian species. We found that
      across species, adult SSD does not predict egg SSD. More importantly, the
      observed variation in effect sizes in our data set was largely explained by
      sampling error (variance). Although adult SSD is undoubtedly a prominent feature
      of birds, there is little evidence for egg SSD across avian species. 

PMID- 24313924
TI  - Evaluating the protective efficacy of a trivalent vaccine containing Akabane
      virus, Aino virus and Chuzan virus against Schmallenberg virus infection.
AB  - Schmallenberg virus (SBV), an arthropod borne pathogen, spread rapidly throughout
      the majority of Europe since 2011. It can cause a febrile disease, milk drop,
      diarrhea, and fetal malformation in ruminants. SBV, a member of the Simbu
      serogroup within the genus Orthobunyavirus, is closely related to Akabane virus
      (AKAV) and Aino virus (AINOV) among others. In the present study, 4 Holstein
      Friesian calves were immunized twice four weeks apart with a multivalent,
      inactivated vaccine against AKAV and AINOV. Another 4 calves were kept as
      unvaccinated controls. All animals were clinically, serologically and
      virologically examined before and after challenge infection with SBV. AKAV- and
      AINOV-specific neutralizing antibodies were detected one week before challenge
      infection, while SBV-specific antibodies were detectable only thereafter. SBV
      genome was detected in all vaccinated animals and 3 out of 4 controls in serum
      samples taken after challenge infection. In conclusion, the investigated vaccine
      was not able to prevent an SBV-infection. Thus, vaccines for other related Simbu
      serogroup viruses can not substitute SBV-specific vaccines as an instrument for
      disease control.

PMID- 24313925
TI  - Dextran-based doxorubicin nanocarriers with improved tumor penetration.
AB  - Drug delivery systems with improved tumor penetration are valuable assets as
      anticancer agents. A dextran-based nanocarrier system with aldehyde
      functionalities capable of forming an acid labile linkage with the chemotherapy
      drug doxorubicin was developed. Aldehyde dextran nanocarriers (ald-dex-dox)
      demonstrated efficacy as delivery vehicles with an IC50 of ~300 nM against two
      dimensional (2D) SK-N-BE(2) monolayers. Confocal imaging showed that the ald-dex
      dox nanocarriers were rapidly internalized by SK-N-BE(2) cells. Fluorescence
      lifetime imaging microscopy (FLIM) analysis indicated that ald-dex-dox particles
      were internalized as intact complexes with the majority of the doxorubicin
      released from the particle four hours post uptake. Accumulation of the ald-dex
      dox particles was significantly enhanced by ~30% in the absence of glucose
      indicating a role for glucose and its receptors in their endocytosis. However,
      inhibition of clathrin dependent and independent endocytosis and macropinocytosis
      as well as membrane cholesterol depletion had no effect on ald-dex-dox particle
      accumulation. In three-dimensional (3D) SK-N-BE(2) tumor spheroids, which more
      closely resemble a solid tumor, the ald-dex-dox nanoparticles showed a
      significant improvement in efficacy over free doxorubicin, as evidenced by
      decreased spheroid outgrowth. Drug penetration studies in 3D demonstrated the
      ability of the ald-dex-dox nanocarriers to fully penetrate into a SK-N-BE(2)
      tumor spheroids, while doxorubicin only penetrates to a maximum distance of 50
      MUM. The ald-dex-dox nanocarriers represent a promising therapeutic delivery
      system for the treatment of solid tumors due to their unique enhanced penetration
      ability combined with their improved efficacy over the parent drug in 3D. 

PMID- 24313926
TI  - Syntheses of donor-acceptor-functionalized dihydroazulenes.
AB  - The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has been of
      interest for use in molecular electronics and advanced materials. The switching
      between the two isomers has previously been found to depend strongly on the
      presence of donor and acceptor groups. The fine-tuning of optical and switching
      properties relies on ready access to new derivatives via efficient synthetic
      protocols. The central DHA core is conveniently prepared in a four-step synthesis
      starting from acetophenone and tropylium substrates. Here, the outcome of this
      reaction as a function of the nature of the substituent group on the phenyl unit
      of acetophenone is investigated in detail. A wide variety of functional groups
      (nitro, cyano, halo, alkyl, amido, and thioether) was tolerated, and the route
      provided access to a large selection of substituted DHA derivatives (position 2
      of DHA). These compounds were investigated for their ability to undergo
      subsequent functionalization in the seven-membered ring by a regioselective
      bromination-elimination protocol, introducing a bromo substituent at position 7.
      Halo-substituted DHAs were subjected to palladium-catalyzed cyanation,
      Sonogashira, Cadiot-Chodkiewicz, and Suzuki couplings and for the latter
      reaction; optimized conditions were developed by varying the palladium catalyst.
      In general, our focus was on reducing the formation of fully unsaturated azulene
      byproducts. 

PMID- 24313927
TI  - "Who" can be found in and beyond of an electrocardiographic strip.
AB  - Over the years, an electrocardiogram had become the basic tool to study the heart
      physiology and pathophysiology. Many authors gave a substantial contribution in
      understanding the electrophysiological basis for numerous electrocardiographic
      changes. Some of them were named after authors themselves, or others used the
      names of scientists who first discovered or explained the nature of a particular
      electrocardiographic finding. In this article, electrocardiographic phenomena and
      eponyms used in today's electrocardiography are described. 

PMID- 24313928
TI  - Trauma and mental health sequels require attention and integration in practical
      care.

PMID- 24313929
TI  - Design, synthesis and biological evaluation for docetaxel-loaded brain targeting
      liposome with "lock-in" function.
AB  - Abstract Background: Glucose-modified liposome showed a good brain-targeting
      ability. However, bidirectional transport of glucose transporter-1 (GLUT1) might
      reversely pump drugs out of the brain before releasing from the liposomes.
      Purpose: To overcome the bidirectional delivery of GLUT1, the thiamine disulfide
      system (TDS), with ability of "lock-in", was introduced and a new ligand, L-TDS
      G, was designed and synthesized. Methods: The liposome was prepared and
      characterized for particle size, zeta potential, surface morphological property,
      encapsulation efficiency and release profile. C6 glioma cells were used as an in
      vitro model to access the cellular uptake abilities and cytotoxicity of the
      liposomes. Competition assay was performed to validate the GLUT1-mediated
      transport mechanism. Furthermore, the brain targeting abilities of the liposomes
      were evaluated through in vivo. Results: The preliminary evaluation in vivo
      demonstrated that L-TDS-G-coated liposome has an improved targeting ability and
      significantly increased the area under the concentration-time of docetaxel in
      brain as compared to naked docetaxel, non-coated and L-G coated liposomes. The
      relative uptake efficiency and concentration efficiency were enhanced by 3.82-
      and 4.99-fold compared to that of naked docetaxel, respectively. Conclusion: The
      results of this study indicated that L-TDS-G-coated liposome is a promising drug
      delivery system to enhance the brain concentrations of chemotherapeutic agents.

PMID- 24313930
TI  - A follow-up on patients with severe mental disorders in Sardinia after two
      changes in regional policies: poor resources still correlate with poor outcomes.
AB  - BACKGROUND: This survey followed a cohort of patients with chronic psychosis
      recruited from five catchment areas (DSMs) of the Sardinian community mental
      health services. The objective was to examine whether the amount of resources in
      the different sites may be a determinant of the outcomes. METHODS: Naturalistic
      follow-up study on 309 consecutive users with diagnosis of schizophrenic
      disorder, schizoaffective disorder, bipolar affective disorder with psychotic
      symptoms (DSM-IV TR) of five Sardinian community mental health services. Mental
      state and clinical symptoms along with functioning were assessed using semi
      structured clinical interviews (ANTAS), Clinical Global Impression Severity Scale
      (CGI-S), Global Assessment of Functioning Scale (GAF) and Health of the Nation
      Outcome Scales (HONOS). Assessments were conducted at the beginning of the study
      and after one year. RESULTS: The proportion of professionals working in all DSMs
      participating in the study was found lower than the national Italian standard
      (0.7 vs. 1.0 per 1,500 inhabitants). Follow-up revealed significant differences
      between DSMs in the improvement of the Honos scores (F = 5.932, p = 0.000). These
      differences correlate with the improvement of resources in terms of number of
      professionals during, and one year prior, to the trial. CONCLUSIONS: The study
      shows that mental health services provided in the public sector in Sardinia are
      still very resource-poor, at least in terms of human resources. Our findings
      suggest that mental health service resources influence outcomes as regards the
      social functioning of users. We urge policy makers to take these observations
      into account when planning future services.

PMID- 24313931
TI  - Hepatitis C viral infection and the risk of dementia.
AB  - BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection may cause cognitive
      impairment, but no studies have focused specifically on cognitive impairment
      stemming from HCV. The purpose of this study was to investigate the potential
      increased risk for dementia in HCV-infected patients. METHODS: A population-based
      cohort study based on the Taiwan National Health Insurance Research Database was
      conducted. From all potential participants aged 50 years or more, a total of
      58,570 matched (1:1) pairs of HCV-infected patients and non-HCV-infected patients
      were included. Each subject was individually tracked from 1997 to 2009 to
      identify incident cases of dementia (onset in 1999 or later). Cox proportional
      hazards regressions were employed to calculate the hazard ratios (HRs) and 95%
      confidence intervals (CIs) for the association between HCV infection and
      dementia. RESULTS: There were 2989 dementia cases from the HCV-infected cohort
      during the follow-up period of 533,861.1 person-years; the overall incidence
      rates of dementia differed from the non-HCV cohort (56.0 vs. 47.7 cases per
      10,000 person-years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI
      1.27-1.42) for HCV-infected patients after adjusting for alcohol-related disease,
      liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma.
      CONCLUSIONS: HCV infection may increase the risk for dementia. Further
      mechanistic research is needed.

PMID- 24313932
TI  - Sialyl Lewis X as a predictor of skip N2 metastasis in clinical stage IA non
      small cell lung cancer.
AB  - BACKGROUND: Radical segmentectomy has been performed for small-sized non-small
      cell lung cancer (NSCLC). However, underestimation of mediastinal lymph node
      metastasis in the absence of hilar or interlobar metastasis (skip N2) affects
      surgical strategy. Our aim was to investigate preoperative and intraoperative
      predictors of skip N2 in clinical stage (c-stage) IA NSCLC. METHODS: From 1998 to
      2011, 279 patients (155 men and 124 women) with c-stage IA NSCLC (230 pN0, 17
      pN1, 12 skip N2, 20 non-skip N2) underwent systematic lobectomy (R0 resection) at
      our institute. We compared preoperative serum concentrations of carcinoembryonic
      antigen, cytokeratin 19 fragment, sialyl Lewis X (SLX), and pre- and
      intraoperative clinicopathological features of pN0 and skip N2 patients. Receiver
      operator characteristic (ROC) curve analysis was performed to distinguish between
      the two patient groups. RESULTS: The 5-year survival rate of skip N2 patients was
      78.6%, higher than that of non-skip N2 patients (44.9%), and not significantly
      different than that of pN0 (86.7%) or pN1 patients (82.4%). The mean serum SLX
      concentration in skip N2 patients (28.0 U/ml) was elevated compared to that in
      pN0 patients (22.9 U/ml). In ROC analysis of SLX, the area under the curve was
      0.710, and the optimal cut-off value was 21.4 U/ml (sensitivity, 91.7%;
      specificity, 51.7%). In multivariate analysis, SLX was an independent predictor
      of skip N2 in patients with c-stage IA NSCLC (odds ratio, 9.43; p = 0.006).
      CONCLUSIONS: Skip N2 metastasis is common in patients with c-stage IA NSCLC with
      high serum SLX, and lobectomy with complete dissection of hilar and mediastinal
      lymph nodes should remain the standard surgical procedure for these cases.

PMID- 24313933
TI  - The time effectiveness of three-dimensional telediagnostic postural screening of
      back curvatures and scoliosis.
AB  - BACKGROUND: Postural screening remains a powerful tool that can be used to
      identify children and adolescents with scoliosis or sagittal plane deformities.
      The aim of this study was to assess the time effectiveness of implemented
      telediagnostic screening procedures. MATERIALS AND METHODS: Medical images
      (virtual objects) of acquired clouds of points of 100 subjects of both sexes were
      chosen at random from the database and used for parametric evaluation for this
      study. This study was performed using a newly developed three-dimensional (3D)
      back surface topography measurement system for posture and scoliosis using a
      structured light method. The duration of each step of therapist/nurse/physician
      assisted 3D assessment was measured independently with a stopwatch. Two
      configurations of PC computers and Internet connections were used to test the
      time effectiveness. Scoliotic postures were detected using cutoff values of angle
      of trunk rotation, Posterior Trunk Symmetry Index, and Deformity in the Axial
      Plane Index indices. RESULTS: The overall assessment of all subjects consumed
      from 2 h 55 min 55 s to 3 h 18 min 59 s dependent on PC and Internet connection
      configuration. Average examination time per subject ranged from 2 min 43 s to 4
      min 51 s, respectively. The virtual landmarking and report generation times were
      dependent on the PC configuration (p<0.001). Our study confirmed satisfactory
      time effectiveness of the implemented telediagnostic postural screening
      procedure. We assume that it may influence the cost-effectiveness of the
      screening, which is usually mentioned as an important factor for recommendations
      against postural school screening. Relatively fast Internet connection and a
      medium-level PC configuration are sufficient for achieving a reasonably short
      time of 3D posture assessment of a virtual object representing a real subject's
      back surface. CONCLUSIONS: The efficiency of remote assessment of exact 3D
      surface topography can be used in large-scale studies for posture and scoliosis
      epidemiology.

PMID- 24313935
TI  - How relevant is the framework being used with autism spectrum disorders today?
AB  - Camarata (2014) provides a comprehensive summary of the current state of the
      research on early identification and intervention for children with autism
      spectrum disorders (ASD). Extending on the foundations provided by Camarata, this
      commentary discusses the value of a diagnosis of ASD and questions whether there
      is sufficient evidence on which to base continuing calls for early identification
      and ASD-specific intervention. Gaps are highlighted in the evidence base,
      suggestions made about how to fill those gaps, and an alternative framework is
      proposed for achieving best outcomes for children with early developmental
      problems of the type seen in ASD and their families.

PMID- 24313936
TI  - Supplemental vitamin D enhances the recovery in peak isometric force shortly
      after intense exercise.
AB  - BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) concentrations associate with
      skeletal muscle weakness (i.e., deficit in skeletal muscle strength) after
      muscular injury or damage. Although supplemental vitamin D increases serum
      25(OH)D concentrations, it is unknown if supplemental vitamin D enhances strength
      recovery after a damaging event. METHODS: Reportedly healthy and modestly active
      (30 minute of continuous physical activity at least 3 time/week) adult males were
      randomly assigned to a placebo (n = 13, age, 31(5) y; BMI, 26.9(4.2) kg/m2; serum
      25(OH)D, 31.0(8.2) ng/mL) or vitamin D (cholecalciferol, 4000 IU; n = 15; age,
      30(6) y; BMI, 27.6(6.0) kg/m2; serum 25(OH)D, 30.5(9.4) ng/mL) supplement.
      Supplements were taken daily for 35-d. After 28-d of supplementation, one
      randomly selected leg performed an exercise protocol (10 sets of 10 repetitive
      eccentric-concentric jumps on a custom horizontal plyo-press at 75% of body mass
      with a 20 second rest between sets) intended to induce muscle damage. During the
      exercise protocol, subjects were allowed to perform presses if they were unable
      to complete two successive jumps. Circulating chemistries (25(OH)D and alanine
      (ALT) and aspartate (AST) aminotransferases), single-leg peak isometric force,
      and muscle soreness were measured before supplementation. Circulating
      chemistries, single-leg peak isometric force, and muscle soreness were also
      measured before (immediately) and after (immediately, 1-h [blood draw only], 24
      h, 48-h, 72-h, and 168-h) the damaging event. RESULTS: Supplemental vitamin D
      increased serum 25(OH)D concentrations (P < 0.05; ~70%) and enhanced the recovery
      in peak isometric force after the damaging event (P < 0.05; ~8% at 24-h).
      Supplemental vitamin D attenuated (P < 0.05) the immediate and delayed (48-h, 72
      h, or 168-h) increase in circulating biomarkers representative of muscle damage
      (ALT or AST) without ameliorating muscle soreness (P > 0.05). CONCLUSIONS: We
      conclude that supplemental vitamin D may serve as an attractive complementary
      approach to enhance the recovery of skeletal muscle strength following intense
      exercise in reportedly active adults with a sufficient vitamin D status prior to
      supplementation.

PMID- 24313937
TI  - Editorial: multiple outputs from single studies: acceptable division of findings
      vs. 'salami' slicing.

PMID- 24313934
TI  - Engrafted human cells generate adaptive immune responses to Mycobacterium bovis
      BCG infection in humanized mice.
AB  - BACKGROUND: Currently used mouse models fail to fully reflect human immunity to
      tuberculosis (TB), which hampers progress in research and vaccine development.
      Bone marrow-liver-thymus (BLT) mice, generated by engrafting human fetal liver,
      thymus, and hematopoietic stem cells in severely immunodeficient NOD/SCID/IL
      2Rgamma(-/-) (NSG) mice, have shown potential to model human immunity to
      infection. We engrafted HLA-A2-positive fetal tissues into NSG mice
      transgenically expressing human leukocyte antigen (HLA)-A2.1 (NSG-A2) to generate
      NSG-A2-BLT mice and characterized their human immune response to Mycobacterium
      bovis bacillus Calmette-Guerin (BCG) infection to assess the utility of this
      model for investigating human TB. RESULTS: NSG-A2-BLT mice were infected
      intravenously with BCG and the immune response of engrafted human immune cells
      was characterized. After ex vivo antigenic stimulation of splenocytes, interferon
      (IFN)-gamma-producing cells were detected by ELISPOT from infected, but not
      uninfected NSG-A2-BLT mice. However, the levels of secreted IFN-gamma, determined
      by ELISA, were not significantly elevated by antigenic stimulation. NSG-A2-BLT
      mice were susceptible to BCG infection as determined by higher lung bacillary
      load than the non-engrafted control NSG-A2 mice. BCG-infected NSG-A2-BLT mice
      developed lung lesions composed mostly of human macrophages and few human CD4+ or
      CD8+ T cells. The lesions did not resemble granulomas typical of human TB.
      CONCLUSIONS: Engrafted human immune cells in NSG-A2-BLT mice showed partial
      function of innate and adaptive immune systems culminating in antigen-specific T
      cell responses to mycobacterial infection. The lack of protection was associated
      with low IFN-gamma levels and limited numbers of T cells recruited to the
      lesions. The NSG-A2-BLT mouse is capable of mounting a human immune response to
      M. tuberculosis in vivo but a quantitatively and possibly qualitatively enhanced
      effector response will be needed to improve the utility of this model for TB
      research.

PMID- 24313938
TI  - 'Let other people do it...': the role of emergency department nurses in health
      promotion.
AB  - AIMS AND OBJECTIVES: To explore emergency department nurses' roles in health
      promotion and contributing factors involved. BACKGROUND: In many healthcare
      systems, emergency departments are increasingly urged to play a crucial role in
      health promotion. Although much has been written about health promotion and
      nurses in acute care settings, less has focused on emergency departments. DESIGN:
      A qualitative design was used. METHODS: In-depth semi-structured interviews were
      used with a convenient sample of 15 nurses in a Jordanian emergency department.
      Data were analysed using nvivo 9 (QSR International, Doncaster, Victoria,
      Australia). RESULTS: The analysis identified two themes. The first focused on
      nurses' roles in health promotion, comprising two categories: having no roles and
      'let other people do it'. The second theme focused on the context and constraints
      of health promotion comprising fear of violence, the nature of healthcare service
      and patients' beliefs. The majority of nurses in emergency departments do not
      associate health promotion with their practice, hold some negative attitudes and
      devote more time to clinical tasks than health promotion, which is seen as a
      second priority. CONCLUSIONS: The ideology of medicalised tasks has penetrated
      deeply into the core principles of health promotion, and thus, nurses' roles and
      potential in this area are questioned. RELEVANCE TO CLINICAL PRACTICE: Decision
      makers and nurses within the hospital are urged to address the constraints
      identified in this study and debate them further. Failure to do so may lead to
      emergency nursing not being optimally achieved, with the absence of sustained and
      concerted health promotion work matching patients' cultural needs and
      sensitivities.

PMID- 24313939
TI  - Evaluation of crush syndrome patients with extremity injuries in the 2011 Van
      Earthquake in Turkey.
AB  - AIMS AND OBJECTIVES: To perform a descriptive analysis of crush syndrome patients
      with extremity injuries, which will be used as a reference for future disasters.
      BACKGROUND: In disasters like earthquake, cooperation among medical workers is
      very important for the follow-up and treatment of patients. Knowing the
      complications that may emerge with the crush syndrome is one of the
      responsibilities of the nurses. DESIGN: Descriptive analysis. METHODS: The
      medical records of patients with crush syndrome following the 2011 Van Earthquake
      were retrospectively reviewed. The results were compared with the current
      literature. RESULTS: Of the 46 patients with crush syndrome who had extreme
      trauma, 26 (57%) were men, 20 (43%) were women, and the average age was 38.9 +/-
      12.5. Fasciotomy was performed in 21 of the patients due to progressive
      compartment syndromes. Amputations were performed in seven patients who had
      previously undergone a fasciotomy. Sepsis was observed in seven patients, wound
      infection in 18, pericardial effusion in three and pleural effusion in two.
      Additionally, femoral fracture was observed in one patient, tibial fractures in
      five, haemothorax in three, abdominal traumas in seven and pulmonary embolism in
      one. CONCLUSION: Wound care and antibiotic treatment are important to prevent
      infections in crush injury. In addition to this, dehydration and
      electrocardiography changes in hyperkalaemia are observed in crush syndrome.
      Nurses have significant responsibilities to follow up these observations and
      their implications. RELEVANCE TO CLINICAL PRACTICE: The results of this study may
      provide the basis for developing strategies in future for optimising attempts to
      rescue and the nurse care planning of survivors with crush injuries and crush
      syndrome after earthquakes.

PMID- 24313940
TI  - Life experiences among obstructive sleep apnoea patients receiving continuous
      positive airway pressure therapy.
AB  - AIMS AND OBJECTIVES: To generate a descriptive theoretical framework for
      experiences among obstructive sleep apnoea (OSA) patients undergoing continuous
      positive airway pressure (CPAP) therapy. BACKGROUND: Insufficient information is
      available about subjective experiences among OSA patients undergoing CPAP
      therapy. This study aims to address that lack of insight into patients' feelings.
      DESIGN: A qualitative study using the grounded theory method to establish a
      descriptive theory. METHODS: Twenty-two Taiwanese OSA patients undergoing CPAP
      therapy participated in comprehensive interviews. RESULTS: The patients, aged 37
      68 years, participated in wide-ranging interviews. 'Living with CPAP' was the
      core theme describing the life experiences of OSA patients undergoing CPAP.
      Health warnings were identified as the antecedent condition, with subcategories
      including the following: severe snoring, choking and feelings of a terrible death
      during sleep, day and night sleepiness, easy tiredness, decreased memory, poor
      sleep, dry mouth, dry throat, headache, high blood pressure, poor blood sugar
      level control and falling asleep while driving. Analyses indicated seven
      subcategories of OSA patients with CPAP: (1) seeking medical information, (2)
      difficulties with CPAP, (3) trial and error for the 'right' CPAP, (4) long
      scheduled waiting times, (5) wondering, (6) high expectations, and (7) getting
      back good health. CONCLUSIONS: The results will assist healthcare providers with
      references for OSA health care based on patients' subjective perspectives.
      RELEVANCE TO CLINICAL PRACTICE: After interpreting and analysing results,
      suggestions include the following: (1) provide medical resource education for
      outpatients and inpatients to access self-care knowledge regarding OSA; (2)
      institute professional personnel for providing OSA health education in sleep
      clinics or sleep centres; (3) develop hospital standards for sleep examination
      processes to shorten waiting times; (4) establish case management for pursuing
      OSA patients receiving CPAP; (5) arrange regular forums for patients to share
      their experiences; and (6) provide community health education to promote
      awareness of snoring issues.

PMID- 24313941
TI  - The effect of educational intervention on the pain and rehabilitation performance
      of patients who undergo a total knee replacement.
AB  - AIMS AND OBJECTIVES: To determine the effects of health education on
      postoperative pain, the practice of rehabilitative exercises and functional
      recovery of total knee-replacement patients. BACKGROUND: Most total knee
      replacement patients experience pain and limited physical activities during
      recovery and rehabilitation. Many patients fail to implement an effective
      rehabilitation plan because of the pain and a lack of practical knowledge
      regarding the rehabilitation process. DESIGN: Quasi-experimental design. METHODS:
      We recruited 92 total knee-replacement patients for our study. The experimental
      group (n = 42) received a health-educational intervention. The control group (n =
      50) received routine care. RESULTS: The experimental group reported lower levels
      of postoperative pain than the control group. The stair-climbing ability of the
      experimental group was superior to that of the control group. The experimental
      group also had superior scores for regular straight-leg raises and muscle power
      of the affected leg, compared with the control group. CONCLUSION: The
      preoperative health-educational intervention reduced the level of postoperative
      pain experience by total knee-replacement patients, increased the regularity with
      which they performed rehabilitative exercises and accelerated the recovery of
      their physical functioning. RELEVANCE TO CLINICAL PRACTICE: The health
      educational model can be included in regular clinical management and care of
      total knee-replacement patients.

PMID- 24313942
TI  - Effectiveness of problem-solving technique in caring for family caregivers: a
      clinical trial study in an urban area of Catalonia (Spain).
AB  - AIMS AND OBJECTIVES: To evaluate the effectiveness of the problem-solving
      technique in reducing symptoms of anxiety and depression among primary caregivers
      and to describe and evaluate the process carried out by nurses to find strengths
      and areas of improvement. BACKGROUND: In Spain, home care for the chronically ill
      patients and their family caregivers should be a priority in health and social
      policies due to the increase in ageing population and the progressive increase in
      dependent individuals. One of the areas involved is home-based nursing and
      counselling for family caregivers. DESIGN: This is a clinical trial study (during
      2007-2011) with a mixed analysis methodology. METHODS: Quantitative analysis was
      used to evaluate the effectiveness of the problem-solving technique in reducing
      symptoms of anxiety and depression. The clinical trial involved a control and
      experimental group and pre-post intervention measurements, using the Goldberg
      Scale. The practical application of the technique was evaluated by qualitative
      analysis. RESULTS: There was a statistically significant improvement in symptoms
      of anxiety and depression in the intervention group after application of the
      technique. Positive aspects and resistance factors in its implementation were
      noted. CONCLUSIONS: The problem-solving technique is a cost-effective
      intervention for reducing symptoms of anxiety and depression in family caregivers
      of the chronically ill patients. Positive aspects of the technique were
      satisfaction of the caregiver and nurse, and work done together based on
      reflection. Resistance factors identified were difficulty in maintaining written
      records and subjective perception of a lack of time in everyday practice for its
      consistent application. RELEVANCE TO CLINICAL PRACTICE: The problem-solving
      technique is an important tool to reduce the suffering of family caregivers of
      chronically ill patients and a prevention element of family claudication.

PMID- 24313943
TI  - Commentary on Zhang J, While AE and Norman IJ (2012) development and testing of
      an instrument to assess nurses' knowledge, risk perception, health beliefs and
      behaviours related to influenza vaccination. Journal of Clinical Nursing 21, 2636
      2646.

PMID- 24313944
TI  - Pre-natal undernutrition and post-natal overnutrition are associated with
      permanent changes in hepatic metabolism markers and fatty acid composition in
      sheep.
AB  - AIM: Determine the impacts of pre- and early-post-natal nutrition on selected
      markers of hepatic glucose and fat metabolism. METHODS: Twin-bearing ewes were
      fed 100% (NORM) or 50% (LOW) of protein and energy requirements during the last 6
      weeks of gestation. Twin-lambs received either a high-carbohydrate high-fat
      (HCHF) or conventional (CONV) diet from 3 days to 6 months of age (around
      puberty), whereafter lambs from the four subgroups were slaughtered (16 males/3
      females). Remaining lambs (19 females) were fed a moderate diet and slaughtered
      at 2 years of age (young adults). RESULTS: Pre-natal LOW nutrition was associated
      with increased hepatic triglyceride, ceramide and free fatty acid content in
      adulthood (not observed in lambs), which was accompanied by up-regulated early
      stage insulin signalling as reflected by increased INSRbeta and PI3K-p110 protein
      expression. The HCHF diet increased hepatic triglyceride content in lambs,
      associated with down-regulated expressions of energy-metabolism-related genes
      (GLUT1, PPARalpha, SREBP1c, PEPCK). These post-natal effects were not observed in
      adult HCHF sheep, after they had received a moderate (body-fat correcting) diet
      for 1.5 years. Interestingly, pre-natal LOW nutrition induced permanent
      alterations in hepatic phospholipids' fatty acid composition. Thus, the amount of
      linoleic acid (C18 : 2 ?(9,12)) was significantly increased and composition of
      rumen-derived fatty acids were altered, indicating changed composition of rumenal
      microbiota. CONCLUSION: Hepatic insulin signalling and linoleic and microbial
      derived fatty acid content in phospholipids are targets of foetal programming
      induced by late-gestation undernutrition. Future studies are required to explain
      their cause-effect associations with increased risks of developing hepatic
      steatosis and insulin insensitivity in adulthood.

PMID- 24313945
TI  - Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for
      the diagnosis of non-small cell lung cancer.
AB  - BACKGROUND: The long noncoding RNA MALAT1 (metastasis-associated lung
      adenocarcinoma transcript 1) is described as a potential biomarker for NSCLC (non
      small cell lung cancer). Diagnostic biomarkers need to be detectable in easily
      accessible body fluids, should be characterized by high specificity, sufficient
      sensitivity, and robustness against influencing factors. The aim of this study
      was to evaluate the performance of MALAT1 as a blood based biomarker for NSCLC.
      RESULTS: MALAT1 was shown to be detectable in the cellular fraction of peripheral
      human blood, showing different expression levels between cancer patients and
      cancer-free controls. For the discrimination of NSCLC patients from cancer-free
      controls a sensitivity of 56% was calculated conditional on a high specificity of
      96%. No impact of tumor stage, age, gender, and smoking status on MALAT1 levels
      could be observed, but results based on small numbers. CONCLUSIONS: The results
      of this study indicate that MALAT1 complies with key characteristics of
      diagnostic biomarkers, i.e., minimal invasiveness, high specificity, and
      robustness. Due to its relatively low sensitivity MALAT1 might not be feasible as
      a single biomarker for the diagnosis of NSCLC in the cellular fraction of blood.
      Alternatively, MALAT1 might be applicable as a complementary biomarker within a
      panel in order to improve the entire diagnostic performance.

PMID- 24313946
TI  - Compliant treatment with anti-copper agents prevents clinically overt Wilson's
      disease in pre-symptomatic patients.
AB  - BACKGROUND AND PURPOSE: Wilson's disease (WD) is an inherited copper metabolism
      disorder that leads to dysfunction of affected tissues, mostly in the liver and
      brain. Anti-copper treatment should prevent clinically overt WD in pre
      symptomatic patients but this has not been supported by strong evidence. Our aim
      was to evaluate the long-term effectiveness of treatment in clinically pre
      symptomatic patients, with particular emphasis on patient compliance with
      treatment. METHODS: Data were analyzed for 87 consecutive patients with no
      clinical symptoms of WD who were identified between 1957 and 2009 by family
      screening. All of them since diagnosis were treated with either zinc sulphate
      (Zn) (66.7%) or D-penicillamine (DPA) (33.3%). RESULTS: During a median follow-up
      of 12 years (range 3-52), 55 (63%) patients remained without clinical symptoms,
      13 (15%) developed neuropsychiatric symptoms and 21 (24%) developed hepatic
      dysfunction, including five deaths from hepatic failure. Non-compliance for at
      least three consecutive months was observed in 39 patients, and in 29 cases this
      extended for more than 12 months. Multivariate analysis showed that the odds of
      developing symptomatic WD were independently increased by non-compliance (odds
      ratio 24.0, 95% confidence interval 6.0-99.0). According to Kaplan-Meier analysis
      patients who were compliant to treatment had a significantly higher likelihood of
      remaining symptom-free, and their overall survival was similar to the survival
      rate observed in the general population. CONCLUSION: The use of anti-copper
      agents in clinically pre-symptomatic patients diagnosed with WD allows clinically
      overt disease to be effectively prevented. However, compliance with therapy is
      extremely important.

PMID- 24313947
TI  - The relationship between increased body mass index and frailty on falls in
      community dwelling older adults.
AB  - BACKGROUND: The global population is becoming older and more overweight. The
      inter-relationship between frailty and falls is often seen in the older adult and
      is associated with poor health outcomes. Little is known about this relationship
      for those with excess body mass. This study aimed to assess the relationships
      between BMI, frailty and falls. METHODS: Frailty, body mass index, clinical and
      demographic characteristics were assessed at baseline for 606 community dwelling
      adults aged 60 years and older. Falls were assessed prospectively with a semi
      structured telephone interview two years later. RESULTS: An increase in BMI
      contributed significantly to the identification of frail (Odds Ratio: 4.4; 95%
      Confidence Interval: 1.4, 13.6) older adults. A total of 346 falls by 148
      participants were reported at follow up. Those with an increased BMI were
      significantly less likely to have experienced a fall between baseline and follow
      up assessments (p = 0.03). Despite these opposing trends a BMI greater than or
      equal to 30.0 kg.m2 did not alter the relationship between falls and frailty for
      the current cohort. CONCLUSIONS: This is the first study to assess the falls
      frailty relationship for those with an increased BMI. Obesity was found to be
      protective against falling but not specifically in frail older adults.

PMID- 24313948
TI  - Effect of feeding tannin degrading bacterial culture (Streptococcus gallolyticus
      strain TDGB 406) on nutrient utilization, urinary purine derivatives and growth
      performance of goats fed on Quercus semicarpifolia leaves.
AB  - To study the effect of supplementation of tannin degrading bacterial culture
      (Streptococcus gallolyticus strain TDGB 406) on growth performance, nutrient
      utilization and urinary purine derivatives of goats fed on oak (Quercus
      semicarpifolia) leaves. For growth study, eighteen billy goats (4 month old,
      average body weight 9.50 +/- 1.50 kg) were distributed into three groups of six
      animals each. The animals of group 1 served as control while animals of groups 2
      (T1) and 3 (T2) were given (@ 5 ml/kg live weight) autoclaved and live culture of
      isolate TDGB 406 (10(6) cells/ml) respectively. The animals were fed measured
      quantity of dry oak leaves as the main roughage source and ad libitum maize hay
      along with fixed quantity of concentrate mixture. The feeding of live culture of
      isolate TDGB 406 (probiotic) did not affect dry matter intake and digestibility
      of nutrients except that of dry matter and crude protein, which was higher in T2
      group as compared to control. All the animals were in positive nitrogen balance.
      There was no significant effect of feeding isolate TDGB 406 on urinary purine
      derivatives (microbial protein production) in goats. The body weight gain and
      average live weight gain was significantly higher (p = 0.071) in T2 group as
      compared to control. Feed conversion efficiency was also better in the goats fed
      on live culture of TDGB 406 (T2). The feeding of tannin degrading bacterial
      isolate TDGB 406 as probiotic resulted in improved growth performance and feed
      conversion ratio in goats fed on oak leaves as one of the main roughage source. 

PMID- 24313949
TI  - Insufficient evidence for the use of a physical examination to detect
      maltreatment in children without prior suspicion: a systematic review.
AB  - BACKGROUND: Although it is often performed in clinical practice, the diagnostic
      value of a screening physical examination to detect maltreatment in children
      without prior suspicion has not been reviewed. This article aims to evaluate the
      diagnostic value of a complete physical examination as a screening instrument to
      detect maltreatment in children without prior suspicion. METHODS: We
      systematically searched the databases of MEDLINE, EMBASE, PsychINFO, CINAHL, and
      ERIC, using a sensitive search strategy. Studies that i) presented medical
      findings of a complete physical examination for screening purposes in children 0
      18 years, ii) specifically recorded the presence or absence of signs of child
      maltreatment, and iii) recorded child maltreatment confirmed by a reference
      standard, were included. Two reviewers independently performed study selection,
      data extraction, and quality appraisal using the QUADAS-2 tool. RESULTS: The
      search yielded 4,499 titles, of which three studies met the eligibility criteria.
      The prevalence of confirmed signs of maltreatment during screening physical
      examination varied between 0.8% and 13.5%. The designs of the studies were
      inadequate to assess the diagnostic accuracy of a screening physical examination
      for child maltreatment. CONCLUSIONS: Because of the lack of informative studies,
      we could not draw conclusions about the diagnostic value of a screening physical
      examination in children without prior suspicion of child maltreatment.

PMID- 24313950
TI  - Recent advances in solid-state nuclear magnetic resonance techniques to quantify
      biomolecular dynamics.

PMID- 24313951
TI  - Differential niche dynamics among major marine invertebrate clades.
AB  - The degree to which organisms retain their environmental preferences is of utmost
      importance in predicting their fate in a world of rapid climate change. Notably,
      marine invertebrates frequently show strong affinities for either carbonate or
      terrigenous clastic environments. This affinity is due to characteristics of the
      sediments as well as correlated environmental factors. We assessed the
      conservatism of substrate affinities of marine invertebrates over geological
      timescales, and found that niche conservatism is prevalent in the oceans, and
      largely determined by the strength of initial habitat preference. There is
      substantial variation in niche conservatism among major clades with corals and
      sponges being among the most conservative. Time-series analysis suggests that
      niche conservatism is enhanced during times of elevated nutrient flux, whereas
      niche evolution tends to occur after mass extinctions. Niche evolution is not
      necessarily elevated in genera exhibiting higher turnover in species composition.

PMID- 24313952
TI  - Impact of high hydrostatic pressure and pasteurization on the structure and the
      extractability of bioactive compounds of persimmon "Rojo Brillante".
AB  - Rojo Brillante is an astringent oriental persimmon variety with high levels of
      bioactive compounds such as soluble tannins, carotenoids, phenolic acids, and
      dietary fiber. The purpose of this study was to investigate the effects of high
      hydrostatic pressure (HHP) and pasteurization on the structure of the fruit and
      on the extractability of certain bioactive compounds. The microstructure was
      studied using light microscopy, transmission electron microscopy, and low
      temperature scanning electron microscopy, and certain physicochemical properties
      (carotenoid and total soluble tannin content, antioxidant activity, fiber
      content, color, and texture properties) were measured. The structural changes
      induced by HHP caused a rise in solute circulation in the tissues that could be
      responsible for the increased carotenoid level and the unchanged antioxidant
      activity in comparison with the untreated persimmon. In contrast, the changes
      that took place during pasteurization lowered the tannin content and antioxidant
      activity. Consequently, HHP treatment could improve the extraction of potentially
      bioactive compoundsxsts from persimmons. A high nutritional value ingredient to
      be used when formulating new functional foods could be obtained using HHP. 

PMID- 24313953
TI  - A new way of thinking: hydrocortisone in traumatic brain-injured patients.
AB  - Data suggest that treatment of critical illness-related corticosteroid
      insufficiency after traumatic brain injury (TBI) with a stress dose of
      hydrocortisone may improve the neurological outcome and the mortality rate. The
      mineralocorticoid properties of hydrocortisone may reduce the rate of
      hyponatremia and of brain swelling. The exaggerated inflammatory response may
      cause critical illness-related corticosteroid insufficiency by altering the
      function of the hypothalamic-pituitary-adrenal axis, and hydrocortisone is able
      to restore a balanced inflammatory response rather than inducing
      immunosuppression. Hydrocortisone could also prevent neuronal apoptosis.
      Considering side effects, corticosteroids are not equal; when a high dose of
      synthetic corticosteroids seems detrimental, a strategy using a stress dose of
      hydrocortisone seems attractive. Finally, results from a large multicenter study
      are needed to close the debate regarding the use of hydrocortisone in TBI
      patients. 

PMID- 24313955
TI  - The Fusarium oxysporum effector Six6 contributes to virulence and suppresses I-2
      mediated cell death.
AB  - Plant pathogens secrete effectors to manipulate their host and facilitate
      colonization. Fusarium oxysporum f. sp. lycopersici is the causal agent of
      Fusarium wilt disease in tomato. Upon infection, F. oxysporum f. sp. lycopersici
      secretes numerous small proteins into the xylem sap (Six proteins). Most Six
      proteins are unique to F. oxysporum, but Six6 is an exception; a homolog is also
      present in two Colletotrichum spp. SIX6 expression was found to require living
      host cells and a knockout of SIX6 in F. oxysporum f. sp. lycopersici compromised
      virulence, classifying it as a genuine effector. Heterologous expression of SIX6
      did not affect growth of Agrobacterium tumefaciens in Nicotiana benthamiana
      leaves or susceptibility of Arabidopsis thaliana toward Verticillium dahliae,
      Pseudomonas syringae, or F. oxysporum, suggesting a specific function for F.
      oxysporum f. sp. lycopersici Six6 in the F. oxysporum f. sp. lycopersici- tomato
      pathosystem. Remarkably, Six6 was found to specifically suppress I-2-mediated
      cell death (I2CD) upon transient expression in N. benthamiana, whereas it did not
      compromise the activity of other cell-death-inducing genes. Still, this I2CD
      suppressing activity of Six6 does not allow the fungus to overcome I-2 resistance
      in tomato, suggesting that I-2-mediated resistance is independent from cell
      death. 

PMID- 24313954
TI  - Phenotype and functionality of CD4+ and CD8+ T cells in the upper reproductive
      tract of healthy premenopausal women.
AB  - PROBLEM: The goal of this study was to investigate the phenotype and functional
      responsiveness of CD4(+) and CD8(+) T-cells in the upper reproductive tract of
      healthy premenopausal women. The lower reproductive tract is frequently studied
      as a site of sexually transmitted infections; however, the upper reproductive
      tract may also be a portal of entry and dissemination for pathogens, including
      HIV-1. METHOD OF STUDY: Endometrial biopsy, endocervical curettage, cytobrush,
      and blood were collected during mid-luteal phase from 23 healthy women. T-cells
      were isolated and analyzed by flow cytometry. RESULTS: As compared with their
      counterparts in blood, endometrial and endocervical T-cells had enhanced CCR5
      expression, and were enriched for activated, effector memory cells. Endometrial T
      cells were more responsive to polyclonal stimuli, producing a broad range of
      cytokines and chemokines. CONCLUSION: These findings underscore the
      responsiveness of endometrial T-cells to stimulation, and reveal their activated
      phenotype. These findings also suggest susceptibility of the upper reproductive
      tract to HIV-1 infection.

PMID- 24313956
TI  - Evaluating health-related quality of life in patients with polycystic liver
      disease and determining the impact of symptoms and liver volume.
AB  - BACKGROUND & AIMS: Polycystic liver disease (PLD) follows a progressive course
      ultimately leading to severe hepatomegaly and mechanical complaints in a subset
      of patients. It is still unknown to what extent this compromises health-related
      quality of life (HRQL). Our aim was to determine HRQL in PLD patients and
      investigate its association with concurrent abdominal symptoms and liver volume.
      METHODS: Pooled data of 92 severe PLD patients from two randomized clinical
      trials were used for our cross-sectional analysis. HRQL was assessed using the
      generic short-form health survey (SF-36) resulting in eight scale scores and the
      summarizing physical (PCS) and mental component score (MCS). Subsequently, these
      were compared with the general population. Abdominal symptoms were measured with
      a standardized, 7-point scale questionnaire in 54 patients. We dichotomized
      symptoms for absence or presence and compared them with the component scores.
      Finally, a possible correlation between liver volume and HRQL was explored.
      RESULTS: Demographics showed severe polycystic livers (mean 4906 +/- 2315 ml).
      PCS was significantly lower compared with the general population (P < 0.001), in
      contrast with a similar MCS (P = 0.82). PLD patients had statistically
      significant (P < 0.05) diminished physical functioning, role physical, general
      health, vitality and social functioning scores. Upper- and lower abdominal pain
      and dyspnoea were significantly associated with a reduced PCS (P < 0.01). No
      correlation was found between liver volume and HRQL. CONCLUSION: Polycystic liver
      disease patients had significantly lower HRQL in the physical dimension compared
      with the general population. Abdominal pain and dyspnoea had a significant impact
      on this physical dimension of HRQL.

PMID- 24313957
TI  - Parents of preterm-born children; sources of stress and worry and experiences
      with an early intervention programme - a qualitative study.
AB  - BACKGROUND: Preterm-born children are at increased risk of adverse developmental
      outcomes, and their parents may experience increased stress levels. The Mother
      Infant Transaction Program (MITP) is an early intervention that aims to enhance
      the parent-infant relationship and child development. The present study
      investigated differences in parents' experience of stress and concerns about
      caring for their preterm-born child according to whether they participated in the
      programme. Parental satisfaction with the intervention was also explored.
      METHODS: As part of a follow-up study at 36 months, a randomized controlled trial
      of the MITP-14 parents of 11 children from the intervention group, and 17 parents
      of 14 children from the control group were interviewed by the use of semi
      structured focus group interviews. The interviews were analysed thematically.
      RESULTS: The intervention parents reported that the knowledge, advice, guidance
      and emotional support given during the intervention made them feel less stressed
      and more confident, competent and secure caring for their preterm born child than
      they would otherwise have been. The control parents described feeling less
      involved and emotionally supported, and seemed more anxious about their child's
      development than the intervention parents. All parents were vigilant and alert to
      their child's needs and monitored developmental milestones carefully. CONCLUSION:
      This qualitative exploration of the influences of the MITP revealed a positive
      impact of the intervention and seems to be an important educational and
      supportive initiative. Thus, reducing parental stress and enhancing confidence in
      the parental role.

PMID- 24313958
TI  - Acneiform eruptions: a common cutaneous toxicity of the MEK inhibitor trametinib.
AB  - BACKGROUND: The MEK inhibitor trametinib is currently undergoing clinical trials
      as the treatment of metastatic melanoma both alone and in combination with the
      BRAF inhibitor dabrafenib. One of the most frequent side-effects associated with
      its use as a single agent is the development of acneiform eruptions. These
      eruptions seem to be reduced when dosed in combination with dabrafenib.
      OBJECTIVES: To investigate the prevalence of acneiform eruptions in patients
      taking the MEK inhibitor trametinib, both alone and in combination with
      dabrafenib. METHODS: All patients enrolled in the trametinib alone (n = 13) or
      trametinib and dabrafenib combination (n = 30) clinical trials at a single site
      underwent a retrospective file review. The development and management of acne or
      acneiform eruptions was noted. RESULTS: In total, 77% of the trametinib group
      developed an acneiform eruption on the trial, while only 10% developed acneiform
      lesions in the combination trial. The patients were treated with oral
      doxycycline, topical antibiotics or topical antiseptic washes, with a good
      response. However the condition recurred if these treatments were ceased and the
      patient was still on trametinib therapy. CONCLUSIONS: The MEK inhibitor
      trametinib is associated with the development of acneiform eruptions. When
      combined with dabrafenib the frequency of this side-effect is reduced.

PMID- 24313960
TI  - The mTOR signaling pathway regulates pain-related synaptic plasticity in rat
      entorhinal-hippocampal pathways.
AB  - BACKGROUND: Our previous work demonstrated that persistent peripheral nociception
      (PPN) leads to synaptic plasticity and functional changes in the rat hippocampus.
      The protein kinase mTOR is a critical regulator of protein synthesis-dependent
      synaptic plasticity in the hippocampus as well as synaptic plasticity associated
      with central and peripheral pain sensitization. We examined the role of mTOR
      signaling in pain-associated entorhinal cortex (EC) - hippocampal synaptic
      plasticity to reveal possible cellular mechanisms underlying the effects of
      chronic pain on cognition and emotion. RESULTS: Subcutaneous injection of bee
      venom (BV) into one hind paw to induce PPN resulted in sustained (> 8 h) mTOR
      phospho-activation and enhanced phosphorylation of the mTOR target p70 S6 kinase
      (S6K) in the hippocampus. The magnitude and duration of long-term potentiation
      (LTP) in both EC - dentate gyrus (DG) and EC - CA1 synaptic pathways were
      elevated in BV-treated rats as measured by microelectrode array recording.
      Moreover, the number of potentiated synapses in the hippocampus was markedly
      upregulated by BV-induced PPN. Both elevated mTOR-S6K signaling and enhanced LTP
      induced by BV injection were reversed by systemic injection of the mTOR inhibitor
      rapamycin (RAPA). Rats injected with BV exhibited markedly reduced ambulation and
      exploratory activity in the open field (signs of depression and anxiety) compared
      to controls, and these effects were also reversed by RAPA. CONCLUSION: We suggest
      that PPN-induced enhancement of synaptic plasticity in EC - hippocampal pathways
      and the behavioral effects of PPN are dependent on mTOR-S6K signaling.

PMID- 24313961
TI  - First identification of coexistence of blaNDM-1 and blaCMY-42 among Escherichia
      coli ST167 clinical isolates.
AB  - BACKGROUND: Emergence of multidrug resistance in Enterobacteriaceae limits the
      selection of antimicrobials for treatment of infectious diseases. Identification
      of NDM-1 makes more difficulty in treating multidrug-resistant Enterobacteriaceae
      infections. Carbapenem-resistant Escherichia coli clinical isolates from a
      tertiary hospital in Wenzhou, east China, were investigated for NDM-1 production.
      RESULTS: The two tested isolates were negative for modified Hodge test, but
      positive for a double-disc synergy test used for detecting metallo-beta-lactamase
      production. E. coli WZ33 and WZ51 exhibited discrepant-level resistance to most
      clinically frequent used antimicrobials, but still susceptible to
      trimethoprim/sulfamethoxazole, amikacin, fosfomycin, tigecycline and polymyxin B.
      E. coli WZ33 and WZ51 were positive for bla(NDM-1) determined by PCR and DNA
      sequencing. Other than bla(NDM-1), E. coli WZ33 also harbored bla(CTX-M-14) and
      bla(CMY-42), while E. coli WZ51 simultaneously harbored blaSHV-12,bla(CTX-M-14)
      and bla(CMY-42). Carbapenem resistance for E. coli WZ51 and WZ33 could not be
      transferred to E. coli recipients through conjugation, but could be transferred
      to E. coli recipients by chemical transformation. The EcoR1-digested DNA pattern
      of plasmids from the transformant of E. coli WZ51 was different from that of E.
      coli WZ51. MLST showed that E. coli WZ33 and WZ51 belonged to an animal
      associated clone (ST167). CONCLUSION: The present study is the first report of
      bla(NDM-1) carriage in E. coli ST167 isolates and coexistence of bla(NDM-1) and
      bla(CMY-42) in same isolate. Systemic surveillance should focus on the
      dissemination of bla(NDM-1) among Enterobacteriaceae, especially E. coli ST167
      clone associated with animal infection.

PMID- 24313962
TI  - Development of HomeSTEAD's physical activity and screen time physical environment
      inventory.
AB  - BACKGROUND: The home environment has a significant influence on children's
      physical activity, sedentary behavior, dietary intake, and risk for obesity and
      chronic disease. Our understanding of the most influential factors and how they
      interact and impact child behavior is limited by current measurement tools,
      specifically the lack of a comprehensive instrument. HomeSTEAD (the Home Self
      administered Tool for Environmental assessment of Activity and Diet) was designed
      to address this gap. This new tool contains four sections: home physical activity
      and media equipment inventory, family physical activity and screen time
      practices, home food inventory, and family food practices. This paper will
      describe HomeSTEAD's development and present reliability and validity evidence
      for the first section. METHODS: The ANGELO framework guided instrument
      development, and systematic literature reviews helped identify existing items or
      scales for possible inclusion. Refinement of items was based on expert review and
      cognitive interviews. Parents of children ages 3-12 years (n = 125) completed the
      HomeSTEAD survey on three separate occasions over 12-18 days (Time 1, 2, and 3).
      The Time 1 survey also collected demographic information and parent report of
      child behaviors. Between Time 1 and 2, staff conducted an in-home observation and
      measured parent and child BMI. Kappa and intra-class correlations were used to
      examine reliability (test-retest) and validity (criterion and construct).
      RESULTS: Reliability and validity was strong for most items (97% having ICC >
      0.60 and 72% having r > 0.50, respectively). Items with lower reliability
      generally had low variation between people. Lower validity estimates (r < 0.30)
      were more common for items that assessed usability and accessibility, with
      observers generally rating usability and accessibility lower than parents. Small
      to moderate, but meaningful, correlations between physical environment factors
      and BMI, outside time, and screen time were observed (e.g., amount of child
      portable play equipment in good condition and easy to access was significantly
      associated with child BMI: r = -0.23), providing evidence of construct validity.
      CONCLUSIONS: The HomeSTEAD instrument represents a clear advancement in the
      measurement of factors in the home environment related to child weight and weight
      related behaviors. HomeSTEAD, in its entirety, represents a useful tool for
      researchers from which they can draw particular scales of greatest interest and
      highest relevance to their research questions.

PMID- 24313963
TI  - Breast cancer in lesbians and bisexual women: systematic review of incidence,
      prevalence and risk studies.
AB  - BACKGROUND: The UK Parliamentary Enquiry and USA Institute of Medicine state that
      lesbians may be at a higher risk of breast cancer but there is insufficient
      information. Lesbians and bisexual (LB) women have behavioural risk-factors at
      higher rates compared to heterosexuals such as increased alcohol intake and
      higher stress levels. Conversely, breast cancer rates are higher in more affluent
      women yet income levels in LB women are relatively low. This systematic review
      investigated all evidence on whether there is, or likely to be, higher rates of
      breast cancer in LB women. METHODS: Cochrane library (CDSR, CENTRAL, HTA, DARE,
      NHSEED), MEDLINE, EMBASE, PsychINFO, CAB abstracts, Web of Science (SCI, SSCI),
      SIGLE and Social Care Online databases were searched to October 2013. Unpublished
      research and specific lesbian, gay and bisexual websites were checked, as were
      citation lists of relevant papers. Included were studies in LB populations
      reporting breast cancer incidence or prevalence rates, risk model results or risk
      factor estimates. Inclusions, data-extraction and quality assessment were by two
      reviewers with disagreements resolved by discussion. RESULTS: Searches found 198
      references. No incidence rates were found. Nine studies gave prevalence estimates
      - two showed higher, four showed no differences, one showed mixed results
      depending on definitions, one had no comparison group and one gave no sample
      size. All studies were small with poor methodological and/or reporting quality.
      One incidence modelling study suggested a higher rate.Four risk modelling studies
      were found, one Rosner-Colditz and three Gail models. Three suggested higher and
      one lower rate in LB compared to heterosexual women. Six risk-factor estimates
      suggested higher risk and one no difference between LB and heterosexual women.
      CONCLUSIONS: The only realistic way to establish rates in LB women would be to
      collect sexual orientation within routine statistics, including cancer registry
      data, or from large cohort studies.

PMID- 24313964
TI  - Effects of fumaric acid on rumen fermentation, milk composition and metabolic
      parameters in lactating cows.
AB  - The aim of this study was to determine the influence of fumaric acid (FA) on
      ruminal fermentation and its effects on the acid-base balance of seven ruminally
      and duodenally fistulated multiparous German Holstein cows. The experiment was
      conducted in a change-over design with three periods in which the animals were
      randomly arranged in one of three treatments: Control (C; without FA), 300 or 600
      g FA per day. The diets consisted of 7.4 kg DM grass silage, 4.2 kg concentrate
      mixture and 0, 300 or 600 g FA or wheat starch as isocaloric compensation per day
      and cow. FA supplementation decreased the rumen pH, acetic acid and butyric acid
      and increased propionic acid in rumen fluid. The results of the single-strand
      conformation polymorphism analysis (SSCP) did not show an influence of FA on the
      microbial population in the rumen. The beta-hydroxybutyrate (BHB) concentration
      in blood and the pH of the urine decreased, while the blood gases were unaffected
      by supplementation of the acid. The microbial protein per MJ ME decreased in the
      duodenum with FA supplementation. The milk fat concentration decreased after
      addition of FA. We conclude that in this study feeding of up to 600 g FA per day
      did not result in an acidosis. It seems that up to 600 g FA per day did not have
      a significant influence on the acid-base balance of dairy cows. 

PMID- 24313965
TI  - Intention to seek professional psychological help among college students in
      Turkey: influence of help-seeking attitudes.
AB  - BACKGROUND: Depression rates are high among college students in Turkey, but often
      students do not seek mental health care. This study aimed to examine the
      association between attitudes toward seeking professional psychological help and
      intention to seek professional psychological help among such college students. We
      also examined the factors associated with students' professional psychological
      help-seeking attitudes. We conducted this cross-sectional study among 456
      conveniently sampled graduate and undergraduate students in Ankara. We collected
      students' data using self-administered, structured questionnaires in the Turkish
      language and then analyzed the data using both descriptive and multivariate
      methods. RESULTS: In the multiple linear regression analyses, students' attitudes
      towards seeking professional psychological help were positively associated with
      intention to seek such help (p < 0.001). Other factors positively associated with
      students' attitudes towards seeking professional psychological help included the
      following: age (p < 0.001), perceived social support from family (p < 0.05),
      perceived social support from friends (p < 0.01), and perceived social support
      from significant other (p < 0.05). Students with less positive attitudes toward
      seeking professional psychological help were more likely to be men (p < 0.001),
      undergraduate students (p < 0.001), and students who were not aware of the
      presence of the on-campus counseling center (p < 0.01). CONCLUSIONS: Students'
      positive attitudes toward seeking professional psychological help were positively
      associated with their intentions to seek such help. To encourage utilization of
      the counseling center inside the campus more frequently when in need,
      interventions might be necessary to improve students' attitudes toward seeking
      professional psychological help-in particular among young male students.

PMID- 24313966
TI  - Greater occipital nerve blocks in chronic cluster headache: a prospective open
      label study.
AB  - BACKGROUND AND PURPOSE: Greater occipital nerve blockade (GONB) has been shown to
      be effective in episodic cluster headache. However, its use in chronic cluster
      headache (CCH) is less certain. The study aims to prospectively assess the
      efficacy and consistency of response to GONB in a large series of CCH patients.
      METHODS: CCH patients who had a unilateral GONB and were referred to the National
      Hospital for Neurology and Neurosurgery were studied prospectively. Headache
      characteristics were collected using headache diaries. Responders were considered
      to be patients with a complete or partial response lasting at least 7 days. In a
      subgroup of responders the outcomes of serial GONB performed at 3-monthly
      intervals were also analysed. RESULTS: Eighty-three CCH patients were studied.
      After the first GONB, a positive response was observed in 47 (57%) patients: 35
      (42%) were rendered pain free, 12 (15%) had a partial benefit and one patient
      obtained <50% improvement. The duration of a positive response lasted a median of
      21 days (range 7-504 days). There was a transient worsening of condition in 6% of
      patients. The overall rate and average duration of response remained consistent
      after the second [n = 37; 31 responders (84%); median duration 21 days], third [n
      = 28; 20 responders (71%); median duration 25 days] and fourth [n = 14; 10
      responders (71%); median duration 23 days] injections. CONCLUSION: GONB seems to
      be an efficacious treatment with reproducible effects in CCH patients. Performed
      three monthly, GONB may have a useful role in the management of CCH.

PMID- 24313967
TI  - Of ions and temperature: the complicated interplay of temperature, fluids, and
      electrolytes on myocardial function.
AB  - This article discusses the potential of levosimendan to treat calcium-induced
      myocardial dysfunction associated with deep hypothermia. Moderate hypothermia (30
      to 34 degrees C) usually improves myocardial contractility and stabilizes heart
      rhythm, but deep hypothermia can cause severe myocardial dysfunction, which is
      mediated by intracellular calcium overload. In experimental studies, levosimendan
      appears effective in reversing this. Clinical studies are needed to confirm these
      findings and to determine whether levosimendan could also be used for accidental
      hypothermia and perhaps to mitigate diastolic dysfunction under moderate
      hypothermia. 

PMID- 24313968
TI  - Release of allyl isothiocyanate from mustard seed meal powder.
AB  - Allyl isothiocyanate (AITC) is a wide-spectrum antimicrobial compound found in
      mustard seeds, produced when their tissues are disrupted. The formation of AITC
      in mustard seed is mediated by the myrosinase enzyme which catalyzes the release
      of volatile AITC from a glucosinolate-sinigrin. Since water is a substrate in the
      reaction, humidity from the air can be used to activate the release of AITC from
      mustard seed. In this study, defatted and partially defatted mustard seed meals
      were ground into powders with particle size ranging from 5 to 300 MUm. The
      mustard seed meal powder (MSMP) samples were enclosed within hermetically sealed
      glass jars wherein the headspace air was adjusted to 85% or 100% relative
      humidity at 5, 20, or 35  degrees C. Data from gas chromatography analysis showed
      that AITC release rate and amount increased with increasing relative humidity and
      temperature. Moreover, the release rate can be manipulated by particle size and
      lipid content of the MSMP samples. The amount of AITC released ranged from 2 to
      17 mg/g MSMP within 24 h under the experimental conditions tested. In view of the
      antimicrobial properties of AITC, the mustard meal powder may be used as a
      natural antimicrobial material for extending the shelf life of food products. 

PMID- 24313969
TI  - Conservative management, surgery and radiosurgery for treatment of vestibular
      schwannomas: a model-based approach to cost-effectiveness.
AB  - OBJECTIVE: To undertake a cost-effectiveness analysis comparing conservative
      management, surgery and radiosurgery for treating small-to-medium (1-20 mm)-sized
      vestibular schwannomas. DESIGN: Model-based economic evaluation using individual
      level data from a Birmingham-based longitudinal patient database and from
      published sources. Both a decision tree and state-transition (Markov) model were
      developed, from an National Health Service (NHS) perspective. Sensitivity
      analyses were also carried out. SETTING: Secondary care treatment for patients
      with small-to-medium-sized vestibular schwannomas. PARTICIPANTS: Three
      hypothetical cohorts of adult patients receiving conservative management,
      radiosurgery or surgery treatment, aged 58 years as starting age within model.
      MAIN OUTCOME MEASURES: Cost-effectiveness based on cost per quality-adjusted life
      year (QALY). RESULTS: Conservative management is the preferred strategy for the
      treatment of small-to-medium-sized vestibular schwannomas. Conservative
      management is both cheaper (-L 722 and -L 2764) and more effective (0.136 and
      0.554 quality-adjusted life years) than both radiosurgery and surgery,
      respectively. A conservative strategy can therefore be considered as highly cost
      effective. This result is sensitive to the assumed quality-of-life parameters in
      the model. Sensitivity analysis suggests that the probability of a conservative
      strategy being the most cost-effective approach compared with surgery and
      radiosurgery at a willingness to pay of L 20 000/quality-adjusted life year
      gained is 80% and 55%, respectively. CONCLUSIONS: A conservative approach is the
      preferred strategy for treatment of small-to-medium vestibular schwannomas. This
      result is sensitive to quality-of-life values used in the analysis. More research
      is required to assess the impact of treatment upon patients' health-related
      quality of life over time.

PMID- 24313970
TI  - The impact of obesity on patient survival in liver transplant recipients: a meta
      analysis.
AB  - BACKGROUND & AIMS: It is controversial if obesity has an impact on overall
      survival after liver transplantation (LT). The goal of this study was to
      determine if obesity impacts liver transplant recipient survival. Through
      subgroup analysis, we also evaluated different body mass index (BMI) thresholds
      and the confounding effect of ascites on survival. METHODS: A systematic
      literature search from 1990 until July 2013. The main outcome was to evaluate the
      impact of obesity on survival in adult LT recipients. Dochotomous outcomes were
      reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS:
      Thirteen studies with a total 2275 obese and 72 212 non obese patients were
      included in the analysis. The combined analysis showed no difference in mortality
      between control and increased weight patients (RR = 0.97, 95% CI [0.82, 1.13], P
      = 0.66) at last follow-up. Moreover, no differences in mortality were noted in
      subgroup analysis comparing different BMI thresholds. There was also no
      differences in survival when BMI was adjusted for ascites or in studies where the
      liver disease severity was similar. Obese patients had worse survival than
      nonobese patients in pooled analysis of studies which had similar causes of liver
      disease (RR = 0.69, 95% CI [0.52, 0.92], P = 0.01). CONCLUSION: The results of
      our pools analysis suggest that BMI does not specifically impact patient
      survival. However, obese patients have worse survival when analysis was performed
      in studies whose cohorts of obese and nonobese patients had similar causes of
      liver disease.

PMID- 24313972
TI  - Career perspective: Ralph F. Goldman-military ergonomics.
AB  - Military Ergonomics is a name I made up when the Commander at the US Army
      Research Institute of Environmental Medicine (USARIEM) told me 'The Surgeon
      General wants to give you a Research Division of your own.' I demurred, saying
      'That would make me an Administrator, and I prefer research,' but the C.O. (who
      was a friend) insisted, saying that what I wanted had no impact on what the
      General wanted and I had to become the Director of either the Heat, Cold, Work,
      or Altitude Divisions. Thinking fast, I said 'I want the "Military Ergonomics
      Division" ', and when he asked 'What's that?' I said 'That's good- it means I can
      continue my studies on the effects of heat, cold, terrain, load carried,
      clothing, food, & water intake on troops.' 

PMID- 24313971
TI  - Sex differences in circumstances and consequences of outdoor and indoor falls in
      older adults in the MOBILIZE Boston cohort study.
AB  - BACKGROUND: Despite extensive research on risk factors associated with falling in
      older adults, and current fall prevention interventions focusing on modifiable
      risk factors, there is a lack of detailed accounts of sex differences in risk
      factors, circumstances and consequences of falls in the literature. We examined
      the circumstances, consequences and resulting injuries of indoor and outdoor
      falls according to sex in a population study of older adults. METHODS: Men and
      women 65 years and older (N = 743) were followed for fall events from the
      Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly
      (MOBILIZE) Boston prospective cohort study. Baseline measurements were collected
      by comprehensive clinical assessments, home visits and questionnaires. During the
      follow-up (median = 2.9 years), participants recorded daily fall occurrences on a
      monthly calendar, and fall circumstances were determined by a telephone
      interview. Falls were categorized by activity and place of falling. Circumstance
      specific annualized fall rates were calculated and compared between men and women
      using negative binomial regression models. RESULTS: Women had lower rates of
      outdoor falls overall (Crude Rate Ratio (RR): 0.72, 95% Confidence Interval (CI):
      0.56-0.92), in locations of recreation (RR: 0.34, 95% CI: 0.17-0.70), during
      vigorous activity (RR: 0.38, 95% CI: 0.18-0.81) and on snowy or icy surfaces (RR:
      0.55, 95% CI: 0.36-0.86) compared to men. Women and men did not differ
      significantly in their rates of falls outdoors on sidewalks, streets, and curbs,
      and during walking. Compared to men, women had greater fall rates in the kitchen
      (RR: 1.88, 95% CI: 1.04-3.40) and while performing household activities (RR:
      3.68, 95% CI: 1.50-8.98). The injurious outdoor fall rates were equivalent in
      both sexes. Women's overall rate of injurious indoor falls was nearly twice that
      of men's (RR: 1.98, 95% CI: 1.44-2.72), especially in the kitchen (RR: 6.83, 95%
      CI: 2.05-22.79), their own home (RR: 1.84, 95% CI: 1.30-2.59) and another
      residential home (RR: 4.65, 95% CI: 1.05-20.66) or other buildings (RR: 2.29, 95%
      CI: 1.18-4.44). CONCLUSIONS: Significant sex differences exist in the
      circumstances and injury potential when older adults fall indoors and outdoors,
      highlighting a need for focused prevention strategies for men and women.

PMID- 24313973
TI  - Effects of polymer-coated metal oxide nanoparticles on goldfish (Carassius
      auratus L.) neutrophil viability and function.
AB  - Exposure effects from polyacrylic acid (PAA) metal-oxide nanoparticles (TiO2,
      CeO2, Fe2O3, ZnO) on fish neutrophil viability and effector functions
      (degranulation, respiratory burst, inflammatory gene expression) were
      investigated using primary kidney goldfish (Carassius auratus L.) neutrophils as
      a model. Several studies have reported cytotoxic effects of NPs but there are
      limited reports on their potential to perturb the innate immune system of aquatic
      organisms. PAA-TiO2 significantly decreased neutrophil viability in a time and
      dose-dependent manner at all measured time points (0-48 h) and concentrations (0
      200 ug/mL). Maximum viability decreased by (mean +/- SEM): 67.1 +/- 3.3%, 78.4 +/
      4.2% and 74.9 +/- 5.0% when exposed to 50, 100 and 200 ug/mL for 48 h,
      respectively. PAA-ZnO also significantly decreased neutrophil viability but only
      at 48 h exposures at higher concentrations. Neutrophil degranulation increased by
      approximately 3% after 30 min and by 8% after 4 h when exposed to sublethal doses
      (10 ug/mL) of PAA-CeO2 or PAA-Fe2O3. All PAA-NPs induced an increase in
      neutrophil respiratory burst when exposed to 10 ug/mL for 30 and 60 min, however,
      PAA-Fe2O3 was the only NP where the response was significant. Lastly, NPs altered
      the expression of a number of pro-inflammatory and immune genes, where PAA-TiO2
      most significantly increased the mRNA levels of pro-inflammatory genes (il-1b,
      ifng) in neutrophils by 3 and 2.5 times, respectively. Together, these data
      demonstrate that goldfish neutrophils can be negatively affected from exposures
      to PAA-coated NPs and are functionally responsive to specific core-material
      properties at sublethal doses. These changes could perturb the innate response
      and affect the ability of fish to respond to pathogens.

PMID- 24313974
TI  - British Association of Dermatologists' guidelines for the management of squamous
      cell carcinoma in situ (Bowen's disease) 2014.

PMID- 24313975
TI  - Household cost of out-patient treatment of Buruli ulcer in Ghana: a case study of
      Obom in Ga South Municipality.
AB  - BACKGROUND: The economic burden of diseases has become increasingly relevant to
      policy makers as healthcare expenditure keep rising in the face of limited and
      competing resources. Buruli ulcer (BU), a neglected but treatable tropical
      disease caused by Mycobacterium ulcerans, the only known environmental
      mycobacterium is capable of causing long term disability when left untreated.
      However, most BU studies have tended to focused on its bacteriology,
      epidemiology, entomology and other social determinants to the neglect of its
      economic evaluation. This paper reports estimated the household economic costs of
      BU and describe the intangible cost suffered by BU patients in an endemic area.
      METHODS: Retrospective one year cost data was used. A total of 63 confirmed BU
      cases were randomly sampled for the study. Economic cost and cost burden of BU
      were estimated. Sensitivity analysis was conducted to test the robustness of the
      cost estimates. Intangible cost measured stigmatization, pain, functional
      limitation and social isolation of children. RESULTS: The annual total household
      economic cost was US$35,915.98, of which about 65% was cost incurred by children
      with a mean cost of US$521.04. The mean annual household cost was US$570.09. The
      direct cost was 96% of the total cost. Non-medical cost accounts for about 97% of
      the direct cost with a mean cost of US$529.27. The mean medical cost was
      US$18.94. The main cost drivers of the household costs were transportation (78%)
      and food (12%). Caregivers and adult patients lost a total of 535 productive days
      seeking care, which gives an indirect cost valued at US$1,378.67 with a mean of
      US$21.88. A total of 365 school days (about 1 year) were lost by 19 BU patients
      (mean, 19.2 days). Functional loss and pain were low, and stigma rated moderate.
      Most children suffering from BU (84%) were socially isolated. CONCLUSION:
      Household cost burden of out-patient BU ulcer treatment was high. Household cost
      of BU is therefore essential in the design of its intervention. BU afflicted
      children experience social isolation.

PMID- 24313976
TI  - Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in
      the mice hippocampus after intracerebral injection of kainic acid.
AB  - BACKGROUND: The roles of caspase 3 on the kainic acid-mediated neurodegeneration,
      dendritic plasticity alteration, neurogenesis, microglial activation and gliosis
      are not fully understood. Here, we investigate hippocampal changes using a mouse
      model that receive a single kainic acid-intracerebral ventricle injection. The
      effects of caspase 3 inhibition on these changes were detected during a period of
      1 to 7 days post kainic acid injection. RESULT: Neurodegeneration was assessed by
      Fluoro-Jade B staining and neuronal nuclei protein (NeuN) immunostaining.
      Neurogenesis, gliosis, neuritic plasticity alteration and caspase 3 activation
      were examined using immunohistochemistry. Dendritic plasticity, cleavvage
      dependent activation of calcineurin A and glial fibrillary acidic protein
      cleavage were analyzed by immunoblotting. We found that kainic acid not only
      induced neurodegeneration but also arouse several caspase 3-mediated molecular
      and cellular changes including dendritic plasticity, neurogenesis, and gliosis.
      The acute caspase 3 activation occurred in pyramidal neurons as well as in hilar
      interneurons. The delayed caspase 3 activation occurred in astrocytes. The co
      injection of caspase 3 inhibitor did not rescue kainic acid-mediated
      neurodegeneration but seriously and reversibly disturb the structural integrity
      of axon and dendrite. The kainic acid-induced events include microglia
      activation, the proliferation of radial glial cells, neurogenesis, and
      calcineurin A cleavage were significantly inhibited by the co-injection of
      caspase 3 inhibitor, suggesting the direct involvement of caspase 3 in these
      events. Alternatively, the kainic acid-mediated astrogliosis is not caspase 3
      dependent, although caspase 3 cleavage of glial fibrillary acidic protein
      occurred. CONCLUSIONS: Our results provide the first direct evidence of a causal
      role of caspase 3 activation in the cellular changes during kainic acid-mediated
      excitotoxicity. These findings may highlight novel pharmacological strategies to
      arrest disease progression and control seizures that are refractory to classical
      anticonvulsant treatment.

PMID- 24313977
TI  - Genetic and environmental influences on eating behaviors in 2.5- and 9-year-old
      children: a longitudinal twin study.
AB  - BACKGROUND: Eating behaviors during childhood are related both to children's diet
      quality and to their weight status. A better understanding of the determinants of
      eating behavior during childhood is essential for carrying out effective dietary
      interventions. METHODS: We assessed the contribution of genetic and environmental
      factors to variations in selected eating behaviors in early and late childhood.
      Information on eating behaviors came from questionnaires administered to parents
      of children participating in the Quebec Newborn Twin Study when the twins were
      2.5 and 9 years old (n = 692 children). Dichotomous variables were derived and
      analyzed using structural equation modeling, as part of a classic twin study
      design. We performed univariate and bivariate longitudinal analyses to quantify
      sources of variation and covariation across ages, for several eating behavior
      traits. RESULTS: We found moderate to strong heritability for traits related to
      appetite such as eating too much, not eating enough and eating too fast.
      Univariate analysis estimates varied from 0.71 (95% CI: 0.49, 0.87) to 0.89
      (0.75, 0.96) in younger children and from 0.44 (0.18, 0.66) to 0.56 (0.28, 0.78)
      in older children. Bivariate longitudinal analyses indicated modest to moderate
      genetic correlations across ages (r(A) varying from 0.34 to 0.58). Common genetic
      influences explained 17% to 43% of the phenotypic correlation between 2.5 and 9
      years for these appetite-related behaviors. In 9-year-old children, food
      acceptance traits, such as refusing to eat and being fussy about food, had high
      heritability estimates, 0.84 (0.63, 0.94) and 0.85 (0.59, 0.96) respectively,
      while in younger children, the shared environment (i.e., common to both twins)
      contributed most to phenotypic variance. Variances in meal-pattern-related
      behaviors were mostly explained by shared environmental influences. CONCLUSIONS:
      Genetic predispositions explain a large part of the variations in traits related
      to appetite during childhood, though our results suggest that as children get
      older, appetite-related behaviors become more sensitive to environmental
      influences outside the home. Still, for several traits environmental influences
      shared by twins appear to have the largest relative importance. This finding
      supports the notion that familial context has considerable potential to influence
      the development of healthy eating habits throughout childhood.

PMID- 24313978
TI  - Evaluation of infectious titer in a candidate HSV type 2 vaccine by a
      quantitative molecular approach.
AB  - BACKGROUND: One of the critical tasks in analytical testing is to monitor and
      assign the infectivity or potency of viral based vaccines from process
      development to production of final clinical lots. In this study, a high
      throughput RT-qPCR based approach was developed to evaluate the infectious titre
      in a replication-defective HSV-2 candidate vaccine, called HSV529. This assay is
      a combination of viral propagation and quantitative RT-PCR which measures the
      amount of RNA in infected cells after incubation with test samples. RESULTS: The
      relative infectious titre of HSV529 candidate vaccine was determined by a RT-qPCR
      method targeting HSV-2 gD2 gene. The data were analyzed using the parallel-line
      analysis as described in the European Pharmacopoeia 8th edition. The stability of
      HSV529 test samples were also investigated in a concordance study between RT-qPCR
      infectivity assay and a classical plaque assays. A suitable correlation was
      determined between both assays using an identical sample set in both assays. The
      RT-qPCR infectivity assay was further characterized by evaluating the
      intermediate precision and accuracy. The coefficient of variation from the six
      independent assays was less than 10%. The accuracy of each of the assay was also
      evaluated in the range of 92.91% to 120.57%. CONCLUSIONS: Our data demonstrate
      that the developed RT-qPCR infectivity assay is a rapid high throughput approach
      to quantify the infectious titer or potency of live attenuated or defective viral
      based vaccines, an attribute which is associated with product quality.

PMID- 24313979
TI  - Expression and prognostic significance of golgiglycoprotein73 (GP73) with
      epithelial-mesenchymal transition (EMT) related molecules in hepatocellular
      carcinoma (HCC).
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer and
      the third cause of cancer-related deaths, worldwide. It is essential to develop
      an effective prognostic biomarker and determine the mechanisms underlying HCC
      invasion and metastasis. AIMS: This study aimed to investigate the expression of
      Golgi glycoprotein73 (GP73) and Epithelial-mesenchymal transition (EMT) molecules
      such as E-cadherin and Vimentin in HCC. We also evaluated the prognostic value of
      GP73 in HCC. METHODS: Immunohistochemistry (IHC) was used to determine the
      expression of GP73 and EMT molecules in 75 HCC specimens and the corresponding
      paracarcinomatous liver (PCL) tissues. Spearman's correlation test was used to
      analyze the correlation of GP73 and EMT molecules. Clinicopathological features
      of the HCC patients were also analyzed. Univariate survival analysis was
      performed by the Kaplan-Meier method and differences among the groups were
      analyzed by the Log-rank test. RESULTS: GP73 expression in HCC was higher
      compared with PCL tissues (chi2 = 73.60, P < 0.05). EMT molecules were also
      detected in HCC and PCL tissues. GP73 was negatively correlated with E-cadherin
      (r = - 0.49, P < 0.05), but positively correlated with Vimentin (r = 0.46, P <
      0.05) in HCC. GP73 was correlated with the clinicopathological features including
      Edmondson grade, vascular invasion and TNM stage (P < 0.05), which was also
      associated with overall survival (OS) (P < 0.05). CONCLUSIONS: GP73 was
      negatively with E-cadherin and positively correlated with Vimentin. It might be
      associated with aggressive behavior of HCC and had influence on patients' OS.
      Further research is needed to determine the potential of GP73. VIRTUAL SLIDES:
      The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/29 vs/1504046946108618;
      http://med.motic.com/MoticGallery/Slide?id=3b6a037e-f60e-4c68-9106
      41e790de9431&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025;
      http://med.motic.com/MoticGallery/Slide?id=a25b5b32-b613-47b0-9f8b
      e1e67a95d1bf&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025.

PMID- 24313980
TI  - Clinical review: Ethics and end-of-life care for critically ill patients in
      China.
AB  - Critical care medicine in China has made great advances in recent decades. This
      has led to an unavoidable issue: end-of-life ethics. With advances in medical
      technology and therapeutics allowing the seemingly limitless maintenance of life,
      the exact time of death of an individual patient is often determined by the
      decision to limit life support. How to care for patients at the end of life is
      not only a medical problem but also a social, ethical, and legal issue. A lot of
      factors, besides culture, come into play in determining a person's ethical
      attitudes or behaviors, such as experience, education, religion, individual
      attributes, and economic considerations. Chinese doctors face ethical problems
      similar to those of their Western counterparts; however, since Chinese society is
      different from that of Western countries in cultural traditions, customs,
      religious beliefs, and ethnic backgrounds, there is a great difference between
      China and the Western world in regard to ethics at the end of life, and there is
      also a huge controversy within China. 

PMID- 24313981
TI  - Health examination utilization in the visually disabled population in Taiwan: a
      nationwide population-based study.
AB  - BACKGROUND: People with visual disabilities have increased health needs but face
      worse inequity to preventive health examinations. To date, only a few nationwide
      studies have analyzed the utilization of preventive adult health examinations by
      the visually disabled population. The aim of this study was to investigate the
      utilization of health examinations by the visually disabled population, and
      analyze the factors associated with the utilization. METHODS: Visual disability
      was certified by ophthalmologists and authenticated by the Ministry of the
      Interior (MOI), Taiwan. We linked data from three different nationwide datasets
      (from the MOI, Bureau of Health Promotion, and National Health Research
      Institutes) between 2006 and 2008 as the data sources. Independent variables
      included demographic characteristics, income status, health status, and severity
      of disability; health examination utilization status was the dependent variable.
      The chi-square test was used to check statistical differences between variables,
      and a multivariate logistic regression model was used to examine the associated
      factors with health examination utilization. RESULTS: In total, 47,812 visually
      disabled subjects aged 40 years and over were included in this study, only 16.6%
      of whom received a health examination. Lower utilization was more likely in male
      subjects, in those aged 65 years and above, insured dependents and those with a
      top-ranked premium-based salary, catastrophic illness/injury, chronic diseases of
      the genitourinary system, and severe or very severe disabilities. CONCLUSION: The
      overall health examination utilization in the visually disabled population was
      very low. Lower utilization occurred mainly in males, the elderly, and those with
      severe disabilities.

PMID- 24313982
TI  - Temporal lobe surgery in Germany from 1988 to 2008: diverse trends in etiological
      subgroups.
AB  - BACKGROUND AND PURPOSE: In the epilepsy community, there is talk that the number
      of classical patients with early onset temporal lobe epilepsy (TLE) and Ammon's
      horn sclerosis (AHS) is decreasing. This is counterintuitive, considering the
      success story of epilepsy surgery, improved diagnostic methods and the current
      recommendation of early admission to surgery. In order to recognize trends, the
      development of temporal lobe surgery over 20 years in three major German epilepsy
      centers was reviewed. METHODS: Age at surgery and duration of epilepsy, which was
      differentiated according to histopathology (AHS, developmental, tumor, vascular),
      year of surgery and center, were evaluated in a cohort of 2812 patients from
      three German epilepsy centers who underwent temporal lobe surgery between 1988
      and 2008. The analysis was carried out for the pooled cohort as well as for each
      center separately. RESULTS: Of all patients, 52% showed AHS. Compared with other
      pathologies, the AHS group had the earliest epilepsy onset and the longest
      duration of epilepsy. Across five time epochs, the diagnosis of AHS increased in
      the first epoch, remaining constant thereafter. Contrary to the trends in other
      pathologies, in the AHS group the mean age of patients at surgery increased by 7
      years and the duration of epilepsy until surgery increased by 5 years. This trend
      could be replicated in all three centers. As initially hypothesized for all
      groups, age and duration of epilepsy in other pathology groups remained constant
      or indicated earlier submission to surgery. CONCLUSIONS: During the first few
      years studied, most probably due to progress in brain imaging, the proportion of
      patients with AHS increased. However, despite stable numbers over time, and
      contrary to the trends in other pathology groups, age and duration of epilepsy in
      mesial TLE with AHS (mTLE + AHS) increased over time. This supports the
      hypothesis of a decreasing incidence of AHS. This trend is discussed with respect
      to disease-modifying factors which have changed the incidence of classical mTLE +
      AHS or, alternatively, to recent developments in antiepileptic drug treatment,
      the appraisal of surgery and economic incentives for treatment options other than
      surgery.

PMID- 24313983
TI  - Systematic study of cilostazol on secondary stroke prevention: a meta-analysis.
AB  - BACKGROUND: To study the efficacy and safety of cilostazol on ischemic stroke
      prevention and treatment, systematic reviews of related clinical randomized
      controlled trials were analyzed. METHODS: We searched the main databases for
      eligible trials including literature from January 1966 to November 2012 in
      MEDLINE, reports from 1980 to November 2012 in EMBASE, and all the studies
      published in EBSCO, Springer, Ovid, and Cochrane library citations. We also
      searched for keywords, including cilostazol and aspirin. RewMan 5.0 software was
      used to conduct the meta-analysis. RESULTS: Our search yielded five eligible
      trials. The effects of cilostazol and aspirin on ischemic stroke prevention and
      treatment were almost equal (combined odds ratio (OR) 0.78, 95% confidence
      interval (CI) (0.59, 1.04)). Additionally, both magnetic resonance angiography
      (MRA) and transcranial Doppler (TCD) examination showed that cilostazol could
      significantly decrease the incidence of intracranial artery stenosis exacerbation
      (MRA: combined OR 0.22, 95% CI (0.07, 0.68); TCD: combined OR 0.17, 95% CI (0.05,
      0.51)). In terms of adverse reactions, there were slightly fewer incidences of
      major bleeding with cilostazol than with aspirin (combined OR 0.38, 95% CI (0.24,
      0.60)), and there was no difference in the number of heart palpitations between
      cilostazol and aspirin. However, the incidence of gastrointestinal disorders,
      dizziness, and headaches caused by cilostazol was greater. CONCLUSIONS:
      Cilostazol might be a more effective and safer alternative to aspirin for
      patients with ischemic stroke. Further studies are required to confirm whether
      cilostazol is a suitable therapeutic option for secondary stroke prevention in
      larger cohorts of patients with ischemic stroke.

PMID- 24313985
TI  - Aromatic profile of ciders by chemical quantitative, gas chromatography
      olfactometry, and sensory analysis.
AB  - Nine samples of Asturias cider have been analyzed for volatile, olfactometric,
      and sensorial profiles. The aromatic composition was mainly constituted by fusel
      alcohols and ethyl esters. Among the minor volatile compounds, fatty acids,
      volatile phenols, and alcohols were the main components. The olfactometric
      analysis revealed the existence of 55 aromatic areas, exhibiting a wide range of
      intensities. Components like amyl alcohols, 2-phenylethanol, ethyl esters such as
      2-methylbutyrate, hexanoate and octanoate, hexanoic and octanoic acids 2
      phenylethyl acetate, 4-ethyl guaiacol, and 4-ethyl phenol could be considered as
      being part of the structure of cider aroma. The extract dilution analysis of one
      extract identified 2 volatile phenols (4-ethyl guaiacol and 4-ethyl phenol) among
      the most powerful odorants in cider. These components gave significant
      correlations with the sensory attributes sweet, spicy, and lees. 

PMID- 24313984
TI  - Prevalence of human papillomavirus in young Italian women with normal cytology:
      how should we adapt the national vaccination policy?
AB  - BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted
      infection. In Italy, HPV vaccination is now offered free of charge to 12-year-old
      females. However, some regional health authorities have extended free vaccination
      to other age-groups, especially to girls under 18 years of age. We conducted a
      multicentre epidemiological study to ascertain the prevalence of different
      genotypes of HPV in young Italian women with normal cytology, with the aim of
      evaluating the possibility of extending vaccination to older females. METHODS:
      The study was performed in 2010. Women aged 16-26 years with normal cytology were
      studied. Cervical samples were analyzed to identify the presence of HPV by PCR
      amplification of a segment of ORF L1 (450 bp). All positive HPV-DNA samples
      underwent viral genotype analysis by means of a restriction fragment length
      polymorphism assay. RESULTS: Positivity for at least one HPV genotype was found
      in 18.2% of the 566 women recruited: 48.1% in the 16-17 age-class, 15.4 in the 18
      20 age-class, 21.9% in the 21-23 age-class, and 15.5% in the 24-26 age-class;
      10.1% of women were infected by at least one high-risk HPV genotype. HPV-16 was
      the most prevalent genotype. Only 4 (0.7%), 4 (0.7%) and 3 (0.5%) women were
      infected by HPV-18, HPV-6 and HPV-11, respectively. Of the HPV-DNA-positive
      women, 64.1% presented only one viral genotype, while 24.3% had multiple
      infections. The HPV genotypes most often involved in multiple infections were
      high-risk. A high prevalence was noted in the first years of sexual activity
      (48.1% of HPV-DNA-positive women aged 16-17 years); HPV prevalence subsequently
      declined and stabilized.The estimate of cumulative proportions of young women
      free from any HPV infection at each age was evaluated; 93.3% and 97.1% of 26 year
      old women proved free from HPV-16 and/or HPV-18 and from HPV-6 and/or HPV-11,
      respectively. CONCLUSIONS: Our findings confirm the crucial importance of
      conducting studies on women without cytological damage, in order to optimise and
      up-date preventive interventions against HPV infection, and suggest that
      vaccinating 26-year-old females at the time of their first pap-test is to be
      recommend, though this issue should be further explored.

PMID- 24313987
TI  - Prevalence of latent tuberculosis infection in Sudan: a case-control study
      comparing interferon-gamma release assay and tuberculin skin test.
AB  - BACKGROUND: Most people exposed to M. tuberculosis show no evidence of clinical
      disease. Five to 10% of individuals with latent infection progress to develop
      overt disease during their life time. Identification of people with latent TB
      infection will increase case detection rates and may dictate new treatment
      policies to control tuberculosis. This study aimed to determine LTBI point
      prevalence in a population from Sudan using two different diagnostic methods: the
      tuberculin skin test (TST) and the IFN-gamma release assay (IGRA). METHODS: This
      was a prospective, community-based and case-controlled study. Following informed
      consent, household contacts (HHCs; n = 98) of smear-positive index cases and
      Community controls (CCs; 186), were enrolled. Tuberculin skin test (TST), whole
      blood stimulation with ESAT-6/CFP-10 +/- TB7.7 antigens or purified protein
      derivative (PPD) and IFN-gamma levels determination with ELISA were performed.
      The levels of IFN-gamma and TST induration between the CCs and the HHCs were
      compared using student t-test, Chi-square and Kappa coefficient. Pearson
      correlation test was used to compare TST and IFN-gamma. P levels of <0.05 were
      considered significant. RESULTS: TST induration of >= 10 mm gave an LTBI point
      prevalence of 327 cases/1000 individuals among HHCs compared to 126 cases/1000
      individuals among CCs (p = 0.000). PPD-induced IFN-gamma release assay gave an
      LTBI point prevalence of 418 cases/1000 individuals among HHCs compared to 301
      cases/1000 individuals among CCs (p =0.06). On the other hand ESAT-6/CFP-10 +/-
      TB7.7-induced IFN-gamma gave an LTBI point prevalence of 429 cases/1000
      individuals among HHCs compared to 268 cases/1000 individuals among CCs (p =
      0.01). IFN-gamma productions levels induced by ESAT-6/CPF-10 +/- TB7.7 antigens
      in HHCS and CCs were not significantly different from those induced by PPD (p =
      0.7). CONCLUSION: IFN-gamma release assay (IGRA) gave higher LTBI point
      prevalence compared to TST in HHCs and CCs. PPD gave comparable results to ESAT
      6/CFP-10 +/- TB7.7 antigens in whole blood IFN-gamma release, making it a cheap
      alternative to the recombinant antigens.

PMID- 24313986
TI  - Urinary biomarkers of kidney injury are associated with all-cause mortality in
      the Women's Interagency HIV Study (WIHS).
AB  - OBJECTIVES: Chronic kidney disease (CKD) is common in HIV-infected individuals,
      and is associated with mortality in both the HIV-infected and general
      populations. Urinary markers of tubular injury have been associated with future
      kidney disease risk, but associations with mortality are unknown. METHODS: We
      evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid
      binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase
      associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10
      year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to
      estimate the glomerular filtration rate (eGFRcys). RESULTS: There were 201 deaths
      during 9269 person-years of follow-up. After demographic adjustment, compared
      with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54;
      95% confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95% CI 1.44-2.89), NGAL
      (HR 1.50; 95% CI 1.05-2.14) and ACR (HR 1.63; 95% CI 1.13-2.36) were associated
      with higher mortality. After multivariable adjustment including adjustment for
      eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95% CI 1.29-2.74) and ACR
      (HR 1.46; 95% CI 1.01-2.12) remained independently associated with mortality.
      Findings for KIM-1 were borderline (HR 1.41; 95% CI 0.99-2.02). We found a J
      shaped association between L-FABP and mortality. Compared with persons in the
      lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95% CI 0.46
      0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP
      were simultaneously included in models. CONCLUSIONS: Among HIV-infected women,
      some urinary markers of tubular injury are associated with mortality risk,
      independently of eGFRcys and ACR. These markers represent potential tools with
      which to identify early kidney injury in persons with HIV infection.

PMID- 24313989
TI  - Invasive techniques for pain management in palliative care: a single center
      experience.
AB  - To achieve a successful pain control, interventional techniques are required in
      approximately 15% of the patients admitted to the Palliative Care Service (PCS).
      OBJECTIVES: To evaluate the frequency and effectiveness of the invasive
      procedures performed in the PCS of our health area. Other matters studied
      included complications associated with these procedures, the effects on morphine
      consumption, and functional status, survival rate, as well as the type and
      location of pain. METHODS: A descriptive, observational, retrospective study was
      performed between January 2009 and December 2011. Patients included were
      considered difficult to manage and required the assistance of the PCS of the
      University Hospital La Paz (Madrid). RESULTS: Patients were divided into 3 groups
      according to the technique used: sympathetic blocks (group S), epidural catheters
      (group C), and series of plexus, peripheral nerve, or epidural infiltrations
      (group I). Ninety-four procedures in 45 patients were performed (3.6% of patients
      admitted by the PCS). The average mean value of pain intensity before and after
      procedures decreased significantly (8.6 vs. 3.1, respectively, P < 0.01). The
      need for strong opioids was reduced (275.5 mg/day previously and 212.8 mg/day
      after the technique, P < 0.01). The overall complication rate was 16%.
      CONCLUSION: The analgesic efficacy of these techniques has been adequate in all
      groups. Patients who required epidural catheters had a higher rate of
      complications.

PMID- 24313990
TI  - Synchronous development of intrahepatic cholangiocarcinoma and hepatocellular
      carcinoma in different sites of the liver with chronic B-viral hepatitis: two
      case reports.
AB  - BACKGROUND: Synchronous development of primary hepatocellular carcinoma and
      intrahepatic cholangiocarcinoma has been reported rarely. In literature review,
      there have been only 35 reported cases of synchronous hepatocellular carcinoma
      and intrahepatic cholangiocarcinoma, and most of these tumors developed in
      patients with hepatitis C-related liver cirrhosis. Here, we present synchronous
      development of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in
      two patients with chronic B-viral hepatitis. CASE PRESENTATION: Two patients with
      chronic hepatitis B were referred to our hospital due to a hepatic mass. Patient
      1 had a 6.4 cm multinodular hepatic mass in the left lobe and a small nodule in
      the right lobe. Patient 2 had a 4.3 cm hypervascular mass in the right lobe and a
      1.1 cm nodule in the left lobe. The pre-operative diagnosis of both cases was
      hepatocellular carcinoma with metastatic nodule, however, surgical resection
      pathology revealed that hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma existed independently in the other side of the liver in both
      cases. Additionally, the background liver histology of both cases was hepatitis B
      related chronic hepatitis without cirrhotic change. CONCLUSION: Our cases suggest
      that hepatitis B virus infection can also predispose to development of double
      liver cancers.

PMID- 24313991
TI  - Genetic characterization of seasonal influenza A (H3N2) viruses in Ontario during
      2010-2011 influenza season: high prevalence of mutations at antigenic sites.
AB  - BACKGROUND: The direct effect of antigenic site mutations in influenza viruses on
      antigenic drift and vaccine effectiveness is poorly understood. OBJECTIVE: To
      investigate the genetic and antigenic characteristics of human influenza A (H3N2)
      viruses circulating in Ontario during the early 2010-2011 winter season. STUDY
      DESIGN: We sequenced the hemagglutinin (HA) and neuraminidase (NA) genes from 41
      A(H3N2) viruses detected in nasopharyngeal specimens. Strain typing was performed
      by hemagglutination inhibition (HI) assay. Molecular and phylogenetic tree
      analyses were conducted. RESULTS: HA and NA genes showed high similarity to the
      2010-2011 vaccine strain, A/Perth/16/2009 (H3N2)-like virus (97.7-98.5% and 98.7
      99.5% amino acid (AA) identity, respectively). Compared to A/Perth/16/2009
      strain, HA gene mutations were documented at 28 different AA positions across all
      five H3 antigenic sites, with a range of 5-11 mutations in individual viruses.
      Thirty-six (88%) viruses had 8 AA substitutions in common; none of these had
      reduced HI titer. Among Ontario isolates, 11 antigenic site AAs were positively
      selected with an increase in glycosylation sites. CONCLUSION: The presence of
      antigenic site mutations with high frequency among 2010-2011 influenza H3N2
      isolates confirms ongoing adaptive H3N2 evolution. These may represent early
      phylogenetic changes that could cause antigenic drift with further mutations.
      Clinical relevance of antigenic site mutations not causing drift in HI assays is
      unknown and requires further investigation. In addition, viral sequencing
      information will assist with vaccine strain planning and may facilitate early
      detection of vaccine escape.

PMID- 24313992
TI  - A systematic review of the psychological and social benefits of participation in
      sport for adults: informing development of a conceptual model of health through
      sport.
AB  - BACKGROUND: The definition of health incorporates the physical, social and mental
      domains, however the Physical Activity (PA) guidelines do not address social
      health. Furthermore, there is insufficient evidence about the levels or types of
      PA associated specifically with psychological health. This paper first presents
      the results of a systematic review of the psychological and social health
      benefits of participation in sport by adults. Secondly, the information arising
      from the systematic review has been used to develop a conceptual model of Health
      through Sport. METHODS: A systematic review of 14 electronic databases was
      conducted in June 2012, and studies published since 1990 were considered for
      inclusion. Studies that addressed mental and/or social health benefits from
      participation in sport were included. RESULTS: A total of 3668 publications were
      initially identified, of which 11 met the selection criteria. There were many
      different psychological and social health benefits reported, with the most
      commonly being wellbeing and reduced distress and stress. Sport may be associated
      with improved psychosocial health in addition to improvements attributable to
      participation in PA. Specifically, club-based or team-based sport seems to be
      associated with improved health outcomes compared to individual activities, due
      to the social nature of the participation. Notwithstanding this, individuals who
      prefer to participate in sport by themselves can still derive mental health
      benefits which can enhance the development of true-self-awareness and personal
      growth which is essential for social health. A conceptual model, Health through
      Sport, is proposed. The model depicts the relationship between psychological,
      psychosocial and social health domains, and their positive associations with
      sport participation, as reported in the literature. However, it is acknowledged
      that the capacity to determine the existence and direction of causal links
      between participation and health is limited by the cross-sectional nature of
      studies to date. CONCLUSION: It is recommended that participation in sport is
      advocated as a form of leisure-time PA for adults which can produce a range of
      health benefits. It is also recommended that the causal link between
      participation in sport and psycho-social health be further investigated and the
      conceptual model of Health through Sport tested.

PMID- 24313994
TI  - Multilocus variable-number tandem-repeat genotyping of Renibacterium
      salmoninarum, a bacterium causing bacterial kidney disease in salmonid fish.
AB  - BACKGROUND: Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum,
      is a bacterial disease of fish, which is both geographically widespread and
      difficult to control. Previously, application of various molecular typing methods
      has failed to reliably discriminate between R. salmoninarum isolates originating
      from different host species and geographic areas. The current study aimed to
      utilize multilocus variable number tandem repeats (VNTR) to investigate inter
      strain variation of R. salmoninarum to establish whether host-specific
      populations exist in Atlantic salmon and rainbow trout respectively. Such
      information would be valuable in risk assessment of transmission of R.
      salmoninarum in a multispecies aquaculture environment. RESULTS: The present
      analysis utilizing sixteen VNTRs distinguished 17 different haplotypes amongst 41
      R. salmoninarum isolates originating from Atlantic salmon and rainbow trout in
      Scotland, Norway and the US. The VNTR typing system revealed two well supported
      groups of R. salmoninarum haplotypes. The first group included R. salmoninarum
      isolates originating from both Atlantic salmon and rainbow trout circulating in
      Scottish and Norwegian aquaculture, in addition to the type strain ATCC33209T
      originating from Chinook salmon in North America. The second group comprised
      isolates found exclusively in Atlantic salmon, of mainly wild origin, including
      isolates NCIB1114 and NCIB1116 associated with the original Dee disease in
      Scotland. CONCLUSIONS: The present study confirmed that VNTR analysis can be
      successfully applied to discriminate R. salmoninarum strains. There was no clear
      distinction between isolates originating from Atlantic salmon and rainbow trout
      as several haplotypes in group 1 clustered together R. salmoninarum isolates from
      both species. These findings indicate a potential exchange of pathogens between
      Atlantic salmon and rainbow trout in Scottish and Norwegian aquaculture during
      the last 20 years. In a scenario of expansion of rainbow trout farming into the
      marine environment, appropriate biosecurity measures to minimize disease
      occurrence are advised. The present results also suggest that R. salmoninarum
      isolates circulating in European aquaculture over the last 20 years are
      genetically distant to the wild strains originally causing BKD in the rivers Dee
      and Spey.

PMID- 24313993
TI  - Galectin-3: its role in asthma and potential as an anti-inflammatory target.
AB  - Galectins constitute an evolutionary conserved family that bind to beta
      galactosides. Increasing evidence shows that galectins are involved in many
      fundamental biological processes such as cellular communication, inflammation,
      differentiation and apoptosis. Changes in galectin-3 (Gal-3) expression are
      commonly seen in cancer and pre-cancerous conditions, and Gal-3 may be involved
      in the regulation of diverse cancer cell activities that contribute to
      tumourigenesis, cancer progression and metastasis. In addition, Gal-3 is a pro
      inflammatory regulator in rheumatoid arthritis. Gal-3 has been shown to be
      involved in many aspects in allergic inflammation, such as eosinophil
      recruitment, airway remodeling, development of a Th2 phenotype as well as
      increased expression of inflammatory mediators. In an in vivo model it was shown
      that bronchoalveolar lavage (BAL) fluid from ovalbumin-challenged mice contained
      significantly higher levels of Gal-3 compared to control mice. The molecular
      mechanisms of Gal-3 in human asthma have not been fully elucidated. This review
      will focus on what is known about the Gal-3 and its role in the
      pathophysiological mechanisms of asthma to evaluate the potential of Gal-3 as a
      biomarker and therapeutic target of asthma. 

PMID- 24313995
TI  - Effects of a synbiotic on fecal quality, short-chain fatty acid concentrations,
      and the microbiome of healthy sled dogs.
AB  - BACKGROUND: Sled dogs commonly suffer from diarrhea. Although multiple etiologies
      exist there are limited field studies using synbiotics as a supplement to prevent
      or treat diarrhea. The objective of this study was to examine alterations in
      fecal quality, short-chain fatty acids (SCFA), and the fecal microbiome in two
      groups of training sled dogs fed a synbiotic or microcrystalline cellulose
      placebo. Twenty clinically healthy training sled dogs randomized into two cohorts
      (9 synbiotic-fed, 8 placebo-fed) for a 6 week prospective study were examined.
      Fecal pH and fecal short chain fatty acid (SCFA) concentrations were measured and
      tag-encoded FLX 16S rDNA amplicon pyrosequencing (bTEFAP) and quantitative real
      time PCR were performed at baseline (10 d prior to the study) and after 2 weeks
      of treatment with a total treatment time of 6 weeks. Fecal scores for all dogs
      were assessed at baseline and every day for 6 wk after initiation of treatment.
      RESULTS: Alterations in the fecal microbiome were observed with a significant
      rise in Lactobacillaceae in the synbiotic group (P = 0.004) after 2 wk of
      treatment. A positive correlation was found between Lactobacillaceae and overall
      butyrate concentration (R = 0.62, p = 0.011) in all dogs. After 5 wk of
      treatment, there was an improved fecal score and fewer days of diarrhea (Chi2 =
      5.482, P = 0.019) in the dogs given synbiotic, which coincided with a presumed
      contagious outbreak shared by all dogs in the study. CONCLUSIONS: Use of this
      synbiotic results in an increase in presumed beneficial bacterial flora of the
      host colon which was associated with a decrease in the prevalence of diarrhea in
      training sled dogs.

PMID- 24313997
TI  - Dysarthria plus dysphagia is associated with severe sleep-disordered breathing in
      patients with acute intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is a risk factor for
      stroke. The frequency of SDB in Japanese patients with acute intracerebral
      hemorrhage (ICH) was investigated, as well as factors associated with SDB
      severity. METHODS: Between April 2010 and April 2013, patients with ICH within 24
      h of onset were prospectively enrolled to participate in a sleep study within 7
      days of admission. SDB was defined as a respiratory disturbance index (RDI: apnea
      or hypopnea events per hour) of >= 5. Patients were assigned to groups based on
      RDI values of >= 30 (severe SDB) and <30 (absent or not severe SDB). The
      frequency of SDB and factors associated with its severity were investigated using
      multivariate logistic regression analysis. RESULTS: Of 97 patients (55 males;
      mean age 68.1 years) enrolled in the study, 91 (94%) had SDB. Severe SDB was
      evident in 29 (30%) patients. Compared with the RDI< 30 group, the RDI >= 30
      group had a higher frequency of dysarthria plus dysphagia (76% vs. 47%, P =
      0.008), larger waist circumference [86 (84-92) vs. 84 (78-88) cm, P = 0.019] and
      a greater body mass index [23.8 (21.1-26.8) vs. 21.5 (19.4-25.0) kg/m(2), P =
      0.046]. Multivariate logistic regression analysis showed that dysarthria plus
      dysphagia was independently associated with severe SDB (odds ratio 3.4; 95%
      confidence interval 1.250-9.252, P = 0.017). CONCLUSION: Most Japanese patients
      with acute ICH had SDB, and dysarthria plus dysphagia was associated with severe
      SDB.

PMID- 24313996
TI  - Fermentation stage-dependent adaptations of Bacillus licheniformis during enzyme
      production.
AB  - BACKGROUND: Industrial fermentations can generally be described as dynamic
      biotransformation processes in which microorganisms convert energy rich
      substrates into a desired product. The knowledge of active physiological
      pathways, reflected by corresponding gene activities, allows the identification
      of beneficial or disadvantageous performances of the microbial host. Whole
      transcriptome RNA-Seq is a powerful tool to accomplish in-depth quantification of
      these gene activities, since the low background noise and the absence of an upper
      limit of quantification allow the detection of transcripts with high dynamic
      ranges. Such data enable the identification of potential bottlenecks and futile
      energetic cycles, which in turn can lead to targets for rational approaches to
      productivity improvement. Here we present an overview of the dynamics of gene
      activity during an industrial-oriented fermentation process with Bacillus
      licheniformis, an important industrial enzyme producer. Thereby, valuable
      insights which help to understand the complex interactions during such processes
      are provided. RESULTS: Whole transcriptome RNA-Seq has been performed to study
      the gene expression at five selected growth stages of an industrial-oriented
      protease production process employing a germination deficient derivative of B.
      licheniformis DSM13. Since a significant amount of genes in Bacillus strains are
      regulated posttranscriptionally, the generated data have been confirmed by 2D gel
      based proteomics. Regulatory events affecting the coordinated activity of
      hundreds of genes have been analyzed. The data enabled the identification of
      genes involved in the adaptations to changing environmental conditions during the
      fermentation process. A special focus of the analyses was on genes contributing
      to central carbon metabolism, amino acid transport and metabolism, starvation and
      stress responses and protein secretion. Genes contributing to lantibiotics
      production and Tat-dependent protein secretion have been pointed out as potential
      optimization targets. CONCLUSIONS: The presented data give unprecedented insights
      into the complex adaptations of bacterial production strains to the changing
      physiological demands during an industrial-oriented fermentation. These are, to
      our knowledge, the first publicly available data that document quantifiable
      transcriptional responses of the commonly employed production strain B.
      licheniformis to changing conditions over the course of a typical fermentation
      process in such extensive depth.

PMID- 24313998
TI  - Epidemiological changes in meningococcal meningitis in Niger from 2008 to 2011
      and the impact of vaccination.
AB  - BACKGROUND: The epidemiology of bacterial meningitis in the African 'meningitis
      belt' changes periodically. In order to design an effective vaccination strategy,
      we have examined the epidemiological and microbiological patterns of bacterial
      meningitis, and especially that of meningococcal meningitis, in Niger during the
      period 2008-2011. During this period a mass vaccination campaign with the newly
      developed meningococcal A conjugate vaccine (MenAfriVac(r)) was undertaken.
      METHOD: Cerebrospinal fluid samples were collected from health facilities
      throughout Niger and analysed by culture, seroagglutination and/or speciation
      polymerase chain reaction, followed by genogrouping PCR for Neisseria
      meningitidis infections. A sample of strains were analysed by multi-locus
      sequence typing. RESULTS: N. meningitidis serogroup A cases were prevalent in
      2008 and 2009 [98.6% and 97.5% of all N. meningitidis cases respectively]. The
      prevalence of serogroup A declined in 2010 [26.4%], with the emergence of
      serogroup W Sequence Type (ST) 11 [72.2% of cases], and the serogroup A
      meningococcus finally disappeared in 2011. The geographical distribution of cases
      N. meningitidis serogroups A and W within Niger is described. CONCLUSION: The
      substantial decline of serogroup A cases that has been observed from 2010 onwards
      in Niger seems to be due to several factors including a major polysaccharide A/C
      vaccination campaign in 2009, the introduction of MenAfriVac(r) in 10 districts
      at risk in December 2010, the natural dynamics of meningococcal infection and the
      persistence of serogroup A sequence-type 7 for about 10 years. The emergence of
      serogroup W strains suggests that there may be a need for serogroup W containing
      vaccines in Niger in the coming years.

PMID- 24313999
TI  - Social media use by community-based organizations conducting health promotion: a
      content analysis.
AB  - BACKGROUND: Community-based organizations (CBOs) are critical channels for the
      delivery of health promotion programs. Much of their influence comes from the
      relationships they have with community members and other key stakeholders and
      they may be able to harness the power of social media tools to develop and
      maintain these relationships. There are limited data describing if and how CBOs
      are using social media. This study assesses the extent to which CBOs engaged in
      health promotion use popular social media channels, the types of content
      typically shared, and the extent to which the interactive aspects of social media
      tools are utilized. METHODS: We assessed the social media presence and patterns
      of usage of CBOs engaged in health promotion in Boston, Lawrence, and Worcester,
      Massachusetts. We coded content on three popular channels: Facebook, Twitter, and
      YouTube. We used content analysis techniques to quantitatively summarize posts,
      tweets, and videos on these channels, respectively. For each organization, we
      coded all content put forth by the CBO on the three channels in a 30-day window.
      Two coders were trained and conducted the coding. Data were collected between
      November 2011 and January 2012. RESULTS: A total of 166 organizations were
      included in our census. We found that 42% of organizations used at least one of
      the channels of interest. Across the three channels, organization promotion was
      the most common theme for content (66% of posts, 63% of tweets, and 93% of videos
      included this content). Most organizations updated Facebook and Twitter content
      at rates close to recommended frequencies. We found limited
      interaction/engagement with audience members. CONCLUSIONS: Much of the use of
      social media tools appeared to be uni-directional, a flow of information from the
      organization to the audience. By better leveraging opportunities for interaction
      and user engagement, these organizations can reap greater benefits from the non
      trivial investment required to use social media well. Future research should
      assess links between use patterns and organizational characteristics, staff
      perspectives, and audience engagement.

PMID- 24314000
TI  - Noninvasive ventilation and the upper airway: should we pay more attention?
AB  - In an effort to reduce the complications related to invasive ventilation, the use
      of noninvasive ventilation (NIV) has increased over the last years in patients
      with acute respiratory failure. However, failure rates for NIV remain high in
      specific patient categories. Several studies have identified factors that
      contribute to NIV failure, including low experience of the medical team and
      patient-ventilator asynchrony. An important difference between invasive
      ventilation and NIV is the role of the upper airway. During invasive ventilation
      the endotracheal tube bypasses the upper airway, but during NIV upper airway
      patency may play a role in the successful application of NIV. In response to
      positive pressure, upper airway patency may decrease and therefore impair minute
      ventilation. This paper aims to discuss the effect of positive pressure
      ventilation on upper airway patency and its possible clinical implications, and
      to stimulate research in this field. 

PMID- 24314001
TI  - A modified Delphi survey on the signs and symptoms of low back pain: indicators
      for an interventional management approach.
AB  - BACKGROUND: Low back pain (LBP) symptoms and signs are nonspecific. If required,
      diagnostic blocks may find the source of pain, but indicators of suspect
      diagnosis must be defined to identify anatomical targets. OBJECTIVE: To reach a
      consensus from an expert panel on the indicators for the most common causes of
      LBP. MATERIAL AND METHODS: A 3-round (2 telematic and 1 face-to-face) modified
      Delphi survey with a questionnaire on 78 evidence-based indicators of 7 LBP
      etiologies was completed by 23 experts. RESULTS: 98.7% of the questionnaire was
      consensuated. The most accepted indicators were for zygapophysial joint pain,
      painful ipsilateral paravertebral palpation, worsening with trunk extension,
      paravertebral musculature spasm on the affected articulation, and referred pain
      above the knee, without radicular pattern. For sacroiliac joint pain, unilateral
      pain when seating, with at least 3 described provoking tests: Approximation;
      gapping; Patrick's; Gaenslen's; thigh thrust; Fortin finger; and Gillet's tests.
      For discogenic pain, midline pain that may be provoked by pressure on the spinal
      processes at the affected level; for quadratus lumborum muscle, painful palpation
      on both the L1 level paravertebral region, referred to iliac crest, and the iliac
      crest, referred to greater trochanter. For iliopsoas muscle, pain elicited by
      thigh flexion, referred to buttock, inguinal region, and anterior thigh. For
      pyramidal muscle, pain while sitting on the affected side and positive Freiberg's
      test. For radicular pain, paresthesias and positive Lassegue's test at 60 degrees
      . CONCLUSION: Seventy-seven diagnostic suspect indicators of LBP conditions were
      consensuated. These may facilitate conservative or interventional pain management
      decision-making.

PMID- 24314002
TI  - Hereditary xerocytosis and familial haemolysis due to mutation in the PIEZO1
      gene: a simple diagnostic approach.

PMID- 24314003
TI  - CT-guided needle lung biopsy is possible during apneic oxygenation: a case
      series.
AB  - BACKGROUND: It can be difficult to perform CT guided biopsy of small pulmonary
      nodules especially if the position is behind a costa or close to the diaphragm
      and respiratory movements may hamper the procedure. During apneic oxygenation
      with a pulmonary standstill these movements can be hindered. METHODS: Six
      patients with decreased lung function and suspicious lung nodules are presented.
      Under general anesthesia including a muscle relaxant and a cuffed tube in the
      trachea CT guided biopsy was prepared. Just before the biopsy the ventilation
      mode was switched to a continuous positive airway pressure of 5-10 cm H2O,
      maintaining 100% oxygen delivery without ventilation. If the position of the lung
      nodule was inconvenient for biopsy the pressure was increased to up to 17 cm H2O
      to expand the lungs to a better biopsy position. After retrieving the biopsy
      controlled ventilation was re-established and a finishing control CT-scan was
      performed. Blood gas analyses were performed with few minutes interval. RESULTS:
      All biopsies were diagnostic. All patients survived the procedure with no major
      complications, but 3 patients developed pneumothorax. The length of apneic
      oxygenation was median 10 minutes (8-10 minutes). No major changes in vital
      parameters were observed, and in all patients the peripheral oxygen saturation
      was 100% throughout the procedure. The arterial oxygen tension rose to very high
      values and the lowest pH was 7.18. CONCLUSIONS: It is possible to perform lung
      biopsies in selected patients with decreased lung function during apneic
      oxygenation in at least 10 minutes in a safe way.

PMID- 24314004
TI  - Prevalence of and risk factors for pulmonary abnormalities in HIV-infected
      patients treated with antiretroviral therapy.
AB  - BACKGROUND: Pulmonary abnormalities are often present in patients infected with
      the human immunodeficiency virus (HIV). OBJECTIVES: The aim of the study was to
      determine the prevalence and characteristics of, and risk factors for, pulmonary
      abnormalities in HIV-positive patients. METHODS: A total of 275 HIV-positive
      patients [mean (+/- standard deviation) age 48.5 +/- 6.6 years] were included in
      the study, of whom 95.6% had been receiving highly active antiretroviral therapy
      (HAART) for a mean (+/- standard deviation) duration of 11.9 +/- 5.4 years. The
      median (interquartile range) CD4 lymphocyte count was 541 (392-813) cells/MUL,
      and 92% of the patients had an undetectable viral load. We determined: (1)
      spirometry, static lung volumes, lung diffusing capacity, pulmonary gas exchange
      and exercise tolerance, and (2) the amount of emphysema via a computed tomography
      (CT) scan. RESULTS: Chronic cough and expectoration (47%) and breathlessness
      during exercise (33.9%) were commonly reported. Airflow limitation (AL) was
      present in 17.2%, low pulmonary diffusing capacity in 52.2% and emphysema in 10.5
      37.7% of patients, depending on the method used for quantification. Most of these
      abnormalities had not been diagnosed or treated previously. Smoking exposure and
      previous tuberculosis were the main risk factors for AL, whereas smoking exposure
      and several variables related to HIV infection appeared to contribute to the risk
      of emphysema and low diffusing capacity. CONCLUSIONS: Despite HAART, pulmonary
      structural and functional abnormalities are frequent in HIV-positive patients.
      They are probably attributable to both environmental (smoking and tuberculosis)
      and HIV-related factors. Most of these abnormalities remain unnoticed and
      untreated. Given the relatively young age of these patients, these results
      anticipate a significant health problem in the next few years as, thanks to the
      efficacy of HAART, patients survive longer and experience the effects of aging.

PMID- 24314005
TI  - The dynamics of pyrethroid resistance in Anopheles arabiensis from Zanzibar and
      an assessment of the underlying genetic basis.
AB  - BACKGROUND: The emergence of pyrethroid resistance in the malaria vector,
      Anopheles arabiensis, threatens to undermine the considerable gains made towards
      eliminating malaria on Zanzibar. Previously, resistance was restricted to the
      island of Pemba while mosquitoes from Unguja, the larger of the two islands of
      Zanzibar, were susceptible. Here, we characterised the mechanism(s) responsible
      for resistance on Zanzibar using a combination of gene expression and target-site
      mutation assays. METHODS: WHO resistance bioassays were conducted using 1-5d old
      adult Anopheles gambiae s.l. collected between 2011 and 2013 across the
      archipelago. Synergist assays with the P450 inhibitor piperonyl-butoxide were
      performed in 2013. Members of the An. gambiae complex were PCR-identified and
      screened for target-site mutations (kdr and Ace-1). Gene expression in pyrethroid
      resistant An. arabiensis from Pemba was analysed using whole-genome microarrays.
      RESULTS: Pyrethroid resistance is now present across the entire Zanzibar
      archipelago. Survival to the pyrethroid lambda-cyhalothrin in bioassays conducted
      in 2013 was 23.5-54.3% on Unguja and 32.9-81.7% on Pemba. We present evidence
      that resistance is mediated, in part at least, by elevated P450 monoxygenases.
      Whole-genome microarray scans showed that the most enriched gene terms in
      resistant An. arabiensis from Pemba were associated with P450 activity and
      synergist assays with PBO completely restored susceptibility to pyrethroids in
      both islands. CYP4G16 was the most consistently over-expressed gene in resistant
      mosquitoes compared with two susceptible strains from Unguja and Dar es Salaam.
      Expression of this P450 is enriched in the abdomen and it is thought to play a
      role in hydrocarbon synthesis. Microarray and qPCR detected several additional
      genes putatively involved in this pathway enriched in the Pemba pyrethroid
      resistant population and we hypothesise that resistance may be, in part, related
      to alterations in the structure of the mosquito cuticle. None of the kdr target
      site mutations, associated with pyrethroid/DDT resistance in An. gambiae
      elsewhere in Africa, were found on the islands. CONCLUSION: The consequences of
      this resistance phenotype are discussed in relation to future vector control
      strategies on Zanzibar to support the ongoing malaria elimination efforts on the
      islands.

PMID- 24314006
TI  - Estimating the costs of implementing the rotavirus vaccine in the national
      immunisation programme: the case of Malawi.
AB  - OBJECTIVES: Worldwide, rotavirus infections cause approximately 453,000 child
      deaths annually. Two licensed vaccines could be life- and cost-saving in low
      income countries where the disease burden is highest. The aim of our study was to
      estimate the total cost of implementing the rotavirus vaccine in the national
      immunisation programme of a low-income country. Furthermore, the aim was to
      examine the relative contribution of different components to the total cost.
      METHODS: Following the World Health Organization guidelines, we estimated the
      resource use and costs associated with rotavirus vaccine implementation, using
      Malawi as a case. The cost analysis was undertaken from a governmental
      perspective. All costs were calculated for a 5-years period (2012-2016) and
      discounted at 5%. The value of key input parameters was varied in a sensitivity
      analysis. RESULTS: The total cost of rotavirus vaccine implementation in Malawi
      amounted to US$ 18.5 million over a 5-years period. This translated into US$ 5.8
      per child in the birth cohort. With GAVI Alliance financial support, the total
      cost was reduced to US$ 1.4 per child in the birth cohort. Approximately 83% of
      the total cost was attributed to vaccine purchase, while 17% was attributed to
      system costs, with personnel, transportation and cold chain as the main cost
      components. CONCLUSION: The total cost of rotavirus vaccine implementation in
      Malawi is high compared with the governmental health budget of US$ 26 per capita
      per year. This highlights the need for new financing opportunities for low-income
      countries to facilitate vaccine implementation and ensure sustainable financing.

PMID- 24314007
TI  - An epidemiological investigation into the association between biomarkers and
      growth performance in nursery pigs.
AB  - BACKGROUND: Biomarkers are useful tools in research and clinical practice where
      they are often used to detect and monitor differences in the physiological state
      of an animal. The proteins IGF-1, IGFBP-3, GHR, CRP, SAA, Hp, IFN-alpha, IFN
      gamma, TNF-alpha, IL-1beta, IL-6, IL-10, and IL-18 have been proposed as
      potential biomarkers for monitoring growth in livestock. The objective of this
      study was to determine whether hepatic gene expression of these proposed
      biomarkers is associated with growth performance in nursery pigs. Herd
      information and growth parameters were collected for 168 piglets from 8
      commercial farms in southern Ontario. From these pigs, a subset of liver tissue
      samples (n = 74) was used for gene expression analysis of the proposed
      biomarkers. Multivariable linear regression methods were used to determine
      whether genetic expression of the proposed biomarkers was associated with growth
      performance in the nursery. RESULTS: Modelling the herd information and
      individual piglet traits in relation to growth performance revealed that the
      weight at weaning and the age at weaning are significantly associated with
      nursery performance. Average daily gain (ADG) was significantly associated with
      hepatic IGFBP-3 and GHR expression in the liver (P < 0.05), and tended to be
      associated with hepatic IGF-1 expression (P = 0.071). Similarly, 9-week body
      weight was significantly associated with hepatic expression of IGFBP-3 and GHR
      expression (P < 0.05), and tended to be associated with hepatic expression of IGF
      1 (P = 0.055). CONCLUSION: The age and weight at which pigs are weaned is an
      important determinant for nursery performance. Hepatic gene expression of IGF-1,
      IGFBP-3, and GHR can be useful biomarkers for monitoring growth performance in
      nursery pigs.

PMID- 24314008
TI  - Trends in influenza vaccination coverage in Portugal from 1998 to 2010: effect of
      major pandemic threats.
AB  - BACKGROUND: Vaccination is the key measure available for prevention of the public
      health burden of annual influenza epidemics. This article describes national
      trends in seasonal influenza vaccine (IV) coverage in Portugal from 1998/99 to
      2010/11, analyzes progress towards meeting WHO 2010 coverage goals, and addresses
      the effect of major public health threats of the last 12 years (SARS in 2003/04,
      influenza A (H5N1) in 2005/06, and the influenza A (H1N1)2009 pandemic) on
      vaccination trends. METHODS: The National Institute of Health surveyed (12 times)
      a random sample of Portuguese families. IV coverage was estimated and was
      adjusted for age distribution and country region. Independence of age and sex
      coverage distribution was tested using a modified F-statistic with a 5%
      significance level. The effect of SARS, A (H5N1), and the A (H1N1)2009 pandemic
      was tested using a meta-regression model. The model was adjusted for IV coverage
      in the general population and in the age groups. RESULTS: Between 1998/99 and
      2010/11 IV, coverage in the general population varied between 14.2% (CI(95%):
      11.6%-16.8%) and 17.5% (CI(95%): 17.6%-21.6%). There was no trend in coverage (p
      = 0.097). In the younger age group (<15 years) a declining trend was identified
      until 2008/09 (p = 0.005). This trend reversed in 2009/10. There was also a
      gradual and significant increase in seasonal IV coverage in the elderly (p for
      trend < 0.001). After 2006/07, IV coverage remained near 50%. Adjusting for
      baseline trends, there was significantly higher coverage in the general
      population in 2003/04 (p = 0.032) and 2005/06 (p = 0.018). The high coverage
      observed in the <15-year age group in season 2009/10 was also significant (p =
      0.015). CONCLUSIONS: IV coverage in the elderly population displayed an
      increasing trend, but the 75% WHO 2010 target was not met. This result indicates
      that influenza vaccination strategy should be improved to meet the ambitious WHO
      coverage goals. The major pandemic threats of the past decade had a modest but
      significant effect on seasonal influenza vaccination. There was an increase in
      vaccine uptake proportion in the general population in 2003/04 and in 2005/06,
      and in individuals <15 years old in 2009/10.

PMID- 24314009
TI  - The mononuclear metal center of type-I dihydroorotase from Aquifex aeolicus.
AB  - BACKGROUND: Dihydroorotase (DHO) is a zinc metalloenzyme, although the number of
      active site zinc ions has been controversial. E. coli DHO was initially thought
      to have a mononuclear metal center, but the subsequent X-ray structure clearly
      showed two zinc ions, alpha and beta, at the catalytic site. Aquifex aeolicus
      DHO, is a dodecamer comprised of six DHO and six aspartate transcarbamoylase
      (ATC) subunits. The isolated DHO monomer, which lacks catalytic activity, has an
      intact alpha-site and conserved beta-site ligands, but the geometry of the second
      metal binding site is completely disrupted. However, the putative beta-site is
      restored when the complex with ATC is formed and DHO activity is regained.
      Nevertheless, the X-ray structure of the complex revealed a single zinc ion at
      the active site. The structure of DHO from the pathogenic organism, S. aureus
      showed that it also has a single active site metal ion. RESULTS: Zinc analysis
      showed that the enzyme has one zinc/DHO subunit and the addition of excess metal
      ion did not stimulate catalytic activity, nor alter the kinetic parameters. The
      metal free apoenzyme was inactive, but the full activity was restored upon the
      addition of one equivalent of Zn2+ or Co2+. Moreover, deletion of the beta-site
      by replacing the His180 and His232 with alanine had no effect on catalysis in the
      presence or absence of excess zinc. The 2.2 A structure of the double mutant
      confirmed that the beta-site was eliminated but that the active site remained
      otherwise intact. CONCLUSIONS: Thus, kinetically competent A. aeolicus DHO has a
      mononuclear metal center. In contrast, elimination of the putative second metal
      binding site in amidohydrolyases with a binuclear metal center, resulted in the
      abolition of catalytic activity. The number of active site metal ions may be a
      consideration in the design of inhibitors that selectively target either the
      mononuclear or binuclear enzymes.

PMID- 24314011
TI  - Fusion of Hsp70 to Mage-a1 enhances the potency of vaccine-specific immune
      responses.
AB  - BACKGROUND: Heat shock proteins (HSPs) are capable of promoting antigen
      presentation of chaperoned peptides through interactions with receptors on
      antigen presenting cells. This property of HSPs suggests a potential function as
      an adjuvant-free carrier to stimulate immune responses against a covalently
      linked fusion partner. MAGE-A1 is a likely candidate for tumor immunotherapy due
      to its abundant immunogenic epitopes and strict tumor specificity. To analyze the
      influence of HSP70 conjugation to MAGE-A1, towards developing a novel effective
      vaccine against MAGE-expressing tumors, we cloned the murine counterpart of the
      human HSP70 and MAGE-A1 genes. METHODS: Recombinant proteins expressing Mage-a1
      (aa 118-219), Hsp70, and Mage-a1-Hsp70 fusion were purified and used to immunize
      C57BL/6 mice. The humoral and cellular responses elicited against Mage-a1 were
      measured by ELISA, IFN-gamma ELISPOT assay, and cytotoxicity assay. RESULTS:
      Immunization of mice with Mage-a1-Hsp70 fusion protein elicited significantly
      higher Mage-a1-specific antibody titers than immunization with either Mage-a1
      alone or a combination of Mage-a1+Hsp70. The frequency of IFN-gamma-producing
      cells and the cytotoxic T lymphocyte (CTL) activity was also elevated. Consistent
      with the elevated immune response, immunization with fusion protein induced
      potent in vivo antitumor immunity against MAGE-a1-expressing tumors. CONCLUSIONS:
      These results indicate that the fusion of Hsp70 to Mage-a1 can enhance immune
      responses and anti-tumor effects against Mage-a1-expressing tumors. Fusion of
      HSP70 to a tumor antigen may greatly enhance the potency of protein vaccines and
      can potentially be applied to other cancer systems with known tumor-specific
      antigens. These findings provide a scientific basis for the development of a
      novel HSP70 and MAGE fusion protein vaccine against MAGE-expressing tumors.

PMID- 24314010
TI  - Plasticity in neuromagnetic cortical responses suggests enhanced auditory object
      representation.
AB  - BACKGROUND: Auditory perceptual learning persistently modifies neural networks in
      the central nervous system. Central auditory processing comprises a hierarchy of
      sound analysis and integration, which transforms an acoustical signal into a
      meaningful object for perception. Based on latencies and source locations of
      auditory evoked responses, we investigated which stage of central processing
      undergoes neuroplastic changes when gaining auditory experience during passive
      listening and active perceptual training. Young healthy volunteers participated
      in a five-day training program to identify two pre-voiced versions of the stop
      consonant syllable 'ba', which is an unusual speech sound to English listeners.
      Magnetoencephalographic (MEG) brain responses were recorded during two pre
      training and one post-training sessions. Underlying cortical sources were
      localized, and the temporal dynamics of auditory evoked responses were analyzed.
      RESULTS: After both passive listening and active training, the amplitude of the
      P2m wave with latency of 200 ms increased considerably. By this latency, the
      integration of stimulus features into an auditory object for further conscious
      perception is considered to be complete. Therefore the P2m changes were discussed
      in the light of auditory object representation. Moreover, P2m sources were
      localized in anterior auditory association cortex, which is part of the antero
      ventral pathway for object identification. The amplitude of the earlier N1m wave,
      which is related to processing of sensory information, did not change over the
      time course of the study. CONCLUSION: The P2m amplitude increase and its
      persistence over time constitute a neuroplastic change. The P2m gain likely
      reflects enhanced object representation after stimulus experience and training,
      which enables listeners to improve their ability for scrutinizing fine
      differences in pre-voicing time. Different trajectories of brain and behaviour
      changes suggest that the preceding effect of a P2m increase relates to brain
      processes, which are necessary precursors of perceptual learning. Cautious
      discussion is required when interpreting the finding of a P2 amplitude increase
      between recordings before and after training and learning.

PMID- 24314012
TI  - Effects of thoracic epidural anesthesia on survival and microcirculation in
      severe acute pancreatitis: a randomized experimental trial.
AB  - INTRODUCTION: Severe acute pancreatitis is still a potentially life threatening
      disease with high mortality. The aim of this study was to evaluate the
      therapeutic effect of thoracic epidural anaesthesia (TEA) on survival,
      microcirculation, tissue oxygenation and histopathologic damage in an
      experimental animal model of severe acute pancreatitis in a prospective animal
      study. METHODS: In this study, 34 pigs were randomly assigned into 2 treatment
      groups. After severe acute pancreatitis was induced by intraductal injection of
      glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2
      ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA
      was applied. During a period of 6 hours after induction, tissue oxygen tension
      (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter
      animals were observed for 7 days followed by sacrification and histopathologic
      examination. RESULTS: Survival rate after 7 days was 82% in Group 1 (TEA) versus
      29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly
      superior microcirculation (1,608 +/- 374 AU versus 1,121 +/- 510 AU; P <0.05) and
      tissue oxygenation (215 +/- 64 mmHg versus 138 +/- 90 mmHG; P <0.05) as compared
      to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the
      histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05).
      CONCLUSIONS: TEA led to improved survival, enhanced microcirculatory perfusion
      and tissue oxygenation and resulted in less histopathologic tissue-damage in an
      experimental animal model of severe acute pancreatitis.

PMID- 24314013
TI  - Genetic dissection of the polyoxin building block-carbamoylpolyoxamic acid
      biosynthesis revealing the "pathway redundancy" in metabolic networks.
AB  - BACKGROUND: Polyoxin, a peptidyl nucleoside antibiotic, consists of three
      building blocks including a nucleoside skeleton, polyoximic acid (POIA), and
      carbamoylpolyoxamic acid (CPOAA), however, little is known about the "pathway
      redundancy" of the metabolic networks directing the CPOAA biosynthesis in the
      cell factories of the polyoxin producer. RESULTS: Here we report the genetic
      characterization of CPOAA biosynthesis with revealing a "pathway redundancy" in
      metabolic networks. Independent mutation of the four genes (polL-N and polP)
      directly resulted in the accumulation of polyoxin I, suggesting their positive
      roles for CPOAA biosynthesis. Moreover, the individual mutant of polN and polP
      also partially retains polyoxin production, suggesting the existence of the
      alternative homologs substituting their functional roles. CONCLUSIONS: It is
      unveiled that argA and argB in L-arginine biosynthetic pathway contributed to the
      "pathway redundancy", more interestingly, argB in S. cacaoi is indispensible for
      both polyoxin production and L-arginine biosynthesis. These data should provide
      an example for the research on the "pathway redundancy" in metabolic networks,
      and lay a solid foundation for targeted enhancement of polyoxin production with
      synthetic biology strategies.

PMID- 24314014
TI  - Bilateral brachial plexus injury following acute carbon monoxide poisoning.
AB  - BACKGROUND: Carbon monoxide (CO) intoxication is a leading cause of severe
      neuropsychological impairments. Peripheral nerve injury has rarely been reported.
      It consists usually in a demyelinating polyneuropathy or mononeuropathy affecting
      mainly the lower limbs. Isolated involvement of both upper extremities has been
      described in only 4 patients related to root damage. We report the first case of
      bilateral brachial plexus injury following CO poisoning and review all previous
      CO-induced neuropathy described in literature. CASE PRESENTATION: After being
      unconscious for three hours, a 42 years old man experienced bilateral brachial
      weakness associated with edema of the face and the upper limbs. Neurological
      examination showed a brachial diplegia, distal vibratory, thermic and algic
      hypoesthesia, deep tendon areflexia in upper limbs. There was no sensory or motor
      deficit in lower extremities. No cognitive disturbances were detected. Creatine
      kinase was elevated. Electroneuromyogram patterns were compatible with the
      diagnosis of bilateral C5 D1 brachial axonal plexus injury predominant on the
      left side. Clinical course after hyperbaric oxygen therapy was marked by a
      complete recovery of neurological disorders. CONCLUSION: Peripheral neuropathy is
      an unusual complication of CO intoxication. Bilateral brachial plexus impairment
      is exceptional. Various mechanisms have been implicated including nerve
      compression secondary to rhabdomyolysis, nerve ischemia due to hypoxia and direct
      nerve toxicity of carbon monoxide. Prognosis is commonly excellent without any
      sequelae.

PMID- 24314015
TI  - Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone
      turnover markers in HIV-infected patients.
AB  - BACKGROUND: Osteoporosis and bone fractures seem to be higher in HIV-infected
      Patients compared to the general populations. Moreover, bone turnover markers are
      increased in patients on antiretroviral therapy and vitamin D deficiency is
      prevalent in HIV-infected patients. However, the influence of per oral
      cholecalciferol on bone metabolism in HIV infected patients is not well
      understood. METHODS: We measured the bone turnover markers in 96 HIV-infected
      patients: Bone specific alkaline phosphatase (BSAP), Pyridinoline (PYR),
      Desoxypyridinoline (DPD) and 25-OH vitamin D. If 25-OH vitamin D was below 75
      nnol/L (87/96 patients), 300000 IU cholecalciferol was given per os. 25OH-vitamin
      D and bone turn over markers were determinded 3 month later. 25 OH-vitamin D was
      corrected for circannual rythm y'=y+17.875*sin2pi/365*day+2.06, whereas bone
      turnover markers were not corrected. The paired students t-Test was used to
      compare the two periods. No calcium supplementation or biphosphonate therapy was
      given. RESULTS: Corrected 25OH-vitamin D levels increased significantly after
      supplementation (42.7 +/- 26.61 vs. 52.85 +/- 21.8 nmol/L, p < 0.001). After
      supplementation, bone turnover markers were significantly lower. The values
      decreased for BSAP from 21.31 +/- 14.32 to 17.53 +/- 8.17 MUg/L (p < 0.001), PYR
      from 74.57 +/- 36.83 to 54.82 +/- 21.43 nmol/mmol creatinine (p < 0.001) and DPD
      from 15.17 +/- 8.34 to 12.61 +/- 5.02 nmol/mmol creatinine (p = 0.01).
      CONCLUSIONS: After per oral substitution with cholecalciferol, bone formation as
      well as bone resorption markers decreased significant. We postulate a protective
      effect on bone structure with cholecalciferol supplementation.

PMID- 24314016
TI  - Oral prophylaxis and its effects on halitosis-associated and inflammatory
      parameters in patients with chronic periodontitis.
AB  - OBJECTIVE: A controlled clinical trial was conducted to evaluate the effects of
      oral prophylaxis on halitosis-associated, immunological and microbiological
      parameters. METHODS: Thirty subjects were included in this controlled clinical
      trial (patients with generalized chronic periodontitis and controls without
      clinical attachment loss; each n = 15). Before oral prophylaxis and 14 days after
      (including tongue cleaning) volatile sulphur compounds (VSC), organoleptic scores
      and a tongue coating index were evaluated. The levels of IL-1beta, IL-8, IL-10
      and MMP-8 were measured in GCF, and also major periodontal pathogens were
      detected. Data were statistically analysed using anova and paired t-test.
      RESULTS: Supragingival plaque and calculus removal with combined tongue cleaning
      was able to reduce significantly (P < 0.05) the VSC values in both groups (no
      significant differences between both groups). Two weeks after periodontal
      debridement, the VSC values were observed in the periodontitis group, but not in
      the control group, similar to the baseline values. The difference between the
      groups was statistically significant (P < 0.05). Only a repeated prophylaxis
      session in the periodontitis group was able to reduce VSC values significantly in
      comparison with baseline (P < 0.05). Organoleptic scores (10 and 30 cm) were
      significantly different (P < 0.05) between both groups before and after the
      treatment. Periodontal pathogens and host-derived markers were not significantly
      affected by a single prophylaxis session. CONCLUSIONS: Oral prophylaxis may
      result in a significant decrease in VSC values. However, in periodontal diseases,
      a more complex treatment seems to be necessary.

PMID- 24314017
TI  - A meta-analysis of the efficacy and safety of unboosted atazanavir compared with
      ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults
      with established virological suppression after induction.
AB  - OBJECTIVES: Treatment simplification involving induction with a ritonavir (RTV)
      boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has
      been shown to be a viable option for long-term antiretroviral therapy. To
      evaluate the clinical evidence for this approach, we conducted a systematic
      review and meta-analysis of randomized controlled trials (RCTs) evaluating
      efficacy and safety in patients with established virological suppression.
      METHODS: Several databases were searched without limits on time or language.
      Searches of conferences were also conducted. RCTs were included if they compared
      a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta
      analysis was conducted using a random effects model for the proportion achieving
      virological suppression (i.e. HIV RNA < 50 and <400 HIV-1 RNA copies/mL), CD4
      cell counts, lipid levels and liver function tests. Dichotomous outcomes were
      reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs).
      RESULTS: Five studies (n = 1249) met the inclusion criteria. The meta-analysis
      demonstrated no statistically significant difference in efficacy (i.e. HIV RNA <
      50 copies/mL) between PI/RTV and unboosted atazanavir [RR = 1.04; 95% confidence
      interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a
      subanalysis of studies where atazanavir/RTV was the only PI/RTV used during
      induction. Additional efficacy results support these findings. A significant
      reduction in total cholesterol (P < 0.00001), triglycerides (P = 0.0002), low
      density lipoprotein (LDL) cholesterol (P = 0.009) and hyperbilirubinaemia (P =
      0.02) was observed with unboosted atazanavir vs. PI/RTV. CONCLUSIONS: The meta
      analysis demonstrated that switching patients with virological suppression from
      an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e.
      blood parameter abnormalities) without sacrificing virological efficacy.

PMID- 24314018
TI  - Crawling and walking infants elicit different verbal responses from mothers.
AB  - We examined mothers' verbal responses to their crawling or walking infants'
      object sharing (i.e. bids). Fifty mothers and their 13-month-olds were observed
      for 1 hour at home. Infants bid from a stationary position or they bid after
      carrying the object to their mothers. Mothers responded with affirmations (e.g.
      'thank you'), descriptions ('red box'), or action directives ('open it').
      Infants' locomotor status and the form of their bids predicted how mothers
      responded. Mothers of walkers responded with action directives more often than
      mothers of crawlers. Notably, differences in the responses of mothers of walkers
      versus those of crawlers were explained by differences in bid form between the
      two groups of infants. Walkers were more likely to engage in moving bids than
      crawlers, who typically shared objects from stationary positions. When crawlers
      displayed moving bids, their mothers offered action directives just as often as
      did mothers of walkers. Findings illustrate developmental cascades, wherein
      Infants' locomotor status affects how infants share objects with mothers, which
      in turn shapes mothers' verbal responses. 

PMID- 24314020
TI  - Parental alcohol misuse and hazardous drinking among offspring in a general
      teenage population: gender-specific findings from the Young-HUNT 3 study.
AB  - BACKGROUND: Parental alcohol misuse may negatively affect drinking behaviours
      among offspring, but it is unclear to what extent influences are gender-specific
      and dependent upon the actual drinking behaviour measured. The aim of this study
      was to investigate whether hazardous drinking among Norwegian teenage boys (N =
      2538) and girls (N = 2494) was associated with paternal and maternal alcohol
      misuse (CAGE). METHODS: Definitions of hazardous drinking among offspring were
      based on self-reported alcohol consumption (in litres a year), frequency of
      drinking, and frequency of drunkenness. Based on this information, two composite
      measures of hazardous drinking were also constructed. Cross-sectional data from
      the Norwegian Young-HUNT 3 survey (2006-2008) were linked to information from
      biological parents who participated in the adult part of the HUNT study. RESULTS:
      Logistic regression analyses showed that both boys and girls with alcohol
      misusing fathers were more likely to report high levels of alcohol intake
      compared to others of the same age and gender. This was contrary to boys with
      misusing mothers, who reported less alcohol consumption than other boys. Among
      girls, but not boys, high frequency of drunkenness was associated with maternal
      as well as paternal misuse. CONCLUSIONS: This study suggests that adolescent
      hazardous drinking is more prevalent among boys and girls with alcohol misusing
      parents versus those whose parents do not misuse alcohol. However, findings were
      gender specific and varied depending on the drinking outcomes under
      investigation. More evidence-based knowledge in this field is of great importance
      for better understanding the possible role paternal and maternal alcohol misuse
      may play in the development of hazardous alcohol drinking patterns among
      adolescent boys and girls.

PMID- 24314019
TI  - Fact or fiction--identifying the elusive multiple myeloma stem cell.
AB  - Multiple myeloma (MM) is a debilitating disease of proliferating and malignant
      plasma cells that is currently incurable. The ability of monoclonal recurrence of
      disease suggests it might arise from a stem cell-like population capable of self
      renewal. The difficulty to isolate the cancer stem-like cell in MM has introduced
      confusion toward this hypothesis. However, recent evidence has suggested that MM
      originates from the B cell lineage with memory-B cell like features, allowing for
      self-renewal of the progenitor-like status and differentiation to a monoclonal
      plasma cell population. Furthermore, this tumor-initiating cell uses signaling
      pathways and microenvironment similar to the hematopoietic stem cell, though
      hijacking these mechanisms to create and favor a more tumorigenic environment.
      The bone marrow niche allows for pertinent evasion, either through avoiding
      immunosurveillance or through direct interaction with the stroma, inducing
      quiescence and thus drug resistance. Understanding the interaction of the MM stem
      cell to the microenvironment and the mechanisms utilized by various stem cell
      like populations to allow persistence and therapy-resistance can enable for
      better targeting of this cell population and potential eradication of the
      disease.

PMID- 24314021
TI  - Molecular characterization of vernalization and response genes in bread wheat
      from the Yellow and Huai Valley of China.
AB  - BACKGROUND: Flowering time greatly influences the adaptation of wheat cultivars
      to diverse environmental conditions and is mainly controlled by vernalization and
      photoperiod genes. In wheat cultivars from the Yellow and Huai Valleys, which
      represent 60%-70% of the total wheat production in China, the large-scale
      genotyping of wheat germplasms has not yet been performed in terms of
      vernalization and photoperiod response alleles, limiting the use of Chinese wheat
      germplasms to a certain extent. RESULTS: In this study, 173 winter wheat
      cultivars and 51 spring wheat cultivars from China were used to identify allelic
      variations of vernalization and photoperiod genes as well as copy number
      variations of Ppd-B1 and Vrn-A1. Two new co-dominant markers were developed in
      order to more precisely examine Vrn-A1b, Vrn-B1a, and Vrn-B1b. Two novel alleles
      at the Vrn-B3 locus were discovered and were designated Vrn-B3b and Vrn-B3c. Vrn
      B3b had an 890-bp insertion in the promoter region of the recessive vrn-B3
      allele, and Vrn-B3c allele had 2 deletions (a 20-bp deletion and a 4-bp deletion)
      in the promoter region of the dominant Vrn-B3a allele. Cultivar Hemai 26 lacked
      the Vrn-A1 gene. RT-PCR indicated that the 890-bp insertion in the Vrn-B3b allele
      significantly reduced the transcription of the Vrn-B3 gene. Cultivars Chadianhong
      with the Vrn-B3b allele and Hemai 26 with a Vrn-A1-null allele possessed
      relatively later heading and flowering times compared to those of Yanzhan 4110,
      which harbored recessive vrn-B3 and vrn-A1 alleles. Through identification of
      photoperiod genes, 2 new polymorphism combinations were found in 6 winter wheat
      cultivars and were designated Hapl-VII and Hapl-VIII, respectively. Distribution
      of the vernalization and photoperiod genes indicated that all recessive alleles
      at the 4 vernalization response loci, truncated "Chinese Spring" Ppd-B1 allele at
      Ppd-B1 locus and Hapl-I at the Ppd-D1 locus were predominant in Chinese winter
      wheat cultivars. CONCLUSION: This study illustrated the distribution of
      vernalization and photoperiod genes and identified 2 new Vrn-B3 alleles, 1 Vrn-A1
      null allele, and two new Ppd-D1 polymorphism combinations, using developed
      functional markers. Results of this study have the potential to provide useful
      information for screening relatively superior wheat cultivars for better
      adaptability and maturity.

PMID- 24314022
TI  - Sample size calculation based on exact test for assessing differential expression
      analysis in RNA-seq data.
AB  - BACKGROUND: Sample size calculation is an important issue in the experimental
      design of biomedical research. For RNA-seq experiments, the sample size
      calculation method based on the Poisson model has been proposed; however, when
      there are biological replicates, RNA-seq data could exhibit variation
      significantly greater than the mean (i.e. over-dispersion). The Poisson model
      cannot appropriately model the over-dispersion, and in such cases, the negative
      binomial model has been used as a natural extension of the Poisson model. Because
      the field currently lacks a sample size calculation method based on the negative
      binomial model for assessing differential expression analysis of RNA-seq data, we
      propose a method to calculate the sample size. RESULTS: We propose a sample size
      calculation method based on the exact test for assessing differential expression
      analysis of RNA-seq data. CONCLUSIONS: The proposed sample size calculation
      method is straightforward and not computationally intensive. Simulation studies
      to evaluate the performance of the proposed sample size method are presented; the
      results indicate our method works well, with achievement of desired power.

PMID- 24314023
TI  - Mir-655 up-regulation suppresses cell invasion by targeting pituitary tumor
      transforming gene-1 in esophageal squamous cell carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs) can act as either oncogenes or tumor suppressor
      genes under different conditions and thus can play a significant role in cancer
      development. We investigated miR-655 expression in a cohort of esophageal
      squamous cell carcinoma (ESCC) to assess the impact of this miRNA on ESCC cell
      invasion and metastasis. METHODS: A qRT-PCR assay was used to quantify miR-655
      expression levels in 34 paired ESCC samples and adjacent non-tumor tissues. Wound
      healing and transwell assays were used to evaluate the effects of miR-655
      expression on the invasiveness of ESCC cells. Luciferase reporter and western
      blot assays were used to determine whether the mRNA encoding pituitary tumor
      transforming gene-1 (PTTG1) is a major target of miR-655. RESULTS: The expression
      level of miR-655 in ESCC tissues was found to be lower than in adjacent non-tumor
      tissues (P < 0.05). This relatively low expression level was significantly
      associated with the occurrence of lymph node metastases (P < 0.05). Migration
      rates were significantly lower for two ESCC-derived cell lines (EC9706 and
      KYSE150) transfected with miR-429 mimics (P < 0.05). Subsequent western blot and
      luciferase reporter assays demonstrated that miR-655 could bind to putative
      binding sites within the PTTG1 mRNA 3'-untranslated region (3'-UTR) and thus
      reduce the expression. CONCLUSIONS: miR-655 is expressed at low levels in primary
      ESCC tissues, and up-regulation of miR-655 inhibits ESCC cell invasiveness by
      targeting PTTG1. Our findings suggest that PTTG1 may act as a major target of miR
      655. This study improves our understanding of the mechanisms underlying ESCC
      pathogenesis and may promote the development of novel targeted therapies.

PMID- 24314024
TI  - Mosquito transmission, growth phenotypes and the virulence of malaria parasites.
AB  - BACKGROUND: A series of elegant experiments was recently published which
      demonstrated that transmission of malaria parasites through mosquitoes elicited
      an attenuated growth phenotype, whereby infections grew more slowly and reached
      peak parasitaemia at least five-fold lower than parasites which had not been
      mosquito transmitted. To assess the implications of these results it is essential
      to understand whether the attenuated infection phenotype is a general phenomenon
      across parasites genotypes and conditions. METHODS: Using previously published
      data, the impact of mosquito transmission on parasite growth rates and virulence
      of six Plasmodium chabaudi lines was analysed. RESULTS: The effect of mosquito
      transmission varied among strains, but did not lead to pronounced or consistent
      reductions in parasite growth rate. CONCLUSIONS: Mosquito-induced attenuated
      growth phenotype is sensitive to experimental conditions.

PMID- 24314026
TI  - Learning to swim in a sea of genomic data.
AB  - A report on the 63rd American Society of Human Genetics (ASHG) meeting held in
      Boston, USA, 22-26 October 2013. 

PMID- 24314027
TI  - Promoting social responsibility amongst health care users: medical tourists'
      perspectives on an information sheet regarding ethical concerns in medical
      tourism.
AB  - BACKGROUND: Medical tourists, persons that travel across international borders
      with the intention to access non-emergency medical care, may not be adequately
      informed of safety and ethical concerns related to the practice of medical
      tourism. Researchers indicate that the sources of information frequently used by
      medical tourists during their decision-making process may be biased and/or lack
      comprehensive information regarding individual safety and treatment outcomes, as
      well as potential impacts of the medical tourism industry on third parties. This
      paper explores the feedback from former Canadian medical tourists regarding the
      use of an information sheet to address this knowledge gap and raise awareness of
      the safety and ethical concerns related to medical tourism. RESULTS: According to
      feedback provided in interviews with former Canadian medical tourists, the
      majority of participants responded positively to the information sheet and
      indicated that this document prompted them to engage in further consideration of
      these issues. Participants indicated some frustration after reading the
      information sheet regarding a lack of know-how in terms of learning more about
      the concerns discussed in the document and changing their decision-making. This
      frustration was due to participants' desperation for medical care, a topic which
      participants frequently discussed regarding ethical concerns related to health
      care provision. CONCLUSIONS: The overall perceptions of former medical tourists
      indicate that an information sheet may promote further consideration of ethical
      concerns of medical tourism. However, given that these interviews were performed
      with former medical tourists, it remains unknown whether such a document might
      impact upon the decision-making of prospective medical tourists. Furthermore,
      participants indicated a need for an additional tool such as a website for
      continued discussion about these concerns. As such, along with dissemination of
      the information sheet, future research implications should include the
      development of a website for ongoing discussion that could contribute to a raised
      awareness of these concerns and potentially increase social responsibility in the
      medical tourism industry.

PMID- 24314028
TI  - Face engagement during infancy predicts later face recognition ability in younger
      siblings of children with autism.
AB  - Face recognition difficulties are frequently documented in children with autism
      spectrum disorders (ASD). It has been hypothesized that these difficulties result
      from a reduced interest in faces early in life, leading to decreased cortical
      specialization and atypical development of the neural circuitry for face
      processing. However, a recent study by our lab demonstrated that infants at
      increased familial risk for ASD, irrespective of their diagnostic status at 3
      years, exhibit a clear orienting response to faces. The present study was
      conducted as a follow-up on the same cohort to investigate how measures of early
      engagement with faces relate to face-processing abilities later in life. We also
      investigated whether face recognition difficulties are specifically related to an
      ASD diagnosis, or whether they are present at a higher rate in all those at
      familial risk. At 3 years we found a reduced ability to recognize unfamiliar
      faces in the high-risk group that was not specific to those children who received
      an ASD diagnosis, consistent with face recognition difficulties being an
      endophenotype of the disorder. Furthermore, we found that longer looking at faces
      at 7 months was associated with poorer performance on the face recognition task
      at 3 years in the high-risk group. These findings suggest that longer looking at
      faces in infants at risk for ASD might reflect early face-processing difficulties
      and predicts difficulties with recognizing faces later in life.

PMID- 24314025
TI  - Molecular chaperones and protein folding as therapeutic targets in Parkinson's
      disease and other synucleinopathies.
AB  - Changes in protein metabolism are key to disease onset and progression in many
      neurodegenerative diseases. As a prime example, in Parkinson's disease, folding,
      post-translational modification and recycling of the synaptic protein alpha
      synuclein are clearly altered, leading to a progressive accumulation of
      pathogenic protein species and the formation of intracellular inclusion bodies.
      Altered protein folding is one of the first steps of an increasingly understood
      cascade in which alpha-synuclein forms complex oligomers and finally distinct
      protein aggregates, termed Lewy bodies and Lewy neurites. In neurons, an
      elaborated network of chaperone and co-chaperone proteins is instrumental in
      mediating protein folding and re-folding. In addition to their direct influence
      on client proteins, chaperones interact with protein degradation pathways such as
      the ubiquitin-proteasome-system or autophagy in order to ensure the effective
      removal of irreversibly misfolded and potentially pathogenic proteins. Because of
      the vital role of proper protein folding for protein homeostasis, a growing
      number of studies have evaluated the contribution of chaperone proteins to
      neurodegeneration. We herein review our current understanding of the involvement
      of chaperones, co-chaperones and chaperone-mediated autophagy in
      synucleinopathies with a focus on the Hsp90 and Hsp70 chaperone system. We
      discuss genetic and pathological studies in Parkinson's disease as well as
      experimental studies in models of synucleinopathies that explore molecular
      chaperones and protein degradation pathways as a novel therapeutic target. To
      this end, we examine the capacity of chaperones to prevent or modulate
      neurodegeneration and summarize the current progress in models of Parkinson's
      disease and related neurodegenerative disorders. 

PMID- 24314029
TI  - Characterization of a periplasmic nitrate reductase in complex with its
      biosynthetic chaperone.
AB  - Escherichia coli is a Gram-negative bacterium that can use nitrate during
      anaerobic respiration. The catalytic subunit of the periplasmic nitrate reductase
      NapA contains two types of redox cofactor and is exported across the cytoplasmic
      membrane by the twin-arginine protein transport pathway. NapD is a small
      cytoplasmic protein that is essential for the activity of the periplasmic nitrate
      reductase and binds tightly to the twin-arginine signal peptide of NapA. Here we
      show, using spin labelling and EPR, that the isolated twin-arginine signal
      peptide of NapA is structured in its unbound form and undergoes a small but
      significant conformational change upon interaction with NapD. In addition, a
      complex comprising the full-length NapA protein and NapD could be isolated by
      engineering an affinity tag onto NapD only. Analytical ultracentrifugation
      demonstrated that the two proteins in the NapDA complex were present in a 1 : 1
      molar ratio, and small angle X-ray scattering analysis of the complex indicated
      that NapA was at least partially folded when bound by its NapD partner. A NapDA
      complex could not be isolated in the absence of the NapA Tat signal peptide.
      Taken together, this work indicates that the NapD chaperone binds primarily at
      the NapA signal peptide in this system and points towards a role for NapD in the
      insertion of the molybdenum cofactor.

PMID- 24314030
TI  - Restoration of LRIG1 suppresses bladder cancer cell growth by directly targeting
      EGFR activity.
AB  - BACKGROUND: Recently, leucine-rich repeats and immunoglobulin-like domains 1
      (LRIG1), a negative regulator of EGFR, was discovered is a novel agent for
      suppressing bladder cancer. The aim of this study was to investigate the impact
      of LRIG1 on the biological features of aggressive bladder cancer cells and the
      possible mechanisms of enhanced apoptosis induced by upregulation of LRIG1.
      METHODS: In this study, we examined the mRNA and protein expression of LRIG1 and
      EGFR in bladder cancers and normal bladder. Meanwhile, we overexpressed LRIG1
      with adenovirus vector in T24/5637 bladder cancer cell lines, and we used real
      time-PCR, western blot, and co-immunoprecipitation analysis in order to examine
      the effects of LRIG1 gene on EGFR. Furthermore, we evaluate the impact of LRIG1
      gene on the function of human bladder cancer cells and EGFR signaling. RESULTS:
      The expression of LRIG1 was decreased, while the expression of EGFR was increased
      in the majority of bladder cancer, and the ratio of EGFR/LRIG1 was increased in
      tumors versus normal tissue. We found that upregulation of LRIG1 induced cell
      apoptosis and cell growth inhibition, and further reversed invasion in bladder
      cancer cell lines in vitro by inhibiting phosphorylation of downstream MAPK and
      AKT signaling pathway. CONCLUSION: Taken together, our findings provide us with
      an insight into LRIG1 function, and we conclude that LRIG1 evolved in bladder
      cancer as a rare feedback negative attenuator of EGFR, thus could offer a novel
      therapeutic target to treat patients with bladder cancer.

PMID- 24314031
TI  - Complications and outcomes of salvage robot-assisted radical prostatectomy: a
      single-institution experience.
AB  - OBJECTIVE: To determine the peri-operative outcomes of men undergoing salvage
      robot-assisted prostatectomy (RARP) and to examine the complications, functional
      consequences and need for additional treatments after salvage RARP. PATIENTS AND
      METHODS: At total of 51 consecutive patients underwent salvage RARP after
      previous failed local therapy. Biochemical recurrence (BCR) was defined as two
      postoperative PSA measurements >=0.2 ng/mL. Complications at any time
      postoperatively were recorded prospectively using a modified Clavien system. The
      Kaplan-Meier method was used for survival estimation, and regression models were
      used to identify the predictors of BCR or progression-free survival (PFS) and
      complications. RESULTS: The median age at salvage RARP was 68 years and a median
      of 68 months had elapsed from the time of primary treatment. The median follow-up
      was 36 months. The median operation duration was 179 min with a median estimated
      blood loss of 175 mL. In all, 50% of patients had pathological stage 3 disease
      and positive surgical margins were found in 31% of patients. The estimated 3-year
      BCR-free or PFS was 57%. The overall complication rate was 47%, with a 35% major
      complication rate (Grade III-V). Potency was maintained in 23% of preoperatively
      potent patients and 45% of all patients regained urinary control. No clinical
      variables were predictive of major complications, but all patients with
      postoperative bladder neck contracture were incontinent. A higher PSA level and
      extracapsular extension were significantly associated with BCR or progression (P
      < 0.01). CONCLUSIONS: Salvage RARP provides oncological control with potential
      avoidance of systemic non-curative therapy. Complication, incontinence and
      erectile dysfunction rates are significant but frequently correctable. This
      reinforces the need for proper patient counselling and selection.

PMID- 24314032
TI  - The impact of chronic disease self-management programs: healthcare savings
      through a community-based intervention.
AB  - BACKGROUND: Among the most studied evidence-based programs, the Chronic Disease
      Self-Management Program (CDSMP) has been shown to help participants improve their
      health behaviors, health outcomes, and reduce healthcare utilization. However,
      there is a lack of information on how CDSMP, when nationally disseminated,
      impacts healthcare utilization and averts healthcare costs. The purposes of this
      study were to: 1) document reductions in healthcare utilization among national
      CDSMP participants; 2) calculate potential cost savings associated with emergency
      room (ER) visits and hospitalizations; and 3) extrapolate the cost savings
      estimation to the American adults. METHODS: The national study of CDSMP surveyed
      1,170 community-dwelling CDSMP participants at baseline, 6 months, and 12 months
      from 22 organizations in 17 states. The procedure used to estimate potential cost
      savings included: 1) examining the pattern of healthcare utilization among CDSMP
      participants from self-reported healthcare utilization assessed at baseline, 6
      months, and 12 months; 2) calculating age-adjusted average costs for persons
      using the 2010 Medical Expenditure Panel Survey; 3) calculating costs saved from
      reductions in healthcare utilization; 4) estimating per participant program
      costs; 5) computing potential cost savings by deducting program costs from
      estimated healthcare savings; and 6) extrapolating savings to national
      populations using Census data combined with national health statistics. RESULTS:
      Findings from analyses showed significant reductions in ER visits (5%) at both
      the 6-month and 12-month assessments as well as hospitalizations (3%) at 6 months
      among national CDSMP participants. This equates to potential net savings of $364
      per participant and a national savings of $3.3 billion if 5% of adults with one
      or more chronic conditions were reached. CONCLUSIONS: Findings emphasize the
      value of public health tertiary prevention interventions and the need for
      policies to support widespread adoption of CDSMP.

PMID- 24314033
TI  - Fragment assignment in the cloud with eXpress-D.
AB  - BACKGROUND: Probabilistic assignment of ambiguously mapped fragments produced by
      high-throughput sequencing experiments has been demonstrated to greatly improve
      accuracy in the analysis of RNA-Seq and ChIP-Seq, and is an essential step in
      many other sequence census experiments. A maximum likelihood method using the
      expectation-maximization (EM) algorithm for optimization is commonly used to
      solve this problem. However, batch EM-based approaches do not scale well with the
      size of sequencing datasets, which have been increasing dramatically over the
      past few years. Thus, current approaches to fragment assignment rely on
      heuristics or approximations for tractability. RESULTS: We present an
      implementation of a distributed EM solution to the fragment assignment problem
      using Spark, a data analytics framework that can scale by leveraging compute
      clusters within datacenters-"the cloud". We demonstrate that our implementation
      easily scales to billions of sequenced fragments, while providing the exact
      maximum likelihood assignment of ambiguous fragments. The accuracy of the method
      is shown to be an improvement over the most widely used tools available and can
      be run in a constant amount of time when cluster resources are scaled linearly
      with the amount of input data. CONCLUSIONS: The cloud offers one solution for the
      difficulties faced in the analysis of massive high-thoughput sequencing data,
      which continue to grow rapidly. Researchers in bioinformatics must follow
      developments in distributed systems-such as new frameworks like Spark-for ways to
      port existing methods to the cloud and help them scale to the datasets of the
      future. Our software, eXpress-D, is freely available at:
      http://github.com/adarob/express-d.

PMID- 24314034
TI  - A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie
      tooth disease.
AB  - BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder of the
      peripheral nervous system. So far, mutations in hydroxyacyl-CoA dehydrogenase/3
      ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit
      (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation
      with cardiomyopathy, hepatic form with recurrent hypoketotic hypoglycemia, and
      later-onset axonal sensory neuropathy with episodic myoglobinuria. METHODS: To
      identify the causative and characterize clinical features of a Korean family with
      motor and sensory neuropathies, whole exome study (WES), histopathologic study of
      distal sural nerve, and lower limb MRIs were performed. RESULTS: WES revealed
      that a compound heterozygous mutation in HADHB is the causative of the present
      patients. The patients exhibited an early-onset axonal sensorimotor neuropathy
      without episodic myoglobinuria, and showed typical clinical and
      electrophysiological features of CMT including predominant distal muscle weakness
      and atrophy. Histopathologic findings of sural nerve were compatible with an
      axonal CMT neuropathy. Furthermore, they didn't exhibit any other symptoms of the
      previously reported HADHB patients. CONCLUSIONS: These data implicate that
      mutation in HADHB gene can also cause early-onset axonal CMT instead of typical
      manifestations in mitochondrial trifunctional protein (MTP) deficiency.
      Therefore, this study is the first report of a new subtype of autosomal recessive
      axonal CMT by a compound heterozygous mutation in HADHB, and will expand the
      clinical and genetic spectrum of HADHB.

PMID- 24314035
TI  - Doping dependence of low-energy quasiparticle excitations in superconducting
      Bi2212.
AB  - : The doping-dependent evolution of the d-wave superconducting state is studied
      from the perspective of the angle-resolved photoemission spectra of a high-Tc
      cuprate, Bi2Sr2CaCu2 O8+delta (Bi2212). The anisotropic evolution of the energy
      gap for Bogoliubov quasiparticles is parametrized by critical temperature and
      superfluid density. The renormalization of nodal quasiparticles is evaluated in
      terms of mass enhancement spectra. These quantities shed light on the strong
      coupling nature of electron pairing and the impact of forward elastic or
      inelastic scatterings. We suggest that the quasiparticle excitations in the
      superconducting cuprates are profoundly affected by doping-dependent screening. 

PMID- 24314036
TI  - Pythium species from rice roots differ in virulence, host colonization and
      nutritional profile.
AB  - BACKGROUND: Progressive yield decline in Philippine aerobic rice fields has been
      recently associated with three closely related Pythium spp., P. arrhenomanes, P.
      graminicola and P. inflatum. To understand their differential virulence towards
      rice seedlings, we conducted a comparative survey in which three isolates each of
      P. arrhenomanes, P. graminicola and P. inflatum were selected to investigate host
      colonization, host responses and carbon utilization profiles using
      histopathological analyses, phenoarrays, DNA quantifications and gene expression
      studies. RESULTS: The isolate of the most virulent species, P. arrhenomanes,
      quickly colonized the outer and inner root tissues of rice seedlings, including
      the xylem, by which it possibly blocked the water transport and induced severe
      stunting, wilting and seedling death. The lower virulence of the tested P.
      graminicola and P. inflatum isolates seemed to be reflected in slower
      colonization processes, limited invasion of the vascular stele and less systemic
      spread, in which cell wall fortification appeared to play a role. Progressive
      hyphal invasions triggered the production of reactive oxygen species (ROS) and
      phenolic compounds, which was the strongest for the P. arrhenomanes isolate and
      was delayed or much weaker upon inoculation with the P. inflatum isolate. The
      necrosis marker OsJamyb seemed faster and stronger induced by the most virulent
      isolates. Although the isolate of P. inflatum was nutritionally the most
      versatile, the most virulent Pythium isolate appeared physiologically more
      adapted to its host, evidenced by its broad amino acid utilization profile,
      including D-amino acids, L-threonine and hydroxyl-L-proline. The latter two
      compounds have been implicated in plant defense and their use by P. arrhenomanes
      could therefore represent a part of its virulence strategy. CONCLUSIONS: This
      study illustrates that the differential virulence of rice-pathogenic P.
      arrhenomanes, P. graminicola and P. inflatum isolates is related to their root
      colonization capacity, the intensity of induced root responses and their ability
      to utilize amino acids in their colonization niche. Accordingly, this paper
      presents important knowledge concerning rice root infections by oomycetes, which
      could be helpful to further disentangle virulence tactics of soil-borne
      pathogens.

PMID- 24314038
TI  - Role of 3D sonohysterography in the investigation of uterine synechiae/asherman's
      syndrome: pictorial assay.
AB  - Several imaging methods have been applied for evaluation of suspected uterine
      synechiae; however, sonohysterography is yet recognised as a valid and accurate
      modality. Performing three-dimensional (3D) imaging along with sonohysterography
      enables evaluation of the uterus in the coronal plane to detect and grade the
      adhesions that characterise this condition. Thus, 3D sonohysterography is a
      minimally invasive and cost-effective tool for investigating suspected synechiae
      and is particularly useful when the transvaginal sonography findings are normal. 

PMID- 24314039
TI  - Veterinary Nuclear Medicine. Letter from the editors.

PMID- 24314037
TI  - Changes in drug sensitivity and anti-malarial drug resistance mutations over time
      among Plasmodium falciparum parasites in Senegal.
AB  - BACKGROUND: Malaria treatment efforts are hindered by the rapid emergence and
      spread of drug resistant parasites. Simple assays to monitor parasite drug
      response in direct patient samples (ex vivo) can detect drug resistance before it
      becomes clinically apparent, and can inform changes in treatment policy to
      prevent the spread of resistance. METHODS: Parasite drug responses to
      amodiaquine, artemisinin, chloroquine and mefloquine were tested in approximately
      400 Plasmodium falciparum malaria infections in Thies, Senegal between 2008 and
      2011 using a DAPI-based ex vivo drug resistance assay. Drug resistance-associated
      mutations were also genotyped in pfcrt and pfmdr1. RESULTS: Parasite drug
      responses changed between 2008 and 2011, as parasites became less sensitive to
      amodiaquine, artemisinin and chloroquine over time. The prevalence of known
      resistance-associated mutations also changed over time. Decreased amodiaquine
      sensitivity was associated with sustained, highly prevalent mutations in pfcrt,
      and one mutation in pfmdr1 - Y184F - was associated with decreased parasite
      sensitivity to artemisinin. CONCLUSIONS: Directly measuring ex vivo parasite drug
      response and resistance mutation genotyping over time are useful tools for
      monitoring parasite drug responses in field samples. Furthermore, these data
      suggest that the use of amodiaquine and artemisinin derivatives in combination
      therapies is selecting for increased drug tolerance within this population.

PMID- 24314040
TI  - Guest editorial: Veterinary nuclear medicine.

PMID- 24314041
TI  - Musculoskeletal scintigraphy of the equine athlete.
AB  - Nuclear scintigraphic examination of equine athletes has a potentially important
      role in the diagnosis of lameness or poor performance, but increased
      radiopharmaceutical uptake (IRU) is not necessarily synonymous with pain causing
      lameness. Nuclear scintigraphy is highly sensitive to changes in bone turnover
      that may be induced by loading and knowledge of normal patterns of RU is crucial
      for accurate diagnosis. Blood pool images can be useful for identification of
      some soft tissue injuries, although acute bone injuries may also have intense IRU
      in blood pool images. Some muscle injuries may be associated with IRU in bone
      phase images. The use of scintigraphy together with other diagnostic imaging
      modalities has helped us to better understand the mechanisms of some
      musculoskeletal injuries. In immature racehorses, stress-related bone injury is a
      common finding and may be multifocal, whereas in mature sport horses, a very
      different spectrum of injuries may be identified. False-negative results are
      common with some injuries. 

PMID- 24314042
TI  - Liver scintigraphy in veterinary medicine.
AB  - The most common veterinary application of liver scintigraphy is for the diagnosis
      of portosystemic shunts (PSSs). There has been a continual evolution of nuclear
      medicine techniques for diagnosis of PSS, starting in the early 1980s. Currently,
      transplenic portal scintigraphy using pertechnetate or (99m)Tc-mebrofenin is the
      technique of choice. This technique provides both anatomical and functional
      information about the nature of the PSS, with high sensitivity and specificity.
      Hepatobiliary scintigraphy has also been used in veterinary medicine for the
      evaluation of liver function and biliary patency. Hepatobiliary scintigraphy
      provides information about biliary patency that complements finding in
      ultrasound, which may not be able to differentiate between biliary ductal
      dilation from previous obstruction vs current obstruction. Hepatocellular
      function can also be determined by deconvolutional analysis of hepatic uptake or
      by measuring the clearance of the radiopharmaceutical from the plasma. Plasma
      clearance of the radiopharmaceutical can be directly measured from serial plasma
      samples, as in the horse, or by measuring changes in cardiac blood pool activity
      by region of interest analysis of images. The objective of this paper is to
      present a summary of the reported applications of hepatobiliary scintigraphy in
      veterinary medicine. 

PMID- 24314043
TI  - Thyroid scintigraphy in veterinary medicine.
AB  - Thyroid scintigraphy is performed in cats and dogs and has been used to a limited
      degree in other species such as the horse. Thyroid scintigraphy is most commonly
      used to aid in the diagnosis and treatment management of feline hyperthyroidism
      but is also used in the evaluation of canine hypothyroidism and canine thyroid
      carcinoma. This article reviews the normal scintigraphic appearance of the
      thyroid in the cat, the dog, and the horse and the principles of interpretation
      of abnormal scan results in the cat and the dog. Radioiodine is the treatment of
      choice for feline hyperthyroidism, and the principles of its use in the cat are
      reviewed. 

PMID- 24314044
TI  - Renal scintigraphy in veterinary medicine.
AB  - Renal scintigraphy is performed commonly in dogs and cats and has been used in a
      variety of other species. In a 2012 survey of the members of the Society of
      Veterinary Nuclear Medicine, 95% of the respondents indicated they perform renal
      scintigraphy in their practice. Renal scintigraphy is primarily used to assess
      renal function and to evaluate postrenal obstruction. This article reviews how
      renal scintigraphy is used in veterinary medicine and describes the methods of
      analysis. Species variation is also discussed. 

PMID- 24314045
TI  - PET and SPECT imaging in veterinary medicine.
AB  - Veterinarians have gained increasing access to positron emission tomography (PET
      and PET/CT) imaging facilities, allowing them to use this powerful molecular
      imaging technique for clinical and research applications. SPECT is currently
      being used more in Europe than in the United States and has been shown to be
      useful in veterinary oncology and in the evaluation of orthopedic diseases. SPECT
      brain perfusion and receptor imaging is used to investigate behavioral disorders
      in animals that have interesting similarities to human psychiatric disorders.
      This article provides an overview of the potential applications of PET and SPECT.
      The use of commercially available and investigational PET radiopharmaceuticals in
      the management of veterinary disease has been discussed. To date, most of the
      work in this field has utilized the commercially available PET tracer, (18)F
      fluorodeoxyglucose for oncologic imaging. Normal biodistribution studies in
      several companion animal species (cats, dogs, and birds) have been published to
      assist in lesion detection and interpretation for veterinary radiologists and
      clinicians. Studies evaluating other (18)F-labeled tracers for research
      applications are underway at several institutions and companion animal models of
      human diseases are being increasingly recognized for their value in biomarker and
      therapy development. Although PET and SPECT technologies are in their infancy for
      clinical veterinary medicine, increasing access to and interest in these
      applications and other molecular imaging techniques has led to a greater
      knowledge and collective body of expertise for veterinarians worldwide.
      Initiation and fostering of physician-veterinarian collaborations are key
      components to the forward movement of this field. 

PMID- 24314046
TI  - Small-animal research imaging devices.
AB  - The scientific study of living animals may be dated to Aristotle's original
      dissections, but modern animal studies are perhaps a century in the making, and
      advanced animal imaging has emerged only during the past few decades. In vivo
      imaging now occupies a growing role in the scientific research paradigm. Imaging
      of small animals has been particularly useful to help understand human molecular
      biology and pathophysiology using rodents, especially using genetically
      engineered mice (GEM) with spontaneous diseases that closely mimic human
      diseases. Specific examples of GEM models of veterinary diseases exist, but in
      general, GEM for veterinary research has lagged behind human research
      applications. However, the development of spontaneous disease models from GEM may
      also hold potential for veterinary research. The imaging techniques most widely
      used in small-animal research are CT, PET, single-photon emission CT, MRI, and
      optical fluorescent and luminescent imaging. 

PMID- 24314047
TI  - Perspectives in molecular imaging through translational research, human medicine,
      and veterinary medicine.
AB  - The concept of molecular imaging has taken off over the past 15 years to the
      point of the renaming of the Society of Nuclear Medicine (Society of Nuclear
      Medicine and Molecular Imaging) and Journals (European Journal of Nuclear
      Medicine and Molecular Imaging) and offering of medical fellowships specific to
      this area of study. Molecular imaging has always been at the core of functional
      imaging related to nuclear medicine. Even before the phrase molecular imaging
      came into vogue, radionuclides and radiopharmaceuticals were developed that
      targeted select physiological processes, proteins, receptor analogs, antibody
      antigen interactions, metabolites and specific metabolic pathways. In addition,
      with the advent of genomic imaging, targeted genomic therapy, and theranostics, a
      number of novel radiopharmaceuticals for the detection and therapy of specific
      tumor types based on unique biological and cellular properties of the tumor
      itself have been realized. However, molecular imaging and therapeutics as well as
      the concept of theranostics are yet to be fully realized. The purpose of this
      review article is to present an overview of the translational approaches to
      targeted molecular imaging with application to some naturally occurring animal
      models of human disease. 

PMID- 24314048
TI  - Gene-gene interaction network analysis of ovarian cancer using TCGA data.
AB  - BACKGROUND: The Cancer Genome Atlas (TCGA) Data portal provides a platform for
      researchers to search, download, and analysis data generated by TCGA. The
      objective of this study was to explore the molecular mechanism of ovarian cancer
      pathogenesis. METHODS: Microarray data of ovarian cancer were downloaded from
      TCGA database, and Limma package in R language was used to identify the
      differentially expressed genes (DEGs) between ovarian cancer and normal samples,
      followed by the function and pathway annotations of the DEGs. Next, NetBox
      software was used to for the gene-gene interaction (GGI) network construction and
      the corresponding modules identification, and functions of genes in the modules
      were screened using DAVID. RESULTS: Our studies identified 332 DEGs, including
      146 up-regulated genes which mainly involved in the cell cycle related functions
      and cell cycle pathway, and 186 down-regulated genes which were enriched in
      extracellular region par function, and Ether lipid metabolism pathway. GGI
      network was constructed by 127 DEGs and their significantly interacted 209 genes
      (LINKERs). In the top 10 nodes ranked by degrees in the network, 5 were LINKERs.
      Totally, 7 functional modules in the network were selected, and they were
      enriched in different functions and pathways, such as mitosis process, DNA
      replication and DNA double-strand synthesis, lipid synthesis processes and
      metabolic pathways. AR, BRCA1, TFDP1, FOXM1, CDK2, and DBF4 were identified as
      the transcript factors of the 7 modules. CONCLUSION: our data provides a
      comprehensive bioinformatics analysis of genes, functions, and pathways which may
      be involved in the pathogenesis of ovarian cancer.

PMID- 24314049
TI  - Control strategies to re-establish glenohumeral stability after shoulder injury.
AB  - BACKGROUND: Muscles are important "sensors of the joint instability". The aim of
      this study was to identify the neuro-motor control strategies adopted by patients
      with anterior shoulder instability during overhead shoulder elevation in two
      planes. METHODS: The onset, time of peak activation, and peak magnitude of seven
      shoulder muscles (posterior deltoid, bilateral upper trapezius, biceps brachii,
      infraspinatus, supraspinatus and teres major) were identified using
      electromyography as 19 pre-operative patients with anterior shoulder instability
      (mean 27.95 years, SD = 7.796) and 25 age-matched asymptomatic control subjects
      (mean 23.07 years, SD = 2.952) elevated their arm above 90 degrees in the
      sagittal and coronal planes. RESULTS: Temporal characteristics of time of muscle
      onsets were significantly different between groups expect for teres major in the
      coronal plane (t = 1.1220, p = 0.2646) Patients recruited the rotator cuff
      muscles earlier and delayed the onset of ipsilateral upper trapezius compared
      with subjects (p<0.001) that control subjects. Furthermore, significant alliances
      existed between the onsets of infraspinatus and supraspinatus (sagittal: r =
      0.720; coronal: r = 0.756 at p<0.001) and ipsilateral upper trapezius and
      infraspinatus (sagittal: r = -0.760, coronal: r = -0.818 at p<0.001). The peak
      activation of all seven muscles occurred in the mid-range of elevation among
      patients with anterior shoulder instability whereas subjects spread peak
      activation of all 7 muscles throughout range. Peak magnitude of patients'
      infraspinatus muscle was six times higher (sagittal: t = -8.6428, coronal: t = 
      54.1578 at p<0.001) but magnitude of their supraspinatus was lower (sagittal: t =
      36.2507, coronal: t = 35.9350 at p<0.001) that subjects. CONCLUSIONS: Patients
      with anterior shoulder instability adopted a "stability before mobility" neuro
      motor control strategy to initiate elevation and a "stability at all cost"
      strategy to ensure concavity compression in the mid-to-150 degrees of elevation
      in both sagittal and coronal planes.

PMID- 24314050
TI  - Preoperative predictors of renal function decline after radical
      nephroureterectomy for upper tract urothelial carcinoma.
AB  - OBJECTIVES: To model renal function after radical nephroureterectomy (RNU) for
      upper tract urothelial carcinoma (UTUC). To identify predictors of renal function
      decline after surgery, thereby allowing the identification of patients likely to
      be ineligible for cisplatin-based chemotherapy in the adjuvant setting. PATIENTS
      AND METHODS: We retrospectively identified 374 patients treated with RNU for UTUC
      at three centres between 1995 and 2010. Estimated glomerular filtration rate
      (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration
      equation before RNU and at early (1-5 months after RNU) and late (>5 months) time
      points after RNU. Only patients deemed eligible for cisplatin-based chemotherapy
      before RNU (preoperative glomerular filtration rate [GFR] >=60 mL/min/1.73 m(2) )
      were included. Multivariable analysis identified the preoperative predictors of
      eGFR after RNU at early postoperative and late postoperative time points.
      RESULTS: A total of 163 patients had an eligible early post-RNU eGFR measurement
      and 172 had an eligible late eGFR measurement. The median eGFR declined by 32%
      and did not show a significant trend toward recovery over time (P = 0.4). On
      multivariable analysis preoperative eGFR and patient age were significantly
      associated with early and late postoperative eGFR, while Charlson comorbidity
      index score was significantly associated with late postoperative eGFR alone.
      CONCLUSIONS: In patients with normal preoperative eGFR (>=60 mL/min/1.73 m(2) ),
      renal function decreases by one-third after RNU and does not show evidence of
      recovery over time. Elderly patients and those with pre-RNU eGFR closer to 60
      mL/min/1.73 m(2) (lower eGFR in the present cohort) are more likely to be
      ineligible for adjuvant cisplatin-based chemotherapy regimens because of renal
      function loss after RNU.

PMID- 24314051
TI  - ERAD and protein import defects in a sec61 mutant lacking ER-lumenal loop 7.
AB  - BACKGROUND: The Sec61 channel mediates protein translocation across the
      endoplasmic reticulum (ER) membrane during secretory protein biogenesis, and
      likely also during export of misfolded proteins for ER-associated degradation
      (ERAD). The mechanisms of channel opening for the different modes of
      translocation are not understood so far, but the position of the large ER-lumenal
      loop 7 of Sec61p suggests a decisive role. RESULTS: We show here that the Y345H
      mutation in L7 which causes diabetes in the mouse displays no ER import defects
      in yeast, but a delay in misfolded protein export. A complete deletion of L7 in
      Sec61p resulted in viable, cold- and tunicamycin-hypersensitive yeast cells with
      strong defects in posttranslational protein import of soluble proteins into the
      ER, and in ERAD of soluble substrates. Membrane protein ERAD was only moderately
      slower in sec61?L7 than in wildtype cells. Although Sec61?L7 channels were
      unstable in detergent, co-translational protein integration into the ER membrane,
      proteasome binding to Sec61?L7 channels, and formation of hetero-heptameric Sec
      complexes were not affected. CONCLUSIONS: We conclude that L7 of Sec61p is
      required for initiation of posttranslational soluble protein import into and
      misfolded soluble protein export from the ER, suggesting a key role for L7 in
      transverse gating of the Sec61 channel.

PMID- 24314052
TI  - Sequencing of the IL6 gene in a case-control study of cerebral palsy in children.
AB  - BACKGROUND: Cerebral palsy (CP) is a group of nonprogressive disorders of
      movement and posture caused by abnormal development of, or damage to, motor
      control centers of the brain. A single nucleotide polymorphism (SNP), rs1800795,
      in the promoter region of the interleukin-6 (IL6) gene has been implicated in the
      pathogenesis of CP by mediating IL-6 protein levels in amniotic fluid and cord
      plasma and within brain lesions. This SNP has been associated with other
      neurological, vascular, and malignant processes as well, often as part of a
      haplotype block. METHODS: To refine the regional genetic association with CP, we
      sequenced (Sanger) the IL6 gene and part of the promoter region in 250 infants
      with CP and 305 controls. RESULTS: We identified a haplotype of 7 SNPs that
      includes rs1800795. In a recessive model of inheritance, the variant haplotype
      conferred greater risk (OR = 4.3, CI = [2.0-10.1], p = 0.00007) than did the lone
      variant at rs1800795 (OR = 2.5, CI = [1.4-4.6], p = 0.002). The risk haplotype
      contains one SNP (rs2069845, CI = [1.2-4.3], OR = 2.3, p = 0.009) that disrupts a
      methylation site. CONCLUSIONS: The risk haplotype identified in this study
      overlaps with previously identified haplotypes that include additional promoter
      SNPs. A risk haplotype at the IL6 gene likely confers risk to CP, and perhaps
      other diseases, via a multi-factorial mechanism.

PMID- 24314053
TI  - Reduced self-control leads to disregard of an unfamiliar behavioral option: an
      experimental approach to the study of neuroenhancement.
AB  - BACKGROUND: Neuroenhancement (NE), the use of psychoactive substances in order to
      enhance a healthy individual's cognitive functioning from a proficient to an even
      higher level, is prevalent in student populations. According to the strength
      model of self-control, people fail to self-regulate and fall back on their
      dominant behavioral response when finite self-control resources are depleted. An
      experiment was conducted to test the hypothesis that ego-depletion will prevent
      students who are unfamiliar with NE from trying it. FINDINGS: 130 undergraduates,
      who denied having tried NE before (43% female, mean age = 22.76 +/- 4.15 years
      old), were randomly assigned to either an ego-depletion or a control condition.
      The dependent variable was taking an "energy-stick" (a legal nutritional
      supplement, containing low doses of caffeine, taurine and vitamin B), offered as
      a potential means of enhancing performance on the bogus concentration task that
      followed. Logistic regression analysis showed that ego-depleted participants were
      three times less likely to take the substance, OR = 0.37, p = .01. CONCLUSION:
      This experiment found that trying NE for the first time was more likely if an
      individual's cognitive capacities were not depleted. This means that mental
      exhaustion is not predictive for NE in students for whom NE is not the dominant
      response. Trying NE for the first time is therefore more likely to occur as a
      thoughtful attempt at self-regulation than as an automatic behavioral response in
      stressful situations. We therefore recommend targeting interventions at this
      inter-individual difference. Students without previous reinforcing NE experience
      should be provided with information about the possible negative health outcomes
      of NE. Reconfiguring structural aspects in the academic environment (e.g.
      lessening workloads) might help to deter current users.

PMID- 24314054
TI  - Low-dose oral desmopressin for treatment of nocturia and nocturnal enuresis in
      patients after radical cystectomy and orthotopic urinary diversion.
AB  - OBJECTIVES: To assess the effect of oral desmopressin on nocturia and nocturnal
      enuresis in patients after orthotopic neobladder reconstruction. PATIENTS AND
      METHODS: Of 55 patients who underwent radical cystectomy and orthotopic
      neobladder reconstruction at our medical centre in the period 2004-2011, 34
      patients were deemed eligible for the present study. Inclusion criteria were
      estimated glomerular filtration rate >50 mL/min/1.73 m(2) , normal baseline
      sodium serum level, intact daytime urinary continence, and any degree of nocturia
      or nocturnal enuresis. Patients were treated daily with oral desmopressin 0.1 mg
      at bedtime for 30 days and completed the Nocturia, Nocturnal Enuresis and Sleep
      Interruption Questionnaire at trial enrollment and closure. Sodium serum levels
      were monitored throughout. RESULTS: Three patients withdrew from the trial
      because of headaches or anxiety. The mean (sd) number of nocturnal voids
      decreased from 2.5 (1.4)/night at baseline to 1.5 (1.3)/night at trial closure (P
      = 0.015). The number of patients with one or no episodes of nocturnal enuresis
      per week increased from six to 12 (19 to 39%; P = 0.065). Thirteen patients (42%)
      reported an increase of a minimum 1-2 h of sleep until the first nocturnal void;
      all of them asked to continue the drug. No significant adverse events or changes
      in sodium level were observed. CONCLUSIONS: Bedtime treatment with low-dose oral
      desmopressin appears to decrease episodes of nocturia and nocturnal enuresis
      effectively and safely in ~50% of the patients with neobladder, allowing longer
      undisrupted sleep time and improved quality of life. Further investigation is
      warranted to determine if higher doses would result in a more meaningful clinical
      response.

PMID- 24314055
TI  - Quantitative FDG PET/CT in the community: experience from interpretation of
      outside oncologic PET/CT exams in referred cancer patients.
AB  - PURPOSE: Tertiary care institutions often deal with patients who have had a
      baseline positron emission tomography (PET)/computed tomography (CT) scan
      performed elsewhere. Little data exist regarding the quality of these PET/CT
      scans and whether they are fully suitable for qualitative or quantitative
      interpretation. We evaluated outside PET/CT scans from cancer patients referred
      to our institution and compared them with PET/CT scans acquired locally. METHODS:
      This Health Insurance Portability and Accountability Act-compliant retrospective
      study was approved by our institutional review board. Informed consent
      requirements were waived. One hundred seventy recent whole-body outside PET/CT
      exams from many sites were digitally imported into our radiology imaging system
      and reviewed for key quality metrics including time from injection until imaging,
      availability of patient height and weight information, serum glucose level and
      [(18) F]fluoro-2-deoxy-D-glucose (FDG) dose. The standardised uptake value (SUV)
      and SUV based on lean body mass (SUL) in the liver were measured whenever
      possible. These were compared with 170 internal studies performed at our centre
      during the same period. RESULTS: Missing data were common in outside scans with
      height in 62%, weight 35%, uptake time 25%, FDG dose 28% and glucose levels in
      64% of cases. In quantitatively evaluable cases, mean liver SUL, SUV, FDG dose
      and uptake time were much more variable in outside than in internal studies.
      CONCLUSION: Approximately one-third of the outside PET/CT studies submitted
      digitally for analysis lacked key information required to secure any quantitative
      imaging data. Only about a third of these studies had all necessary information
      available for accurate SUL determination and had acceptable quality that was
      comparable with locally acquired scans. This suggests that many of PET studies
      performed in the community cannot be relied upon to provide quantitative image
      data that can be applied in a different centre. Greater standardisation of
      oncologic PET/CT studies among different centres must still be pursued.

PMID- 24314056
TI  - Room-temperature synthesis of zinc oxide nanoparticles in different media and
      their application in cyanide photodegradation.
AB  - Cyanide is an extreme hazard and extensively found in the wastes of refinery,
      coke plant, and metal plating industries. A simple, fast, cost-effective, room
      temperature wet chemical route, based on cyclohexylamine, for synthesizing zinc
      oxide nanoparticles in aqueous and enthanolic media was established and tested
      for the photodegradation of cyanide ions. Particles of polyhedra morphology were
      obtained for zinc oxide, prepared in ethanol (ZnOE), while spherical and some
      chunky particles were observed for zinc oxide, prepared in water (ZnOW). The
      morphology was crucial in enhancing the cyanide ion photocatalytic degradation
      efficiency of ZnOE by a factor of 1.5 in comparison to the efficiency of ZnOW at
      an equivalent concentration of 0.02 wt.% ZnO. Increasing the concentration wt.%
      of ZnOE from 0.01 to 0.09 led to an increase in the photocatalytic degradation
      efficiency from 85% to almost 100% after 180 min and a doubling of the first
      order rate constant (k). 

PMID- 24314057
TI  - Kinetic and kinematic differences between deadlifts and goodmornings.
AB  - BACKGROUND: In order to improve training performance, as well as avoid
      overloading during prevention and rehabilitation exercises in patients, the aim
      of this study was to understand the biomechanical differences in the knee, hip
      and the back between the exercises "Goodmornings" (GMs) and "Deadlifts" (DLs).
      METHODS: The kinetics and kinematics of 13 subjects, performing GMs and DLs with
      an additional 25% (GMs), 25% and 50% (DLs) body weight (BW) on the barbell were
      analysed. Using the kinetic and kinematic data captured using a 3D motion
      analysis and force plates, an inverse approach with a quasi-static solution was
      used to calculate the sagittal moments and angles in the knee, hip and the trunk.
      The maximum moments and joint angles were statistically tested using ANOVA with a
      Bonferroni adjustment. RESULTS: The observed maximal flexion angle of the knee
      was 5.3 +/- 6.7 degrees  for GMs and 107.8 +/- 22.4 degrees  and 103.4 +/- 22.6
      degrees  for DLs with 25% and 50% BW respectively. Of the hip, the maximal
      flexion angle was 25% smaller during GMs compared to DLs. No difference in
      kinematics of the trunk between the two exercises was observed. For DLs, the
      resulting sagittal moment in the knee was an external flexion moment, whereas
      during GMs an external extension moment was present. Importantly, no larger
      sagittal knee joint moments were observed when using a heavier weight on the
      barbell during DLs, but higher sagittal moments were found at the hip and L4/L5.
      Compared to GMs, DLs produced a lower sagittal moment at the hip using 25% BW
      while generating the same sagittal moment at L4/L5. CONCLUSIONS: The two
      exercises exhibited different motion patterns for the lower extremities but not
      for the trunk. To strengthen the hip while including a large range of motion, DLs
      using 50% BW should be chosen. Due to their ability to avoid knee flexion or a
      knee flexion moment, GMs should be preferentially chosen over DLs as ACL rupture
      prevention exercises. Here, in order to shift the hamstring to quadriceps ratio
      towards the hamstrings, GMs should be favoured ahead of DLs using 50% BW before
      DLs using 25% BW.

PMID- 24314059
TI  - A rapid colorimetric screening method for vanillic acid and vanillin-producing
      bacterial strains.
AB  - AIM: To isolate a bacterial strain capable of biotransforming ferulic acid, a
      major component of lignin, into vanillin and vanillic acid by a rapid
      colorimetric screening method. METHODS AND RESULTS: For the production of
      vanillin, a natural aroma compound, we attempted to isolate a potential strain
      using a simple screening method based on pH change resulting from the degradation
      of ferulic acid. The strain Pseudomonas sp. AZ10 UPM exhibited a significant
      result because of colour changes observed on the assay plate on day 1 with a high
      intensity of yellow colour. The biotransformation of ferulic acid into vanillic
      acid by the AZ10 strain provided the yield (Yp/s ) and productivity (Pr ) of 1.08
      mg mg(-1) and 53.1 mg L(-1) h(-1) , respectively. In fact, new investigations
      regarding lignin degradation revealed that the strain was not able to produce
      vanillin and vanillic acid directly from lignin; however, partially digested
      lignin by mixed enzymatic treatment allowed the strain to produce 30.7 mg l(-1)
      and 1.94 mg l(-1) of vanillic acid and biovanillin, respectively. CONCLUSIONS:
      (i) The rapid colorimetric screening method allowed the isolation of a
      biovanillin producer using ferulic acid as the sole carbon source. (ii) Enzymatic
      treatment partially digested lignin, which could then be utilized by the strain
      to produce biovanillin and vanillic acid. SIGNIFICANCE AND IMPACT OF THE STUDY:
      To the best of our knowledge, this is the first study reporting the use of a
      rapid colorimetric screening method for bacterial strains producing vanillin and
      vanillic acid from ferulic acid.

PMID- 24314058
TI  - Serum lipids and lipoproteins in malaria--a systematic review and meta-analysis.
AB  - BACKGROUND: Serum lipid profile changes have been observed during malaria
      infection. The underlying biological mechanisms remain unclear. The aim of this
      paper is to provide an overview on those serum lipid profile changes, and to
      discuss possible underlying biological mechanisms and the role of lipids in
      malaria pathogenesis. METHODS: A systematic review and meta-analysis to determine
      lipid profile changes during malaria was conducted, following PRISMA guidelines.
      Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register
      of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African
      Index Medicus were searched for studies published up to 11 July, 2013, that
      measured serum lipid parameters in malaria patients. Also, major trial registries
      were searched. Mean differences in lipid profile parameters were combined in
      fixed and random effects meta-analysis, with a separate analysis for different
      groups of controls (healthy, other febrile illnesses or very low parasitaemia).
      These parameters were also compared between severe malaria and uncomplicated
      malaria. Funnel plots were used to test for publication bias. RESULTS: Of 2,518
      studies reviewed, 42 met the criteria for inclusion in the qualitative analysis,
      and of these, 15 reported the necessary data for inclusion in the meta-analysis
      for cholesterol; nine for high-density lipoprotein (HDL), eight for low-density
      lipoprotein (LDL), and nine for triglycerides, respectively. Total cholesterol,
      HDL and LDL concentrations were lower in malaria and other febrile diseases
      compared to healthy controls. The decline was more pronounced and statistically
      significant during malaria compared to other febrile diseases. These results were
      consistent across included studies. Triglycerides were raised compared to healthy
      controls, but not statistically significant when compared to symptomatic
      controls. CONCLUSIONS: This meta-analysis suggests that the observed lipid
      profile changes are characteristic for malaria. Although a definite link with the
      pathogenesis of malaria cannot yet be demonstrated, plausible hypotheses of
      biological mechanisms involving host lipid alterations and the pathogenesis of
      malaria exist. An increased research effort to elucidate the precise pathways is
      warranted, since this could lead to better understanding of malaria
      pathophysiology and consequently to novel treatment approaches.

PMID- 24314060
TI  - MAOA-Environment Interactions: results May Vary.

PMID- 24314061
TI  - Adolescent brain vulnerability and psychopathology through the generations: role
      of diet and dopamine.

PMID- 24314062
TI  - Neuroimaging of externalizing behaviors and borderline traits.

PMID- 24314063
TI  - TcNPR3 from Theobroma cacao functions as a repressor of the pathogen defense
      response.
AB  - BACKGROUND: Arabidopsis thaliana (Arabidopsis) NON-EXPRESSOR OF PR1 (NPR1) is a
      transcription coactivator that plays a central role in regulating the
      transcriptional response to plant pathogens. Developing flowers of homozygous
      npr3 mutants are dramatically more resistant to infection by the pathogenic
      bacterium Pseudomonas syringae, suggesting a role of NPR3 as a repressor of NPR1
      mediated defense response with a novel role in flower development. RESULTS: We
      report here the characterization of a putative NPR3 gene from the tropical tree
      species Theobroma cacao (TcNPR3). Like in Arabidopsis, TcNPR3 was constitutively
      expressed across a wide range of tissue types and developmental stages but with
      some differences in relative levels compared to Arabidopsis. To test the function
      of TcNPR3, we performed transgenic complementation analysis by introducing a
      constitutively expressing putative TcNPR3 transgene into an Arabidopsis npr3
      mutant. TcNPR3 expressing Arabidopsis plants were partially restored to the WT
      pathogen phenotype (immature flowers susceptible to bacterial infection). To test
      TcNPR3 function directly in cacao tissues, a synthetic microRNA targeting TcNPR3
      mRNA was transiently expressed in cacao leaves using an Agrobacterium
      infiltration method. TcNPR3 knock down leaf tissues were dramatically more
      resistance to infection with Phytophthora capsici in a leaf bioassay, showing
      smaller lesion sizes and reduced pathogen replication. CONCLUSIONS: We conclude
      that TcNPR3 functions similar to the Arabidopsis NPR3 gene in the regulation of
      the cacao defense response. Since TcNPR3 did not show a perfect complementation
      of the Arabidopsis NPR3 mutation, the possibility remains that other functions of
      TcNPR3 remain to be found. This novel knowledge can contribute to the breeding of
      resistant cacao varieties against pathogens through molecular markers based
      approaches or biotechnological strategies.

PMID- 24314064
TI  - Regionalization of the axial skeleton in the 'ambush predator' guild--are there
      developmental rules underlying body shape evolution in ray-finned fishes?
AB  - BACKGROUND: A long, slender body plan characterized by an elongate antorbital
      region and posterior displacement of the unpaired fins has evolved multiple times
      within ray-finned fishes, and is associated with ambush predation. The axial
      skeleton of ray-finned fishes is divided into abdominal and caudal regions,
      considered to be evolutionary modules. In this study, we test whether the
      convergent evolution of the ambush predator body plan is associated with
      predictable, regional changes in the axial skeleton, specifically whether the
      abdominal region is preferentially lengthened relative to the caudal region
      through the addition of vertebrae. We test this hypothesis in seven clades
      showing convergent evolution of this body plan, examining abdominal and caudal
      vertebral counts in over 300 living and fossil species. In four of these clades,
      we also examined the relationship between the fineness ratio and vertebral
      regionalization using phylogenetic independent contrasts. RESULTS: We report that
      in five of the clades surveyed, Lepisosteidae, Esocidae, Belonidae, Sphyraenidae
      and Fistulariidae, vertebrae are added preferentially to the abdominal region. In
      Lepisosteidae, Esocidae, and Belonidae, increasing abdominal vertebral count was
      also significantly related to increasing fineness ratio, a measure of elongation.
      Two clades did not preferentially add abdominal vertebrae: Saurichthyidae and
      Aulostomidae. Both of these groups show the development of a novel caudal region
      anterior to the insertion of the anal fin, morphologically differentiated from
      more posterior caudal vertebrae. CONCLUSIONS: The preferential addition of
      abdominal vertebrae in fishes with an elongate body shape is consistent with the
      existence of a conservative positioning module formed by the boundary between the
      abdominal and caudal vertebral regions and the anterior insertion of the anal
      fin. Dissociation of this module is possible, although less probable than changes
      in the independently evolving abdominal region. Dissociation of the axial
      skeleton-median fin module leads to increased regionalization within the caudal
      vertebral column, something that has evolved several times in bony fishes, and
      may be homologous with the sacral region of tetrapods. These results suggest that
      modularity of the axial skeleton may result in somewhat predictable evolutionary
      outcomes in bony fishes.

PMID- 24314065
TI  - Spine metastases in prostate cancer: comparison of technetium-99m-MDP whole-body
      bone scintigraphy, [(18) F]choline positron emission tomography(PET)/computed
      tomography (CT) and [(18) F]NaF PET/CT.
AB  - OBJECTIVE: To compare the diagnostic accuracy of the following imaging techniques
      in the detection of spine metastases, using magnetic resonance imaging (MRI) as a
      reference: whole-body bone scintigraphy (WBS) with technetium-99m-MDP, [18F]
      sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT)
      and [(18) F]-fluoromethylcholine (FCH) PET/CT. PATIENTS AND METHODS: The study
      entry criteria were biopsy-proven prostate cancer, a positive WBS consistent with
      bone metastases, and no history of androgen deprivation. Within 30 days of
      informed consent, trial scans were performed in random order. Scans were
      interpreted blindly for the purpose of a lesion-based analysis. The primary
      target variable was bone lesion (malignant/benign) and the 'gold standard' was
      MRI. RESULTS: A total of 50 men were recruited between May 2009 and March 2012.
      Their mean age was 73 years, their median PSA level was 84 ng/mL, and the mean
      Gleason score of the tumours was 7.7. A total of 46 patients underwent all four
      scans, while four missed one PET/CT scan. A total of 526 bone lesions were found
      in the 50 men: 363 malignant and 163 non-malignant according to MRI. Sensitivity,
      specificity, positive and negative predictive values and accuracy were: WBS: 51,
      82, 86, 43 and 61%; NaF-PET/CT: 93, 54, 82, 78 and 81%; and FCH-PET/CT: 85, 91,
      95, 75 and 87%, respectively. CONCLUSIONS: We found that FCH-PET/CT and NaF
      PET/CT were superior to WBS with regard to detection of prostate cancer bone
      metastases within the spine. The present results call into question the use of
      WBS as the method of choice in patients with hormone-naive prostate cancer.

PMID- 24314066
TI  - A longitudinal study of quality of life of earthquake survivors in L'Aquila,
      Italy.
AB  - BACKGROUND: People's well-being after loss resulting from an earthquake is a
      concern in countries prone to natural disasters. Most studies on post-earthquake
      subjective quality of life (QOL) have focused on the effects of psychological
      impairment and post-traumatic stress disorder (PTSD) on the psychological
      dimension of QOL. However, there is a need for studies focusing on QOL in
      populations not affected by PTSD or psychological impairment. The aim of this
      study was to estimate QOL changes over an 18-month period in an adult population
      sample after the L'Aquila 2009 earthquake. METHODS: The study was designed as a
      longitudinal survey with four repeated measurements performed at six monthly
      intervals. The setting was the general population of an urban environment after a
      disruptive earthquake. Participants included 397 healthy adult subjects.
      Exclusion criteria were comorbidities such as physical, psychological,
      psychiatric or neurodegenerative diseases at the beginning of the study. The
      primary outcome measure was QOL, as assessed by the WHOQOL-BREF instrument. A
      generalised estimating equation model was run for each WHOQOL-BREF domain.
      RESULTS: Overall, QOL scores were observed to be significantly higher 18 months
      after the earthquake in all WHOQOL-BREF domains. The model detected an average
      increase in the physical QOL scores (from 66.6 +/- 5.2 to 69.3 +/- 4.7),
      indicating a better overall physical QOL for men. Psychological domain scores
      (from 64.9 +/- 5.1 to 71.5 +/- 6.5) were observed to be worse in men than in
      women. Levels at the WHOQOL domain for psychological health increased from the
      second assessment onwards in women, indicating higher resiliency. Men averaged
      higher scores than women in terms of social relationships and the environmental
      domain. Regarding the physical, psychological and social domains of QOL, scores
      in the elderly group (age > 60) were observed to be similar to each other
      regardless of the significant covariates used. CONCLUSIONS: WHOQOL-BREF scores of
      the psychological domain displayed trends conditioned by age and education: older
      subjects experienced less satisfaction with psychological health on average. Less
      educated subjects always demonstrated the worst QOL scores. Gender, age and
      education impacted the variability of QOL in the environmental dimension in the
      elderly.

PMID- 24314068
TI  - Alcohol use disorders and risk of Parkinson's disease: findings from a Swedish
      national cohort study 1972-2008.
AB  - BACKGROUND: Alcohol has been suggested to be either protective of, or not
      associated with Parkinson's disease (PD). However, experimental animal studies
      indicate that chronic heavy alcohol consumption may have dopamine neurotoxic
      effects relevant for PD. We studied the association between diagnosed alcohol use
      disorders and PD. METHODS: All individuals in Sweden admitted with a diagnosis of
      an alcohol use disorder or appendicitis (reference group) between January 1, 1972
      and December 31, 2008 were identified through the Swedish National Inpatient
      Register, and followed for up to 37 years for a diagnosis of PD. We estimated
      hazard ratios (HR) with 95% confidence intervals (CI) and adjusted for age and
      sex. RESULTS: We found 1,741 (0.3%) cases of PD in the cohort of 602,930
      individuals, 1,083 (0.4%) among those admitted with an alcohol use disorder and
      658 (0.2%) of the individuals admitted with appendicitis. The mean follow-up time
      was 13.6 and 17.1 years, respectively. The HR for PD associated with an alcohol
      use disorder was 1.38 (CI 1.25-1.53) adjusted for age and sex. When the risk was
      estimated in age groups for first hospital admission with PD the highest risk was
      observed in the lowest age group, <=44, HR 2.39 (0.96-5.93), adjusted for age at
      exposure and sex. CONCLUSIONS: A history of an alcohol use disorder conferred an
      increased risk of admission with a diagnosis of Parkinson's disease in both women
      and men. In particular, the risk seemed higher at lower ages of first admission
      with Parkinson's disease.

PMID- 24314067
TI  - Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and
      anti-diabetes medications on malondialdehyde-modified low-density lipoprotein
      levels in statin-treated diabetes patients with coronary artery disease.
AB  - BACKGROUND: A residual risk of cardiovascular disease tends to persist despite
      standard prevention therapy with statins. This may stem partly from increased
      oxidized low-density lipoprotein (LDL) levels. However, how oxidized LDL can be
      further reduced beyond statin therapy in high-risk diabetes patients remains
      unclear. We aimed to clarify the clinical factors associated with oxidized LDL
      levels in statin-treated high-risk diabetes patients. METHODS: This cross
      sectional observational study included 210 diabetes patients with coronary artery
      diseases (CAD) who were treated with statins. We determined serum malondialdehyde
      modified LDL (MDA-LDL), LDL cholesterol, high-density lipoprotein (HDL)
      cholesterol, triglyceride (TG), remnant lipoprotein cholesterol, hemoglobin (Hb)
      A1c, adiponectin, and C-reactive protein (CRP) levels and investigated the
      factors influencing the MDA-LDL level. RESULTS: In univariate analysis, the MDA
      LDL level was significantly correlated with LDL cholesterol (p < 0.0001), TG (p <
      0.0001), HDL cholesterol (p = 0.017), and adiponectin (p = 0.001) levels but not
      with age, body mass index, waist circumference, blood pressure, or HbA1c levels.
      Even after adjusting for the LDL cholesterol level, the correlations between the
      MDA-LDL level and the TG, HDL cholesterol, and adiponectin levels were still
      significant. Among these significant factors, multivariate analysis revealed that
      the MDA-LDL level was independently associated with the LDL cholesterol, TG, and
      HDL cholesterol but not with adiponectin levels. The MDA-LDL level was also
      significantly associated with the CRP level (p = 0.014) and the remnant
      lipoprotein cholesterol level (p < 0.0001) independently of the LDL cholesterol
      level. The number of metabolic syndrome (MS) components was significantly
      associated with the MDA-LDL/LDL cholesterol ratio (p < 0.0001). Furthermore, the
      use of metformin and alpha-glucosidase inhibitors was inversely associated with
      high MDA-LDL levels (p = 0.033 and 0.018, respectively). CONCLUSION: In statin
      treated diabetes patients with CAD, the MDA-LDL level was significantly
      correlated with TG and HDL cholesterol levels. Adiponectin level was also
      significantly associated with the MDA-LDL level, but not independent of the above
      mentioned factors. The management of dyslipidemic MS components, including the
      use of metformin or alpha-glucosidase inhibitors, may be important for reducing
      the oxidized LDL levels beyond statin therapy in high-risk diabetes patients.

PMID- 24314069
TI  - Gas in the rectum tends to reduce during radical external beam radiotherapy for
      localised prostate cancer.
AB  - PURPOSE: This study aims to clarify the time-course of gas accumulation in the
      rectum during treatment as guidance for the management of rectal volumes.
      MATERIALS AND METHODS: We reviewed 2042 sets (35.2 sets per patient) of
      anteroposterior and right-left mega voltage (MV) images obtained for daily set-up
      from 58 patients who underwent radical external beam radiotherapy for localised
      prostate cancer. The patients were instructed to take magnesium oxide tablets
      during radiotherapy. They were also encouraged to avoid foods that might cause
      intestinal gas during radiotherapy. Gas accumulation in the rectum was graded
      into three classes by the same radiation oncologist. If no gas was seen in the
      rectum, it was classified as grade 0. A small amount of gas was classified as
      grade 1, whereas a marked amount of gas that required removal was classified as
      grade 2. RESULTS: Of the 2042 sets of MV images, grades 1 and 2 gas accumulation
      were seen in 332 (16%) and 156 (8%), respectively. By the trend test, gas
      accumulation significantly decreased towards the end of treatment (P = 0.02 for
      grade 1 or 2 and P = 0.02 for grade 2). On multivariate analysis, we did not
      identify any significant independent predictors for either baseline gas
      accumulation or gas reduction. CONCLUSION: Gas accumulation tended to decrease
      until the end of treatment. This tendency should be reconfirmed by other
      institutions.

PMID- 24314070
TI  - Dementia special care units in residential care communities: United States, 2010.
AB  - In 2010, 17% of residential care communities had dementia special care units.
      Beds in dementia special care units accounted for 13% of all residential care
      beds. Residential care communities with dementia special care units were more
      likely than those without to have more beds, be chain-affiliated, and be
      purposely built as a residential care community, and less likely to be certified
      or registered to participate in Medicaid. Residential care communities with
      dementia special care units were more likely than those without to be located in
      the Northeast and in a metropolitan statistical area, and less likely to be in
      the West. Assisted living and similar residential care communities provide an
      alternative to nursing homes for individuals with dementia who can no longer live
      independently. In 2010, about 42% of individuals living in residential care
      communities had Alzheimer's disease or other dementia. Individuals with dementia
      can live in residential care communities that have dementia special care units,
      or in a more traditional setting where these residents are integrated with
      residents without dementia. Many states require residential care communities with
      dementia special care units to have certain physical features (e.g., locked door)
      and specially trained staff to care for residents with dementia. This report
      compares residential care communities with and without dementia special care
      units.

PMID- 24314071
TI  - Annealing temperature and environment effects on ZnO nanocrystals embedded in
      SiO2: a photoluminescence and TEM study.
AB  - We report on efficient ZnO nanocrystal (ZnO-NC) emission in the near-UV region.
      We show that luminescence from ZnO nanocrystals embedded in a SiO2 matrix can
      vary significantly as a function of the annealing temperature from 450 degrees C
      to 700 degrees C. We manage to correlate the emission of the ZnO nanocrystals
      embedded in SiO2 thin films with transmission electron microscopy images in order
      to optimize the fabrication process. Emission can be explained using two main
      contributions, near-band-edge emission (UV range) and defect-related emissions
      (visible). Both contributions over 500 degrees C are found to be size dependent
      in intensity due to a decrease of the absorption cross section. For the smallest
      size nanocrystals, UV emission can only be accounted for using a blueshifted UV
      contribution as compared to the ZnO band gap. In order to further optimize the
      emission properties, we have studied different annealing atmospheres under oxygen
      and under argon gas. We conclude that a softer annealing temperature at 450
      degrees C but with longer annealing time under oxygen is the most preferable
      scenario in order to improve near-UV emission of the ZnO nanocrystals embedded in
      an SiO2 matrix. 

PMID- 24314072
TI  - Outcomes of high-dose intensity-modulated radiotherapy alone with 1 cm planning
      target volume posterior margin for localized prostate cancer.
AB  - BACKGROUND: Clinically localized prostate cancer may be treated by different
      approaches of radiation therapy. The aim of this study was to report the results
      of disease control and toxicity in patients with clinically localized prostate
      cancer treated with high dose IMRT alone with 1 cm PTV posterior margin. METHODS:
      From September 2001 to April 2008, 140 patients with localized prostate cancer
      were treated with definitive IMRT (dose >= 74 Gy) without hormone therapy.
      Outcomes were measured from the conclusion of radiotherapy. Biochemical failure
      was defined as PSA nadir + 2.0 ng/dL. Toxicities were assessed using the NCI
      CTCAE-version 3.0. Median follow-up was 58 months. RESULTS: Biochemical failure
      occurred in 13.6% of patients. Actuarial 5-year biochemical control rates were
      91.7%, 82.5% and 85.9% for low-, intermediate-, and high-risk patients,
      respectively. Stage T2 patients presented a risk of biochemical failure almost
      three times higher than stage T1 (RR = 2.91; 95% CI: 1.04; 8.17). Distant
      metastases occurred in 3 (2%) patients. Five-year metastasis-free and overall
      survivals were 96% and 97.5%, respectively. Late grade 3 genitourinary and
      gastrointestinal toxicity rates were, respectively, 1.6% and 3%. CONCLUSION: High
      dose IMRT alone with 1 cm posterior PTV margin was effective and safe for
      patients with localized prostate cancer.

PMID- 24314073
TI  - Extracellular micronutrient levels and pro-/antioxidant status in trauma patients
      with wound healing disorders: results of a cross-sectional study.
AB  - BACKGROUND: Disorders in wound healing (DWH) are common in trauma patients, the
      reasons being not completely understood. Inadequate nutritional status may favor
      DWH, partly by means of oxidative stress. Reliable data, however, are lacking.
      This study should investigate the status of extracellular micronutrients in
      patients with DWH within routine setting. METHODS: Within a cross-sectional
      study, the plasma/serum status of several micronutrients (retinol, ascorbic acid,
      25-hydroxycholecalciferol, alpha-tocopherol, beta-carotene, selenium, and zinc)
      were determined in 44 trauma patients with DWH in addition to selected proteins
      (albumin, prealbumin, and C-reactive protein; CRP) and markers of pro
      /antioxidant balance (antioxidant capacity, peroxides, and malondialdehyde).
      Values were compared to reference values to calculate the prevalence for
      biochemical deficiency. Correlations between CRP, albumin and prealbumin, and
      selected micronutrients were analyzed by Pearson's test. Statistical significance
      was set at P < 0.05. RESULTS: Mean concentrations of ascorbic acid (23.1 +/- 15.9
      MUmol/L), 25-hydroxycholecalciferol (46.2+/-30.6 nmol/L), beta-carotene (0.6 +/-
      0.4 MUmol/L), selenium (0.79+/-0.19 MUmol/L), and prealbumin (24.8 +/- 8.2 mg/dL)
      were relatively low. Most patients showed levels of ascorbic acid (<28 MUmol/L;
      64%), 25-hydroxycholecalciferol (<50 MUmol/L; 59%), selenium (<= 94 MUmol/L; 71%)
      and beta-carotene (<0.9 MUmol/L; 86%) below the reference range. Albumin and
      prealbumin were in the lower normal range and CRP was mostly above the reference
      range. Plasma antioxidant capacity was decreased, whereas peroxides and
      malondialdehyde were increased compared to normal values. Inverse correlations
      were found between CRP and albumin (P < 0.05) and between CRP and prealbumin (P <
      0.01). Retinol (P < 0.001), ascorbic acid (P < 0.01), zinc (P < 0.001), and
      selenium (P < 0.001) were negatively correlated with CRP. CONCLUSIONS: Trauma
      patients with DWH frequently suffer from protein malnutrition and reduced plasma
      concentrations of several micronutrients probably due to inflammation, increased
      requirement, and oxidative burden. Thus, adequate nutritional measures are
      strongly recommended to trauma patients.

PMID- 24314074
TI  - A complex partnership: KCNQ1 and KCNE1.

PMID- 24314075
TI  - Long-lived intracellular single-molecule fluorescence using electroporated
      molecules.
AB  - Studies of biomolecules in vivo are crucial to understand their function in a
      natural, biological context. One powerful approach involves fusing molecules of
      interest to fluorescent proteins to study their expression, localization, and
      action; however, the scope of such studies would be increased considerably by
      using organic fluorophores, which are smaller and more photostable than their
      fluorescent protein counterparts. Here, we describe a straightforward, versatile,
      and high-throughput method to internalize DNA fragments and proteins labeled with
      organic fluorophores into live Escherichia coli by employing electroporation. We
      studied the copy numbers, diffusion profiles, and structure of internalized
      molecules at the single-molecule level in vivo, and were able to extend single
      molecule observation times by two orders of magnitude compared to green
      fluorescent protein, allowing continuous monitoring of molecular processes
      occurring from seconds to minutes. We also exploited the desirable properties of
      organic fluorophores to perform single-molecule Forster resonance energy transfer
      measurements in the cytoplasm of live bacteria, both for DNA and proteins.
      Finally, we demonstrate internalization of labeled proteins and DNA into yeast
      Saccharomyces cerevisiae, a model eukaryotic system. Our method should broaden
      the range of biological questions addressable in microbes by single-molecule
      fluorescence.

PMID- 24314076
TI  - Pleomorphic ensembles: formation of large clusters composed of weakly interacting
      multivalent molecules.
AB  - Molecular interactions of importance to cell biology are subject to sol-gel
      transitions: large clusters of weakly interacting multivalent molecules (gel
      phase) are produced at a critical concentration of monomers. Examples include
      cell-cell and cell-matrix adhesions, nucleoprotein bodies, and cell signaling
      platforms. We use the term pleomorphic ensembles (PEs) to describe these
      clusters, because they have dynamic compositions and sizes and have rapid
      turnover of their molecular constituents; this plasticity can be highly
      responsive to cellular signals. The classical polymer physical chemistry theory
      developed by Flory and Stockmayer provides a brilliant framework for treating
      multivalent interactions for simple idealized systems. But the complexity and
      variability of PEs challenges existing modeling approaches. Here we describe and
      validate a computational algorithm that extends the Flory-Stockmayer formalism to
      overcome the limitations of analytic theories. We divide the problem by
      deterministically calculating the fraction of bound sites for each type of
      binding site, followed by the stochastic assignment of the bonds to a finite
      number of molecules. The method allows for high valency within many different
      kinds of interacting molecules and site types, permits simulation of steady-state
      distributions, as well as assembly kinetics, and can treat cooperative binding
      within one of the interacting molecules. We then apply our method to the analysis
      of interactions in the nephrin-Nck-N-Wasp signaling system, demonstrating how
      multivalent layered scaffolds produce PEs at low monomer concentrations despite
      weak binding interactions. We show how the experimental data for this system are
      most consistent with synergistic cooperative interactions between Nck and N-Wasp.

PMID- 24314077
TI  - Building KCNQ1/KCNE1 channel models and probing their interactions by molecular
      dynamics simulations.
AB  - The slow delayed rectifier (I(KS)) channel is composed of KCNQ1 (pore-forming)
      and KCNE1 (auxiliary) subunits, and functions as a repolarization reserve in the
      human heart. Design of I(KS)-targeting anti-arrhythmic drugs requires detailed
      three-dimensional structures of the KCNQ1/KCNE1 complex, a task made possible by
      Kv channel crystal structures (templates for KCNQ1 homology-modeling) and KCNE1
      NMR structures. Our goal was to build KCNQ1/KCNE1 models and extract mechanistic
      information about their interactions by molecular-dynamics simulations in an
      explicit lipid/solvent environment. We validated our models by confirming two
      sets of model-generated predictions that were independent from the spatial
      restraints used in model-building. Detailed analysis of the molecular-dynamics
      trajectories revealed previously unrecognized KCNQ1/KCNE1 interactions, whose
      relevance in I(KS) channel function was confirmed by voltage-clamp experiments.
      Our models and analyses suggest three mechanisms by which KCNE1 slows KCNQ1
      activation: by promoting S6 bending at the Pro hinge that closes the activation
      gate; by promoting a downward movement of gating charge on S4; and by
      establishing a network of electrostatic interactions with KCNQ1 on the
      extracellular surface that stabilizes the channel in a pre-open activated state.
      Our data also suggest how KCNE1 may affect the KCNQ1 pore conductance.

PMID- 24314078
TI  - Factors determining the recruitment of inositol trisphosphate receptor channels
      during calcium puffs.
AB  - Puffs are localized, transient elevations in cytosolic Ca(2+) that serve both as
      the building blocks of global cellular Ca(2+) signals and as local signals in
      their own right. They arise from clustered inositol 1,4,5-trisphosphate
      receptor/channels (IP3Rs), whose openings are coordinated by Ca(2+)-induced
      Ca(2+) release (CICR). We utilized total internal reflection fluorescence imaging
      of Ca(2+) signals in neuroblastoma cells with single-channel resolution to
      elucidate the mechanisms determining the triggering, amplitudes, kinetics, and
      spatial spread of puffs. We find that any given channel in a cluster has a mean
      probability of ~66% of opening following opening of an initial "trigger" channel,
      and the probability of puff triggering thus increases steeply with increasing
      number of channels in a cluster (cluster size). Mean puff amplitudes scale with
      cluster size, but individual amplitudes vary widely, even at sites of similar
      cluster size, displaying similar proportions of events involving any given number
      of the channels in the cluster. Stochastic variation in numbers of Ca(2+)
      inhibited IP3Rs likely contributes to the variability of amplitudes of repeated
      puffs at a site but the amplitudes of successive puffs were uncorrelated, even
      though we observed statistical correlations between interpuff intervals and puff
      amplitudes. Initial puffs evoked following photorelease of IP3-which would not be
      subject to earlier Ca(2+)-inhibition-also showed wide variability, indicating
      that mechanisms such as stochastic variation in IP3 binding and channel
      recruitment by CICR further determine puff amplitudes. The mean termination time
      of puffs lengthened with increasing puff amplitude size, consistent with
      independent closings of channels after a given mean open time, but we found no
      correlation of termination time with cluster size independent of puff amplitude.
      The spatial extent of puffs increased with their amplitude, and puffs of similar
      size were of similar width, independent of cluster size.

PMID- 24314079
TI  - Short-chain phosphoinositide partitioning into plasma membrane models.
AB  - Phosphoinositides are vital for many cellular signaling processes, and therefore
      a number of approaches to manipulating phosphoinositide levels in cells or
      excised patches of cell membranes have been developed. Among the most common is
      the use of "short-chain" phosphoinositides, usually dioctanoyl phosphoinositol
      phosphates. We use isothermal titration calorimetry to determine partitioning of
      the most abundant phosphoinositol phosphates, PI(4)P and PI(4,5)P2 into models of
      the intracellular and extracellular facing leaflets of neuronal plasma membranes.
      We show that phosphoinositide mole fractions in the lipid membrane reach
      physiological levels at equilibrium with reasonable solution concentrations.
      Finally we explore the consequences of our results for cellular
      electrophysiology. In particular, we find that TRPV1 is more selective for
      PI(4,5)P2 than PI(4)P and activated by extremely low membrane mole fractions of
      PIPs. We conclude by discussing how the logic of our work extends to other
      experiments with short-chain phosphoinositides. For delayed rectifier K(+)
      channels, consideration of the membrane mole fraction of PI(4,5)P2 lipids with
      different acyl chain lengths suggests a different mechanism for PI(4,5)P2
      regulation than previously proposed. Inward rectifier K(+) channels apparent lack
      of selectivity for certain short-chain PIPs may require reinterpretation in view
      of the PIPs different membrane partitioning.

PMID- 24314080
TI  - Wild-type and mutant hemagglutinin fusion peptides alter bilayer structure as
      well as kinetics and activation thermodynamics of stalk and pore formation
      differently: mechanistic implications.
AB  - Viral fusion peptides are short N-terminal regions of type-1 viral fusion
      proteins that are critical for virus entry. Although the importance of viral
      fusion peptides in virus-cell membrane fusion is established, little is known
      about how they function. We report the effects of wild-type (WT) hemagglutinin
      (HA) fusion peptide and its G1S, G1V, and W14A mutants on the kinetics of
      poly(ethylene glycol)(PEG)-mediated fusion of small unilamellar vesicles composed
      of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine, sphingomyelin,
      and cholesterol (molar ratio of 35:30:15:20). Time courses of lipid mixing,
      content mixing, and content leakage were obtained using fluorescence assays at
      multiple temperatures and analyzed globally using either a two-step or three-step
      sequential ensemble model of the fusion process to obtain the rate constant and
      activation thermodynamics of each step. We also monitored the influence of
      peptides on bilayer interfacial order, acyl chain order, bilayer free volume, and
      water penetration. All these data were considered in terms of a recently
      published mechanistic model for the thermodynamic transition states for each step
      of the fusion process. We propose that WT peptide catalyzes Step 1 by occupying
      bilayer regions vacated by acyl chains that protrude into interbilayer space to
      form the Step 1 transition state. It also uniquely contributes a positive
      intrinsic curvature to hemi-fused leaflets to eliminate Step 2 and catalyzes Step
      3 by destabilizing the highly stressed edges of the hemi-fused microstructures
      that dominate the ensemble of the intermediate state directly preceding fusion
      pore formation. Similar arguments explain the catalytic and inhibitory properties
      of the mutant peptides and support the hypothesis that the membrane-contacting
      fusion peptide of HA fusion protein is key to its catalytic activity.

PMID- 24314081
TI  - Conformational dynamics of calcium-triggered activation of fusion by
      synaptotagmin.
AB  - Synaptotagmin triggers rapid exocytosis of neurotransmitters from synaptic
      vesicles in response to Calcium (Ca(2+)) ions. Here, we use a novel Nanodisc
      based system, designed to be a soluble mimetic of the clamped synaptic vesicle
      bilayer junction, combined with fluorescence resonance energy transfer (FRET)
      spectroscopy to monitor the structural relationships among SNAREs (soluble N
      ethylmaleimide-sensitive factor attachment protein receptor), Synaptotagmin C2
      domains, and the lipid bilayer in real time during the Ca(2+)-activation process.
      We report that Synaptotagmin remains rigidly fixed on the partially assembled
      SNARE complex with no detectable internal rearrangement of its C2 domains, even
      as it rapidly inserts into the bilayer. We hypothesize that this straightforward,
      one-step physical mechanism could explain how this Ca(2+)- sensor rapidly
      activates neurotransmitter release from the clamped state.

PMID- 24314082
TI  - Agonist leukadherin-1 increases CD11b/CD18-dependent adhesion via membrane
      tethers.
AB  - Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration
      and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that
      enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used
      single-molecule force spectroscopy to investigate the biophysical mechanism by
      which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two
      distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell
      adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane
      tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1
      via the formation of long membrane tethers, whereas Mn(2+) additionally increased
      ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1(-/-)
      neutrophils also showed longer detachment distances and time from ICAM-1-coated
      atomic force microscopy tips, but significantly lower detachment force, as
      compared to the Mn(2+)-activated cells, confirming that LA1 primarily increased
      membrane-tether bonds to enhance CD11b/CD18:ICAM-1 binding, whereas Mn(2+)
      induced additional CSK-anchored bond formation. The results suggest that the two
      types of agonists differentially activate integrins and couple them to the
      cellular machinery, providing what we feel are new insights into signal
      mechanotransduction by such agents.

PMID- 24314083
TI  - Brownian dynamics of subunit addition-loss kinetics and thermodynamics in linear
      polymer self-assembly.
AB  - The structure and free energy of multistranded linear polymer ends evolves as
      individual subunits are added and lost. Thus, the energetic state of the polymer
      end is not constant, as assembly theory has assumed. Here we utilize a Brownian
      dynamics approach to simulate the addition and loss of individual subunits at the
      polymer tip. Using the microtubule as a primary example, we examined how the
      structure of the polymer tip dictates the rate at which units are added to and
      lost from individual protofilaments. We find that freely diffusing subunits
      arrive less frequently to lagging protofilaments but bind more efficiently, such
      that there is no kinetic difference between leading and lagging protofilaments
      within a tapered tip. However, local structure at the nanoscale has up to an
      order-of-magnitude effect on the rate of addition. Thus, the kinetic on-rate
      constant, integrated across the microtubule tip (kon,MT), is an ensemble average
      of the varying individual protofilament on-rate constants (kon,PF). Our findings
      have implications for both catastrophe and rescue of the dynamic microtubule end,
      and provide a subnanoscale framework for understanding the mechanism of action of
      microtubule-associated proteins and microtubule-directed drugs. Although we
      utilize the specific example of the microtubule here, the findings are applicable
      to multistranded polymers generally.

PMID- 24314084
TI  - Thermodynamic analyses of nucleotide binding to an isolated monomeric beta
      subunit and the alpha3beta3gamma subcomplex of F1-ATPase.
AB  - Rotation of the gamma subunit of the F1-ATPase plays an essential role in energy
      transduction by F1-ATPase. Hydrolysis of an ATP molecule induces a 120 degrees 
      step rotation that consists of an 80 degrees  substep and 40 degrees  substep.
      ATP binding together with ADP release causes the first 80 degrees  step rotation.
      Thus, nucleotide binding is very important for rotation and energy transduction
      by F1-ATPase. In this study, we introduced a betaY341W mutation as an optical
      probe for nucleotide binding to catalytic sites, and a betaE190Q mutation that
      suppresses the hydrolysis of nucleoside triphosphate (NTP). Using a mutant
      monomeric betaY341W subunit and a mutant alpha3beta3gamma subcomplex containing
      the betaY341W mutation with or without an additional betaE190Q mutation, we
      examined the binding of various NTPs (i.e., ATP, GTP, and ITP) and nucleoside
      diphosphates (NDPs, i.e., ADP, GDP, and IDP). The affinity (1/Kd) of the
      nucleotides for the isolated beta subunit and third catalytic site in the
      subcomplex was in the order ATP/ADP > GTP/GDP > ITP/IDP. We performed van't Hoff
      analyses to obtain the thermodynamic parameters of nucleotide binding. For the
      isolated beta subunit, NDPs and NTPs with the same base moiety exhibited similar
      DeltaH(0) and DeltaG(0) values at 25 degrees C. The binding of nucleotides with
      different bases to the isolated beta subunit resulted in different entropy
      changes. Interestingly, NDP binding to the alpha3beta(Y341W)3gamma subcomplex had
      similar Kd and DeltaG(0) values as binding to the isolated beta(Y341W) subunit,
      but the contributions of the enthalpy term and the entropy term were very
      different. We discuss these results in terms of the change in the tightness of
      the subunit packing, which reduces the excluded volume between subunits and
      increases water entropy.

PMID- 24314085
TI  - Excited state dynamics can be used to probe donor-acceptor distances for H
      tunneling reactions catalyzed by flavoproteins.
AB  - In enzyme systems where fast motions are thought to contribute to H-transfer
      efficiency, the distance between hydrogen donor and acceptor is a very important
      factor. Sub-angstrom changes in donor-acceptor distance can have a large effect
      on the rate of reaction, so a sensitive probe of these changes is a vital tool in
      our understanding of enzyme function. In this study we use ultrafast transient
      absorption spectroscopy to investigate the photoinduced electron transfer rates,
      which are also very sensitive to small changes in distance, between coenzyme
      analog, NAD(P)H4, and the isoalloxazine center in the model flavoenzymes
      morphinone reductase (wild-type and selected variants) and pentaerythritol
      tetranitrate reductase (wild-type). It is shown that upon addition of coenzyme to
      the protein the rate of photoinduced electron transfer is increased. By comparing
      the magnitude of this increase with existing values for NAD(P)H4-FMN distances,
      based on charge-transfer complex absorbance and experimental kinetic isotope
      effect reaction data, we show that this method can be used as a sensitive probe
      of donor-acceptor distance in a range of enzyme systems.

PMID- 24314086
TI  - How DNA polymerase X preferentially accommodates incoming dATP opposite 8
      oxoguanine on the template.
AB  - The modified base 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxoG) is a common DNA
      adduct produced by the oxidation of DNA by reactive oxygen species. Kinetic data
      reveal that DNA polymerase X (pol X) from the African swine fever virus
      incorporates adenine (dATP) opposite to oxoG with higher efficiency than the non
      damaged G:C basepair. To help interpret the kinetic data, we perform molecular
      dynamics simulations of pol X/DNA complexes, in which the template base opposite
      to the incoming dNTP (dCTP, dATP, dGTP) is oxoG. Our results suggest that pol X
      accommodates the oxoGsyn:A mispair by sampling closed active conformations that
      mirror those observed in traditional Watson-Crick complexes. Moreover, for both
      the oxoGsyn:A and oxoG:C ternary complexes, conformational sampling of the
      polymerase follows previously described large subdomain movements, local residue
      motions, and active site reorganization. Interestingly, the oxoGsyn:A system
      exhibits superior active site geometry in comparison to the oxoG:C system.
      Simulations for the other mismatch basepair complexes reveal large protein
      subdomain movement for all systems, except for oxoG:G, which samples
      conformations close to the open state. In addition, active site geometry and
      basepairing of the template base with the incoming nucleotide, reveal distortions
      and misalignments that range from moderate (i.e., oxoG:Asyn) to extreme (i.e.,
      oxoGanti/syn:G). These results agree with the available kinetic data for pol X
      and provide structural insights regarding the mechanism by which this polymerase
      can accommodate incoming nucleotides opposite oxoG. Our simulations also support
      the notion that alpha-helix E is involved both in DNA binding and active site
      stabilization. Our proposed mechanism by which pol X can preferentially
      accommodate dATP opposite template oxoG further underscores the role that enzyme
      dynamics and conformational sampling operate in polymerase fidelity and function.

PMID- 24314087
TI  - The snakelike chain character of unstructured RNA.
AB  - In the absence of base-pairing and tertiary structure, ribonucleic acid (RNA)
      assumes a random-walk conformation, modulated by the electrostatic self-repulsion
      of the charged, flexible backbone. This behavior is often modeled as a Kratky
      Porod "wormlike chain" (WLC) with a Barrat-Joanny scale-dependent persistence
      length. In this study we report measurements of the end-to-end extension of
      poly(U) RNA under 0.1 to 10 pN applied force and observe two distinct elastic
      response regimes: a low-force, power-law regime characteristic of a chain of
      swollen blobs on long length scales and a high-force, salt-valence-dependent
      regime consistent with ion-stabilized crumpling on short length scales. This
      short-scale structure is additionally supported by force- and salt-dependent
      quantification of the RNA ion atmosphere composition, which shows that ions are
      liberated under stretching; the number of ions liberated increases with
      increasing bulk salt concentration. Both this result and the observation of two
      elastic-response regimes directly contradict the WLC model, which predicts a
      single elastic regime across all forces and, when accounting for scale-dependent
      persistence length, the opposite trend in ion release with salt concentration. We
      conclude that RNA is better described as a "snakelike chain," characterized by
      smooth bending on long length scales and ion-stabilized crumpling on short length
      scales. In monovalent salt, these two regimes are separated by a characteristic
      length that scales with the Debye screening length, highlighting the determining
      importance of electrostatics in RNA conformation.

PMID- 24314088
TI  - Strong ionic hydrogen bonding causes a spectral isotope effect in photoactive
      yellow protein.
AB  - Standard hydrogen bonds are of great importance for protein structure and
      function. Ionic hydrogen bonds often are significantly stronger than standard
      hydrogen bonds and exhibit unique properties, but their role in proteins is not
      well understood. We report that hydrogen/deuterium exchange causes a redshift in
      the visible absorbance spectrum of photoactive yellow protein (PYP). We expand
      the range of interpretable isotope effects by assigning this spectral isotope
      effect (SIE) to a functionally important hydrogen bond at the active site of PYP.
      The inverted sign and extent of this SIE is explained by the ionic nature and
      strength of this hydrogen bond. These results show the relevance of ionic
      hydrogen bonding for protein active sites, and reveal that the inverted SIE is a
      novel, to our knowledge, tool to probe ionic hydrogen bonds. Our results support
      a classification of hydrogen bonds that distinguishes the properties of ionic
      hydrogen bonds from those of both standard and low barrier hydrogen bonds, and
      show how this classification helps resolve a recent debate regarding active site
      hydrogen bonding in PYP.

PMID- 24314090
TI  - The role of semidisorder in temperature adaptation of bacterial FlgM proteins.
AB  - Probabilities of disorder for FlgM proteins of 39 species whose optimal growth
      temperature ranges from 273 K (0 degrees C) to 368 K (95 degrees C) were
      predicted by a newly developed method called Sequence-based Prediction with
      Integrated NEural networks for Disorder (SPINE-D). We showed that the temperature
      dependent behavior of FlgM proteins could be separated into two subgroups
      according to their sequence lengths. Only shorter sequences evolved to adapt to
      high temperatures (>318 K or 45 degrees C). Their ability to adapt to high
      temperatures was achieved through a transition from a fully disordered state with
      little secondary structure to a semidisordered state with high predicted helical
      probability at the N-terminal region. The predicted results are consistent with
      available experimental data. An analysis of all orthologous protein families in
      39 species suggests that such a transition from a fully disordered state to
      semidisordered and/or ordered states is one of the strategies employed by nature
      for adaptation to high temperatures.

PMID- 24314091
TI  - Immunomodulating activity of exopolysaccharide-producing Leuconostoc
      mesenteroides strain NTM048 from green peas.
AB  - AIMS: The present work was aimed to find novel probiotics to enhance the mucosal
      barrier function of humans. The effectiveness was evaluated in vitro and in vivo.
      METHODS AND RESULTS: Stimulation of IgA production in mucosal surfaces is one of
      the most beneficial traits of lactic acid bacteria (LAB) for enhancing the
      barrier. Therefore, 173 LAB strains were evaluated for the ability to induce IgA
      production using murine Peyer's patch cells. Strain NTM048 isolated from green
      peas showed the highest activity and was identified as Leuconostoc mesenteroides
      subsp. mesenteroides. This strain was found to tolerate gastrointestinal
      digestion and produce large amounts of exopolysaccharides, which possess IgA
      inducing activity. Dietary supplementation with NTM048 induced a significant
      increase in the faecal IgA content and plasma IgA levels of BALB/cA mice. A gene
      expression analysis of Peyer's patch cells revealed that the transforming growth
      factor-beta and activation-induced cytidine deaminase genes were upregulated by
      NTM048 intake. CONCLUSIONS: Strain NTM048 stimulates Peyer's patch cells to
      induce intestinal and systemic immune response, revealing the potential of NTM048
      as a probiotic for enhancing the mucosal barrier function. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This report demonstrates a food-applicable Leuconostoc
      mesenteroides strain secreting exopolysaccharide that shows high IgA-inducing
      ability.

PMID- 24314089
TI  - Characterization of structure, dynamics, and detergent interactions of the anti
      HIV chemokine variant 5P12-RANTES.
AB  - RANTES (CCL5) is a chemokine that recruits immune cells to inflammatory sites by
      interacting with the G-protein coupled receptor CCR5, which is also the primary
      coreceptor used together with CD4 by HIV to enter and infect target cells.
      Ligands of CCR5, including chemokines and chemokine analogs, are capable of
      blocking HIV entry, and studies of their structures and interactions with CCR5
      will be key to understanding and optimizing HIV inhibition. The RANTES derivative
      5P12-RANTES is a highly potent HIV entry inhibitor that is being developed as a
      topical HIV prevention agent (microbicide). We have characterized the structure
      and dynamics of 5P12-RANTES by solution NMR. With the exception of the nine
      flexible N-terminal residues, 5P12-RANTES has the same structure as wild-type
      RANTES but unlike the wild-type, does not dimerize via its N-terminus. To prepare
      the ground for interaction studies with detergent-solubilized CCR5, we have also
      investigated the interaction of RANTES and 5P12-RANTES with various commonly used
      detergents. Both RANTES variants are stable in Cymal-5, DHPC, Anzergent-3-12,
      dodecyltrimethylammonium chloride, and a DDM/CHAPS/CHS mixture. Fos-Cholines,
      dodecyldimethylglycine, and sodium dodecyl-sulfate denature both RANTES variants
      at low pH, whereas at neutral pH the stability is considerably higher. The onset
      of Fos-Choline-12-induced denaturation and the denatured state were characterized
      by circular dichroism and NMR. The detergent interaction starts below the
      critical micelle concentration at a well-defined mixed hydrophobic/positive
      surface region of the chemokine, which overlaps with the dimer interface. An
      increase of Fos-Choline-12 concentration above the critical micelle concentration
      causes a transition to a denatured state with a high alpha-helical content.

PMID- 24314092
TI  - Epigenetic rather than genetic factors may explain phenotypic divergence between
      coastal populations of diploid and tetraploid Limonium spp. (Plumbaginaceae) in
      Portugal.
AB  - BACKGROUND: The genus Limonium Miller comprises annual and perennial halophytes
      that can produce sexual and/or asexual seeds (apomixis). Genetic and epigenetic
      (DNA methylation) variation patterns were investigated in populations of three
      phenotypically similar putative sexual diploid species (L. nydeggeri, L.
      ovalifolium, L. lanceolatum), one sexual tetraploid species (L. vulgare) and two
      apomict tetraploid species thought to be related (L. dodartii, L. multiflorum).
      The extent of morphological differentiation between these species was assessed
      using ten diagnostic morphometric characters. RESULTS: A discriminant analysis
      using the morphometric variables reliably assigns individuals into their
      respective species groups. We found that only modest genetic and epigenetic
      differentiation was revealed between species by Methylation Sensitive
      Amplification Polymorphism (MSAP). However, whilst there was little separation
      possible between ploidy levels on the basis of genetic profiles, there was clear
      and pronounced interploidy discrimination on the basis of epigenetic profiles.
      Here we investigate the relative contribution of genetic and epigenetic factors
      in explaining the complex phenotypic variability seen in problematic taxonomic
      groups such as Limonium that operate both apomixis and sexual modes of
      reproduction. CONCLUSIONS: Our results suggest that epigenetic variation might be
      one of the drivers of the phenotypic divergence between diploid and tetraploid
      taxa and discuss that intergenome silencing offers a plausible mechanistic
      explanation for the observed phenotypic divergence between these microspecies.
      These results also suggest that epigenetic profiling offer an additional tool to
      infer ploidy level in stored specimens and that stable epigenetic change may play
      an important role in apomict evolution and species recognition.

PMID- 24314093
TI  - Everolimus and sunitinib for advanced pancreatic neuroendocrine tumors: a
      matching-adjusted indirect comparison.
AB  - BACKGROUND: Everolimus and sunitinib have been approved for the treatment
      advanced pancreatic neuroendocrine tumors, but have not been compared to each
      other in a randomized trial and have not demonstrated prolonged overall survival
      compared to placebo. This study aimed to indirectly compare overall and
      progression-free among everolimus, sunitinib and placebo across separate
      randomized trials. METHODS: A matching adjusted indirect comparison was conducted
      in which individual patient data from the pivotal trial of everolimus (n = 410)
      were adjusted to match the inclusion criteria and average baseline
      characteristics reported for the pivotal trial of sunitinib (n = 171). Prior to
      matching, trial populations differed in baseline performance status and prior
      treatments. After matching, these and all other available baseline
      characteristics were balanced between trials. RESULTS: Compared to the placebo
      arm in the sunitinib trial, everolimus was associated with significantly
      prolonged overall survival (HR = 0.61, 95% CI = 0.38-0.98, p = 0.042).Compared to
      sunitinib, everolimus was associated with similar progression-free (hazard ratio
      for death (HR) = 0.84, 95% CI = 0.46-1.53, p = 0.578) and overall survival (HR =
      0.81, 95% CI = 0.49-1.31, p = 0.383). CONCLUSION: After adjusting for observed
      cross-trial differences, everolimus treatment was associated with longer overall
      survival than the placebo arm in the sunitinib trial for advanced pancreatic
      neuroendocrine tumors.

PMID- 24314094
TI  - The girdles of the oldest fossil turtle, Proterochersis robusta, and the age of
      the turtle crown.
AB  - BACKGROUND: Proterochersis robusta from the Late Triassic (Middle Norian) of
      Germany is the oldest known fossil turtle (i.e. amniote with a fully formed
      turtle shell), but little is known about its anatomy. A newly prepared, historic
      specimen provides novel insights into the morphology of the girdles and vertebral
      column of this taxon and the opportunity to reassess its phylogenetic position.
      RESULTS: The anatomy of the pectoral girdle of P. robusta is similar to that of
      other primitive turtles, including the Late Triassic (Carnian) Proganochelys
      quenstedti, in having a vertically oriented scapula, a large coracoid foramen, a
      short acromion process, and bony ridges that connect the acromion process with
      the dorsal process, glenoid, and coracoid, and by being able to rotate along a
      vertical axis. The pelvic elements are expanded distally and suturally attached
      to the shell, but in contrast to modern pleurodiran turtles the pelvis is
      associated with the sacral ribs. CONCLUSIONS: The primary homology of the
      character "sutured pelvis" is unproblematic between P. robusta and extant
      pleurodires. However, integration of all new observations into the most complete
      phylogenetic analysis that support the pleurodiran nature of P. robusta reveals
      that this taxon is more parsimoniously placed along the phylogenetic stem of
      crown Testudines. All current phylogenetic hypotheses therefore support the basal
      placement of this taxon, imply that the sutured pelvis of this taxon developed
      independently from that of pleurodires, and conclude that the age of the turtle
      crown is Middle Jurassic.

PMID- 24314095
TI  - Obesity is associated with higher risk of prostate cancer detection in a biopsy
      population in Korea.
AB  - OBJECTIVE: To evaluate the impact of obesity on prostate cancer detection, as
      measured by the body mass index (BMI) in a Korean biopsy population. PATIENTS AND
      METHODS: We retrospectively reviewed the records of 1213 men who underwent
      transrectal ultrasonography-guided prostate biopsy at our institution. Biopsy
      outcomes were analysed with respect to various variables, including patient age,
      prostate-specific antigen (PSA), prostate volume, digital rectal examination
      (DRE) findings and obesity, defined as BMI >=25 kg/m(2) , an Asian BMI category.
      RESULTS: Among 1213 men, 408 (33.6%) were obese and 344 (28.4%) had a positive
      biopsy. Obese men were younger (65.5 vs 67.1 years, P = 0.003), had a larger
      prostate (49.2 vs 42.9 mL, P < 0.001) and were less likely to have any
      abnormality on DRE (8.1 vs 15.9% P < 0.001) than non-obese men. In the
      multivariate analysis, obesity was significantly associated with a higher risk of
      prostate cancer detection in men undergoing biopsy (odds ratio [OR] = 1.446, P =
      0.024). In addition, obesity was significantly associated with a higher rate of
      biopsy-detected high grade (Gleason score >=4 + 3) disease, and this association
      remained after multivariate adjustment (OR = 1.498, P = 0.039). CONCLUSIONS:
      Obese men were younger, had a larger prostate, and had less tendency to have an
      abnormality on DRE than non-obese men. Obesity was associated with a higher risk
      of prostate cancer detection as an independent factor, including high grade
      prostate cancer in a Korean biopsy population.

PMID- 24314096
TI  - Clinical and genetic features of Huntington disease in Sri Lanka.
AB  - BACKGROUND: Huntington disease was one of the first neurological hereditary
      diseases for which genetic testing was made possible as early as 1993. The study
      describes the clinical and genetic characteristics of patients with Huntington
      disease in Sri Lanka. METHODS: Data of 35 consecutive patients tested from 2007
      to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo
      was analyzed retrospectively. Clinical data and genetic diagnostic results were
      reviewed. Statistical analysis was performed using descriptive statistics.
      RESULTS: Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had
      reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset
      and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and
      64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2
      patients with Juvenile onset (<20 years) and 3 with late onset (>60 years)
      Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 
      91%). Three patients had psychiatric and behavioral disorders. The age difference
      between onset and genetic diagnosis showed significant delay in females compared
      to males (p < 0.05). Twenty two (62.8%) had a positive family history, with 13/22
      (59.1%) showing a paternal inheritance of the disease. In both groups, those with
      a family history had a significantly lower age of presentation (p < 0.05). The
      mean CAG repeat length in patients with FP alleles was 44.6 +/- 5 and RP alleles
      was 37.2 +/- 1.1. Age of onset and CAG repeat length of the HTT gene showed
      significant inverse correlation (p < 0.0005, R2 = 0.727). CONCLUSIONS: The
      clinical and genetic features seen in patients with Huntington disease in the Sri
      Lankan study population were similar to that previously reported in literature.

PMID- 24314097
TI  - A cross-sectional survey of experts' opinions about the relative effectiveness of
      tobacco control strategies for the general population versus disadvantaged
      groups: what do we choose in the absence of evidence?
AB  - BACKGROUND: There is a clear disparity in smoking rates according to social
      disadvantage. In the absence of sufficiently robust data regarding effective
      strategies for reducing smoking prevalence in disadvantaged populations,
      understanding the views of tobacco control experts can assist with funding
      decisions and research agendas. METHODS: A web-based cross-sectional survey was
      conducted with 192 respondents (response rate 65%) sampled from the Australian
      and New Zealand Tobacco Control Contacts list and a literature search.
      Respondents were asked to indicate whether a number of tobacco control strategies
      were perceived to be effective for each of: the general population; Aboriginal
      and Torres Strait Islander people; those with a low income; and people with a
      mental illness. RESULTS: A high proportion of respondents indicated that mass
      media and increased tobacco taxation (84% and 89% respectively) were effective
      for the general population. Significantly lower proportions reported these two
      strategies were effective for sub-populations, particularly Aboriginal and Torres
      Strait Islanders (58% and 63% respectively, p's < .0001). Subsidised medication
      was the only strategy associated with a greater proportion of respondents
      perceiving it to be effective in disadvantaged sub-populations compared to the
      general population. Tailored quit programs and culturally relevant programs were
      nominated as additional effective strategies for disadvantaged populations.
      CONCLUSIONS: Views about subsidised medications in particular, suggest the need
      for robust cost-effectiveness data relevant to disadvantaged groups to avoid
      wastage of scarce tobacco control resources. Strategies perceived to be effective
      for disadvantaged populations such as tailored or culturally relevant programs
      require rigorous evaluation so that potential adoption of these approaches is
      evidence-based.

PMID- 24314098
TI  - Evaluating the role of inbreeding depression in heterozygosity-fitness
      correlations: how useful are tests for identity disequilibrium?
AB  - Heterozygosity-fitness correlations (HFCs) have been observed for several
      decades, but their causes are often elusive. Tests for identity disequilibrium
      (ID, correlated heterozygosity between loci) are commonly used to determine if
      inbreeding depression is a possible cause of HFCs. We used computer simulations
      to determine how often ID is detected when HFCs are caused by inbreeding
      depression. We also used ID in conjunction with HFCs to estimate the proportion
      of variation (r(2)) in fitness explained by the individual inbreeding coefficient
      (F). ID was not detected in a large proportion of populations with statistically
      significant HFCs (sample size = 120 individuals) unless the variance of F was
      high (sigma(2)(F) >= 0.005) or many loci were used (100 microsatellites or 1000
      SNPs). For example, with 25 microsatellites, ID was not detected in 49% of
      populations when HFCs were caused by six lethal equivalents and sigma(2)(F) was
      typical of vertebrate populations (sigma(2)(F) ~ 0.002). Estimates of r(2)
      between survival and F based on ID and HFCs were imprecise unless ID was strong
      and highly statistically significant (P ~ 0.01). These results suggest that
      failing to detect ID in HFC studies should not be taken as evidence that
      inbreeding depression is absent. The number of markers necessary to
      simultaneously detect HFC and ID depends strongly on sigma(2)(F). Thus the mating
      system and demography of populations, which influence sigma(2) (F), should be
      considered when designing HFC studies. ID should be used in conjunction with HFCs
      to estimate the correlation between fitness and F, because HFCs alone reveal
      little about the strength of inbreeding depression.

PMID- 24314099
TI  - Shape-controllable synthesis of hydrophilic NaLuF4:Yb,Er nanocrystals by a
      surfactant-assistant two-phase system.
AB  - Water-soluble upconversion nanoparticles (UCNPs) were prepared by a one-pot
      procedure in a two-phase reacting system. Four kinds of surfactants were tested
      in the synthesis process as capping agent to tune size and morphology of
      nanocrystals. Nanoparticles (approximately 70 nm) and rods (400 nm and 2.5 MUm)
      were synthesized, respectively. Then, Fourier transform infrared spectroscopy
      analysis confirmed the successful linking between UCNP surface and surfactant.
      Ionic liquids (ILs) and surfactants participated in synthesis process together,
      competing with each other to cap on UCNPs. ILs still led the competition of
      capping, while surfactants worked as cooperative assistants to develop functional
      surface. Further characterizations such as high-resolution transmission electron
      microscopy and X-ray diffraction indicated the changes in crystallization and
      phase transformation under the influence of surfactants. In addition, the growth
      mechanism of nanocrystals and upconversion fluorescence luminance was also
      investigated in detail. At last, the cytotoxicity of UCNPs was evaluated, which
      highly suggest that these surface-functionalized UCNPs are promising candidates
      for biomedical engineering. 

PMID- 24314101
TI  - The role of segmental nodes in the pathological staging of non-small cell lung
      cancer.
AB  - BACKGROUND: Segmental nodes are not examined routinely in current clinical
      practice for lung cancer, the role of segmental nodes in pathological staging of
      non-small cell lung cancer after radical resection was investigated. METHODS: A
      total of 113 consecutive non-small cell lung cancer patients who underwent
      radical resection between June 2009 and December 2011 were retrospectively
      reviewed. All the operations were performed by the same group of surgeons. N2
      nodes, hilar nodes, interlobar nodes and some lobar nodes were collected during
      surgery. The removed lung lobes were dissected routinely along lobar and
      segmental bronchi to collect lobar nodes and segmental nodes. The collected lymph
      nodes were separately labeled for histological examination. RESULTS: The
      detection rates of hilar nodes, interlobar nodes, lobar nodes and segmental nodes
      were 61.1%, 85.0%, 75.2% and 80.5%, respectively. The metastasis rates of hilar
      nodes, interlobar nodes, lobar nodes and segmental nodes were 5.3%, 10.5%, 16.8%
      and 14.2%, respectively. There were 68 cases of N0 disease, 16 cases of N1
      disease and 29 cases of N2 disease. If an analysis of segmental lymph nodes had
      been omitted, six patients (37.5% of N1 disease) would have been down-staged to
      N0, and two cases of multiple-zone N1 disease would have been misdiagnosed as
      single-zone N1 disease, one patient would have been misdiagnosed as N2 disease
      with skip metastases. CONCLUSION: Segmental nodes play an important role in the
      accurate staging of non-small cell lung cancer, and routinely dissecting the
      segmental bronchi to collect the lymph nodes is feasible and may be necessary.

PMID- 24314102
TI  - Psychotropic medication use among adolescents: United States, 2005-2010.
AB  - Approximately 6.0% of U.S. adolescents aged 12-19 reported psychotropic drug use
      in the past month. The use of antidepressants (3.2%) and attention deficit
      hyperactive disorder (ADHD) drugs (3.2%) was highest, followed by antipsychotics
      (1.0%); anxiolytics, sedatives, and hypnotics (0.5%); and antimanics (0.2%).
      Males (4.2%) were more likely than females (2.2%) to use ADHD drugs. Females
      (4.5%) were more likely than males (2.0%) to use antidepressants. Psychotropic
      drug use was higher among non-Hispanic white (8.2%) adolescents than non-Hispanic
      black (3.1%) and Mexican-American (2.9%) adolescents. About one-half of U.S.
      adolescents using psychotropic drugs in the past month had seen a mental health
      professional in the past year (53.3%). Prior studies have shown an increase in
      psychotropic medication use among adolescents. However, most studies were based
      on clinical samples or high-risk populations. This report provides the estimate
      of any psychotropic medication use in the past month among U.S.
      noninstitutionalized adolescents aged 12-19 during 2005-2010, using National
      Health and Nutrition Examination Survey (NHANES) data. Psychotropic medication is
      a type of drug used to treat clinical psychiatric symptoms or mental disorders.
      Specific psychotropic drug types addressed are antidepressants; medications for
      attention deficit hyperactive disorder (ADHD); anxiolytics, sedatives, and
      hypnotics (ASH); antimanics; and antipsychotics. Adolescents using psychotropic
      drugs are further examined by sex, race and Hispanic origin, and mental health
      professional consultation.

PMID- 24314100
TI  - Pidotimod: the past and the present.
AB  - At the end of 1990s, acute respiratory tract infections (ARTIs) were called the
      'forgotten pandemic', with a clear dichotomy between developing and
      industrialised countries in mortality and morbidity, the main outcomes associated
      with ARTIs. This definition still applies 20 years later, when the introduction
      of new and safe antibiotics and vaccines has certainly contributed to controlling
      the most life-threatening ARTIs, but has not had a major impact on viral ARTIs in
      paediatric age. One functional approach to preventing and treating ARTIs is non
      specifically increasing the immune response or enhancing the children's innate
      defence mechanisms. Different kinds of biologically active substances--called
      immunostimulants--of natural and synthetic origins and with different mechanisms
      of action have been introduced in some countries for the prevention of ARTIs in
      children. Recently, research focused on one of these compounds, Pidotimod, has
      attempted to better clarify and define its mechanisms of action both in vitro and
      in vivo. In this paper, we critically examine the most recent findings on
      Pidotimod. Certainly the improvement of research methodology in the last 20 years
      and the acquired knowledge in various fields of clinical immunology should be the
      starting point for research on Pidotimod. Preclinical research will be essential
      to better understand the mechanisms of action of this compound. However, in vivo
      studies, especially randomised control trials, will be necessary to establish the
      real efficacy of Pidotimod in the prevention of ARTIs in paediatric age.

PMID- 24314103
TI  - Is the Bahasa Malaysia version of the Montreal Cognitive Assessment (MoCA-BM) a
      better instrument than the Malay version of the Mini Mental State Examination (M
      MMSE) in screening for mild cognitive impairment (MCI) in the elderly?
AB  - INTRODUCTION: Mild Cognitive Impairment (MCI) is a known precursor to Alzheimer
      disease, yet there is a lack of validated screening instruments for its detection
      among the Malaysian elderly. OBJECTIVE: To compare the Bahasa Malaysia version of
      the Montreal Cognitive Assessment (MoCA-BM) with the Malay version of the Mini
      Mental State Examination (M-MMSE) in the detection of MCI among the Malaysian
      elderly. METHODOLOGY: This is a cross-sectional study conducted at the primary
      care centre of Universiti Kebangsaan Malaysia, Kuala Lumpur from December 2011 to
      mid-January 2012. Subjects aged 60 and above were recruited using systematic
      sampling method. Cut-off scores of 22/23 for MoCA-BM and 25/26 for M-MMSE were
      adopted. Kappa value and Pearson's correlation coefficient were used to ascertain
      the correlation between MOCA-BM and M-MMSE. Data were analysed using Mann-Whitney
      and Chi Square tests. RESULTS: The mean age of the 180 subjects enrolled was 65.3
      years (SD=5.4). They had a median of 6 years (IqR 25-75=5-11) total formal
      education. The prevalence of MCI using MoCA-BM and M-MMSE was 55.6% and 32.8%
      respectively. The odds of developing MCI were 1.153 (95% CI=1.055, 1.261; p<0.05)
      for every 1 year increase in age, 0.813 (95% CI=0.690, 0.959; p<0.05) with every
      extra year of education. Increasing age and lower education level were
      significantly associated with MCI. The MoCA-BM showed good internal consistency
      with Cronbach's alpha of 0.80. It had moderate correlation with M-MMSE (Pearson
      correlation coefficient=0.770, p<0.001) and moderate agreement for detecting MCI
      with Kappa values of 0.497 (p<0.001). CONCLUSION: The prevalence of MCI was
      higher using MoCA-BM compared to M-MMSE. Both instruments showed moderate
      concordance for screening MCI with correlation of their scores.

PMID- 24314104
TI  - A fifth major genetic group among honeybees revealed in Syria.
AB  - BACKGROUND: Apiculture has been practiced in North Africa and the Middle-East
      from antiquity. Several thousand years of selective breeding have left a mosaic
      of Apis mellifera subspecies in the Middle-East, many uniquely adapted and
      survived to local environmental conditions. In this study we explore the genetic
      diversity of A. mellifera from Syria (n = 1258), Lebanon (n = 169) and Iraq (n =
      35) based on 14 short tandem repeat (STR) loci in the context of reference
      populations from throughout the Old World (n = 732). RESULTS: Our data suggest
      that the Syrian honeybee Apis mellifera syriaca occurs in both Syrian and
      Lebanese territories, with no significant genetic variability between respective
      populations from Syria and Lebanon. All studied populations clustered within a
      new fifth independent nuclear cluster, congruent with an mtDNA Z haplotype
      identified in a previous study. Syrian honeybee populations are not associated
      with Oriental lineage O, except for sporadic introgression into some populations
      close to the Turkish and Iraqi borders. Southern Syrian and Lebanese populations
      demonstrated high levels of genetic diversity compared to the northern
      populations. CONCLUSION: This study revealed the effects of foreign queen
      importations on Syrian bee populations, especially for the region of Tartus,
      where extensive introgression of A. m. anatolica and/or A. m. caucasica alleles
      were identified. The policy of creating genetic conservation centers for the
      Syrian subspecies should take into consideration the influence of the oriental
      lineage O from the northern Syrian border and the large population of genetically
      divergent indigenous honeybees located in southern Syria.

PMID- 24314105
TI  - Tobacco seeds expressing feedback-insensitive cystathionine gamma-synthase
      exhibit elevated content of methionine and altered primary metabolic profile.
AB  - BACKGROUND: The essential sulfur-containing amino acid methionine plays a vital
      role in plant metabolism and human nutrition. In this study, we aimed to
      elucidate the regulatory role of the first committed enzyme in the methionine
      biosynthesis pathway, cystathionine gamma-synthase (CGS), on methionine
      accumulation in tobacco seeds. We also studied the effect of this manipulation on
      the seed's metabolism. RESULTS: Two forms of Arabidopsis CGS (AtCGS) were
      expressed under the control of the seeds-specific promoter of legumin B4:
      feedback-sensitive F-AtCGS (LF seeds), and feedback-insensitive T-AtCGS (LT
      seeds). Unexpectedly, the soluble content of methionine was reduced significantly
      in both sets of transgenic seeds. Amino acids analysis and feeding experiments
      indicated that although the level of methionine was reduced, the flux through its
      synthesis had increased. As a result, the level of protein-incorporated
      methionine had increased significantly in LT seeds by up to 60%, but this was not
      observed in LF seeds, whose methionine content is tightly regulated. This
      increase was accompanied by a higher content of other protein-incorporated amino
      acids, which led to 27% protein content in the seeds although this was
      statistically insignificantly. In addition, the levels of reducing sugars
      (representing starch) were slightly but significantly reduced, while that of oil
      was insignificantly reduced. To assess the impact of the high expression level of
      T-AtCGS in seeds on other primary metabolites, metabolic profiling using GC-MS
      was performed. This revealed significant alterations to the primary seed
      metabolism manifested by a significant increase in eight annotated metabolites
      (mostly sugars and their oxidized derivatives), while the levels of 12 other
      metabolites were reduced significantly in LT compared to wild-type seeds.
      CONCLUSION: Expression of T-AtCGS leads to an increase in the level of total Met,
      higher contents of total amino acids, and significant changes in the levels of 20
      annotated metabolites. The high level of oxidized metabolites, the two stress
      associated amino acids, proline and serine, and low level of glutathione suggest
      oxidative stress that occurs during LT seed development. This study provides
      information on the metabolic consequence of increased CGS activity in seeds and
      how it affects the seed's nutritional quality.

PMID- 24314107
TI  - Physical impaction injury effects on bacterial cells during spread plating
      influenced by cell characteristics of the organisms.
AB  - AIMS: To understand the factors that contribute to the variations in colony
      forming units (CFU) in different bacteria during spread plating. METHODS AND
      RESULTS: Employing a mix culture of vegetative cells of ten organisms varying in
      cell characteristics (Gram reaction, cell shape and cell size), spread plating to
      the extent of just drying the agar surface (50-60 s) was tested in comparison
      with the alternate spotting-and-tilt-spreading (SATS) approach where 100 MUl
      inoculum was distributed by mere tilting of plate after spotting as 20-25
      microdrops. The former imparted a significant reduction in CFU by 20% over the
      spreader-independent SATS approach. Extending the testing to single organisms,
      Gram-negative proteobacteria with relatively larger cells (Escherichia,
      Enterobacter, Agrobacterium, Ralstonia, Pantoea, Pseudomonas and Sphingomonas
      spp.) showed significant CFU reduction with spread plating except for slow
      growing Methylobacterium sp., while those with small rods (Xenophilus sp.) and
      cocci (Acinetobacter sp.) were less affected. Among Gram-positive nonspore
      formers, Staphylococcus epidermidis showed significant CFU reduction while
      Staphylococcus haemolyticus and actinobacteria (Microbacterium,
      Cellulosimicrobium and Brachybacterium spp.) with small rods/cocci were
      unaffected. Vegetative cells of Bacillus pumilus and B. subtilis were generally
      unaffected while others with larger rods (B. thuringiensis, Brevibacillus,
      Lysinibacillus and Paenibacillus spp.) were significantly affected. A simulated
      plating study coupled with live-dead bacterial staining endorsed the chances of
      cell disruption with spreader impaction in afflicted organisms. CONCLUSIONS:
      Significant reduction in CFU could occur during spread plating due to physical
      impaction injury to bacterial cells depending on the spreader usage and the
      variable effects on different organisms are determined by Gram reaction, cell
      size and cell shape. The inoculum spreader could impart physical disruption of
      vegetative cells against a hard surface. SIGNIFICANCE AND IMPACT OF STUDY:
      Possibility of CFU reduction in sensitive organisms and the skewed selection of
      hardier organisms during spread plating, and the recommendation of SATS as an
      easier and safer alternative for CFU enumerations.

PMID- 24314106
TI  - A stone miner with both silicosis and constrictive pericarditis: case report and
      review of the literature.
AB  - BACKGROUND: The working environment of stone miners has been believed to cause
      their susceptibility to respiratory diseases. Silicosis is an occupational
      disease caused by exposure to crystalline silica dust which is marked by
      inflammation and scarring in the lung. The immune system boosted after the silica
      invasion led to self-damage and lay the foundation of silicosis pathogenesis.
      Silicosis coexisting with other diseases in one patient has been reported,
      however, was not reported to coexist with constrictive pericarditis. We, for the
      first time, reported a patient with silicosis and constrictive pericarditis and
      thought the immune response was probably the link between the two. CASE
      PRESENTATION: A 59-year-old Chinese stone miner complained of chest distress was
      found to have lung nodules which were found to be silica deposits by biopsy. This
      patient was also found to have constrictive pericarditis at the same time. Later
      surgical decortication cured his symptoms. CONCLUSION: We provided the first case
      having constrictive pericarditis concomitant with silicosis. A probable link
      between the two diseases was the immune response boosted by the silica deposits.

PMID- 24314108
TI  - Stabilization of memory States by stochastic facilitating synapses.
AB  - Bistability within a small neural circuit can arise through an appropriate
      strength of excitatory recurrent feedback. The stability of a state of neural
      activity, measured by the mean dwelling time before a noise-induced transition to
      another state, depends on the neural firing-rate curves, the net strength of
      excitatory feedback, the statistics of spike times, and increases exponentially
      with the number of equivalent neurons in the circuit. Here, we show that such
      stability is greatly enhanced by synaptic facilitation and reduced by synaptic
      depression. We take into account the alteration in times of synaptic vesicle
      release, by calculating distributions of inter-release intervals of a synapse,
      which differ from the distribution of its incoming interspike intervals when the
      synapse is dynamic. In particular, release intervals produced by a Poisson spike
      train have a coefficient of variation greater than one when synapses are
      probabilistic and facilitating, whereas the coefficient of variation is less than
      one when synapses are depressing. However, in spite of the increased variability
      in postsynaptic input produced by facilitating synapses, their dominant effect is
      reduced synaptic efficacy at low input rates compared to high rates, which
      increases the curvature of neural input-output functions, leading to wider
      regions of bistability in parameter space and enhanced lifetimes of memory
      states. Our results are based on analytic methods with approximate formulae and
      bolstered by simulations of both Poisson processes and of circuits of noisy
      spiking model neurons. 

PMID- 24314109
TI  - Natural history of Sanfilippo syndrome in Spain.
AB  - BACKGROUND: Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is
      caused by a deficiency in one of the four enzymes involved in the lysosomal
      degradation of heparan sulphate. Four MPS III types have been recognized,
      characterized by a large phenotypic heterogeneity. This is the first Spanish
      study describing the natural history of Sanfilippo patients (MPSIIIA, MPSIIIB and
      MPSIIIC), representing an essential step for understanding patient prognosis and
      for the establishment and application of future therapies. METHODS: This
      retrospective study aimed to establish the natural history of MPS III in Spain
      based on an extensive chronological data survey involving physicians and parents
      of 55 Spanish MPSIII patients. In addition to clinical description we report
      biochemical and molecular analysis already performed in the majority of cases.
      RESULTS: The most frequent subtype was MPS IIIA (62%). Symptoms before diagnosis
      were speech delay in 85%, followed by coarse facial features in 78%, and
      hyperactivity in 65% of cases at a mean age of 3 years old. The median age at
      clinical and biochemical diagnosis for each MPS III subtype were as follows: IIIA
      4.4 years (1.2 - 16 years), IIIB 3.1 years (1-29 years), and IIIC 6.3 years (3.4
      22 years).45% of patients developed epilepsy at a median age of 8.7 (2.5 - 37)
      years old.Age of death for MPS IIIA patients was 15 years (11.5 - 26
      years).Molecular analysis of our cohort reveals, as alluded to above, a great
      allelic heterogeneity in the three subtypes without clear genotype-phenotype
      correlations in most cases. CONCLUSION: MPS IIIA is the most frequent subtype in
      Spanish Sanfilippo patients. Diagnosing physicians should consider Sanfilippo
      syndrome in children with non-specific speech delay, behavioural abnormalities,
      and/or mild dysmorphic features. We stress the importance of establishing early
      diagnosis procedures as soon as possible so as to be able to determine future
      short-term enzymatic or gene therapy treatments that can change the prognosis of
      the disease.

PMID- 24314110
TI  - Provision and practice of specialist preterm labour clinics: a UK survey of
      practice.
AB  - OBJECTIVE: To identify the current status of specialist preterm labour (PTL)
      clinic provision and management within the UK. DESIGN: Postal survey of clinical
      practice. SETTING UK POPULATION: All consultant-led obstetric units within the
      UK. METHODS: A questionnaire was sent by post to all 210 NHS consultant-led
      obstetric units within the UK. Units that had a specialist PTL clinic were asked
      to complete a further 20 questions defining their protocol for risk
      stratification and management. MAIN OUTCOME MEASURES: Current practice in
      specialist preterm labour clinics. RESULTS: We have identified 23 specialist
      clinics; the most common indications for attendance were previous PTL (100%),
      preterm prelabour rupture of membranes (95%), two large loop excisions of the
      transformation zone (95%) or cone biopsy (95%). There was significant
      heterogeneity in the indications for and method of primary treatment for short
      cervix, with cervical cerclage used in 45% of units, progesterone in 18% of units
      and Arabin cervical pessary in 5%. A further 23% used multiple treatment
      modalities in combination. CONCLUSIONS: A significant heterogeneity in all topics
      surveyed suggests an urgent need for networking, more evidence-based guidelines
      and prospective comparative audits to ascertain the real impact of specialist PTL
      clinics on the reduction in preterm birth and its sequelae.

PMID- 24314111
TI  - Direct measurement of electrostatic fields using single Teflon nanoparticle
      attached to AFM tip.
AB  - A single 210-nm Teflon nanoparticle (sTNP) was attached to the vertex of a
      silicon nitride (Si3N4) atomic force microscope tip and charged via contact
      electrification. The charged sTNP can then be considered a point charge and used
      to measure the electrostatic field adjacent to a parallel plate condenser using
      30-nm gold/20-nm titanium as electrodes. This technique can provide a measurement
      resolution of 250/100 nm along the X- and Z-axes, and the minimum electrostatic
      force can be measured within 50 pN. PACS: 07.79.Lh, 81.16.-c, 84.37. + q. 

PMID- 24314113
TI  - Pregnancy rates for U.S. women continue to drop.
AB  - The pregnancy rate for U.S. women in 2009 was 102.1 per 1,000 women aged 15-44,
      the lowest level in 12 years; only the 1997 rate of 101.6 has been lower in the
      last 30 years. Rates for women under age 30 fell during 1990-2009, while rates
      for women aged 30 and over increased. Rates for teenagers reached historic lows
      in 2009, including rates for the three major race and Hispanic origin groups.
      Pregnancy rates have declined about 10% each for married and unmarried women
      since 1990. The birth rate for married women was 72% higher than the rate for
      unmarried women; the abortion rate for unmarried women was almost five times
      higher than the rate for married women. Pregnancy rates for women in the United
      States continued to decline in 2009, reaching the lowest level in 12 years (102.1
      per 1,000 women aged 15-44). This level is 12% below the 1990 peak (115.8). The
      estimated number of pregnancies dropped to 6,369,000 (4,131,000 live births,
      1,152,000 induced abortions, and 1,087,000 fetal losses). The drop in birth rates
      since 2007 has been well documented. However, it is important to examine the
      other outcomes of pregnancy to understand the full scope of current reproductive
      trends. The data in this report provide a comprehensive picture of pregnancies
      and pregnancy outcomes. Data on pregnancy outcomes by age, race and Hispanic
      origin, and marital status are presented using data from the National Vital
      Statistics System, the Abortion Surveillance System and Guttmacher Institute, and
      the National Survey of Family Growth (NSFG).

PMID- 24314114
TI  - Design of mini-barcode for catfishes for assessment of archival biodiversity.
AB  - Recovery of DNA barcode sequences is often challenging from the archived
      specimens. However, short fragments of DNA may be recovered, which would
      significantly improve many unresolved taxonomic conflicts. Here, we designed a
      mini-barcode for catfishes comprising several species and many cryptic taxa. We
      analysed a data set of 3048 publicly available COI barcode sequences representing
      547 worldwide catfish species and performed 152 628 interspecies comparisons. A
      significantly more positively correlated interspecies distance was detected with
      transversion (0.78, P < 0.001) than with transition (0.70, P < 0.001). This
      suggested that transversions were better diagnostics for species identification.
      In the aligned data set, two transversion-rich fragments (53 bp and 119 bp) were
      identified. Transition/transversion bias value was 1.04 in 53-bp fragment, 1.23
      in 119-bp fragment and 1.50 in full-length barcode. The interspecies distance
      with full-length barcode was 0.212 +/- 0.037, while that with 53-bp and 119-bp
      fragments was 0.325 +/- 0.039 and 0.218 +/- 0.045, respectively. Survey of 53-bp
      fragment showed a possibility of only 1144 barcodes, while that of 119-bp
      fragment showed >4 million barcodes. Thus, the 119-bp fragment is a viable mini
      barcode for catfishes comprising >3000 extant species. Experiment with 82
      archived catfishes showed successful recovery of this mini-barcode using the
      designed primer. The mini-barcode sequences showed species-specific similarity in
      the range of 98-100% with the global database. Therefore, survey of a
      transversion-rich fragment within the full-length barcode would be an ideal
      approach of mini-barcode design for biodiversity assessment.

PMID- 24314112
TI  - Cortical GABAergic neurons are more severely impaired by alkalosis than acidosis.
AB  - BACKGROUND: Acid-base imbalance in various metabolic disturbances leads to human
      brain dysfunction. Compared with acidosis, the patients suffered from alkalosis
      demonstrate more severe neurological signs that are difficultly corrected. We
      hypothesize a causative process that the nerve cells in the brain are more
      vulnerable to alkalosis than acidosis. METHODS: The vulnerability of GABAergic
      neurons to alkalosis versus acidosis was compared by analyzing their functional
      changes in response to the extracellular high pH and low pH. The neuronal and
      synaptic functions were recorded by whole-cell recordings in the cortical slices.
      RESULTS: The elevation or attenuation of extracellular pH impaired these
      GABAergic neurons in terms of their capability to produce spikes, their
      responsiveness to excitatory synaptic inputs and their outputs via inhibitory
      synapses. Importantly, the dysfunction of these active properties appeared
      severer in alkalosis than acidosis. CONCLUSIONS: The severer impairment of
      cortical GABAergic neurons in alkalosis patients leads to more critical neural
      excitotoxicity, so that alkalosis-induced brain dysfunction is difficultly
      corrected, compared to acidosis. The vulnerability of cortical GABAergic neurons
      to high pH is likely a basis of severe clinical outcomes in alkalosis versus
      acidosis.

PMID- 24314115
TI  - Intrasphenoidal encephalocele: an incidental finding in emergency department.
AB  - BACKGROUND: Basal encephaloceles are rare clinical entities. Intrasphenoidal
      encephalocele (ISE) is a rare form of basal encephalocele. The clinical
      presentation is often subtle and may remain undetected. Only a limited number of
      cases of ISE have been reported, mostly in middle-aged patients who presented
      with symptoms. Clinical diagnosis and management remain a challenge. Our case
      reports ISE as an incidental finding in a very elderly male patient. FINDINGS: We
      present a case of ISE discovered as an incidental finding in a 99-year-old male
      who presented to the emergency department (ED) after a fall from bed. The
      encephalocele was discovered in the evaluation of the computed tomography (CT)
      scan of the head. CONCLUSION: This is an incidental manifestation of a rare
      disease. It demonstrates that these encephaloceles may not manifest clinically or
      symptomatically as other reports have suggested.

PMID- 24314116
TI  - Traffic-related exposures and biomarkers of systemic inflammation, endothelial
      activation and oxidative stress: a panel study in the US trucking industry.
AB  - BACKGROUND: Experimental evidence suggests that inhaled particles from vehicle
      exhaust have systemic effects on inflammation, endothelial activation and
      oxidative stress. In the present study we assess the relationships of short-term
      exposures with inflammatory endothelial activation and oxidative stress biomarker
      levels in a population of trucking industry workers. METHODS: Blood and urine
      samples were collected pre and post-shift, at the beginning and end of a workweek
      from 67 male non-smoking US trucking industry workers. Concurrent measurements of
      microenvironment concentrations of elemental and organic carbon (EC & OC), and
      fine particulate matter (PM2.5) combined with time activity patterns allowed for
      calculation of individual exposures. Associations between daily and first and
      last-day average levels of exposures and repeated measures of intercellular and
      vascular cell adhesion molecule-1 (ICAM-1 & VCAM-1), interleukin 6 (IL-6) and C
      reactive protein (CRP) blood levels and urinary 8-Hydroxy-2'-Deoxyguanosine (8
      OHdG) were assessed using linear mixed effects models for repeated measures.
      RESULTS: There was a statistically significant association between first and last
      day average PM2.5 and 8-OHdG (21% increase, 95% CI: 2, 42%) and first and last
      day average OC and IL-6 levels (18% increase 95% CI: 1, 37%) per IQR in exposure.
      There were no significant findings associated with EC or associations suggesting
      acute cross-shift effects. CONCLUSION: Our findings suggest associations between
      weekly average exposures of PM2.5 on markers of oxidative stress and OC on IL-6
      levels.

PMID- 24314117
TI  - Analysis of sea-island cotton and upland cotton in response to Verticillium
      dahliae infection by RNA sequencing.
AB  - BACKGROUND: Cotton Verticillium wilt is a serious soil-borne vascular disease
      that causes great economic loss each year. However, due to the lack of resistant
      varieties of upland cotton, the molecular mechanisms of resistance to this
      disease, especially to the pathogen Verticillium dahliae, remain unclear.
      RESULTS: We used the RNA-seq method to research the molecular mechanisms of
      cotton defence responses to different races of Verticillium dahliae by comparing
      infected sea-island cotton and upland cotton. A total of 77,212 unigenes were
      obtained, and the unigenes were subjected to BLAST searching and annotated using
      the GO and KO databases. Six sets of digital gene expression data were mapped to
      the reference transcriptome. The gene expression profiles of cotton infected with
      Verticillium dahliae were compared to those of uninfected cotton; 44
      differentially expressed genes were identified. Regarding genes involved in the
      phenylalanine metabolism pathway, the hydroxycinnamoyl transferase gene (HCT) was
      upregulated in upland cotton whereas PAL, 4CL, CAD, CCoAOMT, and COMT were
      upregulated in sea-island cotton. Almost no differentially expressed genes in
      this pathway were identified in sea-island cotton and upland cotton when they
      were infected with V. dahliae V991 and V. dahliae D07038, respectively.
      CONCLUSIONS: Our comprehensive gene expression data at the transcription level
      will help elucidate the molecular mechanisms of the cotton defence response to V.
      dahliae. By identifying the genes involved in the defence response of each type
      of cotton to V. dahliae, our data not only provide novel molecular information
      for researchers, but also help accelerate research on genes involved in defences
      in cotton.

PMID- 24314118
TI  - AML1-ETO triggers epigenetic activation of early growth response gene l, inducing
      apoptosis in t(8;21) acute myeloid leukemia.
AB  - The t(8;21)(q22;q22) translocation is the most common chromosomal translocation
      in acute myeloid leukemia (AML), and it gives rise to acute myeloid gene 1 (AML1)
      myeloid transforming gene 8 (ETO)-positive AML, which has a relatively favorable
      prognosis. However, the molecular mechanism related to a favorable prognosis in
      AML1-ETO-positive AML is still not fully understood. Our results show that the
      AML1-ETO fusion protein triggered activation of early growth response gene l
      (EGR1) by binding at AML1-binding sites on the EGR1 promoter and, subsequently,
      recruiting acetyltransferase P300, which is known to acetylate histones. However,
      AML1-ETO could not recruit DNA methyltransferases and histone deacetylases;
      therefore, EGR1 expression was affected by histone acetylation but not by DNA
      methylation. Both transcription and translation of EGR1 were higher in AML1-ETO
      positive AML cell lines than in AML1-ETO-negative AML cell lines, owing to
      acetylation. Furthermore, when AML1-ETO-positive AML cell lines were treated with
      C646 (P300 inhibitor) and trichostatin A (histone deacetylase inhibitor), EGR1
      expression was significantly decreased and increased, respectively. In addition,
      treatment with 5-azacytidine (methyltransferase inhibitor) did not cause any
      significant change in EGR1 expression. Overexpression of EGR1 inhibited cell
      proliferation and promoted apoptosis, and EGR1 knockout promoted cell
      proliferation. Thus, EGR1 could be a novel prognostic factor for a favorable
      outcome in AML1-ETO-positive AML. The results of our study may explain the
      molecular mechanisms underlying the favorable prognosis in AML1-ETO-positive AML.

PMID- 24314119
TI  - Impact of yoga on blood pressure and quality of life in patients with
      hypertension - a controlled trial in primary care, matched for systolic blood
      pressure.
AB  - BACKGROUND: Medical treatment of hypertension is not always sufficient to achieve
      blood pressure control. Despite this, previous studies on supplementary
      therapies, such as yoga, are relatively few. We investigated the effects of two
      yoga interventions on blood pressure and quality of life in patients in primary
      health care diagnosed with hypertension. METHODS: Adult patients (age 20-80
      years) with diagnosed hypertension were identified by an electronic chart search
      at a primary health care center in southern Sweden. In total, 83 subjects with
      blood pressure values of 120-179/<=109 mmHg at baseline were enrolled. At
      baseline, the patients underwent standardized blood pressure measurement at the
      health care center and they completed a questionnaire on self-rated quality of
      life (WHOQOL-BREF). There were three groups: 1) yoga class with yoga instructor
      (n = 28); 2) yoga at home (n = 28); and 3) a control group (n = 27). The
      participants were matched at the group level for systolic blood pressure. After
      12 weeks of intervention, the assessments were performed again. At baseline a
      majority of the patients (92%) were on antihypertensive medication, and the
      patients were requested not to change their medication during the study. RESULTS:
      The yoga class group showed no improvement in blood pressure or self-rated
      quality of life, while in the yoga at home group there was a decline in diastolic
      blood pressure of 4.4 mmHg (p < 0.05) compared to the control group. Moreover,
      the yoga at home group showed significant improvement in self-rated quality of
      life compared to the control group (p < 0.05). CONCLUSIONS: A short yoga program
      for the patient to practice at home seems to have an antihypertensive effect, as
      well as a positive effect on self-rated quality of life compared to controls.
      This implies that simple yoga exercises may be useful as a supplementary blood
      pressure therapy in addition to medical treatment when prescribed by primary care
      physicians.

PMID- 24314120
TI  - Construction of a simple biocatalyst using psychrophilic bacterial cells and its
      application for efficient 3-hydroxypropionaldehyde production from glycerol.
AB  - Most whole cell biocatalysts have some problems with yields and productivities
      because of various metabolites produced as byproducts and limitations of
      substrate uptake. We propose a psychrophile-based simple biocatalyst for
      efficient bio-production using mesophilic enzymes expressed in psychrophilic
      Shewanella livingstonensis Ac10 cells whose basic metabolism was inactivated by
      heat treatment. The 45 degrees C heat-treated cells expressing lacZ showed
      maximum beta-galactosidase activity as well as chloroform/SDS-treated cells to
      increase membrane permeability. The fluorescent dye 5-cyano-2,3-ditolyl
      tetrazolium chloride staining indicated that most basic metabolism of Ac10 was
      lost by heat treatment at 45C for 10 min. The simple biocatalyst was applied for
      3-HPA production by using Klebsiella pneumoniae dhaB genes. 3-HPA was
      stoichiometrically produced with the complete consumption of glycerol at a high
      production rate of 8.85 mmol 3-HPA/g dry cell/h. The amount of 3-HPA production
      increased by increasing the concentrations of biocatalyst and glycerol.
      Furthermore, it could convert biodiesel-derived crude glycerol to 3-HPA. 

PMID- 24314121
TI  - Microbial populations and activities of mangrove, restinga and Atlantic forest
      soils from Cardoso Island, Brazil.
AB  - AIM: Mangroves provide a distinctive ecological environment that differentiates
      them from other ecosystems. This study deal to evaluate the frequency of
      microbial groups and the metabolic activities of bacteria and fungi isolated from
      mangrove, restinga and Atlantic forest soils. METHODS AND RESULTS: Soil samples
      were collected during the summer and winter at depths of 0-2, 2-5 and 5-10 cm.
      Except for fungi, the counts of the total, sporulating, Gram-negative,
      actinomycetes, nitrifying and denitrifying bacteria decreased significantly in
      the following order: Atlantic forest >mangrove > restinga. The counts of micro
      organisms decreased by 11 and 21% from the surface to the 2-5 and 5-10 cm layers,
      but denitrifying bacteria increased by 44 and 166%, respectively. A larger growth
      of micro-organisms was verified in the summer compared with the winter, except
      for actinomycetes and fungi. The average frequency of bacteria isolated from
      mangrove, restinga and Atlantic forest soils was 95, 77 and 78%, and 93, 90 and
      95% for fungi, respectively. Bacteria were amylolytic (33%), producers of acid
      phosphatase (79%) and solubilizers (18%) of inorganic phosphate. The proportions
      of fungi were 19, 90 and 27%. CONCLUSION: The mangrove soil studied had higher
      chemical characteristics than the Atlantic forest, but the high salinity may have
      restricted the growth of microbial populations. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Estimates of the microbial counts and activities were important to
      elucidate the differences of mangrove ecosystem from restinga and Atlantic
      forest.

PMID- 24314122
TI  - Interaction of prenatal maternal smoking, interleukin 13 genetic variants and DNA
      methylation influencing airflow and airway reactivity.
AB  - BACKGROUND: Asthma is characterized by airflow limitation and airway reactivity
      (AR). Interleukin-13 (IL-13) is involved in the pathogenesis of asthma. Two
      functional SNPs, rs20541 and rs1800925, of the IL-13 gene (IL13) have been
      frequently associated with asthma-related lung functions. However, genetic
      variation alone does not fully explain asthma risk. DNA-methylation (DNA-M) is an
      epigenetic mechanism that regulates gene expression and can be influenced by both
      environment and genetic variants. To explore the interplay of prenatal maternal
      smoking, genetic variants and DNA-M, we used a two-stage model: (1) identifying
      cytosine phosphate guanine (CpG) sites where DNA-M is influenced by the
      interaction between genetic variants and maternal smoking during pregnancy
      (conditional methQTL (methylation quantitative trait loci)); and (2) determining
      the effect of the interaction between DNA-M of CpG (from stage 1) and SNPs
      (modifying genetic variants; modGV) on airflow limitation and AR in 245 female
      participants of the Isle of Wight birth cohort. DNA-M was assessed using the
      Illumina Infinium HumanMethylation450 BeadChip. FINDINGS: Six CpG sites were
      analyzed in stage 1. DNA-M at cg13566430 was influenced by interaction of
      maternal smoking during pregnancy and rs20541. In stage 2, genotype at rs1800925
      interacted with DNA-M at cg13566430 significantly affecting airflow limitation (P
      = 0.042) and AR (P = 0.01). CONCLUSION: Both genetic variants and environment
      affect DNA-M. This study supports the proposed two-stage model (methQTL and
      modGV) to study genetic variants, environment and DNA-M interactions in asthma
      related lung function.

PMID- 24314123
TI  - Qualitative assessment of attributes and ease of use of the ELLIPTATM dry powder
      inhaler for delivery of maintenance therapy for asthma and COPD.
AB  - BACKGROUND: Medications for respiratory disorders including asthma and chronic
      obstructive pulmonary disease (COPD) are typically delivered to the lung by means
      of a handheld inhaler. Patient preference for and ability to use the inhaler may
      influence their adherence to maintenance therapy, and adherence may affect
      treatment outcomes. In this study, patient experience of using a dry powder
      inhaler (DPI), the ELLIPTATM DPI, in clinical trials of a new maintenance therapy
      for asthma and COPD was investigated. The ELLIPTA DPI has been designed to
      contain two separate blister strips from which inhalation powder can be
      delivered, and to be simple to use with a large, easy-to-read dose counter.
      METHODS: Semi-structured, in-depth, qualitative interviews were carried out 2-4
      weeks after patients had completed one of six phase IIIa clinical trials using
      the ELLIPTA DPI. Interview participants were asked about their satisfaction with
      various attributes of the inhaler and their preference for the ELLIPTA DPI
      relative to currently-prescribed inhalers, and responses were explored using an
      inductive content analysis approach. Participants also rated the performance of
      the inhaler on several criteria, using a subjective 1-10 scale. RESULTS:
      Participants with asthma (n = 33) and COPD (n = 42) reported high levels of
      satisfaction with the ELLIPTA DPI. It was frequently described as straightforward
      to operate and easy to use by interview participants. Ergonomic design,
      mouthpiece fit, and dose counter visibility and ease of interpretation emerged as
      frequently cited drivers of preference for the ELLIPTA DPI compared with their
      current prescribed inhaler. Of participants with asthma, 71% preferred the
      ELLIPTA DPI to DISKUSTM and 60% to metered dose inhalers. Of participants with
      COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHalerTM, and 85% to
      metered dose inhalers. Overall average performance scores were >9 (out of 10) in
      participants with asthma and COPD. CONCLUSION: The ELLIPTA DPI was associated
      with high patient satisfaction and was preferred to other inhalers by interview
      participants with asthma and COPD. The development of an inhaler that is regarded
      as easy and intuitive to use may have positive implications for adherence to
      therapy in asthma and COPD.

PMID- 24314124
TI  - A clinical study of the efficacy of a single session of individual exercise for
      depressive patients, assessed by the change in saliva free cortisol level.
AB  - BACKGROUND: The efficacy of physical exercise as an augmentation to
      pharmacotherapy with antidepressants for depressive patients has been documented.
      However, to clarify the effectiveness of exercise in the treatment of depression,
      it is necessary to distinguish the effect of the exercise itself from the effect
      of group dynamics. Furthermore, an objective measurement for estimation of the
      effect is needed. Previous reports adopted a series of group exercises as the
      exercise intervention and mainly psychometric instruments for the measurement of
      effectiveness. Therefore, this clinical study was done to examine the
      effectiveness of a single session of individual exercise on depressive symptoms
      by assessing the change in saliva free cortisol level, which reflects
      hypothalamic-pituitary-adrenocortical axis function that is disturbed in
      depressive patients. METHOD: Eighteen medicated patients, who met the DSM-IV-TR
      criteria for major depressive disorder, were examined for the change in saliva
      free cortisol levels and the change in subjective depressive symptoms before and
      after pedaling a bicycle ergometer for fifteen minutes. Within a month after the
      exercise session, participants conducted a non-exercise control session, which
      was sitting quietly at the same time of day as the exercise session. RESULTS:
      Depressed patients who participated in this study were in remission or in mild
      depressive state. However, they suffered chronic depression and had disturbed
      quality of life. The saliva free cortisol level and subjective depressive
      symptoms significantly decreased after the exercise session. Moreover, the
      changes in these variables were significantly, positively correlated. On the
      other hand, although the subjective depressive symptoms improved in the control
      session, the saliva free cortisol level did not change. CONCLUSION: For the first
      time in depressive patients, we were able to show a decrease in the saliva free
      cortisol level due to physical exercise, accompanied by the improvement of
      subjective depressive symptoms. This identified a possible influence of exercise
      on the hypothalamic-pituitary-adrenal axis in depression.These results suggest
      the utility of assessing the effect of physical exercise by saliva free cortisol
      level in depressive patients who suffer from bio-psycho-social disability.

PMID- 24314125
TI  - Integrin-linked kinase modulates longevity and thermotolerance in C. elegans
      through neuronal control of HSF-1.
AB  - Integrin-signaling complexes play important roles in cytoskeletal organization
      and cell adhesion in many species. Components of the integrin-signaling complex
      have been linked to aging in both Caenorhabditis elegans and Drosophila
      melanogaster, but the mechanism underlying this function is unknown. Here, we
      investigated the role of integrin-linked kinase (ILK), a key component of the
      integrin-signaling complex, in lifespan determination. We report that genetic
      reduction of ILK in both C. elegans and Drosophila increased resistance to heat
      stress, and led to lifespan extension in C. elegans without majorly affecting
      cytoskeletal integrity. In C. elegans, longevity and thermotolerance induced by
      ILK depletion was mediated by heat-shock factor-1 (HSF-1), a major
      transcriptional regulator of the heat-shock response (HSR). Reduction in ILK
      levels increased hsf-1 transcription and activation, and led to enhanced
      expression of a subset of genes with roles in the HSR. Moreover, induction of HSR
      related genes, longevity and thermotolerance caused by ILK reduction required the
      thermosensory neurons AFD and interneurons AIY, which are known to play a
      critical role in the canonical HSR. Notably, ILK was expressed in neighboring
      neurons, but not in AFD or AIY, implying that ILK reduction initiates cell
      nonautonomous signaling through thermosensory neurons to elicit a noncanonical
      HSR. Our results thus identify HSF-1 as a novel effector of the organismal
      response to reduced ILK levels and show that ILK inhibition regulates HSF-1 in a
      cell nonautonomous fashion to enhance stress resistance and lifespan in C.
      elegans.

PMID- 24314130
TI  - An adaptive process model of motor learning: insights for the teaching of motor
      skills.
AB  - This article presents an outline of a non-equilibrium model, in which motor
      learning is explained as a continuous process of stabilization and adaptation.
      The article also shows how propositions derived from this model have been tested,
      and discusses possible practical implications of some supporting evidence to the
      teaching of motor skills. The stabilization refers to a process of functional
      stabilization that is achieved through negative feedback mechanisms. Initially,
      inconsistent and incorrect responses are gradually reduced, leading to a spatial
      temporal patterning of the action. The adaptation is one in which new skills are
      formed from the reorganization of those already acquired through the flexibility
      of the system, reorganization of the skill structure, or self-organization. In
      order to provide learners with competency for adaptation, teachers should (a)
      guide students to learn motor skills taking into account that the stabilization
      of performance is just a transitory state that must be dismantled to achieve
      higher levels of complexity; (b) be clear which parts (micro) compose the skills
      and how they interact in order to form the whole (macro); (c) manipulate the
      skills in terms of their temporal, spatial, and/or spatiotemporal dimensions; (d)
      organize practice initially in a constant way, and then in a varied regimen
      (random) when the motor skills involve requirements of time and force; and,
      inversely for motor skills with spatial demands; and (e), provide a moderate
      frequency of feedback.

PMID- 24314126
TI  - Methodology for developing quality indicators for the care of older people in the
      Emergency Department.
AB  - BACKGROUND: Compared with younger people, older people have a higher risk of
      adverse health outcomes when presenting to emergency departments. As the
      population ages, older people will make up an increasing proportion of the
      emergency department population. Therefore it is timely that consideration be
      given to the quality of care received by older persons in emergency departments,
      and to consideration of those older people with special needs. Particular
      attention will be focused on important groups of older people, such as patients
      with cognitive impairment, residents of long term care and patients with
      palliative care needs. This project will develop a suite of quality indicators
      focused on the care of older persons in the emergency department. METHODS/DESIGN:
      Following input from an expert panel, an initial set of structural, process, and
      outcome indicators will be developed based on thorough systematic search in the
      scientific literature. All initial indicators will be tested in eight emergency
      departments for their validity and feasibility. Results of the data from the
      field studies will be presented to the expert panel at a second meeting. A suite
      of Quality Indicators for the older emergency department population will be
      finalised following a formal voting process. DISCUSSION: The predicted burgeoning
      in the number of older persons presenting to emergency departments combined with
      the recognised quality deficiencies in emergency department care delivery to this
      population, highlight the need for a quality framework for the care of older
      persons in emergency departments. Additionally, high quality of care is
      associated with improved survival & health outcomes of elderly patients. The
      development of well-selected, validated and economical quality indicators will
      allow appropriate targeting of resources (financial, education or quality
      management) to improve quality in areas with maximum potential for improvement.

PMID- 24314131
TI  - Ought-approach versus ought-avoidance: nonlinear effects on arousal under
      achievement situations.
AB  - The present study examines the dimensions of oughts under a nonlinear
      perspective. Ought-approach and ought-avoidance have been proposed as two
      different dimensions of oughts, which have an opposite effect on subjects'
      arousal level under achievement situation. The change in arousal level measured
      by heart rates per minute (HRPM) was modeled as cusp catastrophe by implementing
      the two dimensions of oughts as the control parameters: the ought-approach as the
      asymmetry and the ought-avoidance as the bifurcation factor. The cusp model was
      proved by far superior from the three alternative linear models and provided the
      empirical evidence that the two dimensions of oughts are distinct and are
      associated with different processes. The ought-avoidance dimension being the
      bifurcation factor acts in a destructive manner by introducing nonlinearity and
      uncertainty in the self-regulation process (with regard to HRPM). The
      interpretation of the model is provided and implications are discussed. 

PMID- 24314134
TI  - Duration and urgency of transfer in births planned at home and in freestanding
      midwifery units in England: secondary analysis of the birthplace national
      prospective cohort study.
AB  - BACKGROUND: In England, there is a policy of offering healthy women with
      straightforward pregnancies a choice of birth setting. Options may include home
      or a freestanding midwifery unit (FMU). Transfer rates from these settings are
      around 20%, and higher for nulliparous women. The duration of transfer is of
      interest because of the potential for delay in access to specialist care and is
      also of concern to women. We aimed to estimate the duration of transfer in births
      planned at home and in FMUs and explore the effects of distance and urgency on
      duration. METHODS: This was a secondary analysis of data collected in a national
      prospective cohort study including 27,842 'low risk' women with singleton, term,
      'booked' pregnancies, planning birth in FMUs or at home in England from April
      2008 to April 2010. We described transfer duration using the median and
      interquartile range, for all transfers and those for reasons defined as
      potentially urgent or non-urgent, and used cumulative distribution curves to
      compare transfer duration by urgency. We explored the effect of distance for
      transfers from FMUs and described outcomes in women giving birth within 60
      minutes of transfer. RESULTS: The median overall transfer time, from decision to
      transfer to first OU assessment, was shorter in transfers from home compared with
      transfers from FMUs (49 vs 60 minutes; p < 0.001). The median duration of
      transfers before birth for potentially urgent reasons (home 42 minutes, FMU 50
      minutes) was 8-10 minutes shorter compared with transfers for non-urgent reasons.
      In transfers for potentially urgent reasons, the median overall transfer time
      from FMUs within 20 km of an OU was 47 minutes, increasing to 55 minutes from
      FMUs 20-40 km away and 61 minutes in more remote FMUs. In women who gave birth
      within 60 minutes after transfer, adverse neonatal outcomes occurred in 1-2% of
      transfers. CONCLUSIONS: Transfers from home or FMU commonly take up to 60 minutes
      from decision to transfer, to first assessment in an OU, even for transfers for
      potentially urgent reasons. Most transfers are not urgent and emergencies and
      adverse outcomes are uncommon, but urgent transfer is more likely for nulliparous
      women.

PMID- 24314135
TI  - Caspase 3 activity in isolated fetal rat lung fibroblasts and rat periodontal
      ligament fibroblasts: cigarette smoke induced alterations.
AB  - BACKGROUND: Cigarette smoking is the leading cause of preventable death and has
      been implicated in pathogenesis of pulmonary, oral and systemic diseases. Smoking
      during pregnancy is a risk factor for the developing fetus and may be a major
      cause of infant mortality. Moreover, the oral cavity, and all cells within are
      the first to be exposed to cigarette smoke and may be a possible source for the
      spread of toxins to other organs of the body. Fibroblasts in general are
      morphologically heterogeneous connective tissue cells with diverse functions.
      Apoptosis or programmed cell death is a crucial process during embryogenesis and
      for the maintenance of homeostasis throughout life. Deregulation of apoptosis has
      been implicated in abnormal lung development in the fetus and disease progression
      in adults. Caspases are proteases which belong to the family of cysteine aspartic
      acid proteases and are key components for downstream amplification of
      intracellular apoptotic signals. Of 14 known caspases, caspase-3 is the key
      executioner of apoptosis. In the present study we explored the hypothesis that
      cigarette smoke (CS) extract activates caspase-3 in two types of fibroblasts,
      both of which would be exposed directly to cigarette smoke, isolated fetal rat
      lung fibroblasts and adult rat periodontal ligament (PDL) fibroblasts. METHODS:
      Isolated fetal rat lung fibroblasts and adult PDLs were used. Cells were exposed
      to different concentrations of CS for 60 min. Caspase-3 activity and its
      inhibition by Z-VAD-fmk were measured by caspase-3 fluorometric assay. The effect
      of CSE on cellular viability was measured using the MTT formazan assay. Caspase-3
      expression was detected by western blot analysis and cellular localization of
      caspase-3 was determined by immunofluorescence using fluorescence microscopy.
      RESULTS: It was observed in fetal rat lung fibroblast cells that CSE extract
      significantly (p<0.05) increased caspase-3 activity and decrease cell
      proliferation. However, no significant changes in activity or viability were
      observed in PDLs. CONCLUSIONS: This indicates CS activates caspase-3 the key
      regulatory point in apoptosis in fetal rat lung fibroblast cells suggesting that
      smoking during pregnancy may alter the developmental program of fetal lung,
      jeopardizing the establishment of critical cellular mechanisms necessary to
      expedite pulmonary maturation at birth.of critical cellular mechanisms necessary
      to expedite pulmonary maturation at birth.

PMID- 24314136
TI  - In vitro antifungal activity of farnesyltransferase inhibitors against clinical
      isolates of Aspergillus and Candida.
AB  - BACKGROUND: Protein farnesylation is an important tosttranslational modification
      in fungi. We evaluated the antifungal activity of two farnesyltransferase
      inhibitors against clinical isolates of Aspergillus and Candida. METHODS: Disk
      diffusion assay and broth microdilution assay were used to determine the
      antifungal susceptibility of two farnesyltransferase inhibitors (manumycin A and
      tipifarnib) against clinical isolates of Aspergillus and Candida. RESULTS: Disk
      diffusion assay demonstrated both agents had activity against Aspergillus and
      Candida. The minimal inhibitory concentration (MIC) ranges for manumycin A
      against Aspergillus and Candida were 200 to 400 MUM and 13 to >25 MUM,
      respectively. Unfortunately, the MIC were vastly higher than the concentrations
      that inhibit the proliferation and viability of mammalian cells. The MICs of
      tipifarnib against Aspergillus and Candida were >1600 MUM. CONCLUSION: The
      outcome of present study showed that farnesyltransferase inhibitors have activity
      against Aspergillus and Candida. This suggests that farnesyltransferase may be
      used as anifungal target in designing and developing new drugs.

PMID- 24314137
TI  - Targeting the hydrophobic pocket of autotaxin with virtual screening of
      inhibitors identifies a common aromatic sulfonamide structural motif.
AB  - Modulation of autotaxin (ATX), the lysophospholipase D enzyme that produces
      lysophosphatidic acid, with small-molecule inhibitors is a promising strategy for
      blocking the ATX-lysophosphatidic acid signaling axis. Although discovery
      campaigns have been successful in identifying ATX inhibitors, many of the
      reported inhibitors target the catalytic cleft of ATX. A recent study provided
      evidence for an additional inhibitory surface in the hydrophobic binding pocket
      of ATX, confirming prior studies that relied on enzyme kinetics and differential
      inhibition of substrates varying in size. Multiple hits from previous high
      throughput screening for ATX inhibitors were obtained with aromatic sulfonamide
      derivatives interacting with the hydrophobic pocket. Here, we describe the
      development of a ligand-based strategy and its application in virtual screening,
      which yielded novel high-potency inhibitors that target the hydrophobic pocket of
      ATX. Characterization of the structure-activity relationship of these new
      inhibitors forms the foundation of a new pharmacophore model of the hydrophobic
      pocket of ATX.

PMID- 24314138
TI  - Cost-effectiveness analysis of azacitidine in the treatment of high-risk
      myelodysplastic syndromes in Spain.
AB  - BACKGROUND: The objective of the study was to analyse whether azacitidine is a
      cost-effective option for the treatment of myelodysplastic syndrome in the
      Spanish setting compared with conventional care regimens, including best
      supportive care, low dose chemotherapy and standard dose chemotherapy. METHODS: A
      life-time Markov model was constructed to evaluate the cost-effectiveness of
      azacitidine compared with conventional care regimens. The health states modelled
      were: myelodysplastic syndrome, acute myeloid leukemia and death. Variables
      measured included survival rates, progression probabilities and quality of life
      indicators. Resource use and cost data reflect the Spanish context. The analysis
      was performed from the Spanish National Health System perspective, discounting
      both costs (in 2012 euros) and future effects at 3%. The time horizon considered
      was end-of-life. Results were expressed in cost per quality-adjusted life-year
      gained and cost per life-year gained and compared with cost-effectiveness
      thresholds. RESULTS: According to the current use of each conventional care
      regimens options in Spain, azacitidine resulted in ?34,673 per quality-adjusted
      life-year gained (?28,891 per life-year gained) with an increase of 1.89 in
      quality-adjusted life-years (2.26 in life-years). Azacitidine was superior to
      best supportive care and low dose chemotherapy in terms of quality-adjusted life
      years gained, 1.82 and 2.03, respectively (life-years 2.16 vs. best supportive
      care, 2.39 vs. low dose chemotherapy). Treatment with azacitidine resulted in
      longer survival time and thus longer treatment time and lifetime costs. The
      incremental cost-effectiveness ratio was ?39,610 per quality-adjusted life-year
      gained vs. best supportive care and ?30,531 per quality-adjusted life-year gained
      vs. low dose chemotherapy (?33,111 per life-year gained vs. best supportive care
      and ?25,953 per life-year gained vs. low dose chemotherapy). CONCLUSIONS: The
      analysis showed that the use of azacitidine in the treatment of high-risk
      myelodysplastic syndrome is a cost-effective option compared with conventional
      care regimen options used in the Spanish setting and had an incremental cost
      effectiveness ratio within the range of the thresholds accepted by health
      authorities.

PMID- 24314140
TI  - AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating
      mobilization of hematopoietic stem/progenitor cells.
AB  - Inhibition of an increase of osteoclasts has become the most important treatment
      for osteoporosis. The CXCR4 antagonist, AMD3100, plays an important role in the
      mobilization of osteoclast precursors within bone marrow (BM). However, the
      actual therapeutic impact of AMD3100 in osteoporosis has not yet been
      ascertained. Here we demonstrate the therapeutic effect of AMD3100 in the
      treatment of ovariectomy-induced osteoporosis in mice. We found that treatment
      with AMD3100 resulted in direct induction of release of SDF-1 from BM to blood
      and mobilization of hematopoietic stem/progenitor cells (HSPCs) in an
      osteoporosis model. AMD3100 prevented bone density loss after ovariectomy by
      mobilization of HSPCs, suggesting a therapeutic strategy to reduce the number of
      osteoclasts on bone surfaces. These findings support the hypothesis that
      treatment with AMD3100 can result in efficient mobilization of HSPCs into blood
      through direct blockade of the SDF-1/CXCR4 interaction in BM and can be
      considered as a potential new therapeutic intervention for osteoporosis.

PMID- 24314139
TI  - Reprogramming of lysosomal gene expression by interleukin-4 and Stat6.
AB  - BACKGROUND: Lysosomes play important roles in multiple aspects of physiology, but
      the problem of how the transcription of lysosomal genes is coordinated remains
      incompletely understood. The goal of this study was to illuminate the
      physiological contexts in which lysosomal genes are coordinately regulated and to
      identify transcription factors involved in this control. RESULTS: As
      transcription factors and their target genes are often co-regulated, we performed
      meta-analyses of array-based expression data to identify regulators whose mRNA
      profiles are highly correlated with those of a core set of lysosomal genes. Among
      the ~50 transcription factors that rank highest by this measure, 65% are involved
      in differentiation or development, and 22% have been implicated in interferon
      signaling. The most strongly correlated candidate was Stat6, a factor commonly
      activated by interleukin-4 (IL-4) or IL-13. Publicly available chromatin
      immunoprecipitation (ChIP) data from alternatively activated mouse macrophages
      show that lysosomal genes are overrepresented among Stat6-bound targets.
      Quantification of RNA from wild-type and Stat6-deficient cells indicates that
      Stat6 promotes the expression of over 100 lysosomal genes, including hydrolases,
      subunits of the vacuolar H+ ATPase and trafficking factors. While IL-4 inhibits
      and activates different sets of lysosomal genes, Stat6 mediates only the
      activating effects of IL-4, by promoting increased expression and by neutralizing
      undefined inhibitory signals induced by IL-4. CONCLUSIONS: The current data
      establish Stat6 as a broadly acting regulator of lysosomal gene expression in
      mouse macrophages. Other regulators whose expression correlates with lysosomal
      genes suggest that lysosome function is frequently re-programmed during
      differentiation, development and interferon signaling.

PMID- 24314142
TI  - BI-1 enhances Fas-induced cell death through a Na+/H+-associated mechanism.
AB  - The role of Bax inhibitor-1 (BI-1) in the protective mechanism against apoptotic
      stimuli has been studied; however, as little is known about its role in death
      receptor-mediated cell death, this study was designed to investigate the effect
      of BI-1 on Fas-induced cell death, and the underlying mechanisms. HT1080
      adenocarcinoma cells were cultured in high concentration of glucose media and
      transfected with vector alone (Neo cells) or BI-1-vector (BI-1 cells), and
      treated with Fas. In cell viability, apoptosis, and caspase-3 analyses, the BI-1
      cells showed enhanced sensitivity to Fas. Fas significantly decreased cytosolic
      pH in BI-1 cells, compared with Neo cells, and this decrease correlated with BI-1
      oligomerization, mitochondrial Ca2+ accumulation, and significant inhibition of
      sodium-hydrogen exchanger (NHE) activity. Compared with Neo cells, a single
      treatment of BI-1 cells with the NHE inhibitor EIPA or siRNA against NHE
      significantly increased cell death, which suggests that the viability of BI-1
      cells is affected by the maintenance of intracellular pH homeostasis through NHE.

PMID- 24314141
TI  - Inhibition of mouse SP2/0 myeloma cell growth by the B7-H4 protein vaccine.
AB  - B7-H4 is a member of B7 family of co-inhibitory molecules and B7-H4 protein is
      found to be overexpressed in many human cancers and which is usually associated
      with poor survival. In this study, we developed a therapeutic vaccine made from a
      fusion protein composed of a tetanus toxoid (TT) T-helper cell epitope and human
      B7-H4IgV domain (TT-rhB7-H4IgV). We investigated the anti-tumor effect of the TT
      rhB7-H4IgV vaccine in BALB/c mice and SP2/0 myeloma growth was significantly
      suppressed in mice. The TT-rhB7-H4IgV vaccine induced high-titer specific
      antibodies in mice. Further, the antibodies induced by TT-rhB7-H4IgV vaccine were
      capable of depleting SP2/0 cells through complement-dependent cytotoxicity (CDC)
      in vitro. On the other hand, the poor cellular immune response was irrelevant to
      the therapeutic efficacy. These results indicate that the recombinant TT-rhB7
      H4IgV vaccine might be a useful candidate of immunotherapy for the treatment of
      some tumors associated with abnormal expression of B7-H4.

PMID- 24314143
TI  - Parthenolide inhibits osteoclast differentiation and bone resorbing activity by
      down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated
      osteoclastogenesis.
AB  - Parthenolide, a natural product derived from Feverfew, prevents septic shock and
      inflammation. We aimed to identify the effects of parthenolide on the RANKL
      (receptor activator of NF-kappaB ligand)-induced differentiation and bone
      resorbing activity of osteoclasts. In this study, parthenolide dose-dependently
      inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence
      of cytotoxicity and the phosphorylation of p38, ERK, and IkappaB, as well as
      IkappaB degradation by RANKL treatment. Parthenolide suppressed the expression of
      NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs.
      Furthermore, parthenolide down-regulated the stability of c-Fos protein, but
      could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in
      BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast
      differentiation. Parthenolide also inhibited the bone resorbing activity of
      mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving
      activity of osteoclast by RANKL, suggesting its potential therapeutic value for
      bone destructive disorders associated with osteoclast-mediated bone resorption.

PMID- 24314144
TI  - Glucose regulated protein 78 promotes cell invasion via regulation of uPA
      production and secretion in colon cancer cells.
AB  - Glucose regulated protein 78 (GRP78) is frequently highly expressed in tumor
      cells, contributing to the acquisition of several phenotypic cancer hallmarks.
      GRP78 expression is also positively correlated with tumor metastasis, and
      promotes hepatocellular carcinoma cell invasion via increasing cell motility,
      however, other mechanisms involving the prometastatic roles of GRP78 remain to be
      elucidated. Here we report that forced GRP78 expression promotes colon cancer
      cell migration and invasion through upregulating MMP-2, MMP-9 and especially uPA
      production. These effects of GRP78 are mediated by enhancing the activation of
      beta-catenin signaling. Interestingly, we identify that GRP78 interacts with uPA
      both in the cells and in the culture medium, suggesting that GRP78 protein is
      likely to directly facilitate uPA secretion via protein-protein interaction.
      Taken together, our findings demonstrate for the first time that besides
      stimulation of cell motility, GRP78 can act by increasing proteases production to
      promote tumor cell invasion.

PMID- 24314146
TI  - Is the population of Crotalus durissus (Serpentes, Viperidae) expanding in
      Brazil?
AB  - Crotalus durissus are found from Mexico to northern Argentina in a highly
      disjunct distribution. According to some studies, this species is prone to occupy
      areas disturbed by human activities and floods comprise a plausible method of
      dispersal as inferred for some North American rattlesnakes. Based on the
      literature, it seems plausible that Crotalus durissus expanded their natural
      distribution in Brazil due to floods, but only in a few municipalities in Rio de
      Janeiro State. Data entries of Butantan Institute, in Sao Paulo, Brazil, from
      1998 to 2012 show a declining tendency of snakes brought by donors. In addition,
      research shows no evidence of Crotalus durissus being an expanding species in the
      Brazilian territory. 

PMID- 24314145
TI  - Predictive diagnosis of endometrial hyperplasia and personalized therapeutic
      strategy in women of fertile age.
AB  - INTRODUCTION: Endometrial hyperplasia has a high risk for malignant
      transformation and relapses; existing mini-invasive treatments may lead to
      irrevocable endometrium destruction. The aims were to analyze receptor systems in
      endometrial hyperplasia, to evaluate the capabilities of ultrasonography,
      sonoelastography for diagnosis and treatment control, and to develop treatment
      algorithm. MATERIALS AND METHODS: We included 313 women (20-45 years), assessed
      into the following: group 1 (n = 112) with glandular cystic hyperplasia, group 2
      (n = 98) endometrial polyps, and group 3 (n = 103) atypical hyperplasia; and 82
      controls who have undergone hysteroscopy before in vitro fertilization in tubal
      origin infertility were also included. Patients underwent clinical examination,
      transvaginal ultrasound, immunohistochemical study, and hormonal
      therapy/hysteroresectoscopy. RESULTS: In patients with glandular hyperplasia, we
      registered increase of endometrium estrogen receptors (75.6% in the epithelium
      and 30.9% in the stroma; in controls, 43.3% and 29.6%, respectively); in polyps,
      there was a significant estrogen receptor increase in the stroma (48.2% vs 29.6%
      in controls), and in atypical hyperplasia, progesterone receptors significantly
      increased in the stroma. Ki-67 increased (40% to 50%) in the epithelium without
      changes in the stroma. Ultrasound has a sensitivity of 96% and a specificity of
      85% for early detection of endometrial pathology and prediction outcome of
      intervention, and sonoelastography has a sensitivity of 91% and a specificity of
      83% for polyp diagnosis. Personalized treatment was effective in 88.8%, relapse
      was diagnosed in 11.2% after 6 months, and conservative treatment of atypical
      hyperplasia was effective in 45%: in 25.8%, ablative hysteroresectoscopy was
      performed, while in 22.6% with comorbidities, hystero/oophorectomies were
      performed. CONCLUSIONS: The evaluation of receptor status with ultrasound data in
      patients with endometrial hyperplasia allows for a clear definition of the
      treatment policy, avoidance of relapse, treatment optimization, and observation
      of such patients.

PMID- 24314147
TI  - Synergistic effect of 5-HT2A receptor gene and MAOA gene on the negative emotion
      of patients with depression.
AB  - OBJECTIVE: To analyse the synergistic effect of polymorphism of the tandem repeat
      sequence u-VNTR of 5-hydroxytryptamine 2A (5-HT2A) receptor gene and monoamine
      oxidase A (MAOA) gene on the negative emotion in frontal lobe of patients with
      depression through functional magnetic resonance imaging (fMRI) technique.
      METHODS: Functional magnetic resonance imaging scanning was performed for 72
      patients with depression and 70 gender, age-matched healthy people with physical
      examination under negative emotion recognition task. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method was adopted to analyse
      genotype. The superior, middle and inferior gyrus of bilateral frontal lobe was
      regarded as the brain region of interest, and then the difference of activation
      intensity in frontal lobe subregion between control groups and patient groups
      with different genotypes, and the interaction between the two kinds of
      polymorphism were compared. RESULTS: The activation intensity in right frontal
      middle gyrus of patients with CC genotype increased obviously compared with TT
      and TC genotype patient groups and TT genotype control group (P<0.01); the
      activation intensity in right frontal inferior gyrus of patients with CC genotype
      increased obviously compared with TT and TC genotype patient groups and control
      groups (P<0.01); the activation intensity in right frontal middle gyrus and left
      frontal inferior gyrus of patients with MAOA high-activity genotype increased
      obviously compared with patient and control groups with MAOA low-activity
      genotype (P<0.01). In sum, there existed synergistic effect of the two genotypes
      on the activation abnormality of negative emotion recognition in right frontal
      middle gyrus (F = 6.18, P = 0.029). The negative activation in right frontal
      middle gyrus of patients with CC+H genotypes increased most obviously (P<0.05).
      CONCLUSION: The frontal abnormality of patients with depression had certain 5-HT
      genetic basis, and 5-HT2A receptor CC allele and MAOA-H genotype had synergistic
      effect on the activity abnormality when recognizing negative emotion in right
      frontal middle gyrus of patients with depression.

PMID- 24314149
TI  - Bacterial viability differentially influences the immunomodulatory capabilities
      of potential host-derived probiotics in the intestinal epithelial cells of
      Atlantic cod Gadus morhua.
AB  - AIM: This study explored the effect of heat inactivation on the immunomodulatory
      capabilities of two potential host-derived probiotics (GP21 and GP12) on the
      intestinal epithelial cells (IEPC) derived from Atlantic cod. METHODS AND
      RESULTS: The cells were isolated from the four segments of the gut, namely
      anterior intestine (AI), mid-intestine (MI), posterior intestine (PI) and rectum
      (RC). The IEPC cultures were exposed to live or heat-inactivated form of GP21 and
      GP12 for 24 h. The expression profiles of bacterial defence genes and cytokine
      genes in the probiotics-exposed IEPCs showed differential patterns. Heat
      inactivation did not drastically affect the immunomodulatory properties of the
      probiotics, and this was explicitly typified by the stimulated expression of g
      type lysozyme, hepcidin, transferrin and metallothionein in both forms of the
      bacteria. There was no distinct expression pattern of the interleukin genes
      during bacterial exposure. This was in contrast to the chemokines where the
      expression of these genes in IEPCs was down-regulated upon exposure to the heat
      inactivated probiotics. Although heat inactivation did not drastically affect the
      immunomodulatory capabilities of the probiotics, the live form elicited higher
      immune responses in the IEPCs in most cases. CONCLUSION: This study showed that
      bacterial viability was a contributing influence, but not a major limiting factor
      on the immune-related functions of the host-derived probiotics in vitro.
      SIGNIFICANCE AND IMPACT OF THE STUDY: GP21 and GP12 are beneficial host-derived
      bacteria and could be utilized as candidate probiotics in cod aquaculture.

PMID- 24314148
TI  - Detecting cancer clusters in a regional population with local cluster tests and
      Bayesian smoothing methods: a simulation study.
AB  - BACKGROUND: There is a rising public and political demand for prospective cancer
      cluster monitoring. But there is little empirical evidence on the performance of
      established cluster detection tests under conditions of small and heterogeneous
      sample sizes and varying spatial scales, such as are the case for most existing
      population-based cancer registries. Therefore this simulation study aims to
      evaluate different cluster detection methods, implemented in the open source
      environment R, in their ability to identify clusters of lung cancer using real
      life data from an epidemiological cancer registry in Germany. METHODS: Risk
      surfaces were constructed with two different spatial cluster types, representing
      a relative risk of RR = 2.0 or of RR = 4.0, in relation to the overall background
      incidence of lung cancer, separately for men and women. Lung cancer cases were
      sampled from this risk surface as geocodes using an inhomogeneous Poisson
      process. The realisations of the cancer cases were analysed within small spatial
      (census tracts, N = 1983) and within aggregated large spatial scales
      (communities, N = 78). Subsequently, they were submitted to the cluster detection
      methods. The test accuracy for cluster location was determined in terms of
      detection rates (DR), false-positive (FP) rates and positive predictive values.
      The Bayesian smoothing models were evaluated using ROC curves. RESULTS: With
      moderate risk increase (RR = 2.0), local cluster tests showed better DR (for both
      spatial aggregation scales > 0.90) and lower FP rates (both < 0.05) than the
      Bayesian smoothing methods. When the cluster RR was raised four-fold, the local
      cluster tests showed better DR with lower FPs only for the small spatial scale.
      At a large spatial scale, the Bayesian smoothing methods, especially those
      implementing a spatial neighbourhood, showed a substantially lower FP rate than
      the cluster tests. However, the risk increases at this scale were mostly diluted
      by data aggregation. CONCLUSION: High resolution spatial scales seem more
      appropriate as data base for cancer cluster testing and monitoring than the
      commonly used aggregated scales. We suggest the development of a two-stage
      approach that combines methods with high detection rates as a first-line
      screening with methods of higher predictive ability at the second stage.

PMID- 24314150
TI  - Comparison of sample characteristics in two pregnancy cohorts: community-based
      versus population-based recruitment methods.
AB  - BACKGROUND: One of the biggest challenges for population health studies is the
      recruitment of participants. Questions that investigators have asked are "who
      volunteers for studies?" and "does recruitment method influence characteristics
      of the samples?" The purpose of this paper was to compare sample characteristics
      of two unrelated pregnancy cohort studies taking place in the same city, in the
      same time period, that employed different recruitment strategies, as well as to
      compare the characteristics of both cohorts to provincial and national statistics
      derived from the Maternity Experiences Survey (MES). METHODS: One pregnancy
      cohort used community-based recruitment (e.g. posters, pamphlets, interviews with
      community media and face-to-face recruitment in maternity clinics); the second
      pregnancy cohort used both community-based and population-based (a centralized
      system identifying pregnant women undergoing routine laboratory testing)
      strategies. RESULTS: The pregnancy cohorts differed in education, income,
      ethnicity, and foreign-born status (p < 0.01), but were similar for maternal age,
      BMI, and marital status. Compared to the MES, the lowest age, education, and
      income groups were under-represented, and the cohorts were more likely to be
      primiparous. CONCLUSIONS: The findings suggest that non-stratified strategies for
      recruitment of participants will not necessarily result in samples that reflect
      the general population, but can reflect the target population of interest.
      Attracting and retaining young, low resource women into urban studies about
      pregnancy may require alternate and innovative approaches.

PMID- 24314151
TI  - Protein quality control by Rer1p in the early secretory pathway: from mechanism
      to implication in Alzheimer's disease.
AB  - gamma-Secretase-mediated production of amyloid beta from the amyloid precursor
      protein is recognized as a central player in the neuropathogenesis of Alzheimer's
      disease (AD). One of the most peculiar features of this enzymatic activity is the
      fact that it targets transmembrane domains of mostly type I integral membrane
      proteins and thus manages to proteolyse peptide bonds within the hydrophobic
      lipid bilayers. In addition, gamma-secretase does not exert its activity solely
      towards amyloid precursor protein, but to an increasing number of membrane
      proteins, including Notch, cadherins, syndecans, and so on. Because of the
      requirement of intramembrane proteolysis for a plethora of signaling pathways and
      cellular processes during embryonic development and organ physiology, this enzyme
      has drawn a lot of attention in the past 20 years. gamma-Secretase is a
      multimeric transmembrane complex consisting of the catalytic presenilin,
      nicastrin, presenilin enhancer 2 (PEN2) and anterior-pharynx defective-1 (APH1)
      subunits. Proper assembly into functional complexes requires quality control
      mechanisms associated with the early biosynthetic compartments and allows mature
      complexes to transit to distal compartments where its activity is required. We
      previously identified Retrieval to ER protein 1 (Rer1p) as the first negative
      regulator of the stepwise assembly of gamma-secretase during endoplasmic
      reticulum-to-Golgi transport. We review here the state of the art on how Rer1p
      regulates complex assembly, particularly gamma-secretase, and evaluate the
      therapeutic potential of such regulatory processes in the context of AD. 

PMID- 24314152
TI  - No damage of joint cartilage of the lower limbs in an ultra-endurance athlete--an
      MRI-study.
AB  - BACKGROUND: Osteoarthritis is an increasing burden in an ageing population.
      Sports, especially when leading to an overstress of joints, is under suspicion to
      provoke or at least accelerate the genesis of osteoarthritis. We present the
      radiologic findings of a 49-years old ultra-endurance athlete with 35 years of
      training and competing, whose joints of the lower limbs were examined using three
      different types of magnetic resonance imaging, including a microscopic magnetic
      resonance imaging coil. To date no case report exists where an ultra-endurance
      athlete was examined such detailed regarding overuse-injuries of his joints. CASE
      PRESENTATION: A 49 years old, white, male ultra-endurance athlete reporting no
      pain during training and racing and with no significant injuries of the lower
      limbs in his medical history was investigated regarding signs of chronic damage
      or overuse injuries of the joints of his lower limbs. CONCLUSION: Despite the age
      of nearly 50 years and a training history of over 35 years, the athlete showed no
      signs of chronic damage or overuse injuries in the joints of his lower limbs.
      This leads to the conclusion that extensive sports and training does not
      compulsory lead to damages of the musculoskeletal system. This is a very
      important finding for all endurance-athletes as well as for their physicians.

PMID- 24314153
TI  - Stochastic flux analysis of chemical reaction networks.
AB  - BACKGROUND: Chemical reaction networks provide an abstraction scheme for a broad
      range of models in biology and ecology. The two common means for simulating these
      networks are the deterministic and the stochastic approaches. The traditional
      deterministic approach, based on differential equations, enjoys a rich set of
      analysis techniques, including a treatment of reaction fluxes. However, the
      discrete stochastic simulations, which provide advantages in some cases, lack a
      quantitative treatment of network fluxes. RESULTS: We describe a method for flux
      analysis of chemical reaction networks, where flux is given by the flow of
      species between reactions in stochastic simulations of the network. Extending
      discrete event simulation algorithms, our method constructs several data
      structures, and thereby reveals a variety of statistics about resource creation
      and consumption during the simulation. We use these structures to quantify the
      causal interdependence and relative importance of the reactions at arbitrary time
      intervals with respect to the network fluxes. This allows us to construct reduced
      networks that have the same flux-behavior, and compare these networks, also with
      respect to their time series. We demonstrate our approach on an extended example
      based on a published ODE model of the same network, that is, Rho GTP-binding
      proteins, and on other models from biology and ecology. CONCLUSIONS: We provide a
      fully stochastic treatment of flux analysis. As in deterministic analysis, our
      method delivers the network behavior in terms of species transformations.
      Moreover, our stochastic analysis can be applied, not only at steady state, but
      at arbitrary time intervals, and used to identify the flow of specific species
      between specific reactions. Our cases study of Rho GTP-binding proteins reveals
      the role played by the cyclic reverse fluxes in tuning the behavior of this
      network.

PMID- 24314154
TI  - Ocular blood flow decreases during passive heat stress in resting humans.
AB  - BACKGROUND: Heat stress induces various physiological changes and so could
      influence ocular circulation. This study examined the effect of heat stress on
      ocular blood flow. FINDINGS: Ocular blood flow, end-tidal carbon dioxide
      (P(ET)CO2) and blood pressure were measured for 12 healthy subjects wearing water
      perfused tube-lined suits under two conditions of water circulation: (1) at 35 
      degrees C (normothermia) for 30 min and (2) at 50  degrees C for 90 min (passive
      heat stress). The blood-flow velocities in the superior temporal retinal
      arteriole (STRA), superior nasal retinal arteriole (SNRA), and the retinal and
      choroidal vessels (RCV) were measured using laser-speckle flowgraphy. Blood flow
      in the STRA and SNRA was calculated from the integral of a cross-sectional map of
      blood velocity. PETCO2 was clamped at the normothermia level by adding 5% CO2 to
      the inspired gas. Passive heat stress had no effect on the subjects' blood
      pressures. The blood-flow velocity in the RCV was significantly lower after 30,
      60 and 90 min of passive heat stress than the normothermic level, with a peak
      decrease of 18 +/- 3% (mean +/- SE) at 90 min. Blood flow in the STRA and SNRA
      decreased significantly after 90 min of passive heat stress conditions, with peak
      decreases of 14 +/- 3% and 14 +/- 4%, respectively. CONCLUSION: The findings of
      this study suggest that passive heat stress decreases ocular blood flow
      irrespective of the blood pressure or arterial partial pressure of CO2.

PMID- 24314156
TI  - [Be vigilant against cross contamination of tumor cells in culture].

PMID- 24314155
TI  - Maternal postpartum morbidity in Marrakech: what women feel what doctors
      diagnose?
AB  - BACKGROUND: Information about postpartum maternal morbidity in developing
      countries is limited and often based on information obtained from hospitals. As a
      result, the reports do not usually reflect the true magnitude of obstetric
      complications and poor management at delivery. In Morocco, little is known about
      obstetric maternal morbidity. Our aim was to measure and identify the causes of
      postpartum morbidity 6 weeks after delivery and to compare women's perception of
      their health during this period to their medical diagnoses. METHODS: We did a
      cross-sectional study of all women, independent of place of delivery, in Al
      Massira district, Marrakech, from December 2010 to March 2012. All women were
      clinically examined 6 to 8 weeks postpartum for delivery-related morbidities. We
      coupled a clinical examination with a questionnaire and laboratory tests
      (hemoglobin). RESULTS: During postpartum consultation, 44% of women expressed at
      least one complaint. Complaints related to mental health were most often reported
      (10%), followed by genital infections (8%). Only 9% of women sought treatment for
      their symptoms before the postpartum visit. Women who were aged >=30 years,
      employed, belonged to highest socioeconomic class, and had obstetric
      complications during birth or delivered in a private facility or at home were
      more likely to report a complaint. Overall, 60% of women received a medical
      diagnosis related to their complaint, most of which were related to gynecological
      problems (22%), followed by laboratory-confirmed anemia (19%). Problems related
      to mental health represented only 5% of the diagnoses. The comparative analysis
      between perceived and diagnosed morbidity highlighted discrepancies between
      complaints that women expressed during their postpartum consultation and those
      they received from a physician. CONCLUSIONS: A better understanding of postpartum
      complaints is one of the de facto essential elements to ensuring quality of care
      for women. Sensitizing and training clinicians in mental health services is
      important to respond to women's needs and improve the quality of maternal care.

PMID- 24314157
TI  - [Prevention of ischemic stroke by homocysteine-lowering therapy: lack of
      consistent evidence].

PMID- 24314158
TI  - [A comparative study of induction of remission and cost-effectiveness of enteral
      nutrition versus infliximab in moderate-to-severe Crohn's disease].
AB  - OBJECTIVE: To compare the induction of remission and cost-effectiveness of
      enteral nutrition (EN) and infliximab (IFX) in moderate-to-severe active Crohn's
      disease(CD). METHODS: Moderate-to-severe active CD patients were divided into IFX
      group and EN group. Remission rate, time to remission and treatment cost were
      compared between the two groups. Clinical remission was defined as Crohn's
      disease activity index (CDAI) < 150. The quality of life was evaluated by
      inflammatory bowel disease questionnaire of quality of life (IBDQ). RESULTS: A
      total of 100 patients were analyzed, including 48 patients in IFX group and 52
      patients in EN group. IFX group had higher remission rate [87.5% (42/48) vs 67.3%
      (35/52) , P = 0.017] and shorter time to remission [(11.00 +/- 8.35) days vs
      (33.94 +/- 14.60) days, P < 0.001] than EN group. Treatment costs before
      remission were similar in two groups (P = 0.351) . The increase of IBDQ scores
      before and after treatment in IFX group was much higher than that of EN group
      (42.74 +/- 27.50 vs 7.57 +/- 22.77, P < 0.001) . Similarly, patients in EN group
      had greater increase of body mass index (BMI) than that of IFX group [(1.32 +/-
      0.29)kg/m(2) vs (0.51 +/- 0.07) kg/m(2), P < 0.001]. For patients with CDAI <
      280, remission rate was not significantly different [85.7% (24/28) vs 81.8%
      (18/22) , P = 0.718] between the two groups, while treatment cost in EN group was
      less than that of IFX group [(16.1 +/- 5.9)*10(3) RMB vs (22.9 +/- 11.9)*10(3)
      RMB, P = 0.021]. CONCLUSIONS: For patients with severe CD (CDAI >= 280), IFX has
      higher remission rate, shorter time to remission and comparable treatment cost
      than EN. But for patients with CDAI < 280, EN group has comparable remission rate
      to IFX group with lower cost.

PMID- 24314159
TI  - [An analysis of adverse drug reactions of thalidomide in treatment of immune
      related bowel diseases].
AB  - OBJECTIVE: To investigate the safety of thalidomide in the treatment of immune
      related bowel diseases for providing clinical reference. METHODS: Thirty-five
      patients with immune-related bowel diseases (31 Crohn's disease, 2 ulcerative
      colitis and 2 Behcet's disease) treated with thalidomide were enrolled in this
      study. The incidence, type, severity, duration of thalidomide related adverse
      drug reaction (ADR) and the dose-effect relationship of neurotoxicity were
      analyzed. RESULTS: All the patients were treated with a mean dose of thalidomide
      (109.29 +/- 30.37) mg/d for (18.8 +/- 12.4) months, and 33 occurred ADR. The
      three most frequent ADR were numbness [51.4% (18/35) ], somnolence [48.6% (17/35)
      ] and dermatitis [37.1% (13/35) ]. The median time to development of these three
      ADR were 6.50, 0.25, and 1.00 months, respectively. Severe ADR leading to
      withdrawal accounted for 20.0% (7/35), including reasons of peripheral neuritis
      (3/7), dermatitis (2/7) and myelosuppression (2/7). The incidence of peripheral
      neuritis was not significantly related to the maximal and initial dose of
      thalidomide (P > 0.05). CONCLUSIONS: Although the incidence of ADR was relatively
      high during the treatment of thalidomide, most of them were mild and well
      tolerated. Thalidomide can be safely used in patients with immune-related bowel
      diseases under close monitoring.

PMID- 24314160
TI  - [The efficacy and safety of recombinant human granulocyte colony stimulating
      factor primed donor peripheral cell harvest in treatment of poor graft function
      after allogeneic stem cell transplantation].
AB  - OBJECTIVE: To assess the efficacy and safety of recombinant human granulocyte
      colony stimulating factor (rhG-CSF) primed donor peripheral blood stem cell
      (PBSC) on the treatment of poor graft function (PGF) after allogeneic stem cell
      transplantation(allo-HSCT). METHODS: The patients diagnosed as PGF after allo
      HSCT and transfused with rhG-CSF primed PBSC from January 2003 to November 2012
      were retrospectively analyzed. Hematological response was assessed at day 30
      after transfusion. Graft versus host disease (GVHD) was assessed until 6 months
      after transfusion. RESULTS: There were 28 patients including 21 men and 7 women
      with a median age of 28 (12-50) years old. Of these patients, 16 were diagnosed
      as primary PGF. The median number of transfused mononuclear cells was 2.0 (1.0
      5.8)*10(8)/kg. Totally 42.9% (12/28) patients achieved good response. Eight
      patients (28.6%) developed GVHD. Sixteen patients (57.1%) survived. Age ( <= />28
      years), gender, donor type (matched sibling/mismatched related), additional
      conditioning regimen prior to transfusion, time of neutrophil engraftment ( <=
      />18 days) time of transfusion ( <= />100 days after allo-HSCT) and number of
      mononuclear cells ( <= />2.0*10(8)/kg) did not impact hematological response.
      However, response rate of primary PGF(4/16) was significantly lower than that of
      secondary PGF (8/12) (P = 0.022). CONCLUSION: Transfusion of PBSC mobilized by
      rhG-CSF could be considered as an option to treat secondary PGF after allogeneic
      stem cell transplantation.

PMID- 24314161
TI  - [The incidence of heparin-induced thrombocytopenia and positivity of antibody in
      patients treated with heparin preparations].
AB  - OBJECTIVES: To investigate the incidence of the heparin-induced thrombocytopenia
      (HIT) and positivity of anti-heparin/platelet factor 4 complex antibody (HIT
      antibody) in inpatients treated with heparin preparations. METHODS: A total of
      197 consecutive patients, including 120 men and 77 women, who were treated with
      unfractioned heparin (UFH) or low molecular weight heparin (LMWH), were enrolled
      in this study. HIT-antibody was detected by enzyme-linked immunosorbent assay
      (ELISA). All patients were classified into subgroups based on "4Ts" (Pretest
      Clinical Scoring System) and types of underlying disorders. The incidence of HIT
      and positivity of HIT-antibody among different groups were analyzed. RESULTS: The
      overall incidence of HIT was 3.0% (6/197), and the positivity of HIT antibody was
      12.2% (24/197). The positivity of HIT-antibody was 10.1% (18/178), 7.7% (1/13)
      and 83.3% (5/6) in low, moderate and high HIT probability group respectively.
      There were significant differences of HIT positivity and mean level of HIT
      antibody between the high HIT probability group and the low or moderate HIT
      probability group (P = 0.000). Both the incidence of HIT and positivity of HIT
      antibody were higher in surgical patients than in medical patients (5.8% vs 0.9%,
      P = 0.047 and 19.8% vs 6.3%, P = 0.004). CONCLUSIONS: The incidence of HIT and
      positivity of HIT-antibody were 3.0% and 12.2% respectively, both of which were
      related with the types of disorders. Detection of HIT-antibody has a better
      applicable value in patients with high HIT probability.

PMID- 24314162
TI  - [The clinical characteristics of 10 cases of adrenocorticotropic hormone-
      independent macronodular adrenal hyperplasia].
AB  - OBJECTIVE: To evaluate the clinical characteristics of patients with
      adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH).
      METHODS: A total of 10 AIMAH cases were enrolled in this retrospective study. The
      clinical and laboratory findings of all patients were collected and analyzed.
      RESULTS: All patients manifested some clinical features and biochemical evidence
      of Cushing's syndrome. The plasma adrenocorticotropic hormone (ACTH) level was
      undetectable in all the patients and their serum cortisol secretion rhythm was
      abnormal. Low and high-dose dexamethasone suppression tests failed to suppress
      the cortisol secretion. The bilateral macronodular adrenal enlargement was shown
      by CT/magnetic resonance imaging. The supine-upright posture test was positive in
      four patients. Three patients were performed bilateral adrenalectomy, five were
      unilateral adrenalectomy and the remaining two patients were taken propranolol.
      All the patients had followed up for 10 to 89 months. Contralateral adrenalectomy
      was performed in two patients with recurrent symptoms after unilateral
      adrenalectomy and two patients given propranolol were underwent bilateral
      adrenalectomy when their symptoms had not been improved or recurred. CONCLUSION:
      AIMAH is a relatively rare subtype of Cushing's syndrome with unique clinical and
      laboratory findings. Propranolol is a good choice if the supine-upright posture
      test is positive. Unilateral adrenalectomy appears to be an effective and safe
      alternative treatment for AIMAH. Bilateral adrenalectomy could be performed if
      the symptoms have not been improved or recurred after unilateral adrenalectomy.

PMID- 24314163
TI  - [A comparative study of the effects of needle free (INJEX30) versus insulin pen
      injection on insulin absorption in diabetic patients].
AB  - OBJECTIVE: To evaluate the effect of the needle free injection system (INJEX30)
      and insulin pen on insulin absorption and glycemic control in diabetic patients.
      METHODS: A total of 30 diabetic patients on insulin therapy without obvious
      complications were enrolled in the study with average BMI of 25.24 kg/m(2). A
      comparison study was carried out in those subjects with the INJEX30 and insulin
      pen at 1(st) day and 5(th) day. After an overnight fasting of 8-10 h, a standard
      mixed meal (50 g bread, 50 g egg and 250 ml milk) was given to each patient.
      Blood samples at 0, 20, 40, 60 min of the standard mixed meal were collected to
      test plasma glucose, serum insulin and C peptide. RESULTS: No difference was
      shown in fasting plasma glucose, serum insulin and C peptide between the patients
      with the two injection methods. The area under the curve (AUC) of plasma glucose
      and serum C peptide was significantly lower after the INJEX30 injection than that
      after insulin pen injection [plasma glucose AUC (542 +/- 172)min.mmol.L(-1) vs
      (601 +/- 199) min.mmol.L(-1), P < 0.01; C peptide AUC (70 +/- 53) min.ug. L(-1)
      vs (80 +/- 58) min.ug.L(-1), P < 0.01]. The AUC of serum insulin was
      significantly higher after the INJEX30 injection than that after insulin pen
      injection [serum insulin AUC (5621 +/- 3790) min.mIU.L(-1) vs (4285 +/- 3376)
      min.mIU. L(-1), P < 0.01]. No difference was found in the AUC of serum insulin
      between the two injection methods in the patients with BMI below 25.24 kg/m(2),
      while the AUC of serum insulin was significantly higher after the INJEX30
      injection than the insulin pen injection in the patients with BMI above 25.24
      kg/m(2) [serum insulin AUC (6453 +/- 4099) min.mIU. L(-1) vs (4879 +/- 3701)
      min.mIU.L(-1), P < 0.01]. CONCLUSION: The INJEX30 improves the serum insulin
      level which may lead to a beneficial effect on the glycemic control. Such effect
      is more obvious in the overweight patients.

PMID- 24314164
TI  - [The clinical characteristics of primary Sjogren syndrome with neuromyelitis
      optica].
AB  - OBJECTIVE: To investigate the clinical features of neuromyelitis optica (NMO) and
      NMO spectrum disorders (NMOSD) with primary Sjogren's syndrome (pSS). METHODS:
      Eleven inpatients diagnosed as NMO secondary to pSS in Peking Union Medical
      College Hospital were retrospectively analyzed. RESULTS: Eleven patients of pSS
      with NMO were enrolled in this study, including 10 females and 1 male. The mean
      age was (35 +/- 15) years old. The course of disease ranged from one month to 16
      years, with a median of 10 months. The interval between optic nerve and spinal
      cord involvement was 3 months to 2 years.Eight patients had NMOSD as initial
      presentations of pSS. Eight patients had history of optic neuropathy. The most
      frequently involved spinal segment was cervical cord (10 cases) shown by magnetic
      resonance.Serum NMO-IgG antibodies were tested in 7 patients and 6 of them were
      positive. CONCLUSION: NMOSD may present as an important and initial clinical
      manifestation of pSS, which suggesting the involvement of central nervous system.
      Autoimmune antibodies, NMO-IgG and imaging were supposed to be done for further
      evaluation of prognosis and therapy regimens.

PMID- 24314165
TI  - [The effects of aranidipine on ambulatory blood pressures in patients with mild
      to moderate essential hypertension].
AB  - OBJECTIVE: To evaluate the effect of aranidipine enteric-coated capsules on 24 h
      blood pressure and blood pressure variability (BPV) in patients with mild to
      moderate essential hypertension. METHODS: This was an open clinical trial with 2
      weeks of placebo run-in period. A total of 74 patients with blood pressure (140
      180/95-110 mm Hg (1 mm Hg = 0.133 kPa) were treated by aranidipine (5 mg/d) for 4
      weeks.If clinical sitting blood pressure < 140/90 mm Hg at 4th week, aranidipine
      at 5 mg/d would be continued for another 8 weeks.If not, the dosage would be
      increased to 10 mg/d.If blood pressure <140/90 mm Hg at 8th week, aranidipine at
      5 mg/d or 10 mg/d would be given constantly.If not, the dosage would be increased
      to 20 mg/d and given for another 4 weeks. All patients performed 24 h ambulatory
      blood pressure monitoring (ABPM) before and after the treatment with BPV
      evaluated by the average 24 h per unit time blood pressure standard deviation and
      morning blood pressure surge (MBPS). RESULTS: (1) After 12 weeks' treatment with
      aranidipine, the mean 24 h blood pressure was reduced significantly compared with
      the baseline [(14 +/- 13)/(11 +/- 9) mm Hg, both P < 0.05] with trough/peak (T/P)
      ratio of SBP and DBP in responders of 75.31% and 78.15%, respectively.(2) After
      12 weeks' treatment, standard deviations of 24 h, daytime SBP/DBP and nighttime
      SBP/DBP were reduced significantly[(25 +/- 3)/(14 +/- 4) mm Hg vs (11 +/- 3)/(8
      +/- 2) mm Hg, (24 +/- 5)/(14 +/- 4) mm Hg vs (11 +/- 3)/(8 +/- 2) mm Hg, (10 +/-
      3)/(8 +/- 4) mm Hg vs (8 +/- 3)/(6 +/- 3) mm Hg], respectively with all P <
      0.05.Significant decrease was shown in MBPS compared to the baseline [(27 +/- 11)
      mm Hg vs (19 +/- 9) mm Hg, P < 0.05]. (3) The incidence of adverse events was
      13.4%, including mild dizziness, flushing and palpitation. CONCLUSION:
      Administration of aranidipine enteric-coated capsules can control 24 h blood
      pressure effectively and reduce BPV significantly in patients with mild to
      moderate essential hypertension with good safety profile.

PMID- 24314166
TI  - [The clinical features of gastrointestinal bleeding complicating aortic
      stenosis].
AB  - OBJECTIVE: To deepen the understanding about Heyde's syndrome by investigating
      the clinical characteristics and prognosis of the patients with aortic valve
      stenosis complicating with gastrointestinal bleeding. METHODS: Patients with
      aortic valve stenosis and gastrointestinal bleeding coincidently admitted to our
      hospital from 2001 to 2011 were retrieved and analyzed. RESULTS: In all the 443
      157 in-patients, 474 patients were diagnosed with aortic valve stenosis (0.11%,
      474/443 157) and 14 patients (9 males and 5 females, aged 53-87 years old) with
      gastrointestinal bleeding coincidently(2.95%, 14/474). Among the 14 patients, 3
      were moderate aortic valve stenosis, 11 severe aortic valve stenosis. The aortic
      valve peak flow velocity was 324-709 (480.54 +/- 188.25) cm/s and the mean aortic
      valve pressure gradient was 21.04-91.56 (56.93 +/- 29.90) mm Hg(1 mm Hg = 0.133
      kPa).Heavy gastrointestinal bleeding was manifested in all the 14 patients with 1
      of haematemesis and 13 of hematochezia.Hemoglobin (Hb) and red blood cell (RBC)
      count were significantly lower than the normal range [(69 +/- 28) g/L and (2.71
      +/- 2.04)*10(12)/L, P < 0.05]. Their mean corpuscular volume(MCV), mean
      corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC),
      platelet(PLT) count, prothrombin time (PT) and international normalized ratio
      (INR) were in normal range [(90.21 +/- 2.94) fl, (29.39 +/- 1.99) pg, (327.57 +/-
      14.82) g/L, (185.13 +/- 22.55)*10(9)/L, (11.4 +/- 1.04) s and 1.22 +/- 0.44,
      respectively]. Among all the 14 patients, 13 were over 65 years old and they all
      accepted gastrointestinal imaging (13/14).Vascular malformation of intestine was
      found in 6 patients with 4 lesions located in descending colon and 2 located in
      sigmoid colon.Hemorrhage foci were found in 2 patients with one of colon cancer,
      and another of duodenal ulcer, while no definite hemorrhage foci were found in
      the other 11 patients. A total of 6 patients with severe aortic valve stenosis
      underwent aortic valve replacement (AVR) successfully (6/11) and no recurrent
      gastrointestinal bleeding was ever found. Conservative treatment was performed in
      the other 5 patients with severe aortic valve stenosis (5/11) and resulted in
      sudden death in 2 patients (2/5). CONCLUSIONS: Prompt echocardiography and
      gastrointestinal endoscopy should be performed in the elderly patients with
      obscure gastrointestinal bleeding to facilitate the early diagnosis and treatment
      of Heyde's syndrome. AVR is a fundamental procedure to improve the prognosis of
      Heyde's syndrome.

PMID- 24314167
TI  - miR-17 regulates the proliferation and differentiation of the neural precursor
      cells during mouse corticogenesis.
AB  - MicroRNAs (miRNAs) are endogenously expressed small, non-coding nucleotides that
      repress gene expression at the post-transcriptional level. In mammals, the
      developing brain contains a large, diverse group of miRNAs, which suggests that
      they play crucial roles in neural development. In the present study, we analyzed
      the miRNA expression patterns in the mouse cortex at various developmental
      stages. We found that miR-17 family miRNAs were highly expressed in the cortex
      during early developmental stages, and that their expression levels gradually
      decreased as the cortex developed. Further investigation revealed that the change
      in miR-17-5p expression occurred in the ventricular zone/sub-ventricular zone. In
      addition to promoting cell proliferation, miR-17-5p also influences the
      differentiation fate of neural precursor cells exposed to bone morphogenetic
      protein 2. Moreover, we show that these effects of miR-17-5p were mainly the
      result of regulating the bone morphogenetic protein signaling pathway by
      repressing expression of the bone morphogenetic protein type II receptor. Taken
      together, these findings suggest that miR-17 family members play a pivotal role
      in regulating cell activity during early development of the mouse cortex.

PMID- 24314168
TI  - Open questions: some unresolved issues in biodiversity.

PMID- 24314169
TI  - Kinotypes: stable species- and individual-specific profiles of cellular kinase
      activity.
AB  - BACKGROUND: Recently, questions have been raised regarding the ability of animal
      models to recapitulate human disease at the molecular level. It has also been
      demonstrated that cellular kinases, individually or as a collective unit (the
      kinome), play critical roles in regulating complex biology. Despite the intimate
      relationship between kinases and health, little is known about the variability,
      consistency and stability of kinome profiles across species and individuals.
      RESULTS: As a preliminary investigation of the existence of species- and
      individual-specific kinotypes (kinome signatures), peptide arrays were employed
      for the analysis of peripheral blood mononuclear cells collected weekly from
      human and porcine subjects (n = 6) over a one month period. The data revealed
      strong evidence for species-specific signalling profiles. Both humans and pigs
      also exhibited evidence for individual-specific kinome profiles that were
      independent of natural changes in blood cell populations. CONCLUSIONS: Species
      specific kinotypes could have applications in disease research by facilitating
      the selection of appropriate animal models or by revealing a baseline kinomic
      signature to which treatment-induced profiles could be compared. Similarly,
      individual-specific kinotypes could have implications in personalized medicine,
      where the identification of molecular patterns or signatures within the kinome
      may depend on both the levels of kinome diversity and temporal stability across
      individuals.

PMID- 24314170
TI  - Spatial autocorrelation in uptake of antenatal care and relationship to
      individual, household and village-level factors: results from a community-based
      survey of pregnant women in six districts in western Kenya.
AB  - BACKGROUND: The majority of maternal deaths, stillbirths, and neonatal deaths are
      concentrated in a few countries, many of which have weak health systems, poor
      access to health services, and low coverage of key health interventions. Early
      and consistent antenatal care (ANC) attendance could significantly reduce
      maternal and neonatal morbidity and mortality. Despite this, most Kenyan mothers
      initiate ANC care late in pregnancy and attend fewer than the recommended visits.
      METHODS: We used survey data from 6,200 pregnant women across six districts in
      western Kenya to understand demand-side factors related to use of ANC. Bayesian
      multi-level models were developed to explore the relative importance of
      individual, household and village-level factors in relation to ANC use. RESULTS:
      There is significant spatial autocorrelation of ANC attendance in three of the
      six districts and considerable heterogeneity in factors related to ANC use
      between districts. Working outside the home limited ANC attendance. Maternal age,
      the number of small children in the household, and ownership of livestock were
      important in some districts, but not all. Village proportions of pregnancy in
      women of child-bearing age was significantly correlated to ANC use in three of
      the six districts. Geographic distance to health facilities and the type of
      nearest facility was not correlated with ANC use. After incorporating individual,
      household and village-level covariates, no residual spatial autocorrelation
      remained in the outcome. CONCLUSIONS: ANC attendance was consistently low across
      all the districts, but factors related to poor attendance varied. This
      heterogeneity is expected for an outcome that is highly influenced by socio
      cultural values and local context. Interventions to improve use of ANC must be
      tailored to local context and should include explicit approaches to reach women
      who work outside the home.

PMID- 24314171
TI  - Royal Australasia of Surgeons Guest Lecture. Necrotizing enterocolitis:
      prevention, treatment, and outcome.
AB  - Necrotizing enterocolitis (NEC) remains a very serious disease, particularly in
      premature infants. This review describes various aspects of the diagnosis and
      treatment of the disease. The pathogenesis of NEC is not completely understood,
      and risk factors include formula enteral feeding and bacterial involvement.
      Prevention of the disease is desirable, and the most robust evidence is linked to
      the protective effet of human milk and probiotics. The medical and surgical
      management has not changed significantly in the last 20 years. Insertions of
      peimary peritoneal drainage in comparison with laparotomy remain controversial,
      and this uncertainty stimulated the development of two randomized controlled
      trials. Neither definitely demonstrated an advantage of either periotneal
      drainage or laparotomy over the other. The advantage offered by a stoma compared
      to primary intestinal anastomosis is currently investigated in a multicenter
      randomized controlled trial (STAT Trial). The mortality of the disease remains
      high, and new therapeutic interventions are needed. Novel forms of treatment that
      can improve the outcome of this disease are currently under investigation. These
      include whole-body moderately controlled hypothermia and administration of
      amniotic fluid stem cells.

PMID- 24314172
TI  - Factors influencing jaundice-free survival with the native liver in post
      portoenterostomy biliary atresia patients: results from a single institution.
AB  - PURPOSE: We reviewed post-portoenterostomy (PE) biliary atresia (BA) patients who
      became "jaundice-free" (JF; total bilirubin (T-bil) <=1.2 mg/dL) to determine
      factors associated with survival with the native liver (SNL). METHODS: We
      reviewed 76 BA patients treated by PE at our institute between 1989, when liver
      transplantation (LTx) became available in Japan, and 2012, prospectively. Of
      these, 60 who became JF and remained JF were divided into two groups, SNL (n=44)
      and LTx (n=16). Age and weight at PE, pre- and post-PE T-bil, AST, gamma-GT, time
      taken to become JF, corticosteroid requirements, incidence of cholangitis, and
      micro-bile duct size were compared between the two groups. RESULTS: The SNL
      patients became JF significantly earlier: 58 vs. 115 days (p<.05). Corticosteroid
      requirement, cholangitis, and postoperative AST/gamma-GT were significantly lower
      in the SNL patients (p<.05). SNL was significantly higher if patients became JF
      <=60 days post-PE (p<.01). LTx was performed from 0.5 to 11 years post-PE
      (mean=3.4). All patients who had cholangitis within 3 months of PE eventually
      required LTx (p<.05). CONCLUSIONS: Becoming JF <=60 days post-PE would appear to
      be a factor associated with SNL, while cholangitis within 3 months of PE would
      appear to be associated with LTx. Elevation of AST and gamma-GT would also appear
      to be early indicators of risk for LTx during follow-up of JF patients after
      successful PE.

PMID- 24314173
TI  - The most reliable early predictors of outcome in patients with biliary atresia
      after Kasai's operation.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to determine reliable
      predictors of outcome of biliary atresia (BA) after Kasai's operation. PATIENTS
      AND METHODS: Fifty-four BA cases that underwent Kasai's operation at our
      institution over two decades were reviewed. The cases were divided into two
      groups: Group I: cases that required liver transplantation or died (n=30) and
      Group II: cases alive with the native liver. Serum levels of total bilirubin
      (TB), direct bilirubin (DB), aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were measured
      sequentially after surgery. For cut-off determination, receiver operating
      characteristic (ROC) analysis was employed. RESULTS: Serum TB, DB, AST, and ALT
      in Group I were significantly higher than those in Group II at 1, 2, and 3 months
      after surgery (p<.05). The most reliable cut-offs determined by ROC analysis were
      DB of 0.7 mg/dl at 2 months (sensitivity; 93%, specificity; 75%) and AST of 94
      IU/L at 2 months (sensitivity; 87%, specificity; 71%). The 54 cases were re
      divided into three groups according to the cut-off values: group G (good) with DB
      and AST<cut-offs (n=16; Group I:II=1:15), group M (moderate) with DB or AST>cut
      offs (n=9; Group I:II=4:5), and group P (poor) with DB and AST >= cut-offs (n=29;
      Group I:II=25:4). The 15-year survival rate in groups G, M, and P was 94%, 44%,
      and 22%, respectively (p<.001). CONCLUSION: The combination of serum DB and AST
      at 2 months after Kasai's operation is a reliable predictor of long-term BA
      outcome.

PMID- 24314174
TI  - Preoperative imaging does not predict intrahepatic involvement in choledochal
      cysts.
AB  - INTRODUCTION: Choledochal cyst (CDC) is a congenital malformation of the bile
      ducts, which can include the intrahepatic or extrahepatic bile ducts. We
      hypothesize that preoperative intrahepatic ductal dilation is not predictive of
      postoperative intrahepatic involvement. METHODS: We retrospectively reviewed all
      cases of CDC in children diagnosed at a single institution between 1991 and 2013.
      RESULTS: Sixty-two patients were diagnosed with CDC during the study period with
      a median follow-up time of 2.25 (range 0-19.5) years. Forty-two patients (68%)
      were diagnosed with type I disease preoperatively, and 15 patients (24%) were
      diagnosed with type IV-A disease. The most common presenting symptoms included
      pain (34%), jaundice (28%), and pancreatitis (25%). There were no deaths or
      malignancies and only one postoperative stricture. Forty-two patients (68%) had
      intrahepatic ductal dilation preoperatively. Only four patients (9%) had
      intrahepatic ductal dilation following resection (P<0.0001). In one patient, this
      dilation resolved following stricture revision. Of the four patients with
      postoperative dilation, two were diagnosed with type I disease, and the other two
      were diagnosed with type IV-A disease preoperatively. CONCLUSION: Preoperative
      intrahepatic ductal dilation is not predictive of postoperative intrahepatic
      ductal involvement in children with CDC. The preoperative distinction between
      type I and IV disease is not helpful in treating these patients.

PMID- 24314176
TI  - Covered cloacal exstrophy--a poorly recognized condition: hints for a correct
      diagnosis.
AB  - INTRODUCTION: Covered cloacal exstrophy requires a high index of suspicion for
      its diagnosis. Low implantation of the umbilical cord, separated pubic bones, and
      anorectal malformation are the most common signs. METHODS: Thirty-one patients
      with this defect were retrospectively analyzed. RESULTS: Besides the anorectal
      malformation, the patients had important unique anatomic findings, including a
      colon shorter than 20 cm (17 patients) and absent bladderneck (27 patients).
      Twenty-four patients underwent a colonic pullthrough; of those, only 5 of them
      have voluntary bowel movements. Twelve patients underwent a urinary
      reconstruction. Eleven of them are dry with catheterization, and one leaks in
      between catheterization. Two patients are urinary continent. CONCLUSIONS: Covered
      exstrophy is a serious condition. Externally, the patients may look like having a
      rather simple malformation. However, the intra-abdominal findings are similar to
      those seen in cloacal exstrophy. An early correct diagnosis is important to plan
      a reconstructive strategy and to adjust the parent's expectations concerning
      bowel and urinary function. In addition to the traditional prognostic factors for
      bowel and urinary control (sacral ratio, tethered cord, and level of the rectum)
      these patients have other anatomic defects (absent bladderneck and short colon)
      that negatively affect the functional prognosis.

PMID- 24314175
TI  - Multicenter retrospective comparative study of laparoscopically assisted and
      conventional anorectoplasty for male infants with rectoprostatic urethral
      fistula.
AB  - BACKGROUND: Laparoscopically assisted anorectoplasty (LAARP) was expected to
      achieve better fecal continence than conventional procedures. However, the issue
      of which approach is better remains controversial. We compared outcomes between
      the conventional procedure and LAARP in male infants with rectoprostatic urethral
      fistula. METHODS: Institutes belonging to the Japanese Study Group of Anorectal
      Anomalies (JSGA) were invited to participate. Subjects were male infants with
      rectoprostatic urethral fistula treated by the conventional approach
      (abdominoperineal pull-through and PSARP) or LAARP between 2000 and 2006. Medical
      charts and operative records were reviewed retrospectively. RESULTS: Eighty-one
      patients (conventional: 36, LAARP: 45) were enrolled from 15 centers. In both
      groups, the mean Kelly score was 5. The total score of the scoring system was
      newly developed by the Japanese Study Group of Anorectal Anomalies. Follow-up
      Project (5-15 points) was 10.7 and 12.1 in the conventional group and the LAARP
      group, respectively (p=0.07). The incidence of failed rectoanal anastomosis,
      mucosal prolapse, and anal stenosis was comparable in both groups. Posterior
      urethral diverticula were detected on cystourethrograms in 7% and 11% (p=1.0) and
      on MRI in 0% and 34% (p=0.02) of the conventional and the LAARP groups,
      respectively. Overall, 94% of diverticula were asymptomatic. CONCLUSIONS: Fecal
      continence and complication rates after LAARP were comparable to those observed
      after the conventional method. Posterior urethral diverticula were detected more
      frequently after LAARP.

PMID- 24314177
TI  - No TAP63 promoter mutation is detected in bladder exstrophy-epispadias complex
      patients.
AB  - BACKGROUND/PURPOSE: Bladder exstrophy-epispadias complex (BEEC) is thought to
      have a genetic component in its pathogenesis. Previously we found that p63(-/-)
      mice show increased ventral apoptosis and develop a BEEC phenotype. Down
      regulation of the anti-apoptotic DeltaNP63 and an up-regulation of pro-apoptotic
      TAP63 isoforms have been demonstrated in BEEC patient bladder tissues. We have
      previously shown that insertion/deletion polymorphisms of the DeltaNp63 promoter
      are associated with an increased risk of BEEC. In this study, we specifically
      examined the TAP63 promoter to see if any sequence changes might lead to up
      regulation of TAP63 and exaggerated apoptosis in BEEC patients. METHODS: i)
      Bioinformatic analysis of the TAP63 promoter was performed to identify putative
      regulatory regions. ii) High-resolution Melt and Sanger sequencing was used to
      screen targeted regions in 112 BEEC patient DNA samples for potential sequence
      variants. iii) Sequence variation was analysed for significance against normal
      population frequency data. RESULTS: i) We identified multiple epigenetic markers
      of transcriptional regulation within highly conserved areas of the TAP63 promoter
      sequence. ii) Of the 112 buccal swab DNA samples, adequate and successful
      screening ranged between 48 and 67 for each region. iii) No novel sequence
      variation or mutation was uncovered. iv) Two known SNPs were identified. However,
      allele frequency analysis was not statistically significant. CONCLUSION: Our data
      do not associate genetic variation within the TAP63 promoter region with an
      increased risk of BEEC. Our data so far suggests that only DeltaNP63 promoter
      aberration is involved in BEEC pathogenesis.

PMID- 24314178
TI  - The increasing incidence of adolescent bariatric surgery.
AB  - BACKGROUND: Morbid obesity continues to be a significant problem within the
      United States, as overweight/obesity rates are nearing 33%. Bariatric surgery has
      had success in treating obesity in adults and is becoming a viable treatment
      option for obese adolescents. METHODS: We studied 1615 inpatient admissions for
      children <=20 years of age undergoing a bariatric procedure for morbid obesity in
      2009 using the Kids' Inpatient Database (KID). Patients had a principal diagnosis
      of obesity and a bariatric procedure listed as one of their first 5 procedures.
      Procedures (open gastric bypass, laparoscopic gastric bypass, sleeve gastrectomy,
      laparoscopic gastroplasty, and laparoscopic gastric band) and complications were
      defined by ICD-9 codes. RESULTS: There were 90 open gastric bypasses, 906
      laparoscopic gastric bypasses, 150 sleeve gastrectomies, 18 laparoscopic
      gastroplasties, and 445 laparoscopic gastric bandings. The length of stay for
      each procedure was 2.44, 2.20, 2.33, 1.10, and 1.02 days, respectively (P<0.001).
      The complication rates were 3.3%, 3.5%, 0.7%, 0.0%, 0.2%, respectively (P=0.004).
      CONCLUSIONS: Bariatric surgery is an increasingly utilized option for the
      treatment of morbid obesity among adolescents. The procedures can be performed
      safely as evidenced by low complication rates. Additional long-term follow-up is
      necessary.

PMID- 24314179
TI  - Standardized reporting for congenital diaphragmatic hernia--an international
      consensus.
AB  - BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) remains a significant
      cause of neonatal death. A wide spectrum of disease severity and treatment
      strategies makes comparisons challenging. The objective of this study was to
      create a standardized reporting system for CDH. METHODS: Data were prospectively
      collected on all live born infants with CDH from 51 centers in 9 countries.
      Patients who underwent surgical correction had the diaphragmatic defect size
      graded (A-D) using a standardized system. Other data known to affect outcome were
      combined to create a usable staging system. The primary outcome was death or
      hospital discharge. RESULTS: A total of 1,975 infants were evaluated. A total of
      326 infants were not repaired, and all died. Of the remaining 1,649, the defect
      was scored in 1,638 patients. A small defect (A) had a high survival, while a
      large defect was much worse. Cardiac defects significantly worsened outcome. We
      grouped patients into 6 categories based on defect size with an isolated A defect
      as stage I. A major cardiac anomaly (+) placed the patient in the next higher
      stage. Applying this, patient survival is 99% for stage I, 96% stage II, 78%
      stage III, 58% stage IV, 39% stage V, and 0% for non-repair. CONCLUSIONS: The
      size of the diaphragmatic defect and a severe cardiac anomaly are strongly
      associated with outcome. Standardizing reporting is imperative in determining
      optimal outcomes and effective therapies for CDH and could serve as a benchmark
      for prospective trials.

PMID- 24314180
TI  - Effects of rapamycin on granulation formation in response to centrally doubled
      coiled stents as a tracheal substitute.
AB  - INTRODUCTION: In experiments involving tracheal wall defects in rabbits, metallic
      coil stents inevitably induce granulation formation in the defects. We examined
      the involvement of the mammalian target of rapamycin (mTOR) signaling pathway in
      granulation formation and examined the effects of rapamycin. METHODS: The
      anterior half of the tracheal wall was removed for a longitudinal length of six
      tracheal rings. Metallic coils were placed into the tracheal lumen through a wall
      defect. The rabbits were sacrificed two months after undergoing an endoscopic
      examination, and the granulation tissue in the tracheal defects was removed for a
      Western blot analysis and immunohistochemical analysis. Rapamycin (0.5 mg kg(-1)
      day(-1)) was administered three times per week intramuscularly. The data were
      expressed as the relative expression versus the expression of actin. RESULTS: The
      level of mTOR phosphorylation in the resected trachea was 0.72+/-0.45, and it
      significantly increased in the granulation tissue to 11.6+/-5.2, with concomitant
      increases in the phosphorylation levels of p70S6K and S6RP in all five rabbits.
      Although the systemic administration of rapamycin significantly decreased the
      levels of phosphorylated mTOR to 4.0+/-2.4 in the five treated rabbits, the
      clinical outcomes were unsatisfactory. Three of the five treated rabbits
      exhibited signs of wound complications, and wet granulation tissue that caused
      respiratory symptoms was found inside and outside of the coils in four rabbits.
      CONCLUSIONS: Although rapamycin effectively reduced the mTOR activity in the
      granulation tissue, the granulation formation process seemed to be disturbed,
      most likely owing to the immunosuppressive effects of rapamycin.

PMID- 24314181
TI  - Postoperative pain management in pediatric patients undergoing minimally invasive
      repair of pectus excavatum: the role of intercostal block.
AB  - PURPOSE: There are no published data regarding value of intercostal block
      following pectus excavatum repair. Our aim was to evaluate the efficacy of
      intercostal block in children following minimally invasive repair of pectus
      excavatum (MIRPE). METHODS: Forty-five patients given patient-controlled
      analgesia (PCA) with morphine postoperatively were studied. Twenty-six patients
      were given bilateral intercostal blocks after induction of anesthesia (PCA-IB
      group), and nineteen patients were retrospective controls without regional
      blockade (PCA group). All patients were followed up 24 h postoperatively.
      RESULTS: A loading dose of morphine (0,1+/-0,49 mg/kg) before starting PCA was
      used in seventeen patients in PCA group vs. no patient in PCA-IB group.
      Cumulative used morphine doses were lower up to 12 h after surgery in PCA-IB
      group (0,29+/-0,08 MUg/kg) than in the PCA group (0,46+/-0,18 MUg/kg), p<0,01.
      There were no differences in pain scores, oxygen saturation values, sedation
      scores, and the incidence of pulmonary adverse events between the two groups.
      There was a tendency towards less morphine-related adverse effects in PCA-IB
      group compared to PCA group (p<0,05). No complications related to the intercostal
      blocks were observed. CONCLUSION: Bilateral intercostal blocks following MIRPE
      are safe and easy to perform and can diminish postoperative opioid requirement.
      Double-blind randomized study is required to confirm the potential to diminish
      opioid related side effects.

PMID- 24314182
TI  - Hoxa-11 maintains cell proliferation in the mouse gubernaculum to facilitate
      testicular descent.
AB  - INTRODUCTION: The gubernaculum is a structure vital for guiding testicular
      descent. The Homeobox gene, Hoxa-11, is involved in patterning embryonic
      structures and is necessary for gubernacular development, as Hoxa-11 knock-out
      mice exhibit abnormal gubernacula and undescended testes. We aimed to elucidate
      how testicular descent fails by examining cell proliferation and androgen
      receptor (AR) expression in Hoxa-11 KO mice gubernacula. METHODS: Postnatal day 2
      wild type (n=6) and Hoxa-11 KO mice (n=6), were prepared for immunohistochemistry
      and confocal microscopy using antibodies against androgen receptor, slow skeletal
      myosin (My32), and Ki67, a marker of cell proliferation. RESULTS: The gubernacula
      of Hoxa-11 KO mice were hypocellular compared with WT. AR was present in the
      gubernaculum and abutting inguinal fat pad in both WT and Hoxa-11 KO with no
      difference in expression. Slow skeletal myosin was present in a clear 'swirl' in
      the growth centre of WT animals which was absent in the Hoxa-11 KO mice. Ki67,
      expressed in the growth centre and cremaster muscle in WT, was greatly decreased
      in Hoxa-11 KO. CONCLUSION: Hoxa-11 may regulate fibroblast proliferation in the
      gubernaculum, as it does in human uterosacral ligaments, allowing formation of
      the 'growth centre' within the bulb and facilitating myogenesis and elongation to
      the scrotum. Polymorphisms in Hoxa-11 may contribute to the aetiology of human
      cryptorchidism.

PMID- 24314183
TI  - Follow up of prospective validation of an abbreviated bedrest protocol in the
      management of blunt spleen and liver injury in children.
AB  - OBJECTIVE: Current APSA recommendations for blunt spleen/liver injury (BSLI)
      entail bedrest equal to grade of injury plus one. We reported our experience 3
      years ago with a prospectively implemented abbreviated protocol, one concern of
      which was that more numbers would be needed to support the safety of such a
      protocol. We are now reporting the final experience with this protocol as we move
      forward with further investigation. METHODS: Following IRB approval, data were
      collected prospectively in all patients with BSLI up to 8 weeks after discharge.
      There were no exclusion criteria, and patient accrual was consecutive. Bedrest
      was restricted to one night for Grade I & II injuries and two nights for Grade >=
      III. RESULTS: Between 11/2006 and 10/2012, 249 patients were admitted with BSLI.
      Mean age and weight were 10.3+/-4.8 years and 40.1+/-19.8 kg, respectively.
      Injuries included isolated spleen in 130 (52%), liver only in 107 (43%), and both
      in 12 (5%). One splenectomy was required for a grade V injury. Transfusions were
      used in 40 patients (16%), with 28 (11%) due to the injured solid organ. Bedrest
      for solid organ injury was applicable to 199 patients (80%), for which the mean
      grade of injury was 2.7+/-1.0 and mean bedrest was 1.6+/-0.6 days, resulting in
      2.5+/-1.9 days of hospitalization. The need for bedrest was the limiting factor
      for length of stay in 155 patients (62%), for which mean grade of injury was
      2.5+/-1.0 and mean bedrest was 1.6+/-0.6 days, resulting in 1.7+/-0.8 days of
      hospitalization. There were 4 deaths, 3 from brain injury and 1 from grade V
      liver injury. There were no patients readmitted for complications of solid organ
      injury. CONCLUSIONS: These data further validate that an abbreviated protocol of
      one night of bedrest for grade I and II injuries and two nights for grade >= III
      can be safely employed, resulting in dramatic decreases in hospitalization
      compared to the current APSA recommendations.

PMID- 24314184
TI  - Pediatric appendicitis: the prevalence of systemic inflammatory response syndrome
      upon presentation and its association with clinical outcomes.
AB  - INTRODUCTION: To our knowledge, the prevalence of Systemic Inflammatory Response
      Syndrome (SIRS) in pediatric patients with appendicitis has not been previously
      investigated. Our specific aim was to determine the prevalence of SIRS at the
      time of presentation of pediatric patients with appendicitis. Additionally, we
      sought to determine if the presence of SIRS had any value in predicting their
      clinical outcomes. METHODS: This retrospective cohort study included pediatric
      patients (age <17 years) presenting to a single hospital and being diagnosed with
      appendicitis between July 1, 2011, and June 30, 2012. The primary exposure
      variable of interest was SIRS, dichotomously defined as positive or negative. The
      primary outcome of interest was the presence/development of an intraabdominal
      abscess. The secondary outcome of interest was length of hospital stay (LOS). Chi
      squared and t-tests were used to evaluate the association between presence of
      SIRS and development of abscess and LOS. RESULTS: This study consisted of 212
      patients. The definition of SIRS was met in 66 patients (31.1%). Thirty of the 66
      (45.6%) patients with SIRS had/developed an abscess versus 28 (19.2%) of those
      without SIRS (P<0.001). Patients with SIRS had a mean LOS of 4 days (+/-2.7),
      while those without SIRS stayed a mean of 2.5 days (+/-2.3) [p<0.0001]).
      Adjusting for age did not alter these associations. CONCLUSION: Our study found a
      31.1% prevalence of SIRS in pediatric patients presenting with appendicitis. Our
      results suggest these patients with SIRS have a significantly higher risk of
      having/developing an intraabdominal abscess (RR, 2.4; 95% CI: 1.6-3.6) and
      significantly longer LOS.

PMID- 24314185
TI  - Morphology of nervous lesion in the spinal cord and bladder of fetal rats with
      myelomeningocele at different gestational age.
AB  - OBJECTIVE: To analyze the development and innervation of bladder smooth muscle
      and lesions of the spinal cord in fetal rats with meningomyelocele (MMC) at
      different gestational ages and to investigate interactions between spinal cord
      lesions and bladder. METHOD: Each fetus was assigned to the MMC group or the
      normal group. Each group was further divided into three subgroups by gestational
      age: E16, E18, and E20 (embryonic days 16, 18, and 20, respectively). alpha-Actin
      and neurotubulin-beta-III were analyzed in the bladder, and GFAP and VAChT were
      analyzed in the lumbosacral spinal cord by immunohistochemistry. Photographs were
      taken to determine the integrated optical density of each sample. RESULTS:
      Neurotubulin-beta-III was significantly lower in the MMC group than in the normal
      group at all fetal ages. Abundant alpha-actin was detected in both groups at all
      fetal ages. No significant difference was found between the MMC group and the
      normal group at any fetal age. At E16 and E18, no GFAP-positive astrocyte was
      detected in the MMC group or the normal group. At E20, numerous GFAP-positive
      astrocytes were detected in the MMC group, with significant difference from the
      normal group. VAChT was detected less in the MMC group than in the normal group
      at all fetal ages with significant differences. CONCLUSION: Bladder smooth muscle
      of fetal MMC rat seems morphologically normal in development, while the
      innervation of the bladder smooth muscle is markedly decreased centrally and
      peripherally. Astrocytosis appears at a later embryonic stage, which could be a
      concern in the nerve repair of the spinal cord.

PMID- 24314186
TI  - Effect of propranolol vs prednisolone vs propranolol with prednisolone in the
      management of infantile hemangioma: a randomized controlled study.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to compare the efficacy of
      orally administered propranolol versus prednisolone versus both in the treatment
      of potentially disfiguring or functionally threatening infantile hemangiomas.
      MATERIAL AND METHODS: A prospective study of 30 patients aged 1 week-8 months was
      randomized into three equal groups. These were as follows: A, propranolol (2-3
      mg/kg/d); B, prednisolone (1-4 mg/kg/d); and C, receiving both for a minimum
      duration of 3 months. Dimensions, color, consistency, ultrasonography,
      photographic documentation based on Visual Analogue Scale (VAS) were recorded
      before and periodically after starting treatment. A minimum 75% improvement was
      considered as success with no regrowth up to 1 month of stopping treatment.
      RESULTS: Mean initial response time (days) in A (4.1+/-3.3 SD) and C (4.7+/
      3.4SD) was significantly lower than B (9.78+/-7.8SD) (p<0.047). Significant
      change in consistency was noted very early in A (24 hours) compared to B and C (8
      days). VAS results are as follows: (a) color fading--significant reduction in A
      within 48 hours compared to B and C (p=0.025), (b) flattening--more significant
      and earlier in A and C than B (p<0.05), and (c) mean reduction in size:
      significant in A and C at 3 months (p=0.005, p=0.005), 6 months (p=0.005,
      p=0.008), 12 months (p=0.005, p=0.008), and 18 months (p=0.02, p=0.04), whereas
      in B, it was seen only at 6 months (p=0.008). CONCLUSIONS: Propranolol had a
      consistent, rapid therapeutic effect compared to prednisolone. A combination of
      the two had a comparable but not higher efficacy than propranolol alone.
      Prednisolone was associated with a higher number of complications, thereby
      decreasing patient compliance.

PMID- 24314187
TI  - Antiangiogenic effect of propranolol on the growth of the neuroblastoma
      xenografts in nude mice.
AB  - BACKGROUND: Propranolol has been reported to display an antiangiogenic effect on
      infantile hemangiomas and also some adult cancers. Little is known, however,
      about whether propranolol has such effect on pediatric malignancies. METHODS:
      Nude mice bearing BE(2) C neuroblastoma xenografts were injected
      intraperitoneally with propranolol and divided into groups of PROP-2 (n=11), -5
      (n=11), and -10 (n=10) according to the treating dosages of 2, 5, and 10 mg kg(
      1) day(-1), respectively. The tumor volume and body weight were recorded every
      other day. All mice were sacrificed on day 9, and the levels of angiogenic
      factors were measured in harvested xenografts by immunohistochemistry and western
      blotting. RESULTS: The tumor volume and weight of PROP-2 (0.72+/-0.28 cm(3),
      0.59+/-0.21 g) and PROP-5 (0.81+/-0.35 cm(3), 0.61+/-0.25 g) were significantly
      decreased when compared with those of CTL (1.22+/-0.58 cm(3), 0.93+/-0.15 g;
      P<0.01). The tumor microvessel density (MVD) scores that PROP-2, -5, and -10
      groups had (49.28+/-17.53, 52.45+/-17.11, and 51.09+/-13.18 pixels per picture,
      respectively) were lower than those from the control group (65.29+/-17.33 pixels
      per picture, P<0.01). Furthermore, vascular endothelial growth factor (VEGF),
      metalloproteinase-2 (MMP-2), and metalloproteinase-9 (MMP-9) levels were
      significantly lower in the groups with propranolol treated dosage of 5 and 10 mg
      kg(-1)day(-1) than in the control group. CONCLUSIONS: Propranolol can exhibit an
      inhibitory effect on the tumor growth and angiogenic factors expression in
      neuroblastoma xenografts, which may provide some knowledge to the role of beta
      blockers in the management of NB.

PMID- 24314188
TI  - Knockdown of beta-catenin expression inhibits neuroblastoma cell growth in vitro
      and in vivo.
AB  - OBJECTIVE: The purpose of this study was to investigate the inhibitory effect of
      beta-catenin gene silencing on regulation of the biological behavior of
      neuroblastoma BE(2)C cells in vivo and in vitro. METHODS: A lentivirus, carrying
      beta-catenin siRNA, was used to stably knockdown beta-catenin expression in
      neuroblastoma BE(2)C cells for assessing tumor cell viability, colony formation,
      cell cycle distribution, apoptosis, xenograft formation, and growth in nude mice.
      RESULTS: Levels of beta-catenin expression were markedly decreased in BE(2)C
      cells. Downregulation of beta-catenin was concomitantly accompanied by reductions
      in colony formation and invasion capacity and by growth inhibition of BE(2)C
      cells in vitro. The mechanism appears to be a G0/G1 phase arrest and induction of
      apoptosis. In vivo, both tumor volume and weight of beta-catenin knockdown cells
      were obviously reduced compared to the control and parental cells. CONCLUSION:
      beta-Catenin knockdown could effectively control growth of neuroblastoma cells in
      vitro and in nude mice, suggesting that targeting beta-catenin may be useful in
      clinical control of neuroblastoma.

PMID- 24314189
TI  - Outcomes of pulmonary metastases in hepatoblastoma--is the prognosis always poor?
AB  - BACKGROUND: Hepatoblastoma is a rare tumour accounting for approximately 1% of
      all paediatric malignancies. Hepatoblastoma complicated by pulmonary metastatic
      disease continues to cause management difficulties due to a lack of robust
      evidence and treatment guidelines. METHOD: This series is the experience of a
      tertiary paediatric referral centre. Patients were prospectively enlisted, and
      their charts were retrospectively reviewed. RESULTS: Thirty-seven patients were
      treated for hepatoblastoma from 1995 to 2012 inclusive. The overall survival was
      34/37(91.9%). Eight patients had lung metastases at diagnosis (LMD) and twenty
      nine did not (NLMD). Two-year EFS was 62.5% in the LMD group and 89.3% in the
      NLMD group (p=0.078). Overall survival in the LMD and NLMD groups was 100% and
      89.7%, respectively (p=0.389). Two patients in the LMD group required multiple
      thoracic resections to achieve cure. Within the NLMD group, two patients
      developed lung metastases whilst on treatment, and both of these patients died.
      CONCLUSION: In this series, children presenting with lung metastases had a higher
      risk of relapse but excellent overall survival. However, children who developed
      pulmonary disease during treatment had a poor prognosis. We advocate aggressive
      surgical treatment of pulmonary hepatoblastoma to achieve cure.

PMID- 24314190
TI  - An augmented reality navigation system for pediatric oncologic surgery based on
      preoperative CT and MRI images.
AB  - PURPOSE: In pediatric endoscopic surgery, a limited view and lack of tactile
      sensation restrict the surgeon's abilities. Moreover, in pediatric oncology, it
      is sometimes difficult to detect and resect tumors due to the adhesion and
      degeneration of tumors treated with multimodality therapies. We developed an
      augmented reality (AR) navigation system based on preoperative CT and MRI imaging
      for use in endoscopic surgery for pediatric tumors. METHODS: The patients
      preoperatively underwent either CT or MRI with body surface markers. We used an
      optical tracking system to register the reconstructed 3D images obtained from the
      CT and MRI data and body surface markers during surgery. AR visualization was
      superimposed with the 3D images projected onto captured live images. Six patients
      underwent surgery using this system. RESULTS: The median age of the patients was
      3.5 years. Two of the six patients underwent laparoscopic surgery, two patients
      underwent thoracoscopic surgery, and two patients underwent laparotomy using this
      system. The indications for surgery were local recurrence of a Wilms tumor in one
      case, metastasis of rhabdomyosarcoma in one case, undifferentiated sarcoma in one
      case, bronchogenic cysts in two cases, and hepatoblastoma in one case. The
      average tumor size was 22.0+/-14.2 mm. Four patients were treated with
      chemotherapy, three patients were treated with radiotherapy before surgery, and
      four patients underwent reoperation. All six tumors were detected using the AR
      navigation system and successfully resected without any complications.
      CONCLUSIONS: The AR navigation system is very useful for detecting the tumor
      location during pediatric surgery, especially for endoscopic surgery.

PMID- 24314192
TI  - Esophageal atresia: gastroesophageal functional follow-up in 5-15 year old
      children.
AB  - PURPOSE: Esophageal atresia (EA) is one of the most frequent congenital
      alimentary tract anomalies with a considerable morbidity throughout childhood.
      This study evaluates the gastroesophageal problems in 5-15 year old children with
      EA and aims to identify factors predisposing to esophagitis in EA. MATERIAL AND
      METHODS: Fifty-nine patients primarily operated at Odense University Hospital,
      Denmark, during 1993-2005 were included in this follow-up study. The patients
      underwent the following examinations: Interview, upper endoscopy, endoscopic
      ultrasonography, high-resolution esophageal manometry (HREM), and pH- and
      multichannel intraluminal impedance (MII) measurements. Twenty-five patients with
      suspected gastro-esophageal reflux disease (GERD) underwent the same
      investigations and served as controls. RESULTS: Median age was 10.2 years (7.1
      13.3). Thirty-three (55.9%) presented with GERD symptoms, 41 (69.5%) with
      dysphagia, and 33 (55.9%) with respiratory symptoms. Twenty-nine (49.2%) had
      endoscopic esophagitis, and 26 (44.1%) histological esophagitis. Median reflux
      index (RI) was 8.3 (4.8-14.9). In 32 (55.2%) RI was above 7. Ten percent had
      eosinophilic inflammation. HREM showed dysmotility in the esophagus in all EA
      patients, 83.3% had no propagating swallows. No predictive factors predisposing
      the development of endoscopic esophagitis were identified. CONCLUSIONS:
      Gastroesophageal problems in children born with EA are common. Routine follow-up
      with endoscopy and pH-metry in EA patients is warranted.

PMID- 24314193
TI  - Evaluation of gastroesophageal function and mechanisms underlying
      gastroesophageal reflux in infants and adults born with esophageal atresia.
AB  - PURPOSE: To evaluate the mechanisms underlying gastroesophageal reflux (GER)
      following esophageal atresia (EA) repair and gastroesophageal function in infants
      and adults born with EA. METHODS: Ten consecutive infants born with EA as well as
      10 randomly selected adult EA patients were studied during their first
      postoperative follow-up visit and a purposely planned visit, respectively. A
      (13)C-octanoate breath test and esophageal pH-impedance-manometry study were
      performed. Mechanisms underlying GER and esophageal function were evaluated.
      RESULTS: Transient lower esophageal sphincter relaxation (TLESR) was the most
      common mechanism underlying GER in infants and adults (66% and 62%,
      respectively). In 66% of all GER episodes, no clearing mechanism was initiated.
      On EFT, normal motility patterns were seen in six patients (four infants, two
      adults). One of these adults had normal motility overall (>80% of swallows). Most
      swallows (78.8%) were accompanied by abnormal motility patterns. Despite this
      observation, impedance showed normal bolus transit in 40.9% of swallows. Gastric
      emptying was delayed in 57.1% of infants and 22.2% of adults. CONCLUSIONS: TLESR
      is the main mechanism underlying GER events in patients with EA. Most infants and
      adults have impaired motility, delayed bolus clearance, and delayed gastric
      emptying. However, normal motility patterns were seen in a minority of patients.

PMID- 24314194
TI  - Persistent gastrocutaneous fistula: factors affecting the need for closure.
AB  - PURPOSE: The occurrence of gastrocutaneous fistula (GCF) is a well-known
      complication after gastrostomy tube placement. We explore multiple factors to
      ascertain their impact on the rate of persistent GCF formation. METHODS: We
      retrospectively reviewed patient records for all gastrostomies (GT) constructed
      at our institution from 2007 to 2011. Association of GCF with method of
      placement, concomitant fundoplication, neurologic findings, duration of therapy,
      and demographics was evaluated using logistic regression. RESULTS: Nine hundred
      fifty patients had GTs placed, of which 148 patients had GTs removed and 47 (32%)
      of 148 required surgical closure secondary to persistent GCF. Laparoscopic and
      open procedures comprised 79 (53%) of 148 and 69 (47%) of 148, respectively.
      Seventeen (22%) patients in the laparoscopic group developed persistent GCF,
      compared to 30 (43%) in the open group (P=0.035, OR=2.52). Seventy-one patients
      had concomitant Nissen fundoplication. Thirty-one (44%) developed GCF, compared
      to 16 (21%) without a Nissen (P=0.002, OR=4.94). Patients with button in place
      for 303 days had persistent GCF incidence of 23%, compared to 45% at 540 days
      (P<0.001, OR=3.51) and 50% at 850 days (P=0.011, OR=4.51). Patients with device
      placed at 1.8 months of age were more likely to develop GCF compared to those
      with device placed at 8.9 months of age (P=0.017, OR=2.35). CONCLUSION: Open
      operations, concurrent Nissen and younger age at placement were all statistically
      significant factors causing persistent GCF.

PMID- 24314195
TI  - Pancreatic surgery in infants with Beckwith-Wiedemann syndrome and
      hyperinsulinism.
AB  - PURPOSE: To present our experience in the care of infants with Beckwith-Wiedemann
      syndrome (BWS) who required pancreatectomy for the management of severe
      Congenital Hyperinsulinism (HI). METHODS: We did a retrospective chart review of
      patients with BWS who underwent pancreatectomy between 2009 and 2012. RESULTS:
      Four patients with BWS and severe HI underwent pancreatectomy, 3 females and one
      male. Eight other BWS patients with HI could be managed medically. The diagnosis
      of BWS was established by the presence of mosaic 11p15 loss of heterozygosity and
      uniparental disomy in peripheral blood and/or pancreatic tissue. All patients had
      hypoglycemia since birth that did not respond to medical management with
      diazoxide or octreotide, and required glucose infusion rates of up to 30
      mg/kg/min. Preoperative 18-F-DOPA PET/CT scans showed diffuse uptake of the
      radiotracer throughout an enlarged pancreas in three patients and a normal sized
      pancreas with a large area of focal uptake in the pancreatic body in one patient.
      None of the patients had mutations in the ABCC8 or KCNJ1 genes that are typically
      associated with diazoxide-resistant HI. Age at surgery was 1, 2, 4, and 12 months
      and the procedures were 85%, 95%, 90%, and 75% pancreatectomy, respectively, with
      the pancreatectomy extent tailored to HI severity. Pathologic analysis revealed
      marked diffuse endocrine proliferation throughout the pancreas that occupied up
      to 80% of the parenchyma with scattered islet cell nucleomegaly. One patient had
      a small pancreatoblastoma in the pancreatectomy specimen. The HI improved in all
      cases after the pancreatectomy, with patients being able to fast safely for more
      than 8 h. All patients are under close surveillance for embryonal tumors. One
      patient developed a hepatoblastoma at age 2. CONCLUSION: The pathophysiology of
      HI in BWS patients is likely multifactorial and is associated with a dramatic
      increase in pancreatic endocrine tissue. Severe cases of HI that do not respond
      to medical therapy improve when the mass of endocrine tissue is reduced by
      subtotal or near-total pancreatectomy.

PMID- 24314196
TI  - The surgical management of insulinomas in children.
AB  - PURPOSE: Insulinomas are rare pediatric tumors for which optimal localization
      studies and management remain undetermined. We present our experience with
      surgical management of insulinomas during childhood. METHODS: A retrospective
      review was performed of patients who underwent surgical management for an
      insulinoma from 1999 to 2012. RESULTS: The study included eight patients.
      Preoperative localization was successful with abdominal ultrasound, abdominal CT,
      endoscopic ultrasound, or MRI in only 20%, 28.6%, 40%, and 50% of patients,
      respectively. Octreotide scan was non-diagnostic in 4 patients. For diagnostic
      failure, selective utilization of 18-Fluoro-DOPA PET/CT scanning, arterial
      stimulation/venous sampling, or transhepatic portal venous sampling were
      successful in insulinoma localization. Intraoperatively, all lesions were
      identified by palpation or with the assistance of intraoperative ultrasound.
      Surgical resection using pancreas sparing techniques (enucleation or distal
      pancreatectomy) resulted in a cure in all patients. Postoperative complications
      included a pancreatic fistula in two patients and an additional missed insulinoma
      in a patient with MEN-1 requiring successful reoperation. CONCLUSIONS:
      Preoperative tumor localization may require many imaging modalities to avoid
      unsuccessful blind pancreatectomy. Intraoperative palpation with the assistance
      of ultrasound offers a reliable method to precisely locate the insulinoma.
      Complete surgical resection results in a cure. Recurrent symptoms warrant
      evaluation for additional lesions.

PMID- 24314197
TI  - Component separation for complex congenital abdominal wall defects: not just for
      adults anymore.
AB  - PURPOSE: Operative repair of large abdominal wall defects in infants and children
      can be challenging. Component separation technique (CST) is utilized in adults to
      repair large abdominal wall defects but rarely used in children. The purpose of
      this report is to describe our experience with the CST in pediatric patients
      including the first description of CST use in newborns. METHODS: After IRB
      approval, we reviewed all patients who underwent CST between June 1, 2010 and
      December 31, 2012 at a large children's hospital. CST included dissection of
      abdominal wall subcutaneous tissue from the muscle and fascia and an incision of
      the external oblique aponeurosis one centimeter lateral to the rectus sheath.
      Biologic mesh onlay or underlay was used to reinforce this closure. Patients were
      followed for complications. RESULTS: Nine children, two patients with
      gastroschisis and seven with omphalocele, were repaired with CST at median
      (range) 1.1 years (5 days-10.1 years) of age. CST was the first surgical
      intervention for five children. There were minor wound complications and no
      recurrences after a median (range) follow up of 16 months (3-34 months).
      CONCLUSION: CST can be a very useful technique to repair large abdominal wall
      defects in children with a loss of abdominal domain.

PMID- 24314198
TI  - First results of a European multi-center registry of patients with anorectal
      malformations.
AB  - BACKGROUND: The European consortium on anorectal malformations (ARM-NET) was
      established to improve the health care of patients and to identify genetic and
      environmental risk factors. The aim of the present study was to present the first
      results on clinical data of a large European cohort of ARM patients based on our
      registry. METHODS: In 2010, the registry was established including patient
      characteristics and data on diagnosis, surgical therapy, and outcome regarding
      complications. Patients born between 2007 and 2012 were retrospectively added. A
      descriptive analysis of this cohort was performed. RESULTS: Two hundred and three
      ARM patients were included. Syndromes or chromosomal abnormalities were present
      in 9%. Perineal fistulas were seen most in boys (42%) and girls (29%). Rare forms
      of ARM were found in 4% of the male and in 14% of the female patients. Forty-five
      percent of the patients had additional urogenital abnormalities. However, 32% of
      the patients were never screened for bladder abnormalities. Eight percent were
      never screened for renal malformations. In the majority of patients (79%), a
      PSARP was performed for the definitive reconstruction. CONCLUSION: This
      collaborative effort provides a representative basis to estimate incidence of ARM
      types, to discuss differences and similarities in treatment, and health
      consequences throughout Europe.

PMID- 24314199
TI  - Laparoscopic-assisted pull-through for Hirschsprung's disease, a prospective
      repeated evaluation of functional outcome.
AB  - AIM OF THE STUDY: To evaluate the functional outcome of laparoscopic-assisted
      endorectal pull-through (LAP) for Hirschsprung's disease (HSCR) over time.
      METHODS: Thirty-five children with HSCR underwent laparoscopic-assisted pull
      through at our institution between 1998 and 2009. The diagnosis was
      histologically confirmed in all cases. Clinical data was extracted from the case
      records. A prospective assessment of the functional outcome was performed in 2009
      and 2012. Exclusion criteria were a follow-up of less than 6 months after
      treatment (1 case) and total colonic aganglionosis (1 case). An independent
      examiner, not involved in the clinical care of the patients, performed interviews
      using a semi-structured questionnaire. Four patients could not be traced for the
      first interview. Two cases were lost for the second interview. Altogether twenty
      seven patients completed the study. Data from the two interviews were compared.
      The regional ethical review board approved the study. MAIN RESULTS: The median
      patient age was 4 years old (range 2-16) at the time of the first interview and 7
      years old (range 5-19) at the time of the second interview . There were 23 males
      and 4 females in the study group. The median age at laparoscopic-assisted pull
      through was 104 days old (range 29 days-8 years). In the first interview 11
      patients reported constipation, 18 patients reported soiling more frequently than
      once per week when they had loose stools and 16 patients when they had solid
      stools. Laxatives or irrigations were used by 13 of the patients. In the second
      interview 4 patients reported constipation, 16 patients reported soiling when
      they had loose stools and 15 patients reported soiling when they had solid
      stools. Eight patients used laxatives or irrigations. The decrease in
      constipation was statistically significant (p=0,023). CONCLUSIONS: Our study
      shows a statistically significant reduction of constipation over time. There is a
      high risk of incontinence after laparoscopic-assisted pull-through, with few
      signs of short-term improvement.

PMID- 24314200
TI  - Natural course of undescended testes after inguinoscrotal surgery.
AB  - PURPOSE: The purpose of the study is to study the natural course of undescended
      testes after inguinoscrotal surgery. METHODS: From 2003-2010, 24 boys were
      observed with 26 undescended testes after inguinoscrotal surgery; 12 had
      previously undergone inguinal hernia repair and 12 orchidopexy. Spontaneous
      descent was awaited and (re-)orchidopexy would only be performed in case of non
      descent at puberty. The boys were assessed annually for testis position and for
      testis volume as measured by ultrasound. RESULTS: At the end of the study period,
      19 testes had reached scrotal position; of these, 13 (68%) had descended
      spontaneously and 6 (32%) had been (re-)orchidopexied. No difference was found in
      the rate of spontaneous descent after previous orchidopexy or inguinal hernia
      repair (P=0.419). CONCLUSION: Spontaneous descent of undescended testes after
      inguinoscrotal surgery occurs regularly. In this study, it was observed in two
      out of every three cases.

PMID- 24314201
TI  - The effect of platelet rich fibrin on growth factor levels in urethral repair.
AB  - AIM: Platelet rich fibrin (PRF) is an autologous source of growth factors and
      promotes wound healing. An experimental study was performed to evaluate the
      effect of PRF on growth factor levels in urethral repair. MATERIALS AND METHODS:
      Eighteen Wistar albino rats were included in the study. Rats were allocated in
      three groups (n:6): control (CG), sham (SG), and PRF (PRFG). In SG, a 5 mm
      vertical incision was performed in the penile urethra and repaired with 10/0
      Vicryl(r) under a microscope. In PRFG, during the urethral repair as described in
      SG, 1 cc of blood was sampled from each rat and centrifuged for 10 minutes at
      2400 rpm. PRF obtained from the centrifugation was placed on the repair site
      during closure. Penile urethras were sampled 24 hours after PRF application in
      PRFG and after urethral repair in SG. Transforming growth factor beta receptor
      (TGF-beta-R-CD105), vascular endothelial growth factor (VEGF) and its receptor
      (VEGF-R), as well as endothelial growth factor receptor (EGFR), were evaluated in
      subepithelia of the penile skin and urethra. Groups were compared for growth
      factor levels and growth factor receptor expression with the Kruskal Wallis test.
      RESULTS: TGF-beta-R levels were significantly decreased in SG when compared to CG
      (p<0.05). In PRFG, TGF-beta-R was increased in both subepithelia of penile skin
      and urethra with respect to SG (p<0.05). When VEGF levels and its receptor
      expression were compared between SG and PRFG, VEGF levels were found to be
      increased in penile skin subepithelium, whereas VEGF-R expressions were decreased
      in urethral subepithelia in PRFG (p<0.05). There was no difference between groups
      for EGFR levels (p>0.05). CONCLUSION: Use of PRF after urethral repair increases
      TGF-beta-R and VEGF expressions in urethral tissue. PRF can be considered as an
      alternative measure to improve the success of urethral repair.

PMID- 24314202
TI  - Inhibition of synovitis and joint destruction by a new single domain antibody
      specific for cyclophilin A in two different mouse models of rheumatoid arthritis.
AB  - INTRODUCTION: Cyclophilin A (CypA) is implicated in rheumatoid arthritis (RA)
      pathogenesis. We studied whether a novel anti-CypA single domain antibody (sdAb)
      treatment would modulate the severity of the disease in two different animal
      models of RA. METHODS: A novel sdAb, named sdAbA1, was screened from an immunized
      camel sdAb library and found to have a high binding affinity (KD = 6.9 * 10-9 M)
      for CypA. The SCID-HuRAg model and the collagen-induced arthritis (CIA) in mice
      were used to evaluate the effects of sdAbA1 treatment on inflammation and joint
      destruction. For in vitro analysis, monocytes/macrophages were purified from
      synovial fluid and peripheral blood of patients with RA and were tested for the
      effect of anti-CypA sdAb on metalloproteinase (MMP) production. Human monocyte
      cell line THP-1 cells were selected and western blot analyses were performed to
      examine the potential signaling pathways. RESULTS: In the CIA model of RA, the
      sdAbA1 treatment resulted in a significant decrease in clinical symptoms as well
      as of joint damage (P <0.05). In the SCID-HuRAg model, treatment with anti-CypA
      antibody sdAbA1 significantly reduced cartilage erosion, inflammatory cell
      numbers and MMP-9 production in the implanted tissues (P <0.05). It also
      significantly reduced the levels of human inflammatory cytokines IL-6 and IL-8 in
      mouse serum (P <0.05). No toxic effects were observed in the two animal models.
      In vitro results showed that sdAbA1 could counteract CypA-dependent MMP-9
      secretion and IL-8 production by interfering with the ERK-NF-kappaB pathway.
      CONCLUSIONS: Blockade of CypA significantly inhibited synovitis and
      cartilage/bone erosion in the two tested animal models of RA. Our findings
      provide evidence that sdAbA1 may be a potential therapeutic agent for RA.

PMID- 24314203
TI  - Impact of left ventricular geometry on long-term survival in elderly men and
      women.
AB  - BACKGROUND: Adverse loading conditions and cardiac injury lead to remodelling of
      the heart into different patterns of left ventricular (LV) geometry. Geometry can
      be classified into LV hypertrophy (LVH), concentric remodelling (CR) or normal
      geometry (NG). The prognostic implications of the different geometric patterns
      have been extensively studied in middle-aged subjects, but data are scarcer for
      elderly populations. METHODS: From a community-based random sample of 75-year-old
      men and women, subjects with normal LVEF were selected (n = 303). All-cause and
      cardiovascular mortality was analysed by LV geometry with Cox regression
      (unadjusted and adjusted for sex, prevalent hypertension, smoking, diabetes and
      prevalent ischaemic heart disease). Median follow-up time was 9.9 years. RESULTS:
      Prevalence of CR and LVH was 19% and 17%, respectively. Hazard ratios (HRs) for
      CR were 0.93 (95% CI 0.54-1.58) for all-cause and 1.13 (0.48-2.65) for
      cardiovascular mortality. HRs for LVH were 2.01 (1.30-3.10) for all-cause and
      3.55 (1.89-6.67) for cardiovascular mortality. As non-proportionality was present
      in the form of an increasing hazard for LVH, we partitioned the follow-up time at
      the median event time (approximately 7 years) and performed Cox regression
      separately within each time period. HRs for LVH during the first period were 1.23
      (0.63-2.42) for all-cause and 1.79 (0.69-4.65) for cardiovascular mortality,
      while HRs for the second period were 3.06 (1.73-5.41) for all-cause and 6.60
      (2.82-15.39) for cardiovascular mortality. CONCLUSION: In this community-based
      sample of 75-year-old men and women with normal LVEF, LVH was associated with an
      adverse prognosis during long-term follow-up, whereas CR was not.

PMID- 24314204
TI  - Exploratory randomized controlled trial evaluating the impact of a waiting list
      control design.
AB  - BACKGROUND: Employing waiting list control designs in psychological and
      behavioral intervention research may artificially inflate intervention effect
      estimates. This exploratory randomized controlled trial tested this proposition
      in a study employing a brief intervention for problem drinkers, one domain of
      research in which waiting list control designs are used. METHODS: All
      participants (N = 185) were provided with brief personalized feedback
      intervention materials after being randomly allocated either to be told that they
      were in the intervention condition and that this was the intervention or to be
      told that they were in the waiting list control condition and that they would
      receive access to the intervention in four weeks with this information provided
      in the meantime. RESULTS: A total of 157 participants (85%) were followed-up
      after 4 weeks. Between-group differences were found in one of four outcomes
      (proportion within safe drinking guidelines). An interaction was identified
      between experimental manipulation and stage of change at study entry such that
      participant change was arrested among those more ready to change and told they
      were on the waiting list. CONCLUSIONS: Trials with waiting list control
      conditions may overestimate treatment effects, though the extent of any such bias
      appears likely to vary between study populations. Arguably they should only be
      used where this threat to valid inference has been carefully assessed.

PMID- 24314205
TI  - Summer Meeting 2013: growth and physiology of bifidobacteria.
AB  - Bifidobacteria are a minor fraction of the human colon microbiota with
      interesting properties for carbohydrate degradation. Monosaccharides such as
      glucose and fructose are degraded through the bifid shunt, a dedicated pathway
      involving phosphoketolase activity. Its stoechiometry learns that three moles of
      acetate and two moles of lactate are produced per two moles of glucose or
      fructose that are degraded. However, deviations from this 3 : 2 ratio occur,
      depending on the rate of substrate consumption. Slower growth rates favour the
      production of acetate and pyruvate catabolites (such as formate) at the cost of
      lactate. Interestingly, bifidobacteria are capable to degrade inulin-type
      fructans (ITF) (oligofructose and inulin) and arabinoxylan-oligosaccharides
      (AXOS). Beta-fructofuranosidase activity enables bifidobacteria to degrade ITF.
      However, this property is strain-dependent. Some strains consume both fructose
      and oligofructose, with different preferences and degradation rates. Small
      oligosaccharides (degree of polymerization or DP of 2-7) are taken up, in a
      sequential order, indicating intracellular degradation and as such giving these
      bacteria a competitive advantage towards other inulin-type fructan degraders such
      as lactobacilli, bacteroides and roseburias. Other strains consume long fractions
      of oligofructose and inulin. Exceptionally, oligosaccharides with a DP of up to
      20 (long-chain inulin) are consumed by specific strains. Also, the degradation of
      AXOS by alpha-arabinofuranosidase and beta-xylosidase is strain-dependent.
      Particular strains consume the arabinose substituents, whether or not together
      with a consumption of the xylose backbones of AXOS, either up to xylotetraose or
      higher and either extra- or intracellularly. The production of high amounts of
      acetate that accompanies inulin-type fructan degradation by bifidobacteria cross
      feeds other colon bacteria involved in the production of butyrate. However,
      bifidobacterial strain-dependent differences in prebiotic degradation indicate
      the existence of niche-specific adaptations and hence mechanisms to avoid
      competition among each other and to favour coexistence with other colon bacteria.

PMID- 24314206
TI  - Integrating gene and protein expression data with genome-scale metabolic networks
      to infer functional pathways.
AB  - BACKGROUND: The study of cellular metabolism in the context of high-throughput 
      omics data has allowed us to decipher novel mechanisms of importance in
      biotechnology and health. To continue with this progress, it is essential to
      efficiently integrate experimental data into metabolic modeling. RESULTS: We
      present here an in-silico framework to infer relevant metabolic pathways for a
      particular phenotype under study based on its gene/protein expression data. This
      framework is based on the Carbon Flux Path (CFP) approach, a mixed-integer linear
      program that expands classical path finding techniques by considering additional
      biophysical constraints. In particular, the objective function of the CFP
      approach is amended to account for gene/protein expression data and influence
      obtained paths. This approach is termed integrative Carbon Flux Path (iCFP). We
      show that gene/protein expression data also influences the stoichiometric
      balancing of CFPs, which provides a more accurate picture of active metabolic
      pathways. This is illustrated in both a theoretical and real scenario. Finally,
      we apply this approach to find novel pathways relevant in the regulation of
      acetate overflow metabolism in Escherichia coli. As a result, several targets
      which could be relevant for better understanding of the phenomenon leading to
      impaired acetate overflow are proposed. CONCLUSIONS: A novel mathematical
      framework that determines functional pathways based on gene/protein expression
      data is presented and validated. We show that our approach is able to provide new
      insights into complex biological scenarios such as acetate overflow in
      Escherichia coli.

PMID- 24314208
TI  - Selection, p53, and pigmentation.

PMID- 24314207
TI  - The neurological disease ontology.
AB  - BACKGROUND: We are developing the Neurological Disease Ontology (ND) to provide a
      framework to enable representation of aspects of neurological diseases that are
      relevant to their treatment and study. ND is a representational tool that
      addresses the need for unambiguous annotation, storage, and retrieval of data
      associated with the treatment and study of neurological diseases. ND is being
      developed in compliance with the Open Biomedical Ontology Foundry principles and
      builds upon the paradigm established by the Ontology for General Medical Science
      (OGMS) for the representation of entities in the domain of disease and medical
      practice. Initial applications of ND will include the annotation and analysis of
      large data sets and patient records for Alzheimer's disease, multiple sclerosis,
      and stroke. DESCRIPTION: ND is implemented in OWL 2 and currently has more than
      450 terms that refer to and describe various aspects of neurological diseases. ND
      directly imports the development version of OGMS, which uses BFO 2. Term
      development in ND has primarily extended the OGMS terms 'disease', 'diagnosis',
      'disease course', and 'disorder'. We have imported and utilize over 700 classes
      from related ontology efforts including the Foundational Model of Anatomy,
      Ontology for Biomedical Investigations, and Protein Ontology. ND terms are
      annotated with ontology metadata such as a label (term name), term editors,
      textual definition, definition source, curation status, and alternative terms
      (synonyms). Many terms have logical definitions in addition to these annotations.
      Current development has focused on the establishment of the upper-level structure
      of the ND hierarchy, as well as on the representation of Alzheimer's disease,
      multiple sclerosis, and stroke. The ontology is available as a version-controlled
      file at http://code.google.com/p/neurological-disease-ontology along with a
      discussion list and an issue tracker. CONCLUSION: ND seeks to provide a formal
      foundation for the representation of clinical and research data pertaining to
      neurological diseases. ND will enable its users to connect data in a robust way
      with related data that is annotated using other terminologies and ontologies in
      the biomedical domain.

PMID- 24314209
TI  - A multi-centre phase IIa clinical study of predictive testing for preeclampsia:
      improved pregnancy outcomes via early detection (IMPROvED).
AB  - BACKGROUND: 5% of first time pregnancies are complicated by pre-eclampsia, the
      leading cause of maternal death in Europe. No clinically useful screening test
      exists; consequentially clinicians are unable to offer targeted surveillance or
      preventative strategies. IMPROvED Consortium members have pioneered a
      personalised medicine approach to identifying blood-borne biomarkers through
      recent technological advancements, involving mapping of the blood metabolome and
      proteome. The key objective is to develop a sensitive, specific, high-throughput
      and economically viable early pregnancy screening test for pre-eclampsia.
      METHODS/DESIGN: We report the design of a multicentre, phase IIa clinical study
      aiming to recruit 5000 low risk primiparous women to assess and refine innovative
      prototype tests based on emerging metabolomic and proteomic technologies.
      Participation involves maternal phlebotomy at 15 and 20 weeks' gestation, with
      optional testing and biobanking at 11 and 34 weeks. Blood samples will be
      analysed using two innovative, proprietary prototype platforms; one metabolomic
      based and one proteomic based, both of which outperform current biomarker based
      screening tests at comparable gestations. Analytical and clinical data will be
      collated and analysed via the Copenhagen Trials Unit. DISCUSSION: The IMPROvED
      study is expected to refine proteomic and metabolomic panels, combined with
      clinical parameters, and evaluate clinical applicability as an early pregnancy
      predictive test for pre-eclampsia. If 'at risk' patients can be identified, this
      will allow stratified care with personalised fetal and maternal surveillance,
      early diagnosis, timely intervention, and significant health economic savings.
      The IMPROvED biobank will be accessible to the European scientific community for
      high quality research into the cause and prevention of adverse pregnancy outcome.
      TRIAL REGISTRATION: Trial registration number NCT01891240The IMPROvED project is
      funded by the seventh framework programme for Research and Technological
      development of the EU. http://www.fp7-improved.eu/

PMID- 24314211
TI  - [The primary tumor target displacement and its impact during radiotherapy of
      esophageal cancer].

PMID- 24314210
TI  - Allergen immunotherapy and allergic rhinitis: false beliefs.
AB  - BACKGROUND: Over the last 100 years, several persistent misconceptions or 'false
      beliefs' have built up around allergen immunotherapy and its use in allergic
      rhinitis. This is perhaps because enthusiastic physicians administered complex
      allergen extracts to a diverse population of patients suffering from
      heterogeneous atopic conditions. Here, we review evidence that counters seven of
      these 'false beliefs.' DISCUSSION: 1. The symptoms of allergic rhinitis can be
      more heterogeneous, more severe and more troublesome in everyday life than many
      physicians believe. Large-scale epidemiological surveys show that the majority of
      allergic rhinitis patients have at least one symptom severe enough to interfere
      with sleep quality, productivity and/or well-being. 2. Allergen immunotherapy is
      not necessarily suitable for all allergic rhinitis patients (notably those with
      mild symptoms). Recent evidence from double-blind, placebo-controlled, randomized
      clinical trials suggests that the more severe the disease, the greater the
      treatment effect. 3. Allergen immunotherapy is often accused of lack of efficacy
      (relative to pharmacotherapy, for example). However, there are now many meta
      analyses, systematic reviews and high-quality clinical trials that find
      overwhelmingly in favor of the efficacy of allergen immunotherapy (including
      sublingual formulations) in allergic rhinitis induced by pollen and,
      increasingly, other allergens. 4. Natural-exposure and challenge-chamber trials
      have shown that symptom relief may become apparent within months or even weeks of
      the initiation of allergen immunotherapy. 5. In pollen-induced allergic rhinitis,
      several years of subcutaneous or sublingual allergen immunotherapy are associated
      with sustained clinical efficacy after subsequent treatment cessation -
      confirming the disease-modifying nature of this therapy. 6. Most patients seeking
      treatment for allergic rhinitis are polysensitized, and allergen immunotherapy
      has proven efficacy in large, robust clinical trials in these groups.
      Polysensitization is not a contraindication to allergen immunotherapy. 7.
      Sublingual allergen immunotherapy is safe for home administration. A recent
      review calculated that 1 billion doses were administered worldwide between 2000
      and 2010 and found that the 11 case reports of anaphylaxis (all non-fatal)
      corresponded to non-standard practice. SUMMARY: Modern, evidence-based medicine
      has generated more than enough robust evidence to remove misconceptions about
      allergen immunotherapy and allergic rhinitis.

PMID- 24314212
TI  - [Comparison of the targeting properties of 2-deoxy-D-glucose-conjugated
      nanoparticles to breast cancer MDA-MB-231 cells and breast fibroblasts cells].
AB  - OBJECTIVE: To compare the differences in uptake of 2-deoxy-D-glucose (2-DG)
      conjugated nanoparticles between breast carcinoma MDA-MB-231 cells with high
      metabolism and breast fibroblasts with normal metabolism, and investigate the
      feasibility of using the coated nanoparticles as a MRI-targeted contrast agent
      for highly metabolic carcinoma cells. METHODS: The gamma-Fe2O3@DMSA-DG was
      prepared. The glucose metabolism level of both cell lines was determined. The
      targeting efficacy of gamma-Fe2O3@DMSA-DG and gamma-Fe2O3@DMSA NPs to breast
      carcinoma MDA-MB-231 cells and breast fibroblasts at 10 min, 30 min, 1 h and 2 h
      was measured with Prussian blue staining and UV colorimetric assay. MRI was
      performed to visualize the changes of T2WI signal intensity. RESULTS: Prussian
      blue staining showed more intracellular blue granules in the MDA-MB-231 cells of
      gamma-Fe2O3@DMSA-DG NPs group than that in the gamma-Fe2O3@DMSA NPs group, and
      the gamma-Fe2O3@DMSA-DG uptake was greatly competed by free D-glucose. As
      revealed by UV colorimetric assay, MDA-MB-231 cells also showed that the cellular
      iron amount of gamma-Fe2O3@DMSA-DG group was significantly higher than that of
      the gamma-Fe2O3@DMSA group and gamma-Fe2O3@DMSA-DG + D-glucose group,
      statistically with a significant difference between them. MRI showed that the
      signal intensity of gamma-Fe2O3@DMSA-DG group was decrease significantly, the T2
      signal intensity was decreased by 10.5%, 37.5%, 72.9%, 92.0% for 10 min, 30 min,
      1 h and 2 h, respectively. In contrast, the signal intensity did not show obvious
      decrease in the gamma-Fe2O3@DMSA-DG group, the T2 signal intensity was decreased
      by 8.5%, 11.4%, 32.0%, 76.7% for 10 min, 30 min, 1 h and 2 h, respectively.
      However, HUM-CELL-0056 cells did not produce apparent difference for positive
      staining in the gamma-Fe2O3@DMSA-DG group, gamma-Fe2O3@DMSA group and gamma
      Fe2O3@DMSA-DG+D-glucose group, and the signal intensity also did not produce
      apparent difference. CONCLUSIONS: gamma-Fe2O3@DMSA-DG has good targeting ability
      to highly metabolic breast carcinoma (MDA-MB-231) cells. It is feasible to serve
      as a specific MRI-targeted contrast agent for highly metabolic carcinoma cells,
      and deserves further studies in vivo.

PMID- 24314214
TI  - [Overexpression of p-Stat3 and Mcl-1, and their correlation with differentiation
      and apoptotic resistance in esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To detect the expression of phosphorylated-signal transducer and
      activator of transcription 3 (p-Stat3) and myeloid leukemia-1 (Mcl-1) as well as
      their correlation, and to investigate the functional role of Stat3 and Mcl-1 in
      the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: Stat3
      activity in ESCC cells was inhibited with JAK/Stat3 inhibitors (AG490 or JSI
      124). Specific siRNA was used to inhibit the Stat3 expression. Cell apoptosis was
      detected by flow cytometry. Expression of Mcl-1 protein was determined by Western
      blotting. Expression of phospho-Stat3 (Tyr705) and myeloid leukemia-1 (Mcl-1)
      proteins in ESCC tissues was detected by tissue microarray and
      immunohistochemistry. The relationship between p-Stat3 or Mcl-1 aberrant
      expression and clinicopatholohical features of ESCC was analyzed. The correlation
      of their expression was also analyzed. RESULTS: Suppression of the Stat3
      signaling activation in ESCC cells led to marked apoptosis, and dramatic
      reduction of Mcl-1 protein. The positive rate of phospho-Stat3 (Tyr705)
      expression was 45.0% in 50/111 of the ESCC tissue samples. The lower the degree
      of tumor differentiation, the higher the positive rate of phospho-Stat3 (Tyr705),
      showing a significant difference (P = 0.018). The positive rate of Mcl-1 protein
      expression was 72.1% (80/111), and the lower the degree of tumor differentiation
      was, the higher there was the positive rate of Mcl-1, with a significant
      difference (P = 0.026). There was a positive correlation between the expressions
      of p-Stat3 and Mcl-1 proteins (P = 0.012). CONCLUSIONS: In a subset of ESCC
      tissues, p-Stat3 (Tyr705) and Mcl-1 are overexpressed and positively correlated
      with each other, and both are correlated with tumor differentiation. Persistent
      activation of Stat3 contributes to apoptotic resistance in ESCC cells, and may be
      at least partly mediated through upregulation of Mcl-1.

PMID- 24314213
TI  - [Effects of AG1478 on the expression of FOXM1 gene via FOXO3a in non-small cell
      lung cancer cells].
AB  - OBJECTIVE: To explore the effects of EGFR-TKI AG1478 on the expression of FoxMl
      and FOXO3a genes in non-small cell cancer (NSCLC) cell lines, and explore the
      effect on cell proliferation and drug sensitivity to AG1478 after down-regulation
      of FOXMl and FOXO3a expression by RNAi technique. METHODS: Human lung cancer
      cells were treated with AG1478 at different concentrations. RT-PCR and Western
      blot were used to examine the expression of P-EGFR, FOXM1, FOXO3a mRNA and
      protein. After transient transfection of FOXM1 and FOXO3a siRNA, RT-PCR and
      Western blot were employed to determine the transfection efficiency and
      expression of the related proteins. CCK-8 assay, colony formation assay and flow
      cytometry were performed to evaluate the cell proliferation, colony formation
      ability and the changes in cell cycle distribution. RESULTS: The expressions of
      FOXM1 mRNA and protein were inhibited by AG1478 in a dose-dependent manner (both
      P < 0.05). After transfection with FOXM1 siRNA, the expressions of FOXM1 mRNA and
      protein, and proteins of cyclin B1, c-Myc, and Bcl-2 were significantly down
      regulated, and the expressions of p21 and cleaved-PARP proteins were
      significantly up-regulated (all P < 0.05). The colony number of FOXM1siRNA
      transfection group was 37.3 +/- 8.6, significantly lower than that of the blank
      control (135.3 +/- 7.0) and negative control group (125.3 +/- 7.5, P < 0.05). The
      colony formation inhibition rate was (7.40 +/- 0.94)% in the negative control
      group and (72.4 +/- 6.09)% in the FOXM1 siRNA transfection group. FOXM1siRNA
      transfection induced cell cycle arrest at G2/M phase with a percentage of (55.6
      +/- 4.83)%, significantly higher than that of the blank control [(24.30 +/-
      1.95)%] and negative control group [(21.3 +/- 2.06)%, P < 0.05]. Additionally,
      the FOXM1siRNA transfection significantly increased the chemosensitivity of A549
      cells to AG1478 (P < 0.05). Besides, AG1478 induced expression and nuclear
      relocation of FOXO3a. After the FOXO3a siRNA transfection, the expression of
      FOXM1 protein was significantly up-regulated, and resulted in a reduction of
      AG1478-induced inhibition of FOXM1. CONCLUSIONS: The expression of FOXM1 is down
      regulated by AG1478 via FOXO3a in the NSCLC cell lines, and then increases the
      chemosensitivity of A549 cells to AG1478. It suggests that FOXM1 could be a
      potential target for the therapy and drug exploitation for NSCLC.

PMID- 24314215
TI  - [Detection of EGFR and K-ras mutations in non-small cell lung cancer using
      cytological specimens].
AB  - OBJECTIVE: To validate the feasibility for detecting EGFR and k-ras mutations
      using cytological specimens. METHODS: Cytological specimens including fine-needle
      aspiration (FNA), pleural effusion (PLE) and fiberoptic bronchoscopic (FOB)
      brushing were collected from patients with non-small cell lung cancer (NSCLC )
      from January 2011 to July 2011 at the Department of Cytology, Cancer Hospital,
      Chinese Academy of Medical Sciences (CHCAMS). Polymerase chain reaction (PCR) was
      carried out to amplify EGFR exons 18-21 and k-ras codons 12-13, and then the PCR
      products sequencing and analysis were performed. RESULTS: Fifty cytological
      specimens were collected including 19 cases of FOB, 9 cases of FNA, 22 cases of
      PLE. Of them DNA was successfully extracted in 43 cases, and specific PCR
      amplification products sequencing were performed in 42 cases. EGFR mutations were
      detected in 14 of 42 specimens (33.3%), the frequencies of EGFR mutations in
      exons 19, 20 and 21 were 16.7% (7/42), 4.8% (2/42) and 11.9% (5/42),
      respectively, and no mutation was found in exon 18. Higher frequencies of EGFR
      mutations were detected in exons 19 and 21 (85.7%). Mutations were identified in
      38.7% (12/31) cases of adenocarcinoma. K-ras mutations were found in 2 of 42
      specimens (4.8%). EGFR and K-ras mutations were not found in the same case.
      CONCLUSIONS: Cytological specimens are feasible for detecting EGFR and K-ras
      mutation. This is especially beneficial in patients in whom histological
      materials can not be obtained.

PMID- 24314216
TI  - [Effect of miRNA-106a expression on the prognosis of patients with esophageal
      squamous cell carcinoma].
AB  - OBJECTIVE: To study the expression of miRNA-106a gene in esophageal squamous cell
      carcinoma (ESCC) and its association with clinicopathological features and
      prognosis of ESCC patients. METHODS: Real-time fluorescence quantitative
      polymerase chain reaction (PCR) assay was used to determine the expression of
      miRNA-106a gene in esophageal cancer tissue and corresponding normal mucosa of 81
      cases. Immunohistochemical technique was applied to detect the expression of p53,
      human epidermal growth factor receptor 2 (HER-2), DNA topoisomerase II (Topo II)
      and multidrug resistance-associated protein (MRP). The association of miRNA-106a
      expression with clinicopathological features, expression of related proteins, and
      prognosis of the patients was analyzed. RESULTS: Among the 81 cases, under
      expression of miRNA-106a gene was found in 48 cases (59.3%), normal expression in
      22 cases (27.2%), and overexpression in 11 cases (13.6%). The expression of miRNA
      106 gene was significantly associated with lymph node metastasis, pathological
      stage, and nerve invasion (all P < 0.05), significantly associated with
      expression of p53 (P = 0.006), and not significantly associated with expressions
      of HER-2, Topo II and MRP proteins (all P > 0.05). The expression of miRNA-106a
      gene was also significantly associated with progression-free survival (PFS, P =
      0.032), but not significantly with overall survival (OS, P = 0.486). The results
      of Cox multivariate regression analysis showed that the PFS of ESCC patients was
      significantly correlated with lymph node metastasis (P = 0.029), but not
      correlated with the age, gender, tumor length, T stage, degree of
      differentiation, nerve invasion, and miRNA-106a expression (all P > 0.05).
      CONCLUSIONS: In esophageal squamous cell carcinomas, the miRNA-106a gene is under
      expressed, with tumor suppressor function, and may be regarded as a biological
      marker to assess the prognosis in patients with esophageal squamous cell
      carcinoma.

PMID- 24314217
TI  - [Evaluation of the prognostic significance of refinement and stratification of
      distant metastasis status in 1016 cases of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the prognostic factors for nasopharyngeal carcinoma
      (NPC) with different metastatic status, and to improve the NPC management by
      multi-level refinement and stratification of M1 stage distant metastases.
      METHODS: Clinicopathological data of 1016 NPC patients with distant metastases
      were retrospectively reviewed. The M1 stage distant metastases were subdivided
      into synchronous or metachronous metastases, metastatic sites (lung, bone,
      liver), number of metastatic organs (solitary, multiple) and number of metastases
      (solitary, multiple) subgroups to analyze the prognosis and survival of the
      patients. RESULTS: The most frequently involved metastatic sites were bone (542,
      53.3%), lung (420, 41.3%) and liver (302, 29.7%). There were solitary metastatic
      lesions in 164 patients (16.2%), synchronous metastases in 376 cases and
      metachronous metastases in 640 cases. The median overall survival of the whole
      group of 1016 NPC patients was 30.8 months since the time of diagnosis of
      metastasis. For the 376 patients in the synchronous metastasis group, the median
      survival was 23.3 months and the 1-, 3- and 5-year overall survival rates were
      74.2%, 27.6% and 18.5%, respectively. For the 640 patients in the metachronous
      metastases group, the median survival was 36.7 months, and the 1-, 3- and 5-year
      overall survival rates were 88.1%, 49.6% and 28.6%, respectively, with a
      significant difference between the two groups (all P < 0.001). Cox multivariate
      analysis indicated that the number of metastatic lesions, different metastatic
      sites and N stage at initial diagnosis were independent prognostic factors for
      patients with metachronous metastases (P < 0.05). CONCLUSIONS: A theory of
      detailed multi-level metastasis (M1) stratification aiming at different distant
      metastasis status for nasopharyngeal carcinoma is proposed. To take appropriate
      individualized treatment scheme according to the prognosis and expected survival
      should be helpful to improving the diagnosis and treatment of nasopharyngeal
      cancer.

PMID- 24314218
TI  - [Association of promoter methylation of ERp57 gene with the pathogenesis of
      cervical lesions in Uighur women].
AB  - OBJECTIVE: To investigate the relationship and significance between endoplasmic
      reticulum protein 57 (ERp57) gene promoter region methylation with the
      pathogenesis of cervical lesions in Uighur women. METHODS: The special software
      was used to design specific primers of CpG island fragments of ERp57 gene
      promoter and bisulfite-modified SiHa cancer cell DNA for PCR amplification,
      cloning and sequencing the target fragments to obtain relevant information of CpG
      methylation in the gene base sequencs. Seventy-eight fresh tissues of CIN, CSCC
      and normal control were collected, and the methylation level of ERp57 gene
      promoter regions in different cervical lesions were identified using Sequenom
      MassARRAY(DNA) technology. RESULTS: ERp57 gene corresponding target fragment
      contained the 18 CpG sites. All of the CpG sites methylation occurred in SiHa
      cervical cancer cell genomic DNA. The analysis of the data resulted from the
      quantitative analysis of single CpG site methylation by Sequenom MassARRAY
      platform showed that the methylation level between three CpG sites (CpG_1, CpG_5
      and CpG_7) from CpG_1, CpG_2, CpG_3.4, CpG_5, CpG_6, CpG_7, CpG_8 and CpG_ 9 had
      significant differences in the CSCC, CIN or control groups. CONCLUSIONS: Although
      the global methylation level of the ERp57 gene promoter is higher in CSCC than
      that in CIN and normal control tissues in Uighur women, hypermethylation occurs
      only in certain CpG islands and sites. This indicates that the regulation of
      expression by DNA methylation is not CpG island-specific, but varies for
      individual CpG sites, and may explain to a certain extent the epigenetic
      mechanisms regulated by Erp57 gene expression.

PMID- 24314219
TI  - [Efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the
      treatment of metastatic colorectal cancer, mCRC].
AB  - OBJECTIVE: To assess the efficacy and safety of bevacizumab (BEV) plus
      chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).
      METHODS: Seventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or
      irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related
      adverse reactions were observed. The efficacy assessment was conducted after at
      least 2 cycles of BEV therapy. The adverse reactions were recorded in each
      therapy cycle. Among the 77 cases, 64 patients had finished the efficacy
      assessment. The adverse reactions in all patients were assessed. RESULTS: The
      overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64),
      and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received
      the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR
      was 85.2%. Four patients with potentially resectable lesions became resectable
      after the regimen and received R0 resection of the liver metastases successfully.
      Twenty-five patients who received the regimen as second line therapy had poor
      result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8
      cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings
      occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of
      epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of
      grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2),
      and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case
      (0.3%). In two patients who had incomplete intestinal obstruction history
      appeared exacerbated intestinal obstruction symptoms after the application of BEV
      plus CPT11 regimen. CONCLUSIONS: BEV plus chemotherapy regimen as first-line
      treatment can improve the ORR and DCR of mCRC patients. When it was used as
      second- or later-line therapy, it may display satisfied DCR, although with a poor
      efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.

PMID- 24314220
TI  - [Feasibility and safety of CT-guided percutaneous needle biopsy and subsequent
      iodine-125 seed interstitial implantation for pancreatic cancer].
AB  - OBJECTIVE: To discuss the feasibility and safety of different approaches for CT
      guided percutaneous needle biopsy and subsequent iodine-125 seed interstitial
      implantation for pancreatic cancer. METHODS: A retrospective study was carried
      out on the complete data of 35 patients with pancreatic cancer who have received
      CT-guided percutaneous needle biopsy with or without subsequent iodine-125 seed
      interstitial implantation. There were 9 lesions located in the head of pancreas,
      20 located in the body, and 6 in the tail. The maximum diameter of the lesions
      varied from 12 mm to 60 mm (mean 37.1 mm). The patients were treated with a
      needle in diameter of 16-21G. Operations were undertaken via anterior, posterior
      and lateral approaches. RESULTS: Thirty-five patients underwent 43 times of CT
      guided percutaneous needle biopsies. Thirty-one cases were pathologically
      diagnosed as cancer, 2 cases inflammatory lesions, and 2 were suspected tumors
      (one of which was finally diagnosed as cancer, while another was pancreatic
      pseudocyst). The ratio of correct diagnosis was 94.3%. Fourteen patients were
      treated subsequently with CT-guided iodine-125 seed interstitial implantation
      therapy, with a total of 65 times of needle puncture. The operations were
      performed via direct approach to the tumor in 18 cases, transhepatic approach in
      2 cases, transgastric approach in 4 cases, transintestinal approach in 10 cases,
      and through mesenteric vessels in one case. Incidence of complications in the
      biopsy group was 2.32% (1/43), and in the implantation group was 6.15% (4/65),
      with a statistically non-significant difference (P = 0.600) between the two
      groups. Incidence of complications in the group using 16-18G needle was 4.65%
      (4/86), while in the group using 20-21G needle was 4.55% (1/22), also with a non
      significant difference (P = 0.064). The accuracy rate of needle biopsy in this
      study was 94.28% (33/35). CONCLUSION: CT-guided percutaneous needle biopsy and
      subsequent iodine-125 seed interstitial implantation are both feasible and safe
      for pancreatic cancer.

PMID- 24314221
TI  - [Extrahepatic collateral arteries are involved in the blood supply to
      hepatocellular carcinoma: angiographic demonstration and transcatheter arterial
      chemoembolization].
AB  - OBJECTIVE: To evaluate the incidence of extrahepatic collateral arteries involved
      in the blood supply to hepatocellular carcinoma (HCC) and to assess the technical
      success rates and complications of transcatheter arterial chemoembolization
      (TACE) through the collaterals. METHODS: 1356 TACE procedures were performed in
      874 consecutive patients through extrahepatic collateral pathways to HCC between
      August 2006 and August 2010 in our department. The extrahepatic collateral
      pathways to HCC revealed on angiography were retrospectively evaluated. TACE
      through extrahepatic collaterals using iodized oil and gelatin sponge particles
      was performed when a catheter was advanced into the feeding branch to avoid
      nontarget embolization. RESULTS: Incidences of collateral source to HCC were
      76.3% from the right inferior phrenic artery (RIPA), 2.4% from the left inferior
      phrenic artery (LIPA), 6.9% from the right and 0.4% from the left internal
      mammary arteries (RIMA, LIMA), 2.9% from the right intercostal artery (RICA),
      2.0% from the omental artery, 0.8% from the right or middle colic artery, 2.3%
      from the cystic artery, 1.3% from the left and 1.1% from the right gastric
      arteries (LGA, RGA), 3.5% from the right renal capsular artery (RRCA), right
      middle adrenal artery (RMAA) and right inferior adrenal artery (IAA). Technical
      success rates of TACE were 95.9% in the RIPA, 93.8% in the LIPA, 100.0% in the
      RIMA and LIMA, 55.0% in the RICA, 77.8% in the omental artery, 63.6% in the colic
      artery, 67.7% in the cystic artery, 76.5% in the LGA, 73.3% in the RGA and 95.8%
      in the RRCA, RMAA, and RIAA. Complications included skin erythema and necrosis
      after TACE through the RIMA, skin erythema after TACE through the RICA,
      cholecystitis after TACE through the cystic artery (n = 1), and pleural effusion,
      basal atelectasis and hiccup after TACE through the IPA. CONCLUSION: TACE through
      extrahepatic collaterals is safe and feasible, and with a high success rate in
      the treatment of hepatocellular carcinoma.

PMID- 24314222
TI  - [Efficacy and safety of rh-endostatin combined with docetaxel in second-line or
      intolerant toxicity for first-line treatment in patients with advanced non-small
      cell lung cancer].
AB  - OBJECTIVE: To analyze the efficacy and safety of combination of rh-endostatin
      (Endostar) with docetaxel treatment on patients of non-small cell lung cancer
      (NSCLC) who presented PD or intolerable toxicity in/after first-line
      chemotherapy. METHODS: A randomized, double-blind, placebo-controlled and multi
      center clinical trial was conducted. Patients with stage IIIB/IV of NSCLC
      experienced previous chemotherapy of one-regimen were screened for this trial. A
      total of 68 cases were included in this study. Single docetaxel and that combined
      with endostar were conducted in two arms. The response, time to progression (TTP)
      and adverse effects were observed in both arms. RESULTS: The objective response
      rate (ORR) and clinical benefit rate (CBR) were 0 and 62.5% in the combined arm,
      along with 0 and 53.3% in the single docetaxel arm, with a non-significant
      difference between the two groups (all P > 0.05), respectively. The median TTPs
      in the combined and single docetaxel arms were 2.63 and 2.07 months, respectively
      (P = 0.079). The median TTPs of the participants with progressive disease (PD)
      after first-line chemotherapy were 1.33 and 1.67 months in the combined and
      single docetaxel arms, respectively (P = 0.946). The median TTPs of the
      participants with intolerant adverse effects in first-line chemotherapy were 4.70
      months and 3.17 months in the combined and single docetaxel arms, respectively (P
      = 0.070). The median TTPs of the patients with SD after 2 therapeutic cycles in
      the combined and single docetaxel arms were 6.23 months and 3.27 months,
      respectively (P = 0.040). The differences between two arms were non-significant
      in adverse, serious adverse and cardiovascular adverse effects (all P > 0.05).
      CONCLUSIONS: Endostar may prolong TTP in patients with advanced NSCLC benefited
      from docetaxel treatment without increased toxicities.

PMID- 24314223
TI  - [Evaluation of induction chemotherapy with vinorelbine plus cisplatin (NP) or
      docetaxel plus cisplatin (TP) combined with concurrent chemoradiotherapy for
      patients with locally advanced nasopharyngeal carcinoma].
AB  - OBJECTIVE: To compare the efficacy and side effects of induction chemotherapy
      with vinorelbine plus cisplatin (NP) or docetaxel plus cisplatin (TP) combined
      with concurrent chemoradiotherapy in treating locally advanced nasopharyngeal
      carcinoma (NPC). METHODS: From January 2005 to December 2009, 146 patients with
      locally advanced nasopharyngeal carcinoma treated in our department were
      randomized into NP group (76 patients) or TP group (70 patients). Both groups
      received two cycles of induction chemotherapy and concurrent chemoradiotherapy.
      After three weeks of induction chemotherapy, the patients received concurrent
      chemoradiotherapy. The chemotherapy was recycled every three weeks. Two groups
      were treated with intensity-modulated radiation therapy. RESULTS: The short-term
      efficacy of NP group was similar to that of TP group. The 3-year overall survival
      rates, disease-free-survival rates, locoregional relapse-free survival rates and
      distant metastasis-free survival rates in the NP and TP groups were 84.2% and
      82.9%, 71.1% and 74.3%, 89.5% and 91.4%, 81.6% and 77.1%, respectively (P >
      0.05). The occurrence rates of leucopenia, anemia and acute mucositis were
      significantly higher in the TP group than those in the NP group (P < 0.05). The
      gastrointestinal toxicity, dermatitis and liver toxicity were similar in the two
      groups. CONCLUSIONS: The efficacy of NP regimen induction chemotherapy plus
      concurrent chemordiotherapy for advanced NPC is similar to that of TP regimen.
      The toxicity of the NP regimen is lower than that of NP regimen, tolerable, and
      with a good compliance.

PMID- 24314224
TI  - [Interventional therapy for lung cancer patients with superior vena cava
      syndrome].
AB  - OBJECTIVE: To investigate the method, therapeutic effect and safety of
      interventional therapy for lung cancer patients with superior vena cava syndrome
      (SVCS). METHODS: Fifty-two cases of lung cancer with SVCS who received
      interventional therapy in our hospital between Jan to Dec 2011 were included in
      this study. Of the 52 cases, 50 cases had successfully carried out superior vena
      cava stent implantation. The distal venous pressure was measured before and after
      angioplasty, and the results were assessed by Wilcoxon matched-pairs test. In
      addition, the 50 patients were followed up and the therapeutic effect and
      postoperative survival rate were evaluated. RESULTS: The mean distal venous
      pressure in the 50 patients was significantly decreased from preoperative (28.2
      +/- 1.9)cm H2O to postoperative (8.7 +/- 0.5)cm H2O (P = 0.0085). The efficacy of
      the treatment was as follows: complete remission (20/52, 38.5%), partial
      remission (28/52, 53.8%), ineffective 4 (4/52, 7.7%), and total effective rate
      92.3%. The complications after angioplasty and stent implantation included chest
      pain (12 cases, 23.1%), hematoma at the puncture site (5 cases, 9.6%), and fever
      (2 cases, 3.8%). No serious complications such as massive hemorrhage, pulmonary
      embolism and stent migration into the cardiac atrium were observed. The rate of
      postoperative restenosis was low (2/52, 3.8%). For the SCLC group, the objective
      effective rate was 74.1% and 1-year survival rate was 21.0%. For the NSCLC group,
      the objective effective rate was 21.7% and 1-year survival rate was 35.0%.
      CONCLUSIONS: For lung cancer patients with SVCS, interventional therapy may
      relief obstruction effectively, promote blood flow recovery, and relieve clinical
      symptoms. Interventional therapy with endovascular angioplasty and stenting may
      be highly recommended as the first choice for palliative treatment of SVCS. It is
      an effective initial palliative treatment. However, subsequent comprehensive anti
      tumor treatment is necessary.

PMID- 24314225
TI  - [Association between urinary cadmium and clinicopathological characteristics of
      breast cancer].
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      urinary cadmium and clinicopathological characteristics of breast cancer.
      METHODS: The clinicopathological characteristics of 240 patients with breast
      cancer were obtained and urine specimens were collected from October 2009 to July
      2010. The concentration of urinary cadmium was determined by inductively coupled
      plasma mass spectrometry (ICP-MS). chi(2) test and Wilcoxon rank sum test were
      used to analyze whether urinary cadmium is associated with clinicopathological
      characteristics of breast cancer. RESULTS: The median concentration of urine
      cadmium of 240 patients was 1.99 ug/g (25th percentile, 1.32 ug/g; 75th
      percentile, 2.88 ug/g). HER-2 positive rate, regional/distant metastasis rate,
      and advanced stage rate in patients with the highest tertile of cadmium
      concentration were significantly higher than those in the patients with second
      and lowest Cd tertiles (P = 0.042, P = 0.028 and P = 0.017, respectively), and
      28.2% vs. 16.5% for HER-2 and 47.2% vs. 32.0% for regional/distant metastasis,
      respectively. There were still significant associations between urinary cadmium
      levels and these clinicopathological parameters after being adjusted in age by
      unconditional logistic regression model, respectively (P < 0.05). CONCLUSIONS:
      The results of this study suggest that urinary cadmium levels are associated with
      the HER-2 status, regional/distant metastasis status and stages of breast cancer,
      respectively. Cadmium may induce highly aggressive breast cancer in humans.

PMID- 24314226
TI  - [Present status of clinical trials of neoadjuvant chemotherapy for gastric cancer
      and key points in their design].

PMID- 24314227
TI  - Accurate detection of subclonal single nucleotide variants in whole genome
      amplified and pooled cancer samples using HaloPlex target enrichment.
AB  - BACKGROUND: Target enrichment and resequencing is a widely used approach for
      identification of cancer genes and genetic variants associated with diseases.
      Although cost effective compared to whole genome sequencing, analysis of many
      samples constitutes a significant cost, which could be reduced by pooling samples
      before capture. Another limitation to the number of cancer samples that can be
      analyzed is often the amount of available tumor DNA. We evaluated the performance
      of whole genome amplified DNA and the power to detect subclonal somatic single
      nucleotide variants in non-indexed pools of cancer samples using the HaloPlex
      technology for target enrichment and next generation sequencing. RESULTS: We
      captured a set of 1528 putative somatic single nucleotide variants and germline
      SNPs, which were identified by whole genome sequencing, with the HaloPlex
      technology and sequenced to a depth of 792-1752. We found that the allele
      fractions of the analyzed variants are well preserved during whole genome
      amplification and that capture specificity or variant calling is not affected. We
      detected a large majority of the known single nucleotide variants present
      uniquely in one sample with allele fractions as low as 0.1 in non-indexed pools
      of up to ten samples. We also identified and experimentally validated six novel
      variants in the samples included in the pools. CONCLUSION: Our work demonstrates
      that whole genome amplified DNA can be used for target enrichment equally well as
      genomic DNA and that accurate variant detection is possible in non-indexed pools
      of cancer samples. These findings show that analysis of a large number of samples
      is feasible at low cost, even when only small amounts of DNA is available, and
      thereby significantly increases the chances of indentifying recurrent mutations
      in cancer samples.

PMID- 24314228
TI  - Neuromodulation attenuates bladder hyperactivity in a rat cystitis model.
AB  - BACKGROUND: We investigated the regulation of urinary bladder function by
      electrical stimulation of the L6 spinal nerve (SN) using cystometry in normal
      rats and in rats with cystitis induced by intravesical infusion of dilute acetic
      acid. METHODS: In anesthetized rats, a cannula was placed into the bladder dome
      for saline/acetic acid infusion and intravesical pressure monitoring. Threshold
      pressure (TP), basal pressure (BP) and inter-contraction interval (ICI) were
      measured from the bladder pressure recording and void volume (VV) was measured by
      weighing the voided fluid. RESULTS: Comparison of cystometrograms obtained with
      infusion of saline or acetic acid showed that acetic acid decreases TP, ICI and
      VV. These excitatory effects, characteristic of acetic acid induced bladder
      hyperactivity, were significantly reversed by bilateral SN stimulation (P <0.05,
      vs pre-stimulation, Student t-test). In saline perfused rats, one hour of
      bilateral SN stimulation at 10 Hz and at motor threshold (0.19 +/- 0.01
      milliamps) increased ICI (265%) and VV (217%). In rats perfused with acetic acid,
      the corresponding increases produced by SN stimulation were 350% for ICI and 383%
      for VV. The percentage increases in the acetic acid-treated group were not
      significantly higher than those in saline-treated group. CONCLUSIONS: Using
      continuous flow cystyometry, we find that SN stimulation can produce effects on
      micturition consistent with its effects on isovolumetric model, and consistent
      with the therapeutic effect observed with InterStim(r) therapy in overactive
      bladder patients. Although the effect of SN stimulation was slightly greater in
      bladder irritated over normal rats, the difference was not statistically
      significant.

PMID- 24314229
TI  - Improving amphetamine therapeutic selectivity: N,N-dimethyl-MTA has dopaminergic
      effects and does not produce aortic contraction.
AB  - Amphetamine derivatives have therapeutic potential in diseases such as attention
      deficit hyperactivity disorder, narcolepsy and obesity. However, their prolonged
      use has been associated with cardiovascular toxicity and addiction. In recent
      years, we have studied the pharmacological effects of amphetamine derivatives
      such as methylthioamphetamine (MTA) and N,N-dimethyl-thioamphetamine, with the
      aim of improving their therapeutic selectivity. In this work, we show that
      similarly to MTA, N,N-dimethyl-thioamphetamine has effects on the dopamine
      system, producing a significant increase in extracellular levels of dopamine (as
      measured by in vivo brain microdialysis) and locomotor activity, which is a
      behavioural measure of dopaminergic activation. However, unlike MTA, N,N-dimethyl
      thioamphetamine does not produce aortic contraction in vitro. Our results show
      that N,N-dimethyl-thioamphetamine is a drug that retains the dopaminergic effects
      of amphetamine derivatives but exhibits a lower potential for producing
      cardiovascular side effects. 

PMID- 24314230
TI  - Postprandial changes of lipoprotein profile: effect of abdominal obesity.
AB  - BACKGROUND: Majority of studies that focused on the influence of abdominal
      obesity on lipoprotein profile, were conducted in the fasting conditions. The
      effects of visceral fat accumulation on postprandial lipoprotein concentrations
      have not yet been studied in details. We therefore focused on the postprandial
      lipoprotein profile in otherwise healthy men and women with abdominal obesity and
      their comparison with the control group of volunteers with normal waist
      circumference. The concentration of lipoprotein classes and subclasses was
      measured before and 4 hours after a standard meal by linear polyacrylamide gel
      electrophoresis. RESULTS: A statistically significant postprandial rise in
      triacylglycerol concentration occurred in all subjects. VLDL increased 4 hours
      after meal in all subjects except the women with normal waist circumference. The
      concentration of large IDL particles increased in both non-obese men and women.
      In women with abdominal obesity, however, it decreased, while in obese men there
      was no statistically significant change. The concentration of small and medium
      sized IDL particles decreased in all volunteers. Analyzing subclasses changes of
      large, medium-sized and small LDL particles we saw no significant shift in their
      concentrations except the subclass of large LDL particles, which decreased in
      men. Concentrations of medium and small HDL particles decreased postprandially in
      all volunteers with normal waist circumference. However, they remained unchanged
      in subjects with abdominal obesity. CONCLUSIONS: We observed significant
      postprandial changes of the lipoprotein profile, but the nature and extent of
      these changes depended on gender and presence of abdominal obesity.

PMID- 24314231
TI  - Animal models of fibromyalgia.
AB  - Animal models of disease states are valuable tools for developing new treatments
      and investigating underlying mechanisms. They should mimic the symptoms and
      pathology of the disease and importantly be predictive of effective treatments.
      Fibromyalgia is characterized by chronic widespread pain with associated co
      morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction.
      In this review, we present different animal models that mimic the signs and
      symptoms of fibromyalgia. These models are induced by a wide variety of methods
      that include repeated muscle insults, depletion of biogenic amines, and stress.
      All potential models produce widespread and long-lasting hyperalgesia without
      overt peripheral tissue damage and thus mimic the clinical presentation of
      fibromyalgia. We describe the methods for induction of the model,
      pathophysiological mechanisms for each model, and treatment profiles.

PMID- 24314232
TI  - Estimation of gestational age in early pregnancy from crown-rump length when
      gestational age range is truncated: the case study of the INTERGROWTH-21st
      Project.
AB  - BACKGROUND: Fetal ultrasound scanning is considered vital for routine antenatal
      care with first trimester scans recommended for accurate estimation of
      gestational age (GA). A reliable estimate of gestational age is key information
      underpinning clinical care and allows estimation of expected date of delivery.
      Fetal crown-rump length (CRL) is recommended over last menstrual period for
      estimating GA when measured in early pregnancy i.e. 9+0-13+6 weeks. METHODS: The
      INTERGROWTH-21st Project is the largest prospective study to collect data on CRL
      in geographically diverse populations and with a high level of quality control
      measures in place. We aim to develop a new gestational age estimation equation
      based on the crown-rump length (CRL) from women recruited between 9+0-13+6 weeks.
      The main statistical challenge is modelling data when the outcome variable (GA)
      is truncated at both ends, i.e. at 9 and 14 weeks.We explored three alternative
      statistical approaches to overcome the truncation of GA. To evaluate these
      strategies we generated a data set with no truncation of GA that was similar to
      the INTERGROWTH-21st Project CRL data, which we used to explore the performance
      of different methods of analysis of these data when we imposed truncation at 9
      and 14 weeks of gestation. These 3 methods were first tested in a simulation
      based study using a previously published dating equation by Verburg et al. and
      evaluated how well each of them performed in relation to the model from which the
      data were generated. After evaluating the 3 approaches using simulated data based
      on the Verburg equations, the best approach will be applied to the INTERGROWTH
      21st Project data to estimate GA from CRL. RESULTS: Results of these rather "ad
      hoc" statistical methods correspond very closely to the "real data" for Verburg,
      a data set that is similar to the INTERGROWTH-21st project CRL data set.
      CONCLUSIONS: We are confident that we can use these approaches to get reliable
      estimates based on INTERGROWTH-21st Project CRL data. These approaches may be a
      solution to other truncation problems involving similar data though their
      application to other settings would need to be evaluated.

PMID- 24314233
TI  - Safety aspects in surgical treatment of pathological fractures of the proximal
      femur - modular endoprosthetic replacement vs. intramedullary nailing.
AB  - BACKGROUND: Pathologic fractures of the femoral intertrochanteric and
      subtrochanteric region require special consideration in terms of biomechanically
      stable fixation and durability of the implant. In addition, the type of surgery
      might also influence patient survival. We conducted this retrospective study to
      evaluate the safety of modular proximal femur replacement compared to
      intramedullary nailing with patient survival being the primary and complications
      the secondary endpoint. METHODS: We retrospectively studied the records of 20
      consecutive patients with actual pathologic fracture due to bone metastasis in
      the intertrochanteric and subtrochanteric part of the femur. The pathologic
      fractures were stabilized with a locked cephalomedullary nail in 12 patients and
      treated with en-bloc resection and modular proximal femur replacement in eight
      patients. RESULTS: In the tumor prosthesis group median patient survival was more
      than twice as high (4.5 months, IQR 2.3 - 16.5) than in the osteosynthesis group
      (2.0 months, IQR 0.3 - 20.5), but did not reach significance (p = 0.58). Besides,
      a significantly better preoperative general health status in patients with
      endoprosthetic reconstruction puts better survival into perspective. Median
      implant survivorship did not differ between groups with 2.5 (IQR 1.0 - 7.5)
      months for endoprothesis and 3.0 (IQR 0.3 - 11.0) months for osteosynthesis (p =
      0.93). Complication rates were comparable with 25% in each group. CONCLUSION:
      Patient survival was not influenced by type of surgery or choice of implant.
      Preoperative general health condition and ambulatory capacity may aid in decision
      for type of surgery and improve patient safety, respectively.

PMID- 24314234
TI  - Bacterial diversity in the indoor air of pharmaceutical environment.
AB  - AIMS: To monitor bacterial diversity of ISO Class 8 pharmaceutical clean room
      environment using conventional culture-based methods and pyrosequencing analysis.
      METHODS AND RESULTS: Bacterial isolates were obtained through viable particulate
      air monitoring, passive air monitoring and surface-monitoring procedures. A total
      of 157 bacterial isolates were obtained and assigned to four different phyla,
      Actinobacteria, Firmicutes, Proteobacteria and Deinococcus-Thermus, encompassing
      52 species of 24 genera based on 16S rRNA gene sequence analysis. The genera
      Micrococcus and Staphylococcus were found as the main bacterial groups among the
      isolates. However, a big discrepancy was found between the culture based and
      pyrosequencing results. A total of 11 409 quality reads were obtained from the
      pyrosequencing analysis, and the subsequent phylogenetic analysis indicated that
      Proteobacteria was the most abundant group at phylum level, followed by
      Actinobacteria and Firmicutes. Bacillus, Propionibacterium and Acinetobacter were
      identified as the most abundant genera by the pyrosequencing analysis.
      CONCLUSIONS: The culture-based results were in line with previous reports on the
      airborne bacterial composition of various environments, but the pyrosequencing
      analysis revealed a unique diversity of bacteria in this case. No significant
      pathogens above Riskgroup 2 were found from either culture based or
      pyrosequencing studies. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of
      various bacterial taxa including a number of groups, whose presence in air is
      previously unknown, was confirmed through this analysis. The main source of
      bacteria in the indoor air environment of pharmaceutical processes is likely
      human, but no significant primary pathogens were detected. Culture-based analysis
      may give limited information on the bacterial diversity of air environment.

PMID- 24314235
TI  - Primary tumor versus metastasis: new experimental models for studies on cancer
      cell homing and metastasis in melanoma.

PMID- 24314236
TI  - Relationship between cardiac function and resting cerebral blood flow: MRI
      measurements in healthy elderly subjects.
AB  - Although both impaired cardiac function and reduced cerebral blood flow are
      associated with ageing, current knowledge of the influence of cardiac function on
      resting cerebral blood flow (CBF) is limited. The aim of this study was to
      investigate the potential effects of cardiac function on CBF. CBF and cardiac
      output were measured in 31 healthy subjects 50-75 years old using magnetic
      resonance imaging techniques. Mean values of CBF, cardiac output and cardiac
      index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2),
      respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l
      min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac
      index on CBF or structural signs of brain ageing were observed. However,
      fractional brain flow defined as the ratio of total brain flow to cardiac output
      was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and
      furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003).
      Fractional brain flow was also inversely correlated with cerebral white matter
      lesion grade, although this effect was not significant when adjusted for age.
      Frequency analysis of heart rate variability showed a gender-related inverse
      association of increased low-to-high-frequency power ratio with CBF and
      fractional brain flow. The findings do not support a direct effect of cardiac
      function on CBF, but demonstrates gender-related differences in cardiac output
      distribution. We propose fractional brain flow as a novel index that may be a
      useful marker of adequate brain perfusion in the context of ageing as well as
      cardiovascular disease.

PMID- 24314237
TI  - Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to
      determine in utero fetal hypoxic status.
AB  - BACKGROUND: Hypoxia in utero can lead to stillbirth and severe perinatal injury.
      While current prenatal tests can identify fetuses that are hypoxic, none can
      determine the severity of hypoxia/acidemia. We hypothesized a hypoxic/acidemic
      fetus would up-regulate and release hypoxia-induced mRNA from the fetoplacental
      unit into the maternal circulation, where they can be sampled and quantified.
      Furthermore, we hypothesized the abundance of hypoxia induced mRNA in the
      maternal circulation would correlate with severity of fetal hypoxia/acidemia in
      utero. We therefore examined whether abundance of hypoxia-induced mRNA in the
      maternal circulation correlates with the degree of fetal hypoxia in utero.
      METHODS: We performed a prospective study of two cohorts: 1) longitudinal study
      of pregnant women undergoing an induction of labor (labor induces acute fetal
      hypoxia) and 2) pregnancies complicated by severe preterm growth restriction
      (chronic fetal hypoxia). For each cohort, we correlated hypoxia induced mRNA in
      the maternal blood with degree of fetal hypoxia during its final moments in
      utero, evidenced by umbilical artery pH or lactate levels obtained at birth.
      Gestational tissues and maternal bloods were sampled and mRNAs quantified by
      microarray and RT-PCR. RESULTS: Hypoxia-induced mRNAs in maternal blood rose
      across labor, an event that induces acute fetal hypoxia. They exhibited a
      precipitous increase across the second stage of labor, a particularly hypoxic
      event. Importantly, a hypoxia gene score (sum of the relative expression of four
      hypoxia-induced genes) strongly correlated with fetal acidemia at birth. Hypoxia
      induced mRNAs were also increased in the blood of women carrying severely growth
      restricted preterm fetuses, a condition of chronic fetal hypoxia. The hypoxia
      gene score correlated with the severity of ultrasound Doppler velocimetry
      abnormalities in fetal vessels. Importantly, the hypoxia gene score (derived from
      mRNA abundance in maternal blood) was significantly correlated with the degree of
      fetal acidemia at birth in this growth restriction cohort. CONCLUSIONS: Abundance
      of mRNAs coding hypoxia-induced genes circulating in maternal blood strongly
      correlates with degree of fetal hypoxia/acidemia. Measuring hypoxia-induced mRNA
      in maternal blood may form the basis of a novel non-invasive test to clinically
      determine the degree of fetal hypoxia/acidemia while in utero.

PMID- 24314239
TI  - Identification of a putative germ plasm in the amphipod Parhyale hawaiensis.
AB  - BACKGROUND: Specification of the germ line is an essential event during the
      embryonic development of sexually reproducing animals, as germ line cells are
      uniquely capable of giving rise to the next generation. Animal germ cells arise
      through either inheritance of a specialized, maternally supplied cytoplasm called
      'germ plasm' or though inductive signaling by somatic cells. Our understanding of
      germ cell determination is based largely on a small number of model organisms. To
      better understand the evolution of germ cell specification, we are investigating
      this process in the amphipod crustacean Parhyale hawaiensis. Experimental
      evidence from previous studies demonstrated that Parhyale germ cells are
      specified through inheritance of a maternally supplied cytoplasmic determinant;
      however, this determinant has not been identified. RESULTS: Here we show that the
      one-cell stage Parhyale embryo has a distinct cytoplasmic region that can be
      identified by morphology as well as the localization of germ line-associated
      RNAs. Removal of this cytoplasmic region results in a loss of embryonic germ
      cells, supporting the hypothesis that it is required for specification of the
      germ line. Surprisingly, we found that removal of this distinct cytoplasm also
      results in aberrant somatic cell behaviors, as embryos fail to gastrulate.
      CONCLUSIONS: Parhyale hawaiensis embryos have a specialized cytoplasm that is
      required for specification of the germ line. Our data provide the first
      functional evidence of a putative germ plasm in a crustacean and provide the
      basis for comparative functional analysis of germ plasm formation within non
      insect arthropods.

PMID- 24314238
TI  - The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3
      dependent necroptosis.
AB  - BACKGROUND: Osteosarcoma is the most frequent primary malignant bone tumor,
      notorious for its lung metastasis. Shikonin, an effective constituent extracted
      from Chinese medicinal herb, was demonstrated to induce necroptosis in some
      cancers. METHODS: MTT assay was performed to detect cell survival rate in vitro.
      Flow cytometry was used to analyze cell cycle and cell death. Western blot was
      performed to determine the expression levels of RIP1, RIP3, caspase-3, caspase-6
      and PARP. The tibial primary and lung metastatic osteosarcoma models were used to
      evaluate the anti-tumor effect of shikonin in vivo. RESULTS: The cell survival
      rate was decreased in a dose and time dependent manner when treated with
      shikonin. No major change in cell cycle was observed after shikonin treatment.
      The cell death induced by shikonin could be mostly rescued by specific
      necroptosis inhibitor necrostatin-1, but not by general caspase inhibitor Z-VAD
      FMK. The number of necrotic cells caused by shikonin was decreased after being
      pretreated with Nec-1 detected by flow cytometry in K7 cells. After 8-hour
      treatment of shikonin, the expression levels of RIP1 and RIP3 were increased
      while caspase-3, caspase-6 and PARP were not activated in K7 and U2OS cells
      determined by Western blot. Size of primary tumor and lung metastasis in shikonin
      treated group were significantly reduced. The protein levels of RIP1 and RIP3 in
      primary tumor tissues were increased by shikonin. The overall survival of lung
      metastatic models was longer compared with control group (p < 0.001).
      CONCLUSIONS: Shikonin had prompt but profound anti-tumor effect on both primary
      and metastatic osteosarcoma, probably by inducing RIP1 and RIP3 dependent
      necroptosis. Shikonin would be a potential anti-tumor agent on the treatment of
      primary and metastatic osteosarcoma.

PMID- 24314240
TI  - [Update knowledge about the classification of lymphomas].

PMID- 24314241
TI  - [Anaplastic large cell lymphoma: an array-based comparative genomic hybridization
      study].
AB  - OBJECTIVE: To use array-based comparative genomic hybridization (aCGH) technology
      to study the molecular cytogenetic abnormalities of anaplastic large cell
      lymphoma (ALCL) at genome level. METHODS: ALK protein expression and molecular
      genetic abnormalities were detected by immunohistochemistry and fluorescence in
      situ hybridization, respectively, in 25 cases of ALCL. Any chromosomal
      gains/losses were detected by aCGH and correlated with ALK status. RESULTS: aCGH
      showed that chromosomal alterations in all 25 ALCL cases, and the frequency of
      chromosomal gains was higher than that of the losses. Chromosomal gains at
      5p13.2, 3q21.1, 2q21.3, 3p25.1, 14q32.33, and 17q21.2 regions were detected in
      more than 50% of the ALCL cases; gains at 4q27, 6p22.1, 20p11.21, 2q22.3, 4q35.1,
      1p36.22, 8p23.1, 8p12, 11q14.1, 12q13.13, and 19p13.3 regions were detected in
      30%-50% of the ALCL cases; chromosomal losses at 3q26.1 and 3q26.31 regions were
      detected in 36.0% (9/25) and 24.0% (6/25) of the ALCL cases, respectively.
      Chromosomal gains at 2q21.3, 6p22.1 and 3p25.1 regions showed significant
      differences between ALK (+) and ALK (-) ALCL groups (P < 0.05). CONCLUSIONS: aCGH
      demonstrates complex molecular genetic variations in all ALCL cases. Gains at
      2q21.3, 6p22.1 and 3p25.1 regions are significantly different between ALK (+) and
      ALK (-) ALCL groups, suggesting that the pathogenesis of ALK (+) and ALK (-) ALCL
      may involve different signaling pathway.

PMID- 24314242
TI  - [B-cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations].
AB  - OBJECTIVE: To identify and investigate clinicopathological features of B cell
      lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations ("double-hit"
      lymphoma). METHODS: Tissue microarray was constructed from formalin-fixed and
      paraffin-embedded tissue samples of aggressive B cell lymphomas diagnosed between
      2009 and 2012, including 129 cases of diffuse large B cell lymphoma (DLBCL), 5
      cases of B-cell lymphoma, unclassifiable with features intermediate between
      diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU), 7 cases of Burkitt
      lymphoma and 4 cases of high-grade follicular lymphoma with diffuse large B cell
      lymphoma component. Interphase fluorescence in-situ hybridization (FISH) was
      performed with a panel of probes including myc, bcl-2/IgH and bcl-6 to document
      related gene translocation and copy number changes. Medical record review was
      performed and follow-up data was recorded. RESULTS: Among 145 cases, 5 cases
      (3.4%) of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6
      rearrangements (double-hit lymphomas) were identified, including 2 cases
      involving myc and bcl-2 translocations (1 DLBCL and 1 BCLU), and 3 cases
      involving myc and bcl-6 translocations (all DLBCLs). Three cases with concurrent
      bcl-2/IgH and bcl-6 translocations were found. Single gene translocations or
      increase of copy numbers were found in 66 cases, representing 51.2% (66/129) of
      all de novo DLBCLs. Ki-67 index of the 5 "double-hit" lymphomas ranged from 60%
      to 100%. Clinical follow-up data were available in 4 of the 5 "double-hit"
      lymphoma patients, three of whom died within 2 years and 1 patient was alive
      after 36 months of follow-up. CONCLUSIONS: "Double-hit" B-cell lymphomas are rare
      and can only be identified by molecular detection. They should not be considered
      synonymous with BCLU morphologically, and may present entities within other
      morphological spectra. Most of the patients have a poor prognosis. Further in
      depth studies of larger case numbers are required to determine the pathologic and
      genetic variables of the lesion.

PMID- 24314243
TI  - [Diffuse large B-cell lymphoma of testis: a clinicopathologic and
      immunophenotypic study of 58 cases].
AB  - OBJECTIVE: To investigate the clinicopathologic features, immunophenotype,
      diagnosis and differential diagnosis, and prognostic factors of testicular
      diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical and pathologic
      profiles of 58 cases of testicular DLBCL were investigated.Immunohistochemical
      stainings and EBER1/2 in situ hybridization were performed on formalin fixed
      tissues. RESULTS: The average age of the patients was 62.1 years, and the median
      age was 65 years. The course of disease was short in most of the cases. Clinical
      stages at diagnosis were mainly stage I or II (87.9%, 51/58). Forty eight
      patients (82.8%) had unilateral testis involvement. Inguinal lymphadenopathy was
      observed in 12 (20.7%) patients and the other organs were seldom involved.
      Morphologically, centroblast-like neoplastic cells infiltrated interstitial
      tissue of testis diffusely and invaded into seminiferous tubules. Tunica
      albuginea and vessels were involved in 14 (24.1%) and 10 (17.2%) patients,
      respectively. Immunophenotype analysis showed predominant non-GCB type of DLBCL
      (48/58, 82.8%) by Hans classification. No EBV infection was detected. Follow-up
      data were available in 48 (82.8%) patients. Twenty eight patients (58.3%) died of
      the disease. One-year, 3-year, and 5-year overall survivals were 55.7%, 31.6% and
      27.6%, respectively. Age (older than 60 years), B-symptoms, high serum level of
      LDH, advanced Ann Arbor stage as well as lack of combination of therapy were
      associated with a poor prognosis. CONCLUSIONS: This large series of testicular
      DLBCL mainly present with local disease at diagnosis. Most cases show non-GCB
      immunophenotype. Despite early clinical stage at presentation, the prognosis is
      poor. Combined chemotherapy postoperation may prolong survival of the patients.

PMID- 24314244
TI  - [Epithelioid hemangioma: a clinicopathologic analysis of 7 cases].
AB  - OBJECTIVE: To study the clinicopathologic features, diagnosis and differential
      diagnosis of epithelioid hemangioma. METHODS: The morphologic features of 7 cases
      of epithelioid hemangioma of skin, bone and venous vessels were studied. RESULTS:
      There were altogether 4 male and 3 female patients (median age = 34 years; age
      range from 14 to 54 years). The 3 skin cases presented as single or multiple
      erythematous to bluish nodules or papules, with or without itchiness. The 2 bone
      cases appeared as osteolytic expansile lesions on radiologic examination. The
      remaining 2 cases involved medium-sized venous structures and presented as small
      isolated nodules in soft tissue. Histologically, the lesions were characterized
      by the presence of exuberant endothelial proliferations with various degree of
      inflammatory reaction. The neoplastic endothelial cells were plump, eosinophilic
      and polygonal, forming vascular channels. Occasional solid sheet-like arrangement
      was demonstrated. Intracytoplasmic vacuoles were commonly identified, indicating
      formation of primary lumen. The surrounding stroma contained various number of
      eosinophils and lymphoplasmacytic cells. Immunohistochemical study showed that
      the tumor cells were positive for endothelial markers (CD31 and CD34) and
      negative for epithelial marker (cytokeratin). Follow-up information was available
      in 6 cases. The duration of follow-up ranged from 5 to 36 months (median = 14
      months). There was no evidence of recurrence or distant metastasis. CONCLUSIONS:
      Epithelioid hemangioma is a rare benign curable lesion which can be multifocal,
      involving skin, soft tissue and bone. It needs to be distinguished from Kimura's
      disease and epithelioid hemangioendothelioma.

PMID- 24314245
TI  - [Invasive lobular carcinoma of basal-like subtype of breast: a clinicopathologic
      analysis].
AB  - OBJECTIVE: To investigate the clinicopathologic features, clinical progress and
      prognosis of the basal-like subtype of invasive lobular carcinoma (ILC) of the
      breast. METHODS: Four cases of ILC were analyzed by detailed histopathologic
      observation and immunohistochemical staining for E-cadherin, p120 catenin, ER,
      PR, HER2, CK5/6, EGFR, p63, p53, Ki-67 using MaxVision method. The follow-up and
      clinical data were analyzed. RESULTS: Morphologically, one case was mixed ILC and
      three cases were pleomorphic ILC. The tumor cells were negative for E-cadherin
      except one case with focal membrane positivity, and all showed p120 catenin
      cytoplasmic positivity except one case with focal membrane positivity. All cases
      were negative for ER, PR and HER2 (triple negative), and positive for EGFR and
      CK5/6. Two cases were positive for p63. The cases were partly and weakly positive
      for p53, and the Ki-67 positive rate was between 30% and 75%. Follow-up data
      showed that two cases developed chest wall metastases, and in one case, there was
      progression to liver and abdominal metastases. CONCLUSIONS: ILC of the breast are
      ER, PR and HER2 "triple negative", CK5/6 and EGFR positive, indicative of basal
      like characteristics. Basal-like subtype of ILC are peculiarly prone to
      metastasis and poor response to chemotherapy, suggesting that it is associated
      with poor prognosis.

PMID- 24314247
TI  - [Value of computer-assisted slide-screening system in ThinPrep cervical
      cytology].
AB  - OBJECTIVE: To investigate the value of computer-assisted slide-screening system
      (ThinPrep imaging system, TIS) in the diagnosis of cervical Thinprep smears.
      METHODS: A total of 19 600 ThinPrep smears were collected, including 9800 slides
      by TIS-assisted screening from September 2011 to March 2012 and 9800 slides by
      manual screening from September 2010 to April 2011 as control. The detection
      rates of abnormal cells and common microbial infection by the different screening
      methods were compared. With histopathological diagnosis of colposcopic biopsy as
      the gold standard, the screening efficiency and correlation of cytologic
      diagnosis among different screening methods were analyzed. RESULTS: Compared with
      manual screening, the detection rate of abnormal cells in 9800 cases by TIS
      assisted screen was increased from 5.4% (525/9800) to 6.8% (665/9800), mainly in
      the categories of ASCUS and LSIL (P < 0.05). TIS had a higher accordance rate
      between cytologic diagnosis and histopathological diagnosis in the NILM and ASCUS
      than that by manual screening. False-negative rate of finding abnormal cells by
      TIS decreased from 8.5% (17/200) to 0.7% (2/289, P < 0.01) with an increased
      sensitivity compared to manual screening, although the specificity was similar.
      Both TIS and manual screening had advantages and disadvantages respectively in
      the detection of microbial organisms. TIS improved screening efficiency by 50%.
      CONCLUSION: TIS improves not only the screening efficiency but also the detection
      of abnormal cells with a reduced false negativity, and it therefore has a broad
      application prospect.

PMID- 24314246
TI  - [Morphology and microRNA expression profiles of drug-resistant cells in
      hepatocellular carcinoma].
AB  - OBJECTIVE: To compare morphological differences of three drug-resistant
      hepatocellular carcinoma (HCC) cell subclones (Huh-7/ADM, Huh-7/CBP, Huh-7/MMC)
      and their parental Huh-7 cell line, to analyze differential microRNA (miRNA)
      expression profiles in these cells and, finally to screen for the abnormal
      expressed miRNAs in drug-resistant HCC cells. METHODS: Cellular morphology was
      observed by histology and transmission electron microscopy. MiRNA microarray was
      used to analyze the differential miRNA expression profiles in these cells (Huh-7,
      Huh-7/ADM, Huh-7/CBP, Huh-7/MMC) followed by real time quantitative PCR
      validation. RESULTS: The drug-resistant cells had more intracytoplasmic
      organelles and were larger in size along with increased cytological pleomorphism
      than the parental Huh-7 cells. Compared with the parental Huh-7 cells, 32
      simultaneously up-regulated and 22 down-regulated miRNAs were found in three drug
      resistant cells. Up-regulation of miR-15a, miR-16, miR-27b, miR-30b, miR-146a,
      miR-146b-5p, miR-181a, miR-181d and miR-194 was verified by RT-qPCR. CONCLUSION:
      Drug-resistant HCC cells have abnormal expressed miRNAs, which may be explored to
      further investigate the association of miRNA expressions with multidrugs
      resistance in HCC.

PMID- 24314248
TI  - [Effect of P13K/AKT signal pathway regulation on expression of XIAP and cIAP2 in
      ovarian cancer cells].

PMID- 24314249
TI  - [Application of GeneScan analysis technique in detection of T-cell receptor gene
      rearrangement in lymphoma].

PMID- 24314250
TI  - [Hodgkin's lymphoma manifested as vertebral lesions: report of two cases].

PMID- 24314251
TI  - [Tattoo pigment-related lymphadenitis: report of a case].

PMID- 24314252
TI  - [Primary cardiac embryonal rhabdomyosarcoma: report of a case].

PMID- 24314253
TI  - [Thyroid follicular carcinoma-like renal cell carcinoma: report of a case].

PMID- 24314254
TI  - [Recent advances on ovarian epithelial cancer: definition, subtypes and
      pathologic features].

PMID- 24314255
TI  - [New entities of soft tissue tumors].

PMID- 24314256
TI  - [Update on relation between follicular helper T cells and lymphoma].

PMID- 24314257
TI  - [Significance and application of c-myc in diffuse large B-cell lymphoma].

PMID- 24314258
TI  - [Cell surface carbohydrate and cancer stem cells].

PMID- 24314259
TI  - Repertoire, unified nomenclature and evolution of the Type III effector gene set
      in the Ralstonia solanacearum species complex.
AB  - BACKGROUND: Ralstonia solanacearum is a soil-borne beta-proteobacterium that
      causes bacterial wilt disease in many food crops and is a major problem for
      agriculture in intertropical regions. R. solanacearum is a heterogeneous species,
      both phenotypically and genetically, and is considered as a species complex.
      Pathogenicity of R. solanacearum relies on the Type III secretion system that
      injects Type III effector (T3E) proteins into plant cells. T3E collectively
      perturb host cell processes and modulate plant immunity to enable bacterial
      infection. RESULTS: We provide the catalogue of T3E in the R. solanacearum
      species complex, as well as candidates in newly sequenced strains. 94 T3E
      orthologous groups were defined on phylogenetic bases and ordered using a uniform
      nomenclature. This curated T3E catalog is available on a public website and a
      bioinformatic pipeline has been designed to rapidly predict T3E genes in newly
      sequenced strains. Systematical analyses were performed to detect lateral T3E
      gene transfer events and identify T3E genes under positive selection. Our
      analyses also pinpoint the RipF translocon proteins as major discriminating
      determinants among the phylogenetic lineages. CONCLUSIONS: Establishment of T3E
      repertoires in strains representatives of the R. solanacearum biodiversity
      allowed determining a set of 22 T3E present in all the strains but provided no
      clues on host specificity determinants. The definition of a standardized
      nomenclature and the optimization of predictive tools will pave the way to
      understanding how variation of these repertoires is correlated to the
      diversification of this species complex and how they contribute to the different
      strain pathotypes.

PMID- 24314260
TI  - FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis in rheumatoid arthritis.
AB  - INTRODUCTION: The FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis plays a
      fundamental role in proliferation and differentiation of dendritic cells (DCs).
      As DCs play an important role in rheumatoid arthritis (RA) immunopathology we
      studied in detail the Flt3L/CD135 axis in RA patients. METHODS: The levels of
      Flt3L in (paired) serum and synovial fluid (SF) were quantified by enzyme-link
      immunosorbent assay (ELISA). Expression of Flt3L and CD135 in paired peripheral
      blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) was
      quantified by fluorescence-activated cell sorting (FACS). The expression of
      Flt3L, CD135 and TNF-Converting Enzyme (TACE) in synovial tissues (STs) and in
      vitro polarized macrophages and monocyte-derived DCs (Mo-DCs) was assessed by
      quantitative PCR (qPCR). CD135 ST expression was evaluated by
      immunohistochemistry and TACE ST expression was assessed by immunofluorescence.
      Flt3L serum levels were assessed in RA patients treated with oral prednisolone or
      adalimumab. RESULTS: Flt3L levels in RA serum, SF and ST were significantly
      elevated compared to gout patients and healthy individuals (HI). RA SF monocytes,
      natural killer cells and DCs expressed high levels of Flt3L and CD135 compared to
      HI. RA ST CD68+ and CD163+ macrophages, CD55+ fibroblast-like synoviocytes (FLS),
      CD31+ endothelial cells or infiltrating monocytes and CD19+ B cells co-expressed
      TACE. IFN-gamma-differentiated macrophages expressed higher levels of Flt3L
      compared to other polarized macrophages. Importantly, Flt3L serum levels were
      reduced by effective therapy. CONCLUSIONS: The Flt3L/CD135 axis is active in RA
      patients and is responsive to both prednisolone and adalimumab treatment.
      Conceivably, this ligand receptor pair represents a novel therapeutic target.

PMID- 24314262
TI  - Multicolor banding remains an important adjunct to array CGH and conventional
      karyotyping.
AB  - BACKGROUND: Array comparative genomic hybridization (CGH) for high resolution
      detection of chromosome imbalance, and karyotype analysis using G-banded
      chromosomes for detection of chromosome rearrangements, provide a powerful
      diagnostic armoury for clinical cytogenetics. However, abnormalities detected by
      karyotype analysis cannot always be characterised by scrutinising the G-banded
      pattern alone, and imbalance detected by array CGH cannot always be visualised in
      the context of metaphase chromosomes. In some cases further techniques are needed
      for detailed characterisation of chromosomal abnormalities. We investigated seven
      cases involving structural chromosome rearrangements detected by karyotype
      analysis, and one case where imbalance was primarily detected by array CGH.
      Multicolor banding (MCB) was used in all cases and proved invaluable in
      understanding the detailed structure of the abnormalities. FINDINGS: Karyotype
      analysis detected structural chromosome rearrangements in 7 cases and MCB was
      used to help refine the karyotype for each case. Array CGH detected imbalance in
      an eighth case, where previously, G-banded chromosome analysis had reported a
      normal karyotype. Karyotype analysis of a second tissue type revealed this
      abnormality in mosaic form; however, MCB was needed in order to characterise this
      rearrangement. MCB provided information for the delineation of small deletions,
      duplications, insertions and inversions and helped to assign breakpoints which
      were difficult to identify from G-banded preparations due to ambiguous banding
      patterns. CONCLUSION: Despite the recent advance of array CGH in molecular
      cytogenetics we conclude that fluorescence in situ hybridization, including MCB,
      is still required for the elucidation of structural chromosome rearrangements,
      and remains an essential adjunct in modern diagnostic laboratories.

PMID- 24314261
TI  - The combination of L-4F and simvastatin stimulate cholesterol efflux and related
      proteins expressions to reduce atherosclerotic lesions in apoE knockout mice.
AB  - BACKGROUND: Both L-4F, one apolipoprotein A-1 mimetic peptide, and statins can
      reduce progression of atherosclerosis by different mechanisms. The combination of
      the two drugs can cause lesion regression by rendering HDL anti-inflammatory. We
      postulated that combination of L-4F and simvastatin may stimulate cholesterol
      efflux and related proteins expressions to alleviate atherosclerosis. METHODS:
      Thirty male wild-type (W-T) C57 BL/6 mice and apo E(-/-) mice were divided into
      five groups: W-T group, atherosclerosis (AS) group, simvastatin group, L-4F group
      and the combination of simvastatin and L-4F group. After 16 weeks, serum lipids,
      atherosclerotic lesion areas, cholesterol efflux and the expressions of related
      proteins including ABCA1, SR-BI, ABCG1, LXRalpha and PPARgamma were evaluated.
      RESULTS: The aortic atherosclerotic lesion areas were reduced more significantly
      by combination of both drugs than single agent, and cholesterol efflux was
      promoted more in combination group than simvastatin and L-4F group. Besides, the
      combination group promoted expressions of cholesterol efflux related proteins.
      CONCLUSIONS: The combination of L-4F and simvastatin reduced atherosclerotic
      lesions, which stimulates cholesterol efflux by promoting the expressions of
      related proteins. In addition, these results help us further understand that the
      regression of the atherosclerosis would be assessed by reduction in LDL-C with
      increase of cholesterol efflux.

PMID- 24314263
TI  - Unexpected earthworm effects on forest understory plants.
AB  - BACKGROUND: Introduced earthworms are widespread in forests of North America
      creating significant negative impacts on forest understory communities. However,
      much of the reported evidence for negative earthworm effects comes from field
      investigations either comparing invaded and non-invaded forests or across
      invasion fronts. While important, such work is rarely able to capture the true
      effect of earthworms on individual plant species because most forests in North
      America simultaneously face multiple stressors which may confound earthworm
      impacts.We used a mesocosm experiment to isolate effects of the anecic introduced
      earthworm, Lumbricus terrestris L. on seedlings of 14 native plant species
      representing different life form groups (perennial herb, graminoid, and tree).
      RESULTS: Earthworm presence did not affect survival, fertility or biomass of any
      of the seedling plant species tested over a 17-week period. However, L.
      terrestris presence significantly decreased growth of two sedges (Carex
      retroflexa Muhl. ex Willd. and Carex radiata (Wahlenb.) Small) by decreasing the
      number of culms. CONCLUSIONS: Our mesocosm results with seedlings contrast with
      field reports indicating extensive and significant negative effects of introduced
      earthworms on many mature native forbs, and positive effects on sedges. We
      suggest that earthworm impacts are context- and age-specific and that
      generalizations about their impacts are potentially misleading without
      considering and manipulating other associated factors.

PMID- 24314264
TI  - Restricted mean survival time: an alternative to the hazard ratio for the design
      and analysis of randomized trials with a time-to-event outcome.
AB  - BACKGROUND: Designs and analyses of clinical trials with a time-to-event outcome
      almost invariably rely on the hazard ratio to estimate the treatment effect and
      implicitly, therefore, on the proportional hazards assumption. However, the
      results of some recent trials indicate that there is no guarantee that the
      assumption will hold. Here, we describe the use of the restricted mean survival
      time as a possible alternative tool in the design and analysis of these trials.
      METHODS: The restricted mean is a measure of average survival from time 0 to a
      specified time point, and may be estimated as the area under the survival curve
      up to that point. We consider the design of such trials according to a wide range
      of possible survival distributions in the control and research arm(s). The
      distributions are conveniently defined as piecewise exponential distributions and
      can be specified through piecewise constant hazards and time-fixed or time
      dependent hazard ratios. Such designs can embody proportional or non-proportional
      hazards of the treatment effect. RESULTS: We demonstrate the use of restricted
      mean survival time and a test of the difference in restricted means as an
      alternative measure of treatment effect. We support the approach through the
      results of simulation studies and in real examples from several cancer trials. We
      illustrate the required sample size under proportional and non-proportional
      hazards, also the significance level and power of the proposed test. Values are
      compared with those from the standard approach which utilizes the logrank test.
      CONCLUSIONS: We conclude that the hazard ratio cannot be recommended as a general
      measure of the treatment effect in a randomized controlled trial, nor is it
      always appropriate when designing a trial. Restricted mean survival time may
      provide a practical way forward and deserves greater attention.

PMID- 24314265
TI  - Safety and efficacy of vemurafenib in end stage renal failure.
AB  - BACKGROUND: Serine-threonine inhibitors, such as vemurafenib, are being used
      increasingly in cancer treatment, and the toxicity and therapeutic benefit need
      to be balanced carefully both before and during treatment. CASE PRESENTATION: A
      patient with metastatic melanoma and end stage renal failure who was on
      peritoneal dialysis was treated with the serine-threonine kinase inhibitor,
      vemurafenib. After 5 months of treatment, a substantial response to vemurafenib
      was observed using imaging, but when he developed a prolonged QTc interval
      (common toxicity criteria (CTC) grade 3), treatment was interrupted. Vemurafenib
      was restarted at a reduced dose when the QTc interval returned to normal. The
      patient has had a significant response to vemurafenib and continued on treatment
      for 12 months after beginning the therapy. CONCLUSION: This is the first reported
      case of end stage renal failure in a patient who is taking vemurafenib. Although
      the patient developed QTc prolongation, it appears to be asymptomatic, and was
      managed with dose reduction. This case highlights the need for closer QTc
      monitoring at the start and during treatment.

PMID- 24314266
TI  - Antifungal activity of cinnamic acid derivatives involves inhibition of benzoate
      4-hydroxylase (CYP53).
AB  - AIMS: CYP53A15, from the sorghum pathogen Cochliobolus lunatus, is involved in
      detoxification of benzoate, a key intermediate in aromatic compound metabolism in
      fungi. Because this enzyme is unique to fungi, it is a promising drug target in
      fungal pathogens of other eukaryotes. METHODS AND RESULTS: In our work, we showed
      high antifungal activity of seven cinnamic acid derivatives against C. lunatus
      and two other fungi, Aspergillus niger and Pleurotus ostreatus. To elucidate the
      mechanism of action of cinnamic acid derivatives with the most potent antifungal
      properties, we studied the interactions between these compounds and the active
      site of C. lunatus cytochrome P450, CYP53A15. CONCLUSION: We demonstrated that
      cinnamic acid and at least four of the 42 tested derivatives inhibit CYP53A15
      enzymatic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: By identifying selected
      derivatives of cinnamic acid as possible antifungal drugs, and CYP53 family
      enzymes as their targets, we revealed a potential inhibitor-target system for
      antifungal drug development.

PMID- 24314268
TI  - Immortalized myogenic cells from congenital muscular dystrophy type1A patients
      recapitulate aberrant caspase activation in pathogenesis: a new tool for MDC1A
      research.
AB  - BACKGROUND: Congenital muscular dystrophy Type 1A (MDC1A) is a severe, recessive
      disease of childhood onset that is caused by mutations in the LAMA2 gene encoding
      laminin-alpha2. Studies with both mouse models and primary cultures of human
      MDC1A myogenic cells suggest that aberrant activation of cell death is a
      significant contributor to pathogenesis in laminin-alpha2-deficiency. METHODS: To
      overcome the limited population doublings of primary cultures, we generated
      immortalized, clonal lines of human MDC1A myogenic cells via overexpression of
      both CDK4 and the telomerase catalytic component (human telomerase reverse
      transcriptase (hTERT)). RESULTS: The immortalized MDC1A myogenic cells
      proliferated indefinitely when cultured at low density in high serum growth
      medium, but retained the capacity to form multinucleate myotubes and express
      muscle-specific proteins when switched to low serum medium. When cultured in the
      absence of laminin, myotubes formed from immortalized MDC1A myoblasts, but not
      those formed from immortalized healthy or disease control human myoblasts, showed
      significantly increased activation of caspase-3. This pattern of aberrant caspase
      3 activation in the immortalized cultures was similar to that found previously in
      primary MDC1A cultures and laminin-alpha2-deficient mice. CONCLUSIONS:
      Immortalized MDC1A myogenic cells provide a new resource for studies of
      pathogenetic mechanisms and for screening possible therapeutic approaches in
      laminin-alpha2-deficiency.

PMID- 24314269
TI  - The influence of diabetes mellitus on the management and visual outcome of
      patients with uveitis.

PMID- 24314267
TI  - Clinically relevant intronic splicing enhancer mutation in myelin proteolipid
      protein leads to progressive microglia and astrocyte activation in white and gray
      matter regions of the brain.
AB  - INTRODUCTION: Mutations in proteolipid protein (PLP), the most abundant myelin
      protein in the CNS, cause the X-linked dysmyelinating leukodystrophies, Pelizaeus
      Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2). Point mutations,
      deletion, and duplication of the PLP1 gene cause PMD/SPG2 with varying clinical
      presentation. Deletion of an intronic splicing enhancer (ISEdel) within intron 3
      of the PLP1 gene is associated with a mild form of PMD. Clinical and preclinical
      studies have indicated that mutations in myelin proteins, including PLP, can
      induce neuroinflammation, but the temporal and spatial onset of the reactive glia
      response in a clinically relevant mild form of PMD has not been defined. METHODS:
      A PLP-ISEdel knockin mouse was used to examine the behavioral and
      neuroinflammatory consequences of a deletion within intron 3 of the PLP gene, at
      two time points (two and four months old) early in the pathological progression.
      Mice were characterized functionally using the open field task, elevated plus
      maze, and nesting behavior. Quantitative neuropathological analysis was for
      markers of astrocytes (GFAP), microglia (IBA1, CD68, MHCII) and axons (APP). The
      Aperio ScanScope was used to generate a digital, high magnification
      photomicrograph of entire brain sections. These digital slides were used to
      quantify the immunohistochemical staining in ten different brain regions to
      assess the regional heterogeneity in the reactive astrocyte and microglial
      response. RESULTS: The PLP-ISEdel mice exhibited behavioral deficits in the open
      field and nesting behavior at two months, which did not worsen by four months of
      age. A marker of axonal injury (APP) increased from two months to four months of
      age. Striking was the robust reactive astrocyte and microglia response which was
      also progressive. In the two-month-old mice, the astrocyte and microglia
      reactivity was most apparent in white matter rich regions of the brain. By four
      months of age the gliosis had become widespread and included both white as well
      as gray matter regions of the brain. CONCLUSIONS: Our results indicate, along
      with other preclinical models of PMD, that an early reactive glia response occurs
      following mutations in the PLP gene, which may represent a potentially clinically
      relevant, oligodendrocyte-independent therapeutic target for PMD.

PMID- 24314270
TI  - Addiction-related effects of DOV 216,303 and cocaine: A comparative study in the
      mouse.
AB  - DOV 216,303, an inhibitor of serotonin, noradrenaline and dopamine reuptake,
      belongs to a new line of drugs called 'triple reuptake inhibitors' that have been
      proposed for treatment of depression. The addictive drug cocaine has similar
      mechanism of action and exerts rewarding effects by blocking reuptake of
      dopamine, leading to increased extracellular concentrations of dopamine in the
      nucleus accumbens. Thus, DOV 216,303 and other triple reuptake inhibitors might
      be speculated to exhibit abuse potential, limiting their future therapeutic use.
      To further elucidate potential addictive properties of DOV 216,303, we conducted
      a comparative study of addiction-related effects of DOV 216,303 and cocaine in
      mice using acute self-administration, conditioned place preference (CPP) and drug
      induced hyperlocomotion. Effects on accumbal extracellular dopamine levels were
      determined using microdialysis, and we measured monoamine receptor occupancy as
      well as brain and plasma exposure. DOV 216,303 was self-administered acutely in
      the same dose range as cocaine. However, in the CPP model, DOV 216,303 did not
      induce place preference at doses where cocaine caused place preference. Higher
      doses of DOV 216,303 than cocaine were needed to induce hyperlocomotion and
      increase extracellular accumbal dopamine with effective doses being higher than
      effective doses used in depression models. Moreover, DOV 216,303 displayed a
      pharmacokinetic profile with lower potential for addiction than cocaine. Thus,
      high levels of DAT occupancy were reached slower and decayed more slowly after
      DOV 216,303 than cocaine administration. The present study shows that acute
      administration of DOV 216,303 displays some addictive-like properties in mice,
      but these were less pronounced than cocaine, most likely due to different
      pharmacokinetic profiles.

PMID- 24314272
TI  - Comprehensive transcriptome profiling of squamous cell carcinoma of horn in Bos
      indicus.
AB  - Squamous cell carcinoma (SCC) of horn is frequently observed in Bos indicus
      affecting 1% of cattle population and accounting 83.34% of total tumours found.
      The transcriptome profile of horn cancer (HC) tissue and the matched normal (HN)
      tissue were analysed by RNA-seq using Roche 454 sequencing. A total of 1 504 900
      reads comprising of 612 MB data were used to identify differentially expressed
      genes using CLC Genomic Workbench. These include up-regulation of KRT6A, KRT6B,
      KRT6C, KRT14, SFN, KRT84, PI3, COL17A1, ANLN, SERPINB5 and down-regulation of
      BOLA, SCGB1A1, CXCL17, KRT19, BPIFB1, NR4A1 and TFF3 in HC, which are involved in
      regulation of gene transcription, cell proliferation, apoptosis, cell survival
      and metabolic pathways. The qPCR analysis of several targets suggested
      concordance of gene expression profile with RNA-seq analysis. The present
      findings would provide basis for further screening of genes and identification of
      markers for early diagnosis and therapeutic intervention of HC. 

PMID- 24314271
TI  - Patient confidentiality within the context of group medical visits: is there
      cause for concern?
AB  - BACKGROUND: Group medical visits (GMVs), clinical encounters with a medical
      component delivered to groups of patients, have emerged as an innovative approach
      to potentially increasing efficiency while enhancing the quality of primary
      health care (PHC). GMVs have created the need to pay explicit attention to
      patient confidentiality. OBJECTIVE: What strategies are used by providers and
      patients to address issues of confidentiality within GMVs? DESIGN: In-depth
      interviews were conducted with 34 PHC providers and 29 patients living in nine
      rural communities in British Columbia, Canada. Data were analysed using
      interpretive thematic analysis and a relational autonomy approach. RESULTS: We
      found three main themes: (i) choosing to disclose: balancing benefits and
      drawbacks of GMVs, (ii) maintaining confidentiality in GMVs and (iii) gaining
      strength from interdependent relationships: patients learning from each other.
      Confidentiality can be addressed and was not a major concern for patients
      attending or providers facilitating GMVs in these rural communities. DISCUSSION:
      Patients adopted strategies to address their own and others' concerns related to
      confidential health information. Providers used multiple strategies to maintain
      confidentiality within the group, including renegotiating what information is
      shared and providing examples of what information ought to be kept confidential.
      CONCLUSIONS: Although GMVs are not for all patients, a relational autonomy
      approach is useful in drawing attention to the context and structures which may
      influence their patients' ability to act autonomously. Successful delivery of
      GMVs requires both patients and providers to negotiate between maintaining
      confidentiality and an appropriate level of disclosure.

PMID- 24314273
TI  - L-arginine abolishes the hypothalamic serotonergic activation induced by central
      interleukin-1beta administration to normal rats.
AB  - IL-1beta-induced anorexia may depend on interactions of the cytokine with
      neuropeptides and neurotransmitters of the central nervous system control of
      energy balance and serotonin is likely to be one catabolic mediator targeted by
      IL-1beta. In the complex interplay involved in feeding modulation, nitric oxide
      has been ascribed a stimulatory action, which could be of significance in
      counteracting IL-1beta effects.The present study aims to explore the
      participation of the nitric oxide and the serotonin systems on the central
      mechanisms induced by IL-1beta and the relevance of their putative interactions
      to IL-1beta hypophagia in normal rats.Serotonin levels were determined in
      microdialysates of the ventromedial hypothalamus after a single
      intracerebroventricular injection of 10 ng of IL-1beta , with or without the pre
      injection of 20 MUg of the nitric oxide precursor L-arginine. IL-1beta
      significantly stimulated hypothalamic serotonin extracellular levels, with a peak
      variation of 130 +/- 37% above baseline. IL- 1beta also reduced the 4-h and the
      24-h food intakes (by 23% and 58%, respectively). The IL-1beta-induced
      serotonergic activation was abolished by the pre-injection of L-arginine while
      the hypophagic effect was unaffected.The data showed that one central effect of
      IL-1beta is serotonergic stimulation in the ventromedial hypothalamus, an action
      inhibited by nitric oxide activity. It is suggested that, although serotonin
      participates in IL-1beta anorexia, other mechanisms recruited by IL-1beta in
      normal rats are able to override the absence of the serotonergic hypophagic
      influence.

PMID- 24314274
TI  - Consistency in boldness, activity and exploration at different stages of life.
AB  - BACKGROUND: Animals show consistent individual behavioural patterns over time and
      over situations. This phenomenon has been referred to as animal personality or
      behavioural syndromes. Little is known about consistency of animal personalities
      over entire life times. We investigated the repeatability of behaviour in common
      voles (Microtus arvalis) at different life stages, with different time intervals,
      and in different situations. Animals were tested using four behavioural tests in
      three experimental groups: 1. before and after maturation over three months, 2.
      twice as adults during one week, and 3. twice as adult animals over three months,
      which resembles a substantial part of their entire adult life span of several
      months. RESULTS: Different behaviours were correlated within and between tests
      and a cluster analysis showed three possible behavioural syndrome-axes, which we
      name boldness, exploration and activity. Activity and exploration behaviour in
      all tests was highly repeatable in adult animals tested over one week. In animals
      tested over maturation, exploration behaviour was consistent whereas activity was
      not. Voles that were tested as adults with a three-month interval showed the
      opposite pattern with stable activity but unstable exploration behaviour.
      CONCLUSIONS: The consistency in behaviour over time suggests that common voles do
      express stable personality over short time. Over longer periods however,
      behaviour is more flexible and depending on life stage (i.e. tested before/after
      maturation or as adults) of the tested individual. Level of boldness or activity
      does not differ between tested groups and maintenance of variation in behavioural
      traits can therefore not be explained by expected future assets as reported in
      other studies.

PMID- 24314275
TI  - [Maxillary sinus floor augmentation with Bio-Oss as a sole graft: a histologic,
      radiographic and preliminary clinical study].
AB  - OBJECTIVE: To evaluate new bone formation and preliminary clinical outcomes
      following maxillary sinus floor augmentation with Bio-Oss alone. METHODS: Nine
      patients were treated with ten maxillary sinus floor augmentations using Bio-Oss
      alone, and eighteen Straumann implants were placed. After five to eleven-month
      healing period at implant placement, cylindrical specimens were biopsied from the
      augmented area. The new bone formation of specimens was analyzed by histology and
      micro-computed tomography. Cone beam computed tomography (CBCT) scans were
      performed for measurements of residual crestal bone height under the sinus, the
      amount of increased height immediate after the augmentation and before implant
      insertion. To monitor stability changes, resonance frequency analysis was
      performed and implant stability quotient (ISQ) values were collected at implant
      placements (baseline,0 month), one month, three months and six months after
      placements. RESULTS: All implants were loaded six months after insertion and no
      failures were recorded. Compared to adjacent native bone, no significant
      differences of bone volume fraction were found in augmented area (P > 0.05),
      together with lower trabecular number (P < 0.05) and trabecular thickness (P <
      0.01) as well as higher trabecular separation (P < 0.01) by microradiographic
      analysis.Histomorphometrically, there was no significant difference in the amount
      of new bone formation between the adjacent native bone and augmented area (P >
      0.05). CBCT showed a bone height gain of (14.19 +/- 2.02) mm immediate after
      augmentation, which stabilized at (13.68 +/- 1.95) mm after bone healing period.
      Mean ISQ value was 71.94 +/- 6.51 at baseline, decreased to 70.19 +/- 6.38 at 1
      month, and increased to 78.17 +/- 3.83 at 3 month and 82.56 +/- 3.20 at 6 month.
      CONCLUSIONS: The use of Bio-Oss as the sole graft is reliable and can lead to
      satisfactory bone formation and clinical outcome.

PMID- 24314276
TI  - [Analysis of the plaster casts of Class II division 1 non-extraction patients
      treated with Alexander technique].
AB  - OBJECTIVE: To investigate the changes of arch width and arch length in Class II
      division 1 non-extraction patients treated with Alexander technique. METHODS:
      Dental casts of 21 Class II division 1 non-extraction patients treated with
      Alexander appliance were taken before (T1) and after treatment (T2). All the
      casts were laser scanned. The arch width and arch length were digitally measured.
      The differences of arch width and arch length between T1 and T2 were recorded and
      analyzed. RESULTS: The upper arch length decreased from (32.82 +/- 2.51) mm to
      (31.97 +/- 2.17) mm (P < 0.05). The lower arch length increased from (27.53 +/-
      2.61) mm to (28.80 +/- 1.81) mm (P < 0.05). The intercanine width in the upper
      arch changed significantly from T1 to T2. The intermolar width in the upper and
      lower arches increased significantly from T1 to T2. CONCLUSIONS: Class II
      division 1 non-extraction patients could be treated successfully by increasing
      the upper arch width.

PMID- 24314277
TI  - [Effect of pamidronate and ibandronate on orthodontic root resorption in rats].
AB  - OBJECTIVE: To compare the effects of pamidronate and ibandronate on orthodontic
      root resorption. METHODS: Seventy-two 6-week-old female specific pathogen free
      (SPF) Wistar rats were selected to establish models for orthodontic tooth
      movement. The rats were randomly divided into three groups: the control group (C
      group), pamidronate group (Pm group) and ibandronate group (Ib group). 0.9%
      normal saline,0.5 mmol/L pamidronate and 0.5 mmol/L ibandronate were injected
      every 3 days. The rats were executed in batch on the 3rd, 7th and 14th day to
      make tissue sections. All statistical analysis was performed using the PASW
      Statistics 18 software package. RESULTS: On the 7th and 14th day, the amount of
      cementoclast, the expression of osteoclast differentiation factor (ODF) and root
      resorption index were significantly lower in Pm group [the 7th day: (2.675 +/-
      0.002), (0.1683 +/- 0.0007), (0.103 +/- 0.003); the 14th day: (3.886 +/- 0.048),
      (0.1873 +/- 0.0014), (0.283 +/- 0.001)] and Ib groups[the 7th day: (2.601 +/-
      0.001), (0.1634 +/- 0.0010), (0.099 +/- 0.002); the 14th day: (3.754 +/- 0.019),
      (0.1818 +/- 0.0016), (0.281 +/- 0.001)] than in C group[the 7th day: (2.810 +/-
      0.001), (0.1792 +/- 0.0008), (0.120 +/- 0.001); the 14th day: (4.800 +/- 0.001),
      (0.2060 +/- 0.0007), (0.401 +/- 0.001)] (P < 0.05). However, no significant
      difference was found between Pm and Ib groups on the 3rd, 7th and 14th day (P >
      0.05). CONCLUSIONS: Both pamidronate and ibandronate could inhibit orthodontic
      root resorption.

PMID- 24314278
TI  - [Effect of different stress conditions on growth and biofilm formation capability
      of Enterococcus faecalis].
AB  - OBJECTIVE: To study the changes of growth and biofilm formation capability of
      Enterococcus faecalis (Ef) in different stress conditions. METHODS: The changes
      of growth of Ef in stress conditions were observed by measuring the A600 value
      with ultraviolet spectrophotometer. Ef was incubated on glass slide in stress
      conditions, biofilm formation capability of cells was investigated by colony
      forming unit (CFU) counting of the culturable bacteria and fluorescence confocal
      laser scanning microscopy. RESULTS: Ef couldn't growth under the conditions of
      2%, 5%NaClO, pH = 11 and 12, the A600 value was unchanged in 96 hours. But the
      growth curve changed at different levels in other stress conditions: under
      1%NaClO, the A600 value peaked at 1.461 at 16 hour (the peaked level was 1.238 at
      6 hours in control group) ; under 0,0.05%,0.15% glucose, it peaked at
      0.645,0.890, 1.173, respectively, at 6 hour (it was maximized to 1.195 at 6 hours
      in control group); the A600 value peaked at 1.704 at 6 hours at pH = 9 and 1.225
      at 10 hours at pH = 10 (the peak level was 1.732 at 6 hours at pH = 7) . Biofilm
      assay showed that Ef were able to form biofilm in these stress conditions except
      5%NaClO and pH = 12. CONCLUSIONS: Ef could growth and form biofilms in energy
      starvation, low concentrations of sodium hypochlorite and weak alkaline stress.

PMID- 24314279
TI  - [Emdogain regulates the expression of bone sialoprotein gene in human dental pulp
      cells].
AB  - OBJECTIVE: To analyze the effects of emdogain(EMD) on the expression of the bone
      sialoprotein(BSP) gene in human dental pulp cells and to elucidate the molecular
      mechanism of BSP gene regulated by EMD. METHODS: Human dental pulp was harvested
      from premolars freshly extracted for orthodontic purpose and cultured. Cells were
      divided into different concentrations (25, 50, 100 and 250 mg/L) of EMD and
      control groups (Dulbecco's modified Eagle's medium). Total RNA of cells was
      extracted. Human BSP mRNA levels was detected with the real-time PCR. Regulations
      of EMD on human BSP protein levels were detected with Western blotting. RESULTS:
      In the real-time PCR, at the same time point, there were significant differences
      on BSP mRNA levels between 25, 50, 100 and 250 mg/L EMD groups (7 d:1.79 +/-
      0.03, 2.03 +/- 0.10, 2.67 +/- 0.08, 2.94 +/- 0.07) and control group (7 d:1.06 +/
      0.11) (P < 0.001); at the different time point (1, 3, 5 and 7 d), the same
      dose(250 mg/L) of EMD stimulated human dental pulp cells, BSP mRNA (2.30 +/-
      0.06, 2.65 +/- 0.05, 2.76 +/- 0.05, 2.94 +/- 0.07) was increased (P < 0.05).
      Treatment of human dental pulp cells with EMD (250 mg/L) increased the protein
      levels. CONCLUSIONS: EMD increases BSP mRNA and protein levels in human dental
      pulp cells.

PMID- 24314280
TI  - [Signal transducers and activators of transcription-3 modulates human squamous
      cell carcinoma invasion via targeting mircoRNA-21 in vitro].
AB  - OBJECTIVE: To investigate the effect and mechanism of signal transducers and
      activators of transcription 3 (STAT-3) modulates human tongue squamous cell
      carcinoma invasion ability via targeting mircoRNA-21. METHODS: Tscca and
      Tca8113P160 human tongue squamous cell carcinoma cell lines were used.WP1066
      (STAT-3 inhibitor) , the small molecule inhibitor of STAT-3 was used to suppress
      the STAT-3 expression. The half maximal inhibitory concentration (IC50 value) of
      WP1066 in the two cell lines was determined by methyl thiazolyl tetrazolium (MTT)
      assay. The expression level of STAT-3 and phosphorylation of STAT-3 (pSTAT-3) was
      examined by Western blotting. Real-time PCR was used to detect the mircoRNA-21
      expression after treated with WP1066. Matrigel matrix and transwell assay were
      used to determine cancer cell colony formation and invasion ability after treated
      with WP1066. Tumor invasion related proteins in Tscca and Tca8113P160 cell lines
      were measured by Western blotting. Luciferase reporter gene assay was conducted
      to detect the relationship between STAT-3 and mircoRNA-21. RESULTS: The IC50 to
      WP1066 in Tscca cell was 3.1 and 3.5 umol/L for Tca8113P160 cell respectively.
      STAT-3/pSTAT-3 protein level was suppressed significantly (Tscca: STAT-3: F =
      887.154, P = 0.000; pSTAT-3: F = 332.212, P = 0.000; Tca8113P160: STAT-3: F =
      322.895, P = 0.000; pSTAT-3:F = 788.357, P = 0.000). mircoRNA-21 expression was
      down-regulated (Tscca:F = 32.157, P = 0.000; Tca8113P160: F = 11.349, P = 0.007).
      The diameters of culture clone in cell treated with WP1066 were less than control
      groups (Tscca:F = 15.751, P = 0.004; Tca8113P160: F = 12.964, P = 0.007). The
      number of tongue cancer cell migrating through the transwell membrane in WP1066
      treated group was less than in control groups (Tscca: F = 1688.926, P = 0.000;
      Tca8113P160: F = 327.528, P = 0.000). In addition, MMP-2/9 protein expression was
      decreased in both of the cell lines treated with WP1066, while TIMP-3 was up
      regulated dramatically. STAT-3 could modulate mircoRNA-21 directly. CONCLUSIONS:
      Reduction of STAT-3 can inhibit tongue cancer cell invasion ability via targeting
      mircoRNA-21.

PMID- 24314281
TI  - [The salivary factors related to caries and periodontal disease in children and
      adolescents with diabetes mellitus].
AB  - OBJECTIVE: To detect the salivary factors related to caries and periodontal
      disease and to analyze the risk of caries and periodontal disease in children and
      adolescents with diabetes mellitus. METHODS: The study comprised 30 children with
      diabetic mellitus, aged 7-15 years old, and 60 healthy age-and gender-matched
      children. Caries and periodontal indexes were recorded and saliva related factors
      were analyzed. RESULTS: Caries indexes of diabetes children [permanent teeth:
      decay missing filling tooth (DMFT) M (Q1,Q3) = 0(0, 4), deciduous teeth: decay
      missing filling tooth (dmft) M (Q1,Q3) = 0(0, 1)] were not significantly
      different with those of healthy children [DMFT M (Q1,Q3) = 1(0, 3), dmft M
      (Q1,Q3) = 0(0, 4)], but plaque index (PLI) (1.25 +/- 0.33) and bleeding index
      (BI) (0.74 +/- 0.45) of diabetes children were significantly higher than those of
      healthy children (PLI was 0.93 +/- 0.31,BI was 0.34 +/- 0.22) (P < 0.001).
      Salivary pH of diabetes children (7.68 +/- 0.36) was significantly higher than
      that of healthy children (7.30 +/- 0.32) (P < 0.05), and salivary acid buffering
      capacity had no significant difference between the two groups (P > 0.05).
      Salivary glucose, immunoglobulin sIgA and sIgG were not significantly different
      between the two groups (P > 0.05).Salivary lysozyme of diabetes children was
      significantly higher than that of healthy children (P < 0.05). Total protein was
      significantly lower in diabetes children than in healthy children (P < 0.05).
      Salivary lactate dehydrogenase had no significant difference between the two
      groups (P > 0.05). CONCLUSIONS: Diabetes mellitus can lead to the changes of some
      salivary factors related to gingivitis in diabetes children. Children and
      adolescents with diabetes mellitus may have a higher risk of periodontal disease.

PMID- 24314282
TI  - [Initial evolution research for design and process accuracy of one type of
      domestic computer aided design soft and computer aided manufacture].
AB  - OBJECTIVE: To evaluate the design and manufacture accuracy of a domestic computer
      aided design (CAD) and computer aided manufacture (CAM) system, and to compare it
      with similar foreign products. METHODS: Thirty models of posterior-teeth-single
      crown preparations were collected, and STL data of these preparations was
      collected by Denmark 3Shape scanner. Three copings were made for each
      preparation, the one designed and manufactured using commercial CAD/CAM system
      (3Shape CAD software and Wieland T1 CAM equipment) was assigned into control
      group T0, the one designed and manufactured using domestic CAD software
      (developed by Peking University School and Hospital of Stomatology and Nanjing
      University of Aeronautics and Astronautics) and Wieland T1 CAM equipment was
      assigned into experimental group TCAD for design accuracy evaluation, and the one
      designed and manufactured using 3Shape CAD software and domestic CAM equipment
      (developed by Peking University School and Hospital of Stomatology, Tsinghua
      University and ShanDong XinHua Incorporated Company of medical apparatus and
      instruments) was assigned into experimental group TCAM for manufacture accuracy
      evaluation. Finally, the marginal fitness were compared and evaluated by using 3D
      & Profile measurement microscope laser. RESULTS: The marginal fitness of TCAD was
      27.98 (19.10, 46.57) um in buccal, 32.67 (20.65, 50.82) um in lingual, 27.38
      (22.53, 52.61) um in mesial, 29.50 (22.68, 53.65) um in distal; of TCAM was 21.69
      (15.87, 30.21) um in buccal, 18.51 (13.50, 22.51) um in lingual, 19.15 (15.42,
      26.89) um in mesial, 22.77 (18.58, 32.15) um in distal; and there were no
      statistical differences compared with T0 [20.16 (17.16, 48.00) um in buccal,
      21.51 (17.05, 28.31) um in lingual, 23.54 (17.89, 30.04) um in mesial and 23.94
      (17.93, 28.19) um in distal] except lingual data of TCAD. CONCLUSIONS: The design
      and machining precision of this domestic CAD/CAM system is at the same level of
      those comparable foreign products.

PMID- 24314283
TI  - [Effect of flurbiprofen on preemptive analgesia in teeth extraction under
      intravenous sedation by midazolam].

PMID- 24314284
TI  - [Analysis of 115 adverse drug reactions of oral diseases].

PMID- 24314285
TI  - [Maxillofacial surgery instructed by maxillofacial prosthetic restoration].

PMID- 24314286
TI  - [Ten years of AO cranio-maxillofacial surgery education in China].

PMID- 24314287
TI  - [Surgical approaches in craniofacial fractures: standard incision and the
      modified incision].

PMID- 24314288
TI  - [The mechanism and influencing factors of halitosis].

PMID- 24314289
TI  - [Current research on alveolar bone dehiscences and fenestrations].

PMID- 24314290
TI  - [Advances in collateral damage of laser ablation of dental hard tissues].

PMID- 24314291
TI  - Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune
      modulation.
AB  - BACKGROUND: We previously found that the low frequency magnetic fields (LF-MF)
      inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF
      may modulate immune function so as to inhibit tumor. We here investigated whether
      LF-MF can inhibit the proliferation and metastasis of melanoma and influence
      immune function. METHODS: The effect of MF on the proliferation, cell cycle and
      ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay,
      flow cytometry, and transmission electron microscopy. Lung metastasis mice were
      prepared by injection of 2 * 105 B16-F10 melanoma cells into the tail vein in
      C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days.
      Survival rate, tumor markers and the innate and adaptive immune parameters were
      measured. RESULTS: The growth of B16-F10 cells was inhibited after exposure to
      the LF-MF. The inhibition was related to induction of cell cycle arrest and
      decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival
      rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice
      model. Furthermore, the LF-MF modulated the immune response via regulation of
      immune cells and cytokine production. In addition, the number of Treg cells was
      decreased in mice with the LF-MF exposure, while the numbers of T cells as well
      as dendritic cells were significantly increased. CONCLUSION: LF-MF inhibited the
      growth and metastasis of melanoma cancer cells and improved immune function of
      tumor-bearing mice. This suggests that the inhibition may be attributed to
      modulation of LF-MF on immune function and LF-MF may be a potential therapy for
      treatment of melanoma.

PMID- 24314292
TI  - The retinoic acid receptor-alpha modulators ATRA and Ro415253 reciprocally
      regulate human IL-5+ Th2 cell proliferation and cytokine expression.
AB  - BACKGROUND: Th2 cytokine responses are enhanced by all trans retinoic acid
      (ATRA), the bioavailable form of vitamin A. Retinoic acid receptor alpha
      (RARalpha) is the high affinity receptor for ATRA that mediates these pro-Th2
      effects. We have previously characterized two major human Th2 subpopulations: IL
      5- Th2 (IL-5-, IL-4+, IL-13+) and IL-5+ Th2 cells (IL-5+, IL-4+, IL-13+), which
      represent less and more highly differentiated Th2 cells, respectively. We
      hypothesized that the pro-Th2 effects of ATRA may differentially affect these Th2
      subpopulations. METHODS: Specific cytokine producing Th2 subpopulations were
      identified using intracellular cytokine staining. Proliferation was measured
      using the Cell Trace Violet proliferation tracking dye. Apoptotic cells were
      identified using either annexin-V or active caspase 3 staining. Th2 gene
      expression was measured using quantitative polymerase chain reaction. RESULTS:
      ATRA increased the output of Th2 cells from house dust mite allergen (HDM)
      specific short-term cell lines, and this enhancement was limited to the IL-5+ Th2
      subpopulation. Conversely, the RARalpha antagonist Ro415253 decreased Th2 cell
      output from these cultures, and this effect was again limited to the IL-5+ Th2
      subpopulation. ATRA and Ro415253 respectively augmented and inhibited Th2 cell
      proliferation, and this affect was more pronounced for the IL-5+ vs. IL-5- Th2
      subpopulation. ATRA and Ro415253 respectively augmented and inhibited the
      expression of IL5 in a significant manner, which was not found for IL4 or IL13.
      CONCLUSIONS: We report that the reciprocal regulation of Th2 cytokine expression
      and proliferation by RARalpha modulators are largely limited to modulation of IL
      5 gene expression and to proliferation of the highly differentiated IL-5+ Th2
      subpopulation. These results suggest that RARalpha antagonism is a potential
      means to therapeutically target allergic inflammation. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT01212016.

PMID- 24314293
TI  - Effects of interleukin-4 or interleukin-10 gene therapy on
      trinitrobenzenesulfonic acid-induced murine colitis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is characterized by disturbance of
      pro-inflammatory cytokines and anti-inflammatory cytokines. Previous studies have
      demonstrated the effect of anti-inflammatory cytokines, such as interleukin-10
      (IL-10) or IL-4 on IBD, but their data were controversial. This study further
      investigated the effect of IL-4 (IL-4), IL-10 and their combination on treatment
      of trinitrobenzenesulfonic acid (TNBS)-induced murine colitis. METHODS: pcDNA3.0
      carrying murine IL-4 or IL-10 cDNA was encapsulated with LipofectAMINE 2000 and
      intraperitoneally injected into mice with TNBS-induced colitis. The levels of
      intestinal IL-4 and IL-10 mRNA were confirmed by quantitative-RT-PCR. Inflamed
      tissues were assessed by histology and expression of interferon (IFN)-gamma,
      tumor necrosis factor (TNF)-alpha and IL-6. RESULTS: The data confirmed that IL-4
      or IL-10 over-expression was successfully induced in murine colon tissues after
      intraperitoneal injection. Injections of IL-4 or IL-10 significantly inhibited
      TNBS-induced colon tissue damage, disease activity index (DAI) and body weight
      loss compared to the control mice. Furthermore, expression of IFN-gamma, TNF
      alpha and IL-6 was markedly blocked by injections of IL-4 or IL-10 plasmid.
      However, there was less therapeutic effect in mice injected with the combination
      of IL-4 and IL-10. CONCLUSIONS: These data suggest that intraperitoneal injection
      of IL-4 or IL-10 plasmid was a potential strategy in control of TNBS-induced
      murine colitis, but their combination had less effect.

PMID- 24314295
TI  - Systems biology and reproduction.

PMID- 24314294
TI  - Bone marrow-derived stem cells ameliorate hepatic fibrosis by down-regulating
      interleukin-17.
AB  - BACKGROUND: Accumulating evidences have identified the immunoregulatory features
      of stem cells. In this study, the immunoregulation of bone marrow-derived stem
      cells (BMSCs) transplanted into patients with HBV-related decompensated cirrhosis
      and mouse model of liver injury induced by carbon tetrachloride (CCl4)
      administration was observed. RESULTS: Compared with healthy controls, patients
      with HBV-related decompensated cirrhosis showed significantly higher levels of
      TNF-alpha, IL-12, TGF-beta1, IL-17, and IL-8. However, only IL-17 was markedly
      decreased after autologous BMSCs transplantation during their follow-up. The same
      results were found in the CCl4-treated mice. Furthermore, we found that exogenous
      IL-17 partly abolished the therapeutic effect of BMSCs whereas IL-17-specific
      antibody promoted improvement of liver injury in CCl4-treated mice, resembling
      the therapeutic effect of BMSCs transplantation. CONCLUSIONS: These data
      suggested that BMSCs transplantation induces a decrease of IL-17 level, which at
      least in part delineates the mechanisms of stem cells-mediated therapeutic
      benefit on liver disease.

PMID- 24314296
TI  - Introduction: systems biology and reproduction.

PMID- 24314297
TI  - Big Data analysis on autopilot?

PMID- 24314298
TI  - Evaluation of approaches for estimating the accuracy of genomic prediction in
      plant breeding.
AB  - BACKGROUND: In genomic prediction, an important measure of accuracy is the
      correlation between the predicted and the true breeding values. Direct
      computation of this quantity for real datasets is not possible, because the true
      breeding value is unknown. Instead, the correlation between the predicted
      breeding values and the observed phenotypic values, called predictive ability, is
      often computed. In order to indirectly estimate predictive accuracy, this latter
      correlation is usually divided by an estimate of the square root of heritability.
      In this study we use simulation to evaluate estimates of predictive accuracy for
      seven methods, four (1 to 4) of which use an estimate of heritability to divide
      predictive ability computed by cross-validation. Between them the seven methods
      cover balanced and unbalanced datasets as well as correlated and uncorrelated
      genotypes. We propose one new indirect method (4) and two direct methods (5 and
      6) for estimating predictive accuracy and compare their performances and those of
      four other existing approaches (three indirect (1 to 3) and one direct (7)) with
      simulated true predictive accuracy as the benchmark and with each other. RESULTS:
      The size of the estimated genetic variance and hence heritability exerted the
      strongest influence on the variation in the estimated predictive accuracy.
      Increasing the number of genotypes considerably increases the time required to
      compute predictive accuracy by all the seven methods, most notably for the five
      methods that require cross-validation (Methods 1, 2, 3, 4 and 6). A new method
      that we propose (Method 5) and an existing method (Method 7) used in animal
      breeding programs were the fastest and gave the least biased, most precise and
      stable estimates of predictive accuracy. Of the methods that use cross-validation
      Methods 4 and 6 were often the best. CONCLUSIONS: The estimated genetic variance
      and the number of genotypes had the greatest influence on predictive accuracy.
      Methods 5 and 7 were the fastest and produced the least biased, the most precise,
      robust and stable estimates of predictive accuracy. These properties argue for
      routinely using Methods 5 and 7 to assess predictive accuracy in genomic
      selection studies.

PMID- 24314300
TI  - Multicenter macular ganglion cell analysis: normative paediatric reference range.

PMID- 24314299
TI  - Serum level of adiponectin is a surrogate independent biomarker of radiographic
      disease progression in early rheumatoid arthritis: results from the ESPOIR
      cohort.
AB  - INTRODUCTION: Adipokines such as adiponectin, leptin, and visfatin/nicotinamide
      phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory
      mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed
      to determine whether serum adipokine levels independently predicted early
      radiographic disease progression in early RA. METHODS: In total, 791 patients
      were included from the prospective Etude et Suivi des POlyarthrites
      Indifferenciees Recentes (ESPOIR) cohort who met the American College of
      Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had
      undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay
      (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and
      visfatin/NAMPT. In the RA group, we tested the association of serum adipokine
      levels and (a) baseline radiographic damage and (b) radiographic disease
      progression, defined as a change >0 or >= 5 in total Sharp-van der Heijde Score
      (?SHS) between inclusion and 1 year (?SHS >=1 or rapid radiographic progression:
      ?SHS >=5), adjusting for confounders (age, sex, body-mass index, insulin
      resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health
      Assessment Questionnaire score, autoantibody status, steroid use, and
      radiographic evidence of RA damage at inclusion). RESULTS: Adiponectin level was
      independently associated with baseline total SHS (adjusted beta = 0.12; P =
      0.006). It was also associated with ?SHS >=1 (adjusted odds ratio (aOR) = 1.84
      (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR =
      1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin
      level predicted ?SHS >=5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was
      independently associated only with ?SHS >0 (aOR = 1.59 (1.05 to 2.42)).
      Conversely, serum visfatin/NAMPT level and radiographic disease progression were
      unrelated. Considering the receiver-operated characteristic curves, the best
      adiponectin cut-offs were 4.14 MUg/ml for ?SHS >=1 and 6.04 MUg/ml for ?SHS >=5,
      with a good specificity (58% and 75% for ?SHS >=1 and ?SHS >=5, respectively) and
      high negative predictive values (75% and 92% for ?SHS >=1 or ?SHS >=5,
      respectively). CONCLUSION: Serum adiponectin level is a simple useful biomarker
      associated with early radiographic disease progression in early RA, independent
      of RA-confounding factors and metabolic status.

PMID- 24314301
TI  - Using an audience response system to improve learning success in practical skills
      training courses in dental studies - a randomised, controlled cross-over study.
AB  - INTRODUCTION: The aim of this study was to examine whether the use of an audience
      response system (ARS) in a high-quality study design, in a course in pre-clinical
      dentistry leads to an improvement in cognitive and psycho-motor performance.
      MATERIALS AND METHODS: As part of the Phantom Course I, a randomised, controlled
      study in cross-over design with 63 students was conducted over 4 weeks. The
      intervention was carried out by means of an ARS (TurningPoint((r)) ), while a
      verbal question-and-answer session was conducted within the control group.
      Differences in learning success were determined via a formative multiple-choice
      (MC) test (cognitive) and a summative practical test (psycho-motor). RESULTS:
      Both groups achieved significantly better results in the MC tests with the use of
      the intervention, when compared with the control group (group A 11.6 vs. 9.5 and
      group B 13.7 vs. 12.1, maximum 16 points). A further analysis of the results
      showed that the overall effect was induced primarily by a marked improvement in
      below-average students. The practical tests showed no clear effect. Despite the
      careful selection and set-up of the conditions for the study in the regular
      course of the semester, a cohort effect emerged. This was due to varying degrees
      of performance between the two groups, because no adequate performance parameters
      were available, which could have been taken into account for the stratified
      randomisation. CONCLUSIONS: The results indicate that the use of the ARS leads to
      better results in cognitive performance, especially where independent learning is
      required and should be encouraged. Weaker students in particular seem to benefit.

PMID- 24314302
TI  - Diagram-based Analysis of Causal Systems (DACS): elucidating inter-relationships
      between determinants of acute lower respiratory infections among children in sub
      Saharan Africa.
AB  - BACKGROUND: Effective interventions require evidence on how individual causal
      pathways jointly determine disease. Based on the concept of systems epidemiology,
      this paper develops Diagram-based Analysis of Causal Systems (DACS) as an
      approach to analyze complex systems, and applies it by examining the
      contributions of proximal and distal determinants of childhood acute lower
      respiratory infections (ALRI) in sub-Saharan Africa. RESULTS: Diagram-based
      Analysis of Causal Systems combines the use of causal diagrams with multiple
      routinely available data sources, using a variety of statistical techniques. In a
      step-by-step process, the causal diagram evolves from conceptual based on a
      priori knowledge and assumptions, through operational informed by data
      availability which then undergoes empirical testing, to integrated which
      synthesizes information from multiple datasets. In our application, we apply
      different regression techniques to Demographic and Health Survey (DHS) datasets
      for Benin, Ethiopia, Kenya and Namibia and a pooled World Health Survey (WHS)
      dataset for sixteen African countries. Explicit strategies are employed to make
      decisions transparent about the inclusion/omission of arrows, the sign and
      strength of the relationships and homogeneity/heterogeneity across
      settings.Findings about the current state of evidence on the complex web of socio
      economic, environmental, behavioral and healthcare factors influencing childhood
      ALRI, based on DHS and WHS data, are summarized in an integrated causal diagram.
      Notably, solid fuel use is structured by socio-economic factors and increases the
      risk of childhood ALRI mortality. CONCLUSIONS: Diagram-based Analysis of Causal
      Systems is a means of organizing the current state of knowledge about a specific
      area of research, and a framework for integrating statistical analyses across a
      whole system. This partly a priori approach is explicit about causal assumptions
      guiding the analysis and about researcher judgment, and wrong assumptions can be
      reversed following empirical testing. This approach is well-suited to dealing
      with complex systems, in particular where data are scarce.

PMID- 24314303
TI  - Health-related characteristics and unmet needs of men with erectile dysfunction:
      a survey in five European countries.
AB  - INTRODUCTION: Data suggest that ED is still an underdiagnosed and undertreated
      condition. In addition, it seems that men with ED are unsatisfied about their
      relationship with their physician and with the available drugs. AIM: The study
      aims to identify health-related characteristics and unmet needs of patients
      suffering from erectile dysfunction (ED) in big 5 European Union (EU) nations
      (France, Germany, Italy, Spain, and UK). METHODS: Data were collected from the
      2011 5EU National Health and Wellness-Survey on a population of 28,511 adult men
      (mean age: 47.18; SD 16.07) and was focused on men (5,184) who self-reported ED
      in the past 6 months. In addition, the quality of life (QoL) and work
      productivity/activity were explored. MAIN OUTCOME MEASURES: Health-related QoL
      (HRQoL) and work productivity were measured with SF-12v2 and WPAI validated
      psychometric tools. RESULTS: One in every 20 young men (age 18-39) across 5EU
      experienced ED in the past 6 months. About half of men (2,702/5,184; [52%]) with
      ED across all ages did not discuss their condition with their physician.
      Interestingly, among those men who did discuss their condition with their
      physician, 68% (1,668/2,465) do not currently use medication. These findings were
      more evident in the age group of 18-39 years. Only 48% (2,465/5,184) had a closer
      relationship with their physician, suggesting that this quality of relationship
      may be unsatisfactory. Compared with controls, ED patients have a significantly
      higher intrapsychic and relational psychopathological comorbid burden and
      relevant decreasing in HRQoL, with a significantly higher impairment on work
      productivity/activity. CONCLUSION: Data suggest that there is a need for a new
      therapeutic paradigm in ED treatment which images the achievement of a new
      alliance between physician and patient. Hence, alternative drug delivery
      strategies may reduce the psychological and social impact of this disease.

PMID- 24314304
TI  - Hepatic angiomyolipoma and neurofibromatosis type 2: a novel association.

PMID- 24314305
TI  - Evaluating performance of dental caries detection methods among third-year dental
      students.
AB  - BACKGROUND: Reliable caries detection is a cornerstone in the modern caries
      treatment schema. This study aimed to evaluate adopting traditional and new
      caries detection methods by third-year dental students. METHODS: Fifty-seven
      students were given lectures on caries detection, after which they evaluated 27
      extracted carious teeth using traditional clinical assessment (CE), Nyvad's, and
      ICDAS methods. On three teeth they also performed DIAGNOdent pen(r) (LF)
      scanning. Histological scores of the sectioned teeth (ICDAS, LF) and activity
      estimations of the lesions by the supervisors were used as golden standards
      (Nyvad, CE). For the ICDAS method , sensitivity and specificity were calculated
      using dentine caries (D3) as a cut-off point. Mean ICC and kappa values were
      calculated to evaluate interexaminer agreement for all lesions and methods.
      Spearman's correlation coefficient evaluated LF scanning. RESULTS: ICDAS method
      presented good sensitivity (0.78) and specificity (0.87). The inter-examiner
      agreement for different methods was fair or good (CE ICC = 0.69, kappa = 0.53;
      Nyvad's method ICC = 0.68, kappa = 0.48, ICDAS ICC = 0.66, kappa = 0.47).
      Variation in LF values was the greatest with lesions extending to middle third of
      dentin. In that case, the Spearman's correlation coefficient was also the
      weakest. CONCLUSIONS: To follow the guidelines by the European Core Curriculum on
      Cariology, the third year dental students are introduced to methods for detecting
      lesion depth and assessing lesion activity as well as using new caries detection
      methods. Their performance in estimating lesion depth is good, and fair to good
      in estimating lesion activity even after basic training only.

PMID- 24314306
TI  - Physical activity levels during pregnancy and gestational weight gain among women
      who are overweight or obese.
AB  - ISSUE ADDRESSED: There is contradictory research assessing physical activity
      patterns during pregnancy and postpartum among women who are overweight or obese.
      The aim of this study was to evaluate physical activity among overweight and
      obese women over the course of pregnancy and the initial postpartum period.
      METHODS: Three hundred and five overweight or obese pregnant women completed
      physical-activity questionnaires at three time points during pregnancy and at 4
      months postpartum. RESULTS: Physical activity declined between early pregnancy
      and 28-weeks gestation (P<0.001) and declined further at 36-weeks gestation
      (P<0.001) before increasing significantly at 4-months postpartum (P<0.001).
      However, reported activity at 4-months postpartum remained significantly lower
      than that reported in early pregnancy (P<0.001). There was no significant
      difference either cross-sectionally or for changes over pregnancy and postpartum
      for total levels or categories of physical activity for women with different body
      mass index (BMI) or gestational weight gain (GWG). BMI was the only independent
      predictor of the change in total physical activity over the study and GWG, with
      women with higher BMI having larger decline of physical activity (beta=0.114,
      s.e.=0.750, P=0.032) and less GWG (beta=-0.253, s.e.=0.063, P<0.001).
      CONCLUSIONS: Physical activity declined significantly between early pregnancy and
      28-weeks gestation, with a further decline to 36-weeks gestation. At 4-months
      postpartum, physical activity significantly increased but not to the level of
      that reported at early pregnancy. SO WHAT?: The promotion of appropriate physical
      activity should be implemented early in pregnancy and postpartum to prevent the
      decline in activity we have observed in overweight and obese women. Future
      research should also explore the barriers and enablers to women engaging in
      exercise during pregnancy and the postpartum period.

PMID- 24314307
TI  - S-1 combined with docetaxel following doxorubicin plus cyclophosphamide as
      neoadjuvant therapy in breast cancer: phase II trial.
AB  - BACKGROUND: This study evaluated the efficacy and safety of S-1 combined with
      docetaxel (SD) following doxorubicin plus cyclophosphamide (AC) as neoadjuvant
      therapy in patients with HER2-negative, stage II-III breast cancer. METHODS:
      Patients received AC every 3 weeks for four cycles followed by S-1 (30 mg/m2
      orally b.i.d. on days 1-14) and docetaxel (75 mg/m2 i.v. on day 1) every 3 weeks
      for four cycles. The primary endpoint was the pathological complete response
      (pCR) rate in breast and axillary lymph nodes. RESULTS: The study included 49
      patients with a median age of 43 years. The median breast tumor size was 4.0 cm
      by palpation. All patients were positive for involvement of axillary lymph node
      and five patients also had supraclavicular lymph node metastasis, which was
      confirmed by histological examination. In total, 85.4% of patients (41/49)
      completed eight cycles of therapy and 95.9% of patients (47/49) received curative
      surgery. The pCR rate was 22.5% (n = 11). The clinical response rate was 67.4%.
      During SD chemotherapy, the most frequent grade 3-4 toxicity was neutropenia
      (8.5% by cycle). There was a single treatment-related mortality from severe
      neutropenia. Grade 3 S-1 specific toxicities such as epigastric pain (12.2% by
      person), stomatitis (4.1% by person), and diarrhea (2.0% by person) were also
      observed. In particular, gastrointestinal discomfort led to dose reduction of S-1
      in 45.8% of patients. CONCLUSIONS: Given all axillary lymph node positive
      diseases, neoadjuvant S-1 combined with docetaxel following AC showed a favorable
      anti-tumor activity but gastrointestinal discomfort should be carefully
      considered for future studies. TRIAL REGISTRATION: NCT00994968.

PMID- 24314308
TI  - A nationwide population-based study of the inflammatory bowel diseases between
      1998 and 2008 in Taiwan.
AB  - BACKGROUND: The incidence of the inflammatory bowel diseases (IBD), ulcerative
      colitis (UC) and Crohn's disease (CD), has been increasing in Asia. We probed the
      nationwide registered database to assess the incidence, prevalence, gender
      distribution, age of diagnosis and the survival status of IBD patients in Taiwan.
      METHODS: A retrospective study was conducted to analyze the registered database
      compiled by the National Health Insurance provided by the Department of Health,
      Taiwan, from January 1998 through December 2008. RESULTS: A total of 1591 IBD
      patients were registered from 1998 to 2008 in Taiwan (CD: 385; UC: 1206). The
      incidence of CD increased from 0.19/100,000 in 1998 to 0.24/100,000 in 2008. The
      incidence of UC increased from 0.61/100,000 in 1998 to 0.94/100,000 in 2008. The
      prevalence of CD increased from 0.19/100,000 in 1998 to 1.78/100,000 in 2008. The
      prevalence of UC increased from 0.61/100,000 in 1998 to 7.62/100,000 in 2008.
      Male to female ratio for CD was 2.22 and 1.64 for UC. Age of registered for CD
      was predominantly between 20 to 39, and for UC between 30 to 49 years of age. The
      standardized mortality ratio (95% CI) was 4.97 (3.72-6.63) for CD and 1.78 (1.46
      2.17) for UC, from 1998 to 2008 in Taiwan. CONCLUSIONS: Using the Taiwan
      nationwide database for IBD, the incidence and prevalence of IBD in Taiwan
      significantly increased from 1998 to 2008. The mortality rate was higher for CD
      patients than UC patients, and both were higher than the general population.

PMID- 24314309
TI  - Attitudes toward evidence-based clinical practice among doctors of chiropractic
      with diplomate-level training in orthopedics.
AB  - BACKGROUND: Evidence-based clinical practice (EBCP) is a practice model gaining
      prominence within healthcare, including the chiropractic profession. The status
      of EBCP has been evaluated in a variety of healthcare disciplines, but little is
      known regarding the attitudes doctors of chiropractic (DCs) hold toward this
      model of healthcare. This project examines the attitudes toward EBCP within a
      specialty discipline of DCs. METHODS: We identified a survey questionnaire
      previously used to evaluate EBCP among non-chiropractic complementary and
      alternative practitioners. We adapted this questionnaire for use among DCs and
      pretested it in 5 chiropractic college faculty. The final version was
      administered to DCs with diplomate-level training in orthopedics. The survey was
      emailed to 299 potential participants; descriptive results were calculated.
      RESULTS: 144 surveys were returned, resulting in a 48% response rate. The
      majority of respondents perceived EBCP as an important aspect of chiropractic
      practice. Respondents also believed themselves to have an above average skill
      level in EBCP, reported that training originated from their diplomate education,
      and based the majority of their practice on clinical research. CONCLUSION:
      Doctors of chiropractic with an orthopedic diplomate appear to have favorable
      attitudes toward EBCP. Further study will help understand EBCP perceptions among
      general field DCs. A logical next step includes validation of this questionnaire.

PMID- 24314311
TI  - Advances in circulating tumor cells (ACTC): from basic research to clinical
      practice.
AB  - The first 'Advances in Circulating Tumor Cells (ACTC): from Basic Research to
      Clinical Practice' meeting was held in Athens, Greece, September 26-29, 2012
      (abstracts, presentations and a more detailed meeting report are freely available
      online: http://www.actc2012.org). We summarize in this report most major findings
      presented and the main conclusions derived during the expert panel sessions. 

PMID- 24314310
TI  - Characterization of CurcuEmulsomes: nanoformulation for enhanced solubility and
      delivery of curcumin.
AB  - BACKGROUND: Curcumin is a polyphenolic compound isolated from the rhizomes of the
      plant Curcuma longa and shows intrinsic anti-cancer properties. Its medical use
      remains limited due to its extremely low water solubility and bioavailability.
      Addressing this problem, drug delivery systems accompanied by nanoparticle
      technology have emerged. The present study introduces a novel nanocarrier system,
      so-called CurcuEmulsomes, where curcumin is encapsulated inside the solid core of
      emulsomes. RESULTS: CurcuEmulsomes are spherical solid nanoparticles with an
      average size of 286 nm and a zeta potential of 37 mV. Encapsulation increases the
      bioavailability of curcumin by up to 10,000 fold corresponding to a concentration
      of 0.11 mg/mL. Uptaken by HepG2 human liver carcinoma cell line, CurcuEmulsomes
      show a significantly prolonged biological activity and demonstrated therapeutic
      efficacy comparable to free curcumin against HepG2 in vitro - with a delay in
      response, as assessed by cell viability, apoptosis and cell cycle studies. The
      delay is attributed to the solid character of the nanocarrier prolonging the
      release of curcumin inside the HepG2 cells. CONCLUSIONS: Incorporation of
      curcumin into emulsomes results in water-soluble and stable CurcuEmulsome
      nanoformulations. CurcuEmulsomes do not only successfully facilitate the delivery
      of curcumin into the cell in vitro, but also enable curcumin to reach its
      effective concentrations inside the cell. The enhanced solubility of curcumin and
      the promising in vitro efficacy of CurcuEmulsomes highlight the potential of the
      system for the delivery of lipophilic drugs. Moreover, high degree of
      compatibility, prolonged release profile and tailoring properties feature
      CurcuEmulsomes for further therapeutic applications in vivo.

PMID- 24314312
TI  - How do vitrectomy parameters influence the results of rhegmatogenous retinal
      detachments repair? EVRS RD Study No. 3.

PMID- 24314313
TI  - Online exercise for the design and simulation of PCR and PCR-RFLP experiments.
AB  - BACKGROUND: Polymerase Chain Reaction (PCR) and Restriction Fragment Length
      Polymorphism of PCR products (PCR-RFLP) are extensively used molecular biology
      techniques. An exercise for the design and simulation of PCR and PCR-RFLP
      experiments will be a useful educational tool. FINDINGS: An online PCR and PCR
      RFLP exercise has been create that requires users to find the target genes,
      compare them, design primers, search for restriction endonucleases, and finally
      to simulate the experiment. Each user of the service is randomly assigned a gene
      from Escherichia coli; to complete the exercise, users must design an experiment
      capable of distinguishing among E. coli strains. By applying the experimental
      procedure to all completely sequenced E. coli, a basic understanding of strain
      comparison and clustering can also be acquired. Comparison of results obtained in
      different experiments is also very instructive. CONCLUSIONS: The exercise is
      freely available at http://insilico.ehu.es/edu.

PMID- 24314315
TI  - Arrhythmias and sudden death among older children and young adults following
      tetralogy of Fallot repair in the current era: are previously reported risk
      factors still applicable?
AB  - BACKGROUND: Young adult patients (pts) with repaired tetralogy of Fallot (TOF)
      remain at risk for arrhythmias (Ar) and sudden cardiac death (SCD). Based on past
      studies with earlier pt subsets, Ar/SCD events were associated with right
      ventricular (RV) systolic pressures >60 mm Hg, outflow tract gradients >20 mm Hg,
      and QRS duration >180 ms. However, there are limited recent studies to evaluate
      these risk factors in the current patient generation. METHODS: Patients with TOF
      followed over the past 50 years were grouped by presence of any arrhythmias
      (group 1), absence of arrhythmias (group 2), and presence of SCD or significant
      ventricular arrhythmias (group 3) and correlated with current pt age, gender, age
      at repair, repair types, echocardiogram, cardiac magnetic resonance imaging,
      electrocardiogram/Holter, hemodynamics, and electrophysiology findings. RESULTS:
      Of 109 pts, 52 were male aged 17-58 years. Of these, 59 (54%) had Ar, two of whom
      had SCD. These 59 pts were chronologically older at the time of analysis, with
      repair at an older age and wider QRS duration (78-240, mean 158 ms) when compared
      with those without Ar. However, there was no correlation with surgical era,
      surgical repair, gender, RV pressure >60 mm Hg, right ventricular outflow tract
      gradient >20 mm Hg, or RV end-diastolic volume on CMRI. CONCLUSIONS: Ar/SCD risk
      continues to correlate with repair age and advancing pt age. QRS duration is
      longer in these patients but at a shorter interval (mean 158 ms) and less RV
      pressure (mean 43 mm Hg) than previously reported. In the current TOF patient
      generation, neither surgical era, type of repair, RV outflow gradient nor RV
      volume correlate with Ar/SCD. Electrophysiologic testing to verify and identify
      arrhythmias remains clinically effective.

PMID- 24314316
TI  - Hepatoprotective action of Panaxatriol saponins against acetaminophen-induced
      liver injury: what is the mechanism?

PMID- 24314314
TI  - The role of Dichaete in transcriptional regulation during Drosophila embryonic
      development.
AB  - BACKGROUND: Group B Sox domain transcription factors play conserved roles in the
      specification and development of the nervous system in higher metazoans. However,
      we know comparatively little about how these transcription factors regulate gene
      expression, and the analysis of Sox gene function in vertebrates is confounded by
      functional compensation between three closely related family members. In
      Drosophila, only two group B Sox genes, Dichaete and SoxN, have been shown to
      function during embryonic CNS development, providing a simpler system for
      understanding the functions of this important class of regulators. RESULTS: Using
      a combination of transcriptional profiling and genome-wide binding analysis we
      conservatively identify over 1000 high confidence direct Dichaete target genes in
      the Drosophila genome. We show that Dichaete plays key roles in CNS development,
      regulating aspects of the temporal transcription factor sequence that confer
      neuroblast identity. Dichaete also shows a complex interaction with Prospero in
      the pathway controlling the switch from stem cell self-renewal to neural
      differentiation. Dichaete potentially regulates many more genes in the Drosophila
      genome and was found to be associated with over 2000 mapped regulatory elements.
      CONCLUSIONS: Our analysis suggests that Dichaete acts as a transcriptional hub,
      controlling multiple regulatory pathways during CNS development. These include a
      set of core CNS expressed genes that are also bound by the related Sox2 gene
      during mammalian CNS development. Furthermore, we identify Dichaete as one of the
      transcription factors involved in the neural stem cell transcriptional network,
      with evidence supporting the view that Dichaete is involved in controlling the
      temporal series of divisions regulating neuroblast identity.

PMID- 24314317
TI  - Pregnancy outcome after use of cranberry in pregnancy--the Norwegian Mother and
      Child Cohort Study.
AB  - BACKGROUND: Cranberry is one of the most commonly used herbs during pregnancy.
      The herb has been used traditionally against urinary tract infections. No studies
      are found that specifically address the risk of malformations after use of
      cranberry during pregnancy. The aim of the study was to investigate the safety of
      cranberry use during pregnancy, including any effects on congenital malformations
      and selected pregnancy outcomes. METHODS: The study is based on data from The
      Norwegian Mother and Child Cohort Study including more than 100,000 pregnancies
      from 1999 to 2008. Information on use of cranberry and socio-demographic factors
      was retrieved from three self-administered questionnaires completed by the women
      in pregnancy weeks 17 and 30, and 6 months after birth. Information on pregnancy
      outcomes was retrieved from the Medical Birth Registry of Norway. RESULTS: Among
      the 68,522 women in the study, 919 (1.3%) women had used cranberry while
      pregnant. We did not detect any increased risk of congenital malformations after
      use of cranberry. Furthermore, the use of cranberry was also not associated with
      increased risk for stillbirth/neonatal death, low birth weight, small for
      gestational age, preterm birth, low Apgar score (<7), neonatal infections or
      maternal vaginal bleeding in early pregnancy. Although an association was found
      between use of cranberry in late pregnancy and vaginal bleeding after pregnancy
      week 17, further sub-analyses of more severe bleeding outcomes did not support a
      significant risk. CONCLUSIONS: The findings of this study, revealing no increased
      risk of malformations nor any of the following pregnancy outcomes;
      stillbirth/neonatal death, preterm delivery, low birth weight, small for
      gestational age, low Apgar score and neonatal infections are reassuring. However,
      maternal vaginal bleeding should be investigated further before any firm
      conclusion can be drawn. Treatment guidelines on asymptomatic bacteriuria in
      pregnancy recommend antimicrobial therapy as the first line treatment. According
      to our data and the outcomes studied, cranberry does not appear to be a harmful
      adjunctive self-treatment.

PMID- 24314318
TI  - Is early detection of abused children possible?: a systematic review of the
      diagnostic accuracy of the identification of abused children.
AB  - BACKGROUND: Early detection of abused children could help decrease mortality and
      morbidity related to this major public health problem. Several authors have
      proposed tools to screen for child maltreatment. The aim of this systematic
      review was to examine the evidence on accuracy of tools proposed to identify
      abused children before their death and assess if any were adapted to screening.
      METHODS: We searched in PUBMED, PsycINFO, SCOPUS, FRANCIS and PASCAL for studies
      estimating diagnostic accuracy of tools identifying neglect, or physical,
      psychological or sexual abuse of children, published in English or French from
      1961 to April 2012. We extracted selected information about study design, patient
      populations, assessment methods, and the accuracy parameters. Study quality was
      assessed using QUADAS criteria. RESULTS: A total of 2 280 articles were
      identified. Thirteen studies were selected, of which seven dealt with physical
      abuse, four with sexual abuse, one with emotional abuse, and one with any abuse
      and physical neglect. Study quality was low, even when not considering the lack
      of gold standard for detection of abused children. In 11 studies, instruments
      identified abused children only when they had clinical symptoms. Sensitivity of
      tests varied between 0.26 (95% confidence interval [0.17-0.36]) and 0.97 [0.84
      1], and specificity between 0.51 [0.39-0.63] and 1 [0.95-1]. The sensitivity was
      greater than 90% only for three tests: the absence of scalp swelling to identify
      children victims of inflicted head injury; a decision tool to identify physically
      abused children among those hospitalized in a Pediatric Intensive Care Unit; and
      a parental interview integrating twelve child symptoms to identify sexually
      abused children. When the sensitivity was high, the specificity was always
      smaller than 90%. CONCLUSIONS: In 2012, there is low-quality evidence on the
      accuracy of instruments for identifying abused children. Identified tools were
      not adapted to screening because of low sensitivity and late identification of
      abused children when they have already serious consequences of maltreatment.
      Development of valid screening instruments is a pre-requisite before considering
      screening programs.

PMID- 24314319
TI  - Improving care after hip fracture: the fracture? Think osteoporosis (FTOP)
      program.
AB  - BACKGROUND: Hip fractures are a common and serious consequence of osteoporosis,
      and hip fracture patients are at high risk for recurrence. Appropriate
      pharmacotherapy reduces this risk and is associated with reduced mortality after
      hip fracture, but a care gap exists for fracture prevention in these patients.
      This evaluation determined rates of osteoporosis treatment and bone mineral
      density (BMD) testing in hip fracture patients following discharge from a
      rehabilitation unit. METHODS: A prospective cohort study of hip fracture patients
      aged >= 50 on an inpatient rehabilitation unit in 2008 and 2011. Patients were
      seen by a nurse specialist, and encouraged to see their family physician for
      further assessment and treatment. Physicians were sent a letter indicating the
      need to follow up with their patient. Patients were contacted following discharge
      from hospital to determine treatment rates. RESULTS: Of 310 eligible hip fracture
      patients admitted to the rehabilitation unit in the years studied, 207 patients
      were reached post-discharge and provided data. Of patients who were not
      previously taking osteoporosis medication, 59% of patients from the 2008 cohort,
      and 42% of patients from the 2011 cohort had osteoporosis treatment initiated by
      six months following discharge. By 2 months following discharge, 46% of patients
      in the 2008 cohort had a new BMD performed or scheduled, while this was true for
      14% of patients from the 2011 cohort. 35% of patients in 2011 had not seen their
      family physician by 2 months following discharge. CONCLUSIONS: Rates for
      osteoporosis treatment and BMD testing were higher than those reported in the
      literature for patients not enrolled in case manager programs. BMD testing
      declined from 2008 to 2011. Lower treatment rates may be due to concerns
      regarding reports of possible association between bisphosphonate use and atypical
      fractures. Improving rates of patient follow-up with family physicians will be
      important for increasing hip fracture treatment rates after discharge.

PMID- 24314320
TI  - Activation of transsulfuration pathway by salvianolic acid a treatment: a
      homocysteine-lowering approach with beneficial effects on redox homeostasis in
      high-fat diet-induced hyperlipidemic rats.
AB  - BACKGROUND: Elevated homocysteine is a cardiovascular risk factor in
      hyperlipidemia. Transsulfuration pathway provides an endogenous pathway for
      homocysteine conversion to antioxidant glutathione (GSH). Salvianolic acid A (Sal
      A) contains two molecules of caffeic acid and one molecule of danshensu that is
      capable of enhancing homocysteine transsulfuration, which led to the hypothesis
      that Sal A has activatory effect on transsulfuration pathway and this effect may
      have beneficial effects on both homocysteine and redox status in hyperlipidemia.
      METHODS AND RESULTS: To test this hypothesis, we developed a rat model of
      hyperlipidemia induced by high-fat diet for 16 weeks, during which rats were
      treated with 1 mg/kg salvianolic acid A (Sal A) for the final 4 weeks. Activities
      of key enzymes and metabolite profiling in the transsulfuration pathway revealed
      that hyperlipidemia led to elevated plasma homocysteine levels after 16-week
      dietary treatment, which was associated with reduced activities of homocysteine
      transsulfuration enzymes, cystathionine beta-synthase (CBS) and cystathionine
      gamma-lyase (CSE). The impaired transsulfuration pathway prevented homocysteine
      transsulfuration to cysteine, resulting in cysteine deficiency and subsequent
      reduction in GSH pool size. The redox status was altered in the setting of
      hyperlipidemia as indicated by GSH/GSSG ratio. Sal A treatment increased hepatic
      CBS and CSE activities, which was associated with reduced accumulation in
      circulating homocysteine levels and attenuated decline in hepatic cysteine
      content in hyperlipidemic rats. Sal A also led to an increase in GSH pool size,
      which subsequently caused a restored GSH/GSSG ratio. The activatory effect of Sal
      A on CBS was also observed in normal rats and in in vitro experiment. CONCLUSION:
      Our results suggest that activation of transsulfuration pathway by Sal A is a
      promising homocysteine-lowering approach that has beneficial effects on redox
      homeostasis in hyperlipidemic settings.

PMID- 24314321
TI  - Between desire and rape - narratives about being intimate partners and becoming
      pregnant in a violent relationship.
AB  - BACKGROUND: Women subjected to intimate partner violence (IPV) experience
      different forms of abuse. Sexual violence is often under-reported because
      physically abused women, in particular, might see forced sex as an obligatory
      part of the sexual interplay. Accordingly, abused women have less sexual autonomy
      and experience unplanned pregnancies more often than other women. OBJECTIVE: To
      describe and analyse nine Swedish women's retrospective stories about IPV with a
      focus on power and coping strategies as intimate partners, particularly regarding
      experiences of sex, contraception, and becoming pregnant. Design : Nine
      qualitative interviews were carried out with women who had been subjected to very
      severe violence in their intimate relationships and during at least one
      pregnancy. The stories were analysed using 'Narrative method' with the emphasis
      on the women's lived experiences. RESULTS: Despite the violence and many
      contradictory and ambivalent feelings, two of the women described having sex as
      desirable, reciprocal and as a respite from the rest of the relationship. The
      other seven women gave a negative and totally different picture, and they viewed
      sex either as obligatory or as a necessity to prevent or soothe aggression or
      referred to it as rape and as something that was physically forced upon them. The
      women's descriptions of their pregnancies ranged from being carefully planned and
      mostly wanted to completely unwelcome and including flawed contraceptive efforts
      with subsequent abortions. CONCLUSIONS: Women subjected to IPV have diverse and
      complex experiences that have effects on all parts of the relationship. Intimacy
      might for some turn into force and rape, but for others sex does not necessarily
      exclude pleasure and desire and can be a haven of rest from an otherwise violent
      relationship. Accordingly, women may tell stories that differ from the ones
      expected as 'the typical abuse story', and this complexity needs to be recognized
      and dealt with when women seek healthcare, especially concerning contraceptives,
      abortions, and pregnancies.

PMID- 24314322
TI  - Public awareness and attitudes towards epilepsy in Tehran, Iran.
AB  - BACKGROUND: Epilepsy is a prototypical, stigmatised disorder. Numerous studies
      have been conducted regarding the public perception of epilepsy, but they are
      primarily from high-income western countries; few studies have taken place in low
      to middle-income countries with a traditional culture and a religious
      orientation. OBJECTIVE: The public knowledge and attitudes towards epilepsy in
      Tehran, Iran, is studied. DESIGN: A survey of 800 subjects ranging from 18 to 85
      years was randomly chosen from households in Tehran in 2009. The questionnaire
      used was based on the Caveness and Gallup's studies conducted in the United
      States in 1949 and it has been used in numerous similar studies all over the
      world. The mean age of the participants was 37.5 years and 46.7% were female.
      Pearson's Chi-squared test was used for subgroup analyses. RESULTS: The majority
      of subjects cited brain disorders as a cause of epilepsy, while 17% indicated the
      will of God as the cause. Most individuals were willing to work with a person
      with epilepsy, allow their children to play with a child with epilepsy, and allow
      people with epilepsy to use public transportation (78-82%). However, only 28%
      were willing to accept the marriage of a family member to someone with epilepsy.
      CONCLUSION: The knowledge and attitudes towards epilepsy are similar to those in
      Europe, with the exception of a much lower acceptance regarding marriage to a
      person with epilepsy. However, the low acceptance for marrying someone with
      epilepsy reveals the remaining misconceptions about the nature of epilepsy in
      Iran, despite the high educational level in the studied population. Therefore,
      informational efforts must be employed to change the perception of epilepsy.

PMID- 24314324
TI  - De novo characterization of the gene-rich transcriptomes of two color-polymorphic
      spiders, Theridion grallator and T. californicum (Araneae: Theridiidae), with
      special reference to pigment genes.
AB  - BACKGROUND: A number of spider species within the family Theridiidae exhibit a
      dramatic abdominal (opisthosomal) color polymorphism. The polymorphism is
      inherited in a broadly Mendelian fashion and in some species consists of dozens
      of discrete morphs that are convergent across taxa and populations. Few genomic
      resources exist for spiders. Here, as a first necessary step towards identifying
      the genetic basis for this trait we present the near complete transcriptomes of
      two species: the Hawaiian happy-face spider Theridion grallator and Theridion
      californicum. We mined the gene complement for pigment-pathway genes and examined
      differential expression (DE) between morphs that are unpatterned (plain yellow)
      and patterned (yellow with superimposed patches of red, white or very dark
      brown). RESULTS: By deep sequencing both RNA-seq and normalized cDNA libraries
      from pooled specimens of each species we were able to assemble a comprehensive
      gene set for both species that we estimate to be 98-99% complete. It is likely
      that these species express more than 20,000 protein-coding genes, perhaps 4.5%
      (ca. 870) of which might be unique to spiders. Mining for pigment-associated
      Drosophila melanogaster genes indicated the presence of all ommochrome pathway
      genes and most pteridine pathway genes and DE analyses further indicate a
      possible role for the pteridine pathway in theridiid color patterning.
      CONCLUSIONS: Based upon our estimates, T. grallator and T. californicum express a
      large inventory of protein-coding genes. Our comprehensive assembly illustrates
      the continuing value of sequencing normalized cDNA libraries in addition to RNA
      seq in order to generate a reference transcriptome for non-model species. The
      identification of pteridine-related genes and their possible involvement in color
      patterning is a novel finding in spiders and one that suggests a biochemical link
      between guanine deposits and the pigments exhibited by these species.

PMID- 24314323
TI  - The role of tumor-associated macrophages in tumor vascularization.
AB  - Tumor vascularization is a highly complex process that involves the interaction
      between tumors and their surrounding stroma, as well as many distinct
      angiogenesis-regulating factors. Tumor associated macrophages (TAMs) represent
      one of the most abundant cell components in the tumor environment and key
      contributors to cancer-related inflammation. A large body of evidence supports
      the notion that TAMs play a critical role in promoting the formation of an
      abnormal tumor vascular network and subsequent tumor progression and invasion.
      Clinical and experimental evidence has shown that high levels of infiltrating
      TAMs are associated with poor patient prognosis and tumor resistance to
      therapies. In addition to stimulating angiogenesis during tumor growth, TAMs
      enhance tumor revascularization in response to cytotoxic therapy (e.g.,
      radiotherapy), thereby causing cancer relapse. In this review, we highlight the
      emerging data related to the phenotype and polarization of TAMs in the tumor
      microenvironment, as well as the underlying mechanisms of macrophage function in
      the regulation of the angiogenic switch and tumor vascularization. Additionally,
      we discuss the potential of targeting pro-angiogenic TAMs, or reprograming TAMs
      toward a tumoricidal and angiostatic phenotype, to promote normalization of the
      tumor vasculature to enhance the outcome of cancer therapies. 

PMID- 24314325
TI  - Combination of pulse cyclophosphamide and azathioprine in ocular manifestations
      of Behcet's disease: longitudinal study of up to 10 years.
AB  - AIM: Ocular lesions of Behcet's disease (BD) need aggressive treatment to prevent
      severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic
      agents and the first line treatment. Retinal vasculitis is the most aggressive
      lesion of ocular manifestations and predicts a worse systemic outcome. We present
      here the outcome with a combination of pulse cyclophosphamide, azathioprine and
      prednisolone, on long-term usage, up to 10 years, on 295 patients (18 493 eye
      months of follow-up). METHODS: Cyclophosphamide was used as a 1-g monthly pulse
      for 6 months and then every 2-3 months as necessary. Azathioprine was used at 2-3
      mg/kg daily. Prednisolone was initiated at 0.5 mg/kg daily. Upon the suppression
      of the inflammatory reaction, prednisolone was tapered gradually. Patients
      fulfilled the International Criteria Behcet's Disease (ICBD) and had active
      posterior uveitis (PU) and/or retinal vasculitis (RV). Visual acuity (VA), PU, RV
      and TADAI (Total Adjusted Disease Activity Index) were calculated. RESULTS:
      Overall results: mean VA improved from 3.5 to 4.3 (P < 0.0001), 44% of eyes
      improved (95% CI = 40-50). Mean PU improved from 2.1 to 0.8 (P < 0.0001), 73% of
      eyes improved (95% CI = 69-78). Mean RV improved from 3.0 to 1.4 P < 0.0001), 70%
      of eyes improved (95% CI = 65-74). Mean TADAI improved from 29 to 18 (P <
      0.0001), 72% of patients improved (95% CI = 66-77). The details of the
      longitudinal studies are given in the main article. CONCLUSION: All parameters
      significantly improved. VA improvement was the least, mainly due to cataracts.
      This combination is the best treatment choice for retinal vasculitis before
      opting for biologic agents.

PMID- 24314326
TI  - Epidemiological evidence relating snus to health--an updated review based on
      recent publications.
AB  - An earlier review summarized evidence relating use of snus (Swedish-type moist
      snuff) to health and to initiation and cessation of smoking. This update
      considers the effect recent publications on snus use and health have on the
      overall evidence. The additional evidence extends the list of neoplastic
      conditions unassociated with snus use (oropharynx, oesophagus, stomach, lung) to
      include colorectal cancer and acoustic neuroma, and further undermines the weakly
      based argument that snus use increases the risk of pancreatic cancer, although
      there is a report of poorer cancer survival in users. It remains undemonstrated
      that "snuff-dipper's lesion" increases risk of oral cancer, and recent
      publications add to the evidence that snus use has no effect on periodontitis or
      dental caries. Although onset of acute myocardial infarction is not adversely
      associated with snus use, there is some evidence of an association with reduced
      survival. Whether this is a direct effect of snus use or a result of confounding
      by socioeconomic status or other factors requires further investigation, as does
      a report of an increased risk of heart failure in snus users. Even if some
      adverse health effects of snus use do exist, it remains clear that they are far
      less than those of smoking. 

PMID- 24314328
TI  - Refining the role of BRCA1 in combating oxidative stress.
AB  - The BRCA1 hereditary susceptibility gene has been studied in great depth,
      befitting its clear role in promoting basal type breast cancer and serous type
      ovarian (fallopian tube) cancer in women carrying germline mutations. The BRCA1
      protein has long been implicated in maintaining genome integrity through DNA
      repair processes. However, a number of studies have demonstrated that BRCA1 is
      also involved in the response to oxidative stress. A recent paper by Gorrini and
      colleagues extends our mechanistic understanding of how BRCA1 regulates this
      pathway. The relative contribution of this activity in BRCA1-associated
      tumorigenesis and DNA damage response remains unknown. 

PMID- 24314327
TI  - Medical students, spirituality and religiosity--results from the multicenter
      study SBRAME.
AB  - BACKGROUND: To evaluate the relationship between spirituality/religiosity (S/R)
      and the attitudes, beliefs and experiences of medical students in Brazil with
      respect to S/R in their undergraduate training and clinical practice. METHODS:
      SBRAME (Spirituality and Brazilian Medical Education) is a multicenter study
      involving 12 Brazilian medical schools with 5950 medical students (MS).
      Participants completed a questionnaire that collected information on socio
      demographic data and S/R in their undergraduate training and practice. RESULTS:
      Of all MS, 3630 participated in the survey (61.0%). The sample was 53.8% women
      and the mean age was 22.5 years. The majority of MS believed that spirituality
      has an impact on patients' health (71.2%) and that this impact was positive
      (68.2%). The majority also wanted to address S/R in their clinical practice
      (58.0%) and considered it relevant (75.3%), although nearly one-half (48.7%) felt
      unprepared to do so. Concerning their training, most MS reported that they had
      never participated in a "spirituality and health" activity (81.0%) and that their
      medical instructors had never or rarely addressed this issue (78.3%). The
      majority also believed that they should be prepared to address spiritual issues
      related to the health of their patients (61.6%) and that this content should be
      included in the medical curriculum (62.6%). CONCLUSION: There is a large gap
      between MS attitudes and expectations and the S/R training that they are
      receiving during their undergraduate training. The majority of MS surveyed
      believe that patients should have their beliefs addressed and that these beliefs
      could have important effects on their health and the doctor-patient relationship.
      These results should stimulate discussion about the place that S/R training
      should have in the medical curriculum.

PMID- 24314329
TI  - Predictors of oedema among children hospitalized with severe acute malnutrition
      in Jimma University Hospital, Ethiopia: a cross sectional study.
AB  - BACKGROUND: Severe acute malnutrition has two main clinical manifestations, i.e.,
      oedematous and non-oedematous. However, factors associated with oedema are not
      well established. METHODS: Children 0.5-14 years of age with SAM (MUAC < 11.0 cm
      or weight-for-height < 70 % of median and/or nutritional oedema) admitted to the
      nutrition unit were included. Information on infections before and during
      admission was collected together with anthropometry. Predictors of oedema was
      analysed separately for younger (< 60 months) and older children (>= 60 months).
      RESULTS: 351 children were recruited (median age: 36 months (interquartile range
      24 to 60); 43.3% females). Oedema was detected in 61.1%. The prevalence of oedema
      increased with age, peaked at 37-59 months (75%) and declined thereafter.
      Infection was more common in the younger group (33% vs. 8.9%, p < 0.001) and in
      this group children with oedema had less infections (25.2% vs. 45.1%, p = 0.001).
      In the older group the prevalence of infections was not different between
      oedematous and non-oedematous children (5.5% v. 14.3%, p = 0.17). In the younger
      group oedema was less common in children with TB (OR = 0.20, 95% CI: 0.06, 0.70)
      or diarrhea (OR = 0.40, 95% CI: 0.21, 0.73). CONCLUSIONS: The proportion of
      oedema in SAM peaked at three to five years of age and a considerable proportion
      was above 5 years. Furthermore, the prevalence of infection seemed to be lower
      among children with oedema. Further studies are needed to better understand the
      role of infection-immunity interaction.

PMID- 24314330
TI  - Reproducibility and reliability of SNP analysis using human cellular DNA at or
      near nanogram levels.
AB  - BACKGROUND: Illumina SNP arrays have been routinely used for genome-wide
      association studies to identify potential biomarkers for various diseases. The
      recommended 200 ng of DNA for high-quality results is a roadblock to utilizing
      this assay when such quantities of DNA are not available. The goal of this study
      is to determine the reproducibility and reliability of the assay when reduced
      amounts of DNA are used for the SNP arrays. FINDINGS: A serial 3-fold reduction
      of DNA from 200 ng to 0.8 ng was used for an Illumina SNP array in duplicates
      (200 ng, 66.7 ng, 22,2 ng, and 7.4 ng) or triplicates (2.47 ng and 0.8 ng). The
      reproducibility of the assay was determined by comparing allele calls (genotypes)
      at each locus within the duplicates or triplicates. The reliability of samples of
      reduced quantity was determined by comparing allele calls from samples of
      different quantities. As expected, the reproducibility and reliability both
      decrease with decreasing amounts of DNA used for the arrays. However, results of
      comparable quality to the 200 ng DNA recommended by Illumina can be obtained with
      much reduced amounts of DNA. CONCLUSION: Reasonably reproducible and reliable
      results can be obtained with quantities of DNA, as low as 0.8 ng (equivalent to
      133 human cells), well below the manufacturer's recommendation. Results of nearly
      equal quality to that of using 200 ng DNA can be obtained with 22.2 ng of DNA
      reliably, and clearly acceptable data can be obtained using 7.4 ng of DNA for
      Illumina SNP arrays.

PMID- 24314331
TI  - "Call me Ishmael": in the realm of outliers.

PMID- 24314332
TI  - The heat is (still) on--the past and future of hyperthermic radiation oncology.

PMID- 24314334
TI  - Greater trochanteric pain syndrome: does imaging-identified pathology influence
      the outcome of interventions?
AB  - AIM: To assess the outcomes for patients seen in a rheumatology service
      presenting with features of the greater trochanteric pain syndrome (GTPS) and the
      impact of imaging results on the outcomes of treatment. METHODS: Retrospective
      audit, using a phone interview was performed to establish links between results
      of imaging undertaken in the diagnostic work-up of patients with lateral hip pain
      and clinical outcomes for these patients. Patient perceptions of the
      effectiveness of interventions were also assessed. RESULTS: Forty-five patients
      were included (82% female, mean age 69.6 years). Sixty-nine percent underwent
      radiological work-up, including plain X-rays (55%), computed tomography scans
      (64%), magnetic resonance imaging (48%) and ultrasound (90%). Coexistent
      trochanteric bursitis (TB) and gluteal tendinopathy were the most commonly
      elucidated pathologies accounting for the symptomatic presentation of 40% of
      patients. Forty-one patients underwent some form of intervention, most commonly
      injection of local anesthetic and corticosteroid (LACS) into the region of the TB
      (87%), two-thirds of which were undertaken under radiological guidance. Pain
      reduction was maximal following the third injection, with a significantly better
      response to unguided interventions and levels of symptomatic relief following the
      first injection being a good indicator of the probability of complete remission.
      Radiological demonstration of isolated TB correlated with a greater reduction in
      lateral hip symptoms following LACS TB injections both in the immediate post
      injection phase and in the long-term. CONCLUSION: The results of this audit
      suggest that the management of GTPS has reasonable patient outcomes; however, a
      prospective study with greater patient numbers is needed to confirm these
      results.

PMID- 24314335
TI  - The effects of sign language on spoken language acquisition in children with
      hearing loss: a systematic review protocol.
AB  - BACKGROUND: Permanent childhood hearing loss affects 1 to 3 per 1000 children and
      frequently disrupts typical spoken language acquisition. Early identification of
      hearing loss through universal newborn hearing screening and the use of new
      hearing technologies including cochlear implants make spoken language an option
      for most children. However, there is no consensus on what constitutes optimal
      interventions for children when spoken language is the desired outcome.
      Intervention and educational approaches ranging from oral language only to oral
      language combined with various forms of sign language have evolved. Parents are
      therefore faced with important decisions in the first months of their child's
      life. METHODS/DESIGN: This article presents the protocol for a systematic review
      of the effects of using sign language in combination with oral language
      intervention on spoken language acquisition. Studies addressing early
      intervention will be selected in which therapy involving oral language
      intervention and any form of sign language or sign support is used. Comparison
      groups will include children in early oral language intervention programs without
      sign support. The primary outcomes of interest to be examined include all
      measures of auditory, vocabulary, language, speech production, and speech
      intelligibility skills. We will include randomized controlled trials, controlled
      clinical trials, and other quasi-experimental designs that include comparator
      groups as well as prospective and retrospective cohort studies. Case-control,
      cross-sectional, case series, and case studies will be excluded. Several
      electronic databases will be searched (for example, MEDLINE, EMBASE, CINAHL,
      PsycINFO) as well as grey literature and key websites. We anticipate that a
      narrative synthesis of the evidence will be required. We will carry out meta
      analysis for outcomes if clinical similarity, quantity and quality permit
      quantitative pooling of data. We will conduct subgroup analyses if possible
      according to severity/type of hearing disorder, age of identification, and type
      of hearing technology. DISCUSSION: This review will provide evidence on the
      effectiveness of using sign language in combination with oral language therapies
      for developing spoken language in children with hearing loss who are identified
      at a young age. The information from this review can provide guidance to parents
      and intervention specialists, inform policy decisions and provide directions for
      future research. PROSPERO REGISTRATION NUMBER: CRD42013005426.

PMID- 24314336
TI  - Comparative effectiveness research in oncology: the promise, challenges, and
      opportunities.

PMID- 24314337
TI  - An overview of methods for comparative effectiveness research.
AB  - Comparative effectiveness research (CER) is a broad category of outcomes research
      encompassing many different methods employed by researchers and clinicians from
      numerous disciplines. The goal of cancer-focused CER is to generate new knowledge
      to assist cancer stakeholders in making informed decisions that will improve
      health care and outcomes of both individuals and populations. There are numerous
      CER methods that may be used to examine specific questions, including randomized
      controlled trials, observational studies, systematic literature reviews, and
      decision sciences modeling. Each has its strengths and weaknesses. To both inform
      and serve as a reference for readers of this issue of Seminars in Radiation
      Oncology as well as the broader oncology community, we describe CER and several
      of the more commonly used approaches and analytical methods. 

PMID- 24314338
TI  - Decision analysis and cost-effectiveness analysis for comparative effectiveness
      research--a primer.
AB  - Although the analysis of real-world data is the foundation of comparative
      effectiveness analysis, not all clinical questions are easily approached with
      patient-derived information. Decision analysis is a set of modeling and analytic
      tools that simulate treatment and disease processes, including the incorporation
      of patient preferences, thus generating optimal treatment strategies for varying
      patient, disease, and treatment conditions. Although decision analysis is
      informed by evidence-derived outcomes, its ability to test treatment strategies
      under different conditions that are realistic but not necessarily reported in the
      literature makes it a useful and complementary technique to more standard data
      analysis. Similarly, cost-effectiveness analysis is a discipline in which the
      relative costs and benefits of treatment alternatives are rigorously compared.
      With the well-recognized increase in highly technical, costly radiation therapy
      technologies, the cost-effectiveness of these different treatments would come
      under progressively more scrutiny. In this review, we discuss the theoretical and
      practical aspects of decision analysis and cost-effectiveness analysis, providing
      examples that highlight their methodology and utility. 

PMID- 24314339
TI  - Comparative effectiveness research in radiation oncology: assessing technology.
AB  - Technological advances are a major contributor to rising costs in health care,
      including radiation oncology. Despite the large amount spent on new technologies,
      technology assessment remains inadequate, leading to potentially costly and
      unnecessary use of new technologies. Comparative effectiveness studies have an
      important role to play in evaluating the benefits and harms of new technologies
      compared with older technologies and have been identified as a priority area for
      research by the Radiation Oncology Institute. This article outlines the elements
      of effective technology assessment, identifies key challenges to comparative
      effectiveness studies of new radiation oncology technologies, and reviews several
      examples of comparative effectiveness studies in radiation oncology, including
      studies on conformal radiation, IMRT, proton therapy, and other concurrent new
      technologies. 

PMID- 24314340
TI  - Comparative effectiveness research in radiation oncology: stereotactic
      radiosurgery, hypofractionation, and brachytherapy.
AB  - Radiation oncology encompasses a diverse spectrum of treatment modalities,
      including stereotactic radiosurgery, hypofractionated radiotherapy, and
      brachytherapy. Though all these modalities generally aim to do the same thing
      treat cancer with therapeutic doses of radiation while relatively sparing normal
      tissue from excessive toxicity, the general radiobiology and physics underlying
      each modality are distinct enough that their equivalence is not a given. Given
      the continued innovation in radiation oncology, the comparative effectiveness of
      these modalities is important to review. Given the broad scope of radiation
      oncology, this article focuses on the 3 most common sites requiring radiation
      treatment: breast, prostate, and lung cancer. 

PMID- 24314341
TI  - Comparative effectiveness research: opportunities in surgical oncology.
AB  - Comparative effectiveness research (CER) is especially applicable to surgical
      oncology because of the numerous challenges associated with conducting surgical
      randomized controlled trials, and the opportunity to apply various CER
      methodologies to answer surgical questions. In this article, several past
      randomized trials or attempted trials are described to demonstrate challenges
      related to feasibility, patient selection and generalizability, and timeliness
      trial results to inform clinical practice. Thus, there is a gap between these
      "efficacy" studies (ie, randomized trials) and "effectiveness" research, which is
      performed in a less controlled setting (not randomized) but is able to examine
      patient outcomes in the "real world." Retrospective analyses and pragmatic trials
      are other important methods for answering CER questions in surgical oncology,
      with examples of these studies being conducted in prostate, breast, and rectal
      cancers. Multiple current initiatives by the American College of Surgeons and the
      Alliance for Clinical Trials in Oncology continue to expand the infrastructure
      for CER in surgical oncology. 

PMID- 24314342
TI  - Comparative effectiveness research: moving medical oncology forward.
AB  - Comparative effectiveness research (CER) is critically needed in medical oncology
      to improve the care being delivered to oncology patients. As medical oncologists
      are forced to rely on insufficient data as a part of daily treatment decision
      making, and as the cancer treatment landscape evolves quickly relative to other
      areas of medicine, CER is particularly pressing in our field. Continued reliance
      on randomized clinical trials is a part of the solution, but it cannot be the
      sole answer. As new and richer data sources become available addressing quality
      of life, resource utilization, and other critical elements, the implementation of
      CER will advance. Its true power will lie in linkages to "learning health
      systems" and real-time application to the day-to-day practice of medicine. 

PMID- 24314343
TI  - Comparative effectiveness research in practice and policy for radiation oncology.
AB  - Interest in comparative effectiveness research (CER) has increased dramatically
      over the past decade, yet perceptions about what comprises CER varies. CER has
      several attributes relevant to practice and policy: (1) The goal of CER is to
      inform decisions about health care. (2) Literature synthesis is used in addition
      to primary research. (3) CER evaluates not only overall outcomes for the
      population but also evaluates subgroups that may have heterogeneous outcomes. (4)
      Research places an emphasis on outcomes in the "real-world" settings. (5)
      Outcomes studied should be relevant to patients. In radiation oncology, where
      many of the traditional clinical trials are comparative in nature, the line
      between CER and "traditional" research may be blurred, but an increased emphasis
      on CER can help to bridge the research enterprise and clinical practice, helping
      to inform decision making at the patient, clinician, and policy levels. 

PMID- 24314344
TI  - Effects of information, education, and communication campaign on a community
      based health insurance scheme in Burkina Faso.
AB  - OBJECTIVE: The study analysed the effect of Information, Education, and
      Communication (IEC) campaign activities on the adoption of a community-based
      health insurance (CHI) scheme in Nouna, Burkina Faso. It also identified the
      factors that enhanced or limited the campaign's effectiveness. DESIGN:
      Complementary data collection approaches were used. A survey was conducted with
      250 randomly selected household heads, followed by in-depth interviews with 22
      purposively selected community leaders, group discussions with the project
      management team, and field observations. Bivariate analysis and multivariate
      logistic regression models were used to assess the association between household
      exposure to campaign and acquisition of knowledge as well as household exposure
      to campaign and enrolment. RESULTS: The IEC campaign had a positive effect on
      households' knowledge about the CHI and to a lesser extent on household enrolment
      in the scheme. The effectiveness of the IEC strategy was mainly influenced by:
      (1) frequent and consistent IEC messages from multiple media channels (mass and
      interpersonal channels), including the radio, a mobile information van, and CHI
      team, and (2) community heads' participation in the CHI scheme promotion.
      Education was the only significantly influential socio-demographic determinant of
      knowledge and enrolment among household heads. The relatively low effects of the
      IEC campaign on CHI enrolment are indicative of other important IEC mediating
      factors, which should be taken into account in future CHI campaign evaluation.
      CONCLUSION: The study concludes that an IEC campaign is crucial to improving the
      understanding of the CHI scheme concept, which is an enabler to enrolment, and
      should be integrated into scheme designs and evaluations.

PMID- 24314345
TI  - Paternalism, autonomy and reciprocity: ethical perspectives in encounters with
      patients in psychiatric in-patient care.
AB  - BACKGROUND: Psychiatric staff members have the power to decide the options that
      frame encounters with patients. Intentional as well as unintentional framing can
      have a crucial impact on patients' opportunities to be heard and participate in
      the process. We identified three dominant ethical perspectives in the normative
      medical ethics literature concerning how doctors and other staff members should
      frame interactions in relation to patients; paternalism, autonomy and
      reciprocity. The aim of this study was to describe and analyse statements
      describing real work situations and ethical reflections made by staff members in
      relation to three central perspectives in medical ethics; paternalism, autonomy
      and reciprocity. METHODS: All staff members involved with patients in seven adult
      psychiatric and six child and adolescent psychiatric clinics were given the
      opportunity to freely describe ethical considerations in their work by keeping an
      ethical diary over the course of one week and 173 persons handed in their
      diaries. Qualitative theory-guided content analysis was used to provide a
      description of staff encounters with patients and in what way these encounters
      were consistent with, or contrary to, the three perspectives. RESULTS: The
      majority of the statements could be attributed to the perspective of paternalism
      and several to autonomy. Only a few statements could be attributed to
      reciprocity, most of which concerned staff members acting contrary to the
      perspective. The result is presented as three perspectives containing eight
      values.*Paternalism; 1) promoting and restoring the health of the patient, 2)
      providing good care and 3) assuming responsibility.*Autonomy; 1) respecting the
      patient's right to self-determination and information, 2) respecting the
      patient's integrity and 3) protecting human rights.*Reciprocity; 1) involving
      patients in the planning and implementation of their care and 2) building trust
      between staff and patients. CONCLUSIONS: Paternalism clearly appeared to be the
      dominant perspective among the participants, but there was also awareness of
      patients' right to autonomy. Despite a normative trend towards reciprocity in
      psychiatry throughout the Western world, identifying it proved difficult in this
      study. This should be borne in mind by clinics when considering the need for
      ethical education, training and supervision.

PMID- 24314346
TI  - Genetic variation in the atrial natriuretic peptide transcription factor GATA4
      modulates amygdala responsiveness in alcohol dependence.
AB  - BACKGROUND: Two genome-wide association studies recently showed alcohol
      dependence to be associated with a single-nucleotide polymorphism (rs13273672)
      located on a gene (GATA4) that encodes a transcription factor of atrial
      natriuretic peptide (ANP). A growing body of evidence suggests that ANP might be
      involved in the symptomology of alcohol dependence. This study examined whether
      reactivity to alcohol cues in the ANP target region amygdala, a key area
      implicated in addictive behavior, differs depending on the GATA4 genotype of a
      patient. We also investigated potential associations between these differences in
      amygdala activation and relapse behavior. METHODS: Eighty-one abstinent, alcohol
      dependent patients completed a functional magnetic resonance imaging cue
      reactivity task in a 3-Tesla scanner and provided blood samples for DNA
      extraction. RESULTS: The results showed significantly lower alcohol-cue-induced
      activations in G-allele carriers as compared with AA-homozygotes in the bilateral
      amygdala. A survival analysis revealed that a stronger alcohol-specific amygdala
      response predicted a lowered risk for relapse to heavy drinking in the AA
      homozygotes, whereas this effect could not be observed in G-allele carriers.
      CONCLUSIONS: These results illuminate potential underlying mechanisms of the
      involvement of the GATA4 gene in the etiology of alcohol dependence via its
      influence on ANP and amygdala processing.

PMID- 24314347
TI  - Effects of stimulants on brain function in attention-deficit/hyperactivity
      disorder: a systematic review and meta-analysis.
AB  - BACKGROUND: Psychostimulant medication, most commonly the catecholamine agonist
      methylphenidate, is the most effective treatment for attention
      deficit/hyperactivity disorder (ADHD). However, relatively little is known on the
      mechanisms of action. Acute effects on brain function can elucidate underlying
      neurocognitive effects. We tested methylphenidate effects relative to placebo in
      functional magnetic resonance imaging (fMRI) during three disorder-relevant tasks
      in medication-naive ADHD adolescents. In addition, we conducted a systematic
      review and meta-analysis of the fMRI findings of acute stimulant effects on ADHD
      brain function. METHODS: The fMRI study compared 20 adolescents with ADHD under
      either placebo or methylphenidate in a randomized controlled trial while
      performing stop, working memory, and time discrimination tasks. The meta-analysis
      was conducted searching PubMed, ScienceDirect, Web of Knowledge, Google Scholar,
      and Scopus databases. Peak coordinates of clusters of significant effects of
      stimulant medication relative to placebo or off medication were extracted for
      each study. RESULTS: The fMRI analysis showed that methylphenidate significantly
      enhanced activation in bilateral inferior frontal cortex (IFC)/insula during
      inhibition and time discrimination but had no effect on working memory networks.
      The meta-analysis, including 14 fMRI datasets and 212 children with ADHD, showed
      that stimulants most consistently enhanced right IFC/insula activation, which
      also remained for a subgroup analysis of methylphenidate effects alone. A more
      lenient threshold also revealed increased putamen activation. CONCLUSIONS:
      Psychostimulants most consistently increase right IFC/insula activation, which
      are key areas of cognitive control and also the most replicated neurocognitive
      dysfunction in ADHD. These neurocognitive effects may underlie their positive
      clinical effects.

PMID- 24314348
TI  - Acute effects of heroin on negative emotional processing: relation of amygdala
      activity and stress-related responses.
AB  - BACKGROUND: Negative emotional states and abnormal stress reactivity are central
      components in drug addiction. The brain stress system in the amygdala is thought
      to play a key role in the maintenance of drug dependence through negative
      reinforcement. Although acute heroin administration was found to reduce anxiety,
      craving, and stress hormone release, whether these effects are reflected in
      amygdala activity has not yet been investigated. METHODS: With a randomized,
      crossover, double-blind design, saline and heroin were administered to 22 heroin
      dependent patients, whereas 17 healthy control subjects were included for the
      placebo administration only. We used functional magnetic resonance imaging to
      investigate blood oxygen level-dependent responses during fearful faces
      processing. Stress reactivity was measured by adrenocorticotropic hormone levels
      and by cortisol concentrations in serum and saliva 60 min after substance
      administration. Anxiety and craving levels were assessed with self-report
      ratings. RESULTS: Heroin administration acutely reduced the left amygdala
      response to fearful faces relative to the saline injection. Patients receiving
      saline showed a significantly higher left amygdala response to fearful faces than
      healthy control subjects, whose activity did not differ from patients receiving
      heroin. The left amygdala activity correlated significantly with scores on state
      anxiety and levels of adrenocorticotropic hormone, serum cortisol, and saliva
      cortisol among all patients and control subjects. CONCLUSIONS: Our results show a
      direct relation between the acute heroin effects on stress-related emotions,
      stress reactivity, and left amygdala response to negative facial expressions.
      These findings provide new insights into the mechanisms underlying negative
      reinforcement in heroin addiction and the effects of regular heroin substitution.

PMID- 24314350
TI  - Rapid diagnosis of sepsis using biomarker signatures.
AB  - Diagnosis of sepsis is complicated by non-specific clinical definitions and
      delays in laboratory analysis using tests which may have very poor predictive
      values. The use of host biomarker signature sets, which when measured in
      combination have high predictive values, offers a paradigm shift forwards for
      rapid, near-patient diagnosis. These analyses more closely mirror the rapid blood
      chemistry and hematology analyses which often are used for near-patient testing
      and diagnosis. 

PMID- 24314353
TI  - JCL Roundtable: diagnosis of severe familial hypercholesterolemia.
AB  - The diagnosis of familial hypercholesterolemia is usually straightforward. The
      severely elevated low-density lipoprotein cholesterol and the occurrence of high
      concentrations of low-density lipoprotein cholesterol in the parents provide the
      diagnosis. The presence of tendon xanthomata is confirmation but not necessary.
      However, this relatively simple picture becomes much more complicated when one
      attempts to define the genetic variants that actually produced this clinical
      syndrome. In this Roundtable discussion, I am joined by two experts in the
      identification of genetic abnormalities discovered in those with phenotypic
      familial hypercholesterolemia. Dr. John Kane from the University of California,
      San Francisco, and Dr. Daniel Rader from the University of Pennsylvania share
      their knowledge in and experience with this topic. 

PMID- 24314349
TI  - Global resting-state functional magnetic resonance imaging analysis identifies
      frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive
      disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with regional
      hyperactivity in cortico-striatal circuits. However, the large-scale patterns of
      abnormal neural connectivity remain uncharacterized. Resting-state functional
      connectivity studies have shown altered connectivity within the implicated
      circuitry, but they have used seed-driven approaches wherein a circuit of
      interest is defined a priori. This limits their ability to identify network
      abnormalities beyond the prevailing framework. This limitation is particularly
      problematic within the prefrontal cortex (PFC), which is large and heterogeneous
      and where a priori specification of seeds is therefore difficult. A hypothesis
      neutral, data-driven approach to the analysis of connectivity is vital. METHODS:
      We analyzed resting-state functional connectivity data collected at 3T in 27 OCD
      patients and 66 matched control subjects with a recently developed data-driven
      global brain connectivity (GBC) method, both within the PFC and across the whole
      brain. RESULTS: We found clusters of decreased connectivity in the left lateral
      PFC in both whole-brain and PFC-restricted analyses. Increased GBC was found in
      the right putamen and left cerebellar cortex. Within regions of interest in the
      basal ganglia and thalamus, we identified increased GBC in dorsal striatum and
      anterior thalamus, which was reduced in patients on medication. The ventral
      striatum/nucleus accumbens exhibited decreased global connectivity but increased
      connectivity specifically with the ventral anterior cingulate cortex in subjects
      with OCD. CONCLUSIONS: These findings identify previously uncharacterized PFC and
      basal ganglia dysconnectivity in OCD and reveal differentially altered GBC in
      dorsal and ventral striatum. Results highlight complex disturbances in PFC
      networks, which could contribute to disrupted cortical-striatal-cerebellar
      circuits in OCD.

PMID- 24314354
TI  - Effect of health information technology interventions on lipid management in
      clinical practice: a systematic review of randomized controlled trials.
AB  - BACKGROUND: Large gaps in lipid treatment and medication adherence persist in
      high-risk outpatients in the United States. Health information technology (HIT)
      is being applied to close quality gaps in chronic illness care, but its utility
      for lipid management has not been widely studied. OBJECTIVE: To perform a
      qualitative review of the impact of HIT interventions on lipid management
      processes of care (screening or testing; drug initiation, titration or adherence;
      or referrals) or clinical outcomes (percent at low density lipoprotein
      cholesterol goal; absolute lipid levels; absolute risk scores; or cardiac
      hospitalizations) in outpatients with coronary heart disease or at increased
      risk. METHODS: PubMed and Google Scholar databases were searched using Medical
      Subject Headings related to clinical informatics and cholesterol or lipid
      management. English language articles that described a randomized controlled
      design, tested at least one HIT tool in high risk outpatients, and reported at
      least 1 lipid management process measure or clinical outcome, were included.
      RESULTS: Thirty-four studies that enrolled 87,874 persons were identified. Study
      ratings, outcomes, and magnitude of effects varied widely. Twenty-three trials
      reported a significant positive effect from a HIT tool on lipid management, but
      only 14 showed evidence that HIT interventions improve clinical outcomes. There
      was mixed evidence that provider-level computerized decision support improves
      outcomes. There was more evidence in support of patient-level tools that provide
      connectivity to the healthcare system, as well as system-level interventions that
      involve database monitoring and outreach by centralized care teams. CONCLUSION:
      Randomized controlled trials show wide variability in the effects of HIT on lipid
      management outcomes. Evidence suggests that multilevel HIT approaches that target
      not only providers but include patients and systems approaches will be needed to
      improve lipid treatment, adherence and quality.

PMID- 24314355
TI  - An International Atherosclerosis Society Position Paper: global recommendations
      for the management of dyslipidemia.
AB  - An international panel of the International Atherosclerosis Society has developed
      a new set of recommendations for management of dyslipidemia. The panel identifies
      non-high density lipoprotein cholesterol (non-HDL-C) as the major atherogenic
      lipoprotein. Primary and secondary prevention are considered separately. Optimal
      levels for atherogenic lipoproteins are derived for the two forms of prevention.
      For primary prevention, the recommendations emphasize lifestyle therapies to
      reduce atherogenic lipoproteins; drug therapy is reserved for higher risk
      subjects. Risk assessment is based on estimation of lifetime risk according to
      differences in baseline population risk in different nations or regions.
      Secondary prevention emphasizes use of cholesterol-lowering drugs to attain
      optimal levels of atherogenic lipoproteins. 

PMID- 24314356
TI  - Inherited lipemic splenomegaly and the spectrum of apolipoprotein E p.Leu167del
      mutation phenotypic variation.
AB  - OBJECTIVE: We review disorders associated with splenomegaly and dyslipidemia with
      an emphasis on the APOE p.Leu167del mutation. Recent studies suggest that this
      rare mutation may present more often without splenomegaly in patients with
      familial combined hyperlipidemia or autosomal dominant hypercholesterolemia. We
      supplement the literature review by reporting a new kindred. METHODS: We reviewed
      our 3405-patient lipid clinic database to identify persons with dyslipidemia and
      splenomegaly. Identified patients were evaluated for relevant disorders,
      including genetic testing for a 3-base pair deletion in APOE that causes deletion
      of leucine at position 167 of apolipoprotein E. RESULTS: We identified 4 patients
      with splenomegaly and dyslipidemia, one of whom had a heterozygous APOE
      p.Leu167del mutation. This proband is a 76-year-old man with a history of
      splenomegaly first noted at age 13 and subsequent diagnosis of
      hypertriglyceridemia, low high-density lipoprotein cholesterol, leukopenia, and
      thrombocytopenia in his third decade. He never required splenectomy, and his
      splenic enlargement regressed over time with medical management of his
      hypertriglyceridemia. The APOE p.Leu167del mutation was also found in the
      proband's son and granddaughter, neither of whom has splenomegaly or marked
      dyslipidemia. CONCLUSION: Splenomegaly in association with dyslipidemia may
      indicate the presence of an underlying disorder. We discuss possible causes,
      review the literature relating to the rare APOE p.Leu167del mutation, and present
      a 3-generation kindred with variable phenotypic expression of this mutation.
      Severity of expression may depend on genotype, sex, or effective medical
      management of dyslipidemia or a combination of these factors. Aggressive lipid
      treatment may improve or prevent splenomegaly among patients with this disorder.

PMID- 24314357
TI  - Use of health information technology (HIT) to improve statin adherence and low
      density lipoprotein cholesterol goal attainment in high-risk patients:
      proceedings from a workshop.
AB  - The workshop discussions focused on how low-density lipoprotein cholesterol (LDL
      C) goal attainment can be enhanced with the use of health information technology
      (HIT) in different clinical settings. A gap is acknowledged in LDL-C goal
      attainment, but because of the passage of the American Recovery & Reinvestment
      Act and the Health Information Technology for Economic and Clinical Health Acts
      there is now reason for optimism that this gap can be narrowed. For HIT to be
      effectively used to achieve treatment goals, it must be implemented in a setting
      in which the health care team is fully committed to achieving these goals.
      Implementation of HIT alone has not resulted in reducing the gap. It is critical
      to build an effective management strategy into the HIT platform without
      increasing the overall work/time burden on staff. By enhancing communication
      between the health care team and the patient, more timely adjustments to
      treatment plans can be made with greater opportunity for LDL-C goal attainment
      and improved efficiency in the long run. Patients would be encouraged to take a
      more active role. Support tools are available. The National Lipid Association has
      developed a toolkit designed to improve patient compliance and could be modified
      for use in an HIT system. The importance of a collaborative approach between
      nongovernmental organizations such as the National Lipid Association, National
      Quality Forum, HIT partners, and other members of the health care industry offers
      the best opportunity for long-term success and the real possibility that such
      efforts could be applied to other chronic conditions, for example, diabetes and
      hypertension. 

PMID- 24314358
TI  - Resequencing the untranslated regions of the lipoprotein lipase (LPL) gene
      reveals that variants in microRNA target sequences are associated with
      triglyceride levels.
AB  - BACKGROUND: Rare variants in the protein coding regions of the lipoprotein lipase
      (LPL) gene have been shown to be important in the development of
      hypertriglyceridemia. OBJECTIVES: The aim of this study was to determine whether
      rare variants in the 3' and 5' untranslated regions (UTRs) of the LPL gene are
      also associated with severe hypertriglyceridemia. METHODS: The DNA sequences of
      the 3' and 5' UTRs of the LPL gene of 63 patients with triglycerides > 875 mg/dL
      (10 mmol) and 69 probands with triglycerides below the 25th percentile for age
      and sex were determined. The sequence at the 5' end was extended to include 2
      further elements (-702 to -666 and -468 to -430) shown to be associated with the
      control of LPL expression. RESULTS: No statistically significant difference was
      found in the occurrence of rare mutations in either the 3' or the 5' UTRs between
      the 2 groups. Sequence analysis allowed the genotyping of 47 single nucleotide
      polymorphisms (SNPs) in the 3' UTR and 11 in the 5' UTR. Two groups of SNPs in
      the 3' UTR, based on allelic association, were statistically significantly
      associated with plasma triglycerides. Each of these groups contained SNPs in the
      target sequences for microRNAs. These findings were replicated in independently
      formed groups. CONCLUSION: We provide genetic evidence that microRNAs may play a
      role in the expression of LPL and thus plasma triglyceride levels.

PMID- 24314359
TI  - Long-term safety and efficacy of TAK-085 in Japanese subjects with
      hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids
      randomized long-term (ORL) study.
AB  - BACKGROUND: TAK-085 is an omega-3 preparation that contains eicosapentaenoic acid
      ethyl-ester (EPA-E) and docosahexaenoic acid-ethyl ester used in the management
      of hypertriglyceridemia. OBJECTIVE: The aim of the study was to evaluate the long
      term safety (adverse events [AEs], laboratory parameters, vital signs, weight,
      and electrocardiograms) and effects on lipid profiles, especially triglyceride
      levels, of TAK-085 in Japanese patients with hypertriglyceridemia (triglyceride
      levels >=150 mg/dL and <750 mg/dL). METHODS: In this multicenter, open-label,
      randomized study, adults with hypertriglyceridemia undergoing lifestyle
      modification received TAK-085 2 g (2 g once daily; n = 165) or 4 g (2 g twice
      daily; n = 171), or EPA-E 1.8 g (0.6 g three times daily; n = 167) for 52 weeks.
      Patients were stratified for co-administration of a statin. RESULTS: TAK-085 was
      well tolerated throughout the 52-week study. Overall, no substantial differences
      were found in the tolerability of TAK-085 2 g, TAK-085 4 g, and EPA-E 1.8 g with
      incidence rates for AEs of 83.6%, 86.0%, and 89.2%, respectively. Most AEs were
      mild or moderate in severity. Triglyceride levels decreased from baseline in all
      groups by week 4, and the decreases were maintained throughout the study. At week
      52 the reduction in triglycerides with TAK-085 2 g (-13.9%) was similar to that
      with EPA-E 1.8 g (-12.1%), whereas the reduction seen with TAK-085 4 g (-25.5%)
      was greater than that with EPA-E 1.8 g, as assessed by point estimates and 95%
      confidence intervals. CONCLUSIONS: TAK-085 was safe and well tolerated for up to
      52 weeks of treatment in Japanese patients with hypertriglyceridemia undergoing
      lifestyle modification. Reductions in triglyceride levels achieved after 4 weeks
      were maintained at 52 weeks.

PMID- 24314360
TI  - Is the superiority of apoB over non-HDL-C as a marker of cardiovascular risk in
      the INTERHEART study due to confounding by related variables?
AB  - BACKGROUND: Patients with increased numbers of cholesterol-depleted
      apolipoprotein B (apoB) particles frequently have multiple other abnormalities,
      which might confound the comparison of apoB and non-high-density-lipoprotein
      cholesterol (non-HDL-C) as markers of cardiovascular risk. OBJECTIVE: We wanted
      to determine whether the superiority of apoB over non-HDL-C as a marker of
      cardiovascular risk in the INTERHEART study is due to such variables that act as
      confounders of the primary comparison. METHODS: To test for confounding, cases
      and controls were first separated into 3 groups on the basis of the percentile
      levels within the study of non-HDL-C and apoB with discordance defined as a
      difference of 5 percentile points. Logistic regression was used to compute odds
      ratio of myocardial infarction (as an outcome) for different categories, assuming
      concordance as reference adjusted for other confounders. RESULTS: Plasma
      triglyceride and non-HDL-C levels were highest in the discordant group with
      lowest risk and lowest in the discordant group with highest risk, whereas apoB
      was highest in the discordant group with the highest risk and lowest in the
      discordant group with the lowest group. Moreover, no significant change was found
      in the odds ratio for either discordant group when adjusted for the effect of any
      of the variables examined, evidence that none confounded the primary comparison.
      CONCLUSION: Factors such as hypertriglyceridemia do not confound the comparison
      of apoB and non-HDL-C, further evidence that apoB is superior to non-HDL-C as a
      marker of the importance of the apoB atherogenic lipoproteins in cardiovascular
      risk.

PMID- 24314361
TI  - Lowering LDL cholesterol, but not raising LDL receptor activity, by ezetimibe.
AB  - BACKGROUND: Ezetimibe, an inhibitor of intestinal cholesterol absorption, is
      effective in lowering serum low-density lipoprotein (LDL) cholesterol with or
      without coadministration of statin. Ezetimibe-plus-statin therapy enhances LDL
      receptor activity, but it is still unclear whether ezetimibe alone enhances LDL
      receptor activity, resulting in LDL cholesterol decrease. OBJECTIVE: We
      investigated whether ezetimibe lowers serum LDL cholesterol by raising LDL
      receptor activity in humans. METHODS: Patients with hypercholesterolemia (n = 28;
      age [mean +/- SD], 61.6 +/- 13.0 years; 57% men) were treated with ezetimibe (10
      mg/d) for 4 months. Before and after the treatment, serum LDL cholesterol,
      apolipoprotein B (apo B), and apolipoprotein C-II (apo C-II) were measured. LDL
      receptor activities were estimated with the equation we reported previously as
      follows: LDL receptor activity (represented as a percentage of
      normocholesterolemic subjects) = 63.595 + apo C-II (in mg/dL) * 13.459-apo B (in
      mg/dL) * 0.366. RESULTS: By the treatment of ezetimibe, LDL cholesterol (176.8 +/
      17.9 vs 138.0 +/- 19.7 mg/dL) was lowered 21.9% significantly (P < .01). The
      estimated LDL receptor activities before and after the ezetimibe treatment were
      86.8% +/- 21.4% and 89.6% +/- 19.7%, respectively, with no significant difference
      between them (P = .13). CONCLUSION: Ezetimibe lowered LDL cholesterol
      significantly in patients with hypercholesterolemia without raising LDL receptor
      activity. The enhancement of LDL receptor activity is less involved in the
      pharmacologic action of ezetimibe.

PMID- 24314362
TI  - Lipid control in patients with coronary heart disease treated in primary care or
      cardiology clinics.
AB  - BACKGROUND: Guidelines recommend low-density lipoprotein-cholesterol (LDL-C)
      target of <70 mg/dL in patients with coronary disease. However, this goal is not
      achieved in many patients. OBJECTIVES: We compared LDL-C control in patients with
      coronary disease treated by a primary care physician or with the addition of a
      cardiologist. METHODS: Included were patients with coronary disease who had full
      lipid profile. Primary end points included the percentage of patients who
      achieved the LDL-C goals of <100 mg/dL and <70 mg/dL. RESULTS: Of the 27,172
      patients, 12,965 (47.7%) were followed only by a primary care physician and
      14,207 (52.3%) were also followed by a cardiologist. Overall, 18,366 patients
      (67.6%) achieved the LDL-C goal of <100 mg/dL, and 6517 patients (24%) achieved
      the LDL-C goal of <70 mg/dL. Patients followed by a cardiologist more frequently
      achieved the LDL-C goal of <100 mg/dL (74.3% and 60.3%; P < .0001, in patients
      treated by a cardiologist or by a primary care physician, respectively), as well
      as the lower LDL-C goal of <70 mg/dL (27.2% and 20.4%; P < .0001, in patients
      treated by a cardiologist or by a primary care physician, respectively).
      Differences in LDL-C control remained significant after a multivariate
      adjustment. Patients followed by a cardiologist were more commonly treated with
      highly potent statins and with non-statin cholesterol-lowering drugs.
      CONCLUSIONS: Among patients with coronary disease, those followed by a
      cardiologist receive a more aggressive antilipid treatment and more frequently
      achieve lipids goals. Nevertheless, the disappointingly poor lipid control in
      both groups warrants an effort to improve adherence for guidelines in both
      primary care and cardiology clinics.

PMID- 24314363
TI  - Managing to low-density lipoprotein particles compared with low-density
      lipoprotein cholesterol: a cost-effectiveness analysis.
AB  - BACKGROUND: Meta-analyses of clinical trials have shown that using statins to
      lower low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular events,
      and more intensive lowering of LDL-C further decreases the risk of occlusive
      vascular events. Lipoprotein studies suggest treating patients more aggressively
      when low-density lipoprotein particle (LDL-P) number is discordantly high in the
      presence of normal LDL-C levels. Failure to manage LDL-P numbers may lead to
      additional direct and indirect costs. OBJECTIVE: This analysis modeled direct and
      indirect costs associated with cardiovascular events due to suboptimal treatment
      resulting from discordance between LDL-C and LDL-P levels. METHODS: The analysis
      was conducted from the payer perspective and the employer perspective,
      respectively, over a 3-year time period. Clinical data were obtained from the
      Multi-Ethnic Study of Atherosclerosis, a community-based population study. The
      employer perspective included indirect costs and quality-adjusted life years in
      addition to the direct costs and cardiovascular disease events considered in the
      payer analysis. All costs are reported in 2011 dollars. RESULTS: From the payer
      perspective, managing LDL-C and LDL-P in comparison with LDL-C alone reduced
      costs ($21,212) and cardiovascular events (9 events). Similar patterns were
      observed for managing LDL-P alone in comparison with LDL-C. From the employer
      perspective, managing both LDL-P alone or in combination with LDL-C also resulted
      in lower costs, fewer cardiovascular disease events, and increased quality
      adjusted life years in comparison with LDL-C. CONCLUSION: This analysis indicates
      that the benefits of additional testing to optimally manage LDL-P levels outweigh
      the costs of more aggressive treatment. These favorable results depended on the
      cost of drug therapy.

PMID- 24314364
TI  - Dyslipidemia and associated risk factors in a resettlement colony of Delhi.
AB  - BACKGROUND: Cardiovascular diseases are a major cause of morbidity and mortality
      in India, with dyslipidemia contributing significantly to the risk. There are few
      community-based studies that highlight the burden and risk factors associated
      with dyslipidemia in the Indian population. OBJECTIVES: To determine the
      prevalence and risk factors associated with dyslipidemia among adults ages 18
      years and older in a resettlement colony located in central Delhi. METHODS: A
      cross-sectional study that included a random sample of 200 adults was designed. A
      study tool based on the World Health Organization STEPwise approach to
      surveillance of noncommunicable diseases and their risk factors (STEPS)
      questionnaire was used. Fasting venous blood sample was collected to assess the
      lipid profile and anthropometric measures of the participants were recorded.
      Criteria based on the Third Report of the National Cholesterol Education Program
      Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in
      Adults were used to define the cut offs for dyslipidemia. Data were analyzed with
      the Statistical Package for Social Sciences, version 17. RESULTS: Of a total of
      200 study subjects, 34% had increased total cholesterol levels (>=200 mg %), 38%
      had increased low-density lipoprotein levels (>=130 mg %), 40% had increased
      triglyceride levels (>=150 mg %), and 42% had low high-density lipoprotein levels
      (<40 mg %). Using the logistic regression model, we found age, hypertension,
      alcohol consumption, and abdominal obesity to be associated with increased odds
      of dyslipidemia. CONCLUSION: A high proportion of individuals in the community
      have dyslipidemia, often associated with modifiable risk factors. The situation
      demands programs aimed at risk factor reduction. A focus on behavior change and
      health promotion targeting the younger age group is recommended.

PMID- 24314366
TI  - Resequencing the APOE gene reveals that rare mutations are not significant
      contributory factors in the development of type III hyperlipidemia.
AB  - BACKGROUND: APOE (apolipoprotein E gene) 2/2 genotype and an apolipoprotein
      B/total cholesterol (ApoB/TC) ratio <0.15 are diagnostic for type III
      hyperlipidemia. We hypothesized that patients with APOE genotype 2/3 or 2/4 and
      an ApoB/TC ratio <0.15 may have a mutation in their epsilon 3 or 4 allele,
      resulting in a type III hyperlipidemia phenotype. OBJECTIVE: We tested this
      hypothesis. METHODS: The DNA sequence of all 4 exons and exon/intron boundaries
      of the APOE (plus 600 bp upstream of exon 1) of 47 patients with APOE 2/3 and 18
      patients with APOE 2/4 genotype and an ApoB/TC ratio <0.15 was determined. As
      controls the APOE sequence of 53 APOE genotype 2/3 and 20 APOE genotype 2/4
      probands with ApoB/TC ratio >0.15 was determined. The sequence analysis was
      extended to include 47 patients with APOE genotype 3/3, 14 with APOE genotype
      3/4, and 3 with APOE genotype 4/4 and an ApoB/TC ratio <0.15. Finally, we
      determined the sequence of the APOE gene in 145 patients with an ApoB/TC ratio
      >0.15 and who had triglycerides above the 90th percentile for age and sex.
      RESULTS: No deleterious variants in the APOE gene were observed in patients with
      APOE genotype other than 2/2 and an ApoB/TC ratio <0.15. Only a single probably
      deleterious variant, K72E, was observed in patients with triglycerides above the
      90th percentile. CONCLUSIONS: Patients with an ApoB/TC ratio <0.15 do not have an
      increased likelihood of mutation in the APOE gene, and rare variants in the APOE
      gene are not important in the development of hypertriglyceridemia.

PMID- 24314365
TI  - Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma
      of patients with metabolic syndrome.
AB  - BACKGROUND: Obesity-linked metabolic syndrome (MetS) is associated with a
      dyslipidemic profile that includes hypertriglyceridemia and low plasma high
      density lipoprotein (HDL) cholesterol. HDL initiates reverse cholesterol
      transport via macrophage cholesterol efflux (MCE). Some hypothesize that
      dyslipidemic patients have impaired reverse cholesterol transport. MCE to patient
      plasma, a metric of HDL function, inversely correlates with atherosclerotic
      burden. Paradoxically, MCE to plasma of hypertriglyceridemic subjects is higher
      than that to normolipidemic (NL) plasma. OBJECTIVE: Although weight loss reduces
      dyslipidemia, its effect on MCE to the plasma of obese patients with MetS is
      unknown. Thus, we tested the hypothesis that reducing dyslipidemia with weight
      loss reduces the MCE capacity of MetS plasma to that of NL plasma. METHODS:
      Cholesterol efflux (MCE) from THP-1 macrophages to plasma from NL controls and to
      obese patients with MetS before and after weight loss was measured. RESULTS: MCE
      to plasma of obese patients with MetS was higher than that of control plasma (P =
      .006). Weight loss in patients with MetS (mean, -9.77 kg) reduced dyslipidemia,
      insulin resistance, and systolic blood pressure. HDL cholesterol was unchanged,
      and apolipoprotein A-I decreased with weight loss. Weight loss in patients with
      MetS normalized MCE (P < .001) to that of NL subjects. MCE correlated with
      apolipoprotein B levels (r2 = 0.13-0.38). Chromatography showed that macrophage
      cholesterol initially associates with HDL but accumulates in apolipoprotein B
      containing lipoproteins at later times. CONCLUSIONS: Although the initial
      acceptor of MCE is HDL, the elevated apolipoprotein B lipoproteins are a
      cholesterol sink that increases MCE in patients with MetS. Weight loss results in
      decreased apolipoprotein B lipoproteins and decreased MCE to plasma of patients
      with MetS.

PMID- 24314367
TI  - Differences in cholesterol management among states in relation to health
      insurance and race/ethnicity across the United States.
AB  - BACKGROUND: Across the United States, hyperlipidemia remains inadequately
      controlled and may vary across states according to differences in health
      insurance coverage and/or race/ethnicity. OBJECTIVE: To examine relationships
      between states' health insurance and race/ethnicity characteristics with measures
      of hyperlipidemia management across the 50 U.S. states and the District of
      Columbia. METHODS: Cross-validated, multiple linear regression modeling was used
      to analyze associations between states' health insurance patterns or proportions
      of racial minorities (from the 2010 U.S. Census data) and states' aggregate
      frequency of checking cholesterol within the previous 5 years or prescriptions
      written for lipid-lowering medications (from national survey and population
      adjusted retail prescription data, respectively), with adjustments for age, sex,
      body mass index, race/ethnicity, and poverty. RESULTS: In states with
      proportionately more uninsured, cholesterol levels are checked less often, but in
      states with proportionately more private, Medicare, or Medicaid coverage,
      providers are not necessarily more likely to check cholesterol or to write more
      prescriptions. In states with proportionately more African-Americans and/or
      Hispanics, cholesterol is more likely to be checked, but in states with more
      African-Americans, more prescriptions were written, whereas in states with more
      Hispanics, fewer statin prescriptions were written. CONCLUSION: Variations across
      states in insurance and racial/ethnicity mix are associated with variations in
      hyperlipidemia management; less-insured states may be less effective whereas
      states with more private, Medicare, or Medicaid coverage may not be more
      effective. In states with proportionately more African-Americans vs. Hispanics,
      lipid medications may be prescribed differently. Our findings warrant further
      investigations.

PMID- 24314368
TI  - Delayed diagnosis of familial hypercholesterolemia: a case report of two patients
      from Egypt.
AB  - Two young Egyptian women with homozygous familial hypercholesterolemia (HoFH)
      were diagnosed after the appearance of vascular complications despite the
      presence of family history and suggestive clinical features. The first patient
      was treated by repeated surgical excisions of disfiguring tendon xanthomas
      diagnosed as "lipomas". The second patient, presenting with embolic ischemia, had
      an amputation of the forearm and repeated reconstructive surgical procedures.
      Each patient was diagnosed as HoFH after presenting with typical angina to a
      cardiologist. The first patient had severe aortic stenosis, left main and multi
      vessel coronary artery disease, and died at age 21 years. The second patient had
      multivessel coronary artery disease that was treated by Percutaneous Coronary
      Intervention (PCI) with drug-eluting stents. These cases demonstrate that the
      delayed diagnosis of xanthomas and familial inheritance characteristic of HoFH
      leads to atherosclerosis and aortic stenosis early in life. 

PMID- 24314369
TI  - iPhone apps for heterozygous familial hypercholesterolemia.

PMID- 24314370
TI  - Efficient transmission of cassava brown streak disease viral pathogens by chip
      bud grafting.
AB  - BACKGROUND: Techniques to study plant viral diseases under controlled growth
      conditions are required to fully understand their biology and investigate host
      resistance. Cassava brown streak disease (CBSD) presents a major threat to
      cassava production in East Africa. No infectious clones of the causal viruses,
      Cassava brown streak virus (CBSV) or Ugandan cassava brown streak virus (UCBSV)
      are available, and mechanical transmission to cassava is not effective. An
      improved method for transmission of the viruses, both singly and as co-infections
      has been developed using bud grafts. FINDINGS: Axillary buds from CBSD
      symptomatic plants infected with virulent isolates of CBSV and UCBSV were excised
      and grafted onto 6-8 week old greenhouse-grown, disease-free cassava plants of
      cultivars Ebwanateraka, TME204 and 60444. Plants were assessed visually for
      development of CBSD symptoms and by RT-PCR for presence of the viruses in leaf
      and storage root tissues. Across replicated experiments, 70-100% of plants
      inoculated with CBSV developed CBSD leaf and stem symptoms 2-6 weeks after bud
      grafting. Infected plants showed typical, severe necrotic lesions in storage
      roots at harvest 12-14 weeks after graft inoculation. Sequential grafting of buds
      from plants infected with UCBSV followed 10-14 days later by buds carrying CBSV,
      onto the same test plant, resulted in 100% of the rootstocks becoming co-infected
      with both pathogens. This dual transmission rate was greater than that achieved
      by simultaneous grafting with UCBSV and CBSV (67%), or when grafting first with
      CBSV followed by UCBSV (17%). CONCLUSIONS: The bud grafting method described
      presents an improved tool for screening cassava germplasm for resistance to CBSD
      causal viruses, and for studying pathogenicity of this important disease. Bud
      grafting provides new opportunities compared to previously reported top and side
      grafting systems. Test plants can be inoculated as young, uniform plants of a
      size easily handled in a small greenhouse or large growth chamber and can be
      inoculated in a controlled manner with CBSV and UCBSV, either singly or together.
      Disease symptoms develop rapidly, allowing better studies of interactions between
      these viral pathogens, their movement within shoot and root systems, and how they
      induce their destructive disease symptoms.

PMID- 24314372
TI  - Red face revisited: I.

PMID- 24314371
TI  - Ecological relevance of Sentinels' biomarker responses: a multi-level approach.
AB  - In response to the need for more sensitive and rapid indicators of environmental
      quality, sublethal effects on the lowest levels of biological organization have
      been investigated. The ecological relevance of these responses assumes a
      prevailing role to assure effectiveness as indicator of ecological status. This
      study aimed to investigate the linkages between biomarker responses of caged
      bivalves and descriptive parameters of macrobenthic community structure. For this
      purpose a multi-level environmental assessment of marine and estuarine zones was
      performed in Sao Paulo coast, Brazil. Multivariate analysis was applied to
      identify linkages between biological responses and ecological indices, as well as
      to characterizing the studied stations. Individuals of the marine mussel Perna
      perna caged along Santos Bay showed signs of oxidative stress, lysosomal membrane
      destabilization, histological alterations and reduced embryonic development. The
      estuarine oyster Crassostrea rhizophorae caged along Santos Port Channel showed
      alterations on biotransformation enzymes and antioxidant system, DNA damage and
      lysosomal membrane destabilization. The benthic community analysis showed reduced
      richness and diversity in the same areas of the Santos bay and estuary where
      biomarker responses were altered. Our results revealed that xenobiotics are
      inducing physiological stress, which may lead to changes of the benthic community
      structure and deterioration of the ecological status over time. Integrating
      biomarker responses and ecological indexes improved certainty that alterations
      found at community level could be related to xenobiotic as stressors, which was
      very useful to improve the discriminatory power of the environmental assessment. 

PMID- 24314373
TI  - Basic histological structure and functions of facial skin.
AB  - The skin and its appendages that derive from the epidermis (hair follicles, sweat
      glands, sebaceous glands, nails, and mammary glands) establish the integumentary
      system. Histologically, skin has two main layers-the epidermis and the dermis
      with a subcutaneous fascia called the hypodermis, which lies deep in the dermis.
      The epidermis is formed of four to five layers of cells made mostly out of
      keratinocytes, along with three other different and less abundant cells. The
      dermis underlies the epidermis. The hypodermis is a looser connective tissue that
      is located beneath the dermis. It blends to the dermis with an unclear boundary. 

PMID- 24314374
TI  - Facial anatomy.
AB  - Dermatologic problems of the face affect both function and aesthetics, which are
      based on complex anatomical features. Treating dermatologic problems while
      preserving the aesthetics and functions of the face requires knowledge of normal
      anatomy. When performing successfully invasive procedures of the face, it is
      essential to understand its underlying topographic anatomy. This chapter presents
      the anatomy of the facial musculature and neurovascular structures in a
      systematic way with some clinically important aspects. We describe the
      attachments of the mimetic and masticatory muscles and emphasize their functions
      and nerve supply. We highlight clinically relevant facial topographic anatomy by
      explaining the course and location of the sensory and motor nerves of the face
      and facial vasculature with their relations. Additionally, this chapter reviews
      the recent nomenclature of the branching pattern of the facial artery. 

PMID- 24314375
TI  - Acneiform eruptions.
AB  - Is it acne or is it not? When this question arises, we can presume that we have
      crossed the boundaries of "acneiform eruptions" of the face. Although acne may be
      considered a condition fairly easy to diagnose, it is not rare for the practicing
      dermatologist or the general physician to wonder when faced with an acneiform
      eruption before establishing a diagnosis. In this review, we address facial
      acneiform eruptions in children and in adults, including perioral dermatitis,
      granulomatous periorificial dermatitis, nevus comedonicus, acne cosmetica,
      rosacea, demodicosis, folliculitis, acneiform presentation of cutaneous
      lymphomas, and drug-induced [epidermal growth factor receptor (EGFR) inhibitors,
      steroids, etc.] acneiform eruptions, along with their diagnosis and therapeutic
      approaches. The major distinguishing factor in acneiform eruptions is that, in
      contrast to acne, there are no comedones (whiteheads or blackheads).

PMID- 24314376
TI  - Rosacea and rhinophyma.
AB  - Rosacea is a common and chronic inflammatory cutaneous disease with unknown
      etiology. The pathophysiology of rosacea is still poorly understood.
      Epidemiological studies indicate a genetic component, but a rosacea gene has not
      been detected yet. Recent molecular studies propose that an altered innate immune
      response is involved in the pathogenesis of the rosacea disease. Signs of rosacea
      are indicated by the presence of characteristic facial or ocular inflammation
      involving both the vascular and tissue stroma. A wide range of drug options is
      available for the treatment of rosacea, including several topical ones
      (metronidazole, antibiotics, azelaic acid, benzoyl peroxide,
      sulfacetamide/sulfur, retinoids) and oral ones (mainly tetracyclines,
      metronidazole, macrolides, isotretinoin). This review highlights the recent
      clinical and pathophysiological developments concerning rosacea. 

PMID- 24314377
TI  - Granulomatous disorders.
AB  - Almost all granulomatous skin disorders can cause red lesions on the face. Such
      disorders may include many bacterial, fungal, or parasitic infections,
      noninfectious inflammatory disorders, foreign body reactions, and even neoplasms.
      Clinically, they usually present with papules, plaques, nodules, and/or
      abscesses, which may ulcerate. It may be helpful in their differential diagnosis
      to define certain clinical patterns, such as multiple and discrete papules,
      necrotic or umbilicated papules or nodules, annular plaques, vegetative plaques
      or tumors, verrucous plaques or tumors, abscesses and/or sinuses, and
      lymphocutaneous pattern. Some disorders, such as sarcoidosis, can cause a wide
      variety of lesions. We accept that cutaneous leishmaniasis is also among such
      great imitators. 

PMID- 24314378
TI  - Pigmentation disorders: hyperpigmentation and hypopigmentation.
AB  - Pigmentation disorders include a large number of heterogeneous conditions that
      are usually characterized by altered melanocyte density, melanin concentration,
      or both, and result in altered pigmentation of the skin. Some of these disorders
      are extremely common (melasma, vitiligo), whereas others are rare. In this
      contribution, we review the most common pigmentation disorders that appear on the
      face. These lesions, even though mostly asymptomatic, have a great impact on a
      patient's quality of life. 

PMID- 24314379
TI  - Photodermatoses, including phototoxic and photoallergic reactions (internal and
      external).
AB  - Photodermatoses are caused by an abnormal reaction mainly to the ultraviolet
      component of sunlight. Photodermatoses can be broadly classified into four
      groups: immunologically mediated photodermatoses, chemical- and drug-induced
      photosensitivity, photoaggravated dermatoses, and DNA repair-deficiency
      photodermatoses. In this review, we focus mainly on chemical- and drug-induced
      photosensitivity, namely, phototoxicity and photoallergy. 

PMID- 24314381
TI  - Flat pigmented macules on sun-damaged skin of the head/neck: junctional nevus,
      atypical lentiginous nevus, or melanoma in situ?
AB  - The clinical recognition of lentigo maligna (LM) in the mottled chronic sun
      damaged skin can be challenging, because it shares many clinical features with
      other pigmented macules that commonly arise on sun-damaged skin. These include
      solar lentigo, flat seborrheic keratosis, and pigmented actinic keratosis, but
      almost never "nevus." The reason nevus is not included in the differential
      diagnosis of LM can be explained by the fact that the stereotypical appearance of
      a facial nevus differs remarkably from that of an LM. Facial nevi in adults are
      usually nodular, dome-shaped, well-defined, and hypopigmented (i.e., intradermal
      nevus of the Miescher type), whereas LM typically appears as a flat, ill-defined,
      and pigmented macule. Although this concept based on clinical observations sounds
      reasonable, clinicians apply it often only unconsciously and accept a given
      histopathologic diagnosis of a "junctional or lentiginous nevus" of a flat
      pigmented facial macule without the necessary criticism about its
      clinicopathologic validity.

PMID- 24314380
TI  - Morphologic grading and treatment of facial actinic keratosis.
AB  - Actinic keratoses (AKs) represent the earliest stage in the development of
      squamous cell carcinoma (SCC) and represent important biomarkers for individuals
      at risk for development of invasive SCC. Based on clinical morphology, AK can be
      subdivided into three different grades, which correspond to specific
      dermatoscopic, reflectance confocal microscopic, and histopathologic substrates.
      Given the risk for potential progression toward invasive SCC, AK should be
      treated at the earliest stage. A wide range of minimal destructive or topical
      therapies is available for the treatment of AK. The choice of treatment depends
      on the number, size, clinical grading, duration, and location of lesions,
      patient's compliance, general health conditions, and cosmetic outcome. Treatment
      can be divided into lesion-directed and field-directed therapies. Lesion-directed
      treatment focuses on the treatment of single lesions, whereas field-directed
      treatment aims to eliminate both clinically visible and subclinical lesions
      within the field of actinic damage (concept of field cancerization). Noninvasive
      techniques such as dermoscopy and reflectance confocal microscopy can be helpful
      in identifying AK potentially progressing toward SCC, as well as in the selection
      of the adequate treatment and monitoring of the treatment outcome. 

PMID- 24314382
TI  - Diagnosis and management of facial pigmented macules.
AB  - The differential diagnosis of pigmented macules on the mottled chronic sun
      damaged skin of the face is challenging and includes lentigo maligna (LM),
      pigmented actinic (solar) keratosis, solar lentigo, and lichen-planus-like
      keratosis. Although dermatoscopy improves the diagnostic accuracy of the unaided
      eye, the accurate diagnosis and management of pigmented facial macules remains
      one of the most challenging scenarios in daily practice. This is related to the
      fact that pigmented actinic (solar) keratosis, lichen-planus-like keratosis, and
      LM may reveal overlapping criteria, making their differential diagnosis
      clinically difficult. For this reason, practical rules have been introduced,
      which should help to minimize the risk for inappropriate diagnosis and management
      of LM. 

PMID- 24314383
TI  - Lymphocytic infiltrations of face.
AB  - The immune system protects our organism and, of course, our skin from harmful
      factors. One of the key elements of the immune system is lymphocytes. Lymphocytes
      play a role in the pathogenesis of various skin diseases. Lymphocytic infiltrates
      are seen in many skin diseases. Some of the skin diseases characterized by
      lymphocytic infiltration show up in specific anatomic locations, whereas other
      entities can be placed in all areas of the body. The course of lymphocytic
      infiltrations of the face is variable and unpredictable, most often lasting from
      months to years. The most important diseases with lymphocytic infiltration of the
      face are pseudolymphomas. This review discusses various types of cutaneous
      pseudolymphomas and other diseases with lymphocytic infiltration mainly involving
      the face. 

PMID- 24314384
TI  - Red face revisited: Endogenous dermatitis in the form of atopic dermatitis and
      seborrheic dermatitis.
AB  - Atopic dermatitis and seborrheic dermatitis are multifactorial dermatitides that
      are known collectively as endogenous dermatitis. Both conditions can affect the
      face, but they have clinical, epidemiological, and physiopathological
      peculiarities that distinguish them from each other. These two diseases are very
      common all around the world. Atopic dermatitis is associated with xerosis and
      increased susceptibility to irritants and proteins; patients with this condition
      have a tendency to develop asthma, allergic rhinitis, and systemic manifestations
      that are mediated by immunoglobulin E. Seborrheic dermatitis is a moderate
      chronic dermatitis that is restricted to regions with a high production of sebum
      and areas that have cutaneous folds. There are many studies about pathophysiology
      related to the immunology and genetics of atopic dermatitis, but little is known
      about the genetic and immunological markers of seborrheic dermatitis. 

PMID- 24314385
TI  - Contact dermatitis: allergic and irritant.
AB  - Facial contact dermatitis is frequently encountered in medical practice in both
      male and female patients. Identifying the underlying cause can be challenging,
      and the causative agent may be overlooked if it is not considered during the
      assessment of a patient. The two main types of contact dermatitis are irritant
      contact dermatitis (ICD) and allergic contact dermatitis (ACD). The mechanisms
      and common causative agents vary for both ICD and ACD, but the clinical picture
      is often similar, particularly for chronic disease. Facial contact dermatitis can
      be successfully treated by avoiding the causative agent. In this review, we focus
      on the clinical assessment of a patient with facial contact dermatitis and the
      mechanisms of both ICD and ACD. Common causative agents, including emerging
      allergens, are discussed in detail, and suggestions are made regarding the
      management of patients with proven ICD or ACD of the face. 

PMID- 24314386
TI  - Perioral dermatitis.
AB  - Perioral dermatitis is a relatively common inflammatory facial skin disorder that
      predominantly affects women. It is rarely diagnosed in children. A typical
      perioral dermatitis presentation involves the eruption of papules and pustules
      that may recur over weeks to months, occasionally with fine scales. The
      differential diagnosis includes seborrheic dermatitis, systemic lupus
      erythematosus, acne vulgaris, lupus miliaris disseminatus faciei, polymorphous
      light eruption, steroid-induced rosacea, granulomatous perioral dermatitis,
      contact dermatitis (allergic and irritant), and even basal cell carcinoma. The
      histopathology is similar to that of rosacea, with a perivascular and
      perifollicular lymphohistiocytic infiltrate and sebaceous hyperplasia. The
      etiology of perioral dermatitis is unknown, but the uncritical use of topical
      corticosteroids often precedes skin lesions. Physical sunscreens with high sun
      protection factors may cause perioral dermatitis in children. 

PMID- 24314387
TI  - Periorbital (eyelid) dermatides.
AB  - Physicians in various specialties-and dermatologists in particular-frequently
      encounter various forms of inflammation of the eyelids and of the anterior
      surface of the eye. Distinguishing the cause of itchy, painful, red, edematous
      eyelids is often difficult. Because the uppermost layer of the eyelids is part of
      the skin that wraps the entire body, almost every skin disease in the textbook
      can affect the periorbital area as well. In this contribution, we focused on the
      most common such disorders that require special consideration, as a result of
      their special appearance, their challenging diagnosis, or the nature of their
      treatment. We reviewed the key features of several common dermatides that affect
      the eyelids, such as atopic dermatitis, seborrheic dermatitis, allergic contact
      dermatitis, airborne contact dermatitis, rosacea, psoriasis, and others. We
      focused on the special clinical features, causes, and treatments specific to the
      delicate skin of the eyelids. Because structures of the eye itself (i.e., the
      conjunctiva, the cornea, the lens, and the retina) may be involved in some of the
      discussed periorbital skin diseases, we found it useful to add a brief summary of
      the eyelid complications of those diseases. We then briefly reviewed some acute
      sight-threatening and even life-threatening infections of the eyelids, although
      dermatologists are not likely to be the primary care physicians responsible for
      treating them.

PMID- 24314388
TI  - Dermatologic diseases of the external ear.
AB  - The external ear is composed of the auricle (pinna) and the external auditory
      canal. Both of these structures contain elastic cartilage (except the earlobe)
      and a small amount of subcutaneous fat, which are covered by skin. The skin of
      the cartilaginous canal contains hair cells, sebaceous (lipid-producing) glands,
      and apocrine (ceruminous) glands; this is in contrast with the osseous canal,
      which contains neither glands nor hair follicles. The auricle is susceptible to
      environmental influences and trauma. Due to its exposed locale, the ear is
      particularly vulnerable to the effects of ultraviolet light and, consequently, to
      preneoplastic and neoplastic skin lesions. The ear also has a sound-receiving
      function and a location that is both visible and aesthetically obvious, thereby
      drawing considerable attention from the patient. Dermatologic diseases on the
      external ear are seen in a variety of medical disciplines. Dermatologists,
      otorhinolaryngologists, family practitioners, and general and plastic surgeons
      are regularly consulted about cutaneous lesions on the ear. These lesions can be
      grouped into three main categories: (1) infectious; (2) tumoral; and (3)
      noninfectious inflammatory. The purposes of this contribution are to review
      various dermatologic diseases of the external ear and to update current diagnosis
      and treatment information related to these conditions. 

PMID- 24314389
TI  - The red face revisited: connective tissue disorders.
AB  - Red face is not a rare finding in patients with connective tissue disorders. The
      malar eruption is the most frequent cutaneous manifestation of systemic lupus
      erythematosus (LE). This condition is more apparent among fair-skinned
      individuals, and it usually appears after sun exposure. A very important clinical
      sign is that nasolabial folds remain free of any erythematous or other changes.
      With subacute cutaneous LE, sun exposure can provoke a red face that resembles
      the malar eruption of systemic LE. The typical clinical findings of chronic
      cutaneous LE are the discoid lesions. There is a clinical form of chronic
      cutaneous LE called erythema perstans faciei. This form is purely erythematous,
      and it usually appears on the face. Other rare "red face" forms of chronic
      cutaneous LE are LE tumidus and LE telangiectaticus. Red face is not typical of
      systemic sclerosis, but facial telangiectasias are frequent, especially with
      CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and
      telangiectasia) syndrome. The differential diagnoses of other red face
      manifestations are easy due to the additional findings. Telangiectasias are
      accompanied by calcinosis, sclerodactyly, digital ischemia, and Raynaud disease.
      Many studies mention telangiectasias as markers of the severity of the systemic
      sclerosis, the disease duration, any pulmonary arterial hypertension, and any
      esophageal involvement. Purple- or violet-colored upper eyelids are the hallmark
      and one of the first clinical signs that is helpful for the diagnosis of
      dermatomyositis. This violaceous to dusky erythema can extend over the whole face
      and the upper aspects of the trunk. Erythematous changes on the face that are
      different from those of the heliotrope sign which occurs with dermatomyositis may
      be observed in both sun-exposed skin and non-sun-exposed skin. Malar and facial
      erythema, linear extensor erythema, V-sign or shawl sign, and other
      photodistributed eruptions can also appear. 

PMID- 24314390
TI  - Premedicated humor: jest for the health of it.

PMID- 24314391
TI  - History, dermatology, and medicine: another outlook.
AB  - The History of Medicine and of Dermatology tends to analyze what happened in
      these disciplines in a given time and place. Contributions of relevant leaders
      are studied carefully, and their appropriate value to knowledge is determined.
      This is fundamental to understanding present knowledge and what might be expected
      in the future. There is, yet, an additional perspective, namely, the
      relationships between the above and historical phenomena in their wider sense;
      particularly, the correlation between politics, economy, psychohistory, and
      medicine. Evolution of medical knowledge does not occur in a vacuum. This
      contribution provides examples of this viewpoint and how knowledge of history
      makes clearer the development of medicine and vice versa. Emphasis is also made
      on the history and development of dermatology, but rather as an illustration of
      the overall philosophical point of view of the writer than as an analysis of the
      history of dermatology in itself. One may summarize metaphorically this viewpoint
      by stating that while the microscope and the dermatoscope are very important, the
      telescope is vital for integral knowledge. 

PMID- 24314392
TI  - Streptozotocin-induced diabetes in rats diminishes the size of the
      osteoprogenitor pool in bone marrow.
AB  - AIMS: Bone formation is reduced in animals and humans with type 1 diabetes,
      leading to lower bone mass and inferior osseous healing. Since bone formation
      greatly depends on the recruitment of osteoblasts from their bone marrow
      precursors, we tested whether experimental type 1 diabetes in rats diminishes the
      number of bone marrow osteoprogenitors. METHODS: Diabetes was induced by 65 mg/kg
      streptozotocin and after 4 weeks, femoral bone marrow cells were extracted and
      cultured. Tibia and femur were frozen for further analysis. RESULTS: The size of
      the osteoprogenitor pool in bone marrow of diabetic rats was significantly
      reduced, as evidenced by (1) lower (~35 %) fraction of adherent stromal cells (at
      24h of culture); (2) lower (20-25%) alkaline phosphatase activity at 10 days of
      culture; and (3) lower (~40 %) mineralized nodule formation at 21 days of
      culture. Administration of insulin to hyperglycemic rats normalized glycemia and
      abrogated most of the decline in ex vivo mineralized nodule formation. Apoptotic
      cells in tibial bone marrow were more numerous in hyperglycemic rats. Also, the
      levels of malondialdehyde (indicator of oxidative stress) were significantly
      elevated in bone marrow of diabetic animals. CONCLUSIONS: Experimental type 1
      diabetes diminishes the osteoprogenitor population in bone marrow, possibly due
      to increased apoptosis via Oxidative Stress. Reduced number of osteoprogenitors
      is likely to impair osteoblastogenesis, bone formation, and bone healing in
      diabetic animals.

PMID- 24314393
TI  - A comparative study of pigeons and chickens experimentally infected with PPMV-1
      to determine antigenic relationships between PPMV-1 and NDV strains.
AB  - To compare the pathogenicity of PPMV-1 in pigeons and chickens, both species of
      birds were experimentally infected with strain pi/CH/LHLJ/110822, which was
      isolated from a pigeon in China. The clinical signs, gross lesions, and
      histopathological changes were observed in pigeons inoculated with
      pi/CH/LHLJ/110822. The morbidity and mortality rates were 80% and 70% in pigeons,
      respectively, whereas there were no clinical signs or gross lesions in chickens
      inoculated with the same strain. The viral loads in tissue samples were detected
      by real-time RT-PCR, indicating that six tissue samples (i.e., kidney, lung,
      brain, trachea, Harderian glands, and proventriculus) had detectable viral RNA in
      all dead pigeons, and significant differences in viral loads between pigeons and
      chickens were observed in several tissue samples (i.e., Harderian glands,
      proventriculus, duodenum, pancreas, small intestine, and large intestine) on 3
      days post-inoculation (dpi) and in brain tissue on 7 dpi. In general, viral loads
      in pigeons were higher than those in chickens, whereas antibody titers in pigeons
      were lower than those in chickens. These results showed differences in
      pathogenicity, efficiency of viral RNA replication, and humoral immunity,
      indicating different susceptibilities between the host species. Additionally, the
      cross hemagglutination inhibition assay and cross virus neutralization tests
      demonstrated that pi/CH/LHLJ/110822 antigenicity was different from those of
      strains La Sota and F48E9. 

PMID- 24314394
TI  - Sulfonamide inhibition studies of the delta-carbonic anhydrase from the diatom
      Thalassiosira weissflogii.
AB  - The delta-carbonic anhydrase (CA, EC 4.2.1.1) TweCA from the marine diatom
      Thalassiosira weissflogii has recently been cloned, purified and its
      activity/inhibition with anions investigated. Here we report the first
      sulfonamide/sulfamate inhibition study of a delta-class CA. Among the 40 such
      compounds investigated so far, 3-bromosulfanilamide, acetazolamide,
      ethoxzolamide, dorzolamide and brinzolamide were the most effective TweCA
      inhibitors detected, with KIs of 49.6-118nM. Many simple aromatic sulfonamides as
      well as dichlorophenamide, benzolamide, topiramate, zonisamide, indisulam and
      valdecoxib were medium potency inhibitors, (KIs of 375-897nM). Saccharin and
      hydrochlorothiazide were ineffective inhibitors of the delta-class enzyme, with
      KIs of 4.27-9.20MUM. The inhibition profile of the delta-CA is very different
      from that of alpha-, beta- and gamma-CAs from different organisms. Although no X
      ray crystal structure of this enzyme is available, we hypothesize that as for
      other CA classes, the sulfonamides inhibit the enzymatic activity by binding to
      the Zn(II) ion from the delta-CA active site. 

PMID- 24314395
TI  - Triazino indole-quinoline hybrid: a novel approach to antileishmanial agents.
AB  - A novel series of 1,2,4-triazino-[5,6b]indole-3-thione covalently linked to 7
      chloro-4-aminoquinoline have been synthesized and evaluated for their in vitro
      activity against extracellular promastigote and intracellular amastigote form of
      Leishmania donovani. Among all tested compounds, compounds 7a and 7b were found
      to be the most active with IC50 values 1.11, 0.36MUM and selectivity index (SI)
      values 67, >1111, respectively, against amastigote form of L. donovani which is
      several folds more potent than the standard drugs, miltefosine (IC50=8.10MUM,
      SI=7) and sodium stibo-gluconate (IC50=54.60MUM, SI?7). 

PMID- 24314396
TI  - New anti-inflammatory cembranoid diterpenoids from the Vietnamese soft coral
      Lobophytum crassum.
AB  - Four new cembranoid diterpenes lobocrasols A-D (1-4), were isolated from the
      methanol extract of the soft coral Lobophytum crassum. Their structures were
      elucidated by spectroscopic analysis and by comparison of the spectroscopic data
      with those of similar compounds previously reported in literature. The anti
      inflammatory effects of isolated compounds were evaluated using NF-kappaB
      luciferase and reverse transcription polymerase chain reaction (RT-PCR).
      Compounds 1 and 2 significantly inhibited TNFalpha-induced NF-kappaB
      transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50
      values of 6.30+/-0.42 and 6.63+/-0.11MUM, respectively. Furthermore, the
      transcriptional inhibition of these compounds was confirmed by a decrease in
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene
      expression levels in HepG2 cells. 

PMID- 24314397
TI  - Inhibition of serine and proline racemases by substrate-product analogues.
AB  - d-Amino acids can play important roles as specific biosynthetic building blocks
      required by organisms or act as regulatory molecules. Consequently, amino acid
      racemases that catalyze the formation of d-amino acids are potential therapeutic
      targets. Serine racemase catalyzes the reversible formation of d-serine (a
      modulator of neurotransmission) from l-serine, while proline racemase (an
      essential enzymatic and mitogenic protein in trypanosomes) catalyzes the
      reversible conversion of l-proline to d-proline. We show the substrate-product
      analogue alpha-(hydroxymethyl)serine is a modest, linear mixed-type inhibitor of
      serine racemase from Schizosaccharomyces pombe (Ki=167+/-21mM, Ki'=661+/-81mM,
      cf. Km=19+/-2mM). The bicyclic substrate-product analogue of proline, 7
      azabicyclo[2.2.1]heptan-7-ium-1-carboxylate is a weak inhibitor of proline
      racemase from Clostridium sticklandii, giving only 29% inhibition at 142.5mM.
      However, the more flexible bicyclic substrate-product analogue tetrahydro-1H
      pyrrolizine-7a(5H)-carboxylate is a noncompetitive inhibitor of proline racemase
      from C. sticklandii (Ki=111+/-15mM, cf. Km=5.7+/-0.5mM). These results suggest
      that substrate-product analogue inhibitors of racemases may only be effective
      when the active site is capacious and/or plastic, or when the inhibitor is
      sufficiently flexible. 

PMID- 24314398
TI  - Getting to zero HIV deaths: progress, challenges and ways forward.

PMID- 24314399
TI  - Challenges to an effective response for addressing stigma and discrimination
      related to HIV: from denial of rights to construction of support networks.

PMID- 24314400
TI  - Ending the pandemic: reducing new HIV infections to zero.

PMID- 24314402
TI  - Practice patterns of Canadian Ophthalmological Society members in cataract
      surgery--survey 2013.

PMID- 24314401
TI  - In randomization we trust? There are overlooked problems in experimenting with
      people in behavioral intervention trials.
AB  - OBJECTIVES: Behavioral intervention trials may be susceptible to poorly
      understood forms of bias stemming from research participation. This article
      considers how assessment and other prerandomization research activities may
      introduce bias that is not fully prevented by randomization. STUDY DESIGN AND
      SETTING: This is a hypothesis-generating discussion article. RESULTS: An
      additivity assumption underlying conventional thinking in trial design and
      analysis is problematic in behavioral intervention trials. Postrandomization
      sources of bias are somewhat better known within the clinical epidemiological and
      trials literatures. Neglect of attention to possible research participation
      effects means that unintended participant behavior change stemming from artifacts
      of the research process has unknown potential to bias estimates of behavioral
      intervention effects. CONCLUSION: Studies are needed to evaluate how research
      participation effects are introduced, and we make suggestions for how research in
      this area may be taken forward, including how these issues may be addressed in
      the design and conduct of trials. It is proposed that attention to possible
      research participation effects can improve the design of trials evaluating
      behavioral and other interventions and inform the interpretation of existing
      evidence.

PMID- 24314403
TI  - Barriers to accessing low-vision care: the patient's perspective.
AB  - OBJECTIVE: To review the literature regarding barriers that hinder access to low
      vision (LV) care from the perspective of individuals with vision impairment.
      DESIGN: Literature review. METHODS: PubMed and Scopus were used to identify
      relevant cross-sectional studies of awareness of, and barriers to, LV
      rehabilitation. Studies were included if they met the following criteria: (i)
      year of publication within the past 20 years (between 1992 and 2012), and (ii)
      participants of the study included individuals with vision impairment. Fourteen
      studies met the criteria for inclusion and were included in this review. RESULTS:
      Barriers to accessing low-vision service (LVS), from the perspective of
      individuals with vision impairment, included the following: misconceptions of
      LVSs, miscommunication by eye care professionals, lack of awareness, location and
      transportation, the need to appear independent, negative societal views,
      influence of family and friends, insufficient visual impairment to warrant
      services, cost of LVS, and reduced perception of vision loss relative to other
      losses in life. Other factors that were associated with lower use of LVS included
      income level, comorbidities, and education level. CONCLUSIONS: The reasons for
      not accessing LV rehabilitation are complex, and some may be more easily
      addressed than others. A heightened awareness of LV rehabilitation may be
      achieved with better communication by eye care professionals and with public
      education. The stigma associated with the usage of LV aids and admitting a
      disability still seems to exist, but may be reduced by increasing societal
      understanding of LV.

PMID- 24314404
TI  - Overcoming barriers to low-vision rehabilitation services: improving the
      continuum of care.
AB  - OBJECTIVE: Low-vision rehabilitation is beneficial for patients with
      uncorrectable vision impairment, specifically in tasks such as reading and
      activities of daily living. However, referral to and use of these services remain
      less than optimal. Inspired by the findings of the Montreal Barriers Study, this
      article reports on an alternative way of introducing low-vision rehabilitation to
      clients within an ophthalmology department through the presence of an
      optometrist. DESIGN: The Department of Ophthalmology at the Jewish General
      Hospital and the 2 Montreal low-vision rehabilitation agencies established a
      shared satellite office within the department to overcome administrative
      barriers, reduce the need for travel, and provide services within a familiar
      environment for patients. PARTICIPANTS: From June 2011 to December 2012, 35
      patients with low vision were seen by 1 of the optometrists within the
      ophthalmology department. METHODS: The optometrist was available on a part-time
      basis for a total of 20 half days. RESULTS: Seven patients (20%) were already
      clients of a rehabilitation agency and were seen for follow-up, whereas 3 (9%)
      did not qualify for rehabilitation based on their level of visual function. A
      further 6 patients (17%) were treated whereby their needs were met within that
      appointment, and 19 clients (54%) received initial examination and were referred
      to the rehabilitation agency for additional services. CONCLUSIONS: The presence
      of a vision rehabilitation agency in an ophthalmology department through its
      optometrists helps triage patients, increases the integration of this service,
      and facilitates the continuum of care. Further fine-tuning will focus on
      increasing staff awareness and expansion of assistive technologies available at
      the satellite office.

PMID- 24314405
TI  - Histology of Muller's muscle observed in quiescent Graves' orbitopathy.
AB  - OBJECTIVE: Histologic examination of Muller's muscle (MM) in patients with
      clinically significant upper eyelid retraction secondary to Graves' orbitopathy
      (GO). DESIGN: Prospective, single-blinded, comparative experimental study at a
      single institution. PARTICIPANTS: Patients from a single San Francisco Bay Area
      practice (RZS). METHODS: Consecutive patients with upper eyelid retraction
      secondary to GO who underwent surgical correction by transcutaneous mullerectomy
      were recruited between January and December 2011. An equal number of control MM
      specimens were gathered in consecutive patients undergoing conjunctivo-MM
      resection for ptosis correction. A total of 10 specimens in each group was
      available for analysis. The proportion of fat and fibrosis, as well as
      inflammatory markers, was studied and graded in both the study and the control
      group by a masked pathologist. These data were compared between groups using the
      Student t-test. RESULTS: No significant difference between the 2 groups of MM
      specimens was detected. CONCLUSIONS: Patients with quiescent GO with clinically
      significant eyelid retraction exhibit normal MM histology.

PMID- 24314406
TI  - Relationship between cataract severity and socioeconomic status.
AB  - OBJECTIVE: To determine the relationship between cataract severity and
      socioeconomic status (SES). DESIGN: Retrospective, observational case series. A
      total of 1350 eyes underwent phacoemulsification cataract extraction by a single
      surgeon using an Alcon Infiniti system. Cataract severity was measured using
      phaco time in seconds. SES was measured using area-level aggregate census data:
      median income, education, proportion of common-law couples, and employment rate.
      Preoperative best corrected visual acuity was obtained and converted to logarithm
      of the minimum angle of resolution values. For patients undergoing bilateral
      surgery, the generalized estimating equation was used to account for the
      correlation between eyes. Univariate analyses were performed using simple
      regression, and multivariate analyses were performed to account for variables
      with significant relationships (p < 0.05) on univariate testing. Sensitivity
      analyses were performed to assess the effect of including patient age in the
      controlled analyses. RESULTS: Multivariate analyses demonstrated that cataracts
      were more severe when the median income was lower (p = 0.001) and the proportion
      of common-law couples living in a patient's community (p = 0.012) and the
      unemployment rate (p = 0.002) were higher. These associations persisted even when
      controlling for patient age. CONCLUSION: Patients of lower SES have more severe
      cataracts.

PMID- 24314407
TI  - Haptic-induced postoperative complications. Evaluation using ultrasound
      biomicroscopy.
AB  - OBJECTIVE: Evaluation of haptic-induced postoperative complications with single
      piece intraocular lenses (IOLs) using ultrasound biomicroscopy (UBM). DESIGN: A
      retrospective case series. PARTICIPANTS: We looked at 5 pseudophakic eyes with
      noninfectious postoperative complications, after undergoing phacoemulsification
      with posterior chamber intracapsular IOL placement. METHODS: A review of clinical
      findings as well as UBM measurements looking at the distance of the IOL from the
      posterior surface of the pupil on each side of the lens. RESULTS: In all cases,
      UBM revealed malposition of the IOL, confirming IOL tilting and haptic
      displacement outside of the capsular bag. CONCLUSIONS: UBM is a useful tool for
      early diagnosis of uveitis-glaucoma-hyphema syndrome because it enables
      visualization of the exact position of the IOL in vivo. In such cases,
      localization of the lens and haptics are essential in devising treatment
      strategies, such as repositioning of the haptics, haptic amputation, or removal
      of the IOL.

PMID- 24314408
TI  - Immediately sequential bilateral cataract surgery: a cost-effective procedure.
AB  - OBJECTIVE: The objective of this project was to perform a cost-effectiveness
      analysis (CEA) of immediately sequential bilateral cataract surgery (ISBCS)
      versus delayed sequential bilateral cataract surgery (DSBCS) to determine whether
      ISBCS represents an appropriate, cost-effective way to rapidly rehabilitate a
      patient's visual impairment. DESIGN: A systematic review followed by a primary
      economic analysis with computer-based econometric modeling. PARTICIPANTS: Not
      applicable. METHODS: We constructed a decision analytic model from the
      perspective of the public third-party payer (i.e., the Ministry of Health) to
      conduct a CEA of both surgeries, ISBCS and DSBCS. Cost data consisted of the
      costs of the surgery, intravitreal injections, medications, and drops, all of
      which were obtained from a comprehensive literature search and from records at
      St. Joseph's Hospital, London, Ont. The effectiveness was measured by the utility
      values associated with visual acuity in the better seeing eye. RESULTS: ISBCS
      resulted in an incremental effectiveness of 0.08 utility at an incremental cost
      of $1607. Discounting the quality-adjusted life-years (QALYs) gained by an annual
      interest rate of 3% resulted in 0.932 QALYs gained. The cost-effectiveness of
      ISBCS was calculated to be $1431 per QALY gained. A 1-way sensitivity analysis
      was performed by varying costs, utility values, probabilities, and discounting
      rates. This analysis varied the incremental cost-effectiveness ratio but did not
      change the conclusion. CONCLUSIONS: Health economics assessment showed that,
      compared with DSBCS, ISBCS is a cost-effective procedure. This finding will be
      highly useful to policy-makers, decision-makers, clinicians, hospital
      administrators, and payers in making cost-efficient decisions.

PMID- 24314409
TI  - Role of ultra-widefield fluorescein angiography in the management of uveitis.
AB  - OBJECTIVE: To discuss and illustrate the role of ultra-widefield fluorescein
      angiography (UWFFA) in the diagnosis and management of peripheral retinal
      vasculitis. DESIGN: Retrospective case series. PARTICIPANTS: Four consecutive
      patients in whom UWFFA showed far peripheral vasculitis were included. All
      patients were seen between May 2011 and May 2012 at the Doheny Eye Institute.
      METHODS: Conventional fluorescein angiogram (FA) images or areas determined by
      the Early Treatment of Diabetic Retinopathy Study Group protocol for imaging the
      posterior pole and peripheral retina were superimposed on the UWFFA images. The
      ability to detect the extent and severity of vasculitis and vascular occlusion
      using both conventional FA and UWFFA was compared by 2 investigators, and any
      discrepancies were adjudicated by a third investigator. RESULTS: In none of the
      cases was the full extent of vasculitis and capillary occlusion visible in the
      fields normally portrayed by conventional FA. In contrast, capillary nonperfusion
      and peripheral vasculitis were detectable by UWFFA in all cases. In 2 cases, the
      posterior extent of vasculitis could have been detected by conventional FA.
      CONCLUSIONS: Detection and depiction of the extent and severity of peripheral
      vascular changes are enhanced with UWFFA, aiding in the management of vasculitis
      in the retinal periphery.

PMID- 24314410
TI  - Retinal NFL thinning on OCT correlates with visual field loss in pediatric
      craniopharyngioma.
AB  - OBJECTIVE: To investigate the use of peripapillary optical coherence tomography
      for monitoring optic neuropathy in pediatric craniopharyngioma. DESIGN:
      Retrospective, consecutive-cohort, single-centre chart analysis. PARTICIPANTS:
      Twenty children with craniopharyngioma treated at a pediatric medical centre from
      1999 to 2011. METHODS: The medical files were reviewed for demographics and optic
      nerve function. Findings for visual acuity and visual fields were analyzed
      against repeated optical coherence tomography (OCT) measurements of peripapillary
      nerve fibre layer thickness (using either time-domain Stratus OCT or spectral
      domain Cirrus OCT). RESULTS: Average age at diagnosis was 6.5 +/- 3.88 years. The
      most common presenting symptom was headache; only 1 child complained of visual
      loss. Mean best corrected visual acuity (logMAR) was 0.036 +/- 0.06 in the 17
      healthy eyes and 1.05 +/- 1.45 in the 23 eyes with optic neuropathy. Positive
      signs included relative afferent pupillary defect (8/20), visual acuity loss
      (7/20), temporal visual field loss (bilateral 4/15, unilateral 4/15), papilledema
      (3/20), and unilateral/bilateral optic disc pallor (14/20). RNFL thickness was
      significantly lower in eyes with optic neuropathy than in healthy eyes (65 +/- 22
      um vs 86.2 +/- 29 um; p = 0.000) and correlated with visual acuity (r = -0.43 to 
      0.17, p = 0.0001) and presence or absence of a visual field defect (mean
      difference, 26.1 +/- 5.8 um, p = 0.003). Ten children showed no change in RNFL
      thickness over time (mean 18 +/- 14.2 months). CONCLUSIONS: A thinner RNFL on
      ocular coherence tomography is correlated with poorer visual acuity and visual
      field loss. Ocular coherence tomography may serve as an objective method to
      quantify axonal loss caused by craniopharyngioma. Further investigation is needed
      to determine its use for evaluating progressive axonal loss over time.

PMID- 24314411
TI  - Lateral rectus recession with/without transposition in V-pattern exotropia
      without inferior oblique overaction.
AB  - OBJECTIVE: To compare bilateral lateral rectus (BLR) recession with BLR recession
      combined with half-tendon upward transposition in the management of patients with
      V-pattern exotropia (XT; 15-20 prism diopters [PD] greater XT in upgaze than
      downgaze) with no or minimal inferior oblique overaction. DESIGN: Retrospective,
      observational, cohort study. PARTICIPANTS: Twenty-nine patients had BLR recession
      (Group A). Twenty-one patients had BLR recession combined with half-tendon upward
      transposition (Group B). METHODS: A retrospective study was performed on patients
      with V-pattern XT with no or minimal inferior oblique overaction. Ductions,
      versions, pattern strabismus, stereoacuity, and degree of fundus torsion were
      analyzed in all patients before and after surgery. Patients were included in the
      study only if they achieved a minimum follow-up of 6 months. RESULTS:
      Normalization of V pattern (<5Delta) was achieved in 14% in Group A and 64% in
      Group B (p < 0.001). Mean reduction in V pattern after surgery was 7Delta +/-
      6Delta in Group A and 13Delta +/- 4Delta in Group B (p < 0.001). No change in
      fundus intorsion occurred in Group A, whereas fundus extorsion occurred in 8
      patients (44%) in Group B. Orthophoria within 8Delta in the primary position was
      achieved in 79% in Group A and 82% in Group B (p = 1.00). There was no
      statistically significant difference in the postoperative stereoacuity in both
      groups (p = 0.67). CONCLUSIONS: BLR with half-tendon upward transposition is much
      more effective than BLR recession alone in correcting V pattern.

PMID- 24314412
TI  - The precision of ophthalmic biometry using calipers.
AB  - OBJECTIVE: The purpose of the study is to determine the precision of whole globe
      and cornea measurements acquired using calipers, and to quantify the
      intraoperator and interoperator variance. DESIGN: Experimental study.
      PARTICIPANTS: Ten human donor eyes. METHODS: Ten human eyes (donor age, 16-54
      years) were obtained between 18.5 and 66.5 hours postmortem. The horizontal and
      vertical diameters and the anteroposterior length of the globe were measured
      using a digital Vernier caliper. The horizontal and vertical diameters of the
      cornea were measured using both a digital Vernier caliper and a Castroviejo
      caliper. The measurements were performed by 3 operators with 5 repeat
      measurements for each dimension. RESULTS: No significant differences were
      observed between measurements of globe anteroposterior length, horizontal
      diameter, and vertical diameter. Horizontal corneal diameter was greater than
      vertical diameter with all instruments and all operators. Variability of either
      instrument did not change with measurement object scale, and was similar across
      all operators. No significant differences were observed between the variabilities
      of the 2 devices. The mean intraoperator SD was 0.127 +/- 0.023 mm with the
      digital caliper and 0.094 +/- 0.056 mm with the Castroviejo caliper. CONCLUSIONS:
      The precision of commercially available calipers in ophthalmic biometry
      measurements is limited to approximately 0.1 mm.

PMID- 24314414
TI  - Sandwich fibrin glue technique for attachment of conjunctival autograft during
      pterygium surgery.
AB  - OBJECTIVE: To report the results of a sandwich application of fibrin glue
      compared with the standard method of using fibrin glue for the attachment of the
      conjunctival autograft in pterygium surgery. PARTICIPANTS: The study group
      consisted of 56 consecutive eyes with primary pterygium. METHODS: We performed a
      retrospective analysis comparing the standard method of using fibrin glue for the
      attachment of the conjunctival autograft during pterygium excision surgery versus
      the "sandwich technique." In the "sandwich technique," the thrombin component of
      the fibrin glue was applied after the graft was secured in position over a bed of
      fibrinogen. RESULTS: Graft dehiscence occurred in 3 eyes in the conventional
      group only. Recurrence occurred in 2 eyes in the conventional group and 1 eye in
      the sandwich group. None of the values reached statistical significance.
      CONCLUSIONS: The sandwich technique simplifies conjunctival graft fixation during
      pterygium surgery with conjunctival autograft by allowing more time to properly
      position the autograft before fibrin clot formation.

PMID- 24314415
TI  - Sequential pterygium excision with conjunctival autograft in the management of
      primary double-headed pterygia.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of sequential
      pterygium excision with conjunctival autograft (PECA) in the management of double
      headed pterygia. METHODS: All patients who underwent a sequential PECA procedure
      for double-headed pterygia from 2004 to 2009 were included in this retrospective,
      noncomparative, interventional case series. The recurrence rate and visual
      outcomes after this procedure were determined. RESULTS: Nine eyes of 8 patients
      with doubled-headed pterygia undergoing sequential PECA were identified. Of 18
      PECA procedures, 1 recurrence (5.56%) was found. The single recurrence was
      observed nasally in the right eye (first site operated) of a female patient 55
      months after the second PECA procedure. None of the operated eyes lost any lines
      of corrected distance visual acuity, and 22% gained at least 1 line of corrected
      distance visual acuity. CONCLUSIONS: In this series, harvesting the conjunctival
      autograft from the same site several months later does not appear to increase the
      rate of recurrence. Sequential PECA is a safe and effective method of addressing
      double-headed pterygia.

PMID- 24314413
TI  - The Ultrachopper tip: a wound temperature study.
AB  - PURPOSE: To determine the thermal characteristics of the Ultrachopper and its
      thermal properties in varied viscosurgical substances. DESIGN: Experimental
      study. PARTICIPANTS: Not applicable. METHODS: The Ultrachopper (Alcon, Inc) tip
      with the Infiniti (Alcon, Inc) handpiece was attached to a thermistor and placed
      in a test chamber filled with either an ophthalmic viscosurgical device (OVD) or
      balanced salt solution (BSS). The thermistor allowed for continuous monitoring of
      temperature from baseline and the change that occurred over 60 seconds of
      continuous run time. RESULTS: Mean maximum temperature in each OVD exceeded 50
      degrees C over the first 25 seconds of continuous run time. The mean maximum
      temperature was statistically significantly higher with all OVDs (p < 0.0001)
      when compared with BSS. A small but statistically significant difference in mean
      maximum temperature was shown between Healon 5 (AMO, Inc) and Viscoat (Alcon,
      Inc) (p < 0.05). The linear increase in temperature was statistically
      significantly different with all OVDs compared with BSS (p < 0.0001).
      CONCLUSIONS: The thermal properties of the Ultrachopper tip demonstrate a heat
      generating capacity that achieves published thresholds for risk for wound burn.

PMID- 24314416
TI  - No ocular motility complications after subtenon topotecan with fibrin sealant for
      retinoblastoma.
AB  - OBJECTIVE: To report our long-term experience with the local toxicity profile and
      ocular motility changes after treatment of intraocular retinoblastoma with
      subtenon topotecan chemotherapy. DESIGN: Cross-sectional study. PARTICIPANTS: Ten
      eyes in 8 patients with retinoblastoma treated with subtenon topotecan. METHODS:
      We assessed potential complications in ocular motility in eyes with
      retinoblastoma treated with subtenon topotecan using forced duction testing under
      general anaesthesia. Eyes subsequently enucleated because of treatment failure
      were examined histologically. RESULTS: Ten eyes in 8 patients with retinoblastoma
      treated with 1 to 4 injections of subtenon topotecan were examined repeatedly,
      with a mean follow-up period of 37 months. Ocular motility remained normal in all
      eyes by forced duction, with no observed persistent conjunctival congestion,
      abnormal ocular motility, or enophthalmos in retained eyes 3 years after last
      injection. Histopathologic examination of the 2 enucleated eyes did not reveal
      signs of orbital tissue necrosis or fibrosis. CONCLUSIONS: Unlike subtenon
      carboplatin, subtenon topotecan therapy is not associated with long-term toxicity
      affecting ocular muscles or orbital soft tissue. No effect on ocular motility was
      observed.

PMID- 24314417
TI  - Minimal trephination penetrating keratoplasty for severe fungal keratitis
      complicated with hypopyon.
AB  - OBJECTIVE: To report outcomes after minimal trephination penetrating keratoplasty
      (PKP) in the treatment of severe fungal keratitis complicated with hypopyon.
      DESIGN: Retrospective case series. PARTICIPANTS: Series of 19 eyes in 19 patients
      with severe fungal keratitis complicated with hypopyon that received minimal
      trephination PKP. METHODS: The host trephination was made equal to or smaller
      than the margin of the corneal lesion. Fluconazole (0.2%) was used to irrigate
      the trephined edge and anterior chamber during surgery, followed by irrigation of
      the anterior chamber with a 0.02% fluconazole solution after graft
      transplantation. Postoperative complications, graft rejection, transparency rate,
      and visual acuity were recorded. RESULTS: Patients were followed postoperatively
      for 18 to 34 months (mean 28.6 months). At 18 months after PKP, 18 grafts (94.7%)
      remained clear and 14 eyes (73.7%) had improved visual acuity. Three eyes (15.8%)
      with secondary glaucoma complications after PKP were treated with subsequent
      trabeculectomy. Recurrent infection was found in only 1 eye (5.26%) after
      transplantation and was successfully managed. Immune graft rejections were not
      observed in any patient during the follow-up period. CONCLUSIONS: The minimal
      trephination technique in combination with antifungal therapy was effective in
      the treatment of severe fungal keratitis with large corneal lesions and hypopyon.

PMID- 24314418
TI  - Analysis of choroidal thickness in eyes treated with focal laser photocoagulation
      using SD-OCT.
AB  - OBJECTIVE: To analyze the effect of focal laser photocoagulation on choroidal
      thickness in patients with diabetic macular edema (DME), using spectral-domain
      optical coherence tomography (SD-OCT). DESIGN: Retrospective review.
      PARTICIPANTS: Twenty-two eyes of 22 patients diagnosed with DME and treated with
      focal laser photocoagulation (treatment group) and 19 fellow treatment-naive eyes
      (control group) who underwent high-definition 1-line raster scanning using the
      Cirrus SD-OCT at the New England Eye Center, Tufts Medical Center (Boston, Mass.)
      between November 2009 and April 2012. METHODS: The SD-OCT images were analyzed
      for the measurement of choroidal thickness by 2 independent observers experienced
      in analyzing OCT images, before treatment and at 3 months after focal laser
      photocoagulation in the treatment group, and at baseline (when the fellow eye in
      the treatment group was treated) and at 3-month follow-up in the control group.
      RESULTS: There was no significant difference in the mean choroidal thickness in
      the treatment and control groups (n = 22, p = 0.93 and n = 19, p = 0.1,
      respectively) at 3-month follow-up. There was no significant association of the
      number of focal laser treatments with the mean choroidal thickness (n = 41, r = 
      0.31, p = 0.68). CONCLUSIONS: Focal laser photocoagulation does not appear to
      alter choroidal thickness in eyes with DME in the short term, as assessed using
      SD-OCT. Long-term follow-up of eyes with DME and other retinal diseases treated
      with laser photocoagulation may provide further insight into the effects of this
      treatment modality on the choroid.

PMID- 24314419
TI  - Grading of posterior staphyloma with spectral-domain optical coherence tomography
      and correlation with macular disease.
AB  - OBJECTIVE: To develop a novel grading system for posterior staphyloma imaged by
      spectral-domain optical coherence tomography (SD-OCT) and to correlate the
      incidence of macular disease (vitreomacular traction, epiretinal membrane,
      macular schisis, lamellar macular hole, and full-thickness macular hole) with
      each grade. DESIGN: Retrospective chart review. PARTICIPANTS: A total of 150 eyes
      from 89 patients with posterior staphylomas were examined at Jules Stein Eye
      Institute, University of California Los Angeles. METHODS: Retrospective analysis
      of the Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, Calif.) database at a large
      institution (Jules Stein Eye Institute) was performed and eyes with a posterior
      staphyloma involving the macula were evaluated for the presence of macular
      pathology. The radius of each circle was measured and graded, and the incidence
      of macular pathology was correlated with each staphyloma grade. Statistical
      analysis was done using Fisher exact and Kruskal-Wallis tests. RESULTS: The
      overall incidence rate of macular disease was 50.6% (76/150 eyes). The incidence
      rate of macular schisis was 17.3% (26/150) and was significantly greater with
      steeper (grade 3 [25.0%] and grade 4 [30.3%] staphyloma) versus shallower grade
      (grade 1 [5.6%]) staphyloma (p = 0.016). CONCLUSIONS: Imaging of staphyloma via
      SD-OCT is a valuable tool for determining the severity of posterior staphyloma
      and for determining risk stratification for various macular diseases.

PMID- 24314420
TI  - Risk stratifying retinal breaks.
AB  - OBJECTIVE: Argon laser retinopexy has been the primary treatment for retinal
      breaks for many decades. Prevention of progression to retinal detachment (RD) is
      the main objective. The benefit of laser retinopexy is well documented, although
      little has been reported on the risk factors for progression to RD. By addressing
      this issue, patients at high risk can be identified, and more timely specialist
      retinal input can be sought. METHODS: Data over a 6-month period from 45
      consecutive patients undergoing laser retinopexy were reviewed. Patients were
      categorized into complete success (no more than 1 laser treatment), qualified
      success (no more than 3 laser or cryotherapy treatments), and treatment failure
      (more than 3 laser or cryotherapy treatments or progression to RD). RESULTS:
      Complete success was observed in 53.5% of patients, a further 34.9% of patients
      achieved a qualified success, and the remainder of the patients (11.6%) fell into
      the treatment failure category. About 9.3% of patients required cryotherapy, and
      7.0% of patients underwent RD surgery. Patients with a bridging blood vessel and
      vitreous hemorrhage were significantly more likely to be in the treatment failure
      category than those without. RD was significantly associated with the presence of
      vitreous hemorrhage. CONCLUSIONS: Patients with retinal breaks associated with
      bridging blood vessels and vitreous hemorrhage are at greater risk for poorer
      outcome. The area of subretinal fluid was not linked to failure. If complete
      laser of a tear is not possible or if concerns remain regarding treatment
      efficacy, prompt referral to a retina specialist for further management is
      recommended.

PMID- 24314421
TI  - Predictors of treatment failure for pneumatic retinopexy.
AB  - OBJECTIVE: The purpose of this study was to define the overall anatomic success
      rate in pneumatic retinopexy and to identify morphologic features that may be
      predictive of treatment failure in pneumatic retinopexy. DESIGN AND PARTICIPANTS:
      Prospective consecutive interventional case series of patients with new-onset
      primary rhegmatogenous retinal detachments treated with pneumatic retinopexy.
      METHODS: In this interventional case series, consecutive patients with new-onset
      primary rhegmatogenous retinal detachments were treated with pneumatic retinopexy
      and followed prospectively. Morphologic data were collected on 3-colour fundus
      drawings. The primary outcome measure was treatment failure, defined as
      requirement for scleral buckle or vitrectomy within the follow-up period. Rates
      of failure for each morphologic feature were compared and a logistic regression
      model was fit. RESULTS: A total of 113 eyes were included in the study. Anatomic
      success was achieved in 69.6% of patients. Morphologic criteria including the
      position and number of breaks, position and extent of lattice degeneration, size
      of the detached area, and macular status were all found not to be significantly
      related to failure. In multivariate analysis, only 3 predictors, pseudophakic
      status (p < 0.05, odds ratio [OR] 2.9, 95% CI, 1.06-7.88), presence of retinal
      break greater than 1 clock-hour (p < 0.05, OR 3.41, 1.06-11.02), and presence of
      grade C or D proliferative vitreoretinopathy (PVR) (p < 0.01, OR 31.83, 95% CI,
      3.59-282.24), gained statistical significance. CONCLUSIONS: Only pseudophakia, a
      large retinal break, and/or PVR was associated with an increased likelihood of
      failure.

PMID- 24314422
TI  - Effect of anterior chamber paracentesis on initial treatment of acute angle
      closure.
AB  - OBJECTIVE: To compare anterior chamber paracentesis (ACP) with standard medical
      management of acute primary angle closure (APAC). DESIGN: Prospective study.
      PARTICIPANTS: Patients with APAC and intraocular pressure (IOP) >= 50 mm Hg were
      enrolled. METHODS: Patients were randomized to receive ACP and medical treatment
      (group 1) or medical management alone (group 2). RESULTS: There were 26 patients
      (mean age 69.3 +/- 10.4 years, 31 eyes) in group 1 and 28 patients (mean age 67.0
      +/- 9.7 years, 30 eyes) in group 2. The IOP in group 1 was significantly lower at
      15 minutes, 30 minutes, and 1 hour after treatment (p < 0.05). At 1, 2, and 24
      hours after treatment, visual acuity was significantly better in group 1 than in
      group 2. At each time point after treatment, the grade of corneal edema was not
      different between the groups. Pain score at 1 and 2 hours after treatment was
      significantly lower in group 1 than in group 2; however, no difference was noted
      at 24 hours after treatment. The mean follow-up period in group 1 was 16.1 +/-
      1.3 months and in group 2 was 15.6 +/- 1.4 months (p = 0.803). At last follow-up,
      IOP, pupil size, number of eyes with nonreactive pupils, and centre endothelial
      cell counts were not different; however, visual acuity was significantly better
      in group 1 (0.43 +/- 0.06 logMAR vs 0.74 +/- 0.10 logMAR, p = 0.007).
      CONCLUSIONS: Immediate ACP is a safe and effective for rapidly lowering IOP, and
      is associated with better visual acuity than medical treatment alone.

PMID- 24314423
TI  - The great masquerade: delayed diagnosis of mucopolysaccharidosis in adulthood.

PMID- 24314424
TI  - Temporal pellucid marginal degeneration displaying high "with-the-rule"
      astigmatism.

PMID- 24314425
TI  - A novel TGM1 splicing mutation in a collodion baby with cicatricial ectropion.

PMID- 24314426
TI  - Valsalva hemorrhagic retinopathy during labour: a case report and literature
      review.

PMID- 24314427
TI  - Macular hole following Rickettsia conorii infection.

PMID- 24314428
TI  - Case of acquired night blindness in a hemodialysis patient.

PMID- 24314429
TI  - Clinicopathologic case reports of Alternaria and Fusarium keratitis in Canada.

PMID- 24314430
TI  - Pigmented conjunctival growing lesion in a teenager: nevus or melanoma?

PMID- 24314431
TI  - Orbital signet-ring cell lymphoma of diffuse, large, B-cell type.

PMID- 24314432
TI  - Invasive conjunctival squamous cell carcinoma presenting with serous retinal
      detachment.

PMID- 24314433
TI  - Tonic pupil, anterior ischemic optic neuropathy in a teenager with Takayasu
      arteritis.

PMID- 24314434
TI  - Severe eyelid injury resulting from necrotic arachnidism in a child with
      leukemia.

PMID- 24314435
TI  - Periorbital lipogranuloma after cryopreserved autologous fat injection at
      forehead: unexpected complication of a popular cosmetic procedure.

PMID- 24314436
TI  - Monoclonal gammopathy of undetermined significance maculopathy.

PMID- 24314437
TI  - Herpetic acute anterior uveitis complicated by retinal vasculitis in an
      immunocompetent child.

PMID- 24314438
TI  - Intraventricular hemorrhage and oral ibuprofen in very low birth weight preterm
      infants.

PMID- 24314439
TI  - Corneal arcus as first sign of familial hypercholesterolemia.

PMID- 24314440
TI  - Blunt abdominal trauma to a pregnant woman resulting in a child with hemiplegic
      spastic cerebral palsy and permanent eye damage.
AB  - BACKGROUND: In today's life trauma is a common and important complication of
      pregnancy and remains one of the major contributors to maternal and fetal
      morbidity and mortality. CASE PRESENTATION: The authors reported a case of 4
      years old child with hemiplegic spastic cerebral palsy and permanent left eye
      damage due to antenatal trauma. He was an off spring to a 33 years old woman
      gravida 6 para 5 from western Sudan, who sustained a domestic blunt abdominal
      trauma during her routine daily activities. The abdominal trauma occurred during
      the third trimester at 36th week gestation of the pregnancy when the mother hit
      herself by the woody part of an axe non intentionally. CONCLUSIONS: The findings
      from this case conclude that relatively minor trauma can have significant adverse
      effects on the fetus and can be devastating.

PMID- 24314494
TI  - Review of population based coroners autopsy findings in Rivers state of Nigeria.
AB  - BACKGROUND: Sudden deaths are common findings in Rivers state of Nigeria. The
      victims of such deaths are subjects, of coroners' autopsies, and the records
      there from constitute important sources of epidemiological data. AIMS: To
      determine the pattern, causes and demographic features of all deaths reported to
      the coroner for medico legal autopsies in Rivers state of Nigeria. MATERIALS AND
      METHODS: Retrospective descriptive study on reports of coroner autopsies carried
      out between January 2000 and December 2010 in different mortuaries located across
      Rivers state was undertaken. The autopsies were unlimited and standardized.
      Information analyzed were: gender, age, circumstances of death and, autopsy
      defined cause of death. RESULTS: Of the 1987 cases reviewed, 83.4% were males.
      The age range was 2 weeks to 98 years with a mean of, 31.7 years. The peak age
      range was 21-30 years with 46.5%. The manners of deaths in descending order
      include: homicides with 50.5%, accidents with 32%, sudden natural deaths with
      14.1%, maternal deaths with 2.6% and suicides with 0.8%. Males were most affected
      in homicidal death with average male:female ratio of 12.4:1. Gunshots constituted
      the commonest means of homicidal deaths, with 67.9% while decapitation was the
      least with 0.1%. The commonest cause of accidental death was, road traffic
      accident with 63.6%. Cardiovascular system pathologies were the commonest causes
      of natural deaths with 46.1%. Illegal abortions with 41.1% were the commonest
      causes of maternal, deaths and all suicidal cases were committed by hanging.
      CONCLUSIONS: Homicides were by far the commonest findings of medico legal
      autopsies, followed by accidental and natural deaths respectively while suicides
      were the least in Rivers state of Nigeria. Firearms were the, most frequently
      used weapons for homicides and road traffic accidents remain the major causes of
      accidental deaths while cardiovascular system pathologies account for the highest
      proportion of sudden natural deaths and suicides are committed by hanging. Males
      within the productive age, brackets of 20-49 years are more affected by sudden
      deaths of all manners.

PMID- 24314495
TI  - A combined experimental and numerical study of stab-penetration forces.
AB  - The magnitude of force used in a stabbing incident can be difficult to quantify,
      although the estimate given by forensic pathologists is often seen as 'critical'
      evidence in medico-legal situations. The main objective of this study is to
      develop a quantitative measure of the force associated with a knife stabbing
      biological tissue, using a combined experimental and numerical technique. A
      series of stab-penetration tests were performed to quantify the force required
      for a blade to penetrate skin at various speeds and using different 'sharp'
      instruments. A computational model of blade penetration was developed using
      ABAQUS/EXPLICIT, a non-linear finite element analysis (FEA) commercial package.
      This model, which incorporated element deletion along with a suitable failure
      criterion, is capable of systematically quantifying the effect of the many
      variables affecting a stab event. This quantitative data could, in time, lead to
      the development of a predictive model that could help indicate the level of force
      used in a particular stabbing incident. 

PMID- 24314496
TI  - Post mortem sampling of the bladder for the identification of victims of fire
      related deaths.
AB  - In a coronial setting a deceased person must be formally identified. It is
      difficult to identify a deceased person when their physical features are
      disrupted and identification by visual means cannot occur. In the absence of
      visual identification, the confirmation of identity of a deceased person relies
      on the scientific comparison of information obtained post mortem with ante mortem
      information. The ante mortem information may include dental and medical records,
      fingerprints, and DNA profiling. For cases involving incinerated remains, this
      traditionally requires the collection of blood, muscle or bone samples from the
      deceased (depending on the severity of the burns) for DNA analysis and subsequent
      comparison to a reference sample for kinship determination. Following on from
      work conducted during the DVI response to a plane crash in Papua New Guinea in
      2011, a study has been performed examining the viability of utilising material
      obtained from bladder swabs in deaths associated with fires. Twenty-eight cases
      were analysed during 2012 with deaths occurring in motor vehicle and aviation
      accidents, as well as house fires, homicides and from self-immolation. Bladder
      and conventional (blood, muscle or bone) samples were subjected to DNA analysis
      and compared. Our findings demonstrate that the bladder samples all gave DNA of
      sufficient quality for DNA profiling. This easily obtained sample (when
      available) can be now recommended in the scientific identification process of
      fire affected deceased persons. 

PMID- 24314497
TI  - Silver nanoparticles doped agarose disk: highly sensitive surface-enhanced Raman
      scattering substrate for in situ analysis of ink dyes.
AB  - Raman spectroscopy is a preferred analytical tool for forensic trace analysis due
      to its non-invasive nature. This technique has been utilized in examination of
      organic colorants present in fibers and ink, but high fluorescent nature of these
      compounds is a problem. In the present study, silver-doped agarose gel disk,
      having property of quenching fluorescence and enhancing Raman signals, is found
      to be effective as surface-enhanced Raman scattering (SERS) substrates for
      analysis of rhodamine 6G (Rh 6G) and crystal violet (CV) dyes. As-prepared and
      well characterized by UV, TEM-EDAX and XRD techniques, the investigated silver
      doped agarose gel disk proves to have minimal invasive as confirmed by the ATR
      FTIR method and effective for in situ SERS analysis of blue and red ballpoint
      ink. The disk is stable upon storage and hence can be re-used and re-examined.
      The present method offers new possibilities in trace forensic analysis with
      minimal destruction. 

PMID- 24314498
TI  - Homicide-suicides compared to homicides and suicides: systematic review and meta
      analysis.
AB  - Homicide-suicides, the murder of one or several individuals followed by the
      suicide of the perpetrator, are rare but have devastating effects on families and
      communities. We did a systematic review and meta-analysis of studies comparing
      perpetrators of homicide-suicides with perpetrators of simple homicides and
      suicides and examined the proportion of firearm use and its correlation with
      firearm availability. We searched Medline and Embase from inception to July 2012
      and identified 27 eligible studies. Perpetrators of homicide-suicides were older
      and more likely to be male and married to or separated from their victims than
      perpetrator of simple homicides or suicides. Influence of alcohol and a history
      of domestic violence or unemployment were less prevalent in homicide-suicides
      than in homicides. The proportion of firearm use in homicide-suicides varied
      across countries and was highest in the USA, Switzerland and South Africa,
      followed by Australia, Canada, The Netherlands and England and Wales, with a
      strong correlation between the use of firearms and the level of civilian gun
      ownership in the country. Our results indicate that homicide-suicides represent a
      distinct entity, with characteristics distinguishing them both from homicides and
      suicides. 

PMID- 24314499
TI  - Elemental fingerprinting of soils using ICP-MS and multivariate statistics: a
      study for and by forensic chemistry majors.
AB  - Students in an instrumental analysis course with a forensic emphasis were
      presented with a mock scenario in which soil was collected from a murder
      suspect's car mat, from the crime scene, from adjacent areas, and from more
      distant locations. Students were then asked to conduct a comparative analysis
      using the soil's elemental distribution fingerprints. The soil was collected from
      Lafayette County, Mississippi, USA and categorized as sandy loam. Eight student
      groups determined twenty-two elements (Li, Be, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co,
      Ni, Cu, Zn, As, Se, Rb, Sr, Cs, Ba, Pb, U) in seven samples of soil and one
      sample of sediment by microwave-assisted acid digestion and inductively coupled
      plasma-mass spectrometry (ICP-MS). Data were combined and evaluated using
      multivariate statistical analyses. All eight student groups correctly classified
      their unknown among the different locations. Students learn, however, that
      whereas their results suggest that the elemental fingerprinting approach can be
      used to distinguish soils from different land-use areas and geographic locations,
      applying the methodology in forensic investigations is more complicated and has
      potential pitfalls. Overall, the inquiry-based pedagogy enthused the students and
      provided learning opportunities in analytical chemistry, including sample
      preparation, ICP-MS, figures-of-merit, and multivariate statistics. 

PMID- 24314501
TI  - Escalation of methamphetamine-related crime and fatalities in the Dresden region,
      Germany, between 2005 and 2011.
AB  - Methamphetamine (MA), a central nervous system stimulating recreational drug, is
      a worldwide problem related to crime as well as forensic and health aspects. The
      data, exemplarily presented in this study for the Dresden region, Saxony,
      Germany, demonstrate the escalation of MA-related crime and fatalities between
      2005 and 2011. Easy availability and an attractive price of MA in the Czech
      Republic are responsible for both the increase of the occurrence of MA in
      relation to the entire drug crime as well as the increase of the occurrence of MA
      positive cases of driving under influence (DUI). Higher percentage of very pure
      MA on the Saxon drug market since 2010 seems to be the reason for the fatalities
      directly caused by MA in 2010 and 2011. 

PMID- 24314500
TI  - Postmortem 3-D reconstruction of skull gunshot injuries.
AB  - BACKGROUND: In cases of severe decomposition or skeletonization of a corpse after
      cerebral gun shot injury it is difficult to exactly reconstruct the bullet path
      in the brain. However, in case of murder or homicide this might become necessary
      to answer forensic questions such as the ability to move or other actions of the
      victim. MATERIALS AND METHODS: Therefore a method in terms of three dimensional
      reconstruction technique was developed by fusing computed tomography scans (CT)
      of the original skull and magnetic resonance images (MRI) of a normal brain of
      adequate size. Hereby five cases were investigated. RESULTS: In three cases an
      excellent concordance between the reconstructed bullet trajectory and the autopsy
      reports was achieved. In one case the original brain was not available for CT
      scanning due to previous autopsy. However, the findings were in line with the
      pathology report. In one case there was a difference of about 1-2 cm between the
      original autopsy description and the reconstructed bullet path. This was due to
      only a part of the skull being available for image reconstruction. CONCLUSION:
      The findings suggest that this method can successfully be applied to adequately
      reconstruct bullet paths in cases of completely skeletonized skulls, but should
      carefully be used in cases of incomplete skulls.

PMID- 24314502
TI  - Residues from low-order energetic materials: the comparative performance of a
      range of sampling approaches prior to analysis by ion chromatography.
AB  - A quantitative study of common forensic evidence collection devices for the
      recovery of low-explosive residues from non-porous glass and plastic is presented
      herein. Swabbing materials including cotton, rayon, Nomex((r))
      (poly(isophthaloylchloride/m-phenylenediamine)), Teflon/Teflon-coated fibreglass
      (polytetrafluoroethylene) and adhesive-coated tapes were used to collect known
      quantities of up to 14 forensically relevant inorganic and organic anion and
      cation species from both surfaces. Analysis was performed using two validated ion
      chromatography methods. This study revealed that all swabs and surfaces
      contributed highly variable levels of interfering ionic species and that swabbing
      materials showed variance in the quantities and total number of analytes
      recovered from both surfaces. Teflon and Nomex((r)) materials demonstrated the
      most promise due to their ability to collect and release analytes into simple
      extraction solvents as well as displaying relatively low endogenous interference.
      In parallel, the ability to extract residue directly from both surfaces via the
      addition of a suitable extraction solvent was investigated instead of swabbing.
      This work highlights that direct solvent extraction from a surface should be
      considered as an alternative approach, especially for small areas or objects. To
      the best of our knowledge, this work represents the most comprehensive study of
      the efficiencies of sample collection technologies for low-explosive residues
      prior to analysis by ion chromatography. 

PMID- 24314503
TI  - A fast liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF
      MS) method for the identification of organic explosives and propellants.
AB  - A fast, highly specific and sensitive method for the detection of an extensive
      list of organic explosives and propellants using an optimised Liquid
      Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS) procedure
      has been developed. Analyte specific information including retention time, adduct
      accurate mass and fragmentation data was firstly collected using both positive
      and negative ion Atmospheric Pressure Chemical Ionisation (APCI) and entered into
      a Personal Compound Database/Library (PCDL). The custom PCDL can then be used to
      screen any sample for the presence of organic explosives and propellants,
      generating a match score for any identified compounds. To date over 50 organic
      explosives and propellants have been characterised and entered into the database
      representing those likely to be encountered in forensic and environmental samples
      and also a range of specialist explosives. 

PMID- 24314504
TI  - Identification using face regions: application and assessment in forensic
      scenarios.
AB  - This paper reports an exhaustive analysis of the discriminative power of the
      different regions of the human face on various forensic scenarios. In practice,
      when forensic examiners compare two face images, they focus their attention not
      only on the overall similarity of the two faces. They carry out an exhaustive
      morphological comparison region by region (e.g., nose, mouth, eyebrows, etc.). In
      this scenario it is very important to know based on scientific methods to what
      extent each facial region can help in identifying a person. This knowledge
      obtained using quantitative and statical methods on given populations can then be
      used by the examiner to support or tune his observations. In order to generate
      such scientific knowledge useful for the expert, several methodologies are
      compared, such as manual and automatic facial landmarks extraction, different
      facial regions extractors, and various distances between the subject and the
      acquisition camera. Also, three scenarios of interest for forensics are
      considered comparing mugshot and Closed-Circuit TeleVision (CCTV) face images
      using MORPH and SCface databases. One of the findings is that depending of the
      acquisition distances, the discriminative power of the facial regions change,
      having in some cases better performance than the full face. 

PMID- 24314505
TI  - Markers of acidosis and stress in a sprint versus a conducted electrical weapon.
AB  - Both profound acidosis and catecholamine excess have been proposed as underlying
      physiologic derangements in subjects at high risk for arrest related death (ARD).
      In this study, the objective was to determine a level of physical exertion that
      is "equivalent" in terms of levels of acidosis and catecholamines to a "standard"
      TASER X26 exposure. Data were collected on subjects who underwent a 5-s TASER X26
      exposure or a sprint of variable distances during a law enforcement training
      exercise. Our results show that levels of acidosis and catecholamines are less
      among subjects exposed to the TASER X26 than among subjects who sprinted 20 yards
      or more. 

PMID- 24314506
TI  - Rib fractures at postmortem computed tomography (PMCT) validated against the
      autopsy.
AB  - To evaluate the sensitivity of postmortem computed tomography (PMCT) in rib
      fracture detection validated against autopsy. Fifty-one forensic cases underwent
      a postmortem CT prior to forensic autopsy. Two image readers (radiologist and
      forensic pathologist) assessed high resolution CT data sets for rib fractures.
      Correct recognition rates (CRR), sensitivity and specificity values were
      calculated over all observations as well as individually for every rib and
      region. Additionally, for partial rib fractures the sensitivity of autopsy was
      calculated vice versa. 3876 entries in each study protocol (autopsy, PMCT
      radiologist and PMCT forensic pathologist) were investigated. A total of 690
      fractures (autopsy), 491 (PMCT and radiologist) and 559 (PMCT and forensic
      pathologist) were detected. The CRR was 0.85. Sensitivity and specificity of PMCT
      for rib fracture detection were 0.63 (0.58 radiologist, 0.68 forensic
      pathologist) and 0.97 (both readers 0.97), respectively. Low CRR and sensitivity
      values were obtained for antero-lateral fractures. Partial rib fractures were
      better detected by PMCT. PMCT has a rather low sensitivity for rib fracture
      detection when validated against autopsy and indicates that clinical CT may also
      demonstrate a reasonable number of false negatives. Partial rib fractures often
      remain undetected at autopsy. 

PMID- 24314507
TI  - Survival time estimation using Injury Severity Score (ISS) in homicide cases.
AB  - The aim of our study was to assess the value of ISS to estimate survival time in
      a retrospective study of all homicidal deaths in the Western suburbs of Paris
      between 1994 and 2008. Stab wounds were the most common cause of death. Survival
      time between assault and death, determined in 107 cases out of 511 homicide
      cases, ranged from 0 min to 25 days (mean 39 h). There was an overall significant
      association between the survival time and the ISS score. ISS and survival time
      were strongly associated with male victims and a clear trend was seen with women.
      Regarding the type of wounds, a trend was seen with gunshot wounds and blunt
      injuries, but not with stab wounds. There was no influence of blood toxicological
      results and resuscitation attempts. Overall, ISS was a good predictor of a
      survival under 30 min.

PMID- 24314508
TI  - LumicyanoTM: a new fluorescent cyanoacrylate for a one-step luminescent latent
      fingermark development.
AB  - Latent fingermarks developed by cyanoacrylate fuming often lack contrast;
      therefore further enhancement is required, such as dye staining. This second step
      is part of the conventional detection sequences performed by forensics
      practitioners. Dye-staining or powder dusting aims at improving contrast and at
      increasing the legibility of details, yet their use may at times be limited.
      Indeed powder dusting may not be effective due to unexpected adherence to the
      background, and poor affinity to the cyanoacrylate. In the same way staining
      processes can dye a whole semi-porous surface or may wash the marks. To avoid
      that second step, a new luminescent cyanoacrylate (LumicyanoTM) which allows one
      step development without changing the fuming chamber settings (80% humidity rate,
      120 degrees C fuming temperature) was developed and assessed. This study aimed at
      comparing LumicyanoTM to a conventional two-step process. A detailed sensitivity
      study was conducted on glass slides, as well as the processing of various non
      porous and semi-porous substrates, usually considered as problematic for a dye
      staining step. The results indicate that LumicyanoTM detects fingermarks with
      equal or better sensitivity and ridge details than currently used cyanoacrylate.
      Secondly in luminescent mode, good ridges clarity and excellent contrast are
      observed, even if LumicyanoTM is sometimes less bright than the two-step process.
      Furthermore, conventional enhancement can still be carried out if needed. As a
      conclusion, LumicyanoTM makes it possible to avoid an enhancement step which can
      be detrimental to further examinations, particularly on rough or semi-porous
      surfaces.

PMID- 24314509
TI  - Differentiation of trifluoromethylbenzylpiperazines (TFMBZPs) and
      trifluoromethylbenzoylpiperazines (TFMBOPs) by GC-MS.
AB  - Two series of regioisomers - the trifluoromethylbenzylpiperazines (TFMBZPs) and
      the trifluoromethylbenzoylpiperazines (TMFBOPs) were synthesized and analyzed as
      potential "hybrid" derivatives of the benzylpiperazine (BZP) and 1-(3
      trifluoromethylphenyl)piperazine (TMFPP) drugs of abuse. The TFMBZPs are readily
      differentiated from TMFBOPs by their mass spectra including differences in their
      mass, the base peaks in their mass spectra as well as several other unique
      fragment ions. However the mass spectra of each regioisomer in each of these two
      series have fragment ions of identical mass and thus cannot be differentiated by
      this analytical method alone. Furthermore, chemical derivatization by
      perfluoroacylation did not offer any additional unique marker fragment ions in
      the mass spectrum to allow identification of one regioisomer in a series to the
      exclusion of the other two regioisomers. The perfluoroacylamides of the
      regioisomers in the TFMBZP series and the regioisomers in the TMFBOP series were
      readily separated by GC on the stationary phase Rtx-200 and eluted in an order
      similar to other perfluoroacyl-derivatives of other benzyl- and benzoylpiperazine
      compounds reported earlier. 

PMID- 24314510
TI  - Sex determination using discriminant analysis of the medial and lateral condyles
      of the femur in Koreans.
AB  - The proximal and distal parts of the femur show the differences between the
      sexes. Head diameter and the breadth of the epicondyle of the femur are known to
      distinguish males from females. The proximal end of the femur is studied to
      determine sex using discriminant analysis but; its distal end is not done. This
      study aims to develop an equation specific to Koreans by using the medial and
      lateral condyles of the femur, and to demonstrate the usefulness of equations for
      specific population groups. We used three-dimensional images from 202 Korean
      femurs. Twelve variables were measured with a computer program after the femurs
      were in alignment. Eleven variables showed a statistically significant difference
      between the sexes (P<0.01). The most accurate equation used width of the medial
      and lateral condyles (WDC), with of the medial condyle (WMC), depth of the
      lateral condyle (DLC), and depth of the intercondylar notch (DIN) (94.1%), and is
      as follows: D = 0.336 * WDC + (-0.097) * WMC + (-0.153) * DLC + 0.372 * DIN -
      20.912. The second highest accuracy was 90.1% for the width dimensional group and
      WDC. This study shows that the medial and lateral condyles of the femur should be
      helpful for sex determination in situations where the skull and pelvis are
      missing and part of the femur is available. The study also demonstrates the need
      for different equations for different population groups.

PMID- 24314511
TI  - Estimating daily and diurnal variations of illicit drug use in Hong Kong: a pilot
      study of using wastewater analysis in an Asian metropolitan city.
AB  - The measurement of illicit drug metabolites in raw wastewater is increasingly
      being adopted as an approach to objectively monitor population-level drug use,
      and is an effective complement to traditional epidemiological methods. As such,
      it has been widely applied in western countries. In this study, we utilised this
      approach to assess drug use patterns over nine days during April 2011 in Hong
      Kong. Raw wastewater samples were collected from the largest wastewater treatment
      plant serving a community of approximately 3.5 million people and analysed for
      excreted drug residues including cocaine, ketamine, methamphetamine, 3,4
      methylenedioxymethamphetamine (MDMA) and key metabolites using liquid
      chromatography coupled with tandem mass spectrometry. The overall drug use
      pattern determined by wastewater analysis was consistent with that have seen
      amongst people coming into contact with services in relation to substance use;
      among our target drugs, ketamine (estimated consumption: 1400-1600 mg/day/1000
      people) was the predominant drug followed by methamphetamine (180-200 mg/day/1000
      people), cocaine (160-180 mg/day/1000 people) and MDMA (not detected). The levels
      of these drugs were relatively steady throughout the monitoring period. Analysing
      samples at higher temporal resolution provided data on diurnal variations of drug
      residue loads. Elevated ratios of cocaine to benzoylecgonine were identified
      unexpectedly in three samples during the evening and night, providing evidence
      for potential dumping events of cocaine. This study provides the first
      application of wastewater analysis to quantitatively evaluate daily drug use in
      an Asian metropolitan community. Our data reinforces the benefit of wastewater
      monitoring to health and law enforcement authorities for strategic planning and
      evaluation of drug intervention strategies.

PMID- 24314512
TI  - Preliminary performance assessment of computer automated facial approximations
      using computed tomography scans of living individuals.
AB  - ReFace (Reality Enhancement Facial Approximation by Computational Estimation) is
      a computer-automated facial approximation application jointly developed by the
      Federal Bureau of Investigation and GE Global Research. The application derives a
      statistically based approximation of a face from a unidentified skull using a
      dataset of ~400 human head computer tomography (CT) scans of living adult
      American individuals from four ancestry groups: African, Asian, European and
      Hispanic (self-identified). To date only one unpublished subjective recognition
      study has been conducted using ReFace approximations. It indicated that
      approximations produced by ReFace were recognized above chance rates (10%). This
      preliminary study assesses: (i) the recognizability of five ReFace
      approximations; (ii) the recognizability of CT-derived skin surface replicas of
      the same individuals whose skulls were used to create the ReFace approximations;
      and (iii) the relationship between recognition performance and resemblance
      ratings of target individuals. All five skin surface replicas were recognized at
      rates statistically significant above chance (22-50%). Four of five ReFace
      approximations were recognized above chance (5-18%), although with statistical
      significance only at the higher rate. Such results suggest reconsideration of the
      usefulness of the type of output format utilized in this study, particularly in
      regard to facial approximations employed as a means of identifying unknown
      individuals.

PMID- 24314513
TI  - Application of MECC-DAD and CZE-MS to examination of color stamp inks for
      forensic purposes.
AB  - Questioned document examination in a wide variety of criminal and civil cases
      often focuses on the identification and comparison of stamp inks. Increasingly
      frequent counterfeiting of documents, especially those that have been stamped,
      has led to a growing need for instrumental methods that will allow an in-depth
      examination of stamp inks on a document. Therefore, the usefulness of two
      capillary electrophoresis techniques: micellar electrophoretic capillary
      chromatography with UV/Vis diode array detection (MECC-DAD) and capillary zone
      electrophoresis with electrospray mass spectrometric detection (CZE-ESI/MS) was
      verified for this purpose. Violet, red, blue and green stamp inks on paper
      surfaces were investigated. Electropherograms and mass spectra of inks purchased
      from 10 different producers were obtained in accordance with optimized and
      validated analytical procedures. It was shown that effective differentiation of
      individual inks was possible in terms of migration time and UV/Vis spectra
      provided that there was more than one characteristic peak. However, the most
      problematic inks with only one very similar (or identical) dye component - violet
      and blue ones - were additionally differentiated by CZE-MS. The obtained results
      showed that the proposed procedures can be useful for the objective analysis of
      questioned documents involving stamp inks. Consequently, the developed methods
      can be applied in the forensic field, including in the investigation of the
      authenticity of documents. 

PMID- 24314514
TI  - Electrothermic damage to the nail due to arcing in high-voltage discharge.
AB  - The burn effects in high-voltage electrocutions are manifold ranging from
      inconspicuous marks to deep charring. Apart from lesions caused by direct contact
      with a live conductor, the victim's body may suffer flash burns from arcing
      resulting in extensive scattered or confluent heat damage of the skin. In such
      cases, the nail plates of fingers and toes may undergo thermal changes which up
      to now have not been mentioned in the pertinent literature. Macroscopically, the
      nail shows a yellowish discoloration with tiny and closely arranged verruciform
      elevations. Histologically, the uppermost layer of the nail plate is interspersed
      with small vacuoles resembling micro-blisters as seen in the corneal layer of
      common electric marks. The surface of the nail is coated with a thin film of
      carbonaceous material. Based on an accidental high-voltage electrocution recently
      observed by the authors, attention is also drawn to the possible occurrence of
      contact burns from metal objects heated by the current as this finding is usually
      described only in victims of lightning strikes and not in the context of high
      voltage discharges of technical electricity. 

PMID- 24314515
TI  - Cardiac troponin T in forensic autopsy cases.
AB  - The aim of the present study was to describe the findings of postmortem serum and
      pericardial fluid (PF) cardiac troponin T (cTnT) in various causes of death with
      regard to the postmortem interval (PMI) and comorbid cardiovascular disease,
      using 101 autopsy cases with PMI of 8-141 h divided into 9 groups: cardiovascular
      disease (CVD), other diseases (OD), poisoning (P), asphyxia (A), drowning (D),
      hypothermia (H), thoracic trauma (TT), other trauma (OT) and fire fatalities (F).
      The results suggest that cTnT levels may help to differentiate cardiovascular
      death from poisoning and non-thoracic trauma, as well as to differentiate
      cardiovascular and other diseases as cause of death from drowning and
      hypothermia. However, the effect of PMI, unlike comorbid cardiovascular disease,
      has to be taken into account.

PMID- 24314516
TI  - Passive forensics for copy-move image forgery using a method based on DCT and
      SVD.
AB  - As powerful image editing tools are widely used, the demand for identifying the
      authenticity of an image is much increased. Copy-move forgery is one of the
      tampering techniques which are frequently used. Most existing techniques to
      expose this forgery need to improve the robustness for common post-processing
      operations and fail to precisely locate the tampering region especially when
      there are large similar or flat regions in the image. In this paper, a robust
      method based on DCT and SVD is proposed to detect this specific artifact.
      Firstly, the suspicious image is divided into fixed-size overlapping blocks and
      2D-DCT is applied to each block, then the DCT coefficients are quantized by a
      quantization matrix to obtain a more robust representation of each block.
      Secondly, each quantized block is divided non-overlapping sub-blocks and SVD is
      applied to each sub-block, then features are extracted to reduce the dimension of
      each block using its largest singular value. Finally, the feature vectors are
      lexicographically sorted, and duplicated image blocks will be matched by
      predefined shift frequency threshold. Experiment results demonstrate that our
      proposed method can effectively detect multiple copy-move forgery and precisely
      locate the duplicated regions, even when an image was distorted by Gaussian
      blurring, AWGN, JPEG compression and their mixed operations. 

PMID- 24314517
TI  - Diagnosis of drowning by summation of sodium, potassium and chloride ion levels
      in pleural effusion: differentiating between freshwater and seawater drowning and
      application to bathtub deaths.
AB  - Although electrolyte analysis of pleural effusion at autopsy is useful for the
      diagnosis of water aspiration (i.e., drowning), the method of comparing each
      level of sodium (Na(+)), potassium (K(+)), and chloride (Cl(-)) ions does not
      clearly differentiate between freshwater drowning, seawater drowning, and non
      drowning. Therefore, here we introduce the summation of Na(+), K(+), and Cl(-)
      levels, that is SUM(Na+K+Cl), as a modified diagnostic indicator. In 21 autopsy
      cases of freshwater drowning, 32 cases of seawater drowning, and 43 non-drowning
      controls (with pleural effusion), mean SUM(Na+K+Cl) differed significantly
      between the groups (188.8+/-33.2, 403.5+/-107.9, and 239.3+/-21.7 mEq/L,
      respectively). We defined a SUM(Na+K+Cl) cut-off value of <195.9 mEq/L as
      strongly suggestive of freshwater aspiration and that of >282.7 mEq/L as strongly
      suggestive of seawater aspiration. When these values were applied to the two
      drowning groups, 15 cases (71%) of freshwater drowning and 29 cases (91%) of
      seawater drowning were diagnosed correctly. This new approach may be more valid
      than previous methods in cases found >2 days after death or those with
      substantial pleural effusion (>100 mL). For an additional 15 bathtub deaths, mean
      SUM(Na+K+Cl) was 198.8+/-40.0 mEq/L, and in 14 of these cases (93%) the
      relationship between cause of death and SUM(Na+K+Cl) could be explained using
      this method. Forensic pathologists should not depend exclusively on chemical
      findings and should consider also typical pathological indicators of drowning.
      This new method may be useful as a supplementary diagnostic tool when used
      alongside consideration of the pathological findings.

PMID- 24314518
TI  - Trace detection of perchlorate in industrial-grade emulsion explosive with
      portable surface-enhanced Raman spectroscopy.
AB  - Recent analyses by ion-exchange chromatography (IC) showed that, beside nitrate,
      the majority of the industrial-grade emulsion explosives, extensively used by
      most separatists in the southern Thailand insurgency, contained small traces of
      perchlorate anions. In demand for the faster, reliable, and simple detection
      methods, the portable detection of nitrate and perchlorate became the great
      interest for the forensic and field-investigators. This work proposed a unique
      method to detect the trace amount of perchlorate in seven industrial-grade
      emulsion explosives under the field tests. We utilized the combination of the
      portable Raman spectroscope, the developed surfaced-enhanced Raman substrates,
      and the sample preparation procedures. The portable Raman spectroscope with a
      laser diode of 785 nm for excitation and a thermoelectric-cooled CCD spectrometer
      for detection was commercially available. The SERS substrates, with uniformly
      distributed nanostructured silver nanorods, were fabricated by the DC magnetron
      sputtering system, based on the oblique-angle deposition technique. The sample
      preparation procedures were proposed based on (1) pentane extraction technique
      and (2) combustion technique, prior to being dissolved in the purified water. In
      comparison to the ion chromatography and the conventional Raman measurements, our
      proposed methods successfully demonstrated the highly sensitive detectability of
      the minimal trace amount of perchlorate from five of the explosives with minimal
      operating time. This work was therefore highly practical to the development for
      the forensic analyses of the post-blast explosive residues under the field
      investigations.

PMID- 24314519
TI  - Example of human individual identification from World War II gravesite.
AB  - This paper presents the procedure elaborated by our team which was applied to the
      mode of identification of Red Army soldiers who were taken as prisoners by the
      German Army during World War II and deceased in captivity. In the course of our
      search the unmarked burial of ten Soviet prisoners of war was found. Historical,
      anthropological and genetic research conducted by us led to the personal
      identification of nine of them, including two by means of DNA analysis. 

PMID- 24314520
TI  - A robust color image watermarking technique using modified Imperialist
      Competitive Algorithm.
AB  - In this paper, a novel robust watermarking technique using Imperialistic
      Competition Algorithm (ICA) in the spatial domain is proposed to protect the
      intellectual property rights of color images. The proposed method tries to insert
      the watermark in the blocks which are selected by Modified ICA. In this method,
      ICA has been customized for watermarking. The color band for watermark insertion
      is selected based on color dynamic range in each block. Besides, in the procedure
      of selecting blocks for watermark insertion and extraction, ensuring higher
      fidelity and robustness and resilience to several possible image attacks have
      been considered. The experimental results showed that the proposed method
      performance created watermarked images with better PSNRs and more robustness
      versus several attacks such as additive noise and blurring in compare to related
      works. 

PMID- 24314521
TI  - Impact of reaction parameters on the chemical profile of 3,4
      methylenedioxymethamphetamine synthesized via reductive amination: target
      analysis based on GC-qMS compared to non-targeted analysis based on GC*GC-TOF-MS.
AB  - The most common clandestine manufacturing procedure for the ecstasy derivative
      3,4-methylenedioxymethamphetamine (MDMA), is the reductive amination of
      piperonylmethylketone (PMK) via platinum(IV) oxide/hydrogen. Deviations of the
      reaction conditions during the synthesis may result in different chemical
      profiles of the products. The chemical analysis of these profiles is an important
      objective for forensic drug intelligence. In this work we studied the impact of a
      systematic variation of the hydrogenation time, the reaction temperature and the
      precursor batch on the resulting organic chemical profiles of the MDMA bases and
      MDMA hydrochlorides. Target analysis was based on a gas chromatography mass
      spectrometry (GC-MS) method which was harmonized during the European project
      CHAMP.(2) In addition, samples were analyzed by comprehensive two-dimensional gas
      chromatography time-of-flight mass spectrometry (GC*GC-TOFMS) and subjected to
      non-targeted data analysis for a comprehensive analysis of the complete profiles.
      The reaction temperature, followed by the used precursor batch, revealed the
      highest impact on the chemical profile. The effect on individual impurity
      compounds is discussed in detail. With respect to the interpretation of the data,
      the profiles were compared to the profiles of MDMA samples obtained by reductive
      amination using sodium borohydride ("cold method") and aluminium/mercury amalgam
      as alternative reducing agents. Non-targeted analysis revealed that the
      discrimination according to the synthetic route and the batch of precursor used
      for the synthesis strongly depends on the selected target compounds. 

PMID- 24314522
TI  - The human DNA content in artifacts deposited by the blowfly Lucilia cuprina fed
      human blood, semen and saliva.
AB  - Adult flies of some species are known to be attracted to crime scenes where they
      feed on the proteinaceous decomposition products of dead bodies. The flies leave
      deposits through excretion and regurgitation, and these artifacts often appear
      morphologically similar to bloodstains. To date, little consideration has been
      given to the possibility of the fly artifacts containing forensically useful
      levels of human DNA, or of flies as vectors of human DNA. In the present study,
      groups of artifacts collected after the adult blowfly Lucilia cuprina fed on
      biological fluids were examined and found to contain human DNA sufficient for
      profiling. Random samples from each group of artifacts were then subjected to
      human DNA profiling. Of the samples analysed, full or partial human DNA profiles
      were found in 57% of samples deposited by flies after blood meals, 92% after
      semen meals, 46% after saliva meals, 93% after blood/semen meals, 58% after
      blood/saliva meals and 95% after semen/saliva meals. DNA from artifacts deposited
      after flies were fed blood, semen, saliva, blood/semen, blood/saliva or
      semen/saliva was extracted at various time points up to 750 days, and the human
      DNA component quantified. The human DNA extracted from blood- and semen-based fly
      artifacts demonstrated a clear trend in which the amount of DNA extracted
      increased over the first 400 days, and full human DNA profiles were still
      obtained 750 days after artifact deposition. Saliva- and blood/saliva-based
      samples were tested at intervals up to 60 days and generated partial profiles at
      this final time. Blood/semen- and semen/saliva-based samples generated full
      profiles at 250 days. The presence of human DNA in fly artifacts has considerable
      forensic significance. Fly artifacts could potentially compromise crime
      reconstruction, and/or contaminate DNA evidence, up to at least two years after
      their deposition. Alternatively, fly artifacts may be a useful source of DNA if
      an offender has attempted to clean up a crime scene. 

PMID- 24314523
TI  - Biomechanical analysis of skull fractures after uncontrolled hanging release.
AB  - In forensic research, biomechanical analyses of falls are widely reported.
      However, no study on falls consecutive to uncontrolled hanging release, when a
      hanging body is cut down, has ever been published. In such cases, the presence of
      cranial trauma can raise interpretation issues, and there may be doubt as to
      whether the fall was an accident or a crime disguised as suicide. The problem
      remains as to whether or not a fall after a free hanging release can lead to a
      skull fracture. To address this question, numerical simulations, post-mortem
      human subject tests and parametric studies were performed. We first recreated the
      kinematics and velocity of this atypical fall with post-mortem human subject
      tests and multibody simulations. We then tested the influence of biological
      variability on fracture production using a finite element model of the head. Our
      results show that fall severity depends largely on the direction of the fall. The
      risk of fracture is highest in the occipital region and with a backward fall. Our
      study also highlights the frequent occurrence of lower limb trauma in a free
      hanging release. Most importantly, we show that a fracture is produced in only
      3.4% of falls that occur in a 10-90 cm height range. The overall findings of this
      study provide tools for pathologists and magistrates to decide on the most likely
      scenario and to justify further forensic investigations if required.

PMID- 24314524
TI  - Timing of blunt force injuries in long bones: the effects of the environment, PMI
      length and human surrogate model.
AB  - Timing of blunt force trauma in human bone is a critical forensic issue, but
      there is limited knowledge on how different environmental conditions, the
      duration of postmortem interval (PMI), different bone types and different animal
      models influence fracture morphology. This study aims at evaluating the influence
      of the type of postmortem environment and the duration of the postmortem period
      on fracture morphology, for distinguishing perimortem from postmortem fractures
      on different types of long bones from different species. Fresh limb segments from
      pig and goat were sequentially left to decompose, under 3 different environmental
      circumstances (surface, buried and submerged), resulting in sets with different
      PMI lengths (0, 28, 56, 84, 112, 140, 168 and 196 days), which were then
      fractured. Fractured bones (total=325; pig tibia=110; pig fibula=110; goat
      metatarsals=105) were classified according to the Fracture Freshness Index (FFI).
      Climatic data for the experiment location was collected. Statistical analysis
      included descriptive statistics, correlation analysis between FFI and PMI, Mann
      Whitney U tests comparing FFI medians for different PMI's and linear regression
      analysis using PMI, pluviosity and temperature as predictors for FFI. Surface
      samples presented increases in FFI with increasing PMI, with positive
      correlations for all bone types. The same results were observed in submerged
      samples, except for pig tibia. Median FFI values for surface samples could
      distinguish bones with PMI=0 days from PMI>=56 days. Buried samples presented no
      significant correlation between FFI and PMI, and nonsignificant regression
      models. Regression analysis of surface and submerged samples suggested
      differences in FFI variation with PMI between bone types, although without
      statistical significance. Adding climatic data to surface regression models
      resulted in PMI no longer predicting FFI. When comparing different animal models,
      linear regressions suggested greater increases in FFI with increasing PMI in pig,
      compared to goat, in both surface and submerged environments, although
      statistically not significant. No differences were found between environments
      except for buried vs. submerged goat samples and surface vs. buried/submerged
      tibia pig samples. FFI showed a weak association with PMI and it seems to be
      affected by various factors, such as different bone types, decomposition
      environments and climatic factors. Nonetheless, the FFI shows promising
      discriminating power during the early postmortem period. The apparent variation
      between bone types from different species suggests that extrapolations to humans
      can be challenging.

PMID- 24314525
TI  - Comprehensive methodology for identification of Kratom in police laboratories.
AB  - Leaves of Mitragyna speciosa Korth (Rubiaceae), commonly known as Kratom, are a
      popular narcotic product among recreational users all over the world. This
      product is widely distributed on the Internet and via smart-shops and is often a
      subject of examination in police laboratories. A major psychoactive component of
      Kratom is mitragynine which occurs exclusively in this species. The variety of
      combinations among M. speciosa products, cases of plant or chemical composition
      adulteration, give rise to a need to develop an universal methodology for
      identification of both, plant material and its active metabolite, mitragynine.
      Herein we propose a comprehensive authentication procedure which involves the
      microscopic analysis of plant material and inexpensive mitragynine detection
      using thin layer chromatography (TLC) and high performance liquid chromatography
      (HPLC). The developed methodology was successfully applied for the plant material
      investigation. Five samples of dried, shredded or powdered Kratom leaves,
      purchased via the Internet and one sample delivered by police have been
      identified. 

PMID- 24314526
TI  - Digital forensics: an analytical crime scene procedure model (ACSPM).
AB  - In order to ensure that digital evidence is collected, preserved, examined, or
      transferred in a manner safeguarding the accuracy and reliability of the
      evidence, law enforcement and digital forensic units must establish and maintain
      an effective quality assurance system. The very first part of this system is
      standard operating procedures (SOP's) and/or models, conforming chain of custody
      requirements, those rely on digital forensics "process-phase-procedure-task
      subtask" sequence. An acceptable and thorough Digital Forensics (DF) process
      depends on the sequential DF phases, and each phase depends on sequential DF
      procedures, respectively each procedure depends on tasks and subtasks. There are
      numerous amounts of DF Process Models that define DF phases in the literature,
      but no DF model that defines the phase-based sequential procedures for crime
      scene identified. An analytical crime scene procedure model (ACSPM) that we
      suggest in this paper is supposed to fill in this gap. The proposed analytical
      procedure model for digital investigations at a crime scene is developed and
      defined for crime scene practitioners; with main focus on crime scene digital
      forensic procedures, other than that of whole digital investigation process and
      phases that ends up in a court. When reviewing the relevant literature and
      interrogating with the law enforcement agencies, only device based charts
      specific to a particular device and/or more general perspective approaches to
      digital evidence management models from crime scene to courts are found. After
      analyzing the needs of law enforcement organizations and realizing the absence of
      crime scene digital investigation procedure model for crime scene activities we
      decided to inspect the relevant literature in an analytical way. The outcome of
      this inspection is our suggested model explained here, which is supposed to
      provide guidance for thorough and secure implementation of digital forensic
      procedures at a crime scene. In digital forensic investigations each case is
      unique and needs special examination, it is not possible to cover every aspect of
      crime scene digital forensics, but the proposed procedure model is supposed to be
      a general guideline for practitioners. 

PMID- 24314527
TI  - Determining the effects of routine fingermark detection techniques on the
      subsequent recovery and analysis of explosive residues on various substrates.
AB  - An offender who has recently handled bulk explosives would be expected to deposit
      latent fingermarks that are contaminated with explosive residues. However,
      fingermark detection techniques need to be applied in order for these fingermarks
      to be detected and recorded. Little information is available in terms of how
      routine fingermark detection methods impact on the subsequent recovery and
      analysis of any explosive residues that may be present. If an identifiable
      fingermark is obtained and that fingermark is found to be contaminated with a
      particular explosive then that may be crucial evidence in a criminal
      investigation (including acts of terrorism involving improvised explosive
      devices). The principal aims of this project were to investigate: (i) the typical
      quantities of explosive material deposited in fingermarks by someone who has
      recently handled bulk explosives; and (ii) the effects of routine fingermark
      detection methods on the subsequent recovery and analysis of explosive residues
      in such fingermarks. Four common substrates were studied: paper, glass, plastic
      (polyethylene plastic bags), and metal (aluminium foil). The target explosive
      compounds were 2,4,6-trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN),
      and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), as well as chlorate and
      nitrate ions. Recommendations are provided in terms of the application of
      fingermark detection methods on surfaces that may contain explosive residues. 

PMID- 24314528
TI  - Female sexual homicide offenders: an analysis of the offender racial profiles in
      offending process.
AB  - Despite the recent effort by Chan and Frei in studying female sexual homicide
      offenders (SHOs), much is still unknown about this underresearched offender
      population. One largely unexplored area is how female SHOs of different races
      commit their killings. Using FBI Supplemental Homicide Reports (SHR) data (1976
      2007), 105 White and 94 Black female SHOs (N=204) were examined for their
      differential offending patterns. Most female SHOs, regardless of race, killed
      victims of the opposite gender (i.e., heterosexual offenses). Most frequently
      targeted by female SHOs of both races (44% of Whites and 57% of Blacks) were
      known victims (e.g., friends, acquaintances) who were not intimate partners or
      family members. Firearms were the most common weapons used by female SHOs (60% of
      Whites and 48% of Blacks). The second most common weapon type used by Black
      offenders was an edged weapon (32%), whereas for White offenders it was a
      personal weapon (17%). Black female SHOs normally perpetrated their offense in
      large cities (69%), while White female SHOs most often committed their crime in
      suburban areas (40%). This study underscores importance of considering the
      offender racial group in female sexual murder investigations. Hence, several
      implications for offender profiling are offered.

PMID- 24314529
TI  - Suicide among male prisoners in France: a prospective population-based study.
AB  - BACKGROUND: Suicide rates are high among prisoners but little is known about the
      precise weight of each risk factor. METHODS: We collected data on the periods of
      imprisonment of all adult males incarcerated in France between 1 January, 2006
      and 15 July, 2009. We used survival analyses from the incarceration to its end,
      censored by the observation period. We calculated suicide rates and performed a
      Cox model to assess the link between prisoners' imprisonment characteristics and
      suicide risk. RESULTS: Overall, 301,611 periods of imprisonment were observed and
      353 suicides were recorded. The suicide rate was 17.9 suicides per 10,000 person
      years (95% CI: 16.1-19.9). The hazard ratio (HR) of suicide risk was high for
      placements in a disciplinary cell (15.7, 95% CI: 10.6-23.5) and varied depending
      on the main offence (homicide: 7.6, 95% CI: 5.3-10.9, rape: 4.6, 95% CI: 3.2-6.6,
      other sexual assault: 2.9, 95% CI: 1.9-4.6, other violent offence: 2.1, 95% CI:
      1.5-2.8, compared with other offences). HR was lower when visits from relatives
      were observed (0.4, 95% CI: 0.3-0.5) and higher if a hospitalization was observed
      (1.6, 95% CI: 1.3-2.0). After conviction, HR halved with respect to the remand
      period, but there was no difference by sentence length. HR was higher if
      incarceration occurred after age 30 (1.4, 95% CI: 1.1-1.7). Foreigners tended to
      have lower risks than French prisoners, with the exception of those incarcerated
      for rape. CONCLUSIONS: The suicide rate in prison is generally much higher than
      in the general population. This study has replicated previous international
      findings, highlighting the impact of the type of offence on suicide risk. Suicide
      prevention programmes must consider the high risk associated with incarceration
      for a criminal offence against a person. With regard to the impact of visits from
      relatives and placements in a disciplinary cell, further work should be conducted
      from a psychological perspective to examine the effects of physical and social
      isolation.

PMID- 24314530
TI  - Breath alcohol elimination rate as a function of age, gender, and drinking
      practice.
AB  - The objective of this study was to determine whether breath alcohol elimination
      rate varies as a function of age, gender, and drinking practice, factorially
      combined. Eighty-four men and 84 women drank enough alcohol to produce peak BrACs
      of .110 g/210 L for heavy and moderate drinkers and BrACs of .090 g/210 L for
      light drinkers. An Intoxilyzer 5000 was used to generate the concentration-time
      profiles. Mean (M) elimination rates (g/210 L/h) were found to be higher for
      women (N=84, M=.0182, SD=.0033) than for men (N=84, M=.0149, SD=.0029), F(1,
      144)=57.292, p<.001; higher for heavy drinkers (N=56, M=.0176, SD=.0038) than for
      light and moderate drinkers combined (N=112, M=.0160, SD=.0032), F(1,
      144)=12.434, p<.01; and higher for older subjects (51-69 years, N=42, M=.0180,
      SD=.0038) than younger subjects (19-50 years, N=126, M=.0161, SD=.0033), F(1,
      144)=14.324, p<.001. None of the two-way interactions (age * gender, age *
      drinking practice, gender * drinking practice) or the three-way interaction (age
      * gender * drinking practice) was statistically significant. Limitations of the
      current study and suggestions for further research are discussed.

PMID- 24314531
TI  - Effect of laundering on visible damage to apparel fabric caused by sharp force
      impact.
AB  - Sharp force violence is a common way of committing assault in numerous countries
      and regions around the world. When a stabbing occurs, the clothing worn by the
      victim may provide vital evidence: for example the weapon used to stab the victim
      may be identified from severance in the clothing. However, whether laundering the
      clothing after an attack affects the severance morphology of the fabric and
      fibres, and whether identification of the weapon is possible from the severance
      in the clothing after laundering is not known. This study focussed on the effect
      of laundering 100% cotton twill weave (drill) and single jersey (knit) fabrics.
      Specimens had been pre-treated and stabbed with either a kitchen knife or a
      Phillips screwdriver. These specimens were photographed and were again laundered
      for one wash cycle before being photographed again. Ten expert judges compared
      the photographs taken before and after laundering. A difference in the appearance
      of the fabrics before and after laundering was evident. The morphology of the
      fabric and fibres thus would be expected to differ after laundering the clothing,
      making identification of a weapon used to stab through clothing more difficult. 

PMID- 24314532
TI  - Age estimation of bloodstains using smartphones and digital image analysis.
AB  - Recent studies on bloodstains have focused on determining the time since
      deposition of bloodstains, which can provide useful temporal information to
      forensic investigations. This study is the first to use smartphone cameras in
      combination with a truly low-cost illumination system as a tool to estimate the
      age of bloodstains. Bloodstains were deposited on various substrates and
      photographed with a smartphone camera. Three smartphones (Samsung Galaxy S Plus,
      Apple iPhone 4, and Apple iPad 2) were compared. The environmental effects -
      temperature, humidity, light exposure, and anticoagulant - on the bloodstain age
      estimation process were explored. The color values from the digital images were
      extracted and correlated with time since deposition. Magenta had the highest
      correlation (R(2)=0.966) and was used in subsequent experiments. The Samsung
      Galaxy S Plus was the most suitable smartphone as its magenta decreased
      exponentially with increasing time and had highest repeatability (low variation
      within and between pictures). The quantifiable color change observed is
      consistent with well-established hemoglobin denaturation process. Using a
      statistical classification technique called Random ForestsTM, we could predict
      bloodstain age accurately up to 42 days with an error rate of 12%. Additionally,
      the age of forty blind stains were all correctly predicted, and 83% of mock
      casework samples were correctly classified. No within- and between-person
      variations were observed (p>0.05), while smartphone camera, temperature,
      humidity, and substrate color influenced the age determination process in
      different ways. Our technique provides a cheap, rapid, easy-to-use, and truly
      portable alternative to more complicated analysis using specialized equipment,
      e.g. spectroscopy and HPLC. No training is necessary with our method, and we
      envision a smartphone application that could take user inputs of environmental
      factors and provide an accurate estimate of bloodstain age. 

PMID- 24314534
TI  - Direct determination of diazepam and its glucuronide metabolites in human whole
      blood by MUElution solid-phase extraction and liquid chromatography-tandem mass
      spectrometry.
AB  - A MUElution solid-phase extraction (SPE) liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for simultaneous determination of diazepam,
      nordiazepam, oxazepam, oxazepam glucuronide, temazepam and temazepam glucuronide
      in human whole blood is presented. 200 MUL of whole blood samples were loaded
      onto a Waters Oasis HLB 96-well MUElution SPE plate using 75 MUL of methanol as
      the elution solvent, and the eluents were injected into an Eclipse XDB C18
      column. No hydrolysis, solvent transfer, evaporation or reconstitution was
      involved in the sample preparation procedures. Tandem mass spectrometric
      detection with Turbo Ion Spray was conducted via multiple reaction monitoring
      (MRM) under positive ionization mode. The method was validated and proved to be
      accurate (accuracy within 93-108%), precise (intra-day RSD<9.9% and inter-day
      RSD<7.2%) and sensitive with limits of detection (LOD) in the range of 0.05-0.25
      ng/mL for all the compounds. Extraction recoveries were in the range of 31-80%
      for all the analytes. This method demonstrated to be reproducible and reliable.
      The applicability of the method was demonstrated by analysis of several forensic
      cases involving diazepam and its metabolites.

PMID- 24314533
TI  - The value of post-mortem CT in neonaticide in case of severe decomposition:
      description of 12 cases.
AB  - INTRODUCTION: In cases of neonaticide with delayed finding of the body,
      interpretation of autopsy results can be difficult because of decomposition.
      Postmortem computed tomography (PMCT) has become an increasingly popular tool in
      the (pediatric) forensic field. We performed a retrospective study to compare the
      outcome of PMCT with autopsy results in suspected neonaticide, in neonates found
      more than one week after their demise. We compared the performance of both
      methods on (1) determining gestational age, (2) differentiating between live
      birth and still birth and (3) determining cause of death. METHOD: We selected all
      consecutive neonaticide cases with an estimated postmortem interval longer than
      one week, who underwent a forensic autopsy including a total body PMCT in the
      Netherlands Forensic Institute in the period 2008-2012. Both a pathologist and
      radiologist scored gestational age, signs of live birth and cause of death for
      each case. RESULTS: 22 cases of neonaticide were identified in the study period,
      of which 15 cases were estimated to be found more than 1 week after death. In 12
      of these a total body PMCT was performed. In all cases, late postmortem changes
      were present. Gestational age could be assessed with PMCT in 100% of the cases
      and with autopsy in 58% of the cases. In all cases neither PMCT nor autopsy was
      able to assess live birth and cause of death. CONCLUSION: PMCT is a better tool
      for estimating gestational age in case of suspected neonaticide with late
      postmortem changes compared to autopsy and should therefore be a standard part of
      the work-up. Signs of live birth and cause of death could not be determined with
      neither of the methods, an adjusted post mortem examination including limited
      autopsy for these cases might be developed.

PMID- 24314535
TI  - Toxicological analysis of formalin-fixed or embalmed tissues: a review.
AB  - During the autopsy of forensic cases, when there is no suspicion of drug use or
      chemical exposure, biological fluids may not be obtained for toxicological
      analysis, while specimens of tissues may be collected and preserved in a formalin
      solution for histological examination. When specific questions arise after the
      burial, the only possible options are the exhumation of an embalmed body or the
      toxicological analysis of the formalin-fixed specimens. The drug concentrations
      in these specimens can be altered due to the extraction efficiency and/or the
      chemical activity of the formalin solutions used during chemical fixation or
      embalming process. The aim of this paper is to review the published studies about
      the determination of specific groups of drugs in formalin-fixed or embalmed
      specimens and their stability after chemical fixation or embalming process. The
      analytical aspects of this determination are also discussed. The stability of
      drugs in formalin environment and the possible reaction of the drugs with
      formaldehyde, which is a highly reactive chemical substance, should always be
      considered during post-mortem/post-embalming forensic analysis. The additional
      analysis of the formalin solution in which the tissue was preserved is considered
      necessary. The identification and the evaluation of the possible degradation
      products or chemical derivatives are extremely useful during the interpretation
      of the results. 

PMID- 24314536
TI  - Analysis of UR-144 and its pyrolysis product in blood and their metabolites in
      urine.
AB  - UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone] is a
      synthetic cannabinoid, which has been detected in many herbal blends, resinous
      samples and powders seized from the Polish drug market since the beginning of
      2012. This paper presents the case of intoxication by this substance. A complete
      picture of the symptoms observed by a witness, paramedics and medical doctors are
      given. In the analysis of powder residues from the plastic bag seized from the
      intoxicated person by gas chromatography-mass spectrometry (GC-MS), UR-144 and
      its major pyrolysis product [1-(1-pentyl-1H-indol-3-yl)-3-methyl-2-(propan-2
      yl)but-3-en-1-one] were detected. Both substances were also identified in a blood
      sample collected on admission of the patient to hospital using liquid
      chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS). Blood
      concentration of UR-144 was 6.1 ng/mL. A urine sample collected at the same time
      was analyzed by liquid chromatography-quadruple time-of-flight tandem mass
      spectrometry (LC-QTOF-MS). The parent substance and its pyrolysis products were
      not detected in urine, while their five metabolites were found. The experiments
      allowed the location of derivative groups to be established, and thus elucidate
      rough structures of the metabolites; a dihydroxylated metabolite of UR-144 and
      mono-, dihydroxylated and carboxylated metabolites of its pyrolysis product were
      identified.

PMID- 24314537
TI  - Post-mortem vitreous humour as potential specimen for detection of insulin
      analogues by LC-MS/MS.
AB  - Differentiation of insulin analogues is required in forensic and clinical
      toxicology as well as in sports doping control. Immunoassay results provide only
      weak evidence for exogenous administration of insulin, as concentrations cannot
      be reliably interpreted and specific information on the insulin species remains
      unknown. In post-mortem blood, insulin degrades rapidly. In this study, improved
      methodology consisting of precipitation of proteins, immunoaffinity purification
      and liquid chromatography coupled to high resolution/high accuracy mass
      spectrometry were applied to post-mortem vitreous humour. Ten successive cases
      with a post-mortem interval from four to ten days were investigated for insulin
      analogues. The cause of death in these cases was connected with diabetes and its
      complications, as well as with chronic cardiovascular disease, alcoholism and
      cancer. In all cases, the manner of death was natural (disease). Insulin was
      positively detected in post-mortem vitreous humour in three cases out of ten by
      mass spectrometry. In two cases, the method revealed the long-acting insulin
      glargine (Lantus) metabolite M2 (DesB31-32 Lantus), and human insulin was
      detected in one case. The findings were in agreement with the documented history
      of insulin medication. No other obvious reason could be found for the failure of
      detecting insulins in the other cases than insulin degradation during the lengthy
      post-mortem interval. Vitreous humour is still a most prospective specimen for
      detection of insulin analogues post-mortem. 

PMID- 24314538
TI  - Deaths from recreational use of propofol in Korea.
AB  - Propofol, a short-acting and sedative-hypnotic agent, induces and maintains
      anesthesia. Since it is known to produce mild euphoria and hallucinations, the
      recreational use of propofol has been a big issue in Korea. Furthermore, many
      deaths have occurred due to its abuse and misuse. In order to study the
      prevalence of abuse and deaths due to propofol, all autopsy cases conducted
      between 2005 and 2010 at the NFS (National Forensic Service, Korea) were
      monitored by checking its concentrations in the blood. Propofol was detected in
      131 cases (0.88%) out of 14,673 autopsied cases within 6 years. Propofol alone
      was detected in 49 of 131 fatal cases, while the combination of drugs was
      detected with propofol in the remaining 82 cases. The concentrations of propofol
      from autopsied cases ranged from 0.05 to 8.83 mg/L (mean 1.66; median 0.9) and
      from 0.08 to 8.65 mg/L (mean 1.71; median 1.05) in the heart (n=31) and the
      femoral blood (n=32), respectively. The investigation of the ratio of heart to
      femoral blood and the difference between the concentrations in heart and femoral
      blood (n=15) from the same body revealed the ratio from 0.45 to 3.66 (mean 1.53;
      median 1.40). The autopsy resulted in accidental death after self-administration
      in 16 autopsied cases among 131 autopsied cases. In 16 cases, their ages ranged
      from 17 to 56 and 75% of them were in their 20's and 30's and 75% were female.
      Half of them were medical personnel including 19% of doctors and 38% of nurses.
      The combination of drugs was detected in 6 cases. Fluoxetine was detected in
      three and vecuronium was detected in two along with propofol. The cause of death
      in 14 cases was drug intoxication, while that in 2 cases was hanging. Due to its
      prevalence, Korea has become the first country that regulates propofol as a
      psychotropic substance.

PMID- 24314539
TI  - Forensic signatures for Marburgviruses.
AB  - Marburgvirus is one of the most important hemorrhagic fever viruses with
      extremely high infectivity and fatality rate (~90%). It is transmitted easily in
      human populations through a respiratory route and therefore considered as a major
      biothreat agent. Although detection assays have been developed, no assay is
      available for forensic analysis. Here we report development of forensic assays
      for Marburgvirus. We performed detailed phylogenetic analysis of strains and
      isolates from all known Marburg virus outbreaks as well as from several
      laboratory strains and identified canonical SNPs for all major clades (outbreaks)
      and strains. TaqMan-MGB allelic discrimination assays targeting these SNPs were
      designed and experimentally screened against synthetic RNA templates and genomic
      RNAs. A total of 45 assays were validated to provide 100% coverage of the clades
      (outbreaks) and 91% at the strain level (21 out of the 23 targeted Marburgvirus
      strains) with built-in redundancy for increased robustness. Using these validated
      assays, we were able to provide accurate forensic analysis on 3 "unknown"
      Marburgviruses. These high-resolution forensic assays allow rapid and accurate
      genotyping of Marburgviruses for forensic investigations.

PMID- 24314540
TI  - Forensic analysis of ocular injuries during the 2011 revolution in Egypt.
AB  - INTRODUCTION: During the year 2011 the Egyptian revolution arose with a change in
      the trend of eye trauma in Egypt. AIM OF WORK: This study aims at reviewing the
      epidemiology of ocular trauma presenting to Ain Shams University teaching
      hospital during the year 2011 and comparing it with epidemiology during the
      previous 5 years. PATIENTS AND METHODS: This is a retrospective epidemiological
      and clinical study of patients admitted to Ain Shams University Hospital with
      ocular trauma from 2006 till 2011. Cases were analyzed with respect to age, sex,
      occupation, admission interval, type, mode, time and place of injury, causative
      instrument, diagnosis and examination findings, investigations, management and
      visual outcomes. RESULTS: Total numbers of cases presenting during the year 2011
      was 237 cases. The mean age was 22.5 years. Students (47.2%) and jobless people
      (21.9%) constituted the majority of the sample. During the year 2011 there was a
      significant increase in the percentage of injuries occurring in the street. There
      was also a significant rise in the percentage of homicidal ocular injuries
      specially those caused from non-rifled weapons. Fourteen cases of endophthalmitis
      were associated with non-rifled fire arm missiles while 7 were associated with
      glass intra-ocular foreign body. This indicated that the probability of
      occurrence of endophthalmitis with metal intraocular foreign bodies was 2:3 i.e.
      66.6% where as in glass intra ocular foreign body was 7:9 i.e. 77.7%. CONCLUSION:
      The majority of ocular trauma in our population during the year 2011 was due to
      homicidal street injuries occurring mainly in males of young age group, which is
      consistent with the events occurring in Egypt in this year. The findings indicate
      that ocular trauma is a significant cause of visual loss in this population.

PMID- 24314541
TI  - The forensic analysis of office paper using carbon isotope ratio mass
      spectrometry. Part 3: Characterizing the source materials and the effect of
      production and usage on the delta13C values of paper.
AB  - When undertaking any study of the isotope abundance values of a bulk material,
      consideration should be given to the source materials and how they are combined
      to reach the final product being measured. While it is demonstrative to measure
      and record the values of clean papers, such as the results published as part one
      of this series, the majority of forensic casework samples would have undergone
      some form of writing or printing process prior to examination. Understanding the
      effects of these processes on the delta(13)C values of paper is essential for
      interpretation and comparison with clean samples, for example in cases where
      printed documents need to be compared to paper from an unprinted suspect ream.
      This study was undertaken so that the source materials, the effects of the
      production process and the effects of printing and forensic testing could be
      observed with respect to 80 gsm white office papers. Samples were taken
      sequentially from the paper production facility at the Australian Paper Mill
      (Maryvale, VIC). These samples ranged from raw wood chips through the pulping,
      whitening and refinement steps to the final formed and packed paper. Cellulose
      was extracted from each sample to observe both fractionation and mixing steps and
      their effect on the delta(13)C values. Overall, the mixing steps were observed to
      have a larger effect on the isotopic values of the bulk materials than any
      potential fractionation. Printing of papers using toner and inkjet printing
      processes and forensic testing were observed to have little effect on delta(13)C.
      These experiments highlighted considerations for sampling and confirmed the need
      for a holistic understanding of sample history to inform the interpretation of
      results.

PMID- 24314542
TI  - Analysis of household ignitable liquids and their post-combustion weathered
      residues using compound-specific gas chromatography-combustion-isotope ratio mass
      spectrometry.
AB  - The continuing rise in home and vehicular arson cases involving the use of
      ignitable liquids continues to be an area of concern for criminal and civil
      investigators. In this study, the compound-specific delta(13)C values of various
      components of four flammable household chemicals were measured using a single
      quadrupole mass spectrometer and an isotope ratio mass spectrometer as
      simultaneous detectors for a gas chromatograph. Whereas compound-specific carbon
      isotope ratios were able to discriminate between different sources of neat (pre
      combustion) ignitable liquids, analyses of the post-combustion residues were
      problematic. Weathering caused by combustion resulted in a significant increase
      in the (13)C content of specific peaks relative to the neat liquids (i.e. less
      negative delta values) such that the isotopic comparison of pre- and post
      combustion residues resulted in fractionation ranging from 0 to +100/00. Because
      of the current lack of understanding of isotopic fractionation during combustion,
      and because of problems encountered with co-elution in the more complex samples,
      compound-specific IRMS does not appear to be suitable for fire debris analysis.
      The comparison of non-combusted or non-weathered ignitable liquids is much more
      reliable, especially for relatively simple mixtures, and is best suited for
      exclusionary purposes until such time as a comprehensive database of samples is
      developed. Without a measure of the population variance, one cannot presently
      predict the false positive identification rate for the comparison of two
      ignitable liquids; i.e. the probability that two random ignitable liquid samples
      have indistinguishable isotope ratios. 

PMID- 24314544
TI  - Sarconesiopsis magellanica (Diptera: Calliphoridae) life-cycle, reproductive and
      population parameters using different diets under laboratory conditions.
AB  - Sarconesiopsis magellanica is a forensically relevant necrophagous blowfly that
      can aid in determining the post-mortem interval (PMI) as it is the first to
      colonise decomposing corpses. The blowfly has been reported in several South
      American countries including Colombia, in high-altitude regions ranging from 1200
      to 3100 m above sea level. The present study reports this blowfly's life cycle
      and an analysis of its reproductive and population parameters under laboratory
      conditions for the first time. Six successive generations of flies were produced
      with an average of 65.38% adults emerging with respect to the total number of
      puparia. The shortest life cycle from egg to adult emergence was found in
      individuals fed on a lyophilised liver (LL) diet, while the longest one was found
      in individuals fed with an egg-powdered milk (E-PM) diet; intermediate values
      were found when the pig liver (PL) diet was tested. The greatest adult longevity
      was achieved when the PL diet was used, the LL diet giving the shortest. The
      population parameters based on the horizontal life table were: net reproductive
      rate (Ro)=447.752+/-9.9, mean generational time (Tc)=18.18+/-0.38, natural
      population increase rate (r(m))=0.145 and finite population increase rate
      (lambda)=1.398. This blowfly colony represents a valuable asset for both basic
      and applied studies. Members of the S. magellanica colony so established were
      used for analysing the life-cycle, reproductive and population parameters, and
      further medical and forensic application studies are currently underway.

PMID- 24314543
TI  - The development of Protophormia terraenovae (Robineau-Desvoidy) at constant
      temperatures and its minimum temperature threshold.
AB  - The immature development of the forensically important blow fly Protophormia
      terraenovae (Robineau-Desvoidy) (Diptera: Calliphoridae) was observed at a range
      of constant temperatures: 9.8, 11, 13, 15, 20, 25, 28, 30, and 32 degrees C, and
      the minimum developmental times and mode of development to reach each stage were
      recorded. A comparison of the actual minimum temperature threshold was made to
      findings from linear extrapolation. The minimum temperature thresholds for the
      1st, 2nd and 3rd instars fell within 9.8 and 11 degrees C and those of the post
      feeding, pupal and adult stages fell within the range of 11-13 degrees C.
      However, in all cases the actual minimum temperature thresholds were greatly
      underestimated by the linear method. 

PMID- 24314545
TI  - The Pabst's method: an effective and low-budget tool for the forensic comparison
      of opaque thermoplastics--part 1: Additional discrimination of black electrical
      tapes.
AB  - For many years now, Pabst's micro-press has been used in German forensic science
      laboratories as a valuable addition to methods of comparative analysis of plastic
      trace evidence. However, it is as yet hardly known in laboratories outside of
      Germany. The principal reproducibility is demonstrated by a homogeneity check of
      a raw backing material of defined origin. The illustrated results of a
      proficiency test emphasise the applicability of the Pabst method for forensic
      comparisons. The discrimination power of the Pabst method was tested by taking 90
      black PVC-backings provided by the FBI Laboratory, i.e. those that could not be
      discriminated by standard methods. In this way further discriminations could be
      achieved. In the following, the Pabst method is therefore introduced as a
      straightforward, inexpensive and useful tool. 

PMID- 24314546
TI  - Forensic age estimation based on the trabecular bone changes of the pelvic bone
      using post-mortem CT.
AB  - We analyzed the trabecular bone changes in the pubic bone (PB) and in the
      auricular surface (AS) of the ilium using 319 CT scans of cadavers to estimate
      the age. Although the sharpness of the trabecular structure decreases in CT
      images when soft tissues are present, we identified four phases for the changes
      in PB and five in AS; a juvenile trait in PB and a senile trait in AS helped
      narrow the age range. High correlation with age was identified for both sexes in
      PB (F 0.89; M 0.75) and in AS (F 0.85; M 0.71) used independently or combined (F
      0.91; M 0.78). The old adults (>60 years) could be evaluated with better accuracy
      and discriminated in several phases. We found low inter-observer error and low
      inaccuracy (about 6 years, mean for all age ranges). The method is robust with
      respect to slice thickness, display window and kernel within the tested ranges. 

PMID- 24314547
TI  - Organic matter characterization of sediments in two river beaches from northern
      Portugal for forensic application.
AB  - In a forensic investigation, the analysis of earth materials such as sediments
      and soils have been used as evidence at a court of law, relying on the study of
      properties such as color, particle size distribution and mineral identification,
      among others. In addition, the analysis of the organic composition of sediments
      and soils is of particular value, since these can be used as complementary
      independent evidence to the inorganic component. To investigate the usefulness of
      organic indicators in sediment characterization and discrimination, seventy-seven
      samples were collected during a period of one year in two river beaches located
      at the southern bank of the Douro River estuary in the North of Portugal.
      Isotopes of total carbon, pollen and plant wax-marker analyses were performed. In
      both beaches, an increase of the organic matter concentrations was noticeable,
      moving landward, related with the higher cover of associated plant material. The
      results obtained showed that the combination of all the techniques adopted showed
      a clear discrimination between samples from the two beaches, and also showed a
      differentiation of samples in relation to distance from the river in both
      beaches. The results also show that seasonality in these beaches was not a
      determining factor for discrimination, at the times considered. In addition, the
      effects of time was not marked. 

PMID- 24314548
TI  - Forensic investigation of K2, Spice, and "bath salt" commercial preparations: a
      three-year study of new designer drug products containing synthetic cannabinoid,
      stimulant, and hallucinogenic compounds.
AB  - New designer drugs such as K2, Spice, and "bath salts" present a formidable
      challenge for law enforcement and public health officials. The following report
      summarizes a three-year study of 1320 law enforcement cases involving over 3000
      products described as vegetable material, powders, capsules, tablets, blotter
      paper, or drug paraphernalia. All items were seized in Arkansas from January 2010
      through December 2012 and submitted to the Arkansas State Crime Laboratory for
      analysis. The geographical distribution of these seizures co-localized in areas
      with higher population, colleges, and universities. Validated forensic testing
      procedures confirmed the presence of 26 synthetic cannabinoids, 12 designer
      stimulants, and 5 hallucinogenic-like drugs regulated by the Synthetic Drug
      Prevention Act of 2012 and other state statutes. Analysis of paraphernalia
      suggests that these drugs are commonly used concomitantly with other drugs of
      abuse including marijuana, MDMA, and methamphetamine. Exact designer drug
      compositions were unpredictable and often formulated with multiple agents, but
      overall, the synthetic cannabinoids were significantly more prevalent than all
      the other designer drugs detected. The synthetic cannabinoids JWH-018, AM2201,
      JWH-122, JWH-210, and XLR11 were most commonly detected in green vegetable
      material and powder products. The designer stimulants methylenedioxypyrovalerone
      (MDPV), 3,4-methylenedioxy-N-methylcathinone (methylone), and alpha-methylamino
      valerophenone (pentedrone) were commonly detected in tablets, capsules, and
      powders. Hallucinogenic drugs were rarely detected, but generally found on
      blotter paper products. Emerging designer drug products remain a significant
      problem and continued surveillance is needed to protect public health. 

PMID- 24314550
TI  - Estimation of SNP heritability from dense genotype data.

PMID- 24314549
TI  - Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes
      for CVD risk traits.
AB  - Cardiovascular disease (CVD) affects millions of people worldwide and is
      influenced by numerous factors, including lifestyle and genetics. Expression
      quantitative trait loci (eQTLs) influence gene expression and are good candidates
      for CVD risk. Founder-effect pedigrees can provide additional power to map genes
      associated with disease risk. Therefore, we identified eQTLs in the genetic
      isolate of Norfolk Island (NI) and tested for associations between these and CVD
      risk factors. We measured genome-wide transcript levels of blood lymphocytes in
      330 individuals and used pedigree-based heritability analysis to identify
      heritable transcripts. eQTLs were identified by genome-wide association testing
      of these transcripts. Testing for association between CVD risk factors (i.e.,
      blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712
      heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to
      0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p <
      1.84 * 10(-7)) An eQTL-centric analysis of CVD risk traits revealed multiple
      associations, including 12 previously associated with CVD-related traits. Trait
      versus eQTL regression modeling identified four CVD risk candidates (NAAA,
      PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In
      addition, we implicated several genes previously associated with CVD risk traits,
      including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in
      the NI pedigree and used this to implicate several genes in CVD risk. Future
      studies are required for further assessing the functional importance of these
      eQTLs and whether the findings here also relate to outbred populations. 

PMID- 24314551
TI  - Response to Lee et al.: SNP-based heritability analysis with dense data.

PMID- 24314552
TI  - A review of microfabrication and hydrogel engineering for micro-organs on chips.
AB  - This review highlights recent trends towards the development of in vitro
      multicellular systems with definite architectures, or "organs on chips". First,
      the chemical composition and mechanical properties of the scaffold have to be
      consistent with the anatomical environment in vivo. In this perspective, the
      flourishing interest in hydrogels as cellular substrates has highlighted the main
      parameters directing cell differentiation that need to be recapitulated in
      artificial matrix. Another scaffold requirement is to act as a template to guide
      tissue morphogenesis. Therefore specific microfabrication techniques are required
      to spatially pattern the environment at microscale. 2D patterning is particularly
      efficient for organizing planar polarized cell types such as endothelial cells or
      neurons. However, most organs are characterized by specific sub units organized
      in three dimensions at the cellular level. The reproduction of such 3D patterns
      in vitro is necessary for cells to fully differentiate, assemble and coordinate
      to form a coherent micro-tissue. These physiological microstructures are often
      integrated in microfluidic devices whose controlled environments provide the cell
      culture with more life-like conditions than traditional cell culture methods.
      Such systems have a wide range of applications, for fundamental research, as
      tools to accelerate drug development and testing, and finally, for regenerative
      medicine.

PMID- 24314554
TI  - The potential of anisotropic matrices as substrate for heart valve engineering.
AB  - Cells environment is increasingly recognized as an important function regulator
      through cell-matrix interactions. Extracellular matrix (ECM) anisotropy being a
      key component of heart valves properties, we have devised a method to create
      highly porous anisotropic nanofibrillar scaffolds and studied their suitability
      as cell-support and interactions with human adipose derived stem cells (hADSCs)
      and human valve interstitial cells (hVICs). Anisotropic nanofibrillar scaffolds
      were produced by a modified jet-spraying method that allows the formation of
      aligned nanofibres (600 nm) through air-stream diffraction of a polymer solution
      (poly (epsilon-caprolactone, PCL) and collection onto a variably rotating drum.
      The resulting matrices of high porosity (99%) mimicked valve mechanical
      anisotropy. Dynamically seeded hADSC and hVIC cultured on scaffolds up to 20 days
      revealed that hADSC and hVIC penetration within the matrices was improved by
      anisotropic organization. Within 10 days, cells populated the entire scaffolds
      thickness and produced ECM (collagen I, III and elastin). As a result, mechanical
      properties of the constructs were improved over culture, while remaining
      anisotropic. In contrast to isotropic matrices, anisotropy induced elongated
      hADSCs and hVICs morphology that followed nanofibres orientation. Interestingly,
      these morphological changes did not induce hADSC differentiation towards the
      mesoderm lineages while hVIC recovered a physiological phenotype over culture in
      the biomimetic matrices. Overall, this study indicates that highly porous
      anisotropic jet-sprayed matrices are interesting candidates for valve tissue
      engineering, through anisotropic mechanical properties, efficient cell
      population, conservation of stem cells phenotype and recovery of hVIC
      physiological phenotype.

PMID- 24314553
TI  - Maximizing cartilage formation and integration via a trajectory-based tissue
      engineering approach.
AB  - Given the limitations of current surgical approaches to treat articular cartilage
      injuries, tissue engineering (TE) approaches have been aggressively pursued.
      Despite reproduction of key mechanical attributes of native tissue, the ability
      of TE cartilage constructs to integrate with native tissue must also be optimized
      for clinical success. In this paper, we propose a "trajectory-based" tissue
      engineering (TB-TE) approach, based on the hypothesis that time-dependent
      increases in construct maturation in-vitro prior to implantation (i.e. positive
      rates) may provide a reliable predictor of in-vivo success. As an example TE
      system, we utilized hyaluronic acid hydrogels laden with mesenchymal stem cells.
      We first modeled the maturation of these constructs in-vitro to capture time
      dependent changes. We then performed a sensitivity analysis of the model to
      optimize the timing and amount of data collection. Finally, we showed that
      integration to cartilage in-vitro is not correlated to the maturation state of TE
      constructs, but rather their maturation rate, providing a proof-of-concept for
      the use of TB-TE to enhance treatment outcomes following cartilage injury. This
      new approach challenges the traditional TE paradigm of matching only native state
      parameters of maturity and emphasizes the importance of also establishing an in
      vitro trajectory in constructs in order to improve the chance of in-vivo success.

PMID- 24314555
TI  - Inositol based non-viral vectors for transgene expression in human cervical
      carcinoma and hepatoma cell lines.
AB  - Myo-Inositol (INO) is a biomolecule with crucial functions in many aspects. In
      this study, hyperbranched copolymers for gene delivery were synthesized based on
      inositol and low molecular weight polyethylenimine. The capacity of INO-PEIs to
      load plasmid DNA and their biocompatibility was demonstrated. A tumor target
      ligand, folic acid (FA), which was widely used for drug delivery systems, was
      subsequently conjugated to INO-PEIs and resulted in INO-PEI-FA copolymers. The
      polymers were then evaluated on their activity to mediate transgene expression in
      mammalian cell lines. As indicated, INO-PEIs were able to mediate efficient
      transgene expression, which was particularly noticeable in carcinoma cell line
      HeLa. INO-PEI-FA further improved the efficiency in HepG2. Distribution of INO
      PEI-FA polymers in non-carcinoma NIH 3T3 and carcinoma HeLa cell lines was
      discussed. 

PMID- 24314556
TI  - Tunable diblock copolypeptide hydrogel depots for local delivery of hydrophobic
      molecules in healthy and injured central nervous system.
AB  - Many hydrophobic small molecules are available to regulate gene expression and
      other cellular functions. Locally restricted application of such molecules in the
      central nervous system (CNS) would be desirable in many experimental and
      therapeutic settings, but is limited by a lack of innocuous vehicles able to load
      and easily deliver hydrophobic cargo. Here, we tested the potential for diblock
      copolypeptide hydrogels (DCH) to serve as such vehicles. In vitro tests on
      loading and release were conducted with cholesterol and the anti-cancer agent,
      temozolomide (TMZ). Loading of hydrophobic cargo modified DCH physical properties
      such as stiffness and viscosity, but these could readily be tuned to desired
      ranges by modifying DCH concentration, amino acid composition or chain lengths.
      Different DCH formulations exhibited different loading capacities and different
      rates of release. For example, comparison of different DCH with increasing
      alanine contents showed corresponding increases in both cargo loading capacity
      and time for cargo release. In vivo tests were conducted with tamoxifen, a small
      synthetic hydrophobic molecule widely used to regulate transgene expression.
      Tamoxifen released from DCH depots injected into healthy or injured CNS
      efficiently activated reporter gene expression in a locally restricted manner in
      transgenic mice. These findings demonstrate the facile and predictable tunability
      of DCH to achieve a wide range of loading capacities and release profiles of
      hydrophobic cargos while retaining CNS compatible physical properties. In
      addition, the findings show that DCH depots injected into the CNS can efficiently
      deliver small hydrophobic molecules that regulate gene expression in local cells.

PMID- 24314557
TI  - Anti-mycobacterial activities of synthetic cationic alpha-helical peptides and
      their synergism with rifampicin.
AB  - The rapid emergence of multi-drug resistant tuberculosis (TB) and the lack of
      effective therapies have prompted the development of compounds with novel
      mechanisms of action to tackle this growing public health concern. In this study,
      a series of synthetic cationic alpha-helical antimicrobial peptides (AMPs)
      modified with different hydrophobic amino acids was investigated for their anti
      mycobacterial activity, both alone and in synergistic combinations with the
      frontline anti-tuberculosis drug rifampicin. The addition of thiol groups by
      incorporating cysteine residues in the AMPs did not improve anti-mycobacterial
      activity against drug-susceptible and drug-resistant Mycobacterium tuberculosis,
      while the enhancement of peptide hydrophobicity by adding methionine residues
      increased the efficacy of the primary peptide against all strains tested,
      including clinically isolated multidrug-resistant mycobacteria. The peptide with
      the optimal composition M(LLKK)2M was bactericidal, and eradicated mycobacteria
      via a membrane-lytic mechanism as demonstrated by confocal microscopic studies.
      Mycobacteria did not develop resistance after multiple exposures to sub-lethal
      doses of the peptide. In addition, the peptide displayed synergism with
      rifampicin against both Mycobacterium smegmatis and Mycobacterium bovis BCG and
      additivity against M. tuberculosis. Moreover, such combination therapy is
      effective in delaying the emergence of rifampicin resistance. The ability to
      potentiate anti-TB drug activity, kill drug-resistant bacteria and prevent drug
      resistance highlights the potential utility of the peptide in combating multidrug
      resistant TB.

PMID- 24314558
TI  - Ultra-small BaGdF5-based upconversion nanoparticles as drug carriers and
      multimodal imaging probes.
AB  - A new type of drug-delivery system (DDS) was constructed, in which the anti
      cancer drug doxorubicin (DOX) was conjugated to the ultra-small sized (sub-10 nm)
      BaGdF5:Yb(3+)/Tm(3+) based upconversion nanoparticles (UCNPs). This
      multifunctional DDS simultaneously possesses drug delivery and optical/magnetic/X
      ray computed tomography imaging capabilities. The DOX can be selectively released
      by cleavage of hydrazone bonds in acidic environment, which shows a pH-triggered
      drug release behavior. The MTT assay shows these DOX-conjugated UCNPs exhibit
      obvious cytotoxic effect on HeLa cells. Moreover, to improve the upconversion
      luminescence intensity, core-shell structured UCNPs were constructed. The in
      vitro upconversion luminescence images of these UCNPs uptaken by HeLa cells show
      bright emission with high contrast. In addition, these UCNPs were further
      explored for T1-weighted magnetic resonance (MR) and X-ray computed tomography
      (CT) imaging in vitro. Long-term in vivo toxicity studies indicated that mice
      intravenously injected with 10 mg/kg of UCNPs survived for 40 days without any
      apparent adverse effects to their health. The results indicate that this
      multifunctional drug-delivery system with optimized size, excellent optical/MR/CT
      trimodal imaging capabilities, and pH-triggered drug release property is expected
      to be a promising platform for simultaneous cancer therapy and bioimaging.

PMID- 24314559
TI  - Surgical treatment of synovial chondromatosis of the temporomandibular joint with
      erosion of the skull base: a case report and review of the literature.
AB  - Synovial chondromatosis (SC) is a rare metaplastic disease of the larger joints.
      It is rarely observed in smaller joints, especially in the temporomandibular
      joint (TMJ). This disease is considered to be metaplastic and shows no malignant
      tendencies, but can become locally aggressive, erode the cranial base, and even
      spread intracranially. To date, nine cases of spread into the intracranial space
      have been reported in the literature; however, the disease remained extradural in
      all cases. The authors present a review of the literature and report the case of
      a 70-year-old man with SC of the right TMJ that had eroded the cranial base,
      reaching the dura mater; a large intracranial mass was not present. The disease
      was considered to be stage 3 according to Milgram's classification. The patient
      was treated surgically, the tumour mass was removed, reconstruction of the
      cranial base was performed using titanium mesh, and the joint was reconstructed
      with a temporal muscle interposition flap. Diagnostic images and intraoperative
      photographs are also presented.

PMID- 24314560
TI  - [The fibroid as clinical problem].
AB  - Uterine fibroids are the most common benign tumours that affect women of
      reproductive age and they represent the main indication for surgery for benign
      uterine pathology. In 25% of cases, they become clinically apparent, causing
      heavy menstrual bleeding, pelvic pain and/or infertility. Therefore, fibroids
      have a notable impact on the economic costs for the health system and also on the
      quality of life of the women they afflict. Although MRI is the most precise
      technique to diagnose fibroids, ultrasound remains the most cost-effective
      method. Surgery has been the treatment of choice for years, and several minimally
      invasive procedures have recently been developed. There are a wide variety of
      conservative medical treatment options, which are continually expanding. Research
      on the biology of these tumours can lead to new therapeutic options for the
      management of fibroids as we better understand the role that growth factors and
      genetic mutations play in them. 

PMID- 24314561
TI  - [Current role of conservative surgery].
AB  - It is not easy to establish the true impact of fibroids on fertility.
      Fibroidectomy in sterile patients with subserosal fibroids does not offer the
      best results for patients with in situ fibroids. Women with intramural fibroids
      appear to present reduced fertility and increased miscarriage rates, compared
      with women without fibroids. However, fibroidectomy does not always reverse this
      effect (does not increase the clinical pregnancy or "take-home baby" rates), but
      the quality of the studies is still poor. Fibroids with a submucosal component
      significantly decrease implantation and pregnancy rates with regard to sterile
      controls. Fibroid exeresis clearly improves fertility results. There is a need
      for better quality studies aimed at assessing the impact of intramural fibroids,
      with a special focus on factors such as size, number and proximity to the
      endometrium. The majority of cases can be treated endoscopically. This procedure
      needs properly trained teams who monitor their results and who are able to offer
      the same guarantees that laparotomy affords, both in terms of the surgical
      technique and the patients' obstetric future. Laparoscopic fibroidectomy offers
      results comparable to laparotomy and minimizes the formation of adhesions, blood
      loss, hospital stay and the time to return to work. For sterile patients,
      laparoscopic fibroidectomy may be the first choice therapy. 

PMID- 24314562
TI  - [Hysterectomy for fibroids].
AB  - Occasionally, the indicated treatment for cases of fibroid uterus is a
      hysterectomy. Surgical approaches for hysterectomy include abdominal, vaginal or
      laparoscopic. The determinant for selecting the surgical approach is uterine
      weight. In this article, we conducted a review of studies that compared the
      various surgical techniques for hysterectomy, as well as the steps to consider
      when performing a laparoscopic hysterectomy in large uteri. 

PMID- 24314563
TI  - [Non-surgical approach for symptomatic fibroids. Physical methods: selective
      embolization].
AB  - The approach to symptomatic uterine fibroids has seen a marked evolution in
      recent years thanks to the emergence of minimally invasive techniques that allow
      for uterine preservation. Selective uterine artery embolization (UAE) consists of
      the complete occlusion of the 2 uterine arteries with embolic particles in order
      to produce ischemic necrosis of the fibroids without permanently affecting the
      normal uterine tissue. This technique significantly reduces the amount of
      bleeding and causes a reduction in uterine volume at 3 months postprocedure,
      which is maintained over time, allowing for 70% of patients to avoid surgery.
      Moreover, UAE entails shorter surgical times, reduced hospital stays and fewer
      days needed to return to work when compared with traditional surgical techniques
      (hysterectomy and fibroidectomy), without any differences in the quality-of-life
      scales at 5 years. UAE should therefore be included in the therapeutic options
      offered to patients with symptomatic fibroid uteri. 

PMID- 24314564
TI  - [Treatment of uterine fibroids using high-intensity ultrasound].
AB  - High-intensity ultrasound surgery is being actively introduced as an alternative
      treatment to conventional surgery for uterine fibroids. Numerous studies have
      shown that high-intensity ultrasound surgery is a safe and effective treatment,
      with fewer side effects than fibroidectomy and hysterectomy, and is cost
      effective. It is now possible to offer this alternative therapy to patients with
      symptomatic uterine fibroids. We describe the technical basis of ultrasound
      surgery, the pretherapy selection of patients, the limiting factors and the risks
      of high-intensity ultrasound therapy. We describe our unit's clinical experience
      with 319 patients treated in an outpatient regimen, which resulted in a high rate
      of success (81%) and an acceptable rate of mild complications, as well as a
      virtually immediate return to daily activities. We comment on the follow-up of
      pregnancies that occurred after treatment with high-intensity focused ultrasound
      (HIFU) with no side effects attributable to the therapy. 

PMID- 24314565
TI  - [Hormonal treatments for hemorrhaging secondary to fibroids. An alternative or
      complement to surgery?].
AB  - The main objective of treatment in women with uterine fibroids is the control of
      associated symptoms such as abnormal uterine bleeding, pain and pressure.
      Although the cost and potential adverse effects of the long-term use of medical
      treatment may limit its use for a long time, this alternative should be
      considered before indicating surgical treatment. At present, we have a
      considerable variety of drugs that, although not specific treatments for
      fibroids, may be used for the short to medium-term management of bleeding;
      however, we have still not found an alternative that eliminates the need for
      invasive treatments. Further research in this field is therefore warranted. Given
      the heterogeneity of fibroids and the lack of effective treatments in controlling
      their growth, the identification of signals that stimulate the onset and growth
      of these fibroids opens doors to the development of new therapies. In the future
      we may be able to differentiate classes of fibroids by molecular techniques and
      thereby implement specific treatments that control their development and their
      associated symptoms. 

PMID- 24314567
TI  - [Ulipristal acetate, 5mg: a new alternative].
AB  - Fibroids have a high prevalence (approaching 50%) in the female population.
      Although they are a benign entity, they represent a health problem of
      considerable magnitude, causing hemorrhaging, pain and sterility. Surgical
      treatment is currently safe and effective, but in recent decades numerous less
      invasive alternatives have appeared, such as uterine artery embolization and
      thermal ablation (HIFU and radiofrequency). New possibilities for medical
      treatment have also emerged, such as GnRh analogues, aromatase inhibitors and
      selective progesterone receptor modulators (SPRMs). SPRMs act through
      progesterone receptors and behave as agonists or antagonists in various target
      organs. Among them, ulipristal acetate (UA) inhibits the proliferation and
      induction of apoptosis and cell death pathways in leiomyoma cells, translating at
      the clinical level to smaller fibroids and lower uterine volumes, with no
      significant side effects. UA also produces amenorrhea in most patients.
      Randomized, phase III (PEARL I and II) clinical trials have shown the efficacy
      and security of UA versus placebo and leuprolide acetate (LA). UA is similar to
      LA, and superior to placebo in controlling bleeding and decreasing the size of
      the fibroid, with fewer side effects than LA. The safety and tolerance of UA have
      been satisfactory. UA is a reality in the preoperative treatment of fibroids,
      with broad potential for further development. 

PMID- 24314566
TI  - [GnRH analogues for the treatment of fibroids].
AB  - Uterine fibroids are benign tumors that are very common in women and may present
      significant symptoms in 20%-50% of cases. When they require action, their
      traditional management has been surgery (hysterectomy or fibroidectomy); however
      medical alternatives have been proposed, given that surgery is associated with a
      certain morbidity and mortality and involves healthcare costs. Within the
      pharmacological management of uterine fibroids, GnRH analogues are the best known
      and most commonly used drugs, although their indications are limited by the side
      effects associated with long-term treatment. Their primary indication is based on
      preoperative treatment (to hysterectomy or fibroidectomy) and in selected cases
      of patients close to menopause or who want more conservative management. These
      analogues are able to significantly reduce the uterine volume, the size of the
      fibroid and their accompanying symptoms. Their main disadvantage, however, lies
      in the reversibility of their effect when treatment is discontinued, along with
      the side effects associated with hypoestrogenism, such as climacteric symptoms
      and loss of bone mass. "Add-back" therapies, which associate low-dose estrogens
      to aGnRH, allow for extended use thanks to decreased side effects without
      affecting the benefits.

PMID- 24314568
TI  - [Anemia as a surgical risk factor].
AB  - Perioperative anemia is common in patients undergoing surgery and is associated
      with increased morbidity and mortality and a decreased quality of life. The main
      causes of anemia in the perioperative context are iron deficiency and chronic
      inflammation. Anemia can be aggravated by blood loss during surgery, and is most
      commonly treated with allogeneic transfusion. Moreover, blood transfusions are
      not without risks, once again increasing patient morbidity and mortality. Given
      these concerns, we propose to review the pathophysiology of anemia in the
      surgical environment, as well as its treatment through the consumption of iron
      rich foods and by oral or intravenous iron therapy (iron sucrose and iron
      carboxymaltose). In chronic inflammatory anemia, we use erythropoiesis
      stimulating agents (erythropoietin alpha) and, in cases of mixed anemia, the
      combination of both treatments. The objective is always to reduce the need for
      perioperative transfusions and speed the recovery from postoperative anemia, as
      well as decrease the patient morbidity and mortality rate. 

PMID- 24314569
TI  - [Management of fibroids].
AB  - Approximately 25% of reproductive age females have fibroids; of these 50% have
      relevant symptoms. Abnormal menstrual bleeding, pain, pressure, infertility and
      repeated miscarriages are frequently associated with fibroids. Although surgery
      and radiological therapies are frequently used to manage these tumors, medical
      therapies are considered the first-line treatment for fibroids. The objective of
      this article is to serve as a guide for decision-making in the management of
      fibroids. 

PMID- 24314570
TI  - Preserving soft tissue after placing implants in fresh extraction sockets in the
      maxillary esthetic zone and a prosthetic template for interim crown fabrication:
      a prospective study.
AB  - STATEMENT OF PROBLEM: The technique of immediate implant placement is said to
      have success rates similar to those of implantation into a healed socket. An
      implant-supported restoration in an esthetic area must achieve a harmonious
      balance of functional, esthetic, and biologic imperatives to be considered
      effective. PURPOSE: The purpose of this clinical study was to assess the height
      of the interproximal gingival papillae adjacent to immediate implants with
      immediate loading. The hypothesis was that specific positioning of the proximal
      contact areas of the interim crowns would facilitate the maintenance or
      regeneration of the interproximal papilla. MATERIAL AND METHODS: Twenty-eight
      participants were provided implants (n=36) in the anterior maxillary area that
      were loaded with a specifically contoured interim crown immediately after tooth
      extraction. The proximal contact areas of the interim crowns were positioned 5 to
      6 mm incisal to the interproximal bony crest by using a prosthetic template.
      Papilla height was classified according to a previously described papilla index.
      A comparison was made between the papilla height before the extraction, at
      interim crown placement after the implant placement, and at 6 and 12 months
      postoperatively. Parametric and nonparametric tests were used when appropriate
      (Kolmogorov-Smirnov). Significance was expressed at the alpha=.05 level. Cross
      tables were used to describe the changes in the papilla index score. RESULTS:
      During the 1-year follow-up, the score of the distal and mesial papilla indices
      increased significantly (repeated-measures Friedman exact test; P=.035 and
      P=.002). CONCLUSIONS: This prospective study indicated that the use of a
      prosthetic template for positioning an interim crown on immediately placed
      implants and for ensuring that the proximal contact areas of the crown with
      adjacent teeth are 5 to 6 mm incisal to the interproximal bony crest does not
      seem to hinder the maintenance or regeneration of the height of the interproximal
      papillae.

PMID- 24314571
TI  - Finite element analysis of three zygomatic implant techniques for the severely
      atrophic edentulous maxilla.
AB  - STATEMENT OF PROBLEM: A variety of zygomatic implantation techniques currently
      exist; however, a consensus regarding the most suitable method has not yet been
      reached. PURPOSE: The purpose of this study was to evaluate and compare 3
      zygomatic implantation techniques and to clarify the optimal number and position
      of zygomatic and dental implants for the reconstruction of the severely atrophied
      edentulous maxilla. MATERIAL AND METHODS: A 3-dimensional finite element analysis
      craniofacial model was constructed from the computed tomography data of a
      selected patient with a severely atrophic edentulous maxilla. Modeled zygomatic
      implants were inserted into the craniofacial model with 3 surgical techniques
      (classic Branemark, exteriorized, and extramaxillary), and with 3 model
      variations that involved the number and position of zygomatic and dental
      implants. The zygomatic implants were loaded with a vertical force of 150 N and a
      lateral force of 50 N. The stresses on and deformations of the bones and implants
      were then observed and compared. RESULTS: No obvious differences in the amount
      and distribution of stress on the external craniofacial bones were detected in
      the models. The lowest stresses on the zygomatic implants were observed in the
      exteriorized technique group. The lowest deformations of the bone that surrounds
      zygomatic implants and dental implants were observed in the exteriorized
      technique and classic Branemark technique groups. For the exteriorized technique
      group, the model with 1 dental implant in the site of the maxillary lateral
      incisor exhibited the lowest stress on the zygomatic implants and the least
      deformation of the bone surrounding the zygomatic and dental implants.
      CONCLUSIONS: All 3 zygomatic implant techniques resulted in more or less
      homogeneous transference of force and thus could reconstruct the edentulous
      maxilla; however, the exteriorized technique with 1 dental implant in the lateral
      incisor appeared to be the most appropriate reconstruction method for the
      severely atrophied edentulous maxilla.

PMID- 24314572
TI  - Water aerosol protective device used during tooth preparation for patients with a
      maxillectomy.

PMID- 24314577
TI  - Searching for Trichinella: not all pigs are created equal.
AB  - Each year, millions of pigs worldwide are tested for Trichinella spp. at
      slaughterhouses with negative results. Yet, thousands of people acquire
      trichinellosis by consuming pork. So, where is the problem? Testing for
      Trichinella spp. is often performed on the 'wrong' animals; while the parasites
      are mainly circulating in backyard and free-ranging pigs, herds kept under
      controlled management conditions are the ones tested. Veterinary services should:
      (i) introduce a risk-based surveillance system for Trichinella by documenting the
      control of housing conditions and feedstuff sources, and (ii) introduce a
      capillary network of field laboratories for monitoring the parasites in free
      ranging and backyard pigs. Investment of funds into the education of farmers,
      hunters, and consumers should be a priority for public health services. 

PMID- 24314579
TI  - Quantum shifts in radiology: the impending death of the radiograph?

PMID- 24314578
TI  - The global burden of foodborne parasitic diseases: an update.
AB  - Foodborne diseases (FBDs) are a major cause of morbidity and mortality in the
      human population. Accurate information on the burden of FBDs is needed to inform
      policy makers and allocate appropriate resources for food safety control and
      intervention. Consequently, in 2006 the WHO launched an initiative to estimate
      the global burden of FBDs in terms of Disability Adjusted Life Years (DALYs).
      This review gives an update of the progress on evaluating the burden of foodborne
      parasitic diseases that has been generated by this study. Results to date
      indicate that parasitic diseases that can be transmitted through food make a
      substantial contribution to the global burden of disease. 

PMID- 24314580
TI  - Improving management of osteoporosis through simple changes in reporting
      fragility fractures.

PMID- 24314581
TI  - Canadian Association of Radiologists Technical Standards for Bone Mineral
      Densitometry Reporting.

PMID- 24314582
TI  - The emergence of ultra-low--dose computed tomography and the impending
      obsolescence of the plain radiograph?

PMID- 24314583
TI  - Radiation dose reduction in computed tomography: implementation of an iterative
      image reconstruction method.

PMID- 24314584
TI  - Muscle-specific kinase antibody associated myasthenia gravis after bone marrow
      transplantation.
AB  - Myasthenia gravis is a rare complication of bone marrow transplantation and graft
      versus host disease. We report a 30-year-old woman presented with oculobulbar and
      proximal limb weakness after allogeneic bone marrow transplantation for chronic
      myelogenous leukemia. Also, she developed graft versus host disease following
      bone marrow transplantation. Investigations led to the diagnosis of muscle
      specific kinase antibody related myasthenia gravis. There have been only two case
      reports of muscle specific kinase antibody positive myasthenia gravis after bone
      marrow transplantation in the literature, but none of the previously reported
      cases had graft versus host disease. 

PMID- 24314585
TI  - Inflammatory myopathy with abundant macrophages (IMAM): the immunology revisited.
AB  - We describe a patient with a clinically atypical presentation of inflammatory
      myopathy with abundant macrophages (IMAM) but with convincing muscle biopsy
      features of this subform of inflammatory myopathy. IMAM is characterized mainly
      by a conspicuous infiltration of muscle and connective tissue by numerous
      macrophages remote from necrotic and basophilic regenerating muscle fibers.
      Typically few, mostly CD4(+) T helper (Th) cells are also present. Here, we
      report a patient with IMAM and demonstrate, that most macrophages express the
      macrophage mannose receptor 1 (CD206) corresponding to alternatively activated
      (M2) polarization. Accordingly, signal transducer and activator of transcription
      6 (STAT6), involved in Th2-M2 immunity, was expressed at high levels in skeletal
      muscle. However, TNFalpha, IFNgamma and STAT1, mediators of the T helper 1
      classically activated (M1) response were elevated in skeletal muscle and in
      blood, while expression of CD206 was elevated in skeletal muscle only. Our
      results argue that IMAM could be a distinct entity between the inflammatory
      myopathies rather than a subform of dermatomyositis. 

PMID- 24314586
TI  - The influence of fish-oil lipid emulsions on retinopathy of prematurity in very
      low birth weight infants: a randomized controlled trial.
AB  - OBJECTIVE: To compare the effect of two lipid emulsions on the development of
      retinopathy of prematurity in very low birth weight infants. DESIGN: Randomized
      controlled study. PATIENTS AND METHODS: Eighty very low birth weight infants
      receiving parenteral nutrition from the first day of life were evaluated. One of
      the two lipid emulsions were used in the study infants: Group 1 (n=40) received
      fish-oil based lipid emulsion (SmofLipid(r)) and Group 2 (n=40) soybean oil based
      lipid emulsion (Intralipid(r)). MAIN OUTCOME MEASURES: The development of
      retinopathy of prematurity and the need for laser photocoagulation were assessed.
      RESULTS: The maternal and perinatal characteristics were similar in both groups.
      The median (range) duration of parenteral nutrition [14days (10-28) vs 14 (10
      21)] and hospitalization [34days (20-64) vs 34 (21-53)] did not differ between
      the groups. Laboratory data including complete blood count, triglyceride level,
      liver and kidney function tests recorded before and after parenteral nutrition
      also did not differ between the two groups. In Group 1, two patients (5.0%) and
      in Group 2, 13 patients (32.5%) were diagnosed with retinopathy of prematurity
      (OR: 9.1, 95% CI 1.9-43.8, p=0.004). One patient in each group needed laser
      photocoagulation, without significant difference. Multivariate analysis showed
      that only receiving fish-oil emulsion in parenteral nutrition decreased the risk
      of development of retinopathy of prematurity [OR: 0.76, 95% CI (0.06-0.911),
      p=0.04]. CONCLUSIONS: Premature infants with very low birth weight receiving an
      intravenous fat emulsion containing fish oil developed less retinopathy of
      prematurity.

PMID- 24314587
TI  - Reply to the letter to the editor "are leptin levels a cause or an indicator of
      cardiovascular risk?".

PMID- 24314588
TI  - Proteins related to the spindle and checkpoint mitotic emphasize the different
      pathogenesis of hypoplastic MDS.
AB  - Some studies show that alterations in expression of proteins related to mitotic
      spindle (AURORAS KINASE A and B) and mitotic checkpoint (CDC20 and MAD2L1) are
      involved in chromosomal instability and tumor progression in various solid and
      hematologic malignancies. This study aimed to evaluate these genes in MDS
      patients. The cytogenetics analysis was carried out by G-banding, AURKA and AURKB
      amplification was performed using FISH, and AURKA, AURKB, CDC20 and MAD2L1 gene
      expression was performed by qRT-PCR in 61 samples of bone marrow from MDS
      patients. AURKA gene amplification was observed in 10% of the cases, which also
      showed higher expression levels than the control group (p=0.038). Patients with
      normo/hypercellular BM presented significantly higher expression levels than
      hypocellular BM patients, but normo and hypercellular BM groups did not differ.
      After logistic regression analysis, our results showed that HIGH expression
      levels were associated with increased risk of developing normo/hypercellular MDS.
      It also indicated that age is associated with AURKA, CDC20 and MAD2L1 HIGH
      expression levels. The distinct expression of hypocellular patients emphasizes
      the prognostic importance of cellularity to MDS. The amplification/high
      expression of AURKA suggests that the increased expression of this gene may be
      related to the pathogenesis of disease. 

PMID- 24314590
TI  - Comparison of 24-month outcomes in chelated and non-chelated lower-risk patients
      with myelodysplastic syndromes in a prospective registry.
AB  - This 5-year, prospective registry enrolled 600 lower-risk MDS patients (pts) with
      transfusional iron overload. Clinical outcomes were compared between chelated and
      nonchelated pts. At baseline, cardiovascular comorbidities were more common in
      non-chelated pts, and MDS therapy was more common in chelated pts. At 24 months,
      chelation was associated with longer median overall survival (52.2 months vs.
      104.4 months; p<.0001) and a trend toward longer leukemia-free survival and fewer
      cardiac events. No differences in safety were apparent between groups.
      Limitations of this analysis included, varying time from diagnosis and duration
      of chelation, and the fact that the decision to chelate may have been influenced
      by pt clinical status. 

PMID- 24314589
TI  - Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with
      chronic lymphocytic leukemia (CLL) and an adverse biologic profile.
AB  - In 45, <= 60 years old patients with CLL and an adverse biologic profile, a front
      line treatment with Fludarabine and Campath (Alemtuzumab((r))) was given. The
      overall response rate was 75.5%, the complete response rate (CR) 24.4% with the
      lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year
      progression-free survival (PFS) and overall survival were 42.5% and 79.9%,
      respectively. PFS was significantly influenced by CLL duration, beta2
      microglobulin, and improved by post-remissional stem cell transplantation. Front
      line fludarabine and alemtuzumab showed a manageable safety profile and evidence
      of a benefit in a small series of CLL patients with adverse biologic features.

PMID- 24314591
TI  - Use of serotonergic antidepressants and bleeding risk in patients undergoing
      surgery.
AB  - BACKGROUND: Serotonergic antidepressants (SADs) are associated with increased
      bleeding risk. OBJECTIVES: To develop optimal guidelines for the usage of
      antidepressants in the perioperative period, this review of the bleeding risk
      associated with SADs was conducted. METHODS: A total of 10 original articles
      describing the relationship between SAD use and perioperative bleeding published
      in English before June 2013 were selected and reviewed. RESULTS: A total of 6
      studies showed positive associations between SAD use and perioperative bleeding.
      In particular, SAD use before orthopedic or breast surgery was associated with a
      tendency toward increased intraoperative or postoperative bleeding (i.e.,
      increased need for transfusion during surgery, greater amount of intraoperative
      blood loss, bleeding events requiring intervention, or reoperation owing to
      postoperative bleeding). However, 3 studies among SAD users undergoing coronary
      artery bypass grafting and 1 study in SAD users undergoing facial surgery did not
      report an increased risk for postoperative bleeding. CONCLUSIONS: The risks and
      benefits of SAD use should be weighed in all patients undergoing surgical
      operations. Physicians may consider planned discontinuation of SADs 2 weeks
      before the operation in patients with a high risk of bleeding but in the stable
      phase of depression. SAD discontinuation syndrome should be managed
      appropriately. If, despite the expected exacerbation of depression after
      discontinuation of antidepressants, discontinuation of SADs is nonetheless
      required because of the patient's clinical risk of bleeding, changing to an
      antidepressant that does not, or less potently, inhibits serotonin reuptake
      (e.g., bupropion or mirtazapine) can be considered.

PMID- 24314592
TI  - Ectopia lentis, "the sign of the tremulous iris," and hypovitaminosis C: a
      classic eye finding with a neuropsychiatric twist.

PMID- 24314593
TI  - Nurse screening for delirium in older patients attending the emergency
      department.
AB  - BACKGROUND: Delirium in older emergency department (ED) patients is common,
      associated with many adverse outcomes, and costly to manage. Delirium detection
      in the ED is almost universally poor. OBJECTIVES: The authors aimed to develop a
      simple clinical risk screening tool that could be used by ED nurses as part of
      their initial assessment to identify patients at risk of delirium. METHODS: A
      prospective cross-sectional study of patients 65 years and older attending a
      single ED. RESULTS: Of 320 enrolled patients, 23 (7.2%) had delirium. Logistic
      regression analysis revealed 3 risk factors strongly associated with delirium
      risk: cognitive impairment, depression, and an abnormal heart rate/rhythm.
      Weighting these variables based on the strength of their association with
      delirium yielded a risk score from 0-4 inclusive. A cutoff of 2 or more in that
      score would have given a sensitivity of 87%, specificity of 70%, and NPV of 99%,
      while avoiding further diagnostic workup for delirium in approximately two-thirds
      of all patients, when used as an initial screen. CONCLUSIONS: A simple risk
      screening tool using factors evident on initial nurse assessment can be used to
      identify patients at risk of delirium. Further trials are needed to test whether
      the tool improves patient outcomes.

PMID- 24314594
TI  - Factitious mastectomy and hysterectomy: the importance of staying abreast of the
      medical record.

PMID- 24314595
TI  - Number variant analysis in a hospitalized patient with psychosis.

PMID- 24314596
TI  - Outcome prediction of initial lamotrigine monotherapy in adult patients with
      newly diagnosed localization related epilepsies.
AB  - OBJECTIVE: To develop and test model to predict outcome of treatment with initial
      lamotrigine monotherapy in adult patients with newly diagnosed localization -
      related epilepsy, using data available at the time of diagnosis. METHODS:
      Prospective longitudinal study included consecutive series of adult patients with
      newly diagnosed localization - related epilepsy started of lamotrigine
      monotherapy. Logistic regression analysis using backward procedure was performed
      with treatment failure as the outcome variable. We evaluated both calibration and
      discrimination of the model. Internal validation of the model was performed with
      bootstrapping techniques. RESULTS: A total of 159 patients on lamotrigine
      monotherapy have been included in final analysis. Among them 78 (49.06%) patients
      had persistent seizures. Finally fitted multivariate model included: 1) age at
      therapy start, 2) presence of complex partial seizures, 3) aetiology of epilepsy
      and 4) interaction of age and epilepsy aetiology. Estimated odds ratio for
      seizure relapse in old patients with symptomatic epilepsy is lower than for the
      old patients with cryptogenic epilepsy, despite strong positive covariate effect
      of epilepsy aetiology. The model correctly classified 69.23% patients with
      seizure relapses and 81.48% of patients with seizure freedom, with estimated c -
      statistic of 0.80. Testing practical application we observed threefold increase
      or reduction of odds for the seizure relapse after model's positive or negative
      prediction respectively. CONCLUSION: Standard clinical data were modesty adequate
      to predict response to the initial trial of lamotrigine in adult patients with
      localization related epilepsy. Better markers of antiepileptic failure are
      required to guide optimal patient counselling and clinical decisions. Formal
      interaction analysis of variables improves outcome prediction and may be a key to
      correct interpretation of data.

PMID- 24314597
TI  - Interpenetrating networks based on gelatin methacrylamide and PEG formed using
      concurrent thiol click chemistries for hydrogel tissue engineering scaffolds.
AB  - The integration of biological extracellular matrix (ECM) components and synthetic
      materials is a promising pathway to fabricate the next generation of hydrogel
      based tissue scaffolds that more accurately emulate the microscale heterogeneity
      of natural ECM. We report the development of a bio/synthetic interpenetrating
      network (BioSINx), containing gelatin methacrylamide (GelMA) polymerized within a
      poly(ethylene glycol) (PEG) framework to form a mechanically robust network
      capable of supporting both internal cell encapsulation and surface cell
      adherence. The covalently crosslinked PEG network was formed by thiol-yne
      coupling, while the bioactive GelMA was integrated using a concurrent thiol-ene
      coupling reaction. The physical properties (i.e. swelling, modulus) of BioSINx
      were compared to both PEG networks with physically-incorporated gelatin (BioSINP)
      and homogenous hydrogels. BioSINx displayed superior physical properties and
      significantly lower gelatin dissolution. These benefits led to enhanced
      cytocompatibility for both cell adhesion and encapsulation; furthermore, the
      increased physical strength provided for the generation of a micro-engineered
      tissue scaffold. Endothelial cells showed extensive cytoplasmic spreading and the
      formation of cellular adhesion sites when cultured onto BioSINx; moreover, both
      encapsulated and adherent cells showed sustained viability and proliferation. 

PMID- 24314598
TI  - Impact of and interaction between the availability of prior examinations and DBT
      on the interpretation of negative and benign mammograms.
AB  - RATIONALE AND OBJECTIVES: To assess the interaction between the availability of
      prior examinations and digital breast tomosynthesis (DBT) in decisions to recall
      a woman during interpretation of mammograms. MATERIALS AND METHODS: Eight
      radiologists independently interpreted twice 36 mammography examinations, each of
      which had current and prior full-field digital mammography images (FFDM) and DBT
      under a Health Insurance Portability and Accountability Act-compliant,
      institutional review board-approved protocol (written consent waived). During the
      first reading, three sequential ratings were provided using FFDM only, followed
      by FFDM + DBT, and then followed by FFDM + DBT + priors. The second reading
      included FFDM only, then FFDM + priors, and then FFDM + priors + DBT. Twenty-two
      benign cases clinically recalled, 12 negative/benign examinations (not recalled),
      and two verified cancer cases were included. Recall recommendations and
      interaction between the effect of priors and DBT on decisions were assessed (P =
      .05 significance level) using generalized linear model (PROC GLIMMIX, SAS,
      version 9.3; SAS Institute, Cary, NC) accounting for case and reader variability.
      RESULTS: Average recall rates in noncancer cases were significantly reduced (51%;
      P < .001) with the addition of DBT and with addition of priors (23%; P = .01). In
      absolute terms, the addition of DBT to FFDM reduced the recall rates from 0.67 to
      0.42 and from 0.54 to 0.27 when DBT was available before and after priors,
      respectively. Recall reductions were from 0.64 to 0.54 and from 0.42 to 0.33 when
      priors were available before and after DBT, respectively. Regardless of the
      sequence in presentation, there were no statistically significant interactions
      between the effect of availability of DBT and priors (P = .80). CONCLUSIONS:
      Availability of both priors and DBT are independent primary factors in reducing
      recall recommendations during mammographic interpretations.

PMID- 24314599
TI  - Hiatal herniation of the stomach and pancreas in a patient with oxygen
      desaturations.

PMID- 24314600
TI  - Methods to determine resistance to anthelmintics when continuing larval
      development occurs.
AB  - The in vivo faecal egg count reduction test (FECRT) is the most commonly used
      test to detect anthelmintic resistance (AR) in gastrointestinal nematodes (GIN)
      of ruminants in pasture based systems. However, there are several variations on
      the method, some more appropriate than others in specific circumstances. While in
      some cases labour and time can be saved by just collecting post-drench faecal
      worm egg counts (FEC) of treatment groups with controls, or pre- and post-drench
      FEC of a treatment group with no controls, there are circumstances when pre- and
      post-drench FEC of an untreated control group as well as from the treatment
      groups are necessary. Computer simulation techniques were used to determine the
      most appropriate of several methods for calculating AR when there is continuing
      larval development during the testing period, as often occurs when anthelmintic
      treatments against genera of GIN with high biotic potential or high re-infection
      rates, such as Haemonchus contortus of sheep and Cooperia punctata of cattle, are
      less than 100% efficacious. Three field FECRT experimental designs were
      investigated: (I) post-drench FEC of treatment and controls groups, (II) pre- and
      post-drench FEC of a treatment group only and (III) pre- and post-drench FEC of
      treatment and control groups. To investigate the performance of methods of
      indicating AR for each of these designs, simulated animal FEC were generated from
      negative binominal distributions with subsequent sampling from the binomial
      distributions to account for drench effect, with varying parameters for worm
      burden, larval development and drench resistance. Calculations of percent
      reductions and confidence limits were based on those of the Standing Committee
      for Agriculture (SCA) guidelines. For the two field methods with pre-drench FEC,
      confidence limits were also determined from cumulative inverse Beta distributions
      of FEC, for eggs per gram (epg) and the number of eggs counted at detection
      levels of 50 and 25. Two rules for determining AR: (1) %reduction (%R)<95% and
      lower confidence limit <90%; and (2) upper confidence limit <95%, were also
      assessed. For each combination of worm burden, larval development and drench
      resistance parameters, 1000 simulations were run to determine the number of times
      the theoretical percent reduction fell within the estimated confidence limits and
      the number of times resistance would have been declared. When continuing larval
      development occurs during the testing period of the FECRT, the simulations showed
      AR should be calculated from pre- and post-drench worm egg counts of an untreated
      control group as well as from the treatment group. If the widely used resistance
      rule 1 is used to assess resistance, rule 2 should also be applied, especially
      when %R is in the range 90 to 95% and resistance is suspected.

PMID- 24314601
TI  - Enzymatic hydrolysis of pretreated waste paper--source of raw material for
      production of liquid biofuels.
AB  - Enzymatic hydrolysis of waste paper is becoming a perspective way to obtain raw
      material for production of liquid biofuels. Reducing sugars solutions that arise
      from the process of saccharification are a precursors for following or
      simultaneous fermentation to ethanol. Different types of waste paper were
      evaluated, in terms of composition and usability, in order to select the
      appropriate type of the waste paper for the enzymatic hydrolysis process.
      Novozymes(r) enzymes NS50013 and NS50010 were used in a laboratory scale trials.
      Technological conditions, which seem to be the most suitable for hydrolysis after
      testing on cellulose pulp and filter paper, were applied to hydrolysis of widely
      available waste papers - offset paper, cardboard, recycled paper in two
      qualities, matte MYsol offset paper and for comparison again on model materials.
      The highest yields were achieved for the cardboard, which was further tested
      using various pretreatment combinations in purpose of increasing the hydrolysis
      yields. 

PMID- 24314602
TI  - Electrode as sole electrons donor for enhancing decolorization of azo dye by an
      isolated Pseudomonas sp. WYZ-2.
AB  - Pseudomonas sp. WYZ-2 was isolated from a biocathode which accelerating azo dye
      decolorization. When the electrode was polarized at -0.8 V (vs. SCE), WYZ-2 could
      exist on electrode, because the current of working electrode stabilized at -0.35
      mA from -0.13 mA after inoculation. Moreover, cyclic voltammetry scanned an
      unidentified redox-active molecule which involved in the electron charge transfer
      potentially. On azo dye decolorization experiments by WYZ-2 modified electrode,
      electrochemical tests also indicated that the catalytic ability of WYZ-2 modified
      electrode was improved because charge transfer resistance decreased to 255 Omega
      from 720 Omega, azo dye reduction potential was shifted to -0.78 V from -0.89 V,
      and the maximum decolorization efficiency of azo dye was increased to 93.4% from
      53.2%, comparing with unmodified electrode. Although numerous studies on azo dye
      decolorization employed biological agents, electrochemical activity bacteria
      accelerate the decolorization process using electrode as sole electron source has
      seldom been reported.

PMID- 24314604
TI  - Clinical characteristics and metabolic abnormalities in preschool-age children
      with urolithiasis in southeast Anatolia.
AB  - OBJECTIVE: Data on urolithiasis in preschool-age children are limited. The aim of
      this study was to investigate the metabolic etiology and clinical findings of
      preschool-age children with urolithiasis. METHODS: The medical records of 143
      preschool-age children (81 boys, 62 girls, aged 2-6 years) with urolithiasis were
      retrospectively analyzed. Results of physical examination, serum biochemistry,
      and urine metabolic evaluation (including urinary citrate, oxalate, calcium, uric
      acid, cystine, and magnesium) were recorded. RESULTS: The mean age at diagnosis
      was 3.7 +/- 1.3 years. A family history of stone disease was found in 79.7% of
      patients, and 37% of parents had consanguineous marriages. The most common
      presenting symptoms were hematuria (33%) and urinary tract infection (UTI; 29%).
      Metabolic abnormalities were found in 119 (83.2%) patients, including
      hyperuricosuria in 24.5%, hypocitraturia in 23.8%, hyperoxaluria in 21.7%,
      hypercalciuria in 21.0%, cystinuria in 7.7%, and hypomagnesuria in 1.4%. Multiple
      metabolic abnormalities were found in 24 (16.8%) patients. Results of 28 stone
      analyses revealed calcium oxalate or phosphate, cystine, and uric acid in 15,
      nine, and four of the patients, respectively. (99m)Technetium-dimercaptosuccinic
      acid renal scintigraphy revealed that 27.8% of the children with UTI had renal
      parenchymal scarring, with only four of them having vesicoureteral reflux.
      CONCLUSION: The most frequent metabolic abnormalities in preschool-age children
      with urolithiasis were hyperuricosuria and hypocitraturia. A comprehensive
      investigation of stone disease in children presenting with hematuria and UTI is
      important to prevent the development of renal parenchymal scarring.

PMID- 24314603
TI  - Expanding the indications for laparoscopic retroperitoneal adrenalectomy:
      experience with 81 resections.
AB  - BACKGROUND: Laparoscopic retroperitoneal (RP) adrenalectomy has gained popularity
      as the preferred approach over transabdominal (TA) method; however, surgeons have
      been reluctant to offer this operation to obese patients because of the concerns
      over inadequate working space and overall perceived higher rate of complications.
      The aim of the present study was to evaluate the feasibility and safety of RP
      adrenalectomy compared with TA adrenalectomy, specifically in morbidly obese
      patients. METHODS: All laparoscopic adrenalectomies performed at our institution
      between 2004 and 2012 were reviewed retrospectively. Presenting features,
      operative characteristics, and postoperative outcomes were evaluated.
      Complications were graded using Clavien system. Continuous variables were
      compared using Student t-test. Categorical variables were compared using chi(2)
      test. Prediction models were constructed using linear or logistic regression as
      appropriate. RESULTS: Eighty-one RP and 130 TA procedures were performed, 26
      (12.3%) and 60 (28.4%), respectively in obese patients (BMI > 30). Among the
      obese patients, operative time and estimated blood loss were less for RP (90
      versus 130 min; P < 0.001 and 0 versus 50 mL; P < 0.001). Differences in the
      length of stay, overall mortality, incidence and severity of postoperative
      complications, and rates of readmission were not statistically significant
      between RP and TA procedures for all comers and in the obese patients.
      Controlling the operative characteristics and patient-specific factors, neither
      operative approach nor obesity was found to independently predict the
      postoperative complications. CONCLUSIONS: Laparoscopic RP adrenalectomy is a safe
      and feasible technique for obese patients. In the obese patients and for all
      comers, it offers shorter operative time, decreased estimated blood loss, with
      comparable length of stay and morbidity and mortality rates. We therefore
      recommend that this technique should be considered for patients undergoing
      adrenal resection.

PMID- 24314606
TI  - [Reducing activities that do not give value: the pending structural reform].

PMID- 24314605
TI  - Expectancies for smoking cessation among drug-involved smokers: implications for
      clinical practice.
AB  - Drug-involved smokers may be less motivated to quit smoking because they expect
      smoking cessation to occasion adverse outcomes (e.g., exacerbation of drug use).
      Non-treatment-seeking adult smokers from the community (N=507) reported drug
      involvement, expectancies for smoking abstinence via the Smoking Abstinence
      Questionnaire (SAQ), and motivation to quit smoking (desire to quit and
      abstinence goal). Mediation analyses evaluated the indirect effects of binge
      drinking, marijuana, cocaine, other stimulant, opiate, and barbiturate/other
      sedative involvement on motivation to quit smoking through the SAQ Adverse
      Outcomes scale. Adverse outcomes expectancies accounted for a reduced desire to
      quit smoking and a lower likelihood of endorsing a goal of complete smoking
      abstinence among those involved with binge drinking, marijuana, cocaine, other
      stimulants, opiates, and barbiturates/other sedatives. Drug-involved smokers'
      greater expectancies for adverse outcomes upon quitting smoking may deter smoking
      quit attempts. Interventions are encouraged to counteract the notion that smoking
      cessation jeopardizes sobriety. 

PMID- 24314607
TI  - Ruptured liver caused by peliosis hepatis.

PMID- 24314608
TI  - [Groove pancreatitis in the differential diagnosis of pancreatic adenocarcinoma].

PMID- 24314609
TI  - [Hepatic adenomatosis: a disease with controversial treatment].

PMID- 24314610
TI  - [Preoperative blood ordering in elective colon surgery: requirement or routine?].
AB  - BACKGROUND: Preoperative blood ordering is frequently in elective colon surgery,
      even for procedures that rarely require blood transfusion. Most often this
      procedure is performed without proper analysis of the real needs. The aim of this
      study was to evaluate the patients who receive transfusion and determining their
      associated factors. METHODS: Retrospective study of all consecutive patients
      scheduled for elective colon surgery was carried out at 2007-2012. Several
      clinico-pathological and surgical variables were analyzed and predictive blood
      transfusion indices such as the cross-matched/transfusion ratio (C/T ratio),
      transfusion index and transfusion probability were calculated. Patients were
      divided in 2 groups according have received perioperative surgical transfusion or
      not. RESULTS: There were 457 surgery patients. A total of 171 blood units, in a
      74 patients were perioperative transfused. Overall cross-matched transfused ratio
      was 5.34, the transfusion probability 162%, and the transfusion index 0.18.
      Variables that were significantly associated with receiving blood transfusion in
      a multivariable analysis were a preoperative haemoglobin level less than 10 g/dl
      (OR: 309.8; 95% CI: 52.7-985.2), chronic pulmonary obstructive disease (OR: 3.7;
      95% CI: 1.3-10.7), oral anticoagulant therapy (OR: 5.7; 95% CI: 1.7-19.4) and
      surgical time over 120 min (OR: 10.7; 95% CI: 4.7-24.1). CONCLUSIONS: Likelihood
      of receiving perioperative transfusion in elective colon surgery is very low.
      Among their associated factors, the haemoglobin level less than 10 g/dl is the
      one with strongest association. Those patients with such low preoperative
      haemoglobin level should not be scheduled for elective colon surgery until they
      received specific treatment.

PMID- 24314611
TI  - [An infarcted horseshoe kidney].

PMID- 24314612
TI  - [Hilar cholangiocarcinoma: The number of positive nodes and positive node/total
      node ratio is a significant prognostic factor for survival].
AB  - INTRODUCTION: Surgical treatment of hilar cholangiocarcinoma remains a challenge.
      Multiple prognostic factors have been proposed. The number of positive nodes and
      the ratio between positive lymph node and total lymph node (G+/Gt) are considered
      by some authors as the most important factor. MATERIAL AND METHODS: We analyzed a
      series of 58 patients with Klatskin tumors. We evaluated the prognostic factors
      and survival with emphasis on the prognostic impact of the number of positive
      nodes and its relation to total lymph nodes. RESULTS: Resectability was 78% with
      a 5-year survival of 32%. The median number of nodes examined was 9.5. No
      significant differences were found in several of the proposed prognostic factors.
      The presence of 2 or more positive nodes or a ratio G+/Gt >= 0.2 were found to be
      poor prognostic factors. CONCLUSION: The relationship between positive lymph
      nodes and total lymph nodes and the number of positive lymph nodes are important
      prognostic factors.

PMID- 24314613
TI  - Cholecystocolic fistula.

PMID- 24314614
TI  - Interpretation of EUROCARE-5.

PMID- 24314618
TI  - Promise of uterine transplant--myth or a reality?
AB  - The scientific basis of uterus transplantation has been developing in parallel to
      other organ transplants throughout the modern period of transplant medicine.
      Immunosuppression and surgical techniques have been adequate for at least a
      decade; ethics and society have been less clearly developed. To many observers,
      it is still unclear if the endeavor is an overall positive or negative. Although
      scientific and technical challenges have been overcome, the ethical
      determinations will be a dynamic process while more experience continues to be
      gained. The most significant experience still lacking is a term gestation.
      Undoubtedly during a nine-month gestation, unforeseen challenges will test
      scientific processes and ethical assumptions. Despite dozens of animal
      experiments and a few animal births, no human birth has occurred to allow any
      definitive conclusions. 

PMID- 24314619
TI  - Herbal preparations for the menopause: beyond isoflavones and black cohosh.
AB  - Complementary and alternative medicines (CAM) such as isoflavones and black
      cohosh are commonly used to deal with menopausal symptoms, but benefit a limited
      proportion of women. The aim of this minireview is to summarize the evidence of
      the efficacy and safety of other herbal preparations. Randomized controlled
      trials (RCTs) find that the extracts of Mediterranean pine bark
      (Pycnogenol((r))), linseed, and Lepididium meyenii (Maca) reduce vasomotor
      symptoms. The results of RCTs of the hop flavonoid 8-prenylnaringenin are
      conflicting. Animal and human studies suggest that Dioscorea villosa (Wild
      yam),and Broccoli may protect against osteoporosis and breast and gynecological
      cancers but further evidence is required. Linseed may protect against breast
      cancer but the results are conflicting. 

PMID- 24314620
TI  - High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy
      when added to endocrine therapy in luminal B HER2 negative and node-positive
      breast cancer.
AB  - BACKGROUND: The indication of adjuvant chemotherapy for patients with highly
      proliferative estrogen receptor-positive breast cancer is controversial. We
      analyzed the predictive value of Ki67 for the efficacy of adjuvant chemotherapy
      in patients with estrogen receptor-positive, node-positive breast cancer.
      PATIENTS AND METHODS: We identified 1241 patients with Luminal B early stage
      breast cancer with 1-3 axillary positive nodes who underwent surgery between 1995
      and 2005 at the European Institute of Oncology and received adjuvant
      hormonotherapy and/or chemotherapy. Differences in the distribution of
      characteristics according to treatment were evaluated by the Chi-square test. To
      evaluate the effect of adding chemotherapy to hormonotherapy, the propensity
      score method was used to match patients' characteristics minimizing bias related
      to the non-random assignment of treatment. RESULTS: The probability of receiving
      chemotherapy was significantly associated with age, tumor grade, degree of
      hormone responsiveness, tumor size and peripheral vascular invasion. The
      propensity score distribution was statistically different between the two
      treatment groups (p < 0.0001). The 5-year OS percentages were 95.8% (95% CI, 93.5
      97.2) in the hormonotherapy group and 96.2% (95%CI, 94.4-97.4%) in the
      hormonotherapy/chemotherapy group (log-rank test p-value 0.663). The 5-year DFS
      percentages were 84.6% (95% CI, 81.0-87.6%) in the hormonotherapy group and 84.2%
      (95% CI, 81.3-86.7%) in the hormonotherapy/chemotherapy group (log-rank test p
      value 0.388). However, when analyzing the 5-year DFS by Ki-67 distribution,
      Subpopulation Treatment Effect Pattern Plot (STEPP) analysis showed a beneficial
      effect of chemotherapy in patients with highly proliferative tumor (Ki-67 >=
      32%). The interaction between Ki-67 and treatment was statistically significant
      (p = 0.027). CONCLUSIONS: Ki67 expression identifies a subset of patients with
      Luminal B and node-positive breast cancer who could benefit from addition of
      adjuvant chemotherapy to hormonotherapy. Dichotomy was observed for Ki67 at 32%
      level.

PMID- 24314615
TI  - Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a
      population-based study.
AB  - BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care
      systems. EUROCARE-the largest cooperative study of population-based cancer
      survival in Europe-has shown persistent differences between countries for cancer
      survival, although in general, cancer survival is improving. Major changes in
      cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s.
      EUROCARE-5 assesses their effect on cancer survival in 29 European countries.
      METHODS: In this retrospective observational study, we analysed data from 107
      cancer registries for more than 10 million patients with cancer diagnosed up to
      2007 and followed up to 2008. Uniform quality control procedures were applied to
      all datasets. For patients diagnosed 2000-07, we calculated 5-year relative
      survival for 46 cancers weighted by age and country. We also calculated country
      specific and age-specific survival for ten common cancers, together with survival
      differences between time periods (for 1999-2001, 2002-04, and 2005-07). FINDINGS:
      5-year relative survival generally increased steadily over time for all European
      regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer
      (73.4% [95% CI 72.9-73.9] vs 81.7% [81.3-82.1]), non-Hodgkin lymphoma (53.8%
      [53.3-54.4] vs 60.4% [60.0-60.9]), and rectal cancer (52.1% [51.6-52.6] vs 57.6%
      [57.1-58.1]). Survival in eastern Europe was generally low and below the European
      mean, particularly for cancers with good or intermediate prognosis. Survival was
      highest for northern, central, and southern Europe. Survival in the UK and
      Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin
      melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon,
      and lung cancers. Survival for lung cancer in the UK and Ireland was much lower
      than for other regions for all periods, although results for lung cancer in some
      regions (central and eastern Europe) might be affected by overestimation.
      Survival usually decreased with age, although to different degrees depending on
      region and cancer type. INTERPRETATION: The major advances in cancer management
      that occurred up to 2007 seem to have resulted in improved survival in Europe.
      Likely explanations of differences in survival between countries include:
      differences in stage at diagnosis and accessibility to good care, different
      diagnostic intensity and screening approaches, and differences in cancer biology.
      Variations in socioeconomic, lifestyle, and general health between populations
      might also have a role. Further studies are needed to fully interpret these
      findings and how to remedy disparities. FUNDING: Italian Ministry of Health,
      European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.

PMID- 24314616
TI  - Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5--a
      population-based study.
AB  - BACKGROUND: Survival and cure rates for childhood cancers in Europe have greatly
      improved over the past 40 years and are mostly good, although not in all European
      countries. The EUROCARE-5 survival study estimates survival of children diagnosed
      with cancer between 2000 and 2007, assesses whether survival differences among
      European countries have changed, and investigates changes from 1999 to 2007.
      METHODS: We analysed survival data for 157,499 children (age 0-14 years)
      diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population
      based cancer registries in 29 countries. We calculated observed, country-weighted
      1-year, 3-year, and 5-year survival for major cancers and all cancers combined.
      For comparison between countries, we used the corrected group prognosis method to
      provide survival probabilities adjusted for multiple confounders (sex, age,
      period of diagnosis, and, for all cancers combined without CNS cancers, casemix).
      Age-adjusted survival differences by area and calendar period were calculated
      with period analysis and were given for all cancers combined and the major
      cancers. FINDINGS: We analysed 59,579 cases. For all cancers combined for
      children diagnosed in 2000-07, 1-year survival was 90.6% (95% CI 90.2-90.9), 3
      year survival was 81.0 % (95% CI 80.5-81.4), and 5-year survival was 77.9% (95%
      CI 77.4-78.3). For all cancers combined, 5-year survival rose from 76.1% (74.4
      77.7) for 1999-2001, to 79.1% (77.3-80.7) for 2005-07 (hazard ratio 0.973, 95% CI
      0.965-0.982, p<0.0001). The greatest improvements were in eastern Europe, where 5
      year survival rose from 65.2% (95% CI 63.1-67.3) in 1999-2001, to 70.2% (67.9
      72.3) in 2005-07. Europe-wide average yearly change in mortality (hazard ratio)
      was 0.939 (95% CI 0.919-0.960) for acute lymphoid leukaemia, 0.959 (0.933-0.986)
      for acute myeloid leukaemia, and 0.940 (0.897-0.984) for non-Hodgkin lymphoma.
      Mortality for all of Europe did not change significantly for Hodgkin's lymphoma,
      Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma,
      osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted
      between countries and regions, ranging from 70% to 82% (for 2005-07).
      INTERPRETATION: Several reasons might explain persisting inequalities. The lack
      of health-care resources is probably most important, especially in some eastern
      European countries with limited drug supply, lack of specialised centres with
      multidisciplinary teams, delayed diagnosis and treatment, poor management of
      treatment, and drug toxicity. In the short term, cross-border care and
      collaborative programmes could help to narrow the survival gaps in Europe.
      FUNDING: Italian Ministry of Health, European Commission, Compagnia di San Paolo
      Foundation.

PMID- 24314621
TI  - Influenza vaccination and the end of simplicity.

PMID- 24314623
TI  - Use of health care services by people with mental illness: secondary data from
      three statutory health insurers and the German Statutory Pension Insurance
      Scheme.
AB  - BACKGROUND: A discipline- and sector-specific analysis of health-care utilization
      by persons with mental illness in Germany is an indispensable aid to planning for
      the provision of adequate basic care. METHOD: Secondary data from three statutory
      health insurers and the German Statutory Pension Insurance Scheme for the period
      2005-2007 were evaluated to identify insurees with mental illness (ICD-10
      diagnosis groups F0-F5). RESULTS: In the period 2005-2007, 3.28 million (33%) of
      9.92 million insurees had at least one contact with the health-care system in
      which a mental disorder was diagnosed. 50.4% (1,651,367) of these insurees had at
      least two mental disorders. Nearly all (98.8%) of the insurees with a psychiatric
      index diagnosis had at least one somatic diagnosis coded as well. 95.7% of
      treatments were provided in the outpatient setting. Somatic medical specialties
      provided the majority of treatments both in ambulatory care and in the hospital.
      For example, 77.5% of persons with severe depression were treated with five kinds
      of treatment that were provided exclusively by primary care physicians and other
      specialists in somatic medicine in private practice, sometimes in combination
      with psychiatric treatment or psychotherapy. CONCLUSION: There was a high degree
      of comorbidity of mental and somatic illness. The fact that the vast majority of
      treatment was provided in the outpatient setting implies that cooperation across
      health-care sectors and disciplines should be reinforced, and that measures
      should be taken to ensure the adequate delivery of basic psychiatric care by
      primary care physicians.

PMID- 24314622
TI  - Targeted vaccine selection in influenza vaccination.
AB  - BACKGROUND: The main target groups for influenza vaccination are the elderly, the
      chronically ill, infants, and toddlers. Influenza vaccines are needed that suit
      the immunological particularities of each of these age and risk groups. Recent
      years have seen the approval of influenza vaccines that are more immunogenic than
      before, but whose use in Germany is limited by the restriction of reimbursement
      to a small number of vaccines. METHODS: The Medline database was selectively
      searched for pertinent literature. RESULTS: The suboptimal immunogenicity of
      conventional influenza vaccines that contain inactivated viral cleavage products
      and subunits can be markedly improved by the use of squalene-based adjuvant
      systems, by the integration of viral antigens in virosomal particles, or by
      intradermal administration. The vaccination of elderly persons with a vaccine
      containing the adjuvant MF59 was found to lower the risk of hospitalization for
      influenza or pneumonia by 25% compared to vaccination with a trivalent
      inactivated vaccine (TIV). On the other hand, the adjuvant ASO3 was found to be
      associated with an up to 17-fold increase in the frequency of narcolepsy among 4-
      to 18-year-olds. In a prospective study, a virosomal vaccine lowered the
      frequency of laboratory-confirmed influenza in vaccinated children by 88%
      compared to unvaccinated children (2 versus 18 cases per 1000 individuals). A
      live, attenuated influenza vaccine lowered the rate of disease in children up to
      age 7 by 48% compared to a TIV (4.2% versus 8.1%). CONCLUSION: The newer vaccines
      possess improved efficacy when used for primary and booster immunization in
      certain age and risk groups, and they are superior in this respect to
      conventional vaccines based on viral cleavage products and subunits. The
      risk/benefit profiles of all currently available vaccines vary depending on the
      age group or risk group in which they are used.

PMID- 24314624
TI  - Impacts of drug reimbursement reductions on utilization and expenditures of oral
      antidiabetic medications in Taiwan: an interrupted time series study.
AB  - OBJECTIVES: To control increasing pharmaceutical expenditures, Taiwan's National
      Health Insurance has implemented a series of drug reimbursement price reductions
      since 2000. This study examined changes in use and expenditures of oral
      antidiabetic medications following the price regulation in November 2006.
      METHODS: We obtained claims data between January 2006 and August 2007 from
      Taiwan's National Health Insurance Research Database. We categorized oral
      antidiabetic products as affected by the reimbursement reduction ("targeted") or
      not ("non-targeted"), by level of relative price reduction, and by manufacturer
      type (international vs. local manufacturers). We used an interrupted time series
      design and segmented regression models to estimate changes in monthly per capita
      prescribing rate, volume, and insurance reimbursement expenditures following the
      policy. RESULTS: The majority (129/178; 72.5%) of oral antidiabetic products were
      targeted by this round of price reductions. There was a relative reduction of
      9.5% [95%CI: -12.68, -6.32] in total expenditures at ten months post-policy
      compared to expected rates. For targeted products, there were 2.04% [95%CI: 
      4.15, 0.07] and 13.26% [95%CI: -16.64, -9.87] relative reductions in prescribing
      rate and expenditures, respectively, at ten months post-policy. Non-targeted
      products increased significantly (22% [95%CI: 10.49, 33.51] and 22.85% [95%CI:
      11.69, 34.01] relative increases in prescribing rate and expenditures
      respectively). Larger reimbursement cuts led to greater reductions in prescribing
      rate, volume, and insurance reimbursement expenditures of targeted products.
      Prescribing rates of both targeted and non-targeted products by international
      manufacturers declined after the policy while rates of prescribing non-targeted
      products by local manufacturers increased. CONCLUSIONS: While total government
      expenditures for oral antidiabetic medications were contained by the policy, our
      results indicate that prescribing shifted at the margin from targeted to non
      targeted products and from international to local products. Further research is
      warranted to understand how changes in medication use due to price regulation
      policies affect medication adherence and patient health outcomes.

PMID- 24314625
TI  - Access to innovation: is there a difference in the use of expensive anticancer
      drugs between French hospitals?
AB  - In DRG-based hospital payment systems, expensive drugs are often funded
      separately. In France, specific expensive drugs (including a large proportion of
      anticancer drugs) are fully reimbursed up to national reimbursement tariffs to
      ensure equity of access. Our objective was to analyse the use of expensive
      anticancer drugs in public and private hospitals, and between regions. We had
      access to sales per anticancer drug and per hospital in the year 2008. We used a
      multilevel model to study the variation in the mean expenditure of expensive
      anticancer drugs per course of chemotherapy and per hospital. The mean
      expenditure per course of chemotherapy was ?922 [95% CI: 890-954]. At the
      hospital level, specialisation in chemotherapies for breast cancers was
      associated with a higher expenditure of anticancer drugs per course for those
      hospitals with the highest proportion of cancers at this site. There were no
      differences in the use of expensive drugs between the private and the public
      hospital sector after controlling for case mix. There were no differences between
      the mean expenditures per region. The absence of disparities in the use of
      expensive anticancer drugs between hospitals and regions may indicate that
      exempting chemotherapies from DRG-based payments and providing additional
      reimbursement for these drugs has been successful at ensuring equal access to
      care. 

PMID- 24314626
TI  - Hospital restructuring and physician job satisfaction: an empirical study.
AB  - The adoption of clinical directorates through the internal reconfiguration of
      hospital organizations has been one of the most widespread restructuring
      interventions in many Western European countries. Despite its extensive adoption,
      a lack of knowledge remains on the analysis of how this reorganization affects
      professionals' job satisfaction. This paper contributes to the debate on clinical
      directorates by exploring how the structural characteristics of newly adopted
      organizational models influence physician's job satisfaction. More than 300
      physicians in 18 clinical directorates in the Italian National Health Service
      were surveyed regarding their overall job satisfaction following the introduction
      of departmental arrangements. Survey results were then linked to another survey
      that classified newly adopted models according to the criteria used to merge
      hospital wards into directorates, by recognizing "Process-integration",
      "Specialty-integration" and "Mixed-integration" types of directorates. Our
      findings show that structural aspects of change significantly influenced overall
      job satisfaction, and that a physician's openness to experience moderated the
      adoption and implementation of new clinical directorates. Specifically, results
      demonstrate that physicians with high openness to experience scores were more
      receptive to the positive impacts of change on overall job satisfaction.
      Implications for how these findings may facilitate organizational shifts within
      hospital settings are discussed. 

PMID- 24314627
TI  - Re. 'Computed tomography imaging features and classification of isolated
      dissection of the superior mesenteric artery'.

PMID- 24314628
TI  - Reply to Dr. Marques do Santos' letter - should we treat asymptomatic patients
      with mildly ulcerated terminal ileum?

PMID- 24314629
TI  - Lead gunshot pellet ingestion and tissue lead levels in wild ducks from Argentine
      hunting hotspots.
AB  - Lead poisoning in waterfowl due to ingestion of lead pellets is a long recognized
      worldwide problem but poorly studied in South America, particularly in
      Argentinean wetlands where duck hunting with lead gunshot is extensive. In 2008,
      we found high pellet ingestion rates in a small sample of hunted ducks. To expand
      our knowledge on the extent of lead exposure and to assess health risks from
      spent shot intake, during 2011 and 2012 we sampled 415 hunter-killed ducks and 96
      live-trapped ducks. We determined the incidence of lead shot ingestion and lead
      concentrations in bone, liver and blood in five duck species: whistling duck
      (Dendrocygna bicolor), white-faced tree duck (D. viduata), black-bellied
      whistling-duck (D. autumnalis), rosy-billed pochard (Netta peposaca) and
      Brazilian duck (Amazonetta brasiliensis). The ingestion of lead shot was
      confirmed in 10.4% of the ducks examined (43/415), with a prevalence that varied
      by site and year, from 7.6% to 50%. All bone samples (n=382) and over 60% of
      liver samples (249/412) contained lead concentrations above the detection limit.
      The geometric mean lead concentration in tissues (mg/kg dry weight) was 0.31
      (GSD=3.93) and 3.61 (GSD=4.02) for liver and bone, respectively, and 0.20
      (GSD=2.55) in blood (mg/kg wet weight). Lead levels surpassed toxicity thresholds
      at which clinical poisoning is expected in 3.15% of liver samples, 23.8% of bones
      and 28% of blood samples. Ducks with ingested lead pellets were much more likely
      to have high levels of lead in their liver. Rosy-billed pochards were
      consistently more prone to ingesting lead shot than other duck species sampled.
      However, whistling ducks showed higher levels of lead in liver and bone. Our
      results suggest that lead from ammunition could become a substantial threat for
      the conservation of wild duck populations in Argentina. The replacement of lead
      by non-toxic shot would be a reasonable and effective solution to this problem. 

PMID- 24314630
TI  - The role of hematopoietic cell transplantation in adult ALL: clinical equipoise
      persists.
AB  - Adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1)
      may be treated either with ongoing systemic chemotherapy or with allogeneic
      hematopoietic cell transplantation (alloHCT). Despite the presence of phase III
      trials to support clinical decision-making, we hypothesized that physicians who
      treat adult ALL would demonstrate wide practice variation. Canadian hematologists
      who treat ALL were surveyed electronically. Overall, 69 of 173 physicians
      responded (40%). There was high agreement with offering alloHCT for ALL with high
      risk cytogenetics or induction failure after a single chemotherapy cycle.
      However, only a minority of respondents felt that age >35 years was an indication
      for alloHCT in CR1. Almost all respondents (96%) felt that a well-matched
      unrelated donor was an acceptable alternative to a sibling donor. There was
      uncertainty about the role of cord blood (53% agree) and the utility of reduced
      intensity conditioning HCT (41% agree). In contrast to the results of the
      MRC/ECOG study, respondents considered alloHCT to be particularly helpful in high
      risk patients. Consensus was lacking on the use of cord blood, RIC alloHCT, and
      the application of MRD. Equipoise exists on the role of alloHCT in CR1 in ALL,
      suggesting that further trials in this area are required. 

PMID- 24314631
TI  - Role of the cytosolic tails of Rift Valley fever virus envelope glycoproteins in
      viral morphogenesis.
AB  - The correct folding, heterodimerization and trafficking of Gn/Gc envelope
      glycoproteins of Rift Valley fever virus, RVFV (Bunyaviridae and Phlebovirus
      genus) are essential for Golgi assembly and budding of viral particles. The Gn
      and Gc carboxy-terminus contain a Golgi targeting and an ER-retrieval signal,
      respectively. We generated RVFV-like particles with mutations in the cytosolic
      tails of Gn or Gc and identified regions important for release of infectious
      particles. The role of specific amino-acids in these regions was further
      investigated by creating recombinant mutant viruses by reverse-genetics. Residues
      outside the suspected Golgi targeting motif, i.e. the di-lysine K29-K30 motif and
      the N43, R44 and I46 residues of the Gn cytosolic domain, appeared important for
      Golgi localization and RNP packaging. Concerning the Gc tail, replacement of K2
      or K3 in the di-lysine motif, had a drastic impact on Gn trafficking and induced
      an important organelle redistribution and cell remodeling, greatly affecting
      particle formation and release.

PMID- 24314632
TI  - Dengue virus subgenomic RNA induces apoptosis through the Bcl-2-mediated PI3k/Akt
      signaling pathway.
AB  - We report a RNA species of 429 nucleotides derived from the 3' untranslated
      region of the viral genome in Dengue 2 virus (DENV-2) infected cells. The 3'
      terminal of viral RNA contained specific conserved structures that are important
      for the production of subgenomic RNA. Transient replicon assays suggested that
      loss of this small RNA has little effect on viral replication, and genetic
      analysis using recombinant viruses demonstrated that the existence of this
      subgenomic RNA is not essential for the life cycle of the DENV-2. Results from
      cytotoxicity and apoptosis assay revealed that the generation of subgenomic RNA
      is significant for DENV-2 viral cytopathicity and virus-induced apoptosis; and
      the deficiency could be partially restored by providing subgenomic RNA in trans
      from transfection. In addition, we found that subgenomic RNA modulates the
      phosphatidylinositol 3-kinase (PI3k)/Akt signaling pathway through a Bcl-2
      related mechanism, resulting in apoptotic cell death.

PMID- 24314633
TI  - Mapping of the receptor-binding domain and amino acids critical for attachment in
      the spike protein of avian coronavirus infectious bronchitis virus.
AB  - The infection of the avian coronavirus infectious bronchitis virus (IBV) is
      initiated by the binding of the spike glycoprotein S to sialic acids on the
      chicken host cell. In this study we identified the receptor-binding domain (RBD)
      of the spike of the prototype IBV strain M41. By analyzing the ability of
      recombinantly expressed chimeric and truncated spike proteins to bind to chicken
      tissues, we demonstrate that the N-terminal 253 amino acids of the spike are both
      required and sufficient for binding to chicken respiratory tract in an alpha-2,3
      sialic acid-dependent manner. Critical amino acids for attachment of M41 spike
      are present within the N-terminal residues 19-69, which overlap with a
      hypervariable region in the S1 gene. Our results may help to understand the
      differences between IBV S1 genotypes and the ultimate pathogenesis of IBV in
      chickens.

PMID- 24314634
TI  - Human herpesvirus-6B protein U19 contains a p53 BOX I homology motif for HDM2
      binding and p53 stabilization.
AB  - In order to establish a successful infection, it is of crucial importance for
      invading viruses to alter the activities of the regulatory protein p53. Beta
      herpesviruses stabilize p53 and likely direct its activities towards generation
      of a replication-friendly environment. We here study the mechanisms behind HHV-6B
      induced stabilization and inactivation of p53. Stable transgene expression of the
      HHV-6B protein U19 was sufficient to achieve upregulation of p53. U19 bound
      directly to the p53-regulating protein HDM2 in vitro, co-precipitated together
      with HDM2 in lysates, and co-localized with HDM2 in the nucleus when
      overexpressed. U19 contained a sequence with a putative p53 BOX I-motif for HDM2
      binding. Mutation of the two key amino acids within this motif was sufficient to
      inhibit all the described U19 functions. Our study provides further insight into
      p53-modulating strategies used by herpesviruses and elucidates a mechanism used
      by HHV-6B to circumvent the antiviral response.

PMID- 24314635
TI  - Methylation of translation elongation factor 1A by the METTL10-like See1
      methyltransferase facilitates tombusvirus replication in yeast and plants.
AB  - Replication of tombusviruses and other plus-strand RNA viruses depends on several
      host factors that are recruited into viral replicase complexes. Previous studies
      have shown that eukaryotic translation elongation factor 1A (eEF1A) is one of the
      resident host proteins in the highly purified tombusvirus replicase complex. In
      this paper, we show that methylation of eEF1A by the METTL10-like See1p
      methyltransferase is required for tombusvirus and unrelated nodavirus RNA
      replication in yeast model host. Similar to the effect of SEE1 deletion, yeast
      expressing only a mutant form of eEF1A lacking the 4 known lysines subjected to
      methylation supported reduced TBSV accumulation. We show that the half-life of
      several viral replication proteins is decreased in see1Delta yeast or when a
      mutated eEF1A was expressed as a sole source for eEF1A. Silencing of the plant
      ortholog of See1 methyltransferase also decreased tombusvirus RNA accumulation in
      Nicotiana benthamiana.

PMID- 24314636
TI  - Virus-encoded miR-155 ortholog is an important potential regulator but not
      essential for the development of lymphomas induced by very virulent Marek's
      disease virus.
AB  - The microRNA (miRNA) mdv1-miR-M4, a functional miR-155 ortholog encoded by
      oncogenic Marek's disease virus (MDV), has previously been suggested to be
      involved in MDV pathogenesis. Using the technique of bacterial artificial
      chromosome mutagenesis, we have presently evaluated the potential role of mdv1
      miR-M4 in the oncogenesis of the very virulent (vv) MDV strain GX0101.
      Unexpectedly, deletions of the Meq-cluster or mdv1-miR-M4 alone from the viral
      genome strongly decreased rather than abolished its oncogenicity. Compared to
      GX0101, mortalities of mutants GXDeltamiR-M4 and GXDeltaMeq-miRs were reduced
      from 100% to 18% and 4%, coupled with the gross tumor incidence reduction from
      28% to 22% and 8%, respectively. Our data suggests that the mdv1-miR-M4 is
      possibly an important regulator in the development of Marek's disease (MD)
      lymphomas but is not essential for the oncogenicity of vvMDV. In addition, some
      of the other Meq-clustered miRNAs may also play potentially critical roles in
      vvMDV induction of lymphomas.

PMID- 24314637
TI  - A novel small animal model to study the replication of simian foamy virus in
      vivo.
AB  - Preclinical evaluation in a small animal model would help the development of gene
      therapies and vaccines based on foamy virus vectors. The establishment of
      persistent, non-pathogenic infection with the prototype foamy virus in mice and
      rabbits has been described previously. To extend this spectrum of available
      animal models, hamsters were inoculated with infectious cell supernatant or
      bioballistically with a foamy virus plasmid. In addition, a novel foamy virus
      from a rhesus macaque was isolated and characterised genetically. Hamsters and
      mice were infected with this new SFVmac isolate to evaluate whether hamsters are
      also susceptible to infection. Both hamsters and mice developed humoral responses
      to either virus subtype. Virus integration and replication in different animal
      tissues were analysed by PCR and co-cultivation. The results strongly indicate
      establishment of a persistent infection in hamsters. These studies provide a
      further small animal model for studying FV-based vectors in addition to the
      established models.

PMID- 24314638
TI  - Severe pathogenesis of influenza B virus in pregnant mice.
AB  - The study on pathogenesis of influenza B virus during pregnancy is limited. Here,
      we showed using a mouse model that influenza B virus could cause severe disease
      including death during pregnancy. Infected pregnant mice resulted in 40%
      mortality, but infected age-matched non-pregnant mice did not show any death.
      Infected pregnant mice contained high viral loads in lungs with the elevated
      inductions of inflammatory cytokines and chemokines than infected non-pregnant
      mice. Infected pregnant mice delivered lower number of neonates than uninfected
      pregnant mice, suggesting adverse effects of influenza B virus on fetuses.
      Progesterone which is important for maintaining pregnancy was reduced in uteruses
      of infected pregnant mice than in those of uninfected pregnant mice. Taken
      together, our results suggest that influenza B virus can cause severe disease
      during pregnancy, and that preventive measures including vaccination may be
      important for protecting women during pregnancy.

PMID- 24314639
TI  - Modeling of the human rhinovirus C capsid suggests possible causes for antiviral
      drug resistance.
AB  - Human rhinoviruses of the RV-C species are recently discovered pathogens with
      greater clinical significance than isolates in the RV-A+B species. The RV-C
      cannot be propagated in typical culture systems; so much of the virology is
      necessarily derivative, relying on comparative genomics, relative to the better
      studied RV-A+B. We developed a bioinformatics-based structural model for a C15
      isolate. The model showed the VP1-3 capsid proteins retain their fundamental
      cores relative to the RV-A+B, but conserved, internal RV-C residues affect the
      shape and charge of the VP1 hydrophobic pocket that confers antiviral drug
      susceptibility. When predictions of the model were tested in organ cultures or
      ALI systems with recombinant C15 virus, there was a resistance to capsid-binding
      drugs, including pleconaril, BTA-188, WIN56291, WIN52035 and WIN52084. Unique to
      all RV-C, the model predicts conserved amino acids within the pocket and capsid
      surface pore leading to the pocket may correlate with this activity.

PMID- 24314640
TI  - Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene
      signature in primary human bronchial epithelial cells downstream of membrane
      fusion.
AB  - Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than
      previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of
      inflammatory activation in respiratory epithelial cells during H1N1pdm infection
      are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus
      entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm
      infection rapidly initiated a robust inflammatory gene signature (3 h post
      infection) not elicited by sH1N1 infection. Protein secretion inhibition had no
      effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed
      to induce robust inflammatory gene expression which was rescued with restoration
      of fusion ability, suggesting H1N1pdm directly triggered the inflammatory
      signature downstream of membrane fusion. Investigation of intra-virion components
      revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype
      than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater
      inflammatory gene expression than sH1N1 in vitro due to direct virus-epithelial
      cell interaction.

PMID- 24314641
TI  - The West Nile virus assembly process evades the conserved antiviral mechanism of
      the interferon-induced MxA protein.
AB  - Flaviviruses have evolved means to evade host innate immune responses. Recent
      evidence suggests this is due to prevention of interferon production and
      signaling in flavivirus-infected cells. Here we show that the interferon-induced
      MxA protein can sequester the West Nile virus strain Kunjin virus (WNVKUN) capsid
      protein in cytoplasmic tubular structures in an expression-replication system.
      This sequestering resulted in reduced titers of secreted WNVKUN particles. We
      show by electron microscopy, tomography and 3D modeling that these cytoplasmic
      tubular structures form organized bundles. Additionally we show that recombinant
      ER-targeted MxA can restrict production of infectious WNVKUN under conditions of
      virus infection. Our results indicate a co-ordinated and compartmentalized WNVKUN
      assembly process may prevent recognition of viral components by MxA, particularly
      the capsid protein. This recognition can be exploited if MxA is targeted to
      intracellular sites of WNVKUN assembly. This results in further understanding of
      the mechanisms of flavivirus evasion from the immune system.

PMID- 24314642
TI  - The stability of secreted, acid-labile H77/JFH-1 hepatitis C virus (HCV)
      particles is altered by patient isolate genotype 1a p7 sequences.
AB  - Secreted infectious particles generated by the genotype 2a JFH-1 hepatitis C
      virus infectious clone are resistant to acidic pH, whereas intracellular virions
      remain acid-labile. Thus, JFH-1 particles are thought to undergo pH maturation as
      they are secreted from the cell. Here, we demonstrate that both infectious
      intracellular and secreted genotype 1a (H77)/JFH-1 chimaeric particles display
      enhanced acid sensitivity compared with JFH-1, although pH maturation still
      occurs upon release. Introduction of p7 sequences from genotype 1a infected HCV
      patients into the H77/JFH-1 background yielded variable effects on infectious
      particle production and sensitivity to small molecule inhibitors. However, two
      selected patient p7 sequences increased the acid stability of secreted, but not
      intracellular H77/JFH-1 particles, suggesting that p7 directly influences
      particle pH maturation via an as yet undefined mechanism. We propose that HCV
      particles vary in acid stability, and that this may be dictated by variations in
      both canonical structural proteins and p7.

PMID- 24314643
TI  - Insertion of myeloid-active elements into the human cytomegalovirus major
      immediate early promoter is not sufficient to drive its activation upon infection
      of undifferentiated myeloid cells.
AB  - The Major Immediate Early Promoter (MIEP) of human cytomegalovirus (HCMV)
      controls viral Immediate Early (IE) gene expression, which must be activated to
      initiate productive infection and repressed to establish latency. Regulation of
      the MIEP is critical for both viral spread and persistence. In addition to the
      Daxx-mediated intrinsic cellular defense that regulates the MIEP, the cell-type
      specific balance between cellular activators and repressors of the promoter may
      help dictate whether viral IE genes will be expressed or silenced. For example,
      in undifferentiated myeloid cells, transcriptional repressors of the MIEP may
      outnumber transcriptional activators, leading to promoter silencing and latency
      establishment. We created a recombinant viral genome in which a myeloid-active
      promoter replaced part of the MIEP. The viable virus generated failed to express
      the viral IE genes in an undifferentiated myeloid cell line. These observations
      have mechanistic implications regarding how viral IE gene expression is regulated
      during latency.

PMID- 24314644
TI  - Amino acids 78 and 79 of Mammalian Orthoreovirus protein uNS are necessary for
      stress granule localization, core protein lambda2 interaction, and de novo virus
      replication.
AB  - At early times in Mammalian Orthoreovirus (MRV) infection, cytoplasmic inclusions
      termed stress granules (SGs) are formed as a component of the innate immune
      response, however, at later times they are no longer present despite continued
      immune signaling. To investigate the roles of MRV proteins in SG modulation we
      examined non-structural protein uNS localization relative to SGs in infected and
      transfected cells. Using a series of mutant plasmids, we mapped the necessary
      MUNS residues for SG localization to amino acids 78 and 79. We examined the
      capacity of a MUNS(78-79) mutant to associate with known viral protein binding
      partners of MUNS and found that it loses association with viral core protein
      lambda2. Finally, we show that while this mutant cannot support de novo viral
      replication, it is able to rescue replication following siRNA knockdown of MUNS.
      These data suggest that MUNS association with SGs, lambda2, or both play roles in
      MRV replication.

PMID- 24314646
TI  - Chimeric SV40 virus-like particles induce specific cytotoxicity and protective
      immunity against influenza A virus without the need of adjuvants.
AB  - Virus-like particles (VLPs) are a promising vaccine platform due to the safety
      and efficiency. However, it is still unclear whether polyomavirus-based VLPs are
      useful for this purpose. Here, we attempted to evaluate the potential of
      polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We
      constructed chimeric SV40-VLPs carrying an HLA-A*02:01-restricted, cytotoxic T
      lymphocyte (CTL) epitope derived from influenza A virus. HLA-A*02:01-transgenic
      mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs
      effectively induced influenza-specific CTLs and heterosubtypic protection against
      influenza A viruses without the need of adjuvants. Because DNase I treatment of
      the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant
      property may not result from DNA contaminants in the VLP preparation. In
      addition, immunization with the chimeric SV40-VLPs generated long-lasting memory
      CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a
      promising CTL-based vaccine platform with self-adjuvant properties.

PMID- 24314645
TI  - Enhanced arbovirus surveillance with deep sequencing: Identification of novel
      rhabdoviruses and bunyaviruses in Australian mosquitoes.
AB  - Viral metagenomics characterizes known and identifies unknown viruses based on
      sequence similarities to any previously sequenced viral genomes. A metagenomics
      approach was used to identify virus sequences in Australian mosquitoes causing
      cytopathic effects in inoculated mammalian cell cultures. Sequence comparisons
      revealed strains of Liao Ning virus (Reovirus, Seadornavirus), previously
      detected only in China, livestock-infecting Stretch Lagoon virus (Reovirus,
      Orbivirus), two novel dimarhabdoviruses, named Beaumont and North Creek viruses,
      and two novel orthobunyaviruses, named Murrumbidgee and Salt Ash viruses. The
      novel virus proteomes diverged by >= 50% relative to their closest previously
      genetically characterized viral relatives. Deep sequencing also generated genomes
      of Warrego and Wallal viruses, orbiviruses linked to kangaroo blindness, whose
      genomes had not been fully characterized. This study highlights viral
      metagenomics in concert with traditional arbovirus surveillance to characterize
      known and new arboviruses in field-collected mosquitoes. Follow-up
      epidemiological studies are required to determine whether the novel viruses
      infect humans.

PMID- 24314647
TI  - Deamination intensity profiling of human APOBEC3 protein activity along the near
      full-length genomes of HIV-1 and MoMLV by HyperHRM analysis.
AB  - Enzymatic deamination of cytidines in DNA is an intrinsic component of antibody
      maturation and retroviral resistance, but can also be a source of HIV drug
      resistance and cancer-causing mutations. Here, we developed a high-throughput
      method based on high resolution melt (HRM) analysis called HyperHRM that can
      screen genomic DNA for rare hypermutated proviral sequences and accurately
      quantify the number of C-to-T or G-to-A mutations in each sequence. We
      demonstrate the effectiveness of the approach by profiling in parallel the
      intensity of the DNA mutator activity of all seven human APOBEC3 proteins on the
      near full-length sequence of HIV-1 and the Moloney murine leukemia virus.
      Additionally, HRM was successfully used to identify hypermutated proviral
      sequences in peripheral blood mononuclear cells from an HIV-1 patient. These
      results exemplify the effectiveness of HRM-based approaches for hypermutation
      quantification and for the detection of hypermutated DNA sequences potentially
      associated with disease or retroviral drug resistance.

PMID- 24314648
TI  - Modeling of the human rhinovirus C capsid suggests a novel topography with
      insights on receptor preference and immunogenicity.
AB  - Features of human rhinovirus (RV)-C virions that allow them to use novel cell
      receptors and evade immune responses are unknown. Unlike the RV-A+B, these
      isolates cannot be propagated in typical culture systems or grown for structure
      studies. Comparative sequencing, I-TASSER, MODELLER, ROBETTA, and refined
      alignment techniques led to a structural approximation for C15 virions, based on
      the extensive, resolved RV-A+B datasets. The model predicts that all RV-C VP1
      proteins are shorter by 21 residues relative to the RV-A, and 35 residues
      relative to the RV-B, effectively shaving the RV 5-fold plateau from the
      particle. There are major alterations in VP1 neutralizing epitopes and the
      structural determinants for ICAM-1 and LDLR receptors. The VP2 and VP3 elements
      are similar among all RV, but the loss of sequence "words" contributing Nim1ab
      has increased the apparent selective pressure among the RV-C to fix mutations
      elsewhere in the VP1, creating a possible compensatory epitope.

PMID- 24314649
TI  - Induction of conformational changes at the N-terminus of herpes simplex virus
      glycoprotein D upon binding to HVEM and nectin-1.
AB  - Herpes simplex virus entry is initiated by glycoprotein D (gD) binding to a
      cellular receptor, such as HVEM or nectin-1. gD is activated by receptor-induced
      displacement of the C-terminus from the core of the glycoprotein. Binding of HVEM
      requires the formation of an N-terminal hairpin loop of gD; once formed this loop
      masks the nectin-1 binding site on the core of gD. We found that HVEM and nectin
      1 exhibit non-reciprocal competition for binding to gD. The N-terminus of gD does
      not spontaneously form a stable hairpin in the absence of receptor and HVEM does
      not appear to rely on a pre-existing hairpin for binding to gD(3C-38C) mutants.
      However, HVEM function is affected by mutations that impair optimal hairpin
      formation. Furthermore, nectin-1 induces a new conformation of the N-terminus of
      gD. We conclude that the conformation of the N-terminus of gD is actively
      modified by the direct action of both receptors.

PMID- 24314650
TI  - A critical Sp1 element in the rhesus rhadinovirus (RRV) Rta promoter confers high
      level activity that correlates with cellular permissivity for viral replication.
AB  - KSHV establishes characteristic latent infections in vitro, while RRV, a related
      macaque rhadinovirus, establishes characteristic permissive infections with virus
      replication. We identified cells that are not permissive for RRV replication and
      recapitulate the latent KSHV infection and reactivation processes. The RRV
      replication and transactivator (Rta) promoter was characterized in permissive and
      non-permissive cells and compared to the KSHV Rta promoter. Both promoters
      contained a critical Sp1 element, had equivalent activities in different cell
      types, and were inhibited by LANA. RRV and KSHV infections were non-permissive in
      cells with low Rta promoter activity. While RRV infections were permissive in
      cells with high basal promoter activity, KSHV infections remained non-permissive.
      Our studies suggest that RRV lacks the Rta-inducible LANA promoter that is
      responsible for LANA inhibition of the KSHV Rta promoter and induction of latency
      during KSHV infection. Instead, the outcome of RRV infection is determined by
      host factors, such as Sp1.

PMID- 24314651
TI  - miR-24 and miR-205 expression is dependent on HPV onco-protein expression in
      keratinocytes.
AB  - A screen of microRNA (miRNA) expression following differentiation in human
      foreskin keratinocytes (HFKs) identified changes in several miRNAs, including miR
      24 and miR-205. We investigated how expression of Human Papilloma Virus Type-16
      (HPV16) onco-proteins E6 and E7 affected expression of miR-24 and miR-205 during
      proliferation and differentiation of HFKs. We show that the induction of both miR
      24 and miR-205 observed during differentiation of HFKs is lost in HFKs expressing
      E6 and E7. We demonstrate that the effect on miR-205 is due to E7 activity, as
      miR-205 expression is dependent on pRb expression. Finally, we provide evidence
      that miR-24 effects in the cell may be due to targeting of cyclin dependent
      kinase inhibitor p27. In summary, these results indicate that expression of both
      miR-24 and miR-205 are impacted by E6 and/or E7 expression, which may be one
      mechanism by which HPV onco-proteins can disrupt the balance between
      proliferation and differentiation in keratinocytes.

PMID- 24314653
TI  - Alanine scanning mutagenesis of hepatitis C virus E2 cysteine residues: Insights
      into E2 biogenesis and antigenicity.
AB  - Envelope glycoprotein 2 (E2) of hepatitis C virus contains 18 conserved cysteine
      (Cys) residues in its ectodomain. By cysteine-alanine mutagenesis and function
      analysis, six Cys in H77 E2 (C494, C508, C552, C564, C607 and C644) were found to
      be indispensable for recognition by conformation-dependent mAb H53. Removal of
      any of these Cys residues did not affect E2 heterodimerization with E1, but
      notably reduced E1E2 transmembrane transportation. These Cys together with C429
      and C503 were required for conformation-dependent mAb H48 recognition. All of the
      above Cys except C607 were required for H77 and Con1 E2 binding to CD81. None of
      individual mutation of above Cys affected the ability of E2 to induce
      neutralizing antibodies in mice. Mouse antibodies mainly recognize E2 linear
      epitopes and are unrelated to epitopes recognized by human E2 antibodies. The
      findings provide new insights for understanding the biogenesis of functional HCV
      envelope proteins and HCV neutralizing immunity.

PMID- 24314652
TI  - Binding of the rhesus TRIM5alpha PRYSPRY domain to capsid is necessary but not
      sufficient for HIV-1 restriction.
AB  - The PRYSPRY domain of TRIM5alpha provides specificity and the capsid recognition
      motif to retroviral restriction. Restriction of HIV-1 by rhesus TRIM5alpha
      (TRIM5alpharh) has been correlated to its ability to bind to the HIV-1 core,
      suggesting that capsid binding is required for restriction. This work explores
      whether the PRYSPRY domain of TRIM5alpharh exhibits an additional function
      besides binding to the HIV-1 core. Using our recently described structure of the
      PRYSPRY domain, we performed an exhaustive structure-function study of the
      surface and interior residues of the PRYSPRY domain. Testing retroviral
      restriction and capsid binding of an extensive collection of 60 TRIM5alpharh
      PRYSPRY variants revealed that binding is necessary but not sufficient for
      restriction. In support of this hypothesis, we showed that some human tripartite
      motif proteins bind the HIV-1 capsid but do not restrict HIV-1 infection, such as
      human TRIM6 and TRIM34. Overall this work suggested that the PRYSPRY domain
      serves an unknown function, distinct from the binding of TRIM5alpharh to the HIV
      1 core, to block HIV-1 infection.

PMID- 24314654
TI  - The epitope structure of Citrus tristeza virus coat protein mapped by recombinant
      proteins and monoclonal antibodies.
AB  - It has been known that there exists serological differentiation among Citrus
      tristeza virus (CTV) isolates. The present study reports three linear epitopes
      (aa 48-63, 97-104, and 114-125) identified by using bacterially expressed
      truncated coat proteins and ten monoclonal antibodies against the native virions
      of CTV-S4. Site-directed mutagenesis analysis demonstrated that the mutation D98G
      within the newly identified epitope (97)DDDSTGIT(104) abolished its reaction to
      MAbs 1, 4, and 10, and the presence of G98 in HB1-CP also resulted in its failure
      to recognize the three MAbs. Our results suggest that the conformational
      differences in the epitope I (48)LGTQQNAALNRDLFLT(63) between the CPs of isolates
      S4 and HB1 might contribute to the different reactions of two isolates to MAbs 5
      and 6. This study provides new information for the antigenic structures of CTV,
      and will extend the understanding of the processes required for antibody binding
      and aid the development of epitope-based diagnostic tools.

PMID- 24314655
TI  - microRNA expression in hepatitis B virus infected primary treeshrew hepatocytes
      and the independence of intracellular miR-122 level for de novo HBV infection in
      culture.
AB  - Infection of Hepatitis B virus (HBV) in hepatocytes has been known to be
      controlled by multiple cellular factors, while the relationship of the infection
      and liver microRNAs remains obscure. In this study, a miRNA database, containing
      168 unique mature miRNA members from primary hepatocytes of a primate-like
      animal, northern treeshrew (Tupaia belangeri) that is the only species
      susceptible for HBV infection other than human and chimpanzee, was established.
      The relative level of a liver predominant microRNA, miR-122, was markedly
      increased upon HBV infection of the primary tupaia hepatocyte (PTH). However,
      introducing neither miR-122 nor its antagonist anti-miR-122 into PTHs, or, HepG2
      NTCP that is HepG2 cells with the newly identified receptor sodium taurocholate
      cotransporting polypeptide (NTCP) did not alter the viral infection on these
      cells. These data suggest that de novo HBV infection of cultured hepatocytes does
      not depend on the expression level of intracellular miR-122 of the target cells.

PMID- 24314656
TI  - Orsay, Santeuil and Le Blanc viruses primarily infect intestinal cells in
      Caenorhabditis nematodes.
AB  - The discoveries of Orsay, Santeuil and Le Blanc viruses, three viruses infecting
      either Caenorhabditis elegans or its relative Caenorhabditis briggsae, enable the
      study of virus-host interactions using natural pathogens of these two well
      established model organisms. We characterized the tissue tropism of infection in
      Caenorhabditis nematodes by these viruses. Using immunofluorescence assays
      targeting proteins from each of the viruses, and in situ hybridization, we
      demonstrate viral proteins and RNAs localize to intestinal cells in larval stage
      Caenorhabditis nematodes. Viral proteins were detected in one to six of the 20
      intestinal cells present in Caenorhabditis nematodes. In Orsay virus-infected C.
      elegans, viral proteins were detected as early as 6h post-infection. The RNA
      dependent RNA polymerase and capsid proteins of Orsay virus exhibited different
      subcellular localization patterns. Collectively, these observations provide the
      first experimental insights into viral protein expression in any nematode host,
      and broaden our understanding of viral infection in Caenorhabditis nematodes.

PMID- 24314657
TI  - A dsRNA mycovirus, Magnaporthe oryzae chrysovirus 1-B, suppresses vegetative
      growth and development of the rice blast fungus.
AB  - A double-stranded RNA (dsRNA) mycovirus was found in isolate S-0412-II 2a of the
      rice blast fungus Magnaporthe oryzae. Sequence analysis of the five dsRNA
      segments (dsRNA1 through dsRNA5) revealed that this mycovirus is closely related
      to Magnaporthe oryzae chrysovirus 1-A (MoCV1-A), tentatively classified as a
      member of the Chrysoviridae; therefore, it was named Magnaporthe oryzae
      chrysovirus 1-B (MoCV1-B). Virus particles were spherical and composed of the
      ORF1, ORF3 and ORF4 proteins. MoCV1-B-infected isolate S-0412-II 2a showed a more
      severe impaired phenotype than the MoCV1-A-infected isolate. In a virus-cured
      isolate, normal growth was restored, implied that MoCV1-B could be involved in
      this observed phenotype. An unanticipated result was the occurrence of a fungal
      isolate lacking dsRNA5. The nonessential dsRNA5 had higher sequence identity
      (96%) with dsRNA5 of MoCV1-A than with the other dsRNA segments (71-79%),
      indicating that dsRNA5 could be a portable genomic element between MoCV1-A and
      MoCV1-B.

PMID- 24314658
TI  - Exploring the limits of vector construction based on Citrus tristeza virus.
AB  - We examined the limits of manipulation of the Citrus tristeza virus (CTV) genome
      for expressing foreign genes in plants. We previously created a vector with a
      foreign gene cassette inserted between the major and minor coat protein genes,
      which is position 6 from the 3' terminus. Yet, this virus has 10 3'-genes with
      several other potential locations for expression of foreign genes. Since genes
      positioned closer to the 3' terminus tend to be expressed in greater amounts,
      there were opportunities for producing greater amounts of foreign protein. We
      found that the virus tolerated insertions of an extra gene in most positions
      within the 3' region of the genome with substantially increased levels of gene
      product produced throughout citrus trees. CTV was amazingly tolerant to
      manipulation resulting in a suite of stable transient expression vectors, each
      with advantages for specific uses and sizes of foreign genes in citrus trees.

PMID- 24314659
TI  - Gene duplication and phylogeography of North American members of the Hart Park
      serogroup of avian rhabdoviruses.
AB  - Flanders virus (FLAV) and Hart Park virus (HPV) are rhabdoviruses that circulate
      in mosquito-bird cycles in the eastern and western United States, respectively,
      and constitute the only two North American representatives of the Hart Park
      serogroup. Previously, it was suggested that FLAV is unique among the
      rhabdoviruses in that it contains two pseudogenes located between the P and M
      genes, while the cognate sequence for HPV has been lacking. Herein, we
      demonstrate that FLAV and HPV do not contain pseudogenes in this region, but
      encode three small functional proteins designated as U1-U3 that apparently arose
      by gene duplication. To further investigate the U1-U3 region, we conducted the
      first large-scale evolutionary analysis of a member of the Hart Park serogroup by
      analyzing over 100 spatially and temporally distinct FLAV isolates. Our
      phylogeographic analysis demonstrates that although FLAV appears to be slowly
      evolving, phylogenetically divergent lineages co-circulate sympatrically.

PMID- 24314661
TI  - Enhanced IRES activity by the 3'UTR element determines the virulence of FMDV
      isolates.
AB  - A reverse genetics approach was used to identify viral genetic determinants of
      the differential virulence displayed by two field foot-and-mouth disease virus
      (FMDV) strains (A/Arg/00 and A/Arg/01) isolated in Argentina during the 2000-2001
      epidemics. A molecular clone of A/Arg/01 strain and viral chimeras containing the
      S-fragment or the internal ribosome entry site (IRES) of A/Arg/00 in the A/Arg/01
      backbone were constructed and characterized. The IRES appeared as a determining
      factor of the lower level of A/Arg/00 replication in cell culture. High
      throughput RNA probing revealed structural differences between both IRESs.
      Translation experiments using either synthetic viral RNAs (in vitro) or
      bicistronic plasmids (in vivo) showed that these IRESs' activities differ when
      the viral 3' untranslated region (UTR) is present, suggesting that their function
      is differentially modulated by this region. This work provides experimental
      evidence supporting the role of the IRES-3'UTR modulation in determining the
      level of FMDV replication in field strains.

PMID- 24314660
TI  - KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral
      transformation.
AB  - Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly
      expressed during malignancies. We recently documented that Epstein-Barr virus
      (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma
      associated herpesvirus (KSHV) infection induced UCH-L1 expression, via
      cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jkappa and
      activation of the uch-l1 promoter. UCH-L1 expression was also increased in
      Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with
      PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on
      uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products
      expressed in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1
      expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1
      expression. These results indicate that viral latency products of both human
      gamma-herpesviruses contribute to uch-l1 expression, which may contribute to the
      progression of lymphoid malignancies.

PMID- 24314663
TI  - Gig1, a novel antiviral effector involved in fish interferon response.
AB  - Vertebrate interferon (IFN) response defenses against viral infection through the
      induction of hundreds of IFN-stimulated genes (ISGs). Most ISGs are conserved
      across vertebrates; however, little is known about the species-specific ISGs. In
      this study, we reported that grass carp reovirus (GCRV)-induced gene 1 (Gig1),
      previously screened as a virus-induced gene from UV-inactivated GCRV-infected
      crucian carp (Carassius auratus) blastulae embryonic (CAB) cells, was a typical
      fish ISG, which was significantly induced by intracellular poly(I:C) through
      retinoic acid-inducible gene I (RIG-I)-like receptors-triggered IFN signaling
      pathway. Transient or stable overexpression of Gig1 prevented GCRV replication
      efficiently in cultured fish cells. Strikingly, Gig1 homologs were found
      exclusively in fish species forming a novel gene family. These results illustrate
      that there exists a Gig1 gene family unique to fish species and the founding gene
      mediates a novel fish IFN antiviral pathway.

PMID- 24314662
TI  - Methylation of human papillomavirus 16, 18, 31, and 45 L2 and L1 genes and the
      cellular DAPK gene: Considerations for use as biomarkers of the progression of
      cervical neoplasia.
AB  - During progression of cervical cancer, human papillomavirus genomes and cellular
      tumor suppressor genes can become methylated. Toward a better understanding of
      these biomarkers, we studied 104 samples with HPV16, 18, 31, and 45 representing
      five pathological categories from asymptomatic infection to cancer. We grouped
      all samples by HPV type and pathology and measured the overall methylation of
      informative amplicons of HPV late genes and the cellular DAPK gene. Methylation
      of all four HPV types as well as of the DAPK gene is lowest in asymptomatic
      infection and increases successively in all four pathological categories during
      progression to cancer. 27 out of 28 cancer samples showed methylation both in the
      L2/L1 genes as well as in DAPK, but a much lower fraction in all other
      pathological categories. We discuss the problem to develop diagnostic tests based
      on complex methylation patterns that make it difficult to classify amplicons as
      "methylated" or "unmethylated".

PMID- 24314664
TI  - Epstein-Barr virus nuclear antigen 3C interact with p73: Interplay between a
      viral oncoprotein and cellular tumor suppressor.
AB  - The p73 protein has structural and functional homology with the tumor suppressor
      p53, which plays an important role in cell cycle regulation, apoptosis, and DNA
      repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative
      oncogene (DeltaNp73). p73 May play a significant role in p53-deficient lymphomas
      infected with Epstein-Barr virus (EBV). EBV produces an asymptomatic infection in
      the majority of the global population, but it is associated with several human B
      cell malignancies. The EBV-encoded Epstein-Barr virus nuclear antigen 3C (EBNA3C)
      is thought to disrupt the cell cycle checkpoint by interacting directly with p53
      family proteins. Doxorubicin, a commonly used chemotherapeutic agent, induces
      apoptosis through p53 and p73 signaling such that the lowDeltaNp73 level promotes
      the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated
      the mechanism by which EBV infection counters p73alpha-induced apoptosis through
      EBNA3C.

PMID- 24314665
TI  - A short sequence immediately upstream of the internal repeat elements is critical
      for KSHV LANA mediated DNA replication and impacts episome persistence.
AB  - Kaposi's sarcoma-associated herpesvirus LANA (1162 residues) mediates episomal
      persistence of viral genomes during latency. LANA mediates viral DNA replication
      and segregates episomes to daughter nuclei. A 59 residue deletion immediately
      upstream of the internal repeat elements rendered LANA highly deficient for DNA
      replication and modestly deficient for the ability to segregate episomes, while
      smaller deletions did not. The 59 amino acid deletion reduced LANA episome
      persistence by ~14-fold, while sequentially smaller deletions resulted in ~3
      fold, or no deficiency. Three distinct LANA regions reorganized heterochromatin,
      one of which contains the deleted sequence, but the deletion did not abolish
      LANA's ability to alter chromatin. Therefore, this work identifies a short
      internal LANA sequence that is critical for DNA replication, has modest effects
      on episome segregation, and substantially impacts episome persistence; this
      region may exert its effects through an interacting host cell protein(s).

PMID- 24314666
TI  - Human papillomavirus 33 worldwide genetic variation and associated risk of
      cervical cancer.
AB  - Human papillomavirus (HPV) 33, a member of the HPV16-related alpha-9 species
      group, is found in approximately 5% of cervical cancers worldwide. The current
      study aimed to characterize the genetic diversity of HPV33 and to explore the
      association of HPV33 variants with the risk for cervical cancer. Taking advantage
      of the International Agency for Research on Cancer biobank, we sequenced the
      entire E6 and E7 open reading frames of 213 HPV33-positive cervical samples from
      30 countries. We identified 28 HPV33 variants that formed 5 phylogenetic groups:
      the previously identified A1, A2, and B (sub)lineages and the novel A3 and C
      (sub)lineages. The A1 sublineage was strongly over-represented in cervical cases
      compared to controls in both Africa and Europe. In conclusion, we provide a
      classification system for HPV33 variants based on the sequence of E6 and E7 and
      suggest that the association of HPV33 with cervical cancer may differ by variant
      (sub)lineage.

PMID- 24314668
TI  - Comparing PANSS scores and corresponding CGI scores between stable and acute
      schizophrenic patients.

PMID- 24314667
TI  - Specific sequences commonly found in the V3 domain of HIV-1 subtype C isolates
      affect the overall conformation of native Env and induce a neutralization
      resistant phenotype independent of V1/V2 masking.
AB  - Primary HIV-1 isolates are relatively resistant to neutralization by antibodies
      commonly induced after infection or vaccination. This is generally attributed to
      masking of sensitive epitopes by the V1/V2 domain and/or glycans situated at
      various positions in Env. Here we identified a novel masking effect mediated by
      subtype C-specific V3 sequences that contributes to the V1/V2-independent and
      glycan-independent neutralization resistance of chimeric and primary Envs to
      antibodies directed against multiple neutralization domains. Positions at several
      conserved charged and hydrophobic sites in the V3 crown and stem were also shown
      to affect neutralization phenotype. These results indicated that substitutions
      typically present in subtype C and related V3 sequences influence the overall
      conformation of native Env in a way that occludes multiple neutralization targets
      located both within and outside of the V3 domain, and may reflect an alternative
      mechanism for neutralization resistance that is particularly active in subtype C
      and related isolates.

PMID- 24314670
TI  - Rational design, synthesis and antitubercular evaluation of novel 2
      (trifluoromethyl)phenothiazine-[1,2,3]triazole hybrids.
AB  - Molecular hybridization is an emerging structural modification tool to design
      molecules with better pharmacophoric properties. A series of novel 2
      (trifluoromethyl)phenothiazine-1,2,3-triazoles 5a-v designed by hybridizing two
      antitubercular drugs trifluoperazine and I-A09 in a single molecular
      architecture, were synthesized in very good yields using click chemistry. Among
      the all '22' compounds screened for in vitro antimycobacterial activity against
      Mycobacterium tuberculosis H37Rv (Mtb), three analogs 5c, 5l and 5o were found to
      be most potent (MIC: 6.25MUg/mL) antitubercular agents with good selectivity
      index. 

PMID- 24314669
TI  - High-throughput docking for the identification of new influenza A virus
      polymerase inhibitors targeting the PA-PB1 protein-protein interaction.
AB  - A high-throughput molecular docking approach was successfully applied for the
      selection of potential inhibitors of the Influenza RNA-polymerase which act by
      targeting the PA-PB1 protein-protein interaction. Commercially available
      compounds were purchased and biologically evaluated in vitro using an ELISA-based
      assay. As a result, some compounds possessing a 3-cyano-4,6-diphenyl-pyridine
      nucleus emerged as effective inhibitors with the best ones showing IC50 values in
      the micromolar range. 

PMID- 24314671
TI  - Drug discovery considerations in the development of covalent inhibitors.
AB  - In recent years, the number of drug candidates with a covalent mechanism of
      action progressing through clinical trials or being approved by the FDA has
      increased significantly. And as interest in covalent inhibitors has increased,
      the technical challenges for characterizing and optimizing these inhibitors have
      become evident. A number of new tools have been developed to aid this process,
      but these have not gained wide-spread use. This review will highlight a number of
      methods and tools useful for prosecuting covalent inhibitor drug discovery
      programs. 

PMID- 24314672
TI  - A novel indigoid anti-tuberculosis agent.
AB  - The structure of a novel indigoid component was characterized by X-ray
      crystallography. This compound exhibited excellent anti-tuberculosis activity
      against Mycobacterium tuberculosis H37Rv in whole cell culture showing a
      submicromolar minimum inhibitory concentration (MIC). A synthesis of this
      molecule was designed and carried out to produce sufficient material for further
      testing. The in vitro profile, structure, and first synthesis of this indigoid
      component is reported. 

PMID- 24314673
TI  - Cerebral multicystic lesions in a child with L-2 hydroxyglutaric aciduria: a rare
      disease and a rare association.

PMID- 24314674
TI  - Stroke in children with cancer: the tip of the iceberg?

PMID- 24314675
TI  - Solid intraventricular papillary glioneuronal tumor: magnetic resonance imaging
      findings with histopathological correlation.

PMID- 24314676
TI  - Comment on herpes simplex encephalitis with occipital localization in an infant:
      a different route of entry in the brain system?

PMID- 24314677
TI  - Gait impairment and optimizing mobility in multiple sclerosis.
AB  - Multiple sclerosis (MS) is an immune-mediated disease that causes demyelination
      and degeneration within the brain and spinal cord. This may result in many
      impairments, including impaired ambulation, muscle weakness, abnormal tone,
      visual disturbances, decreased sensation, and fatigue. Rehabilitation helps
      patients with MS maximize independence by helping to manage and minimize
      impairments. Deficits seen in ambulation should be addressed to improve energy
      efficiency and reduce falls. Compensation through appropriate prescription of
      assistive devices, bracing, and wheelchairs will help improve safety.
      Rehabilitation can make a significant impact on achieving and maintaining quality
      of life and independence. 

PMID- 24314678
TI  - Spasticity management in multiple sclerosis.
AB  - Spasticity is a prevalent and potentially disabling symptom common in individuals
      with multiple sclerosis. Adequate evaluation and management of spasticity
      requires a careful assessment of the patient's history to determine functional
      impact of spasticity and potential exacerbating factors, and physical examination
      to determine the extent of the condition and culpable muscles. A host of options
      for spasticity management are available: therapeutic exercise, physical
      modalities, complementary/alternative medicine interventions, oral medications,
      chemodenervation, and implantation of an intrathecal baclofen pump. Choice of
      treatment hinges on a combination of the extent of symptoms, patient preference,
      and availability of services. 

PMID- 24314679
TI  - Exercise in multiple sclerosis.
AB  - Exercise is an intervention that may be used in the management of multiple
      sclerosis (MS). Certain exercise physiology characteristics are commonly seen
      among persons with MS, particularly in the more debilitated. Studies have shown
      that properly prescribed exercise programs can improve modifiable impairments in
      MS. Exercise is generally safe and well tolerated. General guidelines are
      available for exercise prescription for the MS population. There are several
      recommendations that may help improve the quality of future MS exercise trials. 

PMID- 24314680
TI  - Caregiving in multiple sclerosis.
AB  - Thirty percent of persons with multiple sclerosis (pwMS) require caregiving owing
      to their disability, and 80% of care to pwMS is provided by informal unpaid
      caregivers. The average caregiver is male, in a spousal/partner relationship with
      the pwMS, and provides more than 4 hours per day of care for many years. The
      physical, emotional, and time-intensive nature of caregiving for pwMS frequently
      impairs the caregiver's own physical and emotional health. Rehabilitation
      medicine professionals should be aware of the high risk of caregiver burden.
      Assessment of caregiver needs and appropriate intervention will help minimize the
      burden on caregivers. 

PMID- 24314681
TI  - Activities of daily living: evaluation and treatment in persons with multiple
      sclerosis.
AB  - Symptoms of multiple sclerosis can create mild to severe changes in a person's
      abilities to perform activities of daily living. Occupational therapy assessment
      and treatment of impairments related to movement, sensory-related symptoms,
      fatigue, and cognitive impairments can have a significant impact on the quality
      of life of persons with multiple sclerosis. 

PMID- 24314682
TI  - Movement disorders in multiple sclerosis.
AB  - Movement disorders constitute a subspecialty of neurology focusing on a variety
      of conditions characterized by hypokinetic, hyperkinetic, or abnormally
      coordinated movements including, among others, tremor, dystonia, parkinsonism,
      myoclonus, chorea, ballismus, tics, restless limbs, and ataxia. The term
      "movement disorders" may be used to refer to either abnormal movements or
      syndromes that cause these abnormal movements. The classification of movement
      disorders is based on phenomenology, individual syndromes, or etiology. This
      article reviews terminology used to describe movement disorders, discusses
      individual movement disorders and their occurrence in patients with multiple
      sclerosis, and reviews treatment options. 

PMID- 24314683
TI  - Multiple sclerosis and fatigue: understanding the patient's needs.
AB  - Fatigue is among the most common and debilitating symptoms of multiple sclerosis
      (MS), affecting approximately 80% of persons who have the disease. Recently, as
      part of the National Institutes of Health Patient Reported Outcome Measurement
      Information System (PROMIS), a bank of items was developed for measuring self
      reported fatigue. This article has two purposes. (1) To assess, from the
      perspective of individuals living with MS, the relevance of a subset of items
      from the PROMIS fatigue item bank. (2) To identify additional aspects of fatigue
      that individuals with MS believe are important for clinicians when asking about
      their fatigue experience. 

PMID- 24314684
TI  - Cognition, cognitive dysfunction, and cognitive rehabilitation in multiple
      sclerosis.
AB  - This article focuses on approaches and techniques for effective cognitive
      rehabilitation with people who have multiple sclerosis (MS). The patterns of
      preserved versus disrupted neuropsychological functions are reviewed. The
      relevant brain anatomy and physiology that underlie the common neurocognitive and
      neurobehavioral changes are described. The essential role is highlighted of
      comprehensive neuropsychological, speech language pathology, and clinical
      evaluations in the design and refinements of cognitive retraining treatment. The
      functional impact of cognitive problems expected with MS is emphasized,
      accompanied by examples of cognitive retraining approaches used to manage them
      and improve day-to-day performance. 

PMID- 24314685
TI  - Bladder management in multiple sclerosis.
AB  - This article reviews the basic principles and therapeutic options in the
      management of the neurogenic bladder due to multiple sclerosis (MS), written
      primarily for the non-urology provider. An algorithm for the initial management
      of the MS patient with lower urinary tract symptoms is provided. 

PMID- 24314686
TI  - Visual issues in multiple sclerosis.
AB  - Multiple sclerosis has several ophthalmic manifestations, including optic
      neuritis, internuclear ophthalmoplegia, and nystagmus. The presentation,
      treatment, and prognosis of visual complaints secondary to multiple sclerosis are
      discussed. Additionally, the use of optical coherence tomography and
      complications related to the use of fingolimod are considered. 

PMID- 24314688
TI  - Evoked potentials in multiple sclerosis.
AB  - Before the development of magnetic resonance imaging (MRI), evoked potentials
      (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem
      auditory evoked responses-were commonly used to determine a second site of
      disease in patients being evaluated for possible multiple sclerosis (MS). The
      identification of an area of the central nervous system showing abnormal
      conduction was used to supplement the abnormal signs identified on the physical
      examination-thus identifying the "multiple" in MS. This article is a brief
      overview of additional ways in which central nervous system (CNS) physiology-as
      measured by EPs-can still contribute value in the management of MS in the era of
      MRIs. 

PMID- 24314694
TI  - Multiple sclerosis rehabilitation.

PMID- 24314689
TI  - Future directions of multiple sclerosis rehabilitation research.
AB  - Multiple sclerosis continues to present a host of rehabilitation challenges,
      specifically the impact of secondary "hidden" conditions on quality of life,
      participation, and employment. To discuss the current state of rehabilitation
      research and direct future research endeavors, a state of the science conference
      was held in November 2010 in Alexandria, Virginia. The conference was presented
      by the University of Washington's Multiple Sclerosis Rehabilitation Research and
      Training Center and focused on the current state of research into secondary
      conditions, outcomes measurement, employment, and the utility of
      psychotherapeutic interventions. This article discusses the details and
      recommendations of this conference. 

PMID- 24314687
TI  - Co-occurring depression and pain in multiple sclerosis.
AB  - Depression and pain are highly prevalent among individuals with multiple
      sclerosis, and they often co-occur. The purpose of this article is to summarize
      the literature and theory related to the comorbidity of pain and depression and
      describe how their presence can impact individuals with multiple sclerosis.
      Additionally, the article discusses how existing treatments of pain and
      depression could be adapted to address shared mechanisms and overcome barriers to
      treatment utilization. 

PMID- 24314695
TI  - Multiple sclerosis rehabilitation.

PMID- 24314696
TI  - Incidence of intraneural needle insertion in ultrasound-guided femoral nerve
      block: a comparison between the out-of-plane versus the in-plane approaches.
AB  - BACKGROUND: The optimal method of ultrasound-guided femoral nerve block (in-plane
      vs. out-of-plane) has not been established. We tested the hypothesis that the
      incidence of needle-nerve contact may be higher with out-of-plane than with in
      plane needle insertion. METHODS: Forty-four patients with hip fracture (American
      Society of Anaesthesiologists physical status I-III) were randomized to receive
      the femoral block with an out-of-plane approach (needle inserted at a 45-60
      degrees  angle 1cm caudal to the midpoint of the ultrasound probe just above the
      femoral nerve) or with an in-plane technique (needle inserted 0.2-0.4 cm from the
      side of the probe lateral to the femoral nerve). Data collected included depth of
      needle insertion, response to nerve electric stimulation, and distribution of the
      injected volume in relation to the nerve (anterior vs. posterior, the latter
      assuming needle-nerve contact). The sensory block onset was tested at 20 min and
      block recovery and any neurologic symptoms were evaluated at 24h. RESULTS: The
      incidence of needle-nerve contact was significantly higher with the out-of-plane
      approach (14/22 patients [64%]) than with the in-plane approach (2/22 patients
      [9%]) (p<0.001) (OR=17.5, 95% CI: 4-79). The rate of paraesthesia on crossing the
      fascia iliaca was similar in the two groups. All blocks uneventfully regressed;
      and no patient developed neurologic symptoms. CONCLUSIONS: Under the conditions
      of our study, needle-nerve contact during femoral nerve block occurs frequently
      with the out-of-plane approach. An in-plane approach results in an equally
      effective femoral block and less incidence of needle-nerve contact.

PMID- 24314697
TI  - Frailty predicts new and persistent depressive symptoms among community-dwelling
      older adults: findings from Singapore longitudinal aging study.
AB  - OBJECTIVE: This study aimed to examine the cross-sectional and longitudinal
      relationships between physical frailty at baseline and depressive symptoms at
      baseline and at follow-up. DESIGN: Four-year prospective study. SETTING:
      Communities in the South East Region of Singapore. PARTICIPANTS: We analyzed data
      of 1827 older Chinese adults aged 55 and above in the Singapore Longitudinal
      Aging Study-I. MEASUREMENTS: The frailty phenotype (based on Fried criteria) was
      determined at baseline, depressive symptoms (Geriatric Depression Scale >= 5) at
      baseline and follow-ups at 2 and 4 years. RESULTS: The mean age of the population
      was 65.9 (standard deviation 7.26). At baseline, 11.4% (n = 209) had depressive
      symptoms, 32.4% (n = 591) were prefrail and 2.5% (n = 46) were frail. In cross
      sectional analysis of baseline data, the adjusted odds ratios (OR)s and 95%
      confidence intervals controlling for demographic, comorbidities, and other
      confounders were 1.69 (1.23-2.33) for prefrailty and 2.36 (1.08-5.15) for
      frailty, (P for linear trend <.001). In longitudinal data analyses, prospective
      associations among all participants were: prefrail: OR = 1.86 (1.08-3.20); frail:
      OR = 3.09 (1.12-8.50); (P for linear trend = .009). Among participants free of
      depressive symptoms at baseline, similar prospective associations were found:
      prefrail OR = 2.26 (1.12-4.57); frail: OR = 3.75 (1.07-13.16); (P for linear
      trend = .009). CONCLUSION: These data support a significant role of frailty as a
      predictor of depression in a relatively younger old Chinese population. Further
      observational and interventional studies should explore short-term dynamic and
      bidirectional associations and the effects of frailty reversal on depression
      risk.

PMID- 24314698
TI  - The measurement of disability in the elderly: a systematic review of self
      reported questionnaires.
AB  - OBJECTIVE: To analyze the contents and formats of general self-reported
      questionnaires on disability that are designed for and/or are widely applied in
      the elderly population to depict a complete picture of this field and help
      researchers to choose proper tools more efficiently. METHODS: A broad systematic
      literature search was performed in September 2013 and included the following
      databases: MEDLINE, EMBASE, CINAHL, PsycINFO, and PROQOLID. The publication
      language was limited to English and Chinese. Two review authors independently
      performed the study selection and data extraction. All of the included
      instruments were extracted and classified using the International Classification
      of Functioning, Disability, and Health framework. RESULTS: Of 5569 articles
      retrieved from the searches and 156 articles retrieved from the pearling, 22
      studies (including 24 questionnaires) fulfilled the inclusion criteria. From
      these, 42 different domains and 458 items were extracted. The most frequently
      used questionnaire was the Barthel Index followed by the Lawton and Brody
      Instrumental Activities of Daily Living Scale and the Katz Index of Activities of
      Daily Living, respectively. The contents and formats of the questionnaires varied
      considerably. Activities and participation were the most commonly assessed
      dimensions. In addition, the Activities of Daily Living, mobility and the
      Instrumental Activities of Daily Living Scale were the most common domains
      assessed among the included questionnaires. CONCLUSIONS: Among the 24 included
      questionnaires, the most frequently used questionnaires were the Barthel Index,
      Lawton and Brody Instrumental Activities of Daily Living Scale, and Katz Index of
      Activities of Daily Living. The content and format of the questionnaires varied
      considerably, but none of the questionnaires covered all essential dimensions of
      the International Classification of Functioning, Disability, and Health
      framework.

PMID- 24314699
TI  - Parkinson disease in long term care facilities: a review of the literature.
AB  - Parkinson disease (PD) is common in long term care (LTC) facilities. The number
      of institutionalized patients with PD will rise sharply in the coming decades
      because of 2 concurrent phenomena: aging of the population leads to an increased
      PD prevalence and improved quality of care has led to a prolonged survival in
      advanced disease stages. Only a few studies have investigated the prevalence and
      clinical characteristics of patients with PD in LTC facilities. Even fewer
      studies have addressed the treatment strategies used to support these
      institutionalized patients, who are mostly in advanced stages of the disease. The
      available evidence suggests that current management of patients with PD in LTC
      facilities is less than optimal. In the Netherlands, and we suspect in many other
      countries, there are no formal guidelines for treating patients with PD who have
      been admitted to a LTC facility. In this review, we describe the epidemiology,
      clinical characteristics, and clinical management of patients with PD in LTC
      settings. We also address potentially modifiable elements of care and provide
      several recommendations to improve the management of PD in these facilities. We
      conclude by suggesting a possible guide for future research in this area. 

PMID- 24314700
TI  - Cardiac and inflammatory biomarkers and in-hospital mortality in older medical
      patients.
AB  - OBJECTIVES: Increasing evidence has mounted in recent years on the potential
      prognostic role of biomarkers out of cardiac-specific medical settings. We aimed
      to test whether cardiac and inflammatory biomarkers are independently associated
      with in-hospital mortality in older unselected medical inpatients undergoing
      standardized multidimensional evaluation. DESIGN: Observational study conducted
      in a metropolitan university-teaching hospital. A standardized, multidimensional
      analysis was carried out on all patients by using medical and hospital discharge
      documentation and interview results integrated with information collected from
      family members or caregivers. PARTICIPANTS AND SETTING: Patients older than 65
      years consecutively admitted to the acute geriatric ward and to 2 acute medical
      wards of the hospital. RESULTS: Male sex; low systolic blood pressure; APACHE
      score; functional impairment in activities of daily living (ADLs), instrumental
      ADLs, and Short Physical Performance Battery (SPPB); cognitive impairment;
      malnutrition; low albumin values; and elevated values of inflammatory and cardiac
      biomarkers were significantly associated with in-hospital mortality at univariate
      analysis. After multivariate analysis, male sex, low systolic blood pressure
      values at entry, severe cognitive impairment, and low functional performance
      measured by the SPPB resulted to be independently associated with in-hospital
      mortality. CONCLUSIONS: The main finding of the present study is that these
      biomarkers, although associated with in-hospital mortality, do not have
      independent predictive significance when a comprehensive and multidimensional
      evaluation is conducted. The main clinical implication is that our findings
      should discourage the indiscriminate recourse to measurement of cardiac and
      inflammatory biomarkers, at least in older medical inpatients, thereby reducing a
      patient's hospital cost and potentially minimizing further unnecessary diagnostic
      procedures.

PMID- 24314701
TI  - One-year stability of care dependency in patients with advanced chronic organ
      failure.
AB  - OBJECTIVES: Care dependency is a determinant of quality of life and survival
      among patients with advanced chronic obstructive pulmonary disease (COPD),
      chronic heart failure (CHF), or chronic renal failure (CRF). The objectives of
      this study were to explore the profiles of care dependency in patients with
      advanced COPD, CHF, or CRF; to study the changes in care dependency during 1-year
      follow-up; and to study whether 1-year changes in care dependency are comparable
      between patients with advanced COPD, CHF, or CRF. DESIGN: Longitudinal
      observational study. PARTICIPANTS: Clinically stable patients with advanced COPD
      (n = 105), CHF (n = 80), or CRF (n = 80) were recruited at outpatient clinics of
      7 Dutch hospitals. MEASUREMENTS: Patients were visited at home at baseline, and
      at 4, 8, and 12 months to assess demographic and clinical characteristics,
      comorbidities (Charlson comorbidity index), care dependency (Care Dependency
      Scale), mobility, health status, and symptom burden. RESULTS: COPD and CHF
      patients reported a higher baseline level of care dependency than patients with
      CRF. Care dependency differed between patients with COPD, CHF, or CRF in the
      items 'getting (un)dressed,' 'hygiene,' 'contact with others,' and 'sense of
      rules/values.' One-year follow-up was completed by 206 patients (77.7%). Patients
      with COPD were more likely to experience an increase in care dependency. An
      increase in care dependency was associated with higher age, higher number of
      hospital admissions, decrease in health status, and worsening of Charlson
      comorbidity index score. CONCLUSIONS: Care dependency profiles differ between
      patients with COPD, CHF, or CRF. Patients with advanced COPD are at risk for a 1
      year increase in care dependency. Regular assessment of care dependency and
      addressing care dependency in palliative care programs for patients with advanced
      COPD, CHF, or CRF are needed.

PMID- 24314702
TI  - [What if living on a farm protected against lung cancer, too?].

PMID- 24314703
TI  - [Illustrated interpretation of cardio-pulmonary exercise testing].

PMID- 24314704
TI  - [French recommendations for idiopathic pulmonary fibrosis: Oriented toward
      practice].

PMID- 24314705
TI  - [Introduction to the thematic series: "Sleep"].

PMID- 24314706
TI  - [Ventilator modes and settings during non-invasive ventilation: effects on
      respiratory events and implications for their identification. 2011].
AB  - Compared with invasive ventilation, non-invasive ventilation (NIV) has two unique
      characteristics: its non-hermetic nature and the fact that the ventilator-lung
      assembly cannot be considered as a single-compartment model because of the
      presence of variable resistance represented by the upper airways. When NIV is
      initiated, the ventilator settings are determined empirically based on clinical
      evaluation and blood gas variations. However, NIV is predominantly applied during
      sleep. Consequently, to assess overnight patient-machine "agreement" and efficacy
      of ventilation, more specific and sophisticated monitoring is needed. The
      effectiveness of NIV might therefore be more correctly assessed by sleep studies
      than by daytime assessment. The simplest monitoring can be done from flow and
      pressure curves from the mask or the ventilator circuit. Examination of these
      tracings can give useful information to evaluate if the settings chosen by the
      operator were the right ones for that patient. However, as NIV allows a large
      range of ventilatory parameters and settings, it is mandatory to have information
      about this to better understand patient-ventilator interaction. Ventilatory
      modality, mode of triggering, pressurization slope, use or not of positive end
      expiratory pressure and type of exhalation as well as ventilator performances may
      all have physiological consequences. Leaks and upper airway resistance variations
      may, in turn, modify these patterns. This article discusses the equipment
      available for NIV, analyses the effect of different ventilator modes and settings
      and of exhalation and connecting circuits on ventilatory traces and gives the
      background necessary to understand their impact on nocturnal monitoring of NIV. 

PMID- 24314707
TI  - [Inhalation therapy: inhaled generics, inhaled antidotes, the future of anti
      infectives and the indications of inhaled pentamidine. GAT aerosolstorming, Paris
      2012].
AB  - The working group on aerosol therapy (GAT) of the Societe de pneumologie de
      langue francaise (SPLF) organized its third "Aerosolstorming" in 2012. During the
      course of one day, different aspects of inhaled therapy were discussed, and these
      will be treated separately in two articles, this one being the first. Inhaled
      products represent a large volume of prescriptions both in the community and in
      hospital settings and they involve various specialties particularly ENT and
      respiratory care. Technical aspects of the development of these products, their
      mode of administration and compliance with their indications are key elements for
      the effective therapeutic use of inhaled treatments. In this first article, we
      will review issues concerning generic inhaled products, the existence of inhaled
      antidotes, new anti-infective agents and indications for inhaled pentamidine. 

PMID- 24314708
TI  - [Sleep: regulation and phenomenology].
AB  - This article describes the two-process model of sleep regulation. The 24-hour
      sleep-wake cycle is regulated by a homeostatic process and an endogenous, 2
      oscillators, circadian process, under the influence of external synchronisers.
      These two processes are partially independent but influence each other, as shown
      in the two-sleep-process auto-regulation model. A reciprocal inhibition model of
      two interconnected neuronal groups, "SP on" and "SP off", explains the regular
      recurrence of paradoxical sleep. Sleep studies have primarily depended on
      observation of the subject and have determined the optimal conditions for sleep
      (position, external conditions, sleep duration and need) and have studied the
      consequences of sleep deprivation or modifications of sleep schedules. Then,
      electrophysiological recordings permitted the classification of sleep stages
      according to the observed EEG patterns. The course of a night's sleep is reported
      on a "hypnogram". The adult subject falls asleep in non-REM sleep (N1), then
      sleep deepens progressively to stages N2 and N3 with the appearance of spindles
      and slow waves (N2). Slow waves become more numerous in stage N3. Every 90minutes
      REM sleep recurs, with muscle atonia and rapid eye movements. These adult sleep
      patterns develop progressively during the 2 first years of life as total sleep
      duration decreases, with the reduction of diurnal sleep and of REM sleep. Around
      2 to 4 months, spindles and K complexes appear on the EEG, with the
      differentiation of light and deep sleep with, however, a predominance of slow
      wave sleep. 

PMID- 24314709
TI  - [Cardiopulmonary exercise testing and unexpected dyspnea].
AB  - Cardiopulmonary exercise testing (CPET) is the examination of choice to
      understand mechanisms responsible for dyspnea in patients without significant
      medical history. The three observations illustrate the major interest of the CPET
      in this frequent situation in clinical practice. A 68-year-old man who has severe
      dyspnea in her leisure time hiking in the mountains, a 25-year cyclist presenting
      disabling dyspnea follow competitors racing neo-professional cyclists, and a 37
      year woman who developed a persistent dyspnea, 6 months after delivery. In these
      three situations, CPET determined the disorder responsible for the symptoms
      without increasing the diagnostic tests. 

PMID- 24314710
TI  - [Cypress pollen allergy].
AB  - Cypress belongs to the Cupressaceae family, which includes 140 species with non
      deciduous foliage. The most important genera in allergic diseases are Cupressus
      sempervirens or Green cypress, Cupressus arizonica or Blue cypress, Juniperus
      oxycedrus, Juniperus communis and Thuya. Because J. oxycedrus pollinates in
      October, C. sempervirens in January and February, C. arizonica in February and
      March, J. communis in April, the symptomatic period is long-lasting. Because of
      global warming, the pollination period is tending to last longer and Cupressaceae
      species are becoming established further the north. In Mediterranean countries,
      cypress is by far the most important pollinating species, accounting for half of
      the total pollination. The major allergens belong to group 1. The other allergens
      from cypress and Juniper share 75 to 97 % structural homology with group 1 major
      allergens. The prevalence of cypress allergy in the general population ranges
      from 5 % to 13 %, according to exposure to the pollen. Among outpatients
      consulting an allergist, between 9 and 35 %, according to different studies, are
      sensitized to cypress pollen. Repeated cross-sectional studies performed at
      different time intervals have demonstrated a threefold increase in the percentage
      of cypress allergy. Risk factors include a genetic predisposition and/or a strong
      exposure to pollen, but air pollutants could play a synergistic role. The study
      of the natural history of cypress allergy allows the identification of a subgroup
      of patients who have no personal or family history of atopy, whose disease began
      later in life, with low total IgE and often monosensitization to cypress pollen.
      In these patients, the disease is allergic than rather atopic. In the clinical
      picture, rhinitis is the most prevalent symptom but conjunctivitis the most
      disabling. A cross-reactivity between cypress and peach allergy has been
      demonstrated. The pharmacological treatment of cypress allergy is not different
      from that for other allergies. Hyposensitization has been used, at first by
      injection, but nowadays mostly through the sublingual route, but clinical trials
      have included few patients. Avoidance can be implemented at the individual level
      but also at the community levels using alternative plants, low-pollinating
      cypresses or by trimming hedges prior to pollination. 

PMID- 24314711
TI  - [French practical guidelines for the diagnosis and management of idiopathic
      pulmonary fibrosis. From the National Reference and the Competence centers for
      rare diseases and the Societe de Pneumologie de Langue Francaise].

PMID- 24314712
TI  - [Recommendations for pediatric oxygen therapy in acute and chronic settings:
      Needs assessment, implementation criteria, prescription practices and follow-up].
AB  - Recommendations for acute and long-term oxygen therapy (needs assessment,
      implementation criteria, prescription practices, and follow-up) in children were
      produced by the Groupe de Recherche sur les Avancees en Pneumo-Pediatrie (GRAPP)
      under the auspices of the French Paediatric Pulmonology and Allergology Society
      (SP2A). The Haute Autorite de Sante (HAS) methodology, based on the Formalized
      Consensus, was used. A first panel of experts analyzed the English and French
      literature to provide a second panel of experts with recommendations to validate.
      Only the recommendations are presented here, but the full text
      (arguments+recommendations) is available at the website of the French Paediatric
      Society: www.sfpediatrie.com. 

PMID- 24314713
TI  - ABO blood group discrepancies among blood donors in Regional Blood Transfusion
      Centre GTB Hospital, Delhi, India.
AB  - BACKGROUND: Regional Blood Transfusion Centre (RBTC), GTB Hospital, Delhi is
      providing safe and quality blood to one third of Delhi population. A discrepancy
      exists when reactions in forward grouping do not match with reverse grouping or
      if the previous and current results do not match. AIM: To analyze ABO blood group
      discrepancies in an algorithmic manner, and to access the incidence and causes of
      ABO discrepancies among blood donors. MATERIAL AND METHODS: Retrospective data of
      blood donors with blood group discrepancies was recorded in Regional Blood
      Transfusion Centre (East) Delhi, during a period of 3years from January 2010 to
      May 2013. DiaMed-ID Card Micro Typing System using Gel Cards (Cressier sur Morat,
      Switzerland) were used for determination of the ABO/Rh blood groups combined with
      reverse grouping. A detailed serological workup of these cases was studied for
      recognition and resolution of the blood group discrepancy. RESULTS: Total number
      of donors during the study period were 104,010 (30,120; 31,117; 32,173 and 10,600
      respectively). Blood group discrepancies were found in 51 cases (0.04%). There
      were 30 (58.8%) cases with low avidity anti-B Antibodies, 10 (19.6%) cases with
      weaker expression or subgroups of A, 2 (3.9%) cases with weaker expression or
      subgroups of B, 5(9.8%) cases with unexpected alloantibodies (Anti-N and Anti-M,
      Anti-Lea) and one(1.9%) case of Bombay blood group. In 3 cases, discrepancy could
      not be resolved and were referred to reference laboratory for confirmation by
      molecular analysis. The most frequent cause of discrepancy in forward grouping
      was found to be weak A or B antigen expressions and in reverse grouping decreased
      anti-B titers was most common. CONCLUSION: All discrepancies reported on ABO cell
      and serum grouping must be investigated further, so that correct blood group is
      reported, minimizing the chances of transfusion reaction. A note of caution
      should be mentioned on the blood group card to prevent ABO incompatibility in
      case of transfusion.

PMID- 24314714
TI  - Psychometric properties of the Barratt Impulsiveness Scale in patients with
      gambling disorders, hypersexuality, and methamphetamine dependence.
AB  - Although the Barratt Impulsiveness Scale (BIS; Patton, Stanford, & Barratt, 1995)
      is a widely-used self-report measure of impulsivity, there have been numerous
      questions about the invariance of the factor structure across clinical
      populations (Haden & Shiva, 2008, 2009; Ireland & Archer, 2008). The goal of this
      article is to examine the factor structure of the BIS among a sample consisting
      of three populations exhibiting addictive behaviors and impulsivity: pathological
      gamblers, hypersexual patients, and individuals seeking treatment for
      methamphetamine dependence to determine if modification to the existing factors
      might improve the psychometric properties of the BIS. The current study found
      that the factor structure of the BIS does not replicate in this sample and
      instead produces a 12-item three-factor solution consisting of motor
      impulsiveness (5 items), non-planning impulsiveness (3 items), and immediacy
      impulsiveness (4 items). The clinical utility of the BIS in this population is
      questionable. The authors suggest future studies to investigate comparisons with
      this modified version of the BIS and other impulsivity scales such as the UPPS-P
      Impulsive Behavior Scale in clinical populations when assessing disposition
      toward rash action. 

PMID- 24314715
TI  - Protective efficacy of a live attenuated Mycoplasma hyopneumoniae vaccine with an
      ISCOM-matrix adjuvant in pigs.
AB  - An attenuated Mycoplasma hyopneumoniae vaccine that requires intrathoracic
      administration is commercially available for use against mycoplasmal pneumonia in
      China. Given the limitations of such a route of administration, this study was
      undertaken to assess the capacity of an ISCOM-matrix adjuvant to enhance
      immunogenicity following intramuscular use. Immune responses in pigs following
      vaccination and subsequent intra-tracheal bacterial inoculation were examined
      using lymphocyte proliferation, serology and mucosal IgA in both nasal and saliva
      swabs. Vaccination induced clear lymphocyte proliferation, but only slight serum
      antibody responses although these were significantly increased following
      experimental infection. Mucosal IgA was not detected in either nasal or salivary
      secretions. Following bacterial challenge, animals vaccinated with the adjuvant
      containing live vaccine exhibited less severe pulmonary lesions (median score
      3.67) than unvaccinated pigs (median score 13.58). The degree of ciliary loss on
      the respiratory tract surface was reduced in vaccinated pigs compared with
      experimentally infected controls. The findings indicated that the adjuvant
      vaccine administered IM provided protection against experimentally induced
      mycoplasmal pneumonia and could have commercial potential. 

PMID- 24314716
TI  - Stride to stride variability in joint angle profiles during transitions from trot
      to canter in horses.
AB  - Spontaneous transitions from anti-phase to in-phase manual coordination are
      explained in the Haken model that describes the two preferred states as stable
      regions that work as attractors in a stability landscape. Switching between
      states coincides with a temporary loss of stability. Coordination variability is
      believed to be indicative of such a loss of stability. In this study, the
      hypothesis was tested that an increase in variability in the angle profiles of
      the joints responsible for the transition will precede the transition. A full
      gait analysis of four miniature horses transitioning from trot to canter was
      performed. Joint angle profiles were determined for the joints of all four limbs
      and were time-normalised to stride duration. Per horse and per stride, the
      coefficient of variance was calculated as the mean standard deviation of the
      joint profile over all trials divided by the mean joint angle * 100. As
      hypothesised, the most proximal limb joints (hip, scapulothoracic, shoulder)
      followed the predictions to a large extent. The variability of the hip joint
      angle of the trailing hind limb showed a peak of variability at stride 0; this
      was quickly reduced after the transition was completed. The detection of this
      brief perturbation in the hip joint indicates the importance of this joint in the
      transition process. The hip joint is related to the movements of the limb, pelvis
      and back, which is one of the main differences between symmetrical and
      asymmetrical gaits. 

PMID- 24314717
TI  - Elastin content is high in the canine cruciate ligament and is associated with
      degeneration.
AB  - Cruciate ligaments (CLs) are primary stabilisers of the knee joint and canine
      cranial cruciate ligament disease (CCLD) and rupture is a common injury. Elastin
      fibres, composed of an elastin core and fibrillin containing microfibrils, are
      traditionally considered minor components of the ligament extracellular matrix
      (ECM). However, their content and distribution in CLs is unknown. The purposes of
      this study were to determine the elastin content of canine CLs and to ascertain
      its relationship to other biochemical components and histological architecture.
      Macroscopically normal CLs were harvested from Greyhounds (n=11), a breed with a
      low risk of CCLD. Elastin, collagen and sulfated glycosaminoglycan content were
      measured and histological scoring systems were developed to quantify ECM changes
      using a modified Vasseur score (mVS) and oxytalan fibre (bundles of microfibrils)
      staining. Elastin contents were 9.86 +/- 3.97% dry weight in the cranial CL and
      10.79 +/- 4.37% in the caudal CL, respectively, and did not alter with advancing
      histological degeneration. All CLs demonstrated mild degenerative changes, with
      an average mVS score of 11.9 +/- 3.3 (maximum 24). Increasing degeneration of the
      ligament ECM showed a positive correlation (r=0.690, P<0.001) with increased
      oxytalan fibre staining within the ECM. Elastin is an abundant protein in CLs
      forming a greater proportion of the ligament ECM than previously reported. The
      appearance of oxytalan fibres in degenerative CL ECM may reflect an adaptive or
      reparative response to normal or increased loads. This finding is important for
      future therapeutic or ligament replacement strategies associated with cranial CL
      injury.

PMID- 24314718
TI  - An association between benzodiazepine use and occurrence of benign brain tumors.
AB  - OBJECTIVE: This study was designed to evaluate the impact of long-term
      benzodiazepine use on the subsequent risk of benign brain tumor (BBT) or
      malignant brain tumor (MBT) development. METHOD: We used data from the National
      Health Insurance System of Taiwan. For the study cohort, we identified 62,186
      patients who had been prescribed benzodiazepine for at least 2 months between
      January 1, 2000 and December, 31, 2009. For each of the benzodiazepine cases, we
      randomly selected one insured person from the non-benzodiazepine cohort with
      frequency matching sex, age, and year of index date. The non-benzodiazepine
      cohort comprised 62,050 patients. The related hazard ratios (HRs) and 95%
      confidence intervals (CIs) of developing brain tumors were investigated. RESULTS:
      The overall BBT incidence rate was 3.33-fold higher in the benzodiazepine cohort
      than the non-benzodiazepine cohort (46.3 vs 13.9 per 100,000 person-years) with
      an adjusted HR of 3.15 (95% CI=2.37-4.20). Similarly, the MBT incidence rate was
      84% higher in the benzodiazepine cohort (3.71 vs 2.02 per 1000 person-years), and
      the adjusted HR of 1.21 (95% CI=0.52-2.81) was not statistically significant.
      When compared with the non-benzodiazepine cohort, the adjusted HRs of BBTs
      increased with benzodiazepine dosage (adjusted HR=2.12, 95% CI=1.45-3.10, for 36
      150 mg/year; adjusted HR=7.03, 95% CI=5.19-9.51, for >=151 mg/year). CONCLUSION:
      In this population-based study, we found a significant increase in the risk of
      benign brain tumor development in a cohort of long-term BZD users.

PMID- 24314719
TI  - Longitudinal changes in brain volumes and cerebrovascular lesions on MRI in
      patients with manifest arterial disease: the SMART-MR study.
AB  - We estimated the progression of brain atrophy and cerebrovascular lesions on MRI
      in a prospective cohort of patients with various manifestations of arterial
      disease. Within the SMART-MR study, using brain MRI data from baseline and after
      on average 3.9 years of follow-up, intracranial volume (ICV), total brain,
      cortical gray matter, ventricular, white matter lesion volumes and visually rated
      infarcts were obtained from 663 patients (mean age 57 +/- 9 years, 81% men).
      Global and cortical atrophy increased quadratically with age. Men showed more
      progression of global and cortical atrophy than women (mean difference in change
      (95% CI): -0.25 (-0.44; -0.06) and -0.94 (-1.35; -0.52)% ICV) and had an
      increased risk of new brain infarcts (OR = 2.7, 95% CI 1.2-6.1). Compared with
      coronary artery disease patients, cerebrovascular disease patients showed more
      progression of cortical and subcortical atrophy and an increased risk of new
      brain infarcts, and peripheral arterial disease patients showed more progression
      of cortical atrophy. These results were independent of cerebrovascular lesions
      and cardiovascular risk factors. In patients with manifest arterial disease,
      brain atrophy tended to accelerate with older age and men had more progression of
      brain atrophy and cerebrovascular lesions than women. Additionally, patients with
      cerebrovascular and peripheral arterial disease showed the most prominent
      progression of atrophy and lesions.

PMID- 24314720
TI  - Neuroprotective effects of Nigella sativa extract on cell death in hippocampal
      neurons following experimental global cerebral ischemia-reperfusion injury in
      rats.
AB  - BACKGROUND: Global cerebral ischemia followed by reperfusion, leads to extensive
      neuronal damage, particularly the neurons in the hippocampal CA region. Recent
      studies have demonstrated that pharmacological agents, such as Nigella sativa L.
      (Ranunculaceae) that is an annual herbaceous flowering plant, given at the time
      of reperfusion afforded protection against ischemia, which is referred to as
      pharmacological post conditioning. OBJECTIVES: The aim of this study was to
      evaluate the neuroprotective effects of Nigella sativa in the hippocampus neurons
      of rats exposed to global ischemia/reperfusion. METHODS: In the present study 30
      Wister rats (200-250 g) were divided into 5 groups namely sham (operated without
      treatment), control (operation with normal saline treatment), and 3 treatment
      groups with Nigella sativa 1mg/kg, 10mg/kg and 50mg/kg. Firstly, the animals were
      anesthetized by ketamin and xylazine, and then the right carotid artery was
      operated upon dissection of the soft tissues around it and ligation by a clamp
      for 20 min. The Nigella sativa extraction was used during surgery through IP
      route and after 72 h the animals were euthanized and their brain removed, fixed
      and prepared for histopathological examinations. RESULTS: In treatment group
      (1mg/kg) the interstitial neuron frequency which contains cytoplasmic edema,
      along with CA, was 28 cells, whereas the edematous astrocyte number along with CA
      in this group was 115 cells. In the treatment group (10mg/kg) the interstitial
      neurons of cornua ammonis (CA) were 15 and the edematous astrocytes were 122
      cells and in the treatment group (50mg/kg) the number of edematous interstitial
      neurons was 7 cells in distance of 2900 MU of CA. In such group the number of
      edematous interstitial neurons was less as well. In this group the appearance of
      CA cells was more similar to control group, not only the edema decreased in
      interstitial and astrocyte cells, but it dramatically decreased in pyramidal
      cells. Our study revealed that the Nigella sativa extraction could prevent
      intracellular edema of interneurons in 50mg/kg group significantly compared to
      sham group (91.6%) and the extraction (50mg/kg) decreased edematous astrocytes
      67.1% dramatically compared to sham group. Furthermore there was no significant
      difference between control and two treatment groups (1 and 10mg/kg) (P>0.05),
      CONCLUSION: Our finding suggested that the N. sativa extraction could prevent the
      cerebral edema which the best result was obtained in 50mg/kg group; consequently
      such extraction is able to prevent ischemia/reperfusion in the hippocampus tissue
      of the brain.

PMID- 24314721
TI  - Cortical projection neurons: sprung from the same root.
AB  - Whether cortical projection neurons (CPNs) are generated by multipotent or fate
      restricted progenitors is not completely understood. In this issue of Neuron, Guo
      et al. (2013) provide evidence that mouse Fezf2-expressing radial glial cells are
      multipotent progenitors that sequentially generate all major CPN subtypes and
      glia. 

PMID- 24314722
TI  - Division of labor for division: inhibitory interneurons with different spatial
      landscapes in the olfactory system.
AB  - Normalizing neural responses by the sum of population activity allows the nervous
      system to adjust its sensitivity according to task demands, facilitating
      intensity-invariant information processing. In this issue of Neuron, two studies,
      Kato et al. (2013) and Miyamichi et al. (2013), suggest that parvalbumin-positive
      interneurons in the olfactory bulb play a role in this process. 

PMID- 24314723
TI  - A surprised amygdala looks to the cortex for meaning.
AB  - Learning models propose a role for both signed and unsigned prediction errors in
      updating associations between cues and aversive outcomes. In this issue of
      Neuron, Klavir et al. (2013) show how these errors arise from the interplay
      between the amygdala and anterior cingulate cortex. 

PMID- 24314724
TI  - EEG and MEG: relevance to neuroscience.
AB  - To understand dynamic cognitive processes, the high time resolution of EEG/MEG is
      invaluable. EEG/MEG signals can play an important role in providing measures of
      functional and effective connectivity in the brain. After a brief description of
      the foundations and basic methodological aspects of EEG/MEG signals, the
      relevance of the signals to obtain novel insights into the neuronal mechanisms
      underlying cognitive processes is surveyed, with emphasis on neuronal
      oscillations (ultra-slow, theta, alpha, beta, gamma, and HFOs) and combinations
      of oscillations. Three main functional roles of brain oscillations are put in
      evidence: (1) coding specific information, (2) setting and modulating brain
      attentional states, and (3) assuring the communication between neuronal
      populations such that specific dynamic workspaces may be created. The latter form
      the material core of cognitive functions. 

PMID- 24314725
TI  - A role for correlated spontaneous activity in the assembly of neural circuits.
AB  - Before the onset of sensory transduction, developing neural circuits
      spontaneously generate correlated activity in distinct spatial and temporal
      patterns. During this period of patterned activity, sensory maps develop and
      initial coarse connections are refined, which are critical steps in the
      establishment of adult neural circuits. Over the last decade, there has been
      substantial evidence that altering the pattern of spontaneous activity disrupts
      refinement, but the mechanistic understanding of this process remains incomplete.
      In this review, we discuss recent experimental and theoretical progress toward
      the process of activity-dependent refinement, focusing on circuits in the visual,
      auditory, and motor systems. Although many outstanding questions remain, the
      combination of several novel approaches has brought us closer to a comprehensive
      understanding of how complex neural circuits are established by patterned
      spontaneous activity during development. 

PMID- 24314726
TI  - A modular gain-of-function approach to generate cortical interneuron subtypes
      from ES cells.
AB  - Whereas past work indicates that cortical interneurons (cINs) can be generically
      produced from stem cells, generating large numbers of specific subtypes of this
      population has remained elusive. This reflects an information gap in our
      understanding of the transcriptional programs required for different interneuron
      subtypes. Here, we have utilized the directed differentiation of stem cells into
      specific subpopulations of cortical interneurons as a means to identify some of
      these missing factors. To establish this approach, we utilized two factors known
      to be required for the generation of cINs, Nkx2-1 and Dlx2. As predicted, their
      regulated transient expression greatly improved the differentiation efficiency
      and specificity over baseline. We extended upon this "cIN-primed" model in order
      to establish a modular system whereby a third transcription factor could be
      systematically introduced. Using this approach, we identified Lmo3 and Pou3f4 as
      genes that can augment the differentiation and/or subtype specificity of cINs in
      vitro. 

PMID- 24314727
TI  - Sensory experience shapes the development of the visual system's first synapse.
AB  - Specific connectivity patterns among neurons create the basic architecture
      underlying parallel processing in our nervous system. Here we focus on the visual
      system's first synapse to examine the structural and functional consequences of
      sensory deprivation on the establishment of parallel circuits. Dark rearing
      reduces synaptic strength between cones and cone bipolar cells, a previously
      unappreciated effect of sensory deprivation. In contrast, rod bipolar cells,
      which utilize the same glutamate receptor to contact rods, are unaffected by dark
      rearing. Underlying the physiological changes, we find the localization of
      metabotropic glutamate receptors within cone bipolar, but not rod bipolar, cell
      dendrites is a light-dependent process. Furthermore, although cone bipolar cells
      share common cone partners, each bipolar cell type that we examined depends
      differentially on sensory input to achieve mature connectivity. Thus, visual
      experience differentially affects maturation of rod versus cone pathways and of
      cell types within the cone pathway. 

PMID- 24314728
TI  - Fezf2 expression identifies a multipotent progenitor for neocortical projection
      neurons, astrocytes, and oligodendrocytes.
AB  - Progenitor cells in the cerebral cortex sequentially generate distinct classes of
      projection neurons. Recent work suggests the cortex may contain intrinsically
      fate-restricted progenitors marked by expression of Cux2. However, the
      heterogeneity of the neocortical ventricular zone as well as the contribution of
      lineage-restricted progenitors to the overall cortical neurogenic program remains
      unclear. Here, we utilize in vivo genetic fate mapping to demonstrate that Fezf2
      expressing radial glial cells (RGCs) exist throughout cortical development and
      sequentially generate all major projection neuron subtypes and glia. Moreover, we
      show that the vast majority of CUX2+ cells in the VZ and SVZ are migrating
      interneurons derived from the subcortical telencephalon. Examination of the
      embryonic cortical progenitor population demonstrates that Cux2+ RGCs generate
      both deep- and upper-layer projection neurons. These results identify Fezf2+
      radial glial cells as a multipotent neocortical progenitor and suggest that the
      existence, and molecular identity, of laminar-fate-restricted RGCs awaits further
      investigation.

PMID- 24314729
TI  - A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster
      controls rival-induced prolonged mating.
AB  - A primary function of males for many species involves mating with females for
      reproduction. Drosophila melanogaster males respond to the presence of other
      males by prolonging mating duration to increase the chance of passing on their
      genes. To understand the basis of such complex behaviors, we examine the genetic
      network and neural circuits that regulate rival-induced Longer-Mating-Duration
      (LMD). Here, we identify a small subset of clock neurons in the male brain that
      regulate LMD via neuropeptide signaling. LMD requires the function of pigment
      dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd
      neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two
      neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s
      LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal
      activities of a subset of clock neurons involved in neuropeptide signaling for
      LMD. 

PMID- 24314730
TI  - A tale of two retinal domains: near-optimal sampling of achromatic contrasts in
      natural scenes through asymmetric photoreceptor distribution.
AB  - For efficient coding, sensory systems need to adapt to the distribution of
      signals to which they are exposed. In vision, natural scenes above and below the
      horizon differ in the distribution of chromatic and achromatic features.
      Consequently, many species differentially sample light in the sky and on the
      ground using an asymmetric retinal arrangement of short- (S, "blue") and medium-
      (M, "green") wavelength-sensitive photoreceptor types. Here, we show that in mice
      this photoreceptor arrangement provides for near-optimal sampling of natural
      achromatic contrasts. Two-photon population imaging of light-driven calcium
      signals in the synaptic terminals of cone-photoreceptors expressing a calcium
      biosensor revealed that S, but not M cones, preferred dark over bright stimuli,
      in agreement with the predominance of dark contrasts in the sky but not on the
      ground. Therefore, the different cone types do not only form the basis of "color
      vision," but in addition represent distinct (achromatic) contrast-selective
      channels.

PMID- 24314732
TI  - Functional connectivity between amygdala and cingulate cortex for adaptive
      aversive learning.
AB  - The ability to switch flexibly between aversive and neutral behaviors based on
      predictive cues relies on learning driven by surprise or errors in outcome
      prediction. Surprise can occur as absolute value of the error (unsigned error) or
      its direction (signed errors; positive when something unexpected is delivered and
      negative when something expected is omitted). Signed and unsigned errors coexist
      in the brain and were associated with different systems, but how they interact
      and form across large networks remains vague. We recorded simultaneously in the
      amygdala and dorsal anterior cingulate cortex (dACC) of monkeys performing a
      reversal aversive-conditioning paradigm and quantified changes in interregional
      correlations when contingencies shift. We report that errors exist in different
      magnitudes and that they differentially develop at millisecond resolution. Our
      results support a model where unsigned errors first develop in the amygdala
      during successful learning and then propagate into the dACC, where signed errors
      develop and are distributed back to the amygdala. 

PMID- 24314731
TI  - Inhibition-induced theta resonance in cortical circuits.
AB  - Both circuit and single-cell properties contribute to network rhythms. In vitro,
      pyramidal cells exhibit theta-band membrane potential (subthreshold) resonance,
      but whether and how subthreshold resonance translates into spiking resonance in
      freely behaving animals is unknown. Here, we used optogenetic activation to
      trigger spiking in pyramidal cells or parvalbumin immunoreactive interneurons
      (PV) in the hippocampus and neocortex of freely behaving rodents. Individual
      directly activated pyramidal cells exhibited narrow-band spiking centered on a
      wide range of frequencies. In contrast, PV photoactivation indirectly induced
      theta-band-limited, excess postinhibitory spiking in pyramidal cells (resonance).
      PV-inhibited pyramidal cells and interneurons spiked at PV-inhibition troughs,
      similar to CA1 cells during spontaneous theta oscillations. Pharmacological
      blockade of hyperpolarization-activated (I(h)) currents abolished theta
      resonance. Inhibition-induced theta-band spiking was replicated in a pyramidal
      cell-interneuron model that included I(h). Thus, PV interneurons mediate
      pyramidal cell spiking resonance in intact cortical networks, favoring
      transmission at theta frequency.

PMID- 24314733
TI  - Neuronal origins of choice variability in economic decisions.
AB  - To investigate the mechanisms through which economic decisions are formed, I
      examined the activity of neurons in the orbitofrontal cortex while monkeys chose
      between different juice types. Different classes of cells encoded the value of
      individual offers (offer value), the value of the chosen option (chosen value),
      or the identity of the chosen juice (chosen juice). Choice variability was partly
      explained by the tendency to repeat choices (choice hysteresis). Surprisingly,
      near-indifference decisions did not reflect fluctuations in the activity of offer
      value cells. In contrast, near-indifference decisions correlated with
      fluctuations in the preoffer activity of chosen juice cells. After the offer, the
      activity of chosen juice cells reflected the decision difficulty but did not
      resemble a race-to-threshold. Finally, chosen value cells presented an "activity
      overshooting" closely related to the decision difficulty and possibly due to
      fluctuations in the relative value of the juices. This overshooting was
      independent of choice hysteresis. 

PMID- 24314734
TI  - [Qualitative and quantitative hormonal regulation in castration-resistant
      prostate cancer].
AB  - INTRODUCTION: Despite initial sensitivity to androgen deprivation, most
      metastatic prostate cancer patients will experience recurrence or progression.
      This evolution, which occurs while seric testosterone level is low, is called
      castration resistant prostate cancer (CRPC). MATERIAL AND METHODS: MEDLINE
      database was requested for French or English articles published until September
      2012 responding to the following keywords: "castration resistant", "prostatic
      neoplasms", "androgens", "testosterone", "regulat*". Here is a summary of
      relevant data concerning both qualitative and quantitative hormonal regulation.
      RESULTS: androgen blood testing is not related to tissue concentrations, as
      prostate cancer cells exhibit higher hormones levels. Despite its higher
      biological efficiency, dihydrotestosterone is not the only mediator of androgen
      dependent transcription. Androgen synthesis implies many pathways including lot
      of alternative ones. Steroidogenesis can occur out of the testicles and the
      adrenals, and maybe in tumor cell or tissue. Major and minor androgens levels, as
      those of co-repressors and activators inside the tumor cell leads to a smooth
      androgen activity modulation. Many drugs have the ability to block those
      different steps. CONCLUSION: Castration resistance reflects an androgen activity
      in tumor cells while major androgen pathway activators are lowered. Alternate
      pathway include steroids pumps, de novo synthesis by tumor cells or their
      environment, minor androgens activation by co-factors regulation. Many drugs are
      known to inhibit those escaping ways. Nowadays they are not efficient enough,
      because of other minor pathways becoming dominant. Investigations are required
      but would need new detection techniques of low androgen concentrations in blood
      as in tissues.

PMID- 24314735
TI  - [Mechanisms of resistance to CYP17A1 inhibitors in castrate resistant prostate
      cancer].
AB  - INTRODUCTION: Abiraterone acetate has increased the overall survival of patients
      with metastatic castration-resistant prostate cancer. However, despite an initial
      response to treatment, many patients develop resistance to the drug. In this
      paper we present different hypotheses that may explain the emergence of
      resistance. METHOD: This review was conducted from the PubMed database. The most
      relevant articles were selected and analyzed. RESULTS: The molecular mechanisms
      of resistance to abiraterone acetate remain largely elusive. We detailed some of
      them including the reactivation of the androgen receptor through alternative
      biosynthesis of androgens, over expression or mutation of the androgen receptor
      gene, or the action of co-activators. The over expression of CYP17A1 or the
      alteration of other genes' expression involved in steroidogenesis could also
      contribute to the resistance. CONCLUSION: Some of the molecular mechanisms
      involved in the resistance to abiraterone acetate were detailed. Better
      understanding of these mechanisms is a key step to allow the emergence of new
      therapeutic options and personalized treatments of castration resistant prostate
      cancer.

PMID- 24314736
TI  - [Corticotherapy in castration-resistant prostate cancer].
AB  - INTRODUCTION: Corticosteroids are commonly used in the treatment of prostate
      cancer resistant to castration (PCRC), partly due to the inhibitory effects on
      adrenal androgen production acting as a pituitary suppressant. METHODS: A
      literature search was conducted in PubMed/MEDLINE database using the following
      key words: prostate cancer; castration resistance; metastasis; corticotherapy.
      RESULTS: Corticosteroids exert direct anti-tumoral activities mediated by the
      glucocorticoids receptor and involving cellular/tissue functions as growth,
      apoptosis, inflammation, metastasis, differentiation and angiogenesis. As a pain
      relieving agents, corticosteroids significantly relieve PCRC clinical symptoms,
      especially those due to bone metastasis. In the comparative arm of phase II-III
      trials, corticosteroids administered daily produce a PSA decline. Among the
      adverse effects due to corticosteroids, bone loss and cardiovascular risk should
      be carefully monitored. In association with abiraterone acetate, corticosteroids
      increase overall survival in PCRC patients, and reduce the mineralocorticoid side
      effects of abiraterone. CONCLUSION: Corticosteroids in monotherapy for PCRC have
      a limited efficacy. In association with abiraterone acetate it reduces the
      mineralocorticoid toxicity and enhances the androgenic suppression.

PMID- 24314737
TI  - [Prostate cancer and new hormonal treatments: mechanism of action and main
      clinical results].
AB  - INTRODUCTION: New drugs have recently been developed, through a better
      understanding of the mechanisms involved in the progression of prostate cancer,
      including castration-resistant ones (CRPC). This article aims to describe the
      mechanisms of action of these new hormonal treatments and their major clinical
      outcomes and development programs. MATERIALS AND METHODS: A bibliographic
      research in French and English using Medline((r)) and Embase((r)) using the
      keywords "castration-resistant prostate cancer", "abiraterone acetate",
      "orteronel", "enzalutamide", and "clinical trials" was performed. RESULTS: the
      androgen signaling pathway remains the cornerstone of advanced cancers
      management. Hence, some molecules target the androgen biosynthesis, as
      abiraterone acetate and orteronel, which are selective inhibitors of the enzyme
      CYP17. Others act as antagonists of the androgen receptor: the enzalutamide, RNA
      509 and ODM201. Finally, galeterone combines the two effects. CONCLUSION:
      Progress conferred by these molecules in terms of overall survival and quality of
      life in patients with metastatic CRPC, suggest that their use at earlier stages
      of the disease could reduce morbidity and mortality from prostate cancer.
      Determining the best strategy for sequence or combination therapy to optimize the
      use of these new molecules should be investigated.

PMID- 24314738
TI  - [Choice of new drugs in castration-resistant prostate cancer: predictive factors
      and effectiveness assessment].
AB  - INTRODUCTION: Docetaxel has been the cornerstone in the treatment of castration-
      resistant prostate cancer (CRPC) since 2004. The recent and almost simultaneous
      arrival of new and effective molecules - several of which are already available
      on the market - has added to the CRPC treatment arsenal. Several studies have
      explored the optimal order in which these new treatments should be administered.
      The aim of this review was to present their respective predictive and evaluative
      factors and suggest potential administration sequences. METHODS: The PubMed
      medical literature citations database was searched using the following key words:
      prostate cancer, castration resistant, metastatic, targeted therapy, treatment
      sequence, immunotherapy and clinical trials. The reports of the most recent
      European and North American congresses were also included. RESULTS: While no
      predictive factors have been clearly identified for these new therapies to date,
      a Gleason score of not less than 8 and one or more chemotherapy sessions seemed
      to be predictive of lower efficacy for abiraterone. Promising elements for
      further investigation include the circulating tumour cell count and variation in
      this count per treatment, ERG mutation status or the intratumoural androgen
      status. Substitution criteria have not yet been reported but, as is the case with
      all hormone therapies, changes in PSA levels emerge as a valuable indicator of
      the efficacy of abiraterone. The best treatment sequence for patients who develop
      castration-resistance remains to be defined. CONCLUSION: Although new molecules
      have recently become available, the experience with their use is limited. Thus,
      no predictive markers of response rates and treatment outcomes or data concerning
      the best treatment sequence to use in patients with CRPC are as yet available.

PMID- 24314740
TI  - Maturation of cytosolic and nuclear iron-sulfur proteins.
AB  - Eukaryotic cells contain numerous cytosolic and nuclear iron-sulfur (Fe/S)
      proteins that perform key functions in metabolic catalysis, iron regulation,
      protein translation, DNA synthesis, and DNA repair. Synthesis of Fe/S clusters
      and their insertion into apoproteins are essential for viability and are
      conserved in eukaryotes. The process is catalyzed in two major steps by the CIA
      (cytosolic iron-sulfur protein assembly) machinery encompassing nine known
      proteins. First, a [4Fe-4S] cluster is assembled on a scaffold complex. This step
      requires a sulfur-containing compound from mitochondria and reducing equivalents
      from an electron transfer chain. Second, the Fe/S cluster is transferred from the
      scaffold to specific apoproteins by the CIA targeting complex. This review
      summarizes our molecular knowledge on CIA protein function during the assembly
      process. 

PMID- 24314739
TI  - [CYP17A1 inhibitors in prostate cancer: mechanisms of action independent of the
      androgenic pathway].
AB  - INTRODUCTION: The objective of this article is to review the mechanisms of action
      of abiraterone acetate, independently of the androgenic pathway. MATERIAL AND
      METHOD: A systematic review of the literature was carried out on Medline and
      Embase databases. RESULTS: Inhibition of CYP17A1 with abiraterone acetate induces
      changes in steroid metabolism, whose main component is the reduction of DHEA and
      androstenedione synthesis. This results in inhibition of androgen pathway in
      prostatic cancerous epithelial cell. Regardless of androgen activation pathway,
      abiraterone acetate could also act via an alternative mechanism of action not
      fully elucidated. Stromal cells, like tumor cells, could undergo the effects of
      CYP17A1 inhibition, resulting in blocking the production of secondary mediators
      that contribute to tumor progression. Similarly, it has been suggested that
      abiraterone acetate efficacy may be related to its ability to alter intratumoral
      concentrations of estrogen and progesterone. CONCLUSION: The validation of these
      mechanisms could contribute to improved therapeutic strategies based on the use
      of abiraterone acetate alone or in combination.

PMID- 24314741
TI  - Evaluation of an automated high-level disinfection technology for ultrasound
      transducers.
AB  - BACKGROUND: Ultrasound transducer reprocessing is required to prevent the
      transmission of infections between patients. In some regions, reprocessing
      practices are not sufficient to achieve high-level disinfection (HLD), which can
      result in contaminated probes. Furthermore, current manual HLD methods use toxic
      chemicals and are prone to operator error/variability. The development of
      automated, non-toxic HLD disinfection devices may reduce the risk of transmission
      and reduce safety risks for operators and patients. This study investigated the
      disinfection efficacy of a hydrogen peroxide-based, automated HLD device, the
      Trophon((r)) EPR, against a range of international standards. METHODS:
      Disinfection efficacy was assessed in carrier and simulated use tests against 21
      different species of bacteria, fungi and viruses. Carrier tests were performed by
      placing carriers throughout the disinfection chamber and measuring the log
      reduction in viable organisms following disinfection. These tests were performed
      according to Association of Analytical Communities International Official Methods
      and European and ASTM International Standards for bactericidal, fungicidal,
      mycobactericidal, sporicidal and virucidal disinfection. Simulated use tests
      involving the disinfection of six widely used ultrasound probe models were
      conducted according to ASTM-E1837-96 using Mycobacterium terrae as a test
      organism. RESULTS: The device satisfied criteria for HLD and sporicidal
      disinfection efficacy under all standards tested. CONCLUSIONS: Automated,
      hydrogen peroxide-based disinfection devices offer an alternative to manual
      ultrasound probe disinfection technologies. Such devices reduce the risks of
      operator error and can improve patient and operator safety by preventing exposure
      to toxic chemicals. The adoption of next-generation disinfection devices may help
      to decrease infection risk and improve patient safety.

PMID- 24314742
TI  - Empowering certified nurse's aides to improve quality of work life through a team
      communication program.
AB  - The purpose of this pilot study was to explore the impact of a certified nurse's
      aide (CNA)-led interdisciplinary teamwork and communication intervention on
      perceived quality of work environment and six-month job intentions. CNAs are
      frequently excluded from team communication and decision-making, which often
      leads to job dissatisfaction with high levels of staff turnover. Using a mixed
      quantitative and qualitative approach with pre- post-program design, the
      intervention utilized the strategy of debriefing from the national patient safety
      initiative, TeamSTEPPS. Inherent in the program design, entitled Long Term Care
      (LTC) Team Talk, was the involvement of the CNAs in the development of the
      intervention as an empowering process on two wings of a transitional care unit in
      a long-term care facility in upstate NY. CNAs' perceptions of work environment
      quality were measured using a Quality of Work Life (QWL) instrument.
      Additionally, job turnover intent within six months was assessed. Results
      indicated improved scores on nearly all QWL subscales anticipated to be impacted,
      and enhanced perceived empowerment of the CNAs on each wing albeit through
      somewhat different experiential processes. The program is highly portable and can
      potentially be implemented in a variety of long-term care settings. 

PMID- 24314743
TI  - The relationship between family obligation and religiosity on caregiving.
AB  - The purpose of this study was to examine the relationship between family
      obligation and religiosity on the positive appraisal of caregiving among African
      American, Hispanic and non-Hispanic Caucasian family caregivers of older adults.
      Roy's adaptation model guided formulation of the aims and study design. A cross
      sectional, correlational study design was employed to examine the relationship
      amongst variables for the family caregiver participants. Study participants (N =
      69) completed a demographic tool and four instruments the: (1) Katz index, (2)
      obligation scale, (3) Duke University religion index, and (4) positive appraisal
      of care scale. There was a significant correlation between family obligation and
      positive appraisal of caregiving. However, there was no relationship between the
      family caregiver's religiosity and positive appraisal of caregiving overall.
      Demographic variables were also examined to show a higher marginal mean for
      Hispanic primary caregivers in relation to the positive appraisal of caregiving.
      Future studies should consider replicating these findings in a larger sample to
      provide health care professionals with substantial evidence to incorporate
      culturally sensitive interventions aimed at promoting positive outcomes and
      healthy family behaviors. 

PMID- 24314744
TI  - Change of short-term memory effect in acute ischemic ventricular myocardium: a
      computational study.
AB  - The ionic mechanism of change in short-term memory (STM) during acute myocardial
      ischemia has not been well understood. In this paper, an advanced guinea pig
      ventricular model developed by Luo and Rudy was used to investigate STM property
      of ischemic ventricular myocardium. STM response was calculated by testing the
      time to reach steady-state action potential duration (APD) after an abrupt
      shortening of basic cycling length (BCL) in the pacing protocol. Electrical
      restitution curves (RCs), which can simultaneously visualize multiple aspects of
      APD restitution and STM, were obtained from dynamic and local S1S2 restitution
      portrait (RP), which consist of a longer interval stimulus (S1) and a shorter
      interval stimulus (S2). The angle between dynamic RC and local S1S2 RC reflects
      the amount of STM. Our results indicated that compared with control (normal)
      condition, time constant of STM response in the ischemic condition decreased
      significantly. Meanwhile the angle which reflects STM amount is less in ischemic
      model than that in control model. By tracking the effect of ischemia on
      intracellular ion concentration and membrane currents, we declared that changes
      in membrane currents caused by ischemia exert subtle influences on STM; it is
      only the decline of intracellular calcium concentration that give rise to the
      most decrement of STM. 

PMID- 24314745
TI  - Downloads as a possible index of impact?

PMID- 24314746
TI  - Withanolides from Jaborosa caulescens var. bipinnatifida.
AB  - Withanolides 2,3-dihydrotrechonolide A (1) and 2,3-dihydro-21-hydroxytrechonolide
      A (2) were isolated along with two known withanolides trechonolide A (3) and
      jaborosalactone 39 (4) from Jaborosa caulescens var. bipinnatifida (Solanaceae).
      The structures of 1-2 were elucidated through 2D NMR and other spectroscopic
      techniques. In addition, the structure of withanolide 1 was confirmed by X-ray
      crystallographic analysis. 

PMID- 24314747
TI  - Genetic heterogeneity of hemoglobin AEBart's disease: a large cohort data from a
      single referral center in northeast Thailand.
AB  - AEBart's disease is a thalassemia intermedia usually characterized by the
      interaction of alpha(0)-thalassemia with either deletional or non-deletional
      alpha(+)-thalassemia in Hb E heterozygote. Genotypic and phenotypic features are
      heterogeneous. We studied the hematologic and molecular characteristics of this
      disease in a cohort of 173 Thai patients encountered at our center in northeast
      Thailand. Hemoglobin and DNA analyses identified patients with deletional
      AEBart's disease (n=84), Hb Constant Spring AEBart's disease (n=81), Hb Pakse
      AEBart's disease (n=5), AEBart's disease with codon 30 mutation (n=1) and two
      hitherto un-described forms of AEBart's disease due to interaction of Hb E
      heterozygote and alpha(0)-thalassemia with the -alpha(16.6)kb deletional alpha(+)
      thalassemia (n=1) and Hb Q-Thailand (n=1). Different phenotypic expression of
      these AEBart's diseases with low Hb, Hct and MCV and increased RDW values with
      marked reduction in Hb E levels were observed. It was found that all these forms
      of AEBart's disease showed similar thalassemia intermedia phenotypes but those
      with non-deletional forms were relatively more anemic. Our data confirm that in
      such area with high prevalence of hemoglobinopathies such as Southeast Asia,
      identification of rare thalassemia alleles in a thalassemia intermedia patient
      should not be ignored. Careful consideration of different phenotypic expression
      may help in providing presumptive diagnosis of this disease where access to
      molecular testing is limited. However, molecular diagnostic is useful for
      predicting the clinical outcome and improving genetic counseling of these complex
      hemoglobinopathies. 

PMID- 24314748
TI  - Multiple physical stresses induce gamma-globin gene expression and fetal
      hemoglobin production in erythroid cells.
AB  - Increased fetal hemoglobin (HbF) expression is beneficial for beta
      hemoglobinopathy patients; however, current inducing agents do not possess the
      ideal combination of efficacy, safety and ease of use. Better understanding the
      mechanisms involved in gamma-globin gene induction is critical for designing
      improved therapies, as no complete mechanism for any inducing agent has been
      identified. Given the cytotoxic nature of most known inducing drugs, we
      hypothesized that gamma-globin is a cell stress response gene, and that induction
      occurs via activation of cell stress signaling pathways. We tested this
      hypothesis by investigating the ability of physical stresses including heat-shock
      (HS), UV- and X-irradiation and osmotic shock to increase gamma-globin gene
      expression in erythroid cells. Experiments in K562 and KU812 cells showed that
      each of these stresses increased steady-state gamma-globin mRNA levels, but only
      after 3-5days of treatments. HS and UV also increased gamma-globin mRNA and HbF
      levels in differentiating primary human erythroid cells. Mechanistic studies
      showed that HS affects gamma-globin mRNA at multiple levels, including nascent
      transcription and transcript stability, and that induction is dependent on
      neither the master regulator of the canonical HS response, HSF1, nor p38 MAPK.
      Inhibitor panel testing identified PI3K inhibitor LY294002 as a novel inducing
      agent and revealed potential roles for NFkappaB and VEGFR/PDGFR/Raf kinases in HS
      mediated gamma-globin gene induction. These findings suggest that cell stress
      signaling pathways play an important role in gamma-globin gene induction and may
      provide novel targets for the pharmacologic induction of fetal hemoglobin. 

PMID- 24314749
TI  - Cardiac tuberculoma presenting as thrombotic thrombocytopenic purpura-hemolytic
      uremic syndrome.
AB  - Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a
      unique multisystem syndrome. It can present with either chronic or subacute
      infections. Tuberculosis (TB) is a chronic infection that has been reported to
      present with TTP-HUS as tuberculous endocarditis in the presence of
      immunodeficiency and implanted medical devices in regions where TB is endemic.
      Tuberculomas are space occupying lesions most commonly found in the brain in
      immunocompromised individuals. Herein, we present a rare association of
      tuberculosis with endocarditis manifesting as a tuberculoma and presenting as TTP
      HUS in an immunocompetent patient and resident of the United States. 

PMID- 24314750
TI  - Therapeutic potential of agomelatine in epilepsy and epileptic complications.
AB  - Epilepsy is a chronic neurologic disorder which often induces numerous adverse
      long-term neurologic effects, such as behavioral and cognitive deficits,
      increased predisposition to additional seizures, and cell injury or death.
      Cognitive dysfunction, depression, anxiety and sleep disorders are some of the
      highly prevalent and most disabling complications of epilepsy. The mechanisms
      that lead to the generation of epileptic comorbidities are poorly understood.
      Treatment for epileptic complications still remains a challenge because of the
      poor adherence and drug interactions associated with multi drug prescriptions and
      also for the fear of worsening seizures by the individual medications for
      complications. Melatonin, an endogenous hormone secreted by pineal gland has a
      prominent role in epilepsy. Agomelatine is a novel antidepressant which acts as
      melatonin MT1 and MT2 receptor agonist and serotonin 5Ht2C receptor antagonist.
      The combined action at MT1/2 and 5HT2C receptors, reduction in the depolarization
      evoked release of glutamate, strong neuroprotective action and possible
      antioxidant properties of agomelatine could make it a potential agent in the
      treatment of epilepsy. The effect of agomelatine on hippocampal neuronal cell
      survival and neurogenesis, neuroprotective effect in hippocampus and frontal
      cortex and the antioxidant potential may contribute to the protective action of
      agomelatine against epilepsy induced memory decline. Agomelatine is proven to be
      an antidepressant and it has relieved anxiety symptoms and improved the quality
      of sleep in patients with depressive disorder. The action of agomelatine as a
      melatonin agonist and the consequent circadian resynchronizing property as well
      as its action as 5-HT2C receptor antagonist, could possibly suggest an
      antidepressant and anxiolytic action of agomelatine in epilepsy induced
      depressive behavior and anxiety. Since one of the many causes of sleep disruption
      in epilepsy is circadian rhythm disturbances and sleep promoting and circadian
      effects of melatonin is attributed to the MT1 and MT2 subtypes of human melatonin
      receptors, agomelatine may also have a promising effect on epilepsy induced sleep
      disruptions. Thus with all these potential pharmacological actions, agomelatine
      could be recommended as a potential drug to treat epilepsy and its complications.

PMID- 24314751
TI  - Management of infections related to totally implantable venous-access ports:
      challenges and perspectives.
AB  - Use of totally implantable venous-access ports (TIVAPs) is standard practice for
      patients with diseases such as solid-tumour cancers, haematological malignancies,
      and chronic digestive diseases. Use of TIVAPs allows long-term administration of
      venotoxic compounds, improves patients' quality of life, and reduces the risk of
      infection. Microbial contamination, formation of pathogenic biofilms, and
      infection, however, are associated with morbidity, mortality, and increased
      health-care costs. Local and systemic complications or infections related to
      specific pathogens might lead to device removal. Alternatively, conservative
      treatment with combined systemic antibiotics and antibiotic lock therapy might be
      useful. We discuss in-vitro and in-vivo basic and clinical research findings on
      the epidemiology, diagnosis, and prevention of TIVAP-related infections, the
      current challenges to management, promising strategies, and some treatments in
      development that are likely to improve outcomes of TIVAP-related infections, with
      a particular focus on antibiotic lock therapy. 

PMID- 24314752
TI  - Diaphragmatic dysfunction in Collagen VI myopathies.
AB  - Collagen VI-related myopathies are hereditary disorders causing progressive
      restrictive respiratory insufficiency. Specific diaphragm involvement has been
      suggested by a drop in supine volumes. This pilot study aimed at characterizing
      the respiratory muscle phenotype in patients with COL6A1-3 genes mutations. Lung
      function, blood gases, muscle strength and respiratory mechanics were measured in
      7 patients between 2002 and 2012. Patients were classified as Early-Severe (n =
      3), Moderate-Progressive (n = 2) and Mild (n = 2) according to clinical disease
      presentation. Seven patients (aged 6-28) were evaluated. Forced vital capacity
      distinguished the Mild group (>60% predicted) from the two other groups (<50%
      predicted). This distinction was also possible using the motor function measure
      scale. Diaphragmatic dysfunction at rest was observed in all the Early-Severe and
      Moderate-Progressive patients. During a voluntary sniff maneuver diaphragmatic
      dysfunction was observed in all patients, as assessed by a negative gastric
      pressure. All patients had diaphragmatic fatigue assessed by a tension-time index
      over the threshold of 0.15. Diaphragmatic dysfunction during a maximal voluntary
      maneuver and diaphragmatic fatigue are constant features in Collagen VI
      myopathies. These observations can assist the diagnosis and should be taken in
      account for the clinical management, with the early detection of sleep-disordered
      breathing.

PMID- 24314753
TI  - Clinical neurophysiology in neonatology.

PMID- 24314754
TI  - The electroencephalogram of the full-term newborn: review of normal features and
      hypoxic-ischemic encephalopathy patterns.
AB  - OBJECTIVE: The objective of this study is to specify, by reference to the normal
      newborn, the current contribution of the electroencephalogram (EEG) to the
      diagnosis and prognosis of hypoxic-ischemic encephalopathy (HIE) in the full-term
      newborn. Both digitized traditional EEG and cerebral function monitoring will be
      considered. DISCUSSION: A good knowledge of the EEG features of the sleep-wake
      cycle (SWC) is a prerequisite. We first describe the main features of normal and
      pathological EEGs. Very early recordings (before 6hours of life) are needed to
      indicate any required neuroprotective (hypothermia) and other (sedation,
      anticonvulsivants) treatments. CONCLUSIONS: Between the normal or near-normal
      tracings, which are associated with a good prognosis, and the very pathological
      ones (inactive, paroxysmal), which are associated with a poor vital or
      neurological prognosis, the interpretation of "intermediate" tracings--mainly
      represented by other types of discontinuous tracings--must take into account
      characteristics such as bursts and discontinuities, postnatal age, evolution of
      successive tracings, and treatments.

PMID- 24314755
TI  - Cognitive outcome at 5 years in very premature children without severe early
      cerebral abnormalities. Relationships with EEG at 6 weeks after birth.
AB  - AIMS OF THE STUDY: This prospective study aimed to analyze the relationship
      between EEG at 6 weeks after birth and cognitive outcome at the age of 5 in
      children born very preterm who did not present with severe neonatal cerebral
      abnormalities. PATIENTS AND METHODS: EEGs were recorded at 6 weeks of age in
      infants born <29 weeks of gestation or weighing <1000 g at birth. At 5 years,
      study participants underwent a neurological assessment and cognitive evaluation
      with the Kaufman Assessment Battery for Children (K-ABC). RESULTS: Fifty-eight
      children had an EEG at 6 weeks after birth. Fifty-one were evaluated at 5 years.
      Twenty-six children (51.0%) had one or more disabilities: neuromotor, sensory,
      behavioral, and/or cognitive. Children with EEG abnormalities had significantly
      more disabilities (20 of 25, 80%) than children with normal EEG (6 of 26, 23%)
      (P=0.0002). Thirty-five children underwent complete K-ABC assessment. Multiple
      linear regression analysis indicated a significant relationship between the
      overall EEG abnormalities (normal, dysmature, and/or disorganized) and two
      scales: mental processing composite (MPC) scales (P=0.0121), and sequential
      processing scales (P=0.0012). Dysmature EEGs were more predictive of lower MPC
      and sequential processing scales than disorganized EEGs. Immature occipital slow
      waves (i.e., too high for conceptional age) were consistently recorded in
      children with dysmature EEGs and associated with the lowest K-ABC scores.
      CONCLUSION: EEG abnormalities recorded at 6 weeks after birth, such as immature
      occipital slow waves, were associated with later cognitive impairments. EEG at 6
      weeks can be an early and reliable tool for assessing the risk of future
      cognitive impairment.

PMID- 24314756
TI  - Acute paralysis after seafood ingestion.
AB  - The first European case of tetrodotoxin intoxication is reported in a patient who
      ingested a trumpet shellfish from the Atlantic Ocean in Southern Europe. He
      suffered general acute paralysis with respiratory failure necessitating
      ventilation. Early neurophysiologic studies showed complete peripheral nerve
      inexcitability, with no recordable sensory or motor responses, and normal
      electroencephalography. Tetrodotoxin was detected in high quantities in the
      patient's blood and urine through high performance liquid chromatography-mass
      spectrometry analysis. Seventy-two hours after admission the patient recovered
      normal strength, reflexes and sensation. 

PMID- 24314757
TI  - Iron depletion induced by bloodletting and followed by rhEPO administration as a
      therapeutic strategy in progressive multiple sclerosis: a pilot, open-label study
      with neurophysiological measurements.
AB  - OBJECTIVES: To evaluate the concept that iron depletion (ID) induced by
      bloodletting and followed by recombinant human erythropoietin (rhEPO)
      administration could be a therapeutic strategy in progressive multiple sclerosis
      (PMS) and that it could be assessed by neurophysiological measurements. PATIENTS
      AND METHODS: In four patients with PMS, bloodletting was performed until ID was
      induced, and then rhEPO was administered (300 UI/kg/week). The changes induced by
      the treatment were assessed by clinical scores, biological tests, and
      neurophysiological study of cortical excitability using transcranial magnetic
      stimulation techniques. RESULTS: The treatment was well tolerated except for
      muscle cramps and one popliteal vein thrombosis in a patient confined to chair.
      ID was obtained within 28 weeks and was associated with endogenous production of
      EPO. No bloodletting was further required during a six-month period after
      introduction of rhEPO. At the end of the follow-up (up to one year), fatigue and
      walking capacities tended to improve in two patients. Neurophysiological changes
      were characterized by an increased cortical excitability, including a decrease of
      motor thresholds and an enhancement of intracortical facilitation and
      cerebellothalamocortical inhibition. CONCLUSIONS: The combined ID-rhEPO therapy
      could authorize a prolonged administration of rhEPO in PMS patients, able to
      modify cortical excitability of the glutamatergic and gabaergic circuits. These
      preliminary data are encouraging to design a larger, controlled therapeutical
      trial to assess the value of such a strategy to improve functional symptoms in
      PMS patients, and maybe to prevent axonal degeneration. Neurophysiological
      measurements based on cortical excitability studies could provide sensitive
      parameters to evaluate treatment-induced changes in this context.

PMID- 24314758
TI  - Comprehensive analysis of melanogenesis and proliferation potential of melanocyte
      lineage in solar lentigines.
AB  - BACKGROUND: Solar lentigines (SLs) are characterized by hyperpigmented macules,
      commonly seen on sun-exposed areas of the skin. Although it has been reported
      that an increase in the number of melanocytes and epidermal melanin content was
      observed in the lesions, the following questions remain to be answered: (1) Is
      acceleration of melanogenesis in the epidermis caused by an increased number of
      melanocytes or the high melanogenic potential of each melanocyte? (2) Why does
      the number of melanocytes increase? OBJECTIVE: To elucidate the pathogenic
      mechanism of SLs by investigating the number, melanogenic potential and
      proliferation status of the melanocyte lineage in healthy skin and SL lesions.
      METHODS: Immunostaining for melanocyte lineage markers (tyrosinase, MART-1, MITF,
      and Frizzled-4) and a proliferation marker, Ki67, was performed on skin sections,
      and the obtained images were analyzed by image analysis software. RESULTS: The
      expression level of tyrosinase to MART-1 of each melanocyte was significantly
      higher in SL lesions than healthy skin. The numbers of melanocytes in the
      epidermis, melanoblasts in the hair follicular infundibulum and melanocyte stem
      cells in the bulge region were increased in SL; however, no significant
      difference was observed in the Ki67-positive rate of these cells. CONCLUSION: The
      melanogenic potential of each melanocyte was elevated in SL lesions. It was
      suggested that the increased number of melanocytes in the SL epidermis might be
      attributed to the abnormal increase of melanocyte stem cells in the bulge.

PMID- 24314759
TI  - Transcriptional profiling of epidermal barrier formation in vitro.
AB  - BACKGROUND: Barrier function is integral to the health of epithelial tissues.
      Currently, there is a broad need to develop and improve our knowledge with regard
      to barrier function for reversal of mild skin irritation and dryness. However,
      there are few in vitro models that incorporate modulations of both lipids and
      epidermal differentiation programs for pre-clinical testing to aid in the
      understanding of barrier health. OBJECTIVE: We have generated a reconstituted
      epidermis on a decellularized dermis (DED) and characterized its barrier
      properties relative to human epidermis in order to determine its utility for
      modeling barrier formation and repair. METHODS: We followed the process of
      epidermal differentiation and barrier formation through immunocytochemistry and
      transcriptional profiling. We examined barrier functionality through measurements
      of surface pH, lipid composition, stratum corneum water content, and the ability
      to demonstrate topical dose-dependent exclusion of surfactant. RESULTS:
      Transcriptional profiling of the epidermal model during its formation reveals
      temporal patterns of gene expression associated with processes regulating barrier
      function. The profiling is supported by gradual formation and maturation of a
      stratum corneum and expression of appropriate markers of epidermis development.
      The model displays a functional barrier and a water gradient between the stratum
      corneum and viable layers, as determined by confocal Raman spectroscopy. The
      stratum corneum layer displays a normal acidic pH and an appropriate composition
      of barrier lipids. CONCLUSION: The epidermal model demonstrates its utility as an
      investigative tool for barrier health and provides a window into the
      transcriptional regulation of multiple aspects of barrier formation.

PMID- 24314760
TI  - Sweep visually evoked potentials and visual findings in children with West
      syndrome.
AB  - BACKGROUND: West syndrome (WS) is a type of early childhood epilepsy
      characterized by progressive neurological development deterioration that includes
      vision. AIM: To demonstrate the clinical importance of grating visual acuity
      thresholds (GVA) measurement by sweep visually evoked potentials technique (sweep
      VEP) as a reliable tool for evaluation of the visual cortex status in WS
      children. METHODS: This is a retrospective study of the best-corrected binocular
      GVA and ophthalmological features of WS children referred for the Laboratory of
      Clinical Electrophysiology of Vision of UNIFESP from 1998 to 2012 (Committee on
      Ethics in Research of UNIFESP n degrees  0349/08). The GVA deficit was calculated
      by subtracting binocular GVA score (logMAR units) of each patient from the median
      values of age norms from our own lab and classified as mild (0.1-0.39 logMAR),
      moderate (0.40-0.80 logMAR) or severe (>0.81 logMAR). Associated ophthalmological
      features were also described. RESULTS: Data from 30 WS children (age from 6 to
      108 months, median = 14.5 months, mean +/- SD = 22.0 +/- 22.1 months; 19 male)
      were analyzed. The majority presented severe GVA deficit (0.15-1.44 logMAR; mean
      +/- SD = 0.82 +/- 0.32 logMAR; median = 0.82 logMAR), poor visual behavior, high
      prevalence of strabismus and great variability in ocular positioning. The GVA
      deficit did not vary according to gender (P = .8022), WS type (P = .908), birth
      age (P = .2881), perinatal oxygenation (P = .7692), visual behavior (P = .8789),
      ocular motility (P = .1821), nystagmus (P = .2868), risk of drug-induced
      retinopathy (P = .4632) and participation in early visual stimulation therapy (P
      = .9010). CONCLUSIONS: The sweep-VEP technique is a reliable tool to classify
      visual system impairment in WS children, in agreement with the poor visual
      behavior exhibited by them.

PMID- 24314761
TI  - A proposed diagnostic approach for infantile spasms based on a spectrum of
      variable aetiology.
AB  - AIM: To identify the aetiology of patients with infantile spasms and propose
      practical guidelines for diagnostic strategies. METHOD: We performed a
      retrospective study of children with West syndrome. Prenatal and birth medical
      history, characteristics of epilepsy, psychomotor development, biological and
      genetic screening, and aetiology were reported. Brain MRI was performed at least
      once and was repeated after two years of age if no aetiology was identified.
      RESULTS: Eighty children were included. Aetiology was identified in 40 children:
      17 with acquired cause (seven with stroke and six with hypoxic-ischaemic
      encephalopathy) and 23 with developmental pathology (seven with tuberous
      sclerosis, eight with cerebral malformations, and eight with various genetic
      abnormalities). The yield of brain imaging was high, providing a diagnosis for 32
      patients. Two subtle brain lesions were detected only after two years of age,
      based on subsequent MRI. Genetic testing provided a diagnosis for the remaining
      eight patients. INTERPRETATION: Although this is a retrospective study, the
      results provide a basis to review the aetiology of infantile spasms and confirm
      the role of cerebral MRI in first-line diagnosis. Cases with a genetic aetiology
      have been diagnosed with increasing frequency due to better diagnostic
      capabilities. We propose guidelines for a practical diagnostic approach and
      discuss the relevant use of genetics in the future.

PMID- 24314762
TI  - Magnetic resonance image findings of primary intradural Ewing sarcoma of the
      cauda equina: case report and review of the literature.
AB  - BACKGROUND CONTEXT: Involvement of the cauda equina in Ewing sarcoma (ES) is
      extremely rare, and only few cases are reported in literature. However, ES of
      cauda equina shares some neuroradiological features with other neoplasms that can
      involve the intradural space. Therefore, differential diagnosis with other tumors
      of cauda equina should be considered by neuroradiologists and neurosurgeons to
      provide appropriate treatment. PURPOSE: To present a rare case of intradural
      extramedullary primary ES. STUDY DESIGN: Case report. METHODS: We report a case
      of a 44-year-old woman presenting with the rapid onset of cauda equina syndrome.
      Radiological analysis showed multiple intradural masses, extending from L1 to S3
      level. After radical surgery, lesions were histologically defined as ES. We
      present a literature review, analyzing magnetic resonance image (MRI) features of
      primary intradural ES of the cauda equina. RESULTS: Four cases of primitive ES
      arising from the cauda equina have been reported in the literature. CONCLUSIONS:
      Because of the low number of reported cases, it is not possible to describe
      pathognomonic MRI findings for intradural ES of the cauda equina. However, few
      tumors show similar MRI features. Therefore, despite its rarity, intradural ES
      should be taken into account in the differential diagnosis of spinal tumors
      involving cauda equina.

PMID- 24314763
TI  - Anterior debridement, decompression, bone grafting, and instrumentation for lower
      cervical spine tuberculosis.
AB  - BACKGROUND CONTEXT: Cervical spine tuberculosis (TB) is uncommon, accounting for
      3% to 5% of spinal TB. Although the development of anti-TB chemotherapy decreases
      the mortality rate significantly, it may not be applicable for all situations,
      especially for those with risk of instability, progression of neurologic deficit,
      and failure of medical treatment. PURPOSE: To evaluate the efficacy of anterior
      instrumentation after debridement and bone grafting in patients with lower
      cervical TB over a 5-year period at a single institution. STUDY DESIGN: A
      retrospective study examining the results of anterior debridement, decompression,
      bone grafting, and instrumentation for lower cervical spine TB. PATIENT SAMPLE:
      The procedure was performed in 25 patients. OUTCOME MEASURES: The clinical
      outcomes of infection activity, deformity, pain, and neurologic function were
      evaluated using erythrocyte sedimentation rate value and C-reactive protein
      value, kyphotic angle, visual analog scale pain score, and Frankel grade,
      respectively. METHODS: Between 2005 and 2010, 25 patients (18 males and seven
      females; average age, 39 years) with lower cervical spine tuberculosis (C3-C7)
      underwent anterior debridement, decompression, bone grafting, and
      instrumentation. The average follow-up period was 37.4 months (range 24-57
      months). The medical records and radiographic findings of the patients were
      reviewed. RESULTS: There were three patients who had involvement of one vertebra,
      18 had two vertebrae of involvement, and four had three vertebrae of involvement.
      Before surgery, there were three patients with Frankel grade B, five with grade
      C, 12 with grade D, and five with grade E. During the last follow-up examination,
      in 20 patients with neurological deficit, 11 patients improved one grade, six
      patients improved two grades, one patient improved three grades, and the
      neurologic status remained unchanged in two patients. Stable bone union was
      observed in all cases and the average time required for fusion was 6.8 months.
      The kyphosis Cobb angle improved from the preoperative average of 15.48 degrees 
      (range 0 degrees -55 degrees ) to a postoperative average of -4.8 degrees  (range
      -12 degrees  to 4 degrees ) and there was no significant correction loss during
      the follow-up period. During the follow-up period, there were no grafts or
      instrumentation-related stabilization problems. There was no other recurrence of
      TB infection. CONCLUSIONS: Anterior debridement, decompression, bone grafting,
      and instrumentation are safe and effective methods in the surgical management of
      lower cervical spine tuberculosis.

PMID- 24314764
TI  - Pathomorphological description of the shunted portion of a filum terminale
      arteriovenous fistula.
AB  - BACKGROUND CONTEXT: The clinical morphology of a filum terminale arteriovenous
      fistula (f-AVF) is well known; however, pathological details of the fistulized
      portion are unknown. Herein, we report the pathological findings of the f-AVF.
      STUDY DESIGN: Case report and literature review. PURPOSE: To present a detailed
      pathological examination of the fistulized portion of the f-AVF. METHODS: A 71
      year-old man presented with gradually worsening bilateral foot paresthesias and
      anal dysesthesia. T2-weighted magnetic resonance imaging showed flow voids
      surrounding an edematous conus medullaris and cauda equina with spinal stenosis
      at L3-L4 and L4-L5. Spinal digital subtraction angiography demonstrated an f-AVF
      fed by the left T9 intercostal artery. RESULTS: We performed laminotomies of L3
      and L4 to open the dura mater and found a hypertrophic filum terminale. It was
      resected, leaving a length of 2 cm between the abnormal proximal end and normal
      distal end. The f-AVF completely disappeared after the surgery. On pathological
      examination, the filum terminale included two vessels at the proximal end and one
      at the distal end. At the proximal end, immunostaining showed one vessel that was
      definitively an artery with both an internal elastic membrane (IEM) and smooth
      muscle. The other was a vein and lacked an IEM. On the distal side, the collagen
      fibers gradually increased, the IEM partially disappeared from the arterial wall,
      and the vein became arterialized with a thin IEM. At the distal end the two
      vessels joined. Therefore, we speculated that the fistulized portion of the f-AVF
      was not a fistula point but had some lengths where the artery had characteristics
      of a vein and there was venous arterialization. CONCLUSIONS: The filum
      arteriovenous shunting occurred at the portion where there was venous
      arterialization and the artery had the characteristics of a vein. Therefore,
      resecting the filum terminale requires more proximal from the normal distal end.

PMID- 24314765
TI  - Use of Piezosurgery for removal of retrovertebral body osteophytes in anterior
      cervical discectomy.
AB  - BACKGROUND CONTEXT: The relatively new technique of Piezosurgery is based on
      microvibrations, generated by the piezoelectrical effect, which results in
      selective bone cutting with preservation of adjacent soft tissue. PURPOSE: To
      study the applicability of Piezosurgery in anterior cervical discectomy with
      fusion (ACDF) surgery. STUDY DESIGN/SETTING: Prospective clinical study at the
      neurosurgical department of the University of Freiburg, Germany. PATIENT SAMPLE:
      Nine patients with cervical disc herniation and retrovertebral osteophytes who
      underwent ACDF surgery. OUTCOME MEASURES: Piezosurgery was evaluated with respect
      to practicability, safety, preciseness of bone cutting, and preservation of
      adjacent neurovascular tissue. Pre- and postoperative clinical and radiological
      data were assessed. METHODS: Piezosurgery was supportively used in ACDF in nine
      patients with either radiculopathy or myelopathy from disc herniation or ventral
      osteophytes. After discectomy, osteophytes were removed with Piezosurgery to
      decompress the spinal canal and the foramina. Angled inserts were used, allowing
      for cutting even retrovertebral osteophytes. RESULTS: In all nine cases,
      Piezosurgery cut bone selectively with no damage to nerve roots, dura, or
      posterior longitudinal ligament. None of the patients experienced any new
      neurological deficit after the operation. The handling of the instrument was safe
      and the cut precise. Osteophytic spurs, even retrovertebral ones that generally
      only can be approached via corpectomies, could be safely removed because of the
      angled inserts through the disc space. Currently, a slightly prolonged operation
      time was observed for Piezosurgery. Furthermore, the design of the handpiece
      could be further improved to facilitate the intraoperative handling in ACDF.
      CONCLUSIONS: Piezosurgery proved to be a useful and safe technique for selective
      bone cutting and removal of osteophytes with preservation of neuronal and soft
      tissue in ACDF. In particular, the angled inserts were effective in cutting bone
      spurs behind the adjacent vertebra which cannot be reached with conventional
      rotating burs.

PMID- 24314766
TI  - Basivertebral foramen could be connected with intravertebral cleft: a potential
      risk factor of cement leakage in percutaneous kyphoplasty.
AB  - BACKGROUND CONTEXT: Among different types of cement leakage in percutaneous
      kyphoplasty (PKP) for osteoporotic vertebral body compression fractures, leaks
      into the spinal canal are considered to be the most common complication. One
      potential structure causing this type of cement leakage is the potential
      connection between the basivertebral foramen and the intravertebral cleft, which
      is revealed clearly on magnetic resonance (MR) images, but is often ignored in
      the literature. PURPOSE: The purpose of this study is to assess the incidence
      rate of different types of cement leakage in PKP with or without intravertebral
      clefts and to determine whether the basivertebral foramen could be connected to
      the intravertebral cleft. STUDY DESIGN: This study is a retrospective assessment
      of the presence of an intravertebral cleft in osteoporotic vertebral bodies and
      the different types of cement leakage after PKP on radiographs, computed
      tomographic (CT) scans, and MR images. PATIENT SAMPLE: A total of 164 consecutive
      patients underwent PKP to treat 204 osteoporotic vertebral compression fractures.
      OUTCOME MEASURES: Outcome measures include the occurrence of different types of
      cement leakage in the groups with an intravertebral cleft and without
      intravertebral clefts. METHODS: A total of 204 vertebrae in 164 consecutive
      patients who underwent PKP to treat osteoporotic vertebral compression fractures
      were classified into two patterns based on preoperative radiographs, CT scans,
      and/or MR images of the treated levels: cleft pattern (with an intravertebral
      cleft in the vertebral body) and trabecular pattern (without intravertebral
      clefts). When an intravertebral cleft was identified, the investigators examined
      the basivertebral foramen and looked for a communication between the two
      structures on three-dimensional CT scans and MR images. On direct postoperative
      images, the patterns of cement leakage were classified as five types: type A,
      through a cortical defect into the paraspinal soft tissues; type B, through the
      basivertebral foramen; type C, via the needle channel; type D, through a cortical
      defect into the disc space; and type E, via the paravertebral vein. The
      association of the distribution of the cement leakage and the presence of an
      intravertebral cleft was analyzed retrospectively. Moreover, the association of
      type B leakage with the communication between the basivertebral foramen and the
      intravertebral cleft was also assessed. RESULTS: The average interobserver kappa
      values for determining the type of cement leakage and the presence of
      intravertebral cleft were 0.916 (range, 0.792-1) and 0.935, respectively. In 41
      of 204 vertebrae (19.9%), an intravertebral cleft was confirmed on preoperative
      images. A communication between the intravertebral cleft and the basivertebral
      foramen was seen in 10 vertebrae (24.4%). Cement leakage was 36.2% in the group
      with a trabecular pattern and 41.5% in the group with a cleft pattern (p>.05).
      Leaks through the basivertebral foramen (type B; N=30, 14.7%) and through
      cortical defects into the disc space (type D; N=14, 6.9%) were more common than
      other types. Twenty of 163 vertebrae with the trabecular pattern (12.3%) and 10
      of 41 vertebrae with the cleft pattern (24.4%) were identified as type B leaks,
      which reached statistical significance (p<.05). There was no statistical
      difference between the trabecular pattern and the cleft pattern on other types of
      leaks. CONCLUSIONS: Type B leaks are more common in vertebrae with an
      intravertebral cleft, which supports the presence of a connection between an
      intravertebral cleft and the basivertebral foramen. Thus, care must be taken when
      PKP is performed in these patients to avoid direct cement leakage into the spinal
      canal through the basivertebral foramen.

PMID- 24314768
TI  - Systemic antitumor immune response following reconstruction using frozen
      autografts for total en bloc spondylectomy.
AB  - BACKGROUND CONTEXT: Total en bloc spondylectomy (TES) is a surgery designed to
      achieve complete resection of a malignant spinal tumor, such as spinal
      metastasis. Although this procedure decreases the rate of local recurrence, it is
      questionable whether local control prolongs a patient's survival. In cryosurgery,
      antitumor immunity is activated after percutaneous cryoablation of tumors. We
      applied this tumor-induced cryoimmunology to TES surgery and developed a "second
      generation TES" that brings about TES enhancing antitumor immunity to prolong a
      patient's survival. PURPOSE: To present a second-generation TES applied tumor
      induced cryoimmunology and assess the immunity-enhancing effect after
      implementing this surgery. STUDY DESIGN: This is a retrospective review of
      prospectively collected data. PATIENT SAMPLE: The sample consisted of 65
      consecutive patients who underwent second-generation TES. OUTCOME MEASURES:
      Interferon gamma (IFN-gamma) and interleukin-12 (IL-12) before surgery and at
      both 1 and 3 months after surgery was used to assess the immunity-enhancing
      effect. METHODS: In second-generation TES, instead of harvesting autograft from
      the ilium or fibula, the resected lamina and vertebral body from TES are frozen
      using liquid nitrogen and used as grafted bone for spinal reconstruction. In the
      most recent 33 of the 65 cases, in addition to the TES procedure, a small amount
      of the tumor tissue from the resected tumor-bearing vertebra was also placed into
      liquid nitrogen. This small amount of tumor tissue was then implanted
      subcutaneously on one side of the axilla at the end of the TES surgery. In 60 of
      65 cases, measurement of IFN-gamma and IL-12 was performed. RESULTS: IFN-gamma
      increased after surgery in 45 (75%) of 60 cases. The mean IFN-gamma relative
      concentrations at both 1 and 3 months after surgery, as compared with before
      surgery, were significantly higher (284%+/-596% and 275%+/-354%: p<.05). IL-12
      increased after surgery in 44 (73.3%) of 60 cases. The mean IL-12 relative
      concentrations at both 1 and 3 months after surgery, as compared with before
      surgery, were significantly higher (277%+/-385% and 486%+/-1032%: p>.05 and
      p<.01) at 3 months. At final follow-up, 13 of the 65 patients died due to
      progression of metastases (mean 12.6 months after TES), 15 remained free from
      disease, and 36 patients were alive with disease. CONCLUSIONS: The second
      generation TES using frozen tumor-bearing autograft inside a cage affords three
      benefits: (1) no pain at the bone harvest site, (2) shortening of operation time,
      and (3) decrease of blood loss. Moreover, our results show that second-generation
      TES provides not only a local radical cure but also a systemic immunological
      enhancement.

PMID- 24314767
TI  - The evaluation of lumbar multifidus muscle function via palpation: reliability
      and validity of a new clinical test.
AB  - BACKGROUND CONTEXT: The lumbar multifidus muscle provides an important
      contribution to lumbar spine stability, and the restoration of lumbar multifidus
      function is a frequent goal of rehabilitation. Currently, there are no reliable
      and valid physical examination procedures available to assess lumbar multifidus
      function among patients with low back pain. PURPOSE: To examine the inter-rater
      reliability and concurrent validity of the multifidus lift test (MLT) to identify
      lumbar multifidus dysfunction among patients with low back pain. STUDY
      DESIGN/SETTING: A cross-sectional analysis of reliability and concurrent validity
      performed in a university outpatient research facility. PATIENT SAMPLE: Thirty
      two persons aged 18 to 60 years with current low back pain and a minimum modified
      Oswestry disability score of 20%. Study participants were excluded if they
      reported a history of lumbar spine surgery, lumbar radiculopathy, medical red
      flags, osteoporosis, or had recently been treated with spinal manipulation or
      trunk stabilization exercises. OUTCOME MEASURES: Concurrent measures of lumbar
      multifidus muscle function at the L4-L5 and L5-S1 levels were obtained with the
      MLT (index test) and real-time ultrasound imaging (reference standard). METHODS:
      The inter-rater reliability of the MLT was examined by measuring the level of
      agreement between two blinded examiners. Concurrent validity of the MLT was
      investigated by comparing clinicians' judgments with real-time ultrasound imaging
      measures of lumbar multifidus function. RESULTS: Inter-rater reliability of the
      MLT was substantial to excellent (kappa=0.75 to 0.81, p<=.01) and free from
      errors of bias and prevalence. When performed at L4-L5 or L5-S1, the MLT
      demonstrated evidence of concurrent validity through its relationship with the
      reference standard results at L4-L5 (rbis=0.59-0.73, p<=.01). The MLT generally
      failed to demonstrate a relationship with the reference standard results from the
      L5-S1 level. CONCLUSIONS: Our results provide preliminary evidence supporting the
      reliability and validity of the MLT to assess lumbar multifidus function at the
      L4-L5 spinal level. Additional research examining the measurement properties and
      utility of this test should be undertaken before confident implementation with
      patients.

PMID- 24314769
TI  - Urea: a comprehensive review of the clinical literature.
AB  - INTRODUCTION: Urea is an organic compound that has been used clinically for
      dermatological diseases for more than a century. Urea is a potent emollient and
      keratolytic agent, making urea an effective monotherapy for conditions associated
      with dry and scaly skin. A systematic review of the literature is needed to
      provide clinicians with evidence-based applications of urea in the treatment of
      dermatological diseases. METHODS: A PubMed search was conducted using the term
      "urea" combined with "skin," "ichthyosis," "psoriasis," "xerosis," "emollient,"
      "onychomycosis," "dermatitis," and "avulsion." A total of 81 publications met
      inclusion criteria and were evaluated. Treatment indication(s), test agents,
      number of subjects, treatment protocols, results, and side effects were recorded.
      RESULTS: Effective treatment with urea has been reported for the following
      conditions: ichthyosis, xerosis, atopic dermatitis/eczema, contact dermatitis,
      radiation induced dermatitis, psoriasis/seborrheic dermatitis, onychomycosis,
      tinea pedis, keratosis, pruritus, and dystrophic nails. Furthermore, urea has
      been used with other medications as a penetration enhancing agent. Mild
      irritation is the most common adverse event, proving urea to be a safe and
      tolerable topical drug without systemic toxicity. DISCUSSION/CONCLUSION: Urea is
      a safe, effective dermatologic therapy with wide-ranging clinical utility and
      minimal, non-systemic side effects. In order to optimize patient care,
      dermatologists should be well informed with regards to urea's indications and
      efficacy.

PMID- 24314770
TI  - Black spots in the returning traveler.
AB  - African tick bite fever (ATBF) is a rickettsial infection that should be
      considered as the cause of fever in travelers returning from endemic regions of
      sub-Saharan Africa or the Caribbean. Patients typically present with a flu-like
      syndrome and may demonstrate one or more cutaneous inoculation eschars as a
      diagnostic key. We present a case of ATBF in a pregnant woman following her trip
      to Swaziland. Her symptoms rapidly improved with institution of effective
      antimicrobial treatment with azithromycin and rifampin; she made a full recovery.

PMID- 24314771
TI  - Sporotrichoid chromomycosis.
AB  - Chromomycosis is a chronic fungal skin infection. It manifests frequently by
      warty or vegetative lesions in exposed areas, most often secondary to trauma. The
      diagnosis, nevertheless, is confirmed by the presence of fungi in the mycological
      examination. In fact, the treatment remains a challenge given its recalcitrant
      nature. 

PMID- 24314772
TI  - First reported case of cellulitis due to Cryptococcus gattii in lung
      transplantation recipient: a case report.
AB  - Cryptococcus gattii are closely related species of encapsulated yeast-like fungi
      involved in the etiology of cryptococcosis, especially in immunocompetent
      individuals. Dissemination with involvement of many organ systems is common. On
      the other hand, cellulitis in an immunossupressed patient caused by C. gattii is
      rare. We present a case of disseminated disease caused by Cryptococcus gattii in
      a lung transplant recipient who manifested cellulitis. The disease was also
      complicated by a lung carcinoma. We emphasize that cryptococcal cellulitis
      related to C. gattii in solid organ transplant (SOT) recipients should be
      considered in the differential diagnosis of acute bacterial skin infections. 

PMID- 24314773
TI  - Photo recall reaction following the use of vancomycin.
AB  - Drug-induced erythema in the distribution of prior sunburn is called photo
      recall. Although more commonly induced by chemotherapeutics, it has also been
      associated with antibiotics such as ampicillin, cephalosporin, and gentamicin.
      Vancomycin has not been previously reported as a causal agent. This case report
      describes photo recall in a fifty-three year old woman undergoing treatment with
      vancomycin for a MRSA infection of the spine. Her eruption followed a photo
      distributed pattern on the chest, shoulders, neck and face sparing areas
      previously protected by her bathing suit. Of note, she reported a similar
      eruption following vancomycin two years prior. 

PMID- 24314774
TI  - Malignancies with skin lesions mimicking keratoacanthoma.
AB  - A variety of tumors mimicking keratoacanthoma have been described. Herein we
      categorize metastases of visceral malignancies that can present with the
      appearance of a keratoacanthoma. 

PMID- 24314775
TI  - Stasis dermatitis as a complication of recurrent levofloxacin-associated
      bilateral leg edema.
AB  - INTRODUCTION: Several drugs have been associated with the development of
      peripheral edema. Leg edema can result in dermatitis of the lower extremities. We
      describe levofloxacin-induced peripheral leg edema, which progressed to stasis
      dermatitis. METHODS: A 76-year-old man with a history of esophageal
      adenocarcinoma was administered intravenous vancomycin and a combination of
      piperacillin and tazobactam by injection for treatment of aspiration pneumonia.
      Prior to discharge, the patient's antibiotic therapy was switched to oral
      levofloxacin. The patient developed drug-associated bilateral peripheral leg
      edema and stasis dermatitis. Both the dermatitis and leg edema resolved after
      withdrawal of levofloxacin and administration of topical corticosteroid therapy.
      The patient had a similar reaction to levofloxacin one year prior, which had
      subsided with discontinuation of the drug. RESULTS: Several medications have been
      documented to cause leg edema and secondary stasis dermatitis. The timing,
      recurrence, and resolution of edema and stasis dermatitis with respect to the
      administration and termination of levofloxacin suggest that the leg edema and
      stasis dermatitis occurred secondary to levofloxacin administration. DISCUSSIONS:
      Levofloxacin can be added to the list of drugs associated with the development of
      peripheral leg edema. Stasis dermatitis proceeded by lower extremity edema can be
      added to the list of adverse events associated with levofloxacin.

PMID- 24314776
TI  - Granuloma annulare mimicking multicentric reticulohistiocytosis.
AB  - We describe a patient with granuloma annulare (GA) who presented with firm
      periungual papules mimicking "coral beads", a characteristic sign of multicentric
      reticulohistiocytosis (MRH). We highlight the importance of distinguishing
      between GA and MRH because the prognoses differ significantly. 

PMID- 24314777
TI  - Disseminated cutaneous sporotrichosis.
AB  - The dimorphic fungus Sporothrix schenckii commonly causes localized cutaneous
      disease with lymphocutaneous distribution. However, disseminated sporotrichosis
      occurs predominantly in immunocompromised patients. We report a case of
      disseminated cutaneous sporotrichosis in a patient with newly diagnosed HIV with
      a CD4 count of 208. The patient presented with multiple cutaneous and
      subcutaneous nodules as well as fever and malaise. Tissue culture and skin biopsy
      confirmed the diagnosis of sporotrichosis. He was started on itraconazole 200mg
      twice a day with rapid resolution of fever along with cessation of the
      development of new lesions. 

PMID- 24314778
TI  - Secondary syphilis: a case mimicking erythema multiforme clinically and
      pathologically.
AB  - Secondary syphilis, the hematogenous spread of Treponema pallidum, usually occurs
      4-10 weeks after initial exposure. The skin is involved in 70% of cases, with
      maculopapular, vesiculobullous, and ulcerative morphologies possible at
      presentation, making the diagnosis of secondary syphilis challenging given its
      ability to mimic many other conditions. We present an atypical case of secondary
      syphilis that closely resembled erythema multiforme (EM) clinically and
      histologically. 

PMID- 24314779
TI  - Reactive angioendotheliomatosis associated with cyroglobulinemia in a marathon
      runner.
AB  - We report a case of a 65-year-old marathon runner who presented with painful
      plaques, which were worse in cold weather and progressed to ulceration. A punch
      biopsy revealed vascular endothelial hyperplasia and an appearance consistent
      with reactive angioendotheliomatosis (RAE), a rare, but benign disorder of the
      skin. Subsequent investigations resulted in the diagnosis of type I
      cryoglobulinemia; the lesions resolved completely following treatment of the
      underlying disorder with lenalidomide. 

PMID- 24314780
TI  - Recurrent migratory angioedema as cutaneous manifestation in a familiar case of
      TRAPS: dramatic response to Anakinra.
AB  - BACKGROUND: Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS)
      is a hereditary autoinflammatory syndrome characterized by recurrent episodes of
      fever and localized inflammation. Clinical presentation can be very variable in
      terms of duration of fever attacks, periodicity, and accompanying manifestations.
      One of the most characteristic symptoms is the occurrence of migrating skin rash
      with myalgia that is sustained by monocytic inflammation. OBSERVATIONS: We herein
      present the case of a family suffering from TRAPS who had been misdiagnosed for a
      long period of time and whose main symptom was migrating angioedema. Skin biopsy
      from one of the patients documented a monocytic panniculitis. All the living
      patients responded dramatically to anakinra treatment. CONCLUSIONS: The classic
      symptom of migratory angioedema with myalgia in TRAPS can be produced by
      monocytic panniculitis.This manifestation is so characteristic of TRAPS that its
      occurrence, even in the absence of other manifestations, should prompt genetic
      analysis. Our patient's condition responded promptly to anakinra treatment.

PMID- 24314781
TI  - Facial actinic lichen nitidus successfully treated with hydroxychloroquin: a case
      report.
AB  - INTRODUCTION: Lichen nitidus is an unusual condition with chronic evolution. It
      arises as multiple tiny, shiny papules with a flat surface. Many clinical
      variants have been reported. We describe a new case of facial actinic lichen
      nitidus. Our patient responded rapidly to corticosteroids and hydroxychloroquine.
      CASE REPORT: A 23-year-old woman with photodistributed eruptions recurring during
      the summer with improvement during the winter presented to our institution.
      Clinical exam revealed pinhead sized flat and flesh-colored papules on her face.
      Koebner phenomenon was not observed. Palms, soles, nails, and mucosa were normal.
      Histologic examination of a cutaneous biopsy showed a well circumscribed
      lymphohistiocytic infiltrate in the papillary dermis in a "claw clutching a ball"
      pattern suggestive of lichen nitidus. The diagnosis of actinic lichen nitidus was
      made. Treatment included photoprotection, topical corticosteroids once daily for
      6 weeks, and hydroxychloroquine for 6 months. Remission of lesions was obtained
      after 4 weeks. CONCLUSION: Actinic lichen nitidus is rare. The true prevalence of
      this disease and the effectiveness of its various therapies is difficult to
      evaluate because it is usually asymptomatic and resolves without squelae.

PMID- 24314782
TI  - An atypical case of cutaneous leishmaniasis caused by Leishmania infantum in
      Portugal.
AB  - Leishmaniasis is a parasitic disease caused by an intracellular protozoan that
      belongs to the genus Leishmania and is transmitted by a phlebotomine sandfly. In
      Southwest Europe, including Portugal, cutaneous leishmaniasis is considered a
      rare disease of unknown or underestimated prevalence. Leishmania infantum is the
      only species identified as responsible for the autochthonous cases.We report the
      case of a 66-year-old man with an erythematous, painless plaque on the mid face
      region, accompanied by nasal obstruction with 9 months of evolution. The initial
      diagnoses were: lymphoma, subcutaneous mycosis, Wegener's granulomatosis, and
      lupus vulgaris. The diagnosis of leishmaniasis was based on histopathology
      findings and identification of L. infantum by DNA based methods. Blood cultures,
      abdominal ultrasound and myelogram ruled out systemic involvement. The patient
      was treated with intravenous meglumine antimoniate (20 mg per kg/day) for four
      weeks, without major side effects.We emphasize the importance of this case
      because human cutaneous leishmaniasis has rarely been diagnosed in Portugal and
      some cases are atypical, such as the situation herein described. 

PMID- 24314783
TI  - [Cutaneous infiltratiton by chronic myelononocytic leukemia: presentation of
      three cases].
AB  - Leukemia cutis refers to cutaneous infiltration by malignant hematopoietic cells.
      Its clinical manifestations are highly variable and biopsy is required for
      confirmation. We present three cases of patients with persistent monocytosis and
      skin lesions whose diagnosis was chronic myelomonocytic leukemia. The biopsy of
      skin lesions showed a dermal infiltration by atypical myelocytes and monocytes.
      Immunohistochemical study was positive for CD68. These findings were compatible
      with cutaneous infiltration by chronic myelomonocytic leukemic cells. 

PMID- 24314784
TI  - Cutaneous angiosarcoma clinically presenting as progressive solid facial edema in
      a 43-year-old male.
AB  - Cutaneous angiosarcoma of the head and neck is a rare, highly malignant neoplasm;
      prognosis is heavily influenced by tumor size, resectability, and stage at
      initial diagnosis. Most patients present with one to several erythematous to
      violaceous patches, plaques, or nodules. However, the clinical presentation is
      highly variable and leads to delayed diagnosis. We report cutaneous angiosarcoma
      in a 43-year-old man who presented with an 11-month history of progressive solid
      (non-pitting) edema involving his entire face, scalp, eyelids, and neck without
      characteristic clinical features of cutaneous angiosarcoma. A skin biopsy had
      shown non-specific findings consistent with solid facial edema or rosacea.
      Various etiologies were considered but there was no significant improvement after
      directed medical therapy. Repeat skin biopsies revealed angiosarcoma involving
      the dermis and sub-cutis. Computed tomography (CT) of the chest showed multiple
      lung nodules bilaterally and a lytic lesion in the T6 vertebra consistent with
      metastases. He was treated with single agent chemotherapy (paclitaxel), and had a
      partial response that restored his ability to open both eyes spontaneously;
      However, his edema has recently progressed 7 months after diagnosis. This is a
      rare example of cutaneous angiosarcoma presenting as progressive solid facial
      edema, which underscores the diverse range of clinical manifestations associated
      with this neoplasm. 

PMID- 24314785
TI  - Treatment of hidradenitis supprurativa associated pain with nonsteroidal anti
      inflammatory drugs, acetaminophen, celecoxib, gabapentin, pegabalin, duloxetine,
      and venlafaxine.
AB  - Hidradenitis Supprurativa is a painful dermatological condition. Although the
      pain of HS has unique aspects, the pain of HS pain shares common elements with
      essential pain, fibromyalgia, and pure neuropathic pain syndromes. Futhermore,
      depression plays an important role in the pain of HS. This paper reviews the
      potential for use of nonsteroidal anti-inflammatory drug (NSAIDS), acetaminophen,
      celecoxib, gabpentin, pregabalin, and the serotonin and norepinephrine reuptake
      inhibitors (SNRIs), duloxetine and venlafaxine, for treating HS related pain. No
      studies exist for pain control in HS. Initially, the pain of HS is treated
      medically e.g. oral rifampin and clindamycin or adalimumab to decrease
      inflammation, but an analysis of pain medications to treat the pain of HS merits
      its own discussion and treatment algorithm. First-line HS pain treatments
      include: topical analgesics and oral NSAIDs, such as celecoxib (Celebrex(r)), and
      acetaminophen. If these are inadequate, which is common, the less expensive
      gabapentin (Neurontin(r)) 400-1200 mg TID or the more expensive (Lyrica(r))
      pregabalin 50-100mg BID can be added for synergistic effect. In my experience, HS
      patients prefer pregabalin, which induces less drowiness than gabapentin. If
      these combinations are inadequate, an SNRI can be added. Of SNRIs, duloxetine
      (Cymbalta(r)) 30-120 mg, given QD or divided BID, is most optimal. I have used
      gabapetin or pregabalin in combination with duloxtine effectively. Venlafaxine
      (Effexor(r)), 75 mg-375mg (divided into BID or TID dosing), or in extended
      release form Venlafaxine ER (Effexor ER(r)) (37.5mg-375mg daily) can be combined
      with pregalin or gabapetin. Venlafaxine's cardiovascular side effects and lesser
      effectiveness serves HS patients less well then duloxetine, in my experience. An
      advantage of duloxetine and venlafaxine is that they can be used to treat the
      depression often associated with HS. If prolonged use of opiates is required,
      patients should be referred to a pain specialist. 

PMID- 24314788
TI  - Endoscopic ultrasound is inadequate to determine which T1/T2 esophageal tumors
      are candidates for endoluminal therapies.
AB  - OBJECTIVES: Esophageal endoscopic ultrasound is now regarded as essential in the
      staging of esophageal carcinoma. There is an increasing trend toward endoluminal
      therapies (ie, endoscopic mucosal resection and radiofrequency ablation) for pre
      cancer or early-stage cancers because of concerns of high morbidity associated
      with esophagectomy. This study reviews our institutional experience with
      preoperative endoscopic ultrasound staging of early esophageal cancers in
      patients who underwent an esophagectomy to evaluate the accuracy of staging by
      endoscopic ultrasound and how this affects treatment recommendations. METHODS: A
      prospective esophagectomy database of all patients undergoing an esophagectomy
      for esophageal cancer at a single high-volume institution was retrospectively
      reviewed for patients with early-stage esophageal cancer. This study analyzed
      patients with clinical Tis to T1 disease, as predicted by preoperative endoscopic
      ultrasound, and correlated this with the pathologic stages after esophagectomy.
      The surgical outcomes were evaluated to assess the safety of esophagectomy as a
      treatment modality. RESULTS: From 2005 to 2011, 107 patients (93 male, 14 female)
      with a mean age of 66 years (range, 39-91 years) were staged by preoperative
      endoscopic ultrasound to have esophageal high-grade dysplasia, carcinoma in situ,
      or T1 cancer and underwent an esophagectomy. Tumor depth was correctly staged by
      endoscopic ultrasound in only 39% (23/59) of pT1a tumors (invading into the
      lamina propria or muscularis mucosa) and 51% (18/35) of pT1b tumors (submucosal).
      Of the endoscopic ultrasound-staged cT1a-lpN0 lesions, there were positive lymph
      nodes in 15% of pathologic specimens (2/13). Patients with pT1a-mm lesions had a
      9% rate of pathologic lymph node involvement (1/11), and those with pT1b tumors
      had a 17% rate of lymph node spread (6/35). Esophagectomy was performed in all
      107 patients with a 30-day mortality rate of less than 1% (1/107). CONCLUSIONS:
      The sensitivity and specificity of endoscopic ultrasound for determining true
      pathologic staging are poor for early-stage esophageal cancers. Lesions thought
      to be cT1a-lpN0 by endoscopic ultrasound have at least pN1 disease in 15% of
      cases. Endoluminal therapy of these lesions based on endoscopic ultrasound
      undertreats a significant number of patients. Esophagectomy is still the standard
      therapy for early-stage esophageal cancers in the majority of patients.

PMID- 24314789
TI  - Evolving strategies for preserving the pulmonary valve during early repair of
      tetralogy of Fallot: mid-term results.
AB  - BACKGROUND: The aim of the study was to evaluate our results with pulmonary valve
      (PV) preservation in selected patients with tetralogy of Fallot (TOF). METHODS:
      From January 2007, 69 patients who underwent early transatrial TOF repair were
      enrolled in the study. The patients were divided into 2 groups: PV preservation
      by PV annulus balloon dilation (group 1) and PV cusp reconstruction after annular
      incision (group 2). RESULTS: Thirty-four patients underwent a successful PV
      annular preservation (49%). Median age at surgery was 113 days (range, 36-521
      days) (group-1 vs group-2, P = not significant). Median preoperative PV Z score
      was -3.15 (range, -0.95 to -5.62) (group-1 vs group-2, P = .03). Median intensive
      care unit and hospital stays were 3 and 10 days, respectively (group 1 vs group
      2, P = not significant). Median follow-up time was 580 days (range, 189-1940
      days) (group 1 vs group 2, P = .08). Two patients were reoperated for residual
      right ventricular outflow tract (RVOT) obstruction (1 in group 1 and 1 in group
      2). The remaining patients are alive and well. Median peak RVOT gradient was 25
      mm Hg (range, 8-60 mm Hg) (group 1 vs group 2, P = not significant). The degree
      of PV regurgitation in group 1 was none/mild in 24 patients (80%) and moderate in
      6 (20%) and was none/mild in 8 patients (25%), moderate in 11 (34.4%), and severe
      in 13 (28.6%) in group 2 (P = .001). Median right ventricular fractional area
      change was 55% (range, 42%-70%) in group 1 and 50% (range, 40%-63%) in group 2 (P
      = .003). CONCLUSIONS: The integrity and function of the PV can be preserved in
      selected patients during early repair of TOF by concomitant balloon dilation,
      leading to a better mid-term right ventricular function.

PMID- 24314790
TI  - [Integrative medicine in the management of functional dyspepsia. Role of the
      herbal preparation STW5].
AB  - Functional dyspepsia is defined as a group of symptoms, whether related or
      unrelated to intake, localized in the upper abdomen, that manifest in the form of
      discomfort or epigastric pain, postprandial fullness and early satiety, in the
      absence of any demonstrable organic or structural anomaly. The etiopathogenesis
      and physiopathology of the process are unknown but factors that may be involved
      include gastric motility disorders, visceral hypersensitivity, psychological and
      genetic factors, Helicobacter pylori infection, and gastric acid hypersecretion.
      There is still no etiological treatment and consequently treatment is empirical
      and based on symptoms. This article reviews the main therapeutic options
      currently available, with special emphasis on the use of certain phytoceuticals
      (STW 5), in an attempt to integrate with traditional scientific medicine. This
      article also proposes an integrative therapeutic algorithm. 

PMID- 24314791
TI  - [Bulbar duodenal adenocarcinoma. An unsuspected diagnosis].

PMID- 24314792
TI  - [Mesenteric panniculitis as a cause of chronic abdominal pain].

PMID- 24314793
TI  - [Cutaneous metastasis from a pancreatic adenocarcinoma as a form of presentation
      of tumoral recurrence].

PMID- 24314794
TI  - [Pericardial schwannoma. Echoendoscopy as an aid in the study of cardiac
      lesions].

PMID- 24314795
TI  - [Aeromonas hydrophila colitis as the initial presentation of colon cancer].

PMID- 24314796
TI  - Imaging of dizziness.
AB  - Dizziness is a frequent indication for neuroimaging within the outpatient and
      emergency setting with variable diagnostic yield. The majority of persistent,
      recurrent, and isolated dizziness can be managed clinically. However, it may be
      difficult to distinguish a benign peripheral aetiology from a central cause,
      particularly in the emergency setting. We review the relevant anatomy,
      differential diagnosis, and key imaging features of central and peripheral causes
      of dizziness, as well as the literature for the diagnostic yield in acute and
      outpatient settings.

PMID- 24314797
TI  - [Case management and complex chronic diseases: concepts, models, evidence and
      uncertainties].
AB  - Chronic diseases are the greatest challenge for Health Care, but the conventional
      health care models have failed noticeably. Nurses are one of the main providers
      of the services developed to tackle this challenge, with special emphasis on case
      management, as one of the most common forms. But, one of the key problems is that
      case management is poorly conceptualized, and with the diversity of experience
      available, make its development and comparative evaluation difficult. An in-depth
      review on case management definition and concepts is presented in this article,
      with a description of the models, ingredients and the effectiveness reported in
      various studies. The remaining uncertainties in case management, such as the
      heterogeneity of designs and target populations, the weak description of the
      components, and the scarce use of research models for complex interventions, are
      also discussed. Finally, some key factors for a successful implementation of case
      management are detailed, such as a clear definition of accountability and roles,
      the existence of support to guarantee the competence of case managers, the use of
      valid mechanisms for case finding, adjusted caseload, accessible and team-shared
      record systems, or the integration of health and social services. 

PMID- 24314798
TI  - Explanations for violent behaviour--an interview study among forensic in
      patients.
AB  - The alleged relation between mental disorder and violent criminal behaviour has
      been investigated mainly from an epidemiological perspective. Population-based
      registry studies have shown that violence occurs more frequently among people
      with mental disorders, like schizophrenia and bipolar disorder, compared with
      control subjects, but that the increased risk is largely mediated by drug abuse
      and socio-economic deprivation. The aim of this study was to explore how patients
      who have committed violent or sexual crimes and have been sentenced to forensic
      psychiatric care by a Swedish court of law construed their criminal actions in
      terms of causes. Forty-six participants from six different Swedish forensic
      psychiatric clinics were included in the study. A semi-structured interview study
      was conducted and the data was analysed using a thematic analysis. A large group
      of the participants did not believe that the mental disorder played any role in
      the criminal events. Contributing causes that were mentioned were drug abuse and
      social factors. 

PMID- 24314799
TI  - The effect of episiotomy on pelvic organ prolapse assessed by pelvic organ
      prolapse quantification system.
AB  - OBJECTIVE: This study aimed to assess the association between episiotomy and
      measures of pelvic organ prolapse quantification system (POP-Q) in a cohort of
      women with vaginal parturition. STUDY DESIGN: A prospective study was conducted
      with 549 eligible patients with vaginal delivery history. Women who were
      pregnant, gave birth within the preceding 6 months period, had a known history of
      pre-pregnant prolapse, had a history of hysterectomy or any operation performed
      for pelvic organ prolapsus and stress urinary incontinence, refused to
      participate and to whom POP-Q examination could not be performed (due to anatomic
      or orthopedic problems) were excluded. Patients were categorized as women with
      episiotomy and without episiotomy. The degree of genital prolapse was assessed by
      using POP-Q system. The effect of episiotomy on overall POP-Q stage and
      individual POP-Q points was calculated with logistic regression. RESULTS: 439
      patients had a history of episiotomy whereas 110 patients had no episiotomy.
      38.2% of women without an episiotomy, and 32.0% of women with episiotomy had
      genital prolapse determined by POP-Q system. There was no statistically
      significant association between episiotomy and POP-Q stage (AOR, -0.24; 95% CI, 
      0.65-0.18, P=0.26). Episiotomy was found among the independent predictors for
      certain POP-Q points such as Bp, perineal body (pb) and total vaginal length
      (tvl). Episiotomy was negatively correlated with prolapse of Bp and with pb and
      tvl. CONCLUSION: Episiotomy had an effect on certain POP-Q indices, but had no
      influence on overall POP-Q stage.

PMID- 24314800
TI  - Cystocele recurrence after anterior colporrhaphy with and without mesh use.
AB  - OBJECTIVE: Mesh reinforcement in cystocele repair has become popular in recent
      years, with some evidence of reduced recurrence rates. In this retrospective
      cohort series, we aimed to assess subjective and objective outcomes, including
      ultrasound quantification of prolapse, following anterior colporrhaphy with and
      without mesh use for anterior compartment prolapse. STUDY DESIGN: We assessed
      anatomical and functional outcomes of patients after cystocele repair in three
      tertiary urogynecology units. Outcome measures included either objective prolapse
      recurrence (defined as cystocele>=Stage 2 ICS POP-Q or bladder descent >=10mm
      below the symphysis pubis on ultrasound) or subjective prolapse recurrence
      (defined as symptoms of vaginal lump, bulge or dragging sensation post
      operatively). Comparisons between mesh use and anterior colporrhaphy-only groups
      were undertaken, adjusting for potential confounders (age, BMI, vaginal parity,
      previous prolapse repair, levator avulsion and length of follow-up) using
      multiple linear regression and logistic regression methods. RESULTS: 183 patients
      were assessed at an average follow-up of 4 years. Eight-three patients had
      anterior colporrhaphy between January 2002 and December 2005, and 100 had an
      anterior mesh repair between March 2004 and October 2008. Forty-six (55%)
      patients in the anterior colporrhaphy group compared to 33 (33%) in the mesh use
      group were diagnosed with a recurrent cystocele (>=stage 2) (p=0.002). After
      adjustment for age, BMI, previous vaginal delivery, previous vaginal repair
      surgery, and length of follow-up, the benefit of mesh on prolapse recurrence was
      principally experienced by women with major levator trauma. CONCLUSIONS: At a
      mean of four years' follow-up, mesh augmentation was associated with reduced
      cystocele recurrence, but this effect was limited to patients with levator
      avulsion.

PMID- 24314802
TI  - Pathogens. Foreword.

PMID- 24314801
TI  - A comparison of outcomes from in vitro fertilization cycles stimulated with
      either recombinant luteinizing hormone (LH) or human chorionic gonadotropin
      acting as an LH analogue delivered as human menopausal gonadotropins, in subjects
      with good or poor ovarian reserve: a retrospective analysis.
AB  - OBJECTIVES: To compare rates of pregnancy and IVF parameters in subjects who were
      stimulated with FSH plus recombinant human luteinizing hormone or menopausal
      gonadotropins. To determine whether responses to type of LH differ in poor or
      good responders. STUDY DESIGN: Retrospective analysis at a university-based
      fertility center. Subjects were women with good and poor ovarian reserve, who
      underwent in vitro fertilization during a 2 year period, as part of a long
      agonist (N=122), or microdose flair (N=79) protocol. Measurements included FSH
      and LH dose, number of oocytes collected, number of embryos obtained, and
      pregnancy and clinical pregnancy rates. RESULTS: Patients treated with r-hLH
      (n=105) had higher numbers of eggs retrieved and of embryos while using less FSH
      than their hMG-treated (n=96) counterparts. Pregnancy and clinical pregnancy
      rates were significantly higher with r-hLH than with hMG protocols (p=0.008 and
      0.009, respectively). If patients had a baseline serum FSH level >=10IU/L,
      clinical pregnancy rates were higher when r-hLH was used. When the antral
      follicle count was below 6 no significant differences in stimulation parameters
      or outcomes were detected between the groups. CONCLUSION: r-hLH may be beneficial
      when compared to hMG and used for in-vitro fertilization, except in subjects with
      baseline follicle counts less than 6. Further data should be obtained.

PMID- 24314803
TI  - Viral hemorrhagic fever viruses.

PMID- 24314804
TI  - Global infectious diseases - the new norm for the United States?

PMID- 24314805
TI  - Travel-related illness.

PMID- 24314806
TI  - Update - pathogens of concern.

PMID- 24314807
TI  - Mycobacterium chelonae.

PMID- 24314808
TI  - Malaria (Plasmodium).

PMID- 24314809
TI  - Measles.

PMID- 24314810
TI  - Polio.

PMID- 24314811
TI  - Conclusion.

PMID- 24314812
TI  - Walker 256/B malignant breast cancer cells disrupt osteoclast cytomorphometry and
      activity in rats: modulation by alpha-tocopherol acetate.
AB  - We examined the effects of vitamin E supplementation (VES) on osteoclast (OC)
      resorbing activity and cytomorphometry in Walker 256/B tumor osteolytic rats.
      Twenty-four aged male rats were randomized into 3 groups: 6 were sham operated; 9
      were injected in the right hind limb with Walker 256/B cells (W256 group); and 9
      were injected as above and supplemented with VE (45mg/kg BW) (W256VE group).
      Twenty days later, bone mass (BV/TV) and some microarchitectural parameters were
      assessed. Some histodynamic parameters, cellular and nuclear form factors (FFC
      and FFN), and nuclear-cytoplasmic ratio (N/C) of OC were measured for each group.
      W256 group exhibited osteolytic lesions in the operated femora. Walker 256/B
      induced trabecular perforation and decreased BV/TV associated with significant
      increases in OC numbering (N.Oc/B.Ar and Oc.N/B.Pm) and activity (ES/BS and
      Oc.S/BS). While FFN remain unchanged, the FFC and N/C ratio increased in the W256
      group. W256VE showed less osteolytic lesions. Moreover, disruption of bone
      microarchitecture and OC activity in W256VE group decreased. VES reduced the
      malignant Walker 256/B-induced enhanced OC resorbing activity with cytoinhibition
      rate reaching 41%. The protective effect of VE may be due to its modulation of OC
      cytomorphometry and subsequently their activity. 

PMID- 24314813
TI  - What is the effect of compression garments on a balance task in female athletes?
AB  - OBJECTIVES: To investigate the effect of long leg compression garments on the
      postural sway and balance ability of female athletes at a state sports institute.
      DESIGN: A laboratory was set up to analyse kinetic and kinematic variables using
      a double blind, randomised controlled repeated measures cross over design.
      METHOD: Participants were required to perform a single leg balance task for up to
      60s across six conditions; including eyes-open and eyes-closed while wearing
      conventional shorts (control), loose-fitted compression garment and well-fitted
      compression garments. Simultaneous measurements of ground reaction forces and
      full body joint kinematics were recorded. Postural stability was assessed by
      measuring the overall stabilisation time as well as the movement of the centre of
      pressure (CoP) and centre of mass (CoM) from baseline measures. RESULTS: During
      one leg stance, significantly greater postural stability (p < 0.01) was observed
      with eyes open vs eyes closed, irrespective of compression group. A significantly
      greater (p < 0.05) balance time was observed with eyes closed when wearing well
      fitted compression garments compared to conventional shorts. Differences were not
      present with use of the loose-fitted garment. Additionally, a significant
      interaction effect between compression condition and vision was observed
      analysing the variation about the sway (swaySD) of the CoP and CoM data (p <
      0.05). The interaction effect revealed greater variability of movement with eyes
      closed as participants' level of compression decreased. No significant
      differences were observed with eyes open. CONCLUSIONS: The difficulties of
      postural stability while maintaining the single leg stance wearing conventional
      shorts were improved with use of the well-fitted compression garments (in the
      eyes-closed condition). Proper fitted compression garments may be beneficial for
      injury management and injury prevention.

PMID- 24314814
TI  - Gluteus minimus: an intramuscular EMG investigation of anterior and posterior
      segments during gait.
AB  - Gluteus minimus is believed to consist of two structurally and functionally
      unique segments (anterior and posterior); however there is a lack of
      electromyography (EMG) research that attempts to verify current theoretical
      knowledge of this muscle. The purpose of this study was therefore to evaluate the
      function of gluteus minimus during gait, and to determine whether anterior and
      posterior segments are functionally independent. Bipolar fine wire intramuscular
      EMG electrodes were inserted into anterior and posterior gluteus minimus segments
      of fifteen healthy volunteers (9 males) according to previously verified
      guidelines. Participants completed a series of four walking trials, followed by
      maximum voluntary isometric contractions in five different positions. Temporal
      and amplitude variables for each segment were compared across the gait cycle with
      independent t-tests. The relative contribution of each segment to the maximum
      resisted trials was compared with Mann-Whitney U tests (alpha = 0.05). Anterior
      and posterior segments were contracting at different relative intensities for
      three of the five maximum resisted trials (effect size = 0.39 to 0.62, P <
      0.037). The posterior segment was larger in EMG amplitude (peak and average)
      during the first 20% of the gait cycle (effect size = 0.96 to 1.03, P < 0.02),
      while the anterior segment peaked later in the stance phase (effect size = 0.83,
      P = 0.034). Gluteus minimus is therefore composed of functionally independent
      segments. These results build on contemporary theoretical knowledge and may
      signify hip stabilising roles for each segment across different phases of the
      gait cycle.

PMID- 24314815
TI  - Radiotherapy for the treatment of pain in malignant pleural mesothelioma: a
      systematic review.
AB  - Radiotherapy is commonly used to treat pain in malignant pleural mesothelioma
      (MPM). The purpose of this systematic review is to examine the evidence for this
      practice. Medline (1946-2013), Embase (1974-2013) and Central (The Cochrane
      Library Issue 9, 2012) databases were searched. Eligible studies met the
      following criteria: MPM (histological or radiological diagnosis), radiotherapy
      given with the intent of improving pain, response rates to radiotherapy reported,
      dose and fractionation reported and the relationship between radiotherapy and
      pain response explored. All studies had independent review and were graded
      according to evidence level. Eight studies met the eligibility criteria. Two
      studies were prospective single arm phase II studies while the remainder were
      retrospective case series. All were graded as either Level 2 or Level 3 evidence.
      Due to marked heterogeneity among studies, quantitative synthesis of results was
      not possible. No high quality evidence currently exists to support radiotherapy
      in treating pain in MPM. Studies focusing on clear pain endpoints and improving
      target delineation are needed. Such studies should also use modern radiotherapy
      techniques and concentrate on dose escalation. 

PMID- 24314816
TI  - [Streptococcus suis acute meningitis].

PMID- 24314817
TI  - Isolated preputial reconstruction in distal hypospadias.
AB  - OBJECTIVE: The aim of this single centre study was to determine: a) the outcome
      of isolated preputial reconstruction in distal hypospadias and b) overall
      parental satisfaction. METHODS: A retrospective analysis of case notes was
      performed to determine outcome. Postal parent-satisfaction questionnaires were
      devised to quantify subjective assessment of care and outcome. RESULTS: A total
      of 33 cases of isolated preputial reconstruction were identified between 2006 and
      2012. Three sets of notes were untraceable. The median age of the 30 remaining
      patients at surgery was 23 months (range 11-119). At follow-up, 28 (94%) patients
      had retractile foreskins that had healed well. One patient (3%) had a foreskin
      fistula and the parents chose to proceed with circumcision rather than fistula
      closure. A second patient (3%) developed late phimosis secondary to balanitis
      xerotica obliterans and also underwent circumcision. Twelve follow-up
      questionnaires were returned. The median overall success rating of the operation
      was 4.7/5.0 (94%). All respondents reported that they would recommend the
      procedure to another parent whose child has a similar diagnosis. CONCLUSION:
      Isolated preputial reconstruction improves the cosmetic appearances in distal
      hypospadias, has a low complication rate and offers high parental satisfaction.

PMID- 24314818
TI  - Role of endoscopic treatment of vesico-ureteric reflux in downgrading renin
      angiotensin system activation.
AB  - OBJECTIVES: The objective of this study was to assess the role of endoscopic
      treatment of vesico-ureteric reflux (VUR) in downgrading renin angiotensin system
      (RAS) activation. METHODS: Of 115 patients diagnosed and treated for VUR, 63
      underwent hyaluronic acid/dextranomer (deflux) injection in a total of 99
      ureteric moieties. Patients were monitored for urinary tract infection (UTI),
      glomerular filtration rate (GFR), plasma renin activity (PRA), renal scarring,
      persistence, or appearance of contra-lateral reflux. RESULTS: Grade III VUR was
      most common (38%), and the most common cause of VUR was primary (60%). Analysis
      of patient characteristics at presentation revealed increased PRA in most cases
      (68%). Grade I VUR showed the most avid decrease in serum PRA levels after single
      injection. Serum PRA levels were sustainably low in patients of grade I and II
      VUR, whereas in patients of grade III values kept rising after reaching nadir.
      This increase in PRA levels correlated well with persistence of symptoms and
      reappearance of VUR in some patients. CONCLUSION: PRA levels can be used as an
      indicator to initiate treatment of VUR. They can also be used for monitoring the
      progress of the disease and efficacy of the treatment given.

PMID- 24314819
TI  - Impact of internal spermatic artery preservation during laparoscopic
      varicocelectomy on recurrence and the catch-up growth rate in adolescents.
AB  - OBJECTIVE: To investigate the effectiveness of laparoscopic varicocelectomy (LV)
      in adolescents with varicocele and analyze the impact of internal spermatic
      artery (ISA) preservation on surgical outcomes. MATERIALS AND METHODS: Data on 92
      adolescents with left varicocele who underwent LV between December 1998 and
      January 2011 were retrospectively analyzed. The mean age of the patients was 13.2
      +/- 2.1 years. Age, grade of disease, number of ligation veins, recurrence rates,
      and catch-up growth were analyzed in patients who underwent ISA preservation and
      ligation. The median duration of the follow-up was 21 months. RESULTS: ISA
      preservation was performed on 50 patients (54%). There were no significant inter
      group differences in terms of age, varicocele grade, number of ligation veins,
      and catch-up growth (93% vs. 90%). The patients who received artery preservation
      demonstrated a higher recurrence rate (22%) than those who received artery
      ligation (5%; p = 0.032). Among 13 patients who had persistent or recurrent
      varicocele, nine were treated with embolization and one was treated with
      magnification-assisted subinguinal varicocelectomy. None of these 10 patients
      demonstrated recurrence or testicular atrophy. CONCLUSIONS: LV with ISA ligation
      can reduce the recurrence rate and results in the same catch-up growth rate in
      comparison with LV with ISA preservation.

PMID- 24314820
TI  - Injury to the axillary nerve after reverse shoulder arthroplasty: an anatomical
      study.
AB  - BACKGROUND: Subclinical neurological lesions after reverse shoulder arthroplasty
      are frequent, mainly those involving the axillary nerve. One of the major
      reported risk factors is postoperative lengthening of the arm. The purpose of
      this study was to evaluate the anatomical relationship between the axillary nerve
      and prosthetic components after reverse shoulder arthroplasty. The study
      hypothesis was that inferior overhang of the glenosphere relative to glenoid
      could put this nerve at risk. MATERIAL AND METHODS: Eleven fresh frozen shoulder
      specimens were dissected after having undergone reverse shoulder arthroplasty
      using a classic deltopectoral approach. RESULTS: The mean distance from the
      inferior border of the glenoid to the inferior edge of the glenosphere was 6.0+/
      4.3mm (range, 1.0 to 16.2mm). The axillary nerve was never closer than 15mm to
      the glenosphere. The main anterior branch of the axillary nerve was in close
      contact with the posterior metaphysis or humeral prosthetic implant. The mean
      distance between the nerve and the humeral implants was 5.2+/-2.1mm (range, 2.0
      to 8.1mm). CONCLUSIONS: The proximity of the axillary nerve to the posterior
      metaphysis or humeral implants may be a risk factor for axillary nerve injury
      after reverse shoulder arthroplasty. CLINICAL RELEVANCE: This study quantifies
      the proximity of the axillary nerve to the implant after reverse shoulder
      arthroplasty. LEVEL OF EVIDENCE: Basic science study, cadaver study.

PMID- 24314821
TI  - Author reply: To PMID 24314834.

PMID- 24314822
TI  - Commentary on "The influence of lung airways branching structure and diffusion
      time on measurements and models of short-range 3He gas MR diffusion".
AB  - In a recently published paper by Parra-Robles and Wild, the authors challenge the
      in vivo lung morphometry technique (based on hyperpolarized gas diffusion MRI)
      developed by our Washington University research group. In this Commentary we
      demonstrate that the main conclusion of Parra-Robles and Wild, that our MRI-based
      lung morphometry technique "produces inaccurate estimates of the airway
      dimensions", does not have any scientific basis and is not in agreement with the
      considerable body of peer-reviewed scientific reports as well as with Parra
      Robles and Wild's own data. On the contrary, our technique has a strong
      theoretical background, is validated, and provides accurate 3D tomographic
      information on lung microstructural parameters previously available only from
      invasive biopsy specimens. This technique has already produced a number of
      results related to lung morphology and function that were not previously
      available. In our Commentary we also discuss a number of other incorrect
      statements in and shortcomings of Parra-Robles and Wild's paper.

PMID- 24314823
TI  - Regadenoson-stress myocardial CT perfusion and single-photon emission CT:
      rationale, design, and acquisition methods of a prospective, multicenter,
      multivendor comparison.
AB  - Pharmacologic stress myocardial CT perfusion (CTP) has been reported to be a
      viable imaging modality for detection of myocardial ischemia compared with single
      photon emission CT (SPECT) in several single-center studies. However, regadenoson
      stress CTP has not previously been compared with SPECT in a multicenter,
      multivendor study. The rationale and design of a phase 2, randomized, cross-over
      study of regadenoson-stress myocardial perfusion imaging by CTP compared with
      SPECT are described herein. The study will be conducted at approximately 25 sites
      by using 6 different CT scanner models, including 64-, 128-, 256-, and 320-slice
      systems. Subjects with known/suspected coronary artery disease will be randomly
      assigned to 1 of 2 imaging procedure sequences; rest and regadenoson-stress SPECT
      on day 1, then regadenoson-stress CTP and rest CTP/coronary CT angiography (same
      acquisition) on day 2; or regadenoson-stress CTP and rest CTP/CT angiography on
      day 1, then rest and regadenoson-stress SPECT on day 2. The prespecified primary
      analysis examines the agreement rate between CTP and SPECT for detecting or
      excluding ischemia (>=2 or 0-1 reversible defects, respectively), as assessed by
      3 independent blinded readers for each modality. Non-inferiority will be
      indicated if the lower boundary of the 95% CI for the agreement rate is within
      0.15 of 0.78 (the observed agreement rate in the regadenoson pivotal trials). The
      protocol described herein will support the first evaluation of regadenoson-stress
      CTP by using multiple scanner types compared with SPECT. 

PMID- 24314825
TI  - The joint structure of normal and pathological personality: further evidence for
      a dimensional model.
AB  - OBJECTIVE: The literature proposes a joint structure of normal and pathological
      personality with higher-order factors mainly based on the five-factor model of
      personality (FFM). The purpose of the present study was to examine the joint
      structure of the FFM and the DSM-IV personality disorders (PDs) and to discuss
      this structure with regard to higher-order domains commonly reported in the
      literature. METHODS: We applied a canonical correlation analysis, a series of
      principal component analyses with oblique Promax rotation and a bi-factor
      analysis with Geomin rotation on 511 subjects of the general population of
      Zurich, Switzerland, using data from the ZInEP Epidemiology Survey. RESULTS: The
      5 FFM traits and the 10 DSM-IV PD dimensions shared 77% of total variance.
      Component extraction tests pointed towards a two- and three-component solution.
      The two-component solution comprised a first component with strong positive
      loadings on neuroticism and all 10 PD dimensions and a second component with
      strong negative loadings on extraversion and openness and positive loadings on
      schizoid and avoidant PDs. The three-component solution added a third component
      with strong positive loadings on conscientiousness and agreeableness and a
      negative loading on antisocial PD. The bi-factor model provided evidence for 1
      general personality dysfunction factor related to neuroticism and 5 group
      factors, although the interpretability of the latter was limited. CONCLUSIONS:
      Normal and pathological personality domains are not isomorphic or superposable,
      although they share a substantial proportion of variance. The two and three
      higher-order domains extracted in the present study correspond well to equivalent
      factor-solutions reported in the literature. Moreover, these superordinate
      factors can consistently be integrated within a hierarchical structure of
      alternative four- and five-factor models. The top of the hierarchy presumably
      constitutes a general personality dysfunction factor which is closely related to
      neuroticism.

PMID- 24314824
TI  - Baseline comprehensive geriatric assessment is associated with toxicity and
      survival in elderly metastatic breast cancer patients receiving single-agent
      chemotherapy: results from the OMEGA study of the Dutch breast cancer trialists'
      group.
AB  - AIM: To evaluate the association between baseline comprehensive geriatric
      assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly
      metastatic breast cancer (MBC) patients treated with first-line palliative
      chemotherapy. PATIENTS AND METHODS: MBC patients (>=65 years) were randomized
      between pegylated liposomal doxorubicine or capecitabine. CGA included
      instrumental activities of daily living (IADL), cognition using the mini-mental
      state examination (MMSE), mood using the geriatric depression scale (GDS),
      comorbidity using the Charlson index, polypharmacy and nutritional status using
      the body mass index. Frailty on CGA was defined as one or more of the following:
      IADL <= 13, MMSE <= 23, GDS >= 5, BMI <= 20, >=5 medications or Charlson >=2. The
      cut-off for frailty on the GFI was >=4. RESULTS: Of the randomized 78 patients
      (median age 75.5 years, range 65.8-86.8 years), 73 were evaluable for CGA; 52
      (71%) had one or more geriatric conditions. Grade 3-4 chemotherapy-related
      toxicity was experienced by 19% of patients without geriatric conditions compared
      to 56% of patients with two geriatric conditions and 80% of those with three or
      more (p = 0.002). Polypharmacy was the only individual factor significantly
      associated with toxicity (p = 0.001). GFI had a sensitivity of 69% and a
      specificity of 76% for frailty on CGA, and was not significantly associated with
      survival or toxicity. CONCLUSION: In this study of elderly patients with MBC, the
      number of geriatric conditions correlated with grade 3-4 chemotherapy-related
      toxicity. Therefore, in elderly patients for whom chemotherapy is being
      considered, a CGA could be a useful addition to the decision-making process.

PMID- 24314826
TI  - Salmonella enterica isolated from infections in Australian livestock remain
      susceptible to critical antimicrobials.
AB  - Salmonella enterica is a zoonotic pathogen causing a variety of diseases in
      humans and animals. Many countries are reporting an increase in the prevalence of
      multidrug-resistant (MDR) S. enterica in food animals. The aim of this study was
      to determine whether S. enterica isolated from livestock in New South Wales,
      Australia, have similar resistance traits to those reported internationally.
      Salmonella enterica (n=165) from clinical infections in food animals between 2007
      and 2011 were serotyped and tested for susceptibility to 18 antimicrobials. Also,
      22 antimicrobial resistance genes (ARGs), 3 integrons and 18 plasmid replicon
      types were screened for using PCR. Most isolates (66.1%) remained susceptible to
      all antimicrobials; 8.5% of the isolates were resistant to four or more
      antimicrobials. Antimicrobials with the highest prevalence of resistance were
      sulfafurazole (28.5%), ampicillin (17.0%), tetracycline (15.8%) and trimethoprim
      (8.5%). There was no resistance to fluoroquinolones or third-generation
      cephalosporins. The most common ARGs were blaTEM (15.2%), sul2 (10.3%), tetB
      (9.1%), tetA (5.5%), aphA1 (4.8%) and dhfrV (4.8%). Class 1 integrons (7.9%) and
      IncFIIA (69.7%) were the most commonly detected integron and plasmid replicon
      types, respectively. Class 1 integrons were positively associated with MDR
      phenotypes and ARG carriage (P<=0.001). Internationally prominent MDR serovars
      associated with severe disease in humans (e.g. AmpC-positive Salmonella Newport)
      were not detected. Overall, the comparatively favourable resistance status of S.
      enterica in Australian livestock represents minimal public health risk associated
      with MDR strains and supports a conservative approach to the registration of
      antimicrobial drug classes in food-producing animals. 

PMID- 24314827
TI  - European Association of Urology guidelines on priapism.
AB  - CONTEXT: Priapism is defined as a penile erection that persists beyond or is
      unrelated to sexual interest or stimulation. It can be classified into ischaemic
      (low flow), arterial (high flow), or stuttering (recurrent or intermittent).
      OBJECTIVE: To provide guidelines on the diagnosis and treatment of priapism.
      EVIDENCE ACQUISITION: Systematic literature search on the epidemiology,
      diagnosis, and treatment of priapism. Articles with highest evidence available
      were selected to form the basis of these recommendations. EVIDENCE SYNTHESIS:
      Ischaemic priapism is usually idiopathic and the most common form. Arterial
      priapism usually occurs after blunt perineal trauma. History is the mainstay of
      diagnosis and helps determine the pathogenesis. Laboratory testing is used to
      support clinical findings. Ischaemic priapism is an emergency condition.
      Intervention should start within 4-6h, including decompression of the corpora
      cavernosa by aspiration and intracavernous injection of sympathomimetic drugs
      (e.g. phenylephrine). Surgical treatment is recommended for failed conservative
      management, although the best procedure is unclear. Immediate implantation of a
      prosthesis should be considered for long-lasting priapism. Arterial priapism is
      not an emergency. Selective embolization is the suggested treatment modality and
      has high success rates. Stuttering priapism is poorly understood and the main
      therapeutic goal is the prevention of future episodes. This may be achieved
      pharmacologically, but data on efficacy are limited. CONCLUSIONS: These
      guidelines summarise current information on priapism. The extended version are
      available on the European Association of Urology Website
      (www.uroweb.org/guidelines/). PATIENT SUMMARY: Priapism is a persistent, often
      painful, penile erection lasting more than 4h unrelated to sexual stimulation. It
      is more common in patients with sickle cell disease. This article represents the
      shortened EAU priapism guidelines, based on a systematic literature review. Cases
      of priapism are classified into ischaemic (low flow), arterial (high flow), or
      stuttering (recurrent). Treatment for ischaemic priapism must be prompt in order
      to avoid the risk of permanent erectile dysfunction. This is not the case for
      arterial priapism.

PMID- 24314828
TI  - Epidemiological studies are important to trigger health care decisions.

PMID- 24314829
TI  - [Pulmonary CO/NO transfer: physiological basis, technical aspects and clinical
      impact].
AB  - Diseases affecting the alveolar-capillary membrane or the capillary blood vessels
      can impair pulmonary gas exchanges and lung diffusion. The single-breath transfer
      factor of the lung for carbon monoxide (TL,CO) is the classical technique for
      measuring gas transfer from the alveolus to the pulmonary capillary blood.
      Pulmonary gas exchanges can also be explored by the transfer factor of the lung
      for nitric oxide (TL,NO). TL,NO represents a better index for the diffusing
      capacity of the alveolar-capillary membrane whereas TL,CO is more influenced by
      red blood cell resistance. Membrane diffusing capacity (DM) and pulmonary
      capillary blood volume (Vc) derivated from TL,CO and TL,NO by the Roughton
      Forster equation can give additional insights into pulmonary pathologies. The
      clinical impact of the CO/NO transfer has still to be precised even if this
      measurement seems to provide an alternative way of investigating the alveolar
      membrane and the blood reacting with the gas. 

PMID- 24314830
TI  - Evaluating the quality and readability of thyroplasty information on the
      Internet.
AB  - OBJECTIVES/HYPOTHESIS: To assess the quality and readability of thyroplasty
      information available on the Internet. STUDY DESIGN: Cross-sectional study.
      METHODS: We conducted a Google search for "thyroplasty treatment" and analyzed
      the first 50 Web sites using the DISCERN instrument, the Flesch Reading Ease
      Score (FRES), and the Flesch-Kincaid Grade Level (FKGL) score. DISCERN is a 16
      item validated questionnaire used to assess the quality of written health
      information for patients. FRES and FKGL are commonly used instruments to assess
      readability of written information. We also further analyzed major versus minor
      and patient-targeted versus professional Web sites. RESULTS: Overall DISCERN
      score was 2.20 +/- 0.60. Overall FRES score was 29.68 +/- 16.64. Overall FKGL
      score was 13.07 +/- 3.95. We found significant differences between patient
      targeted and professional Web sites on FRES (43.80 +/- 2.78 and 18.58 +/- 9.04,
      respectively) and FKGL (11.46 +/- 3.36 and 14.33 +/- 4.30, respectively) (P <
      0.00 and P = 0.01, respectively). We also found significant differences between
      major and minor Web sites on DISCERN (2.35 +/- 2.35 and 1.95 +/- 0.61,
      respectively), FRES (24.75 +/- 14.61 and 37.71 +/- 16.97, respectively), and FKGL
      (14.19 +/- 3.68 and 11.24 +/- 3.77, respectively) (P = 0.03, 0.01, and 0.01,
      respectively). CONCLUSIONS: Thyroplasty information available online is of
      suboptimal quality and written at a level too difficult for the average American
      adult to read comfortably. Major Web sites have higher quality information but
      are more difficult to read. Professional Web sites are also more difficult to
      read than patient-targeted Web sites.

PMID- 24314832
TI  - Controller design based on MU analysis and PSO algorithm.
AB  - In this paper an evolutionary algorithm is employed to address the controller
      design problem based on MU analysis. Conventional solutions to MU synthesis
      problem such as D-K iteration method often lead to high order, impractical
      controllers. In the proposed approach, a constrained optimization problem based
      on MU analysis is defined and then an evolutionary approach is employed to solve
      the optimization problem. The goal is to achieve a more practical controller with
      lower order. A benchmark system named two-tank system is considered to evaluate
      performance of the proposed approach. Simulation results show that the proposed
      controller performs more effective than high order H(infinity) controller and has
      close responses to the high order D-K iteration controller as the common solution
      to MU synthesis problem.

PMID- 24314831
TI  - Detection of chronic laryngitis due to laryngopharyngeal reflux using color and
      texture analysis of laryngoscopic images.
AB  - OBJECTIVE: To determine if pattern recognition of hue and textural parameters can
      be used to identify laryngopharyngeal reflux (LPR). METHODS: Laryngoscopic images
      from 20 subjects with LPR and 42 control subjects without LPR were obtained. LPR
      status was determined using the reflux finding score. Color and texture features
      were quantified using hue calculation and two-dimensional Gabor filtering. Five
      regions were analyzed: true vocal folds, false vocal folds, epiglottis,
      interarytenoid space, and arytenoid mucosae. A multilayer perceptron artificial
      neural network with varying numbers of hidden nodes was used to classify images
      according to pattern recognition. Receiver operating characteristic (ROC)
      analysis was used to evaluate diagnostic utility, and intraclass correlation
      coefficient analysis was performed to determine interrater reliability. RESULTS:
      Classification accuracy when including all parameters was 80.5% +/- 1.2% with an
      area under the ROC curve of 0.887. Classification accuracy decreased when
      including only hue (73.1% +/- 3.5%; area under the curve = 0.834) or texture
      (74.9% +/- 3.6%; area under the curve = 0.852) parameters. Interrater reliability
      was 0.97 +/- 0.03 for hue parameters and 0.85 +/- 0.11 for texture parameters.
      CONCLUSIONS: This preliminary study suggests that a combination of hue and
      texture features can be used to detect chronic laryngitis due to LPR. A simple,
      minimally invasive assessment would be a valuable addition to the currently
      invasive and somewhat unreliable methods currently used for diagnosis. Including
      more data will likely improve classification accuracy. Additional investigations
      will be performed to determine if results are in accordance with those provided
      by pH probe monitoring.

PMID- 24314833
TI  - Differential resistance feedback control of a self-sensing shape memory alloy
      actuated system.
AB  - There is a growing trend towards miniaturization, and with it comes an increasing
      need for miniature sensors and actuators for control. Moreover situations occur
      wherein implementation of external physical sensor is impossible, here self
      sensing lends its hand appropriately. Though self-sensing actuation (SSA) is
      extensively studied in piezoelectric, exploring this property in shape memory
      alloy is still under study. A simple scheme is developed which allows
      differential resistance measurement of antagonistic shape memory alloy actuated
      wires to concurrently sense and actuate in a closed loop system. The usefulness
      of the proposed scheme is experimentally verified by designing a one link
      manipulator arm and is performed in a real time tracking control. In a practical
      implementation of the self-sensing actuator a newly proposed signal processing
      electronic circuit is used for direct differential resistance feedback control
      upto a bandwidth of 1.8 Hz. The control design uses fuzzy PID which requires no
      detailed information about the constitutive model of SMA. At an operating
      frequency of 1 Hz, the result of the self-sensing feedback control with an
      angular tracking accuracy of +/-0.06 degrees  over a movement range of +/-15
      degrees  is demonstrated.

PMID- 24314834
TI  - Lack of a visible outcome marker fuels the perfect storm of Dr Singh's editorial.

PMID- 24314835
TI  - The ability of healthy volunteers to simulate a neurologic field defect on
      automated perimetry.
AB  - OBJECTIVE: To determine if volunteers can simulate and reproduce 3 types of
      neurologic field defects: hemianopia, quadrantanopia, and central scotoma.
      DESIGN: Cross-sectional study. PARTICIPANTS: Thirty healthy volunteers new to
      perimetry (including automated perimetry). METHODS: After informed consent,
      volunteers were randomized to 1 of the 3 visual field defects listed above. All
      visual field testing was performed on the right eye using the Humphrey Field
      Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA) SITA Fast 24-2 protocol. Each
      volunteer was provided with standard new patient instructions and was shown a
      diagram of the defect to be simulated. Two sets of visual fields were performed
      on the right eye with 10 minutes between tests. Three experts used the Ocular
      Hypertension Treatment Study reading center criteria and determined if the
      simulation was successful. MAIN OUTCOME MEASURES: Proportion of volunteers able
      to simulate the assigned visual field. RESULTS: All 10 volunteers (100%)
      successfully simulated a hemianopia on the first and second fields. All 10
      volunteers (100%) simulated a quadrantanopia on the first field and 9 (90%) did
      so on the second field. Eight volunteers (80%) successfully simulated a central
      scotoma in the first field and all 10 (100%) did so on in the second field.
      Reliability criteria were excellent. Forty-seven fields (78%) had 0 fixation
      losses, 48 (80%) had 0 false-positive results, and 44 (73%) had 0 false-negative
      results. CONCLUSIONS: It is easy to simulate reproducible and reliable neurologic
      field defects on automated perimetry using HFA.

PMID- 24314836
TI  - The spectrum of ocular alterations in patients with beta-thalassemia syndromes
      suggests a pathology similar to pseudoxanthoma elasticum.
AB  - PURPOSE: To determine the prevalence and spectrum of ocular fundus abnormalities
      in patients with beta-thalassemia and to investigate risk factors for their
      development. DESIGN: Cross-sectional, observational study. PARTICIPANTS: A total
      of 255 patients with beta-thalassemia major (TM) and beta-thalassemia intermedia
      (TI) were consecutively recruited and investigated. METHODS: Patients underwent
      best correct visual acuity, indirect ophthalmoscopy, and fundus photography,
      including fundus autofluorescence (FAF) and near-infrared reflectance imaging
      using a confocal scanning laser ophthalmoscope (cSLO). Hematologic parameters
      were determined, including mean ferritin levels, aspartate amino transferase,
      alanine amino transferase, calcium, pre-transfusion hemoglobin, history of
      splenectomy, and liver iron concentration. Factors associated with the ocular
      phenotype were assessed using logistic regression. MAIN OUTCOME MEASURES: Ocular
      phenotype as determined by clinical examination and used multimodal imaging.
      RESULTS: A total of 153 patients (60.0%) affected by TM and 102 patients (40.0%)
      affected by TI participated, of whom 216 (84.7%) were receiving iron-chelating
      therapy. Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum
      (PXE) were detected by cSLO in 70 of 255 patients (27.8%) and included peau
      d'orange (19.6%), angioid streaks (12.9%), pattern dystrophy-like changes (7.5%),
      and optic disc drusen (2.0%). Pseudoxanthoma elasticum-like changes were more
      frequent in patients with TI (P<0.001). Patients with PXE-like fundus changes
      were older than patients without these fundus changes (P<0.001). In both patients
      with TI and TM, age (P = 0.001) and splenectomy (P = 0.001) had the strongest
      association with presence of PXE-like fundus changes in multivariate analyses. A
      total of 43 of 255 patients (16.9%) showed increased retinal vascular tortuosity
      independently of the PXE-like fundus changes, which was associated with aspartate
      amino transferase (P = 0.036), hemoglobin (P = 0.008), and ferritin levels (P =
      0.005). CONCLUSIONS: Pseudoxanthoma elasticum-like fundus changes are a frequent
      finding in patients with beta-thalassemia. In TI, these changes increase with
      duration or severity of the disease. This particular ocular phenotype suggests an
      ocular pathology similar to PXE. Retinal vascular tortuosity may be an additional
      disease manifestation independent of the PXE-like syndrome. Patients with long
      standing disease requiring iron-chelating treatment and a history of splenectomy
      need regular ophthalmic checkups because they are at risk of developing PXE-like
      fundus changes and potentially of subsequent choroidal neovascularization.

PMID- 24314838
TI  - The effect of colored overlays on reading performance in infantile nystagmus.

PMID- 24314837
TI  - Vitrectomy with internal limiting membrane peeling versus no peeling for
      idiopathic full-thickness macular hole.
AB  - OBJECTIVE: To determine whether internal limiting membrane (ILM) peeling improves
      anatomic and functional outcomes of full-thickness macular hole (FTMH) surgery
      when compared with the no-peeling technique. DESIGN: Systematic review and
      individual participant data (IPD) meta-analysis undertaken under the auspices of
      the Cochrane Eyes and Vision Group. Only randomized controlled trials (RCTs) were
      included. PARTICIPANTS AND CONTROLS: Patients with idiopathic stage 2, 3, and 4
      FTMH undergoing vitrectomy with or without ILM peeling. INTERVENTION: Macular
      hole surgery, including vitrectomy and gas endotamponade with or without ILM
      peeling. MAIN OUTCOME MEASURES: Primary outcome was best-corrected distance
      visual acuity (BCdVA) at 6 months postoperatively. Secondary outcomes were BCdVA
      at 3 and 12 months; best-corrected near visual acuity (BCnVA) at 3, 6, and 12
      months; primary (after a single surgery) and final (after >1 surgery) macular
      hole closure; need for additional surgical interventions; intraoperative and
      postoperative complications; patient-reported outcomes (PROs) (EuroQol-5D and
      Vision Function Questionnaire-25 scores at 6 months); and cost-effectiveness.
      RESULTS: Four RCTs were identified and included in the review. All RCTs were
      included in the meta-analysis; IPD were obtained from 3 of the 4 RCTs. No
      evidence of a difference in BCdVA at 6 months was detected (mean difference, 
      0.04; 95% confidence interval [CI], -0.12 to 0.03; P=0.27); however, there was
      evidence of a difference in BCdVA at 3 months favoring ILM peeling (mean
      difference, -0.09; 95% CI, -0.17 to-0.02; P=0.02). There was evidence of an
      effect favoring ILM peeling with regard to primary (odds ratio [OR], 9.27; 95%
      CI, 4.98-17.24; P<0.00001) and final macular hole closure (OR, 3.99; 95% CI, 1.63
      9.75; P=0.02) and less requirement for additional surgery (OR, 0.11; 95% CI, 0.05
      0.23; P<0.00001), with no evidence of a difference between groups with regard to
      intraoperative or postoperative complications or PROs. The ILM peeling was found
      to be highly cost-effective. CONCLUSIONS: Available evidence supports ILM peeling
      as the treatment of choice for patients with idiopathic stage 2, 3, and 4 FTMH.

PMID- 24314839
TI  - Risk of scar in the comparison of age-related macular degeneration treatments
      trials.
AB  - OBJECTIVE: To describe risk factors for scar in eyes treated with ranibizumab or
      bevacizumab for neovascular age-related macular degeneration (AMD). DESIGN:
      Prospective cohort study within a randomized clinical trial. PARTICIPANTS:
      Patients with no scar on color fundus photography (CFP) or fluorescein
      angiography (FA) at enrollment in the Comparison of Age-related Macular
      Degeneration Treatments Trials (CATT). METHODS: Eyes were assigned to ranibizumab
      or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked
      readers assessed CFP and FA. Baseline demographic characteristics, visual acuity,
      morphologic features on photography and optical coherence tomography (OCT), and
      genotypes associated with AMD risk were evaluated as risk factors using adjusted
      hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were
      classified as fibrotic with well-demarcated elevated mounds of yellowish white
      tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying
      amounts of central depigmentation. MAIN OUTCOME MEASURES: Scar formation.
      RESULTS: Scar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline
      characteristics associated with greater risk of scarring were predominantly
      classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4-3.9) versus occult
      CNV, blocked fluorescence (aHR, 1.4; CI, 1.1-1.8), foveal retinal thickness >212
      MUm (aHR, 2.4; CI, 1.7-3.6) versus <120 MUm, foveal subretinal tissue complex
      thickness >275 MUm (aHR, 2.4; CI, 1.7-3.6) versus <=75 MUm, foveal subretinal
      fluid (aHR, 1.5; CI, 1.1-2.0) versus no subretinal fluid, and subretinal
      hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3-2.3) versus no SHRM. Eyes with
      elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5
      0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically
      significant association with scarring. Fibrotic scars developed in 24.7% of eyes,
      and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the
      scar types were similar except that eyes with larger lesion size or visual acuity
      <20/40 were more likely to develop fibrotic scars. CONCLUSIONS: Approximately
      half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic
      neovascularization, a thicker retina, and more fluid or material under the foveal
      center of the retina are more likely to develop scar.

PMID- 24314840
TI  - Associations between health-related quality of life and the decision to perform
      surgery for childhood intermittent exotropia.
AB  - OBJECTIVE: To assess associations between health-related quality of life (HRQOL)
      and the decision to perform strabismus surgery for children with intermittent
      exotropia. DESIGN: Retrospective chart review. PARTICIPANTS: Children with
      intermittent exotropia. METHODS: Included subjects, identified in a clinical
      practice, had assessment of HRQOL using the intermittent exotropia questionnaire
      (IXTQ), comprising child, proxy, and parent components (parent domains: function,
      psychosocial, and surgery). The IXTQ scores were evaluated for association with
      surgery, along with standard clinical measures: prism and alternate cover test
      (PACT), stereoacuity, and control score (mean of the 3 most recent scores).
      Included data were from preoperative examination (surgical cohort) or from most
      recent follow-up examination (nonsurgical cohort). Univariate and multivariate
      logistic regression analyses were performed, and relative risk (RR) ratios were
      calculated. Spearman rank correlations were calculated to identify highly
      correlated items. MAIN OUTCOME MEASURES: Association of individual factors with
      the decision to perform surgery, calculated using RR ratios. RESULTS: One hundred
      six children with intermittent exotropia (median age, 6 years; range, 2-16 years)
      were eligible for inclusion. Nineteen (18%) of 106 underwent surgery. Using all
      available data, the IXTQ proxy score, IXTQ parent function score, IXTQ parent
      psychosocial score, distance control score, near control score, near PACT, and
      Randot Preschool stereoacuity (Stereoptical Co, Inc, Chicago, IL) were associated
      with undergoing surgery (P<0.1). Sixty-nine of 106 patients had complete data on
      all factors identified in univariate analysis and were included in multivariate
      analyses. Fourteen (20%) of these 69 patients underwent surgery. In multivariate
      analyses, poor distance control score (RR, 1.83; 95% confidence interval [CI],
      1.25-2.68) and reduced IXTQ parent function score (RR, 0.96; 95% CI, 0.92-0.99)
      were associated with surgical intervention. Repeat multivariate analyses
      retaining only 1 of the highly correlated items showed IXTQ proxy, IXTQ parent
      psychosocial, larger near PACT, and worse near control were also associated with
      surgery. CONCLUSIONS: After accounting for poorer exodeviation control at
      distance, reduced parent and proxy HRQOL were associated with undergoing
      strabismus surgery for childhood intermittent exotropia. Recognizing reduced
      parental HRQOL may be important, with a possible role for educational or
      counselling interventions.

PMID- 24314841
TI  - Defining the limits of normal conjunctival fornix anatomy in a healthy South
      Asian population.
AB  - PURPOSE: Quantifying the extent of conjunctival fibrosis for documentation of
      progression in conjunctival scarring disease is a clinical challenge. Measurement
      of forniceal foreshortening facilitates monitoring of these disorders. This study
      aims (1) to define the limits of the normal human conjunctival fornices and how
      these alter with age and (2) to provide normative data for upper and lower fornix
      depths (FDs) and fornix intercanthal distance (FICD) within a healthy South
      Asian, racially distinct population. DESIGN: Epidemiologic, cross-sectional
      study. PARTICIPANTS: A total of 240 subjects with national origins from South
      Asia, with no known ocular history and normal adnexal and conjunctival
      examination, aged 20 to 80 years. METHODS: An FICD modification of a custom
      designed fornix depth measurer (FDM) was validated and used for measurement of
      both lower and upper FDs together with FICDs in 480 healthy eyes with no ocular
      comorbidities. Data were analyzed using repeated-measures analysis of variance
      and presented as means with 95% confidence intervals (CIs). MAIN OUTCOME
      MEASURES: Mean lower and upper FDs and FICD for the entire cohort, stratified
      according to age decade and sex. RESULTS: For this South Asian population, the
      overall upper and lower FDs were 15.3 mm (95% CI, 14.9-15.6) and 10.9 mm (95% CI,
      10.7-11.1), respectively, with FICD defined as 32.9 mm (95% CI, 32.5-33.4)
      (upper) and 31.7 mm (95% CI, 31.3-32.1) (lower). With increasing age, a
      progressive reduction of all measured parameters (P < 0.001) was noted, with
      female subjects having significantly shallower fornices (upper FD, P < 0.001;
      lower FD, P < 0.001; upper FICD, P = 0.081; and lower FICD, P = 0.015).
      CONCLUSIONS: This is the first study to define the limits of normal upper FD and
      FICDs in any population group. Our study demonstrates sex variations and
      progressive conjunctival shrinkage with age. Although it provides important,
      objective data for normal forniceal anatomy, further study is recommended in
      other populations to confirm the generalizability of these data or to enable
      normal comparative datasets for the assessment of conjunctival scarring disorders
      among all anthropological groups.

PMID- 24314842
TI  - Prospective masked comparison of intraoperative floppy iris syndrome severity
      with tamsulosin versus alfuzosin.
AB  - OBJECTIVE: To determine whether severe intraoperative floppy iris syndrome (IFIS)
      is more or equally likely with tamsulosin or alfuzosin. DESIGN: Prospective,
      masked, multicenter, cross-sectional study. PARTICIPANTS AND CONTROLS:
      Consecutive patients taking systemic tamsulosin or alfuzosin and scheduled for
      routine cataract surgery (case group) and patients with no history of systemic
      alpha1-antagonists scheduled for routine cataract surgery (control group).
      METHODS: Phacoemulsification with intraocular lens implantation was performed and
      recorded on video. Intracameral phenylephrine or epinephrine, either by direct
      injection or placement in the irrigation bottle, was not permitted. Every
      surgical video subsequently was reviewed remotely by 2 masked investigators who
      diagnosed the presence or absence of IFIS and graded the severity of IFIS as
      follows: none, mild (billowing only), moderate (billowing and either iris
      prolapse or >=2 mm of pupil constriction), or severe (billowing accompanied by
      iris prolapse and >=2 mm of pupil constriction). MAIN OUTCOME MEASURES: Rate and
      severity of IFIS and surgical complication rate. RESULTS: A total of 226 eyes (70
      in the tamsulosin group, 43 in the alfuzosin group, and 113 in the control group)
      were enrolled. Severe IFIS was noted in 34.3% (24/70) of the tamsulosin eyes and
      in 16.3% (7/43) of the alfuzosin eyes compared with 4.4% (5/113) of the control
      eyes. The differences between each of the 3 groups were statistically
      significant. In the absence of epinephrine in the irrigation bottle, 12.4% of
      control eyes had moderate to severe IFIS. There were no instances of posterior
      capsular rupture or significant surgical complications in either the case or
      control groups. CONCLUSIONS: Moderate to severe IFIS can occur in low-risk eyes
      when epinephrine is omitted from the irrigation bottle. Although both tamsulosin
      and alfuzosin significantly increase the risk of IFIS compared with patients
      without prior alpha1-antagonist intake, severe IFIS statistically was more likely
      with tamsulosin than with alfuzosin (P = 0.036). Patients with symptomatic benign
      prostatic hyperplasia and cataracts requiring a uroselective alpha1-antagonist
      may consider trying alfuzosin first.

PMID- 24314843
TI  - Testing for coevolutionary diversification: linking pattern with process.
AB  - Coevolutionary diversification is cited as a major mechanism driving the
      evolution of diversity, particularly in plants and insects. However, tests of
      coevolutionary diversification have focused on elucidating macroevolutionary
      patterns rather than the processes giving rise to such patterns. Hence, there is
      weak evidence that coevolution promotes diversification. This is in part due to a
      lack of understanding about the mechanisms by which coevolution can cause
      speciation and the difficulty of integrating results across micro- and
      macroevolutionary scales. In this review, we highlight potential mechanisms of
      coevolutionary diversification, outline approaches to examine this process across
      temporal scales, and propose a set of minimal requirements for demonstrating
      coevolutionary diversification. Our aim is to stimulate research that tests more
      rigorously for coevolutionary diversification. 

PMID- 24314845
TI  - [Idiopathic retroperitoneal fibrosis: a multicentric retrospective study of 30
      French cases and follow-up of the renal function].
AB  - PURPOSE: Idiopathic retroperitoneal fibrosis (IRF) is an inflammatory disorder,
      affecting the aorta and the surrounding vessels and tissues. The prognosis is
      mainly driven by the risks of chronic kidney disease and relapse. Our aim was to
      assess the prevalence of chronic kidney disease at follow-up. METHODS: We
      retrospectively reviewed the medical records of patients diagnosed for IRF in
      Seine-Saint-Denis (France) between 1987 and 2011. We collected informations about
      presentation, radiologic findings and follow-up. Diagnosis of IRF was confirmed
      when all the following criteria were met: infiltration of the infrarenal aorta or
      iliac vessels, absence of aneurysmal dilation, lack of clinical suspicion of
      malignancy. RESULTS: Thirty patients were identified, with a male/female ratio of
      4.9. Mean age was 55+/-13 years old. The mean creatinine clearance was 66
      mL/min/1.73 m(2) and the mean CRP was 45+/-36 mg/L. In 24 (80%) patients, the
      location of IRF was periaortic and periiliac. Eleven patients (37%) underwent a
      diagnostic biopsy, and 14 (47%) required an ureteral procedure. A mean follow-up
      of 63 months was available for 29 patients: 69% relapsed, 7 developed chronic
      renal disease (24%), and one died of urinary sepsis. Older age (P=0.023),
      diabetes (P=0.007), and initial renal insufficiency (P=0.05) were associated with
      a risk of chronic renal insufficiency. CONCLUSION: The high frequency of relapses
      and chronic renal disease emphasizes the need of close follow-up in patients
      diagnosed with IRF.

PMID- 24314846
TI  - [Statins: from data to routine prescription...].

PMID- 24314844
TI  - Insights into redox sensing metalloproteins in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis, the pathogen that causes tuberculosis, has evolved
      sophisticated mechanisms for evading assault by the human host. This review
      focuses on M. tuberculosis regulatory metalloproteins that are sensitive to
      exogenous stresses attributed to changes in the levels of gaseous molecules
      (i.e., molecular oxygen, carbon monoxide and nitric oxide) to elicit an
      intracellular response. In particular, we highlight recent developments on the
      subfamily of Whi proteins, redox sensing WhiB-like proteins that contain iron
      sulfur clusters, sigma factors and their cognate anti-sigma factors of which some
      are zinc-regulated, and the dormancy survival regulon DosS/DosT-DosR heme sensory
      system. Mounting experimental evidence suggests that these systems contribute to
      a highly complex and interrelated regulatory network that controls M.
      tuberculosis biology. This review concludes with a discussion of strategies that
      M. tuberculosis has developed to maintain redox homeostasis, including mechanisms
      to regulate endogenous nitric oxide and carbon monoxide levels. 

PMID- 24314847
TI  - Intracranial hypotension in the setting of concurrent perineural cyst rupture and
      subarachnoid hemorrhage.
AB  - Although most patients with intracranial hypotension typically present with
      headaches, the rest of the clinical spectrum is characteristically non-specific
      and often quite variable. In a patient with concurrent pathologies that can
      produce a similar clinical picture, a high index of suspicion must be maintained
      to achieve the correct diagnosis. The authors report a patient with intracranial
      hypotension in the setting of concurrent perineural cyst rupture and subarachnoid
      hemorrhage. A 63-year-old woman with a family history of ruptured intracranial
      aneurysms presented after a sudden thunderclap headache and was found to have
      diffuse subarachnoid hemorrhage. Imaging revealed anterior communicating and
      superior hypophyseal artery aneurysms. Following the uneventful clipping of both
      aneurysms, the patient experienced a delayed return to her neurological baseline.
      After it was noted that the patient had an improved neurological examination when
      she was placed supine, further investigation confirmed intracranial hypotension
      from perineural cyst rupture. The patient improved and returned to her
      neurological baseline after undergoing a high-volume blood patch and remained
      neurologically intact at postoperative follow-up. Although intracranial
      hypotension is known to be commonly associated with cerebrospinal fluid leak, its
      causal and temporal relationship with subarachnoid hemorrhage has yet to be
      elucidated. 

PMID- 24314848
TI  - Spinal motion and intradiscal pressure measurements before and after lumbar spine
      instrumentation with titanium or PEEK rods.
AB  - Spinal instrumentation and fusion have been incriminated as contributing to
      adjacent segment degeneration (ASD). It has been suggested that ASD results from
      increased range of motion and intradiscal pressure (IDP) adjacent to
      instrumentation. Posterior dynamic stabilization with polyetheretherketone (PEEK)
      rods has been proposed as potentially advantageous compared to rigid
      instrumentation with titanium (Ti) rods in reducing the incidence of ASD. We
      evaluated segmental motions in the cadaveric spine instrumented with PEEK or Ti
      rods from L3 to S1, as well as the adjacent segment motions and IDP at L1-2 and
      L2-3. Human cadaveric spines were potted at T12-L1 and S1-2. Spinal
      instrumentation from L3-S1 was accomplished using pedicle screws with either PEEK
      or Ti rods. Specimens were subjected to displacement controlled testing: 15
      degrees  flexion, 15 degrees  extension, 10 degrees  lateral bending, and 5
      degrees  right axial rotation using the MTS machine (MTS, Minneapolis, MN, USA).
      Intradiscal pressure was measured by placing pressure transducers into the
      intervertebral disc at L1-2 and L2-3. Spinal motion of L2 relative to L3, and L3
      relative to S1 was tracked using a three dimensional motion analysis system.
      Instrumentation with PEEK and Ti rods was associated with a decrease in L3-S1
      motion compared to the intact state that was significant in flexion (p=0.002),
      and extension (p=0.0075). Instrumentation with PEEK and Ti rods was associated
      with an increase in IDP at L1-2 that was significant in flexion (p=0.0028).
      Instrumentation with either PEEK or Ti rods resulted in decreased motion at the
      instrumented levels while increasing IDP at the adjacent level. 

PMID- 24314849
TI  - Effects of the aspartic protease inhibitor from Lupinus bogotensis seeds on the
      growth and development of Hypothenemus hampei: an inhibitor showing high homology
      with storage proteins.
AB  - The coffee berry borer Hypothenemus hampei is a pest that causes great economic
      damage to coffee grains worldwide. Because the proteins consumed are digested by
      aspartic proteases in the insect's midgut, the inhibition of these proteases by
      transferring a gene encoding an aspartic protease inhibitor from Lupinus
      bogotensis Benth. to coffee plants could provide a promising strategy to control
      this pest. Five aspartic protease inhibitors from L. bogotensis (LbAPI) were
      accordingly purified and characterized. The gene encoding the L. bogotensis
      aspartic protease inhibitor (LbAPI), with the highest inhibitory activity against
      H. hampei, was expressed in Escherichia coli and the purified recombinant protein
      (rLbAPI), with a molecular mass of 15 kDa, was subsequently assessed for its
      ability to inhibit the aspartic protease activity present in the H. hampei midgut
      in vitro, as well as its effects on the growth and development of H. hampei in
      vivo. The in vitro experiments showed that rLbAPI was highly effective against
      aspartic proteases from H. hampei guts, with a half maximal inhibitory
      concentration (IC50) of 2.9 MUg. The in vivo experiments showed that the
      concentration of rLbAPI (w/w) in the artificial diet necessary to cause 50%
      mortality (LD50) of the larvae was 0.91%. The amino acid sequence of LbAPI had
      high homology (52-80%) to the seed storage proteins, vicilin and beta-conglutin,
      suggesting that this protein was generated by evolutionary events from a beta
      conglutin precursor. Based on these results, LbAPI may have a dual function as
      storage protein, and as defense protein against H. hampei. These results provide
      a promising alternative to obtain a coffee plant resistant to H. hampei.

PMID- 24314850
TI  - Substance use disorders in association with attention-deficit/hyperactivity
      disorder, co-morbid mental disorders, and medication in a nationwide sample.
AB  - BACKGROUND: The association of substance use disorders (SUD) with attention
      deficit disorder (ADHD), co-morbid mental disorders, and medication has only been
      studied in isolation and in rather small samples. PROCEDURE: Data were based on
      four Danish national registers covering a total of 20,742 patients with ADHD,
      their dispensed medications, co-morbid mental disorders, and associated SUD
      between 1994 and 2010. The analyses considered the risk of various medications
      (methylphenidate only, antidepressants only, antipsychotic only, mixed
      medication) in comparison to a control group of non-medicated patients with ADHD,
      various co-morbid disorders, duration of medication, age at diagnosis, year of
      birth, and sex for developing SUD. RESULTS: The observation period of the cohort
      ranged between 2.25 and 66.21 years and the prevalence for SUD was 9.51%. The SUD
      rates were significantly higher prior to, compared to following the onset of
      medication in the methylphenidate and the mixed medication subgroup, whereas they
      were significantly higher following onset of medication in the antidepressants
      and the antipsychotics subgroups. However, the SUD rates were significantly
      higher in all drug conditions except for methylphenidate after onset of
      medication compared to the non-medicated subgroup. Risk factors obtained by
      regression analysis did not include methylphenidate but did include
      antidepressants, antipsychotics, and mixed medications, in combination with co
      morbid mood, anxiety, personality, and conduct disorders, and older age at
      diagnosis. Longer duration of medication and female sex were protective factors.
      CONCLUSIONS: This representative study based on a large nationwide psychiatric
      sample provides solid evidence into the patterns of SUD in patients with ADHD
      based on medication use and co-morbidities.

PMID- 24314851
TI  - Negative symptoms, past and present: a historical perspective and moving to DSM
      5.
AB  - The diagnosis of schizophrenia includes "positive" and "negative" symptoms. These
      titles were developed to respectively reflect if the symptoms are additions to
      normal experiences, such as delusions and hallucinations, or if they refer to the
      absence or the loss of normal emotional function or behavior. This paper
      describes the history of the negative symptom concept, from its origins up to the
      considerations for the DSM-5, including the steps that produced the current
      conceptualizations. The DSM-5 only includes deficits in emotional expression and
      avolition as negative symptoms, which can be assessed from interview information.
      Factor analyses show they encompass most other negative symptom items. In
      addition to using these negative symptoms in a categorical manner to make a
      diagnosis, the DSM-5 has quantitative severity ratings of the negative symptoms,
      along with ratings of delusions, cognitive symptoms, motor symptoms,
      disorganization, depression and mania. With this approach, the different symptom
      domains, including negative symptoms, can be measured and tracked over time.
      Another change in the DSM-5 is the dropping of the schizophrenia subtypes that
      have been included in earlier volumes, as they were not useful in treatment
      decisions or prognosis. An intended outcome of these changes in DSM-5 is for
      clinicians to directly treat the individual psychopathological domains of the
      disorder for optimizing individual outcomes. Finally, this paper includes
      descriptions of the negative symptom items from over a dozen different scales. 

PMID- 24314852
TI  - Routine clinical assessment of cognitive functioning in schizophrenia, major
      depressive disorder, and bipolar disorder.
AB  - As more evidence points to the association of cognitive dysfunction with mental
      health disorders, the assessment of cognitive function in routine clinical care
      of these disorders is increasingly important. Despite this, it remains unknown
      how cognitive function is measured in routine clinical practice. The objective of
      this study was to assess psychiatrists' awareness of cognitive dysfunction in
      mental health disorders and their methods of cognitive assessment. An online
      survey was disseminated to psychiatrists in Europe, Asia, Australia and the
      United States. The survey asked about their perceptions of cognitive dysfunction
      in several mental health disorders, knowledge of cognitive assessment, method of
      cognitive assessment, and instruments used to measure cognitive function. Among
      the 61 respondents, most perceived that schizophrenia was associated with the
      greatest cognitive dysfunction. Many were unaware whether guidelines were
      available on cognitive assessment. In schizophrenia, 59% of psychiatrists
      reportedly used cognitive instruments, while the remainder relied solely on
      patient history interviews. The use of instruments to assess cognition in major
      depressive disorder (MDD) and bipolar disorder (BPD) was lower, 38% and 37%
      respectively. Of the reported instruments used, only a few were actually
      appropriate for use in the diseases of interest (12% in schizophrenia, 3% in MDD
      and 0% in BPD). Other instruments reported were clinical measures that did not
      assess cognition. These findings reveal some inconsistencies in psychiatrists'
      routine clinical evaluation of cognitive function. There appeared to be low use
      of true cognitive assessment instruments in clinical practice and confusion
      regarding what constituted a cognitive assessment instrument. 

PMID- 24314853
TI  - Short-term effects of erythropoietin on neurodevelopment in infants with cerebral
      palsy: a pilot study.
AB  - OBJECTIVE: Cerebral palsy (CP) is a disabling condition characterized by the
      motor impairment, which is difficult to be ameliorated. In the brain of infants
      with CP, there are persistent pathomechanisms including accentuated
      neuroinflammation. Since erythropoietin was demonstrated to have neuroprotective
      effect via anti-inflammatory and anti-apoptotic properties, we hypothesized that
      the administration of recombinant human EPO (rhEPO) could help children with CP,
      especially young infants. MATERIALS AND METHOD: We investigated the therapeutic
      efficacy of rhEPO for infants with CP, who had been undergoing active
      rehabilitation in hospitalized setting to eliminate treatment bias. Twenty
      infants with CP were randomly divided into EPO or control group equally. We
      compared the changes in the Gross Motor Function Measure (GMFM) and the Bayley
      Scales of Infant Development-II (BSID-II) scores during one month of
      hospitalization between two groups. RESULTS: The improvements after 1 month on
      the GMFM A and GMFM total scores differed significantly between the groups (p =
      0.003, p = 0.04, respectively). However, the changes after 6 months were not
      different between the two groups. The scores of BSID-II did not show any
      differences at 1-month and 6-months post-treatment. CONCLUSION: These results
      indicated that rhEPO could have therapeutic efficacy for infants with CP during
      the active rehabilitation and anti-inflammation was suggested to be one of its
      therapeutic mechanisms.

PMID- 24314854
TI  - Continuing care for patients with alcohol use disorders: a systematic review.
AB  - BACKGROUND: A chronic care perspective should be adopted in the treatment of
      patients with alcohol use disorders (AUDs). Initial treatment in a more intense
      psychiatric care setting should be followed by continuing care. This systematic
      review aims to identify effective continuing care interventions for patients with
      AUDs. METHODS: Electronic databases were searched up to February 2013 (MEDLINE,
      EMBASE, CENTRAL, CINAHL and PsycINFO) to identify RCTs studying continuing care
      interventions for patients with AUDs. Study selection and quality appraisal was
      done independently by two reviewers. Drinking and treatment engagement outcomes
      were considered. Relative risks and mean differences were calculated with 95%
      confidence intervals. A statistical pooling of results was planned. RESULTS: 20
      trials out of 15,235 identified studies met the inclusion criteria. Only six were
      evaluated as methodologically strong enough and included for further analysis.
      Interventions ranged from telephone calls and nurse follow-up to various forms of
      individual or couples counseling. Four trials suggested that supplementing usual
      continuing care with an active intervention empowering the patient, could be
      beneficial to drinking outcomes. Effect sizes were limited and not consistent
      across all outcomes. Because of heterogeneity in the interventions and outcome
      measures, a meta-analysis could not be performed. CONCLUSION: For the treatment
      of a disease with such devastating consequences, it is remarkable how few high
      quality studies are available. Adding an active intervention to usual continuing
      care seems to improve treatment outcomes. We propose an integrated care program
      with different elements from the selected studies and discuss implications for
      further research.

PMID- 24314855
TI  - Reply to the Comments on the "No-Prop" algorithm.

PMID- 24314856
TI  - [Potential indications for helical tomotherapy in breast cancers].
AB  - PURPOSE: To evaluate the dosimetric gain obtained in either the planning target
      volume or organs at risk coverage by the use of intensity-modulated radiation
      therapy in some particular postoperative breast cancers. PATIENTS AND METHOD:
      Prospective dosimetric comparison between monoisocentric conformal radiotherapy
      and intensity-modulated radiation therapy in nine patient files. RESULTS: Using
      intensity-modulated radiation therapy was shown to improve in each case, at least
      one conformity, homogeneity, and coverage index either for planning target
      volumes or for organs at risk. Intensity-modulated radiation therapy was
      therefore always chosen rather than conformal monoisocentric radiotherapy.
      CONCLUSIONS: Indications to retain intensity-modulated radiation therapy would
      consist of bilateral lesions, pectus excavatum, past thoracic irradiation
      (Hodgkin's disease) and complex volumes in obese or overweight patients.

PMID- 24314858
TI  - Reducing ventilator associated pneumonia in adult patients through high standards
      of oral care: a historical control study.
AB  - OBJECTIVES: Implement and evaluate the impact of oral hygiene measures (teeth
      brushing, 1% oral chlorhexidine and oropharyngeal suction) on the incidence of
      ventilator-associated pneumonia (VAP) and the costs of prevention and treatment.
      DESIGN: A historical control study of all 1087 patients, mechanically ventilated
      for at least 48hours in a general adult critical care unit, between July 2009 and
      December 2011. The incidence of VAP in 528 patients before a practice change was
      compared with the incidence in 559 patients after a practice change. The clinical
      audit cycle was used to review compliance with existing standards and implement a
      regime of enhanced oral hygiene. The costs of changing the oral care regime and
      the treatment of VAP with antibiotics was calculated. SETTING: 22 bed combined
      intensive care and high dependency unit in England. MAIN OUTCOME MEASURES: (1)
      Compliance with standards for oral care. (2) The incidence of VAP before and
      after the change. RESULTS: 91% (95% CI 90-93%) compliance with the standards for
      oral care was achieved throughout the 30 months of the study with very little
      difference before (90%, 95% CI 88-93%) and after (92%, 95% CI 90-95%) the changes
      in oral care standards were introduced. Of 528 patients mechanically ventilated
      for at least 48 hours before the change, 47 developed VAP. The mean incidence of
      VAP was 0.09 (8.9%) (95% CI 0.07-0.12). The mean VAP per 1000 ventilator days was
      13.6 (95% CI 13.1-14.0). After the change 24 of 559 patients developed VAP. The
      mean incidence of VAP after the change was 0.04 (4.1%) (95% CI 0.03-0.06). The
      mean VAP per 1000 ventilator days was 6.9 (95% CI 6.5-7.1). There was a L6319
      ($10,112, ?7518) cost saving on preventing and treating VAP following the
      practice change. A statistically significant difference (p<0.01) was seen between
      the incidence of VAP expected and that observed after the change in oral care.
      This represents a relative risk reduction of 0.53 (95% CI 0.25-0.71) and number
      needed to treat (NNT) of 21. CONCLUSION: An enhanced oral care bundle,
      incorporating 1% Chlorhexidine Gluconate, was associated with a significant
      reduction in VAP and the costs of treating VAP. Limitations of the study relate
      to analysis of other variables, in particular severity of illness, between the
      two groups and the lack of agreement in the literature on VAP criteria, which
      limits generalisation of these findings.

PMID- 24314857
TI  - Comparative study of the effect of warm saline mouth rinse on complications after
      dental extractions.
AB  - The aim of the present study was to determine the effect of saline mouth rinse on
      postoperative complications following routine dental extractions. Patients aged
      >=16 years, who were referred to the oral surgery clinic with an indication for
      non-surgical extraction of pathologic teeth, were prospectively and uniformly
      randomized into three groups. Group A (n=40) were instructed to gargle six times
      daily with warm saline and group B (n=40) twice daily; group C (n=40) were not
      instructed to gargle with warm saline and served as controls. Information on
      demographic characteristics, indications for extraction, and the development of
      complications, such as alveolar osteitis, acute inflamed socket, and acute
      infected socket, was obtained and analyzed. There were no significant differences
      between patients who gargled six times daily with warm saline and those who
      gargled twice daily with reference to either alveolar osteitis or acute inflamed
      socket (P>0.05). However saline mouth rinses at either frequency were beneficial
      in the prevention of alveolar osteitis in comparison with those who did not
      rinse. A twice-daily saline mouth rinse regimen is more convenient, and patient
      compliance may be better than with a six times daily rinse regimen.

PMID- 24314859
TI  - Detection of pigment network in dermoscopy images using supervised machine
      learning and structural analysis.
AB  - By means of this study, a detection algorithm for the "pigment network" in
      dermoscopic images is presented, one of the most relevant indicators in the
      diagnosis of melanoma. The design of the algorithm consists of two blocks. In the
      first one, a machine learning process is carried out, allowing the generation of
      a set of rules which, when applied over the image, permit the construction of a
      mask with the pixels candidates to be part of the pigment network. In the second
      block, an analysis of the structures over this mask is carried out, searching for
      those corresponding to the pigment network and making the diagnosis, whether it
      has pigment network or not, and also generating the mask corresponding to this
      pattern, if any. The method was tested against a database of 220 images,
      obtaining 86% sensitivity and 81.67% specificity, which proves the reliability of
      the algorithm. 

PMID- 24314861
TI  - Dietary fish oil reduces systemic inflammation and ameliorates sepsis-induced
      liver injury by up-regulating the peroxisome proliferator-activated receptor
      gamma-mediated pathway in septic mice.
AB  - This study investigated the effect of dietary fish oil on systemic inflammation
      and hepatic injury in mice with polymicrobial sepsis. Male ICR mice were assigned
      to a control group (C, n=30) and a fish oil group (FO, n=30). Mice in the C group
      were fed a semi-purified diet with 10% soybean oil, and those in the FO group
      were fed a fish oil diet (2.5% fish oil+7.5% soybean oil; w/w). Three weeks
      later, sepsis was induced by cecal ligation and puncture (CLP), and mice were
      sacrificed at 0, 6 and 24 h after CLP, respectively. Results showed that compared
      with C group, the FO group had lower plasma levels of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, IL-10, and nitrite at 6 and 24 h after CLP. Also,
      peritoneal lavage fluid concentrations of TNF-alpha and prostaglandin (PG) E2
      were significantly lower at 24 h in the FO than in the C group. The FO group had
      lower myeloperoxidase activities at 6 h after CLP in various organs. Plasma
      aminotransferase and alanine aminotransferase activities revealed significantly
      decreased in the FO group. The DNA-binding activity of peroxisome proliferators
      activated receptor gamma (PPARgamma) and mRNA expression of I kappaB alpha
      (IkappaBalpha) were up-regulated while nuclear factor (NF)-kappaB p65 DNA-binding
      activity, inducible nitric oxide synthase protein expression and the
      concentration of nitrotyrosine were significantly decreased in the FO group in
      liver after CLP. These results indicate that dietary fish oil administration may
      attenuate systemic inflammation and up-regulate hepatic PPARgamma DNA-binding
      activity, which may consequently have ameliorated liver injury in these septic
      mice. 

PMID- 24314862
TI  - Curcumin prevents leptin-induced tight junction dysfunction in intestinal Caco-2
      BBe cells.
AB  - Maintaining tight junction (TJ) integrity in the intestine is critical for
      nutrient absorption, host defense, and host immunity. While leptin secreted from
      adipose tissue is associated with obesity and obesity-related intestinal
      inflammation, the role of luminal leptin in intestinal TJ function is elusive.
      Here, we examined the role of leptin in intestinal TJ function in Caco-2 BBe
      cells and further explored the function of curcumin (CCM) in leptin-induced TJ
      dysfunction. Apical leptin, but not basolateral leptin, treatment at a
      concentration of 100 ng/ml deteriorated TJ function in Caco-2 BBe cells. Leptin
      impaired TJ alteration was resulted from induction of leptin receptor-dependent
      JAK2/STAT3 signaling pathway and its-related PI3K/Akt/ERK1/2 signaling pathways.
      Apical leptin also lowered the expression levels of genes encoding TJ-associated
      proteins such as zonula occludens-3, claudin-5, and occludin, and elevated
      expression of pro-inflammatory genes such as IL-6 and TNF-alpha. Leptin-impaired
      TJ junction in Caco-2 BBe cells was blunted by a 30-min CCM pretreatment through
      inhibition of leptin receptor-dependent signaling pathway, and its-associated
      induction of expression of genes encoding TJ-associated proteins and pro
      inflammatory cytokines. Our results elucidate a novel function of luminal leptin
      in intestinal TJ dysfunction, and further identify CCM as an effective dietary
      compound that prevents leptin-impaired TJ function in intestinal cells. 

PMID- 24314863
TI  - Mechanism of action of pre-meal consumption of whey protein on glycemic control
      in young adults.
AB  - Whey protein (WP), when consumed in small amounts prior to a meal, improves post
      meal glycemic control more than can be explained by insulin-dependent mechanisms
      alone. The objective of the study was to identify the mechanism of action of WP
      beyond insulin on the reduction of post-meal glycemia. In a randomized crossover
      study, healthy young men received preloads (300 ml) of WP (10 and 20 g), glucose
      (10 and 20 g) or water (control). Paracetamol (1.5 g) was added to the preloads
      to measure gastric emptying. Plasma concentrations of paracetamol, glucose, and
      beta-cell and gastrointestinal hormones were measured before preloads (baseline)
      and at intervals before (0-30 min) and after (50-230 min) a preset pizza meal (12
      kcal/kg). Whey protein slowed pre-meal gastric emptying rate compared to the
      control and 10 g glucose (P<.0001), and induced lower pre-meal insulin and C
      peptide than the glucose preloads (P<.0001). Glucose, but not WP, increased pre
      meal plasma glucose concentrations (P<.0001). Both WP and glucose reduced post
      meal glycemia (P=.0006) and resulted in similar CCK, amylin, ghrelin and GIP
      responses (P<.05). However, compared with glucose, WP resulted in higher post
      meal GLP-1 and peptide tyrosine-tyrosine (PYY) and lower insulin concentrations,
      without altering insulin secretion and extraction rates. For the total duration
      of this study (0-230 min), WP resulted in lower mean plasma glucose, insulin and
      C-peptide, but higher GLP-1 and PYY concentrations than the glucose preloads. In
      conclusion, pre-meal consumption of WP lowers post-meal glycemia by both insulin
      dependent and insulin-independent mechanisms. 

PMID- 24314864
TI  - Copper promotion of angiogenesis in isolated rat aortic ring: role of vascular
      endothelial growth factor.
AB  - Copper stimulation of angiogenesis at the organ system level is vascular
      endothelial growth factor (VEGF) dependent, but copper stimulation of vascular
      endothelial cell proliferation in cultures is VEGF independent. The present study
      was undertaken to use isolated rat aortic rings to understand the seemly
      controversial observations between in vivo and in vitro studies. The thoracic
      aorta was isolated from Sprague Dawley rats (8-10 weeks) and sectioned into 1.0
      mm thick vascular rings for culturing. Copper sulfide at a final concentration of
      5, 25, 50 or 100 MUM was added to the cultures and maintained for 8 days. A
      copper chelator, tetraethylenepentamine (TEPA) at a final concentration of 25
      MUM, was added to some cultures to block the effect of copper. An anti-VEGF
      antibody was used to determine the role of VEGF in copper promotion of
      angiogenesis. The data obtained showed that copper at 5 MUM in cultures
      stimulated the vascular formation; an effect was blocked by TEPA. Copper at
      concentrations above 50 MUM lost the proangiogenesis effect. However, copper at 5
      MUM did not enhance the production of VEGF, and concentrations above 50 MUM
      significantly increased VEGF production. On the other hand, the treatment with
      anti-VEGF antibody completely blocked the proangiogenesis effect of 5-MUM copper.
      This study thus demonstrates that VEGF is essential for angiogenesis but the
      proangiogenesis effect of copper does not act through enhanced production of
      VEGF. 

PMID- 24314860
TI  - Novel insights of dietary polyphenols and obesity.
AB  - The prevalence of obesity has steadily increased over the past three decades both
      in the United States and worldwide. Recent studies have shown the role of dietary
      polyphenols in the prevention of obesity and obesity-related chronic diseases.
      Here, we evaluated the impact of commonly consumed polyphenols, including green
      tea catechins, especially epigallocatechin gallates, resveratrol and curcumin, on
      obesity and obesity-related inflammation. Cellular studies demonstrated that
      these dietary polyphenols reduce viability of adipocytes and proliferation of
      preadipocytes, suppress adipocyte differentiation and triglyceride accumulation,
      stimulate lipolysis and fatty acid beta-oxidation, and reduce inflammation.
      Concomitantly, the polyphenols modulate signaling pathways including the
      adenosine-monophosphate-activated protein kinase, peroxisome proliferator
      activated receptor gamma, CCAAT/enhancer binding protein alpha, peroxisome
      proliferator activator receptor gamma activator 1-alpha, sirtuin 1, sterol
      regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear
      factor-kappaB that regulate adipogenesis, antioxidant and anti-inflammatory
      responses. Animal studies strongly suggest that commonly consumed polyphenols
      described in this review have a pronounced effect on obesity as shown by lower
      body weight, fat mass and triglycerides through enhancing energy expenditure and
      fat utilization, and modulating glucose hemostasis. Limited human studies have
      been conducted in this area and are inconsistent about the antiobesity impact of
      dietary polyphenols probably due to the various study designs and lengths,
      variation among subjects (age, gender, ethnicity), chemical forms of the dietary
      polyphenols used and confounding factors such as other weight-reducing agents.
      Future randomized controlled trials are warranted to reconcile the discrepancies
      between preclinical efficacies and inconclusive clinic outcomes of these
      polyphenols. 

PMID- 24314865
TI  - Heart energy metabolism impairment in Western-diet induced obese mice.
AB  - Nutritional transition has contributed to growing obesity, mainly by changing
      eating habits of the population. The mechanisms by which diet-induced obesity
      leads to cardiac injury are not completely understood, but it is known that
      obesity is associated to impaired cardiac function and energy metabolism,
      increasing morbidity and mortality. Therefore, our study aimed to investigate the
      mechanisms underlying cardiac metabolism impairment related to Western diet
      induced obesity. After weaning, male Swiss mice were fed a Western diet for 16
      weeks in order to induce obesity. After this period, the content of proteins
      involved in heart energy metabolism GLUT1, cytosolic lysate and plasma membrane
      GLUT4, AMPK, pAMPK, IRbeta, IRS-1, PGC-1alpha, CPT1 and UCP2 was evaluated. Also,
      the oxidative phosphorylation of myocardial fibers was measured by high
      resolution respirometry. Mice in the Western diet group (WG) presented altered
      biometric parameters compared to those in control group, including higher body
      weight, increased myocardial lipid deposition and glucose intolerance, which
      demonstrate the obesogenic role of Western diet. WG presented increased CPT1 and
      UCP2 contents and decreased IRS-1, plasma membrane GLUT4 and PGC-1alpha contents.
      In addition, WG presented cardiac mitochondrial dysfunction and reduced
      biogenesis, demonstrating a lower capacity of carbohydrates and fatty acid
      oxidation and also decreased coupling between oxidative phosphorylation and
      adenosine triphosphate synthesis. Cardiac metabolism impairment related to
      Western diet-induced obesity is probably due to damaged myocardial oxidative
      capacity, reduced mitochondrial biogenesis and mitochondria uncoupling, which
      compromise the bioenergetic metabolism of heart. 

PMID- 24314867
TI  - Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin
      pathway in a rodent model of obesity and type 2 diabetes.
AB  - Nicotinic acid (NA) and nicotinamide (NAM) are major forms of niacin and exert
      their physiological functions as precursors of nicotinamide adenine dinucleotide
      (NAD). Sirtuins, which are NAD-dependent deacetylases, regulate glucose and lipid
      metabolism and are implicated in the pathophysiology of aging, diabetes, and
      hepatic steatosis. The aim of this study was to investigate the effects of two
      NAD donors, NA and NAM, on glucose metabolism and the hepatic NAD-sirtuin
      pathway. The effects were investigated in OLETF rats, a rodent model of obesity
      and type 2 diabetes. OLETF rats were divided into five groups: (1) high fat (HF)
      diet, (2) HF diet and 10 mg NA/kg body weight (BW)/day (NA 10), (3) HF diet and
      100 mg NA/kg BW/day (NA 100), (4) HF diet and 10 mg NAM/kg BW/day (NAM 10), and
      (5) HF diet and 100 mg NAM/kg BW/day (NAM 100). NA and NAM were delivered via
      drinking water for four weeks. NAM 100 treatment affected glucose control
      significantly, as shown by lower levels of accumulative area under the curve
      during oral glucose tolerance test, serum fasting glucose, serum fasting insulin,
      and homeostasis model assessment of insulin resistance, and higher levels of
      serum adiponectin. With regard to NAD-sirtuin pathway, intracellular nicotinamide
      phosphoribosyltransferase, NAD, the NAD/NADH ratio, Sirt1, 2, 3, and 6 mRNA
      expressions, and Sirt1 activity all increased in livers of NAM 100-treated rats.
      These alterations were accompanied by the increased levels of proliferator
      activated receptor gamma, coactivator 1 alpha and mitochondrial DNA. The effect
      of NA treatment was less evident than that of NAM 100. These results demonstrate
      that NAM is more effective than NA on the regulation of glucose metabolism and
      the NAD-sirtuin pathway, which may relate to the altered mitochondrial
      biogenesis. 

PMID- 24314866
TI  - Murine CD8+ T cells but not macrophages express the vitamin D 1alpha-hydroxylase.
AB  - The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is
      synthesized by the 1alpha-hydroxylase, which is encoded by the Cyp27B1 gene.
      Using transgenic mice that have replaced the Cyp27B1 gene with the bacterial lacZ
      reporter gene (beta-galactosidase), the inflammatory conditions that induce
      Cyp27B1 in the immune system were probed. A variety of stimuli including
      lipopolysaccharide, anti-CD3 or PMA/ionomycin were used to stimulate splenocytes
      and bone marrow derived macrophage in vitro. Only anti-CD3 stimulation resulted
      in a low induction of beta-galactosidase activity in the spleen, indicating that
      T cells might be a source of Cyp27B1. In vivo, challenge with lipopolysaccharide,
      alpha-galactosylceramide, and Listeria monocytogenes failed to induce beta
      galactosidase activity outside of the kidneys. During more prolonged and severe
      inflammation there was staining in both the lungs and the gastrointestinal tract
      for beta-galactosidase. Furthermore, wild-type reconstitution of the
      hematopoietic cell population in Cyp27B1 KO mice protected the mice from
      experimental colitis. T cell production of Cyp27B1 activity was shown to be from
      the CD8+ but not the CD4+ T cell population. CD8+ T cells expressed the reporter
      gene only after 48 h of stimulation. The data is consistent with a model where
      CD8+ T cells are activated to produce Cyp27B1 and 1,25(OH)2D3 that serves to turn
      off the local immune response. 

PMID- 24314869
TI  - Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin
      signaling and toll-like receptor expression in rats fed a high-fat diet.
AB  - Insulin resistance (IR) has been identified as crucial pathophysiological factor
      in the development and progression of non-alcoholic fatty liver disease (NAFLD).
      Although mounting evidence suggests that perturbation of gut microflora
      exacerbates the severity of chronic liver diseases, therapeutic approaches using
      synbiotic has remained overlooked. Here, we show that a synbiotic composed by
      Lactobacillus paracasei B21060 plus arabinogalactan and fructo-oligosaccharides
      lessens NAFLD progression in a rat model of high fat feeding. IR and steatosis
      were induced by administration of high fat diet (HFD) for 6 weeks. Steatosis and
      hepatic inflammation, Toll-like receptor (TLR) pattern, glucose tolerance,
      insulin signaling and gut permeability were studied. Liver inflammatory markers
      were down-regulated in rats receiving the synbiotic, along with an increased
      expression of nuclear peroxisome proliferator-activated receptors and expression
      of downstream target genes. The synbiotic improved many aspects of IR, such as
      fasting response, hormonal homeostasis and glycemic control. Indeed it prevented
      the impairment of hepatic insulin signaling, reducing the phosphorylation of
      insulin receptor substrate-1 in Ser 307 and down-regulating suppressor of
      cytokine signaling 3. Gene expression analysis revealed that in the liver the
      synbiotic reduced cytokines synthesis and restored the HFD-dysregulated TLR 2, 4
      and 9 mRNAs toward a physiological level of expression. The synbiotic preserved
      gut barrier integrity and reduced the relative amount of Gram-negative
      Enterobacteriales and Escherichia coli in colonic mucosa. Overall, our data
      indicate that the L. paracasei B21060 based synbiotic is effective in reducing
      the severity of liver injury and IR associated with high fat intake, suggesting
      its possible therapeutic/preventive clinical utilization. 

PMID- 24314868
TI  - Enhanced inhibition of prostate cancer xenograft tumor growth by combining
      quercetin and green tea.
AB  - The chemopreventive activity of green tea (GT) is limited by the low
      bioavailability and extensive methylation of GT polyphenols (GTPs) in vivo. We
      determined whether a methylation inhibitor quercetin (Q) will enhance the
      chemoprevention of prostate cancer in vivo. Androgen-sensitive LAPC-4 prostate
      cancer cells were injected subcutaneously into severe combined immunodeficiency
      (SCID) mice one week before the intervention. The concentration of GTPs in brewed
      tea administered as drinking water was 0.07% and Q was supplemented in diet at
      0.2% or 0.4%. After 6-weeks of intervention tumor growth was inhibited by 3%
      (0.2% Q), 15% (0.4% Q), 21% (GT), 28% (GT+0.2% Q) and 45% (GT+0.4% Q) compared to
      control. The concentration of non-methylated GTPs was significantly increased in
      tumor tissue with GT+0.4% Q treatment compared to GT alone, and was associated
      with a decreased protein expression of catechol-O-methyltransferase and multidrug
      resistance-associated protein (MRP)-1. The combination treatment was also
      associated with a significant increase in the inhibition of proliferation,
      androgen receptor and phosphatidylinositol 3-kinase/Akt signaling, and
      stimulation of apoptosis. The combined effect of GT+0.4% Q on tumor inhibition
      was further confirmed in another experiment where the intervention started prior
      to tumor inoculation. These results provide a novel regimen by combining GT and Q
      to improve chemoprevention in a non-toxic manner and warrant future studies in
      humans. 

PMID- 24314870
TI  - Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and
      differentiation.
AB  - Sarcopenia is a notable and debilitating age-associated condition. Flavonoids are
      known for their healthy effects and limited toxicity. The flavanol (-)
      epicatechin (Epi) enhances exercise capacity in mice, and Epi-rich cocoa improves
      skeletal muscle structure in heart failure patients. (-)-Epicatechin may thus
      hold promise as treatment for sarcopenia. We examined changes in protein levels
      of molecular modulators of growth and differentiation in young vs. old, human and
      mouse skeletal muscle. We report the effects of Epi in mice and the results of an
      initial proof-of-concept trial in humans, where muscle strength and levels of
      modulators of muscle growth were measured. In mice, myostatin and senescence
      associated beta-galactosidase levels increase with aging, while those of
      follistatin and Myf5 decrease. (-)-Epicatechin decreases myostatin and beta
      galactosidase and increases levels of markers of muscle growth. In humans,
      myostatin and beta-galactosidase increase with aging while follistatin, MyoD and
      myogenin decrease. Treatment for 7 days with (-)-epicatechin increases hand grip
      strength and the ratio of plasma follistatin/myostatin. In conclusion, aging has
      deleterious effects on modulators of muscle growth/differentiation, and the
      consumption of modest amounts of the flavanol (-)-epicatechin can partially
      reverse these changes. This flavanol warrants its comprehensive evaluation for
      the treatment of sarcopenia. 

PMID- 24314871
TI  - Assessment of quality of life and functional outcome in patients sustaining
      moderate and major trauma: a multicentre, prospective cohort study.
AB  - BACKGROUND: Trauma care systems aim to reduce both death and disability, yet
      there is little data on post-trauma health status and functional outcome.
      OBJECTIVES: To evaluate baseline, discharge, six month and 12 month post-trauma
      quality of life, functional outcome and predictors of quality of life in Hong
      Kong. METHODS: Multicentre, prospective cohort study using data from the trauma
      registries of three regional trauma centres in Hong Kong. Trauma patients with an
      ISS>=9 and aged>=18 years were included. The main outcome measures were the
      physical component summary (PCS) score and mental component summary (MCS) scores
      of the Short-Form 36 (SF36) for health status, and the extended Glasgow Outcome
      Scale (GOSE) for functional outcome. RESULTS: Between 1 January 2010 and 31
      September 2010, 400 patients (mean age 53.3 years; range 18-106; 69.5% male) were
      recruited to the study. There were no statistically significant differences in
      baseline characteristics between responders (N=177) and surviving non-responders
      (N=163). However, there were significant differences between these groups and the
      group of patients who died (N=60). Only 16/400 (4%) cases reported a GOSE>=7.
      62/400 (15.5%) responders reached the HK population norm for PCS. 125/400 (31%)
      responders reached the HK population norm for MCS. If non-responders had similar
      outcomes to responders, then the percentages for GOSE>=7 would rise from 4% to
      8%, for PCS from 15.5% to 30%, and for MCS from 31% to 60%. Univariate analysis
      showed that 12-month poor quality of life was significantly associated with
      age>65 years (OR 4.77), male gender (OR 0.44), pre-injury health problems (OR
      2.30), admission to ICU (OR 2.15), ISS score 26-40 (OR 3.72), baseline PCS (OR
      0.89), one-month PCS (OR 0.89), one-month MCS (OR 0.97), 6-month PCS (OR 0.76)
      and 6-month MCS (OR 0.97). CONCLUSION: For patients sustaining moderate or major
      trauma in Hong Kong at 12 months after injury<1 in 10 patients had an excellent
      recovery, <=3 in 10 reached a physical health status score>=Hong Kong norm,
      although as many as 6 in 10 patients had a mental health status score which
      is>=Hong Kong norm.

PMID- 24314872
TI  - Comparative study of comminuted posterior acetabular wall fracture treated with
      the Acetabular Tridimensional Memory Fixation System.
AB  - BACKGROUND: Posterior wall fractures are one of the most common acetabular
      fractures. However, only 30% of these fractures involve a single large fragment,
      and comminuted acetabular posterior wall fractures pose a particular surgical
      challenge. The purpose of this study was to compare outcomes between patients who
      received fixation for comminuted posterior wall fracture using the Acetabular
      Tridimensional Memory Fixation System (ATMFS) and patients who underwent fixation
      with conventional screws and buttress plates (Plates group). METHOD: Between
      April 2003 and May 2007, 196 consecutive patients who sustained a comminuted
      posterior wall fracture of acetabulum were treated with ATMFS or conventional
      screws and buttress plates. Operative time, fluoroscopy time, blood loss, and any
      intra-operative complications were recorded. Plain AP and lateral radiographs
      were obtained at all visits (Matta's criteria). Modified Merle d' Aubigne-Postel
      score, and Mos SF-36 score were compared between groups. RESULTS: Fifty patients
      were included in the analysis with 26 in the ATMFS group and 24 in the Plates
      group. The mean follow-up time was 57.5 months, ranging from 31 to 69 months. All
      patients had fully healed fractures at the final follow-up. There was no
      difference in clinical outcomes or radiological evaluations between groups.
      CONCLUSION: Patients with comminuted posterior wall fractures of the acetabulum
      treated with the ATMFS or conventional screws and buttress plate techniques
      achieve a good surgical result. Both techniques are safe, reliable, and
      practical. Use of the ATMFS technique may reduce blood loss and improve rigid
      support to marginal bone impaction. The use ATMFS may need additional support
      when fractures involve the superior roof.

PMID- 24314873
TI  - Time to pelvic embolization for hemodynamically unstable pelvic fractures may
      affect the survival for delays up to 60 min.
AB  - INTRODUCTION: We evaluated the relationship between survival and time from
      arrival to angiography for hemodynamically unstable patients with pelvic trauma.
      METHODS: A retrospective review of patients admitted to Fukui Prefectural
      Hospital with pelvic fractures during a 7.5-year period. Charts were reviewed for
      age, injury characteristics, injury severity score, systolic blood pressure and
      heart rate on arrival, base deficit, and the lactate concentration on arrival,
      transfusion requirement, fracture pattern, the time from hospital arrival to
      angiography, and the time spent in the angiography suite. RESULTS: Of a total of
      140 patients, 68 patients underwent pelvic angiography and embolization. Of the
      patients, 24 patients were hemodynamically unstable. The average injury severity
      score was 41.7. Of the patients, 17 had major ligamentous disruption. The average
      time from hospital arrival to angiography suite was 76 min. Of the
      hemodynamically unstable 24 patients, there were 12 deaths (50%). Patients who
      were embolized within 60 min of arrival had a significantly lower mortality rate
      (16 vs. 64%; p=0.04). There was no embolization-related complication and repeat
      angiography was not required in all patients. CONCLUSION: Earlier pelvic
      embolization within 60 min may affect the survival of hemodynamically unstable
      patients with pelvic fracture.

PMID- 24314874
TI  - Patellar tendon rerupture in a footballer: our personal surgical technique and
      review of the literature.
AB  - Patellar tendon rerupture is a relatively uncommon condition that severely
      compromises the function of the extensor mechanism of the knee. Few cases
      described in the literature does not show a unique mode of treatment for this
      type of lesion. We report the case of a young athlete with traumatic patellar
      tendon rerupture. The first rupture was treated with the use of Statak anchors.
      Following a second rerupture incident as a result of a sporting accodent, the
      tendon was reconstructed with the use of an autologous graft tendon of
      semitendinosus and biological augmentation with gracilis tendon. For both tendons
      the distal insertion part was preserved to facilitate the healing process. The
      treatment was completed with the application of a neutralization cerclage wire
      and with local injection of plateket reach plasma (PRP). At 12 months follow up,
      a full recovery of the structure and function of the extensor mechanism was
      observed and the patient was able to resume normal sports competitive activity. 

PMID- 24314875
TI  - Longitudinal relationship of diet and oxidative stress with depressive symptoms
      in patients with metabolic syndrome after following a weight loss treatment: the
      RESMENA project.
AB  - BACKGROUND & AIM: Metabolic syndrome and depression seem to share some common
      underlying mechanisms, although less is known about the impact of metabolic
      syndrome dietary treatments on depression. This study examined the association
      between a hypocaloric treatment designed to reduce metabolic syndrome features in
      self-perceived depression and the potential involvement of dietary components and
      oxidative stress changes. METHODS: Analyses were based on volunteers (n = 55)
      with metabolic syndrome (age 50 +/- 1 y.o.; 38M/17F), where depressive symptoms
      were assessed using the Beck Depression Inventory. Participants followed two
      hypocaloric diets (control diet and RESMENA diet) with the same energy
      restriction (-30% TCV) for six months. Depressive symptoms, dietary records,
      anthropometrical measurements, biochemical parameters and oxidative stress levels
      were analysed. RESULTS: Both diets improved self-perceived depression similarly
      (p = 0.528). Participants with lower depressive symptoms at baseline reported a
      significantly higher intake of omega-3 polyunsaturated fatty acids (p trend =
      0.002). Interestingly, after adjusting for potential confounders, the increase in
      folate consumption (p = 0.011) and the decrease in plasma malondialdehyde levels
      (p = 0.012) throughout the intervention, were associated with the improvement in
      depressive symptoms. CONCLUSIONS: A higher intake of folate and a decline in
      malondialdehyde plasma levels during a weight loss intervention, were related to
      improvements in manifestations of depression (www.clinicaltrials.gov;
      NCT01087086).

PMID- 24314876
TI  - An open-label study of anakinra for the treatment of moderate to severe
      hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder
      characterized by sterile abscesses and fistulae predominantly affecting the
      axillae and groin. Various biologic agents have been attempted for HS, but there
      is still no definitive treatment. OBJECTIVES: We sought to evaluate the efficacy,
      safety, and tolerability of anakinra in the treatment of moderate to severe HS.
      METHODS: Six patients with moderate to severe HS were enrolled in an open-label
      study with all patients receiving active treatment for 8 weeks with an additional
      8 weeks of follow-up off therapy. RESULTS: The 5 patients who completed the 8
      week therapy showed a significant mean decrease in their modified Sartorius score
      of 34.8 points. The physician and patient global assessment of overall activity
      showed significant reductions between baseline and 8 weeks of therapy: 45.8
      points and 35.6 points, respectively. The Dermatology Life Quality Index showed a
      significant reduction after 8 weeks of treatment with anakinra. Functional T-cell
      analysis revealed that patients had increased percentages of CD3(+) T cells in
      lesional skin compared with nonlesional skin before therapy. LIMITATIONS: The
      limited number of patients and lack of control group are limitations.
      CONCLUSIONS: Anakinra demonstrated decreased HS disease activity by both
      objective and subjective measures.

PMID- 24314877
TI  - Precursor B- or T-lymphoblastic lymphoma presenting with cutaneous involvement: a
      series of 13 cases including 7 cases of cutaneous T-lymphoblastic lymphoma.
AB  - BACKGROUND: Lymphoblastic lymphoma (LBL) is a rare neoplasm of precursor
      lymphocytes, and cutaneous involvement is present in less than 20% of cases.
      OBJECTIVE: We sought to describe the clinical and histopathological features of
      cutaneous LBL. METHODS: We retrospectively examined the clinical and histologic
      features of 13 patients with cutaneous LBL, 6 with B-LBL and 7 with T-LBL.
      RESULTS: Five of 6 patients with B-LBL had lesions in the head and neck area,
      whereas 4 of 7 patients with T-LBL developed skin lesions on sites other than the
      head and neck. Seven patients (1 case of B-LBL, and 6 of 7 cases of T-LBL)
      developed multiple skin lesions, and the T-LBL cases frequently developed
      multiple skin lesions in the head, neck, and throughout the torso. Complete
      remission was achieved in 9 patients (3 patients with T-LBL and all patients with
      B-LBL). LIMITATIONS: This study used a retrospective design and included a small
      sample size. CONCLUSION: This study compared the clinical features of T-LBL and B
      LBL, in particular the affected sites and number of skin lesions. Cutaneous T-LBL
      is likely to be accompanied by disseminated disease and has a relatively poor
      prognosis compared with B-LBL.

PMID- 24314878
TI  - Endovenous laser ablation of the great and short saphenous veins with a 1320-nm
      neodymium:yttrium-aluminum-garnet laser: retrospective case series of 1171
      procedures.
AB  - BACKGROUND: Venous insufficiency is a common medical condition affecting up to
      50.5% of women and 30.1% of men. Endovenous laser ablation is a minimally
      invasive procedure that safely and effectively treats reflux involving the great
      and short saphenous veins. OBJECTIVE: We sought to present safety and efficacy
      data of 1171 endovenous laser ablations using the Scripps Clinic endovenous laser
      therapy (EVLT) protocol. METHODS: We conducted an institutional review board
      approved, retrospective chart analysis of 1171 endovenous laser ablations
      performed from March 2007 until February 2011 treated at Scripps Clinic with the
      1320-nm neodymium:yttrium-aluminum-garnet laser with 1-month, 6-month, 1-year,
      and 2-year follow-up data. RESULTS: Our current overall experience is greater
      than 2000 EVLT procedures. The mean follow-up for this case series of 1171 EVLT
      procedures (1066 great saphenous veins and 105 short saphenous veins) is 11.4
      months with an overall closure success rate of 99.9% for patients not lost to
      follow-up. There has been no incidence of deep vein thrombosis, permanent nerve
      damage, or pulmonary embolism related to laser ablation. LIMITATIONS:
      Retrospective chart analysis, investigator bias, patients lost to follow-up, and
      lack of quality-of-life assessment are limitations. CONCLUSION: EVLT using a 1320
      nm neodymium:yttrium-aluminum-garnet laser appears to be a viable option for
      venous insufficiency and venous ulceration unresponsive to conservative
      treatment.

PMID- 24314879
TI  - National trends in utilization and outcomes of angioplasty and stenting for
      revascularization in intracranial stenosis.
AB  - INTRODUCTION: Angioplasty and intracranial stenting (ICS) are both endovascular
      revascularization procedures that have emerged as treatment options for
      intracranial atherosclerotic disease (ICAD). Some believe angioplasty alone is
      better, while others believe stenting is better. This study examines recent
      trends in utilization and outcomes of angioplasty alone and ICS in the United
      States using a population-based cohort. METHODS: The National Inpatient Sample
      (NIS) database was queried for patients with ICAD who underwent angioplasty or
      ICS from 2005 to 2010. RESULTS: There were 1115 patients (angioplasty: n=495,
      ICS: n=620) with ICAD who underwent endovascular revascularization. Over time,
      the number of endovascular revascularization procedures increased. The percentage
      of symptomatic patients (p=0.015) as well as in the number of comorbidities of
      patients treated (p<0.001) also increased. Combined post-procedure stroke and
      death rates were 16% and 28.9% for angioplasty and ICS, respectively (p<0.001). A
      larger percentage of angioplasty patients presented symptomatically compared to
      those who underwent ICS (p<0.001). CONCLUSION: Angioplasty appears to be
      associated with higher rates of peri-procedural complications; however, that may
      represent patient selection bias. Further studies are needed to identify patients
      who would benefit from revascularization and to clarify the roles of angioplasty
      and ICS.

PMID- 24314880
TI  - Purinergic receptor P2X7: a novel target for anti-inflammatory therapy.
AB  - Purinergic receptors, also known as purinoceptors, are ligand gated membrane ion
      channels involved in many cellular functions. Among all identified purinergic
      receptors, P2X7 subform is unique since it induces the caspase activity, cytokine
      secretion, and apoptosis. The distribution of P2X7 receptors, and the need of
      high concentration of ATP required to activate this receptor exhibited its
      ability to function as 'danger' sensor associated with tissue inflammation and
      damage. Further, the modulation of other signalling pathways associated with P2X7
      has also been proposed to play an important role in the control of macrophage
      functions and inflammatory responses, especially towards lipopolysaccharides.
      Experimentally, researchers have also observed the decreased severity of
      inflammatory responses in P2X7 receptor expressing gene (P2RX7) knockout (KO)
      phenotypes. Therefore, newly developed potent antagonists of P2X7 receptor would
      serve as novel therapeutic agents to combat various inflammatory conditions. In
      this review article, we tried to explore various aspects of P2X7 receptors
      including therapeutic potential, and recent discoveries and developments of P2X7
      receptor antagonists.

PMID- 24314881
TI  - Social networking as a learning tool: nursing students' perception of efficacy.
AB  - BACKGROUND: The pedagogical use of social networking technology in education is
      of growing interest to academics as a potential teaching and learning tool.
      However, the educational use of social networking sites such as Facebook is still
      under explored. Nursing students often perceive bioscience subjects as difficult
      and lack self-efficacy in their ability to be successful. In this case, as the
      final assessment for a bioscience related subject approached, students became
      increasingly anxious about their ability to perform in the assessment item. To
      better support students, a Facebook group was formed. OBJECTIVES: The aim of the
      study was to examine students' perceptions of the efficacy of using Facebook as a
      tool to support study. DESIGN: A convenience sample of BN students (n=533 across
      3 campuses), enrolled in the subject Medications and Safe Administration, were
      invited to join. 373 BN students joined the group (70% of the student cohort). A
      solution-focussed orientation underpinned the management of the group. METHODS: A
      descriptive, online survey was administered following release of students'
      results for the final assessment item to assess students' perceptions of how
      effective the group had been in helping them learn. The survey contained both
      quantitative and qualitative questions. Responses were received from 89 students
      (24%). Survey data were analysed descriptively and qualitative data were analysed
      thematically by the academic team. RESULTS: Students perceived the group to be an
      innovative method of study support that guided learning by enhancing self
      efficacy in their learning. Students also described how it was useful in
      promoting peer learning and engaging with academics. CONCLUSIONS: Social media
      platforms such as Facebook have the potential to enhance students' self-efficacy
      in learning and can support students to develop their learning to a deeper level.

PMID- 24314882
TI  - Thrombospondin-1-induced vascular smooth muscle cell migration and proliferation
      are functionally dependent on microRNA-21.
AB  - OBJECTIVES: Thrombospondin-1 (TSP-1) is a matricellular glycoprotein released
      from platelets at sites of arterial injury and is important in neointima
      development after balloon angioplasty. MicroRNAs are small noncoding RNAs that
      function by binding target gene mRNA and inhibiting protein translation. MicroRNA
      21 (miR-21) is up-regulated after angioplasty, and inhibition of miR-21 leads to
      decreased intimal hyperplasia. In this study, we examined the effects of miR-21
      inhibition on vascular smooth muscle cell (VSMC) processes. METHODS: VSMCs were
      exposed to TSP-1 and miR-21 inhibitor for 20 minutes. TSP-1-induced migration was
      assessed with a modified Boyden microchemotaxis chamber and proliferation with
      calcein-AM fluorescence. Phosphorylated extracellular signaling kinase (ERK) 1/2
      expression was determined by Western Blot and densitometry. Quantitative real
      time polymerase chain reaction for TSP-1, hyaluronic acid synthase 2 (HAS2), and
      transforming growth factor beta 2 (TGFbeta2) was performed. Statistical analysis
      was performed with analysis of variance (P < .05). RESULTS: Inhibition of miR-21
      blocked TSP-1-induced VSMC migration, proliferation, and ERK 1/2 phosphorylation
      (P < .05) and had no effect on TSP-1-stimulated expression of genes for TSP-1,
      HAS2, or TGFbeta2 (P > .05). CONCLUSION: Acute inhibition of miR-21 led to a
      decrease in VSMC migration and proliferation caused by TSP-1. The decrease in TSP
      1's activation of ERK 1/2 after acute miR-21 inhibition indicates an active role
      for miR-21 in TSP-1's cell signaling cascade. No effect on TSP-1-induced
      expression of the pro-stenotic genes thbs1, tgfb2, or has2, occurred after acute
      miR-21 inhibition. These data indicate that miR-21 directly modulates cell
      function and signaling pathways in ways other than inhibition of protein
      translation.

PMID- 24314883
TI  - Chemotherapy-associated liver injury and its influence on outcome after resection
      of colorectal liver metastases.
AB  - BACKGROUND: Advances in neoadjuvant therapy enabled novel strategies for treating
      resectable and initially unresectable colorectal cancer liver metastases.
      Although it is well known that chemotherapeutic agents cause certain types of
      liver parenchymal injury, the actual contribution of chemotherapy-associated
      hepatotoxicity to postoperative morbidity remains poorly defined. The aim of this
      study was to define all kinds of chemotherapy-associated liver injury and to
      examine its impact on postoperative morbidity. PATIENTS AND METHODS: We included
      119 patients who were treated between 2002 and 2010. Chemotherapy-associated
      changes of the liver were subclassified in 11 different categories and correlated
      with postoperative morbidity with the ultimate aim of generating a liver injury
      risk score. RESULTS: On univariate analysis severity (P = .004) and localization
      of parenchymal inflammation (P = .04) were associated with morbidity. Steatosis
      did not correlate with postoperative outcome (P = .69), whereas steatohepatitis
      (as assessed by the nonalcoholic fatty liver disease activity score score) was
      related with morbidity (P = .03). On multivariate analysis, the severity of
      inflammation (95% confidence interval, 1.008-6.526; odds ratio, 2.56; P = .04)
      was significantly correlated with postoperative morbidity. The newly developed
      liver injury risk score was highly associated with postoperative complications (P
      = .006). CONCLUSION: In this study, the induction of inflammation by conventional
      chemotherapy and its relevance for the development of clinical complications
      could be demonstrated. The proposed risk score for liver injury-related morbidity
      might help to better select patients eligible for an operation.

PMID- 24314884
TI  - Anatomic segmentectomy and brachytherapy mesh implantation for clinical stage I
      non-small cell lung cancer (NSCLC).
AB  - BACKGROUND: Sublobar wedge resection is associated with an increased risk of
      locoregional recurrence (15-20%) compared with lobectomy for early non-small cell
      lung cancer (NSCLC). We have previously shown that the addition of brachytherapy
      mesh at the time of sublobar resection might decrease the risk of local
      recurrence in this setting, equivalent to that of lobectomy [Santos et al.
      Surgery 2003;134:691-7]. In the current study, we evaluated the impact of
      brachytherapy mesh implantation after formal anatomic segmentectomy on local
      recurrence rates in the management of clinical stage I NSCLC. METHODS: We
      undertook a retrospective review of 369 patients undergoing anatomic
      segmentectomy for clinical stage I NSCLC from 2002 to 2010 with (n = 155) or
      without (n = 214) the use of I(131) brachytherapy mesh applied over the staple
      line. The primary end point was local recurrence. Secondary end points included
      morbidity, mortality, and recurrence-free survival. RESULTS: Patients undergoing
      brachytherapy mesh implantation were older (71.0 vs 69.0 years, P = .03) and had
      larger tumors (2.3 cm vs 2.0 cm, P = .001) compared with those treated without
      mesh. There were no differences noted in sex, histology, or tumor stage. Overall
      mortality was 1.1% (mesh, 0.6%; no mesh 1.4%). Perioperative morbidity was
      similar in patients receiving mesh (45.8% vs 37.4%, P = .11). At a mean follow-up
      of 32.9 months, the overall local recurrence rate was 5.4% (mesh: 6.4% vs no
      mesh: 4.6%, P = .49). Five-year actuarial freedom from local recurrence was 92%
      in the mesh group, and 90% in patients undergoing segmentectomy without mesh (P =
      .24). CONCLUSION: It appears that the local recurrence noted with non-anatomic
      wedge resection is not an equivalent concern when anatomic segmentectomy with
      adequate margins are obtained. This implies that adjuvant brachytherapy after
      anatomic segmentectomy is not required for local control, thus avoiding the costs
      of radiation therapy and its associated potential toxicity. These data also
      suggest that proper anatomic segmentectomy alone may be associated with local
      recurrence rates similar to those of anatomic lobectomy in the setting of
      clinical stage I NSCLC.

PMID- 24314885
TI  - Two lessons from a 5-year follow-up study of laparoscopic sleeve gastrectomy:
      persistent, relevant weight loss and a short surgical learning curve.
AB  - INTRODUCTION: Like Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy
      (LSG) has been validated as a bariatric surgery procedure in its own right.
      However, the few studies of the long-term outcomes of LSG have only featured
      small patient populations. The objective of the present study was to evaluate
      weight loss 5 years after LSG and assess the surgical learning curve for this
      procedure. METHODS: We performed a retrospective, single-center study of a
      prospective database including all consecutive patients having undergone LSG at
      Amiens University Medical Center between November 2004 and July 2007. Data
      (weight, body mass index [BMI], percentage of excess weight loss [EWL],
      percentage of excess BMI loss, and percentage weight loss [PWL]) were collected
      during follow-up (particularly after 5 years). RESULTS: The study population
      comprised 118 patients (100 females [85%]; mean +/- SD age, 40 +/- 11 years; mean
      preoperative weight, 131 +/- 22 kg; mean preoperative BMI, 47.7 +/- 7 kg/m(2)).
      LSG was performed after failure of gastric banding in 23 cases (19%) and after
      failure of an intragastric balloon in 1 (0.8%). In all, 95 patients (81%) were
      analyzed >=60 months after the LSG (mean follow-up period, 71 +/- 9 months). The
      PWL and EWL were 25 +/- 14% and 46 +/- 26%, respectively. Eleven patients had
      undergone a second bariatric operation within 5 years of the LSG. Concerning the
      84 patients in whom only LSG was the only operation, the PWL and EWL were 23 +/-
      14% and 43 +/- 25%, respectively. The EWL was >50% in 35 of these 84 patients
      (42%) and between 25 and 50% in 30 cases (36%). Optimal weight results were
      achieved after only 28 LSG had been performed, which testifies to a shorter
      learning curve than for most other bariatric surgery techniques. CONCLUSION:
      Isolated LSG is a quickly mastered bariatric surgery technique with a short
      learning curve. It enables a mean PWL of >25% and an EWL of >50% in >40% of
      cases.

PMID- 24314886
TI  - Antidepressants in older adults: complexities, confounds and clinical effects.

PMID- 24314888
TI  - Acute and long-term treatment of late-life major depressive disorder: duloxetine
      versus placebo.
AB  - OBJECTIVE: To compare the efficacy of duloxetine with placebo on depression in
      elderly patients with major depressive disorder. DESIGN: Multicenter, 24-week (12
      week short-term and 12-week continuation), randomized, placebo-controlled, double
      blind trial. SETTING: United States, France, Mexico, Puerto Rico. PARTICIPANTS:
      Age 65 years or more with major depressive disorder diagnosis (one or more
      previous episode); Mini-Mental State Examination score >=20; Montgomery-Asberg
      Depression Rating Scale total score >=20. INTERVENTION: Duloxetine 60 or 120
      mg/day or placebo; placebo rescue possible. MEASUREMENTS: Primary-Maier subscale
      of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary
      Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain
      Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression
      Severity scale, Patient Global Impression of Improvement in acute phase and acute
      plus continuation phase of treatment. RESULTS: Compared with placebo, duloxetine
      did not show significantly greater improvement from baseline on Maier subscale at
      12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and
      20. Similar patterns for Geriatric Depression Scale and Clinical Global
      Impression-Severity scale emerged, with significance also seen at week 24. There
      was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures
      in the acute phase, most BPI items and half of the NRS measures in the
      continuation phase. More duloxetine-treated patients completed the study (63%
      versus 55%). A significantly higher percentage of duloxetine-treated patients
      versus placebo discontinued due to adverse event (15.3% versus 5.8%).
      CONCLUSIONS: Although the antidepressant efficacy of duloxetine was not confirmed
      by the primary outcome, several secondary measures at multiple time points
      suggested efficacy. Duloxetine had significant and meaningful beneficial effects
      on pain.

PMID- 24314887
TI  - Is sertraline treatment or depression remission in depressed Alzheimer patients
      associated with improved caregiver well being? Depression in Alzheimer's Disease
      Study 2.
AB  - OBJECTIVE: We wanted to assess if sertraline treatment (versus placebo) or
      remission of depression at 12 weeks (versus nonremission) in Alzheimer patients
      is associated with improved caregiver well being. METHODS: We conducted a
      randomized, double-blind, placebo-controlled clinical trial of the efficacy and
      safety of sertraline for the treatment of depression in individuals with
      Alzheimer disease in five clinical research sites across the United States.
      Participants were caregivers of patients enrolled in the Depression in
      Alzheimer's Disease Study 2 (N = 131). All caregivers received standardized
      psychosocial support throughout the study. Caregiver outcome measures included
      depression (Beck Depression Inventory), distress (Neuropsychiatric Inventory),
      burden (Zarit Burden Interview), and quality of life (Medical Outcomes Study
      Short Form Health Survey). RESULTS: Fifty-nine percent of caregivers were
      spouses, 63.4% were women, and 64.1% were white. Caregivers of patients in both
      treatment groups had significant reductions in distress scores over the 24-week
      study period, but there was not a greater benefit for caregivers of patients
      taking sertraline. However, caregivers of patients whose depression was in
      remission at week 12 had greater declines in distress scores over the 24 weeks
      than caregivers of patients whose depression did not remit by week 12.
      CONCLUSION: Patient treatment with sertraline was not associated with
      significantly greater reductions in caregiver distress than placebo treatment.
      Distress but not level of depression or burden lessened for all caregivers
      regardless of remission status and even more so for those who cared for patients
      whose depression remitted. Results imply an interrelationship between caregiver
      distress and patient psychiatric outcomes.

PMID- 24314889
TI  - PTSD is a chronic, fluctuating disorder affecting the mental quality of life in
      older adults.
AB  - OBJECTIVES: Examine the longitudinal course of posttraumatic stress disorder
      (PTSD) in older adults and its influence on mental health quality of life
      (MHQoL). DESIGN: Evaluation performed at baseline, and 3 and 6 months
      postrandomization as part of a longitudinal trial. PARTICIPANTS AND SETTINGS: A
      total of 1,185 participants, with a mean (+/-SD) age of 73.53 (+/-5.98) years, at
      seven primary care sites (including five Veterans Affairs clinics), were divided
      into four groups, namely, no trauma (n = 661), trauma only (n = 319), partial
      PTSD (n = 114), and PTSD (n = 81), based on reports of trauma and associated PTSD
      symptoms. MEASUREMENTS: The prevalence of comorbid depression, anxiety, and
      alcohol use disorders, assessed using the Diagnostic and Statistical Manual,
      Fourth Edition, criteria and changes in MHQoL, as assessed by the Short Form-36
      mental component score. RESULTS: At baseline, the PTSD group had higher
      frequencies of comorbid depression and anxiety disorders and worse MHQoL than the
      other groups. Both chronic (participants diagnosed with PTSD at all three
      assessments) and fluctuating (participants moving to or from one of the other
      groups) trajectories of course were observed during the follow-up period, which
      appeared to be separate from that of the comorbid disorders. Even after
      accounting for those comorbid disorders, PTSD had an independent association with
      poorer MHQoL at multiple time points, especially in men, whereas trauma without
      PTSD symptoms (trauma only) had better MHQoL. CONCLUSIONS: PTSD had chronic and
      fluctuating courses, with negative effects on MHQoL, while partial PTSD might
      represent a transitional state, underscoring the need to better identify and
      treat PTSD at any phase in later life.

PMID- 24314890
TI  - Acute hepatitis C with evidence of heterosexual transmission: a new case.

PMID- 24314891
TI  - Detection of antibiotic residues and association of cefquinome residues with the
      occurrence of Extended-Spectrum beta-Lactamase (ESBL)-producing bacteria in waste
      milk samples from dairy farms in England and Wales in 2011.
AB  - Waste milk samples from 103 farms in England and Wales were examined for the
      presence of beta-lactam antibiotics and ESBL-producing Enterobacteriaceae.
      Approximately 10 months after the initial sampling, further waste milk,
      environmental and faecal samples from farms shown to be positive for CTX-M
      Escherichia coli were investigated further. Isolates with an ESBL phenotype were
      tested by PCR for the presence of blaCTX-M, blaOXA, blaSHV and blaTEM genes.
      Isolates positive for blaCTX-M were sequenced to determine CTX-M type.
      Representative isolates were further examined by PFGE, plasmid replicon typing
      and serotyping. Of particular interest, 21.4% of waste milk samples contained
      residues of the cephalosporin cefquinome, which was significantly associated with
      CTX-M bacteria. Such bacteria occurred in 5.8% of the waste milk samples
      (including 3.9% CTX-M E. coli). CTX-M types identified were 1, 14, 14b and 15,
      but none of the E. coli were serotype O25, the serotype of the human pandemic
      strain.

PMID- 24314892
TI  - Psoriasis in pregnancy: a review (II).
AB  - Scarce scientific evidence is available to define the precise effects that
      certain drugs might have on embryonic and fetal development if taken by pregnant
      women with psoriasis, given the ethical concerns that preclude enrolling such
      women in clinical trials. The little information on the use of biologics during
      gestation that has been published is based on retrospective and observational
      studies, and experience with these drugs in this context in psoriasis is still
      very limited. The literature seems to suggest that biologic therapy is safe
      during pregnancy, but there is no certainty. This detailed review of accumulated
      experience with biologic therapy during pregnancy relies mainly on descriptions
      of the management of other types of rheumatic disease, although the use of these
      agents in psoriasis is growing steadily. 

PMID- 24314893
TI  - Are nuclear medicine residents prepared for employment? A survey-informed
      perspective.

PMID- 24314894
TI  - Bronchial haemangioma: exceptionally rare cause of haemoptysis.
AB  - Bronchial haemangioma is an exceptionally rare cause of haemoptysis in the adult.
      There are currently less than 10 recorded cases in the literature. Airway
      haemangiomas are generally seen in infants with coexistent cutaneous
      haemangiomas. The incidence of bronchial haemangioma in adults remains unknown.
      This case reports the diagnosis and treatment of a bronchial haemangioma in a 56
      year-old male presenting with a one-month history of haemoptysis. Bronchial
      haemangioma diagnosis was confirmed and excision performed by bronchoscopy
      without complication. Bronchial haemangioma should be a considered differential
      diagnosis in the presence of meaningful haemoptysis when an endoluminal lesion is
      visualised on computed tomography scan. This case also demonstrates that
      bronchial haemangiomas can be successfully removed via bronchoscopy with minimal
      risk and discomfort to the patient. 

PMID- 24314895
TI  - 'Early' post-cardiotomy chylopericardium and the imaging value of magnetic
      resonance thoracic-ductography.
AB  - Isolated chylopericardium is a rare postoperative complication after cardiac
      surgery. A delay in diagnosis or an inappropriate management can lead to serious
      consequences. The treatment, which may either be conservative or surgical, is
      controversial and it depends on the duration and volume of effusion. We report a
      case of chylopericardium after atrial septal defect repair in a young woman. The
      patient was treated initially with total parenteral nutrition for 10 days. After
      drainage diminished, low fat diet containing medium chain triglyceride was
      instituted. Postoperatively, the role of magnetic resonance thoracic ductography
      was important for the assessment of the treatment strategy. 

PMID- 24314896
TI  - Measuring real-time concentration trends of individual VOC in an elementary
      school using a sub-ppb detection MUGC and a single GC-MS analysis.
AB  - This paper reports the results from a field study that used a micro gas
      chromatograph (MUGC) in conjunction with single gas chromatography-mass
      spectrometry (GC-MS) analysis to obtain the time-dependent concentration changes
      of individual volatile organic compounds (VOCs). The MUGC is capable of
      performing sub-ppb analysis every 15min and has a total weight of only 3kg, which
      includes an embedded tablet computer. The field study was conducted in an
      elementary school near a chemical industrial area. Six VOCs including acetone, 2
      butanone, methyl acetate, toluene, m-xylene and isobutyl acetate, were detected
      at low ppb levels via canister/GC-MS analysis. Five of the six chemicals were
      successfully quantified using the MUGC. The lone exception was acetone, which
      prematurely breakthrough on the preconcentrator of the MUGC because of its high
      volatility. The continuous analyses performed by the MUGC revealed the individual
      temporal trends of the concentrations for the remaining 5 chemicals. The
      establishment of real-time trends for each of the chemicals enabled a detailed
      examination of their correlations. 

PMID- 24314897
TI  - Enhancement of Cd phytoextraction by two Amaranthus species with endophytic
      Rahnella sp. JN27.
AB  - Microbe-assisted phytoextraction shows a potential for the remediation of metal
      contaminated soils. The aim of this study was to isolate, characterize, and
      evaluate the potential of endophytic bacteria in improving plant growth and metal
      uptake by Cd-hyperaccumulators-Amaranthus hypochondriacus and Amaranthus
      mangostanus. An endophytic bacterial strain JN27 isolated from roots of Zea mays
      displayed high tolerance and mobilization to Cd, and was identified as Rahnella
      sp. based on 16S rDNA sequencing. The strain also exhibited multiple plant growth
      beneficial features including the production of indole-3-acetic acid,
      siderophore, 1-aminocyclopropane-1-carboxylic acid deaminase and solubilization
      of insoluble phosphate. Subsequently, a pot trial was performed to elucidate the
      effects of inoculation with JN27 on plant growth and Cd uptake by A.
      hypochondriacus, A. mangostanus, Solanum nigrum and Z. mays grown in soils with
      different levels of Cd (25, 50, 100 mg Cd kg(-1)). The results revealed that
      inoculation with JN27 significantly increased the biomasses of all the tested
      plants and the Cd concentrations of all the tested plants except Z. mays in both
      above-ground and root tissues. Moreover, strain JN27 could successfully re
      colonized in rhizosphere soils of all the tested plants and root interior of A.
      hypochondriacus and Z. mays. The present results indicated that the symbiont of
      A. hypochondriacus (or A. mangostanus) and strain JN27 can effectively improve
      the Cd uptake by plants and would be a new strategy in microbe-assisted
      phytoextraction for metal-contaminated soils.

PMID- 24314898
TI  - Bridging the gap between life cycle inventory and impact assessment for
      toxicological assessments of pesticides used in crop production.
AB  - In Life Cycle Assessment (LCA), the Life Cycle Inventory (LCI) provides emission
      data to the various environmental compartments and Life Cycle Impact Assessment
      (LCIA) determines the final distribution, fate and effects. Due to the overlap
      between the Technosphere (anthropogenic system) and Ecosphere (environment) in
      agricultural case studies, it is, however, complicated to establish what LCI
      needs to capture and where LCIA takes over. This paper aims to provide guidance
      and improvements of LCI/LCIA boundary definitions, in the dimensions of space and
      time. For this, a literature review was conducted to provide a clear overview of
      available methods and models for both LCI and LCIA regarding toxicological
      assessments of pesticides used in crop production. Guidelines are provided to
      overcome the gaps between LCI and LCIA modeling, and prevent the overlaps in
      their respective operational spheres. The proposed framework provides a starting
      point for LCA practitioners to gather the right data and use the proper models to
      include all relevant emission and exposure routes where possible. It is also able
      to predict a clear distinction between efficient and inefficient management
      practices (e.g. using different application rates, washing and rinsing
      management, etc.). By applying this framework for toxicological assessments of
      pesticides, LCI and LCIA can be directly linked, removing any overlaps or gaps in
      between the two distinct LCA steps. 

PMID- 24314899
TI  - Ondansetron and the risk of cardiac arrhythmias: a systematic review and
      postmarketing analysis.
AB  - STUDY OBJECTIVE: To explore the risk of cardiac arrhythmias associated with
      ondansetron administration in the context of recent recommendations for
      identification of high-risk individuals. METHODS: We conducted a postmarketing
      analysis and systematically reviewed the published literature, grey literature,
      manufacturer's database, Food and Drug Administration Adverse Events Reporting
      System, and the World Health Organization Individual Safety Case Reports Database
      (VigiBase). Eligible cases described a documented (or perceived) arrhythmia
      within 24 hours of ondansetron administration. The primary outcome was arrhythmia
      occurrence temporally associated with the administration of a single, oral
      ondansetron dose. Secondary objectives included identifying all cases associating
      ondansetron administration (any dose, frequency, or route) to an arrhythmia.
      RESULTS: Primary: No reports describing an arrhythmia associated with single oral
      ondansetron dose administration were identified. Secondary: Sixty unique reports
      were identified. Route of administration was predominantly intravenous (80%). A
      significant medical history (67%) or concomitant use of a QT-prolonging
      medication (67%) was identified in 83% of reports. Approximately one third
      occurred in patients receiving chemotherapeutic agents, many of which are known
      to prolong the QT interval. An additional third involved administration to
      prevent postoperative vomiting. CONCLUSION: Current evidence does not support
      routine ECG and electrolyte screening before single oral ondansetron dose
      administration to individuals without known risk factors. Screening should be
      targeted to high-risk patients and those receiving ondansetron intravenously.

PMID- 24314901
TI  - Does active chest compression-decompression cardiopulmonary resuscitation
      decrease mortality, neurologic impairment, or cardiopulmonary resuscitation
      related complications after cardiac arrest?

PMID- 24314900
TI  - Derivation of a clinical decision instrument to identify adult patients with mild
      traumatic intracranial hemorrhage at low risk for requiring ICU admission.
AB  - STUDY OBJECTIVE: The objective of this study is to derive a clinical decision
      instrument with a sensitivity of at least 95% (with upper and lower bounds of the
      95% confidence intervals [CIs] within a 5% range) to identify adult emergency
      department patients with mild traumatic intracranial hemorrhage who are at low
      risk for requiring critical care resources during hospitalization and thus may
      not need admission to the ICU. METHODS: This was a prospective, observational
      study of adult patients with mild traumatic intracranial hemorrhage (initial
      Glasgow Coma Scale [GCS] score 13 to 15, with traumatic intracranial hemorrhage)
      presenting to a Level I trauma center from July 2009 to February 2013. The need
      for ICU admission was defined as the presence of an acute critical care
      intervention (intubation, neurosurgical intervention, blood product transfusion,
      vasopressor or inotrope administration, invasive monitoring for hemodynamic
      instability, urgent treatment for arrhythmia or cardiopulmonary resuscitation,
      and therapeutic angiography). We derived the clinical decision instrument with
      binary recursive partitioning (with a misclassification cost of 20 to 1). The
      accuracy of the decision instrument was compared with the treating physician's
      (emergency medicine faculty) clinical impression. RESULTS: A total of 600
      patients with mild traumatic intracranial hemorrhage were enrolled; 116 patients
      (19%) had a critical care intervention. The derived instrument consisted of 4
      predictor variables: admission GCS score less than 15, nonisolated head injury,
      aged 65 years or older, and evidence of swelling or shift on initial cranial
      computed tomography scan. The decision instrument identified 114 of 116 patients
      requiring an acute critical care intervention (sensitivity 98.3%; 95% CI 93.9% to
      99.5%) if at least 1 variable was present and 192 of 484 patients who did not
      have an acute critical care intervention (specificity 39.7%; 95% CI 35.4% to
      44.1%) if no variables were present. Physician clinical impression was slightly
      less sensitive (90.1%; 95% CI 83.1% to 94.4%) but overall similar to the clinical
      decision instrument. CONCLUSION: We derived a clinical decision instrument that
      identifies a subset of patients with mild traumatic intracranial hemorrhage who
      are at low risk for acute critical care intervention and thus may not require ICU
      admission. Physician clinical impression had test characteristics similar to
      those of the decision instrument. Because the results are based on single-center
      data without a validation cohort, external validation is required.

PMID- 24314902
TI  - Clinical outcomes of everolimus- and zotarolimus-eluting stents in patients with
      acute myocardial infarction for small coronary artery disease.
AB  - BACKGROUND AND PURPOSE: There were limited data about comparison of zotarolimus
      eluting stents (ZES) and everolimus-eluting stents (EES) in patients with small
      coronary artery disease (CAD), especially in patients with acute myocardial
      infarction (AMI). The objective of this study was to compare the clinical
      outcomes of ZES and EES in patients with AMI for small CAD. METHODS AND SUBJECTS:
      A total 1565 AMI patients treated with Endeavor-ZES (n=651) (Medtronic
      CardioVascular, Santa Rosa, CA, USA) or Xience V/Promus-EES (n=914) (Abbott
      Vascular, Temecula, CA/Boston Scientific, Natick, MA, USA) for small CAD (stent
      diameter <= 2.75 mm) in KAMIR (Korea Acute Myocardial Infarction Registry) were
      enrolled. After propensity score matching to adjust for baseline clinical and
      angiographic characteristics, we compared a total 1302 patients (651 ZES and 651
      EES) about major adverse cardiac events (MACE) at 1-year. Subgroup analysis about
      1-year clinical outcomes was undertaken in patients who were discharged alive.
      RESULTS: Baseline clinical and angiographic characteristics were similar between
      the two groups after propensity score matching. Total MACE did not differ between
      the two groups before (9.8% vs. 8.2%, p=0.265) and after (9.8% vs. 9.4%, p=0.778)
      propensity score matching. The EES group showed lower rate of 1-year cardiac
      death (5.4% vs. 3.3%, p=0.041), target lesion failure (TLF; 6.9% vs. 4.3%,
      p=0.022), and stent thrombosis (1.4% vs. 0.4%, p=0.042) compared with the ZES
      group. However, there were no differences in 1-year cardiac death, TLF, and stent
      thrombosis in propensity score matched populations. Other various 1-year clinical
      outcomes showed no difference between the two groups. Subgroup analysis in
      patients who were discharged alive showed similar outcomes between the two groups
      at 1-year follow-up. CONCLUSION: In-this propensity score matched analysis, EES
      and ZES showed no significant difference in clinical outcomes at 1-year follow-up
      in patients with AMI for small CAD.

PMID- 24314903
TI  - Effect of long-term orthotic treatment on gait biomechanics in adolescent
      idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: A previous study showed subtle biomechanical changes in the
      gait of unbraced adolescent idiopathic scoliosis (AIS) patients such as a
      reduction of pelvic, hip, knee, and ankle displacements. However, lumbopelvic
      muscles' timing activity was bilaterally increased during gait and correlated to
      excessive oxygen consumption as compared with healthy subjects. Usually, a brace,
      when indicated, is worn strictly for 22 hours every day in skeletally immature
      idiopathic scoliotic girls. To our knowledge, no study has assessed the long-term
      brace effect (6 months) on functional activities such as level walking. PURPOSE:
      To assess the stiffening effects of 6 months' brace wearing on instrumented gait
      analysis in girls with thoracolumbar/lumbar adolescent idiopathic scoliosis.
      STUDY DESIGN/SETTING: Clinical prospective study. PATIENT SAMPLE: Thirteen girls
      diagnosed as progressive adolescent idiopathic scoliosis with left
      thoracolumbar/lumbar curves (curves ranging 25 degrees -40 degrees ). OUTCOME
      MEASURES: All patients underwent a radiographic and instrumented gait analysis,
      including assessment of kinematics, mechanics, electromyography (EMG), and
      energetics of walking. METHODS: The scoliotic girls were prospectively studied at
      S1 (before bracing) and 6 months later at S2 (out-brace: treatment effect). The
      gait parameters were compared with those of 13 matched healthy girls. A t paired
      test was conducted to evaluate the effect of the 6-month orthotic treatment in
      AIS girls. Student t test was performed to compare the scoliotic group at S2 and
      the healthy subjects to identify if the observed changes in gait parameters meant
      improvement or worsening of gait. RESULTS: After 6 months of orthotic treatment
      in AIS, thoracolumbar/lumbar curves and apical rotation remained reduced by 25%
      and 61%, respectively. During gait, frontal pelvis and hip motions were
      significantly increased. Muscular mechanical work increased becoming closer but
      still different as compared with healthy subjects. Bilateral lumbopelvic muscles
      were almost 40% more active in AIS at S1 compared with healthy subjects and did
      not change at S2 except for the erector spinae muscles EMG activity, which
      decreased significantly. Energy cost exceeded by 30% in AIS at S1 compared with
      healthy subjects and did not change at 6 months' follow-up. CONCLUSIONS: After 6
      months of orthotic treatment, in an out-brace situation, the main structural
      thoracolumbar/lumbar curve remained partly corrected. Frontal pelvis and hip
      motion increased, contributing to an improvement of muscular mechanical work
      during walking. EMG activity duration of lumbopelvic muscles did not change
      except for the erector spinae muscles, which was decreased but without any
      beneficial change in the energy cost of walking. In summary, brace treatment,
      after 6 months, did not significantly influence the gait variables in AIS girls
      deleteriously, but did not reduce the excessive energy cost, which was 30% above
      the values of normal adolescents.

PMID- 24314904
TI  - Anatomic radiological variations in developmental lumbar spinal stenosis: a
      prospective, control-matched comparative analysis.
AB  - BACKGROUND CONTEXT: Developmental lumbar spinal stenosis is a maldevelopment of
      the dorsal spinal elements involving short pedicles and a trefoil bony spinal
      canal that increases the likelihood of neural compression at an earlier age.
      PURPOSE: To identify radiographically the anatomic variations caused by the
      maldevelopment of the infrequently characterized dorsal spinal elements. STUDY
      DESIGN: A prospective, control-matched comparative analysis. METHODS: Magnetic
      resonance imaging (MRI) and anteroposterior (AP) plain radiographs of 66 patients
      (mean age, 40.7 years) selected and randomized prospectively and compared with
      images of 45, age- and gender-matched control subjects. Variables assessed
      included spinal canal cross-sectional area (CSA), thecal sac AP and transverse
      canal diameters (CSA), and interpedicular distance. All were expressed in ratios
      with vertebral body diameter (VBD), interlaminar angle, stenosis grade, and MRI
      evidence of disc degeneration. RESULTS: In the stenosis cohort, global pathology
      and multilevel involvement with L3, L4, and L5 segments were involved more
      commonly and severely. Severe stenosis, at L1, L2, and S1 occurs infrequently.
      Multivariate analysis demonstrated a statistically significant reduction in
      spinal canal CSA-to-vertebral body CSA ratio, AP spinal canal diameter-to-VBD
      ratio on axial and sagittal magnetic resonance images, and plain radiograph
      interpedicular distance-to-VBD ratio at all levels. Interlaminar angle and the
      transverse spinal canal diameter-to-VBD ratio were reduced significantly in the
      stenosed cohort at all levels, except L1. No statistically significant difference
      regarding the incidence of disc degeneration on MRI between the two cohorts, as
      well as thecal sac CSA-to-spinal canal CSA ratios across all levels were
      observed, except for L3 and S1 (p<.05). CONCLUSIONS: Three spinal canal
      morphologies were identified: (1) "flattened" canal with predominantly reduced
      spinal canal AP diameter, (2) spinal canal with predominantly reduced
      interlaminar angle, and (3) global reduction of all canal parameters. Early age
      at presentation and subtle spondylosis, although typical, should not be
      considered the identifying, differentiating factors.

PMID- 24314905
TI  - Fat embolism syndrome following percutaneous vertebroplasty: a case report.
AB  - BACKGROUND CONTEXT: Vertebroplasty is commonly performed for management of pain
      associated with vertebral compression fractures. There have been two previous
      reports of fatal fat embolism following vertebroplasty. Here we describe a case
      of fat embolism syndrome following this procedure, and also provide fluoroscopic
      video evidence consistent with this occurrence. PURPOSE: The purpose of this
      study was to review the literature and report a case of fat embolism syndrome in
      a patient who underwent percutaneous vertebroplasty for compression fracture.
      STUDY DESIGN/SETTING: The study design for this manuscript was of a clinical case
      report. METHODS: A 68-year-old woman who developed sudden back pain with minimal
      trauma was found to have a T6 vertebral compression fracture on radiographs and
      bone scans. Percutaneous vertebroplasty of T5 and T6 was performed. RESULTS:
      Fluoroscopic imaging during the procedure demonstrated compression and
      rarefaction of the fractured vertebra associated with changes in intrathoracic
      pressure. Immediately after the procedure, the patient's back pain resolved and
      she was discharged home. Two days later, she developed increasing respiratory
      distress, confusion, and chest pain. A petechial rash on her upper arms also
      appeared. No evidence of bone cement leakage or pulmonary filling defects were
      seen on computed tomography-pulmonary angiography. Brain magnetic resonance
      imaging demonstrated hyperintensities in the periventricular and subcortical
      white matter on T2/fluid-attenuated inversion recovery sequences. A diagnosis of
      fat embolism syndrome was made, and the patient recovered with conservative
      management. CONCLUSIONS: Percutaneous vertebroplasty is a relatively safe and
      simple procedure, reducing pain and improving functional limitations in patients
      with vertebral fractures. This case demonstrates an uncommon yet serious
      complication of fat embolism syndrome. Clinicians must be aware of this
      complication when explaining the procedure to patients and provide prompt
      supportive care when it does occur.

PMID- 24314906
TI  - Verification of measurements of lumbar spinal dimensions in T1- and T2-weighted
      magnetic resonance imaging sequences.
AB  - BACKGROUND CONTEXT: Magnetic resonance imaging (MRI) is commonly used to assess
      patients with lumbar spinal stenosis. No single MRI sequence has been shown to be
      superior in spinal canal measurements. There are also cost concerns for the
      increased clinical and research use of MRI. Using only a single sequence may
      lower the financial burden; however, this requires spinal canal measurements in
      both T1 and T2 MRI to be reliable. Evidence for this is currently lacking.
      PURPOSE: The aim of this study was to determine the intra- and inter-reader
      reliability of MRI measurements of the lumbar spine and the reliability of
      measurements using T1- and T2-weighted MRI films. STUDY DESIGN/SETTING:
      Retrospective study. PATIENT SAMPLE: Forty-two randomly selected patients who
      underwent spinal stenosis surgery. OUTCOME MEASURES: Lumbar spinal canal
      measurements and reliability analysis between T1- and T2-weighted MRI. METHODS:
      Qualitative ratings of MRI features were performed according to previously
      published criteria by 2 independent readers (JP-YC, HS). Measurements in axial
      scan included midline anteroposterior (AP) vertebral body diameter, midvertebral
      body width, midline AP spinal canal diameter, midline AP dural sac diameter,
      spinal canal width/interpedicular distance, pedicle width (right and left), and
      lamina angle. Measurements in the sagittal scan included midline AP body
      diameter, midvertebral body height, and AP spinal canal diameter. Cronbach alpha
      was used to characterize intra- and inter-reader reliability for qualitative
      rating data. Similarly, T1 and T2 comparison also was performed in the same
      manner. RESULTS: Good to excellent intra- and interobserver reliability was
      obtained for all measurements. Reliability analysis of all T1 and T2 measurements
      was excellent. CONCLUSIONS: Either T1 or T2 images can be used for measurements
      of spinal canal dimensions. These findings are of importance, as not every
      patient undergoing preoperative MRI assessment will necessarily have both
      sequences performed and only a single sequence is required for research studies.
      Our findings are also of relevance in measurement of lumbar canal diameters.

PMID- 24314907
TI  - Disrupted action monitoring in recent-onset psychosis patients with schizophrenia
      and bipolar disorder.
AB  - Schizophrenia patients experience cognitive control disturbances, manifest in
      altered neural signatures during action monitoring. It remains unclear whether
      error- and conflict-monitoring disturbances co-occur, and whether they are
      observed in recent-onset psychosis patients with schizophrenia or bipolar
      disorder. We tested electrophysiological measures of action monitoring in these
      patients. Seventy-three schizophrenia patients (SZ), 26 bipolar disorder type I
      patients (BP), each within one year of psychosis onset, and 54 healthy control
      subjects (HC) underwent EEG during Stroop task performance. In the trial-averaged
      EEG at three midline scalp electrodes, the error-related negativity (ERN), error
      positivity (Pe) and conflict-related N450 were measured. Compared to HC (1) SZ
      exhibited an attenuated ERN and N450, and Pe unchanged and (2) BP exhibited an
      attenuated ERN but normal Pe and N450. Between patient groups, SZ showed an
      attenuated N450; ERN and Pe were not significantly different. A small (n=10) SZ
      subgroup that was not receiving antipsychotic medication showed normal ERPs.
      Altered error- and conflict-monitoring occur together in the first-episode
      schizophrenia patients, and these measures are comparable in patients with the
      first-episode bipolar disorder. Antipsychotic medication may be associated with
      altered measures of error-monitoring in schizophrenia. 

PMID- 24314908
TI  - Dopamine transporter dysfunction in Han Chinese people with chronic
      methamphetamine dependence after a short-term abstinence.
AB  - Single-photon emission-computed tomography (SPECT) after the administration of
      (99m)Tc-TRODAT-1 was performed on healthy subjects and subjects with
      methamphetamine (METH)dependence at time 1 (T1) after 24-48 h of abstinence, time
      2 (T2) after 2 weeks of abstinence, and time 3 (T3) after 4 weeks of abstinence.
      In contrast to values in controls, the values of the striatal DAT specific uptake
      ratios (SURs) in subjects with METH dependence were significantly lower at T1
      (n=25), T2 (n=9), and T3 (n=8); a mild increase in SURs was observed at T2 and
      T3, but values were still significantly lower than those in controls. In subjects
      with METH dependence, there was a trend for a negative correlation of striatal
      DAT SURs and craving for METH at T1. METH craving, anxiety and depression scores
      significantly decreased from T1 to T2 to T3. We conclude that Han Chinese people
      with METH dependence experience significant striatal DAT dysfunction, and that
      these changes may be mildly reversible after 4 weeks of abstinence, but that DAT
      levels still remain significantly lower than those in healthy subjects. The mild
      recovery of striatal DAT may parallel improvements in craving, anxiety and
      depression.

PMID- 24314910
TI  - Provision of medical abortion using telemedicine in Brazil.
AB  - OBJECTIVE: To evaluate the need for and outcome of self-administered medical
      abortion with mifepristone and misoprostol in Brazil, provided through Women on
      Web, a global telemedicine abortion service. STUDY DESIGN: A retrospective case
      review of women from Brazil who contacted Women on Web in 2011. Information from
      the online consultation, follow-up questionnaire and emails were used to analyze
      data including demographics, gestational age, outcome of the medical abortion and
      symptoms that lead to surgical interventions. RESULTS: The Women on Web website
      had 109779 unique visitors from Brazil, 2104 women contacted the helpdesk by
      email. Of the 1401 women who completed the online consultation, 602 women
      continued their request for a medical abortion. Of the 370 women who used the
      medicines, 307 women gave follow-up information about the outcome of the medical
      abortion. Of these, 207 (67.4%) women were 9 weeks or less pregnant, 71 (23.1%)
      were 10, 11 or 12 weeks pregnant, and 29 (9.5%) women were 13 weeks or more
      pregnant. There was a significant difference in surgical intervention rates after
      the medical abortion (19.3% at <9 weeks, 15.5% at 11-12 weeks and 44.8% at >13
      weeks, p=.06). However, 42.2% of the women who had a surgical intervention had no
      symptoms of a complication. CONCLUSION: There is large need for medical abortion
      in Brazil. Home use of mifepristone and misoprostol provided through telemedicine
      is safe and effective. However, after 13 weeks gestation, there is an increased
      risk of surgical intervention that may be due to the regimen used and local
      clinical practices in Brazil. IMPLICATIONS: The current study shows that there is
      an unmet need for medical abortion in Brazil, a country with legal restrictions
      on access to safe abortion services. Telemedicine can help fulfill the need and
      self administration of medical abortion is safe and effective even at late first
      trimester abortion. Prospective trials are needed to establish safety,
      effectiveness and acceptability of home use of medical abortion beyond 12 weeks
      of pregnancy.

PMID- 24314909
TI  - Characterizing the mechanisms of central and peripheral forms of neurostimulation
      in chronic dysphagic stroke patients.
AB  - BACKGROUND: Swallowing problems following stroke may result in increased risk of
      aspiration pneumonia, malnutrition, and dehydration. OBJECTIVE/HYPOTHESIS: Our
      hypothesis was that three neurostimulation techniques would produce beneficial
      effects on chronic dysphagia following stroke through a common brain mechanism
      that would predict behavioral response. METHODS: In 18 dysphagic stroke patients
      (mean age: 66 +/- 3 years, 3 female, time-post-stroke: 63 +/- 15 weeks [+/-SD]),
      pharyngeal electromyographic responses were recorded after single-pulse
      transcranial magnetic stimulation (TMS) over the pharyngeal motor cortex, to
      measure corticobulbar excitability before, immediately, and 30 min, after real
      and sham applications of neurostimulation. Patients were randomized to a single
      session of either: pharyngeal electrical stimulation (PES), paired associative
      stimulation (PAS) or repetitive TMS (rTMS). Penetration-aspiration scores and
      bolus transfer timings were assessed before and after both real and sham
      interventions using videofluoroscopy. RESULTS: Corticobulbar excitability of
      pharyngeal motor cortex was beneficially modulated by PES, PAS and to a lesser
      extent by rTMS, with functionally relevant changes in the unaffected hemisphere.
      Following combining the results of real neurostimulation, an overall increase in
      corticobulbar excitability in the unaffected hemisphere (P = .005, F1,17 = 10.6,
      ANOVA) with an associated 15% reduction in aspiration (P = .005, z = -2.79) was
      observed compared to sham. CONCLUSIONS: In this mechanistic study, an increase in
      corticobulbar excitability the unaffected projection was correlated with the
      improvement in swallowing safety (P = .001, rho = -.732), but modality-specific
      differences were observed. Paradigms providing peripheral input favored change in
      neurophysiological and behavioral outcome measures in chronic dysphagia patients.
      Further larger cohort studies of neurostimulation in chronic dysphagic stroke are
      imperative.

PMID- 24314911
TI  - Effect of lubricants and a vaginal spermicide gel on the detection of prostate
      specific antigen, a biomarker of semen exposure, using a quantitative (Abbott
      ARCHITECT) assay.
AB  - OBJECTIVES: Little is known about the effects of commonly used lubricants on
      detection of biomarkers of semen exposure. We investigated the in vitro effect of
      Gynol(r), K-Y Jelly(r), Replens(r), Astroglide(r), Carbopol, and Silicorel on
      quantitative detection of prostate specific antigen (PSA). STUDY DESIGN: A
      predetermined concentration of each of the gels was added to serially diluted
      semen samples. Additionally, serial dilutions of each of the gels were added to
      three different semen dilutions (high, medium, or low). The resulting samples
      were tested for PSA on the Abbott ARCHITECT System. RESULTS: When using the
      Abbott ARCHITECT system, the only products that inhibited PSA detection were
      Gynol(r) and Replens(r). The inhibition caused by Gynol(r) was dose-dependent,
      but that of Replens was dose-independent. K-Y Jelly(r)-spiked samples had higher
      PSA values than controls. CONCLUSIONS: Caution is warranted when using the Abbott
      quantitative assay for PSA detection as a biomarker of semen exposure in settings
      where Gynol(r), Replens(r) or K-Y Jelly(r) might also have been used. Neither
      Astroglide(r) nor Silicorel inhibited PSA detection. Additional studies
      evaluating other vaginal products, including microbicides, and their effects on
      other assays, are needed. In vivo studies will be especially important to
      optimize PSA detection from clinical samples. IMPLICATIONS: Researchers should
      consider the potential for specific lubricants or any vaginal products to affect
      the particular assay used for semen biomarker detection. The Abbott ARCHITECT's
      total PSA assay should not be used with the product Replens. Caution is warranted
      when using the assay in settings where Gynol or K-Y jelly may have been used.

PMID- 24314912
TI  - Trends in pharmacotherapy in patients referred to a bipolar specialty clinic,
      2000-2011.
AB  - OBJECTIVE: To assess mood stabilizer (MS) and second-generation antipsychotic
      (SGA) prescribing trends in bipolar disorder (BD) outpatients referred to a
      bipolar disorder specialty clinic over the past 12 years. METHOD: BD outpatients
      referred to the Stanford University Bipolar Disorder Clinic during 2000-2011 were
      assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD)
      Affective Disorders Evaluation. Prescription rates for MSs and SGAs were compared
      during the first (2000-2005) and second (2006-2011) six years. RESULTS: Among 597
      BD patients (mean+/-SD age 35.4+/-8.6 years; 58.1% female; 40.7% Type I, 43.6%
      Type II, and 15.7% Type Not Otherwise Specified; taking 2.6+/-1.7 prescription
      psychotropic medications), lamotrigine, quetiapine, and aripiprazole usage more
      than doubled, from 14.7% to 37.2% (p<0.0001), 7.2% to 19.7% (p<0.0001), and 3.1%
      to 10.9% (p=0.0003), respectively, while olanzapine and risperidone use decreased
      by more than half from 15.0% to 6.6% (p=0.0043), and from 8.7% to 3.8% (p=0.039),
      respectively. SGA use increased from 34.1% to 44.8% (p=0.013), although MS use
      continued to be more common (in 65.2% for 2006-2011). Use of other individual MSs
      and SGAs and MSs as a class did not change significantly. CONCLUSIONS: Over 12
      years, in patients referred to a BD specialty clinic, lamotrigine, quetiapine,
      and aripiprazole use more than doubled, and olanzapine and risperidone use
      decreased by more than half. Tolerability (for lamotrigine, aripiprazole,
      olanzapine, and risperidone) more than efficacy (for quetiapine) differences may
      have driven these findings. Additional studies are needed to explore the relative
      influences of enhanced tolerability versus efficacy upon prescribing practices in
      BD patients.

PMID- 24314913
TI  - Knowledge and provision practices regarding medical abortion among public
      providers in Hanoi, Khanh Hoa, and Ho Chi Minh City, Vietnam.
AB  - OBJECTIVE: To assess public service providers' knowledge of medical abortion (MA)
      and practices, and perspectives on expanding the use of MA to primary and
      secondary health facilities in Vietnam. METHODS: A cross-sectional study was
      conducted via an interviewer-administered questionnaire among abortion providers
      (n=905) from public health facilities between August 2011 and January 2012.
      RESULTS: Overall, 31.1% of providers performed both surgical and medical
      abortions; 68.9% offered only surgical abortion. Providers were knowledgeable
      about the regimen/dosage of mifepristone plus misoprostol regimen; however,
      knowledge scores were low for gestational age limits for MA, adverse effects of
      the combined drug regimen, and safety and effectiveness of MA compared with
      surgical abortion. Knowledge scores were significantly lower among providers in
      rural areas than among those in urban settings. A large proportion of providers
      (82.9%) thought that MA should be expanded to primary and secondary health
      facilities. Perceived barriers to MA expansion included lack of knowledge and
      training, qualified staff, adequate drug supplies, equipment, or facilities,
      guidelines and protocols on MA, and patient awareness. CONCLUSION: Provision of
      MA in Vietnam was found to be disproportionate to surgical abortion provision and
      to vary by region. Knowledge of MA was moderate, but poorer among providers in
      rural settings.

PMID- 24314914
TI  - Waveguide tapering for beam-width control in a waveguide transducer.
AB  - In a waveguide transducer that transmits an ultrasonic wave through a waveguide
      unit to a test structure, it is most preferred to send a non-dispersive
      ultrasonic wave of a narrow beam width. However, there is an unresolved conflict
      between the generation of the non- or less-dispersive wave and the transmission
      of a narrow-beam wave into a test structure. Among others, the thickness of the
      waveguide unit in a waveguide transducer is the key variable determining these
      two conflicting criteria, but the use of a uniformly-thick waveguide of any
      thickness cannot fulfill the two conflicting criteria simultaneously. In this
      study, we propose a specially-engineered tapered waveguide unit for the
      simultaneous satisfaction. An excitation unit is installed at the end of the thin
      region of the tapered waveguide and generates only the lowest non-dispersive
      shear-horizontal wave. Then the generated wave propagates through the tapered
      region of the waveguide unit and reaches the thick region of the waveguide with
      insignificant mode conversion to higher modes. If the tapered waveguide is used,
      the surviving lowest mode in the thick region of the waveguide is shown to carry
      most of the transmitted power and is finally propagated into a test structure.
      Because the beam size of the propagated wave and the thickness of the contacting
      waveguide region are inversely related, the thick contacting region of the
      tapered waveguide ensures narrow beam width. Numerical and experimental
      investigations were performed to check the effectiveness of the proposed
      waveguide-tapering approach. 

PMID- 24314915
TI  - Distal cervical caries in the mandibular second molar: an indication for the
      prophylactic removal of third molar teeth? Update.
AB  - In 2005 we reported the clinical findings of 100 patients who had mandibular
      third molars removed because of distal cervical caries in the mandibular second
      molar. The aim of this follow-up study was to find out whether the findings in a
      new group of patients corroborate those of our previous study. We report on the
      clinical features of 239 patients (mean (SD) age 32.1 (7.85) years, range 20-65)
      who had 288 mandibular third molars removed because of distal cervical caries in
      the second molar. Patients had better dental health than average, and 67% had a
      DMF (decayed, missing, or filled) score of 5 or less. In 89% of third molars the
      mesial angulation was between 40 degrees  and 80 degrees . Distal cervical caries
      in second molars is a late complication of third molar retention. The
      prophylactic removal of a partially erupted mesioangular third molar will prevent
      distal cervical caries forming in the second molar tooth. 

PMID- 24314916
TI  - Poorly circumscribed, long-standing tumor on the foot of an immigrant.
      Actinomycetoma of the foot.

PMID- 24314917
TI  - Ulcer on the scrotum.

PMID- 24314918
TI  - MicroRNA: key gene expression regulators.
AB  - MicroRNAs, also called miRNAs, are small 19-22 nucleotide (nt) sequences of
      noncoding RNA that work as endogenous epigenetic gene expression regulators. They
      are transcribed as large primary miRNAs or pre-miRNAs by RNA polymerase II and
      III, and are subsequently processed by the ribonucleases Drosha and Dicer to give
      rise to their mature forms. These mature miRNAs are then incorporated into the
      RISC complex (RNA-induced silencing complex) where they bind to the 3'-UTR mRNA
      complementary region, which induces their degradation or inhibits their
      translation, resulting in gene silencing. MicroRNAs are essential for embryo,
      cell, and tissue development, regulating cell differentiation, proliferation, and
      apoptosis, hence their importance in human reproduction. Currently, methods of
      detecting these molecules include real-time polymerase chain reaction,
      microarrays, in situ hybridization, and deep sequencing as well as novel
      approaches such as Nanostring nCounter. However, functional characterization is
      still required to confirm their biologic roles. Furthermore, miRNAs are not only
      found in cells but also have been identified in most biologic fluids, including
      serum, plasma, and saliva. Once miRNAs are secreted by cells, they are either
      incorporated into microvesicles or become associated with proteins, which protect
      them from RNase degradation so that they may remain intact for long periods of
      time. This suggests that they might also mediate paracrine signaling via
      different pathways and could therefore represent potential new biomarkers.
      Indeed, many pharmaceutic companies have recently started to investigate these
      molecules as possible routes to develop new human disease treatments. 

PMID- 24314919
TI  - Interleukin-6, interleukin-1beta, and tumor necrosis factor alpha in menstrual
      effluents as biomarkers of chronic endometritis.
AB  - OBJECTIVE: To assess the relationship between chronic endometritis (CE) and
      proinflammatory cytokine levels in menstrual effluents and to develop a simple
      noninvasive test for screening CE. DESIGN: Case-control study. SETTING: Academic
      center. PATIENT(S): Sixty-four women referred to our center for infertility.
      INTERVENTION(S): Office hysteroscopy; endometrial biopsy; collection of menstrual
      blood at subsequent cycle. MAIN OUTCOME MEASURE(S): Interleukin (IL) 6, IL-1beta,
      and tumor necrosis factor (TNF) alpha concentrations in menstrual effluents.
      RESULT(S): Thirty-six out of 64 infertile women had histologically proven CE. The
      remaining 28 women were included as controls. IL-6, IL-1beta, and TNF-alpha
      levels were markedly higher in menstrual effluents of women with CE compared with
      control subjects. Receiver operating characteristic curve analysis revealed a
      good CE screening capacity for all of the cytokines. The combined evaluation of
      either IL-6/TNF-alpha or IL-6/IL-1beta increased the diagnostic capacity of the
      test, which reached a 100% sensitivity and a negative predictive value of 100
      when at least one cytokine was found to exceed its cutoff value; it also reached
      a 100% specificity and a positive predictive value of 100 in cases of positivity
      of both cytokines. Logistic regression analysis confirmed the IL-6/TNF-alpha
      based model as a significant predictor of CE. CONCLUSION(S): Proinflammatory
      cytokine levels are increased in menstrual effluents of women with CE. A test
      dosing IL-6 and TNF-alpha seems to have a high screening capacity for CE.

PMID- 24314920
TI  - Misconduct in third-party assisted reproduction: a committee opinion.
AB  - Physicians who are told or discover information that would be material to another
      party's participation in an assisted reproductive technology (ART) arrangement
      (such as lawyer's, donor's, gestational carrier's, or intended parent's) should
      encourage disclosure to that party. In some instances, it is ethically and
      legally permissive for the physician to either disclose material information to
      an affected party or to transfer care of a patient to another willing provider.
      In all cases involving the legal status or rights of the parties, referral to
      legal professionals is advised. 

PMID- 24314921
TI  - Beneficial effect of resveratrol on bovine oocyte maturation and subsequent
      embryonic development after in vitro fertilization.
AB  - OBJECTIVE: To analyze the potential beneficial effects and mechanisms of action
      of resveratrol on the maturation of bovine oocytes that were incubated in
      different concentrations of resveratrol (0.1, 1.0, or 10.0 MUM) as germinal
      vesicle-stage oocytes. DESIGN: In vitro prospective study. SETTING: University
      research laboratory. ANIMAL(S): Animal models for human studies. INTERVENTION(S):
      In vitro culture in the presence of various concentrations of the antioxidant
      resveratrol. MAIN OUTCOME MEASURE(S): Parameters of hormone levels, oocyte
      nuclear maturation, cumulus expansion, levels of intracellular glutathione and
      reactive oxygen species, embryonic cleavage, blastocyst formation, gene
      expression associated with mature bovine oocytes and cumulus cells, and level of
      sirtuin 1 gene expression. RESULT(S): Resveratrol statistically significantly
      increased progesterone secretion and decreased estradiol-17beta secretion by
      cumulus cells. The elevated levels of progesterone activated the Mos/MEK/p42
      mitogen-activated protein kinase (MAPK) cascade in the oocytes. At a
      concentration of 1.0 MUM, resveratrol statistically significantly improved
      cumulus expansion, polar body formation, the (hatched) blastocyst rate, and the
      mean number of cells/blastocysts. Meanwhile, resveratrol statistically
      significantly reduced the level of reactive oxygen species (ROS) and increased
      the level of glutathione (GSH). For the first time, the expression of the sirtuin
      1 gene was identified in granulosa cells, cumulus cells, oocytes, and
      blastocysts. Further studies revealed that resveratrol promoted sirtuin-1 gene
      expression. CONCLUSION(S): Resveratrol promoted bovine oocyte maturation and
      subsequent post-in vitro fertilization embryonic development by inducing
      progesterone secretion and an antioxidant effect, probably in a manner dependent
      on sirtuin-1.

PMID- 24314922
TI  - Cytomegalovirus and human immunodeficiency virus in semen of homosexual men.
AB  - OBJECTIVE: To assess the accuracy of serology to predict the presence of
      cytomegalovirus (CMV) in semen of homosexual men without and with HIV
      coinfection. DESIGN: Semen CMV was detected by electron microscopy and by
      polymerase chain reaction (PCR) amplification; paired serum was tested for CMV
      IgG/IgM. Semen HIV was detected by reverse transcription-PCR. SETTING: Licensed
      clinical and research laboratory. PATIENT(S): Sixty-eight men. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Frequency of CMV and HIV in semen. RESULT(S):
      Cytomegalovirus was detected by electron microscopy in 3 of 10 specimens
      examined. Forty-six (89%) of 52 HIV-infected men were seropositive for CMV by
      combined assay for IgG/IgM; two more (48 of 52, 92%) were seropositive for CMV
      IgG by separate assay; 25 (48%) of the HIV-infected men had PCR-detectable CMV
      DNA in at least one semen specimen, 22 of whom (42%) had CMV in all specimens.
      Nineteen (13%) of the 150 specimens tested positive for HIV, whereas 67 (45%)
      tested positive for CMV; seven specimens tested positive for both CMV and HIV.
      Cytomegalovirus, but not HIV, detection in semen correlated with decreased CD4(+)
      lymphocytes in peripheral blood (<700/MUL) but was not accurately predicted by
      serology, leukocytospermia, or age. CONCLUSION(S): Cytomegalovirus in semen is
      not accurately predicted by serology. Sperm banking needs to include direct
      assessment of CMV in semen specimens. Strategies to eliminate CMV from semen
      specimens are needed to alleviate the risk of virus transmission.

PMID- 24314924
TI  - Informed consent and the use of gametes and embryos for research: a committee
      opinion.
AB  - The ethical conduct of human gamete and embryo research depends upon
      conscientious application of principles of informed consent developed in the
      context of clinical research. This document explores these principles, which
      entail, for example, that investigations occur under Institutional Review Board
      oversight. This document also discusses the complexities in obtaining informed
      consent from the persons whose gametes or embryos are being used in research but
      were originally intended for reproductive purposes. This statement replaces the
      document of the same name last published in 2004 (Fertil Steril 2004;82:S251
      252). 

PMID- 24314925
TI  - Does the S phase have an impact on the accuracy of comparative genomic
      hybridization profiles in single fibroblasts and human blastomeres?
AB  - OBJECTIVE: To investigate if there is an association between single-cell
      replicative stage and the segmental chromosome imbalances detected by comparative
      genomic hybridization (CGH). DESIGN: First, 135 fibroblasts from cell-line
      GM03184 (Coriell) at three cell stages (G0/G1, S, and G2/M) were amplified by
      degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) or Sureplex
      and blindly analyzed by CGH. Second, 85 human blastomeres at the interphase and
      the metaphase stages, from 30 donated human cryopreserved embryos, were amplified
      by Sureplex and analyzed by CGH. SETTING: Academic center for reproductive
      medicine. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Incidence of aneuploidy and segmental imbalances detected at the different cell
      stages. RESULT(S): In DOP-PCR amplifications of fibroblasts, an increased
      incidence of segmental abnormalities was detected in the S phase. In Sureplex
      amplifications of fibroblasts and blastomeres, no differences were detected
      between the different cell stages. A significantly increased incidence of
      structural abnormalities was seen in the aneuploid blastomeres. CONCLUSION(S):
      The segmental imbalances detected after Sureplex amplification in 73.3% of the
      cryopreserved embryos analyzed are mainly nontransitory. They correspond to
      segmental imbalances present in the cells due to chromosome instability, rather
      than to replicative DNA segments.

PMID- 24314923
TI  - Germline stem cells: toward the regeneration of spermatogenesis.
AB  - Improved therapies for cancer and other conditions have resulted in a growing
      population of long-term survivors. Infertility is an unfortunate side effect of
      some cancer therapies that impacts the quality of life of survivors who are in
      their reproductive or prereproductive years. Some of these patients have the
      opportunity to preserve their fertility using standard technologies that include
      sperm, egg, or embryo banking, followed by IVF and/or ET. However, these options
      are not available to all patients, especially the prepubertal patients who are
      not yet producing mature gametes. For these patients, there are several stem cell
      technologies in the research pipeline that may give rise to new fertility options
      and allow infertile patients to have their own biological children. We will
      review the role of stem cells in normal spermatogenesis as well as experimental
      stem cell-based techniques that may have potential to generate or regenerate
      spermatogenesis and sperm. We will present these technologies in the context of
      the fertility preservation paradigm, but we anticipate that they will have broad
      implications for the assisted reproduction field. 

PMID- 24314926
TI  - Treatment-resistant depression: definitions, review of the evidence, and
      algorithmic approach.
AB  - BACKGROUND: Most adults with major depressive disorder (MDD) fail to achieve
      remission with index pharmacological treatment. Moreover, at least half will not
      achieve and sustain remission following multiple pharmacological approaches.
      Herein, we succinctly review treatment modalities proven effective in treatment
      resistant depression (TRD). METHODS: We conducted a review of computerized
      databases (PubMed, Google Scholar) from 1980 to April 2013. Articles selected for
      review were based on author consensus, adequacy of sample size, the use of a
      standardized experimental procedure, validated assessment measures and overall
      manuscript quality. RESULTS: The evidence base supporting augmentation of
      conventional antidepressants with atypical antipsychotics (i.e., aripiprazole,
      quetiapine, and olanzapine) is the most extensive and rigorous of all
      pharmacological approaches in TRD. Emerging evidence supports the use of some
      psychostimulants (i.e., lisdexamfetamine) as well as aerobic exercise. In
      addition, treatments informed by pathogenetic disease models provide preliminary
      evidence for the efficacy of immune-inflammatory based therapies and metabolic
      interventions. Manual based psychotherapies remain a treatment option, with the
      most compelling evidence for cognitive behavioral therapy. Disparate
      neurostimulation strategies are also available for individuals insufficiently
      responsive to pharmacotherapy and/or psychosocial interventions. LIMITATIONS:
      Compared to non-treatment-resistant depression, TRD has been less studied. Most
      clinical studies on TRD have focused on pharmacotherapy-resistant depression,
      with relatively fewer studies evaluating "next choice" treatments in individuals
      who do not initially respond to psychosocial and/or neurostimulatory treatments.
      CONCLUSION: The pathoetiological heterogeneity of MDD/TRD invites the need for
      mechanistically dissimilar, and empirically validated, treatment approaches for
      TRD.

PMID- 24314927
TI  - In situ EBSD during tensile test of aluminum AA3003 sheet.
AB  - Miniature tensile-test specimens of soft-annealed, weakly textured AA3003
      aluminum sheet in 0.9 mm thickness were deformed until fracture inside a scanning
      electron microscope. Tensile strength measured by the miniature tensile test
      stage agreed well with the tensile strength by regular tensile testing. Strain
      over the microscope field of view was determined from changes in positions of
      constituent particles. Slip lines were visible in secondary electron images
      already at 0.3% strain; activity from secondary slip systems became apparent at
      2% strain. Orientation rotation behavior of the tensile load axis with respect to
      the crystallographic axes agreed well with previously reported trends for other
      aluminum alloys. Start of the fracture and tensile crack propagation were
      documented in secondary electron images. The region of fracture nucleation
      included and was surrounded by many grains that possessed high Schmid factors at
      zero strain. Crystal lattice rotation angles in the grains surrounding the
      initial fracture zone were higher than average while rotations inside the initial
      fracture zone were lower than average for strains from zero to 31%. The
      orientation rotation behavior of the tensile load axes of the grains around the
      fracture zone deviated from the average behavior in this material.

PMID- 24314928
TI  - The Middle East Society for Organ Transplantation (MESOT). Preface.

PMID- 24314929
TI  - The future of replacement and restorative therapies: from organ transplantation
      to regenerative medicine.
AB  - As we continue to have severe shortages of organs for transplantation, we need to
      consider alternatives for the future. The most likely to make a real difference
      in the long term is regenerative medicine (RM), a field that has emerged from the
      conjunction of stem cell biology and cell therapies; gene therapy; biomaterials
      and tissue engineering; and organ transplantation. Transplantation and RM share
      the same essential goal: to replace or restore organ function. Herein I briefly
      review some major breakthroughs of RM that are relevant to the future of organ
      transplantation, with a focus on the needs of people in the developing world. A
      definition of RM is provided and the ethical, legal, and social issues are
      briefly highlighted. In conclusion, I provide a projection of what the future may
      be for RM.

PMID- 24314930
TI  - Prograf five milligrams versus Tacrolimus medis in healthy volunteers: a
      bioequivalence study.
AB  - For FDA approval, bioequivalence of a generic version of Tacrolimus must be
      demonstrated in a randomized, two-treatments, two-periods, two-sequences, single
      dose crossover study in healthy adult volunteers. Currently there are at least 3
      differents generic equivalent for Tacrolimus, that are approved by the EMA and
      the FDA, with a USA market share of nearly 50%. However, the market share of
      generic immunosuppressive drugs in the Middle East region is still very low due
      to the reluctance of the physician to accept Tacrolimus generics, considered to
      be a narrow therapeutic window drug, that are approved using the standard
      bioequivalence criteria of 80% to 125%. Herein we present a bioequivalence study
      of a new Tacrolimus generic, Tacrolimus Medis 5 mg developed by Medis Tunisia
      batch number 12G3003 compared with Prograf(r) 5 mg batch number 7202 manufactured
      by Astellas Toyama Co., Ltd. Japan and HIKMA Pharmaceuticals, Amman-Jordan in
      healthy adult volunteers using the 90%-111% criteria recommended for drugs with
      narrow therapeutic window. The study was, balanced, randomized, two-treatments,
      two-periods, two-sequences, single dose, crossover, comparative oral
      bioavailability study in healthy adult human volunteers. The study was carried
      out in accordance with the Basic Principles defined in the U.S. 21 CFR Part
      312.20, the principles enunciated in the Declaration of Helsinki (World Medical
      Association Declaration of Helsinki). Thirty six non-smoking healthy, as
      determined by medical history, volunteers, 18 years and older, were included.
      Following randomization using a computer software (pharma solution) the
      volunteers were given a single oral dose of 5 milligrams following a 12 hour fast
      with a wash out period of 7 days. Pharmacokinetics profile with blood levels at:
      0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours were performed following
      each dose. Tacrolimus plasma level was determined using an HPLC validated method
      (Transmedical For Life S.A.R.L. Beirut Lebanon), for accuracy, suitability,
      reproducibility, precision , long-term stability and robustness. Physical
      examinations, hematology, urine analysis and serum chemistry tests were performed
      at screening and before dosing in each period and at end of the study. Volunteers
      were monitored for safety and adverse events throughout the study. Both products
      were bioequivalent at the entire pharmacokinetic parameters tested. The LSM were
      95.31%-101.21% for AUC, 94.65%-101.11% for AUC0-inf, 97.15%-100.02% for Cmax and
      91.54%-103.75% for Half-life. Respectively all of which are within the EU and FDA
      approval limits (90-111%) indicating that the 2 products are equivalent and
      switchable. 

PMID- 24314931
TI  - Evaluation of pulmonary infections in solid organ transplant patients: 12 years
      of experience.
AB  - BACKGROUND: Recipients of solid organ transplants (SOTs) are at higher risk to
      develop pulmonary infections (PIs) owing to their immunocompromised state.
      Flexible bronchoscopy (FB) is frequently performed to diagnose nature of these
      infections. The aim of 12-year review was to evaluate the demographic
      characteristics of SOT recipients with PIs and to study diagnostic utility of FB
      in this group of patients. METHODS: Medical records of patients who underwent SOT
      as well as FB between 2000 and 2012 were retrospectively reviewed. Patients'
      demographics, type of transplantation, primary diagnoses, thoracic computed
      tomography (CT) findings, total blood count and chemistry, indication for FB, FB
      results, specimen culture results, and suspected and final diagnoses were all
      recorded. If the bronchoscopy findings altered medical management and produced
      improvement in PI, the procedure was considered diagnostic. RESULTS: Ninety of
      998 liver, heart, or kidney transplant recipients underwent FB (73 renal, 16
      liver, and 1 heart; mean age, 42.3 +/- 12.1 years) during the study period. CT
      findings were as follows: Consolidation (49.4%), lymphadenopathy (3.4%), nodular
      infiltrates (5.6%), and cavitary lesion (1.1%). FB was unremarkable in 29, but
      showed increased secretions in 33 patients (36.7%), chronic mucosal changes in 9
      (10%), edema in 7 (7.8%), mucosal plaque in 7 (7.8%), friable mucosa in 3 (3.3%),
      and endobronchial lesion in 2 (2.2%). A total of 29 bronchial washings (BW;
      32.6%) and 10 bronchoalveolar lavages (BAL; 11.2%) were performed. PI was
      diagnosed in 82% of the patients (n = 73). In 32 patients (36%), micro-organism
      growth was observed on either BW or BAL. Mycobacterium tuberculosis was detected
      in 6 (6.7%), Staphylococcus aureus in 4 (4.4%), Moraxella catharralis in 4
      (4.4%), Candida albicans in 6 (6.7%), Klebsiella pneumonia in 2 (2.2%),
      Escherichia coli in 2 (2.2%), Streptococcus pneumoni in 2 (2.2%), Stenotrofomonas
      maltofilia in 1 (1.1%), Aspergillus fumigatus in 4 (4.5%), and Pseudomonas
      aeruginosa in 1 (1.1%). Final diagnosis was established by FB (n = 33) with a
      diagnostic yield of 36%. No significant finding was observed between the type of
      the transplant and the culture results (P > .05). CONCLUSION: Suspected PI is the
      most common indication for FB in SOT recipients. It may identify the causative
      organism in >30% of patients. Tuberculosis was found to be the most frequent
      agent, which is not surprising from such an endemic area. Bacteria were more
      common than fungal or viral micro-organisms. FB should be considered in SOT
      recipients presenting with lung infiltrates and suspected to have PI.

PMID- 24314932
TI  - Organ Donation European Quality System: ODEQUS project methodology.
AB  - Differences in the number of organ donors among hospitals cannot be explained
      only by the number of intensive care unit beds used or neurologic patients
      treated. The figures obtained are influenced by the organizational structure of
      the donation process and how efficient it is. The Organ Donation European Quality
      System (ODEQUS) is a 3-year project (from October 2010 to September 2013) co
      financed by the European Agency for Health and Consumers (EAHC20091108) which
      aims to define a methodology to evaluate organ procurement performance at the
      hospital level. ODEQUS's specific objectives are to identify quality criteria and
      to develop quality indicators in three types of organ donation (after brain
      death, after cardiac death, and living donation). Those tools will be useful for
      hospitals' self-assessment as well as for developing an international auditing
      model. A consortium has been established involving 14 associated partners from
      Austria, Croatia, France, Germany, Italy, Poland, Portugal, Romania, Spain,
      Sweden, and the United Kingdom, as well as five collaborating partners from
      Greece, Hungary, Malta, Slovenia, and Turkey. The project has been established in
      three steps: 1) Design of a survey about the use of quality tools in a wide
      sample of European hospitals; 2) Development of quality criteria and quality
      indicators by the project experts. The main fields considered have been
      organizational structures, clinical procedures, and outcomes; and 3) Elaboration
      of an evaluation system to test the quality indicators in 11 European hospitals.
      Two types of training have been designed and performed: one concerns the
      development of quality criteria and quality indicators, whereas another is
      focused on how to use evaluation tools. Following this methodology, the project
      has so far identified 131 quality criteria and developed 31 quality indicators.
      Currently, the quality indicators are being tested in 11 selected hospitals.

PMID- 24314933
TI  - University hospital doctors: what are their beliefs about organ donation?
AB  - INTRODUCTION: Organ and human tissue donation is not well developed in Morocco.
      This is due in part to the refusal of families, but also to a lack of awareness.
      We conducted a survey of a representative sample of doctors more exposed to the
      donation process to assess their knowledge and attitudes toward organ donation
      and their training needs. METHODS: This is a cross-sectional study of physicians
      in Marrakech University Hospital. An anonymous questionnaire adapted to Moroccan
      context, assessing the knowledge, opinions, attitudes, and needs regarding organ
      donation was given to doctors. RESULTS: Among 130 distributed questionnaires, we
      collected 115 completely answered surveys. Respondees were as follows: 60.8% were
      females, 87 were residents and 28 interns, 80% were aged from 25 to 34 years, and
      60% had practiced their profession for 1 to 5 years. Results showed that 28%
      don't know that tissue and organ donation from a cadaver is authorized in
      Morocco, 6% are aware of the organs and tissues that can be taken, 76% know the
      definition of brain death, 35% don't believe in this concept, 88% were favorable
      for the removal of organs and tissue of deceased persons, 10% ignore that Islam
      allows organ donation, 62% will give their organs and tissues after death, 25%
      refuse organ donation of a parent, and 30% refuse it of their children after
      death. CONCLUSIONS: Our findings show that there is discordance between knowledge
      and attitudes of doctors in our hospital toward organ donation. The promotion of
      organ donation requires good training of our teams to sensitize the population.

PMID- 24314934
TI  - Public awareness survey about organ donation and transplantation.
AB  - BACKGROUND: This survey was conducted to assess the public perception on organ
      donation and transplantation. METHODS: A random sample of the population
      attending the outpatient clinics in Dhahran Military Hospital, Saudi Arabia, from
      December 1, 2011, to January 31, 2012, answered a questionnaire related to the
      above aim. RESULTS: From 582 subjects who answered the questionnaire, 85 were
      excluded for incoherent answers. From the remaining 497, 77.7% were males and
      22.3% females with the age ranging from 18 to 65 years, and the majority was at a
      secondary or university level of education. More than 90% were aware organ
      transplantation and donation. From a religious point of view, 68.6% considered it
      legal to donate organs versus 26.2%. Those who disagreed with the concept of
      donation believed that one kidney is not enough to survive (50%), and that the
      remaining kidney may be affected (25.8%), whereas 15.2% expressed fear of the
      operation. Kidney transplantation was the preferred treatment for 73.2% of
      respondents and 12.75% were in favor of dialysis. Regarding financial incentive,
      14.5% asked for reward from the government, 3.4% believed that the reward should
      come from the donor, and the majority (82.1%) stated that organ donation should
      be for the sake of God. Finally, there was a 61.2% willingness of respondents to
      donate relatives' organs after brain death. CONCLUSION: The level of awareness
      about donation and transplantation in our population was found to be
      satisfactory. Religion was not a bar for organ donation; moreover, financial
      incentive was not found to be a positive stimulus toward donation because the
      majority was willing to donate for the sake of God.

PMID- 24314935
TI  - Toll-like receptor 4 and CD14 gene polymorphisms in Tunisian kidney
      transplantation.
AB  - BACKGROUND: Acute and chronic rejections remain an important cause of graft loss
      after renal transplantation. Currently, activation of innate immune responses
      through Toll-like receptors (TLRs) is suspected to be implied in the loss of the
      transplant tolerance. OBJECTIVES: We investigated functional single nucleotide
      polymorphisms (SNPs) of TLR4 and its coreceptor CD14 in kidney transplantation
      and looked for any potential role in acute rejection (AR) and chronic allograft
      nephropathy (CAN) and impact on graft survival. PATIENTS AND METHODS: TLR4
      (Asp299Gly) and CD14 (C/T -159) SNPs were detected using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) in 209 kidney
      transplant recipients (KTRs) including 132 treated with mycophenolate mofetil
      (MMF+). AR occurred in 59 patients and 24 were identified as having CAN by biopsy
      and scored according to the Banff criteria. RESULTS: There were no significant
      associations between TLR4 and CD14 genotypes and alleles and the occurrence of
      both AR episodes and CAN. Moreover, TLR4 and CD14 SNPs did not seem to influence
      kidney graft survival. Analysis according to human leukocyte antigen (HLA)
      compatibility status, positivity of anti-HLA antibodies, and immunosuppression by
      MMF confirmed the absence of correlation of the investigated SNPs with the graft
      outcome. In addition, incidence of post-transplantation infections, including
      cytomegalovirus (CMV) infections, was not influenced by both TLR4 and CD14 SNPs.
      CONCLUSION: These results suggest that TLR4 (Asp299Gly) and CD14 (C/T -159)
      functional SNPs do not play a major role in AR, CAN, and kidney graft survival.
      Therefore, intragraft monitoring of TLR4/CD14 genes expression by messenger RNA
      (mRNA) would provide clarity on the exact role of these receptors in graft
      injuries.

PMID- 24314936
TI  - The prevalence and types of cardiovascular disease in patients with end-stage
      renal disease undergoing renal transplantation.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the most common cause of death in
      patients with end-stage renal disease (ESRD) as well as in renal transplant
      recipients (RTR). In this study we sought to evaluate the prevalence and the
      types of CVD in patients with ESRD undergoing renal transplantation. PATIENTS AND
      METHODS: The data of 500 consecutive patients with ESRD undergoing renal
      transplantation were evaluated retrospectively. Demographic findings, clinical
      variables, and laboratory results including invasive and noninvasive cardiologic
      tests were recorded. RESULTS: The mean age of patients was 31.6 +/- 10.2 years,
      of whom 133 (26.6%) were female. The prevalence of major atherosclerotic risk was
      as follows: hypertension 62.2%, diabetes mellitus 3.4%, smoking 26.4%,
      dyslipidemia 13.2%, and family history of atherosclerosis 9.8%. Treadmill
      exercise test was performed on 139 subjects, and myocardial perfusion
      scintigraphy on 73. Coronary artery disease was identified in 16 of 42 cases
      (38.1%) who had undergone angiography. Eight patients underwent percutaneous
      coronary intervention, and coronary bypass surgery was performed on 4 cases prior
      to renal transplantation. On echocardiographic examination mean ejection fraction
      was 51.9 +/- 7.1%, and wall motion abnormality was detected in 15% of cases. The
      most prevalent valvular disease was mitral regurgitation (45.8%) followed by
      tricuspid regurgitation (30.6%). CONCLUSION: The findings of this study indicate
      that CVD and atherosclerotic risk factors are common in patients with ESRD
      undergoing renal transplantion. With regard to the prognostic significance,
      pretransplantation identification of these conditions is of paramount importance.
      As a result, improved detection of occult CV disorders results in the possiblity
      of improved outcomes following renal transplantation.

PMID- 24314937
TI  - Dialysis patients with the metabolic syndrome need less recombinant human
      erythropoietin for similar hemoglobin levels.
AB  - INTRODUCTION: The metabolic syndrome (MS) components, such as dyslipidemia,
      prothrombotic status, and increased blood pressure, are risk factors for patients
      with renal disease. Visceral fat mass is closely related to the MS and
      atherosclerosis. We investigated the effects of body compositions and MS on
      anemia parameters and recombinant human erythropoietin (rHuEPO) requirements in
      maintenance hemodialysis patients. METHODS: Body composition (body mass index and
      bioimpedance analysis) and laboratory data were obtained from 110 dialysis
      patients. The MS was identified according to ATP-III criteria. Anemia parameters,
      hemoglobin (Hgb), albumin, C-reactive protein (CRP), calcium, phosphorus,
      parathormone levels, and rHuEPO requirements over the last 6 months were
      retrospectively analyzed. RESULTS: Patients with the MS seem to reach target Hgb
      levels more frequently (10-12 g/dL; 66.3% vs 84.8%; P = .03) without any
      difference in total intravenous iron therapy dosage. MS patients also required
      lower rHuEPO for reaching similar Hgb levels compared with patients without MS
      (2679.3 +/- 1936.1 vs 3702.5 +/- 2213.0 U/kg/6 mo; P = .02). There were no
      differences in serum CRP, albumin, or Hgb levels between the 2 groups (P > .05).
      We observed that patients with MS had significantly higher fat mass and visceral
      fat ratio, but similar muscle mass values compared with no-MS counterparts (P =
      .0001 and .001, respectively). However, when we compared the ratios of these
      parameters we observed a significant reduction in muscle ratios and a significant
      increase in fat ratios of MS patients (P = .0001). CONCLUSION: Our results
      indicate that MS might be an advantage for reaching higher Hgb levels with lower
      rHuEPO dosages. The possible reason for this might be the good nutritional state
      and increased fat mass of patients with MS.

PMID- 24314938
TI  - Reliability of bioelectrical impedance analysis in the evaluation of the
      nutritional status of hemodialysis patients - a comparison with Mini Nutritional
      Assessment.
AB  - INTRODUCTION: Protein-energy wasting (PEW) is a strong predictive factor for
      morbidity and mortality in patients who have end-stage renal disease (ESRD). Mini
      Nutritional Assessment (MNA) is an important and confirmed tool to evaluate PEW
      that has been recommended by many guidelines. Bioelectrical impedance analysis
      (BIA) is a noninvasive technique for assessing body composition. The aim of the
      present study was to analyze the reliability of BIA in malnutrition diagnosis by
      comparing it with standard MNA in a group of 100 ESRD patients. METHODS: One
      hundred ESRD patients who were medically stable and under dialysis treatment for
      at least 6 months were enrolled to the study. Monthly assessed serum creatinine,
      albumin, C-reactive protein (CRP), and lipid profiles from the last 6 months
      prior to the study were retrospectively collected. A standard Full-MNA and body
      composition analyses were applied to all patients. Body compositions were
      analyzed with the BIA technique using the Body Composition Analyzer (Tanita BC
      420 MA; Tanita, Tokyo, Japan). Patients were classified into three groups
      according to MNA scores as PEW (n = 15, score <17), moderate PEW or risk group (n
      = 49, score 17-23.5), and well-nourished (n = 36, score >= 24) patients. RESULTS:
      Mean duration of maintenance hemodialysis treatment was significantly shorter in
      the PEW group compared to both of the other groups described (P = .015). Well
      nourished and risk groups had lower CRP and higher albumin levels compared to PEW
      patients; however, these values were statistically similar in these two groups (P
      = .018, .01, respectively). According to BIA findings, well-nourished patients
      had the highest fat ratio, fat mass, muscle mass, visceral fat mass, and fat-free
      mass compared to both moderate the PEW/risk and the PEW groups (P < .05). Risk
      group patients also had higher muscle mass, visceral fat mass, and fat-free mass
      values compared to the PEW group (P < .05). A correlation analysis revealed that
      MNA scores were positively correlated with albumin (P = .005), creatinine (P =
      .049), fat mass (P = .045), muscle mass (P = .001), visceral fat ratio (P =
      .007), and BMI (P = .047) and in negative correlation with CRP (r = -0.357, P =
      .0001) levels. CONCLUSIONS: We recommend BIA as a complementary diagnostic tool
      to evaluate nutritional status of ESRD along with MNA, anthropometric measures,
      and classical biochemical markers.

PMID- 24314939
TI  - Body composition analysis of patients on waiting list for cadaveric renal
      transplantation: a comparison of hemodialysis and peritoneal dialysis patients.
AB  - BACKGROUND: Bioelectrical impedance analysis is a simple, noninvasive method of
      assessing body composition. Dialysis modality and selection of buffer type may
      have an impact on body composition. The aim of our study was to compare body
      compositions of patients from the waiting list for cadaveric renal
      transplantation according to the dialysis modality. METHODS: We examined a total
      of 152 (110 hemodialysis [HD] and 42 continuous ambulatory peritoneal dialysis
      [CAPD]) patients. Demographic data were collected from patient charts. The last 6
      months routine laboratory evaluations including hemoglobin, serum creatinine,
      intact parathyroid hormone, albumin, C reactive protein, calcium, phosphorus were
      collected. Body compositions were measured using the Tanita BC-420MA Body
      Composition Analyzer (Tanita, Tokyo, Japan). We made a subanalysis of the CAPD
      group according to buffer choices as follows: lactate-buffered (n = 16) and
      bicarbonate/lactate-buffered (n = 26) solution users. RESULTS: The body weight (P
      = .022), body mass index (BMI; 25.8 +/- 4.7 vs 23.4 +/- 4.9 kg/m(2), P = .009),
      muscle mass (P = .01), fat-free mass (P = .013), and visceral fat ratio (9.5 +/-
      5.4 vs 7.3 +/- 4.1 %, P = .022) were significantly higher in the CAPD group.
      Total body water of CAPD patients were also higher (P = .003), but total body
      water ratios of HD and CAPD groups were similar. Fat and fat-free mass ratios of
      patient groups were also similar. Comparing CAPD subgroups we observed that
      patients using bicarbonate/lactate-buffered solutions had higher body weights (P
      = .038), BMI (27.1 +/- 5 vs 23.7 +/- 3.5 kg/m(2), P = .018) values, and visceral
      fat ratios (8.0 +/- 5.2 vs 4.6 +/- 2.5 %, P = .023). These patients also tend to
      have higher fat mass without statistical significance (P = .074). Fat, muscle,
      and fat-free mass total body water ratios of peritoneal dialysis subgroups were
      similar. CONCLUSION: We believe that body composition analysis should be used as
      a complementary method for assessing nutritional status of PD and CAPD patients
      as body weight or BMI measurements do not reflect fat, muscle masses, and
      visceral fat ratios in these patients. Stable, well nourished CAPD patients
      should be closely observed and be encouraged to increase daily exercise and/or
      decrease calorie intake from other sources to decrease risks associated with
      abdominal obesity.

PMID- 24314940
TI  - Male sexual function in patients receiving different types of renal replacement
      therapy.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) experience erectile
      dysfunction (ED). Although it is a benign disorder, ED is related to physical and
      psychosocial health, and it has a significant impact on the quality of life
      (QOL). The objective of the present study was to investigate the effects of
      different renal replacement therapies on ED. METHODS: A total of 100 ESRD
      patients and 50 healthy men were recruited to the present cross-sectional study.
      The study was consisted of 53 renal transplantation (RT; group I; mean age, 39.01
      +/- 7.68 years; mean duration of follow-up, 97.72 +/- 10.35 months) and 47
      hemodialysis (HD) patients (group II; mean age, 38.72 +/- 9.12 years; mean
      duration of follow-up, 89.13 +/- 8.65 months). The control group consisted of 50
      healthy men (group III; mean age 39.77 +/- 8.51 years). Demographic data and
      laboratory values were obtained. All groups were evaluated with the following
      scales: International Index of Erectile Function (IIEF)-5 and Short Form (SF)-36
      questionnaires, and Beck Depression Inventory (BDI). The patients whose IIEF
      score were <= 21 were accepted as having ED. RESULTS: The mean age of these
      groups were similar (P > .05). Total IIEF-5 scores of men in groups I, II, and
      III were 19.5 +/- 4.5, 16.4 +/- 5.9, and 22.5 +/- 3.4, respectively. The mean
      total IIEF-5 score of control group was higher than those of groups I and II (P <
      .001). Posttransplant group mean total IIEF-5 score was also higher than the HD
      group (P < .05). Groups I and II significantly differed from control group in
      terms of presence of ED (IIEF score <= 21: Group I, n = 28 [52.8%]; group II, n =
      29 [61.7%]; and group III, n = 12 [%24], respectively [P < .001]), whereas there
      was no difference between groups I and II. In the logistic regression analysis
      (variables included age, BDI, and renal replacement therapy [HD and
      transplantation]), ED was independently associated with age (odds ratio [OR],
      1.1; 95% confidence interval [CI], 1.05-1.2), BDI (OR, 1.1; 95% CI, 1.01-1.13).
      Additionally, ED was not associated with renal replacement therapy (OR, 1.46; 95%
      CI, 0.60-3.57). Physiologic health domain of SF-36 was significantly better in
      healthy controls (P < .001). Patient groups were similar in terms of BDI score (P
      > .05). ED score was negatively correlated with BDI (r = -0.368; P < .001), and
      positively correlated with SF-36 (r = 0.495; P < .001) in all patient groups.
      CONCLUSION: Patients with ESRD had significantly lower sexual function and lower
      QOL scores than the healthy control men. Notably, the mode of renal replacement
      therapy had no impact on male sexual function.

PMID- 24314941
TI  - African American renal transplant recipients (RTR) require higher tacrolimus
      doses to achieve target levels compared to white RTR: does clotrimazole help?
AB  - The number of African Americans (AAs) on the kidney waiting list is increasing in
      the United States. Several studies showed that AAs are at higher risk for
      rejection and graft loss. Because of genetic polymorphisms, AAs may metabolize
      calcineurin inhibitors faster than Caucasian (C) individuals. The goal of this
      study is to evaluate the tacrolimus (TAC) dose required to reach therapeutic
      levels and to assess the impact of clotrimazole on TAC metabolism in AAs compared
      to C patients. One hundred forty-two AA renal transplant recipients (RTRs) were
      compared to 309 C RTRs. Demographics were similar in both groups. Induction
      therapy and maintenance immunosuppression were similar in both groups and
      included TAC, mycophenolate acid (MPA), and steroids. The goal in all RTRs was to
      maintain a 12-hour trough level of 10 to 15 ng/mL in the first 3 months, 8 to 10
      ng/mL for the first year, and 5 to 8 ng/mL thereafter. To achieve these levels,
      AA RTRs require a significantly higher dosage of TAC compared to C patients (5.9
      +/- 2.9 vs 3.6 +/- 2 mg/d, respectively, P < .0001). By multivariate analysis,
      TAC dose requirements were not affected by age, gender, MPA or prednisone dose,
      diabetes, and renal function. Adding clotrimazole (CTM) to the RTR regimen
      significantly reduced the TAC dose requirements in all RTRs. When CTM was used,
      the TAC dose requirement was not statistically significantly different between AA
      and C patients (2.6 +/- 1.2 mg/d vs 1.8 +/- 1.5 mg/d, P = .07). We conclude that
      AAs required a higher TAC dose to reach the desired trough level in RTRs compared
      to C RTRs. The use of CTM eliminates the need for higher doses of TAC in AA RTRs.
      Thus, CTM may aid AA RTRs in achieving therapeutic TAC levels while reducing drug
      costs.

PMID- 24314942
TI  - Long-term outcome of renal transplantation in patients with familial
      Mediterranean fever amyloidosis: a single-center experience.
AB  - INTRODUCTION: Familial Mediterranean fever (FMF) is an autosomal-recessive
      disorder, affecting multiple organs. The AA type of amyloidosis is most common
      and serious complication cause nephropathy and end-stage renal disease (ESRD).
      Renal transplantation (RTX) remains treatment of choice for ESRD. We aimed to
      investigate long-term results of RTX in patients with FMF amyloidosis. PATIENTS
      AND METHODS: We compared the outcomes of 18 patients (12 men and 6 women) with
      FMF amyloidosis among 601 (2.9%) transplants with 200 control patients.
      Demographic data and gene analysis were evaluated. RESULTS: In our study the 1
      year graft and patient survivals were 94.44% and 100%, respectively. At 5 years
      after RTX, they were 94.73% and 88.88%, respectively, in the FMF group without
      difference from controls. Mean creatinine level at 1 and 5 years were 1.43 +/-
      0.54 and 1.73 +/- 0.89, respectively. The results of MEFV mutation analyses were:
      M694V/M694V homozygote in 1 patient, M694V/EQ148 in 3, M694V/V726A in 2, 680M
      I/E148Q in 3, M694V/M680I in 5, R202Q/M680I in 2, and M694V/R202Q in 2.
      Recurrence was noticed in 1 patient with M694V/M680I. One patient died because of
      graft loss and cardiac complications with M694V/M680I gene analysis. Colchicine
      was reduced in 4 patients owing to side effects. CONCLUSION: Long-term outcomes
      of transplantation in patients with amyloidosis secondary to FMF is similar to
      that in the general transplant population and maintenance colchicine, even after
      decreasing its dose, effectively prevents recurrence of amyloidosis in the
      allograft.

PMID- 24314943
TI  - Value of early diethylentriamine penta-acetic acid renograms in predicting late
      allograft outcomes.
AB  - BACKGROUND: Tc-99m-diethylentriamine penta-acetic acid (DTPA) renal scintigraphy
      is useful, noninvasive diagnostic tool for the management and follow-up of the
      transplanted kidney. There have not been any studies of the predictive value of
      DTPA renal scintigraphy for short- and long-term allograft functions. Our aim was
      to reveal the significance of different perfusion-uptake patterns observed on Tc
      99m-DTPA renal scintigraphy for long-term graft outcomes. METHODS: We
      retrospectively analyzed 59 renal transplanted children (30 male and 29 female).
      All patients were underwent DTPA on posttransplant day 7. Perfusion- and function
      related parameters of DTPA (the ratio of peak perfusion counts to plateau counts
      [P:PL], the ratio of counts at peak perfusion to counts at peak uptake [P:U], and
      glomerular filtration rate [GFR] calculated using commercially available
      software) were studied. The mean P:PL and P:U calculated using the half-moon
      shaped background region of interest. A renal time activity curve was generated
      for evaluate perfusion- and function-related parameters. The patterns were
      classified and the value of these early DTPA parameters in predicting long-term
      graft function was analyzed. RESULTS: The mean age of patients was 16.69 +/- 4.77
      years. The mean posttransplant follow-up time was 3.5 +/- 0.4 years. Thirty-nine
      patients received living-related donor allografts and the remaining 20 were from
      deceased donors. Thirteen children suffered >= 1 acute rejection episode. Eight
      patients lost their grafts during follow-up. Mean GFR value at year 3 was 80.61
      +/- 39.03 mL/1.73 m(2) BSA/min. There was a significant difference for mean
      creatinine values at year 3 between recipients with normal perfusion and function
      and normal P:PL with decreased P:U patterns in early DTPA (P < .05). The normal
      P:PL with decreased P:U pattern is associated with lowest GFR value at
      posttransplant year 3. There was also a significant difference for mean GFR
      values at year 3 between recipients with normal perfusion and function and acute
      tubular necrosis (P < .05). Acute rejection episodes and graft loss were mostly
      seen in recipient with a decreased P:PL with or without decreased P:U pattern in
      early DTPA. The decreased P:PL with or without decreased P:U pattern may be
      associated with high risk of acute rejection episodes and graft loss. CONCLUSION:
      Posttransplant early perfusion uptake patterns observed on Tc-99m-DTPA renal
      scintigraphy can be used as a long-term prognostic marker of poor renal outcomes.
      This would permit an opportunity for early intervention.

PMID- 24314944
TI  - The effect of adjuvant H1N1 influenza vaccine on allograft kidney function.
AB  - INTRODUCTION: Administration of the adjuvant influenza vaccine has been suspected
      to increase the risk of allograft rejection; however, not much is known about the
      effect of adjuvant H1N1 vaccination on allograft kidney function. The aim of this
      study was to evaluate the effect of adjuvant H1N1 vaccine on allograft kidney
      function. METHODS: A total of 78 stable kidney transplant recipients were
      enrolled in the study. These patients were vaccinated with a pandemic adjuvant
      H1N1 inactivated intramuscular influenza vaccine. Local and systemic adverse
      reactions occurring for 2 weeks after vaccination were recorded. Serum
      creatinine, creatinine clearance, and 24-hour urine proteinuria were measured
      before and 1 and 3 months and 2.5 years after vaccination. RESULTS: Mean patient
      age was 45 +/- 14 years (range, 21-78 years). Serum creatinine, creatinine
      clearance, and 24-hour urine proteinuria levels were not significantly different
      between before and 1 month after vaccination (1.3 +/- 0.35 vs 1.3 +/- 0.5 mg/dL,
      83 +/- 28 vs 78 +/- 31 mL/min, and 356 +/- 437 vs 293 +/- 307 mg, respectively).
      Serum creatinine level did not differ significantly between before and 2.5 years
      after vaccination (1.3 +/- 0.35 vs 1.4 +/- 0.39 mg/dL; P > .05). No rejection
      episodes occurred during 2.5 years of follow-up. Reported adverse reaction
      frequencies included pain (20%), muscle aches (4%), fever (2.6%), and headache
      (1.3%). CONCLUSIONS: The use of pandemic adjuvant H1N1 influenza vaccination is
      safe in patients after kidney transplantation. However, larger cohort studies
      with longer follow-up periods are needed to confirm this issue.

PMID- 24314945
TI  - Neurocognitive functions in pediatric renal transplant patients.
AB  - Neurocognitive dysfunction is one of the major complications of chronic renal
      failure (CRF). Uremic state during CRF encompasses a wide spectrum of
      neurobehavioral and neurological disturbances. Recent studies showed that the
      pathophysiology of neurocognitive dysfunction in CRF is related to plasma levels
      of uremic solutes. Successful renal transplantation improves renal, metabolic,
      and endocrine functions and the quality of life. The aim of our study was to
      determine the state of neurocognitive function in pediatric renal transplant
      recipients. We prospectively performed a neurological examination and
      neuropsychological test battery (Bender-Gestalt Test, Cancellation Test, and
      Visual and Auditory Number Assay Test) in 20 pediatric renal transplant
      recipients between 6 and 16 years of age. Twenty healthy children and 20 children
      with CRF were included in the study as the control groups. Mean age of the renal
      transplant recipients was 13.50 +/- 3.40 years old. Mean evaluation time after
      transplantation was 2.0 +/- 0.5 years. Bender-Gestalt Test result was abnormal in
      40% of patients. The results of the Cancellation Test and the Visual and Auditory
      Number Assay Test showed significant decline in pediatric renal transplant
      patients when compared with the control. We found that neurocognitive dysfunction
      was frequent in pediatric renal transplantation patients. Awareness of this
      potential problem may be helpful for early recognition and treatment. Our
      findings suggest that periodic neurocognitive assessments may be indicated in
      transplant recipients. 

PMID- 24314946
TI  - Different classifications yield variance in metabolic syndrome prevalence and
      dynamics in renal transplant recipients.
AB  - INTRODUCTION: The metabolic syndrome (MS) is a combination of factors that are
      associated with increased cardiovascular diseases. High MS prevalence was
      reported in renal transplant recipients. However, little is known about the
      longitudinal prevalence and its dynamic properties in this population. We studied
      the longitudinal prevalence of MS at 3 and 12 months post-transplantation using 3
      classifications. PATIENTS AND METHODS: We studied a cohort of 322 patients who
      underwent transplantation between 1996 and 2003 who had isotopic measurement of
      transplant glomerular filtration rate and MS assessment at 3 and 12 months after
      transplantation. Prevalence and change of MS status in terms of acquisition or
      regression were analyzed based on World Health Organization (WHO), International
      Diabetic Federation (IDF), and The Adult Treatment Panel-III (ATP-III)
      classifications. RESULTS: The prevalences at 3 and 12 months were as follows:
      WHO, 8.4% and 8.1%; IDF, 25.8% and 29.8%; and ATP-III, 34.3% and 36.6%,
      respectively. Change in MS status was noted in 9.7%, 16.4%, and 20.5% of subjects
      within WHO, IDF, and the ATP-III classifications, respectively. Prevalence was
      significantly lower with WHO than IDF and ATP-III. Prevalence was the highest
      with ATP-III. However, the difference with IDF was significant only at 3 months
      post-transplantation. Depending on the classification used, 10%-21% of subjects
      change MS status within the first year of transplantation. CONCLUSION:
      Longitudinal analysis confirms the high prevalence of MS and also highlights the
      dynamics of MS. We think both prevalence and dynamics should be accounted for
      when studying outcomes.

PMID- 24314947
TI  - Metabolic syndrome performs better than the individual factors in predicting
      renal graft outcome.
AB  - AIM: Individual components of the metabolic syndrome (MS), especially obesity and
      hypertension, have a deleterious effect on renal graft outcome. Whether MS is
      better than its individual components in predicting the decline of renal function
      is unknown. We studied the presence of MS and its individual components at 12
      months post-transplantation according to the Adult Treatment Panel III
      classification and their influence on measured graft function. METHODS: A cohort
      of 322 patients who underwent transplantation between 1996 and 2003 and who
      agreed to have their glomerular filtration rate (GFR) measured by urinary
      clearance of technetium 99m (Tc*-DTPA) (measured GFR [mGFR]) at 3, 12, 48, 60,
      and 96 months after transplantation were included. The patients were followed up
      until patient death, graft loss, or December 2009 (mean follow-up: 3 +/- 2.8
      years). The linear mixed effect model for longitudinal repeated measures was
      applied. To compare MS versus its components we used the Akaike information
      Criterion (AIC) to determine the best model according to the Anderson and Burnham
      method. RESULTS: Univariate and multivariate analyses models using MS were more
      efficient than those using the individual components, which consisted of waist
      circumference, low high-density lipoprotein-cholesterol, hypertriglyceridemia,
      hyperglycemia, and systolic and diastolic blood pressure. The AIC was the lowest
      with MS models indicating better prediction on graft function than the individual
      components. CONCLUSION: MS is a better predictor of mGFR decline than its
      individual components. It is a valid and precious tool to assess outcomes.

PMID- 24314948
TI  - Cytomegalovirus infection in renal transplant recipients: one center's
      experience.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic viral
      infection that causes morbidity, graft loss, and mortality among renal transplant
      recipients (RTRs). The aim of this study was to evaluate the impact of CMV
      infection on allograft function, graft/patient survival, and the possible
      asssociations between CMV infection and HLA typing. METHOD: This retrospective
      study included 162 RTRs who had at least 1 year regular post-transplantatioin
      follow-up between January 2007 and December 2011. Recipients who had positive
      quantative CMV-polymerase chain reaction (PCR) were assigned to the study group
      (n = 17) and PCR-negative patients were assigned to the control group (n = 145).
      To determine whether CMV infection was related to HLA specificities, the
      incidence of CMV infection was analyzed in relation to HLA-A, -B, and -DR typing.
      RESULTS: Study groups were similar in terms of demographic, clinical, and basal
      laboratory findings. Duration of dialysis before transplantation was
      significantly longer in this study group (P = .018). Although the total HLA
      mismatches of both groups were similar, we found that HLA-B51-positive recipients
      had a lower risk for CMV infection (P = .018). CMV infection was more frequent in
      patients with a double-J stent (P = .001). Although basal creatinine levels of
      the two groups were similar, the study group patients' creatinine levels were
      significantly increased during the 1-year post-transplantation period compared to
      controls (P = .0001). Frequency of acute rejection was significantly higher in
      the study group (41.2% vs 11%, P = .001). Graft loss due to any cause was also
      significantly higher in the study group (29.4% vs 6.9%, P = .01). Patients who
      had preoperative induction therapy and post-transplantatioin tacrolimus-based
      regimens were prone to CMV infection (P = .0001, .006). CONCLUSIONS: Despite
      recent advances in prophylaxis, CMV infection is still a risk factor for RTRs.
      According to our data, long pretransplantation dialysis duration, being HLA-B51
      negative, having a double-J stent, preoperative induction therapy, and post
      transplantation tacrolimus-based regimens might induce development of CMV
      infection by 1-year post-transplantation follow-up.

PMID- 24314949
TI  - Biliary complications after pediatric liver transplantation.
AB  - OBJECTIVES: After liver transplantation, biliary complications are more prevalent
      in pediatric patients, with reported rates varying between 15% and 30%. METHODS:
      We retrospectively analyzed biliary complications observed in 84 pediatric liver
      transplantation patients between July 2006 and September 2012. Biliary
      reconstruction was accomplished via a duct-to-duct anastomosis in 5 (83.3%) of
      the 6 patients receiving whole liver grafts and in 44 (56.4%) of the 78 patients
      who received a segmental live donor graft. For the remaining 34 patients with
      living donor and 1 patient with whole liver graft, Roux-en-Y hepaticojejunostomy
      was the preferred method. RESULTS: Post-transplantation biliary complications
      were encountered in 26 patients (30.1%). The biliary complication rate was 38% in
      49 duct-to-duct anastomosis, whereas it was 20% in the hepaticojejunostomy group
      consisting of 35 recipients. Thirteen of the 18 biliary leaks were from duct-to
      duct anastomoses and the remaining 5 were from the hepaticojejunostomies and 6 of
      the 8 biliary strictures were observed in recipients with duct-to-duct
      anastomosis. In 19 of the 26 patients, the biliary complications were
      successfully treated with interventional radiologic procedures and 1 was treated
      with stent placement during endoscopic retrograde cholangiopancreatography.
      CONCLUSIONS: Percutaneous interventional procedures are valuable, effective, and
      life-saving therapeutic alternatives for the treatment of bile leaks and
      strictures after pediatric liver transplantations.

PMID- 24314950
TI  - Multivisceral transplantation for the treatment of intra-abdominal tumors.
AB  - BACKGROUND: Some intra-abdominal or retroperitoneal tumors such as low-grade slow
      growing malignancies may seem unresectable due to major vessel encasement or
      presence of intra-abdominal dissemination, but the slow growth rate and to some
      extent long life expectancy of the patients urge us to find some strategies to
      cure the patients or at least achieve tumor remission or symptom palliation. En
      bloc resection, followed by multivisceral or liver-sparing "modified"
      multivisceral transplantation has recently been used for treatment of these
      patients. RESULTS: Between May 2010 and October 2012, 3 multivisceral and 3
      modified multivisceral transplantations were performed in 6 patients (aged 14 to
      55 years; mean, 32 years) with some slow growing intra-abdominal malignancies (2
      neuroendocrine tumors, 2 gastrointestinal stromal tumors, 1 desmoid tumor, and 1
      low-grade sarcoma). All patients survived the procedure. One patient died of
      pancytopenia 2 months after transplantation and another died with pulmonary
      emboli at 4 months. The remaining 4 patients are alive without any evidence of
      disease recurrence. CONCLUSIONS: Although large intra-abdominal desmoid tumors,
      well-differentiated neuroendocrine tumors, and gastrointestinal stromal tumors
      are slow growing, they tend to invade locally, especially to the mesenteric root
      and/or celiac axis and other abdominal viscera. Complete resection followed by
      multivisceral transplantation could be a therapeutic option for these advanced
      tumors.

PMID- 24314951
TI  - Efficacy of recruitment maneuver for improving the brain dead marginal lungs to
      ideal.
AB  - BACKGROUND: Because of the shortage of lungs for transplantation, finding the
      suitable lungs in brain-dead donors is an important issue. Recruitment maneuver
      is a strategy aimed at re-expanding collapsed and edematous lung tissue. The aim
      of this study was to assess the efficacy of this maneuver on improving marginal
      lungs for transplantation. METHODS: From 127 brain-dead potential donor which
      were evaluated for lung donation in Masih Daneshvari Organ Procurement Unit of
      Tehran, Iran, 31 (25%) had marginal lungs for transplantation. These donors had
      normal chest X ray or bilateral infiltration and had PaO2 200-300 mm Hg with FIO2
      100%. The recruitment maneuver was performed and arterial blood gas was obtained
      before and after maneuver. The maneuver lasts for 2 hours with continuous check
      of O2 saturation and patient's hemodynamic during. Finally, patients with normal
      bronchoscopy and PaO2/FIO2 >300 mm Hg were considered good candidates for lung
      transplantation. The frequency (%) and mean +/- SD were used for description of
      variables and the Wilcoxon test was used for comparison between pre- and post
      maneuver PaO2 with FIO2 100%. RESULTS: The mean +/- SD of PaO2/FIO2 with 100%
      FIO2 of patients before and after recruitment were 239 +/- 62 and 269 +/- 91,
      respectively. Recruitment maneuver could convert 10 marginal lungs (32%) to
      appropriate ones (PaO2 > 300) and finally 8 lungs were transplanted. CONCLUSIONS:
      Findings of this study showed that recruitment maneuver could convert
      inappropriate lungs to appropriate ones in one third of brain-dead patients who
      had marginal lung condition. So, it is recommended that this maneuver is
      considered in the assessment protocol of lungs for donation.

PMID- 24314952
TI  - RIFLE criteria for acute kidney dysfunction following heart transplantation:
      incidence and risk factors.
AB  - BACKGROUND AND PURPOSE: There are few data regarding the occurrence of (RIFLE)
      based acute kidney dysfunction (AKD) after heart transplantation (HT) and its
      risk factors. The aim of this study was to apply RIFLE criteria in patients who
      developed AKD following HT to compare patients with and without AKD and to
      determine incidence and risk factors of AKD. PATIENTS AND METHODS: We
      retrospectively analyzed the records of 65 patients who underwent HT between 2003
      and 2012. We investigated 3 levels of renal dysfunction outlined in RIFLE
      criteria: risk (R), injury (I), and failure (F). Appropriate class was assigned
      comparing baseline creatinine level to peak levels in the first 7 days after HT.
      Perioperative variables of heart transplant recipients were collected. RESULTS:
      The mean age at transplantation was 32.8 +/- 16.6 years with 72.7% males. The
      incidence of AKD was 61%, risk occured in 18%, injury in 16%, and failure in 27%
      of the patients. Patients who had AKD were significantly older (37.9 +/- 15.6 vs
      24.6 +/- 15.0 years: P = .008), had higher body mass index (24.7 +/- 6.7 vs 18.6
      +/- 4.3; P = .002), and more frequently had history of hypertension (92% vs 8%; P
      = .011) and smoking (100% vs 0%; P = .008) when compared with those who did not
      have AKD. When compared with patients who did not develop AKD postoperatively,
      preoperative higher creatinine levels (1.1 +/- 0.3 vs 0.8 +/- 0.4; P = .025),
      intraoperative higher mean arterial pressures (99.2 +/- 14.1 vs 89.0 +/- 11.4 mm
      Hg; P = .011), a higher frequency of intraoperative acidosis (81% vs 19%; P =
      .041), higher lactate levels (5.1 +/- 3.8 vs 2.8 +/- 1.7 mmol/L; P = .038), and
      postoperative more frequent use of cyclosporine (91% vs 9%; P = .025) were seen
      in those who developed AKD. Logistic regression analysis revealed that age (odds
      ratio [OR], 1.057; 95% confidence interval [CI], 1.010-1.106; P = .018) and use
      of cyclosporine (OR, 0.099; 95% CI, 0.010-0.935; P = .043) were independent risk
      factors for AKD. CONCLUSIONS: Our results suggest that based on RIFLE criteria,
      AKD occur in more than half of HTs postoperatively. Older age and use of
      cyclosporine are associated with AKD following HT.

PMID- 24314953
TI  - The prevalence and course of pulmonary hypertension and right ventricular
      dysfunction in patients undergoing orthotopic heart transplantation.
AB  - BACKGROUND: Pulmonary hypertension (PHT) and right ventricular (RV) dysfunction
      are among the commonly observed and potentially serious complications following
      heart transplantation. RV dysfunction is reported to occur in as much as half of
      these patients. In this study, the authors sought to examine the prevalence and
      the course of these prognostically important complications. METHODS: The records
      of 30 patients who had undergone orthotopic heart transplantation at our center
      were examined. Demographic and clinical variables were noted; RV dysfunction,
      pulmonary artery pressure on Doppler echocardiographic examination, and catheter
      findings were recorded. RESULTS: The mean age of the study population was 31.3
      years. On preoperative assessment, PHT was present in 21 (70%) patients. The
      average value of systolic pulmonary artery pressure was 44.5 +/- 5.9 mm Hg. The
      mean value of pulmonary vascular resistance was 3.3 +/- 1.8 hybrid reference unit
      (HRU). RV dysfunction was detected on postoperative assessment in 17 (56.7%)
      patients. The mean ischemia time was 216 +/- 77 minutes; in 3 cases it exceeded 5
      hours but in none of the cases did it reach 6 hours. Rejection was detected in 14
      (46.7%) patients. Most of the patients received inotropic agents in the early
      postoperative period. When compared with preoperative values, on follow up at the
      end of the first year, a significant decrease in pulmonary artery pressure was
      observed (47.4 +/- 4.8 vs 38.5 +/- 7.5 mm Hg; P = .03), and the ratio of patients
      experiencing RV dysfunction decreased to 16.6% (n = 5). CONCLUSION: The findings
      of this study indicate that RV dysfunction and PHT are common complications
      following heart transplantation and improve with appropriate management over time
      with monitoring.

PMID- 24314954
TI  - Curcumin attenuates renal ischemia and reperfusion injury-induced restrictive
      respiratory insufficiency.
AB  - OBJECTIVE: Pulmonary failure, instead of kidney failure, is one of the leading
      causes of acute kidney injury (AKI)-related death. Volume overload was previously
      regarded as the primary cause of lung injury, presumably by impaired renal fluid
      clearance. Recent evidence suggested that proinflammatory cytokines, chemokines,
      and free radicals released during AKI are playing a crucial role in the lung
      injury. We aimed to examine the protective efficacy of lung function with
      curcumin pretreatment. METHODS: AKI was induced by 45 minutes of kidney ischemia
      (bilateral occlusion of renal pedicles) followed by 3 hours of reperfusion. Rats
      were divided into 3 groups: sham-operated, kidney ischemia and reperfusion (I/R),
      and a group with 2 days of oral pretreatment with curcumin (12.5 mg/kg/d) before
      I/R injury. The pulmonary function test (PFT) was conducted at baseline and after
      3 hours of reperfusion, yielding parameters of lung volumes, chord compliance
      (Cchord), inspiratory resistance (RI), and forced expiratory volume at the first
      200 millisecond (FEV200). We also examined levels of protein concentration (PC),
      methylguanidine (MG), tumor necrosis factor-alpha (TNF-alpha), and
      malondialdehyde (MDA) in the bronchoalveolar lavage (BAL). RESULTS: Ischemic AKI
      induced restrictive lung disease was demonstrated by the decreased Cchord, total
      lung capacitance (TLC), and FEV200, in addition to the increased lavage PCBAL,
      MG, TNF-alpha, and MDA level. Curcumin pretreatment ameliorated lung function
      impairment and alveolar vascular protein leak and attenuated lung inflammation.
      CONCLUSIONS: The protective effect of curcumin pretreatment against restrictive
      lung disease is most likely associated with decreasing hydroxyl radical, lipid
      peroxidation, and inflammation in the lungs and improving alveolar vascular
      permeability.

PMID- 24314955
TI  - Curcumin treatment protects against renal ischemia and reperfusion injury-induced
      cardiac dysfunction and myocardial injury.
AB  - OBJECTIVES: Renal ischemia and reperfusion (I/R) injury frequently leads to acute
      renal failure (ARF) and multiple-organ injury with a substantial morbidity rate.
      The primary cause of ARF-associated death is, however, cardiac failure instead of
      renal failure itself, and the pathogenesis of renal I/R-induced cardiac injury is
      still poorly understood. We evaluated the efficacy of curcumin pretreatment on
      cardioprotection. METHODS: Thirty Sprague-Dawley rats were evenly divided into 3
      groups of sham-operated control, renal I/R injury, and a curcumin pretreatment
      group. Renal ischemia was conducted by bilateral occlusions of pedicles for 45
      minutes, followed by 3 hours of reperfusion. The cardiac function was assessed by
      the left ventricular end-systolic-pressure-volume-relation (ESPVR), systolic
      pressure (SP), ejection fraction (EF), and stroke volume (SV). Myocardial injury
      was assessed based on creatine kinase muscle brain fraction (CK-MB) and Troponin
      I (cTnI), and kidney injury was assessed based on blood urea nitrogen (BUN) and
      creatinine. We also assessed the levels of tumor necrosis factor-alpha (TNF
      alpha) and malondialdehyde (MDA) in the heart tissues. RESULTS: SV, EF, and SP
      reduced moderately during the ischemic phase with no major change in ESPVR.
      During reperfusion, SV, SP, and ESPVR initially increased, and then steadily
      decreased. Myocardial and kidney injury were marked by the increases in serum CK
      MB and cTnI, and creatinine and BUN level. Curcumin pretreatment ameliorated
      ESPVR and attenuated injuries of both the heart and kidney resulting from I/R
      insult. CONCLUSIONS: Curcumin pretreatment improved cardiac contractility and
      attenuated myocardial and renal injury through reducing inflammatory response in
      the kidney and heart and oxidative stress in the myocardium.

PMID- 24314956
TI  - N-acetylcysteine improves cardiac contractility and ameliorates myocardial injury
      in a rat model of lung ischemia and reperfusion injury.
AB  - OBJECTIVES: Lung ischemia and reperfusion (I/R) injury is the major complication
      subsequent to cardiopulmonary bypass surgery and lung transplantation. Lung I/R
      injury frequently induces cardiac dysfunction leading to significant mortality.
      So far, the literature on therapeutic interventions in cardiac dysfunction and
      myocardial injury is still scarce. In this study, we examined the efficacy of N
      acetylcysteine (NAC) administration against lung I/R injury-induced cardiac
      dysfunction. METHODS: Lung ischemia was established by occluding the left lung
      hilum for 60 minutes, followed by 2 hours of reperfusion. Studies were performed
      in 3 groups: sham-operated (same surgical procedure except vessel occlusion; N =
      8), lung I/R injury (N = 12), and NAC-administered group (N = 12). The cardiac
      function was assessed using simultaneous left ventricular (LV) pressure and
      volume measured via a high-fidelity pressure-volume catheter. Myocardial injury
      was assessed based on serum creatine kinase muscle brain fraction (CK-MB) and
      troponin I (cTnI) level, and lung injury based on the degree of protein
      concentration in lung lavage. We also examined the degrees of myocardial lipid
      peroxidation and hydroxyl radical production with and without NAC. RESULTS:
      During lung ischemia, LV stiffness increased with relative intact contractility.
      After 2 hours of reperfusion, LV contractility decreased with dilated and
      stiffened ventricle, along with apparent myocardial and lung injury. NAC
      administration effectively attenuated heart and lung injury, and ameliorated
      impaired LV contractility and stiffening resulting from lung I/R injury.
      CONCLUSIONS: NAC administration reduced lung I/R-induced increases in myocardial
      hydroxyl radical production and lipid peroxidation, and ameliorated LV
      contractility and stiffening.

PMID- 24314957
TI  - Early-onset posterior reversible encephalopathy syndrome after solid organ
      transplantation in pediatric patients: a report of 2 cases.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a neurological disturbance
      that occurs due to different reasons and presents with different clinical
      symptoms. It can be a devastating situation, but, timely treatment may lead to
      complete recovery. We report 2 cases of PRES, which developed and fully recovered
      in the early period after solid organ transplantation in pediatric patients. 

PMID- 24314958
TI  - The 8th Congress of the Andalusian Society of Organ and Tissue Transplantation
      (SATOT).

PMID- 24314959
TI  - Application of game-like simulations in the Spanish Transplant National
      Organization.
AB  - Twenty years ago, the Spanish National Transplant Organization (NTO) started a
      management and organizational system, known as the Spanish Model, that has
      allowed the NTO to occupy a privileged world position regarding deceased donation
      rates, which have been 33-35 donors per million population in recent years. One
      of the key elements of this model is its instructional approach. Two years ago,
      the NTO started the project "educ@nt" in close collaboration with the e-UCM
      research group of the University Complutense of Madrid to support and maximize
      its successful professional training system. As a result, 3 game-like simulations
      have been developed representing the different procedural steps of the
      suprahospital level of the transplantation process. These simulations represent
      the donor and organ evaluation, the allocation of organs applying the
      corresponding geographic and clinical criteria, and the logistics of
      transportation. Simulations are based on 10 representative teaching cases that
      help students become familiar with the most common cases arriving in the NTO. For
      the 2nd consecutive year, these simulations have been used in different courses
      around Spain.

PMID- 24314960
TI  - Shipping impact on liver graft: results of liver transplantation program in
      Andalusia.
AB  - Liver transplantation for the treatment of patients with advanced liver disease
      is organized according to a waiting list taking into account different criteria.
      The agreed distribution model in Andalusia assumes that sometimes an organ is
      extracted in a different province to that where the implantation is to be
      performed (shipping), which, therefore, increases the graft ischemic time. The
      aim of the present study was to determine whether transportation of the organ and
      being harvested by a team other than the implantation team have a negative effect
      on final patient survival. 

PMID- 24314961
TI  - Serologic behavior of S100B protein in patients who are brain dead: preliminary
      results.
AB  - OBJECTIVE: The objective of this study is to assess the S100B protein serum
      concentrations from brain dead (BD) donors to understand whether its level could
      provide clinical information during BD diagnosis as a potential confirmatory
      test. METHODS: During 12 months, 26 patients declared BD were prospectively
      included in this study. Once the diagnosis of BD was achieved, serum S100B
      protein levels were measured using an electrochemiluminescence assay. For
      analytical purposes, we selected the maximum S100B serum value reached during the
      first 5 days of evolution from a historical cohort of 124 survived patients after
      a severe brain injury (SBI), as well as from 18 healthy donors (HD) and a
      subgroup of patients who had severe traumatic brain injuries (TBIs) without
      extracranial injuries. RESULTS: Mean age was 53.48 years (SD, 18.91 years). The
      BD group had significantly higher S100B serum levels (1.44 MUg/L; interquartile
      ratio [IR], 0.63-3.68) than the SBI (0.34 MUg/L; IR, 0.21-0.60) and HD groups
      (0.06 MUg/L; IR, 0.03-0.07; P < .001). Analysis of S100B levels depending on the
      main cause responsible for BD development showed significant differences between
      subgroups (P = .012). S100B serum levels were higher in the isolated TBI BD group
      (P = .004). The S100B value showed an odds ratio for BD diagnosis of 8.38 (95%
      confidence interval [CI], 1.16-60.45; P = .035). Reciever operating
      characteristic analysis revealed an area under the curve of 0.92 (95% CI, 0.79
      1.00; P = .007). We set a cut-off value of 2 MUg/L in S100B serum concentrations.
      At this level, the diagnostic properties of S100B would reach 100% of specificity
      and positive predictive value (PPV), and sensitivity and negative predictive
      value (NPV) of 60% and 86.7%, respectively. CONCLUSION: This preliminary analysis
      shows for the very first time that BD is associated with higher S100B serum
      levels, compared with other neurocritical care patients. We also found that the
      cause of BD development must be considered. Specifically, S100B serum levels in
      severe isolated TBI patients-with clinical exploration compatible with BD-could
      be used in a future as confirmatory test.

PMID- 24314962
TI  - Experience of the transplant unit from Virgen de las Nieves Hospital in using
      liver grafts from asystolic donors.
AB  - Given the shortage of donors, it has become increasingly necessary to use
      alternative sources to meet the growing demand for organs, and evolution in the
      use of asystolic donors is proving to be an important resource in helping to meet
      those needs. The goal of this study is to describe the initial results of our
      experience with Type II asystolic donation. An observational retrospective study
      was conducted to analyze the variables of four cases in this type of donation.
      After the analysis we conclude that, despite the limited number of cases in our
      series, the results are compatible with larger series and permit us to continue
      to value this method as a resource for broadening the donor pool. 

PMID- 24314963
TI  - Attitudes of Scottish residents in the southeast of Spain concerning living
      donation.
AB  - BACKGROUND: To reduce the considerable organ deficit, living donation is being
      promoted. The subset of foreign population living in Spain could be potential
      patients for transplantation and/or donation. The objective of this study was to
      analyze the attitudes toward living donation (LD) of the population from the
      southeast of Spain who are natives of Scotland. MATERIALS AND METHODS: Within the
      "International Collaborative Donor Project," a random representative sample was
      obtained of the adult population residing in the southeast of Spain and who were
      born in Scotland (n = 350). Attitudes were evaluated with the use of a validated
      questionnaire that was completed anonymously and was self-administered. The
      Student t test, chi(2) test, and Fisher exact test were applied. RESULTS: The
      completion rate was 93% (n = 324); 90% of the respondents (n = 290) were in favor
      of related LD, decreasing to 26% (n = 85) if it was unrelated. In the analysis of
      variables affecting attitude toward LD, differences were found in: 1) attitude
      toward deceased donation (P < .001); 2) having had previous experience of the
      donation and transplantation process (P = .049); 3) a respondent's belief that
      his or her religion was in favor of LD (P < .001); and 4) a partner's attitude
      toward donation and transplantation (P = .007). CONCLUSIONS: The attitude toward
      related LD among Scottish residents in the southeast of Spain is very favorable,
      and is very closely related to attitude toward deceased donation, family
      attitude, and religious attitude. Patients on the waiting list of Scottish origin
      will be one of the most appropriate groups for promoting LD when living donation
      is being promoted in Spain.

PMID- 24314964
TI  - Factor analysis of sources of information on organ donation and transplantation
      in journalism students.
AB  - BACKGROUND: Journalists and the information they disseminate are essential to
      promote health and organ donation and transplantation (ODT). The attitude of
      journalism students toward ODT could influence public opinion and help promote
      this treatment option. OBJECTIVE: The aim of this study was to determine the
      media through which journalism students receive information on ODT and to analyze
      the association between the sources of information and psychosocial variables.
      METHODS: We surveyed journalism students (n = 129) recruited in compulsory
      classes. A validated psychosocial questionnaire (self-administered, anonymous)
      about ODT was used. Student t test and chi(2) test were applied. RESULTS:
      Questionnaire completion rate was 98% (n = 126). The medium with the greatest
      incidence on students was television (TV), followed by press and magazines/books.
      In the factor analysis to determine the impact of the information by its source,
      the first factor was talks with friends and family; the second was shared by
      hoardings/publicity posters, health professionals, and college/school; and the
      third was TV and radio. In the factor analysis between information sources and
      psychosocial variables, the associations were between information about organ
      donation transmitted by friends and family and having spoken about ODT with them;
      by TV, radio, and hoardings and not having spoken in the family; and by TV/radio
      and the father's and mother's opinion about ODT. CONCLUSIONS: The medium with the
      greatest incidence on students is TV, and the medium with the greatest impact on
      broadcasting information was conversations with friends, family, and health
      professionals. This could be useful for society, because they should be provided
      with clear and concise information.

PMID- 24314965
TI  - Irish citizens resident in the southeast of Spain and xenotransplantation.
AB  - BACKGROUND: It is fundamental to find out the level of social acceptance of
      xenotransplantation (XT), especially in areas where there are preclinical
      projects. In the native population in the southeast of Spain this situation is
      well known, but in recent years there has been a considerable social change due
      to large migratory flows, especially concerning Ireland. The aim of this study
      was to analyze the attitude toward XT among the population in the southeast of
      Spain born in Ireland and to determine the variables affecting this attitude.
      METHODS: Within the "International Collaborative Donor Project," a random sample
      was taken (n = 325) of the population from the southeast of Spain born in
      Ireland. Attitude was evaluated using a validated questionnaire, which was self
      administered and completed anonymously. RESULTS: The questionnaire completion
      rate was 82% (266 respondents of the 325 selected). Regarding animal organ
      donation for humans, if the results were similar to those achieved using human
      donors, 62% (n = 165) would be in favor, 30% (n = 79) undecided, and the
      remaining 8% (n = 22) against. If the results were worse than those achieved
      using human donors, 20% (n = 50) would be in favor, 59% (n = 150) undecided, and
      the remaining 21% (n = 54) against. Attitude toward XT is related to religion (P
      = .003), knowing the favorable attitude of one's religion toward transplantation
      (P = .037), having spoken about donation and transplantation within the family (P
      = .001), a partner's favorable attitude toward transplantation (P = .001), and a
      favorable attitude toward both deceased (P = .001) and living (P = .023) human
      donation. CONCLUSIONS: Attitude toward XT among Irish citizens who are resident
      in the southeast of Spain is worse than that of the native Spanish population and
      is mainly determined by factors related to prior attitude toward the different
      types of human organ donation, family attitude, and religious motives.

PMID- 24314966
TI  - Knowledge of the brain death concept among adolescents in southeast Spain.
AB  - BACKGROUND: The concept of brain death (BD) is not very well known in the
      population, making it one of the main psychosocial barriers to favorable
      attitudes toward donation. Adolescents are a key sector of the population for
      future organ donation. For this reason it is important to find out what they know
      about this concept. OBJECTIVES: The aim of this study was to analyze the concept
      of BD among adolescents in the southeast of Spain and to determine their
      influence on attitude toward organ donation. METHODS: In the southeast of Spain a
      random sample was stratified according to Compulsory Secondary Education (CSE)
      schools. In the 10 selected schools, we performed a random sampling of each of
      the classes from the 1st to the 4th years of CSE. Knowledge of the concept of BD
      and attitude toward donation were analyzed with the use of a validated
      questionnaire, which was self-administered and completed anonymously. Statistical
      analyses used the Student t test and the chi(2) test. RESULTS: Of 3,547
      adolescents surveyed, 38% (n = 1,337) of the respondents knew the BD concept,
      considering it to be the death of an individual. Of the rest, 54% (n = 1,930) did
      not know this concept and the remaining 8% (n = 280) thought it did not mean a
      person's death. The respondents who were more in favor of deceased donation had a
      better knowledge of the concept of BD than those who had doubts (40% vs 35%,
      respectively; P = .007). The knowledge of the concept of BD was associated with
      variables directly and indirectly related with donation and transplantation (P <
      .05). CONCLUSIONS: Most adolescents in the southeast of Spain do not know the
      concept of BD, and this adversely affects the attitude toward organ donation.

PMID- 24314967
TI  - Information received by secondary school teaching personnel about organ donation
      and transplantation: a study in the southeast of Spain.
AB  - BACKGROUND: Information about organ donation and transplantation (ODT) is the
      basis on which attitude toward this subject is shaped. The information about ODT
      that teachers can provide to school children is fundamental for them to develop a
      favorable attitude to this matter in the future. OBJECTIVES: The aims of this
      study were: 1) to determine the type of information on ODT received by secondary
      school teachers; 2) to determine through which means teachers obtain information
      about donation; and 3) to determine the influence of each information source on
      their attitudes. METHODS: A sample was selected from 10 secondary schools, which
      were geographically stratified in southeast Spain. A validated questionnaire was
      applied about attitude toward ODT among teachers (n = 327), which was completed
      anonymously and was self-administered. The statistical analysis used the Student
      t test and the chi-square test. RESULTS: The questionnaire completion rate was
      88% (n = 288); 99% (n = 286) of the responding teachers stated that they had
      received some information about ODT, and 40% (n = 117) indicated that they had
      good or very good information. The teachers received information about ODT from
      several sources, the most frequent being audiovisual means: television (89%),
      press (60%), and radio (47%). Social/family means were also important, such as
      conversations with other people (51%) and conversations with family members
      (39%). Teachers who reported having good information were more in favor of ODT
      than those who had limited or no information (P = .001). Only the exchange of
      information through conversations with family members was related to a positive
      attitude (P = .009). CONCLUSIONS: Most secondary school teachers in southeast
      Spain receive information about ODT. However, fewer than half think that the
      information is good. Teachers receive information through different means,
      especially audiovisual means, mainly television. Nevertheless, the social/family
      means has the most influence on attitude.

PMID- 24314968
TI  - Incidence of post-transplantation lymphoproliferative disease in Andalusia (1990
      2009).
AB  - BACKGROUND: Post-transplantation lymphoproliferative disease (PTLD) is a severe
      complication of renal transplantation (RT) but information about its incidence
      and predisposing factors is diverse, varying according to geographic area and
      study period. METHODS: We analyzed the incidence of PTLD after all RT performed
      at adult transplantation centers in Andalusia from January 1, 1990 to December
      31, 2009, recorded in the Andalusian Transplant Co-ordination Information System
      (SICATA) regional computerized database (n = 5577). We calculated the risk of
      PTLD using the Kaplan-Meier curve, censoring for organ failure and incidence rate
      per patient-year of exposure. Log-rank comparisons were made by center (n = 5),
      decade (1990-1999 vs 2000-2009), age group, recipient gender, hepatitis C virus
      (HCV) serology, transplantation number, and duration of pre-RT replacement
      therapy (per quartiles). RESULTS: We identified 60 cases of PTLD. The pre-RT
      treatment time was 48.2 +/- 60 months; 11.7% were retransplantations, and 10.4%
      had a positive HCV serology. The median post-RT time before diagnosis of PTLD was
      5.98 years. At the time of the database analysis, only 11 patients (18%) were
      alive with a functioning transplant; 10% had returned to dialysis and 72% had
      died. The actuarial incidence of PTLD at 1, 5, 10, and 20 years post-RT was 0.2%,
      0.5%, 1.6%, and 2.9%, respectively; the exposure rate was 14.71 PTLD/10,000
      patient-years (95% confidence interval [CI], 12.3-17.1). Although the incidence
      tended to be higher in 1990-1999 than 2000-2009 (16.8 vs 12.1 cases/10,000
      patient-years), in the actuarial study the difference was far from significant
      (at 7.5 years, 1.2 vs 0.8%; P = .4). Nor were there significant differences in
      the curves of incidence per RT center (1%-1.2% of patients) or recipient
      characteristics. CONCLUSIONS: The cumulative incidence of PTLD in Andalusia in
      patients with a functioning kidney transplant during 1990-2009 was 2.9% at 20
      years. There was no significant variation between the RT centers or over time. No
      associated factors were identified among the basic recipient variables studied.

PMID- 24314969
TI  - Outcomes in renal transplantation with expanded-criteria donors.
AB  - BACKGROUND: Kidney transplantation is the treatment of choice for patients with
      end-stage renal disease. In recent years donor criteria have changed to increase
      the percentage of expanded-criteria donors (ECDs). The aim of this study was to
      analyze transplants from ECDs obtained at our institution from. 2010 to 2012. We
      studied the comorbidity of ECD, preimplantation histologic study, renal function,
      and survival of transplanted grafts. PATIENTS AND METHODS: Eighty ECDs (160
      kidneys) were analyzed. Forty-nine grafts were not implanted owing to macroscopic
      lesions (37 kidneys) or histologic findings on preimplantation biopsy (12
      kidneys). Finally, 60 grafts from ECDs were implanted in our center. We analyzed
      the characteristics of the grafts (kidney function, creatinine clearance) and
      compared the data with a control group of allografts from standard-criteria
      donors (n = 14). RESULTS: The median age of the ECD group was 72 years (range 65
      77). No differences were found in certain characteristics between the ECDs whose
      kidneys were or were not implanted (hypertension, diabetes, creatinine at the
      time of the donation or proteinuria). However, there were differences in donor
      age (75 vs 67; P = .043), increased preimplantation biopsy score (6.8 +/- 1.3 vs
      4.8 +/- 1.1; P = .041), and a higher percentage of cardiovascular disease (62.5%
      vs 43%; P = .038). Comparison of ECD and non-ECD grafts showed a lower creatinine
      clearance at 1 year (50 +/- 05 mL/min vs 69 +/- 96 mL/min, respectively; P <
      .001) and 2 years (50 +/- 07 mL/min vs 67 +/- 74 mL/min; P < .001) after
      transplantation. There were no differences in delayed graft function or graft
      survival between the 2 groups at 2 years after transplantation (95% vs 100%; P =
      .38). CONCLUSIONS: We found no differences in graft survival from ECD compared
      with the control group of standard-criteria donors. The evaluation of grafts from
      ECD may be a strategy to increase the number of kidney transplants.

PMID- 24314970
TI  - Long-term allograft survival after kidney transplantation.
AB  - BACKGROUND: Technical and medical advances over the past few years have produced
      an important increase in the functionality of renal allografts. The aim of this
      study was to identify the factors associated with allograft survival 15 years
      after transplantation in our series. METHODS: A retrospective study of kidney
      transplantations was carried out at Reina Sofia Hospital in Cordoba from February
      1979 to December 1997, with follow-up through June 2012. A subanalysis of the
      series was undertaken, and Kaplan-Meier analysis and Cox proportional hazards
      model regression used to achieve the main objective of the study. RESULTS: A
      total of 487 renal allografts with a mean follow-up of 114 months were studied,
      of which 37% (n = 180) survived for >15 years. Of the 180 patients, the main
      causes of graft failure were chronic allograft nephropathy in 29 (66%) and
      patient death in 13 (29.5%). Multivariate analysis identified the number of HLA
      mismatches (hazard ratio [HR] 1.25, 95% CI 1.01-1.56), panel reactive antibodies
      (HR 2.61, 95% CI 1.28-5.26), and delayed graft function (HR 11.25, 95% CI 1.33
      95.28) as being significantly associated with graft loss after 15 years.
      CONCLUSIONS: The high immunologic risk of the patients was independently
      associated with graft loss. Delayed graft function was the most important factor
      in the speed of graft failure beyond 15 years.

PMID- 24314971
TI  - Variations in initial renal transplant function by type of organ retrieval.
AB  - BACKGROUND: Numerous factors have been associated with early delay in kidney
      function and thence the graft survival. However, few data are derived from
      different types of donation: single or multiorgan. Our goal was to analyze the
      association of type of retrieval with the early function of the renal graft.
      METHODS: A retrospective analysis of transplantations performed in the Reina
      Sofia Hospital from January 2004 to June 2012 from local deceased donors was
      carried out. We performed a descriptive analysis of the variables and univariate
      and multivariate analyses with the use of logistic regression to determine the
      association of type of retrieval (kidney-only [KO], kidney-liver [KL], and
      multiorgan [MO]) with delayed graft function (DGF) and early graft failure (EGF).
      RESULTS: We analyzed 287 kidney transplantations from 182 deceased donors, of
      which 25 (13.7%) were KO, 80 (43.9%) KL, and 77 (42.3%) MO. DGF was higher in MO
      retrievals compared with KL and KO (25.8% vs 24% vs 20.5%), though without
      reaching significance (P = .81). EGF at 3 months was 17.6% in KO compared with
      10.5% in KL and 5.3% in MO (P = .2). Regarding DGF, in the multivariate analysis,
      donor age (P = .049) and donor sex (P = .029) appeared to be related to DGF.
      There were no differences by type of retrieval. Multivariate logistic regression
      analysis established a significant relationship between KO retrieval and EGF at 3
      months (P = .005) compared with MO. CONCLUSIONS: Early graft function at 3 months
      decreases when the allograft is from KO retrievals compared with MO, probably
      related to the more unfavorable characteristics of these donors and their
      corresponding recipients.

PMID- 24314972
TI  - Correlation between dual kidney biopsy in expanded-criteria donors and transplant
      survival.
AB  - OBJECTIVE: The aim was to study the relation between same-donor renal biopsies
      and analyze whether the score influences graft survival. METHODS: We
      retrospectively reviewed histologic results of expanded-criteria donors and the
      graft survival in patients followed at Reina Sofia Hospital (Cordoba, Spain) from
      January 2004 to October 2012. We analyzed clinical and demographic variables from
      the donors, as well the association between the scores of same-donor biopsies who
      had different scores for each kidney and the graft survival with a t test for
      paired data. A Kaplan-Meier with log-rank test was performed between the higher
      score and the lower-score groups. We excluded retransplantation and those who
      received a combined transplantation (liver or pancreas). RESULTS: We analyzed 168
      kidneys that had been biopsied, from 84 donors. Of the whole sample, 35.7% (n =
      30) had the same score for each kidney, whereas 64.3% (n = 54) had discrepancies.
      In this second group, 81.8% (n = 44) had a difference of 1 point, and the
      remaining 18.2% (n = 10) had a larger difference. Both kidneys were suitable for
      transplantation in 72.7% of cases (n = 40), only 1 in 14.5% (n = 8), and none in
      12.7% (n = 7). For analyzing the survival of the paired kidneys there were 48
      kidneys from 24 donors with a different score for each kidney. We observed a
      difference in favor of the better scores, with a difference of 11 months up to
      the time of the analysis (P = .045). We found no significant differences in the
      log-rank test between the survival rate for the group with a less favorable score
      (95% confidence interval [CI], 61.26-95.67) versus those with a more favorable
      score (95% CI, 66.76-93.03). CONCLUSIONS: A high percentage of biopsies had a
      different score for the 2 kidneys from the same donor. This difference was
      important for graft survival. We therefore recommend doing a biopsy of both
      kidneys.

PMID- 24314973
TI  - Pancreas graft survival in simultaneous pancreas-kidney versus pancreas-after
      kidney and pancreas alone transplantations: a single institution experience.
AB  - BACKGROUND: Pancreas transplantation offers excellent outcomes today in patients
      who have type-1 diabetes mellitus (DM) with difficult control in terms of
      increasing patient and pancreatic graft survival. Different factors in donors,
      recipients, and the perioperative period have been associated with long-term
      graft survival. The aim of this study was to compare pancreatic graft survival in
      simultaneous pancreas-kidney transplantation (SPK) and the other two modalities,
      pancreas-alone and pancreas-after-kidney transplantation (non-SPK), at our
      institution. METHODS: This retrospective cohort study included 63 pancreas
      transplantation patients from January 2007 to May 2012 at our institution. The
      patients were divided into two groups: SPK and non-SPK transplantations. We
      excluded those patients who had transplants with vascular graft loss. The primary
      endpoint was 1-year and overall graft survival with consideration of multiple
      relevant variables. Non-parametric tests were calculated with the statistical
      package SPSS 20 (SPSS INC, Chicago, IL). RESULTS: The 1-year and overall graft
      survival in this period was 87.3% and 82.5%, respectively. The median follow-up
      was 963 days. The causes of graft loss were vascular (64%) and immunologic (34%).
      Finally, we included 56 pancreas transplantations, 46 (82%) were SPK and 10 (18%)
      non-SPK. The donor and recipient characteristics were similar in both groups,
      except for the duration of DM (SPK 22 years vs. non-SPK 29 years) and recipient
      body mass index (SPK 23 vs. non-SPK 28); P = .042 and P = .003, respectively. The
      cold ischemia time was 563 minutes (standard deviation, 145). Bivariate analysis
      showed that long-term graft loss was only influenced by matching for gender (P =
      .023). Using the Kaplan-Meier method, the pancreas graft survival was better in
      SPK than in non-SPK transplants (log rank .038). CONCLUSIONS: Patients who
      receive pancreas-alone or pancreas-after-kidney grafts have shorter long-term
      graft survival. Multiple strategies should be applied to improve immunologic
      surveillance and obtain an early diagnosis of graft rejection.

PMID- 24314974
TI  - Study of renal function in living kidney donors: estimated or measured glomerular
      filtration.
AB  - INTRODUCTION: In living kidney donations the accuracy of renal function is
      fundamental, especially for potential donors who have limited renal function
      (creatinine clearance levels [CCr] <90 mL/m/1.73 m(2)), are >50 years old, and
      who have cardiovascular risk factors that might favor the development of kidney
      diseases. OBJECTIVE: To compare the direct measured glomerular filtration (mGFR)
      using 51Cr-EDTA and the estimations based on creatinine (estimated glomerular
      filtration rate [eGFR]): CCr with 24-hour urine, and estimated using Cockroft
      Gault (adjusted using body surface area, Mosteller formula), modification of diet
      in renal disease-4 (MDRD-4), MDRD-6, and Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) to determine the usefulness of different methods to
      evaluate the kidney function. PATIENTS AND METHODS: The kidney function
      evaluation was performed for 37 potential kidney donors using the 51Cr-EDTA
      method. The GFR obtained through the 51Cr-EDTA was compared with the CCr values
      in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD-4, MDRD-6,
      and CKD-EPI). RESULTS: Using the Bland Altman graph, the most dispersed results
      were obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of
      Passing and Bablok, MDRD-4 and MDRD-6 showed the highest approximation to the
      reference method proposed to be substituted, whereas CCr showed a high
      dispersion. CONCLUSION: The eGFR using MDRD-4 and MDRD-6 formulas revealed the
      best adjustment to the measure by 51Cr-EDTA. This might represent the best option
      if a direct eGFR measure is not available.

PMID- 24314975
TI  - Evolution of quality of life in renal transplant recipients and patients with
      multiple sclerosis: a follow-up study.
AB  - OBJECTIVE: We aimed to compare the evolution of quality of life in 2 medical
      conditions under immunotherapy (cadaveric renal transplantation [G1] and multiple
      sclerosis [G2]), and to assess the clinical significance of the results compared
      with a representative age-adjusted sample of the general Spanish population (G3).
      METHODS: Using a mixed design (2 * 2), the SF-36 Health Survey was administered
      to 60 patients with one of these clinical conditions (30 in each group; the
      patient group factor), matched for gender, and homogenized regarding age and
      working status. All renal patients had undergone transplantation 6 months before
      the first assessment, and all neurological patients presented a relapsing
      remitting course and a mild-moderate disability level. Both patient groups were
      assessed a second time 6 months later (the phase factor). A mixed analysis of
      covariance was computed controlling for age as a covariate. Cohen's d was
      reported as an effect size index and to analyze the clinical significance
      regarding a representative age-adjusted sample of the general Spanish population
      (n = 5821). RESULTS: Statistically significant differences were found between
      patient groups in vitality, bodily pain, social functioning, and mental health (P
      < .01), in which worse levels were displayed by patients with multiple sclerosis
      in both phases (Cohen's ds1-2 from 0.61 to 1.40). Likewise, an interactive effect
      was observed in physical functioning [F(1,57) = 12.93; P = .001], such that the
      performance of daily physical activities improved in renal recipients after 6
      months, but it decreased in neurological patients. Patients with multiple
      sclerosis showed higher, clinically significant impairment in all SF-36
      dimensions in both phases compared with renal recipients (Cohen's ds2-3 from 
      0.50 to -1.61), who presented clinically significant impairment in general
      health, role-physical, and role-emotional (Cohen's ds1-3 from -0.73 to -1.28).
      CONCLUSIONS: Renal transplant recipients need specialized health care 1 year
      after transplantation because they still display relevant impairment in daily
      functioning compared with the general population.

PMID- 24314976
TI  - Predictive factors of infection in the first year after kidney transplantation.
AB  - BACKGROUND: Infectious disease, a complication favored by immunosuppression, is
      the main cause of 1st-year mortality in solid organ transplantation. In renal
      transplant recipients (RTRs), urinary tract infection (UTI) is the most common,
      and the microorganisms that are isolated depend on chronology. METHODS: We
      present an observational study comprising 129 RTRs from January 2010 to December
      2011 who were followed during the 1st year after transplantation. We analyzed
      occurrence of infections, predisposing factors, timing, severity, site of
      infection, and microorganisms. RESULTS: The patients had a total of 424
      infectious episodes during the 1st year (3.29 episodes/patient/year). The
      predominant focus was the urinary tract, with at least 1 episode in 69.8% of
      patients. Bacteremia was recorded in 25.6% of patients and surgical wound
      infection in 20.9%. Cytomegalovirus infection or disease was diagnosed in 46.5%.
      Severe infections occurred in 30.2%. The predominant pathogen was E. coli. There
      was a significant correlation between hospital stay and the number of infections
      (P = .000; r = 0.407) and between body mass index and hospital stay (P = .001; r
      = 0.282). Severe infections were more frequent in diabetics, patients with a
      double-J stent, and those treated with basiliximab. Patients with cytomegalovirus
      replication had a higher number of infections (4.1 +/- 1.2 vs 2.5 +/- 5; P =
      .000) and significantly higher annual serum creatinine (1.65 +/- 5.7 vs 1.31 +/-
      1.3 mg/dL; P = .003). CONCLUSIONS: The prevalence of infections in the 1st year
      after kidney transplantation is very high, occurring mainly in the early period,
      in the urinary tract, and due to E. coli. Cytomegalovirus replication is
      associated with a higher number of infections and higher serum creatinine at 1
      year. Body mass index is a predictor of early infection and of bacteremia in the
      post-transplantation period. Basiliximab induction and having a double-J stent
      were predictors of severe infections.

PMID- 24314977
TI  - Associated characteristics and impact on survival of post renal-transplantation
      lymphoproliferative disease: case-control study from a regional registry.
AB  - BACKGROUND: Lymphoproliferative disease (LPD) after renal transplantation (RT) is
      an unusual complication but one that impacts greatly on survival. We examined
      possible predisposing factors and their effect on survival using data from the
      Andalusian Transplant Co-ordination Information System (SICATA) regional
      computerized database of patients on renal replacement therapy due to chronic
      kidney disease (CKD). METHODS: The study population comprised all RT undertaken
      at adult centers in Andalusia from January 1, 1990 to December 31, 2009 (N =
      5577). We retrospectively analyzed cases at December 31, 2011 (N = 60). A control
      group comprised the 2 closest RT in time done at the same center and with equal
      or greater graft survival at the time of diagnosis of LPD in the associated case
      (N = 120). The basic variables were obtained from the general register (1990
      2009) and widened from the specific register (2000-2009). Case-control comparison
      of survival was done with Kaplan-Meier from diagnosis to death or organ loss
      censored for death. Cox univariate and multivariate (LPD plus available
      covariables of demonstrated effect) analyses were done. RESULTS: We found no
      significant differences between cases and controls regarding the characteristics
      of the recipient or of the donor/organ, initial immunosuppression by intention to
      treat, or post-RT course. The impact on recipient survival 5 years after
      diagnosis was as follows: LPD, 35%; controls, 90% (P < .000). Cox univariate
      analysis showed the relative risk (RR) of death for LPD was 11.36 (95% confidence
      interval [CI], 6.2-20.9; P < .000) and the multivariate analysis showed relative
      risk (RR) = 13.87 (7.45-25.3; P < .000). The impact on death-censored graft
      survival 5 years after diagnosis was as follows: LPD, 65%; controls, 87% (P =
      .007). Cox univariate analysis was as follows: RR of failure for LPD, 2.70 (95%
      CI, 1.3-5.7; P = .009). CONCLUSIONS: We found no significant differences between
      LPD cases and contemporary controls regarding the basic characteristics of the
      recipient, donor/organ, initial immunosuppression, or initial graft evolution.
      There was an enormous impact on both patient and graft survival.

PMID- 24314978
TI  - Proteinuria as a predictive factor in the evolution of kidney transplantation.
AB  - INTRODUCTION: Certain factors can change the course of renal transplantation,
      such as acute rejection, ischemia time, and compatibility. Other donor and
      recipient factors may modify this evolution. Proteinuria modifies glomerular
      disease progression and may influence renal graft survival. In this study we
      analyzed proteinuria in patients who received a transplant since 2000 in
      Andalusia. MATERIAL AND METHODS: We studied the Andalusian Renal Transplant
      Registry from January 2000 to March 2012, recording data on 1815 patients who had
      proteinuria, registered at the third month and first year after transplantation.
      Three groups were formed, including those with proteinuria < 300 mg/24 h, those
      between 300 and 1000 mg/24 h, and those >1000 mg/24 h. RESULTS: At the third
      month and the first year after transplantation, 65.7% and 71.6% of patients had
      proteinuria < 300 mg/24 h, 29.6% and 24.1% had proteinuria between 300 and 1000
      mg/24 h, and 4.7% and 4.4% had proteinuria > 1,000 mg/24 h, respectively. We
      found differences between the three proteinuria groups in panel reactive
      antibodies (% PRA), serum creatinine at the third month and the first year, the
      etiology of the donor death, incidence of delayed renal function, and incidence
      of hypertension. The degree of proteinuria influenced graft and patient survival.
      In multivariate analysis, proteinuria was an independent risk factor for renal
      graft loss CONCLUSIONS: The degree of proteinuria at the third month and the
      first year after transplantation is predictive of graft and patient survival. The
      patients who had more proteinuria at the third and 12th month after
      transplantation had worse renal function and more hypertension. Proteinuria is an
      independent risk factor for renal graft loss.

PMID- 24314979
TI  - Patients with terminal chronic liver pathology faced with this disease.
AB  - BACKGROUND: "Anxious preoccupation" is a maladaptive coping strategy for patients
      with terminal chronic liver pathology causing psychopathologic emotional
      responses. The aim of this study was to identify "anxious preoccupation" as a
      coping strategy when faced with this disease and to investigate its relationship
      with emotional-type psychopathologic symptoms in patients awaiting a liver
      transplant (LT). METHODS: A total of 63 patients awaiting an LT were evaluated.
      The instrument used to evaluate coping style was the Mental Adjustment to Cancer
      questionnaire. One of the coping scales of this questionnaire is "anxious
      preoccupation" (9 items). An Instrument for psychopathologic assessment was used,
      the SA-45 questionnaire, which assessed 9 psychopathologic dimensions:
      somatizations, obsessions-compulsions, interpersonal sensitivity, depression,
      anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. RESULTS:
      "Anxious preoccupation" was used as an inadequate coping style by 51% of patients
      when faced with the disease. Five psychopathologic dimensions were associated
      with this coping strategy: 1) obsessive-compulsivity: 75% of patients with
      "anxious preoccupation" had obsessive-compulsivity symptoms compared with 29% of
      patients with other coping strategies (P < .001); 2) interpersonal sensitivity:
      25% vs 6%, respectively (P = .044); 3) depression: 59% vs 29% (P = .015); 4)
      anxiety: 75% vs 32% (P = .001); and 5) phobic anxiety: 19% vs 3% (P = .050).
      CONCLUSIONS: More than one-half of the patients on the LT waiting list used
      "anxious preoccupation" as a coping style for this disease. This strategy was
      associated with a greater presence of emotional-type psychopathologic symptoms in
      these patients.

PMID- 24314980
TI  - Donor characteristics that are associated with survival in liver transplant
      recipients older than 70 years with grafts.
AB  - INTRODUCTION: The use of grafts from donors older than 70 years of age is
      increasing due to the decrease in the number of donors and the increase in
      waiting list patients. MATERIAL AND METHODS: We undertook a univariate and
      multivariate analysis of 980 adult recipients of whole liver grafts, 129 of them
      from donors aged 70 years or older. RESULTS: No differences were found in patient
      survival compared with recipients of younger grafts. There were no higher rates
      of rejection, vascular or biliary complications, postoperative bleeding, or
      infections, but older grafts were associated with graft dysfunction (P = .01) and
      a higher frequency of postoperative refractory ascites (P = .007), but without a
      greater need for retransplantation. As graft-associated factors, the joint
      presence in the donor of diabetes (P = .00; confidence interval [CI] = 0.04
      0.117), hypertension (P = .00; CI = 0.22-0.39), and weight of more than 90 kg (P
      = .031; CI = 0.05-0.104) were suggestive of poor prognostic factors in recipient
      survival. Survival in hepatitis C virus (HCV) recipients or recipients aged older
      than 60 years was worse with donors aged older than 70 years, although not
      significantly so. With grafts from donors aged older than 80 years (n = 15),
      although patient survival rate was good (70% at 10 years), there was a higher
      rate of retransplantation (20%) and the early mortality rate was 13.3%.
      CONCLUSIONS: Use of grafts from donors aged older than 70 years is safe, with
      similar survival to patients with younger grafts. The appearance of initial
      dysfunction with prolonged ascites may be due to a delay in reaching a correct
      functionality, but was not associated with increased mortality, complications, or
      need for retransplantation. It should also be avoided in recipients older than 60
      years or with HCV. Grafts older than 80 years were associated with a good long
      term patient survival but at the expense of a higher rate of retransplantation.
      However, it helps to reduce the time on the waiting list and, thus, mortality. We
      noted decreased survival associated with donor hypertension, diabetes, and
      obesity, so these donors should be selected more rigorously.

PMID- 24314981
TI  - Is "intra-operating room" thromboelastometry useful in liver transplantation? A
      case-control study in 303 patients.
AB  - Coagulation monitoring during liver transplantation (LT) is, even today,
      fundamental to reduce blood loss during surgery. Thromboelastometry (TEM) is a
      proven technique for controlling the various parameters that influence
      coagulation. However, there are no studies linking "intra-operating room" TEM
      (orTEM) with LT outcomes. We describe a case-control study in 303 liver graft
      recipients analyzing variables associated with operative complications and long
      term LT outcomes. The results showed that orTEM reduced the use of blood products
      in patients with Model for End-Stage Liver Disease scores of >= 21,
      retransplantation, and high surgical difficulty and important intraoperative
      bleeding. In addition, results in survival and postoperative complications were
      better when orTEM was used. In conclusion, we confirm that use of orTEM is
      associated with less use of blood products and a lower rate of complications
      after LT.

PMID- 24314982
TI  - Combined liver-kidney transplantation: survey of a single center in Spain.
AB  - BACKGROUND: Renal dysfunction is a common complication of advanced liver failure
      and liver transplantation. Since the introduction of the MELD criteria the
      proportion of patients with advanced chronic kidney disease and need for liver
      transplantation has increased. One alternative is the combined liver-kidney
      transplant (CLKT). The aim of this study was to evaluate the outcome of this type
      of transplant in our center. METHODS: We retrospectively analyzed all combined
      simultaneous or sequential transplants from 1989 to 2012. We studied demographic
      and clinical variables. Survival analysis was performed by Kaplan-Meier method.
      RESULTS: In the study period, 1,265 kidney and 1,050 liver transplantations were
      performed; 34 were CLKT (to 29 adults and 5 children); 13 of these were
      simultaneous and 12 sequential liver-kidney. We also carried out 4 triple liver
      pancreas-kidney transplantations, 3 simultaneous and 1 sequential. The mean age
      was 44.1 +/- 15 years, and 27 were male (93.1%); 9 (37.5%) were diabetic. The
      main causes of liver disease were viral (n = 11 [41.3%; hepatitis virus B, C, or
      both] and alcoholism (9 [31%]). The renal disease etiology was unknown in 16
      (55.1%), IgA nephropathy in 2 (6.8%), membranoproliferative glomerulonephritis in
      2 (6.8%), and calcineurin inhibitor toxicity in 4 (13.6%). Transjugular renal
      biopsy was performed in 6 sequential transplants. Survival of patients who
      received a CLKT was excellent: 91%, 51%, and 40%, at 1, 5, and 10 years,
      respectively. No significant difference was found between sequential and
      simultaneous transplants (log rank 0.5). CONCLUSIONS: Our results of CLKT show
      results similar or superior to those of other series and are an alternative to
      consider in candidates for liver transplantation with chronic kidney disease.
      Transjugular biopsy is an alternative to study the etiology of renal disease in
      patients with hepatic dysfunction before or after liver transplantation.

PMID- 24314983
TI  - Liver transplantation using low-weight recipients from a graft split program.
AB  - We present our experience with a split liver (SL) program shared with the
      children's liver transplantation (LT) program from 2 different hospitals in the
      use of partial grafts from cadaver donors in brain death. We describe an
      observational, retrospective study, which included patients who underwent a SL
      transplantation in our center between January 2006 and December 2012. Clinical
      variables were recorded of both donors and recipients and their data were
      analyzed using SPSS 19.0 software. Of a total of 204 LT, 4 (2%) patients were
      treated with a SL. The causes of LT were alcoholic cirrhosis in 2 cases,
      cryptogenic cirrhosis, and primary biliary cirrhosis (PBC). In all cases there
      was a temporary portocaval shunt. The confluence of the hepatic veins of the
      recipient was anastomosed to the donor vena cava and arterial anastomosis was
      performed. The reconstruction was hepato-choledochal in all cases. There were no
      cases of postreperfusion syndrome or vascular thrombosis and no retransplantation
      was necessary. Currently, 3 of the 4 cases are still alive. Death in the other
      patient was due to mesenteric ischemia. Our center has participated in the
      development of a protocol that considers the indication of this technique
      provided expert groups are involved in its development, regardless of hospital
      level. This will expand the pool of donors and partially solve the current
      problems with available grafting.

PMID- 24314984
TI  - Results of liver transplants from donors aged 70 plus: analysis of Andalusian
      transplant register.
AB  - The progressive increase in the number of liver transplantation candidates has
      brought with it a consequent increase in waiting list mortality, making it
      necessary to revise donor selection criteria and to analyze the factors that
      optimize outcomes. This retrospective observational study of 1802 liver
      transplantations performed in Andalusia between 2000 and 2010 analyzes the
      outcomes from donors aged 70 years or older (n = 211) in terms of survival rates
      of the graft and the recipient, the type of transplant, donor age, and DMELD
      (Donor-Model for End-Stage Liver Disease) score. The most frequent reasons for
      transplantation were alcoholic cirrhosis (45.5%), hepatitis C cirrhosis (20.4%),
      and liver cancer (11.8%). The overall survival rate at 5 years was 67%; with a
      significant decrease in survival rates for recipients with a DMELD greater than
      1400 (44%). In the 70-year-old-plus donor group, the overall patient and graft
      survival rates were 57% and 52%, respectively. The re-transplantation rate
      increased proportionately with donor age: 5.9% between 70 and 74 years, 9.5% from
      75 to 79 years, and 17.6% from 80 to 84 years. In the alcoholic cirrhosis
      recipient sub-group, the overall survival rate at 5 years was 69% (P < .05)
      compared to 34% in hepatitis C patients (P < .05). The widening of the donor age
      selection criteria is therefore a safe option, provided that a DMELD score less
      than 1400 is obtained. Although re-transplantation rates increase progressively
      with donor age, they remain less than 10%. It is necessary to carefully screen
      recipients of older organs, taking into account that the best results are
      obtained for patients who have alcoholic cirrhosis, are hepatitis C negative, and
      have a DMELD score that is less than 1,400.

PMID- 24314985
TI  - Study of liver transplant rejection in alcoholism-induced cirrhosis.
AB  - Rejection is the most usual cause of primary dysfunction of hepatic allograft
      transplants. Acute rejection (AR) often occurs in the early post-transplantation
      weeks, with an incidence of 12%-19%. Chronic rejection (CR) is less usual (2.5%
      17%) and irreversible. Our aim was to determine the incidence of AR and CR in
      patients who underwent transplantaton due to alcoholism-induced cirrhosis and the
      survival of these groups. We undertook a retrospective study of the 93 patients
      who received a liver transplant due to hepatic cirrhosis between 2005 and 2012.
      AR occurred in 23.7% of cases, and CR in 11.8%. The median time from implantation
      to the appearance of AR was 34.5 days, and for CR it was 334 days. The survival
      of the patients with AR and CR showed no significant differences as compared with
      the control group (P = .77). From our clinical appraisal, symptoms of previous AR
      may lead to CR, although the relationship was not significant.

PMID- 24314986
TI  - Longitudinal study of liver transplant recipients' quality of life as a function
      of their perception of general health: at waiting list and at 3, 6, and 12 months
      post-transplantation.
AB  - OBJECTIVE: The objective of this study was to compare the evolution (at waiting
      list, and at 3, 6, and 12 months post-transplantation) of quality of life of
      cadaveric liver transplant recipients as a function of their perception of
      general health. METHODS: Two groups (15 patients with better and 15 with worse
      self-perception of health 1 year after transplantation) were assessed at the
      pretransplantation and post-transplantation phases using the EuroQol (EQ-5D)
      questionnaire. Mixed analysis of covariance was performed with 2 factors: phase
      (at waiting list and at 3, 6, and 12 months post-transplantation) and perception
      of general health (better and worse). Cohen's d was also calculated. RESULTS:
      Interactive effects were found in the variables pain/discomfort (P = .010) and
      anxiety/depression (P = .001). The following simple effects reached large effect
      sizes. Transplant recipients presented more pain/discomfort when on the waiting
      list than at 3 months (worse self-perception, P = .022, d = 1.35; better self
      perception, P = .001, d = 0.95). At 6 months (P = .001, d = -1.45) and at 12
      months (P = .001, d = -1.75), transplant recipients with worse self-perception
      displayed more pain/discomfort. Transplant recipients with better self-perceived
      health showed more anxiety/depression when on the waiting list than at 3 months
      (P = .004, d = 1.49), at 6 months (P = .005, d = 1.48), and at 12 months (P =
      .001, d = 1.97). Patients with worse self-perception presented more
      anxiety/depression when on the waiting list than at 6 months (P = .030, d = 1.21)
      and 12 months compared with at 3 months (P = .011, d = -0.97) and 6 months (P =
      .001, d = -1.39). At 12 months, transplant recipients with worse self-perception
      showed more anxiety/depression (P = .001, d = -2.18). CONCLUSION: Pain/discomfort
      and, especially, anxiety/depression contribute to liver transplant recipients'
      worse general health status 1 year after transplantation.

PMID- 24314987
TI  - Evolution of anxious-depressive symptomatology in liver and kidney transplant
      recipients: hospitalization and 12-month post-transplantation phases.
AB  - OBJECTIVE: The objective of this study was to compare the evolution
      (hospitalization in the transplantation unit and at 12 months post
      transplantation) of anxious and depressive symptomatology in cadaveric transplant
      recipients as a function of type of organ implanted (liver or kidney). METHODS:
      Using a 2 * 2 mixed factorial design, 2 groups were selected: 34 liver transplant
      recipients and 41 kidney transplant recipients. Both groups were assessed in 2
      phases: (1) in the transplantation unit after discharge from the intensive care
      unit; and (2) 12 months after discharge from the hospital following implantation
      surgery. The Hospital Anxiety and Depression Scale and the Scale for the
      Assessment of Social Support were administered. A mixed analysis of covariance
      was used to assess the influence on transplant recipients' anxious-depressive
      symptomatology of 2 independent factors: phase (hospitalization in the
      transplantation unit and at 12 months post-transplantation) and organ (liver and
      kidney). Perceived social support and age were included as covariates in the
      analyses. We also calculated d and w as effect size indexes. RESULTS: Interactive
      effects of the factors phase and organ were found in the variable anxiety (P =
      .005). Specifically, the following simple effects were significant: (1) kidney
      transplant recipients presented more anxious symptomatology while hospitalized in
      the transplantation unit than at 12 months post-transplantation (P = .001; d =
      0.52; medium effect size); and (2) kidney transplant recipients presented more
      anxious symptomatology than liver transplant recipients while hospitalized in the
      transplantation unit (P = .013; d = -0.59; medium effect size). No statistically
      significant effect was obtained for the variable depression. CONCLUSION: Worse
      mental health (anxious symptoms) was associated with kidney transplant recipients
      but not with liver recipients while recovering from the implantation surgery in
      the transplantation unit.

PMID- 24314988
TI  - Implantable cardioverter defibrillator for primary prevention in patients with
      severe ventricular dysfunction awaiting heart transplantation.
AB  - BACKGROUND: Despite an increase in patients with end-stage heart failure, the
      acceptance rate has been going down in recent years owing to a change in donor
      demographics. Furthermore, the rate of emergency heart transplantation has
      progressively increased. The result is an increase in the time awaiting heart
      transplantation in elective patients and therefore in the risk of sudden death in
      this population. Implantable cardioverter defibrillators (ICDs) could be a
      preventive option in these cases. However, indications for the implantation in
      this population are not well established. OBJECTIVE: We sought to evaluate the
      effectiveness of ICDs for primary prevention in patients with left ventricular
      ejection fraction (LVEF) <= 30% included on the heart transplantation list.
      METHODS: Records from patients accepted for heart transplantation in our
      institution from January 1, 2006, to July 30, 2012, and whose LVEF was <31% were
      reviewed. Patients who received ICDs for primary prevention (n = 28) were
      compared with patients without ICDs (n = 51). Descriptive and univariate (chi(2)
      and t tests) statistics and Kaplan-Meier survival curves were used for analyses.
      RESULTS: With a median follow-up of 77 days (range 1-1,231), the overall
      mortality in the ICD group was 7.1% (2/28) and in the non-ICD group was 17.6%
      (9/51; P = .062). The main cause of death in patients without ICDs was sudden
      death (5/9, 55.6%), followed by heart failure (4/9, 44.4%). In patients with
      ICDs, heart failure was the only reported cause of death. Appropriate ICD
      therapies were recorded in 42.9% (12/28) in this population. CONCLUSIONS: This
      study suggests that ICD could reduce the risk of sudden death in patients with
      LVEF <= 30% while awaiting heart transplantation. However, more studies are
      needed to confirm these results.

PMID- 24314989
TI  - Medication adherence in patients who undergo cardiac transplantation.
AB  - BACKGROUND: Heart transplant patients are required to take medication for life,
      both immunosuppressants to prevent rejection and any required for other
      illnesses. Treatment compliance can be measured quantitatively or qualitatively.
      Compliance measurement is not easy owing to different factors. The aim of this
      study was to assess the prevalence of therapeutic compliance in heart transplant
      patients. METHODS: We undertook a cross-sectional observational descriptive
      study. The sample comprised patients who received a heart transplant from 2001 to
      2011. Of the 203 patients in total, we studied 99. We used the Morisky-Green test
      as an indirect method and recorded the immunosuppressant blood levels as a direct
      method. RESULTS: The mean age of the patients was 50 +/- 12 years, and 84% were
      male. According to the Morisky-Green test, 33% of the patients were noncompliant,
      of whom 30% said they rarely forgot to take their medication. Patients took an
      average of 8 +/- 3 drugs per day, but only 85% knew what the drugs were for; 24%
      of the patients had grade 3A rejection, and 65% had graft vessel disease.
      CONCLUSIONS: Transplanted patients in this study showed a high level of
      therapeutic adherence that did not differ from other transplant series, either
      cardiac or other organs, nor from other chronic diseases. The results for
      defaulters were higher than that expected from these patients. The defaulter
      results were expected to be lower, given the information that the patients were
      supposed to have, both before and after the transplantation, and with the strict
      medical monitoring. Therefore, we have to stress therapeutic compliance, both
      medical and dietary-hygiene measures, and seek new strategies to improve the
      results.

PMID- 24314990
TI  - Improvement over the years of long-term survival in high-risk lymphoma patients
      treated with hematopoietic stem cell transplantation as consolidation or salvage
      therapy.
AB  - The role of hemopoietic stem cell transplantation (HSCT) is not well established
      in certain types of lymphoma, such as those with a high relapse risk or relapsing
      after initial therapy. New chemotherapeutic schemes and immunotherapy have
      improved survival of these patients. Nevertheless, there is not enough evidence
      regarding whether transplantation is the best therapeutic approach. Moreover,
      published data on long-term follow-up of high-risk lymphoma patients treated with
      HSCT are scarce. We analyzed 177 consecutive patients diagnosed with a high risk
      of relapse or with relapsed lymphoma who underwent HSCT after induction with
      standard chemotherapy in a tertiary academic center from 1989 to 2013. The median
      age was 40 years. Diagnoses were Hodgkin disease (n = 56), diffuse large B-cell
      lymphoma (n = 44), follicular lymphoma (n = 29), mantle cell lymphoma (n = 15), T
      cell lymphoma (n = 18), and others (n = 15). Patients received either an
      autologous graft (n = 154) in first complete remission (1CR; n = 59) or more
      advanced stages (AS; n = 95), or an allogeneic graft (n = 23) in 1CR (n = 4) or
      AS (n = 19). In the autologous group, overall survival (OS) at 5 years was 57%
      and 75% in the periods 1989-2001 and 2002-2013, respectively (P = .05). Patients
      receiving an allogeneic graft presented an OS of 25% and 43% in the 2 periods.
      With a mean follow-up of 5 years (95% confidence interval 3.5-6.6), for patients
      receiving a transplant in 1CR, OS at 5 years was 80%, and for those receiving a
      transplant in AS it was 59% (P = .003). Nonrelapse mortality (NRM) at 5 years was
      3.1% in the autologous group and 27.9% in the allogeneic group (P < .001). The
      main cause of NRM was infection (44%) in the whole cohort. All this leads to the
      conclusion that transplantation, as a therapeutic strategy, has shown a high long
      term OS in this subgroup of patients with such a poor prognosis. OS improved over
      the years and reaching 1CR was a good prognostic feature. Infections were the
      main cause of NRM.

PMID- 24314991
TI  - Fifteen years of follow-up of a liver transplant recipient with glycogen storage
      disease type Ia (Von Gierke disease).
AB  - Von Gierke's disease or glycogen storage disease type Ia (GSD-Ia) is an
      infrequent metabolic disease caused by an atypical accumulation of glycogen. The
      principal cause of this pathology is deficiency of the glucose-6-phosphatase
      enzyme. Herein we have reported a case of a young man with a history of Von
      Gierke's disease (GSD-Ia) since childhood who developed hepatocellular
      adenomatosis brought to light by ultrasounds and TACs. The patient began to
      develop early chronic renal failure, necessitating simultaneous liver and kidney
      transplantation. Years later continuous reviews at the nephrology and
      hepatobiliopancreatic surgery services show he has a good quality of life and a
      normal hepatorenal profile. 

PMID- 24314992
TI  - Modigraf administration through jejunostomy in liver transplant recipient: case
      report.
AB  - We report our experience with a 61-year-old patient with alcoholic and hepatitis
      C cirrhosis who underwent liver transplantation. On the 3rd postoperative day he
      presented a mediastinitis secondary to esophageal perforation produced by a
      Linton tube. An esophagectomy with jejunostomy was performed. Tacrolimus granules
      for oral suspension (Modigraf) were administered through the jejunostomy. This
      case report highlights the use of Modigraf and the absence of secondary effects.
      We observed biochemical parameters during the jejunostomy period. We discuss the
      administration strategy applied and whether tacrolimus granules for oral
      suspension by jejunostomy affect the bioavailability and its side effects.

PMID- 24314993
TI  - Severe heart failure due to noncompaction cardiomyopathy: a case report.
AB  - Noncompaction cardiomyopathy involves an infrequent pathology whose diagnosis has
      been rising in recent years owing to a better understanding of the disease and,
      therefore, better diagnosis. Today, there are no well established protocols for
      its treatment. For this reason, it is necessary to adapt the therapy of choice to
      each patient. We report the case of a 35-year-old man with no past medical
      history of interest who was admitted due to acute pulmonary edema. Diagnostic
      tests revealed noncompaction cardiomyopathy with biventricular severe systolic
      dysfunction. In this situation, heart transplantation was considered to be the
      best therapeutic option, which was carried out with an uneventful postoperative
      course. This is one of the few cases reported in the literature for this issue.

PMID- 24314995
TI  - Increasing living donor kidney transplantation numbers in Budapest.
AB  - Living related kidney donations (LRD) have had a significant impact on therapy of
      kidney diseases. Due to their ease of scheduling in the general surgery program
      and better half-life of about 21.6 versus 13.8 years for deceased donor kidneys,
      this approach has revolutionized nephrology and transplantation medicine. Since
      the first Hungarian LRD which was performed in 1974 in Budapest, Hungary,
      donations have expanded especially in the last 3 years. This has been followed in
      2000 by living unrelated kidney donations (LURD). Since 2000 LURD can be also
      performed in Hungary. From the 251 LRD in our country in the last 3 years, 79
      living donations have accounted for nearly one-third of the cases. In comparison
      of 2008, and 2011 the absolute numbers of LRD as well as LURD have more than
      doubled from 9 to 20 and 6 to 14 respectively. Based on international ranking
      data from the global observatory on donation and transplantation Budapest has
      improved from 1.20 in 2000 to 6.20 LRD per million persons (p.m.p.) in 2010. The
      increase in LURD has also led to some side effects: an increase in recipient age
      from 26 years in 2000 to 46 in 2011 and greater HLA mismatches. In 2010, Budapest
      ranked higher than Croatia or Portugal but still behind Germany (8.13 LRD p.m.p.)
      and the leading countries: the Netherlands (28.49 LRD p.m.p.) and Norway (16.94
      LRD p.m.p.). Because of the tremendous progress in LRD, the gap between today's
      leading countries and Budapest is closing.

PMID- 24314996
TI  - Noninvasive perioperative monitoring of arterial function in patients with kidney
      transplantation.
AB  - Development of atherosclerosis is accelerated in kidney transplant recipients.
      Impaired metabolic pathways have a complex effect on the arterial wall, which can
      be measured by noninvasive techniques. Few data are available on the change of
      stiffness parameters in the postoperative course, so in this study we analyzed
      the stiffness parameters of kidney transplant recipients during the perioperative
      period. Seventeen successful primary kidney transplant patients with uneventful
      postoperative period (7 woman, 10 men; 46.16 +/- 12.19 years) were involved in
      our short-term prospective longitudinal study. We analyzed the correlation
      between noninvasively assessed stiffness parameters (pulse wave velocity [PWV],
      augmentation index [AIx], pulse pressure [PP], systolic area index, diastolic
      area index, diastolic reflection area), ankle-brachial index (ABI), and
      laboratory parameters (creatinine, glomerular filtration rate, urea, haemoglobin,
      C-reactive protein). Stiffness parameters were measured with a Tensiomed
      Arteriograph. These parameters were assessed before the transplantation, and 24
      hours, and 1 and 2 weeks after surgery under standard conditions. We found that
      creatinine (P = .0008) and C-reactive protein (P = .006) serum levels decreased,
      and glomerular filtration rate increased significantly (P = .0005). We revealed
      that PWV (P = .0075) and AIx (P = .013) improved significantly. There was no
      significant change in ABI, PP, and the other monitored parameters. Along with the
      available data in the literature, our findings suggest that kidney
      transplantation has a positive effect on the arterial function.

PMID- 24314997
TI  - Relationship between serum paraoxonase and homocysteine thiolactonase activity,
      adipokines, and asymmetric dimethyl arginine concentrations in renal transplant
      patients.
AB  - Paraoxonase lactonase activity protects against homocysteinylation; therefore, it
      can be a potential contributing factor to prevent atherosclerosis. We aimed to
      determine paraoxonase and HTLase activities and to clarify the relationship
      between HTLase activity and some cardiovascular risk factors, such as
      homocysteine, cystatin C asymmetric dimethylarginine (ADMA), and adipokines both
      in hemo dialyzed and transplanted patients. Among 114 hemodialyzed, 80
      transplanted and 64 healthy control subjects, we investigated body mass index
      (BMI) as well as fasting serum contents of urea, uric acid, creatinine, cystatin
      C, homocysteine, glucose, lipids, total protein and albumin. Serum paraoxonase
      (PON 1) and HTLase activities were measured spectrophotometrically. ADMA, ADPN
      adiponectin, leptin (LEP) levels was determined with a sandwich enzyme-linked
      immunosorbent assay method. Dyslipidemic patients showed hypercholesterolemia,
      and high low-density lipoprotein (LDL); parallel with improved renal function,
      they displayed decreased cystatin C and homocysteine levels (P < .001). There was
      a significant negative correlation between PON 1 activity and cystatin C and
      homocysteine concentrations (P < .05). Obese patients revealed significantly
      higher LDL (P < .05) and leptin concentrations (P < .01). There was a significant
      positive correlation between PON 1 activity and adiponectin levels (P = .0276).
      Both dialyzed and transplanted patients displayed significantly lower HTLase
      activities compared to the control group (P < .001), particularly lower HTLase
      and PON 1 activities in dialyzed subjects compared with the transplanted group (P
      < .05). HTLase activity showed significant negative correlations with ADMA levels
      among the whole study population (P < .001), whereas positive associations were
      noted between PON 1 and HTLase activities (P < .001). HTLase activity may be a
      new predictor of cardiovascular risk in renal failure although it is modulated by
      other risk factors.

PMID- 24314998
TI  - Retransplantations in the Hungarian liver transplant program.
AB  - Retransplantation of the liver (ReOLT), not infrequent consequence of
      transplantation, was analyzed from 512 patient records between 1995 and 2012. The
      34 cases (33 secondary and 1 tertiary). Of ReOLT all employed cadaveric donor
      organs. The 34 reOLT were performed in 31 adults and 3 children. The original
      indication for OLT, among these patients was usually primary sclerosing
      cholangitis (PSC) and acute liver failure (ALF): there were no alcoholic liver
      disease (ALD) patients. The indication for early reOLT (within 3 months) was
      hepatic artery thrombosis while the late reOLTs beyond 3 months after primary
      transplantation was nonanastomotic biliary stenosis. The cumulative patient
      versus graft survivals were 61%, 52%, and 52% versus 61%, 52%, and 52% in
      contrast with primary OLT rates of 81%, 75%, and 70% versus 79%, 72%, and 61%
      respectively at (P = .03). In conclusion, our data suggested that the
      characteristics and number of early reOLTs did not change over time. However, the
      rate of late reOLTs increased. This can be explained by the increased rate of
      late onset biliary complications in spite of proper interventional radiological
      treatment. The second conclusion is that hepatitis C virus (HCV) recurrence did
      not become a main indication among late reOLT. Since a center policy states that
      patients with an early, cholestatic HCV recurrence are not referred for a
      secondary transplantation.

PMID- 24314999
TI  - Technical risk factors for hepatic artery thrombosis after orthotopic liver
      transplantation: the Hungarian experience.
AB  - Hepatic artery thrombosis (HAT) significantly affects graft loss and mortality
      after orthotopic liver transplantation (OLT). The aim of this study was to
      analyze the risk factors of HAT in our program, with special regard to the
      personal-technical factor. We retrospectively analyzed the data of 500 adult
      liver transplant recipients between 1995 and 2011. Operations were performed by a
      certain group of surgeons, with standardized technique. The incidence rate of HAT
      decreased since 1995 from 12% to 7.8%. In accordance with the literature, HAT
      associated with acute rejection, polytransfusion, and the duration of the
      hepatectomy, arterial variations/reconstructions, tiny arteries, and furthermore,
      the timing of the anastomosis in Hungary. However we did not find an association
      with other parameters, like cytomegalovirus infection, and hepatocellular
      carcinoma as indication. We created a "difficulty index" that consists of the
      technical parameters. The difficulty index together with surgical experience
      (number of OLTs performed) had an outstanding association with HAT. In
      conclusion, the incidence and risk factors for HAT are similar to the results
      published by others. However, personal factors, such as experience, timing, given
      anatomy, and tiredness, might also play a significant role in the occurrence of
      HAT.

PMID- 24315000
TI  - Biliary complications after orthotopic liver transplantation: the Hungarian
      experience.
AB  - Biliary complications (BC) significantly affect morbidity and mortality after
      orthotopic liver transplantation (OLT). The aim of this study was to analyze the
      incidence and types of biliary complications after OLT in Hungary. We
      retrospectively analyzed data of 471 adult liver transplant recipients between
      1995 and 2011. Biliary complications occurred in 28% of patients. The most
      frequent BCs were bile duct stricture, stenosis (19%), biliary leakage (12%), and
      necrosis (BN: 6.4%). Biliary complications were associated with the incidence of
      acute rejection (51% vs 31%; P = .003), hepatic artery thrombosis (43% vs 11%; P
      < .001), and hepatic artery stenosis (26% vs 11%; P = .002). When cold ischemic
      time was longer than 12 hours, leakage (10% vs 3%; P = .043), ischemic type
      biliary lesion (20% vs 3.4%; P = .05), and BN (12% vs 3%; P = .067) were more
      often diagnosed post-OLT. Most of the biliary complications were treated by
      radiologic interventions (70%). Bile duct necrosis was associated with lower
      graft and patient survival. In conclusion, acute rejection, hepatic artery
      thrombosis/stenosis and cold ischemic time longer than 12 hours increase the
      incidence of BCs. Successful management of these risk factors can reduce the
      incidence of biliary complications and improve mortality.

PMID- 24315001
TI  - Examination of carbohydrate metabolism parameters after simultaneous pancreas
      kidney transplantation.
AB  - End-stage renal failure, a frequent complication of type 1 diabetes mellitus,
      requires renal replacement therapy. Our team examined the laboratory parameters
      of carbohydrate metabolism in 18 patients with type 1 diabetes at 10 to 89 months
      after simultaneous pancreas-kidney transplantation. We compared these results
      with those of 17 patients with type 1 diabetes who had formerly received kidney
      alone transplantations, and were undergoing insulin treatment, as well as with
      those of 16 metabolically healthy controls. The hemoglobin A1c (HbA1c) and blood
      glucose levels of the pancreas-kidney transplant recipients were within the
      normal ranges, not differing significantly from those of the healthy controls. In
      contrast, the HbA1c and glucose levels were significantly elevated among kidney
      transplanted diabetic subjects. However, fasting and 2-hour insulin levels of
      pancreas-kidney transplant patients were significantly higher than those of the
      controls, indicating insulin resistance. According to these results, the insulin
      secretion by the pancreas graft sufficiently compensated for insulin resistance.
      Thus 10 to 89 months after successful pancreas-kidney transplantation,
      carbohydrate metabolism by type 1 diabetic patients was well controlled without
      antidiabetic therapy. 

PMID- 24315002
TI  - Kidney transplantation in hereditary coproporphyria using tacrolimus and
      mycophenolate mofetil: a case report.
AB  - BACKGROUND: The porphyrias are a group of disorders of the heme biosynthesis
      pathway that may present with acute life-threatening attacks, commonly
      exacerbated by a wide variety of medications. Many newer immunosuppressive
      medications, which are in use following kidney transplantation, have not been
      fully explored in acute porphyrias. CASE REPORT: A 53-year-old woman received a
      kidney from a deceased donor, after being on hemodialysis for 4 years. Hereditary
      coproporphyria was diagnosed at age 19 years. We administered tacrolimus,
      mycophenolate mofetil and steroid immunosuppression. In the immediate post
      transplant periods she displayed abdominal pain and transient uroporphyrin
      elevation in parallel with slightly elevated (15 ng/mL) tacrolimus
      concentrations. As the target tacrolimus level was achieved, these findings
      disappeared. CONCLUSIONS: Tacrolimus, mycophenolate- mofetil, and steroid therapy
      for hereditery coproporphyri was safe, in the long term.

PMID- 24315003
TI  - Successful treatment of renal failure caused by multiple myeloma with HLA
      identical living kidney and bone marrow transplantation: a case report.
AB  - Here we have described a successful HLA-identical living allogeneic kidney
      transplantation after bone marrow transplantation in a patient with end-stag
      liver disease caused by multiple myeloma (MM). Our case is unique, because this
      combined transplantation is rarely possible and because of our unique
      immunosuppressive and management strategies. A 45-year-old man with ESRD MM and
      kappa light-chain nephropathy was diagnosed. Cytostatic treatment resulted in
      partial remission, so autologous peripheral stem cell transplantation (SCT) was
      performed leading to a complete remission; however the patient remained anuric.
      The patient's HLA-identical brother offered to be a donor of peripheral stem
      cells for collection and cryopreservation. Kidney transplantation was performed
      with a combination of tacrolimus sirolimuns, and methylprednisolone. With a well
      functioning kidney graft, allogeneic SCT was performed in the incipient relapse
      phase of MM, after total body irradiation. Severe oropharyngeal infections,
      diarrhea, sepsis, and renal failure. Fearing acute renal rejection, we
      administered steroid bolus. He experienced therapy with gradual restoration of
      kidney function. Then, steroid-responsive acute graft-versus-host disease (grade
      II, predominantly bowel) was diagnosed on the background of diarrhea, which
      returned once. Later he experienced a left subclavian vein thrombosis at the site
      of a central venous catheter and sepsis. Having recovered from these events, the
      patient enjoys good health, with stable kidney function and normal protein
      excretion. After the steroid was stopped, a bone marrow biopsy revealed full
      donor type normocellular hemopoiesis. Because of the chimerism, we gradually
      discontinued the immunosuppression including, sirolimus and finally tacrolimus,
      since with minimal trough levels there were no complications. Bone marrow biopsy
      showed a complete remission. In MM with ESRD HLA-identical combined kidney and
      bone marrow transplantation from a living donor may offer not only complete
      remission and good renal function, but also good health without
      immunosuppression.

PMID- 24315005
TI  - Cost-effectiveness of policies aimed at increasing organ donation: the case of
      Chile.
AB  - BACKGROUND: In this article we present an economic evaluation of policies aimed
      at increasing deceased organ donation in Chile, a developing country that has low
      donation rates; it had 5.4 donors per million people (pmp) in 2010. METHODS:
      Expert opinions of leading participants in donation and transplantation were
      analyzed, resulting in a set of local policies aimed at increasing donation
      rates. Using previous results of reported cost savings of increasing kidney
      transplantation in Chile, we estimated the net benefits of these policies, as a
      function of additional donors. RESULTS: The main problem of the Chilean system
      seems to be the low capability to identify potential donors and a deficit in
      intensive care unit (ICU) beds. Among considered policies central to increase
      donation are the following: increasing human and capital resources dedicated to
      identifying potential donors, providing ICU beds from private centers, and
      developing an online information system that facilitates procurement coordination
      and the evaluation of performance at each hospital. Our results show that there
      is a linear relationship between cost savings and incremental donors pmp. For
      example, if these policies are capable of elevating donation rates in Chile by 6
      donors pmp net estimated cost savings are approximately US $1.9 million.
      Likewise, considering the effect on patients' quality of life, savings would
      amount to around $15.0 million dollars per year. CONCLUSIONS: Our estimates
      suggest that these policies have a large cost-saving potential. In fact,
      considering implementation costs, cost reduction is positive after 4 additional
      donors pmp, and increasing afterward.

PMID- 24315006
TI  - Results in laparoscopic living donor nephrectomy: a multicentric experience.
AB  - OBJECTIVE: Renal transplantation is the most successful therapy to improve
      survival and quality of life for patients with end-stage renal disease. Living
      donors have been used as an alternative to reduce the stay on the waiting list.
      Laparoscopic living donor nephrectomy has become the standard procedure for renal
      transplantation. Minimally invasive surgery involves less postoperative pain with
      less analgesic requirements allowing shorter hospital stay for the donor.
      MATERIAL AND METHODS: We retrospectively analyzed demographic and intraoperative
      data and surgical complications for 46 patients who underwent laparoscopic living
      donor nephrectomy between March 2001 and March 2011. RESULTS: Mean donor age was
      41 years. Mean operative time was 170 +/- 45 minutes. The average cold ischemic
      time was 40 minutes and warm ischemic time was 26 minutes. Twenty-one patients
      were donors for pediatric receptors. Fourty patients underwent left laparoscopic
      nephrectomy, the other 6 patients underwent right laparoscopic nephrectomy due to
      vascular anatomic variant. Right laparoscopic nephrectomy was converted in 1 case
      (2.2%) due to renal vein laceration without donor morbidity and without
      compromise of graft function. Renal function at the second day post donor
      nephrectomy was measured using serum creatinine averaged 1.2 mg/dL with a mean
      increase of 0.4 mg/dL from baseline, with normalization after 30 days. No patient
      required blood transfusion, and there were no immediate surgical complications,
      infections, or mortality. One patient developed an incisional hernia in relation
      to the site of kidney removal. The mean hospital stay was 5 +/- 1 days.
      CONCLUSIONS: Laparoscopic nephrectomy in our experience is a safe technique
      without postoperative morbidity or mortality. It is associated with low levels of
      pain, early discharge and early return to physical activity and work, good sense
      of aesthetic results, and long-term graft function comparable to traditional
      nephrectomy and cadaveric grafts.

PMID- 24315007
TI  - Urinary exosomes as a source of kidney dysfunction biomarker in renal
      transplantation.
AB  - End-stage renal disease (ESRD) requires for its treatment permanent dialysis or
      kidney transplantation (KT). KT is the best clinical treatment, however, the
      early function of the allograft varies depending on multiple factors associated
      with cold ischemia time (CIT) and the allograft rejection process. It is known
      that serum creatinine is an insensitive and late marker for predicting graft
      recovery after KT, mainly in patients with delayed graft function (DGF).
      Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the distal
      nephron and it is one of the most promising novel biomarkers for acute kidney
      injury (AKI) and chronic kidney disease (CKD). NGAL has been proposed to be a
      predictor of organ recovery from DGF after KT from donors after cardiac death.
      Because nonrenal diseases can also induce NGAL, more information is necessary to
      validate the sensitivity and specificity of urine and plasma NGAL in clinical
      samples. The exosomes are vesicles released into the urine from the kidney
      epithelium and they have been proposed as better source to explore as biomarker
      of renal dysfunction. The molecular composition of the urinary exosomes could be
      representative of the physiological or physiopathologic condition of the urinary
      system. We propose that determination of NGAL in urinary exosomes is a better
      predictor of kidney dysfunction after KT than other urinary fractions. We
      analyzed 15 kidney allograft recipients, with a mean age of 36 years (range, 16
      60 years) and 75% were male: 11 living donors (LD) and 4 deceased donors (DD).
      The average length of CIT was 14 hours in DD and less than 1 hour in LD. Three
      patient developed DGF. Using Western blot analysis, NGAL was detectable in the
      cellular and exosomal fraction of the urine. The exosomes expressed higher levels
      of NGAL than the cellular fraction. The expression of NGAL was observed from the
      first day after transplantation. In the cellular fraction of the urine, no
      significant differences of NGAL were observed between the patients. However, the
      median of NGAL expression in the exosomes fraction was significantly higher in DD
      patient, from the first day after KT (P < .05). Moreover, we noticed that NGAL
      expression in exosomes remained elevated in the patients with DGF compared with
      non-DGF patients (P < .05). Considering the highest abundance of NGAL in the
      urinary exosomes and its correlation with DGF patients, we suggest the exosomal
      fraction as a more sensitive substrate to evaluate early biomarkers of DGF after
      KT.

PMID- 24315008
TI  - Pediatric liver transplantation experience and outcome in Chile.
AB  - INTRODUCTION: In 1994 our group began its experience with pediatric liver
      transplantation. The experience gained during this period is the largest in the
      country, positioning the Hospital Luis Calvo Mackenna and Clinica Las Condes as
      major referral centers in the public and private sectors. The aim of this study
      was to report our experience of our pediatric liver transplantation program
      during this period. METHODS: The liver transplantation database of Hospital Luis
      Calvo Mackenna and Clinica Las Condes between January 1994 and July 2011 was
      reviewed recording age, gender, indications for transplantation, surgical
      technique, complications, and survival. Survival rates were calculated using
      Kaplan-Meier analysis. RESULTS: During the period described 230 transplantations
      were performed in 189 pediatric patients. Fifty-five percent were male patients.
      The average age was 5 years. The main causes of transplantation were biliary
      atresia (50%), fulminant hepatic failure (25%), and other cholestatic diseases by
      10%. Vascular and biliary complications were the leading cause of graft loss and
      retransplantation. The overall rate of retransplantation at 5 years was 20%. The
      technique of living donor was used in 28% of the cases. The 1-year patient
      actuarial survival rate was 80%, 73% at 5 years, and 68% at 10 years. In the last
      3 years the survival rate at 1 year exceeds 90%. DISCUSSION: Our program includes
      more than 90% of the national liver experience. The incorporation of living donor
      is a milestone that has enabled us to save many patients who previously died
      while waiting for an organ. Its use in cases of full acute liver failure has
      allowed us to dramatically reduce mortality on the waiting list. Our results in
      the last 3 years reflect the experience that results in a significant decrease in
      mortality, comparing favorably to other series published in the international
      literature.

PMID- 24315009
TI  - Pediatric liver transplant outcome using severe hypernatremic donors.
AB  - INTRODUCTION: Pediatric liver transplantation is limited by donation. In the last
      5 years, urgent conditions have forced transplant teams to accept donors with
      minor suboptimal conditions, termed "extended donor criteria." Among those, the
      risk of using severe hypernatremic donors (SHD) for liver transplant is not yet
      well established. The aim of this study is to report the outcome of pediatric
      patients receiving grafts from SHD. METHODS: Clinical records of patients
      transplanted in the last 3 years at Hospital Luis Calvo Mackenna, Santiago,
      Chile, were reviewed. Outcome was evaluated in terms of patient and graft
      survival and complications potentially associated to the donor condition.
      RESULTS: Five of 33 deceased donor transplants presented with SHD. All recipients
      were waiting transplant in an acute condition, one of them in acute liver failure
      (ALF). No living related donor was available. Donors' serum sodium was 169 to 193
      mEq/L before medical management and between 157 and 172 mEq/L at procurement. One
      patient died from sepsis related to biliary complications, and the patient
      suffering ALF developed primary graft nonfunction, received a second transplant 2
      weeks later, and recovered to stable medical condition. No other complication was
      registered in these patients. DISCUSSION: Our findings allow us to postulate that
      hypernatremic deceased donors may be used for pediatric liver transplant under
      special circumstances.

PMID- 24315010
TI  - Health-related quality of life after pediatric liver transplant: single-center
      experience in Chile.
AB  - INTRODUCTION: Orthotopic liver transplantation is the treatment of choice for
      most terminal liver diseases in children. Currently, the improved survival of
      these patients is well documented, but their quality of life post-transplant is
      not described. In Chile, Hospital Luis Calvo Mackenna (HLCM) has performed
      pediatric liver transplantation in children from around the country since 1994.
      The aim of this study is to evaluate our patients' and parents' current quality
      of life. METHODS: A cross-sectional study was conducted between July 2010 and
      June 2011. All liver transplant patients currently in control at HLCM were
      invited to complete the PedsQL 4.0 report (Pediatric Quality of Life Inventory).
      For each group, average score was calculated and comparisons were done using
      Student t and chi(2) tests. RESULTS: Forty-nine patients were enrolled. One-third
      of the patients were between 2 and 4 years, one-third between 5 and 12, and the
      rest were 13 to 18 years old. Half of the patients had their transplants for more
      than 3 years, 53% were female, 53% lived in cities far from the transplant
      center, 72.5% had chronic liver disease, 53% had received a liver from cadaveric
      donor, and 21% had received more than 1 liver transplant. Patients under 4 years
      referred good health-related quality of life (HRQOL) in all categories. All
      school-age patients had poor or very poor psychosocial HRQOL. DISCUSSION: Our
      good results obtained in transplant patients under 4 years may be because the
      questionnaire was completed by caregivers. The school-age patients were affected
      in terms of school functioning, as they were not able to participate in all the
      activities. These findings need to be compared with HRQOL perception in other
      groups, such as children with other chronic conditions, and evaluated with other
      broader factors, as reported in international HRQOL publications.

PMID- 24315011
TI  - Liver transplantation in children weighing less than 10 kg: Chilean experience.
AB  - BACKGROUND: Orthotopic liver transplantation is the treatment of choice for most
      terminal liver diseases in children. In small children (<= 10 kg), this procedure
      is challenging and has special considerations. The aim of this study is to
      describe the experience of a Chilean liver transplantation program in this
      subgroup of patients. METHODS: The liver transplant database of Hospital Luis
      Calvo Mackenna and Clinica Las Condes was reviewed. All children less than 10 kg
      undergoing liver transplantation between January 1994 and July 2011 were
      included. Patient and graft outcomes and main complications were analyzed.
      RESULTS: We have performed 230 pediatric liver transplantations, 49 of them in 41
      patients weighing less than 10 kg. The first indication for transplantation was
      biliary atresia in 25 patients (61%). A living related donor was used in 23 cases
      (51%). Actuarial survival was 75.7% at 1 year and 67.1% at 5 years. The main
      cause of death was infection, and the leading cause of graft loss was vascular
      complication. DISCUSSION: Our transplant program includes 2 centers that perform
      more than 90% of pediatric liver transplantations in Chile, including public
      health pediatric patients from all around the country. Patients weighing less
      than 10 kg represent the most challenging group in pediatric liver
      transplantation due to higher rates of vascular and biliary complications and
      postoperative infections.

PMID- 24315012
TI  - Umbilical cord blood transplantation in hematologic diseases in patients over 15
      years old: long-term experience at the Pontificia Universidad Catolica de Chile.
AB  - Most patients who require a sibling stem cell transplantation do not have a
      matched donor. In our experience, only 1/3 patients have a matched unrelated
      donor (MUD); therefore, the majority of the patients will require umbilical cord
      blood (UCB). Patients treated for hematologic diseases with UCB transplants were
      included. UCB selection and conditioning regimens were performed according to the
      Minnesota group. Graft-versus-host disease (GVHD) prophylaxis, infection
      prevention, and patient care were performed according to institutional
      guidelines. We analyzed patients and graft demography, neutrophil and platelet
      recovery, chimerism kinetics, GVHD incidence, overall (OS), progression-free
      survival (PFS) and transplant-related mortality (TRM). We included 29 patients
      with a median age of 34.8 years (range 15-55). Eighteen were male and the median
      weight was 72.6 kg (range 54-100). Nineteen patients had acute leukemia.
      Myeloablative (MA) conditioning was used in 27 patients. Seventeen received
      double UCB (DUCB) grafts. Median total nucleated cell (10(7)/kg) was 4.2 (range
      3.9-4.9) and 4.4 (range 2.8-6.3) for single UCB (SUCB) and DUCB transplants,
      respectively. Median time for neutrophil engraftment was 24.7 (range 14-43) and
      25.8 days (range 14-52) after SUCB and DUCB transplants, respectively. Median
      time for platelet engraftment was 147 (range 30-516) and 81 days (range 37-200)
      after SUCB and DUCB transplants, respectively. All the patients receiving MA
      conditioning had >95% chimerism shortly after transplant. Cumulative incidence of
      grades II-IV and III-IV acute GVHD was 41% and 20%, respectively. Localized
      chronic GVHD was seen in 14% of the patients. Median follow-up was 16.7 months
      (range 1-63). Five-year OS and PFS were 38% and 39%, respectively. One-year TRM
      was 42%. UCB transplantation is associated with potential cure of hematologic
      malignancies and our results are similar to other series. Studies are needed to
      decrease mortality and improve immune reconstitution.

PMID- 24315013
TI  - Effect of exenatide therapy on hepatic fat quantity and hepatic biomarkers in
      type 2 diabetic patients.

PMID- 24315014
TI  - XRCC3 Thr241Met polymorphism and gastric cancer susceptibility: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: X-ray repair cross-complementing group 3 (XRCC3) is
      responsible for maintaining the integrity of the genome, playing a critical role
      in protecting it against mutations which lead to cancer. Polymorphisms at exons 7
      of the XRCC3 gene may alter the XRCC3 repair efficiency. The aim of this study is
      to derive a precise estimation of the relationship between XRCC3 Thr241Met
      polymorphism and gastric cancer (GC) risk. METHODS: Two investigators
      independently searched the databases of Pubmed, EMBASE and China National
      Knowledge Infrastructure (CNKI) up to May 15, 2013. Odds ratio (OR) and 95%
      confidence intervals (CI) for XRCC3 Thr241Met polymorphism and GC were calculated
      in a fixed- or random- effects model depending on statistical heterogeneity.
      RESULTS: This meta-analysis included 9 case-control studies, which included 2209
      cases and 3269 controls. Overall, the combined results based on all studies
      indicated that there was no association between XRCC3 Thr241Met polymorphism and
      GC susceptibility for all genetic models. When stratifying for race, we found the
      241Met/Met genotype carriers might be at high risk of GC among Asians, but not
      among Caucasians. When stratifying by the location of gastric cancer, the
      combined results showed that Met/Met genotype carriers might have an increased
      risk of GC in non-cardiac gastric cancer, but not in cardiac cancer. CONCLUSION:
      This meta-analysis confirmed that the XRCC3 Thr241Met gene polymorphism might be
      a risk factor for GC among Asians, and that differences in genotype distribution
      may be related to the location of gastric cancer. More well-designed studies
      based on larger population are needed to confirm our results.

PMID- 24315015
TI  - Nonlinear dynamics of confined liquid systems with interfaces subject to forced
      vibrations.
AB  - A review is presented of the dynamic behavior of confined fluid systems with
      interfaces under monochromatic mechanical forcing, emphasizing the associated
      spatio-temporal structure of the fluid response. At low viscosity, vibrations
      significantly affect dynamics and always produce viscous mean flows, which are
      coupled to the primary oscillating flow and evolve on a very slow timescale.
      Thus, unlike the primary oscillating flow, mean flows may easily interact with
      the surface rheology, which generates dynamics that usually exhibit a much slower
      timescale than that of typical gravity-capillary waves. The review is made with
      an eye to the typical experimental devices used to measure surface properties,
      which usually consist of periodically forced, symmetric fluid systems with
      interfaces. The current theoretical description of these systems ignores the
      fluid mechanics, which could play a larger role than presently assumed. 

PMID- 24315016
TI  - Evaluation of the 23S rRNA gene as target for qPCR based quantification of
      Frankia in soils.
AB  - The 23S rRNA gene was evaluated as target for the development of Sybr Green-based
      quantitative PCR (qPCR) for the analysis of nitrogen-fixing members of the genus
      Frankia or subgroups of these in soil. A qPCR with a primer combination targeting
      all nitrogen-fixing frankiae (clusters 1, 2 and 3) resulted in numbers similar to
      those obtained with a previously developed qPCR using nifH gene sequences, both
      with respect to introduced and indigenous Frankia populations. Primer
      combinations more specifically targeting three subgroups of the Alnus host
      infection group (cluster 1) or members of the Elaeagnus host infection group
      (cluster 3) were specific for introduced strains of the target group, with
      numbers corresponding to those obtained by quantification of nitrogen-fixing
      frankiae with both the 23S rRNA and nifH genes as target. Method verification on
      indigenous Frankia populations in soils, i.e. in depth profiles from four sites
      at an Alnus glutinosa stand, revealed declining numbers in the depth profiles,
      with similar abundance of all nitrogen-fixing frankiae independent of 23S rRNA or
      nifH gene targets, and corresponding numbers of one group of frankiae of the
      Alnus host infection only, with no detections of frankiae representing the
      Elaeagnus, Casuarina, or a second subgroup of the Alnus host infection groups. 

PMID- 24315017
TI  - Localization of the epileptogenic tuber with electric source imaging in patients
      with tuberous sclerosis.
AB  - PURPOSE: Patients with tuberous sclerosis complex (TSC) often suffer from
      medically refractory epilepsy. Despite the multifocality of the disease,
      resection of the most epileptogenic tuber can lead to major improvement of
      seizure control. Therefore, non-invasive imaging methods are needed for detecting
      epileptogenic sources. We assessed the utility of electric source imaging (ESI)
      in the presurgical work-up of TSC patients and its combination with Positron
      Emission Tomography (PET) and ictal/interictal Single Photon Emission Computed
      Tomography (SISCOM). METHODS: Thirteen patients underwent high density ESI (8/13)
      and/or low density ESI (13/13). We investigated the concordance between ESI, PET,
      SISCOM and the resection area in the 11 operated patients (nine seizure-free).
      RESULTS: High resolution ESI was partially or completely concordant with the
      resected area in 5/5 seizure free patients. Low resolution ESI was partially or
      completely concordant in 7/9 seizure free patients. PET and SPECT were concordant
      (partially or completely) in 8/9 and 6/9 cases, respectively. We found multifocal
      ESI sources in 2/9 seizure free patients, marked multifocal PET hypometabolism in
      3/9 and multifocal SISCOM in 4/9. The region of concordant ESI and PET accurately
      predicted the dominant epileptogenic source in 6/9 patients. The same was true
      for concordant ESI and SISCOM in 4/9 patients, whereas the coregistration of only
      PET and SISCOM was insufficient in 3/9 successfully operated cases. The
      combination of all three imaging modalities could successfully identify the
      resection area in all but one patient with a favorable post-operation outcome.
      CONCLUSION: ESI is an important tool for the pre-surgical evaluation of TSC
      patients. It complements PET and SPECT results and can improve the management of
      candidates for surgery when integrated with electro-clinical information.

PMID- 24315018
TI  - Advanced diffusion imaging sequences could aid assessing patients with focal
      cortical dysplasia and epilepsy.
AB  - Malformations of cortical development (MCD), particularly focal cortical
      dysplasia (FCD), are a common cause of refractory epilepsy but are often
      invisible on structural imaging. NODDI (neurite orientation dispersion and
      density imaging) is an advanced diffusion imaging technique that provides
      additional information on tissue microstructure, including intracellular volume
      fraction (ICVF), a marker of neurite density. We applied this technique in 5
      patients with suspected dysplasia to show that the additional parameters are
      compatible with the underlying disrupted tissue microstructure and could assist
      in the identification of the affected area. The consistent finding was reduced
      ICVF in the area of dysplasia. In one patient, an area of reduced ICVF and
      increased fibre dispersion was identified that was not originally seen on the
      structural imaging. The focal reduction in ICVF on imaging is compatible with
      previous iontophoretic data in surgical specimens, was more conspicuous than on
      other clinical or diffusion images (supported by an increased contrast-to-noise
      ratio) and more localised than on previous DTI studies. NODDI may therefore
      assist the clinical identification and localisation of FCD in patients with
      epilepsy. Future studies will assess this technique in a larger cohort including
      MRI negative patients. 

PMID- 24315019
TI  - Clinical value of magnetoencephalographic spike propagation represented by
      spatiotemporal source analysis: correlation with surgical outcome.
AB  - OBJECTIVE: To investigate the correlation between spike propagation represented
      by spatiotemporal source analysis of magnetoencephalographic (MEG) spikes and
      surgical outcome in patients with temporal lobe epilepsy. METHODS: Thirty-seven
      patients were divided into mesial (n=27) and non-mesial (n=10) groups based on
      the presurgical evaluation. In each patient, ten ipsilateral spikes were
      averaged, and spatiotemporal source maps of the averaged spike were obtained by
      using minimum norm estimate. Regions of interest (ROIs) were created including
      temporoparietal, inferior frontal, mesial temporal, anterior and posterior part
      of the lateral temporal cortex. We extracted activation values from the source
      maps and the threshold was set at half of the maximum activation at the peak
      latency. The leading and propagated areas of the spike were defined as those ROIs
      with activation reaching the threshold at the earliest and at the peak latencies,
      respectively. Surgical outcome was assessed based on Engel's classification.
      Binary variables were created from leading areas (restricted to the anterior and
      mesial temporal ROIs or not) and from propagation areas (involving the
      temporoparietal ROI or not), and for surgical outcome (Class I or not). Fisher's
      exact test was used for significance testing. RESULTS: In total and mesial group,
      restricted anterior/mesial temporal leading areas were correlated with Class I
      (p<0.05). Temporoparietal propagation was correlated with Class II-IV (p<0.05).
      For the non-mesial group, no significant relation was found. CONCLUSIONS: Spike
      propagation patterns represented by spatiotemporal source analysis of MEG spikes
      may provide useful information for prognostic implication in presurgical
      evaluation of epilepsy.

PMID- 24315020
TI  - Suggestive linkage of familial mesial temporal lobe epilepsy to chromosome 3q26.
AB  - PURPOSE: To describe the clinical findings in a family with a benign form of
      mesial temporal lobe epilepsy and to identify the causative genetic factors.
      METHODS: All participants were personally interviewed and underwent neurologic
      examination. The affected subjects underwent EEG and most of them
      neuroradiological examinations (MRI). All family members were genotyped with the
      HumanCytoSNP-12 v1.0 beadchip and linkage analysis was performed with Merlin and
      Simwalk2 programs. Exome sequencing was performed on HiSeq2000, after exome
      capture with SureSelect 50 Mb kit v2.0. RESULTS: The family had 6 members with
      temporal lobe epilepsy. Age at seizure onset ranged from 8 to 13 years. Five
      patients had epigastric auras often associated to oro-alimentary automatic
      activity, 3 patients presented loss of contact, and 2 experienced secondary
      generalizations. Febrile seizures occurred in 2 family members, 1 of whom also
      had temporal lobe epilepsy. EEG showed focal slow waves and epileptic
      abnormalities on temporal regions in 1 patient and was normal in the other
      affected individuals. MRI was normal in all temporal lobe epilepsy patients. We
      performed single nucleotide polymorphism-array linkage analysis of the family and
      found suggestive evidence of linkage (LOD score=2.106) to a region on chromosome
      3q26. Haplotype reconstruction supported the linkage data and showed that the
      majority of unaffected family members carried the haplotype at risk. Whole exome
      sequencing failed to identify pathogenic mutations in genes of the candidate
      region. CONCLUSIONS: Our data suggest the existence of a novel locus for benign
      familial mesial temporal lobe epilepsy on chromosome 3q26. Our failure to
      identify pathogenic mutations in genes of this region may be due to limitations
      of the exome sequencing technology.

PMID- 24315021
TI  - Parkinson's disease: less epileptic seizures, more status epilepticus.
AB  - We compared the rate of epilepsy and status epilepticus (SE) in patients with and
      without Parkinson's disease (PD). Out of 1215 patients with idiopathic PD, 31 had
      epilepsy and 19 of these had at least one episode of SE (61.3%) compared to 298
      of 2537 patients (11.7%; p<0.001) with epilepsy and without concomitant PD. This
      clinical finding supports the hypothesis that the functional impairment of the
      basal ganglia in PD patients makes SE more likely. 

PMID- 24315022
TI  - Autosomal dominant lateral temporal epilepsy (ADLTE): absence of chromosomal
      rearrangements in LGI1 gene.
AB  - Mutations of leucine-rich, glioma inactivated 1 (LGI1) gene are found in about
      half of the families with autosomal dominant lateral temporal epilepsy (ADLTE).
      More recently a LGI1 heterozygous microdeletion was found in a single ADLTE
      family, suggesting that submicroscopic chromosomal abnormalities should be
      investigated in cases negative for LGI1 mutations. This study examines whether
      microdeletions and duplications of the LG1 gene occurred in eight ADLTE families
      and 20 sporadic patients that were negative for LGI1 mutations. Multiplex
      ligation-dependent probe amplification (MLPA) was applied to detect potential
      deletions and duplications of LGI1 gene. In all patients, MLPA analysis did not
      reveal any pathogenic changes in the LGI1 gene. Chromosomal rearrangements
      involving the LGI1 gene were not identified in our series of familial or sporadic
      LTE. These results further illustrate the considerable genetic heterogeneity for
      ADLTE, despite the relatively homogeneous clinical picture. There are as yet
      undiscovered mechanisms underlying ADLTE. 

PMID- 24315023
TI  - Causal influence of epileptic network during spike-and-wave discharge in juvenile
      myoclonic epilepsy.
AB  - Electroencephalographic (EEG) characteristic of juvenile myoclonic epilepsy (JME)
      is spike-and-wave discharge (SWD), which is dominant in the frontal region.
      However, activity in the parietal area, including the precuneus, has also been
      documented for several seconds before and during SWD. The aim of this study was
      to identify the role of the parietal region, especially the precuneus, and to
      clarify the causal dynamics among cortical regions during SWD. EEGs were obtained
      from seven patients with JME. Each SWD was divided into six distinct temporal
      phases: spike onset, spike peak, slow-wave onset, slow-wave ascending, slow-wave
      peak, and slow-wave descending phases. Based on the cortical current source
      distribution and the results of a previous study, we selected the medial frontal,
      orbitofrontal, anterior cingulate, and mesial temporal cortices and the precuneus
      as regions of interest (ROIs). To assess epileptic networks and the causal
      relationships among ROIs during SWD, the directed transfer function (DTF), a
      measure of multivariate causality, was calculated for each phase of SWD. During
      spike onset, the maximal outdegree region in all patients was the precuneus. The
      spike-peak and slow-wave onset phases did not show a consistently dominant
      outflow region. Outflow from the anterior cingulate cortex was dominant in four
      patients during the slow-wave ascending phase, and the precuneus showed the
      maximal outdegree in six patients during the slow-wave peak. In the slow-wave
      descending phase, four patients showed maximal outflow from the temporal cortex.
      Our findings suggest that the precuneus is likely a key region for SWD despite
      the small amount of neural activity observed. The precuneus was the region with
      the maximal outdegree during both the spike onset and slow-wave peak phases,
      indicating that SWD in JME is initiated and sustained by a network involving the
      frontal cortex, precuneus, and thalamus. 

PMID- 24315024
TI  - Lack of pathogenic mutations in six patients with MMPSI.
AB  - Sequencing of the KCNT1, PLCB1, SCN1A and TBC1D24 loci was performed in six
      children with typical features of malignant migrating partial seizures of infancy
      (MMPSI), to verify the presence of potential disease-causing mutations, including
      those already reported to be associated with the disease. Sanger sequencing
      failed to identify in these genes the previously reported pathogenic mutations in
      these patients, while a comprehensive mutational scanning analysis of these four
      loci by targeted re-sequencing led to detection of both intronic and exonic new
      variants. Based on the current knowledge, the sequence variants identified here
      do not allow to predict functional phenotypes that might explain, at least in
      part, MMPSI symptoms. 

PMID- 24315025
TI  - Ozonation of wastewater: removal and transformation products of drugs of abuse.
AB  - In this study amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA),
      cocaine (COC), benzoylecgonine (BE), ketamine (KET) and oxycodone (OXY) in
      wastewater at concentrations of 100 MUgL(-1) were subjected to ozone to determine
      their removals as a function of ozone dose and to identify significant oxidation
      transformation products (OTPs) produced as a result of ozonation. A method based
      on high resolution mass spectrometry and differential analysis was used to
      facilitate and accelerate the identification and structural elucidation of the
      transformation products. The drug removal ranged from 3 to 50% depending on the
      complexity of the matrix and whether a mixture or individual drugs were ozonated.
      Both transient and persistent oxidation transformation products were identified
      for MDMA, COC and OXY and their chemical formulae were determined. Three possible
      structures of the persistent transformation product of MDMA (OTP-213) with
      chemical formula C10H16O4N, were determined based on MS(n) mass spectra and the
      most plausible structure (OTP-213a) was determined based on the chemistry of
      ozone. These results indicate that ozone is capable of removing drugs of abuse
      from wastewater to varying extents and that persistent transformation products
      are produced as a result of treatment.

PMID- 24315026
TI  - Quantification of emissions from domestic heating in residential areas of Izmir,
      Turkey and assessment of the impact on local/regional air-quality.
AB  - Air pollution in cities is a major environmental problem principally in the
      developing countries. The quantification of emissions is a basic requirement to
      assess the human influence to the atmosphere. The air quality generally shows
      decreases with the major contribution residential emissions and meteorology in
      the winter season in the big cities. Poor meteorological conditions especially
      inversion events for the efficient mixing of air pollutants occurred during the
      winter months in Izmir. With this work we quantify the amount of domestic heating
      emissions for particulate matter (PM10), sulfur dioxides (SO2), nitrogen dioxides
      (NO2), volatile organic compounds (VOC) and carbon monoxide (CO) together with
      greenhouse gases which are carbon dioxide (CO2), nitrous oxide (N2O) and methane
      (CH4) in Izmir for 2008-2009 winter season. The results showed that the most
      affected residential areas were central districts in the city center from
      domestic heating emissions due to meteorological condition and demographic
      reasons. Air quality modeling is a great tool for assisting policy makers how to
      decrease emissions and improve air quality. At the second part of the study,
      calculated emissions were modeled by using CALMET/CALPUFF dispersion modeling
      system and plotted in the form of air pollution maps by using geographical
      information system to determine the locations and estimate the effects of the new
      residential areas that will be established in the future in Izmir. 

PMID- 24315027
TI  - Effect of EDTA washing of metal polluted garden soils. Part I: Toxicity hazards
      and impact on soil properties.
AB  - We applied a multi-level approach assessing the quality, toxicity and functioning
      of Pb, Zn and Cd contaminated/remediated soil from a vegetable garden in Meza
      Valley, Slovenia. Contaminated soil was extracted with EDTA and placed into field
      experimental plots equipped with lysimeters. Soil properties were assessed by
      standard pedological analysis. Fractionation and leachability of toxic metals
      were analyzed by sequential extraction and TCLP and metal bioaccessibility by UBM
      tests. Soil respiration and enzyme activities were measured as indicators of soil
      functioning. Remediation reduced the metal burden by 80, 28 and 72% for Pb, Zn
      and Cd respectively, with a limited impact on soil pedology. Toxic metals
      associated with labile soil fractions were largely removed. No shifts between
      labile and residual fractions were observed during the seven months of the
      experiment. Initial metal leaching measured through lysimeters eventually ceased.
      However, remediation significantly diminished potential soil enzyme activity and
      no trends were observed of the remediated soil recovering its biological
      properties. Soil washing successfully removed available forms of Pb, Zn and Cd
      and thus lowered the human and environmental hazards of the remediated soil;
      however, remediation also extracted the trace elements essential for soil biota.
      In addition to reduced water holding capacity, soil health was not completely
      restored. 

PMID- 24315028
TI  - The interaction of polymer-coated magnetic nanoparticles with seawater.
AB  - Laboratory studies were conducted to evaluate the interaction between bare and
      polymer-coated magnetic nanoparticles (MNPs) with various environmentally
      relevant carrying solutions including natural oceanic seawater with and without
      addition of algal exopolymeric substances (EPS). The MNPs were coated with three
      different stabilising agents, namely gum Arabic (GA-MNP), dextran (D-MNP) and
      carboxymethyl-dextran (CMD-MNP). The colloidal stability of the suspensions was
      evaluated over 48 h and we demonstrated that: (i) hydrodynamic diameters
      increased over time regardless of carrying solution for all MNPs except the GA
      coated ones; however, the relative changes were carrying solution- and coat
      dependent; (ii) polydispersity indexes of the freshly suspended MNPs are below
      0.5 for all coated MNPs, unlike the much higher values obtained for the uncoated
      MNPs; (iii) freshly prepared MNP suspensions (both coated and uncoated) in Milli
      Q (MQ) water show high colloidal stability as indicated by zeta-potential values
      below -30 mV, which however decrease in absolute value within 48 h for all MNPs
      regardless of carrying solution; (iv) EPS seems to "stabilise" the GA-coated and
      the CMD-coated MNPs, but not the uncoated or the D-coated MNPs, which form larger
      aggregates within 48 h; (v) despite this aggregation, iron (Fe)-leaching from
      MNPs is sustained over 48h, but remained within the range of 3-9% of the total
      iron-content of the initially added MNPs regardless of suspension media and
      capping agent. The environmental implications of our findings and
      biotechnological applicability of MNPs are discussed.

PMID- 24315029
TI  - Extraction of polyphenols from black tea--conventional and ultrasound assisted
      extraction.
AB  - Products from plant raw materials gain increasing importance in food-, cosmetics
      and pharmaceutical industry. By way of contrast, due to lack of detailed physico
      chemical fundamentals, existing production processes are economically not optimal
      designed. This leads to a need for deeper understanding of the processes and
      furthermore a systematic process and equipment design for the potentially
      applicable extraction techniques. Using the example of polyphenol extraction from
      black tea (Kenya), the conventional and ultrasound assisted extractions are
      investigated. Here, the state of the art as well as a comparison between the two
      techniques is in focus. Especially, resulting quasi-equilibria and mass transport
      kinetics serves as a criteria. The physico-chemical background is discussed
      taking particle size distributions and scanning electron microscope (SEM)
      measurements into account. Conclusively, process alternatives are projected and
      discussed. Hence, the present study makes influences of ultrasound technique on
      physico-chemical characteristics during extraction a subject of discussion. 

PMID- 24315030
TI  - Dephenolization, dearomatization and detoxification of olive mill wastewater with
      sonication combined with additives and radical scavengers.
AB  - In this study, the effects of some additives [manganese (III) oxide (Mn3O4),
      Cu(+2), Fe(0) and potassium iodate (KIO3)] and some radical scavengers [sodium
      carbonate (Na2CO3), perfluorohexane (C6F14) and t-butyl alcohol (C4H10O)] on the
      sonication of olive mill effluent wastewater (OMW) were investigated since the
      wastewaters of this industry are removed with low efficiencies. The maximum total
      phenol and total aromatic amines (TAAs) removal efficiencies were 88% and 79%,
      respectively, at 60 degrees C with only 150 min sonication. The maximum phenol
      removal was found as 98% with 19 mg L(-1) perfluorohexane and 5 mg L(-1) Fe(0)
      while the maximum TAAs removal was 99% with 16 mg L(-1) KIO3. Catechol, tyrosol,
      quercetin, caffeic acid, 4-methyl catechol, 2-phenylphenol (2-PHE) and 3-phenyl
      phenol (3-PHE) were detected as phenol intermediates while trimethlyaniline,
      aniline, o-toluidine, o-anisidine, dimethylaniline, ethylbenzene and durene were
      identified as TAAs in the OMW. The maximum acute toxicity removals were 96% and
      99% in Vibrio fischeri and Daphnia magna, respectively. Total phenol, TAAs and
      the toxicity in an OMW were removed efficiently and cost-effectively through
      sonication.

PMID- 24315031
TI  - Curtailment: a method to reduce the length of self-report questionnaires while
      maintaining diagnostic accuracy.
AB  - Minimizing the respondent burden and maximizing the classification accuracy of
      tests is essential for efficacious screening for common mental health disorders.
      In previous studies, curtailment of tests has been shown to reduce average test
      length considerably, without loss of accuracy. In the current study, we simulate
      Deterministic (DC) and Stochastic (SC) Curtailment for three self-report
      questionnaires for common mental health disorders, to study the potential gains
      in efficiency that can be obtained in screening for these disorders. The
      curtailment algorithms were applied in an existing dataset of item scores of 502
      help-seeking participants. Results indicate that DC reduces test length by up to
      37%, and SC reduces test length by up to 46%, with only very slight decreases in
      diagnostic accuracy. Compared to an item response theory based adaptive test with
      similar test length, SC provided better diagnostic accuracy. Consequently,
      curtailment may be useful in improving the efficiency of mental health self
      report questionnaires. 

PMID- 24315032
TI  - A reevaluation of the possibility and characteristics in bipolar mania with mixed
      features: a retrospective chart review.
AB  - The aim of the present study was to reevaluate the feasibility of diagnosing a
      mixed features behind bipolar mania and to elucidate the clinical
      characteristics, treatment response, and course of the illness throughout a 12
      month follow-up. The subjects (n=171) were inpatients diagnosed with bipolar I
      disorder, manic, between 2003 and 2010 and were classified into three groups:
      "mania" (n=67), "mania with probable mixed features" (n=79), and "mania with
      definite mixed features" (n=25). Diagnoses were in accordance with the Cincinnati
      criteria, which include the Diagnostic and Statistical Manual of Mental
      Disorders, 4th Edition, Text Revision characteristics for a major depressive
      episode, except for agitation and insomnia. The charts of subjects were
      retrospectively reviewed for demographic and clinical characteristics prior to
      the index episode, clinical data regarding the index episode, and treatment
      courses over a 12-month follow-up period. Subjects in the mania with definite
      mixed features were more likely to be young at admission, to be female, to have a
      familial affective loading, and to have a history of suicidality relative to the
      mania. The results of the present study suggest the need for regular assessment
      of symptoms associated with both polarities during an episode in routine
      practice.

PMID- 24315034
TI  - Divergent task-dependent functional connectivity of executive control and
      salience networks.
AB  - BACKGROUND: Previous studies have demonstrated task-dependent functional
      interactions of a frontal-parietal control system with the competing dorsal
      attention (DA) and default mode networks (DM). However, evidence suggests that
      the frontal-parietal control system is functionally heterogeneous, consisting of
      two distinct sub-networks that demonstrate dissociable intrinsic functional
      connectivity (FC) patterns: a frontal-parietal "executive control network" (CON)
      and a cingulo-opercular "salience network" (SAL). In this study, we aimed to test
      the hypothesis that CON and SAL would show dissociable task-dependent changes in
      connectivity with regard to the competing DA and DM when switching from rest to
      external task performance. METHODS: Nineteen healthy adults underwent four
      functional MRI scans: two during rest and two while performing a global-local
      selective attention task. Seed-based FC defined the CON and SAL. Connectivity
      changes between task and rest states were assessed by analysis of variance. The
      relationship of task-dependent changes in connectivity for each of these networks
      with behavioral measures was also characterized. RESULTS: CON and SAL
      demonstrated distinct stable and task-dependent regional connectivity. Whereas
      CON primarily increased FC with visual cortex regions associated with the DA
      during task performance versus rest, the SAL increased coupling with regions
      belonging to the DM. Greater dissociation between CON and SAL and between regions
      with which they coupled during task was associated with better task accuracy.
      CONCLUSIONS: The divergent task-dependent dynamics of CON and SAL connectivity
      with the anti-correlated DA and DM support distinct functional roles of these two
      "control" networks.

PMID- 24315033
TI  - Lateral rectus superior compartment palsy.
AB  - PURPOSE: To employ magnetic resonance imaging (MRI) to seek evidence of
      compartmental lateral rectus atrophy consistent with a lesion involving selective
      denervation of only 1 of the 2 neuromuscular compartments of the lateral rectus.
      DESIGN: Prospective observational case-control series. METHODS: At a single
      institution, surface coil coronal MRI was obtained at 312 MUm resolution in quasi
      coronal planes 2 mm thick throughout the orbit in 20 normal volunteers and 18
      patients with unilateral lateral rectus palsy fixated monocularly on a target
      placed in central gaze. Maximum cross sections and posterior volumes of the
      superior and inferior lateral rectus compartments were computed and correlated
      with clinical findings. RESULTS: Twelve patients with lateral rectus palsy
      demonstrated symmetric, highly significant 40% reductions in maximum cross
      sections and 50% reductions in posterior volumes from normal for both
      compartments (P < 10(-6) for all comparisons). Six patients with lateral rectus
      palsy had similar significant but asymmetric reductions in those measures only
      for the superior compartment of the affected lateral rectus (P < 10(-4) for all
      comparisons), with insignificant 20%-30% reductions for the inferior compartment
      (P > 0.2 for all comparisons). CONCLUSIONS: A subset of patients with clinical
      lateral rectus palsy may have palsy limited to the superior compartment.
      Paralytic esotropia may be caused by lateral rectus superior compartment palsy
      despite an intact lateral rectus inferior compartment. This finding is consistent
      with evidence supporting independent innervation of the 2 lateral rectus
      neuromuscular compartments.

PMID- 24315035
TI  - Bad thoughts: Brazilian women's responses to mothering while experiencing
      postnatal depression.
AB  - OBJECTIVE: this study explores Brazilian women's experiences of mothering of
      their infants while experiencing postnatal depression. DESIGN: a cross-language
      qualitative descriptive design. METHOD: the sample was composed of 15 women
      diagnosed with postnatal depression in a psychiatric institute in Sao Paulo,
      Brazil. Open-ended interviews were conducted and the data underwent thematic
      analysis. RESULTS: 13 women worried that harm would come to their infants. Seven
      of these women self-identified as potential sources of harm, with two women
      physically hurting their infants. The remaining six women worried about unknown
      agents, such as disease, hurting their infants. In response to these bad
      thoughts, women mothered their infants in one of four ways: (1) transferred care,
      completely delegating this task to family members; (2) shared care, asking family
      members to share the responsibility; (3) sole care, having to look after their
      infants by themselves because they had no available family support; (4) and
      smother care, being hyper-vigilant, constantly watching their infants and not
      trusting infant care to anyone else. CONCLUSIONS: the bad thoughts influenced the
      women's adaptation to mothering their infants. Health professionals should assess
      these thoughts early in the postnatal period and the women's mothering responses
      for the protection of mother and child.

PMID- 24315036
TI  - Two-wave behavior under various conditions of transition area from cancellous
      bone to cortical bone.
AB  - The two-wave phenomenon, the wave separation of a single ultrasonic pulse in
      cancellous bone, is expected to be a useful tool for the diagnosis of
      osteoporosis. However, because actual bone has a complicated structure, precise
      studies on the effect of transition conditions between cortical and cancellous
      parts are required. This study investigated how the transition condition
      influenced the two-wave generation using three-dimensional X-ray CT images of an
      equine radius and a three-dimensional simulation technique. As a result, any
      changes in the boundary between cortical part and trabecular part, which gives
      the actual complex structure of bone, did not eliminate the generation of either
      the primary wave or the secondary wave at least in the condition of clear
      trabecular alignment. The results led us to the possibility of using the two-wave
      phenomenon in a diagnostic system for osteoporosis in cases of a complex
      boundary. 

PMID- 24315039
TI  - Experimental infection of dogs with various Bartonella species or subspecies
      isolated from their natural reservoir.
AB  - Dogs can be infected by a wide variety of Bartonella species. However, limited
      data is available on experimental infection of dogs with Bartonella strains
      isolated from domestic animals or wildlife. We report the inoculation of six dogs
      with Bartonella henselae (feline strain 94022, 16S rRNA type II) in three sets of
      two dogs, each receiving a different inoculum dose), four dogs inoculated with B.
      vinsonii subsp. berkhoffii type I (ATCC strain, one mongrel dog) or type II
      (coyote strain, two beagles and one mongrel) and B. rochalimae (coyote strain,
      two beagles). None of the dogs inoculated with B. henselae became bacteremic, as
      detected by classical blood culture. However, several dogs developed severe
      necrotic lesions at the inoculation site and all six dogs seroconverted within
      one to two weeks. All dogs inoculated with the B. v. berkhoffii and B. rochalimae
      strains became bacteremic at levels comparable to previous experimental
      infections with either a dog isolate or a human isolate. Our data support that
      dogs are likely accidental hosts for B. henselae, just like humans, and are
      efficient reservoirs for both B. v. berkhoffii and B. rochalimae. 

PMID- 24315040
TI  - Hurdles in bacteriophage therapy: deconstructing the parameters.
AB  - Bacterial infections in animals impact our food production, leading to economic
      losses due to food rejection and the need for preventive and curative measures.
      Since the onset of the antibiotic era, the rise of antibiotic-resistant pathogens
      is causing scares in health care and food producing facilities worldwide. In the
      search of new therapeutics, re-evaluation of bacteriophage (phage) therapy, using
      naturally occurring bacterial viruses to tackle infections, is gaining interest.
      Many studies report about phage therapy success, showing the value and power of
      these natural viruses. Although phages carry some interesting traits and their
      basic biology is now well understood, this review argues that phage therapy has
      not revealed all of its secrets and many parameters remain understudied, making
      the outcome of phage therapy highly variable depending on the disease incidence.
      These difficulties include poorly understood mechanisms of phage penetration and
      distribution throughout the body, the variable expression and accessibility of
      phage receptors on the bacterial host in in vivo conditions and the unusual (non
      linear) phage pharmacokinetics. These parameters are not easily measured in
      realistic in vivo settings, but are nevertheless important hurdles to overcome
      the high variability of phage therapy trials. This critical approach is in
      accordance with Goethe's statement; "Difficulties increase the nearer we get to
      the goal". However, since the importance of the goal itself also rises, both
      difficulties and goal justify the need for additional in depth research in this
      domain. 

PMID- 24315038
TI  - Putative human and avian risk factors for avian influenza virus infections in
      backyard poultry in Egypt.
AB  - Highly pathogenic influenza A virus subtype H5N1 causes significant poultry
      mortality in the six countries where it is endemic and can also infect humans.
      Egypt has reported the third highest number of poultry outbreaks (n=1084)
      globally. The objective of this cross-sectional study was to identify putative
      risk factors for H5N1 infections in backyard poultry in 16 villages in Damietta,
      El Gharbia, Fayoum, and Menofia governorates from 2010-2012. Cloacal and tracheal
      swabs and serum samples from domestic (n=1242) and wild birds (n=807) were tested
      for H5N1 via RT-PCR and hemagglutination inhibition, respectively. We measured
      poultry rearing practices with questionnaires (n=306 households) and contact
      rates among domestic and wild bird species with scan sampling. Domestic birds
      (chickens, ducks, and geese, n=51) in three governorates tested positive for H5N1
      by PCR or serology. A regression model identified a significant correlation
      between H5N1 in poultry and the practice of disposing of dead poultry and poultry
      feces in the garbage (F=15.7, p<0.0001). In addition, contact between domestic
      and wild birds was more frequent in villages where we detected H5N1 in backyard
      flocks (F=29.5, p<0.0001).

PMID- 24315037
TI  - Pomegranate juice exacerbates oxidative stress and nigrostriatal degeneration in
      Parkinson's disease.
AB  - Numerous factors contribute to the death of substantia nigra (SN) dopamine (DA)
      neurons in Parkinson's disease (PD). Compelling evidence implicates mitochondrial
      deficiency, oxidative stress, and inflammation as important pathogenic factors in
      PD. Chronic exposure of rats to rotenone causes a PD-like syndrome, in part by
      causing oxidative damage and inflammation in substantia nigra. Pomegranate juice
      (PJ) has the greatest composite antioxidant potency index among beverages, and it
      has been demonstrated to have protective effects in a transgenic model of
      Alzheimer's disease. The present study was designed to examine the potential
      neuroprotective effects of PJ in the rotenone model of PD. Oral administration of
      PJ did not mitigate or prevent experimental PD but instead increased
      nigrostriatal terminal depletion, DA neuron loss, the inflammatory response, and
      caspase activation, thereby heightening neurodegeneration. The mechanisms
      underlying this effect are uncertain, but the finding that PJ per se enhanced
      nitrotyrosine, inducible nitric oxide synthase, and activated caspase-3
      expression in nigral DA neurons is consistent with its potential pro-oxidant
      activity. 

PMID- 24315041
TI  - Sheep persistently infected with Border disease readily transmit virus to calves
      seronegative to BVD virus.
AB  - Bovine viral diarrhea- and Border disease viruses of sheep belong to the highly
      diverse genus pestivirus of the Flaviviridae. Ruminant pestiviruses may infect a
      wide range of domestic and wild cloven-hooved mammals (artiodactyla). Due to its
      economic importance, programs to eradicate bovine viral diarrhea are a high
      priority in the cattle industry. By contrast, Border disease is not a target of
      eradication, although the Border disease virus is known to be capable of also
      infecting cattle. In this work, we compared single dose experimental inoculation
      of calves with Border disease virus with co-mingling of calves with sheep
      persistently infected with this virus. As indicated by seroconversion, infection
      was achieved only in one out of seven calves with a dose of Border disease virus
      that was previously shown to be successful in calves inoculated with BVD virus.
      By contrast, all calves kept together with persistently infected sheep readily
      became infected with Border disease virus. The ease of viral transmission from
      sheep to cattle and the antigenic similarity of bovine and ovine pestiviruses may
      become a problem for demonstrating freedom of BVD by serology in the cattle
      population. 

PMID- 24315042
TI  - Influence of age on the effectiveness of PCV2 vaccination in piglets with high
      levels of maternally derived antibodies.
AB  - Two field studies were conducted to investigate the influence of age on the
      efficacy of vaccination against Porcine Circovirus Diseases (PCVD) in animals
      with high levels of maternally derived antibodies (MDA). A total of 416 piglets
      (Study 1) and 600 piglets (Study 2) were randomly allocated to one of three
      groups. Two groups in each study received a single dose of a PCV2 subunit
      vaccine, one group at 1 week old and the other at 3 weeks of age. The third group
      was left untreated. Animals vaccinated at 3 weeks of age showed a significantly
      higher average daily weight gain and significantly reduced viraemia following
      PCV2 infection than the respective control groups. This difference was not
      observed in pigs vaccinated at 1 week of age. Furthermore, only animals
      vaccinated at 3 weeks of age showed an increased serological response and a
      higher frequency of IgM-positive animals compared with controls. The data
      indicated that PCV2 vaccination in the presence of high MDA levels is efficacious
      when used in 3-week old but not in 1-week old pigs. As the range of MDA titres of
      pigs vaccinated at both 1 and 3 weeks of age were comparable, the data suggest
      that PCV2 vaccine efficacy was independent of the level of MDA. It appears that
      other age-related factors affecting the active and passive transfer of immunity
      may perhaps have interfered with the efficacy of the vaccine in 1-week old
      piglets. These findings have implications for future PCV2 vaccine testing and
      administration strategies. 

PMID- 24315043
TI  - [A rare case of bone metastasis from gastro-intestinal stromal tumour: place of
      radiotherapy].
AB  - Gastro-intestinal stromal tumours are the most common mesenchymal neoplasms of
      the gastrointestinal tract. Their usual metastatic sites are the liver and the
      peritoneum, but gastro-intestinal stromal tumours rarely metastasize to the
      bones. We report the case of a 56-year-old male presenting with bone lesions six
      years after initial surgical resection. We discuss through this paper the
      possibilities of management of these lesions and the place of radiotherapy. 

PMID- 24315044
TI  - Changes to the mechanical properties of the glenohumeral capsule during anterior
      dislocation.
AB  - The glenohumeral joint is the most frequently dislocated major joint in the body,
      and instability due to permanent deformation of the glenohumeral capsule is a
      common pathology. The corresponding change in mechanical properties may have
      implications for the ideal location and extent of plication, which is a common
      clinical procedure used to repair the capsule. Therefore, the objective of this
      study was to quantify the mechanical properties of four regions of the
      glenohumeral capsule after anterior dislocation and compare the properties to the
      normal glenohumeral capsule. Six fresh-frozen cadaveric shoulders were dislocated
      in the anterior direction with the joint in the apprehension position using a
      robotic testing system. After dislocation, mechanical testing was performed on
      the injured glenohumeral capsule by loading the tissue samples in tension and
      shear. An inverse finite element optimization routine was used to simulate the
      experiments and obtain material coefficients for each tissue sample. Cauchy
      stress-stretch curves were then generated to represent the mechanical response of
      each tissue sample to theoretical loading conditions. Based on several
      comparisons (average of the material coefficients, average stress-stretch curve
      for each region, and coefficients representing the average curves) between the
      normal and injured tissue samples, the mechanical properties of the injured
      tissue samples from multiple regions were found to be lower than those of the
      normal tissue in tension but not in shear. This finding indicates that anterior
      dislocation primarily affects the tensile behavior of the glenohumeral capsule
      rather than the shear behavior, and this phenomenon could be caused by plastic
      deformation of the matrix, permanent collagen fiber rotation, and/or collagen
      fiber failure. These results suggest that plication and suturing may not be
      sufficient to return stability to the shoulder after dislocation in all
      individuals. Thus, surgeons may need to perform a procedure that reinforces or
      stiffens the tissue itself, such as reconstruction or augmentation, to improve
      repair procedures. 

PMID- 24315045
TI  - Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting
      stent system with a novel biodegradable coating in de novo coronary lesions: the
      PLUS-ONE first-in-man study.
AB  - BACKGROUND: The Cobra-P drug-eluting stent (DES) system consists of cobalt
      chromium alloy with bio-absorbable siloxane sol-gel matrix coating that elutes
      low dose paclitaxel within 6 months. The aim of this first-in-man trial was to
      evaluate the safety and performance of 2 doses of the Cobra-P DES. METHODS: A
      total of 60 lesions (54 patients) were sequentially assigned to 2 different
      paclitaxel doses: group A (3.7 MUg/18mm, n=30) or group B (8 MUg/18mm, n=30). The
      primary endpoint was MACE at 4 months defined as cardiac death, myocardial
      infarction, and target lesion revascularization. RESULTS: Patient and lesion
      characteristics were matched between the 2 groups except for male sex. MACE at 4
      months was 3.3% and 0% respectively (P=1.000) and at 1-year follow-up remained
      unchanged. In-stent late loss at 4 months was similar in both groups (0.36 +/-
      0.30mm and 0.34 +/- 0.20mm P=.773). CONCLUSIONS: In this FIM study, implantation
      of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol-gel
      coating was proven to be feasible and safe. Moderate neointimal proliferation was
      observed as well as an acceptable MACE rate up to 1 year.

PMID- 24315046
TI  - Percutaneous vertebroplasty compared with conservative treatment in patients with
      chronic painful osteoporotic spinal fractures.
AB  - The efficacy of percutaneous vertebroplasty (PVP) for patients with chronic
      painful osteoporotic compression fractures remains unknown. The purpose of this
      study was to compare the efficacy of PVP and conservative treatment (CT) for pain
      relief and functional outcome in patients with chronic compression fractures and
      persistent pain. Ninety-six patients with chronic compression fractures confirmed
      by MRI and persistent severe pain for 3 months or longer were prospectively
      randomly assigned to undergo PVP (n=46, Group A) or CT (n=50, Group B). The
      primary outcome was pain relief and functional outcome at 1 week, 1 month, 3
      months, 6 months and 1 year. A total of 89 patients (46 in Group A and 43 in
      Group B) completed the 1 year follow-up assessment. Pain relief and functional
      outcomes were significantly better in Group A than in Group B, as determined by
      visual analogue scale scores, Oswestry Disability Index scores, and Roland Morris
      Disability scores at 1 week, 1 month, 3 months, 6 months and 1 year (all
      p<0.001). The final clinical follow-up assessment indicated complete pain relief
      in 39 Group A patients and 15 Group B patients (p<0.001). PVP for patients with
      chronic compression fractures and persistent severe pain was associated with
      better pain relief and improved functional outcomes at 1 year compared to CT.

PMID- 24315047
TI  - Each year 1/1000 people develop RA. Preface.

PMID- 24315048
TI  - Early rheumatoid arthritis: the performance of the 2010 ACR/EULAR criteria for
      diagnosing RA.
AB  - New classification criteria for rheumatoid arthritis (RA) were presented by the
      American College of Rheumatology (ACR) and the European League Against Rheumatism
      (EULAR) in 2010, aiming for early identification of patients at risk of
      developing persistent and erosive arthritis. Since their publication, the
      criteria have been extensively validated against several reference standards, but
      there is still debate regarding how the criteria should be implemented in studies
      and clinical care. We present an overview of the published validation studies and
      discuss the strengths and limitations of the classification criteria, as well as
      whether the criteria are ready for diagnostic purposes in clinical practice. 

PMID- 24315050
TI  - To screen or not to screen: how to find and identify very early arthritis.
AB  - There is accumulating evidence demonstrating that early treatment leads to better
      outcomes in rheumatoid arthritis. In order to be treated early, patients thus
      need to be identified at the earliest possible stage. This means identifying
      patients with rheumatoid arthritis at their earliest clinical signs but it could
      also mean screening for healthy individuals at high risk of developing rheumatoid
      arthritis. The different tools available to screen for these individuals are
      reviewed here and their relevance is discussed. 

PMID- 24315051
TI  - Imaging in early rheumatoid arthritis.
AB  - Imaging in early rheumatoid arthritis (RA) has undergone extraordinary change in
      recent years and new techniques are now available to help the clinician diagnose
      and manage patients much more effectively than previously. While established
      modalities such as plain radiography (X-Ray) remain important, especially for
      detection of erosions and determining the progression of joint damage, there are
      many instances where ultrasound (US), magnetic resonance imaging (MRI) and
      computed tomography (CT) scanning provide added information. MRI and US are now
      used regularly by clinicians to help diagnose RA in the pre-radiographic stage as
      they offer improved visualisation of joint erosions. They also have the potential
      to provide prognostic information as MRI bone oedema/osteitis is linked to the
      later development of erosions and power Doppler ultrasound (PDUS) joint
      positivity is also a predictor of joint damage. Nuclear imaging techniques such
      as single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) are also highly sensitive for detecting joint change in early RA
      and pre-RA but not yet used clinically mainly because of accessibility and
      radiation exposure. MRI, US, scintigraphy, SPECT and PET have all been shown to
      detect sub-clinical joint inflammation in patients in clinical remission, a state
      that is now the goal of most treat-to-target management strategies. Thus, imaging
      may be used to direct therapeutic decision making and MRI is also now being used
      in clinical trials to determine the impact of disease-suppressing therapy on the
      course of synovitis and osteitis. As is the case for all tests, it would be
      unwise to rely completely on any one imaging result, as false positives and
      negatives can occur for all modalities. Thus, the clinician needs to choose the
      most relevant and reliable imaging test, while also striving to minimise patient
      discomfort, radiation burden and economic impact. 

PMID- 24315052
TI  - What is the best treatment strategy for early RA?
AB  - Treatment of early rheumatoid arthritis has to be started very early, when the
      diagnosis is made, preferentially before 6 months of symptoms. Combination
      therapy with conventional disease-modifying anti-rheumatic drugs (DMARDs) with
      low-dose, oral glucocorticoids in the induction phase from the start gives the
      best results. The patient should be monitored systematically, at start between 1
      and 3 months, and the patient should have access to additional visits if a flare
      or arthritis or adverse event occurs. The treatment should aim to remission (no
      tender and swollen joints, no signs of inflammatory activity), which can be
      reached by 60-80% of the patients. Intra-articular glucocorticoid injections as
      part of the treatment strategy increase the suppression of arthritis and retard
      joint destruction. Biological drugs are reserved for patients who have consistent
      active disease and who do not respond to conventional combinations. 

PMID- 24315049
TI  - Can rheumatoid arthritis be prevented?
AB  - The discovery of elevations of rheumatoid arthritis (RA)-related biomarkers prior
      to the onset of clinically apparent RA raises hopes that individuals who are at
      risk of future RA can be identified in a preclinical phase of disease that is
      defined as abnormalities of RA-related immune activity prior to the clinically
      apparent onset of joint disease. Additionally, there is a growing understanding
      of the immunologic processes that are occurring in preclinical RA, as well as a
      growing understanding of risk factors that may be mechanistically related to RA
      development. Furthermore, there are data supporting that treatment of early RA
      can lead to drug-free remission. Taken as a whole, these findings suggest that it
      may be possible to use biomarkers and other factors to accurately identify the
      likelihood and timing of onset of future RA, and then intervene with
      immunomodulatory therapies and/or risk factor modification to prevent the future
      onset of RA in at-risk individuals. Importantly, several clinical prevention
      trials for RA have already been tried, and one is underway. However, while our
      growing understanding of the mechanisms and natural history of RA development may
      be leading us to the implementation of prevention strategies for RA, there are
      still several challenges to be met. These include developing sufficiently
      accurate methods of predicting those at high risk of future RA so that clinical
      trials can be developed based on accurate rates of development of arthritis and
      subjects can be adequately informed of their risk of disease, identifying the
      appropriate interventions and biologic targets for optimal prevention, and
      addressing the psychosocial and economic aspects that are crucial to developing
      broadly applicable prevention measures for RA. These issues notwithstanding,
      prevention of RA may be within reach in the near future. 

PMID- 24315053
TI  - Is there a place for initial treatment with biological DMARDs in the early phase
      of RA?
AB  - The use of biological disease-modifying antirheumatic drugs (bDMARDs) has changed
      the face of rheumatoid arthritis (RA). Achieving remission, normal function and
      prevention of joint damage are now possible for many patients with RA. In
      clinical practice, however, particularly with cost considerations, bDMARDs are
      usually prescribed after failure of one or more conventional synthetic DMARDs.
      With evidence that early treatment has a greater impact than later on, the
      question regarding initial bDMARD therapy and their potential role within a
      window of opportunity to influence disease outcomes remain. The increasing
      emphasis on early diagnosis and research into the preclinical phase of the
      disease also heralds the question, 'Can bDMARDs prevent the development of RA?'
      The aim of this review is to review randomised controlled trials with bDMARDs as
      initial therapy in early RA and to discuss their role in early disease. 

PMID- 24315054
TI  - Outcomes of early rheumatoid arthritis--the WHO ICF framework.
AB  - With the establishment of the new American College of Rheumatology/European
      League Against Rheumatism (ACR/EULAR) 2010 criteria for rheumatoid arthritis (RA)
      to diagnose patients earlier and with the introduction of early and aggressive
      treatment, the current aim is remission resulting in less functional disability,
      halting of radiographic damage, less pain, less fatigue and no loss of
      employment. These outcomes can be related to the World Health Organization
      International Classification of Functioning, Disability and Health (the WHO ICF
      framework). This framework includes the component body functions, body
      structures, activities and participation related to the disease. These components
      are related to each other in a bidirectional way and can be influenced by
      contextual factors including environmental and personal factors. This framework
      can be used to describe trends in RA outcomes and the impact of contextual
      factors on these outcomes. Despite aggressive treatment strategies, patients with
      RA still experience loss of function, pain and fatigue, and a relatively high
      proportion of patients have to take sick leave or become work disabled within the
      first few years of the disease. There is evidence that more stringent definitions
      of remission lead to greater improvement of outcomes and that the aim should be
      sustained remission and not just remission. There is, however, a need for a
      better understanding of the relation between contextual factors and activity and
      participation outcomes to better guide therapy decisions by rheumatologists and
      provide information to patients, families and policymakers about the impact of RA
      on their lives and to the society. The overall aim of this overview is to
      highlight the important contextual factors and consequences that relate to
      outcomes typically measured in RA studies and to demonstrate the additional
      benefits that can be achieved with remission and sustained remission. 

PMID- 24315055
TI  - Estimator design for re-entry targets.
AB  - This study proposes a trajectory estimation scheme for tactical ballistic
      missiles (TBMs). Target information acquired from the ground-based radar system
      is investigated by incorporating input estimation (IE) and extended Kalman
      filtering techniques. In addition to estimate the missile's position and
      velocity, our special focus is put on the estimation of the TBMs evasive
      acceleration and ballistic coefficient. In the demonstrative example, radar
      measurement errors are served as specifications while characterizing the
      acquirable zone of the ground-based radar system. Effect of the proposed design
      is fully verified by examining the estimation performance. 

PMID- 24315056
TI  - Stabilization of an inverted pendulum-cart system by fractional PI-state
      feedback.
AB  - This paper deals with pole placement PI-state feedback controller design to
      control an integer order system. The fractional aspect of the control law is
      introduced by a dynamic state feedback as u(t)=K(p)x(t)+K(I)I(alpha)(x(t)). The
      closed loop characteristic polynomial is thus fractional for which the roots are
      complex to calculate. The proposed method allows us to decompose this polynomial
      into a first order fractional polynomial and an integer order polynomial of order
      n-1 (n being the order of the integer system). This new stabilization control
      algorithm is applied for an inverted pendulum-cart test-bed, and the
      effectiveness and robustness of the proposed control are examined by experiments.

PMID- 24315057
TI  - Process fault isolation based on transfer entropy algorithm.
AB  - Complexity of industrial plants and their stringent environmental and safety
      regulations have necessitated early detection and isolation of process faults.
      All the existing fault isolation methods can be categorized into two general
      groups: model-based and data-based. Transfer entropy is a data-based method for
      measuring propagation direction of disturbance and finding its root cause. In
      this paper, a new transfer entropy-based method is proposed to isolate different
      process faults. The novelty of this paper lies in using the transfer entropy idea
      to generate distinct patterns of information flow among process variables,
      recognize their correlations in the context of the transferred information in any
      abnormal condition, and finally isolate different process faults. The
      experimental results clearly demonstrate the superiority of the proposed method
      to the conventional methods. 

PMID- 24315058
TI  - A new development paradigm post-2015, a comprehensive goal for health that
      includes sexual and reproductive health and rights, and another for gender
      equality.

PMID- 24315059
TI  - Sexual and reproductive health and rights: the next 20 years: Keynote address,
      ICPD beyond 2014: International Conference on Human Rights 7-10 July 2013,
      Netherlands.

PMID- 24315060
TI  - Meeting targets or saving lives: maternal health policy and Millennium
      Development Goal 5 in Nicaragua.
AB  - In support of maternal health, disease-specific and target-oriented global policy
      initiatives, such as in Millennium Development Goal 5, have led to a
      prioritisation of narrow indicators at the expense of more comprehensive
      approaches. In line with global policy, Nicaragua has made skilled attendants and
      institutionalised delivery central to its efforts to achieving MDG5 on maternal
      health. Drawing on ethnographic fieldwork in Nicaragua, involving participant
      observation and interviews with hospital and community health workers, and women
      and their families, this paper critically discusses how target-oriented maternal
      health strategies were manifested in local realities. It shows that Nicaragua's
      brigadistas (community health workers) and parteras (traditional birth
      attendants) have been driven to narrowing their own roles to identifying pregnant
      women and advocating that they have an institutional delivery as one their most
      important tasks, making them agents of MDG 5 target achievement. This has
      engendered fear among brigadistas and parteras of being held individually
      responsible in the event of a maternal death, creating dissatisfaction with their
      role and reducing their motivation. While intended to improve maternal health,
      the pressure to reach targets has unintended negative implications for the
      relationship between women, the local volunteers and the formal health system,
      which needs to be addressed. 

PMID- 24315061
TI  - The right to health in the post-2015 development paradigm.

PMID- 24315062
TI  - Sustainable development goals for global health: facilitating good governance in
      a complex environment.
AB  - Increasing complexity is following in the wake of rampant globalization. Thus,
      the discussion about Sustainable Development Goals (SDGs) requires new thinking
      that departs from a critique of current policy tools in exploration of a
      complexity-friendly approach. This article argues that potential SDGs should:
      treat stakeholders, like states, business and civil society actors, as agents on
      different aggregate levels of networks; incorporate good governance processes
      that facilitate early involvement of relevant resources, as well as equitable
      participation, consultative processes, and regular policy and programme
      implementation reviews; anchor adoption and enforcement of such rules to
      democratic processes in accountable organizations; and include comprehensive
      systems evaluations, including procedural indicators. A global framework
      convention for health could be a suitable instrument for handling some of the
      challenges related to the governance of a complex environment. It could structure
      and legitimize government involvement, engage stakeholders, arrange deliberation
      and decision-making processes with due participation and regular policy review,
      and define minimum standards for health services. A monitoring scheme could
      ensure that agents in networks comply according to whole-systems targets, locally
      defined outcome indicators, and process indicators, thus resolving the paradox of
      government control vs. local policy space. A convention could thus exploit the
      energy created in the encounter between civil society, international
      organizations and national authorities. 

PMID- 24315063
TI  - Universal health coverage: necessary but not sufficient.
AB  - In this article, we highlight key considerations for better addressing sexual and
      reproductive health and rights issues within universal health coverage (UHC),
      particularly in the context of the post-2015 sustainable development agenda. We
      look at UHC as a health, development and health care financing issue, and its
      history. We discuss its limitations as currently understood from a human rights
      perspective, and show why structural barriers to health and the legal and policy
      environment, which are essential to health (particularly to sexual and
      reproductive health and rights), require critical consideration in current
      discussions about health in the post-2015 development framework and must be taken
      into account above and beyond UHC in any future health goal. As a result, we
      suggest that UHC alone will not result in universal access to sexual and
      reproductive health, and certainly not to sexual and reproductive rights.
      Instead, it should be considered as a means to achieving broader health and
      development goals. A goal such as seeking to reach the highest attainable
      standard of health or maximizing healthy lives that is informed by a rights-based
      approach should be the aspiration for the post-2015 development agenda. 

PMID- 24315064
TI  - Ensuring the inclusion of sexual and reproductive health and rights under a
      sustainable development goal on health in the post-2015 human rights framework
      for development.
AB  - Since the 1994 International Conference on Population and Development (ICPD) in
      Cairo placed reproductive health and rights firmly on the international agenda,
      civil society and other advocates have worked ceaselessly to ensure that they
      remain central to women's empowerment and have taken all opportunities to expand
      the framework to include sexual health and rights. When the development process
      changed with the introduction of the Millennium Development Goals (MDGs) in 2000,
      sexual and reproductive health and rights were excluded, and only in 2007 was
      universal access to reproductive health added back in. In 2014 and 2015, the
      future of ICPD Beyond 2014, the MDGs and the post-2015 development framework will
      be decided, following consultations and meetings across the globe. This paper
      takes stock of the key influences on efforts to achieve the ICPD agenda and
      summarises the past, current and planned future events, reports and processes
      between 1994 and 2014, leading up to the determination of the post-2015
      development framework and sustainable development goals. It concludes that the
      one thing we cannot afford to allow is what happened with the MDGs in 2000. We
      must not leave the room empty-handed, but must instead ensure the inclusion of
      sexual and reproductive health and rights as a priority under a new health goal. 

PMID- 24315065
TI  - Embedding sexual and reproductive health and rights in a transformational
      development framework: lessons learned from the MDG targets and indicators.
AB  - This paper explores the intended and unintended consequences of the selection of
      MDG 5 as a global goal, together with its respective targets and indicators, and
      places what happened to MDG 5, and sexual and reproductive health and rights more
      broadly, into the context of the development model that was encoded in the MDGs.
      Over the last decade, as the MDGs increasingly took centre stage in development
      and their use evolved, they were inappropriately converted from global goals into
      national planning targets. This conversion was particularly detrimental in the
      case of MDG 5. It not only created a narrowing in terms of policies and
      programming, but also had an enormous impact on the discourse of development
      itself, reshaping the field in terms of the organization and dissemination of
      knowledge, and underscoring that the process of setting targets and indicators is
      far from neutral but encodes normative values. Looking forward, it is not
      adequate to propose an MDG+ framework based on the same structure. Sexual and
      reproductive health and rights must be placed back into the global discourse,
      using development to empower women and marginalized populations, and to address
      structural inequalities that are fundamental to sustained social change. The new
      development framework should include a strong narrative of social transformation
      in which fit-for-purpose targets and indicators play a role, but do not overtake
      or restrict the broader aims of advancing social, political, and gender justice. 

PMID- 24315066
TI  - No risk, no gain: invest in women and girls by funding advocacy, organizing,
      litigation and work to shift culture.
AB  - The new development framework aspires to merge long-term hopes for environmental,
      political and financial sustainability with international poverty eradication
      goals. Central to this agenda is the promotion and protection of the human rights
      of women and girls. Yet national mechanisms, donors and international development
      agencies often do not fully tackle these issues or confront the accompanying
      politically sensitive, complex issues intermingling religion, socioeconomic
      status, social, cultural and family life. The increasing reliance on private
      investment may further weaken a women's rights approach. The proposed framework
      described in the High-Level Panel of Eminent Persons Report could further
      systematize this problem, even though it improves on the MDGs by expanding
      targets related to women. Success will require support for a potent mix of
      advocacy, movement building and a complex set of ground-based strategies that
      shift cultural practices, laws and policies that harm women and girls. Funding
      for advocacy and interventions that hold firm on human rights is imperative, but
      given the conflicting loyalties of governments and public-private partnerships,
      reliance on either sector may be risky. An analysis of the status of women's
      rights work, infrastructure and donor support in Bangladesh and South Africa
      shows the need for vigilance and long-term investment in effective work. 

PMID- 24315067
TI  - Act global, but think local: accountability at the frontlines.
AB  - There is a worrying divergence between the way that sexual and reproductive
      health and rights problems and solutions are framed in advocacy at the global
      level and the complex reality that people experience in health services on the
      ground. An analysis of approaches to accountability used in advocacy at these
      different levels highlights the different assumptions at play as to how change
      happens. This paper makes the case for a reinvigorated approach to accountability
      that begins with the dynamics of power at the frontlines, where people encounter
      health providers and institutions. Conventional approaches to accountability
      avoid grappling with these dynamics, and as a result, many accountability efforts
      do not lead to transformative change. Implementation science and systems science
      are promising sources for fresh approaches, beginning with the understanding of
      health systems as complex adaptive systems embedded in the broader political
      dynamics of their societies. By drawing insights from disciplines such as
      political economy, ethnography, and organizational change management - and
      applying them creatively to the experience of people in health systems - the
      workings of power can begin to be uncovered and tackled, sharpening
      accountability towards those whose health and rights are at stake and generating
      meaningful change. 

PMID- 24315068
TI  - From Millennium Development Goals to post-2015 sustainable development: sexual
      and reproductive health and rights in an evolving aid environment.
AB  - Using research from country case studies, this paper offers insights into the
      range of institutional and structural changes in development assistance between
      2005 and 2011, and their impact on the inclusion of a sexual and reproductive
      health and rights agenda in national planning environments. At a global level
      during this period, donors supported more integrative modalities of aid - sector
      wide approaches, poverty reduction strategy papers, direct budgetary support -
      with greater use of economic frameworks in decision-making. The Millennium
      Development Goals brought heightened attention to maternal mortality, but at the
      expense of a broader sexual and reproductive health and rights agenda. Advocacy
      at the national planning level was not well linked to programme implementation;
      health officials were disadvantaged in economic arguments, and lacked financial
      and budgetary controls to ensure a connection between advocacy and action. With
      increasing competency in higher level planning processes, health officials are
      now refocusing the post-2015 development goals. If sexual and reproductive health
      and rights is to claim engagement across all its multiple elements, advocates
      need to link them to the key themes of sustainable development: inequalities in
      gender, education, growth and population, but also to urbanisation, migration,
      women in employment and climate change. 

PMID- 24315069
TI  - A global social contract to reduce maternal mortality: the human rights arguments
      and the case of Uganda.
AB  - Progress towards Millennium Development Goal 5a, reducing maternal deaths by 75%
      between 1990 and 2015, has been substantial; however, it has been too slow to
      hope for its achievement by 2015, particularly in sub-Saharan Africa, including
      Uganda. This suggests that both the Government of Uganda and the international
      community are failing to comply with their right-to-health-related obligations
      towards the people of Uganda. This country case study explores some of the key
      issues raised when assessing national and international right-to-health-related
      obligations. We argue that to comply with their shared obligations, national and
      international actors will have to take steps to move forward together. The
      Government of Uganda should not expect additional international assistance if it
      does not live up to its own obligations; at the same time, the international
      community must provide assistance that is more reliable in the long run to create
      the 'fiscal space' that the Government of Uganda needs to increase recurrent
      expenditure for health - which is crucial to addressing maternal mortality. We
      propose that the 'Roadmap on Shared Responsibility and Global Solidarity for
      AIDS, TB and Malaria Response in Africa', adopted by the African Union in July
      2012, should be seen as an invitation to the international community to conclude
      a global social contract for health. 

PMID- 24315070
TI  - Reproductive health financing in Kenya: an analysis of national commitments,
      donor assistance, and the resources tracking process.
AB  - Understanding the flow of resources at the country level to reproductive health
      is essential for effective financing of this key component of health. This paper
      gives a comprehensive picture of the allocation of resources for reproductive
      health in Kenya and the challenges faced in the resource-tracking process. Data
      are drawn from Kenyan budget estimates, reproductive health accounts, and the
      Resource Flows Project database and compare budgets and spending in 2005-06 with
      2009-10. Despite policies and programmes in place since 1994, services for family
      planning, maternity care and infant and child health face serious challenges. As
      regards health financing, the government spends less than the average in sub
      Saharan Africa, while donor assistance and out-of-pocket expenditure for health
      are high. Donor assistance to Kenya has increased over the years, but the
      percentage of funds devoted to reproductive health is lower than it was in 2005.
      We recommend an increase in the budget and spending for reproductive health in
      order to achieve MDG targets on maternal mortality and universal access to
      reproductive health in Kenya. Safety nets for the poor are also needed to reduce
      the burden of spending by households. Lastly, we recommend the generation of more
      comprehensive reproductive health accounts on a regular basis. 

PMID- 24315071
TI  - The Kenyan national response to internationally agreed sexual and reproductive
      health and rights goals: a case study of three policies.
AB  - While priorities for, and decision-making processes on, sexual and reproductive
      health and rights have been determined and led mainly at the international level,
      conflicting power dynamics and responses at the national level in some countries
      have continued to pose challenges for operationalising international agreements.
      This paper demonstrates how these conflicts have played out in Kenya through an
      analysis of three policy-making processes, which led to the Adolescent
      Reproductive Health and Development Policy (2003), the Sexual Offences Act
      (2006), and the National Reproductive Health Policy (2007). The paper is based on
      data from a broader study on the drivers and inhibitors of sexual and
      reproductive health policy reform in Kenya, using a qualitative, case study
      design. Information was gathered through 54 semi-structured, in-depth interviews
      with governmental and civil society policy actors and an extensive review of
      policy documents and media reports. The paper shows that the transformative human
      rights framing of access to sexual and reproductive health, supported by both a
      strong global women's rights movement and progressive governmental and inter
      governmental actors to defeat opposition to sexual and reproductive health and
      rights at the international level, has not been as influential or successful at
      the national level in Kenya, and has made comprehensive national reforms
      difficult to achieve. 

PMID- 24315072
TI  - Brazilians have different views on when abortion should be legal, but most do not
      agree with imprisoning women for abortion.
AB  - Unsafe abortions remain a major public health problem in countries with very
      restrictive abortion laws. In Brazil, parliamentarians - who have the power to
      change the law - are influenced by "public opinion", often obtained through
      surveys and opinion polls. This paper presents the findings from two studies. One
      was carried out in February-December 2010 among 1,660 public servants and the
      other in February-July 2011 with 874 medical students from three medical schools,
      both in Sao Paulo State, Brazil. Both groups of respondents were asked two sets
      of questions to obtain their opinion about abortion: 1) under which circumstances
      abortion should be permitted by law, and 2) whether or not women in general and
      women they knew who had had an abortion should be punished with prison, as
      Brazilian law mandates. The differences in their answers were enormous: the
      majority of respondents were against putting women who have had abortions in
      prison. Almost 60% of civil servants and 25% of medical students knew at least
      one woman who had had an illegal abortion; 85% of medical students and 83% of
      civil servants thought this person(s) should not be jailed. Brazilian
      parliamentarians who are currently reviewing a reform in the Penal Code need to
      have this information urgently. 

PMID- 24315073
TI  - Mobilizing women at the grassroots to shape health policy: a case study of the
      Global Campaign for Microbicides.
AB  - Competition to advance issues on public policy agendas is constant. Political
      scientists agree that professional "policy entrepreneurs" (researchers,
      academics, and bureaucrats) serve as conduits in this process. Grassroots
      advocacy has always been part of the political landscape as non-professional
      people also take on the role of policy advocates or activists, to get specific
      problems and preferred solutions onto public and policy agendas and motivate
      policymakers to take action. The contribution of grassroots advocacy to
      significant policy changes is often under-funded because its impacts are hard to
      isolate and quantify, and are often most evident in retrospect. This paper
      examines the contribution of the Global Campaign for Microbicides to the movement
      to expand the range of HIV prevention options for women and describes how it
      mobilized hundreds of grassroots policy activists around the world to take
      coordinated action on this issue. It reviews the Campaign's accomplishments and
      highlights some of its strengths and weaknesses. Finally, the paper considers the
      value of similar efforts on the part of grassroots advocates seeking to influence
      the post-ICPD and post-2015 development agendas as they are being negotiated.
      Decisions regarding what kind of advocacy work is carried out during this
      process, and by whom and how, will inevitably shape the content of these new
      frameworks. 

PMID- 24315074
TI  - Discrepancies between national maternal mortality data and international
      estimates: the experience of Papua New Guinea.
AB  - Over the past 30 years maternal mortality estimates for Papua New Guinea have
      varied widely. There is no mandatory vital registration in PNG, and 85% of the
      population live in rural areas with limited or no access to health services.
      Demographic Health Survey data for PNG estimates the maternal mortality ratio to
      be 370 deaths per 100,000 live births in 1996 and 733 in 2006, whereas estimates
      based upon mathematical models (as calculated by international bodies) gave
      figures of 930 for 1980 and 230 for 2010. This disparity has been a source of
      considerable confusion for health workers, policy makers and development
      partners. In this study, we compared 2009 facility-based survey data with figures
      from the national Health Information System records. The comparison revealed
      similar maternal mortality ratios: for provincial hospitals (245 and 295),
      government health centres (574 and 386), church agency health centres (624 and
      624), and nationally (394 and 438). Synthesizing these estimates for supervised
      births in facilities and data on unsupervised births from a community-based
      survey in one province indicates a national MMR of about 500. Knowing the
      maternal mortality ratio is a necessary starting point for working out how to
      reduce it. 

PMID- 24315075
TI  - Changes in pregnancy and childbirth practices in remote areas in Lao PDR within
      two generations of women: implications for maternity services.
AB  - This paper sheds light on the inter-generational changes in pregnancy and
      childbirth practices in remote areas of Lao PDR over a period of 30 years. The
      study consisted of focus group discussions with pregnant women aged 14-30,
      mothers and fathers of small children, and older women aged 40+ in six rural
      communities in two districts. Childbirth practices were gradually evolving and
      changing - most dramatically illustrated by the transition from forest-based to
      home-based delivery, and a few health facility-based deliveries when
      complications occurred. Today's generation of women aged 40+ did not recommend
      all the practices of their mothers, but saw the need to adapt due to the social
      and medical risks they had experienced, especially high rates of neonatal death.
      Their daughters are doing the same. The increase in home-based deliveries should
      be regarded as significant progress in this setting in rural Laos. Understanding
      how young women interpret their options and incorporating that knowledge and the
      experience of successful local outreach programmes into health system policy and
      practice for maternity care, e.g. by strengthening the skills of community-based
      health workers, could contribute to improving maternal and neonatal survival and
      reducing health inequalities. 

PMID- 24315077
TI  - [Macrocheilia, granulomatous cheilitis and Crohn's disease].
AB  - Granulomatous cheilitis is a rare disease included among the orofacial
      granulomatoses. It is characterized by a idiopathic chronic inflammation of the
      labial mucosa (macrochelia), which takes the form of episodic and progressive
      outbreaks. In 10% of patients, it is associated with Crohn's disease. We report
      the presentation, evaluation and treatment of a case of granulomatous cheilitis
      which appearted two years after the onset of Crohn's disease. We conclude that
      granulomatous cheilitis is rare in children, with few reported cases, although
      probably underdiagnosed because of lack of awareness. The diagnosis of
      granulomatous cheilitis is clinical, although the histological evaluation is a
      determining factor. After making the diagnosis a comprehensive assessment of the
      patient is recommended, to rule out the other associated syndromes described in
      the literature. 

PMID- 24315078
TI  - [Low back pain of unfavourable progression].
AB  - We present the case of a patient with chronic low back pain with an unfavourable
      progression despite the prescribed pharmacological treatment. The patient had
      symptoms associated with compression of the sciatic nerve in an atypical area. As
      it passed through the piriformis muscle, it was diagnosed as piriformis muscle
      syndrome. This diagnosis was based on the clinical signs and symptoms and the
      determination of the tests performed, with the imaging tests being absolutely
      normal. Treatment is basically with non-steroidal anti-inflammatory drugs, muscle
      relaxants and stretching exercises of this muscle. 

PMID- 24315076
TI  - The association between childhood trauma and lipid levels in an adult low-income,
      minority population.
AB  - BACKGROUND: The objective of this study is to investigate the association between
      childhood trauma and lipid profiles in adults from a highly traumatized
      population at-risk for cardiovascular disease. METHOD: We recruited 452
      participants, primarily African-American and of low socioeconomic status, from
      general medical clinics in a large urban hospital. We performed direct
      comparisons, univariate analysis of variance and regression analyses together and
      separated by sex, examining the associations of child abuse, body mass index,
      lipid lowering drug use, blood pressure, age, and substance use to HDL levels and
      HDL/LDL ratios. RESULTS: A history of moderate to severe levels of childhood
      trauma and abuse was associated with a significant decrease in HDL levels (P <=
      .01) and HDL/LDL ratios (P <= .001) relative to males with low levels of abuse.
      This relationship held when the status of lipid-lowering drugs was considered.
      When controlling for age, substance abuse, tobacco use, and adult trauma, the
      effects of childhood trauma remained significant. We found a significant child
      abuse by sex interaction on HDL/LDL ratios [F(1,369)=13.0, P <= .0005] consistent
      with a differential effect of trauma on dyslipidemia in male but not female
      subjects. CONCLUSIONS: Our data suggest that childhood trauma exposure, obtained
      with self-report measures, may contribute to increased risk of cardiovascular
      disease by way of stress-mediated alterations of lipid concentration and
      composition in male, but not female, subjects.

PMID- 24315079
TI  - [Klippel-Feil syndrome, a rare cervicalgia].
AB  - Cervicalgia is defined as the presence of pain in the neck region, and can
      radiate to the shoulders, upper limbs or back. It is a source of frequent visits
      to Primary Care, and more than half of the general population will suffer neck
      pain at some point in their life. Klippel-Feil syndrome is an exceptional cause
      of cervicalgia. It belongs to the group of so-called malformations of the hold
      down skull-cervical congenital disease. Klippel-Feil syndrome is a complex
      disease entity characterized by the fusion of two or more vertebrae, and may also
      be associated with other bone and visceral disorders. The characteristic clinical
      triad consists of short-neck, implantation below the hair in the occipital
      region, and limitation of cervical mobility. However, this clinical picture is
      present in less than 50% of these patients.

PMID- 24315080
TI  - [Thyrotoxic hypokalemic periodic paralysis. A case report].
AB  - Thyrotoxic hypokalemic periodic paralysis is an uncommon complication of
      thyrotoxicosis, characterized by attacks of generalized muscular weakness
      associated with hypokalemia in patients with hyperthyroidism, most frequently
      with Graves-Basedow disease. Treatment with antithyroid drugs and potassium
      supplements reversed the symptoms and the episodes of acute muscular weakness did
      not reappear. 

PMID- 24315081
TI  - [Screening program for the early diagnosis of colorectal cancer in the Canary
      Islands: presentation of a case].
AB  - Colorectal cancer is the second leading cause of cancer death in Spain. The main
      objective of screening programs is the early detection, or even prevention of the
      development, of colon cancer, as well as the mortality that results from it. If
      caught early, it is easy to treat and the chances of cure are high. In 2009 only
      six regions in Spain, among which included the Autonomous Community of the Canary
      Islands, started this screening program. We report the case of a patient, who
      after screening for colorectal cancer, was diagnosed with adenocarcinoma of the
      rectosigmoid.

PMID- 24315082
TI  - [Edematous and painful leg. Pathophysiology in the spotlight: presentation of a
      case].
AB  - We report on a 74-year-old woman visually impaired and under treatment with
      amlodipine, valsartan and thyroid hormone. The patient complained of her unique,
      edematous and painful leg after a local trauma. The worsening was slow and
      gradual, affecting walk and state of mind. Several unsuccessful diagnoses were
      done before suspecting and confirming a Complex Regional Pain Syndrome. Edema
      disappeared dramatically after amlodipine empirical discontinuation. Pain
      improved gradually with rehabilitation exercises but, mainly, after gaining
      skills and self-esteem due to cataract surgery of her unique functional eye. It
      was necessary to decrease thyroid hormone dosage after a long lasting balance.
      The sympathetic nervous system role of the case is discussed. 

PMID- 24315083
TI  - [Horseshoe kidney, stone disease and prostate cancer: a case presentation].
AB  - The horseshoe kidney is the most common congenital renal fusion anomalies. It
      occurs in 0.25% of the population, or 1 in every 400 people. It is more frequent
      in males (ratio 2:1). The most observed complication of horseshoe kidney is stone
      disease, although there may be others such as, abdominal pain, urinary
      infections, haematuria, hydronephrosis, trauma and tumours (most commonly
      associated with hypernephroma and Wilms tumour). We describe a case of a male
      patient with horseshoe kidney, stone disease and adenocarcinoma of the prostate.
      One carrier of this condition who suffered a transitional cell carcinoma of the
      prostate was found in a review of the literature. 

PMID- 24315084
TI  - The proximal bronchoplasty retrieval technique for removal of embedded distal
      airway foreign bodies.
AB  - OBJECTIVES: To describe a novel technique for removal of embedded distal airway
      foreign bodies with emphasis on procedural steps and management. METHODS: The
      proximal bronchoplasty retrieval (PBR) technique is described including
      indications, rationale, surgical technique, and clinical decision making. Two
      representative cases are described in detail in order to demonstrate the
      technique. RESULTS: The PBR technique was successfully used to remove the two
      described embedded distal airway foreign bodies after other attempts had failed.
      CONCLUSION: Airway foreign bodies which have been present for several days or
      weeks are associated with edema and granulation tissue which often embeds the
      foreign body and may prevent removal due to proximal airway narrowing. We present
      a novel technique using endoscopic balloon dilation bronchoplasty to enlarge the
      airway proximal to the foreign body and enable removal with two example cases
      presented herein. The PBR technique allowed for removal of otherwise "stuck"
      distal airway foreign bodies.

PMID- 24315085
TI  - Improvements to alpha-particle spectrometry techniques.
AB  - Improvements to the conventional methods for alpha-particle spectrometry
      measurement and analysis have recently been implemented in our laboratory. They
      include the application of corrections for energy drift in long-duration
      measurements, the development and application of an efficient deconvolution
      method for complex alpha spectra using the new computer code ALFITeX, an alpha
      gamma coincidence system using a dual-parameter multichannel analyzer, and the
      digitization of this coincidence system. 

PMID- 24315086
TI  - Comparison of digital signal processing modules in gamma-ray spectrometry.
AB  - Commercial digital signal-processing modules have been tested for their
      applicability to gamma-ray spectrometry. The tests were based on the same n-type
      high purity germanium detector. The spectrum quality was studied in terms of
      energy resolution and peak area versus shaping parameters, using a Eu-152 point
      source. The stability of a reference peak count rate versus the total count rate
      was also examined. The reliability of the quantitative results is discussed for
      their use in measurement at the metrological level. 

PMID- 24315087
TI  - Foundations of biomolecular modeling.
AB  - The 2013 Nobel Prize in Chemistry has been awarded to Martin Karplus, Michael
      Levitt, and Arieh Warshel for "development of multiscale models for complex
      chemical systems." The honored work from the 1970s has provided a foundation for
      the widespread activities today in modeling organic and biomolecular systems. 

PMID- 24315088
TI  - A prize for membrane magic.
AB  - The 2013 Nobel Prize in Physiology or Medicine has been awarded to James Rothman,
      Randy Schekman, and Thomas Sudhof "for their discoveries of machinery regulating
      vesicle traffic, a major transport system in our cells". I present a personal
      view of the membrane trafficking field, highlighting the contributions of these
      three Nobel laureates in a historical context.

PMID- 24315089
TI  - Structure modeling using genetically engineered crosslinking.
AB  - Class B G-protein-coupled receptors are exciting drug targets, yet the structure
      of a complete receptor bound to a peptide agonist has remained elusive. Coin et
      al. present a model of the receptor CRF1R bound to its native ligand based on
      partial structures and 44 spatial constraints revealed by new crosslinking
      approaches.

PMID- 24315090
TI  - Trp'ing tuberculosis.
AB  - IFN-gamma-activated macrophages attempt to limit pathogen growth through
      tryptophan starvation. Zhang et al. demonstrate that Mycobacterium tuberculosis
      responds to this threat by synthesizing its own tryptophan. Genetic and chemical
      inhibition of this pathway reduces mycobacterial survival, revealing a new immune
      dependent drug target for tuberculosis.

PMID- 24315091
TI  - Glucocorticoid rhythm renders female mice more daring.
AB  - Glucocorticoids, which have been implied in mood modulation, display robust
      diurnal oscillations in the blood. But does their circadian rhythm regulate mood
      swings? Ikeda et al. now identify a paracrine signaling pathway in the adrenal
      cortex that potentiates the daily amplitude of plasma glucocorticoids and renders
      female mice braver.

PMID- 24315092
TI  - snRNA catalysts in the spliceosome's ancient core.
AB  - The spliceosome, an assembly of snRNAs and proteins, catalyzes the removal of
      introns from premessenger RNAs. A new study identifies specific phosphates in the
      U2-U6 snRNA complex that position two catalytic metals. Remarkably, these
      correspond precisely to metal-binding phosphates in a homologous structure of
      Group II self-splicing introns, long proposed to be the ribozyme progenitor of
      spliceosome. 

PMID- 24315093
TI  - Autophagy-mediated tumor promotion.
AB  - Mouse models for cancer are revealing novel cancer-promoting roles for autophagy.
      Autophagy promotes tumor growth by suppressing the p53 response, maintaining
      mitochondrial function, sustaining metabolic homeostasis and survival in stress,
      and preventing diversion of tumor progression to benign oncocytomas. 

PMID- 24315094
TI  - Incisive imaging and computation for cellular mysteries: lessons from abscission.
AB  - The final cleavage event that terminates cell division, abscission of the small,
      dense intercellular bridge, has been particularly challenging to resolve. Here,
      we describe imaging innovations that helped answer long-standing questions about
      the mechanism of abscission. We further explain how computational modeling of
      high-resolution data was employed to test hypotheses and generate additional
      insights. We present the model that emerges from application of these
      complimentary approaches. Similar experimental strategies will undoubtedly reveal
      exciting details about other underresolved cellular structures. 

PMID- 24315095
TI  - Integrated structural analysis of the human nuclear pore complex scaffold.
AB  - The nuclear pore complex (NPC) is a fundamental component of all eukaryotic cells
      that facilitates nucleocytoplasmic exchange of macromolecules. It is assembled
      from multiple copies of about 30 nucleoporins. Due to its size and complex
      composition, determining the structure of the NPC is an enormous challenge, and
      the overall architecture of the NPC scaffold remains elusive. In this study, we
      have used an integrated approach based on electron tomography, single-particle
      electron microscopy, and crosslinking mass spectrometry to determine the
      structure of a major scaffold motif of the human NPC, the Nup107 subcomplex, in
      both isolation and integrated into the NPC. We show that 32 copies of the Nup107
      subcomplex assemble into two reticulated rings, one each at the cytoplasmic and
      nuclear face of the NPC. This arrangement may explain how changes of the diameter
      are realized that would accommodate transport of huge cargoes. 

PMID- 24315096
TI  - A super-assembly of Whi3 encodes memory of deceptive encounters by single cells
      during yeast courtship.
AB  - Cellular behavior is frequently influenced by the cell's history, indicating that
      single cells may memorize past events. We report that budding yeast permanently
      escape pheromone-induced cell-cycle arrest when experiencing a deceptive mating
      attempt, i.e., not reaching their putative partner within reasonable time. This
      acquired behavior depends on super-assembly and inactivation of the G1/S
      inhibitor Whi3, which liberates the G1 cyclin Cln3 from translational inhibition.
      Super-assembly of Whi3 is a slow response to pheromone, driven by polyQ and polyN
      domains, counteracted by Hsp70, and stable over generations. Unlike prion
      aggregates, Whi3 super-assemblies are not inherited mitotically but segregate to
      the mother cell. We propose that such polyQ- and polyN-based elements, termed
      here mnemons, act as cellular memory devices to encode previous environmental
      conditions. 

PMID- 24315097
TI  - Proteolysis inside the membrane is a rate-governed reaction not driven by
      substrate affinity.
AB  - Enzymatic cleavage of transmembrane anchors to release proteins from the membrane
      controls diverse signaling pathways and is implicated in more than a dozen
      diseases. How catalysis works within the viscous, water-excluding, two
      dimensional membrane is unknown. We developed an inducible reconstitution system
      to interrogate rhomboid proteolysis quantitatively within the membrane in real
      time. Remarkably, rhomboid proteases displayed no physiological affinity for
      substrates (K(d) ~190 MUM/0.1 mol%). Instead, ~10,000-fold differences in
      proteolytic efficiency with substrate mutants and diverse rhomboid proteases were
      reflected in k(cat) values alone. Analysis of gate-open mutant and solvent
      isotope effects revealed that substrate gating, not hydrolysis, is rate limiting.
      Ultimately, a single proteolytic event within the membrane normally takes
      minutes. Rhomboid intramembrane proteolysis is thus a slow, kinetically
      controlled reaction not driven by transmembrane protein-protein affinity. These
      properties are unlike those of other studied proteases or membrane proteins but
      are strikingly reminiscent of one subset of DNA-repair enzymes, raising important
      mechanistic and drug-design implications.

PMID- 24315098
TI  - A special population of regulatory T cells potentiates muscle repair.
AB  - Long recognized to be potent suppressors of immune responses, Foxp3(+)CD4(+)
      regulatory T (Treg) cells are being rediscovered as regulators of
      nonimmunological processes. We describe a phenotypically and functionally
      distinct population of Treg cells that rapidly accumulated in the acutely injured
      skeletal muscle of mice, just as invading myeloid-lineage cells switched from a
      proinflammatory to a proregenerative state. A Treg population of similar
      phenotype accumulated in muscles of genetically dystrophic mice. Punctual
      depletion of Treg cells during the repair process prolonged the proinflammatory
      infiltrate and impaired muscle repair, while treatments that increased or
      decreased Treg activities diminished or enhanced (respectively) muscle damage in
      a dystrophy model. Muscle Treg cells expressed the growth factor Amphiregulin,
      which acted directly on muscle satellite cells in vitro and improved muscle
      repair in vivo. Thus, Treg cells and their products may provide new therapeutic
      opportunities for wound repair and muscular dystrophies.

PMID- 24315099
TI  - Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing.
AB  - Bacteria that cause disease rely on their ability to counteract and overcome host
      defenses. Here, we present a genome-scale study of Mycobacterium tuberculosis
      (Mtb) that uncovers the bacterial determinants of surviving host immunity, sets
      of genes we term "counteractomes." Through this analysis, we found that CD4 T
      cells attempt to contain Mtb growth by starving it of tryptophan--a mechanism
      that successfully limits infections by Chlamydia and Leishmania, natural
      tryptophan auxotrophs. Mtb, however, can synthesize tryptophan under stress
      conditions, and thus, starvation fails as an Mtb-killing mechanism. We then
      identify a small-molecule inhibitor of Mtb tryptophan synthesis, which converts
      Mtb into a tryptophan auxotroph and restores the efficacy of a failed host
      defense. Together, our findings demonstrate that the Mtb immune counteractomes
      serve as probes of host immunity, uncovering immune-mediated stresses that can be
      leveraged for therapeutic discovery.

PMID- 24315100
TI  - Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen
      receptor blockade.
AB  - The treatment of advanced prostate cancer has been transformed by novel
      antiandrogen therapies such as enzalutamide. Here, we identify induction of
      glucocorticoid receptor (GR) expression as a common feature of drug-resistant
      tumors in a credentialed preclinical model, a finding also confirmed in patient
      samples. GR substituted for the androgen receptor (AR) to activate a similar but
      distinguishable set of target genes and was necessary for maintenance of the
      resistant phenotype. The GR agonist dexamethasone was sufficient to confer
      enzalutamide resistance, whereas a GR antagonist restored sensitivity. Acute AR
      inhibition resulted in GR upregulation in a subset of prostate cancer cells due
      to relief of AR-mediated feedback repression of GR expression. These findings
      establish a mechanism of escape from AR blockade through expansion of cells
      primed to drive AR target genes via an alternative nuclear receptor upon drug
      exposure. 

PMID- 24315101
TI  - Modulation of circadian glucocorticoid oscillation via adrenal opioid-CXCR7
      signaling alters emotional behavior.
AB  - Circulating glucocorticoid levels oscillate with a robust circadian rhythm, yet
      the physiological relevance of this rhythmicity remains unclear. Here, we show
      that modulation of circadian glucocorticoid oscillation by enhancing its
      amplitude leads to anxiolytic-like behavior. We observed that mice with adrenal
      subcapsular cell hyperplasia (SCH), a common histological change in the adrenals,
      are less anxious than mice without SCH. This behavioral change was found to be
      dependent on the higher amplitude of glucocorticoid oscillation, although the
      total glucocorticoid secretion is not increased in these mice. Genetic and
      pharmacologic experiments demonstrated that intermediate opioid peptides secreted
      from SCH activate CXCR7, a beta-arrestin-biased G-protein-coupled receptor
      (GPCR), to augment circadian oscillation of glucocorticoid levels in a paracrine
      manner. Furthermore, recapitulating this paracrine axis by subcutaneous
      administration of a synthetic CXCR7 ligand is sufficient to induce anxiolytic
      like behavior. Adrenocortical beta-arrestin-biased GPCR signaling is a potential
      target for modulating circadian glucocorticoid oscillation and emotional
      behavior.

PMID- 24315102
TI  - Parallel, redundant circuit organization for homeostatic control of feeding
      behavior.
AB  - Neural circuits for essential natural behaviors are shaped by selective pressure
      to coordinate reliable execution of flexible goal-directed actions. However, the
      structural and functional organization of survival-oriented circuits is poorly
      understood due to exceptionally complex neuroanatomy. This is exemplified by AGRP
      neurons, which are a molecularly defined population that is sufficient to rapidly
      coordinate voracious food seeking and consumption behaviors. Here, we use cell
      type-specific techniques for neural circuit manipulation and projection-specific
      anatomical analysis to examine the organization of this critical homeostatic
      circuit that regulates feeding. We show that AGRP neuronal circuits use a
      segregated, parallel, and redundant output configuration. AGRP neuron axon
      projections that target different brain regions originate from distinct
      subpopulations, several of which are sufficient to independently evoke feeding.
      The concerted anatomical and functional analysis of AGRP neuron projection
      populations reveals a constellation of core forebrain nodes, which are part of an
      extended circuit that mediates feeding behavior. 

PMID- 24315103
TI  - Targeting a dual detector of skin and CO2 to modify mosquito host seeking.
AB  - Female mosquitoes that transmit deadly diseases locate human hosts by detecting
      exhaled CO2 and skin odor. The identities of olfactory neurons and receptors
      required for attraction to skin odor remain a mystery. Here, we show that the CO2
      sensitive olfactory neuron is also a sensitive detector of human skin odorants in
      both Aedes aegypti and Anopheles gambiae. We demonstrate that activity of this
      neuron is important for attraction to skin odor, establishing it as a key target
      for intervention. We screen ~0.5 million compounds in silico and identify several
      CO2 receptor ligands, including an antagonist that reduces attraction to skin and
      an agonist that lures mosquitoes to traps as effectively as CO2. Analysis of the
      CO2 receptor ligand space provides a foundation for understanding mosquito host
      seeking behavior and identifies odors that are potentially safe, pleasant, and
      affordable for use in a new generation of mosquito control strategies worldwide.

PMID- 24315104
TI  - Genome-wide map of nuclear protein degradation shows NCoR1 turnover as a key to
      mitochondrial gene regulation.
AB  - Transcription factor activity and turnover are functionally linked, but the
      global patterns by which DNA-bound regulators are eliminated remain poorly
      understood. We established an assay to define the chromosomal location of DNA
      associated proteins that are slated for degradation by the ubiquitin-proteasome
      system. The genome-wide map described here ties proteolysis in mammalian cells to
      active enhancers and to promoters of specific gene families. Nuclear-encoded
      mitochondrial genes in particular correlate with protein elimination, which
      positively affects their transcription. We show that the nuclear receptor
      corepressor NCoR1 is a key target of proteolysis and physically interacts with
      the transcription factor CREB. Proteasome inhibition stabilizes NCoR1 in a site
      specific manner and restrains mitochondrial activity by repressing CREB-sensitive
      genes. In conclusion, this functional map of nuclear proteolysis links chromatin
      architecture with local protein stability and identifies proteolytic derepression
      as highly dynamic in regulating the transcription of genes involved in energy
      metabolism. 

PMID- 24315105
TI  - Circadian control of global gene expression by the cyanobacterial master
      regulator RpaA.
AB  - The cyanobacterial circadian clock generates genome-wide transcriptional
      oscillations and regulates cell division, but the underlying mechanisms are not
      well understood. Here, we show that the response regulator RpaA serves as the
      master regulator of these clock outputs. Deletion of rpaA abrogates gene
      expression rhythms globally and arrests cells in a dawn-like expression state.
      Although rpaA deletion causes core oscillator failure by perturbing clock gene
      expression, rescuing oscillator function does not restore global expression
      rhythms. We show that phosphorylated RpaA regulates the expression of not only
      clock components, generating feedback on the core oscillator, but also a small
      set of circadian effectors that, in turn, orchestrate genome-wide transcriptional
      rhythms. Expression of constitutively active RpaA is sufficient to switch cells
      from a dawn-like to a dusk-like expression state as well as to block cell
      division. Hence, complex global circadian phenotypes can be generated by
      controlling the phosphorylation of a single transcription factor. 

PMID- 24315107
TI  - [French law related to patient's rights and end of life: pediatric intensive care
      unit's health professionals' opinions].
AB  - INTRODUCTION AND OBJECTIVES: To identify the knowledge of caregivers of pediatric
      intensive care units (PICUs) on the French law related to patients' rights and
      end of life, their views on withholding/withdrawing life-sustaining treatment
      (WWLST) decisions, and their feelings about how these decisions were made and
      implemented. MATERIALS AND METHODS: A multicenter survey in 24 French PICUs
      during the fourth trimester 2010. RESULTS: One thousand three hundred and thirty
      nine professional healthcare workers (1005 paramedics and 334 physicians)
      responded. Over 85% of caregivers had good knowledge of the WWLST decision-making
      processes required by law. More than 80% of caregivers accepted mechanical
      ventilation, hemodiafiltration, or hemodynamic support withdrawal or withholding.
      Nevertheless, the withdrawal of artificial nutrition and hydration generated
      reluctance or opposition for the majority of respondents. While paramedics'
      participation in the decision-making process was deemed necessary by all
      caregivers, paramedics found more often than physicians that they were
      insufficiently involved. The quality of end-of-life care was judged very
      positively by caregivers. The answers on how WWLST was applied suggest very
      different interpretations of the law. Some caregivers respect the principles of
      palliative care as stated in the public health code and 40% of doctors and 64% of
      caregivers consider it "acceptable" to hasten death if resulting from a
      collaborative decision-making process. CONCLUSION: This study is the first to
      show that caregivers of French PICUs have good knowledge of the French law
      concerning the end of life. Yet, there is still confusion about the limits of
      practice during the end-of-life period.

PMID- 24315106
TI  - Using optogenetics to interrogate the dynamic control of signal transmission by
      the Ras/Erk module.
AB  - The complex, interconnected architecture of cell-signaling networks makes it
      challenging to disentangle how cells process extracellular information to make
      decisions. We have developed an optogenetic approach to selectively activate
      isolated intracellular signaling nodes with light and use this method to follow
      the flow of information from the signaling protein Ras. By measuring dose and
      frequency responses in single cells, we characterize the precision, timing, and
      efficiency with which signals are transmitted from Ras to Erk. Moreover, we
      elucidate how a single pathway can specify distinct physiological outcomes: by
      combining distinct temporal patterns of stimulation with proteomic profiling, we
      identify signaling programs that differentially respond to Ras dynamics,
      including a paracrine circuit that activates STAT3 only after persistent (>1 hr)
      Ras activation. Optogenetic stimulation provides a powerful tool for analyzing
      the intrinsic transmission properties of pathway modules and identifying how they
      dynamically encode distinct outcomes.

PMID- 24315109
TI  - [Systolic murmur with dyspnea at 2 years of age].

PMID- 24315110
TI  - Meta-analysis of prognostic implications of dyspnea versus chest pain in patients
      referred for stress testing.
AB  - Previous studies have suggested that patients with dyspnea referred for stress
      testing have high mortality. However, it is not clear whether this is explained
      by high rates of ischemia. The aim of the present study was to evaluate the
      incidence of ischemia in patients with dyspnea compared with patients with chest
      pain referred for stress testing and assess the outcomes of such patients. We
      systematically searched the electronic databases, MEDLINE, PubMed, EMBASE, and
      the Cochrane Library, until December 2012 to identify studies of patients with
      known or suspected coronary artery disease undergoing stress testing. We
      extracted data on group-specific incidence of stress-induced ischemia and all
      cause mortality. In our analyses, we identified and included 6 studies that
      evaluated a total of 5,753 patients with dyspnea and 24,491 patients with chest
      pain as the clinical indication for stress testing. There was no statistically
      significant difference in the incidence of ischemia on stress imaging in patients
      with dyspnea compared with patients with chest pain (37.4% vs 30.2%, odds ratio
      1.43, 95% confidence interval 0.99 to 2.06, p = 0.06). However, during the follow
      up period, patients with dyspnea had higher all-cause mortality rates compared
      with patients with chest pain (annual mortality 4.9% vs 2.3%), with odds ratio of
      2.57 (95% confidence interval 1.75 to 3.76, p <0.001). In conclusion, in patients
      undergoing stress testing, those evaluated for dyspnea had a significant increase
      in all-cause mortality but did not have higher rates of ischemia compared with
      patients presenting with chest pain. Clinicians evaluating patients with self
      reported dyspnea should be aware that these patients represent a high-risk group
      with increased risk of mortality.

PMID- 24315111
TI  - Impact of diabetes mellitus on early and midterm outcomes after transcatheter
      aortic valve implantation (from a multicenter registry).
AB  - Several clinical and procedural factors have been identified as predictors of
      early and midterm events after transcatheter aortic valve implantation (TAVI),
      but incidence and prognostic impact of diabetes mellitus (DM), especially insulin
      treated, on short- and midterm outcomes remain to be defined. All consecutive
      patients who underwent TAVI at our institutions were enrolled and stratified
      according to DM status. All-cause mortality at 30 days or in hospital and at
      follow-up was the primary end point, whereas periprocedural complications, rates
      of myocardial infarction, stroke, and reintervention at follow-up were the
      secondary ones. All end points were adjudicated according to the Valve Academic
      Research Consortium definitions. In all, 511 patients were enrolled: 361 without
      DM, 78 with orally treated DM, and 72 with insulin-treated DM. Orally treated DM
      patients were more frequently women, whereas insulin-treated DM patients were
      younger. Thirty-day Valve Academic Research Consortium mortality was not
      significantly higher in patients with orally treated DM and insulin-treated DM
      compared with patients without diabetes (6.4%, 9.7%, and 4.7%, p = 0.09).
      Bleedings, vascular complications, postprocedural acute kidney injury, and
      periprocedural strokes were not significantly different in the 3 groups. At
      midterm follow-up (median 400 days), patients with insulin-treated DM had a
      significantly higher mortality rate (33.3% vs 18.6%, p = 0.01) and higher
      myocardial infarction incidence (8.3% vs 1.4%, p = 0.002) if compared with
      patients without diabetes. Strokes and reinterventions at follow-up were similar
      in the 3 groups. After multivariable adjustment, insulin-treated DM was
      independently correlated with death (hazard ratio 2, 95% confidence interval 1.3
      to 3.3) and myocardial infarction (hazard ratio 3.73, 95% confidence interval 1.1
      to 13). In conclusion, DM does not significantly affect rates of complications in
      patients who underwent TAVI. Insulin-treated DM, but not orally treated DM, is
      independently associated with death and myocardial infarction at midterm follow
      up and should be included into future TAVI-dedicated scores.

PMID- 24315112
TI  - Comparison of epicardial fat volume by computed tomography in black versus white
      patients with acute chest pain.
AB  - Disparities in the risk of coronary artery disease (CAD) between races may be
      influenced by differences in the thoracic adipose tissue. We compared computed
      tomography (CT)-derived volumes of epicardial adipose tissue (EAT), mediastinal
      adipose tissue (MAT), and pericoronary fat thickness (PFT) and correlations with
      CAD between black and white patients. This institutional review board-approved
      Health Insurance Portability and Accountability Act-compliant study included 372
      age- and gender-matched black versus white patients (186 black, 54 +/- 11 years,
      50% men; 186 white, 54 +/- 11 years, 50% men) who underwent CT for chest pain
      evaluation. EAT, MAT, and PFT were measured. The amount of coronary calcium was
      quantified as calcium score. CAD was defined as >=50% coronary artery narrowing.
      EAT and MAT volumes were significantly lower in black than white patients (59
      [twenty-fifth to seventy-fifth percentile 39 to 84] vs 97 [67 to 132] cm(3) and
      44 [27 to 77] vs 87 [52 to 157] cm(3), for both p <0.001). Mean PFT in black
      patients was slightly lower than white patients (17.2 +/- 3.2 vs 18.1 +/- 3.4 mm,
      p <0.01). The relation between race and extent of adipose tissue remained
      significant after adjustment for cardiovascular risk factors. Significant
      correlations were observed between EAT and MAT volumes and calcium score in black
      and white patients (r = 0.19 to 0.26, p <0.01). For both races, the level of
      thoracic fat measurements was higher in present versus absent coronary
      calcification. A greater amount of thoracic fat was found with obstructive CAD
      only in white patients. In conclusion, CT-derived measurements of thoracic fat
      differ between symptomatic black and white patients, suggesting a differential
      relation between thoracic adipose tissue and CAD pathophysiology by race.

PMID- 24315113
TI  - Meta-analysis of gender differences in residual stroke risk and major bleeding in
      patients with nonvalvular atrial fibrillation treated with oral anticoagulants.
AB  - Studies comparing gender-specific outcomes in patients with atrial fibrillation
      (AF) have reported conflicting results. Gender differences in cerebrovascular
      accident/systemic embolism (CVA/SE) or major bleeding outcomes with novel oral
      anticoagulant (NOAC) use are not known. The goal of this analysis was to perform
      a systematic review and meta-analysis evaluating gender differences in residual
      risk of CVA/SE and major bleeding outcomes in patients with nonvalvular AF
      treated with either warfarin or NOAC. Sixty-four randomized studies were
      identified using keywords "gender," "AF," and "CVA." Using the Preferred
      Reporting Items for Systemic Reviews and Meta-analysis method, 6 studies met
      criteria for inclusion in this meta-analysis. CVA/SE and major bleeding outcomes
      were separately analyzed in cohorts receiving warfarin and NOAC agents, comparing
      men with women. Women with AF taking warfarin were at a significantly greater
      residual risk of CVA/SE compared with men (odds ratio 1.279, 95% confidence
      interval 1.111 to 1.473, Z = -3.428, p = 0.001). No gender difference in residual
      risk of CVA/SE was noted in patients with AF receiving NOAC agents (odds ratio
      1.146, 95% confidence interval 0.97 to 1.354, p = 0.109). Major bleeding was less
      frequent in women with AF treated with NOAC. In conclusion, women with AF treated
      with warfarin have a greater residual risk of CVA/SE and an equivalent major
      bleeding risk, whereas those treated with NOAC agents deemed superior to warfarin
      are at equivalent residual risk of CVA/SE and less major bleeding risk compared
      with men. These results suggest an increased net clinical benefit of NOAC agents
      compared with warfarin in treating women with AF.

PMID- 24315114
TI  - Noninvasive cardiac output measurement by inert gas rebreathing in suspected
      pulmonary hypertension.
AB  - The objective of this study was to evaluate inert gas rebreathing (IGR)
      reliability in cardiac output (CO) measurement compared with Fick method and
      thermodilution. IGR is a noninvasive method for CO measurement; CO by IGR is
      calculated as pulmonary blood flow plus intrapulmonary shunt. IGR may be ideal
      for follow-up of patients with pulmonary hypertension (PH), sparing the need of
      repeated invasive right-sided cardiac catheterization. Right-sided cardiac
      catheterization with CO measurement by thermodilution, Fick method, and IGR was
      performed in 125 patients with possible PH by echocardiography. Patients were
      grouped according to right-sided cardiac catheterization-measured mean pulmonary
      and wedge pressures: normal pulmonary arterial pressure (n = 20, mean pulmonary
      arterial pressure = 18 +/- 3 mm Hg, pulmonary capillary wedge pressure = 11 +/- 5
      mm Hg), PH and normal pulmonary capillary wedge pressure (PH-NW, n = 37 mean
      pulmonary arterial pressure = 42 +/- 13 mm Hg, pulmonary capillary wedge pressure
      = 11 +/- 6 mm Hg), and PH and high pulmonary capillary wedge pressure (PH-HW, n =
      68, mean pulmonary arterial pressure = 37 +/- 9 mm Hg, pulmonary capillary wedge
      pressure = 24 +/- 6 mm Hg). Thermodilution and Fick measurements were comparable.
      Fick and IGR agreement was observed in normal pulmonary arterial pressure (CO =
      4.10 +/- 1.14 and 4.08 +/- 0.97 L/min, respectively), whereas IGR overestimated
      Fick in patients with PH-NW and those with PH-HW because of intrapulmonary
      shunting overestimation in hypoxemic patients. When patients with arterial oxygen
      saturation (SO2) <=90% were excluded, IGR and Fick agreement improved in PH-NW
      (CO = 4.90 +/- 1.70 and 4.76 +/- 1.35 L/min, respectively) and PH-HW (CO = 4.05
      +/- 1.04 and 4.10 +/- 1.17 L/min, respectively). In hypoxemic patients, we
      estimated pulmonary shunt as Fick - pulmonary blood flow and calculated shunt as:
      -0.2423 * arterial SO2 + 21.373 L/min. In conclusion, IGR is reliable for CO
      measurement in patients with PH with arterial SO2 >90%. For patients with
      arterial SO2 <=90%, a new formula for shunt calculation is proposed.

PMID- 24315115
TI  - Prognostic value of C-reactive protein as an inflammatory and N-terminal probrain
      natriuretic peptide as a neurohumoral marker in acute heart failure (from the
      Korean Heart Failure registry).
AB  - The neurohumoral and inflammatory pathways are regarded as the main mechanisms
      for the progression of heart failure. We sought to investigate the prognostic
      value of high-sensitivity C-reactive protein (hs-CRP) and N-terminal probrain
      natriuretic peptide (NT-proBNP) by evaluating their relation with 12-month
      mortality rate in this prospective cohort study from 24 academic hospitals in
      Korea. In 1,608 patients with acute heart failure (AHF), the median hs-CRP and NT
      proBNP values were 0.77 mg/dl (interquartile range 0.29 to 2.84) and 4,638 pg/ml
      (interquartile range 1,945 to 10,852), respectively. During the 12-month follow
      up, 213 patients (13.3%) died. The mortality rate increased from the lowest to
      the highest hs-CRP quartiles (Q1 7.4%, Q2 9.5%, Q3 16.9%, Q4 19.3%, p <0.001) and
      NT-proBNP quartiles (Q1 7.0%, Q2 13.4%, Q3 11.6%, Q4 20.4%, p <0.001). After
      adjustment, both hs-CRP (hazard ratio [HR] 1.811, 95% confidence interval [CI]
      1.138 to 2.882) and NT-proBNP (HR 1.971, 95% CI 1.219 to 3.187) were independent
      predictors of 12-month mortality among others. When combining both hs-CRP and NT
      proBNP and stratifying the patients according to their median values, patients
      with elevation of both hs-CRP and NT-proBNP values had 2.4-fold increased hazards
      (HR 2.382, 95% CI 1.509 to 3.761) compared with those without elevation of both
      markers. In Korean patients with AHF, patients with increased levels of both hs
      CRP and NT-proBNP had worse clinical outcomes. The combination of the
      neurohumoral and inflammatory markers may provide a better strategy for risk
      stratification of Asian patients with AHF.

PMID- 24315116
TI  - Usefulness of transient elastography for noninvasive and reliable estimation of
      right-sided filling pressure in heart failure.
AB  - Accurate noninvasive assessment of right atrial pressure (RAP) is important for
      volume management in patients with heart failure (HF). Transient elastography is
      a noninvasive and reliable method to assess liver stiffness (LS). We investigated
      the value of LS for evaluation of RAP in patients with HF without structural
      liver disease. We measured LS using transient elastography (Fibroscan) in 31
      patients undergoing right-sided cardiac catheterization (test group). The
      relation between LS and RAP found in the test group was used to derive the best
      fit model to predict RAP. The applicability of the model was then tested in a
      validation group of 49 additional patients. There was an excellent correlation
      between LS and RAP in the test group (r = 0.95, p <0.0001; RAP = -5.8 + 6.7 * ln
      [LS]). Natural log transformation (ln) of LS provided the regression equation to
      predict RAP. When the equation model derived from the test group was applied to
      the validation group, predicted RAP correlated excellently with actual RAP (r =
      0.90, p <0.0001). The receiver operating characteristic curve analyses in the
      test group showed that LS favorably compared with echocardiography for detecting
      RAP >10 mm Hg (area under the curve 0.958 vs 0.800, respectively, p = 0.047). In
      the validation group, LS with a cut-off value of 10.6 kPa for identifying RAP >10
      mm Hg had a higher sensitivity and accuracy (p = 0.046 and p = 0.049,
      respectively) than echocardiography. In conclusion, LS may offer an accurate
      noninvasive diagnostic method to assess RAP in patients with HF.

PMID- 24315117
TI  - A case of allergic fungal rhinosinusitis due to Ceratocystis adiposa.
AB  - Ceratocystis adiposa known as phytopathogen of conifers has not been recognized
      so far as a human pathogen. Herein, we report for the first time a case of
      allergic fungal rhinosinusitis due to C. adiposa. The fungus was identified by
      sequencing internal transcribed spacer of rDNA and D1/D2 of larger subunit
      region. 

PMID- 24315118
TI  - Molecular cloning, organization, expression and 3D structural analysis of the MHC
      class Ia gene in the whitespotted bamboo shark (Chiloscyllium plagiosum).
AB  - Cartilaginous fishes are the oldest jawed vertebrates, from which the major
      histocompatibility complex (MHC) derived approximately 500 MYA; however, full
      length genomic sequences for MHC genes in these species remain undescribed. This
      lack of basic information about MHC organization in cartilaginous fish is
      hindering investigations into the relationship between MHC polymorphism and
      disease, and leaves a large gap in our understanding of shark MHC evolution.
      Here, we obtained a complete 4887 bp genomic DNA of chplUAA (designated as
      chplUAA) from the whitespotted bamboo shark (Chiloscyllium plagiosum) using long
      PCR. The full-length cDNA sequence was 1385 bp, with a 1029 bp open reading frame
      (ORF) encoding 343 amino acids. Six unique sequences (chplUAA*01-06) were
      detected from 51 sequences from three samples. No more than two sequences were
      found in each individual, suggesting that only one UAA locus was amplified in
      each sample. Phylogenetic analysis supports monophyly of all available shark
      classical class Ia sequences.

PMID- 24315120
TI  - The corrosion of depleted uranium in terrestrial and marine environments.
AB  - Depleted Uranium alloyed with titanium is used in armour penetrating munitions
      that have been fired in a number of conflict zones and testing ranges including
      the UK ranges at Kirkcudbright and Eskmeals. The study presented here evaluates
      the corrosion of DU alloy cylinders in soil on these two UK ranges and in the
      adjacent marine environment of the Solway Firth. The estimated mean initial
      corrosion rates and times for complete corrosion range from 0.13 to 1.9 g cm(-2)
      y(-1) and 2.5-48 years respectively depending on the particular physical and
      geochemical environment. The marine environment at the experimental site was very
      turbulent. This may have caused the scouring of corrosion products and given rise
      to a different geochemical environment from that which could be easily duplicated
      in laboratory experiments. The rate of mass loss was found to vary through time
      in one soil environment and this is hypothesised to be due to pitting increasing
      the surface area, followed by a build up of corrosion products inhibiting further
      corrosion. This indicates that early time measurements of mass loss or corrosion
      rate may be poor indicators of late time corrosion behaviour, potentially giving
      rise to incorrect estimates of time to complete corrosion. The DU alloy placed in
      apparently the same geochemical environment, for the same period of time, can
      experience very different amounts of corrosion and mass loss, indicating that
      even small variations in the corrosion environment can have a significant effect.
      These effects are more significant than other experimental errors and variations
      in initial surface area. 

PMID- 24315119
TI  - The landscape of clinical trials in nephrology: a systematic review of
      Clinicaltrials.gov.
AB  - BACKGROUND: Well-designed trials are of paramount importance in improving the
      delivery of care to patients with kidney disease. However, it remains unknown
      whether contemporary clinical trials within nephrology are of sufficient quality
      and quantity to meet this need. STUDY DESIGN: Systematic review. SETTING &
      POPULATION: Studies registered with ClinicalTrials.gov. SELECTION CRITERIA FOR
      STUDIES: Interventional (ie, nonobservational) studies (both randomized and
      nonrandomized) registered between October 2007 and September 2010 were included
      for analysis. Studies were reviewed independently by physicians and classified by
      clinical specialty. PREDICTOR: Nephrology versus cardiology versus other trials.
      OUTCOMES: Select clinical trial characteristics. RESULTS: Of 40,970 trials
      overall, 1,054 (2.6%) were classified as nephrology. Most nephrology trials were
      for treatment (75.4%) or prevention (15.7%), with very few diagnostic, screening,
      or health services research studies. Most nephrology trials were randomized
      (72.3%). Study designs included 24.9% with a single study group, 64.0% that
      included parallel groups, and 9.4% that were crossover trials. Nephrology trials,
      compared with 2,264 cardiology trials (5.5% overall), were more likely to be
      smaller (64.5% vs 48.0% enrolling<=100 patients), phases 1-2 (29.0% vs 19.7%),
      and unblinded (66.2% vs 53.3%; P<0.05 for all). Nephrology trials also were more
      likely than cardiology trials to include a drug intervention (72.4% vs 41.9%) and
      less likely to report having a data monitoring committee (40.3% vs 48.5%; P<0.05
      for all). Finally, there were few trials funded by the National Institutes of
      Health (NIH; 3.3%, nephrology; 4.2%, cardiology). LIMITATIONS: Does not include
      all trials performed worldwide, and frequent categorization of funding source as
      university may underestimate NIH support. CONCLUSIONS: Critical differences
      remain between clinical trials in nephrology and other specialties. Improving
      care for patients with kidney disease will require a concerted effort to increase
      the scope, quality, and quantity of clinical trials within nephrology.

PMID- 24315121
TI  - Neonatal phototherapy radiometers: current performance characteristics and future
      requirements.
AB  - Hand held radiometers provide a convenient means of monitoring the output of
      neonatal phototherapy treatment devices as part of planned programs of device
      maintenance and output monitoring. It was considered appropriate to determine the
      wavelength and angular response of a selection of such meters and compare their
      indicated values with that derived from spectral analysis of phototherapy light
      sources. This was undertaken using a Bentham DMc150 double grating
      spectroradiometer and a series of 10nm band pass optical filters in the range 400
      640 nm used in conjunction with a fiber optic light source. Specific meters
      investigated included a GE Biliblanket Light Meter II, a NeoBLUE radiometer and a
      Bio-TEK radiometer 74345 device. Comparisons were made of measurements made using
      the hand held meters and the Bentham DMc 150 system for a range of neonatal
      phototherapy treatment devices. The use of such meters is discussed in relation
      to applicable equipment standards and recommendations of intensive phototherapy
      from clinical groups such as the American Academy of Pediatrics and a
      specification for a spectroradiometer based measurement system is proposed.

PMID- 24315123
TI  - The universality of enzymatic rate-temperature dependency.
AB  - Organismal adaptation to extreme temperatures yields enzymes with distinct
      configurational stabilities, including thermophilic and psychrophilic enzymes,
      which are adapted to high and low temperatures, respectively. These enzymes are
      widely assumed to also have unique rate-temperature dependencies. Thermophilic
      enzymes, for example, are considered optimal at high temperatures and effectively
      inactive at low temperatures due to excess rigidity. Surveying published data, we
      find that thermophilic, mesophilic, and psychrophilic enzymes exhibit
      indistinguishable rate-temperature dependencies. Furthermore, given the
      nonenzymatic rate-temperature dependency, all enzymes, regardless of their
      operation temperatures, become >10-fold less powerful catalysts per 25  degrees C
      temperature increase. Among other factors, this loss of rate acceleration may be
      ascribed to thermally induced vibrations compromising the active-site catalytic
      configuration, suggesting that many enzymes are in fact insufficiently rigid.

PMID- 24315124
TI  - Paradoxical relationship between TNF-alpha antagonists and sarcoidosis.

PMID- 24315125
TI  - High productivity purification of immunoglobulin G monoclonal antibodies on
      starch-coated magnetic nanoparticles by steric exclusion of polyethylene glycol.
AB  - We achieved exceptionally high capacity capture of monoclonal IgG by adding 200
      nm starch-coated magnetic particles as nucleation centers, adding polyethylene
      glycol (PEG), then collecting the particle-associated antibody in a magnetic
      field. Experimental data suggest that accretion of IgG begins on particle
      surfaces then continues with fusion of particle-centric accretions up to about
      1mm in a process that closely parallels PEG precipitation. An embedded
      nanoparticle mass of 1.3% of the IgG mass is adequate to enable efficient
      magnetic collection of the associated IgG. Recovery of purified IgG averaged 98%
      up to loads of 78 mg of IgG per mg of particles. Converted to an equivalent
      volume of settled particles, this represents about 58 g IgG per mL of
      nanoparticles, which is roughly 1000 times higher than the average capacity of
      commercial protein A porous particles packed in columns. When applied to cell
      culture harvest clarified by centrifugation and microfiltration, performing the
      nanoparticle technique under physiological conditions permitted only a 10-fold
      reduction of host cell protein (HCP) contamination and IgG recovery less than
      50%. Application of a more capable clarification method and operating the
      nanoparticle method at 0.5-1.0M NaCl supported more than 99% HCP reduction and
      87% IgG recovery. The high salt concentration also dramatically diminished the
      influence of operating pH on selectivity. The nanoparticle step was followed by
      sample application without buffer exchange to a column packed with multimodal
      electropositive-hydrophobic particles that reduced HCP to 2 ppm. Aggregate
      content was reduced from 4.9 to 3.6% at the nanoparticle step, then to less than
      0.05% at the multimodal step. The multimodal step also removed residual PEG.
      Overall IgG recovery was 69%. The ability of the system to achieve purity similar
      to protein A, but dramatically higher productivity than packed columns, suggests
      that the technique could evolve as a credible option for industrial purification
      of monoclonal antibodies.

PMID- 24315126
TI  - Pressure, temperature and density drops along supercritical fluid chromatography
      columns in different thermal environments. III. Mixtures of carbon dioxide and
      methanol as the mobile phase.
AB  - The pressure, temperature and density drops along SFC columns eluted with a
      CO2/methanol mobile phase were measured and compared with theoretical values. For
      columns packed with 3- and 5-MUm particles the pressure and temperature drops
      were measured using a mobile phase of 95% CO2 and 5% methanol at a flow rate of
      5mL/min, at temperatures from 20 to 100 degrees C, and outlet pressures from 80
      to 300bar. The density drop was calculated based on the temperature and pressure
      at the column inlet and outlet. The columns were suspended in a circulating air
      bath, either bare or covered with foam insulation. The experimental measurements
      were compared to theoretical results obtained by numerical simulation. For the
      convective air condition at outlet pressures above 100bar the average difference
      between the experimental and calculated temperature drops and pressure drops were
      0.1 degrees C and 0.7% for the bare 3-MUm column, respectively, and were 0.6
      degrees C and 4.1% for the insulated column. The observed temperature drops for
      the insulated columns are consistent with those predicted by the Joule-Thomson
      coefficients for isenthalpic expansion. The dependence of the temperature and the
      pressure drops on the Joule-Thomson coefficient and kinematic viscosity are
      described for carbon dioxide mobile phases containing up to 20% methanol. 

PMID- 24315127
TI  - Sequential elution liquid chromatography can significantly increase the
      probability of a successful separation by simultaneously increasing the peak
      capacity and reducing the separation disorder.
AB  - This paper demonstrates that sequential elution liquid chromatography (SE-LC), an
      approach in which two or more elution modes are employed in series for the
      separation of two or more groups of compounds, can be used to separate not only
      weak acids (or weak bases) from neutral compounds, but weak acids and weak bases
      from neutral compounds (and each other) by the sequential application of either
      of two types of an extended pH gradient prior to a solvent gradient. It also
      details a comparison, based on peak capacity and separation disorder, of the
      probability of success of this approach with the unimodal elution approach taken
      by conventional column liquid chromatography. For an HPLC peak capacity of 120
      and samples of moderate complexity (e.g., 12 components), the probability of
      success (Rs>=1) increases from 37.9% (HPLC) to 85.8% (SE-LC). Different columns
      were evaluated for their utility for SE-LC using the following criteria: (1) the
      prediction of the elution order of the groups based on the degree of ionization
      of the compounds; and (2) the closeness of the peak shape to the ideal Gaussian
      distribution. The best columns overall were the Zorbax SB-AQ and Waters XBridge
      Shield columns, as they provided both between-class and within-class separations
      of all compounds, as well as the lowest degree of tailing of 4-ethylaniline using
      the pH 2 to pH 8 gradient. 

PMID- 24315128
TI  - [Sociodemographic and medical features of abortion among underage people in
      Guadeloupe (French West Indies)].
AB  - OBJECTIVE: In France, contraception is available for everybody; however, the
      number of abortion does not decrease, especially among young people. The aim of
      our study is to analyze, in the Guadeloupian context, the characteristics of
      underage people who ask for an abortion. METHODS: This retrospective study,
      analyses sociodemographic and medical characteristics of 129 teenagers, who had
      an abortion in 2010 in our abortion center. For 67 of them results of interviews
      with the psychologist were also reported. RESULTS: Preferentially from large
      single parent families, these underage people had a mean age of 15.9 years (+/-
      1.12), 96.1% were born in France, 10.9% had had a previous pregnancy, 67.2% had
      an over 18 partner, 64.4% used contraception before the abortion. Main
      motivations for abortion were continuing studies and young age. Abortion occurs
      after 9 weeks of amenorrhea in 55.1% and 43.3% of underage people reported
      psychological problems linked to the abortion. CONCLUSION: From this profile, our
      study suggests some reflection which could help the fight against unwanted
      pregnancies in this particular population of underage people.

PMID- 24315129
TI  - Maternal attitudes and behaviors regarding feeding practices in elementary school
      aged Latino children: a pilot qualitative study on the impact of the cultural
      role of mothers in the US-Mexican border region of San Diego, California.
AB  - This study aimed to explore the attitudes and behaviors of Latino mothers around
      feeding their children. Using qualitative methods, we conducted four focus groups
      in Spanish with 41 Latino mothers of elementary school-age children in San Diego
      County, CA. Latino mothers' mean age was 41 years; 90% were foreign-born; and 74%
      had a high school education or less. We explored cultural viewpoints around
      feeding and cooking and feeding strategies used. Focus groups were analyzed based
      on a priori and emergent themes. The following themes around feeding emerged:
      feeding attitudes central to the maternal responsibility of having well-fed
      children and feeding behaviors that centered on cooking methods, supportive
      behaviors, and reinforcement strategies for "eating well." These findings
      increase our understanding of the Latino maternal role to feed children and can
      help to inform more culturally appropriate research to effectively address
      nutritional issues and obesity prevention in Latino children. 

PMID- 24315130
TI  - Practice-based evidence of effectiveness in an integrated nutrition and parenting
      education intervention for low-income parents.
AB  - Research identifying associations between parental behaviors and children's food
      and activity choices and weight suggests that the integration of parenting and
      nutrition education holds promise for promoting healthful eating and activity in
      families. However, translational research leading to sustainable interventions
      lags behind. Development and testing of interventions within actual program
      contexts is needed to facilitate translation to full-scale implementation.
      Therefore, the goal of this pilot study was to develop and test an integrated
      nutrition and parenting education intervention for low-income families within the
      Expanded Food and Nutrition Education Program in New York State. During a 21
      month period, low-income parents of 3- to 11-year-olds were recruited through
      usual programmatic channels by nutrition program staff to participate in a series
      of eight workshops delivered to small groups. A validated self-administered
      questionnaire was used to assess behavior change outcomes among 210 parents who
      completed the program. Mean scores improved significantly for most behaviors,
      including adult fruit and vegetable intake; adult and child low-fat dairy and
      soda intake; and child fast-food intake, activity, and screen time (P<0.001).
      Many parents reported eating together with children at program entry, leaving
      little room to improve, but about 20% reported at least a 1-point improvement (on
      a 5-point scale). The most frequent change was reducing how often children ate
      fast food and was reported by >50% of parents. Design and testing through
      practice-based research can facilitate development of interventions that are both
      feasible and likely to improve eating and activity behaviors among low-income
      families.

PMID- 24315131
TI  - ["Surgical" analysis of the new clinical practice guide on compartmental
      syndrome].
AB  - The new published guidelines of compartment syndrome are supposed to be a helpful
      tool in order to make decisions in patients with abdominal hypertension. From a
      surgical perspective of view, an important effort has been made in order to reach
      consensus in different phases in which there is no clear answer in evidence-based
      medicine. It is mandatory the use of a universal classification of open abdomen
      and there are three main concepts that must be observed: make a decompressive
      laparotomy when conservative measures have failed, attempt to closure the abdomen
      as soon as possible and the use of negative-pressure treatments that facilitates
      the management of an open abdomen. Although most of recommendations that have
      been delivered are not high grades, the present guide is an important assistant
      for the management of intra-abdominal hypertension and several lines of
      investigation are opened in order to answer the doubts that have been addressed. 

PMID- 24315132
TI  - [Consensus document on ultrasound training in Intensive Care Medicine. Care
      process, use of the technique and acquisition of professional skills].
AB  - Ultrasound has become an essential tool in assisting critically ill patients. His
      knowledge, use and instruction requires a statement by scientific societies
      involved in its development and implementation. Our aim are to determine the use
      of the technique in intensive care medicine, clinical situations where its
      application is recommended, levels of knowledge, associated responsibility and
      learning process also implement the ultrasound technique as a common tool in all
      intensive care units, similar to the rest of european countries. The SEMICYUC's
      Working Group Cardiac Intensive Care and CPR establishes after literature review
      and scientific evidence, a consensus document which sets out the requirements for
      accreditation in ultrasound applied to the critically ill patient and how to
      acquire the necessary skills. Training and learning requires a structured process
      within the specialty. The SEMICYUC must agree to disclose this document, build
      relationships with other scientific societies and give legal cover through
      accreditation of the training units, training courses and different levels of
      training. 

PMID- 24315133
TI  - [Red cell transfusion and long-term survival in non-complicated heart surgery].
AB  - OBJECTIVE: A study was made to explore the possible association between the
      perioperative transfusion of 1 - 2 red blood cell units and in-hospital
      morbidity, 30-day mortality, and long-term survival in patients undergoing heart
      surgery. DESIGN: A prospective observational study was carried out. SETTING: The
      ICU of a university hospital. PATIENTS: All patients over 17 years of age that
      underwent heart surgery and were admitted to the ICU between November 2002 and
      December 2009 were included. Those patients who did not (n=703) and those who did
      (n=959) receive the perioperative transfusion of 1 - 2 red blood cell units were
      assessed. STUDY ENDPOINTS: The endpoints were the effect of transfusion on both
      hospital morbidity and on 30-day mortality. In addition, all patients discharged
      alive from hospital until 31 December 2011 were subjected to follow-up. The
      association between transfusion and survival was assessed by means of the Kaplan
      Meier method. Cox proportional hazards models were used to assess factors
      associated with long-term survival. RESULTS: The frequency of both cardiac and
      non-cardiac perioperative complications was higher in patients receiving
      transfusion. The 30-day mortality rate was higher in those who received
      transfusion (1% vs 0.1%, P=.02). Preoperative anemia was associated with a more
      intensive use of transfusion. Red blood cell transfusion was not found to be a
      risk factor for long-term mortality (hazar ratio=1.4, 95%CI 0.9-2.1).
      CONCLUSIONS: The perioperative transfusion of 1 - 2 red blood cell units in
      patients undergoing heart surgery increases both hospital morbidity and the 30
      day mortality rate, but does not increase long-term mortality.

PMID- 24315134
TI  - Effects of administration of gonadotropin-releasing hormone at artificial
      insemination on conception rates in dairy cows.
AB  - A controlled trial investigating the effect on conception of administration of
      250 MUg of gonadotropin-releasing hormone (GnRH) at artificial insemination (AI)
      in dairy cows in seasonal or split calving herds was conducted. Time of detection
      of estrus, body condition, extent of estrous expression, treatment, breed, age
      and milk production from the most recent herd test of the current lactation was
      recorded. Cows were tested for pregnancy with fetal aging between 35 and 135 days
      after AI. Sixteen herds provided 2344 spring-calved cows and 3007 inseminations.
      Logistic regression adjusting for clustering at herd level was used to examine
      the effect of treatment for first (2344) and second (579) inseminations
      separately. For first AI, treatment significantly improved conception rate in
      cows with milk protein concentrations of 3.75% or greater and for cows with milk
      protein concentrations between 3.00% and 3.50% and less than 40 days calved;
      increased conception rate from 41.2% to 53.4%. Treatment reduced conception rates
      in cows with milk protein concentrations of 2.75% or less. Treating only cows
      identified as responding positively to treatment (11% of all study cows) was
      estimated to increase first service conception rate in herds from 48.1% to 49.4%.
      There was no significant effect of treatment on conception to second AI, nor any
      significant interactions. These findings indicate that GnRH at AI should be
      limited to the sub-group cows most likely to respond. The positive effect of GnRH
      at AI may be mediated through improved oocyte maturation and/or improved luteal
      function, rather than by reducing AI-to-ovulation intervals.

PMID- 24315135
TI  - Olanzapine and clozapine differently affect sleep in patients with schizophrenia:
      results from a double-blind, polysomnographic study and review of the literature.
AB  - Schizophrenia is associated with impaired sleep continuity. The second generation
      antipsychotics clozapine and olanzapine have been reported to improve sleep
      continuity but also to rarely induce restless legs syndrome (RLS). The aims of
      this randomized double-blind study were to compare the effects of clozapine and
      olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were
      recorded and RLS symptoms were assessed in 30 patients with schizophrenia before
      and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine.
      Treatment with both antipsychotics increased total sleep time, sleep period time
      and sleep efficiency and decreased sleep onset latency. These changes were
      similar in both groups, occurred during the first 2 treatment weeks and were
      sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82%
      (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment
      groups. Sleep architecture was differently affected: clozapine caused a
      significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but
      olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an
      80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No
      patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1
      patient of each group reported at one visit all 4 symptoms, i.e. met the
      diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep
      architecture changed more physiologically with olanzapine. Neither of the
      antipsychotics induced RLS symptoms that were clinically relevant.

PMID- 24315138
TI  - Impact of preoperative marking coils on surgical and pathologic management of
      impalpable lung nodules.
AB  - BACKGROUND: The management of occult lung lesions, particularly subsolid
      opacities, is a new challenge because they are difficult to localize during
      surgery and the number of lesions detected by computed tomography (CT) is
      increasing. METHODS: Between February 2008 and December 2011, preoperative CT
      guided marking with coils was systematically carried out to localize presumed
      impalpable nodules before video-assisted thoracoscopic surgery (VATS). The
      procedure feasibility, reliability, and safety as well as its impact on the
      resection volume and on the pathologic examination strategy were examined.
      RESULTS: This preoperative marking procedure was used for 68 nodules in 60
      consecutive patients. The mean procedural time was 25 minutes/patient and
      complications included minimal asymptomatic pneumothorax (42 cases, 70%) and
      hemorrhagic suffusion (21 patients, 35%). Patients with non-retrieved coils
      during VATS required larger resection volumes (94.88 mm3 vs 20.65 mm3; p=0.008).
      The presence of a coil loop in the pleural space was not statistically associated
      with higher resected lung volume. Primary pulmonary adenocarcinoma was found in
      42 patients (71.2%). Five nodules were associated with atypical adenomatous
      hyperplasia. Pathologic examination was considered to be improved by the presence
      of a coil next to the lesion but not within it. Coil placement modified the
      pathology practices for intraoperative analysis, as tissue sampling in the
      immediate vicinity of the coil was preferred to systematic sampling. CONCLUSIONS:
      Impalpable lung nodules can be safely marked with coils preoperatively to improve
      their surgical and pathologic management.

PMID- 24315137
TI  - Impacts of municipal wastewater oxidative treatments: changes in metal physical
      speciation and bioavailability.
AB  - The environmental repercussions of the discharge of disinfected effluents are
      still poorly understood. This study assessed the impact of ozonation and UV
      oxidative treatment processes on metal forms - particulate, colloidal and
      permeable fractions - and bioavailability in disinfected wastewaters. In addition
      to wastewater analyses, mussels were placed in continuous flow-through aquaria
      and exposed for 4wk to wastewater, then metals in their tissues were analysed in
      parallel with exposure biomarkers. Metal size distribution was affected by
      oxidative processes; results showed that ozonation treatment generally increases
      the permeable fraction of some metals, particularly Cd and Cu, in treated waters,
      whereas UV treatment fosters the formation of permeable Zn. Ozone treatment of
      wastewater generally increased the bioavailability of specific metals. Metal
      bioaccumulation was in most cases significantly higher in mussels exposed to
      ozone-treated effluent compared to the UV treatment: 58%, 32%, 42% and 47%
      higher, respectively, for Ag, Cd, Cr and Cu. Physical metal speciation in these
      wastewaters comparatively measured the permeable fraction of metals to relate
      them to the bioaccumulation results for the exposed mussels. The levels of lipid
      peroxidation were significantly increased in gills but not in the digestive
      gland. The levels of metallothionein in the digestive gland were also
      significantly reduced suggest decreased input of particulate metals. Results of
      bioaccumulation in mussels suggested that metal bioavailability can be modified
      by the different oxidative processes. Despite this disadvantage, ozonation still
      represents a great choice of treatment considering the overall environmental
      benefits. 

PMID- 24315139
TI  - The high prevalence of low-back pain has been highlighted for many years, but
      until recently,awareness of its impact in the population was limited. Preface.

PMID- 24315136
TI  - Mammalian MutY homolog (MYH or MUTYH) protects cells from oxidative DNA damage.
AB  - MutY DNA glycosylase homologs (MYH or MUTYH) reduce G:C to T:A mutations by
      removing misincorporated adenines or 2-hydroxyadenines paired with guanine or 8
      oxo-7,8-dihydroguanine (8-oxo-G). Mutations in the human MYH (hMYH) gene are
      associated with the colorectal cancer predisposition syndrome MYH-associated
      polyposis. To examine the function of MYH in human cells, we regulated MYH gene
      expression by knockdown or overproduction. MYH knockdown human HeLa cells are
      more sensitive to the killing effects of H2O2 than the control cells. In
      addition, hMYH knockdown cells have altered cell morphology, display enhanced
      susceptibility to apoptosis, and have altered DNA signaling activation in
      response to oxidative stress. The cell cycle progression of hMYH knockdown cells
      is also different from that of the control cells following oxidative stress.
      Moreover, hMYH knockdown cells contain higher levels of 8-oxo-G lesions than the
      control cells following H2O2 treatment. Although MYH does not directly remove 8
      oxo-G, MYH may generate favorable substrates for other repair enzymes.
      Overexpression of mouse Myh (mMyh) in human mismatch repair defective HCT15 cells
      makes the cells more resistant to killing and refractory to apoptosis by
      oxidative stress than the cells transfected with vector. In conclusion, MYH is a
      vital DNA repair enzyme that protects cells from oxidative DNA damage and is
      critical for a proper cellular response to DNA damage. 

PMID- 24315140
TI  - Placing the global burden of low back pain in context.
AB  - The latest Global Burden of Disease Study, published at the end of 2012, has
      highlighted the enormous global burden of low back pain. In contrast to the
      previous study, when it was ranked 105 out of 136 conditions, low back pain is
      now the leading cause of disability globally, ahead of 290 other conditions. It
      was estimated to be responsible for 58.2 million years lived with disability in
      1990, increasing to 83 million in 2010. This chapter illustrates the ways that
      the Global Burden of Disease data can be displayed using the data visualisation
      tools specifically designed for this purpose. It also considers how best to
      increase the precision of future global burden of low back pain estimates by
      identifying limitations in the available data and priorities for further
      research. Finally, it discusses what should be done at a policy level to militate
      against the rising burden of this condition.

PMID- 24315141
TI  - Low back pain across the life course.
AB  - Back pain episodes are traditionally regarded as individual events, but this
      model is currently being challenged in favour of treating back pain as a long
      term or lifelong condition. Back pain can be present throughout life, from
      childhood to older age, and evidence is mounting that pain experience is
      maintained over long periods: for example, people with pain continue to have it
      on and off for years, and people without pain do not suddenly develop long-term
      pain. A number of factors predict back pain presence in epidemiological studies,
      and these are often present, and predictive, at different life stages. There are
      also factors present at particular life stages, such as childhood or adolescence,
      which predict back pain in adulthood. However, there are little published data on
      long-term pain patterns or predictors over the life course. Such studies could
      improve our understanding of the development and fluctuations in back pain, and
      therefore influence treatment approaches. 

PMID- 24315142
TI  - Trajectories of low back pain.
AB  - Low back pain is not a self-limiting problem, but rather a recurrent and
      sometimes persistent disorder. To understand the course over time, detailed
      investigation, preferably using repeated measurements over extended periods of
      time, is needed. New knowledge concerning short-term trajectories indicates that
      the low back pain 'episode' is short lived, at least in the primary care setting,
      with most patients improving. Nevertheless, in the long term, low back pain often
      runs a persistent course with around two-thirds of patients estimated to be in
      pain after 12 months. Some individuals never have low back pain, but most have it
      on and off or persistently. Thus, the low back pain 'condition' is usually a
      lifelong experience. However, subgroups of patients with different back pain
      trajectories have been identified and linked to clinical parameters. Further
      investigation is warranted to understand causality, treatment effect and
      prognostic factors and to study the possible association of trajectories with
      pathologies. 

PMID- 24315143
TI  - Is it all about a pain in the back?
AB  - Multisite musculoskeletal pain is common among people suffering from low back
      pain. Although the mechanisms behind co-occurrence of multiple somatic symptoms
      and musculoskeletal pain are still unknown, patients with co-morbidities and co
      occurring musculoskeletal symptoms tend to have worse functional status, a poorer
      prognosis and respond less favourably to treatment. Evidence also suggests that
      the more pain sites a patient reports, the more reduced their physical and mental
      function will be regardless of location of pain. At the same time, evidence
      suggests that strategies for diagnosis and treatment of low back pain and other
      musculoskeletal disorders such as neck pain and lower limb osteoarthritis are
      very similar. In this chapter, we discuss the prevalence, consequences, and
      implications of commonalities between low back pain, pain in other sites and co
      occurring pain. In addition, we propose a conceptual framework for a common
      stepwise approach to the diagnosis and management of back and musculoskeletal
      pain. 

PMID- 24315144
TI  - Psychological factors and treatment opportunities in low back pain.
AB  - A large body of evidence suggests that psychological factors, including emotions,
      beliefs and avoidant behaviours, are linked to poor outcomes in low back pain. At
      the same time, the evidence from trials of psychological interventions suggests
      that they improve outcomes mostly in the short term and against passive controls
      only. These suboptimal results may be due to low competency or fidelity in
      delivery, or inadequate matching of treatment methods with specific patient
      problems. Most importantly, there is insufficient theoretical guidance and
      integration in the design, selection and delivery of methods that precisely
      target known process of pathology. We identify several new directions for
      research and opportunities to improve the impact of psychological interventions
      and to change clinical practice. These include better ways to conceptualise and
      deliver reassurance at early stages of back pain, utilising models such as the
      psychological flexibility model to guide treatment development, and essentially
      extend the fear-avoidance model. 

PMID- 24315145
TI  - Effects of workplace, family and cultural influences on low back pain: what
      opportunities exist to address social factors in general consultations?
AB  - Social factors are widely acknowledged in behavioural models of pain and pain
      management, but incorporating these factors into general medical consultations
      for low back pain (LBP) can be challenging. While there is no compelling evidence
      that social factors contribute to LBP onset, these factors have been shown to
      influence functional limitation and disability, especially the effects of
      organisational support in the workplace, spousal support, family conflict and
      social disadvantage. A number of barriers exist to address such social factors in
      routine medical encounters for LBP, but there is emerging evidence that improving
      social and organisational support may be an effective strategy to reduce the
      negative lifestyle consequences of LBP. For clinicians to address these factors
      in LBP treatment requires a clearer psychosocial framework in assessment and
      screening, more individualised problem-solving efforts, more patient-centred
      interventions involving family, peers and workplace supports and a less
      biomechanical and diagnostic approach. 

PMID- 24315146
TI  - Stratified models of care.
AB  - Stratified care for back pain involves targeting treatment to subgroups of
      patients based on their key characteristics such as prognostic factors, likely
      response to treatment and underlying mechanisms. It aims to tailor therapeutic
      decisions in ways that maximise treatment benefit, reduce harm and increase
      health-care efficiency by offering the right treatment to the right patient at
      the right time. From being called the 'Holy Grail' of back pain research over a
      decade ago, stratified care is becoming the zeitgeist in research and clinical
      practice. In this chapter, we introduce and evaluate the quality and underpinning
      evidence for three examples of stratified care for back pain to highlight their
      general principles, research design issues and clinical practice implications. We
      include consideration of their merits for implementation in practice. We conclude
      with a set of remaining, key research questions. 

PMID- 24315148
TI  - Evidence for surgery in degenerative lumbar spine disorders.
AB  - We aimed to evaluate the available evidence on the effectiveness of surgical
      interventions for a number of conditions resulting in low back pain (LBP) or
      spine-related irradiating leg pain. We searched the Cochrane databases and PubMed
      up to June 2013. We included systematic reviews and randomised controlled trials
      (RCTs) on degenerative disc disease (DDD), herniated disc, spondylolisthesis and
      spinal stenosis due to degenerative osteoarthritis. We included comparisons
      between surgery and conservative care and between different techniques. The
      quality of the systematic reviews was evaluated using assessment of multiple
      systematic reviews (AMSTAR). Twenty systematic reviews were included which
      covered the following diagnoses: disc herniation (n = 9), spondylolisthesis (n =
      2), spinal stenosis (n = 3), DDD (n = 4) and combinations (n = 2). For most of
      the comparisons, no significant and/or clinically relevant differences between
      interventions were identified. In general, surgery is only indicated for relief
      of leg pain in clear indications such as disc herniation, spondylolisthesis or
      spinal stenosis.

PMID- 24315147
TI  - Long-term use of opioids for complex chronic pain.
AB  - Increased opioid prescribing for back pain and other chronic musculoskeletal pain
      conditions has been accompanied by dramatic increases in prescription-opioid
      addiction and fatal overdose. Opioid-related risks appear to increase with dose.
      Although short-term randomised trials of opioids for chronic pain have found
      modest analgesic benefits (a one-third reduction in pain intensity on average),
      the long-term safety and effectiveness of opioids for chronic musculoskeletal
      pain remains unknown. Given the lack of large, long-term randomised trials,
      recent epidemiologic data suggest the need for caution when considering long-term
      use of opioids to manage chronic musculoskeletal pain, particularly at higher
      dosage levels. Principles for achieving more selective and cautious use of
      opioids for chronic musculoskeletal pain are proposed. 

PMID- 24315149
TI  - Why and how back pain interventions work: what can we do to find out?
AB  - Mediation analysis is a useful research method that potentially allows
      identification of the mechanisms through which treatments affect patient
      outcomes. This chapter reviews the theoretical framework, research designs and
      statistical approaches used in mediation analysis. It describes what can be
      learnt from previous mediation research, much of which has investigated mediating
      factors of psychosocial interventions in other health conditions. It also
      summarises the few treatment-mediation studies of psychosocial interventions
      conducted in back pain. This chapter shows that there is emerging evidence about
      the role of some psychological factors as potential treatment mediators, such as
      self-efficacy and catastrophising. Mediation analysis can equally be applied to
      non-psychological factors. Pre-planned and appropriately conducted mediation
      analysis in adequately powered clinical trials would be a step forward in
      understanding treatment effects in back pain and improving patient management. 

PMID- 24315150
TI  - Low back pain research--future directions.
AB  - Low back pain is a challenge for clinicians and researchers, due to the large
      variability in clinical presentation, lack of consensus regarding diagnostic
      criteria or clinical classification; wide variation in course and prognosis, and
      limited success in identifying effective treatments. However, increasing research
      efforts has generated an expanding body of evidence on the epidemiology,
      prognosis and treatment of back pain. This paper presents four key developments
      in research and clinical practice, and describes how these can influence the
      future direction of back pain research: (1) the increasing awareness of the
      impact of low back pain on population health; (2) new approaches to describing
      and investigating course and prognosis of back pain; (3) the need to better
      understand the bio-psycho-social mechanisms or pathways that explain impact and
      long-term outcomes in order to inform intervention research; and (4) the
      potential for stratified models of care to improve patient outcomes and
      efficiency of care for back pain. 

PMID- 24315151
TI  - Blood flow characteristics in the ascending aorta after aortic valve replacement-
      a pilot study using 4D-flow MRI.
AB  - BACKGROUND: Aortic remodeling after aortic valve replacement (AVR) might be
      influenced by the postoperative blood flow pattern in the ascending aorta. This
      pilot study used flow-sensitive four-dimensional magnetic resonance imaging (4D
      flow) to describe ascending aortic flow characteristics after various types of
      AVR. METHODS: 4D-flow was acquired in 38 AVR patients (n=9 mechanical, n=8
      stentless bioprosthesis, n=14 stented bioprosthesis, n=7 autograft) and 9 healthy
      controls. Analysis included grading of vortex and helix flow (0-3 point scale),
      assessment of systolic flow eccentricity (1-3 point scale), and quantification of
      the segmental distribution of peak systolic wall shear stress (WSS(peak)) in the
      ascending aorta. RESULTS: Compared to controls, mechanical prostheses showed the
      most distinct vorticity (2.7+/-0.5 vs. 0.7+/-0.7; p<0.001), while stented
      bioprostheses exhibited most distinct helicity (2.6+/-0.7 vs. 1.6+/-0.5;
      p=0.002). Instead of a physiologic central flow, all stented, stentless and
      mechanical prostheses showed eccentric flow jets mainly directed towards the
      right-anterior aortic wall. Stented and stentless prostheses showed an asymmetric
      distribution of WSS(peak) along the aortic circumference, with significantly
      increased local WSS(peak) where the flow jet impinged on the aortic wall. Local
      WSS(peak) was higher in stented (1.4+/-0.7 N/m(2)) and stentless (1.3+/-0.7
      N/m(2)) compared to autografts (0.6+/-0.2 N/m(2); p=0.005 and p=0.008) and
      controls (0.7+/-0.1 N/m(2); p=0.017 and p=0.027). Autografts exhibited lower
      absolute WSS(peak) than controls (0.4+/-0.1 N/m(2) vs. 0.7+/-0.2 N/m(2);
      p=0.003). CONCLUSIONS: Flow characteristics in the ascending aorta after AVR are
      different from native aortic valves and differ between various types of AVR.

PMID- 24315152
TI  - Does the amount of atrial mass reduction improve clinical outcomes after
      radiofrequency catheter ablation for long-standing persistent atrial
      fibrillation? Comparison between linear ablation and defragmentation.
AB  - BACKGROUND: Although a large isolated surface area of the left atrium (LA) may
      improve the success rate of catheter ablation (CA) for paroxysmal atrial
      fibrillation (AF), little is known about the relation between clinical outcomes
      and the amount of atrial mass reduction (AMR: ratio of total isolated and ablated
      areas to LA surface area) in different ablation strategies for patients with long
      standing persistent AF (L-PeAF). METHODS: We randomly assigned 119 consecutive L
      PeAF patients to adjunctive linear ablation (n=60) or complex fractionated atrial
      electrogram (CFAE)-guided ablation (n=59) after circumferential antral pulmonary
      vein isolation (PVI). Linear lesions included roof and anterior lines with
      conduction block. LA defragmentation was performed with an automated CFAE
      detection algorithm. Cavotricuspid isthmus block was performed in all patients.
      Creatine kinase-MB (CK-MB) and troponin-T levels were measured 1 day post-CA.
      RESULTS: CK-MB and troponin-T levels were higher, ablation time was longer, and
      AMR was greater in the CFAE-guided ablation group than in the linear ablation
      group. AF termination during CA was more frequently observed in the linear
      ablation group than in the CFAE-guided ablation group (P=0.031). Twelve months
      after a single procedure, recurrence occurred in 16 (26.7%) patients with linear
      ablation and 27 (45.8%) patients with CFAE-guided ablation (P=0.023). On
      multivariate analysis, LA volume and ablation method were the only independent
      risk factors for arrhythmia recurrence. CONCLUSION: Conduction block through
      linear lines+PVI was an efficient ablation strategy for L-PeAF, whereas the AMR
      amount did not influence clinical outcomes.

PMID- 24315153
TI  - Reservoir and excess pressures predict cardiovascular events in high-risk
      patients.
AB  - BACKGROUND: Analysis of the arterial pressure curve plays an increasing role in
      cardiovascular risk stratification. Measures of wave reflection and aortic
      stiffness have been identified as independent predictors of risk. Their
      determination is usually based on wave propagation models of the circulation.
      Another modeling approach relies on modified Windkessel models, where pressure
      curves can be divided into reservoir and excess pressure. Little is known of
      their prognostic value. METHODS AND RESULTS: The aim of this study is to evaluate
      the predictive value of parameters gained from reservoir theory applied to aortic
      pressure curves in a cohort of high-risk patients. Furthermore the relation of
      these parameters to those from wave separation analysis is investigated. Central
      pressure curves from 674 patients with preserved ejection fraction, measured by
      radial tonometry and a validated transfer function, were analyzed. A high
      correlation between the amplitudes of backward traveling pressure waves and
      reservoir pressures was found (R=0.97). Various parameters calculated from the
      reservoir and excess pressure waveforms predicted cardiovascular events in
      univariate Cox proportional hazards modeling. In a multivariate model including
      several other risk factors such as brachial blood pressure, the amplitude of
      reservoir pressure remained a significant predictor (HR=1.37 per SD, p=0.016).
      CONCLUSIONS: Based on very different models, parameters from reservoir theory and
      wave separation analysis are closely related and can predict cardiovascular
      events to a similar extent. Although Windkessel models cannot describe all of the
      physiological properties of the arterial system, they can be useful to analyze
      its behavior and to predict cardiovascular events.

PMID- 24315154
TI  - A survey of central venous catheter practices in Australian and New Zealand
      tertiary neonatal units.
AB  - BACKGROUND: Infection is the most common problem with central venous catheters
      (CVCs) in neonates. There are two published guidelines, including the Centers for
      Disease Control and Prevention (CDC), for the prevention of intravascular
      catheter-related infection that describes evidence-based practice to reduce
      nosocomial infection. OBJECTIVE: Our aims were to survey current medical and
      nursing management of central venous catheters in tertiary neonatal intensive
      care units in Australia and New Zealand and to compare with the CDC evidence
      based practice guideline. METHODS: A cross sectional survey was performed across
      27 Australian and New Zealand neonatal units in September 2012. Two web-based
      questionnaires were distributed, one to medical directors related to the
      insertion of CVCs while CVC "maintenance" surveys were sent to nurse unit
      managers. RESULTS: Seventy percent (19/27) medical management and 59% (16/27) on
      nursing management surveys were completed. In all neonatal intensive care units
      (NICUs) there were guidelines for CVC maintenance and for 18 out of 19 there were
      guidelines for insertion. In the seven units using femoral lines, three had a
      guideline on insertion and four for maintenance. CVC insertion was restricted to
      credentialed staff in 57.9% of neonatal units. Only 26.5% used full maximal
      sterile barriers for insertion. Skin disinfection practices widely varied.
      Dressing use and dressing change regimens were standardised; all using a semi
      permeable dressing. Duration of cleaning time of the access point varied
      significantly; however, the majority used a chlorhexidine with alcohol solution
      (68.8%). Line and fluid changes varied from daily to 96 h. The majority used
      sterile gloves and a sterile dressing pack to access the CVC (68.8%). In the
      majority of NICUs stopcocks were used (62.5%) with a needle-less access point
      attached (87.5%). In less than 50% of NICUs education was provided on insertion
      and maintenance. CONCLUSION: There is diversity of current practices and some
      aspects vary from the CDC guideline. There is a need to review NICU current
      practices to align with evidence based guidelines. The introduction of a common
      guideline may reduce variations in practice.

PMID- 24315155
TI  - A liver schwannoma observed in a female Sprague-Dawley rat treated with MNU.
AB  - BACKGROUND: Schwannoma is a tumor of the nervous system composed by Schwann
      cells. It can occur naturally in several tissues of the body in both humans and
      animals. Diaphragmatic hernia can be congenital or acquired and is defined as a
      protrusion of abdominal viscera into the thoracic cavity. MATERIALS AND METHODS:
      The animal was a female rat from an experiment of mammary tumor chemically
      induced. It was injected with N-methyl-N-nitrosourea (MNU) and died spontaneously
      at 22 weeks of age. RESULTS: The animal had a diaphragmatic hernia and a
      hemorrhagic and multicystic mass in the liver herniated lobule. Microscopically
      the liver displayed a well circumscribed mass that was a tumor with hemorrhagic
      areas, necrosis and Antoni A and Antoni B patterns. It also displayed occasional
      positivity to vimentin and diffuse positivity to S-100 and NSE. CONCLUSION: The
      tumor was a schwannoma with the origin in the Glisson's capsule.

PMID- 24315157
TI  - Medical genetic inspirations for anticancer drug repurposing.

PMID- 24315156
TI  - Vaccine efficacy of transcutaneous immunization with amyloid beta using a
      dissolving microneedle array in a mouse model of Alzheimer's disease.
AB  - Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade
      hypothesis has recently attracted attention for treating AD. Injectable
      immunization using amyloid beta peptide (Abeta) comprising 1-42 amino-acid
      residues (Abeta1-42) as antigens showed therapeutic efficacy in mice; however,
      the clinical trial of this injected Abeta1-42 vaccine was stopped due to the
      incidence of meningoencephalitis caused by excess activation of Th1 cells
      infiltrating the brain as a serious adverse reaction. Because recent studies have
      suggested that transcutaneous immunization (TCI) is likely to elicit Th2-dominant
      immune responses, TCI is expected to be effective in treating AD without inducing
      adverse reactions. Previously reported TCI procedures employed complicated and
      impractical vaccination procedures; therefore, a simple, easy-to-use, and novel
      TCI approach needs to be established. In this study, we investigated the vaccine
      efficacy of an Abeta1-42-containing TCI using our novel dissolving microneedle
      array (MicroHyala; MH) against AD. MH-based TCI induced anti-Abeta1-42 immune
      responses by simple and low-invasive application of Abeta1-42-containing MH to
      the skin. Unfortunately, this TCI system resulted in little significant
      improvement in cognitive function and Th2-dominant immune responses, suggesting
      the need for further modification. 

PMID- 24315158
TI  - How can we explain physician accuracy in assessing patient distress? A multilevel
      analysis in patients with advanced cancer.
AB  - OBJECTIVE: To examine the determinants of the accuracy with which physicians
      assess metastatic cancer patient distress, also referred to as their empathic
      accuracy (EA). Hypothesized determinants were physician empathic attitude, self
      efficacy in empathic skills, physician-perceived rapport with the patient,
      patient distress and patient expressive suppression. METHODS: Twenty-eight
      physicians assessed their patients' distress level on the distress thermometer,
      while patients (N=201) independently rated their distress level on the same tool.
      EA was the difference between both scores in absolute value. Hypothesized
      determinants were assessed using self-reported questionnaires. Multilevel
      analyses were carried out. RESULTS: Little of the variance in EA was explained by
      physician variables. EA was higher with higher levels of patient distress.
      Physician-perceived quality of rapport was positively associated with EA.
      However, for highly distressed patients, good rapport was associated with lower
      EA. Patient expressive suppression was also related to lower EA. CONCLUSION: This
      study adds to the understanding of EA in oncological settings, particularly in
      challenging the common assumption that EA depends largely on physician
      characteristics or that better rapport would always favor higher EA. PRACTICE
      IMPLICATIONS: Physicians should ask patients for feedback regarding their
      emotions. In parallel, patients should be prompted to express their concerns.

PMID- 24315159
TI  - 'What they're not telling you': a new scale to measure grandparents' information
      needs when their grandchild has cancer.
AB  - OBJECTIVE: To determine the information needs and preferences of grandparents of
      children with cancer, to identify clinically useful predictors of high
      information need, and to develop the first validated scale to assess
      grandparents' information needs regarding their grandchild's cancer. METHODS:
      Grandparents of children with cancer completed a questionnaire, including a newly
      developed instrument to measure information needs. RESULTS: Eighty-seven
      grandparents participated (mean age 65.02 years, range 46-81, 31% male).
      Grandparents' information needs were high, especially among young and paternal
      grandparents. Grandparents' greatest need was for information pertaining to their
      grandchild's chance of survival (81.6% reported "high need"), possible
      consequences of the child's cancer (81.6%), and phases of their treatment
      (72.4%). Ninety-three percent endorsed the development of a grandparents'
      booklet, distributed at diagnosis and available online. CONCLUSIONS: Grandparents
      of children with cancer desire more information for their own reassurance, to
      reduce their reliance on 'second-hand' information from their grandchild's
      parents and to improve the support they provide their families. Grandparents
      strongly endorse the development of grandparent-targeted educational resources.
      PRACTICE IMPLICATIONS: Administration of this short, 15-item questionnaire can
      help staff identify the information needs of grandparents. Findings will inform
      the development of evidence-based resources for this important (but oft
      neglected) population.

PMID- 24315161
TI  - Improving the health of older Indigenous Canadians.

PMID- 24315162
TI  - The global crisis of severe acute malnutrition in children.

PMID- 24315160
TI  - The role of coping in depression treatment utilization for VA primary care
      patients.
AB  - OBJECTIVE: To examine the impact of Veterans' coping strategies on mental health
      treatment engagement following a positive screen for depression. METHODS: A mixed
      methods observational study using a mailed survey and semi-structured interviews.
      Sample included 271 Veterans who screened positive for depression during a
      primary care visit at one of three VA medical centers and had not received a
      diagnosis of depression or prescribed antidepressants 12 months prior to
      screening. A subsample of 23 Veterans was interviewed. RESULTS: Logistic
      regression models showed that Veterans who reported more instrumental support and
      active coping were more likely to receive depression or other mental health
      treatment within three months of their positive depression screen. Those who
      reported emotional support or self-distraction as coping strategies were less
      likely to receive any treatment in the same time frame. Qualitative analyses
      revealed that how Veterans use these and other coping strategies can impact
      treatment engagement in a variety of ways. CONCLUSIONS: The relationship between
      Veterans' use of coping strategies and treatment engagement for depression may
      not be readily apparent without in-depth exploration. PRACTICE IMPLICATIONS: In
      VA primary care clinics, nurse care managers and behavioral health providers
      should explore how Veterans' methods of coping may impact treatment engagement.

PMID- 24315163
TI  - Violence against women in Syria.

PMID- 24315164
TI  - Reinvesting in health post-2015.

PMID- 24315165
TI  - Sex and percutaneous coronary intervention.

PMID- 24315167
TI  - Dean Jamison: putting economics at the heart of global health.

PMID- 24315168
TI  - Efficacy of antipsychotic drugs for schizophrenia.

PMID- 24315169
TI  - Efficacy of antipsychotic drugs for schizophrenia.

PMID- 24315170
TI  - Efficacy of antipsychotic drugs for schizophrenia - Authors' reply.

PMID- 24315171
TI  - Surgical clinical trials--need for international collaboration.

PMID- 24315172
TI  - Surgical clinical trials--need for quantity and quality.

PMID- 24315173
TI  - Care for patients with grave alcohol use disorders.

PMID- 24315174
TI  - Surgical clinical trials--need for international collaboration.

PMID- 24315175
TI  - Mental illness and crime in Brazil.

PMID- 24315176
TI  - Care for patients with grave alcohol use disorders - Authors' reply.

PMID- 24315177
TI  - A gloomy future for medical students in China.

PMID- 24315178
TI  - Fatal hyperammonaemia caused by Mycoplasma hominis.

PMID- 24315179
TI  - The role of rainwater-borne hydrogen peroxide in the release of arsenic from
      arsenopyrite.
AB  - A microcosm experiment was conducted to examine the effects of hydrogen peroxide
      (at a concentration range of 5-50 MUM) on the release of arsenic from the
      dissolution of arsenopyrite, a dominant arsenic-bearing mineral occurring in
      natural environments. This was to simulate the reaction between rainwater-borne
      hydrogen peroxide and arsenopyrite grains exposed on the land surfaces during
      rainfall events. The results showed that the release of arsenic from arsenopyrite
      was enhanced by the H2O2 at this concentration range. It was also evident that
      H2O2 played an indirect role in the transformation of arsenite into arsenate in
      the solutions, which might affect the fate of the liberated arsenic species due
      to the formation of FeAsO4 precipitates. The preliminary study sheds some light
      on the possible role of rainwater-borne H2O2 in the weathering of arsenopyrite,
      which could complicate the geochemical processes governing the release, transport
      and fate of arsenopyrite-derived arsenic in natural environments. This provides a
      rationale for conducting additional laboratory-based investigations to obtain
      further insights into the chemical mechanisms and kinetics, and the subsequent
      field-scale study to validate the research findings.

PMID- 24315180
TI  - Behavior of nanoscale titanium dioxide in laboratory wastewater treatment plants
      according to OECD 303 A.
AB  - The fate assessment of nanomaterials in municipal sewage treatment plants (STP)
      is a crucial step for their environmental risk assessment and may be assessed by
      monitoring full scale STP, dosage to medium scale pilot STP or by laboratory
      testing. For regulatory purposes preferably standardised test protocols such as
      the OECD guidelines for testing of chemicals should be used. However, these test
      protocols have not yet been specifically designed for nanoparticles. Therefore,
      the fate and behavior of a TiO2 nanomaterial (P25, average hydrodynamic diameter
      <250 nm) was investigated in laboratory sewage treatment plants according to the
      OECD Guideline for the Testing of Chemicals 303 A. It is concluded that this
      guideline is applicable for the testing of nanomaterials if modifications
      regarding the dosage, nitrifying conditions, and a characterisation of the
      nanoparticles in the effluent are applied. A compilation of the cumulative mass
      balance by comparison of the total dosage added with the amount in the outflow
      and in the activated sludge is recommended. In this study, the majority of the
      TiO2 nanomaterial (>95%) was retained in the sewage sludge and only 3-4% was
      found in the effluent. No effect of the TiO2 nanomaterials on the biodegradation
      or nitrification was observed.

PMID- 24315181
TI  - Particle size, charge and colloidal stability of humic acids coprecipitated with
      Ferrihydrite.
AB  - Humic acids (HA) have a colloidal character whose size and negative charge are
      strictly dependent on surface functional groups. They are able to complex large
      amount of poorly ordered iron (hydr)oxides in soil as a function of pH and other
      environmental conditions. Accordingly, with the present study we intend to assess
      the colloidal properties of Fe(II) coprecipitated with humic acids (HA) and their
      effect on Fe hydroxide crystallinity under abiotic oxidation and order of
      addition of both Fe(II) and HA. TEM, XRD and DRS experiments showed that Fe-HA
      consisted of Ferrihydrite with important structural variations. DLS data of Fe-HA
      at acidic pH showed a bimodal size distribution, while at very low pH a slow
      aggregation process was observed. Electrophoretic zeta-potential measurements
      revealed a negative surface charge for Fe-HA macromolecules, providing a strong
      electrostatic barrier against aggregation. Under alkaline conditions HA chains
      swelled, which resulted in an enhanced stabilization of the colloid particles.
      The increasing of zeta potential and size of the Fe-HA macromolecules, reflects a
      linear dependence of both with pH. The increase in the size and negative charge
      of the Fe-HA precipitate seems to be more affected by the ionization of the
      phenolic acid groups, than by the carboxylic acid groups. The main cause of
      negative charge generation of Fe/HA is due to increased dissociation of phenolic
      groups in more expanded structure. The increased net negative surface potential
      induced by coprecipitation with Ferrihydrite and the correspondent changes in
      configuration of the HA could trigger the inter-particle aggregation with the
      formation of new negative surface. The Fe-HA coprecipitation can reduce
      electrosteric repulsive forces, which in turn may inhibit the aggregation process
      at different pH. Therefore, coprecipitation of Ferrihydrite would be expected to
      play an important role in the carbon stabilization and persistence not only in
      organic soils, but also in waters containing dissolved organic matter. 

PMID- 24315182
TI  - Preliminary ecotoxicity assessment of new generation alternative fuels in
      seawater.
AB  - The United States Navy (USN) is currently demonstrating the viability of
      environmentally sustainable alternative fuels to power its fleet comprised of
      aircraft and ships. As with any fuel used in a maritime setting, there is
      potential for introduction into the environment through transport, storage, and
      spills. However, while alternative fuels are often presumed to be eco-friendly
      relative to conventional petroleum-based fuels, their environmental fate and
      effects on marine environments are essentially unknown. Here, standard laboratory
      based toxicity experiments were conducted for two alternative fuels, jet fuel
      derived from Camelina sativa (wild flax) seeds (HRJ5) and diesel fuel derived
      from algae (HRD76), and two conventional counterparts, jet fuel (JP5) and ship
      diesel (F76). Initial toxicity tests performed on water-accommodated fractions
      (WAF) from neat fuels partitioned into seawater, using four standard marine
      species in acute and chronic/sublethal tests, indicate that the alternative fuels
      are significantly less toxic to marine organisms. 

PMID- 24315183
TI  - Use of an occlusion balloon in transbronchial lung cryobiopsy.

PMID- 24315184
TI  - Self-citation: should it be penalized?

PMID- 24315185
TI  - Oligo-recurrence from a lung adenocarcinoma. Usefulness of resection.

PMID- 24315186
TI  - Missed opportunities in antipneumococcal vaccination. Can something more be done
      for prevention?
AB  - INTRODUCTION: Vaccination is the most effective measure in the prevention of
      invasive pneumococcal disease (IPD). High-risk patients immunized during medical
      visits would benefit from the vaccine. OBJECTIVES: To describe the IPD cases. To
      assess the most prevalent causative serotypes and to evaluate the missed
      opportunities for vaccination. METHODS: This is a descriptive retrospective study
      of the incidence of IPD cases in Elche during 5 years. It was reviewed the
      vaccination status and the visits to specialized care prior to disease. It was
      also calculated the vaccine effectiveness with the 23-valent pneumococcal vaccine
      in our population. RESULTS: Between 2007 and 2011 were notified 181 of IPD, the
      most frequent medical conditions were pneumonia and sepsis, with a mortality rate
      of 12%. 80% of the causative serotypes are included in the vaccine. More than the
      half of the cases had at least one of the risk factor for indicating the
      vaccination. This percentage decreases by 6.2% in cases below 65 years of age
      with any risk factor. CONCLUSIONS: After 10 years of introducing the vaccine into
      the adult immunization schedule the coverage it is still low among the patients
      with risk factors. In our study, 75% of the cases were not vaccinated. Taking in
      count the vaccine effectiveness for preventing IPD, among the patients attended
      at the hospital by the specialist prior their IPD, it could have been prevented
      in the best assumption (85% vaccine effectiveness) 60 IPD cases.

PMID- 24315187
TI  - Disease at the wildlife-livestock interface: acaricide use on domestic cattle
      does not prevent transmission of a tick-borne pathogen with multiple hosts.
AB  - Several prominent and economically important diseases of livestock in East Africa
      are caused by multi-host pathogens that also infect wildlife species, but
      management strategies are generally livestock focused and models of these
      diseases tend to ignore the role of wildlife. We investigate the dynamics of a
      multi-host tick-borne disease in order to assess the efficacy of tick control
      from an ecological perspective. We examined the efficacy of a widespread measure
      of tick control and developed a model to explore how changes in the population of
      ticks due to control measures on cattle impact dynamics of Theileria parva
      infection in a system with two primary host species, cattle and Cape buffalo
      (Syncerus caffer). We show that the frequency of acaricide application has a
      significant impact on the tick population both on the host and in the
      environment, which can greatly reduce the pathogen load in cattle. We also
      demonstrate that reducing the tick population through cattle-related control
      measures is not sufficient to diminish disease transmission in buffalo. Our
      results suggest that under current control strategies, which target ticks on
      cattle only, T. parva is likely to remain a significant problem in East Africa,
      and require the continued use of acaricides, which has significant economic and
      ecological consequences. 

PMID- 24315188
TI  - Acaricidal properties of two extracts from Guiera senegalensis J.F. Gmel.
      (Combrataceae) against Hyalomma anatolicum (Acari: Ixodidae).
AB  - Laboratory test were carried out on eggs, larvae, nymphs and adults of Hyalomma
      anatolicum to determine the acaricidal activities of petroleum ether (PE) and
      crude ethanolic extracts (EE) from the leaves of Guiera senegalensis J.F. Gmel.
      (Combrataceae) using immersion method. Stock solutions, of 300 mg/ml (30%) of the
      each two extract, were prepared. Six two-fold serial dilutions each with three
      replicates were used. Both extracts, at the highest concentration 150 mg/ml
      (15%), induced 100% failure of hatching of the treated eggs. The concentrations
      of PE and EE that induced 50% inhibition of the hatchability (IC50) were 1.71 and
      0.508%, respectively. In the larval immersion test (LIT), EE at 15% concentration
      caused complete mortality while the same concentration of PE resulted in 96%
      mortality. The mortalities increased with concentrations. There was a correlation
      between the mortalities and increased concentrations, the values of the linear
      correlation coefficient (r) for PE and EE were 0.93 and 0.79, and The LC50 and
      LC99 were 2.08 and 14.09, and 0.787 and 11.054, respectively. At the
      concentrations of 3.75%, 7.5% and 15%, PE inhibited the molting of the nymphs by
      40, 55 and 65%, respectively, while EE induced 46.49, 64.3 and 71.4% inhibition,
      respectively. The effectiveness of the treatment against unfed adult females was
      assessed by measuring the feeding performance and egg production using adult
      immersion test (AIT). Although, there was no mortality in unfed adults, PE and EE
      inhibited feeding and egg-laying of the survived females by 35-100% and 6.16
      100%, respectively. Our results indicated that G. senegalensis is a promising
      biocontrol candidate as an acaricidal agent against H. anatolicum.

PMID- 24315189
TI  - Synthesis of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazines that have
      antibacterial activity and also inhibit inorganic pyrophosphatase.
AB  - Inorganic pyrophosphatases are potential targets for the development of novel
      antibacterial agents. A pyrophosphatase-coupled high-throughput screening assay
      intended to detect o-succinyl benzoic acid coenzyme A (OSB CoA) synthetase
      inhibitors led to the unexpected discovery of a new series of novel inorganic
      pyrophosphatase inhibitors. Lead optimization studies resulted in a series of 3
      (3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazine derivatives that were prepared by
      an efficient synthetic pathway. One of the tetracyclic triazine analogues 22h
      displayed promising antibiotic activity against a wide variety of drug-resistant
      Staphylococcus aureus strains, as well as activity versus Mycobacterium
      tuberculosis and Bacillus anthracis, at a concentration that was not cytotoxic to
      mammalian cells. 

PMID- 24315190
TI  - Probing the human estrogen receptor-alpha binding requirements for phenolic mono-
      and di-hydroxyl compounds: a combined synthesis, binding and docking study.
AB  - Various estrogen analogs were synthesized and tested for binding to human ERalpha
      using a fluorescence polarization displacement assay. Binding affinity and
      orientation were also predicted using docking calculations. Docking was able to
      accurately predict relative binding affinity and orientation for estradiol, but
      only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di
      hydroxyl compounds sometimes bind in two orientations, which are flipped in terms
      of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were
      predicted to bind with their aliphatic hydroxyl group interacting with His524 in
      ERalpha. One nonsteroid-based dihdroxyl compound was 1000-fold specific for
      ERbeta over ERalpha, and was also 25-fold specific for agonist ERbeta versus
      antagonist activity. Docking predictions suggest this specificity may be due to
      interaction of the aliphatic hydroxyl with His475 in the agonist form of ERbeta,
      versus with Thr299 in the antagonist form. But, the presence of this aliphatic
      hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic)
      compounds bind ERalpha with high affinity, via hydroxyl hydrogen bonding
      interactions with the ERalpha Arg394/Glu353/water triad, and van der Waals
      interactions with the rest of the molecule. 

PMID- 24315191
TI  - Discovery of novel antitumor dibenzocyclooctatetraene derivatives and related
      biphenyls as potent inhibitors of NF-kappaB signaling pathway.
AB  - Several dibenzocyclooctatetraene derivatives (5-7) and related biphenyls (8-11)
      were designed, synthesized, and evaluated for inhibition of cancer cell growth
      and the NF-kappaB signaling pathway. Compound 5a, a dibenzocyclooctatetraene
      succinimide, was discovered as a potent inhibitor of the NF-kappaB signaling
      pathway with significant antitumor activity against several human tumor cell
      lines (GI50 1.38-1.45 MUM) and was more potent than paclitaxel against the drug
      resistant KBvin cell line. Compound 5a also inhibited LPS-induced NF-kappaB
      activation in RAW264.7 cells with an IC50 value of 0.52 MUM, prevented IkappaB
      alpha degradation and p65 nuclear translocation, and suppressed LPS-induced NO
      production in a dose-dependent manner. The antitumor data in cellular assays
      indicated that relative positions and types of substituents on the
      dibenzocyclooctatetraene or acyclic biphenyl as well as torsional angles between
      the two phenyls are of primary importance to antitumor activity.

PMID- 24315192
TI  - Biphenyl derivatives incorporating urea unit as novel VEGFR-2 inhibitors: design,
      synthesis and biological evaluation.
AB  - A series of novel biphenyl urea derivates were synthesized and investigated for
      their potential to inhibit vascular endothelial growth factor receptor-2 (VEGFR
      2). In particular, A7, B3 and B4 displayed significant enzymatic inhibitory
      activities, with IC50 values of 4.06, 4.55 and 5.26 nM. Compound A7 exhibited
      potent antiproliferative activity on several cell lines. SAR study suggested that
      the introduction of methyl at ortho-position of the biphenyl urea and tertiary
      amine moiety could improve VEGFR-2 inhibitory activity and antitumor effects.
      Molecular docking indicated that the urea moiety formed four hydrogen bonds with
      DFG residue. These biphenyl ureas could serve as promising lead compounds for
      further optimization.

PMID- 24315193
TI  - Synthesis and evaluation of (-)- and (+)-[11C]galanthamine as PET tracers for
      cerebral acetylcholinesterase imaging.
AB  - Improved radiopharmaceuticals for imaging cerebral acetylcholinesterase (AChE)
      are needed for the diagnosis of Alzheimer's disease (AD). Thus, (11)C-labeled (-)
      galanthamine and its enantiomers were synthesized as novel agents for imaging the
      localization and activity of AChE by positron emission tomography (PET). C-11 was
      incorporated into (-)- and (+)-[(11)C]galanthamine by N-methylation of
      norgalanthamines with [(11)C]methyl triflate. Simple accumulation of (11)C in the
      brain was measured in an in vivo biodistribution study using mice, whilst
      donepezil was used as a blocking agent in analogous in vivo blocking studies. In
      vitro autoradiography of rat brain tissue was performed to investigate the
      distribution of (-)-[(11)C]galanthamine, and confirmed the results of PET studies
      in mice. The radiochemical yields of N-methylation of (-)- and (+)
      norgalanthamines were 13.7% and 14.4%, respectively. The highest level of
      accumulation of (11)C in the brains of mice was observed at 10 min after
      administration (2.1% ID/g). Intravenous pretreatment with donepezil resulted in a
      30% decrease in accumulation of (-)-[(11)C]galanthamine in the striatum; however,
      levels in the cerebellum were unchanged. In contrast, use of (+)
      [(11)C]galanthamine led to accumulation of radioactivity in the striatum equal to
      that in the cerebellum, and these levels were unaffected by pretreatment with
      donepezil. In in vitro autoradiography of regional radioactive signals of brain
      sections showed that pretreatment with either (-)-galanthamine or donepezil
      blocked the binding of (-)-[(11)C]galanthamine to the striatum, while sagittal
      PET imaging revealed accumulation of (-)-[(11)C]galanthamine in the brain. These
      results indicate that (-)-[(11)C]galanthamine showed specific binding to AChE,
      whereas (+)-[(11)C]-galanthamine accumulated in brain tissue by non-specific
      binding. Thus, optically pure (-)-[(11)C]galanthamine could be a useful PET
      tracer for imaging cerebral AChE.

PMID- 24315194
TI  - Flexible and biomimetic analogs of triple uptake inhibitor 4-((((3S,6S)-6
      benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol: Synthesis, biological
      characterization, and development of a pharmacophore model.
AB  - In this study we have generated a pharmacophore model of triple uptake inhibitor
      compounds based on novel asymmetric pyran derivatives and the newly developed
      asymmetric furan derivatives. The model revealed features important for
      inhibitors to exhibit a balanced activity against dopamine transporter (DAT),
      serotonin transporter (SERT), and norepinephrine transporter (NET). In
      particular, a 'folded' conformation was found common to the active pyran
      compounds in the training set and was crucial to triple uptake inhibitory
      activity. Furthermore, the distances between the benzhydryl moiety and the N
      benzyl group as well as the orientation of the secondary nitrogen were also
      important for TUI activity. We have validated our findings by synthesizing and
      testing novel asymmetric pyran analogs. The present work has also resulted in the
      discovery of a new series of asymmetric tetrahydrofuran derivatives as novel
      TUIs. Lead compounds 41 and 42 exhibited moderate TUI activity. Interestingly,
      the highest TUI activity by lead tetrahydrofuran compounds for example, 41 and
      42, was exhibited in a stereochemical preference similar to pyran TUI for
      example, D-161. 

PMID- 24315196
TI  - Maternal stress and depressive symptoms associated with quality of developmental
      care in 25 Italian Neonatal Intensive Care Units: a cross sectional observational
      study.
AB  - BACKGROUND: Parents of very preterm infants are at great risk for experiencing
      stress and depression. The so called developmental care oriented approach used in
      Neonatal Intensive Care Units have beneficial effects for parents. However the
      actual level of developmental care may vary among units and little is known about
      how the routine adoption of developmental care affects maternal stress and
      depression. OBJECTIVES: To investigate the extent to which level of quality of
      developmental care routinely carried out in 25 tertiary Neonatal Intensive Care
      Units across Italy affects maternal stress and depression. PARTICIPANTS: 178
      mothers of healthy very preterm infants with gestational age <=29wk and/or birth
      weight <=1500g and without documented neurologic pathologies were recruited
      consecutively. 180 full-term mothers were recruited as the control group.
      METHODS: To distinguish the quality of developmental care level, each unit was
      assessed using a specifically developed questionnaire. We compared negative
      emotional states of mothers by splitting the 25 Neonatal Intensive Care Units
      into units with high-care and low-care based on median splits for two main care
      factors: (1) The Infant Centered Care index (consisting of measures of parent
      involvement, including ability to room in, frequency and duration of kangaroo
      care and nursing interventions aimed at decreasing infant energy expenditure and
      promoting autonomic stability). (2) The Infant Pain Management index (consisting
      of measures to decrease painful experiences including pharmacologic and nursing
      care practices). Maternal stress was assessed by the Parental Stressor Scale:
      Neonatal Intensive Care Unit questionnaire. Maternal depressive symptomatology
      was assessed by the Edinburgh Postnatal Depression Scale questionnaire. RESULTS:
      Preterm mothers from low-care units in the Infant Pain Management reported higher
      scores in their perception of stress associated with behavior and appearance of
      the infant than mothers from high-care units (p=0.05). Preterm mothers from high
      care units in the Infant Pain Management reported a depressive symptomatology
      score average similar to that reported by full-term mothers. No significant
      Infant Centered Care effect was found both for maternal stress and depression.
      CONCLUSIONS: The findings suggest that implementing more practices useful to
      reduce infants' painful experience can mitigate the stress and depressive
      symptomatology of the preterm mothers.

PMID- 24315195
TI  - Strategies for lead discovery: application of footprint similarity targeting
      HIVgp41.
AB  - A highly-conserved binding pocket on HIVgp41 is an important target for
      development of anti-viral inhibitors. Holden et al. (Bioorg. Med. Chem.
      Lett.2012, 22, 3011) recently reported 7 experimentally-verified leads identified
      through a computational screen to the gp41 pocket in conjunction with a new DOCK
      scoring method (termed FPS scoring) developed in our laboratory. The method
      employs molecular footprints based on per-residue van der Waals interactions,
      electrostatic interactions, or the sum. In this work, we critically examine the
      gp41 screening results, prioritized using different scoring methods, in terms of
      two main criteria: (1) ligand pose properties which include footprint and energy
      score decompositions, MW, number of rotatable bonds, ligand efficiency, formal
      charge, and volume overlap, and (2) ligand pose stability which includes
      footprint stability (changes in footprint overlap) and rmsd stability (changes in
      geometry). Relative to standard DOCK scoring, pose property analyses demonstrate
      how FPS scoring can be used to identify ligands that mimic a known reference
      (derived here from the native gp41 substrate), while pose stability analyses
      demonstrate how FPS scoring can be used to enrich for compounds with greater
      overall stability during molecular dynamics (MD) simulations. Compellingly, of
      the 115 compounds tested experimentally, the 7 active compounds, as a group, more
      closely mimic the footprints made by the reference and show greater MD stability
      compared to the inactive group. Extensive studies using 116 protein-ligand
      complexes as controls reveal that ligands in their crystallographic binding pose
      also maintain higher FPS scores and smaller rmsds than do accompanying decoys,
      confirming that native poses are indeed 'stable' under the same conditions and
      that monitoring FPS variability during compound prioritization is likely to be
      beneficial. Overall, the results suggest the new scoring method will complement
      current virtual screening approaches for both the identification (FPS-ranking)
      and prioritization (FPS-stability) of target-compatible molecules in a
      quantitative and logical way. 

PMID- 24315197
TI  - Botulinum toxin-responsive ear myoclonus following otitis externa.

PMID- 24315198
TI  - Clinical and neuroimaging features of patient with early-onset Parkinson's
      disease with dementia carrying SNCA p.G51D mutation.

PMID- 24315200
TI  - Is nicotine still the bad guy? Summary of the effects of smoking on patients with
      head and neck cancer in the postoperative period and the uses of nicotine
      replacement therapy in these patients.
AB  - Smoking has long been implicated in the development and progression of numerous
      postoperative complications. The cause is largely thought to be the presence of
      reactive oxygen species (ROS) in cigarette smoke, which attenuates inflammation
      and affects neutrophil function. Wound healing is further compromised by
      deficiencies in vitamins C and E, which result from a higher vitamin turnover
      secondary to the oxidative stress produced by smoking. However, studies recently
      have found that the effects of nicotine may benefit healing if used in isolation.
      We summarise the effects that smoking and abstaining from smoking can have on
      inflammation and wound healing, and describe the possible benefits that nicotine
      replacement and antioxidant supplements can give. 

PMID- 24315199
TI  - Novel mutations c.[5121_5122insAG]+[6859C>T] of the SPG11 gene associated with
      cerebellum hypometabolism in a Chinese case of hereditary spastic paraplegia with
      thin corpus callosum.
AB  - Hereditary spastic paraplegia (HSP) is a very heterogeneous disease, both
      genetically and clinically. To date, approximately 52 loci and 31 genes have been
      reported to be involved in the causality of HSP. The pattern of inheritance of
      the disease can be autosomal dominant, autosomal recessive, or X-linked
      recessive. Autosomal recessive HSP with thin corpus callosum (ARHSP-TCC) is one
      form of this disease, and a recessive gene, SPG11, is responsible for 41-77% of
      all ARHSP-TCC cases. SPG11 encodes the protein SPATACSIN, which is most
      prominently expressed in the cerebellum. However, little is known about its
      function. Despite diverse clinical presentations, diffuse hypometabolism in the
      cerebellum has not been reported previously. We have identified an HSP-TCC
      patient that presented with prominent intellectual disability rather than
      spasticity. (18)Fluorodeoxyglucose positron emission tomography/computed
      tomography ((18)FDG-PET/CT) examination showed diffuse hypometabolism in both
      cerebella. Mutation screening of the SPG11 gene using Sanger sequencing
      identified the novel compound heterozygous mutation c.[5121_5122insAG]+[6859C>T]
      (p.[I1708RfsX2]+[Q2287X]) in the patient. The mother bears the c.5121_5122insAG
      mutation, which results in a frameshift and is predicted to truncate the 735
      amino acids from the C-terminus, and the father carries the c.6859C>T mutation,
      which terminates the 157 amino acids from the C-terminus. Therefore, these
      mutations may result in the loss of function of wild-type SPATACSIN. Our results
      suggest that SPATACSIN may be involved in cerebella metabolism, and the novel
      mutations provide more data for the mutational spectrum of this gene, which will
      aid in the development of quick and accurate genetic diagnostic tools for this
      disease.

PMID- 24315201
TI  - Jejunal free flap for reconstruction of pharyngeal defects in patients with head
      and neck cancer-the Birmingham experience.
AB  - We retrospectively audited operative complications, success of flaps, and speech
      and swallowing outcomes in patients with head and neck cancer who had
      reconstruction with jejunal free tissue transfer to the pharynx. A total of 104
      patients had jejunal free flaps between 1987 and 2009 at University Hospital,
      Birmingham. Management was by a multidisciplinary team, and the same vascular
      surgeon did all the anastomoses. We investigated the relations between patients,
      operative factors, and postoperative complications, and noted the ischaemic time
      of the flaps and coexisting conditions of the patients. Outcomes measured
      included initial and final survival rates of flaps, donor and recipient site
      complications, and speech and swallowing outcomes on discharge and up to 2 years
      postoperatively. Of the 104 patients, 14 (13%) had initial flap complications but
      overall flap survival was 97%. A total of 11 (11%) patients developed a fistula
      at a mean of 15 days postoperatively and 11 (11%) had minor donor site
      complications. A total of 95 (91%) were able to resume oral diet on discharge. Of
      the 44 who were followed up on discharge, 32 (73%) were able to maintain oral
      intake at 2 years and 31 (70%) could use their voice in everyday situations. The
      jejunal free flap enables the tumour to be removed, and reconstruction and
      restoration of function to be done in a single operation using tissue that is
      versatile. The operation is associated with low morbidity at the donor and
      recipient sites, and results in good speech and swallowing outcomes. The flap can
      also be used to reconstruct pharyngolaryngeal defects. 

PMID- 24315202
TI  - [Statement by SemFYC on the access to scientific information by general
      practioners].

PMID- 24315203
TI  - [Free flap reconstruction in the head and neck. Indications, technical aspects
      and outcomes].
AB  - INTRODUCTION AND OBJECTIVES: The use of microvascular free flaps (MFF) has become
      a common method of head and neck reconstruction because of its high success rates
      and better functional results. We report our experience in reconstructing complex
      defects with MFF. METHODS: We analysed a series of 246 patients that underwent
      reconstruction using MFF in our Department from 1991 to 2013. RESULTS: There were
      259 interventions performed in 246 patients. The most common reason for surgery
      was tumour recurrence (46%), followed by primary tumour resection (25%). The
      hypopharynx (52%) and the craniofacial region (22%) were the most frequently
      reconstructed sites. The free flaps most commonly used were the radial forearm
      free flap (41%) and the anterolateral thigh free flap (35%). Overall success and
      complication rates of 92% and 20% respectively were reported. CONCLUSIONS: The
      microvascular free flap is a reliable and useful tool for reconstructing complex
      head and neck defects and continues to be the reconstructive modality of choice
      for these defects.

PMID- 24315205
TI  - Photoreduction of graphene oxide with polyoxometalate clusters and its enhanced
      saturable absorption.
AB  - We investigated the photocatalytic abilities of three Keggin-type polyoxometalate
      (POM) clusters, H3PW12O40 (PW), H4SiW12O40 (SiW), and H3PMo12O40 (PMo) to reduce
      graphene oxide (GO) under UV-irradiation in water. UV-vis absorption and X-ray
      photoelectron spectroscopy were performed and show that PW and SiW can
      photoreduce GO effectively, in contrast to PMo. We conclude that the LUMO levels
      of POMs should be located energetically above the work function of GO to enable
      electron transfer from POM to GO. We also investigated the saturable absorption
      of GO and reduced GO by means of z-scan experiments at 532 nm. The POM-assisted
      photoreduction of GO can greatly enhance the saturable absorber properties of GO,
      which appears useful for modelocking in ultrafast laser systems.

PMID- 24315204
TI  - TLR4 and NLRP3 inflammasome activation in monocytes by N-propionyl
      cysteaminylphenol-maleimide-dextran (NPCMD).
AB  - BACKGROUND: N-propionyl cysteaminylphenol-maleimide-dextran (NPCMD) is a toxic
      tyrosinase substrate developed to treat melanoma. OBJECTIVE: We investigated the
      effect of NPCMD on innate immune responses in monocytes. METHODS: CD14+ monocytes
      and a monocytic cell line, THP-1, were stimulated with NPCMD in vitro. Cytokines
      in the culture supernatants were determined by ELISA and flow cytometry. RESULTS:
      NPCMD stimulated CD14+ monocytes and THP-1 cells to secrete TNFalpha, IL-6 and IL
      8, but not IL-10 or IL-12. TNFalpha secretion from THP-1 cells stimulated with
      NPCMD was inhibited by addition of an anti-TLR4 mAb in culture. Moreover, NPCMD
      stimulated production of pro-IL-1beta in CD14+ monocytes and monocytic cell line
      THP-1 cells and activated the NLRP3-inflammasome, resulting in production of
      mature IL-1beta. Use of ASC and NLRP3-deficient THP-1 cell lines established
      involvement of the NLRP3 inflammasome in an IL-1beta secretion in treatment with
      NPCMD. Inhibition of IL-1beta secretion by an endocytosis inhibitor, cytochalasin
      B, and a lysosomal enzyme cathepsin B inhibitor, CA-074 Me, suggested the
      involvement of lysosomal rupture and leakage of cathepsin B into the cytosol in
      NLRP3 activation by NPCMD. CONCLUSION: The immunopotentiating effect of NPCMD
      mediated by TLR4 and NLRP3 inflammasome activation could be useful for eliciting
      effective adaptive immune responses against melanoma and other tumors.

PMID- 24315206
TI  - Comprehensive profile of GATA binding protein 3 immunohistochemical expression in
      primary and metastatic renal neoplasms.
AB  - Transcription factor GATA binding protein 3 (GATA3) has been suggested as a
      marker of urothelial carcinoma of the bladder and upper urinary tract. Its
      expression in primary and metastatic renal tumors has not been fully determined.
      We evaluated GATA3 expression in 47 oncocytomas, 196 primary renal cell
      carcinomas (RCCs) (71 clear cell, 53 papillary, 21 Xp11.2, 33 chromophobe RCCs,
      and 18 collecting duct carcinomas [CDC]), and 43 unrelated metastatic RCCs (41
      clear cell and 2 Xp11.2 RCC). GATA3 nuclear expression was evaluated in tissue
      microarrays built from archival tissues using immunohistochemistry. Intensity (0
      to 3+) and extent (percentage) of expression were assessed. Several cutoff values
      (>0%, >5%, and >10%) were evaluated to indicate GATA3 positivity. Among
      oncocytomas, 9 (19%) of 47 had some degree of nuclear GATA3 expression with
      median extent of 0% (0%-100%). When using either 5% or 10% cutoff values, 5 (11%)
      of 47 oncocytomas were positive. In primary RCCs, 6 (3%) of 196 had some degree
      of nuclear expression with a median extent of 0% (0%-100%). When using either 5%
      or 10% cutoff values, 2 cases remained positive (1%) (Xp11.2 and CDC). All
      metastatic RCCs were negative. We found an overall lack of GATA3 expression in
      primary and metastatic RCCs. GATA3 is expressed in a minority of oncocytomas,
      Xp11.2-RCC, and CDC. Given GATA3 positivity in upper urinary tract urothelial
      carcinoma, our findings support a role for GATA3 in the differential diagnosis of
      primary renal masses and a utility in the interrogation of metastatic tumors of
      unknown primary in the presence of a renal mass. 

PMID- 24315208
TI  - Lung clearance index: evidence for use in clinical trials in cystic fibrosis.
AB  - The ECFS-CTN Standardisation Committee has undertaken this review of lung
      clearance index as part of the group's work on evaluation of clinical endpoints
      with regard to their use in multicentre clinical trials in CF. The aims were 1)
      to review the literature on reliability, validity and responsiveness of LCI in
      patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3)
      to gain consensus on answers to key questions regarding the promotion of LCI to
      surrogate endpoint status. It was concluded that LCI has an attractive
      feasibility and clinimetric properties profile and is particularly indicated for
      multicentre trials in young children with CF and patients with early or mild CF
      lung disease. This is the first article to collate the literature in this manner
      and support the use of LCI in clinical trials in CF. 

PMID- 24315209
TI  - Phenotypic and molecular characteristics of an Aeromonas hydrophila strain
      isolated from the River Nile.
AB  - Aeromonas hydrophila, an inhabitant of aquatic ecosystems found in most parts of
      the world, has considerable virulence potential. The polymerase chain reaction
      technique was used to assay for the presence of five virulence factor genes:
      haemolytic toxins aerA and ahh1, elastase ahyB, the enterotoxin act, and the
      polar flagella flaA/flaB in the A. hydrophila strain isolated from the River
      Nile. Drug screening showed high levels of resistance to beta-lactam antibiotics
      and tetracycline. Slime production was determined by the Congo red agar plate
      test. The isolate produced two restriction enzymes named AehI and AehII which are
      isoschizomers of XhoI and StuI respectively. The complete nucleotide sequence of
      the cryptic plasmid pAhy2.5 (2524 bp) from this strain was determined. Sequence
      analysis revealed the presence of two open reading frames (ORFs) encoding
      putative proteins. The protein coded by ORF1 is homologous with Rep proteins of
      plasmids belonging to the pC194 family, which are known to replicate by the
      rolling-circle mechanism. The putative double-strand origin of replication and a
      region with palindromic sequences that could function as a single-strand origin
      were detected in pAhy2.5.

PMID- 24315207
TI  - Endothelium as a gatekeeper of fatty acid transport.
AB  - The endothelium transcends all clinical disciplines and is crucial to the
      function of every organ system. A critical, but poorly understood, role of the
      endothelium is its ability to control the transport of energy supply according to
      organ needs. Fatty acids (FAs) in particular represent a key energy source that
      is utilized by a number of tissues, but utilization must be tightly regulated to
      avoid potentially deleterious consequences of excess accumulation, including
      insulin resistance. Recent studies have identified important endothelial
      signaling mechanisms, involving vascular endothelial growth factor-B, peroxisome
      proliferator-activated receptor-gamma, and apelin, that mediate endothelial
      regulation of FA transport. In this review, we discuss the mechanisms by which
      these signaling pathways regulate this key endothelial function. 

PMID- 24315210
TI  - Does a rhizospheric microorganism enhance K+ availability in agricultural soils?
AB  - The potassium solubilizing microorganisms (KSMs) are a rhizospheric microorganism
      which solubilizes the insoluble potassium (K) to soluble forms of K for plant
      growth and yield. K-solubilization is carried out by a large number of
      saprophytic bacteria (Bacillus mucilaginosus, Bacillus edaphicus, Bacillus
      circulans, Acidothiobacillus ferrooxidans, Paenibacillus spp.) and fungal strains
      (Aspergillus spp. and Aspergillus terreus). Major amounts of K containing
      minerals (muscovite, orthoclase, biotite, feldspar, illite, mica) are present in
      the soil as a fixed form which is not directly taken up by the plant. Nowadays
      most of the farmers use injudicious application of chemical fertilizers for
      achieving maximum productivity. However, the KSMs are most important
      microorganisms for solubilizing of fixed form of K in soil system. The KSMs are
      an indigenous rhizospheric microorganism which shows effective interaction
      between soil and plant systems. The main mechanism of KSMs is acidolysis,
      chelation, exchange reactions, complexolysis and production of organic acid.
      According to literature, currently negligible use of potassium fertilizer as a
      chemical form has been recorded in agriculture for enhancing crop yield. Most of
      the farmers use only nitrogen and phosphorus and not use the K fertilizer due to
      unawareness so that the problem of K deficiency occurs in rhizospheric soils. The
      K fertilizer is also costly as compared to other chemical fertilizers. Therefore,
      the efficient KSMs should be applied for solubilization of a fixed form of K to
      an available form of K in the soils. This available K can be easily taken up by
      the plant for growth and development. Our aim of this review is to elaborate on
      the studies of indigenous K-solubilizing microbes to develop efficient microbial
      consortia for solubilization of K in soil which enhances the plant growth and
      yield of crops. This review highlights the future need for research on potassium
      (K) in agriculture. 

PMID- 24315211
TI  - YouTube as an information source for pediatric adenotonsillectomy and ear tube
      surgery.
AB  - OBJECTIVES: Assess the overall quality of information on adenotonsillectomy and
      ear tube surgery presented on YouTube (www.youtube.com) from the perspective of a
      parent or patient searching for information on surgery. METHODS: The YouTube
      website was systematically searched on select dates with a formal search strategy
      to identify videos pertaining to pediatric adenotonsillectomy and ear tube
      surgery. Only videos with at least 5 (ear tube surgery) or 10
      (adenotonsillectomy) views per day were included. Each video was viewed and
      scored by two independent scorers. Videos were categorized by goal and scored for
      video/audio quality, accuracy, comprehensiveness, and procedure-specific content.
      STUDY DESIGN: Cross-sectional study. SETTING: Public domain website. RESULTS:
      Fifty-five videos were scored for adenotonsillectomy and forty-seven for ear tube
      surgery. The most common category was educational (65.3%) followed by testimonial
      (28.4%), and news program (9.8%). Testimonials were more common for
      adenotonsillectomy than ear tube surgery (41.8% vs. 12.8%, p=0.001). Testimonials
      had a significantly lower mean accuracy (2.23 vs. 2.62, p=0.02),
      comprehensiveness (1.71 vs. 2.22, p=0.007), and TA specific content (0.64 vs.
      1.69, p=0.001) score than educational type videos. Only six videos (5.9%)
      received high scores in both video/audio quality and accuracy/comprehensiveness
      of content. There was no significant association between the accuracy and
      comprehensive score and views, posted "likes", posted "dislikes", and
      likes/dislikes ratio. There was an association between "likes" and mean video
      quality (Spearman's rho=0.262, p=0.008). CONCLUSION: Parents/patients searching
      YouTube for information on pediatric adenotonsillectomy and ear tube surgery will
      generally encounter low quality information with testimonials being common but of
      significantly lower quality. Viewer perceived quality ("likes") did not correlate
      to formally scored content quality.

PMID- 24315212
TI  - Use of tympanometry in general practice in Denmark.
AB  - OBJECTIVES: Otitis media has been a serious disease and can be that even today.
      The diagnosis of otitis media is often difficult. Pneumatic otoscopy,
      otomicroscopy, and tympanometry can improve the diagnostic quality by indication
      of fluid in the middle ear and thereby improve the quality of treatment. The aim
      of this ongoing study is to analyze the use of tympanometry in Denmark after
      reimbursement for doing tympanometry (November 2006) when clinically indicated.
      Our research questions were: How many clinics were using tympanometry? How
      frequent was it used? Is the use increasing? Has the number of GPs in the clinic
      any relation to the use of tympanometry? METHOD: We used information in The
      Danish National Health Service in three Regions to analyze the use of
      tympanometry in general practice during the years 2007-2009. The coverage of the
      GPs is 100% in the regions. RESULTS: The three regions counted about half of
      Danish population. In 2009 the material was 902 different clinics with more than
      1700 GPs. In 2007 55% of the clinics did tympanometry, in 2009 the figure was
      60%. In the clinics doing tympanometry the median value was 28 tympanometries per
      year (inter-quartile range 13-53) per GP. The variation in the use of
      tympanometry was surprisingly high, from none or a few per GP per year to a
      maximum of more than 500 tympanometric examinations per GP a year. This huge
      variation has to be discussed. DISCUSSION: Many answers can be given. Some of the
      explanation was problems in doing correct tympanometry, and problems understand
      the clinical implications of curves and the figures.

PMID- 24315213
TI  - Persistent oro-nasal fistula after primary cleft palate repair: minimizing the
      rate via a standardized protocol.
AB  - OBJECTIVES: Multiple methods are described for cleft palate repair. Similarly, a
      wide range of postoperative oro-nasal fistula rates are described, depending on
      technique and series examined. We describe long-term outcomes and fistula rates
      for primary cleft palate repair for a single surgeon using a standardized
      protocol. Furlow palatoplasty was used for clefts limited to the soft palate, and
      two-flap palatoplasty was used for clefts involving both the hard and soft
      palate. METHODS: Retrospective review of prospectively gathered data. RESULTS:
      Eighty-two patients underwent cleft palate repair within the study period.
      Average age at time of repair was 1.69 years (range 0.47-12.1 years), 19 patients
      had cleft palate as a part of a known genetic syndrome, and male:female ratio was
      1.05:1. Overall fistula rate requiring repair was 5.5%, and fistula development
      was not significantly associated with type of cleft repair or use of AlloDerm in
      the repair. CONCLUSIONS: A very low rate of oro-nasal fistula and good
      postoperative outcomes were achieved utilizing this protocol for cleft palate
      repair. It is effective both in isolated cleft palate, as well as in more
      complicated syndromic patients. It is possible that significant associations
      between repair technique and fistula rate exist that were not elucidated in this
      study as a result of the small number of oro-nasal fistulas.

PMID- 24315214
TI  - Pediatric laryngeal neurofibroma: case report and review of the literature.
AB  - Presentation of a case of pediatric laryngeal neurofibroma (LNF) and review of
      the world literature. Comprehensive review of the world literature using Pubmed
      and Google scholar. Pediatric LNF was identified in 62 cases reported in the
      world literature. The most common presenting symptom is stridor and the most
      common location of the tumor in the larynx is the aryepiglottic fold. Recent
      reports demonstrate increased utilization of endoscopic resection with reduced
      need for tracheostomy. Pediatric LNF is a rare disorder. Review of the world
      literature since 1940 suggests a recent trend away from aggressive open resection
      and toward more conservative endoscopic resection with excellent functional
      results. 

PMID- 24315215
TI  - Parental perception of speech and tongue mobility in three-year olds after
      neonatal frenotomy.
AB  - OBJECTIVES: The goal of this study was to evaluate parental speech outcomes and
      tongue mobility in children with ankyloglossia who underwent frenotomy by an
      otolaryngologist during the neonatal period. STUDY DESIGN: Cohort study and
      retrospective telephone survey. STUDY SETTING: University Hospital. SUBJECTS AND
      METHODS: Neonates previously diagnosed with congenital ankyloglossia were
      separated into Surgical Intervention (N=71) and No Surgical Intervention (N=15)
      Groups. A Control Group (N=18) of patients was identified from the hospital
      medical record database, which were not diagnosed with congenital ankyloglossia.
      A survey provided by a certified speech pathologist utilized a Likert scale to
      assess speech perception and tongue mobility by parental listeners. The
      questionnaire also analyzed oral motor activities and the medical professionals
      that identified the ankyloglossia shortly after birth. Statistical analyses were
      performed with the Wilcoxon Rank Sum Test and Fischer's Exact Test in order to
      determine an effect size=1. RESULTS: There was significantly improved speech
      outcomes designated by parents in the Surgical Intervention Group when compared
      to the No Surgical Intervention Group [p<0.0001, p<0.0001], respectively.
      Furthermore, parents designated no difference in speech outcomes between the
      Surgical Intervention Group when analyzed against the Control Group [p=0.3781,
      p<0.2499], respectively. CONCLUSIONS: There was a statistically significant
      improvement in speech outcomes and tongue mobility in children who underwent
      frenotomy compared to individuals who declined the operation. As a result of the
      data presented within this study, there appears to be a long-term benefit beyond
      feeding when frenotomy is performed in newborns with ankyloglossia.

PMID- 24315216
TI  - Gradenigo's syndrome: is fusobacterium different? Two cases and review of the
      literature.
AB  - Gradenigo's syndrome is a rare but life threatening complication of acute otitis
      media (AOM), which includes a classic triad of otitis media, deep facial pain and
      ipsilateral abducens nerve paralysis. The incidence of Fusobacterium necrophorum
      infections has increased in recent years. We describe two cases of Gradenigo's
      syndrome caused by F. necrophorum. Additional four cases were identified in a
      review of the literature. Gradenigo's syndrome as well as other neurologic
      complications should be considered in cases of complicated acute otitis media. F.
      necrophorum should be empirically treated while awaiting culture results.

PMID- 24315217
TI  - Computational proteomics in the post-identification era.

PMID- 24315219
TI  - [The twenty-first century will be religious or it will not be].

PMID- 24315218
TI  - Brief motivational enhancement intervention to prevent or reduce postpartum
      alcohol use: a single-blinded, randomized controlled effectiveness trial.
AB  - AIMS: The aim of this study is to assess the effect of brief motivational
      enhancement intervention postpartum alcohol use. DESIGN: This study is a single
      blinded, randomized controlled effectiveness trial in which pregnant women were
      assigned to receive usual care or up to 5 face-to-face brief motivational
      enhancement sessions lasting 10-30 minutes each and occurring at study
      enrollment, 4 and 8 weeks after enrollment, 32 weeks of gestation, and 6 weeks
      postpartum. SETTING: The setting is in a large, urban, obstetrics clinic.
      PARTICIPANTS: Participants were women who were >= 18 years old, <20 weeks of
      gestation, and consumed alcohol during pregnancy. Of 3438 women screened, 330
      eligible women were assigned to usual care (n = 165) or intervention (n=165). Due
      to missing data, we analyzed 125 in the intervention group and 126 in the usual
      care group. MEASUREMENTS: The measurements were the proportion of women with any
      alcohol use and the number of drinks per day, reported via follow-up telephone
      interviews at 4 and 8 weeks after enrollment, 32 weeks of gestation, and 6 weeks,
      6 months, and 12 months postpartum. FINDINGS: In random effects models adjusted
      for confounders, the intervention group was less likely to use any alcohol (odds
      ratio 0.50; 95% confidence interval [CI], 0.23-1.09; P=0.08) and consumed fewer
      drinks per day (coefficient -0.11; 95% CI -0.23-0.01; P=0.07) than, the usual
      care group in the postpartum period but these differences were non-significant.
      Missing data during the prenatal period prevented us from modeling prenatal
      alcohol use. CONCLUSIONS: Brief motivational enhancement intervention delivered
      in an obstetrical outpatient setting did not conclusively decrease alcohol use
      during the postpartum period.

PMID- 24315220
TI  - [Treatment of superficial bacterial cutaneous infections: a survey among general
      practitioners in France].
AB  - BACKGROUND: Superficial bacterial skin infection and superinfection of skin
      diseases are usually treated by general practitioners using antiseptics or
      antibiotics. However, acquired resistance to biocidal agents, both systemic and
      topical, is growing. OBJECTIVES OF THE STUDY: Our aim was to assess the skill of
      GPs in clinical situations involving common skin infections. MATERIAL AND
      METHODS: On 16 June 2010, we sent a questionnaire to all GPs in a rural region of
      France (the Cher department) together with a stamped addressed envelope for the
      reply. The questionnaire contained seven pages of multiple-choice questions and
      five clinical cases, each one illustrated with a photograph (sty, furuncle,
      whitlow, colonized chronic wounds and impetigo). Anonymity of responses was
      guaranteed. Data was analysed using the Clinsight((r)) software package. RESULTS:
      The response rate was 51% (102 responses). GPs reported little difficulty in
      treating these patients (median 3, range 1 to 8 on a scale of increasing
      difficulty from 0 to 10). The main results of the study are firstly the frequency
      of combination of at least one antiseptic with one antibiotic (46%); secondly,
      the frequency of combination of two antibiotics (20% of cases); thirdly, the
      frequent prescription of systemic antibiotics for chronic wounds colonized by
      Pseudomonas aeruginosa (61%). DISCUSSION: Our study shows the high frequency of
      prescriptions for combined therapy to treat superficial skin infections despite
      the fact that monotherapy with either an antiseptic or an antibiotic would
      probably suffice. It also shows the unnecessary prescription of antibiotics for
      colonization of a chronic wound. The study was limited in terms of size and
      design: it was a questionnaire rather than an analysis of prescriptions actually
      made in "real life", and the response rate was 51%. In addition, aside from
      impetigo, for which randomised studies and recommendations were given, the other
      surface infections (sty, folliculitis, whitlow) tend to be treated more
      empirically. CONCLUSION: Dissemination of recommendations regarding the
      respective role of antiseptics and antibiotics (and their route of
      administration, topical or systemic) in superficial skin infections would
      doubtless be useful for prescribers, and more rational use of these agents would
      help limit bacterial resistance.

PMID- 24315221
TI  - [Fibrous papules of the face: a retrospective anatomoclinical study of 283
      cases].
AB  - BACKGROUND: Fibrous papules of the face are frequent benign lesions seen in the
      nasal and perinasal region. Their clinical aspect is indistinct and the
      histological signs are sometimes mild or possibly misleading in the case of
      atypical forms. We carried out a retrospective study of 283 fibrous papules
      diagnosed at our histology laboratory. The goal of this study was to characterize
      this type of frequent but occasionally unrecognized lesion. PATIENTS AND METHODS:
      We performed a retrospective study of fibrous papules of the face diagnosed in
      the dermatopathology laboratory of our dermatology centre between January 2002
      and December 2011. The study concerned the clinical information noted in the
      examination request and the morphological abnormalities seen at optical
      microscopy. An immunohistological study of factor XIIIa was performed in selected
      cases. RESULTS: The fibrous papules of the face came from 129 men and 154 women
      aged between 18 and 90 years (mean: 46 years). Two hundred and thirty-seven
      (83.7%) lesions were taken from the nasal region and none were taken from
      anywhere other than the face. The clinically mentioned diagnoses varied. A
      diagnosis of fibrous papule of the face was stated in 42% of cases, and the main
      differential diagnoses were nevus (stated in 34% of cases) and basal cell
      carcinoma (stated in 14% of cases). The fibrous papules were classic in 85.5% of
      cases. We observed 6 variants of fibrous papule: hypercellular, inflammatory,
      pleomorphic, pigmented, clear-cell and granular-cell types. Immunohistochemistry
      of factor XIIIa was positive in all cases except clear-cell fibrous papules.
      DISCUSSION: This study shows that despite their frequency, these lesions often go
      unrecognized, since the hypothesis of a fibrous papule of the face was mentioned
      in fewer than 50% of cases at the time of biopsy. Diagnosis is often made by the
      histopathologist, who may be misled by some rare types. The principal
      differential diagnoses are nevus and basal cell carcinoma, thus warranting
      methodical histological analysis of all pieces.

PMID- 24315222
TI  - [Stigmata: From Saint-Francis of Assisi to idiopathic haematidrosis].
AB  - "Religious" stigmata describe body marks and sores that reflect the crucifixion
      wounds of Christ (hands and wrists, feet, flank, back, shoulders, forehead) and
      which are transferred to an individual through fervent prayer. "Non-religious"
      stigmata usually describe spontaneous episodes of bleeding with no identifiable
      cause outside any religious context. Irrespective of the setting in which they
      occur, such lesions are extremely striking. This review intends to summarize what
      is currently known about stigmata in the light of current medical knowledge,
      while stressing that the "spontaneous" nature of these lesions does not rule out
      a genuine medical cause.

PMID- 24315223
TI  - [Three cases of bullous lupus erythematosus].
AB  - BACKGROUND: Bullous lupus is a subepidermal autoimmune bullous dermatosis, a rare
      entity that forms one of the cutaneous signs of systemic lupus erythematosus. We
      report on the clinical, immunopathological and progressive features of bullous
      lupus in three patients. PATIENTS AND METHODS: Our patients consisted of two
      women and one man aged 34, 22 and 30 years respectively. A diagnosis of bullous
      lupus erythematosus was evoked by blisters or vesicular blisters and confirmed,
      in addition to criteria for the diagnosis of systemic lupus erythematosus, by the
      presence of subepidermal blistering with infiltrate containing neutrophils and
      eosinophils as revealed by histological analysis, and of deposits of IgG and IgM
      (two cases) or of IgA (one case) at the dermo-epidermal junction observed under
      direct immunofluorescence. Indirect immunofluorescence showed anti-collagen VII
      antibodies. Lupus nephritis was present in two cases. Our patients were treated
      with corticosteroids and immunosuppressants. CONCLUSION: Bullous lupus
      erythematosus may be the first sign of systemic lupus erythematosus with severe
      visceral involvement, especially renal involvement, suggesting that it may be a
      marker of activity and prognosis.

PMID- 24315224
TI  - [Anti-p200 pemphigoid: Remission under mycophenolate mofetil (Cellcept(r))].
AB  - BACKGROUND: Anti-p200 pemphigoid is a recently described autoimmune subepidermal
      bullous dermatosis characterized by its target antigen and the associated
      anatomoclinical picture. The treatment is not as yet well defined. PATIENT AND
      METHODS: A 73-year-old man consulted for a pruritic bullous eruption with buccal
      involvement. Direct immunofluorescence revealed linear deposits of IgG and C3 at
      the dermal-epidermal junction. Elisa screening for circulating anti-BP180 and
      anti-BP230 antibodies was negative. A diagnosis of bullous pemphigoid was
      suspected. After an unfavourable clinical outcome under clobetasol and then
      prednisolone and methotrexate, other immunological tests were performed. Indirect
      immunofluorescence on NaCl-cleaved skin revealed a deposit of IgG4 antibodies on
      the dermal side. Immunoblotting showed antibodies directed against a 200-kDa
      antigen on a dermal extract. A diagnosis of anti-p200 pemphigoid was made. The
      patient was treated with dapsone combined with prednisolone. Seventy-two hours
      later, treatment was stopped due to hepatic cytolysis related to immunoallergic
      hepatitis. Treatment with mycophenolate mofetil was then initiated and resulted
      in complete remission, which persisted at seven months. DISCUSSION: The diagnosis
      of anti-p200 pemphigoid was made on the basis of a set of clinical and
      immunological factors. Anti-p200 pemphigoid differs from standard bullous
      pemphigoid in terms of more frequent cephalic, acral and mucous membrane
      involvement, as well as a greater degree of miliary scarring. There was no
      eosinophilia. Elisa screening for anti-BP180 and anti-BP230 antibodies was
      negative. Immunoblotting showed antibodies directed against a 200kDa protein on
      dermal extract. The treatment is not well defined, even if dapsone appears to be
      the most effective therapy. To our knowledge, our patient is the first to be
      successfully treated with mycophenolate mofetil. CONCLUSION: Treatment of anti
      p200 pemphigoid is difficult. In our case, treatment by mycophenolate mofetil was
      effective and could offer an alternative to dapsone.

PMID- 24315225
TI  - [Transition from pemphigus vulgaris to pemphigus foliaceus: a case report].
AB  - BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are the two main
      subtypes of auto-immune pemphigus, each having different clinical, histological
      and immunopathological features. We report the case of a patient initially with
      typical PV who relapsed within 2years, presenting clinically, histologically and
      immunologically typical PF. PATIENTS AND METHODS: A 47-year old man presented in
      March 2008 with clinically, histologically and serologically typical PV and
      treated with systemic corticosteroids alone (prednisone: 1mg/kg per day) then
      combined with a cycle of rituximab, which resulted in complete remission. After
      discontinuation of therapy (duration: 26months), he relapsed 6 months later with
      PF presenting clinical, histological and serological characteristics typical of
      this condition. DISCUSSION: This is a rare case of complete transition from PV to
      PF in clinical, histological and serological terms, and the first case occurring
      after initial treatment with rituximab.

PMID- 24315226
TI  - [Efficacy of acitretin in IgA pemphigus].
AB  - BACKGROUND: IgA pemphigus is a particular entity among autoimmune blistering
      intraepidermal diseases. IgA pemphigus is subdivided into two types:
      intraepidermal neutrophilic IgA dermatosis and subcorneal pustular dermatosis.
      PATIENTS AND METHODS: We report the case of an 82-year-old woman with
      intraepidermal neutrophilic IgA pemphigus associated with IgA gammopathy. The
      histopathological findings were unusual, with numerous large subcorneal pustules,
      a few pustules in the stratum spinosum, and basal IgA deposition. A favourable
      outcome was achieved with acitretin. DISCUSSION: This observation is significant
      in that it highlights the difficulty of classification of IgA pemphigus, which is
      currently based on clinical and histopathological findings. There is currently no
      therapeutic consensus attitude but simply a set of empirical data.

PMID- 24315227
TI  - [Sneddon-Wilkinson disease: efficacy of intermittent adalimumab therapy after
      lost response to infliximab and etanercept].
AB  - BACKGROUND: Sneddon-Wilkinson disease (SWD) is a rare chronic neutrophilic
      dermatosis. The first-line treatment is dapsone but resistance to treatment may
      sometimes pose a challenge. CASE REPORT: We report a multidrug-resistant patient
      who responded dramatically before gradually losing response to infliximab and
      then etanercept. Complete remission was again obtained with adalimumab.
      DISCUSSION: Our case confirms the previously reported dramatic efficacy of anti
      TNF biological agents in recalcitrant SWD but highlights the possibility of
      subsequent loss of response. Furthermore, it illustrates the efficacy of
      adalimumab in this indication.

PMID- 24315228
TI  - [Occurrence of vitiligo in a patient with ankylosing spondylitis receiving
      adalimumab].

PMID- 24315229
TI  - [A "tattooed" lymph node mimicking metastatic melanoma].

PMID- 24315230
TI  - [The metamorphosis of plica].

PMID- 24315231
TI  - [Circumcision and dermatology].

PMID- 24315232
TI  - [Antinuclear antibodies: what dermatologists need to know].

PMID- 24315233
TI  - [Pigmented nodular melanoma].

PMID- 24315234
TI  - [The contribution of reflectance confocal microscopy in the diagnosis of Paget's
      disease of the breast].

PMID- 24315235
TI  - [Autosomal dominant (familial) infantile myofibromatosis: The causative role of
      mutations in PDGFRB and NOTCH3].

PMID- 24315236
TI  - [Adult xanthogranuloma at the base of the nose].

PMID- 24315237
TI  - [Dowling-Degos disease and chronic hidradenitis suppurativa].

PMID- 24315238
TI  - [Sunitinib-induced pyoderma gangrenosum].

PMID- 24315239
TI  - Bipedal and quadrupedal locomotion in chimpanzees.
AB  - Chimpanzees (Pan troglodytes) habitually walk both bipedally and quadrupedally,
      and have been a common point of reference for understanding the evolution of
      bipedal locomotion in early ape-like hominins. Here we compare the kinematics,
      kinetics, and energetics of bipedal and quadrupedal walking and running in a
      sample of five captive chimpanzees. Kinematics were recorded using sagittal-plane
      digital high-speed video of treadmill trials. Kinetics were recorded via a
      forceplate. Metabolic energy cost was measured via steady-state oxygen
      consumption during treadmill trials. Consistent with previous work on chimpanzees
      and other hominoids, we found that the spatiotemporal characteristics, joint
      angles, ground reaction forces, and metabolic cost of bipedal and quadrupedal
      locomotion are similar in chimpanzees. Notable differences include hip and trunk
      angles, which reflected a more orthograde trunk posture during bipedalism, and
      mediolateral ground reaction forces, which were larger during bipedal walking.
      Stride frequencies were also higher (and step lengths shorter) during bipedal
      trials. Bipedal and quadrupedal walking among chimpanzees was similar to that
      reported for bonobos, gibbons, and other primates. The similarity in cost between
      bipedal and quadrupedal trials suggests that the adoption of bipedal walking
      would have had no effect on walking costs for early ape-like hominins. However,
      habitual bipedalism may have favored modifications of the hip to allow a more
      orthograde posture, and of the hind limb abductor mechanisms to efficiently exert
      mediolateral ground forces. 

PMID- 24315240
TI  - Animal-assisted therapies are becoming more common.

PMID- 24315241
TI  - Colorectal surgery patients' pain status, activities, satisfaction, and beliefs
      about pain and pain management.
AB  - This study describes surgical colorectal cancer patients' pain levels, recovery
      activities, beliefs and expectations about pain, and satisfaction with pain
      management. A convenience sample of 50 adult inpatients who underwent colorectal
      surgery for cancer participated. Patients were administered the modified American
      Pain Society Patient Outcome Questionnaire on postoperative day 2 and asked to
      report on their status in the preceding 24 hours. Patients reported low current
      (mean 1.70) and average (mean 2.96) pain scores but had higher scores and greater
      variation for worst pain (mean 5.48). Worst pain occurred mainly while turning in
      bed or mobilizing, and 25% of patients experienced their worst pain at rest.
      Overall, patients expected to have pain after surgery and were very satisfied
      with pain management. Patients with worst pain scores >7 reported interference
      with recovery activities, mainly general activity (mean 5.67) and walking ability
      (mean 5.15). These patients were likely to believe that "people can get addicted
      to pain medication easily" (mean 3.39 out of 5) and that "pain medication should
      be saved for cases where pain gets worse" (mean 3.20 out of 5). These beliefs
      could deter patients from seeking pain relief and may need to be identified and
      addressed along with expectations about pain in the preoperative nursing
      assessment. 

PMID- 24315242
TI  - The 6-minute walk test in female fibromyalgia patients: relationship with
      tenderness, symptomatology, quality of life, and coping strategies.
AB  - The purpose of this study was to examine the relationship between the 6-minute
      walk test (6-MWT) and tenderness, symptomatology, quality of life, and coping
      strategies in women with fibromyalgia. One hundred eighteen women with
      fibromyalgia aged 51.9 +/- 7.3 years participated in the study. The examination
      included the 6-MWT, tender points, and the following questionnaires: Fibromyalgia
      Impact Questionnaire (FIQ), Short-Form Health Survey 36 (SF-36), and Vanderbilt
      Pain Management Inventory. Fair correlations between the 6-MWT and the subscales
      of physical impairment (FIQ) and physical function (SF-36) were observed (rho 
      0.365 and 0.347, respectively, both p < .001). The 6-MWT showed a weak
      relationship with tenderness (rho 0.201 and -0.191 for algometer score and tender
      points count, respectively, both p < .05). The relationship between the 6-MWT and
      global score of FIQ, and FIQ subscales of pain and fatigue were weak (rho -0.201,
      -0.211, and -0.226, respectively, all p < .05). The 6-MWT showed a weak
      relationship with bodily pain and vitality scales of SF-36 (rho 0.256 and 0.258,
      respectively, both p = .005) and with passive and active coping strategies (rho 
      0.255 and 0.223, both p < .05). This study in women with fibromyalgia shows
      significant relationships, ranging from weak to fair, between the 6-MWT and
      tenderness, symptomatology, quality of life, and coping strategies. These
      findings indicate that functional capacity, as assessed by the distance walked in
      6 minutes, might be important when planning the assessment, treatment, and
      monitoring of patients with fibromyalgia. 

PMID- 24315243
TI  - Effect of a virtual pain coach on pain management discussions: a pilot study.
AB  - There is a need to enhance patient and practitioner pain communications. A pain
      communication plus virtual pain coach intervention was tested in the primary care
      setting for the effect on communication of osteoarthritis pain information by
      older adults aged >=60 years, on practitioners' pain management changes, and on
      older adults' reduced pain and depressive symptoms 1 month later. A randomized
      controlled pilot study design was used. Twenty-three older adults with
      osteoarthritis pain were randomly assigned to the pain communication plus virtual
      pain coach group or the pain communication-only group. Pain communication
      consisted of a video of important osteoarthritis pain information. The coach
      consisted of practicing out loud with a virtual pain coach via laptop computer.
      Pain and depressive symptoms were measured with, respectively, the Brief Pain
      Inventory Short Form and the Beck Depression Inventory II before intervention and
      1 month later. Immediately after the intervention, older adults had their primary
      care visits, which were audiotaped, transcribed, and content analyzed for older
      adults' communicated pain information and practitioners' pain management changes.
      Older adults in the pain communication plus virtual pain coach group described
      significantly more pain source information and were prescribed significantly more
      osteoarthritis pain treatments than older adults in the pain communication-only
      group. A nonsignificant trend in pain intensity and depressive symptoms reduction
      resulted for older adults in the pain communication plus virtual pain coach group
      1 month later. The virtual pain coach presents a possible strategy for increasing
      pain management discussions between practitioners and older adults with
      persistent pain. 

PMID- 24315244
TI  - Development and validation of a Brazilian version of the short-form McGill pain
      questionnaire (SF-MPQ).
AB  - The aim of this study was to develop and validate a short form of the Brazilian
      version of McGill Pain Questionnaire (SF-MPQ). Three hundred two patients with
      chronic pain filled out the validated Brazilian long form of the McGill Pain
      Questionnaire (LF-MPQ). Words chosen by >=25% of the patients were selected to
      comprise the SF-MPQ. The Brazilian SF-MPQ consisted of 15 descriptors (8 sensory,
      5 affective, and 2 evaluative) rated on a binary mode (present or absent). Four
      pain scores were derived by counting the words chosen by the patients for
      sensory, affective, evaluative, and total descriptors. The SF-MPQ showed poor
      internal consistency (KR-20 = 0.52) but possibly acceptable because it showed
      discriminant validity to discriminate patients presenting different levels and
      mechanisms of pain, and it was strongly correlated with the LF-MPQ. The low KR-20
      coefficient could result from the small number of items. The Brazilian version of
      the SF-MPQ proved to be a useful instrument to evaluate the different qualities
      of pain. It is a reliable option to the long-form MPQ. 

PMID- 24315245
TI  - Pain management education in long-term care: it can make a difference.
AB  - Acute and chronic pain management for persons residing in long-term care settings
      is a serious problem. In an effort to change practice in pain management and
      improve resident outcomes, the Campaign Against Pain education program was
      instituted at Beatitudes Health Care Center in Phoenix, Arizona. In this pilot
      study, professional and certified nursing assistant (CNA) staff were surveyed
      before and after the training program to ascertain change in knowledge,
      attitudes, and barriers about pain. After the intensive training program and
      onsite consultation with the concomitant changes in policies, procedures, and
      documentation, professional and CNA staff knowledge improved after 6 months (F =
      6.273; p = .02), attitudes changed (F = 12.26; p = .002), and barriers were
      mitigated. With a comprehensive quality improvement pain plan in place, the
      findings suggest that education in pain management in long-term care and program
      changes that adopt best practices in pain can make a difference. 

PMID- 24315246
TI  - Early experience with a brief, multimodal, multidisciplinary treatment program
      for fibromyalgia.
AB  - Fibromyalgia is a complex heterogeneous disorder for which a multidisciplinary
      individualized approach is currently advocated. We executed a 1-week
      multidisciplinary fibromyalgia clinical program with seven patients, based on our
      experience with our existing 1.5-day multidisciplinary fibromyalgia program that
      has demonstrated both short- and long-term benefits. The current expanded program
      was not designed as a clinical study, but rather as a clinical feasibility
      assessment, and it was multidisciplinary in nature, with cognitive behavioral
      therapy, activity pacing, and graded exercise therapy as major components. We
      assessed changes in individual patients at 1 week and 3 months after the program
      with the use of validated self-report measures of pain, fatigue, and self
      efficacy. All patients indicated at least small improvements in pain and physical
      symptoms at both 1 week and 3 months, and all but one patient showed improvement
      in self-efficacy at 1 week and 3 months. Similar trends were observed for
      fatigue. Based on our early clinical experience, we conclude that the 1-week
      multidisciplinary fibromyalgia program is logistically feasible and has potential
      for clinical efficacy. Further research is needed and is planned to test the
      clinical efficacy of this program and compare it with other interventions. 

PMID- 24315247
TI  - Methods used by female nurses and lay women for everyday pain management.
AB  - There are numerous types of pain, with different clinical meanings. Everyday pain
      might be experienced by everyone under different stressors, such as lack of
      sleep, alcohol overuse, stay in a stuffy room, and physical overstressors. It
      also might be related to a job character or attitudes. The aim of the present
      study was to investigate the methods for the management of everyday pain used by
      female nurses and lay women. Headaches and back pain were the most common pains
      reported among the female population included in this study. Analgesic use was
      the most common method for management of everyday pain. Nurses used prescription
      medicine and other methods. Lay women used over-the-counter analgesics more
      often. There is a significant tendency to exceed the maximum analgesic dose when
      treating migraines, total body pain, and toothaches. The majority of all of the
      women included in this study used analgesics according to recommendations. Nurses
      were found to underuse analgesics and lay women to overuse the recommended dose.
      Speed and safety were identified as key factors driving studied respondents'
      decisions when treating pain. 

PMID- 24315248
TI  - Review of pain content in three-year preregistration pediatric nursing courses in
      the United Kingdom.
AB  - The results of several studies suggest that gaps remain in nurses' knowledge
      about pain in children, and particularly regarding pain assessment, analgesic
      drugs, and nondrug methods, suggesting a need to explore the pain content of
      preregistration nursing curricula. Over the past decade, the way nurse education
      is delivered has changed with the advent of the internet and the use of virtual
      learning environments. This study, therefore, explored the depth and breadth of
      pain content in 3-year preregistration pediatric nursing courses across the U.K.
      as well as ascertaining how this content is delivered. The leads for pediatric
      nursing at all 56 U.K. higher education institutions running the 3-year
      preregistration pediatric nursing course were e-mailed a questionnaire.
      Participants were asked to indicate whether topics are covered in the program,
      and if so how it was delivered. Results suggest that preregistration pediatric
      nursing courses in the U.K. do not always equip students to manage pain
      effectively in clinical practice. There appears to be limited content on pain in
      nursing curricula, with several institutions not covering key topics. Most
      teaching is delivered face to face with limited workbooks and virtual learning
      activities. Further research is needed in this area to ascertain the impact of
      this on the quality of care provided. 

PMID- 24315249
TI  - Patterns and clinical correlates of pain among brain injury patients in critical
      care assessed with the critical care pain observation tool.
AB  - This study was conducted to assess the patterns and clinical correlates of acute
      pain in brain injury patients during the critical care period using the Critical
      Care Pain Observation Tool (CPOT). Data were collected from 31 brain-injury
      patients admitted to an intensive care unit (ICU) at a university hospital
      located in Incheon, Republic of Korea. Glasgow Coma Scale and CPOT scores were
      assessed on days 1, 3, 6, 9, and 14 after ICU admission. Results showed that
      temporal changes in pain intensity displayed a consistent pattern in critical
      care patients with a brain injury during the first 14 days of ICU admission. Mean
      pain score was highest on day 1, decreased rapidly to reach a minimum on day 3 or
      6, and then increased on day 9. In most patients, pain reduced slightly on day
      14. Mean CPOT scores were significantly higher in the nonsurgery group than in
      the surgery group. There was also a nonsignificant trend of higher pain intensity
      scores among patients with moderate brain injury compared with those with severe
      injury. CPOT scores immediately after endotracheal suctioning were significantly
      higher than before endotracheal suctioning, but CPOT scores 20 minutes after
      suctioning were similar to those before suctioning. The present study may be
      meaningful in terms of presenting valid clinical information regarding the
      patterns and characteristics of acute pain in brain injury patients who are often
      unable to self-report on the presence and intensity of pain. 

PMID- 24315250
TI  - Fibromyalgia's key symptoms in normal-weight, overweight, and obese female
      patients.
AB  - Factors affecting the symptomatology of fibromyalgia (FM) are not fully
      understood. The aim of the present study was to analyze the relationship of
      weight status with pain, fatigue, and stiffness in Spanish female FM patients,
      with special focus on the differences between overweight and obese patients. The
      sample comprised 177 Spanish women with FM (51.3 +/- 7.3 years old). We assessed
      tenderness (using pressure algometry), pain and vitality using the General Health
      Short-Form Survey (SF36), and pain, fatigue, morning tiredness, and stiffness
      using the Fibromyalgia Impact Questionnaire (FIQ). The international criteria for
      body mass index was used to classify the patients as normal weight, overweight,
      or obese. Thirty-two percent were normal-weight, 35% overweight, and 32% obese.
      Both overweight and obese patients had higher levels of pain than normal-weight
      patients, as assessed by FIQ and SF36 questionnaires and tender point count (p <
      .01). The same pattern was observed for algometer score, yet the differences were
      not significant. Both overweight and obese patients had higher levels of fatigue,
      and morning tiredness, and stiffness (p < .05) and less vitality than normal
      weight patients. No significant differences were observed in any of the variables
      studied between overweight and obese patients. In conclusion, FM symptomatology
      in obese patients did not differ from overweight patients, whereas normal-weight
      patients significantly differed from overweight and obese patients in the studied
      symptoms. These findings suggest that keeping a healthy (normal) weight is not
      only associated with decreased risk for developing FM but might also be a
      relevant and useful way of improving FM symptomatology in women. 

PMID- 24315251
TI  - Complementary and alternative medicine: nurses' attitudes and knowledge.
AB  - Despite significant evidence for the integration of complementary and alternative
      medicine (CAM) into professional nursing practice, gaps exist regarding nurses'
      baseline knowledge, beliefs of efficacy, and learning needs for further education
      to facilitate the integration of CAM into nursing practice. The top three
      conditions which adults identified for using CAM were back pain, neck pain, and
      joint pain. CAM can offer nurses additional treatment options for managing their
      patients' pain and discomfort. The California Board of Registered Nursing (BRN)
      identifies that nurses can help provide the missing link between conventional
      Western medicine and CAM therapies. Nurses cannot successfully advocate for CAM
      therapies, nor understand their patients' prior use of such treatments, unless
      they themselves are familiar with both the risks and the benefits of these
      practices. It is necessary to first establish nurses' baseline knowledge and
      beliefs related to CAM so that adequate educational programs can be initiated to
      help mitigate the barriers to incorporating CAM into the acute care setting. This
      descriptive study explores registered nurses' attitudes and knowledge related to
      CAM by using the Nurse Complementary and Alternative Medicine Nursing Knowledge
      and Attitudes Survey developed by Rojas-Cooley and Grant. Nurses in this study
      demonstrated limited self-reported knowledge of basic CAM terminology and CAM
      practices. 

PMID- 24315253
TI  - Pain and anxiety during bone marrow biopsy.
AB  - A bone marrow biopsy is considered to be painful, often causing anxiety. We
      observed large differences between patients and wondered which factors cause pain
      and anxiety. In a prospective study, 202 patients were analyzed. Experienced
      hematologists and fellows in training (17% of biopsies) performed bone marrow
      aspirates and biopsies from the posterior iliac crest. Demographics, disease
      category, performance score, source of information, number of previous biopsies,
      experience of the hematologist, and length and quality of the biopsy were
      recorded. Pain and anxiety were measured using a visual analog scale and verbal
      rating score. Data were subjected to univariate and multivariate regression. The
      median pain score was 1.9 (range 0-10); 21% did not experience any pain. Anxiety
      scored 1.8 (range 0-10), and correlated positively with pain (p = .000). By
      univariate analysis, young age, poor performance, the physician as source of
      information, and prolonged procedures were associated with more pain. In
      multivariate analysis, anxiety, information from the physician, and a prolonged
      procedure persisted. Length or artifacts of the core biopsy did not correlate
      with pain. In conclusion, bone marrow biopsies performed in an optimal setting by
      experienced hematologists cause only mild pain, with, however, some patients
      experienced serious problems. To reduce pain, not only careful local anesthesia,
      but also the addition of systemic analgesics and especially anxiety reduction
      seems to be useful. 

PMID- 24315254
TI  - Nursing knowledge and beliefs regarding patient-controlled oral analgesia (PCOA).
AB  - Patient-controlled oral analgesia (PCOA) allows patients to self-administer oral
      opioids for pain management. Advantages of PCOA include improved pain control
      with lower doses of opioids, decreased length of stay, increased patient
      satisfaction, and better functional outcomes than conventional nurse-administered
      oral analgesia. Sucessful PCOA programs are well described in the literature.
      However, nurses have concerns about allowing patients to self-administer opioids.
      The purpose of this study was to identify nurses' knowledge and beliefs regarding
      PCOA. Nurses who work at the Holland Orthopaedic and Arthritic Centre were asked
      to complete a survey exploring their beliefs regarding PCOA. The nurses were
      asked to complete the same survey twice: before an education program in February
      2010, and 3 months after implementation of PCOA in June 2010. In February 2010,
      74 nurses and in June 2010, 32 nurses participated in the survey. Some nurses
      (18%) had previous experience with PCOA. At both the pre-education and the
      postimplementation times, nurses thought that the PCOA program reduced wait times
      for analgesics and improved patient satisfaction with pain management. Before
      program implementation, negative beliefs included that patients on the PCOA
      program would lose their analgesics, would give their analgesics to visitors or
      other patients, and were at risk for having their analgesics stolen and that the
      nurse was liable if the patient's analgesics were lost or stolen. After program
      implementation, no nurse believed that patients would lose their analgesics or
      give their analgesics to visitors or other patients or that they were liable for
      lost or stolen analgesics. However, nurses continued to think that patients were
      at risk for having their analgesics stolen. We found that nurses were concerned
      that analgesics could be lost, misused, or stolen and that they would be liable
      for lost analgesics. These findings were consistent with literature discussing
      patients' outcomes regarding PCOA. However, after education and experience these
      concerns decreased or resolved. It is important to address these concerns before
      PCOA program implementation. 

PMID- 24315252
TI  - A biopsychosocial-spiritual model of chronic pain in adults with sickle cell
      disease.
AB  - Chronic pain in adults with sickle cell disease (SCD) is a complex
      multidimensional experience that includes biologic, psychologic, sociologic, and
      spiritual factors. To date, three models of pain associated with SCD (i.e.,
      biomedical model, biopsychosocial model for SCD pain, and Health Beliefs Model)
      have been published. The biopsychosocial multidimensional approach to chronic
      pain developed by Turk and Gatchel is a widely used model of chronic pain.
      However, this model has not been applied to chronic pain associated with SCD. In
      addition, a spiritual/religious dimension is not included in this model. Because
      spirituality/religion is central to persons affected by SCD, that dimension needs
      to be added to any model of chronic pain in adults with SCD. In fact, data from
      one study suggest that spirituality/religiosity is associated with decreased pain
      intensity in adults with chronic pain from SCD. A biopsychosocial-spiritual model
      is proposed for adults with chronic pain from SCD, because it embraces the whole
      person. This model includes the biologic, psychologic, sociologic, and spiritual
      factors relevant to adults with SCD based on past and current research. The
      purpose of this paper is to describe an adaptation of Turk and Gatchel's model of
      chronic pain for adults with SCD and to summarize research findings that support
      each component of the revised model (i.e., biologic, psychologic, sociologic,
      spiritual). The paper concludes with a discussion of implications for the use of
      this model in research. 

PMID- 24315255
TI  - Cranial electrical stimulation improves symptoms and functional status in
      individuals with fibromyalgia.
AB  - To investigate the effects of microcurrent cranial electrical stimulation (CES)
      therapy on reducing pain and its associated symptoms in fibromyalgia (FM), we
      conducted a randomized, controlled, three-group (active CES device, sham device,
      and usual care alone [UC]), double-blind study to determine the potential benefit
      of CES therapy for symptom management in FM. Those individuals using the active
      CES device had a greater decrease in average pain (p = .023), fatigue (p = .071),
      and sleep disturbance (p = .001) than individuals using the sham device or those
      receiving usual care alone over time. Additionally, individuals using the active
      CES device had improved functional status versus the sham device and UC groups
      over time (p = .028). 

PMID- 24315256
TI  - Concerns about pain and prescribed opioids in Taiwanese oncology outpatients.
AB  - Pharmacologic agents are considered to be a cornerstone of cancer pain
      management. Patients' concerns about use of analgesics are likely to lead to poor
      pain management. The purpose of this study was to describe participants'
      responses to their beliefs regarding pain and prescribed opioids. Ninety-two
      outpatients age >=18 years who had taken prescribed opioid analgesics for cancer
      related pain in two teaching hospitals in the Taipei area completed the Pain
      Opioid Analgesics Beliefs Scale-Cancer. An important finding of this study is
      that large numbers of patients had misconceptions about using opioids for pain.
      Between 33.7% and 68.5% of the patients in this study held negative beliefs about
      opioids and beliefs about pain. Specifically, 68.5% of the patients agreed that
      "opioid medication is not good for a person's body." Many patients (62%) agreed
      that "the more opioid medicine a patient used, the greater the possibility that
      he/she might rely on the medicine forever," and 61.0% agreed that "if a patient
      starts to use opioid medicine at too early a stage, the medicine will have less
      of an effect later." Two-thirds (66.3%) of the sample agreed that adult patients
      should not use opioid medicine frequently. The findings provide empirical support
      for the need for better programmatic efforts to improve beliefs of pain and
      analgesics in Taiwanese oncology outpatients. 

PMID- 24315257
TI  - Turkish pediatric surgical nurses' knowledge and attitudes regarding pain
      assessment and nonpharmacological and environmental methods in newborns' pain
      relief.
AB  - Effective pain management requires accurate knowledge, attitudes, and assessment
      skills. The purpose of the present study was to describe Turkish pediatric
      surgical nurses' knowledge and use of pain assessment and nonpharmacologic and
      environmental methods in relieving newborn's pain in hospital. The sample
      consisted of 111 pediatric surgical nurses employed in pediatric surgical unit in
      15 university hospitals located in Turkey. A questionnaire was used to measure
      the nurses' knowledge and use of pain assessment, nonpharmacologic, and
      environmental methods. Data were analyzed with the use of descriptive statistics.
      Of the nurses that participated in the study, 83.8% were between the ages of 20
      and 35 years, 54.1% had a bachelor degree, and 75.7% had a nursing experience
      <=10 years. 50.5% stated that physiologic and behavioral indicators used in the
      assessment of pain in infants. The most commonly used nonpharmacologic methods
      were giving nonnutritive sucking, skin-to-skin contact, and holding. The most
      commonly used environmental methods were avoiding talking loudly close to the
      baby, minimal holding, care when opening and closing of the incubator, avoiding
      making noise when using wardrobe, drawers, trash, or nearby devices, such as
      radio and television, avoiding sharp fragrances, such as alcohol, perfume, near
      the baby, and reducing light sources. Although Turkish pediatric surgical nurses
      used some of the nonpharmacological and environmental methods in infant's pain
      relief, there remains a need for more education about pain management and for
      more frequent use of these methods in clinical care. 

PMID- 24315258
TI  - Postoperative pain: nurses' knowledge and patients' experiences.
AB  - The aim of this study was to determine nurses' knowledge and attitudes regarding
      postoperative pain and identify postoperative patients' pain intensity
      experiences. The assessment and management of acute postoperative pain is
      important in the care of postoperative surgical patients. Inadequate relief of
      postoperative pain can contribute to postoperative complications such as
      atelectasis, deep vein thrombosis, and delayed wound healing. A pilot study with
      an exploratory design was conducted at a large teaching hospital in the eastern
      United States. The convenience samples included 31 nurses from the
      gastrointestinal and urologic surgical units and 14 first- and second-day adult
      postoperative open and laparoscopic gastrointestinal and urologic patients who
      received patient-controlled analgesia (PCA). The Knowledge and Attitudes Survey
      Regarding Pain was used to measure nurses' knowledge about pain management. The
      Short-Form McGill Pain Questionnaire (SF-MPQ) was used to measure patients' pain
      intensity. The nurses' mean score on the Knowledge and Attitudes Survey Regarding
      Pain was 69.3%. Patients experienced moderate pain, as indicated by the score on
      the SF-MPQ. There is a need to increase nurses' knowledge of pain management. 

PMID- 24315259
TI  - Decoding the role of epigenetics and genomics in pain management.
AB  - Persistent pain is a costly epidemic, affecting >50 million Americans with
      estimated expenditures of >$200 billion annually for direct care and lost
      productivity. Recent advances in epigenetic/genomic understanding of pain and
      analgesic response may lead to improvements in pain management and help curtail
      costs by providing more precise detection of the pain mechanisms involved and
      thereby more personalized and effective treatments. However, the translation of
      epigenetic and genomic strategies for pain management into clinical practice will
      depend on understanding their potential applications. The purpose of this article
      is to examine current knowledge about epigenetic and genomic mechanisms of
      persistent pain and potential opportunities for improving pain management. The
      initial discussion focuses on present understanding of nociceptive pathways and
      alterations that lead to pathologic pain. The discussion then moves to a review
      of epigenetic mechanisms that have been identified in the transition to and
      maintenance of persistent pain as well as in the individual's response to
      analgesics. Potential applications of epigenetics/genomics to identify people at
      risk and possibly prevent persistent pain and guide diagnosis and the selection
      of therapeutic modalities are presented. 

PMID- 24315260
TI  - Bridging the gap between mind and body: a biobehavioral model of the effects of
      guided imagery on pain, pain disability, and depression.
AB  - Chronic noncancer pain (CNCP) is a common and complex disorder associated with
      declines in physical health and functional status, emotional well-being, and
      quality of life. To best address the complexity of this condition, research and
      clinical practice for CNCP should be guided by a framework incorporating both
      biologic and psychologic factors. This article presents a biobehavioral model of
      chronic pain that hypothesizes mechanisms related to the effectiveness of a
      complementary therapy, guided imagery (GI), for this population. Using the
      research-to-model/theory strategy, we mapped findings from published reports of
      interdisciplinary research into physiologic and psychologic aspects of the nature
      and mechanisms of pain, as well as the use of GI for pain, to build the model of
      GI's effects on pain, pain disability, and depression. In the model, these
      outcomes of GI for persons experiencing CNCP are mediated by psychologic (pain
      self-efficacy and pain beliefs) and physiologic (immune-mediated analgesia and
      sickness response) variables. A biobehavioral approach to nursing phenomena will
      advance understanding of health and health-related issues and has the potential
      to improve outcomes through delineation of mechanisms underlying relationships
      between psychologic and biologic factors. Increased consumer use of complementary
      therapies to treat pain, the current cost-driven health care system, and the
      mandate for evidence-based practice support the need to validate the efficacy of
      such therapies. This empirically derived model provides a framework for practice
      and research for nurses and other health care providers to promote health,
      function, and well-being in persons with CNCP. 

PMID- 24315261
TI  - American Society for Pain Management Nursing (ASPMN) position statement: male
      infant circumcision pain management.
AB  - The ASPMN strongly recommends that infants who are being circumcised must receive
      optimal pain management. ''If a decision for circumcision is made, procedural
      analgesia should be provided'' (AAP, 1999, p. 691). Therefore, it is the position
      of the ASPMN that optimal pain management must be provided throughout the
      circumcision process. Furthermore, parents must be prepared for the procedure and
      educated about infant pain assessment. They must also be informed of
      pharmacologic and integrative pain management therapies that are appropriate
      before, during, and after the procedure.

PMID- 24315262
TI  - A comparison between behavioral and verbal report pain assessment tools for use
      with residents in long term care.
AB  - The purpose of this study was twofold: (1) to evaluate four pain assessment tools
      for use with long-term care (LTC) residents who were both able and not able to
      verbally report their pain; and (2) to assess whether pain behaviors displayed by
      LTC residents vary as a function of ability to self-report pain. We examined the
      differences between these two groups of residents in terms of specific pain
      behaviors assessed through the Pain Assessment Checklist for Seniors with Limited
      Ability to Communicate (PACSLAC) and Pain Assessment in the Communicatively
      Impaired (PACI). We also examined the interrater reliability, and concurrent and
      construct validity of these two behavioral observation tools and the concurrent
      and construct validity of the two verbal report tools. Data were collected from a
      convenience sample of 338 residents from six LTC homes. The interrater
      reliabilities for the two behavioral observation tools were good, and concurrent
      validity was supported for all four pain assessment tools. Pain behaviors, as
      assessed by the PACSLAC and PACI, varied as a function of resident ability to
      verbally report pain. Residents with inability to self-report pain are more
      nonverbally responsive, although certain behaviors (such as guarding and touching
      the affected area) are seen more frequently in those capable of self-report. Our
      data also provide psychometric support for the assessment methods used in this
      study.

PMID- 24315263
TI  - Qualitative evaluation of a pain intensity screen for children with severe
      neurodevelopmental disabilities.
AB  - The population of individuals with severe and profound intellectual disabilities
      (ID) is extremely heterogeneous, and the unique pain-related behaviors of each
      individual might not be satisfactorily captured using a standardized checklist
      such as the Noncommunicating Children's Pain Checklist or the Revised Faces,
      Legs, Arms, Cry, and Consolability tools. There has been increasing appreciation
      of the importance of recognizing the idiosyncratic pain behaviors of these
      individuals. The investigators developed a tool, the Tailored Observational Pain
      Screen (TOPS), to facilitate recognition of pain in the individual who lacks
      verbal communication, based on caregivers' descriptions of the individual's
      unique pain-related behaviors. The aim of this study was to elicit caregivers'
      evaluations of this personalized pain screen, using qualitative analysis of semi
      structured interviews. The participants were the primary caregivers of 13
      children with severe or profound ID and ongoing pain issues who were interviewed
      after they had used the TOPS for 6 weeks. The investigators identified themes
      from the interviews, including: using the TOPS to recognize and evaluate pain;
      using the TOPS to facilitate communication; limitations of the TOPS; and
      recommendations for its improvement. For clinical purposes, the TOPS shows
      promise as a tool for helping caregivers to share with others the ways that pain
      of these children can be detected. 

PMID- 24315264
TI  - Self-efficacy, pain-related fear, and disability in a heterogeneous pain sample.
AB  - The fear avoidance model of chronic pain is well established for specific chronic
      pain groups and of considerable clinical utility, but it suffers from poor
      generalizability. Therefore, in this study we examined the role of self-efficacy
      (SE) in the relationship between pain-related fear (PRF) and three pain-related
      outcomes-pain severity, disability, and depression-in a more heterogeneous
      chronic pain sample. Sixty-eight participants between the ages of 18 and 75 years
      experiencing chronic pain were recruited from the general public. Participants
      completed a questionnaire that measured catastrophizing, SE, fear of movement,
      avoidance behavior, PRF, pain severity, disability, and depression. In support of
      our first hypotheses, higher SE was associated with: (1) less catastrophizing,
      fear of movement, avoidance of pain, and PRF; and (2) less pain severity,
      disability, and depression. And higher catastrophizing, fear of movement,
      avoidance of pain, and PRF were associated with higher pain severity, disability,
      and depression. Although complete mediation was not found, post hoc examination
      of partial correlations revealed that the relationship between PRF and disability
      was partially mediated by SE; however, SE had no mediatory effect on the
      relationship between PRF and either pain severity or depression. Within the
      constraints of a relatively small sample size, we concluded that within a
      heterogeneous pain population, PRF remains the most integral component of the
      fear avoidance model.

PMID- 24315265
TI  - A qualitative analysis of adolescent, caregiver, and clinician perceptions of the
      impact of migraines on adolescents' social functioning.
AB  - Migraines dramatically affect adolescents' quality of life. One area of
      particular importance is the impact of migraines on adolescents' social
      functioning. To understand the impact of migraines on adolescents' social
      functioning from multiple informants, we performed semistructured interviews with
      adolescents who have migraines, their caregivers, and clinicians who treat
      adolescents who have migraines. Three major themes related to social functioning
      were identified from the adolescent interviews: The need to be alone; lack of
      support from siblings; and the feeling of not being understood by others. The
      caregiver interviews yielded three main themes related to family functioning:
      that plans can change quickly; that family life revolves around helping the child
      with the migraine; and parents' feelings of inadequacy in helping their child.
      There were two main themes derived from the clinician interviews related to
      perception of family functioning: the importance of parental involvement; and the
      role of adolescents' school and social lives in migraine prevention. There are a
      number of unmet needs among adolescents with recurrent migraine and their
      families. Interviews with adolescents, caregivers, and clinicians suggest a
      number of areas for intervention. 

PMID- 24315266
TI  - Training the trainer: An educational course for training pain nursing specialists
      supported by the International Association for the Study of Pain (IASP).
AB  - To train pain nursing specialists through a pain education program, 20 nurses
      from six hospitals in Shanghai Province and seven in six provinces of China
      received the training of 2-month pain education and 4-month clinical practice.
      This nonrandomized pilot study examined the results of tests before and after the
      program, case report evaluations, future plan evaluations, clinical practice, and
      satisfaction questionnaire. After the program, the score of the test increased
      significantly compared with that before the program (44.1 +/- 3.19; paired-sample
      t = 10.363; p < .0001). All of the participants thought that the program had
      broadened their vision, 19 (95%) thought that the program had raised the level of
      their theoretical knowledge in pain management, 17 (85%) thought that the program
      had improved their skills in clinical practice, and 15 (75%) thought that the
      program had played a role in enhancing their research abilities. Considering the
      whole program, most students (n = 17; 85%) were quite satisfied, and 3 (15%) were
      simply satisfied. By content analysis of the opening questions, we found that the
      participants had deeper and broader ideas about nurses' role and pain nursing
      specialists' responsibilities in pain management. The program improved nurses'
      attitudes, knowledge, and skills in pain management. The participants recognized
      pain nursing specialists' responsibilities in pain management more clearly. 

PMID- 24315267
TI  - Music provided through a portable media player (iPod) blunts pain during physical
      therapy.
AB  - This research studied, 25 adult patients who underwent physical therapy to assess
      the analgesic effect of distraction with the use of music during physical
      therapy. Patients randomly underwent physical therapy once with music provided by
      an iPod and once without music. In both sessions patients underwent identical
      physical procedures. At end of both sessions patients filled in 5-item
      questionnaire where they scored pain and other parameters, such as stress,
      enjoyment, interaction, and satisfaction, on 10-cm visual analog scale. The mean
      scores (range, 0-10) of the two sessions were statistically compared. Mean pain
      scores were significantly lower (p = .031) during the session in which patients
      received music (4.8 +/- 2.5) than during the session without music (5.8 +/- 2.3).
      The other items of the questionnaire did not disclose any statistically
      significant difference when the sessions with versus without music were compared.
      Enjoyment (8.5 +/- 1.6), interaction (8.3 +/- 1.9), and satisfaction (8.6 +/-
      1.7) scores with music did not significantly differ in the sessions without music
      (8.5 +/- 2.1, 8.5 +/- 1.9, and, 8.5 +/- 1.5, respectively); mean stress score
      was, 3.9 in both sessions. The conclusion of the study is that music provided
      through a portable media player has an analgesic effect. This can be an effective
      analgesic strategy during painful physical therapy. 

PMID- 24315268
TI  - Fibromyalgia syndrome: is it related to vitamin D deficiency in premenopausal
      female patients?
AB  - There are a number of studies that have evaluated the relationship between
      fibromyalgia (FM) and vitamin D deficiency with conflicting results. The aim of
      this study was to assess vitamin D deficiency in patients with FM and to evaluate
      the relationship with the common symptoms of FM and levels of serum vitamin D.
      Forty premenopausal female fibromyalgia patients and 40 age- and sex-matched
      control subjects were included in the study. The demographic characteristics of
      all subjects, including age, sex, and body mass index, were recorded. The number
      of tender points was recorded, and the intensity of the widespread pain of the
      subjects was measured by the visual analog scale. The activities of daily living
      component of the Fibromyalgia Impact Questionnaire (FIQ-ADL), was used to assess
      physical functional capacity. Serum vitamin D was measured in both groups, and
      vitamin D levels <37.5 nmol/L were accepted as vitamin D deficiency. The vitamin
      D levels and clinical and laboratory characteristics of the patient and control
      groups were comparatively analyzed. The relationship between vitamin D levels and
      clinical findings of the FM patients were also determined. The mean age was 41.23
      +/- 4.8 and 39.48 +/- 4.08 years for the patient and control groups,
      respectively. The pain intensity, number of tender points, and FIQ-ADL scores
      were higher in FM patients than in control subjects. The mean levels of vitamin D
      in the patient and control groups were determined to be 31.97 +/- 15.50 and 28.97
      +/- 13.31 nmol/L, respectively (p > .05). The incidence of vitamin D deficiency
      was similar between the patient and control groups (67.5% vs. 70%). Vitamin D
      levels significantly correlated with pain intensity (r = -0.653; p = .001) and
      FIQ-ADL scores in the FM group (r = -0.344; p = .030). In conclusion, the results
      of this study indicate that deficiency of vitamin D is not more common in
      premenopausal female patients with FM than in control subjects without FM.
      However, the association between pain and vitamin D levels in FM patients
      emphasizes that hypovitaminosis of vitamin D in the FM syndrome may have an
      augmenting impact on pain intensity and functional status. Future studies are
      needed to show the effect of vitamin D supplementation in the reduction of pain
      intensity and disability in patients suffering from this chronic condition. 

PMID- 24315269
TI  - Nurses' views about the barriers and facilitators to effective management of
      pediatric pain.
AB  - Children continue to experience moderate to severe pain during hospitalization.
      This paper presents data from two modified focus groups undertaken as part of a
      larger study exploring pediatric pain management practices in one hospital in the
      south of England. Thirty nurses took part in the focus groups and were asked
      questions about their views about the barriers and facilitators to effective pain
      management in the hospital. Participants identified a number of barriers which
      related to the staff, children and parents and the organization. Nurses indicated
      that they and the medical staff lacked knowledge about pain management. They also
      felt that staff shortages and a heavy workload detracted from the quality of the
      care they could provide. Several participants indicated that insufficient
      analgesic drugs were sometimes prescribed. Many of the barriers identified
      related to parents and children. It appears that nurses may not take as active a
      role as they could do in managing pediatric pain rather seeing it as the parents
      and child's responsibility to let them know when they are experiencing pain.
      Nurses also felt that parents exaggerate their child's pain and ask for analgesic
      drugs before their child needs them. There is a need to explore the interactions
      between nurses, children and parents in this context in more detail. 

PMID- 24315270
TI  - Health-related profile and quality of life among nursing home residents: does
      pain matter?
AB  - The purpose of this exploratory cross-sectional study was to explore the health
      related profile and quality of life among older persons living with and without
      pain in nursing homes. Ten nursing homes were approached, and 535 older persons
      were invited to join the study from 2009 to 2011. The nursing home residents'
      demographic information and information regarding their pain situation and the
      use of oral analgesic drug and nondrug therapy among the older residents with
      chronic pain were also collected. Residents' physical health (using the Barthel
      Activities of Daily Living (ADL) and Elderly Mobility Scores); psychologic
      health, including happiness, life satisfaction, depression, and loneliness (using
      the Happiness Scale, the Life Satisfaction Scale, the Geriatric Depression Scale,
      and the UCLA Loneliness Scale); and quality of life were investigated. Among the
      535 nursing home residents, 396 (74%) of them suffered from pain, with mean pain
      scores of 4.09 +/- 2.19, indicating medium pain intensity a remaining 139 (26%)
      reported no pain. The location of pain was mainly in the knees, back and
      shoulders. Our results demonstrated that, with the exception of the no-pain group
      (p < .05), nursing home residents' pain affected both their psychologic health,
      including happiness, life satisfaction, and depression, and their physical
      quality of life. Nevertheless, only one-half of the older persons with pain used
      oral analgesic drug or nondrug therapy to relieve their pain. Pain had a
      significant impact on their mobility and ADL, was positively correlated with
      happiness and life satisfaction, and was negatively correlated with loneliness
      and depression. Pain management is a high priority in elderly care; as such,
      innovative and interdisciplinary strategies are necessary to enhance quality of
      life particularly for older persons living in nursing homes. 

PMID- 24315271
TI  - Managing pain with algorithms: an opportunity for improvement? Or: the
      development and utilization of algorithms to manage acute pain.
AB  - Pain management in a hospital setting remains a challenge today. Many health care
      providers remain anxious and uninformed regarding analgesic titration within a
      hospital setting. Overcoming the potential risks to obtain the benefits of opiate
      titration is a challenge within any health care setting. Virginia Commonwealth
      University, a tertiary medical center which houses schools of medicine, nursing,
      and pharmacy, evaluated the use of algorithms for managing acute pain. This
      article describes the Pain Committee's efforts and offers one potential
      intervention for safe analgesic opioid titration, an algorithm for acute pain
      management. 

PMID- 24315272
TI  - An ethnography of chronic pain in veteran enlisted women.
AB  - Enlisted women are an essential subpopulation within the United States (U.S.)
      Armed Services, yet little is known about their chronic pain experiences. The
      purpose of this study was to describe veteran enlisted women's chronic pain
      experiences, both while on active duty and since active duty ended. A total of 15
      enlisted women were interviewed. This ethnographic approach produced stories of
      their beliefs, attitudes, and behaviors regarding their chronic pain and the care
      they have received both while serving and after discharge or retirement. The
      findings show that U.S. military culture and training have a major impact on
      enlisted women's chronic pain experiences. Enlisted women learn to ignore or deny
      acute pain because it would hamper their ability to complete their military
      mission. Even when they admit to themselves that they are in pain, they may mask
      the pain from others for fear of being called weak or fear of discrimination and
      ostracism. When the pain can no longer be ignored and they seek health care, they
      are frustrated when their pain reports are not believed by supervisors and health
      care providers. Chronic pain eventually leads to discharge or retirement when
      they can no longer do their job. Health care providers must understand both U.S.
      military culture and enlisted women's strategies concerning pain if they are to
      accurately diagnose and sufficiently treat enlisted women in pain. 

PMID- 24315273
TI  - The effect of a familiar scent on the behavioral and physiological pain responses
      in neonates.
AB  - There are adverse physiologic effects of pain in neonates, and effective pain
      management must be an essential aspect of neonatal care. In this study we
      assessed the effect of a nonmaternal familiar scent on the neonatal pain
      responses. This study included 135 neonates randomly assigned to one of three
      groups. During arterial puncture, one group was exposed to a vanillin scent on a
      gauze pad held next to their nose. They were familiarized with it the night
      before blood sampling by a scented gauze pad placed in the incubator next to
      their head for an average duration of 8.65 hours. The second group was not
      familiarized with the scent but was exposed to it during the procedure. The third
      group was neither familiarized nor exposed to the scent. The duration of crying
      in the familiar scent group was significantly lower than in the two other groups.
      Comparison of the physiologic parameters showed less variation in oxygen
      saturation level during arterial puncture in the familiar scent group. In this
      study, a familiar scent could reduce crying and oxygen consumption during
      arterial puncture. 

PMID- 24315274
TI  - How well is acute pain in children managed? A snapshot in one English hospital.
AB  - This study set out to obtain a picture of pediatric pain management practices in
      one English hospital. Data were collected on two wards. Nonparticipant
      observation combined with a chart audit was used to collect data about actual
      practices. Questionnaires were used to collect information from parents and young
      people. Observational data showed that practices conformed to current guidelines
      in some but not all areas. When prescribed, the dosage of analgesic drugs
      complied with the hospital's guidelines, and drugs were usually administered as
      prescribed. There was some involvement of parents in decision making but this was
      usually initiated by them rather than the nurses. Pain assessment tools were not
      always used nor was a pain history routinely taken. Documentation about pain
      management was limited and there was little evidence of nonpharmacologic methods
      of pain relief being used. Parents and young people felt that their pain
      management was of an acceptable level or very good. This was despite the fact
      that 58% of children experienced severe pain and 24% moderate pain. The results
      provide a snapshot of pain management in one English hospital. As in other
      studies, pain management practices do not adhere to current guidelines in all
      areas, and children appear to be experiencing moderate to severe pain. Despite
      this, parents and children indicated that they were happy with the quality of
      pain management. There is a need to explore this further and to identify
      strategies that support the implementation of guidelines in practice. 

PMID- 24315275
TI  - Validity and reliability of the critical care pain observation tool: a
      replication study.
AB  - Critically ill patients are often not able to self-report the presence of pain.
      Currently there is no generally accepted assessment tool for this population. The
      Critical-Care Pain Observation Tool (CPOT) was developed for pain assessment of
      critically ill patients. The purpose of this study was to replicate the findings
      of the Gelinas et al. (2006) CPOT reference study and examine the interrater
      reliability (IRR), discriminant validity (DV), and criterion validity (CV) of the
      CPOT. This quantitative study used a repeated measures design with a convenience
      sample of 21 postoperative open heart surgery patients cared for in a tertiary
      care teaching hospital. Testing for IRR in this sample showed a range of results
      resulting in fair to almost perfect IRR; the findings of this study suggest that
      the instrument's IRR is acceptable but variable. Testing for DV demonstrated a
      significant difference in mean scores between noxious (painful) and nonnoxious
      (nonpainful) procedures. Testing for CV showed a weak nonsignificant Spearman
      correlation of 0.26 (P < .312) between CPOT scores and patient self-report during
      repositioning after extubation. This replication study adds to four studies that
      have examined psychometric attributes of the instrument and contributes to the
      process of translating the use of this instrument to the clinical setting. 

PMID- 24315276
TI  - Knowledge and attitudes of pain management among nursing faculty.
AB  - A descriptive correlational design was used in this study to examine nursing
      faculty knowledge and attitudes in pain management. Relationships between age,
      education level, pain management preparation, length of time practicing as a
      nurse, length of time teaching nursing, time teaching pain management in the
      classroom, taught pain guidelines in the classroom, and additional continuing
      education about pain management were explored. Ninety-six nursing faculty
      participated from 16 schools of nursing in one Midwestern U.S. region. Findings
      identified that most of the nursing faculty recalled being taught about pain
      management in their basic education, but less than one-half felt adequately
      prepared. Most respondents said that they taught pain management, yet fewer than
      one-half identified that they used specific pain management guidelines. Faculty
      demonstrated adequate knowledge of pain assessment, spiritual/cultural issues,
      and pathophysiology. Areas of weakness were found in medications, interventions,
      and addiction. Faculty that reported teaching pain management in the classroom
      and reported more continuing education missed fewer items. Older nursing faculty
      reported more years of practice, more years of teaching, and more continuing
      education in pain management than younger faculty. Younger nursing faculty
      remembered being taught pain management in nursing school and felt more
      adequately prepared than older nursing faculty. Faculty that reported practicing
      for longer periods of time felt less prepared in pain management than faculty who
      practiced for shorter periods of time. More continuing education in pain
      management may be needed for older nurses to meet the recommendations of the
      Institute of Medicines' report on relieving pain in the U.S. 

PMID- 24315277
TI  - A survey of conventional and complementary therapies used by youth with juvenile
      onset fibromyalgia.
AB  - Little is known regarding treatment choices of youth diagnosed with juvenile
      onset fibromyalgia (JFM) as they move into young adulthood. Additionally, there
      is little empirical evidence to guide youth with FM into appropriate treatment
      options, leading to a variety of therapies used to manage FM symptoms. The
      purpose of this descriptive study was to examine all therapies used by
      individuals with JFM as they entered young adulthood and the perceived
      effectiveness of these treatments. As part of a larger follow-up study,
      participants completed a web-based survey of all current and past treatments
      received for FM symptoms 2 years after their initial presentation and diagnosis
      at a pediatric rheumatology clinic. One hundred ten out of 118 eligible patients
      participated in the follow-up assessment as young adults (mean age 18.97 years;
      93.6% female). A majority of participants reported use of conventional
      medications (e.g., antidepressants, anticonvulsants) and nondrug therapies (e.g.,
      psychotherapy). Currently and within the past 2 years, antidepressant medications
      were the most commonly used to manage FM. Complementary treatments were used less
      often, with massage being the most popular choice. Although currently used
      treatments were reported as being effective, past treatments, especially
      medications, were viewed as being more variably effective. This is a potential
      reason why young adults with JFM might try more complementary and alternative
      approaches to managing their symptoms. More controlled studies are needed to
      investigate the effectiveness of these complementary methods to assist treatment
      providers in giving evidence-based treatment recommendations. 

PMID- 24315278
TI  - Description of behaviors in nonverbal critically ill patients with a traumatic
      brain injury when exposed to common procedures in the intensive care unit: a
      pilot study.
AB  - Behavioral indicators are strongly recommended for pain assessment in nonverbal
      patients. Although pain-related behaviors have been studied in critically ill
      patients, those with a traumatic brain injury (TBI) have been either excluded or
      underrepresented. Because these patients also likely experience pain, research is
      urgently needed to generate knowledge in this field. This pilot study aimed to
      explore pain-related behaviors of critically ill TBI patients when exposed to
      common procedures in the intensive care unit (ICU), using video recording at the
      bedside and a newly developed coding system. Ten TBI patients hospitalized in the
      ICU participated. A 44-item behavioral checklist created from existing tools was
      used as a coding system to identify behaviors before, during, and 20 minutes
      after a nociceptive procedure (turning) and a nonnociceptive procedure
      (noninvasive blood pressure [NIBP]). Patients were video recorded to check for
      interrater agreement between two trained observers. TBI patients exhibited more
      behaviors during turning than at rest or during NIBP (p < .001). The following
      behaviors were observed during turning: levator contraction (n = 7), frowning (n
      = 5), opening eyes (n = 5), weeping eyes (n = 5), raising eyebrows (n = 5),
      activating the ventilator alarms (n = 7), and muscle tension (n = 5). No change
      in behaviors was noted during NIBP. After educational training and using videos,
      the average percentage of agreement for observed behaviors between two trained
      research assistants was 96%. Pain in critically ill TBI patients can be
      detrimental to health and recovery. ICU clinicians should be aware of pain
      related behaviors to enable better detection and treatment in this highly
      vulnerable group. 

PMID- 24315279
TI  - Knowledge and attitudes regarding pain management of pediatric nurses in Turkey.
AB  - Nurses play an important role in managing children's pain. The nurse's accurate
      assessment, appropriate intervention, and evaluation of pain relief measures are
      necessary for positive patient outcomes. The aim of this study was to determine
      the level of knowledge and attitudes of pediatric nurses regarding the child's
      pain. The Pediatric Nurses' Knowledge and Attitude Survey (PNKAS) was used to
      evaluate the nurses' knowledge and attitudes. The PNKAS consists of 40 questions.
      In this study, 29.9% of nurses had a diploma and 40.6% associate's, 25.0%
      bachelor's, and 4.5% master's degree, and respondents had an everage 6.1 years
      pediatric nursing experience. The total mean score on the PNKAS scale was 38.2%.
      The highest score was 65%, and the lowest score 15%. The findings of the survey
      show that pediatric nurses in Turkey have insufficient knowledge regarding pain
      management and could benefit from additional education on that issue. 

PMID- 24315280
TI  - Management of the hospitalized patient experiencing acute on chronic pain: a case
      study.
AB  - The ability to balance the patient's level of comfort while minimizing adverse
      outcomes related to overdosing remains the key to providing excellent post
      operative care for the patient with chronic pain. This article presents the case
      of a hospitalized patient with severe pain and the challenges her care presented
      to the nursing staff. 

PMID- 24315281
TI  - Complementary therapies for osteoarthritis: are they effective?
AB  - Increasing interest has focused on complementary management modalities, including
      tai chi, acupuncture, yoga, and massage therapy, as treatments for osteoarthritis
      (OA). This review article synthesizes evidence from randomized controlled trials
      (RCTs) and systematic reviews (SRs) that examined one or more of the above as
      treatments for OA. Medline, Pubmed, and Cinahl databases were searched to
      identify English-language articles using an RCT design or that conducted a SR of
      published studies and presented data on symptom or functional outcomes. Two
      authors independently abstracted relevant information (e.g., study sample,
      intervention characteristics, treatment effects, safety data). Retained articles
      (n = 29) included those that evaluated tai chi (8 RCTs, 2 SRs), acupuncture (11
      RCTs, 4 SRs), yoga (2 RCTs), and massage therapy (2 RCTs). Available evidence
      indicates that tai chi, acupuncture, yoga, and massage therapy are safe for use
      by individuals with OA. Positive short-term (<=6 months) effects in the form of
      reduced pain and improved self-reported physical functioning were found for all 4
      treatments. Limited information exists regarding the relative effectiveness of
      the therapies (e.g., yoga vs. tai chi vs. acupuncture), as well as treatment
      effects in persons with joint involvement besides the knee and in distinct
      patient subgroups (e.g., older vs. younger adults, persons with mild vs. moderate
      vs. advanced disease). Complementary therapies can reduce pain and improve
      function in adults with OA. Research is needed to evaluate long-term benefits of
      the treatments, as well as their relative effects among diverse patient
      subgroups. 

PMID- 24315282
TI  - The use of oral sucrose for procedural pain relief in infants up to six months of
      age: a randomized controlled trial.
AB  - The aim of this study was to evaluate the effectiveness of oral sucrose in
      decreasing pain during minor procedures in infants of 1-6 months corrected age. A
      blinded randomized controlled trial with infants aged 4-26 weeks who underwent
      venipuncture, heel lance or intravenous cannulation were stratified by corrected
      age into > 4-12 weeks and > 12-26 weeks. They received 2 mL of either 25% sucrose
      or sterile water orally 2 minutes before the painful procedure. Nonnutritional
      sucking and parental comfort, provided in adherence to hospital guidelines, were
      recorded. Pain behavior was recorded using a validated 10 point scale at
      baseline, during and following the procedure. Data collectors were blinded to the
      intervention. A total of 21 and 20 infants received sucrose and water,
      respectively, in the > 4-12-week age group, and 21 and 22, respectively, in the >
      12-26-week age group. No statistical differences were found in pain scores
      between treatment and control groups at any data collection points in either age
      group. Infants aged > 4-12 weeks who did nonnutritional sucking showed
      statistically significantly lower median pain scores at 1, 2, and 3 minutes after
      the procedure than those who did not suck. Infants aged > 4-26 weeks exhibited
      pain behavior scores that indicated moderate to large pain during painful
      procedures; however, there was insufficient evidence to show that 2 mL 25%
      sucrose had a statistically significant effect in decreasing pain. Infants should
      be offered nonnutritional sucking in compliance with the Baby Friendly Health
      Initiative during painful procedures.

PMID- 24315283
TI  - Installation and performance testing of an XtRa-NaI(Tl) Compton Suppression
      System at the NED-NTUA.
AB  - This paper presents the Compton Suppression System, recently installed at the
      Nuclear Engineering Department of NTUA. The system consists of an XtRa Ge
      detector coupled with a NaI(Tl) guard detector. The electronic set-up allows for
      the simultaneous collection of both the suppressed and the unsuppressed spectra.
      System performance is investigated using certified point and volume sources.
      Parameters such as Peak Suppression Factors, peak-to-Compton ratios and minimum
      detectable activity for specific radionuclides are determined. 

PMID- 24315284
TI  - Proficiency test of 90Y and 89Sr activity measurements in Polish hospitals.
AB  - The Radioisotope Centre POLATOM organized a proficiency test of activity
      measurements of (90)Y and (89)Sr with nuclear medicine departments in Polish
      hospitals. Radioactive solutions used in this exercise were standardized by the
      TDCR method using the measurement systems of the National Standard of
      Radionuclides Activity in Poland. Results were analysed in compliance with
      ISO/IEC 17043:2010 (ISO, 2010) by calculating z scores and zeta (zeta) scores.
      The overall performance of the participants varied significantly. The sources of
      errors appeared to be the values of the calibration factor used during activity
      assay and the underestimation of uncertainties by the participants. 

PMID- 24315285
TI  - A long-term performance evaluation of the gamma-ray activity measurement
      laboratory in CPST, Lithuania.
AB  - The quality control procedures used for two HPGe detectors (a well-type and a
      GAMMA-X coaxial) are described. Since 2001, check sources containing (137)Cs have
      been measured weekly for 7200s each, and the gamma-ray spectrometry system
      background was determined once per month for an acquisition time of 100,000 s.
      The laboratory participated in the international comparisons at environmental
      radioactivity level organized by the IAEA, Riso National Laboratory and NPL.

PMID- 24315286
TI  - Straightening of curved pattern of collagen fibers under load controls aortic
      valve shape.
AB  - The network of collagen fibers in the aortic valve leaflet is believed to play an
      important role in the strength and durability of the valve. However, in addition
      to its stress-bearing role, such a fiber network has the potential to produce
      functionally important shape changes in the closed valve under pressure load. We
      measured the average pattern of the collagen network in porcine aortic valve
      leaflets after staining for collagen. We then used finite element simulation to
      explore how this collagen pattern influences the shape of the closed valve. We
      observed a curved or bent pattern, with collagen fibers angled downward from the
      commissures toward the center of the leaflet to form a pattern that is concave
      toward the leaflet free edge. Simulations showed that these curved fiber
      trajectories straighten under pressure load, leading to functionally important
      changes in closed valve shape. Relative to a pattern of straight collagen fibers
      running parallel to the leaflet free edge, the concave pattern of curved fibers
      produces a closed valve with a 40% increase in central leaflet coaptation height
      and with decreased leaflet billow, resulting in a more physiological closed valve
      shape. Furthermore, simulations show that these changes in loaded leaflet shape
      reflect changes in leaflet curvature due to modulation of in-plane membrane
      stress resulting from straightening of the curved fibers. This effect appears to
      play an important role in normal valve function and may have important
      implications for the design of prosthetic and tissue engineered replacement
      valves. 

PMID- 24315287
TI  - Accuracy and repeatability of joint angles measured using a single camera
      markerless motion capture system.
AB  - Markerless motion capture systems have developed in an effort to evaluate human
      movement in a natural setting. However, the accuracy and reliability of these
      systems remain understudied. Therefore, the goals of this study were to quantify
      the accuracy and repeatability of joint angles using a single camera markerless
      motion capture system and to compare the markerless system performance with that
      of a marker-based system. A jig was placed in multiple static postures with
      marker trajectories collected using a ten camera motion analysis system. Depth
      and color image data were simultaneously collected from a single Microsoft Kinect
      camera, which was subsequently used to calculate virtual marker trajectories. A
      digital inclinometer provided a measure of ground-truth for sagittal and frontal
      plane joint angles. Joint angles were calculated with marker data from both
      motion capture systems using successive body-fixed rotations. The sagittal and
      frontal plane joint angles calculated from the marker-based and markerless system
      agreed with inclinometer measurements by <0.5 degrees . The systems agreed with
      each other by <0.5 degrees  for sagittal and frontal plane joint angles and <2
      degrees  for transverse plane rotation. Both systems showed a coefficient of
      reliability <0.5 degrees  for all angles. These results illustrate the
      feasibility of a single camera markerless motion capture system to accurately
      measure lower extremity kinematics and provide a first step in using this
      technology to discern clinically relevant differences in the joint kinematics of
      patient populations. 

PMID- 24315288
TI  - Fracture mechanics of the femoral neck in a composite bone model: effects of
      platen geometry.
AB  - Load applicator (platen) geometry used for axial load to failure testing of the
      femoral neck varies between studies and the biomechanical consequences are
      unknown. The purpose of this study was to determine if load application with a
      flat versus a conical platen results in differing fracture mechanics. Femurs were
      aligned in 25 degrees  of adduction and an axial compressive force was applied to
      the femoral heads at a rate of 6 mm/min until failure. Load application with the
      conical platen resulted in an average ultimate failure load, stiffness, and
      energy to failure of 9067 N, 4033 N/mm, and 12.12 J, respectively. Load
      application with the flat platen resulted in a significant (p<0.05) reduction in
      ultimate failure load (7620 N) and stiffness (2924 N/mm). Energy to failure
      (12.30 J) was not significantly different (p=0.893). Different fracture patterns
      were observed for the two platens and the conical platen produced fractures more
      similar to clinical observations. Use of a flat platen underestimates the
      strength and stiffness of the femoral neck and inaccurately predicts the
      associated fracture pattern. These findings must be considered when interpreting
      the results of prior biomechanical studies on femoral neck fracture and for the
      development of future femoral neck fracture models.

PMID- 24315289
TI  - Mechanical properties of cancer cytoskeleton depend on actin filaments to
      microtubules content: investigating different grades of colon cancer cell lines.
AB  - Biomechanical properties of cancer cells have been proposed as promising
      biomarkers to investigate cancer progression. Cytoskeletal reorganization alters
      these characteristics in different grades of cancer cells. In the present study
      based on the micropipette aspiration method, whole body evaluation for two
      different colon cancer cells was performed to determine viscoelastic parameters
      of the cells. A finite element model was developed for verification of
      experiments and predicting some behaviors of cells. Western blot analysis and
      fluorescence intensity for actin microfilaments and microtubules were performed
      to measure cell content of the proteins. It was illustrated that the proportion
      of microtubules and actin microfilaments is different in grade I and grade IV
      colon cancer cells in a manner that microtubules attain an effectual role in
      progressive reorganization of cytoskeleton in transition from nonaggressive to
      malignant phenotypes in cancer cells. Furthermore, it was concluded that larger
      instantaneous Young's modulus value for high grade cells is related to the
      existence of extensively build-up actin networks at the cell cortex. Based on the
      cell mechanics results, a simple parameter is suggested for sorting different
      grades of colon cancer cells. 

PMID- 24315291
TI  - Visual acuity deficits in children with nystagmus and Down syndrome.
AB  - PURPOSE: To investigate the association between visual acuity deficits and
      fixation instability in children with Down syndrome and nystagmus. DESIGN:
      Prospective cross-sectional study. METHODS: setting: Institutional. study
      population:Sixteen children (aged 10 months-14 years) with Down syndrome and
      nystagmus, and a control group of 93 age-similar children with unassociated
      infantile nystagmus. observation procedures: Binocular Teller acuity card testing
      and eye-movement recordings. Fixation stability was quantified using the
      nystagmus optimal fixation function (NOFF). An exponential model based on results
      from the control group with unassociated infantile nystagmus was used to relate
      fixation stability to age-corrected visual acuity deficits. main outcome
      measures: Binocular grating visual acuity and NOFF. RESULTS: Visual acuity was
      0.2-0.9 logMAR (20/30-20/174 Snellen equivalent) and corresponded to a 0.4 logMAR
      (4 lines) mean age-corrected visual acuity deficit. Fixation stability ranged
      from poor to mildly affected. Although visual acuity deficit was on average 0.17
      logMAR larger (P = .005) than predicted by the model, most children had visual
      acuity deficit within the 95% predictive interval. CONCLUSIONS: There was a small
      mean difference between the measured visual acuity deficit and the prediction of
      the nystagmus model. Although other factors also contribute to visual acuity loss
      in Down syndrome, nystagmus alone could account for most of the visual acuity
      deficit in these children.

PMID- 24315290
TI  - Autoimmune retinopathy.
AB  - PURPOSE: To provide a detailed review of current clinical guidelines for the
      diagnosis, work-up and treatment of autoimmune retinopathy and to preview briefly
      possible future therapies. DESIGN: Perspective based on literature review and
      clinical expertise. METHODS: Interpretation of current literature, relying on the
      authors' clinical experience. RESULTS: Autoimmune retinopathy is a rare
      immunologic disease characterized by the presence of circulating antiretinal
      antibodies along with electroretinographic and visual field abnormalities. An
      ophthalmic examination can be normal or show minimal findings. The diagnosis of
      autoimmune retinopathy is made difficult by diagnostic criteria that are both
      limited and nonstandardized. Currently, the diagnosis is made based on the
      demonstration of serum antiretinal antibodies and the presence of clinical
      manifestations (including abnormal electroretinographic findings). The mere
      presence of these antibodies is not diagnostic. Lack of an accepted gold standard
      for antiretinal antibodies detection and poor interlaboratory concordance make
      the diagnosis challenging. There are anecdotal reports of immunosuppressive
      therapy in autoimmune retinopathy; however, the response to treatment is
      variable, with more favorable results achieved in paraneoplastic retinopathy,
      particularly cancer-associated retinopathy, with a combination of chemotherapy
      and immunosuppression. Whether an earlier attempt to treat nonparaneoplastic
      autoimmune retinopathy would be more beneficial is unknown. Early treatment
      attempts are limited by lack of sensitive and specific assays and definitive
      clinical criteria. CONCLUSIONS: Little is known about the clinical course,
      prognosis and treatment of autoimmune retinopathy. Additional studies should
      examine the specificity and pathogenicity of antiretinal antibodies and screen
      for biomarkers, and they should be conducted concurrently with studies seeking to
      identify appropriate treatment.

PMID- 24315292
TI  - Increased risk of Parkinson disease following a diagnosis of neovascular age
      related macular degeneration: a retrospective cohort study.
AB  - PURPOSE: To investigate the risk for Parkinson disease during a 3-year follow-up
      period after a diagnosis of neovascular age-related macular degeneration (AMD)
      using a nationwide population-based dataset in Taiwan. DESIGN: A retrospective
      matched-cohort study. METHODS: We identified 877subjects with neovascular AMD as
      the study cohort and randomly selected 8770 subjects for a comparison cohort.
      Each subject was individually followed for a 3-year period to identify those who
      subsequently developed Parkinson disease. Stratified Cox proportional hazard
      regressions were performed as a means of comparing the 3-year risk of subsequent
      Parkinson disease between the study and comparison cohorts. RESULTS: The
      incidence rate of Parkinson disease was 5.32 (95% confidence interval [CI]: 3.03
      8.72) per 1000 person-years in patients with neovascular AMD and 2.09 (95% CI:
      1.59-2.70) per 1000 person-years in comparison patients. The log-rank test
      indicated that subjects with neovascular AMD had a significantly lower 3-year
      Parkinson disease-free survival rate than comparison subjects (P < .001). After
      censoring cases in which patients died during the follow-up period and adjusting
      for monthly income, geographic region, hypertension, diabetes, hyperlipidemia,
      and coronary heart disease, the hazard ratio of Parkinson disease during the 3
      year follow-up period for subjects with neovascular AMD was 2.57 (95% CI: 1.42
      4.64) that of comparison subjects. CONCLUSION: In this study, subjects with
      neovascular AMD were found to be at a significant risk of Parkinson disease
      during a 3-year follow-up period after their diagnosis among Taiwanese Chinese.
      Further study is needed to confirm our findings and explore the underlying
      pathomechanism.

PMID- 24315293
TI  - Atropine for the treatment of childhood myopia: changes after stopping atropine
      0.01%, 0.1% and 0.5%.
AB  - PURPOSE: To study the change in spherical equivalent and other ocular parameters
      1 year after stopping the administration of atropine. DESIGN: Prospective
      randomized double-masked clinical trial. METHODS: We assigned 400 myopic
      children, 6 to 12 years of age, to receive atropine 0.5%, 0.1% or 0.01% for 24
      months, after which medication was stopped. Parents and children gave informed
      consent to participate in the research. Children were reviewed at 26, 32 and 36
      months, and changes in cycloplegic spherical equivalent (SE), axial length (AL),
      visual acuity, pupil size, and accommodation were assessed. RESULTS: Of the
      children, 356 (89%) entered into the washout phase. At entry, there was no
      significant difference in age, gender, SE, or AL among the children in the
      various atropine groups. Over the following 12 months, myopic progression was
      greater in the 0.5% eyes (-0.87 +/- 0.52 D), compared to the 0.1% (-0.68 +/- 0.45
      D) and 0.01% eyes (-0.28 +/- 0.33 D, P < 0.001). AL growth was also greater in
      the 0.5% (0.35 +/- 0.20 mm) and 0.1% (0.33 +/- 0.18 mm) eyes, compared to the
      0.01% eyes (0.19 +/- 0.13 mm, P < 0.001). Pupil size and near visual acuity
      returned to pre-atropine levels in all groups, but accommodation at 36 months was
      less in the 0.5% eyes (13.24 +/- 2.72 D) compared to the 0.1% (14.45 +/- 2.61 D)
      and 0.01% eyes (14.04 +/- 2.90 D, P < 0.001). The overall increase in SE over the
      entire 36 months in the 0.5%, 0.1% and 0.01% groups was -1.15 +/- 0.81 D, -1.04
      +/- 0.83 D and -0.72 +/- 0.72 D, respectively (P < 0.001). CONCLUSION: There was
      a myopic rebound after atropine was stopped, and it was greater in eyes that had
      received 0.5% and 0.1% atropine. The 0.01% atropine effect, however, was more
      modulated and sustained.

PMID- 24315295
TI  - Lack of polypoidal lesions in patients with myopic choroidal neovascularization
      as evaluated by indocyanine green angiography.
AB  - OBJECTIVE: To investigate the prevalence of polypoidal choroidal vasculopathy
      (PCV) in patients with myopic choroidal neovascularization (CNV) using
      indocyanine green angiography (ICGA). DESIGN: Retrospective cross-sectional
      study. METHODS: A total of 297 eyes (255 patients) who presented with treatment
      naive myopic CNV between January 2005 and December 2011 at Yonsei University
      Medical Center in Seoul, South Korea, were reviewed. Fluorescein angiography (FA)
      images obtained from the patients were analyzed to detect CNV presence and
      classify disease type. ICGA images were reviewed to detect polypoidal lesions.
      The main outcome measure was the prevalence of polypoidal lesions in patients
      with myopic CNV. RESULTS: All 297 eyes with myopic CNV were type 2 CNV, and mean
      age at diagnosis was 47.32 +/- 14.69 years. The mean refractive error was -11.95
      +/- 5.88 diopters, and the mean axial length was 29.39 +/- 2.02 mm in the
      affected eyes. Among the myopic CNV eyes, 141 eyes (118 patients) were older than
      50 years of age (mean 60.48 +/- 7.34 years). No eyes with myopic CNV showed
      polypoidal lesions on ICGA at initial presentation. After treatments for myopic
      CNV, 243 eyes (206 patients) completed at least 12 months of follow-up, and 86
      eyes (35.4%) showed at least one recurrence of CNV during follow-up. The follow
      up imaging studies, FA, and ICGA, showed no polypoidal lesions associated with
      recurred myopic CNV. CONCLUSIONS: ICGA analysis demonstrated no polypoidal
      component in myopic eyes with CNV.

PMID- 24315294
TI  - The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical
      outcomes of a randomized controlled trial.
AB  - PURPOSE: To determine whether topical corticosteroids as adjunctive therapy for
      bacterial keratitis improves long-term clinical outcomes. DESIGN: Randomized,
      placebo-controlled, double-masked clinical trial. METHODS: This multicenter trial
      compared 1.0% prednisolone sodium phosphate to placebo in the treatment of
      bacterial keratitis among 500 patients with culture-positive ulcers receiving 48
      hours of moxifloxacin before randomization. The primary endpoint was 3 months
      from enrollment, and 399 patients were evaluated at 12 months. The outcomes
      examined were best spectacle-corrected visual acuity (BSCVA) and scar size at 12
      months. Based on previous results, regression models with adjustments for
      baseline status and/or causative organism were used for analysis. RESULTS: No
      significant differences in clinical outcomes by treatment group were seen with
      the prespecified regression models (BSCVA: -0.04 logMAR, 95% CI, -0.12 to 0.05, P
      = .39; scar size: 0.03 mm, 95% CI, -0.12 to 0.18, P = .69). A regression model
      including a Nocardia-treatment arm interaction found corticosteroid use
      associated with a mean 1-line improvement in BSCVA at 12 months among patients
      with non-Nocardia ulcers (-0.10 logMAR, 95% CI, -0.19 to -0.02, P = .02). No
      significant difference was observed in 12-month BSCVA for Nocardia ulcers (0.18
      logMAR, 95% CI, -0.04 to 0.41, P = .16). Corticosteroids were associated with
      larger mean scar size at 12 months among Nocardia ulcers (0.47 mm, 95% CI, 0.06
      0.88, P = .02) and no significant difference was identified by treatment for scar
      size for non-Nocardia ulcers (-0.06 mm, 95% CI, -0.21 to 0.10, P = .46).
      CONCLUSIONS: Adjunctive topical corticosteroid therapy may be associated with
      improved long-term clinical outcomes in bacterial corneal ulcers not caused by
      Nocardia species.

PMID- 24315296
TI  - Distribution of retinal layer atrophy in patients with Parkinson disease and
      association with disease severity and duration.
AB  - PURPOSE: To evaluate the thickness of the 10 retinal layers in the paramacular
      area of Parkinson disease patients using a new segmentation technology of optical
      coherence tomography (OCT) to examine whether the thickness of specific layers
      predicts neurodegeneration or Parkinson disease severity. DESIGN: Observational
      prospective study. METHODS: Parkinson disease patients (n = 129) and age-matched
      healthy subjects (n = 129) were enrolled. The Spectralis OCT system was used to
      automatically segment all retinal layers in a parafoveal scan using the new
      segmentation application prototype. Mean thickness of each layer was calculated
      and compared between Parkinson disease patients and healthy subjects, and between
      Parkinson disease patients with disease durations of less than or at least 10
      years. A correlation analysis was performed to evaluate the association between
      retinal layer thickness, duration of disease, and Parkinson disease severity.
      Logistic regression analysis was performed to determine the most sensitive layer
      for predicting axonal atrophy. RESULTS: Parkinson disease patients showed
      statistically significant reduced thickness in the retinal nerve fiber, ganglion
      cell, inner plexiform, and outer plexiform layers and increased thickness in the
      inner nuclear layer compared with healthy subjects (P < .05). The inner retinal
      layers were more affected in Parkinson disease patients with long disease
      duration. The ganglion cell layer thickness was inversely correlated with disease
      duration and Parkinson disease severity, and was predictive of axonal damage in
      Parkinson disease patients. CONCLUSIONS: The segmentation application of the
      Spectralis OCT revealed retinal layer atrophy in Parkinson disease patients,
      especially in the inner layers of patients with long disease duration. Ganglion
      cell layer reduction was associated with increased axonal damage.

PMID- 24315298
TI  - [Nurses association as a determining force in the development of the nurse
      profession, a pending subject in Spanish Nursing].

PMID- 24315297
TI  - Tear meniscus dimensions in tear dysfunction and their correlation with clinical
      parameters.
AB  - PURPOSE: To evaluate relationships between tear meniscus dimensions and
      parameters of ocular surface disease in a variety of tear dysfunction conditions.
      DESIGN: Single-institution prospective observational study. METHODS: This study
      from the Baylor College of Medicine included 128 eyes of 64 subjects. Cross
      sectional lower tear meniscus height and tear meniscus area were measured using
      optical coherence tomography and were compared with tear break-up time (TBUT),
      corneal staining, conjunctival staining, and an irritation symptom questionnaire
      (Ocular Surface Disease Index). Study groups included meibomian gland disease
      (MGD), aqueous tear deficiency (ATD), Sjogren syndrome, non-Sjogren syndrome ATD,
      and control subjects. Statistical analyses were performed using the Pearson
      correlation and Student's t test. RESULTS: When compared with mean tear meniscus
      height in controls (345 MUm), mean tear meniscus height was lower in all tear
      dysfunction (234 MUm; P = .0057), ATD (210 MUm; P = .0016), and Sjogren syndrome
      groups (171 MUm; P = .0054). For tear meniscus height <=210 MUm, relative risk
      ratio for developing corneal staining >=10 was 4.65. Tear meniscus height
      correlated with corneal staining for all subjects (R = -0.32; P = .0008), MGD (R
      = +0.40; P = .059), and ATD (R = -0.36; P = .04). Tear meniscus area showed
      similar trends in MGD (R = +0.55; P = .006) and ATD (R = -0.40; P = .018). Tear
      meniscus height correlated with TBUT for all subjects (R = +0.39; P < .0001) and
      ATD (R = +0.37; P = .018). CONCLUSIONS: In tear dysfunction conditions, lower
      tear volume correlates with worse corneal epithelial disease in ATD and Sjogren
      syndrome, conditions with lacrimal gland dysfunction. In contrast, higher tear
      volume is associated with corneal epithelial disease in MGD. These findings may
      improve the ability to identify patients at risk for corneal epithelial disease.

PMID- 24315299
TI  - Lumbar spine side bending is reduced in end range extension compared to neutral
      and end range flexion postures.
AB  - Lumbar side bending movements coupled with extension or flexion is a known low
      back pain (LBP) risk factor in certain groups, for example, athletes
      participating in sports such as hockey, tennis, gymnastics, rowing and cricket.
      Previous research has shown that sagittal spinal postures influence the degree of
      spinal rotation, with less rotation demonstrated at end of range extension and
      flexion. To date it is unknown whether sagittal spinal postures influence side
      bending. The aim of this study was to determine whether side bend range of motion
      (ROM) of the lumbar spine is decreased in end-range flexion and extension
      postures compared to a neutral spine. Twenty subjects between 18 and 55 years of
      age [mean age = 22.8 yrs (6.8)] with no history of LBP were recruited for this
      study. Upper (L1-L3) and lower (L3-L5) lumbar side bend, were measured utilising
      a 14 camera system (Vicon, Oxford metrics, inc.) in end-range flexion, extension
      and neutral postures, in both sitting and standing positions. The results
      revealed no statistically significant difference in upper and lower lumbar side
      bend ROM in an end-range flexion posture compared to a neutral spinal posture. A
      reduction was found in the range of upper and lower lumbar side bend ROM in an
      end-range extended posture (p < 0.05), compared to neutral and end range flexion
      postures. This ROM reduction was found in sitting and standing. These findings
      allow clinicians to better interpret combined movements involving side bending of
      the lumbar spine in clinical and real life settings. 

PMID- 24315300
TI  - [Role of the hospital environment and equipment in the transmission of nosocomial
      infections].
AB  - The hospital environment is both a reservoir and source of infection for the
      hospital patient. Several areas around the patient should be considered: air,
      toilet water coming into contact with the patient, staff and medical devices,
      food, surfaces, and instruments contacting the patient's skin and mucosa, and
      sterile solutions. There are pathogens classically associated with each mode of
      transmission and environmental reservoir, but multi-resistant microorganisms have
      also been recently been associated with environmental acquisition. Protocols are
      currently available for the prevention of some classic environmental pathogens,
      as well as recommendations for the prevention of contamination in some
      procedures. However, these situations do not cover all forms of transmission, and
      most investigations of reservoirs or environmental sources are restricted to
      outbreak situations. 

PMID- 24315301
TI  - Outcomes after photoselective vaporization of the prostate and transurethral
      resection of the prostate in patients who develop prostatic obstruction after
      radiation therapy.
AB  - OBJECTIVE: To compare the need for repeat treatment or urinary diversion in
      patients undergoing transurethral resection of the prostate (TURP) compared with
      photoselective vaporization of the prostate (PVP) after brachytherapy or external
      beam radiation therapy (EBRT). METHODS: The prostate cancer database of Cleveland
      Clinic includes 3600 patients who have undergone prostate brachytherapy and 2500
      patients who have undergone EBRT. We cross-referenced these patients with the
      electronic medical record to identify patients who required PVP or TURP after
      radiation. The primary outcome was the need for any further intervention after
      PVP or TURP, including bladder neck incision, repeat TURP, or permanent
      supravesicular diversion. RESULTS: Sixty of the 3600 patients (1.7%) required
      prostate reduction surgery after brachytherapy. Of these 60 patients, 19 of 40
      (47.5%) who underwent TURP required further intervention, and 10 of 20 patients
      (50%) who underwent PVP required subsequent intervention. Twenty-eight of the
      2500 patients (1.1%) required prostate reduction surgery after EBRT. Of these 28
      patients, 5 of 18 patients (27.8%) who underwent TURP required further
      intervention, and 5 of 10 patients (50%) who underwent PVP required subsequent
      intervention. Following either type of radiation there was not a significant
      difference in the need for further treatment based on the type of surgery (P
      >.999 for brachytherapy; P = .412 for EBRT). The median time between radiation
      and prostate reduction surgery is 20.2 months (range, 14.6-27.6) after
      brachytherapy and 53.3 months (range, 27.5-53.3) after EBRT (P = .0005).
      CONCLUSION: This study suggests that PVP and TURP are comparable in treating
      prostatic obstruction after brachytherapy or EBRT. However, obstruction after
      brachytherapy occurs earlier compared with after EBRT.

PMID- 24315302
TI  - Editorial comment.

PMID- 24315303
TI  - Editorial comment.

PMID- 24315304
TI  - Does neoadjuvant androgen deprivation therapy before primary whole gland
      cryoablation of the prostate affect the outcome?
AB  - OBJECTIVE: To evaluate the effect of neoadjuvant androgen deprivation therapy
      (NADT) on the outcomes for primary whole gland prostate cryoablation (CRYO). NADT
      before CRYO has sometimes been used for prostate volume reduction, with some
      theoretical benefit toward improving disease control. NADT has been shown to be
      beneficial for biochemical disease-free survival (bDFS) with radiotherapy but not
      in conjunction with radical prostatectomy. METHODS: We retrospectively compared
      risk-stratified cohorts according to whether they had received NADT. bDFS was
      defined using the Phoenix criteria, and postoperative morbidity and complications
      were compared. RESULTS: A total of 1761 men had undergone NADT before CRYO and
      2727 had not. No differences were found in the incidence of postoperative
      incontinence, pad use, potency, or fistula formation. The rate of urinary
      retention at 12 months was slightly lower for those who had not undergone NADT
      (0.8% vs 1.2%, P = .015). No difference was found in bDFS between the NADT and
      non-NADT men (66.9% vs 66.5% at 5 years). When stratified by risk, however, a
      statistically significant difference was found between the NADT and non-NADT men
      only in the intermediate-risk cohort (71.3% vs 65.9%; P < .013). CONCLUSION: bDFS
      was statistically similar between the NADT and non-NADT men, except in the
      intermediate-risk cohort, with slightly improved survival for those undergoing
      NADT. No significant difference was found in the complication rates. These data
      do not support the routine use of NADT for men undergoing primary whole gland
      cryoablation, although its use could be considered for men with larger prostates
      or men in the intermediate-risk category.

PMID- 24315305
TI  - Relationship of chronic histologic prostatic inflammation in biopsy specimens
      with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men
      with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal
      examination.
AB  - OBJECTIVE: To investigate the relationship between serum [-2]proPSA (p2PSA) and
      derivatives with chronic histologic prostatic inflammation (CHPI) in men
      undergoing prostate biopsy for suspected prostate cancer (PCa). METHODS: This
      nested case-control study resulted from an observational prospective trial for
      the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and
      Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy,
      with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital
      rectal examination. CHPI was the outcome of interest and defined as the presence
      of moderate to large infiltration of lymphomononuclear cells with interstitial
      and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were
      considered the index tests and compared with the established biomarker reference
      standard tests: tPSA, fPSA, %fPSA. RESULTS: Of 267 patients subjected to prostate
      biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa
      patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and
      %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors
      of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the
      contrary, no significant differences were found in PSA, p2PSA, and derivatives
      between CHPI and benign prostatic hyperplasia (BPH) patients. CONCLUSION: Our
      findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from
      CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal
      digital rectal examination. p2PSA isoform and its derivatives could be useful in
      clinical decision making to avoid unnecessary biopsies in patients with CHPI and
      elevated tPSA value.

PMID- 24315306
TI  - Reply: To PMID 24315301.

PMID- 24315307
TI  - Evaluation of bladder clots using a nonsurgical treatment.
AB  - OBJECTIVE: To introduce a novel method to successfully evacuate severe clot
      retention in the bladder. METHODS: A total of 22 male patients were treated using
      our method for severe clot retention. The bladder was irrigated with 40,000 U
      chymotrypsin in 50 mL of 5% sodium bicarbonate using a Foley catheter (20 F-24 F)
      for 30 minutes. The clots were then easily mobilized and evacuated using
      continuous saline irrigation and suction with a 60-mL syringe. The procedure was
      repeated 2-4 times until all the blood clots had been evacuated. RESULTS: Of the
      22 patients, 19 were successfully treated using this method, with clot retention
      thoroughly resolved. CONCLUSION: The chymotrypsin and sodium bicarbonate
      irrigation technique is safe, inexpensive, and a successful method to evacuate
      severe clot retention.

PMID- 24315308
TI  - Place of ultrasonography in predicting vesicoureteral reflux in patients with
      mild renal scarring.
AB  - OBJECTIVE: To evaluate the role of renal ultrasonography (USG) in predicting
      vesicoureteral reflux (VUR) in children with mild renal scarring determined by
      dimercaptosuccinic acid scintigraphy performed after attack of urinary tract
      infections (UTI). METHODS: Dimercaptosuccinic acid scintigraphy, voiding
      cystourethrography (VCUG), and renal USG findings were evaluated retrospectively
      in children with UTI. Each kidney was evaluated as a separate renal unit (RU).
      RUs with severe scarring were excluded from the study. RUs having mild scarring
      with and without abnormal USG findings (group 1 and group 2, respectively) were
      compared in terms of the presence of VUR. RESULTS: There were a total of 228
      patients (70 men, mean age 47.06 +/- 44.14 months) and 456 RUs. Of the 185 RUs
      with mild scarring, 55 had abnormal USG findings (group 1), whereas 130 had
      normal USG findings (group 2). The rates of VUR and severe VUR (>=grade 4) were
      higher in group 1 compared with group 2 (69% vs 43%, P = .001 and 35% vs 7%
      respectively, P <.001). The sensitivity, specificity, positive predictive value,
      negative predictive value, and odds ratio of USG findings in predicting VUR in RU
      with mild scarring were 68%, 80%, 38%, 93%, and 8.2, respectively. CONCLUSION:
      Normal renal USG findings exclude a diagnosis of high-grade VUR to a large extend
      in children with UTI and mild renal scarring. Refraining from invasive VCUG might
      be a reasonable approach in these patients provided that no other predisposing
      factors for UTI and/or renal scarring present.

PMID- 24315309
TI  - Enhanced antitumor efficacy of integrin-targeted oncolytic adenovirus AxdAdB3
      F/RGD on bladder cancer.
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of AxdAdB-3 with Arg-Gly-Asp
      (RGD)-fiber modification (AxdAdB3-F/RGD), which enables integrin-dependent
      infection in bladder cancers. METHODS: Flow cytometric analysis was applied to
      evaluated adenovirus-mediated gene transduction into various cells. The
      cytopathic effects of AxdAdB3-F/RGD were evaluated in bladder cancer cell lines
      and a normal bladder mucosa-derived cell line (HCV29) with AxCAZ3-F/RGD (control)
      or AxdAdB-3. The efficacy of bladder instillation therapy with AxdAdB3-F/RGD for
      orthotopic bladder cancer was investigated in nude mice. RESULTS: Expression of
      coxsackievirus adenovirus receptor (CAR) and integrins (alphavbeta3 and
      alphavbeta5) vary in different bladder cancer cell lines. The susceptibility of
      various cell lines to adenovirus was associated with the expression of CAR.
      AxdAdB-3 was more cytopathic in CAR-positive bladder cancer cells than in CAR
      negative cells, whereas AxdAdB3-F/RGD caused effective oncolysis in both CAR
      positive and CAR-negative bladder cancer cells. AxdAdB3-F/RGD was not cytotoxic
      to HCV29 cells. Direct instillation of AxdAdB3-F/RGD into the bladder of the
      orthotopic model, established by CAR-deficient human bladder cancer cells,
      inhibited tumor growth and led to significantly elongated survival. CONCLUSION:
      E1A and E1B double-restricted oncolytic adenovirus with RGD fiber modification
      has enhanced infectivity and oncolytic effects to CAR-deficient bladder cancers,
      suggesting the therapeutic potential of AxdAdB3-F/RGD for bladder cancers.

PMID- 24315310
TI  - Matched comparison of robotic vs laparoscopic nephroureterectomy: an initial
      experience.
AB  - OBJECTIVE: To compare our initial robotic-assisted nephroureterectomy (RAN)
      experience with a well-established practice of performing laparoscopic
      nephroureterectomy (LN) to treat upper tract urothelial carcinoma (UTUC).
      METHODS: We reviewed our prospectively maintained minimally invasive surgery
      database. Patients who underwent RAN from April 2009 to December 2011 were
      matched by pathologic tumor stage and age (+/- 10 years) to those who underwent
      LN. RESULTS: Twenty-two matched pairs were evaluated. Mean operative time (298 vs
      251 minutes) and estimated blood loss (EBL, 380 vs 233 mL) were significantly
      higher for RAN, with a greater need for transfusion in this group. Complication
      rates were similar. The RAN group trended toward more frequent lymph node
      dissection and greater median node count when lymph node dissection was performed
      (59% vs 27% [P = .07] and 5.5 vs 1.0 [P = .13]). After a median follow-up of 10
      months for RAN and 15 months for LN, no significant difference was seen in the
      rate of bladder (36% vs 37%) or distant (32% vs 23%) recurrence, with similar
      median time to any recurrence (9 months vs 4 months, P = .32). CONCLUSION: RAN
      was associated with higher operative time and blood loss likely because of more
      frequent use of node dissection, robot repositioning, and technical inexperience.
      Lymph node dissection was more frequently performed with RAN, which reflects
      surgeon practice patterns. When a lymph node dissection was performed, the median
      node count was greater with RAN. Our initial experience with RAN suggests that
      this is an acceptable approach for the management of UTUC.

PMID- 24315311
TI  - Primary cryosurgery for clinically localized prostate cancer--do perioperative
      tumor characteristics correlate with post-treatment biopsy results?
AB  - OBJECTIVE: To investigate the rate and predictive factors of positive post
      treatment biopsy in men treated with primary cryosurgery for localized prostate
      cancer. METHODS: A retrospective review was performed of all patients treated
      with primary cryosurgery at a single institution between 1999 and 2012.
      Perioperative prostate-specific antigen (PSA) levels, Gleason score, and number
      of positive preoperative biopsy cores were obtained and correlated with
      postoperative biopsy results. Patients were stratified according to the risk
      classification system of D'Amico to low-, intermediate-, or high-risk groups.
      RESULTS: Sixty-five men were treated with primary cryosurgery, and 57 of 65 (88%)
      of them underwent postoperative biopsy on average 9 months after the treatment.
      Eleven of 57 patients (19%) were found to have persistent tumor on post-treatment
      biopsy. Men who had positive biopsy had significantly higher perioperative PSA
      levels than men who had negative biopsy (preoperative PSA 12.5 vs 6.2, P = .002;
      post-operative PSA nadir 4.3 vs 0.71, P = .005); however, no independent
      predictor was found on a multivariate analysis. Gleason score and number of
      positive preoperative biopsy cores did not predict tumor persistence. Positive
      biopsy results were found more often in the intermediate- and high-risk patients,
      although this was not statistically significant (low risk 9%, intermediate risk
      20%, and high risk 27%). CONCLUSION: Perioperative PSA levels, Gleason score, or
      number of positive pretreatment biopsy cores do not predict failure after primary
      cryosurgery for clinically localized prostate cancer. Our findings suggest that
      physicians, who offer primary cryosurgery to patients with localized prostate
      cancer, should consider offering post-treatment biopsy to patients to assure
      adequate cancer control.

PMID- 24315312
TI  - Is thermography useful for assessment of postoperative inflammation after
      surgical removal of mandibular third molars when methylprednisolone is
      administered and how does it correlate with patients' perception of swelling?
AB  - PURPOSE: To assess the differences in facial skin temperature after mandibular
      third molar removal when patients received methylprednisolone and placebo,
      respectively and to assess the correlation between patient-reported swelling
      using a visual analog scale (VAS) and facial skin temperature measured using
      thermography. PATIENTS AND METHODS: The study involved patients with 2 mandibular
      third molars with an indication for removal. The patients received either
      methylprednisolone or placebo in a randomized, crossover study design.
      Thermograms and the swelling VAS score were recorded 2 days after surgery. The
      outcome variable was the temperature difference (Deltat) between the operated and
      control sides. A 2-sample t test analyzed the difference in Deltat between the
      first and second operations. Spearman's rank correlation analysis was used to
      assess the correlation between the swelling VAS scores and the Deltat. RESULTS: A
      total of 124 patients (67 males, 57 females, mean age 25 years) had both
      mandibular third molars removed on 2 separate occasions. No difference in Deltat
      was found when methylprednisolone and placebo were given (P = .07). In addition,
      the correlation between the swelling VAS score and Deltat was 0.30 (P = .001) and
      0.09 (P = .3) after the first and second operation, respectively. CONCLUSIONS:
      Thermography does not seem sensitive enough to detect differences in the
      inflammatory response when patients received methylprednisolone or placebo. The
      correlation between the Deltat and patient-reported swelling was low (<=0.3).

PMID- 24315313
TI  - In vitro activity of tigecycline and comparators against Gram-positive and Gram
      negative isolates collected from the Middle East and Africa between 2004 and
      2011.
AB  - The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was established in
      2004 to monitor longitudinal changes in bacterial susceptibility to numerous
      antimicrobial agents, specifically tigecycline. In this study, susceptibility
      among Gram-positive and Gram-negative isolates between 2004 and 2011 from the
      Middle East and Africa was examined. Antimicrobial susceptibilities were
      determined using Clinical and Laboratory Standards Institute (CLSI) interpretive
      criteria, and minimum inhibitory concentrations (MICs) were determined by broth
      microdilution methods. US Food and Drug Administration (FDA)-approved breakpoints
      were used for tigecycline. In total, 2967 Gram-positive and 6322 Gram-negative
      isolates were examined from 33 participating centres. All Staphylococcus aureus
      isolates, including meticillin-resistant S. aureus, were susceptible to
      tigecycline, linezolid and vancomycin. Vancomycin, linezolid, tigecycline and
      levofloxacin were highly active (>97.6% susceptibility) against Streptococcus
      pneumoniae, including penicillin-non-susceptible strains. All Enterococcus
      faecium isolates were susceptible to tigecycline and linezolid, including 32
      vancomycin-resistant isolates. Extended-spectrum beta-lactamases were produced by
      16.6% of Escherichia coli and 32.9% of Klebsiella pneumoniae. More than 95% of E.
      coli and Enterobacter spp. were susceptible to amikacin, tigecycline, imipenem
      and meropenem. The most active agents against Pseudomonas aeruginosa and
      Acinetobacter baumannii were amikacin (88.0% susceptible) and minocycline (64.2%
      susceptible), respectively; the MIC90 (MIC required to inhibit 90% of the
      isolates) of tigecycline against A. baumannii was low at 2mg/L. Tigecycline and
      carbapenem agents were highly active against most Gram-negative pathogens.
      Tigecycline, linezolid and vancomycin showed good activity against most Gram
      positive pathogens from the Middle East and Africa. 

PMID- 24315314
TI  - Cerebral aspergillosis in adult critically ill patients: a descriptive report of
      10 patients from the AspICU cohort.
AB  - An unexpectedly high incidence of invasive pulmonary aspergillosis (IPA) has been
      reported in non-neutropenic intensive care unit (ICU) patients. After the
      respiratory tract, the brain is most often affected by invasive aspergillosis.
      However, little is known about brain involvement by Aspergillus in critically ill
      patients. In this study, demographics, risk profile, diagnosis, treatment and
      outcome of proven cases of invasive cerebral aspergillosis (ICA) taken from a
      cohort of 563 adult patients with evidenced Aspergillus involvement during their
      ICU stay were reviewed. Ten patients with central nervous system aspergillosis
      were identified. All had one or more host factors predisposing for invasive
      aspergillosis. The clinical and radiological presentation was non-specific and
      exclusively pulmonary-related. All but one patient had proven or
      probable/putative IPA. On cerebral computed tomography, lesions appeared as
      either solitary and hyperdense or were multiple and randomly distributed
      throughout the brain. One patient presented with sole meningeal infestation.
      Aspergillus infection was confirmed by brain biopsy in three subjects.
      Voriconazole was used as primary treatment in only one-half of the patients.
      Mortality was 90%. ICA is not frequently observed in adult ICU patients.
      Diagnosis must be considered in patients at risk presenting with proven or
      probable/putative IPA in association with suggestive neuroradiological findings.
      The brain is most likely affected through haematogenous dissemination from the
      lungs. Current treatment recommendations are not always applied and outcome
      remains dismal. 

PMID- 24315315
TI  - Four years data of raltegravir-based salvage therapy in HIV-1-infected, treatment
      experienced patients: the SALIR-E Study.
AB  - Apart from the BENCHMRK study, there are no large observational experiences
      describing the long-term efficacy and safety of rescue regimens for human
      immunodeficiency virus type 1 (HIV-1) infection. Antiretroviral-experienced
      patients with detectable viraemia starting a raltegravir (RAL)-based regimen
      between March 2007 and June 2009 were consecutively enrolled and followed for >=4
      years. Data were censored at Week 206 for homogeneity. Of 333 patients, 258
      (77.5%) were still on RAL-based therapy at Week 206, and 241 had undetectable HIV
      1 RNA (73% in intention-to-treat analysis). Of the 75 subjects who discontinued
      RAL therapy, 36 were lost to follow-up, 15 changed their regimen due to
      virological failure, 2 simplified their regimen stopping RAL, 9 stopped all
      antiretrovirals and 13 died. Overall, 100 subjects (30.0%) had at least one
      detectable viraemia, but only 32 (9.6%) had true viral failure. Seventeen
      patients continued their failing regimen. 'Blips' were experienced by 53 patients
      (15.9%), whilst 15 (4.5%) had confirmed viral rebound due to adherence issues and
      were re-suppressed upon treatment re-introduction. In a multivariate analysis of
      predictors of interruption or failure, each baseline HIV-1 RNA log10 increase was
      associated with an adjusted hazard ratio for failure of 1.6; having more than 13
      previous treatment courses also emerged as a predictor. Overall, adverse events
      were rare (n=64), with 13 deaths. Tumours were mainly early events, often fatal
      (7/15), mainly non-Hodgkin's lymphomas (8), followed by hepatocarcinoma (2). RAL
      proved effective and well tolerated in this cohort, and few patients experienced
      viral failure after 4 years. 

PMID- 24315316
TI  - Time-dependent hardening of blood clots quantitatively measured in vivo with
      shear-wave ultrasound imaging in a rabbit model of venous thrombosis.
AB  - OBJECTIVE: Provide in vivo blood clot hardening evolution with ultrasound using
      supersonic imaging of shear waves. METHODS: We conducted a prospective study in
      flow stasis-induced venous thrombosis within jugular veins of white female New
      Zealand rabbits. Blood clot elasticity was noninvasively measured in vivo using
      the Young's modulus (in kilopascals), on a 2-hour and a 2-week periods after
      thrombus induction. Monitoring was followed by a necropsy and ex vivo mechanical
      characterization to validate the existence and elasticity of explanted thrombi.
      RESULTS: Stagnant blood in the region of interest underwent clotting and
      progressive hardening with thrombus aging. The mean Young's moduli varied from
      1.0 +/- 0.6 kPa (at 10 min) to 5.3 +/- 1.6 kPa (at 2 hours), then to 25.0 +/- 6.8
      kPa (at 14 days) post-surgery. Mean ex vivo moduli of 6.2 +/- 0.7 kPa at 2 hours
      and 29.0 +/- 2.4 kPa at 2 weeks agreed with in vivo measures. CONCLUSIONS:
      Supersonic imaging of shear waves provides consistent quantitative non-invasive
      elasticity measurements not available with standard compression ultrasound
      imaging for diagnosing and following venous thromboembolism. This information
      translatable to humans could aid in determining whether continued anticoagulant
      treatment is necessary, especially in the setting of unprovoked venous
      thromboembolism.

PMID- 24315317
TI  - Investigation of CYP2C19 allele and genotype frequencies in Iranian population
      using experimental and computational approaches.
AB  - CytochromeP4502C19 is a genetically polymorphic gene with prominent role in drug
      metabolism. Regarding its critical medical importance, this study was conducted
      to achieve accurate CYP2C19allele frequencies in Iranian population and hereby
      paving the way for a tailor-made CYP2C19 DNA test. Iran is a large multi-ethnic
      country, however, its population structure for CYP2C19 alleles is calculated as
      nearly zero (Fwc (st)=0.001). The Study was conducted on 691 individuals in
      Tehran, the conurbation in which total population structure is significantly
      eroded by massive immigration and DNA was analyzed by TaqMan SNP genotyping
      assay. A cumulative meta-analysis was then conducted to achieve less than five
      percent variation range in allele frequencies with 99.9% confidence level. High
      degree of Hardy-Weinberg equilibrium in pooled data proved the authenticity of
      meta-analysis. By cumulative meta-analysis the average frequencies of CYP2C19*2
      and CYP2C19*3 alleles were calculated as 0.125[99.9% CI, 0.112-0.139] and
      0.006[99.9% CI, 0.004-0.009], respectively. According to the solid frequency data
      obtained by pooling the data and meta-analysis and comparing with other
      ethnicities, Iranian population's CYP2C19 allele frequencies completely differ
      from other Asian ethnicities and matches African and European ethnicities the
      most. Since this is the biggest CYP2C19 allele frequency study in the Middle
      East, the results of this study will also be useful in cross-population and
      regional CYP2C19 genetic variation studies. 

PMID- 24315318
TI  - Complete prekallikrein deficiency masquerading as a lupus anticoagulant.

PMID- 24315319
TI  - Unbalance between plasma levels of Protein Z and protein Z-dependent inhibitor in
      patients with colorectal and pancreatic cancer: a pilot study.

PMID- 24315320
TI  - Assessment of accuracy of genomic prediction for French Lacaune dairy sheep.
AB  - Genomic selection in Lacaune dairy sheep was investigated based on genotypes from
      the OvineSNP50 BeadChip (Illumina Inc., San Diego, CA). Historical artificial
      insemination progeny-tested rams formed a population of 2,892 genotyped rams.
      Additional ungenotyped rams and females were included by single-step genomic BLUP
      (ssGBLUP). Three prediction strategies were tried: pseudo-BLUP (using all rams
      and daughter yield deviations), pseudo-ssGBLUP (using all rams and daughter yield
      deviations), and regular ssGBLUP (using all phenotypes and pedigree in an animal
      model). The population linkage disequilibrium was determined, with an average
      squared correlation coefficient of 0.11 for markers closer than 0.1cM (lower than
      in dairy cattle). The estimated effective population is 370 individuals. Gain in
      accuracy of genomic selection over parent averages ranged from 0.10 to 0.20.
      Highest accuracies and lowest bias were found using regular ssGBLUP. Transition
      to a genomic breeding scheme is possible but costs need to be carefully
      evaluated. 

PMID- 24315321
TI  - Technical note: Selecting the best references in gene expression experiments in
      liver of cows receiving glucogenic supplements during the transition period.
AB  - Measuring gene expression is a commonly used method to monitor the reaction of
      cells and tissues to changing nutritional or physiological conditions. Selection
      of appropriate reference genes is a crucial point in gene expression experiments
      using real-time PCR techniques. Expression of the "ideal" reference gene should
      not be affected by the experimental treatments or physiological state of the
      tissue, organ, or the whole organism. Many programs are available from which to
      choose the most stable reference gene. In this study, 4 algorithms--DeltaCt,
      BestKeeper, NormFinder, and geNorm--were used to assess the expression stability
      of 5 candidate reference genes: beta-actin (ACTB), glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), ribosomal protein S9 (RPS9), ribosomal protein L32
      (RPL32), and TATA-box-binding protein (TBP), for use in an experiment aimed at
      measuring gene expression in the liver of cows fed glucogenic supplements in the
      transition from pregnancy to lactation. The results demonstrated that RPS9 and
      RPL32 were the most stably expressed in the liver under the conditions of the
      present experiment; the least stably expressed was ACTB.

PMID- 24315322
TI  - Oral administration of cobalt acetate alters milk fatty acid composition,
      consistent with an inhibition of stearoyl-coenzyme A desaturase in lactating
      ewes.
AB  - Previous investigations have shown that cobalt (Co) modifies milk fat composition
      in cattle, consistent with an inhibition of stearoyl-coenzyme A desaturase (SCD)
      activity, but it remains unclear whether other ruminant species are also
      affected. The present study examined the effects of oral administration of Co
      acetate on intake, rumen function, and milk production and fatty acid (FA)
      composition in sheep. Twenty lactating Assaf ewes were allocated into 1 of 4
      groups and used in a continuous randomized block design that involved a 15-d
      adaptation, a 6-d treatment, and a 10-d posttreatment period. During the
      treatment period, animals received an oral drench supplying 0 (control), 3 (Co3),
      6 (Co6), and 9 (Co9) mg of Co/kg of BW per day, administered in 3 equal doses at
      8-h intervals. Cobalt acetate had no influence on intake or milk fat and protein
      concentrations, whereas treatments Co6 and Co9 tended to lower milk yield.
      Results on rumen parameters showed no effects on rumen fermentation, FA
      composition, or bacterial community structure. Administration of Co acetate
      decreased milk concentrations of FA containing a cis-9 double bond and SCD
      product:substrate ratios, consistent with an inhibition of SCD activity in the
      ovine mammary gland. Temporal changes in milk fat composition indicated that the
      effects of treatments were evident within 3d of dosing, with further changes
      being apparent after 6d and reverting to pretreatment values by d 6 after
      administration. Effect on milk FA composition did not differ substantially in
      response to incremental doses of Co acetate. On average, Co decreased milk cis-9
      10:1/10:0, cis-9 12:1/12:0, cis-9 14:1/14:0, cis-9 16:1/16:0, cis-9 17:1/17:0,
      cis-9 18:1/18:0, and cis-9,trans-11 18:2/trans-11 18:1 concentration ratios by
      30, 32, 38, 33, 21, 24, and 25%, respectively. Changes in milk fat cis-9 10:1,
      cis-9 12:1, and cis-9 14:1 concentrations to Co treatment indicated that 51% of
      cis-9 18:1 and cis-9,trans-11 18:2 secreted in milk originated from Delta(9)
      desaturation. In conclusion, results demonstrated the potential of oral Co
      administration for the estimation of endogenous synthesis of FA containing a cis
      9 double bond in the mammary gland of lactating ruminants. Indirect comparisons
      suggest that the effects of Co differ between sheep and cattle. 

PMID- 24315323
TI  - Fine mapping of a quantitative trait locus for bovine milk fat composition on Bos
      taurus autosome 19.
AB  - A major quantitative trait locus (QTL) for milk fat content and fatty acids in
      both milk and adipose tissue has been detected on Bos taurus autosome 19 (BTA19)
      in several cattle breeds. The objective of this study was to refine the location
      of the QTL on BTA19 for bovine milk fat composition using a denser set of
      markers. Opportunities for fine mapping were provided by imputation from 50,000
      genotyped single nucleotide polymorphisms (SNP) toward a high-density SNP panel
      with up to 777,000 SNP. The QTL region was narrowed down to a linkage
      disequilibrium block formed by 22 SNP covering 85,007 bp, from 51,303,322 to
      51,388,329 bp on BTA19. This linkage disequilibrium block contained 2 genes:
      coiled-coil domain containing 57 (CCDC57) and fatty acid synthase (FASN). The
      gene CCDC57 is minimally characterized and has not been associated with bovine
      milk fat previously, but is expressed in the mammary gland. The gene FASN has
      been associated with bovine milk fat and fat in adipose tissue before. This gene
      is a likely candidate for the QTL on BTA19 because of its involvement in de novo
      fat synthesis. Future studies using sequence data of both CCDC57 and FASN, and
      eventually functional studies, will have to be pursued to assign the causal
      variant(s). 

PMID- 24315324
TI  - Short communication: Effects of molasses supplementation on performance of
      lactating cows fed high-alfalfa silage diets.
AB  - Twelve Holstein cows were used in a replicated Latin square experiment to
      determine the effect of adding dried molasses to high-alfalfa silage diets on
      dairy cow performance. Three isonitrogenous diets were formulated with a 68:32
      forage:concentrate ratio, with alfalfa silage as the only forage source. Dietary
      treatments were a control diet with no added molasses and 3 and 6% dried molasses
      diets. Three lactating Holstein cows fitted with ruminal cannulas were used to
      determine the effects of dietary treatments on ruminal fermentation. Dietary
      treatments had no effect on dry matter (average 23.3 kg/d), crude protein
      (average 4.4 kg/d), or neutral detergent fiber (average 7.4 kg/d) intake. Milk
      yield, energy-corrected milk (average 35.4 kg/d), and 4% fat-corrected milk
      (average 33.8 kg/d) were not influenced by dietary treatments. Cows fed the
      control diet produced milk with less milk urea nitrogen concentration than those
      fed molasses-supplemented diets. Ruminal pH, NH3-N concentration, and total
      volatile fatty acids were not different among dietary treatments. The molar
      proportion of acetate linearly increased, whereas the molar proportion of
      propionate linearly decreased as the level of dried molasses increased. It was
      concluded that addition of dried molasses to high-alfalfa silage diets at 6% of
      the diet (dry matter basis) increased milk urea nitrogen but had no effect on
      animal performance.

PMID- 24315325
TI  - Factors associated with age at slaughter and carcass weight, price, and value of
      dairy cull cows.
AB  - The sale of cull cows contributes to the overall profit of dairy herds. The
      objective of this study was to quantify the factors associated with slaughter age
      (mo), cow carcass weight (kg), price (?/kg of carcass weight), and value (?/head)
      of dairy cull cows. Data included 20,995 slaughter records in the period from
      2003 to 2011 of 5 different breeds: 2 dairy [Holstein Friesian (HF) and Brown
      Swiss (BS)] and 3 dual-purpose [Simmental (Si), Alpine Grey (AG), and Rendena
      (Re)]. Associations of breed, age of cow (except when the dependent variable was
      slaughter age), and year and month of slaughter with slaughter age, carcass
      weight, price, and value were quantified using a mixed linear model; herd was
      included as a random effect. The seasonal trends in cow price and value traits
      were inversely related to the number of cows slaughtered, whereas annual
      variation in external factors affected market conditions. Relative to BS cows, HF
      cows were younger at slaughter (73.1 vs. 80.7 mo), yielded slightly lighter
      carcasses (242 vs. 246 kg), and received a slightly lower price (1.69 vs. 1.73
      ?/kg) and total value (394 vs. 417 ?/head). Dual-purpose breeds were older and
      heavier and received a much greater price and total value at slaughter (521, 516,
      and 549 ?/head, respectively for Si, Re, and AG) than either dairy breed. Of the
      dual-purpose cows, Si carcasses were heavier (271 kg), whereas the carcasses of
      local breeds received a higher price (2.05 and 2.18 ?/kg for Re and AG,
      respectively) and Alpine Grey cows were the oldest at slaughter (93.3 mo). The
      price per kilogram of cull cow carcasses was greatest for very young cows (i.e.,
      <3 yr of age) and the differential in price and value between younger and older
      cows was greater in dual-purpose than in dairy breeds. Large differences in cull
      cow whole carcass value (carcass weight * unit price) among dairy breeds suggest
      that such a trait could be considered in the breeding objectives of the breeds.

PMID- 24315326
TI  - [Deciding despite uncertainty].

PMID- 24315327
TI  - When is enough evidence enough? - Using systematic decision analysis and value-of
      information analysis to determine the need for further evidence.
AB  - Decision analysis (DA) and value-of-information (VOI) analysis provide a
      systematic, quantitative methodological framework that explicitly considers the
      uncertainty surrounding the currently available evidence to guide healthcare
      decisions. In medical decision making under uncertainty, there are two
      fundamental questions: 1) What decision should be made now given the best
      available evidence (and its uncertainty)?; 2) Subsequent to the current decision
      and given the magnitude of the remaining uncertainty, should we gather further
      evidence (i.e., perform additional studies), and if yes, which studies should be
      undertaken (e.g., efficacy, side effects, quality of life, costs), and what
      sample sizes are needed? Using the currently best available evidence, VoI
      analysis focuses on the likelihood of making a wrong decision if the new
      intervention is adopted. The value of performing further studies and gathering
      additional evidence is based on the extent to which the additional information
      will reduce this uncertainty. A quantitative framework allows for the valuation
      of the additional information that is generated by further research, and
      considers the decision maker's objectives and resource constraints. Claxton et
      al. summarise: "Value of information analysis can be used to inform a range of
      policy questions including whether a new technology should be approved based on
      existing evidence, whether it should be approved but additional research
      conducted or whether approval should be withheld until the additional evidence
      becomes available." [Claxton K. Value of information entry in Encyclopaedia of
      Health Economics, Elsevier, forthcoming 2014.] The purpose of this tutorial is to
      introduce the framework of systematic VoI analysis to guide further research. In
      our tutorial article, we explain the theoretical foundations and practical
      methods of decision analysis and value-of-information analysis. To illustrate, we
      use a simple case example of a foot ulcer (e.g., with diabetes) as well as key
      references from the literature, including examples for the use of the decision
      analytic VoI framework by health technology assessment agencies to guide further
      research. These concepts may guide stakeholders involved or interested in how to
      determine whether or not and, if so, which additional evidence is needed to make
      decisions. 

PMID- 24315328
TI  - [Diagnosis in context - broadening the perspective].
AB  - In a primary care setting the diagnostic process typically starts with a symptom
      or sign reported by the patient. Primary care physicians face the challenge to
      consider a broad spectrum of possible aetiologies or differential diagnoses when
      choosing appropriate diagnostic tests. The classical diagnostic cross-sectional
      study investigates the accuracy of a diagnostic test or a combination of several
      tests in regard to just one target disease. The complexity facing the clinician
      remains unconsidered or is being split and presented in several parts which the
      clinician has to combine. In this paper we suggest a design for diagnostic
      studies that considers the requirements of diagnosis in primary care more
      comprehensively: the comprehensive diagnostic study. The essential characteristic
      of the design is the simultaneous consideration of the whole spectrum of relevant
      aetiologies when evaluating several diagnostic tests. We present single
      characteristics and specific features of this design in regard to research
      question, study sampling, index test, reference standard and analysis, and
      illustrate them using the example of a study investigating chest pain in primary
      care. 

PMID- 24315329
TI  - [Overviews - status quo, potentials and perspectives].
AB  - The increase in scientific literature has led reviewers to conduct overviews,
      hereby creating a new publication type. Overviews of reviews may have several
      advantages. For example, they can be conducted in a shorter time frame, they
      offer the opportunity of providing decision makers with a broader summary of the
      evidence, allowing comparison of multiple treatments, and they can be helpful in
      investigating discordant findings from multiple systematic reviews. However,
      there are some specific characteristics concerning methodology in conducting
      overviews. Questions that arise are how to deal with overlapping reviews, how the
      quality of the included reviews should be assessed, how discordant results should
      be dealt with, whether and how additional searches for current primary studies
      should be conducted. Overviews of reviews often lack methodological rigour.
      Methodological standards and reporting guidelines for overviews are needed to
      improve the quality of this new publication type. 

PMID- 24315330
TI  - [The Balance of Care approach for the development of custom-fit health care
      services for people with dementia on the margins of care between home and nursing
      home: experiences with its application in Germany].
AB  - INTRODUCTION: In Germany as in other countries of the European Union (EU), the
      majority of people with dementia are cared for by their informal caregivers at
      home. Across countries, however, there are considerable differences in the time
      to nursing home admission. The European research project RightTimePlaceCare
      intends to establish good practice recommendations for how to sustain the
      preferred living situation as long as possible. The Balance of Care approach was
      used to develop these recommendations, which combines empirical data, cost
      estimates and expert consensus, and thus implemented in a multinational context
      for the first time. METHOD: In eight EU countries a survey was conducted among
      2,014 people with dementia and their informal caregivers in nursing homes
      (n=1,223) or at home (n=791). Selected descriptive characteristics of the study
      participants were used for case type development. The case types were translated
      into 14 case vignettes, which were discussed by five to six expert panels (each
      consisting of three to four participants) per country. The experts (n=161)
      recommended the most suitable living place (at home or in a nursing home) and
      customised care packages for home care situations. RESULTS AND STATE OF AFFAIRS:
      Across all countries, the experts predominantly recommended care at home for four
      of the case types whose reference group of study participants actually lived in a
      nursing home. These case types represent a relevant part of the study population.
      In Germany, the experts judged the case vignettes as realistic but criticised
      that information relevant for proper decision making was missing. Expert group
      discussions always ended in consensus, and care at home was predominately
      recommended. The proposed care packages most often comprised standard care
      services, and hence appeared to be realistic and feasible. The development of
      country-specific recommendations is still ongoing. In order to assess economic
      feasibility, estimated costs of home care packages will be compared with costs of
      nursing home care. Further outcomes like the quality of life will be considered
      for good practice recommendation finding. CONCLUSION: Balance of Care supports
      the development of empirically based expert recommendations. The approach is
      widely applicable but seems to be particularly useful for the development of
      local custom-fit healthcare services. The clinical effectiveness, safety, and
      cost implications of the Balance of Care approach remain to be investigated in
      future studies.

PMID- 24315331
TI  - [Scientability - a concept for the handling of homeopathic remedies by EbM].
AB  - Evidence-based medicine (EbM) has proved to be very useful in healthcare; thanks
      to its methodology the reliability of our knowledge of the benefits and harms of
      interventions can be assessed. This at least applies to interventions which are
      based on a plausible concept for their mechanism of action and which have already
      achieved positive effects in experiments and simple studies. However, for
      interventions whose concepts contradict scientific findings EbM has proved to be
      unsuitable; it has not been able to prevent that they are still regarded as
      effective amongst wide parts of the population and medical experts. Particularly
      homeopathy has managed to even present itself as scientifically justified by
      using EbM. With the aim of highlighting the speculative character of homeopathy
      and other procedures and of preventing EbM from getting damaged, the concept of
      scientability is introduced in this article. This concept only approves of
      clinical studies if the intervention that is to be tested does not contradict
      definite scientific findings. 

PMID- 24315332
TI  - [Preparedness - decisions in the face of uncertainty. Evaluation of nurses'
      response readiness in hospital emergency exercises].
AB  - Events in which the health and life of a large number of people are at stake
      impose particular challenges to all who are involved in healthcare. An effective
      response requires prompt decision-making under time pressure, in a context
      characterised by uncertainty and low routine. The hypothesis is that healthcare
      staffs' preparedness-related competency increases response quality. An evaluation
      tool was developed to assess response-relevant competencies of emergency nurses.
      Competencies relevant to the German healthcare system were systematically defined
      and operationalised into observable items. Multiple phases of qualitative field
      studies were employed to develop a conceptual guide to planning and conducting
      the evaluation. The usability of the evaluation tool was piloted and iteratively
      optimised. The resulting evaluation approach has the potential to substantiate
      education and training in the context of curriculum development. 

PMID- 24315333
TI  - [Development of a decision aid on post mortem organ donation - somewhere between
      evidence uncertainty, fears, and ethical and moral values].
AB  - The recently revised German transplantation law provides that people are to be
      supported to make informed decisions on post-mortem organ donation by
      implementing broad education campaigns. A comprehensive web-based decision aid
      "organ donation after death" was developed, evaluated and optimised utilising
      multiple methodological phases. The decision aid comprises 1) factual information
      in a question-answer format, 2) tools for the individual assessment of this
      information, and 3) narratives addressing attitudes and emotional aspects. The
      website content was compiled by participating experts and potential users of the
      decision aid. Potential users also participated in the usability evaluation.
      Version 1.0 was made publicly available on the Internet in April 2012. Currently,
      version 2.0 of the decision aid is being updated step-by-step, based on the
      results of the evaluation. 

PMID- 24315334
TI  - [Dealing with diagnostic uncertainty in general practice].
AB  - In general, the prevalence of diseases is low in primary care. Therefore, the
      positive predictive value of diagnostic tests is lower than in hospitals where
      patients are highly selected. In addition, the patients present with milder forms
      of disease; and many diseases might hide behind the initial symptom(s). These
      facts lead to diagnostic uncertainty which is somewhat inherent to general
      practice. This narrative review discusses different sources of and reasons for
      uncertainty and strategies to deal with it in the context of the current
      literature. Fear of uncertainty correlates with higher diagnostic activities. The
      attitude towards uncertainty correlates with the choice of medical speciality by
      vocational trainees or medical students. An intolerance of uncertainty, which
      still increases as medicine is making steady progress, might partly explain the
      growing shortage of general practitioners. The bio-psycho-social context appears
      to be important to diagnostic decision-making. The effect of intuition and
      heuristics are investigated by cognitive psychologists. It is still unclear
      whether these aspects are prone to bias or useful, which might depend on the
      context of medical decisions. Good communication is of great importance to share
      uncertainty with the patients in a transparent way and to alleviate shared
      decision-making. Dealing with uncertainty should be seen as an important core
      component of general practice and needs to be investigated in more detail to
      improve the respective medical decisions. 

PMID- 24315335
TI  - [GRADE guidelines: 11. Making an overall rating of confidence in effect estimates
      for a single outcome and for all outcomes].
AB  - GRADE requires guideline developers to make an overall rating of confidence in
      estimates of effect (quality of evidence-high, moderate, low, or very low) for
      each important or critical outcome. GRADE suggests, for each outcome, the initial
      separate consideration of five domains of reasons for rating down the confidence
      in effect estimates, thereby allowing systematic review authors and guideline
      developers to arrive at an outcome-specific rating of confidence. Although this
      rating system represents discrete steps on an ordinal scale, it is helpful to
      view confidence in estimates as a continuum, and the final rating of confidence
      may differ from that suggested by separate consideration of each domain. An
      overall rating of confidence in estimates of effect is only relevant in settings
      when recommendations are being made. In general, it is based on the critical
      outcome that provides the lowest confidence. 

PMID- 24315336
TI  - [GRADE guidelines: 12. Developing Summary of Findings tables - dichotomous
      outcomes].
AB  - Summary of Findings (SoF) tables present, for each of the seven (or fewer) most
      important outcomes, the following: the number of studies and number of
      participants; the confidence in effect estimates (quality of evidence); and the
      best estimates of relative and absolute effects. Potentially challenging choices
      in preparing SoF tables include using direct evidence (which may have very few
      events) or indirect evidence (from a surrogate) as the best evidence for a
      treatment effect. If a surrogate is chosen, it must be labeled as substituting
      for the corresponding patient-important outcome. Another such choice is
      presenting evidence from low-quality randomised trials or high-quality
      observational studies. When in doubt, a reasonable approach is to present both
      sets of evidence; if the two bodies of evidence have similar quality but
      discrepant results, one would rate down further for inconsistency. For binary
      outcomes, relative risks (RRs) are the preferred measure of relative effect and,
      in most instances, are applied to the baseline or control group risks to generate
      absolute risks. Ideally, the baseline risks come from observational studies
      including representative patients and identifying easily measured prognostic
      factors that define groups at differing risk. In the absence of such studies,
      relevant randomised trials provide estimates of baseline risk. When confidence
      intervals (CIs) around the relative effect include no difference, one may simply
      state in the absolute risk column that results fail to show a difference, omit
      the point estimate and report only the CIs, or add a comment emphasizing the
      uncertainty associated with the point estimate. KEY STATEMENTS: Summary of
      Findings (SoF) tables provide succinct; easily digestible presentations of
      confidence in effect estimates (quality of evidence) and magnitude of effects.
      SoF tables should present the seven (or fewer) most important outcomes. These
      outcomes must always be patient-important outcomes and never be surrogates,
      although surrogates can be used to estimate effects on patient-important
      outcomes. SoF tables should present the highest quality evidence. When the
      quality of two bodies of evidence (e.g., randomised trials and observational
      studies) is similar, SoF tables may include summaries from both. SoF tables
      should include both relative and absolute effect measures, and separate estimates
      of absolute effect for identifiable patient groups with substantially different
      baseline or control group risks.

PMID- 24315337
TI  - Simultaneous quantification of mefloquine (+)- and (-)-enantiomers and the
      carboxy metabolite in dried blood spots by liquid chromatography/tandem mass
      spectrometry.
AB  - Mefloquine (MQ), a racemic mixture of (+)-(11S,12R)- and (-)-(11R,12S)-MQ, has
      been used for treatment and prophylaxis of malaria for almost 30 years. MQ is
      metabolized by the cytochrome P450 3A subfamily to 4-carboxymefloquine (CMQ),
      which shows no antimalarial activity in vitro. Highly stereospecific
      pharmacokinetics of MQ have been reported, although with contradictory results.
      This might be due to incorrect assignment of the absolute configuration as shown
      only recently. Gastrointestinal as well as neuropsychiatric adverse events were
      described after prophylaxis and treatment with MQ. Data are indicating that the
      tolerability of the enantiomers may vary considerably. An involvement of the main
      metabolite CMQ in the development of neuropsychiatric adverse events has also
      been supposed. Due to these inconsistent results we established a novel liquid
      chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous
      quantification of MQ enantiomers and the metabolite CMQ to investigate the
      attribution of efficacy and adverse effects to the single enantiomers as well as
      the main metabolite. Separation of the MQ enantiomers was achieved on a quinidine
      based zwitterionic chiral stationary phase column, CHIRALPAK((r)) ZWIX(-)
      (3.0*150mm, 3MUm) in an isocratic run using a pre-mixed eluent consisting of
      methanol/acetonitrile/water (49:49:2 v/v) with 25mM formic acid and 12.5mM
      ammonium formate. We used stable isotope-labelled analogues as internal
      standards. The method was validated according to the FDA guidelines. With a
      linear calibration range from 5 to 2000nM for the MQ enantiomers and from 13 to
      2600nM for CMQ respectively, the method was successfully applied to dried blood
      spot (DBS) samples from patients under prophylactic MQ treatment. The method was
      also applicable for plasma samples. 

PMID- 24315338
TI  - Don't move during ablation of atrial fibrillation!
AB  - BACKGROUND: Restless patient is recalcitrant during ablation of atrial
      fibrillation (AF). We aimed to assess the association between patient movements
      during AF ablation and its outcome. METHODS: We examined the body movement during
      AF ablation in 78 patients with the use of a novel portable respiratory monitor,
      the SD-101, which also has the ability to quantify the frequency of body
      movements. RESULTS: The body movement index, defined as the number of the units
      of time with body movement events divided by the recording time (11.4 +/- 6.5
      events/h), was significantly correlated with the ablation time defined as the
      time from the first point of the ablation to the end of the procedure (1.2 +/-
      0.3h) (r=0.35; p=0.0014) and a total radiofrequency energy applied (56.6 +/- 17.7
      kW) (r=0.36; p=0.0015). A multiple linear regression analysis showed that non
      paroxysmal AF (beta=0.25; p=0.036) and the body movement index (beta=0.36;
      p=0.0019) were independent determinants of the ablation time. The body movement
      index was similar in patients with and without recurrence of AF. CONCLUSIONS:
      Keeping patients motionless may be important to reduce the procedural duration of
      AF ablation.

PMID- 24315339
TI  - Revisiting a classical clinical sign: jugular venous ultrasound.
AB  - BACKGROUND: Increased jugular venous pressure, reflecting the increased right
      atrial pressure, is a classical sign of heart failure (HF) but clinical
      assessment may be difficult. METHODS: In ambulatory patients with HF and control
      subjects, jugular vein diameter (JVD) was measured using a linear high-frequency
      ultrasound probe (10 MHz) at rest, during a Valsalva manoeuvre and during deep
      inspiration. JVD ratio was calculated as diameter during Valsalva to that at
      rest. RESULTS: 211 patients (mean age 70 years; mean left ventricular ejection
      fraction 43%) and 20 controls were included. JVD (median and inter-quartile [IQR]
      range) at rest was 0.17 (0.15-0.20) cm in controls and 0.23 (0.17-0.33) cm in
      patients with HF (p=0.012), JVD ratio was 6.3 (4.3-6.8) in controls and 4.4 (2.7
      5.8) in patients with HF (p=0.001).With increasing quartiles of plasma NT-proBNP,
      JVD at rest rose (0.20 (0.15-0.23) cm, 0.21 (0.16-0.29) cm, 0.25 (0.18-0.35) cm
      and 0.34 (0.20-0.53) cm (P=<0.001), whilst JVD ratio decreased (5.4 (4.2-6.4),
      4.4 (3.5-6.3), 3.9 (2.4-5.4) and 2.8 (1.7-4.7); p=<0.001). JVD ratio correlated
      with log (NT-proBNP) (r=-0.39, p=<0.001), LV filling pressures (E/E', r=-0.33,
      p=<0.001) and left atrial volume (r=-0.21, p=0.002). In a multivariable
      regression model, only trans-tricuspid gradient and TAPSE were independently
      associated with JVD ratio (R(2)=0.27). CONCLUSIONS: Distension of the JV at rest
      relative to the maximum diameter during a Valsalva manoeuvre (JVD ratio)
      identifies patients with heart failure who have higher plasma NT-proBNP levels,
      right ventricular dysfunction and raised pulmonary artery pressure.

PMID- 24315340
TI  - Frequent biomarker analysis in the isolated perfused heart reveals two distinct
      phases of reperfusion injury.
AB  - BACKGROUND: Reperfusion injury and its modulation are incompletely characterized.
      The purpose of the present study was to characterize the dynamics of reperfusion
      injury by portraying the temporal release of lactate dehydrogenase (LDH) during
      ischemia-reperfusion injury in an isolated heart model. METHODS: We studied
      infarct size and LDH release in the following groups: I) Effect of reperfusion
      length was evaluated in 79 rats subjected to 40 minute ischemia and 60, 90, 120
      or 180 minute reperfusion and a) ischemic preconditioning (IPC) or b) No IPC
      (control). II) LDH release kinetics was studied in 6 rats subjected to calcium
      paradox to verify the applicability of LDH as a dynamic marker of cellular
      injury. III) Ischemia-reperfusion injury modification was studied in 36 rats
      subjected to: a) ischemic postconditioning, b) prolonged ischemia, c) Reperfusion
      Injury Salvage Kinase (RISK) pathway inhibition with wortmannin in IPC hearts, d)
      RISK activation with insulin or e) mitochondrial permeability transition pore
      (mPTP) inhibition with cyclosporine A. RESULTS: Infarct size increased from 60 to
      180 minute reperfusion in control hearts. LDH was released in two separate peaks
      from 2 to 20 and 30 to 120 min of reperfusion. IPC attenuated both peaks.
      Postconditioning and agents known to modify reperfusion injury attenuated the
      second peak. CONCLUSIONS: Frequent measurement of myocardial ischemia markers for
      120 min of reperfusion allows identification of two phases of reperfusion injury
      that are affected by cardioprotective stimuli. The second phase contributes
      significantly to final infarct size, which is modifiable and a potential target
      for cardioprotective interventions.

PMID- 24315341
TI  - Indoor temperature below 18 degrees C accounts for 9% population attributable
      risk for high blood pressure in Scotland.

PMID- 24315342
TI  - The impact of exercise intensity on cardiac troponin I release.

PMID- 24315343
TI  - Left ventricular geometry and outcomes in patients with atrial fibrillation: the
      AFFIRM Trial.
AB  - BACKGROUND: Echocardiographically determined left ventricular hypertrophy (LVH)
      is a marker of cardiovascular disease related to prognosis and clinical outcomes.
      We sought to determine if LVH is a measure of outcomes in atrial fibrillation
      (AF) patients. METHODS: We performed a post-hoc analysis of patients with
      echocardiographic data enrolled in the Atrial Fibrillation Follow-up
      Investigation of Rhythm Management (AFFIRM) Trial. Patients were stratified based
      on gender-adjusted echocardiography derived interventricular septal (IVS)
      thickness, relative wall thickness (RWT), gender-adjusted LV mass, and type of LV
      remodeling (normal LV geometry, concentric hypertrophy, eccentric hypertrophy,
      and concentric remodeling). RESULTS: Of 4060 patients in AFFIRM,
      echocardiographic data were available in 2433 patients (60%). Multivariate
      analysis revealed that LVH defined as moderately or severely abnormal IVS
      thickness was an independent predictor of both all cause mortality (HR 1.46,
      95%CI 1.14-1.86, p=0.003) and stroke (HR 1.89, 95%CI 1.17-3.08, p=0.01). This
      association was confirmed when IVS thickness was assessed as continuous or
      categorical variable. Concentric LV hypertrophy was associated with the highest
      rates of all cause mortality (HR 1.53; 95%CI 1.11-2.12; p=0.009). CONCLUSION: An
      easily obtained echocardiographic index of LVH (IVS thickness) may enhance risk
      stratification of patients with AF, and raise the possibility that LVH regression
      should be a therapeutic target in this population.

PMID- 24315344
TI  - Titin mutation in familial restrictive cardiomyopathy.
AB  - BACKGROUND: Familial restrictive cardiomyopathy (RCM) caused by a single gene
      mutation is the least common of the inherited cardiomyopathies. Only a few RCM
      causing mutations have been described. Most mutations causing RCM are located in
      sarcomere protein genes which also cause hypertrophic cardiomyopathy (HCM). Other
      genes associated with RCM include the desmin and familial amyloidosis genes. In
      the present study we describe familial RCM with severe heart failure triggered by
      a de novo mutation in TTN, encoding the huge muscle filament protein titin.
      METHODS AND RESULTS: Family members underwent physical examination, ECG and
      Doppler echocardiogram studies. The family comprised 6 affected individuals aged
      12-35 years. Linkage to candidate loci was performed, followed by gene
      sequencing. Candidate loci/gene analysis excluded 18 candidate genes but showed
      segregation with a common haplotype surrounding the TTN locus. Sequence analysis
      identified a de novo mutation within exon 266 of the TTN gene, resulting in the
      replacement of tyrosine by cysteine. p.Y7621C affects a highly conserved region
      in the protein within a fibronectin-3 domain, belonging to the A/I junction
      region of titin. No other disease-causing mutation was identified in
      cardiomyopathy genes by whole exome sequencing. CONCLUSIONS: Our study shows, for
      the first time, that mutations in TTN can cause restrictive cardiomyopathy. The
      giant filament titin is considered to be a determinant of a resting tension of
      the sarcomere and this report provides genetic evidence of its crucial role in
      diastolic function.

PMID- 24315346
TI  - Development and evaluation of an educational website for adults with cystic
      fibrosis.
AB  - BACKGROUND: The high prevalence of internet use among adults with cystic fibrosis
      (CF) provides an opportunity for healthcare professionals to use the internet as
      a tool for patient education. The Toronto Adult Cystic Fibrosis website was
      developed, implemented, and evaluated (www.torontoadultcf.com). METHODS: The
      website structure and content were developed following a needs assessment
      questionnaire. The website was evaluated with a satisfaction survey and through
      examination of compliance to American Medical Association (AMA)'s guidelines for
      health information sites. RESULTS: Users showed a high prevalence of internet
      usage (98.7%), described a need for more information about CF and provided
      content suggestions. A satisfaction survey revealed that CF patients compose the
      highest proportion of site users (57.5%), and users perceive the site as useful,
      with a mean score of 4.3 on a five-point satisfaction scale. Key areas for
      improvement have been identified. Website compliance with AMA guidelines was
      excellent at 80%. CONCLUSIONS: The Toronto Adult CF website provides needed
      information for our patients. Future directions include ongoing improvement of
      the website as a patient resource and assessment of the ability of the website to
      improve patient knowledge and outcomes.

PMID- 24315347
TI  - Paradoxical embolism associated with Ebstein's anomaly in an adult: case report.
AB  - Ebstein's anomaly (EA) is a rare congenital malformation of the tricuspid valve,
      often associated with other cardiac malformations, especially atrial septal
      defect, which is present in 80-90% of patients and predisposes to paradoxical
      embolization. We describe the case of a 47-year-old male, a drug abuser, with a
      known but not investigated cardiac murmur. He presented to the emergency
      department with worsening exertional dyspnea and fatigue associated with recent
      recurrent transient ischemic attacks. On brain computed tomography there were
      multiple non-recent ischemic infarctions. Transthoracic echocardiography showed
      EA with severely dilated right cardiac chambers, right systolic dysfunction and
      severe tricuspid regurgitation. Contrast and transesophageal echocardiography
      revealed a patent foramen ovale with right-to-left shunt. After exclusion of
      other potential causes of the neurologic events, they were assumed to be the
      consequence of paradoxical embolism. 

PMID- 24315348
TI  - Structurally characterized arabinogalactan from Anoectochilus formosanus as an
      immuno-modulator against CT26 colon cancer in BALB/c mice.
AB  - In this study, the innate immuno-modulatory effects and anti-cancer action of
      arabinogalactan (AG), a derivative of a well-known orchid, Anoectochilus
      formosanus, were investigated. The innate immuno-modulatory effects of AG were
      determined in vitro using RAW 264.7 cells for microarray analysis, and in vivo
      using BALB/c mice administrated with AG at 5 and 15 mg/kg intra-peritoneally for
      3 weeks. The anti-cancer activity of AG was evaluated by CT26 colon cancer
      bearing BALB/c mice. The microarray analysis was performed to evaluate the innate
      immunity and demonstrated that AG significantly induced the expression of
      cytokines, chemokines, and co-stimulatory receptors, such as IL-1alpha, CXCL2,
      and CD69. An intraperitoneal injection of AG in mice increased the spleen weight,
      but not the body weight. The treatment of mitogen, LPS significantly stimulated
      splenocyte proliferation in AG treated groups. The AG treatment also promoted
      splenocyte cytotoxicity against YAC-1 cells and increased the percentage of
      CD3(+)CD8(+) cytotoxic T cells in innate immunity test. Our experiments revealed
      that AG significantly decreased both tumour size and tumour weight. Besides, AG
      increased the percentage of DC, CD3(+)CD8(+) T cells, CD49b(+)CD3(-) NK cells
      among splenocytes, and cytotoxicity activity in tumour-bearing mice. In addition,
      the immunohistochemistry of the tumour demonstrated that the AG treatments
      increased the tumour-filtrating NK and cytotoxic T-cell. These results
      demonstrated that AG, a polysaccharide derived from a plant source, has potent
      innate immuno-modulatory and anti-cancer activity. AG may therefore be used for
      cancer immunotherapy.

PMID- 24315345
TI  - Association between an interleukin 1 receptor, type I promoter polymorphism and
      self-reported attentional function in women with breast cancer.
AB  - Subgroups of patients with breast cancer may be at greater risk for cytokine
      induced changes in cognitive function after diagnosis and during treatment. The
      purposes of this study were to identify subgroups of patients with distinct
      trajectories of attentional function and evaluate for phenotypic and genotypic
      (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self
      reported attentional function was evaluated in 397 patients with breast cancer
      using the Attentional Function Index before surgery and for six months after
      surgery (i.e., seven time points). Using growth mixture modeling, three
      attentional function latent classes were identified: High (41.6%), Moderate
      (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were
      significantly younger than those in the High class, with more comorbidities and
      lower functional status than the other two classes. No differences were found
      among the classes in years of education, race/ethnicity, or other clinical
      characteristics. DNA was recovered from 302 patients' samples. Eighty-two single
      nucleotide polymorphisms among 15 candidate genes were included in the genetic
      association analyses. After controlling for age, comorbidities, functional
      status, and population stratification due to race/ethnicity, IL1R1 rs949963
      remained a significant genotypic predictor of class membership in the
      multivariable model. Carrying the rare "A" allele (i.e., GA+AA) was associated
      with a twofold increase in the odds of belonging to a lower attentional function
      class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of
      subgroups of women with breast cancer who report distinct trajectories of
      attentional function and of a genetic association between subgroup membership and
      an IL1R1 promoter polymorphism. 

PMID- 24315349
TI  - Effects of safranal, a constituent of saffron, and vitamin E on nerve functions
      and histopathology following crush injury of sciatic nerve in rats.
AB  - Safranal is one of the major components of saffron and has many biological
      effects such as antioxidant property. The present study investigated the effects
      of safranal on sciatic nerve function after induction of crush injury. We also
      used of vitamin E as a reference potent antioxidant agent. In anesthetized rats,
      right sciatic nerve was crushed using a small haemostatic forceps. Functional
      recovery was assessed using sciatic functional index (SFI). Acetone spray and von
      Frey filament tests were used for neuropathic pain assay. Histopathological
      changes including severities of Wallerian degeneration of sciatic nerve and
      gastrocnemius muscle atrophy were investigated by light microscopy. Blood levels
      of malodialdehyde (MDA) were also measured. The SFI values were accelerated, cold
      and mechanical allodynia were suppressed, the severities of Wallerian
      degeneration and muscular atrophy were improved, and the increased MDA level was
      reversed with 10 consecutive days intraperitoneal injections of 0.2 and 0.8 mg/kg
      of safranal and 100 mg/kg of vitamin E. It is concluded that safranal and vitamin
      E produced same improving effects on crushed-injured sciatic nerve functions.
      Inhibition of oxidative stress pathway may be involved in improving effects of
      safranal and vitamin E on functions and histopathology of an injured peripheral
      nerve.

PMID- 24315350
TI  - An unusual case of cardiac glycoside toxicity.

PMID- 24315351
TI  - Atrial natriuretic peptide as a predictor of atrial fibrillation in a male
      population study. The Study of Men Born in 1913 and 1923.
AB  - BACKGROUND: Atrial fibrillation is one of the most common arrhythmias in clinical
      practice and it is often diagnosed after a complication occurs. The study aimed
      to evaluate the predictive value of atrial natriuretic peptide (ANP) for atrial
      fibrillation in a male population-based study. METHODS AND RESULTS: This study is
      a part of the "Study of Men Born in 1913 and 1923", a longitudinal prospective
      cohort study of men, living in the city of Gothenburg in Sweden. A population
      based sample of 528 men was investigated in 1988 when they were aged 65 years
      (n=134) and 75 years (n=394), and they were followed up for 16 years. Blood
      samples were collected from all 528 men at baseline and plasma ANP levels were
      analyzed by radioimmunoassay. Hazard ratios were estimated by competing-risk
      regression analysis. One hundred five participants were excluded because of a
      prior diagnosis of atrial fibrillation, congestive heart failure, severe
      hypertension, or severe chronic renal insufficiency. Of the remaining 423
      participants, 90 men were diagnosed with atrial fibrillation over the 16-year
      follow-up. In multivariable analysis, men in the two highest quartiles of ANP
      levels had a significantly higher risk for atrial fibrillation compared with men
      in the lowest ANP quartile. The adjusted ratio was 3.14 (95% CI 1.59-6.20) for
      the third ANP quartile and 3.36 (95% CI 1.72-6.54) for the highest quartile of
      ANP level. CONCLUSIONS: In this population-based longitudinal study, we found
      that elevated ANP levels at baseline predicted atrial fibrillation during a
      follow-up time of 16 years.

PMID- 24315352
TI  - Links between allergy and cardiovascular or hemostatic system.
AB  - In addition to a well-known immunologic background of atherosclerosis and
      influences of inflammation on arterial and venous thrombosis, there is growing
      evidence for the presence of links between allergy and vascular or thrombotic
      disorders. In this interpretative review, five pretty well-documented areas of
      such overlap are described and discussed, including: (1) links between
      atherosclerosis and immunoglobulin E or atopy, (2) mutual effects of blood lipids
      and allergy, (3) influence of atopy and related disorders on venous
      thromboembolism, (4) the role of platelets in allergic diseases, and (5) the
      functions of protein C system in atopic disorders. 

PMID- 24315353
TI  - Surgical management of non-epithelial ovarian malignancies: advantages and
      limitations of laparoscopy.
AB  - OBJECTIVE: To compare open and laparoscopic surgery in the management of non
      epithelial ovarian malignancies. STUDY DESIGN: Retrospective study from
      University Hospital of Clermont-Ferrand, France, of 20 patients undergoing
      surgery for non-epithelial ovarian malignancies. We compared the outcome of 13
      open surgeries and 7 laparoscopic surgeries. The main outcome measures were stage
      and size of the tumor, surgical procedure, hospital stay, adjuvant treatment,
      follow-up and fertility. RESULTS: The mean age of the patients and the type of
      tumor at the time of diagnosis were similar in the two groups but the tumor size
      was significantly larger in the laparotomy group (14.0cm vs. 6.7cm; p<0.05).
      Treatment was conservative in 85.6% vs. 61.5% in the laparoscopy and laparotomy
      groups respectively. Tumor stages were not statistically different in the two
      groups. The hospital stay was shorter in the laparoscopy group (3.1 days vs. 6.9
      days p=0.03) and there were no differences in terms of complications, surgical
      procedures, number of lymph nodes removed and adjuvant treatment. CONCLUSIONS:
      Laparoscopy respecting the usual oncologic principles appears to be a good
      alternative to laparotomy for the initial management of non-epithelial ovarian
      malignancies. The limiting factors of this technique remain the tumor size, the
      tumor stages and the surgeon's experience.

PMID- 24315354
TI  - Retroperitoneal and retrograde total laparoscopic hysterectomy as a standard
      treatment in a community hospital.
AB  - OBJECTIVE: To report our experience with a modified procedure for total
      laparoscopic hysterectomy based on a retrograde and retroperitoneal technique.
      This surgical approach is analyzed on a consecutive series of patients in a
      community hospital and theoretical educational advantages are proposed. STUDY
      DESIGN: All patients undergoing hysterectomy from January 2012 to April 2013 were
      included in the study. A detailed description of the technique is given. As main
      outcome measures we evaluated: the number and rate of patients excluded from
      laparoscopic approach, the rate of late complications need readmission, the rate
      of transfusions, the rate of conversion to laparotomy and the number of minor
      complications. The main concern of the study was ureteral complications. RESULTS:
      Overall 174 patients underwent hysterectomy in our unit. The rate of patients
      submitted to laparoscopic hysterectomy was 97.5%. The number of complications
      needing re-admission was three (2%). The rate of conversion was 2.7%. In the
      study period, two (1.2%) ureteral complications were observed (late fistulae).
      There were four bladder lesions but the patients were released on the same day as
      the patients with no lesion. CONCLUSIONS: Opening the retroperitoneum allows
      rapid control of the main uterine vessels by coagulation, and constant checks on
      the ureter. Difficult benign situations can be managed. Even in a non-referral
      center about 94% of hysterectomies can be performed by laparoscopic surgery. This
      approach is helpful and may be reproducible in gynecological procedures.

PMID- 24315355
TI  - Electrospun modified silica-polyamide nanocomposite as a novel fiber coating.
AB  - In the present work, a new solid phase microextraction (SPME) fiber coating based
      on modified silica-polyamide (PA) nanocomposite was electrospun on a stainless
      steel wire. Four modified silica-PA nanocomposites together with PA were
      fabricated by dispersing several typical modified silica nanoparticles in PA
      polymer solution prior to electrospinning. The surface characteristic of PA
      nanofibers and modified silica-PA nanocomposites was investigated using scanning
      electron microscopy (SEM). The homogeneity and the porous surface structure of
      the modified silica-PA nanocomposites were confirmed by SEM, showing nanofibers
      diameters lower than 170 nm. The applicability of the new fiber coating was
      examined by headspace SPME of some selected chlorobenzenes (CBs), as model
      compounds, from aqueous samples. Subsequently, the extracted analytes were
      transferred into a gas chromatography (GC) by thermal desorption. Influencing
      parameters on the morphology of nanocomposites such as type of modified silica
      nanoparticles and the weight ratio of components were optimized. In addition,
      effects of different parameters influencing the extraction efficiency including
      extraction temperature, extraction time, ionic strength, desorption temperature,
      and desorption time were investigated and optimized. Eventually, the developed
      method was validated by gas chromatography-mass spectrometry (GC-MS). At the
      optimum conditions, the relative standard deviation values for a double distilled
      water spiked with the selected CBs at 100 ng L(-1) were 4-12% (n=3) and the limit
      of detection for the studied compounds was between 5 and 30 ng L(-1). The
      calibration curves of analytes were investigated in the range of 50-1000 ng L(-1)
      and correlation coefficients (R(2)) between 0.9897 and 0.9992 were obtained.

PMID- 24315356
TI  - Enantioseparation and selective detection of D-amino acids by ultra-high
      performance liquid chromatography/mass spectrometry in analysis of complex
      biological samples.
AB  - The growing scientific attention in the biological function of D-amino acids
      leads to an increasing analytical interest for enantiomeric amino acid
      separation, which is still very challenging due to the lack of sufficiently
      sensitive, high-throughput analytical methods that can cope with often occurring
      matrix interferences and very low D-amino acid concentrations. Here,
      enantioseparation can benefit from improved resolution and chromatographic speed
      offered by modern UHPLC techniques and the precision of MS detection. We
      developed a RP-UHPLC-QqToF-MS method using pre-column OPA/IBLC derivatization for
      very precise discrimination of amino acids enantiomers. The method shows a superb
      sensitivity with limits of detection in the range of several pmol/l. It has
      neither shown matrix inferences in the tested very complex biological matrices
      (serum, plasma, urine and gut) nor stability or racemization problems. 

PMID- 24315357
TI  - Adsorption behavior of proteins on temperature-responsive resins.
AB  - The adsorption behavior of proteins on thermo-responsible resins based on poly(N
      isopropylacrylamide) and its copolymer containing an anionic co-monomer has been
      investigated. The influence of the polymer composition, i.e., the content of the
      co-monomer and crosslinker on the thermo-sensitivity of the protein adsorption
      has been quantified. The properties of ungrafted polymer as well grafted onto the
      agarose matrix have been analyzed and compared. Batch and dynamic (column)
      experiments have been performed to measure the adsorption equilibrium of proteins
      and to quantify the phase transition process. As model proteins lysozyme,
      lactoferrin, alpha-chymotrypsinogen A and ovalbumin have been used. The
      adsorption process was found to be governed by ionic interactions between the
      negatively charged surface of resin and the protein, which enabled separation of
      proteins differing in electrostatic charge. The interactions enhanced with
      increase of temperature. Decrease of temperature facilitated desorption of
      proteins and reduced the salt usage in the desorption buffer. Grafted polymers
      exhibited markedly higher mechanical stability and, however, weaker temperature
      response compared to the ungrafted ones. 

PMID- 24315358
TI  - Non-aqueous capillary electrophoresis for the analysis of acidic compounds using
      negative electrospray ionization mass spectrometry.
AB  - Non-aqueous capillary electrophoresis (NACE) is an attractive CE mode, in which
      water solvent of the background electrolyte (BGE) is replaced by organic solvent
      or by a mixture of organic solvents. This substitution alters several parameters,
      such as the pKa, permittivity, viscosity, zeta potential, and conductivity,
      resulting in a modification of CE separation performance (i.e., selectivity
      and/or efficiency). In addition, the use of NACE is particularly well adapted to
      ESI-MS due to the high volatility of solvents and the low currents that are
      generated. Organic solvents reduce the number of side electrochemical reactions
      at the ESI tip, thereby allowing the stabilization of the ESI current and a
      decrease in background noise. All these features make NACE an interesting
      alternative to the aqueous capillary zone electrophoresis (CZE) mode, especially
      in combination with mass spectrometry (MS) detection. The aim of this work was to
      evaluate the use of NACE coupled to negative ESI-MS for the analysis of acidic
      compounds with two available CE-MS interfaces (sheath liquid and sheathless).
      First, NACE was compared to aqueous CZE for the analysis of several
      pharmaceutical acidic compounds (non-steroidal anti-inflammatory drugs, NSAIDs).
      Then, the separation performance and the sensitivity achieved by both interfaces
      were evaluated, as were the impact of the BGE and the sample composition.
      Finally, analyses of glucuronides in urine samples subjected to a minimal sample
      pre-treatment ("dilute-and-shoot") were performed by NACE-ESI-MS, and the matrix
      effect was evaluated. A 20- to 100-fold improvement in sensitivity was achieved
      using the NACE mode in combination with the sheathless interface and no matrix
      effect was observed regardless of the interfaces. 

PMID- 24315360
TI  - The on-going quest for treatment precision and conformality in radiotherapy.

PMID- 24315359
TI  - A generative probability model of joint label fusion for multi-atlas based brain
      segmentation.
AB  - Automated labeling of anatomical structures in medical images is very important
      in many neuroscience studies. Recently, patch-based labeling has been widely
      investigated to alleviate the possible mis-alignment when registering atlases to
      the target image. However, the weights used for label fusion from the registered
      atlases are generally computed independently and thus lack the capability of
      preventing the ambiguous atlas patches from contributing to the label fusion.
      More critically, these weights are often calculated based only on the simple
      patch similarity, thus not necessarily providing optimal solution for label
      fusion. To address these limitations, we propose a generative probability model
      to describe the procedure of label fusion in a multi-atlas scenario, for the goal
      of labeling each point in the target image by the best representative atlas
      patches that also have the largest labeling unanimity in labeling the underlying
      point correctly. Specifically, sparsity constraint is imposed upon label fusion
      weights, in order to select a small number of atlas patches that best represent
      the underlying target patch, thus reducing the risks of including the misleading
      atlas patches. The labeling unanimity among atlas patches is achieved by
      exploring their dependencies, where we model these dependencies as the joint
      probability of each pair of atlas patches in correctly predicting the labels, by
      analyzing the correlation of their morphological error patterns and also the
      labeling consensus among atlases. The patch dependencies will be further
      recursively updated based on the latest labeling results to correct the possible
      labeling errors, which falls to the Expectation Maximization (EM) framework. To
      demonstrate the labeling performance, we have comprehensively evaluated our patch
      based labeling method on the whole brain parcellation and hippocampus
      segmentation. Promising labeling results have been achieved with comparison to
      the conventional patch-based labeling method, indicating the potential
      application of the proposed method in the future clinical studies. 

PMID- 24315361
TI  - Treatment planning studies in radiotherapy.

PMID- 24315362
TI  - Developing a burn injury severity score (BISS): adding age and total body surface
      area burned to the injury severity score (ISS) improves mortality concordance.
AB  - BACKGROUND: There is limited research validating the injury severity score (ISS)
      in burns. We examined the concordance of ISS with burn mortality. We hypothesized
      that combining age and total body surface area (TBSA) burned to the ISS gives a
      more accurate mortality risk estimate. METHODS: Data from the Royal Perth
      Hospital Trauma Registry and the Royal Perth Hospital Burns Minimum Data Set were
      linked. Area under the receiver operating characteristic curve (AUC) measured
      concordance of ISS with mortality. Using logistic regression models with death as
      the dependent variable we developed a burn-specific injury severity score (BISS).
      RESULTS: There were 1344 burns with 24 (1.8%) deaths, median TBSA 5% (IQR 2-10),
      and median age 36 years (IQR 23-50). The results show ISS is a good predictor of
      death for burns when ISS<=15 (OR 1.29, p=0.02), but not for ISS>15 (ISS 16-24: OR
      1.09, p=0.81; ISS 25-49: OR 0.81, p=0.19). Comparing the AUCs adjusted for age,
      gender and cause, ISS of 84% (95% CI 82-85%) and BISS of 95% (95% CI 92-98%),
      demonstrated superior performance of BISS as a mortality predictor for burns.
      CONCLUSION: ISS is a poor predictor of death in severe burns. The BISS combines
      ISS with age and TBSA and performs significantly better than the ISS.

PMID- 24315363
TI  - Results of primary percutaneous coronary intervention in patients >=75 years
      treated by the transradial approach.
AB  - Previous trials in elderly patients with ST-elevation myocardial infarction
      (STEMI) have not shown a definitive benefit of primary percutaneous coronary
      intervention (PPCI) by transfemoral approach over thrombolysis. The transradial
      approach (TRA) is associated with a significant decrease in mortality, MACE
      (Major Adverse Cardiac Event), and serious access site complications compared
      with the transfemoral approach. We have evaluated clinical outcomes in a cohort
      of real-life unselected >=75-year-old patients with STEMI treated by TRA-PPCI.
      This is a single-center prospective, observational registry of consecutive
      patients with STEMI who underwent PPCI between February 2007 and February 2013.
      MACE was defined as death, reinfarction, or stroke. A total of 307 patients were
      treated by PPCI, 293 (95.1%) with TRA-PPCI (mean age 80 +/- 2 years, 42% women).
      Patients had high co-morbidity levels (cardiogenic shock on admission 8.5%,
      previous myocardial infarction 11.6%, diabetes 30.4%, previous renal failure
      25.6%, previous PCI 9.6%, and peripheral arterial disease 14.3%); IIbIIIa
      inhibitors were used in 45.1% of patients. Severe bleeding and need for
      transfusion were recorded for 6.5% and 9.9% of patients, respectively. In
      hospital mortality, 1-year mortality, and 1-year MACE were 11.9%, 17.4%, and
      22.2%, respectively. Excluding 25 patients with cardiogenic shock on admission,
      the in-hospital mortality, 1-year mortality, and 1-year MACE were 7.8%, 13.1%,
      and 17.9%, respectively. In conclusion, TRA-PPCI was feasible in the vast
      majority of elderly patients with STEMI. In-hospital mortality, 1-year mortality,
      and 1-year MACE were lower than reported for transfemoral access, suggesting a
      benefit of the TRA in these patients.

PMID- 24315364
TI  - Adipose tissue macrophages: Amicus adipem?
AB  - Chronic overnutrition drives complex adaptations within both professional
      metabolic and bystander tissues that, despite intense investigation, are still
      poorly understood. Xu et al. (2013) now describe the unexpected ability of
      adipose tissue macrophages to buffer lipids released from obese adipocytes in a
      manner independent of inflammatory macrophage activation. 

PMID- 24315365
TI  - Was it something I ate?
AB  - Aversive visceral stimuli, such as those associated with sickness, suppress
      appetite. Yet an understanding of the neural mechanisms underlying illness
      related anorexia has remained elusive. Carter et al. (2013) now identify a
      specific hindbrain -> amygdala circuit that contributes to illness-induced loss
      of appetite.

PMID- 24315366
TI  - Proteostasis impairment: at the intersection between Alzheimer's disease and
      diabetes.
AB  - Altered insulin signaling and neuroinflammation are emerging features of
      Alzheimer's disease. Lourenco et al. (2013) identify a pathogenic mechanism that
      is shared between Alzheimer's disease and diabetes and contributes to memory loss
      through a common molecular event: the control of protein synthesis by PKR and the
      downstream phosphorylation of eIF2alpha.

PMID- 24315367
TI  - Does reduced creatine synthesis protect against statin myopathy?
AB  - Statins, widely used to lower cholesterol levels, cause myopathy in some
      patients. Mangravite et al. (2013) show that a single nucleotide polymorphism
      decreasing expression of glycine amidinotransferase (GATM), the enzyme regulating
      creatine biosynthesis, is associated with reduced statin myopathy. Whether
      reduced creatine production protects against statin myopathy remains to be
      determined. 

PMID- 24315368
TI  - Obesity activates a program of lysosomal-dependent lipid metabolism in adipose
      tissue macrophages independently of classic activation.
AB  - Obesity activates a complex systemic immune response that includes the
      recruitment of macrophages and other immune cells to key metabolic tissues.
      Current models postulate that obesity and excess lipids classically activate
      macrophages, polarizing them toward an M1 (inflammatory) state. Little is known
      about noninflammatory functions of adipose tissue macrophages (ATMs). Here, we
      show that the expansion of adipose tissue (AT) across models of obesity induces a
      program of lysosome biogenesis in ATMs and is associated with lipid catabolism
      but not a classic inflammatory phenotype. This program is induced by factors
      produced by AT and is tightly coupled to lipid accumulation by ATMs. Inhibition
      of ATM lysosome function impairs lipid metabolism and increases lipid content in
      ATMs and reduces whole AT lipolysis. These data argue that ATMs contribute
      quantitatively to the development of obesity-induced inflammation but also serve
      an important role in lipid trafficking independent of their inflammatory
      phenotype. 

PMID- 24315369
TI  - TNF-alpha mediates PKR-dependent memory impairment and brain IRS-1 inhibition
      induced by Alzheimer's beta-amyloid oligomers in mice and monkeys.
AB  - Alzheimer's disease (AD) and type 2 diabetes appear to share similar pathogenic
      mechanisms. dsRNA-dependent protein kinase (PKR) underlies peripheral insulin
      resistance in metabolic disorders. PKR phosphorylates eukaryotic translation
      initiation factor 2alpha (eIF2alpha-P), and AD brains exhibit elevated phospho
      PKR and eIF2alpha-P levels. Whether and how PKR and eIF2alpha-P participate in
      defective brain insulin signaling and cognitive impairment in AD are unknown. We
      report that beta-amyloid oligomers, AD-associated toxins, activate PKR in a tumor
      necrosis factor alpha (TNF-alpha)-dependent manner, resulting in eIF2alpha-P,
      neuronal insulin receptor substrate (IRS-1) inhibition, synapse loss, and memory
      impairment. Brain phospho-PKR and eIF2alpha-P were elevated in AD animal models,
      including monkeys given intracerebroventricular oligomer infusions. Oligomers
      failed to trigger eIF2alpha-P and cognitive impairment in PKR(-/-) and TNFR1(-/-)
      mice. Bolstering insulin signaling rescued phospho-PKR and eIF2alpha-P. Results
      reveal pathogenic mechanisms shared by AD and diabetes and establish that
      proinflammatory signaling mediates oligomer-induced IRS-1 inhibition and PKR
      dependent synapse and memory loss.

PMID- 24315370
TI  - Inflammation-induced alteration of astrocyte mitochondrial dynamics requires
      autophagy for mitochondrial network maintenance.
AB  - Accumulating evidence suggests that changes in the metabolic signature of
      astrocytes underlie their response to neuroinflammation, but how proinflammatory
      stimuli induce these changes is poorly understood. By monitoring astrocytes
      following acute cortical injury, we identified a differential and region-specific
      remodeling of their mitochondrial network: while astrocytes within the penumbra
      of the lesion undergo mitochondrial elongation, those located in the core-the
      area invaded by proinflammatory cells-experience transient mitochondrial
      fragmentation. In brain slices, proinflammatory stimuli reproduced localized
      changes in mitochondrial dynamics, favoring fission over fusion. This effect was
      triggered by Drp1 phosphorylation and ultimately resulted in reduced respiratory
      capacity. Furthermore, maintenance of the mitochondrial architecture critically
      depended on the induction of autophagy. Deletion of Atg7, required for
      autophagosome formation, prevented the reestablishment of tubular mitochondria,
      leading to marked reactive oxygen species accumulation and cell death. Thus, our
      data reveal autophagy to be essential for regenerating astrocyte mitochondrial
      networks during inflammation. 

PMID- 24315371
TI  - Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in
      body weight regulation.
AB  - The melanocortin receptor 4 (MC4R) is a well-established mediator of body weight
      homeostasis. However, the neurotransmitter(s) that mediate MC4R function remain
      largely unknown; as a result, little is known about the second-order neurons of
      the MC4R neural pathway. Single-minded 1 (Sim1)-expressing brain regions, which
      include the paraventricular nucleus of hypothalamus (PVH), represent key brain
      sites that mediate melanocortin action. We conditionally restored MC4R expression
      in Sim1 neurons in the background of Mc4r-null mice. The restoration dramatically
      reduced obesity in Mc4r-null mice. The anti-obesity effect was completely
      reversed by selective disruption of glutamate release from those same Sim1
      neurons. The reversal was caused by lower energy expenditure and hyperphagia.
      Corroboratively, selective disruption of glutamate release from adult PVH neurons
      led to rapid obesity development via reduced energy expenditure and hyperphagia.
      Thus, this study establishes glutamate as the primary neurotransmitter that
      mediates MC4Rs on Sim1 neurons in body weight regulation.

PMID- 24315372
TI  - Role of KATP channels in glucose-regulated glucagon secretion and impaired
      counterregulation in type 2 diabetes.
AB  - Glucagon, secreted by pancreatic islet alpha cells, is the principal
      hyperglycemic hormone. In diabetes, glucagon secretion is not suppressed at high
      glucose, exacerbating the consequences of insufficient insulin secretion, and is
      inadequate at low glucose, potentially leading to fatal hypoglycemia. The causal
      mechanisms remain unknown. Here we show that alpha cell KATP-channel activity is
      very low under hypoglycemic conditions and that hyperglycemia, via elevated
      intracellular ATP/ADP, leads to complete inhibition. This produces membrane
      depolarization and voltage-dependent inactivation of the Na(+) channels involved
      in action potential firing that, via reduced action potential height and Ca(2+)
      entry, suppresses glucagon secretion. Maneuvers that increase KATP channel
      activity, such as metabolic inhibition, mimic the glucagon secretory defects
      associated with diabetes. Low concentrations of the KATP channel blocker
      tolbutamide partially restore glucose-regulated glucagon secretion in islets from
      type 2 diabetic organ donors. These data suggest that impaired metabolic control
      of the KATP channels underlies the defective glucose regulation of glucagon
      secretion in type 2 diabetes.

PMID- 24315373
TI  - The histone H3 methyltransferase G9A epigenetically activates the serine-glycine
      synthesis pathway to sustain cancer cell survival and proliferation.
AB  - Increased activation of the serine-glycine biosynthetic pathway is an integral
      part of cancer metabolism that drives macromolecule synthesis needed for cell
      proliferation. Whether this pathway is under epigenetic control is unknown. Here
      we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for
      maintaining the pathway enzyme genes in an active state marked by H3K9
      monomethylation and for the transcriptional activation of this pathway in
      response to serine deprivation. G9A inactivation depletes serine and its
      downstream metabolites, triggering cell death with autophagy in cancer cell lines
      of different tissue origins. Higher G9A expression, which is observed in various
      cancers and is associated with greater mortality in cancer patients, increases
      serine production and enhances the proliferation and tumorigenicity of cancer
      cells. These findings identify a G9A-dependent epigenetic program in the control
      of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic
      strategy for cancer.

PMID- 24315374
TI  - Stress-regulated translational attenuation adapts mitochondrial protein import
      through Tim17A degradation.
AB  - Stress-regulated signaling pathways protect mitochondrial proteostasis and
      function from pathologic insults. Despite the importance of stress-regulated
      signaling pathways in mitochondrial proteome maintenance, the molecular
      mechanisms by which these pathways maintain mitochondrial proteostasis remain
      largely unknown. We identify Tim17A as a stress-regulated subunit of the
      translocase of the inner membrane 23 (TIM23) mitochondrial protein import
      complex. We show that Tim17A protein levels are decreased downstream of stress
      regulated translational attenuation induced by eukaryotic initiation factor
      2alpha (eIF2alpha) phosphorylation through a mechanism dependent on the
      mitochondrial protease YME1L. Furthermore, we demonstrate that decreasing Tim17A
      attenuates TIM23-dependent protein import, promotes the induction of
      mitochondrial unfolded protein response (UPR)-associated proteostasis genes, and
      confers stress resistance in C. elegans and mammalian cells. Thus, our results
      indicate that Tim17A degradation is a stress-responsive mechanism by which cells
      adapt mitochondrial protein import efficiency and promote mitochondrial
      proteostasis in response to the numerous pathologic insults that induce stress
      regulated translation attenuation.

PMID- 24315376
TI  - The construction of visual-spatial situation models in children's reading and
      their relation to reading comprehension.
AB  - Readers construct mental models of situations described by text to comprehend
      what they read, updating these situation models based on explicitly described and
      inferred information about causal, temporal, and spatial relations. Fluent adult
      readers update their situation models while reading narrative text based in part
      on spatial location information that is consistent with the perspective of the
      protagonist. The current study investigated whether children update spatial
      situation models in a similar way, whether there are age-related changes in
      children's formation of spatial situation models during reading, and whether
      measures of the ability to construct and update spatial situation models are
      predictive of reading comprehension. Typically developing children from 9 to 16
      years of age (N=81) were familiarized with a physical model of a marketplace.
      Then the model was covered, and children read stories that described the movement
      of a protagonist through the marketplace and were administered items requiring
      memory for both explicitly stated and inferred information about the character's
      movements. Accuracy of responses and response times were evaluated. Results
      indicated that (a) location and object information during reading appeared to be
      activated and updated not simply from explicit text-based information but from a
      mental model of the real-world situation described by the text; (b) this pattern
      showed no age-related differences; and (c) the ability to update the situation
      model of the text based on inferred information, but not explicitly stated
      information, was uniquely predictive of reading comprehension after accounting
      for word decoding.

PMID- 24315375
TI  - SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks.
AB  - Reversible posttranslational modifications are emerging as critical regulators of
      mitochondrial proteins and metabolism. Here, we use a label-free quantitative
      proteomic approach to characterize the lysine succinylome in liver mitochondria
      and its regulation by the desuccinylase SIRT5. A total of 1,190 unique sites were
      identified as succinylated, and 386 sites across 140 proteins representing
      several metabolic pathways including beta-oxidation and ketogenesis were
      significantly hypersuccinylated in Sirt5(-/-) animals. Loss of SIRT5 leads to
      accumulation of medium- and long-chain acylcarnitines and decreased beta
      hydroxybutyrate production in vivo. In addition, we demonstrate that SIRT5
      regulates succinylation of the rate-limiting ketogenic enzyme 3-hydroxy-3
      methylglutaryl-CoA synthase 2 (HMGCS2) both in vivo and in vitro. Finally,
      mutation of hypersuccinylated residues K83 and K310 on HMGCS2 to glutamic acid
      strongly inhibits enzymatic activity. Taken together, these findings establish
      SIRT5 as a global regulator of lysine succinylation in mitochondria and present a
      mechanism for inhibition of ketogenesis through HMGCS2.

PMID- 24315377
TI  - Oncologic impact of anastomotic leakage in rectal cancer surgery according to the
      use of fibrin glue: case-control study using propensity score matching method.
AB  - BACKGROUND: The oncologic impact of anastomotic leakage after rectal cancer
      surgery remains controversial. METHODS: Between January 1999 and December 2010,
      1,148 patients with rectal cancer who underwent curative surgery with sphincter
      preservation were retrospectively reviewed. Using the propensity score matching
      method, 328 patients with fibrin glue were matched to 328 patients without fibrin
      glue, and oncologic outcomes were compared in the matched groups. RESULTS:
      Anastomotic leakage was diagnosed in 76 patients (6.6%). On multivariate
      analysis, fibrin glue was the independent predictor of prevention of anastomotic
      leakage. In the 656 matched groups, patients with anastomotic leakage had
      significantly worse 5-year local recurrence-free survival and disease-free
      survival than those without leakage. Multivariate analysis confirmed that
      anastomotic leakage was an independent prognostic factor of both local recurrence
      and disease-free survival, but the use of fibrin glue was not associated with the
      long-term outcomes when controlling for confounders. CONCLUSIONS: Anastomotic
      leakage is a major independent prognostic factor for long-term outcomes. Fibrin
      glue has a protective effect of anastomosis, without oncologic advantages.

PMID- 24315378
TI  - Rates and indications for surgical breast biopsies in a community-based health
      system.
AB  - BACKGROUND: High rates of surgical breast biopsies in community hospitals have
      been reported but may misrepresent actual practice. METHODS: Patient-level data
      from 5,757 women who underwent breast biopsies in a large integrated health
      system were evaluated to determine biopsy types, rates, indications, and
      diagnoses. RESULTS: Between 2008 and 2010, 6,047 breast biopsies were performed
      on 5,757 women. Surgical biopsy was the initial diagnostic procedure in 16% (n =
      942) of women overall and in 6% (72 of 1,236) of women with newly diagnosed
      invasive breast cancer. Invasive breast cancer was diagnosed in 72 women (8%)
      undergoing surgical biopsy compared with 1,164 (24%) undergoing core needle
      biopsy (P < .001, age adjusted). Main indications for surgical biopsies included
      symptomatic abnormalities, technical challenges, and patient choice. CONCLUSIONS:
      Surgical biopsy was the initial diagnostic procedure in 16% of women with breast
      abnormalities, comparable with rates at academic centers. Rates could be improved
      by more careful consideration of indications.

PMID- 24315379
TI  - Meta-analysis of sublay versus onlay mesh repair in incisional hernia surgery.
AB  - BACKGROUND: Incisional hernia (IH) remains a very frequent postoperative
      complication. The 2 techniques most frequently used are the onlay repair and
      sublay repair. However, it remains unclear which technique is superior. DATA
      SOURCES: A meta-analysis was conducted according to Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines. The quality of the nonrandomized
      studies was assessed using the Newcastle-Ottawa Scale. RESULTS: Of 178 articles,
      10 articles (2 randomized controlled trials, 1 prospective study, and 7
      retrospective studies) comprising a total of 1,948 patients (775 onlay operations
      and 1173 sublay operations) were selected. Two of the studies scored below 5
      points on the Newcastle-Ottawa Scale and were not selected. A trend was observed
      for IH recurrence in favor of sublay repair (odds ratio = 2.41; 95% confidence
      interval, .99 to 5.88; I(2) = 70%; P = .05). Surgical site infection occurred
      significantly less after sublay repair (odds ratio = 2.42; 95% confidence
      interval, 1.02 to 5.74; I(2) = 16%; P = .05). No difference was observed
      regarding seroma and hematoma. CONCLUSIONS: Although the majority of the included
      studies were retrospective studies, sublay repair seems the preferred technique
      for IH repair.

PMID- 24315380
TI  - Staged management of the open abdomen and enteroatmospheric fistulae using split
      thickness skin grafts.
AB  - BACKGROUND: Management of the open abdomen with polyglactin 910 mesh followed by
      split-thickness skin grafts allows safe, early closure of abdominal wounds. This
      technique can be modified to manage enteroatmospheric fistulae. Staged ventral
      hernia is performed in a less inflamed surgical field. METHODS: A retrospective
      review was performed of 59 consecutive patients who underwent abdominal skin
      grafting for open abdominal wounds from 2001 to 2011. RESULTS: The median length
      of follow-up was 215 days. Thirty-one percent of patients presented with
      preexisting enteroatmospheric fistulae, and 41% required polyglactin 910 mesh
      placement before skin grafting. Partial or complete skin graft failure occurred
      in 7 patients. Four patients required repeat skin grafting. All patients
      ultimately achieved abdominal wound closure, and none developed de novo fistulae.
      CONCLUSIONS: With proper technique, skin grafting of the open abdomen with a
      planned ventral hernia repair is a safe and effective alternative to delayed
      primary closure.

PMID- 24315381
TI  - Factors influencing clinical results in colon surgical resection: surgeon, volume
      of cases and now day of the week?

PMID- 24315382
TI  - The implementation of a surgeon-directed quality improvement strategy in breast
      cancer surgery.
AB  - BACKGROUND: The investigators designed a sustained, surgeon-directed, iterative
      project to improve the quality of breast cancer surgery in south central Ontario.
      METHODS: The strategy included audit and feedback of surgeon-selected quality
      indicators, workshops, and tailoring interviews. Workshops were held to discuss
      quality improvement strategies, select quality indicators, review audited
      results, and select interventions for subsequent implementation. Semistructured
      tailoring interviews were conducted to identify facilitators and barriers to
      improved quality. All presentations and results were disseminated to all surgeons
      performing breast surgery in the study region. RESULTS: Forty-four surgeons
      performing breast surgery across 12 hospitals are involved in the project. Five
      workshops have been held since 2005. Surgeons' enthusiasm and involvement in the
      project have been positive. Interim results demonstrated that over 4 audit cycles
      (2006-2010), the preoperative core biopsy rate increased from 73% to 92%. The
      tailoring interviews indicated that 18 of 21 surgeons performed preoperative core
      biopsies. CONCLUSIONS: This project highlights the feasibility of a surgeon
      directed, iterative quality improvement strategy in breast cancer surgery.
      Interim results demonstrate consistent improvements in a key selected quality
      indicator.

PMID- 24315383
TI  - Field evaluation of three blood-based assays for elk (Cervus canadensis)
      naturally infected with Mycobacterium bovis.
AB  - Diagnosis of Mycobacterium bovis in wild populations is very challenging due to
      complications imposed by the use of traditional skin tests, poor sensitivity of
      gold standard tests which rely on culture of M. bovis from tissues and wide
      variations in severity of disease. Various combinations of a lymphocyte
      stimulation test (LST), fluorescence polarization assay (FPA) and the Cervid TB
      Stat-Pak were evaluated using two different validation approaches: a latent class
      analysis and classical statistical approach using culture as a gold standard. A
      validation subsample consisting of animals culled for population control and
      mortalities from capture provided an unbiased estimate of test performance for
      comparison. The sensitivity of the LST (0.83, 95% CI: [0.70-0.97] as a single
      test was similar to existing tuberculin skin tests, but the sensitivity of the
      FPA (0.40, 95% CI: [0.22-0.58]) and Cervid TB Stat-Pak (0.62, 95% CI: [0.41
      0.83]) were lower in this population. Test performance of the LST and Cervid TB
      Stat-Pak in parallel was similar to the use of all three tests in parallel and
      inclusion of the FPA did not greatly enhance test performance. Prevalence of M.
      bovis in elk varied substantially between the high risk area of southern Manitoba
      (9.1%, 95% CI: [6.09-12.1%]) and lower risk areas outside this zone (0.76%, 95%
      CI: [0-2.26%]). Bayesian latent class analysis indicated lack of covariance
      between the two antibody tests (FPA and Cervid TB Stat-Pak) while the classical
      two-stage analysis indicated there was conditional dependence between the tests.
      All three tests when used in parallel resulted in 100% NPV using all three
      validation methods, indicating few elk were misclassified as false negative by
      post mortem culture. Similar to previous studies, this study found that
      combinations of blood tests that utilize cell mediated responses along with
      humoral antibody responses maximize the sensitivity of tests for diagnosis of M.
      bovis in wild cervid populations. 

PMID- 24315384
TI  - A comparison of the impact factor and the SCImago Journal Rank index in
      respiratory system journals.

PMID- 24315385
TI  - Using cells as biochemical test tubes: comment on "Biomolecular dynamics and
      binding studies in the living cell" by Stephan Diekmann and Christian Hoischen.

PMID- 24315386
TI  - Effect of copper on pro- and antioxidative reactions in radish (Raphanus sativus
      L.) in vitro and in vivo.
AB  - The generation of superoxide radicals, lipid peroxidation (as measured by malone
      dialdehyde formation) and the activity of selected antioxidant enzymes
      (superoxide dismutase, catalase, ascorbate peroxidase) were assessed in radish
      (Raphanus sativus L.), in response to elevated concentrations of copper ions in
      the culture medium in vitro and in vivo. Experiments were performed on 7-day-old
      seedlings and 5-week-old calluses grown on media supplemented with CuSO4 in
      concentrations of 10, 100 and 1000MUM. The exposure to elevated Cu concentrations
      in the medium significantly reduced both callogenesis and the proliferation of
      radish calluses in vitro. Cu treatment resulted in the increased generation of
      the superoxide radical (O2(-)) in radish seedlings and calluses indicating the
      occurrence of oxidative stress in radish cells, whereas the level of lipid
      peroxidation (LPO) remained unchanged. Both in calluses and in radish seedlings
      in vivo, the relative level of oxidative stress was maximal at micromolar Cu
      concentrations and became attenuated with increasing Cu concentrations. Stronger
      oxidative stress occurred in the radish seedlings in vivo, compared with radish
      calluses in vitro. The observed lower sensitivity of calluses to Cu-induced
      oxidative stress and their ability to proliferate upon exposure to Cu
      concentrations of up to 1000MUM demonstrate the potential of in vitro cell
      selection to obtain metal-tolerant radish plant lines. 

PMID- 24315387
TI  - Comment on "Biomolecular dynamics and binding studies in the living cell" by
      Stephan Diekmann and Christian Hoischen.

PMID- 24315388
TI  - The face of freedom: comment on "Consciousness in the universe. A review of the
      'Orch OR' theory" by Stuart Hameroff and Roger Penrose.

PMID- 24315389
TI  - A semi-automated 3-D annotation method for breast ultrasound imaging: system
      development and feasibility study on phantoms.
AB  - Spatial annotation is an essential step in breast ultrasound imaging, because the
      follow-up diagnosis and treatment are based on this annotation. However, the
      current method for annotation is manual and highly dependent on the operator's
      experience. Moreover, important spatial information, such as the probe tilt
      angle, cannot be indicated in the clinical 2-D annotations. To solve these
      problems, we developed a semi-automated 3-D annotation method for breast
      ultrasound imaging. A spatial sensor was fixed on an ultrasound probe to obtain
      the image spatial data. Three-dimensional virtual models of breast and probe were
      used to annotate image locations. After the reference points were recorded, this
      system displayed the image annotations automatically. Compared with the
      conventional manual annotation method, this new annotation system has higher
      accuracy as indicated by the phantom test results. In addition, this new
      annotation method has good repeatability, with intra-class correlation
      coefficients of 0.907 (average variation: <=3.45%) and 0.937 (average variation:
      <=2.85%) for the intra-rater and inter-rater tests, respectively. Breast phantom
      experiments simulating clinical breast scanning further indicated the feasibility
      of this system for clinical applications. This new annotation method is expected
      to facilitate more accurate, intuitive and rapid breast ultrasound diagnosis. 

PMID- 24315390
TI  - Quantification of acoustic radiation force impulse in differentiating between
      malignant and benign breast lesions.
AB  - The aim of this study was to evaluate the use of gray-level quantification (GLQ)
      in virtual touch tissue imaging (VTI) in the differential diagnosis of breast
      lesions. GLQ values of 153 lesions (101 benign, 52 malignant) were analyzed with
      matrix laboratory software (MATLAB, The MathWorks, Natick, MA, USA), with gray
      levels ranging from 0 (pure black) to 255 (pure white). The diagnostic
      performance of GLQ was also evaluated using receiver operating characteristic
      curve analysis. The mean GLQ value for benign lesions (103.27 +/- 39.44) differed
      significantly from that for malignant lesions (44.57 +/- 13.61) (p < 0.001). At a
      cutoff value of 52.31, the sensitivity, specificity, accuracy, positive
      predictive value and negative predictive value were 86.5%, 93.1%, 90.8%, 86.5%
      and 93.1%, respectively. In conclusion, we have proposed a method for
      quantification of gray levels in VTI for the differential diagnosis of breast
      lesions. Our results indicate that this method has the potential to aid in the
      classification of benign and malignant breast masses. 

PMID- 24315391
TI  - Tissue elasticity quantification by acoustic radiation force impulse for the
      assessment of renal allograft function.
AB  - Acoustic radiation force impulse (ARFI) quantification, a novel ultrasound-based
      elastography method, has been used to measure liver fibrosis. However, few
      studies have been performed on the use of ARFI quantification in kidney
      examinations. We evaluated renal allograft stiffness using ARFI quantification in
      patients with stable renal function (n = 52) and those with biopsy-proven
      allograft dysfunction (n = 50). ARFI quantification, given as shear wave velocity
      (SWV), was performed. The resistance index (RI) was calculated by pulsed-wave
      Doppler ultrasound, and clinical and laboratory data were collected. Morphologic
      changes in transplanted kidneys were diagnosed by an independent pathologist.
      Mean SWV was more significantly negatively correlated with estimated glomerular
      filtration rate (eGFR) (r = -0.657, p < 0.0001) than was RI (r = -0.429, p =
      0.0004) in transplanted kidneys. Receiver operating characteristic curve analysis
      revealed that the sensitivity and specificity of quantitative ultrasound in the
      diagnosis of renal allograft dysfunction were 72.0% and 86.5% (cutoff value =
      2.625), respectively. The latter values were better than those of RI, which were
      62.0% and 69.2% (cutoff value = 0.625), respectively. The coefficient of
      variation for repeat SWV measurements of the middle part of transplanted kidney
      was 8.64%, and inter-observer agreement on SWV was good (Bland-Altman method, ICC
      = 0.890). In conclusion, tissue elasticity quantification by ARFI is more
      accurate than the RI in diagnosing renal allograft function. 

PMID- 24315392
TI  - Peripheral enhancement of breast cancers on contrast-enhanced ultrasound:
      correlation with microvessel density and vascular endothelial growth factor
      expression.
AB  - There is little evidence of an association between peripheral enhancement on
      contrast-enhanced ultrasound and histopathologic prognostic factors in breast
      cancer. The purpose of our study was to investigate the relationship of
      peripheral enhancement on contrast-enhanced ultrasound with microvessel density,
      vascular endothelial growth factor (VEGF) expression and other prognostic factors
      in patients with breast cancer. In 51 patients with BI-RADS (Breast Imaging
      Reporting and Data System) category 5 lesions scheduled for surgery, contrast
      enhanced ultrasound with an 8-4 linear transducer and B-mode pulse inversion
      harmonic imaging was performed after administration of SonoVue. Forty-three
      histologically confirmed breast cancers were included in the study and divided
      into the peripheral enhancement group and non-peripheral enhancement group on the
      basis of their features on contrast-enhanced ultrasound. The ratio of peripheral
      to central microvessel density, VEGF expression, tumor size, histopathologic
      type, stage, lymph node metastasis and expression of estrogen receptor,
      progesterone receptor, c-erb-B2 and p53 were compared between the two groups. The
      ratio of peripheral to central microvessel density and a peripherally
      positive/centrally negative VEGF expression pattern were significantly higher in
      the peripheral enhancement group than in the non-peripheral enhancement group (t
      test, p = 0.023, and chi(2) test, p = 0.035, respectively). There were no
      significant differences in breast cancer size, histopathologic type, stage, lymph
      node metastasis or expression of estrogen receptor, progesterone receptor, c-erb
      B2 and p53 between the two groups (chi(2) test, p = 0.416, 0.877, 0.543, 0.124,
      0.453, 0.554, 0.350 and 0.479 respectively). The peripheral enhancement pattern
      of breast cancer on contrast-enhanced ultrasound may be valuable in the
      evaluation of peripheral/central tumor angiogenesis and VEGF expression. 

PMID- 24315393
TI  - Associations of sonographic abnormalities of the shoulder with various grades of
      biceps peritendinous effusion (BPE).
AB  - Bicipital peritendinous effusion (BPE), a common ultrasonographic finding of the
      long head of the biceps tendon, may be associated with shoulder joint
      derangement, but supporting evidence from large-scale studies is lacking. The aim
      of this cross-sectional study was to determine the strength of the association
      between BPE and sonographic abnormalities of the shoulder joint. We reviewed the
      sonographic reports of patients with suspected shoulder disorders investigated
      ultrasonographically between January 2011 and January 2012. BPE was graded
      according to its measured thickness as absent (<1 mm), mild (1-2 mm), moderate (2
      3 mm) or severe (>3 mm). The associations between BPE and sonographic
      abnormalities were examined using multinomial logistic regression adjusted for
      age, gender, affected side and clinical diagnosis of frozen shoulder. The
      prevalence rates of absent, mild, moderate and severe BPE among the 907 shoulders
      examined were 64.1%, 17.8%, 10.4% and 7.7%, respectively. Frozen shoulder was
      associated with mild BPE (relative risk [RR] vs. participants without BPE = 1.83,
      95% confidence interval [CI] = 1.28-2.50). Sonographic findings of biceps
      tendinopathy, subdeltoid bursitis and full-thickness tears of the supraspinatus
      tendon were significantly associated with the entire spectrum of BPE, whereas
      subscapularis tendon tears were significantly associated with moderate (RR =
      2.47, 95% CI = 1.29-4.69) and severe (RR = 3.11, 95% CI = 1.51-6.33) BPE. Severe
      BPE was associated with articular-sided partial-thickness tears of the
      supraspinatus tendon (RR = 14.32, 95% CI = 4.30-34.35), posterior recess effusion
      (RR, 7.98, 95% CI = 1.44-34.93) and biceps medial subluxation (RR = 7.25, 95% CI
      = 1.90-22.33). Our study indicates that BPE is related to various shoulder
      abnormalities and that the strengths of these associations depend on the severity
      of BPE. Clinicians encountering BPE should grade its severity and be alert for
      hidden lesions of the shoulder joint. 

PMID- 24315394
TI  - Diagnostic performance of ultrasound and ultrasound elastography with respect to
      physician experience.
AB  - The aim of this study was to compare the diagnostic performance of gray-scale
      ultrasound (US), elastography and a combination of gray-scale ultrasound and
      elastography (US-E) in differentiating benign and malignant thyroid nodules with
      respect to the level of physician experience. Three hundred fifty-eight patients
      with 367 thyroid nodules who underwent both gray-scale US and elastography, from
      November 2011 to January 2012, were included in this study. The diagnostic
      performance of US performed by experienced and less experienced physicians was
      compared. Comparisons of the diagnostic performance of US, elastography and US-E
      were evaluated for each group separately. Of 367 nodules, 121 were malignant and
      246 were benign. When we compared the diagnostic performance of the experienced
      and less experienced physician groups, specificity was statistically higher in
      the experienced physician group for both US alone (p = 0.001) and US-E (p =
      0.048). However, the experienced and less experienced physician groups did not
      differ significantly on other measures of diagnostic performance, regardless of
      modality. For the experienced physicians, the specificity and positive predictive
      value US were 88.0% and 76.8%, respectively; both of them were significantly
      higher than the corresponding values for US-E. For the less experienced
      physicians, specificity was significantly higher on elastography (93.8%) than on
      US (71.4%) (p < 0.001). However, diagnostic performance did not differ
      significantly between US and US-E for the less experienced physicians.
      Experienced physicians had superior specificity compared with less experienced
      physicians. The diagnostic performance of elastography and US-E was inferior
      compared with that of US alone, irrespective of the level of experience of the
      physician.

PMID- 24315396
TI  - Layer-specific radiofrequency ultrasound-based strain analysis in a porcine model
      of ischemic cardiomyopathy validated by a geometric model.
AB  - Local layer-specific myocardial deformation after myocardial infarction (MI) has
      not been studied extensively although the sub-endocardium is more vulnerable to
      ischemia and interstitial fibrosis deposition. Radiofrequency (RF) ultrasound
      based analysis could provide superior layer-specific radial strain estimation
      compared with clinically available deformation imaging techniques. In this study,
      we used RF-based myocardial deformation measurements to investigate layer
      specific differences between healthy and damaged myocardium in a porcine model of
      chronic MI. RF data were acquired epicardially in healthy (n = 21) and infarcted
      (n = 5) regions of a porcine chronic MI model 12 wk post-MI. Radial and
      longitudinal strains were estimated in the sub-endocardial, mid-wall and sub
      epicardial layers of the left ventricle. Collagen content was quantified in three
      layers of healthy and infarcted regions in five pigs. An analytical geometric
      model of the left ventricle was used to theoretically underpin the radial
      deformation estimated in different myocardial layers. Means +/- standard errors
      of the peak radial and longitudinal strain estimates of the sub-endocardial, mid
      wall and sub-epicardial layers of the healthy and infarcted tissue were: 82.7 +/-
      5.2% versus 39.9 +/- 10.8% (p = 0.002), 63.6 +/- 3.3% versus 38.8 +/- 7.7% (p =
      0.004) and 34.3 +/- 3.0% versus 35.1 +/- 5.2% (p = 0.9), respectively. The radial
      strain gradient between the sub-endocardium and the sub-epicardium had decreased
      12 wk after MI, and histologic examination revealed the greatest increases in
      collagen in the sub-endocardial and mid-wall layers. Comparable normal peak
      radial strain values were found by geometric modeling when input values were
      derived from the in vivo measurements and literature. In conclusion, the
      estimated strain values are realistic and indicate that sub-endocardial radial
      strain in healthy tissue can amount to 80%. This high value can be explained by
      the cardiac geometry, as was illustrated by geometric modeling. After MI, strain
      values were decreased and collagen content was increased in the sub-endocardial
      and mid-wall layers. Layer-specific peak radial strain can be assessed by RF
      strain estimation and clearly differs between healthy and infarcted tissue.
      Although the relationship between tissue stiffness and tissue strain is not
      strictly local, this novel technique provides a valuable way to assess layer
      specific regional cardiac function in a variety of myocardial diseases. 

PMID- 24315395
TI  - Ex Vivo characterization of canine liver tissue viscoelasticity after high
      intensity focused ultrasound ablation.
AB  - The potential of elasticity imaging to detect high-intensity focused ultrasound
      (HIFU) lesions on the basis of their distinct biomechanical properties is
      promising. However, information on the quantitative mechanical properties of the
      tissue and the optimal intensity at which to determine the best contrast
      parameters is scarce. In this study, fresh canine livers were ablated using
      combinations of ISPTA intensities of 5.55, 7.16 and 9.07 kW/cm(2) and durations
      of 10 and 30 s ex vivo, resulting in six groups of ablated tissues. Biopsy
      samples were then interrogated using dynamic shear mechanical testing within the
      range of 0.1-10 Hz to characterize the tissue's post-ablation viscoelastic
      properties. All mechanical parameters were found to be frequency dependent.
      Compared with unablated cases, all six groups of ablated tissues had
      statistically significant higher complex shear modulus and shear viscosity.
      However, among the ablated groups, both complex shear modulus and shear viscosity
      were found to monotonically increase in groups 1-4 (5.55 kW/cm(2) for 10 s, 7.16
      kW/cm(2) for 10 s, 9.07 kW/cm(2) for 10 s, and 5.55 kW/cm(2) for 30 s,
      respectively), but to decrease in groups 5 and 6 (7.16 kW/cm(2) for 30 s, and
      9.07 kW/cm(2) for 30 s, respectively). For groups 5 and 6, the temperature was
      expected to exceed the boiling point, and therefore, the decreased stiffening
      could be due to the compromised integrity of the tissue microstructure. Future
      studies will entail estimation tissue mechanical properties in vivo and perform
      real-time monitoring of tissue alterations during ablation. 

PMID- 24315397
TI  - In Vivo response to compression of 35 breast lesions observed with a two
      dimensional locally regularized strain estimation method.
AB  - The objective of this study was to assess the in vivo performance of our 2-D
      locally regularized strain estimation method with 35 breast lesions, mainly
      cysts, fibroadenomas and carcinomas. The specific 2-D deformation model used, as
      well as the method's adaptability, led to an algorithm that is able to track
      tissue motion from radiofrequency ultrasound images acquired in clinical
      conditions. Particular attention was paid to strain estimation reliability,
      implying analysis of the mean normalized correlation coefficient maps. For all
      lesions examined, the results indicated that strain image interpretation, as well
      as its comparison with B-mode data, should take into account the information
      provided by the mean normalized correlation coefficient map. Different trends
      were observed in the tissue response to compression. In particular, carcinomas
      appeared larger in strain images than in B-mode images, resulting in a mean
      strain/B-mode lesion area ratio of 2.59 +/- 1.36. In comparison, the same ratio
      was assessed as 1.04 +/- 0.26 for fibroadenomas. These results are in agreement
      with those of previous studies, and confirm the interest of a more thorough
      consideration of size difference as one parameter discriminating between
      malignant and benign lesions. 

PMID- 24315398
TI  - Association between respiratory mechanics and autonomic function in morbid
      obesity.
AB  - This study aimed to investigate the association between respiratory mechanics and
      autonomic modulation in morbidly obese patients. We evaluated 10 morbidly obese
      subjects (BMI=52.9+/-11.2kg/m(2)), aged 23-58 years. Assessment of respiratory
      mechanics was done by the forced oscillation technique (FOT), and cardiovascular
      autonomic function was recorded by heart rate variability analysis (HRV). The
      Pearson correlation coefficient was used to test the associations between
      respiratory mechanics and HRV variables. There were associations between the
      standard deviation of all RR intervals (SDNN) and airway resistance (Rm) (r=
      0.82; p=0.004), SDNN and respiratory system resistance (R0) (r=-0.79; p=0.006),
      root mean square of successive differences between adjacent normal RR intervals
      (rMSSD) and respiratory system resistance (R5) (r=-0.643; p=0.0451), rMSSD and R0
      (r=-0.64; p=0.047), and rMSSD and Rm (r=-0.658; p=0.039). We concluded that the
      airway and respiratory system resistances are negatively associated with
      parasympathetic activity in patients with morbid obesity.

PMID- 24315400
TI  - Tackling the challenges posed by the human dynamic system.

PMID- 24315399
TI  - Effects of OLV preconditioning and postconditioning on lung injury in
      thoracotomy.
AB  - OBJECTIVE: To observe the effects of intermittent one-lung ventilation (OLV)
      before and after surgery on the inflammatory cytokines and biomarkers of
      oxidative stress in serum of lung cancer patients undergoing open thoracotomy.
      METHODS: Between June 2011 to March 2012, 80 patients undergoing lobectomy were
      classified into four groups nonrandomly: Group A, control group; B, OLV
      preconditioning group; C, OLV postconditioning group; D, OLV preconditioning
      combined-with-postconditioning group. Neutrophil granulocyte (PMN), interleukin 6
      (IL-6), superoxide dismutase (SOD), and malondialdehyde (MDA) were assayed in
      plasma samples taken preoperatively (T1), intraoperatively (T2), and 2 hours
      postoperatively (T3). RESULTS: Comparison of T1 with T2 and T3 documented
      significant increase in MDA, PMN, and IL-6 levels and decrease in SOD in the
      control group (p < 0.01). Compared with the control group, the levels of IL-6 and
      MDA decreased and SOD increased significantly at T2 in the OLV preconditioning
      group, at T3 in the OLV preconditioning combined postconditioning group (p <
      0.05). CONCLUSION: Preconditioning of intermittent OLV before thoracotomy
      combined with postconditioning of intermittent returning two-lung ventilation
      after surgery maybe alleviate systematic inflammatory response and oxidative
      stress for lung cancer patients.

PMID- 24315401
TI  - 15th International Graphonomics Society Conference (IGS 2011).

PMID- 24315402
TI  - Motor control and human skill.

PMID- 24315403
TI  - New insights into the regulation of inflorescence architecture.
AB  - The architecture of inflorescences displays the spatiotemporal arrangement of
      flowers and determines plant reproductive success through affecting fruit set and
      plant interaction with biotic or abiotic factors. Flowering plants have evolved a
      remarkable diversity of inflorescence branching patterns, which is largely
      governed by developmental decisions in inflorescence meristems and their derived
      meristems between maintenance of indeterminacy and commitment to the floral fate.
      Recent findings suggest that regulation of inflorescence architecture is mediated
      by flowering time genes, Arabidopsis LSH1 and Oryza G1 (ALOG) family genes, and
      the interaction between the auxin pathway and floral meristem regulators. In this
      review, we discuss how the relevant new players and mechanisms account for the
      development of appropriate inflorescence structures in flowering plants in
      response to environmental and developmental signals. 

PMID- 24315404
TI  - A phase III randomized study comparing neoadjuvant chemotherapy with concurrent
      chemotherapy combined with radiotherapy for locoregionally advanced
      nasopharyngeal carcinoma: updated long-term survival outcomes.
AB  - OBJECTIVE: To determine whether concurrent chemoradiotherapy (CCRT) can improve
      survival rates compared to the neoadjuvant chemotherapy (NACT) regimen in
      locoregionally advanced nasopharyngeal carcinoma (NPC) patients. MATERIALS AND
      METHODS: A total of 338 patients with biopsy-proven NPC were randomly assigned to
      receive NACT followed by radical radiotherapy (RT) then adjuvant chemotherapy
      (AC) or CCRT followed by AC. RESULTS: With a median follow-up of 60 months, the 5
      year overall survival (OS) rate did not differ significantly between two groups
      (75.5% vs 79.4% in CCRT and NACT group respectively, P=0.47, HR=0.84, 95%CI 0.53
      1.33). Metastasis-free survival (MFS) rate was significantly improved by the CCRT
      (79.0% vs 86.9%, P=0.05, HR=0.59, 95%CI 0.35-1.00). Subgroup analysis indicated
      that the benefit of CCRT was derived from N0/N1 tumors (78.0% vs 93.5%, P=0.05,
      HR=0.35, 95%CI 0.12-0.99). Higher rates of mucositis (52.4% vs. 35.9% P=0.02) and
      vomiting (13.7% vs. 4.7% P=0.00) were noted in the CCRT arm. Late toxicities were
      similar in two groups. CONCLUSIONS: The updated results demonstrated no
      significant survival benefit of CCRT over NACT in patients with locoregionally
      advanced NPC. CCRT only showed significant MFS efficacy in T3-4N0-1 populations.

PMID- 24315405
TI  - Electron microscopic evaluation of internal thoracic artery endothelial
      morphology in diabetic coronary bypass patients.
AB  - BACKGROUND: Diabetes is a well- identified major risk factor for cardiovascular
      diseases. This study was performed to evaluate the effect of diabetes and impact
      of glycemic control on internal thoracic artery (ITA) morphology by electron
      microscopy. METHODS: Thirty patients scheduled for coronary artery bypass
      grafting were enrolled in this study. Samples of ITA were taken during the
      surgery for electron microscopic evaluation. Group I (n = 10) consisted of
      diabetics who have poor glycemic control (HbA1c > 7.5%), group II (n = 10) of
      well-regulated (HbA1c = 4.4% to 6.2%) diabetic patients, and group III (n = 10)
      of nondiabetic patients. Samples were prepared as ultrathin sections and an
      original semiquantitative method of scoring was applied to describe the
      morphologic changes of endothelium. Final scores were analyzed with analysis of
      variance and post hoc analysis. RESULTS: In group I large vacuoles, swollen
      mitochondria were seen in endothelial cells and subendothelial edema was
      prominent. Endothelia (2.5 +/- 1.2), arterial wall (2.0 +/- 0.0), and endothelial
      mitochondria (2.9 +/- 1.3) scores of group I were significantly higher than the
      other 2 groups (p < 0.001). The samples of group II and group III did not show
      significant differences with each other. The correlation between HbA1c values and
      total endothelial scores statistically significant (r = 0.912; p < 0.001).
      CONCLUSIONS: There is a correlation between HbA1c values and morphologic changes
      of ITA graft. Uncontrolled diabetes is an important predictor of morphologic
      changes evidenced by the ultrastructural findings. These ultrastructural changes
      were not as prominent in the diabetes mellitus patients with well controlled
      metabolic statuses and patients without diabetes.

PMID- 24315406
TI  - Resident awareness of documentation requirements and reimbursement: a multi
      institutional survey.
AB  - BACKGROUND: The current economic environment necessitates efforts to prevent
      avoidable losses in clinical revenue in academic cardiothoracic surgery programs.
      Inadequate documentation frequently results in delayed, denied, or reduced
      reimbursement. With the recent increase in integrated residency programs,
      documentation and compliance are becoming increasingly dependent on junior
      residents; however, their understanding of reimbursement and documentation
      guidelines is currently unknown. METHODS: An electronically distributed, multi
      institutional survey of 6 general and subspecialty surgery programs was conducted
      consisting of open-ended numeric estimation of Medicare reimbursement for various
      levels of patient encounters. Closed-ended questions were used to assess resident
      knowledge of documentation requirements, accompanied by self-estimated compliance
      with those requirements. RESULTS: Thirty-seven percent (n = 106) of residents
      completed the survey. Most residents (77%) believe they play the primary role in
      documentation; however, knowledge of and compliance with higher level
      documentation practices range from 19% to 78% and 41% to 76%, respectively. On
      average, residents overestimate Medicare reimbursement of lower level encounters
      by as much as 77% and underestimate higher level encounters by as much as 38%. In
      many cases, the standard deviation of residents' estimates approaches the actual
      reimbursement value. CONCLUSIONS: Residents have a limited knowledge of
      documentation requirements. Self-reported compliance, even when guidelines are
      known, is low. Estimation of financial reimbursement is extremely variable.
      Residents overestimate reimbursement of lower level encounters and
      underappreciate reimbursement at higher levels. Ensuring appropriate
      reimbursement for services rendered will require formal cardiothoracic resident
      education and ongoing quality control.

PMID- 24315407
TI  - Marijuana and self-regulation: examining likelihood and intensity of use and
      problems.
AB  - It is important to understand the individual differences that contribute to
      greater frequency or intensity of marijuana use, or greater frequency of
      experiencing marijuana-related problems. The current study examined several
      elements of behavioral and emotional self-regulation as predictors of the
      likelihood and intensity of both marijuana use and marijuana-related problems. As
      predicted, indices of behavioral self-regulation (self-control, sensation
      seeking) were better predictors of marijuana use, while indices of emotional self
      regulation (affect, distress tolerance, and emotional instability) better
      predicted marijuana-related problems. Surprisingly, urgency was not related to
      use but was predictive of problems, and there were no significant interactions
      between behavioral and emotional self-regulation in predicting either use or
      problems. From these findings we conclude that while behavioral dysregulation may
      put individuals at risk for using marijuana, or using it more frequently, it is
      those individuals with difficulty in emotional self-regulation that are at risk
      for experiencing negative consequences as a result of their marijuana use.
      Clinically, these data are relevant; clinicians might focus more on addressing
      emotional regulation in order to lessen or eliminate the consequences of
      marijuana use. 

PMID- 24315408
TI  - [Influence of distinct criteria for selecting patients for swabbing on estimation
      of the effectiveness of the influenza vaccine].
AB  - OBJECTIVE: To estimate the effectiveness of the influenza vaccine under different
      criteria for selecting patients for swabbing. METHOD: A case-control study was
      performed of laboratory-confirmed cases (n=909) and negative controls for
      influenza (n=732) in the 2010-2011 to 2012-2013 seasons in Navarre (Spain). The
      adjusted vaccine effectiveness was estimated by including all swabs from patients
      with influenza-like-illness and selecting only the first two cases per physician
      and week. RESULTS: The first two patients per physician and week were less
      frequently vaccinated against influenza (7.9% vs. 12.5%, p=0.021) and less often
      received confirmation of influenza (53.6% vs. 66.4%, p <0.001) than subsequent
      patients. These differences decreased after adjustment for covariates. The
      effectiveness of the influenza vaccine was 49% (95% CI: 23-66%) when all swabs
      were included and was 55% (95% CI: 27-72%) when we selected the first two swabs
      per week and physician. CONCLUSION: The selection of the first two patients per
      physician and week may bias assessment of the effectiveness of the influenza
      vaccine, although this bias was small in the seasons analyzed.

PMID- 24315409
TI  - [Healthy habits and osteoporosis prevention in perimenopausal women from rural
      areas].
AB  - OBJECTIVE: The probability of developing osteoporosis decreases with an adequate
      supply of vitamin D, a balanced diet, and increased physical activity. In this
      study, we evaluated whether an educational intervention improves osteoporosis
      related behavior in perimenopausal women from rural areas. METHODS: A randomized
      experimental evaluation was performed of an educational intervention. The
      variables were physical activity, calcium intake and sun exposure in women from
      rural areas aged 45-54 years (n=216) at time 0 and 12 months after the
      educational intervention. In the control group (n=106), the information was sent
      by surface mail (month 0). In the intervention group (n=110), two interactive
      workshops were given (month 0). The topic of the workshops and the information
      sent by surface mail was healthy habits for osteoporosis prevention. RESULTS:
      After 12 months, the intervention group, but not the control group, had increased
      their physical activity (p=0.006), sun exposure (p=0.029), and calcium intake
      (53% to 64%). CONCLUSION: A simple educational intervention in perimenopausal
      women from rural areas improved healthy habits for osteoporosis prevention.

PMID- 24315410
TI  - Postnatal fluoxetine-evoked anxiety is prevented by concomitant 5-HT2A/C receptor
      blockade and mimicked by postnatal 5-HT2A/C receptor stimulation.
AB  - BACKGROUND: Postnatal treatment with the selective serotonin reuptake inhibitor
      fluoxetine, evokes anxiety and depressive behavior in rodent models in adulthood.
      We examined the role of serotonin 2A (5-HT2A), serotonin 2C (5-HT2C) and
      serotonin 1A (5-HT1A) receptors, implicated in the development of anxiety, in the
      behavioral consequences of postnatal fluoxetine (PNFlx). METHODS: Control and
      PNFlx rat pups received concomitant treatment with the 5-HT2A/C receptor
      antagonist, ketanserin, the 5-HT2A receptor antagonist, MDL100907, the 5-HT2C
      receptor antagonist, SB242084, or the 5-HT1A receptor antagonist, WAY-100635, and
      were tested for behavior in adulthood. The effect of postnatal treatment with the
      5-HT2A/C receptor agonist, DOI, on anxiety behavior was examined in adulthood.
      RESULTS: Postnatal 5-HT2A/C receptor blockade prevented PNFlx-evoked anxiety,
      attenuated depressive behavior, and normalized specific gene expression changes
      in the prefrontal cortex. Postnatal, selective 5-HT2A receptor antagonist
      treatment blocked PNFlx-evoked anxiety and depressive behavior, whereas 5-HT2C
      receptor antagonist treatment prevented anxiety but not depressive behavior.
      Postnatal 5-HT2A/C receptor stimulation was sufficient to evoke anxiety in
      adulthood. Serotonin 1A receptor blockade did not alter PNFlx-evoked anxiety but
      resulted in anxiety in control animals, an effect attenuated by concomitant 5
      HT2A/C receptor blockade. CONCLUSIONS: Postnatal fluoxetine-evoked anxiety and
      depressive behavior, as well as specific gene expression changes in the
      prefrontal cortex, were prevented by 5-HT2A/C receptor blockade. Adult anxiety
      was evoked by either 5-HT2A/C receptor stimulation or 5-HT1A receptor blockade of
      naive control pups. Our findings implicate serotonin 2 receptors in the
      development of perturbed emotionality following PNFlx and suggest that an altered
      balance of signaling through 5-HT1A and 5-HT2A/C receptors in early life
      influences anxiety behavior.

PMID- 24315412
TI  - Urban air pollution & its assessment in Lucknow City--the second largest city of
      North India.
AB  - Investigations were carried out during the summer season (March-June 2012) to
      observe the quality of indoor air by monitoring the levels of some selected air
      pollutants at 15 different houses covering the urban areas of Lucknow City.
      Concentrations of CO2, CO, PM10, PM2.5, SO2 and NO2 were monitored indoors and
      outdoors simultaneously and I/O ratios were calculated. Regression analysis for
      I/O relationship was performed to assess the contribution of outdoor sources to
      indoor air quality. Air Quality Index (AQI) for indoor air was also calculated to
      have an idea about the quality of indoor air and their health effects. In
      collaboration with the medical college doctors of the city, we surveyed 197
      persons to find out different diseases/symptoms being faced due to indoor air
      pollution. Results of the study revealed that the average levels of PM10 and
      PM2.5 were above the permissible limits laid by WHO at densely populated and
      roadside sites with 189 MUg/m(3) (PM2.5 76 MUg/m(3)) and 226 MUg/m(3) (PM2.5 91
      MUg/m(3)) respectively. Correlation analysis showed positive results. At sites
      like Alambagh and Chowk, the indoor AQI range was alarming with the values of 302
      and 209. Survey results also showed that 46% of urban people suffered from acute
      respiratory infections like bronchial asthma, headache, depression and dizziness
      and these people were mostly from Roadside colonies.

PMID- 24315411
TI  - Diagnosis and management of behavioral variant frontotemporal dementia.
AB  - Frontotemporal dementia was documented over a century ago. The last decade,
      however, has seen substantial changes in our conceptions of this increasingly
      recognized disorder. Different clinical variants have been delineated, the most
      common of which is the behavioral variant (bvFTD). Updated diagnostic criteria
      have been established. New histopathological findings and genetic etiologies have
      been discovered. Research continues to uncover molecular mechanisms by which
      abnormal proteins accumulate in degenerating brain tissue. Novel neuroimaging
      techniques suggest that functional networks are diminished in bvFTD that might be
      relevant to empathy and social behavior. Despite rapid advances in our
      understanding of bvFTD, the disease is still under-recognized and commonly
      misdiagnosed. The result is inappropriate patient care. Recognizing the various
      presentations of bvFTD and its histological and genetic subtypes might further
      diagnosis, treatment, and research. 

PMID- 24315413
TI  - Mineralocorticoid receptor blockade in addition to angiotensin converting enzyme
      inhibitor or angiotensin II receptor blocker treatment: an emerging paradigm in
      diabetic nephropathy: a systematic review.
AB  - Blockade of the renin-angiotensin-aldosterone system (RAAS) is a standard
      therapeutic intervention in diabetic patients with chronic kidney disease (CKD).
      Concomitant mineralocorticoid receptor blockade has been studied as a novel
      approach to further slow down CKD progression. We used PubMed and EMBASE
      databases to search for relevant literature. We included in our review eight
      studies in patients of at least 18 years of age, with a diagnosis of type 1 or
      type 2 diabetes mellitus and diabetic nephropathy, under an angiotensin
      converting enzyme inhibitor (ACEI) and/or an angiotensin II receptor blocker
      (ARB) as standard treatment. A subset of patients in each study also received a
      mineralocorticoid receptor blocker (MRB) (either spironolactone or eplerenone) in
      addition to standard treatment. Combined treatment with a mineralocorticoid
      receptor blocker further reduced albuminuria by 23 to 61% compared with standard
      treatment. Estimated glomerular filtration rate values upon study completion
      slightly decreased under combined treatment. Blood pressure levels upon study
      completion were significantly lower with combined treatment in three studies.
      Hyperkalemia prevalence increased in patients under combined treatment raising
      dropout rate up to 17%. Therefore, combined treatment by an ACEI/ARB and a MRB
      may further decrease albuminuria in diabetic nephropathy. This effect may be due
      to the specific properties of the MRB treatment. Clinicians should regularly
      check potassium levels because of the increased risk of hyperkalemia. Available
      evidence should be confirmed by an adequately powered comparative trial of the
      standard treatment (ACEI or ARB) versus combined treatment by an ACEI/ARB and a
      MRB.

PMID- 24315415
TI  - [Multiple endocrine neoplasia: familiar and spontaneous diagnosis].

PMID- 24315416
TI  - [Delayed development of multiple supernumerary teeth in a patient with juvenile
      myasthenia gravis treated with azathioprine].

PMID- 24315414
TI  - Functional characterization of a novel FGFR1OP-RET rearrangement in hematopoietic
      malignancies.
AB  - The RET (REarranged during Transfection) receptor tyrosine kinase is targeted by
      oncogenic rearrangements in thyroid and lung adenocarcinoma. Recently, a RET
      (exon 12) rearrangement with FGFR1OP [fibroblast growth factor receptor 1 (FGFR1)
      oncogene partner] (exon 12) was identified in one chronic myelomonocytic leukemia
      (CMML) patient. We report the molecular cloning and functional characterization
      of a novel FGFR1OP (exon 11)-RET (exon 11) gene fusion event (named FGFR1OP-RET),
      mediated by a reciprocal translocation t(6; 10)(q27; q11), in a patient affected
      by primary myelofibrosis (PMF) with secondary acute myeloid leukemia (AML). The
      FGFR1OP-RET fusion protein displayed constitutive tyrosine kinase and
      transforming activity in NIH3T3 fibroblasts, and induced IL3-independent growth
      and activation of PI3K/STAT signaling in hematopoietic Ba/F3 cells. FGFR1OP-RET
      supported cytokine-independent growth, protection from stress and enhanced self
      renewal of primary murine hematopoietic progenitor and stem cells in vitro. In
      vivo, FGFR1OP-RET caused a spectrum of disease phenotypes, with >50% of mice
      showing a fatal myeloproliferative disorder (MPD). Other phenotypes were leukemia
      transplantable in secondary recipients, dramatic expansion of the mast cell
      lineage, and reduction of repopulating activity upon lethal irradiation. In
      conclusion, FGFR1OP-RET chimeric oncogenes are endowed with leukemogenic
      potential and associated to myeloid neoplasms (CMML and PMF/AML).

PMID- 24315417
TI  - [Invasive disease due to Neisseria meningitidis serogroup 29E and C5 deficiency].

PMID- 24315418
TI  - [Prenatal diagnosis and management of bronchogenic cyst].

PMID- 24315419
TI  - [Descriptive study of malaria cases in a general hospital in Madrid between 1996
      and 2011].
AB  - INTRODUCTION: Malaria causes around 863,000 deaths per year, mostly of them in
      children under 5 years old. MATERIAL AND METHODS: We have reviewed the
      epidemiological data of malaria cases in a pediatric department in a Hospital in
      the Community of Madrid, in the period 1996-2011. RESULTS: In the period
      reviewed, 103 cases of malaria were diagnosed in children under 14 years old.
      Sixty percent were males and the average age was 4.5 years. In most cases, the
      infection arose during a visit to relatives in the country of origin. The vast
      majority did not have malaria prophylaxis. Twenty-five percent of the cases were
      diagnosed as complicated malaria, the main criteria being hyperparasitemia, of
      which 80% of the patients did not present any other complications CONCLUSIONS: A
      high level of suspicion must be maintained in any patient who comes from a
      malaria endemic area. The key factor responsible for the infection was the lack
      of chemoprophylaxis.

PMID- 24315420
TI  - [Valproate-induced hyperammonemic encephalopathy in a neonate: treatment with
      carglumic acid].
AB  - Valproate-induced hyperammonemic encephalopathy (VHE) is an unusual and serious
      complication of valproate (VA) treatment. When an early diagnosis is made, it can
      be reversed with VA withdrawal and early treatment for hyperammonemia. We
      describe the case of a 20 days old male, who developed a serious VHE after
      receiving VA for refractory neonatal seizures. The VHE was resolved with VA
      withdrawal in association with carglumic acid and other measures for
      hyperammonemia treatment. 

PMID- 24315421
TI  - [Extreme reactive thrombocytosis in a healthy 6 year-old child].
AB  - Thrombocytosis is usually a casual finding in children. Reactive or secondary
      thrombocytosis is the more common form, being the infections diseases the most
      prevalent cause of it. Regarding the number of platelets there are four degrees
      of thrombocytosis; in its extreme degree the number of platelets exceeds
      1,000,000/mm(3). We describe a case of extreme reactive thrombocytosis in a
      healthy 6-year-old child. He required critical care admission for diagnosis and
      treatment (maximum number of platelets 7,283,000/mm(3)). We review the different
      causes of thrombocytosis in childhood, the differential diagnosis, and the
      available treatments in case of extreme thrombocytosis. 

PMID- 24315422
TI  - [A case of ciguatera poisoning in a paediatric patient].

PMID- 24315423
TI  - [Effect of freezing on the "creamatocrit" measurement of the lipid content of
      human donor milk].
AB  - OBJECTIVE: To determine, by the creamatocrit measurement, the effect on the fat
      content of raw and pasteurized donor milk of freezing during 3 months at -20 
      degrees C. METHODS: The evolution of the creamatocrit measurement (following
      Lucas technique) on frozen (-20  degrees C), raw and pasteurized human milk, was
      analyzed during 3 months. RESULTS: The fat content of raw milk (n=44) was 3.19
      g/dl at the beginning and 2.86 g/dl after 3 months frozen (p=0.02). In
      pasteurized milk (n=36) fat content at the first determination was 2.59 g/dl and
      2.20 g/dl after 1 month frozen (p=0.01). Afterwards there were no significant
      changes up to 3 months frozen. Variability was observed in the intermediate
      values. CONCLUSIONS: A reduction on the fat content measurement of raw and
      pasteurized donor human milk after freezing was observed. Freezing does not
      inactivate the milk lipase but does destroy the fat globule. Creamatocrit
      measurement may not be the best method to determine the fat content of processed
      human milk.

PMID- 24315424
TI  - [Immigration and factors associated with breastfeeding. CALINA study].
AB  - OBJECTIVE: To identify socio-cultural, obstetric and perinatal characteristics
      associated with complete breastfeeding (CBF) during the first 4 months of age,
      depending on maternal origin. MATERIAL AND METHODS: Socio-cultural, obstetric and
      perinatal aspects associated with breastfeeding depending on maternal origin were
      evaluated in a longitudinal study in a representative infant population from
      Aragon (n = 1452). RESULTS: The prevalence of CBF was higher in immigrant mothers
      than in those from Spain. CBF was maintained in 37.2% of mothers from Spain at 4
      months, compared with 43% of immigrants (P=.039) (RR Spanish/immigrants=0.76; 95%
      CI: 0.58-0.99); at 6 months this occurred in 13.9% vs. 23.8%, respectively
      (P<.001) (RR Spanish/immigrants=0.52; 95% CI: 0.37-0.72). The factors associated
      with CBF at 4 months are different between both groups. Mothers born in Spain are
      older (P=.002), have higher academic level (P=.001), greater parity (P=.003), and
      a higher probability of vaginal delivery (P=.005); and their children have the
      highest anthropometric values at birth. However, in immigrant mothers, the
      maintenance of CBF was associated with a higher maternal body mass index and with
      working at home. In both groups, CBF remains more frequently in those mothers who
      do not smoke (P=.001). CONCLUSIONS: The prevalence of CBF during the first months
      of life is higher in immigrant mothers than in those from Spain, and socio
      cultural, obstetric and perinatal factors are different, depending on maternal
      origin.

PMID- 24315425
TI  - [To quantify research in paediatric emergencies. Author's reply].

PMID- 24315426
TI  - [Time of cord clamping and neonatal complications, a prospective study].
AB  - OBJECTIVE: To assess the effects of early or late clamping of the umbilical cord
      in term newborns, assessing the levels of hemoglobin, hematocrit, and ferritin,
      and their correlation with some of the complications. PATIENTS AND METHODS: A
      prospective study of healthy newborns at term or born by dystotic or eutocic
      delivery in our hospital between May 2009 until May 2010. Patients were assigned
      according to the time of clamping, group 1 (<60 seconds), group 2 (1 to<2
      minutes), and group 3 (2 to 3 minutes). Laboratory tests were performed at birth
      and at 48 hours of life, assessing the levels of hemoglobin, hematocrit,
      ferritin, and bilirubin. The risk of polycythemia, respiratory distress syndrome,
      neonatal phototherapy or admission to the Intensive Care Unit and the hospital
      stay, were evaluated. RESULTS: A total of 242 patients were included: group 1
      (g1=80), group 2 (g2=31) y group 3 (g3=131). The background maternal and neonatal
      characteristics were similar in all sets. The first test showed significant
      differences in ferritin levels in those infants with delayed clamping (g1: 111
      mg/dl, g2: 125 mg/dl, g3: 173 mg/dl; p<0.01). In the second analysis the values
      of hemoglobin (g1: 17.3 g/dl, g2: 18.9 g/dl, g3: 19.2 g/dl; p<0.01), hematocrit
      (g1: 53.4%, g2: 58%, g3: 59%; p<0.01) and ferritin (g1: 254 mg/dl, g2: 254.7
      mg/dl, g3: 313 mg/dl; p = 0.008) were statistically higher in this group. As
      regards complications, a significant increase was observed in the number of cases
      of polycythemia symptoms in group 3. CONCLUSIONS: The late cord clamping is
      associated with an increase in hematocrit, hemoglobin and ferritin at 48 hours of
      life, as well as an increased risk of polycythemia present with symptoms.

PMID- 24315427
TI  - Papillomavirus vaccination in France according to 2008 to 2012 Vaccinoscopie((r))
      data.
AB  - Vaccination against human papillomavirus infections (HPV), introduced in the
      French vaccinal schedule in 2007, was recommended until the end of 2012 for 14
      year-old girls, with a catch-up policy until 23years of age. We followed the
      evolution of this vaccine coverage rate (VC) during these 5years in the
      Vaccinoscopie((r)) survey. METHOD: We present the analysis of data collected in
      2012 from a sample of 1136 mothers of girls 14 to 16years of age. They answered a
      self-administered questionnaire on Internet and reported all vaccinations
      mentioned in their daughter's health record. RESULTS: In 2012, respectively
      12.9%, 33.6%, and 48.1% of girls 14, 15 and 16years of age had begun HPV
      vaccination (>=1 dose received) and respectively 4.3%, 23.6%, and 40.5% of them
      had received a complete vaccination schedule (3 doses), i.e. 31.7% of 14-16-year
      old girls had started the vaccination schedule and 22.9% were fully vaccinated.
      VC for >=1 dose had decreased between 2009 and 2012 (-14 points in 14-year-old
      girls, -16 points in 15-year-old girls, and -11 points between 2009 and 2012 in
      16-year-old girls). Regional VCs were heterogeneous. CONCLUSION: HPV VC is
      clearly insufficient. It is essential that physicians concerned by HPV
      vaccination be mobilized and take every opportunity to inform, reassure, and
      vaccinate teenage girls. HPV vaccination has been recommended for girls between
      11 and 14years of age since 2013, which could help improve adherence to
      vaccination.

PMID- 24315428
TI  - Salvage therapy of small volume prostate cancer nodal failures: a review of the
      literature.
AB  - New imaging modalities may be useful to identify prostate cancer patients with
      small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to
      local treatments (radiotherapy, surgery) with the aim of long-term control of the
      disease, even in a condition traditionally considered prognostically unfavorable.
      This report reviews the new diagnostic tools and the main published data about
      the role of surgery and radiation therapy in this particular subgroup of
      patients. 

PMID- 24315429
TI  - The desire for children and fertility issues among young German cancer survivors.
AB  - PURPOSE: For young cancer patients, family planning is not always completed at
      the time of cancer diagnosis. This study investigated young cancer patients'
      desire to have children, its intensity, and their discussion with oncologists and
      fertility specialists about fertility. Furthermore, gender differences,
      differences between childless patients and patients with children, and
      correlations with psychological distress were analyzed. METHODS: A total of 149
      cancer patients (range, 18-45 years of age) answered a self-developed
      questionnaire. Psychological distress was measured with the Patient Health
      Questionnaire. RESULTS: Seventy-four percent of patients had a desire to have
      children at the time of diagnosis. Whereas the intensity of the desire for
      children increased pre- to post-treatment in childless patients, it decreased in
      patients who already had children. A total of 55 patients who wanted a child
      (50%) needed supportive care concerning this issue; 60% of the total sample had
      discussed fertility aspects with their oncologists and 20% with fertility
      specialists. Patients reported higher levels of satisfaction with their
      discussions with fertility specialists than with their discussions with
      oncologists. Men (56%) underwent fertility preservation more often than did women
      (31%). Female sex was the only variable predicting psychological distress,
      whereas parenthood, fertility preservation, and desire for children had no
      significant impact. CONCLUSIONS: The desire to have children and the fertility
      issues involved are important for young cancer patients. Reasons for not
      discussing fertility aspects with oncologists and the cause of low referral rates
      to fertility specialists should be explored in future studies. The implementation
      of structured psychosocial supportive care might address the needs of highly
      fertility-distressed patients.

PMID- 24315430
TI  - A longitudinal study of the risks for introduction of severe footrot into sheep
      flocks in the south west of Norway.
AB  - In 2008, ovine footrot was detected in Norway for the first time since 1948. By
      December 2012 it had spread to 99 flocks, all in the county of Rogaland in the
      south west of Norway, and 42% of which were located in the municipality of
      Rennesoy in Rogaland. The aim of this study was to investigate risk factors for
      contracting severe footrot in flocks of sheep. A flock was considered positive
      for severe footrot based on positive virulence test or by clinical signs in
      addition to a positive PCR test. A retrospective longitudinal study was performed
      with a questionnaire as the main data source. All sheep farmers (107) in the
      municipality of Rennesoy were selected for inclusion in the study. The questions
      focused on direct and indirect contacts between sheep in different sheep flocks
      and general information about the farm. The questions covered the years 2007
      2011. Data were analysed using discrete time survival modelling. A total of 81
      (76%) farmers responded to the questionnaire including 29 of 41 (71%) farmers
      with flocks positive for severe footrot. Factors that increased the risk of a
      flock becoming positive for severe footrot in the final multivariable survival
      model were sheep that trespassed boundary fences and came into contact with a
      flock positive for severe footrot (odds ratio 11.5, 95% confidence interval 4.1
      32.2) and at least one flock with severe footrot within 0-1km radius of a farm
      (odds ratio 8.6, 95% confidence interval 2.3-32.6). This study highlights the
      importance of upgrading and maintaining boundary fences and encouraging farmers
      to avoid direct and indirect contact between nearby flocks. 

PMID- 24315432
TI  - The global risk of bladder cancer: let's just do something about it!

PMID- 24315431
TI  - 'Particle genetics': treating every cell as unique.
AB  - Genotype-phenotype relations are usually inferred from a deterministic point of
      view. For example, quantitative trait loci (QTL), which describe regions of the
      genome associated with a particular phenotype, are based on a mean trait
      difference between genotype categories. However, living systems comprise huge
      numbers of cells (the 'particles' of biology). Each cell can exhibit substantial
      phenotypic individuality, which can have dramatic consequences at the organismal
      level. Now, with technology capable of interrogating individual cells, it is time
      to consider how genotypes shape the probability laws of single cell traits. The
      possibility of mapping single cell probabilistic trait loci (PTL), which link
      genomic regions to probabilities of cellular traits, is a promising step in this
      direction. This approach requires thinking about phenotypes in probabilistic
      terms, a concept that statistical physicists have been applying to particles for
      a century. Here, I describe PTL and discuss their potential to enlarge our
      understanding of genotype-phenotype relations. 

PMID- 24315433
TI  - Inducing cellular aging: enabling neurodegeneration-in-a-dish.
AB  - The immaturity of neurons differentiated from human induced pluripotent stem
      cells (hiPSCs) presents difficulties for modeling late-onset neurodegenerative
      disorders such as Parkinson's disease. Now, Miller et al. (2013) provide a
      strategy for inducing aging-related phenotypes in hiPSC-derived neurons, enabling
      in vitro study of late-onset neurodegenerative diseases.

PMID- 24315434
TI  - The young and the Wnt-less: transplantable fetal intestinal spheroids without
      Wnts.
AB  - The differences between fetal and adult intestinal stem cells are unclear, and
      understanding this relationship could present novel therapeutic opportunities.
      Fordham et al. (2013) and Mustata et al. (2013) report a potential source of
      transplantable epithelial cells from fetal gut that can convert into adult
      intestinal stem and differentiated cells.

PMID- 24315435
TI  - The "skinny" on Wnt signaling in stem cells.
AB  - Although previous reports suggested that canonical Wnt signaling has opposing
      effects on epidermal and hair follicle stem cells, two recent papers (Choi et
      al., 2013; Lim et al., 2013) now show that Wnt signaling promotes proliferation
      in both stem cell populations, revealing new insights into regeneration of both
      skin compartments.

PMID- 24315436
TI  - Who needs stem cells if you can dedifferentiate?
AB  - Regenerative mechanisms involving either stem cell differentiation or
      dedifferentiation of mature cells have been described in various systems, but the
      relationship between such disparate mechanisms is unclear. Two recent papers, one
      by Sandoval-Guzman et al. (2013) and one by Tata et al. (2013), address
      fundamental questions about the universality of reparative regeneration and
      whether mammals share any properties seen in lower vertebrates.

PMID- 24315437
TI  - Noncanonical Wnt comes of age in hematopoietic stem cells.
AB  - Understanding molecular mechanisms of aging is crucial in efforts to reverse it.
      In a recent issue of Nature, Florian et al. (2013) report that increasing levels
      of noncanonical Wnt signaling accompany hematopoietic stem cell (HSC) aging,
      which can be modulated to functionally rejuvenate HSCs.

PMID- 24315438
TI  - Oversight for clinical uses of autologous adult stem cells: lessons from
      international regulations.
AB  - Autologous adult stem cells (ASCs) are being administered by physicians for
      indications that have not been demonstrated as safe and effective in formal
      clinical trials. Examination of regulatory frameworks across five countries
      suggests that balancing the demands of research with clinical freedom has created
      structural weaknesses that are being exploited. 

PMID- 24315439
TI  - Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of
      cystic fibrosis patients.
AB  - Single murine and human intestinal stem cells can be expanded in culture over
      long time periods as genetically and phenotypically stable epithelial organoids.
      Increased cAMP levels induce rapid swelling of such organoids by opening the
      cystic fibrosis transmembrane conductor receptor (CFTR). This response is lost in
      organoids derived from cystic fibrosis (CF) patients. Here we use the CRISPR/Cas9
      genome editing system to correct the CFTR locus by homologous recombination in
      cultured intestinal stem cells of CF patients. The corrected allele is expressed
      and fully functional as measured in clonally expanded organoids. This study
      provides proof of concept for gene correction by homologous recombination in
      primary adult stem cells derived from patients with a single-gene hereditary
      defect. 

PMID- 24315440
TI  - Correction of a genetic disease in mouse via use of CRISPR-Cas9.
AB  - The CRISPR-Cas9 system has been employed to generate mutant alleles in a range of
      different organisms. However, so far there have not been reports of use of this
      system for efficient correction of a genetic disease. Here we show that mice with
      a dominant mutation in Crygc gene that causes cataracts could be rescued by
      coinjection into zygotes of Cas9 mRNA and a single-guide RNA (sgRNA) targeting
      the mutant allele. Correction occurred via homology-directed repair (HDR) based
      on an exogenously supplied oligonucleotide or the endogenous WT allele, with only
      rare evidence of off-target modifications. The resulting mice were fertile and
      able to transmit the corrected allele to their progeny. Thus, our study provides
      proof of principle for use of the CRISPR-Cas9 system to correct genetic disease. 

PMID- 24315441
TI  - Induction of a human pluripotent state with distinct regulatory circuitry that
      resembles preimplantation epiblast.
AB  - Human embryonic stem cells (hESCs) are derived from the inner cell mass of the
      blastocyst. Despite sharing the common property of pluripotency, hESCs are
      notably distinct from epiblast cells of the preimplantation blastocyst. Here we
      use a combination of three small-molecule inhibitors to sustain hESCs in a LIF
      signaling-dependent hESC state (3iL hESCs) with elevated expression of NANOG and
      epiblast-enriched genes such as KLF4, DPPA3, and TBX3. Genome-wide transcriptome
      analysis confirms that the expression signature of 3iL hESCs shares similarities
      with native preimplantation epiblast cells. We also show that 3iL hESCs have a
      distinct epigenetic landscape, characterized by derepression of preimplantation
      epiblast genes. Using genome-wide binding profiles of NANOG and OCT4, we identify
      enhancers that contribute to rewiring of the regulatory circuitry. In summary,
      our study identifies a distinct hESC state with defined regulatory circuitry that
      will facilitate future analysis of human preimplantation embryogenesis and
      pluripotency.

PMID- 24315442
TI  - The THO complex regulates pluripotency gene mRNA export and controls embryonic
      stem cell self-renewal and somatic cell reprogramming.
AB  - Embryonic stem cell (ESC) self-renewal and differentiation are governed by a
      broad-ranging regulatory network. Although the transcriptional regulatory
      mechanisms involved have been investigated extensively, posttranscriptional
      regulation is still poorly understood. Here we describe a critical role of the
      THO complex in ESC self-renewal and differentiation. We show that THO
      preferentially interacts with pluripotency gene transcripts through Thoc5 and is
      required for self-renewal at least in part by regulating their export and
      expression. During differentiation, THO loses its interaction with those
      transcripts due to reduced Thoc5 expression, leading to decreased expression of
      pluripotency proteins that facilitates exit from self-renewal. THO is also
      important for the establishment of pluripotency, because its depletion inhibits
      somatic cell reprogramming and blastocyst development. Together, our data
      indicate that THO regulates pluripotency gene mRNA export to control ESC self
      renewal and differentiation, and therefore uncover a role for this aspect of
      posttranscriptional regulation in stem cell fate specification.

PMID- 24315444
TI  - Distinct functions for Wnt/beta-catenin in hair follicle stem cell proliferation
      and survival and interfollicular epidermal homeostasis.
AB  - Wnt/beta-catenin signaling is a central regulator of adult stem cells. Variable
      sensitivity of Wnt reporter transgenes, beta-catenin's dual roles in adhesion and
      signaling, and hair follicle degradation and inflammation resulting from broad
      deletion of epithelial beta-catenin have precluded clear understanding of
      Wnt/beta-catenin's functions in adult skin stem cells. By inducibly deleting beta
      catenin globally in skin epithelia, only in hair follicle stem cells, or only in
      interfollicular epidermis and comparing the phenotypes with those caused by
      ectopic expression of the Wnt/beta-catenin inhibitor Dkk1, we show that this
      pathway is necessary for hair follicle stem cell proliferation. However, beta
      catenin is not required within hair follicle stem cells for their maintenance,
      and follicles resume proliferating after ectopic Dkk1 has been removed,
      indicating persistence of functional progenitors. We further unexpectedly
      discovered a broader role for Wnt/beta-catenin signaling in contributing to
      progenitor cell proliferation in nonhairy epithelia and interfollicular epidermis
      under homeostatic, but not inflammatory, conditions. 

PMID- 24315445
TI  - Mononuclear anionic octahedral cobalt(III) complexes based on N-salicylidene-o
      aminophenol and its derivatives: synthetic, structural and spectroscopic studies.
AB  - The reactions of Co(II) sources with N-salicylidene-o-aminophenol (H2saph), N
      salicylidene-o-amino-4-methylphenol (H2saph-4Me) and N-salicylidene-o-amino-4
      chlorophenol (H2saph-4Cl) were studied in MeOH. The new solid complexes
      (Bu4(n)N)[Co(III)(saph)2] (1), (Et3NH)[Co(III)(saph-4Me)2]?MeOH?MeCO2H
      (2?MeOH?MeCO2H) and (Et3NH)[Co(III)(saph-4Cl)2]?MeOH?MeCO2H (3?MeOH?MeCO2H) have
      been isolated and their structures determined by single-crystal, X-ray
      crystallography. The three compounds contain the mononuclear, low- spin
      octahedral anion [Co(III)L2](-) (H2L=H2saph, H2saph-4Me, H2saph-4Cl), in which
      both L(2)(-) ligands act as tridentate chelating, meridional ONO donors. The
      crystal structures of 2?MeOH?MeCO2H and 3?MeOH?MeCO2H are built through H-bonding
      and pi-pi stacking interactions. The new complexes were characterized by
      elemental analyses and spectroscopic (IR, Raman, UV/VIS, (1)H NMR) data. All data
      are discussed in terms of the nature of bonding and known structures.

PMID- 24315443
TI  - Human iPSC-based modeling of late-onset disease via progerin-induced aging.
AB  - Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) resets
      their identity back to an embryonic age and, thus, presents a significant hurdle
      for modeling late-onset disorders. In this study, we describe a strategy for
      inducing aging-related features in human iPSC-derived lineages and apply it to
      the modeling of Parkinson's disease (PD). Our approach involves expression of
      progerin, a truncated form of lamin A associated with premature aging. We found
      that expression of progerin in iPSC-derived fibroblasts and neurons induces
      multiple aging-related markers and characteristics, including dopamine-specific
      phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived
      dopamine neurons revealed disease phenotypes that require both aging and genetic
      susceptibility, such as pronounced dendrite degeneration, progressive loss of
      tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body
      precursor inclusions. Thus, our study suggests that progerin-induced aging can be
      used to reveal late-onset age-related disease features in hiPSC-based disease
      models.

PMID- 24315446
TI  - Evaluation of the 3-dimensional, weight-bearing orientation of the normal adult
      knee.
AB  - The purpose of this study was to use 3-dimensional, weight-bearing images
      corrected for rotation to establish normative data of limb alignment and joint
      line orientation in asymptomatic, adult knees. One hundred adults (200 lower
      extremities) were recruited to receive weight-bearing, simultaneous biplanar
      imaging of both lower extremities. Multiple radiographic parameters were measured
      from 3D images, corrected for limb rotation. 70.0% of knees were in neutral,
      19.5% in varus, and 10.5% in valgus overall alignment. Only 31 % of knees
      possessed both a neutral mechanical axis and the absence of joint line obliquity.
      There was substantial agreement between the 2D and 3D images for overall
      mechanical alignment (kappa = 0.77), but only a moderate agreement for joint line
      obliquity (kappa = 0.58). A substantial portion of asymptomatic adults possess
      either a varus or valgus mechanical alignment and joint line obliquity.

PMID- 24315447
TI  - Uptake of environmental toxicants by the locus ceruleus: a potential trigger for
      neurodegenerative, demyelinating and psychiatric disorders.
AB  - BACKGROUND: Damage to the locus ceruleus, with a subsequent decrease of CNS
      noradrenaline, occurs in a wide range of neurodegenerative, demyelinating and
      psychiatric disorders. The cause of the initial locus ceruleus damage remains
      unknown. Recently, inorganic mercury was found to enter human locus ceruleus
      neurons selectively. This has led to the formulation of a new hypothesis as to
      the cause of these disorders. HYPOTHESIS: Toxicants enter locus ceruleus neurons
      selectively, aided by the extensive exposure these neurons have to CNS
      capillaries, as well as by stressors that upregulate locus ceruleus activity. The
      resulting noradrenaline dysfunction affects a wide range of CNS cells and can
      trigger a number of neurodegenerative (Alzheimer's, Parkinson's and motor neuron
      disease), demyelinating (multiple sclerosis), and psychiatric (major depression
      and bipolar disorder) conditions. CONCLUSIONS: This hypothesis proposes that
      environmental toxicants entering the locus ceruleus can give rise to a variety of
      CNS disorders. Proposals are made for experiments to gain further evidence for
      this hypothesis. If it is shown that toxicants in the locus ceruleus are
      responsible for these conditions, attempts can be made to prevent the toxicant
      exposures or to remove the toxicants from the nervous system.

PMID- 24315448
TI  - Studying the effects of smell and taste experience in the pediatric population
      using functional near infrared spectroscopy: a hypothesis.
AB  - There are different postnatal sensitive periods throughout the development course
      of sensory functions. During sensitive periods, there is a biological display of
      an extreme neural sensitivity to the storage of experience-driven sensory
      information that is not present outside these developmental stages. This neural
      property is reflected in subjects' reported preferences for sensory stimuli, such
      as odors and tastes. The human brain mapping approach (HBA) has demonstrated that
      disease-free human postnatal and later development of any sensory function
      parallels morphological and functional development of the CNS and that this
      development correlates with signal changes that have been acquired by means of
      neuroimaging techniques. Whether experience with tastes and/or odors has a
      stronger effect on the perception of gustatory and/or olfactory stimuli the
      earlier subjects are exposed to certain odors and tastes is still unknown. It is
      also unknown, whether as well as how this effect is reflected in brain activation
      patterns and whether we are currently able to identify sensitive periods of
      gustatory and olfactory development from the imaging signals. To answer these
      research questions, repeated exposure to tastes and/or odors should be applied in
      children of different age ranges in order to induce different age-related degrees
      of olfactory/gustatory preferences as well as different aged-related patterns of
      oxyhemoglobin (OH) and deoxyhemoglobin (DOH) changes that should be measured by
      means of the functional near-infrared spectroscopy (fNIRS) technique. 

PMID- 24315449
TI  - Allergen microarray detects high prevalence of asymptomatic IgE sensitizations to
      tropical pollen-derived carbohydrates.

PMID- 24315452
TI  - Celiac artery compression: EUS evaluation.

PMID- 24315450
TI  - Novel childhood asthma genes interact with in utero and early-life tobacco smoke
      exposure.

PMID- 24315453
TI  - Gastrodiscoides hominis infestation of colon: endoscopic appearance.

PMID- 24315454
TI  - A comparative evaluation of outcomes of endoscopic versus percutaneous drainage
      for symptomatic pancreatic pseudocysts.
AB  - BACKGROUND: Endoscopic drainage (ED) and percutaneous drainage (PD) have largely
      replaced surgical drainage as the initial approach for symptomatic pseudocysts.
      However, there are few studies comparing ED and PD. OBJECTIVE: To compare the
      outcomes of ED and PD for symptomatic pseudocysts. DESIGN: Retrospective cohort
      study. SETTING: Academic center. PATIENTS: Adult patients with symptomatic
      pseudocysts within <= 1 cm of the gastric or duodenal wall who underwent ED or PD
      between 1993 and 2011. Patients with walled-off pancreatic necrosis were
      excluded. INTERVENTION: ED or PD. MAIN OUTCOME MEASUREMENTS: Rates of technical
      success, procedural adverse events, clinical success, reinterventions, and
      failure. Other outcomes included the length of hospital stay and number of follow
      up abdominal imaging studies. RESULTS: There were 81 patients, 41 who underwent
      ED and 40 who underwent PD, with no differences in age, sex, and comorbidity
      between the 2 groups. There were no differences in the rates of technical success
      (90.2% vs 97.5%; P = .36), adverse events (14.6% vs 15%; P = .96), and clinical
      success (70.7% vs 72.5%; P = .86) between ED and PD, respectively. Patients who
      underwent PD had higher rates of reintervention (42.5% vs 9.8%; P = .001), longer
      length of hospital stay (14.8 +/- 14.4 vs 6.5 +/- 6.7 days; P = .001), and median
      number [quartiles] of follow-up abdominal imaging studies (6 [3.25, 10] vs 4
      [2.5, 6]; P = .02) compared with patients who underwent ED. LIMITATIONS: Single
      center, retrospective study. CONCLUSION: ED and PD have similar clinical success
      rates for symptomatic pseudocysts. However, PD is associated with significantly
      higher rates of reintervention, longer length of hospital stay, and increased
      number of follow-up abdominal imaging studies.

PMID- 24315451
TI  - Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2
      q12 and 17q12-q21 variants.
AB  - BACKGROUND: The fraction of exhaled nitric oxide (Feno) value is a biomarker of
      eosinophilic airway inflammation and is associated with childhood asthma.
      Identification of common genetic variants associated with childhood Feno values
      might help to define biological mechanisms related to specific asthma phenotypes.
      OBJECTIVE: We sought to identify the genetic variants associated with childhood
      Feno values and their relation with asthma. METHODS: Feno values were measured in
      children age 5 to 15 years. In 14 genome-wide association studies (N = 8,858), we
      examined the associations of approximately 2.5 million single nucleotide
      polymorphisms (SNPs) with Feno values. Subsequently, we assessed whether
      significant SNPs were expression quantitative trait loci in genome-wide
      expression data sets of lymphoblastoid cell lines (n = 1,830) and were related to
      asthma in a previously published genome-wide association data set (cases, n =
      10,365; control subjects: n = 16,110). RESULTS: We identified 3 SNPs associated
      with Feno values: rs3751972 in LYR motif containing 9 (LYRM9; P = 1.97 * 10(-10))
      and rs944722 in inducible nitric oxide synthase 2 (NOS2; P = 1.28 * 10(-9)), both
      of which are located at 17q11.2-q12, and rs8069176 near gasdermin B (GSDMB; P =
      1.88 * 10(-8)) at 17q12-q21. We found a cis expression quantitative trait locus
      for the transcript soluble galactoside-binding lectin 9 (LGALS9) that is in
      linkage disequilibrium with rs944722. rs8069176 was associated with GSDMB and
      ORM1-like 3 (ORMDL3) expression. rs8069176 at 17q12-q21, but not rs3751972 and
      rs944722 at 17q11.2-q12, were associated with physician-diagnosed asthma.
      CONCLUSION: This study identified 3 variants associated with Feno values,
      explaining 0.95% of the variance. Identification of functional SNPs and
      haplotypes in these regions might provide novel insight into the regulation of
      Feno values. This study highlights that both shared and distinct genetic factors
      affect Feno values and childhood asthma.

PMID- 24315455
TI  - Hitting a moving target: targeting transient protein states.
AB  - In this issue of Structure, Bista and colleagues report that inhibitors of the
      MDM2/p53 interaction can be designed to interact with a transiently folded alpha
      helical segment of the MDM2 lid region. This suggests that targeting transient
      protein states in PPI inhibitor design could be a promising strategy to improve
      affinity and/or selectivity profiles. 

PMID- 24315456
TI  - Secrets of a secretin.
AB  - Secretins are major constituents of bacterial type III secretion systems (T3SS).
      In this issue of Structure, Kowal and colleagues report on the cryo-EM structure
      of the native YscC secretin from Yersinia, revealing its internal symmetry and
      mode of length adaptation. 

PMID- 24315458
TI  - Eppur si muove! The 2013 Nobel Prize in Chemistry.
AB  - The 2013 Nobel Prize in Chemistry has been awarded to Martin Karplus, Michael
      Levitt, and Arieh Warshel for their work on developing computational methods to
      study complex chemical systems. Their work has led to mechanistic critical
      insights into chemical systems both large and small and has enabled progress in a
      number of different fields, including structural biology.

PMID- 24315457
TI  - Refining a Jagged edge.
AB  - In a recent Cell Reports article, Chillakuri and colleagues showed that the N
      terminal "MNNL" domain of the essential Notch ligand Jagged1 resembles a C2
      domain and relies on calcium binding to facilitate productive signal
      transduction. 

PMID- 24315459
TI  - In vitro and in vivo correlation of paclitaxel-loaded polymeric microparticles.

PMID- 24315460
TI  - Diabetes in the Africa Region: an update.
AB  - The Africa Region (AFR), where diabetes was once rare, has witnessed a surge in
      the condition. Estimates for type 1 diabetes suggest that about 39,000 people
      suffer from the disease in 2013 with 6.4 new cases occurring per year per 100,000
      people in children <14 years old. Type 2 diabetes prevalence among 20-79-year
      olds is 4.9% with the majority of people with diabetes <60 years old; the highest
      proportion (43.2%) is in those aged 40-59 years. Figures are projected to
      increase with the numbers rising from 19.8 million in 2013 to 41.5 million in
      2035, representing a 110% absolute increase. There is an apparent increase in
      diabetes prevalence with economic development in AFR with rates of 4.4% in low
      income, 5.0% in lower-middle income and 7.0% in upper-middle income countries. In
      addition to development and increases in life-expectancy, the likely progression
      of people at high risk for the development of type 2 diabetes will drive the
      expected rise of the disease. This includes those with impaired glucose
      tolerance, the prevalence of which is 7.3% among 20-79-year-olds in 2013.
      Mortality attributable to diabetes in 2013 in AFR is expected to be over half a
      million with three-quarter of these deaths occurring in those <60 years old. The
      prevalence of undiagnosed diabetes remains unacceptably high at 50.7% and is much
      higher in low income (75.1%) compared to lower- and upper-middle income AFR
      countries (46.0%). This highlights the inadequate response of local health
      systems which need to provide accessible, affordable and optimal care for
      diabetes. 

PMID- 24315461
TI  - Treatment with angiotensin II receptor blockers is associated with prolonged
      relapse-free survival, lower relapse rate, and corticosteroid-sparing effect in
      patients with giant cell arteritis.
AB  - OBJECTIVE: To determine whether concomitant treatment with angiotensin-converting
      enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is associated
      with changes in the outcome of patients with giant cell arteritis (GCA). METHODS:
      A study cohort of 106 patients with biopsy-proven GCA was longitudinally followed
      up for 7.8 +/- 3.3 years. Patients were stratified according to their treatment
      with ACEI, ARB, or no ACEI/ARB. Time to first relapse, number of flares, time to
      achieve a stable prednisone dose <10mg/day and <5mg/day with no relapses, time
      required to completely discontinue prednisone, cumulative dose of prednisone
      received during the first year, and concentrations of acute-phase reactants at
      pre-defined time points (baseline, 6, 12, 18, and 24 months) were compared among
      the 3 groups. Cox proportional hazards models were performed to adjust for
      potential confounders. RESULTS: Patients receiving ARB presented a significantly
      longer relapse-free survival than patients treated with ACEI or patients not
      receiving ACEI/ARB (p = 0.02). The adjusted hazard ratio for relapses in patients
      treated with ARB was 0.32 (95% CI: 0.12-0.81, p = 0.017). In addition, patients
      who received ARB achieved a prednisone maintenance dose <10mg/day faster than all
      other patients (p = 0.0002). No significant differences were observed among
      groups in acute-phase reactant levels during follow-up. However, patients not
      receiving ACEI/ARB had significantly higher C-reactive protein and haptoglobin
      concentrations than those receiving ACEI or ARB at various time points.
      CONCLUSIONS: Addition of ARB to glucocorticoids is associated with lower relapse
      rate and more prolonged disease-free survival in patients with GCA.

PMID- 24315462
TI  - Task-specific performance effects with different numeric keypad layouts.
AB  - Two commonly used keypad arrangements are the telephone and calculator layouts.
      The purpose of this study was to determine if entering different types of numeric
      information was quicker and more accurate with the telephone or the calculator
      layout on a computer keyboard numeric keypad. Fifty-seven participants saw a 10
      digit numeric stimulus to type with a computer number keypad as quickly and as
      accurately as possible. Stimuli were presented in either a numerical
      [1,234,567,890] or phone [(123) 456-7890] format. The results indicated that
      participants' memory of the layout for the arrangement of keys on a telephone was
      significantly better than the layout of a calculator. In addition, the results
      showed that participants were more accurate when entering stimuli using the
      calculator keypad layout. Critically, participants' response times showed an
      interaction of stimulus format and keypad layout: participants were specifically
      slowed when entering numeric stimuli using a telephone keypad layout. Responses
      made using the middle row of keys were faster and more accurate than responses
      using the top and bottom row of keys. Implications for keypad design and cell
      phone usage are discussed. 

PMID- 24315463
TI  - Matching performance of vehicle icons in graphical and textual formats.
AB  - The current research classified 82 vehicle icons into seven categories (image
      related, concept-related, semi-abstract, arbitrary, abbreviation, word, and
      combined) for their matching accuracy, matching sequence, and matching time.
      These data can be compared and used as a framework for future icon development.
      Forty participants, all with a university degree, took part in this experiment.
      Half of the participants had intensive driving experience, while the other half
      never driven a car. The results indicated that on average, word icons had a
      significantly greater matching accuracy than the other icon formats; ranging from
      4.7 to 20.8% difference. Regarding the matching sequence, participants matched
      image-related icons before other icon formats. Arbitrary and combined icons took
      significantly longer to match than other icon formats by 1.4-6.2 s. Based on the
      high matching accuracy (86.3%) and high ratings on subjective design features,
      word format can be used for functions describable using simple English for users
      with English reading ability. Confusion matrices showed that 63.2% of the
      misunderstandings were caused by similarity in format or function.

PMID- 24315464
TI  - Rituximab in the treatment of shrinking lung syndrome in systemic lupus
      erythematosus.
AB  - Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus
      erythematosus. We report the case of a patient with non-responding SLS (neither
      to glucocorticoids nor immunosupresors), who showed remarkable improvement after
      the onset of treatment with rituximab. Although there is a little evidence,
      treatment with rituximab could be proposed in SLS when classical treatment fails.

PMID- 24315465
TI  - Nodular regenerative hyperplasia of the liver as a complication of long-standing
      systemic-onset juvenile idiopathic arthritis.

PMID- 24315466
TI  - Contaminant removal.

PMID- 24315467
TI  - Designing trials of behavioral interventions to increase physical activity in
      patients with COPD: insights from the chronic disease literature.
AB  - OBJECTIVES: There is increasing evidence that physical activity (PA) can affect
      health outcomes, particularly in chronic disease. While pharmacologic therapy and
      exercise training can improve exercise capacity, increasing PA requires behavior
      change. This review examined clinical trials testing the effectiveness of
      behavioral interventions to increase PA in adults with chronic disease to inform
      future research in COPD. METHODS: Embase and PubMed searches of studies published
      in English, 1995-2011. INCLUSION CRITERIA: Adults >= 45 years; COPD, diabetes,
      heart failure, obesity; exercise or PA endpoint; behavioral intervention
      described in sufficient detail to permit interpretation. RESULTS: 932 abstracts
      screened; 169 articles retrieved; 36 reviewed. Most were randomized trials (n =
      32, 89%); 2 arms (n = 26, 72%), sample sizes 40-100 (n = 15, 42%); recruitment
      through clinical settings (n = 28, 78%); disease severity as primary eligibility
      criterion (n = 23, 64%); mean duration: 10 months (range: 1-84). Exercise
      intervention: aerobic activity, 30-60 min (n = 20, 56%), 3-5 times/week (n = 20,
      56%). Behavioral intervention: Counseling (n = 19, 53%) with personal follow-up
      (n = 12, 33%). CONTROL GROUP: Exercise without behavioral intervention (n = 14,
      39%) or usual care (n = 15, 42%). Significant effects were reported in 15 of 25
      (60%) studies testing exercise capacity (6-minute walk, cycle, treadmill), 19 of
      26 (73%) testing PA (pedometer, activity log, questionnaire), 11 of 22 (50%)
      measuring quality of life, and 8 of 13 (62%) capturing behavioral endpoints.
      CONCLUSIONS: This review provides insight into the range of designs,
      interventions, and outcome measures used in studies testing methods to improve PA
      in chronic disease with implications for designing trials in COPD.

PMID- 24315468
TI  - Eligibility for treatment with omalizumab in Italy and Germany.
AB  - Omalizumab is an add-on therapy for patients with uncontrolled severe allergic
      asthma. In Europe, patients must fulfil a number of additional criteria to become
      eligible for omalizumab therapy, creating a challenge for epidemiology studies to
      quantify the potential patient pool. Thus, and in the absence of robust data, the
      number of omalizumab-eligible patients has remained unclear. To assess eligible
      patient numbers, a chart-audit design approach was employed to measure
      epidemiology variables based on patient-level data. 770 patient charts were
      reviewed in designated towns in Germany and Italy, in collaboration with >200
      primary care physicians (PCPs) and respiratory specialists (RS). This study
      sample represents >50% and >70% of local RS in these designated towns of Germany
      and Italy, respectively. Of patient charts evaluated, 4 patients were currently
      receiving omalizumab. A further 31 patients (12 PCP; 19 RS) were evaluated as
      omalizumab-eligible (i.e. fulfilled all product label criteria) but were not
      receiving the drug. Extrapolating to a national level, this yields >6500 eligible
      patients in Germany, and >3200 in Italy. Furthermore, this study sample revealed
      a significant number of PCPs treating uncontrolled severe asthma patients without
      referral to RS; these patients are not consistently evaluated for FEV1, aero
      allergen sensitivity, a qualitative understanding of severe exacerbations, and
      day and night-time symptoms. This study suggests that significant numbers of
      omalizumab-naive severe allergic asthma patients in Germany/Italy are eligible
      for omalizumab therapy. Despite proven benefits in uncontrolled severe allergic
      asthma, adjunctive omalizumab therapy is underutilized. 

PMID- 24315469
TI  - Systematic review of non-invasive positive pressure ventilation for chronic
      respiratory failure.
AB  - BACKGROUND: This systematic review examined the effect of non-invasive positive
      pressure ventilation (NIPPV) on patient reported outcomes (PROs) and survival for
      individuals with or at risk of chronic respiratory failure (CRF). METHODS:
      Randomised controlled trials (RCTs) and prospective non-randomised studies in
      those treated with NIPPV for CRF were identified from electronic databases,
      reference lists and grey literature. Diagnostic groups included in the review
      were amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), Duchenne
      muscular dystrophy (DMD), restrictive thoracic disease (RTD) and obesity
      hypoventilation syndrome (OHS). RESULTS: Eighteen studies were included and
      overall study quality was weak. Those with ALS/MND had improved somnolence and
      fatigue as well as prolonged survival with NIPPV. For OHS, improvements in
      somnolence and fatigue, dyspnoea and sleep quality were demonstrated, while for
      RTD, measures of dyspnoea, sleep quality, physical function and health, mental
      and emotional health and social function improved. There was insufficient
      evidence to form conclusions regarding the effect of NIPPV for those with DMD.
      CONCLUSIONS: This review has demonstrated that NIPPV influences PROs differently
      depending on the underlying cause of CRF. These findings may provide assistance
      to patients and clinicians to determine the relative costs and benefits of NIPPV
      therapy and also highlight areas in need of further research.

PMID- 24315470
TI  - Prognostic value of bronchial provocation and FENO measurement for asthma
      diagnosis--results of a delayed type of diagnostic study.
AB  - OBJECTIVES: To compare the prognostic value of FENO with bronchoprovocation
      testing when the clinical course within the first year after assessment was taken
      into account; to compare the prognostic values with respect to eosinophilic
      versus non-eosinophilic inflammatory pattern. METHODS: Cross-sectional diagnostic
      study with a delayed-type reference standard in 393 patients attending a private
      practice of pneumologists with complaints suspicious of obstructive airway
      disease. INDEX TEST: FENO measurement. Reference standard: ratio FEV1/VC or
      airway resistance assessed by body plethysmography, with additional
      bronchoprovocation or bronchodilator testing, as well as spontaneous sputum
      (smear slides). This was combined with a follow-up evaluation by a structured
      interview after 12 months. RESULTS: 302 (76.8%) patients were reached for follow
      up. Regarding asthma diagnosis, the area under the curve (AUC) for FENO was 0.603
      (95%CI 0.528-0.677) for the whole group. With eosinophilic asthma as target, AUC
      increased (0.819 (95%CI 0.703-0.934)) and exceeded that of bronchoprovocation
      (0.711 (95%CI 0.584-0.874)). FENO showed no diagnostic value in non-eosinophilic
      asthma. In patients reporting wheezing and allergic rhinitis at the initial
      assessment, its positive predictive value was 90.9% (95%CI 62.3%-98.4) at a cut
      off of 45 ppb, and 100% (95%CI 56.6-100%) at 81 ppb. CONCLUSIONS: FENO bears
      limited information when measured non-specifically in primary care, but is useful
      for diagnosing eosinophilic asthma. If sputum is not available, information on
      wheezing and rhinitis can narrow down the range of patients in whom FENO is
      informative. Moreover, the evaluation of the clinical value of FENO benefits from
      taking into account follow-up data to confirm the diagnosis.

PMID- 24315471
TI  - Computational proteomics, systems biology and clinical implications.

PMID- 24315472
TI  - [Reassurance: an essential but difficult medical task with neglected social and
      economic outcomes].

PMID- 24315473
TI  - [Complicated course of eosinophilic gastroenteritis: a case report and literature
      review].
AB  - INTRODUCTION: Eosinophilic gastroenteritis is an unusual disease characterized by
      an eosinophilic infiltration of the gastrointestinal tract. The esophageal
      location of this disorder is uncommon and is usually revealed by dysphagia.
      Diagnosis is obtained by histology during endoscopy after exclusion of
      differential diagnosis. Treatment is based on systemic corticosteroids, which
      improve dramatically symptoms and endoscopic lesions. CASE REPORT: We report an
      88-year-old man who presented eosinophilic gastroenteritis with esophageal injury
      complicated by gastrointestinal haemorrhage and fistule. CONCLUSION: Eosinophilic
      gastroenteritis may have a potentially unfavourable outcome. The treatment of
      complicated forms is not codified and often empirical.

PMID- 24315474
TI  - [A facial pigmentation].

PMID- 24315475
TI  - Radiation and contrast agent doses reductions by using 80-kV tube voltage in
      coronary computed tomographic angiography: a comparative study.
AB  - OBJECTIVE: To investigate the effects of 80-kilovoltage (kV) tube voltage
      coronary computed tomographic angiography (CCTA) with a reduced amount of
      contrast agent on qualitative and quantitative image quality parameters and on
      radiation dose in patients with a body mass index (BMI) <23.0 kg/m(2). METHODS:
      One hundred and twenty consecutive patients with a BMI <23.0 kg/m(2) and a low
      calcium load undergoing retrospective electrocardiogram (ECG)-gated dual-source
      CCTA were randomized into two groups [standard-tube voltage (120-kV) vs. low-tube
      voltage (80-kV)]. The injection flow rate of contrast agent (350 mg I/mL) was
      adjusted to body weight of each patient (4.5-5.5 mL/s in the 120-kV group and 2.8
      3.8 mL/s in the 80-kV group). Radiation and contrast agent doses were evaluated.
      Quantitative image quality parameters and figure of merit (FOM) of coronary
      artery were evaluated. Each coronary segment was evaluated for image quality on a
      4-point scale. RESULTS: Compared with the 120-kV group, effective dose and amount
      of contrast agent in the 80-kV group were decreased by 57.8% and 30.5% (effective
      dose:2.7 +/- 0.5 vs. 6.4 +/- 1.3 mSv; amount of contrast agent:57.1 +/- 3.2 vs.
      82.1 +/- 6.1 mL; both p<0.0001), respectively. Image noise was 22.7 +/- 2.1HU for
      120-kV images and 33.2 +/- 5.2 HU for 80-kV images (p<0.0001). Signal-to-noise
      ratio (SNR) and contrast-to-noise ratio (CNR) in the proximal right coronary
      artery (RCA) and left main coronary artery (LMA) were all lower in 80-kV than 120
      kV images (SNR in the proximal RCA: 16.5 +/- 1.8 vs. 19.4 +/- 2.8; SNR in the
      LMA: 16.3 +/- 2.0 vs.19.6 +/- 2.7; CNR in the proximal RCA: 19.4 +/- 2.3 vs.22.9
      +/- 3.0; CNR in the LMA: 18.8 +/- 2.4 vs. 22.7 +/- 2.9; all p<0.0001). FOM were
      all significantly higher in 80-kV than 120-kV images (proximal RCA: 146.7 +/-
      45.1 vs. 93.4 +/- 32.0; LMA: 139.1 +/- 47.2 vs. 91.6 +/- 31.1; all p<0.0001).
      There was no significant difference in image quality score between the two groups
      (3.3 +/- 0.8 vs. 3.3 +/- 0.8, p=0.068) despite decreased SNR and CNR of coronary
      artery in the 80-kV group. CONCLUSION: The 80-kV protocol significantly reduces
      radiation and contrast agent doses in CCTA in patients with a low BMI <23.0
      kg/m(2) and a low calcium load while maintaining image quality.

PMID- 24315476
TI  - The influence of partial subscapularis tendon tears combined with supraspinatus
      tendon tears.
AB  - BACKGROUND: With the advent of arthroscopy, more partial subscapularis tears are
      being recognized. The biomechanical effects of partial subscapularis tears are
      unknown, and there is no consensus as to their treatment. Therefore, the
      objective of this study was to evaluate and to quantify the changes in range of
      motion and glenohumeral kinematics for isolated subscapularis partial tears,
      combined subscapularis and supraspinatus tears, supraspinatus repair, and
      combined supraspinatus and subscapularis repair. METHODS: Six cadaveric shoulders
      were tested in the scapular plane with 0 degrees , 30 degrees , and 60 degrees 
      shoulder abduction under 6 conditions: intact; 1/4 subscapularis tear; 1/2
      subscapularis tear; 1/2 subscapularis and complete supraspinatus tear;
      supraspinatus repair; and supraspinatus and subscapularis repair. Maximum
      internal and external rotation and glenohumeral kinematics were measured under
      physiologic muscle loading condition. A repeated measures analysis of variance
      with a Tukey post hoc test was used for statistical analysis. RESULTS: Maximum
      external rotation was significantly increased after 1/4 subscapularis tear at 30
      degrees  abduction and in all abduction angles with 1/2 subscapularis tear (P <
      .05). The 2 repair conditions did not restore external rotation to the intact
      level. At maximum internal and external rotation, there was a significant
      superior shift in the humeral head apex position with 1/4 subscapularis tear at
      30 degrees  abduction and with 1/2 subscapularis tear at 60 degrees  abduction (P
      < .05). Repair of the supraspinatus tendon partially corrected abnormal
      kinematics; however, neither repair restored abnormal kinematics to intact.
      CONCLUSION: Additional repair of the partial subscapularis tear with
      supraspinatus tear did not affect external rotation or glenohumeral kinematics.
      Further studies are needed to evaluate different subscapularis repair techniques.
      LEVEL OF EVIDENCE: Basic science study, biomechanics.

PMID- 24315478
TI  - Evaluating an online pharmaceutical education system for pharmacy interns in
      critical care settings.
AB  - Incorporating electronic learning (eLearning) system into professional
      experimental programs such as pharmacy internships is a challenge. However, none
      of the current systems can fully support the unique needs of clinical pharmacy
      internship. In this study we enhanced a commercial eLearning system for clinical
      pharmacy internship (The Clinical Pharmacy Internship eLearning System, CPIES).
      The KAP questionnaire was used to evaluate the performance of group A with the
      traditional teaching model and group B with the CPIES teaching model. The CPIES
      teaching model showed significant improvement in interns' knowledge and practice
      (p = 0.002 and 0.031, respectively). The traditional teaching model only
      demonstrated significant improvement in practice (p = 0.011). Moreover,
      professionalism, such as attitudes on cooperating with other health
      professionals, is developed by learning from a good mentor. The on-line teaching
      and traditional teaching methods should undoubtedly be blended in a complete
      teaching model in order to improve learners' professional knowledge, facilitate
      correct attitude, and influence good practice.

PMID- 24315477
TI  - Shoulder arthroplasty for rheumatoid arthritis: 303 consecutive cases with
      minimum 5-year follow-up.
AB  - BACKGROUND: This is an update on a previously documented cohort of patients who
      underwent shoulder arthroplasty for rheumatoid arthritis, with a minimum 5-year
      clinical follow-up. METHODS: The survivorship of 303 consecutive shoulder
      arthroplasties (108 hemiarthroplasties, 195 total shoulder arthroplasties) for
      rheumatoid arthritis at one institution was assessed. There were 255
      arthroplasties in the clinical analysis and 188 in the radiographic analysis.
      RESULTS: Kaplan-Meier survivorship free of revision at 5 years and 10 years was
      96.1% and 92.9% for total shoulder arthroplasty (TSA) and 89.2% and 87.9% for
      hemiarthroplasty (HA). The most common indications were glenoid loosening (5%)
      and infection (2%) for TSA revision and glenoid arthrosis (7%) for HA revision.
      Pain relief was greater with TSA than with HA. In patients with an intact rotator
      cuff, in comparing TSA with HA, those with a TSA had greater improvements in pain
      scores (-2.7 vs. -1.8 on a 5-point scale) and degrees of elevation (45 versus 24)
      (P = .08). Approximately 30% of humeral components and 73% of glenoid components
      had periprosthetic lucencies. There was a shift in position of the glenoid in 33%
      of TSAs, and 36% were "at risk." Eighty-one percent of HAs had moderate or severe
      glenoid erosion. DISCUSSION/CONCLUSION: Both HA and TSA provide pain relief and
      improved motion in patients with rheumatoid arthritis. In patients with an intact
      rotator cuff, pain relief and range of motion are more improved with TSA compared
      with HA. There is a high rate of component lucency, but component revision is
      uncommon. LEVEL OF EVIDENCE: Level IV, case series, treatment study.

PMID- 24315479
TI  - Upper gastrointestinal tract metastasis from lung cancer.

PMID- 24315480
TI  - Herbal hepatotoxicity: analysis of cases with initially reported positive re
      exposure tests.
AB  - BACKGROUND: Positive re-exposure tests are diagnostic hallmarks for
      hepatotoxicity. OBJECTIVE: To test validity of positive re-exposures in herb
      induced liver injury. METHODS: We searched Medline database for cases of herb
      induced liver injury with positive re-exposures and analysed 34 cases for
      positive re-exposure test criteria of baseline alanine aminotransferase< 5N
      before re-exposure, and re-exposure alanine aminotransferase >= 2* baseline
      alanine aminotransferase. Re-exposure test was negative, if baseline alanine
      aminotransferase< 5N combined with re-exposure alanine aminotransferase< 2*
      baseline alanine aminotransferase, or if baseline alanine aminotransferase>= 5N
      regardless of the re-exposure alanine aminotransferase including no available re
      exposure alanine aminotransferase result. RESULTS: In 21/34 cases (61.8%),
      criteria for a positive re-exposure were fulfilled, with negative tests in 6/34
      cases (17.6%) or uninterpretable ones in 7/34 cases (20.6%). Confirmed positive
      re-exposure tests established potential of herb induced liver injury for Aloe,
      Chaparral, Chinese herbal mixtures, Chinese Jin Bu Huan, Chinese Syo Saiko To,
      Germander, Greater Celandine, Green tea, Kava, Mistletoe, Polygonum multiflorum,
      and Senna, with up to 4 case reports per herb. CONCLUSIONS: Among 34 cases of
      herb-induced liver injury with initially reported positive re-exposure tests,
      61.8% of the cases actually fulfilled established test criteria and provided firm
      diagnoses of herb induced liver injury by various herbs.

PMID- 24315481
TI  - Bio-based products from solar energy and carbon dioxide.
AB  - Producing bio-based products directly from CO2 and solar energy is a desirable
      alternative to the conventional biorefining that relies on biomass feedstocks.
      The production paradigm is based on an artificial photosynthetic system that
      converts sunlight to electricity and H2 via water electrolysis. An autotrophic H2
      oxidizing bacterium fixes CO2 in dark conditions. The assimilated CO2 is stored
      in bacterial cells as polyhydroxybutyrate (PHB), from which a range of products
      can be derived. Compared with natural photosynthesis of a fast-growing
      cyanobacterium, the artificial photosynthetic system has much higher energy
      efficiency and productivity of bio-based products. The new technology looks
      promising because of possible cost reduction in feedstock, equipment, and
      operation.

PMID- 24315482
TI  - Direct and reversed dorsal digito-metacarpal flaps: a review of 24 cases.
AB  - BACKGROUND AND AIM: The common source for reconstruction of soft tissue defects
      of the fingers is either the same finger or the adjacent finger. However, when
      the donor areas are damaged by concomitant injuries, these options are not
      available. The purpose of this study was to report on reconstruction of these
      complex digital injuries using the dorsal digito-metacarpal flaps (DDMFs) and to
      evaluate the efficacy of this technique. METHODS: A retrospective study was
      conducted with 24 patients who had their fingers reconstructed using the DDMF
      from April 2009 to September 2011. The patients were divided into two groups
      based on the flow direction of the blood supply. Among them, nine patients had
      their fingers reconstructed with the direct DDMFs. Fifteen patients underwent
      tissue reconstruction in the distal phalanx with the reversed DDMFs. RESULTS: At
      a mean follow-up of 20 months (range, 18-24 months), the mean static two-point
      discrimination on the flaps was 8.3 mm (range, 7-10 mm) in the direct DDMF group
      and 10.4 mm (range, 9-14 mm) in the reversed DDMF group, with a significant
      difference (P=0.001). The range of motion of the donor fingers was similar to
      that of the opposite hands. According to the Michigan Hand Outcomes
      Questionnaire, 11 patients were very satisfied, 10 were satisfied and three were
      neither satisfied nor dissatisfied with functional recovery of the reconstructed
      finger. CONCLUSIONS: The DDMF is an additional option for coverage of a soft
      tissue defect of the finger when the commonly used local and regional flaps are
      not feasible. CLINICALTRIALSGOV ID: NCT 01927003. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic/IV.

PMID- 24315483
TI  - Fat embolism following pelvic injuries: a subclinical event or an increased risk
      of mortality?

PMID- 24315485
TI  - Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation.
AB  - TET proteins oxidize 5-methylcytosine (5mC) on DNA and play important roles in
      various biological processes. Mutations of TET2 are frequently observed in
      myeloid malignance. Here, we present the crystal structure of human TET2 bound to
      methylated DNA at 2.02 A resolution. The structure shows that two zinc fingers
      bring the Cys-rich and DSBH domains together to form a compact catalytic domain.
      The Cys-rich domain stabilizes the DNA above the DSBH core. TET2 specifically
      recognizes CpG dinucleotide and shows substrate preference for 5mC in a CpG
      context. 5mC is inserted into the catalytic cavity with the methyl group
      orientated to catalytic Fe(II) for reaction. The methyl group is not involved in
      TET2-DNA contacts so that the catalytic cavity allows TET2 to accommodate 5mC
      derivatives for further oxidation. Mutations of Fe(II)/NOG-chelating, DNA
      interacting, and zinc-chelating residues are frequently observed in human
      cancers. Our studies provide a structural basis for understanding the mechanisms
      of TET-mediated 5mC oxidation. 

PMID- 24315484
TI  - Microbiota modulate behavioral and physiological abnormalities associated with
      neurodevelopmental disorders.
AB  - Neurodevelopmental disorders, including autism spectrum disorder (ASD), are
      defined by core behavioral impairments; however, subsets of individuals display a
      spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier
      defects and microbiota alterations in the maternal immune activation (MIA) mouse
      model that is known to display features of ASD. Oral treatment of MIA offspring
      with the human commensal Bacteroides fragilis corrects gut permeability, alters
      microbial composition, and ameliorates defects in communicative, stereotypic,
      anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum
      metabolomic profile, and B. fragilis modulates levels of several metabolites.
      Treating naive mice with a metabolite that is increased by MIA and restored by B.
      fragilis causes certain behavioral abnormalities, suggesting that gut bacterial
      effects on the host metabolome impact behavior. Taken together, these findings
      support a gut-microbiome-brain connection in a mouse model of ASD and identify a
      potential probiotic therapy for GI and particular behavioral symptoms in human
      neurodevelopmental disorders.

PMID- 24315486
TI  - Efficacy and safety of concurrent collagenase clostridium histolyticum injections
      for multiple Dupuytren contractures.
AB  - PURPOSE: To assess the safety and efficacy of 2 concurrent injections of
      collagenase clostridium histolyticum (CCH) in the same hand to treat multiple
      Dupuytren flexion contractures. METHODS: In a multicenter, open-label phase IIIb
      study, 60 patients received two 0.58-mg CCH doses injected into cords affecting 2
      joints in the same hand during 1 visit, followed by finger extension
      approximately 24 hours later. Efficacy at postinjection day 30 (change in flexion
      contracture and active range of motion, patient satisfaction, physician-rated
      improvement, and rates of clinical success [flexion contracture 5 degrees  or
      less]) and adverse events were summarized. RESULTS: The concurrent injections
      were most commonly administered in cords affecting metacarpophalangeal (MCP) and
      proximal interphalangeal (PIP) joints on the same finger (47%) or 2 MCP joints on
      different fingers of the same hand (37%). Mean total (sum of the 2 treated
      joints) flexion contracture decreased 76%, from 87 degrees  to 24 degrees  (MCP
      joints: 86%; PIP joints: 66%). Mean total range of motion increased from 100
      degrees  to 161 degrees . Clinical success was 76% for MCP joints and 33% for PIP
      joints. Most patients were very satisfied (60%) or quite satisfied (28%) with
      treatment. Most investigators rated treated joints as very much improved (55%) or
      much improved (37%). The most common treatment-related adverse events (> 75% of
      patients) were contusion, pain in extremity, and edema peripheral (local edema).
      Most adverse events were mild to moderate in severity. Serious complications
      included 1 pulley rupture related to study medication and 1 flexor tendon rupture
      (following conclusion of the study). There were no systemic complications.
      CONCLUSIONS: Results suggest that 2 affected joints can be effectively and safely
      treated with concurrent CCH injections. There was an increased incidence of some
      adverse events with concurrent treatment (pruritus, lymphadenopathy, blood
      blister, and skin laceration) compared with treatment of a single joint. High
      degrees of patient satisfaction and physician-rated improvement were reported.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24315487
TI  - How to establish an interactive eConference and eJournal Club.
AB  - With our hand team scattered across several different locations, it is difficult
      to find a time to get together for our weekly didactic hand conference and
      monthly hand journal club. In addition, traffic and tight clinical schedules
      sometimes force conferences to start late or be canceled. Our solution was to set
      up an on-line conference. Using TeamViewer to host our conference and Skype to
      host our journal clubs, we experienced increased attendance by both faculty and
      residents in our meetings. In this article, we establish a method of hosting
      effective on-line videoconferences to facilitate nearly universal participation
      of our hand team, and we hope to assist others who wish to establish similar
      setups in their communities. 

PMID- 24315488
TI  - Tenodesis for restoration of distal interphalangeal joint flexion in unrepairable
      flexor digitorum profundus injuries.
AB  - PURPOSE: To describe in a cadaveric model a tenodesis procedure for restoring
      distal interphalangeal joint flexion in patients with unrepairable isolated
      flexor digitorum profundus (FDP) injuries. METHODS: In 16 fresh-frozen cadaveric
      fingers, the FDP tendon was transected 1 cm proximal to its insertion to simulate
      an isolated zone I laceration. The injury was reconstructed using a palmaris
      longus tendon graft to create a mechanical linkage between the interphalangeal
      joints, which restored coordinated interphalangeal joint flexion. Joint motion
      and the force required to flex and extend the fingers were tested before and
      after the tenodesis. RESULTS: After FDP zone I laceration, distal interphalangeal
      joint flexion with load applied to the flexor digitorum superficialis tendon
      averaged 2 degrees . The FDP flexion increased to a mean of 57 degrees  after the
      tenodesis. The sum of metacarpophalangeal, proximal interphalangeal and distal
      interphalangeal joint flexion averaged 186 degrees  before the tenodesis and
      increased to 233 degrees  after the tenodesis. The force required to achieve
      fingertip to palm contact and the force required to fully extend the proximal
      interphalangeal joint were not altered. CONCLUSIONS: In this cadaveric model,
      this tenodesis successfully restored coordinated interphalangeal joint flexion
      after a simulated zone I FDP laceration with improvements in distal
      interphalangeal joint flexion and composite finger flexion. Critical factors such
      as the effects of inflammation, edema, soft tissue healing, and scar formation
      could not be evaluated and would likely affect the outcomes of this procedure.
      The in vivo results of this procedure are not known. CLINICAL RELEVANCE: The
      potential use of this tenodesis for treating unrepairable isolated zone I FDP
      injuries was demonstrated in a cadaveric model. Further investigation of the
      outcomes and complications in vivo would be required before routine clinical use.

PMID- 24315489
TI  - Isolated ring-little finger metacarpal synostosis: a new classification system
      and treatment strategy.
AB  - PURPOSE: To devise a comprehensive classification system for isolated ring-little
      finger metacarpal synostosis that offers a clear guide to specific treatment for
      each variation of the deformity. METHODS: Based on the experience of 13 cases (20
      hands) of isolated ring-little finger metacarpal synostosis, we devised a
      classification system that takes into account 2 key pathological features of this
      malformation: the fourth-fifth intermetacarpal angle and the severity of
      hypoplasia of the fifth ray. In our classification, all patients were divided
      into 3 types, according to the fourth-fifth intermetacarpal angle, and each type
      was further subdivided into 2 subtypes according to the length of the fifth ray.
      RESULTS: All 20 hands could be classified according to our classification,
      including 2 hands of type A (both A1), 10 hands of type B (9 B1; 1 B2), and 8
      hands of type C (7 C1; 1 C2). Patients of different classification types received
      different treatments according to our proposed classification-related guidelines.
      It was also possible to classify all the cases found in literature according to
      this scheme. CONCLUSIONS: Our classification for ring-little finger metacarpal
      synostosis is simple and easy to remember. It is applicable to all possible
      variations of the congenital anomaly and can guide treatment for the whole
      spectrum of the deformity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

PMID- 24315490
TI  - Nerve transfers from branches to the flexor carpi radialis and pronator teres to
      reconstruct the radial nerve.
AB  - PURPOSE: To present our method and results for transferring branches of the
      median nerve for radial nerve palsy or posterior cord lesions. METHODS: We
      transferred 1 branch to the pronator teres to the branch to the extensor carpi
      radialis longus muscle and transferred the branch to the flexor carpi radialis to
      the posterior interosseous nerve. We carried out these transfers in 6 patients
      with radial nerve palsy or posterior cord lesions. We reviewed functional
      outcomes, Disabilities of the Arm, Shoulder and Hand scores, and Patient
      Evaluation Measure scores. RESULTS: After 20 months of follow-up evaluation, all
      patients had recovered extensor carpi radialis longus activity of M4. Activity of
      the extensor carpi ulnaris was M3 in 2 patients and M4 in 4 patients. Extensor
      pollicis longus activity was M4 in all 6 cases. Metacarpophalangeal extension was
      M4 in 4 cases and M3 in 2 cases. The mean Disabilities of the Arm, Shoulder, and
      Hand score was 26 (range, 7-43), and the mean Patient Evaluation Measure score
      was 34 (range, 24-53). CONCLUSIONS: Selective independent synergistic transfer of
      median nerve fascicles to the radial nerve branches has shown excellent results
      in the treatment of severe lesions of the radial nerve. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 24315491
TI  - The quality of upper extremity orthopedic care in liability claims filed and
      claims paid.
AB  - PURPOSE: To review a series of closed liability claims for upper extremity
      conditions to guide improvements for upper extremity care and thereby reduce the
      frequency of paid claims. METHODS: The authors, a team of 3 orthopedic surgeons
      and 3 nonphysician investigators experienced in closed claims research,
      investigated 108 closed upper extremity liability claims from a large United
      States-wide insurer for events that occurred between 1996 and 2009. We sought to
      determine the types of conditions, treatments, and surgeon factors common to
      claims made and claims paid. RESULTS: Liability claims were primarily for the
      care of common problems, such as fractures (n = 52; 48%) or degenerative
      conditions (n = 24; 26%), rather than complex challenging conditions or
      disorders, such as deficiencies treated with replantations or tissue transfers.
      The most common adverse outcomes in these claims were nonunion or malunion of
      fractures (n = 29; 27%), nerve injury (n = 20; 19%), and infection (n = 13; 12%).
      Most claims (n = 57; 53%) involved a permanent injury. The surgeon's operative
      skills were more commonly an issue in paid claims (n = 13; 45%) than in claims
      without payment (n = 14; 19%). Claims for mismanagement of fractures (n = 52; 48%
      of all claims) were more likely to result in payment (n = 20; 38%) than
      nonfracture claims (n = 10; 18%). CONCLUSIONS: This analysis suggests that the
      incidence of upper extremity claims made and claims paid may be reduced if
      surgeons acquire and maintain the knowledge and skills necessary for the care of
      the common conditions they encounter, including fractures. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic II.

PMID- 24315492
TI  - Corticosteroid injection with or without thumb spica cast for de Quervain
      tenosynovitis.
AB  - PURPOSE: To compare the corticosteroid injection (CSI) with or without thumb
      spica cast (TSC) for de Quervain tendinitis. METHODS: In this prospective trial,
      67 eligible patients with de Quervain tenosynovitis were randomly assigned into
      CSI + TSC (33 cases) and CSI (34 cases) groups. All patients received 40 mg of
      methylprednisolone acetate with 1 cc lidocaine 2% in the first dorsal compartment
      at the area of maximal point tenderness. The primary outcome was the treatment
      success rate, and the secondary outcome was the scale and quality of the
      treatment method using Quick Disabilities of Arm, Shoulder and Hand and visual
      analog scale scores. RESULTS: The groups had no differences in mean age, sex, and
      occupation. The visual analog scale and Quick Disabilities of the Arm, Shoulder
      and Hand scores were similar in both groups before the treatment. The treatment
      success rate was 93% in the CSI + TSC group and 69% in the CSI group. Although
      both methods improved the patients' conditions significantly in terms of
      relieving pain and functional ability, CSI + TSC had a significantly higher
      treatment success rate. CONCLUSIONS: The combined technique of corticosteroid
      injection and thumb spica casting was better than injection alone in the
      treatment of de Quervain tenosynovitis in terms of treatment success and
      functional outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

PMID- 24315493
TI  - The political economy of austerity and healthcare: cross-national analysis of
      expenditure changes in 27 European nations 1995-2011.
AB  - Why have patterns of healthcare spending varied during the Great Recession? Using
      cross-national, harmonised data for 27 EU countries from 1995 to 2011, we
      evaluated political, economic, and health system determinants of recent changes
      to healthcare expenditure. Data from EuroStat, the IMF, and World Bank (2013
      editions) were evaluated using multivariate random- and fixed-effects models,
      correcting for pre-existing time-trends. Reductions in government health
      expenditure were not significantly associated with magnitude of economic
      recessions (annual change in GDP, p=0.31, or cumulative decline, p=0.40 or debt
      crises (measured by public debt as a percentage of GDP, p=0.38 or per capita,
      p=0.83)). Nor did ideology of governing parties have an effect. In contrast, each
      $100 reduction in tax revenue was associated with a $2.72 drop in health spending
      (95% CI: $1.03-4.41). IMF borrowers were significantly more likely to reduce
      healthcare budgets than non-IMF borrowers (OR=3.88, 95% CI: 1.95 -7.74), even
      after correcting for potential confounding by indication. Exposure to lending
      from international financial institutions, tax revenue falls, and decisions to
      implement cuts correlate more closely than underlying economic conditions or
      orientation of political parties with healthcare expenditure change in EU member
      states.

PMID- 24315495
TI  - Psychogenic non-epileptic seizures in Iran.
AB  - PURPOSE: We investigated the demographic and clinical characteristics of
      psychogenic non-epileptic seizures (PNES) in patients in Iran. METHODS: In this
      prospective study, all patients with a clinical diagnosis of PNES (based on ictal
      recordings) were recruited at the outpatient epilepsy clinic at Shiraz University
      of Medical Sciences, from 2008 through 2013. The epileptologist interviewed all
      the patients. We investigated the demographic and clinical characteristics of
      PNES. RESULTS: Two hundred and forty-nine patients were diagnosed as having PNES.
      Two hundred and eleven patients had video-EEG recordings available and included
      in the study. One hundred and forty-one (66.8%) were female and 70 (33.2%) were
      male. There were no significant differences between our patients and previous
      reports regarding the clinical and semiological characteristics of PNES.
      CONCLUSION: Psychogenic non-epileptic seizures are relatively common at epilepsy
      clinics. It appears that an Islamic lifestyle (in Iran) has little influence on
      the clinical characteristics and manifestations of PNES, as we observed similar
      results as in most previous studies from other cultures.

PMID- 24315494
TI  - Lunatimonas lonarensis gen. nov., sp. nov., a haloalkaline bacterium of the
      family Cyclobacteriaceae with nitrate reducing activity.
AB  - Novel pinkish-orange pigmented, Gram-negative staining, half-moon shaped, non
      motile, strictly aerobic strains designated AK24(T) and AK26 were isolated from
      water and sediment samples of Lonar Lake, Buldhana district, Maharahstra, India.
      Both strains were positive for oxidase, catalase and beta-galactosidase
      activities. The predominant fatty acids were iso-C15:0 (41.5%), anteiso-C15:0
      (9.7%), iso-C17:0 3OH (9.6%), iso-C17:1 omega9c (10.2%) and C16:1 omega7c/C16:1
      omega6c/iso-C15:0 2OH (summed feature 3) (14.4%). The strains contained MK-7 as
      the major respiratory quinone, and phosphatidylethanolamine and five unidentified
      lipids as the polar lipids. Blast analysis of the 16S rRNA gene sequence of
      strain AK24(T) showed that it was closely related to Aquiflexum balticum, with a
      pair-wise sequence similarity of 91.6%, as well as to Fontibacter ferrireducens,
      Belliella baltica and Indibacter alkaliphilus (91.3, 91.2 and 91.2% pair-wise
      sequence similarity, respectively), but it only had between 88.6 and 91.0% pair
      wise sequence similarity to the rest of the family members. The MALDI-TOF assay
      reported no significant similarities for AK24(T) and AK26, since they potentially
      represented a new species. A MALDI MSP dendrogram showed close similarity between
      the two strains, but they maintained a distance from their phylogenetic
      neighbors. The genome of AK24(T) showed the presence of heavy metal tolerance
      genes, including the genes providing resistance to arsenic, cadmium, cobalt and
      zinc. A cluster of heat shock resistance genes was also found in the genome. Two
      lantibiotic producing genes, LanR and LasB, were also found in the genome of
      AK24(T). Strains AK24(T) and AK26 were very closely related to each other with
      99.5% pair-wise sequence similarity. Phylogenetic analysis indicated that the
      strains were members of the family Cyclobacteriaceae and they clustered with the
      genus Mariniradius, as well as with the genera Aquiflexum, Cecembia, Fontibacter,
      Indibacter, and Shivajiella. DNA-DNA hybridization between strains AK24(T) and
      AK26 showed a relatedness of 82% and their rep-PCR banding patterns were very
      similar. Based on data from the current polyphasic study, it is proposed that the
      isolates be placed in a new genus and species with the name Lunatimonas
      lonarensis gen. nov., sp. nov. The type strain of Lunatimonas lonarensis is
      AK24(T) (=JCM 18822(T)=MTCC 11627(T)).

PMID- 24315496
TI  - Hair loss with levetiracetam in five patients with epilepsy.
AB  - PURPOSE: To report cases of hair loss with levetiracetam (LEV) in epilepsy
      patient and summarise their demographic and clinical features. METHOD: All
      patients reported attended the epilepsy outpatient clinic of the West China
      Hospital, Sichuan University. Demographic and clinical information was obtained
      from medical records and by interview. All the patients were under regular follow
      up. RESULTS: Five epilepsy patients (4 females and 1 male) are reported. All
      developed hair loss within two months of starting LEV treatment. Three had
      idiopathic epilepsy, two symptomatic epilepsy. Three patients received LEV
      monotherapy, two combination treatment. None decided to switch away from LEV to
      another drug after developing hair loss, although the dose of LEV was reduced in
      one patient. CONCLUSION: Hair loss may be a rare side effect of LEV treatment in
      patients with epilepsy. LEV-related hair loss appears reversible if the dose is
      reduced or treatment is stopped.

PMID- 24315497
TI  - The accuracy of Internet search engines to predict diagnoses from symptoms can be
      assessed with a validated scoring system.
AB  - PURPOSE: To validate a scoring system that evaluates the ability of Internet
      search engines to correctly predict diagnoses when symptoms are used as search
      terms. METHODS: We developed a five point scoring system to evaluate the
      diagnostic accuracy of Internet search engines. We identified twenty diagnoses
      common to a primary care setting to validate the scoring system. One investigator
      entered the symptoms for each diagnosis into three Internet search engines
      (Google, Bing, and Ask) and saved the first five webpages from each search. Other
      investigators reviewed the webpages and assigned a diagnostic accuracy score.
      They rescored a random sample of webpages two weeks later. To validate the five
      point scoring system, we calculated convergent validity and test-retest
      reliability using Kendall's W and Spearman's rho, respectively. We used the
      Kruskal-Wallis test to look for differences in accuracy scores for the three
      Internet search engines. RESULTS: A total of 600 webpages were reviewed.
      Kendall's W for the raters was 0.71 (p<0.0001). Spearman's rho for test-retest
      reliability was 0.72 (p<0.0001). There was no difference in scores based on
      Internet search engine. We found a significant difference in scores based on the
      webpage's order on the Internet search engine webpage (p=0.007). Pairwise
      comparisons revealed higher scores in the first webpages vs. the fourth (corr
      p=0.009) and fifth (corr p=0.017). However, this significance was lost when
      creating composite scores. CONCLUSIONS: The five point scoring system to assess
      diagnostic accuracy of Internet search engines is a valid and reliable
      instrument. The scoring system may be used in future Internet research.

PMID- 24315499
TI  - Appropriate assessment of the functional consequences of platelet cyclooxygenase
      1 inhibition by aspirin in vivo.

PMID- 24315498
TI  - Synergistic association of DNA repair relevant gene polymorphisms with the risk
      of coronary artery disease in northeastern Han Chinese.
AB  - Evidence is mounting suggesting that DNA damage is implicated in the development
      and progression of atherosclerosis. To yield more information, we focused on six
      well-characterized polymorphisms from four DNA repair-relevant candidate genes,
      viz. XRCC1 (rs1799782 and rs25487), XRCC3 (rs861539), MTHFR (rs1801133 and
      rs4846049), and NQO1 (rs1800566), to identify and characterize their potential
      gene-to-gene interactions in susceptibility to coronary artery disease (CAD) in
      Han Chinese. This was a hospital-based case-control study involving 1142 patients
      diagnosed with CAD and 1106 age- and gender-matched controls. All participants
      were angiographically confirmed. Risk estimates were expressed as odds ratio (OR)
      and 95% confidence interval (95% CI). All six examined polymorphisms met Hardy
      Weinberg equilibrium. Overall there were significant differences in the
      genotype/allele distributions of MTHFR gene rs1801133 and rs4846049 (both P <=
      0.005), and in the genotype distributions of XRCC1 gene rs1799782 (P = 0.002)
      between patients and controls. The adjusted risk of having CAD was more evident
      for rs1799782 (OR = 1.53; 95% CI: 1.16-2.02; P = 0.003), rs1801133 (OR = 1.54;
      95% CI: 1.22-1.94; P < 0.001), and rs4846049 (OR = 1.74; 95% CI: 1.13-2.69; P =
      0.013) under the recessive model. Interaction analyses indicated that the overall
      best multifactor dimensionality reduction (MDR) model included rs4846049,
      rs1801133, and rs1799782, and this model had a maximal testing accuracy of 0.6885
      and a cross-validation consistency of 10 out of 10 (P = 0.0030). Further
      interaction entropy graph bore out the validity of this MDR model. Taken
      together, our findings demonstrate a contributory role of genetic defects in
      XRCC1 and MTHFR genes, both individually and interactively, in the development of
      CAD in Han Chinese.

PMID- 24315500
TI  - Evaluation of indirect microparticle activity and parameters of thrombin
      generation test in healthy infants.
AB  - INTRODUCTION: Circulating microparticles support thrombin generation. The aim of
      this study is to determine the indirect microparticle activity and the parameters
      of thrombin generation in healthy infants. MATERIALS AND METHODS: A total of 85
      infants who were brought to follow-up visits were taken into the study. Blood
      samples were collected. Thrombin generation parameters and indirect microparticle
      activity were measured. RESULTS: The infants were divided into four groups
      according to the time of follow-up visits. Mean ages were 1.18 +/- 0.19 months in
      Group 1, 6.15 +/- 0.16 months in Group 2, 12.38 +/- 0.46 months in Group 3 and
      24.53 +/- 0.39 months in Group 4, respectively. There was no statistical
      difference among the age-based groups with respect to the indirect microparticle
      activity. The lag time and the TTP levels in Group 1 were lower than that found
      in Group 2. The ETP and peak levels were higher in Group 1 than that of Group 2.
      The ETP and peak levels in Group 2 were found lower than those found in older
      children, but the TTP level was found relatively higher. Statistically
      correlations were found between indirect microparticle activity and all
      parameters of thrombin generation. CONCLUSIONS: The absence of a difference in
      terms of age-based microparticle levels may suggest that the features of
      microparticles in healthy children of this age group are similar. Age-dependent
      changes in thrombin generation parameters may suggest a regulation mechanism for
      the thrombin generation system over the first years of life. The results may
      provide mean values for indirect microparticle activity and thrombin generation
      in this healthy group.

PMID- 24315501
TI  - Newborn pulse oximetry screening to detect critical congenital heart disease.
AB  - OBJECTIVES: To describe current practice and clarify provider opinion in the US
      with regard to newborn pulse oximetry screening (NPOx) for critical congenital
      heart disease. STUDY DESIGN: An internet-based questionnaire was forwarded to
      general pediatricians, neonatologists, and family medicine physicians. Physicians
      were surveyed regarding involvement in newborn medicine, knowledge of NPOx
      recommendations, and opinions regarding screening. NPOx protocol specifics were
      also queried. RESULTS: Survey responses (n = 481) were received with 349
      respondents involved in newborn medicine. Forty-nine percent (95% CI 44%-54%) of
      those involved in newborn medicine practice at a hospital with a NPOx protocol.
      Sixty-six percent of providers endorsed it as an effective tool, 20% required
      more education, 11% questioned its sensitivity, and 3% had no opinion. Sixty-five
      percent of providers were aware of recent state legislation mandating its use and
      46% reported awareness of the addition of NPOx to the Recommended Uniform
      Screening Panel. Eighty-four percent of providers who practice at a hospital
      without a NPOx protocol were interested in its implementation. NPOx protocols
      varied and were not uniform with differences in time of test, location of probe,
      and values considered positive. CONCLUSIONS: NPOx has grown in its prevalence and
      acceptance in clinical practice, yet is far from universal in its application and
      design despite the recent American Academy of Pediatrics endorsement and its
      addition to the Recommended Uniform Screening Panel. The majority of physicians
      involved in newborn medicine deemed it an effective tool.

PMID- 24315502
TI  - Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma.
AB  - BACKGROUND: Asthma phenotyping can facilitate understanding of disease
      pathogenesis and potential targeted therapies. OBJECTIVE: To further characterize
      the distinguishing features of phenotypic groups in difficult-to-treat asthma.
      METHODS: Children ages 6-11 years (n = 518) and adolescents and adults ages >=12
      years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology
      and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were
      evaluated in this post hoc cluster analysis. Analyzed variables included sex,
      race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke
      exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the
      hierarchical clustering algorithm with the Ward minimum variance method. The
      results were compared among clusters by chi(2) analysis; variables with
      significant (P < .05) differences among clusters were considered as
      distinguishing feature candidates. Associations among clusters and asthma-related
      health outcomes were assessed in multivariable analyses by adjusting for
      socioeconomic status, environmental exposures, and intensity of therapy. RESULTS:
      Five clusters were identified in each age stratum. Sex, atopic status, and
      nonwhite race were distinguishing variables in both strata; passive smoke
      exposure was distinguishing in children and aspirin sensitivity in adolescents
      and adults. Clusters were not related to outcomes in children, but 2 adult and
      adolescent clusters distinguished by nonwhite race and aspirin sensitivity
      manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster
      experienced more frequent asthma exacerbations (P < .0001). CONCLUSION: Distinct
      phenotypes appear to exist in patients with severe or difficult-to-treat asthma,
      which is related to outcomes in adolescents and adults but not in children. The
      study of the therapeutic implications of these phenotypes is warranted.

PMID- 24315503
TI  - Cigarette smoking as a stigma: evidence from France.
AB  - BACKGROUND: There is growing evidence that cigarette smoking has become a
      stigmatized behaviour, at least in western countries, and there is ongoing debate
      among experts about whether or not such stigma should be an instrument of anti
      tobacco policy. METHODS: We investigated French non-smokers attitudes toward
      cigarette smokers, using data from a telephone survey carried out in 2010 among a
      representative random sample of non-smokers aged 15-75 (N=3091). We carried out a
      cluster analysis to build contrasted attitudinal profiles and we also computed a
      score of stigmatization. RESULTS: We found evidence for the existence of stigma
      associated with cigarette smoking in France: a majority of French non-smokers
      would not date a smoker, nor hire one to take care of their children. The cluster
      analysis identified four contrasting profiles, corresponding to different levels
      of stigmatization, including one cluster whose respondents demonstrated strong
      levels of moral condemnation and social rejection of smokers. Older people, those
      with a lower educational level and those reporting financial difficulties were
      more prone to stigmatize smokers, while those who reported that somebody smoked
      in their home were less likely to do so. Those who had never smoked and those who
      abstained from alcohol were more prone to stigmatize smokers. Obese people were
      also more likely to do so (in bivariate analysis only). CONCLUSION: The process
      of tobacco stigmatization seems well-advanced in France, despite a cultural
      context that may be less permeable to this process. Further research is needed as
      our results raise some questions regarding its efficiency as a policy tool.
      First, people who are familiar with smokers are less prone to stigmatize them.
      More generally, simultaneously stigmatizing several categories of people may
      provide each of these same categories with stereotyped 'others' onto whom they
      can deflect their stigma.

PMID- 24315504
TI  - Does informing people who inject drugs of their hepatitis C status influence
      their injecting behaviour? Analysis of the Networks II study.
AB  - BACKGROUND: People who inject drugs (PWID) are at risk of hepatitis C virus
      (HCV). It is plausible that PWID who receive a diagnosis of HCV will reduce their
      injecting risk out of concern for their injecting partners, although evidence for
      this is currently limited. The aim of this study was to investigate whether
      informing PWID of their HCV diagnosis was associated with a change in injecting
      behaviour. METHODS: Prospective, longitudinal study of PWID recruited from street
      drug markets across Melbourne, Australia. Interviews and HCV testing were
      conducted at 3-monthly intervals. The association between receiving a diagnosis
      of HCV and (i) injecting frequency and (ii) injecting equipment borrowing, was
      examined using generalized estimating equations (GEE) analysis. RESULTS: Thirty
      five individuals received a diagnosis of HCV during the study period. Receiving a
      diagnosis of HCV was associated with a decrease of 0.35 injections per month
      (p=0.046) but there was no change in injecting equipment borrowing (p=0.750).
      CONCLUSIONS: A small reduction in injecting frequency was observed in PWID who
      received a diagnosis of HCV. This finding should be investigated further in
      larger studies examining a wider range of injecting risk behaviours.

PMID- 24315505
TI  - Clinical management of youth with gender dysphoria in Vancouver.
AB  - OBJECTIVE: To describe patient characteristics at presentation, treatment, and
      response to treatment in youth with gender dysphoria. STUDY DESIGN: A
      retrospective chart review of 84 youth with a diagnosis of gender dysphoria seen
      at BC Children's Hospital from 1998-2011. RESULTS: Of the 84 patients, 45 (54%)
      identified as female-to-male (FtM), 37 (44%) as male-to-female (MtF), and 2 (2%)
      as natal males who were undecided. Median age of presentation was 16.9 years
      (range 11.4-19.8 years) and 16.6 years (range 12.3-22.5 years) for FtM and MtF
      youth, respectively. Gonadotropin-releasing hormone analog treatment was
      prescribed in 27 (32%) patients. One FtM patient developed sterile abscesses with
      leuprolide acetate; he was switched to triptorelin and tolerated this well. Cross
      sex hormones were prescribed in 63 of 84 patients (39 FtM vs 24 MtF, P < .02).
      Median age at initiation of testosterone injections in FtM patients was 17.3
      years (range 13.7-19.8 years); median age at initiation of estrogen therapy in
      MtF patients was 17.9 years (range 13.3-22.3 years). Three patients stopped cross
      sex hormones temporarily due to psychiatric comorbidities (2 FtM) and distress
      over androgenic alopecia (1 FtM). No severe complications were noted in patients
      treated with testosterone or estrogen. CONCLUSION: Treatment with gonadotropin
      releasing hormone analog and/or cross-sex hormones, in collaboration with
      transgender-competent mental health professionals, is an intervention that
      appears to be appropriate in carefully selected youth with gender dysphoria. Long
      term follow-up studies are needed to determine the safety of these treatments in
      this age group.

PMID- 24315506
TI  - Reply: To PMID 23351600.

PMID- 24315507
TI  - Pediatric acute liver failure and immune dysregulation.

PMID- 24315508
TI  - Maternal body-mass index and cord blood circulating endothelial colony-forming
      cells.
AB  - OBJECTIVE: Endothelial colony-forming cells (ECFCs) are a subset of circulating
      endothelial progenitor cells that are particularly abundant in umbilical cord
      blood. We sought to determine whether ECFC abundance in cord blood is associated
      with maternal body-mass index (BMI) in nonpathologic pregnancies. STUDY DESIGN:
      We measured the level of ECFCs in the cord blood of neonates (n = 27) born from
      non-obese healthy mothers with nonpathologic pregnancies and examined whether
      ECFC abundance correlated with maternal BMI. We also examined the effect of
      maternal BMI on ECFC phenotype and function using angiogenic and vasculogenic
      assays. RESULTS: We observed variation in ECFC abundance among subjects and found
      a positive correlation between prepregnancy maternal BMI and ECFC content (r =
      0.51, P = .007), which was independent of other obstetric factors. Despite this
      variation, ECFC phenotype and functionality were deemed normal and highly similar
      between subjects with maternal BMI <25 kg/m(2) and BMI between 25-30 kg/m(2),
      including the ability to form vascular networks in vivo. CONCLUSIONS: This study
      underlines the need to consider maternal BMI as a potential confounding factor
      for cord blood levels of ECFCs in future comparative studies between healthy and
      pathologic pregnancies.

PMID- 24315510
TI  - [Joint Position Statement of the SEEN-SECO-SEEDO-SED Societies on metabolic
      surgery for type 2 diabetes mellitus"].

PMID- 24315509
TI  - Cardiometabolic risk factors and fat distribution in children and adolescents.
AB  - OBJECTIVES: To determine if cardiometabolic risk factors have differential
      associations with the proportion of fat distributed in the trunk, leg, and arm,
      in White and African American children and adolescents. STUDY DESIGN: The sample
      included 391 White and African American 5- to 18 year-olds. Total and regional
      (trunk, leg, and arm) fat were measured by dual energy X-ray absorptiometry.
      Resting blood pressure and fasting triglycerides, high density lipoprotein
      cholesterol (HDL-C), glucose, insulin, and C-reactive protein were measured in a
      clinical setting. Insulin resistance was determined with the homeostatic model of
      insulin resistance. Multivariable linear and logistic regression models were used
      to examine associations between each cardiometabolic risk factor and proportion
      of fat (trunk, leg, or arm fat divided by whole body fat), with whole body fat,
      age, sex, race, sexual maturity status, and self-reported physical activity as
      covariates. RESULTS: Higher odds of low HDL-C, high triglycerides, insulin
      resistance, and high C-reactive protein were associated with % trunk fat. Lower
      odds of low HDL-C, high triglycerides, and insulin resistance were associated
      with % leg fat. No cardiometabolic risk factor was associated with % arm fat.
      CONCLUSIONS: Cardiometabolic risk factors in children and adolescents were
      attenuated when a larger proportion of fat was distributed in the leg. The
      clinical assessment of children's fat distribution may be useful in determining
      cardiometabolic risk.

PMID- 24315511
TI  - Prevalence of incidental perihepatic adhesions at laparotomy in cases of ovarian
      cancer.

PMID- 24315512
TI  - Minimally invasive resection of brainstem cavernous malformations: surgical
      approaches and clinical experiences with 38 patients.
AB  - OBJECTIVE: The purpose of this study is to provide a retrospective review of
      patients with brain stem cavernous malformation (BSCM) at single institution.
      METHODS: Clinical courses were retrospectively reviewed for 38 consecutive
      patients who underwent microsurgical resection of symptomatic BSCMs in the sub
      acute phase between January 2000 and December 2009. Microsurgery was performed
      with the help of intraoperative neuronavigation and neurophysiological
      monitoring. The baseline information of patients, lesion characteristics,
      surgical approaches, and follow-up outcomes were analyzed. RESULTS: All 38
      patients received microsurgical resections without surgery-related mortality, and
      37 patients were completely extirpated. 21 patients who experienced neurological
      deficits had functional improvement after surgery, 15 patients had no change in
      the neurological status over time to their preoperative condition or better, and
      2 patients deteriorated. During the follow-up, 28 patients had resumed activities
      of daily living (KPS=90-100), 8 patients were able to self-care with some efforts
      (KPS=70-80) and other 2 patients needed considerable assistance. None of the
      operated patient had recurrent hemorrhage. Postoperative complications included
      new cranial nerve deficits in 13 patients, motor deficits in 3 patients, and new
      sensory disturbances in 6 patients. CONCLUSION: Complete surgical resection could
      be achieved through careful preoperative planning, selection of the optimal
      operative approach, a meticulous microsurgical technique and intraoperative
      navigation. However, taking into account the relatively high postoperative
      morbidity, complete resection is not always the goal for BSCMs, especially for
      those deep-seated lesions.

PMID- 24315513
TI  - Advance directives, advance care planning, and shared decision making: promoting
      synergy over exclusivity in contemporary context.

PMID- 24315514
TI  - Single-fraction radiotherapy for palliation of myelofibrosis-related extremity
      pain syndrome.

PMID- 24315515
TI  - Red eye as the primary manifestation of Wegener's granulomatosis.

PMID- 24315516
TI  - Multifocal hematogenous vertebral osteomyelitis due to Parvimonas micra and a
      subsequent pleural effusion in a diabetic patient.

PMID- 24315517
TI  - The lag time between onset of symptoms, medical encounter, and initiation of
      disease modifying antirheumatic drugs in patients with rheumatoid arthritis.

PMID- 24315518
TI  - Elastic compression stockings--is there any benefit?

PMID- 24315519
TI  - Systemic AL-amyloidosis.

PMID- 24315520
TI  - Clinical and cost-effectiveness of compression hosiery versus compression
      bandages in treatment of venous leg ulcers (Venous leg Ulcer Study IV, VenUS IV):
      a randomised controlled trial.
AB  - BACKGROUND: Drawbacks exist with the standard treatment (four-layer compression
      bandages) for venous leg ulcers. We have therefore compared the clinical
      effectiveness and cost-effectiveness of two-layer compression hosiery with the
      four-layer bandage for the treatment of such ulcers. METHODS: We undertook this
      pragmatic, open, randomised controlled trial with two parallel groups in 34
      centres in England and Northern Ireland. The centres were community nurse teams
      or services, family doctor practices, leg ulcer clinics, tissue viability clinics
      or services, and wound clinics. Participants were aged 18 years or older with a
      venous leg ulcer and an ankle brachial pressure index of at least 0.8, and were
      tolerant of high compression. We randomly allocated participants (1:1) to receive
      two-layer compression hosiery or a four-layer bandage, using a remote
      randomisation service and prevalidated computer randomisation program.
      Participants were stratified by ulcer duration and ulcer area with permuted
      blocks (block sizes four and six). The primary endpoint was time to ulcer
      healing, with a maximum follow-up of 12 months. Although participants and health
      care providers were not masked to treatment allocation, the primary endpoint was
      measured by masked assessment of photographs. Primary analysis was intention to
      treat with Cox regression, with adjustment for ulcer area, ulcer duration,
      physical mobility, and centre. This trial is registered with the ISRCTN register,
      number ISRCTN49373072. FINDINGS: We randomly allocated 457 participants to the
      two treatment groups: 230 to two-layer hosiery and 227 to the four-layer bandage,
      of whom 453 (230 hosiery and 223 bandage) contributed data for analysis. Median
      time to ulcer healing was 99 days (95% CI 84-126) in the hosiery group and 98
      days (85-112) in the bandage group, and the proportion of ulcers healing was much
      the same in the two groups (70.9% hosiery and 70.4% bandage). More hosiery
      participants changed their allocated treatment (38.3% hosiery vs 27.0% bandage;
      p=0.02). 300 participants had 895 adverse events, of which 85 (9.5%) were classed
      as serious but unrelated to trial treatment. INTERPRETATION: Two-layer
      compression hosiery is a viable alternative to the four-layer bandage-it is
      equally as effective at healing venous leg ulcers. However, a higher rate of
      treatment changes in participants in the hosiery group than in the bandage group
      suggests that hosiery might not be suitable for all patients. FUNDING: NIHR
      Health Technology Assessment programme (07/60/26).

PMID- 24315523
TI  - Stockings before bandages: an option for venous ulcers.

PMID- 24315524
TI  - In vitro assessment of 3-T MRI issues for a bioabsorbable, coronary artery
      scaffold with metallic markers.
AB  - OBJECTIVE: Coronary artery stents are made from metallic mesh and, therefore, to
      ensure patient safety, these implants must be evaluated to determine risks
      associated with MRI. Recently, bioabsorbable scaffolds, which have metallic
      markers, have been developed for use in the coronary arteries. Because of the
      metallic materials, these implants may present issues for patients undergoing
      MRI. Therefore, the objective of this investigation was to assess MRI issues
      (i.e., magnetic field interactions, MRI-related heating, and artifacts at 3 T)
      for a new bioabsorbable, coronary artery scaffold with metallic markers. METHODS:
      A bioabsorbable, coronary artery scaffold (Mirage Microfiber Scaffold) underwent
      assessments for magnetic field interactions, MRI-related heating, and artifacts
      at 3-Tesla using standard techniques. MRI-related heating was evaluated with the
      scaffold placed in a gelled-saline-filled phantom and MRI was performed at an MR
      system reported, whole body averaged SAR of 2.9W/kg for 15 minutes. Artifacts
      were characterized using T1-weighted spin echo and gradient echo, pulse
      sequences. RESULTS: There were no magnetic field interactions. The highest
      temperature rise was 1.6 degrees C (highest background temperature rise, 1.6
      degrees C). Artifacts were relatively small in relation to the size and shape of
      this coronary artery scaffold. Notably, the lumen of the scaffold could be
      visualized on the GRE pulse sequence. CONCLUSION: The results demonstrated that
      the coronary artery scaffold is acceptable (or "MR conditional," using current
      MRI labeling terminology) for a patient undergoing an MRI procedure at 3 T or
      less. To our knowledge, this is the first bioabsorbable, coronary artery scaffold
      that has been evaluated for MRI issues.

PMID- 24315521
TI  - Compression stockings to prevent post-thrombotic syndrome: a randomised placebo
      controlled trial.
AB  - BACKGROUND: Post-thrombotic syndrome (PTS) is a common and burdensome
      complication of deep venous thrombosis (DVT). Previous trials suggesting benefit
      of elastic compression stockings (ECS) to prevent PTS were small, single-centre
      studies without placebo control. We aimed to assess the efficacy of ECS, compared
      with placebo stockings, for the prevention of PTS. METHODS: We did a multicentre
      randomised placebo-controlled trial of active versus placebo ECS used for 2 years
      to prevent PTS after a first proximal DVT in centres in Canada and the USA.
      Patients were randomly assigned to study groups with a web-based randomisation
      system. Patients presenting with a first symptomatic, proximal DVT were
      potentially eligible to participate. They were excluded if the use of compression
      stockings was contraindicated, they had an expected lifespan of less than 6
      months, geographical inaccessibility precluded return for follow-up visits, they
      were unable to apply stockings, or they received thrombolytic therapy for the
      initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months
      or later using Ginsberg's criteria (leg pain and swelling of >=1 month duration).
      We used a modified intention to treat Cox regression analysis, supplemented by a
      prespecified per-protocol analysis of patients who reported frequent use of their
      allocated treatment. This study is registered with ClinicalTrials.gov, number
      NCT00143598, and Current Controlled Trials, number ISRCTN71334751. FINDINGS: From
      2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396
      placebo ECS. The cumulative incidence of PTS was 14.2% in active ECS versus 12.7%
      in placebo ECS (hazard ratio adjusted for centre 1.13, 95% CI 0.73-1.76; p=0.58).
      Results were similar in a prespecified per-protocol analysis of patients who
      reported frequent use of stockings. INTERPRETATION: ECS did not prevent PTS after
      a first proximal DVT, hence our findings do not support routine wearing of ECS
      after DVT. FUNDING: Canadian Institutes of Health Research.

PMID- 24315525
TI  - [Type 2 diabetes and pregnancy: epidemiology and obstetrical consequences. A 97
      women continuous series].
AB  - OBJECTIVES: To update the epidemiologic data of pregnant women with type 2
      diabetes and to assess obstetrical outcomes. PATIENTS AND METHODS: The pregnant
      women with type 2 diabetes who delivered between 2002 and 2010 were
      systematically involved in an observational study. Maternal and fetal outcomes
      were reviewed, as well as the potential impact of preconceptional management. The
      presented data were compared with those from the 2010 French perinatal study.
      RESULTS: A rise in the incidence of type 2 diabetes was observed during the study
      period (from 0.19% to 0.35% between 2002 and 2010). Women with diabetes (n=97)
      were older and had a higher BMI than the general population (>35years: 49% vs
      19%, P<0.00001, BMI>25: 86% vs 27.2, P<0.00001). The delivery mode was, for half
      of these women with diabetes, a C-section. Pregnancy was scheduled in only 4% of
      cases. Compared to the general population, prematurity rate was multiplied by 6
      (28.7% vs 4.7%, P<0.0001) and the malformation rate by 3.2 (7.22% vs 2.2%,
      P<0.00001). CONCLUSION: Obstetrical complications were more frequent than in the
      general population. Preconception care was almost inexistent, despite its
      potential benefits for the mother and child.

PMID- 24315522
TI  - Schizophrenia: an integrated sociodevelopmental-cognitive model.
AB  - Schizophrenia remains a major burden on patients and society. The dopamine
      hypothesis attempts to explain the pathogenic mechanisms of the disorder, and the
      neurodevelopmental hypothesis the origins. In the past 10 years an alternative,
      the cognitive model, has gained popularity. However, the first two theories have
      not been satisfactorily integrated, and the most influential iteration of the
      cognitive model makes no mention of dopamine, neurodevelopment, or indeed the
      brain. In this Review we show that developmental alterations secondary to variant
      genes, early hazards to the brain, and childhood adversity sensitise the dopamine
      system, and result in excessive presynaptic dopamine synthesis and release.
      Social adversity biases the cognitive schema that the individual uses to
      interpret experiences towards paranoid interpretations. Subsequent stress results
      in dysregulated dopamine release, causing the misattribution of salience to
      stimuli, which are then misinterpreted by the biased cognitive processes. The
      resulting paranoia and hallucinations in turn cause further stress, and
      eventually repeated dopamine dysregulation hardwires the psychotic beliefs.
      Finally, we consider the implications of this model for understanding and
      treatment of schizophrenia. 

PMID- 24315526
TI  - Deleterious effects of aggressive rapid crystalloid resuscitation on treatment of
      hyperinflammatory response and lung injury induced by hemorrhage in aging rats.
AB  - BACKGROUND: Large-volume, rapid crystalloid infusion may increase endothelial
      cell damage and induce shear stress, potentially leading to multiple-organ
      dysfunction syndrome. Limited guideline data for fluid administration are
      currently available, especially for the aging population. The aim of the present
      study was to compare the degree of organ damage in conscious aging rats when
      different resuscitation speeds were used during the treatment of hemorrhagic
      shock (HS). METHODS: Eighteen aging male Wistar-Kyoto rats were randomly divided
      into the following three groups: the control group, 30-min rapid resuscitation
      group, and 12-h slow resuscitation group. To mimic HS, 40% of the total blood
      volume was withdrawn. Fluid resuscitation (1:3) was given at 30 min after the
      blood withdrawal. Blood biochemical parameters including glucose, lactic acid,
      and lactate dehydrogenase (LDH) were measured along with the levels of serum and
      bronchoalveolar lavage fluid, tumor necrosis factor alpha (TNF-alpha), and
      interleukin 10 by enzyme-linked immunosorbent assay. The lungs were examined for
      pathologic changes, and the injury score at 24 h after HS was calculated.
      RESULTS: Compared with slow-rate resuscitation, initially rapid and immediate
      resuscitation significantly increased the serum levels of glucose, LDH, and
      proinflammatory cytokines (TNF-alpha and interleukin 10), and bronchoalveolar
      lavage fluid levels of white blood cells, TNF-alpha, and LDH as well as produced
      pathologic changes in the organ. The lung injury scores were higher after induced
      HS in aging rats. CONCLUSIONS: The slow and continuous (12 h) fluid resuscitation
      rate ameliorated HS-induced organ damage in conscious aging rats.

PMID- 24315527
TI  - Africa - The Continent of the future - Welcome to the 2014 ISP.

PMID- 24315528
TI  - Direct proteomic mapping of Streptomyces roseosporus NRRL 11379 with precursor
      and insights into daptomycin biosynthesis.
AB  - This first-attempt study provided liquid chromatography tandem mass (LC-MS/MS)
      proteomics approach to explore precursor effects on daptomycin synthesis from
      Streptomyces roseosporus NRRL 11379. Among all, 357 and 691 differential proteins
      from 601 proteins in precursor group (144 h+) and 935 proteins in non-precursor
      group (144 h-) were identified, respectively. Through the simulation of the 2D
      protein mapping, most proteins were found in isoelectric points ranged of 4.5
      10.0 as well as Mws ranged 10-100 kDa. As a result, LC-MS/MS analysis was
      consistence with the analytical results of two-dimensional electrophoresis (2DE)
      but provided much intact profiles of proteins by precursor effect on S.
      roseosporus. To have more insight exploration, differential proteins associated
      to Streptomyces spp. were defined into 14 groups of their functional
      classification. The major differential proteins were in transport/membrane
      functional group with an occupation of 12.4% for 144 h+ and 5.2% for 144 h-,
      respectively. LC-MS/MS results as a direct proteomic mapping approach reveal more
      daptomycin synthetic and regulation-related proteins from precursor group in
      terms of methyltransferase, ATP-binding cassette (ABC) transporters, resistance
      proteins and regulators.

PMID- 24315529
TI  - Trehalose suppresses antibody aggregation during the culture of Chinese hamster
      ovary cells.
AB  - The aggregation of therapeutic antibodies during the manufacturing process is
      problematic because of the potential risks posed by the aggregates, such as an
      unexpected immune response. One of the hallmark effects of trehalose, a
      disaccharide consisting of two alpha-glucose units, is as a chemical chaperone
      with anti-aggregation activity. In this study, Chinese hamster ovary (CHO) cell
      line producing a diabody-type bispecific antibody were cultured in medium
      containing trehalose and the aggregation of the secreted proteins during the
      culture process was analyzed. An analysis of the various forms of the antibody
      (monomeric, dimeric, and large aggregates) showed that trehalose decreased the
      relative content of large aggregates by two thirds. The aggregation kinetics
      indicated that trehalose directly inhibited the polymerization and aggregation
      steps in a nucleation-dependent aggregation mechanism. Moreover, both specific
      and volumetric antibody production were increased in CHO cells cultured in
      trehalose-containing medium. Thus, the addition of trehalose to recombinant CHO
      cell cultures would offer a practical strategy for quality improvement in the
      production of therapeutic antibodies.

PMID- 24315530
TI  - Functional analysis of cis-aconitate decarboxylase and trans-aconitate metabolism
      in riboflavin-producing filamentous Ashbya gossypii.
AB  - In Ashbya gossypii, isocitrate lyase (ICL1) is a very crucial enzyme for
      riboflavin production. Itaconate, the inhibitor of ICL1, has been used as an
      antimetabolite for mutagenic studies in A. gossypii. It has been reported that
      itaconate is produced from cis-aconitate by cis-aconitate decarboxylase (CAD1) in
      Aspergillus terreus. In this study, identification of CAD1 gene and determination
      of the presence of itaconate in the riboflavin biosynthetic pathway in A.
      gossypii were carried out to confirm itaconate metabolism. Although no CAD1
      candidate gene was found and no itaconate production was observed, cis- and trans
      aconitate were detected in the riboflavin production phase. It is known that
      trans-aconitate inhibits aconitase (ACO1) in the tricarboxylic acid cycle. In A.
      gossypii, the transcription level of AGR110Wp, the homolog of trans-aconitate 3
      methyltransferase (TMT1), was enhanced by almost threefold during riboflavin
      production than that during its growth phase. TMT1 catalyzes the methylation
      reaction of trans-aconitate in Saccharomyces cerevisiae. Thus, these results
      suggest that the enhancement of the transcription level of this TMT1 homolog
      decreases the trans-aconitate level, which may mitigate the inhibition of ACO1 by
      oxidative stress in the riboflavin biosynthetic pathway in A. gossypii. This is a
      novel finding in A. gossypii, which may open new metabolic engineering ideas for
      improving riboflavin productivity.

PMID- 24315531
TI  - Increase in lactate yield by growing Corynebacterium glutamicum in a
      bioelectrochemical reactor.
AB  - Under conditions conductive to growth, Corynebacterium glutamicum showed higher
      lactate yield from glucose (1.62 +/- 0.04) in a bioelectrochemical reactor
      including 0.2 mM of anthraquinone 2,6-disulfonate with the electrode potential
      regulated at -0.6 V (vs. Ag/AgCl) than in a non-regulated environment (1.10 +/-
      0.03), clarifying that low cathodic potential is beneficial for lactate
      production.

PMID- 24315532
TI  - Cis-element of the rice PDIL2-3 promoter is responsible for inducing the
      endoplasmic reticulum stress response.
AB  - A protein disulfide isomerase (PDI) family oxidoreductase, PDIL2-3, is involved
      in endoplasmic reticulum (ER) stress responses in rice. We identified a critical
      cis-element required for induction of the ER stress response. The activation of
      PDIL2-3 in response to ER stress strongly depends on the IRE1-OsbZIP50 signaling
      pathway.

PMID- 24315533
TI  - Epistemological beliefs and the Self-efficacy Scale in nursing students.
AB  - BACKGROUND: Epistemological beliefs in their most general form define an
      individual's subjective beliefs about what knowledge is and how knowing and
      learning occur. OBJECTIVES: To investigate epistemological beliefs and the Self
      efficacy Scale in nursing students. DESIGN: Prospective survey study. SETTINGS:
      University School of Nursing. PARTICIPANTS: Nursing students. METHODS: Outcome
      parameters included Nurses' Descriptive Characteristics Data Form,
      Epistemological Beliefs Questionnaire and Self-efficacy Scale. RESULTS: As for
      the subscales of epistemological beliefs, Effort Subscale was 38.89 +/- 11.62,
      Ability Subscale was 24.02 +/- 6.19 and Unchanging Truth Subscale was 30.65 +/-
      5.74. Total score of the self-efficacy subscales was 74.39 +/- 13.59. It has been
      determined that the majority (60.8%) of nursing students have chosen the nursing
      profession willingly, 82.8% of them like the nursing profession and 59.8% of
      students have a good perception of their own academic achievements. CONCLUSIONS:
      Understanding student's epistemological beliefs, trying to improve them and
      creating suitable learning environments for the development of self-efficacy
      should be the aim of an education that values individual differences.

PMID- 24315534
TI  - Detecting diversity: emerging methods to estimate species diversity.
AB  - Estimates of species richness and diversity are central to community and
      macroecology and are frequently used in conservation planning. Commonly used
      diversity metrics account for undetected species primarily by controlling for
      sampling effort. Yet the probability of detecting an individual can vary among
      species, observers, survey methods, and sites. We review emerging methods to
      estimate alpha, beta, gamma, and metacommunity diversity through hierarchical
      multispecies occupancy models (MSOMs) and multispecies abundance models (MSAMs)
      that explicitly incorporate observation error in the detection process for
      species or individuals. We examine advantages, limitations, and assumptions of
      these detection-based hierarchical models for estimating species diversity.
      Accounting for imperfect detection using these approaches has influenced
      conclusions of comparative community studies and creates new opportunities for
      testing theory. 

PMID- 24315535
TI  - [Membranous nephropathy].
AB  - Membranous nephropathy is characterized by immune complex deposits on the outer
      side of the glomerular basement membrane. Activation of complement and of
      oxidation lead to basement membrane lesions. The most frequent form is
      idiopathic. At 5 and 10 years, renal survival is around 90 and 65% respectively.
      A prognostic model based on proteinuria, level and duration, progression of renal
      failure in a few months can refine prognosis. The urinary excretion of C5b-9,
      beta2 and alpha1 microglobuline and IgG are strong predictors of outcome.
      Symptomatic treatment is based on anticoagulation in case of nephrotic syndrome,
      angiotensin conversion enzyme inhibitors, angiotensin II receptor blockers and
      statins. Immunosuppressive therapy should be discussed for patients having a high
      risk of progression. Corticoids alone has no indication. Treatment should include
      a simultaneous association or more often alternating corticoids and alkylant
      agent for a minimum of 6 months. Adrenocorticoid stimulating hormone and steroids
      plus mycophenolate mofetil may be equally effective. Steroids plus alkylant
      decrease the risk of end stage renal failure. Cyclosporine and tacrolimus
      decrease proteinuria but are associated with a high risk of recurrence at time of
      withdrawal and are nephrotoxic. Rituximab evaluated on open studies needs further
      evaluations to define its use. 

PMID- 24315536
TI  - Clinical, neuroimaging, and genetic characteristics of megalencephalic
      leukoencephalopathy with subcortical cysts in Egyptian patients.
AB  - BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a
      rare and genetically heterogeneous cerebral white matter disease. Clinically, it
      is characterized by macrocephaly, developmental delay, and seizures. We explore
      the clinical spectrum, neuroimaging characteristics, and gene involvement in the
      first patients with megalencephalic leukoencephalopathy with subcortical cysts
      described from Egypt. PATIENTS: Six patients were enrolled from three unrelated
      families. Patient inclusion criteria were macrocephaly, developmental delay,
      normal urinary organic acids, and brain imaging of diffuse cerebral white matter
      involvement. Direct sequencing of the MLC1 gene in patients' families and GliaCAM
      in one questionable case was performed using BigDye Terminator cycle sequencing.
      RESULTS: Clinical heterogeneity, both intra- and interfamilial, was clearly
      evident. Developmental delays ranged from globally severe or moderate to mild
      delay in achieving walking or speech. Head circumference above the ninety-seventh
      percentile was a constant feature. Neuroimaging featured variability in white
      matter involvement and subcortical cysts. However, findings of posterior fossa
      changes and brain stem atrophy were frequently (66.6%) identified in these
      Egyptian patients. Discrepancy between severe brain involvement and normal mental
      functions was evident, particularly in patients from the third family. MLC1
      mutations were confirmed in all patients. Deletion/insertion mutation in exon 11
      (c.908-918delinsGCA, p.Val303 Gly fsX96) was recurrent in two families, whereas a
      missense mutation in exon 10 (c.880 C > T, p.Pro294Ser) was identified in the
      third family. CONCLUSIONS: This report extends our knowledge of the clinical and
      neuroimaging features of megalencephalic leukoencephalopathy with subcortical
      cysts. It confirms the apparent lack of selective disadvantage of MLC1 mutations
      on gamete conception and transmission as supported by the presence of multiple
      affected siblings in Egyptian families.

PMID- 24315538
TI  - Anti-N-methyl-D-aspartate receptor-mediated encephalitis in infants and toddlers:
      case report and review of the literature.
AB  - BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly
      well-recognized inflammatory encephalitis in children and adults. PATIENT: We
      report a previously healthy 21-month-old girl who presented with behavioral
      change, self-mutilatory behavior, and echolalia. Over the ensuing weeks, symptoms
      progressed to include unilateral upper extremity dystonia, gait impairment,
      dysphagia, and mutism. Magnetic resonance imaging of the brain showed a tiny area
      of signal abnormality in the subcortical white matter, but was otherwise normal.
      Continuous video electroencephalography showed slowing of the background rhythm,
      but was without epileptiform discharges. Lumbar puncture showed a mild
      pleocytosis of mixed cellularity; bacterial culture and testing for various viral
      encephalitides were negative. Serum and cerebrospinal fluid was positive for
      autoantibodies directed against the N-methyl-D-aspartate receptor, and she was
      diagnosed with anti-N-methyl-D-aspartate receptor encephalitis. The patient was
      successfully treated with a regimen of immunotherapy that included dexamethasone,
      intravenous immunoglobulin, and rituximab. One year after initial presentation,
      the patient remained symptom-free. We further review the clinical
      characteristics, results of diagnostic studies, treatment, and outcome of infants
      and toddlers diagnosed with anti-N-methyl-D-aspartate receptor encephalitis that
      have been previously reported in the literature. CONCLUSION: Anti-N-methyl-D
      aspartate receptor encephalitis is relatively common among infants and toddlers
      and often presents with a pattern of defining characteristics in this age group,
      particularly the absence of associated tumor.

PMID- 24315539
TI  - Folinic acid responsive epilepsy in Ohtahara syndrome caused by STXBP1 mutation.
AB  - BACKGROUND: Ohtahara syndrome is a severe condition with early onset of recurrent
      unprovoked seizures associated with abnormal electroencephalography and global
      developmental delay. Folinic acid-responsive seizures are treatable causes of
      Ohtahara syndrome, which is thought to be due to recessive mutations in the
      ALDH7A1 gene, resulting in deficiency of antiquitin. METHOD: Here we report a
      girl with Ohtahara syndrome who exhibited transient folinic acid responsiveness
      but without evidence of antiquitin dysfunction. RESULTS: She was later found to
      have a known missense mutation (c.1439 C > T, p.P480 L) in exon 16 of the STXBP1
      gene. CONCLUSION: For infants presenting with Ohtahara syndrome with
      responsiveness to folinic acid and negative antiquitin deficiency analyses,
      genetic testing for other possible causative genes such as STXBP1 mutation is
      recommended.

PMID- 24315540
TI  - Response to Passos et al.

PMID- 24315541
TI  - Electrophysiological characteristics of the pediatric femoral nerve and their use
      in clinical diagnosis.
AB  - OBJECTIVE: To explore the electrophysiological characteristics of the pediatric
      femoral nerve at different ages. METHODS: Surface electrodes were used to detect
      femoral nerve conduction in 163 healthy children aged 0-14 years recruited to
      this study and divided into six age groups. Based on the range of normal values
      obtained, the diagnosis of 22 patients with suspected femoral nerve injury was
      confirmed. RESULTS: We obtained normal values for pediatric femoral nerve motor
      and sensory conduction in all age groups, including proximal and distal compound
      muscle action potential latencies, proximal compound muscle action potential
      amplitude and duration, motor conduction velocity, F-wave latency, and sensory
      conduction velocity. We measured proximal compound muscle action potential in all
      children in all age groups. The manifestation of femoral nerve injury in the 22
      patients was primarily a clear decrease or absence of compound muscle action
      potential amplitude or a lengthened latency. Electromyographs revealed that 104
      muscle parts were involved in the nerve function, in which 59 parts were found to
      be abnormal (56.73%). CONCLUSIONS: The development of pediatric femoral nerve
      mainly began after 1 years old and continued to 14 years old. The proximal
      latency and compound muscle action potential amplitude of the pediatric femoral
      nerve have clinical value. Detection of the femoral nerve is important in the
      diagnosis of lower limb monoplegia, especially for acute flaccid paralysis
      associated with nonpolio enterovirus infection.

PMID- 24315542
TI  - Delay in seeking medical evaluations and predictors of self-efficacy among women
      with newly diagnosed breast cancer: a longitudinal study.
AB  - BACKGROUND: Delaying a diagnosis of breast cancer directly and positively impacts
      survival. Self-efficacy has been shown to be a causal mechanism in a wide range
      of health behaviors, a measurable trait that predicts behavior across domains,
      which is strong associated with psychological variables. However, factors
      predicting self-efficacy of women with suspected breast cancer who delayed or did
      not delay seeking a breast cancer diagnosis over time have not been identified.
      OBJECTIVES: To examine the differences between women who delay and women who did
      not delay seeking a cancer diagnosis, and key factors predicting self-efficacy
      over time among women with newly-diagnosed breast cancer. DESIGN: Descriptive,
      longitudinal design over 2 months following breast cancer diagnostic evaluation.
      SETTING: A medical center is located in southern Taiwan. PARTICIPANTS: Eighty
      women with suspected breast cancer were approached and 67 subjects with a
      positive diagnosis of breast cancer were recruited. METHODS: Subjects were
      categorized into women who delayed their diagnosis and women who did not delay
      their diagnosis. A battery of 5 standardized questionnaires including self
      efficacy, anxiety and depression, personality, spiritual support and hope was
      completed at the first three clinic visits. RESULTS: Stage of cancer, trait
      extroversion/neuroticism and spiritual support were significantly different
      between groups (p<0.05). Subjects who did not delay (beta=-1.613, p<0.05), and
      time that histology results were provided (beta=-2.4333, p<0.001) had a
      significantly predicted negative change in self-efficacy compared to the group
      that delayed. Hope at the first clinic visit contributed to the change in self
      efficacy over time (beta=0.391, p<0.001). CONCLUSIONS: Personal factors affecting
      a woman's delay in obtaining medical assessment of breast cancer confirmation.
      Hope impacts self-efficacy of women with suspected breast cancer and
      interventions to enhance hope during the early stages of breast cancer evaluation
      require further study.

PMID- 24315543
TI  - Predictors of frequent visits to a psychiatric emergency room: a large-scale
      register study combined with a small-scale interview study.
AB  - BACKGROUND: The role of the psychiatric emergency services has undergone
      extensive changes following a significant downsizing of the number of psychiatric
      hospital beds during the past decades. A relatively small number of "frequent
      visitors" accounts for a disproportionately large amount of visits to psychiatric
      emergency services. OBJECTIVES: To identify predictors of frequent use of a
      psychiatric emergency room at a Danish University Psychiatric Hospital through a
      12-year period (1995-2007) and to speculate on how changes in the mental
      healthcare services affect predictors of frequent use through time. DESIGN: A
      large-scale register based logistic regression analysis combined with a small
      scale explorative, interpretative interview study. Register data were drawn from
      the Danish Central Psychiatric Research Register. Four-year cohorts (1995, 1998,
      2001 and 2004) of patients with at least one visit to the psychiatric emergency
      room were followed for 3 years to identify general trends of predictors
      throughout the period. A purposeful sample of 15 frequent visitors were
      interviewed about their personal motives for visiting the psychiatric emergency
      room, their pathways to care, and their social network and social support.
      RESULTS: The study identified two overall trends of predictors of frequent use of
      the psychiatric emergency room. High use of psychiatric services: >=5 visits to
      the psychiatric emergency room, >=3 admissions or >=60 bed days during the year,
      was and continued to be predictive of high use of the psychiatric emergency room
      throughout the whole period. Furthermore, the emergence and continual presence of
      the predictors: severe mental illness (1999-onwards), substance abuse (2002
      onwards) and sheltered housing (2002-2003-2005-onwards) indicated changes in the
      general profile of frequent visitors to the psychiatric emergency room, where
      predictors related to illness behaviour were supplemented by predictors related
      to disease. CONCLUSION: The changing profile of the conditions predicting
      frequent visits at the psychiatric emergency room was most probably related to
      the adverse effects of the continuous deinstitutionalising of the Danish mental
      health services and a radical health care reform. A basic multiplicative model
      was designed for the early detection of individual frequent visitors.

PMID- 24315544
TI  - Corticomuscular coherence in acute and chronic stroke.
AB  - OBJECTIVE: Motor recovery after stroke is attributed to neuronal plasticity,
      however not all post-stroke neuronal changes relate to regaining fine motor
      control. Corticomuscular coherence (CMC) is a measure allowing to trace neuronal
      reorganizations which are functionally relevant for motor recovery. Contrary to
      previous studies which were performed only in chronic stage, we measured CMC in
      patients with stroke at both acute and chronic stroke stages. METHODS: For the
      detection of CMC we used multichannel EEG and EMG recordings along with an
      optimization algorithm for the detection of corticomuscular interactions.
      RESULTS: In acute stroke, the CMC amplitude was larger on the unaffected side
      compared to the affected side and also larger compared to the unaffected side in
      the chronic period. Additionally, CMC peak frequencies on both sides decreased in
      the acute compared to the chronic period and to control subjects. In chronic
      stage, there were no inter-hemispheric or group differences in CMC amplitude or
      frequency. CONCLUSIONS: The changes in CMC parameters in acute stroke could
      result from a temporary decrease in inhibition, which normalizes in the course of
      recovery. As all patients showed very good motor recovery, the modulation of CMC
      amplitude and frequency over time might thus reflect the process of motor
      recovery. SIGNIFICANCE: We demonstrate for the first time the dynamical changes
      of corticomuscular interaction both at acute and chronic stage of stroke.

PMID- 24315546
TI  - Procalcitonin in the recognition of complications in critically ill surgical
      patients.
AB  - BACKGROUND: Procalcitonin (PCT) is a relatively new, promising indirect parameter
      for infection. In the intensive care unit (ICU) it can be used as a marker for
      sepsis. However, in the ICU there is a need for reliable markers for clinical
      deterioration in the critically ill patients. This study determines the clinical
      value of PCT concentrations in recognizing surgical complications in a
      heterogeneous group of general surgical patients in the ICU. MATERIAL AND
      METHODS: We prospectively collected PCT concentration data from April 2010 to
      June 2012 for all general surgical patients admitted to the ICU. Both the
      relationships between PCT levels and events (diagnostic and therapeutic
      interventions) as well as between PCT levels and surgical complications
      (abscesses, bleeding, perforation, ischemia, and ileus) were studied. RESULTS:
      PCT concentrations were lower in patients who developed complications than those
      who did not develop complications on the same day, although not significant (P =
      0.27). A 10% increase in PCT levels resulted in a 2% higher complication odds,
      but again this was not significant (odds ratio [OR], 1.020; 95% confidence
      interval [CI], 0.961-1.083; P = 0.51). Even a 20% or 30% increase in PCT
      concentrations did not result in higher complication probability (OR, 1.039; 95%
      CI, 0.927-1.165 and OR, 1.057; 95% CI, 0.897-1.246). Furthermore, an increase in
      PCT levels did not show an increase or a reduction in the number of diagnostic
      and therapeutic interventions. CONCLUSIONS: An increase in PCT levels does not
      help to predict surgical complications in critically ill surgical patients.

PMID- 24315545
TI  - Electrocorticographic correlates of overt articulation of 44 English phonemes:
      intracranial recording in children with focal epilepsy.
AB  - OBJECTIVE: We determined the temporal-spatial patterns of electrocorticography
      (ECoG) signal modulation during overt articulation of 44 American English
      phonemes. METHODS: We studied two children with focal epilepsy who underwent
      extraoperative ECoG recording. Using animation movies, we delineated 'when' and
      'where' gamma- (70-110 Hz) and low-frequency-band activities (10-30 Hz) were
      modulated during self-paced articulation. RESULTS: Regardless of the classes of
      phoneme articulated, gamma-augmentation initially involved a common site within
      the left inferior Rolandic area. Subsequently, gamma-augmentation and/or
      attenuation involved distinct sites within the left oral-sensorimotor area with a
      timing variable across phonemes. Finally, gamma-augmentation in a larynx
      sensorimotor area took place uniformly at the onset of sound generation, and
      effectively distinguished voiced and voiceless phonemes. Gamma-attenuation
      involved the left inferior-frontal and superior-temporal regions simultaneously
      during articulation. Low-frequency band attenuation involved widespread regions
      including the frontal, temporal, and parietal regions. CONCLUSIONS: Our
      preliminary results support the notion that articulation of distinct phonemes
      recruits specific sensorimotor activation and deactivation. Gamma attenuation in
      the left inferior-frontal and superior-temporal regions may reflect transient
      functional suppression in these cortical regions during automatic, self-paced
      vocalization of phonemes containing no semantic or syntactic information.
      SIGNIFICANCE: Further studies are warranted to determine if measurement of event
      related modulations of gamma-band activity, compared to that of the low-frequency
      band, is more useful for decoding the underlying articulatory functions.

PMID- 24315547
TI  - First trimester caesarean scar ectopic pregnancy evaluation using MRI.
AB  - AIM: To determine the features of caesarean scar ectopic pregnancy (CSP) by using
      magnetic resonance imaging (MRI) in the first trimester. MATERIALS AND METHODS:
      Thirty-nine women with CSP in the first trimester were initially selected and
      underwent transvaginal ultrasound and MRI examinations. Thirty-five patients with
      CSP were finally included in this study. RESULTS: The CSPs were categorized into
      three groups: type I, in which a thin-walled diverticulum is present at the
      caesarean section scar (CSS) defect and the gestational sac (GS) is embedded in
      the diverticulum; type II, in which a thin-walled diverticulum is present at the
      CSS defect and the GS is partially embedded in the diverticulum; type III, in
      which a niche is present in the CSS defect and the GS is mainly embedded in the
      isthmus. Types I, II, and III CSP occurred in 40, 46, and 14% of the women,
      respectively. There was no significant difference between the three types in the
      minimum thickness of the CSS defect. In types I and II, there was a positive
      correlation in the maximum inlet diameter of the CSS defect and the approximate
      area of the GS. CONCLUSION: Using MRI, most CSPs present as a diverticulum at the
      CSS defect, and the CSS defect becomes weaker with the growth of the GS. MRI
      showed detailed features of the CSP.

PMID- 24315548
TI  - Randomized clinical trial of cutting balloon angioplasty versus high-pressure
      balloon angioplasty in hemodialysis arteriovenous fistula stenoses resistant to
      conventional balloon angioplasty.
AB  - PURPOSE: To compare the efficacy and safety of cutting balloon angioplasty (CBA)
      versus high-pressure balloon angioplasty (HPBA) for the treatment of hemodialysis
      autogenous fistula stenoses resistant to conventional percutaneous transluminal
      angioplasty (PTA). MATERIALS AND METHODS: In a prospective, randomized clinical
      trial involving patients with dysfunctional, stenotic hemodialysis arteriovenous
      fistulas (AVFs), patients were randomized to receive CBA or HPBA if conventional
      PTA had suboptimal results (ie, residual stenosis > 30%). A total of 516 patients
      consented to participate in the study from October 2008 to September 2011, 85% of
      whom (n = 439) had technically successful conventional PTA. The remaining 71
      patients (mean age, 60 y; 49 men) with suboptimal PTA results were eventually
      randomized: 36 to the CBA arm and 35 to the HPBA arm. Primary and secondary
      target lesion patencies were determined by Kaplan-Meier analysis. RESULTS:
      Clinical success rates were 100% in both arms. Primary target lesion patency
      rates at 6 months were 66.4% and 39.9% for CBA and HPBA, respectively (P = .01).
      Secondary target lesion patency rates at 6 months were 96.5% for CBA and 80.0%
      for HPBA (P = .03). There was a single major complication of venous perforation
      following CBA. The 30-day mortality rate was 1.4%, with one non-procedure-related
      death in the HPBA group. CONCLUSIONS: Primary and secondary target lesion patency
      rates of CBA were statistically superior to those of HPBA following suboptimal
      conventional PTA. For AVF stenoses resistant to conventional PTA, CBA may be a
      better second-line treatment given its superior patency rates.

PMID- 24315549
TI  - Efficacy and safety of portal vein embolization for two-stage hepatectomy in
      patients with colorectal liver metastasis.
AB  - PURPOSE: To examine the efficacy and safety of portal vein embolization (PVE)
      when used during two-stage hepatectomy for bilobar colorectal liver metastases
      (CLM). MATERIALS AND METHODS: PVE was performed as an adjunct to two-stage
      hepatectomy in 56 patients with CLM. Absolute future liver remnant (FLR) volumes,
      standardized FLR ratios, degree of hypertrophy (DH), and complications were
      analyzed. Segment II and III volumes and DH were also measured separately. All
      volumetric measurements were compared with a cohort of 96 patients (n = 37 right
      portal vein embolization [RPVE], n = 59 right portal vein embolization extended
      to segment IV portal veins [RPVE+4]) in whom PVE was performed before single
      stage hepatectomy. RESULTS: For patients who completed RPVE during two-stage
      hepatectomy (n = 17 of 17), mean absolute FLR volume increased from 272.1 cm(3)
      to 427.0 cm(3) (P < .0001), mean standardized FLR ratio increased from 0.17 to
      0.26 (P < .0001), and mean DH was 0.094. For patients who completed RPVE+4 during
      two-stage hepatectomy (n = 38 of 39), mean FLR volume increased from 288.7 cm(3)
      to 424.8 cm(3) (P < .0001), mean standardized FLR increased from 0.18 to 0.26 (P
      < .0001), and mean DH was 0.083. DH of the FLR was not significantly different
      between two-stage hepatectomy and single-stage hepatectomy. Complications after
      PVE occurred in five (8.9%) patients undergoing two-stage hepatectomy.
      CONCLUSIONS: PVE effectively and safely induced a significant DH in the FLR
      during two-stage hepatectomy in patients with CLM.

PMID- 24315550
TI  - Mistargeting after fusion imaging-guided percutaneous radiofrequency ablation of
      hepatocellular carcinomas.
AB  - PURPOSE: To evaluate the incidence and causes of mistargeting after fusion
      imaging-guided percutaneous radiofrequency (RF) ablation of hepatocellular
      carcinomas (HCCs). MATERIALS AND METHODS: Between September 2011 and March 2013,
      955 HCCs in 732 patients were treated with percutaneous RF ablation. Among them,
      ablation of 551 HCCs was accomplished under fusion imaging guidance, and seven
      mistargetings were noted in seven patients (male-to-female ratio = 6:1; mean age,
      60.1 y; range, 47-73 y). The incidence of mistargeting and the cause of liver
      disease in the patients with mistargeting were evaluated. The causes of
      mistargeting were assessed according to the following classification: small size
      of HCC, subcapsular location, subphrenic location, confusion with pseudolesions,
      poor conspicuity of HCC, poor sonographic window, and poor electrode path.
      RESULTS: The incidence of mistargeting after fusion imaging-guided RF ablation
      was 1.3% (7 of 551). All patients with mistargeting were hepatitis B virus
      carriers. The most common cause of mistargeting was the small size of HCC (100%;
      7 of 7), followed by confusion with surrounding pseudolesions (85.7%; 6 of 7),
      subcapsular (71.4%; 5 of 7) and subphrenic locations (71.4%; 5 of 7), poor
      conspicuity of the HCC (71.4%; 6 of 7), poor sonographic window (28.6%; 2 of 7),
      and poor electrode path (28.6%; 2 of 7). CONCLUSIONS: The incidence of
      mistargeting after fusion imaging-guided RF ablation was 1.3%. The most common
      cause of mistargeting was the small size of HCC, followed by confusion with
      surrounding pseudolesions, subcapsular and subphrenic locations, and poor
      conspicuity of the HCC.

PMID- 24315551
TI  - Review of the efficacy of transcranial magnetic stimulation for auditory verbal
      hallucinations.
AB  - With an increase of the number of studies exploring repetitive transcranial
      magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations
      (AVH), an update is provided on the efficacy of different paradigms. A literature
      search was performed from 1966 through April 2013. Twenty-five randomized
      controlled trials using the severity of AVH or psychosis as outcome measures were
      included. Standardized mean weighted effect sizes were computed; a qualitative
      review of the literature was performed to assess the effects of various rTMS
      paradigms. rTMS versus sham treatment for AVH yielded a mean weighted effect size
      of .44. No significant mean weighted effect size was found for the severity of
      psychosis (i.e., .21). For patients with medication-resistant AVH, the mean
      weighted effect size was .45. rTMS applied at the left temporoparietal area with
      a frequency of 1 Hz yielded a moderate mean weighted effect size of .63,
      indicating superiority of this paradigm. Various other paradigms failed to show
      superior effects. rTMS applied at the right temporoparietal area was not superior
      to sham treatment. rTMS, especially when applied at the left temporoparietal area
      with a frequency of 1 Hz, is effective for the treatment of AVH, including in
      patients with medication-resistant AVH. The results for other rTMS paradigms are
      disappointing thus far. A next step should be to explore the effects of rTMS in
      medication-free individuals, for example, during the initial phases of psychosis,
      and in patients with diagnoses other than schizophrenia who do not have comorbid
      psychotic symptoms. 

PMID- 24315553
TI  - An LCA model for waste incineration enhanced with new technologies for metal
      recovery and application to the case of Switzerland.
AB  - A process model of municipal solid waste incinerators (MSWIs) and new
      technologies for metal recovery from combustion residues was developed. The
      environmental impact is modeled as a function of waste composition as well as
      waste treatment and material recovery technologies. The model includes combustion
      with a grate incinerator, several flue gas treatment technologies, electricity
      and steam production from waste heat recovery, metal recovery from slag and fly
      ash, and landfilling of residues and can be tailored to specific plants and sites
      (software tools can be downloaded free of charge). Application of the model to
      Switzerland shows that the treatment of one tonne of municipal solid waste
      results on average in 425 kg CO2-eq. generated in the incineration process, and
      54 kg CO2-eq. accrue in upstream processes such as waste transport and the
      production of operating materials. Downstream processes, i.e. residue disposal,
      generates 5 kg CO2-eq. Savings from energy recovery are in the range of 67 to 752
      kg CO2-eq. depending on the assumptions regarding the substituted energy
      production, while the recovery of metals from slag and fly ash currently results
      in a net saving of approximately 35 kg CO2-eq. A similar impact pattern is
      observed when assessing the MSWI model for aggregated environmental impacts
      (ReCiPe) and for non-renewable resource consumption (cumulative exergy demand),
      except that direct emissions have less and no relevance, respectively, on the
      total score. The study illustrates that MSWI plants can be an important element
      of industrial ecology as they provide waste disposal services and can help to
      close material and energetic cycles.

PMID- 24315552
TI  - Early stress prevents the potentiation of muscarinic excitation by calcium
      release in adult prefrontal cortex.
AB  - BACKGROUND: The experience of early stress contributes to the etiology of several
      psychiatric disorders and can lead to lasting deficits in working memory and
      attention. These executive functions require activation of the prefrontal cortex
      (PFC) by muscarinic M1 acetylcholine (ACh) receptors. Such Galphaq-protein
      coupled receptors trigger the release of calcium (Ca(2+)) from internal stores
      and elicit prolonged neuronal excitation. METHODS: In brain slices of rat PFC, we
      employed multiphoton imaging simultaneously with whole-cell electrophysiological
      recordings to examine potential interactions between ACh-induced Ca(2+) release
      and excitatory currents in adulthood, across postnatal development, and following
      the early stress of repeated maternal separation, a rodent model for depression.
      We also investigated developmental changes in related genes in these groups.
      RESULTS: Acetylcholine-induced Ca(2+) release potentiates ACh-elicited excitatory
      currents. In the healthy PFC, this potentiation of muscarinic excitation emerges
      in young adulthood, when executive function typically reaches maturity. However,
      the developmental consolidation of muscarinic ACh signaling is abolished in
      adults with a history of early stress, where ACh responses retain an adolescent
      phenotype. In prefrontal cortex, these rats show a disruption in the expression
      of multiple developmentally regulated genes associated with Galphaq and Ca(2+)
      signaling. Pharmacologic and ionic manipulations reveal that the enhancement of
      muscarinic excitation in the healthy adult PFC arises via the electrogenic
      process of sodium/Ca(2+) exchange. CONCLUSIONS: This work illustrates a long
      lasting disruption in ACh-mediated cortical excitation following early stress and
      raises the possibility that such cellular mechanisms may disrupt the maturation
      of executive function.

PMID- 24315554
TI  - Timing of surgical staging in adult spinal deformity surgery: is later better?
AB  - COMMENTARY ON: Hassanzadeh H, Gjolaj JP, El Dafrawy MH, et al. The timing of
      surgical staging has a significant impact on the complications and functional
      outcomes of adult spinal deformity surgery. Spine J 2013;13:1717-22 (in this
      issue).

PMID- 24315555
TI  - Stabilizing osteoporotic thoracolumbar fractures through an anterior or posterior
      approach: what works best?
AB  - COMMENTARY ON: Sudo H, Ito M, Kaneda K, et al. Anterior decompression and strut
      graft versus posterior decompression and pedicle screw fixation with
      vertebroplasty for osteoporotic thoracolumbar vertebral collapse with
      neurological deficits. Spine J 2013;13:1726-32 (in this issue).

PMID- 24315556
TI  - The spine surgery waiting place.
AB  - COMMENTARY ON: Quon JA, Sobolev BG, Levy AR, et al. The effect of waiting time on
      pain intensity after elective surgical lumbar discectomy. Spine J 2013;13:1736-48
      (in this issue).

PMID- 24315557
TI  - Pedicle screw accuracy and the ramifications of imperfect screw placement.
AB  - COMMENTARY ON: Oh HS, Kim JS, Lee SH, et al. Comparison between the accuracy of
      percutaneous and open pedicle screw fixations in lumbosacral fusion. Spine J
      2013;13:1751-7 (in this issue). Costa F, Villa T, Anasetti F, et al. Primary
      stability of pedicle screws depends on the screw positioning and alignment. Spine
      J 2013;13:1934-9 (in this issue).

PMID- 24315558
TI  - Analysis of the direct cost of surgery for four diagnostic categories of adult
      spinal deformity.
AB  - BACKGROUND CONTEXT: Existing literature on adult spinal deformity (ASD) offers
      little guidance regarding an evidence-based approach to care. To optimize the
      value of medical treatment, a thorough understanding of the cost of surgical
      treatment for ASD is required. PURPOSE: To evaluate four clinically and
      radiographically distinct groups of ASD and identify and compare the cost of
      surgical treatment among the groups. STUDY DESIGN/SETTING: Multicenter
      retrospective study of consecutive surgeries for ASD. PATIENT SAMPLE: Three
      hundred twenty-five consecutive ASD patients treated between 2008 and 2010.
      OUTCOME MEASURES: Cost data were collected from hospital administrative records
      on the direct costs (DCs) incurred for the episode of surgical care, excluding
      overhead. METHODS: Based on preoperative radiographs and history, patients were
      categorized into one of four diagnostic categories of deformity: primary
      idiopathic scoliosis (PIS), primary degenerative scoliosis (PDS), primary
      sagittal plane deformity (PSPD), and revision (R). Analysis of variance and
      generalized linear model regressions were used to analyze the DCs of surgery and
      to assess differences in costs across the four diagnostic categories considered.
      RESULTS: Significant differences were observed in DC of surgery for different
      categories of ASD, with surgical treatment for PDS the most expensive followed in
      decreasing order by PSPD, PIS, and R (p<.01). Results further revealed a
      significant positive relationship between age and DC (p<.01) and a significant
      positive relationship between length of stay and DC (p<.01). Among PIS patients,
      for every incremental increase in levels fused, the expected DC increased by
      $3,997 (p=.00). Fusion to pelvis also significantly increased the DC of surgery
      for patients aged 18 to 29 years (p<.01) and 30 to 59 years (p<.01) but not for
      60 years or more (p=.86). CONCLUSIONS: There is an increasing DC of surgery with
      increasing age, length of hospital stay, length of fusion, and fusions to the
      pelvis. Revision surgery is the least expensive surgery on average and should
      therefore not preclude its consideration from a pure cost perspective.

PMID- 24315559
TI  - Personality pathology and increased use of medical resources in later adulthood.
AB  - OBJECTIVES: Personality pathology is associated with many negative health
      outcomes in young adulthood, including overutilization of healthcare resources.
      It is unclear, however, what the relation between personality pathology and
      medical resource utilization is as individuals age and develop new physical
      health problems. DESIGN: The present study examined whether personality disorder
      (PD) features were related to greater medical resource utilization in a sample of
      1,630 community-dwelling participants, aged 55-64 years. PD features and health
      status were measured at baseline; medical resource utilization and new physical
      health problems were measured at four 6-month follow-up assessments. Multilevel
      modeling analyses tested associations between number of physical health problems
      and PD features in medical resource use over time. RESULTS: Greater number of
      physical health problems significantly predicted higher medical resource
      utilization. The results also showed that many PD features were related to higher
      reported medical resource utilization independent of health status and
      sociodemographic variables. Schizoid and schizotypal PD features were associated
      with less reported medical resource utilization. When all PDs were included in
      the model together, dependent, antisocial, histrionic, and narcissistic PD
      features remained predictive of higher medical resource utilization. CONCLUSIONS:
      Personality pathology remains a relevant predictor of greater medical resource
      utilization into later adulthood and should be considered an important risk
      factor when trying to determine ways to reduce costly overuse of healthcare
      resources among older adults.

PMID- 24315560
TI  - Dementia Services Mini-Screen: a simple method to identify patients and
      caregivers in need of enhanced dementia care services.
AB  - OBJECTIVE: Improving dementia care in health systems requires estimates of need
      in the population served. We explored whether dementia-specific service needs and
      gaps for patients and caregivers could be predicted by simple information readily
      captured in routine care settings. METHOD: Primary family caregivers (n = 215)
      rated their own current stress, challenging patient behaviors, and prior-year
      needs and gaps in 16 medical and psychosocial services. These were evaluated with
      other patient and caregiver characteristics in multivariate regressions to
      identify unique predictors of service needs and gaps. RESULTS: Caregiver stress
      and patient behavior problems together accounted for an average of 24% of the
      whole-sample variance in total needs and gaps. All other variables combined
      (comorbid chronic disease, dementia severity, age, caregiver relationship, and
      residence) accounted for a mean of 3%, with none yielding more than 4% in any
      equation. We combined stress and behavior problem indicators into a simple
      screen. In early/mild dementia dyads (n = 111) typical in primary care settings,
      the screen identified gaps in total (84%) and psychosocial (77%) care services
      for high stress/high behavior problem dyads vs. 25% and 23%, respectively, of low
      stress/low behavior problem dyads. Medical care gaps were dramatically higher in
      high stress/high behavior problem dyads (66%) than all others (12%). CONCLUSION:
      The Dementia Services Mini-Screen is a simple tool that could help clinicians and
      health systems rapidly identify dyads needing enhanced dementia care, track key
      patient and caregiver outcomes of interventions, and estimate population needs
      for new service development.

PMID- 24315561
TI  - The patterns of cognitive and functional impairment in amnestic and non-amnestic
      mild cognitive impairment in geriatric depression.
AB  - OBJECTIVES: Depressed older adults are at risk for the development of mild
      cognitive impairment (MCI), but few studies have characterized MCI subtypes in
      geriatric depression. The objective of this study was to identify the clinical
      patterns of MCI in late-life depression. DESIGN: Baseline demographic, clinical,
      and neuropsychological test data collected as part of a randomized antidepressant
      trial for geriatric depression. SETTING: UCLA-based outpatient clinic.
      PARTICIPANTS: One hundred thirty-eight older adults with major depression.
      MEASUREMENTS: A neuropsychological test battery and comprehensive evaluations of
      depression, apathy, quality of life, medical burden, and vascular risk factors.
      RESULTS: Seventy-one participants (51%) had MCI and 67 (49%) were cognitively
      normal. Of subjects with MCI, 14 (20%) had amnestic MCI and 57 (80%) had non
      amnestic MCI. Overall, patients with MCI had greater depression severity, poorer
      quality of life, and worse performance on the Mini-Mental State Exam than
      patients without MCI. Patients with non-amnestic MCI had significantly greater
      depression severity than patients without MCI. Across all subjects, depression
      severity correlated with impaired performance in language and visuospatial
      functioning. CONCLUSION: Our findings suggest that MCI is associated with greater
      severity of depression, poorer quality of life, and worse global cognitive
      function. Overall, subtypes of MCI in geriatric depression differ in the patterns
      of functional impairment, which may require different therapeutic approaches.

PMID- 24315562
TI  - Predictive treatment management: incorporating a predictive tumor response model
      into robust prospective treatment planning for non-small cell lung cancer.
AB  - PURPOSE: We hypothesized that a treatment planning technique that incorporates
      predicted lung tumor regression into optimization, predictive treatment planning
      (PTP), could allow dose escalation to the residual tumor while maintaining
      coverage of the initial target without increasing dose to surrounding organs at
      risk (OARs). METHODS AND MATERIALS: We created a model to estimate the geometric
      presence of residual tumors after radiation therapy using planning computed
      tomography (CT) and weekly cone beam CT scans of 5 lung cancer patients. For
      planning purposes, we modeled the dynamic process of tumor shrinkage by morphing
      the original planning target volume (PTVorig) in 3 equispaced steps to the
      predicted residue (PTVpred). Patients were treated with a uniform prescription
      dose to PTVorig. By contrast, PTP optimization started with the same prescription
      dose to PTVorig but linearly increased the dose at each step, until reaching the
      highest dose achievable to PTVpred consistent with OAR limits. This method is
      compared with midcourse adaptive replanning. RESULTS: Initial parenchymal gross
      tumor volume (GTV) ranged from 3.6 to 186.5 cm(3). On average, the primary GTV
      and PTV decreased by 39% and 27%, respectively, at the end of treatment. The PTP
      approach gave PTVorig at least the prescription dose, and it increased the mean
      dose of the true residual tumor by an average of 6.0 Gy above the adaptive
      approach. CONCLUSIONS: PTP, incorporating a tumor regression model from the
      start, represents a new approach to increase tumor dose without increasing
      toxicities, and reduce clinical workload compared with the adaptive approach,
      although model verification using per-patient midcourse imaging would be prudent.

PMID- 24315564
TI  - New technique for developing a proton range compensator with use of a 3
      dimensional printer.
AB  - PURPOSE: A new system for manufacturing a proton range compensator (RC) was
      developed by using a 3-dimensional printer (3DP). The physical accuracy and
      dosimetric characteristics of the new RC manufactured by 3DP (RC_3DP) were
      compared with those of a conventional RC (RC_CMM) manufactured by a computerized
      milling machine (CMM). METHODS AND MATERIALS: An RC for brain tumor treatment
      with a scattered proton beam was calculated with a treatment planning system, and
      the resulting data were converted into a new format for 3DP using in-house
      software. The RC_3DP was printed with ultraviolet curable acrylic plastic, and an
      RC_CMM was milled into polymethylmethacrylate using a CMM. The inner shape of
      both RCs was scanned by using a 3D scanner and compared with TPS data by applying
      composite analysis (CA; with 1-mm depth difference and 1 mm distance-to-agreement
      criteria) to verify their geometric accuracy. The position and distal penumbra of
      distal dose falloff at the central axis and field width of the dose profile at
      the midline depth of spread-out Bragg peak were measured for the 2 RCs to
      evaluate their dosimetric characteristics. Both RCs were imaged on a computed
      tomography scanner to evaluate uniformity of internal density. The manufacturing
      times for both RCs were compared to evaluate the production efficiency. RESULTS:
      The pass rates for the CA test were 99.5% and 92.5% for RC_3DP and RC_CMM,
      respectively. There was no significant difference in dosimetric characteristics
      and uniformity of internal density between the 2 RCs. The net fabrication times
      of RC_3DP and RC_CMM were about 18 and 3 hours, respectively. CONCLUSIONS: The
      physical accuracy and dosimetric characteristics of RC_3DP were comparable with
      those of the conventional RC_CMM, and significant system minimization was
      provided.

PMID- 24315563
TI  - Preoperative radiation therapy with concurrent capecitabine, bevacizumab, and
      erlotinib for rectal cancer: a phase 1 trial.
AB  - PURPOSE: The goal of this phase 1 trial was to determine the maximum tolerated
      dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with
      preoperative radiation therapy for rectal cancer. METHODS AND MATERIALS: Patients
      with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal
      verge, were treated in 4 escalating dose levels, using the continual reassessment
      method. Patients received preoperative radiation therapy with concurrent
      bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine.
      Capecitabine dose was increased from 650 mg/m(2) to 825 mg/m(2) orally twice
      daily on the days of radiation therapy; erlotinib dose was increased from 50 mg
      orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in
      weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of
      bevacizumab. RESULTS: A total of 19 patients were enrolled, and 18 patients were
      considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had
      grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable
      patients underwent surgery, with low anterior resection in 7 (39%), proctectomy
      with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1
      (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had
      pathologic complete response, and 1 had complete response of the primary tumor
      with positive nodes. Three patients (17%) had grade 3 postoperative complications
      (ileus, small bowel obstruction, and infection). With a median follow-up of 34
      months, 1 patient developed distant metastasis, and no patient had local
      recurrence or died. The 3-year disease-free survival was 94%. CONCLUSIONS: The
      combination of preoperative radiation therapy with concurrent capecitabine,
      bevacizumab, and erlotinib was well tolerated. The pathologic complete response
      rate appears promising and may warrant further investigation.

PMID- 24315565
TI  - Mobilization of viable tumor cells into the circulation during radiation therapy.
AB  - PURPOSE: To determine whether radiation therapy (RT) could mobilize viable tumor
      cells into the circulation of non-small cell lung cancer (NSCLC) patients.
      METHODS AND MATERIALS: We enumerated circulating tumor cells (CTCs) by
      fluorescence microscopy of blood samples immunostained with conventional CTC
      markers. We measured their DNA damage levels using gamma-H2AX, a biomarker for
      radiation-induced DNA double-strand breaks, either by fluorescence-activated cell
      sorting or by immunofluorescence microscopy. RESULTS: Twenty-seven RT-treated
      NSCLC patients had blood samples analyzed by 1 or more methods. We identified
      increased CTC numbers after commencement of RT in 7 of 9 patients treated with
      palliative RT, and in 4 of 8 patients treated with curative-intent RT.
      Circulating tumor cells were also identified, singly and in clumps in large
      numbers, during RT by cytopathologic examination (in all 5 cases studied).
      Elevated gamma-H2AX signal in post-RT blood samples signified the presence of
      CTCs derived from irradiated tumors. Blood taken after the commencement of RT
      contained tumor cells that proliferated extensively in vitro (in all 6 cases
      studied). Circulating tumor cells formed gamma-H2AX foci in response to ex vivo
      irradiation, providing further evidence of their viability. CONCLUSIONS: Our
      findings provide a rationale for the development of strategies to reduce the
      concentration of viable CTCs by modulating RT fractionation or by coadministering
      systemic therapies.

PMID- 24315567
TI  - Cellular internalization of fibroblast growth factor-12 exerts radioprotective
      effects on intestinal radiation damage independently of FGFR signaling.
AB  - PURPOSE: Several fibroblast growth factors (FGFs) were shown to inhibit radiation
      induced tissue damage through FGF receptor (FGFR) signaling; however, this
      signaling was also found to be involved in the pathogenesis of several malignant
      tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be
      internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M,
      CPP-C). Therefore, this study focused on clarifying the role of FGF12
      internalization in protection against radiation-induced intestinal injury.
      METHODS AND MATERIALS: Each FGF or peptide was administered intraperitoneally to
      BALB/c mice in the absence of heparin 24 hours before or after total body
      irradiation with gamma rays at 9 to 12 Gy. Several radioprotective effects were
      examined in the jejunum. RESULTS: Administration of FGF12 after radiation
      exposure was as effective as pretreatment in significantly promoting intestinal
      regeneration, proliferation of crypt cells, and epithelial differentiation. Two
      domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were
      identified as being responsible for the radioprotective activity, so that
      deletion of both domains from FGF12B resulted in a reduction in activity.
      Interestingly, these regions included the CPP-M and CPP-C domains, respectively;
      however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1,
      prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP
      C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular
      internalization and increased radioprotective activity. However, FGF1/CPP-C
      reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying
      that FGFR signaling might not be essential for promoting the radioprotective
      effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation
      of p38alpha after irradiation, resulting in reduced radiation-induced apoptosis.
      CONCLUSIONS: These findings indicate that FGF12 can protect the intestine against
      radiation-induced injury through its internalization, independently of FGFRs,
      suggesting that cellular uptake of FGF12 is an alternative signaling pathway
      useful for cancer radiation therapy.

PMID- 24315568
TI  - Fertility after breast cancer treatment.
AB  - In many countries of the developed world, there is an increasing trend toward
      delay in childbearing from 30 to 40 years of age for various reasons. This is
      unfortunately concordant with an increasing incidence of breast cancer in women
      who have not yet completed their family. The current choice for premenopausal
      women with breast cancer is adjuvant therapy which includes cytotoxic
      chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian
      suppression), anti-estrogen therapy, or any combination of these. Although the
      use of adjuvant therapies with cytotoxic drugs can significantly reduce
      mortality, it raises issues of the long-term toxicity, such as induction of an
      early menopause and fertility impairment. The risk of infertility is a potential
      hardship to be faced by the patients following treatment of breast cancer. The
      offspring of patients who became pregnant after completion of chemotherapy have
      shown no adverse effects and congenital anomalies from the treatment, but
      sometimes high rates of abortion (29%) and premature deliveries with low birth
      weight (40%) have been demonstrated. Therefore, the issue of recent cytotoxic
      treatment remains controversial and further research is required to define a
      "safety period" between cessation of treatment and pregnancy. Preservation of
      fertility in breast cancer survivors of reproductive age has become an important
      issue regarding the quality of life. Currently, there are several potential
      options, including all available assisted technologies, such as in vitro
      fertilization and embryo transfer, in vitro maturation, oocyte and embryo
      cryopreservation, and cryopreservation of ovarian tissue. Because increased
      estrogen levels are thought to be potentially risky in breast cancer patients,
      recently developed ovarian stimulation protocols with the aromatase inhibitor
      letrozole and tamoxifen appear to provide safe stimulation with endogenous
      estrogen. Embryo cryopreservation seems to be the most established fertility
      preservation strategy, providing a 25-35% chance of pregnancy. In addition,
      oocyte freezing can be considered as an alternative in patients who are single
      and in those who do not wish a sperm donor. Although ovarian tissue harvesting
      appears to be safe, experience regarding ovarian transplantation is still limited
      due to low utilization, so the true value of this procedure remains to be
      determined. Nevertheless, in clinical situations in which chemotherapy needs to
      be started in young patients facing premature ovarian failure, ovarian tissue
      preservation seems to be a promising option for restoring fertility, especially
      in conjunction with other options like immature oocyte retrieval, in vitro
      maturation of oocytes, oocyte vitrification, or embryo cryopreservation. It seems
      that in vitro maturation is a useful strategy because it improves oocyte or
      cryopreservation outcome in breast cancer patients undergoing ovarian stimulation
      for fertility preservation. 

PMID- 24315566
TI  - A nonhuman primate model of human radiation-induced venocclusive liver disease
      and hepatocyte injury.
AB  - BACKGROUND: Human liver has an unusual sensitivity to radiation that limits its
      use in cancer therapy or in preconditioning for hepatocyte transplantation.
      Because the characteristic veno-occlusive lesions of radiation-induced liver
      disease do not occur in rodents, there has been no experimental model to
      investigate the limits of safe radiation therapy or explore the pathogenesis of
      hepatic veno-occlusive disease. METHODS AND MATERIALS: We performed a dose
      escalation study in a primate, the cynomolgus monkey, using hypofractionated
      stereotactic body radiotherapy in 13 animals. RESULTS: At doses >=40 Gy, animals
      developed a systemic syndrome resembling human radiation-induced liver disease,
      consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite,
      ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe
      disease that required euthanasia approximately 10 weeks after radiation. Even at
      lower doses in which radiation-induced liver disease was mild or nonexistent,
      latent and significant injury to hepatocytes was demonstrated by
      asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic
      failure with encephalopathy when they received parenteral nutrition containing
      high concentrations of glucose. Histologically, livers showed central obstruction
      via an unusual intimal swelling that progressed to central fibrosis. CONCLUSIONS:
      The cynomolgus monkey, as the first animal model of human veno-occlusive
      radiation-induced liver disease, provides a resource for characterizing the early
      changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic
      dosages, and for examining experimental therapies to minimize radiation injury.

PMID- 24315569
TI  - Bacterial infection (BI)-INDEX: an improved and simplified rapid flow cytometric
      bacterial infection marker.
AB  - The aim of this study was to develop a rapid and simple flow cytometric bacterial
      infection marker. In this prospective comparative study, quantitative flow
      cytometric analysis of CD10, CD35, CD66b, CD282, and MHC Class I molecules on
      human neutrophils, monocytes, and B-lymphocytes from 141 hospitalized febrile
      patients with suspected infection and from 50 healthy controls was performed. We
      developed a flow cytometric marker of local and systemic bacterial infections,
      designated "bacterial infection (BI)-INDEX", incorporating the quantitative
      analysis of CD10, CD35, MHCI, CD66b, and CD282 on neutrophils, monocytes, and B
      lymphocytes, which displayed 90% sensitivity and 96% specificity in
      distinguishing between microbiologically confirmed bacterial (n = 31) and viral
      infections (n = 27) within a 1-h time-frame. We propose that our novel rapid BI
      INDEX test will be useful in assisting physicians to ascertain whether antibiotic
      treatment is required, thus limiting unnecessary antimicrobial usage. 

PMID- 24315570
TI  - DSM-5 cannabis use disorder: a phenotypic and genomic perspective.
AB  - BACKGROUND: We explore the factor structure of DSM-5 cannabis use disorders,
      examine its prevalence across European- and African-American respondents as well
      as its genetic underpinnings, utilizing data from a genome-wide study of single
      nucleotide polymorphisms (SNPs). We also estimate the heritability of DSM-5
      cannabis use disorders explained by these common SNPs. METHODS: Data on 3053
      subjects reporting a lifetime history of cannabis use were utilized. Exploratory
      and confirmatory factor analyses were conducted to create a factor score, which
      was used in a genome-wide association analysis. p-values from the single SNP
      analysis were examined for evidence of gene-based association. The aggregate
      effect of all SNPs was also estimated using Genome-Wide Complex Traits Analysis.
      RESULTS: The unidimensionality of DSM-5 cannabis use disorder criteria was
      demonstrated. Comparing DSM-IV to DSM-5, a decrease in prevalence of cannabis use
      disorders was only noted in European-American respondents and was exceedingly
      modest. For the DSM-5 cannabis use disorders factor score, no SNP surpassed the
      genome-wide significance testing threshold. However, in the European-American
      subsample, gene-based association testing resulted in significant associations in
      3 genes (C17orf58, BPTF and PPM1D) on chromosome 17q24. In aggregate, 21% of the
      variance in DSM-5 cannabis use disorders was explained by the genome-wide SNPs;
      however, this estimate was not statistically significant. CONCLUSIONS: DSM-5
      cannabis use disorder represents a unidimensional construct, the prevalence of
      which is only modestly elevated above the DSM-IV version. Considerably larger
      sample sizes will be required to identify individual SNPs associated with
      cannabis use disorders and unequivocally establish its polygenic underpinnings.

PMID- 24315571
TI  - Suicide and substance use among female veterans: a need for research.
AB  - BACKGROUND: The number of female veterans is increasing. Veterans Administration
      (VA) enrollment increased over 40% from past eras. However, little research has
      focused on their mental health. We reviewed literature to examine associations of
      substance use with suicide in female veterans, identify research gaps, and inform
      future studies. METHODS: Google Scholar, Pub Med, and PsychINFO were searched
      using: substance use, female veteran, and suicide. Exclusion criteria (e.g., not
      discussing U.S. veterans) left 17 articles. RESULTS: Nine studies examined
      completed suicide among veterans. In most recent years, rates of deaths were
      greater for veterans than nonveterans, including females. Completed suicide was
      associated with past trauma, young age, and a mental disorder. Studies have often
      not addressed substance use. Three studies examined completed suicide among VA
      treated veterans without examining substance use as an associated factor. Rates
      of completed suicides were also higher among veterans than nonveterans, including
      females. A large proportion of females also had a mental diagnosis. Five studies
      examined substance use and attempted or completed suicide among VA treated
      veterans. Veterans in poor mental health had increased odds of suicide mortality;
      women with a substance use disorder (SUD) had a higher hazard ratio for completed
      suicide than men with a SUD. Engagement in substance abuse treatment decreased
      odds of suicide attempt among veterans. CONCLUSION: Available data suggest that
      suicide rates are higher among female veterans than women in the general
      population. Substance use may increase the likelihood of suicidal behaviors among
      female veterans, particularly those with a mental diagnosis.

PMID- 24315572
TI  - Abstinence-related changes in sleep during treatment for cocaine dependence.
AB  - BACKGROUND: Former sleep studies among non-treatment seeking chronic cocaine
      users had captured polysomnographic changes for as long as three weeks of
      abstinence. METHODS: 20 cocaine dependent participants, randomized to placebo in
      an ongoing clinical trial, received 12 days of inpatient substance abuse
      treatment followed by 6 weeks of outpatient cognitive behavioral therapy.
      Polysomnographic recording was performed on consecutive nights during the 1st and
      2nd inpatient and 3rd and 6th outpatient weeks. Number of days abstinent was
      determined from thrice weekly urine toxicology and self-report. Polysomnographic
      sleep was compared between study week 1 and 2, using paired t-tests. Trajectory
      of total sleep time (TST) was modeled both as a linear and a quadratic function
      of days abstinent. RESULTS: Despite reporting an improvement in overall sleep
      quality, polysomnographic sleep worsened from week 1 to 2. Among all
      participants, TST and stage 2 sleep time decreased, while REM sleep latency
      increased. Among participants who began the study with a positive urine test,
      there was also a decrease in REM and a trend for decreased slow wave sleep. TST
      compared to number of days abstinent (up to 54 days) was best fit with a
      quadratic model (p=0.002), suggesting the possibility of an improvement in total
      sleep time with extended abstinence. CONCLUSIONS: This is the first
      polysomnographic characterization of sleep in a large sample of cocaine users in
      treatment. Present findings confirm earlier results of poor and deteriorating
      sleep early in abstinence, and raise the possibility of improvement after an
      extended abstinence.

PMID- 24315573
TI  - Association of polymorphisms in iNOS and NQO1 with bladder cancer risk in
      cigarette smokers.
AB  - BACKGROUND:  NAD(P)H: quinine oxidoreductase (NQO1) plays an important role in
      the metabolism of several carcinogens contained in cigarettes. Inducible nitric
      oxide synthase (iNOS) expression had been detected in urinary bladder tumors. The
      aim of this study was to investigate the interaction of iNOS and NQO1 on bladder
      cancer (BC) risk stratified by cigarette smoking status. METHODS: A total of 159
      BC patients and 150 cancer-free controls were recruited from December 2003 to
      November 2004. Genotyping of NQO1 rs1800566 polymorphism and iNOS (CCTTT)n
      pentanucleotide repeat polymorphism was determined using the polymerase chain
      reaction-restricted fragment length polymorphism and sequencing method. The odds
      ratio and 95% confidence interval (CI) were calculated as a measure of the joint
      effect of NQO1 rs1800566 and iNOS (CCTTT)n polymorphisms on BC risk among
      cigarette smokers. RESULTS: Compared with study participants carrying the C/C
      genotype of NQO1 gene, those with C/T and T/T genotypes had a significantly
      increased BC risk of 1.8 (95% CI = 1.1-2.9). Among cigarette smokers, those who
      carried the 12-repeat allele of iNOS (CCTTT)n polymorphism had a significantly
      increased BC risk of 2.7 (95% CI = 1.0-6.7). Furthermore, a significant combined
      effect of the C/T and T/T genotypes of NQO1gene and the 12-repeat allele of iNOS
      (CCTTT)n repeat polymorphism on BC was found among cigarette smokers (odds ratio
      = 4.4, 95% CI = 1.3-14.9). CONCLUSION: Our findings suggest that a significant
      combined effect of NQO1 C/T and T/T genotypes and the 12-repeat allele of iNOS
      (CCTTT)n polymorphism on BC exists, especially in those with the habit of
      cigarette smoking.

PMID- 24315574
TI  - Antibiofilm activity of a monolayer of silver nanoparticles anchored to an amino
      silanized glass surface.
AB  - Biofilm production is the crucial pathogenic mechanism of the implant-associated
      infection and a primary target for new anti-infective strategies. Silver
      nanoparticles (AgNPs) are attracting interest for their multifaceted potential
      biomedical applications. As endowed with highest surface/mass ratio and potent
      antibacterial activity, they can profitably be applied as monolayers at
      biomaterial surfaces. Desirably, in order to minimize the risks of toxic effects
      from freely circulating detached nanoparticles, AgNPs should firmly be anchored
      to the modified biomaterial surfaces. Here we focus on a newly designed glass
      surface modified with AgNPs and on its antibiofilm properties. Link of a self
      assembled monolayer of AgNPs to glass was obtained through preliminary amino
      silanization of the glass followed by immersion in an AgNPs colloidal suspension.
      Static contact angle measure, AFM, TEM, UV-Vis spectroscopy, ICP atomic emission
      spectroscopy were used for characterization. Antibiofilm activity against the
      biofilm-producer Staphylococcus epidermidis RP62A was assayed by both CFU method
      and CLSM. Performances of AgNPs-glasses were: i) excellent stability in aqueous
      medium; ii) prolonged release and high local concentration of Ag(+) without any
      detaching of AgNPs; iii) strong antibiofilm activity against S. epidermidis
      RP62A. This AgNPs surface-modification can be applied to a large variety of
      biomaterials by simply depositing glass-like SiO2 films on their surfaces.

PMID- 24315575
TI  - Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic
      and imaging agents into brain tissues.
AB  - The effective protection of the blood-brain barrier (BBB) from tight junctions
      and efflux transport systems ultimately results in the limited entry of 95% of
      drug/gene candidates, which are potentially beneficial for central nervous system
      (CNS) diseases. In order to enhance the brain-specific delivery, in this study we
      developed a targeting carrier system, which consists of poly(carboxyl ethylene
      glycol-g-glutamate)-co-poly(distearin-g-glutamate) (CPEGGM-PDSGM) polymersomes
      with the conjugation of des-octanoyl ghrelin. Des-octanoyl ghrelin across the BBB
      was reported to be unidirectional (blood-to-brain direction). However, there is
      no report about the conjugation of des-octanoyl ghrelin to a drug carrier system
      to confer the BBB targeting property through des-octanoyl ghrelin binding sites
      mediated endocytosis. To qualitatively and quantitatively investigate this
      carrier's properties, coumarin 6, Cy5.5 and met-enkephalin were individually
      encapsulated in these polymersomes. The experimental results showed that the
      cellular uptake was significantly higher for des-octanoyl ghrelin-conjugated
      polymersomes (GPs) than unconjugated polymersomes when co-incubated with the BBB
      cells. In addition, an enhanced accumulation in brain together with a reduced
      accumulation in liver and spleen was observed in animal study, indicating better
      brain selectivity for the GPs. In a hot-plate test, a significant inhibition of
      nociceptive response could be achieved for an intravenous injection of GPs
      encapsulated with met-enkephalin. The overall results demonstrated that GPs own a
      great potential for targeting delivery of drug across the BBB to treat CNS
      diseases. 

PMID- 24315576
TI  - Neo-innervation of a bioengineered intestinal smooth muscle construct around
      chitosan scaffold.
AB  - Neuromuscular disorders of the gut result in disturbances in gastrointestinal
      transit. The objective of this study was to evaluate the neo-innervation of
      smooth muscle in an attempt to restore lost innervation. We have previously shown
      the potential use of composite chitosan scaffolds as support for intestinal
      smooth muscle constructs. However, the constructs lacked neuronal component.
      Here, we bioengineered innervated colonic smooth muscle constructs using rabbit
      colon smooth muscle and enteric neural progenitor cells. We also bioengineered
      smooth muscle only tissue constructs using colonic smooth muscle cells. The
      constructs were placed next to each other around tubular chitosan scaffolds and
      left in culture. Real time force generation conducted on the intrinsically
      innervated smooth muscle constructs showed differentiated functional neurons. The
      bioengineered smooth muscle only constructs became neo-innervated. The neo
      innervation results were confirmed by immunostaining assays. Chitosan supported
      (1) the differentiation of neural progenitor cells in the constructs and (2) the
      neo-innervation of non-innervated smooth muscle around the same scaffold. 

PMID- 24315577
TI  - Core-shell type lipid/rPAA-Chol polymer hybrid nanoparticles for in vivo siRNA
      delivery.
AB  - Our previous study had reported that cholesterol-grafted poly(amidoamine) (rPAA
      Chol polymer) was able to self-assemble into cationic nanoparticles and act as a
      potential carrier for siRNA transfection. In this study, the core-shell type
      lipid/rPAA-Chol hybrid nanoparticles (PEG-LP/siRNA NPs and T7-LP/siRNA NPs) were
      developed for improving in vivo siRNA delivery by modifying the surface of rPAA
      Chol/siRNA nanoplex core with a lipid shell, followed by post-insertion of
      polyethylene glycol phospholipid (DSPE-PEG) and/or peptide (HAIYPRH, named as T7)
      modified DSPE-PEG-T7. The integrative hybrid nanostructures of LP/siRNA NPs were
      evidenced by dynamic light scattering (DLS), confocal laser scanning microscope
      (CLSM), cryo-transmission electron microscope (Cryo-TEM) and surface plasmon
      resonance (SPR) assay. It was demonstrated that the T7 peptide modified LP/siRNA
      NPs (T7-LP/siRNA NPs) exhibited uniform and spherical structures with particle
      size of 99.39 +/- 0.65 nm and surface potential of 42.53 +/- 1.03 mV, and showed
      high cellular uptake efficiency and rapid endosomal/lysosomal escape ability in
      MCF-7 cells. Importantly, in vitro gene silencing experiment demonstrated that
      both of pegylated and targeted LP/siEGFR NPs exhibited significantly stronger
      downregulation of EGFR protein expression level in MCF-7 cells, compared to that
      of the physical mixture of siRNA lipoplexes and rPAA-Chol/siRNA nanoplexes. In
      vivo tumor therapy on nude mice bearing MCF-7 tumors further confirmed that the
      targeted T7-LP/siEGFR NPs exhibited the greatest inhibition on tumor growth via
      transferrin receptor-mediated targeting delivery, without any activation of
      immune responses and significant body weight loss following systemic
      administration. These findings indicated that the core-shell type T7-LP/siRNA
      nanoparticles would be promising siRNA delivery systems for in vivo tumor
      targeted therapy.

PMID- 24315579
TI  - Assessment of cognitive impairment in amyotrophic lateral sclerosis.

PMID- 24315578
TI  - The effect of autophagy inhibitors on drug delivery using biodegradable polymer
      nanoparticles in cancer treatment.
AB  - Nanoparticles of biodegradable polymers (NPs) have been widely used for drug
      delivery. However, there has been little research on their fate after
      internalized into the cells. We show in this research by using docetaxel as a
      model anticancer drug, which is formulated in the cholic acid conjugated
      nanoparticles of poly(lactic-co-glycolic acid (PLGA NPs) that the NPs induce
      autophagy of the cancer cells and thus may hinder the advantages of the
      nanomedicine. Moreover, we show both in vitro and in vivo that co-administration
      of autophagy inhibitors such as 3-methyladenine (3-MA) and Chloroquine (CQ) could
      greatly enhance the therapeutic effects of the nanoparticle formulation. The IC50
      values of the drug formulated in the PLGA NPs after 24 h treatment with no
      autophagy inhibitor or in combination with 10 mm 3-MA or 30 MUm CQ are 38.27 +/-
      1.23, 6.7 +/- 1.05, 4.78 +/- 1.75 MUg/mL, which implie 5.7 or 8,0 fold efficient
      by the autophagy inhibition respectively. Moreover, both the volume and the
      weight of the shrunk tumor of the mice after 20 day treatment with the PLGA NPs
      formulation combined with 3-MA or CQ are found to be only about a half in
      comparison with the treatment with the PLGA NPs formulation alone. In this
      research, we reported such a new mechanism of cancer cells to have PLGA NPs
      captured and degraded by auto-lysosomes. The findings provide advanced knowledge
      for development of nanomedicine for clinical application.

PMID- 24315580
TI  - Motor-dominant polyneuropathy due to IgM monoclonal antibody against disialosyl
      gangliosides in a patient with mantle cell lymphoma.
AB  - A rapidly progressive motor-dominant neuropathy associated with IgM monoclonal
      antibody against gangliosides with disialosyl residues, GD3, GD1b, GT1b, and
      GQ1b, in a 60-year-old Japanese man with mantle cell lymphoma is reported. Plasma
      exchange and chemotherapy for mantle cell lymphoma were performed for the
      neuropathy and mantle cell lymphoma. After therapy, the motor neuropathy
      dramatically improved concurrently with substantial reduction of the antibody
      activities especially in reaction to GD1b. This is the first case report of
      neuropathy with anti-disialosyl IgM antibodies associated with mantle cell
      lymphoma, and plasma exchange and chemotherapy were effective. 

PMID- 24315581
TI  - Cerebrolysin reduces amyloid-beta deposits, apoptosis and autophagy in the
      thalamus and improves functional recovery after cortical infarction.
AB  - Focal cerebral infarction causes amyloid-beta (Abeta) deposits and secondary
      thalamic neuronal degeneration. The present study aimed to determine the
      protective effects of Cerebrolysin on Abeta deposits and secondary neuronal
      damage in thalamus after cerebral infarction. At 24h after distal middle cerebral
      artery occlusion (MCAO), Cerebrolysin (5 ml/kg) or saline as control was once
      daily administered for consecutive 13 days by intraperitoneal injection. Sensory
      function and secondary thalamic damage were assessed with adhesive-removal test,
      Nissl staining and immunofluorescence at 14 days after MCAO. Abeta deposits,
      activity of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1),
      apoptosis and autophagy were determined by TUNEL staining, immunofluorescence and
      immunoblot. The results showed that Cerebrolysin significantly improved sensory
      deficit compared to controls (p<0.05). Abeta deposits and BACE1 were obviously
      reduced by Cerebrolysin, which was accompanied by decreases in neuronal loss and
      astroglial activation compared to controls (all p < 0.05). Coincidently,
      Cerebrolysin markedly inhibited cleaved caspase-3, conversion of LC3-II,
      downregulation of Bcl-2 and upregulation of Bax in the ipsilateral thalamus
      compared to controls (all p<0.05). These findings suggest that Cerebrolysin
      reduces Abeta deposits, apoptosis and autophagy in the ipsilateral thalamus,
      which may be associated with amelioration of secondary thalamic damage and
      functional recovery after cerebral infarction.

PMID- 24315582
TI  - Familial searching: a specialist forensic DNA profiling service utilising the
      National DNA Database to identify unknown offenders via their relatives--the UK
      experience.
AB  - The National DNA Database (NDNAD) of England and Wales was established on April
      10th 1995. The NDNAD is governed by a variety of legislative instruments that
      mean that DNA samples can be taken if an individual is arrested and detained in a
      police station. The biological samples and the DNA profiles derived from them can
      be used for purposes related to the prevention and detection of crime, the
      investigation of an offence and for the conduct of a prosecution. Following the
      South East Asian Tsunami of December 2004, the legislation was amended to allow
      the use of the NDNAD to assist in the identification of a deceased person or of a
      body part where death has occurred from natural causes or from a natural
      disaster. The UK NDNAD now contains the DNA profiles of approximately 6 million
      individuals representing 9.6% of the UK population. As the science of DNA
      profiling advanced, the National DNA Database provided a potential resource for
      increased intelligence beyond the direct matching for which it was originally
      created. The familial searching service offered to the police by several UK
      forensic science providers exploits the size and geographic coverage of the NDNAD
      and the fact that close relatives of an offender may share a significant
      proportion of that offender's DNA profile and will often reside in close
      geographic proximity to him or her. Between 2002 and 2011 Forensic Science
      Service Ltd. (FSS) provided familial search services to support 188 police
      investigations, 70 of which are still active cases. This technique, which may be
      used in serious crime cases or in 'cold case' reviews when there are few or no
      investigative leads, has led to the identification of 41 perpetrators or
      suspects. In this paper we discuss the processes, utility, and governance of the
      familial search service in which the NDNAD is searched for close genetic
      relatives of an offender who has left DNA evidence at a crime scene, but whose
      DNA profile is not represented within the NDNAD. We discuss the scientific basis
      of the familial search approach, other DNA-based methods for eliminating
      individuals from the candidate lists generated by these NDNAD searches, the value
      of filtering these lists by age, ethnic appearance and geography and the
      governance required by the NDNAD Strategy Board when a police force commissions a
      familial search. We present the FSS data in relation to the utility of the
      familial searching service and demonstrate the power of the technique by
      reference to casework examples. We comment on the uptake of familial searching of
      DNA databases in the USA, the Netherlands, Australia, and New Zealand. Finally,
      following the adverse ruling by the European Court of Human Rights against the UK
      in regard to the S & Marper cases and the consequent introduction of the
      Protection of Freedoms Act (2012), we discuss the impact that changes to
      regulations concerning the storage of DNA samples will have on the continuing
      provision of familial searching of the National DNA Database in England and
      Wales.

PMID- 24315583
TI  - I-DNASE21 system: development and SWGDAM validation of a new STR 21-plex
      reaction.
AB  - I-DNASE21 is a new STR multiplex system that amplifies 21 STR autosomal loci,
      plus the amelogenin locus in one reaction. This system has been designed to
      analyze all the STR loci included in the Combined DNA Index System (CODIS),
      Interpol Standard Set of Loci (ISSL), Extended European Standard Set (ESS
      Extended), UK National Criminal Intelligence DNA Database (NDNAD) and German Core
      loci (GCL). This manuscript presents the validation of the I-DNASE21 system
      according to the revised guidelines issued by the Scientific Working Group on DNA
      Analysis Methods (SWGDAM). The results of this validation, added to the extremely
      high discriminatory power showed, suggest that I-DNASE21 could be a potentially
      helpful tool for identification and kinship determination even in complex
      paternity cases. 

PMID- 24315584
TI  - Characterising the STR locus D6S1043 and examination of its effect on stutter
      rates.
AB  - The forensic analysis of DNA is most often undertaken by the amplification of
      short tandem repeats (STR) using the polymerase chain reaction (PCR). DNA
      amplification can result in production of the target allele amplicon and a by
      product called stutter. Stutter is the result of the miscopy of the target allele
      and is typically one repeat smaller. Stutter is traditionally described as a
      ratio of stutter and allele height; stutter ratio (SR). The challenge to DNA
      profile interpretation is most serious whenever stutter products are of a similar
      height to the minor allelic peaks in a mixed DNA profile. An accurate assignment
      of peaks and the prediction of their height is important when objectively
      interpreting forensic DNA profiles. The longest uninterrupted stretch (LUS) of
      tandem repeats within the allele has previously been shown to be a good predictor
      of stutter ratio. LUS is determined by sequencing a range of observed alleles at
      a locus. The locus D6S1043 is a relatively new locus to appear in commercial
      forensic DNA testing kits. To date however, there has been no comprehensive
      report of sequencing of this locus. In this work, we sequence a sample of D6S1043
      alleles to determine LUS values and investigate allele repeat number and LUS as
      explanatory variables for SR. 

PMID- 24315585
TI  - Assessment of DNA damage induced by terrestrial UV irradiation of dried
      bloodstains: forensic implications.
AB  - Few publications have detailed the nature of DNA damage in contemporary (i.e. non
      ancient) dried biological stains. The chief concern, from a forensic standpoint,
      is that the damage can inhibit polymerase-mediated primer extension, ultimately
      resulting in DNA typing failure. In the work described here, we analyzed the
      effects of UVA and UVB irradiation on cell-free solubilized DNA, cell-free
      dehydrated DNA and dehydrated cellular DNA (from bloodstains). After UV exposure
      ranging from 25 J cm(-2) to 1236 J cm(-2), we assayed for the presence of
      bipyrimidine photoproducts (BPPPs), oxidative lesions and strand breaks,
      correlating the damage with the inhibition of STR profiling. Subsequent to
      irradiation with either UVA and UVB, the incidence of BPPPs, oxidative products
      and strand breaks were observed in decreasing quantities as follows: cell-free
      solubilized DNA>cell-free dehydrated DNA>bloodstain DNA. UVA irradiation did not
      result in even the partial loss of a STR profile in any sample tested. Somewhat
      different results were observed after genetic analysis of UVB exposed samples, in
      that the ability to produce a complete STR profile was affected earliest in
      bloodstain DNA, next in cell-free solubilized DNA and not at all in cell-free
      dehydrated DNA. Therefore, it is likely that other types of damage contributed to
      allele-drop-out in these samples but remained undetected by our assays, whereby
      the endonucleases did not react with the lesions or the presence of the lesions
      was masked by strand breaks. Under the conditions of the study, strand breaks
      appeared to be the predominant types of damage that ultimately resulted in DNA
      typing failure from physiological stains, although some evidence suggested
      oxidative damage may have played a role as well.

PMID- 24315586
TI  - DNA paternity tests in Spain without the mother's consent: the legal
      responsibility of the laboratories.
AB  - It is technically feasible to perform paternity diagnosis testing solely
      involving an alleged father and his descendent. However, there are serious legal
      and ethical problems for forensic genetics laboratories when it comes to
      paternity testing cases for investigating the alleged father-child relationship
      if the biological mother has not given consent to access her genetic information.
      Based on the Spanish Constitution, the new Code of Ethics of the Spanish Medical
      Association includes several articles on studies about genetic information and
      their acceptance by all the individuals involved. This problem is greater when
      the child is a minor, mentally incapacitated or psychologically incapable,
      because current Spanish law requires informed consent from legal representatives,
      but the law does not typify what happens when one parent gives consent (the
      putative father) and the other parent (the mother) does not agree. The aim of
      this study is to put forward legal solutions to avoid potential legal problems. 

PMID- 24315587
TI  - Global population variability in Qiagen Investigator HDplex STRs.
AB  - Supplementary short tandem repeats (STRs) can be added to forensic analyses if
      the 15-24 core STRs in routine use fail to give sufficient discrimination power
      in complex identification or relationship testing scenarios. In this study, 10 of
      12 supplementary STRs in the Qiagen Investigator HDplex kit (SE33, D2S1360,
      D3S1744, D4S2366, D5S2500, D6S474, D7S1517, D8S1132, D10S2325, D21S2055) were
      genotyped in 941 individuals from the 51 populations of the CEPH Human Genome
      Diversity Panel (HGDP-CEPH). The other two components of the 12-STR HDplex kit
      are established STRs D12S391 and D18S51 that we previously genotyped for the HGDP
      CEPH panel. We describe the rare alleles identified and outline allele frequency
      distributions in the seven population groups of the HGDP-CEPH panel. The HDplex
      STRs novel to forensic application were found to be both highly informative and
      comparable in their power across all populations studied: at least six of the
      nine loci showing above average forensic discrimination power in each population
      group. In some rare instances certain low frequency alleles in D2S1360 were found
      to overlap in mobility with the neighbouring allele size ranges of D12S391, as
      well as those of D7S1517 with neighbouring D3S1744 and D10S2325 with neighbouring
      SE33. Lastly, since expanded five-dye multiplex kits of 20 STRs (Promega
      Powerplex 21) and 22 STRs (Promega Powerplex Fusion) have recently been
      introduced, we assess through simulations the increased power to analyse pairwise
      relationships in deficient pedigrees that can be expected from an optimum kit
      pair: combining HDplex with either of the above sets to provide 30 or 32 unique
      STRs and just two overlapping loci.

PMID- 24315588
TI  - Development of a 24-locus multiplex system to incorporate the core loci in the
      Combined DNA Index System (CODIS) and the European Standard Set (ESS).
AB  - The 24-locus multiplex system allows co-amplification and fluorescent detection
      of 24 loci (23 STR loci and Amelogenin), including STR loci in the Combined DNA
      Index System (CODIS) and the ESS (European Standard Set) as well as five
      additional loci (D2S1338, D6S1043, D19S433, Penta D and Penta E) commonly used in
      commercial kits. It facilitates data sharing and minimizes adventitious matches
      within national or between international DNA databases. Additionally, the system
      can amplify directly from blood and buccal samples spotted on filter paper and
      swabs and reduce the cycling time to less than one hour and a half. Primers,
      internal size standard, allelic ladders and matrix standard set were designed and
      created in-house with a design strategy to work in this multiplex. Developmental
      validation experiments followed the Scientific Working Group on DNA Analysis
      Methods (SWGDAM) and the Chinese National Standard (GA/T815-2009) guidelines. The
      system was evaluated by species specificity, sensitivity, stability, precision
      and accuracy, case-type samples, population, mixture and PCR-based studies. The
      results demonstrate that the 24-locus multiplex system is a robust and reliable
      identification assay as required for forensic DNA typing and databasing. 

PMID- 24315589
TI  - Examination of DNA yield rates for different skeletal elements at increasing post
      mortem intervals.
AB  - Identification of contemporary human remains by DNA STR testing is mainly limited
      by the ability to isolate sufficient amounts of DNA from the skeletal samples. A
      key part of this work relies on selection of the skeletal element with the best
      chance of obtaining a DNA STR profile. DNA was extracted from 55 bone samples,
      from 3 recently skeletonized individuals, representing most element types in the
      human body. Comparison of DNA yields from samples within an individual showed
      that the small cancellous bones on average have much higher amounts of DNA per
      unit mass than dense cortical bones. Complete 16 locus STR profiles were obtained
      for all 3 individuals from 36 of the element types, 10 had full profiles for 2 of
      the 3 individuals, 3 had full profiles for 1 of the 3 and 5 did not have any full
      profiles. The sample types with the least STR loci were from the arms. Ten
      skeletal elements were tested from 12 additional skeletons ranging from 3-21
      years post mortem interval (PMI). At increasing PMI the small cancellous bones
      continued to yield more DNA and STR loci than the cortical bones. These findings
      suggest that the current recommendation for selection of long cortical bone
      samples for DNA testing of skeletal remains should be re-evaluated. 

PMID- 24315590
TI  - Population genetic data for 15 X chromosomal short tandem repeat markers in three
      U.S. populations.
AB  - 314 African American, 434 U.S. Caucasian, and 398 U.S. Hispanic individuals were
      typed at X STR markers DXS6795, DXS9902, DXS8378, DXS7132, DXS6803, DXS6789,
      DXS7424, DXS101, GATA172D05, DXS7130, GATA165B12, HPRTB, GATA31E08, DXS10147,
      DXS7423. High forensic efficiency parameter values confirm the potential
      usefulness of these markers in certain specific kinship situations involving
      female offspring as well as identity testing. Alleles previously unobserved in
      U.S. populations were noted in this study at 8 different markers. Additionally,
      null alleles and a triallelic pattern were observed and described. Pairwise
      comparisons indicated consistency with similar published populations at
      overlapping markers. These data represent a substantial increase in the quantity
      of U.S. X chromosomal short tandem repeat data available to the community. 

PMID- 24315591
TI  - Characterization of mutations and sequence variants in the D21S11 locus by next
      generation sequencing.
AB  - We sequenced the D21S11 locus in 77 individuals from Danish paternity cases using
      454 FLX next generation sequencing (NGS) technology. All samples were also typed
      with the AmpFlSTR Profiler Plus or the AmpFlSTR Identifiler PCR Amplification
      kits as part of paternity investigations. In 18 of the confirmed trios, a genetic
      inconsistency was observed between one of the parents and the child at the D21S11
      locus. NGS of the D21S11 locus revealed which allele had mutated from which
      parent to the child in 13 of these trios. All characterized mutations could be
      explained by single-step mutations in the longest sub-repeat of D21S11. A total
      of 53 of the 77 sequenced samples originated from unrelated individuals. Twenty
      different D21S11 alleles were detected by NGS in these individuals whereas only
      13 different alleles were observed with fragment analysis. Several alleles had
      the same lengths but different sequences, e.g. four and three different alleles
      were detected by NGS with lengths determined by CE corresponding to allele 30 and
      allele 31, respectively.

PMID- 24315592
TI  - Detection of the deletion on Yp11.2 in a Chinese population.
AB  - Sex determination tests based on Amelogenin gene as part of commercial PCR
      multiplex reaction kits have been widely applied in forensic DNA analysis.
      Mutations that cause dropout of Y chromosomal Amelogenin gene (AMELY) could lead
      to errors in gender determination and mixture interpretation. To infer the
      mechanism and estimate the dropout frequency of AMELY and adjacent Y-STRs, we
      studied 3 samples with AMELY dropout combined with DYS458 and/or DYS456 and 37
      samples with DYS456 dropout. DYS456, DYS458 and AMELY are located in the Yp11.2
      region. The singleplex amplification system showed the null alleles could be
      caused by fragment deletion in Yp11.2 rather than a point mutation in the primer
      binding region. After detection of the 17 Y-STR and 77 STS markers, the deletion
      map showed different patterns. The DYS456-AMELY-DYS458 deletion pattern was the
      largest, breaking from 3.60 Mb to 8.29 Mb in the Y chromosome, and the overall
      frequency was 0.0077%. The AMELY-DYS458 deletion pattern was broke from 6.74 Mb
      to 9.17 Mb, with a 0.0155% frequency. The DYS456 negative pattern was
      concentrated in two main deletion regions, with a 0.8220% frequency. The
      frequency of all negative pattern was 0.0155%. All the AMELY-DYS458 and DYS456
      AMELY-DYS458, and 92% of the DYS456 deletion patterns belonged to Hg O3, the rest
      belonged to Hg Q. The DYS456 deletion pattern was first reported in Chinese
      population. The current and previous findings suggest additional gender test for
      ambiguous sex determination may be required.

PMID- 24315593
TI  - Population genetics of insertion-deletion polymorphisms in South Koreans using
      Investigator DIPplex kit.
AB  - We assessed the applicability of 30 insertion-deletion polymorphisms (INDELs) in
      forensic use and the level of genetic diversity in South Korea (n=373) using the
      Investigator DIPplex kit (Qiagen). Allele frequencies, heterozygocities, and
      forensic efficacy parameters were determined. No deviation from Hardy-Weinberg
      equilibrium was observed for any of the INDEL markers. A high level of
      discrimination power was observed (combined power of discrimination:
      0.99999999995). The combined match probability value was 2.84 * 10(-11) and the
      mean typical paternity indices were 0.878. Furthermore, we found one microvariant
      allele at HLD93 (rs2307570) that has not been reported. We expect that these 30
      loci of INDEL markers will be useful for forensic identification and paternity
      testing in the South Korean population.

PMID- 24315594
TI  - Enhanced recovery of spermatozoa and comprehensive lysis of epithelial cells from
      sexual assault samples having a low cell counts or aged up to one year.
AB  - Differential extraction (DE) is the most common method for processing sexual
      assault samples, allowing for the simultaneous recovery of sperm and epithelial
      cells from the swab with the separation of sperm cells from epithelial cell DNA
      by exploiting the differences in the cell membrane susceptibility to detergents.
      However, sperm cell recovery when using DE is generally 40-50% [1], which can
      reduce the probability of obtaining a STR profile of the semen contributor,
      especially if the sample is aged or has a low number of sperm cells. Here, we
      present a novel buffer, containing SDS and ProK that, when used as an initial
      incubation buffer, enhances sperm cell recovery to as high as 90%, representing a
      200-300% increase over conventional DE buffer. Adjusting the incubation time and
      temperature provided high, reproducible sperm cell yields. Sample vortexing and
      replacement of SDS with sodium octyl sulfate (SOS), another sulfate-based anionic
      detergent, did not provide any further enhancement of the sperm cell recoveries.
      Furthermore, the one-step buffer provided up to a 300% increase in recovery over
      the conventional DE buffer when used on samples aged up to one year. STR analysis
      of samples containing 500 or more sperm cells treated with this buffer showed
      comparable results (i.e., full STR profiles; 16 of 16 loci) to those obtained
      using a conventional DE buffer. Finally, when the sample contained only 400 sperm
      cells (recovered in 100MUL volume, then extracted), substantially more STR loci
      (14 of 16) were generated using the novel buffer in comparison to the
      conventional DE buffer (4 of 16 loci). This work demonstrates that this buffer
      may be useful as an alternative for the initial sample incubation step in
      differential extraction, particularly for aged or samples known to have a low
      number of sperm cells. 

PMID- 24315595
TI  - Validation of two canine STR multiplex-assays following the ISFG recommendations
      for non-human DNA analysis.
AB  - To gain general acceptance forensic DNA testing in animals needs to improve
      standardization of analysis methods and data interpretation. Recently, the
      International Society of Forensic Genetics (ISFG) took particular care of this
      topic by publishing recommendations for forensic non-human DNA analysis following
      the successful example of human DNA analysis in order to provide a basis for
      harmonization of the still existing inter-laboratory variability. By following
      these recommendations we demonstrate the performance of two short tandem repeat
      (STR) multiplexes for forensic identity testing of canine biological material.
      Thirteen STRs and two sex-specific markers were selected and validated according
      to the ISFG guidelines. Population genetic parameters were calculated based on
      295 dog samples collected in Austria (124) and Germany (171). A repeat-based
      nomenclature of the mainly tetrameric STRs and corresponding allelic ladders are
      presented. All 146 different alleles included in the ladders were sequenced for
      correct allele calling. Additionally, a canine cell line (DH82-D3167) was
      evaluated as standard reference material. 

PMID- 24315596
TI  - A 50-SNP assay for biogeographic ancestry and phenotype prediction in the U.S.
      population.
AB  - When an STR DNA profile obtained from crime scene evidence does not match
      identified suspects or profiles from available databases, further DNA analyses
      targeted at inferring the possible ancestral origin and phenotypic
      characteristics of the perpetrator could yield valuable information. Single
      Nucleotide Polymorphisms (SNPs), the most common form of genetic polymorphisms,
      have alleles associated with specific populations and/or correlated to physical
      characteristics. We have used single base primer extension (SBE) technology to
      develop a 50 SNP assay (composed of three multiplexes) designed to predict
      ancestry among the primary U.S. populations (African American, East Asian,
      European American, and Hispanic American/Native American), as well as
      pigmentation phenotype (eye, hair, and skin color) among European American. We
      have optimized this assay to a sensitivity level comparable to current forensic
      DNA analyses, and shown robust performance on forensic-type samples. In addition,
      we developed a prediction model for ancestry in the U.S. population, based on the
      random match probability and likelihood ratio formulas already used in forensic
      laboratories. Lastly, we evaluated the biogeographic ancestry prediction model
      using a test set, and we evaluated an existing model for eye color with our U.S.
      sample set. Using these models with recommended thresholds, the 50 SNP assay
      provided accurate ancestry information in 98.6% of the test set samples, and
      provided accurate eye color information in 61% of the European samples tested
      (25% were inconclusive and 14% were incorrect). This method, which uses equipment
      already available in forensic DNA laboratories, is recommended for use in U.S.
      forensic casework to provide additional information about the donor of a DNA
      sample when the STR profile has not been linked to an individual. 

PMID- 24315597
TI  - Identification of person and quantification of human DNA recovered from
      mosquitoes (Culicidae).
AB  - Mosquitoes (Culicidae) are widespread insects and can be important in forensic
      context as a source of human DNA. In order to establish the quantity of human DNA
      in mosquitoes' gut after different post-feeding interval and for how long after
      taking a bloodmeal the human donor could be identified, 174 blood-engorged
      mosquitoes (subfamily Anophelinae and Culicinae) were captured, kept alive and
      sacrificed at 8h intervals. Human DNA was amplified using forensic PCR kits
      (Identifiler, MiniFiler, and Quantifiler). A full DNA profiles were obtained from
      all Culicinae mosquitoes (74/74) up to 48 h and profiling was successful up to 88
      h after a bloodmeal. Duration of post-feeding interval had a significant negative
      effect on the possibility of obtaining a full profile (p<0.001), and logistic
      regression found that the probability of obtaining the full profile is 15.5% less
      for every 8h increase in post-feeding interval. Culicinae mosquitoes are a
      suitable source of human DNA for forensic STR kits more than three days after a
      bloodmeal. Human DNA recovered from mosquito can be used for matching purposes
      and could be useful in revealing spatial and temporal relation of events that
      took place at the crime scene. Therefore, mosquitoes at the crime scene, dead or
      alive, could be a valuable piece of forensic evidence.

PMID- 24315598
TI  - 'Stochastic' effects at balanced mixtures: a calibration study.
AB  - DNA mixtures are challenging not only at low template DNA level but also at
      highly balanced quantitative ratio. In this latter case, interpretation may be
      complicated by the joint action of combinatorial uncertainty and stochastic
      effects of the PCR. We explore this particular and so far little noticed aspect
      of mixture interpretation by first providing a complete quantitative
      combinatorial analysis of the two-person mixture model (2PM) at highly balanced
      ratio of contributors, and then by carrying out a calibration study of the 2PM
      model on good quality experimental mixtures. The calibration tests provided the
      evidence for the existence of irregular distribution of peak heights, that can
      misguide the correct genotype assignment at high template ratios too. Repeating
      the experiment, performing Bayesian analysis to the whole evidence and developing
      a careful joint prediction of all plausible genotype datasets is highly mandatory
      in these cases, prior to set evidentiary LRs and use them in court. 

PMID- 24315599
TI  - Northern Slavs from Serbia do not show a founder effect at autosomal and Y
      chromosomal STRs and retain their paternal genetic heritage.
AB  - Studies on Y-chromosomal markers revealed significant genetic differentiation
      between Southern and Northern (Western and Eastern) Slavic populations. The
      northern Serbian region of Vojvodina is inhabited by Southern Slavic Serbian
      majority and, inter alia, Western Slavic (Slovak) and Eastern Slavic (Ruthenian)
      minorities. In the study, 15 autosomal STR markers were analysed in unrelated
      Slovaks, Ruthenians and Serbs from northern Serbia and western Slovakia.
      Additionally, Slovak males from Serbia were genotyped for 17 Y-chromosomal STR
      loci. The results were compared to data available for other Slavic populations.
      Genetic distances for autosomal markers revealed homogeneity between Serbs from
      northern Serbia and Slovaks from western Slovakia and distinctiveness of Serbian
      Slovaks and Ruthenians. Y-STR variation showed a clear genetic departure of the
      Slovaks and Ruthenians inhabiting Vojvodina from their Serbian neighbours and
      genetic similarity to the Northern Slavic populations of Slovakia and Ukraine.
      Admixture estimates revealed negligible Serbian paternal ancestry in both
      Northern Slavic minorities of Vojvodina, providing evidence for their genetic
      isolation from the Serbian majority population. No reduction of genetic diversity
      at autosomal and Y-chromosomal markers was found, excluding genetic drift as a
      reason for differences observed at autosomal STRs. Analysis of molecular variance
      detected significant population stratification of autosomal and Y-chromosomal
      microsatellites in the three Slavic populations of northern Serbia, indicating
      necessity for separate databases used for estimations of frequencies of autosomal
      and Y-chromosomal STR profiles in forensic casework. Our results demonstrate that
      regarding Y-STR haplotypes, Serbian Slovaks and Ruthenians fit in the Eastern
      European metapopulation defined in the Y chromosome haplotype reference database.

PMID- 24315600
TI  - "Would you accept having your DNA profile inserted in the National Forensic DNA
      database? Why?" Results of a questionnaire applied in Portugal.
AB  - The creation and expansion of forensic DNA databases might involve potential
      threats to the protection of a range of human rights. At the same time, such
      databases have social benefits. Based on data collected through an online
      questionnaire applied to 628 individuals in Portugal, this paper aims to analyze
      the citizens' willingness to donate voluntarily a sample for profiling and
      inclusion in the National Forensic DNA Database and the views underpinning such a
      decision. Nearly one-quarter of the respondents would indicate 'no', and this
      negative response increased significantly with age and education. The overriding
      willingness to accept the inclusion of the individual genetic profile indicates
      an acknowledgement of the investigative potential of forensic DNA technologies
      and a relegation of civil liberties and human rights to the background, owing to
      the perceived benefits of protecting both society and the individual from crime.
      This rationale is mostly expressed by the idea that all citizens should
      contribute to the expansion of the National Forensic DNA Database for reasons
      that range from the more abstract assumption that donating a sample for profiling
      would be helpful in fighting crime to the more concrete suggestion that everyone
      (criminals and non-criminals) should be in the database. The concerns with the
      risks of accepting the donation of a sample for genetic profiling and inclusion
      in the National Forensic DNA Database are mostly related to lack of control and
      insufficient or unclear regulations concerning safeguarding individuals' data and
      supervising the access and uses of genetic data. By providing an empirically
      grounded understanding of the attitudes regarding willingness to donate voluntary
      a sample for profiling and inclusion in a National Forensic DNA Database, this
      study also considers the citizens' perceived benefits and risks of operating
      forensic DNA databases. These collective views might be useful for the formation
      of international common ethical standards for the development and governance of
      DNA databases in a framework in which the citizens' perspectives are taken into
      consideration. 

PMID- 24315601
TI  - Comparative performance between "next generation" multiplex systems and the new
      European Standard Set of STR markers in the Portuguese Population.
AB  - Various multiplex STR systems have been developed by the major commercial
      companies in the forensic genetics field to comply with the recent establishment
      of the global European Standard Set (ESS) of markers. Of the various alternatives
      available, our laboratory decided to test the recent ESSplex Plus system (Qiagen)
      and the NGM kit (Life Technologies), which share the same 15 STR loci and
      comprise the most recently established ESS markers (D1S1656, D2S441, D10S1248,
      D12S391 and D22S1045). Apart from evaluating the kits' technical performances, a
      population and segregation study was carried out on a Portuguese sample, with the
      aim of introducing the ESS markers in routine forensic casework. A total of 370
      individuals were sampled for this purpose, comprising 120 true trios (125
      fathers, 125 mothers and 120 sons/daughters). No deviations from Hardy-Weinberg
      equilibrium were detected for the five new loci in the Portuguese population and
      no genotyping inconsistencies were observed between kits. Parameters of forensic
      interest revealed that, of the five ESS markers, D1S1656 was the most informative
      in our sample. Comparison of performances between all autosomal multiplex systems
      available in our laboratory (ESSplex Plus, NGM, Identifiler Plus and Powerplex 16
      HS), revealed that the multiplex kits with the ESS markers generally showed
      better performances and, among these, the ESSplex Plus kit showed slightly higher
      sensitivity and a better detection of degraded DNA information. 

PMID- 24315602
TI  - Identification of new primer binding site mutations at TH01 and D13S317 loci and
      determination of their corresponding STR alleles by allele-specific PCR.
AB  - Several commercial multiplex PCR kits for the amplification of short tandem
      repeat (STR) loci have been extensively applied in forensic genetics.
      Consequently, large numbers of samples have been genotyped, and the number of
      discordant genotypes observed has also increased. We observed allele dropout with
      two novel alleles at the STR loci TH01 and D13S317 during paternity testing using
      the AmpFlSTR Identifiler PCR Amplification Kit. The lost alleles reappeared when
      alternative PCR primer pairs were used. A sequence analysis revealed a G-to-A
      substitution 82 bases downstream of the last TCAT motif of the repeat region at
      the TH01 locus (GenBank accession: D00269) and a G-to-T substitution 90 bases
      upstream of the first TATC motif of the repeat region at the D13S317 locus
      (GenBank accession: G09017). The frequencies of these two point mutations were
      subsequently investigated in the Chinese population using sequence-specific
      primer PCR (SSP-PCR), but neither of these mutations was detected in any of the
      samples tested. In addition, the DNA samples in which the mutations were
      identified were amplified to type the point mutations by SSP-PCR to determine the
      corresponding STR alleles at the two loci. Subsequently, the amplified PCR
      products with different point mutations and STR repeat numbers were directly
      sequenced because this strategy overcomes the appearance overlapping peaks
      generated by different STR alleles and accurately characterizes genotypes. Thus,
      our findings not only provide useful information for DNA databases and forensic
      identification but also establish an effective strategy for typing STR alleles
      with primer binding site mutations.

PMID- 24315603
TI  - An integratable microfluidic cartridge for forensic swab samples lysis.
AB  - Fully automated rapid forensic DNA analysis requires integrating several
      multistep processes onto a single microfluidic platform, including substrate
      lysis, extraction of DNA from the released lysate solution, multiplexed PCR
      amplification of STR loci, separation of PCR products by capillary
      electrophoresis, and analysis for allelic peak calling. Over the past several
      years, most of the rapid DNA analysis systems developed started with the
      reference swab sample lysate and involved an off-chip lysis of collected
      substrates. As a result of advancement in technology and chemistry, addition of a
      microfluidic module for swab sample lysis has been achieved in a few of the rapid
      DNA analysis systems. However, recent reports on integrated rapid DNA analysis
      systems with swab-in and answer-out capability lack any quantitative and
      qualitative characterization of the swab-in sample lysis module, which is
      important for downstream forensic sample processing. Maximal collection and
      subsequent recovery of the biological material from the crime scene is one of the
      first and critical steps in forensic DNA technology. Herein we present the
      design, fabrication and characterization of an integratable swab lysis cartridge
      module and the test results obtained from different types of commonly used
      forensic swab samples, including buccal, saliva, and blood swab samples,
      demonstrating the compatibility with different downstream DNA extraction
      chemistries. This swab lysis cartridge module is easy to operate, compatible with
      both forensic and microfluidic requirements, and ready to be integrated with our
      existing automated rapid forensic DNA analysis system. Following the
      characterization of the swab lysis module, an integrated run from buccal swab
      sample-in to the microchip CE electropherogram-out was demonstrated on the
      integrated prototype instrument. Therefore, in this study, we demonstrate that
      this swab lysis cartridge module is: (1) functionally, comparable with routine
      benchtop lysis, (2) compatible with various types of swab samples and
      chemistries, and (3) integratable to achieve a micro total analysis system
      (MUTAS) for rapid DNA analysis. 

PMID- 24315604
TI  - Object-oriented Bayesian networks for evaluating DIP-STR profiling results from
      unbalanced DNA mixtures.
AB  - The genetic characterization of unbalanced mixed stains remains an important area
      where improvement is imperative. In fact, with current methods for DNA analysis
      (Polymerase Chain Reaction with the SGM Plus multiplex kit), it is generally not
      possible to obtain a conventional autosomal DNA profile of the minor contributor
      if the ratio between the two contributors in a mixture is smaller than 1:10. This
      is a consequence of the fact that the major contributor's profile 'masks' that of
      the minor contributor. Besides known remedies to this problem, such as Y-STR
      analysis, a new compound genetic marker that consists of a Deletion/Insertion
      Polymorphism (DIP), linked to a Short Tandem Repeat (STR) polymorphism, has
      recently been developed and proposed elsewhere in literature. The present paper
      reports on the derivation of an approach for the probabilistic evaluation of DIP
      STR profiling results obtained from unbalanced DNA mixtures. The procedure is
      based on object-oriented Bayesian networks (OOBNs) and uses the likelihood ratio
      as an expression of the probative value. OOBNs are retained in this paper because
      they allow one to provide a clear description of the genotypic configuration
      observed for the mixed stain as well as for the various potential contributors
      (e.g., victim and suspect). These models also allow one to depict the assumed
      relevance relationships and perform the necessary probabilistic computations.

PMID- 24315605
TI  - Evaluation of DNAstable for DNA storage at ambient temperature.
AB  - Preserving DNA is important for validation of prospective and retrospective
      analyses, requiring many expensive types of equipment (e.g., freezers and back-up
      generators) and energy. While freezing is the most common method for storing
      extracted DNA evidence or well-characterized DNA samples for validation studies,
      DNAstable (Biomatrica), a commercially available medium for room temperature
      storage of DNA extracts was evaluated in this study. Two groups of samples
      consisting of different DNA quantities were investigated, one ranging from 20 to
      400 ng (group 1) and the other one ranging from 1.4 to 20 ng (group 2). The DNA
      samples with and without DNAstable were stored at four different temperatures
      [~25  degrees C (room temperature), -20  degrees C, 37  degrees C or 50  degrees
      C]. DNA degradation over several months was monitored by SYBR Green-based qPCR
      assays and by PCR amplification of the core CODIS STR markers for group 1 and 2
      DNA samples, respectively. For the time points tested in this study (up to 365
      days), the findings indicate that the -20  degrees C controls and the DNAstable
      protected samples at room temperature provided similar DNA recoveries that were
      higher compared to the unprotected controls kept at RT, 37  degrees C or 50 
      degrees C. These results suggest that DNAstable can protect DNA samples with
      effectiveness similar to that of the traditional -20  degrees C freezing method.
      In addition, extrapolations from accelerated aging experiments conducted at high
      temperatures support that DNAstable is an effective technology for preserving
      purified DNA at room temperature with a larger protective impact on DNA samples
      of low quantity (<20 ng).

PMID- 24315606
TI  - Evaluation of tapelifting as a collection method for touch DNA.
AB  - The use of tapelifting for collection of touch DNA from fabrics is routine in
      many jurisdictions. However, there is a paucity of data relating to the
      effectiveness of different types of tapes for tapelifting, the amount of
      tapelifting required to generate a useful profile, and whether or not tapelifting
      is more effective than swabbing from various substrates. This research
      investigates these questions by comparing two tapes of different adhesive
      strength currently used in forensic casework (Scotch Magic tape and Scenesafe
      FAST minitapes), for sampling from touch deposits on four different fabrics
      cotton flannelette, cotton drill woven fabric, polyester/cotton plain woven
      fabric and polyester strapping. Touch DNA was deposited on four replicates of
      each substrate. Separate areas of each substrate replicate were sampled, either
      by taping with one of the two tapes or by wet/dry swabbing with cotton swabs.
      Tape was applied over the defined sampling area once or repeatedly for various
      numbers of applications. DNA was extracted, quantified and profiled from all tape
      and swab samples as well as the corresponding sampled substrates. Significantly
      more DNA was extracted, and a higher proportion of alleles detected, from
      Scenesafe FAST tape than from Scotch Magic tape. The amount of DNA and number of
      donor alleles detected generally increased as the tape was reapplied to the
      surface, although a threshold of collection was seen for both types of tape. For
      two out of four substrates, taping with Scenesafe FAST collected more DNA than
      swabbing and, for three substrates, generated a greater median number of donor
      alleles. There was no significant difference in numbers of alleles between
      swabbing and taping from flannelette. Based on these findings, it is recommended
      that a tape with stronger adhesion (such as Scenesafe FAST tapelifters) is
      generally preferable; that more than one application of tape is suggested
      (however, increasing the amount of times the area is sampled can diminish
      collection efficiency); and that there is an advantage using tapelifting rather
      than swabbing for fabrics unless, such as with flannelette, there are many loose
      fibres easily removed during the sampling process.

PMID- 24315607
TI  - Developing a novel panel of genome-wide ancestry informative markers for bio
      geographical ancestry estimates.
AB  - Inferring the ancestral origin of DNA samples can be helpful in correcting
      population stratification in disease association studies or guiding crime
      investigations. Populations throughout the world vary in appearance features and
      biological characteristics. Based on this idea, we performed a genome-wide scan
      for SNPs within genes that are related to physical and biological traits. Using
      the HapMap database, we screened 52 genes and their flanking regions. Thirty-five
      SNPs that displayed highly contrasting allele frequencies (F(st)>0.3, linkage
      disequilibrium r(2)<0.2, and Hardy-Weinberg equilibrium P>0.001) among Africans,
      Europeans, and East Asians were selected and validated. A multiplexed assay was
      developed to genotype these 35 SNPs in 357 individuals from 10 populations
      worldwide. This panel provided accurate estimates of individual ancestry
      proportions with balanced discriminatory power among the three continental
      ancestries: Africans, Europeans, and East Asians. It also proved very effective
      in evaluating admixed populations living in joint regions of continents (e.g.,
      Uyghurs and Indians) and discriminating some subpopulations within each of the
      three continents. Structure analysis was performed to establish and evaluate the
      panel of ancestry-informative markers, and the components of each population were
      also described to indicate the structural composition. The 21 population
      structures in our study are consistent with geographic patterns, and individuals
      were properly assigned to their original ancestral populations with proportion
      analyses and random match probability calculations. Thus, the panel and its
      population information will be useful resources to minimize the effects of
      population stratification in association analyses and to assign the most likely
      origin of an unknown DNA contributor in forensic investigations.

PMID- 24315608
TI  - Non-uniform phenotyping of D12S391 resolved by second generation sequencing.
AB  - Non-uniform phenotyping of five case work samples were observed in the D12S391
      locus. The samples were typed at least twice with the AmpFlSTR NGM SElect PCR
      Amplification Kit and different alleles were called with GeneMapper ID-X in the
      different experiments. Detailed analyses of the electropherograms suggested that
      the individuals were heterozygous with two alleles that differed in size by one
      nucleotide. This was confirmed by amplifying the samples with the PowerPlex ESX
      17 system. D12S391 is a complex STR with variable numbers of AGAT and AGAC
      repeats. Second generation sequencing revealed that separation of two alleles
      differing by one nucleotide in length was poor if the number of AGAT repeats in
      the short allele was higher than in the long allele. A total of 45 individuals
      with microvariants or off-ladder alleles in D12S391 were sequenced. Thirty
      different alleles were detected and sixteen of these were not previously
      reported.

PMID- 24315609
TI  - Wildlife DNA forensics against crime: resolution of a case of tortoise theft.
AB  - A paternity test was used to investigate a robbery case involving captive
      individuals of Greek tortoise (Testudo graeca). Six tortoises were allegedly
      stolen from a private breeder and offered for sale on the web by the supposed
      thief. The stolen tortoises were confiscated by the rangers of the State Forestry
      Corps (CFS). A panel of 14 autosomal microsatellite loci was used to genotype the
      seized tortoises and ten individuals assumed to be legally owned by the breeder.
      Kinship analyses reliably reconstructed the tortoise pedigree, demonstrating
      parent-offspring relationships among the owned and the stolen tortoises. As
      correctly declared by the breeder, four of the six stolen individuals belonged to
      the same family group of the ten legally owned tortoises. Results indicate that
      genetic identification procedures can provide valuable evidence and give useful
      support against illegal wildlife traffic. 

PMID- 24315611
TI  - Reduction of stutter ratios in short tandem repeat loci typing of low copy number
      DNA samples.
AB  - Increased height of stutter peaks is a phenomenon with low copy number (LCN)
      short tandem repeat (STR) typing that can impact interpretation. An alternative
      strategy of lowering the annealing/extension temperature (LT) at 56  degrees C
      was designed to attempt to decrease the heights of stutter peaks. STR typing
      results were generated in terms of stutter ratios using LT-PCR conditions and
      compared with data obtained using standard (STD) PCR conditions. DNA samples
      ranging from 100 to 25 pg were amplified using reagents contained in the AmpFlSTR
      Identifiler PCR Amplification or AmpFlSTR Identifiler Plus PCR Amplification kits
      with 32 or 34 PCR cycles. Stutter ratios decreased by an average of 14.7%, 14.9%
      and 18.1% at 100, 50 and 25 pg of template DNA under LT conditions compared with
      those of STD conditions in the Identifiler Kit amplified samples. The LT
      conditions also decreased average stutter ratios by 13.3% compared with those of
      STD conditions in the Identifiler Plus Kit amplified samples. The overall PCR
      efficiency obtained with STD and LT conditions with the two STR kits was
      comparable in terms of the number of detected alleles, peak heights and peak
      height ratios. These results support the hypothesis that a lower temperature
      annealing/extension step reduces the likelihood of slippage during PCR by
      enhancing the stability of the DNA polymerase/template DNA complex or the
      stability of the generated duplex than the conditions of the standard extension
      step. This stability in turn would result in lower stutter ratios.

PMID- 24315612
TI  - Persistence of DNA deposited by the original user on objects after subsequent use
      by a second person.
AB  - There is a paucity of data regarding the persistence of DNA from prior user of an
      object after, its use by another person. To acquire a greater understanding of
      persistence we performed controlled, experiments encompassing over 179 objects
      that had only been used by one individual for an extended, period before used by
      a 2nd person for various but known duration. Our findings show that the profile,
      percentage contribution of the 1st user relative to the 2nd user of an object
      declines in a linear manner, over time. The retrieval of the profile of the
      initial user of the object is dependent on the type of, substrate and use of the
      object. When considering a hard non-porous object the 1st user's profile,
      percentage contribution drops ~50% immediately upon use by a 2nd person and drops
      to ~15% after, 90 min. When considering a soft porous object the 1st wearer's
      profile contribution remains, higher than that of the 2nd wearer during the first
      10h of wear by the 2nd wearer and still, accounts for ~12% after 96 h. This
      substrate associated difference was also observed in an, assessment of a wide
      range of personal objects used by 2nd users for different durations. Particular,
      areas of certain objects were more likely to retain a greater proportion of the
      1st user's DNA than other, areas. Alleles of unknown source were present on the
      majority of objects but rarely exceeded 10% of, the total profile. Greater
      knowledge of persistence will inform investigators regarding the likelihood of,
      detecting a profile of a particular individual based on the type of object and
      its history, and assist with, identifying the best areas of an object to target
      for DNA sampling.

PMID- 24315610
TI  - RNA/DNA co-analysis from human menstrual blood and vaginal secretion stains:
      results of a fourth and fifth collaborative EDNAP exercise.
AB  - The European DNA Profiling Group (EDNAP) organized a fourth and fifth
      collaborative exercise on RNA/DNA co-analysis for body fluid identification and
      STR profiling. The task was to identify dried menstrual blood and vaginal
      secretion stains using specific RNA biomarkers, and additionally test 3
      housekeeping genes for their suitability as reference genes. Six menstrual blood
      and six vaginal secretion stains, two dilution series (1/4-1/64 pieces of a
      menstrual blood/vaginal swab) and, optionally, bona fide or mock casework samples
      of human or non-human origin were analyzed by 24 participating laboratories,
      using RNA extraction or RNA/DNA co-extraction methods. Two novel menstrual blood
      mRNA multiplexes were used: MMP triplex (MMP7, MMP10, MMP11) and MB triplex
      (MSX1, LEFTY2, SFRP4) in conjunction with a housekeeping gene triplex (B2M, UBC,
      UCE). Two novel mRNA multiplexes and a HBD1 singleplex were used for the
      identification of vaginal secretion: Vag triplex (MYOZ1, CYP2B7P1 and MUC4) and a
      Lactobacillus-specific Lacto triplex (Ljen, Lcris, Lgas). The laboratories used
      different chemistries and instrumentation and all were able to successfully
      isolate and detect mRNA in dried stains. The simultaneous extraction of RNA and
      DNA allowed for positive identification of the tissue/fluid source of origin by
      mRNA profiling as well as a simultaneous identification of the body fluid donor
      by STR profiling, also from old and compromised casework samples. The results of
      this and the previous collaborative RNA exercises support RNA profiling as a
      reliable body fluid identification method that can easily be combined with
      current STR typing technology. 

PMID- 24315613
TI  - Comparison of base composition analysis and Sanger sequencing of mitochondrial
      DNA for four U.S. population groups.
AB  - A set of 711 samples from four U.S. population groups was analyzed using a novel
      mass spectrometry based method for mitochondrial DNA (mtDNA) base composition
      profiling. Comparison of the mass spectrometry results with Sanger sequencing
      derived data yielded a concordance rate of 99.97%. Length heteroplasmy was
      identified in 46% of samples and point heteroplasmy was observed in 6.6% of
      samples in the combined mass spectral and Sanger data set. Using discrimination
      capacity as a metric, Sanger sequencing of the full control region had the
      highest discriminatory power, followed by the mass spectrometry base composition
      method, which was more discriminating than Sanger sequencing of just the
      hypervariable regions. This trend is in agreement with the number of nucleotides
      covered by each of the three assays. 

PMID- 24315614
TI  - Understanding Y haplotype matching probability.
AB  - The Y haplotype population-genetic terrain is better explored from a fresh
      perspective rather than by analogy with the more familiar autosomal ideas. For
      haplotype matching probabilities, versus for autosomal matching probabilities,
      explicit attention to modelling - such as how evolution got us where we are - is
      much more important while consideration of population frequency is much less so.
      This paper explores, extends, and explains some of the concepts of "Fundamental
      problem of forensic mathematics - the evidential strength of a rare haplotype
      match". That earlier paper presented and validated a "kappa method" formula for
      the evidential strength when a suspect matches a previously unseen haplotype
      (such as a Y-haplotype) at the crime scene. Mathematical implications of the
      kappa method are intuitive and reasonable. Suspicions to the contrary raised in
      rest on elementary errors. Critical to deriving the kappa method or any sensible
      evidential calculation is understanding that thinking about haplotype population
      frequency is a red herring; the pivotal question is one of matching probability.
      But confusion between the two is unfortunately institutionalized in much of the
      forensic world. Examples make clear why (matching) probability is not
      (population) frequency and why uncertainty intervals on matching probabilities
      are merely confused thinking. Forensic matching calculations should be based on a
      model, on stipulated premises. The model inevitably only approximates reality,
      and any error in the results comes only from error in the model, the inexactness
      of the approximation. Sampling variation does not measure that inexactness and
      hence is not helpful in explaining evidence and is in fact an impediment.
      Alternative haplotype matching probability approaches that various authors have
      considered are reviewed. Some are based on no model and cannot be taken
      seriously. For the others, some evaluation of the models is discussed. Recent
      evidence supports the adequacy of the simple exchangability model on which the
      kappa method rests. However, to make progress toward forensic calculation of Y
      haplotype mixture evidence a different tack is needed. The "Laplace distribution"
      model of Andersen et al. [3] which estimates haplotype frequencies by identifying
      haplotype clusters in population data looks useful.

PMID- 24315615
TI  - The vertical excursion of the body visceral mass during vertical jumps is
      affected by specific respiratory maneuver.
AB  - Most of the inverse modeling of body dynamics in sports assumes that every
      segment is 'rigid' and moves 'as a whole', although we know that uncontrolled
      wobbling masses exist and in specific condition their motion should be optimized,
      both in engineering and biology. The visceral mass movement within the trunk
      segment potentially interferes with respiration and motion acts such as
      locomotion or jumping. The aim of this paper is to refine and expand a previously
      published methodology to estimate that relative motion by testing its ability to
      detect the reduced vertical viscera excursion within the trunk. In fact, a
      respiratory-assisted jumping strategy is expected to limit viscera motion
      stiffening the abdominal content of the bouncing body. Six subjects were
      analyzed, by using inverse dynamics incorporating wobbling masses, during
      repeated vertical jumps performed before and after a specific respiratory
      training period. The viscera excursion, which showed consistent intra-individual
      time courses, decreased by about 30% when the subjects had become familiarized
      with the trunk-stiffening maneuver. We conclude that: (1) present methodology
      proved to detect subtle visceral mass movement within the trunk during repetitive
      motor acts and, particularly, (2) a newly proposed respiratory maneuver/training
      devoted to stiffening the trunk segment can reduce viscera vertical displacement.

PMID- 24315616
TI  - HBV-DNA level at 6 months of entecavir treatment predicts HBeAg loss in HBeAg
      positive chronic hepatitis B patients.
AB  - BACKGROUND/PURPOSE: To evaluate whether on-treatment HBV-DNA level could predict
      the treatment response to entecavir in hepatitis B e antigen (HBe)-positive
      chronic hepatitis B (CHB) patients. METHODS: A total of 68 treatment-naive HBeAg
      positive patients (75% male, mean age at 46.6 +/- 11.9 years) receiving at least
      2 years of entecavir therapy were enrolled. The primary therapeutic endpoint was
      HBeAg loss. On-treatment complete virological response was defined as serum HBV
      DNA < 63 IU/mL. RESULTS: The median baseline alanine aminotransferase (ALT) and
      HBV-DNA levels were 199.5 (27-1622) U/L and 7.7 (3.8-13.2) log10 IU/mL,
      respectively. The median treatment duration was 31.7 (24.3-69.6) months. The rate
      of HBeAg loss at 2 years was 30.9%. By univariate analysis, on-treatment complete
      virological response at Month 6 was associated with HBeAg loss at 2 years (p =
      0.019). After adjustment for age, sex, cirrhosis, baseline ALT, and HBV-DNA
      levels, this factor remained significant in multivariate analysis (odds ratio:
      4.35; 95% confidence interval: 1.24-15.24, p = 0.021). CONCLUSION: On-treatment
      complete virological response at Month 6 is a favorable factor predictive of
      HBeAg loss at 2 years of entecavir therapy. Therefore, measurement of serum HBV
      DNA level at 6 months of entecavir therapy is optimal to predict HBeAg loss at 2
      years of therapy in HBeAg-positive CHB patients.

PMID- 24315617
TI  - Speech disturbances and quality of life in schizophrenia: differential impacts on
      functioning and life satisfaction.
AB  - Speech disturbances in schizophrenia impact on the individual's communicative
      ability. Although they are considered a core feature of schizophrenia,
      comparatively little work has been done to examine their impact on the life
      experiences of patients. This study aimed to examine the relationship between
      schizophrenia speech disturbances, including those traditionally known as formal
      thought disorder (TD), and quality of life (QoL). It assessed effects on
      functioning (objective QoL) and satisfaction (subjective QoL) concurrently, while
      controlling for the influence of neurocognition and depression. Fifty-four
      patients with schizophrenia/schizoaffective disorder were administered the
      MATRICS Consensus Cognitive Battery (MCCB), the PANSS, MADRS (with separate
      ratings for negative TD [verbal underproductivity] and positive TD [verbal
      disorganisation and pressured speech]) and Lehman's QOLI assessing both objective
      and subjective QoL. Ratings of positive and negative TD, depression, and general
      neurocognition were entered into hierarchical regressions to explore their
      relationship with both life functioning and satisfaction. Verbal
      underproductivity was a significant predictor of objective QoL, while pressured
      speech had a trend association with subjective QoL. This suggests a differential
      relationship between speech disturbances and QoL. Verbal underproductivity seems
      to affect daily functioning and relations with others, while pressured speech is
      predictive of satisfaction with life. The impact of verbal underproductivity on
      QoL suggests it to be an important target for rehabilitation in schizophrenia. 

PMID- 24315618
TI  - Child labour must be on the post-2015 agenda.

PMID- 24315619
TI  - Statins, risk assessment, and the new American prevention guidelines.

PMID- 24315621
TI  - The many faces of diabetes: a disease with increasing heterogeneity.
AB  - Diabetes is a much more heterogeneous disease than the present subdivision into
      types 1 and 2 assumes; type 1 and type 2 diabetes probably represent extremes on
      a range of diabetic disorders. Both type 1 and type 2 diabetes seem to result
      from a collision between genes and environment. Although genetic predisposition
      establishes susceptibility, rapid changes in the environment (ie, lifestyle
      factors) are the most probable explanation for the increase in incidence of both
      forms of diabetes. Many patients have genetic predispositions to both forms of
      diabetes, resulting in hybrid forms of diabetes (eg, latent autoimmune diabetes
      in adults). Obesity is a strong modifier of diabetes risk, and can account for
      not only a large proportion of the epidemic of type 2 diabetes in Asia but also
      the ever-increasing number of adolescents with type 2 diabetes. With improved
      characterisation of patients with diabetes, the range of diabetic subgroups will
      become even more diverse in the future. 

PMID- 24315622
TI  - Alcohol consumption and risk of metabolic syndrome: a meta-analysis of
      prospective studies.
AB  - BACKGROUND & AIMS: Epidemiological evidence suggests that alcohol consumption is
      related to the incidence and development of metabolic syndrome. However, data on
      this issue are unstable and controversial. We conducted a meta-analysis to
      provide a quantitative assessment of the association between alcohol intake and
      risk of metabolic syndrome. METHODS: We searched the Pubmed and Embase databases
      up to May 2013 to identify prospective cohort studies related to alcohol
      consumption and metabolic syndrome. Summary effect estimates with 95% confidence
      intervals (CI) were derived using a fixed or random effects model, depending on
      the heterogeneity of the included studies. RESULTS: Six prospective studies
      involving 28,862 participants with 3305 cases of metabolic syndrome were included
      in the meta-analysis. On the basis of the Newcastle Ottawa Scale system, 83.3% of
      the studies were identified as relatively high-quality. In our primary analysis,
      compared with nondrinker, very light drinker was associated with decreased risk
      of metabolic syndrome [pooled relative risk (RR) 0.86, 95% CI: 0.75-0.99, fixed
      effect model] while heavy drinker was associated with increased risk of metabolic
      syndrome (pooled RR 1.84, 95% CI: 1.34-2.52, fixed-effect model). No indications
      of heterogeneity and publication bias were found in these two groups. Estimates
      of total effects were generally consistent in the sensitivity and stratification
      analyses. CONCLUSION: The present meta-analysis of prospective studies suggested
      that heavy alcohol consumption might be associated with an increased risk of
      metabolic syndrome while very light alcohol consumption seemed to be associated
      with a reduced risk of metabolic syndrome.

PMID- 24315623
TI  - New genetic testing in prenatal diagnosis.
AB  - Determining a genetic diagnosis prenatally permits patients to make informed
      reproductive decisions and to be counseled about possible fetal outcomes.
      Therefore, it is important for the provider to be aware of the spectrum of
      genetic conditions and to use appropriate testing modality to obtain specific
      diagnosis. This article reviews genetic techniques available for prenatal
      diagnosis such as preimplantation genetic testing, chromosomal microarray, non
      invasive prenatal screening, and next-generation sequencing. Chromosomal
      microarray has emerged as the first diagnostic test for evaluation of multiple
      congenital anomalies and developmental delay as most of the next-generation
      sequencing methods do not detect copy-number variants (CNVs). Exome sequencing
      and whole genome sequencing are time-consuming, so if this needs to be done to
      obtain an accurate genetic diagnosis, allow sufficient time. 

PMID- 24315624
TI  - Stress amplifications in dental non-carious cervical lesions.
AB  - This study aims to investigate the influence of the presence, shape and depth of
      NCCLs on the mechanical response of a maxillary second premolar subjected to
      functional and non-functional occlusal loadings using 3-D finite element (FE)
      analysis. A three-dimensional model of a maxillary second premolar and its
      supporting bone was constructed based on the contours of their cross-sections.
      From the sound model, cervical defects having either V- or U-shapes, as found
      clinically, were subtracted in three different depths. The models were loaded
      with 105 N to simulate normal chewing forces according to a functional occlusal
      loading (F1) vertically applied and two non-functional loadings (F2 and F3)
      obliquely oriented. Two alveolar bone crest heights were tested. AnsysTM FE
      software was used to compute stress distributions and maximum principal stress
      for each of the models. The presence of a lesion had no effect on the overall
      stress distribution of the system, but affected local stress concentrations. Non
      functional loadings exhibited tensile stresses concentrating at the cervical
      areas and root surfaces, while the functional loading resulted in homogeneous
      stress distributions within the tooth. V-shaped lesions showed higher stress
      levels concentrated at the zenith of the lesion, whereas in U-shaped defect
      stresses concentrated over a wider area. As the lesions advanced in depth, the
      stress was amplified at their deepest part. A trend of stress amplification was
      observed with decreasing bone height. These results suggest a non-linear lesion
      progression with time, with the progression rate increasing with patient's age
      (deeper lesions and lower bone support).

PMID- 24315620
TI  - Pathophysiology and treatment of type 2 diabetes: perspectives on the past,
      present, and future.
AB  - Glucose metabolism is normally regulated by a feedback loop including islet beta
      cells and insulin-sensitive tissues, in which tissue sensitivity to insulin
      affects magnitude of beta-cell response. If insulin resistance is present, beta
      cells maintain normal glucose tolerance by increasing insulin output. Only when
      beta cells cannot release sufficient insulin in the presence of insulin
      resistance do glucose concentrations rise. Although beta-cell dysfunction has a
      clear genetic component, environmental changes play an essential part. Modern
      research approaches have helped to establish the important role that hexoses,
      aminoacids, and fatty acids have in insulin resistance and beta-cell dysfunction,
      and the potential role of changes in the microbiome. Several new approaches for
      treatment have been developed, but more effective therapies to slow progressive
      loss of beta-cell function are needed. Recent findings from clinical trials
      provide important information about methods to prevent and treat type 2 diabetes
      and some of the adverse effects of these interventions. However, additional long
      term studies of drugs and bariatric surgery are needed to identify new ways to
      prevent and treat type 2 diabetes and thereby reduce the harmful effects of this
      disease. 

PMID- 24315625
TI  - Effect of obesity on disease-free and overall survival in node-positive breast
      cancer patients in a large French population: a pooled analysis of two randomised
      trials.
AB  - BACKGROUND: To examine the association between baseline body mass index (BMI),
      and disease-free survival (DFS) and overall survival (OS) in a large French early
      stage breast cancer population included in the UNICANCER Programme d'Action
      Concerte Sein-01 (PACS01) and PACS04 phase III randomised trials. METHODS: After
      a median follow-up of 5.9years, this report analyses 4996 patients with node
      positive breast cancer, and randomly assigned to adjuvant anthracycline-based
      chemotherapy combined or not with taxanes. Univariate analyses were used to study
      the effects of well known prognostic factors and BMI on DFS and OS. BMI was
      obtained at baseline, before chemotherapy initiation, and obesity was defined as
      a BMI?30kg/m(2). Cox proportional hazards regression models were secondly used to
      assess the influence of BMI after adjusting for other factors. Exhaustive
      analysis of the dose intensity delivered was also studied for comparison between
      obese and non-obese patients. RESULTS: Obese patients initially present with more
      advanced disease at diagnosis compared to non-obese patients. By univariate
      analysis, obesity was moderately associated with poorer DFS (hazard ratio
      (HR)=1.18 [1.01-1.39] P=0.04), but mostly with poorer OS (HR=1.38 [1.13-1.69]
      P=0.002). Delivered dose intensity of anthracyclines and taxanes was not
      significantly different between obese and non-obese patients. After adjustment
      for disease characteristics, BMI had no influence either on DFS or OS.
      CONCLUSION: This report suggests that in a French population, obesity has no
      impact on breast cancer prognosis when modern adjuvant chemotherapy, at the
      appropriate dose intensity, is delivered.

PMID- 24315627
TI  - Special issue on conformational selection.

PMID- 24315626
TI  - SH2D4A is frequently downregulated in hepatocellular carcinoma and cirrhotic
      nodules.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
      worldwide. The lack of effective therapeutic options for advanced stage HCCs
      combined with an increasing incidence rate calls for the identification of early
      stage HCC molecular markers. SH2 Domain Containing 4A (SH2D4A) gene maps to human
      chromosome 8p21.3 and encodes for SH(2)A. The chromosomal region containing
      SH2D4A is frequently lost in colorectal, lung and HCC cancers. Our study aimed to
      investigate SH2D4A involvement in HCC pathogenesis combining mRNA expression,
      protein and clinical data. Transcriptome analysis performed on 37 HCC needle
      biopsies (matched with their corresponding non-neoplastic parenchyma) and five
      normal liver donor samples revealed that SH2D4A is downregulated in HCC. Results
      were confirmed by quantitative real-time-polymerase chain reaction (qRT-PCR), 25
      out of 37 (67.6%) fresh frozen samples showed SH2D4A downregulation (p = 0.026).
      Furthermore, combining qRT-PCR and immunohistochemistry data we demonstrated a
      direct correlation between SH2D4A mRNA and SH(2)A protein levels. The analysis of
      a tissue microarray (TMA) containing 336 specimens confirmed that SH(2)A is
      frequently reduced in HCC (56.8%) as well as in cirrhotic nodules (50.5%)
      compared to normal liver samples (31.1%). To conclude, our study revealed that
      SH2D4A is frequently downregulated in HCC samples thus corroborating its putative
      role as a tumour suppressor gene. In addition, we provide new evidence for SH2D4A
      involvement in HCC pathogenesis demonstrating for the first time its deregulation
      in cirrhotic nodules.

PMID- 24315628
TI  - Intracranial supramaximal facial nerve stimulation: a murine model.
AB  - PURPOSE: Supramaximal facial nerve stimulation is an applied current sufficient
      to evoke a maximal electromyographic response of facial musculature. It is used
      during cerebellopontine angle surgery for prognostication of postoperative nerve
      function. We utilized a rat model to examine safe parameters for intracranial
      electrical stimulation. MATERIALS AND METHODS: Intracranial facial nerve
      stimulation with electromyographic monitoring of 14 rats was performed.
      Supramaximal current level was determined and 50 additional pulses of
      supramaximal (4 rats), 3 times supramaximal (4), 10 times supramaximal (3), or
      zero (3) current were applied. To monitor progression of facial nerve injury,
      video recordings of vibrissae movements and eye closure were captured at 1, 3 and
      28 days after surgery; animals were sacrificed on day 28, when nerve morphometry
      was performed. RESULTS: One rat in the supramaximal stimulation group (of 4), and
      one rat in the 10 times supramaximal stimulation group (of 3) demonstrated
      persistent impairment of facial nerve function as evidenced by decreased
      amplitude of vibrissae sweeping and eye closure impairment. The remainder of rats
      in all experimental groups demonstrated symmetric and normal facial nerve
      function at all time points. CONCLUSIONS: A novel animal model for supramaximal
      stimulation of the rat intracranial facial nerve is described. A small proportion
      of animals demonstrated functional evidence of nerve injury postoperatively.
      Function was preserved in some animals after stimulation with current order of
      magnitude higher than supramaximal levels. Further study with this model is
      necessary to definitively isolate the effects of surgical trauma from those of
      supramaximal electrical stimulation.

PMID- 24315630
TI  - When the simple migrated hair results in distressing ear symptoms.
AB  - We present 3 patients who complained of distorted hearing, tinnitus and otalgia
      resulting from scalp and facial hair impacting against the tympanic membrane.
      Removal of the migrated hair with microsuction relieved symptoms immediately. In
      2 cases, the patients had presented to the primary care physician earlier,
      shortly after a haircut. The family physicians had correctly detected the
      migrated hair but failed to identify this as the cause of the patient's symptoms.
      Increased awareness of this potentially common complication will enable the
      family physician to identify and treat these patients in a primary care setting.

PMID- 24315629
TI  - Utility of abdominal imaging to assess for liver metastasis in patients with head
      and neck cancer and abnormal liver function tests.
AB  - PURPOSE: To determine the utility of abdominal imaging to further evaluate
      abnormal pre-operative liver function tests (LFTs) in patients with head and neck
      squamous cell carcinoma (HNSCC). METHODS: Records of patients evaluated by the
      head and neck surgery service from January 2004 through December 2009 were
      reviewed. For patients with abnormal alkaline phosphatase, alanine transaminase,
      or aspartate transaminase, subsequent abdominal imaging was assessed. RESULTS: Of
      the 862 patients with HNSCC who had documented LFTs, 109 (12.6%) had one or more
      abnormal values. In the same time period, LFTs were also obtained on 361 patients
      with benign head and neck tumors; of these, 40 (11.1%) had abnormalities. Of the
      109 patients with HNSCC and abnormal LFTs, 78 (71.6%) underwent abdominal imaging
      (ultrasound, CT, MRI, or PET/CT). Overall, liver metastasis was demonstrated in
      only 1 of 109 patients with abnormal LFTs (0.92%) and in only 1 of 862 patients
      with HNSCC (0.12%). CONCLUSIONS: While HNSCC patients rarely present with liver
      metastasis, they often have abnormal LFTs. Although the presence of liver
      metastasis can dramatically change patient management, the yield of follow-up
      liver imaging for all patients with elevated LFTs is exceedingly low. Thus, the
      use of risk-stratified abdominal imaging may be prudent and cost effective in a
      select group of patients in whom distant metastasis is more likely. However,
      characteristics of this group are difficult to define given the rarity of liver
      metastasis in HNSCC.

PMID- 24315631
TI  - Coated collagen patches for closure of pharyngo-cutaneous fistulas.
AB  - After laryngectomy or lateral pharyngotomy for treatment of laryngeal or
      hypopharyngeal cancer the occurrence of a pharyngo-cutaneous fistula is a
      challenging complication. Especially after previous radiotherapy and expanded
      surgical resections of mucosa the management is demanding. Besides the prolonged
      hospital stay, increased treatment costs and reduced quality of life, a delayed
      adjuvant treatment follows the development of a fistula. Treatment strategies
      range from conservative procedures comprising parenteral nutrition, antibiotics
      and local wound care to primary surgical closure or reconstructive tissue
      transfer. We report three cases of using the fibrin/thrombin-coated collagen
      patch TachoSil((r)) as a solitary or adjuvant strategy in surgical treatment. In
      one patient primary closure of the fistula was achieved by transoral application
      of the collagen patch. In the other cases a not tension free primary suture was
      strengthened by the adjuvant use of TachoSil((r)). The healing process was rapid
      and straightforward in all patients. The use of TachoSil((r)) may be indicated in
      between conservative treatment strategies and reconstructive surgery. After
      occurrence of a fistula the healing process is intended to be accelerated by
      primary closure with TachoSil((r)) or by sealing of a primary suture. 

PMID- 24315632
TI  - A conservative treatment for plastic bronchitis in pediatric age.
AB  - Plastic bronchitis is a rare disorder in pediatric age. This disease can cause
      life-threatening episodes. Broncoscopy plus bronchial lavage is considered the
      gold standard therapeutic technique. Knowledge of this disease is mandatory to
      perform correct diagnosis and provide prompt treatment. The authors report the
      history of a 5-year-old girl affected by plastic bronchitis who was successfully
      treated by a conservative therapy avoiding the traditional more invasive
      management. 

PMID- 24315633
TI  - Surgical techniques for the management of the 'hostile mitral annulus'.
AB  - The mitral annulus can be rendered hostile by several uncommon clinical
      situations such as infective endocarditis, calcification, or previous valve
      surgery. These can all lead to difficulties seating a prosthesis or annuloplasty
      ring. The posterior mitral annulus or anteriorly the intervalvar fibrous body can
      be affected. These situations continue to pose a formidable technical challenge
      to the cardiac surgeon in the operating room. We review the evidence around
      solutions for these problems with the intent of giving surgeons an overview of
      techniques to address these issues. 

PMID- 24315634
TI  - Closure of a broncho-pleural fistula using an atrial septal defect occluder.
AB  - Broncho-pleural fistulae (BPF) are recognised as a rare complication following
      pneumonectomy. We describe a patient, who after failing conservative treatment,
      underwent closure of a persistent fistula with an atrial septal defect (ASD)
      occluder. Additionally we review the literature regarding management of BPF and
      the emerging role of cardiac defect closure devices as a possible treatment
      option. 

PMID- 24315635
TI  - Allergy to heparins, thrombosis, thrombocytopaenia and Kounis syndrome: a
      clinical paradox.

PMID- 24315636
TI  - Forearm instability.
AB  - Forearm instability results from trauma, which disrupts the radial head, the
      interosseous membrane, and the triangular fibrocartilage complex. Inadequate
      treatment of injuries to these forearm stabilizers may result in the complex
      problem of chronic longitudinal forearm instability. Delayed recognition and/or
      treatment of injuries producing forearm dissociation has led to poor patient
      outcomes, which makes timely recognition of the injury pattern imperative. This
      article discusses relevant aspects of forearm anatomy and current concepts in the
      diagnosis and treatment options for this complex injury pattern. 

PMID- 24315637
TI  - CD4(+)and CD8(+)T-cell reactions against leukemia-associated- or minor
      histocompatibility-antigens in AML-patients after allogeneic SCT.
AB  - T-cells play an important role in the remission-maintenance in AML-patients (pts)
      after SCT, however the role of LAA- (WT1, PR1, PRAME) or minor-histocompatibility
      (mHag, HA1) antigen-specific CD4(+) and CD8(+)T-cells is not defined. A LAA/HA1
      peptide/protein stimulation, cloning and monitoring strategy for specific
      CD8(+)/CD4(+)T-cells in AML-pts after SCT is given. Our results show that (1) LAA
      peptide-specific CD8+T-cells are detectable in every AML-pt after SCT. CD8(+)T
      cells, recognizing two different antigens detectable in 5 of 7 cases correlate
      with long-lasting remissions. Clonal TCR-Vbeta-restriction exemplarily proven by
      spectratyping in PRAME-specific CD8(+)T-cells; high PRAME-peptide-reactivity was
      CD4(+)-associated, as shown by IFN-gamma-release. (2) Two types of antigen
      presenting cells (APCs) were tested for presentation of LAA/HA1-proteins to
      CD4(+)T-cells: miniEBV-transduced lymphoblastoid cells (B-cell-source) and CD4
      depleted MNC (source for B-cell/monocyte/DC). We provide a refined cloning-system
      for proliferating, CD40L(+)CD4(+)T-cells after LAA/HA1-stimulation. CD4(+)T-cells
      produced cytokines (GM-CSF, IFN-gamma) upon exposure to LAA/HA1-stimulation until
      after at least 7 restimulations and demonstrated cytotoxic activity against naive
      blasts, but not fibroblasts. Antileukemic activity of unstimulated, stimulated or
      cloned CD4(+)T-cells correlated with defined T-cell-subtypes and the clinical
      course of the disease. In conclusion we provide immunological tools to enrich and
      monitor LAA/HA1-CD4(+)- and CD8(+)T-cells in AML-pts after SCT and generate data
      with relevant prognostic value. We were able to demonstrate the presence of LAA
      peptide-specific CD8(+)T-cell clones in AML-pts after SCT. In addition, we were
      also able to enrich specific antileukemic reactive CD4(+)T-cells without GvH
      reactivity upon repeated LAA/HA1-protein stimulation and limiting dilution
      cloning.

PMID- 24315639
TI  - Cellular antioxidant activity of phenylaminoethyl selenides as monitored by
      chemiluminescence of peroxalate nanoparticles and by reduction of
      lipopolysaccharide-induced oxidative stress.
AB  - Hydrogen peroxide (H2O2), produced in living cells by oxidases and by other
      biochemical reactions, plays an important role in cellular processes such as
      signaling and cell cycle progression. Nevertheless, H2O2 and other reactive
      oxygen species are capable of inducing damage to DNA and other cellular
      components, and oxidative stress caused by overproduction of cellular oxidants
      has been linked to pathologies such as inflammatory diseases and cancer.
      Therefore, new approaches for reducing the accumulation of cellular oxidants are
      of considerable interest from both a biotechnological and a therapeutic
      perspective. Recognizing that selenium is an essential component of the active
      sites of several antioxidant enzymes, we have developed a family of novel
      phenylaminoethyl selenide compounds that are readily taken up into cells and have
      low toxicity in vivo. We now report chemiluminescent imaging of hydrogen peroxide
      consumption by phenylaminoethyl selenides, via the use of peroxalate nanoparticle
      methodology. Further, we demonstrate the ability of phenylaminoethyl selenides to
      decrease lipopolysaccharide-induced oxidative stress in human embryonic kidney
      cells. We also report the successful encapsulation of a phenylaminoethyl selenide
      within poly(lactide-co-glycolide) nanoparticles, and we show that these selenide
      loaded nanoparticles exhibit antioxidant activity in cells. Taken together, these
      results significantly enhance the attractiveness of phenylaminoethyl selenides as
      potential agents for supplementing cellular defenses against reactive oxygen
      species. 

PMID- 24315638
TI  - Significant improvement of thermal stability of glucose 1-dehydrogenase by
      introducing disulfide bonds at the tetramer interface.
AB  - Rational design was applied to glucose 1-dehydrogenase (LsGDH) from
      Lysinibacillus sphaericus G10 to improve its thermal stability by introduction of
      disulfide bridges between subunits. One out of the eleven mutants, designated as
      DS255, displayed significantly enhanced thermal stability with considerable
      soluble expression and high specific activity. It was extremely stable at pH
      ranging from 4.5 to 10.5, as it retained nearly 100% activity after incubating at
      different buffers for 1h. Mutant DS255 also exhibited high thermostability,
      having a half-life of 9900min at 50 degrees C, which was 1868-fold as that of its
      wild type. Moreover, both of the increased free energy of denaturation and
      decreased entropy of denaturation of DS255 suggested that the enzyme structure
      was stabilized by the engineered disulfide bonds. On account of its robust
      stability, mutant DS255 would be a competitive candidate in practical
      applications of chiral chemicals synthesis, biofuel cells and glucose biosensors.

PMID- 24315640
TI  - Identification of a laccase from Ganoderma lucidum CBS 229.93 having potential
      for enhancing cellulase catalyzed lignocellulose degradation.
AB  - Based on a differential pre-screening of 44 white-rot fungi on a lignocellulose
      supplemented minimal medium, four basidiomycetes were selected for further study:
      Ganoderma lucidum, Polyporus brumalis, Polyporus ciliatus and Trametes
      versicolor. Only G. lucidum was able to grow vividly on malt extract or minimal
      media supplemented with alkali lignin. When grown on malt extract or minimal
      medium supplemented with lignocellulose (sugar cane bagasse), the crude G.
      lucidum protein extract exhibited high laccase activity, ~3U/mL toward
      syringaldazine. This activity was 13-17 fold higher than the corresponding
      activities of the crude protein extracts of P. brumalis, P. ciliatus and T.
      versicolor. Native PAGE electrophoresis of the crude G. lucidum extract confirmed
      the presence of an active laccase. The G. lucidum laccase had a molecular weight
      of ~62.5kDa, and a Km value of 0.107mM (determined on ABTS). A partial amino acid
      sequence analysis of four short de novo sequenced peptides, defined after trypsin
      digest analysis using MALDI-TOF MS/MS analysis, revealed 64-100% homology to
      sequences in related laccases in the UniProt database, but also indicated that
      certain sequence stretches had low homology. Addition of the laccase-rich G.
      lucidum broth to lignocellulosic biomass (pretreated sugar cane bagasse) together
      with a state-of-the-art cellulase enzyme preparation (CellicTMCTec1) produced
      significantly increased cellulolytic yields, which were also better than those
      obtained with a T. versicolor laccase addition, indicating that the laccase from
      G. lucidum has unique properties that may be momentous in lignocellulosic biomass
      conversion. 

PMID- 24315641
TI  - Phenylalanine to leucine point mutation in oxyanion hole improved catalytic
      efficiency of Lip12 from Yarrowia lipolytica.
AB  - In lipases, oxyanion hole has crucial role in the stabilisation of enzyme
      substrate complex. Majority of lipases from Yarrowia lipolytica consist of two
      oxyanion hole residues viz.; Thr and Leu. However, Lip12 has Phe instead of Leu
      at second oxyanion hole residue. It was observed that Lip12 has lower specific
      activity and catalytic efficiency than other lipases of Yarrowia. In silico
      analysis of Phe to Leu mutation revealed improved binding energy of Lip12 for p
      np palmitate. This was validated by Phe148 to Leu point mutation where, specific
      activity of mutant was 401U/mg on olive oil, which was two fold higher in
      comparison to wild-type. Kcat, remained unaltered, while decrease in Km was
      predominant for all the substrates used in the study. Improved catalytic
      efficiency of mutant was a function of chain length in case of p-np esters, with
      73% improvement for p-np stearate. However, hydrolysis of triacylglycerides
      improved by 20%, irrespective of chain length. Decrease in activation energy for
      all the substrates, was observed in mutant in comparison to wild-type, indicating
      better stabilisation of transition state complex. Further, unaltered differential
      activation energy for mutant depicts that substrate specificity of enzyme
      remained same after mutation. 

PMID- 24315642
TI  - A specific and rapid colorimetric method to monitor the activity of methionine
      sulfoxide reductase A.
AB  - Considerable evidence indicates that methionine sulfoxide (MetO) reductase A
      (MsrA) plays an important role in cytoprotection against oxidative stress and
      serves as a potential drug target. To screen for MsrA regulators, a rapid and
      specific assay to monitor MsrA activity is required. Most of current assays for
      MsrA activity are based on the reduction of radioactive substrates such as [3H]-N
      acetyl-MetO or fluorescent derivatives such as dimethylaminoazo-benzenesulfonyl
      MetO. However, these assays require extraction procedures and special
      instruments. Here, we developed a specific colorimetric microplate assay for
      testing MsrA activity quickly, which was based on the fact that MsrA can catalyze
      the reduction of methyl sulfoxides and simultaneously oxidize dithiothreitol
      (DTT), whose color can be produced by reacting with Ellman's reagent (dithio-bis
      nitrobenzoic acid, DTNB). The corresponding absorbance change at 412nm was
      recorded with a microplate reader as the reaction proceeded. This method to
      monitor MsrA activity is easy to handle. Our findings may serve as a rapid method
      for the characterization of recombinant enzyme and for the screening of enzyme
      inhibitors, pharmacological activators, gene expression regulators and novel
      substrates. 

PMID- 24315643
TI  - Polymeric macroporous formulations for the control release of mosquitocidal
      Bacillus sphaericus ISPC-8.
AB  - Bio-polymeric mosquitocidal formulations were developed for the control release
      of Bacillus sphaericus ISPC-8 by the immobilization of its spore-crystal complex
      onto the macroporous polymeric matrices. The biodegradable formulations were
      synthesized at sub-zero temperature using natural polymeric substrates like
      agarose, alginate, cellulose, non-adsorbent cotton, wooden cork powder and also
      magnetite nanoparticles. The obtained polymeric matrices were morphologically
      characterized, which showed 85-90% porosity, uniform pores distribution, high
      permeability and controlled degradation (19-30%) in 4 weeks depending upon the
      composition of formulations. Further, the polymeric macroporous formulations were
      tested for persistence of mosquitocidal activity against Culex quinquefasciatus
      larvae. Unformulated B. sphaericus ISPC-8 spores retained 54% of larvicidal
      activity after 7 days, which completely reduced after 35 days of treatment.
      However, the immobilized B. sphaericus spores in agarose-alginate formulations
      showed high larvicidal activity on day 7 and retained about 45% activity even
      after 35 days of treatments. Studies on UV-B and pH dependent inactivation of
      toxins and spore viability showed that these formulations were significantly
      protecting the spores as compared to the unformulated spores, which suggest its
      potential application for the mosquito control program. 

PMID- 24315644
TI  - Improvement of thermal stability of a mutagenised alpha-amylase by manipulation
      of the calcium-binding site.
AB  - Site-directed mutagenesis of an alpha-amylase isolated from Bacillus megaterium
      WHO has been performed to evaluate the roles of the calcium binding site residues
      in enzyme thermostability. The strategy used was to replace residues in the
      hypothetical calcium binding loops of B. megaterium WHO alpha-amylase (BMW
      amylase) by equivalent positions at Halothermothrix orenii alpha-amylase (AmyA)
      as a thermophilic amylase by QuikChange site directed mutagenesis. Asn-75, Ser
      76, and His-77 were mutated in the second calcium binding site which resulted in
      an increase in thermostability. All mutants retained their hydrolytic activity
      although their kcat parameter decreased in compare to the wild type and in the
      presence of calcium ions. In S76P and H77E, the Km for starch decreases while
      overall activity (kcat/Km) was increased. In the presence of calcium, conversion
      of His-77 to Glu resulted in a 4-fold enhancement in enzyme half life and a 9
      degrees C upward shift in T50, which was observed in compare to the wild type.
      Further analysis suggested the H77E mutant as the most stable which increased the
      affinity of the enzyme for calcium ion and its optimum temperature was 5 degrees
      C higher than the wild type. 

PMID- 24315645
TI  - Thermostabilization of extremophilic Dictyoglomus thermophilum GH11 xylanase by
      an N-terminal disulfide bridge and the effect of ionic liquid [emim]OAc on the
      enzymatic performance.
AB  - In the present study, an extremophilic GH11 xylanase was stabilized by an
      engineered N-terminal disulphide bridge. The effect of the stabilization was then
      tested against high temperatures and in the presence of a biomass-dissolving
      ionic liquid, 1-ethyl-3-methylimidazolium acetate ([emim]OAc). The N-terminal
      disulfide bridge increased the half-life of a GH11 xylanase (XYNB) from the
      hyperthermophilic bacterium Dictyoglomus thermophilum by 10-fold at 100 degrees
      C. The apparent temperature optimum increased only by ~5 degrees C, which is less
      than the corresponding increase in mesophilic (~15 degrees C) and moderately
      thermophilic (~10 degrees C) xylanases. The performance of the enzyme was
      increased significantly at 100-110 degrees C. The increasing concentration of
      [emim]OAc almost linearly increased the inactivation level of the enzyme activity
      and 25% [emim]OAc inactivated the enzyme almost fully. On the contrary, the
      apparent temperature optimum did not decrease to a similar extent, and the degree
      of denaturation of the enzyme was also much lower according to the residual
      activity assays. Also, 5% [emim]OAc largely counteracted the benefit obtained by
      the stabilizing disulfide bridge in the temperature-dependent activity assays,
      but not in the stability assays. Km was increased in the presence of [emim]OAc,
      indicating that [emim]OAc interfered the substrate-enzyme interactions. These
      results indicate that the effect of [emim]OAc is targeted more to the functioning
      of the enzyme than the basic stability of the hyperthermophilic GH11 xylanase. 

PMID- 24315646
TI  - Chemical modification of wheat beta-amylase by trinitrobenzenesulfonic acid,
      methoxypolyethylene glycol, and glutaraldehyde to improve its thermal stability
      and activity.
AB  - The amino groups of wheat beta-amylase (WBA) were modified by 2,4,6
      trinitrobenzenesulfonic acid (TNBS), 2,4-bis (O-methoxypolyethylene glycol)-6
      chloro-s-triazine (mPEG), and glutaraldehyde (GA) to improve its thermal
      stability and activity. Modification of WBA by 5mM TNBS, 4.8MUM mPEG and 11 mM GA
      improved its T50 (the temperature at which 50% of its activity is lost after 30
      min of incubation) from 47 +/- 1 degrees C to 48 +/- 2, 55 +/- 2, and 54 +/- 2
      degrees C, respectively. The catalytic activity of WBA was reduced by 15% and 59%
      with modification by 5mM TNBS and 11mM GA, respectively. In all cases, the
      enhancement of thermostability of modified WBA was entropically driven. The
      activity of WBA modified by 4.8MUM mPEG was enhanced by 39% at 25 degrees C.
      Therefore, the thermal stability of WBA was significantly improved by
      modification with mPEG, GA and slightly by TNBS and its catalytic activity was
      enhanced by mPEG.

PMID- 24315647
TI  - Characterization of cellobiose dehydrogenase and its FAD-domain from the
      ligninolytic basidiomycete Pycnoporus sanguineus.
AB  - Cellobiose dehydrogenase (CDH), an extracellular flavocytochrome produced by
      several wood-degrading fungi, was detected in the culture supernatant of the
      selective delignifier Pycnoporus sanguineus maintained on a cellulose-based
      liquid medium. Cellobiose dehydrogenase was purified as two active fractions:
      CDH1-FAD (flavin domain) (40.4 fold) with recovery of 10.9% and CDH1 (flavo-heme
      enzyme) (54.7 fold) with recovery of 9.8%. As determined by SDS-PAGE, the
      molecular mass of the purified enzyme was found to be 113.4kDa and its
      isoelectric point was 4.2, whereas these values for the FAD-domain were 82.7kDa
      and pI=6.7. The carbohydrate content of the purified enzymes was 9.2%. In this
      work, the cellobiose dehydrogenase gene cdh1 and its corresponding cDNA from
      fungus P. sanguineus were isolated, cloned, and characterized. The 2310bp full
      length cDNA of cdh1 encoded a mature CDH protein containing 769 amino acids,
      which was preceded by a signal peptide of 19 amino acids. Moreover, both active
      fractions were characterized in terms of kinetics, temperature and pH optima, and
      antioxidant properties. 

PMID- 24315648
TI  - Enhancement of lipase r27RCL production in Pichia pastoris by regulating gene
      dosage and co-expression with chaperone protein disulfide isomerase.
AB  - Pichia pastoris has been successfully used in the production of many secreted and
      intracellular recombinant proteins, but there is still a large room of
      improvement for this expression system. Two factors drastically influence the
      lipase r27RCL production from Rhizopus chinensis CCTCC M201021, which are gene
      dosage and protein folding in the endoplasmic reticulum (ER). Regarding the
      effect of gene dosage, the enzyme activity for recombinant strain with three
      copies lipase gene was 1.95-fold higher than that for recombinant strain with
      only one copy lipase gene. In addition, the lipase production was further
      improved by co-expression with chaperone PDI involved in the disulfide bond
      formation in the ER. Overall, the maximum enzyme activity reached 355U/mL by the
      recombinant strain with one copy chaperone gene PDI plus five copies lipase gene
      proRCL in shaking flasks, which was 2.74-fold higher than that for the control
      strain with only one copy lipase gene. Overall, co-expression with PDI vastly
      increased the capacity for processing proteins of ER in P. pastoris. 

PMID- 24315649
TI  - Development of immobilized cellulase through functionalized gold nano-particles
      for glucose production by continuous hydrolysis of waste bamboo chopsticks.
AB  - Cellulase immobilized on silica through the assistance of l-cysteine
      functionalized gold nano-particle was applied for the continuous hydrolysis of
      waste bamboo chopsticks powder to produce glucose. The optimal conditions for the
      continuous hydrolysis were pH 8.0, 50 degrees C. A 4-day reaction with an initial
      0.3 gL-1 waste bamboo chopsticks powder, a feed containing 0.2 gL-1 waste bamboo
      chopsticks powder at a continuous feed and draw rate of 0.5 mLmin-1, and an
      enzyme loading of 40 mgcellulase(gsilica)-1, has 72.0-76.6% conversion rates of
      repeated hydrolyses that correspond to a total production of 630.5-671.2mg
      glucose and are much better than batch hydrolyses. At higher enzyme loading (117
      mgcellulase(gsilica)-1), higher initial concentration (0.5 gL-1), and higher feed
      concentration (0.42 gL-1) the conversion rate increases to 82.9% and a total
      amount of 1418 mgglucose. The immobilized cellulase can be recovered easily by
      filtration and used repeatedly at least 6 times over a period more than 90 days
      with a recovered activity approximately the same as or better than previous
      reactions. Thus the process is promising for scaling up.

PMID- 24315651
TI  - Intraoperative ultrasonography of laparoscopic hepatectomy: key technique for
      safe liver transection.

PMID- 24315652
TI  - Application of surgical safety standards to robotic surgery: five principles of
      ethics for nonmaleficence.

PMID- 24315653
TI  - Transapical aortic valve implantation - an Australian experience.
AB  - BACKGROUND: The aim of this study was to report our initial experience with the
      transapical approach to transcatheter aortic valve implantation (TAVI) at an
      Australian institution. METHODS: All patients with severe, symptomatic aortic
      stenosis were assessed by our multidisciplinary team. A total of 32 patients
      received a transapical TAVI using an Edwards SAPIEN prosthesis. Data were
      prospectively collected and analysed according to the Valve Academic Research
      Consortium version 2 guidelines. RESULTS: Intraoperative outcomes included: 100%
      device success with no conversion to surgical valve replacement, extracorporeal
      membrane oxygenation was used electively in 15.6% and emergently in 6.3%, and no
      valve migration or malpositioning requiring prosthesis retrieval and re
      implantation. Outcomes at 30 days post-TAVI included: No mortality, 3.1%
      myocardial infarction, no disabling stroke, 3.1% non-disabling stroke, no
      transient ischaemic attacks, 6.3% life-threatening bleeding, 15.6% major
      bleeding, 3.1% major vascular complications, and 12.5% postoperative acute kidney
      injury requiring renal replacement therapy. Mild paravalvular regurgitation was
      present in 29%, and there was no moderate or severe regurgitation. Mean follow-up
      time was 28.8+/-12.9 months. Cumulative results included: 9.4% mortality, 6.3%
      stroke, 6.3% myocardial infarction, and no repeat procedures. At one year
      postoperation, echocardiography demonstrated that the mean pressure across the
      prosthesis was 10.1+/-1.7mmHg, and the mean aortic valve area was 1.4+/-0.2cm(2).
      CONCLUSION: Good short-term outcomes and low or zero mortality are achievable
      with transapical TAVI at an Australian institution.

PMID- 24315654
TI  - Aortoventriculoplasty for correction of patient-prosthesis mismatch examples.
AB  - OBJECTIVE: Patient-prosthesis mismatch is often considered as an important cause
      of adverse outcome following aortic valve replacement. A small annulus represents
      a challenge for the surgeon; yet can be best managed at the initial operation
      using relatively simple techniques, as later-on correction is often far more
      challenging. Corrective reoperations necessitate drastic root enlargement, along
      with the relief of subvalvular muscular obstruction. PATIENTS AND METHODS: The
      Konno-type aorto-ventriculoplasty is preferred in the present case series in
      order to achieve a radical aortic annulus enlargement in difficult reoperation
      settings and to address the accompanying subvalvular obstruction due to muscular
      hypertrophy simultaneously as well, with the septal patch included in the
      technique. RESULTS: This approach provides satisfactory relief of the obstruction
      at both valvular and subvalvular level and the benefits are immediately evident,
      as symptoms abruptly end in all cases. CONCLUSION: Long-term outcome is also
      excellent in both clinical and haemodynamic terms, as reflected by the
      significant left ventricle mass regression, absence of symptoms and improved
      quality of life.

PMID- 24315655
TI  - IFPA Meeting 2013 Workshop Report II: use of 'omics' in understanding placental
      development, bioinformatics tools for gene expression analysis, planning and
      coordination of a placenta research network, placental imaging, evolutionary
      approaches to understanding pre-eclampsia.
AB  - Workshops are an important part of the IFPA annual meeting as they allow for
      discussion of specialized topics. At the IFPA meeting 2013 twelve themed
      workshops were presented, five of which are summarized in this report. These
      workshops related to various aspects of placental biology but collectively
      covered areas of new technologies for placenta research: 1) use of 'omics' in
      understanding placental development and pathologies; 2) bioinformatics and use of
      omics technologies; 3) planning and coordination of a placenta research network;
      4) clinical imaging and pathological outcomes; 5) placental evolution. 

PMID- 24315656
TI  - An old flame reignites: vagal neuropathy secondary to neurosyphilis.
AB  - OBJECTIVE: This report describes neurosyphilis presenting as vocal fold paresis
      and velopharyngeal incompetence. This represents the first reported case of
      neurosyphilis presenting as a vagal neuropathy since 1963. STUDY DESIGN: Case
      report. METHODS: Review of medical records and literature search. RESULTS: The
      patient presented with voice changes and nasopharyngeal reflux of liquids.
      Examination showed a left vocal fold paresis and moderate velopharyngeal
      incompetence. Laryngeal electromyography revealed evidence of denervation, and
      neurologic evaluation showed bilateral Adie's pupils and a positive CSF VDRL. A
      remote history of syphilis treated with one intramuscular injection was obtained.
      The patient was treated with 6 weeks of penicillin and regained normal vocal
      function with minimal residual intermittent hypernasality. CONCLUSIONS: Given the
      recent increase in the incidence of syphilis in the United States, this case
      serves as a reminder of the importance of including syphilis in the differential
      diagnosis of cranial neuropathies and the increasing likelihood of syphilis
      presenting to otolaryngology and speech pathology practices. Syphilis, a disease
      whose incidence had declined progressively for 60 years in the United States, is
      now resurgent and must be considered in the evaluation of patients presenting
      with unexplained cranial neuropathies.

PMID- 24315657
TI  - Degradation of silicone rubber causes Provox 2 voice prosthesis malfunctioning.
AB  - OBJECTIVE/HYPOTHESIS: Provox 2 voice prosthesis requires periodic replacement due
      to biofilm proliferation which causes malfunctioning of the valve. The aim of
      this study was to show that Provox 2 voice prosthesis malfunctioning is due not
      only to valve obstruction caused by biofilm but also to the silicone variations.
      DESIGN METHODS: Prospective study on the malfunction of Provox2 voice prostheses.
      METHODS: Through photographic and electron microscopic assessment, the authors
      studied nine Provox 2 voice prostheses, which were removed due to malfunctioning.
      RESULTS: Findings revealed that the silicone undergoes a degenerative process,
      thus causing the surface to become rough, deformed, swollen, and translucent.
      Furthermore, electron microscopy confirmed the presence of immune system cells
      and biofilm on the prosthesis surface and their role in creating a structural
      nonhomogenous structure in the silicone, which is deformed due to the presence of
      "crests" caused by material degeneration. CONCLUSION: The degenerative process of
      the silicone seems to be related to the oxygen present in the trachea and
      esophagus and to the production of oxygen-free radicals on the biofilm's part and
      the immune system.

PMID- 24315658
TI  - Prevalence of vocal fry in young adult male American English speakers.
AB  - The purpose of this study was to assess possible gender differences in the
      prevalence of vocal fry in the voices of young male college students. Results
      were compared with previously published findings derived from a matched sample of
      female speakers. Thirty-four male college students, native American English
      speakers, produced speech samples in two speaking conditions: (1) sustained
      isolated vowel /a/ and (2) reading task. Data analyses included perceptual
      evaluations by two licensed speech-language pathologists. Results showed that
      vocal fry was perceived significantly more frequently in sentences than in
      isolated vowel productions. When vocal fry occurred in sentences, it was detected
      significantly more often in sentence-final position than in initial- and/or mid
      sentence position. Furthermore, the prevalence of vocal fry in sentences was
      significantly lower for male speakers than has previously been reported for
      female speakers. Possible physiological and sociolinguistic explanations are
      discussed. 

PMID- 24315659
TI  - Neuromuscular electrical stimulation of the cricothyroid muscle in patients with
      suspected superior laryngeal nerve weakness.
AB  - In this retrospective case study, we report the apparent clinical effectiveness
      of neuromuscular electrical stimulation (NMES) in combination with voice therapy
      (VT) for rehabilitating dysphonia secondary to suspected superior laryngeal nerve
      (SLN) weakness in two female patients. Both patients failed or plateaued with
      traditional VT but had significant improvement with the addition of NMES of the
      cricothyroid muscle and SLN using a VitalStim unit. Stimulation was provided
      simultaneously with voice exercises based on musical phonatory tasks. Both
      acoustic analysis and endoscopic evaluation demonstrated important improvements
      after treatment. In the first patient, the major change was obtained within the
      primo passaggio region; specifically, a decrease in voice breaks was
      demonstrated. In the second patient, an improvement in voice quality (less
      breathiness) and vocal range were the most important findings. Additionally, each
      patient reported a significant improvement in their voice complaints.
      Neuromuscular laryngeal electrical stimulation in combination with vocal
      exercises might be a useful tool to improve voice quality in patients with SLN
      injury. 

PMID- 24315661
TI  - Evaluation of personal health record systems through the lenses of EC research
      projects.
AB  - Personal health record (PHR) systems are a rapidly expanding area in the field of
      health information technology which motivates an ongoing research towards their
      evaluation in several different aspects. In this direction, we present a
      systematic review of the currently available PHR systems. Initially, we define a
      clear and concise set of requirements for efficient PHR systems which is based on
      real-world implementation experiences of several European research projects and
      also on established and widely used formal standards. Subsequently, these
      requirements are used to perform a systematic evaluation of existing PHR system
      implementations. Our evaluation study provides a thorough requirement analysis
      and an insight on the current status of personal health record systems. The
      results of the present work can therefore be used as a basis for future
      evaluation studies which should be conducted periodically as technology evolves
      and requirements are revised. 

PMID- 24315662
TI  - Side-effects of antiepileptic drugs: the economic burden.
AB  - PURPOSE: Antiepileptic drugs are a potentially effective treatment for epilepsy.
      Side-effects are, however, common and the negative consequences necessitate
      treatment ranging from minor interventions to very expensive hospitalization.
      This analysis has been conducted to provide insight into the costs of side
      effects due to antiepileptic drugs in The Netherlands from a societal
      perspective. METHOD: Resources allocated to care (grouped according to health,
      patient and family and other) for five different categories of side-effect were
      measured using a questionnaire. Standard cost prices were derived from the Dutch
      costing manual. Chronic epilepsy patients were invited to complete the
      questionnaire if they had experienced side-effects during the previous 12 months.
      RESULTS: Based on data from 203 patients, the total societal costs of common side
      effects in 2012 are estimated to be ? 20,751 CI:15,049-27,196 (US$26,675
      CI:19,345-34,960) per patient per year. These consist of: health care costs (mean
      ? 4458; US$5731), patient and family costs (i.e. informal care, mean ? 10,526;
      US$13,531) and other costs (i.e. productivity losses, mean ? 5761; US$7406).
      Examining the different categories of side-effects separately, ranging from the
      most to the least expensive category, the cost estimates per patient per year
      were as follows: other (mean ? 13,228; US$17,005), behavioral (mean ? 9689;
      US$12,455), general health (mean ? 7454; US$9582), cognitive (mean ? 7285;
      US$9365) and cosmetic side-effects (mean ? 2845; US$3657). Subgroup analyses
      showed significant differences in costs between patients using monotherapy and
      those using polytherapy when looking at cognitive and cosmetic side-effects.
      CONCLUSION: These estimates should be considered in the overall assessment of the
      economic impact of a pharmacotherapy.

PMID- 24315663
TI  - Effects of oxygen insufflation during pilocarpine-induced status epilepticus on
      mortality, tissue damage and seizures.
AB  - PURPOSE: This prospective, randomized study was performed to investigate the
      effects of oxygen (O2) treatment during sustained epileptic activity on
      mortality, subsequent seizure frequency, and neuronal damage. METHODS: Status
      epilepticus (SE) was induced by intraperitoneal injection of 340mg/kg
      pilocarpine, and terminated by diazepam after 40min. During SE, rats were
      randomized to O2 treatment (insufflation rate of 1.5l/min O2) during SE or normal
      air conditions. Outcome measures were SE-related mortality, seizure occurrence,
      mossy fiber sprouting, neuronal cell loss and expression of 27-kDa heat-shock
      protein (Hsp27). RESULTS: O2-treated and O2-untreated animals did not differ with
      respect to SE latency, diazepam dose required to stop SE. While 7/38 rats died
      during SE in the O2-untreated group, very little mortality (1/38) occurred in the
      O2-treated group (P<0.05). However, within 1h after SE termination, seven O2
      treated rats died which was not observed in the O2-untreated group indicating no
      significant difference in overall mortality. There was a tendency towards lower
      seizure rate in the O2-treated group at one month after pilocarpine-induced SE.
      Three months after SE, however, seizure rates were no longer different between
      both groups. Moreover, mossy fiber sprouting, neuronal cell loss and Hsp27
      expression did not differ between O2-treated and O2-untreated groups. CONCLUSION:
      Our findings indicate that O2 treatment might delay the relative risk of
      epileptic seizures following an initial brain injury, but it may also lead to a
      rather unfavorably increased heterogeneity of epileptogenesis in experimental
      studies.

PMID- 24315660
TI  - Atomic structure from large-area, low-dose exposures of materials: a new route to
      circumvent radiation damage.
AB  - Beam-induced structural modifications are a major nuisance in the study of
      materials by high-resolution electron microscopy. Here, we introduce a new
      approach to circumvent the radiation damage problem by a statistical treatment of
      large, noisy, low-dose data sets of non-periodic configurations (e.g. defects) in
      the material. We distribute the dose over a mixture of different defect
      structures at random positions and with random orientations, and recover
      representative model images via a maximum likelihood search. We demonstrate
      reconstructions from simulated images at such low doses that the location of
      individual entities is not possible. The approach may open a route to study
      currently inaccessible beam-sensitive configurations. 

PMID- 24315664
TI  - 5% CO2 inhalation suppresses hyperventilation-induced absence seizures in
      children.
AB  - Hyperventilation can cause respiratory alkalosis by exhaling CO2, and is often
      used to confirm diagnosis of absence epilepsy. CO2 has long been known for its
      anticonvulsant properties since the 1920s. In this pilot study, we aimed to
      determine whether inhaling medical carbogen containing 5% CO2 and 95% O2 can
      suppress hyperventilation-induced absence seizures and spike-and-wave discharges
      (SWDs). We examined 12 patients whose absence seizures were induced by
      hyperventilation using video electroencephalographic recording for at least 4h.
      The patients were asked to hyperventilate for 3 min while breathing the following
      gases: (1) room air (12 patients); (2) carbogen (12 patients); and (3) 100% O2 (8
      patients). Eight out of twelve patients were also examined in room air through
      pretreatment with carbogen for 3 min before the 3 min hyperventilation. Compared
      with hyperventilation in room air, hyperventilation supplemented with 5% CO2 had
      the following effects: (a) decrease in the number and duration of seizures; (b)
      prolonged appearance of epileptic discharges; and (c) reduction in the number and
      duration of SWDs (P<0.001). However, pretreatment with 5% CO2 and 100% O2
      supplement did not yield similar effects. We demonstrated that 5% CO2 could
      suppress hyperventilation-induced absence seizures and SWDs, supporting the claim
      that 5% CO2 is an effective anticonvulsant agent. Our pilot study provides
      clinical basis that 5% CO2 inhalation could be a therapeutic approach for
      hyperventilation-related seizures.

PMID- 24315665
TI  - TMS, cortical excitability and epilepsy: the clinical impact.
AB  - Paired-pulse transcranial magnetic stimulation (ppTMS) is a well-established
      method for non-invasive measurement of cortical excitability, alterations of
      which are the core background of epilepsy. For the past 20 years this technique
      has been extensively used to assess patients with epilepsy. We present here a
      critical overview of these studies, with emphasis on their translation to the
      clinical practice. 

PMID- 24315667
TI  - Second toe lateral hemipulp flap transfer to cover third toe pulp defect.

PMID- 24315666
TI  - Localized hyperthermia with iron oxide-doped yttrium microparticles: steps toward
      image-guided thermoradiotherapy in liver cancer.
AB  - PURPOSE: To test whether iron oxide (IO)-containing yttrium aluminosilicate (YAS)
      microparticles (MPs) can generate localized therapeutic hyperthermia (>= 43
      degrees C) when injected intratumorally in an animal model of liver cancer and
      whether MP distributions could be visualized with magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: Twenty-one Sprague-Dawley rats implanted with N1
      S1 liver tumors were assigned to alternating magnetic field (AMF) exposure
      following intratumoral injection with IO-YAS MPs (n = 7), sham surgery (n = 7),
      or baseline iron quantification (n = 7). Three fiberoptic probes allowed spatial
      and temporal monitoring of temperatures during 24 minutes of AMF exposure. T2
      weighted turbo spin-echo MR imaging was performed within 1 hour after the
      procedure to detect signal voids caused by IO-YAS deposition. Hematoxylin and
      eosin-stained pathologic slides were also obtained, and the presence of IO-YAS
      was evaluated with inductively coupled plasma optical emission spectroscopy.
      RESULTS: Following AMF exposure, intratumoral temperatures after IO-YAS MP
      injection achieved therapeutic hyperthermia whereas those after sham surgery did
      not (46.6 degrees C +/- 1.3 vs 36.8 degrees C +/- 0.4; P < .0001). Within the
      treated group, the normal hepatic parenchyma (NHP) and rectal temperatures were
      37.4 degrees C +/- 0.9 and 36.5 degrees C +/- 1.0 (P = .0809) at the conclusion
      of AMF exposure, respectively. A T2-weighted signal void at the tumor site was
      observed in all seven treated animals, and intratumoral IO-YAS was visualized on
      subsequent histopathologic examination in each case. The mean ratio of tumor:NHP
      Fe concentrations attributable to IO-YAS MPs was 108:1. CONCLUSIONS: AMF exposure
      of intratumoral IO-YAS MPs generates localized therapeutic hyperthermia in an
      animal model of liver cancer. MR detectability and potential for combination
      brachytherapy warrants further investigation for thermoradiotherapy in liver
      cancer.

PMID- 24315668
TI  - A simple plunger technique for negative pressure during fat harvesting.

PMID- 24315669
TI  - Simultaneous sonication assistance for the synthesis of tetrahydropyridines and
      its efficient catalyst ZrP2O7 nanoparticles.
AB  - In this research, a general synthetic method for the synthesis of
      tetrahydropyridines were developed using ZrP2O7 nanoparticles under ultrasonic
      irradiations. Firstly by a simple and green process, nano zirconium pyrophosphate
      was prepared via sonication. Subsequently, this nanoparticle was used as an
      efficient catalyst for the synthesis of highly functionalized tetrahydropyridines
      via five-component reaction of aromatic aldehyde, amine and ethyl acetoacetate in
      ethanol under ultrasound irradiation. The present approach offers several
      advantages such as high yields, environmentally benign, simple work-up, excellent
      yield of products, short reaction times as well as recoverability and reusability
      of the catalyst. 

PMID- 24315670
TI  - Emulsification by high frequency ultrasound using piezoelectric transducer:
      formation and stability of emulsifier free emulsion.
AB  - Emulsifier free emulsion was developed with a new patented technique for food and
      cosmetic applications. This emulsification process dispersed oil droplets in
      water without any emulsifier. Emulsions were prepared with different vegetable
      oil ratios 5%, 10% and 15% (v/v) using high frequency ultrasounds generated by
      piezoelectric ceramic transducer vibrating at 1.7 MHz. The emulsion was prepared
      with various emulsification times between 0 and 10h. Oil droplets size was
      measured by laser granulometry. The pH variation was monitored; electrophoretic
      mobility and conductivity variation were measured using Zetasizer equipment
      during emulsification process. The results revealed that oil droplets average
      size decreased significantly (p<0.05) during the first 6h of emulsification
      process and that from 160 to 1 MUm for emulsions with 5%, 10% and from 400 to 29
      MUm for emulsion with 15% of initial oil ratio. For all tested oil ratios, pH
      measurement showed significant decrease and negative electrophoretic mobility
      showed the accumulation of OH(-) at oil/water interface leading to droplets
      stability in the emulsion. The conductivity of emulsions showed a decrease of the
      ions quantity in solution, which indicated formation of positive charge layer
      around OH(-) structure. They constitute a double ionic layer around oil particles
      providing emulsion stability. This study showed a strong correlation between
      turbidity measurement and proportion of emulsified oil.

PMID- 24315671
TI  - ED antibiotic use in a developing country.

PMID- 24315672
TI  - Severe sepsis due to cervical abscess after agranulocytosis associated with
      metamizole.

PMID- 24315673
TI  - Comparison of different solid-phase-extraction cartridges for a fatty acid
      cleanup of the ethyl acetate/cyclohexane based multi-pesticide residue method EN
      12393.
AB  - SPE cartridges of different anion exchange materials and florisil were compared
      regarding their efficiency to remove free fatty acids from
      ethylacetate/cyclohexane (1:1) extracts, their elution profiles and recovery
      rates for 38 representative pesticides, their contribution to an elevated
      background during gas chromatography-mass spectrometry (GC-MS), and on possible
      matrix effects caused by the cartridge material itself. From the seven tested
      cartridges, only Varian PSA (PSA) and Silicycle SiliaPrep Diamine (SPD) were very
      well able to retain fatty acids from ethylacetate/cyclohexane solutions and
      provided satisfying recoveries and elution profiles for the tested pesticides.
      Thus, with both cartridges a fast and simple cleanup was developed and tested
      with 86 pesticides as well as with EN 12393 GPC extracts of oat flour. The SPE
      cleanup clearly improved the identification of pesticides and reduced false
      negative findings due to retention time shifts and superimpositions of quantifier
      and/or qualifier ions. As compared with dispersive SPE it was shown, that
      depending on the amount of sorbent the cleanup efficiency was comparable, but
      recoveries were generally better for cartridge SPE procedures. 

PMID- 24315674
TI  - A multi-class bioanalytical methodology for the determination of bisphenol A
      diglycidyl ethers, p-hydroxybenzoic acid esters, benzophenone-type ultraviolet
      filters, triclosan, and triclocarban in human urine by liquid chromatography
      tandem mass spectrometry.
AB  - A liquid-liquid extraction (LLE; ethyl acetate) protocol, followed by liquid
      chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS)
      methodology, was developed for the determination of 19 compounds, including
      bisphenol A diglycidyl ethers (BADGEs; industrial ethers), benzophenone-type UV
      filters (BP-UV filters; precursors and metabolites), p-hydroxybenzoic acid esters
      (parabens; preservatives), triclosan (TCS) and triclocarban (TCC) in human urine.
      Urine specimens were enzymatically deconjugated with beta-glucuronidase (from
      Helix pomatia) and extracted by a LLE procedure for the measurement of total
      concentrations (i.e., free+conjugated forms) of target analytes. Absolute
      recoveries of BADGEs, BP-UV filters, parabens, TCS and TCC ranged 25-135%, 84
      125%, 52-126%, 75-118% and 90-124%, respectively. Method precision (absolute
      values; N=5 replicate analyses at the fortification level of 10 ng, k=5 days)
      ranged from 5.8 (ethyl paraben) to 24.0% (TCS). The limits of quantification
      (LOQs) varied depending on the target compound and generally ranged from 0.2 to
      2.0 ng/mL. The matrix effects ranged from +11 (2,3,4-trihydroxybenzophenone) to 
      86% (2,4-dihydroxybenzophenone). A total of 30 urine specimens collected from
      Athens, Greece, were analyzed for the 19 target compounds to demonstrate the
      applicability of the developed method. The concentrations of target chemicals in
      urine were presented on volume-, specific gravity (SG)-, and creatinine
      normalization bases. MeP, EtP, PrP, OH-EtP, BADGE.2H2O, BP-1 and TCS were found
      frequently in urine at concentrations in the range of 2.7-436 ng/mL, <0.5-25.4
      ng/mL, <0.5-575 ng/mL, <2-18.4 ng/mL, <0.5-13.8 ng/mL, <1-14.6 ng/mL and <0.5
      95.3 ng/mL, respectively.

PMID- 24315675
TI  - On-line miniaturized asymmetrical flow field-flow fractionation-electrospray
      ionization-tandem mass spectrometry with selected reaction monitoring for
      quantitative analysis of phospholipids in plasma lipoproteins.
AB  - A direct analytical method for high speed quantitative analysis of lipids in
      human blood plasma using on-line chip-type asymmetrical flow field-flow
      fractionation-electrospray ionization-tandem mass spectrometry (cAF4-ESI-MS/MS)
      with selected reaction monitoring (SRM) is described in this study. Utilizing a
      miniaturized cAF4 channel, high speed size separation of high density
      lipoproteins (HDL) and low density lipoproteins (LDL) from plasma samples can be
      accomplished at a microflow rate along with simultaneous desalting of
      lipoproteins, both of which are conducive to direct ESI of lipids in
      lipoproteins. This study demonstrates that the SRM method to monitor
      phospholipids during cAF4-ESI-MS/MS can be successfully applied to the
      quantitation of lipid molecules in plasma lipoproteins without the need of a
      separate lipid extraction process. For quantitation of lipids in HDL and LDL
      during cAF4-ESI-MS/MS runs, a protein standard (carbonic anhydrase, 29 kDa) was
      added to each plasma sample as an internal standard such that a peak intensity of
      y67(+5) ions, which are high abundant SRM product ions of CA, could be utilized
      to calculate the relative intensity of each lipid molecule. The developed method
      was applied to plasma samples from 10 patients with coronary artery disease (CAD)
      and 10 healthy control samples, and quantitative analysis of 39 lipid molecules
      including phosphatidylcholines, phosphatidylethanolamines, sphingomyelins,
      phosphatidylglycerols, and phosphatidylinositols, resulted in the selection of 13
      PL species showing more than 2.5 fold difference in relative abundance (p<0.01)
      between the groups. The present study demonstrates a high speed analytical method
      for determining plasma lipid content and distribution without an organic solvent
      extraction of lipids from plasma.

PMID- 24315676
TI  - A chromatographic and computational study on the driving force operating in the
      exceptionally large enantioseparation of N-thiocarbamoyl-3-(4'-biphenyl)-5-phenyl
      4,5-dihydro-(1H) pyrazole on a 4-methylbenzoate cellulose-based chiral stationary
      phase.
AB  - This paper describes the results obtained in the HPLC enantioseparation of N
      thiocarbamoyl-3-(4'-biphenyl)-5-phenyl-4,5-dihydro-(1H) pyrazole on a cellulose
      tris(4-methylbenzoate) chiral stationary phase (OJ-3 CSP) using normal-phase and
      polar organic conditions. The enantioseparation factor (alpha=207) observed using
      the mixture n-hexane-2-propanol 70:30 as a mobile phase is among the highest
      values ever reported in enantioselective HPLC. The enantioseparation process was
      investigated by means of molecular modelling techniques. Chromatographic and
      theoretical investigations addressed the extreme affinity of the most CSP
      retained (S)-enantiomer to the intermolecular H bond network between the ligand
      thioamide group and the stationary phase O atoms. 

PMID- 24315677
TI  - Conventional high-performance liquid chromatography versus derivative
      spectrophotometry for the determination of 1,3,6-pyrenetrisulfonic acid trisodium
      salt and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt in the color additive
      D&C Green No. 8 (Pyranine).
AB  - Specifications in the U.S. Code of Federal Regulations for the color additive D&C
      Green No. 8 (Colour Index No. 59040) limit the levels of the subsidiary colors
      1,3,6-pyrenetrisulfonic acid trisodium salt (P3S) and 1,3,6,8-pyrenetetrasulfonic
      acid tetrasodium salt (P4S). The present paper describes a comparative study of
      two possible methods to replace the currently used multi-step
      TLC/spectrophotometry method of separating and quantifying the minor components
      P3S and P4S in G8. One of the new approaches uses conventional high-performance
      liquid chromatography (HPLC) and the other, derivative spectrophotometry. While
      the derivative spectrophotometric method was shown to be inadequate for the
      analysis of minor components overwhelmed by components of much higher
      concentration, the HPLC method was proven highly effective. The closely related,
      very polar compounds P3S and P4S were separated by the new HPLC method in less
      than 4 min using a conventional HPLC instrument. P3S and P4S were quantified by
      using five-point calibration curves with data points that ranged from 0.45 to
      7.63% and from 0.13 to 1.82%, by weight, for P3S and P4S, respectively. The HPLC
      method was applied to the analysis of test portions from 20 batches of D&C Green
      No. 8 submitted to the U.S. Food and Drug Administration for certification.

PMID- 24315678
TI  - Bifunctional magnetic nanoparticles for analysis of aldehyde metabolites in
      exhaled breath of lung cancer patients.
AB  - We report here the preparation of dual-functionalized magnetic nanoparticles,
      with the nanoparticles as extraction sorbents, a magnetic solid phase extraction
      method was developed and applied for the analysis of trace amount of aldehydes in
      human exhaled breath condensate. In the material, octyl-functionalized internal
      surface provided hydrophobic groups for extraction, non-ionic surfactant (Tween
      20)-coated outer surface offered hydrophilic network structure to prevent the
      access of macromolecules, strong magnetic property of nanoparticles simplified
      the analytical procedure. The experimental results showed that the prepared
      nanoparticles exhibited good dispersibility in aqueous solution and excellent
      extraction efficiency toward aldehydes. Six aldehydes were derivatized with 2,4
      dinitrophenylhydrazine and then the formed hydrazones were extracted by the
      nanoparticles and analyzed by high-performance liquid chromatography-photo diode
      array detector. Under the optimal conditions, the method provided low limits of
      detection (2.9-21.5 nmol L(-1)), satisfactory reproducibility (relative standard
      deviations, 2.9-13.1%) and acceptable recoveries (73.7-133.1%). The developed
      method was applied successfully to determine the aldehydes metabolites in the
      exhaled breath condensate samples of healthy people and lung cancer patients. The
      dual-functionalized material is suitable for biological sample analysis. The
      proposed method provides an alternative approach for quantification of aldehyde
      metabolites in complex biological samples.

PMID- 24315679
TI  - Enantioseparation of racemic trans-delta-viniferin using high speed counter
      current chromatography based on induced circular dichroism technology.
AB  - A preparative chiral high speed counter-current chromatography (HSCCC) method
      based on induced circular dichroism (ICD) spectrum was developed to separate
      trans-delta-viniferin (TVN) enantiomers successfully. The important parameters
      for the chiral HSCCC separation process, including the type of chiral selector
      (CS), the concentration of chiral selector and the equilibrium temperature, were
      optimized using induced circular dichroism spectrum. The final separation
      procedure was established with a biphasic solvent system composed of n-hexane
      ethyl acetate-25 mmol L(-1) hydroxypropyl-beta-cyclodextrin aqueous solution
      (5:5:10, v/v/v) in the head-to-tail elution mode at 5  degrees C. Under optimum
      chiral HSCCC separation conditions, 8.2mg of (7S, 8S)-TVN (1) and 9.4 mg of (7R,
      8R)-TVN (2) were successfully separated from 20mg TVN enantiomers with the purity
      of 99.51% and 99.36%, respectively.

PMID- 24315680
TI  - Multilayer adsorption on fractal surfaces.
AB  - Multilayer adsorption is often observed in liquid chromatography. The most
      frequently employed model for multilayer adsorption is the BET isotherm equation.
      In this study we introduce an interpretation of multilayer adsorption measured on
      liquid chromatographic stationary phases based on the fractal theory. The fractal
      BET isotherm model was successfully used to determine the apparent fractal
      dimension of the adsorbent surface. The nonlinear fitting of the fractal BET
      equation gives us the estimation of the adsorption equilibrium constants and the
      monolayer saturation capacity of the adsorbent as well. In our experiments,
      aniline and proline were used as test molecules on reversed phase and normal
      phase columns, respectively. Our results suggest an apparent fractal dimension
      2.88-2.99 in the case of reversed phase adsorbents, in the contrast with a bare
      silica column with a fractal dimension of 2.54. 

PMID- 24315681
TI  - A GIS based method for soil mapping in Sardinia, Italy: a geomatic approach.
AB  - A new project was recently initiated for the realization of the "Land Unit and
      Soil Capability Map of Sardinia" at a scale of 1:50,000 to support land use
      planning. In this study, we outline the general structure of the project and the
      methods used in the activities that have been thus far conducted. A GIS approach
      was used. We used the soil-landscape paradigm for the prediction of soil classes
      and their spatial distribution or the prediction of soil properties based on
      landscape features. The work is divided into two main phases. In the first phase,
      the available digital data on land cover, geology and topography were processed
      and classified according to their influence on weathering processes and soil
      properties. The methods used in the interpretation are based on consolidated and
      generalized knowledge about the influence of geology, topography and land cover
      on soil properties. The existing soil data (areal and point data) were collected,
      reviewed, validated and standardized according to international and national
      guidelines. Point data considered to be usable were input into a specific
      database created for the project. Using expert interpretation, all digital data
      were merged to produce a first draft of the Land Unit Map. During the second
      phase, this map will be implemented with the existing soil data and verified in
      the field if also needed with new soil data collection, and the final Land Unit
      Map will be produced. The Land Unit and Soil Capability Map will be produced by
      classifying the land units using a reference matching table of land capability
      classes created for this project.

PMID- 24315682
TI  - The effect of tackling on shoulder joint positioning sense in semi-professional
      rugby players.
AB  - OBJECTIVE: To assess the effect of a tackling task replicating the force
      magnitudes and directions seen in a competitive game or training session, on a
      players shoulder joint position sense. DESIGN: Repeated measures design. SETTING:
      Field based. PARTICIPANTS: Nineteen, senior, male, semi-professional rugby union
      players. MAIN OUTCOME MEASURES: Two criterion angles of 45 degrees  and 20
      degrees  off maximal range of shoulder external rotation in the 90 degrees  angle
      of abduction, were assessed for reproduction accuracy prior to, and following a
      field based tackling task against an opponent. A comparison between dominant and
      non-dominant side accuracy was also obtained. RESULTS: Prior to the tackling
      task, joint positioning sense was poorer at the 45 degrees  criterion angle than
      for 20 degrees  off the athletes' maximal range angle. Following the tackling
      task, error scores were significantly increased from baseline measures at the
      outer-range criterion angle for both dominant and non-dominant sides. In contrast
      to previous research the detrimental effect of the task was also greater. In
      addition, there was a significant decrease in accuracy at the 45 degrees 
      criterion angle for the players' non-dominant side. CONCLUSIONS: This study found
      a significant decrease in accuracy of joint position sense following the tackling
      task. It also found this decrease to be greater than previous research findings.
      In contrast to previous studies that found no effect at the 45 degrees  criterion
      angle, this study found significant changes for the players' non-dominant side
      occurred at this angle. A possible explanation for this is that the sensory motor
      system is negatively affected by fatigue and consequently shoulder dynamic
      stability is reduced. This fatigue element explains the trend for increased
      injury frequency in the third quarter of the game and would provide a rationale
      for the inclusion of conditioning programmes that address fatigue resistance and
      motor co-ordination in the region.

PMID- 24315683
TI  - New concepts in restoring shoulder elevation in a stiff and painful shoulder
      patient.
AB  - The treatment and evaluation of a stiff and painful shoulder, characteristic of
      adhesive capsulitis and "frozen" shoulders, is a dilemma for orthopedic
      rehabilitation specialists. A stiff and painful shoulder is all-inclusive of
      Adhesive capsulitis and Frozen Shoulder diagnoses. Adhesive capsulitis and frozen
      shoulder will be referred to as a stiff and painful shoulder, throughout this
      paper. Shoulder motion occurs in multiple planes of movement. Loss of shoulder
      mobility can result in significant functional impairment. The traditional
      treatment approach to restore shoulder mobility emphasizes mobilization of the
      shoulder overhead. Forced elevation in a stiff and painful shoulder can be
      painful and potentially destructive to the glenohumeral joint. This manuscript
      will introduce a new biomechanical approach to evaluate and treat patients with
      stiff and painful shoulders. 

PMID- 24315684
TI  - Polymorphism of growth hormone gene and its association with seminal and sexual
      behavioral traits in crossbred cattle.
AB  - The decline in the male reproductive ability in terms of sexual behavior and
      seminal traits might lead to nonavailability of required number of bulls in a
      progeny testing program. The present study was conducted in 493 crossbred cattle
      (Bos taurus * Bos indicus) bulls to study polymorphisms of growth hormone (GH)
      gene and its association with seminal and sexual behavioral characteristics. A
      428-base pair fragment of GH gene spanning over the fourth exon, fourth intron,
      and fifth exon was amplified and digested with AluI restriction enzyme. Bulls
      were found to be polymorphic, with two variants, LL and LV, and higher genotypic
      frequency for LL being 0.88. Twelve nucleotide changes and a single nonsynonymous
      substitution of Leucine by Valine were observed from GH1 (L) to GH2 (V).
      Statistical analysis revealed that the genotype of the GH gene had a significant
      effect on libido score, reaction time, Flehmen response, requirement of mounting
      stimulus, sperm mass activity, number of semen doses per collection, individual
      fresh sperm motility, postthaw sperm motility, acrosome integrity, hypo-osmotic
      swelling test, live and dead count, total morphological abnormality, and head
      abnormality of sperm in crossbred bulls. Growth hormone gene might be considered
      a candidate gene for seminal and sexual behavioral traits in crossbred cattle. 

PMID- 24315685
TI  - Complex interrelationships among CL, preovulatory follicle, number of follicular
      waves, and right or left ovaries in heifers.
AB  - The diameter of the dominant follicle (DF) of wave 1 was studied on Days 9 to 17
      (Day 0 = ovulation) in a survey of the ipsilateral and contralateral
      relationships between the location of the DF and CL, and number of follicular
      waves per interovulatory interval (IOI). For contralateral relationships,
      regardless of number of waves the diameter of the DF of wave 1 decreased (P <
      0.03) between Days 11 and 13 when referenced to the follicle-CL relationship of
      wave 1 and decreased (P < 0.008) between Days 9 and 11 when referenced to the
      preovulatory follicle (PF)-CL relationship. For wave 2 in two-wave IOIs, the CL
      ovary of ipsilateral relationships had more (P < 0.05) follicles that reached at
      least 6 mm than the non-CL ovary. In three-wave IOIs, frequency of IOIs with the
      DF in the CL ovary was greater (P < 0.02) for wave 2 than for wave 3. In wave 3,
      the preovulatory and the largest subordinate follicles were located more
      frequently (P < 0.005) in the contralateral ovary. Ovulation in two-wave IOIs
      occurred more frequently (P < 0.0009) from the right ovary. In three-wave IOIs
      with a contralateral relationship ovulation occurred more frequently (P < 0.003)
      from the left ovary; a negative intraovarian effect of the CL on location of the
      PF may account for more ovulations from the left ovary and a reported greater
      frequency of the contralateral relationship. The hypothesis was supported that
      the ipsilateral versus contralateral relationship between the PF and CL is
      affected by the DF-CL relationship during the previous follicular waves and by
      the number and identity of waves per IOI. 

PMID- 24315686
TI  - Dynamic reprogramming of 5-hydroxymethylcytosine during early porcine
      embryogenesis.
AB  - DNA active demethylation is an important epigenetic phenomenon observed in
      porcine zygotes, yet its molecular origins are unknown. Our results show that 5
      methylcytosine (5mC) converts into 5-hydroxymethylcytosine (5hmC) during the
      first cell cycle in porcine in vivo fertilization (IVV), IVF, and SCNT embryos,
      but not in parthenogenetically activated embryos. Expression of Ten-Eleven
      Translocation 1 (TET1) correlates with this conversion. Expression of 5mC
      gradually decreases until the morula stage; it is only expressed in the inner
      cell mass, but not trophectoderm regions of IVV and IVF blastocysts. Expression
      of 5mC in SCNT embryos is ectopically distinct from that observed in IVV and IVF
      embryos. In addition, 5hmC expression was similar to that of 5mC in IVV cleavage
      stage embryos. Expression of 5hmC remained constant in IVF and SCNT embryos, and
      was evenly distributed among the inner cell mass and trophectoderm regions
      derived from IVV, IVF, and SCNT blastocysts. Ten-Eleven Translocation 3 was
      highly expressed in two-cell embryos, whereas TET1 and TET2 were highly expressed
      in blastocysts. These data suggest that TET1-catalyzed 5hmC may be involved in
      active DNA demethylation in porcine early embryos. In addition, 5mC, but not
      5hmC, participates in the initial cell lineage specification in porcine IVV and
      IVF blastocysts. Last, SCNT embryos show aberrant 5mC and 5hmC expression during
      early porcine embryonic development. 

PMID- 24315688
TI  - POU transcription factors in melanocytes and melanoma.
AB  - Re-activation of molecules active in embryogenesis can play an important role in
      cancer, since they can provide tumor cells with malignant properties. Several
      members of the family of POU transcription factors are essential for the
      development of the nervous system and several are expressed in the neural crest,
      which is the same location where melanocytic cells develop from. Here, the POU
      transcription factor family and its role in melanocytic transformation and
      melanoma are reviewed. 

PMID- 24315689
TI  - Effective myofibroblast dedifferentiation by concomitant inhibition of TGF-beta
      signaling and perturbation of MAPK signaling.
AB  - Fibrotic diseases are a group of pathologies with high incidence and mortality.
      Despite extensive research efforts, effective therapies are still not available.
      Understanding the molecular mechanisms driving the onset, progression and
      possible resolution of fibrosis is a prerequisite to the development of
      successful therapies. The central role of the TGF-beta pathway and myofibroblasts
      in the pathogenesis of fibrosis is now generally accepted. The possible
      mechanisms of myofibroblast elimination or dedifferentiation, on the other hand,
      are still almost uncharted territory. Here we show that sustained expression of
      some components of MAPK signaling pathway (PDGFB, Ha-Ras(G12V) or the
      transcription factor EGR4) in primary chicken embryo dermal myofibroblasts
      results in a loss of autocrine TGF-beta signaling and suppression of the
      myofibroblastic phenotype, characterized by the loss of alpha smooth muscle actin
      fibers and a substantial reduction in the production of extracellular matrix.
      Detailed analysis of the possible molecular mechanisms employed by EGR4 revealed
      FOXG1, BAMBI, NAB1, NAB2 and DUSP5 genes forming an EGR4 regulated network
      counteracting autocrine TGF-beta signaling. We have also found that a combination
      of chemical inhibition of TGF-beta signaling and perturbation of MAPK signaling
      with phorbol ester mimics the anti-fibrotic effects of PDGFB, Ha-Ras(G12V) and
      EGR4. 

PMID- 24315687
TI  - Progesterone to prevent spontaneous preterm birth.
AB  - Preterm birth is the leading cause of perinatal morbidity and mortality
      worldwide, and its prevention is an important healthcare priority. Preterm
      parturition is one of the 'great obstetrical syndromes' and is caused by multiple
      etiologies. One of the mechanisms of disease is the untimely decline in
      progesterone action, which can present as a clinically silent sonographic short
      cervix in the midtrimester. The detection of a short cervix in the midtrimester
      is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce
      the rate of preterm delivery by 45% and the rate of neonatal morbidity (admission
      to the neonatal intensive care unit, respiratory distress syndrome, need for
      mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth
      <33 weeks of gestation, 11 patients with a short cervix would need to be treated
      (based on an individual patient meta-analysis). Vaginal progesterone reduces the
      rate of spontaneous preterm birth in women with a short cervix, both with and
      without a prior history of preterm birth. In patients with a prior history of
      preterm birth, vaginal progesterone is as effective as cervical cerclage to
      prevent preterm delivery. 17alpha-Hydroxyprogesterone caproate has not been shown
      to be effective in reducing the rate of spontaneous preterm birth in women with a
      short cervix. 

PMID- 24315690
TI  - AP-1/c-Jun transcription factors: regulation and function in malignant melanoma.
AB  - Malignant melanoma is an aggressive form of skin cancer with an increasing
      incidence worldwide. One way to address the pathology of the disease is through
      molecular research. In addition to the analysis of melanoma-relevant signaling
      pathways, the investigation of important transcription factors is a fundamental
      objective. The AP-1 transcription factor family is known to play an important
      role in melanoma progression and development. The AP-1 family member c-Jun is
      highly expressed and active in melanoma cells, and the mechanisms and signaling
      pathways regulating c-Jun protein are diverse. In addition to the common
      regulation and activation of c-Jun by mitogen-activated protein kinases (MAPKs),
      there are several other signaling pathways and interactions leading to c-Jun
      protein expression and thus AP-1 activation. In malignant melanoma, and many
      other cancer types, c-Jun has mainly oncogenic functions; however, other AP-1
      proteins also have anti-oncogenic roles. Interestingly, several studies have
      revealed that a strong AP-1 activity in melanoma mainly depends on c-Jun.
      Recently, it has also been shown that the c-Jun protein is regulated and
      activated by several other mechanisms, including miRNAs and the cytoskeleton. In
      summary, there are a variety of mechanisms underlying the induction of c-Jun
      protein expression and activity leading to tumor progression and development, and
      this diverse regulatory machinery is due to the heterogeneity of different tumor
      types, particularly in malignant melanoma. 

PMID- 24315691
TI  - The action of two ethyl carbamates on acetylcholinesterase and reproductive
      organs of Rhipicephalus microplus.
AB  - The effects produced by the new synthetic carbamates ethyl-(4-bromophenyl)
      carbamate and ethyl-(4-chlorophenyl) carbamate on the acetylcholinesterase (AChE)
      activity, egg structure and reproductive organs of two Rhipicephalus microplus
      strains were evaluated. Inhibition kinetic parameters showed that the studied
      carbamates are weak inhibitors and have a low affinity for R. microplus AChE.
      Histologically, in oocytes from carbamate-treated engorged female ticks, a loss
      of shape, cytoplasmic vacuoles, decreased chorion deposition, alterations in
      cytoplasmic granularity and irregular membranes were observed. In oocyte germinal
      vesicles, a loss of shape, nucleolar fragmentation and membrane alterations with
      degenerative signs were observed. The ovarian epithelium was vacuolated,
      flattened, eroded and contained pyknotic nuclei. These alterations were observed
      from the first day and persisted and increased in severity until day 7 post
      treatment. The ovaries from carbamate-treated ticks had fewer stage IV-V oocytes
      and more stage I-II oocytes. Additionally, eggs produced by the treated ticks had
      a modified appearance, decreased size, a reduced superficial waxy layer and a
      loss of viability. The results of this study show that the effects of carbamates
      on R. microplus were independent of AChE inhibition and show that the
      morphological alterations in the reproductive organs were due to carbamate
      actions on the vitellogenesis and viability of the ovarian cells.

PMID- 24315692
TI  - Effect of new ethyl and methyl carbamates on Rhipicephalus microplus larvae and
      adult ticks resistant to conventional ixodicides.
AB  - The effects of six new synthetic carbamates on fully engorged females of four
      Rhipicephalus microplus strains (one reference strain susceptible to conventional
      ixodicides, two strains multiresistant to ixodicides and one tick field isolate)
      were compared. In addition, the effect of two other new synthetic carbamates was
      tested on larvae from the same strains. The first six tested carbamates reduced
      egg laying and inhibited egg hatching in the four studied strains (P<0.05).
      Compared with untreated females, the eggs produced by the treated engorged female
      ticks of all strains had a dark, dry, opaque appearance and were less adherent.
      The remaining two tested carbamates induced larval mortality in all of the
      evaluated strains. The three studied R. microplus strains displayed 50%
      resistance ratios (RR50) of less than 2 when compared to the susceptible
      reference strain. These results demonstrate that both carbamates with a
      larvicidal effect and carbamates that inhibit egg laying and embryo development
      are efficacious against tick strains that are resistant to commercial ixodicides,
      no cross resistance was observed. 

PMID- 24315693
TI  - Vector-borne pathogens in dogs from Costa Rica: first molecular description of
      Babesia vogeli and Hepatozoon canis infections with a high prevalence of
      monocytic ehrlichiosis and the manifestations of co-infection.
AB  - Infection with canine vector-borne pathogens was evaluated in dogs from four
      different regions of Costa Rica by PCR. Demographic data, clinical signs, packed
      cell volume values, and the presence of tick infestation were recorded for each
      dog. Forty seven percent (69/146) of the dogs were infected with at least one
      pathogen and 12% were co-infected with two pathogens. Ehrlichia canis was
      detected in 34%, Anaplasma platys in 10%, Babesia vogeli in 8%, and Hepatozoon
      canis in 7.5% of the blood samples. No infection was detected with Leishmania
      spp. in blood, skin scrapings or conjunctival swabs. Thirty percent of the dogs
      presented at least one clinical sign compatible with vector-borne disease, and of
      those, 66% were infected with a pathogen. Subclinical infections were determined
      in 58% of the infected dogs including 82% (9/11), 58% (29/50), 42% (5/12) and 36%
      (5/14) of the dogs with H. canis, E. canis, B. vogeli and A. platys infections,
      respectively. A distinct relationship was found between infection and anemia. The
      mean PCV values were 34.4% in dogs with no infection, 31.5% in those who had a
      single infection and 23% in those with co-infection. Co-infected dogs had
      significantly lower PCV values compared to non-infected and single-infected dogs
      (p<0.0001). Thirty five percent (51/146) of the dogs were infested with ticks,
      82% of them were infested with Rhipicephalus sanguineus sensu lato and 18% with
      Amblyomma ovale. Dogs infected with A. platys, B. vogeli, or E. canis were
      significantly associated with R. sanguineus s.l. infestation (p<0.029). This is
      the first description of infections with B. vogeli and H. canis in Costa Rica as
      well as in Central America. The results of this study indicate that multiple
      vector-borne pathogens responsible for severe diseases infect dogs in Costa Rica
      and therefore, increased owner and veterinarian awareness are needed. Moreover,
      prevention of tick infestation is recommended to decrease the threat of these
      diseases to the canine population.

PMID- 24315694
TI  - Pharmacological knowledge and sustainable anthelmintic therapy in ruminants.
AB  - Considering the increasing concern for the development of anthelmintic
      resistance, the use of pharmacology-based information is critical to design
      successful strategies for the future of parasite control in livestock. Integrated
      evaluation of the available knowledge on pharmacological features is required to
      optimize the activity and to achieve sustainable use of the existing anthelmintic
      drugs. The assessment of the drug disposition in the host and the comprehension
      of the mechanisms of drug influx/efflux/detoxification in different target
      helminths, has signified a relevant progress on the understanding of the
      pharmacology of anthelmintic drugs in ruminant species. However, additional
      scientific knowledge on how to improve the use of available and novel molecules
      is required to avoid/delay resistance development. Different pharmacokinetic
      based approaches to enhance parasite exposure and the use of mixtures of drugs
      from different chemical families have been proposed as valid strategies to delay
      the development of anthelmintic resistance. The rationale behind using drug
      combinations is based on the fact that individual worms may have a lower degree
      of resistance to a multiple component formulation (each chemical with different
      mode of action/resistance) compared to that observed when a single anthelmintic
      is used. However, the limited available information is unclear on the potential
      additive or synergistic effects occurring after co-administration of two (or
      more) drugs with different mode of action. This review article contributes to the
      topic with some pharmacology-based data emerging from the assessment of combined
      anthelmintic preparations. The activity against multi-drug-resistant isolates
      based on novel modes of action is a highly favorable element to judge the future
      of some of the recently developed anthelmintic compounds. More specific knowledge
      on the basic host-parasite kinetic behavior as well as a highly responsible use
      of those novel compounds will be necessary to secure their maximum lifespans.
      Overall, the outcome from integrated pharmaco-parasitological research approaches
      has greatly contributed to optimize drug activity, which seems relevant to
      preserve existing and particularly novel active ingredients as useful tools for
      parasite control in livestock animals. 

PMID- 24315695
TI  - Clinical significance of serum triple monoclonal components: a report of 6 cases
      and a review of the literature.
AB  - A serum multiple monoclonal component (MC) is very rare. We here report 6
      patients with 3 MCs. The triple MC was detected in all of them by immunofixation.
      2/6 patients did not present hematological or oncological associated disease,
      while in the remaining 4, Waldenstrom macroglobulinaemia (2 cases), Polycythemia
      Vera and non-Hodgkin lymphoma were diagnosed. Of the 49 global patients reported
      in the literature (6+43), 64.6% had a lymphoproliferative disorder and only in 3
      cases there was no associated disease. Therefore, the detection of such
      laboratory evidence should propel physicians to a deeper investigation. 

PMID- 24315696
TI  - Discussion.

PMID- 24315697
TI  - Totally thoracoscopic closure of ventricular septal defect without a robotically
      assisted surgical system: a summary of 119 cases.
AB  - OBJECTIVES: To summarize the clinical outcomes of totally thoracoscopic closure
      of a ventricular septal defect (VSD). METHODS: Totally thoracoscopic VSD closure
      was performed in 119 patients (66 boys; mean age, 7.1 +/- 3.6 years). An
      additional 35 patients undergoing open-chest VSD closure were selected as a
      control group. Using 3 port incisions in the right chest, pericardiotomy, bicaval
      occlusion, atriotomy, and VSD closure were performed by thoracoscopy without the
      aid of a robotically assisted surgical system. RESULTS: Cardiopulmonary bypass
      and aortic crossclamp times were 42.2 +/- 9.8 and 32.5 +/- 7.3 minutes,
      respectively. There were no deaths but 1 patient required insertion of a
      permanent pacemaker as a result of postoperative atrioventricular conduction
      block. The length of stay in the intensive care unit (11.0 +/- 2.6 vs 22.9 +/-
      4.9 hours, P < .01) or postoperative hospital stay (4.2 +/- 1.1 vs 6.6 +/- 2.1
      days, P < .03) in the thoracoscopic group were shorter than in the control group.
      The percentage of patients who required postoperative opioid analgesics in the
      thoracoscopic group was lower than in the control group (31.9% vs 74.2%, P <
      .001). Rate of blood transfusion during the operation (17.6% vs 65.7%, P = .001)
      and the postoperative use of opioid analgesics (31.9% vs 74.3%, P = .003) in the
      thoracoscopic group was lower than in the control group. Transesophageal
      echocardiographic analysis 4.6 +/- 2.3 months after the operation showed complete
      closure of the defect. CONCLUSIONS: Totally thoracoscopic closure of VSD through
      a 3-port entry was safe and effective.

PMID- 24315698
TI  - External cephalic version - the bad, the good and the what now?

PMID- 24315699
TI  - Transoesophageal Doppler-guided fluid management in massive obstetric
      haemorrhage.
AB  - Massive postpartum haemorrhage is a major worldwide cause of maternal mortality.
      Management requires intensive fluid resuscitation and blood transfusion. Although
      fluid therapy is often directed by the results of a full blood count and clotting
      screen, recent technological advances allow monitoring of haemodynamic function
      and cardiac output. Transoesophageal Doppler technology has been used during
      haemorrhagic shock in non-obstetric patients. We present the case of a caesarean
      delivery complicated by massive haemorrhage where transoesophageal Doppler
      monitoring with the CardioQ-ODMTM was used to guide fluid therapy and the use of
      vasoactive drugs. 

PMID- 24315700
TI  - An exemplar of model-based cognitive neuroscience.
AB  - Are categories learned by forming abstract prototypes or by remembering specific
      exemplars? Mack, Preston, and Love observed that patterns of functional MRI
      (fMRI) brain activity were more consistent with patterns of representations
      predicted by exemplar models than by prototype models. Their work represents the
      theoretical power of emerging approaches to model-based cognitive neuroscience. 

PMID- 24315701
TI  - Modeling total maximum allocated loads for heavy metals in Jinzhou Bay, China.
AB  - With the recent development of society and economy in the cities of Huludao and
      Jinzhou, Liaoning Province, China, environment and ecosystem problems have become
      increasingly serious in Jinzhou Bay, China, because of the increasing amount of
      heavy metal pollutants being discharged. To solve these problems, a water quality
      model of heavy metals coupled with a 3D hydrodynamic model is constructed to
      estimate the environmental capacity (EC) and total maximum allocated loads
      (TMALs) for Zn and Cd of three river catchments in Jinzhou Bay. According to the
      model, the ECs for Zn and Cd are approximately 17 and 8 tons per month,
      respectively, if the criterion obtained from HC5 values (fifth percentile of the
      SSD) is set as the control criterion (8.24 MUg/L for Zn and 3.83 MUg/L for Cd) in
      Jinzhou Bay, and the TMALs of the three river catchments are 4 and 1.7 tons per
      month.

PMID- 24315702
TI  - Young green turtles, Chelonia mydas, exposed to plastic in a frontal area of the
      SW Atlantic.
AB  - Ingestion of anthropogenic debris represents an important threat to marine turtle
      populations. Information has been limited to inventories of debris ingested and
      its consequences, but why ingestion occurs and the conditions that enable it are
      less understood. Here we report on the occurrence of plastic ingestion in young
      green turtles (Chelonia mydas) inhabiting the Rio de la Plata (SW Atlantic). This
      estuarine area is characterized by a frontal system that accumulates
      anthropogenic debris. We explored exposure of green turtles to plastic and its
      ingestion via debris distribution, habitat use and digestive tract examination.
      Results indicated that there is considerable overlap of frontal accumulated
      plastic and core foraging areas of the animals. Exposure results in ingestion, as
      shown by the high frequency of plastic found in the digestive tracts. The Rio de
      la Plata estuarine front is an area of conservation concern for young green
      turtles. 

PMID- 24315703
TI  - Feasibility study of FDG PET/CT-derived primary tumour glycolysis as a prognostic
      indicator of survival in patients with non-small-cell lung cancer.
AB  - AIM: To assess the feasibility and prognostic value of measuring total lesion
      glycolysis of the primary tumour (TLG(primary)) using combined 2-[18F]-fluoro-2
      deoxy-d-glucose (FDG) positron-emission tomography/computed tomography (PET/CT)
      in patients with proven or suspected non-small-cell lung cancer (NSCLC) in the
      routine diagnostic setting. MATERIALS AND METHODS: At the All wales Research and
      Diagnostic Positron Emission Tomography Centre in Cardiff (PETIC), in the
      calendar year 2011, 288 consecutive patients were identified with a single
      pulmonary mass in whom NSCLC was confirmed or clinically diagnosed following
      multidisciplinary team review. In a retrospective analysis, for each patient the
      PET-derived volume of the primary tumour and SUVMEAN was calculated using
      adaptive thresholds of 40% and 50% of the SUVMAX of the primary tumour. The
      TLG(primary) (calculated by volume x SUVMEAN) was calculated at these two
      thresholds and was used to predict survival in a multivariate analysis with TNM
      (tumour, node, metastasis) stage, age, sex, and SUV(MAX). The primary endpoint
      was overall survival over a minimum follow-up of at least 7 months. RESULTS: In
      virtually every case, the primary tumour could be measured using the automated
      software with minimal use of manual adjustments. In multivariate analysis, TNM
      clinical stage, log(TLG(primary)) and sex were independent predictors of overall
      survival. CONCLUSION: Measurements of primary tumour total lesion glycolysis are
      simple to perform and provide additional prognostic information over and above
      that provided by TNM staging.

PMID- 24315704
TI  - Re: Kenneth G. Nepple, Andrew J. Stephenson, Dorina Kallogjeri, et al. Mortality
      after prostate cancer treatment with radical prostatectomy, external-beam
      radiation therapy, or brachytherapy in men without comorbidity. Eur Urol
      2013;64:372-8.

PMID- 24315705
TI  - What are the implications of the surgical learning curve?

PMID- 24315706
TI  - Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular
      function following radical prostatectomy for clinically localized prostate
      cancer.
AB  - Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy
      (RP). We conducted a randomized controlled trial to examine the efficacy of
      aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men
      (n=25 per group) after RP. AT consisted of five walking sessions per week at 55
      100% of peak oxygen uptake (VO2peak) for 30-60 min per session following a
      nonlinear prescription. The primary outcome was change in the prevalence of ED,
      as measured by the International Index of Erectile Function (IIEF), from baseline
      to 6 mo. Secondary outcomes were brachial artery flow-mediated dilation (FMD),
      VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition),
      and patient-reported outcomes (PROs). The prevalence of ED (IIEF score <= 21)
      decreased by 20% in the AT group and by 24% in the UC group (difference:
      p=0.406). There were no significant between-group differences in any erectile
      function subscale (p>0.05). Significant between-group differences were observed
      for changes in FMD and VO2peak, favoring AT. There were no group differences in
      other markers of CV risk profile or PROs. In summary, nonlinear AT does not
      improve ED in men with localized prostate cancer in the acute period following
      RP. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00620932.

PMID- 24315707
TI  - Reply to Michael Froehner's letter to the editor re: Kenneth G. Nepple, Andrew J.
      Stephenson, Dorina Kallogjeri, et al. Mortality after prostate cancer treatment
      with radical prostatectomy, external-beam radiation therapy, or brachytherapy in
      men without comorbidity. Eur Urol 2013;64:372-8.

PMID- 24315708
TI  - Exercise as treatment for androgen deprivation therapy-associated physical
      dysfunction: ready for prime time?

PMID- 24315710
TI  - Transtibial prosthesis suspension systems: systematic review of literature.
AB  - BACKGROUND: Today a number of prosthetic suspension systems are available for
      transtibial amputees. Consideration of an appropriate suspension system can
      ensure that amputee's functional needs are satisfied. The higher the insight to
      suspension systems, the easier would be the selection for prosthetists. This
      review attempted to find scientific evidence pertaining to various transtibial
      suspension systems to provide selection criteria for clinicians. METHODS:
      Databases of PubMed, Web of Science, and ScienceDirect were explored to find
      related articles. Search terms were as follows: "Transtibial prosthesis (32),
      prosthetic suspension (48), lower limb prosthesis (54), below-knee prosthesis
      (58), prosthetic liner (20), transtibial (193), and prosthetic socket (111)". Two
      reviewers separately examined the papers. Study design (case series of five or
      more subjects, retrospective or prospective), research instrument, sampling
      method, outcome measures and protocols were reviewed. FINDINGS: Based on the
      selection criteria, 22 articles (15 prospective studies, and 7 surveys) remained.
      Sweat control was found to be a major concern with the available suspension
      liners. Donning and doffing procedures for soft liners are also problematic for
      some users, particularly those with upper limb weakness. Moreover, the total
      surface bearing (TSB) socket with pin/lock system is favored by the majority of
      amputees. INTERPRETATION: In summary, no clinical evidence is available to
      suggest what kind of suspension system could have an influential effect as a
      "standard" system for all transtibial amputees. However, among various suspension
      systems for transtibial amputees, the Iceross system was favored by the majority
      of users in terms of function and comfort.

PMID- 24315711
TI  - Lower-extremity kinematics and postural stability during stair negotiation:
      effects of two cognitive tasks.
AB  - BACKGROUND: Concurrent cognitive tasks were found to affect gait characteristics
      during level walking, such as decreasing speed, cadence, step length, etc. Given
      that many accidents occur during stair negotiation and people often perform
      cognitive tasks concurrently with stair negotiation in daily life, there is a
      need to study how cognitive tasks affect gait characteristics and postural
      stability during stair negotiation. This study aimed to determine cognitive task
      effects on lower-extremity kinematics and postural stability during stair
      negotiation. We also examined the difference in cognitive demands between ascent
      and descent. METHODS: Two cognitive tasks, i.e. 'backward digit recall' and
      'counting backward in threes', were examined. There were three testing conditions
      corresponding to a baseline and the two cognitive tasks, respectively. In the
      baseline, no cognitive task was performed. In the cognitive task conditions, the
      cognitive task was performed continuously throughout the stair negotiation trial.
      Each participant performed six ascent trials and six descent trials under each
      testing condition. We measured the cognitive task performance. Lower-extremity
      kinematics and postural stability were calculated using the data collected from a
      complete stair gait cycle that was obtained for the dominant leg. FINDINGS: In
      general, concurrent cognitive tasks had adverse effects on lower-extremity
      kinematics and postural stability during both ascent and decent. No differences
      in dependent measures were found between cognitive tasks. Additionally, ascent
      and descent appeared to be equally cognitively demanding. INTERPRETATION: The
      findings from this study can help better understand inadequate postural reactions
      due to cognitive load that may cause stair accidents.

PMID- 24315709
TI  - Effect of alignment changes on socket reaction moments while walking in
      transtibial prostheses with energy storage and return feet.
AB  - BACKGROUND: Energy storage and return feet are designed for active amputees.
      However, little is known about the socket reaction moments in transtibial
      prostheses with energy storage and return feet. The aim of this study was to
      investigate the effect of alignment changes on the socket reaction moments during
      gait while using the energy storage and return feet. METHODS: A Smart PyramidTM
      was used to measure the socket reaction moments in 10 subjects with transtibial
      prostheses while walking under 25 alignment conditions, including a nominal
      alignment (as defined by conventional clinical methods), as well as angle
      malalignments of 2 degrees , 4 degrees  and 6 degrees  (flexion, extension,
      abduction, and adduction) and translation malalignments of 5mm, 10mm and 15mm
      (anterior, posterior, lateral, and medial) referenced from the nominal alignment.
      The socket reaction moments of the nominal alignment were compared with each
      malalignment. FINDINGS: Both coronal and sagittal alignment changes demonstrated
      systematic effects on the socket reaction moments. In the sagittal plane, angle
      and translation alignment changes demonstrated significant differences (P<0.05)
      in the minimum moment, the moment at 45% of stance and the maximum moment for
      some comparisons. In the coronal plane, angle and translation alignment changes
      demonstrated significant differences (P<0.05) in the moment at 30% and 75% of
      stance for all comparisons. INTERPRETATION: The alignment may have systematic
      effects on the socket reaction moments in transtibial prostheses with energy
      storage and return feet. The socket reaction moments could potentially be a
      useful biomechanical parameter to evaluate the alignment of the transtibial
      prostheses.

PMID- 24315712
TI  - Complication rates associated with levonorgestrel intrauterine system use in
      adolescents with developmental disabilities.
AB  - STUDY OBJECTIVE: To assess the complication rates with the use of the
      levonorgestrel intrauterine system (LNG IUS) in adolescents with developmental
      disabilities. DESIGN: Retrospective chart review of all adolescents with
      developmental disabilities taken to the operating room for LNG IUS insertion
      between January 2000 and July 2009 at the Royal Children's Hospital, Melbourne,
      Australia. Cases identified from the surgical database, and medical records
      reviewed. MAIN OUTCOME MEASURES: Complication rates with LNG IUS use in
      adolescents with development disabilities: non-insertion, uterine perforation,
      infection, and expulsion. RESULTS: Fifty-six adolescents with developmental
      disabilities had an attempted LNG IUS insertion. The average age at insertion was
      15.6 years (range 10.5-21.5 y). The LNG IUS was used as first line therapy in 14
      cases (25%). Pre-insertion ultrasonography was ordered in 48% of cases, out of
      which 5 cases had uterine lengths <6 cm. Despite this, 4 of these cases had
      successful insertions. Two insertion attempts were abandoned intra-operatively
      (3.6%); one due to inadequate uterine length of 4 cm, and the other due to
      anatomic distortion. One spontaneous expulsion occurred at approximately 5 months
      (1.9%). Four IUDs were removed prematurely (7.4% withdrawal rate); 1 for
      persistent abdominal pain, 1 for irregular bleeding, and 2 for suspected
      malpositions. There were no documented cases of infection, perforation, or
      pregnancy. CONCLUSION: Our experience in this population has been very positive
      and confirms that complication rates are comparable to that in adults.

PMID- 24315713
TI  - Partnering with public schools: a resident-driven reproductive health education
      initiative.
AB  - STUDY OBJECTIVES: To assess the impact of a resident-driven sexual health
      educational initiative in an inner-city Cleveland middle school. DESIGN, SETTING,
      AND PARTICIPANTS: 10 resident physicians and 57 students in 7(th) and 8(th) grade
      participated in this prospective cohort study. INTERVENTIONS AND MAIN OUTCOME
      MEASURES: Residents taught 3 sessions on the topics of basic anatomy and
      physiology, pregnancy, sexually transmitted infections (STI), contraception, and
      safe relationships. Outcome measures included the percentages of students able to
      name at least 3 different STIs and contraceptive methods; to name potential
      complications of STIs; and to correctly identify condoms and abstinence as the
      only contraceptive methods also protective against STI transmission. RESULTS:
      Significant improvements were noted in students' baseline knowledge of human
      anatomy, contraception, and safe sex practices after completion of the
      curriculum. The percentage of students able to name at least 3 forms of birth
      control increased from 1.7% to 70.7% (P < .0001). The percentage able to name at
      least 3 different STIs increased from 5.3% to 72.4% (P < .0001). Follow-up
      testing 4 months after completion of the curriculum demonstrated significant
      knowledge retention. All residents and medical students surveyed described a
      perceived need for comprehensive-rather than abstinence-based-reproductive health
      education in schools. CONCLUSIONS: The socioeconomic burden of teen pregnancy
      justifies comprehensive efforts to improve reproductive health education.

PMID- 24315714
TI  - Retrospective review of norethindrone use in adolescents.
AB  - STUDY OBJECTIVE: Our objectives were to review norethindrone use in an adolescent
      population in a tertiary care center and to assess the effectiveness of the
      norethindrone taper in the management of acute heavy menstrual bleeding in
      adolescents. DESIGN: Retrospective cohort study. SETTING: Tertiary care center.
      PARTICIPANTS: 176 adolescent females prescribed norethindrone 0.35 mg between
      July 2007 and September 2010. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Discontinuation and irregular bleeding rates. RESULTS: Mean age was 14.8 +/- 2.3
      years. Most common indication for use was heavy menstrual bleeding (32.9%). Most
      common reasons for use of a progestin only pill were neurologic (27.8%) and
      cardiovascular diseases (17.6%). Discontinuation rate was 48.5%, most commonly
      for irregular bleeding (54.5%). Irregular bleeding and systemic side effects were
      associated with discontinuation (P = .006 and .003 respectively). No serious
      adverse events were reported. Twenty patients required norethindrone taper for
      heavy bleeding; of this group 78.9% experienced complete cessation of bleeding
      within 7 days. CONCLUSIONS: Our findings support use of norethindrone as an
      effective alternative among adolescents with contraindications to administration
      of estrogen and for whom control of acute heavy menstrual bleeding is desired.

PMID- 24315715
TI  - Adolescents' and young women's use of a microbicide surrogate product when
      receiving oral sex.
AB  - STUDY OBJECTIVE: Genital herpes, which can be spread through oral sex, is an
      important target for microbicides. We examined episode-specific predictors of
      young women's receptive oral sex and of microbicide surrogate use. DESIGN:
      Longitudinal study. SETTING: Participants were recruited to participate in a
      microbicide acceptability study from adolescent clinics and local colleges and
      through snowballing. PARTICIPANTS: Young women (ages 14 to 21 y) who reported
      sexual contact on at least 1 weekly phone interview (n = 181) were included from
      the larger sample of 208 young women. MAIN OUTCOME MEASURES: On weekly diary
      phone interviews, participants reported whether or not their last sexual contact
      included receptive oral sex and whether or not their last sexual contact included
      use of a microbicide surrogate. RESULTS AND CONCLUSIONS: Participants reported a
      total of 1042 episodes of sexual contact of which 311 included receptive oral sex
      and 354 included microbicide surrogate use. Being older, having sex for the first
      time with a partner, and having given oral sex were associated with having
      received oral sex during a sexual episode. Being older, being African American,
      and having discussed the microbicide surrogate with their partner were associated
      with having used the microbicide surrogate use during a sexual episode. These
      results indicate that oral sex should be considered in the design of clinical
      trials. Future studies need to evaluate ways to promote consistent microbicide
      use in the context of receiving oral sex as well as those factors (eg, taste,
      pleasure) which may serve as a barrier.

PMID- 24315716
TI  - Association between maternal preventive care utilization and adolescent
      vaccination: it's not just about Pap testing.
AB  - STUDY OBJECTIVE: To examine the association between maternal preventive care
      utilization and human papillomavirus (HPV) vaccine uptake by their adolescent
      daughters. DESIGN: A cross-sectional study using immunization records from
      administrative claims and the state health department's immunization information
      system from June 2006 through May 2011. PARTICIPANTS: Commercially-insured
      Michigan females aged 13-17 in May 2011 and their mothers. Mothers were
      identified using relationship information on the insurance contract. MAIN OUTCOME
      MEASURES: Using logistic regression, we investigated whether initiating and/or
      completing the HPV vaccine series were associated with maternal preventive care
      utilization (Papaniculou testing, mammograms, primary care office visits)
      independently and using a combined maternal preventive care utilization index.
      RESULTS: Among 38,604 mother-daughter pairs, 36% of daughters initiated and 22%
      completed the HPV vaccine series. Maternal utilization of each recommended
      service was modestly associated with both daughter's initiation and completion of
      the HPV vaccine. Effect estimates for receipt of Papaniculou test on vaccine
      initiation (OR = 1.07, 95% CI = 1.06-1.08) were not any higher than for
      mammograms (OR = 1.10, 95% CI = 1.08-1.11) or primary care office visits (OR =
      1.07, 95% CI = 1.06-1.09). Using a maternal preventive care utilization index,
      vaccine uptake increased with an increasing number of received services.
      CONCLUSIONS: Maternal receipt of recommended preventive care, which may reflect
      general attitudes toward prevention, is as or more predictive of daughter's
      vaccination status than cervical cancer screening alone. Engaging women in broad
      routine preventive care practices may have additional positive effects on
      adolescent HPV vaccination beyond those achieved through cervical cancer
      prevention efforts alone.

PMID- 24315718
TI  - Evolution of basal joint arthroplasty and technology in hand surgery.
AB  - There are many surgical procedures that provide pain relief and improve function
      for trapeziometacarpal (TM) arthritis. The aim of this article is to review the
      history of surgical treatment of thumb basal joint arthritis and to discuss some
      of the recent advances based on evolving technology. Our preferred treatment is
      described, and explanation provided for why we have avoided the temptation to
      change to the "latest and greatest" treatment for this condition.

PMID- 24315717
TI  - Evidence of allelic imbalance in the schizophrenia susceptibility gene ZNF804A in
      human dorsolateral prefrontal cortex.
AB  - The rs1344706, an intronic SNP within the zinc-finger protein 804A gene
      (ZNF804A), was identified as one of the most compelling risk SNPs for
      schizophrenia (SZ) and bipolar disorder (BD). It is however not clear by which
      molecular mechanisms ZNF804A increases disease risk. We evaluated the role of
      ZNF804A in SZ and BD by genotyping the originally associated rs1344706 SNP and an
      exonic SNP (rs12476147) located in exon four of ZNF804A in a sample of 422 SZ,
      382 BD, and 507 controls from the isolated population of the Costa Rica Central
      Valley. We also investigated the rs1344706 SNP for allelic specific expression
      (ASE) imbalance in the dorsolateral prefrontal cortex (DLPFC) of 46 heterozygous
      postmortem brains. While no significant association between rs1344706 and SZ or
      BD was observed in the Costa Rica sample, we observed an increased risk of SZ for
      the minor allele (A) of the exonic rs12476147 SNP (p=0.026). Our ASE assay
      detected a significant over-expression of the rs12476147 A allele in DLPFC of
      rs1344706 heterozygous subjects. Interestingly, cDNA allele ratios were
      significantly different according to the intronic rs1344706 genotypes (p
      value=0.03), with the rs1344706 A allele associated with increased ZNF804A
      rs12476147 A allele expression (average 1.06, p-value=0.02, for heterozygous
      subjects vs. genomic DNA). In conclusion, we have demonstrated a significant
      association of rs12476147 with SZ, and using a powerful within-subject design, an
      allelic expression imbalance of ZNF804A exonic SNP rs12476147 in the DLPFC.
      Although this data does not preclude the possibility of other functional variants
      in ZNF804A, it provides evidence that the rs1344706 SZ risk allele is the cis
      regulatory variant directly responsible for this allelic expression imbalance in
      adult cortex. 

PMID- 24315719
TI  - Follicular dendritic cells: origin, phenotype, and function in health and
      disease.
AB  - Follicular dendritic cells (FDCs) were originally identified by their specific
      morphology and by their ability to trap immune-complexed antigen in B cell
      follicles. By virtue of the latter as well as the provision of chemokines,
      adhesion molecules, and trophic factors, FDCs participate in the shaping of B
      cell responses. Importantly, FDCs also supply tingible body macrophages (TBMs)
      with the eat-me-signaling molecule milk fat globule-EGF factor 8 (Mfge8), thereby
      enabling the disposal of apoptotic B cells. Recent studies have provided
      fundamental insights into the multiple functions of FDCs in both physiological
      and pathophysiological contexts and into their origin. Here we review these
      findings, and discuss current concepts related to FDC histogenesis both in
      lymphoid organs and in inflammatory lymphoneogenesis. 

PMID- 24315720
TI  - The effect of cilostazol on carotid intima-media thickness progression in
      patients with symptomatic intracranial atherosclerotic stenosis.
AB  - BACKGROUND: The progression of carotid intima-media thickness (CIMT) is closely
      associated with ischemic stroke recurrence. However, the efficacy of cilostazol
      on preventing CIMT progression in stroke patients has never been investigated
      properly by a prospective trial. METHODS: This study is a part of "Trial of
      Cilostazol in Symptomatic Intracranial Arterial Stenosis-2." Six centers that are
      available to measure CIMT according to the protocol participated in this
      substudy. After 7 months of randomization, the changes of CIMT were compared
      between cilostazol group and clopidogrel group. CIMT was measured by a
      semiautomated software (Intimascope) and was presented as the mean of maximum
      (CIMT-max) and average (CIMT-ave) of both common carotid arteries. Linear
      logistic regression analysis and analysis of covariance were performed to verify
      the independent factors associated with CIMT progression. RESULTS: Among the 85
      patients, 39 subjects were assigned to cilostazol group and 46 subjects to
      clopidogrel group. Follow-up CIMT significantly decreased in cilostazol group
      (CIMT-max: -.03 +/- .11 and CIMT-ave: -.02 +/- .08) compared with the increase in
      clopidogrel group (CIMT-max: .04 +/- .20 and CIMT-ave: .04 +/- .11; P = .05 and P
      = .04, respectively). Female, diabetes, and smoking were independently associated
      with the progression of CIMT, whereas the use of cilostazol was against CIMT
      progression from the results of linear regression analysis (P = .03 for both CIMT
      max and CIMT-ave). The use of cilostazol also well predicted less progression of
      CIMT at follow-up after adjusting for baseline CIMT values and conventional risk
      factors (CIMT-max: P = .04 and CIMT-ave: P = .03). CONCLUSION: Cilostazol has a
      beneficial effect in preventing the progression of CIMT in ischemic stroke
      patients.

PMID- 24315722
TI  - To close or not to close.

PMID- 24315721
TI  - The impact of World and European Football Cups on stroke in the population of
      Dijon, France: a longitudinal study from 1986 to 2006.
AB  - BACKGROUND: Acute stress may trigger vascular events. We aimed to investigate
      whether important football competitions involving the French football team
      increased the occurrence of stroke. METHODS: We retrospectively retrieved data of
      fatal and nonfatal stroke during 4 World Football Cups (1986, 1998, 2002, and
      2006) and 4 European Championships (1992, 1996, 2000, and 2004), based on data
      from the population-based Stroke Registry of Dijon, France. One period of
      exposure was analyzed: the period of competition extended to 15 days before and
      after the competitions. The number of strokes was compared between exposed and
      unexposed corresponding periods of preceding and following years using Poisson
      regression. RESULTS: A total of 175 strokes were observed during the exposed
      periods compared with 192 and 217 strokes in the unexposed preceding and
      following periods. Multivariate regression analyses showed an overall 30%
      significant decrease in stroke numbers between periods of competition and
      unexposed periods of following year (risk ratio (RR) = 1.3; 95% confidence
      interval [CI] = 1.0-1.6; P = .029) but not with that of preceding year (RR = 1.1;
      95% CI = .9-1.3; P = .367). This was mostly explained by a 40% decrease in stroke
      numbers during European Championships, compared with the unexposed following
      periods (RR = 1.4; 95% CI = 1.0-1.9; P = .044) in stratified analyses by football
      competitions. CONCLUSIONS: Watching European football competitions had a positive
      impact in the city of Dijon with a decrease of stroke numbers. European
      championship is possibly associated with higher television audience and long
      lasting euphoria although other factors may be involved. Further studies using
      nationwide data are recommended to validate these findings.

PMID- 24315723
TI  - Thyrotoxic periodic paralysis: diversity in America.
AB  - BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening
      complication of thyrotoxicosis, characterized by hypokalemia and muscle
      paralysis. OBJECTIVE: TPP, although becoming more prevalent in western countries,
      is still often not recognized due to lack of familiarity and the subtlety of the
      thyrotoxic symptoms. Early recognition by emergency physicians can prevent
      potential mortality. CASE REPORT: A 23-year-old Vietnamese male presented with a
      2-h history of complete flaccid quadriplegia and chest tightness. Electrolyte
      studies revealed a critical potassium level of 1.4 mmol/L. The patient was
      admitted to the intensive care unit where further workup revealed thyrotoxicosis
      and the patient was subsequently diagnosed with TPP. CONCLUSIONS: TPP should
      always be considered as a differential in patients, especially in young males of
      Asian descent with lower-limb paralysis or weakness. We present this case,
      followed by a review of the literature.

PMID- 24315724
TI  - Comparison of the efficacy and safety of new oral anticoagulants with warfarin in
      patients with atrial fibrillation: a meta-analysis of randomised trials.
AB  - BACKGROUND: Four new oral anticoagulants compare favourably with warfarin for
      stroke prevention in patients with atrial fibrillation; however, the balance
      between efficacy and safety in subgroups needs better definition. We aimed to
      assess the relative benefit of new oral anticoagulants in key subgroups, and the
      effects on important secondary outcomes. METHODS: We searched Medline from Jan 1,
      2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of
      patients with atrial fibrillation who were randomised to receive new oral
      anticoagulants or warfarin, and trials in which both efficacy and safety outcomes
      were reported. We did a prespecified meta-analysis of all 71,683 participants
      included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The
      main outcomes were stroke and systemic embolic events, ischaemic stroke,
      haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding,
      intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative
      risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess
      whether differences in patient and trial characteristics affected outcomes. We
      used a random-effects model to compare pooled outcomes and tested for
      heterogeneity. FINDINGS: 42,411 participants received a new oral anticoagulant
      and 29,272 participants received warfarin. New oral anticoagulants significantly
      reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0.81,
      95% CI 0.73-0.91; p<0.0001), mainly driven by a reduction in haemorrhagic stroke
      (0.49, 0.38-0.64; p<0.0001). New oral anticoagulants also significantly reduced
      all-cause mortality (0.90, 0.85-0.95; p=0.0003) and intracranial haemorrhage
      (0.48, 0.39-0.59; p<0.0001), but increased gastrointestinal bleeding (1.25, 1.01
      1.55; p=0.04). We noted no heterogeneity for stroke or systemic embolic events in
      important subgroups, but there was a greater relative reduction in major bleeding
      with new oral anticoagulants when the centre-based time in therapeutic range was
      less than 66% than when it was 66% or more (0.69, 0.59-0.81 vs 0.93, 0.76-1.13; p
      for interaction 0.022). Low-dose new oral anticoagulant regimens showed similar
      overall reductions in stroke or systemic embolic events to warfarin (1.03, 0.84
      1.27; p=0.74), and a more favourable bleeding profile (0.65, 0.43-1.00; p=0.05),
      but significantly more ischaemic strokes (1.28, 1.02-1.60; p=0.045).
      INTERPRETATION: This meta-analysis is the first to include data for all four new
      oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke
      prevention or systemic embolic events in patients with atrial fibrillation. New
      oral anticoagulants had a favourable risk-benefit profile, with significant
      reductions in stroke, intracranial haemorrhage, and mortality, and with similar
      major bleeding as for warfarin, but increased gastrointestinal bleeding. The
      relative efficacy and safety of new oral anticoagulants was consistent across a
      wide range of patients. Our findings offer clinicians a more comprehensive
      picture of the new oral anticoagulants as a therapeutic option to reduce the risk
      of stroke in this patient population. FUNDING: None.

PMID- 24315725
TI  - Warfarin or novel oral anticoagulants for atrial fibrillation?

PMID- 24315726
TI  - Palestinian health research.

PMID- 24315727
TI  - Progress of The Lancet Palestinian Health Alliance.

PMID- 24315729
TI  - Latent Toxoplasma gondii infection leads to deficits in goal-directed behavior in
      healthy elderly.
AB  - Goal-directed behavior is well-known to show declines in elderly individuals,
      possibly because of alterations in dopaminergic neural transmission. The
      dopaminergic system is modulated by a number of other different factors. One of
      these factors, which has attracted a considerable amount of interest in
      neurobiology, but has only rarely been examined with respect to its possible
      modulatory role for cognitive functions in elderly individuals, is latent
      Toxoplasma gondii (T. gondii) infection. Latent T. gondii infection may be of
      relevance to goal-directed behavior as it alters dopaminergic neural
      transmission. We examine goal-directed behavior in T. gondii IgG positive and
      negative elderly subjects in auditory distraction paradigm. We apply event
      related potentials to examine which cognitive subprocesses are affected by latent
      T. gondii infection on a neurophysiological level. We show that latent T. gondii
      infection compromises the management of auditory distraction in elderly by
      specifically delaying processes of attentional allocation and disengagement. The
      results show that latent T. gondii infection is neglected but an important
      neurobiological modulator of cognitive functions in elderly individuals. 

PMID- 24315728
TI  - Age and duration of inflammatory environment differentially affect the
      neuroimmune response and catecholaminergic neurons in the midbrain and brainstem.
AB  - Neuroinflammation and degeneration of ascending catecholaminergic systems occur
      early in the neurodegenerative process. Age and the duration of a pro
      inflammatory environment induced by continuous intraventricular
      lipopolysaccharide (LPS) differentially affect the expression profile of pro- and
      anti-inflammatory genes and proteins as well as the number of activated microglia
      (express major histocompatibility complex II; MHC II) and the integrity and
      density of ascending catecholaminergic neural systems originating from the locus
      coeruleus (LC) and substantia nigra pars compacta (SNpc) in rats. LPS infusion
      increased gene expression and/or protein levels for both pro- and anti
      inflammatory biomarkers. Although LPS infusion stimulated a robust increase in IL
      1beta gene and protein expression, this increase was blunted with age. LPS
      infusion also increased the density of activated microglia cells throughout the
      midbrain and brainstem. Corresponding to the development of a pro-inflammatory
      environment, LC and SNpc neurons immunopositive for tyrosine-hydroxylase (the
      rate-limiting synthetic enzyme for dopamine and norepinephrine) decreased in
      number, along with a decrease in tyrosine-hydroxylase gene expression in the
      midbrain and/or brainstem region. Our data support the concept that continuous
      exposure to a pro-inflammatory environment drives exaggerated changes in the
      production and release of inflammatory mediators that interact with age to impair
      functional capacity of the SNpc and LC. 

PMID- 24315730
TI  - Perceived symptoms and the supportive care needs of breast cancer survivors six
      months to five years post-treatment period.
AB  - PURPOSE: This study characterized the range and levels of perceived symptoms and
      unmet needs reported by breast cancer survivors in the half-year to five year
      post-treatment period, and determined whether the symptoms can be a predictor of
      unmet needs. METHODS: In a cross-sectional study, 150 breast cancer survivors
      (mean age: 55.1 +/- 8 years) at the half-year to five year post-treatment period
      were enrolled for analysis. The measuring scales used included the Memorial
      Symptom Assessment Scale (MSAS), and the Supportive Care Needs Survey Short Form
      (SCNS-SF34). RESULTS: 88% of the survivors reported having at least one symptom,
      while 51% reported at least one unmet need. Lack of energy was the most prevalent
      symptom (47%), followed by numbness/tingling in hands/feet (41%). Most of the
      survivors had unmet needs in the Health care system/Information domain (37%
      reported at least one unmet need for help), followed by Psychological needs
      (29%). The mean scores for the SCNS-SF34 domains, except for sexuality, were
      significantly higher in the high-symptom group (mean 17.6-32.2) compared with the
      low-symptom group (mean 3.5-22.3) (p < 0.01). Regression of the SCNS-SF34 domain
      scores against the MSAS scores revealed an increase in the explained variance of
      from 14% to 54%. CONCLUSION: Our results suggest that breast cancer survivors
      continue to experience a multitude of symptoms, and the burden of symptoms may be
      associated with unmet needs across a range of domains.

PMID- 24315731
TI  - Procedural learning deficits in specific language impairment (SLI): a meta
      analysis of serial reaction time task performance.
AB  - Meta-analysis and meta-regression were used to evaluate whether evidence to date
      demonstrates deficits in procedural memory in individuals with specific language
      impairment (SLI), and to examine reasons for inconsistencies of findings across
      studies. The Procedural Deficit Hypothesis (PDH) proposes that SLI is largely
      explained by abnormal functioning of the frontal-basal ganglia circuits that
      support procedural memory. It has also been suggested that declarative memory can
      compensate for at least some of the problems observed in individuals with SLI. A
      number of studies have used Serial Reaction Time (SRT) tasks to investigate
      procedural learning in SLI. In this report, results from eight studies that
      collectively examined 186 participants with SLI and 203 typically-developing
      peers were submitted to a meta-analysis. The average mean effect size was .328
      (CI95: .071, .584) and was significant. This suggests SLI is associated with
      impairments of procedural learning as measured by the SRT task. Differences among
      individual study effect sizes, examined with meta-regression, indicated that
      smaller effect sizes were found in studies with older participants, and in
      studies that had a larger number of trials on the SRT task. The contributions of
      age and SRT task characteristics to learning are discussed with respect to
      impaired and compensatory neural mechanisms in SLI. 

PMID- 24315732
TI  - How do health care professionals assess patients when initiating insulin therapy?
      A qualitative study.
AB  - AIMS: To explore how health care professionals (HCPs) assess patients when
      initiating insulin therapy in type 2 diabetes. METHODS: Focus group discussions
      and in-depth interviews were conducted with 41 health care professionals in
      Malaysia in 2010-2011. A semi-structured topic guide was used for the interview.
      The interviews were transcribed verbatim and analysed using the Nvivo9 software
      based on a thematic approach. RESULTS: HCPs were less likely to initiate insulin
      therapy in patients who were older, with irregular dietary patterns and poor
      financial status. They also assessed patients' knowledge, views and
      misconceptions of insulin. However, there was a variation in how doctors assessed
      patients' comorbidities before starting insulin therapy. Medical officers were
      more likely to initiate insulin therapy in patients with comorbidities and
      complications, whereas family medicine specialists were more cautious. In
      addition, most HCPs considered patients' psychosocial status, including self-care
      ability, social support and quality of life. CONCLUSIONS: HCPs' assessment of
      patients' need to start insulin therapy depends on their perception rather than
      objective evaluation of patients' background, knowledge, perception and
      abilities. The background and the type of practice of HCPs influence their
      assessment.

PMID- 24315733
TI  - Reproducibility of vibration perception threshold values in children and
      adolescents with type 1 diabetes mellitus and associated factors.
AB  - AIMS: To define the reproducibility of vibration perception thresholds (VPTs) and
      the possible associated factors, as an early index of peripheral diabetic
      neuropathy (PDN) in type 1 diabetes mellitus (T1DM) children and adolescents.
      METHODS: A single examiner studied 118 T1DM subjects (aged 13.5+/-3.4 years) and
      79 controls (aged 12.0+/-3.07 years). Glycaemic control was assessed with HbA1c
      levels. VPT was measured twice on upper and lower limbs, using a Biothesiometer.
      Concordance between the two VPT measurements was evaluated using the Cohen's
      Weighted Kappa statistic (Kappa=0.41-0.60->moderate concordance, Kappa=0.61-0.80
      >substantial concordance). RESULTS: T1DM children had significantly higher VPTs
      than controls at all sites (p=0.001), but with lower Kappa values (0.64-0.70).
      VPT values increased in parallel with HbA1c (a.<8%, b. 8-9.5%, c.>9.5%) and T1DM
      duration (a.<5 years, b.5.1-10, c.>10 years). However, Kappa values were lower in
      the groups with the poorest control (HbA1c>9.5%) (Kappa=0.54-0.76) or the longest
      T1DM duration (>10 years) (Kappa=0.49-0.71). Although VPTs increased with stature
      and male gender, no effect on VPT reproducibility was observed. However, obesity
      was associated with lower VPT values and poorer concordance. CONCLUSIONS: These
      findings suggest that the reproducibility of VPTs is lower in the high-risk
      patients for early subclinical PDN development, who need a regular follow-up.

PMID- 24315734
TI  - Multifocal, recurrent sinonasal leiomyosarcoma: case report and review of
      literature.
AB  - Leiomyosarcoma is a rare tumor encountered in the sinus and skull base, and can
      be difficult to control. We present a case of an 83 year old female with a
      recurrent sinonasal leiomyosarcoma. The tumor exhibited variable growth rates of
      recurrences in non-contiguous sites despite having obtained clear surgical
      margins and use of adjuvant therapy. This case illustrates unusual
      characteristics of this rare tumor that are important for clinicians to know.
      Patient demographics, presenting symptoms, risk factors, treatment options, and
      prognosis are also reviewed.

PMID- 24315735
TI  - Blood otorrhea: blood stained sweaty ear discharges: hematohidrosis; four case
      series (2001-2013).
AB  - INTRODUCTION: Hematohidrosis/hematidrosis/hemidrosis is a rare clinical condition
      in which human being sweats blood under condition of extreme physical or
      emotional stress [1. Jerajai HR, Bhagyashri Jaju, Phiske MM, and Nitin Lade.
      Hematohidrosis-a rare clinical phenomenon. Indian J Dermatol. 2009 Jul-Sep;
      54(3): 290-292; 2. Martinez NL, Mas IB, Paz AFM, Boronat JL. Recurrent bleeding
      in an 18-year old girl. Arch Dermatol.2012; 148(8):960-961.] The capillary blood
      vessels that feed the sweat glands rupture, causing them to exude blood as sweat,
      under stressful conditions, occurring in religious (Jesus Christ prayer
      experience in Gethsemane) and non-religious (soldier sweat blood before battle)
      [2. Martinez NL, Mas IB, Paz AFM, Boronat JL. Recurrent bleeding in an 18-year
      old girl. Arch Dermatol.2012; 148(8):960-961.]. It is a condition where there is
      a spontaneous painless bleeding through unbroken skin in any part of the body. It
      is self-limiting in nature with a good prognosis [3. Patel RM, Mahajan S.
      Hematohidrosis: A rare clinical entity. Indian Dermatol Online J.2010 Jul;
      1(1):30-2.]. The diagnosis of hematohidrosis is made on the presence of bloody
      discharge without any obvious cause through intact skin, witnessed and confirmed
      by health professional/doctor/nurse and the presence of blood components on
      biochemistry studies of the discharge. Hematohidrosis is a well-recognised
      diagnosis according to International Classification of Diseases (ICD-9-CM: 705
      89) (ICD9 Data.com; 2013). CASE REPORT: This study reports the clinical finding,
      radiology, audiology and histology of four cases of a rare isolated otological
      hematohidrosis. Our cases are of particular interest because to our knowledge
      these are the first documented cases of psychogenic hematohidrosis isolated
      otological (ear) presentation. DISCUSSION: A comprehensive literature review was
      performed on reports documenting hematohidrosis/hematidrosis cases. The clinical
      presentation, diagnosis, treatment, pathophysiology and epidemiology of
      hematohidrosis. The purpose is to report and raise awareness of hematohidrosis
      among ENT patients.

PMID- 24315736
TI  - [A peripartum lumbosciatica revealing an Ewing sarcoma of the pelvis].

PMID- 24315738
TI  - Preoperative estimation of pedicled latissimus dorsi flap weight for breast
      reconstruction.

PMID- 24315737
TI  - RAD51C--a new human cancer susceptibility gene for sporadic squamous cell
      carcinoma of the head and neck (HNSCC).
AB  - INTRODUCTION: Head and neck squamous cell carcinomas (HNSSCs) are one of the
      leading causes of cancer-associated death worldwide. Although certain behavioral
      risk factors are well recognized as tumor promoting, there is very little known
      about the presence of predisposing germline mutations in HNSCC patients. METHODS:
      In this study, we analyzed 121 individuals with HNSCCs collected at our
      institution for germline alterations in the newly identified cancer
      susceptibility gene RAD51C. RESULTS: Sequencing of all exons and the adjacent
      introns revealed five distinct heterozygous sequence deviations in RAD51C in
      seven patients (5.8%). A female patient without any other risk factors carried a
      germline mutation that disrupted the canonical splice acceptor site of exon 5
      (c.706-2A>G). CONCLUSIONS: As there are only a few publications in the literature
      identifying germline mutations in head and neck cancer patients, our results
      provide the first indication that paralogs of RAD51, recently described as
      mutated in breast and ovarian cancer patients, might also be candidates for
      genetic risk factors in sporadic squamous cell carcinomas of the head and neck.

PMID- 24315739
TI  - Characterizing metal levels and their speciation in intertidal sediments along
      Mumbai coast, India.
AB  - The present study investigated the concentration, distribution and speciation of
      metals (Fe, Mn, Cu, Pb, Co, Zn and Cr) in sediments of Mumbai region. Pearson's
      correlation matrix and cluster analyses showed good association of metals with
      grain size and organic matter. Factor analysis applied to the speciation data
      helped to identify the role of different sediment fractions in metal retention.
      The environmental risks of metals, evaluated by sediment quality guidelines,
      revealed some contamination in the region. However, the Individual and Global
      Contamination Factors and the Risk Assessment Code, suggested low risk to the
      aquatic environment, except of Mn in the creek sediments. 

PMID- 24315740
TI  - 'Programs' aren't enough: child protection must become a part of everyday life.

PMID- 24315741
TI  - Role of the immune system in pancreatic cancer progression and immune modulating
      treatment strategies.
AB  - Traditional chemotherapeutics have largely failed to date to produce significant
      improvements in pancreatic cancer survival. One of the reasons for the resilience
      of pancreatic cancer towards intensive treatment is that the cancer is capable of
      high jacking the immune system: during disease progression the immune system is
      converted from a system that attacks tumor cells into a support structure for the
      cancer, exerting trophic actions on the cancer cells. This turn-around of immune
      system action is achieved through mobilization and activation of regulatory T
      cells, myeloid derived suppressor cells, tumor-associated macrophages and
      fibroblasts, all of which suppress CD8 T cells and NK cells. This immune
      suppression occurs both through the expression of tolerance-inducing cell surface
      molecules, such as PD-L1, as well as through the production of "tolerogenic"
      cytokines, such as IL-10 and TGF-beta. Based on the accumulating insight into the
      importance of the immune system for the outcome of pancreatic cancer patients
      multiple new immunotherapeutic approaches against pancreatic cancer are being
      currently tested in clinical trials. In this review we give an overview of both
      the immune escaping mechanisms of pancreatic cancer as well as the new immune
      related therapeutic strategies currently being tested in pancreatic cancer
      clinical trials. 

PMID- 24315742
TI  - [Reply].

PMID- 24315743
TI  - [Metabolic alkalosis with hyponatremia, hypokalemia and hypochloremia as the
      initial presentation of cystic fibrosis in an adult patient].

PMID- 24315744
TI  - [Plasmapheresis in the treatment of an acute pancreatitis due to
      hypertriglyceridemia].

PMID- 24315745
TI  - [Burning mouth syndrome: diagnostic and therapeutic keys].

PMID- 24315746
TI  - [Detection of left ventricular hypertrophy during the assessment of
      cardiovascular risk in hypertensive patients].

PMID- 24315747
TI  - [Syphilis and pregnancy: do we think of neurosyphilis?].

PMID- 24315748
TI  - [Fibromyalgia: comorbidity indicative of vulnerability?].

PMID- 24315749
TI  - [Immunological studies and specific bronchial challenge tests, essential
      techniques for the diagnosis of hypersensitivity pneumonitis].

PMID- 24315750
TI  - [The Fuller's earth and other digestive decontamination measures in the treatment
      of poisoning].

PMID- 24315751
TI  - Cancer stem cell enrichment marker CD98: a prognostic factor for survival in
      patients with human papillomavirus-positive oropharyngeal cancer.
AB  - PURPOSE: Several hypotheses have been proposed to explain the relatively good
      prognosis of patients with a human papillomavirus (HPV)-positive oropharyngeal
      squamous cell carcinoma (OPSCC) and one of these is a higher sensitivity to
      (chemo)radiation. Previous studies have suggested that treatment failure in OPSCC
      patients is caused by resistance of cancer stem cells (CSCs). The purpose of this
      study was to evaluate the association between the number of CSCs and prognosis in
      HPV-positive OPSCC patients. EXPERIMENTAL DESIGN: All OPSCC patients (n=711)
      treated between 2000 and 2006 in two Dutch university hospitals were included.
      Presence of HPV in a tumour tissue specimen was tested by p16-immunostaining
      followed by HPV DNA GP5+/6+polymerase chain reaction (PCR). The presence and
      intensity of tumour CSC markers CD44 and CD98 were determined by
      immunohistochemistry and semiquantitative scoring was performed. Overall survival
      (OS) and progression-free survival (PFS) rates were compared between patients
      with low and high CD44/CD98 expression in relation to HPV status. RESULTS: HPV
      positive tumours showed a lower percentage of cells with CD44 and CD98 expression
      than HPV-negative tumours (p<0.001, chi(2)-test). Within the group of patients
      with HPV-positive OPSCC, a high percentage of CD98-positive tumour cells was
      associated with a significantly worse 5-year OS and PFS (OS: 36.4% and PFS:
      27.3%) compared to patients with a low percentage of CD98-positive cells (OS:
      71.9% and PFS: 70.5%, respectively) (p<0.001). CONCLUSIONS: HPV-positive OPSCCs
      harbour fewer cells expressing the CSC enrichment markers CD44 and CD98.
      Furthermore, OS and PFS were significantly worse for patients with HPV-positive
      OPSCC with a high percentage of CD98-positive cells.

PMID- 24315752
TI  - Low-dose intrathecal fluorescein and etiology-based graft choice in endoscopic
      endonasal closure of CSF leaks.
AB  - OBJECTIVE: Skull base cerebrospinal fluid (CSF) leaks of various etiologies are
      increasingly repaired through the natural corridor using an endoscopic endonasal
      approach. Characteristics of the skull base defect significantly correlate with
      etiology, which should be ascertained to guide surgical management. The
      objectives of this study were to assess the long-term outcomes of patients that
      underwent endoscopic endonasal repair of CSF leak using low-dose intrathecal
      fluorescein (ITF) and an etiology-based algorithm for multi-layer graft closure.
      METHODS: Patients were divided into 4 groups: A--congenital, B--post-traumatic, C
      -post-endonasal surgery, D--post-craniotomy. Low-dose ITF was utilized in all
      case series. Long-term clinical follow-up data, including perioperative
      complications associated with the use of intrathecal fluorescein and leak closure
      rates, were obtained retrospectively. Endoscopic visualization of fluorescein
      stained CSF as well as the method of skull base closure and graft material is
      detailed. RESULTS: We identified a total of 41 patients (N=24 in Group A, N=4 in
      Group B, N=12 in Group C and N=1 in Group D) that underwent 50 CSF leak repairs
      using the endoscopic endonasal approach with an average follow-up of 31.6 months.
      Nine patients (21.9%) had undergone a previous attempt at CSF leak repair. Lumbar
      drain was used intraoperatively in 26 patients (63.4%) and kept in place for an
      average duration of 3.25 days. ITF successfully identified the site of leak in
      80.5% of cases regardless of etiology. Leaks were successfully closed in 92% of
      patients. One patient (2.4%) experienced transient leg weakness following lumbar
      drain placement. Another patient (2.4%) developed hydrocephalus requiring a
      ventriculoperitoneal shunt. CONCLUSION: Low-dose ITF is a safe and useful adjunct
      to endoscopic endonasal repair of CSF leaks with minimal complications and
      successful localization of the leak in approximately 80%. An etiology-based
      approach to graft choice and duration of lumbar drain placement in CSF leak
      repair may optimize closure rates.

PMID- 24315753
TI  - Identification and characterization of the free fatty acid receptor 2 (FFA2) and
      a novel functional FFA2-like receptor (FFA2L) for short-chain fatty acids in
      pigs: evidence for the existence of a duplicated FFA2 gene (FFA2L) in some
      mammalian species.
AB  - Free fatty acid receptor 2 (FFA2, also called GPR43) is reported to play a
      critical role in mediating the actions of short-chain fatty acids (SCFAs) in
      humans and mice. However, little is known about the structure, functionality, and
      tissue expression of FFA2 in other mammalian species, including pigs. In the
      present study, the full-length cDNAs of FFA2 (pFFA2) and a novel FFA2-like gene
      (named pFFA2L) were cloned from pig intestines by reverse transcription PCR. Both
      cloned pFFA2 and pFFA2L are predicted to encode 2 receptors of remarkable
      structural similarity and share high amino acid sequence identities with FFA2
      from other mammalian species. Interestingly, the novel FFA2L could also be
      identified in 9 other mammalian species, suggesting that FFA2L was likely
      duplicated from FFA2 in the last common ancestor of these species. With the use
      of a pGL4-SRE-luciferase reporter assay, we demonstrated that pFFA2 expressed in
      human embryonic kidney 293 cells could be activated by acetate, propionate, and
      butyrate equipotently, whereas pFFA2L could be activated only by acetate and
      propionate, indicating that both pFFA2 and pFFA2L are functional receptors for
      SCFAs with nonidentical pharmacologic properties. Reverse transcription PCR found
      that pFFA2 mRNA was widely expressed in nearly all tissues examined, including
      adipose tissue and gastrointestinal (GI) tract, whereas pFFA2L expression was
      mainly restricted to the GI tract. Taken together, our findings raise a novel
      concept that the actions of SCFAs are likely mediated by 2 FFA2s (FFA2 and FFA2L)
      in target tissues of some mammalian species, such as the GI tract of pigs. 

PMID- 24315754
TI  - Effects of the rate of insulin infusion during isoglycemic, hyperinsulinemic
      clamp procedures on measures of insulin action in healthy, mature thoroughbred
      mares.
AB  - The objective of this study was to determine whether the rate of insulin infusion
      during isoglycemic hyperinsulinemic clamp procedures affected measures of insulin
      action, including glucose disposal and plasma non-esterified fatty acid,
      endothelin-1, and nitric oxide concentrations, in mature, healthy horses. Eight
      thoroughbred mares were studied during a 2-h hyperinsulinemic clamp procedure,
      conducted at each of 4 rates of insulin infusion: 0 (CON), 1.2 (LOWINS), 3
      (MEDINS), and 6 (HIGHINS) mU . kg(-1) . min(-1). The infusion rate of a dextrose
      solution was adjusted throughout the clamp procedures to maintain blood glucose
      levels within 10% of baseline glucose concentrations. Plasma insulin
      concentrations were measured throughout the clamp procedures, and used with the
      rate of glucose infusion to calculate the plasma insulin concentration-to-rate of
      glucose infusion ratio, a measure of insulin action on glucose disposal. The rate
      of glucose infusion increased with rate of insulin infusion (P < 0.05). The
      plasma insulin concentration-to-rate of glucose infusion ratio was highest for
      the LOWINS treatment (P < 0.05) and decreased by 62% (P < 0.05) and 84% (P <
      0.05) for the MEDINS and HIGHINS treatments, respectively. Although plasma non
      esterified fatty acid concentrations were lower than baseline by t = 30 min of
      the clamp procedures in the LOWINS, MEDINS, and HIGHINS treatments (P < 0.05),
      the decline was similar for all 3 rates of insulin infusion. Jugular vein plasma
      nitric oxide and endothelin-1 concentrations were not affected by insulin
      infusion rate (P > 0.05). The data indicate that it is important to standardize
      insulin infusion rate if data are to be compared between hyperinsulinemic clamp
      studies.

PMID- 24315755
TI  - Insulin infusion stimulates whole-body protein synthesis and activates the
      upstream and downstream effectors of mechanistic target of rapamycin signaling in
      the gluteus medius muscle of mature horses.
AB  - Little is known about the role insulin plays in regulating whole-body and muscle
      protein metabolism in horses. The objective of this study was to determine the
      effects of graded rates of insulin infusion on plasma amino acid concentrations
      and the activation of factors in the mechanistic target of rapamycin signaling
      pathway in the skeletal muscle of horses. Isoglycemic, hyperinsulinemic clamp
      procedures were conducted in 8 mature, thoroughbred mares receiving 4 rates of
      insulin infusion: 0 mU . kg(-1) . min(-1) (CON), 1.2 mU . kg(-1) . min(-1)
      (LOWINS), 3 mU . kg(-1) . min(-1) (MEDINS), and 6 mU . kg(-1) . min(-1)
      (HIGHINS). Blood samples were taken throughout the clamp procedures to measure
      plasma amino acid concentrations, and a biopsy from the gluteus medius muscle was
      collected at the end of the 2-h clamp to measure phosphorylation of protein
      kinase B, eukaryotic initiation factor 4E-binding protein 1, and riboprotein S6.
      Plasma concentrations of most of the essential amino acids decreased (P < 0.05)
      after 120 min of insulin infusion in horses receiving the LOWINS, MEDINS, and
      HIGHINS treatments, with the largest decreases occurring in horses receiving the
      MEDINS and HIGHINS treatments. Phosphorylation of protein kinase B, 4E-binding
      protein 1, and riboprotein S6 increased with all 3 rates of insulin infusion (P >
      0.05), relative to CON, with maximum phosphorylation achieved with MEDINS and
      HIGHINS treatments. These results indicate that insulin stimulates whole-body and
      muscle protein synthesis in mature horses.

PMID- 24315756
TI  - Acute kidney injury assessed by cystatin C after transcatheter aortic valve
      implantation and late renal dysfunction.
AB  - OBJECTIVE: The aim of the present study was to evaluate acute kidney injury (AKI)
      with cystatin C following transcatheter aortic valve implantation (TAVI) and to
      assess the impact of postoperative AKI on outcome and late renal function.
      DESIGN: A prospective study. SETTING: Single, tertiary referral center.
      PARTICIPANTS: Sixty-eight consecutive patients with severe aortic stenosis and
      advanced comorbidity. INTERVENTIONS: Blood samples were collected on 4 occasions
      pre- and postoperatively to determine levels of s-creatinine and cystatin C.
      Additionally, a sample was collected at followup 12 months postoperatively for
      the determination of s-creatinine. MEASUREMENTS AND MAIN RESULTS: The mean
      preoperative eGFR (s-creatinine) was 67+/-24 mL/min/1.73 m2 compared to 45+/-21
      mL/min/1.73 m2 with eGFR (cystatin C) (p<0.001). Postoperative AKI was diagnosed
      in 25 patients (39%) with eGFR (cystatin C), compared to 21 patients (33%) with
      GFR (s-creatinine) and the RIFLE criteria. The 90-day mortality was 14.3% for the
      AKI+group and 2.3% for the AKI-group (p = 0.099). At 12 months followup, renal
      function remained impaired in patients with postoperative AKI and deteriorated in
      patients without. CONCLUSIONS: The risk of postoperative AKI is considerable
      following TAVI, with an increased risk of early mortality for AKI+patients.
      Cystatin C may be a valuable adjunct to the established biomarker s-creatinine
      for preoperative risk assessment and for early postoperative diagnosis of AKI.
      The acute postoperative renal impairment in patients with AKI does not fully
      recover in the long term. There is a progressive renal impairment in both groups
      postoperatively, the etiology probably being multifactorial.

PMID- 24315757
TI  - Anesthetic management of patients undergoing transcatheter aortic valve
      implantation.
AB  - OBJECTIVE: To compare 2 anesthetic techniques, general anesthesia or monitored
      anesthesia care, performed by the same cardiac anesthesiologists for
      transcatheter aortic valve implantation in the authors' institution. DESIGN: A
      retrospective study. SETTING: A single specialized cardiac surgery center.
      PARTICIPANTS: Ninety-eight patients with severe aortic valve stenosis and a high
      logistic EuroSCORE considered not eligible to undergo conventional aortic valve
      replacement. INTERVENTION: General anesthesia or monitored anesthesia care.
      MEASUREMENTS AND MAIN RESULTS: General anesthesia was used in 57 and monitored
      anesthesia care in 41 patients. The authors compared the following parameters:
      Duration of procedure, transfusion requirements, cardiac indices, superior vena
      cava saturation (ScVO2) before and after the aortic valve implantation, hospital
      length of stay and 30-day mortality. The only significant differences between the
      groups concerned were the duration of anesthesia (p<0.001) and ScVO2 values.
      Anesthesia duration was prolonged significantly when general anesthesia was
      administered, and ScVO2 was significantly higher both before and after the valve
      implantation in the general anesthesia group. Thirty-day mortality was 5.3% in
      the general anesthesia group and 4.9% in the monitored anesthesia group.
      CONCLUSIONS: It would appear that both anesthetic techniques may be used for
      patients with a high logistic EuroSCORE undergoing transcatheter aortic valve
      implantation.

PMID- 24315758
TI  - Major positional obstruction of the trachea in a patient with a right-sided
      aortic arch and Kommerell's diverticulum.

PMID- 24315759
TI  - Benefits and risks of epidural analgesia in cardiac surgery.

PMID- 24315760
TI  - Vertical distribution of lipids, fatty acids and organochlorine contaminants in
      the blubber of southern hemisphere humpback whales (Megaptera novaeangliae).
AB  - Persistent organic pollutants (POPs), such as toxic lipophilic organochlorine
      (OC) compounds, accumulate in the blubber tissue of marine mammals. Toxicological
      sampling methods most frequently target only the superficial blubber layer.
      Vertical distribution of these contaminants through the blubber mantle may,
      however, not be homogenous and could reflect any dissemination of lipids and
      fatty acids (FAs). It is therefore critical to assess stratification patterns in
      a species of interest as a quality control measure for interpretation of
      toxicological data. Here, we analysed and compared the distribution of lipids,
      FAs, and OCs in the outermost and innermost blubber layer of southern hemisphere
      humpback whales. FA stratification was evident for short-chain (<=18)
      monounsaturated fatty acids (SC-MUFA), which were concentrated in the outer
      layer, consistent with the thermoregulatory role of this blubber layer. This
      stratification was, however, not reflected in OC distribution, which was similar
      in the inner and outer blubber layers of male humpback whales. By comparison, a
      noticeable gradient in total blubber lipid from the outer to the inner layer was
      observed in two lactating females, which coincided with higher lipid normalised
      contaminant levels in the inner layer. This study contains the most comprehensive
      assessment of humpback whale blubber stratification to date, however, further
      investigation of biological and ecological influencing factors is required. 

PMID- 24315761
TI  - Psoriasis-like skin lesions are dependent on IL-23 but develop in the absence of
      IL-22 in a model mouse.

PMID- 24315762
TI  - Differential expression of BAFF and its receptors in discoid lupus erythematosus
      patients.
AB  - BACKGROUND: B-cell activating factor of the TNF family (BAFF) promotes the
      maturation and survival of B cells. Because BAFF levels are elevated in systemic
      lupus erythematosus (SLE) patients, BAFF has been the target of emerging
      therapies for SLE, such as belimumab. Levels of BAFF and its receptors in discoid
      lupus erythematosus (DLE) patients are unknown. OBJECTIVE: To compare skin and
      blood mRNA and protein levels of BAFF and its receptors BAFF-R, TACI, and BCMA in
      DLE subjects with (DLE+/SLE+ (N=28)) and without SLE (DLE+/SLE- (N=35)),
      psoriasis subjects (N=11), and normal subjects (N=42). METHODS: We used
      quantitative real-time PCR to measure blood and skin BAFF, BAFF-R, TACI, and BCMA
      mRNA, sandwich ELISAs to measure sera BAFF, and immunohistochemistry to evaluate
      BAFF and BAFF-R skin protein expression. RESULTS: BAFF mRNA and protein levels
      were highest in DLE+/SLE+blood, followed by DLE+/SLE-, psoriasis, and normal
      blood. BAFF protein also correlated with anti-nuclear antibodies, and
      autoantibodies against double-stranded DNA, single-stranded DNA, and
      ribonucleoprotein, and Systemic Lupus Erythematosus Disease Activity Index scores
      in DLE patients. While showing no difference between DLE+/SLE+ and DLE+/SLE-
      skin, BAFF and its receptors mRNA were up-regulated in DLE skin vs. normal and
      psoriasis skin. DLE skin had higher percentages of BAFF-R+ inflammatory cells,
      likely T cells and macrophages, than psoriasis and normal skin. CONCLUSIONS: BAFF
      may be a serologic marker of systemic disease in DLE patients. BAFF and its
      receptors are elevated in DLE skin, suggesting that targeted therapies against
      these proteins could treat refractory DLE patients.

PMID- 24315763
TI  - Involvement of HLA class I molecules in the immune escape of urologic tumors.
AB  - CONTEXT AND OBJECTIVE: To analyze the influence of different alterations in human
      leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as
      in bladder and prostate cancer. We also study the correlation between HLA I
      expression and the progression of the disease and the response after
      immunotherapy protocols. EVIDENCES ACQUISITION: It has been shown,
      experimentally, that the immune system can recognize and kill neoplastic cells.
      By analyzing the expression of HLA I molecules on the surface of cancer cells, we
      were able to study the tumor escape mechanisms against the immune system.
      EVIDENCES SYNTHESIS: Alteration or irreversible damage in HLA I molecules is used
      by the neoplastic cells to escape the immune system. The function of these
      molecules is to recognize endogenous peptides and present them to T cells of the
      immune system. There is a clear relationship between HLA I reversible alterations
      and success of therapy. Irreversible lesions also imply a lack of response to
      treatment. The immune system activation can reverse HLA I molecules expression in
      tumors with reversible lesions, whereas tumors with irreversible ones do not
      respond to such activation. Determine the type of altered HLA I molecules in
      tumors is of paramount importance when choosing the type of treatment to keep
      looking for therapeutic success. Those tumors with reversible lesions can be
      treated with traditional immunotherapy; however, tumour with irreversible
      alterations should follow alternative protocols, such as the use of viral vectors
      carrying the HLA genes to achieve damaged re-expression of the protein.
      CONCLUSION: From studies in urologic tumors, we can conclude that the HLA I
      molecules play a key role in these tumors escape to the immune system.

PMID- 24315765
TI  - Early ultrafiltration failure in a patient with familial focal segmental
      glomerulosclerosis secondary to a mutation in alpha-actinin-4: a postulated
      extrarenal manifestation of hereditary focal sclerosis.

PMID- 24315764
TI  - Echocardiographic evaluation of the effects of stem cell therapy on perfusion and
      function in ischemic cardiomyopathy.
AB  - BACKGROUND: Small animal models of ischemic left ventricular (LV) dysfunction are
      important for the preclinical optimization of stem cell therapy. The aim of this
      study was to test the hypothesis that temporal changes in LV function and
      regional perfusion after cell therapy can be assessed in mice using
      echocardiographic imaging. METHODS: Wild-type mice (n = 25) were studied 7 and 28
      days after permanent ligation of the left anterior descending coronary artery.
      Animals were randomized to receive closed-chest ultrasound-guided intramyocardial
      delivery of saline (n = 13) or 5 * 10(5) multipotential adult progenitor cells
      (MAPCs; n = 12) on day 7. LV end-diastolic and end-systolic volumes, LV ejection
      fraction, and stroke volume were measured using high-frequency echocardiography.
      Multiplanar assessments of perfusion and defect area size were made using
      myocardial contrast echocardiography. RESULTS: Between days 7 and 28, MAPC
      treated animals had 40% to 50% reductions in defect size (P < .001) and 20% to
      30% increases in total perfusion (P < .01). Perfusion did not change in
      nontreated controls. Both LV end-diastolic and end-systolic volumes increased
      between days 7 and 28 in both groups, but LV end-systolic volume increased to a
      lesser degree in MAPC-treated compared with control mice (+4.2 +/- 7.9 vs +19.2
      +/- 22.0 MUL, P < .05). LV ejection fraction increased in the MAPC-treated mice
      and decreased in control mice (+3.0 +/- 4.3% vs -5.6 +/- 5.9%, P < .01). There
      was a significant linear relation between the change in LV ejection fraction and
      the change in either defect area size or total perfusion. CONCLUSIONS: High
      frequency echocardiography and myocardial contrast echocardiography in murine
      models of ischemic LV dysfunction can be used to assess the response to stem cell
      therapy and to characterize the relationship among spatial flow, ventricular
      function, and ventricular remodeling.

PMID- 24315766
TI  - Acute interstitial nephritis after treatment with liraglutide.

PMID- 24315767
TI  - Idiopathic granulomatous interstitial nephritis responsive to mycophenolate
      mofetil therapy.
AB  - Granulomatous interstitial nephritis (GIN) is a rare histologic disease. Various
      causes have been reported in the literature, including drugs, sarcoidosis, and
      infections. Other incidents have no discernible cause and are identified as
      idiopathic. We report a 68-year-old white man who presented with acute kidney
      injury and was given a diagnosis of idiopathic GIN. Mycophenolate mofetil
      treatment was elected because of steroid toxicity. He responded well to
      mycophenolate mofetil and has been in remission for more than 3 years. To our
      knowledge, this is the first report of successful treatment with mycophenolate
      mofetil of an adult patient with idiopathic GIN. 

PMID- 24315768
TI  - Thyroid function, cardiovascular events, and mortality in diabetic hemodialysis
      patients.
AB  - BACKGROUND: In dialysis patients, the prevalence of thyroid disorders and their
      impact on specific cardiovascular (CV) events and mortality are largely unknown.
      The aim of the present study was to analyze whether subclinical thyroid disorders
      were associated with CV events and mortality. STUDY DESIGN: Prospective
      multicenter cohort study. SETTING & PARTICIPANTS: Thyroid status and clinical
      outcomes were explored in 1,000 diabetic hemodialysis patients from 178 centers
      in Germany. PREDICTOR: Thyroid status, defined by the following cutoff values:
      euthyroidism (thyrotropin [TSH], 0.30-4.0 mIU/L; free triiodothyronine [T3], 2.7
      7.6 pmol/L; and free thyroxine [T4], 11.0-24.0 pmol/L), subclinical
      hyperthyroidism (TSH<0.3 mIU/L and free T3/free T4 within reference ranges),
      subclinical hypothyroidism (TSH, 4.1-15.0 mIU/L and free T3/free T4 within
      reference ranges), euthyroid sick syndrome (free T3<2.7 pmol/L and TSH/free T4
      low or within reference ranges). OUTCOMES: During 4 years' follow-up,
      prespecified adjudicated end points were determined: sudden cardiac death,
      myocardial infarction, stroke, combined CV events, and overall mortality. Short
      term effects within the first 12 months were contrasted to long-term effects
      (years 2-4). MEASUREMENTS: TSH, free T3, and free T4 levels at baseline. RESULTS:
      Euthyroidism was present in 78.1% of patients; subclinical hyperthyroidism, in
      13.7%; and subclinical hypothyroidism, in 1.6%. Euthyroid sick syndrome was
      exhibited by 5.4% of patients. The adjusted short-term risk of sudden cardiac
      death was more than doubled (HR, 2.03; 95% CI, 0.94-4.36) in patients with
      subclinical hyperthyroidism, and similarly for patients with euthyroid sick
      syndrome (HR, 2.74; 95% CI, 0.94-7.98) compared with patients with euthyroidism.
      Short-term mortality was increased almost 3-fold for patients with euthyroid sick
      syndrome (HR, 2.97; 95% CI, 1.66-5.29), but this effect was not seen in the long
      term. Subclinical hypothyroidism was not associated with CV events or all-cause
      mortality. Risks of stroke and myocardial infarction were not affected
      meaningfully by thyroid disorders. LIMITATIONS: Observational study design.
      CONCLUSIONS: Sudden cardiac death may be influenced by subclinical
      hyperthyroidism and euthyroid sick syndrome in the short term. Furthermore,
      euthyroid sick syndrome is associated strongly with mortality in hemodialysis
      patients. Regular assessment of thyroid status may help estimate the cardiac risk
      of dialysis patients.

PMID- 24315769
TI  - Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional
      study.
AB  - BACKGROUND: Serum total and low-density lipoprotein (LDL) cholesterol levels are
      elevated in patients with nephrotic syndrome and those with kidney failure
      treated by peritoneal dialysis (PD), who are characterized by heavy losses of
      protein in urine and peritoneal dialysate, respectively. Hypercholesterolemia in
      nephrotic syndrome is associated with and largely due to acquired LDL receptor
      (LDLR) deficiency. Because PCSK9 (proprotein convertase subtilisin/kexin type 9)
      promotes degradation of LDLR, we tested the hypothesis that elevation of LDL
      cholesterol levels in patients with nephrotic syndrome and PD patients may be due
      to increased PCSK9 levels. STUDY DESIGN: Cross-sectional study. SETTING &
      PARTICIPANTS: Patients with nephrotic syndrome or treated by PD or hemodialysis
      and age- and sex-matched healthy Korean individuals (n=15 in each group).
      PREDICTOR: Group and serum total and LDL cholesterol levels. OUTCOMES: Plasma
      PCSK9 concentration. MEASUREMENTS: Concentrations of fasting serum PCSK9, lipids,
      and albumin, and urine protein excretion. RESULTS: Mean serum total and LDL
      cholesterol levels in patients with nephrotic syndrome (317.9+/-104.2 [SD] and
      205.9+/-91.1mg/dL) and PD patients (200.0+/-27.6 and 126.7+/-18.5mg/dL) were
      significantly (P<0.05) higher than in hemodialysis patients (140.9+/-22.9 and
      79.1+/-19.5mg/dL) and the control group (166.5+/-26.5 and 95.9+/-25.2mg/dL). This
      was associated with significantly (P<0.05) higher plasma PCSK9 levels in patients
      with nephrotic syndrome (15.13+/-4.99ng/mL) and PD patients (13.30+/-1.40ng/mL)
      than in the control (9.19+/-0.60ng/mL) and hemodialysis (7.30+/-0.50ng/mL)
      groups. Plasma PCSK9 level was directly related to total and LDL cholesterol
      concentrations in the study population (r=0.559 [P<0.001] and r=0.497 [P<0.001],
      respectively). LIMITATIONS: Small number of participants may limit
      generalizability. CONCLUSIONS: Nephrotic syndrome and PD are associated with
      higher plasma PCSK9 concentration, which can contribute to elevation of LDL
      levels by promoting LDLR deficiency.

PMID- 24315771
TI  - Genetics and urinary tract malformations.

PMID- 24315770
TI  - Effect of facility-level hemoglobin concentration on dialysis patient risk of
      transfusion.
AB  - BACKGROUND: Changes in anemia management practices due to concerns about
      erythropoiesis-stimulating agent safety and Medicare payment changes may increase
      patient risk of transfusion. We examined anemia management trends in hemodialysis
      patients and risk of red blood cell (RBC) transfusion according to dialysis
      facility-level hemoglobin concentration. STUDY DESIGN: Retrospective follow-up
      study; 6-month study period (January to June), 3-month exposure/follow-up.
      SETTING & PARTICIPANTS: For each year in 2007-2011, annual cohorts of point
      prevalent Medicare primary payer patients receiving hemodialysis on January 1
      with one or more hemoglobin measurements during the study period. Annual cohorts
      averaged 170,000 patients, with 130,000 patients and 3,100 facilities for the
      risk analysis. PREDICTOR: Percentage of facility patient-months with hemoglobin
      level<10 g/dL. OUTCOME: Patient-level RBC transfusion rates. MEASUREMENTS:
      Monthly epoetin alfa and intravenous iron doses, mean hemoglobin levels, and RBC
      transfusion rates; percentage of facility patient-months with hemoglobin
      levels<10 g/dL (exposure) and patient-level RBC transfusion rates (follow-up).
      RESULTS: Percentages of patients with hemoglobin levels<10 g/dL increased every
      year from 2007 (6%) to 2011 (~11%). Epoetin alfa doses, iron doses, and
      transfusion rates remained relatively stable through 2010 and changed in 2011.
      Median monthly epoetin alfa and iron doses decreased 25% and 43.8%, respectively,
      and monthly transfusion rates increased from 2.8% to 3.2% in 2011, a 14.3%
      increase. Patients in facilities with the highest prevalence of hemoglobin
      levels<10 g/dL over 3 months were at ~30% elevated risk of receiving RBC
      transfusions within the next 3 months (relative risk, 1.28; 95% CI, 1.22-1.34).
      LIMITATIONS: Possibly incomplete claims data; smaller units excluded; hemoglobin
      levels reported monthly for patients receiving epoetin alfa; transfusions usually
      not administered in dialysis units. CONCLUSIONS: Dialysis facility treatment
      practices, as assessed by percentage of patient-months with hemoglobin levels<10
      g/dL over 3 months, were associated significantly with risk of transfusions in
      the next 3 months for all patients in the facility, regardless of patient case
      mix.

PMID- 24315772
TI  - Environmental philosophy 2.0: ethics and conservation biology for the 21st
      century.
AB  - In this essay, I critically engage Sahotra Sarkar's Environmental Philosophy. The
      several topics include the conceptual foundations of conservation biology and
      traditional philosophy of science, naturalism and its implications, and ethical
      theory and specifically the status of human welfare. 

PMID- 24315773
TI  - Community level physiological profiles of bacterial communities inhabiting
      uranium mining impacted sites.
AB  - Bacterial activity and physiological diversity were characterized in mining and
      milling impacted soils collected from three abandoned uranium mine sites,
      Senokos, Buhovo and Sliven, using bacterial dehydrogenase activity and Biolog
      (EcoPlate) tests. The elemental composition of soils revealed high levels of
      uranium and heavy metals (sum of technogenic coefficients of contamination;
      TCC(sum) pollution as follows: Sliven (uranium - 374 mg/kg; TCC(sum) - 23.40)
      >Buhovo (uranium - 139.20mg/kg; TCC(sum) - 3.93) >Senokos (uranium - 23.01 mg/kg;
      TCC(sum) - 0.86). The physiological profiles of the bacterial community level
      were site specific, and indicated intensive utilization of polyols, carbohydrates
      and carboxylic acids in low and medium polluted environments, and i-erithrytol
      and 2-hydroxy-benzoic acid in the highly polluted environment of Sliven waste
      pile. Enzymes which take part in the biodegradation of recalcitrant substances
      were more resistant to pollution than these from the pathways of the easily
      degradable carbon sources. The Shannon index indicated that the physiological
      diversity of bacteria was site specific but not in line with the levels of
      pollution. A general tendency of increasing the importance of the number of
      utilizable substrates to bacterial physiological diversity was observed at less
      polluted sites, whereas in highly polluted sites the evenness of substrate
      utilization rate was more significant. Dehydrogenase activity was highest in
      Senokos upper soil layer and positively correlated (p<0.01) with the soil organic
      matter content. The bacterial activity (EcoPlate) and physiological diversity
      (Shannon index) correlated significantly and negatively with As, Cu, Zn, Pb and
      U, and Co, Cr, Ni and Mn, respectively. We concluded that the observed site
      specific shifts in bacterial communities were complex due to both the
      environmental peculiarities and the bacterial tolerance to the relevant level of
      pollution, rather than a strong indication of uranium and heavy metals toxicity.

PMID- 24315774
TI  - [Control of blood pressure in hypertensive patients on combination therapy].
AB  - BACKGROUND AND AIM: The impact of antihypertensive treatment on blood pressure
      (BP) control is fairly unknown. The aim of the study was to evaluate the degree
      of BP control and its relationship with treatment-related factors in hypertensive
      patients treated with 2 or 3 agents and attended in referral units. PATIENTS AND
      METHODS: We studied 1,337 hypertensive subjects (41% women) with a mean age (SD)
      of 63 (12) years, who were receiving 2 or 3 antihypertensive drugs. The degree of
      BP control was estimated in a single visit by the proportion of patients with BP
      below 140/90mmHg. RESULTS: BP was controlled in 767 patients (57%). Lack of BP
      control was related to older age (12% risk for each 10-year increase) and the
      presence of microalbuminuria (64% risk increase). In those treated with 2 agents,
      BP control was 61%, without differences between those treated with fixed-drug or
      free combinations. BP control in those treated with 3 agents was 55%, higher in
      those receiving 3 agents in a fixed-drug combination (68%) compared with those on
      3 agents administered separately (52%; P=.025). Drug classes used in combinations
      did not influence the degree of BP control. CONCLUSIONS: The degree of BP control
      in patients treated with 2 or 3 agents is 57%. Microalbuminuria is related to a
      lack of BP control. In those receiving 3 agents, the use of fixed-drug
      combinations is associated with better BP control.

PMID- 24315775
TI  - HAHA antibodies -- not such a funny story.

PMID- 24315776
TI  - Increased Gardnerella vaginalis urogenital biofilm in inflammatory bowel disease.
AB  - INTRODUCTION: Inflammatory bowel disease (IBD) is a systemic inflammatory
      condition that affects the entire organism, not only the bowel. An impaired
      interaction with microbiota has been shown to be important. We looked for
      bacterial factors, which may contribute to the well-known higher incidence of
      poor reproductive outcome in IBD. METHODS: Urine specimen of patients with
      Crohn's disease (N=42), ulcerative colitis (N=46), and randomly selected patients
      attending the General Internal Medicine Outpatient Clinic of the Charite for non
      IBD related medical conditions (N=49) was analyzed for bacteria adherent to
      desquamated epithelial cells and diffusely distributed bacteria in the urine
      using fluorescence in situ hybridization. RESULTS: The urine of IBD patients
      contained significantly more often Gardnerella vaginalis biofilms (CD 38%, UC
      43%) than those of the control group (16%). There was no link between current
      disease activity, history of and present fistula and G. vaginalis biofilms, but
      the samples of patients with steroid refractory/dependent disease were
      significantly more often G. vaginalis biofilm positive. No significant
      differences in number of epithelial cells and leukocytes, and total bacterial
      counts were present. CONCLUSIONS: There is a significant link between IBD and G.
      vaginalis biofilm. This observation suggests an epithelial barrier dysfunction of
      the genital tract. Since G. vaginalis is believed to be one of the reasons
      responsible for bacterial vaginosis, it may be an important factor in the well
      known higher incidence of poor reproductive outcome in IBD. Excessive G.
      vaginalis biofilms in steroid refractory/dependent disease suggests a need to
      avoid long-term steroid therapy.

PMID- 24315777
TI  - Ileorectal anastomosis in comparison with ileal pouch anal anastomosis in
      reconstructive surgery for ulcerative colitis--a single institution experience.
AB  - INTRODUCTION: Ileal pouch anal anastomosis (IPAA) is the standard procedure for
      reconstruction after colectomy for ulcerative colitis (UC). However, ileorectal
      anastomosis (IRA) as an alternative has, recently experienced a revival. This
      study from a single center compares the clinical outcomes of these procedures.
      METHODS: From 1992 to 2006, 253 patients consecutively underwent either IRA
      (n=105) or IPAA (n=148). Selection to either procedure was determined on the
      basis of rectal inflammation, presence of dysplasia/cancer or patient
      preferences. Patient-records were retrospectively evaluated. Mean follow-up time
      was 5.4 and 6.3 years respectively. RESULTS: Major postoperative complications
      occurred in 12.4% of patients after IRA and in 12.8% after IPAA (ns).
      Complications of any kind after IRA or IPAA, even including subsequent stoma
      closure, occurred in 23.8% and 39.9% respectively (p<0.01). Estimated cumulative
      failure rates after 5 and 10 years were 10.1% and 24.1% for IRA and 6.1% and
      18.6% for IPAA respectively (ns). The most common cause for failure was
      intractable proctitis (4.8%) and unspecified dysfunction (4.8%) respectively. At
      follow-up 76.9% of patients with IRA had proctitis and 34.1% with IPAA had
      pouchitis. Estimated cumulative cancer-risk after 10, 20 and 25 year duration of
      disease was 0.0%, 2.1% and 8.7% for IRA. Figures for IPAA were 0.7%, 1.8% and
      1.8% (ns). CONCLUSION: Failure-rates did not significantly differ between
      patients operated with IRA or IPAA. Patients operated with IPAA had a higher
      cumulative number of postoperative complications. The high long-term cancer-risk
      after IRA indicates that this procedure should be an interim solution in younger
      patients.

PMID- 24315779
TI  - HPLC determination of D-3-hydroxybutyric acid by derivatization with a
      benzofurazan reagent and fluorescent detection: application in the analysis of
      human plasma.
AB  - A simple and sensitive new method for the determination of D-3-hydroxybutyric
      acid (D-3-HBA) in human plasma after derivatization is described. The proposed
      method is based on the reaction of (2S)-2-amino-3-methyl-1-[4-(7-nitro-benzo
      2,1,3-oxadiazol-4-yl)-piperazin-1-yl]-butan-1-one (NBD-PZ-Val) with D-3-HBA in
      the presence of O-(7-azobenzotriazol-1-yl)-1,1,3,3-tetramethyluronium
      hexafluorophosphate (HATU) and N-ethyldiisopropylamine (DIEA) to produce a
      fluorescent derivative. The formed derivative was monitored fluorimetrically at
      lambda(ex)=489 nm and lambda(em)=532 nm. The HPLC analysis was carried out by use
      of a C18 analytical column (Synergy Hydro 150 mm * 3 mm, i.d., 4 MUm) with a
      binary gradient elution program of 0.1% aqueous trifluoroacetic acid versus
      methanol. The method showed satisfactory linearity (r(2)=0.9997) in the range
      from 20 to 500 MUmol/L. The limit of detection (LOD) of the method was 7.7
      MUmol/L, while the limit of quantitation (LOQ) was 25.8 MUmol/L. The analytical
      method was successfully applied to human plasma samples from normal healthy
      subjects.

PMID- 24315778
TI  - Diet quality is associated with circulating C-reactive protein but not irisin
      levels in humans.
AB  - OBJECTIVE: Adherence to a healthy diet has been shown to decrease the incidence
      of obesity and associated comorbidities. C-reactive protein (CRP) is an
      established inflammatory marker and irisin was recently identified as a molecule
      which may play a role in energy regulation and obesity but whether diet alters
      irisin levels remains unknown. We aimed to investigate the association between
      circulating irisin, leptin, and CRP levels and dietary quantity and quality using
      the Alternate Healthy Eating Index (AHEI) and the Alternate Mediterranean Diet
      Score (aMED). MATERIALS/METHODS: The study evaluated dietary data and biomarker
      levels of 151 participants between 2009 and 2011 (71 male vs. 80 female, over 35
      years old, obese 43.7%). AHEI and aMED scores were calculated based on data
      derived from self-administered 110-item food-frequency questionnaires estimating
      usual nutrient intake over the past year. Cross-sectional associations between
      dietary quantity, quality, body composition by bioelectric impedance, and
      biomarker levels including irisin, leptin, and CRP after fasting were assessed.
      RESULTS: CRP, but not irisin, was negatively correlated with AHEI (r=-0.34) and
      aMED (r=-0.31). Irisin was positively correlated with BMI (r=0.22), fat mass
      (r=0.21), waist circumference (r=0.24), waist-hip ratio (r=0.20), leptin
      (r=0.32), and CRP (r=0.25). Participants with the highest AHEI scores tended to
      have 11.6% lower concentrations of irisin (P for trend =0.09), but they were not
      significant after adjustment for potential confounders. Better diet quality was
      associated with lower CRP concentrations (P for trend=0.02) in multivariate
      model. Percentage of energy from carbohydrate was inversely associated with CRP.
      CONCLUSIONS: Unlike CRP, irisin is not associated with dietary quality or
      quantity.

PMID- 24315780
TI  - Serum lipoprotein(a) complexes with beta2-glycoprotein I levels in patients with
      ischemic stroke.
AB  - BACKGROUND: We investigated serum lipoprotein(a) complexes with beta2
      glycoprotein I [beta2-GPI-Lp(a)] levels in ischemic stroke patients. METHODS:
      Serum beta2-GPI-Lp(a), oxidized Lp(a) [ox-Lp(a)] and Lp(a) levels were determined
      in 124 ischemic stroke patients and 64 normal controls. The severity and clinical
      outcome of ischemic stroke patients were evaluated by the National Institutes of
      Health Stroke Scale (NIHSS) and Barthel Index (BI), respectively. The correlation
      analysis and multiple linear regression analysis were performed. RESULTS:
      Compared with controls, serum beta2-GPI-Lp(a), ox-Lp(a) and Lp(a) levels were
      significantly increased in ischemic stroke patients, and their levels were higher
      in severe stroke than in mild stroke. The beta2-GPI-Lp(a) levels were positively
      related with ox-Lp(a) (r=0.665, P=0.000) and Lp(a) (r=0.195, P=0.035). NIHSS
      scores were positively correlated with beta2-GPI-Lp(a) (r=0.322, P=0.000), while
      BI was negatively related with beta2-GPI-Lp(a) (r=-0.301, P=0.012). Multiple
      linear regression analyses showed that beta2-GPI-Lp(a) (beta coefficient=0.338,
      P=0.010) and ox-Lp(a) (beta coefficient=0.265, P=0.043) were found to account for
      25.1% of the variation of NIHSS scores, and that only beta2-GPI-Lp(a) (beta
      coefficient=-0.351, P=0.005; adjusted R(2)=0.108) was an independent predictor of
      BI. CONCLUSIONS: Serum beta2-GPI-Lp(a) levels were increased in ischemic stroke
      patients. Elevated beta2-GPI-Lp(a) levels were associated with the severity and
      clinical outcome of ischemic stroke.

PMID- 24315781
TI  - Comparative evaluation of serum fluoride levels in patients with and without
      chronic abdominal pain.
AB  - BACKGROUND: Fluorosis ranks high among the major environmental health problems in
      India. Non-ulcer dyspeptic complaints are common in humans and it is a known fact
      that fluoride in drinking water, food and other items can cause these symptoms.
      METHODS: Fifty adult outpatients (mean age: 35.2+/-12.7 y) with chronic abdominal
      pain of unexplained origin were tested for their serum, urinary, and drinking
      water fluoride (F) concentrations. These concentrations were compared with those
      of 50 asymptomatic outpatients (mean age: 37.4+/-11.5 y) and analysed
      statistically. RESULTS: Serum F concentrations were higher than normal in 62% of
      the study group I and in 42% of the control group II with a mean of 0.065+/-0.03
      ppm (range: 0.010-0.421) in the former and 0.023+/-0.028 ppm in the latter.
      Statistical analysis of the data by Student's t-test (unpaired) revealed a
      significant correlation (p<0.05) between chronic abdominal pain and elevated
      serum F. Urinary fluoride concentrations in group I were 0.87+/-1.67 (0.01-3.7)
      ppm. Seventy-three percent of the patients examined for urinary fluoride
      concentrations were having higher values than normal, whereas 27% patients had
      normal range urinary fluoride concentrations despite raised serum fluoride
      concentrations. CONCLUSIONS: In the cases of chronic pain abdomen, chronic
      fluoride ingestion from drinking water and other sources can be the cause and
      should be evaluated in patients in which other parameters are normal.

PMID- 24315782
TI  - Psychiatric co-morbidity in problem and pathological gamblers: investigating the
      confounding influence of alcohol use disorder.
AB  - Pathological gambling is known to be associated with a higher than average
      prevalence of psychological co-morbidities including a range of psychiatric
      conditions. A problem with much of this literature, however, is that such
      problems are also frequently found in populations affected by alcohol use
      disorder, which is common in populations of pathological gamblers. Accordingly,
      the principal aim of this study was to profile the comorbidities present in a
      sample of pathological gamblers, comparing those who did, and did not,
      additionally meet criteria for alcohol use disorder. A sample of 140 community
      recruited regular gamblers completed a number of measures including the Mini
      International Neuropsychiatric Interview, the Personality Diagnostic
      Questionnaire, NORC DSM-IV Screen Self-Administered and the Alcohol Use Disorders
      Identification Test. Comparisons showed that most psychiatric conditions (and in
      particular personality disorders) were significantly more prevalent in those with
      a dual diagnosis, followed by problem gamblers and then by those with neither
      disorder. This suggests that high rates of psychiatric illness in pathological
      gambling may be strongly influenced by co-occurring alcohol problems. 

PMID- 24315783
TI  - Aripiprazole: a new risk factor for pathological gambling? A report of 8 case
      reports.
AB  - OBJECTIVE: It is commonly accepted that pathological gambling results from the
      interaction of multiple risk factors. Among these, dopamine replacement therapy
      (DRT) prescribed for Parkinson disease can be cited. Another dopamine agonist,
      aripiprazole, could be a new risk factor. We decided to explore this potential
      adverse drug reaction (ADR). METHOD: Based on a cohort of 166 pathological
      gamblers starting treatment in our department, data of each of the 8 patients
      treated by aripiprazole at inclusion were analyzed. RESULTS: The patients
      involved were schizophrenic or bipolar, mostly young men with a history of
      addictive disorders and regular gambling prior to the prescription of
      aripiprazole. For each one of them, the causality of aripiprazole was considered,
      using an algorithm. The probability that pathological gambling is actually due to
      aripiprazole is "possible" in 7 cases out of 8, and "doubtful" in one.
      CONCLUSIONS: Adverse drug reactions were confronted with other already published
      case reports. Dopamine partial agonist mechanism of aripiprazole could explain
      the occurrence of pathological gambling.

PMID- 24315784
TI  - Impact of renal dysfunction on the Seattle Heart Failure Model.
AB  - BACKGROUND: Renal dysfunction (RD) is a strong predictor of mortality in patients
      with heart failure (HF). However, its impact on the discrimination of the Seattle
      Heart Failure Model (SHFM) is poorly understood. METHODS: Serum creatinine (SCr)
      and creatinine clearance (CrCl) were reviewed for patients from four of the six
      cohorts originally used to derive and validate the SHFM. Patients were followed
      for death. The independent prediction of adding SCr or CrCl to the SHFM was
      assessed using multivariable Cox proportional hazards and the incremental value
      for prediction by changes in the ROC curves for 1- and 2-year event prediction.
      RESULTS: Among 7,146 patients (mean age 63 +/- 11 years), 1,511 deaths occurred
      during a mean follow-up of 2.04 years. SCr and CrCl had a modest positive
      correlation with SHFM (r = 0.30, p = 0.002). In combination with SHFM, SCr
      (hazard ratio [HR] per mg/dl 1.25, 95% CI 1.13 to 1.38, p < 0.0001) and CrCl (HR
      per 10 ml/min 0.95, 95% CI 0.93 to 0.97, p < 0.0001) were both multivariable
      predictors of events. When stratified by absolute risk based on the SHFM, SCr or
      CrCl provided more additional information in lower risk patients and less or no
      additional information in higher risk patients. The addition of SCr and the
      SHFM*SCr, or CrCl and the SHFM*CrCl interaction to the SHFM was associated with
      almost no change in the 1- and 2-year area under ROC curves for the SHFM score.
      CONCLUSIONS: Compared with the SHFM alone, RD is independently predictive of
      mortality only in lower risk patients. Overall discrimination is only minimally
      improved with addition of SCr or CrCl to the SHFM.

PMID- 24315786
TI  - Myocardial calcification after orthotopic heart transplantation.

PMID- 24315785
TI  - Dynamic patterns of ventricular remodeling and apoptosis in hearts unloaded by
      heterotopic transplantation.
AB  - BACKGROUND: Mechanical unloading of failing hearts can trigger functional
      recovery but results in progressive atrophy and possibly detrimental adaptation.
      In an unbiased approach, we examined the dynamic effects of unloading duration on
      molecular markers indicative of myocardial damage, hypothesizing that potential
      recovery may be improved by optimized unloading time. METHODS: Heterotopically
      transplanted normal rat hearts were harvested at 3, 8, 15, 30, and 60 days. Forty
      seven genes were analyzed using TaqMan-based microarray, Western blot, and
      immunohistochemistry. RESULTS: In parallel with marked atrophy (22% to 64% volume
      loss at 3 respectively 60 days), expression of myosin heavy-chain isoforms (MHC
      alpha/-beta) was characteristically switched in a time-dependent manner. Genes
      involved in tissue remodeling (FGF-2, CTGF, TGFb, IGF-1) were increasingly
      upregulated with duration of unloading. A distinct pattern was observed for genes
      involved in generation of contractile force; an indiscriminate early
      downregulation was followed by a new steady-state below normal. For pro-apoptotic
      transcripts bax, bnip-3, and cCasp-6 and -9 mRNA levels demonstrated a slight
      increase up to 30 days unloading with pronunciation at 60 days. Findings
      regarding cell death were confirmed on the protein level. Proteasome activity
      indicated early increase of protein degradation but decreased below baseline in
      unloaded hearts at 60 days. CONCLUSIONS: We identified incrementally increased
      apoptosis after myocardial unloading of the normal rat heart, which is
      exacerbated at late time points (60 days) and inversely related to loss of
      myocardial mass. Our findings suggest an irreversible detrimental effect of long
      term unloading on myocardium that may be precluded by partial reloading and
      amenable to molecular therapeutic intervention.

PMID- 24315787
TI  - Impact of pre-diabetes on heart transplant outcomes in patients with advanced
      heart failure.

PMID- 24315788
TI  - Area under the concentration-time curve to minimum inhibitory concentration ratio
      as a predictor of vancomycin treatment outcome in methicillin-resistant
      Staphylococcus aureus bacteraemia.
AB  - There have been few clinical studies on the association between the 24-h area
      under the concentration-time curve (AUC24) to minimum inhibitory concentration
      (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant
      Staphylococcus aureus (MRSA) infections. Patients with MRSA bacteraemia between
      July 2009 and January 2012 were analysed retrospectively. All adult patients
      treated with vancomycin for >=72 h without dialysis were included. The MIC was
      determined by Etest and broth microdilution (BMD). Initial steady-state AUC24 was
      estimated using a Bayesian model, and the AUC24/MIC cut-off value for
      differentiating treatment success and failure was calculated by classification
      and regression tree (CART) analysis. In total, 76 patients were enrolled;
      vancomycin treatment failure occurred in 20 patients (26.3%). Catheter-related
      infection was the most frequent (35.5%), followed by surgical site infection
      (26.3%), whilst 25 (32.9%) had complicated infections. In univariate analysis,
      decreased MRSA vancomycin susceptibility (MIC>=1.5 mg/L) and vancomycin trough
      levels (15-20 mg/L) were not associated with treatment outcomes. In the CART
      analysis, low initial vancomycin AUC24/MIC (<430 by Etest; <398.5 by BMD) was
      associated with a higher treatment failure rate (50.0% vs. 25.0%, P=0.039 by
      Etest; 45.0% vs. 23.2%; P=0.065 by BMD). In multivariate analysis, low initial
      vancomycin AUC24/MIC was a significant risk factor for treatment failure
      [adjusted odds ratio (aOR)=4.39, 95% confidence interval (CI), 1.26-15.35 by
      Etest; aOR=3.73, 95% CI 1.10-12.61 by BMD]. In MRSA bacteraemia, a low initial
      vancomycin AUC24/MIC is an independent risk factor for vancomycin treatment
      failure.

PMID- 24315789
TI  - Bactericidal effect of colistin on planktonic Pseudomonas aeruginosa is
      independent of hydroxyl radical formation.
AB  - The bactericidal effect of several major types of antibiotics has recently been
      demonstrated to be dependent on the formation of toxic amounts of hydroxyl
      radicals (OH.) resulting from oxidative stress in metabolically active cells.
      Since killing by the antimicrobial peptide colistin does not require bacterial
      metabolic activity, we tested whether the bactericidal effect of colistin depends
      on the formation of OH.. In Pseudomonas aeruginosa cultures, OH-mediated killing
      by ciprofloxacin was demonstrated by decreased bacterial survival and induction
      of 3'-(p-hydroxyphenyl) fluorescein (HPF) fluorescence. OH.-mediated killing by
      ciprofloxacin was further confirmed by rescue of cells and reduction of HPF
      fluorescence due to prevention of OH. accumulation by scavenging with thiourea,
      by chelating with dipyridyl, by decreasing metabolism as well as by anoxic
      growth. In contrast, no formation of OH. was seen in P. aeruginosa during killing
      by colistin, and prevention of OH. accumulation could not rescue P. aeruginosa
      from killing by colistin. These results therefore demonstrate that the
      bactericidal activity of colistin on P. aeruginosa is not dependent on oxidative
      stress. In conclusion, antimicrobial peptides that do not rely on OH. formation
      should be considered for treatment of Gram-negative bacteria growing at low
      oxygen tension such as in endobronchial mucus and paranasal sinuses in cystic
      fibrosis patients, in abscesses and in infectious biofilm.

PMID- 24315790
TI  - In vitro and intracellular activities of fosfomycin against clinical strains of
      Listeria monocytogenes.
AB  - This study was designed to evaluate the potential role of fosfomycin as a
      therapeutic agent in human listeriosis. The in vitro activity of fosfomycin
      against 154 Listeria monocytogenes clinical isolates under conditions that mimic
      the induction of prfA expression was determined and was correlated with
      fosfomycin intracellular antimicrobial activity. In vitro, partial induction of
      prfA expression is achieved through bacterial growth in brain-heart infusion agar
      supplemented with activated charcoal (BHIC). A fosfomycin
      pharmacokinetic/pharmacodynamic breakpoint of <=64 mg/L was estimated using a
      Monte Carlo simulation to assess the success of an intravenous fosfomycin dose of
      300 mg/kg/day over 5000 individuals. Eighty strains (51.9%) were susceptible to
      fosfomycin in BHIC, with minimum inhibitory concentrations (MICs) of <=64 mg/L;
      13 strains (8.4%) had the epidemic clone (EC) marker. In addition, 27 strains
      (17.5%) had a three doubling dilutions reduction in the MIC from >=1024 mg/L to
      128 mg/L (96-128 mg/L by Etest). The fosfomycin modal MIC is lower under prfA
      expression. However, this effect is smaller in terms of clinical categorisation
      of isolates and can be influenced by the serotype and clonal type. In A549 cells,
      the reductions in bacterial inocula of the two susceptible isolates studied after
      1h and 24h of incubation with fosfomycin at 0.5* the human maximum serum
      concentration (Cmax) were 45.8% and 46.6%, and 93.8% and 99.1%, respectively.
      Slightly higher reductions were found with fosfomycin at 1* Cmax. The resistant
      strain tested showed significantly lower reductions in all assays.

PMID- 24315791
TI  - Patient safety certification in a Department of Intensive Care Medicine: our
      experience with standard UNE 179003:2013.
AB  - Systematic and structured methods must be used to ensure that healthcare risks
      are effectively managed. Spanish standard UNE 179003:2013 provides healthcare
      organizations with a framework and a systematic protocol for managing patient
      safety from a clinical and organizational perspective. Furthermore, it is useful
      in securing an efficient balance among health risk, health outcomes and costs.
      The UNE 179003:2013 certifies that a clinical service complies with rules and
      operating procedures aimed at reducing the incidence of adverse events. It also
      requires mandatory continuous improvement, given that the standard entails
      frequent monitoring of the risk management system through periodic audits. The
      aims of this paper are to describe the UNE 179003:2013 certification process in
      an Intensive Care Unit, propose a risk management program for critical patients,
      and offer some recommendations regarding its implementation.

PMID- 24315793
TI  - Inhibitory activity and mechanism of two scorpion venom peptides against herpes
      simplex virus type 1.
AB  - Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen that causes
      severe diseases, but there are not effective and safe drugs in clinical therapy
      besides acyclovir (ACV) and related nucleoside analogs. In this study, two new
      venom peptides from the scorpion Heterometrus petersii were identified with
      effective inhibitory effect on HSV-1 infection in vitro. Both Hp1036 and Hp1239
      peptides exhibited potent virucidal activities against HSV-1 (EC50=0.43+/-0.09
      and 0.41+/-0.06MUM, respectively) and effective inhibitory effects when added at
      the viral attachment (EC50=2.87+/-0.16 and 5.73+/-0.61MUM, respectively), entry
      (EC50=4.29+/-0.35 and 4.32+/-0.47MUM, respectively) and postentry (EC50=7.86+/
      0.80 and 8.41+/-0.73MUM, respectively) steps. Both Hp1036 and Hp1239 peptides
      adopted alpha-helix structure in approximate membrane environment and resulted in
      the destruction of the viral morphology. Moreover, Hp1036 and Hp1239 peptides
      entered Vero cells and reduced the intracellular viral infectivity. Taken
      together, Hp1036 and Hp1239 peptides are two anti-viral peptides with effective
      inhibitory effect on multiple steps of HSV-1 life cycle and therefore are good
      candidate for development as virucides. 

PMID- 24315792
TI  - Pro-inflammatory stimulation of meniscus cells increases production of matrix
      metalloproteinases and additional catabolic factors involved in osteoarthritis
      pathogenesis.
AB  - OBJECTIVE: Meniscus injury increases the risk of osteoarthritis; however, the
      biologic mechanism remains unknown. We hypothesized that pro-inflammatory
      stimulation of meniscus would increase production of matrix-degrading enzymes,
      cytokines and chemokines which cause joint tissue destruction and could
      contribute to osteoarthritis development. DESIGN: Meniscus and cartilage tissue
      from healthy tissue donors and total knee arthroplasties (TKAs) was cultured.
      Primary cell cultures were stimulated with pro-inflammatory factors [IL-1beta, IL
      6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real
      time PCR, protein arrays and immunoblots. To determine if NF-kappaB was required
      for MMP production, meniscus cultures were treated with inflammatory factors with
      and without the NF-kappaB inhibitor, hypoestoxide. RESULTS: Normal and
      osteoarthritic meniscus cells increased their MMP secretion in response to
      stimulation, but specific patterns emerged that were unique to each stimulus with
      the greatest number of MMPs expressed in response to FnF. Meniscus collagen and
      connective tissue growth factor (CTGF) gene expression was reduced. Expression of
      cytokines (IL-1alpha, IL-1beta, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and
      components of the NF-kappaB and tumor necrosis factor (TNF) family were
      significantly increased. Cytokine and chemokine protein production was also
      increased by stimulation. When primary cell cultures were treated with
      hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was
      reduced as were MMP-1 and MMP-3 production. CONCLUSIONS: Pro-inflammatory
      stimulation of meniscus cells increased matrix metalloproteinase production and
      catabolic gene expression. The meniscus could have an active biologic role in
      osteoarthritis development following joint injury through increased production of
      cytokines, chemokines, and matrix-degrading enzymes.

PMID- 24315794
TI  - Lower extremity mobility limitation and impaired muscle function in women with
      ulcerative colitis.
AB  - BACKGROUND AND AIM: Fatigue, weakness and musculoskeletal manifestations are
      associated with IBD. An impaired nutritional status and a reduced physical
      activity can contribute to these clinical outcomes, impacting quality of life and
      increasing disability. This study aims to assess muscle strength and lower limb
      physical performance in female UC patients, taking into consideration disease
      activity, body composition and habitual physical activity. METHODS: A case
      control study was performed including 23 UC female outpatients and 23 age- and
      BMI-matched healthy women as controls. Quadriceps strength (QS), handgrip
      strength (HGS), physical performance based measures (five repetitions sit-up test
      and 4meter gait speed test), body composition (bioelectrical impedance analysis,
      anthropometry), and habitual physical activity (HPA) levels were assessed.
      RESULTS: UC group had decreased QS (-6%; P=0.012), slower sit-up test (-32%;
      P=0.000), slower gait speed (-17% P=0.002) and decreased HPA level (-30%,
      P=0.001) compared with controls. No difference in HGS was observed between
      groups. Logistic regression showed that UC was an independent factor for
      decreased QS and slower sit-up test, while HPA was a protective factor for
      impaired gait speed. Multivariate linear regression showed that BMI was
      independently associated with an improved QS and slower sit-up test in the UC
      group. CONCLUSION: Women with UC had decreased lower limb strength and mobility
      limitations, which were associated with BMI and the level of physical activity.
      Early evaluation of nutritional status and performance of the lower limbs could
      identify UC patients with pre-clinical disability who may benefit from earlier
      health lifestyle modifications.

PMID- 24315796
TI  - Detection of TS polyomavirus DNA in tonsillar tissues of children and adults:
      evidence for site of viral latency.
AB  - BACKGROUND: The trichodysplasia spinulosa-associated polyomavirus (TSPyV), a
      recently discovered species of the family Polyomaviridae, is associated with
      development of trichodysplasia spinulosa (TS), a rare follicular skin disease of
      immunocompromised individuals. The viral seroprevalence in the general population
      is ~70%, with little known of its route of transmission, latency, or primary
      infection site. OBJECTIVES: We aimed to determine whether the viral DNA is
      detectable in tonsillar tissue of constitutionally healthy individuals, and what
      the corresponding antiviral seroreactivities are. STUDY DESIGN: We tested 229
      matched pairs of tonsillar tissue biopsies and serum samples from asymptomatic
      donors for TSPyV DNA by real-time quantitative PCR with primer pairs and Taq-Man
      probes targeting the VP1 and LT genes. The sera were studied by enzyme
      immunoassay (EIA) for TSPyV-VP1-IgG and the PCR-positive individuals also for 
      IgM and -IgG-avidity. RESULTS: TSPyV DNA was detectable in 8 (3.5%) of 229
      tonsillar tissues, and in none of the corresponding sera. TSPyV IgG
      seroprevalence among children was 39% and among adults 70%. Each of the 8 PCR
      positive subjects had antiviral IgG of high avidity but not IgM. CONCLUSIONS:
      TSPyV PCR positivity of tonsillar samples of individuals with long-term immunity
      provides the first evidence of TSPyV in tonsils and suggests lymphoid tissue as a
      latency site of this emerging human pathogen.

PMID- 24315795
TI  - Environmental factors in a population-based inception cohort of inflammatory
      bowel disease patients in Europe--an ECCO-EpiCom study.
AB  - BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is
      increasing in Eastern Europe possibly due to changes in environmental factors
      towards a more "westernised" standard of living. The aim of this study was to
      investigate differences in exposure to environmental factors prior to diagnosis
      in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a
      population-based, prospective inception cohort of 1560 unselected IBD patients
      from 31 European countries covering a background population of 10.1 million. At
      the time of diagnosis patients were asked to complete an 87-item questionnaire
      concerning environmental factors. RESULTS: A total of 1182 patients (76%)
      answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%)
      ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences
      regarding smoking status, caffeine intake, use of oral contraceptives, or number
      of first-degree relatives with IBD were found. Sugar intake was higher in CD and
      UC patients from Eastern Europe than in Western Europe while fibre intake was
      lower (p<0.01). Daily consumption of fast food as well as appendectomy before the
      age of 20 was more frequent in Eastern European than in Western European UC
      patients (p<0.01). Eastern European CD and UC patients had received more
      vaccinations and experienced fewer childhood infections than Western European
      patients (p<0.01). CONCLUSIONS: In this European population-based inception
      cohort of unselected IBD patients, Eastern and Western European patients differed
      in environmental factors prior to diagnosis. Eastern European patients exhibited
      higher occurrences of suspected risk factors for IBD included in the Western
      lifestyle.

PMID- 24315797
TI  - The relationship between the cervical and anal HPV infection in women with
      cervical intraepithelial neoplasia.
AB  - BACKGROUND: More than 90% of cases of anal cancers are caused by high-risk human
      papillomavirus (HR HPV) infection and a history of cervical intraepithelial
      neoplasia (CIN) is established as possible risk factor. OBJECTIVES: To
      demonstrate relationship between anal and cervical HPV infection in women with
      different grades of CIN and microinvasive cervical cancer. STUDY DESIGN: A total
      of 272 women were enrolled in the study. The study group included 172 women who
      underwent conization for high-grade CIN or microinvasive cervical cancer. The
      control group consisted of 100 women with non-neoplastic gynecologic diseases or
      biopsy-confirmed CIN 1. All participants completed a questionnaire detailing
      their medical history and sexual risk factors and were subjected to anal and
      cervical HPV genotyping using Cobas and Lynear array HPV test. RESULTS: Cervical,
      anal, and concurrent cervical and anal HPV infections were detected in 82.6%,
      48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of
      women in the control group, respectively. The prevalence of the HR HPV genotypes
      was higher in the study group and significantly increased with the severity of
      cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold
      more often in the study group than in the control group. Any contact with the
      anus was the only significant risk factor for development of concurrent HPV
      infection. CONCLUSIONS: Concurrent anal and cervical HR HPV infection was found
      in nearly half of women with CIN 2+. The dominant genotype found in both
      anatomical locations was HPV 16. Any frequency and any type of contact with the
      anus were shown as the most important risk factor for concurrent HPV infection.

PMID- 24315798
TI  - Force dynamics in fixed-ratio schedules.
AB  - Fixed-ratio schedules are widely used in behavioral research. Although fixed
      ratio schedules often conjure up relationships to work and effort, little is
      known about effort-related measures in these schedules. Early research had shown
      that force and effort of operant behavior vary systematically during the
      execution of ratio schedules, and the goal of the present study was to revisit
      early research on force dynamics in fixed-ratio schedules. Four rats earned
      sucrose by pressing an isometric force transducer. Presses produced sucrose after
      ten or twenty responses. In general, the force of responses increased then
      decreased systematically across the ratio. The possibility that decreases in
      force during ratio execution was due to a trade-off with the differential
      reinforcement of short inter-response times (IRT) was investigated in an
      additional condition where sucrose was made available according to a tandem fixed
      ratio 19 inter-response (IRT)> t schedule. The tandem IRT requirement did not
      eliminate decreasing trends in force across the ratio; unexpectedly, the tandem
      requirement did eliminate increases in force early in the ratio, which may
      reflect sequence-level organization operating in the control of force dynamics. 

PMID- 24315799
TI  - Consequences of the instar stage for behavior in a pit-building antlion.
AB  - Pit-building antlion larvae are opportunistic predators that dig conical pits in
      loose soils, and prey on small arthropods that fall into their traps. We
      investigated different behavioral traits of second and third instar larvae
      selected for similar body masses, while also exploring the behavioral consistency
      and personalities of the third instar stage. Second instar larvae constructed
      smaller pits than third instar larvae. The former also responded more slowly to
      prey and exploited prey less efficiently. Notably, all these instar-based
      differences disappeared after molting into the third instar stage. In addition,
      third instar larvae exhibited consistent behavior in their pit size, response
      times to prey and to less extent in relocation distances. We detected two axes of
      behavior. The first axis included a correlation between pit size, response time
      and prey exploitation efficiency, thus reflecting investment in foraging
      activity. The second axis seemed to represent a trade-off between response time
      and relocation distance, implying that individuals that responded more slowly to
      prey, relocated over larger distances. These results point to coordinated
      behavior reflecting different levels of investment in foraging, while also
      emphasizing the importance of instar stage, in addition to body mass, when
      studying the behavior of such organisms characterized by a complex life cycle. 

PMID- 24315800
TI  - Estimates of genetic parameters for fatty acids in brisket adipose tissue of
      Canadian commercial crossbred beef steers.
AB  - Heritability and genetic and phenotypic correlations between 15 individuals and
      10 groups of fatty acids with a concentration greater than 0.5% in the brisket
      adipose tissue of 223 Angus and Charolais based crossbred commercial steers were
      estimated using univariate and bivariate animal models. Individual saturated
      fatty acids were low to moderately heritable, with heritability estimates ranging
      from 0.05 (C16:0) to 0.31 (C15:0). Individual monounsaturated fatty acids were
      low to moderately highly heritable ranging from 0.04 (9c C17:1 and 11c C18:1) to
      0.51 (9c C14:1). Polyunsaturated fatty acid C18:2n-6 was moderately heritable
      (0.17). Among groups of fatty acids, heritability estimates ranged from 0.03 for
      branched chain fatty acid (BCFA) and n-6/n-3 to 0.16 for n-6 and Health Index. A
      range of low (0.00) to high (1.00) phenotypic and genetic correlations was
      observed among the 25 fatty acids considered in this study. In general, fatty
      acids such as conjugated linoleic acid (CLA) and 11t C18:1, with potential health
      benefits, showed significant antagonistic correlations with unhealthy fatty acids
      such as C14:0 and C16:0. The results from this study provide insight into the
      direct genetic control of host genes on fatty acid composition of beef tissues
      and will facilitate designs of genetic selection and/or genetic based diet
      management to improve fatty acid composition in beef cattle. 

PMID- 24315801
TI  - Lessons raised by the major 2010 dengue epidemics in the French West Indies.
AB  - Dengue fever has been endemo-epidemic in the whole Region of America. In 2010,
      Guadeloupe and Martinique experienced historical epidemics, with an estimated
      attack rate of 10% in two islands. When considering the temporal evolution of
      epidemiological indicators, an unusual increase in the number of dengue cases
      could be detected very early. Two main factors might have facilitated the
      settlement of a viral transmission despite the dry season: a low immunity of the
      population against the circulating serotype and particular climatic conditions,
      notably very high temperatures which could have improved both virus and vector
      efficiency. This unusual situation was considered as a warning sign, and indeed
      led to major outbreaks in both islands a few weeks later. This event underlines
      that follow-up of epidemiological indicators is necessary to detect the unusual
      situations as soon as possible. Furthermore, development of biological and
      modelling tools should be promoted, as well as integrated management strategies
      for dengue prevention and control. 

PMID- 24315802
TI  - Safety and effectiveness of ferumoxytol in hemodialysis patients at 3 dialysis
      chains in the United States over a 12-month period.
AB  - BACKGROUND: Intravenous (IV) iron is the treatment of choice for iron-deficiency
      anemia (IDA) in patients with dialysis-dependent chronic kidney disease (DD-CKD).
      However, IV iron products have been associated with serious adverse events
      (SAEs), including anaphylactoid reactions. Ferumoxytol is an IV iron preparation
      that can be injected over a short period of time. Although randomized clinical
      trials support ferumoxytol's efficacy and safety, additional insights may be
      drawn from the acquisition of long-term, repeat dosing efficacy and safety data
      in a real-world setting. OBJECTIVE: The goal of this study was to characterize
      the effectiveness and safety profile of ferumoxytol as administered to adult DD
      CKD patients with IDA in a real-world setting. The ability of ferumoxytol to
      maintain hemoglobin (Hb), transferrin saturation (TSAT), and ferritin treatment
      targets established by the 2006 Kidney Disease Outcomes Quality Initiative
      guidelines was determined in 3 medium-sized US-based dialysis chains. METHODS:
      This retrospective, observational study was conducted to examine laboratory and
      dosing data for all patients who received any dose of ferumoxytol at 3 US-based
      dialysis chains over a 12-month period. Investigators and/or physicians from each
      of the chains also made independent determinations regarding the seriousness of
      any adverse event (AE). Special attention was paid to the incidence and types of
      AEs and SAEs that were potentially associated with ferumoxytol. RESULTS: Over the
      12-month observation period, 8666 patients (mean [SD] age in chains A, B and C,
      63.9 [14.8], 63.9 [14.9] and 63.6 [15.1], respectively), were treated with 33,358
      doses of ferumoxytol across the 3 chains. Treatment with ferumoxytol corresponded
      to an increased mean monthly Hb level relative to baseline (0.13-0.69 g/dL) and
      led to an increase in the proportion of patients maintained within the target Hb
      range of 10 to 12 g/dL (61%-72%). Ferumoxytol was also associated with increases
      in TSAT and ferritin that stabilized throughout the observation period. Incidence
      of AEs was similar across the 3 chains; between 0.07% and 1.77% of all patients
      treated at each chain experienced an AE associated with ferumoxytol
      administration. SAEs were reported in 0.2% of patients. The most common AEs
      reported (>=6 patients) were nausea (0.37% of patients), pruritus (0.29%),
      vomiting (0.25%), hypotension (0.21%), and dyspnea (0.20%). Two patients (0.02%)
      experienced anaphylactoid reactions. The AE profile of ferumoxytol remained
      consistent with that reported from controlled clinical trials. CONCLUSIONS: These
      long-term data, which include repeat dosing in a large number of DD-CKD patients
      with IDA in a real-world setting, confirm the effectiveness of ferumoxytol in
      increasing and maintaining Hb levels within the target range and with favorable
      assessments of long-term safety.

PMID- 24315803
TI  - The interaction of lexical tone, intonation and semantic context in on-line
      spoken word recognition: an ERP study on Cantonese Chinese.
AB  - In two ERP experiments, we investigate the on-line interplay of lexical tone,
      intonation and semantic context during spoken word recognition in Cantonese
      Chinese. Experiment 1 shows that lexical tone and intonation interact
      immediately. Words with a low lexical tone at the end of questions (with a rising
      question intonation) lead to a processing conflict. This is reflected in a low
      accuracy in lexical identification and in a P600 effect compared to the same
      words at the end of a statement. Experiment 2 shows that a strongly biasing
      semantic context leads to much better lexical-identification performance for
      words with a low tone at the end of questions and to a disappearance of the P600
      effect. These results support the claim that semantic context plays a major role
      in disentangling the tonal information from the intonational information, and
      thus, in resolving the on-line conflict between intonation and tone. However, the
      ERP data indicate that the introduction of a semantic context does not entirely
      eliminate on-line processing problems for words at the end of questions. This is
      revealed by the presence of an N400 effect for words with a low lexical tone and
      for words with a high-mid lexical tone at the end of questions. The ERP data thus
      show that, while semantic context helps in the eventual lexical identification,
      it makes the deviation of the contextually expected lexical tone from the actual
      acoustic signal more salient. 

PMID- 24315804
TI  - Short-term functional outcome and premorbid adjustment in clinical high-risk
      patients. Results of the EPOS project.
AB  - PURPOSE: In patients with schizophrenia, premorbid psychosocial adjustment is an
      important predictor of functional outcome. We studied functional outcome in young
      clinical high-risk (CHR) patients and how this was predicted by their childhood
      to adolescence premorbid adjustment. METHODS: In all, 245 young help-seeking CHR
      patients were assessed with the Premorbid Adjustment Scale, the Structured
      Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness
      Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general
      symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self
      experienced basic symptoms; they were carried out at baseline, at 9-month and 18
      month follow-up. Transitions to psychosis were identified. In the hierarchical
      linear model, associations between premorbid adjustment, background data,
      symptoms, transitions to psychosis and GAF scores were analysed. RESULTS: During
      the 18-month follow-up, GAF scores improved significantly, and the proportion of
      patients with poor functioning decreased from 74% to 37%. Poor premorbid
      adjustment, single marital status, poor work status, and symptoms were associated
      with low baseline GAF scores. Low GAF scores were predicted by poor premorbid
      adjustment, negative, positive and basic symptoms, and poor baseline work status.
      The association between premorbid adjustment and follow-up GAF scores remained
      significant, even when baseline GAF and transition to psychosis were included in
      the model. CONCLUSION: A great majority of help-seeking CHR patients suffer from
      deficits in their functioning. In CHR patients, premorbid psychosocial
      adjustment, baseline positive, negative, basic symptoms and poor
      working/schooling situation predict poor short-term functional outcome. These
      aspects should be taken into account when acute intervention and long-term
      rehabilitation for improving outcome in CHR patients are carried out.

PMID- 24315805
TI  - [Premature immunosenescence in triple-transgenic mice for Alzheimer's disease].
AB  - INTRODUCTION: A deterioration of the neuroimmunoendocrine network has been
      observed in Alzheimer's disease (AD). However, the peripheral immune response has
      hardly been investigated in this pathology. Since some immune function parameters
      have been established as good markers of the rate of ageing, and can predict
      longevity, the aim of the present work was to study some of these functions in
      splenic leucocytes in transgenic mice for AD of different ages. MATERIAL AND
      METHODS: Young female (4 +/- 1 months), adult (9 +/- 1 months), and mature (12 +/
      1 months) triple-transgenic mice for AD (3 xTgAD) and non-transgenic (NTg)
      control mice of the same ages were used. The chemotaxis, the anti-tumour activity
      of " natural killer " (NK) cells and the lymphoproliferative response in the
      presence of the mitogens concanavalin A and lipopolysaccharide, functions that
      decrease with age, were determined in splenic leucocytes. In addition, the
      differences in lifespan between 3 xTgAD and NTg were studied in parallel using
      other animals, until their death through natural causes. RESULTS: In 3 xTgAD,
      with respect to NTg, chemotaxis decreased at all ages studied, whereas in
      lymphoproliferative response this reduction was shown at 4 months and 9 months.
      NK activity was diminished only in young 3 xTgAD with respect to NTg. The 3 xTgAD
      showed a shorter lifespan than the NTg control group. CONCLUSIONS: The 3 xTgAD
      mice show a premature immunosenescence, which could explain their early
      mortality. The determination of these immune functions at peripheral level could
      serve as a marker of the progression of the Alzheimer's disease.

PMID- 24315806
TI  - Bacterial diversity associated with feeding dry forage at different dietary
      concentrations in the rumen contents of Mehshana buffalo (Bubalus bubalis) using
      16S pyrotags.
AB  - Pyrosequencing of 16S rRNA gene targeting bacteria was applied to identify diet
      induced shifts in the microbiome of both solid and liquid ruminal fractions
      retrieved from water buffalo fed different diets. The depth of coverage of
      metabolically active bacteria in a community using different primer pairs was
      also investigated. To assess reproducibility, animal to animal variation was
      considered in all phylogenetic and community comparisons. The experiment included
      four non-lactating water buffaloes fed three different diets for six weeks each;
      diets were M1 (50% concentrate: 50% dry roughage), M2 (25% concentrate: 75% dry
      roughage) and M3 (100% dry roughage). A total of 333, 851 pyrotags were analyzed
      in this study. Phylogenetic analysis revealed significant differences in the
      rumen microbiome mediated by primer and diet (P < 0.05). Differences in community
      composition due to primer, diet, fraction and animal were compared using
      unweighted and weighted UniFrac analysis. Clustering of communities was largely
      explained by primer differences in both weighted and unweighted UniFrac analyses
      (P < 0.001). In the weighted analysis, communities clustered by diets (P < 0.05)
      and fractions (P < 0.08) while no inter-animal variation was observed. The
      identified repertoire of bacterial populations was dependent on the primer pair,
      as targeting the V4-V5 region resulted in greater diversity profiles of the
      microbiome. Within each primer pair, dietary changes altered the community
      composition with noticeable shifts at genus level. Genera such as Ruminococcus
      and Fibrobacter (P < 0.05) were higher in abundance on M3 diet while Prevotella
      dominated (P < 0.05) on M1 diet.

PMID- 24315807
TI  - Lactulose promotes equol production and changes the microbial community during in
      vitro fermentation of daidzein by fecal inocula of sows.
AB  - Equol has higher biological effects than other isoflavones. However, only about
      30-50% of humans possess a microbiota capable of producing equol from dietary
      daidzein. In recent years, interest has grown in dietary applications to improve
      equol production in human and other animals. In this study, lactulose was used as
      a potential equol-promoting prebiotic in vitro. The effect of lactulose on
      transformation of daidzein into equol by sows' fecal microbiota was investigated.
      Results showed that lactulose treatment improved bacteria growth parameters,
      changing the kinetics of fermentation in vitro. Lactulose significantly increased
      total gas production, T1/2, Tmax, and Rmax. Furthermore, lactulose altered the
      microflora composition, increased equol production associated with a reduction in
      the population of methanogen and increased the sulfate-reducing bacteria
      population during 24 h of incubation. Here, we report for the first time that in
      a certain condition (sealing or high pressure), via a dihydrodaidzein (DHD)
      pathway equol might be able to reform to daidzein by further metabolism using
      lactulose as a substrate. This study proposes that "hydrogen-producing prebiotic"
      might be a novel way to promote equol production in vivo or in vitro. 

PMID- 24315808
TI  - Prebiotic effects of almonds and almond skins on intestinal microbiota in healthy
      adult humans.
AB  - Almonds and almond skins are rich in fiber and other components that have
      potential prebiotic properties. In this study we investigated the prebiotic
      effects of almond and almond skin intake in healthy humans. A total of 48 healthy
      adult volunteers consumed a daily dose of roasted almonds (56 g), almond skins
      (10 g), or commercial fructooligosaccharides (8 g) (as positive control) for 6
      weeks. Fecal samples were collected at defined time points and analyzed for
      microbiota composition and selected indicators of microbial activity. Different
      strains of intestinal bacteria had varying degrees of growth sensitivity to
      almonds or almond skins. Significant increases in the populations of
      Bifidobacterium spp. and Lactobacillus spp. were observed in fecal samples as a
      consequence of almond or almond skin supplementation. However, the populations of
      Escherichia coli did not change significantly, while the growth of the pathogen
      Clostridum perfringens was significantly repressed. Modification of the
      intestinal microbiota composition induced changes in bacterial enzyme activities,
      specifically a significant increase in fecal beta-galactosidase activity and
      decreases in fecal beta-glucuronidase, nitroreductase and azoreductase
      activities. Our observations suggest that almond and almond skin ingestion may
      lead to an improvement in the intestinal microbiota profile and a modification of
      the intestinal bacterial activities, which would induce the promotion of health
      beneficial factors and the inhibition of harmful factors. Thus we believe that
      almonds and almond skins possess potential prebiotic properties. 

PMID- 24315809
TI  - Molecular monitoring of the bacterial community structure in foal feces pre- and
      post-weaning.
AB  - This study assessed the time-scale variability of bacterial community structure
      in foal feces from birth to 365 days of age using Automated Ribosomal Intergenic
      Spacer Analysis (ARISA). Fecal samples were collected from five foals 2 h after
      birth (meconium) and in the morning at days 1, 2, 5, 10, 30, 60, 120, 179, 183,
      194 and 365. The ARISA profiles were compared using an analysis of similarity
      (ANOSIM). Although both the age effect and the foal effect were highly
      significant (P < 0.010), the R-ANOSIM value for the foal effect was very low (R
      ANOSIM = 0.089), while that of the age effect was much higher (R-ANOSIM = 0.309).
      Significant age-related changes were detected between days 0 and 2 (R-ANOSIM =
      0.500), days 2 and 10 (R-ANOSIM = 0.475) and days 10 and 30 (R-ANOSIM = 0.519).
      No further shifts between consecutive times of sampling were detected in the
      bacterial community after day 30 and no changes were observed at weaning (day
      180). These results show that the establishment of the intestinal bacterial
      community in foals is a sequential process, which reaches its climax state at
      around one month of age. Further studies using new generation sequencing based
      methods could be conducted to identify which bacterial genera are establishing in
      foals during the first month of life. 

PMID- 24315811
TI  - Maturational changes of neonatal electroencephalogram: a comparison between intra
      uterine and extra uterine development.
AB  - OBJECTIVES: To evaluate electroencephalogram (EEG) patterns in very low birth
      weight premature newborns when reaching term-to-term neonates, thereby comparing
      extra uterine to intra uterine development. METHODS: EEG recordings were obtained
      between 2 and 14 days of life in 47 preterm (<37 weeks) very low birth weight
      (?1500 g) newborns and repeated when reaching term age (38-42 weeks) in a
      subsample (n=22). EEG recordings were also obtained in term newborns. Clinical
      evaluation was performed at birth and at 6 and 12 months. RESULTS: Relative to
      the first EEG, preterm newborns showed a reduction in delta brushes and
      interburst intervals and increased interhemispheric synchrony, suggesting an
      improvement in EEG maturation. Further organization in sleep patterns, like a
      reduction in total sleep time and phase shifts, were also observed. However, when
      reaching term, preterm newborns still had less mature EEG patterns, phase shifts
      and transitional sleep than matched controls. Background abnormalities and
      dysmaturity in preterm newborns during the first EEG predicted adverse
      neurological outcome later on. CONCLUSIONS: EEG patterns in preterm very low
      birth weight newborns might be influenced by extra uterine development. Specific
      EEG abnormalities are related to increased risk of neurological disorders.
      SIGNIFICANCE: Extra uterine development of very low birth weight delays the
      acquisition of maturational EEG patterns.

PMID- 24315810
TI  - Relative changes in ankle and hip control during bilateral joint movements in
      persons with multiple sclerosis.
AB  - OBJECTIVE: The purpose of this study was to quantify hip and ankle impairments
      contributing to movement dysfunction in multiple sclerosis (MS). METHODS:
      Volitional phasing of bilateral hip and ankle torques was assessed using a load
      cell-instrumented servomotor drive system in ten participants with MS and 10 age
      matched healthy participants. The hips and ankles were separately bilaterally
      oscillated 180 degrees  out of phase (40 degrees  range of motion) at a frequency
      of 0.75 Hz while the other joints were held stationary. Participants were
      instructed to assist in the same direction as the robot-imposed movement. The hip
      and ankle torques were measured and work was calculated for each movement.
      RESULTS: Total negative work at the ankle was significantly different between
      groups (p=0.040). The participants with MS produced larger negative work during
      hip flexion (p=0.042) and ankle flexion (p=0.037). Negative work at the hip was
      significantly correlated with the Berg Balance Scores and Timed 25 Feet Walk
      Test, and trends demonstrated increasing negative work with increasing clinical
      impairment in MS. CONCLUSIONS: These results suggest an increased importance of
      the hip in functional balance and gait in MS. SIGNIFICANCE: Rehabilitation
      strategies targeting ankle recovery or compensation using the hip might improve
      movement function in MS.

PMID- 24315812
TI  - Efficient catalysis of Suzuki-Miyaura C-C coupling reactions with palladium(II)
      complexes of partially hydrolyzed bisimine ligands: a process important in
      environment context.
AB  - Potentially hexadentante [O(-),N,E:E,N,O(-)] chalcogenated bisimine ligands L1-L3
      have been synthesized by reaction of 1,1'-(4,6-dihydroxy-1,3
      phenylene)bisethanone with H2N(CH2)2SPh, H2N(CH2)2SePh and H2N(CH2)2TeC6H4-4-OMe
      respectively. The L1-L3 react with Na2PdCl4 resulting in their partial
      hydrolysis, which appears to be metal-promoted. Of the two [(CH3)CN(CH2)2EAr]
      fragments of L1-L3, one is converted to (CH3)CO and H2N(CH2)2EAr eliminated. The
      hydrolysis products 1-[C(CH3)N(CH2)2SPh]-3-[C(CH3)O]-4,6-[OH]2C6H2 (L1'), 1
      [C(CH3)N(CH2)2SePh]-3-[C(CH3)O]-4,6-[OH]2C6H2 (L2') and 1-[C(CH3)N(CH2)2TeC6H4-4
      OMe]-3-[C(CH3)O]-4,6-[OH]2C6H2 (L3') have formed complexes [PdCl(L'-H)] (1, 3 and
      5). The other product of hydrolysis H2N(CH2)2EAr (L") reacted with Na2PdCl4
      yielding the complexes [PdL"Cl2] (2, 4 and 6). All the complexes (1-6) were found
      thermally and air stable. Complexes 1, 3 and 5 have been investigated as
      catalysts for Suzuki-Miyaura CC coupling reactions. The catalytic activities of 1
      and 3 which are palladium complexes of S- and Se-containing Schiff base
      derivatives respectively, were found good for the Suzuki-Miyaura cross-coupling
      of aryl bromides with phenylboronic acid under mild reaction conditions. The
      Pd(II) complex (3) of selenated ligand was found active to catalyze the coupling
      of 2-chlorobenzaldehyde and 3-chlorotoluene. The activity of Te analog was found
      to be the lowest one as it failed in catalyzing the coupling of electronically
      deactivated aryl bromides.

PMID- 24315813
TI  - Transient-state studies and neural modeling of the removal of a gas-phase
      pollutant mixture in a biotrickling filter.
AB  - The removal efficiency (RE) of gas-phase hydrogen sulfide (H), methanol (M) and
      alpha-pinene (P) in a biotrickling filter (BTF) was modeled using artificial
      neural networks (ANNs). The inlet concentrations of H, M, P, unit flow and
      operation time were used as the model inputs, while the outputs were the RE of H,
      M and P, respectively. After testing and validating the results, an optimal
      network topology of 5-8-3 was obtained. The model predictions were analyzed using
      Casual index (CI) values. M removal in the BTF was influenced positively by the
      inlet concentration of M in mixture (CI=3.79), while the removal of P and H were
      influenced more by the time of BTF operation (CI=25.36, 15.62). The BTF was
      subjected to different types of short-term shock-loads: 5-h shock-load of HMP
      mixture simultaneously, and 2.5-h shock-load of either H, M, or P, individually.
      It was observed that, short-term shock-loads of individual pollutants (M or H)
      did not significantly affect their own removal, but the removal of P was affected
      by 50%. The results from this study also show the sensitiveness of the well
      acclimated BTF to handle sudden load variations and also revival capability of
      the BTF when pre-shock conditions were restored. 

PMID- 24315814
TI  - Patterns of presence and concentration of pesticides in fish and waters of the
      Jucar River (Eastern Spain).
AB  - The Jucar River, in a typical Mediterranean Basin, is expected to suffer a
      decline in water quality and quantity as a consequence of the climate change.
      This study is focused on the presence and distribution of pesticides in water and
      fish, using the first extensive optimization and application of the QuEChERS
      method to determine pesticides in freshwater fish. Majority pesticides in water -
      in terms of presence and concentration - were dichlofenthion, chlorfenvinphos,
      imazalil, pyriproxyfen and prochloraz (associated with a frequent use in farming
      activities), as well as buprofezin, chlorpyriphos and hexythiazox. In fish, the
      main compounds were azinphos-ethyl, chlorpyriphos, diazinon, dimethoate and
      ethion. The analysis of bio-concentration in fish indicated differences by
      species. The maximum average concentration was detected in European eel (a
      critically endangered fish species). The wide presence of pesticides in water and
      fish suggests potential severe effects on fish populations and other biota in
      future scenarios of climate change, in a river basin with several endemic and
      endangered fish species. The potential effects of pesticides in combination with
      multiple stressors require further research to prioritize the management of
      specific chemicals and suggest effective restoration actions at the basin scale. 

PMID- 24315815
TI  - Sensorineural hearing loss amplifies neural coding of envelope information in the
      central auditory system of chinchillas.
AB  - People with sensorineural hearing loss often have substantial difficulty
      understanding speech under challenging listening conditions. Behavioral studies
      suggest that reduced sensitivity to the temporal structure of sound may be
      responsible, but underlying neurophysiological pathologies are incompletely
      understood. Here, we investigate the effects of noise-induced hearing loss on
      coding of envelope (ENV) structure in the central auditory system of anesthetized
      chinchillas. ENV coding was evaluated noninvasively using auditory evoked
      potentials recorded from the scalp surface in response to sinusoidally amplitude
      modulated tones with carrier frequencies of 1, 2, 4, and 8 kHz and a modulation
      frequency of 140 Hz. Stimuli were presented in quiet and in three levels of white
      background noise. The latency of scalp-recorded ENV responses was consistent with
      generation in the auditory midbrain. Hearing loss amplified neural coding of ENV
      at carrier frequencies of 2 kHz and above. This result may reflect enhanced ENV
      coding from the periphery and/or an increase in the gain of central auditory
      neurons. In contrast to expectations, hearing loss was not associated with a
      stronger adverse effect of increasing masker intensity on ENV coding. The
      exaggerated neural representation of ENV information shown here at the level of
      the auditory midbrain helps to explain previous findings of enhanced sensitivity
      to amplitude modulation in people with hearing loss under some conditions.
      Furthermore, amplified ENV coding may potentially contribute to speech perception
      problems in people with cochlear hearing loss by acting as a distraction from
      more salient acoustic cues, particularly in fluctuating backgrounds. 

PMID- 24315816
TI  - Effect of interleukin-17A and interleukin-17F gene polymorphisms on the risk of
      gastric cancer in a Chinese population.
AB  - We selected six tagged single-nucleotide polymorphisms (SNPs) in the IL-17A and
      IL-17F genes, and evaluated the relationship between the six common SNPs and H.
      pylori infection, tobacco smoking and subsites of gastric cancer in gastric
      cancer patients. Genotyping of IL-17A (rs2275913, rs3748067 and rs3819025) and IL
      17A (rs763780, rs9382084, and rs12203582) was performed in a 384-well plate
      format on the MassARRAY(r) platform. An unconditional multiple logistical
      regression model was performed to determine the association between IL-17A and IL
      17F genetic variations and gastric cancer risk. Unconditional logistic regression
      analysis showed that subjects carrying the rs2275913AA and rs3748067 TT genotypes
      were 1.70 and 3.45 times more likely to develop gastric cancer. Furthermore,
      rs2275913 and rs3748067 genetic variants significantly interacted with H. pylori
      infection on the risk of gastric cancer. The interaction between rs3748067 and
      rs9382084 genetic variants and tobacco smoking trend was significant. In
      addition, rs2275913, rs3748067 and rs9382084 genetic variants were only
      associated with non-cardia gastric cancer. The findings suggest that the
      rs2275913, rs3748067 and rs9382084 polymorphisms increase the risk of gastric
      cancer, and they interact with H. pylori infection, tobacco smoking and subsites
      of gastric cancer. These findings could be helpful in identifying individuals at
      increased risk for developing gastric cancer.

PMID- 24315817
TI  - Functional analysis of BpDREB2 gene involved in salt and drought response from a
      woody plant Broussonetia papyrifera.
AB  - The dehydration-responsive element binding proteins (DREBs) are important
      transcription factors in the regulation of plant responses to abiotic stresses.
      In this study, BpDREB2, an AP2/DREB-type transcription factor gene, was cloned
      from a woody plant, Broussonetia papyrifera by RACE-PCR. Sequence analyses
      revealed that BpDREB2 protein has three characteristic domains, including an
      AP2/EREBP, a nuclear localization signal and an acidic activation domain. Yeast
      one-hybrid assays showed that BpDREB2 protein specifically binds to the DRE
      sequence and activates the expression of reporter genes in yeast. These results
      suggested that BpDREB2 protein could function as a transcription factor of DREB
      family. The expression of BpDREB2 gene was remarkably induced by dehydration and
      high-salt treatments, but no significant change was observed under ABA or low
      temperature conditions. Importantly, transgenic expression of BpDREB2 gene in
      Arabidopsis significantly enhanced its tolerance to salt and freezing without
      causing growth retardation. Taken together, these results suggested that BpDREB2
      is a novel member of the AP2/EREBP trans-acting factor family which could enhance
      salt stress tolerance of plants and has the potential application in the
      improvement of crops and economical tree species.

PMID- 24315818
TI  - Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting
      PTEN and activating Wnt/beta-catenin signaling.
AB  - MicroRNAs (miRNAs) are strongly implicated in many cancers, including breast
      cancer. Recently, microRNA-301a (miR-301a) has been proved to play a substantial
      role in gastric cancer, but its functions in the context of breast cancer remain
      unknown. Here we report that miR-301a was markedly upregulated in primary tumor
      samples from patients with distant metastases and pro-metastatic breast cancer
      cell lines. Gain-of-function and loss-of-function studies showed that ectopic
      overexpression of miR-301a promoted breast cancer cell migration, invasion and
      metastasis both in vitro and in vivo. Notably, Wnt/beta-catenin signaling was
      hyperactivated in metastatic breast cancer cells that express miR-301a, and
      mediated miR-301a-induced invasion and metastasis. Furthermore, miR-301a directly
      targeted and suppressed PTEN, one negative regulator of the Wnt/beta-catenin
      signaling cascade. These results demonstrate that miR-301a maintains
      constitutively activated Wnt/beta-catenin signaling by directly targeting PTEN,
      which promotes breast cancer invasion and metastasis. Taken together, our
      findings reveal a new regulatory mechanism of miR-301a and suggest that miR-301a
      might be a potential target in breast cancer therapy.

PMID- 24315819
TI  - Infantile-onset ascending hereditary spastic paraplegia with bulbar involvement
      due to the novel ALS2 mutation c.2761C>T.
AB  - Recessive mutations in the alsin gene cause three clinically distinct motor
      neuron diseases: juvenile amyotrophic lateral sclerosis (ALS2), juvenile primary
      lateral sclerosis (JPLS) and infantile-onset ascending hereditary spastic
      paraplegia (IAHSP). A total of 23 different ALS2 mutations have been described
      for the three disorders so far. Most of these mutations result in a frameshift
      leading to a premature truncation of the alsin protein. We report the novel ALS2
      truncating mutation c.2761C>T; p.R921X detected by homozygosity mapping and
      sequencing in two infants affected by IAHSP with bulbar involvement. The mutation
      c.2761C>T resides in the pleckstrin domain, a characteristic segment of guanine
      nucleotide exchange factors of the Rho GTPase family, which is involved in the
      overall neuronal development or maintenance. This study highlights the importance
      of using homozygosity mapping combined with candidate gene analysis to identify
      the underlying genetic defect as in this Saudi consanguineous family.

PMID- 24315820
TI  - Interaction between TGF-beta1 (869C/T) polymorphism and biochemical risk factor
      for prediction of disease progression in rheumatoid arthritis.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease.
      Transforming growth factor-beta1 (TGF-beta1) may be a promising candidate gene
      for susceptibility and severity in RA. We aimed to determine whether TGF-beta1
      polymorphism is associated with susceptibility to RA and progression of joint
      destruction, as well as to identify the interaction between TGF-beta1
      polymorphism and biochemical risk factor. METHODS: A total of 160 RA patients and
      168 healthy unrelated controls were tested for the TGF-beta1 (869C/T)
      polymorphism using polymerase chain reaction. RESULTS: The TGF-beta1 T allele was
      associated with susceptibility to RA. Within the RA group, TGF-beta1 T allele
      carriers had a significant increased risk to develop osteoporosis (OR=4.4, 95%
      CI=-2. 4-8.1, P<0.001), as well as more likely to develop bone erosion (OR=1.7,
      95% CI=0. 99-2.7, P=0. 034). Better prediction was achieved when the TGF-beta1 TT
      genotype was used in combination with either elevated, rheumatoid factor (RF) or
      C-reactive protein (CRP) (OR=6.8, 3.7 respectively). Also, they increased the
      risk to develop bone erosion in patients with rheumatoid arthritis (OR=3.3, 9.8,
      P=0.017, 0.001 respectively). CONCLUSION: Our results suggest that TGF-beta1 TT
      genotype may determine the development of osteoporosis and bone erosion in RA.
      Also, our results points to a synergism between TGF-beta1 TT genotype and
      elevated serum RF or elevated CRP that lead to the development of osteoporosis
      and bone erosion in patients with rheumatoid arthritis.

PMID- 24315821
TI  - Profiling microRNAs and their targets in an important fleshy fruit: tomato
      (Solanum lycopersicum).
AB  - Tomato (Solanum lycopersicum) is an important and the most useful plant based
      diet. It is widely used for its antioxidant property. Presently, only two digits,
      tomato microRNAs (miRNAs) are reported in miRBase: a miRNA database. This study
      is aimed to profile and characterize more miRNAs and their targets in tomato. A
      comprehensive comparative genomic approach is applied and a total of 109 new
      miRNAs belonging to 106 families are identified and characterized from the tomato
      expressed sequence tags (ESTs). All these potential miRNAs are profiled for the
      first time in tomato. The profiled miRNAs are also observed with stable stem-loop
      structures (Precursor-miRNAs), whose length ranges from 45 to 329 nucleotides
      (nt) with an average of 125 nt. The mature miRNAs are found in the stem of pre
      miRNAs and their length ranges from 19 to 24 nt with an average of 21 nt.
      Furthermore, twelve miRNAs are randomly selected and experimentally validated
      through RT-PCR. A total of 406 putative targets are also predicted for the newly
      109 tomato miRNAs. These targets are involved in structural protein, metabolism,
      transcription factor, growth & development, stress related, signaling pathways,
      storage proteins and other vital processes. Some important proteins like; 9
      cisepoxycarotenoid dioxygenase (NCED), transcription factor MYB, ATP-binding
      cassette transporters, terpen synthase, 14-3-3 and TIR-NBS proteins are also
      predicted as putative targets for tomato miRNAs. These findings improve a
      baseline data of miRNAs and their targets in tomato. This baseline data can be
      utilized to fine tune this important fleshy fruit for nutritional & antioxidant
      properties and also under biotic & abiotic stresses.

PMID- 24315823
TI  - Identification and characterization of salt responsive miRNA-SSR markers in rice
      (Oryza sativa).
AB  - Salinity is an important abiotic stress that affects agricultural production and
      productivity. It is a complex trait that is regulated by different molecular
      mechanisms. miRNAs are non-coding RNAs which are highly conserved and regulate
      gene expression. Simple sequence repeats (SSRs) are robust molecular markers for
      studying genetic diversity. Although several SSR markers are available now,
      challenge remains to identify the trait-specific SSRs which can be used for
      marker assisted breeding. In order to understand the genetic diversity of salt
      responsive-miRNA genes in rice, SSR markers were mined from 130 members of salt
      responsive miRNA genes of rice and validated among the contrasting panels of
      tolerant as well as susceptible rice genotypes, each with 12 genotypes. Although
      12 miR-SSRs were found to be polymorphic, only miR172b-SSR was able to
      differentiate the tolerant and susceptible genotypes in 2 different groups. It
      had also been found that miRNA genes were more diverse in susceptible genotypes
      than the tolerant one (as indicated by polymorphic index content) which might
      interfere to form the stem-loop structure of premature miRNA and their subsequent
      synthesis in susceptible genotypes. Thus, we concluded that length variations of
      the repeats in salt responsive miRNA genes may be responsible for a possible
      sensitivity to salinity adaptation. This is the first report of characterization
      of trait specific miRNA derived SSRs in plants. 

PMID- 24315822
TI  - Sp1 and Sp3 transcription factors regulate the basal expression of human
      microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far
      upstream promoter.
AB  - Microsomal epoxide hydrolase (mEH, EPHX1) is a critical biotransformation enzyme,
      catalyzing the metabolism of many xenobiotics. Human mEH is transcribed using
      alternative promoters. The upstream E1 promoter is active in liver while the far
      upstream E1b promoter drives the expression of mEH in all tissues, including
      liver. Although several liver-specific transcription factors have been identified
      in the regulation of E1 transcription, little is known regarding the mechanisms
      of E1b transcriptional regulation. Genome-wide mapping of DNase I hypersensitive
      sites revealed an open chromatin region between nucleotide -300 upstream and +400
      downstream of E1b. This area coincides with a previously described promoter
      region responsible for maintaining high basal promoter activity. In silico
      analysis of this location revealed several Sp1/Sp3 binding sites. Site-directed
      mutagenesis of these motifs suppressed the transactivation activity of the E1b
      proximal promoter, indicating their importance as contributors to E1b promoter
      regulation. Further, E1b promoter activities were increased significantly
      following Sp1 and Sp3 overexpression, while Mithramycin A, a selective Sp1
      inhibitor, reduced the promoter activities. EMSA studies demonstrated that Sp1
      bound to two putative Sp1/Sp3 binding sites. ChIP analysis confirmed that both
      endogenous Sp1 and Sp3 were bound to the proximal promoter region of E1b.
      Knockdown of Sp1 expression using siRNA did not alter the endogenous E1b
      transcriptional level, while knockdown of Sp3 greatly decreased E1b expression in
      different human cell lines. Taken together, these results support the concept
      that Sp1 and Sp3 are functionally involved as transcriptional integrators
      regulating the basal expression of the derived mEH E1b variant transcript. 

PMID- 24315824
TI  - Microduplications in 22q11.2 and 8q22.1 associated with mild mental retardation
      and generalized overgrowth.
AB  - The 22q11.2 microduplication is a genomic disorder, characterized from a variable
      phenotype ranging from different defects to normality. The most common
      microduplication of 22q11.2 is 3 Mb in size, but there are also cases reported
      with atypical duplications between 0.8 Mb and 6Mb. Here, we describe a case of a
      child with macrocephaly, overgrowth with advanced bone age, attention deficits,
      evidence of mild mental retardation and dysmorphic features. An array-CGH
      analysis detected a 252 Kb duplication at the 22q11.2 region inherited from
      mother and 142 Kb duplication at 8q22.1 region inherited from father. Both
      parents show mild dysmorphic features. The duplicated genes in chromosomes 22q
      and 8q are TOP3B and PGCP, respectively. We describe for the first time a patient
      carrying the smaller atypical 22q11.2 duplication who also presents with mild
      mental retardation and generalized overgrowth. This patient has an additional
      duplication in 8q22.1 which may act as a genomic modifier of its clinical
      phenotype.

PMID- 24315825
TI  - Micromolar changes in lysophosphatidylcholine concentration cause minor effects
      on mitochondrial permeability but major alterations in function.
AB  - Mice deficient in group 1b phospholipase A2 have decreased plasma
      lysophosphatidylcholine and increased hepatic oxidation that is inhibited by
      intraperitoneal lysophosphatidylcholine injection. This study sought to identify
      a mechanism for lysophosphatidylcholine-mediated inhibition of hepatic oxidative
      function. Results showed that in vitro incubation of isolated mitochondria with
      40-200MUM lysophosphatidylcholine caused cyclosporine A-resistant swelling in a
      concentration-dependent manner. However, when mitochondria were challenged with
      220MUM CaCl2, cyclosporine A protected against permeability transition induced by
      40MUM, but not 80MUM lysophosphatidylcholine. Incubation with 40-120MUM
      lysophosphatidylcholine also increased mitochondrial permeability to 75MUM CaCl2
      in a concentration-dependent manner. Interestingly, despite incubation with 80MUM
      lysophosphatidylcholine, the mitochondrial membrane potential was steady in the
      presence of succinate, and oxidation rates and respiratory control indices were
      similar to controls in the presence of succinate, glutamate/malate, and palmitoyl
      carnitine. However, mitochondrial oxidation rates were inhibited by 30-50% at
      100MUM lysophosphatidylcholine. Finally, while 40MUM lysophosphatidylcholine has
      no effect on fatty acid oxidation and mitochondria remained impermeable in intact
      hepatocytes, 100MUM lysophosphatidylcholine inhibited fatty acid stimulated
      oxidation and caused intracellular mitochondrial permeability. Taken together,
      these present data demonstrated that LPC concentration dependently modulates
      mitochondrial microenvironment, with low micromolar concentrations of
      lysophosphatidylcholine sufficient to change hepatic oxidation rate whereas
      higher concentrations are required to disrupt mitochondrial integrity. 

PMID- 24315826
TI  - MAPK signaling is required for dedifferentiation of acinar cells and development
      of pancreatic intraepithelial neoplasia in mice.
AB  - BACKGROUND & AIMS: Kras signaling via mitogen-activated protein kinase (MAPK) is
      highly up-regulated in pancreatic cancer cells. We investigated whether MAPK
      signaling is required for the initiation and maintenance of pancreatic
      carcinogenesis in mice. METHODS: We studied the formation and maintenance of
      pancreatic intraepithelial neoplasia (PanINs) in p48Cre; TetO-KrasG12D;
      Rosa26(rtTa-IRES-EGFP) (iKras*) mice and LSL-KrasG12D mice bred with p48Cre mice
      (KC). Mice were given oral PD325901, a small-molecule inhibitor of MEK1 and MEK2
      (factors in the MAPK signaling pathway), along with injections of cerulein to
      induce pancreatitis. Other mice were given PD325901 only after PanINs developed.
      Pancreatic tissues were collected and evaluated using histologic,
      immunohistochemical, immunofluorescence, and electron microscopy analyses. Acinar
      cells were isolated from the tissues and the effects of MEK1 and 2 inhibitors
      were assessed. RESULTS: PD325901 prevented PanIN formation, but not pancreatitis,
      in iKras* and KC mice. In iKras* or KC mice given PD325901 at 5 weeks after
      PanINs developed, PanINs regressed and acinar tissue regenerated. The regression
      occurred through differentiation of the PanIN cells to acini, accompanied by re
      expression of the acinar transcription factor Mist1. CONCLUSIONS: In iKras* and
      KC mice, MAPK signaling is required for the initiation and maintenance of
      pancreatic cancer precursor lesions. MAPK signaling promotes formation of PanINs
      by enabling dedifferentiation of acinar cells into duct-like cells that are
      susceptible to transformation.

PMID- 24315828
TI  - Statin use is associated with reduced risk of histologic subtypes of esophageal
      cancer: a nested case-control analysis.
AB  - BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) or squamous
      cell cancer (ESCC) present with advanced, incurable disease. Statins have
      reported anti-carcinogenic effects and may be chemoprotective. We investigated
      the association between regular use of statins and the main histologic subtypes
      of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and
      ESCC) in the UK general population. METHODS: We identified all individuals in the
      UK General Practice Research Database diagnosed with esophageal cancer from 2000
      through 2009. Patients were linked to the National Cancer Registry to confirm
      histologic subtypes. Each patient was matched with up to 4 controls for age, sex,
      and practice. We performed a nested case-control analysis using conditional
      logistic regression to estimate the risk of each subtype with regular statin use,
      adjusted for body mass index, smoking, alcohol intake, and concomitant use of
      medications. RESULTS: In total, 581 participants with EAC, 213 with
      esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to
      2167, 783, and 1242 controls, respectively. Regular statin use was inversely
      associated with development of EAC (odds ratio = 0.58; 95% confidence interval:
      0.39-0.87) (with significant dose and duration responses) and esophagogastric
      junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92)
      (with high-dose use only). Statin use for 1-4 years was inversely associated with
      ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98). CONCLUSIONS: In a
      nested case-control analysis of a UK population-based cohort, statin use was
      inversely associated with histologic subtypes of esophageal cancer. Randomized
      controlled trials are warranted to determine whether statins have chemopreventive
      effects in high-risk groups.

PMID- 24315829
TI  - Landau-Kleffner syndrome: a study of 29 patients.
AB  - PURPOSE: The aim of the study was to retrospectively analyze the electroclinical
      features, etiology, treatment, and prognosis of 29 patients with Landau-Kleffner
      syndrome (LKS) with a long-term follow-up. METHODS: Inclusion criteria were a
      diagnosis of LKS with: (1) acquired aphasia or verbal auditory aphasia; (2) with
      or without focal seizures, secondarily generalized tonic-clonic seizures,
      absences, or atonic seizures. RESULTS: Mean follow-up was 12 years. All cases
      except six had seizures. Before the onset of aphasia, developmental language and
      behavioral disturbances were present in 19 and 14 patients, respectively. All
      patients had verbal auditory agnosia. Aphasia was severe in 24 patients and
      moderate in five. Nonlinguistic cognitive dysfunctions were moderate in 14
      patients. Behavioral disturbances were found in 16 patients. During the
      continuous spike-and-wave discharges during slow sleep phase, the spike-wave
      index was >85% in 15, 50-85% in eight, and 30-50% in four. In two patients, the
      EEG recording showed occasional bilateral spikes, without continuous spike-and
      wave discharges during slow sleep. In this phase, the awake EEG recording showed
      more frequent interictal abnormalities, predominantly in the temporal regions.
      Eight patients recovered language completely, but the remaining patients continue
      to have language deficits of different degrees. CONCLUSION: Landau-Kleffner
      syndrome is an epileptic encephalopathy characterized by acquired verbal auditory
      aphasia and seizures in most of the patients associated with continuous or almost
      continuous spike-and-wave discharges during slow wave sleep. The most commonly
      used treatments were clobazam, ethosuximide, sulthiame. High-dose steroids were
      also administered. Adequate and early management may avoid language and cognitive
      deterioration.

PMID- 24315830
TI  - Filiform polyposis: A benign entity? Case report and literature review.
AB  - Filiform polyposis (FP) is a distinctive and unusual form of benign non syndromic
      polyposis that is occasionally encountered in the colon of patients with
      inflammatory bowel disease (IBD) history. FP is characterized by one to hundreds,
      slender, arborizing, vermiform projections in the colon lined by normal or
      inflammatory colonic mucosa. Only rare cases without history or evidence of IBD
      have been reported. In those cases, the sigmoid colon was the most common
      location and none of them showed dysplasia or malignancy neither at first
      evaluation nor during follow-up. In this report, we present the first case of FP
      associated with six adenomas developed on filiform polyps and invasive
      adenocarcinoma in the right colon of a 54 year-old man without a past medical
      history of IBD. 

PMID- 24315827
TI  - Mechanisms of obesity-induced gastrointestinal neoplasia.
AB  - Obesity is among the fastest growing diseases worldwide; treatment is inadequate,
      and associated disorders, including gastrointestinal cancers, have high morbidity
      and mortality. An increased understanding of the mechanisms of obesity-induced
      carcinogenesis is required to develop methods to prevent or treat these cancers.
      In this report, we review the mechanisms of obesity-associated colorectal,
      esophageal, gastric, and pancreatic cancers and potential treatment strategies. 

PMID- 24315832
TI  - Spatial memory extinction: a c-Fos protein mapping study.
AB  - While the neuronal basis of spatial memory consolidation has been thoroughly
      studied, the substrates mediating the process of extinction remain largely
      unknown. This study aimed to evaluate the functional contribution of selected
      brain regions during the extinction of a previously acquired spatial memory task
      in the Morris water maze. For that purpose, we used adult male Wistar rats
      trained in a spatial reference memory task. Learning-related changes in c-Fos
      inmunoreactive cells after training were evaluated in cortical and subcortical
      regions. Results show that removal of the hidden platform in the water maze
      induced extinction of the previously reinforced escape behavior after 16 trials,
      without spontaneous recovery 24h later. Extinction was related with significantly
      higher numbers of c-Fos positive nuclei in amygdala nuclei and prefrontal cortex.
      On the other hand, the lateral mammillary bodies showed higher number of c-Fos
      positive cells than the control group. Therefore, in contrast with the results
      obtained in studies of classical conditioning, we show the involvement of
      diencephalic structures mediating this kind of learning. In summary, our findings
      suggest that medial prefrontal cortex, the amygdala complex and diencephalic
      structures like the lateral mammillary nuclei are relevant for the extinction of
      spatial memory. 

PMID- 24315831
TI  - Central effects of ethanol interact with endogenous mu-opioid activity to control
      isolation-induced analgesia in maternally separated infant rats.
AB  - Endogenous opioid activity plays an important role in ethanol consumption and
      reinforcement in infant rats. Opioid systems are also involved in mediation and
      regulation of stress responses. Social isolation is a stressful experience for
      preweanling rats and changes the effects of ethanol through opioid-dependent
      mechanisms. The present study assessed effects of intracisternal (i.c.)
      administration of a selective mu-opioid antagonist (CTOP) and i.p. administration
      of a nonspecific opioid antagonist (naloxone) on voluntary intake and behavior in
      socially isolated 12-day-old (P12) pups treated with 0.5 g/kg ethanol. Voluntary
      intake of 0.1% saccharin or water, locomotion, rearing activity, paw licking and
      grooming were assessed during short-term isolation from littermates (STSI; 8-min
      duration). Thermal nociceptive reactivity was measured before and after this
      intake test, with normalized differences between pre- and post-test latencies of
      paw withdrawal from a hot plate (49 degrees C) used as an index of isolation
      induced analgesia (IIA). Results indicated several effects of social isolation
      and ethanol mediated through the mu-opioid system. Effects of low dose ethanol
      (0.5 g/kg) and voluntary consumption of saccharin interacted with endogenous mu
      opioid activity associated with STSI. Blockade of mu-opioid receptors on
      saccharin consumption and paw licking-grooming affected intoxicated animals. Low
      dose ethanol and ingestion of saccharin blunted effects of CTOP on rearing
      behavior and nociceptive reactivity. Central injections of CTOP stimulated paw
      licking and grooming dependent on ethanol dose and type of fluid ingested.
      Ethanol selectively increased saccharin intake during STSI in females, naloxone
      and CTOP blocked ethanol-mediated enhancement of saccharin intake. We suggest
      that enhancement of saccharin intake by ethanol during STSI is the product of
      synergism between isolation-induced mu-opioid activity that increases the pup's
      sensitivity to appetitive taste stimulation and the anxiolytic effects of 0.5
      g/kg ethanol that decreases behaviors otherwise competing with independent
      ingestive activity.

PMID- 24315833
TI  - Novel behavioural characteristics of female APPSwe/PS1DeltaE9 double transgenic
      mice.
AB  - Murine models are commonly used to evaluate progression of Alzheimer's disease.
      APPSwe/PS1DeltaE9 (APPxPS1) mice have previously been reported to demonstrate
      impaired learning and memory in the Morris water maze test. However, this
      paradigm introduces a variety of behaviours that may confound performance of the
      mice, thus an alternative was sought. A battery of behavioural tests (light-dark
      test, elevated plus maze, novel object recognition task, social recognition test,
      cheeseboard task and prepulse inhibition) was used to investigate various
      behavioural and cognitive domains with relevance to Alzheimer's disease. We found
      9-month old female APPxPS1 mice exhibited impaired spatial memory in the reversal
      cheeseboard task. In addition, task-dependent hyperlocomotion and anxiolytic-like
      behaviours were observed in the light-dark test. Female APPxPS1 demonstrated
      intact object recognition memory and sensorimotor gating was not significantly
      decreased compared to control mice except for one particular interstimulus
      interval. The social recognition test failed to detect preference for social
      novelty in control females. In conclusion, this is the first study to describe a
      memory deficit in female APPxPS1 mice in the hidden cheeseboard task. Transgenic
      females also exhibited task-dependent reduction in anxiety behaviours and
      hyperlocomotion. These novel findings enhance our understanding of the
      behavioural phenotype of APPxPS1 females and present the cheeseboard as a valid
      alternative to other established spatial memory tests. Furthermore, the task
      dependency of some of our findings suggests that behavioural profiling of APPxPS1
      transgenic mice should be assessed using a variety of behavioural paradigms.

PMID- 24315834
TI  - Altered NMDA receptor subunit gene expression in brains of mice showing high vs.
      low sensitization to ethanol.
AB  - Repeated administration of ethanol (EtOH) in mice leads to behavioural
      sensitization, a progressive increase in locomotor activity. Since not all mice
      sensitize equally to EtOH, the objective of the present study was to determine
      whether variability in this response is associated with altered subunit gene
      expression of the N-methyl-d-aspartate receptor (NMDAR), a primary target of
      EtOH. We examined NR1, NR2A, and NR2B expression throughout the brain during the
      development phase of EtOH sensitization, as well as after a 14 day withdrawal
      period. Male DBA/2J mice received 5-6 injections of EtOH (2.2g/kg, i.p.) or
      saline (SAL) and were categorized as high- (HS) or low-sensitized (LS) on the
      basis of locomotor activity scores after the final injection. NMDAR subunits were
      analyzed by in situ hybridization in brains removed either immediately following
      the final EtOH injection or 14 days thereafter. At the end of development phase,
      LS mice showed increased NR2A expression in several brain areas compared to
      saline controls. LS animals also had greater NR1 expression in the nucleus
      accumbens core (+11%, p=0.05) and shell (+14%, p=0.04) compared to HS mice, and
      increased NR2B expression in hippocampal CA1 (+20%, p=0.05) relative to saline
      treated animals. High-sensitized mice showed increased NR2A expression in the bed
      nucleus of the stria terminalis when compared to controls (+54%, p=0.02). No
      differences in gene expression between the treatment groups were seen 14 days
      after the final injection. These findings suggest that region-specific NMDAR
      subunits may play an important role in the variability associated with the
      induction of EtOH sensitization. Low-sensitized mice may be more sensitive to the
      NMDAR inhibitory effects of EtOH, with the NR1 and NR2A subunits potentially
      playing a key role in the failure to sensitize upon repeated EtOH exposure. 

PMID- 24315835
TI  - 3D models of human ERalpha and ERbeta complexed with coumestrol.
AB  - Coumestrol, a phytoestrogen found in alfalfa, clover, and beans, has nM affinity
      for both estrogen receptor-alpha [ERalpha] and ERbeta. Recently, a novel activity
      of coumestrol was reported: coumestrol binding to human ERbeta represses
      microglia-mediated inflammation, which is associated with various
      neurodegenerative diseases, such as multiple sclerosis. In contrast, estradiol
      binding to ERbeta had little or no effect on repression of microglia-mediated
      inflammation. Coumestrol and estradiol have several structural differences, which
      suggest that each ligand could induce different conformations in ERbeta and,
      thus, different transcriptional responses in brain microglia. To begin to
      understand how coumestrol binds to ERbeta and ERalpha, we constructed 3D models
      of coumestrol with human ERbeta and ERalpha, which were compared to the
      structures of these ERs with estradiol. Of four possible orientations of
      coumestrol in ERalpha and ERbeta, one orientation had the most favorable contacts
      with both ERs. Other phytochemicals may activate ERbeta and inhibit inflammation
      in brain microglia and be useful therapeutics for inflammatory conditions in the
      brain. 

PMID- 24315836
TI  - Structural insights into Estrogen Related Receptor-beta modulation: 4
      methylenesterols from Theonella swinhoei sponge as the first example of marine
      natural antagonists.
AB  - In this paper, we report the first evidence of 4-methylenesterols, isolated from
      the marine sponge Theonella swinhoei, as antagonists of Estrogen Related
      Receptors (ERRs). The interactions of 4-methylenesterols with ERRs were
      investigated through a multi-parametric approach involving biological assays and
      molecular modelling. Here the first homology model of active and inactive
      conformations of the Estrogen Related Receptor beta (ERRbeta) is also reported,
      benchmarked with the well known agonists gsk4716 and genistein, and the
      antagonists 4-hydroxytamoxifen and diethylstilbestrol. Our proposed model could
      contribute to the clarification of small molecule interaction mode in the ERRbeta
      and, notably, to the rational design of new potential and selective modulators of
      this emerging therapeutic target. 

PMID- 24315837
TI  - Developing zebrafish models of autism spectrum disorder (ASD).
AB  - Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder with
      complex symptoms and unclear, multi-factorial pathogenesis. Animal (rodent)
      models of ASD-like behavior are extensively used to study genetics, circuitry and
      molecular mechanisms of ASD. The evolutionarily conserved nature of social
      behavior and its molecular pathways suggests that alternative experimental models
      can be developed to complement and enhance the existing rodent ASD paradigms. The
      zebrafish (Danio rerio) is rapidly becoming a popular model organism in
      neuroscience and biological psychiatry to study brain function, model human brain
      disorders and explore their genetic or pharmacological modulation. Representing
      highly social animals, zebrafish emerge as a strong potential model organism to
      study normal and pathological social phenotypes, as well as several other ASD
      like symptoms. Here, we discuss the developing utility of zebrafish in modeling
      ASD as a new emerging field in translational neuroscience and drug discovery. 

PMID- 24315838
TI  - Dissociable roles of default-mode regions during episodic encoding.
AB  - We investigated the role of distinct regions of the default-mode network (DMN)
      during memory encoding with fMRI. Subjects encoded words using either a strategy
      that emphasized self-referential (pleasantness) processing, or one that
      emphasized semantic (man-made/natural) processing. During encoding subjects were
      intermittently presented with thought probes to evaluate if they were
      concentrated and on-task or exhibiting task-unrelated thoughts (TUT). After the
      scanning session subjects performed a source retrieval task to determine which of
      two judgments they performed for each word at encoding. Source retrieval accuracy
      was higher for words encoded with the pleasantness vs. the man-made/natural task
      and there was a trend for higher performance for words preceding on-task vs. TUT
      reports. fMRI results show that left anterior medial PFC and left angular gyrus
      activity was greater during successful vs. unsuccessful encoding during both
      encoding tasks. Greater activity in left anterior cingulate and bilateral lateral
      temporal cortex was related successful vs. unsuccessful encoding only in the
      pleasantness task. In contrast, posterior cingulate, right anterior cingulate and
      right temporoparietal junction were activated to a greater extent in unsuccessful
      vs. successful encoding across tasks. Finally, activation in posterior cingulate
      and bilateral dorsolateral prefrontal cortex was related to TUT across tasks;
      moreover, we observed a conjunction in posterior cingulate between encoding
      failure and TUT. We conclude that DMN regions play dissociable roles during
      memory formation, and that their association with subsequent memory may depend on
      the manner in which information is encoded and retrieved. 

PMID- 24315839
TI  - Temporal and spectral profiles of stimulus-stimulus and stimulus-response
      conflict processing.
AB  - The ability to detect and resolve conflict is an essential function of cognitive
      control. Laboratory studies often use stimulus-response-compatibility (SRC) tasks
      to examine conflict processing in order to elucidate the mechanism and modular
      organization of cognitive control. Inspired by two influential theories regarding
      cognitive control, the conflict monitoring theory (Botvinick, Braver, Barch,
      Carter, & Cohen, 2001) and dimensional overlap taxonomy (Kornblum, Hasbroucq, &
      Osman, 1990), we explored the temporal and spectral similarities and differences
      between processing of stimulus-stimulus (S-S) and stimulus-response (S-R)
      conflicts with event related potential (ERP) and time-frequency measures. We
      predicted that processing of S-S conflict starts earlier than that of S-R
      conflict and that the two types of conflict may involve different frequency
      bands. Participants were asked to perform two parallel SRC tasks, both combining
      the Stroop task (involving S-S conflict) and Simon task (involving S-R conflict).
      ERP results showed pronounced SRC effects (incongruent vs. congruent) on N2 and
      P3 components for both S-S and S-R conflicts. In both tasks, SRC effects of S-S
      conflict took place earlier than those of S-R conflict. Time-frequency analysis
      revealed that both types of SRC effects modulated theta and alpha bands, while S
      R conflict effects additionally modulated power in the beta band. These results
      indicated that although S-S and S-R conflict processing shared considerable ERP
      and time-frequency properties, they differed in temporal and spectral dynamics.
      We suggest that the modular organization of cognitive control should take both
      commonality and distinction of S-S and S-R conflict processing into
      consideration. 

PMID- 24315841
TI  - Preterm birth affects the developmental synergy between cortical folding and
      cortical connectivity observed on multimodal MRI.
AB  - The survival rates of infants born prematurely have improved as a result of
      advances in neonatal care, although there remains an increased risk of subsequent
      disability. Accurate measurement of the shape and appearance of the very preterm
      brain at term-equivalent age may guide the development of predictive biomarkers
      of neurological outcome. We demonstrate in 92 preterm infants (born at an average
      gestational age of 27.0+/-2.7weeks) scanned at term equivalent age (scanned at
      40.4+/-1.74weeks) that the cortical sulcation ratio varies spatially over the
      cortical surface at term equivalent age and correlates significantly with
      gestational age at birth (r=0.49,p<0.0001). In the underlying white matter,
      fractional anisotropy of local white matter regions correlated significantly with
      gestational age at birth at term equivalent age (for the genu of the corpus
      callosum r=0.26,p=0.02 and for the splenium r=0.52,p<0.001) and in addition the
      fractional anisotropy in these local regions varies according to location.
      Finally, we demonstrate that connectivity measurements from tractography
      correlate significantly and specifically with the sulcation ratio of the
      overlying cortical surface at term equivalent age in a subgroup of 20 infants
      (r={0.67,0.61,0.86}, p={0.004,0.01,0.00002}) for tract systems emanating from the
      left and right corticospinal tracts and the corpus callosum respectively).
      Combined, these results suggest a close relationship between the cortical surface
      phenotype and underlying white matter structure assessed by diffusion weighted
      MRI. The spatial surface pattern may allow inference on the connectivity and
      developmental trajectory of the underlying white matter complementary to
      diffusion imaging and this result may guide the development of biomarkers of
      functional outcome. 

PMID- 24315840
TI  - FMRI of phonemic perception and its relationship to reading development in
      elementary- to middle-school-age children.
AB  - Neuroimaging studies suggest that categorical perception of speech phonemes in
      adults is primarily subserved by a pathway from bilateral primary auditory areas
      to association areas in the left middle superior temporal cortex, but the neural
      substrates underlying categorical speech perception in children are not yet
      known. Here, fMRI was used to examine the neural substrates associated with
      phoneme perception in 7- to 12-year-old children as well as the relationships
      among level of expertise in phoneme perception, the associated activation, and
      the development of reading and phonological processing abilities. While multiple
      regions in left frontal, temporal, and parietal cortex were found to be more
      responsive to phonemic than nonphonemic sounds, the extent of left lateralization
      in posterior temporal and parietal regions during phonemic relative to
      nonphonemic discrimination differed depending on the degree of categorical
      phoneme perception. In addition, an unexpected finding was that proficiency in
      categorical perception was strongly related to activation in the left ventral
      occipitotemporal cortex, an area frequently associated with orthographic
      processing. Furthermore, in children who showed lower proficiency in categorical
      perception, the level of categorical perception was positively correlated with
      reading ability and reading and reading-related abilities were inversely
      correlated with right mid-temporal activation in the phonemic relative to
      nonphonemic perception contrast. These results suggest that greater
      specialization of left hemisphere temporal and parietal regions for the
      categorical perception of phonemes, as well as activation of the region termed
      the visual word form area, may be important for the optimal developmental
      refinement of both phoneme perception and reading ability. 

PMID- 24315842
TI  - Fludarabine and exposure-targeted busulfan compares favorably with
      busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell
      transplantation: maintaining efficacy with less toxicity.
AB  - Busulfan (Bu) is used as a myeloablative agent in conditioning regimens before
      allogeneic hematopoietic cell transplantation (allo-HCT). In line with strategies
      explored in adults, patient outcomes may be optimized by replacing
      cyclophosphamide (Cy) with or without melphalan (Mel) with fludarabine (Flu). We
      compared outcomes in 2 consecutive cohorts of HCT recipients with a nonmalignant
      HCT indication, a myeloid malignancy, or a lymphoid malignancy with a
      contraindication for total body irradiation (TBI). Between 2009 and 2012, 64
      children received Flu + Bu at a target dose of 80-95 mg.h/L, and between 2005 and
      2008, 50 children received Bu targeted to 74-80 mg.h/L + Cy. In the latter group,
      Mel was added for patients with myeloid malignancy (n = 12). Possible confounding
      effects of calendar time were studied in 69 patients receiving a myeloablative
      dose of TBI between 2005 and 2012. Estimated 2-year survival and event-free
      survival were 82% and 78%, respectively, in the FluBu arm and 78% and 72%,
      respectively, in the BuCy (Mel) arm (P = not significant). Compared with the BuCy
      (Mel) arm, less toxicity was noted in the FluBu arm, with lower rates of acute
      (noninfectious) lung injury (16% versus 36%; P = .007), veno-occlusive disease
      (3% versus 28%; P = .003), chronic graft-versus-host disease (9% versus 26%; P =
      .047), adenovirus infection (3% versus 32%; P = .001), and human herpesvirus 6
      infection reactivation (21% versus 44%; P = .005). Furthermore, the median
      duration of neutropenia was shorter in the FluBu arm (11 days versus 22 days; P <
      .001), and the patients in this arm required fewer transfusions. Our data
      indicate that Flu (160 mg/m(2)) with targeted myeloablative Bu (90 mg.h/L) is
      less toxic than and equally effective as BuCy (Mel) in patients with similar
      indications for allo-HCT.

PMID- 24315844
TI  - Immune reconstitution after haploidentical hematopoietic stem cell
      transplantation.
AB  - Haploidentical hematopoietic stem cell transplantation (HSCT) offers the benefits
      of rapid and nearly universal donor availability and has been accepted worldwide
      as an alternative treatment for patients with hematologic malignancies who do not
      have a completely HLA-matched sibling or who require urgent transplantation.
      Unfortunately, serious infections and leukemia relapse resulting from slow immune
      reconstitution remain the 2 most frequent causes of mortality in patients
      undergoing haploidentical HSCT, particularly in those receiving extensively T
      cell-depleted megadose CD34(+) allografts. This review summarizes advances in
      immune recovery after haploidentical HSCT, focusing on the immune subsets likely
      to have the greatest impact on clinical outcomes. The progress made in
      accelerating immune reconstitution using different strategies after
      haploidentical HSCT is also discussed. It is our belief that a predictive immune
      subset-guided strategy to improve immune recovery might represent a future
      clinical direction. 

PMID- 24315843
TI  - A phase II study of a nonmyeloablative allogeneic stem cell transplant with
      peritransplant rituximab in patients with B cell lymphoid malignancies: favorably
      durable event-free survival in chemosensitive patients.
AB  - The aim of this prospective phase II trial was to determine the safety and
      efficacy of a nonmyeloablative conditioning program incorporating peritransplant
      rituximab in patients with CD20+ B cell non-Hodgkin lymphoma (B-NHL) receiving an
      allogeneic stem cell transplant (allo-SCT). Fifty-one adult B-NHL patients, with
      a median age of 54 years, were treated with cyclophosphamide, fludarabine, and
      200 cGy of total body irradiation. Rituximab 375 mg/m(2) was given on day -8 and
      in 4 weekly doses beginning day +21. Equine antithymocyte globulin was given to
      recipients of volunteer unrelated donor grafts. Graft-versus-host disease (GVHD)
      prophylaxis consisted of cyclosporine and mycophenolate mofetil and tacrolimus,
      sirolimus, and methotrexate in 8 and 43 patients, respectively. Thirty-three
      patients received grafts from unrelated donors, and 18 received grafts from
      matched related donors. All patients engrafted. Full donor chimerism in bone
      marrow and peripheral T cells was seen in 92% and 89% of patients, respectively,
      at 3 months after allo-SCT. The cumulative incidence of grades II to IV acute
      GVHD at 6 months was 25% (95% confidence interval [CI], 13% to 38%) and grades
      III to IV was 11% (95% CI, 2% to 20%). The 2-year cumulative incidence of chronic
      GVHD was 29% (95% CI, 15% to 44%). The 2-year event-free and overall survival for
      all patients was 72% (95% CI, 59% to 85%) and 78% (95% CI, 66% to 90%),
      respectively. The 2-year event-free survival for chemosensitive patients was 84%
      (95% CI, 72% to 96%) compared with 30% (95% CI, 2% to 58%) for chemorefractory
      patients before allo-SCT (P < .001). This nonmyeloablative regimen, with
      peritransplant rituximab, is safe and effective in patients with B-NHL.

PMID- 24315845
TI  - Pulmonary symptoms measured by the national institutes of health lung score
      predict overall survival, nonrelapse mortality, and patient-reported outcomes in
      chronic graft-versus-host disease.
AB  - The 2005 National Institutes of Health (NIH) Consensus Conference recommended
      assessment of lung function in patients with chronic graft-versus-host disease
      (GVHD) by both pulmonary function tests (PFTs) and assessment of pulmonary
      symptoms. We tested whether pulmonary measures were associated with nonrelapse
      mortality (NRM), overall survival (OS), and patient-reported outcomes (PRO).
      Clinician and patient-reported data were collected serially in a prospective,
      multicenter, observational study. Available PFT data were abstracted. Cox
      regression models were fit for outcomes using a time-varying covariate model for
      lung function measures and adjusting for patient and transplantation
      characteristics and nonlung chronic GVHD severity. A total of 1591 visits (496
      patients) were used in this analysis. The NIH symptom-based lung score was
      associated with NRM (P = .02), OS (P = .02), patient-reported symptoms (P < .001)
      and functional status (P < .001). Worsening of NIH symptom-based lung score over
      time was associated with higher NRM and lower survival. All other measures were
      not associated with OS or NRM; although, some were associated with patient
      reported lung symptoms. In conclusion, the NIH symptom-based lung symptom score
      of 0 to 3 is associated with NRM, OS, and PRO measures in patients with chronic
      GVHD. Worsening of the NIH symptom-based lung score was associated with increased
      mortality.

PMID- 24315846
TI  - Antithymocyte globulin in reduced-intensity conditioning regimen allows a high
      disease-free survival exempt of long-term chronic graft-versus-host disease.
AB  - Nonmyeloablative (NMA) regimens allow the use of allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) in patients considered unfit for standard
      myeloablative conditioning (MAC) regimens using high-dose alkylating agents with
      or without total body irradiation (TBI). Reduced-intensity conditioning (RIC)
      regimens, based on fludarabine (Flu), busulfan (Bu), and rabbit antithymocyte
      globulin (r-ATG), represent an intermediate alternative between NMA and MAC
      regimens. This platform was subsequently optimized by the introduction of i.v. Bu
      and the use of 5 mg/kg r-ATG, based on the hypothesis that these modifications
      would improve the safety of RIC allo-HSCT. Here we report a study conducted at
      our institution on 206 patients, median age 59 years, who underwent allo-HSCT
      after conditioning with Flu, 2 days of i.v. Bu, and 5 mg/kg r-ATG (FBx-ATG)
      between 2005 and 2012. The prevalence of grade III-IV acute graft-versus-host
      disease (GVHD) was 9%, and that of extensive chronic GVHD was 22%. Four-year
      nonrelapse mortality (NRM), relapse, and overall survival (OS) rates were 22%,
      36%, and 54%, respectively. NRM tended to be influenced by comorbidities
      (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] <3 versus
      HCT-CI >=3: 18% versus 27%; P = .075), but not by age (<60 years, 20% versus >=60
      years, 25%; P = .142). Disease risk significantly influenced relapse (2 years:
      low, 8%, intermediate, 28%, high, 34%; very high, 63%; P = .017). Both disease
      risk (hazard ratio [95% confidence interval]: intermediate, 2.1 [0.8 to 5.2], P =
      .127; high, 3.4 [1.3 to 9.1], P = .013; very high, 4.0 [1.1 to 14], P = .029) and
      HCT-CI (hazard ratio [95% confidence interval]: HCT-CI >=3, 1.7 (1.1 to 2.8), P =
      .018) influenced OS, but age and donor type did not. The FBx-ATG RIC regimen
      reported here is associated with low mortality and high long-term disease-free
      survival without persistent GVHD in both young and old patients. It represents a
      valuable platform for developing further post-transplantation strategies aimed at
      reducing the incidence of relapse, particularly in the setting of high-risk
      disease.

PMID- 24315847
TI  - Sexual assault, irresistible impulses, and forensic psychiatry in Sweden.
AB  - After forensic psychiatry was firmly established in Sweden in the 1930s, many
      rapists and individuals charged with assaulting children underwent a forensic
      psychiatric examination. The physicians found that most of them had not been "in
      control" of their senses or not "in complete control" of their senses at the time
      of the crime. If the court ordered a forensic psychiatric examination, the
      defendant had a very good chance of either being discharged or having his
      sentence reduced considerably. By the 1950s psychological perspectives began to
      dominate in forensic psychiatry. In the forensic records of the 1950s we can
      notice a shift from a biomedical to a socio-psychological perspective, and crime
      was increasingly related to conditions that were not seen as mental derangement
      from a legal point of view. As a result, it became less and less common, from the
      1950s onwards, for sentences to be commuted or defendants discharged. 

PMID- 24315848
TI  - Trends in stage-specific population-based survival of cancer patients in the
      Czech Republic in the period 2000-2008.
AB  - BACKGROUND: The objective of this study was to assess trends in overall and in
      stage-specific 5-year relative survival rates of the Czech cancer patients
      between periods 2000-2004 and 2005-2008. METHODS: All Czech cancer patients
      diagnosed between 1995 and 2008 were included in the analysis. Period analysis
      was employed to calculate 5-year relative survival for 21 cancers. RESULTS:
      Significant improvements in crude 5-year relative survival for 14 of 21 assessed
      types of cancer, including the most frequent diagnoses, such as, colorectal,
      prostate, breast, lung, kidney, pancreatic, and bladder cancer and melanoma, were
      identified. Moreover, in case of colorectal, lung, and prostate cancer,
      improvement in stage-specific 5-year relative survival was confirmed as
      statistically significant for all clinical stages. No diagnosis showed
      significant decrease in the 5-year relative survival. However, the 5-year
      relative survival remained poor in patients with metastatic cancers at diagnosis,
      particularly in case of liver, pancreatic, lung, and oesophageal cancer.
      CONCLUSIONS: The cancer-specific outcomes in the Czech Republic are improving.
      Nevertheless, despite the overall significant improvement in 5-year relative
      survival of most of the cancer diagnoses, the high proportion of patients
      primarily diagnosed with metastatic cancer still represents a substantial
      challenge for prevention and early detection.

PMID- 24315849
TI  - Proteomic profiling and post-translational modifications in human keratinocytes
      treated with Mucuna pruriens leaf extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens (Mp) is a plant belonging to the
      Fabaceae family, with several medicinal properties among which its potential to
      treat diseases where reactive oxygen species (ROS) play an important role in the
      pathogeneses. The aim was to investigate the effects of Mp leaf methanolic
      extract (MPME) on human keratinocytes protein expression and its role in
      preventing proteins oxidation after oxidative stress (OS) exposure. MATERIAL AND
      METHODS: The effects of MPME on HaCaT cells protein expression were evaluated
      treating cells with different concentrations of MPME, with glucose oxidase (GO,
      source of OS) and with MPME subsequently treated with GO. The protein patterns of
      treated HaCaT cells are analyzed by two-dimensional gel electrophoresis (2-DE)
      and compared with that of untreated HaCaT. Immunoblotting was then used to
      evaluate the role of MPME in preventing the 4-hydroxynonenal protein adducts (4
      HNE PAs) formation (marker of OS). RESULTS: Eighteen proteins, identified by mass
      spectrometry (LC-ESI-CID-MS/MS), were modulated distinctly by MPME in HaCaT.
      Overall, MPME counteract GO effect, reducing the GO-induced overexpression of
      several proteins involved in stress response (T-complex protein 1, Protein
      disulfide-isomerase A3, Protein DJ-1, and Stress-induced-phosphoprotein 1), in
      cell energy methabolism (Inorganic pyrophosphatase, Triosephosphate isomerase
      isoform 1, 2-phosphopyruvate-hydratase alpha-enolase, and Fructose-bisphosphate
      aldolase A isoform 1), in cytoskeletal organization (Cytokeratins 18, 9, 2,
      Cofilin-1, Annexin A2 and F-actin-capping protein subunit beta isoform 1) and in
      cell cycle progression (Eukaryotic translation initiation factor 5A-1 isoform B).
      In addition, MPME decreased the 4-HNE PAs levels, in particular on 2
      phosphopyruvate-hydratase alpha-enolase and Cytokeratin 9. CONCLUSIONS: Our
      findings show that MPME might be helpful in the treatment of OS-related skin
      diseases by preventing protein post-translational modifications (4-HNE PAs).

PMID- 24315850
TI  - In vitro genotoxicity of Melaleuca alternifolia essential oil in human
      lymphocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The volatile essential oil derived from the plant
      Melaleuca alternifolia, also called tea tree oil (TTO), is largely employed for
      its antimicrobial properties against several human pathogens. It is used in many
      topical formulations to treat cutaneous infections. AIM OF THE STUDY: Since very
      few studies have been done on the safety and toxicity of the crude Melaleuca
      alternifolia essential oil, current investigation evaluates the possible
      genotoxic effects of TTO in human lymphocyte cultures. MATERIAL AND METHODS: The
      composition of current TTO sample was determined by GC/MS and NMR. The level of
      cytotoxicity in TTO treated cultures was determined by decrease of mitotic index
      when compared to that in negative control. The genotoxic potential of TTO was
      assessed by the in vitro mammalian cell micronucleus and the chromosome
      aberrations (CA) tests. RESULTS: Twenty-seven compounds were identified,
      accounting for 98.9% of the constituents. Terpinen-4-ol (42.8%), gamma-terpinene
      (20.4%), p-cymene (9.6%), alpha-terpinene (7.9%), 1,8-cineole (3%), alpha
      terpineol (2.8%) and alpha-pinene (2.4%) were the major compounds of the oil
      sample. None of the tested TTO concentrations (95MUg/ml, 182MUg/ml and 365MUg/ml)
      caused a significant increase in the observed frequencies of micronuclei when
      compared to those in the untreated cultures (negative control). Additionally, no
      significant differences regarding the frequencies of CA were observed among the
      tested TTO concentrations and the negative control. CONCLUSIONS: Results
      demonstrate that TTO, in the tested concentrations, is not genotoxic in in vitro
      mammalian cells.

PMID- 24315851
TI  - Munronia pinnata (Wall.) Theob.: unveiling phytochemistry and dual inhibition of
      5-lipoxygenase and microsomal prostaglandin E2 synthase (mPGES)-1.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Preparations from Munronia pinnata (Wall.) Theob.
      are extensively used in traditional medicine in Sri Lanka for the treatment of
      inflammatory conditions. However, neither the pharmacological features nor the
      phytochemistry of this plant are explored in order to understand and rationalize
      the reported ethnobotanical significance. As 5-lipoxygenase (5-LO) and microsomal
      prostaglandin E2 synthase (mPGES)-1 are crucial enzymes in inflammatory
      disorders, we evaluated their inhibition by M. pinnata extracts and studied the
      chemical profile of the plant for the identification of relevant constituents.
      MATERIALS AND METHODS: Cell-free and cell-based assays were employed in order to
      investigate the suppression of 5-LO and mPGES-1 activity. Cell viability, radical
      scavenger activities, and inhibition of reactive oxygen species formation (ROS)
      in neutrophils were studied to assess cytotoxic and antioxidant effects. Gas and
      liquid chromatography coupled to mass spectrometric analysis enabled the
      characterization of secondary metabolites. RESULTS: The n-hexane extract of M.
      pinnata efficiently suppressed 5-LO activity in stimulated human neutrophils
      (IC50 =8.7ug/ml) and potently inhibited isolated human recombinant 5-LO (IC50
      =0.48ug/ml) and mPGES-1 (IC50 =1.0ug/ml). In contrast, no significant radical
      scavenging activity or suppression of ROS formation was observed, and neutrophil
      viability was unaffected. The phytochemistry of the plant was unveiled for the
      first time and phytosterols, fatty acids, sesquiterpenes and several other types
      of secondary metabolites were identified. CONCLUSIONS: Together, potent
      inhibition of 5-LO and mPGES-1 activity, without concomitant antioxidant activity
      and cytotoxic effects, rationalizes the ethnopharmacological use of M. pinnata as
      anti-inflammatory remedy. Detailed chromatographic/mass spectrometric analysis
      reveals discrete chemical structures of relevant constituents.

PMID- 24315852
TI  - Short-term administration of an aqueous extract of kalanchoe integra var. crenata
      (Andr.) Cuf leaves produces no major organ damage in Sprague-Dawley rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kalanchoe intergra (Ki) leaf extract is an orally
      administered multipurpose plant medicine in Ghana and other parts of the world
      for the treatment of ulcers, pain and adenoma of the prostate gland. There is
      paucity of information concerning its short-term usage. The present study is
      aimed at conducting histopathological and biochemical studies in a 14-day sub
      acute toxicity studies using female Sprague-Dawley rats. MATERIALS AND METHODS:
      Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute
      toxicity studies was conducted using 2 week old nulliparous and non-pregnant
      female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a
      dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an
      equivalent volume of distilled water (as vehicle) by gastric lavage.
      Histopathological studies of major organs and blood chemistry analysis were
      performed on blood obtained via cardiac puncture into EDTA tubes after
      euthanisation. RESULTS: There was a significant decrease in urea (p<0.016) and
      creatinine levels (p<0.001) in both the high and low dose groups. There was an
      increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST
      rather decreased significantly in both the high and low dose groups (p<0.0001).
      Histopathological results did not show any abnormalities in all the H&E stained
      paraffin sections. Thus the photomicrographs of the liver, kidney and heart were
      within histopathological limits. CONCLUSION: Ki leaf extract is non-toxic when
      administered by the oral route over a time period of 14 days at the above doses.

PMID- 24315853
TI  - Dynamics of TET family expression in porcine preimplantation embryos is related
      to zygotic genome activation and required for the maintenance of NANOG.
AB  - Dynamic changes in DNA methylation are observed during embryo development. Recent
      studies show that the TET family is involved in these changes by converting 5
      methylcytosine (5mec) to 5-hydroxymethylcytosine (5hmec). Specifically, TET3 is
      responsible for the conversion in the early stages, and then TET1 is a key
      regulator at later stages of embryo development. From previous mouse reports and
      our preliminary data in porcine embryos, we hypothesized that TET1 becomes the
      main regulator at the time of the maternal to zygotic transition (MZT).
      Transcript abundance of TET3 was high only at the zygote and 2-cell stage. The
      abundance of TET1 mRNA was high in the blastocysts and TET1 protein was present
      at the 4-cell stage and the blastocysts. The dynamic was similar in porcine
      somatic cell nuclear transfer (SCNT) embryos however; abnormally upregulated TET3
      was detected at the 4-cell stage. When transcription or translation was blocked
      at the 2-cell stage, TET3 mRNA remained high at the 4-cell stage suggesting that
      degradation of TET3 is related to the MZT. Downregulation of TET3 before
      fertilization resulted in the reduction of 5hmec in zygotes indicating that TET3
      is a key molecule for 5hmec synthesis. This misregulation of 5hmec in zygotes
      also affected the level of NANOG expression in the blastocysts. We show here that
      the porcine TET family shows dynamic expression patterns during embryogenesis,
      and is responsible for the appearance of 5hmec in the zygotes by TET3. This
      appearance of 5hmec in zygote is important for the expression of NANOG in the
      blastocysts. 

PMID- 24315855
TI  - Nitric oxide-releasing poly(vinyl alcohol) film for increasing dermal
      vasodilation.
AB  - Pathological conditions associated with the impairment of nitric oxide (NO)
      production in the vasculature, such as Raynaud's syndrome and diabetic
      angiopathy, have stimulated the development of new biomaterials capable of
      delivering NO topically. With this purpose, we modified poly(vinyl-alcohol) (PVA)
      by chemically crosslinking it via esterification with mercaptosuccinic acid. This
      reaction allowed the casting of sulfhydrylated PVA (PVA-SH) films. Differential
      scanning calorimetry and X-ray diffractometry showed that the crosslinking
      reaction completely suppressed the crystallization of PVA, leading to a non
      porous film with a homogeneous distribution of -SH groups. The remaining free
      hydroxyl groups in the PVA-SH network conferred partial hydrophylicity to the
      material, which was responsible for a swelling degree of ca. 110%. The PVA-SH
      films were subjected to an S-nitrosation reaction of the -SH groups, yielding a
      PVA containing S-nitrosothiol groups (PVA-SNO). Amperometric and
      chemiluminescence measurements showed that the PVA-SNO films were capable of
      releasing NO spontaneously after immersion in physiological medium. Laser Doppler
      flowmetry, used to assess the blood flow in the dermal microcirculation, showed
      that the topical application of hydrated PVA-SNO films on the health skin led to
      a dose- and time-dependent increase of more than 5-fold in the dermal baseline
      blood flow in less than 10min, with a prolonged action of more than 4h during
      continuous application. These results show that PVA-SNO films might emerge as a
      new material with potential for the topical treatment of microvascular skin
      disorders.

PMID- 24315856
TI  - Low density lipoprotein induces upregulation of vasoconstrictive endothelin type
      B receptor expression.
AB  - Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and
      ischemic cerebro- and cardiovascular diseases. The present study was designed to
      examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive
      ET(B) receptor expression and if extracellular signal-regulated kinases 1 and 2
      (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are
      involved in this process. Rat mesenteric artery segments were organ cultured in
      the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and
      2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ET(B)
      receptor expression was studied using a sensitive myograph, real-time PCR and
      Western blot. LDL (11, 22 and 44 mg protein/L) concentration-dependently induced
      upregulation of vasoconstrictive ETB receptor expression with increase in the
      receptor-mediated vasoconstriction, elevated levels of the ET(B) receptor mRNA
      and protein expressions, and activation of ERK1/2 and p38 MAPK. Blockage of
      ERK1/2 and p38 MAPK signal pathways using MEK1/2 inhibitors (PD98059 and U0126)
      or p38 inhibitors (SB203580 and SB239063) significantly abolished the LDL-induced
      upregulation of vasoconstrictive ET(B) receptor expression. Actinomycin D
      (general transcriptional inhibitor) almost completely inhibited the LDL effects.
      In conclusion, LDL induces upregulation of vasoconstrictive ET(B) receptor
      expression through activation of ERK1/2 and p38 MAPK signal pathway-dependent
      transcriptional mechanisms.

PMID- 24315854
TI  - Signaling mechanisms controlling cranial placode neurogenesis and delamination.
AB  - The neurogenic cranial placodes are a unique transient epithelial niche of neural
      progenitor cells that give rise to multiple derivatives of the peripheral nervous
      system, particularly, the sensory neurons. Placode neurogenesis occurs throughout
      an extended period of time with epithelial cells continually recruited as neural
      progenitor cells. Sensory neuron development in the trigeminal, epibranchial,
      otic, and olfactory placodes coincides with detachment of these neuroblasts from
      the encompassing epithelial sheet, leading to delamination and ingression into
      the mesenchyme where they continue to differentiate as neurons. Multiple
      signaling pathways are known to direct placodal development. This review defines
      the signaling pathways working at the finite spatiotemporal period when neuronal
      selection within the placodes occurs, and neuroblasts concomitantly delaminate
      from the epithelium. Examining neurogenesis and delamination after initial
      placodal patterning and specification has revealed a common trend throughout the
      neurogenic placodes, which suggests that both activated FGF and attenuated Notch
      signaling activities are required for neurogenesis and changes in epithelial cell
      adhesion leading to delamination. We also address the varying roles of other
      pathways such as the Wnt and BMP signaling families during sensory neurogenesis
      and neuroblast delamination in the differing placodes. 

PMID- 24315857
TI  - Scale-down of vinegar production into microtiter plates using a custom-made lid.
AB  - As an important food preservative and condiment, vinegar is widely produced in
      industry by submerged acetic acid bacteria cultures. Although vinegar production
      is established on the large scale, up to now suitable microscale cultivation
      methods, e.g. using microtiter plates, are missing to enable high-throughput
      cultivation and to optimize fermentation conditions. In order to minimize
      evaporation losses of ethanol and acetic acid in a 48-well microtiter plate
      during vinegar production a new custom-made lid was developed. A diffusion model
      was used to calculate the dimensions of a hole in the lid to guarantee a suitable
      oxygen supply and level of ventilation. Reference fermentation was conducted in a
      9-L bioreactor to enable the calculation of the proper cultivation conditions in
      the microtiter plate. The minimum dissolved oxygen tensions in the microtiter
      plate were between 7.5% and 23% of air saturation and in the same range as in the
      9-L bioreactor. Evaporation losses of ethanol and acetic acid were less than 5%
      after 47 h and considerably reduced compared to those of microtiter plate
      fermentations with a conventional gas-permeable seal. Furthermore, cultivation
      times in the microtiter plate were with about 40 h as long as in the 9-L
      bioreactor. In conclusion, microtiter plate cultivations with the new custom-made
      lid provide a platform for high-throughput studies on vinegar production. Results
      are comparable to those in the 9-L bioreactor.

PMID- 24315858
TI  - Mechanism of cleavage of alpha-synuclein by the 20S proteasome and modulation of
      its degradation by the RedOx state of the N-terminal methionines.
AB  - Alpha-synuclein is a small protein implicated in the pathophysiology of
      Parkinson's disease (PD). We have investigated the mechanism of cleavage of alpha
      synuclein by the 20S proteasome. Alpha-synuclein interacts with the C8 (alpha7)
      subunit of the proteasome. The N-terminal part of alpha-synuclein (amino acids 1
      60) is essential for its proteasomal degradation and analysis of peptides
      released from proteasomal digestion allows concluding that initial cleavages
      occur within the N-terminal region of the molecule. Aggregated alpha-synucleins
      are also degraded by the proteasome with a reduced rate, likely due to Met
      oxidation. In fact, mild oxidation of alpha-synuclein with H2O2 resulted in the
      inhibition of its degradation by the proteasome, mainly due to oxidation of Met 1
      and 5 of alpha-synuclein. The inhibition was reversed by treatment of the
      oxidized protein with methionine sulfoxide reductases (MsrA plus MsrB).
      Similarly, treatment with H2O2 of N2A cells transfected with alpha-synuclein
      resulted in the inhibition of its degradation that was also reverted by co
      transfection of MsrA plus MsrB. These results clearly indicate that oxidative
      stress, a common feature of PD and other synucleinopathies, promotes a RedOx
      change in the proteostasis of alpha-synuclein due to Met oxidation and reduced
      proteasomal degradation; compromised reversion of those oxidative changes would
      result in the accumulation of oxidative damaged alpha-synuclein likely
      contributing to the pathogenesis of PD. 

PMID- 24315859
TI  - Intrapartum antibiotic prophylaxis for Group B Streptococcus: has the time come
      to wait more than 4 hours?
AB  - Despite progress in preventing infant group B streptococcal disease, group B
      streptococcus remains the leading cause of early-onset neonatal sepsis in the
      United States. Fortunately, most women who are colonized with group B
      streptococcus receive therapy and antibiotic prophylaxis is effective. However,
      the only factor associated with missed chemoprophylaxis is the short duration of
      time between hospital admission and delivery. Although antibiotic prophylaxis
      given for at least 2 hours shows some pharmacological benefit, the most effective
      method of preventing early-onset group B streptococcus disease is 4 hours of
      therapy. Intrapartum management strategies might be modified to improve the
      efficacy of antibiotic exposure. Obstetricians should consider strengthening the
      beneficial effect of intrapartum antibiotic prophylaxis for infants exposed to
      group B streptococcus by providing at least 4 hours of treatment coverage. 

PMID- 24315860
TI  - Perinatal- and procedure-related outcomes following radiofrequency ablation in
      monochorionic pregnancy.
AB  - OBJECTIVE: We sought to assess the efficacy, complication rates, and outcomes for
      complex monochorionic pregnancies undergoing selective fetal reduction using
      radiofrequency ablation (RFA). STUDY DESIGN: In this prospective observational
      study, 100 consecutive cases of selective fetal reduction using RFA were
      analyzed. All cases were managed at the Centre for Fetal Care at Queen
      Charlotte's and Chelsea Hospital in London. Indications for offering RFA, details
      of the procedure, and pregnancy outcomes were collected and analyzed. RESULTS:
      The main indications for RFA were discordant fetal anomaly and twin-twin
      transfusion syndrome. Overall live birth rate was 78% and the median gestation at
      delivery was 35.15 weeks. Delivery <32 weeks' gestation occurred in 17.9% of
      cases. Postprocedure abnormal antenatal magnetic resonance imaging occurred in 3%
      of cases. There was no statistical difference in outcomes with regard to
      gestation when the procedure was performed or the indication for the RFA.
      CONCLUSION: RFA appears to be a reasonable option for selective fetal reduction
      in complex monochorionic pregnancies with an overall survival rate of 78%.

PMID- 24315861
TI  - Measurement and risk adjustment of prelabor cesarean rates in a large sample of
      California hospitals.
AB  - OBJECTIVE: Prelabor cesareans in women without a prior cesarean is an important
      quality measure, yet one that is seldom tracked. We estimated patient-level risks
      and calculated how sensitive hospital rankings on this proposed quality metric
      were to risk adjustment. STUDY DESIGN: This retrospective cohort study linked
      Californian patient data from the Agency for Healthcare Research and Quality with
      hospital-level operational and financial data. Using the outcome of primary
      prelabor cesarean, we estimated patient-level logistic regressions in
      progressively more detailed models. We assessed incremental fit and
      discrimination, and aggregated the predicted patient-level event probabilities to
      construct hospital-level rankings. RESULTS: Of 408,355 deliveries by women
      without prior cesareans at 254 hospitals, 11.0% were prelabor cesareans.
      Including age, ethnicity, race, insurance, weekend and unscheduled admission, and
      12 well-known patient risk factors yielded a model c-statistic of 0.83. Further
      maternal comorbidities, and hospital and obstetric unit characteristics only
      marginally improved fit. Risk adjusting hospital rankings led to a median
      absolute change in rank of 44 places compared to rankings based on observed
      rates. Of the 48 (49) hospitals identified as in the best (worst) quintile on
      observed rates, only 23 (18) were so identified by the risk-adjusted model.
      CONCLUSION: Models predict primary prelabor cesareans with good discrimination.
      Systematic hospital-level variation in patient risk factors requires risk
      adjustment to avoid considerably different classification of hospitals by outcome
      performance. An opportunity exists to define this metric and report such risk
      adjusted outcomes to stakeholders.

PMID- 24315862
TI  - Brainstem and cerebellar differences and their association with neurobehavior in
      term small-for-gestational-age fetuses assessed by fetal MRI.
AB  - OBJECTIVE: We tested the hypothesis whether small-for-gestational-age (SGA)
      fetuses have different brain stem and cerebellar morphometry when compared with
      appropriate-for-gestational-age (AGA) fetuses and whether the differences in
      these structures were associated with their neonatal neurobehavior. STUDY DESIGN:
      Magnetic resonance imaging was performed on 51 SGA fetuses and 47 AGA fetuses at
      37 weeks' gestation. Pontine width, medullar width, vermian width and height,
      cerebellar primary fissure's depth, and cerebellar volume were measured and
      corrected by biparietal diameter and cerebellar volume by total intracranial
      volume. Ratios were compared between cases and control subjects. The association
      between morphometric differences and neurobehavioral outcome in SGAs was tested.
      RESULTS: Brainstem and cerebellar ratios were significantly larger in SGA
      fetuses: pontine width, SGA 0.143 +/- 0.01 vs AGA 0.135 +/- 0.01 (P < .01);
      medullar width, SGA 0.088 +/- 0.01 vs AGA 0.083 +/- 0.01 (P = .03); vermian
      width, SGA 0.181 +/- 0.03 vs AGA 0.162 +/- 0.02 (P < .01); vermian height, SGA
      0.235 +/- 0.03 vs AGA 0.222 +/- 0.01 (P < .01); cerebellar volume, SGA 0.042 +/-
      0.01 vs AGA 0.038 +/- 0.00 (P = .04); with deeper cerebellar primary fissure in
      SGAs, SGA 0.041 +/- 0.01 vs AGA 0.035 +/- 0.01 (P = .01). Medullar, cerebellar
      biometries, and volumetry were significantly associated with different Neonatal
      Behavioral Assessment Scale cluster scores in SGA infants. CONCLUSION: Brain stem
      and cerebellar morphometric measurements are significantly different in term SGA
      fetuses, which are associated significantly with their neurobehavioral outcome.
      This finding supports the existence of brain microstructural changes in SGA
      fetuses and lays the basis for potential image biomarkers to detect fetuses who
      are at risk.

PMID- 24315863
TI  - Cloning and expression analysis of tyrosine hydroxylase and changes in
      catecholamine levels in brain during ontogeny and after sex steroid analogues
      exposure in the catfish, Clarias batrachus.
AB  - Tyrosine hydroxylase (Th) is the rate-limiting enzyme for catecholamine (CA)
      biosynthesis and is considered to be a marker for CA-ergic neurons, which
      regulate the levels of gonadotropin-releasing hormone in brain and gonadotropins
      in the pituitary. In the present study, we cloned full-length cDNA of Th from the
      catfish brain and evaluated its expression pattern in the male and female brain
      during early development and after sex-steroid analogues treatment using
      quantitative real-time PCR. We measured the CA levels to compare our results on
      Th. Cloned Th from catfish brain is 1.591 kb, which encodes a putative protein of
      458 amino acid residues and showed high homology with other teleosts. The tissue
      distribution of Th revealed ubiquitous expression in all the tissues analyzed
      with maximum expression in male and female brain. Copy number analysis showed two
      fold more transcript abundance in the female brain when compared with the male
      brain. A differential expression pattern of Th was observed in which the mRNA
      levels were significantly higher in females compared with males, during early
      brain development. CAs, l-3,4-dihydroxyphenylalanine, dopamine, and
      norepinephrine levels measured using high-performance liquid chromatography with
      electrochemical detection in the developing male and female brain confirmed the
      prominence of the CA-ergic system in the female brain. Sex-steroid analogue
      treatment using methyltestosterone and ethinylestradiol confirmed our findings of
      the differential expression of Th related to CA levels.

PMID- 24315864
TI  - A multi-locus molecular phylogeny for Australia's iconic Jacky Dragon (Agamidae:
      Amphibolurus muricatus): phylogeographic structure along the Great Dividing Range
      of south-eastern Australia.
AB  - Jacky dragons (Amphibolurus muricatus) are ubiquitous in south-eastern Australia
      and were one of the first Australian reptiles to be formally described. Because
      they are so common, Jacky dragons are widely used as a model system for research
      in evolutionary biology and ecology. In addition, their distribution along the
      Great Dividing Range of eastern Australia provides an opportunity to examine the
      influence of past biogeographical processes, particularly the expansion and
      contraction of forest habitats, on the diversification of this iconic agamid
      lizard. We generated sequence data for two mitochondrial and three nuclear DNA
      loci (4251base pairs) for 62 Jacky dragons sampled from throughout their
      distribution. Phylogenetic analyses based on maximum likelihood and Bayesian
      species-tree methods revealed five geographically structured clades separated by
      up to 6% mitochondrial and 0.7% nuclear sequence divergence. We also quantified
      body proportion variation within and between these genetic clades for more than
      500 specimens and found no evidence of any significant differentiation in body
      proportions across their range. Based on body proportion homogeneity and lack of
      resolution in the nuclear loci, we do not support taxonomic recognition of any of
      the mitochondrial clades. Instead, A. muricatus is best thought of as a single
      species with phylogeographic structure. The genetic patterns observed in the
      Jacky dragon are consistent with fragmented populations reduced to multiple
      refugia during cold, arid phases when forested habitats were greatly restricted.
      Consequently, the inferred biogeographic barriers for this taxon appear to be in
      line with lowland breaks in the mountain ranges. Our results are congruent with
      studies of other reptiles, frogs, mammals, birds and invertebrates, and together
      highlight the overarching effects of widespread climatic and habitat fluctuations
      along the Great Dividing Range since the Pliocene. 

PMID- 24315865
TI  - Sampling strategies for improving tree accuracy and phylogenetic analyses: a case
      study in ciliate protists, with notes on the genus Paramecium.
AB  - In order to assess how dataset-selection for multi-gene analyses affects the
      accuracy of inferred phylogenetic trees in ciliates, we chose five genes and the
      genus Paramecium, one of the most widely used model protist genera, and compared
      tree topologies of the single- and multi-gene analyses. Our empirical study shows
      that: (1) Using multiple genes improves phylogenetic accuracy, even when their
      one-gene topologies are in conflict with each other. (2) The impact of missing
      data on phylogenetic accuracy is ambiguous: resolution power and topological
      similarity, but not number of represented taxa, are the most important criteria
      of a dataset for inclusion in concatenated analyses. (3) As an example, we tested
      the three classification models of the genus Paramecium with a multi-gene based
      approach, and only the monophyly of the subgenus Paramecium is supported. 

PMID- 24315866
TI  - Toward a Tree-of-Life for the boas and pythons: multilocus species-level
      phylogeny with unprecedented taxon sampling.
AB  - Snakes in the families Boidae and Pythonidae constitute some of the most
      spectacular reptiles and comprise an enormous diversity of morphology, behavior,
      and ecology. While many species of boas and pythons are familiar, taxonomy and
      evolutionary relationships within these families remain contentious and fluid. A
      major effort in evolutionary and conservation biology is to assemble a
      comprehensive Tree-of-Life, or a macro-scale phylogenetic hypothesis, for all
      known life on Earth. No previously published study has produced a species-level
      molecular phylogeny for more than 61% of boa species or 65% of python species.
      Using both novel and previously published sequence data, we have produced a
      species-level phylogeny for 84.5% of boid species and 82.5% of pythonid species,
      contextualized within a larger phylogeny of henophidian snakes. We obtained new
      sequence data for three boid, one pythonid, and two tropidophiid taxa which have
      never previously been included in a molecular study, in addition to generating
      novel sequences for seven genes across an additional 12 taxa. We compiled an 11
      gene dataset for 127 taxa, consisting of the mitochondrial genes CYTB, 12S, and
      16S, and the nuclear genes bdnf, bmp2, c-mos, gpr35, rag1, ntf3, odc, and
      slc30a1, totaling up to 7561 base pairs per taxon. We analyzed this dataset using
      both maximum likelihood and Bayesian inference and recovered a well-supported
      phylogeny for these species. We found significant evidence of discordance between
      taxonomy and evolutionary relationships in the genera Tropidophis, Morelia,
      Liasis, and Leiopython, and we found support for elevating two previously
      suggested boid species. We suggest a revised taxonomy for the boas (13 genera, 58
      species) and pythons (8 genera, 40 species), review relationships between our
      study and the many other molecular phylogenetic studies of henophidian snakes,
      and present a taxonomic database and alignment which may be easily used and built
      upon by other researchers. 

PMID- 24315867
TI  - Hiding in the highlands: evolution of a frog species complex of the genus
      Ptychadena in the Ethiopian highlands.
AB  - The Ethiopian highlands are a biodiversity hotspot characterized by a high level
      of endemism, particularly in amphibians. Frogs of the genus Ptychadena have
      experienced an evolutionary radiation in these highlands. Thus, this group
      provides an excellent opportunity to study the process of speciation in this
      important biogeographic area. We sequenced two mitochondrial (16S and COI) and
      four nuclear (Rag-1, CXCR4, NCX1 and Tyr) genes in a sample of 236 frogs from 49
      Ethiopian localities. Phylogenetic analyses of the mitochondrial genes revealed
      the presence of eight divergent mitochondrial lineages. We uncovered a near
      perfect concordance between these lineages and genetic clusters based on nuclear
      sequences. A Bayesian species delimitation analysis confirmed that these eight
      lineages correspond to eight genetically isolated populations which may represent
      eight species. Some of these species have already been recognized due to their
      distinct morphology (P. cooperi, P. nana and P. erlangeri) but we determined that
      the species P. neumanni is a complex of 5 cryptic species, thus increasing
      substantially the number of species in this genus and for this country. We
      resolved the phylogeny of Ethiopian highland Ptychadena using a species tree
      approach and determined that Ptychadena species group on the phylogeny according
      to their habitat preference. We propose that the diversity of Ethiopian
      Ptychadena results from an early phase of specialization to distinct elevations
      followed by a phase of ecological diversification within each elevational range.
      We estimated that the early phase of diversification of Ethiopian Ptychadena
      probably occurred in the late Miocene and the most recent speciation events in
      the late-Pliocene or Pleistocene. 

PMID- 24315868
TI  - A molecular phylogeny of Pacific honeyeaters (Aves: Meliphagidae) reveals
      extensive paraphyly and an isolated Polynesian radiation.
AB  - We investigated the molecular phylogenetic placement of 14 species of Pacific
      island honeyeaters (Aves: Meliphagidae) in the broader context of an existing
      family-level phylogeny. We examined the evolutionary history of Pacific
      honeyeater lineages to assess the accuracy of current taxonomies and to evaluate
      their biogeographic history. We compare these biogeographic patterns to other
      Pacific birds to identify emergent patterns across lineages. We found strong
      support for a previously unknown endemic radiation in central Polynesia, which
      comprises five genera: Meliarchus, Guadalcanaria, Gymnomyza, Xanthotis, and
      Foulehaio. Conversely, other Pacific lineages were found to be strongly allied
      with continental radiations (e.g., Philemon eichhorni, P. cockerelli, and
      Lichmera incana). Our results necessitated taxonomic changes, both at the generic
      level (e.g., Xanthotis, Melidectes/Vosea, and Glycifohia/Gliciphila) and
      regarding species limits within polytypic species. Here, we discuss species
      limits in Foulehaio and Gymnomyza and recommend elevating three nominal
      subspecies of Foulehaio to species status, each of which forms well
      differentiated clades. 

PMID- 24315869
TI  - Neuroprotective biflavonoids of Chamaecyparis obtusa leaves against glutamate
      induced oxidative stress in HT22 hippocampal cells.
AB  - Four biflavonoids (1-4), five flavonoids glycosides (5-9), two catechins (10,
      11), two lignans (12-13), neolignan glycoside (14) and phenylpropanoid glycoside
      (15) were isolated from the leaves of Chamaecyparis obtusa (Cupressaceae).
      Neuroprotective effects of the isolated compounds were evaluated employing HT22
      mouse hippocampal cells, a model system to study glutamate-induced oxidative
      stress. The glutamate injured HT22 cells were protected significantly by
      amentoflavone (3), ginkgetin (4) and (-)-epitaxifolin 3-O-beta-D-xylopyranoside
      (9). The reduced activities of antioxidant enzymes, superoxide dismutase (SOD),
      glutathione reductase (GR) in response to high concentration of glutamate were
      preserved by pre-treatment of 3, 4 or 9, while the activities of glutathione
      peroxidase (Gpx) and catalase (CAT) were little affected. The reduced content of
      GSH induced by glutamate was also recovered by 3, 4 or 9 in accommodation with
      the decrease in ROS production. In addition, the phosphorylation of ERK1/2
      induced by glutamate insult was clearly prevented by 3, while little changed by
      4. Taken together, amentoflavone (3), ginkgetin (4) and (-)-epitaxifolin 3-O-beta
      D-xylopyranoside (9) derived from C. obtusa could protect HT22 neuronal cells
      against glutamate-induced oxidative damage through preserving antioxidant enzymes
      activities and/or inhibiting ERK1/2 activation. 

PMID- 24315870
TI  - Protective effects of meat from lambs on selenium nanoparticle supplemented diet
      in a mouse model of polycyclic aromatic hydrocarbon-induced immunotoxicity.
AB  - Increased environmental oxidative stress caused primarily by chemicals like
      polycyclic aromatic hydrocarbons, plays significant role in human diseases. A
      representative compound, 7,12-dimethylbenz(a)anthracene (DMBA), was used for
      modeling oxidative damages including the significant decrease of the antioxidant
      capacity of the blood. Selenium has antioxidant effects but with a narrow
      therapeutic window. In our current studies to avoid accidental overdose and
      toxicity selenium was given to meat-producing animals. The standard rodent diet
      of mice was replaced by meat from lambs either on standard or selenium-enriched
      diet. Selenium concentration of lamb meat was enhanced three times by nano
      selenium administration and an increase in the antioxidant capacity of the blood
      of mice was measured after the indirect selenium supplementation. Protective
      effects were also observed against DMBA-induced immunotoxicity. Twice the amount
      of white blood cells and among them three times more phagocytes survived.
      Similarly, in their renewal system in bone marrow twice the amount of cells
      survived and regenerative capacity of granulopoiesis was four times higher than
      in control DMBA-damaged mice. Our findings suggest functional dietary benefits of
      lamb meat enriched with selenium by feeding lambs with nanoparticle selenium
      supplements. 

PMID- 24315871
TI  - Minilaparoscopic nerve sparing radical hysterectomy in locally advanced cervical
      cancer after neoadjuvant radiochemotherapy.

PMID- 24315872
TI  - Sentinel lymph node biopsy algorithm: can it be a universal method for midline
      tumors?

PMID- 24315873
TI  - ER stress-inducible ATF3 suppresses BMP2-induced ALP expression and activation in
      MC3T3-E1 cells.
AB  - Endoplasmic reticulum (ER) stress suppresses osteoblast differentiation.
      Activating transcription factor (ATF) 3, a member of the ATF/cAMP response
      element-binding protein family of transcription factors, is induced by various
      stimuli including cytokines, hormones, DNA damage, and ER stress. However, the
      role of ATF3 in osteoblast differentiation has not been elucidated. Treatment
      with tunicamycin (TM), an ER stress inducer, increased ATF3 expression in the
      preosteoblast cell line, MC3T3-E1. Overexpression of ATF3 inhibited bone
      morphogenetic protein 2-stimulated expression and activation of alkaline
      phosphatase (ALP), an osteogenic marker. In addition, suppression of ALP
      expression by TM treatment was rescued by silencing of ATF3 using shRNA. Taken
      together, these data indicate that ATF3 is a novel negative regulator of
      osteoblast differentiation by specifically suppressing ALP gene expression in
      preosteoblasts. 

PMID- 24315874
TI  - Murine T cell activation is regulated by surfen (bis-2-methyl-4-amino-quinolyl-6
      carbamide).
AB  - Surfen (bis-2-methyl-4-amino-quinolyl-6-carbamide) binds to glycosaminoglycans
      (GAGs) and has been shown to influence their function, and the function of
      proteoglycans (complexes of GAGs linked to a core protein). T cells synthesize,
      secrete and express GAGs and proteoglycans which are involved in several aspects
      of T cell function. However, there are as yet no studies on the effect of GAG
      binding agents such as surfen on T cell function. In this study, surfen was found
      to influence murine T cell activation. Doses between 2.5 and 20 MUM produced a
      graduated reduction in the proliferation of T cells activated with anti-CD3/CD28
      antibody-coated T cell expander beads. Surfen (20 mg/kg) was also administered to
      mice treated with anti-CD3 antibody to activate T cells in vivo. Lymphocytes from
      surfen-treated mice also showed reduced proliferation and lymph node cell counts
      were reduced. Surfen reduced labeling with a cell viability marker (7-ADD) but to
      a much lower extent than its effect on proliferation. Surfen also reduced CD25
      (the alpha-subunit of the interleukin (IL)-2 receptor) expression with no effect
      on CD69 expression in T cells treated in vivo but not in vitro. When receptor
      activation was bypassed by treating T cells in vitro with phorbyl myristate
      acetate (10 ng/ml) and ionomycin (100 ng/ml), surfen treatment either increased
      proliferation (10 MUM) or had no effect (2.5, 5 and 20 MUM). In vitro treatment
      of T cells with surfen had no effect on IL-2 or interferon-gamma synthesis and
      did not alter proliferation of the IL-2 dependent cell line CTLL-2. The effect of
      surfen was antagonized dose-dependently by co-treatment with heparin sulfate. We
      conclude that surfen inhibits T cell proliferation in vitro and in vivo. When T
      cell receptor-driven activation is bypassed surfen had a neutral or stimulatory
      effect on T cell proliferation. The results imply that endogenous GAGs and
      proteoglycans play a complex role in promoting or inhibiting different aspects of
      T cell activation.

PMID- 24315876
TI  - A label-free electrochemical biosensor for highly sensitive and selective
      detection of DNA via a dual-amplified strategy.
AB  - In this work, by combining the enzymatic recycling reaction with the DNA
      functionalized gold nanoparticles (AuNPs)-based signal amplification, we have
      developed an electrochemical biosensor for label-free detection of DNA with high
      sensitivity and selectivity. In the new designed biosensor, a hairpin-structured
      probe HP was designed to hybridize with target DNA first, and an exonuclease
      ExoIII was chosen for the homogeneous enzymatic cleaving amplification. The
      hybridization of target DNA with the probe HP induced the partial cleavage of the
      probe HP by ExoIII to release the enzymatic products. The enzymatic products
      could then hybridize with the hairpin-structured capture probe CP modified on the
      electrode surface. Finally, DNA functionalized AuNPs was further employed to
      amplify the detection signal. Due to the capture of abundant methylene blue (MB)
      molecules by both the multiple DNAs modified on AuNPs surface and the
      hybridization product of capture DNA and enzymatic products, the designed
      biosensor achieved a high sensitivity for target DNA, and a detection limit of
      0.6 pM was obtained. Due to the employment of two hairpin-structured probes, HP
      and CP, the proposed biosensor also exhibited high selectivity to target DNA.
      Moreover, since ExoIII does not require specific recognition sequences, the
      proposed biosensor might provide a universal design strategy to construct DNA
      biosensor which can be applied in various biological and medical samples.

PMID- 24315875
TI  - Pathogen induced chemo-attractant hepoxilin A3 drives neutrophils, but not
      eosinophils across epithelial barriers.
AB  - Pathogen induced migration of neutrophils across mucosal epithelial barriers
      requires epithelial production of the chemotactic lipid mediator, hepoxilin A3
      (HXA3). HXA3 is an eicosanoid derived from arachidonic acid. Although eosinophils
      are also capable of penetrating mucosal surfaces, eosinophilic infiltration
      occurs mainly during allergic processes whereas neutrophils dominate mucosal
      infection. Both neutrophils and eosinophils can respond to chemotactic gradients
      of certain eicosanoids, however, it is not known whether eosinophils respond to
      pathogen induced lipid mediators such as HXA3. In this study, neutrophils and
      eosinophils were isolated from human blood and placed on the basolateral side of
      polarized epithelial monolayers grown on permeable Transwell filters and
      challenged by various chemotactic gradients of distinct lipid mediators. We
      observed that both cell populations migrated across epithelial monolayers in
      response to a leukotriene B4 (LTB4) gradient, whereas only eosinophils migrated
      toward a prostaglandin D2 (PGD2) gradient. Interestingly, while pathogen induced
      neutrophil trans-epithelial migration was substantial, pathogen induced
      eosinophil trans-epithelial migration was not observed. Further, gradients of
      chemotactic lipids derived from pathogen infected epithelial cells known to be
      enriched for HXA3 as well as purified HXA3 drove significant numbers of
      neutrophils across epithelial barriers, whereas eosinophils failed to respond to
      these gradients. These data suggest that although the eicosanoid HXA3 serves as
      an important neutrophil chemo-attractant at mucosal surfaces during pathogenic
      infection, HXA3 does not appear to exhibit chemotactic activity toward
      eosinophils. 

PMID- 24315878
TI  - All electronic approach for high-throughput cell trapping and lysis with
      electrical impedance monitoring.
AB  - We present a portable lab-on-chip device for high-throughput trapping and lysis
      of single cells with in-situ impedance monitoring in an all-electronic approach.
      The lab-on-chip device consists of microwell arrays between transparent
      conducting electrodes within a microfluidic channel to deliver and extract cells
      using alternating current (AC) dielectrophoresis. Cells are lysed with high
      efficiency using direct current (DC) electric fields between the electrodes.
      Results are presented for trapping and lysis of human red blood cells. Impedance
      spectroscopy is used to estimate the percentage of filled wells with cells and to
      monitor lysis. The results show impedance between electrodes decreases with
      increase in the percentage of filled wells with cells and drops to a minimum
      after lysis. Impedance monitoring provides a reasonably accurate measurement of
      cell trapping and lysis. Utilizing an all-electronic approach eliminates the need
      for bulky optical components and cameras for monitoring. 

PMID- 24315877
TI  - Application of ion-sensitive field effect transistors for ion channel screening.
AB  - Cell-based screening assays are now widely used for identifying compounds that
      serve as ion channel modulators. However, instrumentation for the automated, real
      time analysis of ion flux from clonal and primary cells is lacking. This study
      describes the initial development of an ion-sensitive field effect transistor
      (ISFET)-based screening assay for the acquisition of K(+) efflux data from cells
      cultured in multi-well plates. Silicon-based K(+)-sensitive ISFETs were tested
      for their electrical response to varying concentrations of KCl and were found to
      display a linear response relationship to KCl in the range of 10 uM-1 mM. The
      ISFETs, along with reference electrodes, were inserted into fast-flow chambers
      containing either human colonic T84 epithelial cells or U251-MG glioma cells.
      Application of the Ca(2+) ionophore A23187 (1 uM), to activate Ca(2+)-activated
      non-selective cation (NSC) channels (T84 cells) and large conductance Ca(2+)
      activated K(+) (BK) channels (U251 cells), resulted in time-dependent increases
      in the extracellular K(+) concentration ([K(+)]o) as measured with the ISFETs.
      Treatment of the cells with blockers of either the NSC or BK channels, caused a
      strong inhibition of the A23187-induced increase in [K(+)]o. These results were
      consistent with ion current measurements obtained using the whole-cell
      arrangement of the patch clamp procedure. In addition, K(+) efflux data could be
      acquired in parallel from multiple cell chambers using the ISFET sensors. Given
      the non-invasive properties of the probes, the ISFET-based assay should be
      adaptable for screening ion channels in various cell types.

PMID- 24315879
TI  - High-sensitivity paracetamol sensor based on Pd/graphene oxide nanocomposite as
      an enhanced electrochemical sensing platform.
AB  - Well-dispersed Pd nanoparticles were facilely anchored on graphene oxide (Pd/GO)
      via a one-pot chemical reduction of the Pd(2+) precursor without any surfactants
      and templates. The morphology and composition of the Pd/GO nanocomposite were
      characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and energy
      dispersive analysis of X-ray (EDX). The stepwise fabrication process of the Pd/GO
      modified electrode and its electrochemical sensing performance towards
      paracetamol was evaluated using electrochemical impedance spectroscopy (EIS),
      cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The
      experimental results indicate that the as-synthesized Pd nanoparticles are
      relatively uniform in size (5-10 nm) without large aggregation and uniformly
      distributed in the carbon matrix with the overall Pd content of 28.77 wt% in
      Pd/GO. Compared with the GO modified electrode, the Pd/GO modified electrode
      shows a better electrocatalytic activity to the oxidation of paracetamol with
      lower oxidation potential and larger peak current, so the Pd/GO nanocomposite can
      be used as an enhanced sensing platform for the electrochemical determination of
      paracetamol. The kinetic parameters of the paracetamol electro-oxidation at Pd/GO
      electrode were studied in detail, and the determination conditions were
      optimized. Under the optimal conditions, the oxidation peak current is linear to
      the paracetamol concentration in the ranges of 0.005-0.5 MUM and 0.5-80.0 MUM
      with a detection limit of 2.2 nM. Based on the high sensitivity and good
      selectivity of the Pd/GO modified electrode, the proposed method was successfully
      applied to the determination of paracetamol in commercial tablets and human
      urines, and the satisfactory results confirm the applicability of this sensor in
      practical analysis.

PMID- 24315880
TI  - An in vitro study into the accuracy of a novel method for recording the
      mandibular transverse horizontal axis.
AB  - OBJECTIVES: To assess the accuracy of a novel, non-invasive method for
      determining the axis of rotation of articulated dental study casts. METHOD: A 3D
      structured light scanner was constructed using a projector and two CMOS cameras.
      Dental stone casts were arbitrarily mounted on an average value articulator. With
      the teeth together, sets of 10 scans were taken from three different viewpoints.
      Each scan captured approximately six upper teeth and six lower teeth. The teeth
      were then propped open, creating 10mm of incisal separation, and the three sets
      of 10 scans were repeated. From each pair of scans an axis of rotation was
      calculated using custom software. A total of 900 axes were created this way. The
      locations of these axes were plotted in sagittal planes located 57.5mm left and
      right of the midline to represent the position of the temporo-mandibular joints
      (TMJs). The accuracy of axis location was then assessed. RESULTS: The average
      radius of error of the individual axes, compared to the real axis, was 2.65 +/-
      1.01 mm. 61.3% of the axes lay within 3mm of the true axis, and 99.2% of the axes
      lay within 5mm of the true axis. CONCLUSIONS: The accuracy of this method is
      clinically acceptable. Further studies are required to confirm the accuracy of
      the virtual inter-occlusal records at the level of the dentition. Clinical
      studies are then indicated to determine whether the transverse horizontal axis on
      a patient can similarly be determined.

PMID- 24315881
TI  - Polypectomy rate: a surrogate for adenoma detection rate varies by colon segment,
      gender, and endoscopist.
AB  - BACKGROUND & AIMS: The adenoma detection rate (ADR) is an important measure of
      the quality of colonoscopy; it is associated with interval colorectal cancer and
      varies among sexes and locations. Recommended indicators of competence for
      colonoscopy include minimal ADRs >25% for average-risk men and >15% for women.
      These ADRs are rigorous, so polypectomy detection rate (PR) has been suggested as
      a surrogate. Colonoscopy is less effective in the proximal colon, where interval
      cancers are more likely to occur. We compared ADRs and PRs in different segments
      of colon and between sexes. METHODS: We performed a cross-sectional review of
      findings from 2167 screening colonoscopies performed by 65 endoscopists on
      average-risk outpatients at the Cleveland Clinic, 2008-2009. We reviewed
      colonoscopy and pathology reports of randomly selected procedures (mean, 33 +/-
      16 procedures per endoscopist). We calculated PRs, ADRs, and correlation between
      PR and ADR for each colon segment and sex. RESULTS: The mean overall PR was 42%
      +/- 16.7%, and ADR was 25% +/- 3.3%. The correlation between overall ADR and PR
      was strong (r = 0.80). PR of 40% in men and 30% in women correlated with the
      established minimum benchmark ADRs of 25% and 15% for men and women,
      respectively. PR was more strongly correlated with ADR in the proximal colon (r =
      0.92) than the distal colon (r = 0.58). The correlation was stronger in men than
      in women, as well as in the entire colon (r = 0.88 vs 0.75), the proximal colon
      (r = 0.91 vs 0.87), and the distal colon (r = 0.75 vs 0.55). The advanced ADR was
      4% and did not correlate with PR (r = 0.32). CONCLUSIONS: On the basis of a
      review of findings from screening colonoscopies, overall PR correlates with ADR
      for the entire colon, but PR and ADR correlate most strongly for the proximal
      colon, where many adenomas can be missed and interval cancers develop. The
      correlation between PR and ADR is weaker for women than men and for distal colon.
      If PR is used as a surrogate for ADR, colon location and patient sex should be
      considered.

PMID- 24315883
TI  - Parent and provider perspectives on immunization: are providers overestimating
      parental concerns?
AB  - OBJECTIVES: Data are limited on whether providers understand parental attitudes
      to recommended childhood immunizations. We determined parental attitudes and
      assessed how accurately providers estimated parental opinions. METHODS: Survey of
      parents and providers (pediatricians, nurses, medical assistants) in randomly
      selected practices in Houston, Texas. Surveys assessed demographics, perceptions
      of immunization importance, safety and efficacy, and acceptability of vaccine
      delivery. Providers estimated parental responses. RESULTS: 401 parents (82%
      mothers, 12% fathers, 6% other) and 105 providers participated. Parents thought
      vaccines were important for health (median score 9.5; 0=not important,
      10=extremely important) but also were concerned regarding vaccine safety and side
      effects (8.9 on 0-10 scale). 309 (77%) agreed that vaccines effectively prevent
      disease. Route of administration mattered to 147 (37%), who preferred injection
      (9.0) over oral (7.3) or intranasal (4.8) routes. Although parents would prefer
      three or fewer injections per visit, preventing more diseases (189 [47.6%]) was
      more important than number of injections (167 [42.3%]) when deciding the number
      of vaccines allowed per visit. White parents rated vaccines less important in
      preventing some illnesses than did non-white (P<=0.006 for meningitis, hepatitis,
      HPV, influenza and rotavirus) and rated number of injections per visit more
      important than number of diseases prevented (51.6% white versus 34.2% non-white;
      P 0.002). Providers underestimated parental attitudes toward vaccine importance
      (particularly influenza and HPV), and overestimated the proportion of parents who
      thought route of administration mattered (63%) and that number of injections per
      visit was the most important factor (76%) around parental vaccine decisions
      (P<0.001 for parent-provider mismatch). CONCLUSIONS: Most surveyed parents
      believe vaccines are important for child health and rate disease prevention
      higher than number of injections entailed. Providers underestimate the importance
      of some vaccines to parents and overestimate parental concerns regarding route of
      administration. Future research should focus on how this mismatch impacts
      parental vaccine decisions.

PMID- 24315882
TI  - Effect of ramosetron on stool consistency in male patients with irritable bowel
      syndrome with diarrhea.
AB  - BACKGROUND & AIMS: Ramosetron, a serotonin (5-hydroxytryptamine)-3 receptor
      antagonist with high selectivity, reduced stress-induced diarrhea and defecation
      caused by corticotropin-releasing hormone in rats. However, there have been no
      clinical trials of its effect in patients with diarrhea and irritable bowel
      syndrome (IBS-D). We performed a randomized, double-blind, placebo-controlled
      trial to determine whether ramosetron reduces diarrhea in these patients.
      METHODS: Our study included 296 male outpatients with IBS-D treated at 52 centers
      in Japan. Patients were given 5 MUg oral ramosetron (n = 147) or placebo (n =
      149) once daily for 12 weeks after a 1-week baseline period. The primary end
      point was increased stool consistency in the first month. Secondary end points
      included relief of overall IBS symptoms and increased IBS-related quality of
      life. RESULTS: More patients given ramosetron (74, 50.3%) than those given
      placebo (29, 19.6%) reported improved stool consistency in the first month (P <
      .001). The relative risk and number needed to treat were 2.57 (95% confidence
      interval, 1.79-3.70) and 3.25 (95% confidence interval, 2.44-4.89), respectively.
      The ramosetron group had significantly higher monthly rates of relief of overall
      IBS symptoms and IBS-related quality of life than the placebo group. CONCLUSIONS:
      Ramosetron (5 MUg oral, once daily for 12 weeks) improved stool consistency in
      male patients with IBS-D, compared with placebo. These study results, along with
      the pharmacologic profile of ramosetron, indicate that increased stool
      consistency is the best end point for studies of ramosetron in patients with IBS
      D. Clinicaltrials.gov No, NCT01225237.

PMID- 24315884
TI  - Routine childhood vaccination programme coverage, El Salvador, 2011-In search of
      timeliness.
AB  - While assessing immunization programmes, not only vaccination coverage is
      important, but also timely receipt of vaccines. We estimated both vaccination
      coverage and timeliness, as well as reasons for non-vaccination, and identified
      predictors of delayed or missed vaccination, for vaccines of the first two years
      of age, in El Salvador. We conducted a cluster survey among children aged 23-59
      months. Caregivers were interviewed about the child immunization status and their
      attitudes towards immunization. Vaccination dates were obtained from children
      immunization cards at home or at health facilities. We referred to the 2006
      vaccination schedule for children below two years: one dose of BCG (Bacillus
      Calmette-Guerin) at birth; rotavirus at two and four months; three doses of
      pentavalent - DTP (diphtheria-tetanus-pertussis), hepatitis B, and Haemophilus
      influenzae type b (Hib) - and of oral poliomyelitis vaccine (polio) at two, four,
      and six months; first MMR (measles-mumps-rubella) at 12 months; and first
      boosters of DTP and OPV at 18 months. Timeliness was assessed with Kaplan-Meier
      analysis; Cox and logistic regression were used to identify predictors of
      vaccination. We surveyed 2550 children. Coverage was highest for BCG (991%; 95%
      CI: 98.8-99.5) and lowest for rotavirus, especially second dose (86.3%; 95% CI:
      84.2-88.4). The first doses of MMR and DTP had 991% (95% CI: 98.5-99.6) and 977%
      (95% CI: 970-985), respectively. Overall coverage was 837% (95% CI: 81.4-86.0);
      96.4% (95% CI: 95.4-97.5), excluding rotavirus. However, only 26.7% (95% CI: 24.7
      28.8) were vaccinated within the age interval recommended by the Expanded
      Programme on Immunization. Being employed and using the bus for transport to the
      health facility were associated with age-inappropriate vaccinations; while living
      in households with only two residents and in the "Paracentral", "Occidental", and
      "Oriental" regions was associated with age-appropriate vaccinations. Vaccination
      coverage was high in El Salvador, but general timeliness and rotavirus uptake
      could be improved. 

PMID- 24315887
TI  - Thoracoscopic vs open lobectomy in infants and young children with congenital
      lung malformations.
AB  - BACKGROUND: Although thoracoscopic lobectomy is a widely accepted surgical
      procedure in adult thoracic surgery, its role in small children remains
      controversial. The purpose of this study was to evaluate perioperative outcomes
      after thoracoscopic and open lobectomy in infants and young children with
      congenital lung malformations at a single academic referral center. STUDY DESIGN:
      A cohort study of 62 consecutive children who underwent elective pulmonary
      lobectomy for a congenital lung lesion between 2001 and 2013 was performed.
      Patient demographics and perioperative outcomes were evaluated in univariate and
      logistic regression analyses. RESULTS: Forty-nine patients underwent thoracoscopy
      and 13 had a thoracotomy. Six children undergoing thoracoscopy required
      conversion to thoracotomy (conversion 12.2%). Perioperative outcomes, including
      median blood loss (2.0 vs 1.1 mL/kg; p = 0.34), chest tube duration (3 vs 3 days;
      p = 0.33), hospital length of stay (3 vs 3 days; p = 0.42), and morbidity as
      defined by the Accordion Grading Scale (30.6% vs 30.8%; p = 0.73), were similar
      between thoracoscopy and thoracotomy, respectively. Although thoracoscopy was
      associated with increased operative duration compared with thoracotomy (239.9 vs
      181.2 minutes, respectively; p = 0.03), thoracoscopy operative times decreased
      with increasing institutional experience (p = 0.048). Thoracoscopic lobectomy
      infants younger than 5 months of age had a 2.5-fold higher rate of perioperative
      adverse outcomes compared with older children (p = 0.048). CONCLUSIONS: In small
      children undergoing pulmonary lobectomy, both thoracoscopy and thoracotomy are
      associated with similar perioperative outcomes. The cosmetic and musculoskeletal
      benefits of the thoracoscopic approach must be balanced against institutional
      expertise and a potentially higher risk for complications in younger patients.

PMID- 24315885
TI  - Effects of resident involvement on complication rates after laparoscopic gastric
      bypass.
AB  - BACKGROUND: Although resident involvement has been shown to be safe for most
      procedures, the impact of residents on outcomes after complex laparoscopic
      procedures is not well understood. We sought to examine the impact of resident
      involvement on outcomes after bariatric surgery using a population-based clinical
      registry. STUDY DESIGN: We analyzed 17,057 patients who underwent a primary
      laparoscopic gastric bypass in the 35-hospital Michigan Bariatric Surgery
      Collaborative from July 2006 to August 2012. Resident involvement was
      characterized at the surgeon level. Using hierarchical logistic regression, we
      examined the influence of resident involvement on 30-day complications,
      accounting for patient characteristics as well as hospital and surgeon case
      volume. To evaluate potential mediating factors for specific complications, we
      also adjusted for operative duration. RESULTS: Risk-adjusted 30-day complication
      rates with and without residents were 13.0% and 8.5%, respectively (p < 0.01).
      Resident involvement was independently associated with wound infection (odds
      ratio [OR] = 2.06; 95% CI, 1.24-3.43) and venous thromboembolism (OR = 2.01; 95%
      CI, 1.19-3.40), but not with any other medical or surgical complications.
      Operative duration was longer with resident involvement (median duration with
      residents 129 minutes vs 88 minutes without; p < 0.01). After adjusting for
      operative duration, resident involvement was still independently associated with
      wound infection (OR = 1.67; 95% CI, 1.01-2.76), but not venous thromboembolism
      (OR = 1.73; 95% CI, 0.99-3.04). CONCLUSIONS: Resident involvement in laparoscopic
      gastric bypass is independently associated with wound infections and venous
      thromboembolism. The effect appears to be mediated in part by longer operative
      times. These findings highlight the importance of strategies to assess and
      improve resident technical proficiency outside the operating room.

PMID- 24315888
TI  - Evaluation of resistance as a measure of successful tumor ablation during
      irreversible electroporation of the pancreas.
AB  - BACKGROUND: Intraoperative evaluation of successful pancreatic tumor ablation
      using irreversible electroporation (IRE) is difficult secondary to lack of visual
      confirmation. The IRE generator provides feedback by reporting current
      (amperage), which can be used to calculate changes in tumor tissue resistance.
      The purpose of the study was to determine if resistance can be used to predict
      successful tumor ablation during IRE for pancreatic cancers. STUDY DESIGN: All
      patients undergoing pancreatic IRE from March 2010 to December 2012 were
      evaluated using a prospective database. Intraoperative information, including
      change in tumor resistance during ablation and slope of the resistance curve,
      were used to evaluate effectiveness of tumor ablation in terms of local failure
      or recurrence (LFR) and disease-free survival (DFS). RESULTS: A total of 65
      patients underwent IRE for locally advanced pancreatic cancer. Median follow-up
      was 23 months. Local failure or recurrence was seen in 17 patients at 3, 6, or 9
      months post IRE. Change in tumor tissue resistance and the slope of the
      resistance curve were both significant in predicting LFR (p = 0.02 and p = 0.01,
      respectively). The median local disease-free survival was 5.5 months in patients
      who had recurrence compared with 12.6 months in patients who did not recur (p =
      0.03). Neither mean change in tumor tissue resistance nor the slope of the
      resistance curve significantly predicted overall DFS. CONCLUSIONS: Mean change in
      tumor tissue resistance and the slope of the resistance curve could be used
      intraoperatively to assess successful tumor ablation during IRE. Larger sample
      size and longer follow-up are needed to determine if these parameters can be used
      to predict DFS.

PMID- 24315886
TI  - Treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma:
      a national perspective.
AB  - BACKGROUND: Surgery remains the only potentially curative option for patients
      with hepatocellular carcinoma (HCC) and fibrolamellar carcinoma (FLC). We sought
      to investigate the differences over time in surgically managed FLC compared with
      conventional HCC using population-based data. STUDY DESIGN: Using SEER data, we
      identified 7,225 patients with surgically managed FLC or HCC from 1986 to 2008.
      We examined differences in clinicopathologic and surgical factors associated with
      long-term survival. RESULTS: Of the 7,225 patients, the majority had HCC (n =
      7,135; 99%) vs FLC (n = 90; 1%). Patients with FLC were younger (25 years vs 59
      years) and more often were women (44% vs 27%) than patients with HCC (both p <
      0.001). Regional disease was more common among patients with FLC (42.2%) vs
      patients with HCC (22.1%) (p < 0.001). More than one-third of patients with FLC
      (36.9%) were operatively managed with a hemihepatectomy compared with patients
      with HCC, who were more often managed with a liver transplant (p < 0.001). On
      univariable analysis, there was a marked difference in overall survival, with
      patients with FLC surviving a median of 75 months vs 43 months for HCC (hazard
      ratio [HR]: 0.59; p = 0.001). There was a marked difference in survival when
      patients were stratified by localized (FLC, 78 months vs HCC, 49 months; p =
      0.012) vs regional disease (FLC, 46 months vs HCC, 23 months; p = 0.002.
      CONCLUSIONS: Patients with FLC have many clinicopathologic features that are
      different from those of patients with HCC, including younger age and female sex.
      Despite a higher likelihood of advanced disease at the time of diagnosis,
      surgically treated FLC patients had better long-term outcomes than patients with
      conventional HCC.

PMID- 24315889
TI  - Bridging the gap from T to K: integrated surgical research fellowship for the
      next generation of surgical scientists.

PMID- 24315890
TI  - Predictors of outcomes in patients with primary retroperitoneal dedifferentiated
      liposarcoma undergoing surgery.
AB  - BACKGROUND: Although sarcoma histology is recognized as a prognostic factor, most
      studies of retroperitoneal sarcomas report results combining multiple histologies
      and are inadequately powered to identify prognostic factors specific to a
      particular histology. We reviewed our experience with retroperitoneal
      dedifferentiated liposarcoma (RP DDLPS) to identify factors predictive of
      outcomes. STUDY DESIGN: All patients with RP DDLPS treated at our institution
      between 1998 and 2008 were reviewed. Multivariable Cox regression analyses were
      performed to identify factors predictive of progression-free survival (PFS),
      local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS),
      and overall survival (OS). RESULTS: We identified 119 patients with primary
      DDLPS. Median tumor size was 20.5 cm; 21% were multifocal. French Federation of
      Cancer Centers Sarcoma Group tumor grades were intermediate in 53% of patients
      and high in 28% (unknown 19%). Resections were complete (R0/R1) in 80% of
      patients and incomplete (R2) in 11% (unknown 9%). Tumors were removed intact in
      72% of patients and fragmented in 16% (unknown 12%). Median follow-up was 74.1
      months. One hundred patients (84%) experienced recurrence or progression, with
      92% occurring in the retroperitoneum. Median PFS, LRFS, DRFS, and OS were 21.1,
      21.5, 45.8, and 59.0 months, respectively, and were significantly worse with R2
      resection. On multivariate analysis, tumor integrity (intact vs fragmented) was
      predictive of PFS, multifocality predicted LRFS, and extent of resection (R0/R1
      vs R2), grade, and tumor integrity predicted OS. CONCLUSIONS: In this cohort of
      primary RP DDLPS, factors under surgeon control (tumor integrity, extent of
      resection) and reflective of tumor biology (grade, multifocality) impact patient
      outcomes.

PMID- 24315891
TI  - Validation of the Surgical Apgar Score in a veteran population undergoing general
      surgery.
AB  - BACKGROUND: The Surgical Apgar Score (SAS, a 10-point score calculated using
      limited intraoperative data) can correlate with postoperative morbidity and
      mortality after general surgery. We evaluated reliability of SAS in a veteran
      population. STUDY DESIGN: We prospectively collected demographics, medical
      history, type of surgery, and postoperative outcomes for any veteran undergoing
      general surgery at our institution (2006-2011). We categorized patients in 4 SAS
      groups and compared differences in morbidity and mortality. RESULTS: Our study
      population included 2,125 patients (SAS <=4: n = 29; SAS 5-6: n = 227; SAS 7-8: n
      = 797; SAS 9-10: n = 1,072). Low-SAS patients were likely to have significant
      preoperative comorbidities and to undergo major surgery, and had increased
      postoperative morbidity and 30-day mortality. CONCLUSIONS: The SAS is easily
      calculated from 3 routinely available intraoperative measurements, correlates
      with fixed preoperative risk (acute conditions, pre-existing comorbidities,
      operative complexity), and effectively identifies veterans at high risk for
      postoperative complications.

PMID- 24315892
TI  - Incidence, treatment, and outcomes of iron deficiency after laparoscopic Roux-en
      Y gastric bypass: a 10-year analysis.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) can lead to iron
      malabsorption through exclusion of the duodenum and proximal jejunum, decreased
      gastric acidity, and modified diet. Intravenous (IV) iron is a treatment for
      severe iron deficiency, but the incidence of iron deficiency and the frequency of
      treatment with IV iron after LRYGB are largely unknown. Our objective was to
      determine the incidence of iron deficiency and the frequency of IV iron
      administration after LRYGB. STUDY DESIGN: After obtaining IRB approval, the
      medical records of patients who underwent LRYGB from September 2001 to December
      2011 were retrospectively reviewed. Inclusion criteria consisted of determination
      of at least 1 ferritin value after surgery. Patients were grouped by level of
      iron deficiency. Patients with at least 1 ferritin <50 ng/mL were considered iron
      deficient. Statistical analysis included ANOVA. RESULTS: There were 959 patients
      included; 84.9% were female. Mean age was 43.8 years, and preoperative body mass
      index was 47.4 kg/m(2). Four hundred ninety-two (51.3%) patients were iron
      deficient. Of these, 40.9% were severely iron deficient, with a ferritin <30
      ng/mL. Intravenous iron was required by 6.7%. After IV iron therapy, 53% had
      improvement in hemoglobin and ferritin values, and 39% had improvement in
      ferritin values only. CONCLUSIONS: Given the incidence of iron deficiency after
      LRYGB observed in our series, patients should have iron status monitored
      carefully by all providers and be appropriately referred for treatment. Female
      patients should be counseled that there is a 50% chance they will become iron
      deficient after LRYGB.

PMID- 24315893
TI  - Contrast-enhanced intraoperative ultrasonic cholangiography for real-time biliary
      navigation in hepatobiliary surgery.

PMID- 24315895
TI  - Percutaneous interventional therapies for the treatment of patients with severe
      pulmonary hypertension.
AB  - Despite improvements in medical therapy, the overall prognosis of patients with
      severe pulmonary arterial hypertension remains poor. Heart-lung transplantation
      or bilateral lung transplantation is the final pathway for a minority. This paper
      describes both established and novel percutaneous interventional techniques that
      may palliate or bridge pulmonary hypertension patients to transplantation. 

PMID- 24315894
TI  - Factors associated with major bleeding events: insights from the ROCKET AF trial
      (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K
      antagonism for prevention of stroke and embolism trial in atrial fibrillation).
AB  - OBJECTIVES: This study sought to report additional safety results from the ROCKET
      AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin
      K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).
      BACKGROUND: The ROCKET AF trial demonstrated similar risks of stroke/systemic
      embolism and major/nonmajor clinically relevant bleeding (principal safety
      endpoint) with rivaroxaban and warfarin. METHODS: The risk of the principal
      safety and component bleeding endpoints with rivaroxaban versus warfarin were
      compared, and factors associated with major bleeding were examined in a
      multivariable model. RESULTS: The principal safety endpoint was similar in the
      rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard
      ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk
      increased with age, but there were no differences between treatments in each age
      category (<65, 65 to 74, >=75 years; pinteraction = 0.59). Compared with those
      without (n = 13,455), patients with a major bleed (n = 781) were more likely to
      be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild
      anemia, and a lower calculated creatinine clearance and less likely to be female
      or have a prior stroke/transient ischemic attack. Increasing age, baseline
      diastolic blood pressure (DBP) >=90 mm Hg, history of chronic obstructive
      pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were
      independently associated with major bleeding risk; female sex and DBP <90 mm Hg
      were associated with a decreased risk. CONCLUSIONS: Rivaroxaban and warfarin had
      similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP,
      prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated
      with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban
      With Warfarin for the Prevention of Stroke and Non-Central Nervous System
      Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation:
      NCT00403767).

PMID- 24315896
TI  - Endpoints for diuresis: are we there yet?

PMID- 24315897
TI  - Incidence of sudden cardiac arrest in Minnesota high school student athletes: the
      limitations of catastrophic insurance claims.

PMID- 24315898
TI  - Ankle-brachial index in patients with nonvalvular atrial fibrillation.

PMID- 24315899
TI  - The individualized obesity paradox.

PMID- 24315900
TI  - New insights on plaque erosion and calcified nodules: "seeing is believing".

PMID- 24315901
TI  - Therapeutic drug monitoring facilitates blood pressure control in resistant
      hypertension.

PMID- 24315902
TI  - Cardiac hepatopathy versus end-stage liver disease: two different entities.

PMID- 24315903
TI  - Double-chambered right ventricle and bicuspid pulmonic valve: a thrilling
      discovery.

PMID- 24315904
TI  - Reply: cardiac hepatopathy versus end-stage liver disease: two different
      entities.

PMID- 24315905
TI  - Reply: ankle-brachial index in patients with nonvalvular atrial fibrillation.

PMID- 24315906
TI  - Body mass index and mortality in acutely decompensated heart failure across the
      world: a global obesity paradox.
AB  - OBJECTIVES: This study sought to define the relationship between body mass index
      (BMI) and mortality in heart failure (HF) across the world and to identify
      specific groups in whom BMI may differentially mediate risk. BACKGROUND: Obesity
      is associated with incident HF, but it is paradoxically associated with better
      prognosis during chronic HF. METHODS: We studied 6,142 patients with acute
      decompensated HF from 12 prospective observational cohorts followed-up across 4
      continents. Primary outcome was all-cause mortality. Cox proportional hazards
      models and net reclassification index described associations of BMI with all
      cause mortality. RESULTS: Normal-weight patients (BMI 18.5 to 25 kg/m(2)) were
      older with more advanced HF and lower cardiometabolic risk. Despite worldwide
      heterogeneity in clinical features across obesity categories, a higher BMI
      remained associated with decreased 30-day and 1-year mortality (11% decrease at
      30 days; 9% decrease at 1 year per 5 kg/m(2); p < 0.05), after adjustment for
      clinical risk. The BMI obtained at index admission provided effective 1-year risk
      reclassification beyond current markers of clinical risk (net reclassification
      index 0.119, p < 0.001). Notably, the "protective" association of BMI with
      mortality was confined to persons with older age (>75 years; hazard ratio [HR]:
      0.82; p = 0.006), decreased cardiac function (ejection fraction <50%; HR: 0.85; p
      < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p =
      0.004). CONCLUSIONS: A lower BMI is associated with age, disease severity, and a
      higher risk of death in acute decompensated HF. The "obesity paradox" is confined
      to older persons, with decreased cardiac function, less cardiometabolic illness,
      and recent-onset HF, suggesting that aging, HF severity/chronicity, and
      metabolism may explain the obesity paradox.

PMID- 24315907
TI  - Morphine decreases clopidogrel concentrations and effects: a randomized, double
      blind, placebo-controlled trial.
AB  - OBJECTIVES: This study sought to examine the possible drug-drug interactions
      between clopidogrel and morphine. BACKGROUND: Because morphine-the recommended
      treatment for pain of myocardial infarction-is associated with poor clinical
      outcome, we hypothesized that morphine lowers the plasma levels of clopidogrel
      active metabolite as well as its effects on platelets. METHODS: Twenty-four
      healthy subjects received a loading dose of 600 mg clopidogrel together with
      placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo
      controlled, cross-over trial. Pharmacokinetics was determined by liquid
      chromatography tandem mass spectrometry, and clopidogrel effects were measured by
      platelet function tests. RESULTS: Morphine injection delayed clopidogrel
      absorption (p = 0.025) and reduced the area under the curve levels of its active
      metabolite by 34% (p = 0.001). Morphine delayed the maximal inhibition of
      platelet aggregation on average by 2 h (n = 24; p < 0.001). Residual platelet
      aggregation was higher 1 to 4 h after morphine injection (n = 24; p < 0.005).
      Furthermore, morphine delayed the inhibition of platelet plug formation under
      high shear rates (P2Y-Innovance; n = 21; p < 0.004) and abolished the 3-fold
      prolongation in collagen adenosine diphosphate-induced closure times seen in
      extensive and rapid metabolizers (n = 16; p = 0.001). CONCLUSIONS: Morphine
      delays clopidogrel absorption, decreases plasma levels of clopidogrel active
      metabolite, and retards and diminishes its effects, which can lead to treatment
      failure in susceptible individuals. (Drug/Drug Interactions of Aspirin and P2Y12
      inhibitors; NCT01369186).

PMID- 24315908
TI  - PAD is no longer related to Rodney: the benefit of statins.

PMID- 24315909
TI  - Subclinical abnormalities in sarcoplasmic reticulum Ca(2+) release promote
      eccentric myocardial remodeling and pump failure death in response to pressure
      overload.
AB  - OBJECTIVES: This study sought to explore whether subclinical alterations of
      sarcoplasmic reticulum (SR) Ca(2+) release through cardiac ryanodine receptors
      (RyR2) aggravate cardiac remodeling in mice carrying a human RyR2(R4496C+/-) gain
      of-function mutation in response to pressure overload. BACKGROUND: RyR2
      dysfunction causes increased diastolic SR Ca(2+) release associated with
      arrhythmias and contractile dysfunction in inherited and acquired cardiac
      diseases, such as catecholaminergic polymorphic ventricular tachycardia and heart
      failure (HF). METHODS: Functional and structural properties of wild-type and
      catecholaminergic polymorphic ventricular tachycardia-associated RyR2(R4496C+/-)
      hearts were characterized under conditions of pressure overload induced by
      transverse aortic constriction (TAC). RESULTS: Wild-type and RyR2(R4496C+/-)
      hearts had comparable structural and functional properties at baseline. After
      TAC, RyR2(R4496C+/-) hearts responded with eccentric hypertrophy, substantial
      fibrosis, ventricular dilation, and reduced fractional shortening, ultimately
      resulting in overt HF. RyR2(R4496C+/-)-TAC cardiomyocytes showed increased
      incidence of spontaneous SR Ca(2+) release events, reduced Ca(2+) transient peak
      amplitude, and SR Ca(2+) content as well as reduced SR Ca(2+)-ATPase 2a and
      increased Na(+)/Ca(2+)-exchanger protein expression. HF phenotype in
      RyR2(R4496C+/-)-TAC mice was associated with increased mortality due to pump
      failure but not tachyarrhythmic events. RyR2-stabilizer K201 markedly reduced
      Ca(2+) spark frequency in RyR2(R4496C+/-)-TAC cardiomyocytes. Mini-osmotic pump
      infusion of K201 prevented deleterious remodeling and improved survival in
      RyR2(R4496C+/-)-TAC mice. CONCLUSIONS: The combination of subclinical congenital
      alteration of SR Ca(2+) release and pressure overload promoted eccentric
      remodeling and HF death in RyR2(R4496C+/-) mice, and pharmacological RyR2
      stabilization prevented this deleterious interaction. These findings suggest
      potential clinical relevance for patients with acquired or inherited gain-of
      function of RyR2-mediated SR Ca(2+) release.

PMID- 24315910
TI  - Does a ripple of Ca(2+) leak develop into a rogue wave that can trigger
      pathological hypertrophy?

PMID- 24315912
TI  - Reply: is the J wave or the ST slope malignant...or neither?

PMID- 24315911
TI  - Association between statin medications and mortality, major adverse
      cardiovascular event, and amputation-free survival in patients with critical limb
      ischemia.
AB  - OBJECTIVES: The aim of this study was to determine the associations between
      statin use and major adverse cardiovascular and cerebrovascular events (MACCE)
      and amputation-free survival in critical limb ischemia (CLI) patients.
      BACKGROUND: CLI is an advanced form of peripheral arterial disease associated
      with nonhealing arterial ulcers and high rates of MACCE and major amputation.
      Although statin medications are recommended for secondary prevention in
      peripheral arterial disease, their effectiveness in CLI is uncertain. METHODS: We
      reviewed 380 CLI patients who underwent diagnostic angiography or therapeutic
      endovascular intervention from 2006 through 2012. Propensity scores and inverse
      probability of treatment weighting were used to adjust for baseline differences
      between patients taking and not taking statins. RESULTS: Statins were prescribed
      for 246 (65%) patients. The mean serum low-density lipoprotein (LDL) level was
      lower in patients prescribed statins (75 +/- 28 mg/dl vs. 96 +/- 40 mg/dl, p <
      0.001). Patients prescribed statins had more baseline comorbidities including
      diabetes, coronary artery disease, and hypertension, as well as more extensive
      lower extremity disease (all p values <0.05). After propensity weighting, statin
      therapy was associated with lower 1-year rates of MACCE (stroke, myocardial
      infarction, or death; hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.28
      to 0.99), mortality (HR: 0.49, 95% CI: 0.24 to 0.97), and major amputation or
      death (HR: 0.53, 95% CI: 0.35 to 0.98). Statin use was also associated with
      improved lesion patency among patients undergoing infrapopliteal angioplasty.
      Patients with LDL levels >130 mg/dl had increased HRs of MACCE and mortality
      compared with patients with lower levels of LDL. CONCLUSIONS: Statins are
      associated with lower rates of mortality and MACCE and increased amputation-free
      survival in CLI patients.

PMID- 24315913
TI  - Reply: Prognostic significance of patients with vasospastic angina.

PMID- 24315914
TI  - Prognostic stratification of patients with vasospastic angina.

PMID- 24315915
TI  - Effects of heparin on temporal microRNA profiles.

PMID- 24315916
TI  - Renal denervation and left ventricular mass regression: a benefit beyond blood
      pressure reduction?

PMID- 24315917
TI  - Reply: effects of heparin on temporal microRNA profiles.

PMID- 24315918
TI  - Limits of Mendelian randomization analyses in selection of secretory
      phospholipase A2-IIA as a valid therapeutic target for prevention of
      cardiovascular disease.

PMID- 24315919
TI  - Improvements in left ventricular hypertrophy and diastolic function following
      renal denervation: effects beyond blood pressure and heart rate reduction.
AB  - OBJECTIVES: This study sought to investigate the interaction between blood
      pressure (BP) and heart rate (HR) reduction and changes in left ventricular (LV)
      structure and function following renal sympathetic denervation (RDN). BACKGROUND:
      Hypertension results in structural and functional cardiac changes. RDN reduces
      BP, HR, and LV mass and improves diastolic dysfunction. METHODS: We evaluated LV
      size, mass, and function before and 6 months after RDN in 66 patients with
      resistant hypertension and analyzed results in relation to systolic BP (SBP) and
      HR. RESULTS: SBP decreased by 11 +/- 3 mm Hg in the first, 18 +/- 5 mm Hg in the
      second, and 36 +/- 7 mm Hg in the third tertile of SBP at baseline (p < 0.001).
      HR decreased by 13 +/- 4 beats/min, 8 +/- 3 beats/min, and 11 +/- 6 beats/min in
      tertiles of SBP (p for interaction between tertiles = 0.314). In all SBP
      tertiles, LV mass index (LVMI) decreased similarly (LVMI -6.3 +/- 2.2 g/m(2.7), 
      8.3 +/- 2.1 g/m(2.7), and -9.6 +/- 1.9 g/m(2.7); p for interaction = 0.639). LVMI
      decreased unrelated to HR at baseline (p for interaction = 0.471). The diastolic
      parameters E-wave deceleration time, isovolumetric relaxation time, and E'-wave
      velocity improved similarly in all tertiles of SBP and HR. Changes in LV mass and
      function were also unrelated to reduction in SBP or HR. Vascular compliance
      improved dependently on BP but independently of HR reduction. CONCLUSIONS: In
      patients with resistant hypertension, LV hypertrophy and diastolic function
      improved 6 months after RDN, without significant relation to SBP and HR. These
      findings suggest a direct effect of altered sympathetic activity in addition to
      unloading on cardiac hypertrophy and function.

PMID- 24315920
TI  - Reply: limits of Mendelian randomization analyses in selection of secretory
      phospholipase A2-IIA as a valid therapeutic target for prevention of
      cardiovascular disease.

PMID- 24315921
TI  - Is the J wave or the ST slope malignant...or neither?

PMID- 24315922
TI  - Multimodality approach to rare coronary artery malformation.

PMID- 24315923
TI  - Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) -
      Pluronic((r)) F127 copolymers for controlled protein release.
AB  - Thermosensitive hydrogels are of a great interest due to their many biomedical
      and pharmaceutical applications. In this study, we synthesized a new series of
      random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez((r)) AN, GZ) and
      Pluronic((r)) F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive
      hydrogels whose gelation temperature and mechanical properties could be
      controlled by the molar ratio of GZ and PF127 polymers and the copolymer
      concentration in water. Gelation temperatures tended to decrease when the
      GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures
      decreased at higher copolymer concentrations. Moreover, these hydrogels
      controlled the release of proteins such as bovine serum albumin (BSA) and
      recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11)
      more than the PF127 system. Toxicity studies carried out in J774.2 macrophages
      showed that cell viability was higher than 80%. Finally, histopathological
      analysis revealed that subcutaneous administration of low volumes of these
      hydrogels elicited a tolerable inflammatory response that could be useful to
      induce immune responses against the protein cargo in the development of vaccine
      adjuvants. 

PMID- 24315924
TI  - Use of heat of adsorption to quantify amorphous content in milled pharmaceutical
      powders.
AB  - Isothermal calorimetry operated in gas perfusion mode (IGPC) is often used to
      quantify the amorphous content of pharmaceutical powders. Typically, the
      calibration line is constructed using the heat of crystallisation as the sample
      is exposed to high levels of a plasticising vapour. However, since the physical
      form to which the amorphous fraction crystallises may be dependent on the
      presence of any crystalline seed, the calibration line is often seen to be non
      linear, especially as the amorphous content of the sample approaches 100% w/w.
      Redesigning the experiment so that the calibration line is constructed with the
      heat of adsorption is an alternative approach that, because it is not dependent
      upon crystallisation to a physical form should ameliorate this problem. The two
      methods are compared for a model compound, salbutamol sulphate, which forms
      either a hydrate or an anhydrate depending on the amorphous content. The heat of
      adsorption method was linear between amorphous contents of 0 and 100% w/w and
      resulted in a detection limit of 0.3% w/w and a quantification limit of 0.92%
      w/w. The heat of crystallisation method was linear only between amorphous
      contents of 0 and 80% w/w and resulted in a detection limit of 1.7% w/w and a
      quantification limit of 5.28% w/w. Thus, the use of heat of adsorption is shown
      to be a better method for quantifying amorphous contents to better than 1% w/w. 

PMID- 24315925
TI  - Contextual modulation of androgen effects on agonistic interactions.
AB  - Seasonal changes in steroid hormones are known to have a major impact on social
      behavior, but often are quite sensitive to environmental context. In the bi
      directionally sex changing fish, Lythrypnus dalli, stable haremic groups exhibit
      baseline levels of interaction. Status instability follows immediately after male
      removal, causing transiently elevated agonistic interactions and increase in
      brain and systemic levels of a potent fish androgen, 11-ketotestosterone (KT).
      Coupling KT implants with a socially inhibitory environment for protogynous sex
      change induces rapid transition to male morphology, but no significant change in
      social behavior and status, which could result from systemically administered
      steroids not effectively penetrating into brain or other tissues. Here, we first
      determined the degree to which exogenously administered steroids affect the
      steroid load within tissues. Second, we examined whether coupling a social
      environment permissive to sex change would influence KT effects on agonistic
      behavior. We implanted cholesterol (Chol, control) or KT in the dominant
      individual (alpha) undergoing sex change (on d0) and determined the effects on
      behavior and the degree to which administered steroids altered the steroid load
      within tissues. During the period of social instability, there were rapid (within
      2 h), but transient effects of KT on agonistic behavior in alphas, and secondary
      effects on betas. On d3 and d5, all KT, but no Chol, treated females had male
      typical genital papillae. Despite elevated brain and systemic KT 5 days after
      implant, overall rates of aggressive behavior remained unaffected. These data
      highlight the importance of social context in mediating complex hormone-behavior
      relationships.

PMID- 24315926
TI  - Natural stimuli from three coherent modalities enhance behavioral responses and
      electrophysiological cortical activity in humans.
AB  - Cues that involve a number of sensory modalities are processed in the brain in an
      interactive multimodal manner rather than independently for each modality. We
      studied multimodal integration in a natural, yet fully controlled scene,
      implemented as an interactive game in an auditory-haptic-visual virtual
      environment. In this imitation of a natural scene, the targets of perception were
      ecologically valid uni-, bi- and tri-modal manifestations of a simple event-a
      ball hitting a wall. Subjects were engaged in the game while their behavioral and
      early cortical electrophysiological responses were measured. Behavioral results
      confirmed that tri-modal cues were detected faster and more accurately than bi
      modal cues, which, likewise, showed advantages over unimodal responses. Event
      Related Potentials (ERPs) were recorded, and the first 200 ms following stimulus
      onset was analyzed to reveal the latencies of cortical multimodal interactions as
      estimated by sLORETA. These electrophysiological findings indicated bi-modal as
      well as tri-modal interactions beginning very early (~30 ms), uniquely for each
      multimodal combination. The results suggest that early cortical multimodal
      integration accelerates cortical activity and, in turn, enhances performance
      measures. This acceleration registers on the scalp as sub-additive cortical
      activation.

PMID- 24315927
TI  - Histone extraction protocol from the two model diatoms Phaeodactylum tricornutum
      and Thalassiosira pseudonana.
AB  - Post-translational modifications of histones affect many biological processes by
      influencing higher order chromatin structure that affects gene and genome
      regulation. It is therefore important to develop methods for extracting histones
      while maintaining their native post-translational modifications. While histone
      extraction protocols have been developed in multicellular and single celled
      organisms such as yeast and Arabidopsis, they are inefficient in diatoms that
      have a silica cell wall that is likely to hinder histone extraction. We report in
      this work a rapid and reliable method for extraction of large amounts of high
      quality histones from the two model diatoms Phaeodactylum tricornutum and
      Thalassiosira pseudonana. The protocol is an important enabling step permitting
      downstream applications such as western blotting and mass spectrometry. 

PMID- 24315928
TI  - Neuronal damage, central cholinergic dysfunction and oxidative damage correlate
      with cognitive deficits in rats with chronic cerebral hypoperfusion.
AB  - Chronic cerebral hypoperfusion has been identified to be a risk factor for
      cognitive decline in aging, vascular dementia, and Alzheimer's disease.
      Substantial evidence has shown that chronic cerebral hypoperfusion may cause
      cognitive impairment, but the underlying neurobiological mechanism is poorly
      understood so far. In this study, we used a rat model of chronic cerebral
      hypoperfusion by permanent bilateral common carotid artery occlusion (BCCAO) to
      investigate the alterations of neuronal damage, glial activation oxidative stress
      and central cholinergic dysfunction, and their causal relationship with the
      cognitive deficits induced by chronic cerebral hypoperfusion. We found that BCCAO
      rats exhibited spatial learning and memory impairments and working memory
      dysfunction 12 weeks after BCCAO compared with sham-operated rats, simultaneously
      accompanied by significantly increased neuronal damage and glial cell activation
      in the cerebral cortex and hippocampus. Twelve weeks of BCCAO treatment in rats
      resulted in central cholinergic dysfunction and increased oxidative damage
      compared with sham-operated rats. Correlational analyses revealed that spatial
      learning and memory impairments and working memory dysfunction were significantly
      correlated with the measures of neuronal damage, central cholinergic dysfunction
      and oxidative damage in the cerebral cortex and hippocampus of rats with BCCAO.
      Moreover, the measures of neuronal damage and central cholinergic dysfunction
      were significantly correlated with the indexes of oxidative damage in rats with
      BCCAO. Collectively, this study provides novel evidence that neuronal damage and
      central cholinergic dysfunction is likely due to increased oxidative stress under
      the condition of chronic cerebral hypoperfusion. Furthermore, the results of the
      present study suggest that neuronal damage, central cholinergic dysfunction and
      oxidative damage in the brain following the reduction of cerebral blood flow
      could be involved in cognitive deficits induced by chronic cerebral
      hypoperfusion.

PMID- 24315929
TI  - Sex differences in stress effects on response and spatial memory formation.
AB  - Stress and stress hormones are known to affect learning and memory processes.
      However, although effects of stress on hippocampus-dependent declarative learning
      and memory are well-documented, relatively little attention has been paid to the
      impact of stress on striatum-dependent stimulus-response (S-R) learning and
      memory. Recent evidence indicates that glucocorticoid stress hormones shortly
      after learning enhance S-R memory consolidation, whereas stress prior to
      retention testing impairs S-R memory retrieval. Whether stress affects also the
      acquisition of S-R memories in humans remains unclear. For this reason, we
      examined here the effects of acute stress on S-R memory formation and contrasted
      these stress effects with those on hippocampus-dependent spatial memory. Healthy
      men and women underwent a stressor (socially evaluated cold pressor test, SECPT)
      or a control manipulation before they completed an S-R task and two spatial
      learning tasks. Memory was assessed one week later. Our data showed that stress
      impaired S-R memory performance in men but not in women. Conversely, spatial
      memory was impaired by stress in women but not in men. These findings provide
      further evidence that stress may alter learning and memory processes beyond the
      hippocampus. Moreover, our data underline that participants' sex may play a
      critical role in the impact of stress on multiple memory systems. 

PMID- 24315930
TI  - Pyrrolidine dithiocarbamate protects against scopolamine-induced cognitive
      impairment in rats.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disorder that leads to
      disturbances of cognitive functions. Although the primary cause of AD remains
      unclear, brain acetylcholine deficiency, oxidative stress and neuroinflammation
      may be considered the principal pathogenic factors. The present study was
      constructed to investigate the anti-amnestic effect of pyrrolidine
      dithiocarbamate (PDTC) on scopolamine-induced behavioral, neurochemical and
      biochemical changes in rats. PDTC (50 and 100mg/kg) and donepezil (2.5mg/kg) were
      orally administered for 14 successive days. Dementia was induced at the end of
      the treatment period by a single injection of scopolamine (20mg/kg; i.p.), and Y
      maze test was conducted 30min thereafter. Rats were then sacrificed and
      homogenates of cortical and hippocampal tissues were used for the estimation of
      noradrenaline, dopamine, serotonin and heat shock protein 70 contents along with
      acetylcholinesterase activity. In addition, certain oxidative stress markers, pro
      inflammatory and anti-inflammatory cytokines were assessed. Histological
      examination of cortical and hippocampal tissues was also performed. Scopolamine
      resulted in memory impairment that was coupled by alterations in the estimated
      neurotransmitters, heat shock protein 70, acetylcholinesterase activity,
      oxidative stress as well as inflammatory biomarkers. Histological analysis
      revealed serious damaging effects of scopolamine on the structure of cerebral
      cortex and hippocampus. Pretreatment of rats with PDTC in both doses mitigated
      scopolamine-induced behavioral, biochemical, neurochemical and histological
      changes in a manner comparable to donepezil. The observed anti-amnestic effect of
      PDTC makes it a promising candidate for clinical trials in patients with
      cognitive impairment. 

PMID- 24315931
TI  - Effect of curcumin on diabetic peripheral neuropathic pain: possible involvement
      of opioid system.
AB  - Neuropathic pain is one of the most common complications of diabetes mellitus. As
      efficacy and tolerability of current therapy for neuropathic pain are not ideal,
      we need to develop the novel drug for better treatment. Curcumin as a natural
      flavonoid from Curcuma longa has considerable effects on nervous system such as,
      antidepressant, antinociceptive and neuroprotective effects. The present study
      was designed to investigate the effect of curcumin on diabetic peripheral
      neuropathic pain and possible involvement of opioid system. A single dose of
      60mg/kg streptozotocin was injected intraperitoneally to induce diabetes in rats.
      STZ-induced diabetic rats were treated with curcumin (50mg/kg/day) acute and
      chronically. Thermal hyperalgesia and mechanical allodynia were measured on the
      days 0, 7, 14 and 21 after diabetes induction as behavioral scores of neuropathic
      pain. Chronic, but not acute, treatment with curcumin prevents the weight loss
      and attenuates mechanical allodynia in STZ-induced diabetic rats. Pretreatment
      with naloxone (1mg/kg) significantly reduced anti-allodynic effect of chronic
      curcumin in von Frey filament test. Our results suggest that curcumin can be
      considered as a new therapeutic potential for the treatment of diabetic
      neuropathic pain and the activation of opioid system may be involved in the
      antinociceptive effect of curcumin. 

PMID- 24315932
TI  - In vivo administration of ritonavir worsens intestinal damage caused by
      cyclooxygease inhibitors.
AB  - The protease inhibitor ritonavir is part of the highly active anti-retroviral
      therapy (HAART) successfully used in the treatment of human immunodeficiency
      virus (HIV)-1 infection. There is evidence that ritonavir alters intestinal
      permeability and induces damage to the small intestine. Because HIV infected
      patients taking HAART are at high risk for developing cardiovascular
      complications, there might be a need for the use of low dose of aspirin (ASA) to
      prevent ischemic events. Similarly, long term survival exposes HIV infected
      persons to detrimental interactions of ritonavir with non-steroidal anti
      inflammatory drugs (NSAIDs). In the present work we tested whether ritonavir
      worsens intestinal injury caused by NSAIDs and ASA. C57BL6 mice were treated for
      25 days with ritonavir and for a further 5 days with the combination of ritonavir
      plus ASA or ritonavir plus naproxen. In a second set of experiments C57BL6 mice
      were cotreated with ritonavir plus misoprostol, a PGE1 analog. We found that
      ritonavir administration caused intestinal damage and its co-administration with
      naproxen or ASA exacerbated the severity of injury and intestinal inflammation,
      as assessed by measuring haematocrit, MPO, mucosal levels of PGE2 and mRNA levels
      of iNOS, MCP-1 and VLA-1. Co-administration of misoprostol protected against
      intestinal damage induced by naproxen and ritonavir. In conclusion we
      demonstrated that ritonavir causes intestinal damage and that its association
      with NSAIDs or ASA worsens the damage caused by COX-inhibitors. Misoprostol
      rescues from intestinal damage caused by ritonavir. Further studies are need to
      clarify whether this observation has a clinical readout. 

PMID- 24315933
TI  - [Treatment of varicose veins and limb lymphedema].
AB  - Two questions arise when considering the treatment of varicose veins and the
      development of lymphedema: can the treatment cause lymphedema? Can it worsen it?
      Primary lymphedema is rarely associated with varicose veins except in the
      lymphedema-distichiasis syndrome. Data available in the literature is essentially
      based on surgical treatment. Stripping on a normal limb may induce chronic
      lymphedema in almost 0.1% of cases. The risk of lymphedema after stripping in
      patients with previous pelvic surgery including lymph node excision and/or
      radiotherapy remains unknown. In patients with lower limb lymphedema wearing
      strong elastic compression stockings, stripping provides little clinical
      improvement and can worsen volume. The main objective is also to avoid venous
      complications. Lymphatic lesions related to stripping can be evaluated by
      lymphography or lymphoscintigraphy. New techniques for treating varicose veins
      (sclerotherapy, endovenous laser treatment, radiofrequency ablation) seem to
      induce fewer lymphatic complications. Further studies are required to confirm
      these results. Indications for treatment should be unquestionable and patients
      must be alerted to the potential risk of lymphedema or its worsening. 

PMID- 24315935
TI  - Aging and immunity - impact of behavioral intervention.
AB  - Immune responses to pathogens to which they were not previously exposed are
      commonly less effective in elderly people than in young adults, whereas those to
      agents previously encountered and overcome in earlier life may be amplified. This
      is reflected in the robust finding in many studies that the proportions and
      numbers of naive B and T cells are lower and memory cells higher in the elderly.
      In addition to the "extrinsic" effects of pathogen exposure, "intrinsic" events
      such as age-associated differences in haematopoeitic stem cells and their niches
      in the bone marrow associated with differences in cell maturation and output to
      the periphery are also observed. In the case of T cells, the "intrinsic" process
      of thymic involution, beginning before puberty, further contributes to reducing
      the production of naive T cells. Like memory T cell populations, innate immune
      cells may be increased in number but decreased in efficacy on a per-cell basis.
      Thus, superimposed on chronological age alone, remodelling of immunity as a
      result of interactions with the environment over the life course is instrumental
      in shaping immune status in later life. In addition to interactions with
      pathogens, host microbiome and nutrition, exercise and stress, and many other
      extrinsic factors are crucial modulators of this "immunosenescence" process. In
      this review, we briefly outline the observed immune differences between younger
      and older people, and discuss the possible impacts of behavioral variations
      thereon. 

PMID- 24315936
TI  - Impact of changes in broth composition on Chlorella vulgaris cultivation in a
      membrane photobioreactor (MPBR) with permeate recycle.
AB  - A membrane photobioreactor (MPBR) is a proven and very useful concept in which
      microalgae can be simultaneously cultivated and pre-harvested. However, the
      behavior with respect to accumulation of algogenic organic matter, including
      transparent exopolymeric particles (TEPs), counter ions and unassimilated
      nutrients due to the recycling of the medium is still unclear, even though the
      understanding of this behavior is essential for the optimization of microalgae
      processing. Therefore, the dynamics of these compounds, especially TEPs, during
      coupled cultivation and harvesting of Chlorella vulgaris in an MPBR with permeate
      recycle are addressed in this study. Results show that TEPs are secreted during
      algae cell growth, and that their presence is thus inevitable. In the system with
      permeate recycle, substances such as counter ions and unassimilated nutrients get
      accumulated in the system. This was proven to limit the algae growth, together
      with the occurrence of bioflocculation due to an increasing broth pH. 

PMID- 24315934
TI  - Posttranscriptional RNA Modifications: playing metabolic games in a cell's
      chemical Legoland.
AB  - Nature combines existing biochemical building blocks, at times with subtlety of
      purpose. RNA modifications are a prime example of this, where standard RNA
      nucleosides are decorated with chemical groups and building blocks that we recall
      from our basic biochemistry lectures. The result: a wealth of chemical diversity
      whose full biological relevance has remained elusive despite being public
      knowledge for some time. Here, we highlight several modifications that, because
      of their chemical intricacy, rely on seemingly unrelated pathways to provide
      cofactors for their synthesis. Besides their immediate role in affecting RNA
      function, modifications may act as sensors and transducers of information that
      connect a cell's metabolic state to its translational output, carefully
      orchestrating a delicate balance between metabolic rate and protein synthesis at
      a system's level. 

PMID- 24315937
TI  - Application of a recyclable plastic bulking agent for sewage sludge composting.
AB  - A recyclable plastic bulking agent (RPBA) that can be screened and reused was
      developed to improve sludge composting and to reduce costs. Two RPBAs were
      developed: RPBA35 (35 mm in diameter) and RPBA50 (50mm in diameter). The
      objective was to study the influence of size and quantity of RPBA on temperature,
      oxygen content, water removal during sludge composting, and phytotoxicity of the
      compost. RPBAs of both sizes improved the temperature, oxygen supply, and water
      removal compared with the treatment with no RPBA, and obtained phytotoxic-free
      compost. RPBA50 more effectively removed water than RPBA35. Oxygen diffusion rate
      in the composting pile containing RPBA50 was higher than in the treatment with no
      RPBA. When the RPBA50: sludge mixture ratio was above 1:1.5, the period over
      which the temperature exceeded 55  degrees C was insufficient to meet the
      harmless treatment requirement. The water evaporation rate was highest at a ratio
      of 1:2.

PMID- 24315938
TI  - Mixed culture syngas fermentation and conversion of carboxylic acids into
      alcohols.
AB  - Higher alcohols such as n-butanol and n-hexanol have higher energy density than
      ethanol, are more compatible with current fuel infrastructure, and can be
      upgraded to jet and diesel fuels. Several organisms are known to convert syngas
      to ethanol, but very few can produce higher alcohols alone. As a potential
      solution, mixed culture fermentation between the syngas fermenting Alkalibaculum
      bacchi strain CP15 and propionic acid producer Clostridium propionicum was
      studied. The monoculture of CP15 produced only ethanol from syngas without
      initial addition of organic acids to the fermentation medium. However, the mixed
      culture produced ethanol, n-propanol and n-butanol from syngas. The addition of
      propionic acid, butyric acid and hexanoic acid to the mixed culture resulted in a
      50% higher conversion efficiency of these acids to their respective alcohols
      compared to CP15 monoculture. These findings illustrate the great potential of
      mixed culture syngas fermentation in production of higher alcohols. 

PMID- 24315939
TI  - Methanosarcina spp., the key to relieve the start-up of a thermophilic anaerobic
      digestion suffering from high acetic acid loads.
AB  - This paper investigates if it is possible to produce inocula to counteract high
      acetic acid (CH3COO(-)) concentrations during thermophilic anaerobic digestion.
      To this end, fermenter sludge was exposed for different durations to either
      gradually increasing CH3COO(-) concentrations or directly exposed to a high
      concentration (150 mM). Altogether, these enrichments led to inocula with a
      distinct decrease of representatives of Methanobacteriales, while those of
      Methanoculleus spp. were hardly affected by any treatment. After the inoculation,
      good agreements of the abundance of Methanosarcinales and Methanoculleus spp.
      with total DNA content and methane production rate were apparent. In addition, a
      gradual adaptation of the inoculum for at least 4 weeks led to a significant
      increase of Methanosarcina spp. during the subsequent fermentation. These results
      demonstrate the potential of bioaugmentation to relieve the start-up of an
      anaerobic digestion suffering from high CH3COO(-) loads, especially pointing to
      the robust acetoclastic genus Methanosarcina.

PMID- 24315941
TI  - Active signals, gradient formation and regional specificity in neural induction.
AB  - The question of how the vertebrate embryo gives rise to a nervous system is of
      paramount interest in developmental biology. Neural induction constitutes the
      earliest step in this process and is tightly connected with development of the
      embryonic body axes. In the Xenopus embryo, perpendicular gradients of BMP and
      Wnt signals pattern the dorsoventral and anteroposterior body axes. Both pathways
      need to be inhibited to allow anterior neural induction to occur. FGF8 and IGF
      are active neural inducers that together with BMP and Wnt signals are integrated
      at the level of Smad 1/5/8 phosphorylation. Hedgehog (Hh) also contributes to
      anterior neural induction. Suppressor-of-fused plays an important role in
      intertwining the Hh and Wnt pathways. Distinct mechanisms are discussed that
      establish morphogen gradients and integrate retinoic acid and FGF signals during
      posterior development. These findings not only improve our understanding of
      regional specification in neural induction, but have profound implications for
      mammalian stem cell research and regenerative medicine. 

PMID- 24315940
TI  - Implications of sludge liquor addition for wastewater-based open pond cultivation
      of microalgae for biofuel generation and pollutant remediation.
AB  - The growth improvement of microalgal strains in municipal secondary-treated
      wastewater by addition of nutrient-rich activated sludge centrate liquor was
      examined. Two strains (Chlorella luteoviridis and Parachlorella hussii) were
      tolerant to liquor, with addition of 25% liquor providing the best growth,
      biomass productivity and nutrient removal values. The capability of C.
      luteoviridis and P. hussii for full seasonal cultivation in a 150 L open pond in
      a temperate climate was studied, using the optimised secondary wastewater +25%
      liquor medium. Each strain was capable of growth all year including in autumn and
      winter but with strongest growth, productivity and remediation characteristics in
      the summer and spring. Both strains could maintain monoculture growth with no
      significant contamination or culture crash, demonstrating the robustness of these
      strains for wastewater cultivation in a northern European climate. Each strain
      could also be efficiently cultivated in a semi-continuous system for steady
      production of biomass and nutrient removal.

PMID- 24315942
TI  - Role of adenosine signalling and metabolism in beta-cell regeneration.
AB  - Glucose homeostasis, which is controlled by the endocrine cells of the pancreas,
      is disrupted in both type I and type II diabetes. Deficiency in the number of
      insulin-producing beta cells - a primary cause of type I diabetes and a secondary
      contributor of type II diabetes - leads to hyperglycemia and hence an increase in
      the need for insulin. Although diabetes can be controlled with insulin
      injections, a curative approach is needed. A potential approach to curing
      diabetes involves regenerating the beta-cell mass, e.g. by increasing beta-cell
      proliferation, survival, neogenesis or transdifferentiation. The nucleoside
      adenosine and its cognate nucleotide ATP have long been known to affect insulin
      secretion, but have more recently been shown to increase beta-cell proliferation
      during homeostatic control and regeneration of the beta-cell mass. Adenosine is
      also known to have anti-inflammatory properties, and agonism of adenosine
      receptors can promote the survival of beta-cells in an inflammatory
      microenvironment. In this review, both intracellular and extracellular mechanisms
      of adenosine and ATP are discussed in terms of their established and putative
      effects on beta-cell regeneration. 

PMID- 24315943
TI  - Characterization of an immunologically active pectin from the fruits of Lycium
      ruthenicum.
AB  - An immunologically active pectin, named LRGP5, was firstly isolated from the
      fruits of Lycium ruthenicum Murr. It contained rhamnose, arabinose, xylose,
      galactose and galacturonic acid in the molar ratio of 1.0:2.2:0.5:1.2:4.7. Its
      molecular weight was estimated to be approximately 1.37 * 10(5)Da by high
      performance gel permeation chromatography. The structure was elucidated using
      methylation analysis, partial acid hydrolysis, NMR and ESI-MS analysis. Results
      showed that LRGP5 consisted of a (1 -> 4)-linked galacturonic acid backbone
      occasionally interrupted by (1 -> 2)-linked rhamnose. The side chains were
      attached to position 4 of the rhamnosyl units, including (1 -> 3)-linked
      arabinose, (1 -> 3)-linked galactose, (1 -> 3,6)-linked galactose, (1 -> 4)
      linked galacturonic acid, (1 -> 2)-linked rhamnose and (1 -> 2,4)-linked
      rhamnose, and the termini were arabinose and rhamnose. Immunological assay
      results demonstrated that LRGP5 could significantly promote macrophage
      proliferation and enhance the secretion of nitrogen monoxide in vitro.

PMID- 24315944
TI  - Structural analysis and antioxidant activities of polysaccharide isolated from
      Jinqian mushroom.
AB  - Jinqian mushroom is a precious edible mushroom with delicious taste and high
      nutritional value. In this paper, a polysaccharide fraction JQPs was isolated and
      purified from the fruiting body of Jinqian mushroom. The chemical structure,
      chain conformation and antioxidant activities of JQPs were investigated. The
      results indicated that JQPs was mainly composed of glucose with trace amounts of
      xylose. The backbone of JQPs consisted of beta-(1 -> 3)-D-glucan with beta-(1 ->
      6)-glucosyl side chain. The chain conformation analysis showed that JQPs was a
      triple helical polysaccharide. The antioxidant activity tests in vitro revealed
      that JQPs exhibited high DPPH radical and ABTS radical scavenging activities,
      moderate superoxide radical and hydroxyl radical scavenging activities, low
      reducing power and Fe(2+) chelating activities. The results suggested that JQPs
      could be used as a potential natural antioxidant.

PMID- 24315945
TI  - Taguchi design for optimization and development of antibacterial drug-loaded PLGA
      nanoparticles.
AB  - This research report was to develop Cefixime loaded polylactide-co-glycolide
      (PLGA) nanoparticles using modified precipitation method. TEM analysis indicated
      formation of well-formed, smooth, spherical nanoparticles with no aggregates
      whereas XRD recommended dispersion of drug in PLGA carrier system in amorphous
      form. The polymer and stabilizer concentration and organic to aqueous ratio were
      found to be significant factors for nanoparticles and their optimization using
      Taguchi design (L9). The design formulations showed entrapment efficiency (EE),
      particle size and poly-dispersity index (PDI) ranging 68.31 +/- 1.74%, 159.8
      157.7 nm and 0.126-0.149, respectively indicated small and stable nanoparticles
      with good homogeneity and encapsulation. The design optimized formulation drug
      release and permeation studies demonstrated that it is four times sustained
      release behavior and 1.74 times better permeation than free drug. The result of
      microbiological assay also suggested that optimized formulation has significant
      antibacterial activity against intracellular multidrug resistance (MDR) of
      Salmonella typhi.

PMID- 24315946
TI  - Synthesis, characterization and in vitro anti-diabetic activity of catechin
      grafted inulin.
AB  - In this study, a novel biological macromolecule with strong in vitro anti
      diabetic activity was developed by grafting catechin onto inulin via a free
      radical mediated method. The characterization, alpha-glucosidase and alpha
      amylase inhibitory activities of catechin grafted inulin (catechin-g-inulin) were
      investigated. Results showed that the grafting ratio of catechin-g-inulin was
      124.8 mg CAE/g. UV-vis spectrum of catechin-g-inulin exhibited a new band at 280
      nm, attributing to B ring of catechin moiety. FT-IR spectrum of catechin-g-inulin
      showed new absorption bands between 1540 and 1418 cm(-1), attributing to CC
      stretching vibration of catechin moiety. (1)H NMR spectrum of catechin-g-inulin
      preserved all the characteristic proton signals of inulin and partial signals of
      catechin. These all confirmed the successful grafting copolymerization.
      Conjugation probably occurred between OH of inulin (C-6) and H-6/H-8 of catechin
      (A ring). Catechin-g-inulin also exhibited increased thermal stability and
      crystallinity as compared to inulin. Moreover, in vitro anti-diabetic assays
      showed the alpha-glucosidase inhibitory activity decreased in the order of
      catechin-g-inulin>catechin>acarbose>inulin, and alpha-amylase inhibitory activity
      decreased in the order of catechin-g-inulin>acarbose>catechin>inulin. These
      indicated the potential of catechin-g-inulin in the development of a novel
      effective anti-diabetic agent.

PMID- 24315947
TI  - Preparation and characterization of dry method esterified starch/polylactic acid
      composite materials.
AB  - Corn starch and maleic anhydride were synthesized from a maleic anhydride
      esterified starch by dry method. Fourier transform infrared spectroscopy (FTIR)
      was used for the qualitative analysis of the esterified starches. The reaction
      efficiency of dry method esterified starch reached 92.34%. The dry method
      esterified starch was blended with polylactic acid (PLA), and the mixture was
      melted and extruded to produce the esterified starch/polylactic acid (ES/PLA)
      composites. The degree of crystallinity of the ES/PLA was lower than that of the
      NS/PLA, indicating that the relative dependence between these two components of
      starch and polylactic acid was enhanced. Scanning electron microscopy (SEM)
      indicated that the dry method esterified starch increased the two-phase interface
      compatibility of the composites, thereby improving the tensile strength, bending
      strength, and elongation at break of the ES/PLA composite. The introduction of a
      hydrophobic ester bond and increase in interface compatibility led to an increase
      in ES/PLA water resistance. Melt index determination results showed that starch
      esterification modification had improved the melt flow properties of starch/PLA
      composite material. Strain scanning also showed that the compatibility of ES/PLA
      was increased. While frequency scanning showed that the storage modulus and
      complex viscosity of ES/PLA was less than that of NS/PLA. 

PMID- 24315948
TI  - Effects of Lactobacillus plantarum immobilization in alginate coated with
      chitosan and gelatin on antibacterial activity.
AB  - The present study aimed to investigate and evaluate the efficiency of
      immobilizing the Lactobacillus plantarum TN9 strain in alginate using chitosan
      and gelatin as coating materials, in terms of viability and antibacterial
      activity. The results indicate that maximum concentrations of L. plantarum TN9
      strain were produced with 2% sodium alginate, 10(8)UFC/ml, and 1M calcium
      chloride. The viability and antibacterial activity of the L. plantarum TN9
      cultures before and after immobilization in alginate, chitosan-coated alginate,
      and gelatin-coated alginate, were studied. The findings revealed that the
      viability of encapsulated L. plantarum could be preserved more than 5.8 log
      CFU/ml after 35 day of incubation at 4  degrees C, and no effects were observed
      when gelatin was used. The antibacterial activity of encapsulated L. plantarum
      TN9 against Gram-positive and Gram-negative pathogenic bacteria was enhanced in
      the presence of chitosan coating materials, and no activity was observed in the
      presence of gelatin. The effects of catalase and proteolytic enzymes on the
      culture supernatant of L. plantarum TN9 were also investigated, and the results
      suggested that the antibacterial activity observed was due to the production of
      organic acids. Taken together, the findings indicated that immobilization in
      chitosan enhanced the antibacterial activity of L. plantarum TN9 against several
      pathogenic bacteria. This encapsulated strain could be considered as a potential
      strong candidate for future application as an additive in the food and animal
      feed industries.

PMID- 24315949
TI  - Anti-hepatoma activity and mechanism of corn silk polysaccharides in H22 tumor
      bearing mice.
AB  - Corn silk is a well known traditional Chinese herbal medicine and corn silk
      polysaccharides (CSP) possess multiple pharmacological activities. However, the
      antitumor effect of CSP on hepatocarcinoma has not been studied. This study aimed
      to investigate the effects of CSP on tumor growth and immune functions in H22
      hepatocarcinoma tumor-bearing mice. The results demonstrated that CSP could not
      only inhibit the tumor growth, but also extended the survival time of H22 tumor
      bearing mice. Besides, CSP administration could increase the body weight,
      peripheral white blood cells (WBC) count, thymus index and spleen index of H22
      tumor-bearing mice. Furthermore, the production of serum cytokines in H22 tumor
      bearing mice, such as IL-2, IL-6 and TNF-alpha, was enhanced by CSP treatment. In
      addition, no toxicological effects were observed on hepatic function and renal
      function in CSP-treated mice transplanted H22 tumor cells. In summary, this
      experimental finding indicated that CSP could elevate the immune functions in H22
      tumor-bearing mice to enhance its antitumor activity and CSP seems to be a safe
      and effective agent for the treatment of hepatocellular carcinoma. 

PMID- 24315950
TI  - Biodistribution profiling of the chemical modified hyaluronic acid derivatives
      used for oral delivery system.
AB  - A series of adipic acid dihydrazide (ADH)-modified hyaluronic acid (HA-ADH)
      compounds were synthesized and conjugated with QDots (QDots-HA conjugates) to
      assess the effects of the molecular weight (MW) and extent of chemical
      modification of HA on its biodistribution. Their physicochemical structures were
      confirmed by complementary application of GPC, (1)H NMR, FTIR, and UV-vis
      spectroscopic methods. In vivo imaging of QDots-HA conjugates after oral
      administration was analyzed to investigate their biodistribution in nude mice.
      Simultaneously, real-time bioimaging was confirmed by an anatomical analysis to
      investigate the organ-specific accumulation of conjugates. QDot-HA conjugates
      with a higher MW of HA or high modification presented relatively slow clearance
      leading to an extension of the retention time for up to 10 days, whereas those
      with lower MWs of HA or a low modification extent exhibited quick absorption and
      elimination after oral administration. Taken together, HA derivatives with
      suitable MWs and chemical modification extents can be used to design new, more
      sophisticated, and intelligent HA-based vehicles for oral delivery with diverse
      characteristics. 

PMID- 24315951
TI  - Immunoglobulin A response to acute stress in intimate partner violence
      perpetrators: the role of anger expression-out and testosterone.
AB  - Aggressive behavior and immune activity are shown to be positively associated in
      perpetrators of intimate partner violence (IPV). This relationship follows an
      inverted-U curve, with the most violent individuals showing lower levels of
      immunocompetence than those with a history of moderate violence. Moreover, the
      activational and organizational effects of testosterone (T) may indirectly
      stimulate the immune response. Given this, we used the Trier Social Stress Test
      to establish whether the salivary immunoglobulin A (sIgA) response to acute
      stress was a specific psychobiological feature in perpetrators of intimate
      partner violence (IPV). IPV perpetrators showed higher sIgA levels than controls
      for the preparation period. Moreover, higher anger expression and T (baseline and
      AUCi) were only related to higher sIgA levels in IPV perpetrators. We hypothesize
      that in IPV perpetrators, the use of violence against partners could benefit
      their psychological well-being - through immunological modifications such as
      mucosal immunity changes expressed by the sIgA - and so be rewarding for them.
      This research may provide a wider explanation of why IPV perpetrators use
      violence against their partners. 

PMID- 24315952
TI  - A methodology to compensate for individual differences in psychophysiological
      assessment.
AB  - The main methodological drawback to use physiological measures as indicators of
      arousal is, the large interindividual variability of autonomic responses
      hindering the direct comparability, between individuals. The present methodology
      has been tested in two cohorts (n1=910, n2=845) of, pilot applicants during a
      selection procedure. Physiological data were obtained during two mentally,
      demanding tasks and during a Flight Simulator Test. Five typical Autonomic
      Response Patterns (ARP), were identified by cluster analyses. Autonomic spaces
      were constructed separately for each group of, subjects having the same typical
      ARP, on the basis of their normalized eigenvectors. The length of the, vector sum
      of scores on autonomic space dimensions provided an integral index for arousal,
      labeled, Psychophysiological Arousal Value (PAV). The PAV still reflected the
      changes in mental load during the, tests, but equalized physiological differences
      among ARP-groups. The results obtained in the first, cohort were verified in the
      second cohort. 

PMID- 24315953
TI  - Coherence explored between emotion components: evidence from event-related
      potentials and facial electromyography.
AB  - Componential theories assume that emotion episodes consist of emergent and
      dynamic response changes to relevant events in different components, such as
      appraisal, physiology, motivation, expression, and subjective feeling. In
      particular, Scherer's Component Process Model hypothesizes that subjective
      feeling emerges when the synchronization (or coherence) of appraisal-driven
      changes between emotion components has reached a critical threshold. We examined
      the prerequisite of this synchronization hypothesis for appraisal-driven response
      changes in facial expression. The appraisal process was manipulated by using
      feedback stimuli, presented in a gambling task. Participants' responses to the
      feedback were investigated in concurrently recorded brain activity related to
      appraisal (event-related potentials, ERP) and facial muscle activity
      (electromyography, EMG). Using principal component analysis, the prediction of
      appraisal-driven response changes in facial EMG was examined. Results support
      this prediction: early cognitive processes (related to the feedback-related
      negativity) seem to primarily affect the upper face, whereas processes that
      modulate P300 amplitudes tend to predominantly drive cheek region responses. 

PMID- 24315954
TI  - GPR120 agonism as a countermeasure against metabolic diseases.
AB  - Obesity, type 2 diabetes mellitus and cardiovascular disease are at epidemic
      proportions in developed nations globally, representing major causes of ill
      health and premature death. The search for drug targets to counter the growing
      prevalence of metabolic diseases has uncovered G-protein-coupled receptor 120
      (GPR120). GPR120 agonism has been shown to improve inflammation and metabolic
      health on a systemic level via regulation of adiposity, gastrointestinal peptide
      secretion, taste preference and glucose homeostasis. Therefore, GPR120 agonists
      present as a novel therapeutic option that could be exploited for the treatment
      of impaired metabolic health. This review summarizes the current knowledge of
      GPR120 functionality and the potential applications of GPR120-specific agonists
      for the treatment of disease states such as obesity, type 2 diabetes mellitus and
      cardiovascular disease. 

PMID- 24315955
TI  - Generalized ligamentous laxity may be a predisposing factor for musculoskeletal
      injuries.
AB  - OBJECTIVES: The aim of this study is to determine if generalized ligamentous
      laxity may be a predisposing factor for musculoskeletal injuries in young males.
      We hypothesized that generalized ligamentous laxity would be more common in
      individuals with musculoskeletal injuries compared with controls. DESIGN:
      Prospective Age- and Gender-matched Case-Control Study examined generalized
      ligamentous laxity in 100 consecutive individuals aged 18-25 who reported with
      musculoskeletal injuries to a primary healthcare center in the military. The
      Beighton score was used to measure joint laxity, which was determined to be
      present by overall scores equal to or exceeding 4. The control group comprised
      100 age- and gender-matched individuals without any musculoskeletal injuries or
      complaints. The prevalence of generalized ligamentous laxity was then compared
      between cases and controls. Subgroup analyses were also performed to evaluate the
      epidemiology of injury within the cases. METHODS: This prospective case-control
      study examined generalized ligamentous laxity in 100 consecutive individuals aged
      18-25 who reported with musculoskeletal injuries to a primary healthcare center
      in the military. The Beighton score was used to measure joint laxity, which was
      determined to be present by overall scores equal to or exceeding 4. The control
      group comprised 100 age- and gender-matched individuals without any
      musculoskeletal injuries or complaints. The prevalence of generalized ligamentous
      laxity was then compared between cases and controls. RESULTS: Generalized
      ligamentous laxity was present in 12% of the cases compared with 4% of controls
      Clearer to be presented as (P-value: 0.043). Individuals who presented with
      musculoskeletal injuries were 3.35 times more likely to have generalized
      ligamentous laxity as compared to controls. Lower limb injuries were more common
      than upper limb injuries amongst the cases. CONCLUSIONS: Generalized ligamentous
      laxity was more common in individuals who presented with a musculoskeletal
      injury. Hence, it may be a predisposing factor for musculoskeletal injuries.

PMID- 24315956
TI  - Exercise & Sports Science Australia (ESSA) position statement on exercise
      prescription for patients with peripheral arterial disease and intermittent
      claudication.
AB  - OBJECTIVES: Peripheral arterial disease (PAD) is characterised by atherosclerotic
      stenosis or occlusion of the arteries of the lower limbs, resulting in an
      impairment of blood flow to the legs. Patients with PAD have a significant
      reduction in their physical capacity and are limited during activities such as
      walking by intermittent claudication. DESIGN: Position stand. METHODS: Synthesis
      of published work within the field of exercise training and peripheral arterial
      disease. RESULTS: Supervised exercise training is considered the most effective
      treatment for increasing exercise tolerance in patients with PAD, and is also
      associated with improvements in daily physical activity and quality of life, and
      a reduction is cardiovascular disease risk. Exercise should be prescribed and
      progressed for patients individually, taking into consideration their disease
      severity, exercise tolerance and relevant comorbidities. CONCLUSIONS: While
      walking programs are beneficial and frequently prescribed, other forms of aerobic
      exercise such as cycling or arm-cranking may also be incorporated as tolerated by
      patients. Forty minutes of accumulated aerobic activity, three times per week, is
      recommended for most patients. Patients should be encouraged to commence exercise
      at a moderate intensity, and should stop and rest if claudication pain becomes
      severe. Resistance training should also be included on at least two days per week
      with the goal of improving muscular strength and endurance. Comorbidities such as
      musculoskeletal complaints, hypertension, diabetes and peripheral neuropathy are
      common in patients with PAD and may exacerbate their functional limitations.
      Given the high cardiovascular risk associated with PAD, it is important that
      patients are appropriately monitored during exercise.

PMID- 24315957
TI  - Role of diffusion-weighted imaging as an adjunct to contrast-enhanced breast MRI
      in evaluating residual breast cancer following neoadjuvant chemotherapy.
AB  - OBJECTIVE: To investigate whether the addition of diffusion-weighted imaging
      (DWI) to dynamic contrast-enhanced MRI (DCE-MRI) improves diagnostic performance
      in predicting pathologic response and residual breast cancer size following
      neoadjuvant chemotherapy. MATERIALS AND METHODS: A total of 78 consecutive
      patients who underwent preoperative breast MRI with DWI following neoadjuvant
      chemotherapy were enrolled. DWI was performed on a 1.5 T system with b values of
      0 and 750 s/mm. or on a 3T system with b values of 0 and 800 or 0 and 1,000 s/mm.
      The images on DCE-MRI alone, DWI alone, and DCE-MRI plus DWI were retrospectively
      reviewed. We evaluated the diagnostic performances of the three MRI protocols for
      the detection of residual cancer. The tumor size as predicted by MRI was compared
      with histopathologic findings. Apparent diffusion coefficient (ADC) values were
      also compared between the groups with and without residual cancer. RESULTS: Of
      the 78 patients, 59 (75.6%) had residual cancer. For detection of residual
      cancer, DCE-MRI plus DWI had higher specificity (80.0%), accuracy (91.0%), and
      PPV (93.2%) than DCE-MRI or DWI alone (P=0.004, P=0.007, and P=0.034,
      respectively). The ICC values for residual cancer size between MRI and
      histopathology were 0.891 for DCE-MRI plus DWI, 0.792 for DCE-MRI, and 0.773 for
      DWI. ADC values showed no significant differences between residual cancer and
      chemotherapeutic changes (P=0.130). CONCLUSIONS: The addition of DWI to DCE-MRI
      significantly improved diagnostic performance in predicting pathologic response
      and residual breast cancer size after neoadjuvant chemotherapy.

PMID- 24315958
TI  - P53-participated cellular and molecular responses to irradiation are cell
      differentiation-determined in murine intestinal epithelium.
AB  - AIM: Cells respond differently to DNA damaging agents, which may related to cell
      context and differentiation status. The aim of present study was to observe the
      cellular and molecular responses of cells in different differentiation status to
      ionizing irradiation (IR). METHODS: Crypt-villus unit of murine small intestine
      was adopted as a cell differentiation model. DNA damage responses (DDRs) of crypt
      and villus were observed 1-24 h after 12 Gy IR using gene expression microarray
      analysis, immunohistochemical staining, Western blotting and Electrophoretic
      Mobility Shift Assay. RESULTS: Microarray analysis revealed that most
      differentially expressed genes were related to p53 signaling pathway in crypt 4h
      after IR and in both crypt and villus 24h after IR. In crypt stem
      cells/progenitor cells, H2AX was phosphorylated and dephosphorylated quickly,
      Ki67 attenuated, cell apoptosis enhanced, phosphorylated P53 increased and
      translocated into nuclear with the ability to bind p53-specific sequence. In
      upper crypt (transit amplifying cells) and crypt-villus junction, cells kept
      survive and proliferate as indicated by retained Ki67 expression, suppressed p53
      activation, and rare apoptosis. CONCLUSIONS: DDRs varied with cell
      differentiation status and cell function in small intestinal epithelium. P53
      signaling pathway could be an important regulatory mechanism of DDRs.

PMID- 24315959
TI  - The critical role of Sestrin 1 in regulating the proliferation of cardiac
      fibroblasts.
AB  - The proliferation of cardiac fibroblasts is pivotal in the development of cardiac
      fibrosis. Sestrin 1, which functions as antioxidant, plays diverse roles in the
      regulation of proliferation and cellular injury that is induced by oxidative
      stress. However, little is known regarding the impact of Sestrin 1 on the
      proliferation of cardiac fibroblasts. In the present study, with knockdown of
      Sestrin 1 by siRNA, we surveyed the effect of Sestrin 1 on cardiac fibroblast
      proliferation. Downregulation of Sestrin 1 promotes Ang II-induced proliferation
      of cardiac fibroblasts, leading to increased DNA synthesis and collagen
      production. Moreover, in the absence of Ang II, a similar phenotype to the basal
      condition was detected with silencing of Sestrin 1. Further analysis of the pro
      proliferating signals revealed that knockdown of Sestrin 1 significantly
      activated ERK1/2 and mTOR, meanwhile, downregulation of Sestrin 1 also enhanced
      the expression of collagen type I and CTGF, which play important role in the
      cardiac fibrosis. Consistent with the antioxidant property of Sestrin 1, we
      determined that the proliferation induced by silence of Sestrin 1 was accompanied
      by a remarkably enhanced production of reactive oxygen species (ROS). However,
      diminishing ROS by NAC, a potent antioxidant, could only partly repress the pro
      proliferative effect of Sestrin 1-downregulation. Consequently, our study
      demonstrated that Sestrin 1 plays an important role in the proliferation of
      cardiac fibroblasts, and the effect could be partly mediated by decreased
      oxidative stress. 

PMID- 24315960
TI  - Actin-mediated transovarial transmission of a yeastlike symbiont in the brown
      planthopper.
AB  - The brown planthopper Nilaparvata lugens (Hemiptera, Delphacidae) harbors an
      obligate endosymbiont called the yeastlike symbiont (YLS) in their abdominal fat
      body. YLS, a filamentous ascomycete belonging to the family Clavicipitaceae, does
      not spend any part of its life cycle outside the planthopper's body. The YLS is
      transferred to the next generation via transovarial transmission; it enters the
      epithelial plug at the posterior end of the host female's ovariole and is
      transferred to her offspring. In the present study, microscopic examination
      revealed that actin filaments play an important role in the transmission of YLS.
      An irregular cell protrusion on the surface of the epithelial plug facilitated
      the uptake of the YLS, which was then incorporated into the epithelial plug cell.
      Actin assembly apparently produces the protrusion and actin appears to
      participate in almost every stage of the process, from the entry of the YLS into
      the epithelial plug to its delivery to the oocyte. The epithelial plug employs a
      recognition system for YLS, which drastically changes the cell surface structure
      to enable the YLS to enter the ovariole. 

PMID- 24315962
TI  - Effects of iron therapy on blood lead concentrations in infants.
AB  - To determine whether blood lead concentration is elevated in iron-deficient
      infants, blood lead and serum ferritin concentrations, serum iron/transferring
      iron-binding capacity (Fe/TIBC) and complete blood counts were measured in 30
      iron deficient and 35 control infants, aged 6-24 months. All 30 iron-deficient
      infants received iron supplementation (ferric hydroxide-polymaltose complex,
      6mg/kg Fe(3+)/day) for 1-6 months. Blood lead concentrations were measured in 18
      of the iron deficient infants after their ferritin levels returned to the normal
      range. The geometric mean blood lead concentration was higher in iron deficient
      than in control infants (1.846 vs. 1.416MUg/dL). After iron therapy, the blood
      lead levels of iron-deficient infants decreased significantly compared with pre
      treatment levels (1.785 vs. 2.386MUg/dL), and the hemoglobin and ferritin
      concentrations increased significantly. These findings indicate that iron
      deficiency increases blood lead concentrations in infants with very low blood
      lead concentrations. 

PMID- 24315961
TI  - Mechanisms of nitrite bioactivation.
AB  - It is now accepted that the anion nitrite, once considered an inert oxidation
      product of nitric oxide (NO), contributes to hypoxic vasodilation, physiological
      blood pressure control, and redox signaling. As such, its application in
      therapeutics is being actively tested in pre-clinical models and in human phase I
      II clinical trials. Major pathways for nitrite bioactivation involve its
      reduction to NO by members of the hemoglobin or molybdopterin family of proteins,
      or catalyzed dysproportionation. These conversions occur preferentially under
      hypoxic and acidic conditions. A number of enzymatic systems reduce nitrite to NO
      and their activity and importance are defined by oxygen tension, specific organ
      system and allosteric and redox effectors. In this work, we review different
      proposed mechanisms of nitrite bioactivation, focusing on analysis of kinetics
      and experimental evidence for the relevance of each mechanism under different
      conditions. 

PMID- 24315963
TI  - Trace elements, oxidative stress and glycemic control in young people with type 1
      diabetes mellitus.
AB  - Trace elements and oxidative stress are associated with glycemic control and
      diabetic complications in type 1 diabetes mellitus. In this study, we analyzed
      the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and
      malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in
      33 type 1 diabetic patients with optimal and suboptimal glycemic control
      (HbA1C<9.0%) and 40 patients with poor glycemic control (HbA1C>=9%) and 27 age-
      and sex-matched non-diabetic controls to evaluate the differences between these
      markers in different glycemic control states. Diabetic patients, especially poor
      glycemic-control subjects (HbA1C>=9%), exhibited significantly lower levels of
      serum zinc and increased levels of serum copper (and, therefore, increased serum
      copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG,
      relative to non-diabetic subjects. Furthermore, significant correlations existed
      in these patients between the serum copper, serum copper-to-zinc ratio, and
      urinary MDA (all p<0.001) and the levels of urinary 8-OHdG (p=0.007) and HbA1C.
      Our results suggest that high serum copper levels and oxidative stress correlate
      with glycemic control. Therefore, strict glycemic control, decreased oxidative
      stress, and a lower copper concentration might prevent diabetic complications in
      patients with type 1 diabetes mellitus. 

PMID- 24315964
TI  - Electrocardiography-inclusive screening strategies for detection of
      cardiovascular abnormalities in high school athletes.
AB  - BACKGROUND: The best protocol for cardiovascular preparticipation screening (PPS)
      in young athletes is uncertain. OBJECTIVE: The purpose of this study was to
      determine the value of integrating electrocardiographic (ECG) testing with
      standard history and physical examination during PPS to identify potentially
      serious cardiovascular abnormalities in young athletes. METHODS: A total of 2017
      high school athletes seeking clearance for competitive sports were prospectively
      evaluated using a standardized history and physical examination, 12-lead ECG, and
      two-dimensional echocardiogram (echo). Primary outcome measures included the
      identification of cardiac disorders associated with sudden cardiac death.
      Secondary outcome measures included identification of abnormal, but nonlethal,
      cardiac conditions that required medical follow-up. RESULTS: Of these athletes,
      14.7% had an abnormal history or physical examination and 3.1% had an abnormal
      ECG based on modern ECG interpretation criteria. Five primary outcomes (1
      hypertrophic cardiomyopathy, 4 Wolff-Parkinson-White syndrome) and four secondary
      outcomes were identified. History and physical examination detected 40% of
      primary and 50% of secondary abnormalities. ECG detected all five primary
      abnormalities but none of the secondary abnormalities. Echo was abnormal in 1.2%
      and detected one primary and four secondary abnormalities. The false-positive
      rates for primary and secondary outcomes for history and physical examination and
      ECG were 14.5% and 2.8%, respectively. CONCLUSION: ECG adds value to PPS through
      increased detection of arrhythmogenic and structural cardiovascular conditions
      associated with sudden cardiac death. Use of modern ECG interpretation standards
      allows a low false-positive rate. Routine echo may detect other clinically
      important cardiac abnormalities, but its role in PPS remains uncertain.

PMID- 24315965
TI  - Eastern promises: Additive role of metabolic syndrome for thromboembolic risk
      stratification in Taiwanese atrial fibrillation patients.

PMID- 24315966
TI  - Clinical characteristics and outcomes of elderly patients treated with an
      implantable cardioverter-defibrillator or cardiac resynchronization therapy in a
      real-world setting: data from the Israeli ICD Registry.
AB  - BACKGROUND: Elderly patients are underrepresented in clinical trials of device
      therapy. OBJECTIVE: To provide real-world data regarding outcomes associated with
      device-based therapy in a large cohort of elderly patients enrolled in the
      Israeli ICD Registry. METHODS: Between July 2010 and June 2012, a total of 2807
      consecutive patients undergoing implanted cardioverter-defibrillator/cardiac
      resynchronization therapy-defibrillator (ICD/CRT-D) implantation were
      prospectively enrolled in the Israeli ICD Registry. For the present analysis,
      patients were categorized into 3 age groups: <=60 years (n = 1378 [49%]), 61-75
      years (n = 863 [31%]), and >75 years (n = 566 [20%]). RESULTS: Elderly patients
      (>75 years of age) had more comorbid conditions and were more likely to undergo
      CRT-D implantation (all P < .01). However, the rate of device-related
      complications associated with surgical reinterventions at 1 year was <3%
      regardless of age (P = .70 for the comparison among the 3 age groups).
      Multivariate analysis showed that the risk of heart failure or death and of
      appropriate ICD therapy for ventricular arrhythmias was significantly increased
      with increasing age among patients who received an ICD. In contrast, the age
      related increase in the risk of all end points was attenuated among patients who
      received CRT-D devices (all P values for age-by-device-type interactions are
      <.05). CONCLUSIONS: In a real-world scenario, elderly patients (>75 years of age)
      comprise approximately 20% of the ICD/CRT-D recipients and experience a device
      reintervention rate similar to that of their younger counterparts. Our data
      suggest that the association between advanced age and adverse clinical outcomes
      is attenuated in elderly patients implanted with CRT-D devices.

PMID- 24315967
TI  - Outcomes of patients requiring emergent surgical or endovascular intervention for
      catastrophic complications during transvenous lead extraction.
AB  - BACKGROUND: The outcomes of patients requiring emergent surgical or endovascular
      intervention during transvenous lead extraction (TLE) have not been well
      characterized. OBJECTIVES: To evaluate the incidence of catastrophic
      complications requiring emergent surgical or endovascular intervention during
      TLE, to describe the injuries, and to review patient management and outcomes.
      METHODS: Consecutive patients undergoing TLE of pacemaker and implantable
      cardioverter-defibrillator (ICD) leads at the Cleveland Clinic between August
      1996 and September 2012 were included in the analysis. RESULTS: A total of 5973
      (4436 [74.3%] pacemaker and 1537 [25.7%] ICD) leads were extracted during 3258
      TLE procedures (median [25th, 75th percentile] patient age 67.0 [55.0, 76.1]
      years; 69.2% men). The median (25th, 75th percentile) lead implant duration was
      4.9 (2.4, 8.4) years, and 2.0 (1.0, 2.0) leads were extracted per procedure.
      Powered sheaths were used in 2369 (72.7%) procedures. Twenty-five (0.8%) patients
      experienced catastrophic complications requiring emergent surgical or
      endovascular intervention. Twenty patients (0.6%) required either sternotomy (n =
      18) or thoracotomy (n = 2) for superior vena cava laceration (n = 15) and right
      atrial (n = 2) or ventricular (n = 3) perforation. Two patients required vascular
      repair at the procedural access site for either subclavian vein or artery
      laceration. Three patients were managed with an endovascular approach for
      superior vena cava laceration, left axillary artery laceration, and
      brachiocephalic vein and artery fistula. In-hospital mortality was 36.0% (6
      procedural/operative deaths and 3 deaths during the same hospitalization).
      CONCLUSIONS: Major vascular injury or cardiac perforation requiring emergent
      surgical or endovascular intervention during TLE is uncommon but carries
      significant in-hospital mortality. Despite high mortality, nearly two-thirds of
      these patients were rescued with immediate response and surgical or endovascular
      intervention.

PMID- 24315968
TI  - PCR assays for the identification of rare recombination types from VP1 to 3D
      genomic region of vaccine derived poliovirus strains.
AB  - Poliomyelitis has been effectively controlled by the use of inactivated
      poliovirus vaccine (IPV) or trivalent live attenuated oral poliovirus vaccine
      (OPV). Since 1964, the use of OPV in mass vaccinations has resulted in drastic
      reductions of the number of poliomyelitis cases caused by wild-type polioviruses.
      However, the characterization of OPV derivatives with increased neurovirulence,
      constituted a real problem with respect to OPV safety. Mutations at attenuating
      sites of the genome and recombination events between Sabin strains of the
      trivalent OPV vaccine have been correlated with the loss of the attenuated
      phenotype of OPV strains and the acquisition of traits characteristic of wild
      polioviruses. In consequence, early detection and characterization of recombinant
      evolved derivatives of vaccine strains is highly important. In this report, ten
      PCR assays are described which allow for the identification of rare recombination
      events located in VP1, 2A, 2C, 3A, 3C and 3D genomic regions and predominant
      recombination events located in 2C and 3D genomic regions of OPV derivatives.
      These assays could be readily implemented in diagnostics laboratories lacking
      sequencing facilities as a first approach for the early detection and
      characterization of recombinant OPV derivatives.

PMID- 24315969
TI  - Topical interferon-gamma neutralization prevents conjunctival goblet cell loss in
      experimental murine dry eye.
AB  - Evidence suggests that the cytokine interferon (IFN)-gamma released by natural
      killer and CD4(+) T cells contributes to the conjunctival goblet cell (GC) loss
      in dry eye. The purpose of this study was to investigate if topical
      neutralization of IFN-gamma prevents or alleviates GC loss in an experimental
      desiccating stress (DS) model of dry eye. In this study, we found that topical
      IFN-gamma neutralization significantly decreased DS-induced conjunctival GC loss.
      This was accompanied by decreased epithelial apoptosis, and increased IL-13 and
      decreased FoxA2 expression in the forniceal conjunctiva. To establish that IFN
      gamma produced by pathogenic CD4(+) T cells contributes to DS-induced GC loss,
      adoptive transfer of CD4(+) T cells isolated from DS exposed donors to naive RAG
      1(-/-) recipient mice was performed. Similar to the donor mice, topical IFN-gamma
      neutralization decreased conjunctival GC loss, suppressed apoptosis and increased
      IL-13 expression in adoptive transfer recipients. In summary, this study
      demonstrated that topical neutralization of IFN-gamma prevents GC loss via
      modulating apoptosis and maintaining IL-13 signaling. 

PMID- 24315970
TI  - PEGylation of G-CSF in organic solvent markedly increase the efficacy and
      reactivity through protein unfolding, hydrolysis inhibition and solvent effect.
AB  - Previous studies demonstrated that hydrophobic proteins could be PEGylated in
      organic phase rather than water phase. It is still not known what the difference
      is for a hydrophilic protein's PEGylation in these two different phases. In this
      study, granulocyte colony stimulating factor (G-CSF) was dissolved in neat
      dimethyl sulfoxide (DMSO) and was PEGylated. In comparison with the PEGylation in
      water solution, the PEGylation degree in the organic solvent increased by 33% and
      42% for PEG-maleimide (MAL-PEG) and PEG-succinimidyl carbonate (SC-PEG)
      respectively. Structure analysis revealed that the protein was unfolded in DMSO,
      which could make the PEGylated sites of G-CSF easily accessible. The hydrolysis
      half-life in water solution was 40min and 9h for SC-PEG and MAL-PEG respectively.
      However, in DMSO solvent, PEGs were very stable and no hydrolysis could be
      detected. Stopped-flow demonstrated that the conjugation speed of G-CSF by MAL
      PEG and SC-PEG in DMSO were 1.6*10(4) and 2*10(2) times faster than those in
      aqueous solution. The remarkable acceleration could mainly be attributed to an
      increase of protein nucleophilicity in DMSO. The results of this study could be
      referential to industrial application where the cost of PEG reagents and the
      speed of reaction on large scale are very important. 

PMID- 24315971
TI  - Multi-site saturation by OmniChange yields a pH- and thermally improved phytase.
AB  - Directed evolution of Yersinia mollaretii phytase (Ymphytase) yielded an improved
      variant SM2P3E4 (also named M1; D52N, T77K, K139E, G187S, V298M) in our previous
      study. Variant M1 retained high specific activity (993U/mg; equivalent to 93% of
      wild-type activity) and improved thermal resistance (T50 improved by 1.5 degrees
      C compared to wild-type at 58 degrees C; 20min incubation time), making variant
      M1 an attractive enzyme for industrial applications. Recently, the OmniChange
      method was developed for multi-site saturation mutagenesis. The five sites
      identified in variant M1 were subjected to OmniChange saturation in order to
      explore whether a variant with higher activity, higher thermal resistance, and
      higher resistance at low pH (2-3h incubation was performed to mimic the gastric
      residence time of phytase) could be identified. Screening of a small library of
      1100 clones, covering <0.004% of the theoretical sequence space of 3.35*10(7)
      variants, yielded a Ymphytase variant with 32% improved residual activity (58
      degrees C for 20min), 2 degrees C increased apparent melting temperature (Tm),
      and 2-fold higher pH stability (pH 2.8; 3h incubation time) when compared to the
      wild-type Ymphytase. Compared to the M1 variant, the pH stability (pH 2.8; 3h
      incubation time) was improved by 3-fold, and thermal resistance as well as
      activity was improved slightly (residual activity: 32% compared to 20%; apparent
      Tm: 2 degrees C compared to 1.5 degrees C; activity difference <4%). 

PMID- 24315973
TI  - Distribution of late gadolinium enhancement in end-stage hypertrophic
      cardiomyopathy and dilated cardiomyopathy: differential diagnosis and prediction
      of cardiac outcome.
AB  - BACKGROUND: The prognostic implications of late gadolinium enhancement (LGE) have
      been evaluated in ischemic and non-ischemic cardiomyopathies. The present study
      analyzed LGE distribution in patients with end-stage hypertrophic cardiomyopathy
      (ES-HCM) and with dilated cardiomyopathy (DCM), and tried to identify high risk
      patients in DCM. METHODS: Eleven patients with ES-HCM and 72 with DCM underwent
      cine- and LGE-cardiac magnetic resonance and ultrasound cardiography. The patient
      outcome was analyzed retrospectively for 5years of follow-up. RESULTS: LGE
      distributed mainly in the inter-ventricular septum, but spread more diffusely
      into other left ventricular segments in patients with ES-HCM and in a certain
      part of patients with DCM. Thus, patients with DCM can be divided into three
      groups according to LGE distribution; no LGE (n=24), localized LGE (localized at
      septum, n=36), and extensive LGE (spread into other segments, n=12). Reverse
      remodeling occurred after treatment in patients with no LGE and with localized
      LGE, but did not in patients with extensive LGE and with ES-HCM. The event-free
      survival rate for composite outcome (cardiac death, hospitalization for
      decompensated heart failure or ventricular arrhythmias) was lowest in patients
      with extensive LGE (92%, 74% and 42% in no LGE, localized LGE, and extensive LGE,
      p=0.02 vs. no LGE), and was comparable to that in patients with ES-HCM (42%).
      CONCLUSIONS: In DCM, patients with extensive LGE showed no functional recovery
      and the lowest event-free survival rate that were comparable to patients with ES
      HCM. The analysis of LGE distribution may be valuable to predict reverse
      remodeling and to identify high-risk patients.

PMID- 24315974
TI  - Incentive relativity in middle aged rats.
AB  - Response to a reinforcer is affected by prior experience with different reward
      values of that reward, a phenomenon known as incentive relativity. Two different
      procedures to study this phenomenon are the incentive downshift (ID) and the
      consummatory anticipatory negative contrast (cANC), the former is an emotional
      cognitive protocol and the latter cognitive one. Aged rodents, as also well
      described in aged humans, exhibit alterations in cognitive functions. The main
      goal of this work was to evaluate the effect of age in the incentive' assessment
      using these two procedures. The results indicated that aged rats had an adequate
      assessment of the rewards but their performance is not completely comparable to
      that of young subjects. They recover faster from the ID and they had a cognitive
      impairment in the cANC. The results are discussed in relation to age-related
      changes in memory and emotion. 

PMID- 24315975
TI  - Postnatal developmental changes in the medial nucleus of the trapezoid body in a
      mouse model of auditory pathology.
AB  - Age-related hearing loss (AHL) is a multifactorial disorder characterized by a
      decline in peripheral and central auditory function. Here, we examined synaptic
      transmission in DBA/2 mice, which carry the AHL8 gene, at the identifiable
      glutamatergic synapse in the medial nucleus of the trapezoid body (MNTB), a
      nucleus in the superior olivary complex critical for acoustic timing. Mice
      exhibited raised auditory brainstem thresholds by P14, soon after hearing onset.
      Excitatory postsynaptic currents were prolonged; however, postsynaptic
      excitability was normal. By P18, high-frequency hearing loss was evident.
      Coincident with the onset of hearing loss, MNTB principal neurons displayed
      changes in intrinsic firing properties. These results suggest that changes in
      transmission in the superior olivary complex are associated with early onset
      hearing loss. 

PMID- 24315977
TI  - Production of medical radionuclides in Russia: status and future--a review.
AB  - We present a review of reactor and accelerator centers in Russia that produce
      medical isotopes, the majority of which are exported. In the near future, we
      anticipate increased isotope production for use in nuclear medicine in Russia.
      The existing linear accelerator at the Institute for Nuclear Research (Moscow
      Troitsk) and several prospective installations are considered to be particularly
      capable of providing mass production of radionuclides that can substitute, to a
      certain extent, for the traditional medical isotopes. 

PMID- 24315976
TI  - AMPA and GABA(A/B) receptor subunit expression in the cuneate nucleus of adult
      squirrel monkeys during peripheral nerve regeneration.
AB  - The primate somatosensory neuroaxis provides an excellent model system with which
      to investigate adult neural plasticity. Here, we report immunohistochemical
      staining data for AMPA and GABAA/B receptor subunits in the cuneate nucleus of
      adult squirrel monkeys 1 and 5 months after median nerve compression. This method
      of nerve injury allowed the investigation of the way in which patterns of
      receptor correlates change during peripheral nerve regeneration. These results
      are compared to cortical data collected within the same animals. As observed in
      the cortex, the pattern of subunit staining in the brainstem 1 month after nerve
      compression suggests that the sensory deprived nucleus enters a state of
      reorganization. That is, the expression of GluR2/3 AMPA receptor subunits is
      significantly increased, while GABA alpha1 and GABABR1b receptor subunits are
      significantly decreased. Five months after nerve injury, the pattern of subunit
      expression is again very similar to that observed in the infragranular layers of
      cortex. At this later time we observe a significant increase in GluR2/3 and
      GABABR1a, with no change in GABAAalpha1, and a significant decrease in GABABR1b.
      Together these results suggest that during reorganization and recovery from
      injury the brainstem and cortex are governed by homogeneous mechanisms of
      plasticity. 

PMID- 24315978
TI  - Role of PPAR, LXR, and PXR in epidermal homeostasis and inflammation.
AB  - Epidermal lipid synthesis and metabolism are regulated by nuclear hormone
      receptors (NHR) and in turn epidermal lipid metabolites can serve as ligands to
      NHR. NHR form a large superfamily of receptors modulating gene transcription
      through DNA binding. A subgroup of these receptors is ligand-activated and
      heterodimerizes with the retinoid X receptor including peroxisome proliferator
      activated receptor (PPAR), liver X receptor (LXR) and pregnane X receptor (PXR).
      Several isotypes of these receptors exist, all of which are expressed in skin. In
      keratinocytes, ligand activation of PPARs and LXRs stimulates differentiation,
      induces lipid accumulation, and accelerates epidermal barrier regeneration. In
      the cutaneous immune system, ligand activation of all three receptors, PPAR, LXR,
      and PXR, has inhibitory properties, partially mediated by downregulation of the
      NF-kappaB pathway. PXR also has antifibrotic effects in the skin correlating with
      TGF-beta inhibition. In summary, ligands of PPAR, LXR and PXR exert beneficial
      therapeutic effects in skin disease and represent promising targets for future
      therapeutic approaches in dermatology. This article is part of a Special Issue
      entitled The Important Role of Lipids in the Epidermis and their Role in the
      Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R.
      Feingold and Peter Elias. 

PMID- 24315980
TI  - Effects of exercise training programs on physical performance and quality of life
      in patients with metastatic lung cancer undergoing palliative chemotherapy--a
      study protocol.
AB  - PURPOSE: The aims of the study protocol are to investigate different adapted
      physical training programs in patients with advanced lung cancer undergoing
      palliative chemo- or radiotherapy and to evaluate their effects on physical
      performance, quality of life, symptom burden, and efficacy of oncologic
      treatment. METHODS: Patients will be randomized into three study arms:
      interventional group 1 performing aerobic exercise, interventional group 2
      performing resistance training, and a control group without specific physical
      training. Interventional training will be performed for 12 weeks consisting of
      two supervised and one self-instructed training sessions per week each.
      Respiratory therapy over 12 weeks is provided in all three study arms as an
      established supportive therapy in lung cancer patients. Primary efficacy endpoint
      is physical performance measured by peak oxygen consumption (VO(2)peak).
      Secondary efficacy endpoints include additional parameters of physical
      performance (resistance, lung function, perceived exertion, level of physical
      activity and IPAQ-questionnaire), health-related quality of life (EORTC QLQ C30
      questionnaire), disease and treatment related symptoms (Memorial Symptom
      Assessment Scale), biologic parameter (e.g. body composition, blood values of
      immune system, chronic inflammation, glucose and lipid metabolisms), and
      parameter of efficacy of oncologic treatment. DISCUSSION: The results of this
      study will offer an overview over possible effects of specific training
      interventions on health related quality of life, physical and psychological
      symptoms, and on the efficacy of oncologic treatment. The primary aim of this
      study is to detect adapted intervention programs for metastatic lung cancer
      undergoing palliative chemotherapy.

PMID- 24315979
TI  - Donepezil treatment of older adults with cognitive impairment and depression
      (DOTCODE study): clinical rationale and design.
AB  - Treatment strategies for patients with depression and cognitive impairment (DEP
      CI), who are at high risk to develop a clinical diagnosis of dementia, are not
      established. This issue is addressed in the donepezil treatment of cognitive
      impairment and depression (DOTCODE) pilot clinical trial. The DOTCODE study is
      the first long-term treatment trial that assesses differences in conversion to
      dementia and cognitive change in DEP-CI patients using a study design of open
      antidepressant medication plus add-on randomized, double-blind, placebo
      controlled treatment with the acetylcholinesterase inhibitor donepezil. In Phase
      1, DEP-CI patients receive optimized antidepressant treatment for 16 weeks. In
      Phase 2, antidepressant treatment is continued with the addition of randomized,
      double-blind treatment with donepezil or placebo. The total study duration for
      each patient is 78 weeks (18 months). Eighty DEP-CI outpatients (age 55 to 95
      years) are recruited: 40 at New York State Psychiatric Institute/Columbia
      University and 40 at Duke University Medical Center. The primary outcome is
      conversion to a clinical diagnosis of dementia. The secondary outcomes are
      cognitive change scores in Selective Reminding Test (SRT) total recall and the
      modified Alzheimer's Disease Assessment Scale (ADAS-cog). Other key assessments
      include the 24-item Hamilton Depression Rating Scale and antidepressant response;
      Clinical Global Impression (CGI) for depression, cognition, and global status;
      neuropsychological test battery for diagnosis; informant report of functional
      abilities (Pfeffer FAQ); and Treatment Emergent Symptom Scale (TESS) for somatic
      side effects. Apolipoprotein E epsilon4 status, odor identification deficits, and
      MRI entorhinal/hippocampal cortex atrophy at baseline are evaluated as
      neurobiological moderators of donepezil treatment effects.

PMID- 24315981
TI  - Chondroprotective activity of a detoxicated traditional Chinese medicine (Fuzi)
      of Aconitum carmichaeli Debx against severe-stage osteoarthritis model induced by
      mono-iodoacetate.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi is an effective but toxic traditional
      Chinese medicine (TCM) derived from Aconitum carmichaeli. In our previous study,
      detoxicated Fuzi (d-Fuzi) has been originally developed with no toxicity but
      significant efficacy. However, whether d-Fuzi can be used for therapy of
      osteoarthritis (OA), remain unknown. MATERIALS AND METHODS: Severe OA model was
      established by intra-articular mono-iodoacetate (MIA) injection (1.25mg) into
      rats and orally treated with 2g/ml d-Fuzi at a dosage of 7 ml/kg body weight for
      28 days. In vivo, the articular radiographic and histopathologic analyses were
      performed to qualitatively assess the chondroprotective effect of d-Fuzi,
      followed by quantitative measurements of bone density and Mankin scores. In
      vitro, such effect on chondrocyte viability after MIA attack was evaluated.
      Hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS) was performed for
      chemical analysis of d-Fuzi. RESULTS: d-Fuzi was demonstrated to possess
      chondroprotective activity on MIA-induced OA model by in vivo preventing the
      articular degeneration and the reducing of bone density and Mankin score, as well
      as by in vitro promoting the chondrocyte proliferation and inhibiting the MIA
      induced chondrocyte damage. A total of 23 compounds were identified in d-Fuzi,
      most of which were deduced as the non-toxic derivatives of aconite alkaloids.
      CONCLUSIONS: This is the first report regarding chondroprotective effect and
      chemical profile of d-Fuzi, originally revealing its great anti-OA potential and
      thereby providing a promising TCM candidate for OA therapy.

PMID- 24315982
TI  - A UPLC-MS/MS method for in vivo and in vitro pharmacokinetic studies of
      psoralenoside, isopsoralenoside, psoralen and isopsoralen from Psoralea
      corylifolia extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The dried fruit of Psoralea corylifolia L. has
      been used to prevent and treat vitiligo, osteoporosis, arthralgia and asthma in
      Traditional Chinese Medicine for some 1600 years. Psoralen (P), isopsoralen (IP),
      psoralenoside (PO) and isopsoralenoside (IPO) are the major coumarins and
      coumarin-related benzofuran glycosides in Psoraleae Fructus, which have been
      reported to show estrogen-like activity, osteoblastic proliferation accelerating
      activity, antitumor effects and antibacterial activity. The first aim of this
      study is to develop a rapid, sensitive and selective ultra performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS) approach for simultaneous
      determination of PO, IPO, P and IP in rat plasma and samples collected from in
      vitro incubation experiments. The second aim is to investigate the
      pharmacokinetic properties of PO, IPO, P and IP after oral administration of
      Psoralea corylifolia extract (PCE) to rats. The third aim is to confirm the
      biotransformation of PO to P or IPO to IP under gastrointestinal conditions.
      MATERIALS AND METHODS: A UPLC-MS/MS method with a C18 column and a mobile phase
      of methanol-0.1% aqueous formic acid was validated according to the criteria in
      FDA guidelines about bioanalytical method, which was developed to investigate the
      pharmacokinetic behavior of PO, IPO, P and IP from PCE and the metabolic pathways
      of PO to P or IPO to IP. RESULTS: The criteria for establishment of a new UPLC
      MS/MS method including selectivity, linearity, accuracy, precision, extraction
      recovery, matrix effect and stability were validated. This method was
      successfully applied to the quantitative determination of PO, IPO, P and IP in
      biological samples collected from both in vitro incubations and in vivo rat
      experiments. After oral administration of PCE to rat, pharmacokinetic parameters
      of these four compounds indicated that in vivo biotransformation may occur
      between PO and P or IPO and IP. Purified benzofuran glycosides fraction (PBGF),
      containing only PO and IPO, was orally administered to rats to further confirm
      the biotransformation of PO to P or IPO to IP under gastrointestinal conditions.
      An in vitro incubation study elucidated that PO and IPO were metabolized to P and
      IP by intestinal microflora through de-glucosylation. CONCLUSIONS: This paper
      developed a rapid, sensitive and selective UPLC-MS/MS method for simultaneous
      determination of PO, IPO, P and IP from PCE in biological samples, and
      investigated on their comprehensive in vivo and in vitro pharmacokinetic studies.
      These obtained results showed that the metabolism by intestinal bacteria plays an
      important role in pharmacological effects of orally administered PCE.

PMID- 24315983
TI  - From local to global-fifty years of research on Salvia divinorum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In 1962 ethnopharmacologists, Hofmann and Wasson,
      undertook an expedition to Oaxaca, Mexico. These two researchers were the first
      scientists to collect a flowering specimen of Salvia divinorum allowing the
      identification of this species. While the species' traditional use is confined to
      a very small region of Mexico, since Hofmann and Wasson's expedition 50 years
      ago, Salvia divinorum has become globally recognized for its main active
      constituent, the diterpene salvinorin A, which has a unique effect on human
      physiology. Salvinorin A is a kappa-opioid agonist and the first reported
      psychoactive diterpene. METHODS: This review concentrates on the investigation of
      Salvia divinorum over the last 50 years including ethnobotany, ethnopharmacology,
      taxonomy, systematics, genetics, chemistry and pharmacodynamic and
      pharmacokinetic research. For the purpose of this review, online search engines
      were used to find relevant research. Searches were conducted between October 2011
      and September 2013 using the search term "Salvia divinorum". Papers were excluded
      if they described synthetic chemical synthesis of salvinorin A or analogues.
      RESULTS: Ethnobotanically there is a comprehensive body of research describing
      the traditional Mazatec use of the plant, however, the modern ethnobotanical use
      of this plant is not well documented. There are a limited number of botanical
      investigations into this plant and there are still several aspects of the botany
      of Salvia divinorum which need further investigation. One study has investigated
      the phylogenetic relationship of Salvia divinorum to other species in the genus.
      To date the main focus of chemistry research on Salvia divinorum has been
      salvinorin A, the main active compound in Salvia divinorum, and other related
      diterpenoids. Finally, the effects of salvinorin A, a KOR agonist, have primarily
      been investigated using animal models. CONCLUSIONS: As Salvia divinorum use
      increases worldwide, the emerging cultural use patterns will warrant more
      research. More botanical information is also needed to better understand this
      species, including germination, pollination vector and a better understanding of
      the endemic environment of Salvia divinorum. As well there is a gap in the
      genetic knowledge of this species and very little is known about its intra
      species genetics. The terpenes in Salvia divinorum are very well documented,
      however, other classes of constituents in this species warrant further
      investigation and identification. To date, the majority of the pharmacology
      research on Salvia divinorum has focused on the effects of salvinorin A using
      animal models. Published human studies have not reported any harmful effects when
      salvinorin A is administered within the dose range of 0.375-21ug/kg but what are
      the implications when applied to a larger population? More data on the toxicology
      and safety of Salvia divinorum are needed before larger scale clinical trials of
      the potential therapeutic effects of Salvia divinorum and salvinorin A are
      undertaken.

PMID- 24315984
TI  - Truncal rash in adult measles.

PMID- 24315985
TI  - A case of multiple extrahepatic manifestations in a patient with untreated,
      chronic hepatitis C virus infection.
AB  - Chronic hepatitis C virus (HCV) infection is a complex, multi-organ disorder, not
      just limited to the liver. Mixed cryoglobulinemia (MC) type 2 is a common
      extrahepatic complication, in which immunoglobulin complexes deposit in vascular
      endothelium. This in turn creates a diffuse inflammatory reaction, leading to a
      variety of disorders involving multiple systems. We report the rare case of a
      patient with cryoglobulinemia, cutaneous vasculitis, membroproliferative
      glomerulonephritis, and B cell lymphoma with a variant t(6;10) translocation in
      the setting of an untreated, chronic HCV infection. This case highlights the
      challenge associated with diagnosing and managing such a complex presentation. 

PMID- 24315986
TI  - Seeing facial expressions enhances placebo analgesia.
AB  - The strength of the placebo effect is influenced by social contexts and
      individual personality. Although facial expressions provide important contextual
      cues, no study of their influence on the placebo response has been performed
      hitherto. Here we tested (1) whether the observation of facial expressions with
      different emotional content (Neutral, Pain, and Happy) affects the magnitude of
      placebo analgesia, and (2) whether interindividual differences in personality
      traits interact with any modulation of placebo response induced by facial
      expression. Twenty-seven healthy participants underwent classical placebo
      conditioning, and subsequently rated the intensity and unpleasantness of their
      pain experience associated with nociceptive-specific laser pulses delivered to
      the right hand dorsum. On each trial, different visual cues signalled the
      occurrence of a laser stimulus alone or of a laser stimulus accompanied by a sham
      analgesic treatment. In the conditioning period, cues signalling the sham
      treatment were followed by laser stimuli whose intensity was surreptitiously
      lowered. In the test period, either cue was followed by laser stimuli of the same
      intensity. The observation of facial expressions with different emotional content
      enhanced significantly the placebo analgesia. In particular, a significantly
      greater analgesic effect was observed when facial expressions with emotional
      content were presented concomitantly to the nociceptive stimulation. The
      enhancement of placebo analgesia during the observation of facial expressions was
      not correlated with personality traits like empathy and behavioural
      activation/inhibition. These findings quantify for the first time the effect of
      facial expressions on the magnitude of placebo analgesia. 

PMID- 24315987
TI  - Response to letter to the Editor.

PMID- 24315989
TI  - Letter to the editor.

PMID- 24315988
TI  - Differential upregulation in DRG neurons of an alpha2delta-1 splice variant with
      a lower affinity for gabapentin after peripheral sensory nerve injury.
AB  - The alpha2delta-1 protein is an auxiliary subunit of voltage-gated calcium
      channels, critical for neurotransmitter release. It is upregulated in dorsal root
      ganglion (DRG) neurons following sensory nerve injury, and is also the
      therapeutic target of the gabapentinoid drugs, which are efficacious in both
      experimental and human neuropathic pain conditions. alpha2delta-1 has 3 spliced
      regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an
      alternative 3' splice acceptor site. Here we have examined the presence of
      alpha2delta-1 splice variants in DRG neurons, and have found that although the
      main alpha2delta-1 splice variant in DRG is the same as that in brain
      (alpha2delta-1 DeltaA+B+C), there is also another alpha2delta-1 splice variant
      (DeltaA+BDeltaC), which is expressed in DRG neurons and is differentially
      upregulated compared to the main DRG splice variant alpha2delta-1 DeltaA+B+C
      following spinal nerve ligation. Furthermore, this differential upregulation
      occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by
      density gradient separation. The alpha2delta-1 DeltaA+BDeltaC splice variant
      supports CaV2 calcium currents with unaltered properties compared to alpha2delta
      1 DeltaA+B+C, but shows a significantly reduced affinity for gabapentin. This
      variant could therefore play a role in determining the efficacy of gabapentin in
      neuropathic pain. 

PMID- 24315991
TI  - Links between hepatic fibrosis, ductular reaction, and progenitor cell expansion.
AB  - Interactions between cells and their extracellular matrix have been shown to be
      crucial in a wide range of biological processes, including the proliferation and
      differentiation of stem cells. Ductular reactions containing both hepatic
      progenitor cells and extracellular matrix are seen in response to acute severe
      and chronic liver injury. Understanding the molecular mechanisms whereby cell
      matrix interactions regulate liver regeneration may allow novel strategies to
      enhance this process. Both the ductular reaction in humans and hepatic progenitor
      cells in rodent models are closely associated with collagen and laminin, although
      there is still debate about cause and effect. Recent studies have shown a
      requirement for matrix remodeling by matrix metalloproteinases for the
      proliferation of hepatic progenitor cells and suggested defined roles for
      specific matrix components. Understanding the interactions between progenitor
      cells and matrix is critical for the development of novel regenerative and
      antifibrotic therapies. 

PMID- 24315992
TI  - High-definition endoscopy and narrow-band imaging of the bile ducts: new
      possibilities for diagnosis of indeterminate strictures.

PMID- 24315990
TI  - Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia
      after gastric bypass.
AB  - BACKGROUND & AIMS: Postprandial glycemia excursions increase after gastric bypass
      surgery; this effect is even greater among patients with recurrent hypoglycemia.
      These patients also have increased postprandial levels of insulin and glucagon
      like peptide 1 (GLP-1). We performed a clinical trial to determine the role of
      GLP-1 in postprandial glycemia in patients with hyperinsulinemic hypoglycemia
      syndrome after gastric bypass. METHODS: Nine patients with recurrent hypoglycemia
      after gastric bypass (H-GB), 7 patients who were asymptomatic after gastric
      bypass (A-GB), and 8 healthy control subjects underwent a mixed-meal tolerance
      test (350 kcal) using a dual glucose tracer method on 2 separate days. On 1 day
      they received continuous infusion of the GLP-1 receptor antagonist exendin (9-39)
      (Ex-9), and on the other day they received a saline control. Glucose kinetics and
      islet and gut hormone responses were measured before and after the meal. RESULTS:
      Infusion of Ex-9 corrected hypoglycemia in all patients with H-GB. The reduction
      in postprandial insulin secretion by Ex-9 was greater in the H-GB group than in
      the other groups (H-GB, 50% +/- 8%; A-GB, 13% +/- 10%; controls, 14% +/- 10%) (P
      < .05). The meal-derived glucose appearance was significantly greater in subjects
      who had undergone gastric bypass compared to the controls and in the H-GB group
      compared to the A-GB group. Ex-9 shortened the time to reach peak meal-derived
      glucose appearance in all groups without a significant effect on overall glucose
      flux. Postprandial glucagon levels were higher among patients who had undergone
      gastric bypass than controls and increased with administration of Ex-9.
      CONCLUSIONS: Hypoglycemia after gastric bypass can be corrected by administration
      of a GLP-1 receptor antagonist, which might be used to treat this disorder. These
      findings are consistent with reports that increased GLP-1 activity contributes to
      hypoglycemia after gastric bypass. ClinicalTrials.gov, Number: NCT01803451.

PMID- 24315993
TI  - Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary
      transdifferentiation in zebrafish.
AB  - BACKGROUND & AIMS: The liver has high regenerative capacity, but it is not clear
      whether most biliary cells (particularly larger cholangiocytes)
      transdifferentiate into hepatocytes in regenerating liver. We investigated how
      this process might contribute to liver regeneration in zebrafish. METHODS:
      Zebrafish transgenic lines were generated using the standard I-SceI meganuclease
      transgenesis technique. Hepatocytes of the Tg(lfabp:mCherry-NTR)(cq2) animals
      were ablated by the administration of metronidazole. We investigated
      transdifferentiation of biliary cells to hepatocytes and expression of markers
      using whole mount antibody staining, fluorescent in situ hybridization, and
      Cre/loxP-based genetic lineage tracing analyses. The role of biliary cells in
      hepatocyte regeneration was explored using zebrafish larvae with defects in
      biliary cell development. RESULTS: After extreme loss of hepatocytes, nearly all
      the biliary cells steadily lost their tubular morphology, proliferated, and
      expressed hepatocyte-specific markers. Cre/loxP-based inducible lineage tracing
      showed that new hepatocytes mainly arose from transdifferentiation of biliary
      cells; this process required Notch signaling and, in turn, activation of Sox9b in
      cholangiocytes. Activation of early endoderm and hepatoblast markers in most of
      the cholangiocytes indicated that biliary transdifferentiation includes a step of
      dedifferentiation into a bipotential intermediate. Defects in development of
      biliary cells impaired hepatocyte regeneration. CONCLUSIONS: Using our zebrafish
      liver regeneration model, we found that biliary cells can transdifferentiate into
      hepatocytes and are the major contributors to hepatocyte regeneration after
      extreme hepatocyte loss.

PMID- 24315994
TI  - TIM-4 glycoprotein-mediated degradation of dying tumor cells by autophagy leads
      to reduced antigen presentation and increased immune tolerance.
AB  - Phagocytosis of apoptotic cells by myeloid cells has been implicated in the
      maintenance of immune homeostasis. In this study, we found that T cell
      immunoglobulin- and mucin domain-containing molecule-4 (TIM-4) repressed tumor
      specific immunity triggered by chemotherapy-induced tumor cell death. TIM-4 was
      found to be highly expressed on tumor-associated myeloid cells such as
      macrophages (TAMs) and dendritic cells (TADCs) and danger-associated molecular
      patterns (DAMPs) released from chemotherapy-damaged tumor cells induced TIM-4 on
      tumor-associated myeloid cells recruited from bone marrow-derived precursors. TIM
      4 directly interacted with AMPKalpha1 and activated autophagy-mediated
      degradation of ingested tumors, leading to reduced antigen presentation and
      impaired CTL responses. Consistently, blockade of the TIM-4-AMPKalpha1-autophagy
      pathway augmented the antitumor effect of chemotherapeutics by enhancing tumor
      specific CTL responses. Our finding provides insight into the immune tolerance
      mediated by phagocytosis of dying cells, and targeting of the TIM-4-AMPKalpha1
      interaction constitutes a unique strategy for augmenting antitumor immunity and
      improving cancer chemotherapy.

PMID- 24315995
TI  - FoxP3 acts as a cotranscription factor with STAT3 in tumor-induced regulatory T
      cells.
AB  - FoxP3, a lineage-specification factor, executes its multiple activities mostly
      through transcriptional regulation of target genes. We identified an interleukin
      10 (IL-10)-producing FoxP3(+) T regulatory cell population that contributes to IL
      10-dependent type 2 cytokine bias in breast-cancer patients. Although genetic
      ablation of FOXP3 inhibited IL10 transcription, genome-wide analysis ruled out
      its role as a transcription factor for IL10. In-depth analysis revealed that
      histone acetyl transterase-1, in association with FoxP3, modified the IL10
      promoter epigenetically, making a space for docking STAT3-FoxP3 complexes. A
      predictive docking module with target-receptor specificity, along with exon
      deletion and site-directed mutagenesis studies, showed that STAT3 binds through
      its N-terminal floppy domain to the exon 2 beta sheet region of FoxP3 to form
      STAT3-FoxP3 complexes. Such cotranscriptional activity of FoxP3 extended to other
      STAT3-target genes that lack FoxP3-binding sites. These results suggest a
      function of FoxP3, where, failing to achieve direct promoter occupancy, FoxP3
      promotes transcription in association with the locus-specific transcription
      factor STAT3.

PMID- 24315996
TI  - The inhibitory receptor BTLA controls gammadelta T cell homeostasis and
      inflammatory responses.
AB  - gammadelta T cells rapidly secrete inflammatory cytokines at barrier sites that
      aid in protection from pathogens, but mechanisms limiting inflammatory damage
      remain unclear. We found that retinoid-related orphan receptor gamma-t
      (RORgammat) and interleukin-7 (IL-7) influence gammadelta T cell homeostasis and
      function by regulating expression of the inhibitory receptor, B and T lymphocyte
      attenuator (BTLA). The transcription factor RORgammat, via its activating
      function-2 domain, repressed Btla transcription, whereas IL-7 increased BTLA
      levels on the cell surface. BTLA expression limited gammadelta T cell numbers and
      sustained normal gammadelta T cell subset frequencies by restricting IL-7
      responsiveness and expansion of the CD27(-)RORgammat(+) population. BTLA also
      negatively regulated IL-17 and TNF production in CD27(-) gammadelta T cells.
      Consequently, BTLA-deficient mice exhibit enhanced disease in a gammadelta T cell
      dependent model of dermatitis, whereas BTLA agonism reduced inflammation.
      Therefore, by coordinating expression of BTLA, RORgammat and IL-7 balance
      suppressive and activation stimuli to regulate gammadelta T cell homeostasis and
      inflammatory responses.

PMID- 24315997
TI  - Intracellular complement activation sustains T cell homeostasis and mediates
      effector differentiation.
AB  - Complement is viewed as a critical serum-operative component of innate immunity,
      with processing of its key component, C3, into activation fragments C3a and C3b
      confined to the extracellular space. We report here that C3 activation also
      occurred intracellularly. We found that the T cell-expressed protease cathepsin L
      (CTSL) processed C3 into biologically active C3a and C3b. Resting T cells
      contained stores of endosomal and lysosomal C3 and CTSL and substantial amounts
      of CTSL-generated C3a. While "tonic" intracellular C3a generation was required
      for homeostatic T cell survival, shuttling of this intracellular C3-activation
      system to the cell surface upon T cell stimulation induced autocrine
      proinflammatory cytokine production. Furthermore, T cells from patients with
      autoimmune arthritis demonstrated hyperactive intracellular complement activation
      and interferon-gamma production and CTSL inhibition corrected this deregulated
      phenotype. Importantly, intracellular C3a was observed in all examined cell
      populations, suggesting that intracellular complement activation might be of
      broad physiological significance.

PMID- 24315999
TI  - Atypical surface behavior of ceramides with nonhydroxy and 2-hydroxy very long
      chain (C28-C32) PUFAs.
AB  - Unique species of ceramide (Cer) with very-long-chain polyunsaturated fatty acid
      (VLCPUFA), mainly 28-32 carbon atoms, 4-5 double bonds, in nonhydroxy and 2
      hydroxy forms (n-V Cer and h-V Cer, respectively), are generated in rat
      spermatozoa from the corresponding sphingomyelins during the acrosomal reaction.
      The aim of this study was to determine the properties of these sperm-distinctive
      ceramides in Langmuir monolayers. Individual Cer species were isolated by HPLC
      and subjected to analysis of surface pressure, surface potential, and Brewster
      angle microscopy (BAM) as a function of molecular packing. In comparison with
      known species of Cer, n-V Cer and h-V Cer species showed much larger mean
      molecular areas and increased molecular dipole moments in liquid expanded phases,
      which suggest bending and partial hydration of the double bonded portion of the
      VLCPUFA. The presence of the 2-hydoxyl group induced a closer molecular packing
      in h-V Cer than in their chain-matched n-V Cer. In addition, all these Cer
      species showed liquid-expanded to liquid-condensed transitions at room
      temperature. Existence of domain segregation was confirmed by BAM. Additionally,
      thermodynamic analysis suggests a phase transition close to the physiological
      temperature for VLCPUFA-Cers if organized as bulk dispersions.

PMID- 24315998
TI  - T cell exit from quiescence and differentiation into Th2 cells depend on Raptor
      mTORC1-mediated metabolic reprogramming.
AB  - Naive T cells respond to antigen stimulation by exiting from quiescence and
      initiating clonal expansion and functional differentiation, but the control
      mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic
      reprogramming is a central determinant of this transitional process. Loss of
      Raptor abrogated T cell priming and T helper 2 (Th2) cell differentiation,
      although Raptor function is less important for continuous proliferation of
      actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells
      including glycolysis, lipid synthesis, and oxidative phosphorylation to mediate
      antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism
      to the initiation of Th2 cell differentiation by orchestrating cytokine receptor
      expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T
      cell receptor and CD28 costimulatory signals in antigen-stimulated T cells. Our
      studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent
      metabolic reprogramming to quiescence exit, and this in turn coordinates
      lymphocyte activation and fate decisions in adaptive immunity.

PMID- 24316000
TI  - Ca(2+) modulating alpha-synuclein membrane transient interactions revealed by
      solution NMR spectroscopy.
AB  - alpha-Synuclein is involved in Parkinson's disease and its interaction with cell
      membrane is crucial to its pathological and physiological functions. Membrane
      properties, such as curvature and lipid composition, have been shown to affect
      the interactions by various techniques, but ion effects on alpha-synuclein
      membrane interactions remain elusive. Ca(2+) dynamic fluctuation in neurons plays
      important roles in the onset of Parkinson's disease and its influx is considered
      as one of the reasons to cause cell death. Using solution Nuclear Magnetic
      Resonance (NMR) spectroscopy, here we show that Ca(2+) can modulate alpha
      synuclein membrane interactions through competitive binding to anionic lipids,
      resulting in dissociation of alpha-synuclein from membranes. These results
      suggest a negative modulatory effect of Ca(2+) on membrane mediated normal
      function of alpha-synuclein, which may provide a clue, to their dysfunction in
      neurodegenerative disease. 

PMID- 24316001
TI  - Are movies with tobacco, alcohol, drugs, sex, and violence rated for youth? A
      comparison of rating systems in Argentina, Brazil, Mexico, and the United States.
AB  - BACKGROUND: This study aimed to determine between-country differences and changes
      over time in the portrayal of youth risk behaviors in films rated for youth in
      Argentina, Brazil, Mexico and the United States. METHODS: Content and ratings
      were analyzed for 362 films that were popular across all four countries from 2002
      to 2009. Country-specific ratings were classified as either youth or adult, and
      Generalized Estimating Equations were used to determine between-country
      differences in the presence of tobacco, alcohol, drugs, sexual content, and
      violence in youth-rated films. Within-country differences in this content over
      time were also assessed, comparing films released from 2002 to 2005 with those
      released from 2006 to 2009. RESULTS: In the US, films rated for youth were less
      likely to contain all five risk behaviors than in youth-rated films in Argentina,
      Brazil, and, when the "15 and older" rating was considered a youth rating, in
      Mexico. All three Latin American countries "downrated" films that received an
      adult rating in the US. Nevertheless, tobacco and drug use in youth-rated films
      declined over time in all countries, whereas moderate to extreme alcohol use and
      violence involving children or youth increased in all countries. CONCLUSIONS:
      Tobacco and drug use have declined in popular US films, but these behaviors are
      still prevalent in films rated for youth across the Americas. The apparent
      success of advocacy efforts to reduce tobacco and other drugs in films suggests
      that similar efforts be directed to reduce alcohol portrayals.

PMID- 24316002
TI  - Contextualizing gender differences and methamphetamine use with HIV prevalence
      within a South African community.
AB  - BACKGROUND: This study was conducted in a large Black African township outside of
      Cape Town, South Africa, where HIV infection has been endemic at extremely high
      levels for years. Problems associated with high HIV prevalence are compounded by
      gender inequality and high rates of gender-based violence exacerbated by heavy
      alcohol use and increasing methamphetamine use. METHODS: Informal drinking
      establishments (known as shebeens) were geocoded and mapped. Based on visual
      examination, we identified 36 neighbourhoods, each of which contained between
      three to seven drinking venues clustered together. Neighbourhoods were separated
      from each other by at least 200m. We randomly selected 30 of the 36
      neighbourhoods. Outreach workers screened males in shebeens and screened their
      female partners. This analysis includes 580 study participants recruited from 30
      neighbourhoods between 2010 and 2012. All participants completed a baseline
      questionnaire that included individual-level, couple-level, and neighbourhood
      level measures of alcohol and other drug use, HIV infection, and HIV risk
      behaviours. Multilevel fixed effects regression analyses stratified by gender
      were conducted to examine correlates of HIV infection. RESULTS: Women were twice
      as likely as men to be HIV infected, yet they reported fewer sex partners.
      Neighbourhood prevalence of HIV was correlated with greater likelihood of HIV
      infection among women, but not men. Neighbourhood methamphetamine use was
      marginally associated with HIV among women but not among men. At the individual
      level, heavy alcohol use was marginally associated with HIV infection among men
      but not among women. Having an HIV positive partner was the strongest correlate
      of being HIV positive among both men and women. CONCLUSION: Findings from this
      study underscore the need for policy makers to direct scarce resources to the
      communities, places within communities, and populations, especially vulnerable
      women, where the impact on HIV prevention and onward transmission will be
      greatest.

PMID- 24316003
TI  - Limb patterning: from signaling gradients to molecular oscillations.
AB  - The developing forelimb is patterned along the proximal-distal and anterior
      posterior axes by opposing gradients of retinoic acid and fibroblast growth
      factors and by graded sonic hedgehog signaling, respectively. However, how
      coordinated patterning along both axes is accomplished with temporal precision
      remains unknown. The limb molecular oscillator hairy2 was recently shown to be a
      direct readout of the combined signaling activities of retinoic acid, fibroblast
      growth factor and sonic hedgehog in the limb mesenchyme. Herein, an integrated
      time-space model is presented to conciliate the progress zone and two-signal
      models for limb patterning. We propose that the limb clock may allow temporal
      information to be decoded into positional information when the distance between
      opposing signaling gradients is no longer sufficient to provide distinct cell
      fate specification. 

PMID- 24316005
TI  - Manual selection of spontaneous activity maps derived from independent component
      analysis: criteria and inter-rater reliability study.
AB  - BACKGROUND: During the last years, many investigations focused on spontaneously
      active cerebral networks such as the default-mode network. A data-driven
      technique, the independent component analysis, allows segregating such
      spontaneous (co-)activity maps (SAM) from noise in functional magnetic resonance
      imaging (fMRI) time series. The inter-rater reliability of manual selection of
      not only the default-mode network but all SAMs remained to be assessed. NEW
      METHOD: The current study was performed on 20 min (400 volumes) fMRI time series
      of 30 healthy participants. SAMs' selection criteria were first established on
      past experience and from the literature. The inter-rater reliability of SAMs vs
      non-SAMs manual selection was then investigated from 250 independent components
      per participant. RESULTS: Inter-rater Kappa coefficient was of 0.89 +/- 0.01 on
      whole analysis, and 0.88 +/- 0.09 on participant per participant analysis.
      COMPARISON WITH EXISTING METHODS: Without focusing on specific and predetermined
      SAMs only, our criteria allow a reliable selection of all SAMs including the
      idiosyncratic networks. CONCLUSIONS: The proposed SAM's selection criteria are
      reliable enough to allow scientific exploration of all SAMs at the single subject
      level.

PMID- 24316004
TI  - GpIbalpha interacts exclusively with exosite II of thrombin.
AB  - Activation of platelets by the serine protease thrombin is a critical event in
      haemostasis. This process involves the binding of thrombin to glycoprotein
      Ibalpha (GpIbalpha) and cleavage of protease-activated receptors (PARs). The N
      terminal extracellular domain of GpIbalpha contains an acidic peptide stretch
      that has been identified as the main thrombin binding site, and both anion
      binding exosites of thrombin have been implicated in GpIbalpha binding, but it
      remains unclear how they are involved. This issue is of critical importance for
      the mechanism of platelet activation by thrombin. If both exosites bind to
      GpIbalpha, thrombin could potentially act as a platelet adhesion molecule or
      receptor dimerisation trigger. Alternatively, if only a single site is involved,
      GpIbalpha may serve as a cofactor for PAR-1 activation by thrombin. To determine
      the involvement of thrombin's two exosites in GpIbalpha binding, we employed the
      complementary methods of mutational analysis, binding studies, X-ray
      crystallography and NMR spectroscopy. Our results indicate that the peptide
      corresponding to the C-terminal portion of GpIbalpha and the entire extracellular
      domain bind exclusively to thrombin's exosite II. The interaction of thrombin
      with GpIbalpha thus serves to recruit thrombin activity to the platelet surface
      while leaving exosite I free for PAR-1 recognition. 

PMID- 24316007
TI  - Peripheral T lymphocyte subset imbalances in children with enterovirus 71-induced
      hand, foot and mouth disease.
AB  - Inflammatory mediators (i.e. cytokines) play a pivotal role in the regulation of
      pathophysiological processes during EV71-induced hand, foot and mouth disease
      (HFMD). Different T cell subsets have distinct cytokine secretion profiles, and
      alteration in the T cell subsets frequency (imbalance) during infection leads to
      changed cytokine patterns. However, the effects of EV71 infection on T cell
      subsets were not clear. The objective of this study was to determine whether EV71
      induced HFMD can be explained by the emergence of particular T-cell subsets (Th1,
      Th2, Tc1, Tc2, Th17, Tc17 and Treg cells) and the cytokine they produced (IFN
      gamma, IL-4, IL-17A and TGF-beta1), as well as distinct responses to EV71
      infection. We found that when compared to the control group, the percentage of
      Th1 and Tc1 cells was significantly higher in mild and severe HFMD group. Similar
      results were found in the Th1/Th2 ratio and IFN-gamma levels. On the other hand,
      the percentage of Th17 cells and IL-17A levels were the highest in severe HFMD
      cases, and lowest in controls. Similar trend was also found for the Th17/Treg
      cell ratio. An optimal cutoff value of 2.15% for Th17 cell and 6.72 pg/ml for IL
      17A provided a discriminatory value for differentiating the severity of HFMD
      cases by receiver operating characteristic curve analyses. These findings reveal
      that the Th1/Th2 and Th17/Treg imbalance exist in HFMD patients, suggesting their
      involvement in the pathogenesis of EV71 infection, which may have potential value
      as biomarkers.

PMID- 24316006
TI  - Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke
      induced DNA damage and cytotoxicity.
AB  - Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the
      oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS).
      Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not
      been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels
      showed the greatest induction in response to CS extract (CSE) exposure of primary
      human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was
      accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized
      HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced
      cytotoxicity and DNA damage (gammaH2AX) were evaluated in cultured immortalized
      HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated
      gammaH2AX. SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity
      and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the
      availability of ALDH3A1 is important for cell survival against CSE in HBECs. 

PMID- 24316008
TI  - The nuclear protein Sam68 is redistributed to the cytoplasm and is involved in
      PI3K/Akt activation during EV71 infection.
AB  - Nuclear proteins can be triggered to be redistributed to the cytoplasm to assist
      with EV71 virus replication. This process is frequently involved in cellular
      signal transduction upon virus infection. In this study, we have demonstrated
      that a new nuclear protein, 68-kDa Src-associated in mitosis protein (Sam68), was
      translocated to the cytoplasm and was co-localized with EV71 during virus
      infection. Confocal microscopy and subcellular fractionation assay confirmed that
      virus 3C protease triggered the redistribution of Sam68 to the cytoplasm.
      Knockdown of Sam68 expression using ShRNA significantly inhibited virus
      replication, suggesting that Sam68 may be a host factor involved in EV71 life
      cycle. In addition, EV71-induced Akt phosphorylation involved a PI3K-dependent
      mechanism. Sam68 is known to be an upstream regulator of PI3K and our
      immunoprecipitation studies confirmed that Sam68 interacted directly with the p85
      regulatory subunit of PI3K and mediated PI3K/Akt activation during EV71
      infection. On the contrary, silencing of Sam68 dramatically abrogated Akt
      phosphorylation. These data, plus the fact that Sam68 is known to be a signaling
      adaptor protein, indicated that Sam68 is a signal molecule with a functional role
      in the PI3K/Akt signal pathway during EV71 infection. 

PMID- 24316009
TI  - Contrasting effect of silicon on iron, zinc and manganese status and accumulation
      of metal-mobilizing compounds in micronutrient-deficient cucumber.
AB  - Although the beneficial role of silicon (Si) in alleviation of abiotic stress is
      well established, little is known of the relevance of Si nutrition under
      microelement deficiency. The aim of our work was to investigate the physiological
      role of Si in relation to micronutrient (Fe, Zn and Mn) deficiencies in cucumber
      (Cucumis sativus L.). Cucumber (cv. Semkross) plants were grown hydroponically in
      a complete nutrient solution (control) and in nutrient solutions free from Fe, Zn
      or Mn, with or without Si supply. Plant tissue concentrations of microelements,
      organic acids and phenolics were measured. Si supply effectively mitigated the
      symptoms of Fe deficiency, but only in part, the symptoms of Zn- or Mn
      deficiency. Leaf Fe concentration significantly increased in plants deprived of
      Fe but treated with Si, whereas the concentrations of other microelements were
      not affected by Si supply. The effects of Si supply in increasing accumulation of
      both organic acids and phenolic compounds in cucumber tissues were exclusively
      related to Fe nutrition. Enhancement of Fe distribution towards apical shoot
      parts, along with the tissue accumulation of Fe-mobilizing compounds such as
      citrate (in leaves and roots) or cathechin (in roots) appears to be the major
      alleviating effect of Si. Si nutrition, however, was without effect on the
      mobility and tissue distribution of either Zn or Mn. 

PMID- 24316010
TI  - Stress inducible proteomic changes in Capsicum annuum leaves.
AB  - Herbivore attack induces defense responses in plants, activating several
      signaling cascades. As a result, molecules deterrent to the herbivores are
      produced and accumulated in plants. Expression of defense mechanism/traits
      requires reorganization of the plant metabolism, redirecting the resources
      otherwise meant for growth. In the present work, protein profile of Capsicum
      annuum leaves was examined after herbivore attack/induction. Majority of proteins
      identified as differentially accumulated, were having roles in redox metabolism
      and photosynthesis. For example, superoxide dismutase and NADP oxidoreductase
      were upregulated by 10- and 6-fold while carbonic anhydrase and fructose-1,6
      bisphosphatase were downregulated by 9- and 4-fold, respectively. Also,
      superoxide dismutase, NADPH quinone oxidoreductase and NADP dependent isocitrate
      dehydrogenase transcripts showed a higher accumulation in induced leaf tissues at
      early time points. In general, proteins having role in defense and damage repair
      were upregulated while those involved in photosynthesis appeared downregulated.
      Thus metabolic reconfiguration to balance defense and tolerance was evident in
      the stress-induced leaves. 

PMID- 24316011
TI  - Hydrogen peroxide regulated photosynthesis in C4-pepc transgenic rice.
AB  - In this study, we investigated the photosynthetic physiological basis in 'PC'
      transgenic rice (Oryza sativa L.), showing high-level expression of the gene
      encoding C4 phosphoenolpyruvate carboxylase (pepc), by hydrogen peroxide (H2O2).
      The C4-PEPC gene (pepc) from maize in the transgenic rice plants was checked by
      PCR. Comparison of yield components and photosynthetic indices between PC and
      untransformed wild-type (WT) plants indicated that increased yield in PC was
      associated with higher net photosynthetic rate and higher activities of
      phosphoenolpyruvate carboxylase (PEPC). Both PC and WT plants were treated with 1
      mmol L(-1) abscisic acid (ABA), 0.04% 1-butanol (BA), 2 mmol L(-1) neomycin (NS),
      or 2 mmol L(-1) diphenyleneiodonium chloride (DPI) to investigate the
      relationship between photosynthesis and levels of H2O2 and phosphatidic acid. In
      both PC and WT, ABA induced H2O2 generation and simultaneous decrease in stomatal
      conductance (g(s)). PC plants treated with BA showed decreased H2O2 content and
      strongly increased g(s) within 2 h of treatment. Similar results were observed in
      response to DPI treatment in PC. However, WT did not observe the decrease of H2O2
      during the treatments of BA and DPI. The reduced H2O2 content in PC caused by BA
      treatment differed to that induced by DPI because BA did not inhibit NADPH
      oxidase activities. While BA induced a larger PEPC activity in PC, and higher
      catalase activity as well. These results indicated that the regulation of
      endogenous H2O2 metabolism of PC could be helpful for enhancing photosynthetic
      capability.

PMID- 24316012
TI  - Innate antiviral signalling in the central nervous system.
AB  - The innate immune system mediates protection against neurotropic viruses capable
      of infecting the central nervous system (CNS). Neurotropic viruses include herpes
      simplex virus (HSV), West Nile virus (WNV), rabies virus, La Crosse virus, and
      poliovirus. Viral infection triggers activation of pattern recognition receptors
      (PRRs) such as Toll-like receptors (TLRs), retinoic acid-inducible gene 1 (RIG-I)
      like receptors (RLRs), nucleotide-binding oligomerization domain (NOD)-like
      receptors (NLRs), and cytosolic DNA sensors. Although originally characterised in
      peripheral immune cells, emerging evidence points to important roles for these
      PRRs in cells of the CNS. Here, we review recent advances in our understanding of
      the mechanisms by which these PRRs provide protection against neurotropic
      viruses, and discuss instances in which these responses become detrimental and
      cause immunopathology in the CNS. 

PMID- 24316013
TI  - 2,4-Dichlorophenol induces global DNA hypermethylation through the increase of S
      adenosylmethionine and the upregulation of DNMTs mRNA in the liver of goldfish
      Carassius auratus.
AB  - Altered DNA methylation is associated with changes in gene expression, signal
      transduction and stress response after exposure to a wide range of exogenous
      compounds, and abnormal methylation is a major toxic effect induced by chemicals
      such as benzene and phenols. 2,4-Dichlorophenol (2,4-DCP), a derivative of
      phenol, has been classified as a priority pollutant by the US EPA due to its
      toxic effects on aquatic organisms. However, the effect of 2,4-DCP on DNA
      methylation and its potential mechanism in fish are rarely understood. The
      present study aims to figure out whether 2,4-DCP could impact DNA methylation and
      explore its potential mechanisms by measuring the global DNA methylation levels,
      S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) contents, the mRNA
      expression of DNA methyltransferase1 (DNMT1) and DNA methyltransferase3 (DNMT3)
      in the liver of goldfish Carassius auratus. DNA methylation levels were analyzed
      using high performance liquid chromatography (HPLC) and MspI/HpaII ethidium
      bromide assay, SAM and SAH contents were determined by HPLC, the mRNA expression
      of DNMT1 and DNMT3 was measured by quantitative-PCR (qPCR). The results showed
      that 2,4-DCP caused global DNA hypermethylation, elevated the methylation levels
      of CpG islands, increased the SAM and SAH contents, decreased the SAM/SAH ratio,
      and upregulated the mRNA expression of DNMT1 and DNMT3, while depletion of SAM
      with Na2SeO3 and inhibition of DNMTs activity with 5-aza-2'-deoxycytidine (5AdC)
      impaired 2,4-DCP-induced global DNA hypermethylation, suggesting that the
      increase of SAM contents and upregulation of the mRNA expression of DNMT1 and
      DNMT3 may play important roles in 2,4-DCP-induced global DNA hypermethylation
      process. Our report is the first one to show that short-term 2,4-DCP exposure
      caused the global DNA hypermethylation via altered SAM level and DNMTs expression
      in fish. 

PMID- 24316014
TI  - Evaluation of the rapid RIDAQUICK Campylobacter(r) test in a general hospital.
AB  - The study objective was to evaluate the effectiveness of the new rapid
      immunochromatographic test RIDAQUICK Campylobacter(r) (r-biopharm AG, Darmstadt,
      Germany) for the qualitative detection of Campylobacter antigens in pathologic
      feces from primary and specialist care patients. Three hundred feces samples were
      studied from patients with diarrhea, 50.6% from adults and 49.4% from children,
      which were received by our microbiology laboratory for coproculture.
      Campylobacter culture results, with or without PCR data, served as reference
      values for the comparative evaluation of RIDAQUICK Campylobacter(r) findings.
      Campylobacter was detected in 12.3% of samples. The diagnostic accuracy values of
      the RidaQuick Campylobacter(r) versus culture were: sensitivity of 87%,
      specificity of 97%, and positive and negative predictive values of 77% and 98%,
      respectively. RIDAQUICK Campylobacter(r) is a rapid test for the diagnosis of
      enteritis due to Campylobacter and could be an option for the clinical diagnosis
      of one of the main causes of bacterial enteritis in resource-limited settings. 

PMID- 24316015
TI  - Improving the management of candidemia through antimicrobial stewardship
      interventions.
AB  - Candidemia is associated with significant morbidity, mortality, and hospital
      cost. We conducted a quasi-experimental study to evaluate the impact of an
      Antimicrobial Stewardship Program (ASP) pharmacist's interventions on time to
      effective antifungal therapy, in-hospital mortality, infection-related length of
      stay (LOS), and costs in patients with candidemia. Patients in 2008 (pre
      intervention, n = 85) were compared to those in 2010 (post-intervention, n = 88).
      Time to effective therapy was significantly faster (median 13.5 versus 1.3 hours,
      P = 0.04) and was administered to more patients in the post-intervention group
      [67 (88%) versus 80 (99%), P = 0.008]. There was no significant difference in in
      hospital mortality [16 (19%) versus 26 (30%) patients, P = 0.11], infection
      related LOS [10 (7-15.5) versus 11 (7-17) days, P = 0.68], or hospital costs
      during candidemia [$25,697 (15,645-42,870) versus $31,457 ($16,399-83,649), P =
      0.25]. ASP pharmacist interventions standardized and improved the quality of care
      of patients with candidemia. 

PMID- 24316016
TI  - Diagnosis of venous access port colonization requires cultures from multiple
      sites: should guidelines be amended?
AB  - Data on microbiological management of withdrawn venous access ports (VAPs) are
      scarce. The aim of our study was to assess the validity of Gram stain and culture
      performed on VAPs to detect colonization and VAP-related bloodstream infection
      (VAP-RBSI). We prospectively performed cultures of the following: catheter tip
      (roll-plate and sonication), port content aspirate before and after sonication,
      port sonication fluid (PSF), and port internal surface biofilm (ISB). The gold
      standard of VAP colonization was positivity of at least 1 of the cultures
      mentioned above. We collected 223 VAPs in which no single culture had validity
      values reliable enough to predict colonization and VAP-RBSI. The best validity
      values were those obtained when cultures of catheter tip (roll-plate), PSF, and
      port ISB were combined. Cultures from several areas on the VAP are necessary to
      ensure suitable assessment of colonization and VAP-RBSI. 

PMID- 24316017
TI  - Clinical features of West Nile virus epidemic in Dallas, Texas, 2012.
AB  - In 2012, Texas has reported the highest number of West Nile virus (WNV) cases in
      the United States to the Centers for Disease Control and Prevention. In this
      report, we conducted a retrospective chart review of 57 patients with WNV disease
      and analyzed the clinical features of these patients. Our results revealed that
      25 (44%) patients were diagnosed with West Nile fever and 32 (56%) with West Nile
      neuroinvasive disease (WNND). The median age for patients with WNND was 54.5
      years, and those with encephalitis were more likely to be >60 years old. Pre
      existing conditions such as hypertension and diabetes were more frequent in
      patients with WNND. Testing both serum and cerebrospinal fluid (CSF) for
      antibodies diagnosed more cases of WNND than just testing serum or CSF alone. The
      increasing number of WNV cases during this epidemic highlights the need to
      increase efforts to control mosquito populations and educate the general public. 

PMID- 24316018
TI  - An inexact study design produced misleading conclusions: to perform operative
      procedures in an optimized local atmosphere: CAn it reduce post-operative
      adhesion formation? de Vries A, Marvik R, Kuhry E. [Int J Surg 11 (2013) 1118
      1122].

PMID- 24316019
TI  - Virtual reality simulation training in Otolaryngology.
AB  - OBJECTIVE: To conduct a systematic review of the validity data for the virtual
      reality surgical simulator platforms available in Otolaryngology. DATA SOURCES:
      Ovid and Embase databases searched July 13, 2013. REVIEW METHODS: Four hundred
      and nine abstracts were independently reviewed by 2 authors. Thirty-six articles
      which fulfilled the search criteria were retrieved and viewed in full text. These
      articles were assessed for quantitative data on at least one aspect of face,
      content, construct or predictive validity. Papers were stratified by simulator,
      sub-specialty and further classified by the validation method used. RESULTS:
      There were 21 articles reporting applications for temporal bone surgery (n = 12),
      endoscopic sinus surgery (n = 6) and myringotomy (n = 3). Four different
      simulator platforms were validated for temporal bone surgery and two for each of
      the other surgical applications. Face/content validation represented the most
      frequent study type (9/21). Construct validation studies performed on temporal
      bone and endoscopic sinus surgery simulators showed that performance measures
      reliably discriminated between different experience levels. Simulation training
      improved cadaver temporal bone dissection skills and operating room performance
      in sinus surgery. CONCLUSION: Several simulator platforms particularly in
      temporal bone surgery and endoscopic sinus surgery are worthy of incorporation
      into training programmes. Standardised metrics are necessary to guide curriculum
      development in Otolaryngology.

PMID- 24316021
TI  - The 100 most cited papers in foot and ankle surgery.
AB  - BACKGROUND: The number of citations of a paper gives an indication of an
      article's merit and importance within a medical specialty. We identify and
      analyse the 100 most cited papers in foot and ankle surgery. METHOD: The Science
      Citation Index Expanded was searched for citations in 15 respected journals
      containing foot and ankle articles. Papers were analysed for subject, authorship,
      institution, country and year of publication. The average yearly citation was
      compared to total number of citations. RESULTS: 3501 foot and ankle papers were
      returned. The maximum number of citations was 1084 and the mean was 104. The top
      100 papers were published between 1979 and 2007, with the majority published in
      the last decade. The ankle was the most important anatomical region discussed,
      and basic science and degenerative disease were popular topics. We found a large
      discrepancy between the total number of citations with average yearly citation.
      CONCLUSION: Foot and ankle surgery is a young and rapidly developing sub
      specialty within orthopaedics. Recently there has been a significant increase in
      influential papers published. Certain topics are popular indicating their
      importance within the field. This study highlights important papers in foot and
      ankle surgery giving an insight into readership.

PMID- 24316020
TI  - Surface plasmon resonance measurements of plasma antibody avidity during primary
      and secondary responses to anthrax protective antigen.
AB  - Establishment of humoral immunity against pathogens is dependent on events that
      occur in the germinal center and the subsequent induction of high-affinity
      neutralizing antibodies. Quantitative assays that allow monitoring of affinity
      maturation and duration of antibody responses can provide useful information
      regarding the efficacy of vaccines and adjuvants. Using an anthrax protective
      antigen (rPA) and alum model antigen/adjuvant system, we describe a methodology
      for monitoring antigen-specific serum antibody concentration and avidity by
      surface plasmon resonance during primary and secondary immune responses. Our
      analyses showed that following a priming dose in mice, rPA-specific antibody
      concentration and avidity increases over time and reaches a maximal response in
      about six weeks, but gradually declines in the absence of antigenic boost.
      Germinal center reactions were observed early with maximal development achieved
      during the primary response, which coincided with peak antibody avidity responses
      to primary immunization. Boosting with antigen resulted in a rapid increase in
      rPA-specific antibody concentration and five-fold increase in avidity, which was
      not dependent on sustained GC development. The described methodology couples
      surface plasmon resonance-based plasma avidity measurements with germinal center
      analysis and provides a novel way to monitor humoral responses that can play a
      role in facilitating vaccine and adjuvant development. 

PMID- 24316022
TI  - Toward a common therapeutic framework in castration-resistant prostate cancer: a
      model for urologic oncology and medical oncology interaction.
AB  - BACKGROUND: The rapid evolution of palliative therapeutic choices in the last few
      years for patients with advanced castration-resistant prostate cancer (CRPC) has
      resulted in a dilemma currently troubling a few other epithelial malignancies:
      which systemic agent to choose and at what time? In addition, which specialty
      specifically directs the delivery of such care--Urology or Medical Oncology--has
      not been clearly established. APPROACH: Recognizing the lack of consensus, we
      propose a framework for Urology and Medical Oncology interactions that is founded
      on models that have succeeded in the past. CONCLUSION: This approach aims to
      focus the care on the patient with CRPC rather than on his physicians and
      promises to improve patient outcomes in this disease state.

PMID- 24316023
TI  - Connections in pharmacology: innovation serving translational medicine.
AB  - There is a paucity of molecules that progress through the drug development
      pipeline, making the drug discovery process expensive and frustrating. Innovative
      approaches to drug development are therefore required to maximise opportunities.
      Strategies such as the Connectivity Map (CMap), which compares >7000 gene
      expression signatures generated from more than 1000 drugs, can produce
      associations between currently unrelated therapeutics, unveiling new mechanisms
      of action and favouring drug repositioning. Here, we discuss these opportunities
      that could aid the drug development process and propose rigorous publication of
      'omics data with open access and data sharing. We, pharmacologists of the third
      millennium, must aim towards maximising knowledge in an unbiased and cost
      effective manner, to deliver new drugs for the global benefit of patients.

PMID- 24316024
TI  - Secreted frizzled related proteins: Implications in cancers.
AB  - The Wnt (wingless-type) signaling pathway plays an important role in embryonic
      development, tissue homeostasis, and tumor progression becaluse of its effect on
      cell proliferation, migration, and differentiation. Secreted frizzled-related
      proteins (SFRPs) are extracellular inhibitors of Wnt signaling that act by
      binding directly to Wnt ligands or to Frizzled receptors. In recent years,
      aberrant expression of SFRPs has been reported to be associated with numerous
      cancers. As gene expression of SFRP members is often lost through promoter
      hypermethylation, inhibition of methylation through the use of epigenetic
      modifying agents could renew the expression of SFRP members and further
      antagonize deleterious Wnt signaling. Several reports have described epigenetic
      silencing of these Wnt signaling antagonists in various human cancers, suggesting
      their possible role as tumor suppressors. SFRP family members thus come across as
      potential tools in combating Wnt-driven tumorigenesis. However, little is known
      about SFRP family members and their role in different cancers. This review
      comprehensively covers all the available information on the role of SFRP
      molecules in various human cancers. 

PMID- 24316025
TI  - Synthesis and biological evaluation of a series of aminoalkyl-tetralones and
      tetralols as dual dopamine/serotonin ligands.
AB  - A series of novel alpha-tetralone and alpha-tetralol derivatives was synthesized,
      and their binding affinities for 5-HT(2A) and D2 receptors, the most important
      targets implicated in the anti-schizophrenia drug action, were evaluated to
      elucidate how substitutions in the aromatic ring of the pharmacophore affect to
      the affinity or selectivity for these receptors. The replacement of the H-7 in
      the tetrahydronaphthalene system by an amino group resulted in privileged 5
      HT(2A) affinity of the 6-fluorobenzo[d]isoxazol derivative 36 and the alcohol 25
      both showing a pK(i) value for 5-HT(2A) higher than 8.3 and good binding
      affinities for D2 receptor leading to a Meltzer's ratio characteristic of an
      atypical antipsychotic profile. Additionally, a small collection of 3
      aminomethyltetralone derivatives was prepared and examined here for their
      affinities and selectivities as 5-HT(2A)/D2 dual ligands. Compound 11 shows the
      best profile with good pKi values for 5-HT(2A) and D2 receptors leading to a
      Meltzer's ratio characteristic of a typical antipsychotic behaviour. These three
      compounds behaved as competitive antagonists of both 5-HT(2A) and D2 receptors,
      and might be promising pharmacological tools for the investigation of the dual
      function of the 5HT(2A)-D2 ligands.

PMID- 24316026
TI  - Frequent plasma cell hepatitis during telaprevir-based triple therapy for
      hepatitis C after liver transplantation.

PMID- 24316027
TI  - Reply to: "Frequent plasma cell hepatitis during telaprevir-based triple therapy
      for hepatitis C after liver transplantation".

PMID- 24316028
TI  - The role of genetic polymorphisms in cytochrome P450 and effects of tuberculosis
      co-treatment on the predictive value of CYP2B6 SNPs and on efavirenz plasma
      levels in adult HIV patients.
AB  - Efavirenz (EFV) exhibits interindividual pharmacokinetic variability caused by
      differences in cytochrome P450 (CYP) expression. Most tuberculosis (TB) drugs
      interact with the CYP metabolizing enzymes, while the clinical validity of
      genotyping in predicting EFV plasma levels in Rwandan subjects is not known. We
      investigated in patients co-infected with human immunodeficiency virus (HIV) and
      TB recruited in Rwanda the effects of 10 SNPs in five drug-metabolizing enzymes
      on EFV plasma levels and treatment response when patients are treated with EFV
      containing therapy alone (n=28) and when combined with rifampicin-based TB
      treatment (n=62), and the validity of genotyping for CYP2B6 single nucleotide
      polymorphisms in predicting supra-therapeutic EFV levels. There was a significant
      difference between CYP1A2 -739T/G and T/T genotypes when patients were treated
      with EFV-containing therapy combined with rifampicin-based TB treatment, but not
      when EFV-containing therapy was alone. CYP2B6 516T/T genotype was associated with
      high EFV levels compared to other CYP2B6 516G>T genotypes in the presence and in
      the absence of rifampicin-based TB treatment. Predictive factors of EFV plasma
      levels in the presence of rifampicin-based TB treatment were CYP2A6 1093G>A,
      CYP2B6 516G>T, and CYP2B6 983T>C accounting for 27%, 43%, and 29% of the total
      variance in EFV levels, respectively. There was a high positive predictive value
      (PPV) (100%) for CYP2B6 516T/T and 983T/T genotypes in predicting EFV plasma
      levels above the therapeutic range, but this PPV decreased in the presence of
      rifampicin-based TB treatment. Rifampicin-based TB treatment was also shown to
      affect EFV plasma levels significantly, but did not affect the significant
      reduction of HIV-RNA copies. These results indicate that genotyping for CYP2B6
      SNPs could be used as a tool in predicting supra-therapeutic EFV plasma levels,
      which could minimize adverse drug events. 

PMID- 24316029
TI  - Inhibition of human cytomegalovirus replication by overexpression of CREB1.
AB  - Expression of the human cytomegalovirus (HCMV) major immediate-early (MIE) genes
      is regulated by a strong enhancer-containing promoter with multiple binding sites
      for various transcription factors, including cyclic AMP response element binding
      protein 1 (CREB1). Here we show that overexpression of CREB1 potently blocked MIE
      transcription and HCMV replication. Surprisingly, CREB1 still exhibited strong
      inhibition of the MIE promoter when all five CREB binding sites within the
      enhancer were mutated, suggesting that CREB1 regulated the MIE gene expression
      indirectly. Promoter deletion analysis and site-directed mutagenesis identified
      the region between -130 and -50 upstream of the transcription start site of the
      MIE gene as the "CREB1 responsive region". Mutations of SP1/3 and NF-kappaB
      binding sites within this region interrupted the inhibitory effect induced by
      CREB1 overexpression. Our findings suggest that overexpression of CREB1 can cause
      repression of HCMV replication and may contribute to the development of new anti
      HCMV strategies. 

PMID- 24316030
TI  - Role of IL28-B polymorphisms in the treatment of chronic hepatitis B HBeAg
      negative patients with peginterferon.
AB  - Interleukin (IL)28-B polymorphism has been related to interferon response in the
      treatment of hepatitis C, but its role in chronic hepatitis B (CHB) therapy is
      still poorly understood. We aimed to investigate the effect of IL28-B
      polymorphisms in the treatment with pegylated-interferon (PEG-IFN) of patients
      with CHB. We retrospectively analyzed 190 patients with chronic hepatitis B e
      antigen (HBeAg) negative, genotype A (22%), B (12%), C (10%), D (33%), E (20%),
      treated with PEG-IFN alfa-2a for 48weeks; genotype analysis was performed for
      IL28-B polymorphisms rs12979860, rs8099917 and rs12980275 according to
      virological, serological and biochemical response. During 2years of follow-up 12
      patients (6.3%) cleared hepatitis B surface antigen (HBsAg) with seroconversion,
      40 (21%) obtained a negative viral load and 104 (54.7%) gained a biochemical
      response. We found a difference of distribution of rs12979860 CC genotype among
      different ethnicity (p=0.013). Rs12979860 CC genotype was significantly
      associated with serological and virological response (p<0.001); rs8099917 TT and
      rs12980275 AA genotypes were mostly related with virological response (p<0.001).
      In multivariate logistic analysis rs12979860 CC was predictive of virological
      response (OR=4.290; CI=1.589-11.580, p=0.004) and serological response
      (OR=10.129; CI=2.440-42.044; p<0.001). Rs8099917 TT was predictive only of
      virological response (OR=3.746, CI=1.235-11.355; p=0.020). The E genotype was a
      negative predictive factor of virological response (OR=0.057; CI=0.014-0.238;
      p<0.001). IL28-B polymorphisms are related to different response in the treatment
      of CHB HBeAg-negative with PEG-IFN, and the E genotype is a novel negative
      predictive factor. 

PMID- 24316031
TI  - Amino acid similarities and divergences in the small surface proteins of genotype
      C hepatitis B viruses between nucleos(t)ide analogue-naive and lamivudine-treated
      patients with chronic hepatitis B.
AB  - Entire C-genotype small hepatitis B surface (SHBs) sequences were isolated from
      139 nucleos(t)ide analogues (NA)-naive and 74 lamivudine (LMV)-treated chronic
      hepatitis B (CHB) patients. The conservation and variability of total 226 amino
      acids (AAs) within the sequences were determined individually, revealing
      significant higher mutant isolate rate and mutation frequency in LMV-treated
      cohort than those in the NA-naive one (P=0.009 and 0.0001, respectively). Three
      absolutely conserved fragments (s16-s19, s176-s181 and s185-s188) and seven
      moderately conserved regions (a few AA sites acquiring increased variability
      after LMV-treatment) were identified. The significant mutation rate increase
      after LMV-treatment occurred primarily in major hydrophilic region (except 'a'
      determinant) and transmembrane domain 3/4, but not in other upstream functional
      regions of SHBs. With little influence on immune escape-associated mutation
      frequencies within 'a' determinant, LMV-monotherapy significantly induced
      classical LMVr-associated mirror changes sE164D/rtV173L, sI195M/rtM204V and
      sW196L/S/rtM204I, as well as non-classical ones sG44E/rtS53N, sT47K/A/rtH55R/Q
      and sW182stop/rtV191I outside 'a' determinant. Interestingly, another newly
      identified truncation mutation sC69stop/rtS78T decreased from 7.91% (11/139) in
      NA-naive cohort to 2.70% (2/74) in LMV-treated one. Altogether, the altered AA
      conservation and diversity in SHBs sequences after LMV-treatment in genotype-C
      HBV infection might shed new insights into how LMV-therapy affects the SHBs
      variant evolution and its antigenicity. 

PMID- 24316032
TI  - Naphthalene-sulfonate inhibitors of human norovirus RNA-dependent RNA-polymerase.
AB  - Noroviruses are members of the Caliciviridae family of positive sense RNA
      viruses. In humans Noroviruses cause rapid onset diarrhea and vomiting. Currently
      Norovirus infection is responsible for 21 million gastroenteritis yearly cases in
      the USA. Nevertheless, despite the obvious public health and socio-economic
      relevance, no effective vaccines/antivirals are yet available to treat Norovirus
      infection. Since the activity of RNA-dependent RNA polymerase (RdRp) plays a key
      role in genome replication and in the synthesis/amplification of subgenomic RNA,
      the enzyme is considered a promising target for antiviral drug development. In
      this context, following the identification of suramin and NF023 as Norovirus RdRp
      inhibitors, we analyzed the potential inhibitory role of naphthalene di-sulfonate
      (NAF2), a fragment derived from these two molecules. Although NAF2, tested in
      enzymatic polymerase inhibition assays, displayed low activity against RdRp
      (IC50=14MUM), the crystal structure of human Norovirus RdRp revealed a thumb
      domain NAF2 binding site that differs from that characterized for NF023/suramin.
      To further map the new potential inhibitory site, we focused on the structurally
      related molecule pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'
      disulfonate) tetrasodium salt (PPNDS). PPNDS displayed below-micromolar
      inhibitory activity versus human Norovirus RdRp (IC50=0.45MUM), similarly to
      suramin and NF023. Inspection of the crystal structure of the RdRp/PPNDS complex
      showed that the inhibitor bound to the NAF2 thumb domain site, highlighting the
      relevance of such new binding site for exploiting Norovirus RdRp inhibitors. 

PMID- 24316033
TI  - Specific bioelectrical impedance vector reference values for assessing body
      composition in the Italian elderly.
AB  - OBJECTIVE: To obtain specific bioelectrical impedance vector reference values for
      the healthy elderly Italian population, and to study age- and sex-related
      differences in body composition. DESIGN: The study group consisted of 560 healthy
      individuals (265 men and 295 women) aged 65 to 100 y, whose anthropometric
      (height, weight, and calf, arm and waist circumferences) and bioelectrical
      measurements (resistance [R] and reactance [Xc], at 50 kHz and 800 MUA) were
      recorded. R (Omega) and Xc (Omega) values were standardized for stature (H, m) to
      obtain the classic bioelectrical values. Specific values (resistivity [Rsp] and
      reactivity [Xcsp], Omega.cm) were obtained by multiplying R and Xc by a
      correction factor (A/L) that includes an estimate of the cross-sectional area of
      the body (A=0.45 arm area+0.10 waist area+0.45 calf area), where L=1.1H. RESULTS:
      Descriptive statistics were: Rsp (391.8+/-57.9), Xcsp (42.6+/-9.9), Zsp (394.2+/
      58.2), phase angle (6.2 degrees +/-1.2) in men; Rsp (462.0+/-80.1), Xcsp (47.9+/
      11.2), Zsp (464.6+/-80.5), phase angle (5.9 degrees +/-1.0) in women. The Xcsp
      and phase angle values showed a significant age-related decrease in both sexes,
      but especially in men, possibly relating to a gradual loss of muscle mass.
      Women's Rsp and Zsp values tended to drop, attributable to their declining
      proportion of fat mass. A declining sexual dimorphism was also apparent.
      CONCLUSIONS: Specific tolerance ellipses can be used for reference purposes for
      the Italian population when assessing body composition in gerontological practice
      and for epidemiological purposes.

PMID- 24316034
TI  - Panax ginseng is neuroprotective in a novel progressive model of Parkinson's
      disease.
AB  - Panax ginseng has been used in traditional Chinese medicine for centuries. Among
      its various benefits is a pluripotent targeting of the various events involved in
      neuronal cell death. This includes anti-inflammatory, anti-oxidant, and anti
      apoptotic effects. Indeed, ginseng extract and its individual ginsenosides have
      been demonstrated to influence a number of biochemical markers implicated in
      Parkinson's disease (PD) pathogenesis. We have reported previously that
      administration of the ginseng extract, G115, afforded robust neuroprotection in
      two rodent models of PD. However, these traditional rodent models are acute in
      nature and do accurately recapitulate the progressive nature of the disease.
      Chronic exposure to the dietary phytosterol glucoside, beta-sitosterol beta-d
      glucoside (BSSG) triggers the progressive development of neurological deficits,
      with behavioral and cellular features that closely approximate those observed in
      PD patients. Clinical signs and histopathology continue to develop for several
      months following cessation of exposure to the neurotoxic insult. Here, we
      utilized this model to further characterize the neuroprotective effects of the
      ginseng extract, G115. Oral administration of this extract significantly reduced
      dopaminergic cell loss, microgliosis, and accumulation of alpha-synuclein
      aggregates. Further, G115 administration fully prevented the development of
      locomotor deficits, in the form of reduced locomotor activity and coordination.
      These results suggest that ginseng extract may be a potential neuroprotective
      therapy for the treatment of PD. 

PMID- 24316035
TI  - Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in
      aged rats.
AB  - Aging exacerbates muscle loss and slows the recovery of muscle mass and function
      after disuse. In this study we investigated the potential that epigallocatechin-3
      gallate (EGCg), an abundant catechin in green tea, would reduce signaling for
      apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and
      the slow soleus muscle after hindlimb suspension (HLS) in senescent animals.
      Fischer 344 * Brown Norway inbred rats (age 34 months) received either EGCg (50
      mg/kg body weight), or water daily by gavage. One group of animals received HLS
      for 14 days and a second group of rats received 14 days of HLS, then the HLS was
      removed and they recovered from this forced disuse for 2 weeks. Animals that
      received EGCg over the HLS followed by 14 days of recovery, had a 14% greater
      plantaris muscle weight (p<0.05) as compared to the animals treated with the
      vehicle over this same period. Plantaris fiber area was greater after recovery in
      EGCg (2715.2+/-113.8 MUm(2)) vs. vehicle treated animals (1953.0+/-41.9 MUm(2)).
      In addition, activation of myogenic progenitor cells was improved with EGCg over
      vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle
      treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of
      pro-apoptotic proteins Bax (-22%), and FADD (-77%) was lower in EGCg treated
      plantaris muscles after recovery. While EGCg did not prevent unloading-induced
      atrophy, it improved muscle recovery after the atrophic stimulus in fast
      plantaris muscles. However, this effect was muscle specific because EGCg had no
      major impact in reversing HLS-induced atrophy in the slow soleus muscle of old
      rats.

PMID- 24316037
TI  - The long-term effects of a life-prolonging heat treatment on the Drosophila
      melanogaster transcriptome suggest that heat shock proteins extend lifespan.
AB  - Heat-induced hormesis, i.e. the beneficial effect of mild heat-induced stress,
      increases the average lifespan of many organisms. This effect, which depends on
      the heat shock factor, decreases the log mortality rate weeks after the stress
      has ceased. To identify candidate genes that mediate this lifespan-prolonging
      effect late in life, we treated flies with mild heat stress (34  degrees C for 2
      h) 3 times early in life and compared the transcriptomic response in these flies
      versus non-heat-treated controls 10-51 days after the last heat treatment. We
      found significant transcriptomic changes in the heat-treated flies. Several hsp70
      probe sets were up-regulated 1.7-2-fold in the mildly stressed flies weeks after
      the last heat treatment (P<0.01). This result was unexpected as the major
      Drosophila heat shock protein, Hsp70, is reported to return to normal levels of
      expression shortly after heat stress. We conclude that the heat shock response,
      and Hsp70 in particular, may be central to the heat-induced increase in the
      average lifespan in flies that are exposed to mild heat stress early in life.

PMID- 24316038
TI  - The value of neutrophil and lymphocyte count in frail older women.
AB  - Increasing evidence suggests that systemic inflammation is associated with many
      pathophysiological processes including frailty in older adults. We evaluated the
      relationships between white blood cell subtypes, geriatric assessment, and
      frailty syndrome and in particular, how they correlate with individual frailty
      criteria (involuntary loss of weight, low energy or exhaustion, slow mobility,
      muscle weakness, and low physical activity) in frail older women. There was a
      significant and positive correlation between the frailty score and neutrophil
      count, but a significantly negative correlation was found when this score was
      compared to the lymphocyte count. These associations were significant only for
      two frailty criteria: poor muscular strength and low physical activity. Further
      investigation into the role of white blood cell subtypes in ageing and its
      associated adverse outcomes in older adults is warranted, in particular in the
      loss of muscular strength and for poor physical activity. 

PMID- 24316036
TI  - Dysfunctional survival-signaling and stress-intolerance in aged murine and human
      myocardium.
AB  - Changes in cytoprotective signaling may influence cardiac aging, and underpin
      sensitization to ischemic insult and desensitization to 'anti-ischemic'
      therapies. We tested whether age-dependent shifts in ischemia-reperfusion (I-R)
      tolerance in murine and human myocardium are associated with reduced efficacies
      and coupling of membrane, cytoplasmic and mitochondrial survival-signaling.
      Hormesis (exemplified in ischemic preconditioning; IPC) and expression of
      proteins influencing signaling/stress-resistance were also assessed in mice.
      Mouse hearts (18 vs. 2-4 mo) and human atrial tissue (75+/-2 vs. 55+/-2 yrs)
      exhibited profound age-dependent reductions in I-R tolerance. In mice aging
      negated cardioprotection via IPC, G-protein coupled receptor (GPCR) agonism
      (opioid, A1 and A3 adenosine receptors) and distal protein kinase c (PKC)
      activation (4 nM phorbol 12-myristate 13-acetate; PMA). In contrast, p38-mitogen
      activated protein kinase (p38-MAPK) activation (1 MUM anisomycin), mitochondrial
      ATP-sensitive K(+) channel (mKATP) opening (50 MUM diazoxide) and permeability
      transition pore (mPTP) inhibition (0.2 MUM cyclosporin A) retained protective
      efficacies in older hearts (though failed to eliminate I-R tolerance
      differences). A similar pattern of change in protective efficacies was observed
      in human tissue. Murine hearts exhibited molecular changes consistent with
      altered membrane control (reduced caveolin-3, cholesterol and caveolae), kinase
      signaling (reduced p70 ribosomal s6 kinase; p70s6K) and stress-resistance
      (increased G-protein receptor kinase 2, GRK2; glycogen synthase kinase 3beta,
      GSK3beta; and cytosolic cytochrome c). In summary, myocardial I-R tolerance
      declines with age in association with dysfunctional hormesis and transduction of
      survival signals from GPCRs/PKC to mitochondrial effectors. Differential changes
      in proteins governing caveolar and mitochondrial function may contribute to
      signal dysfunction and stress-intolerance.

PMID- 24316040
TI  - Weakness, SR function and stress in gastrocnemius muscles of aged male rats.
AB  - Aging is associated with a decline in muscle force that exceeds loss of muscle
      mass, suggesting that factors other than sarcopenia affect age-related muscle
      weakness. Here, we investigate in situ muscle force and sarcoplasmic reticulum
      (SR) properties in gastrocnemius muscles of adult (6-8 months) and aged (24
      months) rats. Despite minimal loss of muscle mass, peak tetanic force was
      significantly reduced (-28%) in aged muscles. Adjusting for differences in muscle
      cross-sectional area mitigated the age difference (-23%), but it remained
      significant. The SR calcium release function was also impaired (-17%) with aging,
      although calcium uptake was not, and SR-associated glycogen increased (+30%) with
      aging. Western blotting revealed age related increases in Grp78,
      serinepalmitoyltransferase and neutral sphingomyelinase, suggesting that age
      increased the stress response and ceramide metabolism in the SR. In contrast
      Parkin, a protein associated with autophagic signaling, was reduced in the aged
      SR. These findings are consistent with a hypothesis that age-related impairments
      of the SR, possibly due to impaired autophagy and/or altered membrane metabolism,
      contribute to age-related muscle weakness, independent of changes in muscle mass.

PMID- 24316039
TI  - Lifespan extension by cranberry supplementation partially requires SOD2 and is
      life stage independent.
AB  - Many nutraceuticals and pharmaceuticals have been shown to promote healthspan and
      lifespan. However, the mechanisms underlying the beneficial effects of
      prolongevity interventions and the time points at which interventions should be
      implemented to achieve beneficial effects are not well characterized. We have
      previously shown that a cranberry-containing nutraceutical can promote lifespan
      in worms and flies and delay age-related functional decline of pancreatic cells
      in rats. Here we investigated the mechanism underlying lifespan extension induced
      by cranberry and the effects of short-term or life stage-specific interventions
      with cranberry on lifespan in Drosophila. We found that lifespan extension
      induced by cranberry was associated with reduced phosphorylation of ERK, a
      component of oxidative stress response MAPK signaling, and slightly increased
      phosphorylation of AKT, a component of insulin-like signaling. Lifespan extension
      was also associated with a reduced level of 4-hydroxynonenal protein adducts, a
      biomarker of lipid oxidation. Moreover, lifespan extension induced by cranberry
      was partially suppressed by knockdown of SOD2, a major mitochondrial superoxide
      scavenger. Furthermore, cranberry supplementation was administered in three life
      stages of adult flies, health span (3-30 days), transition span (31-60 days) and
      senescence span (61 days to the end when all flies died). Cranberry
      supplementation during any of these life stages extended the remaining lifespan
      relative to the non-supplemented and life stage-matched controls. These findings
      suggest that cranberry supplementation is sufficient to promote longevity when
      implemented during any life stage, likely through reducing oxidative damage.

PMID- 24316042
TI  - Zebrafish (Danio rerio) as a model for the study of aging and exercise: physical
      ability and trainability decrease with age.
AB  - A rapidly aging global population has motivated the development and use of models
      for human aging. Studies on aging have shown parallels between zebrafish and
      humans at the internal organization level; however, few parallels have been
      studied at the whole-organism level. Furthermore, the effectiveness of exercise
      as a method to mitigate the effects of aging has not been studied in zebrafish.
      We investigated the effects of aging and intermittent exercise on swimming
      performance, kinematics and behavior. Young, middle-aged and old zebrafish (20
      29, 36-48 and 60-71% of average lifespan, respectively) were exercised to
      exhaustion in endurance and sprint swimming tests once a week for four weeks.
      Both endurance and sprint performance decreased with increased age. Swimming
      performance improved with exercise training in young and middle-aged zebrafish,
      but not in old zebrafish. Tail-beat amplitude, which is akin to stride length in
      humans, increased for all age groups with training. Zebrafish turning frequency,
      which is an indicator of routine activity, decreased with age but showed no
      change with exercise. In sum, our results show that zebrafish exhibit a decline
      in whole-organism performance and trainability with age. These findings closely
      resemble the senescence-related declines in physical ability experienced by
      humans and mammalian aging models and therefore support the use of zebrafish as a
      model for human exercise and aging. 

PMID- 24316041
TI  - Advanced oxidation protein products accelerate bone deterioration in aged rats.
AB  - Advanced oxidation protein products (AOPPs) are novel markers of oxidation
      mediated protein damage, and accumulation of AOPPs is involved in many
      pathophysiological conditions. Our previous studies demonstrated that the serum
      level of AOPPs negatively correlated with the age-related change in bone mineral
      density (BMD) in rats and that AOPPs inhibited rat osteoblast-like cell
      proliferation and differentiation in vitro. However, whether AOPPs are involved
      in senile osteoporosis is still largely unknown. The present study aimed to test
      the hypothesis that accumulation of AOPPs might accelerate bone deterioration in
      aged rats. Seventy 18-month-old male Sprague Dawley (SD) rats were randomized to
      intravenous injection of vehicle, native rat serum albumin (RSA), AOPPs-modified
      RSA (AOPPs-RSA) with or without oral administration of apocynin (a nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase inhibitor), or apocynin alone.
      After treatment for 8 weeks or 16 weeks, seven rats in each group were
      sacrificed. Bone and blood samples were harvested for BMD measurement, micro
      computed tomographic (micro-CT) imaging, and biochemical analysis of circulating
      bone biomarkers. Compared to RSA- or vehicle-treated rats, AOPPs-RSA-treated
      animals displayed significantly decreased total vertebral BMD and deteriorated
      microstructure in both the tibias and the lumbar vertebral bodies, which were
      associated with down-regulated plasma bone-specific alkaline phosphatase
      concentration and up-regulated tartrate-resistant acid phosphatase 5b
      concentration. These AOPPs-induced perturbations in aged rats could be prevented
      by the oral administration of apocynin. However, no significant differences in
      BMD were detected in the femurs or the biomechanical parameters tested between
      the different treatment groups. These data suggest that accumulation of AOPPs
      accelerates bone deterioration in aged rats, likely via the activation of NADPH
      oxidase. This study provides new information toward understanding the pathogenic
      basis of senile osteoporosis and may provide targets for intervention.

PMID- 24316043
TI  - Meta-analysis of MTHFR C677T and A1298C gene polymorphisms: association with the
      risk of hepatocellular carcinoma.
AB  - OBJECTIVE: Several studies have indicated an association between
      methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and the risk of
      hepatocellular carcinoma (HCC). However, the conclusions are inconsistent.
      Therefore, a meta-analysis was performed. METHODS: Databases like Pubmed, EMBASE,
      and EBSCO (up to September 2012) were searched to retrieve case-control trials
      about MTHFR (C677T or A1298C) polymorphisms and HCC. Literatures were
      independently screened by two researchers according to the inclusion and
      exclusion criteria. Data were extracted and analyzed by software STATA 11.0.
      RESULTS: Nine studies were included with 10 datasets and 5132 cases. C677T
      polymorphism was associated with HCC risk in a heterozygous model (TT vs. CT:
      OR=1.20, 95% CI: 1.02-1.40). For the A1298C polymorphism, a significantly
      decreased HCC risk was found in the dominant, heterozygous and homozygous models
      (CC vs. AA+AC: OR=0.52, 95% CI: 0.33-0.80; CC vs. AC: OR=0.50, 95% CI: 0.32-0.79;
      CC vs. AA: OR=0.52, 95% CI: 0.33-0.81). Subgroup analysis stratified by ethnicity
      and type of control further indicated decreased HCC risks in Asians (CC vs.
      AA+AC: OR=0.47, 95% CI: 0.26-0.84; CC vs. AC: OR=0.41, 95% CI: 0.24-0.71; CC vs.
      AA: OR=0.46, 95% CI: 0.27-0.78), studies with controls of healthy people (CC vs.
      AA: OR=0.54, 95% CI: 0.31-0.93; CC vs. AC: OR=0.54, 95% CI: 0.31-0.94; CC vs.
      AA+AC: OR=0.55, 95% CI: 0.32-0.94), and controls of non-HCC patients (CC vs. AC:
      OR=0.43, 95% CI: 0.19-0.96). CONCLUSIONS: Homozygous carriers of MTHFR C677T
      mutation are more susceptible to HCC, but homozygous mutations of MTHFR A1298C
      may play a protective role for developing HCC.

PMID- 24316044
TI  - Accurate prediction of protein structural classes by incorporating predicted
      secondary structure information into the general form of Chou's pseudo amino acid
      composition.
AB  - Extracting good representation from protein sequence is fundamental for protein
      structural classes prediction tasks. In this paper, we propose a novel and
      powerful method to predict protein structural classes based on the predicted
      secondary structure information. At the feature extraction stage, a 13
      dimensional feature vector is extracted to characterize general contents and
      spatial arrangements of the secondary structural elements of a given protein
      sequence. Specially, four segment-level features are designed to elevate
      discriminative ability for proteins from the alpha/beta and alpha+beta classes.
      After the features are extracted, a multi-class non-linear support vector machine
      classifier is used to implement protein structural classes prediction. We report
      extensive experiments comparing the proposed method to the state-of-the-art in
      protein structural classes prediction on three widely used low-similarity
      benchmark datasets: FC699, 1189 and 640. Our method achieves competitive
      performance on prediction accuracies, especially for the overall prediction
      accuracies which have exceeded the best reported results on all of the three
      datasets. 

PMID- 24316045
TI  - Aggregated chromosomes transfer in human oocytes.
AB  - Germinal-vesicle (GV) transfer, spindle-chromosome complex transfer in metaphase
      II oocytes and two pronuclei transfer have been evaluated as possible treatments
      for patients who have mitochondrial diseases. However, GV transfers often lead to
      heteroplasmy while the other two methods are frequently associated with
      aneuploidy. The present study used a new method based on the transfer of
      aggregated chromosomes, which occurs in human oocytes, before the metaphase
      spindle is established. 

PMID- 24316046
TI  - Photophysical properties and in vitro and in vivo photoinduced antitumor activity
      of cationic salts of meso-tetrakis(N-alkyl-3-pyridyl)bacteriochlorins.
AB  - Physico-chemical properties, biodistribution in animal tissues, and PDT efficacy
      of bacteriochlorin photosensitizers, namely cationic salts of synthetic meso
      tetrakis(N-alkyl-3-pyridyl)bacteriochlorins were studied in NEr2 cell line and in
      the LLC mouse model. The tested compounds showed high stability in the dark and
      high in vitro phototoxicity against NEr2 cells (the half maximal inhibitory
      concentration LD50 in the range from 0.34+/-0.03 to 1.5+/-0.03MUm). Synthetic
      bacteriochlorins rapidly accumulate in mouse tumor tissue with tumor-to-normal
      tissue fluorescence contrast ratios of 2.3-3.3, possess high PDT activity against
      LLC cells: inhibition of tumor growth, TGI 85.8-100%, increase in life span, ILS
      105.7-129.2%, response rate, RR 50-100%. The highest PDT efficacy was found for
      meso-tetrakis[1-(4'-bromobutyl)-3-pyridyl]bacteriochlorin tetrabromide (IC50
      0.34+/-0.03MUm in vitro, TGI and RR 100% in vivo). 

PMID- 24316047
TI  - Innate immunity to dengue virus infection and subversion of antiviral responses.
AB  - Dengue is a major public health issue in tropical and subtropical regions
      worldwide. The four serotypes of dengue virus (DENV1-DENV4) are spread primarily
      by Aedes aegypti and Aedes albopictus mosquitoes, whose geographic range
      continues to expand. Humans are the only host for epidemic strains of DENV, and
      the virus has developed sophisticated mechanisms to evade human innate immune
      responses. The host cell's first line of defense begins with an intracellular
      signaling cascade resulting in production of interferon alpha/beta (IFN
      alpha/beta), which promotes intracellular antiviral responses and helps initiates
      the adaptive response during the course of DENV infection. In response, DENV has
      developed numerous ways to subvert these intracellular antiviral responses and
      directly inhibit cellular signaling cascades. Specifically, DENV manipulates the
      unfolded protein response and autophagy to counter cellular stress and delay
      apoptosis. The DENV non-structural protein NS4B and subgenomic flavivirus RNA
      interfere with the RNA interference pathway by inhibiting the RNase Dicer. During
      heterotypic secondary DENV infection, subneutralizing antibodies can enable viral
      uptake through Fcgamma receptors and down-regulate signaling cascades initiated
      via the pattern recognition receptors TLR-3 and MDA5/RIG-I, thus reducing the
      antiviral state of the cell. The DENV NS2B/3 protein cleaves human STING/MITA,
      interfering with induction of IFN-alpha/beta. Finally, DENV NS2A, NS4A, and NS4B
      complex together to block STAT1 phosphorylation, while NS5 binds and promotes
      degradation of human STAT2, thus preventing formation of the STAT1/STAT2
      heterodimer and its transcriptional induction of interferon stimulating genes.
      Here, we discuss the host innate immune response to DENV and the mechanisms of
      immune evasion that DENV has developed to manipulate cellular antiviral
      responses. 

PMID- 24316050
TI  - Acetylsalicylic acid therapy: influence of metformin use and other variables on
      urinary 11-dehydrothromboxane B2 levels.
AB  - BACKGROUND: The effect of acetylsalicylic acid (ASA) may be measured through the
      analysis of urinary concentrations of 11-dehydrothromboxane B2 (11-dhTXB2), a
      metabolite of thromboxane A2, which is a potent platelet aggregant agent. It has
      been suggested that metformin (an oral antidiabetic drug) could improve oxidative
      stress and control platelet activation in type 2 diabetic patients, potentially
      reducing cardiovascular risk. We determined the concentrations of urinary 11
      dhTXB2 in type 2 diabetic patients taking ASA and its concentrations with
      metformin use and several other clinical variables (hypertension, age, gender,
      smoking, body mass index, insulin and statin use), considering a reduction of at
      least 75% in the concentrations of this marker as a target, compared to results
      before ASA intake. METHODS: Urinary concentrations of 11-dhTXB2 of 81 type 2
      diabetic patients were measured before and at 15 days taking 100 mg of aspirin
      daily. RESULTS: Most patients who presented a reduction of 11-dhTXB2 above 75%
      were under metformin use. This reduction was achieved in 51.5% of patients taking
      this drug, against 20.0% in the patients who were not (p=0.027). The analysis of
      the other variables did not show a significant difference. The use of metformin
      appears to play a role in the reduction of 11-dhTXB2 concentrations in type 2
      diabetic patients. CONCLUSION: According to previous reports, hyperglycemia
      control seems to be a determinant factor for the success of ASA therapy, given
      the influence of metformin in the reduction of 11-dhTXB2 concentrations.

PMID- 24316049
TI  - Structural studies of Streptococcus pyogenes streptolysin O provide insights into
      the early steps of membrane penetration.
AB  - Cholesterol-dependent cytolysins (CDCs) are a large family of bacterial toxins
      that exhibit a dependence on the presence of membrane cholesterol in forming
      large pores in cell membranes. Significant changes in the three-dimensional
      structure of these toxins are necessary to convert the soluble monomeric protein
      into a membrane pore. We have determined the crystal structure of the
      archetypical member of the CDC family, streptolysin O (SLO), a virulence factor
      from Streptococcus pyogenes. The overall fold is similar to previously reported
      CDC structures, although the C-terminal domain is in a different orientation with
      respect to the rest of the molecule. Surprisingly, a signature stretch of CDC
      sequence called the undecapeptide motif, a key region involved in membrane
      recognition, adopts a very different structure in SLO to that of the well
      characterized CDC perfringolysin O (PFO), although the sequences in this region
      are identical. An analysis reveals that, in PFO, there are complementary
      interactions between the motif and the rest of domain 4 that are lost in SLO.
      Molecular dynamics simulations suggest that the loss of a salt bridge in SLO and
      a cation-pi interaction are determining factors in the extended conformation of
      the motif, which in turn appears to result in a greater flexibility of the
      neighboring L1 loop that houses a cholesterol-sensing motif. These differences
      may explain the differing abilities of SLO and PFO to efficiently penetrate
      target cell membranes in the first step of toxin insertion into the membrane. 

PMID- 24316051
TI  - Development and evaluation of RapTAT: a machine learning system for concept
      mapping of phrases from medical narratives.
AB  - Rapid, automated determination of the mapping of free text phrases to pre-defined
      concepts could assist in the annotation of clinical notes and increase the speed
      of natural language processing systems. The aim of this study was to design and
      evaluate a token-order-specific naive Bayes-based machine learning system
      (RapTAT) to predict associations between phrases and concepts. Performance was
      assessed using a reference standard generated from 2860 VA discharge summaries
      containing 567,520 phrases that had been mapped to 12,056 distinct Systematized
      Nomenclature of Medicine - Clinical Terms (SNOMED CT) concepts by the MCVS
      natural language processing system. It was also assessed on the manually
      annotated, 2010 i2b2 challenge data. Performance was established with regard to
      precision, recall, and F-measure for each of the concepts within the VA documents
      using bootstrapping. Within that corpus, concepts identified by MCVS were broadly
      distributed throughout SNOMED CT, and the token-order-specific language model
      achieved better performance based on precision, recall, and F-measure (0.95+/
      0.15, 0.96+/-0.16, and 0.95+/-0.16, respectively; mean+/-SD) than the bag-of
      words based, naive Bayes model (0.64+/-0.45, 0.61+/-0.46, and 0.60+/-0.45,
      respectively) that has previously been used for concept mapping. Precision,
      recall, and F-measure on the i2b2 test set were 92.9%, 85.9%, and 89.2%
      respectively, using the token-order-specific model. RapTAT required just 7.2ms to
      map all phrases within a single discharge summary, and mapping rate did not
      decrease as the number of processed documents increased. The high performance
      attained by the tool in terms of both accuracy and speed was encouraging, and the
      mapping rate should be sufficient to support near-real-time, interactive
      annotation of medical narratives. These results demonstrate the feasibility of
      rapidly and accurately mapping phrases to a wide range of medical concepts based
      on a token-order-specific naive Bayes model and machine learning. 

PMID- 24316048
TI  - Toll-like receptors in antiviral innate immunity.
AB  - Toll-like receptors (TLRs) are fundamental sensor molecules of the host innate
      immune system, which detect conserved molecular signatures of a wide range of
      microbial pathogens and initiate innate immune responses via distinct signaling
      pathways. Various TLRs are implicated in the early interplay of host cells with
      invading viruses, which regulates viral replication and/or host responses,
      ultimately impacting on viral pathogenesis. To survive the host innate defense
      mechanisms, many viruses have developed strategies to evade or counteract
      signaling through the TLR pathways, creating an advantageous environment for
      their propagation. Here we review the current knowledge of the roles TLRs play in
      antiviral innate immune responses, discuss examples of TLR-mediated viral
      recognition, and describe strategies used by viruses to antagonize the host
      antiviral innate immune responses. 

PMID- 24316052
TI  - Federated Aggregate Cohort Estimator (FACE): an easy to deploy, vendor neutral,
      multi-institutional cohort query architecture.
AB  - Cross-institutional data sharing for cohort discovery is critical to enabling
      future research. While particularly useful in rare diseases, the ability to
      target enrollment and to determine if an institution has a sufficient number of
      patients is valuable in all research, particularly in the initiation of projects
      and collaborations. An optimal technology solution would work with any source
      database with minimal resource investment for deployment and would meet all
      necessary security and confidentiality requirements of participating
      organizations. We describe a platform-neutral reference implementation to meet
      these requirements: the Federated Aggregate Cohort Estimator (FACE). FACE was
      developed and implemented through a collaboration of The University of Alabama at
      Birmingham (UAB), The Ohio State University (OSU), the University of
      Massachusetts Medical School (UMMS), and the Denver Health and Hospital Authority
      (DHHA) a clinical affiliate of the Colorado Clinical and Translational Sciences
      Institute. The reference implementation of FACE federated diverse SQL data
      sources and an i2b2 instance to estimate combined research subject availability
      from three institutions. It used easily-deployed virtual machines and addressed
      privacy and security concerns for data sharing. 

PMID- 24316053
TI  - Impact of family planning health talks by lay health workers on contraceptive
      knowledge and attitudes among HIV-infected patients in rural Kenya.
AB  - OBJECTIVE: To determine if a health talk on family planning (FP) by community
      clinic health assistants (CCHAs) will improve knowledge, attitudes and behavioral
      intentions about contraception in HIV-infected individuals. METHODS: A 15-min FP
      health talk was given by CCHAs in six rural HIV clinics to a sample of 49 HIV
      infected men and women. Effects of the health talk were assessed through a
      questionnaire administered before the health talk and after completion of the
      participant's clinic visit. RESULTS: Following the health talk, there was a
      significant increase in knowledge about contraceptives (p<.0001), side-effects
      (p<.0001), and method-specific knowledge about IUCDs (p<.001), implants
      (p<.0001), and injectables (p<.05). Out of 31 women and 18 men enrolled, 14 (45%)
      women and 6 (33%) men intended to try a new contraceptive. Participant attitudes
      toward FP were high before and after the health talk (median 4 of 4). CONCLUSION:
      A health talk delivered by CCHAs can increase knowledge of contraception and
      promote the intention to try new more effective contraception among HIV-infected
      individuals. PRACTICE IMPLICATIONS: FP health talks administered by lay-health
      providers to HIV-infected individuals as they wait for HIV services can influence
      FP knowledge and intention to use FP.

PMID- 24316054
TI  - Between two worlds.
AB  - OBJECTIVE: To reflect on the challenges of caring for an elderly ill parent who
      lives afar and to pronounce the importance of system-wide standards in nursing
      homes and elderly care. METHOD: Personal memoire in which the author conjures up
      powerful images of contrasting healthcare systems and the tension of living in
      two countries. RESULTS: The author discusses many aspects of healthcare for the
      elderly. Some of the pictures depicted include the picture of a gradually
      declining memory of an Alzheimer's disease patient and the challenges of elderly
      care. CONCLUSION: There is a value of medical knowledge, an importance of nursing
      homes designs and regulation, and a significance of simple concepts such as a "do
      not-resuscitate" order. PRACTICE IMPLICATIONS: Care for the elderly can be
      exhausting physically and emotionally; system-wide changes and standards are
      important in minimizing its impact.

PMID- 24316055
TI  - Does the use of shared decision-making consultation behaviors increase treatment
      decision-making satisfaction among Chinese women facing decision for breast
      cancer surgery?
AB  - OBJECTIVE: To assess the extent to which breast surgical consultations used
      shared decision making (SDM), identify factors associated with use of SDM, and
      assess if using SDM increases decision-making satisfaction. METHODS: Two hundred
      and eighty-three video-recorded diagnostic-treatment decision consultations
      between breast surgeons and women with breast cancer were assessed using the
      Decision Analysis System for Oncology (DAS-O) coding system designed for
      assessing SDM behaviors. Women completed a questionnaire at pre-consultation, one
      week post-consultation and one-month post-surgery. Patient outcomes included
      decision conflict, patient satisfaction with medical consultation, and decision
      regret. RESULTS: Overall, the level of SDM behaviors was low. The extent of SDM
      behavior within consultation was related to greater consultation duration
      (p<0.001), more than one treatment being offered (p<0.001), and fewer questions
      raised by patients/companions (p<0.05). While use of SDM consultation did not
      influence post-consultation decision conflict, it increased satisfaction with
      information given and explained, patients' feelings of trust and confidence in
      their surgeons, and reduced post-surgical decision regret. CONCLUSION: These
      breast surgical consultations mostly adopted informed treatment decision-making
      approaches. Using SDM improved patient consultation and decision satisfaction.
      PRACTICE IMPLICATIONS: The study findings highlight a need to reinforce the
      importance of SDM in consultations among breast surgeons.

PMID- 24316057
TI  - MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond.
AB  - One mechanism by which communication between the endoplasmic reticulum (ER) and
      mitochondria is achieved is by close juxtaposition between these organelles via
      mitochondria-associated membranes (MAM). The MAM consist of a region of the ER
      that is enriched in several lipid biosynthetic enzyme activities and becomes
      reversibly tethered to mitochondria. Specific proteins are localized, sometimes
      transiently, in the MAM. Several of these proteins have been implicated in
      tethering the MAM to mitochondria. In mammalian cells, formation of these contact
      sites between MAM and mitochondria appears to be required for key cellular events
      including the transport of calcium from the ER to mitochondria, the import of
      phosphatidylserine into mitochondria from the ER for decarboxylation to
      phosphatidylethanolamine, the formation of autophagosomes, regulation of the
      morphology, dynamics and functions of mitochondria, and cell survival. This
      review focuses on the functions proposed for MAM in mediating these events in
      mammalian cells. In light of the apparent involvement of MAM in multiple
      fundamental cellular processes, recent studies indicate that impaired contact
      between MAM and mitochondria might underlie the pathology of several human
      neurodegenerative diseases, including Alzheimer's disease. Moreover, MAM has been
      implicated in modulating glucose homeostasis and insulin resistance, as well as
      in some viral infections. 

PMID- 24316056
TI  - Distinct communication patterns during genetic counseling for late-onset
      Alzheimer's risk assessment.
AB  - OBJECTIVE: To identify and characterize patient-provider communication patterns
      during disclosure of Alzheimer's disease genetic susceptibility test results and
      to assess whether these patterns reflect differing models of genetic counseling.
      METHODS: 262 genetic counseling session audio-recordings were coded using the
      Roter Interactional Analysis System. Cluster analysis was used to distinguish
      communication patterns. Bivariate analyses were used to identify characteristics
      associated with the patterns. RESULTS: Three patterns were identified: Biomedical
      Provider-Teaching (40%), Biomedical-Patient-Driven (34.4%), and Psychosocial
      Patient-Centered (26%). Psychosocial-Patient-Centered and Biomedical-Provider
      Teaching sessions included more female participants while the Biomedical-Patient
      Driven sessions included more male participants (p=0.04). CONCLUSION:
      Communication patterns observed reflected the teaching model primarily, with
      genetic counseling models less frequently used. The emphasis on biomedical
      communication may potentially be at the expense of more patient-centered
      approaches. PRACTICE IMPLICATIONS: To deliver more patient-centered care,
      providers may need to better balance the ratio of verbal exchange with their
      patients, as well as their educational and psychosocial discussions. The
      delineation of these patterns provides insights into the genetic counseling
      process that can be used to improve the delivery of genetic counseling care.
      These results can also be used in future research designed to study the
      association between patient-centered genetic counseling communication and
      improved patient outcomes.

PMID- 24316058
TI  - A complex rhythm treated simply: fascicular ventricular tachycardia.

PMID- 24316060
TI  - The role of miR-146a in dorsal root ganglia neurons of experimental diabetic
      peripheral neuropathy.
AB  - Sensory neurons mediate diabetic peripheral neuropathy. Using a mouse model of
      diabetic peripheral neuropathy (BKS.Cg-m+/+Lepr(db)/J (db/db) mice) and cultured
      dorsal root ganglion (DRG) neurons, the present study showed that hyperglycemia
      downregulated miR-146a expression and elevated interleukin-1 receptor-activated
      kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6)
      levels in DRG neurons. In vitro, elevation of miR-146a by miR-146a mimics in DRG
      neurons increased neuronal survival under high-glucose conditions. Downregulation
      and elevation of miR-146a in DRG neurons, respectively, were inversely related to
      IRAK1 and TRAF6 levels. Treatment of diabetic peripheral neuropathy with
      sildenafil, a phosphodiesterase type 5 inhibitor, augmented miR-146a expression
      and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of
      miR-146a in DRG neurons abolished the effect of sildenafil on DRG neuron
      protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia.
      Our data provide the first evidence showing that miR-146a plays an important role
      in mediating DRG neuron apoptosis under hyperglycemic conditions. 

PMID- 24316062
TI  - Tumour co-expression of apelin and its receptor is the basis of an autocrine loop
      involved in the growth of colon adenocarcinomas.
AB  - Using a cancer profiling array, our laboratory has shown that apelin gene is up
      regulated in half of colon adenocarcinomas. We have therefore postulated that
      apelin signalling might play a prominent role in the growth of colon tumours. We
      first confirmed by immunohistochemistry that apelin peptide is overexpressed in
      human colon adenomas and adenocarcinomas. We also observed a significant
      overexpression of apelin receptor (APJ) in adjacent sections. We then
      demonstrated that several colorectal cancer cell lines also expressed apelin and
      its receptor, the highest gene and peptide expression being detected in LoVo
      cells. In this cell line, the expression and functionality of apelin receptor
      were revealed by apelin-induced adenylyl cyclase inhibition and Akt
      phosphorylation. In addition, apelin clearly protected LoVo cells from apoptosis
      by inactivating a caspase-dependent pathway and decreasing the degradation of
      poly ADP ribose polymerase protein (PARP). Finally, treatment of these tumour
      cells by the (F13A)apelin13 receptor antagonist significantly reduced their
      proliferation rate. Altogether, these data suggest the existence of an autocrine
      loop by which constitutive activation of apelin signalling should participate in
      the growth of colon adenocarcinomas. Accordingly, apelin signalling is a
      promising pharmacological target for the treatment of human colon adenomas and
      adenocarcinomas. 

PMID- 24316059
TI  - Imaging small vessel-associated white matter changes in aging.
AB  - Alterations in cerebrovascular structure and function may underlie the most
      common age-associated cognitive, psychiatric, and neurological conditions
      presented by older adults. Although much remains to understand, existing research
      suggests several age-associated detrimental conditions may be mediated through
      sometimes subtle small vessel-induced damage to the cerebral white matter. Here
      we review a selected portion of the vast work that demonstrates links between
      changes in vascular and neural health as a function of advancing age, and how
      even changes in low-to-moderate risk individuals, potentially beginning early in
      the adult age-span, may have an important impact on functional status in late
      life. 

PMID- 24316061
TI  - Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor
      expression changes in spiral ganglion neurons of the mouse.
AB  - Age-related hearing loss - presbycusis - is the number one communication disorder
      and most prevalent neurodegenerative condition of our aged population. Although
      speech understanding in background noise is quite difficult for those with
      presbycusis, there are currently no biomedical treatments to prevent, delay or
      reverse this condition. A better understanding of the cochlear mechanisms
      underlying presbycusis will help lead to future treatments. Objectives of the
      present study were to investigate GABAA receptor subunit alpha1, nicotinic
      acetylcholine (nACh) receptor subunit beta2, and N-methyl-d-aspartate (NMDA)
      receptor subunit NR1 mRNA and protein expression changes in spiral ganglion
      neurons (SGN) of the CBA/CaJ mouse cochlea, that occur in age-related hearing
      loss, utilizing quantitative immunohistochemistry and semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) techniques. We found that
      auditory brainstem response (ABR) thresholds shifted over 40dB from 3 to 48kHz in
      old mice compared to young adults. DPOAE thresholds also shifted over 40dB from 6
      to 49kHz in old mice, and their amplitudes were significantly decreased or absent
      in the same frequency range. SGN density decreased with age in basal, middle and
      apical turns, and SGN density of the basal turn declined the most. A positive
      correlation was observed between SGN density and ABR wave 1amplitude. mRNA and
      protein expression of GABAAR alpha1 and AChR beta2 decreased with age in SGNs in
      the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with
      age in SGNs of the old mice. These findings demonstrate that there are
      functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in
      CBA mouse SGNs reflecting their degeneration, which may be related to functional
      changes in cochlear synaptic transmission with age, suggesting biological
      mechanisms for peripheral age-related hearing loss. 

PMID- 24316064
TI  - Fish biomarkers for regulatory identification of endocrine disrupting chemicals.
AB  - Demonstrating chemical-induced adverse effects, endocrine mechanisms/modes of
      action (MOAs) and their causal link is needed for regulatory identification of
      endocrine disrupting chemicals (EDCs). This paper addresses critical issues over
      MOAs and their causal link to changes in endpoints. Vitellogenin (VTG), secondary
      sex characteristics (SSC), and sex ratio (also an apical endpoint) are indicative
      of chemicals interfering with EAS (estrogen, androgen and steroidogenesis)
      pathways. These biomarkers, however, can be changed by non-EAS chemicals,
      systemic toxicity and the stress response. Examples are shown that proving causal
      link between MOAs and changes in endpoints may be difficult for regulatory
      identification of EDCs. The paper concludes that both in vitro and in vivo data
      are needed to define MOAs for regulatory identification of EDCs. Further
      development of guidance documents for data interpretation and for defining the
      level of evidence is needed for regulatory identification of EDCs. 

PMID- 24316063
TI  - Preoperative chemo-radiation therapy for localised retroperitoneal sarcoma: a
      phase I-II study from the Italian Sarcoma Group.
AB  - BACKGROUND: To study feasibility, safety and activity of the combination of high
      dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative
      treatment for resectable localised retroperitoneal sarcoma (RPS). METHODS:
      Patients received three cycles of HLI (14 g/m2). RT was started in combination
      with second cycle and administered up to a total dose of 50.4 Gy. Surgery was
      scheduled 4-6 weeks after the end of RT. Primary end-point was 3-year relapse
      free survival (RFS). The trial is registered with ITASARC_*II_2004_003. FINDINGS:
      Between December 2003 and 2010, 83 patients were recruited. Main histological
      subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated
      liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120
      mm (interquartile (IQ) range=82-160). The overall preoperative treatment was
      completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73.
      Four patients progressed before surgery and were not operated. 79 patients
      underwent surgery. At a median follow-up of 4.8 years (IQ range = 3-6.1), 23 and
      15 patients developed local recurrence (LR) and distant metastases (DM); 30
      patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90%
      confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74
      (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of
      LR and DM at 5 years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06).
      INTERPRETATION: The combination of preoperative HLI and RT was feasible in two
      thirds of patients, while preoperative RT could be completed in most (73/83).
      Although a systemic coverage can be added to RT when this is felt to be
      appropriate, the ongoing international phase III trial is exploring the role of
      RT alone. FUNDING: This is a pure academic trial. No funding sources contributed
      to it.

PMID- 24316065
TI  - Impact of elevated CO2 concentration on dynamics of leaf photosynthesis in Fagus
      sylvatica is modulated by sky conditions.
AB  - It has been suggested that atmospheric CO2 concentration and frequency of cloud
      cover will increase in future. It remains unclear, however, how elevated CO2
      influences photosynthesis under complex clear versus cloudy sky conditions.
      Accordingly, diurnal changes in photosynthetic responses among beech trees grown
      at ambient (AC) and doubled (EC) CO2 concentrations were studied under
      contrasting sky conditions. EC stimulated the daily sum of fixed CO2 and light
      use efficiency under clear sky. Meanwhile, both these parameters were reduced
      under cloudy sky as compared with AC treatment. Reduction in photosynthesis rate
      under cloudy sky was particularly associated with EC-stimulated, xanthophyll
      dependent thermal dissipation of absorbed light energy. Under clear sky, a
      pronounced afternoon depression of CO2 assimilation rate was found in sun-adapted
      leaves under EC compared with AC conditions. This was caused in particular by
      stomata closure mediated by vapour pressure deficit. 

PMID- 24316066
TI  - Reduced climate sensitivity of carbon, oxygen and hydrogen stable isotope ratios
      in tree-ring cellulose of silver fir (Abies alba Mill.) influenced by background
      SO2 in Franconia (Germany, Central Europe).
AB  - The climate sensitivity of carbon (delta(13)C), oxygen (delta(18)O) and hydrogen
      (delta(2)H) isotope signatures in tree-ring cellulose of Abies alba Mill. from a
      marginally industrialized area of Franconia (Germany) was analysed for the last
      130 years. All isotopes preserve climatic signals up to c. 1950 AD. After 1950 we
      observe a clear reduction in climate sensitivity of delta(13)C and delta(2)H
      while delta(18)O - climate relations remain well pronounced. Nevertheless
      statistical tests implied that SO2 background emissions of West Germany had
      influenced isotope signatures long before 1950. The relationships between isotope
      values and concentrations of SO2, dust, O3 and NO2 at the regional level during
      the period 1979-2006 indicate that delta(13)C and delta(18)O were influenced
      primarily by SO2. The impact of SO2 on delta(2)H was negligible, but the observed
      reduction of climate sensitivity may be caused by synergic influences. The
      results have significant implications if isotope signatures from tree-rings from
      anthropogenic influenced regions are used to reconstruct past climate. 

PMID- 24316067
TI  - Herbicide impact on non-target plant reproduction: what are the toxicological and
      ecological implications?
AB  - Declining plant diversity and abundance have been widely reported in agro
      ecosystems of North America and Europe. Intensive use of herbicides within
      cropfields and the associated drift in adjacent habitats are partly responsible
      for this change. The objectives of this work were to quantify the phenological
      stages of non-target plants in in-situ field situations during herbicide spray
      and to compare plant susceptibility at different phenological stages. Results
      demonstrated that a large number of non-target plants had reached reproductive
      stages during herbicide spray events in woodlots and hedgerows, both in Canada
      and Denmark where vegetation varies considerably. In addition, delays in
      flowering and reduced seed production occurred widely on plants sprayed at the
      seedling stage or at later reproductive periods, with plants sprayed at
      reproductive stages often exhibiting more sensitivity than those sprayed as
      seedlings. Ecological risk assessments need to include reproductive endpoints. 

PMID- 24316068
TI  - Utilizing thin-film solid-phase extraction to assess the effect of organic carbon
      amendments on the bioavailability of DDT and dieldrin to earthworms.
AB  - Improved approaches are needed to assess bioavailability of hydrophobic organic
      compounds in contaminated soils. Performance of thin-film solid-phase extraction
      (TF-SPE) using vials coated with ethylene vinyl acetate was compared to earthworm
      bioassay (Lumbricus terrestris). A DDT and dieldrin contaminated soil was amended
      with four organic carbon materials to assess the change in bioavailability.
      Addition of organic carbon significantly lowered bioavailability for all
      compounds except for 4,4'-DDT. Equilibrium concentrations of compounds in the
      polymer were correlated with uptake by earthworms after 48d exposure (R(2) =
      0.97; p < 0.001), indicating TF-SPE provided an accurate uptake simulation.
      Bioavailability of residues in soil was compared with a spiked soil aged for 90d
      in laboratory. Dieldrin and DDX were respectively 18% and 11% less bioavailable
      in contaminated soil relative to spiked soil despite >40yr of aging. Results show
      that TF-SPE can be useful in examining potential risks associated with
      contaminated soils and to test effectiveness of remediation efforts. 

PMID- 24316069
TI  - Changes in the long-term supply of mercury species to the upper mixed waters of a
      recovering lake.
AB  - We quantified internal processes that supply methylmercury from hypolimnetic
      reducing zones to the upper waters of a Hg-contaminated lake, Onondaga Lake, NY,
      USA. Diffusive transport continuously supplied methylmercury to the epilimnion
      under summer stratification, while fall mixing resulted in a pulsed release of
      methylmercury to the upper mixed waters. These processes were the main internal
      sources of methylmercury to the epilimnion, and together almost equaled the total
      external supply. The wind-driven entrainment represented an additional stochastic
      internal supply of methylmercury of approximately 9% in 2006. Considering more
      than 15 years of data, we estimate 1.8 wind-driven events occur per year. The
      mass of methylmercury inputs to the epilimnion exceeded the measured increase,
      suggesting that loss processes are important in regulating methylmercury
      accumulation. The relative contribution of internal sources of methylmercury to
      the epilimnion has decreased in recent years, shifting the importance to the
      external inputs. 

PMID- 24316071
TI  - PD-1 dependent exhaustion of CD8+ T cells drives chronic malaria.
AB  - Malaria is a highly prevalent disease caused by infection by Plasmodium spp.,
      which infect hepatocytes and erythrocytes. Blood-stage infections cause
      devastating symptoms and can persist for years. Antibodies and CD4(+) T cells are
      thought to protect against blood-stage infections. However, there has been
      considerable difficulty in developing an efficacious malaria vaccine,
      highlighting our incomplete understanding of immunity against this disease. Here,
      we used an experimental rodent malaria model to show that PD-1 mediates up to a
      95% reduction in numbers and functional capacity of parasite-specific CD8(+) T
      cells. Furthermore, in contrast to widely held views, parasite-specific CD8(+) T
      cells are required to control both acute and chronic blood-stage disease even
      when parasite-specific antibodies and CD4(+) T cells are present. Our findings
      provide a molecular explanation for chronic malaria that will be relevant to
      future malaria-vaccine design and may need consideration when vaccine development
      for other infections is problematic. 

PMID- 24316070
TI  - Recent advances in molecular, multimodal and theranostic ultrasound imaging.
AB  - Ultrasound (US) imaging is an exquisite tool for the non-invasive and real-time
      diagnosis of many different diseases. In this context, US contrast agents can
      improve lesion delineation, characterization and therapy response evaluation. US
      contrast agents are usually micrometer-sized gas bubbles, stabilized with soft or
      hard shells. By conjugating antibodies to the microbubble (MB) surface, and by
      incorporating diagnostic agents, drugs or nucleic acids into or onto the MB
      shell, molecular, multimodal and theranostic MBs can be generated. We here
      summarize recent advances in molecular, multimodal and theranostic US imaging,
      and introduce concepts how such advanced MB can be generated, applied and imaged.
      Examples are given for their use to image and treat oncological, cardiovascular
      and neurological diseases. Furthermore, we discuss for which therapeutic entities
      incorporation into (or conjugation to) MB is meaningful, and how US-mediated MB
      destruction can increase their extravasation, penetration, internalization and
      efficacy. 

PMID- 24316072
TI  - Transcription factors mediate the enzymatic disassembly of promoter-bound 7SK
      snRNP to locally recruit P-TEFb for transcription elongation.
AB  - The transition from transcription initiation into elongation is controlled by
      transcription factors, which recruit positive transcription elongation factor b
      (P-TEFb) to promoters to phosphorylate RNA polymerase II. A fraction of P-TEFb is
      recruited as part of the inhibitory 7SK small nuclear ribonucleoprotein particle
      (snRNP), which inactivates the kinase and prevents elongation. However, it is
      unclear how P-TEFb is captured from the promoter-bound 7SK snRNP to activate
      elongation. Here, we describe a mechanism by which transcription factors mediate
      the enzymatic release of P-TEFb from the 7SK snRNP at promoters to trigger
      activation in a gene-specific manner. We demonstrate that Tat recruits
      PPM1G/PP2Cgamma to locally disassemble P-TEFb from the 7SK snRNP at the HIV
      promoter via dephosphorylation of the kinase T loop. Similar to Tat, nuclear
      factor (NF)-kappaB recruits PPM1G in a stimulus-dependent manner to activate
      elongation at inflammatory-responsive genes. Recruitment of PPM1G to promoter
      assembled 7SK snRNP provides a paradigm for rapid gene activation through
      transcriptional pause release. 

PMID- 24316073
TI  - Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to
      signal in neuronal primary cilia.
AB  - Human monogenic obesity syndromes, including Bardet-Biedl syndrome (BBS),
      implicate neuronal primary cilia in regulation of energy homeostasis. Cilia in
      hypothalamic neurons have been hypothesized to sense and regulate systemic energy
      status, but the molecular mechanism of this signaling remains unknown. Here, we
      report a comprehensive localization screen of 42 G-protein-coupled receptors
      (GPCR) revealing seven ciliary GPCRs, including the neuropeptide Y (NPY)
      receptors NPY2R and NPY5R. We show that mice modeling BBS disease or obese tubby
      mice fail to localize NPY2R to cilia in the hypothalamus and that BBS mutant mice
      fail to activate c-fos or decrease food intake in response to the NPY2R ligand
      PYY3-36. We find that cells with ciliary NPY2R show augmented PYY3-36-dependent
      cAMP signaling. Our data demonstrate that ciliary targeting of NPY receptors is
      important for controlling energy balance in mammals, revealing a physiologically
      defined ligand-receptor pathway signaling within neuronal cilia. 

PMID- 24316075
TI  - An anti-inflammatory NOD-like receptor is required for microglia development.
AB  - Microglia are phagocytic cells that form the basis of the brain's immune system.
      They derive from primitive macrophages that migrate into the brain during
      embryogenesis, but the genetic control of microglial development remains elusive.
      Starting with a genetic screen in zebrafish, we show that the noncanonical NOD
      like receptor (NLR) nlrc3-like is essential for microglial formation. Although
      most NLRs trigger inflammatory signaling, nlrc3-like acts cell autonomously in
      microglia precursor cells to suppress unwarranted inflammation in the absence of
      overt immune challenge. In nlrc3-like mutants, primitive macrophages initiate a
      systemic inflammatory response with increased proinflammatory cytokines and
      actively aggregate instead of migrating into the brain to form microglia. NLRC3
      like requires both its pyrin and NACHT domains, and it can bind the inflammasome
      component apoptosis-associated speck-like protein. Our studies suggest that NLRC3
      like may regulate the inflammasome and other inflammatory pathways. Together,
      these results demonstrate that NLRC3-like prevents inappropriate macrophage
      activation, thereby allowing normal microglial development. 

PMID- 24316074
TI  - High-throughput genetic screen for synaptogenic factors: identification of LRP6
      as critical for excitatory synapse development.
AB  - Genetic screens in invertebrates have discovered many synaptogenic genes and
      pathways. However, similar genetic studies have not been possible in mammals. We
      have optimized an automated high-throughput platform that employs automated
      liquid handling and imaging of primary mammalian neurons. Using this platform, we
      have screened 3,200 shRNAs targeting 800 proteins. One of the hits identified was
      LRP6, a coreceptor for canonical Wnt ligands. LRP6 regulates excitatory
      synaptogenesis and is selectively localized to excitatory synapses. In vivo
      knockdown of LRP6 leads to a reduction in the number of functional synapses.
      Moreover, we show that the canonical Wnt ligand, Wnt8A, promotes synaptogenesis
      via LRP6. These results provide a proof of principle for using a high-content
      approach to screen for synaptogenic factors in the mammalian nervous system and
      identify and characterize a Wnt ligand receptor complex that is critical for the
      development of functional synapses in vivo. 

PMID- 24316077
TI  - Visual map shifts based on whisker-guided cues in the young mouse visual cortex.
AB  - Mice navigate nearby space using their vision and whiskers, and young mice learn
      to integrate these heterogeneous inputs in perceptual space. We found that
      cortical responses were depressed in the primary visual cortex of young mice
      after wearing a monocular prism. This depression was uniformly observed in the
      primary visual cortex and was eliminated by whisker trimming or lesions in the
      posterior parietal cortex. Compensatory visual map shifts of responses elicited
      via the eye that had worn the prism were also observed. As a result, cortical
      responses elicited via each eye were clearly separated when a visual stimulus was
      placed in front of the mice. A comparison of response areas before and after
      prism wearing indicated that the map shifts were produced by depression with
      spatial eccentricity. Visual map shifts based on whisker-guided cues may serve as
      a model for investigating the cellular and molecular mechanisms underlying higher
      sensory integration in the mammalian brain. 

PMID- 24316076
TI  - Genetic control of the segregation of pain-related sensory neurons innervating
      the cutaneous versus deep tissues.
AB  - Mammalian pain-related sensory neurons are derived from TrkA lineage neurons
      located in the dorsal root ganglion. These neurons project to peripheral targets
      throughout the body, which can be divided into superficial and deep tissues.
      Here, we find that the transcription factor Runx1 is required for the development
      of many epidermis-projecting TrkA lineage neurons. Accordingly, knockout of Runx1
      leads to the selective loss of sensory innervation to the epidermis, whereas deep
      tissue innervation and two types of deep tissue pain are unaffected. Within these
      cutaneous neurons, Runx1 suppresses a large molecular program normally associated
      with sensory neurons that innervate deep tissues, such as muscle and visceral
      organs. Ectopic expression of Runx1 in these deep sensory neurons causes a loss
      of this molecular program and marked deficits in deep tissue pain. Thus, this
      study provides insight into a genetic program controlling the segregation of
      cutaneous versus deep tissue pain pathways. 

PMID- 24316079
TI  - Delayed hepatic adaptation to weaning in ACBP-/- mice is caused by disruption of
      the epidermal barrier.
AB  - We previously reported that mice deficient in acyl-CoA-binding protein (ACBP)
      display a delayed metabolic adaptation to weaning. This includes a delayed
      activation of the hepatic lipogenic gene program, which may result from hepatic
      accumulation of triacylglycerol and/or cholesteryl esters in the late suckling
      period. To further investigate the basis for this phenotype, we generated mice
      deficient in ACBP in hepatocytes (Alb-ACBP(-/-)) and keratinocytes (K14-ACBP(-/
      )). Surprisingly, the delayed adaptation to weaning, including hepatic lipid
      accumulation, is caused by ACBP deficiency in the skin rather than in the liver.
      Similarly to ACBP(-/-) mice, K14-ACBP(-/-) mice exhibit an increased
      transepidermal water loss, and we show that the hepatic phenotype is caused
      specifically by the epidermal barrier defect, which leads to increased lipolysis
      in white adipose tissue. Our data demonstrate that an imperfect epidermal barrier
      leads to profound suppression of the hepatic SREBP gene program and lipid
      accumulation in the liver. 

PMID- 24316078
TI  - TRPV3 channels mediate strontium-induced mouse-egg activation.
AB  - In mammals, calcium influx is required for oocyte maturation and egg activation.
      The molecular identities of the calcium-permeant channels that underlie the
      initiation of embryonic development are not established. Here, we describe a
      transient receptor potential (TRP) ion channel current activated by TRP agonists
      that is absent in TrpV3(-/-) eggs. TRPV3 current is differentially expressed
      during oocyte maturation, reaching a peak of maximum density and activity at
      metaphase of meiosis II (MII), the stage of fertilization. Selective activation
      of TRPV3 channels provokes egg activation by mediating massive calcium entry.
      Widely used to activate eggs, strontium application is known to yield normal
      offspring in combination with somatic cell nuclear transfer. We show that TRPV3
      is required for strontium influx, because TrpV3(-/-) eggs failed to conduct
      Sr(2+) or undergo strontium-induced activation. We propose that TRPV3 is a major
      mediator of calcium influx in mouse eggs and is a putative target for artificial
      egg activation. 

PMID- 24316080
TI  - Dissection of a redox relay: H2O2-dependent activation of the transcription
      factor Pap1 through the peroxidatic Tpx1-thioredoxin cycle.
AB  - In fission yeast, the transcription factor Pap1 undergoes H2O2-dependent
      oxidation that promotes its nuclear accumulation and the activation of an
      antioxidant gene program. However, the mechanisms that regulate the sensitivity
      and selectivity of Pap1 activation by peroxides are not fully understood. Here,
      we demonstrate that the peroxiredoxin Tpx1, the sensor of this signaling cascade,
      activates the otherwise unresponsive Pap1 protein once the main cytosolic reduced
      thioredoxin, Trx1, becomes transiently depleted. In other words, Pap1 works as an
      alternative electron donor for oxidized Tpx1. We have trapped the very transient
      Tpx1-Pap1 intermediate in cells depleted in Trx1, as we show here using mass
      spectrometry. Recycling of Tpx1 by Trx1 is required for the efficient signaling
      to Pap1, suggesting that the complete cycle of H2O2 scavenging by Tpx1 and
      further recycling of oxidized Tpx1 by Trx1 is required for full downstream
      activation of the redox cascade. 

PMID- 24316081
TI  - Testing the iron hypothesis in a mouse model of atherosclerosis.
AB  - Hepcidin, the iron-regulatory hormone and acute phase reactant, is proposed to
      contribute to the pathogenesis of atherosclerosis by promoting iron accumulation
      in plaque macrophages, leading to increased oxidative stress and inflammation in
      the plaque (the "iron hypothesis"). Hepcidin and iron may thus represent
      modifiable risk factors in atherosclerosis. We measured hepcidin expression in
      Apoe(-/-) mice with varying diets and ages. To assess the role of macrophage iron
      in atherosclerosis, we generated Apoe(-/-) mice with macrophage-specific iron
      accumulation by introducing the ferroportin ffe mutation. Macrophage iron loading
      was also enhanced by intravenous iron injection. Contrary to the iron hypothesis,
      we found that hepatic hepcidin expression was not increased at any stage of the
      atherosclerosis progression in Apoe(-/-) or Apoe/ffe mice and that the
      atherosclerotic plaque size was not increased in mice with elevated macrophage
      iron. Our results strongly argue against any significant role of macrophage iron
      in atherosclerosis progression in mice. 

PMID- 24316082
TI  - Structural basis for enhanced HIV-1 neutralization by a dimeric immunoglobulin G
      form of the glycan-recognizing antibody 2G12.
AB  - The human immunoglobulin G (IgG) 2G12 recognizes high-mannose carbohydrates on
      the HIV type 1 (HIV-1) envelope glycoprotein gp120. Its two antigen-binding
      fragments (Fabs) are intramolecularly domain exchanged, resulting in a rigid
      (Fab)2 unit including a third antigen-binding interface not found in antibodies
      with flexible Fab arms. We determined crystal structures of dimeric 2G12 IgG
      created by intermolecular domain exchange, which exhibits increased breadth and
      >50-fold increased neutralization potency compared with monomeric 2G12. The four
      Fab and two fragment crystalline (Fc) regions of dimeric 2G12 were localized at
      low resolution in two independent structures, revealing IgG dimers with two
      (Fab)2 arms analogous to the Fabs of conventional monomeric IgGs. Structures
      revealed three conformationally distinct dimers, demonstrating flexibility of the
      (Fab)2-Fc connections that was confirmed by electron microscopy, small-angle X
      ray scattering, and binding studies. We conclude that intermolecular domain
      exchange, flexibility, and bivalent binding to allow avidity effects are
      responsible for the increased potency and breadth of dimeric 2G12. 

PMID- 24316083
TI  - Pre-operative risk factors of bleeding and stroke during left ventricular assist
      device support: an analysis of more than 900 HeartMate II outpatients.
AB  - OBJECTIVES: This study sought to determine the pre-operative risk factors related
      to late bleeding, stroke, and pump thrombosis in patients with HeartMate II
      (HMII) left ventricular assist devices (LVADs) (Thoratec Corporation, Pleasanton,
      California) that might influence tailored improvements in patient management.
      BACKGROUND: Adverse events in LVAD patients remain high. It is unclear whether
      pre-operative characteristics influence the likelihood of the development of post
      operative hemorrhagic or thrombotic complications. Knowing which patients are at
      greater risk might assist in tailoring anticoagulation therapy for certain
      patients. METHODS: Advanced heart failure patients (n = 956) discharged from the
      hospital after LVAD implantation in the HMII bridge to transplantation (n = 405)
      and destination therapy (n = 551) clinical trials were retrospectively evaluated.
      Bleeding requiring surgery or transfusion of >2 U of packed red blood cells,
      stroke (hemorrhagic and ischemic), and pump thrombosis were tracked from hospital
      discharge until patient outcome. RESULTS: Adverse event rates for post-discharge
      bleeding (0.67 events/patient-year) were higher than those for hemorrhagic stroke
      (0.05), ischemic stroke (0.04), and pump thrombosis (0.03). The main sites of
      bleeding included gastrointestinal (45% of events), wound (12%), and epistaxis
      (4%). Older age (>65 years) (hazard ratio [HR]: 1.31), lower pre-operative
      hematocrit (<=31%) (HR: 1.31), ischemic etiology (HR: 1.35), and female (HR:
      1.45) were statistically significant multivariable risk factors for bleeding.
      Female (HR: 1.92) and 65 years of age and younger (HR: 1.94) were multivariable
      risk factors for hemorrhagic stroke, whereas female (HR: 1.84) and history of
      diabetes (HR: 1.99) were risk factors for ischemic stroke. Female (HR: 1.90) and
      higher body mass index (HR: 1.71/10 kg/m(2) increase) were also multivariable
      risk factors for pump thrombosis. CONCLUSIONS: The risk of bleeding and
      thrombotic events during LVAD support differs by patient demographics, including
      sex, age, body mass index, and etiology of heart failure. Further studies should
      focus on the potential of tailored anticoagulation strategies in these subgroups.

PMID- 24316084
TI  - Acute myocardial infarction caused by infective endocarditis.

PMID- 24316085
TI  - X-shaped secundum atrial septal defect seen by 3-dimensional echocardiography:
      comparison with open-heart view.

PMID- 24316086
TI  - Gross and histological features of excised portions of posterior mitral leaflet
      in patients having operative repair of mitral valve prolapse and comments on the
      concept of missing (= ruptured) chordae tendineae.
AB  - OBJECTIVES: The aim of the study is to describe gross and histological features
      of operatively excised portions of mitral valves in patients with mitral valve
      prolapse (MVP). BACKGROUND: Although numerous articles on MVP (myxomatous or
      myxoid degeneration, billowing or floppy mitral valve) have appeared, 2 virtually
      constant histological features have been underemphasized or overlooked: 1) the
      presence of superimposed fibrous tissue on both surfaces of the leaflets and
      surrounding many chordae tendineae; and 2) the absence of many chordae tendineae
      on the ventricular surfaces of the leaflets as the result of their being hidden
      (i.e., covered up) by the superimposed fibrous tissue. METHODS: We examined
      operatively excised portions of prolapsed posterior mitral leaflets in 37
      patients having operative repair. RESULTS: Histological study of elastic-tissue
      stained sections disclosed that the leaflet thickening was primarily due to the
      superimposed fibrous tissue. All leaflets had variable increases in the spongiosa
      element within the leaflet itself with some disruption and/or loss of the fibrosa
      element and occasionally complete separation of it from the spongiosa element.
      Both the leaflet and chordae were separated from the superimposed fibrous tissue
      by their black-staining elastic membranes. CONCLUSIONS: These findings
      demonstrate that the posterior leaflet thickening in MVP is mainly due to the
      superimposed fibrous tissue rather than to an increased volume of the spongiosa
      element of the leaflet itself. The superimposed fibrous tissue on both leaflet
      and chordae is likely the result of subsequent abnormal contact of the leaflets
      and chordae with one another. Chordal rupture (i.e., missing chordae) occurred in
      all 37 patients, but finding individual ruptured chords was rare.

PMID- 24316087
TI  - The place of new oral anticoagulants in travel medicine.
AB  - New oral anticoagulants are increasingly used instead of vitamin K antagonists or
      low molecular weight heparins. Hence, more individuals treated with new oral
      anticoagulants will seek travel medicine advice. Travel medicine experts should
      therefore become familiar with new oral anticoagulants and with their impact and
      role in travel medicine. This review summarizes pharmacological characteristics
      and approved indications of dabigatran, rivaroxaban and apixaban, and highlights
      their relevance for travellers on permanent oral anticoagulation and for the
      prophylaxis of travellers' thrombosis. Compared to vitamin K antagonists, the new
      oral anticoagulants have many advantages: they do not have interactions with
      food, they have lower potential for drug-drug interactions and do not require
      regularly performed laboratory tests. The oral administration, obviating the need
      to carry needles and syringes during travel may give the new oral anticoagulants
      a further advantage over low molecular weight heparins. Clinical experience with
      the new oral anticoagulants, however, is still rather limited and there is
      concern regarding the clinical management of patients treated with new oral
      anticoagulants who suffer from severe bleeding or who need urgent invasive
      procedures. Overall, it remains an individual decision based on a risk/benefit
      analysis as to whether or not patients on long-term treatment with vitamin K
      antagonists should be switched to new oral anticoagulants for intended travel.
      Further caution is also indicated so that the availability of orally administered
      new anticoagulants should not lead to undifferentiated and unjustified
      prescription of anticoagulants for the prophylaxis of traveller's thrombosis. 

PMID- 24316088
TI  - The effect of the augmentation of cholinergic neurotransmission by nicotine on
      EEG indices of visuospatial attention.
AB  - The cholinergic system has been implicated in visuospatial attention but the
      exact role remains unclear. In visuospatial attention, bias refers to neuronal
      signals that modulate the sensitivity of sensory cortex, while disengagement
      refers to the decoupling of attention making reorienting possible. In the current
      study we investigated the effect of facilitating cholinergic neurotransmission by
      nicotine (Nicorette Freshmint 2mg, polacrilex chewing gum) on behavioral and
      electrophysiological indices of bias and disengagement. Sixteen non-smoking
      participants performed in a Visual Spatial Cueing (VSC) task while EEG was
      recorded. A randomized, single-blind, crossover design was implemented. Based on
      the scarce literature, it was expected that nicotine would specifically augment
      disengagement related processing, especially manifest as an increase of the
      modulation of the Late Positive Deflection (LPD) by validity of cueing. No effect
      was expected on bias related components (cue-locked: EDAN, LDAP; target-locked:
      P1 and N1 modulations). Results show weak indications for a reduction of the
      reaction time validity effect by nicotine, but only for half of the sample in
      which the validity effect on the pretest was largest. Nicotine reduced the result
      of bias as indexed by a reduced P1 modulation by validity, especially in subjects
      with strong peripheral responses to nicotine. Nicotine did not affect ERP
      manifestations of the directing of bias (EDAN, LDAP) or disengagement (LPD). 

PMID- 24316089
TI  - Cutting for stone in augmented bladders-what is the risk of recurrence and is it
      impacted by treatment modality?
AB  - PURPOSE: Bladder stones are common after bladder augmentation, often resulting in
      numerous procedures for recurrence. We sought to determine whether surgical
      technique and stone fragmentation are significant predictors of bladder stone
      recurrence after bladder augmentation. MATERIALS AND METHODS: We retrospectively
      reviewed 107 patients treated for first bladder stones at our institution.
      Patient demographics, details of surgeries, stone therapy and recurrence were
      reviewed. Kaplan-Meier survival and Cox proportional hazards analysis were used
      to determine predictors of time to first stone recurrence. RESULTS: Of 107
      patients 55.1% were female and 79.4% had neuropathic bladder. Patients underwent
      augmentation at a median age of 8.0 years (range 2.4 to 22.8) and were followed
      for a median of 12.4 years (1.8 to 34). Segments used for augmentation included
      ileum (72.9% of cases), sigmoid (16.8%), cecum/ileocecum (9.4%) and other
      (ureter, stomach/ileum, 1.8%). Bladder neck procedures were performed in 63.6% of
      patients and catheterizable channels in 75.7%. First stone surgery occurred at a
      median of 3.1 years after augmentation (range 5 months to 21.8 years). Endoscopy
      was used in 66.4% of cases and open cystolithotomy in 33.6%. Overall 47.7% of
      stones were fragmented. Bladder stones recurred in 47.7% of patients (median
      recurrence time 9.5 years, range 3 months to 14.7 years). Recurrence risk was
      greatest in the first 2 years postoperatively (12.1% per patient per year, p =
      0.03). Recurrence risk did not change with technique (endoscopic vs open) or
      fragmentation, even after controlling for surgical and clinical variables.
      CONCLUSIONS: Bladder stones recurred in almost half of the patients at 9 years
      postoperatively independent of treatment technique and patient characteristics.
      As a high risk group, yearly x-ray of the kidneys, ureters and bladder, and
      ultrasound of the kidneys and bladder are recommended in these patients.

PMID- 24316090
TI  - Reduced flow after tubularized incised plate urethroplasty--increased
      fibrogenesis, elastin fiber loss or neither?
AB  - PURPOSE: Low urinary flow rates are common after tubularized incised plate
      urethroplasty but the etiology remains unclear and may be related to low urethral
      compliance due to abnormal collagen concentrations and/or fewer elastic fibers in
      the healed urethral plate. We hypothesized that inserting a preputial mucosal
      graft over the dorsal raw area after the midline incision may avoid scarring and
      improve urethral compliance. MATERIALS AND METHODS: Adult rabbits were submitted
      to tubularized incised plate urethroplasty with or without inlay preputial graft
      according to a previously described protocol. Tissular concentrations of
      collagens I, III, IV, VI, VIII and XIII were measured. Histomorphometric analysis
      was used to quantify elastic fibers in the urethra. Tubularized incised plate
      urethroplasty with and without inlay preputial graft was compared to normal
      rabbit urethras (controls). RESULTS: mRNA concentrations for collagens I, II and
      XIII were similar between controls and operated rabbits. The proportions between
      collagens I and III were 1.05, 0.87 and 1.21, respectively, in controls and
      animals undergoing tubularized incised plate urethroplasty with and without inlay
      preputial graft. mRNA concentrations for collagen IV and collagens VI/VIII tended
      to be higher and lower, respectively, in the operated urethras, despite showing
      statistical significance only for collagen VIII in animals undergoing tubularized
      incised plate urethroplasty with inlay preputial graft vs controls (p=0.02). The
      operated animals did not demonstrate a reduced number of elastic fibers in the
      urethral tissues compared to controls. CONCLUSIONS: Elastic fiber number and
      distribution were similar between tubularized incised plate urethroplasty cases
      and controls, suggesting that decreased concentrations of elastic fibers do not
      explain the reduced urethral compliance after tubularized incised plate
      urethroplasty. The raw area determined by the dorsal urethral incision
      regenerated after standard tubularized incised plate urethroplasty, while
      cicatrization with fibrosis occurred in correspondence to the grafted areas after
      tubularized incised plate urethroplasty with inlay preputial graft.

PMID- 24316091
TI  - Segmental hyperalgesia to mechanical stimulus in interstitial cystitis/bladder
      pain syndrome: evidence of central sensitization.
AB  - PURPOSE: We investigate if subjects with interstitial cystitis/bladder pain
      syndrome demonstrate mechanical or thermal hyperalgesia, and whether the
      hyperalgesia is segmental or generalized (global). MATERIALS AND METHODS: Ten
      female subjects with interstitial cystitis/bladder pain syndrome and 10 age
      matched female controls without comorbid fibromyalgia or narcotic use were
      recruited for quantitative sensory testing. Using the method of limits, pressure
      pain and heat pain thresholds were measured. Using the method of fixed stimulus,
      the visual analog scale pain experienced was recorded when a fixed
      pressure/temperature was applied. RESULTS: The visual analog scale pain rated by
      female subjects with interstitial cystitis/bladder pain syndrome was
      significantly higher than that rated by female control subjects when a fixed
      mechanical pressure (2 or 4 kg) was applied to the suprapubic (T11) area (p =
      0.028). There was an up shift of the stimulus-response curve, which corresponded
      to the presence of mechanical hyperalgesia in the suprapubic area in interstitial
      cystitis/bladder pain syndrome. However, the visual analog scale pain rated by
      subjects with interstitial cystitis/bladder pain syndrome was not different from
      that rated by controls when a fixed pressure was applied at the other body sites
      (T1 arm, L4 leg, S2-3 sacral). No difference in visual analog scale pain rating
      was noted when a fixed heat stimulus (35C or 37C) was applied to any of the body
      sites tested (T1, T11, L4, S2). There was no difference in pressure pain
      thresholds or thermal pain thresholds between subjects with interstitial
      cystitis/bladder pain syndrome and controls. CONCLUSIONS: Female subjects with
      interstitial cystitis/bladder pain syndrome showed segmental hyperalgesia to
      mechanical pressure stimulation in the suprapubic area (T10-T12). This segmental
      hyperalgesia may be explained in part by spinal central sensitization.

PMID- 24316092
TI  - Value of transition zone biopsy in active surveillance of prostate cancer.
AB  - PURPOSE: For patients on active surveillance there are limited data on transition
      zone sampling upon followup biopsy. We verified the value of transition zone
      biopsy in the active surveillance setting. MATERIALS AND METHODS: Our study
      included 1,059 sets of prostate biopsies from a total of 534 patients on active
      surveillance at the Johns Hopkins Hospital. Each set comprised at least 14 cores
      with 2 or more from the transition zone. Of these men 53 underwent radical
      prostatectomy. RESULTS: Patients with tumors in the peripheral zone as well as
      the transition zone had a higher maximum Gleason score and an increased maximum
      percent of cancer per core than men with tumor in the peripheral or transition
      zone only. In 12 of the 534 patients (2.2%) the tumor on active surveillance
      biopsy was limited to transition zone core(s). Of the 534 patients 11 (2.1%) had
      tumor with a high Gleason score (greater than 6) or extensive involvement
      (greater than 50%) of any core exclusively on transition zone biopsy. However, in
      10 of 15 radical prostatectomy cases (66.7%) with prior positive transition zone
      biopsies the tumors had little or no transition zone component. In addition,
      transition zone status on biopsy had no significant relationship with Gleason
      score, extraprostatic extension or seminal vesicle involvement at radical
      prostatectomy. CONCLUSIONS: Our data suggest that the additional yield is
      sufficiently low to argue against routine transition zone sampling in men
      undergoing followup biopsy on active surveillance. However, further study is
      needed to make definitive recommendations.

PMID- 24316093
TI  - Statistical validation of the shorter-moldwin food sensitivity questionnaire for
      patients with interstitial cystitis/bladder pain syndrome.
AB  - PURPOSE: American Urological Association guidelines suggest dietary changes as
      first line treatment for interstitial cystitis/bladder pain syndrome. We
      previously developed a validated survey instrument to determine which foods,
      beverages and supplements exacerbate the symptoms of this condition. In this
      study we developed a shortened questionnaire that would provide an easily self
      administered food symptom history useful for clinical practice and future
      research. MATERIALS AND METHODS: Using data from our previously validated food
      sensitivity questionnaire we remodeled the original lengthy survey to an
      abbreviated list including the 35 most problematic comestibles. The instrument
      was reviewed by a panel of experts for face and content validity, and tested for
      internal consistency, readability and clarity, and test-retest reliability.
      RESULTS: Of the 124 patients who completed a baseline questionnaire 52 (42%)
      returned the second instrument 1 week after completing the first instrument.
      Internal consistency was high (alpha=0.96). A total of 47 patients (90.4%)
      indicated that they were food sensitive. Questionnaire test-retest reliability
      assessed by the Spearman correlation coefficient ranged from moderate (rho=0.48
      for Equal(r)) to very strong (rho=0.90 for beer). Discrepancies between the
      survey instruments in individual comestibles occurred only 1% of the time.
      CONCLUSIONS: Our short form diet history questionnaire based on a previously
      validated long form is a reliable, newly validated instrument that will help
      identify comestibles associated with interstitial cystitis/bladder pain syndrome
      symptoms. Its brevity makes it simple to administer and useful for dietary
      management in this population.

PMID- 24316094
TI  - Low androgen induced penile maldevelopment involves altered gene expression of
      biomarkers of smooth muscle differentiation and a key enzyme regulating cavernous
      smooth muscle cell tone.
AB  - PURPOSE: We determined the effects of low androgens in the neonatal period on
      biomarkers of smooth muscle cell differentiation, Myh11 and Acta2, and on Pde5A
      expression in the penis. MATERIALS AND METHODS: One-day-old pups were treated
      daily with the gonadotropin-releasing hormone antagonist antide with or without
      dihydrotestosterone for 1 to 6 days. Tissues were collected at age day 7 and at
      adulthood at age 120 days. Penes were examined by quantitative reverse
      transcriptase-polymerase chain reaction, Western blot and immunohistochemistry.
      Testes were assayed for the intratesticular testosterone and steroidogenic
      enzymes Cyp17alpha1 and StAR. RESULTS: Gonadotropin-releasing hormone antagonist
      exposure suppressed the neonatal testicular testosterone surge 70% to 80%.
      Quantitative reverse transcriptase-polymerase chain reaction revealed 80% to 90%
      reductions in Cyp17alpha1 and StAR protein, and 40% to 60% reductions in Myh11
      and ACTA2 as a result of gonadotropin-releasing hormone antagonist compared to
      controls. Dihydrotestosterone co-administration mitigated these decreases.
      Western blot confirmed the Myh11 decrease at the protein level.
      Immunohistochemistry of Acta2 confirmed cavernous smooth muscle cell loss at the
      tissue level. Also, gonadotropin-releasing hormone antagonist exposure decreased
      Pde5a expression and dihydrotestosterone co-administration mitigated the
      decrease. Comparison of data between 2 parts of the penis body (corpora cavernosa
      and corpus spongiosum) showed that antagonist induced decreases in Myh11, Acta2
      and Pde5a expression occurred only in the corpora cavernosa, implying that the
      latter is the target site of low androgen action. CONCLUSIONS: As evidenced by
      gonadotropin-releasing hormone antagonist induced suppression of the neonatal
      testosterone surge and reduced steroidogenesis, low androgens in the neonatal
      period altered gene expression of biomarkers of smooth muscle cell
      differentiation. This led to loss of cavernous smooth muscle cells and
      consequently to penile maldevelopment.

PMID- 24316095
TI  - Overactive bladder and mental health symptoms in recently deployed female
      veterans.
AB  - PURPOSE: We estimate the prevalence of current overactive bladder symptoms in
      recently deployed female veterans, and determine if overactive bladder symptoms
      are associated with problems commonly reported after deployment including mental
      health symptoms and prior sexual assault. MATERIALS AND METHODS: Baseline data
      were analyzed from a nationwide cohort study of urogenital symptoms in female
      veterans. Women returning from deployment to Iraq or Afghanistan in the prior 2
      years and ending military service were eligible. Self-reported data were
      collected by computer assisted telephone interview. Overactive bladder and mental
      health conditions were identified using standardized definitions as well as
      validated urinary and mental health instruments. Associations between overactive
      bladder and depression, post-traumatic stress disorder, anxiety and sexual
      assault were assessed in separate logistic regression models using propensity
      scores to adjust for confounding. RESULTS: The 1,702 participants had a mean (SD)
      age of 31.1 (8.4) years and were racially/ethnically diverse. Overall 375
      participants (22%; 95% CI 20.1, 24.1) reported overactive bladder. Mental health
      outcomes included post-traumatic stress disorder (19%), anxiety (21%), depression
      (10%) and prior sexual assault (27%). All outcomes were associated with
      overactive bladder (adjusted OR 2.7, 95% CI [2.0, 3.6], 2.7 [2.0, 3.5], 2.5 [1.5,
      4.3] and 1.4 [1.1, 1.9], respectively). CONCLUSIONS: Overactive bladder symptoms
      occurred in 22% of recently deployed female veterans, and were associated with
      self-reported mental health symptoms and traumatic events including prior sexual
      assault. Screening and evaluation for bothersome urinary symptoms and mental
      health problems appear warranted in female veterans presenting for primary and
      urological care after deployment.

PMID- 24316096
TI  - Mixed high and low grade bladder tumors--are they clinically high or low grade?
AB  - PURPOSE: The pathological grade of bladder cancer has an immense impact on
      patient treatment and prognosis. While most bladder tumors show pure high or low
      grade patterns, some show a mixed pattern. We explored the incidence and clinical
      significance of this phenomenon. MATERIALS AND METHODS: A total of 642 patients
      with a mean age of 67.5 years underwent transurethral resection of nonmuscle
      invasive bladder tumors between June 1998 and December 2008, including 156 and
      454 with low and high grade lesions, respectively. In 32 patients (5%) mixed
      grade tumors were found, defined as low grade tumors with 10% or less of a high
      grade component. All patients were followed a median of 60 months
      postoperatively. RESULTS: Mean age, the proportion of men and the proportion of
      stages Ta/T1 in patients with mixed grade tumors were between those of the high
      and low grade groups. Five-year recurrence-free survival was similar for high,
      low and mixed grade tumor types (56.9%, 63.8% and 66.4%, respectively, p=0.252).
      Five-year progression-free survival was significantly lower in patients with high
      grade disease (73.9%, p<0.0001) but similar in those with high and mixed grade
      tumors (99% and 96.9%, respectively, p=0.167). Similarly, disease specific
      survival was significantly worse in patients with high grade tumors (p<0.0001)
      but similar in those with high and mixed grade lesions (p=0.679). CONCLUSIONS:
      Mixed grade is found in about 5% of nonmuscle invasive tumors, representing a
      patient group with unique clinical features. The clinical course of patients with
      mixed grade tumors parallels that of patients with low grade tumors.

PMID- 24316097
TI  - Moniliformediquinone induces in vitro and in vivo antitumor activity through
      glutathione involved DNA damage response and mitochondrial stress in human
      hormone refractory prostate cancer.
AB  - PURPOSE: Hormone refractory metastatic prostate cancer is a major obstacle in
      clinical treatment. The key focus of this study was the discovery and development
      of a potential agent for this disease. MATERIALS AND METHODS: Several
      pharmacological and biochemical assays were used to characterize the apoptotic
      signaling pathways of moniliformediquinone, a natural product, in hormone
      refractory metastatic prostate cancer. RESULTS: Moniliformediquinone induced cell
      cycle arrest at the S-phase and subsequent apoptosis in the hormone refractory
      metastatic prostate cancer cell lines PC-3 and DU-145. Further examination showed
      that moniliformediquinone induced a DNA damage response associated with Chk1,
      Chk2, c-Jun and JNK activation. Mitochondrial apoptosis pathways were also
      activated, including loss of mitochondrial membrane potential, cytochrome c
      release, and activation of caspase-9 and 3. The antioxidant and glutathione
      precursor N-acetylcysteine, and the antioxidant TroloxTM completely abolished
      moniliformediquinone induced generation of reactive oxygen species. However, N
      acetylcysteine but not Trolox blocked moniliformediquinone mediated apoptosis and
      related signaling cascades. Further identification showed that
      moniliformediquinone alone did not conjugate glutathione but significantly
      decreased cellular glutathione levels. The in vivo study revealed that
      moniliformediquinone completely inhibited tumor growth with no weight loss.
      CONCLUSIONS: Our data suggest that moniliformediquinone is a potential anticancer
      agent for hormone refractory metastatic prostate cancer by decreasing cellular
      glutathione, leading to a DNA damage response and cell cycle arrest at the S
      phase. Mitochondrial stress also occurs due to moniliformediquinone action
      through loss of mitochondrial membrane potential and cytochrome c release, which
      in turn induce the activation of caspase cascades and apoptotic cell death.

PMID- 24316098
TI  - Development of a gastric retentive system as a sustained-release formulation of
      pranlukast hydrate and its subsequent in vivo verification in human studies.
AB  - Pranlukast hydrate was demonstrated in a human site-of-absorption study to have
      extremely poor absorption properties in the lower gastrointestinal tract. The
      ratios of AUC0-24 in the distal small bowel and colon compared to stomach
      delivery were approximately 1/7 and 1/70, respectively. As a consequence, a
      gastroretentive double-layered tablet formulation (gastric swelling system; GSS),
      consisting of a swelling layer and a drug release layer, was developed for once
      daily dosing. To study the gastric retention of the optimized GSS, an in vivo
      gamma scintigraphic study was carried out in nine healthy volunteers. The transit
      profiles demonstrated that the GSS was retained in the stomach for more than 10h.
      The plasma profile was prolonged, especially following administration after an
      evening meal. The human data validated the design concept and suggest that GSS
      could be a promising approach for the development of sustained-release
      formulation for drugs with a limited absorption window in the upper small bowel. 

PMID- 24316099
TI  - The challenge of establishing, growing and sustaining a large biobank: a personal
      perspective.
AB  - Laboratory medicine professionals have a unique understanding of the wealth that
      biological samples bring to clinical research, and of the need for quality
      standards for the collection, transportation, storage and analytical phases. The
      expertise of laboratory physicians and scientists also adds value to the
      interpretation and publication of the results of clinical research studies. This
      is an account of the evolution of over thirty five years of the Biobank/Clinical
      Research Clinical Trials Laboratory at one Canadian health sciences centre. The
      logistical, financial, and quality management challenges are presented in growing
      from a small-scale facility to one that now stores three million well
      characterized samples from more than seventy countries, representing five
      continents and five major ethnic groups. This is an account of a journey, it is
      not intended as a guide as to how to create an 'ideal' biobank. Collaboration,
      collegiality, consistency, creativity and clinical collaborators, are the keys to
      progress, but there must first be a vision, one that can expand to embrace new
      opportunities. 

PMID- 24316100
TI  - Comparison of high sensitivity troponin T and I assays in the diagnosis of non-ST
      elevation acute myocardial infarction in emergency patients with chest pain.
AB  - OBJECTIVES: Concentrations of troponin measured with high sensitivity troponin
      assays are raised in a number of emergency department (ED) patients; however many
      are not diagnosed with acute myocardial infarction (AMI). Clinical comparisons
      between the early use (2h after presentation) of high sensitivity cardiac
      troponin T (hs-cTnT) and I (hs-cTnI) assays for the diagnosis of AMI have not
      been reported. DESIGN AND METHODS: Early (0 h and 2 h) hs-cTnT and hs-cTnI assay
      results in 1571 ED patients with potential acute coronary syndrome (ACS) without
      ST elevation on electrocardiograph (ECG) were evaluated. The primary outcome was
      diagnosis of index AMI adjudicated by cardiologists using the local cTnI assay
      results taken >=6 h after presentation, ECGs and clinical information. Stored
      samples were later analysed with hs-cTnT and hs-cTnI assays. RESULTS: The ROC
      analysis for AMI (204 patients; 13.0%) for hs-cTnT and hs-cTnI after 2h was 0.95
      (95% CI: 0.94-0.97) and 0.98 (95% CI: 0.97-0.99) respectively. The sensitivity,
      specificity, PLR, and NLR of hs-cTnT and hs-cTnI for AMI after 2h were 94.1% (95%
      CI: 90.0-96.6) and 95.6% (95% CI: 91.8-97.7), 79.0% (95% CI: 76.8-81.1) and 92.5%
      (95% CI: 90.9-93.7), 4.48 (95% CI: 4.02-5.00) and 12.86 (95% CI: 10.51-15.31),
      and 0.07 (95% CI: 0.04-0.13) and 0.05 (95% CI:0.03-0.09) respectively.
      CONCLUSIONS: Exclusion of AMI 2h after presentation in emergency patients with
      possible ACS can be achieved using hs-cTnT or hs-cTnI assays. Significant
      differences in specificity of these assays are relevant and if using the hs-cTnT
      assay, further clinical assessment in a larger proportion of patients would be
      required.

PMID- 24316101
TI  - Validity of establishing pediatric reference intervals based on hospital patient
      data: a comparison of the modified Hoffmann approach to CALIPER reference
      intervals obtained in healthy children.
AB  - OBJECTIVES: To compare pediatric reference intervals calculated using hospital
      based patient data with those calculated using samples collected from healthy
      children in the community as part of the CALIPER study. METHODS: Hospital-based
      data for 13 analytes (calcium, phosphate, iron, ALP, cholesterol, triglycerides,
      creatinine, direct bilirubin, total bilirubin, ALT, AST, albumin and magnesium),
      measured on the Vitros 5600, collected between 2007 and 2011 were obtained. The
      data for each analyte were partitioned by age and gender as previously defined by
      the CALIPER study. Outliers in each partition were removed using the Tukey
      method. The cumulative distribution function (cdf) was then determined for each
      analyte value following which, the inverse cdf values of a standard Gaussian
      distribution were calculated. The analyte values were plotted against the inverse
      cdf of the standard Gaussian distribution. Piece-wise regression determined the
      linear portion of the resulting graph using the statistical software R. Linear
      regression determined an equation for the linear portion in each partition and
      reference intervals were calculated by extrapolating to identify the 2.5th and
      97.5th centiles in each partition based on the inverse cdf values (which would
      correspond to the values -1.96 and 1.96 of the Gaussian distribution). Using the
      90% confidence intervals for the reference intervals defined by CALIPER and the
      Reference Change Value (RCV) as the criteria, these calculated reference
      intervals were compared to those reported previously by CALIPER. Reference
      samples were also measured on the Vitros 5600 analyzer in an attempt to validate
      the calculated reference intervals. RESULTS: In general, the reference intervals
      calculated from hospital-based data were generally wider than those calculated by
      CALIPER. None of the reference intervals calculated using the Hoffmann approach
      fell completely within the 90% confidence intervals calculated by CALIPER.
      CONCLUSIONS: These results suggest that calculating pediatric reference intervals
      from hospital-based data may be useful, as a guide, in some cases but will likely
      not replace the need to establish reference intervals in healthy pediatric
      populations.

PMID- 24316102
TI  - Clinical metabolomics and hematic ADMA predict the future onset of cardiorenal
      syndrome in young grown-up subjects who were born preterm.
AB  - OBJECTIVES: To look for differences in the urinary metabolic profile and in the
      hematic asymmetric dimethylarginine (ADMA) levels between a group of young adults
      born preterm with an extremely low birthweight (<1000 g; ex-ELBW; n=19) and a
      control group of subjects born at term with a weight appropriate for their
      gestational age (AGA; n=13); and to look for a possible correlation between the
      urinary metabolic profile in ex-ELBW and their hematic levels of ADMA. DESIGN AND
      METHODS: Urine samples were analyzed by (1)H nuclear magnetic resonance
      spectroscopy, and then submitted to unsupervised and supervised multivariate
      analysis. Samples of blood were collected and ADMA concentration was assessed by
      high-performance liquid chromatography. RESULTS: Using supervised PLS-DA (partial
      least squares discriminant analysis) model, the authors were able to discriminate
      between ex-ELBW and AGA. Statistically significant differences were detected in
      the ADMA levels between ex-ELBW and AGA (p<0.02). Ex-ELBW metabolic profile
      correlated with ADMA concentrations (r=0.456, p<0.05). Conversely, ADMA levels in
      AGA did not correlated with their metabolic profiles. CONCLUSIONS: This study
      demonstrates the relevance of the metabolomic technique as a predictive tool of
      the metabolic status in ex-ELBW. The relationship between ex-ELBW urinary
      metabolic profile and their blood ADMA levels suggests the presence of a
      subclinical cardio-renal involvement in these subjects.

PMID- 24316103
TI  - Small intestinal CD4+ T-cell lymphoma is a heterogenous entity with common
      pathology features.
AB  - BACKGROUND & AIMS: Little is known about intestinal CD4+ T-cell lymphoma; this
      rare malignancy is misdiagnosed frequently. We evaluated diagnostic criteria and
      factors that might affect its development and outcome. METHODS: In a
      retrospective analysis, we analyzed medical records and intestinal specimens from
      10 patients diagnosed with intestinal CD4+ T-cell lymphoma among 115 consecutive
      patients examined for severe enteropathy with villous atrophy. Samples were
      analyzed by histology, flow cytometry, and comparative genomic hybridization.
      RESULTS: Small-intestine epithelial and lamina propria tissues from patients who
      presented with chronic diarrhea and malnutrition had variable levels of
      infiltration of CD3+ CD4+ T cells. Flow cytometry showed a high frequency of CD4+
      intraepithelial cells, which frequently expressed a specific Vbeta chain. T-cell
      receptor beta clonality was confirmed by DNA sequencing. Two patients had HLA and
      serology results compatible with celiac disease and autoimmune enteropathy,
      respectively. Two patients were found to have antibodies against human T-cell
      leukemia virus and 2 patients had signs of a recent infection with the herpes
      viruses. Comparative genomic hybridization analyses showed heterogeneous
      chromosomal abnormalities. Symptoms were reduced in patients treated with
      steroids (n = 5), but not in patients given purine analogues or chemotherapy.
      Antibodies against CD52 produced clinical and histologic responses in 2 of 2
      patients, whereas severe adverse effects developed in 1 patient. At the latest
      follow-up evaluation, all patients were alive. CONCLUSIONS: There is much
      heterogeneity in the onset and genetic features of intestinal CD4+ T-cell
      lymphomas, despite their common presentation as indolent lymphoproliferations of
      the intestinal mucosa. Patients should be treated with steroids, and possibly
      antibodies against CD52 (for the most aggressive forms of this disorder).

PMID- 24316104
TI  - Diverticular disease is associated with increased risk of subsequent arterial and
      venous thromboembolic events.
AB  - BACKGROUND & AIMS: Diverticular disease and cardiovascular disease share several
      risk factors. Inflammation associated with diverticular disease could predispose
      to cardiovascular disease. We assessed the association between a diagnosis of
      diverticular disease and subsequent arterial and venous thromboembolic events,
      adjusting for related comorbidities to explore a possible causal relationship.
      METHODS: We identified 77,065 incident cases of diverticular disease from 1980
      2011 from Danish nationwide medical registries; these were matched for age and
      sex with 302,572 population comparison cohort members. Individuals with a history
      of cardiovascular disease were excluded. We used Cox proportional hazards
      regression to compute incidence rate ratios, comparing the incidence of acute
      myocardial infarction, stroke, venous thromboembolism, and subarachnoid
      hemorrhage in patients with diverticular disease with those of the population
      cohort members, adjusting for age, sex, obesity, diabetes, hyperlipidemia,
      chronic obstructive pulmonary disease, connective tissue disease, renal disease,
      and treatments and medications. RESULTS: The adjusted incidence rate ratios for
      patients with diverticular disease, compared with population cohort members, were
      1.11 (95% confidence interval [CI], 1.07-1.14) for acute myocardial infarction,
      1.11 (95% CI, 1.08-1.15) for overall stroke, 1.36 (95% CI, 1.30-1.43) for overall
      venous thromboembolism, and 1.27 (95% CI, 1.09-1.48) for subarachnoid hemorrhage.
      The relative risk of each event remained increased after we adjusted for changes
      in aspirin use or for endoscopy or colorectal surgery after the diagnosis of
      diverticular disease. These findings also held after excluding the first year of
      follow-up and limiting the analysis to patients with diverticulitis. CONCLUSIONS:
      On the basis of an analysis of Danish medical registries, a diagnosis of
      diverticular disease is associated with a modest increase in risk of arterial and
      venous thromboembolic events after adjustment for related disorders.

PMID- 24316105
TI  - Prevention of hepatocellular carcinoma resulting from hepatitis B: are we there
      yet?

PMID- 24316106
TI  - Clinical decision support with natural language processing facilitates
      determination of colonoscopy surveillance intervals.
AB  - BACKGROUND & AIMS: With an increased emphasis on improving quality and decreasing
      costs, new tools are needed to improve adherence to evidence-based practices and
      guidelines in endoscopy. We investigated the ability of an automated system that
      uses natural language processing (NLP) and clinical decision support (CDS) to
      facilitate determination of colonoscopy surveillance intervals. METHODS: We
      performed a retrospective study at a single Veterans Administration medical
      center of patients age 40 years and older who had an index outpatient colonoscopy
      from 2002 through 2009 for any indication except surveillance of a previous
      colorectal neoplasia. We analyzed data from 10,798 reports, with 6379 linked to
      pathology results and 300 randomly selected reports. NLP-based CDS surveillance
      intervals were compared with those determined by paired, blinded, manual review.
      The primary outcome was adjusted agreement between manual review and the fully
      automated system. RESULTS: kappa statistical analysis produced a value of 0.74 (P
      < .001) for agreement between the full text annotation and the NLP-based CDS
      system. Fifty-five reports (18.3%; 95% confidence interval, 14.1%-23.2%) differed
      between manual review and CDS recommendations. Of these, NLP error accounted for
      30 (54.5%), incomplete resection of adenomatous tissue accounted for 14 (25.5%),
      and masses observed without biopsy findings of cancer accounted for 4 (7.2%). NLP
      based CDS surveillance intervals had higher levels of agreement with the standard
      (81.7%) than the level agreement between experts (72% agreement between paired
      reviewers). CONCLUSIONS: A fully automated system that uses NLP and a guideline
      based CSD system can accurately facilitate guideline-recommended adherence
      surveillance for colonoscopy.

PMID- 24316108
TI  - Partner choice promotes cooperation: the two faces of testing with agent-based
      models.
AB  - Reciprocity is one of the most debated among the mechanisms that have been
      proposed to explain the evolution of cooperation. While a distinction can be made
      between two general processes that can underlie reciprocation (within-pair
      temporal relations between cooperative events, and partner choice based on
      benefits received), theoretical modelling has concentrated on the former, while
      the latter has been often neglected. We developed a set of agent-based models in
      which agents adopted a strategy of obligate cooperation and partner choice based
      on benefits received. Our models tested the ability of partner choice both to
      reproduce significant emergent features of cooperation in group living animals
      and to promote the evolution of cooperation. Populations formed by agents
      adopting a strategy of obligate cooperation and partner choice based on benefits
      received showed differentiated "social relationships" and a positive correlation
      between cooperation given and received, two common phenomena in animal
      cooperation. When selection across multiple generations was added to the model,
      agents adopting a strategy of partner choice based on benefits received
      outperformed selfish agents that did not cooperate. Our results suggest partner
      choice is a significant aspect of cooperation and provides a possible mechanism
      for its evolution. 

PMID- 24316107
TI  - Discovery and development of antisecretory drugs for treating diarrheal diseases.
AB  - Diarrheal diseases constitute a significant global health burden and are a major
      cause of childhood mortality and morbidity. Treatment of diarrheal disease has
      centered on the replacement of fluid and electrolyte losses using oral
      rehydration solutions. Although oral rehydration solutions have been highly
      successful, significant mortality and morbidity due to diarrheal disease remains.
      Secretory diarrheas, such as those caused by bacterial and viral enterotoxins,
      result from activation of cyclic nucleotide and/or Ca(2+) signaling pathways in
      intestinal epithelial cells, enterocytes, which increase the permeability of Cl(
      ) channels at the lumen-facing membrane. Additionally, there is often a parallel
      reduction in intestinal Na(+) absorption. Inhibition of enterocyte Cl(-)
      channels, including the cystic fibrosis transmembrane conductance regulator and
      Ca(2+)-activated Cl(-) channels, represents an attractive strategy for
      antisecretory drug therapy. High-throughput screening of synthetic small-molecule
      collections has identified several classes of Cl(-) channel inhibitors that show
      efficacy in animal models of diarrhea but remain to be tested clinically. In
      addition, several natural product extracts with Cl(-) channel inhibition activity
      have shown efficacy in diarrhea models. However, a number of challenges remain to
      translate the promising bench science into clinically useful therapeutics,
      including efficiently targeting orally administered drugs to enterocytes during
      diarrhea, funding development costs, and carrying out informative clinical
      trials. Nonetheless, Cl(-) channel inhibitors may prove to be effective
      adjunctive therapy in a broad spectrum of clinical diarrheas, including acute
      infectious and drug-related diarrheas, short bowel syndrome, and congenital
      enteropathies. 

PMID- 24316109
TI  - Random diffusion and cooperation in continuous two-dimensional space.
AB  - This work presents a systematic study of population games of the Prisoner's
      Dilemma, Hawk-Dove, and Stag Hunt types in two-dimensional Euclidean space under
      two-person, one-shot game-theoretic interactions, and in the presence of agent
      random mobility. The goal is to investigate whether cooperation can evolve and be
      stable when agents can move randomly in continuous space. When the agents all
      have the same constant velocity cooperation may evolve if the agents update their
      strategies imitating the most successful neighbor. If a fitness difference
      proportional is used instead, cooperation does not improve with respect to the
      static random geometric graph case. When viscosity effects set-in and agent
      velocity becomes a quickly decreasing function of the number of neighbors they
      have, one observes the formation of monomorphic stable clusters of cooperators or
      defectors in the Prisoner's Dilemma. However, cooperation does not spread in the
      population as in the constant velocity case. 

PMID- 24316111
TI  - Advanced age is not a contraindication for liver resection in cases of large
      hepatocellular carcinoma.
AB  - BACKGROUND: The role of surgery in the management of large hepatocellular
      carcinomas (HCCs) is controversial. Advanced age and comorbidities are taken into
      account when major surgery is considered. PURPOSE: To compare the outcomes of
      liver resection (LR) and transarterial chemoembolization (TACE) for resectable
      HCC in patients aged 70 years or older. PATIENTS AND MATERIALS: This study
      included 70 patients aged 70 years or older treated for large HCCs (>=5 cm)
      between January 2007 and December 2012: 37 underwent LR and 33 underwent TACE.
      The outcomes of these patients were retrospectively analyzed. Univariate and
      multivariate Cox proportional hazard models were established. Kaplan-Meier
      survival curves were generated, and survival data were compared using the log
      rank test. RESULTS: Hospital stay was significantly longer in the LR group than
      in the TACE group (10 days vs 8.5 days; P = 0.003). Treatment-related
      complications were more frequent in the TACE group, but this difference was not
      statistically significant. LR was associated with a better disease-free survival
      rate, median survival rate and cumulative overall survival rate. CONCLUSION: Our
      results showed that LR could be a safe and effective treatment option for HCC
      tumors >=5 cm in patiets aged 70 years or older.

PMID- 24316112
TI  - Alteration of the intrinsic apoptosis pathway is involved in Notch-induced
      chemoresistance to gemcitabine in pancreatic cancer.
AB  - BACKGROUND AND AIMS: Chemoresistance is a major challenge in pancreatic cancer
      (PC) treatment. Limited data have shown that members of the Notch signaling
      pathway are involved in resistance to gemcitabine (GEM) in PC. However, further
      evidence is needed and the underlying mechanisms remain to be elucidated. The
      current study aims to investigate the role of alterations of the intrinsic
      apoptosis pathway in Notch-induced GEM resistance of PC. METHODS: The Notch
      signaling pathway was inhibited or activated in three PC cell lines (AsPC-1, BxPC
      3, and MIA PaCa-2) by gamma-secretase inhibition and Notch intracellular domain
      (NICD) overexpression, respectively. Subsequent analyses included inhibition
      rates of cell proliferation by GEM, cell apoptosis, and expression of proteins
      involved in the intrinsic apoptosis pathway. RESULTS: Hes-1 expression was
      significantly elevated after GEM treatment, indicating Notch activation.
      Inhibition of the Notch signaling pathway by DAPT, a gamma-secretase inhibitor,
      resulted in a significant increase of the inhibition rates by GEM in all PC cell
      lines. In addition, there was more frequent apoptosis, higher caspase-3 activity,
      up-regulation of Bax, and down-regulation of Bcl-2 and Bcl-xL. Conversely,
      transient transfection of NICD, which enhances the activity of the Notch
      signaling, caused a remarkable decrease of the chemosensitivity to GEM.
      CONCLUSIONS: An alteration of the intrinsic apoptosis pathway is involved in
      Notch-induced chemoresistance to GEM in PC cells.

PMID- 24316113
TI  - Activities of neutrophil membrane-bound proteases in type 2 diabetic patients.
AB  - BACKGROUND AND AIMS: Hyperglycemia and oxidative stress in type 2 diabetes (T2DM)
      provoke neutrophil overstimulation and the release and/or translocation of
      proteases from granules to the cell surface. Although the expression of
      neutrophil membrane-bound elastase (MLE) is well documented, the presence of the
      membrane-bound form of cathepsin B (MCB) is unknown. The aim of our study was to
      evaluate the neutrophil MLE and MCB activities in T2DM patients and their
      associations with the metabolic and clinical parameters of the disease. METHODS:
      Neutrophils were obtained from 47 T2DM patients and 20 control subjects. The
      activities of MLE and MCB and the intracellular activities of the examined
      proteases (ILE and ICB, respectively) were measured using fluorometric
      substrates. Additionally, the percentage equivalents of the activities, namely,
      MLEtot/ILEtot and MCBtot/ICBtot, were calculated. The susceptibility to
      inhibitors of both forms of the studied proteases was also determined. RESULTS: A
      significant increase in the activities of MLE, MCB, ILE, and ICB was found in
      neutrophils from T2DM patients compared with the control group. The percentage
      equivalent (contribution of the total membrane-bound activities to the total
      intracellular activities) was also higher. A partial resistance of the membrane
      bound forms toward their inhibitors was revealed. Higher activities of both the
      membrane-bound and the intracellular proteases were also observed in patients
      with poor glycemic and metabolic control. The differences between subgroups with
      different therapeutic schemes were also revealed. CONCLUSIONS: The
      pathophysiological implications of the neutrophil membrane-bound forms of
      leukocyte elastase and cathepsin B are of great importance in the development of
      T2DM and its complications.

PMID- 24316110
TI  - Innate immune activation in the pathogenesis of a murine model of globoid cell
      leukodystrophy.
AB  - Globoid cell leukodystrophy is a lysosomal storage disease characterized by the
      loss of galactocerebrosidase. Galactocerebrosidase loss leads to the accumulation
      of psychosine and subsequent oligodendrocyte cell death, demyelination,
      macrophage recruitment, and astroglial activation and proliferation. To date, no
      studies have elucidated the mechanism of glial cell activation and cytokine and
      chemokine up-regulation and release. We explored a novel explanation for the
      development of the pathological changes in the early stages of globoid cell
      leukodystrophy associated with toll-like receptor (TLR) 2 up-regulation in the
      hindbrain and cerebellum as a response to dying oligodendrocytes. TLR2 up
      regulation on microglia/macrophages coincided with morphological changes
      consistent with activation at 2 and 3 weeks of age. TLR2 up-regulation on
      activated microglia/macrophages resulted in astrocyte activation and marked up
      regulation of cytokines/chemokines. Because oligodendrocyte cell death is an
      important feature of globoid cell leukodystrophy, we tested the ability of TLR2
      reporter cells to respond to oligodendrocyte cell death. These reporter cells
      responded in vitro to medium conditioned by psychosine-treated oligodendrocytes,
      indicating the likelihood that oligodendrocytes release a TLR2 ligand during
      apoptosis. TLRs are a member of the innate immune system and initiate immune and
      inflammatory events; therefore, the identification of TLR2 as a potential driver
      in the activation of central nervous system glial activity in globoid cell
      leukodystrophy may provide important insight into its pathogenesis. 

PMID- 24316114
TI  - A multisubstrate assay for lipases/esterases: assessing acyl chain length
      selectivity by reverse-phase high-performance liquid chromatography.
AB  - Lipases and esterases are hydrolytic enzymes and are known to hydrolyze esters
      with unique substrate specificity and acyl chain length selectivity. We have
      developed a simple competitive multiple substrate assay for determination of acyl
      chain length selectivity of lipases/esterases using RP-HPLC with UV detection. A
      method for separation and quantification of 4-nitrophenyl fatty acid esters (C4
      C18) was developed and validated. The chain length selectivity of five lipases
      and two esterases was determined in a multisubstrate reaction system containing
      equimolar concentrations of 4-nitrophenyl esters (C4-C18). This assay is simple,
      reproducible, and a useful tool for determining chain length selectivity of
      lipases/esterases. 

PMID- 24316115
TI  - Measurement of downstream kinase activity modulation as indicator of epidermal
      growth factor receptor inhibitor efficacy.
AB  - The acoustic membrane micro particle (AMMP) technology has been used to quantify
      single analytes out of multiple sample types. In this study the technology is
      used to reveal molecular interactions of components of kinase pathways.
      Specifically, the downstream kinase activity of the EGFR receptor in the presence
      or absence of EGFR inhibitors is investigated. These experiments substantiate
      that EGFR stimulation predominantly activates the MEK/ERK pathway. The EGFR
      inhibitors tested had varying effectiveness at preventing phosphorylation at the
      EGFR or downstream kinase activity. These experiments reveal the use of the AMMP
      technology for observing multiple signaling pathways in a single experiment. 

PMID- 24316116
TI  - Vertebral compression fractures in patients under treatment with denosumab: a
      contraindication for percutaneous vertebroplasty?
AB  - BACKGROUND CONTEXT: Denosumab (XGeva) is a receptor activator of nuclear factor
      kappaB ligand (RANKL)-antibody that was approved by the Food and Drug
      Administration (FDA) in 2010 for the prevention of skeletal fractures in patients
      with bone metastases from solid tumors. Although there is a widespread use of
      such drug in patients under risk of pathological fractures, the compatibility of
      denosumab therapy with percutaneous vertebroplasty (an interventional procedure
      commonly used for pain control in such population) has not yet been established.
      PURPOSE: To present the serial imaging findings and technical report of an
      attempted percutaneous vertebroplasty in a patient with refractory pain and a
      lytic pathological vertebral fracture related to small cell lung cancer spinal
      metastasis and who was actively under medical treatment with denosumab. STUDY
      DESIGN: Retrospective review and case report. METHODS: The authors present the
      imaging findings and technical report of an attempted percutaneous vertebroplasty
      in the only patient found to be actively under treatment with denosumab after a
      retrospective review of the databank of patients with pathological fractures
      referred to the Department of Radiology of the Ohio State University for
      percutaneous vertebroplasty (a total sample of 20 patients) since the FDA
      approval of denosumab (November 2010) until June 2013 (a 30-month period).
      RESULTS: Although the computed tomography scan of the thoracic spine, performed 6
      weeks after the initiation of the treatment with denosumab, presented a
      remarkable remodeling of the previously lytic vertebral lesion (which became
      markedly sclerotic in appearance), the clinical response in terms of pain
      improvement was not satisfactory. At the time of the percutaneous vertebroplasty
      (which was indicated for pain control), after advancing the 11-gauge needle
      through the pedicle with extreme difficulty, the needle repeatedly deviated
      laterally and, despite several attempts, it was not possible to penetrate the
      vertebral body and perform the cement injection. CONCLUSIONS: This is the first
      report of the technical peculiarities of percutaneous vertebroplasty in patients
      under medical treatment with denosumab. According to our experience, because of
      its RANKL-mediated effects on osteoclasts activity, denosumab has been shown to
      induce a fast and marked sclerotic response on vertebral bodies that may not be
      accompanied by a satisfactory improvement in pain control (especially in patients
      with mechanical type of pain) and which may actually prevent the successful
      performance of percutaneous vertebroplasty. Therefore, it is of paramount
      importance that future studies evaluating patients with vertebral fractures under
      treatment with denosumab include long-term pain outcome measures. Additionally,
      further investigation is warranted to determine the optimal order of treatment
      and the best timeframe for combining percutaneous vertebroplasty and denosumab
      therapy in patients presenting with acute vertebral compression fractures and
      refractory axial pain.

PMID- 24316117
TI  - Symptomatic spinal epidural hematoma after posterior cervical surgery: incidence
      and risk factors.
AB  - BACKGROUND CONTEXT: The true incidence of symptomatic spinal epidural hematoma
      (SEH) after surgery of the posterior cervical spine and risk factors for its
      development remain unclear. PURPOSE: The purpose of this study was to determine
      the 10-year incidence of symptomatic postoperative SEH and identify risk factors
      for its development. STUDY DESIGN/SETTING: This study is a retrospective
      observational study at a Canadian tertiary care spine center. PATIENT SAMPLE: The
      study sample includes adult patients undergoing posterior surgery of the cervical
      spine. OUTCOME MEASURES: The outcome measures were the incidence of symptomatic
      postoperative SEH and risk factors for its development. METHODS: Surgical
      procedure codes were used to identify study candidates. Using a standard data
      collection form, two independent reviewers manually searched paper and electronic
      medical records to extract patient-, treatment-, and complication-related data.
      Time to presentation, clinical findings, method of treatment, and intraoperative
      findings (when relevant) were recorded for patients with an SEH. The overall
      incidence of symptomatic SEH was calculated, and the categorical and continuous
      variables were summarized with percentages and means, respectively. Stepwise
      forward selection logistic regression analysis was performed to identify risk
      factors for the development of symptomatic SEH. RESULTS: From January 2002 to
      December 2011, 529 patients (356 men and 173 women; mean age, 56.7 years) were
      identified for study inclusion. The mean Charlson Comorbidity Index (CCI) was
      0.65 (range, 0-8). Myelopathy was the most common surgical indication (n=293;
      55.4%), with the largest subset of patients undergoing decompression with or
      without instrumented fusion (n=266; 50.3%). Symptomatic postoperative SEH was
      diagnosed in eight patients for an overall incidence of 1.5%. Postoperative
      nonsteroidal anti-inflammatory drug (NSAID) use and an increased CCI were
      identified as significant predictors of the development of a symptomatic SEH in
      our study cohort (p=.024 and .003, respectively). When all other variables
      remained constant, a 1-point increase in CCI was associated with 1.6 times higher
      odds of hematoma development, whereas postoperative NSAID use increased the odds
      6.6 times. CONCLUSIONS: Symptomatic SEH may occur in up to 1.5% of patients
      undergoing posterior cervical spine surgery. Patients with a higher level of
      comorbid disease appear to be at increased risk of development of a symptomatic
      SEH, although avoidance of postoperative NSAIDs may decrease the risk of its
      development.

PMID- 24316118
TI  - Obese Class III patients at significantly greater risk of multiple complications
      after lumbar surgery: an analysis of 10,387 patients in the ACS NSQIP database.
AB  - BACKGROUND CONTEXT: Prior studies on the impact of obesity on spine surgery
      outcomes have focused mostly on lumbar fusions, do not examine lumbar
      discectomies or decompressions, and have shown mixed results regarding
      complications. Differences in sample sizes and body mass index (BMI) thresholds
      for the definition of the obese versus comparison cohorts could account for the
      inconsistencies in the literature. PURPOSE: The purpose of the study was to
      analyze whether different degrees of obesity influence the complication rates in
      patients undergoing lumbar spine surgery. STUDY DESIGN/SETTING: This was a
      retrospective cohort analysis of prospectively collected data using the American
      College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP)
      database from 2005 to 2010. PATIENT SAMPLE: Patients in the de-identified, risk
      adjusted, and multi-institutional ACS NSQIP database undergoing lumbar anterior
      fusion, posterior fusion, transforaminal lumbar interbody fusion/posterior lumbar
      interbody fusion (TLIF/PLIF), discectomy, or decompression were included. OUTCOME
      MEASURES: Primary outcome measures were 30-day postsurgical complications,
      including pulmonary embolism and deep vein thrombosis, death, system-specific
      complications (wound, pulmonary, urinary, central nervous system, and cardiac),
      septic complications, and having one or more complications overall. Secondary
      outcomes were time spent in the operating room, blood transfusions, length of
      stay, and reoperation within 30 days. METHODS: Patients undergoing lumbar
      anterior fusion, posterior fusion, TLIF/PLIF, discectomy, or decompression in the
      ACS NSQIP, 2005 to 2010, were categorized into four BMI groups: nonobese (18.5
      29.9 kg/m(2)), Obese I (30-34.9 kg/m(2)), Obese II (35-39.9 kg/m(2)), and Obese
      III (greater than or equal to 40 kg/m(2)). Obese I to III patients were compared
      with patients in the nonobese category using chi-square test and analysis of
      variance. Multivariate linear/logistic regression models were used to adjust for
      preoperative risk factors. RESULTS: Data were available for 10,387 patients
      undergoing lumbar surgery. Of these, 4.5% underwent anterior fusion, 17.9%
      posterior fusion, 6.3% TLIF/PLIF, 40.7% discectomy, and 30.5% decompression.
      Among all patients, 25.6% were in the Obese I group, 11.5% Obese II, and 6.9%
      Obese III. On multivariate analysis, Obese I and III had a significantly
      increased risk of urinary complications, and Obese II and III patients had a
      significantly increased risk of wound complications. Only Obese III patients,
      however, had a statistically increased risk of having increased time spent in the
      operating room, an extended length of stay, pulmonary complications, and having
      one or more complications (all p<.05). CONCLUSIONS: Patients with high BMI appear
      to have higher complication rates after lumbar surgery than patients who are
      nonobese. However, the complication rates seem to increase substantially for
      Obese III patients. These patients have longer times spent in the operating room,
      extended hospitals stays, and an increased risk for wound, urinary, and pulmonary
      complications and for having at least one or more complications overall. Surgeons
      should be aware of the increased risk of multiple complications for patients with
      BMI greater than or equal to 40 kg/m(2).

PMID- 24316119
TI  - Parental perception of the nutritional quality of school meals and its
      association with students' school lunch participation.
AB  - This study explores the association between parental perception of the
      nutritional quality of school meals and whether students eat lunch served at
      school. We use data from five low-income cities in New Jersey that have high
      minority populations. Students whose parents perceive the quality of school meals
      to be healthy have greater odds of eating meals served at school. Recent changes
      in guidelines for the United States Department of Agriculture's National School
      Lunch Program met with resistance from several fronts. Advocates for and
      implementers of improved school meals may benefit from partnering with parents to
      increase the acceptance and utilization of improved school offerings. 

PMID- 24316120
TI  - Partner support and impact on birth outcomes among teen pregnancies in the United
      States.
AB  - PURPOSE: Despite hypothesized relationships between lack of partner support
      during a woman's pregnancy and adverse birth outcomes, few studies have examined
      partner support among teens. We examined a potential proxy measure of partner
      support and its impact on adverse birth outcomes (low birth weight (LBW), preterm
      birth (PTB) and pregnancy loss) among women who have had a teenage pregnancy in
      the United States. METHODS: In a secondary data analysis utilizing cross
      sectional data from 5609 women who experienced a teen pregnancy from the 2006
      2010 National Survey of Family Growth (NSFG), we examined an alternative measure
      of partner support and its impact on adverse birth outcomes. Bivariate and
      multivariable logistic regression were used to assess differences in women who
      were teens at time of conception who had partner support during their pregnancy
      and those who did not, and their birth outcomes. RESULTS: Even after controlling
      for potential confounding factors, women with a supportive partner were 63% less
      likely to experience LBW [aOR: 0.37, 95% CI: (0.26-0.54)] and nearly 2 times less
      likely to have pregnancy loss [aOR: 0.48, 95% CI: (0.32-0.72)] compared to those
      with no partner support. CONCLUSIONS: Having partner support or involvement
      during a teenager's pregnancy may reduce the likelihood of having a poor birth
      outcome.

PMID- 24316121
TI  - Linker modification reduced the renal uptake of technetium-99m-labeled Arg-Ala
      Asp-conjugated alpha-melanocyte stimulating hormone peptide.
AB  - The purpose of this study was to examine the biodistribution of (99m)Tc-RAD-Arg
      (Arg(11))CCMSH in B16/F1 melanoma-bearing C57 mice to determine whether the
      replacement of the Lys linker with an Arg linker could decrease the renal uptake
      of (99m)Tc-RAD-Arg-(Arg(11))CCMSH. (99m)Tc-RAD-Arg-(Arg(11))CCMSH exhibited rapid
      and high tumor uptake (17.98+/-4.96% ID/g at 2h post-injection) in B16/F1
      melanoma-bearing C57 mice. As compared to (99m)Tc-RAD-Lys-(Arg(11))CCMSH, the
      replacement of the Lys linker with an Arg linker dramatically decreased the renal
      uptake of (99m)Tc-RAD-Arg-(Arg(11))CCMSH by 68%, 62%, 73% and 64% at 0.5, 2, 4
      and 24h post-injection, respectively. Flank B16/F1 melanoma lesions were clearly
      imaged at 2h post-injection using (99m)Tc-RAD-Arg-(Arg(11))CCMSH as an imaging
      probe. 

PMID- 24316122
TI  - Sulfonamide inhibition studies of the gamma-carbonic anhydrase from the oral
      pathogen Porphyromonas gingivalis.
AB  - A carbonic anhydrase (CA, EC 4.2.1.1) denominated PgiCA, belonging to the gamma
      class, from the oral pathogenic bacteria Porphyromonas gingivalis, the main
      causative agent of periodontitis, was investigated for its inhibition profile
      with sulfonamides and one sulfamate. Dichlorophenamide, topiramate and many
      simple aromatic/heterocyclic sulfonamides were ineffective as PgiCA inhibitors
      whereas the best inhibition was observed with halogenosulfanilamides
      incorporating heavy halogens, 4-hydroxy- and 4-hydroxyalkyl-benzenesulfonamides,
      acetazolamide, methazolamide, zonisamide, indisulam, celecoxib, saccharin and
      hydrochlorothiazide (KIs in the range of 131-380nM). The inhibition profile of
      PgiCA was very different from that of CAM, hCA I and II or the beta-CA from a
      protozoan parasite (Leishmania donovani chagasii). Identification of potent and
      possibly selective inhibitors of PgiCA may lead to pharmacological tools useful
      for understanding the physiological role(s) of this enzyme. 

PMID- 24316123
TI  - Novel pyrazole integrated 1,3,4-oxadiazoles: synthesis, characterization and
      antimicrobial evaluation.
AB  - A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4
      oxadiazoles 7(a-m) were synthesized either by cyclization of N'-benzoyl-5-methyl
      1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl3 at 120 degrees C or by
      oxidative cyclization of hydrazones derived from various arylaldehyde and (E)-N'
      benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 5(a-d) using
      chloramine-T as oxidant. Newly synthesized compounds were characterized by
      analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods. The
      synthesized compounds were evaluated for their antimicrobial activity and were
      compared with standard drugs. The compounds demonstrated potent to weak
      antimicrobial activity. Among the synthesized compounds, compound 7m emerged as
      an effective antimicrobial agent, while compounds 7d, 7f, 7i and 7l showed good
      to moderate activity. The minimum inhibitory concentration of the compounds was
      in the range of 20-50MUgmL(-1) against bacteria and 25-55MUgmL(-1) against fungi.
      The title compounds represent a novel class of potent antimicrobial agents. 

PMID- 24316124
TI  - Synthesis of licochalcone analogues with increased anti-inflammatory activity.
AB  - Licohalcones have been reported to have various biological activities. However,
      most of licochalcones also showed cytotoxicity even though their versitile
      utilities. Licochalcones B and D, which have common substituents at aromatic ring
      B, are targeted to modify the structure at aromatic ring A for inflammatory
      studies. Licochalcone derivatives (1-6) thus prepared are compared for their
      suppression ability of nitric oxide (NO) production and showed 9.94, 4.72, 10.1,
      4.85, 2.37 and 4.95MUM of IC50 values, respectively. 

PMID- 24316125
TI  - Three novel homozygous mutations in the GNPTG gene that cause mucolipidosis type
      III gamma.
AB  - BACKGROUND: Mucolipidosis type III gamma (MLIII gamma) is an autosomal recessive
      disease caused by a mutation in the GNPTG gene, which encodes the gamma subunit
      of the N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase).
      This protein plays a key role in the transport of lysosomal hydrolases to the
      lysosome. METHODS: Three Chinese children with typical skeletal abnormalities of
      MLIII were identified, who were from unrelated consanguineous families. After
      obtaining informed consent, genomic DNA was isolated from the patients and their
      parents. Direct sequencing of the GNPTG and GNPTAB genes was performed using
      standard PCR reactions. RESULTS: The three probands showed clinical features
      typical of MLIII gamma, such as joint stiffness and vertebral scoliosis without
      coarsened facial features. Mutation analysis of the GNPTG gene showed that three
      novel mutations were identified, two in exon seven [c.425G>A (p.Cys142Val)] and
      [c.515dupC (p.His172Profs27X)], and one in exon eight [c.609+1G>C]. Their parents
      were determined to be heterozygous carriers when compared to the reference
      sequence in GenBank on NCBI. CONCLUSIONS: Mutation of the GNPTG gene is the cause
      of MLIII gamma in our patients. Our findings expand the mutation spectrum of the
      GNPTG gene and extend the knowledge of the phenotype-genotype correlation of the
      disease.

PMID- 24316126
TI  - Genome-guided analysis of transformation efficiency and carbon dioxide
      assimilation by Moorella thermoacetica Y72.
AB  - We determined a draft genome sequence for Moorella thermoacetica strain Y72, a
      syngas-assimilating bacterium with high transformation efficiency. This strain
      was confirmed to be M. thermoacetica because its overall genome sequence
      characteristics were similar to those of M. thermoacetica strain ATCC39073. Y72
      was confirmed to carry all the genes encoding the enzymes in the reductive acetyl
      CoA pathway, with very high similarities to those of ATCC39073. In addition, it
      was confirmed to assimilate carbon dioxide using this pathway. However, although
      both Y72 and ATCC39073 carried common genes encoding several enzymes related to
      the reductive tricarboxylic acid (TCA) cycle, their gene sets were different. Our
      results suggested that the reason for higher transformation efficiency in Y72
      than that in ATCC39073, a reference strain of M. thermoacetica, may be that Y72
      possesses only 2 sets of genes considered to be involved in a restriction
      modification system, which was half of those found in ATCC39073.

PMID- 24316127
TI  - The Cytochrome P4501A1 gene polymorphisms and idiopathic male infertility risk: a
      meta-analysis.
AB  - Studies of the relationship between male infertility and CYP1A1 polymorphisms are
      inconclusive. To drive a more precise estimation, we performed a meta-analysis
      based on 1060 cases and 1225 controls from 7 published case-control studies.
      PubMed and CNKI literature search were conducted to identify all eligible studies
      investigating such a relationship. Crude odds ratios (ORs) with 95% confidence
      intervals (CIs) were used to assess the strength of association in the additive
      model, dominant model, recessive model, and allele-frequency genetic model. In
      the overall analysis, the frequency of CYP1A12A genotype was significantly
      associated with susceptibility to idiopathic male infertility. Further stratified
      analysis by ethnicity showed notable association between the polymorphism and the
      risk of idiopathic male infertility in Asians. In conclusion, these results
      support that the CYP1A1 2A genotype polymorphism mainly contributes to idiopathic
      male infertility susceptibility in Asians but not in Caucasians.

PMID- 24316128
TI  - Associations of MYH3 gene copy number variations with transcriptional expression
      and growth traits in Chinese cattle.
AB  - Copy number variations (CNVs) have been recently recognized as another important
      genetic variability complementary to single nucleotide polymorphisms (SNPs).
      Compelling evidence has indicated that CNVs are responsible for phenotypic traits
      by changing the copy numbers of functional genes. Myosin heavy chain 3 (MYH3)
      gene is a critical regulatory factor in skeletal muscle development, and has been
      detected in the CNVs region by comparative genomic hybridization (CGH) array.
      This study was conducted to validate and detect the distribution of MYH3 copy
      numbers (relative to Angus cattle) in four Chinese cattle breeds (NY, QC, LX, and
      CY), and further to investigate the associations of the copy number changes with
      its transcriptional expression and cattle growth traits. Substantial genetic
      differences of MYH3 copy numbers were identified between NY and the other three
      breeds (P<0.01). The copy numbers of MYH3 gene presented the positive
      correlations with the transcript level of MYH3 gene in both fetal and adult
      skeletal muscles (P<0.05). Statistical analysis revealed that CNVs of MYH3 gene
      were significantly associated with growth traits of NY cattle, and the
      individuals with copy number gain showed better phenotypes than the loss and/or
      median groups (P<0.05). This study firstly attempted to establish the
      correlations between CNVs of candidate genes and growth traits, and our results
      suggested that the CNVs of MYH3 gene may be utilized as the potential markers for
      economic traits in selection breeding programs of Chinese cattle. 

PMID- 24316129
TI  - A unique case of a discontinuous duplication 3q26.1-3q28 resulting from a
      segregation error of a maternal complex chromosomal rearrangement involving an
      insertion and an inversion.
AB  - Until now, few cases of partial trisomy of 3q due to segregation error of
      parental balanced translocation and segregation of a duplicated deficient product
      resulting from parental pericentric inversion have been reported so far. Only
      five cases of chromosomal insertion malsegregation involving 3q region are
      available yet, thus making it relatively rare. In this case report, we are
      presenting a unique case of discontinuous partial trisomy of 3q26.1-q28 region
      which resulted from a segregation error of two insertions involving 3q26.1 to
      3q27.3 and 3q28 regions with ~21Mb and ~2Mb sizes, respectively. The maternally
      inherited insertion was cytogenetically characterized as der(8)(8pter->8p22::3q26
      >3q27.3::3q28->3q28::8p22->8qter) and the patient's major clinical features
      involved Dandy Walker malformation, sub-aortic ventricular septal defect,
      upslanting palpebral fissures, clinodactyly, hirsutism, and prominent forehead.
      Besides, a review of the literature involving cases with similar chromosomal
      imbalances and cases with "3q-duplication syndrome" is also provided.

PMID- 24316131
TI  - Evidence for field effect cancerization in colorectal cancer.
AB  - We compared transcript expression, and chromosomal changes on a series of tumors
      and surrounding tissues to determine if there is evidence of field cancerization
      in colorectal cancer. Epithelial cells were isolated from tumors and areas
      adjacent to the tumors ranging from 1 to 10cm. Tumor abnormalities mirrored those
      previously reported for colon cancer and while the number and size of the
      chromosomal abnormalities were greatly reduced in cells from surrounding regions,
      many chromosome abnormalities were discernable. Interestingly, these
      abnormalities were not consistent across the field in the same patient samples
      suggesting a field of chromosomal instability surrounding the tumor. A mutator
      phenotype has been proposed to account for this instability which states that the
      genotypes of cells within a tumor would not be identical, but would share at
      least a single mutation in any number of genes, or a selection of genes affecting
      a specific pathway which provide a proliferative advantage. 

PMID- 24316130
TI  - Recruitment and diversification of an ecdysozoan family of neuropeptide hormones
      for black widow spider venom expression.
AB  - Venoms have attracted enormous attention because of their potent physiological
      effects and dynamic evolution, including the convergent recruitment of homologous
      genes for venom expression. Here we provide novel evidence for the recruitment of
      genes from the Crustacean Hyperglycemic Hormone (CHH) and arthropod Ion Transport
      Peptide (ITP) superfamily for venom expression in black widow spiders. We
      characterized latrodectin peptides from venom gland cDNAs from the Western black
      widow spider (Latrodectus hesperus), the brown widow (Latrodectus geometricus)
      and cupboard spider (Steatoda grossa). Phylogenetic analyses of these sequences
      with homologs from other spider, scorpion and wasp venom cDNAs, as well as
      CHH/ITP neuropeptides, show latrodectins as derived members of the CHH/ITP
      superfamily. These analyses suggest that CHH/ITP homologs are more widespread in
      spider venoms, and were recruited for venom expression in two additional
      arthropod lineages. We also found that the latrodectin 2 gene and nearly all
      CHH/ITP genes include a phase 2 intron in the same position, supporting
      latrodectin's placement within the CHH/ITP superfamily. Evolutionary analyses of
      latrodectins suggest episodes of positive selection along some sequence lineages,
      and positive and purifying selection on specific codons, supporting its
      functional importance in widow venom. We consider how this improved understanding
      of latrodectin evolution informs functional hypotheses regarding its role in
      black widow venom as well as its potential convergent recruitment for venom
      expression across arthropods. 

PMID- 24316132
TI  - DuctApe: a suite for the analysis and correlation of genomic and OmniLogTM
      Phenotype Microarray data.
AB  - Addressing the functionality of genomes is one of the most important and
      challenging tasks of today's biology. In particular the ability to link genotypes
      to corresponding phenotypes is of interest in the reconstruction and
      biotechnological manipulation of metabolic pathways. Over the last years, the
      OmniLogTM Phenotype Microarray (PM) technology has been used to address many
      specific issues related to the metabolic functionality of microorganisms.
      However, computational tools that could directly link PM data with the gene(s) of
      interest followed by the extraction of information on gene-phenotype correlation
      are still missing. Here we present DuctApe, a suite that allows the analysis of
      both genomic sequences and PM data, to find metabolic differences among PM
      experiments and to correlate them with KEGG pathways and gene presence/absence
      patterns. As example, an application of the program to four bacterial datasets is
      presented. The source code and tutorials are available at
      http://combogenomics.github.io/DuctApe/. 

PMID- 24316133
TI  - Epigenetic regulation of microRNA-128a expression contributes to the apoptosis
      resistance of human T-cell leukaemia jurkat cells by modulating expression of fas
      associated protein with death domain (FADD).
AB  - Increased expression of miR-128a is often observed in acute lymphoblastic
      leukaemia (ALL) compared with its expression in acute myeloid leukaemia (AML).
      The objective of this study was to investigate the role of miR-128a, especially
      that in the Fas-signalling pathway, in T-cell leukaemia cells. The role of miR
      128a in Fas-mediated apoptosis was examined by using Fas-activating antibody (CH
      11)-susceptible Jurkat cells and -resistant Jurkat/R cells. Whereas ectopic
      expression of miR-128a conferred Fas-resistance on Jurkat cells by directly
      targeting Fas-associated protein with death domain (FADD), antagonizing miR-128a
      expression sensitized Jurkat/R cells to the Fas-mediated apoptosis through
      derepression of FADD expression. Myeloid leukaemia HL60 and K562 cells were also
      CH-11-resistant, sharing a similar resistant mechanism with Jurkat/R cells.
      Furthermore, CH-11 induced demethylation of the promoter region of miR-128a with
      resultant up-regulation of miR-128a expression in Jurkat/R cells, which was shown
      to be a mechanism for the resistance ofJurkat/R cells to Fas-mediated apoptosis.
      Our results indicate that the induction of miR-128a expression by DNA
      demethylation is a novel mechanism of resistance to Fas-mediated apoptosis.

PMID- 24316134
TI  - Ionizing radiation-inducible miR-494 promotes glioma cell invasion through EGFR
      stabilization by targeting p190B rhoGAP.
AB  - MicroRNAs (miRNAs) play an important role in various stages of tumor progression.
      miR-494, which we had previously identified as a miRNA induced by ionizing
      radiation (IR) in the glioma cell line U-251, was observed to enhance invasion of
      U-251 cells by activating MMP-2. The miR-494-induced invasive potential was
      accompanied by, and dependent on, epidermal growth factor receptor (EGFR)
      upregulation and the activation of its downstream signaling constituents, Akt and
      ERK. The upregulation of EGFR by miR-494 involved the suppression of lysosomal
      protein turnover. Among the putative target proteins tested, p190B RhoGAP (p190B)
      was downregulated by miR-494, and its reduced expression was responsible for the
      increase in EGFR expression. A reporter assay using a luciferase construct
      containing p190B 3'-untranslated region (3'UTR) confirmed that p190B is a direct
      target of miR-494. Downregulation of p190B by small interfering RNA (siRNA)
      transfection closely mimicked the outcomes of miR-494 transfection, and showed
      increased EGFR expression, MMP-2 secretion, and invasion. Ectopic expression of
      p190B suppressed the miR-494-induced EGFR upregulation and invasion promotion,
      thereby suggesting that p190B depletion is critical for the invasion-promoting
      action of miR-494. Collectively, our results suggest a novel function for miR-494
      and its potential application as a target to control invasiveness in cancer
      therapy.

PMID- 24316135
TI  - Caveolae-mediated endocytosis of the glucosaminoglycan-interacting adipokine
      tartrate resistant acid phosphatase 5a in adipocyte progenitor lineage cells.
AB  - Adipogenesis depends on growth factors controlling proliferation/differentiation
      of mesenchymal stem cells (MSCs). Membrane binding and endocytosis of growth
      factors are often coupled to receptor activation and downstream signaling leading
      to specific cellular responses. The novel adipokine tartrate-resistant acid
      phosphatase (TRAP) 5a exhibits a growth factor-like effect on MSCs and pre
      adipocytes and induces hyperplastic obesity in vivo. However its molecular
      interaction with pre-adipocytes remains unknown. Therefore, this study aimed to
      investigate membrane interaction of TRAP and its endocytosis routes in pre
      adipocytes. Confocal and/or electron microscopy were used to detect TRAP in
      untreated or TRAP 5a/b treated pre-adipocytes under conditions that allow or
      inhibit endocytosis in combination with co-staining of endocytotic vesicles. TRAP
      interaction with heparin/heparan sulfate was verified by gel filtration. It could
      be shown that TRAP 5a, but not 5b, binds to the membrane of pre-adipocytes where
      it co-localizes with heparin-sulfate proteoglycan glypican-4. Also in vitro, TRAP
      5a exhibited affinity for both heparin and heparan sulfate with heparin
      inhibiting its enzyme activity. Upon caveolae-mediated endocytosis of saturating
      levels of TRAP 5a, TRAP 5a co-localized intracellularly with glypican-4 and late
      endosomal marker Rab-7 positive vesicles. The protein was also located in
      multivesicular bodies (MVBs) but did not co-localize with lysosomal marker LAMP
      1. TRAP 5a endocytosis was also detectable in pre-osteoblasts, but not
      fibroblasts, embryonic MSCs or mature adipocytes. These results indicate that
      TRAP 5a exhibits binding to cell surface, endocytosis and affinity to
      glucosaminoglycans (GAGs) in pre-adipocyte and pre-osteoblast lineage cells in a
      manner similar to other heparin-binding growth factors.

PMID- 24316136
TI  - Analysis of alpha3 GlyR single particle tracking in the cell membrane.
AB  - Single particle tracking (SPT) of transmembrane receptors in the plasma membrane
      often reveals heterogeneous diffusion. A thorough interpretation of the
      displacements requires an extensive analysis suited for discrimination of
      different motion types present in the data. Here the diffusion pattern of the
      homomeric alpha3-containing glycine receptor (GlyR) is analyzed in the membrane
      of HEK 293 cells. More specifically, the influence of the alpha3 RNA splice
      variants alpha3K and alpha3L on lateral membrane diffusion of the receptor is
      revealed in detail. Using a combination of ensemble and local SPT analysis, free
      and anomalous diffusion parameters are determined. The GlyR alpha3 free diffusion
      coefficient is found to be 0.13 +/- 0.01 microm2/s and both receptor variants
      display confined motion. The confinement probability level and residence time are
      significantly elevated for the alpha3L variant compared to the alpha3K variant.
      Furthermore, for the alpha3L GlyR, the presence of directed motion was also
      established, with a velocity matching that of saltatory vesicular transport.
      These findings reveal that alpha3 GlyRs are prone to different types of anomalous
      diffusion and reinforce the role of RNA splicing in determining lateral membrane
      trafficking.

PMID- 24316137
TI  - Ultrasound-guided percutaneous microwave ablation for submucosal uterine
      fibroids.
AB  - STUDY OBJECTIVE: To prospectively evaluate the efficiency and safety of
      ultrasound-guided percutaneous microwave ablation (PMWA) in treating symptomatic
      submucosal uterine myomas. DESIGN: Self-controlled study (Canadian Task Force
      classification II-1). SETTING: Single center. PATIENTS: Twenty-two premenopausal
      women with 22 symptomatic submucosal uterine myomas. INTERVENTION: All patients
      underwent ultrasound-guided PMWA. MEASUREMENTS AND MAIN RESULTS: PMWA was
      performed in 22 premenopausal women with 22 symptomatic submucosal uterine
      myomas. Mean (SD) patient age was 42 (4.60) years (95% confidence interval [CI],
      39.96-44.04). Five symptomatic submucosal uterine myomas were identified as type
      0, 7 as type 1, and 10 as type 2. Contrast-enhanced ultrasound and magnetic
      resonance imaging were performed before and after surgery. Myoma volume,
      hemoglobin concentration, and scores on the UFS-QOL (Uterine Fibroid Symptom and
      Quality of Life) questionnaire were recorded before and at 3 and 12 months after
      ablation. Complications were also recorded. In all patients, therapy was
      completed with a single ablation. The baseline diameter of the symptomatic
      submucosal uterine myomas was 4.90 (1.60) cm. Mean myoma volume reduction rate
      was 81.46% (16.33%) (95% CI, 73.06%-89.86%) at 3 months (p < .001) and reached
      90.00% (9.79%) (95% CI, 85.07-95.13) at 12 months (p < .001). At 3 months after
      ablation, hemoglobin concentration increased from 88.64 (21.87) g/L (95% CI,
      78.94-98.34) to 123.21 (15.77) g/L (95% CI, 115.10-131.32) (p < .001), and
      remained stable at 12 months, with a value of 125.92 (14.90) g/L (95% CI, 117.98
      133.86). Scores on the UFS-QOL were comparable, with normal levels observed at 1
      year. No major complications were observed. Nine patients were discharged with
      necrotic masses. CONCLUSION: PMWA seems to be effective and safe for treatment of
      submucosal myomas.

PMID- 24316138
TI  - Imaging for uterine myomas and adenomyosis.
AB  - Uterine myomas and adenomyosis are common findings, in particular in patients
      with symptoms of abdominal enlargement, pelvic pressure, abnormal uterine
      bleeding, dysmenorrhea, and dyspareunia. Diagnosis and differentiation between
      the 2 entities are critical in establishing treatment options and the operative
      approach for surgical management. Herein are reviewed diagnostic options, their
      relative accuracy, and the effect of accurate diagnosis on treatment. A review
      was performed using PubMed, MdConsult, OVID, and reviews including cross
      referenced articles and prospective and retrospective studies published from 1980
      to 2013. Also reviewed are use of ultrasound with its various methods, magnetic
      resonance imaging, computed tomography, and positron emission tomography in the
      diagnosis, pretreatment evaluation, and differentiation of myomas and
      adenomyosis. 

PMID- 24316139
TI  - Histologic characteristics of vaginal cuff tissue from patients with vaginal cuff
      dehiscence.
AB  - STUDY OBJECTIVE: To describe the histologic characteristics of vaginal tissue in
      patients with vaginal cuff dehiscence (VCD) after robotic hysterectomy and to
      compare this group with patients without dehiscence. DESIGN: Retrospective
      analysis (Canadian Task Force classification II-3). SETTING: Academic center.
      PATIENTS: Seven patients with VCD and 6 patients without VCD. INTERVENTIONS:
      Vaginal cuff tissue was obtained from all patients and was stained using
      hematoxylin-eosin and evaluated for acute and chronic inflammation markers
      including neutrophils, lymphocytes, and plasma cells. Immunohistochemical
      staining was performed and evaluated using the semiquantitative method for
      collagen types I and III, smooth muscle actin, and SM22alpha (myofibroblast)
      content. Grading was performed by 4 blinded investigators. The Mann-Whitney test
      was used to evaluate the 2 groups, and correlation coefficients for interobserver
      variability. MEASUREMENTS AND MAIN RESULTS: The VCD group, compared with the non
      VCD group, demonstrated significantly greater numbers of neutrophils (1.71 vs
      1.0; p = .04), lymphocytes (2.85 vs 1.33; p = .002), and plasma cells (2.2 vs
      1.0; p = .001). There was no statistical difference between the groups in amounts
      of collagen I (1.71 vs 1.27; p = .09) and collagen III (1.66 vs 1.38; p = .37),
      smooth muscle actin (1.23 vs 1.33; p = .65), and SM22alpha (1.85 vs 1.27; p =
      .09). Interobserver variability was low (kappa = 0.86; p = .76). CONCLUSION:
      Compared with the control group, patients with VCD demonstrated significantly
      higher levels of acute and chronic inflammatory cells. This finding suggests that
      a prolonged inflammatory phase may be delaying normal progression to reparation
      in patients with dehiscence.

PMID- 24316140
TI  - Diagnostic performance of ultrasound for macroscopic hematuria in the era of
      multidetector computed tomography urography.
AB  - PURPOSE: The objective of this study was to evaluate the diagnostic performance
      of ultrasound for detecting urinary tract neoplasm in the setting of macroscopic
      hematuria by using multidetector computed tomography urography (MDCTU) and
      cystoscopy as the reference standard. METHODS: This retrospective study was
      approved by our institutional review board. Patients with macroscopic hematuria
      who were investigated with an abdominal or renal ultrasound, an MDCTU, and a
      cystoscopy between January 2007 and December 2009, were eligible (95 patients).
      Exclusion criteria were time interval >12 months between index and reference
      tests or the absence of histopathologic proof of malignancy. Ultrasound results
      of the remaining 86 patients were collected and compared with the reference
      standard test, which was the combination of MDCTU for the assessment of upper
      urinary tract and cystoscopy for assessment of the lower urinary tract. The final
      diagnosis of neoplasm was based on pathologic findings. RESULTS: Urinary tract
      neoplasm was diagnosed in 20% of the patients (17/86). Sensitivity, specificity,
      positive and negative predictive values, and positive and negative likelihood
      ratios of ultrasound for detecting urinary tract neoplasms were 35.3% (6/17),
      89.9% (62/69), 46.2% (6/13), 84.9% (62/73), 3.48 (95% confidence interval, 1.34
      9.02), and 0.72 (95% confidence interval, 0.5-1.3), respectively. CONCLUSION:
      Sensitivity of ultrasound for the evaluation of macroscopic hematuria in the era
      of MDCTU is lower than expected. Results of our study suggest that patients with
      macroscopic hematuria should undergo MDCTU as first-line imaging modality, with
      little added benefit from ultrasound.

PMID- 24316141
TI  - Study of the cytokine polymorphisms in correlation to rejection and graft
      survival in renal allograft donors and recipients from a homogenous Saudi
      population.
AB  - OBJECTIVES: Allograft outcome can be improved with the discovery of risk factors
      that influence adverse events and may allow individualization of patients'
      treatment. Rejection is the main hurdle to successful transplantation and the
      immune response is the key effecter to rejection development. Hence, the major
      objective of the present study was to assess the relationship between single
      nucleotide polymorphisms (SNPs) in 5 cytokine genes, HLA mismatch and graft
      outcome in a cohort of 100 Saudi kidney transplant recipients and 100 living
      related donors at a single transplant center. MATERIALS & METHODS: Genotyping of
      the following positions: TNFA (-308G/A), TGFB1 (codon 10T/C, codon 25C/G), IL-10
      (-1082G/A, -819C/T, -592C/A), IL-6 (-174C/G), and IFNG (+874T/A) were performed.
      RESULTS: The majority of the donors whose recipients presented with either
      cellular or antibody mediated graft rejection (90% and 100%) respectively were
      found to be significantly (p=0.0351) associated with intermediate or high IL-10
      producing haplotypes, compared to those with stable grafts (58.66%). Haplotypes
      linked with lower IL-10 production were not detected in the donors or their
      recipients with antibody mediated graft rejection compared to donors with stable
      graft (41.33%). The distribution of donor IL-10-1082 haplotypes (GG, GA, AA)
      showed a statistically significant association of IL-10-1082 GA genotype
      (p=0.0351) with rejection, when grouped according to patients' rejection status.
      No other statistically significant deviations were observed in the donors'
      genotypes. Analyses of cytokine polymorphisms in the recipients revealed no
      significant association. Multivariate logistic regression analyses showed that
      only HLA-DRB1 mismatch significantly influenced graft loss (p=0.0135).
      CONCLUSION: This study demonstrates that the donor IL-10 genotypes and HLA-DRB1
      mismatch are key determinants in graft outcome after renal transplantation.

PMID- 24316142
TI  - When the zebra loses its stripes but is still in the savannah: results from a
      semantic priming paradigm in semantic dementia.
AB  - Studies using semantic priming paradigms to measure the integrity of the features
      underlying concepts in semantic dementia (SD) reported differential impairment,
      in that functional features appeared to be more robust to brain damage than other
      features, such as perceptual ones. However, these prior studies were single case
      reports and the inclusion of too many heterogeneous features under the
      "functional features" heading casts doubts on their apparent preservation. To
      verify the robustness of functional features compared with perceptual ones, we
      carried out a group study where we deliberately restricted the exploration of
      semantic features to two clearly defined types of attribute: visuoperceptual
      ("visual") versus contextual-functional ("contextual"). We administered an
      implicit lexical-decision priming task to 8 SD patients and 31 healthy matched
      controls, at baseline. Four of the patients underwent a follow-up assessment at
      one year. For controls, we found a significant priming effect in the visual
      condition, but not in the contextual one, whereas the SD group exhibited the
      reverse pattern of performances. The follow-up data provided evidence of the
      robustness of the dissociation between priming performances in the two attribute
      conditions. The fact that a particular priming effect was observed in the SD
      patients but not in controls could be regarded as a sign of semantic
      disequilibrium. Since perceptual features have been shown to be a core
      determinant of similarity-based/taxonomic relationships, whereas complementary
      based/thematic processing relies mainly on contextual relationships, we
      interpreted our findings in terms of the differential recruitment of one of the
      two systems of semantic relationships (taxonomic vs. thematic). Moreover, these
      two distinct and parallel systems have previously been reported to coexist - and
      compete - in healthy adults. We thus argue that controls automatically drew on
      similarity-based/taxonomic relationships, leading to a significant priming effect
      for visual features but not for contextual ones. By contrast, their impaired
      perceptual features forced the SD patients to resort to the system of thematic
      relationships. 

PMID- 24316143
TI  - Resistance exercise acutely enhances mesenteric artery insulin-induced relaxation
      in healthy rats.
AB  - AIMS: We evaluated the mechanisms involved in insulin-induced vasodilatation
      after acute resistance exercise in healthy rats. MAIN METHODS: Wistar rats were
      divided into 3 groups: control (CT), electrically stimulated (ES) and resistance
      exercise (RE). Immediately after acute RE (15 sets with 10 repetitions at 70% of
      maximal intensity), the animals were sacrificed and rings of mesenteric artery
      were mounted in an isometric system. After this, concentration-response curves to
      insulin were performed in control condition and in the presence of LY294002 (PI3K
      inhibitor), L-NAME (NOS inhibitor), L-NAME+TEA (K(+) channels inhibitor),
      LY294002+BQ123 (ET-A antagonist) or ouabain (Na(+)/K(+) ATPase inhibitor). KEY
      FINDINGS: Acute RE increased insulin-induced vasorelaxation as compared to
      control (CT: Rmax=7.3 +/- 0.4% and RE: Rmax=15.8 +/- 0.8%; p<0.001). NOS
      inhibition reduced (p<0.001) this vasorelaxation from both groups (CT: Rmax=2.0
      +/- 0.3%, and RE: Rmax=-1.2 +/- 0.1%), while PI3K inhibition abolished the
      vasorelaxation in CT (Rmax=-0.1+/-0.3%, p<0.001), and caused vasoconstriction in
      RE (Rmax=-6.5 +/- 0.6%). That insulin-induced vasoconstriction on PI3K inhibition
      was abolished (p<0.001) by the ET-A antagonist (Rmax=2.9 +/- 0.4%). Additionally,
      acute RE enhanced (p<0.001) the functional activity of the ouabain-sensitive
      Na(+)/K(+) ATPase activity (Rmax=10.7 +/- 0.4%) and of the K(+) channels (Rmax=
      6.1+/-0.5%; p<0.001) in the insulin-induced vasorelaxation as compared to CT.
      SIGNIFICANCE: Such results suggest that acute RE promotes enhanced insulin
      induced vasodilatation, which could act as a fine tuning to vascular tone.

PMID- 24316144
TI  - Predetermination of sexual fate in a turtle with temperature-dependent sex
      determination.
AB  - Egg incubation temperature determines offspring sex in many reptilian species,
      including red-eared slider turtles, where embryos incubated at low temperatures
      during the initial stages of gonad formation develop as males, while those kept
      at higher temperatures develop as females. Incubation at the threshold, or
      pivotal, temperature (PvT) yields an even ratio of males and females. This strong
      susceptibility to temperature indicates that each embryo of this species is
      competent to develop as a male or a female. However, the mechanism that
      determines sexual fate at the PvT has not been identified. One possibility is
      that sexual fate is stochastic at the PvT, but coordinated by systemic signals
      within a single embryo. If this is the case, gonads explanted separately to
      culture should not coordinate their fate. Here we show that gonad pairs from
      embryos incubated at the PvT share a strong predisposition for one sex or the
      other when cultured in isolation, indicating that they were affected by shared
      genetic signals, maternally-deposited yolk hormones or other transient influences
      received prior to the stage of dissection. In ovo studies involving shifts from
      the male- or female-producing temperature to the PvT further indicate that
      embryos adopt a sexual differentiation trajectory many days prior to the onset of
      morphological differentiation into testes or ovaries and usually maintain this
      fate in the absence of an extreme temperature signal favoring the development of
      the other sex. Our findings therefore suggest that the outcome of sex
      determination in these reptiles is heavily influenced (i) by an inherent
      predisposition at the PvT and (ii) by the sexual differentiation trajectory
      established early in gonad development under male- or female-producing
      temperatures. 

PMID- 24316145
TI  - Co-existence of photosynthetic and respiratory activities in cyanobacterial
      thylakoid membranes.
AB  - The thylakoid membranes of cyanobacteria are the major sites of respiratory
      electron transport as well as photosynthetic light reactions. The photosynthetic
      and respiratory electron transport chains share some components, and their
      presence in the same membrane opens up the possibility for a variety of
      "unorthodox" electron transport routes. Many of the theoretically possible
      electron transport pathways have indeed been detected in particular species and
      circumstances. Electron transport has a crucial impact on the redox balance of
      the cell and therefore the pathways of electron flow in the cyanobacterial
      thylakoid membrane must be tightly regulated. This review summarises what is
      known of cyanobacterial electron transport components, their interactions and
      their sub-cellular location. The role of thylakoid membrane organisation in
      controlling electron transport pathways is discussed with respect to recent
      evidence that the larger-scale distribution of complexes in the membrane is
      important for controlling electron exchange between the photosynthetic and
      respiratory complexes. The distribution of complexes on scales of 100nm or more
      is under physiological control, showing that larger-scale thylakoid membrane re
      arrangement is a key factor in controlling the crosstalk between photosynthetic
      and respiratory electron transport. This article is part of a Special Issue
      entitled: Dynamic and ultrastructure of bioenergetic membranes and their
      components.

PMID- 24316146
TI  - Structural and kinetic properties of Rhodobacter sphaeroides photosynthetic
      reaction centers containing exclusively Zn-coordinated bacteriochlorophyll as
      bacteriochlorin cofactors.
AB  - The Zn-BChl-containing reaction center (RC) produced in a bchD (magnesium
      chelatase) mutant of Rhodobacter sphaeroides assembles with six Zn
      bacteriochlorophylls (Zn-BChls) in place of four Mg-containing
      bacteriochlorophylls (BChls) and two bacteriopheophytins (BPhes). This protein
      presents unique opportunities for studying biological electron transfer, as Zn
      containing chlorins can exist in 4-, 5-, and (theoretically) 6-coordinate states
      within the RC. In this paper, the electron transfer perturbations attributed
      exclusively to coordination state effects are separated from those attributed to
      the presence, absence, or type of metal in the bacteriochlorin at the HA pocket
      of the RC. The presence of a 4-coordinate Zn(2+) ion in the HA bacteriochlorin
      instead of BPhe results in a small decrease in the rates of the P*->P(+)HA(-)
      >P(+)QA(-) electron transfer, and the charge separation yield is not greatly
      perturbed; however coordination of the Zn(2+) by a fifth ligand provided by a
      histidine residue results in a larger rate decrease and yield loss. We also
      report the first crystal structure of a Zn-BChl-containing RC, confirming that
      the HA Zn-BChl was either 4- or 5-coordinate in the two types of Zn-BChl
      containing RCs studied here. Interestingly, a large degree of disorder, in
      combination with a relatively weak anomalous difference electron density was
      found in the HB pocket. These data, in combination with spectroscopic results,
      indicate partial occupancy of this binding pocket. These findings provide
      insights into the use of BPhe as the bacteriochlorin pigment of choice at HA in
      both BChl- and Zn-BChl-containing RCs found in nature. 

PMID- 24316148
TI  - ELABELA: a hormone essential for heart development signals via the apelin
      receptor.
AB  - We report here the discovery and characterization of a gene, ELABELA (ELA),
      encoding a conserved hormone of 32 amino acids. Present in human embryonic stem
      cells, ELA is expressed at the onset of zebrafish zygotic transcription and is
      ubiquitous in the naive ectodermal cells of the embryo. Using zinc-finger
      nuclease-mediated gene inactivation in zebrafish, we created an allelic series of
      ela mutants. ela null embryos have impaired endoderm differentiation potential
      marked by reduced gata5 and sox17 expression. Loss of Ela causes embryos to
      develop with a rudimentary heart or no heart at all, surprisingly phenocopying
      the loss of the apelin receptor (aplnr), which we show serves as Ela's cognate G
      protein-coupled receptor. Our results reveal the existence of a peptide hormone,
      ELA, which, together with APLNR, forms an essential signaling axis for early
      cardiovascular development. 

PMID- 24316147
TI  - The plasma membrane flattens out to fuel cell-surface growth during Drosophila
      cellularization.
AB  - Cell-shape change demands cell-surface growth, but how growth is fueled and
      choreographed is still debated. Here we use cellularization, the first complete
      cytokinetic event in Drosophila embryos, to show that cleavage furrow ingression
      is kinetically coupled to the loss of surface microvilli. We modulate furrow
      kinetics with RNAi against the Rho1-GTPase regulator slam and show that furrow
      ingression controls the rate of microvillar depletion. Finally, we directly track
      the microvillar membrane and see it move along the cell surface and into
      ingressing furrows, independent of endocytosis. Together, our results demonstrate
      that the kinetics of the ingressing furrow regulate the utilization of a
      microvillar membrane reservoir. Because membranes of the furrow and microvilli
      are contiguous, we suggest that ingression drives unfolding of the microvilli and
      incorporation of microvillar membrane into the furrow. We conclude that plasma
      membrane folding/unfolding can contribute to the cell-shape changes that promote
      embryonic morphogenesis. 

PMID- 24316149
TI  - Responses of hepatic metallothioneins and apoptotic activity in Carassius auratus
      gibelio witness a release of cobalt and zinc from waterborne nanoscale
      composites.
AB  - The main goal of this study was to evaluate the ability of fish Carassius auratus
      tissues to release cobalt (Co) and zinc (Zn) cations present in the applied Co-
      and Zn-containing nanoscale composites (NCs). Male fish was subjected to 14day
      long action of Co- and Zn-NCs, as well as of Co(2+) and Zn(2+) or polymeric
      substance (PS) used for the NC preparation and derived from the vinylpyrrolidone.
      50MUg?L(-1) of Co and 100MUg?L(-1) of Zn were applied either as a salt or a
      nanocomposite. Both Co and Co-NC increased (3.1 and 2.3 times, respectively)
      concentration of total Co, metallothionein-related Co (3.7 and 6.6 times,
      respectively) and thiols (by 71 and 95%, respectively), and caspase-3 activity
      (2.2 and 3.7 times, respectively) in the fish liver. At the same time, Co and Co
      NC decreased glutathione level (1.8 and 1.9 times, respectively) and activated
      vitellogenesis (5.1 and 9.9 times, respectively) in the fish liver. Both Zn and
      Zn-NC increased markedly concentrations of metallothionein-related Zn (2.4 and
      2.9 times, respectively) and Cu (2.8 and 3.2 times, respectively), and decreased
      metallothionein-related thiol (2.5 and 4.2 times, respectively), oxyradical (by
      30.4 and 44.2%, respectively), and caspase-3 (3.0 and 5.3 times, respectively)
      levels in the fish liver. These peculiarities are common for metal and metal-NC
      and witness a release of metal from NS in fish organism. The differences in the
      levels of DNA strand breaks, biotransformation enzymes and total Zn levels in the
      liver were dependent on the kind of exposure. 

PMID- 24316151
TI  - The role of trait impulsivity in response inhibition: event-related potentials in
      a stop-signal task.
AB  - The study examined the relation between self-reported impulsivity and inhibitory
      control in normal individuals. We compared stopping performance and neural
      correlates of stopping on stop-signal task between participants who scored in the
      top (n=12) and bottom 25% (n=12) on Impulsivity Scale from a sample of 305 male
      adults. Participants scoring high on impulsivity did not show impaired inhibitory
      control. However, it seems that the high impulsive tended to make more errors of
      commission and omission. Enhanced N1 amplitudes were found in successful than
      failed inhibition trials. The high impulsive group had smaller P3 amplitude than
      the low impulsive group. It appears that the high impulsive group may have a less
      efficient inhibitory control. Impulsivity Scale non-planning impulsiveness score
      and inattention score of Adult ADHD Self-Report Scale (ASRS) were negatively
      correlated with P3 amplitudes on successful inhibition trails, suggesting that
      impulsivity could have the potential influence on inhibitory control. 

PMID- 24316150
TI  - Involvement of CTR1 and ATP7A in lead (Pb)-induced copper (Cu) accumulation in
      choroidal epithelial cells.
AB  - The blood-cerebrospinal fluid barrier (BCB) plays a key role in maintaining
      copper (Cu) homeostasis in the brain. Cumulative evidences indicate that lead
      (Pb) exposure alters cerebral Cu homeostasis, which may underlie the development
      of neurodegenerative diseases. This study investigated the roles of Cu
      transporter 1 (CTR1) and ATP7A, two Cu transporters, in Pb-induced Cu
      accumulation in the choroidal epithelial cells. Pb exposure resulted in increased
      intracellular (64)Cu retention, accompanying with up-regulated CTR1 level.
      Knockdown of CTR1 using siRNA before Pb exposure diminished the Pb-induced
      increase of (64)Cu uptake. The expression level of ATP7A was down-regulated
      following the Pb exposure. ATP7A siRNA knockdown, or PCMB treatment, inhibited
      the (64)Cu efflux from the cells, while the following additional incubation with
      Pb failed to further increase the intracellular (64)Cu retention. Cu exposure, or
      intracellular Cu accumulation following the tetracycline (Tet)-induced
      overexpression of CTR1, did not result in significant change in ATP7A expression.
      Taken together, these data indicate that CTR1 and ATP7A play important roles in
      Cu transport in choroidal epithelial cells, and the Pb-induced intracellular Cu
      accumulation appears to be mediated, at least in part, via the alteration of CTR1
      and ATP7A expression levels following Pb exposure. 

PMID- 24316152
TI  - Incremental effect from integrating 3D-mammography (tomosynthesis) with 2D
      mammography: Increased breast cancer detection evident for screening centres in a
      population-based trial.
AB  - BACKGROUND & OBJECTIVES: Three-dimensional (3D)-mammography (tomosynthesis) may
      improve breast cancer detection. We examined centre-specific effect of integrated
      2D/3D mammography based on the STORM (screening with tomosynthesis or standard
      mammography) trial. METHODS: Asymptomatic women who attended population-based
      screening through Trento and Verona screening centres were recruited into STORM,
      a prospective comparison of screen-reading in two sequential phases: 2D
      mammography only and integrated 2D/3D mammography. Outcomes were the number and
      rates of detected cancers and of false positive recalls (FPR), and incremental
      cancer detection rate (CDR). Paired binary data were compared using Mc Nemar's
      test. RESULTS: Of 33 cancers detected in Trento, 21 were detected at both 2D and
      2D/3D screening, 12 cancers were detected only with integrated 2D/3D screening
      compared with none detected at 2D-only screening (P < 0.001). Of the 26 cancers
      detected in Verona, 18 were detected at both 2D and 2D/3D screening, 8 cancers
      were detected only with integrated 2D/3D screening compared with none detected at
      2D-only screening (P = 0.008). There were no differences between centres in
      baseline CDR, and incremental CDR attributable to 3D-mammography was similar for
      Trento (2.8/1000 screens) and for Verona (2.6/1000 screens). Trento had 239 FPR
      (5.7% of screens): 103 FPR at both screen-readings, 93 FPR only at 2D-mammography
      compared with 43 FPR only at 2D/3D-mammography (p < 0.001). Verona had 156 FPR
      (5.2% of screens): 78 FPR at both screen-readings, 48 FPR only at 2D-mammography
      compared with 30 FPR only at 2D/3D-mammography (p = 0.054). Estimated reduction
      in FPR proportion had recall been conditional to 2D/3D-mammography-positivity
      differed between centres (21.0% versus 11.5%; P = 0.02). CONCLUSION: Integrated
      2D/3D-mammography significantly increased cancer detection for both screening
      services; potential reduction in FPR is likely to differ between centres with
      those experiencing relatively higher FPR most likely to benefit from 2D/3D
      mammography screening.

PMID- 24316153
TI  - Canine borreliosis: are we facing the facts?

PMID- 24316154
TI  - Feasibility and repeatability of thermal quantitative sensory testing in normal
      dogs and dogs with hind limb osteoarthritis-associated pain.
AB  - The objectives of this study were to determine whether thermal quantitative
      sensory testing (QST) can be performed in client-owned dogs, is repeatable and
      whether QST differs between normal dogs and dogs with hind limb osteoarthritis
      (OA). This clinical, prospective, observational study used clinically normal dogs
      (n=23) and dogs with OA-associated hind limb pain (n=9). Thermal QST was
      performed in standing dogs using a high-powered light source delivered by a
      previously validated system. Dogs were tested on two occasions, 2 weeks apart.
      Five tests were performed on each hind limb at each time point. Repeated measures
      analysis of variance was used to evaluate the effects of leg, time point and
      OA/normal status on thermal threshold latencies (TTL). Additionally, paired t
      tests were used to compare the TTL of left and right limbs within groups and
      between time points. Thermal thresholds were successfully measured in 32 client
      owned dogs without prior training. TTL were significantly different between
      normal and OA dogs (P=0.012). There was no difference between limbs (P=0.744) or
      time periods (P=0.572), when analyzed by repeated measures analysis of variance,
      and no interactions between group and limb, visit and limb, or visit and group.
      In conclusion, thermal thresholds can be measured in client owned dogs with no
      prior training and are repeatable from week to week. Further data are required to
      determine if OA results in thermal hypoalgesia as measured at the distal hind
      limb and whether this is an indication of central sensitization.

PMID- 24316155
TI  - ORF5-based evolutionary and epidemiological dynamics of the type 1 porcine
      reproductive and respiratory syndrome virus circulating in Korea.
AB  - This study applied a number of advanced genetic analysis tools to investigate the
      evolutionary trajectories and epidemiological dynamics of Korean type 1 PRRSV
      based on variations in the ORF5 gene over a long-term period from 2005 to 2013.
      Maximum likelihood phylogenetic analysis performed on large, worldwide ORF5
      sequences (n=1127) strongly suggested no further introduction of genetically
      novel type 1 PRRSV into Korean pig farms, with the identification of only two
      clusters (I and II) in circulation to date. Using a codon-based extension of the
      Bayesian relaxed clock model, this study was able to distinguish between
      synonymous and non-synonymous substitutions and demonstrated that, while the
      absolute rates of synonymous substitution (E[S]) were similar between clusters I
      and II, the absolute rate of non-synonymous substitution (E[N]) was significantly
      different between the clusters. Cluster I was found to have an elevated E[N]/E[S]
      ratio relative to cluster II on the internal branches, compared to the external
      branches. Additionally, many fewer sites were predicted under diversifying
      selection in cluster II than in cluster I. Utilizing the Bayesian skyride method
      and the novel Bayesian birth-death skyline plot method, this study provided
      insights into the epidemiological dynamics of type 1 PRRSV in Korea by revealing
      that each cluster experienced a unique epidemic growth and by uncovering
      correlations between the effective population size and effective reproductive
      number. 

PMID- 24316156
TI  - The complete mitochondrial genome of Toxascaris leonina: Comparison with other
      closely related species and phylogenetic implications.
AB  - Adults of Toxascaris leonina (Nematoda: Ascarididae) live in the gastrointestinal
      tract of both dogs and cats, and cause significant economic losses and potential
      public health problem worldwide. Although many studies have given insights into
      this significant pathogen, to date, the complete mitochondrial (mt) genome
      sequence is still not available for T. leonina. Here, we sequenced the complete
      mt genome of T. leonina. This AT-rich (71.53%) mt genome (14,310bp) is circular
      and consists of 36 genes, including 12 genes for proteins, 2 genes for rRNA and
      22 genes for tRNA. All mt genes of T. leonina are transcribed in the same
      direction. The gene order is the same as those of Ascaris spp. (Ascarididae),
      Toxocara spp. (Toxocaridae), Anisakis simplex and Contracaecum rudolphii B
      (Anisakidae), but distinct from that of Ascaridia spp. (Ascaridiidae).
      Phylogenetic analyses using concatenated amino acid sequences of 12 protein
      coding genes by Bayesian inference (BI) showed distinct groups with high
      statistical support, and our data confirm that T. leonina is a member of the
      Ascarididae, and that this family is more closely related to the Toxocaridae
      rather than the Anisakidae within the Ascaridoidea. The determination of mt
      genome sequences of T. leonina provides novel genetic markers for studies into
      the systematics, population genetics and epidemiology of this parasite. 

PMID- 24316157
TI  - A role for the ciliary marginal zone in the melanopsin-dependent intrinsic
      pupillary light reflex.
AB  - Maintenance of pupillary constriction in light-adapted rodents has traditionally
      been thought to involve a reflex between retina, brain and iris, with recent work
      identifying the melanopsin-expressing intrinsically photosensitive retinal
      ganglion cells (ipRGCs) as the major conduits for retinal input to the brain.
      There is also a less well-understood phenomenon whereby the iris of some mammals,
      including mice, will constrict to light when either the eye, or the iris itself
      is physically isolated from the brain. The intrinsic pupillary light reflex
      (iPLR) is the term given to pupil constriction in the absence of retinal input to
      the brain. Here, using an intraocular axotomy approach, we show that the iPLR in
      conscious mice spans a dynamic range over 3 log units of irradiance. This iPLR
      response is absent in melanopsin knockout (MKO) mice and can be significantly
      inhibited by atropine. Immunohistochemistry for cfos and melanopsin, in
      combination with light exposure revealed a population of small ipRGCs in the
      retinal ciliary marginal zone (CMZ), which remain responsive to light in
      axotomised mice. We report that damage to the CMZ in a novel in vitro preparation
      removes a significant component of the iPLR response, while a detailed
      immunohistochemical analysis of the CMZ in wildtype mice revealed a melanopsin
      rich plexus, which was consistently most intense in nasal retina. There were
      clear examples of melanopsin-positive, direct retino-ciliary projections, which
      appear to emanate from Brn3b negative, M1 type ipRGCs. These cells are clustered
      along the melanopsin-rich plexus nasally and may channel ipRGC signals from
      retina into the iris via ciliary body. Comparison between wildtype and MKO mice
      reveals that the ciliary body is also weakly stained for melanopsin. Our results
      show that the full extent of iPLR in mice requires cholinergic neurotransmission
      and intact signalling at the CMZ/ciliary body. This response may be mediated to
      some extent by ipRGCs, which send direct projections from the retina into ciliary
      body. In addition to the melanopsin-mediated iris sphincter constriction
      suggested by others, we propose a new mechanism, which may involve constriction
      of the ciliary body and ipRGC-mediated relaxation of the iris dilator muscle. 

PMID- 24316158
TI  - Focal damage to macaque photoreceptors produces persistent visual loss.
AB  - Insertion of light-gated channels into inner retina neurons restores neural light
      responses, light evoked potentials, visual optomotor responses and visually
      guided maze behavior in mice blinded by retinal degeneration. This method of
      vision restoration bypasses damaged outer retina, providing stimulation directly
      to retinal ganglion cells in inner retina. The approach is similar to that of
      electronic visual protheses, but may offer some advantages, such as avoidance of
      complex surgery and direct targeting of many thousands of neurons. However, the
      promise of this technique for restoring human vision remains uncertain because
      rodent animal models, in which it has been largely developed, are not ideal for
      evaluating visual perception. On the other hand, psychophysical vision studies in
      macaque can be used to evaluate different approaches to vision restoration in
      humans. Furthermore, it has not been possible to test vision restoration in
      macaques, the optimal model for human-like vision, because there has been no
      macaque model of outer retina degeneration. In this study, we describe
      development of a macaque model of photoreceptor degeneration that can in future
      studies be used to test restoration of perception by visual prostheses. Our
      results show that perceptual deficits caused by focal light damage are restricted
      to locations at which photoreceptors are damaged, that optical coherence
      tomography (OCT) can be used to track such lesions, and that adaptive optics
      retinal imaging, which we recently used for in vivo recording of ganglion cell
      function, can be used in future studies to examine these lesions. 

PMID- 24316159
TI  - All-trans retinoic acid prevents epidural fibrosis through NF-kappaB signaling
      pathway in post-laminectomy rats.
AB  - Laminectomy is a widely accepted treatment for lumbar disorders, and epidural
      fibrosis (EF) is a common complication. EF is thought to cause post-operative
      pain recurrence after laminectomy or discectomy. All-trans retinoic acid (ATRA)
      has shown anti-fibrotic, anti-inflammatory, and anti-proliferative functions. The
      object of this study was to investigate the effects of ATRA on the prevention of
      EF in post-laminectomy rats. In vitro, the anti-fibrotic effect of ATRA was
      demonstrated with cultured fibroblasts count, which comprised of those that were
      cultured with/without ATRA. In vivo, rats underwent laminectomy at the L1-L2
      levels. We first demonstrated the beneficial effects using 0.05% ATRA compared to
      vehicle (control group). We found that a higher concentration of ATRA (0.1%)
      achieved dose-dependent results. Hydroxyproline content, Rydell score, vimentin
      positive cell density, fibroblast density, inflammatory cell density and
      inflammatory factor expression levels all suggested better outcomes in the 0.1%
      ATRA rats compared to the other three groups. Presumably, these effects involved
      ATRA's ability to suppress transforming growth factor (TGF-beta1) and interleukin
      (IL)-6 which was confirmed with reverse-transcriptase polymerase chain reaction
      (RT-PCR). Finally we demonstrated that ATRA down-regulated nuclear factor (NF)
      kappaB by immunohistochemistry and western blotting for p65 and inhibition of
      kappaB (IkappaBalpha), respectively. Our findings indicate that topical
      application of ATRA can inhibit fibroblast proliferation, decrease TGF-beta1 and
      IL-6 expression level, and prevent epidural scar adhesion in rats. The highest
      concentration employed in this study (0.1%) was the most effective. ATRA
      suppressed EF through down-regulating NF-kappaB signaling, whose specific
      mechanism is suppression of IkappaB phosphorylation and proteolytic degradation. 

PMID- 24316161
TI  - Fluoxetine inhibits transient global ischemia-induced hippocampal neuronal death
      and memory impairment by preventing blood-brain barrier disruption.
AB  - Ischemia induces blood-brain barrier (BBB) disruption by matrix metalloproteases
      (MMPs) activation, leading to neuronal cell death. Here, we show that fluoxetine
      inhibits apoptotic cell death of hippocampal neuron and memory impairment by
      blocking BBB disruption after transient global ischemia. Fluoxetine treatment (10
      mg/kg) after global ischemia significantly inhibited mRNA expression of MMP-2 and
      -9 and reduced MMP-9 activity. By Evan blue assay, fluoxetine reduced ischemia
      induced BBB permeability. In parallel, fluoxetine significantly attenuated the
      loss of occludin and laminin in the hippocampal area after ischemia. By
      immunostaining with occludin antibody, fluoxetine preserved the integrity of
      vascular networks, especially in hippocampal areas after injury. Fluoxetine also
      prevented the infiltration of macrophages and inhibited the mRNA expression of
      inflammatory mediators after injury. In addition, the activation of microglia and
      astrocyte in hippocampal regions was significantly attenuated by fluoxetine.
      Finally, fluoxetine reduced apoptotic cell death of hippocampal neurons as well
      as vascular endothelial cell death and improved learning and memory. Thus, our
      study suggests that the neuroprotective effect of fluoxetine is likely mediated
      by blocking MMP activation followed BBB disruption after transient global
      ischemia, and the drug may represent a potential therapeutic agent for preserving
      BBB integrity following ischemic brain injury in humans. 

PMID- 24316162
TI  - Protein-binding properties of a designed steroidal lactam compound.
AB  - Introducing amide bonds into a steroid nucleus or its side chain may reduce the
      acute toxicity and enhance the pharmaceutical activity. In this work, a designed
      steroidal amide compound, named 3beta-hydroxy-17-aza-d-homo-5-androsten-17-one
      (HAAO), was synthesized and identified. The interactions between HAAO and human
      serum albumin (HSA) were studied by multiple spectroscopic methods and molecular
      modeling procedures. It was found that HAAO locates in Sudlow's site I in
      subdomain IIA of HSA molecules, relying on hydrogen bonds and van der Waals power
      to form HAAO-HSA complexes at ground state. The number of binding sites, binding
      constants, enthalpy change (DeltaH(theta)), Gibbs free energy change
      (DeltaG(theta)) and entropy change (DeltaS(theta)) were calculated at different
      temperatures based on fluorescence quenching theory and classical thermodynamic
      equation. The percentages content of the HSA's secondary structures in presence
      of HAAO were detected by circular dichroism (CD) spectra and compared with those
      in no presence of HAAO. In addition, the experimental results of both binding
      site and conformational change were further confirmed by molecular modeling
      investigation, in which more details of the binding were visually unfolded. The
      information provided by the study may be useful for designing novel
      chemotherapeutic drugs and be helpful both in the early stages of drug discovery
      and in clinical practice. 

PMID- 24316160
TI  - Repeated intermittent alcohol exposure during the third trimester-equivalent
      increases expression of the GABA(A) receptor delta subunit in cerebellar granule
      neurons and delays motor development in rats.
AB  - Exposure to ethanol (EtOH) during fetal development can lead to long-lasting
      alterations, including deficits in fine motor skills and motor learning. Studies
      suggest that these are, in part, a consequence of cerebellar damage. Cerebellar
      granule neurons (CGNs) are the gateway of information into the cerebellar cortex.
      Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition
      from Golgi cell interneurons; however, the effect of EtOH exposure on the
      development of GABAergic transmission in immature CGNs has not been investigated.
      To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy,
      neonatal pups were exposed intermittently to high levels of vaporized EtOH from
      postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH
      concentrations (SECs) to ~60 mM (~0.28 g/dl) during the 4 h of exposure. EtOH
      levels gradually decreased to baseline 8 h after the end of exposure.
      Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not
      significantly affected by postnatal alcohol exposure (PAE). However, PAE
      increased delta subunit expression at P28 as detected by immunohistochemical and
      western blot analyses. Also, electrophysiological studies with an agonist that is
      highly selective for delta-containing GABA(A) receptors, 4,5,6,7
      tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP
      induced tonic current. Behavioral studies of PAE rats did not reveal any deficits
      in motor coordination, except for a delay in the acquisition of the mid-air
      righting reflex that was apparent at P15 to P18. These findings demonstrate that
      repeated intermittent exposure to high levels of EtOH during the equivalent of
      the last trimester of human pregnancy has significant but relatively subtle
      effects on motor coordination and GABAergic transmission in CGNs in rats.

PMID- 24316163
TI  - Solid-state NMR study of fluorinated steroids.
AB  - Solid-state {(1)H}(13)C cross-polarization/magic angle spinning (CP/MAS) NMR
      spectroscopy was performed to analyze two fluorinated steroids, i.e.,
      betamethasone (BMS) and fludrocortisone acetate (FCA), that have fluorine
      attached to C9, as well as two non-fluorinated analogs, i.e., prednisolone (PRD)
      and hydrocortisone 21-acetate (HCA). The (13)C signals of BMS revealed multiplet
      patterns with splittings of 16-215Hz, indicating multiple ring conformations,
      whereas the (13)C signals of FCA, HCA, and PRD exhibited only singlet patterns,
      implying a unique conformation. In addition, BMS and FCA exhibited substantial
      deviation (>3.5ppm) in approximately half of the (13)C signals and significant
      deviation (>45ppm) in the (13)C9 signal compared to PRD and HCA, respectively. In
      this study, we demonstrate that fluorinated steroids, such as BMS and FCA, have
      steroidal ring conformation(s) that are distinct from non-fluorinated analogs,
      such as PRD and HCA. 

PMID- 24316164
TI  - Click chemistry inspired highly facile synthesis of triazolyl ethisterone
      glycoconjugates.
AB  - Numerous deoxy-azido sugars 3 were prepared by the reaction of tosyl/bromo sugars
      with NaN3 in dry DMF under heating condition. The 1,3-dipolar cycloaddition of
      deoxy-azido sugars 3 with ethisterone 4 to afford regioselective triazole-linked
      ethisterone glycoconjugates 5 was investigated in the presence of CuI and DIPEA
      in dichloromethane or CuSO4.5H2O and sodium ascorbate in aqueous medium. All the
      developed compounds were characterized by spectroscopic analysis (IR, (1)H &(13)C
      NMR, and MS spectra). Structure of triazolyl ethisterone glycoconjugate 5a has
      been further confirmed by its Single Crystal X-ray analysis. 

PMID- 24316166
TI  - Epiploic bypass flap: a new method of limb salvage. Anatomic basis and clinical
      application.
AB  - BACKGROUND: The incidence of critical limb ischemia increases with the aging of
      the population. Two-thirds of patients with critical limb ischemia present with
      trophic disorders. Revascularization decreases the rate of amputation. Infected
      wounds with exposure of the tendons, bones, or points of articulation cannot heal
      in spite of bridging and local debridement. Surgery associated with a distal
      venous bypass or recanalization and a free flap makes it possible to cover major
      tissue loss and offers a hemodynamic advantage by increasing the flow of the
      bypass, thanks to the vascular bed added by the flap. It is a complex surgery
      because of the multiplicity of anastomoses on the same arterial axis, with a risk
      of thrombosis and complications related to the venous autograft. To mitigate
      these disadvantages, we propose a new surgical method based on the use of a
      single anatomic unit, the epiploic bypass flap (BF), based on the gastroepiploic
      artery (GEA) as the inflow for a bypass and a free flap. The objective of this
      work was to analyze the anatomic feasibility of an epiploic BF and to determine
      its limits. METHODS: One hundred anatomic preparations were conducted with a
      measure of the internal and external diameters and the lengths of GEA and its
      branches and a radiograph after injection of a radiopaque product. A first
      clinical application was carried out. RESULTS: According to the data, our study
      confirms the anatomic feasibility of a BF. The average available length of GEA is
      245 mm (range: 210-280 mm). The average proximal diameter is 3 mm, and the distal
      diameter is 1.5 mm. The most distal epiploic branch that feeds the bypass is
      approximately 180 mm (range: 161-195 mm) of the origin of the GEA. The anatomic
      unit based on the GEA provides an arterial graft that is relatively long and a
      large flap that is both malleable and resistant to infection. CONCLUSIONS:
      Epiploic BF is a surgical technique that allows for distal revascularization and
      a simultaneous cover of the limb extremity. This technique can be useful in
      patients requiring a distal revascularization associated with a cutaneous cover.

PMID- 24316165
TI  - Treadmill exercise reverses dendritic spine loss in direct and indirect striatal
      medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      mouse model of Parkinson's disease.
AB  - Exercise has been shown to be beneficial for Parkinson's disease (PD). A major
      interest in our lab has been to investigate how exercise modulates basal ganglia
      function and modifies disease progression. Dopamine (DA) depletion leads to loss
      of dendritic spines within the caudate nucleus and putamen (striatum) in PD and
      its animal models and contributes to motor impairments. Striatal medium spiny
      neurons (MSNs) can be delineated into two populations, the dopamine D1 receptor
      (DA-D1R)-containing MSNs of the direct pathway and dopamine D2 receptor (DA-D2R)
      containing MSNs of the indirect pathway. There is evidence to suggest that the DA
      D2R-indirect pathway MSNs may be preferentially affected after DA-depletion with
      a predominate loss of dendritic spine density when compared to MSNs of the DA-D1R
      direct pathway in rodents; however, others have reported that both pathways may
      be affected in primates. The purpose of this study was to investigate the effects
      of intensive exercise on dendritic spine density and arborization in MSNs of
      these two pathways in the MPTP mouse model of PD. We found that MPTP led to a
      decrease in dendritic spine density in both DA-D1R- and DA-D2R-containing MSNs
      and 30 days of intensive treadmill exercise led to increased dendritic spine
      density and arborization in MSNs of both pathways. In addition, exercise
      increased the expression of synaptic proteins PSD-95 and synaptophysin. Taken
      together these findings support the potential effect of exercise in modifying
      synaptic connectivity within the DA-depleted striatum and in modifying disease
      progression in individuals with PD.

PMID- 24316167
TI  - Efficacy of levetiracetam in electrical status epilepticus during sleep of
      children: a multicenter experience.
AB  - BACKGROUND: Electrical status epilepticus during sleep is characterized by
      epilepsy, a specific electroencephalographic pattern, and neuropsychological
      impairment. This study aims to evaluate the efficacy and safety of levetiracetam
      in treating children with electrical status epilepticus during sleep. METHODS: A
      multicenter, retrospective, open-label study enrolled 73 children (mean age: 8
      years) affected by electrical status epilepticus during sleep. The efficacy was
      rated according to the seizure frequency and electroencephalography response.
      RESULTS: After a mean treatment period of 19 months (range: 6 to 24 months), 33
      (63.5%) of 52 patients became seizure-free or had experienced remarkable
      reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73
      patients disappeared off their electroencephalography. The electroencephalography
      efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add
      on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%)
      response rates of the idiopathic group were better than those of the symptomatic
      group (57.1% and 45.2%, respectively). No patient discontinued the trial because
      of intolerability of side effects. CONCLUSIONS: Levetiracetam is effective in
      individuals with electrical status epilepticus during sleep with tolerable side
      effects.

PMID- 24316168
TI  - Homology modeling of Kv1.5 channel block by cationic and electroneutral ligands.
AB  - The inner pore of potassium channels is targeted by many ligands of intriguingly
      different chemical structures. Previous studies revealed common and diverse
      characteristics of action of ligands including cooperativity of ligand binding,
      voltage- and use-dependencies, and patterns of ligand-sensing residues. Not all
      these data are rationalized in published models of ligand-channel complexes. Here
      we have used energy calculations with experimentally defined constraints to dock
      flecainide, ICAGEN-4, benzocaine, vernakalant, and AVE0118 into the inner pore of
      Kv1.5 channel. We arrived at ligand-binding models that suggest possible
      explanations for different values of the Hill coefficient, different voltage
      dependencies of ligands action, and effects of mutations of residues in subunit
      interfaces. Two concepts were crucial to build the models. First, the inner-pore
      block of a potassium channel requires a cationic "blocking particle". A ligand,
      which lacks a positively charged group, blocks the channel in a complex with a
      permeant ion. Second, hydrophobic moieties of a flexible ligand have a tendency
      to bind in hydrophobic subunit interfaces. 

PMID- 24316169
TI  - Interaction of a calix[4]arene derivative with a DOPC bilayer: biomolecular
      simulations towards chloride transport.
AB  - The ability of a calix[4]arene derivative (CX-1), bearing four protonated NH3(+)
      groups located in the upper rim and aliphatic tails in the lower rim, to interact
      with a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) model bilayer and promote
      transmembrane chloride transport was investigated by molecular dynamics (MD)
      simulations. Unconstrained MD simulations show that the interaction of CX-1 with
      DOPC occurs via the NH3(+) groups, which are able to establish electrostatic
      interactions and multiple hydrogen bonds with the DOPC phosphate groups, while
      the aliphatic tails point towards the water phase (when CX-1 starts from the
      water phase) or to the membrane (when CX-1 is initially positioned within the
      bilayer). The interaction does not induce any relevant perturbation on the
      biophysical properties of the bilayer system (area per lipid, thickness, and
      hydration) apart from a systematic increase in the order parameter of the C2
      carbon atom of the sn-1 lipid tail, meaning that the bilayer conserves its
      integrity. Since total internalization of CX-1 was not observed in the
      unconstrained MD time-scale, constant velocity steered molecular dynamics (SMD)
      simulations were performed in order to simulate the CX-1 permeation across the
      bilayer. At pulling velocities lower than 0.0075 nmps(-1), chloride transport was
      observed. The Potential of Mean Force (PMF), calculated with the weighted
      histogram analysis method, indicates a barrier of ca. 58kJmol(-1) for this mobile
      carrier to cross the membrane.

PMID- 24316170
TI  - Ca(2+) induces PI(4,5)P2 clusters on lipid bilayers at physiological PI(4,5)P2
      and Ca(2+) concentrations.
AB  - Calcium has been shown to induce clustering of PI(4,5)P2 at high and non
      physiological concentrations of both the divalent ion and the
      phosphatidylinositol, or on supported lipid monolayers. In lipid bilayers at
      physiological conditions, clusters are not detected through microscopic
      techniques. Here, we aimed to determine through spectroscopic methodologies if
      calcium plays a role in PI(4,5)P2 lateral distribution on lipid bilayers under
      physiological conditions. Using several different approaches which included
      information on fluorescence quantum yield, polarization, spectra and diffusion
      properties of a fluorescent derivative of PI(4,5)P2 (TopFluor(TF)-PI(4,5)P2), we
      show that Ca(2+) promotes PI(4,5)P2 clustering in lipid bilayers at physiological
      concentrations of both Ca(2+) and PI(4,5)P2. Fluorescence depolarization data of
      TF-PI(4,5)P2 in the presence of calcium suggests that under physiological
      concentrations of PI(4,5)P2 and calcium, the average cluster size comprises ~15
      PI(4,5)P2 molecules. The presence of Ca(2+)-induced PI(4,5)P2 clusters is
      supported by FCS data. Additionally, calcium mediated PI(4,5)P2 clustering was
      more pronounced in liquid ordered (lo) membranes, and the PI(4,5)P2-Ca(2+)
      clusters presented an increased affinity for lo domains. In this way, PI(4,5)P2
      could function as a lipid calcium sensor and the increased efficiency of calcium
      mediated PI(4,5)P2 clustering on lo domains might provide targeted nucleation
      sites for PI(4,5)P2 clusters upon calcium stimulus. 

PMID- 24316171
TI  - Interaction of cationic carbosilane dendrimers and their complexes with siRNA
      with erythrocytes and red blood cell ghosts.
AB  - We have investigated the interactions between cationic NN16 and BDBR0011
      carbosilane dendrimers with red blood cells or their cell membranes. The
      carbosilane dendrimers used possess 16 cationic functional groups. Both the
      dendrimers are made of water-stable carbon-silicon bonds, but NN16 possesses some
      oxygen-silicon bonds that are unstable in water. The nucleic acid used in the
      experiments was targeted against GAG-1 gene from the human immunodeficiency
      virus, HIV-1. By binding to the outer leaflet of the membrane, carbosilane
      dendrimers decreased the fluidity of the hydrophilic part of the membrane but
      increased the fluidity of the hydrophobic interior. They induced hemolysis, but
      did not change the morphology of the cells. Increasing concentrations of
      dendrimers induced erythrocyte aggregation. Binding of short interfering
      ribonucleic acid (siRNA) to a dendrimer molecule decreased the availability of
      cationic groups and diminished their cytotoxicity. siRNA-dendrimer complexes
      changed neither the fluidity of biological membranes nor caused cell hemolysis.
      Addition of dendriplexes to red blood cell suspension induced echinocyte
      formation. 

PMID- 24316172
TI  - Effects of sofosbuvir-based treatment, with and without interferon, on outcome
      and productivity of patients with chronic hepatitis C.
AB  - BACKGROUND & AIMS: Interferon-based treatment of chronic hepatitis C virus (HCV)
      infection can negatively affect patient-reported outcomes (PROs) and work
      productivity (WP). We assessed these factors in patients with chronic hepatitis C
      treated with sofosbuvir and ribavirin, with or without pegylated interferon.
      METHODS: The HCV-specific Quality of Life (Chronic Liver Disease Questionnaire
      HCV version [CLDQ-HCV]), Functional Assessment of Chronic Illness Therapy
      Fatigue, and Work Productivity and Activity Index: Specific Health Problem
      questionnaires were completed before, during, and after treatment of patients
      infected with HCV genotypes 2 or 3 who received sofosbuvir and ribavirin for 16
      or 12 weeks (the FUSION study, n = 201) or patients infected with HCV genotype 1
      who received pegylated interferon, sofosbuvir, and ribavirin for 12 weeks (the
      NEUTRINO study, n = 327). RESULTS: Patients in each group of the FUSION study had
      similar PRO and WP scores at each time point (all comparisons, P > .05). Compared
      with baseline, patients had modest reductions in fatigue, HCV-specific quality of
      life, and WP and Activity Index scores during treatment (P = .02 to <.0001).
      However, by 4 weeks after treatment, all scores returned to baseline levels or
      higher. Subjects in the NEUTRINO study had greater reductions in these scores
      during treatment; most remained significant through 4 weeks after treatment (P <
      .05). Significant improvements in PROs were observed among patients with
      sustained virologic responses 12 weeks after treatment in the FUSION and NEUTRINO
      studies (all P < .05). In multivariate analyses after adjustment for confounders,
      interferon therapy was independently associated with worse PROs after 12 weeks of
      treatment. CONCLUSIONS: On the basis of an analysis of 2 large clinical trials
      (FUSION and NEUTRINO), patient outcome and productivity are more negatively
      affected by the inclusion of pegylated interferon in treatment than by interferon
      free regimens. Patients with sustained virologic responses 12 weeks after
      treatment had significant improvements in PROs in both studies.

PMID- 24316173
TI  - Lung regeneration and translational implications of the postpneumonectomy model.
AB  - Lung regeneration research is yielding data with increasing translational value.
      The classical models of lung development, postnatal alveolarization, and
      postpneumonectomy alveolarization have contributed to a broader understanding of
      the cellular participants including stem-progenitor cells, cell-cell signaling
      pathways, and the roles of mechanical deformation and other physiologic factors
      that have the potential to be modulated in human and animal patients. Although
      recent information is available describing the lineage fate of lung fibroblasts,
      genetic fate mapping, and clonal studies are lacking in the study of lung
      regeneration and deserve further examination. In addition to increasing knowledge
      concerning classical alveolarization (postnatal, postpneumonectomy), there is
      increasing evidence for remodeling of the adult lung after partial pneumonectomy.
      Though limited in scope, compelling data have emerged describing restoration of
      lung tissue mass in the adult human and in large animal models. The basis for
      this long-term adaptation to pneumonectomy is poorly understood, but
      investigations into mechanisms of lung regeneration in older animals that have
      lost their capacity for rapid re-alveolarization are warranted, as there would be
      great translational value in modulating these mechanisms. In addition,
      quantitative morphometric analysis has progressed in conjunction with
      developments in advanced imaging, which allow for longitudinal and nonterminal
      evaluation of pulmonary regenerative responses in animals and humans. This review
      focuses on the cellular and molecular events that have been observed in animals
      and humans after pneumonectomy because this model is closest to classical
      regeneration in other mammalian systems and has revealed several new fronts of
      translational research that deserve consideration. 

PMID- 24316174
TI  - Electroconvulsive seizures enhance autophagy signaling in rat hippocampus.
AB  - The putative antidepressive mechanisms of a series of electroconvulsive seizures
      (ECS) are the following: 1) downregulation of monoaminergic receptor expression
      in several brain regions, 2) upregulation of the expression of brain-derived
      neurotrophic factor (BDNF), and 3) increased neurogenesis in the hippocampus. In
      this study, we used Western blot techniques to present another mechanism in which
      ECS enhances the autophagy signaling that is involved in the machinery related to
      synaptic and neural plasticity. Antibodies for conjugated Atg5-Atg12 (58kD) and
      cleaved light chain protein 3-II (LC3-II; 14 kD) were used to detect autophagy
      signals. An antibody for cleaved caspase-3 (17 kD) was used to detect alterations
      in apoptotic signals. Mature BDNF (14kD) expression in the hippocampus was
      evaluated in order to qualify the effectiveness of the ECS or stress-loading
      treatment. While significantly increased autophagy signals and no increases in
      apoptotic signals were detected in the ECS-treated rat hippocampus, the reverse
      (increased apoptotic signals and no altered autophagy signals) was observed in
      stressed rat hippocampus. No neuronal cell loss but new mossy fiber sprouting has
      been reported to accompany multiple ECS treatments, and recent studies have
      revealed that autophagy processes regulate the number of specific
      neurotransmitter receptors and the plasticity of synaptic components. The present
      study illustrated the neuroplastic and neurotrophic profiles of ECS and the
      neurotoxic impact of severe stress loading on hippocampal regions. This is the
      first report to demonstrate increased autophagy signals in ECS-treated rat
      hippocampus and no alterations in autophagy signals in stress-loaded rat
      hippocampus. 

PMID- 24316175
TI  - Assessment of safety, cardiovascular and subjective effects after intravenous
      cocaine and lofexidine.
AB  - The primary objective of this study was to determine the safety of lofexidine, an
      alpha2 receptor agonist, alone and concurrent with cocaine in non-treatment
      seeking cocaine-dependent or cocaine-abusing participants. After screening,
      eligible participants received double-blind, randomized infusions of saline and
      20mg of cocaine on Day 1, and saline and 40mg of cocaine on Day 2. Subjects were
      randomized and started receiving daily administration of placebo (N=4) or
      lofexidine on Day 3 and continued on this schedule until Day 7. Two dosing
      regimens for lofexedine were investigated: 0.8 QID (N=3) and 0.2mg QID (N=11). On
      Days 6 and 7, subjects received double-blind infusions of saline and 20mg of
      cocaine on Day 6, and saline and 40mg of cocaine on Day 7. The data reveal a
      notable incidence of hemodynamic-related AEs over the course of the study. Two of
      the three participants at the 0.8mg dose level discontinued, and five of 11
      participants at the 0.2mg dose level were withdrawn (or voluntarily discontinued)
      after hemodynamic AEs. Subjective effects and cardiovascular data were derived
      from all participants who were eligible to receive infusions (i.e., did not meet
      stopping criteria) on Days 6 and 7 (6 received lofexidine 0.2mg, QID and 4
      received placebo, QID). As expected, cocaine significantly increased heart rate
      and blood pressure, as well as several positive subjective effects. There was a
      trend for lofexidine to decrease cocaine-induced cardiovascular changes and
      cocaine-induced ratings for "any drug effect", "good effects", and "desire
      cocaine", but sample size issues limit the conclusions that can be drawn. Despite
      the trends to reduce cocaine-induced subjective effects, cardiovascular AEs may
      limit future utility of lofexidine as a treatment for this population. 

PMID- 24316176
TI  - Simulated digestion of dried leaves of Artemisia annua consumed as a treatment
      (pACT) for malaria.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisinin (AN) is produced by Artemisia annua,
      a medicinal herb long used as a tea infusion in traditional Chinese medicine to
      treat fever; it is also the key ingredient in current artemisinin-based
      combination therapies (ACTs) effective in treating malaria. Recently we showed
      that dried leaves from the whole plant Artemisia annua that produces artemisinin
      and contains artemisinin-synergistic flavonoids seem to be more effective and
      less costly than ACT oral malaria therapy; however little is known about how
      digestion affects release of artemisinin and flavonoids from dried leaves.
      MATERIAL AND METHODS: In the current study we used a simulated digestion system
      to determine how artemisinin and flavonoids are released prior to absorption into
      the bloodstream. Various delivery methods and staple foods were combined with
      dried leaves for digestion in order to investigate their impact on the
      bioavailability of artemisinin and flavonoids. Digestate was recovered at the end
      of the oral, gastric, and intestinal stages, separated into solid and liquid
      fractions, and extracted for measurement of artemisinin and total flavonoids.
      RESULTS: Compared to unencapsulated digested dried leaves, addition of sucrose,
      various cooking oils, and rice did not reduce the amount of artemisinin released
      in the intestinal liquid fraction, but the amount of released flavonoids nearly
      doubled. When dried leaves were encapsulated into either hydroxymethylcellulose
      or gelatin capsules, there was >50% decrease in released artemisinin but no
      change in released flavonoids. In the presence of millet or corn meal, the amount
      of released artemisinin declined, but there was no change in released flavonoids.
      Use of a mutant Artemisia annua lacking artemisinin showed that the plant matrix
      is critical in determining how artemisinin is affected during the digestion
      process. CONCLUSIONS: This study provides evidence showing how both artemisinin
      and flavonoids are affected by digestion and dietary components for an orally
      consumed plant delivered therapeutic and that artemisinin delivered via dried
      leaves would likely be more bioavailable if provided as a tablet instead of a
      capsule.

PMID- 24316177
TI  - Intermittent versus continuous operation of biosand filters.
AB  - The biosand filter is a household-scale point-of-use water filtration system
      based on slow sand filtration, but modified for intermittent operation. Studies
      on slow sand filters show that intermittent operation reduces filter
      effectiveness. However, continuous versus intermittent operation of biosand
      filters has never been compared. Eight 10-cm diameter columns were constructed to
      represent field biosand filters. Five were operated intermittently with a 24-h
      residence period, while the remaining three were operated continuously.
      Continuous operation of the filters resulted in significantly better reduction of
      Escherichia coli (3.71 log10 versus 1.67 log10), bacteriophage MS2 (2.25 log10
      versus 0.85 log10), and turbidity (96% versus 87%). Dissolved oxygen levels at 5
      and 10 cm of media depth in intermittent filters reached an average of 0 mg/L by
      24 h of residence time on day 60 of the experiment. A simple numerical model was
      developed to describe E. coli removal during ripening from days 0-58 for
      continuously operated versus intermittent filters. This research confirms that
      although biosand filters were developed for intermittent operation, the filters
      perform significantly better when operated continuously. However, both
      operational modes resulted in a significant reduction of microbial indicators. 

PMID- 24316178
TI  - Identification of phototransformation products of thalidomide and mixture
      toxicity assessment: an experimental and quantitative structural activity
      relationships (QSAR) approach.
AB  - The fate of thalidomide (TD) was investigated after irradiation with a medium
      pressure Hg-lamp. The primary elimination of TD was monitored and structures of
      phototransformation products (PTPs) were assessed by LC-UV-FL-MS/MS.
      Environmentally relevant properties of TD and its PTPs as well as hydrolysis
      products (HTPs) were predicted using in silico QSAR models. Mutagenicity of TD
      and its PTPs was investigated in the Ames microplate format (MPF) aqua assay
      (Xenometrix, AG). Furthermore, a modified luminescent bacteria test (kinetic
      luminescent bacteria test (kinetic LBT)), using the luminescent bacteria species
      Vibrio fischeri, was applied for the initial screening of environmental toxicity.
      Additionally, toxicity of phthalimide, one of the identified PTPs, was
      investigated separately in the kinetic LBT. The UV irradiation eliminated TD
      itself without complete mineralization and led to the formation of several PTPs.
      TD and its PTPs did not exhibit mutagenic response in the Salmonella typhimurium
      strains TA 98, and TA 100 with and without metabolic activation. In contrast,
      QSAR analysis of PTPs and HTPs provided evidence for mutagenicity, genotoxicity
      and carcinogenicity using additional endpoints in silico software. QSAR analysis
      of different ecotoxicological endpoints, such as acute toxicity towards V.
      fischeri, provided positive alerts for several identified PTPs and HTPs. This was
      partially confirmed by the results of the kinetic LBT, in which a steady increase
      of acute and chronic toxicity during the UV-treatment procedure was observed for
      the photolytic mixtures at the highest tested concentration. Moreover, the number
      of PTPs within the reaction mixture that might be responsible for the
      toxification of TD during UV-treatment was successfully narrowed down by
      correlating the formation kinetics of PTPs with QSAR predictions and experimental
      toxicity data. Beyond that, further analysis of the commercially available PTP
      phthalimide indicated that transformation of TD into phthalimide was not the
      cause for the toxification of TD during UV-treatment. These results provide a
      path for toxicological assessment of complex chemical mixtures and in detail show
      the toxic potential of TD and its PTPs as well as its HTPs. This deserves further
      attention as UV irradiation might not always be a green technology, because it
      might pose a toxicological risk for the environment in general and specifically
      for water compartments. 

PMID- 24316179
TI  - Effect of process parameters and operational mode on nitrous oxide emissions from
      a nitritation reactor treating reject wastewater.
AB  - Nitrous oxide (N2O) and methane emissions were monitored in a continuous granular
      airlift nitritation reactor from ammonium-rich wastewater (reject wastewater).
      N2O emissions were found to be dependent on dissolved oxygen (DO) concentration
      in the range of 1-4.5 mg O2/L, increasing within this range when reducing the DO
      values. At higher DO concentrations, N2O emissions remained constant at 2.2% of
      the N oxidized to nitrite, suggesting two different mechanisms behind N2O
      production, one dependent and one independent of DO concentration. Changes on
      ammonium, nitrite, free ammonia and free nitrous acid concentrations did not have
      an effect on N2O emissions within the concentration range tested. When operating
      the reactor in a sequencing batch mode under high DO concentration (>5 mg O2/L),
      N2O emissions increased one order of magnitude reaching values of 19.3 +/- 7.5%
      of the N oxidized. Moreover, CH4 emissions detected were due to the stripping of
      the soluble CH4 that remained dissolved in the reject wastewater after anaerobic
      digestion. Finally, an economical and carbon footprint assessment of a
      theoretical scaled up of the pilot plant was conducted. 

PMID- 24316180
TI  - Ozonation products of carbamazepine and their removal from secondary effluents by
      soil aquifer treatment--indications from column experiments.
AB  - Ozonation is known as an efficient treatment to reduce the concentration of many
      trace organic compounds from WWTP effluents, but the formation of unknown and
      possibly persistent and toxic transformation products has to be considered. In
      this paper tertiary treatment of wastewater by the combination of ozone and soil
      aquifer treatment was investigated with respect to the removal of the
      antiepileptic drug carbamazepine (CBZ, 10 MUg/L) and its transformation products.
      Batch tests and pilot experiments confirmed efficient removal of carbamazepine
      from secondary effluent by ozone. With typical ozone consumption of 0.7 mg O3/mg
      DOC0, approx. 50% of the transformed CBZ was detected as its primary product 1-(2
      benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM). Structure proposals and a
      formation pathway were elaborated for a total of 13 ozonation products of CBZ. In
      subsequent biological treatment BQM turned out to be more effectively biodegraded
      than CBZ. Its aldehyde group was quickly oxidized to a carboxylic acid (BaQM),
      which was removed in sand column experiments. Most of the minor ozonation
      products of CBZ persisted in sand column experiments with residence times of 5-6
      days. Non-target screening of column effluent revealed no formation of persistent
      biotransformation products. 

PMID- 24316181
TI  - Effect of membrane bioreactor solids retention time on reverse osmosis membrane
      fouling for wastewater reuse.
AB  - The effect of the solids retention time (SRT) in a membrane bioreactor (MBR) on
      the fouling of the membranes in a subsequent reverse osmosis (RO) process used
      for wastewater reuse was studied experimentally using a pilot-scale treatment
      system. The MBR-RO pilot system was fed effluent from the primary clarifiers at a
      large municipal wastewater treatment plant. The SRT in the MBRs was adjusted to
      approximately 2, 10, and 20 days in three experiments. The normalized specific
      flux through the MBR and RO membranes was evaluated along with inorganic and
      organic constituents in the influent and effluent of each process. Increasing the
      SRT in the MBR led to an increase in the removal of bulk DOC, protein, and
      carbohydrates, as has been observed in previous studies. Increasing the SRT led
      to a decrease in the fouling of the MBR membranes, which is consistent with
      previous studies. However, the opposite trend was observed for fouling of the RO
      membranes; increasing the SRT of the MBR resulted in increased fouling of the RO
      membranes. These results indicate that the constituents that foul MBR membranes
      are not the same as those that foul RO membranes; to be an RO membrane foulant in
      a MBR-RO system, the constituents must first pass through the MBR membranes
      without being retained. Thus, an intermediate value of SRT may be best choice of
      operating conditions in an MBR when the MBR is followed by RO for wastewater
      reuse. 

PMID- 24316182
TI  - Methods for assessing biochemical oxygen demand (BOD): a review.
AB  - The Biochemical Oxygen Demand (BOD) is one of the most widely used criteria for
      water quality assessment. It provides information about the ready biodegradable
      fraction of the organic load in water. However, this analytical method is time
      consuming (generally 5 days, BOD5), and the results may vary according to the
      laboratory (20%), primarily due to fluctuations in the microbial diversity of the
      inoculum used. Work performed during the two last decades has resulted in several
      technologies that are less time-consuming and more reliable. This review is
      devoted to the analysis of the technical features of the principal methods
      described in the literature in order to compare their performances (measuring
      window, reliability, robustness) and to identify the pros and the cons of each
      method. 

PMID- 24316183
TI  - Effects of heat shock on survival, proliferation and differentiation of mouse
      neural stem cells.
AB  - Hyperthermia during pregnancy is a significant cause of reproductive problems
      ranging from abortion to congenital defects of the central nervous system (CNS),
      including neural tube defects and microcephaly. Neural stem cells (NSCs) can
      proliferate and differentiate into neurons and glia, playing a key role in the
      formation of the CNS. Here, we examined the effects of heat shock on homogeneous
      proliferating NSCs derived from mouse embryonic stem cells. After heat shock at
      42  degrees C for 20 min, the proliferating NSCs continued to proliferate,
      although subtle changes were observed in gene expression and cell survival and
      proliferation. In contrast, heat shock at 43  degrees C caused a variety of
      responses: the up-regulation of genes encoding heat shock proteins (HSP),
      induction of apoptosis, temporal inhibition of cell proliferation and retardation
      of differentiation. Finally, effects of heat shock at 44  degrees C were severe,
      with almost all cells disappearing and the remaining cells losing the capacity to
      proliferate and differentiate. These temperature-dependent effects of heat shock
      on NSCs may be valuable in elucidating the mechanisms by which hyperthermia
      during pregnancy causes various reproductive problems.

PMID- 24316184
TI  - Glycogen synthase kinase-3 (GSK3) controls deoxyglucose-induced mitochondrial
      biogenesis in human neuroblastoma SH-SY5Y cells.
AB  - Mitochondrial biogenesis, a mitochondrial growth and division process, is crucial
      for adaptation to metabolic stress. The present study demonstrated that treatment
      with a specific inhibitor of GSK3, SB216763, attenuated induction of
      mitochondrial biogenesis by a glycolysis inhibitor, 2-deoxyglucose (2-DG),
      without affecting this biogenesis at basal condition. Additionally,
      overexpression of WT-GSK3beta promoted whereas GSK3beta-KD attenuated 2-DG
      induced mitochondrial protein expression. The mitochondrial biogenesis
      attenuation by GSK3 inhibitor was not due to inhibition of protein degradation.
      Furthermore, GSK3 inhibition further reduced transcription of mitochondrial
      (COXII), but not nuclear (VDAC) gene by 2-DG suggesting its participation in 2-DG
      induced mitochondrial transcription. Together, our results show that GSK3
      regulates mitochondrial biogenesis induced by glycolysis inhibition. 

PMID- 24316185
TI  - Inactivation of genes coding for mitochondrial Nd7 and Nd9 complex I subunits in
      Chlamydomonas reinhardtii. Impact of complex I loss on respiration and energetic
      metabolism.
AB  - In Chlamydomonas, unlike in flowering plants, genes coding for Nd7 (NAD7/49 kDa)
      and Nd9 (NAD9/30 kDa) core subunits of mitochondrial respiratory-chain complex I
      are nucleus-encoded. Both genes possess all the features that facilitate their
      expression and proper import of the polypeptides in mitochondria. By inactivating
      their expression by RNA interference or insertional mutagenesis, we show that
      both subunits are required for complex I assembly and activity. Inactivation of
      complex I impairs the cell growth rate, reduces the respiratory rate, leads to
      lower intracellular ROS production and lower expression of ROS scavenging
      enzymes, and is associated to a diminished capacity to concentrate CO2 without
      compromising photosynthetic capacity.

PMID- 24316186
TI  - Magnetic field homogeneity perturbations in finite Halbach dipole magnets.
AB  - Halbach hollow cylinder dipole magnets of a low or relatively low aspect ratio
      attract considerable attention due to their applications, among others, in
      compact NMR and MRI systems for investigating small objects. However, a complete
      mathematical framework for the analysis of magnetic fields in these magnets has
      been developed only for their infinitely long precursors. In such a case the
      analysis is reduced to two-dimensions (2D). The paper details the analysis of the
      3D magnetic field in the Halbach dipole cylinders of a finite length. The
      analysis is based on three equations in which the components of the magnetic flux
      density Bx, By and Bz are expanded to infinite power series of the radial
      coordinate r. The zeroth term in the series corresponds to a homogeneous magnetic
      field Bc, which is perturbed by the higher order terms due to a finite magnet
      length. This set of equations is supplemented with an equation for the field
      profile B(z) along the magnet axis, presented for the first time. It is
      demonstrated that the geometrical factors in the coefficients of particular
      powers of r, defined by intricate integrals are the coefficients of the Taylor
      expansion of the homogeneity profile (B(z)-Bc)/Bc. As a consequence, the
      components of B can be easily calculated with an arbitrary accuracy. In order to
      describe perturbations of the field due to segmentation, two additional equations
      are borrowed from the 2D theory. It is shown that the 2D approach to the
      perturbations generated by the segmentation can be applied to the 3D Halbach
      structures unless r is not too close to the inner radius of the cylinder ri. The
      mathematical framework presented in the paper was verified with great precision
      by computations of B by a highly accurate integration of the magnetostatic
      Coulomb law and utilized to analyze the inhomogeneity of the magnetic field in
      the magnet with the accuracy better than 1 ppm.

PMID- 24316187
TI  - Implementing homo- and heterodecoupling in region-selective HSQMBC experiments.
AB  - An NMR method to enhance the sensitivity and resolution in band-selective long
      range heteronuclear correlation spectra is proposed. The excellent in-phase
      nature of the selHSQMBC experiment allows that homonuclear and/or heteronuclear
      decoupling can be achieved in the detected dimension of a 2D multiple-bond
      correlation map, obtaining simplified cross-peaks without their characteristic
      fine J multiplet structure. The experimental result is a resolution improvement
      while the highest sensitivity is also achieved. Specifically, it is shown that
      the (1)H-homodecoupled band-selective (HOBS) HSQMBC experiment represents a new
      way to measure heteronuclear coupling constants from the simplified in-phase
      doublets generated along the detected dimension. 

PMID- 24316188
TI  - Arbitrary magnetic field gradient waveform correction using an impulse response
      based pre-equalization technique.
AB  - The time-varying magnetic fields used in magnetic resonance applications result
      in the induction of eddy currents on conductive structures in the vicinity of
      both the sample under investigation and the gradient coils. These eddy currents
      typically result in undesired degradations of image quality for MRI applications.
      Their ubiquitous nature has resulted in the development of various approaches to
      characterize and minimize their impact on image quality. This paper outlines a
      method that utilizes the magnetic field gradient waveform monitor method to
      directly measure the temporal evolution of the magnetic field gradient from a
      step-like input function and extracts the system impulse response. With the basic
      assumption that the gradient system is sufficiently linear and time invariant to
      permit system theory analysis, the impulse response is used to determine a pre
      equalized (optimized) input waveform that provides a desired gradient response at
      the output of the system. An algorithm has been developed that calculates a pre
      equalized waveform that may be accurately reproduced by the amplifier (is
      physically realizable) and accounts for system limitations including system
      bandwidth, amplifier slew rate capabilities, and noise inherent in the initial
      measurement. Significant improvements in magnetic field gradient waveform
      fidelity after pre-equalization have been realized and are summarized. 

PMID- 24316189
TI  - Effect of lactose permease presence on the structure and nanomechanics of two
      component supported lipid bilayers.
AB  - In this paper we present a comparative study of supported lipid bilayers (SLBs)
      and proteolipid sheets (PLSs) obtained from deposition of lactose permease (LacY)
      of Escherichia coli proteoliposomes in plane. Lipid matrices of two components,
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), at a 3:1, mol/mol
      ratio, were selected to mimic the inner membrane of the bacteria. The aim was to
      investigate how species of different compactness and stiffness affect the
      integration, distribution and nanomechanical properties of LacY in mixtures of 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) or 1,2-palmitoyl-sn
      glycero-3-phosphoethanolamine (DPPE) with 1-palmitoyl-2-oleoyl-sn-glycero-3
      [phospho-rac-(1-glycerol)] (POPG). Both compositions displayed phase separation
      and were investigated by atomic force microscopy (AFM) imaging and force
      spectroscopy (FS) mode. PLSs displayed two separated, segregated domains with
      different features that were characterised by FS and force-volume mode. We
      correlated the nanomechanical characteristics of solid-like gel phase (Lbeta) and
      fluid liquid-crystalline phase (Lalpha) with phases emerging in presence of LacY.
      We observed that for both compositions, the extended PLSs showed a Lbeta
      apparently formed only by lipids, whilst the second domain was enriched in LacY.
      The influence of the lipid environment on LacY organisation was studied by
      performing protein unfolding experiments using the AFM tip. Although the pulling
      experiments were unspecific, positive events were obtained, indicating the
      influence of the lipid environment when pulling the protein. A possible influence
      of the lateral surface pressure on this behaviour is suggested by the higher
      force required to pull LacY from DPPE:POPG than from POPE:POPG matrices. This is
      related to higher forces governing protein-lipid interaction in presence of DPPE.

PMID- 24316190
TI  - Bacterial expression of human kynurenine 3-monooxygenase: solubility, activity,
      purification.
AB  - Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway
      of tryptophan metabolism. KMO has been implicated as a therapeutic target in
      several disease states, including Huntington's disease. Recombinant human KMO
      protein production is challenging due to the presence of transmembrane domains,
      which localise KMO to the outer mitochondrial membrane and render KMO insoluble
      in many in vitro expression systems. Efficient bacterial expression of human KMO
      would accelerate drug development of KMO inhibitors but until now this has not
      been achieved. Here we report the first successful bacterial (Escherichia coli)
      expression of active FLAGTM-tagged human KMO enzyme expressed in the soluble
      fraction and progress towards its purification. 

PMID- 24316191
TI  - Purification and reconstitution of human membrane-bound DHRS7 (SDR34C1) from Sf9
      cells.
AB  - Dehydrogenase/reductase SDR family member 7 (DHRS7, SDR34C1, retSDR4) is one of
      the many endoplasmic reticulum bound members of the SDR superfamily. Preliminary
      results indicate its potential significance in human metabolism. DHRS7 containing
      TEV-cleavable His10 and FLAG-tag expressed in the Sf9 cell line was solubilised,
      purified, and reconstituted into liposomes to enable the improved
      characterisation of this enzyme in the future. Igepal CA-630 was determined to be
      the best detergent for the solubilisation process. The solubilised DHRS7 was
      purified using affinity chromatography, and the purified enzyme was subjected to
      TEV cleavage of the affinity tags and then repurified using subtractive Ni-IMAC.
      The cleaved and uncleaved versions of DHRS7 were successfully reconstituted into
      liposomes. In addition, using tobacco specific carcinogen 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanone (NNK) as the substrate, the cleaved liposomal DHRS7 was
      found to be inactive, whereas the pure and uncleaved liposomal DHRS7 were
      confirmed as enzymes, which reduce carbonyl group of the substrates. 

PMID- 24316192
TI  - Strategies for purifying variants of human rhinovirus 14 2C protein.
AB  - The positive strand RNA genome of picornaviruses, including human rhinovirus
      (HRV), poliovirus (PV) and foot-and-mouth disease virus, is translated
      immediately into a polyprotein that is cleaved by virally encoded proteinases
      into 10-13 mature proteins. These include the four proteins required to assemble
      the viral particle as well as 3D(pol) (the viral RNA polymerase) and 2C, an
      ATPase and putative helicase. 2C is a protein which is responsible, together with
      2B and 3A, for anchoring the replication complexes to membranous structures in
      the infected cell on which RNA replication takes place. Additionally, expression
      of 2C and its precursor 2BC in mammalian cells leads to vesicle formation
      observed in infected cells. 2C is encoded by all picornaviruses; nevertheless,
      its exact role in viral replication remains unclear. A contributing factor is the
      absence of structural data for this hydrophobic protein the generation of which
      has been hampered by an inability to produce soluble and stable material. Here,
      we compare 2C from several genera and show that the 2C protein has considerable
      heterogeneity. Using protein structure meta-analysis, we developed models of
      HRV14 2C that should be useful for mutational analysis. Based on these analyses,
      we expressed and purified two domains of HRV14 2C using three different protocols
      and examined the folding by thermal denaturation or (1)H NMR. Both domains were
      concentrated sufficiently to allow crystal screens or NMR pilot experiments to be
      performed. This work provides a platform to explore 2C proteins from all
      picornaviral genera to generate candidates for structural analysis. 

PMID- 24316193
TI  - Axonal degeneration in dorsal columns of spinal cord does not induce recruitment
      of hematogenous macrophages.
AB  - It is generally accepted that there are two populations of macrophages that
      respond to neural injuries and successful recruitment of hematogenous macrophages
      has been shown to help the process of nerve repair in the peripheral nervous
      system (PNS). Meanwhile, the recruitment of circulating macrophages after central
      nerve system (CNS) injuries is considered mild and delayed. We compared the
      recruitment of circulating macrophages in the peripheral nerves and spinal cord
      after dorsal root ganglionectomies, which induce selective and approximately
      similar extent of sensory fiber degeneration in PNS and CNS, in bone marrow
      chimeric mice. Our results showed that circulating macrophages were efficiently
      recruited in PNS but virtually no recruitment in CNS despite degeneration of
      peripheral and central sensory projections emanating from the same dorsal root
      ganglion (DRG) neurons. The mechanisms that prevent recruitment of circulating
      macrophages in CNS after injury remain poorly elucidated. 

PMID- 24316194
TI  - A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications
      for diabetes.
AB  - The glycation of protein and nucleic acids that occurs as a consequence of
      hyperglycemia disrupts cell function and contributes to many pathologies,
      including those associated with diabetes and aging. Intracellular glycation
      occurs after the generation of the reactive 1,2-dicarbonyls methylglyoxal and
      glyoxal, and disruption of mitochondrial function is associated with
      hyperglycemia. However, the contribution of these reactive dicarbonyls to
      mitochondrial damage in pathology is unclear owing to uncertainties about their
      levels within mitochondria in cells and in vivo. To address this we have
      developed a mitochondria-targeted reagent (MitoG) designed to assess the levels
      of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic
      triphenylphosphonium cationic function, which directs the molecules to
      mitochondria within cells, and an o-phenylenediamine moiety that reacts with
      dicarbonyls to give distinctive and stable products. The extent of accumulation
      of these diagnostic heterocyclic products can be readily and sensitively
      quantified by liquid chromatography-tandem mass spectrometry, enabling changes to
      be determined. Using the MitoG-based analysis we assessed the formation of
      methylglyoxal and glyoxal in response to hyperglycemia in cells in culture and in
      the Akita mouse model of diabetes in vivo. These findings indicated that the
      levels of methylglyoxal and glyoxal within mitochondria increase during
      hyperglycemia both in cells and in vivo, suggesting that they can contribute to
      the pathological mitochondrial dysfunction that occurs in diabetes and aging. 

PMID- 24316195
TI  - Functional characterization of thioredoxin 3 (TRX-3), a Caenorhabditis elegans
      intestine-specific thioredoxin.
AB  - Thioredoxins are a class of evolutionarily conserved proteins that have been
      demonstrated to play a key role in many cellular processes involving redox
      reactions. We report here the genetic and biochemical characterization of
      Caenorhabditis elegans TRX-3, the first metazoan thioredoxin with an intestine
      specific expression pattern. By using green fluorescent protein reporters we have
      found that TRX-3 is expressed in both the cytoplasm and the nucleus of intestinal
      cells, with a prominent localization at the apical membrane. Although intestinal
      function, reproductive capacity, longevity, and resistance of trx-3 loss-of
      function mutants to many stresses are indistinguishable from those of wild-type
      animals, we have observed a slight reduction in size and a minor reduction in the
      defecation cycle timing of trx-3 mutants. Interestingly, trx-3 is induced upon
      infection by Photorhabdus luminescens and Candida albicans, and TRX-3
      overexpression provides a modest protection against these pathogens. Together,
      our data indicate that TRX-3 function in the intestine is dispensable for C.
      elegans development but may be important to fight specific bacterial and fungal
      infections. 

PMID- 24316196
TI  - Developmental susceptibility of neurons to transient tetrahydrobiopterin
      insufficiency and antenatal hypoxia-ischemia in fetal rabbits.
AB  - Tetrahydrobiopterin (BH4) is important for normal brain development as congenital
      BH4 deficiencies manifest movement disorders at various childhood ages. BH4
      transitions from very low levels in fetal brains to higher "adult" levels
      postnatally, with the highest levels in the thalamus. Maternal supplementation
      with the BH4 precursor sepiapterin reduces postnatal motor deficits and perinatal
      deaths after 40-min fetal hypoxia-ischemia (HI) at 70% gestation, suggesting that
      brain BH4 is important in improving function after HI. We tested the hypothesis
      that the intrinsically low concentrations of BH4 made fetal neurons vulnerable to
      added insults. Brains were obtained from naive fetal rabbits or after 40-min HI,
      at 70% (E22) and 92% gestation (E29). Neuronal cultures were prepared from basal
      ganglia, cortex, and thalamus, regions with different intrinsic levels of BH4.
      Cultures were grown with or without added BH4 for 48h. Cell survival and
      mitochondrial function were determined by flow cytometry. At E22, thalamic cells
      had the lowest survival rate in a BH4-free milieu, in both control and HI groups,
      whereas BH4 supplementation ex vivo increased neuronal survival only in HI cells.
      Neuronal survival was similar in all regions without BH4 at E29. BH4
      supplementation increased cell survival and cells with intact mitochondrial
      membrane potential, from basal ganglia and cortex, but not thalamus. After E29
      HI, however, the benefit of BH4 was limited to cortical neurons. We conclude that
      BH4 is important for fetal neuronal survival after HI especially in the premature
      thalamus. Supplementation of BH4 has a greater benefit at an earlier gestational
      age. 

PMID- 24316197
TI  - Seeking the mechanism responsible for fluoroquinolone photomutagenicity: a pulse
      radiolysis, steady-state, and laser flash photolysis study.
AB  - The mechanism responsible for the remarkable photomutagenicity of fluoroquinolone
      (FQ) antibiotics remains unknown. For this reason, it was considered worthwhile
      to study in detail the interactions between DNA and a dihalogenated FQ such as
      lomefloxacin (LFX; one of the most photomutagenic FQs) and its N-acetyl
      derivative ALFX. Studies of photosensitized DNA damage by (A)LFX, such as
      formation of DNA single-strand breaks (SSBs), together with pulse radiolysis,
      laser flash photolysis, and absorption and fluorescence measurements, have shown
      the important effects of the cationic character of the piperazinyl ring on the
      affinity of this type of drug for DNA. Hence, the formation of SSBs was detected
      for LFX, whereas ALFX and ciprofloxacin (a monofluorated FQ) needed a
      considerably larger dose of light to produce some damage. In this context, it was
      determined that the association constant (Ka) for the binding of LFX to DNA is
      ca. 2*10(3)M(-1), whereas in the case of ALFX it is only ca. 0.5*10(3)M(-1). This
      important difference is attributed to an association between the cationic
      peripheral ring of LFX and the phosphate moieties of DNA and justifies the DNA
      SSB results. The analysis of the transient species detected and the photomixtures
      has allowed us to establish the intermolecular processes involved in the
      photolysis of FQ in the presence of DNA and 2'-deoxyguanosine (dGuo).
      Interestingly, although a covalent binding of the dihalogenated FQ to dGuo
      occurs, the photodegradation of FQ...DNA complexes did not reveal any significant
      covalent attachment. Another remarkable outcome of this study was that (A)LFX
      radical anions, intermediates required for the onset of DNA damage, were detected
      by pulse radiolysis but not by laser flash photolysis. 

PMID- 24316199
TI  - The influence of anhedonia on feedback negativity in major depressive disorder.
AB  - Anhedonia is associated with reward-processing deficits of the dopamine system,
      which may increase the risk of depression. Nevertheless, few previous studies
      have examined the influence of hedonic tone on event-related potential (ERP)
      measures of reward processing in major depressive disorder. A simple gambling
      task was used to elicit feedback negativity (FN), an ERP component elicited by
      feedback indicating gain versus loss, in 27 patients with major depression and 27
      healthy participants. We found that participants with depression were
      characterized by reduced FN responses, especially towards monetary gains, but not
      losses, compared with healthy individuals. In addition, the amplitude of FN to
      gain feedback in participants with depression was related to anhedonia severity
      and depressive symptoms. These findings indicate an association between low
      hedonic capacity and reduction in FN. As a neural measure of reward sensitivity,
      FN may be generated in part by reward-related activity. 

PMID- 24316200
TI  - Gender differences in neural-behavioral response to self-observation during a
      novel fMRI social stress task.
AB  - The neural correlates of response to psychosocial stress and gender differences
      therein are difficult to model experimentally as this type of stressor is
      difficult to induce in a brain imaging environment. The Trier Social Stress Test
      (TSST), a behavioral paradigm that reliably induces moderate levels of stress was
      thus modified for the MRI environment. To determine the neurobehavioral basis of
      gender differences in response to observing oneself under social evaluative
      stress, 26 subjects (14 females) performed the TSST while being videotaped.
      During fMRI scanning, subjects were shown alternating video clips of two
      CONDITIONS: SELF or a same-sex OTHER performing the TSST. Subjects rated their
      stress level immediately after the video clips. GENDER differences in the [SELF
      OTHER] contrast were analyzed. There was a GENDER*CONDITION interaction such that
      only women reported increased subjective stress during video feedback of their
      TSST session. A whole brain analysis (SELF vs. OTHER) showed activation in the
      bilateral insula, inferior, middle and superior frontal gyri. Greater recruitment
      was seen among males in some of these same areas in the context of significantly
      lower stress ratings. Activation of areas involved in inhibitory control and
      sensory awareness might contribute to the significantly lower stress ratings in
      males. Understanding these gender differences is relevant to disorders of stress
      and self-concept.

PMID- 24316198
TI  - The effects of lateral prefrontal transcranial magnetic stimulation on item
      memory encoding.
AB  - Previous neuroimaging research has established that the left ventrolateral
      prefrontal cortex (VLPFC) is involved in long-term memory (LTM) encoding for
      individual items. Dorsolateral prefrontal cortex (DLPFC) is implicated less
      frequently, and one theory that has gained support to explain this discrepancy is
      that DLPFC is involved in forming item-item relational but not item LTM. Given
      that neuroimaging results are correlational, complimentary methods such as
      repetitive transcranial magnetic stimulation (TMS) have been used to test causal
      hypotheses generated from imaging data. Most TMS studies of LTM encoding have
      found that disruption of lateral PFC activity impairs subsequent memory. However
      these studies have lacked methods to precisely localize and directly compare TMS
      effects from frontal subregions implicated by the neuroimaging literature. Here,
      we target specific subregions of lateral PFC with TMS to test the prediction from
      the item/relational framework that temporary disruption of VLPFC during encoding
      will impair subsequent memory whereas TMS to DLPFC during item encoding will not.
      Frontal TMS was administered prior to a LTM encoding task in which participants
      were presented with a list of individual nouns and asked to judge whether each
      noun was concrete or abstract. After a 40 min delay period, item recognition
      memory was tested. Results indicate that VLPFC and DLPFC TMS have differential
      effects on subsequent item memory. VLPFC TMS reliably disrupted subsequent item
      memory whereas DLPFC TMS led to numerical enhancement in item memory, relative to
      TMS to a control region.

PMID- 24316201
TI  - Endocannabinoid signaling in hypothalamic-pituitary-adrenocortical axis recovery
      following stress: effects of indirect agonists and comparison of male and female
      mice.
AB  - Studies in male rodents have shown that stress-induced increases in circulating
      corticosterone are increased by both CB1 receptor (CB1R) antagonist treatment and
      genetic deletion. The purposes of the current study were to determine whether
      female mice respond in the same manner as males, and whether indirect CB1R
      agonists accelerate the return of corticosterone to baseline. In agreement with
      earlier studies, CB1R null and rimonabant-treated male mice had significantly
      increased circulating corticosterone 30 min following the end of a restraint
      episode compared to wild type and vehicle-treated, respectively. Females treated
      with rimonabant had significantly higher circulating corticosterone compared to
      vehicle. However, corticosterone concentrations were not different between CB1R
      null and wild type females at 30 min recovery, although CB1R null mice had higher
      corticosterone concentrations at 90 min of recovery. Female CB1R null mice
      exhibited greater serum binding capacity for corticosterone than wild type. The
      monoacylglycerol lipase inhibitor, JZL184, attenuated corticosterone
      concentrations at restraint offset in male, and at 30 min recovery in female mice
      compared to vehicle. Male mice treated with JZL184 exhibited greater
      concentrations of circulating corticosterone at 120 min recovery, even in the
      absence of restraint. JZL184 had no effect on corticosterone concentrations in
      CB1R null mice. The fatty acid amide hydrolase inhibitor, URB597, did not affect
      corticosterone responses to restraint in male or female, wild type or CB1R null
      mice. These data suggest that 2-arachidonoylglycerol is the primary
      endocannabinoid involved in CB1R regulation of the recovery of the HPA axis from
      restraint stress. These data support a role for endocannabinoid-CB1R signaling in
      the regulation of the corticosterone response to restraint stress and suggest
      that female mice with life-long loss of the CB1R undergo compensatory changes
      that minimize the impact of loss of endocannabinoid signaling on circulating
      corticosterone.

PMID- 24316202
TI  - Colponemids represent multiple ancient alveolate lineages.
AB  - The alveolates comprise three well-studied protist lineages of significant
      environmental, medical, and economical importance: apicomplexans (e.g.,
      Plasmodium), dinoflagellates (e.g., Symbiodinium), and ciliates (e.g.,
      Tetrahymena). These major lineages have evolved distinct and unusual
      characteristics, the origins of which have proved to be difficult evolutionary
      puzzles. Mitochondrial genomes are a prime example: all three groups depart from
      canonical form and content, but in different ways. Reconstructing such ancient
      transitions is difficult without deep-branching lineages that retain ancestral
      characteristics. Here we describe two such lineages and how they illuminate the
      ancestral state of alveolate mitochondrial genomes. We established five clonal
      cultures of colponemids, predatory alveolates without cultured representatives
      and molecular data. Colponemids represent at least two independent lineages at
      the phylum level in multilocus phylogenetic analysis; one sister to apicomplexans
      and dinoflagellates, and the other at a deeper position. A genome survey from one
      strain showed that ancestral state of the mitochondrial genomes in the three
      major alveolate lineages consisted of an unusual linear chromosome with telomeres
      and a substantially larger gene set than known alveolates. Colponemid sequences
      also identified several environmental lineages as colponemids, altogether
      suggesting an untapped potential for understanding the origin and evolution of
      apicomplexans, dinoflagellates, and ciliates. 

PMID- 24316203
TI  - Arabidopsis TOL proteins act as gatekeepers for vacuolar sorting of PIN2 plasma
      membrane protein.
AB  - Controlling variations in plasma membrane (PM) protein abundance is of utmost
      importance for development in higher plants. For modulating PM protein activity,
      endocytosed proteins can be either cycled between PM and endosomes or sorted for
      their irreversible inactivation to lysosomes/vacuoles. Cargo ubiquitination
      triggers vacuolar delivery for degradation, which is controlled by Endosomal
      Sorting Complex Required for Transport (ESCRT). Essential parts of this machinery
      are conserved across kingdoms, but determinants liable for initial recognition
      and concentration of ubiquitinated cargo have not been identified in plants.
      Here, we describe members of an Arabidopsis TOL (TOM1-LIKE) family as ubiquitin
      binding proteins that act redundantly in control of plant morphogenesis.
      Specifically, tol mutant combinations exhibit defects that reflect alterations in
      responses mediated by the phytohormone auxin. Consistently, we provide evidence
      for a role of TOLs in recognition and further endocytic sorting of a PIN-FORMED
      (PIN)-type auxin carrier protein at the PM, modulating dynamic auxin distribution
      and associated growth responses. Such TOL-dependent vacuolar sorting depends on
      cargo ubiquitination and coincides with dynamic rearrangements in TOL
      distribution. Collectively, these findings lead us to suggest a function for TOLs
      early in the passage of endocytosed ubiquitinated PM cargo, acting as gatekeepers
      for degradative protein sorting to the vacuole.

PMID- 24316204
TI  - Rhythmic sampling within and between objects despite sustained attention at a
      cued location.
AB  - The brain directs its limited processing resources through various selection
      mechanisms, broadly referred to as attention. The present study investigated the
      temporal dynamics of two such selection mechanisms: space- and object-based
      selection. Previous evidence has demonstrated that preferential processing
      resulting from a spatial cue (i.e., space-based selection) spreads to uncued
      locations if those locations are part of the same object (i.e., resulting in
      object-based selection), but little is known about the relationship between these
      fundamental selection mechanisms. Here, we used human behavioral data to
      determine how space- and object-based selection simultaneously evolve under
      conditions that promote sustained attention at a cued location, varying the cue
      to-target interval from 300 to 1100 ms. We tracked visual-target detection at a
      cued location (i.e., space-based selection), at an uncued location that was part
      of the same object (i.e., object-based selection), and at an uncued location that
      was part of a different object (i.e., in the absence of space- and object-based
      selection). The data demonstrate that even under static conditions, there is a
      moment-to-moment reweighting of attentional priorities based on object
      properties. This reweighting is revealed through rhythmic patterns of visual
      target detection both within (at 8 Hz) and between (at 4 Hz) objects. 

PMID- 24316205
TI  - The unfolded protein response in a pair of sensory neurons promotes entry of C.
      elegans into dauer diapause.
AB  - In response to unfavorable environmental conditions such as starvation, crowding,
      and elevated temperature, Caenorhabditis elegans larvae enter an alternative
      developmental stage known as dauer, which is characterized by adaptive changes in
      stress resistance and metabolism. The genetic dissection of the molecular
      mechanisms of the C. elegans dauer developmental decision has defined
      evolutionarily conserved signaling pathways of organismal neuroendocrine
      physiology. Here, we have identified a mechanism by which a dominant mutation in
      a neuronal insulin gene, daf-28(sa191), causes constitutive entry into dauer
      diapause. We demonstrate that expression of the mutant DAF-28 insulin peptide
      results in endoplasmic reticulum (ER) stress in the ASI pair of chemosensory
      neurons. The neuronal ER stress does not compromise cellular survival but
      activates PEK-1, the C. elegans ortholog of the mammalian eIF2alpha kinase PERK,
      which in turn phosphorylates Ser49 of eIF2alpha, specifically in the ASI neuron
      pair, to promote entry into dauer diapause. Our data establish a novel role for
      ER stress and the unfolded protein response (UPR) in promoting entry into dauer
      diapause and suggest that, in addition to cell-autonomous activities in the
      maintenance of ER homeostasis, the UPR may act in a non-cell-autonomous manner to
      promote organismal adaptation to stress during larval development.

PMID- 24316206
TI  - Olfactory preference for egg laying on citrus substrates in Drosophila.
AB  - BACKGROUND: Egg-laying animals, such as insects, ensure the survival of their
      offspring by depositing their eggs in favorable environments. To identify
      suitable oviposition sites, insects, such as the vinegar fly Drosophila
      melanogaster, assess a complex range of features. The fly selectively lays eggs
      in fermenting fruit. However, the precise cues and conditions that trigger
      oviposition remain unclear, including whether flies are also selective for the
      fruit substrate itself. RESULTS: Here, we demonstrate that flies prefer Citrus
      fruits as oviposition substrate. Flies detect terpenes characteristic of these
      fruits via a single class of olfactory sensory neurons, expressing odorant
      receptor Or19a. These neurons are necessary and sufficient for selective
      oviposition. In addition, we find that the Citrus preference is an ancestral
      trait, presumably representing an adaptation toward fruits found within the
      native African habitat. Moreover, we show that endoparasitoid wasps that
      parasitize fly larvae are strongly repelled by the smell of Citrus, as well as by
      valencene, the primary ligand of Or19a. Finally, larvae kept in substrates
      enriched with valencene suffer a reduced risk of parasitism. CONCLUSIONS: Our
      results demonstrate that a single dedicated olfactory pathway determines
      oviposition fruit substrate choice. Moreover, our work suggests that the fly's
      fruit preference--reflected in the functional properties of the identified neuron
      population--stem from a need to escape parasitism from endoparasitoid wasps.

PMID- 24316207
TI  - A differential cargo-loading model of ciliary length regulation by IFT.
AB  - BACKGROUND: During the assembly and maintenance of cilia, precursor proteins need
      to be transported from the cell body into the organelle. Intraflagellar transport
      (IFT) is assumed to be the predominant protein transport pathway in cilia, but it
      remains largely unknown how ciliary proteins use IFT to reach their destination
      sites in the cilium and whether the amount of cargo transported by IFT is
      regulated. RESULTS: Single-particle imaging showed that DRC4, a structural
      protein of the axoneme, moves in association with IFT particles inside
      Chlamydomonas reinhardtii cilia. IFT is required for DRC4 transport both into and
      within the cilium. DRC4 cargoes dissociate from IFT trains at the tip as well as
      at various sites along the length of the cilium. Unloaded DRC4 diffuses before
      docking at its axonemal assembly site. In growing cilia, DRC4 transport by IFT
      was strongly increased over the steady-state level, and the frequency decreased
      linearly with the increasing ciliary length. The frequency of DRC4 transport was
      similarly elevated in short growth-arrested cilia and remained high even when the
      amount of DRC4 available in the cell body was reduced. CONCLUSIONS: DRC4 is a
      bona fide cargo of IFT. Incompletely assembled cilia trigger an increase in the
      amount of DRC4 cargo transported by IFT particles, and DRC4 transport is
      downregulated as cilia approach their steady-state length. We propose a model in
      which ciliary length is controlled by regulating the amount of cargo transported
      by IFT particles.

PMID- 24316208
TI  - Gradual molecular evolution of a sex determination switch through incomplete
      penetrance of femaleness.
AB  - Some genes regulate phenotypes that are either present or absent. They are often
      important regulators of developmental switches and are involved in morphological
      evolution. We have little understanding of the molecular mechanisms by which
      these absence/presence gene functions have evolved, because the phenotype and
      fitness of molecular intermediate forms are unknown. Here, we studied the sex
      determining switch of 14 natural sequence variants of the csd gene among 76
      genotypes of the honeybee (Apis mellifera). Heterozygous genotypes (different
      specificities) of the csd gene determine femaleness, while hemizygous genotypes
      (single specificity) determine maleness. Homozygous genotypes of the csd gene
      (same specificity) are lethal. We found that at least five amino acid differences
      and length variation between Csd specificities in the specifying domain (PSD)
      were sufficient to regularly induce femaleness. We estimated that, on average,
      six pairwise amino acid differences evolved under positive selection. We also
      identified a natural evolutionary intermediate that showed only three amino acid
      length differences in the PSD relative to its parental allele. This genotype
      showed an intermediate fitness because it implemented lethality regularly and
      induced femaleness infrequently (i.e., incomplete penetrance). We suggest
      incomplete penetrance as a mechanism through which new molecular switches can
      gradually and adaptively evolve.

PMID- 24316209
TI  - Cucurbitacin B and cucurbitacin I suppress adipocyte differentiation through
      inhibition of STAT3 signaling.
AB  - Cucurbitacin B, a member of the cucurbitaceae family, can act as a STAT3
      signaling inhibitor to regulate the growth of hepatocellular carcinoma. STAT3
      signaling has been shown to inhibit adipocyte differentiation through C/EBPalpha
      and PPARgamma. Based on these studies, we hypothesized that cucurbitacin B would
      prevent PPARgamma mediated adipocyte differentiation through STAT3 signaling. To
      test this hypothesis, mesenchymal C3H10T1/2 and 3T3-L1 preadipocyte cells were
      treated with a sub-cytotoxic concentration of cucurbitacin B. Cucurbitacin B
      treatment inhibits lipid accumulation and expression of adipocyte markers
      including PPARgamma and its target genes in a dose-dependent manner. Cucurbitacin
      B treatment impairs STAT3 signaling as manifested by reduced phosphorylation of
      STAT3 and suppression of STAT3 target gene expression in preadipocytes. The anti
      adipogenic effects of cucurbitacin B are significantly blunted in cells with
      STAT3 silenced by introducing small interfering RNA. Finally, our data show that
      cucurbitacin I, another cucurbitacin family member, also inhibits adipocyte
      differentiation by suppressing STAT3 signaling. Together, our data suggest the
      possibility of utilizing cucurbitacins as a new strategy to treat metabolic
      diseases and implicate STAT3 as a new target for the development of functional
      foods and drugs.

PMID- 24316210
TI  - Pesticide residues in grain from Kazakhstan and potential health risks associated
      with exposure to detected pesticides.
AB  - This paper presents the first study of pesticide residue results in grain from
      Kazakhstan. A total of 80 samples: barley, oat, rye, and wheat were collected and
      tested in the accredited laboratory. Among 180 pesticides, 10 active substances
      were detected. Banned pesticides, such as DDTs, gamma-HCH, aldrin and diazinon
      were found in cereal grain. Chlorpyrifos methyl and pirimiphos methyl were the
      most frequently detected residues. No residues were found in 77.5% of the
      samples, 13.75% contained pesticide residues at or below MRLs, and 8.75% above
      MRLs. The greatest percentage of samples with residues (29%) was noted for wheat,
      and the lowest for rye (20%). Obtained data were used to estimate potential
      health risks associated with exposure to these pesticides. The highest estimated
      daily intakes (EDIs) were as follows: 789% of the ADI for aldrin (wheat) and
      49.8% of the ADI for pirimiphos methyl (wheat and rye). The acute risk from
      aldrin and tebuconazole in wheat was 315.9% and 98.7% ARfD, respectively. The
      results show that despite the highest EDIs of pesticide residues in cereals, the
      current situation could not be considered a serious public health problem.
      Nevertheless, an investigation into continuous monitoring of pesticide residues
      in grain is recommended. 

PMID- 24316211
TI  - Derivation of safe health-based exposure limits for potential consumer exposure
      to styrene migrating into food from food containers.
AB  - Residual styrene present in polystyrene food packaging may migrate into food at
      low levels. To assure safe use, safe exposure levels are derived for consumers
      potentially exposed via food using No/Low Adverse Effect Levels from animal and
      human studies and assessment factors proposed by European organisations (EFSA,
      ECHA, ECETOC). Ototoxicity and developmental toxicity in rats and human
      ototoxicity and effects on colour discrimination have been identified as the most
      relevant toxicological properties for styrene health assessments. Safe exposure
      levels derived from animal studies with assessment factors of EFSA and ECHA were
      expectedly much lower than those using the ECETOC approach. Comparable safe
      exposure levels were obtained from human data with all sets of assessment factors
      while ototoxicity in rats led to major differences. The safe exposure levels
      finally selected based on criteria of science and health protection converged to
      the range of 90-120 mg/person/d. Assuming a consumption of 1 kg food/d for an
      adult, this translates to 90 mg styrene migration into 1 kg food as safe for
      consumers. This assessment supports a health based Specific Migration Limit of 90
      ppm, a value somewhat higher than the current overall migration limit of 60 ppm
      in the European Union.

PMID- 24316212
TI  - Dietary safety of cycloastragenol from Astragalus spp.: subchronic toxicity and
      genotoxicity studies.
AB  - Extracts, teas, and other preparations of Astragalus roots (e.g., Radix
      Astragali) are historically recognized traditional medicines and foods.
      Cycloastragenol (CAG), a bioactive triterpene aglycone from Astragalus root
      extracts, is being developed as a modern dietary ingredient. To this end, studies
      assessing subchronic toxicity and genotoxic potential were conducted. In the
      subchronic study with recovery component, rats ingested 0, 40, 80, or 150 mg/kg/d
      CAG by oral gavage for ?91 consecutive days. No treatment-related mortalities
      occurred and no cardiac effects were identified. Although several endpoints among
      those monitored (i.e., clinical observations, body weight, food consumption,
      ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ
      weights, or histopathology) exhibited statistically significant effects, none was
      adverse. The oral no-observed-adverse-effect level (NOAEL) for CAG was >150
      mg/kg/d in male and female rats. CAG (?5000 MUg/plate) did not induce
      mutagenicity in Salmonella typhimurium or Escherichia coli tester strains.
      Although the in vitro chromosome aberration assay gave a moderately positive
      response (likely due to poor solubility) for one intermediate concentration
      (1.50mM) with metabolic activation, responses were negative in all other test
      groups. Finally, in the in vivo micronucleus assay no clastogenicity was observed
      in peripheral erythrocytes from mice administered 2000 mg/kg CAG by
      intraperitoneal injection.

PMID- 24316213
TI  - The calmodulin inhibitor and antipsychotic drug trifluoperazine inhibits voltage
      dependent K+ channels in rabbit coronary arterial smooth muscle cells.
AB  - We investigated the effect of the calmodulin inhibitor and antipsychotic drug
      trifluoperazine on voltage-dependent K(+) (Kv) channels. Kv currents were
      recorded by whole-cell configuration of patch clamp in freshly isolated rabbit
      coronary arterial smooth muscle cells. The amplitudes of Kv currents were reduced
      by trifluoperazine in a concentration-dependent manner, with an apparent IC50
      value of 1.58+/-0.48 MUM. The rate constants of association and dissociation by
      trifluoperazine were 3.73+/-0.33 MUM(-1) s(-1) and 5.84+/-1.41 s(-1),
      respectively. Application of trifluoperazine caused a positive shift in the
      activation curve but had no significant effect on the inactivation curve.
      Furthermore, trifluoperazine provoked use-dependent inhibition of the Kv current
      under train pulses (1 or 2 Hz). These findings suggest that trifluoperazine
      interacts with Kv current in a closed state and inhibits Kv current in the open
      state in a time- and use-dependent manner, regardless of its function as a
      calmodulin inhibitor and antipsychotic drug.

PMID- 24316214
TI  - Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells
      from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR
      signaling.
AB  - Patients with age related macular degeneration (AMD) will develop vision loss in
      the center of the visual field. Reactive oxygen species (ROS)-mediated retinal
      pigment epithelium (RPE) cell apoptosis is an important contributor of AMD. In
      this study, we explored the pro-survival effect of alpha-melanocyte stimulating
      hormone (alpha-MSH) on oxidative stressed RPE cells. We found that alpha-MSH
      receptor melanocortin 1 receptor (MC1R) was functionally expressed in primary and
      transformed RPE cells. RPE cells were response to alpha-MSH stimulation. alpha
      MSH activated Akt/mammalian target of rapamycin (mTOR) and Erk1/2 signalings in
      RPE cells, which were inhibited by MC1R siRNA knockdown. alpha-MSH protected RPE
      cells from hydrogen peroxide (H2O2)-induced apoptosis, an effect that was almost
      abolished when MC1R was depleted by siRNA. alpha-MSH-mediated S6K1 activation and
      pro-survival effect against H2O2 was inhibited by Akt inhibitors (perifosine, MK
      2206 and LY294002). Further, mTOR inhibition by rapamycin, or by mTOR siRNA
      knockdown, diminished alpha-MSH's pro-survival effect in RPE cells. Thus, Akt and
      its downstream mTOR signaling mediates alpha-MSH-induced survival in RPE cells.
      In summary, we have identified a new alpha-MSH-MC1R physiologic pathway that
      reduces H2O2-induced RPE cell damage, and might minimize the risk of developing
      AMD.

PMID- 24316215
TI  - N'-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide is a dynamin GTPase
      inhibitor that suppresses cancer cell migration and invasion by inhibiting actin
      polymerization.
AB  - Dynasore, a specific dynamin GTPase inhibitor, suppresses lamellipodia formation
      and cancer cell invasion by destabilizing actin filaments. In search for novel
      dynamin inhibitors that suppress actin dynamics more efficiently, dynasore
      analogues were screened. N'-[4-(dipropylamino)benzylidene]-2
      hydroxybenzohydrazide (DBHA) markedly reduced in vitro actin polymerization, and
      dose-dependently inhibited phosphatidylserine-stimulated dynamin GTPase activity.
      DBHA significantly suppressed both the recruitment of dynamin 2 to the leading
      edge in U2OS cells and ruffle formation in H1299 cells. Furthermore, DBHA
      suppressed both the migration and invasion of H1299 cells by approximately 70%.
      Furthermore, intratumoral DBHA delivery significantly repressed tumor growth.
      DBHA was much less cytotoxic than dynasore. These results strongly suggest that
      DBHA inhibits dynamin-dependent actin polymerization by altering the interactions
      between dynamin and lipid membranes. DBHA and its derivative may be potential
      candidates for potent anti-cancer drugs. 

PMID- 24316216
TI  - Spatial and temporal patterns of pesticide use on California almonds and
      associated risks to the surrounding environment.
AB  - Various stakeholders of California almonds have been investing efforts into
      mitigating pesticide impacts on human and ecosystem health. This study is the
      first comprehensive evaluation that examines the spatial and temporal patterns of
      pesticide use and associated environmental risks. The pesticide use data from
      1996 to 2010 were obtained from the Pesticide Use Reporting database. The
      Pesticide Use Risk Evaluation indicator was employed to evaluate the pesticide
      environmental risks based on the pesticide properties and local environmental
      conditions. Analyses showed that the use intensities (UI) of insecticides (oils
      accounted for 86% of the total insecticide UI) and herbicides both increased from
      north to south; fungicides showed the opposite spatial pattern; and fumigants
      were used most intensively in the middle region. The UI of fungicides and
      herbicides significantly decreased and increased, respectively, throughout the
      study area. The insecticide UI significantly decreased in the north but increased
      in many areas in the south. In particular, the organophosphate UI significantly
      decreased across the study area, while the pyrethroid UI significantly increased
      in the south. The fumigant UI did not show a trend. The regional risk intensities
      of surface water (RIW), soil (RIS), and air (RIA) all increased from north to
      south, while the groundwater regional risk intensity (RIG) decreased from north
      to south. The main trends of RIW, RIG, and RIS were decreasing, while the RIA did
      not show a trend in any region. It's noticeable that although the herbicide UI
      significantly increased, the UI of high-leaching herbicides significantly
      decreased, which led to the significant decrease of RIG. In summary, the temporal
      trends of the pesticide use and risks indicate that the California almond growers
      are making considerable progress towards sustainable pest management via
      integrated pest management, but still require more efforts to curb the fast
      increase of herbicide use. 

PMID- 24316217
TI  - 3D molecular modeling and evolutionary study of the Trypanosoma brucei DNA
      Topoisomerase IB, as a new emerging pharmacological target.
AB  - In the present study, an outline is proposed that may lead to specific drug
      design targeting of the Trypanosoma brucei DNA Topoisomerase IB. In this
      direction, an unequivocally specific platform was designed for the development of
      selective modulators. The designed platform is focused on the unique structural
      and catalytic features of the enzyme. Extensive phylogenetic analysis based on
      all available published genomes indicated a broad distribution of DNA
      topoisomerases across eukaryotic species and revealed structurally important
      amino acids which could be assigned as potentially strong contributors to the
      regulation of the mechanism of the T. brucei DNA Topoisomerase IB. Based on the
      above, we propose a comprehensive in silico 3D model for the structure of the T.
      brucei DNA Topoisomerase IB. Our approach provides an efficient intergraded
      platform with both evolutionary and structural insights for the rational design
      of pharmacophore models as well as novel modulators as the anti-T. brucei DNA
      Topoisomerase IB agents with therapeutic potential. 

PMID- 24316218
TI  - Effect of modality on cardiopulmonary exercise testing in male and female COPD
      patients.
AB  - The purpose of this study was to examine the physiological responses to treadmill
      and cycle cardiopulmonary exercise testing (CPET) in male and female COPD
      patients. Fifty-five patients [28 males (FEV1=58.2+/-19.5% predicted), and 27
      females (FEV1=65.3+/-16.6% predicted)] completed a treadmill and a cycle CPET in
      random order on two separate days. Respiratory and cardiovascular data were
      obtained. Compared to the cycle CPET, the treadmill elicited greater peak power
      output and peak oxygen uptake, while arterial saturation at peak exercise was
      lower with the treadmill; however, there were no differences between the
      responses in men and women. No differences were observed in heart rate,
      ventilation, tidal volume/breathing frequency, inspiratory capacity, or dyspnea
      responses between modalities or sex. The physiological responses between
      treadmill and cycle CPET protocols are largely similar for both men and women
      with COPD, indicating that either modality can be used in mild/moderate COPD
      patients. 

PMID- 24316219
TI  - An open-source software for automatic calculation of respiratory parameters based
      on esophageal pressure.
AB  - PURPOSE: We have developed a software that automatically calculates respiratory
      effort indices, including intrinsic end expiratory pressure (PEEPi) and
      esophageal pressure-time product (PTPeso). MATERIALS AND METHODS: The software
      first identifies respiratory periods. Clean signals are averaged to provide a
      reference mean cycle from which respiratory parameters are extracted. The onset
      of the inspiratory effort is detected automatically by looking backward from the
      onset of inspiratory flow to the first point where the esophageal pressure
      derivative is equal to zero (inflection point). PEEPi is derived from this point.
      Twenty-three recordings from 16 patients were analyzed with the algorithm and
      compared with experts' manual analysis of signals: 15 recordings were performed
      during spontaneous breathing, 1 during non-invasive mechanical ventilation, and 7
      under both conditions. RESULTS: For all values, the coefficients of
      determinations (r(2)) exceeded 0.94 (p<0.001). The bias (mean difference) between
      PEEPi calculated by hand and automatically was -0.26+/-0.52cmH2O during
      spontaneous breathing and the precisions (standard deviations of the differences)
      was 0.52cmH2O with limits of agreement of 0.78 and -1.30cmH2O. The mean
      difference between PTPeso calculated by hand and automatically was -0.38+/
      1.42cmH2Os/cycle with limits of agreement of 2.46 and -3.22cmH2Os/cycle.
      CONCLUSIONS: Our program provides a reliable method for the automatic calculation
      of PEEPi and respiratory effort indices, which may facilitate the use of these
      variables in clinical practice. The software is open source and can be improved
      with the development and validation of new respiratory parameters.

PMID- 24316221
TI  - Conserved RNA helicase FRH acts nonenzymatically to support the intrinsically
      disordered neurospora clock protein FRQ.
AB  - Protein conformation dictates a great deal of protein function. A class of
      naturally unstructured proteins, termed intrinsically disordered proteins (IDPs),
      demonstrates that flexibility in structure can be as important mechanistically as
      rigid structure. At the core of the circadian transcription/translation feedback
      loop in Neurospora crassa is the protein FREQUENCY (FRQ), shown here shown to
      share many characteristics of IDPs. FRQ in turn binds to FREQUENCY-Interacting
      RNA Helicase (FRH), whose clock function has been assumed to relate to its
      predicted helicase function. However, mutational analyses reveal that the
      helicase function of FRH is not essential for the clock, and a region of FRH
      distinct from the helicase region is essential for stabilizing FRQ against rapid
      degradation via a pathway distinct from its typical ubiquitin-mediated turnover.
      These data lead to the hypothesis that FRQ is an IDP and that FRH acts
      nonenzymatically, stabilizing FRQ to enable proper clock circuitry/function.

PMID- 24316220
TI  - DNA double-strand break repair pathway choice is directed by distinct MRE11
      nuclease activities.
AB  - MRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break
      repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease
      activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous
      recombination (HR) remains enigmatic. Here, we employed structure-based design
      with a focused chemical library to discover specific MRE11 endo- or exonuclease
      inhibitors. With these inhibitors, we examined repair pathway choice at DSBs
      generated in G2 following radiation exposure. While nuclease inhibition impairs
      radiation-induced replication protein A (RPA) chromatin binding, suggesting
      diminished resection, the inhibitors surprisingly direct different repair
      outcomes. Endonuclease inhibition promotes NHEJ in lieu of HR, while exonuclease
      inhibition confers a repair defect. Collectively, the results describe nuclease
      specific MRE11 inhibitors, define distinct nuclease roles in DSB repair, and
      support a mechanism whereby MRE11 endonuclease initiates resection, thereby
      licensing HR followed by MRE11 exonuclease and EXO1/BLM bidirectional resection
      toward and away from the DNA end, which commits to HR. 

PMID- 24316222
TI  - Reciprocal regulation of HIF-1alpha and lincRNA-p21 modulates the Warburg effect.
AB  - Hypoxia has long been linked to the Warburg effect, yet the underlying mechanism
      remains largely unclear. It is also not known if lncRNAs are involved in the
      contribution of hypoxia to the Warburg effect. Here we show that lincRNA-p21 is a
      hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis.
      Hypoxia/HIF-1alpha-induced lincRNA-p21 is able to bind HIF-1alpha and VHL and
      thus disrupts the VHL-HIF-1alpha interaction. This disassociation attenuates VHL
      mediated HIF-1alpha ubiquitination and causes HIF-1alpha accumulation. These data
      indicate the existence of a positive feedback loop between HIF-1alpha and lincRNA
      p21 that promotes glycolysis under hypoxia. The ability of lincRNA-p21 to promote
      tumor growth is validated in mouse xenograft models. Together, these findings
      suggest that lincRNA-p21 is an important player in the regulation of the Warburg
      effect and also implicate lincRNA-p21 as a valuable therapeutic target for
      cancer.

PMID- 24316224
TI  - Mineralisation of soft and hard tissues and the stability of biofluids.
AB  - Evidence is provided from studies on natural and artificial biofluids that the
      sequestration of amorphous calcium phosphate by peptides or proteins to form
      nanocluster complexes is of general importance in the control of physiological
      calcification. A naturally occurring mixture of osteopontin peptides was shown,
      by light and neutron scattering, to form calcium phosphate nanoclusters with a
      core-shell structure. In blood serum and stimulated saliva, an invariant calcium
      phosphate ion activity product was found which corresponds closely in form and
      magnitude to the ion activity product observed in solutions of these osteopontin
      nanoclusters. This suggests that types of nanocluster complexes are present in
      these biofluids as well as in milk. Precipitation of amorphous calcium phosphate
      from artificial blood serum, urine and saliva was determined as a function of pH
      and the concentration of osteopontin or casein phosphopeptides. The position of
      the boundary between stability and precipitation was found to agree
      quantitatively with the theory of nanocluster formation. Artificial biofluids
      were prepared that closely matched their natural counterparts in calcium and
      phosphate concentrations, pH, saturation, ionic strength and osmolality. Such
      fluids, stabilised by a low concentration of sequestering phosphopeptides, were
      found to be highly stable and may have a number of beneficial applications in
      medicine. 

PMID- 24316223
TI  - PKM2 regulates chromosome segregation and mitosis progression of tumor cells.
AB  - Tumor-specific pyruvate kinase M2 (PKM2) is instrumental in both aerobic
      glycolysis and gene transcription. PKM2 regulates G1-S phase transition by
      controlling cyclin D1 expression. However, it is not known whether PKM2 directly
      controls cell-cycle progression. We show here that PKM2, but not PKM1, binds to
      the spindle checkpoint protein Bub3 during mitosis and phosphorylates Bub3 at
      Y207. This phosphorylation is required for Bub3-Bub1 complex recruitment to
      kinetochores, where it interacts with Blinkin and is essential for correct
      kinetochore-microtubule attachment, mitotic/spindle-assembly checkpoint, accurate
      chromosome segregation, cell survival and proliferation, and active EGF receptor
      induced brain tumorigenesis. In addition, the level of Bub3 Y207 phosphorylation
      correlated with histone H3-S10 phosphorylation in human glioblastoma specimens
      and with glioblastoma prognosis. These findings highlight the role of PKM2 as a
      protein kinase controlling the fidelity of chromosome segregation, cell-cycle
      progression, and tumorigenesis.

PMID- 24316225
TI  - D-stat culture for studying the metabolic shifts from oxidative metabolism to
      lipid accumulation and citric acid production in Yarrowia lipolytica.
AB  - Lipid accumulation in oleaginous yeasts is triggered by nutrient imbalance in the
      culture medium between the carbon source in excess and the nitrogen source in
      limiting concentration. However Yarrowia lipolytica when cultivated on glucose as
      the sole carbon source, mainly produces citric acid upon nitrogen limitation over
      lipid accumulation (only 5-10% triacylglycerol). Therefore for developing
      bioprocess for the production of triacylglycerol from renewable carbon source as
      glucose it is of first importance to control this imbalance in order to avoid
      citric acid production during TAG accumulation. Using D-stat cultivation system,
      where the N/C was linearly decreased using a constant change rate we were able to
      identify the N/C ratio inducing TAG accumulation (0.085NmolCmol(-1)) and citric
      acid (0.021NmolCmol(-1)). We therefore demonstrated that it was possible to
      accumulate lipids without excretion citric acid as long as the N/C was within
      this indicated range. Moreover enzyme specific activities measurement during the
      D-stat indicated that ATP-citrate lyase, malic enzyme and acetyl-coA carboxylase
      were strongly induced at the onset of lipid accumulation and showed different
      patterns when citric acid was excreted. Our results give relevant information for
      future industrial bioprocess development concerning the production of lipids
      using renewable carbohydrate substrates as an alternative way to produce synthons
      for fuel or chemical industry. By controlling the N/C over the fermentation
      process on glucose Y. lipolytica can accumulate lipids without excreting citric
      acid. 

PMID- 24316226
TI  - Cloning and characterization of canadine synthase involved in noscapine
      biosynthesis in opium poppy.
AB  - Noscapine biosynthesis in opium poppy is thought to occur via N-methylcanadine,
      which would be produced through 9-O-methylation of (S)-scoulerine, methylenedioxy
      bridge formation on (S)-tetrahydrocolumbamine, and N-methylation of (S)-canadine.
      Only scoulerine 9-O-methyltransferase has been functionally characterized. We
      report the isolation and characterization of a cytochrome P450 (CYP719A21) from
      opium poppy that converts (S)-tetrahydrocolumbamine to (S)-canadine. Recombinant
      CYP719A21 displayed strict substrate specificity and high affinity (Km=4.63+/
      0.71 MUM) for (S)-tetrahydrocolumbamine. Virus-induced gene silencing of
      CYP719A21 caused a significant increase in (S)-tetrahydrocolumbamine accumulation
      and a corresponding decrease in the levels of putative downstream intermediates
      and noscapine in opium poppy plants.

PMID- 24316227
TI  - Trk receptors need neutral sphingomyelinase activity to promote cell viability.
AB  - Neurotrophins are a group of secreted polypeptides, which comprises Nerve Growth
      Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Each neurotrophin can
      bind specifically to a tyrosine kinase Trk receptor (TrkA, TrkB or TrkC), while
      all of the neurotrophins can bind, with similar affinity, to the p75 neurotrophin
      receptor (p75(NTR)). Experiments on cell viability promotion by BDNF in granule
      neurons or by NGF in PC12 cells show that neurotrophin-exerted cell viability is
      neutral sphingomyelinase (nSMase)-dependent, since GW4869 or siRNA knockdown
      abrogates the protective effects, as well as neurotrophin-induced Akt
      phosphorylation. Finally, the assessment of nSMase activity promotion drives to
      the conclusion that neurotrophins can promote cell viability through Trk
      receptors in a manner depending on basal nSMase but not through SMase activity
      enhancement. 

PMID- 24316228
TI  - The extreme N-terminal region of human apolipoprotein A-I has a strong propensity
      to form amyloid fibrils.
AB  - The N-terminal 1-83 residues of apolipoprotein A-I (apoA-I) have a strong
      propensity to form amyloid fibrils, in which the 46-59 segment was reported to
      aggregate to form amyloid-like fibrils. In this study, we demonstrated that a
      fragment peptide comprising the extreme N-terminal 1-43 residues strongly forms
      amyloid fibrils with a transition to beta-sheet-rich structure, and that the G26R
      point mutation enhances the fibril formation of this segment. Our results suggest
      that in addition to the 46-59 segment, the extreme N-terminal region plays a
      crucial role in the development of amyloid fibrils by the N-terminal fragment of
      amyloidogenic apoA-I variants. 

PMID- 24316229
TI  - TNF-alpha mediates mitochondrial uncoupling and enhances ROS-dependent cell
      migration via NF-kappaB activation in liver cells.
AB  - Development of hepatocellular carcinoma (HCC) is accompanied by a continuous
      increase in reactive oxygen species (ROS) levels. To investigate the primary
      source of ROS in liver cells, we used tumor necrosis factor-alpha (TNF-alpha) as
      stimulus. Applying inhibitors against the respiratory chain complexes, we
      identified mitochondria as primary source of ROS production. TNF-alpha altered
      mitochondrial integrity by mimicking a mild uncoupling effect in liver cells, as
      indicated by a 40% reduction in membrane potential and ATP depletion (35%). TNF
      alpha-induced ROS production activated NF-kappaB 3.5-fold and subsequently
      enhanced migration up to 12.7-fold. This study identifies complex I and complex
      III of the mitochondrial respiratory chain as point of release of ROS upon TNF
      alpha stimulation of liver cells, which enhances cell migration by activating NF
      kappaB signalling. 

PMID- 24316230
TI  - Characterization of the circulating hemocytes in mud crab (Scylla olivacea)
      revealed phenoloxidase activity.
AB  - This study focused on an isolation and characterization of the circulating
      hemocytes in mud crab, Scylla olivacea. Isolation of specific cell types of
      hemocytes from crab hemolymph was accomplished by using 60% Percoll density
      gradient centrifugation. Four separated bands of the hemocytes were successfully
      obtained. Characterization of these isolated hemocytes by light microscope using
      trypan blue-rose bengal staining, rose bengal-hematoxilin staining, and phase
      contrast revealed four distinct types of hemocyte cells. Using their specific
      morphology and granularity, they were identified as hyaline cell (HC), small
      granular cell (SGC), large granular cell (LGC) and mixed granular cell (MGC).
      Transmission electron microscopy (TEM) revealed more details on specific cell
      size, size of cytoplasmic granule, and nuclear to cytoplasmic ratio, and
      confirmed the classification. Relative abundance of these cells types in the
      hemolymph of an adult crab were 15.50+/-8.22% for HC, 55.50+/-7.15% for SGC,
      13.50+/-5.28% for LGC, and 15.50+/-3.50% for MGC. Proteomic analysis of protein
      expression for each specific cell types by two-dimensional electrophoresis
      identified two highly abundant proteins, prophenoloxidase (ProPO) and
      peroxinectin in LGC. Determination of phenoloxidase (PO) activity in each
      isolated cell types using in vitro and in situ chemical assays confirmed the
      presence of PO activity only in LGC. Based on an increased PO activity of crab
      hemolymph during the course of White Spot Syndrome Virus (WSSV) infection, these
      results suggest that prophenoloxidase pathway was employed for host defense
      mechanism against WSSV and it may link to the role of large granular hemocyte. 

PMID- 24316231
TI  - Follow-up of incidental pulmonary nodules and the radiology report.
AB  - PURPOSE: Incidental pulmonary nodules that require follow-up are often noted on
      chest CT. Evidence-based guidelines regarding appropriate follow-up have been
      published, but the rate of adherence to guideline recommendations is unknown.
      Furthermore, it is unknown whether the radiology report affects the nodule follow
      up rate. METHODS: A review of 1,000 CT pulmonary angiographic studies ordered in
      the emergency department was performed to determine the presence of an incidental
      pulmonary nodule. Fleischner Society guidelines were applied to ascertain if
      follow-up was recommended. Radiology reports were classified on the basis of
      whether nodules were listed in the findings section only, were noted in the
      impression section, or had explicit recommendations for follow-up. Whether the
      rate of nodule follow-up was affected by the radiology report was determined
      according to these 3 groups. RESULTS: Incidental pulmonary nodules that required
      follow-up were noted on 9.9% (95% confidence interval, 8%-12%) of CT pulmonary
      angiographic studies. Follow-up for nodules was poor overall (29% [28 of 96]; 95%
      confidence interval, 20%-38%) and decreased significantly when the nodules were
      mentioned in the findings section only (0% [0 of 12]). Specific instructions to
      follow up nodules in radiology reports still resulted in a low follow-up rate of
      29% (19 of 65; 95% confidence interval, 18%-40%). CONCLUSIONS: Incidental
      pulmonary nodules detected on CT pulmonary angiography are common and are
      frequently not followed up appropriately. Although the inclusion of a pulmonary
      nodule in the impression section of a radiology report is helpful, it does not
      ensure follow-up. Better systems for appropriate identification and follow-up of
      incidental findings are needed.

PMID- 24316232
TI  - ACR appropriateness criteria asymptomatic patient at risk for coronary artery
      disease.
AB  - Atherosclerotic cardiovascular disease is the leading cause of death for both men
      and women in the United States. Coronary artery disease has a long asymptomatic
      latent period and early targeted preventive measures can reduce mortality and
      morbidity. It is important to accurately classify individuals at elevated risk in
      order to identify those who might benefit from early intervention. Imaging
      advances have made it possible to detect subclinical coronary atherosclerosis.
      Coronary artery calcium score correlates closely with overall atherosclerotic
      burden and provides useful prognostic information for patient management. Our
      purpose is to discuss use of diagnostic imaging in asymptomatic patients at
      elevated risk for future cardiovascular events. The goal for these patients is to
      further refine targeted preventative efforts based on risk. The following imaging
      modalities are available for evaluating asymptomatic patients at elevated risk:
      radiography, fluoroscopy, multidetector CT, ultrasound, MRI, cardiac perfusion
      scintigraphy, echocardiography, and PET. The ACR Appropriateness Criteria are
      evidence-based guidelines for specific clinical conditions that are reviewed
      every 2 years by a multidisciplinary expert panel. The guideline development and
      review include an extensive analysis of current medical literature from peer
      reviewed journals and the application of a well-established consensus methodology
      (modified Delphi) to rate the appropriateness of imaging and treatment procedures
      by the panel. In those instances where evidence is lacking or not definitive,
      expert opinion may be used to recommend imaging or treatment. 

PMID- 24316233
TI  - Crouch gait changes after planovalgus foot deformity correction in ambulatory
      children with cerebral palsy.
AB  - Ambulatory children with cerebral palsy (CP) may present with several gait
      patterns due to muscular spasticity, commonly with crouch gait. Several factors
      may contribute to continuous knee flexion during gait, including hamstring and
      gastrocnemius contracture. In planovalgus foot deformity, the combination of heel
      equinus, talonavicular joint dislocation, midfoot break and external tibial
      torsion also contribute to crouch gait as part of lever arm dysfunction. In this
      retrospective cohort study, we assessed 21 children with CP (34 feet) who
      underwent planovalgus foot correction as a single level surgery. Fifteen feet
      underwent subtalar fusion and 19 feet had lateral calcaneal lengthening. Patients
      who underwent knee, hip or pelvis surgeries were excluded from the study. The aim
      was to examine the changes in gait pattern and the correlation between the
      changes of knee flexion at stance phase with the other kinematic and kinetic
      parameters after foot surgery. Post surgery change of Maximum knee extension at
      stance (MKE-dif) was the outcome of interest. The magnitude of change in MKE
      after surgery increased (less crouch after surgery) in patients who had milder
      preoperative planovalgus feet and higher preoperative ankle maximum dorsiflexion
      at stance and ankle power. The gain of knee extension after surgery correlated
      with correction of ankle hyperdorsiflexion and with increase of knee extension at
      initial contact and knee power. Patients with high preoperative ankle maximum
      dorsiflexion may benefit from surgical foot deformity correction to achieve
      decreased ankle dorsiflexion with no knee surgical intervention. 

PMID- 24316234
TI  - Anti-tumor activity of three novel derivatives of ginsenoside on colorectal
      cancer cells.
AB  - 25-Hydroxyprotopanaxadiol (25-OH-PPD) is a natural compound isolated from Panax
      ginseng, and its anti-tumor activity has been studied in previous publication. In
      the current study, we investigated the anti-tumor activity of three novel
      derivatives synthesized from 25-OH-PPD, namely (20R)-12beta-O-(l-chloracetyl)
      dammarane-3beta, 20, 25-triol (xl), (20R)-3beta-O-(l-alanyl)-dammarane-12beta,
      20, 25-triol (1c), and (20R)-3beta-O-(Boc-l-arginyl)-dammarane-12beta, 20, 25
      triol (8b). All three compounds significantly inhibited the growths of human
      colorectal cancer cells, while having lesser effect on the growth of normal
      primary muscle cells and spleno-lymphocytes. Further mechanistic study
      demonstrated that these compounds could induce apoptosis by activating the
      components of caspase-signaling pathways in HCT116 cells, but not in spleno
      lymphocytes. Taken together, the results suggested that 25-OH-PPD derivatives
      exerted promising anti-tumor activity that is specific to human colorectal cancer
      cells, and may therefore represent a potential chemotherapeutic strategy for the
      treatment of colorectal cancer. 

PMID- 24316236
TI  - Bilateral crosstalk of rho- and extracellular-signal-regulated-kinase (ERK)
      pathways is confined to an unidirectional mode in spinal muscular atrophy (SMA).
AB  - Rho-kinase (ROCK) as well as extracellular signal regulated kinase (ERK) control
      actin cytoskeletal organization thereby regulating dynamic changes of cellular
      morphology. In neurons, motility processes such as axonal guidance and neurite
      outgrowth demand a fine regulation of upstream pathways. Here we demonstrate a
      bilateral ROCK-ERK information flow in neurons. This process is shifted towards
      an unidirectional crosstalk in a model of the neurodegenerative disease Spinal
      Muscular Atrophy (SMA), ultimately leading to neurite outgrowth dysregulations.
      As both pathways are of therapeutic relevance for SMA, our results argue for a
      combinatorial ROCK/ERK-targeting as a future treatment strategy. 

PMID- 24316235
TI  - RhoA modulates signaling through the mechanistic target of rapamycin complex 1
      (mTORC1) in mammalian cells.
AB  - The mechanistic target of rapamycin (mTOR) in complex 1 (mTORC1) pathway
      integrates signals generated by hormones and nutrients to control cell growth and
      metabolism. The activation state of mTORC1 is regulated by a variety of GTPases
      including Rheb and Rags. Recently, Rho1, the yeast ortholog of RhoA, was shown to
      interact directly with TORC1 and repress its activation state in yeast. Thus, the
      purpose of the present study was to test the hypothesis that the RhoA GTPase
      modulates signaling through mTORC1 in mammalian cells. In support of this
      hypothesis, exogenous overexpression of either wild type or constitutively active
      (ca)RhoA repressed mTORC1 signaling as assessed by phosphorylation of p70S6K1
      (Thr389), 4E-BP1 (Ser65) and ULK1 (Ser757). Additionally, RhoA.GTP repressed
      phosphorylation of mTORC1-associated mTOR (Ser2481). The RhoA.GTP mediated
      repression of mTORC1 signaling occurred independent of insulin or leucine induced
      stimulation. In contrast to the action of Rho1 in yeast, no evidence was found to
      support a direct interaction of RhoA.GTP with mTORC1. Instead, expression of
      caRheb, but not caRags, was able to rescue the RhoA.GTP mediated repression of
      mTORC1 suggesting RhoA functions upstream of Rheb to repress mTORC1 activity.
      Consistent with this suggestion, RhoA.GTP repressed phosphorylation of TSC2
      (Ser939), PRAS40 (Thr246), Akt (Ser473), and mTORC2-associated mTOR (Ser2481).
      Overall, the results support a model in which RhoA.GTP represses mTORC1 signaling
      upstream of Akt and mTORC2. 

PMID- 24316237
TI  - Effect of temperature and larval density on Aedes polynesiensis (Diptera:
      Culicidae) laboratory rearing productivity and male characteristics.
AB  - Aedes polynesiensis Marks (Diptera: Culicidae) larvae were reared to adulthood in
      the laboratory under a range of temperatures and larval densities. We studied the
      effect of these variables on several life table parameters of relevance to male
      release-based vector control strategies including: larval survivorship,
      developmental time to pupation, male to female ratio, male pupae yield, adult
      male size and survival. The range of tested rearing temperatures (20, 25, 27, and
      30  degrees C) and larval densities (50, 100, 200, and 400 larvae/L) was selected
      within the conditions allowing larval growth and survival. Larval survivorship
      was the highest when larvae were reared at 200 larvae/L for all temperatures
      except 20  degrees C. Male to female ratio was male biased at all temperatures
      and densities. Time to pupation decreased with increasing temperatures. Larval
      density and temperature influenced the proportion of males pupating on first day
      of pupation with 43-47% of total male pupae produced at 25  degrees C. No
      significant differences in mean wing length were observed between male mosquitoes
      reared in the laboratory (except at 20 and 30  degrees C for some densities) and
      field collected males. Altogether, the study allowed the identification of
      rearing conditions delivering high male yield with essentially no female
      contamination, adequate adult male size and survival. Ae. polynesiensis thus
      appears particularly amenable to biological and mechanical sex separation
      offering good prospects for Ae. polynesiensis population suppression trials that
      rely on the production and release of large numbers of incompatible or sterile
      males.

PMID- 24316238
TI  - Cross-linguistic sound symbolism and crossmodal correspondence: Evidence from
      fMRI and DTI.
AB  - Non-arbitrary correspondences between spoken words and categories of meanings
      exist in natural language, with mounting evidence that listeners are sensitive to
      this sound symbolic information. Native English speakers were asked to choose the
      meaning of spoken foreign words from one of four corresponding antonym pairs
      selected from a previously developed multi-language stimulus set containing both
      sound symbolic and non-symbolic stimuli. In behavioral (n=9) and fMRI (n=15)
      experiments, participants showed reliable sensitivity to the sound symbolic
      properties of the stimulus set, selecting the consistent meaning for the sound
      symbolic words at above chances rates. There was increased activation for sound
      symbolic relative to non-symbolic words in left superior parietal cortex, and a
      cluster in left superior longitudinal fasciculus showed a positive correlation
      between fractional anisotropy (FA) and an individual's sensitivity to sound
      symbolism. These findings support the idea that crossmodal correspondences
      underlie sound symbolism in spoken language. 

PMID- 24316239
TI  - Human papillomavirus (HPV) vaccination coverage in young Australian women is
      higher than previously estimated: independent estimates from a nationally
      representative mobile phone survey.
AB  - BACKGROUND: Accurate estimates of coverage are essential for estimating the
      population effectiveness of human papillomavirus (HPV) vaccination. Australia has
      a purpose built National HPV Vaccination Program Register for monitoring
      coverage, however notification of doses administered to young women in the
      community during the national catch-up program (2007-2009) was not compulsory. In
      2011, we undertook a population-based mobile phone survey of young women to
      independently estimate HPV vaccination coverage. METHODS: Randomly generated
      mobile phone numbers were dialed to recruit women aged 22-30 (age eligible for
      HPV vaccination) to complete a computer assisted telephone interview. Consent was
      sought to validate self reported HPV vaccination status against the national
      register. Coverage rates were calculated based on self report and weighted to the
      age and state of residence structure of the Australian female population. These
      were compared with coverage estimates from the register using Australian Bureau
      of Statistics estimated resident populations as the denominator. RESULTS: Among
      the 1379 participants, the national estimate for self reported HPV vaccination
      coverage for doses 1/2/3, respectively, weighted for age and state of residence,
      was 64/59/53%. This compares with coverage of 55/45/32% and 49/40/28% based on
      register records, using 2007 and 2011 population data as the denominators
      respectively. Some significant differences in coverage between the states were
      identified. 20% (223) of women returned a consent form allowing validation of
      doses against the register and provider records: among these women 85.6% (538) of
      self reported doses were confirmed. CONCLUSIONS: We confirmed that coverage rates
      for young women vaccinated in the community (at age 18-26 years) are
      underestimated by the national register and that under-notification is greater
      for second and third doses. Using 2011 population estimates, rather than
      estimates contemporaneous with the program rollout, reduces register-based
      coverage estimates further because of large population increases due to
      immigration since the program.

PMID- 24316241
TI  - The inhibitory effects of silver diamine fluorides on cysteine cathepsins.
AB  - AIM: The expression of cysteine cathepsins in human carious dentine suggests that
      this enzyme contributes to the collagen degradation in caries progress. This
      study investigated whether silver diamine fluoride (SDF) inhibited the activity
      of cysteine cathepsins. METHODS: Three commercial SDF solutions with
      concentrations at 38%, 30% and 12% were studied. Two fluoride solutions with the
      same fluoride ion (F(-)) concentrations as the 38% and 12% SDF solutions, and 2
      silver solutions with the same silver ion (Ag(+)) concentrations as the 38% and
      12% SDF solutions were prepared. Five samples of each experimental solution were
      used to study their inhibitory effect on two cathepsins (B and K) using cathepsin
      assay kits. Positive control contained assay buffer and cathepsins dilution was
      used to calculate the percentage inhibition (difference between the mean readings
      of the test solution and control solution divided by that of the control group).
      RESULTS: The percentage inhibition of 38%, 30% and 12% SDF on cathepsin B were
      92.0%, 91.5% and 90.3%, respectively (p<0.001); on cathepsin K were 80.6%, 78.5%
      and 77.9%, respectively (p<0.001). Ag(+) exhibited the inhibitory effect against
      both cathepsin B and K with or without the presence of F(-) (p<0.01). The
      solutions containing Ag(+) have significantly higher inhibitory effect than the
      solutions containing F(-) only (p<0.01). CONCLUSION: According to this study, SDF
      solution at all 3 tested concentrations significantly inhibited the activity of
      cathepsin B and K.

PMID- 24316242
TI  - Can reading rate acceleration improve error monitoring and cognitive abilities
      underlying reading in adolescents with reading difficulties and in typical
      readers?
AB  - Dyslexia is characterized by slow, inaccurate reading and by deficits in
      executive functions. The deficit in reading is exemplified by impaired error
      monitoring, which can be specifically shown through neuroimaging, in changes in
      Error-/Correct-related negativities (ERN/CRN). The current study aimed to
      investigate whether a reading intervention program (Reading Acceleration Program,
      or RAP) could improve overall reading, as well as error monitoring and other
      cognitive abilities underlying reading, in adolescents with reading difficulties.
      Participants with reading difficulties and typical readers were trained with the
      RAP for 8 weeks. Their reading and error monitoring were characterized both
      behaviorally and electrophysiologically through a lexical decision task.
      Behaviorally, the reading training improved "contextual reading speed" and
      decreased reading errors in both groups. Improvements were also seen in speed of
      processing, memory and visual screening. Electrophysiologically, ERN increased in
      both groups following training, but the increase was significantly greater in the
      participants with reading difficulties. Furthermore, an association between the
      improvement in reading speed and the change in difference between ERN and CRN
      amplitudes following training was seen in participants with reading difficulties.
      These results indicate that improving deficits in error monitoring and speed of
      processing are possible underlying mechanisms of the RAP intervention. We suggest
      that ERN is a good candidate for use as a measurement in evaluating the effect of
      reading training in typical and disabled readers. 

PMID- 24316240
TI  - Fit and Strong! Plus: design of a comparative effectiveness evaluation of a
      weight management program for older adults with osteoarthritis.
AB  - Osteoarthritis (OA) is the most common chronic condition and principal cause of
      disability among older adults. The current obesity epidemic has contributed to
      this high prevalence rate. Fortunately both OA symptoms and obesity can be
      ameliorated through lifestyle modifications. Physical activity (PA) combined with
      weight management improves physical function among obese persons with knee OA but
      evidence-based interventions that combine PA and weight management are limited
      for this population. This paper describes a comparative effectiveness trial
      testing an evidence-based PA program for adults with lower extremity (LE) OA, Fit
      and Strong!, against an enhanced version that also addresses weight management
      based on the evidence-based Obesity Reduction Black Intervention Trial (ORBIT).
      Adult participants (n=400) with LE OA, age 60+, overweight/obese, and not meeting
      PA requirements of >= 150 min per week, are randomized to one of the two
      programs. Both 8-week interventions meet 3 times per week and include 60 min of
      strength, flexibility, and aerobic exercise instruction followed by 30 min of
      education/group discussion. The Fit and Strong! education sessions focus on using
      PA to manage OA; whereas Fit and Strong! Plus addresses PA and weight loss
      management strategies. Maintenance of behavior change is reinforced in both
      groups during months 3-24 through telephone calls and mailed newsletters.
      Outcomes are assessed at baseline, and 2, 6, 12, 18, and 24 months. Primary
      outcomes are dietary change at 2 months followed by weight loss at 6 months that
      is maintained at 24 months. Secondary outcomes assess PA, physical performance,
      and anxiety/depression.

PMID- 24316244
TI  - Retraction notice to "Characterization of a transformed rat retinal ganglion cell
      line" [Brain Res. Mol. Brain Res. 86 (2001) 1-12].

PMID- 24316243
TI  - The protective effect of HET0016 on brain edema and blood-brain barrier
      dysfunction after cerebral ischemia/reperfusion.
AB  - N-hydroxy-N-(4-butyl-2-methylphenyl) formamidine (HET0016) is a specific 20
      hydroxyeicosatetraenoic acid (20-HETE) inhibitor which was first synthesized in
      2001. It has been demonstrated that HET0016 reduces cerebral infarction volume in
      rat middle cerebral artery occlusion (MCAO) models. However, little is known
      about the role of HET0016 in the blood-brain barrier (BBB) dysfunction after
      cerebral ischemia/reperfusion (I/R) injury. The present study was designed to
      examine the effect of HET0016 in a MCAO and reperfusion rat model to determine
      whether it protects against brain edema and BBB disruption. Rats were subjected
      to 90 min MCAO, followed by 4, 24, 48, and 72 h reperfusion. Brain edema was
      measured according to the wet and dry weight method. BBB permeability based on
      the extravasation of Evans blue and sodium fluorescein was detected. BBB
      ultrastructure alterations were presented through transmission electron
      microscope. Superoxide production in ischemic tissue was also measured by
      dihydroethidium fluorescent probe. Western blot was used to analyze the
      expression of Claudin-5, ZO-1, MMP-9, and JNK pathway. At 24h after reperfusion,
      HET0016 reduced brain edema and BBB leakage. Ultrastructural damage of BBB and
      the increase of superoxide production were attenuated by HET0016 treatment.
      Western blot showed that HET0016 suppressed the activation of MMP-9 and JNK
      pathway but restored the expression of Claudin-5 and ZO-1. In conclusion, these
      results suggest that HET0016 protects BBB dysfunction after I/R by regulating the
      expression of MMP-9 and tight junction proteins. Furthermore, inhibition of
      oxidative stress and JNK pathway may be involved in this protecting effect.

PMID- 24316245
TI  - Effects of progesterone on neurite growth inhibitors in the hippocampus following
      global cerebral ischemia.
AB  - In this study, the effects of progesterone (P4) on the immunoreactivity to the
      neurite growth inhibitor Nogo-A, its receptor (Ng-R), and its effector Rho-A in
      the rat hippocampus, in association with parameters of spatial learning and
      memory following global cerebral ischemia, were assessed. Adult male rats were
      subjected to global cerebral ischemia (15 min), and treated with P4 or its
      vehicle at 15 min, 2, 6, 24, 48 and 72 h of reperfusion. Immunoreactivity to Nogo
      A, Ng-R, and Rho-A was evaluated at 24 h, 72 h or 7 d, or at 14 d of reperfusion
      after rats were tested in the Morris Water Maze (MWM). Global cerebral ischemia
      induced an increase in Nogo-A, Ng-R, and Rho-A immunoreactivities in the cell
      bodies of CA1 pyramidal neurons at 24h after global cerebral ischemia, peaking at
      72 h, and persisting 14 d later. In addition, at 72 h, a strong immunoreactivity
      was observed in the hippocampal layers where dendritic arborizations of CA1
      pyramidal neurons are located. Treatment with P4 reduced Nogo-A, Ng-R, and Rho-A
      immunoreactivities in CA1, particularly at 72 h of reperfusion. These effects of
      P4 were consistent with the parameters of a more efficient spatial learning and
      memory in the MWM, as compared to vehicle-treated rats. Overall results suggest
      the reduction of neurite growth inhibitory molecules Nogo-A, Ng-R, and Rho-A, as
      a part of the restorative effects of progesterone possibly allowing the plastic
      phenomena to occur, able to support the functional preservation of the
      hippocampus following global cerebral ischemia.

PMID- 24316246
TI  - Investigation of PAA/PVDF-NZVI hybrids for metronidazole removal: synthesis,
      characterization, and reactivity characteristics.
AB  - For the first time, the removal process of metronidazole (MNZ) from aqueous
      solutions over nano zerovalent iron (NZVI) encapsulated within poly(acrylic acid)
      (PAA)/poly(vinylidene fluoride) (PVDF) membranes was reported. The resultant
      composite (PPN) demonstrated high reactivity, excellent stability and reusability
      over the reaction course. Such excellent performance might be attributed to the
      presence of the charged carboxyl groups in PVDF membrane support, which could
      enhance NZVI dispersion and improve its longevity. Results showed that a lower
      initial concentration and higher reaction temperature facilitated the removal of
      MNZ by PPN, and that the acidic and neutral conditions generally exhibited more
      favorable effect on MNZ removal than the alkaline ones. Kinetics of the MNZ
      removal by PPN was found to follow a two-parameter pseudo-first-order decay model
      well, and the activation energy of the MNZ degradation by PPN was determined to
      be 30.49kJ/mol. The presence of chloride ions slightly enhanced the reactivity of
      PPN with MNZ, whereas sulfate ions inhibited its reactivity. In addition, MNZ
      degradation pathways by PPN were proposed based on the identified intermediates.
      This study suggests that PPN composite possessing excellent performance may be a
      promising functional material to pretreat antibiotic wastewaters. 

PMID- 24316247
TI  - Solvents mediated-synthesis of BiOI photocatalysts with tunable morphologies and
      their visible-light driven photocatalytic performances in removing of arsenic
      from water.
AB  - BiOI photocatalysts with tunable morphologies from 2D laminar structure to 3D
      hierarchitectures have been prepared by a hydrothermal or solvothermal way using
      four kinds of solvents: water, ethanol, ethylene glycol and glycerol (these
      solvents are abbreviated as H2O, ETH, EG, and GLY hereinafter). The viscosity of
      the solvents plays a key role to the evolution on the morphologies and
      performances of BiOI samples. The BiOI synthesized in GLY exhibits excellent
      visible-light photocatalytic performances toward As(III), which is highly
      increased to that of N-TiO2. Further investigation reveals that the surface
      characteristics of BiOI nanosheets, the thickness of the nanosheets, and the way
      by which they integrate together play important roles in photocatalytic reaction
      process. The main active species is detected as O2(-). Considering about the
      practical use, the BiOI synthesized in GLY is also work under illumination of
      natural sunlight, and total arsenic concentration can be decreased even below
      10MUg/L from 1mg/L As(III) aqueous solution within 3h, which has reached the
      drinking water standard (0.01mg/L). Moreover, its stable performance also shows
      its great potential application value in the wastewater treatment. 

PMID- 24316248
TI  - Differential cytotoxic effects of gold nanoparticles in different mammalian cell
      lines.
AB  - Gold nanoparticles (AuNPs) possess unique properties that have been exploited in
      several medical applications. However, a more comprehensive understanding of the
      environmental safety of AuNPs is imperative for use of these nanomaterials. Here,
      we describe the impacts of AuNPs in various mammalian cell models using an
      automatic and dye-free method for continuous monitoring of cell growth based on
      the measurement of cell impedance. Several well-established cytotoxicity assays
      were also used for comparison. AuNPs induced a concentration-dependent decrease
      in cell growth. This inhibitory effect was associated with apoptosis induction in
      Vero cells but not in MRC-5 or NIH3T3 cells. Interestingly, cDNA microarray
      analyses in MRC-5 cells supported the involvement of DNA damage and repair
      responses, cell-cycle regulation, and oxidative stress in AuNP-induced
      cytotoxicity and genotoxicity. Moreover, autophagy appeared to play a role in
      AuNPs-induced attenuation of cell growth in NIH3T3 cells. In this study, we
      present a comprehensive overview of AuNP-induced cytotoxicity in a variety of
      mammalian cell lines, comparing several cytotoxicity assays. Collectively, these
      assays offer convincing evidence of the cytotoxicity of AuNPs and support the
      value of a systematic approach for analyzing the toxicology of nanoparticles. 

PMID- 24316249
TI  - A robust framework to predict mercury speciation in combustion flue gases.
AB  - Mercury emissions from coal combustion have become a global concern as growing
      energy demands have increased the consumption of coal. The effective
      implementation of treatment technologies requires knowledge of mercury speciation
      in the flue gas, namely concentrations of elemental, oxidized and particulate
      mercury at the exit of the boiler. A model that can accurately predict mercury
      species in flue gas would be very useful in that context. Here, a Bayesian
      regularized artificial neural network (BRANN) that uses five coal properties and
      combustion temperature was developed to predict mercury speciation in flue gases
      before treatment technology implementation. The results of the model show that up
      to 97 percent of the variation in mercury species concentration is captured
      through the use of BRANNs. The BRANN model was used to conduct a parametric
      sensitivity which revealed that the coal chlorine content and coal calorific
      value were the most sensitive parameters, followed by the combustion temperature.
      The coal sulfur content was the least important parameter. The results
      demonstrate the applicability of BRANNs for predicting mercury concentration and
      speciation in combustion flue gas and provide a more efficient and effective
      technique when compared to other advanced non-mechanistic modeling strategies. 

PMID- 24316250
TI  - Kinetic characterization of an oxidative, cooperative HMG-CoA reductase from
      Burkholderia cenocepacia.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a key enzyme in
      endogenous cholesterol biosynthesis in mammals and isoprenoid biosynthesis via
      the mevalonate pathway in other eukaryotes, archaea and some eubacteria. In most
      organisms that express this enzyme, it catalyzes the NAD(P)H-dependent reduction
      of HMG-CoA to mevalonate. We have cloned and characterized the 6x-His-tagged HMGR
      from the opportunistic lung pathogen Burkholderia cenocepacia. Kinetic
      characterization shows that the enzyme prefers NAD(H) over NADP(H) as a cofactor,
      suggesting an oxidative physiological role for the enzyme. This hypothesis is
      supported by the fact that the Burkholderia cenocepacia genome lacks the genes
      for the downstream enzymes of the mevalonate pathway. The enzyme exhibits
      positive cooperativity toward the substrates of the reductive reaction, but the
      oxidative reaction exhibits unusual double-saturation kinetics, distinctive among
      characterized HMG-CoA reductases. The unusual kinetics may arise from the
      presence of multiple active oligomeric states, each with different Vmax values. 

PMID- 24316251
TI  - The 1.59A resolution structure of the minor pseudopilin EpsH of Vibrio cholerae
      reveals a long flexible loop.
AB  - The type II secretion complex exports folded proteins from the periplasm to the
      extracellular milieu. It is used by the pathogenic bacterium Vibrio cholerae to
      export several proteins, including its major virulence factor, cholera toxin. The
      pseudopilus is an essential component of the type II secretion system and likely
      acts as a piston to push the folded proteins across the outer membrane through
      the secretin pore. The pseudopilus is composed of the major pseudopilin, EpsG,
      and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. We determined the x-ray
      crystal structure of the head domain of EpsH at 1.59A resolution using molecular
      replacement with the previously reported EpsH structure, 2qv8, as the template.
      Three additional N-terminal amino acids present in our construct prevent an
      artifactual conformation of residues 160-166, present in one of the two monomers
      of the 2qv8 structure. Additional crystal contacts stabilize a long flexible loop
      comprised of residues 104-135 that is more disordered in the 2qv8 structure but
      is partially observed in our structure in very different positions for the two
      EpsH monomers in the asymmetric unit. In one of the conformations the loop is
      highly extended. Modeling suggests the highly charged loop is capable of
      contacting EpsG and possibly secreted protein substrates, suggesting a role in
      specificity of pseudopilus assembly or secretion function. 

PMID- 24316252
TI  - Crystal structure and biochemical characterization of a manganese superoxide
      dismutase from Chaetomium thermophilum.
AB  - A manganese superoxide dismutase from the thermophilic fungus Chaetomium
      thermophilum (CtMnSOD) was expressed in Pichia pastoris and purified to
      homogeneity. Its optimal temperature was 60 degrees C with approximately 75% of
      its activity retained after incubation at 70 degrees C for 60min. Recombinant
      yeast cells carrying C. thermophilum mnsod gene exhibited higher stress
      resistance to salt and oxidative stress-inducing agents than control yeast cells.
      In an effort to provide structural insights, CtMnSOD was crystallized and its
      structure was determined at 2.0A resolution. The overall architecture of CtMnSOD
      was found similar to other MnSODs with highest structural similarities obtained
      against a MnSOD from the thermotolerant fungus Aspergillus fumigatus. In order to
      explain its thermostability, structural and sequence analysis of CtMnSOD with
      other MnSODs was carried out. An increased number of charged residues and an
      increase in the number of intersubunit salt bridges and the Thr:Ser ratio were
      identified as potential reasons for the thermostability of CtMnSOD. 

PMID- 24316253
TI  - Potentiation of macrophage activity by thymol through augmenting phagocytosis.
AB  - The potent role of thymol, a natural compound, in modulation of macrophage
      activity was evaluated by determining all the sequential steps involved during
      phagocytosis. We found a significant increase in the proliferation of splenocytes
      in the presence of thymol and it proved to be a good mitogen. Uptake capacity of
      macrophages was enhanced due to increased membrane fluidity after treatment with
      thymol and it also increases lysosomal activity of macrophages. Data of
      superoxide anion generation revealed the involvement of thymol in the generation
      of respiratory burst as it potentiated this property of macrophages at a
      concentration of 150 MUM. In the case of TNF-alpha, IL-1beta and PGE(2) a
      decreased level of secretion was observed 154 rhog/ml, 736.1 rhog/ml, and 151
      rhog/ml respectively when compared with lipopolysaccharide treated cells, where
      the level of these cytokines was significantly high. We also determined the anti
      complementary activity of thymol which showed to be more effective than
      rosmarinic acid. Thus, the results obtained from the study suggest the potential
      role of thymol as a natural immunostimulatory drug which can be used in the
      treatment of various immunological disorders.

PMID- 24316254
TI  - A novel polysaccharide from the seeds of Plantago asiatica L. induces dendritic
      cells maturation through toll-like receptor 4.
AB  - In this study, we investigated the effect of a polysaccharide purified from the
      seeds of Plantago asiatica L. (PLP-2) on the phenotypic and functional maturation
      of murine bone marrow-derived dendritic cells (DCs) and relevant mechanisms. The
      results showed that PLP-2 increased the expression of maturation markers major
      histocompatibility complex II, CD86, CD80, and CD40 on DCs. Consistent with the
      changes in the phenotypic markers, functional assay for DCs maturation showed
      that PLP-2 decreased DCs endocytosis and increased intracellular interleukin (IL)
      12 levels and allostimulatory activity. Furthermore, using a syngeneic T cell
      activation model, we found that PLP-2 treated DCs presented ovalbumin antigen to
      T cells more efficiently as demonstrated by increased T cell proliferation. In
      addition, the effects of PLP-2 on DCs were significantly impaired by treating the
      cells with anti-TLR4 antibody prior to PLP-2 treatment, implying direct
      interaction between PLP-2 and TLR4 on cell surface. These results suggested that
      PLP-2 may induce DCs maturation through TLR4. Our results may have important
      implications for our understanding on the molecular mechanisms of
      immunopotentiating action of the polysaccharides from plants. 

PMID- 24316255
TI  - Cladribine exerts an immunomodulatory effect on human and murine dendritic cells.
AB  - Cladribine is a purine nucleoside analog developed to treat lymphoid
      malignancies. Reported therapeutic benefits for the autoimmune disease multiple
      sclerosis indicate additional immunomodulatory effects beyond the well
      characterized cytotoxic activity causing lymphopenia. Here, we demonstrate that
      cladribine reduces the secretion of inflammatory cytokines and chemokines by
      murine and human dendritic cells, the most potent antigen-presenting cells. This
      compound also modulates the expression of the activation markers CD86 and MHC II.
      Furthermore, cladribine affects the T cell priming capacity of dendritic cells,
      resulting in reduced induction of interferon-gamma- and tumor necrosis factor
      alpha-producing T cells and increased induction of interleukin-10-producing T
      cells. These effects, observed at cladribine concentrations in the
      therapeutically relevant range of serum steady-state concentrations for leukemia
      and multiple sclerosis, confirm the immunomodulatory activity of cladribine. 

PMID- 24316256
TI  - LPS potentiates nucleotide-induced inflammatory gene expression in macrophages
      via the upregulation of P2Y2 receptor.
AB  - Sepsis is a severe systemic inflammatory response that is associated with high
      morbidity and mortality. A previous study using an animal model of sepsis showed
      that survival was significantly lower in WT mice than in P2Y(2) receptor
      (P2Y(2)R)-deficient mice, suggesting that P2Y(2)R plays a role in septic death.
      We therefore investigated the role of P2Y(2)R in the inflammatory responses of
      RAW264.7 murine macrophages to LPS. LPS time-dependently upregulated P2Y(2)R mRNA
      levels, with a prominent increase observed at 4 h. In addition, LPS increased ATP
      release in a time dependent manner (5-120 min post LPS treatment). Accordingly,
      we pretreated cells with LPS for 4 h to induce P2Y(2)R expression and then
      stimulated the cells with UTP or ATP for 16 h. Interestingly, ATP- or UTP
      dependent P2Y(2)R activation in LPS-pretreated cells resulted in dramatically
      enhanced HMGB1 secretion, COX-2 and iNOS expression, and furthermore PGE2 and NO
      production compared to LPS treatment alone (4 h) or ATP or UTP treatment alone
      (16 h), an effect that was inhibited by P2Y(2)R silencing. In addition, these
      increases in HMGB1 secretion, COX-2 and iNOS expression and PGE(2) and NO
      production commonly involved the JNK, PKC and PDK pathways. Taken together, these
      data demonstrate that LPS-dependent upregulation of P2Y(2)R plays a critical role
      in facilitating the inflammatory responses induced by LPS.

PMID- 24316257
TI  - Echocardiographic nomograms for ventricular, valvular and arterial dimensions in
      caucasian children with a special focus on neonates, infants and toddlers.
AB  - BACKGROUND: A quantitative echocardiographic assessment is often essential for
      the management of congenital heart disease, especially in the first months of
      life. Despite this, pediatric echocardiographic nomograms are limited and
      heterogeneous, particularly for neonates and infants. The aim of this study was
      to establish reliable echocardiographic nomograms in a broad population of
      healthy Caucasian children. METHODS: Two-dimensional and M-mode measurements of
      22 cardiovascular structures were performed. Models using linear, logarithmic,
      exponential, and square root relationships were tested. Heteroscedasticity was
      tested using the White and Breusch-Pagan tests. Age, weight, height, and body
      surface area (BSA; calculated using seven different formulas) were used as the
      independent variables in different analyses to predict the mean value of each
      echocardiographic measurement. Structured Z scores were then computed. RESULTS: A
      total of 445 consecutive Caucasian Italian healthy subjects (age range, 0 days to
      36 months; 49% female subjects) with BSAs ranging from 0.12 to 0.67 m(2) were
      prospectively enrolled. The calculation of BSA using the Haycock formula provided
      the best results, while other formulas either underestimated (DuBois, Mosteller,
      Dreyer, and Meban) or overestimated (Boyd and Gehan) BSA. The Haycock formula has
      been used when presenting data as predicted values (mean +/- 2 SDs) for a given
      BSA and within equations relating echocardiographic measurements to BSA. For all
      the measurements, there was no significant intraobserver or interobserver
      variability. CONCLUSIONS: The investigators report new, reliable
      echocardiographic Z scores derived from a large population of Caucasian neonates,
      infants, and toddlers calculated using a rigorous statistical design. These
      nomograms represent a valid diagnostic tool for echocardiographic quantification
      in this age group.

PMID- 24316258
TI  - Interleukin-18 null mutation increases weight and food intake and reduces energy
      expenditure and lipid substrate utilization in high-fat diet fed mice.
AB  - OBJECTIVE: The proinflammatory cytokine interleukin-18 (IL-18) putatively
      modulates food intake and energy metabolism, but the effects of IL-18 in high-fat
      diet fed animals are unknown. Whether IL-18 alters basal metabolic rate or
      metabolic processes of living is unknown. Here, we tested the hypothesis that IL
      18 modulates weight gain, energy intake, whole-body energy expenditure, and
      utilization of lipid as a fuel substrate in high-fat diet fed mice. METHODS: Food
      intake, whole-body metabolism, and motor activity of IL-18 knockout mice were
      compared to those of wildtype littermates; anorectic effects of
      intracerebroventricular IL-18 administration were compared between IL-18 receptor
      knockout, IL-18/IL-18R knockout and wildtype mice. RESULTS: Chow-reared IL-18
      knockout mice were overweight at 6 months of age and then gained excess weight on
      both low-fat and high-fat diets, ate more high-fat diet, and showed reduced whole
      body energy expenditure and increased respiratory exchange ratios. Reductions in
      energy expenditure of IL-18 knockout mice were seen across fasting vs. feeding
      conditions, low- vs. high-fat diets, high vs. low levels of physical activity and
      times of day, suggesting actions on basal metabolic rate. The circadian amplitude
      of energy expenditure, but not respiratory exchange ratio, food intake, or motor
      activity, also was blunted in IL-18 knockout mice. Central IL-18 administration
      reduced high-fat diet intake in wildtype mice, but not in mice lacking the IL-18
      receptor. CONCLUSION: The loss-of-function results support the hypothesis that
      endogenous IL-18 suppresses appetite and promote energy expenditure and lipid
      fuel substrate utilization not only during sickness, but also in healthy adults
      consuming high-fat diets.

PMID- 24316259
TI  - Artemisinins: pharmacological actions beyond anti-malarial.
AB  - Artemisinins are a family of sesquiterpene trioxane lactone anti-malarial agents
      originally derived from Artemisia annua L. The anti-malarial action of
      artemisinins involves the formation of free radicals via cleavage of the
      endoperoxide bond in its structure, which mediate eradication of the Plasmodium
      species. With its established safety record in millions of malarial patients,
      artemisinins are also being investigated in diseases like infections, cancers and
      inflammation. Artemisinins have been reported to possess robust inhibitory
      effects against viruses (e.g. Human cytomegalovirus), protozoa (e.g. Toxoplasma
      gondii), helminths (e.g. Schistosoma species and Fasciola hepatica) and fungi
      (e.g. Cryptococcus neoformans). Artemisinins have demonstrated cytotoxic effects
      against a variety of cancer cells by inducing cell cycle arrest, promoting
      apoptosis, preventing angiogenesis, and abrogating cancer invasion and
      metastasis. Artemisinins have been evaluated in animal models of autoimmune
      diseases, allergic disorders and septic inflammation. The anti-inflammatory
      effects of artemisinins have been attributed to the inhibition of Toll-like
      receptors, Syk tyrosine kinase, phospholipase Cgamma, PI3K/Akt, MAPK, STAT-1/3/5,
      NF-kappaB, Sp1 and Nrf2/ARE signaling pathways. This review provides a
      comprehensive update on non-malarial use of artemisinins, modes of action of
      artemisinins in different disease conditions, and drug development of
      artemisinins beyond anti-malarial. With the concerted efforts in the novel
      synthesis of artemisinin analogs and clinical pharmacology of artemisinins, it is
      likely that artemisinin drugs will become a major armamentarium combating a
      variety of human diseases beyond malaria. 

PMID- 24316260
TI  - Increased de novo lipogenesis is a distinct characteristic of individuals with
      nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: There have been few studies of the role of de novo lipogenesis
      in the development of nonalcoholic fatty liver disease (NAFLD). We used isotope
      analyses to compare de novo lipogenesis and fatty acid flux between subjects with
      NAFLD and those without, matched for metabolic factors (controls). METHODS: We
      studied subjects with metabolic syndrome and/or levels of alanine
      aminotransferase and aspartate aminotransferase >30 mU/L, using magnetic
      resonance spectroscopy to identify those with high levels (HighLF, n = 13) or low
      levels (LowLF, n = 11) of liver fat. Clinical and demographic information was
      collected from all participants, and insulin sensitivity was measured using the
      insulin-modified intravenous glucose tolerance test. Stable isotopes were
      administered and gas chromatography with mass spectrometry was used to analyze
      free (nonesterified) fatty acid (FFA) and triacylglycerol flux and lipogenesis.
      RESULTS: Subjects with HighLF (18.4% +/- 3.6%) had higher plasma levels of FFAs
      during the nighttime and higher concentrations of insulin than subjects with
      LowLF (3.1% +/- 2.7%; P = .04 and P < .001, respectively). No differences were
      observed between groups in adipose flux of FFAs (414 +/- 195 MUmol/min for HighLF
      vs 358 +/- 105 MUmol/min for LowLF; P = .41) or production of very-low-density
      lipoprotein triacylglycerol from FFAs (4.06 +/- 2.57 MUmol/min vs 4.34 +/- 1.82
      MUmol/min; P = .77). In contrast, subjects with HighLF had more than 3-fold
      higher rates of de novo fatty acid synthesis than subjects with LowLF (2.57 +/-
      1.53 MUmol/min vs 0.78 +/- 0.42 MUmol/min; P = .001). As a percentage of
      triacylglycerol palmitate, de novo lipogenesis was 2-fold higher in subjects with
      HighLF (23.2% +/- 7.9% vs 10.1% +/- 6.7%; P < .001); this level was independently
      associated with the level of intrahepatic triacylglycerol (r = 0.53; P = .007).
      CONCLUSIONS: By administering isotopes to subjects with NAFLD and control
      subjects, we confirmed that those with NAFLD have increased synthesis of fatty
      acids. Subjects with NAFLD also had higher nocturnal plasma levels of FFAs and
      did not suppress the contribution from de novo lipogenesis on fasting. These
      findings indicate that lipogenesis might be a therapeutic target for NAFLD.

PMID- 24316261
TI  - Distinct cellular origins for serotonin-expressing and enterochromaffin-like
      cells in the gastric corpus.
AB  - BACKGROUND & AIMS: The alimentary tract contains a diffuse endocrine system
      comprising enteroendocrine cells that secrete peptides or biogenic amines to
      regulate digestion, insulin secretion, food intake, and energy homeostasis.
      Lineage analysis in the stomach revealed that a significant fraction of endocrine
      cells in the gastric corpus did not arise from Neurogenin3 (Neurog3)-expressing
      cells, unlike enteroendocrine cells elsewhere in the digestive tract. We aimed to
      isolate enriched serotonin-secreting and enterochromaffin-like (ECL) cells from
      the stomach and to clarify their cellular origin. METHODS: We used Neurogenic
      differentiation 1 (NeuroD1) and Neurog3 lineage analysis and examined the
      differentiation of serotonin-producing and ECL cells in stomach tissues of
      NeuroD1-cre;ROSA(tdTom), tryptophan hydroxylase 1 (Tph1)-cyan fluorescent protein
      (CFP), c-Kit(wsh/wsh), and Neurog3Cre;ROSA(tdTom) mice by immunohistochemistry.
      We used fluorescence-activated cell sorting to isolate each cell type for gene
      expression analysis. We also performed RNA sequencing analysis of ECL cells.
      RESULTS: Neither serotonin-secreting nor ECL cells of the corpus arose from cells
      expressing NeuroD1. Serotonin-secreting cells expressed a number of mast cell
      genes but not genes associated with endocrine differentiation; they did not
      develop in c-Kit(wsh/wsh) mice and were labeled with transplanted bone marrow
      cells. RNA sequencing analysis of ECL cells revealed high expression levels of
      many genes common to endocrine cells, including transcription factors, hormones,
      ion channels, and solute transporters but not markers of bone marrow cells.
      CONCLUSIONS: Serotonin-expressing cells of the gastric corpus of mice appear to
      be bone marrow-derived mucosal mast cells. Gene expression analysis of ECL cells
      indicated that they are endocrine cells of epithelial origin that do not express
      the same transcription factors as their intestinal enteroendocrine cell
      counterparts.

PMID- 24316262
TI  - Telaprevir twice daily is noninferior to telaprevir every 8 hours for patients
      with chronic hepatitis C.
AB  - BACKGROUND & AIMS: We performed an open-label, multicenter, phase 3 study of the
      safety and efficacy of twice-daily telaprevir in treatment-naive patients with
      chronic hepatitis C virus (HCV) genotype 1 infection, including those with
      cirrhosis. METHODS: Patients were randomly assigned to groups treated with
      telaprevir 1125 mg twice daily or 750 mg every 8 hours plus peginterferon alfa-2a
      and ribavirin for 12 weeks; patients were then treated with peginterferon alfa-2a
      and ribavirin alone for 12 weeks if their level of HCV RNA at week 4 was <25
      IU/mL or for 36 weeks if their level was higher. The primary objective was to
      demonstrate noninferiority of telaprevir twice daily versus every 8 hours in
      producing a sustained virological response 12 weeks after the end of therapy
      (SVR12) (based on a -11% lower limit of the 95% lower confidence interval for the
      difference between groups). RESULTS: At baseline, of 740 patients, 85% had levels
      of HCV RNA >=800,000 IU/mL, 28% had fibrosis (F3-F4), 14% had cirrhosis (F4), 57%
      were infected with HCV genotype 1a, and 71% had the non-CC IL28B genotype. Of
      patients who were treated with telaprevir twice daily, 74.3% achieved SVR12
      compared with 72.8% of patients who were treated with telaprevir every 8 hours
      (difference in response, 1.5%; 95% confidence interval, -4.9% to 12.0%), so
      telaprevir twice daily is noninferior to telaprevir every 8 hours. All subgroups
      of patients who were treated with telaprevir twice daily versus those who were
      treated every 8 hours had similar rates of SVR12. The most frequent adverse
      events (AEs) in the telaprevir phase were fatigue (47%), pruritus (43%), anemia
      (42%), nausea (37%), rash (35%), and headache (26%); serious AEs were reported in
      9% of patients. Rates of AEs and serious AEs were similar or slightly higher
      among patients treated with telaprevir every 8 hours. CONCLUSIONS: Based on a
      phase 3 trial, telaprevir twice daily is noninferior to every 8 hours in
      producing SVR12, with similar levels of safety and tolerability. These results
      support use of telaprevir twice daily in patients with chronic HCV genotype 1
      infection, including those with cirrhosis. ClinicalTrials.gov, Number:
      NCT01241760.

PMID- 24316263
TI  - Lower endoscopy reduces colorectal cancer incidence in older individuals.
AB  - BACKGROUND & AIMS: In older individuals, there are unclear effects of lower
      endoscopy on incidence of colorectal cancer (CRC) and of colonoscopy on site of
      CRC. We investigated whether sigmoidoscopy or colonoscopy is associated with a
      decreased incidence of CRC in older individuals, and whether the effect of
      colonoscopy differs by anatomic location. METHODS: We performed a case-control
      study using linked US Veterans Affairs and Medicare data. Cases were veterans
      aged 75 years or older diagnosed with CRC in fiscal year 2007. Cases were matched
      for age and sex to 3 individuals without a CRC diagnosis (controls). We
      determined the number of cases and controls who received colonoscopies or
      sigmoidoscopies from fiscal year 1997 to a date 6 months before the diagnosis of
      CRC (for cases) or to a corresponding index date (for controls). The probability
      of exposure was modeled using generalized linear mixed equations, adjusted for
      potential confounders. For the analysis of CRC risk in different anatomic
      locations, the proximal colon was defined as proximal to the splenic flexure.
      RESULTS: We identified 623 cases and 1869 controls (mean age, 81 y; 98.7% male,
      86.2% Caucasian). Among cases, 243 (39.0%) underwent any lower endoscopy (177
      colonoscopies). Among controls, 978 (52.3%) underwent any lower endoscopy (758
      colonoscopies). Cases were significantly less likely than controls to have
      undergone lower endoscopy within the preceding 10 years (adjusted odds ratio
      [aOR], 0.58; 95% confidence interval [CI], 0.48-0.69). This effect was
      significant for colonoscopy (aOR, 0.57; 95% CI, 0.47-0.70), but not
      sigmoidoscopy. Similar results were observed when a 5-year exposure window was
      applied. Colonoscopy was associated with a reduced risk of distal CRC (aOR, 0.45;
      95% CI, 0.32-0.62) and proximal CRC (aOR, 0.65; 95% CI, 0.46-0.92). CONCLUSIONS:
      In a study of the US Veterans Affairs and Medicare databases, lower endoscopy in
      the preceding 10 years was associated with a significant reduction in CRC
      incidence among older veterans. Colonoscopy was associated with significant
      reductions in distal and proximal CRC.

PMID- 24316264
TI  - Spontaneous regression of herniated lumbar discs.
AB  - The spontaneous regression of a lumbar herniated disc is a common occurrence.
      Studies using imaging techniques as well as immunohistologic analyses have
      attempted to explain the mechanism for regression. However, the exact mechanism
      remains elusive. Understanding the process by which herniated discs disappear in
      the absence of surgery may better guide treatment. Recent case reports,
      radiographic and immunohistologic studies show that the extent of extrusion of
      the nucleus pulposus is related to a higher likelihood of regression. To our
      knowledge, Patient 3 is the first report of spontaneous regression occurring
      within 2 months. This occurrence was discovered intraoperatively. We present
      three illustrative patients. Patient 1, a 53-year-old man, presented with a large
      L2-L3 disc herniation. His 2 year follow-up MRI revealed a complete regression of
      the extruded fragment. Patient 2, a 58-year-old man, presented with an L3-L4 disc
      herniation with cephalad migration of a free fragment. MRI 9 months later showed
      no free fragment but progression of a disc bulge. Intraoperative exploration
      during the L3-L4 microdiscectomy confirmed the absence of the free fragment.
      Patient 3, a 58-year-old woman, presented with a large L2-L3 disc extrusion with
      cephalad migration. An imaging study performed 2 months after the initial study
      revealed an absence of the free fragment. Our case reports demonstrate the
      temporal variance in disc regression. While the time course and extent of
      regression vary widely, the rapid time in which regression can occur should
      caution surgeons contemplating discectomy based on an MRI performed a significant
      period prior to surgery.

PMID- 24316265
TI  - A study of microemulsions as prolonged-release injectables through in-situ phase
      transition.
AB  - Microemulsions (MEs) have been studied extensively as colloidal carriers for the
      delivery of both water-soluble and lipid-soluble drugs. Our previous study showed
      that addition of water to ME formulations resulted in phase transition to either
      liquid crystal (LC) or coarse emulsion (CE). The aim of this study was to
      investigate whether these MEs could be used as drug delivery vehicles for
      prolonged release through in-situ phase transition following extravascular
      injection. Three ME formulations from the same pseudo-ternary phase diagram were
      investigated with respect to their phase transition behavior, and in-vivo drug
      release; a coarse emulsion-forming ME (CE-ME), an oil rich LC-forming ME (LC
      ME1), and an oil poor LC-forming ME (LC-ME2). CE-ME was a W/O ME and both LC-MEs
      were O/W type. The release profiles of (99m)Tc labeled MEs following subcutaneous
      (SC) injection in rabbits were investigated with gamma-scintigraphy. The CE-ME
      dispersed readily in water, forming a CE, whereas the LC-forming MEs formed
      'depots' in water. Polarized microscopy revealed a LC boundary spontaneously
      formed at the water/ME interface for the LC-MEs with the LC-ME2 forming a
      substantially thicker LC layer. The CE resulting from the water-induced
      transition of the CE-forming ME had a higher viscosity than the MEs, but lower
      than the LCs resulted from LC-MEs. Compared to LC-ME1, LC-ME2 underwent more
      rapid phase transition and the resultant LC had significant higher viscosity. The
      LCs formed from both ME formulations exhibited pseudoplastic properties;
      increasing the shear rate decreased the apparent viscosity exponentially.
      Following SC injection into the animal thigh, the LC-MEs had more prolonged
      release of (99m)Tc in a first-order manner, than CE-ME. The oil poor LC-ME2 had
      the slowest release with a t1/2 of 77min, 2.3 times longer than the oil rich LC
      ME1; consistent with the thickness of LC layer formation observed in-vitro and
      their relative viscosities. In conclusion, the present in-vivo study has
      demonstrated the application of MEs as extravascular injectable drug delivery
      systems for sustained release. The retention of the vehicles at the injection
      site and the release rate were determined predominantly by their phase transition
      rather than ME type or oil content. 

PMID- 24316266
TI  - Cardiac involvement and its complications about three cases of severe scorpion
      envenomation.
AB  - For several decades, Morocco is confronted to medico-social problem of scorpion
      stings and envenomations. In 2009, epidemiological data established by the Poison
      Control Center recorded 29,816 stung patients, with an incidence of 1.10/00 and a
      fatality rate of 0.18%. The neurotoxins from scorpion venom are potent activators
      of the autonomic nervous system resulting a physiopathological disorder of vital
      systems. The most serious clinical manifestations are neurotoxic effects,
      pulmonary edema and cardiovascular distress. This present work reports the cases
      of three children (4 years and 6 months, 8 months and 15 days, 4 years),
      hospitalized in intensive care for an envenomation by Androctonus mauritanicus
      (the most fatal scorpion specie). The children presented cardiac dysfunction
      where pulmonary edema and state of shock were complications resultants. Two cases
      survived after supportive and symptomatic treatment based on dobutamine as
      primordial treatment in cardiovascular and pulmonary correction and other drugs.
      The third case died. The objective of this work was to detect the limit of the
      effectiveness of symptomatic treatment during a severe scorpion envenomation. 

PMID- 24316267
TI  - Cumulative effects of exposure to cyanobacteria bloom extracts and benzo[a]pyrene
      on antioxidant defence biomarkers in Gammarus oceanicus (Crustacea: Amphipoda).
AB  - The Baltic Sea suffers from extensive blooms of the toxic cyanobacteria Nodularia
      spumigena that produces nodularin toxin (NOD). Additionally, intensification of
      oil transportation and related activities in the area increase the risk of oil
      spills. The current experiment was designed to mimic a situation where an oil
      spill occurs during a cyanobacterial bloom by exposing the amphipod Gammarus
      oceanicus to a NOD-rich cyanobacterial extract and the polycyclic aromatic
      hydrocarbon compound benzo[a]pyrene (B[a]P), a common constituent of oil. The
      activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione
      peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were examined
      after 48 and 96 h of exposure. Exposure to low and high levels of the NOD-rich
      extract produced a time-dependent activation of GST, GPx and SOD. CAT levels were
      elevated only by high NOD treatment. Also the toxicity of B[a]P was indicated by
      significantly elevated antioxidant response. In the combined exposures treatment
      dependent additive increases in the activity of GPx and SOD were observed as well
      as inhibitory (antagonistic) effects on GST, CAT and GPx. Rapid concentration
      dependent accumulation of NOD by G. oceanicus was observed. The addition of B[a]P
      reduced the accumulation of NOD and resulted in different biomarker response
      patterns compared to single exposures demonstrating the effects of mixture
      toxicity.

PMID- 24316268
TI  - Reply: To PMID 24184339.

PMID- 24316269
TI  - Interventions at home births.

PMID- 24316270
TI  - The maternal health clinic: an initiative for cardiovascular risk identification
      in women with pregnancy-related complications.
AB  - OBJECTIVE: Women who develop certain common pregnancy complications have a
      greater chance of developing cardiovascular disease (CVD) later in life. However,
      most health care providers do not provide postpartum cardiovascular risk
      counselling or follow-up. The Maternal Health Clinic was established to address
      this gap in care. It targets women at increased risk of CVD to inspire lifestyle
      changes, encourage long-term follow-up, and initiate primary prevention. Here, we
      summarize results from the first 17 months of completed clinic visits. STUDY
      DESIGN: Patients experiencing at least one relevant complication in their index
      pregnancy were referred to the Maternal Health Clinic through standard postpartum
      order sheets. Patients underwent a complete assessment including screening
      history, physical examination, fasting bloodwork, and urinalysis. Lifetime and 30
      year CVD risk estimates, along with a metabolic syndrome calculation, were
      determined for each patient. RESULTS: Complications most commonly leading to
      referral were gestational diabetes or impaired glucose tolerance (32.7%),
      preeclampsia (29.3%), preterm birth (29.3%), and gestational hypertension
      (19.6%). The clinic analysis group (n = 92) was compared with a healthy control
      group from the PreEclampsia New Emerging Team study (n = 118). Patients in the
      clinic analysis group had significantly increased lifetime and 30-year CVD risk
      estimates compared with healthy controls (P < .0001). Furthermore, 17.4% of the
      clinic analysis group had metabolic syndrome, compared with 6.78% of healthy
      controls (P < .05). CONCLUSION: This study demonstrates that the Maternal Health
      Clinic accurately identifies postpartum patients that have underlying
      cardiovascular risks which make them susceptible to CVD. The clinic may serve as
      an effective primary prevention strategy.

PMID- 24316271
TI  - Reply: To PMID 23791564.

PMID- 24316272
TI  - Cancer and pregnancy: an overview for obstetricians and gynecologists.
AB  - A relatively rare occurrence, pregnancy-associated cancer affects approximately 1
      in 1000 pregnancies. Optimizing treatment of the cancer and minimizing harm to
      the fetus are often dependent on the extent of disease, treatment options
      required, and the impact on the pregnancy as well as the gestational age of
      pregnancy. When malignancy is diagnosed, the obstetrician-gynecologist plays a
      key role in the diagnosis, initial evaluation, and coordination of patient care.
      Furthermore, the obstetrician-gynecologist may be asked to assist in fertility
      planning for young women with a new diagnosis of cancer and may be responsible
      for addressing questions about family-planning needs and the safety of future
      pregnancy. Therefore, the purpose of this article was to provide the obstetrician
      gynecologist with a relevant overview of the current literature regarding
      concurrent pregnancy and cancer diagnoses, management options, including maternal
      and neonatal outcomes, as well as the future needs of young women diagnosed with
      cancer who desire fertility preservation. 

PMID- 24316273
TI  - Term induction of labor and subsequent preterm birth.

PMID- 24316274
TI  - ERK1/2 activation modulates pyocyanin-induced toxicity in A549 respiratory
      epithelial cells.
AB  - Pyocyanin (PCN), a virulence factor produced by Pseudomonas aeruginosa, has many
      damaging effects on mammalian cells. Several lines of evidence suggest that this
      damage is primarily mediated by its ability to generate oxidative stress. However
      mechanisms underlying PCN-induced oxidative injury remain unclear. Although
      oxidative stress and subsequent MAPK signaling has been shown to modulate cell
      death in other models, its role in PCN-induced cytotoxicity remains unknown.
      Therefore the aim of this study was to investigate the role of redox-sensitive
      MAPK in PCN-induced toxicity in A549 cells. Here we show that PCN (50MUM) rapidly
      increased ERK1/2 phosphorylation after 5min. Pre-treatment of A549 cells with the
      MEK1/2 inhibitor U0126 (10MUM) decreased PCN-induced ERK1/2 phosphorylation and
      protected cells against apoptosis and cell injury suggesting a role for ERK
      signalling. In contrast, JNK and p38 MAPK phosphorylation remained unchanged
      following exposure to PCN and pretreatment with either the JNK or p38 MAPK
      inhibitors (10MUM SP600125 and 10MUM SB203580, respectively) did not afford
      protection against PCN toxicity. This would suggest that PCN-induced cytotoxicity
      appears to occur independently of JNK and p38 MAPK signaling pathways. Finally,
      although we confirm that oxidative stress contributes to PCN-induced toxicity,
      our data suggest the contribution of oxidative stress is independent of ERK1/2
      signaling. These findings may provide insight for novel targeted therapies to
      reduce PCN-mediated lung injury in patients with chronic P. aeruginosa
      respiratory infections. 

PMID- 24316275
TI  - Profiling of enantiopure drugs towards aryl hydrocarbon (AhR), glucocorticoid
      (GR) and pregnane X (PXR) receptors in human reporter cell lines.
AB  - In the past decade, a large number of enantiopure drugs were introduced to
      clinical practice, since improved therapeutic effects were demonstrated for one
      of the enantiomers from originally racemic drug. While the therapeutic effects
      and safety of enantiopure drugs were tested prior to their approval, various
      biological enantiospecific activities of these, often "old" drugs, remain to be
      elucidated. In the current paper, we examined enantiospecific effects of
      clinically used enantiopure drugs containing one chiral center in the structure
      (i.e. zopiclone, tamsulosin, tolterodine, modafinil, citalopram) towards aryl
      hydrocarbon (AhR), glucocorticoid (GR) and pregnane X (PXR) receptors in human
      reporter cell lines. The cytotoxicity (IC50), agonist (EC50) and antagonist
      effects (IC50) of R-form, S-form and racemic mixture for each tested drugs were
      determined and compared in AhR-, GR- and PXR-gene reporter cell lines. Since AhR,
      GR and PXR are key regulators of drug metabolism, energy metabolism, immunity and
      play many other physiological functions, the data presented here might be of
      toxicological significance. 

PMID- 24316276
TI  - Inhibition of tumor necrosis factor-alpha and cyclooxigenase-2 by Isatin: a
      molecular mechanism of protection against TNBS-induced colitis in rats.
AB  - Isatin, an indole alkaloid has been shown to have anti-microbial, anti-tumor and
      anti-inflammatory effects. Due to its findings, we evaluated whether this
      alkaloid would have any effect on TNBS-induced colitis. Animals (male Unib:WH
      rats, aged 8 weeks old) were induced colitis through a rectal administration of
      2,4,6-trinitrobenzene sulphonic acid using a catheter inserted 8 cm into the
      rectum of the animals. The rats were divided into two major groups: non-colitic
      and colitic. The colitic group was sub-divided into 6 groups (10 animals per
      group): colitic non-treated, Isatin 3; 6; 12.5; 18.75 and 25 mg/kg. Our main
      results showed that the oral treatment with Isatin 6 and 25 mg/kg were capable of
      avoiding the increase in TNF-alpha, COX-2 and PGE2 levels when compared to the
      colitic non-treated group. Interestingly, the same doses (6 and 25 mg/kg) were
      also capable of preventing the decrease in IL-10 levels comparing with the
      colitic non-treated group. The levels of MPO, (an indirect indicator of
      neutrophil presence), were also maintained lower than those of the colitic non
      treated group. Isatin also prevented the decrease of SOD activity and increase of
      GSH-Px and GSH-Rd activity as well as the depletion of GSH levels. In conclusion,
      both pre-treatments (6 and 25 mg/kg) were capable of protecting the gut mucosa
      against the injury caused by TNBS, through the combination of antioxidant and
      anti-inflammatory properties, which, together, showed a protective activity of
      the indole alkaloid Isatin.

PMID- 24316277
TI  - DNA-based nanostructures: The effect of the base sequence on octamer formation
      from d(XGGYGGT) tetramolecular G-quadruplexes.
AB  - In a previous work we have demonstrated that the DNA sequence CGGTGGT folds into
      a higher order G-quadruplex structure (2Q), obtained by the 5'-5' stacking of two
      unusual G(:C):G(:C):G(:C):G(:C) planar octads belonging to two identical tetra
      stranded parallel quadruplexes, when annealed in the presence of ammonium or
      potassium ions. In the present paper, we discuss the role played by the title
      nucleosides X and Y (where X and Y stand for A, C, G, or T) on the formation and
      stability of 2Q structures formed by the XGGYGGT oligodeoxynucleotides. We found
      that the above mentioned dimerization pathway is not peculiar to the CGGTGGT
      sequence, but is possible for all the remaining CGGYGGT sequences (with Y = A, C,
      or G). Furthermore, we have found that the TGGAGGT sequence, despite the absence
      of the 5'-ending C, is also capable of forming a 2Q-like higher order quadruplex
      by using a slightly different dimerization interface, as characterized by NMR
      spectroscopy. To the best of our knowledge, this is the first characterization of
      a quadruplex multimer formed by an oligodeoxynucleotide presenting a thymine at
      its 5'-end. Examples of such structures were observed previously only in crystals
      and in the presence of non-physiological cations. Our results expand the
      repertoire of DNA quadruplex nanostructures of chosen length and add further
      complexity to the structural polymorphism of G-rich DNA sequences. 

PMID- 24316278
TI  - Defining the impact on yeast ATP synthase of two pathogenic human mitochondrial
      DNA mutations, T9185C and T9191C.
AB  - Mutations in the human mitochondrial ATP6 gene encoding ATP synthase subunit a/6
      (referred to as Atp6p in yeast) are at the base of neurodegenerative disorders
      like Neurogenic Ataxia and Retinitis Pigmentosa (NARP), Leigh syndrome (LS),
      Charcot-Marie-Tooth (CMT), and ataxia telangiectasia. In previous studies, using
      the yeast Saccharomyces cerevisiae as a model we were able to better define how
      several of these mutations impact the ATP synthase. Here we report the
      construction of yeast models of two other ATP6 pathogenic mutations, T9185C and
      T9191C. The first one was reported as conferring a mild, sometimes reversible,
      CMT clinical phenotype; the second one has been described in a patient presenting
      with severe LS. We found that an equivalent of the T9185C mutation partially
      impaired the functioning of yeast ATP synthase, with only a 30% deficit in
      mitochondrial ATP production. An equivalent of the mutation T9191C had much more
      severe effects, with a nearly complete block in yeast Atp6p assembly and an >95%
      drop in the rate of ATP synthesis. These findings provide a molecular basis for
      the relative severities of the diseases induced by T9185C and T9191C. 

PMID- 24316279
TI  - The importance of using realistic evolutionary models for retrodicting proteomes.
AB  - The reconstruction of phylogenetic trees from molecular data requires selecting
      models of molecular evolution that adequately describe known processes of change.
      Operationally, these models optimize molecular changes along branches of the
      trees. The underlying processes must be realistic and must comply with well
      supported biological assumptions. In a recent paper, a new model of proteome
      evolution that penalizes growth of the protein world provides an 'upside down'
      phylogeny and identifies a very complex ancestor of diversified life. Here we
      show that the model is phylogenetically self-inconsistent and at odds with
      considerable background knowledge, including the scale-free property of domain
      networks, genomic scaling laws, and the principle of continuity that supports the
      tenets of ideographic analysis and evolutionary thinking. While technical and
      conceptual limitations invalidate the main conclusions of the study, including
      the existence of bottlenecks in protein evolution caused by planetary cataclysms,
      we use the example to highlight the complexities and pitfalls of retrodiction in
      phylogenetic and phylogenomic analyses and reexamine the framework of ideographic
      exploration that is used in scientific inquiry. 

PMID- 24316280
TI  - Highly divergent mitochondrion-related organelles in anaerobic parasitic
      protozoa.
AB  - The mitochondria have arisen as a consequence of endosymbiosis of an ancestral
      alpha-proteobacterium with a methane-producing archae. The main function of the
      canonical aerobic mitochondria include ATP generation via oxidative
      phosphorylation, heme and phospholipid synthesis, calcium homeostasis, programmed
      cell death, and the formation of iron-sulfur clusters. Under oxygen-restricted
      conditions, the mitochondrion has often undergone remarkable reductive
      alterations of its content and function, leading to the generation of
      mitochondrion-related organelles (MROs), such as mitosomes, hydrogenosomes, and
      mithochondrion-like organelles, which are found in a wide range of
      anaerobic/microaerophilic eukaryotes that include several medically important
      parasitic protists such as Entamoeba histolytica, Giardia intestinalis,
      Trichomonas vaginalis, Cryptosporidium parvum, Blastocystis hominis, and
      Encephalitozoon cuniculi, as well as free-living protists such as Sawyeria
      marylandensis, Neocallimastix patriciarum, and Mastigamoeba balamuthi. The
      transformation from canonical aerobic mitochondria to MROs apparently have
      occurred in independent lineages, and resulted in the diversity of their
      components and functions. Due to medical and veterinary importance of the MRO
      possessing human- and animal-pathogenic protozoa, their genomic, transcriptomic,
      proteomic, and biochemical evidence has been accumulated. Detailed analyses of
      the constituents and functions of the MROs in such anaerobic pathogenic protozoa,
      which reside oxygen-deprived or oxygen-poor environments such as the mammalian
      intestine and the genital organs, should illuminate the current evolutionary
      status of the MROs in these organisms, and give insight to environmental
      constraints that drive the evolution of eukaryotes and their organelles. In this
      review, we summarize and discuss the diverse metabolic functions and protein
      transport systems of the MROs from anaerobic parasitic protozoa. 

PMID- 24316282
TI  - Novel unfolding sequence of banana lectin: Folded, unfolded and natively unfolded
      like monomeric states in guanidine hydrochloride.
AB  - The sequence of unfolding events of dimeric banana lectin (Banlec), as induced by
      guanidine hydrochloride (GdnHCl), has been investigated by size-exclusion HPLC,
      fluorescence, far-UV CD, low temperature phosphorescence and selective chemical
      modification. 8-Anilino-1-naphthalenesulfonate (ANS) binding indicates a
      structured unfolding intermediate which has been characterized as dissociated
      monomer by size-exclusion chromatography. Interestingly, the unfolding elution
      pattern reveals two distinct unfolded states. One is a usual random coil. The
      other represents a novel species having elution behavior and structural
      compactness (Stokes radius) similar to dissociated monomer but showing no regular
      secondary structure as determined by far-UV CD, thus resembling a natively
      unfolded state. N-Bromosuccinimide (NBS) oxidation shows that single tryptophan
      residue remains unmodified in dissociated monomer intermediate while the same is
      oxidized in natively unfolded-like species. Such difference in tryptophan
      environment in these species is supported by acrylamide quenching studies, and
      phosphorescence results at 77 K which show a blue-shift of (0,0) band from 414.8
      nm to 409.2 nm. The present results reveal subtlety of structural characteristics
      of unfolded states of Banlec in GdnHCl, which provide important insight in
      protein unfolding reaction. 

PMID- 24316281
TI  - Pathophysiology of X-linked adrenoleukodystrophy.
AB  - Currently the molecular basis for the clinical heterogeneity of X-linked
      adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all
      different phenotypic variants of X-ALD are mutations in the gene encoding the
      peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly
      adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long
      chain fatty acids from the cytosol into the peroxisome for degradation. The
      phenotypic variability is remarkable ranging from cerebral inflammatory
      demyelination of childhood onset, leading to death within a few years, to adults
      remaining pre-symptomatic through more than five decades. There is no general
      genotype-phenotype correlation in X-ALD. The default manifestation of mutations
      in ABCD1 is adrenomyeloneuropathy, a slowly progressive dying-back axonopathy
      affecting both ascending and descending spinal cord tracts as well as in some
      cases, a peripheral neuropathy. In about 60% of male X-ALD patients, either in
      childhood (35-40%) or in adulthood (20%), an initial, clinically silent, myelin
      destabilization results in conversion to a devastating, rapidly progressive form
      of cerebral inflammatory demyelination. Here, ABCD1 remains a susceptibility
      gene, necessary but not sufficient for inflammatory demyelination to occur.
      Although the accumulation of very long-chain fatty acids appears to be essential
      for the pathomechanism of all phenotypes, the molecular mechanisms underlying
      these phenotypes are fundamentally different. Cell autonomous processes such as
      oxidative stress and energy shortage in axons as well as non-cell autonomous
      processes involving axon-glial interactions seem pertinent to the dying-back
      axonopathy. Various dynamic mechanisms may underlie the initiation of
      inflammation, the altered immune reactivity, the propagation of inflammation, as
      well as the mechanisms leading to the arrest of inflammation after hematopoietic
      stem cell transplantation. An improved understanding of the molecular mechanisms
      involved in these events is required for the development of urgently needed
      therapeutics. 

PMID- 24316283
TI  - Benefits and risks of splenectomy.
AB  - Splenectomy is a powerful therapeutic procedure in a wide variety of medical
      disorders provided that it is not undertaken lightly and the risks are weighed
      against the potential benefits in each individual case. Most of this risk seems
      to be due to the underlying splenectomy indication and not to splenectomy alone.
      There has been an increased tendency in recent years towards splenic preservation
      to prevent not only the risk of subsequent overwhelming post-splenectomy
      infection (OPSI) but the long term risk of cardiovascular complications. As there
      is no condition that can be cured by splenectomy, this paper reviewed the
      rationale behind the indications for, and the associated risks. METHOD:
      Electronic searches of the medline (PubMed) database, Cochrane library, and
      science citation index were performed to identify original published studies on
      splenectomy. Relevant articles were searched from relevant chapters in
      specialized texts and all included.

PMID- 24316284
TI  - Comparison of lovastatin and hyaluronic acid/carboxymethyl cellulose on
      experimental created peritoneal adhesion model in rats.
AB  - OBJECTIVES: The aim of this experimental study was to compare the effectiveness
      and reliability of lovastatin and hyaluronic acid + carboxymethyl cellulose
      (Seprafilm). MATERIALS AND METHODS: Thirty two female Wistar-Albino rats weighing
      between 250 and 300 g were used in the study. The rats were divided into four
      groups as sham, control, lovastatin and Seprafilm each of which contained 8 rats.
      All rats were sacrificed on the 14th day after surgery. Macroscopic adhesion,
      microscopic adhesion and tPA, MDA and NO values were evaluated. RESULTS:
      Macroscopic adhesion formation was significantly lower in the sham and study
      groups than in the control group (p < 0.05). Microscopic classification adhesion
      formation was significantly lower in the sham and study groups than in the
      control group (p < 0.05), and the tPA, MDA and NO values showed statistically
      significant differences among the groups. CONCLUSION: Lovastatin and Seprafilm
      were equally effective in preventing postoperative intra abdominal adhesions. The
      study groups were showed significant superiority to the control group.

PMID- 24316285
TI  - Effect of fibrin sealant on blood loss following total knee arthroplasty: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: A systematic review of randomized controlled trials was conducted to
      examine the efficacy of fibrin sealants for the reduction of postoperative blood
      loss and allogeneic red blood cell transfusion in total knee arthroplasty (TKA).
      METHODS: Studies published through May 2013 were identified from PubMed, Embase,
      the Cochrane library, ScienceDirect, and other databases. Two independent
      reviewers assessed the quality of methodology using the Grade of Recommendations
      Assessment, Development and Evaluation approach and extracted data from
      literature. The mean difference (MD) of blood loss, hemoglobin loss, and risk
      ratios (RR) of transfusion rate and adverse events in the fibrin-treated and
      placebo groups were pooled throughout the study. The relevant data were analyzed
      using Stata 11.0 software. RESULTS: Eight studies were included in the review,
      with a total sample size of 558 patients. The drainage blood loss [MD = -354.02
      mL, 95% confidence interval (CI) (-500.87 to -207.18); P < 0.05], reduction in
      calculated total blood loss [MD = -402.12, 95% CI (-599.16 to -205.08); P <
      0.05], hemoglobin loss [MD = -0.86 g/dL, 95% CI (-1.10 g/dL to -0.61 g/dL); P <
      0.05], and transfusion rate [RR = 0.62, 95% CI (0.45-0.86); P < 0.05] were all
      significantly reduced following treatment with fibrin sealants. There were no
      significant differences in the incidence of adverse events [RR = 0.69, 95% CI
      (0.32-1.59); P > 0.05] among the study groups. CONCLUSIONS: The results of the
      present meta-analysis suggest that fibrin sealants for patients undergoing TKA
      may reduce blood loss and maintain higher hemoglobin levels, particularly when
      fibrin sealants are used at higher dosage. Furthermore, fibrin sealants do not
      increase the risk of postoperative deep vein thrombosis, superficial infection,
      pulmonary embolism, and hematoma. Further evaluation is required to confirm our
      findings before fibrin sealants can be used in patients undergoing TKA. LEVEL OF
      EVIDENCE: II.

PMID- 24316286
TI  - An update and review of simulation in urological training.
AB  - Simulation, if appropriately integrated into surgical training, may provide a
      time efficient, cost effective and safe method of training. The use of simulation
      in urology training is supported by a growing evidence base for its use, leading
      many authors to call for it to be integrated into the curriculum. There is
      growing evidence for the utilisation of part task (technical skills) simulators
      to shorten the learning curve in an environment that does not compromise patient
      safety. There is also evidence that non-technical skills affect patient outcomes
      in the operating room and that high fidelity team based simulation training can
      improve non-technical skills and surgical team performance. This evidence has
      strengthened the argument of surgical educators who feel that simulation should
      be formally incorporated into the urology training curriculum to develop both
      technical and non-technical skills with the aim of optimising performance and
      patient safety. 

PMID- 24316287
TI  - Lung tumors on multimodal radiographs derived from grating-based X-ray imaging--a
      feasibility study.
AB  - PURPOSE: The purpose of this study was to assess whether grating-based X-ray
      imaging may have a role in imaging of pulmonary nodules on radiographs. MATERIALS
      AND METHODS: A mouse lung containing multiple lung tumors was imaged using a
      small-animal scanner with a conventional X-ray source and a grating
      interferometer for phase-contrast imaging. We qualitatively compared the signal
      characteristics of lung nodules on transmission, dark-field and phase-contrast
      images. Furthermore, we quantitatively compared signal characteristics of lung
      tumors and the adjacent lung tissue and calculated the corresponding contrast-to
      noise ratios. RESULTS: Of the 5 tumors visualized on the transmission image, 3/5
      tumors were clearly visualized and 1 tumor was faintly visualized in the dark
      field image as areas of decreased small angle scattering. In the phase-contrast
      images, 3/5 tumors were clearly visualized, while the remaining 2 tumors were
      faintly visualized by the phase-shift occurring at their edges. No additional
      tumors were visualized in either the dark-field or phase-contrast images.
      Compared to the adjacent lung tissue, lung tumors were characterized by a
      significant decrease in transmission signal (median 0.86 vs. 0.91, p = 0.04) and
      increase in dark-field signal (median 0.71 vs. 0.65, p = 0.04). Median contrast
      to-noise ratios for the visualization of lung nodules were 4.4 for transmission
      images and 1.7 for dark-field images (p = 0.04). CONCLUSION: Lung nodules can be
      visualized on all three radiograph modalities derived from grating-based X-ray
      imaging. However, our initial data suggest that grating-based multimodal X-ray
      imaging does not increase the sensitivity of chest radiographs for the detection
      of lung nodules.

PMID- 24316288
TI  - Deleterious effects of osteoarthritis on the structure and function of the
      meniscal enthesis.
AB  - OBJECTIVE: The ability of menisci to prevent osteoarthritis (OA) is dependent on
      the integrity of the complex meniscal entheses, the attachments of the menisci to
      the underlying subchondral bone (SB). The goal of this study was to determine
      mechanical and structural changes in meniscal entheses after the onset of OA.
      DESIGN: Healthy and osteoarthritic meniscal entheses were evaluated for changes
      in histomorphological characteristics, mineralization, and mechanical properties.
      Glycosaminoglycans (GAG) and calcium in the insertion were evaluated with
      histological staining techniques. The extent of calcium deposition was assessed
      and tidemark (TM) integrity was quantified. Changes in the mineralized zone of
      the insertion were examined using micro-computed tomography (MUCT) to determine
      bone mineral density, cortical zone thickness, and mineralization gradient.
      Mechanical properties of the entheses were measured using nano-indentation
      techniques to obtain material properties based on viscoelastic analysis. RESULTS:
      GAG thickness in the calcified fibrocartilage (CFC) zone and calcium content were
      significantly greater in osteoarthritic anterior meniscal entheses. TM integrity
      was significantly decreased in OA tissue, particularly in the medial anterior
      (MA) enthesis. The mineralized zone of osteoarthritic meniscal entheses was
      significantly thicker than in healthy entheses and showed decreased bone mineral
      density. Fitting of mineralization data to a sigmoidal Gompertz function revealed
      a lower rate of increase in mineralization in osteoarthritic tissue. Analysis of
      viscoelastic mechanical properties revealed increased compliance in
      osteoarthritic tissue. CONCLUSIONS: These data suggest that significant changes
      occur at meniscal enthesis sites with the onset of OA. Mechanical and structural
      changes in meniscal entheses may contribute to meniscal extrusion, which has been
      shown to increase the progression of OA.

PMID- 24316290
TI  - A rare G1P[6] super-short human rotavirus strain carrying an H2 genotype on the
      genetic background of a porcine rotavirus.
AB  - Rotavirus strains with a rearranged 11th genome segment may show super-short RNA
      electropherotypes. Examples from human strains were limited to seven strains,
      69M, 57M, B37, Mc345, AU19, B4106 and BE2001, which have a variety of G and P
      genotypes. AU19 is a rare G1P[6] human rotavirus strain detected in a Japanese
      infant with severe acute gastroenteritis. This study was undertaken to better
      understand the origin of AU19 by determining the genotype constellation of AU19.
      Upon nearly-full genome sequencing, AU19 had a G1-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H2
      genotype constellation. Possession of I5 and A8 genotypes is indicative of its
      porcine rotavirus origin, whereas possession of H2 genotype is indicative of its
      DS-1 like human rotavirus origin. At the phylogenetic lineage level for the
      genome segments that share the genotype between porcine and human rotaviruses,
      the VP1-4, VP7, NSP3-4 genes were most closely related to those of porcine
      rotaviruses, but the origin of the NSP2 gene was inconclusive. As to the NSP5
      gene, the lineage containing AU19 and the other three super-short human strains,
      69M, 57M and B37, carrying the H2 genotype (H2b) clustered with the lineage to
      which DS-1- like short strains belonged (H2a) albeit with an insignificant
      bootstrap support. Taken all these observations together, AU19 was likely to
      emerge as a consequence of interspecies transmission of a porcine rotavirus to a
      child coupled with the acquisition of a rare H2b genotype by genetic reassortment
      probably from a co-circulating human strain. The addition of the AU19 NSP5
      sequence to much homogeneous H2b genotypes shared by previous super-short
      rotavirus strains made the genetic diversity of H2b genotypes as diverse as that
      of the H2a genotype, lending support to the hypothesis that super-short strains
      carrying H2b genotype have long been circulating unnoticed in the human
      population. 

PMID- 24316291
TI  - Medical entomology--back to the future?
AB  - Some of problems and challenges facing Medical/Veterinary Entomology are
      presented from my perspective, focusing on the current millennium. Topics include
      anthropogenic environmental changes created by population growth, administrative
      problems hindering science's response to these changes, and some of the
      scientific discoveries potentially providing solutions. As the title implies,
      many recent research discoveries have yet to be translated into major changes in
      control approaches for the major vectorborne public health problems, thereby
      providing an interesting mix of modern surveillance technology used to track
      problems and direct historical intervention solutions. 

PMID- 24316289
TI  - Reducing dietary loading decreases mouse temporomandibular joint degradation
      induced by anterior crossbite prosthesis.
AB  - OBJECTIVE: Dietary loading has been reported to have an effect on
      temporomandibular joint (TMJ) remodeling via periodontal-muscular reflex. We
      therefore examined whether reducing dietary loading decreased TMJ degradation
      induced by the unilateral anterior crossbite prosthesis as we recently reported.
      METHODS: Forty 6-week-old female C57BL/6J mice were randomly divided into two
      experimental and two control groups. One experimental and one control group
      received small-size diet and the other two groups received large-size diet.
      Unilateral anterior crossbite prosthesis was created in the two experimental
      groups. The TMJ samples were collected 3 weeks after experimental operation.
      Histological changes in condylar cartilage and subchondral bone were assessed by
      Hematoxylin & Eosin, toluidine blue, Safranin O and tartrate-resistant acid
      phosphatase staining. Real-time polymerase chain reaction (PCR) and/or
      immunohistochemistry were performed to evaluate the expression levels of Collagen
      II, Aggrecan, a disintegrin and metalloproteinase with thrombospondin motifs 5
      (ADAMTS-5) and RANKL/RANK/OPG in TMJ condylar cartilage and/or subchondral bone.
      RESULTS: Thinner and degraded cartilage, reduced cartilage cellular density,
      decreased expression levels of Collagen II and Aggrecan, loss of subchondral bone
      and enhanced osteoclast activity were observed in TMJs of both experimental
      groups. However, the cartilage degradation phenotype was less severe and
      cartilage ADAMTS-5 mRNA was lower while OPG/RANKL ratio in cartilage and
      subchondral bone was higher in the small-size than large-size diet experimental
      group. No differences of histomorphology and the tested molecules were found
      between the two control groups. CONCLUSIONS: The current findings suggest that a
      lower level of functional loading by providing small-size diet could reduce TMJ
      degradation induced by the biomechanical stimulation from abnormal occlusion.

PMID- 24316292
TI  - Multiple lines of evidence on the genetic relatedness of the parthenogenetic and
      bisexual Haemaphysalis longicornis (Acari: Ixodidae).
AB  - As an obligate hematophagous ectoparasite, the hard tick Haemaphysalis
      longicornis exhibits two reproductive strategies, bisexual reproduction, and
      obligate parthenogenesis, which have attracted a widespread attention. However,
      the speciation of parthenogenetic population remained ambiguous due to its
      similarity in morphology but the remarkable differences in cytogenetics as
      compared with those of the bisexual ones. In the present study, we explored
      several new lines of genetic evidence to resolve this controversial issue. The
      number of the chromosomes in two lineages was checked by classical methods and
      their total DNA levels were determined utilizing flowcytometry. In addition, the
      sequences of 12S rDNA, 16S rDNA, cytochrome c oxidase I and II (COI, COII) and
      internal transcribed spacer-2 (ITS-2) genes were used to assess their
      phylogenetic relationship. We observed that the chromosome ploidy of bisexual and
      parthenogenetic H. longicornis collected by our laboratory was diploid and
      triploid, respectively. Flowcytometry analysis indicated a ratio close to 2:3 in
      the DNA contents of bisexual to parthenogenetic H. longicornis. Although the
      chromosome ploidy is different, their gene sequences are extremely similar.
      Analogous to the intra-species genetic difference of other invertebrates,
      sequence differences of all loci examined are below 2%. Phylogenetic trees
      constructed from 12S rDNA, 16S rDNA, COI, and ITS-2 genes revealed that they were
      all in the same monophyletic clade instead of splitting independently into
      evolutional branches. Moreover, according to 4* Rule, the K/theta ratio of two
      reproductive populations calculated based on COI was much smaller than four,
      strongly supporting that they belong to the same species. Therefore, we conclude
      that the evolutionary process just disturbs the chromosome ploidy and the sexual
      determination of parthenogenetic population and that it would be better to
      consider parthenogenetic H. longicornis as a metapopulation rather than a cryptic
      species. 

PMID- 24316293
TI  - Relevance of bone anomalies in patients with thoracic outlet syndrome.
AB  - BACKGROUND: Skeletal anomalies are recognized as potential causes of thoracic
      outlet syndrome (TOS); however, there is a paucity of information regarding the
      specific bone anomalies associated with TOS and their relative incidence among
      the different clinical types of TOS. This study describes the prevalence of bone
      anomalies in a population with TOS. METHODS: A retrospective chart review of the
      clinical records and imaging studies of all patients who were surgically treated
      at our institution for TOS between 1991-2011 was conducted. A descriptive
      analysis of the cohort of patients with associated bone anomalies was performed
      and compared with the cohort of patients without bone anomalies. RESULTS: During
      the study period, 400 patients underwent operative procedures for TOS. Of these,
      115 (29%) harbored a bone anomaly and the remaining 285 did not. The bone
      anomalies included 80 (69%) cervical ribs, 25 (22%) clavicular anomalies, and 10
      (9%) isolated first rib aberrations. Ninety (78%) of the bone anomalies were
      congenital, while 25 (22%) were posttraumatic. The bone anomaly cohort was
      predominantly female (76%), with an average age of 36 years. The distribution of
      neurogenic, arterial, and venous types of TOS in the cohort with bone anomalies
      was 63%, 33%, and 4%, respectively, while it was 51% neurogenic, 11% arterial,
      and 38% venous in the cohort without bone anomalies. These distributions were
      significantly different (chi-squared: 56.75; P < 0.0001). The likelihood of
      neurogenic compression was roughly equivalent between the 2 cohorts (odds ratio
      [OR]: 1.6; P = 0.03), while the likelihood of arterial compression was much
      higher in the presence of a bone anomaly (OR: 4.0; P < 0.001) and the likelihood
      of venous compression was much lower in the presence of bone anomaly (OR: 0.07; P
      < 0.001). Conversely, 33% of all neurogenic TOS cases, 54% of all arterial TOS
      cases, and 4% of all venous TOS cases were associated with a bone anomaly.
      CONCLUSIONS: In our experience, the incidence of bone anomalies among patients
      treated for TOS was 29%, which is higher than previously reported. Cervical ribs
      were present in 20% of our patients with TOS, an estimated 40 times higher
      prevalence than that in the general population. However, acquired clavicular
      deformities and isolated abnormal first ribs were found in 9% of our patients,
      accounting for almost one-third of all bone anomalies present in this TOS
      population. The incidence of bone anomalies is rather different among the
      subtypes of TOS. The strongest association with the presence of a bone anomaly
      occurs in patients with arterial TOS, although 46% of all our arterial TOS cases
      did not have a bone anomaly. The presence of bone anomalies does not seem to
      influence the occurrence of neurogenic TOS, while venous TOS likely has no
      association with congenital bone anomalies, but occasionally mid and medial
      clavicular fracture calluses may cause venous TOS.

PMID- 24316294
TI  - Characterization of a novel primary culture system of adult zebrafish brainstem
      cells.
AB  - Adult zebrafish (Danio rerio) have a remarkable ability to restore function after
      an injury to the brain or spinal cord. The molecular and cellular mechanisms
      underlying this phenomenon are not fully understood. To enable investigation of
      these mechanisms we have developed an in vitro model system from the adult
      zebrafish brainstem, which can be maintained under serum-containing and serum
      free conditions. While cultures are predominantly neuronal, they also contain
      glia and stem progenitor cells. Various stages of cellular differentiation are
      observed among both neuronal and non-neuronal populations. Quantitative
      morphological results revealed typical cellular growth over a two-week period. We
      argue that our novel brainstem culture model offers a powerful tool for the
      studies of axonal growth, neurogenesis, and regeneration in the adult zebrafish
      central nervous system. 

PMID- 24316295
TI  - Second order blind identification on the cerebral cortex.
AB  - Blind source separation (BSS) methods have become standard brain imaging tools
      and are routinely used for noise and artifact removal, as well as for extracting
      related spatial and temporal components from brain signals. Despite their
      popularity, BSS methods have rarely been used to explore maps of cortical
      thickness and sulcal folding patterns. Our limited knowledge of the relationship
      between cortical morphometry, brain development and pathologies of the central
      nervous system makes BSS methods ideal investigative tools. We propose a novel
      spatial BSS method tailored for application to the cerebral cortex based on the
      second order blind identification (SOBI) method. Our method outperforms the
      regular SOBI and popular FastICA BSS methods on simulations. Application to maps
      of cortical thickness and curvature from normal controls reveals original
      structural networks. 

PMID- 24316296
TI  - The will to persevere induced by electrical stimulation of the human cingulate
      gyrus.
AB  - Anterior cingulate cortex (ACC) is known to be involved in functions such as
      emotion, pain, and cognitive control. While studies in humans and nonhuman
      mammals have advanced our understanding of ACC function, the subjective
      correlates of ACC activity have remained largely unexplored. In the current
      study, we show that electrical charge delivery in the anterior midcingulate
      cortex (aMCC) elicits autonomic changes and the expectation of an imminent
      challenge coupled with a determined attitude to overcome it. Seed-based, resting
      state connectivity analysis revealed that the site of stimulation in both
      patients was at the core of a large-scale distributed network linking aMCC to the
      frontoinsular and frontopolar as well as some subcortical regions. This report
      provides compelling, first-person accounts of electrical stimulation of this
      brain network and suggests its possible involvement in psychopathological
      conditions that are characterized by a reduced capacity to endure psychological
      or physical distress. 

PMID- 24316297
TI  - [Reliability of retinal imaging screening in retinopathy of prematurity].
AB  - INTRODUCTION: The retinopathy of prematurity (ROP) is a potentially avoidable
      cause of blindness in children. The advances in neonatal care make the survival
      of extremely premature infants, who show a greater incidence of the disease,
      possible. The aim of the study is to evaluate the reliability of ROP screening
      using retinography imaging with the RetCam 3 wide-angle camera and also study the
      variability of ROP diagnosis depending on the evaluator. MATERIAL AND METHODS:
      The indirect ophthalmoscopy exam was performed by a Pediatric ROP-Expert
      Ophthalmologist. The same ophthalmologist and a technician specialized in digital
      image capture took retinal images using the RetCam 3 wide-angle camera. A total
      of 30 image sets were analyzed by 3 masked groups: group A (8 ophthalmologists),
      group B (5 experts in vision), and group C (2 ROP-expert ophthalmologists).
      RESULTS: According to the diagnosis using indirect ophthalmoscopy, the
      sensitivity (26-93), Kappa (0.24-0.80), and the percent agreement were
      statistically significant in group C for the diagnosis of ROP Type 1. In the
      diagnosis of ROP Type 1+Type 2, Kappa (0.17-0.33) and the percent agreement (58
      90) were statistically significant, with higher values in group C. CONCLUSION:
      The diagnosis, carried out by ROP-expert ophthalmologists, using the wide-angle
      camera RetCam 3 has proved to be a reliable method.

PMID- 24316298
TI  - [Accessory scrotum].

PMID- 24316299
TI  - [Cardiac tamponade: role of echocardiography in a Pediatric Intensive Care Unit].

PMID- 24316300
TI  - [Vasa praevia rupture in velamentous insertion of the umbilical cord: the
      importance of prenatal diagnosis].
AB  - Vasa praevia is a rare condition in which the foetal blood vessels cross the
      foetal membranes of the lower segment of the uterus below the presenting part. It
      has a high foetal mortality due to foetal exsanguination resulting from foetal
      vessels tearing when the membranes rupture. Prenatal diagnosis can reduce or even
      prevent foetal mortality, but it requires a high level of suspicion. For this
      reason, pregnant women with risk factors of vasa praevia should be examined using
      transvaginal ultrasound in combination with colour Doppler, and if the diagnosis
      is made, elective delivery by caesarean and aggressive resuscitation of the new
      born is indicated. 

PMID- 24316301
TI  - An in vitro study on catecholamine modulation of ovarian steroidogenic activity
      in the catfish Heteropneustes fossilis.
AB  - In the present study, alpha-methylparatyrosine (alpha-MPT), a tyrosine
      hydroxylase inhibitor was used to impair ovarian catecholaminergic activity in
      vitro. The consequent effects on catecholamine (CA) levels were correlated with
      follicular steroid production. l-dihdroxyphenylalanine (l-DOPA, the precursor of
      CA) and human gonadotropin (hCG) were supplemented to reverse the effect of alpha
      MPT. The experiments were conducted in two reproductive phases, namely
      preparatory and pre-spawning phases in female catfish Heteropneustes fossilis.
      The incubation with alpha-MPT inhibited ovarian l-DOPA, dopamine (DA),
      norepinephrine (NE) and epinephrine (EP) levels and the l-DOPA supplementation
      compensated the inhibitory effect. The level of tyramine (TR) was increased by
      the alpha-MPT treatment but inhibited by the l-DOPA supplementation. alpha-MPT
      produced stage-specific (seasonal) effects on ovarian estradiol-17beta (E2); in
      the preparatory phase, E2 was decreased significantly at both 12 and 24h and in
      the pre-spawning phase, the level was stimulated over the respective control
      groups. The changes were higher at 24h in both phases. l-DOPA and hCG increased
      the E2 level significantly in the preparatory phase and reversed the inhibitory
      effect of alpha-MPT in the co-incubation groups. In the pre-spawning phase, alpha
      MPT-stimulated the E2 level compared to the control groups, which was reversed by
      l-DOPA, hCG, or by both, in co-incubations. In contrast, the alpha-MPT treatment
      decreased progesterone (P4), 17-hydroxyprogesterone and 17,20beta-dihydroxy-4
      prenen-3-one (17,20beta-DP) in a duration-dependent manner while the co
      incubations with l-DOPA, hCG, or by both, significantly reversed the inhibitory
      effect. These results suggest that ovarian CAs (DA, NE and EP) may exert
      differential and stage-specific effects on E2, inhibition in the preparative
      phase and stimulation in the pre-spawning phase. The progestin steroids appear to
      be stimulated by CAs. In conclusion, this study highlights a possible
      direct/causal functional interaction between CA activity and gonadotropin on
      steroidogenic activity, and that CAs may be involved in regulating temporal
      secretion of the hormones through causing the shift in steroidogenic pattern. 

PMID- 24316302
TI  - Evidence for intercellular communication in mosquito renal tubules: a putative
      role of gap junctions in coordinating and regulating the rapid diuretic effects
      of neuropeptides.
AB  - Adult female mosquitoes require a blood meal from a vertebrate host to
      successfully reproduce. During a single blood feeding, a female may ingest more
      than the equivalent of her own body mass, resulting in an acute stress to osmotic
      and ionic homeostasis. In response to this stress, the renal (Malpighian) tubules
      mediate a rapid diuresis that commences as soon as blood is ingested. The
      diuresis is regulated by neuropeptides (e.g., kinins, calcitonin-like peptide)
      that act on receptors in the Malpighian tubule epithelium. Interestingly, the
      expression of these receptors is discontinuous throughout the epithelium, which
      raises the question as to how Malpighian tubules mount such a rapid and
      synchronized response to neuropeptide stimulation. Here we propose a hypothesis
      that gap junctions functionally couple the epithelial cells of Malpighian
      tubules, resulting in a coordinated physiological response to the binding of
      neuropeptides. We review recent, relevant literature on the electrophysiology,
      physiology, and molecular biology of mosquito Malpighian tubules that indicate
      the presence of gap junctions in the epithelium. We also provide new
      physiological and immunochemical data that are consistent with the proposed
      hypothesis. 

PMID- 24316304
TI  - Towards understanding promiscuity in multidrug efflux pumps.
AB  - Drug export from cells is a major factor in the acquisition of cellular
      resistance to antimicrobial and cancer chemotherapy, and poses a significant
      threat to future clinical management of disease. Many of the proteins that
      catalyse drug efflux do so with remarkably low substrate specificity, a
      phenomenon known as multidrug transport. For these reasons we need a greater
      understanding of drug recognition and transport in multidrug pumps to inform
      research that attempts to circumvent their action. Structural and computational
      studies have been heralded as being great strides towards a full elucidation of
      multidrug recognition and transport. In this review we summarise these advances
      and ask how close we are to a molecular understanding of this remarkable
      phenomenon. 

PMID- 24316303
TI  - Marching to the beat of the ring: polypeptide translocation by AAA+ proteases.
AB  - ATP-dependent proteases exist in all cells and are crucial regulators of the
      proteome. These machines consist of a hexameric, ring-shaped motor responsible
      for engaging, unfolding, and translocating protein substrates into an associated
      peptidase for degradation. Here, we discuss recent work that has established how
      the six motor subunits coordinate their ATP-hydrolysis and translocation
      activities. The closed topology of the ring and the rigidity of subunit/subunit
      interfaces cause conformational changes within a single subunit to drive motions
      in other subunits of the hexamer. This structural effect generates allostery
      between the ATP-binding sites, leading to a preferred order of binding and
      hydrolysis events among the motor subunits as well as a unique biphasic mechanism
      of translocation. 

PMID- 24316305
TI  - Incorporation of anti-angiogenesis therapy in the management of advanced ovarian
      carcinoma--mechanistics, review of phase III randomized clinical trials, and
      regulatory implications.
AB  - Despite survival gains achieved nearly two decades ago with combination platinum-
      and taxane-based intravenous chemotherapy, overall survival curves have remained
      relatively unchanged during the 21st century using newer cytotoxic agents.
      Although combined intravenous-intraperitoneal (IV-IP) chemotherapy is promising,
      tolerability remains a significant issue. An emphasis has been placed on
      exploring dose dense schedules and targeted agents. Vascular endothelial growth
      factor (VEGF) has emerged as an important therapeutic target in several solid
      tumors including ovarian carcinoma. The monoclonal antibody, bevacizumab, binds
      VEGF, thus preventing activation of the VEGF receptor (VEGFR) leading to
      inhibition of tumor angiogenesis. To date eight phase 3 randomized controlled
      trials incorporating anti-angiogenesis therapy in the treatment of newly
      diagnosed and recurrent ovarian carcinoma have met their primary endpoints. Four
      of these trials included bevacizumab and were reported from 2010 to 2012. During
      2013, the other four studies were reported, each studying one of the following
      novel anti-angiogenesis agents: pazopanib, cediranib, trebananib, and nintedanib.
      Importantly, none of these drugs have been approved by the United States Food and
      Drug Administration (US FDA) for the treatment of ovarian cancer. The purpose of
      this review will be to highlight both VEGF-dependent and non-VEGF dependent
      angiogenic pathways in ovarian cancer and discuss the phase 3 experiences and
      regulatory implications of targeting the tumor microenviroment with anti
      angiogenesis therapy. 

PMID- 24316306
TI  - Ovarian cancer screening--current status, future directions.
AB  - Evidence of a mortality benefit continues to elude ovarian cancer (OC) screening.
      Data from the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening
      Trial which used a screening strategy incorporating CA125 cut-off and
      transvaginal ultrasound has not shown mortality benefit. The United Kingdom
      Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is using the Risk of
      Ovarian Cancer (ROC) time series algorithm to interpret CA125, which has shown an
      encouraging sensitivity and specificity however the mortality data will only be
      available in 2015. The article explores the impact of growing insights into
      disease aetiology and evolution and biomarker discovery on future screening
      strategies. A better understanding of the target lesion, improved design of
      biomarker discovery studies, a focus on detecting low volume disease using cancer
      specific markers, novel biospecimens such as cervical cytology and targeted
      imaging and use of time series algorithms for interpreting markers profile
      suggests that a new era in screening is underway. 

PMID- 24316307
TI  - Pathologic features associated with resolution of complex atypical hyperplasia
      and grade 1 endometrial adenocarcinoma after progestin therapy.
AB  - OBJECTIVE: To determine the response of complex atypical hyperplasia (CAH) and
      well differentiated endometrioid adenocarcinoma of the uterus (WDC) to progestin
      therapy and whether pre-treatment estrogen and progesterone receptor status
      predicts outcome. METHODS: We performed a retrospective review encompassing women
      treated with progestin therapy for CAH or WDC at two institutions.
      Clinicopathologic, treatment, and recurrence data were recorded. Pre/post
      treatment pathologic evaluation was performed. SAS 9.2 was used for statistical
      analyses. RESULTS: Forty-six patients were included. The median age was 35, and
      median BMI was 36.9. Thirty-seven percent were diagnosed with CAH and 63% had
      WDC. Megestrol acetate was the most commonly used agent (89%); 24% received
      multiple progestin therapies. Median treatment length was 6 months (range, 1-84);
      36% of the patients underwent eventual hysterectomy, and 17.4% had carcinoma in
      their uterine specimens (8 primary endometrial, 1 primary ovarian). After a
      median follow-up of 35 months (range, 2-162), 65% experienced a complete response
      (CR), 28% had persistent or progressive disease, and 23% had a CR followed by
      recurrence. On univariate analysis, decreased post-treatment glandular
      cellularity (p = 0.0006), absence of post-treatment mitotic figures (p = 0.0008),
      and use of multiple progestin agents (p = 0.025) were associated with CR;
      however, only decreased glandular cellularity was significant on multivariate
      analysis (p = 0.007). Estrogen and progesterone receptor expression was not
      associated with treatment response. CONCLUSION: In women with CAH or WDC, the
      overall response rate to progestin therapy was 65%; pre-treatment
      estrogen/progesterone receptor status did not predict response to treatment.

PMID- 24316308
TI  - Dual mTORC1/2 inhibition in a preclinical xenograft tumor model of endometrial
      cancer.
AB  - OBJECTIVES: Up to 70% of endometrioid endometrial cancers carry PTEN gene
      deletions that can upregulate mTOR activity. Investigational mTOR kinase
      inhibitors may provide a novel therapeutic approach for these tumors. Using a
      xenograft tumor model of endometrial cancer, we assessed the activity of mTOR and
      downstream effector proteins in the mTOR translational control pathway after
      treatment with a dual mTOR complex 1 and 2 (mTORC1/2) catalytic inhibitor (PP242)
      compared to that of an allosteric mTOR complex 1 (mTORC1) inhibitor (everolimus,
      RAD001). METHODS: Grade 3 endometrioid endometrial cancer cells (AN3CA) were
      xenografted into nude mice. Animals were treated with PP242, PP242 and
      carboplatin, carboplatin, RAD001, and RAD001 and carboplatin. Mean tumor volume
      was compared across groups by ANOVA. Immunoblot analysis was performed to assess
      mTORC1/2 activity using P-Akt, P-S6 and P-4E-BP1. RESULTS: The mean tumor volume
      of PP242+carboplatin was significantly lower than in all other treatment groups,
      P < 0.001 (89% smaller). The RAD001+carboplatin group was also smaller, but this
      did not reach statistical significance (P = 0.097). Immunoblot analysis of tumor
      lysates treated with PP242 demonstrated inhibition of activated P-Akt.
      CONCLUSIONS: Catalytic mTORC1/2 inhibition demonstrates clear efficacy in tumor
      growth control that is enhanced by the addition of a DNA damage agent,
      carboplatin. Targeting mTORC1/2 leads to inhibition of Akt activation and strong
      downregulation of effectors of mTORC1, resulting in downregulation of protein
      synthesis. Based on this study, mTORC1/2 kinase inhibitors warrant further
      investigation as a potential treatment for endometrial cancer.

PMID- 24316309
TI  - Clinical implications of aldo-keto reductase family 1 member C3 and its
      relationship with lipocalin 2 in cancer of the uterine cervix.
AB  - OBJECTIVE: Over-expression of the aldo-keto reductase family 1 member C3 (AKR1C3)
      has been demonstrated in many human cancers. Lipocalin 2 (LCN2) is reported to
      inhibit cervical cancer metastasis but little is known regarding its relationship
      with AKR1C3 in the development and progression of uterine cervical cancer. This
      study aimed to investigate the involvement of AKR1C3 and its relationship with
      LCN2 in cervical cancer. METHODS: The roles of AKR1C3 and LCN2 were investigated
      using the lentivirus shRNA system in SiHa and Caski cervical cancer cells. LCN2
      and matrix metalloproteinase-2 (MMP-2) promoters were constructed to demonstrate
      transcriptional regulation by shAKR1C3 and shLCN2, respectively. The influences
      of metastatic phenotypes were analyzed by wound healing, Boyden chamber, and
      immunofluorescence assays. The activity of MMP-2 was determined by zymography
      assay. The impacts of AKR1C3 and LCN2 on patient prognosis were evaluated using
      tissue microarrays by Cox regression and Kaplan-Meier models. RESULTS: Silencing
      of the AKR1C3 gene increased the expression of LCN2 and decreased the migratory
      and invasive abilities and changed the cytoskeleton of cervical cancer cells.
      When AKR1C3 was over-expressed, it decreased LCN2 promoter activity and LCN2
      expression and increased cell migration. The mRNA level and enzyme activity of
      MMP-2 increased in silenced LCN2 cells. Positive AKR1C3 and negative LCN2 were
      correlated with higher recurrence and poorer survival of cervical cancer
      patients. CONCLUSIONS: Silencing of AKR1C3 increases LCN2 expression and inhibits
      metastasis in cervical cancer. Both AKR1C3 and LCN2 serve as molecular targets
      for cancer therapy to improve the clinical outcome of cervical cancer patients.

PMID- 24316310
TI  - Endometrial cancer in Asian and American Indian/Alaskan Native women: tumor
      characteristics, treatment and outcome compared to non-Hispanic white women.
AB  - OBJECTIVE: The objective of this study is to compare survival of Asian (AS),
      American Indian/Alaskan Native (AI/AN) and non-Hispanic white (NHW) women with
      endometrial adenocarcinoma (EC). METHODS: Patients with EC were identified from
      the Surveillance, Epidemiology, and End Results program from 1988 to 2009. Kaplan
      Meier survival methods and Cox proportional hazards regression were performed.
      RESULTS: Of the 105,083 women, 97,763 (93%) were NHW, 6699 (6.4%) were AS and 621
      (0.6%) were AI/AN. AS and AI/AN were younger than NHW with mean age of 57.7 and
      56.5 vs. 64.3 years (p < 0.001 and 0.059). Advanced stage and high-risk histology
      were more prominent in AS than NHW (15.6% vs. 13.3%, p = 0.04, 10.6% vs. 9.6%, p=
      0.041). Lymphadenectomy was performed more frequently in AS than NHW (56.7% vs.
      48.2%, p < 0.001). Asian immigrants were younger than Asian natives (mean age 57
      vs. 60.5 years, p < 0.001). In multivariate analysis, AS had better overall (OS)
      (HR 0.86, 95% CI 0.81-0.91, p < 0.001) and cancer-specific survival (CSS) (HR
      0.92, 95% CI 0.84-1.00, p = 0.05) than NHW. Further, Asian immigrants had better
      OS (HR 0.83, 95% CI 0.73-0.94, p = 0.002) and CSS (HR 0.66, 95% CI 0.54-0.80, p <
      0.001) than Asian natives. In contrast, AI/AN had worse OS (HR 1.35, 95% CI 1.15
      1.59, p < 0.001) but no difference in CSS (HR 1.06, 95% CI 0.80-1.40, p = 0.69)
      than NHW. CONCLUSIONS: Asians were younger at presentation, more likely to have
      lymphadenectomy and had an improved outcome compared to NHW. Interestingly, Asian
      immigrants had more favorable outcome than Asians born in the US. Further studies
      are warranted to find possible explanations for such a difference.

PMID- 24316311
TI  - The alteration of lipid bilayer dynamics by phloretin and 6-ketocholestanol.
AB  - Lipid bilayer properties are quantified with a variety of arbitrary selected
      parameters such as molecular packing and dynamics, electrostatic potentials or
      permeability. In the paper we determined the effect of phloretin and 6
      ketocholestanol (dipole potential modifying agents) on the membrane hydration and
      efficiency of the trans-membrane water flow. The dynamics of water molecules
      within the lipid bilayer interface was evaluated using solvent relaxation method,
      whereas the osmotically induced trans-membrane water flux was estimated with the
      stopped-flow method using the liposome shrinkage kinetics. The presence of
      phloretin or 6-ketocholestanol resulted in a change of both, the interfacial
      hydration level and osmotically driven water fluxes. Specifically, the presence
      of 6-ketocholestanol reduced the amount and mobility of water in the membrane
      interface. It also slows the osmotically induced water flow. The interfacial
      hydration change caused by phloretin was much smaller and the effect on
      osmotically induced water flow was opposite to that of 6-ketocholestanol. 

PMID- 24316312
TI  - Comment on "Advanced glycation endproducts in food and their effects on health"
      by Poulsen et al. (2013) Food and Chemical Toxicology 60, 10-37.

PMID- 24316313
TI  - A note on Toxicodendron vernicifluum (Stokes) F.A. Barkley.

PMID- 24316314
TI  - Relationship between fermented papaya preparation supplementation, erythrocyte
      integrity and antioxidant status in pre-diabetics.
AB  - Erythrocytes and their membranes are favorable models to study the relationship
      between diabetes and susceptibility of erythrocytes to oxidative stress damage.
      The recommendation for the use of fermented papaya preparation (FPP) as a
      functional food for dietary management of type 2 diabetes was evaluated by
      assessing its effect on the human antioxidant status and erythrocyte integrity on
      a multi-ethnical pre-diabetic population. The in vivo effect of FPP was compared
      with its in vitro free radical scavenging potentials. FPP exhibited potent in
      vitro free radical scavenging activities thought to be attributed to residual
      phenolic or flavonoid compounds. Low doses of FPP significantly reduced the
      susceptibility of human erythrocytes to undergo free radical-induced hemolysis.
      The intake of 6g FPP/day for a period of 14weeks was observed to significantly
      reduce the rate of hemolysis and accumulation of protein carbonyls in the blood
      plasma of pre-diabetics. That FPP consumption on a daily basis can strengthen the
      antioxidant defense system in vivo was clearly demonstrated by the marked
      increase of total antioxidant status in the FPP-supplemented pre-diabetics. That
      FPP maintains the integrity of erythrocytes could benefit the strategies to
      improve the quality of future blood products. 

PMID- 24316315
TI  - Comment on "Toxic hepatitis in a group of 20 male body-builders taking dietary
      supplements" by Timcheh-Hariri et al. (2012), Food and Chemical Toxicology 50,
      3826-3832: alleged adverse effects of creatine supplementation and the lack of
      appreciation of the wide gap between experimental and clinical studies.

PMID- 24316316
TI  - Attenuating effects of omega-3 fatty acids (Omegaven) on irradiation-induced
      intestinal injury in mice.
AB  - Gastrointestinal injury is a major cause of death following exposure to high
      levels of irradiation, and no effective treatments are currently available. In
      this study, we examined the effect of omega-3 fatty acids (Omegaven) on
      intestinal injury of BALB/c mice induced by irradiation. Intravenously
      administered 3 days prior to irradiation for 7 consecutive days, Omegaven was
      shown to improve survival, intestinal morphology including villous height, crypt
      height and mucosal thickness and the intestinal proliferation compared with
      saline control. Omegaven also normalized the levels of circulating tumor necrosis
      factor alpha (TNF-alpha) and interleukin-6 (IL-6), attenuated the increase of
      diamino oxidase (DAO) activity and malondialdehyde (MDA) level and recovered the
      decrease of superoxide dismutase (SOD) activity. Meanwhile, Omegaven attenuated
      the myelosuppression caused by irradiation. In conclusion, our results suggest
      that Omegaven enhanced the survival of irradiated mice and minimized the effects
      of radiation on gastrointestinal injury.

PMID- 24316317
TI  - The influence of fatty acids on determination of human serum albumin thiol group.
AB  - During investigation of the changes of the Cys34 thiol group of human serum
      albumin (HSA) (isolated by affinity chromatography with Cibacron Blue (CB)) in
      diabetes, we found that the HSA-SH content was higher (11-33%) than the total
      serum thiol content. The influence of fatty acids (FA) binding to HSA on this
      discrepancy was investigated in vitro (using fluorescence and CD spectroscopy and
      GC) and with HSA samples from diabetic (n=20) and control groups (n=17). HSA
      bound FA determine the selection of HSA molecules by CB and enhance reactivity
      and/or accessibility of the SH group. A high content of polyunsaturated FA
      (35.6%) leads to weaker binding of HSA molecules to CB. Rate constants of DTNB
      reaction with the SH group of HSA applied to a CB column, bound-HSA and unbound
      HSA fractions, were 4.8*10(-3), 21.6*10(-3), and 11.2*10(-3) s(-1), respectively.
      The HSA-SH group of diabetics is more reactive compared with control individuals
      (rate constants 20.9*10(-3)+/-4.4*10(-3) vs 12.9*10(-3)+/-2.6*10(-3) s(-1),
      P<0.05). Recovery values of the SH group obtained after chromatography of HSA
      with bound stearic acid ranged from 110 to 140%, while those for defatted HSA
      were from 98.5 to 101.7%. Thus, HSA-bound FA leads to an increase of HSA-SH
      content and a contribution to total serum thiols, which make the determination of
      the thiol group unreliable. 

PMID- 24316318
TI  - Anti-Candida activity of spent culture filtrate of Lactobacillus plantarum strain
      LR/14.
AB  - OBJECTIVES: This study was undertaken to understand the effect of antimicrobial
      compounds produced by an environmental isolate of lactic acid bacterium,
      Lactobacillus plantarum strain LR/14, on growth, viability and biofilm forming
      ability of the pathogenic yeast, Candida albicans SC5314 and to identify the mode
      of action of such compounds. MATERIAL AND METHODS: L. plantarum LR14 was grown at
      37 degrees C for 18 h in MRS broth. The spent culture filtrate (SCF) was
      collected by centrifugation and checked for anti-Candida activity. Live/dead
      staining followed by fluorescence microscopy was done to study the membrane
      damage. Increased membrane permeability was confirmed by measuring the release of
      ions and macromolecules (ATP) using atomic absorption spectrophotometer and
      luminometer, respectively. Effect on biofilm formation was quantified by MTT
      reduction assay. RESULTS: The viability of yeast cells was affected by SCF LR14
      treatment in a dose-dependent manner, exerting a fungicidal effect. The active
      compound was identified as a pH-dependent thermostable proteinaceous metabolite.
      The fungicidal activity was further confirmed by PI staining, suggesting
      compromised membrane as the cause of cell death. Leakage of intracellular
      contents such as, K+ ions and ATP, as a cause of its inhibitory action further
      confirmed the membrane disruption. Moreover, significant reduction in biofilm
      formation was also confirmed. CONCLUSIONS: SCF LR14 showed potent anti-Candida
      activity, affecting cell viability, membrane permeability, and biofilm formation
      and leading to cell death, thereby suggested a probable candidate as a natural
      therapeutic agent.

PMID- 24316319
TI  - The Mobile Team of Parasitology-Mycology, a medical entity for educational
      purposes to serve sick patients.
AB  - The Mobile Team of Parasitology-Mycology is a movable entity of the Parasitology
      Mycology laboratory of Tours University Hospital, France. In contrast to the
      usual prerogatives of biomedical laboratories, the Mobile Team of Parasitology
      Mycology is requested to intervene directly at bedside in various clinical
      departments, or even outside the hospital facility. Although its actions are of
      course primarily devoted to specialized diagnostic and therapeutic purposes, the
      Mobile Team also plays an important educational role in the medical training of
      undergraduate or graduate students. 

PMID- 24316320
TI  - Urinary metabolites of organophosphate flame retardants and their variability in
      pregnant women.
AB  - Organophosphate flame retardants (OPFRs) are commonly added to consumer products
      to reduce their flammability. Based on levels of OPFRs in indoor environments,
      human exposure is likely chronic and ubiquitous. Animal studies suggest that
      exposure to some OPFRs may result in adverse health impacts, particularly for
      Tris (1,3-dichloropropyl) phosphate (TDCPP); however, human data on the impacts
      of exposure to OPFRs are lacking. To design human studies, more information is
      needed on the stability of measured OPFRs in human samples over time. In this
      study, we sought to assess the degree of temporal variability of urinary TDCPP
      and triphenyl phosphate (TPP) metabolites throughout pregnancy in a cohort of
      women from central North Carolina. Eight pregnant women provided multiple urine
      samples: 3 during the 18th week of pregnancy, 1 during the 28th week, and 1
      shortly after the child's birth. Bis (1,3-dichloropropyl) phosphate (BDCPP) and
      diphenyl phosphate (DPP), the respective metabolites of TDCPP and TPP, were
      measured in urine samples using liquid chromatography-tandem mass spectrometry.
      BDCPP and DPP were each detected in 38 of 39 urine samples and were not normally
      distributed. Geometric mean BDCPP and DPP concentrations were 1.3ng/mL
      (interquartile range (IQR): 0.8, 2.7ng/mL) and 1.9ng/mL (IQR: 0.9, 3.5ng/mL),
      respectively. BDCPP and DPP were moderately to strongly reliable over one week
      (intraclass correlation coefficient (ICC)=0.5; 95% confidence interval (CI): 0.4,
      0.7 and ICC=0.7; 95% CI: 0.5, 0.8, respectively), and over the entire pregnancy
      (ICC=0.5 95% CI: 0.3, 0.7 and ICC=0.6; 95% CI: 0.4, 0.7, respectively). These
      data suggest that exposures to TDCPP and TPP are widespread and variable for
      pregnant women, and that a single measure of BDCPP or DPP, taken in the second
      trimester, likely captures information on the rank order of exposure throughout
      pregnancy. 

PMID- 24316322
TI  - Overexpression of complement C5 in endometriosis.

PMID- 24316321
TI  - Source attribution of personal exposure to airborne polycyclic aromatic
      hydrocarbon mixture using concurrent personal, indoor, and outdoor measurements.
AB  - OBJECTIVES: Relative importance of multiple indoor and outdoor venues on personal
      exposure concentrations to pro-carcinogenic polycyclic aromatic hydrocarbons (c
      PAHs) remains poorly understood. This is particularly challenging because many c
      PAHs share sources and occur as a complex mixture. Accurate and precise
      apportionment of personal exposure according to exposure venues could aid in the
      understanding of human health effects due to a given source. Here, we partitioned
      indoor and personal exposure concentrations to seven c-PAHs and pyrene according
      to the indoor- and outdoor-origins. METHODS: A simultaneous, integrated
      monitoring of personal, indoor and outdoor concentrations of nine PAHs was
      conducted in 75 homes for a consecutive 48-hour period across a two-year period
      in Krakow, Poland. Due to few known indoor sources for chrysene, we used this PAH
      species as a tracer for infiltration of outdoor PAHs. Personal and indoor
      concentrations of seven c-PAHs and pyrene were apportioned to home indoor, non
      home indoor and outdoor origins. RESULTS: Using Chrysenein/Chryseneout as proxy
      for an infiltration factor, Finf, infiltrated PAHs of outdoor origin are overall
      higher in concentration than those emitted from the indoor origin. Average
      contribution by the outdoor sources on B[a]A, B[b]F, and B[k]F were 92%, 79%, and
      78% across all seasons, respectively. In contrast, in homes where a household
      member smoked, average contributions by the outdoor sources on B[ghi]P, B[a]P,
      D[ah]A, and IP were lower (i.e., 67%, 65%, 67%, and 66%, respectively). Season
      averaged contributions by the outdoor sources on personal exposure to B[a]A,
      B[b]F, and B[k]F were 92%, 74%, and 77%, respectively. On the other hand, season
      averaged home indoor source contributions on personal exposure to B[a]A, B[b]F,
      and B[k]F were estimated at 6%, 15%, and 19%, respectively. Similar contributions
      by season-averaged home indoor sources on personal exposure were estimated at 28%
      for B[ghi]P, 31% for B[a]P, 25% for D[ah]A, and 28% for IP. CONCLUSION: Of the
      seven c-PAHs, B[a]A, B[b]F, and B[k]F are enriched in indoor and personal
      exposure concentrations from the outdoor coal-combustion. B[ghi]P, B[a]P,
      D[a,h]A, and IP, PAHs with some of the highest carcinogenic and mutagenic
      potencies, are considerably enriched by cigarette smoke in addition to the
      outdoor sources.

PMID- 24316324
TI  - Perception of GMOs by scientists and practitioners--the critical role of
      information flow about transgenic organisms.
AB  - The issue of GMOs arouses constantly strong emotions in public discourse. At the
      same time opinions of people particularly interested in this issues such as
      researchers, or potential users of this technology (e.g. farmers) are rarely
      subjected to analysis. Moreover, lack of knowledge about the flow of information
      "from the laboratory to the consumer" hinders implementation of any changes in
      this field. By using triangulation (combining quantitative and qualitative
      research and the use of various research tools) we explored the attitudes of
      Polish scientists, agricultural advisers and farmers (large scale agricultural
      producers) to the use of GMOs in the economy. On the basis of the performed
      research we diagnosed the effectiveness of information flow among these groups
      about transgenic organisms. 

PMID- 24316323
TI  - Enzyme catalysed production of sialylated human milk oligosaccharides and
      galactooligosaccharides by Trypanosoma cruzi trans-sialidase.
AB  - A Trypanosoma cruzi trans-sialidase (E.C. 3.2.1.18) was cloned into Pichia
      pastoris and expressed. The pH and temperature optimum of the enzyme was
      determined as pH 5.7 and 30 degrees C. Using casein glycomacropeptide (CGMP) and
      lactose as sialyl-donor and acceptor respectively, the optimal donor/acceptor
      ratio for the trans-sialidase catalysed 3'-sialyllactose production was found to
      be 1:4. Quantitative amounts of 3'-sialyllactose were produced from CGMP and
      lactose at a yield of 40mg/g CGMP. The 3'-sialyllactose obtained exerted a
      stimulatory effect on selected probiotic strains, including different
      Bifidobacterium strains in single culture fermentations. The trans-sialidase also
      catalysed the transfer of sialic acid from CGMP to galacto-oligosaccharides (GOS)
      and to the human milk oligosaccharide (HMO) backbone lacto-N-tetraose (LNT) to
      produce 3'-sialyl-GOS, including doubly sialylated GOS products, and 3'-sialyl
      LNT, respectively. This work thus provides proof of the concept of producing 3'
      sialyllactose and potentially other sialylated HMOs as well as sialylated GOS
      enzymatically by trans-sialidase activity, while at the same time providing
      valorisation of CGMP, a co-processing product from cheese manufacture. 

PMID- 24316325
TI  - Effectiveness of supported employment for veterans with spinal cord injury: 2
      year results.
AB  - OBJECTIVE: To examine if supported employment (SE) remains more effective than
      treatment as usual (TAU) in returning veterans to competitive employment after
      spinal cord injury (SCI) at 2-year follow-up. DESIGN: Prospective, randomized,
      controlled, multisite trial of SE versus TAU with 24 months of follow-up.
      SETTING: SCI centers. PARTICIPANTS: Subjects (N=201) were enrolled and completed
      baseline interviews. At interventional sites, subjects were randomized to SE
      (n=81) or TAU (n=76). At observational sites, 44 subjects were enrolled in a
      nonrandomized TAU condition. INTERVENTION: The intervention was a SE program
      called the SCI Vocational Integration Program, which followed the principles of
      the individual placement and support model of SE for persons with mental illness.
      MAIN OUTCOME MEASURES: Competitive employment in the community within 2 years.
      RESULTS: For the entire 2-year follow-up period, SE subjects were significantly
      more likely to achieve employment (30.8%; 95% confidence interval [CI], 21.8
      41.6) than either the TAU subjects at the intervention sites (10.5%; 95% CI, 5.2
      19.7; P<.001) or the TAU subjects at the observational sites (2.3%; 95% CI, 0.0
      12.9; P<.002). Most subjects who obtained competitive employment did so in year
      1, and the average time to first employment was about 17 weeks. CONCLUSIONS: SE
      was better than usual practices in improving employment outcomes for veterans
      with SCI across a 2-year follow-up period. Although SE continued to be superior
      to traditional practices over the entire study, the first year of participation
      in SE may represent a critical window for achieving employment after SCI.

PMID- 24316326
TI  - Changes in cognitive function from presurgery to 4 months postsurgery in
      individuals undergoing dysvascular amputation.
AB  - OBJECTIVE: To describe cognition among individuals with new amputations at 3 time
      points: presurgical, 6 weeks postamputation, and 4 months postamputation. DESIGN:
      Prospective cohort. SETTING: Medical centers. PARTICIPANTS: Referred sample
      Veterans who were primarily men (N=80) experiencing their first lower extremity
      amputation as a result of complications of diabetes mellitus or peripheral
      arterial disease. Patients were screened for the absence of gross cognitive
      impairment using the Short Portable Mental Status Questionnaire (SPMSQ). Of those
      87 individuals who were eligible, 64% enrolled; 29 were enrolled presurgically
      and have cognitive data for all 3 time points, and 58 were enrolled
      postamputation. Eighty of the 87 individuals enrolled by 6 weeks remained
      enrolled at 4 months. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Demographic and general health information, general mental status (SPMSQ), and 4
      brief, well-established neuropsychological measures. RESULTS: Most mean
      neuropsychological test scores fell in the low average or average range. For most
      participants, overall cognitive status improved from pre- to postsurgery and then
      remained stable between 6 weeks and 4 months. There were significant improvements
      between pre- and postsurgical test scores in verbal learning and memory, and
      these remained unchanged between 6 weeks and 4 months. Better 4 month cognitive
      performance was associated with higher perceived general health. CONCLUSIONS:
      Overall cognitive performance is poorest presurgically. Though there is
      improvement between pre- and postamputation, cognition appears generally stable
      between 6 weeks and 4 months.

PMID- 24316327
TI  - Symptoms of depression over time in adults with pediatric-onset spinal cord
      injury.
AB  - OBJECTIVE: To investigate the prevalence of depressive symptoms in adults with
      pediatric-onset spinal cord injury (SCI) and explore potential risk factors that
      may be associated with elevated symptoms. DESIGN: Longitudinal, cohort survey
      over a period of 2 to 9 years. Follow-up occurred approximately every year, a
      total of 868 interviews were conducted, and most participants contributed to at
      least 3 waves of data (72%; range, 2-8; mean, 4.34+/-2.16). SETTING: Community.
      PARTICIPANTS: Adults (N=214; 133 men; mean age at first interview, 29.52+/-5.21y;
      range, 24-42y) who sustained an SCI prior to age 19 (mean age at injury, 13.93+/
      4.37y; range, 0-18y). Participants tended to have complete injuries (71%) and
      tetraplegia (58%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Participants completed measures assessing psychosocial functioning, physical
      independence, participation, and depression at each time point. Multilevel growth
      modeling analyses were used to explore depression symptoms across time. RESULTS:
      Depression symptoms at initial status were typically minimal (3.07+/-.24; 95%
      confidence interval, 2.6-3.54) but fluctuated significantly over time (P<.01).
      Several factors emerged as significant predictors of depressive symptoms in the
      final model, including less community participation (P<.01), incomplete injury
      (P=.02), hazardous drinking (P=.02), bladder incontinence (P=.01), and pain
      (P=.03). Within individuals, as bowel accidents (P<.01) and pain increased
      (P<.01), depression scores increased; however, marriage resulted in decreases in
      depression scores for individuals (P=.02). CONCLUSIONS: These findings suggest
      that most patients with pediatric-onset SCI are psychologically resilient, but
      strategies to minimize secondary health complications and foster community
      participation and engagement should be considered.

PMID- 24316328
TI  - Bagging with CTD--a novel signature for the hierarchical prediction of secreted
      protein trafficking in eukaryotes.
AB  - Protein trafficking or protein sorting in eukaryotes is a complicated process and
      is carried out based on the information contained in the protein. Many methods
      reported prediction of the subcellular location of proteins from sequence
      information. However, most of these prediction methods use a flat structure or
      parallel architecture to perform prediction. In this work, we introduce ensemble
      classifiers with features that are extracted directly from full length protein
      sequences to predict locations in the protein-sorting pathway hierarchically.
      Sequence driven features, sequence mapped features and sequence autocorrelation
      features were tested with ensemble learners and their performances were compared.
      When evaluated by independent data testing, ensemble based-bagging algorithms
      with sequence feature composition, transition and distribution (CTD) successfully
      classified two datasets with accuracies greater than 90%. We compared our results
      with similar published methods, and our method equally performed with the others
      at two levels in the secreted pathway. This study shows that the feature CTD
      extracted from protein sequences is effective in capturing biological features
      among compartments in secreted pathways. 

PMID- 24316329
TI  - Identification of immunity-related genes in Arabidopsis and cassava using genomic
      data.
AB  - Recent advances in genomic and post-genomic technologies have provided the
      opportunity to generate a previously unimaginable amount of information. However,
      biological knowledge is still needed to improve the understanding of complex
      mechanisms such as plant immune responses. Better knowledge of this process could
      improve crop production and management. Here, we used holistic analysis to
      combine our own microarray and RNA-seq data with public genomic data from
      Arabidopsis and cassava in order to acquire biological knowledge about the
      relationships between proteins encoded by immunity-related genes (IRGs) and other
      genes. This approach was based on a kernel method adapted for the construction of
      gene networks. The obtained results allowed us to propose a list of new IRGs. A
      putative function in the immunity pathway was predicted for the new IRGs. The
      analysis of networks revealed that our predicted IRGs are either well documented
      or recognized in previous co-expression studies. In addition to robust
      relationships between IRGs, there is evidence suggesting that other cellular
      processes may be also strongly related to immunity. 

PMID- 24316330
TI  - Hands-on workshops as an effective means of learning advanced technologies
      including genomics, proteomics and bioinformatics.
AB  - Genomics and proteomics have emerged as key technologies in biomedical research,
      resulting in a surge of interest in training by investigators keen to incorporate
      these technologies into their research. At least two types of training can be
      envisioned in order to produce meaningful results, quality publications and
      successful grant applications: (1) immediate short-term training workshops and
      (2) long-term graduate education or visiting scientist programs. We aimed to fill
      the former need by providing a comprehensive hands-on training course in
      genomics, proteomics and informatics in a coherent, experimentally-based
      framework. This was accomplished through a National Heart, Lung, and Blood
      Institute (NHLBI)-sponsored 10-day Genomics and Proteomics Hands-on Workshop held
      at National Jewish Health (NJH) and the University of Colorado School of Medicine
      (UCD). The course content included comprehensive lectures and laboratories in
      mass spectrometry and genomics technologies, extensive hands-on experience with
      instrumentation and software, video demonstrations, optional workshops, online
      sessions, invited keynote speakers, and local and national guest faculty. Here we
      describe the detailed curriculum and present the results of short- and long-term
      evaluations from course attendees. Our educational program consistently received
      positive reviews from participants and had a substantial impact on grant writing
      and review, manuscript submissions and publications. 

PMID- 24316331
TI  - Pubertal timing after neonatal diethylstilbestrol exposure in female rats:
      neuroendocrine vs peripheral effects and additive role of prenatal food
      restriction.
AB  - We studied the effects of neonatal exposure to diethylstilbestrol (DES) on
      pubertal timing in female rats. We examined associated neuroendocrine changes and
      effects of prenatal food restriction. Age at vaginal opening was advanced after
      exposure to 10 MUg/kg/d of DES and delayed after 1 MUg/kg/d (subcutaneous
      injections). Using this lower dose, pulsatile GnRH secretion was slower at 25
      days of age. Both doses reduced KiSS1 mRNA levels at 15 days of age. Using
      functional Kisspeptin promoter assay, 1 or 10 MUM DES reduced or increased KISS1
      transcription, respectively. Leptin stimulatory effect on GnRH secretion in vitro
      (15 days of age) was reduced after prenatal food restriction and neonatal DES
      exposure (higher dose), both effects being cumulative. Thus, alterations in
      pubertal timing by DES neonatally are not unequivocally toward precocity, the
      level of exposure being critical. We provide evidence of neuroendocrine
      disruption and interaction with prenatal food availability.

PMID- 24316333
TI  - Use of bacteriophage particles displaying influenza virus hemagglutinin for the
      detection of hemagglutination-inhibition antibodies.
AB  - Bacteriophage lambda capsids provide a flexible molecular scaffold that can be
      engineered to display a wide range of exogenous proteins, including full-length
      viral glycoproteins produced in eukaryotic cells. One application for such
      particles lies in the detection of virus-specific antibodies, since they may
      obviate the need to work with infectious stocks of highly pathogenic or emerging
      viruses that can pose significant biosafety and biocontainment challenges.
      Bacteriophage lambda capsids were produced that displayed an insect-cell derived,
      recombinant H5 influenza virus hemagglutinin (HA) on their surface. The particles
      agglutinated red blood cells efficiently, in a manner that could be blocked using
      H5 HA-specific monoclonal antibodies. The particles were then used to develop a
      modified hemagglutinination-inhibition (HAI) assay, which successfully identified
      human sera with H5 HA-specific HAI activity. These results demonstrate the
      utility of HA-displaying bacteriophage capsids for the detection of influenza
      virus-specific HAI antibodies. 

PMID- 24316334
TI  - Stress inhibits psychomotor performance differently in simple and complex open
      field environments.
AB  - Stress affects psychomotor profiles and exploratory behavior in response to
      environmental features. Here we investigated psychomotor and exploratory patterns
      induced by stress in a simple open-field arena and a complex, multi-featured
      environment. Groups of rats underwent seven days of restraint stress or no-stress
      conditions and were individually tested in three versions of the ziggurat task
      (ZT) that varied according to environmental complexity. The hyperactivity of the
      hypothalamic-pituitary-adrenal (HPA) axis due to stress procedure was evaluated
      by the pre- and post-stress levels of circulating corticosterone (CORT).
      Horizontal activity, exploration, and motivation were measured by the number of
      fields entered, the time spent in the central fields, path length and speed, and
      stop duration. In addition, vertical exploratory behavior was measured by the
      times rats climbed onto ziggurats. Stress-induced psychomotor changes were
      indicated by reduced path length and path speed and increased duration of stops
      only within the complex arena of the ZT. Rats in stress groups also showed a
      significant decline in the vertical movements as measured by the number of
      climbing onto ziggurats. No stress-induced changes were revealed by the simple
      open-field arena. The exploratory patterns of stressed animals suggest
      psychomotor inhibition and reduced novelty-seeking behaviors in an environment
      dependent manner. Thus, multi-featured arenas that require complex behavioral
      strategies are ideally suited to reveal the inhibitory effects of stress on
      psychomotor capabilities in rodents. 

PMID- 24316335
TI  - Madelung's deformity.

PMID- 24316336
TI  - Hemophagocytic syndrome as the initial manifestation of systemic lupus
      erythematosus.
AB  - INTRODUCTION: Hemophagocytic syndrome (HS) occurs in autoimmune diseases and
      belongs to the hemophagocytic lymphohistiocytosis group of diseases. This paper
      describes the features of 2 patients with systemic lupus erythematosus (SLE) who
      presented HS as the initial clinical manifestation. CLINICAL OBSERVATIONS: Both
      patients had prolonged fever not associated to an infectious process and did not
      respond to broad-spectrum antibiotics. DISCUSSION: The diagnosis of HS secondary
      to SLE is complicated, because it has some features in common, but HS is
      characterized by hyperferritinemia, hipofibrinogemia, hypertriglyceridemia and a
      decrease in the erythrocyte sedimentation rate, unlike SLE. HS treatment when
      associated to SLE is not well established, but steroids and/or immunoglobulins
      are effective as the initial treatment, and in refractory cases, cyclosporine or
      cyclophosphamide may be associated. CONCLUSIONS: HS can be the initial
      manifestation of SLE and should be suspected in patients with organ enlargement,
      cytopenias, clotting disorders, liver disorders and prolonged fever unresponsive
      to antibiotics. Anakinra may be a treatment option in adult HS associated to SLE.

PMID- 24316337
TI  - TIM-family molecules in embryonic hematopoiesis: fetal liver TIM-4(lo) cells have
      myeloid potential.
AB  - Trans-membrane (or T cell) immunoglobulin and mucin (TIM) molecules are known
      regulators of immune response whose function in hematopoiesis is unknown.
      Earlier, we found that tim-1 and tim-4 are expressed by CD45(+) cells in the para
      aortic region of chicken embryo. Because the para-aortic region is a known site
      for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC)
      differentiation and expansion, we hypothesize that TIM molecules have a role in
      hematopoiesis. To study this role further, we analyzed TIM expression more
      precisely in chicken para-aortic region and mouse fetal liver hematopoietic
      cells. Additionally, we examined the hematopoietic potential of TIM-4(+) mouse
      fetal liver cells with a colony-forming assay. tim-1 gene expression was detected
      in chicken and mouse embryos in the aorta-gonads-mesonephros-region at the time
      of HSC emergence, whereas tim-3 mRNA was widely expressed in different tissues.
      tim-4 expression was restricted to fetal liver CD45(+)F4/80(+) cells. Moreover,
      two TIM-4(+) populations were distinguished: F4/80(hi)TIM-4(hi) and F4/80(lo)TIM
      4(lo). F4/80(hi)TIM-4(hi) cells had no hematopoietic potential and were
      morphologically similar to mature macrophages, suggesting that they are yolk sac
      derived macrophages. Instead, many of the F4/80(lo)TIM-4(lo) cells were c-kit(+)
      and Sca-1(+) and had primitive morphology and multilineage colony-forming
      ability. In addition, F4/80(lo)TIM-4(lo) cells included a considerable population
      expressing ER-MP12, a known marker for macrophage colony-forming cells and other
      myeloid progenitors. We conclude that TIM molecules are expressed in embryonic
      hematopoietic tissues in chicken and mouse and that in fetal liver, TIM-4 is
      expressed by myeloid progenitor cells. 

PMID- 24316338
TI  - PET imaging and biodistribution analysis of the effects of succinylated gelatin
      combined with L-lysine on renal uptake and retention of 64Cu-cyclam-RAFT-c(-RGDfK
      )4 in vivo.
AB  - (64)Cu-cyclam-RAFT-c(-RGDfK-)4, an alphaVbeta3 integrin-targeting tetrameric
      cyclic RGD peptide probe, is a potential theranostic compound for positron
      emission tomography (PET) of tumor angiogenesis and for internal radiotherapy
      owing to the multiple decay modes of (64)Cu. Since kidneys are dose-limiting
      organs in internal radiotherapy, we aimed to reduce the renal accumulation of
      (64)Cu-cyclam-RAFT-c(-RGDfK-)4 by co-injection with Gelofusine (GF), a
      succinylated gelatin solution, and/or L-lysine (Lys), and to explore, for the
      first time, the related mechanisms using the noninvasive and quantitative PET
      imaging technology. Biodistribution assays, dynamic and static PET scans, and
      metabolism studies with radio-thin-layer chromatography (radio-TLC) were
      performed in healthy or alphaVbeta3-positive tumor-bearing mice. In the results,
      co-injection with GF markedly reduced the renal uptake and slightly increased the
      tumor uptake of (64)Cu-cyclam-RAFT-c(-RGDfK-)4. L-Lysine alone had no effect on
      the probe biodistribution, but the combined use of Lys and GF tended to enhance
      the effect of GF. Dynamic PET and metabolite analysis by radio-TLC highly
      revealed that GF blocks the renal reabsorption of (64)Cu-cyclam-RAFT-c(-RGDfK-)4,
      but does not interfere with its metabolism and excretion. In conclusion,
      administration of GF and Lys is a useful strategy for kidney protection in (64)Cu
      cyclam-RAFT-c(-RGDfK-)4-based internal radiotherapy.

PMID- 24316339
TI  - Combination cytotoxicity of backbone degradable HPMA copolymer gemcitabine and
      platinum conjugates toward human ovarian carcinoma cells.
AB  - Multiblock, backbone degradable HPMA copolymer-drug conjugates containing
      gemcitabine and DACH platinum (mP-GEM and mP-DACH Pt), respectively were
      synthesized by reversible addition-fragmentation chain transfer (RAFT)
      polymerization and subsequent chain extension by click chemistry. Using
      combination index analysis, the cytotoxicities of the two multiblock conjugates,
      as single agent and in combination, were evaluated in vitro in A2780 human
      ovarian cancer cells, with free drugs as controls. The greatest synergistic
      cytotoxic effect was observed when A2780 cells were sequentially exposed to mP
      GEM for 24h and mP-DACH Pt for 48h. In addition, mechanistic studies support the
      rationale of the synergy between mP-GEM and mP-DACH Pt: mP-GEM pretreatment was
      able to enhance the platinum-DNA adduct accumulation and inhibit cell
      proliferation to a higher extent than single mP-DACH Pt treatment. These
      observations are useful for the development of combination macromolecular
      therapeutics for ovarian cancer based on the second-generation backbone
      degradable HPMA copolymers. 

PMID- 24316340
TI  - Transport mechanism of doxorubicin loaded chitosan based nanogels across
      intestinal epithelium.
AB  - Chitosan/carboxymethyl chitosan nanogels (CS/CMCS-NGs) could enhance the oral
      bioavailability of doxorubicin hydrochloride (DOX). To identify the mechanisms
      that support this recent observation, different transport pathways of CS/CMCS-NGs
      through the small intestine were studied in this work. Transcellular mechanisms
      were investigated in the presence of different inhibitors of protein-mediated
      endocytosis. A reduction of 52.32+/-18% of drug transport was found when clathrin
      mediated endocytosis was inhibited, which demonstrated that clathrin-mediated
      endocytosis played an important role in the transcellular transport of
      DOX:CS/CMCS-NGs. The paracellular transport results showed that CMCS in NGs could
      produce a transient and reversible enhancement of paracellular permeability by
      depriving Ca(2+) from adherens junctions, whose efficacy as an absorption
      enhancer was about 1.7-3.3 folds higher than CS in NGs in GI tract. Finally, in
      vivo experiment showed that the transport capacity of DOX:CS/CMCS-NGs was
      significantly inhibited by extra added Ca(2+), which confirmed that the higher
      capacity to binding Ca(2+) of CS/CMCS-NGs was beneficial for transport of DOX. 

PMID- 24316341
TI  - Linking evidence to treatment for denture stomatitis: a meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVES: The aim of this meta-analysis was to compare the efficacy of
      antifungal therapy with any other alternative methods used for the treatment of
      denture stomatitis. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register
      of Controlled Trials and the Cochrane Database of Systematic Reviews were
      searched, complemented by hand searching, until the first week of January 2013.
      STUDY SELECTION: Included studies consisted of randomized clinical trials
      published in English or French, which compared antifungals with any other
      alternative or placebo, used for the treatment of denture stomatitis. The
      remission of clinical signs of denture stomatitis, and the reduction in Candida
      colony counts were considered as the clinical and microbiological outcomes,
      respectively. Random effects models were used to conduct the statistical
      analyses. RESULTS: From 233 identified articles, a total of 15 manuscripts on 14
      randomized controlled trials were included in systematic review and 8 in the meta
      analysis. No statistically significant difference between antifungal treatment
      and disinfection methods was found for both clinical (OR=0.7; 95% CI: 0.32-1.36;
      Z=-1.14; p=0.256) and microbiological (OR=0.8; 95% CI: 0.26-2.5; Z=-0.35;
      p=0.724) outcomes. The meta-analysis showed a statistically significant
      difference between an antifungal and a placebo for the microbiological outcome
      (OR=0.32; 95% CI: 0.12-0.89; Z=-2.2; p=0.028), favouring the antifungals.
      However, there was no statistically significant difference between antifungal and
      placebo for the clinical outcome (OR=0.2; 95% CI: 0.04-1.04; Z=-1.9; p=0.056).
      CONCLUSIONS: Disinfection agents, antiseptic mouthwashes, natural substances with
      antimicrobial properties, microwave disinfection and photodynamic therapy could
      be suggested as an adjunct or alternative to antifungal medications in the
      treatment of denture stomatitis.

PMID- 24316342
TI  - Changes in oral health related quality of life after dental bleaching in a double
      blind randomized clinical trial.
AB  - OBJECTIVES: This study aimed to assess changes in oral health-related quality of
      life (OHRQoL) in individuals enroled in a double-blind randomized clinical trial
      conducted to evaluate the efficacy and safety of two carbamide peroxide
      concentrations used in at-home vital bleaching in the city of Pelotas, Southern
      Brazil. METHODS: Ninety-two volunteers with a shade mean of C1 or darker for the
      six maxillary anterior teeth were randomized into two balanced groups (n=46)
      according to bleaching agent concentration: 10% or 16% carbamide peroxide. The
      patients were instructed to use the whitening agent in a tray for 2h once a day
      for three weeks. To assess changes in OHRQoL, participants completed the oral
      impact on daily performance (OIDP) at the start and one week after the completion
      of treatment. Because there was no difference with regard to whitening effect or
      tooth sensitivity during or after treatment the two groups were merged for the
      analyses of the current article. Before-and-after changes in OIDP scores were
      assessed by chi-square and McNemar tests (p<0.05). RESULTS: Mean pre- and post
      treatment OIDP scores varied from 0.42 to 0.60. When the frequency of impacts for
      different activities were compared, there was an increase in difficulty in
      cleaning teeth (p=0.02) and a significant reduction in smiling and showing teeth
      with embarrassment (p=0.03). Regarding the symptoms and main oral conditions that
      generated impact, there was higher number of participants reporting pain (p=0.05)
      after treatment. In opposite, significant decrease was observed in individuals
      reporting being unhappy with their appearance (p=0.03). On the contrary, it was
      showed a decrease in impacts resulting from dental colour was observed after
      bleaching (p=0.03). CONCLUSION: Quality of life is complex and encompasses
      different domains. Although positive impact of the dental bleaching was detected,
      with patients showing more their teeth without embarrassment, difficult in dental
      hygiene and pain resulting from the treatment were also reported, and this can
      negatively impact daily performances. Dentists must consider these aspects when
      performing aesthetics procedures.

PMID- 24316343
TI  - Effect of pretreatments on the metal-ceramic bonding strength of a Pd-Ag alloy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy of surface
      treatments on the bonding properties between a metal and ceramic. METHODS: Sixty
      metal specimens were divided equally into four groups of 15 samples each. These
      groups received different treatments (Gr1: 250MUm Al2O3+preoxidation; Gr2: 250MUm
      Al2O3+degassing; Gr3: 120MUm Al2O3+preoxidation; Gr4: 120MUm Al2O3+degassing).
      Bond strengths were evaluated using a three-point bending test. The results were
      analyzed using 2-way ANOVA and Tukey's test. Scanning electron microscopy and
      energy dispersive spectroscopy were used to observe the microscopic features,
      elemental compositions and distributions, and diffusion in the specimens.
      Mechanical profiler was used to measure the roughness of metal surface. RESULTS:
      The bond strengths of the four groups ranged from 45.00+/-3.63MPa to 51.61+/
      5.91MPa, with significant differences (P<.05). The specimen that received the
      pretreatment of 250MUm Al2O3 air-particle abrasion+degassing had the highest bond
      strength. Heating under different oxygen partial pressures caused the final Pd-Ag
      alloys to have varying degrees of internal oxidation and different quantities of
      metallic nodules. None of the elements in either the ceramic or the Pd-Ag alloy
      layer diffused into the other layer. CONCLUSIONS: The metal-ceramic specimen
      subjected to air-particle abrasion with 250MUm Al2O3 and degassed before
      porcelain firing had significantly higher bond strength than specimens treated
      differently.

PMID- 24316345
TI  - R (-)-ketamine shows greater potency and longer lasting antidepressant effects
      than S (+)-ketamine.
AB  - The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is one of the most
      attractive antidepressants for treatment-resistant major depressive disorder
      (MDD). Ketamine (or RS (+/-)-ketamine) is a racemic mixture containing equal
      parts of R (-)-ketamine and S (+)-ketamine. In this study, we examined the
      effects of R- and S-ketamine on depression-like behavior in juvenile mice after
      neonatal dexamethasone (DEX) exposure. In the tail suspension test (TST) and
      forced swimming test (FST), both isomers of ketamine significantly attenuated the
      increase in immobility time, seen in DEX-treated juvenile mice at 27 and 29 h
      respectively, after ketamine injections. In the 1% sucrose preference test (SPT),
      both isomers significantly attenuated the reduced preference for 1% sucrose
      consumption in DEX-treated juvenile mice, 48 h after a ketamine injection.
      Interestingly, when immobility times were tested by the TST and FST at day 7, R
      ketamine, but not S-ketamine, significantly lowered the increases in immobility
      seen in DEX-treated juvenile mice. This study shows that a single dose of R
      ketamine produced rapid and long-lasting antidepressant effects in juvenile mice
      exposed neonatally to DEX. Therefore, R-ketamine appears to be a potent and safe
      antidepressant relative to S-ketamine, since R-ketamine may be free of
      psychotomimetic side effects.

PMID- 24316344
TI  - The inhibition effect of non-protein thiols on dentinal matrix metalloproteinase
      activity and HEMA cytotoxicity.
AB  - OBJECTIVES: Phosphoric acid (PA) etching used in etch-and-rinse adhesives is
      known to activate host-derived dentinal matrix-metalloproteinases (MMPs) and
      increase dentinal permeability. These two phenomena will result, respectively; in
      degradation of dentine-adhesive bond and leaching of some monomers especially 2
      hydroxyethyl methacrylate (HEMA) into the pulp that would negatively affect the
      viability of pulpal cells. This study is the first to investigate the inhibitory
      effect of non-protein thiols (NPSH); namely reduced glutathione (GSH) and N
      acetylcysteine (NAC) on dentinal MMPs and compare their effects on HEMA
      cytotoxicity. METHODS: Dentine powder was prepared from human teeth,
      demineralized with 1% PA and then treated with 2% GSH, 2% NAC or 2% chlorhexidine
      (CHX). Zymographic analysis of extracted proteins was performed. To evaluate the
      effect of GSH, NAC and CHX on HEMA cytotoxicity, solutions of these compounds
      were prepared with or without HEMA and rat pulpal cells were treated with the
      tested solutions for (6 and 24h). Cells viability was measured by means of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytotoxicity
      data were analysed by one-way ANOVA and Tukey post hoc tests (p<0.05). RESULTS:
      The inhibitory effect of GSH and NAC on dentinal MMPs was confirmed. GSH showed
      similar effectiveness to NAC regarding HEMA cytotoxicity inhibition. CONCLUSION:
      NPSH were effective to inhibit dentinal MMPs and HEMA cytotoxicity. CLINICAL
      SIGNIFICANCE: The tested properties of NPSH provide promising clinical use of
      these agents which would enhance dentine-bond durability and decrease post
      operative sensitivity.

PMID- 24316346
TI  - MDMA decreases the effects of simulated social rejection.
AB  - 3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social
      feelings and decreases the ability to detect social threat in faces, but its
      effects on experiences of social acceptance and rejection have not been
      determined. We examined how an acute dose of MDMA affects subjective and
      autonomic responses to simulated social acceptance and rejection. We predicted
      that MDMA would decrease subjective responses to rejection. On an exploratory
      basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA),
      a measure of parasympathetic cardiac control often thought to index social
      engagement and emotional regulation. Over three sessions, healthy adult
      volunteers with previous MDMA experience (N=36) received capsules containing
      placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind
      conditions. During expected peak drug effect, participants played two rounds of a
      virtual social simulation task called "Cyberball" during which they experienced
      acceptance in one round and rejection in the other. During the task we also
      obtained electrocardiograms (ECGs), from which we calculated RSA. After each
      round, participants answered questionnaires about their mood and self-esteem. As
      predicted, MDMA decreased the effect of simulated social rejection on self
      reported mood and self-esteem and decreased perceived intensity of rejection,
      measured as the percent of ball tosses participants reported receiving.
      Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to
      placebo. Our finding that MDMA decreases perceptions of rejection in simulated
      social situations extends previous results indicating that MDMA reduces
      perception of social threat in faces. Together these findings suggest a cognitive
      mechanism by which MDMA might produce pro-social behavior and feelings and how
      the drug might function as an adjunct to psychotherapy. These phenomena merit
      further study in non-simulated social environments.

PMID- 24316347
TI  - Memory interfering effects of chlordiazepoxide on consummatory successive
      negative contrast.
AB  - Long-Evans rats downshifted from 32% to 4% sucrose solution exhibit lower
      consummatory behavior during downshift trials than rats exposed only to 4%
      sucrose. In Experiment 1, this effect, called consummatory successive negative
      contrast (cSNC), was attenuated by administration of the benzodiazepine
      anxiolytic chlordiazepoxide (CDP, 5mg/kg, ip) before the second downshift trial
      (Trial 12), but was not affected when CDP was administered before the first
      downshift trial (Trial 11). In Experiment 2, CDP administered after Trial 11
      actually enhanced the cSNC effect on Trial 12. This posttrial effect of CDP was
      reduced by delayed administration (Experiment 3). This CDP effect was not present
      in the absence of incentive downshift (Experiments 4-5), or when animals were
      tested with the preshift incentive (Experiment 6) or after complete recovery from
      cSNC (Experiment 7). The posttrial CDP effect was observed after an 8-day
      interval between Trials 11 and 12 (Experiment 8) and when administered after
      Trial 12, rather than Trial 11 (Experiment 9). Experiment 10 extended the effect
      to Wistar rats. Because CDP is a memory interfering drug, it was hypothesized
      that its posttrial administration interferes with the consolidation of the memory
      of the downshifted incentive, thus prolonging the mismatch between expected (32%
      sucrose) and obtained (4% sucrose) incentives that leads to the cSNC effect. 

PMID- 24316348
TI  - Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant
      effects and behavioral sensitization in mice.
AB  - It has been demonstrated that a prolonged period (48 h) of paradoxical sleep
      deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization,
      an animal model of addiction-related neuroadaptations. In the present study, we
      examined the effects of an acute short-term deprivation of total sleep (TSD) (6h)
      on AMP-induced behavioral sensitization in mice and compared them to the effects
      of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD
      (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms
      method) for 6 h. Immediately after the sleep deprivation period, mice were tested
      in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven
      days later, to assess behavioral sensitization, all of the mice received a
      challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10
      min. Total, peripheral, and central locomotion, and grooming duration were
      measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute
      injection of AMP and this effect was due to an increased locomotion in the
      central squares of the apparatus. Similarly, TSD facilitated the development of
      AMP-induced sensitization, but only in the central locomotion parameter. The data
      indicate that an acute period of TSD may exacerbate the behavioral effects of AMP
      in mice. Because sleep architecture is composed of paradoxical and slow wave
      sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or
      sensitization, our data suggest that the deprivation of slow wave sleep plays a
      critical role in the mechanisms that underlie the potentiating effects of TSD on
      both the acute and sensitized addiction-related responses to AMP.

PMID- 24316349
TI  - A mouse model mimicking human first night effect for the evaluation of hypnotics.
AB  - In humans, a first night effect (FNE) is characterized by increased sleep latency
      and decreased total sleep time in an unfamiliar environment, but the mechanism
      and treatment options for this universally experienced acute insomnia are
      unclear. We continuously recorded electroencephalography (EEG) and electromyogram
      (EMG) and measured plasma corticosterone levels to develop a mouse FNE model by
      inducing acute insomnia in mice that have been placed in unfamiliar cage
      environments. The sleep latency of mice 'moved to clean cages' (MCC) was longer
      than that for mice 'moved to dirty ones' (MDC). As compared to MDC mice, MCC mice
      showed stronger decreases in the amount of non-rapid eye movement (non-REM, NREM)
      and REM sleep, with a lower power density of NREM sleep, increased fragmentation
      and decreased stage transitions from NREM sleep to wake, and higher variation in
      plasma corticosterone levels. Treatment of MCC mice with zolpidem, diazepam,
      raclopride, pyrilamine, except SCH23390 shortened NREM sleep latency. In
      addition, zolpidem significantly increased NREM and REM sleep with the increase
      in slow wave activity (1.00-2.75 Hz), while raclopride significantly increased
      NREM and REM sleep without changing the EEG power density in MCC mice, whereas
      diazepam increased sleep with a drastic decrease in power density of the
      frequency band between 1.00 and 4.00 Hz, diazepam also increased the frequency
      band between 9.75 and 24.75 Hz during NREM sleep. These results indicate that a
      MCC mouse can mimic a FNE phenotype of humans and that zolpidem and raclopride
      may be useful drugs to prevent acute insomnia, including FNE.

PMID- 24316350
TI  - [Preliminary results of whole breast helical tomotherapy with simultaneous
      integrated boost in the adjuvant treatment of breast cancer].
AB  - PURPOSE: To evaluate the dosimetry and acute toxicity of helical tomotherapy for
      locoregional irradiation of patients after breast-conserving surgery. PATIENTS
      AND METHODS: Twenty breast cancer patients with breast-conserving surgery treated
      by helical tomotherapy have been studied. The median age was 49 (min: 25, max:
      69). The whole breast, tumour bed and lymph nodes were prescribed 52.2 Gy, 63.8
      Gy and 50.4 Gy, all in 29 fractions. The dose per fraction was 2.2 Gy to the
      boost, 1.8 Gy to the breast and 1.74 Gy to the lymph node volumes. The
      reproducibility was analysed by recording the daily shifts in x, y and z
      directions and roll rotation. All toxicities were described using the Common
      Terminology Criteria for Adverse Effects v3.0. RESULTS: Twenty-two tumours were
      irradiated. Six-eight percent were located in the inner quadrant. In 90 % of
      patients supraclavicular and internal mammary nodes were treated. The coverage of
      planning target volumes (PTV) was as follows: PTV boost: V107 = 0.3 % +/- 0.5 SD,
      V95 = 98.4 % +/- 1.9 SD; PTV breast: -V107 = 7.8 % +/- 17.3 SD, V95 = 96.8 % +/-
      2.2 SD; PTV LN: V107 = 2.5 % +/- 4.2 SD, V95 = 92.7 % +/- 13.2 SD. The mean V20
      of the homolateral lung was 18.9 % +/- 3.5 SD. For left side lesion, the mean V30
      of the heart was 0.9 % +/- 0.8 SD. The mean V5 was: V5 homolateral lung: 73.1 %
      +/- 11.8 ET, controlateral lung: 38.9 % +/- 21, heart (left side breast): 57.3 %
      +/- 21, controlateral breast: 15.5 % +/- 9.6. Median shifts were as follow: x
      axis -0.04 mm (IC 95: -0.4 +0.38), y-axis -0.37 mm +/- 5.51 (IC 95: -0.88 +0.14),
      z-axis 2.90 mm +/- 5.42 (IC 95:+2.4+3.4) and roll rotation 0.22 +/- 1.10 (IC 95: 
      0.1+0.32). The treatment tolerance was acceptable with 1 definitive interruption
      couple of fractions before the end and 3 temporal interruptions for skin
      toxicity. No grade 3 or 4 toxicity. Ninety-five percent of patients experienced
      skin toxicity: 45 % grade 2. There were 3 cases of oesophagitis. The median
      follow-up of presented series is 9.7 months and all of the patients are free of
      disease without any residual early or late toxicity. CONCLUSIONS: Helical
      tomotherapy can achieve full target coverage while protected to the heart and
      ipsilateral lung. This treatment was well tolerated and reproducible. However,
      the low doses to normal tissue volumes need to be reduced in future studies.

PMID- 24316351
TI  - [Localized primary bone lymphoma: about four cases].
AB  - PURPOSE: To study epidemiological, clinical, pathological anatomy and therapeutic
      results of localized primary bone lymphoma. PATIENTS AND METHODS: Between
      February 1993 and February 2013, four patients were treated for localized primary
      bone lymphoma in Sfax's hospitals (Tunisia). Treatment was decided regarding to
      the age of the patient, his performance status, stage of the disease, lactate
      dehydrogenase (LDH) and socio-economical conditions of the patient. The
      therapeutic evaluation was done after chemotherapy and after radiotherapy. There
      was a clinical, biological and radiological follow-up. RESULTS: The mean age was
      59.5 years. The sex-ratio was 3. Bone localizations were clavicula, femur,
      humerus and mandibula. All patients had stage I large cell B lymphoma. In 3
      cases, imaging showed osteolytic lesions with cortical destruction and extension
      to soft tissues. One patient had a fracture of the humerus. The treatment
      consisted in chemotherapy followed by radiotherapy. Three patients were alive
      with complete remission after a mean follow-up of 76 months. CONCLUSION: The
      treatment of primary bone lymphoma is based on a combination of chemotherapy
      (with or without anti-CD20) and radiotherapy. The prognosis is excellent when it
      is localized.

PMID- 24316352
TI  - Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as
      SARS-CoV 3C-like protease inhibitors.
AB  - The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and
      strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains
      a chymotrypsin-like main protease analogous to that of the main picornavirus
      protease, 3CL(pro). 3CL(pro) plays a pivotal role in the viral replication cycle
      and is a potential target for SARS inhibitor development. A series of isatin
      derivatives as possible SARS-CoV 3CL(pro) inhibitors was designed, synthesized,
      and evaluated by in vitro protease assay using fluorogenic substrate peptide, in
      which several showed potent inhibition against the 3CL(pro). Structure-activity
      relationship was analyzed, and possible binding interaction modes were proposed
      by molecular docking studies. Among all compounds, 8k1 showed most potent
      inhibitory activity against 3CL(pro) (IC50=1.04 MUM). These results indicated
      that these inhibitors could be potentially developed into anti-SARS drugs.

PMID- 24316353
TI  - Lipoic acid analogs with enhanced pharmacological activity.
AB  - Lipoic acid (1,2-dithiolane-3-pentanoic acid) is a pharmacophore with unique
      antioxidant and cytoprotective properties. We synthesized a library based upon
      the condensation of natural and unnatural amino acids with the carboxylic acid
      moiety of lipoic acid. SAR studies were conducted using a cardiac ischemia
      reperfusion animal model. Cytoprotective efficacy was associated with the R
      enantiomer of the dithiolane. Potency of library compounds was dictated by the
      acidic strength of the adduct. alpha-N-[(R)-1,2-dithiolane-3-pentanoyl]-L
      glutamyl-L-alanine, designated CMX-2043, was chosen for further pharmacologic
      evaluation.

PMID- 24316354
TI  - Analysis of microRNA and mRNA expression profiles highlights alterations in
      modulation of the MAPK pathway under octanal exposure.
AB  - Previous environmental microRNA (miRNA) studies have investigated a limited
      number of candidate miRNAs and have not evaluated functional effects on gene
      expression. In this study, we aimed to identify octanal (OC)-sensitive miRNAs and
      to characterize the relationships between miRNAs and expression of candidate
      genes involved in OC-induced toxicity. Microarray analysis identified 15 miRNAs
      that were differentially expressed in OC-exposed A549 human alveolar cells.
      Integrated analyses of miRNA and mRNA expression profiles identified significant
      miRNA-mRNA anti-correlations. GO analysis of 101 putative target genes showed
      that the biological category 'MAPK signaling pathway' was prominently annotated.
      Moreover, we detected increased phosphorylation of p38 MAPK in the OC-exposed
      group. By integrating the transcriptome and microRNAome, we provide evidence that
      OC can affect MAPK-induced toxicity signaling. Therefore, this study demonstrates
      the added value of an integrated miRNA-mRNA approach for identifying molecular
      events induced by environmental pollutants in an in vitro human model. 

PMID- 24316355
TI  - Using isotopically-coded hydrogen peroxide as a surface modification reagent for
      the structural characterization of prion protein aggregates.
AB  - The conversion of the cellular prion protein (PrP(C)) into aggregated beta
      oligomeric (PrP(beta)) and fibril (PrP(Sc)) forms is the central element in the
      development of prion diseases. Here we report the first use of isotopically-coded
      hydrogen peroxide surface modification combined with mass spectrometry (MS) for
      the differential characterization of PrP(C) and PrP(beta). (16)O and (18)O
      hydrogen peroxide were used to oxidize methionine and tryptophan residues in
      PrP(C) and PrP(beta), allowing for the relative quantitation of the extent of
      modification of each form of the prion protein. After modification with either
      light or heavy forms of hydrogen peroxide (H2(16)O2 and H2(18)O2), the PrP(C) and
      PrP(beta) forms of the protein were then combined, digested with trypsin, and
      analysed by LC-MS. The (18)O/(16)O signal intensity ratios were used to determine
      the relative levels of oxidation of specific amino acids in the PrP(C) and
      PrP(beta) forms. Using this approach we have detected several residues that are
      differentially-oxidized between the native and beta-oligomeric prion forms,
      allowing determination of the regions of PrP(C) involved in the formation of
      PrP(beta) aggregates. Modification of these residues in the beta-oligomeric form
      is compatible with a flip of the beta1-H1-beta2 loop away from amphipathic
      helices 2 and 3 during conversion. BIOLOGICAL SIGNIFICANCE: Surface modification
      using isotopically-coded hydrogen peroxide has allowed quantitative comparison of
      the exposure of methionine and tryptophan residues in PrP(C) and PrP(beta) forms
      of prion protein. Detected changes in surface exposure of a number of residues
      have indicated portions of the PrP structure which undergo conformational
      transition upon conversion. This article is part of a Special Issue entitled: Can
      Proteomics Fill the Gap Between Genomics and Phenotypes?

PMID- 24316356
TI  - Enzyme linked immuno mass spectrometric assay (ELIMSA).
AB  - A new technology termed ELIMSA combines the specificity and enzymatic
      amplification of Enzyme Linked Immunosorbent assay (ELISA) with the sensitivity
      and flexibility of mass spectrometry (MS). At present, substrates for the
      reporter enzymes horseradish peroxidase (HRP) or alkaline phosphatase (AP) yield
      colored, fluorescent or luminescent products. The central concept of ELIMSA is
      that the reporter enzymes HRP and AP yield products that ionize efficiently with
      a high signal to noise ratio that can be measured by mass spectrometry. The
      reporter enzymes HRP or AP may be covalently attached to a specific detection
      probe such as a protein or an antibody to bind their target analyte and then
      catalyze the rapid production of ionizable, small-molecules. The use of mass
      spectrometry to measure small molecule products may commonly reach femto to
      picomol amounts on the column with high signal to noise ratio. Mass spectrometry
      combined with the enzyme amplification in ELISA provides absolute sensitivity to
      detect attomol of PSA and was comparable to, or more sensitive, than radio immune
      assays and electrochemical detectors but with only existing reagents and
      equipment. ELIMSA permits monitoring of multiple substrates and products and
      provides comparison to absolute standards. BIOLOGICAL SIGNIFICANCE: There is an
      urgent need to detect and quantify low abundance proteins such as hormones,
      chemokines, cytokines, and others that exist at attomolar concentrations under
      physiological conditions by ELIMSA. A sensitive method for the quantification of
      immunological assays is obtained by applying mass spectrometry to detect the
      products of the alkaline phosphatase (AP) and horseradish peroxidase (HRP) enzyme
      reactions. There are many molecules from human subjects or micro-organisms that
      are of great importance to medicine, industry, nutrition or the environment that
      need to be repeatedly analyzed and are often near to, or beyond, the edge of
      existing analytical technology. The presence of molecules in biological samples,
      industrial products or the environment may be detected by probes that bind to the
      target analyte. Combining the reporter enzymes from ELISA with sensitive liquid
      chromatography (LC), electrospray ionization (ESI) and tandem mass spectrometry
      (MS/MS) will permit the sensitive detection and quantification of the molecular
      probes by Enzyme Linked Immuno Mass Spectrometric Assay (ELIMSA). The flexibility
      and sensitivity of mass spectrometry to measure large numbers of compounds
      simultaneously should permit the quantification of multiple ELIMSA reactions at
      separate mass-to-charge (m/z) ratios. Hence ELIMSA and it variants should permit
      the rapid and simple detection and quantification of many molecules over the
      complete range of biologically important concentrations without the use of
      radiolabels using only existing antibodies, reagents and instruments. Antibodies
      coupled to reporter enzymes that are widely used in biomedical and environmental
      applications can now be detected and quantified using ultra sensitive mass
      spectrometry to create a sensitive and flexible ELIMSA system. Absolute standards
      of analytes or enzyme product may serve as a reference.

PMID- 24316357
TI  - Proteomic analysis of rat proximal tubule cells following stretch-induced
      apoptosis in an in vitro model of kidney obstruction.
AB  - Urinary tract obstruction (UTO) is a commonly noted disorder on prenatal
      ultrasound that has the potential to lead to permanent loss of renal function. To
      study the molecular processes of the disease, an in vitro model has been
      developed which involves mechanical stretch of proximal tubule cells grown on
      flexible plates which mimics the physiological conditions during UTO. This study
      employs a one dimensional SDS-PAGE fractionation procedure, followed by in-gel
      digest and LC-MS/MS analysis in a semi-quantitative experiment using spectral
      counting to relatively quantify changes in protein expression following the
      established model of UTO. Quantitative analysis shows 317 of the 1630 identified
      proteins express altered abundance, with 135 increased and 182 decreased in
      abundance as a result of stretch. Gene ontology (GO) and KEGG annotations
      implicate a number of physiological processes that have been previously shown in
      addition to some potentially novel processes in UTO. The quantitative proteomic
      analysis we performed here provides a more complete characterization of changes
      in protein abundance as a result of stretch than previous studies, and provides a
      number of previously undescribed proteins in proximal tubule cells that may play
      a role in UTO. BIOLOGICAL SIGNIFICANCE: Urinary tract obstruction (UTO) is a
      commonly noted abnormality on prenatal ultrasound that can either resolve
      spontaneously or require surgical intervention to prevent permanent renal damage
      or loss of function. While targeted studies of UTO have shown a number of
      pathological responses in proximal tubule cells, there are currently no large
      scale quantitative studies that aim to elucidate a global cellular response. This
      study uses a semi-quantitative approach and applies a well characterized model of
      UTO to determine a number of cellular processes affected by UTO simulation and
      identifies a number of proteins with altered abundance that have not been noted
      previously in UTO. This article is part of a Special Issue entitled: Can
      Proteomics Fill the Gap Between Genomics and Phenotypes?

PMID- 24316358
TI  - Investigating Aspergillus nidulans secretome during colonisation of cork cell
      walls.
AB  - Cork, the outer bark of Quercus suber, shows a unique compositional structure, a
      set of remarkable properties, including high recalcitrance. Cork colonisation by
      Ascomycota remains largely overlooked. Herein, Aspergillus nidulans secretome on
      cork was analysed (2DE). Proteomic data were further complemented by microscopic
      (SEM) and spectroscopic (ATR-FTIR) evaluation of the colonised substrate and by
      targeted analysis of lignin degradation compounds (UPLC-HRMS). Data showed that
      the fungus formed an intricate network of hyphae around the cork cell walls,
      which enabled polysaccharides and lignin superficial degradation, but probably
      not of suberin. The degradation of polysaccharides was suggested by the
      identification of few polysaccharide degrading enzymes (beta-glucosidases and
      endo-1,5-alpha-l-arabinosidase). Lignin degradation, which likely evolved
      throughout a Fenton-like mechanism relying on the activity of alcohol oxidases,
      was supported by the identification of small aromatic compounds (e.g. cinnamic
      acid and veratrylaldehyde) and of several putative high molecular weight lignin
      degradation products. In addition, cork recalcitrance was corroborated by the
      identification of several protein species which are associated with autolysis.
      Finally, stringent comparative proteomics revealed that A. nidulans colonisation
      of cork and wood share a common set of enzymatic mechanisms. However the higher
      polysaccharide accessibility in cork might explain the increase of beta
      glucosidase in cork secretome. BIOLOGICAL SIGNIFICANCE: Cork degradation by fungi
      remains largely overlook. Herein we aimed at understanding how A. nidulans
      colonise cork cell walls and how this relates to wood colonisation. To address
      this, the protein species consistently present in the secretome were analysed, as
      well as major alterations occurring in the substrate, including lignin
      degradation compounds being released. The obtained data demonstrate that this
      fungus has superficially attacked the cork cell walls apparently by using both
      enzymatic and Fenton-like reactions. Only a few polysaccharide degrading enzymes
      could be detected in the secretome which was dominated by protein species
      associated with autolysis. Lignin degradation was corroborated by the
      identification of some degradation products, but the suberin barrier in the cell
      wall remained virtually intact. Comparative proteomics revealed that cork and
      wood colonisation share a common set of enzymatic mechanisms.

PMID- 24316359
TI  - Proteomics quality and standard: from a regulatory perspective.
AB  - Proteomics has emerged as a rapidly expanding field dealing with large-scale
      protein analyses. It is anticipated that proteomics data will be increasingly
      submitted to the U.S. Food and Drug Administration (FDA) for biomarker
      qualification or in conjunction with applications for the approval of drugs,
      medical devices, and other FDA-regulated consumer products. To date, however, no
      established guideline has been available regarding the generation, submission and
      assessment of the quality of proteomics data that will be reviewed by regulatory
      agencies for decision making. Therefore, this commentary is aimed at provoking
      some thoughts and debates towards developing a framework which can guide future
      proteomics data submission. The ultimate goal is to establish quality control
      standards for proteomics data generation and evaluation, and to prepare
      government agencies such as the FDA to meet future obligations utilizing
      proteomics data to support regulatory decision. 

PMID- 24316360
TI  - Calcium channelopathies and Alzheimer's disease: insight into therapeutic success
      and failures.
AB  - Calcium ions are versatile and universal biological signaling factors that
      regulate numerous cellular processes ranging from cell fertilization, to neuronal
      plasticity that underlies learning and memory, to cell death. For these functions
      to be properly executed, calcium signaling requires precise regulation, and
      failure of this regulation may tip the scales from a signal for life to a signal
      for death. Disruptions in calcium channel function can generate complex multi
      system disorders collectively referred to as "calciumopathies" that can target
      essentially any cell type or organ. In this review, we focus on the multifaceted
      involvement of calcium signaling in the pathophysiology of Alzheimer's disease
      (AD), and summarize the various therapeutic options currently available to combat
      this disease. Detailing the series of disappointing AD clinical trial results on
      cognitive outcomes, we emphasize the urgency to design alternative therapeutic
      strategies if synaptic and memory functions are to be preserved. One such
      approach is to target early calcium channelopathies centrally linked to AD
      pathogenesis. 

PMID- 24316361
TI  - Plasmodium falciparum CENH3 is able to functionally complement Cse4p and its, C
      terminus is essential for centromere function.
AB  - The Plasmodium falciparum centromeric histone variant PfCENH3 has been shown to
      occupy a 4-4.5 kb region on each chromosome, but the experimental demonstration
      of its structure-function relationship remains unexplored. By functional
      complementation assays, we report that the C-terminus, specifically the CATD
      region within the HFD of PfCENH3 is essential in centromere function. Our studies
      also indicate that the PfCENH3 specific LLAL residues of the CATD region are
      required for centromere targeting and chromosome segregation. Histone H3 of P.
      falciparum is not found to complement Cse4p (the yeast homologue of CENH3). We
      also report the identification of PfCENP-C, another component of the inner
      kinetochore protein complex and its association with PfCENH3. These studies thus
      delineate the structural determinants of PfCENH3.

PMID- 24316362
TI  - Polypeptide-based combination of paclitaxel and cisplatin for enhanced
      chemotherapy efficacy and reduced side-effects.
AB  - A novel methoxy poly(ethylene glycol)-b-poly(l-glutamic acid)-b-poly(l
      phenylalanine) (mPEG-b-P(Glu)-b-P(Phe)) triblock copolymer was prepared and
      explored as a micelle carrier for the co-delivery of paclitaxel (PTX) and
      cisplatin (cis-diamminedichlo-platinum, CDDP). PTX and CDDP were loaded inside
      the hydrophobic P(Phe) inner core and chelated to the middle P(Glu) shell,
      respectively, while mPEG provided the outer corona for prolonged circulation. An
      in vitro release profile of the PTX+CDDP-loaded micelles showed that the CDDP
      chelation cross-link prevented an initial burst release of PTX. The PTX+CDDP
      loaded micelles exhibited a high synergism effect in the inhibition of A549 human
      lung cancer cell line proliferation over 72 h incubation. For the in vivo
      treatment of xenograft human lung tumor, the PTX+CDDP-loaded micelles displayed
      an obvious tumor inhibiting effect with a 83.1% tumor suppression rate (TSR%),
      which was significantly higher than that of a free drug combination or micelles
      with a single drug. In addition, more importantly, the enhanced anti-tumor
      efficacy of the PTX+CDDP-loaded micelles came with reduced side-effects. No
      obvious body weight loss occurred during the treatment of A549 tumor-bearing mice
      with the PTX+CDDP-loaded micelles. Thus, the polypeptide-based combination of PTX
      and CDDP may provide useful guidance for effective and safe cancer chemotherapy.

PMID- 24316363
TI  - Lysyl oxidase-mediated collagen crosslinks may be assessed as markers of
      functional properties of tendon tissue formation.
AB  - Mechanical property elaboration of engineered tissues is often assumed on the
      basis of gene and protein characterizations, rather than mechanical testing.
      However, we recently demonstrated that mechanical properties are not consistently
      correlated with matrix content and organization during embryonic tissue
      development. Based on this, mechanical properties should be assessed
      independently during natural or engineered tissue formation. Unfortunately,
      mechanical testing is destructive, and thus alternative means of assessing these
      properties are desirable. In this study, we examined lysyl oxidase (LOX)-mediated
      crosslinks as markers for mechanical properties during embryonic tendon formation
      and the potential to detect them non-destructively. We used tandem mass
      spectrometry (LC-MS/MS) to quantify changes in hydroxylysyl pyridinoline (HP) and
      lysyl pyridinoline (LP) crosslink density in embryonic chick tendon as a function
      of developmental stage. In addition, we assessed a multiphoton imaging approach
      that exploits the natural fluorescence of HP and LP. With both techniques, we
      quantified crosslink density in normal and LOX-inhibited tendons, and correlated
      measurements with mechanical properties. HP and LP crosslink density varied as a
      function of developmental stage, with HP-to-dry mass ratio correlating highly to
      elastic modulus, even when enzymatic crosslink formation was inhibited.
      Multiphoton optical imaging corroborated LC-MS/MS data, identifying significant
      reductions in crosslink density from LOX inhibition. Taken together, crosslink
      density may be useful as a marker of tissue mechanical properties that could be
      assessed with imaging non-destructively and perhaps non-invasively. These
      outcomes could have significant scientific and clinical implications, enabling
      continuous and long-term monitoring of mechanical properties of collagen
      crosslinked tissues or engineered constructs. 

PMID- 24316365
TI  - Selective albumin-binding surfaces modified with a thrombin-inhibiting peptide.
AB  - Blood-contacting medical devices have been associated with severe clinical
      complications, such as thrombus formation, triggered by the activation of the
      coagulation cascade due to the adsorption of certain plasma proteins on the
      surface of biomaterials. Hence, the coating of such surfaces with antithrombotic
      agents has been used to increase biomaterial haemocompatibility. Biomaterial
      induced clotting may also be decreased by albumin adsorption from blood plasma in
      a selective and reversible way, since this protein is not involved in the
      coagulation cascade. In this context, this paper reports that the immobilization
      of the thrombin inhibitor D-Phe-Pro-D-Arg-D-Thr-CONH2 (fPrt) onto nanostructured
      surfaces induces selective and reversible adsorption of albumin, delaying the
      clotting time when compared to peptide-free surfaces. fPrt, synthesized with two
      glycine residues attached to the N-terminus (GGfPrt), was covalently immobilized
      onto self-assembled monolayers (SAMs) having different ratios of carboxylate
      hexa(ethylene glycol)- and tri(ethylene glycol)-terminated thiols (EG6-COOH/EG3)
      that were specifically designed to control GGfPrt orientation, exposure and
      density at the molecular level. In solution, GGfPrt was able to inactivate the
      enzymatic activity of thrombin and to delay plasma clotting time in a
      concentration-dependent way. After surface immobilization, and independently of
      its concentration, GGfPrt lost its selectivity to thrombin and its capacity to
      inhibit thrombin enzymatic activity against the chromogenic substrate n-p-tosyl
      Gly-Pro-Arg-p-nitroanilide. Nevertheless, surfaces with low concentrations of
      GGfPrt could delay the capacity of adsorbed thrombin to cleave fibrinogen. In
      contrast, GGfPrt immobilized in high concentrations was found to induce the
      procoagulant activity of the adsorbed thrombin. However, all surfaces containing
      GGfPrt have a plasma clotting time similar to the negative control (empty
      polystyrene wells), showing resistance to coagulation, which is explained by its
      capacity to adsorb albumin in a selective and reversible way. This work opens new
      perspectives to the improvement of the haemocompatibility of blood-contacting
      medical devices. 

PMID- 24316366
TI  - Structure-property effects of novel bioresorbable hybrid structures with
      controlled release of analgesic drugs for wound healing applications.
AB  - Over the last decades, wound dressings have developed from the traditional gauze
      dressing to tissue-engineered scaffolds. A wound dressing should ideally maintain
      a moist environment at the wound surface, allow gas exchange, act as a barrier to
      micro-organisms and remove excess exudates. In order to provide these
      characteristics, we developed and studied bioresorbable hybrid structures which
      combine a synthetic porous drug-loaded top layer with a spongy collagen sublayer.
      The top layer, prepared using the freeze-drying of inverted emulsions technique,
      was loaded with the analgesic drugs ibuprofen or bupivacaine, for controlled
      release to the wound site. Our investigation focused on the effects of the
      emulsion's parameters on the microstructure and on the resulting drug-release
      profile, as well as on the physical and mechanical properties. The structure of
      the semi-occlusive top layer enables control over vapor transmission, in addition
      to strongly affecting the drug release profile. Release of the analgesic drugs
      lasted from several days to more than 100 days. Higher organic:aqueous phase
      ratios and polymer contents reduced the burst release of both drugs and prolonged
      their release due to a lower porosity. The addition of reinforcing fibers to this
      layer improved the mechanical properties. Good binding of the two components,
      PDLGA and collagen, was achieved due to our special method of preparation, which
      enables a third interfacial layer in which both materials are mixed to create an
      "interphase". These new PDLGA/collagen structures demonstrated a promising
      potential for use in various wound healing applications.

PMID- 24316364
TI  - DNA-polymer conjugates for immune stimulation through Toll-like receptor 9
      mediated pathways.
AB  - Oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotide motifs are
      agonists of Toll-like receptor 9 and are currently being investigated for use as
      vaccine adjuvants through the promotion of type I immunity. Several classes of
      ODN have been developed which differ in their propensity to aggregate, which in
      turn alters cytokine profiles and cellular subsets activated. Although
      aggregation state is correlated with the change in cytokine response, it is
      unknown if this results from a change in the number of ODNs available for binding
      and/or the possible engagement of multiple TLR9 molecules. Here, we examined the
      role of ligand valency on the activation of TLR9 through the synthesis of ODN
      poly(acrylic acid) (PAA) conjugates. The compositions and size of the conjugates
      were characterized by UV-vis spectroscopy, proton nuclear magnetic resonance, gel
      permeation chromatography and dynamic light scattering. Enzyme-linked
      immunosorbent assays of cytokine secretion by murine-like macrophages indicate
      that these ODN-PAA polymer conjugates show enhanced immunostimulation at 100-fold
      lower concentrations than those required for ODN alone, for both TNF-alpha and IL
      6 release, and are more potent than any other previously reported multivalent ODN
      constructs. Increasing valency was shown to significantly enhance cytokine
      expression, particularly for IL-6. Knockdown by siRNA demonstrates that these
      polymer conjugates are specific to TLR9. Our results define valency as a critical
      design parameter and polymer conjugation as an advantageous strategy for
      producing ODN immunomodulatory agents. 

PMID- 24316367
TI  - Filling-in void and sparse regions in protein sequence space by protein-like
      artificial sequences enables remarkable enhancement in remote homology detection
      capability.
AB  - Protein functional annotation relies on the identification of accurate
      relationships, sequence divergence being a key factor. This is especially evident
      when distant protein relationships are demonstrated only with three-dimensional
      structures. To address this challenge, we describe a computational approach to
      purposefully bridge gaps between related protein families through directed design
      of protein-like "linker" sequences. For this, we represented SCOP domain
      families, integrated with sequence homologues, as multiple profiles and performed
      HMM-HMM alignments between related domain families. Where convincing alignments
      were achieved, we applied a roulette wheel-based method to design 3,611,010
      protein-like sequences corresponding to 374 SCOP folds. To analyze their ability
      to link proteins in homology searches, we used 3024 queries to search two
      databases, one containing only natural sequences and another one additionally
      containing designed sequences. Our results showed that augmented database
      searches showed up to 30% improvement in fold coverage for over 74% of the folds,
      with 52 folds achieving all theoretically possible connections. Although
      sequences could not be designed between some families, the availability of
      designed sequences between other families within the fold established the
      sequence continuum to demonstrate 373 difficult relationships. Ultimately, as a
      practical and realistic extension, we demonstrate that such protein-like
      sequences can be "plugged-into" routine and generic sequence database searches to
      empower not only remote homology detection but also fold recognition. Our richly
      statistically supported findings show that complementary searches in both
      databases will increase the effectiveness of sequence-based searches in
      recognizing all homologues sharing a common fold. 

PMID- 24316369
TI  - Trapeziometacarpal osteoarthrosis: clinical results and sonographic evaluation of
      the interposed tissue after trapeziectomy and first metacarpal suspension by
      external minifixation at a minimal two-year follow-up.
AB  - Among the surgical options to treat trapeziometacarpal osteoarthrosis,
      trapeziectomy has been criticized as unable to prevent postoperative collapse of
      the thumb, causing painful scapho-metacarpal impingement. The implantation of an
      external minifixator between the first and the second metacarpals for sufficient
      time has been proposed to maintain the postoperative space created by the bone
      resection to allow the development of a resistant interposed fibrous tissue.
      Nineteen patients (16 women, 3 men, mean age 64.5 years) were evaluated at 3.3
      years of follow-up after an unilateral trapeziectomy and first metacarpal
      suspension by external minifixation. Eighty-four percent of the patients were
      very satisfied with the operation. The mean DASH score was 27.7%, the pain 1.7/10
      (Visual Analogue Scale), the opening angle of the first web 58.3 degrees  and the
      Kapandji opposition score 9.5/10. Sonography demonstrated the existence of a
      strong fibrotic interposed tissue, preventing scapho-metacarpal impingement. The
      mean height of the trapeziectomy space (8.4mm) was maintained upon active pinch
      and maximal traction on the thumb. A significant atrophy of thenar muscles was
      also demonstrated, except for the Abductor pollicis brevis. In conclusion, total
      trapeziectomy with external minifixation provides acceptable clinical results,
      stabilizes the base of the thumb and prevents scapho-metacarpal impingement. The
      study brings also important new information about the nature of the interposed
      tissue in the trapezial space and about the state of the thenar muscles after
      trapeziectomy. 

PMID- 24316370
TI  - Inborn defects in the antioxidant systems of human red blood cells.
AB  - Red blood cells (RBCs) contain large amounts of iron and operate in highly
      oxygenated tissues. As a result, these cells encounter a continuous oxidative
      stress. Protective mechanisms against oxidation include prevention of formation
      of reactive oxygen species (ROS), scavenging of various forms of ROS, and repair
      of oxidized cellular contents. In general, a partial defect in any of these
      systems can harm RBCs and promote senescence, but is without chronic hemolytic
      complaints. In this review we summarize the often rare inborn defects that
      interfere with the various protective mechanisms present in RBCs. NADPH is the
      main source of reduction equivalents in RBCs, used by most of the protective
      systems. When NADPH becomes limiting, red cells are prone to being damaged. In
      many of the severe RBC enzyme deficiencies, a lack of protective enzyme activity
      is frustrating erythropoiesis or is not restricted to RBCs. Common hereditary RBC
      disorders, such as thalassemia, sickle-cell trait, and unstable hemoglobins, give
      rise to increased oxidative stress caused by free heme and iron generated from
      hemoglobin. The beneficial effect of thalassemia minor, sickle-cell trait, and
      glucose-6-phosphate dehydrogenase deficiency on survival of malaria infection may
      well be due to the shared feature of enhanced oxidative stress. This may inhibit
      parasite growth, enhance uptake of infected RBCs by spleen macrophages, and/or
      cause less cytoadherence of the infected cells to capillary endothelium. 

PMID- 24316368
TI  - Interrelationship between cytoplasmic retroviral Gag concentration and Gag
      membrane association.
AB  - The early events in the retrovirus assembly pathway, particularly the timing and
      nature of Gag translocation from the site of protein translation to the inner
      leaflet of the plasma membrane, are poorly understood. We have investigated the
      interrelationship between cytoplasmic Gag concentration and plasma membrane
      association using complementary live-cell biophysical fluorescence techniques in
      real time with both human T-cell leukemia virus type 1 (HTLV-1) and human
      immunodeficiency virus type 1 (HIV-1) Gag proteins. In particular, dual-color, z
      scan fluorescence fluctuation spectroscopy in conjunction with total internal
      reflection fluorescence and conventional, epi-illumination imaging were utilized.
      Our results demonstrate that HTLV-1 Gag is capable of membrane targeting and
      particle assembly at low (i.e., nanomolar) cytoplasmic concentrations and that
      there is a critical threshold concentration (approaching micromolar) prior to the
      observation of HIV-1 Gag associated with the plasma membrane. These observations
      imply fundamental differences between HIV-1 and HTLV-1 Gag trafficking and
      membrane association. 

PMID- 24316371
TI  - Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates
      mitochondrial abnormalities in obese mice.
AB  - A Mediterranean diet rich in olive oil has profound influence on health outcomes
      including metabolic syndrome. However, the active compound and detailed
      mechanisms still remain unclear. Hydroxytyrosol (HT), a major polyphenolic
      compound in virgin olive oil, has received increased attention for its
      antioxidative activity and regulation of mitochondrial function. Here, we
      investigated whether HT is the active compound in olive oil exerting a protective
      effect against metabolic syndrome. In this study, we show that HT could prevent
      high-fat-diet (HFD)-induced obesity, hyperglycemia, hyperlipidemia, and insulin
      resistance in C57BL/6J mice after 17 weeks supplementation. Within liver and
      skeletal muscle tissues, HT could decrease HFD-induced lipid deposits through
      inhibition of the SREBP-1c/FAS pathway, ameliorate HFD-induced oxidative stress
      by enhancing antioxidant enzyme activities, normalize expression of mitochondrial
      complex subunits and mitochondrial fission marker Drp1, and eventually inhibit
      apoptosis activation. Moreover, in muscle tissue, the levels of mitochondrial
      carbonyl protein were decreased and mitochondrial complex activities were
      significantly improved by HT supplementation. In db/db mice, HT significantly
      decreased fasting glucose, similar to metformin. Notably, HT decreased serum
      lipid, at which metformin failed. Also, HT was more effective at decreasing the
      oxidation levels of lipids and proteins in both liver and muscle tissue. Similar
      to the results in the HFD model, HT decreased muscle mitochondrial carbonyl
      protein levels and improved mitochondrial complex activities in db/db mice. Our
      study links the olive oil component HT to diabetes and metabolic disease through
      changes that are not limited to decreases in oxidative stress, suggesting a
      potential pharmaceutical or clinical use of HT in metabolic syndrome treatment. 

PMID- 24316372
TI  - Changes in the plastic properties of hippocampal dendritic spines underlie the
      attenuation of place learning in healthy aged rats.
AB  - Normal aging is characterized by slight impairments in spatial memory, and the
      modification of some electrophysiological parameters that underlie place learning
      and associated reference memory. However, the morphological mechanisms underlying
      these impairments remain unknown. In the present study, we analyzed the spine
      density and the proportion of thin, mushroom, stubby, wide, branched and double
      spines on pyramidal neuron dendrites in the hippocampal CA1 field of young and
      aged rats. These parameters were assessed both before and after evaluating place
      learning and reference memory in the Morris water maze. Aged rats adopted an
      egocentric strategy to resolve the task, swimming slower and further, and taking
      longer to locate the sunken platform. While probe trials revealed that aged
      animals could recall the platform position, these animals spent more time
      exploring incorrect quadrants than young rats. An increase in spine density was
      observed after task performance in both young and aged rats, but aging provoked a
      decrease in the density of thin spines. In addition, there was an increase in the
      density of mushroom and wide spines in aged animals after task performance as
      compared with the untested aged counterparts. Moreover, in aged animals there
      were fewer thin spines and more wide spines after task performance than in the
      young tested animals. These findings support the view that aging attenuates but
      does not abolish spatial memory, a process that may be associated with plastic
      changes in the type of dendritic spines on aged hippocampal CA1 neurons. 

PMID- 24316374
TI  - Deep sub micrometer imaging of defects in copper pillars by X-ray tomography in a
      SEM.
AB  - The potential of X-ray nanotomography hosted in a SEM in presented in this paper.
      In order to improve the detail detectability of this system, which is directly
      related to the X-ray source size, thin metal layers have been studied and
      installed in the equipment. A 3D resolution pattern has been created in order to
      determine the smallest detectable features by this setup. This sample is a 25 MUm
      diameter copper pillar in which size-controlled holes have been milled using a
      plasma-focused ion beam. This pattern has then been scanned and the resulting 3D
      reconstruction demonstrates that the instrument is able to detect 500 nm diameter
      voids in a copper interconnection, as used in 3D integration.

PMID- 24316373
TI  - Glycation cross-linking induced mechanical-enzymatic cleavage of microscale
      tendon fibers.
AB  - Recent molecular modeling data using collagen peptides predicted that mechanical
      force transmitted through intermolecular cross-links resulted in collagen triple
      helix unwinding. These simulations further predicted that this unwinding,
      referred to as triple helical microunfolding, occurred at forces well below
      canonical collagen damage mechanisms. Based in large part on these data, we
      hypothesized that mechanical loading of glycation cross-linked tendon microfibers
      would result in accelerated collagenolytic enzyme damage. This hypothesis is in
      stark contrast to reports in literature that indicated that individually
      mechanical loading or cross-linking each retards enzymatic degradation of
      collagen substrates. Using our Collagen Enzyme Mechano-Kinetic Automated Testing
      (CEMKAT) System we mechanically loaded collagen-rich tendon microfibers that had
      been chemically cross-linked with sugar and tested for degrading enzyme
      susceptibility. Our results indicated that cross-linked fibers were >5 times more
      resistant to enzymatic degradation while unloaded but became highly susceptible
      to enzyme cleavage when they were stretched by an applied mechanical deformation.

PMID- 24316375
TI  - Evaluation of (arene)Ru(II) complexes of curcumin as inhibitors of dipeptidyl
      peptidase IV.
AB  - Curcumin, the main component of Curcuma longa, shows an anti-hyperglycemic effect
      and improved insulin sensitivity. This action may be attributed at least in part
      to its anti-inflammatory properties and also to its possible interaction with
      dipeptidyl peptidase-4 (DPPIV), the enzyme that the conversion of glucagon-like
      peptide-1 (GLP-1), responsible for glucose tolerance into inactive GLP-1. In this
      work we evaluated the inhibitory activities of a series of different arene-Ru(II)
      curcumin complexes on bovine kidney dipeptidyl peptidase-4 (DPPIV). We studied
      also the interaction of these inhibitors on the enzyme with fluorescence studies
      displaying the binding poses with molecular docking studies. Specifically
      organometallic ruthenium(II) complexes of general formula [(eta(6)
      arene)Ru(curcuminato)Cl], with arene being p-(i)PrC6H4Me (1), C6H6 (2), and C6Me6
      (3), were evaluated for their inhibition activity toward the mammalian enzyme.
      Among them, 2 suppressed DPPIV activities more potently (Ki = 20.2(+/-0.8) MUM)
      than 1, 3, or free curcumin, and all complexes showed an antioxidant activity as
      free curcumin. As shown from our docking simulations a putative binding site of
      the compound 2 was found on subdomains S1 and S2 of DPP-IV, where S1 hydrophobic
      pocket includes catalytic residues and is the primary determinant of substrate
      specificity for the enzyme. Collectively, our results demonstrate that the
      complexation of curcumin with ruthenium(II) could be a promising starting point
      for the development of curcumin-based DPPIV inhibitors. 

PMID- 24316377
TI  - Elevated expression of Piwi and piRNAs in ovaries of triploid crucian carp.
AB  - Increasing piRNAs provide RNA-interference pathways to regulate transposons and
      gene expression in germline cells. We demonstrate that Piwi transcripts are
      exclusively expressed in adult testes and ovaries in teleosts, with triploids
      showing the highest Piwi expression in the ovaries. Studies in vivo and in vitro
      showed that hCG and E2 treatment suppressed Piwi expression. We further cloned
      200 small RNAs in the three kinds of fish. Seven piRNAs were obtained from all
      the three different ploidy fishes. During ovulation, five piRNAs showed
      significantly higher expression in the ovaries of sterile triploids than fertile
      diploids and tetraploids. Furthermore, E2 suppressed the expression of the six
      piRNAs at different levels in vivo and in vitro. The present study bridges the
      gap between the HPG axis and Piwi-piRNA pathway by suggesting that a
      dysfunctional HPG axis abrogated the piRNA suppression in triploid fish. 

PMID- 24316376
TI  - Differential expression of nasal embryonic LHRH factor (NELF) variants in
      immortalized GnRH neuronal cell lines.
AB  - NELF, a protein identified in migratory GnRH neurons, is predominantly nuclear
      and alternatively spliced. However, specific NELF splice variants expressed in
      immortalized GnRH neuronal cell lines from mouse and human are not known. RNA
      from migratory (GN11 and NLT) and postmigratory (GT1-7) cells in mouse, and
      (FNCB4-hTERT) cells in human was subjected to RT-PCR. RT-PCR products were
      cloned, electrophoresed on denaturing gradient gels and sequenced. In addition,
      quantitative RT-PCR was performed using variant-specific primers. Western blot
      and immunofluorescence using confocal microscopy were performed for selected
      variants. Nelf variant 2 (v2), which contains a nuclear localization signal
      (NLS), was the predominant variant in all mouse and human GnRH neurons. Variants
      without a NLS (v3 in mouse; v4 in human) were identified. In mouse, v2 protein
      expression was nuclear, while v3 was non-nuclear. In mouse GnRH neurons, six Nelf
      splice variant transcripts were identified, including three previously unreported
      variants. In human, four NELF variant transcripts were observed. In both mouse
      and human, nuclear and non-nuclear variant transcript and protein were
      identified, explaining variable NELF cellular localization. 

PMID- 24316378
TI  - Quercetin supplementation restores testicular function and augments germ cell
      survival in the estrogenized rats.
AB  - Quercetin, as a flavonoid, has been recognized to possess dual properties of an
      oxidant and antioxidant as well. The role of quercetin (QC), as an antioxidant in
      countering estradiol-3-benzoate (EB) induced adverse effects and germ cell
      apoptosis in adult rat testis was presently investigated. Adult rats received EB
      (0.075 mg/rat/5th day) alone or EB+QC (15 mg/kg bw/alternate day) simultaneously
      for 30 days. Revival of spermatogenesis following QC intervention was associated
      with a significant restoration in serum and intra-testicular levels of
      testosterone. Decline in lipid peroxidation and simultaneous improvement in the
      activities of superoxide dismutase, catalase and glutathione s-transferase were
      very much evident. Identically, total antioxidant capacity and glutathione
      demonstrated a marked improvement. QC augmented germ cell survival leading to a
      decrease in cell apoptosis. Expression of downstream apoptotic markers, caspase-3
      and poly-ADP-ribose polymerase (PARP) presented a significant reduction. Down
      regulation with respect to upstream markers, caspase-8 and -9, Fas, FasL, Bax,
      and p53 was similarly observed. Taken together, the above findings indicate that
      with the dose presently used quercetin with its antioxidant and antiestrogenic
      properties restored testicular function leading to revival of spermatogenesis. It
      also augmented germ cell survival primarily mediated through downregulation in
      the expressions of upstream, downstream and other markers in the pathways of
      metazoan apoptosis.

PMID- 24316380
TI  - The chloroplast genome of a Symbiodinium sp. clade C3 isolate.
AB  - Dinoflagellate algae of the genus Symbiodinium form important symbioses within
      corals and other benthic marine animals. Dinoflagellates possess an extremely
      reduced plastid genome relative to those examined in plants and other algae. In
      dinoflagellates the plastid genes are located on small plasmids, commonly
      referred to as 'minicircles'. However, the chloroplast genomes of dinoflagellates
      have only been extensively characterised from a handful of species. There is also
      evidence of considerable variation in the chloroplast genome organisation across
      those species that have been examined. We therefore characterised the chloroplast
      genome from an environmental coral isolate, in this case containing a symbiont
      belonging to the Symbiodinium sp. clade C3. The gene content of the genome is
      well conserved with respect to previously characterised genomes. However, unlike
      previously characterised dinoflagellate chloroplast genomes we did not identify
      any 'empty' minicircles. The sequences of this chloroplast genome show a high
      rate of evolution relative to other algal species. Particularly notable was a
      surprisingly high level of sequence divergence within the core polypeptides of
      photosystem I, the reasons for which are currently unknown. This chloroplast
      genome also possesses distinctive codon usage and GC content. These features
      suggest that chloroplast genomes in Symbiodinium are highly plastic. 

PMID- 24316379
TI  - Functional assessment of the mutational effects of human IRAK4 and MyD88 genes.
AB  - Human interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency and myeloid
      differentiating factor 88 (MyD88) deficiency syndromes are two primary immune
      deficiency disorders with innate immune defects. Although new genetic variations
      of IRAK4 and MyD88 have recently been deposited in the single nucleotide
      polymorphism (SNP) database, the clinical significance of these variants has not
      yet been established. Therefore, it is important to establish methods for
      assessing the association of each gene variation with human diseases. Because
      cell-based assays, western blotting and an NF-kappaB reporter gene assay, showed
      no difference in protein expression and NF-kappaB activity between R12C and wild
      type IRAK4, we examined protein-protein interactions of purified recombinant
      IRAK4 and MyD88 proteins by analytical gel filtration and NMR titration. We found
      that the variant of IRAK4, R12C, as well as R20W, located in the death domain of
      IRAK4 and regarded as a SNP, caused a loss of interaction with MyD88. Our studies
      suggest that not only the loss of protein expression but also the defect of
      Myddosome formation could cause IRAK4 and MyD88 deficiency syndromes. Moreover a
      combination of in vitro functional assays is effective for confirming the
      pathogenicity of mutants found in IRAK4 and MyD88-deficiency patients. 

PMID- 24316381
TI  - Training of transversus abdominis activation in the supine position with
      ultrasound biofeedback translated to increased transversus abdominis activation
      during upright loaded functional tasks.
AB  - OBJECTIVE: To determine whether healthy adults successfully completing
      transversus abdominis (TrA) muscle activation training in the supine position
      with clinician and ultrasound (US) imaging feedback increase their TrA activation
      during lifting and reaching tasks performed in the standing position. DESIGN:
      Prospective longitudinal within-subject, repeated-measures (RM) study. SETTING:
      University laboratory. PARTICIPANTS: A total of 19 of 24 asymptomatic adult
      volunteers met inclusion criteria. METHODS: Each adult performed 3 trials of 5
      functional tasks before receiving any training. They were then briefed on the
      abdominal draw-in maneuver via educational materials. Next, each adult received
      individualized TrA activation training while in the supine position with
      clinician and US feedback of TrA activation. At 5 minutes after TrA activation
      training, each adult who met the criterion during training performed 3 trials of
      these same 5 functional tasks. Tasks were randomized during these test sessions.
      Adults who returned 5 months later (n = 10) were tested again on 3 trials of 3 of
      these tasks. No feedback was provided during test sessions. Recorded cine loop
      images were obtained via US per trial and masked for TrA measurement. MAIN
      OUTCOME MEASUREMENTS: Resting state (minimum thickness) and contraction state
      (maximum thickness) of TrA were measured per recorded trial by a clinician who
      was shown to have high reliability. The percentage of change in TrA thickness
      {[(thicknessmax - thicknessmin)/ thicknessmin] * (100)} was the primary outcome
      measure. Trial averages were formed per measure per task per test session per
      adult. RESULTS: A 2-test sessions (pretraining, 5-minutes post-training) * 5
      tasks RM analysis of variance (N = 19) indicated a significant and large effect
      for test sessions (P < .001, eta(2) = 0.808) and moderate effect for tasks (P =
      .011; eta(2) = 0.164). Likewise, a 3-test sessions (pretraining, 5-minutes
      posttraining, 5 months post-training) * 3 tasks RM analysis of variance (n = 10)
      indicated a significant and large test sessions effect (P < .001, eta(2) = 0.57)
      and no task effect. Overall, the percent change in TrA thickness increased after
      the TrA activation training program and was maintained at 5 months; similar
      patterns of improvement were noted across test sessions and tasks. CONCLUSION:
      Asymptomatic adults successfully completing a short session of TrA activation
      training in the supine position with US feedback of TrA activation were able to
      increase their TrA activation during loaded lifting and reaching tasks for at
      least 5 months.

PMID- 24316382
TI  - Estrogen-mediated activation of fibroblasts and its effects on the fibroid cell
      proliferation.
AB  - In this study, we explored the role of estrogen-mediated activation of stromal
      fibroblasts in the pathogenesis of uterine fibroid in patients. We isolated
      uterine fibroids and surrounding smooth muscle from patients and separated
      fibroblasts using immunomagnetic beads. We also measured the expression levels of
      estrogen receptors in fibroblasts and examined cell proliferation, expressions of
      fibroblast activation protein (FAP), extracellular matrix (ECM) (fibronectin,
      laminin, collagen I), growth factors (transforming growth factor-beta, insulin
      like growth factor-1), and cell proliferation pathway stimulated by estrogen. We
      also silenced the expression of FAP by RNA interference and analyzed the
      expression levels of these markers before and after E2 stimulation. Finally, we
      also investigated the effect of activated fibroblast supernatant on cell
      proliferation of fibroblasts, smooth muscle cells, and fibroid cells. We found
      that fibroblasts in uterine fibroid were activated, and the expression levels of
      estrogen receptors from fibroid cells were higher than those from smooth muscle
      cells. After estrogen stimulation, the proliferation activity of fibroblast was
      enhanced, and the expression of FAP, ECM, and growth factors was increased; the
      signaling pathway involved in cell proliferation was also activated.
      Interestingly, the activated fibroblast supernatant stimulation can promote cell
      proliferation. Silencing of FAP expression could inhibit the E2-mediated
      biological effects. In conclusion, estrogen promotes proliferation of uterine
      fibroids through the activation of fibroblasts, thus, activated fibroblasts may
      play an important role in the pathogenesis of uterine fibroids, which could be
      targeted in future for the treatment of uterine fibroid. 

PMID- 24316384
TI  - Competition in di- and tri-trophic food web modules.
AB  - Competition in di- and tri-trophic food web modules with many competing species
      is studied. The food web modules considered are apparent competition between n
      species sharing a single predator and a diamond-like food web with a single
      resource, a single top predator and many competing middle species. The predators
      have either fixed preferences for their prey, or they switch between available
      prey in a way that maximizes their fitness. Dependence of these food web dynamics
      on environmental carrying capacity and food web connectance is studied. The
      results predict that optimal flexible foraging strongly weakens apparent
      competition and promotes species coexistence. Food web robustness (defined here
      as the proportion of surviving species) does not decrease with increased
      connectance in these food-webs. Moreover, it is shown that flexible prey
      switching leads to the same population equilibria as in corresponding food webs
      with highly specialized predators. The results show that flexible foraging
      behavior by predators can have very strong impact on species richness, as well as
      the response of communities to changes in resource enrichment and food-web
      connectance when compared to the same food-web topology with inflexible top
      predators. Several results on global stability using Lyapunov functions are
      provided. 

PMID- 24316385
TI  - COStar: a D-star Lite-based dynamic search algorithm for codon optimization.
AB  - Codon optimized genes have two major advantages: they simplify de novo gene
      synthesis and increase the expression level in target hosts. Often they achieve
      this by altering codon usage in a given gene. Codon optimization is complex
      because it usually needs to achieve multiple opposing goals. In practice, finding
      an optimal sequence from the massive number of possible combinations of
      synonymous codons that can code for the same amino acid sequence is a challenging
      task. In this article, we introduce COStar, a D-star Lite-based dynamic search
      algorithm for codon optimization. The algorithm first maps the codon optimization
      problem into a weighted directed acyclic graph using a sliding window approach.
      Then, the D-star Lite algorithm is used to compute the shortest path from the
      start site to the target site in the resulting graph. Optimizing a gene is thus
      converted to a search in real-time for a shortest path in a generated graph.
      Using in silico experiments, the performance of the algorithm was shown by
      optimizing the different genes including the human genome. The results suggest
      that COStar is a promising codon optimization tool for de novo gene synthesis and
      heterologous gene expression. 

PMID- 24316383
TI  - Drugs that modulate aging: the promising yet difficult path ahead.
AB  - Once a backwater in medical sciences, aging research has emerged and now
      threatens to take the forefront. This dramatic change of stature is driven from 3
      major events. First and foremost, the world is rapidly getting old. Never before
      have we lived in a demographic environment like today, and the trends will
      continue such that 20% percent of the global population of 9 billion will be over
      the age of 60 by 2050. Given current trends of sharply increasing chronic disease
      incidence, economic disaster from the impending silver tsunami may be ahead. A
      second major driver on the rise is the dramatic progress that aging research has
      made using invertebrate models such as worms, flies, and yeast. Genetic
      approaches using these organisms have led to hundreds of aging genes and, perhaps
      surprisingly, strong evidence of evolutionary conservation among longevity
      pathways between disparate species, including mammals. Current studies suggest
      that this conservation may extend to humans. Finally, small molecules such as
      rapamycin and resveratrol have been identified that slow aging in model
      organisms, although only rapamycin to date impacts longevity in mice. The
      potential now exists to delay human aging, whether it is through known classes of
      small molecules or a plethora of emerging ones. But how can a drug that slows
      aging become approved and make it to market when aging is not defined as a
      disease. Here, we discuss the strategies to translate discoveries from aging
      research into drugs. Will aging research lead to novel therapies toward chronic
      disease, prevention of disease or be targeted directly at extending lifespan? 

PMID- 24316386
TI  - No senescence despite declining selection pressure: Hamilton's result in broader
      perspective.
AB  - Theory predicts that senescence should inevitably evolve because selection
      pressure declines with age. Yet, data show that senescence is not a universal
      phenomenon. How can these observations peacefully coexist? Evolution of any trait
      hinges on its impact on fitness. A complete mathematical description of change in
      fitness, the total fitness differential, involves selection pressure along with a
      perturbation function that describes how the vital rates, mortality and
      fecundity, are affected across ages. We propose that the perturbation function
      can be used to model trade-offs when vital rates are perturbed in different
      directions and magnitude at different ages. We find that for every trade-off we
      can identify parameter values for which senescence does evolve and others for
      which it does not. We argue that this reconciles the apparent contradiction
      between data and theory. The total fitness differential is also instrumental in
      deriving mathematical relationships between alternative indicators of selection
      pressure. We show examples and highlight that any indicator combined with the
      right perturbation function can be used to parameterize a specific biological
      change. Biological considerations should motivate what perturbation functions are
      used. We interpret the relevance of Hamilton's finding that selection pressure
      declines for the evolution of senescence: declining selection pressure is a
      necessary but not a sufficient condition. 

PMID- 24316387
TI  - A two-stage SVM method to predict membrane protein types by incorporating amino
      acid classifications and physicochemical properties into a general form of Chou's
      PseAAC.
AB  - Membrane proteins play important roles in many biochemical processes and are also
      attractive targets of drug discovery for various diseases. The elucidation of
      membrane protein types provides clues for understanding the structure and
      function of proteins. Recently we developed a novel system for predicting protein
      subnuclear localizations. In this paper, we propose a simplified version of our
      system for predicting membrane protein types directly from primary protein
      structures, which incorporates amino acid classifications and physicochemical
      properties into a general form of pseudo-amino acid composition. In this
      simplified system, we will design a two-stage multi-class support vector machine
      combined with a two-step optimal feature selection process, which proves very
      effective in our experiments. The performance of the present method is evaluated
      on two benchmark datasets consisting of five types of membrane proteins. The
      overall accuracies of prediction for five types are 93.25% and 96.61% via the
      jackknife test and independent dataset test, respectively. These results indicate
      that our method is effective and valuable for predicting membrane protein types.
      A web server for the proposed method is available at
      http://www.juemengt.com/jcc/memty_page.php. 

PMID- 24316388
TI  - Neuroprotective effects of recombinant human granulocyte colony-stimulating
      factor (G-CSF) in a rat model of anterior ischemic optic neuropathy (rAION).
AB  - The purpose of this study was to investigate the neuroprotective effects of
      recombinant human granulocyte colony stimulating factor (G-CSF), as administered
      in a rat model of anterior ischemic optic neuropathy (rAION). Using laser-induced
      photoactivation of intravenously administered Rose Bengal in the optic nerve head
      of 60 adult male Wistar rats, an anterior ischemic optic neuropathy (rAION) was
      inducted. Rats either immediately received G-CSF (subcutaneous injections) or
      phosphate buffered saline (PBS) for 5 consecutive days. Rats were euthanized at 4
      weeks post infarct. Density of retinal ganglion cells (RGCs) was counted using
      retrograde labeling of Fluoro-gold. Visual function was assessed by flash visual
      evoked potentials (FVEP) at 4 weeks. TUNEL assay in the retinal sections and
      immunohistochemical staining of ED1 (marker of macrophage/microglia) were
      investigated in the optic nerve (ON) specimens. The RGC densities in the central
      and mid-peripheral retinas in the G-CSF treated rats were significantly higher
      than those of the PBS-treated rats (survival rate was 71.4% vs. 33.2% in the
      central retina; 61.8% vs. 22.7% in the mid-peripheral retina, respectively; both
      p < 0.05). FVEP measurements showed a significantly better preserved latency and
      amplitude of the p1 wave in the G-CSF-treated rats than that of the PBS-treated
      rats (latency120 +/- 11 ms vs. 142 +/- 12 ms, p = 0.03; amplitude 50 +/- 11 MUv
      vs. 31 +/- 13 MUv, p = 0.04). TUNEL assays showed fewer apoptotic cells in the
      retinal ganglion cell layers of G-CSF treated rats [2.1 +/- 1.0 cells/high power
      field (HPF) vs. 8.0 +/- 1.5/HPF; p = 0.0001]. In addition, the number of ED1
      positive cells was attenuated at the optic nerve sections of G-CSF-treated rats
      (16 +/- 6/HPF vs. 35 +/- 10/HPF; p = 0.016). In conclusion, administration of G
      CSF is neuroprotective in the rat model of anterior ischemic optic neuropathy, as
      demonstrated both structurally by RGC density and functionally by FVEP. G-CSF may
      work via the dual actions of anti-apoptosis for RGC surviving as well as anti
      inflammation in the optic nerves as evidenced by less infiltration of ED1
      povitive cells. 

PMID- 24316390
TI  - Locum doctors: Patient safety is more important than the cost.

PMID- 24316389
TI  - Virtual reality case-specific rehearsal in temporal bone surgery: a preliminary
      evaluation.
AB  - OBJECTIVES: 1. To investigate the feasibility of performing case-specific
      surgical rehearsal using a virtual reality temporal bone simulator. 2. To
      identify potential clinical applications in temporal bone surgery. DESIGN:
      Prospective assessment study. SETTING: St Mary's Hospital, Imperial College NHS
      Trust, London UK. PARTICIPANTS: Sixteen participants consisting of a trainer and
      trainee group. METHOD: Twenty-four cadaver temporal bones were CT-scanned and
      uploaded onto the Voxelman simulator. Sixteen participants performed a 90-min
      temporal bone dissection on the generic simulation model followed by 3 dissection
      tasks on the case simulation and cadaver models. Case rehearsal was assessed for
      feasibility. Clinical applications and usefulness were evaluated using a 5-point
      Likert-type scale. RESULTS: The upload process required a semi-automated system.
      Average time for upload was 20 min. Suboptimal reconstruction occurred in 21% of
      cases arising when the mastoid process and ossicular chain were not captured (n =
      2) or when artefact was generated (n = 3). Case rehearsal rated highly (Likert
      score >4) for confidence (75%), facilitating planning (75%) and training (94%).
      Potential clinical applications for case rehearsal include ossicular chain
      surgery, cochlear implantation and congenital anomalies. Case rehearsal of
      cholesteatoma surgery is not possible on the current platform due to suboptimal
      soft tissue representation. CONCLUSION: The process of uploading CT data onto a
      virtual reality temporal bone simulator to perform surgical rehearsal is feasible
      using a semi-automated system. Further clinical evaluation is warranted to assess
      the benefit of performing patient-specific surgical rehearsal in selected
      procedures.

PMID- 24316391
TI  - Study to evaluate the role of severity stratification of skin and soft tissue
      infections (SSTIs) in formulating treatment strategies and predicting poor
      prognostic factors.
AB  - BACKGROUND: Diagnosis of skin and soft tissue infections (SSTIs) is difficult as
      they commonly masquerade as other clinical syndromes. So, the prospective cohort
      study was carried out to study the clinical profile, evaluate the existing method
      of severity stratification of SSTIs and identify factors responsible for
      prolonged stay and poor outcome in patients with SSTIs. METHODS: The prospective
      study was carried out based on clinical profile to evaluate the role of severity
      stratification of SSTIs in 105 patients attending the surgical outpatient
      department and surgical emergency. The patients were managed conservatively on
      oral or intravenous antibiotics and dressing or combined with surgical
      intervention based on severity stratification. Sometimes radiological
      investigation helped to know the deep seated abscess and thereby need of early
      intervention by surgical drainage, fasciotomy and rarely amputation. The data
      collected, summarised and evaluated using chi-square method. RESULT: SSTIs has
      been categorized into mild, moderate and severe form based on clinical and
      demographic profile of the patient. The study revealed risk factors that were
      statistically significant to be male patients of lower socioeconomic groups,
      temperature above 38  degrees C, hypotension, TLC > 15000, presence of gangrene,
      bullae, crepitus, trauma, animal/insect bite, BSA > 9% except when involving
      hand, head & scrotum, loss of sensation, loss of movement/function of affected
      part and restriction of joint movement (P < 0.05). CONCLUSION: Based on above
      findings, an algorithm for severity stratification is formulated for reducing the
      morbidity and mortality of the patients with SSTIs.

PMID- 24316392
TI  - A new PKCalpha/beta/TBX3/E-cadherin pathway is involved in PLCepsilon-regulated
      invasion and migration in human bladder cancer cells.
AB  - Although PLCepsilon has been verified to enhance bladder cancer cell invasion,
      the signaling pathways responsible for this remain elusive. Protein kinase C
      (PKCalpha/beta), which is involved in cancer development and progression, has
      been demonstrated to be activated by PLCepsilon. However, the roles of
      PKCalpha/beta in PLCepsilon-mediated bladder carcinoma cell invasion and
      migration have not been clearly identified. In this study, to determine what role
      PKCalpha/beta plays in PLCepsilon-mediated bladder cancer cell invasion and
      migration, we silenced PLCepsilon gene by adenovirus-shPLCepsilon in T24 and BIU
      87 cells and then revealed that it significantly inhibited cell migration and
      invasion. Further research indicated that cell bio-function of PLCepsilon
      regulated was related with PKCalpha/beta activity. These in vitro findings were
      supported by data from bladder carcinoma patient samples. In 35 case bladder
      cancer tumor samples, PLCepsilon-overexpressing tumors showed significantly
      higher positive rates of PKCalpha/beta membrane immunohistochemistry staining
      than PLCepsilon-low-expressing tumors. Mechanistically, study further showed that
      PLCepsilon knockdown gene induced E-cadherin expression and decreased TBX3
      expression, both of which were dependent on PKCalpha/beta activity. In addition,
      we demonstrated that treatment cells with TBX3-specific shorting hairpin RNA
      (shRNA) up-regulated E-cadherin expression and inhibited cell invasion/migration.
      Moreover, in in vivo experiment, immunohistochemistry analysis of Ad-shPLCepsilon
      infected tumor tissue showed low expression levels of phospho-PKCalpha/beta and
      TBX3 and high expression levels of E-cadherin compared with those of the control
      group. In summary, our findings uncover that PKCalpha/beta is critical for
      PLCepsilon-mediated cancer cell invasion and migration and provide valuable
      insights for current and future Ad-shPLCepsilon and PKCalpha/beta clinical
      trials. 

PMID- 24316393
TI  - Increased plasma high-sensitivity C-reactive protein and myeloperoxidase levels
      may predict ischemia during myocardial perfusion imaging in slow coronary flow.
AB  - BACKGROUND AND AIMS: It is unclear whether changes in plasma levels of
      inflammatory markers could explain the link between ischemia and slow coronary
      flow (SCF). The aim of the study was to evaluate the plasma levels of high
      sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and myeloperoxidase
      (MPO) during myocardial perfusion imaging (MPI) in SCF patients. METHODS: The
      study population consisted of 53 SCF patients and 30 controls. Coronary flow
      rates were documented by TIMI frame count (TFC). Plasma levels of hsCRP, IL-6,
      MPO, and MPI were obtained in all participants. RESULTS: hsCRP, IL-6 and MPO
      levels of SCF patients were higher than controls (hsCRP: 4.7 +/- 2.5 vs. 1.7 +/-
      1.1 mg/L, p <0.001; IL-6: 8.2 +/- 4.3 vs. 5.2 +/- 2.1 pg/mL, p <0.001; and MPO:
      75.9 +/- 59.6 vs. 24.3 +/- 16.7 ng/mL, p <0.001). Twenty-one SCF patients
      exhibited myocardial perfusion defect (MPD) on MPI. In SCF patients, the highest
      hsCRP, IL-6 and MPO levels were observed in patients with both MPD and three
      vessel slow flow. Mean TFCs were positively correlated with plasma levels of
      hsCRP (r = 0.424, p = 0.002), IL-6 (r = 0.367, p = 0.007), MPO (r = 0.430, p =
      0.001), and reversibility score (r = 0.671, p <0.001) in SCF patients. HsCRP and
      MPO were the independent variables, which predicted positive MPI results (hsCRP:
      OR, 2.176; 95% CI, 1.200-3.943; p = 0.010, MPO: OR, 1.026; 95% CI, 1.007-1.046; p
      = 0.008). CONCLUSIONS: Inflammation may play a crucial role in both the
      pathogenesis and development of ischemia in SCF. Association of increased levels
      of inflammatory markers and ischemia suggests that endothelial inflammation may
      be largely responsible for clinical presentation. New combined treatment regimens
      should target endothelial activation and inflammation in SCF.

PMID- 24316394
TI  - Uric acid levels in obstructive sleep apnea patients with atrial fibrillation.
AB  - BACKGROUND AND AIMS: The objective of this observational study was to determine
      whether there is an association between atrial fibrillation (AF) and uric acid
      and to identify the risk markers for AF in obstructive sleep apnea (OSA).
      METHODS: Consecutive patients with newly diagnosed OSA were screened at baseline.
      The final study population consisted of 516 patients. One hundred and eight
      patients had AF. Demographic, clinical, laboratory, and echocardiographic
      characteristics were carefully recorded. Logistic regression was used for the
      multivariate analysis of independent risk factors. RESULTS: Uric acid,
      triglyceride, high-density lipoprotein, C-reactive protein (CRP), left atrial
      diameter, interventricular septum thickness, apnea hypopnea index, and Epworth
      sleepiness scale were significantly higher in OSA patients with AF than in those
      without AF (p <0.05). Among these patients, multiple logistic analyses indicated
      the independent risk factors for AF occurrence in the OSA subjects included serum
      uric acid level, left atrial diameter, percentage of time with SaO2 <90%, CRP.
      The diagnosis analysis showed that higher uric acid, CRP, left atrial diameter
      and percentage of time with SaO2 <90% had a significant ability to reflect the
      presence of AF occurrence. CONCLUSIONS: The novel finding of this study is that
      the occurrence of AF in OSA patients is strongly related to serum uric acid
      level, left atrial diameter, percentage of time with SaO2 <90% and CRP level.
      These results may be helpful for monitoring AF occurrence in OSA patients.

PMID- 24316395
TI  - Common genetic variants in 53BP1 associated with nonsmall-cell lung cancer risk
      in Han Chinese.
AB  - BACKGROUND AND AIMS: The study investigated several common SNPs in the tumor
      protein p53 binding protein 1 gene and tumor protein p53 gene in 640 lung cancer
      cases and 685 controls in Han Chinese to determine if these single nucleotide
      polymorphisms (SNPs) were associated with lung cancer risk. Several studies
      indicated that SNPs in the 53BP1 and TP53 gene are associated with cancer risk.
      We investigated the association between common SNP variants in the 53BP1, TP53
      gene and lung cancer risk. METHODS: We used real-time PCR method to investigate
      the genotypic frequencies of rs2602141, rs560191 and rs689647 in 53BP1 and
      rs1042522 in TP53 in 640 cases of lung cancer and 685 controls. RESULTS: SNPs
      rs2602141, rs560191 and rs689647 in 53BP1 were in complete linkage disequilibrium
      in Han Chinese. The frequencies of the G/G, G/T and T/T genotypes of rs2602141
      were 17.5, 50.3 and 32.2% in cases and 21.0, 49.3 and 29.6% in controls,
      respectively and distributions were not significantly different (p = 0.236). The
      rs2602141 T/T genotype increased NSCLC risk (OR = 1.56, 95% CI = 1.10-2.21).
      CONCLUSIONS: The genotype distribution frequency of rs1042522 does not
      demonstrate significant differences between cases and control group. 53BP1 and
      TP53 gene interactions were not associated with lung cancer risk.

PMID- 24316396
TI  - Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression
      mechanism.
AB  - BACKGROUND AND AIMS: The MAGE gene encodes cancer/testis antigens that are
      selectively expressed in various types of human neoplasms but not in normal
      tissues other than testis and placenta. However, the expression pattern of MAGE
      A9 and MAGE-A11 in breast cancer patients is still unclear. The purpose of our
      study is to investigate the expression pattern and mechanism of MAGE-A9 and MAGE
      A11 in breast cancer patients. METHODS: The expression of MAGE-A9 and MAGE-A11
      was investigated in 60 breast benign diseases specimens, 60 tumor-free breast
      specimens and 60 breast cancer specimens by RT-PCR, and their correlation with
      clinicopathological parameters was elucidated. We examined the influence of the
      DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) together with the
      histone deacetylase inhibitor trichostatin A (TSA) on the expression of MAGE-A9
      and MAGE-A11 genes in two breast cancer cell lines. RESULTS: The expression rates
      of MAGE-A9 and MAGE-A11 in breast cancer specimens were 45 and 66.7%,
      respectively. MAGE-A9 and MAGE-A11 expression was positively associated with
      estrogen-receptor (ER) and HER-2 expression (p <0.05). 5-Aza-CdR treatment alone
      could induce the expression of MAGE-A9 and MAGE-A11 in cell lines that did not
      express this antigen. TSA treatment alone had no influence on MAGE-A9 and MAGE
      A11 gene expression. However, TSA was able synergistically to enhance 5-aza-CdR
      mediated MAGE-A transcription (p <0.05). CONCLUSIONS: Our data show that MAGE-A9
      and MAGE-A11 are tumor-specific antigens and not only DNA hypermethylation but
      also histone deacetylation is responsible for the mechanism underlying MAGE-A9
      and MAGE-A11 gene silencing.

PMID- 24316397
TI  - PU.1 promotes cell cycle exit in the murine myeloid lineage associated with
      downregulation of E2F1.
AB  - Acute myeloid leukemia (AML) is characterized by increased proliferation and
      reduced differentiation of myeloid lineage cells. AML is frequently associated
      with mutations or chromosomal rearrangements involving transcription factors.
      PU.1 (encoded by Sfpi1) is an E26 transformation-specific family transcription
      factor that is required for myeloid differentiation. Reduced PU.1 levels, caused
      by either mutation or repression, are associated with human AML and are
      sufficient to cause AML in mice. The objective of this study was to determine
      whether reduced PU.1 expression induces deregulation of the cell cycle in the
      myeloid lineage. Our results showed that immature myeloid cells expressing
      reduced PU.1 levels (Sfpi1(BN/BN) myeloid cells) proliferated indefinitely in
      cell culture and expanded in vivo. Transplantation of Sfpi1(BN/BN) cells induced
      AML in recipient mice. Cultured Sfpi1(BN/BN) cells expressed elevated messenger
      RNA transcript and protein levels of E2F1, an important regulator of cell cycle
      entry. Restoration of PU.1 expression in Sfpi1(BN/BN) myeloid cells blocked
      proliferation, induced differentiation, and reduced E2F1 expression. Taken
      together, these data show that PU.1 controls cell cycle exit in the myeloid
      lineage associated with downregulation of E2F1 expression. 

PMID- 24316398
TI  - Abnormal rectal endocrine cells in patients with irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. In a
      previous study the total number of endocrine cells in the rectum of IBS patients,
      as detected by chromogranin A, did not differ from that of healthy controls.
      While the total endocrine cell content of the rectum appears to be unchanged in
      IBS patients, changes in particular endocrine cells cannot be excluded. This
      study was undertaken, therefore, to investigate the cell density of different
      rectal endocrine cell types in (IBS) patients. Fifty patients with IBS (41
      females and 9 males) were included in the study. Thirty patients had diarrhoea
      (IBS-D) and 20 had constipation (IBS-C) as the predominant symptom. Twenty-seven
      subjects were included as controls (19 females and 8 males). Rectal biopsy
      specimens were immunostained using the avidin-biotin-complex method for
      serotonin, peptide YY (PYY), pancreatic polypeptide (PP), and oxyntomodulin and
      somatostatin cells. The cell densities were quantified by computerised image
      analysis. The serotonin cell density did not differ significantly, although a
      type II statistical error cannot be excluded, due to the small size of the
      sample. The densities of PYY and Oxyntomodulin cells were significantly lower and
      that of somatostatin were significantly higher in IBS patients than controls.
      These abnormalities were observed in both IBS-D and IBS-C patients. The
      abnormalities in the endocrine cells observed in this study in the rectum
      differed considerably from those seen in the colon of IBS patients. This
      indicates that caution in using the rectum to represent the large intestine in
      these patients. These abnormalities could be primary (genetic) or secondary to
      changes in the gut hormones found in other segments of the gut and/or other
      pathological processes. Although the-cause-and effect relationship of the
      abnormalities found in rectal endocrine cells is difficult to elucidate, they
      might contribute to the symptoms associated with IBS. The densities of PYY and
      somatostatin cells are potential biomarkers with good sensitivity and specificity
      for the diagnosis of IBS. 

PMID- 24316399
TI  - The actions of neuropeptide SF on the hypothalamic-pituitary-adrenal axis and
      behavior in rats.
AB  - Present experiments focused on measuring the effect of neuropeptide SF (NPSF) on
      the hypothalamus-pituitary-adrenal (HPA) axis and behavior. The peptide was
      administered in different doses (0.25, 0.5, 1, 2 MUg) intracerebroventricularly
      to rats, and the behavior of which was then observed by telemetry and open-field
      test. Effect of NPSF on core temperature was also measured via telemetry. Plasma
      ACTH and corticosterone concentrations were measured to assess the influence of
      NPSF on the HPA activation. In addition, the changes in corticotrophin-releasing
      hormone (CRH) level in the hypothalamic paraventricular nucleus were continuously
      monitored by means of intracerebral microdialysis. Our results showed that NPSF
      augmented paraventricular CRH release and increased ACTH and corticosterone
      levels in the plasma. The release of corticosterone was successfully blocked by
      the pre-treatment of the CRH antagonist alpha-helical CRH9-41. Spontaneous and
      exploratory locomotor activity was also stimulated according to the telemetric
      and open-field studies. However, NPSF only tended to alter stereotyped behavior
      in the open-field experiments. These results demonstrate that NPSF may play a
      physiologic role in the regulation of such circadian functions as the activity of
      motor centers and the HPA axis, through the release of CRH.

PMID- 24316400
TI  - Structure and self-assembly of the calcium binding matrix protein of human
      metapneumovirus.
AB  - The matrix protein (M) of paramyxoviruses plays a key role in determining virion
      morphology by directing viral assembly and budding. Here, we report the crystal
      structure of the human metapneumovirus M at 2.8 A resolution in its native
      dimeric state. The structure reveals the presence of a high-affinity Ca2+ binding
      site. Molecular dynamics simulations (MDS) predict a secondary lower-affinity
      site that correlates well with data from fluorescence-based thermal shift assays.
      By combining small-angle X-ray scattering with MDS and ensemble analysis, we
      captured the structure and dynamics of M in solution. Our analysis reveals a
      large positively charged patch on the protein surface that is involved in
      membrane interaction. Structural analysis of DOPC-induced polymerization of M
      into helical filaments using electron microscopy leads to a model of M self
      assembly. The conservation of the Ca2+ binding sites suggests a role for calcium
      in the replication and morphogenesis of pneumoviruses.

PMID- 24316401
TI  - PKA RIalpha homodimer structure reveals an intermolecular interface with
      implications for cooperative cAMP binding and Carney complex disease.
AB  - The regulatory (R) subunit is the cAMP receptor of protein kinase A. Following
      cAMP binding, the inactive PKA holoenzyme complex separates into two active
      catalytic (C) subunits and a cAMP-bound R dimer. Thus far, only monomeric R
      structures have been solved, which fell short in explaining differences of cAMP
      binding for the full-length protein as compared to the truncated R subunits. Here
      we solved a full-length R-dimer structure that reflects the biologically relevant
      conformation, and this structure agrees well with small angle X-ray scattering.
      An isoform-specific interface is revealed between the protomers. This interface
      acts as an intermolecular sensor for cAMP and explains the cooperative character
      of cAMP binding to the RIalpha dimer. Mutagenesis of residues on this interface
      not only leads to structural and biochemical changes, but is also linked to
      Carney complex disease. 

PMID- 24316403
TI  - Equilibrium sampling approach to the interpretation of electron density maps.
AB  - The derivation of molecular models from spatial density data generated by X-ray
      crystallography or electron microscopy is an active field of research. Here, we
      introduce and evaluate an approach relying on the equilibrium sampling of energy
      landscapes describing restraints to experimental input data. Our procedure
      combines density restraints with replica exchange methodologies in the parameter
      space of the restraints, and we demonstrate its applicability to both flexible
      polymers and the assembly of protein complexes from rigid components. For the
      most difficult system studied, we highlight the importance of advanced data
      analysis techniques in mining poorly converged data further. Successful and
      unbiased interpretation of input density maps is a prerequisite for using this
      approach as an auxiliary restraint term in molecular simulations. Because these
      simulations will also utilize physical interaction potentials, we hope that they
      will contribute to deriving families of structural models for input data that are
      ambiguous per se. 

PMID- 24316402
TI  - Computing the relative stabilities and the per-residue components in protein
      conformational changes.
AB  - Protein molecules often undergo conformational changes. In order to gain insights
      into the forces that drive such changes, it would be useful to have a method that
      computes the per-residue contributions to the conversion free energy. Here, we
      describe the "confine-convert-release" (CCR) method, which is applicable to large
      conformational changes. We show that CCR correctly predicts the stable states of
      several "chameleon" sequences that have previously been challenging for molecular
      simulations. CCR can often discriminate better from worse predictions of native
      protein models in critical assessment of protein structure prediction (CASP). We
      show how the total conversion free energies can be parsed into per-residue free
      energy components. Such parsing gives insights into which amino acids are most
      responsible for given transformations. For example, here we are able to "reverse
      engineer" the known design principles of the chameleon proteins. This opens up
      the possibility for systematic improvements in structure-prediction scoring
      functions, in the design of protein conformational switches, and in interpreting
      protein mechanisms at the amino-acid level.

PMID- 24316404
TI  - Upregulation of Lhx8 increase VAChT expression and ACh release in neuronal cell
      line SHSY5Y.
AB  - Lhx8 is a transcription factor for cholinergic differentiation. Our previous
      experiments found upregulation of Lhx8 promoted cholinergic neuronal
      differentiation of hippocampal neural stem/progenitor cells or hippocampal
      newborn neurons in vitro. However, the role of Lhx8 in VAChT expression and ACh
      release is still less understood. In this report, we transfected Lhx8 cDNA into
      neuronal cell line SHSY5Y by lentiviral vectors to acquire the cells which stably
      expressed high level of Lhx8. Using this cell model, we provided experimental
      evidence that increasing Lhx8 upregulated the expression of ChAT and VAChT, and
      also increased the ACh release in culture medium. We suggested that Lhx8
      overexpression is a useful strategy to increase the release of ACh and maybe of
      therapeutic value to neurodegenerative diseases. 

PMID- 24316405
TI  - Evaluation of prosodic and segmental change in speech-modulated bone-conducted
      ultrasound by mismatch fields.
AB  - Speech-modulated bone-conducted ultrasound (BCU) can transmit speech sounds for
      some profoundly deaf individuals. Hearing aids using BCU are considered to be a
      novel hearing system for such individuals. In our previous study, the speech
      discrimination for speech-modulated BCU was objectively confirmed using a
      magnetoencephalography. Moreover, in our previous behavioral study, prosodic
      information for speech-modulated BCU could also be discriminated in the normal
      hearing. However, the prosodic discrimination for speech-modulated BCU has not
      objectively been studied. In order to evaluate the prosodic discrimination for
      speech-modulated BCU, mismatch fields (MMFs) elicited by prosodic and segmental
      change were measured for speech-modulated BCU and air-conducted speech. Ten
      Japanese participants with normal hearing took part in this study. Stimuli re
      synthesized from the speech of a native Japanese female adult were used. Standard
      stimulus was /itta/ with a flat pitch pattern, and two deviant stimuli were
      /itta?/ with a rising pitch pattern and /itte/ with a flat pitch pattern. All and
      nine participants elicited the prominent MMF elicited by the prosodic and
      segmental change for the speech-modulated BCU, respectively. The moment of MMF
      components for speech-modulated BCU was significantly smaller than those for air
      conducted speech, while no difference in the MMF latency elicited by the prosodic
      and segmental change were observed between both stimulus conditions. Comparing
      the MMFs elicited by prosodic and segmental change, no significant differences
      were observed for both stimulus conditions. Thus, it is suggested that the
      prosodic change can be discriminate to the same degree as segmental change even
      for speech-modulated BCU. However, discrimination capability for speech-modulated
      BCU is slightly inferior to that for air-conducted speech. 

PMID- 24316406
TI  - Spinal synaptic scaffolding protein Homer 1b/c regulates CREB phosphorylation and
      c-fos activation induced by inflammatory pain in rats.
AB  - Previous studies have shown that spinal Homer 1b/c plays an important role in the
      maintenance of chronic inflammatory pain induced by complete Freund's adjuvant
      (CFA). This study investigated the possible mechanism underlying Homer 1b/c
      mediating CFA-induced inflammatory pain. Chronic inflammation was induced by CFA
      injection into the left hind ankle of the rat. Homer 1b/c antisense or missense
      oligonucleotides were administered intrathecally (10MUg/10MUl) from 5 to 8 days
      following the onset of inflammation. Immunohistochemistry was conducted to detect
      the expression of phosphorylated cAMP response element binding protein (pCREB)
      and Fos protein in the spinal dorsal horn. Intrathecal administration of Homer
      1b/c antisense oligonucleotides not only markedly reduced the expression of Homer
      1b/c protein, but also attenuated CFA-induced inflammation, spinal CREB
      phosphorylation, and Fos expression. These results demonstrate for the first time
      that Homer 1b/c regulates CREB phosphorylation and c-fos activation in the spinal
      dorsal horn during the maintenance of chronic inflammatory pain, suggesting that
      Homer 1b/c may be involved in the development of CFA-induced inflammation. 

PMID- 24316408
TI  - Primary immunodeficiencies appearing as combined lymphopenia, neutropenia, and
      monocytopenia.
AB  - Recurrent or prolonged severe infections associated to panleukopenia strongly
      suggest primary immune disorders. In recent years, new immunodeficiency syndromes
      turned up: besides the importance of continuous clinical characterization
      throughout added reports, the phenotype can easily lead to diagnosis of known
      rare entities. Our purpose is to review main emerging genetic syndromes featuring
      lymphopenia combined to neutropenia and/or monocytopenia in order to facilitate
      diagnosis of rare primary immune deficiencies. 

PMID- 24316407
TI  - Regulatory dendritic cell therapy: from rodents to clinical application.
AB  - Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen
      presenting cells that induce or regulate innate and adaptive immunity. Regulatory
      or "tolerogenic" DC play a crucial role in maintaining self tolerance in the
      healthy steady-state. These regulatory innate immune cells subvert naive or
      memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit
      the ability to induce or restore T cell tolerance in many animal models of
      autoimmune disease or transplant rejection. There is also evidence that adoptive
      transfer of DCreg can regulate T cell responses in non-human primates and humans.
      Important insights gained from in vitro studies and animal models have led
      recently to the development of clinical grade human DCreg, with potential to
      treat autoimmune disease or enhance transplant survival while reducing patient
      dependency on immunosuppressive drugs. Phase I trials have been conducted in type
      1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility
      and safety of DCreg therapy. This mini-review will outline how observations made
      using animal models have been translated into human use, and discuss the
      challenges faced in further developing this form of regulatory immune cell
      therapy in the fields of autoimmunity and transplantation. 

PMID- 24316409
TI  - Interactive threats of nanoparticles to the biological system.
AB  - The use of nanoscale materials is growing exponentially, but concerns rise about
      the human hazards cannot be ignored. Nanotechnology has penetrated deep into our
      lives in diversified areas as engineering, information technology and
      diagnostics. Nonetheless owing to their peculiar properties these new materials
      also present new health risks upon interacting with biological systems. This is a
      typical case of technology preceding toxicity and therefore, various
      toxicological aspects for an array of nanomaterials are just beginning to be
      assessed. Several deleterious effects are being noticed, particularly in vitro
      situations as well as in mammalian system. Nanoparticles toxicity is compellingly
      related to oxidative stress, alteration of calcium homeostasis, gene expression,
      pro-inflammatory responses and cellular signalling events. It is therefore
      critical to understand the nature and origin of the toxicity imposed by
      nanomaterials. Keeping all these points in mind, the present review provides
      updated information on the various aspects such as sources of production, effect
      of different physical properties, interaction with biological system and
      mechanisms of engineered nanoparticles induced toxicities. 

PMID- 24316410
TI  - Younger apes and human children plan their moves in a maze task.
AB  - Planning defined as the predetermination of a sequence of actions towards some
      goal is crucial for complex problem solving. To shed light on the evolution of
      executive functions, we investigated the ontogenetic and phylogenetic origins of
      planning. Therefore, we presented all four great apes species (N=12) as well as 4
      and 5-year-old human preschoolers (N=24) with a vertical maze task. To gain a
      reward placed on the uppermost level of the maze, subjects had to move the reward
      to the bottom through open gaps situated at each level of the maze. In total,
      there were ten gaps located over three of the maze's levels, and free passage
      through these gaps could be flexibly blocked using multiple traps. Due to the
      decision tree design of the maze, the subjects had to plan their actions
      depending on the trap configuration up to two steps ahead to successfully
      retrieve the reward. We found that (1) our measure of planning was negatively
      correlated with age in nonhuman apes, (2) younger apes as well as 5-year-old
      children planned their moves up to two steps ahead whereas 4-year-olds were
      limited to plan one step ahead, and (3) similar performance but different
      underlying limitations between apes and children. Namely, while all species of
      nonhuman apes were limited by a lack of motor control, human children exhibited a
      shortage in shifting their attention across a sequence of subgoals. 

PMID- 24316411
TI  - E93 predominantly transduces 20-hydroxyecdysone signaling to induce autophagy and
      caspase activity in Drosophila fat body.
AB  - During the larval-prepupal transition in Drosophila, a balancing crosstalk occurs
      between autophagy and caspase activity in the remodeling fat body: the inhibition
      of autophagy induces caspase activity and the inhibition of caspases induces
      autophagy. Both autophagy and caspase activity are induced by a pulse of molting
      hormone (20-hydroxyecdysone, 20E) via the 20E nuclear receptor complex, EcR-USP.
      We here demonstrate that E93, a 20E primary-response gene encoding an HTH
      transcription factor, predominantly transduces 20E signaling to induce autophagy
      and caspase activity in the remodeling fat body. RNAi knockdown or mutation of
      E93 blocks autophagy and caspase activity, E93 overexpression induces them both,
      while E93 overexpression has a better rescuing effect on the inhibition of
      autophagy than caspase activity caused by EcR(DN) overexpression. At the
      transcriptional level, E93 not only greatly impacts the 20E-triggered
      transcriptional cascade, but also upregulates essential autophagy and apoptosis
      genes. Meanwhile, at the phosphorylational level, E93 blocks the PI3K-TORC1
      signaling to initiate autophagy. Taken together, we conclude that autophagy and
      caspase activity are induced by 20E and predominantly transduced by E93 in the
      remodeling fat body of Drosophila. 

PMID- 24316412
TI  - Molecular and functional characterization of CYP6BQ23, a cytochrome P450
      conferring resistance to pyrethroids in European populations of pollen beetle,
      Meligethes aeneus.
AB  - The pollen beetle (Meligethes aeneus F.) is widespread throughout much of Europe
      where it is a major coleopteran pest of oilseed rape (Brassica napus). The
      reliance on synthetic insecticides for control, particularly the pyrethroid
      class, has led to the development of populations with high levels of resistance.
      Resistance to pyrethroids is now widespread throughout Europe and is thought to
      be mediated by enhanced detoxification by cytochrome P450s and/or mutation of the
      pyrethroid target-site, the voltage-gated sodium channel. However, in the case of
      cytochrome P450 mediated detoxification, the specific enzyme(s) involved has
      (have) not yet been identified. In this study a degenerate PCR approach was used
      to identify ten partial P450 gene sequences from pollen beetle. Quantitative PCR
      was then used to examine the level of expression of these genes in a range of
      pollen beetle populations that showed differing levels of resistance to
      pyrethroids in bioassays. The study revealed a single P450 gene, CYP6BQ23, which
      is significantly and highly overexpressed (up to ~900-fold) in adults and larvae
      of pyrethroid resistant strains compared to susceptible strains. CYP6BQ23
      overexpression is significantly correlated with both the level of resistance and
      with the rate of deltamethrin metabolism in microsomal preparations of these
      populations. Functional recombinant expression of full length CYP6BQ23 along with
      cytochrome P450 reductase in an insect (Sf9) cell line showed that it is able to
      efficiently metabolise deltamethrin to 4-hydroxy deltamethrin. Furthermore we
      demonstrated by detection of 4-hydroxy tau-fluvalinate using ESI-TOF MS/MS that
      functionally expressed CYP6BQ23 also metabolizes tau-fluvalinate. A protein model
      was generated and subsequent docking simulations revealed the predicted substrate
      binding mode of both deltamethrin and tau-fluvalinate to CYP6BQ23. Taken together
      these results strongly suggest that the overexpression of CYP6BQ23 is the primary
      mechanism conferring pyrethroid resistance in pollen beetle populations
      throughout much of Europe. 

PMID- 24316413
TI  - Differences in practices of body stimulation during the first 3 months:
      ethnotheories and behaviors of Italian mothers and West African immigrant
      mothers.
AB  - This study investigated cultural differences, continuity and change of practices
      concerning body stimulation in a context of immigration. Parenting behaviors
      during the interaction with infants at 4, 8 and 12 weeks, and parenting
      ethnotheories at 12 weeks of first-generation West African immigrant mothers in
      Italy and autochthonous Italian mothers were compared. A qualitative inspection
      of ethnotheories using a thematic approach was included. As expected, results
      showed that immigrant mothers placed more emphasis on motor stimulation and
      showed longer durations of rhythmic motor and rhythmic tactile behaviors than
      Italian mothers; the latter placed more emphasis on tactile stimulation than
      immigrant mothers. The practice of motor stimulation in immigrant mothers was
      also adapted to values of the new context of life, becoming a positive
      interaction game with a mutual exchange of positive emotions. Findings express
      the complexity of a multidimensional process of acculturation. 

PMID- 24316414
TI  - Memory indexing of sequential symptom processing in diagnostic reasoning.
AB  - In diagnostic reasoning, knowledge about symptoms and their likely causes is
      retrieved to generate and update diagnostic hypotheses in memory. By letting
      participants learn about causes and symptoms in a spatial array, we could apply
      eye tracking during diagnostic reasoning to trace the activation level of
      hypotheses across a sequence of symptoms and to evaluate process models of
      diagnostic reasoning directly. Gaze allocation on former locations of symptom
      classes and possible causes reflected the diagnostic value of initial symptoms,
      the set of contending hypotheses, consistency checking, biased symptom processing
      in favor of the leading hypothesis, symptom rehearsal, and hypothesis change.
      Gaze behavior mapped the reasoning process and was not dominated by auditorily
      presented symptoms. Thus, memory indexing proved applicable for studying
      reasoning tasks involving linguistic input. Looking at nothing revealed memory
      activation because of a close link between conceptual and motor representations
      and was stable even after one week. 

PMID- 24316415
TI  - Can infants make transitive inferences?
AB  - Researchers have long been interested in the emergence of transitive reasoning
      abilities (e.g., if A>B and B>C, then A>C). Preschool-aged children are found to
      make transitive inferences. Additionally, nonhuman animals demonstrate parallel
      abilities, pointing to evolutionary roots of transitive reasoning. The present
      research examines whether 16-month-old infants can make transitive inferences
      about other people's preferences. If an agent prefers object-A over B (A>B) and B
      over C (B>C), infants seem to reason that she also prefers A over C (A>C)
      (Experiment 1). Experiment 2 provides indirect evidence that a one-directional
      linear ordering of the three items (A>B>C) may have helped infants to succeed in
      the task. These and control results present the first piece of evidence that
      precursors of transitive reasoning cognitive abilities exist in infancy. 

PMID- 24316416
TI  - Computational simulation of ligand docking to L-type pyruvate kinase subunit.
AB  - Computational blind docking approach was used for mapping of possible binding
      sites in L-type pyruvate kinase subunit for peptides, RRASVA and the
      phosphorylated derivative RRAS(Pi)VA, which model the phosphorylatable N-terminal
      regulatory domain of the enzyme. In parallel, the same docking analysis was done
      for both substrates of this enzyme, phosphoenolpyruvate (PEP) and adenosine
      diphosphate (ADP), and for docking of fructose 1,6-bisphosphate (FBP), which is
      the allosteric activator of the enzyme. The binding properties of the entire
      surface of the protein were scanned and several possible binding sites were
      identified in domains A and C of the protein, while domain B revealed no docking
      sites for peptides or for substrates or the allosteric regulator. It was found
      that the docking sites of different ligands were partially overlapping, pointing
      to the possibility that some regulatory effects, observed in the case of L-type
      pyruvate kinase, may be caused by the competition of different ligands for the
      same binding sites. 

PMID- 24316417
TI  - The orally available Btk inhibitor ibrutinib (PCI-32765) protects against
      osteoclast-mediated bone loss.
AB  - Bone-resorbing osteoclasts play an essential role in normal bone homeostasis, as
      well as in various bone disorders such as osteoporosis and rheumatoid arthritis.
      Previously we showed that the Tec family of tyrosine kinases is essential for the
      differentiation of osteoclasts and the inhibition of Btk is a promising strategy
      for the prevention of the bone loss in osteoclast-associated bone disorders. Here
      we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765),
      suppresses osteoclastic bone resorption by inhibiting both osteoclast
      differentiation and function. Ibrutinib downregulated the expression of NFATc1,
      the key transcription factor for osteoclastogenesis, and disrupted the formation
      of the actin ring in mature osteoclasts. In addition, genome-wide screening
      revealed that Btk regulates the expression of the genes involved in osteoclast
      differentiation and function in both an NFATc1-dependent and -independent manner.
      Finally, we showed that ibrutinib administration ameliorated the bone loss that
      developed in a RANKL-induced osteoporosis mouse model. Thus, this study suggests
      ibrutinib to be a promising therapeutic agent for osteoclast-associated bone
      diseases. 

PMID- 24316418
TI  - Ovariectomy enhances mechanical load-induced solute transport around osteocytes
      in rat cancellous bone.
AB  - To test if osteoporosis alters mechanical load-induced interstitial fluid flow in
      bone, this study examined the combined effect of estrogen deficiency and external
      loading on solute transport around osteocytes. An in vivo tracer, FITC-labeled
      bovine serum albumin, was injected into anesthetized ovariectomized and control
      female Sprague-Dawley rats before the right tibia was subjected to a controlled,
      physiological, non-invasive sinusoidal load to mimic walking. Tracer movement
      through the lacunar-canalicular system surrounding osteocytes was quantified in
      cortical and cancellous bone from the proximal tibia using confocal microscopy,
      with the non-loaded tibia serving as internal control. Overall, the application
      of mechanical loading increased the percentage of osteocyte lacunae labeled with
      injected tracer, and ovariectomy further enhanced movement of tracer. An analysis
      of separate regions demonstrated that ovariectomy enhanced in vivo transport of
      the injected tracer in the cancellous bone of the tibial epiphysis and metaphysis
      but not in the cortical bone of the metaphysis. These findings show that bone
      changes due to reduced estrogen levels alter convectional transport around
      osteocytes in cancellous bone and demonstrate a functional difference of
      interstitial fluid flow around osteocytes in estrogen-deficient rats undergoing
      the same physical activity as controls. The altered interstitial fluid flow
      around osteocytes is likely related to nanostructural matrix-mineral level
      differences recently demonstrated at the lacunar-canalicular surface of estrogen
      deficient rats, which could affect the transmission of mechanical loads to the
      osteocyte. 

PMID- 24316419
TI  - Disease severity and functional factors associated with walking performance in
      polyostotic fibrous dysplasia.
AB  - The purpose of this study was to determine the association between measures of
      disease severity, impairment, and ambulation ability in persons with polyostotic
      fibrous dysplasia (PFD). A cross-sectional sample of 81 patients (ages 5-57) with
      polyostotic fibrous dysplasia was evaluated as part of an ongoing study. Subjects
      were scored on the Skeletal Disease Burden Score (SDBS), completed a 9-minute
      walk test (9MW), manual muscle testing (MMT), and measurements of range of motion
      (ROM). Correlations between continuous variables were calculated using the
      Pearson correlation coefficient and ordinal variables by Spearman correlation
      coefficient. It was found that subjects with more severe disease walked slower
      than those with less skeletal disease, with the exception of the youngest
      subjects. Walking velocity was faster in subjects with better hip strength and
      range of motion and slower in those with bilateral coxa vara. Those subjects with
      more severe disease had less range of motion, were weaker at the hips, and more
      likely to have leg length discrepancy. Skeletal disease severity was associated
      with hip weakness, leg length discrepancy, and loss of range of motion. In most
      cases, findings did not differ in the presence or absence of associated
      endocrinopathies. Skeletal disease severity, MMT and ROM each has an impact on
      walking efficiency in persons with PFD. These findings suggest that treatment
      focused on strategies to improve or, at least, maintain hip strength and range of
      motion, correct leg length discrepancies and hip malalignment may help preserve
      ambulation ability in persons with PFD and that treatment should begin at a young
      age. 

PMID- 24316420
TI  - Deletion of Mecom in mouse results in early-onset spinal deformity and
      osteopenia.
AB  - Recent studies have indicated a role for a MECOM allele in susceptibility to
      osteoporotic fractures in humans. We have generated a mutation in Mecom in mouse
      (termed ME(m1)) via lacZ knock-in into the upstream transcription start site for
      the gene, resulting in disruption of Mds1 and Mds1-Evi1 transcripts, but not of
      Evi1 transcripts. We demonstrate that ME(m1/m1) mice have severe kyphoscoliosis
      that is reminiscent of human congenital or primary kyphoscoliosis. ME(m1/m1) mice
      appear normal at birth, but by 2weeks, they exhibit a slight lumbar lordosis and
      narrowed intervertebral space. This progresses to severe lordosis with disc
      collapse and synostosis, together with kyphoscoliosis. Bone formation and
      strength testing show that ME(m1/m1) mice have normal bone formation and
      composition but are osteopenic. While endochondral bone development is normal, it
      is markedly dysplastic in its organization. Electron micrographs of the 1week
      postnatal intervertebral discs reveals marked disarray of collagen fibers,
      consistent with an inherent weakness in the non-osseous connective tissue
      associated with the spine. These findings indicate that lack of ME leads to a
      complex defect in both osseous and non-osseous musculoskeletal tissues, including
      a marked vertebral osteopenia, degeneration of the IVD, and disarray of
      connective tissues, which is likely due to an inherent inability to establish
      and/or maintain components of these tissues. 

PMID- 24316421
TI  - Imaging of thrombosis and microcirculation in mouse lungs of initial melanoma
      metastasis with in vivo cryotechnique.
AB  - Microscopic bioimaging of blood flow and distribution of cancer cells in lungs is
      essential to analyze mechanism of lung metastasis. Such cancer metastasis has
      been well known to induce hypercoagulable states and thrombosis. In
      histopathological tissue sections, however, it has been difficult to capture
      rapid phenomenon of thrombus formation due to technical problems associated with
      much less retention of soluble serum components as well as dynamic histological
      features reflecting their living states. In this study, to achieve bioimaging of
      both hypercoagulable states and thrombosis induced by early metastasis of mouse
      B16-BL6 melanoma, "in vivo cryotechnique" (IVCT) was used, which retained soluble
      components at their original sites. Glutathione-coated quantum dots (QDs) were
      subsequently injected after melanoma cells via right ventricles to examine plasma
      flow with fluorescence emission. At 5s after the melanoma injection, melanoma
      cells were mostly stacked and intruded in alveolar capillaries with changing
      their shapes. Assembly of platelets initially appeared at 1min, and they
      aggregated around the stacked melanoma cells at 5min. Such aggregated platelets
      were immunopositive for both phospho-tyrosine 418 and 527 of Src, indicating
      their partial signal activation. Fibrin monomers were also immunolocalized around
      both melanoma cells and platelet aggregates, and massive immunoreaction deposits
      of fibrinogen were also detected near the same areas, but more strongly detected
      around the melanoma cells, indicating initial thrombus formation. In those areas,
      QDs were rarely detected, probably because of the lack of blood supply. Thus,
      IVCT revealed histopathological features of initial thrombosis under their
      circulatory conditions. 

PMID- 24316422
TI  - Objective area measurement technique for choroidal neovascularization from
      fluorescein angiography.
AB  - The purpose of this study was to develop a non-biased method of quantitatively
      measuring choroidal neovascularization (CNV) areas based on late-phase
      fluorescein angiography (FA) images. Experimental CNV was induced in Long Evans
      rats by laser disruption of the Bruch's membrane. FA was performed weekly for
      5weeks. Multi-Otsu thresholding (MOT) was used to quantify CNV in late-phase FA
      images from both experimental rodent CNV and wet age-related macular degeneration
      (wAMD) patients. Images were automatically thresholded into three levels based on
      the image histogram, with the highest level containing CNV. To determine the
      technique's ability to quantify CNV areas, rats were given either triamcinolone
      acetonide or dexamethasone sodium phosphate to treat CNV and compared to
      untreated rats. The rat CNV lesion areas measured from 5-week histology sections
      from each treatment group were compared to areas measured from the corresponding
      FA images. MOT was able to detect statistical decreases in rodent CNV area in the
      treatment groups versus control from weeks 3 through 5. The ratio of CNV area
      measured from histology to area measured from FA images was not statistically
      different between groups. Finally, to determine the usefulness of MOT on
      pathological morphologies of CNV, MOT was performed on late-phase FA images from
      patients with classic and diffuse CNV. The technique was able to segment
      classical CNV in wAMD patients, but performed poorly with diffuse CNV. MOT
      provides a robust, objective, and quantifiable area measurement of CNV lesion
      area in both experimentally-induced and pathological CNV. The results indicate
      that MOT could be a useful research tool in helping evaluate the effects of
      therapeutics on CNV growth. 

PMID- 24316423
TI  - Characterization of potential degradation products in a PEGylating reagent 20 kDa
      monomethoxy polyethylene glycol propionaldehyde by RP-HPLC, APCI-MS and NMR.
AB  - Ensuring quality of PEGylating reagents is essential for the successful
      development and manufacturing of PEGylated biopharmaceuticals. However, little is
      known about how to maintain and verify the quality of PEG raw materials for
      PEGylated protein manufacturing. In this study, monomethoxy polyethylene glycol
      propionaldehyde (mPEG-aldehyde) was subjected to conditions that mimic
      accelerated stability conditions. Separation of trace-level degradation products
      in the presence of mPEG-aldehyde was achieved by derivatization with 2,4
      dinitrophenylhydrazine (DNPH), followed by reversed phase high performance liquid
      chromatography with ultraviolet detection (RP-HPLC-UV) at 355nm. Structural
      characterization by atmospheric pressure chemical ionization mass spectrometry
      (APCI-MS) identified formaldehyde, acetaldehyde, crotonaldehyde, acrolein,
      benzaldehyde, and tolualdehyde as major degradation products or process-related
      impurities. The presence of formaldehyde and acrolein was confirmed by (1)H NMR
      in the forced degraded mPEG-aldehyde samples without derivatization of mPEG
      aldehyde. Findings from this study imply that reactive impurities could form as a
      result of inappropriate mPEG-aldehyde handling or storage. Further, a rapid
      screening method based on reversed phase HPLC was shown to be an effective
      screening assay used for routine screening of mPEG-aldehyde to ensure consistent
      PEGylated protein product quality. 

PMID- 24316424
TI  - Improved liquid-liquid extraction with inter-well volume replacement dilution
      workflow and its application to quantify BMS-927711 in rat dried blood spots by
      UHPLC-MS/MS.
AB  - An UHPLC-MS/MS method was developed and validated to quantify BMS-927711, a drug
      candidate to treat migraine, in rat dried blood spots (DBS). The DBS samples were
      extracted using an improved liquid-liquid extraction (LLE) strategy involving in
      the sonication of DBS punches in 20% MeOH aqueous solution containing the
      internal standard, [(13)C2, D4]-BMS-927711, and then with a 100mM NH4OAc buffer
      solution, followed by an automated LLE with EtOAc-hexane (70:30, v/v). The
      presence of 20% MeOH as an organic modifier in the elution solution significantly
      improved the analyte elution efficiency and assay performance. A novel inter-well
      volume replacement dilution workflow was introduced for DBS sample dilution
      before LLE step. This was a simple two-step process, firstly a small portion of
      the DBS blank solution was discarded, and then the same volume of a concentrated
      DBS sample solution was spiked into the leftover blank solution to achieve a
      desired dilution. Chromatographic separation was achieved on an Acuity UPLC((r))
      BEH C18 column (2.1mm*50mm, 1.7MUm) and the analyte was detected by selected
      reaction monitoring (SRM) with positive electrospray ionization on an AB Sciex
      Triple Quad 5500 mass spectrometer. The standard curve was linear from 5.00 to
      5000ng/mL with assay precision <=4.9% CV, and assay accuracy within +/-3.1%Dev of
      the nominal values. Accurate sample dilution was achieved by using inter-well
      volume replacement with a precision of <=4.2% CV and an accuracy of +/-3.3% for
      dilution QC at 50,000ng/mL with 100-fold dilution (n=18). This robust UHPLC-MS/MS
      assay has been successfully applied to the non-clinical studies in rats. By using
      inter-well volume replacement workflow, accurate dilution was demonstrated using
      only one DBS blank sample for a typical dilution of <50-fold, and using only two
      blank DBS samples for a dilution of up to 625-fold. Moreover, this new workflow
      makes it easier to automate DBS sample dilution. 

PMID- 24316425
TI  - Pharmacokinetics of plantamajoside and acteoside from Plantago asiatica in rats
      by liquid chromatography-mass spectrometry.
AB  - Plantago asiatica is a medicinal and dietary plant rich in polyphenolic compounds
      such as phenylpropanoid glycosides plantamajoside and acteoside. The aims of the
      present study were to develop a new and sensitive method for simultaneous
      determination of plantamajoside and acteoside and investigate their
      pharmacokinetic properties in rats. A sensitive and rapid liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method with multiple-reaction monitoring
      (MRM) mode was employed for quantification of two analytes in rat plasma. The
      calibration curve was linear over the range of 0.2-200ng/ml with correlation
      coefficient greater than 0.9983 for both analytes. The accuracy of plantamajoside
      and acteoside were between -4.2% and 8.1%, -3.8% and 8.9% relative error,
      respectively. Precision for the two analytes ranged from 2.7 to 10.2% relative
      standard deviation. The pharmacokinetic results showed plantamajoside and
      acteoside were quickly absorbed in rat with the time to maximum plasma
      concentration 16.7+/-2.8 and 13.3+/-2.8min, respectively. The elimination
      constants were 0.28+/-0.01 1h(-1) for plantamajoside and 0.47+/-0.03 1h(-1) for
      acteoside. The developed method and the pharmacokinetic data provide a basis for
      further studies on bioactivity of P. asiatica. 

PMID- 24316426
TI  - Metabolite profiling of polyphenols in Vaccinium berries and determination of
      their chemopreventive properties.
AB  - A detailed investigation on the chemical composition and chemopreventive activity
      of Vaccinium floribundum Kunth berries was carried out in comparison with
      Vaccinium myrtillus L. Berry polyphenols were extracted by using two sequential
      dynamic maceration steps, which enabled to maximize the yields of secondary
      metabolites. In particular, phenolic acids and flavonols were extracted from
      berries using ethyl acetate (EtOAc), whereas anthocyanins were extracted from the
      residue with 0.6M HCl in methanol (MeOH). The analysis of secondary metabolites
      in berry extracts was performed by means of two specific HPLC methods. Phenolic
      acids and flavonols were analyzed on an Ascentis C18 column (250mm*4.6mm I.D.,
      5MUm), with a gradient mobile phase composed of 0.1M HCOOH in H2O and ACN.
      Anthocyanin analysis was carried out on a Zorbax SB-C18 column (150mm*4.6mm I.D.,
      5MUm), with a gradient mobile phase composed of H2O-HCOOH (9:1, v/v) and MeOH-H2O
      HCOOH (5:4:1, v/v/v). Detection was performed by UV/DAD, MS and MS(2). The
      polyphenol composition of V. floribundum and V. myrtillus was studied in detail.
      The samples of V. floribundum analyzed in this study had a much higher content of
      both phenolic acids and flavonols in comparison with V. myrtillus (mean value
      41.6+/-10.2 and 13.7+/-0.2mg/100g FW, respectively), while V. myrtillus showed a
      higher amount of anthocyanins if compared with V. floribundum (568.8+/-8.8 and
      mean value 376.2+/-49.9mg/100gFW, respectively). The extracts gave negative
      results in antimutagenic assays against carcinogens 2-amino-3,4
      dimethylimidazo[4,5-f]quinoline (MeIQ) and 4-nitroquinoline-1-oxide (4-NQO),
      while they performed similarly in both ABTS(+) and DPPH antioxidant assays. 

PMID- 24316427
TI  - Sensitive derivatization methods for the determination of genotoxic impurities in
      drug substances using hyphenated techniques.
AB  - Six sensitive derivatization methods for the determination of genotoxic
      impurities in selected drug substances were developed using hyphenated
      techniques. Some of the raw materials, reagents and reaction intermediates of the
      selected drug substances were identified as genotoxic impurities through DEREK
      software for windows. The genotoxic impurities which are amenable for
      derivatization were selected as substrates. Derivatizing agents were selected
      based on the functional groups of the genotoxic impurities. The chemistry
      involved in the derivatization was explained with suitable mechanisms. An
      appropriate hyphenated technique viz. LC-MS and GC-MS was opted based on the
      sensitivity and aromaticity of the derivatized genotoxic impurities. All the
      methods were validated as per International Conference on Harmonization
      guidelines. Correlation coefficient values were found about 0.99. The obtained %
      R.S.D values from replicate injections in the range of 2.3-4.8 and % recoveries
      of the added impurities in the range of 83.7-101.7 ensured the precision and
      accuracy, respectively. 

PMID- 24316428
TI  - Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in
      endothelial cells.
AB  - Endothelial dysfunction associated with vitamin D deficiency has been linked to
      many chronic vascular diseases. Vitamin D elicits its bioactive actions by
      binding to its receptor, vitamin D receptor (VDR), on target cells and organs. In
      the present study, we investigated the role of VDR in response to 1,25(OH)2D3
      stimulation and oxidative stress challenge in endothelial cells. We found that
      1,25(OH)2D3 not only induced a dose- and time-dependent increase in VDR
      expression, but also induced up-regulation of vascular endothelial growth factor
      (VEGF) and its receptors (Flt-1 and KDR), as well as antioxidant CuZn-superoxide
      dismutase (CuZn-SOD) expression in endothelial cells. We demonstrated that
      inhibition of VDR by VDR siRNA blocked 1,25(OH)2D3 induced increased VEGF and KDR
      expression and prevented 1,25(OH)2D3 induced endothelial proliferation/migration.
      Using CoCl2, a hypoxic mimicking agent, we found that hypoxia/oxidative stress
      not only reduced CuZn-SOD expression, but also down-regulated VDR expression in
      endothelial cells, which could be prevented by addition of 1,25(OH)2D3 in
      culture. These findings are important indicating that VDR expression is inducible
      in endothelial cells and oxidative stress down-regulates VDR expression in
      endothelial cells. We conclude that sufficient vitamin D levels and proper VDR
      expression are fundamental for angiogenic and oxidative defense function in
      endothelial cells.

PMID- 24316429
TI  - Cell cycle arrest and apoptosis induced by 1alpha,25(OH)2D3 and TX 527 in Kaposi
      sarcoma is VDR dependent.
AB  - We have previously shown that 1alpha,25(OH)2-Vitamin D3 [1alpha,25(OH)2D3] and
      its less calcemic analog TX 527 inhibit the proliferation of endothelial cells
      transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma
      (vGPCR) and this could be partially explained by the inhibition of the NF-kappaB
      pathway. In this work, we further explored the mechanism of action of both
      vitamin D compounds in Kaposi sarcoma. We investigated whether the cell cycle
      arrest and subsequent apoptosis of endothelial cells (SVEC) and SVEC transformed
      by vGPCR (SVEC-vGPCR) elicited by 1alpha,25(OH)2D3 and TX 527 were mediated by
      the vitamin D receptor (VDR). Cell cycle analysis of SVEC and SVEC-vGPCR treated
      with 1alpha,25(OH)2D3 (10nM, 48h) revealed that 1alpha,25(OH)2D3 increased the
      percentage of cells in the G0/G1 phase and diminished the percentage of cells in
      the S phase of the cell cycle. Moreover, the number of cells in the S phase was
      higher in SVEC-vGPCR than in SVEC due to vGPCR expression. TX 527 exerted similar
      effects on growth arrest in SVEC-vGPCR cells. The cell cycle changes were
      suppressed when the expression of the VDR was blocked by a stable transfection of
      shRNA against VDR. Annexin V-PI staining demonstrated apoptosis in both SVEC and
      SVEC-vGPCR after 1alpha,25(OH)2D3 and TX 527 treatment (10nM, 24h). Cleavage of
      caspase-3 detected by Western blot analysis was increased to a greater extent in
      SVEC than in SVEC-vGPCR cells, and this effect was also blocked in VDR knockdown
      cells. Altogether, these results suggest that 1alpha,25(OH)2D3 and TX 527 inhibit
      the proliferation of SVEC and SVEC-vGPCR and induce apoptosis by a mechanism that
      involves the VDR. 

PMID- 24316430
TI  - Human pharmacokinetic profile of 1,25-dihydroxyvitamin D3-glycoside of herbal
      origin.
AB  - A natural form of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite
      of vitamin D, was identified in glycosylated form in Solanum glaucophyllum (SG).
      Solbone P, an extract of SG with high and homogenous content of glycosylated
      1,25(OH)2D3, was chemically characterized and produced under GMP conditions.
      Three different doses of glycosylated 1,25(OH)2D3 were given as single oral dose
      to 16 healthy volunteers in a first-in-man trial. The oral pharmacokinetic
      properties of 1,25(OH)2D3 of SG origin were established and the subjects were
      monitored until day 28 for safety reasons. This included regular monitoring of
      vital signs, electrocardiogram (ECG) data, calcium, phosphate and creatinine
      values. Subjects were exposed to up to the equivalent of a 40-fold level of the
      recommended human daily dose for synthetic 1,25(OH)2D3 (0.5MUg/subject/day)
      without experiencing any untoward effects. When compared with the historically
      established pharmacokinetics profile of synthetic 1,25(OH)2D3, glycosylated
      1,25(OH)2D3 of herbal origin exhibited delayed absorption characteristics. The
      phenomenon is species independent, as similar pharmacokinetic patterns were
      observed in rats and chickens. This modified release pattern may be attributed to
      the glycosylation of herbal 1,25(OH)2D3 because de-glycosylation by ubiquitous
      intestinal enzymes prior to intestinal uptake of the unmodified 1,25(OH)2D3 is
      the rate-limiting step. The major relevance of this finding is that the human
      pharmacokinetic profile of glycosylated 1,25(OH)2D3 of herbal origin is
      reminiscent of a delayed release formulation of free 1,25(OH)2D3, resulting in a
      wider therapeutic window, a potentially longer therapeutic effectiveness, and
      thus, a better pharmacologic tolerance. This article is part of a Special Issue
      entitled '16th Vitamin D Workshop'. 

PMID- 24316431
TI  - Down-regulation of Zac1 gene expression in rat white adipose tissue by androgens.
AB  - ZAC1 is a zinc-finger protein transcription factor, a transcriptional cofactor
      for nuclear receptors, and a co-activator of nuclear receptors, which interacts
      with multiple signaling pathways affecting apoptosis, cell cycle arrest, and
      metabolism. Some data suggest that ZAC1 regulates the expression of genes
      associated with function of adipose tissue. Since there is no information about
      the levels of Zac1 gene expression in white adipose tissue (WAT), and the
      expression of several genes associated with metabolic function of WAT is
      significantly lower in male than female animals, we have examined: (a) the
      relative ZAC1 mRNA levels in some organs/tissues, including three main depots of
      WAT, in 3-month-old male rats; (b) the relative ZAC1 mRNA levels in WAT of male
      and female rats; (c) the effect of orchidectomy and orchidectomy with concomitant
      testosterone treatment on ZAC1 mRNA and protein levels; (d) the effect of
      ovariectomy and ovariectomy with concomitant 17beta-estradiol treatment on ZAC1
      mRNA levels; (e) the effect of dihydrotestosterone on ZAC1 mRNA levels in
      isolated adipocytes. Our results indicate that: (a) ZAC1 mRNA levels are
      relatively high in WAT in comparison with other organs/tissues; (b) ZAC1 mRNA
      levels in subcutaneous WAT are approximately 2-fold lower than in epididymal and
      retroperitoneal adipose tissue; (c) ZAC1 mRNA levels in WAT of adult female rats
      are approximately 2-fold higher than in male rats; (d) testosterone is inversely
      related to ZAC1 mRNA and protein levels in WAT of male rats; and (e)
      dihydrotestosterone decreases the ZAC1 mRNA levels in adipocytes in dose
      dependent manner. In conclusion, Zac1 gene is highly expressed in white adipose
      tissue of adult rats. Androgens could play an important role in down-regulation
      of the ZAC1 mRNA and protein levels in rats. 

PMID- 24316433
TI  - A designed equine herpes thymidine kinase (EHV4 TK) variant improves ganciclovir
      induced cell-killing.
AB  - The limitations of the ganciclovir (GCV)/herpes simplex virus thymidine kinase
      (HSV1 TK: EC 2.7.1.21) system as a suicide gene therapy approach have been
      extensively studied over the years. In our study, we focused on improving the
      cytotoxic profile of the GCV/equine herpes virus-4 thymidine kinase (EHV4 TK: EC
      2.7.1.21) system. Our approach involved the structure-guided mutagenesis of EHV4
      TK in order to switch its ability to preferentially phosphorylate the natural
      substrate deoxythymidine (dT) to that of GCV. We performed steady-state kinetic
      analysis, genetic complementation in a thymidine kinase-deficient Escherichia
      coli strain, isothermal titration calorimetry, and analysis of GCV-induced cell
      killing through generation of HEK 293 stable cell-lines expressing EHV4 TK
      mutants and wild-type EHV4 TK. We found that the EHV4 TK S144H-GFP mutant
      preferentially phosphorylates GCV and confers increased GCV-induced cytotoxicity
      compared to wild-type EHV4 TK. 

PMID- 24316432
TI  - A tetra(ethylene glycol) derivative of benzothiazole aniline ameliorates
      dendritic spine density and cognitive function in a mouse model of Alzheimer's
      disease.
AB  - We recently reported that the tetra(ethylene glycol) derivative of benzothiazole
      aniline, BTA-EG4, acts as an amyloid-binding small molecule that promotes
      dendritic spine density and cognitive function in wild-type mice. This raised the
      possibility that BTA-EG4 may benefit the functional decline seen in Alzheimer's
      disease (AD). In the present study, we directly tested whether BTA-EG4 improves
      dendritic spine density and cognitive function in a well-established mouse model
      of AD carrying mutations in APP, PS1 and tau (APPswe;PS1M146V;tauP301L, 3xTg AD
      mice). We found that daily injections of BTA-EG4 for 2 weeks improved dendritic
      spine density and cognitive function of 3xTg AD mice in an age-dependent manner.
      Specifically, BTA-EG4 promoted both dendritic spine density and morphology
      alterations in cortical layers II/III and in the hippocampus at 6-10 months of
      age compared to vehicle-injected mice. However, at 13-16 months of age, only
      cortical spine density was improved without changes in spine morphology. The
      changes in dendritic spine density correlated with Ras activity, such that 6-10
      month old BTA-EG4 injected 3xTg AD mice had increased Ras activity in the cortex
      and hippocampus, while 13-16 month old mice only trended toward an increase in
      Ras activity in the cortex. Finally, BTA-EG4 injected 3xTg AD mice at 6-10 months
      of age showed improved learning and memory; however, only minimal improvement was
      observed at 13-16 months of age. This behavioral improvement corresponds to a
      decrease in soluble Abeta 40 levels. Taken together, these findings suggest that
      BTA-EG4 may be beneficial in ameliorating the synaptic loss seen in early AD.

PMID- 24316434
TI  - Mitochondrial respiration as a target for neuroprotection and cognitive
      enhancement.
AB  - This paper focuses on brain mitochondrial respiration as a therapeutic target for
      neuroprotection and cognitive enhancement. We propose that improving brain
      mitochondrial respiration is an important future direction in research and
      treatment of Alzheimer's disease (AD) and other conditions associated with
      cognitive impairment and neurodegeneration. The central thesis is that supporting
      and improving brain mitochondrial respiration constitutes a promising
      neurotherapeutic principle, with potential applications in AD as well as in a
      wide variety of neuropsychological conditions. We propose three different
      interventional approaches to improve brain mitochondrial respiration based on (a)
      pharmacology, (b) photobiomodulation and (c) nutrition interventions, and provide
      detailed examples for each type of intervention. First, low-dose USP methylene
      blue is described as a pharmacological intervention that can successfully
      increase mitochondrial respiration and result in memory enhancement and
      neuroprotection. Second, transcranial low-level light/laser therapy with near
      infrared light is used to illustrate a photobiomodulation intervention with
      similar neurometabolic mechanisms of action as low-dose methylene blue. Finally,
      a nutrition intervention to improve mitochondrial respiration is proposed by
      increasing ketone bodies in the diet. The evidence discussed for each
      intervention supports a fundamental neurotherapeutic strategy based on improving
      oxidative energy metabolism while at the same time reducing the pro-oxidant
      tendencies of the nervous system. Targeting brain mitochondrial respiration with
      these three types of interventions is proposed as part of a holistic
      neurotherapeutic approach to improve brain energy metabolism and antioxidant
      defenses. This strategy represents a promising new bioenergetics direction for
      treatment of AD and other neuropsychological disorders featuring cognitive
      impairment and neurodegeneration. 

PMID- 24316435
TI  - Inhibition of P-glycoprotein in the blood-brain barrier alters avermectin
      neurotoxicity and swimming performance in rainbow trout.
AB  - The importance of the blood brain barrier (BBB) and the contribution to its
      function by the efflux transporter P-glycoprotein (P-gp) in teleosts were
      examined using the P-gp substrates and central nervous system neurotoxins
      ivermectin (22,23-dihydroavermectin B1a+22,23-dihydroavermectin B1b) [IVM]) and
      emamectin benzoate (4"-deoxy-49"epimethylaminoavermectin B1 benzoate [EB]). Trout
      were injected intraperitoneally with 0.01-1.0 and 1-50mg/kg of IVM or EB,
      respectively either alone or in combination with cyclosporin A (CsA: a P-gp
      substrate) at 1mg/kg. IVM affected the swimming performance (critical swimming
      speed, burst swimming distance, and schooling) at significantly lower
      concentrations than EB. When fish were exposed to IVM or EB in the presence of
      CsA, alterations to swimming were increased, suggesting that competition for P-gp
      in the BBB by CsA increased IVM and EB penetration into the CNS and decreased
      swimming capabilities. The effect of co-administration of CsA on swimming-related
      toxicity was different between IVM and EB-treated fish; EB toxicity was increased
      to a greater extent than IVM toxicity. The greater chemosensitization effect of
      EB vs. IVM was examined using a P-gp competitive inhibition assay in isolated
      trout hepatocytes with rhodamine 123 as a substrate. At the cellular level, IVM
      was a more potent inhibitor of P-gp than EB, which allowed for a greater
      accumulation of R123 in hepatocytes. These results provide evidence for a role of
      P-gp in the BBB of fish, and suggest that this protein protects fish from
      environmental neurotoxins.

PMID- 24316436
TI  - Oxidative stress parameters induced by exposure to either cadmium or 17beta
      estradiol on Mytilus galloprovincialis hemocytes. The role of signaling
      molecules.
AB  - The aim of the present study was to determine and compare the possible effects of
      exposure to an estrogen, 17beta-estradiol and to a metal, cadmium on oxidative
      parameters of Mytilus galloprovincialis hemocytes and to elucidate the signaling
      pathways that probably mediate the studied effects exerted by these two
      chemicals. In addition, it was of interest to investigate if the studied
      parameters could constitute biomarkers for aquatic pollution monitoring. Our
      results suggest that micromolar concentrations of either cadmium or 17beta
      estradiol affected the redox status of mussels by modulating oxidative parameters
      and antioxidant enzymes gene expression in mussel M. galloprovincialis hemocytes.
      In particular, our results showed that treatment of hemocytes with either 5 MUM
      of cadmium chloride or with 25 nM of 17beta-estradiol for 30 min caused
      significant increased ROS production; this led to oxidative damage exemplified by
      significant increased DNA damage, protein carbonylation and lipid peroxidation,
      as well as increased mRNA levels of the antioxidant enzymes catalase (CAT),
      superoxide dismoutase (SOD) and glutathione S-transferase (GST). Furthermore, our
      results suggest that either cadmium or 17beta-estradiol signal is mediated either
      through one of the already known pathways initiated by photatidyl-inositol 3
      kinase (PI3K) and reaching Na(+)/H(+) exchanger (NHE) probably through protein
      kinase C (PKC) or a kinase-mediated signaling pathway that involves in most of
      the cases NHE, PKC, Ca(2+)-dependent PKC isoforms, PI3-K, NADPH oxidase, nitric
      oxide (NO) synthase, c-Jun N-terminal kinase (JNK) and cyclic adenosine-3'-5'
      monophosphate (cAMP). Our results also attribute a protective role to cAMP, since
      pre-elevated intracellular cAMP levels inhibited the signal induced by each
      exposure. Finally, since aquatic invertebrates have been the most widely used
      monitoring organisms for pollution impact evaluation in marine environments and
      taking under consideration the positive correlation obtained between the studied
      parameters, we can suggest the simultaneous use of these oxidative stress
      parameters offering an effective early warning system in biomonitoring of aquatic
      environments.

PMID- 24316437
TI  - Embryonic arsenic exposure reduces the number of muscle fibers in killifish
      (Fundulus heteroclitus).
AB  - Arsenic is a contaminant of drinking water and has been correlated with adverse
      developmental outcomes such as low birth weight, reduced weight gain, and altered
      locomotor activity. Previous research has shown that killifish (Fundulus
      heteroclitus) exposed to high arsenic levels during embryogenesis had smaller
      muscle fiber diameters. The current study was designed to determine whether
      changes in muscle fibers persisted, were exacerbated, or resolved over time.
      Killifish embryos were exposed to 0-5 ppm arsenite and, upon hatching, were
      transferred into either clean water or continued receiving the same exposure to
      arsenic for up to 16 weeks. Arsenic significantly decreased the weight of both
      embryonic-only exposed juveniles and continuously exposed juveniles between 4 and
      16 weeks of development at concentrations as low as 0.8 ppm. Although arsenite
      exposure increased the percentage of small diameter fibers during the early
      weeks, fiber diameters returned to control levels in the embryonic-only exposed
      fish. However, muscle fiber density was still reduced to 85.7%, 80.3%, and 73.8%
      of control for the 0.8, 2, and 5 ppm embryonic-only exposure groups,
      respectively, even after 16 weeks of development. These results indicate that
      while continuous exposure to arsenic may alter the size of muscle fibers,
      embryonic-only exposure to arsenic has lasting effects on the number of muscle
      fibers formed.

PMID- 24316438
TI  - Uptake, transfer and elimination kinetics of paralytic shellfish toxins in common
      octopus (Octopus vulgaris).
AB  - Marine phycotoxins derived from harmful algal blooms are known to be associated
      with mass mortalities in the higher trophic levels of marine food webs. Bivalve
      mollusks and planktivorous fish are the most studied vectors of marine
      phycotoxins. However, field surveys recently showed that cephalopod mollusks also
      constitute potential vectors of toxins. Thus, here we determine, for the first
      time, the time course of accumulation and depuration of paralytic shellfish
      toxins (PSTs) in the common octopus (Octopus vulgaris). Concomitantly, the
      underlying kinetics of toxin transfer between tissue compartments was also
      calculated. Naturally contaminated clams were used to orally expose the octopus
      to PSTs during 6 days. Afterwards, octopus specimens were fed with non
      contaminated shellfish during 10 days of depuration period. Toxins reached the
      highest concentrations in the digestive gland surpassing the levels in the kidney
      by three orders of magnitude. PSTs were not detected in any other tissue
      analyzed. Net accumulation efficiencies of 42% for GTX5, 36% for dcSTX and 23%
      for C1+2 were calculated for the digestive gland. These compounds were the most
      abundant toxins in both digestive gland and the contaminated shellfish diet. The
      small differences in relative abundance of each toxin observed between the prey
      and the cephalopod predator indicates low conversion rates of these toxins. The
      depuration period was better described using an exponential decay model
      comprising a single compartment - the entire viscera. It is worth noting that
      since octopuses' excretion and depuration rates are low, the digestive gland is
      able to accumulate very high toxin concentrations for long periods of time.
      Therefore, the present study clearly shows that O. vulgaris is a high-potential
      vector of PSTs during and even after the occurrence of these toxic algal blooms. 

PMID- 24316439
TI  - Facile production of ZnS quantum dot nanoparticles by Saccharomyces cerevisiae
      MTCC 2918.
AB  - Microbial synthesis of nanoparticles is a green route towards ecofriendly
      measures to overcome the toxicity and non-applicability of nanomaterials in
      clinical uses obtained by conventional physical and chemical approaches.
      Nanoparticles in the quantum regime have remarkable characteristics with
      excellent applicability in bioimaging. Yeasts have been commercially exploited
      for several industrial applications. ZnS nanoparticles as semiconductor quantum
      dots have mostly been synthesized by bacterial species. Here in, we have
      attempted to produce ZnS nanoparticles in quantum regime by Saccharomyces
      cerevisiae MTCC 2918 fungus and characterize its size and spectroscopic
      properties. Intracellular ZnS nanoparticles were produced by a facile procedure
      and freeze thaw extraction using 1mM zinc sulfate. The ZnS nanoparticles showed
      surface plasmon resonance band at 302.57nm. The ZnS nanoparticles were in low
      yield and in the size range of 30-40nm. Powder XRD analysis revealed that the
      nanoparticles were in the sphalerite phase. Photoluminescence spectra excited at
      280nm and 325nm revealed quantum confinement effects. This suggests that yeasts
      have inherent sulfate metabolizing systems and are capable fungal sources to
      assimilate sulfate. Further insights are required to identify the
      transport/reducing processes that may have caused the synthesis of ZnS
      nanoparticles such as an oxidoreductase enzyme-mediated mechanism. 

PMID- 24316440
TI  - The olive mill wastewater as substrate for single cell oil production by
      Zygomycetes.
AB  - The conversion of olive mill wastewater (OMW) into high added value lipids
      containing polyunsaturated fatty acids (PUFA), in parallel with a significant
      phenolic removal by selected strains of Zygomycetes, is reported here for the
      first time. The growth of Mortierella isabellina, Mortierella ramanniana,
      Cunninghamella echinulata, Mucor sp., Thamnidium elegans and Zygorhynchus
      moelleri on solidified media was not significantly affected by the presence of
      OMW used in the growth medium up to 50% (v/v). Kinetic parameter values and
      conversion yields, estimated using a mathematical model which was fitted on the
      experimental data originated from submerged cultures, shows the ability of some
      Zygomycetes (i.e. T. elegans and Z. moelleri) to grow on OMW and accumulate
      storage material, i.e. lipids rich in PUFA, and these findings open new
      perspectives in OMW management and valorization. In liquid media containing OMW
      as sole carbon source, T. elegans and Z. moelleri produced 4.4 and 3.5g/L cell
      mass in surface (SC) and submerged (SMC) cultures, respectively, containing
      around 60% (w/w) of lipids. Oleic and palmitic acids were the predominant fatty
      acids. Gamma-linolenic acid was found in high percentages (up to 17.7%, w/w) in
      the lipid of Z. moelleri, in SMC with OMW as sole carbon source, while PUFA
      biosynthesis was not favored in SC. 

PMID- 24316441
TI  - Curcumin promotes the spinal cord repair via inhibition of glial scar formation
      and inflammation.
AB  - Spinal cord injury (SCI) is a serious clinical situation without any effective
      therapy to date. Traumatic SCI triggers a complex pathological process including
      inflammatory response and glial scar formation. In this study, we demonstrated
      that curcumin, a natural product which functions as an anti-inflammatory agent,
      inhibited the activation of signal transducer and activator of transcription-3
      and NF-kappa B in the injured spinal cord. Curcumin treatment greatly reduced the
      astrogliosis in SCI mice and significantly decreased the expression of IL-1beta
      and NO, as well as the number of Iba1(+) inflammatory cells at the lesion site.
      Notably, more residual axons and neurons were protected and significantly
      improved functional recovery was observed in the curcumin-treated mice, compared
      to the mice without curcumin treatment. These findings indicate that curcumin
      promotes spinal cord repair through inhibiting glial scar formation and
      inflammation and suggests the therapeutic potential of curcumin for SCI. 

PMID- 24316443
TI  - The Monkey King: a personal view of the long journey towards a proteomic Nirvana.
AB  - The review covers about fifty years of progress in "proteome" analysis, starting
      from primitive two-dimensional (2D) map attempts in the early sixties of last
      century. The polar star in 2D mapping arose in 1975 with the classic paper by
      O'Farrell in J Biol. Chem. It became the compass for all proteome navigators.
      Perfection came, though, only with the introduction of immobilized pH gradients,
      which fixed the polypeptide spots in the 2D plane. Great impetus in proteome
      analysis came with the introduction of informatic tools and creating databases,
      among which Swiss Prot remains the site of excellence. Towards the end of the
      nineties, 2D chromatography, epitomized by coupling strong cation exchangers with
      C18 resins, began to be a serious challenge to electrophoretic 2D mapping,
      although up to the present both techniques are still much in vogue and appear to
      give complementary results. Yet the migration of "proteomics" into the third
      millennium was made possible only by mass spectrometry (MS), which today
      represents the standard analytical tool in any lab dealing with proteomic
      analysis. Another major improvement has been the introduction of combinatorial
      peptide ligand libraries (CPLL), which, when properly used, enhance the
      visibility of low-abundance species by 3 to 4 orders of magnitude. Coupling MS to
      CPLLs permits the exploration of at least 8 orders of magnitude in dynamic range
      on any proteome. BIOLOGICAL SIGNIFICANCE: The present review is a personal
      recollection highlighting the developments that led to present-day proteomics on
      a long march that lasted about 50years. It is meant to give to young scientists
      an overview on how science grows, which ones are the quantum jumps in science and
      which research is of particular significance in general and in the field of
      proteomics in particular. It also gives some real-life episodes of greater-than
      life figures. As such, it can be viewed as a tutorial to stimulate the young
      generation to be creative (and use their imagination too!).This article is part
      of a Special Issue entitled: 20years of Proteomics in memory of Viatliano
      Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis
      Hochstrasser and Jean-Charles Sanchez.

PMID- 24316442
TI  - 3D actin network centerline extraction with multiple active contours.
AB  - Fluorescence microscopy is frequently used to study two and three dimensional
      network structures formed by cytoskeletal polymer fibers such as actin filaments
      and actin cables. While these cytoskeletal structures are often dilute enough to
      allow imaging of individual filaments or bundles of them, quantitative analysis
      of these images is challenging. To facilitate quantitative, reproducible and
      objective analysis of the image data, we propose a semi-automated method to
      extract actin networks and retrieve their topology in 3D. Our method uses
      multiple Stretching Open Active Contours (SOACs) that are automatically
      initialized at image intensity ridges and then evolve along the centerlines of
      filaments in the network. SOACs can merge, stop at junctions, and reconfigure
      with others to allow smooth crossing at junctions of filaments. The proposed
      approach is generally applicable to images of curvilinear networks with low SNR.
      We demonstrate its potential by extracting the centerlines of synthetic meshwork
      images, actin networks in 2D Total Internal Reflection Fluorescence Microscopy
      images, and 3D actin cable meshworks of live fission yeast cells imaged by
      spinning disk confocal microscopy. Quantitative evaluation of the method using
      synthetic images shows that for images with SNR above 5.0, the average vertex
      error measured by the distance between our result and ground truth is 1 voxel,
      and the average Hausdorff distance is below 10 voxels. 

PMID- 24316444
TI  - Where it hurts: a systematic review of pain-location tools for children.

PMID- 24316445
TI  - The human papillomavirus family and its role in carcinogenesis.
AB  - Human papillomaviruses (HPVs) are a family of small double-stranded DNA viruses
      that have a tropism for the epithelia of the genital and upper respiratory tracts
      and for the skin. Approximately 150 HPV types have been discovered so far, which
      are classified into several genera based on their DNA sequence. Approximately 15
      high-risk mucosal HPV types are clearly associated with cervical cancer; HPV16
      and HPV18 are the most carcinogenic since they are responsible for approximately
      50% and 20% of all cervical cancers worldwide, respectively. It is now also clear
      that these viruses are linked to a subset of other genital cancers, as well as
      head and neck cancers. Due to their high level of carcinogenic activity, HPV16
      and HPV18 are the most studied HPV types so far. Biological studies have
      highlighted the key roles in cellular transformation of the products of two viral
      early genes, E6 and E7. Many of the mechanisms of E6 and E7 in subverting the
      regulation of fundamental cellular events have been fully characterized,
      contributing not only to our knowledge of how the oncogenic viruses promote
      cancer development but also to our understanding of basic cell biology. Despite
      HPV research resulting in extraordinary achievements in the last four decades,
      significantly improving the screening and prophylaxis of HPV-induced lesions,
      additional research is necessary to characterize the biology and epidemiology of
      the vast number of HPV types that have been poorly investigated so far, with a
      final aim of clarifying their potential roles in other human diseases. 

PMID- 24316446
TI  - Development of a reverse transcription quantitative real-time PCR-based system
      for rapid detection and quantitation of hepatitis delta virus in the western
      Amazon region of Brazil.
AB  - The hepatitis delta virus (HDV) is a pathogen that causes a severe and rapidly
      progressive disease of hepatocytes. The measurement of viral load in the
      peripheral blood of patients with HDV infections is important for diagnosis,
      treatment monitoring, and support for follow-up studies of viral replication
      during the course of the disease. This study reports the development of an assay
      capable of detecting and quantifying the abundance of HDV particles in serum
      samples, based on reverse-transcription quantitative PCR (RT-qPCR). Two standards
      for calibration were produced for determining the viral load of HDV: a cDNA
      cloned into a linear plasmid and a transcribed RNA. For validating this assay,
      140 clinical samples of sera were used, comprising 100 samples from patients who
      tested positive for anti-HDV and hepatitis B virus surface antigen (HBsAg) by
      ELISA; 30 samples from blood donors; 5 samples monoinfected with hepatitis B
      virus (HBV); and 5 samples monoinfected with hepatitis C virus (HCV). The HDV RT
      qPCR assay performed better when calibrated using the standard based on HDV cDNA
      cloned into a linear plasmid, yielding an efficiency of 99.8% and a specificity
      of 100% in the in vitro assays. This study represents the first HDV RT-qPCR assay
      developed with clinical samples from Brazil and offers great potential for new
      clinical efficacy studies of antiviral therapeutics for use in patients with
      hepatitis delta in the western Amazon region. 

PMID- 24316447
TI  - Cloning, overexpression and characterization of a thermostable pullulanase from
      Thermus thermophilus HB27.
AB  - A gene encoding a special type of pullulanase from Thermus thermophilus HB27
      (TTHpu) was cloned. It has an open reading frame of 1428bp encoding a mature
      protein with a molecular mass of 52kDa. The gene was expressed in Escherichia
      coli using pHsh and pET28a vectors. The pHsh expression system produced a 3.6
      fold higher recombinant pullulanase than pET28a. The recombinant TTHpu was
      purified to homogeneity by heat treatment and Ni-NTA affinity chromatography. The
      purified TTHpu exhibited highest activity at pH 6.5 and 70 degrees C. More than
      90% activity was retained after incubation at 60-70 degrees C for 2h and the half
      life was 2h at 80 degrees C. The stability of the enzyme was in a pH range from
      6.0 to 8.0. Manganese at 5mM enhanced its activity up to 298%. The Km and Vmax
      for the enzyme activity on pullulan were 0.0031mgmL(-1) and 23.8MUmolmin(-1),
      respectively. Unlike the most of pullulan-hydrolyzing enzymes described to date,
      this enzyme can attack alpha-1,6- and alpha-1,4-glycosidic linkages in pullulan,
      and produce a mixture of maltotriose, maltose and glucose. The enzyme could be
      further employed for industrial saccharification of starch. 

PMID- 24316448
TI  - The expression of vesicular glutamate transporter 3 and vesicular monoamine
      transporter 2 induced by brain-derived neurotrophic factor in dorsal root
      ganglion neurons in vitro.
AB  - The vesicular glutamate transporter 3 (VGLUT3) and the vesicular monoamine
      transporter 2 (VMAT2) are expressed in dorsal root ganglion (DRG) neurons and
      play an important role in packing the neurotransmitter into synaptic vesicles.
      Brain-derived neurotrophic factor (BDNF) is one of the most profound known
      regulators of survival in the developing peripheral nervous system (PNS). Whether
      BDNF regulates the expression of VGLUT3 and VMAT2 in DRG neurons is still
      unclear. In the present study, primary cultured rat DRG neurons were used to
      evaluate the effects of BDNF on VGLUT3 and VMAT2 expression. The signaling
      pathways of the extracellular signal-regulated protein kinase 1/2 (ERK1/2), the
      phosphatidylinositol 3-kinase (PI3K)/Akt, and the phospholipase C-gamma (PLC
      gamma) involved in these effects were also determined. DRG neurons at 48h post
      culture were incubated with BDNF and/or ERK1/2 inhibitor PD98059, PI3K inhibitor
      LY294002, and PLC-gamma inhibitor U73122 for an additional 24h. After that, the
      neurite growth and growth-associated protein 43 (GAP-43) expressions after
      different doses of BDNF treatment were determined by immunofluorescent labeling.
      The expression of mRNA and protein of VGLUT3 and VMAT2 in different experimental
      conditions was assessed by real-time PCR, immunoblotting, and immunofluorescent
      labeling, respectively. The results showed that BDNF exposure promoted neurite
      growth and GAP-43 expression in DRG neurons in a dose-dependent manner. BDNF
      induced VGLUT3 upregulation through activation of PLC-gamma signaling pathway.
      Although BDNF administration did not elevate the levels of VMAT2, the block of
      the PI3K/Akt or PLC-gamma signaling pathways could inhibit VMAT2 expression in
      DRG neurons in the presence of BDNF. The knockdown of VGLUT3 or VMAT2 gene by
      siRNA did not affect the BDNF's effects on GAP-43 upregulation and neurite
      growth. The upregulation of VGLUT3 induced by BDNF might be that BDNF improved
      neuronal outgrowth status by promoting GAP-43 expression to stimulate neurite
      elongation. The contribution of distinct VGLUT3 and VMAT2 transporter expression
      induced by BDNF might be one of the mechanisms that BDNF regulates neuropathic
      pain. These data imply that BDNF signaling system might be a potential target on
      modifying distinct transporter-mediated biological effects of primary sensory
      neurons. 

PMID- 24316449
TI  - Rapid detection of trace bacteria in biofluids using porous monoliths in
      microchannels.
AB  - We present advancements in microfluidic technology for rapid detection of as few
      as 10 rickettsial organisms in complex biological samples. An immuno-reactive
      filter, macroporous polyacrylamide monolith (PAM), fabricated within a
      microfluidic channel enhances solid-phase immuno-capture, staining and detection
      of targeted bacteria. Bacterial cells in samples flowing through the channel are
      forced to interact with the PAM filter surface due to size exclusion, overcoming
      common transport and kinetic limitations for rapid (min), high-efficiency (~100%)
      capture. In the process, targeted cells in sample volumes of 10 MUl to >100 MUl
      are concentrated within a sub-50 nl region at the PAM filter edge in the
      microchannel, thus concentrating them over 1000-fold. This significantly
      increases sensitivity, as the hydrophilic PAM also yields low non-specific immuno
      fluorescence backgrounds with samples including serum, blood and non-targeted
      bacteria. The concentrated target cells are detected using fluorescently-labeled
      antibodies. With a single 2.0*2.0*0.3 mm PAM filter, as few as 10 rickettsial
      organisms per 100 ul of lysed blood sample can be analyzed within 60 min, as
      compared to hours or even days needed for conventional detection methods. This
      method is highly relevant to rapid, multiplexed, low-cost point of care
      diagnostics at early stages of infection where diagnostics providing more
      immediate and actionable test results are needed to improve patient outcomes and
      mitigate potential natural and non-natural outbreaks or epidemics of rickettsial
      diseases.

PMID- 24316450
TI  - Micropallet arrays for the capture, isolation and culture of circulating tumor
      cells from whole blood of mice engrafted with primary human pancreatic
      adenocarcinoma.
AB  - Circulating tumor cells (CTCs) are important biomarkers of cancer progression and
      metastatic potential. The rarity of CTCs in peripheral blood has driven the
      development of technologies to isolate these tumor cells with high specificity;
      however, there are limited techniques available for isolating target CTCs
      following enumeration. A strategy is described to capture and isolate viable
      tumor cells from whole blood using an array of releasable microstructures termed
      micropallets. Specific capture of nucleated cells or cells expressing epithelial
      cell adhesion molecules (EpCAM) was achieved by functionalizing micropallet
      surfaces with either fibronectin, Matrigel or anti-EpCAM antibody. Surface
      grafting of poly(acrylic acid) followed by covalent binding of protein A/G
      enabled efficient capture of EpCAM antibody on the micropallet surface. MCF-7
      cells, a human breast adenocarcinoma, were retained on the array surface with
      90+/-8% efficiency when using an anti-EpCAM-coated array. To demonstrate the
      efficiency of tumor cell retention on micropallet arrays in the presence of
      blood, MCF-7 cells were mixed into whole blood and added to small arrays (71
      mm(2)) coated with fibronectin, Matrigel or anti-EpCAM. These approaches achieved
      MCF-7 cell capture from <=10 uL of whole blood with efficiencies greater than
      85%. Furthermore, MCF-7 cells intermixed with 1 mL blood and loaded onto large
      arrays (7171 mm(2)) were captured with high efficiencies (>=97%), could be
      isolated from the array by a laser-based approach and were demonstrated to yield
      a high rate of colony formation (>=85%) after removal from the array. Clinical
      utility of this technology was shown through the capture, isolation and
      successful culture of CTCs from the blood of mice engrafted with primary human
      pancreatic tumors. Direct capture and isolation of living tumor cells from blood
      followed by analysis or culture will be a valuable tool for cancer cell
      characterization.

PMID- 24316451
TI  - Microalgae dual-head biosensors for selective detection of herbicides with fiber
      optic luminescent O2 transduction.
AB  - The microalgal species Dictyosphaerium chlorelloides (D. c.) was immobilized into
      porous silicone films and their photosynthetic activity was monitored with an
      integrated robust luminescent O2 sensor. The biosensor specificity towards a
      particular pesticide has been achieved by manufacturing a fiber-optic dual-head
      device containing both analyte-sensitive and analyte-resistant D. c. strains. The
      latter are not genetically modified microalgae, but a product of modified Luria
      Delbruck fluctuation analysis followed by ratchet selection cycles. In this way
      the target herbicide decreases the O2 production of the analyte-sensitive
      immobilized strain without affecting the analyte-resistant population response;
      any other pollutant will lower the O2 production of both strains. The effect of
      the sample flow-rate, exposure time to the herbicide, biomass loading, biosensor
      film thickness, intensity of the actinic light, illumination cycle, and
      temperature on the biosensor response has been evaluated using waterborne
      simazine as test bench. The biosensing device is able to provide in situ
      measurements of the herbicide concentration every 180 min. The biosensor limit of
      detection for this herbicide was 12 MUg L(-1), with a working range of 50-800 MUg
      L(-1). The biosensor specificity to simazine has been assessed by comparing its
      response to that of isoproturon.

PMID- 24316452
TI  - A simple and portable device for the quantification of TNF-alpha in human plasma
      by means of on-chip magnetic bead-based proximity ligation assay.
AB  - There is a general need in healthcare systems all around the world to reduce
      costs in terms of time and money without compromising patients outcome. Point-of
      Care Testing (POCT) is currently being used in some applications (e.g. POC
      coagulation devices) as an alternative to already established standard central
      laboratory tests to overcome sample transportation and long turnaround times. The
      main objective of this investigation was to quantify Tumour Necrosis Factor-alpha
      (TNF-alpha) on-chip within the clinical relevant range of 5-100 pg/mL in human
      pooled plasma. The novel solid-phase assay developed in this study was a magnetic
      bead-based proximity ligation assay (PLA) in which one of the assay proximity
      probes was directly immobilised onto streptavidin-coated magnetic beads. The
      portable device was based on a disposable and single-use cyclo-olefin polymer
      (COP) microfluidic chip interfaced with a quantitative real-time polymerase chain
      reaction (qPCR) device previously developed in-house. Sample volume was 10 uL and
      total assay time under 3 h. The POC device and assay developed offer portability,
      smaller reagent and sample consumption, and faster time-to-results compared with
      standard ELISAs. Determination and monitoring of TNF-alpha therapy at the point
      of-care will help to improve clinical and/or economical outcome in governmental
      healthcare budgets.

PMID- 24316453
TI  - Low level drug product API form analysis - Avalide tablet NIR quantitative method
      development and robustness challenges.
AB  - Avalide(@), a medication used for the treatment of hypertension, is a combination
      of Irbesartan, and Hydrochlorothiazide. Irbesartan, one of the active
      pharmaceutical ingredients (API) in Avalide products, exists in two neat
      crystalline forms: Form A and Form B. Irbesartan Form A is the API form used in a
      wet granulation for the preparation of Avalide tablets. The presence of the less
      soluble Irbesartan Form B in Avalide tablets may result in the slower
      dissolution. In this paper, we have presented our work on the method development,
      verification and challenges of quantitatively detecting, via NIR and ssNMR, very
      small amounts of Irbesartan Form B in Avalide tablets. As part of the NIR method
      development and qualification, limit of detection, linearity and accuracy were
      examined. In addition, a limited study of the robustness of the method was
      conducted and a bias in the level of Form B was correlated to the ambient
      humidity. ssNMR, a primary method for the determination of polymorphic
      composition, was successfully used as an orthogonal technique to verify the
      accuracy of the NIR method and added to the confidence in the NIR method. The
      speed and efficiency of the NIR method make it a suitable and convenient tool for
      routine analysis of Avalide tablets for Form B in a QC environment. 

PMID- 24316455
TI  - Reducing barriers to nursing certification: an analysis of perceptions and impact
      of PNCB's No Pass, No Pay Program.
AB  - The number of board-certified RNs in the United States continues to increase, but
      cost and fear of failure inhibit many from seeking certification. In 2009, the
      Pediatric Nursing Certification Board developed a no-risk program called No Pass,
      No Pay (NPNP) for its Certified Pediatric Nurse (CPN(r)) exam. In 2012, 49% of
      the 2299 nurses earning CPN certification did so through NPNP. This article
      explores program structure, successes, and findings from 2011 stakeholder surveys
      of NPNP hospital leaders, NPNP program facilitators, and nurses who attained CPN
      certification through NPNP. Aspects of NPNP may prove applicable to other
      certification boards. 

PMID- 24316456
TI  - Nurses' labour supply elasticities: the importance of accounting for extensive
      margins.
AB  - We estimate a multi-sector model of nursing qualification holders' labour supply
      in different occupations. A structural approach allows us to model the labour
      force participation decision, the occupational and shift-type choice, and the
      decision about hours worked as a joint outcome following from maximising a
      utility function. Disutility from work is allowed to vary by occupation and also
      by shift type in the utility function. Our results suggest that average wage
      elasticities might be higher than previous research has found. This is mainly due
      to the effect of wages on the decision to enter or exit the profession, which was
      not included in the previous literature, rather than from its effect on increased
      working hours for those who already work in the profession. 

PMID- 24316454
TI  - Defining the blanks--pharmacochaperoning of SLC6 transporters and ABC
      transporters.
AB  - SLC6 family members and ABC transporters represent two extremes: SLC6
      transporters are confined to the membrane proper and only expose small segments
      to the hydrophilic milieu. In ABC transporters the hydrophobic core is connected
      to a large intracellular (eponymous) ATP binding domain that is comprised of two
      discontiguous repeats. Accordingly, their folding problem is fundamentally
      different. This can be gauged from mutations that impair the folding of the
      encoded protein and give rise to clinically relevant disease phenotypes: in SLC6
      transporters, these cluster at the protein-lipid interface on the membrane
      exposed surface. Mutations in ABC-transporters map to the interface between
      nucleotide binding domains and the coupling helices, which provide the connection
      to the hydrophobic core. Folding of these mutated ABC-transporters can be
      corrected with ligands/substrates that bind to the hydrophobic core. This
      highlights a pivotal role of the coupling helices in the folding trajectory. In
      contrast, insights into pharmacochaperoning of SLC6 transporters are limited to
      monoamine transporters - in particular the serotonin transporter (SERT) - because
      of their rich pharmacology. Only ligands that stabilize the inward facing
      conformation act as effective pharmacochaperones. This indicates that the folding
      trajectory of SERT proceeds via the inward facing conformation. Mutations that
      impair folding of SLC6 family members can be transmitted as dominant or recessive
      alleles. The dominant phenotype of the mutation can be rationalized, because SLC6
      transporters are exported in oligomeric form from the endoplasmic reticulum (ER).
      Recessive transmission requires shielding of the unaffected gene product from the
      mutated transporter in the ER. This can be accounted for by a chaperone-COPII
      (coatomer protein II) exchange model, where proteinaceous ER-resident chaperones
      engage various intermediates prior to formation of the oligomeric state and
      subsequent export from the ER. It is likely that the action of pharmacochaperones
      is contingent on and modulated by these chaperones. 

PMID- 24316457
TI  - A mass phenomenon: the social evolution of obesity.
AB  - This paper proposes a theory for the social evolution of obesity. It considers a
      society in which individuals experience utility from consumption of food and non
      food, the state of their health, and the evaluation of their appearance by
      others. The theory explains under which conditions poor persons are more prone to
      be overweight although eating is expensive and it shows how obesity occurs as a
      social phenomenon such that body mass continues to rise long after the initial
      cause (e.g. a lower price of food) is gone. The paper investigates the
      determinants of a steady state at which the median person is overweight and how
      an originally lean society arrives at such a steady state. Extensions of the
      theory towards dietary choice and the possibility to exercise in order to lose
      weight demonstrate robustness of the basic mechanism and provide further
      interesting results. 

PMID- 24316458
TI  - Peer effects on risky behaviors: new evidence from college roommate assignments.
AB  - Social scientists continue to devote considerable attention to spillover effects
      for risky behaviors because of the important policy implications and the
      persistent challenges in identifying unbiased causal effects. We use the natural
      experiment of assigned college roommates to estimate peer effects for several
      measures of health risks: binge drinking, smoking, illicit drug use, gambling,
      having multiple sex partners, suicidal ideation, and non-suicidal self-injury. We
      find significant peer effects for binge drinking but little evidence of effects
      for other outcomes, although there is tentative evidence that peer effects for
      smoking may be positive among men and negative among women. In contrast to prior
      research, the peer effects for binge drinking are significant for all subgroups
      defined by sex and prior drinking status. We also find that pre-existing risky
      behaviors predict the closeness of friendships, which underscores the
      significance of addressing selection biases in studies of peer effects. 

PMID- 24316459
TI  - Cytokine and chemokine patterns across 100 days after hematopoietic stem cell
      transplantation in children.
AB  - We mapped the cytokine response to hematopoietic stem cell transplantation (HSCT)
      by assaying 51 cytokines and chemokines each week for 100 days in 51 children
      receiving allogeneic (n = 44) or autologous HSCT (n = 7). Assay values were
      reported as mean fluorescence intensity (MFI). Log transformation converted MFI
      to clinically relevant measures (ie, pg/mL). We searched for potential markers of
      transplant complications by using mixed treatment by subject analysis of
      variance. Global cytokine secretion in HSCT recipients was significantly lower
      than in concurrent control patients (n = 11). Coincident with the nadir in WBC
      count, the concentration of many cytokines declined further by the second and
      third week. All analytes (except monokine induced by gamma interferon [MIG])
      subsequently rebounded by week 4 (coincident with engraftment and recovery of WBC
      count) but often still remained well below control levels. Concurrent with the
      collective nadir of multiple cytokines, monocyte chemoattractant protein 1 (MCP
      1), growth-regulated oncogene alpha (GRO-a), and leptin surged during weeks 2 to
      4. High levels of leptin persisted throughout the 100 post-transplant days. Also
      during weeks 2 to 4, hepatocyte growth factor (HGF) and IL-6 surged in children
      with complications but not in those without complications. The peak in HGF was
      more pronounced in veno-occlusive disease (VOD). HGF and IL-6 secretion rose at
      least 2 weeks before the clinical diagnosis of VOD or graft-versus-host disease
      (GVHD). From week 4 onward in all groups, the MFI of the cytokine resistin
      increased to 5 to 15 times above concurrent control. HGF has now emerged in 3 or
      more biomarker discovery efforts for GVHD (and in our population for VOD as
      well). HGF (with or without IL-6) should be investigated as a potential
      predictive biomarker of VOD or GVHD. Alternatively, the hyperinflammatory
      "signature" provided by a multicytokine assay may be predictive.

PMID- 24316460
TI  - Hematopoietic stem cell transplantation in children and young adults with
      secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic
      anemia.
AB  - Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are
      the most serious secondary events occurring after immunosuppressive therapy in
      patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem
      cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after
      childhood aplastic anemia. The median interval between the diagnosis of aplastic
      anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years).
      At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT
      with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA
      matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated
      donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen
      consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other
      agents in 6 patients. All patients achieved neutrophil engraftment. The
      cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was
      47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major
      cause of death was transplant-related complication (n = 9). Overall survival and
      event-free survival at 5 years after HSCT were both 41%. In summary, this study
      indicates that HSCT is a curative therapy for some patients with sMDS/sAML after
      aplastic anemia. Future efforts should focus on reducing transplantation-related
      mortality.

PMID- 24316461
TI  - Paracetamol impairs the profile of amino acids in the rat brain.
AB  - In our experiment we investigated the effect of subcutaneous administration of
      paracetamol on the levels of amino acids in the brain structures. Male Wistar
      rats received for eight weeks paracetamol at two doses: 10 mg/kg b.w. (group P10,
      n=9) and 50 mg/kg b.w. per day s.c. (group P50, n=9). The regional brain
      concentrations of amino acids were determined in the prefrontal cortex,
      hippocampus, hypothalamus and striatum of control (Con, n=9) and paracetamol
      treated groups using HPLC. Evaluation of the biochemical results indicated
      considerable decrease of the content of amino acids in the striatum (glutamine,
      glutamic acid, taurine, alanine, aspartic acid) and hypothalamus (glycine)
      between groups treated with paracetamol compared to the control. In the
      prefrontal cortex paracetamol increased the level of gamma-aminobutyric acid
      (GABA). The present study demonstrated significant effect of the long term
      paracetamol treatment on the level of amino acids in the striatum, prefrontal
      cortex and hypothalamus of rats.

PMID- 24316462
TI  - Leishmania amazonensis: characterization of an ecto-pyrophosphatase activity.
AB  - Several ecto-enzymatic activities have been described in the plasma membrane of
      the protozoan Leishmania amazonensis, which is the major etiological agent of
      diffuse cutaneous leishmaniasis in South America. These enzymes, including ecto
      phosphatases, contribute to the survival of the parasite by participating in
      phosphate metabolism. This work identifies and characterizes the extracellular
      hydrolysis of inorganic pyrophosphate related to an ecto-pyrophosphatase activity
      of the promastigote form of L. amazonensis. This ecto-pyrophosphatase activity is
      insensitive to MnCl2 but is strongly stimulated by MgCl2. This stimulation was
      not observed during the hydrolysis of p-nitrophenyl phosphate (p-NPP) or beta
      glycerophosphate, two substrates for different ecto-phosphatases present in the
      L. amazonensis plasma membrane. Furthermore, extracellular PPi hydrolysis is more
      efficient at alkaline pHs, while p-NPP hydrolysis occurs mainly at acidic pHs.
      These results led us to conclude that extracellular PPi is hydrolyzed not by non
      specific ecto-phosphatases but rather by a genuine ecto-pyrophosphatase. In the
      presence of 5mM MgCl2, the ecto-pyrophosphatase activity from L. amazonensis is
      sensitive to micromolar concentrations of NaF and millimolar concentrations of
      CaCl2. Moreover, this activity is significantly higher during the first days of
      L. amazonensis culture, which suggests a possible role for this enzyme in
      parasite growth. 

PMID- 24316463
TI  - An integrated microfludic device for culturing and screening of Giardia lamblia.
AB  - In vitro culturing of trophozoites was important for research of Giardia lamblia
      (G. lamblia), especially in discovery of anti-Giardia agents. The current culture
      methods mainly suffer from lab-intension or the obstacle in standardizing the gas
      condition. Thus, it could benefit from a more streamlined and integrated
      approach. Microfluidics offers a way to accomplish this goal. Here we presented
      an integrated microfluidic device for culturing and screening of G. lamblia. The
      device consisted of a polydimethylsiloxane (PDMS) microchip with an aerobic
      culture system. In the microchip, the functionality of integrated concentration
      gradient generator (CGG) with micro-scale cell culture enables dose-response
      experiment to be performed in a simple and reagent-saving way. The diffusion
      based culture chambers allowed growing G. lamblia at the in vivo like
      environment. It notable that the highly air permeable material of parallel
      chambers maintain uniform anaerobic environment in different chambers easily.
      Using this device, G. lamblia were successfully cultured and stressed on-chip. In
      all cases, a dose-related inhibitory response was detected. The application of
      this device for these purposes represents the first step in developing a
      completely integrated microfluidic platform for high-throughput screening and
      might be expanded to other assays based on in vitro culture of G. lamblia with
      further tests. 

PMID- 24316464
TI  - Infection of small ruminants and their red blood cells with Theileria annulata
      schizonts.
AB  - Theileria annulata, the causative agent of tropical theileriosis, is a protozoan
      parasite that also causes lymphoproliferative diseases in cattle. In vivo,
      parasitized cells undergo clonal expansion and infiltrate both the lymphoid and
      non-lymphoid tissues of the infected host. To determine whether the small
      ruminants and their red blood cells (RBCs) were invaded by T. annulata schizonts
      or not, T. annulata schizonts were used to infect bovine, ovine and caprine RBCs
      in vitro, and sheep and goats in vivo. The results showed that the schizonts
      infected bovine, ovine and caprine RBCs in vitro, but not sheep and goats, which
      showed only an increase in body temperature and no development of piroplasms. To
      our knowledge, this is the first report of infection of small ruminants and their
      RBCs by T. annulata schizonts. 

PMID- 24316466
TI  - In vitro and in vivo characterization of the agonist-dependent D3 dopamine
      receptor tolerance property.
AB  - The D3 dopamine receptor has the highest affinity for dopamine, many
      antipsychotics as well as agonists used to treat Parkinson's disease and related
      disorders. We and others have reported that the D3 receptor exhibits a tolerance
      property wherein repeated agonist stimulation of the receptor results in a
      progressive loss of agonist-induced signaling response. Recently we reported that
      the D3 receptor tolerance property is agonist dependent and identified a novel
      agonist, ES609, which does not elicit D3 receptor tolerance. Here, we used the
      classical tolerance-inducing D3 receptor agonist, PD128907, and the novel
      agonist, ES609, to demonstrate that the D3 receptor tolerance property is
      exhibited not only in cellular signaling in vitro and in vivo, but also manifests
      at the behavior level. Using AtT-20 cells stably expressing D3 receptors we show
      that PD128907, but not ES609, induces tolerance in the D3 receptor-mitogen
      activated protein kinase (MAPK) pathway. Using the novel drd3-EGFP reporter mice,
      we demonstrate that 0.05 mg/kg PD128907 and 10 mg/kg ES609 selectively activate
      the D3 receptor-MAPK signaling pathway in vivo; however, only PD128907 induces
      tolerance. Locomotor behavior assessment showed that both PD128907 and ES609
      decreased locomotor activity of the drd3-EGFP mice. While the agonist-induced
      decrease in locomotor activity was attenuated in drd3-EGFP mice administered two
      sequential doses of tolerance-inducing agonist PD128907, this attenuation was not
      seen in mice repeatedly administered the novel agonist, ES609. Together the
      results suggest that the D3 receptor tolerance property is exhibited in MAPK
      signaling in vitro and in vivo and also affects agonist-induced locomotor
      behavior. 

PMID- 24316467
TI  - A network of players in H3 histone variant deposition and maintenance at
      centromeres.
AB  - Centromeres are key chromosomal landmarks important for chromosome segregation
      and are characterized by distinct chromatin features. The centromeric histone H3
      variant, referred to as CENP-A or CenH3(CENP-A) in mammals, has emerged as a key
      determinant for centromeric structure, function and epigenetic inheritance. To
      regulate the correct incorporation and maintenance of histones at this locus, the
      cell employs an intricate network of molecular players, among which histone
      chaperones and chromatin remodelling factors have been identified over the past
      years. The mammalian centromere-specific chaperone HJURP represents an
      interesting paradigm to understand the functioning of this network. This review
      highlights and discusses the latest findings on centromeric histone H3 variant
      deposition and regulation to delineate the current view on centromere
      establishment, maintenance and propagation throughout the cell cycle. This
      article is part of a Special Issue entitled: Chromatin and epigenetic regulation
      of animal development. 

PMID- 24316465
TI  - Telmisartan ameliorates glutamate-induced neurotoxicity: roles of AT(1) receptor
      blockade and PPARgamma activation.
AB  - Sartans (Angiotensin II AT(1) Receptor Blockers, ARBs) are powerful
      neuroprotective agents in vivo and protect against IL-1beta neurotoxicity in
      vitro. The purpose of this research was to determine the extent of sartan
      neuroprotection against glutamate excitotoxicity, a common cause of neuronal
      injury and apoptosis. The results show that sartans are neuroprotective,
      significantly reducing glutamate-induced neuronal injury and apoptosis in
      cultured rat primary cerebellar granule cells (CGCs). Telmisartan was the most
      potent sartan studied, with an order of potency telmisartan > candesartan >
      losartan > valsartan. Mechanisms involved reduction of pro-apoptotic caspase-3
      activation, protection of the survival PI3K/Akt/GSK-3beta pathway and prevention
      of glutamate-induced ERK1/2 activation. NMDA receptor stimulation was essential
      for glutamate-induced cell injury and apoptosis. Participation of AT(1A) receptor
      was supported by glutamate-induced upregulation of AT(1A) gene expression and
      AT(1) receptor binding. Conversely, AT(1B) or AT(2) receptors played no role.
      Glutamate-induced neuronal injury and the neuroprotective effect of telmisartan
      were decreased, but not abolished, in CGCs obtained from AT(1A) knock-out mice.
      This indicates that although AT(1) receptors are necessary for glutamate to exert
      its full neurotoxic potential, part of the neuroprotective effect of telmisartan
      is independent of AT(1) receptor blockade. PPARgamma activation was also involved
      in the neuroprotective effects of telmisartan, as telmisartan enhanced PPARgamma
      nuclear translocation and the PPARgamma antagonist GW9662 partially reversed the
      neuroprotective effects of telmisartan. The present results substantiate the
      therapeutic use of sartans, in particular telmisartan, in neurodegenerative
      diseases and traumatic brain disorders where glutamate neurotoxicity plays a
      significant role.

PMID- 24316468
TI  - Possible crosstalk between leptin and prolactin during pregnancy.
AB  - Rodents exhibit leptin resistance and high levels of prolactin/placental
      lactogens during pregnancy. A crosstalk between prolactin and leptin signaling
      has been proposed as a possible mechanism to explain the changes in energy
      balance during gestation. However, it remains unclear if specific neuronal
      populations co-express leptin and prolactin receptors. Therefore, our present
      study was undertaken to identify in the mouse brain prolactin-responsive cells
      that possibly express the leptin receptor (LepR). In addition, we assessed the
      leptin response in different brain nuclei of pregnant and nulliparous mice. We
      used a LepR-reporter mouse to visualize LepR-expressing cells with the tdTomato
      fluorescent protein. Prolactin-responsive cells were visualized with the
      immunohistochemical detection of the phosphorylated form of the signal transducer
      and activator of transcription-5 (pSTAT5-ir). Notably, many neurons that co
      expressed tdTomato and pSTAT5-ir were observed in the medial preoptic area (MPA,
      27-48% of tdTomato cells), the retrochiasmatic area (34-51%) and the nucleus of
      the solitary tract (NTS, 16-24%) of prolactin-treated nulliparous mice, pregnant
      mice and prolactin-treated leptin-deficient (ob/ob) mice. The arcuate nucleus of
      the hypothalamus (8-22%), the medial tuberal nucleus (11-15%) and the ventral
      premammillary nucleus (4-10%) showed smaller percentages of double-labeled cells
      among the groups. Other brain nuclei did not show significant percentages of
      neurons that co-expressed tdTomato and pSTAT5-ir. Late pregnant mice exhibited a
      reduced leptin response in the MPA and NTS when compared with nulliparous mice;
      however, a normal leptin response was observed in other brain nuclei. In
      conclusion, our findings shed light on how the brain integrates the information
      conveyed by leptin and prolactin. Our results corroborate the hypothesis that
      high levels of prolactin or placental lactogens during pregnancy may directly
      interfere with LepR signaling, possibly predisposing to leptin resistance. 

PMID- 24316469
TI  - The chemokine CCL5 induces CCR1-mediated hyperalgesia in mice inoculated with
      NCTC 2472 tumoral cells.
AB  - Although the expression of the chemokine receptor CCR1 has been demonstrated in
      several structures related to nociception, supporting the nociceptive role of
      chemokines able to activate it, the involvement of CCR1 in neoplastic pain has
      not been previously assessed. We have assayed the effects of a CCR1 antagonist,
      J113863, in two murine models of neoplastic hyperalgesia based on the intratibial
      injection of either NCTC 2472 fibrosarcoma cells, able to induce osteolytic bone
      injury, or B16-F10 melanoma cells, associated to mixed osteolytic/osteoblastic
      bone pathological features. The systemic administration of J113863 inhibited
      thermal and mechanical hyperalgesia but not mechanical allodynia in mice
      inoculated with NCTC 2472 cells. Moreover, in these mice, thermal hyperalgesia
      was counteracted following the peritumoral (10-30MUg) but not spinal (3-5MUg)
      administration of J113863. In contrast, hyperalgesia and allodynia measured in
      mice inoculated with B16-F10 cells remained unaffected after the administration
      of J113863. The inoculation of tumoral cells did not modify the levels of CCL3 at
      tumor or spinal cord. In contrast, although the concentration of CCL5 remained
      unmodified in mice inoculated with B16-F10 cells, increased levels of this
      chemokine were measured in tumor-bearing limbs, but not the spinal cord, of mice
      inoculated with NCTC 2472 cells. Increased levels of CCL5 were also found
      following the incubation of NCTC 2472, but not B16-F10, cells in the
      corresponding culture medium. The intraplantar injection of CCL5 (0.5ng) to naive
      mice evoked thermal hyperalgesia prevented by the coadministration of J113863 or
      the CCR5 antagonist, d-Ala-peptide T-amide (DAPTA), demonstrating that CCL5 can
      induce thermal hyperalgesia in mice through the activation of CCR1 or CCR5.
      However, contrasting with the inhibitory effect evoked by J113863, the systemic
      administration of DAPTA did not prevent tumoral hyperalgesia. Finally, the
      peritumoral administration of an anti-CCL5 antibody completely inhibited thermal
      hyperalgesia evoked by the inoculation of NCTC 2472 cells. 

PMID- 24316471
TI  - Omega-3 prevents behavior response and brain oxidative damage in the ketamine
      model of schizophrenia.
AB  - Supplementation with omega-3 has been identified as an adjunctive alternative for
      the treatment of psychiatric disorders, in order to minimize symptoms.
      Considering the lack of understanding concerning the pathophysiology of
      schizophrenia, the present study hypothesized that omega 3 prevents the onset of
      symptoms similar to schizophrenia in young Wistar rats submitted to ketamine
      treatment. Moreover, the role of oxidative stress in this model was assessed.
      Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both
      treatments were performed during 21days, starting at the 30th day of life in
      young rats. After 14days of treatment with omega-3 or vehicle, a concomitant
      treatment with saline or ketamine (25mg/kg ip daily) was started and maintained
      until the last day of the experiment. We evaluated the pre-pulse inhibition of
      the startle reflex, activity of antioxidant systems and damage to proteins and
      lipids. Our results demonstrate that supplementation of omega-3 prevented:
      decreased inhibition of startle reflex, damage to lipids in the hippocampus and
      striatum and damage to proteins in the prefrontal cortex. Furthermore, these
      changes are associated with decreased GPx in brain tissues evaluated. Together,
      our results suggest the prophylactic role of omega-3 against the outcome of
      symptoms associated with schizophrenia. 

PMID- 24316472
TI  - Olfactory experience modulates immature neuron development in postnatal and adult
      guinea pig piriform cortex.
AB  - Immature neurons expressing doublecortin (DCX+) are present around cortical layer
      II in various mammals including guinea pigs and humans, especially enriched in
      the paleocortex. However, little is known whether and how functional experience
      affects the development of this population of neurons. We attempted to explore a
      modulation by experience to layer II DCX+ cells in the primary olfactory cortex
      in postnatal and adult guinea pigs. Neonatal and 1-year-old guinea pigs were
      subjected to unilateral naris-occlusion, followed 1 and 2months later by
      morphometry of DCX+ cells in the piriform cortex. DCX+ somata and processes were
      reduced in the deprived relative to the non-deprived piriform cortex in both age
      groups at the two surviving time points. The number of DCX+ cells was decreased
      in the deprived side relative to internal control at 1 and 2months in the youths
      and at 2months in the adults post-occlusion. The mean somal area of DCX+ cells
      showed a trend of decrease in the deprived side relative to the internal control
      in the youths. In addition, DCX+ cells in the deprived side exhibited a lower
      frequency of colocalization with the neuron-specific nuclear antigen (NeuN)
      relative to counterparts. These results suggest that normal olfactory experience
      is required for the maintenance and development of DCX+ immature neurons in
      postnatal and adult guinea pig piriform cortex. 

PMID- 24316470
TI  - Impact of hippocampal neuronal ablation on neurogenesis and cognition in the aged
      brain.
AB  - Neuronal loss is the most common and critical feature of a spectrum of brain
      traumas and neurodegenerative disorders such as Alzheimer's disease (AD). The
      capacity to generate new neurons in the central nervous system diminishes early
      during brain development and is restricted mainly to two brain areas in the
      mature brain: subventricular zone and subgranular zone. Extensive research on the
      impact of brain injury on endogenous neurogenesis and cognition has been
      conducted primarily using young animals, when neurogenesis is most active.
      However, a critical question remains to elucidate the effect of brain injury on
      endogenous neurogenesis and cognition in older animals, which is far more
      relevant for age-related neurodegenerative disorders such as AD. Therefore, we
      examined the impact of neuronal loss on endogenous neurogenesis in aged animals
      using CaM/Tet-DTA mice, a transgenic model of hippocampal cell loss.
      Additionally, we investigated whether the upregulation of adult neurogenesis
      could mitigate cognitive deficits following substantial hippocampal neuronal
      loss. Our findings demonstrate that aged CaM/Tet-DTA mice that sustain severe
      neuronal loss exhibit an upregulation of endogenous neurogenesis. However,
      despite this significant upregulation, neurogenesis alone is not able to mitigate
      the cognitive deficits observed. Our studies suggest that the aged brain has the
      capacity to stimulate neurogenesis post-injury; however, multiple therapeutic
      approaches, including upregulation of endogenous neurogenesis, will be necessary
      to recover brain function after severe neurodegeneration. 

PMID- 24316473
TI  - Treatment effects in a transgenic mouse model of Alzheimer's disease: a magnetic
      resonance spectroscopy study after passive immunization.
AB  - Despite the enormous public health impact of Alzheimer's disease (AD), no disease
      modifying treatment has yet been proven to be efficacious in humans. A rate
      limiting step in the discovery of potential therapies for humans is the absence
      of efficient non-invasive methods of evaluating drugs in animal models of
      disease. Magnetic resonance spectroscopy (MRS) provides a non-invasive way to
      evaluate the animals at baseline, at the end of treatment, and serially to better
      understand treatment effects. In this study, MRS was assessed as potential
      outcome measure for detecting disease modification in a transgenic mouse model of
      AD. Passive immunization with two different antibodies, which have been
      previously shown to reduce plaque accumulation in transgenic AD mice, was used as
      intervention. Treatment effects were detected by MRS, and the most striking
      finding was attenuation of myo-inositol (mIns) increases in APP-PS1 mice with
      both treatments. Additionally, a dose-dependent effect was observed with one of
      the treatments for mIns. MRS appears to be a valid in vivo measure of anti-Abeta
      therapeutic efficacy in pre-clinical studies. Because it is noninvasive, and can
      detect treatment effects, use of MRS-based endpoints could substantially
      accelerate drug discovery. 

PMID- 24316474
TI  - Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced
      Parkinson model mice.
AB  - Nobiletin, a polymethoxylated flavonoid found in citrus fruit peel, reportedly
      improves memory impairment in rodent models. Here we report its effect on 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor and cognitive
      deficits. Nobiletin administration (50mg/kg i.p.) for 2 consecutive weeks
      improved motor deficits seen in MPTP-induced Parkinson model mice by 2weeks, an
      effect that continued until 2weeks after drug withdrawal. Drug treatment promoted
      similar rescue of MPTP-induced cognitive impairment at equivalent time points.
      Nonetheless, nobiletin treatment did not block loss of dopaminergic neurons seen
      in the MPTP-treated mouse midbrain, nor did it rescue decreased tyrosine
      hydroxylase (TH) protein levels seen in the striatum or hippocampal CA1 region of
      these mice. Interestingly, nobiletin administration (50mg/kg i.p.) rescued
      reduced levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      autophosphorylation and phosphorylation at Thr-34 of dopamine- and cAMP-regulated
      phosphoprotein-32 (DARPP-32) in striatum and hippocampal CA1 to levels seen in
      sham-operated mice. Likewise, CaMKII- and cAMP kinase-dependent TH
      phosphorylation was significantly restored by nobiletin treatment. MPTP-induced
      reduction of dopamine contents in the striatum and hippocampal CA1 region was
      improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal
      administration of nobiletin also enhanced dopamine release in striatum and
      hippocampal CA1, an effect partially inhibited by treatment with nifedipine (a L
      type Ca(2+) channel inhibitor) or NNC 55-0396 (a T-type Ca(2+) channel inhibitor)
      and completely abolished by combined treatment with both. Overall, our study
      describes a novel nobiletin activity in brain and suggests that nobiletin rescues
      motor and cognitive dysfunction in MPTP-induced Parkinson model mice, in part by
      enhancing dopamine release. 

PMID- 24316476
TI  - Insight on the fate of CNS-targeted nanoparticles. Part I: Rab5-dependent cell
      specific uptake and distribution.
AB  - Nanocarriers can be useful tools for delivering drugs to the central nervous
      system (CNS). Their distribution within the brain and their interaction with CNS
      cells must be assessed accurately before they can be proposed for therapeutic
      use. In this paper, we investigated these issues by employing poly-lactide-co
      glycolide nanoparticles (NPs) specifically engineered with a glycopeptide (g7)
      conferring to NPs the ability to cross the blood brain barrier (BBB) at a
      concentration of up to 10% of the injected dose. g7-NPs display increased in
      vitro uptake in neurons and glial cells. Our results show that in vivo
      administration of g7-NPs leads to a region- and cell type-specific enrichment of
      NPs within the brain. We provide evidence that g7-NPs are endocytosed in a
      clathrin-dependent manner and transported into a specific subset of early
      endosomes positive for Rab5 in vitro and in vivo. The differential Rab5
      expression level is strictly correlated with the amount of g7-NP accumulation.
      These findings show that g7-NPs can cross the BBB and target specific brain cell
      populations, suggesting that these NPs can be promising carriers for the
      treatment of neuropsychiatric and neurodegenerative diseases. 

PMID- 24316475
TI  - GABAergic influence on temporomandibular joint-responsive spinomedullary neurons
      depends on estrogen status.
AB  - Sensory input from the temporomandibular joint (TMJ) to neurons in superficial
      laminae at the spinomedullary (Vc/C1-2) region is strongly influenced by estrogen
      status. This study determined if GABAergic mechanisms play a role in estrogen
      modulation of TMJ nociceptive processing in ovariectomized female rats treated
      with high- (HE) or low-dose (LE) estradiol (E2) for 2days. Superficial laminae
      neurons were activated by ATP (1mM) injections into the joint space. The
      selective GABAA receptor antagonist, bicuculline methiodide (BMI, 5 or 50MUM,
      30MUl), applied at the site of recording greatly enhanced the magnitude and
      duration of ATP-evoked responses in LE rats, but not in units from HE rats. The
      convergent cutaneous receptive field (RF) area of TMJ neurons was enlarged after
      BMI in LE but not HE rats, while resting discharge rates were increased after BMI
      independent of estrogen status. By contrast, the selective GABAA receptor
      agonist, muscimol (50MUM, 30MUl), significantly reduced the magnitude and
      duration of ATP-evoked activity, resting discharge rate, and cutaneous RF area of
      TMJ neurons in LE and HE rats, whereas lower doses (5MUM) affected only units
      from LE rats. Protein levels of GABAA receptor beta3 isoform at the Vc/C1-2
      region were similar for HE and LE rats. These results suggest that GABAergic
      mechanisms contribute significantly to background discharge rates and TMJ-evoked
      input to superficial laminae neurons at the Vc/C1-2 region. Estrogen status may
      gate the magnitude of GABAergic influence on TMJ neurons at the earliest stages
      of nociceptive processing at the spinomedullary region. 

PMID- 24316479
TI  - Pretreatment of corn stover for sugar production using dilute hydrochloric acid
      followed by lime.
AB  - In this study, a two stage process was evaluated to increase the sugar recovery.
      Firstly, corn stover was treated with diluted hydrochloric acid to maximize the
      xylose yield, and then the residue was treated with lime to alter the lignin
      structure and swell the cellulose surface. The optimal condition was 120  degrees
      C and 40 min for diluted hydrochloric acid pretreatment followed by lime
      pretreatment at 60  degrees C for 12h with lime loading at 0.1 g/g of substrate.
      The glucose and xylose yield was 78.0% and 97.0%, respectively, with cellulase
      dosage at 5 FPU/g of substrate. The total glucose yield increased to 85.9% when
      the cellulase loading was increased to 10 FPU/g of substrate. This two stage
      process was effective due to the swelling of the internal surface, an increase in
      the porosity and a decrease in the degree of polymerization.

PMID- 24316480
TI  - Relationship of trehalose accumulation with ethanol fermentation in industrial
      Saccharomyces cerevisiae yeast strains.
AB  - The protective effect and the mechanisms of trehalose accumulation in industrial
      Saccharomyces cerevisiae strains were investigated during ethanol fermentation.
      The engineered strains with more intercellular trehalose achieved significantly
      higher fermentation rates and ethanol yields than their wild strain ZS during
      very high gravity (VHG) fermentation, while their performances were not different
      during regular fermentation. The VHG fermentation performances of these strains
      were consistent with their growth capacity under osmotic stress and ethanol
      stress, the key stress factors during VHG fermentation. These results suggest
      that trehalose accumulation is more important for VHG fermentation of industrial
      yeast strains than regular one. The differences in membrane integrity and
      antioxidative capacity of these strains indicated the possible mechanisms of
      trehalose as a protectant under VHG condition. Therefore, trehalose metabolic
      engineering may be a useful strategy for improving the VHG fermentation
      performance of industrial yeast strains. 

PMID- 24316481
TI  - Dual substrate strategy to enhance butanol production using high cell inoculum
      and its efficient recovery by pervaporation.
AB  - The present study deals with the development of an efficient ABE fermentation
      process using mixed substrate strategy for butanol production wherein no acetone
      was produced. For this, glucose was supplemented in the medium containing
      glycerol as main substrate which leads to a higher butanol production of 17.75
      g/L in 72 h by Clostridium acetobutylicum KF158795. Moreover, the high cell
      inoculum also resulted in an increased ABE productivity of 0.46 g/L/h. Further,
      industrial scalability of the process was also successfully validated in a 300 L
      fermenter. Furthermore, potential of the Polymeric (PolyRMem) and Zeolite
      (ZeoMem) membranes for separation of butanol from fermentation broth was also
      studied by testing the pervaporation performance through which the butanol was
      successfully recovered.

PMID- 24316482
TI  - Degradation of high loads of crystalline cellulose and of unpretreated plant
      biomass by the thermophilic bacterium Caldicellulosiruptor bescii.
AB  - The thermophilic bacterium Caldicellulosiruptor bescii grows at 78  degrees C on
      high concentrations (200 g L(-1)) of both crystalline cellulose and unpretreated
      switchgrass, while low concentrations (<20 g L(-1)) of acid-pretreated
      switchgrass inhibit growth. Degradation of crystalline cellulose, but not that of
      unpretreated switchgrass, was limited by nitrogen and vitamin (folate)
      availability. Under optimal conditions, C. bescii solubilized approximately 60%
      of the crystalline cellulose and 30% of the unpretreated switchgrass using
      initial substrate concentrations of 50 g L(-1). Further fermentation of
      crystalline cellulose and of switchgrass was inhibited by organic acid end
      products and by a specific inhibitor of C. bescii growth that did not affect
      other thermophilic bacteria, respectively. Soluble mono- and oligosaccharides,
      organic acids, carbon dioxide, and microbial biomass, quantitatively accounted
      for the crystalline cellulose and plant biomass carbon utilized. C. bescii
      therefore degrades industrially-relevant concentrations of lignocellulosic
      biomass that have not undergone pretreatment thereby demonstrating its potential
      utility in biomass conversion.

PMID- 24316483
TI  - Floatation of granular sludge and its mechanism: a key approach for high-rate
      denitrifying reactor.
AB  - A high-rate denitrifying automatic circulate (DAC) reactor has been developed
      recently, and it is promising to become an alternative in nitrogen removal from
      wastewaters. However, the performance of DAC reactor was disturbed by the
      floatation of granular sludge at high-loads. The results showed that: the
      floatation of granular sludge led to a serious biomass washout and a sharp
      decrease of biomass concentration. The floatation of granular sludge was ascribed
      to a low sludge density originated from the holdup of gaseous products. The
      average density and average gas holdup ratio of floated granular sludge were 913
      kg m(-3) and 11.8% (by volume), respectively. The floatation of granular sludge
      could disappear by releasing gas when sludge was in the state of elastic
      expansion, but it would become worse by holding gas when it entered the plastic
      expansion state. The plastic expansion of granules was significantly correlated
      with the less content of extracellular polymeric substances.

PMID- 24316484
TI  - A comparison of microbial characteristics between the thermophilic and mesophilic
      anaerobic digesters exposed to elevated food waste loadings.
AB  - Thermophilic and mesophilic anaerobic digestion reactors (TR and MR) using food
      waste as substrate were compared with emphasis on microbial responses to
      increasing organic loading rate (OLR). At OLR ranging from 1.0 to 2.5 g VS L(-1)
      d(-1), MR exhibited more stable performance compared to TR in terms of methane
      yield. Amplicons pyrosequencing results revealed the distinct microbial dynamics
      in the two reactors. Primarily, MR had greater richness and evenness of bacteria
      species. With OLR elevated, larger shifts of bacterial phylogeny were observed in
      MR; Methanosaeta dominated in archaeal community in MR while Methanothermobacter
      and Methanoculleus were favored in TR. The high functional redundancy in
      bacterial community integrated with acetoclastic methanogenesis in MR resulted in
      its better performance; whereas delicate interactions between hydrogen-producer
      and hydrogenotrophic methanogens in TR were much more prone to disruption. These
      results are conductive to understanding the microbial mechanisms of low methane
      yield during food waste anaerobic digestion.

PMID- 24316485
TI  - Isolation of Bacillus sp. strains capable of decomposing alkali lignin and their
      application in combination with lactic acid bacteria for enhancing cellulase
      performance.
AB  - Effective biological pretreatment method for enhancing cellulase performance was
      investigated. Two alkali lignin-degrading bacteria were isolated from forest
      soils in Japan and named CS-1 and CS-2. 16S rDNA sequence analysis indicated that
      CS-1 and CS-2 were Bacillus sp. Strains CS-1 and CS-2 displayed alkali lignin
      degradation capability. With initial concentrations of 0.05-2.0 g L(-1), at least
      61% alkali lignin could be degraded within 48 h. High laccase activities were
      observed in crude enzyme extracts from the isolated strains. This result
      indicated that alkali lignin degradation was correlated with laccase activities.
      Judging from the net yields of sugars after enzymatic hydrolysis, the most
      effective pretreatment method for enhancing cellulase performance was a two-step
      processing procedure (pretreatment using Bacillus sp. CS-1 followed by lactic
      acid bacteria) at 68.6%. These results suggest that the two-step pretreatment
      procedure is effective at accelerating cellulase performance.

PMID- 24316486
TI  - Anaerobic digestate as substrate for microalgae culture: the role of ammonium
      concentration on the microalgae productivity.
AB  - In spite of the increasing interest received by microalgae as potential
      alternatives for biofuel production, the technology is still not industrially
      viable. The utilization of digestate as carbon and nutrients source can enhance
      microalgal growth reducing costs and environmental impacts. This work assesses
      microalgal growth utilizing the liquid phase of anaerobic digestate effluent as
      substrate. The effect of inoculum/substrate ratio on microalgal growth was
      studied in a laboratory batch experiment conduced in 0.5L flasks. Results
      suggested that digestate may be an effective substrate for microalgal growth
      promoting biomass production up to 2.6 gTSS/L. Microalgal growth rate was
      negatively affected by a self-shading phenomenon, while biomass production was
      positively correlated with the inoculum and substrate concentrations. Thus, the
      increasing of both digestate and microalgal initial concentration may reduce the
      initial growth rate (MU from 0.9 to 0.04 d(-1)) but significantly enhances
      biomass production (from 0.1 to 2.6 gTSS/L).

PMID- 24316487
TI  - Cystathionine beta-synthase 844ins68 polymorphism is unrelated to susceptibility
      to neural tube defects.
AB  - OBJECTIVE: Cystathionine beta-synthase (CBS) 844ins68 polymorphism has been
      implicated in the development of neural tube defects (NTDs). However, the results
      of different studies are inconsistent. Thus, we conducted a meta-analysis to
      further investigate this association. METHODS: Published studies were retrieved
      from PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data.
      Studies that evaluated the association between CBS 844ins68 polymorphism and NTD
      risk among mothers, children, or fathers were included. The pooled odds ratios
      with 95% confidence interval were calculated using a fixed effects model or a
      random effects model. RESULTS: A total of eight studies on mothers (641 cases and
      1145 controls), eight studies on children (852 cases and 1912 controls), and five
      studies (263 cases and 1562 controls) on fathers were included. The meta-analysis
      revealed no significant association between CBS 844ins68 polymorphism and NTD
      risk among mothers, children, and fathers under either genetic model. CONCLUSION:
      The present meta-analysis indicates that CBS 844ins68 polymorphism is not a good
      predictor of risk for NTDs.

PMID- 24316488
TI  - A genetic variant in p63 (rs17506395) is associated with breast cancer
      susceptibility and prognosis.
AB  - BACKGROUND: p63, homologous to p53, has been investigated to be involved in
      various aspects of tumorigenesis and cancer progression. Recently, we have
      identified a functional single nucleotide polymorphism (SNP) rs17506395 (T>G) in
      p63 which was associated with female reproduction and ovarian cancer development.
      The present study aimed to evaluate the association of rs17506395 genotypes with
      breast cancer susceptibility, clinicopathological characteristics and prognosis.
      PATIENTS AND METHODS: TaqMan assay was used to genotype the rs17506395
      polymorphism. The expression of p63 mRNA was determined by quantitative reverse
      transcription PCR (qRT-PCR). Unconditional logistic regression and univariate Cox
      hazard regression analyses were performed to evaluate the association of
      rs17506395 with breast cancer susceptibility and prognosis respectively. RESULTS:
      First, we found that breast tumors with TT genotype exhibited higher level of p63
      mRNA compared with other genotypes in breast cancer tissues, indicating that
      rs17506395 may be a functional single nucleotide polymorphism in breast cancer.
      Further investigation revealed that the presence of TT genotype was statistically
      correlated with increased risk for breast cancer, compared with genotypes
      containing the G allele (GG and GT). Moreover, a significant association between
      rs17506395 polymorphism and age at diagnosis and status of hormone receptor was
      observed. Consistently, prognostic analysis showed that patients carrying TT
      genotype represent unfavorable survival, suggesting that TT genotype may be a
      biomarker for poor prognosis in breast cancer. CONCLUSION: Our data suggest that
      rs17506395 polymorphism can function as a risk factor and prognostic indicator
      for breast cancer, whereas precise mechanism underlying the function of this
      polymorphism needs further investigation.

PMID- 24316489
TI  - Expression profiles of genes involved in apoptosis and selenium metabolism in
      articular cartilage of patients with Kashin-Beck osteoarthritis.
AB  - Kashin-Beck disease (KBD) is a special type of endemic osteoarthritis. It has
      been suggested that alterations in selenium metabolism and apoptosis play a role
      in KBD. However, the underlying molecular mechanism remains largely unclear. We
      performed a microarray analysis using RNA isolated from cartilages of KBD
      patients and healthy controls, through Significance Analysis of Microarray (SAM)
      software. Functional gene networks and crucial molecules associated with
      differentially expressed genes were investigated via Ingenuity Pathway Analysis
      (IPA) and hub gene analysis. Quantitative real-time PCR was used to check the
      validation of chip test. We identified 52 up-regulated apoptosis-related genes
      and 26 down-regulated selenium-related genes between KBD and controls, and these
      genes associated with the "MYC-mediated apoptosis signaling pathway". We
      confirmed the results from array studies with quantitative real-time PCR
      analysis. Our results suggest that abnormal regulation of selenium metabolism and
      apoptosis through the MYC mediated signaling pathway contributes to the
      pathogenesis of KBD, but the relationship between apoptosis gene and selenium
      gene was not found. 

PMID- 24316490
TI  - Comparative genomic analysis shows that Streptococcus suis meningitis isolate
      SC070731 contains a unique 105K genomic island.
AB  - Streptococcus suis (SS) is an important swine pathogen worldwide that
      occasionally causes serious infections in humans. SS infection may result in
      meningitis in pigs and humans. The pathogenic mechanisms of SS are poorly
      understood. Here, we provide the complete genome sequence of S. suis serotype 2
      (SS2) strain SC070731 isolated from a pig with meningitis. The chromosome is
      2,138,568bp in length. There are 1933 predicted protein coding sequences and
      96.7% (57/59) of the known virulence-associated genes are present in the genome.
      Strain SC070731 showed similar virulence with SS2 virulent strains HA9801 and
      ZY05719, but was more virulent than SS2 virulent strain P1/7 in the zebrafish
      infection model. Comparative genomic analysis revealed a unique 105K genomic
      island in strain SC070731 that is absent in seven other sequenced SS2 strains.
      Further analysis of the 105K genomic island indicated that it contained a
      complete nisin locus similar to the nisin U locus in S. uberis strain 42, a
      prophage similar to S. oralis phage PH10 and several antibiotic resistance genes.
      Several proteins in the 105K genomic island, including nisin and RelBE toxin
      antitoxin system, contribute to the bacterial fitness and virulence in other
      pathogenic bacteria. Further investigation of newly identified gene products,
      including four putative new virulence-associated surface proteins, will improve
      our understanding of SS pathogenesis.

PMID- 24316491
TI  - Using an adapted form of the picture exchange communication system to increase
      independent requesting in deafblind adults with learning disabilities.
AB  - The current study assessed the effectiveness of an adapted form of the Picture
      Exchange Communication System (PECS) in increasing independent requesting in
      deafblind adults with learning disabilities. PECS cards were created to
      accommodate individual needs, including adaptations such as enlarging photographs
      and using swelled images which consisted of images created on raised line drawing
      paper. Training included up to Phase III of PECS and procedures ensuring
      generalizations across individuals and contexts were included. The effects of the
      intervention were evaluated using a multiple baseline design across participants.
      Results demonstrated an increase in independent requesting with each of the
      participants reaching mastery criterion. These results suggest that PECS, in
      combination with some minor adaptations, may be an effective communicative
      alternative for individuals who are deafblind and have learning impairments. 

PMID- 24316492
TI  - Quality of life among parents of children with autistic disorder: a sample from
      the Arab world.
AB  - BACKGROUND: A growing body of research has sought to examine issues associated
      with the Quality of Life (QoL) of parents of children with Autistic Disorder.
      However, no studies have examined the QoL of Arab parents whose parenting
      experience is expected to be substantially different from that of their western
      counterparts. Therefore, the purposes of this study were: (1) to examine
      differences in the QoL between fathers and mothers of children with Autistic
      Disorder in a sample from an Arab country, and (2) to examine the psychosocial
      correlates of the QoL of Arab parents of children with Autistic Disorder.
      METHODS: Self-administered questionnaires on parents' QoL, stress, coping
      strategies, and demographic characteristics were completed by 184 parents of
      children with Autistic Disorder. The participants were recruited using the
      convenience sampling design. RESULTS: Fathers and mothers of children with
      Autistic Disorder showed no significant differences in their physical,
      psychological, social, and environmental health. Further, both parents showed
      almost similar bivariate correlations between the reported QoL levels and their
      parenting stress, coping strategies, and demographic characteristics. CONCLUSION:
      This is the first study to examine the QoL of parents of children with Autistic
      Disorder in the Arab world and, in doing so, it highlighted the distinct lack of
      research in this area. The QoL of Arab parents of children with Autistic Disorder
      crosses lines with their stress levels, coping strategies, demographic
      characteristics, and to some extent their cultural context.

PMID- 24316493
TI  - The microenvironment in T-cell lymphomas: emerging themes.
AB  - Peripheral T-cell lymphomas (PTCLs) are heterogeneous and uncommon malignancies
      characterized by an aggressive clinical course and a mostly poor outcome with
      current treatment strategies. Despite novel insights into their pathobiology
      provided by recent genome-wide molecular studies, several entities remain poorly
      characterized. In addition to the neoplastic cell population, PTCLs have a
      microenvironment component, composed of non-tumor cells and stroma, which is
      quantitatively and qualitatively variable, and which may have an effect on their
      pathological and clinical features. The best example is provided by
      angioimmunoblastic T-cell lymphoma (AITL), a designation reflecting the typical
      vascularization and reactive immunoblastic content of the tumor tissues. In this
      disease, a complex network of interactions between the lymphoma cells and the
      microenvironment exists, presumably mediated by the neoplastic T cells with
      follicular helper T-cell properties. A better understanding of the crosstalk
      between neoplastic T or NK cells and their microenvironment may have important
      implications for guiding the development of novel therapies. 

PMID- 24316496
TI  - Phase segregation of superconductivity and ferromagnetism at the LaAlO3/SrTiO3
      interface.
AB  - The highly conductive two-dimensional electron gas formed at the interface
      between insulating SrTiO3 and LaAlO3 shows low-temperature superconductivity
      coexisting with inhomogeneous ferromagnetism. The Rashba spin-orbit interaction
      with the in-plane Zeeman field of the system favors p(x) +/- ip(y)-wave
      superconductivity at finite momentum. Owing to the intrinsic disorder at the
      interface, the role of spatial inhomogeneity in the superconducting and
      ferromagnetic states becomes important. We find that, for strong disorder, the
      system breaks up into mutually excluded regions of superconductivity and
      ferromagnetism. This inhomogeneity-driven electronic phase separation accounts
      for the unusual coexistence of superconductivity and ferromagnetism observed at
      the interface.

PMID- 24316495
TI  - Synthesis, structural characterization and dielectric properties of
      (C6H9N2)2(Hg0.75Cd0.25)Cl4 compound.
AB  - The present paper undertakes the study of a title compound whose structure is
      (C6H9N2)2(Hg0.75Cd0.25)Cl4. The centrosymmetric compound crystallizes in the
      triclinic space group P-1, with a=7.580(7) A; b=8.572(8) A; c=15.433(13) A;
      alpha=84.49(5) degrees ; beta=89.13(5) degrees ; gamma=68.53(5) degrees  and Z=2.
      The crystal structure was solved and refined to R (int)=0.0212 using 7932
      independent reflections. The atomic arrangement shows an alternation of organic
      and inorganic layers. Between layers, the cohesion is performed via N-H?Cl
      hydrogen bonding, yet in the organic sheets, cations are further connected to
      classical pi-pi stacking. The Infrared and Raman spectra of this compound
      reported from 400 to 4000 cm(-1) confirmed the presence of the principal bands
      assigned to the internal modes of organic cation. Solid-state (13)C and (111)Cd
      CP-MAS-NMR spectra are reported. The dielectric study of this compound has been
      measured, in order to determine the sigma(d.c) conductivity which is thermally
      activated with activation energy about 1.5 eV.

PMID- 24316494
TI  - HTLV-1 clonality in adult T-cell leukaemia and non-malignant HTLV-1 infection.
AB  - Human T lymphotropic virus type 1 (HTLV-1) causes a range of chronic inflammatory
      diseases and an aggressive malignancy of T lymphocytes known as adult T-cell
      leukaemia/lymphoma (ATLL). A cardinal feature of HTLV-1 infection is the presence
      of expanded clones of HTLV-1-infected T cells, which may persist for decades. A
      high viral burden (proviral load) is associated with both the inflammatory and
      malignant diseases caused by HTLV-1, and it has been believed that the
      oligoclonal expansion of infected cells predisposes to these diseases. However,
      it is not understood what regulates the clonality of HTLV-1 in vivo, that is, the
      number and abundance of HTLV-1-infected T cell clones. We review recent advances
      in the understanding of HTLV-1 infection and disease that have come from high
      throughput quantification and analysis of HTLV-1 clonality in natural infection. 

PMID- 24316497
TI  - Evaluating school wellness policy in curbing childhood obesity in Anchorage,
      Alaska.
AB  - In 2006, the Anchorage School District implemented a school wellness policy to
      address the problem of obesity among its elementary-aged students. We assessed
      whether the addition of this policy is effective in protecting or preventing
      students from becoming overweight/obese over time. The methods involved following
      two cohorts of students for 5 years, a cohort not exposed and a cohort exposed to
      the policy. The results show that exposure to the policy does not significantly
      protect or prevent students from becoming overweight/obese. However, we found
      that regardless of being exposed to the policy, boys (odds ratio [OR] = 1.12),
      ethnic minorities, (OR = 1.18), and students from low socioeconomic backgrounds
      (OR = 1.44) were more likely to remain or become overweight/obese. Our findings
      suggest that factors outside the school may be impacting students'
      overweight/obese status. Efforts to curb the problem of childhood obesity should
      extend to the children's communities and homes. 

PMID- 24316498
TI  - Isolation and characterisation of two cDNAs encoding transglutaminase from
      Atlantic cod (Gadus morhua).
AB  - Two cDNAs encoding transglutaminase (TG) were identified in a subtractive cDNA
      library prepared from the head kidney of poly I:C stimulated Atlantic cod (Gadus
      morhua). Full-length TG-1 and TG-2 cDNA were cloned from the head kidney by a
      reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification
      of cDNA ends (RACE). The deduced amino acid (aa) sequence for TG-1 was 695 aa
      with an estimated molecular mass of 78.3 kDa, while TG-2 was a 698 aa protein
      with an estimated molecular mass of 78.8 kDa. The two proteins were named TG-1
      and TG-2 and both possess transglutaminase/protease-like homologous domains (TGc)
      and full conservation of amino acids cysteine, histidine, and aspartate residues
      that form the catalytic triad. Sequence analysis showed high similarity (93.1%)
      with Alaska pollock TG, and the TGs were grouped together with TGs from chum
      salmon, Japanese flounder, Nile tilapia, and red sea bream in addition to Alaska
      pollock in phylogenetic analysis. Interestingly, they showed different tissue
      distribution with highest constitutive expression in reproductive and
      immunological organs, indicating important roles in these organs. Furthermore,
      the up-regulation of TG-1 and TG-2 in head kidney after stimulating Atlantic cod
      with poly I:C suggested a role of TGs in immune response in Atlantic cod. 

PMID- 24316499
TI  - Growth, feed intake and immune responses of orange-spotted grouper (Epinephelus
      coioides) exposed to low infectious doses of ectoparasite (Cryptocaryon
      irritans).
AB  - To explore the effect of low-dose Cryptocaryon irritans infection on growth,
      feeding and antiparasitic immunity of orange-spotted grouper (Epinephelus
      coioides), this study utilized C. irritans at concentrations of 5500
      theronts/fish (Group I, 1/10 of 96 h LC50) or 11,000 theronts/fish (Group II) to
      infect E. coioides weighing 38 g on average at week 0, 2 and 4, respectively.
      Food consumption was recorded daily; the fish were weighed weekly; serum
      immobilizing titer (SIT), and acid phosphatase (ACP), alkaline phosphatase (AKP),
      superoxide dismutase (SOD), lysozyme (LZM) activity were recorded every 2 weeks;
      the fish were treated with lethal dose (70,000 theronts/fish) of C. irritans in
      the 8th week and death number were recorded. The result shows that in the 1st
      week after the first infection, the fish's weight gain (WG), length gain (LG),
      and specific growth rate (SGR) dropped as parasite dose increased, and WG, SGR
      values were negative; while, after the 2nd and the 3rd infection, no significant
      differences were detected among the three groups. These results indicated that
      the 1st infection affected the fish most, while the following infections were
      protected by some immunity. In the 3rd, 7th, and 8th week, condition factor (CF)
      increased with the increased infectious dose, indicating that the parasite
      affected body length more than body weight. As the experiment went on,
      accumulated food consumption (AFC) of all three groups steadily grew (control >
      Group I > Group II). But on the 2nd day after the first infection, daily food
      consumption (DFC) of Group I and II significantly dropped, the decline of Group
      II was greater than that of Group I, DFC recovered in the following week, with
      Group I earlier than Group II. After the 2nd infection, DFC of Group I and II
      dropped again, Group II still dropped more than Group I, and both groups
      recovered on the 3rd day after infection. The 3rd infection caused no significant
      difference in week food consumption (WFC). These results indicated that a higher
      dose of infection causes a greater drop in FC and a slower recovery. Weekly feed
      conversion ratio (WFCR) values of Group I and II in the 1st week was negative; in
      the 2nd week, WFCR was lower in the group infected by a higher dose of parasite;
      while in the 3rd and following weeks, no significant pattern was observed.
      Accumulate feed conversion ratio (AFCR) dropped as the infectious dose increased
      (control > Group I > Group II), AFCR of Group I and II reached above 0 in the 2nd
      and 4th week, respectively. From the 4th week on, the inter-group AFCR of the 3
      groups still took on a declining trend with the increased infectious dose but the
      gap became smaller. One week after the first infection, SIT of Group I and Group
      II were 0; one week after the 2nd infection, SIT reached up to 8 (Group I) and 16
      (Group II) respectively; and after the 3rd infection, SIT further increased and
      peaked in the 7th week. When challenged by lethal dose of C. irritans, fish of
      all 3 groups began to die since the 3rd day after infection, and the final deaths
      were 14, 12 and 8 for the control group, Group I and Group II, respectively. ACP
      activity in the 1st, 5th, 7th but the 3rd week was higher in the experiment group
      than that in the control group, but no significant difference was detected
      between Group I and II throughout the experiment. AKP activity increased as the
      infectious dose increased, but the difference among the three groups gradually
      became less obvious in latter infections, and no significant difference can be
      detected in the end. SOD activity increased with infection dose at each time
      point, while both group I and group II had their SOD activities first increased
      and then decreased as times of infection increased. The LZM activity of the two
      infection groups increased as the infectious times increased. Combining the
      results on growth and feeding, we speculated that the fish's physiological
      condition stabilized after 3 rounds of infection. To sum up, low-dose infection
      by C. irritans can induce the fish's immunity, but at the cost of decreasing food
      intake, decreased food conversion, and lagged growth.

PMID- 24316500
TI  - Role of CD4(+) and CD8alpha(+) T cells in protective immunity against
      Edwardsiella tarda infection of ginbuna crucian carp, Carassius auratus
      langsdorfii.
AB  - Edwardsiella tarda is an intracellular pathogen that causes edwardsiellosis in
      fish. Our previous study suggests that cell-mediated immunity (CMI) plays an
      essential role in protection against E. tarda infection. In the present study, we
      adoptively transferred T-cell subsets sensitized with E. tarda to isogenic naive
      ginbuna crucian carp to determination the T-cell subsets involved in protecting
      fish from E. tarda infection. Recipients of CD4(+) and CD8alpha(+) cells acquired
      significant resistance to infection with E. tarda 8 days after sensitization,
      indicating that helper T cells and cytotoxic T lymphocytes plays crucial roles in
      protective immunity to E. tarda. Moreover, transfer of sensitized CD8alpha(+)
      cells up-regulated the expression of genes encoding interferon-gamma (IFN-gamma)
      and perforin, suggesting that protective immunity to E. tarda involves cell
      mediated cytotoxicity and interferon-gamma-mediated induction of CMI. The results
      establish that CMI plays a crucial role in immunity against E. tarda. These
      findings provide novel insights into understanding the role of CMI to
      intracellular pathogens of fish.

PMID- 24316501
TI  - Injury prediction in a side impact crash using human body model simulation.
AB  - BACKGROUND: Improved understanding of the occupant loading conditions in real
      world crashes is critical for injury prevention and new vehicle design. The
      purpose of this study was to develop a robust methodology to reconstruct injuries
      sustained in real world crashes using vehicle and human body finite element
      models. METHODS: A real world near-side impact crash was selected from the Crash
      Injury Research and Engineering Network (CIREN) database. An average sedan was
      struck at approximately the B-pillar with a 290 degree principal direction of
      force by a lightweight pickup truck, resulting in a maximum crush of 45 cm and a
      crash reconstruction derived Delta-V of 28 kph. The belted 73-year-old midsized
      female driver sustained severe thoracic injuries, serious brain injuries,
      moderate abdominal injuries, and no pelvic injury. Vehicle finite element models
      were selected to reconstruct the crash. The bullet vehicle parameters were
      heuristically optimized to match the crush profile of the simulated struck
      vehicle and the case vehicle. The Total Human Model for Safety (THUMS) midsized
      male finite element model of the human body was used to represent the case
      occupant and reconstruct her injuries using the head injury criterion (HIC), half
      deflection, thoracic trauma index (TTI), and pelvic force to predict injury risk.
      A variation study was conducted to evaluate the robustness of the injury
      predictions by varying the bullet vehicle parameters. RESULTS: The THUMS thoracic
      injury metrics resulted in a calculated risk exceeding 90% for AIS3+ injuries and
      70% risk of AIS4+ injuries, consistent with her thoracic injury outcome. The
      THUMS model predicted seven rib fractures compared to the case occupant's 11 rib
      fractures, which are both AIS3 injuries. The pelvic injury risk for AIS2+ and
      AIS3+ injuries were 37% and 2.6%, respectively, consistent with the absence of
      pelvic injury. The THUMS injury prediction metrics were most sensitive to bullet
      vehicle location. The maximum 95% confidence interval width for the mean injury
      metrics was only 5% demonstrating high confidence in the THUMS injury prediction.
      CONCLUSIONS: This study demonstrates a variation study methodology in which human
      body models can be reliably used to robustly predict injury probability
      consistent with real world crash injury outcome.

PMID- 24316502
TI  - Effectiveness of red light running camera enforcement program in reducing
      crashes: evaluation using "before the installation", "after the installation",
      and "after the termination" data.
AB  - The focus of this manuscript is to evaluate and assess the effectiveness of red
      light running camera (RLC) enforcement program in reducing crashes at signalized
      intersections. Data from January 1997 to December 2010 for thirty-two signalized
      intersections in the city of Charlotte, North Carolina, where RLCs were installed
      between August 1998 and August 2000 and terminated in fall 2006, were gathered,
      analyzed, and compared for "before the installation", "after the installation",
      and "after the termination" periods. Descriptive analysis and paired t-tests were
      performed using rear-end, sideswipe, left-turn, angle, and right-turn crashes as
      well as the number of total crashes. The expected number of total crashes, had
      RLC enforcement program not been implemented, was computed using the empirical
      bayes (EB) method and compared to the actual number of total crashes for "after
      the installation" and "after the termination" periods. Results obtained indicate
      that RLC enforcement program leads to an increase in sideswipe and rear-end
      crashes at >= 50% of the signalized intersections. It is effective in reducing
      total crashes at 50% and 16% of the thirty-two signalized intersections when
      analyzed considering "before the installation - after the installation" and
      "before the installation - after the termination" scenarios, respectively.
      Benefits due to reduction in the number of total crashes may be higher if RLC
      enforcement program is implemented at signalized intersections with (1) total
      entering vehicles per day less than 40,000, (2) fewer than 20 rear-end crashes
      per year, or (3) fewer than 5 sideswipe crashes per year.

PMID- 24316503
TI  - A cross-sectional observational study of helmet use among motorcyclists in Wa,
      Ghana.
AB  - Motorcyclists' injuries and fatalities are a major public health concern in many
      developing countries including Ghana. This study therefore aimed to investigate
      the prevalence of helmet use among motorcyclists in Wa, Ghana. The method used
      involved a cross-sectional roadside observation at 12 randomly selected sites
      within and outside the CBD of Wa. A total of 14,467 motorcyclists made up of
      11,360 riders and 3107 pillion riders were observed during the study period. Most
      observed riders (86.5%) and pillion riders (61.7%) were males. The overall
      prevalence of helmet use among the observed motorcyclists was 36.9% (95% CI: 36.1
      37.7). Helmet use for riders was 45.8% (95% CI: 44.8-46.7) whilst that for
      pillion riders was 3.7% (95 CI: 3.0-4.4). Based on logistic regression analysis,
      higher helmet wearing rates were found to be significantly associated with female
      gender, weekdays, morning periods and at locations within the CBD. Riders at
      locations outside the CBD were about 7 times less likely to wear a helmet than
      riders within the CBD (48.9% compared to 42.3%; chi(2)(1)=49.526; p<0.001). The
      study concluded that despite the existence of a national helmet legislation that
      mandates the use of helmets by both riders and pillion riders on all roads in
      Ghana, helmet use is generally low in Wa. This suggests that all stakeholders in
      road safety should jointly intensify education on helmet use and pursue rigorous
      enforcement on all road types especially at locations outside the CBD to improve
      helmet use in Wa. 

PMID- 24316504
TI  - Modifying behaviour to reduce over-speeding in work-related drivers: an objective
      approach.
AB  - The goal of this study was to utilise an objective measurement tool, via an on
      board Diagnostic tool (OBDII), to explore the effectiveness of a behaviour
      modification intervention designed to reduce over-speed violations in a group of
      work-related drivers. It was predicted that over-speed violations would be
      decreased following participation in a behaviour modification intervention where
      drivers received weekly feedback on their speeding performance and goal setting
      exercises. The final analysis included the on-road behaviour of 16 drivers, all
      of whom completed each stage of the intervention programme. As predicted, over
      speed violations significantly decreased from pre-test to post-test, after
      controlling for kilometres driven. These findings offer practical guidance for
      industry in developing interventions designed to improve work-related driving
      behaviour. 

PMID- 24316505
TI  - Traffic violations in Guangdong Province of China: speeding and drunk driving.
AB  - The number of speeding- and drunk driving-related injuries in China surged in the
      years immediately preceding 2004 and then began to decline. However, the percent
      decrease in the number of speeding and drunk driving incidents (decrease by 22%)
      is not proportional to the corresponding percent decrease in number of automobile
      accident-related injuries (decrease by 47%) from the year 2004 to 2010 (Traffic
      Management Bureau, Ministry of Public Security, Annual Statistical Reports on
      Road Traffic Accidents). Earlier studies have established traffic violations as
      one of the major risks threatening road safety. In this study, we examine in
      greater detail two important types of traffic violation events, speeding and
      drunk driving, and attempt to identify significant risk factors associated with
      these types of traffic violations. Risk factors in several different dimensions,
      including driver, vehicle, road and environmental factors, are considered. We
      analyze the speeding (N=11,055) and drunk driving (N=10,035) data for the period
      2006-2010 in Guangdong Province, China. These data, obtained from the Guangdong
      Provincial Security Department, are extracted from the Traffic Management Sector
      Specific Incident Case Data Report and are the only comprehensive and official
      source of traffic accident data in China. Significant risk factors associating
      with speeding and drunk driving are identified. We find that several factors are
      associated with a significantly higher probability of both speeding and drunk
      driving, particularly male drivers, private vehicles, the lack of street lighting
      at night and poor visibility. The impact of other specific and unique risk
      factors for either speeding or drunk driving, such as hukou, road type/grades,
      commercial vehicles, compulsory third party insurance and vehicle safety status,
      also require particular attention. Legislative or regulatory measures targeting
      different vehicle types and/or driver groups with respect to the various driver,
      vehicle, road and environmental risk factors can subsequently be devised to
      reduce the speeding and drunk driving rates. As the country with the highest
      number of traffic accident fatalities in the world, applying these findings in
      workable legislation and enforcement to reduce speeding and drunk driving rates
      will save tens of thousands of lives. 

PMID- 24316506
TI  - Bayesian methodology to estimate and update safety performance functions under
      limited data conditions: a sensitivity analysis.
AB  - In road safety studies, decision makers must often cope with limited data
      conditions. In such circumstances, the maximum likelihood estimation (MLE), which
      relies on asymptotic theory, is unreliable and prone to bias. Moreover, it has
      been reported in the literature that (a) Bayesian estimates might be
      significantly biased when using non-informative prior distributions under limited
      data conditions, and that (b) the calibration of limited data is plausible when
      existing evidence in the form of proper priors is introduced into analyses.
      Although the Highway Safety Manual (2010) (HSM) and other research studies
      provide calibration and updating procedures, the data requirements can be very
      taxing. This paper presents a practical and sound Bayesian method to estimate
      and/or update safety performance function (SPF) parameters combining the
      information available from limited data with the SPF parameters reported in the
      HSM. The proposed Bayesian updating approach has the advantage of requiring fewer
      observations to get reliable estimates. This paper documents this procedure. The
      adopted technique is validated by conducting a sensitivity analysis through an
      extensive simulation study with 15 different models, which include various prior
      combinations. This sensitivity analysis contributes to our understanding of the
      comparative aspects of a large number of prior distributions. Furthermore, the
      proposed method contributes to unification of the Bayesian updating process for
      SPFs. The results demonstrate the accuracy of the developed methodology.
      Therefore, the suggested approach offers considerable promise as a methodological
      tool to estimate and/or update baseline SPFs and to evaluate the efficacy of road
      safety countermeasures under limited data conditions. 

PMID- 24316507
TI  - Surrogate safety measure for evaluating rear-end collision risk related to
      kinematic waves near freeway recurrent bottlenecks.
AB  - This study presents a surrogate safety measure for evaluating the rear-end
      collision risk related to kinematic waves near freeway recurrent bottlenecks
      using aggregated traffic data from ordinary loop detectors. The attributes of
      kinematic waves that accompany rear-end collisions and the traffic conditions at
      detector stations spanning the collision locations were examined to develop the
      rear-end collision risk index (RCRI). Together with RCRI, standard deviations in
      occupancy were used to develop a logistic regression model for estimating rear
      end collision likelihood near freeway recurrent bottlenecks in real-time. The
      parameters in the logistic regression models were calibrated using collision data
      gathered from the 6-mile study site between 2006 and 2007. Findings indicated
      that an additional unit increase in RCRI results in increasing the odds of rear
      end collision by 21.1%, a unit increase in standard deviation of upstream
      occupancy increases the odds by 19.5%, and a unit increase in standard deviation
      of downstream occupancy increases the odds by 18.7%. The likelihood of rear-end
      collisions is highest when the traffic approaching from upstream is near capacity
      state while downstream traffic is highly congested. The paper also reports on the
      findings from comparing the predicted number of rear-end collisions at the study
      site using the proposed model with the observed traffic collision data from 2008.
      The proposed model's true positive rates were higher than those of existing real
      time crash prediction models. 

PMID- 24316508
TI  - Hyperexcitability to electrical stimulation and accelerated muscle fatiguability
      of taut bands in rats.
AB  - OBJECTIVE: Myofascial trigger points contribute significantly to musculoskeletal
      pain and motor dysfunction and may be associated with accelerated muscle
      fatiguability. The aim of this study was to investigate the electrically induced
      force and fatigue characteristics of muscle taut bands in rats. METHODS: Muscle
      taut bands were dissected out and subjected to trains of electrical stimulation.
      The electrical threshold intensity for muscle contraction and maximum contraction
      force (MCF), electrical intensity dependent fatigue and electrical frequency
      dependent fatigue characteristics were assessed in three different sessions (n=10
      each) and compared with non-taut bands in the biceps femoris muscle. RESULTS: The
      threshold intensity for muscle contraction and MCF at the 10th, 15th and 20th
      intensity dependent fatigue stimuli of taut bands were significantly lower than
      those of non-taut bands (all p<0.05). The MCF at the 15th and 20th intensity
      dependent fatigue stimuli of taut bands were significantly lower than those at
      the 1st and 5th stimuli (all p<0.01). The MCF in the frequency dependent fatigue
      test was significantly higher and the stimulus frequency that induced MCF was
      significantly lower for taut bands than for non-taut bands (both p<0.01).
      CONCLUSIONS: The present study demonstrates that the muscle taut band itself was
      more excitable to electrical stimulation and significantly less fatigue resistant
      than normal muscle fibres.

PMID- 24316509
TI  - Acupuncture for acute non-specific low back pain: a randomised, controlled,
      double-blind, placebo trial.
AB  - OBJECTIVE: To assess the efficacy of Yamamoto's acupuncture method on pain, drug
      intake, functional capacity and quality of life for the treatment of acute non
      specific low back pain (ANLBP). METHODS: A prospective, randomised, parallel
      group, double-blind, placebo-controlled trial was performed in 80 men and women
      with ANLBP who were randomly assigned to five acupuncture sessions (intervention
      group (IG), n=40) and to five non-penetrating acupuncture sessions (sham group
      (SG), n=40). Patients were evaluated at baseline and at 3, 7, 14, 21 and 28 days.
      The measurements used were: visual analogue scale (VAS) for cumulative pain
      (before intervention, VAS1) and immediate pain (after intervention, VAS2);
      function (Roland-Morris Disability Questionnaire (RM)); quality of life (SF-36);
      improvement rating; and number of anti-inflammatory tablets taken. The primary
      endpoint was a decrease of at least 2 cm in VAS1. RESULTS: Pain VAS improved
      significantly in the IG from day 14 onwards compared with the SG, but the
      difference did not reach the prespecified clinically relevant value of 2 cm. The
      IG was significantly superior to the SG in the following outcomes: cumulative
      pain, function, pain (SF-36) and vitality (SF-36) at days 14, 21 and 28 (p<0.05);
      limitation in physical aspects (SF-36) at all times (p=0.007 and p=0.02); and
      functional capacity (SF-36) at days 21 and 28 (p<0.05). The IG also took
      significantly fewer anti-inflammatory tablets than the SG (p=0.004) at all
      evaluation times and the improvement rating was better than the SG (p<0.001).
      CONCLUSIONS: Yamamoto's new scalp acupuncture was more effective than sham
      treatment with regard to decrease in pain and anti-inflammatory intake as well as
      improving functional status and quality of life for patients with ANLBP.
      CLINICALTRIALSGOV: NCT 01124955.

PMID- 24316510
TI  - Pantethine treatment is effective in recovering the disease phenotype induced by
      ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model.
AB  - Pantothenate kinase-associated neurodegeneration, caused by mutations in the
      PANK2 gene, is an autosomal recessive disorder characterized by dystonia,
      dysarthria, rigidity, pigmentary retinal degeneration and brain iron
      accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2,
      responsible for the phosphorylation of pantothenate or vitamin B5 in the
      biosynthesis of co-enzyme A. A Pank2 knockout (Pank2(-/-)) mouse model did not
      recapitulate the human disease but showed azoospermia and mitochondrial
      dysfunctions. We challenged this mouse model with a low glucose and high lipid
      content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta
      oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a
      general impairment of bioenergetic metabolism. Only Pank2(-/-) mice fed with a
      ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like
      syndrome characterized by severe motor dysfunction, neurodegeneration and
      severely altered mitochondria in the central and peripheral nervous systems.
      These mice also showed structural alteration of muscle morphology, which was
      comparable with that observed in a patient with pantothenate kinase-associated
      neurodegeneration. We here demonstrate that pantethine administration can prevent
      the onset of the neuromuscular phenotype in mice suggesting the possibility of
      experimental treatment in patients with pantothenate kinase-associated
      neurodegeneration. 

PMID- 24316511
TI  - Downregulation of histone deacetylase 1 by microRNA-520h contributes to the
      chemotherapeutic effect of doxorubicin.
AB  - Doxorubicin induces DNA damage to exert its anti-cancer function. Histone
      deacetylase 1 (HDAC1) can protect the genome from DNA damage. We found that
      doxorubicin specifically downregulates HDAC1 protein expression and identified
      HDAC1 as a target of miR-520h, which was upregulated by doxorubicin. Doxorubicin
      induced cell death was impaired by exogenous HDAC1 or by miR-520h inhibitor.
      Moreover, HDAC1 reduced the level of gammaH2AX by preventing the interaction of
      doxorubicin with DNA. In summary, doxorubicin downregulates HDAC1 protein
      expression, by inducing the expression of HDAC1-targeting miR-520h, to exacerbate
      DNA-doxorubicin interaction. The upregulation of HDAC1 protein may contribute to
      drug resistance of human cancer cells and targeting HDAC1 is a promising strategy
      to increase the clinical efficacy of DNA damage-inducing chemotherapeutic drugs. 

PMID- 24316513
TI  - miR-329 suppresses the growth and motility of neuroblastoma by targeting KDM1A.
AB  - MicroRNAs (miRNAs) act as key regulators of multiple cancers. miR-329 functions
      as a tumor suppressor in some malignancies. However, its role in neuroblastoma
      remains poorly understood. We found that miR-329 was decreased in metastatic
      tumor tissues compared with matched primary tumor tissues. Forced overexpression
      of miR-329 substantially suppressed cell proliferation, colony formation,
      migration, and invasion of neuroblastoma cells. Lysine-specific demethylase 1
      (KDM1A) was found to be a target of miR-329. Furthermore, down-regulation of
      KDM1A by shRNA performed similar effects with overexpression of miR-329.
      Overexpression of KDM1A partially reversed the tumor suppressive effects of miR
      329 in neuroblastoma cells. Collectively, miR-329 may suppress neuroblastoma cell
      growth and motility partially by targeting KDM1A. 

PMID- 24316512
TI  - Recent advances in mammalian protein production.
AB  - Mammalian protein production platforms have had a profound impact in many areas
      of basic and applied research, and an increasing number of blockbuster drugs are
      recombinant mammalian proteins. With global sales of these drugs exceeding US$120
      billion per year, both industry and academic research groups continue to develop
      cost effective methods for producing mammalian proteins to support pre-clinical
      and clinical evaluations of potential therapeutics. While a wide range of
      platforms have been successfully exploited for laboratory use, the bulk of recent
      biologics have been produced in mammalian cell lines due to the requirement for
      post translational modification and the biosynthetic complexity of the target
      proteins. In this review we highlight the range of mammalian expression platforms
      available for recombinant protein production, as well as advances in technologies
      for the rapid and efficient selection of highly productive clones. 

PMID- 24316514
TI  - Serelaxin in acute heart failure patients with preserved left ventricular
      ejection fraction: results from the RELAX-AHF trial.
AB  - AIMS: Serelaxin is effective in relieving dyspnoea and improving multiple
      outcomes in acute heart failure (AHF). Many AHF patients have preserved ejection
      fraction (HFpEF). Given the lack of evidence-based therapies in this population,
      we evaluated the effects of serelaxin according to EF in RELAX-AHF trial. METHODS
      AND RESULTS: RELAX-AHF randomized 1161 AHF patients to 48-h serelaxin (30
      MUg/kg/day) or placebo within 16 h from presentation. We compared the effects of
      serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage
      between preserved (>=50%) and reduced (<50%, HFrEF) EF. HFpEF was present in 26%
      of patients. Serelaxin induced a similar dyspnoea relief in HFpEF vs. HFrEF
      patients by visual analogue scale-area under the curve (VAS-AUC) through Day 5
      [mean change, 461 (-195, 1117) vs. 397 (10, 783) mm h, P = 0.87], but had
      possibly different effects on the proportion of patients with moderately or
      markedly dyspnoea improvement by Likert scale at 6, 12, and 24 h [odds ratio for
      favourable response, 1.70 (0.98, 2.95) vs. 0.85 (0.62, 1.15), interaction P =
      0.030]. No differences were encountered in the effect of serelaxin on short- or
      long-term outcome between HFpEF and HFrEF patients including cardiovascular death
      or hospitalization for heart/renal failure through Day 60, cardiovascular death
      through Day 180, and all-cause death through Day 180. Similar safety and changes
      in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate
      aminotransferases) were found in both groups. CONCLUSIONS: In AHF patients with
      HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective
      in relieving dyspnoea and had a similar effect on short- and long-term outcome,
      including survival improvement.

PMID- 24316515
TI  - Advanced paternal age and mortality of offspring under 5 years of age: a register
      based cohort study.
AB  - STUDY QUESTION: Do children born to fathers of advanced age have an increased
      risk of dying before the age of 5 years? SUMMARY ANSWER: Children born to fathers
      aged 40 years or more have an increased risk of dying in early childhood due to
      an excess risk of fatal congenital anomalies, malignancies and external causes.
      WHAT IS KNOWN ALREADY: Advanced paternal age has previously been associated with
      adverse reproductive outcomes and some long-term health problems in the
      offspring. This is possibly due to specific point mutations, a condition known to
      increase in the sperm with increasing paternal age. STUDY DESIGN, SIZE, DURATION:
      A Danish population-based register study, designed as a prospective cohort study,
      of 1 575 521 live born children born from 1978 to 2004. The age of the child (in
      days) was used as the underlying time and the children entered the cohort the day
      they were born and were followed until 31 December 2009. The children were
      censored on date of turning 5 years, date of death or date of emigration,
      whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from
      population-covering registers from Statistics Denmark including the Integrated
      Database for Labour Market Research, the Medical Birth Registry and the Registry
      of Causes of Death was linked using the unique civil registry number. Hazard
      ratios (HR) with 95% confidence intervals (CI) were used to estimate the risk of
      under-five mortality. The effect of paternal age was examined using restricted
      cubic splines and paternal age groups. MAIN RESULTS AND THE ROLE OF CHANCE:
      Compared with children born to fathers aged 30-34 years, a statistically
      significant excess risk was found for children born to fathers aged 40-44 years
      [HR: 1.10 (95% CI: 1.00-1.21)] and children born to fathers aged 45+ years [HR:
      1.16 (95% CI: 1.02-1.32)]. When only looking at 1-5 year olds, the relative risk
      (HR) among children born to fathers aged 40-44 years increased to 1.24 (95% CI:
      1.00-1.53) and the risk in the oldest paternal age group (45+ years) rose to 1.65
      (95% CI: 1.24-2.18). The results suggest that the elevated risk for children of
      fathers aged 40 years or more was primarily attributed to an elevated risk of
      dying from congenital malformations, malignancies and external causes.
      LIMITATIONS, REASONS FOR CAUTION: Specific causes of death might be
      misclassified; however, this is not likely to be dependent on paternal age. In
      some cases, the biological father may differ from the father registered. This
      misclassification is most likely non-differential. WIDER IMPLICATIONS OF THE
      FINDINGS: The excess risk of mortality among children born to older fathers is in
      accordance with the literature. The association needs further attention as it can
      provide valuable knowledge of the etiology of genetic diseases. Also, the
      association could become of greater importance in the future if the proportion of
      fathers aged 40+ years keeps growing. STUDY FUNDING/COMPETING INTEREST (S): None.

PMID- 24316516
TI  - Fat chance!

PMID- 24316518
TI  - Dietary glycotoxins exacerbate progression of experimental fatty liver disease.
AB  - BACKGROUND & AIMS: Advanced glycation end-products (AGEs) levels are high in
      western diets and contribute to tissue injury via activation of RAGE (receptor
      for AGEs) and generation of reactive oxygen species (ROS). Here, we determined if
      high dietary AGE intake worsens progression of non-alcoholic fatty liver disease
      (NAFLD). METHODS: Male Sprague Dawley rats were fed a methionine choline
      deficient (MCD) diet for 6 weeks before 6 weeks of a high AGE MCD diet through
      baking. They were compared with animals on MCD diet or a methionine choline
      replete (MCR) diet alone for 12 weeks. Hepatic ROS, triglycerides, biochemistry,
      picro-sirius morphometry, hepatic mRNA expression and immunohistochemistry were
      determined. Primary hepatic stellate cells (HSCs) from both MCR and MCD animals
      were exposed to AGEs. ROS, proliferation and mRNA expression were determined.
      RESULTS: The high AGE MCD diet increased hepatic AGE content and elevated
      triglycerides, NADPH dependent superoxide production, HNE adducts, steatosis,
      steatohepatitis (CD43, IL-6, TNF-alpha) and fibrosis (alpha-SMA, CTGF, COL1A,
      picrosirius) compared to MCD alone. In HSCs, AGEs significantly increased ROS
      production, bromodeoxyuridine proliferation and MCP-1, IL-6, alpha-SMA, and RAGE
      expression in HSCs from MCD but not MCR animals. These effects were abrogated by
      RAGE or NADPH oxidase blockade. CONCLUSIONS: In the MCD model of NAFLD, high
      dietary AGEs increases hepatic AGE content and exacerbates liver injury,
      inflammation, and liver fibrosis via oxidative stress and RAGE dependent
      profibrotic effects of AGEs on activated HSCs. This suggests that pharmacological
      and dietary strategies targeting the AGE/RAGE pathway could slow the progression
      of NAFLD.

PMID- 24316517
TI  - Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin
      sensitivity.
AB  - BACKGROUND & AIMS: Obesity has been associated with changes in the composition
      and function of the intestinal microbiota. Modulation of the microbiota by
      antibiotics also alters bile acid and glucose metabolism in mice. Hence, we
      hypothesized that short term administration of oral antibiotics in humans would
      affect fecal microbiota composition and subsequently bile acid and glucose
      metabolism. METHODS: In this single blinded randomized controlled trial, 20 male
      obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin
      500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week
      of therapy, fecal microbiota composition (Human Intestinal Tract Chip
      phylogenetic microarray), fecal and plasma bile acid concentrations as well as
      insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose
      tracer) were measured. RESULTS: Vancomycin reduced fecal microbial diversity with
      a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory
      increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly,
      vancomycin decreased fecal secondary bile acids with a simultaneous postprandial
      increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal
      bile acid concentrations were predominantly associated with altered Firmicutes.
      Finally, administration of vancomycin decreased peripheral insulin sensitivity
      (p<0.05). Amoxicillin did not affect any of these parameters. CONCLUSIONS: Oral
      administration of vancomycin significantly impacts host physiology by decreasing
      intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin
      sensitivity in subjects with metabolic syndrome. These data show that intestinal
      microbiota, particularly of the Firmicutes phylum contributes to bile acid and
      glucose metabolism in humans. This trial is registered at the Dutch Trial
      Register (NTR2566).

PMID- 24316520
TI  - Affinity chromatography, two-dimensional electrophoresis, adapted immunodepletion
      and mass spectrometry used for detection of porcine and piscine heparin-binding
      human plasma proteins.
AB  - Heparin-binding proteins in human plasma were studied using affinity
      chromatography columns with porcine (2mL, 10.7mg capacity) and piscine heparin
      (5mL, 2.7mg capacity). Two-dimensional electrophoresis (Bio-Rad Protean II gel
      system with 16cm*16cm gels using isoelectric focusing (IEF) and nonequilibrium pH
      gradient gel electrophoresis (NEPHGE)), Bruker Ultraflex MALDI-TOF mass
      spectrometry and immunoblotting (NovaBlot semidry discontinuous blotting) were
      used for unfractionated plasma. This revealed electropherograms with differences
      between porcine and piscine heparin-binding and totally 17 different fibrinogen
      variants from all 3 chains. Immunodepletion was used to remove fibrinogen (42.1mg
      anti-human fibrinogen in 8.4mL resin) and serum albumin (0.42mg binding capacity
      in 14mL resin) and porcine and piscine heparin-binding proteins were identified
      using liquid chromatography-mass spectrometry (Ultimate 3000 NanoLC with Acclaim
      PepMap 100 column (50cm*75MUm)-LTQ Orbitrap Mass XL). In total, the binding of 76
      putative or acknowledged biomarkers are shown. Of the identified proteins, 14 are
      not previously shown to be heparin-binding, such as the low concentration
      proteins lipocalin-1 and tropomyosin and a hitherto not detected protein in
      plasma, zinc finger protein 483. The putative heparin-binding sequences were
      analyzed. The results suggest that the combination of group specific affinity and
      adapted immunodepletion chromatography could be useful in the study of the plasma
      proteome. 

PMID- 24316519
TI  - Central immune overactivation in the presence of reduced plasma corticosterone
      contributes to swim stress-induced hyperalgesia.
AB  - Although it is widely known that immunological, hormonal and nociceptive
      mechanisms are altered by exposure to repeated stress, the interplaying roles of
      each function in the development of post-stress hyperalgesia are not completely
      clear. Thus, we wanted to establish how interleukin 1-beta (IL-1beta),
      corticosterone and microglia interact to contribute in the development of
      hyperalgesia following repeated forced swim. Rats were subjected to either forced
      swim, sham swim or non-conditioned. Each group was then treated with minocycline,
      ketoconazole, or saline. Thermal nociception was measured via the hot plate test,
      before and after the behavioral conditioning, whereas blood and lumbar spinal
      cord tissue samples were obtained at the end of the protocol. Serum levels of
      corticosterone, spinal tissue concentration of IL-1beta and spinal OX-42 labeling
      (microglial marker) were determined. Rats exposed to forced swim stress developed
      thermal hyperalgesia along with elevated spinal tissue IL-1beta, increased OX-42
      labeling and relatively diminished serum corticosterone. Pre-treatment with
      minocycline and ketoconazole prevented the development of thermal hyperalgesia
      and the increase in IL-1beta, without significantly modifying serum
      corticosterone. These results suggest that the development of forced swim-induced
      thermal hyperalgesia requires the simultaneous presence of increased spinal IL
      1beta, microglial activation, and relatively decreased serum corticosterone. 

PMID- 24316521
TI  - Method development and validation for simultaneous determination of lumefantrine
      and its major metabolite, desbutyl lumefantrine in human plasma using RP-HPLC/UV
      detection.
AB  - A simple, specific, precise and rapid RP-HPLC-UV method was developed for
      simultaneous determination of lumefantrine and its metabolite desbutyl
      lumefantrine in human plasma. Experimental parameters were optimized and the
      method was validated according to standard guidelines. The method showed adequate
      separation for lumefantrine and desbutyl lumefantrine and best resolution was
      achieved with Supelco Discovery HS C18 RP (150mm*4.6mm, 5MUm) column using
      acetonitrile and 0.05% trifluroacetic acid (70:30, v/v) as a mobile phase pumped
      at a flow rate of 1.0ml/min and wavelength of 335nm. The method was linear over
      the concentration range of 10-12,000ng/ml. The lower limit of detection (LLOD)
      and lower limit of quantification (LLOQ) for lumefantrine were 10.0 and
      18.0ng/ml, while for desbutyl lumefantrine were 7.5 and 15.0ng/ml, respectively.
      The proposed method was efficiently applied for determination of lumefantrine and
      desbutyl lumefantrine concentrations in plasma samples for pharmacokinetic
      studies. 

PMID- 24316522
TI  - Application of ultra-performance liquid chromatography coupled with quadrupole
      time-of-flight mass spectrometry to determine the metabolites of orientin
      produced by human intestinal bacteria.
AB  - An ultra performance liquid chromatography/quadrupole time-of-flight mass
      spectrometry (UPLC-Q-TOF/MS) with MetaboLynxTM software combined with mass defect
      filtering (MDF) method were provided for orientin metabolism study. The
      chromatographic separation was performed on a 1.7MUm particle size Syncronis C18
      column using gradient elution system. The components were identified and
      confirmed according to the mass spectrometric fragmentation mechanisms, MS/MS
      fragment ions and relevant literature by means of electrospray ionization mass
      spectrometry in negative ion mode. With this method, a total of three metabolites
      were identified based on retention time and MS/MS data. The results illustrated
      that deglycosylation, dehydroxylation and acetylation were the major metabolic
      pathways of orientin in vitro by human intestinal bacteria. Additionally, colonic
      bacteria were screened for bacteria involved in the conversion of orientin. A
      gram-negative anaerobic bacterium, strain 45, was newly isolated from healthy
      human feces. This strain, which was able to cleave the C-glycoside of orientin to
      produce luteolin and generate some other metabolites, had the similarity of
      95.44% with Enterococcus casseliflavus and was named Enterococcus sp. 45 based on
      16S rRNA sequence analysis. In this paper, the metabolic routes, metabolites of
      oreintin produced by the intestinal bacteria and the Enterococcus sp. 45 were
      investigated for the first time. 

PMID- 24316523
TI  - Structural elucidation of the metabolites of lapachol in rats by liquid
      chromatography-tandem mass spectrometry.
AB  - Lapachol is a natural naphthoquinone compound derived from Bignoniaceae (Tabebuia
      sp.) that possesses a range of significant biological activities. Nine phase I
      and four phase II metabolites of lapachol in rat bile were firstly elucidated and
      identified using a sensitive LC-ESI-MS(n) method. The molecular structures of the
      metabolites have been presented on the basis of the characteristics of their
      precursor and product ions, as well as their fragmentation mechanisms and
      chromatographic retention times. The results indicated that the phase I
      metabolites were predominantly biotransformed by the hydroxylation, semiquinone
      hydrogenation at the oxygen position or a side chain rearrangement. The phase II
      metabolites were identified as the glucuronidated conjugates which showed a
      characteristic neutral loss of 176Da. Based on the results of this research, we
      have proposed the metabolic pathways for lapachol in rats. This work has provided
      novel information for the in vivo lapachol metabolism which could be used to
      develop a novel drug candidate, as well as a better understanding of the safety
      and efficacy of the drug. 

PMID- 24316524
TI  - Fast determination of paraquat in plasma and urine samples by solid-phase
      microextraction and gas chromatography-mass spectrometry.
AB  - A simple, sensitive and reliable gas chromatographic-mass spectrometric method
      (GC-MS) for quantifying paraquat concentration in biological samples has been
      developed, using ethyl paraquat as an internal standard. The method involved the
      procedures of sodium borohydride-nickel chloride (NaBH4-NiCl2) reduction and
      solid-phase microextraction (SPME) of the perhydrogenated products. GC-MS was
      used to identify and quantify the analytes in selected ion monitoring (SIM) mode.
      Under the optimal conditions, recoveries in plasma and urine samples were 94.00
      99.85% and 95.00-100.34%, respectively. Excellent sample clean-up was observed
      and good linearities (r=0.9982 for plasma sample and 0.9987 for urine sample)
      were obtained in the range of 0.1-50MUg/mL. The limits of detection (S/N=3) were
      0.01MUg/mL in plasma and urine samples. The intra-day precision was less than
      8.43%, 4.19% (n=3), and inter-day precision was less than 10.90%, 10.49% (n=5)
      for plasma and urine samples, respectively. This method was successfully applied
      to the analysis of the biological samples collected from a victim who died as a
      result of ingestion of paraquat. 

PMID- 24316525
TI  - Determination of urinary alpha-aminoadipic semialdehyde by LC-MS/MS in patients
      with congenital metabolic diseases.
AB  - This paper describes a full detailed high performance liquid
      chromatography/tandem mass spectrometry method for the identification and
      quantification of human urine alpha-aminoadipic semialdehyde, biomarker of
      pyridoxine-dependent epilepsy. The ionization mode of the electrospray interface
      was negative and the metabolite was detected in the multiple reaction monitoring
      mode. Intra-day and inter-day laboratory precision were 4.64% and 7.30%,
      respectively, total run time was 3.5min. The calibration curve was linear between
      0.25 and 10nmol with a correlation coefficient of the calibration line
      (R(2)>=0.9984); the limit of quantification was 0.25nmol within the control
      group. This simple, fast, high reproducible and robust procedure facilitates a
      rapid diagnosis of patients with pyridoxine-dependent epilepsy and can also be
      used to confirm the elevated urinary alpha-aminoadipic semialdehyde excretion in
      patients with other metabolic diseases as molybdenum cofactor and isolated
      sulphite oxidase deficiencies. 

PMID- 24316527
TI  - Automated on-line column-switching high performance liquid chromatography isotope
      dilution tandem mass spectrometry method for the quantification of bisphenol A,
      bisphenol F, bisphenol S, and 11 other phenols in urine.
AB  - Human exposure to bisphenol A (BPA) is widespread. However, in recent years,
      bisphenol analogs such as bisphenol S (BPS) and bisphenol F (BPF) are replacing
      BPA in the production of some consumer products. Because human exposure to these
      alternative bisphenols may occur, biomonitoring of these bisphenol analogs is
      warranted. In the present study, we developed and validated a sensitive and
      selective method that uses on-line solid phase extraction coupled to high
      performance liquid chromatography-isotope dilution tandem mass spectrometry with
      peak focusing to measure BPA, BPF, BPS, and 11 other environmental phenols in
      urine. The method required a small amount of sample (100MUL) and minimal sample
      pretreatment. The limits of detection were 0.03ng/mL (BPS), 0.06ng/mL (BPF),
      0.10ng/mL (BPA), and ranged from 0.1ng/mL to 1.0ng/mL for the other 11 phenols.
      In 100 urine samples collected in 2009-2012 from a convenience group of anonymous
      adults in the United States, of the three bisphenols, we detected BPA at the
      highest frequency and median concentrations (95%, 0.72ng/mL), followed by BPS
      (78%, 0.13ng/mL) and BPF (55%, 0.08ng/mL). This sensitive, rugged, and labor and
      cost-effective method could be used for the analysis of large number of samples
      for epidemiologic studies. 

PMID- 24316526
TI  - HPLC separation of human serum albumin isoforms based on their isoelectric
      points.
AB  - Human serum albumin (HSA) is the most abundant protein in plasma. Cys34, the only
      free Cys residue, is the predominant plasma thiol and a relevant sacrificial
      antioxidant. Both in vivo circulating HSA and pharmaceutical preparations are
      heterogeneous with respect to the oxidation state of Cys34. In this work, we
      developed an external pH gradient chromatofocusing procedure that allows the
      analysis of the oxidation status of HSA in human plasma and biopharmaceutical
      products based on the different apparent isoelectric points and chemical
      properties of the redox isoforms. Specifically, reduced-mercury blocked HSA (HSA
      SHg(+)), HSA with Cys34 oxidized to sulfenic acid (HSA-SOH) and HSA oxidized to
      sulfinate anion (HSA-SO2(-)) can be separated with resolutions of 1.4 and 3.1
      (first and last pair) and hence quantified and purified. In addition, an N
      terminally degraded isoform (HSA3-585) in different redox states can be resolved
      as well. Confirmation of the identity of the chromatofocusing isolated isoforms
      was achieved by high resolution whole protein MS. It is proposed that the
      chromatofocusing procedure can be used to produce more exact and complete
      descriptions of the redox status of HSA in vivo and in vitro. Finally, the
      scalability capabilities of the chromatofocusing procedure allow for the
      preparation of highly pure standards of several redox isoforms of HSA. 

PMID- 24316528
TI  - Development of lipidomic platform and phosphatidylcholine retention time index
      for lipid profiling of rosuvastatin treated human plasma.
AB  - A simple and fast methodology to detect and identify multiple classes of lipid
      from human plasma is developed utilizing ultra-performance liquid chromatography
      quadrupole time-of-flight mass spectrometry (UPLC-QTOF) as lipidomics platform.
      All the conditions for the sample preparation and analytical instruments were
      optimized in detail to detect nine lipid classes (phosphatidylserine (PS),
      phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine
      (PC), triacylglyceride (TG), phosphatidylinositol (PI), lysophosphatidylcholine
      (LysoPC), lysophosphatidic acid (LysoPA), and sphingomyelin (SM)), which are the
      most important biologically active lipids but have different characteristics.
      Finally, the plasma was prepared after a liquid-liquid extraction with a mixture
      of chloroform/methanol (1:2v/v) including salting out by adding 0.15M of NaCl and
      the residue after evaporation was reconstituted with a mixture of
      chloroform/methanol (1:1v/v) to dissolve all lipids which have different
      polarity. The chromatographic conditions were set up such that mobile phase (A)
      comprised 10mM ammonium acetate in 40% acetonitrile and mobile phase (B)
      comprised 10mM ammonium acetate in acetonitrile:isopropanol=10:90(v/v) with
      ACQUITY BEH C18 as the stationary phase. In particular, a retention time index of
      PC was constructed by analyzing known standards to confirm each variant of PC
      without the use of any additional standards in every experiment. The lipidomic
      methodology and the retention time index of PC were applied to analyze the
      lipidomic profiling of human plasma from rosuvastatin (lipid lowering drug)
      treated subjects. In the developed lipidomic platform, all lipids were
      successfully analyzed within 16min and PCs could be confirmed with the PC
      retention time index. In rosuvastatin treatment, the lipid profiling was changed
      in all the eight lipid classes. The level of SM, TG, PI and PE decrease
      significantly but LysoPCs and PCs were whether decreased or increased. Those
      results indicated that the plasma level of overall lipids decreased by drug
      response, however, the changes in the lipids which are important components for
      biological membrane such as LysoPC and PC were more complicated, and it could be
      related to the side effect of rousuvastatin. In conclusion, it was found that our
      lipidomic methodology and the PC retention time index provided not only overall
      lipidomic information but also profiled specific information of drug response. 

PMID- 24316529
TI  - A rapid, sensitive method for quantitative analysis of underivatized amino acids
      by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AB  - The quantitation of free amino acids from physiologic samples is essential for
      diagnosing and monitoring patients with inherited metabolic disorders. Current
      methods are hindered by long preparative and/or analysis times, expensive
      reagents, and often suboptimal performance characteristics. To overcome these
      challenges, a improved method for amino acid analysis using liquid chromatography
      tandem mass spectrometry (LC-MS/MS) has been developed and validated. Samples
      were deproteinized with sulfosalicylic acid and supernatants diluted with
      tridecafluoroheptanoic acid. Chromatographic separation of amino acids occurred
      using two columns, with conditions favoring resolution of isobaric compounds and
      minimizing ion suppression. Eluted compounds were detected by selective reaction
      monitoring, and quantitated by relating peak areas of amino acids to externally
      run standards. Validation studies evaluated linearity, within- and between-run
      imprecision, lower limits of detection and quantification for 33 amino acids, and
      correlation with the Biochrom 30 Amino Acid Analyzer. Total run time including re
      equilibration was 15min per sample. Within-run precision averaged 2.8% for all
      compounds, with an average linear correlation coefficient of 0.995. The majority
      of compounds were reliably quantitated at <=0.1MUM. Between-run precision
      averaged 4.0%. Results showed excellent correlation with the Biochrom 30 amino
      acid analyzer with an average overall correlation of 0.908. We conclude that our
      method is extremely sensitive, specific and reproducible and represents an
      improvement over other currently available technologies. 

PMID- 24316530
TI  - Validation of absolute axial neutron flux distribution calculations with MCNP
      with 197Au(n,gamma)198Au reaction rate distribution measurements at the JSI TRIGA
      Mark II reactor.
AB  - The calculation of axial neutron flux distributions with the MCNP code at the JSI
      TRIGA Mark II reactor has been validated with experimental measurements of the
      (197)Au(n,gamma)(198)Au reaction rate. The calculated absolute reaction rate
      values, scaled according to the reactor power and corrected for the flux
      redistribution effect, are in good agreement with the experimental results. The
      effect of different cross-section libraries on the calculations has been
      investigated and shown to be minor. 

PMID- 24316531
TI  - Betulinic acid and 1,25(OH)2 vitamin D3 share intracellular signal transduction
      in glucose homeostasis in soleus muscle.
AB  - The effect of betulinic acid on glycemia and its mechanism of action compared
      with 1,25(OH)2 vitamin D3 in rat muscle were investigated. Betulinic acid
      improved glycemia, induced insulin secretion and increased the glycogen content
      and glucose uptake in muscle tissue. Additionally, the integrity of both PI3K and
      the cytoskeleton is necessary for the stimulatory action of betulinic acid in
      glucose uptake. The genomic effect was apparent, since cycloheximide and PD98059
      nullified the stimulatory effect of betulinic acid on glucose uptake. Therefore,
      although this compound did not modify the DNA transcription, the protein
      translation was significantly improved. Also, betulinic acid increased the GLUT4
      immunocontent and its translocation was corroborated by GLUT4 localization at the
      plasma membrane (after 180 min). On the other hand, the effect of 1,25(OH)2
      vitamin D3 on glucose uptake is not mediated by PI3K and microtubule activity. In
      contrast, the nuclear activity of 1,25(OH)2 vitamin D3 is necessary to trigger
      glucose uptake. In addition, the increased DNA transcription and GLUT4
      immunocontent provide evidence of a mechanism by which 1,25(OH)2 vitamin D3
      contributes to glycemia. In conclusion, betulinic acid acts as an insulin
      secretagogue and insulinomimetic agent via PI3K, MAPK and mRNA translation and
      partially shares the genomic pathway with 1,25(OH)2 vitamin D3 to upregulate the
      GLUT4. In summary, betulinic acid regulates glycemia through classical insulin
      signaling by stimulating GLUT4 synthesis and translocation. In addition, it does
      not cause hypercalcemia, which is highly significant from the drug discovery
      perspective.

PMID- 24316532
TI  - FTIR spectroscopic comparison of serum from lung cancer patients and healthy
      persons.
AB  - The incidence and mortality of lung cancer remains so high that it is very urgent
      to develop an effective method for early detection of lung cancer. Serum can
      reflect physiological and pathological changes of human body, so FTIR
      spectroscopy was used to compare lung cancer patients' and healthy persons' serum
      in this study. The A1080/A1170 ratio might be potentially useful for
      distinguishing lung cancer patients' serum from healthy persons' serum. Moreover,
      the result of curve fitting indicated that the ratios of alpha-helix/antiparallel
      beta-sheet were lower for lung cancer patients' serum than those for healthy
      persons' serum. These results indicated that IR spectra of serum might be
      potentially useful for detecting lung cancer. 

PMID- 24316533
TI  - A highly sensitive dual-readout assay based on poly(A) and gold nanoparticles for
      palmatine hydrochloride.
AB  - This report presents a highly sensitive, poly(A)-stabilized gold nanoparticle
      based assay with dual readouts (resonance light scattering and colorimetric) for
      detecting palmatine hydrochloride (PaH) in real samples. The detection mechanism
      is based on the fact that palmatine hydrochloride has strong affinity to poly(A),
      which can stabilize gold nanoparticles at high ionic strength, and cause the
      aggregation of poly(A)-stabilized AuNPs, resulting in the enhanced resonance
      light scattering (RLS). At the same time, the color change of poly(A)-stabilized
      AuNPs solution is from red to blue via purple. Thus a highly sensitive RLS assay
      for PaH has been developed with a linear range of 0.023-2.5 MUg/mL. The limit of
      detection (LOD, 3sigma) is 2.3 ng/mL. In this work, the reaction mechanism of
      this system was investigated by scanning electron microscope (SEM), dark-field
      light scattering images (DLSI), dynamiclight scattering (DLS) and circular
      dichroism (CD). This proposed method was also applied successfully for the
      determination of PaH in pharmaceutical preparations and urine samples with
      RSD?4.0%. The results are in good agreement with those from the official method.

PMID- 24316534
TI  - A new platinum complex with tryptophan: synthesis, structural characterization,
      DFT studies and biological assays in vitro over human tumorigenic cells.
AB  - A new platinum(II) complex with the amino acid L-tryptophan (trp), named Pt-trp,
      was synthesized and characterized. Elemental, thermogravimetric and ESI-QTOF mass
      spectrometric analyses led to the composition [Pt(C11H11N2O2)2]?6H2O. Infrared
      spectroscopic data indicate the coordination of trp to Pt(II) through the oxygen
      of the carboxylate group and also through the nitrogen atom of the amino group.
      The (13)C CP/MAS NMR spectroscopic data confirm coordination through the oxygen
      atom of the carboxylate group, while the (15)N CP/MAS NMR data confirm
      coordination of the nitrogen of the NH2 group to the metal. Density functional
      theory (DFT) studies were applied to evaluate the cis and trans coordination
      modes of trp to platinum(II). The trans isomer was shown to be energetically more
      stable than the cis one. The Pt-trp complex was evaluated as a cytotoxic agent
      against SK-Mel 103 (human melanoma) and Panc-1 (human pancreatic carcinoma) cell
      lines. The complex was shown to be cytotoxic over the considered cells. 

PMID- 24316535
TI  - Crystal growth and spectroscopic characterization of Aloevera amino acid added
      lithium sulfate monohydrate: a non-linear optical crystal.
AB  - Non-linear optical crystals of lithium sulfate monohydrate added with Aloevera
      amino acid were grown successfully by slow evaporation technique moderately at
      low cost. Initially the Aloevera amino acid extract was prepared from the 3 years
      old plant leaves and the amino acids present in that were identified by high
      performance liquid chromatography. The grown crystal was clear, transparent and
      they attained the size about 1.3*0.8*0.6 cm(3) within a time span of 20-25 days.
      The crystal was subjected to Fourier Transform Infrared Spectroscopy, UV-Vis-NIR,
      thermal and mechanical studies. Proton nuclear magnetic resonance, thin layer
      chromatography and colorimetric estimation techniques are carried out to confirm
      and identify the amino acid in the grown crystal.

PMID- 24316536
TI  - Fluorescence enhancement of quercetin complexes by silver nanoparticles and its
      analytical application.
AB  - It is found that the plasmon effect of silver nanoparticles (AgNPs) helps to
      enhance the fluorescence intensity of the quercetin (Qu) and nucleic acids
      system. Qu exhibited strong fluorescence enhancement when it bound to nucleic
      acids in the presence of AgNPs. Based on this, a sensitive method for the
      determination of nucleic acids was developed. The detection limits for the
      nucleic acids (S/N=3) were reduced to the ng mL(-1) level. The interaction
      mechanism of the AgNPs-fish sperm DNA (fsDNA)-Qu system was also investigated in
      this paper. This complex system of Qu and AgNPs was also successfully used for
      the detection of nucleic acids in agarose gel electrophoresis analysis.
      Preliminary results indicated that AgNPs also helped to improve sensitivity in
      the fluorescence image analysis of Qu combined with cellular contents in
      Arabidopsis thaliana protoplasts.

PMID- 24316537
TI  - A thermally labile copper (II) complex with hetero N- and O-donor ligands:
      crystal structure, Hirshfeld surfaces, thermal and luminescent properties.
AB  - A new complex ([Cu(L1)2(H2O]2]?2H2O, 1) derived from a hetero N- and O-donor
      ligand 5-methyl-imidazole-3-carboxylic acid (L1H) has been synthesized and
      characterized. Comparisons between [Cu(L1)2(H2O]2]?2H2O, [Co(L2)(H2O]2?H2O (2),
      and [Cu(L2)2H2O]?H2O (L2H=5-methyl-isoxazole-3-carboxylic acid) revealed that the
      coordinated water molecules play a key role in the construction of crystal
      structures: two coordinated water molecules in the axial positions lead to single
      deck 1D chain and 3D motif while one coordinated water molecule resulted to
      double-deck 1D chain and 2D stacking motif. Molecular Hirshfeld surfaces revealed
      that complexes 1 and 2 were supported mainly by H-H, C-H?pi, and O-H?O
      intermolecular interactions. The room temperature solid state luminescent
      properties of complexes 1 and 2 were all shown as two distinct bands, which
      attribute to ligand-metal charge transfer and metal purterbed ligand centered
      emission.

PMID- 24316538
TI  - The molecular structure of the vanadate mineral mottramite [PbCu(VO4)(OH)] from
      Tsumeb, Namibia--a vibrational spectroscopic study.
AB  - We have studied a mineral sample of mottramite PbCu(VO4)(OH) from Tsumeb, Namibia
      using a combination of scanning electron microscopy with EDX, Raman and infrared
      spectroscopy. Chemical analysis shows principally the elements V, Pb and Cu. Ca
      occurs as partial substitution of Pb as well as P and As in substitution to V.
      Minor amounts of Si and Cr were also observed. The Raman band of mottramite at
      829 cm(-1), is assigned to the nu1 symmetric (VO4(-)) stretching mode. The
      complexity of the spectra is attributed to the chemical composition of the Tsumeb
      mottramite. The nu3 antisymmetric vibrational mode of mottramite is observed as
      very low intensity bands at 716 and 747 cm(-1). The series of Raman bands at 411,
      439, 451 cm(-1) and probably also the band at 500 cm(-1) are assigned to the
      (VO4(-)) nu2 bending mode. The series of Raman bands at 293, 333 and 366 cm(-1)
      are attributed to the (VO4(-)) nu4 bending modes. The nu3, nu3 and nu4 regions
      are complex for both minerals and this is attributed to symmetry reduction of the
      vanadate unit from Td to Cs.

PMID- 24316539
TI  - Using low-frequency IR spectra for the unambiguous identification of metal ion
      ligand coordination sites in purpose-built complexes.
AB  - One of the aims of our long-term research is the identification of metal ion
      ligand coordination sites in bioinspired metal ion-C- or N-protected amino acid
      (histidine, tyrosine, cysteine or cystine) complexes immobilised on the surface
      of chloropropylated silica gel or Merrifield resin. In an attempt to reach this
      goal, structurally related, but much simpler complexes have been prepared and
      their metal ion-ligand vibrations were determined from their low-frequency IR
      spectra. The central ions were Mn(II), Co(II), Ni(II) or Cu(II) and the ligands
      (imidazole, isopropylamine, monosodium malonate) were chosen to possess only one
      type of potential donor group. The low-frequency IR spectra were taken of the
      complexes for each ion-ligand combination and the typical metal ion-functional
      group vibration bands were selected and identified. The usefulness of the
      obtained assignments is demonstrated on exemplary immobilised metal ion-protected
      amino acid complexes. 

PMID- 24316540
TI  - Study of photocatalytic activity of ZnS quantum dots as efficient nanoparticles
      for removal of methyl violet: effect of ferric ion doping.
AB  - Zinc sulfide quantum dots (QDs), as pure and doped with Fe(3+), were prepared for
      photodecolorization of methyl violet (MV), as a model dye, under UV light
      irradiation. The syntheses of QDs were carried out using a simple chemical co
      precipitation method. The prepared samples were characterized by various
      techniques including X-ray diffraction, transmission electron microscopy, UV-Vis
      spectrophotometry and flame atomic absorption spectroscopy. The influences of
      operational parameters on the decolorization of MV such as dopant content, pH,
      dosage of nanophotocatalyst, UV irradiation time and initial dye concentration
      were studied. The results showed that the QDs presented high efficiency for MV
      decolorization, and doping of ZnS QDs with Fe(3+) enhanced the efficiency and
      rate of dye removal. Finally, the reproducibility and kinetic model of the dye
      degradation were discussed. 

PMID- 24316541
TI  - A novel highly selective colorimetric sensor for aluminum (III) ion using Schiff
      base derivative.
AB  - A novel colorimetric sensor, 2-hydroxy naphthaldehyde isonicotinoyl hydrazone
      (HINH), was easily synthesized by the condensation of isoniazid and 2-hydroxy-1
      naphthaldehyde. The as-prepared compound showed effective colorimetric single
      selectivity and high sensitivity for aluminum cation in CH3CN/H2O (1:3) binary
      solutions. The detection limit is 1.0*10(-8) M Al(3+) based on UV-vis changes.

PMID- 24316542
TI  - Heterotrimetallic Ru(II)/Pd(II)/Ru(II) complexes: synthesis, crystalstructure,
      spectral characterization, DFT calculation and antimicrobial study.
AB  - New ruthenium(II) mononuclear complexes of the type [RuCl2(PPh3)2(eta(2)
      triamine)] (2) [RuCl(PPh3)2(eta(3)-triamine)]Cl (5) (triemine=N(1)-(2-aminoethyl)
      1,2-ethanediamine) have been synthesized by reacting [RuCl2(PPh3)3] (1) with one
      mole equivalent of N(1)-(2-aminoethyl)-1,2-ethanediamine in dichloromethane.
      Reaction of (2) with half-equivalent of (PhCN)2PdCl2 or Pd(OAc)2 in
      dichloromethane as a solvent afforded two novel heterotrimetallic Ru(II)-Pd(II)
      Ru(II) complexes, [Ru(II)Cl2(PPh3)2(triamine)]2[Pd(II)X2](X=Cl, OAc) (3 and 4),
      bearing bioactive ligand. The progress of the undertaken reactions was monitored
      by (31)P{1H} NMR and FTIR. Crystal structure of complex 2 was confirmed by X-ray
      diffraction. The absorption spectrum of 2 in dichloromethane was modeled by time
      dependent density functional theory (TD-DFT). The in vitro antimicrobial studies
      of complex 2-5 against an array of microorganisms (bacteria and fungi) were
      conducted. Complexes 3 and 4 exhibit high dual antibacterial and antifungal
      activity inhibiting microorganisms possibly via hydrolytic pathway which further
      evidenced by electrochemical analyses. The complexes 3 and 4 show a high
      inhibitory activity at 200 MUg/ml concentration, suggesting that complexes 3 and
      4 are two efficient catalytic inhibitor of microorganisms and further, they
      should be tested against cancer strains.

PMID- 24316543
TI  - Theoretical investigations of the structures and electronic spectra of Zn(II) and
      Ni(II) complexes with cyclohexylamine-N-dithiocarbamate.
AB  - The ground-state structures of two ligands cyclohexylamine-N-dithiocarbamate (L)
      and PPh3 and four complexes [Zn(L)2] (A), [Ni(L)2] (B), [Zn(L)2PPh3] (C), and
      [Ni(L)2PPh3] (D) are optimized by M06, B3LYP, and B3PW91 methods with the same
      mixed basis set. As compared with the experimental data of other complexes
      containing the Ni-P bond, the result obtained by M06/6-31+G(d)-LANL2DZ method is
      finally regarded as accurate and reliable for this project. Based on the
      optimized geometries, the compositions of molecular orbitals are analyzed and the
      absorption spectra are simulated. When one more ligand PPh3 is coordinated, the
      lowest-lying transition energy presents red-shift; while it shows blue-shift when
      the metal coordination center change from Ni to Zn with the same ligands. The
      detailed transition characters related with the absorption spectrum are assigned.
      In all the key transitions, it is hard to find the contribution from Zn atom. On
      the contrary, the d orbital of Ni atom contributes a lot for the HOMO and LUMO of
      complexes B and D. Consequently, the transition characters of Zn(II) and Ni(II)
      complexes are different. 

PMID- 24316544
TI  - Evaluation of FTIR spectroscopy as diagnostic tool for colorectal cancer using
      spectral analysis.
AB  - The aim of this study is to confirm FTIR spectroscopy as a diagnostic tool for
      colorectal cancer. 180 freshly removed colorectal samples were collected from 90
      patients for spectrum analysis. The ratios of spectral intensity and relative
      intensity (/I1460) were calculated. Principal component analysis (PCA) and
      Fisher's discriminant analysis (FDA) were applied to distinguish the malignant
      from normal. The FTIR parameters of colorectal cancer and normal tissues were
      distinguished due to the contents or configurations of nucleic acids, proteins,
      lipids and carbohydrates. Related to nitrogen containing, water, protein and
      nucleic acid were increased significantly in the malignant group. Six parameters
      were selected as independent factors to perform discriminant functions. The
      sensitivity for FTIR in diagnosing colorectal cancer was 96.6% by discriminant
      analysis. Our study demonstrates that FTIR can be a useful technique for
      detection of colorectal cancer and may be applied in clinical colorectal cancer
      diagnosis. 

PMID- 24316545
TI  - 2-{2-[4-(Dimethylamino)phenyl]-6-methyl-4H-pyran-4-ylidene}malononitrile: a
      colorimetric and fluorescent chemosensor for low pH values.
AB  - For developing intramolecular charge transfer (ICT) chemosensors for low pH
      values, 2-{2-[4-(dimethylamino)phenyl]-6-methyl-4H-pyran-4-ylidene}malononitrile
      (DPM) was designed and synthesized. The spectroscopic and pH-sensing properties
      of DPM were investigated by UV-Vis and fluorescence spectroscopy. This sensor
      exhibited a pH-dependent ratiometric absorption property in the range of pH 0-3,
      along with a reversible color change from yellow to colorless with increasing
      acid concentration. The fluorescence intensity of the sensor was increased with
      increasing pH within the pH range of 0-2. 

PMID- 24316546
TI  - Comprehensive quantum chemical and spectroscopic (FTIR, FT-Raman, 1H, 13C NMR)
      investigations of O-desmethyltramadol hydrochloride an active metabolite in
      tramadol--an analgesic drug.
AB  - O-desmethyltramadol is one of the main metabolites of tramadol widely used
      clinically and has analgesic activity. The FTIR and FT-Raman spectra of O
      desmethyl tramadol hydrochloride are recorded in the solid phase in the regions
      4000-400 cm(-1) and 4000-100 cm(-1), respectively. The observed fundamentals are
      assigned to different normal modes of vibration. Theoretical studies have been
      performed as its hydrochloride salt. The structure of the compound has been
      optimised with B3LYP method using 6-31G(**) and cc-pVDZ basis sets. The optimised
      bond length and bond angles are correlated with the X-ray data. The experimental
      wavenumbers were compared with the scaled vibrational frequencies determined by
      DFT methods. The IR and Raman intensities are determined with B3LYP method using
      cc-pVDZ and 6-31G(d,p) basic sets. The total electron density and molecular
      electrostatic potential surfaces of the molecule are constructed by using
      B3LYP/cc-pVDZ method to display electrostatic potential (electron+nuclei)
      distribution. The electronic properties HOMO and LUMO energies were measured.
      Natural bond orbital analysis of O-desmethyltramadol hydrochloride has been
      performed to indicate the presence of intramolecular charge transfer. The (1)H
      and (13)C NMR chemical shifts of the molecule have been anlysed.

PMID- 24316547
TI  - First specifically designed comparative outcome study? Re: Cheng et al, Clin J
      Pain 2012.

PMID- 24316548
TI  - Electrophysiological measures of attention during speech perception predict
      metalinguistic skills in children.
AB  - Event-related potential (ERP) evidence demonstrates that preschool-aged children
      selectively attend to informative moments such as word onsets during speech
      perception. Although this observation indicates a role for attention in language
      processing, it is unclear whether this type of attention is part of basic speech
      perception mechanisms, higher-level language skills, or general cognitive
      abilities. The current study examined these possibilities by measuring ERPs from
      5-year-old children listening to a narrative containing attention probes
      presented before, during, and after word onsets as well as at random control
      times. Children also completed behavioral tests assessing verbal and nonverbal
      skills. Probes presented after word onsets elicited a more negative ERP response
      beginning around 100 ms after probe onset than control probes, indicating
      increased attention to word-initial segments. Crucially, the magnitude of this
      difference was correlated with performance on verbal tasks, but showed no
      relationship to nonverbal measures. More specifically, ERP attention effects were
      most strongly correlated with performance on a complex metalinguistic task
      involving grammaticality judgments. These results demonstrate that effective
      allocation of attention during speech perception supports higher-level,
      controlled language processing in children by allowing them to focus on relevant
      information at individual word and complex sentence levels.

PMID- 24316549
TI  - Assessment of rodent brain activity using combined [(15)O]H2O-PET and BOLD-fMRI.
AB  - The study of brain activation in small animals is of high interest for
      neurological research. In this study, we proposed a protocol to monitor brain
      activation in rats following whisker stimulation using the short half-life PET
      tracer [(15)O]H2O as a marker for cerebral blood flow. This technique enables the
      study of baseline and activation conditions in fast succession within the same
      scanning session. Furthermore, we compared the results obtained from PET imaging
      with additional BOLD-fMRI data acquired in the same animals within the same
      anesthetic session in immediate succession. Although the maximum relative signal
      changes during brain activity observed with PET were substantially higher
      compared to the BOLD-fMRI results, statistical analyses showed that the number of
      activated voxels in PET was lower compared to the fMRI measurements. Furthermore,
      there was a difference in the activation centers in both the shape and location
      between PET and fMRI. The discrepancy in the number of activated voxels could be
      attributed to a lower overall contrast-to-noise ratio of the PET images compared
      to BOLD-fMRI, whereas the difference in the spatial location indicates a more
      fundamental process, involving the different physiological origins of the PET and
      BOLD-fMRI response. This study clearly demonstrates that [(15)O]H2O-PET
      activation studies may be performed in small laboratory animals, and shows the
      complementary nature of studying brain activation using [(15)O]H2O-PET and fMRI. 

PMID- 24316550
TI  - CTLA-4 blockade enhances antitumor immunity of intratumoral injection of immature
      dendritic cells into irradiated tumor in a mouse colon cancer model.
AB  - Dendritic cells (DCs)-based cancer immunotherapy has been used various strategies
      to inhibit immune suppressive mechanisms. CD25 antibodies and cyclophosphamide
      are well-studied immunomodulators through inhibition of regulatory T cells (Treg)
      and a blockade the immune-checkpoint molecule, cytotoxic T-lymphocyte-associated
      protein 4 (CTLA-4) was recently targeted for immunomodulation. We used anti-CTLA
      4 antibody, which is known to induce effective antitumor immunity by facilitating
      tumor-specific T-cell activation and suppressing Treg cells, as useful
      immunomodulator to provide a potentiating effect in the intratumoral injection of
      immature DCs (iDCs) into the irradiated tumor (IR/iDC). Ionizing radiation (IR)
      was applied at a dose of 10 Gy to the tumor on the right thigh of mice. Then,
      iDCs were intratumorally injected into the irradiated tumor. Anti-CTLA-4 antibody
      (100 ug/mouse) was administered intraperitoneally to mice on the same day with
      every iDCs injection. The growth of distant tumors was inhibited by IR/iDC and
      this effect was significantly augmented by combination treatment of anti-CTLA-4
      antibody. Furthermore, the survival rate of tumor-bearing mice improved more by
      the combination treatment of anti-CTLA-4 antibody and IR/iDC compared with other
      groups. It was related to the increased tumor-specific interferon-gamma-secreting
      T cells and CTL activity. Therefore, our results demonstrated that
      immunomodulator such as anti-CTLA-4 antibody enhances antitumor immunity of
      intratumoral injection of iDCs into irradiated tumor and suggested a new strategy
      to get more clinical benefits for cancer treatment. 

PMID- 24316551
TI  - Combining the antimesothelin immunotoxin SS1P with the BH3-mimetic ABT-737
      induces cell death in SS1P-resistant pancreatic cancer cells.
AB  - SS1P is an antimesothelin recombinant immunotoxin (RIT). Pancreatic ductal
      adenocarcinoma (PDAC) cell lines are resistant to SS1P, despite high mesothelin
      expression. The aim of this study is to examine whether combining SS1P and BH3
      mimetic ABT-737 induces cell death in a panel of PDAC cell lines. ABT-737 binds
      and neutralizes several antiapoptotic BCL2 family proteins, but has a low
      affinity for the short-lived MCL1 and BCL2A1. SS1P inhibits protein synthesis,
      which has shown to downregulate MCL1. PDAC cell lines KLM-1, BxPc-3, and Panc
      3.014 were resistant to SS1P or ABT-737 alone. Combining both compounds led to a
      significant increase in cell death. After 48 hours of treatment, cell death was
      observed in 92% of KLM-1, 55% of BxPc-3, and 23% of Panc 3.014 cells. Panc 3.014
      had the highest number of mesothelin-binding sites (92*10(3)), followed by KLM-1
      (58*10(3)) and BxPc-3 (3*10(3)). ABT-737 had no effect on SS1P internalization,
      but enhanced SS1P-induced protein synthesis inhibition significantly in KLM-1, to
      a lesser extent in BxPc-3, and very little in Panc 3.014. SS1P alone or in
      combination with ABT-737 downregulated MCL1 in KLM-1 and BxPc-3, but not in Panc
      3.014. Similar observations were made for BCL2A1, which had the highest levels in
      Panc 3.014. Compared with KLM-1, Panc 3.014, and BxPc-3 also had lower
      proapoptotic BAK and a trend toward higher MCL1. Proapoptotic BAX was similar in
      KLM-1 and BxPc-3, but lower in Panc 3.014. In conclusion, combining SS1P with ABT
      737 overcomes SS1P-resistance in PDAC, although to a variable extent. The
      efficacy of the combination is mainly associated with the RIT-associated
      inhibition of protein synthesis and the ability to downregulate MCL1 and BCL2A1,
      while levels of other key apoptotic proteins may also be important. Our data
      support the combination of an RIT and a BH3-mimetic, and identify factors that
      potentially limit the efficacy of such therapeutic approach.

PMID- 24316552
TI  - A bacterial flagellin in combination with proinflammatory cytokines activates
      human monocyte-derived dendritic cells to generate cytotoxic T lymphocytes having
      increased homing signals to cancer.
AB  - Flagellin, the cognate ligand for toll-like receptor 5, has potent adjuvant
      activity in various vaccines. However, its efficacy in generating dendritic cells
      (DCs) remains contentious. This study assessed how efficaciously Vibrio
      vulnificus FlaB (v-FlaB) could be used in generating a potent DC to induce
      antigen-specific cytotoxic T lymphocytes (CTLs). Mature DCs (mDCs) induced by the
      combination of v-FlaB/TNFalpha/IFNalpha were significantly more potent in
      inducing specific anticancer immune responses compared with the standard DCs that
      were maturated by the conventional cytokine cocktail of TNFalpha/IL-1beta/IL
      6/PGE(2). The potent mDCs produced a higher level of interleukin (IL)-12p70 and
      polarized naive CD4(+) T cells more towards Th1-type cells, markedly increased
      antigen-specific CD8(+) T-cell number and significantly enhanced the induction of
      lytic enzymes in antigen-specific CD8(+) CTLs and sensitized CD3(+) T cells to
      produce higher number of interferon (IFN)gamma-secreting cells. As a result, the
      mDCs produced more potent antigen-specific CTLs against the MART-1 and expressed
      higher levels of homing receptors CCR5 and CXCR3. More importantly, the v
      FlaB/TNFalpha/IFNalpha-DCs generated from melanoma patients produced strong
      autologous CTLs with efficient cytotoxic activities. In conclusion, v-FlaB
      combined with tumor necrosis factor (TNF)alpha and IFNalpha can generate potent
      DCs which produce functionally active CTLs and that may have potential as a
      potent cancer vaccine.

PMID- 24316553
TI  - Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage
      colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy
      in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label
      randomized phase III trial.
AB  - The GOLFIG-2 phase III trial was designed to compare the immunobiological
      activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with
      standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal
      cancer (mCRC) patients. This trial was conceived on the basis of previous
      evidence of antitumor and immunomodulating activity of the GOLFIG regimen in
      mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458
      81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly
      standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85
      mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400
      mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF
      (100 MUg, days 3-7); sc. aldesleukin (0.5 MIU bi-daily, days 8-14 and 17-30)]
      treatments. The study underwent early termination because of poor recruitment in
      the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed
      superiority over FOLFOX in terms of progression-free survival [median 9.23 (95%
      confidence interval (CI), 6.9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months;
      hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0.002] and response rate [66.1%
      (95% CI, 0.41-0.73) vs. 37.0% (95% CI, 0.28-0.59), P=0.002], with a trend to
      longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07
      20.07); HR: 0.79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm
      showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs
      (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T
      lymphocytes, natural killer cells, and a decrease in immunoregulatory
      (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide
      proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable
      option for first-line treatment of mCRC.

PMID- 24316554
TI  - A phase I clinical trial of vaccination with KIF20A-derived peptide in
      combination with gemcitabine for patients with advanced pancreatic cancer.
AB  - KIF20A (RAB6KIFL) belongs to the kinesin superfamily of motor proteins, which
      play critical roles in the trafficking of molecules and organelles during the
      growth of pancreatic cancer. Immunotherapy using a previously identified epitope
      peptide for KIF20A is expected to improve clinical outcomes. A phase I clinical
      trial combining KIF20A-derived peptide with gemcitabine (GEM) was therefore
      conducted among patients with advanced pancreatic cancer who had received prior
      therapy such as chemotherapy and/or radiotherapy. GEM was administered at a dose
      of 1000 mg/m(2) on days 1, 8, and 15 in a 28-day cycle. The KIF20A-derived
      peptide was injected subcutaneously on a weekly basis in a dose-escalation manner
      (doses of 0.5, 1, and 3 mg/body; 3 patients/cohort). Safety and immunologic
      parameters were assessed. No severe adverse effects of grade 3 or higher related
      to KIF20A-derived peptide were observed. Of the 9 patients who completed at least
      one course of treatment, interferon-gamma (IFN-gamma)-producing cells were
      induced in 4 of 9 patients (P2, P3, P6, and P7), and IFN-gamma-producing cells
      were increased in 4 of the 9 patients (P1, P5, P8, and P9). Four of the 9
      patients achieved stable disease. The disease control rate was 44%. The median
      survival time after first vaccination was 173 days and 1-year survival rate was
      11.1%. IFN-gamma-producing cells were induced by the KIF20A-derived peptide
      vaccine at a high rate, even in combination with GEM. These results suggest that
      this combination therapy will be feasible and promising for the treatment of
      advanced pancreatic cancer.

PMID- 24316555
TI  - Association of myeloid-derived suppressor cells and efficacy of cytokine-induced
      killer cell immunotherapy in metastatic renal cell carcinoma patients.
AB  - Metastatic renal cell carcinoma (MRCC) is one of the malignancies that are
      sensitive to immunotherapy. However, the underlying immune inhibitory factors
      such as myeloid-derived suppressor cells (MDSCs) might restrain the efficacy of
      immunotherapy. The present study investigates the clinical efficacy of cytokine
      induced killer (CIK) cell therapy in patients with MRCC and explores whether the
      levels of peripheral MDSCs are associated with the prognosis of patients
      receiving this therapy. Twenty-nine patients with measurable MRCC were treated
      with an adoptive transfer of autologous CIK cells, followed by 5 consecutive days
      of interleukin-2 administration. The tumor response and 1-year survival were
      observed. The proportion of MDSCs in the peripheral blood was detected, and the
      correlation of MDSCs with prognosis was analyzed. Of 29 evaluable patients, no
      complete responses were seen; 4 patients exhibited a partial response (13.8%), 18
      patients displayed stable disease (62.1%), and 7 patients showed progressive
      disease (24.1%). Twenty patients (69.0%) were alive 14.8-41.4 months at the time
      of the last follow-up (median follow-up=20.2 mo). The 1-year survival was 82.8%
      (24/29). Peripheral blood MDSCs were elevated in almost all MRCC patients and
      decreased after CIK-cell infusion. Subgroup analysis indicated that patients with
      a relatively low proportion of MDSCs exhibited prolonged survival. In conclusion,
      our data suggest that transfusion of autologous CIK cells can induce regression
      of MRCC, and MDSCs can serve as a potential marker for the prognosis of patients
      receiving a CIK-based therapy. 

PMID- 24316556
TI  - Immunomodulatory effects of everolimus in a long responsive patient with
      metastatic renal cell carcinoma.
AB  - Everolimus is an inhibitor of mammalian target of rapamycin, approved in patients
      with metastatic renal cell carcinoma. Besides, mammalian target of rapamycin
      inhibition has the ability to modulate T-lymphocyte homeostasis. Here, we report
      the case of a metastatic renal cell carcinoma patient treated with everolimus who
      presented unexpected prolonged tumor response. The monitoring of immune responses
      showed strong antitumor T-cell activation at the time of disease control, whereas
      a profound immunosuppression occurred when tumor progressed. Thus, a change of
      immune functions is associated with everolimus treatment. Our observation
      suggests that everolimus could shape immune responses, which in turn could
      contribute to its efficacy. 

PMID- 24316557
TI  - A phase I trial of bortezomib and interferon-alpha-2b in metastatic melanoma.
AB  - The possibility that cytokine administration could enhance the antitumor effects
      of proteasome inhibition was explored. It was found that coadministration of
      bortezomib and interferon-alpha (IFN-alpha) induced synergistic apoptosis in
      human melanoma cell lines and prolonged survival in a murine model of melanoma. A
      phase I study was conducted to determine the tolerability and the maximum
      tolerated dose of bortezomib when administered in combination with IFN-alpha-2b
      to patients with metastatic melanoma. Patients were treated on a 5-week cycle. In
      week 1 of cycle 1, patients received 5 million U/m(2) IFN-alpha subcutaneously
      thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered
      intravenously weekly along with IFN-alpha thrice weekly. There was a treatment
      break during week 5. After cycle 1, bortezomib was administered in combination
      with IFN-alpha. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6
      mg/m) to cohorts of 3 patients. Sixteen patients were treated (8 women, 8 men;
      median age 59 y). Common grade 3 toxicities included fatigue (5), vomiting (3),
      and diarrhea (3). Grade 4 toxicities included fatigue (3) and lymphopenia (1).
      The maximum tolerated dose for bortezomib was 1.3 mg/m(2). One patient had a
      partial response, and 7 had stable disease. Progression-free survival was 2.5
      months, and overall survival was 10.3 months. Bortezomib administration did not
      augment the ability of IFN-alpha to induce phosphorylation of STAT1 in
      circulating immune cells; however, it did lead to reduced plasma levels of
      proangiogenic cytokines. The combination of bortezomib and IFN-alpha can be
      safely administered to melanoma patients.

PMID- 24316558
TI  - Reversion of erlotinib-acquired resistance twice by chemotherapy: a case report.
AB  - Epidermal growth factor receptor (EGFR) mutations in patients with non-small cell
      lung cancer (NSCLC) usually develop disease progression after a median of 10 to
      14 mo on tyrosine kinase inhibitor (TKI). Several mechanisms of resistance to TKI
      have been described, threonine-methionine substitution at position 790 (T790M),
      mesenchymal-epithelial transition factor (MET) amplification, overexpression of
      hepatocyte growth factor (HGF), upregulation of insulin-like growth factor (IGF)
      receptor signaling, transformation to small cell lung cancer, and so on. A
      variety of different therapeutic approaches aimed at overcoming resistance are
      motivated, irreversible EGFR inhibitors, combination with EGFR targeted
      antibodies, mesenchymal-epithelial transition factor (MET) inhibitors, HGF
      inhibitors, and so forth. Nevertheless, the results were not optimistic. Here we
      report a case of reversion of erlotinib-acquired resistance twice, and had a good
      improvement of outcomes every time. There are some possible reasons for this
      phenomenon. Considering this report, the patients who acquired resistance after
      retreatment of EGFR-TKI, using EGFR-TKI repeatedly may be a choice selectively. 

PMID- 24316559
TI  - Variable range hopping conductivity and spin glass behavior in spin-ladder
      Ba0.6K0.4Fe2Se3 single crystals.
AB  - Ba0.6K0.4Fe2Se3 (BKFS) single crystals were investigated by means of measurements
      of powder x-ray diffraction, temperature-dependent resistivity, anisotropic dc
      magnetization, ac magnetic susceptibility and specific heat. The powder x-ray
      diffraction indicates staggered iron displacements along the ladders with short
      and long Fe-Fe bond lengths (2.64(2) and 2.91(2) A) variation. The resistivity of
      BKFS exhibits variable range hopping behavior with ln(rho) ~ T(-1/2) at low
      temperature. The magnetic susceptibility chi(T) exhibits a sharp cusp at around
      20 K in a zero-field-cooled process. The frequency-dependent ac magnetic
      susceptibility reveals that the cusp feature is attributable to spin glass
      behavior. The anisotropic ac magnetic susceptibility indicates that BKFS is
      probably an anisotropic Heisenberg-like spin glass with its easy magnetization
      plane perpendicular to the chain direction. The specific heat also supports an
      insulating and spin glass ground state. Extended Curie-Weiss behavior above 40 K
      was observed with a reduced effective moment (MU(eff) = 1.66 MU(B)/Fe for H is
      perpendicular to b and MU(eff) = 1.82 MUB/Fe for H is parallel to b) in BKFS,
      which is close to the spin-only magnetism with S=1/2.

PMID- 24316562
TI  - Mobile cloud-computing-based healthcare service by noncontact ECG monitoring.
AB  - Noncontact electrocardiogram (ECG) measurement technique has gained popularity
      these days owing to its noninvasive features and convenience in daily life use.
      This paper presents mobile cloud computing for a healthcare system where a
      noncontact ECG measurement method is employed to capture biomedical signals from
      users. Healthcare service is provided to continuously collect biomedical signals
      from multiple locations. To observe and analyze the ECG signals in real time, a
      mobile device is used as a mobile monitoring terminal. In addition, a
      personalized healthcare assistant is installed on the mobile device; several
      healthcare features such as health status summaries, medication QR code scanning,
      and reminders are integrated into the mobile application. Health data are being
      synchronized into the healthcare cloud computing service (Web server system and
      Web server dataset) to ensure a seamless healthcare monitoring system and anytime
      and anywhere coverage of network connection is available. Together with a Web
      page application, medical data are easily accessed by medical professionals or
      family members. Web page performance evaluation was conducted to ensure minimal
      Web server latency. The system demonstrates better availability of off-site and
      up-to-the-minute patient data, which can help detect health problems early and
      keep elderly patients out of the emergency room, thus providing a better and more
      comprehensive healthcare cloud computing service. 

PMID- 24316564
TI  - Detection of driver drowsiness using wavelet analysis of heart rate variability
      and a support vector machine classifier.
AB  - Driving while fatigued is just as dangerous as drunk driving and may result in
      car accidents. Heart rate variability (HRV) analysis has been studied recently
      for the detection of driver drowsiness. However, the detection reliability has
      been lower than anticipated, because the HRV signals of drivers were always
      regarded as stationary signals. The wavelet transform method is a method for
      analyzing non-stationary signals. The aim of this study is to classify alert and
      drowsy driving events using the wavelet transform of HRV signals over short time
      periods and to compare the classification performance of this method with the
      conventional method that uses fast Fourier transform (FFT)-based features. Based
      on the standard shortest duration for FFT-based short-term HRV evaluation, the
      wavelet decomposition is performed on 2-min HRV samples, as well as 1-min and 3
      min samples for reference purposes. A receiver operation curve (ROC) analysis and
      a support vector machine (SVM) classifier are used for feature selection and
      classification, respectively. The ROC analysis results show that the wavelet
      based method performs better than the FFT-based method regardless of the duration
      of the HRV sample that is used. Finally, based on the real-time requirements for
      driver drowsiness detection, the SVM classifier is trained using eighty FFT and
      wavelet-based features that are extracted from 1-min HRV signals from four
      subjects. The averaged leave-one-out (LOO) classification performance using
      wavelet-based feature is 95% accuracy, 95% sensitivity, and 95% specificity. This
      is better than the FFT-based results that have 68.8% accuracy, 62.5% sensitivity,
      and 75% specificity. In addition, the proposed hardware platform is inexpensive
      and easy-to-use. 

PMID- 24316566
TI  - A novel voice sensor for the detection of speech signals.
AB  - In order to develop a novel voice sensor to detect human voices, the use of
      features which are more robust to noise is an important issue. Voice sensor is
      also called voice activity detection (VAD). Due to that the inherent nature of
      the formant structure only occurred on the speech spectrogram (well-known as
      voiceprint), Wu et al. were the first to use band-spectral entropy (BSE) to
      describe the characteristics of voiceprints. However, the performance of VAD
      based on BSE feature was degraded in colored noise (or voiceprint-like noise)
      environments. In order to solve this problem, we propose the two-dimensional part
      band energy entropy (TD-PBEE) parameter based on two variables: part-band
      partition number upon frequency index and long-term window size upon time index
      to further improve the BSE-based VAD algorithm. The two variables can efficiently
      represent the characteristics of voiceprints on each critical frequency band and
      use long-term information for noisy speech spectrograms, respectively. The TD
      PBEE parameter can be regarded as a PBEE parameter over time. First, the strength
      of voiceprints can be partly enhanced by using four entropies applied to four
      part-bands. We can use the four part-band energy entropies for describing the
      voiceprints in detail. Due to the characteristics of non-stationary for speech
      and various noises, we will then use long-term information processing to refine
      the PBEE, so the voice-like noise can be distinguished from noisy speech through
      the concept of PBEE with long-term information. Our experiments show that the
      proposed feature extraction with the TD-PBEE parameter is quite insensitive to
      background noise. The proposed TD-PBEE-based VAD algorithm is evaluated for four
      types of noises and five signal-to-noise ratio (SNR) levels. We find that the
      accuracy of the proposed TD-PBEE-based VAD algorithm averaged over all noises and
      all SNR levels is better than that of other considered VAD algorithms. 

PMID- 24316568
TI  - Hierarchical recognition scheme for human facial expression recognition systems.
AB  - Over the last decade, human facial expressions recognition (FER) has emerged as
      an important research area. Several factors make FER a challenging research
      problem. These include varying light conditions in training and test images; need
      for automatic and accurate face detection before feature extraction; and high
      similarity among different expressions that makes it difficult to distinguish
      these expressions with a high accuracy. This work implements a hierarchical
      linear discriminant analysis-based facial expressions recognition (HL-FER) system
      to tackle these problems. Unlike the previous systems, the HL-FER uses a pre
      processing step to eliminate light effects, incorporates a new automatic face
      detection scheme, employs methods to extract both global and local features, and
      utilizes a HL-FER to overcome the problem of high similarity among different
      expressions. Unlike most of the previous works that were evaluated using a single
      dataset, the performance of the HL-FER is assessed using three publicly available
      datasets under three different experimental settings: n-fold cross validation
      based on subjects for each dataset separately; n-fold cross validation rule based
      on datasets; and, finally, a last set of experiments to assess the effectiveness
      of each module of the HL-FER separately. Weighted average recognition accuracy of
      98.7% across three different datasets, using three classifiers, indicates the
      success of employing the HL-FER for human FER. 

PMID- 24316569
TI  - Calibrationless parallel magnetic resonance imaging: a joint sparsity model.
AB  - State-of-the-art parallel MRI techniques either explicitly or implicitly require
      certain parameters to be estimated, e.g., the sensitivity map for SENSE, SMASH
      and interpolation weights for GRAPPA, SPIRiT. Thus all these techniques are
      sensitive to the calibration (parameter estimation) stage. In this work, we have
      proposed a parallel MRI technique that does not require any calibration but
      yields reconstruction results that are at par with (or even better than) state-of
      the-art methods in parallel MRI. Our proposed method required solving non-convex
      analysis and synthesis prior joint-sparsity problems. This work also derives the
      algorithms for solving them. Experimental validation was carried out on two
      datasets-eight channel brain and eight channel Shepp-Logan phantom. Two sampling
      methods were used-Variable Density Random sampling and non-Cartesian Radial
      sampling. For the brain data, acceleration factor of 4 was used and for the other
      an acceleration factor of 6 was used. The reconstruction results were
      quantitatively evaluated based on the Normalised Mean Squared Error between the
      reconstructed image and the originals. The qualitative evaluation was based on
      the actual reconstructed images. We compared our work with four state-of-the-art
      parallel imaging techniques; two calibrated methods-CS SENSE and l1SPIRiT and two
      calibration free techniques-Distributed CS and SAKE. Our method yields better
      reconstruction results than all of them. 

PMID- 24316570
TI  - Illumination of the spatial order of intracellular pH by genetically encoded pH
      sensitive sensors.
AB  - Fluorescent proteins have been extensively used for engineering genetically
      encoded sensors that can monitor levels of ions, enzyme activities, redox
      potential, and metabolites. Certain fluorescent proteins possess specific pH
      dependent spectroscopic features, and thus can be used as indicators of
      intracellular pH. Moreover, concatenated pH-sensitive proteins with target
      proteins pin the pH sensors to a definite location within the cell, compartment,
      or tissue. This study provides an overview of the continually expanding family of
      pH-sensitive fluorescent proteins that have become essential tools for studies of
      pH homeostasis and cell physiology. We describe and discuss the design of
      intensity-based and ratiometric pH sensors, their spectral properties and pH
      dependency, as well as their performance. Finally, we illustrate some examples of
      the applications of pH sensors targeted at different subcellular compartments. 

PMID- 24316574
TI  - Satiety responsiveness in toddlerhood predicts energy intake and weight status at
      four years of age.
AB  - The aim of this study was to examine whether maternal-report of child eating
      behaviour at two years predicted self-regulation of energy intake and weight
      status at four years. Using an 'eating in the absence of hunger' paradigm,
      children's energy intake (kJ) from a semi-standardized lunch meal and a
      standardized selection of snacks were measured. Participants were 37 mother-child
      dyads (16 boys, Median child age=4.4years, Inter-quartile range=3.7-4.5years)
      recruited from an existing longitudinal study (NOURISH randomised controlled
      trial). All participants were tested in their own home. Details of maternal
      characteristics, child eating behaviours (at age two years) reported by mothers
      on a validated questionnaire, and measured child height and weight (at age 3.5
      4years) were sourced from existing NOURISH trial data. Correlation and partial
      correlation analyses were used to examine longitudinal relationships. Satiety
      responsiveness and Slowness in eating were inversely associated with energy
      intake of the lunch meal (partial r=-.40, p=.023, and partial r=-.40, p=.023) and
      the former was also negatively associated with BMI-for-age Z score (partial r=
      .42, p=.015). Food responsiveness and Enjoyment of food were not related to
      energy intake or BMI Z score. None of the eating behaviours were significantly
      associated with energy intake of the snacks (i.e., eating in the absence of
      hunger). The small and predominantly 'healthy weight' sample of children may have
      limited the ability to detect some hypothesized effects. Nevertheless, the study
      provides evidence for the predictive validity of two eating behaviours and future
      research with a larger and more diverse sample should be able to better evaluate
      the predictive validity of other children's early eating behaviour styles. 

PMID- 24316571
TI  - Gas chromatography analysis with olfactometric detection (GC-O) as a useful
      methodology for chemical characterization of odorous compounds.
AB  - The gas chromatography-olfactometry (GC-O) technique couples traditional gas
      chromatographic analysis with sensory detection in order to study complex
      mixtures of odorous substances and to identify odor active compounds. The GC-O
      technique is already widely used for the evaluation of food aromas and its
      application in environmental fields is increasing, thus moving the odor emission
      assessment from the solely olfactometric evaluations to the characterization of
      the volatile components responsible for odor nuisance. The aim of this paper is
      to describe the state of the art of gas chromatography-olfactometry methodology,
      considering the different approaches regarding the operational conditions and the
      different methods for evaluating the olfactometric detection of odor compounds.
      The potentials of GC-O are described highlighting the improvements in this
      methodology relative to other conventional approaches used for odor detection,
      such as sensoristic, sensorial and the traditional gas chromatographic methods.
      The paper also provides an examination of the different fields of application of
      the GC-O, principally related to fragrances and food aromas, odor nuisance
      produced by anthropic activities and odorous compounds emitted by materials and
      medical applications. 

PMID- 24316575
TI  - The Vertebrate Genome Annotation browser 10 years on.
AB  - The Vertebrate Genome Annotation (VEGA) database (http://vega.sanger.ac.uk),
      initially designed as a community resource for browsing manual annotation of the
      human genome project, now contains five reference genomes (human, mouse,
      zebrafish, pig and rat). Its introduction pages have been redesigned to enable
      the user to easily navigate between whole genomes and smaller multi-species
      haplotypic regions of interest such as the major histocompatibility complex. The
      VEGA browser is unique in that annotation is updated via the Human And Vertebrate
      Analysis aNd Annotation (HAVANA) update track every 2 weeks, allowing single gene
      updates to be made publicly available to the research community quickly. The user
      can now access different haplotypic subregions more easily, such as those from
      the non-obese diabetic mouse, and display them in a more intuitive way using the
      comparative tools. We also highlight how the user can browse manually annotated
      updated patches from the Genome Reference Consortium (GRC). 

PMID- 24316577
TI  - The NHGRI GWAS Catalog, a curated resource of SNP-trait associations.
AB  - The National Human Genome Research Institute (NHGRI) Catalog of Published Genome
      Wide Association Studies (GWAS) Catalog provides a publicly available manually
      curated collection of published GWAS assaying at least 100,000 single-nucleotide
      polymorphisms (SNPs) and all SNP-trait associations with P <1 * 10(-5). The
      Catalog includes 1751 curated publications of 11 912 SNPs. In addition to the SNP
      trait association data, the Catalog also publishes a quarterly diagram of all SNP
      trait associations mapped to the SNPs' chromosomal locations. The Catalog can be
      accessed via a tabular web interface, via a dynamic visualization on the human
      karyotype, as a downloadable tab-delimited file and as an OWL knowledge base.
      This article presents a number of recent improvements to the Catalog, including
      novel ways for users to interact with the Catalog and changes to the curation
      infrastructure.

PMID- 24316576
TI  - Ensembl 2014.
AB  - Ensembl (http://www.ensembl.org) creates tools and data resources to facilitate
      genomic analysis in chordate species with an emphasis on human, major vertebrate
      model organisms and farm animals. Over the past year we have increased the number
      of species that we support to 77 and expanded our genome browser with a new
      scrollable overview and improved variation and phenotype views. We also report
      updates to our core datasets and improvements to our gene homology relationships
      from the addition of new species. Our REST service has been extended with
      additional support for comparative genomics and ontology information. Finally, we
      provide updated information about our methods for data access and resources for
      user training. 

PMID- 24316578
TI  - RefSeq microbial genomes database: new representation and annotation strategy.
AB  - The source of the microbial genomic sequences in the RefSeq collection is the set
      of primary sequence records submitted to the International Nucleotide Sequence
      Database public archives. These can be accessed through the Entrez search and
      retrieval system at http://www.ncbi.nlm.nih.gov/genome. Next-generation
      sequencing has enabled researchers to perform genomic sequencing at rates that
      were unimaginable in the past. Microbial genomes can now be sequenced in a matter
      of hours, which has led to a significant increase in the number of assembled
      genomes deposited in the public archives. This huge increase in DNA sequence data
      presents new challenges for the annotation, analysis and visualization
      bioinformatics tools. New strategies have been developed for the annotation and
      representation of reference genomes and sequence variations derived from
      population studies and clinical outbreaks. 

PMID- 24316579
TI  - The 2014 Nucleic Acids Research Database Issue and an updated NAR online
      Molecular Biology Database Collection.
AB  - The 2014 Nucleic Acids Research Database Issue includes descriptions of 58 new
      molecular biology databases and recent updates to 123 databases previously
      featured in NAR or other journals. For convenience, the issue is now divided into
      eight sections that reflect major subject categories. Among the highlights of
      this issue are six databases of the transcription factor binding sites in various
      organisms and updates on such popular databases as CAZy, Database of Genomic
      Variants (DGV), dbGaP, DrugBank, KEGG, miRBase, Pfam, Reactome, SEED, TCDB and
      UniProt. There is a strong block of structural databases, which includes, among
      others, the new RNA Bricks database, updates on PDBe, PDBsum, ArchDB, Gene3D,
      ModBase, Nucleic Acid Database and the recently revived iPfam database. An update
      on the NCBI's MMDB describes VAST+, an improved tool for protein structure
      comparison. Two articles highlight the development of the Structural
      Classification of Proteins (SCOP) database: one describes SCOPe, which automates
      assignment of new structures to the existing SCOP hierarchy; the other one
      describes the first version of SCOP2, with its more flexible approach to
      classifying protein structures. This issue also includes a collection of articles
      on bacterial taxonomy and metagenomics, which includes updates on the List of
      Prokaryotic Names with Standing in Nomenclature (LPSN), Ribosomal Database
      Project (RDP), the Silva/LTP project and several new metagenomics resources. The
      NAR online Molecular Biology Database Collection,
      http://www.oxfordjournals.org/nar/database/c/, has been expanded to 1552
      databases. The entire Database Issue is freely available online on the Nucleic
      Acids Research website (http://nar.oxfordjournals.org/). 

PMID- 24316580
TI  - Toxin delivery by the coat protein of an aphid-vectored plant virus provides
      plant resistance to aphids.
AB  - The sap-sucking insects (order Hemiptera), including aphids, planthoppers,
      whiteflies and stink bugs, present one of the greatest challenges for pest
      management in global agriculture. Insect neurotoxins offer an alternative to
      chemical insecticides for controlling these pests, but require delivery into the
      insect hemocoel. Here we use the coat protein of a luteovirus, an aphid-vectored
      plant virus, to deliver a spider-derived, insect-specific toxin that acts within
      the hemocoel. The luteovirid coat protein is sufficient for delivery of fused
      proteins into the hemocoel of pea aphids, Acyrthosiphon pisum, without virion
      assembly. We show that when four aphid pest species-A. pisum, Rhopalosiphum padi,
      Aphis glycines and Myzus persicae-feed on a recombinant coat protein-toxin
      fusion, either in an experimental membrane sachet or in transgenic Arabidopsis
      plants, they experience significant mortality. Aphids fed on these fusion
      proteins showed signs of neurotoxin-induced paralysis. Luteovirid coat protein
      insect neurotoxin fusions represent a promising strategy for transgenic control
      of aphids and potentially other hemipteran pests. 

PMID- 24316581
TI  - Photoperiodic control of FT-like gene ClFT initiates flowering in Chrysanthemum
      lavandulifolium.
AB  - The FLOWERING LOCUS T (FT) gene plays crucial roles in regulating the transition
      from the vegetative phase to the reproductive phase. In this study, we isolated
      an FT homologous gene (denoted as ClFT) from Chrysanthemum lavandulifolium. The
      sequencing analysis indicated that the promoter of the ClFT gene contains many
      elements, such as light response, abscisic acid, drought-inducibility response
      and CIRCADIAN clock elements. The expression patterns of ClFT in different
      tissues/organs at different developmental stages and its responses to different
      photoperiods were observed. ClFT is expressed in all tested organs/tissues, with
      the highest expression level being observed in the leaves of plants with visible
      floral buds under the short day (SD) condition. Next, we studied the rhythmic
      expression of ClFT during different photoperiod treatments and found that the
      level of ClFT increases with additional hours of continuous dark. ClFT
      accumulates when the continuous dark period is 12 h, regardless of the duration
      of light period. The ectopic expression of the ClFT gene in wild type Arabidopsis
      (Col-0) results in early flowering, with high expression levels of endogenous LFY
      and SOC1 being observed in transgenic Arabidopsis. All results indicated that the
      ClFT gene plays an evolutionarily conserved role in promoting flowering in
      inductive short days in C. lavandulifolium and that this gene could serve as a
      vital target for the genetic manipulation of flowering time in chrysanthemums. 

PMID- 24316582
TI  - Assimilative branches and leaves of the desert plant Alhagi sparsifolia Shap.
      possesses a different adaptation mechanism to shade.
AB  - Leaves and assimilative branches are crucial to the life cycle of Alhagi
      sparsifolia Shap. (Fabaceae), which grows in high-irradiance environments and is
      the main vegetation in the forelands of the Taklamakan Desert. This plant has an
      important role in wind protection and sand fixation at the oasis-desert
      transition zone. The morphology, physiology, and photosynthesis of A. sparsifolia
      leaves growing under low-light conditions have been extensively investigated.
      However, whether the plant's assimilative branches adapt similarly to low light
      levels is unclear, as are its specific light adaptation mechanisms. In this
      report, we characterized the biomass allocation, morphology, and chlorophyll a
      fluorescence of leaves and assimilative branches of A. sparsifolia. The results
      indicated that low-light conditions limited the normal growth of A. sparsifolia.
      The fraction of biomass allocated to leaves increased, whereas that to
      assimilative branches decreased. In addition, leaf thickness and assimilative
      branch diameter decreased, resulting in higher specific leaf area, specific
      assimilative branch length, and area for higher light absorbing and higher
      efficiency of light-usage. The assimilative branches and leaves were responded
      oppositely under low-light conditions in that leaves had lower photosystem II
      activity and assimilative branches had higher light-use efficiency to maximize
      light energy absorption for growth of A. sparsifolia. 

PMID- 24316583
TI  - Synthesis and characterization of fluoro-modified polypropylene films for
      inhibition of biofilm formation.
AB  - Surface hydroperoxide-conjugated polypropylene (PP) films were prepared by
      optimal ozonolysis processing of the films. These hydroperoxide-conjugated groups
      were then used as initiators at room temperature for redox graft polymerization
      of the fluoro vinylic monomer 1H,1H-heptaflourobutyl methacrylate (HFBM). The
      ozonolysis process allows, on one hand, for the formation of the desired
      hydroperoxide-conjugated groups while, on the other hand, leads to an undesired
      degradation of the PP. The ozone treatment time was therefore optimized to obtain
      sufficient hydroperoxide groups for graft polymerization, while maintaining the
      mechanical strength of the films, which was barely affected. The resulting PP
      PolyHFBM (PP-PHFBM) films were characterized by methods such as AFM, ATR, TGA,
      contact angle goniometry and XPS. The antibiofilm properties of the PP-PHFBM
      films were evaluated, using two bacterial strains. An 86% inhibition was observed
      for the Gram-negative Escherichia coli, and a 37% inhibition was observed for the
      Gram-positive Listeria. 

PMID- 24316584
TI  - Drug delivery system based on cyclodextrin-naproxen inclusion complex
      incorporated in electrospun polycaprolactone nanofibers.
AB  - In this study, we select naproxen (NAP) as a reference drug and electrospun poly
      (E-caprolactone) (PCL) nanofibers as a fibrous matrix for our drug-delivery
      system. NAP was complexed with beta-cyclodextrin (betaCD) to form inclusion
      complex (NAP-betaCD-IC) and then NAP-betaCD-IC was incorporated into PCL
      nanofibers via electrospinning. The incorporation of NAP without CD-IC into
      electrospun PCL was also carried out for a comparative study. Our aim is to
      analyze the release profiles of NAP from PCL/NAP and PCL/NAP-betaCD-IC nanofibers
      and we investigate the effect of CD-IC on the release behavior of NAP from the
      nanofibrous PCL matrix. The characterization of NAP-betaCD-IC and the presence of
      CD-IC in PCL/NAP-betaCD-IC nanofibers were studied by FTIR, XRD, TGA, NMR and
      SEM. The SEM imaging of the electrospun PCL/NAP and PCL/NAP-betaCD-IC nanofibers
      reveal that the average fiber diameter of these nanofibers is around 300nm, in
      addition, the aggregates of CD-IC in PCL/NAP-betaCD-IC nanofibers is observed.
      The release study of NAP in buffer solution elucidate that the PCL/NAP-betaCD-IC
      nanofibers have higher release amount of NAP than the PCL/NAP nanofibers due to
      the solubility enhancement of NAP by CD-IC. 

PMID- 24316585
TI  - Multivariate analysis of physicochemical characteristics of lipid based
      nanoemulsifying cilostazol--quality by design.
AB  - Simultaneous analysis of the effect of multiple formulation ingredients on the
      critical physico-chemical properties of lipid based nanoemulsifying cilostazol
      was studied using integrated quality by design approach. Cilostazol is a poorly
      soluble drug belonging to class II of the biopharmaceutics classification system.
      To improve the solubility and in turn bioavailability of cilostazol, a lipid
      based nanoemulsifying cilostazol was developed. Self nanoemulsifying system
      comprising of Capmul MCM (oily solubilizer), Tween 80 (surfactant); and
      Transcutol HP (cosolvent) was developed. A 2(3) full factorial experimental
      design was employed to optimize simultaneously the effect of levels of these
      three components on physico-chemical responses (viz. globule size, span, zeta
      potential, solubility, and dissolution efficiency at 30 min) of nanoemulsifying
      cilostazol. Graphical analysis using Pareto charts and Bayesian analysis along
      with mathematical modelling of the results allowed the identification and
      quantification of the formulation variables active on the selected responses. A
      polynomial equation fitted to the data was used to predict the composition with
      optimum responses. The optimum formulation was a mixture of Capmul MCM, Tween 80
      and Transcutol HP; 3:5:5 parts by weight. Optimized composition on dilution with
      water showed globule size; 215.2 nm with a span of 0.42. The nanoemulsifying
      formulation showed equilibrium solubility and dissolution efficiency; 9.82 mg/ml
      and 83.3% respectively, indicating significant improvement in comparison to
      pristine cilostazol. Interaction between oil and the cosolvent significantly
      affected the globule size and the span of the resultant nanoemulsion. Zeta
      potential was independent of selected formulation variables. The optimized
      formulation was adsorbed onto Neusilin US2 without affecting nanoemusifying
      ability of lipid based cilostazol composition.

PMID- 24316588
TI  - Attitudes towards individuals with disabilities as measured by the implicit
      association test: a literature review.
AB  - Research investigating attitudes towards individuals with disabilities has
      largely focused on self-reported explicit attitudes. Given that factors such as
      social desirability may influence explicit attitudes, researchers have developed
      tools which instead assess less consciously controllable implicit attitudes.
      Considering research on implicit attitudes thus seems pertinent. A review of
      studies measuring implicit attitudes towards individuals with physical
      disabilities (visual, motor or hearing) or intellectual disabilities via the
      Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) was carried
      out. Systematic searches of PsycINFO, CINAHL, EMBASE, ERIC, MEDLINE, PUBMED,
      Scopus and Web of Science databases identified relevant articles published
      between January 2000 and September 2012. Seventeen articles (reporting on 18
      studies that employed the IAT) were identified. These investigated implicit
      attitudes towards individuals with; physical disabilities (N=13), intellectual
      disabilities (N=3), both physical and intellectual disabilities (N=1), and
      'unspecified disabilities' (N=1). Across all studies, moderate to strong negative
      implicit attitudes were found and there was little to no association between
      explicit and implicit attitudes. Individuals' beliefs about the controllability
      of their future, sensitivity to the concept of disease, and contact with
      individuals with disabilities appear to be associated with implicit attitudes. A
      consistent pattern of moderate to strong negative implicit attitudes towards
      individuals with disabilities was evident. These studies provide a starting
      point, but methodological issues related to sampling and the employed IATs limit
      the generalizability of these results. Further research investigating implicit
      attitudes towards specific disability types, with a wider subject pool are
      necessary as well as further investigation of factors that contribute to these
      attitudes. 

PMID- 24316586
TI  - Sensing the dynamics of oxidative stress using enhanced absorption in protein
      loaded random media.
AB  - Reactive oxygen species play a key role in cell signalling and oxidative stress
      mechanisms, therefore, sensing their production by living organisms is of
      fundamental interest. Here we describe a novel biosensing method for
      extracellular detection of endogenous hydrogen peroxide (H2O2). The method is
      based on the enhancement of the optical absorption spectrum of the hemoprotein
      cytochrome c when loaded into a highly scattering random medium. Such a
      configuration enables, in contrast to existing techniques, non-invasive and
      dynamic detection of the oxidation of cyt c in the presence of H2O2 with
      unprecedented sensitivity. Dynamic information on the modification of the cell
      oxidative status of Chlamydomonas reinhardtii, an aquatic green algae, was
      obtained under oxidative stress conditions induced by the presence of trace
      concentrations of Cd(II). Furthermore, the dynamics of H2O2 production was
      investigated under different lighting conditions confirming the impact of Cd(II)
      on the photosynthetic activity of those phytoplanktonic cells. 

PMID- 24316589
TI  - Hand function and its prognostic factors of very low birth weight preterm
      children up to a corrected age of 24 months.
AB  - A delay in functional hand performance broadly affects a child's successful
      participation in daily activities as well as later academic performance. Despite
      its high prevalence, hand function has received much less attention than other
      developmental domains, especially for young children. The aims of this study,
      therefore, were to examine hand function in preterm children up to a corrected
      age of 24 months; to establish predictive models for estimating preterm
      children's hand function; and to identify the contribution of early neuromotor
      assessments. This study included 230 preterm children (69, 76, and 85 children at
      corrected ages of 6-, 12-, and 24-months, respectively) who were recruited from
      the database of the preemie follow-up clinic at the National Cheng Kung
      University Hospital in Tainan, Taiwan. Hand function was evaluated using the
      Peabody Developmental Motor Scales II. Demographic information, birth history,
      and developmental documents were obtained from the medical records of routine
      preemie clinic follow-ups. Approximately half of healthy preterm children
      demonstrate hand function deficits at 12 and 24 months of corrected age. The
      Neonatal Medical Index, representing an infant's history of medical complication,
      was the best predictor of hand function at 12 and 24 months of corrected age. The
      social factor, represented by maternal educational year, was found to have
      influence on hand function only in preterm children at corrected age of 24 months
      old. Finally, early neuromotor performance demonstrated significant
      predictability of later hand function that supports the importance of continuous
      follow-up examinations in children with a history of prematurity. An
      understanding of a preterm child's early hand function as well as how its risk
      factors evolve helps clinicians both target children who might benefit from early
      intervention and ensure that children reach their full developmental potential. 

PMID- 24316590
TI  - Elevated granzyme M-expressing lymphocytes during cytomegalovirus latency and
      reactivation after allogeneic stem cell transplantation.
AB  - Human cytomegalovirus (HCMV) reactivation can cause serious complications in
      allogeneic stem cell transplantation (SCT) patients. HCMV is controlled by
      cytotoxic lymphocytes that release antiviral granzymes. Recently, we have
      demonstrated that granzyme M (GrM) inhibits HCMV replication in vitro, however
      the physiological role of GrM and its cellular distribution during HCMV infection
      remains unknown. Here, we examined GrM expression in lymphocyte populations
      during HCMV infection. The percentage of GrM-expressing effector-memory CD4(+) T
      cells was higher in HCMV latently-infected healthy individuals compared to that
      of uninfected individuals. SCT recipients had higher percentages of GrM
      expressing CD4(+) T, CD8(+) T, gammadeltaT, and NKT cells. Despite lower total T
      cell numbers, HCMV reactivation in SCT patients specifically associated with
      higher percentages of GrM-expressing CD4(+) (total and central-memory) T-cells.
      GrM was elevated in plasma during HCMV reactivation, pointing to extracellular
      perforin-independent functions of GrM. We conclude that GrM may be important in
      regulating HCMV latency and reactivation in SCT patients. 

PMID- 24316591
TI  - Anti-apoptotic roles for the mutant p53R248Q through suppression of p53-regulated
      apoptosis-inducing protein 1 in the RA-derived fibroblast-like synoviocyte cell
      line MH7A.
AB  - We previously reported that somatic mutations in the p53 gene accumulated at a
      higher frequency in AID(activation induced cytidine deaminase)(+) RA-FLS, which
      may result in the malfunction of p53, causing the tumor-like properties of RA
      FLS. Among the p53 mutations identified from 3 sources of AID(+) RA-FLS, we
      focused on the p53R248Q mutation because it was reported to enhance the
      invasiveness of lung cancer cells and to have dominant-negative activity for pro
      apoptotic molecules. We obtained cDNA encoding the p53R248Q mutant and introduced
      it into the MH7A RA-FLS cell line. P53R248Q dramatically suppressed the
      expression of the pro-apoptotic molecule p53AIP1 even under oxidative stress,
      which normally upregulates p53AIP1, leading to apoptosis. Moreover,
      overexpression of p53AIP1 increased apoptosis, whereas p53AIP1 knockdown rescued
      the cells from apoptosis. Together, these studies indicate the critical role of
      p53AIP1 under DNA damaging stresses for cell fate determination in RA-FLS
      containing the p53R248Q mutation. 

PMID- 24316593
TI  - Timescales of water transport in viscous aerosol: measurements on sub-micron
      particles and dependence on conditioning history.
AB  - Evaporation studies of single aqueous sucrose aerosol particles as a function of
      relative humidity (RH) are presented for coarse and fine mode particles down into
      the submicron size range (600 nm < r < 3.0 MUm). These sucrose particles serve as
      a proxy for biogenic secondary organic aerosols that have been shown to exist,
      under ambient conditions, in an ultraviscous glassy state, which can affect the
      kinetics of water mass transport within the bulk phase and hinder particle
      response to changes in the gas phase water content. A counter-propagating Bessel
      beams (CPBBs) optical trapping setup is employed to monitor the real-time change
      in the particle radius with RH decreasing from 75% to 5%. The slow-down of the
      size change upon each RH step and the deviation from the theoretical equilibrium
      hygroscopic growth curve indicate the onset of glassy behavior in the RH range of
      10-40%. Size-dependent effects were not observed within the uncertainty of the
      measurements. The influence of the drying time below the glass transition RH on
      the timescale of subsequent water condensation and re-equilibration for sucrose
      particles is explored by optical tweezers measurements of micron-sized particles
      (3 MUm < r < 6 MUm). The timescale for water condensation and re-equilibration is
      shown to increase with increasing drying time, i.e. the time over which a viscous
      particle is dried below 5% RH. These studies demonstrate the importance of the
      history of the particle conditioning on subsequent water condensation and re
      equilibration dynamics of ultraviscous and glassy aerosol particles. 

PMID- 24316592
TI  - Up-regulation of microRNA-210 induces immune dysfunction via targeting FOXP3 in
      CD4(+) T cells of psoriasis vulgaris.
AB  - Psoriasis vulgaris (PV) is a chronic inflammatory and T cell-mediated autoimmune
      skin disease. An immune dysfunction that is manifested by abnormally activated T
      cells and defective regulatory T (Treg) cells may play an important role in the
      pathogenesis of PV. However, the precise mechanism of the immune dysfunction in
      PV patients still remains unclear. In this study, we found that miR-210
      expression is increased significantly in CD4(+) T cells from patients with PV and
      confirmed that FOXP3 is a target gene of miR-210. We also found that
      overexpression of miR-210 inhibits FOXP3 expression and impairs the
      immunosuppressive functions of Treg cells in CD4(+) T cells from healthy
      controls. In contrast, inhibition of miR-210 increases FOXP3 expression and
      reverses the immune dysfunction in CD4(+) T cells from patients with PV. Our data
      demonstrates that increased miR-210 induces immune dysfunction via by FOXP3 in
      CD4(+) T cells from patients with PV. 

PMID- 24316594
TI  - Need for prospective cohort studies to establish human gut microbiome
      contributions to disease risk.

PMID- 24316597
TI  - Honing the health message on BRCA mutations.

PMID- 24316595
TI  - Human gut microbiome and risk for colorectal cancer.
AB  - We tested the hypothesis that an altered community of gut microbes is associated
      with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94
      control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by
      universal primers, sequenced by 454 FLX technology, and aligned for taxonomic
      classification to microbial genomes using the QIIME pipeline. Taxonomic
      differences were confirmed with quantitative polymerase chain reaction and
      adjusted for false discovery rate. All statistical tests were two-sided. From
      794217 16S rRNA gene sequences, we found that CRC case subjects had decreased
      overall microbial community diversity (P = .02). In taxonomy-based analyses,
      lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of
      Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI]
      = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found
      in case subjects compared with control subjects. Because of the potentially
      modifiable nature of the gut bacteria, our findings may have implications for CRC
      prevention. 

PMID- 24316598
TI  - No clear link between passive smoking and lung cancer.

PMID- 24316600
TI  - Racial and ethnic differences in use of mammography between Medicare Advantage
      and traditional Medicare.
AB  - BACKGROUND: Breast cancer is a leading cause of mortality for women in all
      racial/ethnic groups. We compared use of mammography by race/ethnicity in
      Medicare health maintenance organizations (HMOs), preferred provider
      organizations (PPOs), and traditional Medicare. METHODS: We matched 495 836 women
      in HMOs and 81 480 women in PPOs who were aged 65 to 69 years during 2009 to
      women enrolled in traditional Medicare by race/ethnicity, Medicaid eligibility
      status, and geographic area. We identified mammography use from the Healthcare
      Effectiveness Data and Information Set for Medicare HMOs and PPOs and from claims
      data for traditional Medicare with the same specifications. We then compared
      racial/ethnic differences in rates of mammography in HMOs and PPOs to matched
      populations in traditional Medicare and estimated differences with z tests. All
      statistical tests were two-sided. RESULTS: Relative to matched white women,
      mammography rates were statistically significantly higher for black, Hispanic,
      and Asian/Pacific Islander women in HMOs (6.1, 5.4, and 0.9 percentage points,
      respectively; all P <= .003) and statistically significantly lower for all three
      groups in traditional Medicare (3.3, 7.4, and 7.7 percentage points,
      respectively; all P < .001). Similar improvements in mammography rates also were
      observed in PPOs among all minority groups relative to traditional Medicare.
      CONCLUSIONS: Higher rates of mammography in HMOs and PPOs were associated with a
      reversal of racial and ethnic differences observed in traditional Medicare. These
      differences may be related to lower patient cost-sharing and better systems to
      promote preventive services in managed care plans, as well as unmeasured
      characteristics or beliefs of minority women who enroll in these health plans
      relative to those in traditional Medicare.

PMID- 24316601
TI  - The languages of science in cancer nursing research.

PMID- 24316603
TI  - Facilitating social support: member-leader communication in a breast cancer
      support group.
AB  - BACKGROUND: Early detection and treatment have resulted in more women surviving
      breast cancer; increased survivorship has also increased the need for breast
      cancer support groups (BCSG). The ostensible goal of such groups is to provide
      support for the physical and emotional stressors that cancer survivors face, as
      well as provide information on coping and treatment options. OBJECTIVE: Although
      scholars have examined the effects of support groups on their group members, the
      examination of group facilitator messages has been largely neglected. The goal of
      this study was to extend theory on group leader behavior, specifically
      investigating how member-leader messages create social support in support groups.
      METHODS: The transcribed conversations of weekly meetings of a BCSG were examined
      using Interaction Process Analysis to discover how the member-leader facilitated
      the group's enactment and management of social support. RESULTS: Across the
      meetings, task talk dominated (primarily statements of orientation or
      information). Furthermore, analysis of interaction sequences between the support
      group facilitator and other members revealed 2 broad categories of task-oriented
      facilitation techniques (changing the focus, clarification) and 1 category of
      socioemotional facilitation techniques (showing support). CONCLUSIONS: Support
      group facilitators need the ability to facilitate both task and relational
      aspects of social support. IMPLICATIONS FOR PRACTICE: Facilitator behaviors were
      highlighted as being instrumental to the creation of social support. The results
      from this study indicate that the ability to change the focus of interaction, to
      provide and require clarification on complex issues, and to show support through
      relational messages is needed in facilitator training.

PMID- 24316605
TI  - A surge in anti-dsDNA titer predicts a severe lupus flare within six months.
AB  - OBJECTIVE: Rising anti-double-stranded (ds) DNA titers have been shown by some,
      but not all, studies to be predictive of disease flares in systemic lupus
      erythematosus (SLE). We hypothesized that a rapid and substantial rise in anti
      dsDNA titer (anti-dsDNA surge) would be a good predictor of a clinically
      important SLE flare. METHODS: A matched case-control study was conducted in an
      academic rheumatology practice setting. Our primary endpoint was the occurrence
      of a severe SELENA-SLEDAI (SS) flare within six months of an anti-dsDNA surge,
      and secondary endpoints were mild/moderate SS flares, as well as BILAG A and B
      renal flares. Cases were identified as those patients whose disease course
      included a surge of anti-dsDNA, defined as an increase of anti-dsDNA titer by the
      Crithidia luciliae immunofluorescence (CLIF) assay from 0 to 3+/4+, or from 1+ to
      4+, within a period of less than 12 months. The date of the anti-dsDNA surge was
      defined as Day 0. Two control SLE patients were identified for each case and were
      matched for age, sex, race, and visit date closest to case Day 0, but without an
      anti-dsDNA surge. Logistic regression models were used to detect associations
      between anti-dsDNA surges and severe SS flares. RESULT: A higher proportion of
      cases, compared to controls, experienced a severe SS flare within six months of
      Day 0 (OR 6.3 (95% confidence intervals 2.0-19.9), p = 0.02). Associations with
      all flares and hospitalizations for flares were also observed. However, an anti
      dsDNA surge was not predictive of a renal flare. CONCLUSION: An anti-dsDNA surge
      predicts the subsequent development of a severe SS flare within six months.
      Physicians should closely monitor such patients and treat promptly at the first
      sign of clinical activity.

PMID- 24316604
TI  - Different assay conditions for detecting the production and release of heat
      labile and heat-stable toxins in enterotoxigenic Escherichia coli isolates.
AB  - Enterotoxigenic Escherichia coli (ETEC) produce heat-labile (LT) and/or heat
      stable enterotoxins (ST). Despite that, the mechanism of action of both toxins
      are well known, there is great controversy in the literature concerning the in
      vitro production and release of LT and, for ST, no major concerns have been
      discussed. Furthermore, the majority of published papers describe the use of only
      one or a few ETEC isolates to define the production and release of these toxins,
      which hinders the detection of ETEC by phenotypic approaches. Thus, the present
      study was undertaken to obtain a better understanding of ST and LT toxin
      production and release under laboratory conditions. Accordingly, a collection of
      90 LT-, ST-, and ST/LT-producing ETEC isolates was used to determine a protocol
      for toxin production and release aimed at ETEC detection. For this, we used
      previously raised anti-LT antibodies and the anti-ST monoclonal and polyclonal
      antibodies described herein. The presence of bile salts and the use of certain
      antibiotics improved ETEC toxin production/release. Triton X-100, as chemical
      treatment, proved to be an alternative method for toxin release. Consequently, a
      common protocol that can increase the production and release of LT and ST toxins
      could facilitate and enhance the sensitivity of diagnostic tests for ETEC using
      the raised and described antibodies in the present work. 

PMID- 24316606
TI  - The effects of pre- and postoperative fibrinogen levels on blood loss after
      cardiac surgery: a systematic review and meta-analysis.
AB  - OBJECTIVES: Fibrinogen concentrate is increasingly used in cardiac surgery when
      bleeding is anticipated or ongoing. Since randomized clinical studies to support
      this are lacking, it is relevant to know whether lower fibrinogen levels are
      associated with excessive bleeding. We performed a systematic review and meta
      analysis to define the association between fibrinogen levels and blood loss after
      cardiac surgery. METHODS: A database search (January 2013) was performed on
      publications assessing the association between pre- and postoperative fibrinogen
      levels and postoperative blood loss in adult patients undergoing cardiac surgery.
      Cohort studies and case-control studies were eligible for inclusion. The main
      outcome was the pooled correlation coefficient, calculated via Fisher's Z
      transformation scale, in a random-effects meta-analysis model stratified for the
      time point at which fibrinogen was measured. RESULTS: A total of 20 studies were
      included. The pooled correlation coefficient of studies (n = 9) concerning
      preoperative fibrinogen levels and postoperative blood loss was -0.40 (95%
      confidence interval: -0.58, -0.18), pointing towards more blood loss in patients
      with lower preoperative fibrinogen levels. Among papers (n = 16) reporting on
      postoperative fibrinogen levels and postoperative blood loss, the pooled
      correlation coefficient was -0.23 (95% confidence interval: -0.29, -0.16).
      CONCLUSIONS: Our meta-analysis indicated a significant but weak-to-moderate
      correlation between pre- and postoperative fibrinogen levels and postoperative
      blood loss in cardiac surgery. This moderate association calls for appropriate
      clinical studies on whether fibrinogen supplementation will decrease
      postoperative blood loss.

PMID- 24316610
TI  - Patient engagement: essential partnerships to improve outcomes.

PMID- 24316607
TI  - Mesoporous silica nanoparticle-based substrates for cell directed delivery of
      Notch signalling modulators to control myoblast differentiation.
AB  - Biochemical cues are critical to control stem cell function and can be utilized
      to develop smart biomaterials for stem cell engineering. The challenge is to
      deliver these cues in a restricted manner with spatial and temporal control. Here
      we have developed bilayer films of mesoporous silica nanoparticles for delayed
      cellular delivery of Notch modulators to promote muscle stem cell
      differentiation. We demonstrate that drug-loaded particles are internalized from
      the particle-covered surface, which allows for direct delivery of the drug into
      the cell and a delayed and confined drug release. Substrates of particles loaded
      with gamma-secretase-inhibitors, which block the Notch signalling pathway,
      promoted efficient differentiation of myoblasts. The particle substrates were
      fully biocompatible and did not interfere with the inherent differentiation
      process. We further demonstrate that impregnating commercially available,
      biocompatible polymer scaffolds with MSNs allows for a free standing substrate
      for cell directed drug delivery. 

PMID- 24316611
TI  - Building joint commission continuous readiness in partnership with nursing
      students.
AB  - A partnership between an academic medical center and a college of nursing has
      proven to be an equally beneficial opportunity for continuous readiness for The
      Joint Commission. Nursing students learn the principles of regulatory compliance
      and accreditation through simulated surveys in their leadership and management
      course. The medical center receives continuous feedback and achieves survey
      readiness and fluency with better-prepared new graduates. 

PMID- 24316612
TI  - The influence of emerging administrative scientists: an interview with Dr Maja
      Djukic. Interview by Jeffrey M. Adams.
AB  - This department highlights emerging nursing leaders and scientists who have
      demonstrated great promise and findings in advancing innovation and patient care
      leadership in practice, policy, research, education and theory. This interview
      profiles Maja Djukic, PhD, RN, assistant professor, New York University College
      of Nursing. 

PMID- 24316614
TI  - Sleep deprivation and error in nurses who work the night shift.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      sleep deprivation and occupational and patient care errors among staff nurses who
      work the night shift. BACKGROUND: Whereas the aviation and trucking industries
      report that sleep deprivation increases errors, few studies have examined sleep
      deprivation association with occupational and patient care errors among nurses.
      METHODS: A cross-sectional correlational design was used to evaluate
      relationships between sleep deprivation and occupational and patient care errors
      in 289 hospital night shift nurses. RESULTS: More than half (56%) of the sample
      reported being sleep deprived. Sleep-deprived nurses made more patient care
      errors. Testing for associations with occupational errors was not feasible
      because of the low number of occupational errors reported. CONCLUSION:
      Interventions to increase the quality and quantity of sleep among hospital night
      shift nurses are needed. Improved sleep among night shift nurses will reduce the
      impact of sleep deprivation on patient care errors.

PMID- 24316613
TI  - Understanding the role of the professional practice environment on quality of
      care in Magnet(r) and non-Magnet hospitals.
AB  - OBJECTIVE: The aim of this study was to explore the relationship between Magnet
      Recognition(r) and nurse-reported quality of care. BACKGROUND: Magnet(r)
      hospitals are recognized for nursing excellence and quality patient outcomes;
      however, few studies have explored contributing factors for these superior
      outcomes. METHODS: This was a secondary analysis of linked nurse survey data,
      hospital administrative data, and a listing of American Nurses Credentialing
      Center Magnet hospitals. Multivariate regressions were modeled before and after
      propensity score matching to assess the relationship between Magnet status and
      quality of care. A mediation model assessed the indirect effect of the
      professional practice environment on quality of care. RESULTS: Nurse-reported
      quality of care was significantly associated with Magnet Recognition after
      matching. The professional practice environment mediates the relationship between
      Magnet status and quality of care. CONCLUSION: A prominent feature of Magnet
      hospitals, a professional practice environment that is supportive of nursing,
      plays a role in explaining why Magnet hospitals have better nurse-reported
      quality of care.

PMID- 24316615
TI  - How hospital leaders contribute to patient safety through the development of
      trust.
AB  - OBJECTIVE: The aim of this study was to explore the associations between hospital
      management support for patient safety, registered nurses' trust in hospital
      management, and their overall perception of patient safety, considering aspects
      of safety communication as possible mediating variables. BACKGROUND: Limited
      research exists regarding how key elements of a patient safety culture, that is,
      leadership, safety communication, and trust, are interrelated. METHODS: This
      study used cross-sectional nurse survey data from 1,633 registered nurses working
      in 35 acute care hospitals participating in the Swiss arm of the RN4CAST (Nurse
      Forecasting in Europe) study. RESULTS: A path analysis revealed that the indirect
      associations between "management support for patient safety" and "overall
      perception of patient safety" were more prominent than the direct association.
      CONCLUSION: Our findings confirm that safety communication plays a partially
      mediating role between "management support for patient safety" and nursing
      professionals' assessments of patient safety. This suggests that hospital leader
      unit exchanges might improve patient safety.

PMID- 24316616
TI  - Addressing hospital-acquired pressure ulcers: patient care managers enhancing
      outcomes at the point of service.
AB  - An innovative leadership training program for patient care managers (PCMs) aimed
      at improving the management of operational failures was conducted at a large
      metropolitan hospital center. The program focused on developing and enhancing the
      transformational leadership skills of PCMs by improving their ability to manage
      operational failures in general and, in this case, hospital-acquired pressure
      ulcers. The PCMs received 8 weeks of intense training using the Toyota Production
      System process improvement approach, along with executive coaching. Compared with
      the control group, the gains made by the intervention group were statistically
      significant. 

PMID- 24316617
TI  - A nurse manager succession planning model with associated empirical outcomes.
AB  - OBJECTIVE: Perceptions of leadership and management competency after a formal
      nurse manager succession planning program were evaluated. BACKGROUND: A lack of
      strategic workforce planning and development of a leadership pipeline contributes
      to a predicted nurse manager shortage. To meet the anticipated needs for future
      leadership, evidence-based action is critical. METHODS: A quasi-experimental
      mixed-methods, 1-group pretest/posttest research design was used. Nurses working
      in an acute care hospital were recruited for the study and selected using an
      objective evaluative process. RESULTS: Participant perceptions regarding their
      leadership and management competencies significantly increased after the
      leadership program. Program evaluations confirmed that participants found the
      program beneficial. One year after program completion, 100% of the program
      participants have been retained at the organization and 73% had transitioned to
      leadership roles. CONCLUSION: Succession planning and leadership development
      serve as beneficial and strategic mechanisms for identifying and developing high
      potential individuals for leadership positions, contributing toward the future
      nursing leadership pipeline.

PMID- 24316618
TI  - Improving outcomes through the proper implementation of acute care nurse
      practitioners.
AB  - The Value-Based Purchasing Program is forcing hospitals to improve outcomes and
      decrease costs. This has led to recognition of new care models to improve
      outcomes and reimbursement. One model is the application of an acute care nurse
      practitioner (ACNP) into the hospital setting. Model success is dependent on
      proper implementation to create a synergistic relationship with the organization,
      ACNP, and patient to improve the quality of care and decrease costs for the
      hospital. 

PMID- 24316619
TI  - Assessing the professional development needs of experienced nurse executive
      leaders.
AB  - OBJECTIVE: The objective of this study was to identify the professional
      development topics that senior nurse leaders believe are important to their
      advancement and success. BACKGROUND: Senior/experienced nurse leaders at the
      executive level are able to influence the work environment of nurses and
      institutional and health policy. Their development needs are likely to reflect
      this and other contemporary healthcare issues and may be different from middle
      and frontline managers. A systematic way of assessing professional development
      needs for these nurse leaders is needed. METHODS: A descriptive study using an
      online survey was distributed to a convenience sample of nurse leaders who were
      members of the Association of California Nurse Leaders (ACNL) or have
      participated in an ACNL program. RESULTS: Visionary leadership, leading
      complexity, and effective teams were the highest ranked leadership topics.
      Leading change, advancing health: The future of nursing, healthy work
      environments, and healthcare reform were also highly ranked topics. CONCLUSIONS:
      Executive-level nurse leaders are important to nurse retention, effective work
      environments, and leading change. Regular assessment and attention to the
      distinct professional development needs of executive-level nurse leaders are a
      valuable human capital investment.

PMID- 24316620
TI  - The INN crowd.

PMID- 24316621
TI  - Phase 3 data for PCSK9 inhibitor wows.

PMID- 24316622
TI  - Appetite for cheaper biologics spreads across the map.

PMID- 24316625
TI  - Biocon's first-in-class anti-CD6 mAb reaches the market.

PMID- 24316627
TI  - First-in-class guanylate cyclase stimulator approved for PAH.

PMID- 24316629
TI  - JDRF teams with VC PureTech to promote startups.

PMID- 24316631
TI  - GSK plows ahead with EMA malaria vaccine submission.

PMID- 24316634
TI  - Burning bright.

PMID- 24316635
TI  - Do you really want to be a biotech board member?

PMID- 24316636
TI  - Startups on the menu: Archimedes.

PMID- 24316637
TI  - Just the facts, please.

PMID- 24316638
TI  - Reply to Just the facts, please.

PMID- 24316639
TI  - Science-based risk assessment requires careful evaluation of all studies.

PMID- 24316640
TI  - Reply to Science-based risk assessment requires careful evaluation of all
      studies.

PMID- 24316641
TI  - Rational drug repositioning by medical genetics.

PMID- 24316642
TI  - Reply to Rational drug repositioning by medical genetics.

PMID- 24316643
TI  - Vaccine delivery with microneedle skin patches in nonhuman primates.

PMID- 24316644
TI  - Transparency tools in gene patenting for informing policy and practice.

PMID- 24316646
TI  - Mining the ultimate phenome repository.

PMID- 24316647
TI  - Epigenome editing.

PMID- 24316648
TI  - Genome assembly and haplotyping with Hi-C.

PMID- 24316655
TI  - Fixing the broken graduate education experience.

PMID- 24316657
TI  - In vitro DNA binding studies of the sweetening agent saccharin and its copper(II)
      and zinc(II) complexes.
AB  - The interactions of fish sperm DNA (FS-DNA) with the sodium salt of sweetener
      saccharin (sacH) and its copper and zinc complexes, namely [M(sac)2(H2O)4].2H2O
      (M=Cu(II) or Zn(II)) were studied by using UV-Vis titration, fluorometric
      competition, thermal denaturation, viscosity and gel electrophoresis
      measurements. The intrinsic binding constants (Kb) obtained from absorption
      titrations were estimated to be 2.86 (+/-0.06)*10(4)M(-1) for Na(sac), 6.67 (+/
      0.12)*10(4)M(-1) for Cu-sac and 4.01 (+/-0.08)*10(4)M(-1) for Zn-sac. The Cu-sac
      complex binds to FS-DNA via intercalation with a KA value of 50.12 (+/
      0.22)*10(4)M(-1) as evidenced by competitive binding studies with ethidium
      bromide. Moreover, competition experiments with Hoechst 33258 are indicative of a
      groove binding mode of Na(sac) and Zn-sac with binding constants of 3.13 (+/
      0.16)*10(4)M(-1) and 5.25 (+/-0.22)*10(4)M(-1), respectively. The spectroscopic
      measurements indicate a moderate DNA binding affinity of Na(sac) and its metal
      complexes. The suggested binding modes are further confirmed by the thermal
      denaturation and viscosity measurements. In addition, Cu-sac and Zn-sac show weak
      ability to damage to pBR322 supercoiled plasmid DNA. 

PMID- 24316658
TI  - Enhanced bactericidal action of SnO2 nanostructures having different morphologies
      under visible light: influence of surfactant.
AB  - The practical use of visible-light for bactericide treatment has been established
      by tin oxide nanostructures synthesized using a surfactant-assisted solvothermal
      method. Anionic (sodium n-dodecyl sulfate, SDS), cationic (cetyltrimethyl
      ammonium bromide, CTAB) and non-ionic (Tritron X-100) surfactants were used as
      morphology controlling agents. The as-synthesized nanoparticles are characterized
      by X-ray powder diffraction (XRD), UV-vis spectroscopy and scanning electron
      microscopy (SEM). The XRD patterns of the as-synthesized tin oxide nanoparticles
      were well indexed to the tetragonal rutile structure. Nanostructure tin oxide
      powders of about 70-92nm in size have been obtained with different morphologies.
      The spherical, cauliflower, flower petals morphologies of surfactant-mediated
      SnO2 were obtained using X-100, CTAB, and SDS, respectively and the spherical
      like for surfactant-free SnO2 was observed in the SEM micrographs. The surfactant
      mediated SnO2 samples showed absorption edges red shift to longer wavelength and
      increased absorption intensities compared to surfactant-free SnO2. Antibacterial
      effectiveness of SnO2 samples was tested against general Escherichia coli (E.
      coli ATCC 25922) under UV-, visible-light and dark conditions. The surfactant
      promoted antimicrobial effect under visible light by SnO2 band gap modification.
      In contrast, the surfactant-free SnO2 possessed higher photokilling activity
      under UV-light. The antibacterial performance of SnO2 samples as a function of
      their structural and morphological features such as particle size, surface area
      and visible/UV light absorbing capacity was discussed. 

PMID- 24316659
TI  - DNA methylation in oocytes and liver of female mice and their offspring: effects
      of high-fat-diet-induced obesity.
AB  - BACKGROUND: Maternal obesity has adverse effects on oocyte quality, embryo
      development, and the health of the offspring. OBJECTIVES: To understand the
      underlying mechanisms responsible for the negative effects of maternal obesity,
      we investigated the DNA methylation status of several imprinted genes and
      metabolism-related genes. METHODS: Using a high-fat-diet (HFD)-induced mouse
      model of obesity, we analyzed the DNA methylation of several imprinted genes and
      metabolism-related genes in oocytes from control and obese dams and in oocytes
      and liver from their offspring. Analysis was performed using combined bisulfite
      restriction analysis (COBRA) and bisulfite sequencing. RESULTS: DNA methylation
      of imprinted genes in oocytes was not altered in either obese dams or their
      offspring; however, DNA methylation of metabolism-related genes was changed. In
      oocytes of obese mice, the DNA methylation level of the leptin (Lep) promoter was
      significantly increased and that of the Ppar-alpha promoter was reduced.
      Increased methylation of Lep and decreased methylation of Ppar-alpha was also
      observed in the liver of female offspring from dams fed the high-fat diet (OHFD).
      mRNA expression of Lep and Ppar-alpha was also significantly altered in the liver
      of these OHFD. In OHFD oocytes, the DNA methylation level of Ppar-alpha promoter
      was increased. CONCLUSIONS: Our results indicate that DNA methylation patterns of
      several metabolism-related genes are changed not only in oocytes of obese mice
      but also in oocytes and liver of their offspring. These data may contribute to
      the understanding of adverse effects of maternal obesity on reproduction and
      health of the offspring.

PMID- 24316660
TI  - Characterizing focal hepatic lesions by free-breathing intravoxel incoherent
      motion MRI at 3.0 T.
AB  - BACKGROUND: Diffusion-weighted (DW) imaging is commonly used to distinguish
      between benign and malignant liver lesions. PURPOSE: To prospectively evaluate
      the true molecular-diffusion coefficient (D), perfusion-related diffusion
      coefficient (D*), perfusion fraction (f), and ADC of focal hepatic lesions using
      a free-breathing intravoxel incoherent motion (IVIM) DW sequence, and to
      determine if these parameters are useful for characterizing focal hepatic
      lesions. MATERIAL AND METHODS: One hundred and twenty hepatic lesions (34
      metastases, 32 hepatocellular carcinoma [HCC], 33 hemangiomas, and 21 liver
      cysts) in 74 patients were examined. Mean D, D*, f, and ADC values of hepatic
      lesions were compared among pathologies. ROC curve analyses were performed to
      assess the performances of D, D*, f, and ADC values for the characterization of
      liver lesions as benign or malignant. RESULTS: The mean D and ADC values of
      benign lesions were greater than those of malignant lesions (P < 0.001). Although
      the mean D and ADC values of liver cysts were greater than those of hemangiomas
      (P < 0.001), and these values were not significantly different between metastases
      and HCCs (P = 0.99). Area under the ROC curve for ADC values (0.98) was
      significantly greater (P = 0.048) than that for D values (0.96) for the
      differentiation of benign and malignant lesions. Sensitivity and specificity for
      the detection of malignant lesion were 89% and 98%, respectively, when an ADC cut
      off value of 1.40 was applied. CONCLUSION: D and ADC values have more potential
      for characterizing focal hepatic lesions than D* or f values, and for the
      differentiation of malignancy and benignity.

PMID- 24316661
TI  - Transjejunal biliary interventions: going back to a road less traveled.
AB  - Percutaneous transhepatic biliary interventions are not without risk and
      potential complications. In patients with bilioenteric anastomosis in whom repeat
      biliary interventions are expected, percutaneous transjejunal access is a very
      useful approach that is not frequently used nowadays. We provide a brief review
      of the history, indications, and current status of transjejunal biliary
      interventions. Transjejunal biliary access provides a relatively atraumatic
      pathway to the biliary system in patients that need repeat interventions.
      Multiple studies have provided convincing data that in appropriately chosen
      patients receiving a bilioenteric anastomosis, an antecolic limb of jejunum
      should be placed for subsequent access in biliary intervention.

PMID- 24316662
TI  - Radiologic assessment and frequency of idiopathic osteosclerosis of jawbones: an
      interpopulation comparison.
AB  - BACKGROUND: Idiopathic osteosclerosis is a localized growth of compact bone with
      an unknown cause. This asymptomatic lesion is an insignificant finding and as
      such requires no treatment. It should be distinguished from other types of
      osteosclerosis created by inflammatory processes and systemic diseases. PURPOSE:
      To determine the prevalence and distribution of idiopathic osteosclerosis in the
      jawbones in Iran and to compare this prevalence and distribution with other
      populations. MATERIAL AND METHODS: This cross-sectional descriptive study was
      performed in the Dental School of Shahid Beheshti University of Medical Sciences,
      Tehran, between 2010 and 2011. Data were collected from the files of patients who
      underwent panoramic radiography for dental treatment. Location, shape, and
      relation between idiopathic osteosclerosis and the tooth as well as the
      resorption of the tooth involved were evaluated. Lesion distribution regarding
      age, gender, localization, shape, dental relationship, and root resorption was
      assessed using the chi-squared test. RESULTS: In total, 787 panoramic radiographs
      of 456 women and 331 men were assessed. Idiopathic osteosclerosis was detected in
      75 (9.5%) patients. The prevalence of idiopathic osteosclerosis was significantly
      higher in the women (11.8% vs. 6.3%; P < 0.01). The mean age of the patients with
      idiopathic osteosclerosis was 31.9 +/- 17.9 years and 30.8 +/- 13.3 years in the
      patients without idiopathic osteosclerosis. The distribution of idiopathic
      osteosclerosis in the mandible (97.3%), mostly in the premolar region, was
      significantly higher than that in the maxilla (2.7%). CONCLUSION: Our results
      showed high frequencies of idiopathic osteosclerosis in Iran in comparison to
      some other countries.

PMID- 24316663
TI  - Histogram analysis of apparent diffusion coefficient map of diffusion-weighted
      MRI in endometrial cancer: a preliminary correlation study with histological
      grade.
AB  - BACKGROUND: Until now, several investigators have explored the value of diffusion
      weighted magnetic resonance imaging (DWI) for the preoperative tumor grading of
      endometrial cancer. However, the diagnostic value of DWI with quantitative
      analysis of apparent diffusion coefficient (ADC) has been controversial. PURPOSE:
      To explore the role of histogram analysis of ADC maps based on entire tumor
      volume in determining the grade of endometrial cancer. MATERIAL AND METHODS: This
      study was IRB-approved with waiver of informed consent. Thirty-three patients
      with endometrial cancer underwent DWI (b = 0, 600, 1000 s/mm(2)), and
      corresponding ADC maps were acquired. Regions of interest (ROIs) were drawn on
      all slices of the ADC map in which the tumor was visualized including areas of
      necrosis to derive volume-based histographic ADC data. Histogram parameters (5th
      95th percentiles, mean, standard deviation, skewness, kurtosis) were correlated
      with histological grade using one-way ANOVA with Tukey-Kramer test for post hoc
      comparisons, and were compared between high (grade 3) and low (grades 1/2) grade
      using Student t-test. ROC curve analysis was performed to determine the optimum
      threshold value for each parameter, and their corresponding sensitivity and
      specificity. RESULTS: The standard deviation, quartile, 75th, 90th, and 95th
      percentiles of ADC showed significant differences between grades (P <= 0.03 for
      all) and between high and low grades (P <= 0.024 for all). There were no
      significant correlations between tumor grade and other parameters. ROC curve
      analysis yielded sensitivities and specificities of 75% and 96%, 62.5% and 92%,
      100% and 52%, 100% and 72%, and 100% and 88%, using standard deviation, quartile,
      75th, 90th, and 95th percentiles for determining high grade with corresponding
      areas under the curve (AUCs) of 0.787, 0.792, 0.765, 0.880, and 0.925,
      respectively. CONCLUSION: Histogram analysis of ADC maps based on entire tumor
      volume can be useful for predicting the histological grade of endometrial cancer.
      The 90th and 95th percentiles of ADC were the most promising parameters for
      differentiating high from low grade.

PMID- 24316665
TI  - Enhanced thermoelectric performance of Nb-doped SrTiO3 by nano-inclusion with low
      thermal conductivity.
AB  - Authors reported an effective path to increase the electrical conductivity while
      to decrease the thermal conductivity, and thus to enhance the ZT value by nano
      inclusions. By this method, the ZT value of Nb-doped SrTiO3 was enhanced 9-fold
      by yttria stabilized zirconia (YSZ) nano-inclusions. YSZ inclusions, located
      inside grain and in triple junction, can reduce the thermal conductivity by
      effective interface phonon scattering, enhance the electrical conductivity by
      promoting the abnormal grain growth, and thus lead to the obvious enhancement of
      ZT value, which strongly suggests that, it is possible to not only reduce the
      thermal conductivity, but also increase the electrical conductivity by nano
      inclusions with low thermal conductivity. This study will give some useful
      enlightenment to the preparation of high-performance oxide thermoelectric
      materials. 

PMID- 24316664
TI  - Irinotecan disrupts tight junction proteins within the gut : implications for
      chemotherapy-induced gut toxicity.
AB  - Chemotherapy for cancer causes significant gut toxicity, leading to severe
      clinical manifestations and an increased economic burden. Despite much research,
      many of the underlying mechanisms remain poorly understood hindering effective
      treatment options. Recently there has been renewed interest in the role tight
      junctions play in the pathogenesis of chemotherapy-induced gut toxicity. To
      delineate the underlying mechanisms of chemotherapy-induced gut toxicity, this
      study aimed to quantify the molecular changes in key tight junction proteins, ZO
      1, claudin-1, and occludin, using a well-established preclinical model of gut
      toxicity. Female tumor-bearing dark agouti rats received irinotecan or vehicle
      control and were assessed for validated parameters of gut toxicity including
      diarrhea and weight loss. Rats were killed at 6, 24, 48, 72, 96, and 120 h post
      chemotherapy. Tight junction protein and mRNA expression in the small and large
      intestines were assessed using semi-quantitative immunohistochemistry and RT-PCR.
      Significant changes in protein expression of tight junction proteins were seen in
      both the jejunum and colon, correlating with key histological changes and
      clinical features. mRNA levels of claudin-1 were significantly decreased early
      after irinotecan in the small and large intestines. ZO-1 and occludin mRNA levels
      remained stable across the time-course of gut toxicity. Findings strongly suggest
      irinotecan causes tight junction defects which lead to mucosal barrier
      dysfunction and the development of diarrhea. Detailed research is now warranted
      to investigate posttranslational regulation of tight junction proteins to
      delineate the underlying pathophysiology of gut toxicity and identify future
      therapeutic targets. 

PMID- 24316666
TI  - What is the future of acute respiratory distress syndrome after the Berlin
      definition?
AB  - PURPOSE OF REVIEW: To analyze recently published articles in the medical
      literature that studied distinct aspects of adult patients with acute respiratory
      distress syndrome (ARDS) after the new Berlin definition introduced in 2012.
      RECENT FINDINGS: The degree of ARDS severity according to this new classification
      correlated well with extravascular lung water index, pulmonary vascular
      permeability index and the finding of diffuse alveolar damage on autopsy. The new
      possibility of bedside echocardiographic evaluation of biventricular cardiac
      function is indicating the necessity of including a subgroup of severity of
      patients with right ventricular dysfunction. High-resolution CT evaluation showed
      that signs of pulmonary fibroproliferation in early ARDS predict increased
      ventilator dependency, multiple organ failure and mortality. The median
      development of ARDS 1 or 2 days after hospital admission emphasizes the need for
      ARDS intrahospital prevention, especially protective ventilation in non-ARDS
      patients. The better outcome with the use of prone position in patients with
      PaO2/FIO2 below 150 recently observed questioned the Berlin definition thresholds
      to decide the future best treatment strategies according to the proposed degree
      of severity of the syndrome. SUMMARY: The impact of the Berlin definition of ARDS
      on the incidence, better treatment stratification and mortality ratio of ARDS is
      still to be determined.

PMID- 24316667
TI  - Catheter-associated urinary tract infection: a successful prevention effort
      employing a multipronged initiative at an academic medical center.
AB  - An interdisciplinary clinical improvement workgroup was formed at this academic
      medical center with the goal of reducing catheter-associated urinary tract
      infections (CAUTIs). In 2011, the CAUTI rate was noted to be 4.7 CAUTIs per 1000
      catheter days. Rounding by 2 lead clinical nurse specialists revealed
      deficiencies in current practice, which were addressed with multifaceted
      strategies, including evidence-based indwelling urinary catheter and bladder
      management protocols, education of staff, reporting of data, and utilization of
      an icon in the electronic health record (EHR). After the implementation of these
      strategies, the CAUTI rate decreased and was noted to be 2.4 in February 2013. In
      addition to this, there was a downward trend line for catheter days. 

PMID- 24316668
TI  - Discovery of a benzimidazole series of ADAMTS-5 (aggrecanase-2) inhibitors by
      scaffold hopping.
AB  - We describe a medicinal chemistry approach to generate a series of benzimidazoles
      bearing thiazolidin-4-one using scaffold hopping from thiazole 1, our previously
      described thiazole. Our goal was to discover a potent and permeable small
      molecule ADAMTS-5 inhibitor. The results suggest that small compound 22 shows
      promise as a potent small-molecule ADAMTS-5 inhibitor with good permeability. 

PMID- 24316669
TI  - Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide
      derivatives as potent CCR5 inhibitors.
AB  - Based on a putative 'Y shape' pharmacophore model of CCR5 inhibitors, a series of
      novel piperidine-4-carboxamide derivatives were designed and synthesized using a
      group-reverse strategy. Among synthesized target compounds, 16g (IC50 = 25.73 nM)
      and 16i (IC50 = 25.53 nM) showed equivalent inhibitory activity against CCR5 to
      that of the positive control maraviroc (IC50 = 25.43 nM) in calcium mobilization
      assay. Selected compounds were further tested for their antiviral activity in HIV
      1 single cycle assay. Two compounds, 16g and 16i, displayed antiviral activity
      with IC50 values of 73.01 nM and 94.10 nM, respectively. Additionally, the
      pharmacokinetic properties and inhibitory potency against hERG of 16g were
      evaluated, providing a foundation for ongoing optimization.

PMID- 24316670
TI  - Mechanistic studies of photoinduced intramolecular and intermolecular electron
      transfer processes in RuPt-centred photo-hydrogen-evolving molecular devices.
AB  - The photoinduced electron transfer properties of two photo-hydrogen-evolving
      molecular devices (PHEMDs) [(bpy)2Ru(II)(phen-NHCO-bpy-R)Pt(II)Cl2](2+) (i.e.,
      condensation products of [Ru(bpy)2(5-amino-phen)](2+) and (4-carboxy-4'-R
      bpy)PtCl2; bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline; RuPt-COOH for R =
      COOH and RuPt-CN for R = CN) were investigated. RuPt-CN demonstrates higher
      photocatalytic performance relative to RuPt-COOH arising from a larger driving
      force for the intramolecular photoinduced electron transfer (PET) associated with
      a stronger electron-withdrawing effect of R (DeltaGPET = -0.43 eV for RuPt-CN and
      -0.16 eV for RuPt-COOH). This is the first study on PET events using ultrafast
      spectroscopy. Dramatic enhancement is achieved in the rate of PET in RuPt-CN
      (1.78 * 1010 s(-1)) relative to RuPt-COOH (3.1 * 109 s(-1)). For each system, the
      presence of three different conformers giving rise to three different PET rates
      is evidenced, which are also discussed with the DFT results. Formation of a
      charge-separated (CS) state [(bpy)2Ru(III)(phen-NHCO-bpy(-)-R)Pt(II)Cl2](2+) in
      the sub-picosecond time regime and recombination in the picosecond time regime
      are characterized spectrophotometrically. The CS-state formation was found to
      compete with reductive quenching of the triplet excited state by EDTA whose
      dianionic form ion-pairs with dicationic RuPt-COOH. Thus, a key intermediate
      [(bpy)2Ru(II)(phen-NHCO-bpy(-)-R)Pt(II)Cl2](+) (i.e., the one-electron-reduced
      species) prior to the H2 formation was found to be formed either via reduction of
      the CS state by EDTA or via formation of [(bpy)2Ru(II)(phen(-)-NHCO-bpy
      R)Pt(II)Cl2](+) by reductive quenching of the triplet excited state. More
      importantly, it is also shown that some of the conformers in solution possess a
      CS lifetime sufficiently long to drive hydrogen evolution from water.

PMID- 24316671
TI  - Plasma membrane translocation of trimerized MLKL protein is required for TNF
      induced necroptosis.
AB  - The mixed lineage kinase domain-like protein (MLKL) has recently been identified
      as a key RIP3 (receptor interacting protein 3) downstream component of tumour
      necrosis factor (TNF)-induced necroptosis. MLKL is phosphorylated by RIP3 and is
      recruited to the necrosome through its interaction with RIP3. However, it is
      still unknown how MLKL mediates TNF-induced necroptosis. Here, we report that
      MLKL forms a homotrimer through its amino-terminal coiled-coil domain and locates
      to the cell plasma membrane during TNF-induced necroptosis. By generating
      different MLKL mutants, we demonstrated that the plasma membrane localization of
      trimerized MLKL is critical for mediating necroptosis. Importantly, we found that
      the membrane localization of MLKL is essential for Ca(2+) influx, which is an
      early event of TNF-induced necroptosis. Furthermore, we identified that TRPM7
      (transient receptor potential melastatin related 7) is a MLKL downstream target
      for the mediation of Ca(2+) influx and TNF-induced necroptosis. Hence, our study
      reveals a crucial mechanism of MLKL-mediated TNF-induced necroptosis. 

PMID- 24316672
TI  - The bacterial cell division proteins FtsA and FtsZ self-organize into dynamic
      cytoskeletal patterns.
AB  - Bacterial cytokinesis is commonly initiated by the Z-ring, a cytoskeletal
      structure that assembles at the site of division. Its primary component is FtsZ,
      a tubulin superfamily GTPase, which is recruited to the membrane by the actin
      related protein FtsA. Both proteins are required for the formation of the Z-ring,
      but if and how they influence each other's assembly dynamics is not known. Here,
      we reconstituted FtsA-dependent recruitment of FtsZ polymers to supported
      membranes, where both proteins self-organize into complex patterns, such as fast
      moving filament bundles and chirally rotating rings. Using fluorescence
      microscopy and biochemical perturbations, we found that these large-scale
      rearrangements of FtsZ emerge from its polymerization dynamics and a dual,
      antagonistic role of FtsA: recruitment of FtsZ filaments to the membrane and
      negative regulation of FtsZ organization. Our findings provide a model for the
      initial steps of bacterial cell division and illustrate how dynamic polymers can
      self-organize into large-scale structures. 

PMID- 24316673
TI  - Autophagy variation within a cell population determines cell fate through
      selective degradation of Fap-1.
AB  - Autophagy regulates cell death both positively and negatively, but the molecular
      basis for this paradox remains inadequately characterized. We demonstrate here
      that transient cell-to-cell variations in autophagy can promote either cell death
      or survival depending on the stimulus and cell type. By separating cells with
      high and low basal autophagy using flow cytometry, we demonstrate that autophagy
      determines which cells live or die in response to death receptor activation. We
      have determined that selective autophagic degradation of the phosphatase Fap-1
      promotes Fas apoptosis in Type I cells, which do not require mitochondrial
      permeabilization for efficient apoptosis. Conversely, autophagy inhibits
      apoptosis in Type II cells (which require mitochondrial involvement) or on
      treatment with TRAIL in either Type I or II cells. These data illustrate that
      differences in autophagy in a cell population determine cell fate in a stimulus-
      and cell-type-specific manner. This example of selective autophagy of an
      apoptosis regulator may represent a general mechanism for context-specific
      regulation of cell fate by autophagy. 

PMID- 24316675
TI  - Lessons in AIDS vaccine development learned from studies of equine infectious,
      anemia virus infection and immunity.
AB  - Equine infectious anemia (EIA), identified in 1843 [1] as an infectious disease
      of horses and as a viral infection in 1904, remains a concern in veterinary
      medicine today. Equine infectious anemia virus (EIAV) has served as an animal
      model of HIV-1/AIDS research since the original identification of HIV. Similar to
      other lentiviruses, EIAV has a high propensity for genomic sequence and antigenic
      variation, principally in its envelope (Env) proteins. However, EIAV possesses a
      unique and dynamic disease presentation that has facilitated comprehensive
      analyses of the interactions between the evolving virus population, progressive
      host immune responses, and the definition of viral and host correlates of immune
      control and vaccine efficacy. Summarized here are key findings in EIAV that have
      provided important lessons toward understanding long term immune control of
      lentivirus infections and the parameters for development of an enduring broadly
      protective AIDS vaccine. 

PMID- 24316676
TI  - Robust support vector machine-trained fuzzy system.
AB  - Because the SVM (support vector machine) classifies data with the widest
      symmetric margin to decrease the probability of the test error, modern fuzzy
      systems use SVM to tune the parameters of fuzzy if-then rules. But, solving the
      SVM model is time-consuming. To overcome this disadvantage, we propose a rapid
      method to solve the robust SVM model and use it to tune the parameters of fuzzy
      if-then rules. The robust SVM is an extension of SVM for interval-valued data
      classification. We compare our proposed method with SVM, robust SVM, ISVM-FC
      (incremental support vector machine-trained fuzzy classifier), BSVM-FC (batch
      support vector machine-trained fuzzy classifier), SOTFN-SV (a self-organizing TS
      type fuzzy network with support vector learning) and SCLSE (a TS-type fuzzy
      system with subtractive clustering for antecedent parameter tuning and LSE for
      consequent parameter tuning) by using some real datasets. According to
      experimental results, the use of proposed approach leads to very low training and
      testing time with good misclassification rate. 

PMID- 24316677
TI  - LINE1 methylation levels associated with increased bladder cancer risk in pre
      diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study
      participants.
AB  - Global methylation in blood DNA has been associated with bladder cancer risk in
      case-control studies, but has not been examined prospectively. We examined the
      association between LINE1 total percent 5-methylcytosine and bladder cancer risk
      using pre-diagnostic blood DNA from the United States-based, Prostate, Lung,
      Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and
      the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish
      male smokers (391 cases/778 controls). Logistic regression adjusted for age at
      blood draw, study center, pack-years of smoking, and sex was used to estimate odd
      ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific
      methylation quartiles. In PLCO, higher, although non-significant, bladder cancer
      risks were observed for participants in the highest three quartiles (Q2-Q4)
      compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The
      association was stronger in males (Q2-Q4 vs. Q1 OR = 1.48, 95% CI: 1.00-2.20) and
      statistically significant among male smokers (Q2-Q4 vs. Q1 OR = 1.83, 95% CI:
      1.14-2.95). No association was found among females or female smokers. Findings
      for male smokers were validated in ATBC (Q2-Q4 vs. Q1: OR = 2.31, 95% CI: 1.62
      3.30) and a highly significant trend was observed (P = 8.7 * 10(-7)). After
      determining that study data could be combined, pooled analysis of PLCO and ATBC
      male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4
      compared with Q1 (OR = 2.03, 95% CI: 1.52-2.72), and a trend across quartiles was
      observed (P = 0.0001). These findings suggest that higher global methylation
      levels prior to diagnosis may increase bladder cancer risk, particularly among
      male smokers. 

PMID- 24316678
TI  - One-step nucleotide-programmed growth of porous upconversion nanoparticles:
      application to cell labeling and drug delivery.
AB  - A simple and "green" strategy has been reported for the first time to fabricate
      upconversion nanoparticles (UCNPs) by utilizing nucleotides as bio-templates. The
      influence of the functionalities present on the nucleotide on the production of
      nanoparticles was investigated in detail. Through the effects of nucleotides, the
      obtained nanoparticles possessed a porous structure. The use of the as-prepared
      UCNPs for cell imaging, drug delivery and versatile therapy applications were
      demonstrated. In view of the bright up-conversion luminescence as well as the
      excellent biocompatibility, and the good colloidal stability of the as-prepared
      UCNPs, we envision that our synthesis protocol might advance both the fields of
      UCNPs and biomolecule-based nanotechnology for future studies. 

PMID- 24316679
TI  - Randomized trial of a robotic assistive device for the upper extremity during
      early inpatient stroke rehabilitation.
AB  - BACKGROUND: A recent Cochrane Review showed that early robotic training of the
      upper limb in stroke survivors can be more effective than other interventions
      when improving activities of daily living involving the arm function is the aim
      of therapy. OBJECTIVE: We tested for efficacy of the study a protocol which
      involved the use of the NeReBot therapy in partial substitution of standard upper
      limb rehabilitation in post-acute stroke patients. METHODS: In this dose-matched,
      randomized controlled clinical trial, 34 hemiparetic participants with movement
      against gravity in shoulder, elbow, and wrist muscle groups were enrolled within
      15 days of the onset of stroke. All participants received a total daily
      rehabilitation treatment for 120 minutes, 5 days per week for 5 weeks. The
      control group received standard therapy for the upper limb. The experimental
      group received standard therapy (65% of exercise time) associated with robotic
      training (35% of exercise time). Muscle tone (Modified Ashworth Scale), strength
      (Medical Research Council), and synergism (Fugl-Meyer motor scores) were measured
      at impairment level, whereas dexterity (Box and Block Test and Frenchay Arm Test)
      and activities of daily living (Functional Independence Measure) were measured at
      activity level. All assessments were performed at baseline, at the end of therapy
      (time T1), at 3 months (time T2), and at 7 months (time T3) after entry. All
      between-group analyses were tested using nonparametric test with Bonferroni's
      adjustments for multiple testing. RESULTS: No significant between-group
      differences were found with respect to demographic characteristics, motor,
      dexterity, and ADLs at baseline, postintervention (T1) and at follow-up (T2 and
      T3). CONCLUSIONS: The robot therapy by NeReBot did not lead to better outcomes
      compared with conventional inpatient rehabilitation.

PMID- 24316680
TI  - Anogenital distance and penile length in infants with hypospadias or
      cryptorchidism: comparison with normative data.
AB  - BACKGROUND: Anogenital distance (AGD) in animals is a sensitive biomarker of
      fetal endocrine disruption and the associated testicular dysgenesis syndrome
      (TDS). However, AGD in human infants with cryptorchidism and hypospadias, which
      are potential manifestations of TDS during childhood, is not clearly described.
      OBJECTIVE: Our aim was to compare AGD in boys with cryptorchidism or hypospadias
      against normative data. METHODS: Boys with isolated cryptorchidism (n = 71, age
      13.4 +/- 5.8 months) or hypospadias (n = 81, age 11.4 +/- 6.2 months) were
      recruited from a tertiary center for measurement of AGD and penile length; they
      were compared with 487 healthy full-term boys from a birth cohort by deriving age
      specific standard deviation scores (SDS). RESULTS: Boys with cryptorchidism were
      older (p = 0.048) compared with boys with hypospadias. Boys with hypospadias had
      shorter mean AGD and penile length SDS than healthy boys (both p < 0.0001). Mean
      AGD and penile length SDS values in boys with cryptorchidism were longer than
      mean values in boys with hypospadias (both p < 0.01) and shorter than mean values
      in healthy boys (both p < 0.0001). Mean penile length SDS decreased as the
      severity of hypospadias increased (ptrend = 0.078). CONCLUSIONS: In the study
      population, AGD and penile length were reduced in boys with hypospadias or
      cryptorchidism relative to normative data derived from a longitudinal birth
      cohort. The findings support the use of AGD as a quantitative biomarker to
      examine the prenatal effects of exposure to endocrine disruptors on the
      development of the male reproductive tract.

PMID- 24316681
TI  - Discordance in HIV-positive patient and health care provider perspectives on
      death, dying, and end-of-life care.
AB  - The purpose of this study was to investigate how HIV-positive patients and
      infectious disease health care providers think about death, dying, and end-of
      life care (EOLC) planning. We conducted separate in-depth qualitative interviews
      with 47 patients and 11 providers. Interview data were transcribed and analyzed
      using a secondary comparative method. Patients and providers demonstrated
      profound differences in their perspectives on patient empowerment and
      attributions of control related to disease progression, imminence of death, and
      EOLC decision making. Notably, patients described fears related to life-extending
      interventions that generally went unaddressed within the clinical context. We
      argue for the routinization of EOLC discussions and suggest novel research
      approaches to improve patient empowerment and medical engagement. 

PMID- 24316682
TI  - Polymorphism and magnetic properties of Li2MSiO4 (M = Fe, Mn) cathode materials.
AB  - Transition metal-based lithium orthosilicates (Li2MSiO4, M = Fe, Ni, Co, Mn) are
      gaining a wide interest as cathode materials for lithium-ion batteries. These
      materials present a very complex polymorphism that could affect their physical
      properties. In this work, we synthesized the Li2FeSiO4 and Li2MnSiO4 compounds by
      a sol-gel method at different temperatures. The samples were investigated by
      XRPD, TEM, (7)Li MAS NMR, and magnetization measurements, in order to
      characterize the relationships between crystal structure and magnetic properties.
      High-quality (7)Li MAS NMR spectra were used to determine the silicate structure,
      which can otherwise be hard to study due to possible mixtures of different
      polymorphs. The magnetization study revealed that the Neel temperature does not
      depend on the polymorph structure for both iron and manganese lithium
      orthosilicates. 

PMID- 24316683
TI  - Revision and destabilization of acrylic-pin external skeletal fixation
      constructions using a conventional soldering iron.

PMID- 24316684
TI  - Radioxenon detections in the CTBT international monitoring system likely related
      to the announced nuclear test in North Korea on February 12, 2013.
AB  - Observations made in April 2013 of the radioxenon isotopes (133)Xe and (131m)Xe
      at measurement stations in Japan and Russia, belonging to the International
      Monitoring System for verification of the Comprehensive Nuclear-Test-Ban Treaty,
      are unique with respect to the measurement history of these stations. Comparison
      of measured data with calculated isotopic ratios as well as analysis using
      atmospheric transport modeling indicate that it is likely that the xenon measured
      was created in the underground nuclear test conducted by North Korea on February
      12, 2013, and released 7-8 weeks later. More than one release is required to
      explain all observations. The (131m)Xe source terms for each release were
      calculated to 0.7 TBq, corresponding to about 1-10% of the total xenon inventory
      for a 10 kt explosion, depending on fractionation and release scenario. The
      observed ratios could not be used to obtain any information regarding the fissile
      material that was used in the test. 

PMID- 24316685
TI  - Post-Chernobyl 137Cs in the atmosphere of Thessaloniki: a consequence of the
      financial crisis in Greece.
AB  - The background radiation level of (137)Cs at the urban atmosphere of Thessaloniki
      has been increased during the recent decade only due to the Fukushima accident
      fallout. Since then, no other signal of (137)Cs was observed until the winter
      period of 2013, when slightly elevated (137)Cs concentrations were measured. The
      (137)Cs signals observed were up to 12 MUBq m(-3), mainly during holidays and
      weekends followed by lower or even non-detectable activities in the next working
      days. Those episodes are attributed to the increase of biomass products
      combustion for residential heating as this year the tax of oil for heating was
      drastically raised as a consequence of the financial crisis. A preliminary survey
      of various wood products as well as of bottom ashes from different domestic
      burning devices is presented. (137)Cs concentrations up to 11 Bq kg(-1) were
      measured in wood products and up to 500 Bq kg(-1) in ash samples. 

PMID- 24316686
TI  - Field study of using naturally occurring radon to assess the dense non-aqueous
      phase liquid distribution in saturated zone.
AB  - The concept of radon deficiency such as the ratios of radon concentrations to the
      maximum measured value of a sample batch was employed as the survey methodology
      for this study to investigate contamination sources in an industrial zone that
      was suspected of causing subsurface dense non-aqueous phase liquid (DNAPL)
      contamination. The results showed that radon concentrations in certain wells were
      significantly lower than that in uncontaminated regions. Radon concentrations in
      groundwater are influenced by the in situ bioremediation of vegetable oil, which
      causes abnormal reductions of the radon in groundwater because radon partitions
      into vegetable oil and results in more variable for the radon deficit method to
      showing the impacts of remediation. Six contaminated regions were identified by
      integrating radon concentration ratios (divided into low (L), middle (M), and
      high (H) levels) and DNAPL concentrations (divided into low (L) and high (H)
      levels). Contaminated regions in the LH, MH, and HH categories are located in the
      vicinity of the contamination source, and those in the HL category are located
      far from the source zone. The ML and LL categories indicate the involvement of
      unknown factors, and that additional analyses are required to uncover the facts
      that affect radon and DNAPL concentrations. 

PMID- 24316687
TI  - Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa:
      controversies and clinical implications.
AB  - PURPOSE OF REVIEW: To examine the role of two nutritional factors implicated in
      the healthy aging of the Okinawans: caloric restriction; and traditional foods
      with potential caloric restriction-mimetic properties. RECENT FINDINGS: Caloric
      restriction is a research priority for the US National Institute on Aging.
      However, little is known regarding health effects in humans. Some caloric
      restriction-related outcomes, such as cause-specific mortality and lifespan, are
      not practical for human clinical trials. Therefore, epidemiological data on older
      Okinawans, who experienced a caloric restriction-like diet for close to half
      their lives, are of special interest. The nutritional data support mild caloric
      restriction (10-15%) and high consumption of foods that may mimic the biological
      effects of caloric restriction, including sweet potatoes, marine-based carotenoid
      rich foods, and turmeric. Phenotypic evidence is consistent with caloric
      restriction (including short stature, low body weight, and lean BMI), less age
      related chronic disease (including cardiovascular diseases, cancer, and
      dementia), and longer lifespan (mean and maximum). SUMMARY: Both caloric
      restriction and traditional Okinawan functional foods with caloric restriction
      mimetic properties likely had roles in the extended healthspan and lifespan of
      the Okinawans. More research is needed on health consequences of caloric
      restriction and foods with caloric restriction-mimetic properties to identify
      possible nutritional interventions for healthy aging.

PMID- 24316691
TI  - What happens in Vegas...

PMID- 24316688
TI  - Dietary protein is beneficial to bone health under conditions of adequate calcium
      intake: an update on clinical research.
AB  - PURPOSE OF REVIEW: To underscore recent clinical studies, which evaluate the
      association between dietary protein and bone health. RECENT FINDINGS:
      Epidemiologic studies show greater protein intake to be beneficial to bone health
      in adults. In addition, randomized controlled trials show that protein's positive
      effect on bone health is augmented by increased calcium intake. The relation
      between dietary protein and fracture risk is unclear. Dietary protein may
      positively impact bone health by increasing muscle mass, increasing calcium
      absorption, suppressing parathyroid hormone, and augmenting insulin-like growth
      factor 1 production; but the effects of other factors that contribute to this
      association, such as dietary protein dose and timing response, require further
      research. SUMMARY: The positive effects of protein intake on bone health may only
      be beneficial under conditions of adequate calcium intake. Dietary protein's
      relation with fracture risk requires further investigation.

PMID- 24316693
TI  - Key advances in the chemical modification of nanocelluloses.
AB  - Nanocelluloses, including nanocrystalline cellulose, nanofibrillated cellulose
      and bacterial cellulose nanofibers, have become fascinating building blocks for
      the design of new biomaterials. Derived from the must abundant and renewable
      biopolymer, they are drawing a tremendous level of attention, which certainly
      will continue to grow in the future driven by the sustainability trend. This
      growing interest is related to their unsurpassed quintessential physical and
      chemical properties. Yet, owing to their hydrophilic nature, their utilization is
      restricted to applications involving hydrophilic or polar media, which limits
      their exploitation. With the presence of a large number of chemical
      functionalities within their structure, these building blocks provide a unique
      platform for significant surface modification through various chemistries. These
      chemical modifications are prerequisite, sometimes unavoidable, to adapt the
      interfacial properties of nanocellulose substrates or adjust their hydrophilic
      hydrophobic balance. Therefore, various chemistries have been developed aiming to
      surface-modify these nano-sized substrates in order to confer to them specific
      properties, extending therefore their use to highly sophisticated applications.
      This review collocates current knowledge in the research and development of
      nanocelluloses and emphasizes more particularly on the chemical modification
      routes developed so far for their functionalization. 

PMID- 24316694
TI  - Microglia specific fluorescent probes for live cell imaging.
AB  - Small molecule fluorescent probes offer significant advantages over conventional
      antibody and fluorescent protein labeling techniques. Here we present and , dyes
      that label live microglia specifically. They may be applied to the isolation and
      imaging of live microglia when investigating their role in neuroinflammatory
      diseases. 

PMID- 24316695
TI  - ANO1 as a marker of oral squamous cell carcinoma and silencing ANO1 suppresses
      migration of human SCC-25 cells.
AB  - OBJECTIVES: The purpose of this study is to confirm that ANO1 correlates with
      occurrence and metastasis of OSCC. STUDY DESIGN: Immunohistochemistry was used to
      detect the expression of ANO1 in 160 specimens of OSCC and normal tissues.
      Lentiviral silencing ANO1 was used in SCC-25 cell line to study the cell
      migration and cell detachment. RESULTS: Immunohistochemical staining revealed
      that ANO1 was expressed in a large majority (132 out of 160, 82.5%) of OSCC
      specimens and that the rate of ANO1 expression in OSCC was significantly higher
      than that of normal tissue (P<0.05); The rate of ANO1 expression was higher in
      metastatic tumors than in non-metastatic tumors, and the difference was
      significant (P<0.05). The results of cell migration assay showed that the
      percentage of cells through the membrane was 26.61 +/-0.81 in assay group, and
      54.26 +/-3.74 in control group, respectively (t=-16.22,P<0.0001). The results of
      cell detachment assay showed that the percentage of cells detachment was 37.42 +/
      0.90 in assay group, and 87.38 +/-1.59 in control group, respectively (t=-62.34,
      P<0.0001). The results of wound healing assay showed the assay group had a
      reduced migration rate compared with the control group in 32 h (F=1038.78,
      P<0.0001). Wound closure was no significantly different between the assay and
      control cells when DIDS was used in wound healing assay (F=4.61,P>0.05).
      CONCLUSIONS: Our study shows that abnormal expression of ANO1 correlated with the
      occurrence and metastasis of OSCC in clinical specimens and that silencing ANO1
      greatly reduced migration ability of scc-25 cells. Calcium activated chloride
      channel activity of ANO1 promoted the cell migration. Thus, ANO1 could represent
      a new diagnostic biomarker and a potentially important therapeutic target of
      OSCC.

PMID- 24316696
TI  - Etiology, distribution, treatment modalities and complications of maxillofacial
      fractures.
AB  - PURPOSE: This study evaluated the trends and factors associated with
      maxillofacial fractures treated from 1997 to 2007 in the Oral and Maxillofacial
      Surgery Department of the Clermont-Ferrand University Hospital. METHODS: This
      study included 364 patients of which 82% were men and 45%, 20-29-years old. The
      etiology, anatomical distribution, treatment modality and complications of
      maxillofacial fractures were examined. RESULTS: Overall, interpersonal violence,
      traffic accidents and falls were the most common mechanisms of injury. There was
      a decreasing trend in traffic accidents and increasing one in falls as a cause of
      fracture over the 11-years period of this study. Young male patients were
      preferentially victim of interpersonal violence and traffic accidents, while
      middle-aged ones were of falls and work-related accidents. Middle-aged female
      patients were preferentially victim of traffic accidents and interpersonal
      violence, while older ones were of falls. And the number of fractures per patient
      varied according to the mechanism of injury: low after work-related accidents and
      high after traffic accidents. About two-third of fractures involved the mandible.
      Most of these mandibular fractures were treated by osteosynthesis with or without
      intermaxillary fixation, with the proportion of the latter increasing over time.
      There were very few postoperative infections and only in mandible. CONCLUSIONS:
      Maxillofacial fractures predominantly occur in young men, due to interpersonal
      violence. There is nevertheless an increasing trend in falls as a cause of
      fracture, especially in female patients, consistent with the increasing trend in
      presentation of older people. Most maxillofacial fractures involve the mandible
      and there is an increasing trend in treating these fractures by osteosynthesis
      without intermaxillary fixation. Antibiotic prophylaxis associated with dental
      hygiene care can be indicated to prevent postoperative infections.

PMID- 24316697
TI  - Prospective double-blind clinical trial evaluating the effectiveness of Bromelain
      in the third molar extraction postoperative period.
AB  - OBJECTIVES: To evaluate the anti-inflammatory and analgesic effect of Bromelain
      (pineapple extract) administered orally in the postoperative after extraction of
      impacted lower molars. STUDY DESIGN: This is a prospective, placebo-controlled,
      unicentric, double-blind study; the sample size was 34 patients. The pre and
      postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included
      inflamtion, pain and oral aperture, as well as the need for analgesics. One group
      received Bromelain 150mg per day for three days and 100mg on days 4 to 7. The
      other group received placebo in the same dosage. All outcomes werrecorded
      quantitatively and analyzed with the Mann-Whitney U test for independent samples.
      RESULTS: Although there were no statistically significant differences between the
      treatment groups, a trend towards less inflammation and improved oral aperture
      was observed in the group that received Bromelain, compared to the group that
      received placebo. This trend can be attributed completely to random reasons,
      since there is no statistical difference in the results. CONCLUSIONS: Further
      studies are necessary to analyze different administration patterns and doses of
      Bromelain for the use in the postoperative of impacted third molars.

PMID- 24316698
TI  - Exclusion of PAX9 and MSX1 mutation in six families affected by tooth agenesis. A
      genetic study and literature review.
AB  - OBJECTIVE: In the present study, it is describe the phenotypical analysis and the
      mutational screening, for genes PAX9 and MSX1, of six families affected by severe
      forms of tooth agenesis associated with other dental anomalies and systemic
      entities. STUDY DESIGN: Six families affected by severe tooth agenesis associated
      with other dental anomalies and systemic entities were included. Oral
      exploration, radiological examination, medical antecedents consideration and
      mutational screening for PAX9 and MSX1 were carried out. RESULTS: No mutations
      were discovered despite the fact that numerous teeth were missing. An important
      phenotypical variability was observed within the probands, not being possible to
      establish a parallelism with the patterns associated to previously described PAX9
      and MSX1 mutations. CONCLUSIONS; These results bring us to conclude that probably
      other genes can determine phenotypical patterns of dental agenesis in the
      families studied, different than the ones described in the mutations of PAX9 and
      MSX1. Moreover, epigenetic factors can be involved, as those that can reduce gene
      dosage and other post-transcriptional modulation agents, causing dental agenesis
      associated or not with systemic anomalies.

PMID- 24316700
TI  - Serotypes of Aggregatibacter actinomycetemcomitans in relation to periodontal
      status and geographic origin of individuals-a review of the literature.
AB  - OBJECTIVE: Several studies have focused on the relationship among serotype
      distribution, ethnical status and geographic populations, and periodontal
      conditions. Studies that have investigated the prevalence and the distribution of
      A. actinomycetemcomitans serotypes and the relation between the different
      serotypes of the bacterium and periodontal status were reviewed. MATERIAL AND
      METHODS: A systematic literature search for publications regarding the
      distribution of A. actinomycetemcomitans serotypes in subgingival samples of
      periodontitis patients and periodontally healthy subjects by employing polymerase
      chain reaction (PCR) was conducted. RESULTS: From the 85 studies identified in
      the first analysis, only 12 met all inclusion and exclusion criteria. Clinical
      isolates from diverse geographic populations with different periodontal
      conditions were evaluated. Serotypes a, b and c were largely found, and serotype
      c was the most prevalent. They were isolated from various periodontal conditions,
      including aggressive periodontitis. CONCLUSIONS: The available literature
      suggests that serotypes a, b, and c are globally dominant, serotypes d and e are
      rare, and the prevalence of the most recently identified serotype f is still
      unknown. It is widely accepted that distribution patterns of A.
      actinomycetemcomitans vary among subjects of different ethnicity and geographic
      regions. The correlation of different serotypes with various periodontal
      conditions remains unclear.

PMID- 24316699
TI  - Anesthetic efficacy of Oraqix(r) versus Hurricaine(r) and placebo for pain
      control during non-surgical periodontal treatment.
AB  - OBJECTIVES: To evaluate the efficacy of Oraqix(r) during scaling and root planing
      (SRP) in comparison with 20% benzocaine and placebo. STUDY DESIGN: 15 patients
      requiring 4 sessions of SRP were enrolled. For each patient, Oraqix(r),
      Hurricaine(r), vaseline or no anesthetic product were randomly assigned each to a
      quadrant. Treatment pain was evaluated on a 100 mm Visual Analog Scale (VAS) and
      on a Verbal Rating Scale (VRS). The amount of product administered, the need to
      re-anesthetise, patient and operator satisfaction and the onset of side-effects
      were also recorded. RESULTS: Oraqix(r) was significantly better than nothing,
      with a reduction of VAS score to 13.3 units, but without significant differences
      with Vaseline or Hurricaine(r). Oraqix(r) was better in VRS reduction than not
      using any anesthetic (p=0.001) or using vaseline (p=0.024), but similar to
      Hurricaine(r) (p=0.232). CONCLUSIONS: Oraqix(r) effectively controls pain in SRP
      procedures, with few side-effects and a good acceptance on the part of patients
      and clinicians.

PMID- 24316701
TI  - Narrow-diameter implants: are they a predictable treatment option? A literature
      review.
AB  - OBJECTIVE: To evaluate the predictability of narrow-diameter implants as a
      treatment option in routine clinical practice. A literature review was performed
      of studies reporting clinical results obtained with these implants. Survival
      rates, peri-implant bone loss and related complications were evaluated. The
      working hypothesis was that narrow-diameter implants offer clinical results
      similar to those obtained with implants of greater diameter. MATERIAL AND
      METHODS: A Medline-PubMed search covering the period between 2002 and 2012 was
      carried out. Studies published in English and with a follow-up period of at least
      12 months were considered for inclusion. A manual search was also conducted in
      different journals with an important impact factor. results: Twenty-one studies
      meeting the screening criteria were included in the literature review. A total of
      2980 narrow-diameter implants placed in 1607 patients were analyzed. CONCLUSIONS:
      The results obtained from the literature indicate that narrow-diameter implants
      are a predictable treatment option, since they afford clinical results comparable
      to those obtained with implants of greater diameter.

PMID- 24316702
TI  - Demographic profile of oral nonodontogenic cysts in a Brazilian population.
AB  - OBJECTIVES: The purpose of this study was to determine the clinical and
      demographic characteristics of oral non-odontogenic cysts (ONOC) in a Brazilian
      population over a 53-year period and to compare this data with the literature.
      STUDY DESIGN: A total of 20.391 biopsies records were evaluated, from April/1959
      to August/2012. Cases of oral developmental cysts were selected. Data regarding
      age, gender, time of evolution, and anatomic site of all cases were collected.
      The data were analyzed by descriptive statistics. RESULTS: Among 20.391 oral
      biopsies, 71 (0.35%) met the criteria of ONOC. Females accounted for 50.70% of
      all cases. The mean age observed was 38.14 years (range: 5-88 years).
      Nasopalatine duct cysts, oral lymphoepithelial cysts and epidermoid cysts were
      the most common ONOC, accounting for 63 cases (88.73%). Nasopalatine duct cysts
      occurred in 31 cases (43.66%), followed by 22 patients with oral lymphoepithelial
      cysts (30.99%) and 10 cases of epidermoid cysts (14.08%). Nasopalatine duct cysts
      revealed predominance among males (58.06). Oral lymphoepithelial cysts were more
      commonly observed in tongue (50%). Epidermoid cysts were most frequently found in
      the buccal mucosa (40.00%). CONCLUSIONS: The differential diagnosis of ONOC is
      based on the clinical, radiological, and histological findings. It is difficult
      to establish an epidemiological profile of ONOCs, considering the low frequency
      of these lesions and the divergences in the demographic and clinical presentation
      data among different populations.

PMID- 24316703
TI  - Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of
      oral squamous cell carcinoma.
AB  - The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell
      carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early
      carcinogenesis have been found in mucosa near carcinomas, which is considered a
      model to study field cancerization. The aim of the present study is to analyze
      NOS2 expression at the histologically normal margins of OSCC. STUDY DESIGN:
      Eleven biopsy specimens of OSCC containing histologically normal margins (HNM)
      were analyzed. Ten biopsies of normal oral mucosa were used as controls. The
      activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and
      nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi
      squared test was applied. RESULTS: Six out of the eleven HNM from carcinoma
      samples showed positive NOS2 activity whereas all the control group samples
      yielded negative (p=0.005). No statistically significant association between
      enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and
      nitrite was found. CONCLUSION: NOS2 expression would be an additional evidence of
      alterations that may occur in a state of field cancerization before the
      appearance of potentially malignant morphological changes.

PMID- 24316704
TI  - Plasma variations in stress markers: clinical trial of two anesthetics used in
      regional block in the extraction of impacted inferior third molars.
AB  - OBJECTIVES: Was to evaluate the effect of different regional anesthetics
      (articaine with epinephrine versus prilocaine with felypressin) on stress in the
      extraction of impacted lower third molars in healthy subjects. STUDY DESIGN:
      [corrected] A prospective single-blind, split-mouth cross-over randomized study
      was designed, with a control group. The experimental group consisted of 24
      otherwise healthy male volunteers, with two impacted lower third molars which
      were surgically extracted after inferior alveolar nerve block (regional
      anesthesia), with a fortnight's interval: the right using 4% articaine with
      1:100.000 epinephrine, and the left 3% prilocaine with 1:1.850.000 felypressin.
      Patients were randomized for the first surgical procedure. To analyze the
      variation in four stress markers, homovanillic acid, 3-methoxy-4
      hydroxyphenylglycol, prolactin and cortisol, 10-mL blood samples were obtained at
      t = 0, 5, 60, and 120 minutes. The control group consisted of 12 healthy
      volunteers, who did not undergo either extractions or anesthetic procedures but
      from whom blood samples were collected and analyzed in the same way. RESULTS:
      Plasma cortisol increased in the experimental group (multiple range test,
      P<0.05), the levels being significantly higher in the group receiving 3%
      prilocaine with 1:1.850,000 felypressin (signed rank test, p<0.0007). There was a
      significant reduction in homovanillic acid over time in both groups (multiple
      range test, P<0.05). No significant differences were observed in homovanillic
      acid, 3-methoxy-4-hydroxyphenylglycol or prolactin concentrations between the
      experimental and control groups. CONCLUSIONS: The effect of regional anesthesia
      on stress is lower when 4% articaine with 1:100,000 epinephrine is used in this
      surgical procedure.

PMID- 24316705
TI  - The clinical characteristics of benign oral mucosal tumors.
AB  - OBJECTIVES: To investigate the clinical characteristics and pre- biopsy
      provisional diagnoses of benign oral mucosal tumors. MATERIAL AND METHODS: A 10-
      year retrospective analysis of all benign tumors of the oral mucosa, from a
      university- affiliated oral and maxillofacial surgery department. RESULTS: 146
      benign tumors were included. The mean age was 49.6 years, with an approximately
      equal gender distribution. The most prevalent tumor types were lipomatous tumors
      (27.4%), vascular (23.3%), and salivary gland tumors (16.5%). Tongue, labial and
      buccal mucosa were the most frequently involved sites. The vast majority (98.6%)
      presented as non-ulcerated masses. Only 2 (1.4%) presented as ulcerated masses.
      The clinical provisional diagnosis correctly classified lesions as non-malignant
      in 93.3%. In only 9 (6.7%) suspicion of malignancy was included in the
      provisional diagnosis. However, benignneoplasia was unsuspected in 42.1% of
      tumors. These cases were clinically classified as reactive. CONCLUSION: Benign
      tumors were most likely to be clinically correctly classified as non-malignant,
      but even in the setting of experienced oral surgeons, neoplasia was unsuspected
      in more than 40% of cases. This data strongly supports the need to biopsy every
      oral mucosal mass, since inaccurate clinical evaluation of the lesion's
      biological nature was a frequent event.

PMID- 24316706
TI  - Risk factors for temporomandibular disorder: binary logistic regression analysis.
AB  - OBJECTIVE: To analyze the influence of socioeconomic and demographic factors
      (gender, economic class, age and marital status) on the occurrence of
      temporomandibular disorder. STUDY DESIGN: One hundred individuals from urban
      areas in the city of Recife (Brazil) registered at Family Health Units was
      examined using Axis I of the Research Diagnostic Criteria for Temporomandibular
      Disorders (RDC/TMD) which addresses myofascial pain and joint problems (disc
      displacement, arthralgia, osteoarthritis and oesteoarthrosis). The Brazilian
      Economic Classification Criteria (CCEB) was used for the collection of
      socioeconomic and demographic data. Then, it was categorized as Class A (high
      social class), Classes B/C (middle class) and Classes D/E (very poor social
      class). The results were analyzed using Pearson's chi-square test for
      proportions, Fisher's exact test, nonparametric Mann-Whitney test and Binary
      logistic regression analysis. RESULTS: None of the participants belonged to Class
      A, 72% belonged to Classes B/C and 28% belonged to Classes D/E. The multivariate
      analysis revealed that participants from Classes D/E had a 4.35-fold greater
      chance of exhibiting myofascial pain and 11.3-fold greater chance of exhibiting
      joint problems. CONCLUSION: Poverty is a important condition to exhibit
      myofascial pain and joint problems.

PMID- 24316707
TI  - Efficacy of platelet-rich plasma applied to post-extraction retained lower third
      molar alveoli. A systematic review.
AB  - Dental retentions have a high prevalence among the general population and their
      removal can involve multiple complications. The use of platelet rich plasma has
      been proposed in an attempt to avoid these complications, as it contains high
      growth factors and stimulates diverse biological functions that facilitate the
      healing of soft and hard tissues. OBJECTIVES: To evaluate the available
      scientific evidence related to the application of platelet-rich plasma in the
      post-extraction alveoli of a retained lower third molars. MATERIAL AND METHODS: A
      systematic review of published literature registered in the Medline, EMBASE,
      Cochrane and NIH databases. The following categories were included: human
      randomized clinical studies. Key search words were: platelet rich plasma;
      platelet rich plasma and oral surgery; platelet rich in growth factors and third
      molar. RESULTS: Of 101 potentially valid articles, seven were selected, of which
      four were rejected as they failed to meet quality criteria. Three studies
      fulfilled all selection and quality criteria: Ogundipe et al.; Rutkowski et al.;
      Haraji et al. The studies all measured osteoblast activity by means of
      sintigraphy, and also registered pain, bleeding, inflammation, temperature,
      numbness as perceived by the patients, radiological bone density and the
      incidence of alveolar osteitis. CONCLUSIONS: Scientific evidence for the use of
      PRP in retained third molar surgery is poor. For this reason randomized clinical
      trials are needed before recommendations for the clinical application of PRP can
      be made.

PMID- 24316708
TI  - Influence of occlusal loading on peri-implant clinical parameters. A pilot study.
AB  - OBJECTIVES: To investigate the relation between occlusal loading and peri-implant
      clinical parameters (probing depth, bleeding on probing, gingival retraction,
      width of keratinized mucosa, and crevicular fluid volume) in patients with
      implant-supported complete fixed prostheses in both arches. MATERIAL AND METHODS:
      This clinical study took place at the University of Valencia (Spain) dental
      clinic. It included patients attending the clinic for regular check-ups during at
      least 12 months after rehabilitation of both arches with implant-supported
      complete fixed ceramo-metallic prostheses. One study implant and one control
      implant were established for each patient using the T-Scan(r)III computerized
      system (Tesco, South Boston, USA). The maxillary implant closest to the point of
      maximum occlusal loading was taken as the study implant and the farthest (with
      least loading) as the control. Occlusal forces were registered with the T-Scan(r)
      III and then occlusal adjustment was performed to distribute occlusal forces
      correctly. Peri-implant clinical parameters were analyzed in both implants before
      and two and twelve months after occlusal adjustment. RESULTS: Before occlusal
      adjustment, study group implants presented a higher mean volume of crevicular
      fluid (51.3 +/- 7.4 UP) than the control group (25.8 +/- 5.5 UP), with
      statistically significant difference. Two months after occlusal adjustment, there
      were no significant differences between groups (24.6 +/- 3.8 UP and 26 +/- 4.5 UP
      respectively) (p=0.977). After twelve months, no significant differences were
      found between groups (24.4 +/- 11.1 UP and 22.5 +/- 8.9 UP respectively)
      (p=0.323). For the other clinical parameters, no significant differences were
      identified between study and control implants at any of the study times (p>0.05).
      CONCLUSIONS: Study group implants receiving higher occlusal loading presented
      significantly higher volumes of crevicular fluid than control implants.
      Crevicular fluid volumes were similar in both groups two and twelve months after
      occlusal adjustment.

PMID- 24316709
TI  - The effects of informed consent format on preoperative anxiety in patients
      undergoing inferior third molar surgery.
AB  - OBJECTIVE: To evaluate the effect of informed consent format on preoperative
      anxiety of patients. MATERIAL AND METHODS: We performed a prospective study (91
      patients) undergoing lower third molar extraction. Patients were distributed into
      three groups. Informed consent for surgery was obtained through a written
      document, an oral interview or a video recording. Afterwards, patients were asked
      about their anxiety level and the effect the informed consent had had on it.
      RESULTS: Whereas the information conveyed both in oral and written formats
      relieved the patient to some extent (in a scale of -3 to +3) 0.97 +/- 1.21 and
      0.29 +/- 0.97, respectively), the video recording increased patient's anxiety in
      a statistically significant way (in a scale of -3 to +3, -0.57 +/- 1.43). The
      difference obtained between the values obtained in oral and written information
      was not statistically significant. DISCUSSION: The most adequate format,
      according to our study, would be the oral format.

PMID- 24316710
TI  - Clinical and laboratorial profile and histological features on minor salivary
      glands from patients under investigation for Sjogren's syndrome.
AB  - Diagnosis of Sjogren's syndrome (SS) is complex and the usefulness of labial
      minor salivary glands biopsy in this process remains controversial. OBJECTIVE: to
      evaluate the clinical and laboratorial profile and histological features on
      labial minor salivary glands from patients under investigation of SS. STUDY
      DESIGN: clinical charts from 38 patients under suspicion of SS and submitted to
      labial minor salivary glands biopsies were reviewed. Clinical and laboratorial
      data were retrieved from the clinical files and the HE-stained histological
      slides were reviewed under light microscopy. RESULTS: mean age of the patients
      was 56.5 years and 97% were females; histological analysis showed that 42% of the
      cases showed ductal dilatation, lymphocytic foci were found in 52.6% and, from
      this group, 80% of the cases presented a foci/lobules ratio above 0.8.
      Acinar/ductal ratio was considered diminished in 39.5% of the samples. Thirty six
      (95%) and 32 (84%) patients, respectively, complained about xerostomia and
      xerophthalmia. A study of the time interval of the symptoms that led to SS
      investigation showed a mean of 116 months. Moreover, sixty-six percent of the
      patients had already been submitted to immunosuppressive therapy prior to the
      labial minor salivary gland biopsy. Age of the patients, scintigraphic
      alterations on salivary function, antinuclear factor (ANF), anti-Ro and anti-La
      did not show statistical significant association with the histological features.
      Lobules/foci ratio above 0.8 was the only histological parameter statistically
      associated with Sjogren's syndrome diagnosis (p<0.0001). CONCLUSIONS: in the
      studied sample, lymphocytic foci on salivary glands were the only histological
      parameter associated to the diagnosis of SS. Early indication of labial minor
      salivary gland biopsy to patients under investigation of SS could limit the
      effects of immunosuppressive therapy on the histological features associated with
      the evolution of salivary gland involvement in SS.

PMID- 24316711
TI  - Comparison of the effect of naproxen, etodolac and diclofenac on postoperative
      sequels following third molar surgery: a randomised, double-blind, crossover
      study.
AB  - OBJECTIVE: To compare the three non-steroidal anti-inflammatory agents (NSAIDs)
      Diclofenac potassium, Etodolac and Naproxen sodium in relation to pain, swelling
      and trismus following impacted third molar surgery. STUDY DESIGN: The study was a
      randomized and a double-blinded study which included 42 healthy young individuals
      with impacted third molars and bone retention. Patients were randomly assigned to
      3 groups (n: 14) to which Diclofenac potassium, Naproxen sodium and Etodolac were
      administered orally an hour before the operation. Impacted third molars were
      surgically extracted with local anaesthesia. Visual analog scales (VAS) were used
      to assess the pain in the 6th, 12th hours and on the 1st, 2nd, 3rd, 5th, and 7th
      days postoperatively. Swelling was evaluated using ultrasound (US) and mouth
      opening (trismus) was measured with a composing stick pre and post operatively on
      the 2nd and 7th days respectively. RESULTS: Regarding pain alleviation,
      Diclofenac potassium was better than Naproxen sodium and Naproxen sodium was
      better than Etodolac but these differences were not statistically significant. US
      measurements showed that the swelling on postoperative 2nd day was significantly
      lowest with Diclofenac potassium as compared to others (p= 0.027) while Naproxen
      sodium and Etodolac acted similarly (p=0.747). No difference was noted regarding
      trismus in any of the groups. CONCLUSION: NSAIDs (Diclofenac, Naproxen and
      Etodolac) are somehow similarly effective for controlling pain and trismus
      following extraction of mandibular third molars but Diclofenac potassium
      surpasses others in reduction of swelling.

PMID- 24316712
TI  - Single-blind randomized clinical trial to evaluate clinical and radiological
      outcomes after one year of immediate versus delayed implant placement supporting
      full-arch prostheses.
AB  - PURPOSE: To evaluate and compare peri-implant health, marginal bone loss and
      success of immediate and delayed implant placement for rehabilitation with full
      arch fixed prostheses. MATERIAL AND METHODS: The present study was a prospective,
      randomized, single-blind, clinical preliminary trial. Patients were randomized
      into two treatment groups. In Group A implants were placed immediately post
      extraction and in Group B six months after extraction. The following control time
      points were established: one week, six months and twelve months after loading.
      Measurements were taken of peri-implant crevicular fluid volume, plaque index,
      gingival retraction, keratinized mucosa, probing depth, modified gingival index
      and presence of mucositis. Implant success rates were evaluated for the two
      groups. The study sample included fifteen patients (nine women and six men) with
      a mean average age of 63.7 years. One hundred and forty-four implants were
      placed: 76 placed in healed sites and 68 placed immediately. RESULTS: At the
      moment of prosthetic loading, keratinized mucosa width and probing depth were
      higher in immediate implants than delayed implants, with statistically
      significant differences. However, after six and twelve months, differences
      between groups had disappeared. Bone loss was 0.54 +/- 0.39 mm for immediate
      implants and 0.66 +/- 0.25 mm for delayed implants (p=0.201). No implants failed
      in either group. CONCLUSIONS: The present study with a short follow-up and a
      small sample yielded no statistically significant differences in implant success
      and peri-implant marginal bone loss between immediate and delayed implants with
      fixed full-arch prostheses. Peri-implant health showed no statistically
      significant differences for any of the studied parameters (crevicular fluid
      volume, plaque index, gingival retraction, keratinized mucosa, probing depth,
      modified gingival index and presence of mucositis) at the twelve-month follow-up.

PMID- 24316713
TI  - Proposal for a new staging system for osteoradionecrosis of the mandible.
AB  - A new staging system for osteoradionecrosis of the mandible has been
      retrospectively applied to a group of 31 patients. In this system
      clinicoradiographic signs and symptoms are incorporated in a simplified manner.
      For imaging purposes the use of plain radiographs such as periapical films and
      panoramic radiographs is recommended, mainly because of their readily
      availability. The presented staging system seems well reproducible, facilitating
      the comparison of study groups dealing with the various issues of
      osteoradionecrosis of the mandible. It is yet to be evaluated whether the
      presently proposed staging system is useful for management purposes. 

PMID- 24316714
TI  - HS-1793, a resveratrol analogue, induces cell cycle arrest and apoptotic cell
      death in human breast cancer cells.
AB  - Resveratrol, a polyphenolic compound, is a naturally occurring phytochemical and
      is found in a variety of plants, including food such as grapes, berries and
      peanuts. It has gained much attention for its potential anticancer activity
      against various types of human cancer. However, the usefulness of resveratrol as
      a chemotherapeutic agent is limited by its photosensitivity and metabolic
      instability. In this study the effects of a synthetic analogue of resveratrol, HS
      1793, on the proliferation and apoptotic cell death were investigated using MCF-7
      (wild-type p53) and MDA-MB-231 (mutant p53) human breast cancer cells. HS-1793
      inhibited cell growth and induced apoptotic cell death in a concentration
      dependent manner. The induction of apoptosis was determined by morphological
      changes, cleavage of poly(ADP-ribose) poly-merase, alteration of Bax/Bcl-2
      expression ratio and caspase activities. Flow cytometric analysis revealed that
      HS-1793 induced G2/M arrest in the cell cycle progression in both types of cells.
      Of note, HS-1793 induced p53/p21WAF1/CIP1-dependent apoptosis in MCF-7 cells,
      whereas it exhibited p53-independent apoptosis in MDA-MB-231 cells. Furthermore,
      HS-1793 showed more potent anticancer effects in several aspects compared to
      resveratrol in MCF-7 and MDA-MB-231 cells. Thus, these findings suggest that HS
      1793 has potential as a candidate chemotherapeutic agent against human breast
      cancer.

PMID- 24316715
TI  - A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation.
AB  - N(6)-methyladenosine (m(6)A) is the most prevalent and reversible internal
      modification in mammalian messenger and noncoding RNAs. We report here that human
      methyltransferase-like 14 (METTL14) catalyzes m(6)A RNA methylation. Together
      with METTL3, the only previously known m(6)A methyltransferase, these two
      proteins form a stable heterodimer core complex of METTL3-METTL14 that functions
      in cellular m(6)A deposition on mammalian nuclear RNAs. WTAP, a mammalian
      splicing factor, can interact with this complex and affect this methylation. 

PMID- 24316716
TI  - A fluorescence-Raman dual-imaging platform based on complexes of conjugated
      polymers and carbon nanotubes.
AB  - The present study describes a flexible nanoplatform based on electrostatic
      assembly of conjugated polyelectrolytes (CPEs) and carboxylated multi-walled
      carbon nanotubes (cMWNTs). It is demonstrated that the obtained nanocomposites
      inherit intrinsic optical properties of CPEs and characteristic Raman vibration
      modes of MWNTs, providing a fluorescence-Raman dual-imaging method for
      intracellular tracking and locating of MWNTs. We suggest that the cellular
      internalization of the CPE-cMWNT nanocomposites is a surface charge-dependent
      process. The strengths of this nanoplatform include satisfying biocompatibility,
      enhanced protein-repellent property, and ease of implementation, making it
      available for both in vitro and in vivo applications. 

PMID- 24316717
TI  - Cells susceptible to epithelial-mesenchymal transition are enriched in stem-like
      side population cells from prostate cancer.
AB  - Accumulating evidence suggests that epithelial-mesenchymal transition (EMT) acts
      as an important factor for the promotion of tumor progression. Strategies for
      suppressing EMT remain the subject of ongoing research. In the present study,
      fluorescence-activated cell sorting (FACS) was used to isolate side population
      (SP) cells from human prostate cancer (PCa) cell lines and xenograft tissues.
      After identifying their molecular and functional stem-like characteristics, stem
      like SP cells from a cell line and from xenograft tissue were transfected with
      hypoxia inducible factor-1alpha (HIF-1alpha). The potential of the prostate stem
      like SP cells to undergo EMT was compared with that in their bulk counterparts
      after HIF-1alpha introduction. Stem-like SP cells acquired more complete EMT
      molecular features and exhibited stronger aggressive capability than the
      homologous bulk population cells both in vitro (proliferation and invasion) and
      in vivo (tumorigenesis and metastasis formation). We, therefore, concluded that
      EMT is closely associated with tumor heterogeneity, and that PCa cells
      susceptible to EMT are enriched in stem-like SP cells. These findings disclose a
      new approach, targeting the cellular basis of the EMT process that may help to
      identify effective and accurate methods for suppressing tumor growth and
      preventing distant dissemination.

PMID- 24316718
TI  - A variational method in out-of-equilibrium physical systems.
AB  - We propose a new variational principle for out-of-equilibrium dynamic systems
      that are fundamentally based on the method of Lagrange multipliers applied to the
      total entropy of an ensemble of particles. However, we use the fundamental
      equation of thermodynamics on differential forms, considering U and S as 0-forms.
      We obtain a set of two first order differential equations that reveal the same
      formal symplectic structure shared by classical mechanics, fluid mechanics and
      thermodynamics. From this approach, a topological torsion current emerges of the
      form , where Aj and omegak denote the components of the vector potential
      (gravitational and/or electromagnetic) and where omega denotes the angular
      velocity of the accelerated frame. We derive a special form of the Umov-Poynting
      theorem for rotating gravito-electromagnetic systems. The variational method is
      then applied to clarify the working mechanism of particular devices. 

PMID- 24316721
TI  - Death related to Ibuprofen, valdecoxib, and medical errors: case report and
      medicolegal issues.

PMID- 24316720
TI  - Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERalpha
      alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A,
      MBD2, and HDAC2) in the mouse seminal vesicle.
AB  - BACKGROUND: Diethylstilbestrol (DES) is a synthetic estrogen associated with
      adverse effects on reproductive organs. DES-induced toxicity of the mouse seminal
      vesicle (SV) is mediated by estrogen receptor alpha (ERalpha), which alters
      expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin (Ltf)
      genes. OBJECTIVES: We examined a role for nuclear receptor activity in
      association with DNA methylation and altered gene expression. METHODS: We used
      the neonatal DES exposure mouse model to examine DNA methylation patterns via
      bisulfite conversion sequencing in SVs of wild-type (WT) and ERalpha-knockout
      (alphaERKO) mice. RESULTS: The DNA methylation status at four specific CpGs (
      160, -237, -306, and -367) in the Svs4 gene promoter changed during mouse
      development from methylated to unmethylated, and DES prevented this change at 10
      weeks of age in WT SV. At two specific CpGs (-449 and -459) of the Ltf gene
      promoter, DES altered the methylation status from methylated to unmethylated.
      Alterations in DNA methylation of Svs4 and Ltf were not observed in alphaERKO
      SVs, suggesting that changes of methylation status at these CpGs are ERalpha
      dependent. The methylation status was associated with the level of gene
      expression. In addition, gene expression of three epigenetic modifiers-DNMT3A,
      MBD2, and HDAC2-increased in the SV of DES-exposed WT mice. CONCLUSION: DES
      induced hormonal toxicity resulted from altered gene expression of Svs4 and Ltf
      associated with changes in DNA methylation that were mediated by ERalpha.
      Alterations in gene expression of DNMT3A, MBD2, and HDAC2 in DES-exposed male
      mice may be involved in mediating the changes in methylation status in the SV.
      CITATION: Li Y, Hamilton KJ, Lai AY, Burns KA, Li L, Wade PA, Korach KS. 2014.
      Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERalpha
      alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A,
      MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect 122:262
      268; http://dx.doi.org/10.1289/ehp.1307351.

PMID- 24316722
TI  - Authors' reply: NSAIDs and small kidneys in a workers' compensation death claim.

PMID- 24316723
TI  - Urinary nitrate, thiocyanate, and perchlorate and serum thyroid endpoints based
      on NHANES 2001 to 2002 by Bruce et al.

PMID- 24316724
TI  - Do zero-cost workers' compensation medical claims really have zero costs? The
      impact of workplace injury on group health insurance utilization and costs.
AB  - OBJECTIVE: Previous research suggests that non-workers' compensation (WC)
      insurance systems, such as group health insurance (GHI), Medicare, or Medicaid,
      at least partially cover work-related injury and illness costs. This study
      further examined GHI utilization and costs. METHODS: Using two-part model, we
      compared those outcomes immediately after injuries for which accepted WC medical
      claims made zero or positive medical payments. RESULTS: Controlling for pre
      injury GHI utilization and costs and other covariates, our results indicated that
      post-injury GHI utilization and costs increased regardless of whether a WC
      medical claim was zero or positive. The increases were highest for zero-cost WC
      medical claims. CONCLUSION: Our national estimates showed that zero-cost WC
      medical claims alone could cost the GHI $212 million per year.

PMID- 24316727
TI  - Discharge huddle outfitted with mobile technology improves efficiency of
      transitioning stroke patients into follow-up care.
AB  - Disjointed patient care is a well-documented problem in health care systems,
      often stemming from poor communication between providers, services, and follow-up
      care resources. A multidisciplinary discharge huddle, augmented with cellular and
      tablet technology, was implemented on the Neurology Stroke Service to facilitate
      multidisciplinary communication, improve transition of patients, and increase
      referrals into affiliated follow-up care. After initiating the huddle, patient
      length of stay decreased by 1.4 days (25%), patient flow into continuum partners
      increased by 10%, and the number of patients going without services after their
      hospital stay decreased by more than 12%. Huddle members reported that the
      technology was helpful, heavily utilized, and made their work more efficient.
      This pilot suggests that utilizing modern mobile technologies can help improve
      efficiency and referrals within the health care system and reduce patient length
      of stay. 

PMID- 24316728
TI  - Series of edge-sharing bi-triangle Ln4 clusters with a MU4-NO3- bridge:
      syntheses, structures, luminescence, and the SMM behavior of the Dy4 analogue.
AB  - A series of Ln4 clusters, [Ln4L2(MU3-OH)2(MU4-NO3)(NO3)4(OCH3)(H2O)].xMeCN.yMeOH
      (Ln = Gd (1), Tb (2), Dy (3), Ho (4), Er (5), Yb (6), L = 2-{[2-(2-hydroxy
      ethoxy)-ethylimino]-methyl}-6-methoxyphenol), have been synthesized by the
      reaction of Ln(NO)3 and a Schiff-base ligand formed in situ. The six complexes
      display similar structures, with an overall metal core comprising two edge
      sharing triangular Ln3 units linked by a MU4-NO3(-) bridge. The luminescence
      spectrum of complex 2 shows the characteristic emission of the Tb(III) ions. The
      magnetic susceptibility studies reveal that the Ln(III) ions are very weakly
      interacting in all six compounds. Frequency dependence of the ac-susceptibility
      was found for 3, suggesting a typical single-molecule magnet (SMM) behavior with
      an anisotropic barrier of 28 K. 

PMID- 24316729
TI  - Migraine and dizziness.
AB  - PURPOSE OF REVIEW: Awareness of the importance of migraine in patients with
      symptoms of vestibular dysfunction is increasing. This article gives an overview
      of the multiple facets of the link between migraine and vestibular dysfunction.
      RECENT FINDINGS: The vestibular and the headache community have published a
      consensual definition of vestibular migraine, which is an important step to
      promote research on the topic and the awareness of clinicians. Vestibular
      migraine is considered the most common cause of spontaneous recurrent vertigo. So
      far, the evidence for vestibular migraine has been mainly epidemiological, but
      the recent follow-up of a cohort over 9 years could show the robustness of the
      diagnosis over time.Additionally, migraine and vestibular dysfunction have
      multiple potential interactions and links through a range of comorbidities such
      as Meniere's disease, benign paroxysmal positional vertigo, anxiety and motion
      sickness, which go beyond the diagnostic entity of vestibular migraine. SUMMARY:
      The further refinement and wider acceptance of the diagnostic entity of
      vestibular migraine is an important development as it is one the most common
      vestibular disorders. But the relationship between migraine and vestibular
      dysfunction is complex and has many aspects beyond vestibular migraine.

PMID- 24316731
TI  - Highly flexible, transparent and self-cleanable superhydrophobic films prepared
      by a facile and scalable nanopyramid formation technique.
AB  - A facile and scalable technique to fabricate optically transparent, mechanically
      flexible and self-cleanable superhydrophobic films for practical solar cell
      applications is proposed. The superhydrophobic films were fabricated simply by
      transferring a transparent porous alumina layer, which was prepared using an
      anodic aluminium oxidation (AAO) technique, onto a polyethylene terephthalate
      (PET) film with a UV-curable polymer adhesive layer, followed by the subsequent
      formation of alumina nano pyramids (NPs) through the time-controlled chemical
      etching of the transferred porous alumina membrane (PAM). It was found
      experimentally that the proposed functional films can ensure the
      superhydrophobicity in the Cassie-Baxter wetting mode with superior water
      repellent properties through a series of experimental observations including
      static contact angle (SCA), contact angle hysteresis (CAH), sliding behaviour on
      the tilted film, and dynamic behaviour of the liquid droplet impacting on the
      film. In addition to the superior surface wetting properties, an optical
      transmittance of ~79% at a light wavelength of 550 nm was achieved. Furthermore,
      there was no significant degradation in both the surface wetting properties and
      morphology even after 1500-cycles of repetitive bending tests, which indicates
      that the proposed superhydrophobic film is mechanically robust. Finally, the
      practicability of the proposed self-cleanable film was proven quantitatively by
      observing the changes in the power conversion efficiency (PCE) of a photovoltaic
      device covering the film before and after the cleaning process. 

PMID- 24316730
TI  - PRDX1 and PRDX6 are repressed in papillary thyroid carcinomas via BRAF V600E
      dependent and -independent mechanisms.
AB  - Many clinical studies highlight the dichotomous role of PRDXs in human cancers,
      where they can exhibit strong tumor-suppressive or tumor-promoting functions.
      Recent evidence suggests that lower expression of PRDXs correlates with cancer
      progression in colorectal cancer (CRC) or in esophageal squamous carcinoma. In
      the thyroid, increased levels of PRDX1 has been described in follicular adenomas
      and carcinomas, as well as in thyroiditis, while reduced levels of PRDX6 has been
      found in follicular adenomas. We studied the expression of PRDX1 and PRDX6, in a
      series of thyroid tissue samples, covering different thyroid diseases, including
      13 papillary thyroid carcinomas (PTCs). Our results show that PRDX1 and PRDX6 are
      significantly reduced in all PTCs compared to normal tissues, to non-neoplastic
      tissue (MNG) or follicular neoplasms. This reduction is strongly evident in PTCs
      harboring BRAF V600E (31% of our cases). Using TPC-1 and BCPAP and FRTL-5 cell
      lines, we demonstrate for the first time that the presence of BRAF V600E is
      responsible of the hypoexpression of PRDX1 and PRDX6 both at mRNA and protein
      levels. Finally, independently of BRAF status, we observe an interesting
      correlation between the tumor size, the presence of lymph node metastasis and the
      lowest PRDX1 and PRDX6 levels. Therefore, these data indicate that PRDX1 and
      PRDX6 expression not only may play a key role in papillary thyroid carcinogenesis
      via a BRAF V600E-dependent mechanism, but their determination could be considered
      as potential tumor marker for indicating tumor progression in PTCs, independently
      of BRAF status.

PMID- 24316732
TI  - A family of oxide-carbide-carbon and oxide-nitride-carbon nanocomposites.
AB  - This paper describes a powerful and versatile approach that combines the benefits
      of sol-gel processing with controlled phase separation to yield oxide-carbide
      carbon or oxide-nitride-carbon nanocomposites. 

PMID- 24316733
TI  - Organ donation in Muslim countries: the case of Malaysia.
AB  - BACKGROUND: The aim of this paper is to look into the factors influencing
      Malaysian Muslims' decision to become deceased organ donors in Malaysia. MATERIAL
      AND METHODS: We approached 900 Malaysian Muslims and 779 participated in our
      survey, conducted in Kuala Lumpur and its suburb. We examined their willingness
      to become donors and the willing donors were asked why they did not pledge to
      become donors. Non-donors were asked why they refuse to become donors. RESULTS:
      The survey found the main reason for Malaysian Muslims not pledging their organs
      was due to their lack of information on organ donation and/or their lack of
      confidence in the government's ability to properly administer organ donation
      procedures. Another interesting finding is that religion is not a main deterrent
      to organ donation. CONCLUSIONS: The survey suggests that Malaysia can explore
      many ways to encourage organ donation without having to resort to the highly
      controversial financial incentive option. A key to Malaysia's success or failure
      to increase organ donation rate lies in its ability to persuade its Muslim
      population (its largest population) to donate organs. This can be done by
      adopting a segmented, focused, and highly localized form of public education and
      by leveraging on existing networks involving local religious and community
      leaders as well as government and non-governmental institutions.

PMID- 24316734
TI  - Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC.
AB  - Non-small cell lung cancer (NSCLC) is one of the most common malignant tumours in
      the western world and is associated with a poor prognosis. Biomarkers predicting
      prognosis and therapeutic effects are highly required, and cell-free DNA (cfDNA)
      may be a feasible option. Genetic mutations can be analysed in plasma and may
      increase the scientific use of such measurements. In the present study, we
      investigated: i) the dynamics of cfDNA and plasma mutated KRAS (pmKRAS) during
      the treatment of patients with advanced NSCLC; and ii) the prognostic value of
      baseline cfDNA and pmKRAS. Sixty-nine patients were included in a prospective
      biomarker trial. Inclusion criteria included advanced NSCLC, candidate for first
      line treatment, no previous cancer within the five years prior to this study.
      Blood samples were drawn at baseline, day 8 and at progression. Analyses of cfDNA
      and KRAS mutations in plasma were performed using an in-house qPCR assay.
      Evaluation of the treatment effect and status at follow-up was performed
      according to RECIST 1.1. The median levels of cfDNA were significantly higher at
      progression (9,250 alleles/ml) than at baseline (5,450 alleles/ml). Overall
      survival and progression-free survival were both significantly shorter in
      patients with high levels of cfDNA (above the 75th percentile) compared to lower
      levels. Only few patients harboured KRAS mutations in plasma. Two patients had no
      KRAS mutations in plasma at baseline, but mutations appeared in the subsequent
      blood samples. High baseline levels of cfDNA indicate a poor prognosis. The level
      changes during the treatment course with a significant increase at progression,
      suggesting a possible predictive value of cfDNA. The plasma KRAS status may
      change during treatment with potential implications for treatment selection.

PMID- 24316735
TI  - Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial
      signaling pathway.
AB  - Autophagy is linked to cell death, yet the associated mechanisms are largely
      undercharacterized. We discovered that melanoma, which is generally resistant to
      drug-induced apoptosis, can undergo autophagic cell death with the participation
      of orphan nuclear receptor TR3. A sequence of molecular events leading to
      cellular demise is launched by a specific chemical compound, 1-(3,4,5
      trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3
      targeting compounds. The autophagic cascade comprises TR3 translocation to
      mitochondria through interaction with the mitochondrial outer membrane protein
      Nix, crossing into the mitochondrial inner membrane through Tom40 and Tom70
      channel proteins, dissipation of mitochondrial membrane potential by the
      permeability transition pore complex ANT1-VDAC1 and induction of autophagy. This
      process leads to excessive mitochondria clearance and irreversible cell death. It
      implicates a new approach to melanoma therapy through activation of a
      mitochondrial signaling pathway that integrates a nuclear receptor with autophagy
      for cell death. 

PMID- 24316736
TI  - E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin.
AB  - Weak protein interactions between ubiquitin and the ubiquitin-proteasome system
      (UPS) enzymes that mediate its covalent attachment to substrates serve to
      position ubiquitin for optimal catalytic transfer. We show that a small-molecule
      inhibitor of the E2 ubiquitin-conjugating enzyme Cdc34A, called CC0651, acts by
      trapping a weak interaction between ubiquitin and the E2 donor ubiquitin-binding
      site. A structure of the ternary CC0651-Cdc34A-ubiquitin complex reveals that the
      inhibitor engages a composite binding pocket formed from Cdc34A and ubiquitin.
      CC0651 also suppresses the spontaneous hydrolysis rate of the Cdc34A-ubiquitin
      thioester without decreasing the interaction between Cdc34A and the RING domain
      subunit of the E3 enzyme. Stabilization of the numerous other weak interactions
      between ubiquitin and UPS enzymes by small molecules may be a feasible strategy
      to selectively inhibit different UPS activities. 

PMID- 24316737
TI  - Genomic mining of prokaryotic repressors for orthogonal logic gates.
AB  - Genetic circuits perform computational operations based on interactions between
      freely diffusing molecules within a cell. When transcription factors are combined
      to build a circuit, unintended interactions can disrupt its function. Here, we
      apply 'part mining' to build a library of 73 TetR-family repressors gleaned from
      prokaryotic genomes. The operators of a subset were determined using an in vitro
      method, and this information was used to build synthetic promoters. The promoters
      and repressors were screened for cross-reactions. Of these, 16 were identified
      that both strongly repress their cognate promoter (5- to 207-fold) and exhibit
      minimal interactions with other promoters. Each repressor-promoter pair was
      converted to a NOT gate and characterized. Used as a set of 16 NOT/NOR gates,
      there are >10(54) circuits that could be built by changing the pattern of input
      and output promoters. This represents a large set of compatible gates that can be
      used to construct user-defined circuits. 

PMID- 24316740
TI  - Experimental model of cutaneous radiation injury in rabbits.
AB  - PURPOSE: To describe an experimental model of cutaneous radiation injury in
      rabbits. METHODS: On this study eight six-month-old New Zealand male rabbits,
      with an average weight of 2.5 kg were used. They were distributed in four groups
      (n=2 per group). The control group did not receive radiotherapy and the others
      received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively.
      Photographic analysis and histopathological evaluation of the irradiated areas
      were carried out. RESULTS: After 30 days, the animals from the control group had
      all their hair grown. In spite of that, the animals from group 2000 cGy had a 60
      day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the
      3000 cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4.
      One of the animals from group 4500 cGy died on the 7th day with visceral
      necrosis. The other from the same group had total skin necrosis. A progressive
      reduction of glands and blood vessels count and an increase on collagen
      deposition was observed. CONCLUSION: The proposed experimental model is
      reproductable. This study suggests that the dosage 4500 cGy is excessive and the
      3000 cGy is the most effective for this experimental model of cutaneous radiation
      injury in rabbits.

PMID- 24316739
TI  - Protonation drives the conformational switch in the multidrug transporter LmrP.
AB  - Multidrug antiporters of the major facilitator superfamily couple proton
      translocation to the extrusion of cytotoxic molecules. The conformational changes
      that underlie the transport cycle and the structural basis of coupling of these
      transporters have not been elucidated. Here we used extensive double electron
      electron resonance measurements to uncover the conformational equilibrium of
      LmrP, a multidrug transporter from Lactococcus lactis, and to investigate how
      protons and ligands shift this equilibrium to enable transport. We find that the
      transporter switches between outward-open and outward-closed conformations,
      depending on the protonation states of specific acidic residues forming a
      transmembrane protonation relay. Our data can be framed in a model of transport
      wherein substrate binding initiates the transport cycle by opening the
      extracellular side. Subsequent protonation of membrane-embedded acidic residues
      induces substrate release to the extracellular side and triggers a cascade of
      conformational changes that concludes in proton release to the intracellular
      side. 

PMID- 24316738
TI  - VMAT2 identified as a regulator of late-stage beta-cell differentiation.
AB  - Cell replacement therapy for diabetes mellitus requires cost-effective generation
      of high-quality, insulin-producing, pancreatic beta cells from pluripotent stem
      cells. Development of this technique has been hampered by a lack of knowledge of
      the molecular mechanisms underlying beta-cell differentiation. The present study
      identified reserpine and tetrabenazine (TBZ), both vesicular monoamine
      transporter 2 (VMAT2) inhibitors, as promoters of late-stage differentiation of
      Pdx1-positive pancreatic progenitor cells into Neurog3 (referred to henceforth as
      Ngn3)-positive endocrine precursors. VMAT2-controlled monoamines, such as
      dopamine, histamine and serotonin, negatively regulated beta-cell
      differentiation. Reserpine or TBZ acted additively with dibutyryl adenosine 3',5'
      cyclic AMP, a cell-permeable cAMP analog, to potentiate differentiation of
      embryonic stem (ES) cells into beta cells that exhibited glucose-stimulated
      insulin secretion. When ES cell-derived beta cells were transplanted into AKITA
      diabetic mice, the cells reversed hyperglycemia. Our protocol provides a basis
      for the understanding of beta-cell differentiation and its application to a cost
      effective production of functional beta cells for cell therapy. 

PMID- 24316741
TI  - Rapid prototyping of three-dimensional biomodels as an adjuvant in the surgical
      planning for intracranial aneurysms.
AB  - PURPOSE: To fabricate a three-dimensional biomodels of intracranial aneurysms,
      using rapid prototyping technology, to facilitate optimal anatomical
      visualization of aneurysms prior to and during surgery. METHODS: Four
      intracranial aneurysms cases were selected for this study. Using CT angiography
      images, the rapid prototyping process was completed using a PolyJet technology
      machine. The size and morphology of the prototypes were compared to brain digital
      subtraction arteriography of the same patients. RESULTS: The biomodels reproduced
      the exact location and morphology of the intracranial aneurysms, particularly the
      necks, in life-size dimensions and exactly the same as measured by digital
      subtraction arteriography. The arterial segments adjacent to the aneurysm and
      arteries anatomically known by the surgeon were also shown, which could guide the
      surgeon to the aneurysmal segment. The models showed an average unit cost of US$
      130 and each one took an average of 20 hours to be fabricated. CONCLUSIONS: It is
      possible to fabricate 3D physical biomodels of intracranial aneurysms from CT
      angiography images. These prototypes may be useful in the surgical planning for
      intracranial aneurysms to clarify the anatomy, define surgical techniques and
      facilitate the choice of suitable materials, such as clips and clip appliers.

PMID- 24316742
TI  - Transumbilical endoscopic cholecystectomy in a porcine model.
AB  - PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a new
      technique. This study describes our initial experience of NOTES and investigates
      the feasibility of transumbilical endoscopic cholecystectomy (TUEC). METHODS:
      Eight domestic pigs were submitted to TUEC. After establishment of
      pneumoperitoneum, a bi-channel endoscope was placed through an infra-umbilical
      trocar. The gallbladder fundus was lifted by a grasper. The cystic duct and
      artery was dissected with a flexible hook and clipped by a clip fixing device.
      The specimen was extracted through the infra-umbilical trocar. RESULTS: The mean
      operation time was 114 minutes, ranging from 75 to 155 minutes. All the
      gallbladders were removed successfully. There was one case of subtotal resection,
      two cases of bleeding and three cases of bile leakage. CONCLUSION: Transumbilical
      endoscopic cholecystectomy is feasible although it needs more support of
      experiments and techniques before being applied on human subjects.

PMID- 24316743
TI  - Ischemia and reperfusion of rat small intestine using pentoxyfilline and
      prostaglandin E1.
AB  - PURPOSE: To investigate the small intestinal tissue alterations in rats submitted
      to ischemia and tissue reperfusion using pentoxyfilline or prostaglandin E1.
      METHODS: Thirty five Wistar rats were used, distributed into group control (A)
      n=10 were submitted to intestinal ischemia and reperfusion during 60 minutes and
      no one drug have been utilized. In the group pentoxyfilline (B) n=10 have been
      utilized during tissue ischemia and reperfusion as well as prostaglandin E1 (C)
      n=10, but separately. In the group sham (D) n=5, the animals were submitted to
      surgical. After euthanasia of the animals, a segment of the small intestine was
      cut, stained by hematoxilin-eosin and histological analysis according to Chiu
      criteria. RESULTS: Histological results showed that using pentoxyflline or
      prostaglandin E1 the results during tissue reperfusion were better, since the
      levels of criteria from Chiu that predominated were level 2 and 3, indicating
      less tissue damage in comparison to the control group (group A) that showed
      levels 4 and 5, what means more severe histological tissue alterations.
      CONCLUSION: Use of pentoxyfilline or prostaglandin E1 promoted a beneficial
      effect during intestinal reperfusion, demonstrated by less severe histological
      lesions in the small intestine mucosa of rats submitted to ischemia and tissue
      reperfusion when helped by the drugs.

PMID- 24316744
TI  - Evidence of presynaptic and postsynaptic action of local anesthetics in rats.
AB  - PURPOSE: To assess the probable actions of ropivacaine, 50% enantiomeric excess
      bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission
      in vitro. METHODS: Thirty rats were distributed into groups (n=5) according to
      the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The
      concentration used for the three local anesthetics (LA) was 5 ug.mL. (-1)The
      following parameters were evaluated: 1) LA effects on membrane potential (MP) and
      miniature end plate potential (MEPP). A chick biventer cervicis preparation was
      also used to evaluate LA effects on the contracture response to acetylcholine.
      RESULTS: LA did not alter MP values and decreased the frequency and amplitude of
      MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and
      levobupivacaine decreased the contracture response to acetylcholine with
      statistical significance, in comparison to ropivacaine. CONCLUSIONS: In the
      concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited
      presynaptic and postsynaptic actions evidenced by alterations in miniature end
      plate potentials and contracture response to acetylcholine. Ropivacaine only had
      a presynaptic action.

PMID- 24316745
TI  - Laparoscopic nephrectomy with single-portal access Gelpoint(r)in swines.
AB  - PURPOSE: To analyze the viability of using Gelpoint(r) (single-port access) to
      make partial and total nephrectomy in pigs and to describe the technical
      difficulties found during these surgical procedures. METHODS: Ten pigs (Landrace
      specie) with 20 kg in average were distributed in two groups. Group A: total
      right nephrectomy and Group B: partial left nephrectomy. The procedures were
      performed inside the Surgical Technique Room from Pontificia Universidade
      Catolica do Parana (PUCPR). RESULTS: In Group A, time to single-port insertion
      varied from one to two minutes and total time of the procedures were 20.4 +/- 8.2
      minutes. Bleeding was under than 20 mL in 70% of animals. Time of instrument
      excision was 20.7 +/- 12 seconds and time of hilum dissection was 3.9 +/- 2.2
      minutes. In Group B, after total contralateral nephrectomy two surgical
      procedures were not concluded due to bleeding. In this group, time of surgery was
      6.8 +/- 4.2 minutes. With the exception of the second surgery, the highest blood
      volume loss was 50 mL. The mean excision time was 22.3 +/- 22.3 seconds.
      CONCLUSION: Total and partial nephrectomy through umbilical single-access using
      GelPoint(r) was feasible and safe in pigs.

PMID- 24316746
TI  - Influence of the peritoneal lavage with bupivacaine on the survival and
      resistance of colonic anastomoses performed under fecal peritonitis in rats.
AB  - PURPOSE: To evaluate the effects of peritoneal lavage with bupivacaine on
      survival and initial resistance of anastomosis on distal colon, performed under
      peritonitis or not. METHODS: Forty rats, weighing from 300 to 350 g (321.29 +/-
      11.3 1g), were randomly divided in four groups and underwent laparotomy and
      anastomosis on the distal colon six hours after induction of peritonitis by
      intraperitoneal injection of autologous fecal material or not. Group 1: No
      peritonitis and lavage with 3 ml NS; Group 2: No peritonitis and lavage with 8
      mg.kg-1 (+/- 0.5 mL) of 0.5% bupivacaine added to 2.5 mL of NS; Group 3:
      Peritonitis and lavage with 3 ml NS; Group 4: Peritonitis and lavage with 8 mg.kg
      1 (+/- 0.5 mL) of 0.5% bupivacaine added to 2.5 mL of NS. Necropsies were
      performed on the animals that died and the time of death was recorded. Surviving
      animals were submitted to euthanasia on the fifth post-operative day and Total
      Energy of Rupture biomechanical test (TER) was applied. RESULTS: Group 4 showed
      survival increase compared to Group 3, without statistical significance. Group 3
      presented the smallest average TER, with statistical significance. CONCLUSION:
      Peritonitis increased mortality and influenced negatively the resistance of colic
      anastomosis in rats. Peritoneal lavage with bupivacaine increased anastomotic
      resistance.

PMID- 24316747
TI  - The spectrum of non alcoholic fatty liver disease in morbidly obese patients:
      prevalence and associate risk factors.
AB  - PURPOSE: To determine the prevalence of non alcoholic fatty liver disease (NAFLD)
      and non alcoholic steatohepatitis (NASH) in morbidly obese patients undergoing
      bariatric surgery and to identify risk factors associated with the disease
      spectrum. METHODS: Liver biopsy was performed in 60 patients who underwent
      bariatric surgery, after other causes of liver disease were excluded. Clinical,
      biochemical and histological features were evaluated. RESULTS: NAFLD was detected
      in fifty-seven patients (95%) of the sample and forty patients (66.7%) of the
      total sample met the criteria for NASH. Perisinusoidal fibrosis was only found in
      three (7.5%) patients with NASH. The gammaGT was an independent predictive factor
      associated with the degree of hepatic steatosis. The variables such as
      dyslipidemia and ALT were independently associated with the presence of Mallory's
      corpuscles with the following values, respectively, OR 0, 05, 95% CI 0.002 to
      0.75, P = 0.031 and OR 10, 99, 95% CI 1.44 to 83.93, P = 0.021. CONCLUSIONS: Non
      alcoholic fatty liver disease seems to be an obese-related condition with
      approximately half of asymptomatic morbidly obese patients having histological
      NASH. The gammaGT was an independent predictor of the degree of steatosis.

PMID- 24316748
TI  - A prospective study of venous hemodynamics and quality of live at least five
      years after varicose vein stripping.
AB  - PURPOSE: To assess venous hemodynamics and quality of life at lest five years
      after varicose vein stripping. METHODS: We conducted a prospective study with 39
      patients (63 limbs) with primary lower limbs varicose veins. Preoperatively, all
      patients were subjected to clinical evaluation, duplex ultrassound, air
      plethysmography (APG), and CIVIQ questionnaire of quality of life. By APG, venous
      filling index (VFI), ejection fraction (EF), and residual volume fraction (RVF)
      were determined. CIVIQ addresses four domains in course of 20 questions,
      including states of physical, social, and psychological well-being, and pain
      level. Varicose veins were treated by standard venous stripping. At least five
      years after surgery (77.9 +/- 10.9 months), patients were reassessed and had
      clinical examination, duplex ultrasound, APG, and CIVIQ repeated. No late follow
      up data was available for 24 patients. RESULTS: Preoperative and late
      postoperative VFI levels were similar, whereas EF (P=0.05) and RVF (P=0.01), as
      hemodynamic variables, significantly improved following surgery. In the late
      postoperative period, overall CIVIQ scores were significantly lower (P=0.005), as
      were scores in all four domains: pain (P=0.001), physical (P=0.007), social
      (P=0.008), and psychological (P= 0.05). CONCLUSION: In a small prospective
      cohort, improvements in venous hemodynamics and in quality of life of patients
      submitted to standard varicose veins stripping were maintained five years after
      the procedure.

PMID- 24316749
TI  - Comparative study of scientific publications in orthopedics journals originating
      from USA, Japan and China (2000-2012).
AB  - PURPOSE: To compare orthopedics publications from USA, Japan and China. METHODS:
      Scientific papers belong to ''Orthopedics'' category of Science Citation Index
      Expanded subject categories were retrieved from the "PubMed'' and ''Web of
      Knowledge'' online databases. RESULTS: In the field of orthopedics, the annual
      number increased significantly from 2000 to 2012 in the three countries
      (p<0.001). The share of articles increased significantly in China, but decreased
      significantly in Japan and USA (p<0.05). In 2012, USA contributed 35.3% of the
      total world output in orthopedics field and ranked 1st; Japan contributed 5.9%
      and ranked 4th; China contributed 5.2% and ranked 5th. Publications from USA had
      the highest accumulated IFs and the highest total citations of articles (USA >
      Japan > China, p<0.001). Average IF from USA was much higher than Japan and China
      (p<0.001). USA published the most articles in the top ten orthopedics journals
      (USA (14355) > Japan (1702) > China (487), p<0.01). CONCLUSION: Although China
      has undergone significant increase in annual number and percentage of scientific
      publication in orthopedics journals, it still lags far behind USA and Japan in
      the field of orthopedics in terms of quantity and quality.

PMID- 24316751
TI  - Quality and seasonal variation of rainwater harvested from concrete, asphalt,
      ceramic tile and green roofs in Chongqing, China.
AB  - There is an urgent requirement to examine the quality of harvested rainwater for
      potable and non-potable purposes, based on the type of roofing material. In this
      study, we examined the effect on the quality of harvested rainwater of
      conventional roofing materials (concrete, asphalt and ceramic tile roofs)
      compared with alternative roofing materials (green roof). The results showed that
      the ceramic tile roof was the most suitable for rainwater-harvesting applications
      because of the lower concentrations of leachable pollutants. However, in this
      study, the green roof was not suitable for rainwater harvesting applications. In
      addition, seasonal trends in water quality parameters showed that pollutants in
      roof runoff in summer and autumn were lower than those in winter and spring. This
      study revealed that the quality of harvested rainwater was significantly affected
      by the roofing material; therefore, local government and urban planners should
      develop stricter testing programs and produce more weathering resistant roofing
      materials to allow the harvesting of rainwater for domestic and public uses. 

PMID- 24316750
TI  - IL-17A is produced by breast cancer TILs and promotes chemoresistance and
      proliferation through ERK1/2.
AB  - The proinflammatory cytokine Interleukin 17A (hereafter named IL-17A) or IL-17A
      producing cells are elevated in breast tumors environment and correlate with poor
      prognosis. Increased IL-17A is associated with ER(-) or triple negative tumors
      and reduced Disease Free Survival. However, the pathophysiological role of IL-17A
      in breast cancer remains unclear although several studies suggested its
      involvement in cancer cell dissemination. Here we demonstrated that a subset of
      breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems
      mainly associated to ER(-) and triple negative/basal-like tumors. Isolation of
      tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that
      these cells secreted significant amounts of IL-17A. We further established that
      recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated
      ERK1/2 in human breast cancer cell lines thereby promoting proliferation and
      resistance to conventional chemotherapeutic agents such as docetaxel. We also
      confirmed here that recombinant IL-17A stimulates migration and invasion of
      breast cancer cells as previously reported. Importantly, TILs also induced tumor
      cell proliferation, chemoresistance and migration and treatment with IL-17A
      neutralizing antibodies abrogated these effects. Altogether these results
      demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a
      subset of breast cancers. Therefore, IL-17A appears as potential therapeutic
      target for breast cancer. 

PMID- 24316752
TI  - Multi-level participatory design of land use policies in African drylands: a
      method to embed adaptability skills of drylands societies in a policy framework.
AB  - The participatory modelling method described here focuses on how to enable
      stakeholders to incorporate their own perception of environmental uncertainty and
      how to deal with it to design innovative environmental policies. This "self
      design" approach uses role playing games and agent based modelling to let
      participants design their own conceptual framework, and so modelling supports, of
      issues. The method has a multi-scale focus I order to enable the whole multi
      scale Sahelian logic to be expressed and on the other hand to encourage the
      players to deal with possible region-wide changes implied by their "local" policy
      objectives. This multi-level participatory design of land use policies has been
      under experimentation in Senegal since 2008 in different local and national
      arenas. The process has resulted in the "self-design" of a qualitative and
      relatively simple model of Sahelian uncertainty, which can be played like a role
      playing game as well a computerized model. Results are shown in perceptible
      autonomous organisational learning at the local level. Participants were also
      able to incorporate their own ideas for new rules for access to resources. They
      designed innovative collective rules, organised follow up and monitoring of these
      new land uses. Moreover, meaningful ideas for environmental policies are
      beginning to take shape. This work raises the epistemological question of what is
      meant by the term "indigenous knowledge" in environmental management, ranging
      from knowledge based on practical experience being included in the scholar's
      framing of knowledge, to a legitimate local ability to contextualize and re
      arrange scientific expertise, to profoundly different worldviews which do not
      match ours. 

PMID- 24316754
TI  - Poly(N-vinyl caprolactam) grown on nanographene oxide as an effective nanocargo
      for drug delivery.
AB  - This study evaluated graphene oxide functionalized covalently with poly N-vinyl
      caprolactam (GO-PVCL) via in situ atomic transfer radical polymerization (ATRP),
      as a nano-cargo carrier for the efficient delivery of drugs into cells. Water
      soluble GO-PVCL exhibited excellent stability in physiological solutions. An anti
      cancer drug, camptothecin (CPT), was then loaded onto GO-PVCL with a high payload
      (20%) through pi-pi stacking and hydrophobic interactions, and its release could
      be controlled by varying the pH. PVCL grafted onto GO offers an additional
      advantage of targeted delivery according to temperature. GO-PVCL showed no
      obvious toxicity, whereas the CPT-loaded GO-PVCL showed high potency in killing
      cancer cells in vitro. The drug transportation mechanism was found to be energy
      dependent endocytosis. Overall, this study revealed GO-PVCL to be a promising
      drug delivery vector with high biocompatibility, solubility and stability in
      physiological solutions, and good payload capacity owing to its small size, low
      cost, large specific area, ready scalability, and useful non-covalent
      interactions. This material is expected to be a novel material propitious for
      biomedical applications. 

PMID- 24316753
TI  - Degree of methylation of ZAC1 (PLAGL1) is associated with prenatal and post-natal
      growth in healthy infants of the EDEN mother child cohort.
AB  - The ZAC1 gene, mapped to the 6q24 region, is part of a network of co-regulated
      imprinted genes involved in the control of embryonic growth. Loss of methylation
      at the ZAC1 differentially methylated region (DMR) is associated with transient
      neonatal diabetes mellitus, a developmental disorder involving growth retardation
      and diabetes in the first weeks of post-natal life. We assessed whether the
      degree of methylation of the ZAC1 DMR in leukocytes DNA extracted from cord blood
      is associated with fetal, birth and post-natal anthropometric measures or with C
      peptide concentrations in cord serum. We also searched for an influence of
      dietary intake and maternal parameters on ZAC1 DMR methylation. We found positive
      correlations between the ZAC1 DMR methylation index (MI) and estimated fetal
      weight (EFW) at 32 weeks of gestation, weight at birth and weight at one year of
      age (respectively, r = 0.15, 0.09, 0.14; P values = 0.01, 0.15, 0.03). However,
      there were no significant correlations between the ZAC1 DMR MI and cord blood C
      peptide levels. Maternal intakes of alcohol and of vitamins B2 were positively
      correlated with ZAC1 DMR methylation (respectively, r = 0.2 and 0.14; P = 0.004
      and 0.04). The influence of ZAC1 seems to start in the second half of pregnancy
      and continue at least until the first year of life. The maternal environment also
      appears to contribute to the regulation of DNA methylation. 

PMID- 24316755
TI  - A novel copper(II) complex as a nitric oxide turn-on fluorosensor: intracellular
      applications and DFT calculation.
AB  - We report, herein, the development of an easily synthesizable novel dansyl-based
      turn-on NO sensor L2. The UV-Vis titration data of L2 with Cu(2+) display a
      gradual increase in absorbance at 418 nm with [Cu(2+)], which were analyzed by
      using a non-linear least-squares computer-fit program yielding K = (1.16 +/-
      0.36) * 10(6) M(-1) and n = (1.28 +/- 0.03) indicating a 1 : 1 complexation. The
      ground state geometries of L2 as well as its complex [Cu(L2)Cl](+) (1) were
      optimized by DFT calculations which showed that in complex 1 the central metal
      ion is in distorted tetrahedral geometry with bond distances very close to those
      found in analogous Cu(2+) complexes. The fluorescence of L2 was dramatically
      quenched (~60-fold) through complexation with paramagnetic Cu(2+) to form
      [Cu(L2)Cl](+) in MeCN-H2O (9 : 1, v/v) at pH 7.2 in HEPES buffer, which on
      further treatment with Angeli's salt (Na2N2O3) restores its fluorescence property
      by ~15-fold due to the reduction of Cu(2+) to Cu(+) by NO generated in solution
      from Na2N2O3. The lifetime measurements displayed a substantial decrease in the
      lifetime of free ligand L2 (tau0 = 12 ns) on complexation with Cu(2+) (tau0 = 2.1
      ns). The detection limit of NO calculated by the 3sigma method gives a value of
      1.6 nM. The NO induced fluorescence enhancement of [Cu(II)(L2)Cl](+) was due to
      the reduction of [Cu(II)(L2)Cl](+) (1) to [Cu(I)(L2)](+) (2) and is supported by
      the disappearance of the d-d transition band at 850 nm as well as the X-band EPR
      signal of 1. The selective "turn on" fluorogenic behavior of L2 was examined on
      HeLa cells of human cervical cancer origin by fluorescence microscopy which
      showed very intense intracellular fluorescence that was strongly suppressed by
      the addition of Cu(2+) but it regains its fluorescence property on further
      incubation with Angeli's salt (Na2N2O3). The existence of [Cu(II)(L2)Cl](+) and
      [Cu(I)(L2)](+) in solution was confirmed by ESI-MS(+) (m/z) analysis. The effect
      of different biologically relevant cations and anions on the fluorescence
      property of L2 indicates that it was only the [Cu(II)(L2)Cl](+) which displayed
      high selectivity for NO, indicating its suitability for intracellular application
      without much worry about its cytotoxicity in a specified dose. 

PMID- 24316756
TI  - JNK contributes to temozolomide resistance of stem-like glioblastoma cells via
      regulation of MGMT expression.
AB  - While elimination of the cancer stem cell population is increasingly recognized
      as a key to successful treatment of cancer, the high resistance of cancer stem
      cells to conventional chemoradiotherapy remains a therapeutic challenge. O6
      methylguanine DNA methyltransferase (MGMT), which is frequently expressed in
      cancer stem cells of glioblastoma, has been implicated in their resistance to
      temozolomide, the first-line chemotherapeutic agent against newly diagnosed
      glioblastoma. However, much remains unknown about the molecular regulation that
      underlies MGMT expression and temozolomide resistance of glioblastoma cancer stem
      cells. Here, we identified JNK as a novel player in the control of MGMT
      expression and temozolomide resistance of glioblastoma cancer stem cells. We
      showed that inhibition of JNK, either pharmacologically or by RNA interference,
      in stem-like glioblastoma cells derived directly from glioblastoma tissues
      reduces their MGMT expression and temozolomide resistance. Importantly,
      sensitization of stem-like glioblastoma cells to temozolomide by JNK inhibition
      was dependent on MGMT expression, implying that JNK controls temozolomide
      resistance of stem-like glioblastoma cells through MGMT expression. Our findings
      suggest that concurrent use of JNK inhibitors with temozolomide may be a rational
      therapeutic approach to effectively target the cancer stem cell population in the
      treatment of glioblastoma. 

PMID- 24316757
TI  - Innate immune cells in transplantation.
AB  - PURPOSE OF REVIEW: To examine the recent literature on the role of innate cells
      in immunity to transplanted tissue. It specifically addresses the impact of
      monocytes/macrophages, neutrophils, natural killer cells, and platelets. RECENT
      FINDINGS: Current research indicates that innate immunity plays a dual role in
      response to transplanted tissue with the ability to either facilitate rejection
      or promote tolerance. Intriguingly, some of these cells are even capable of
      reacting to allogeneic cells, a feature usually only attributed to cells of the
      adaptive immune system. SUMMARY: This review highlights the new therapeutic
      targets in the innate immune system that may be useful in the treatment of
      transplant recipients. It also emphasizes the need to use caution in exploring
      these new therapeutics.

PMID- 24316758
TI  - Antibody-mediated graft injury: complement-dependent and complement-independent
      mechanisms.
AB  - PURPOSE OF REVIEW: Antibody-mediated rejection (AMR) is emerging as the leading
      cause of chronic rejection and allograft failure. Traditionally, the mechanisms
      of graft injury mediated by donor-specific antibodies beyond complement
      activation were not well appreciated. However, an evolving paradigm of Fc
      independent antibody functions, along with clinical recognition of C4d-negative
      AMR, has increased awareness of the action of antibodies leading to endothelial
      activation and dysfunction. RECENT FINDINGS: Herein, we address current clinical
      trends, including the signature of microvascular inflammation in biopsies of
      grafts undergoing AMR, the prevalence of antibodies to human leukocyte antigen
      class II DQ locus (HLA-DQ) and non-HLA targets, and the functional
      characterization of HLA immunoglobulin G (IgG) subclasses and complement-fixing
      capacity. We also discuss recent experimental evidence revealing new mechanisms
      of endothelial and smooth muscle cell activation by HLA antibodies, which may
      contribute to vascular inflammation and chronic rejection. Finally, we touch upon
      novel discoveries of the interplay between antibodies, the complement system, and
      CD4 T-cell-mediated alloimmunity. SUMMARY: The current literature suggests that,
      although complement-fixing antibodies may have some prognostic value for graft
      outcome, complement-independent mechanisms of graft injury are increasingly
      relevant. Therapeutic strategies, which target endothelial activation induced by
      antibodies may ameliorate vascular inflammation and mononuclear cell infiltration
      characteristic of AMR.

PMID- 24316760
TI  - Life after pancreas transplantation: reversal of diabetic lesions.
AB  - PURPOSE OF REVIEW: Recipients of pancreas transplantation bear the burden of
      chronic complications of diabetes, both microvascular and macrovascular. Pancreas
      transplantation provides the most effective method of glycemic and metabolic
      control. As transplantation provides immediate relief from acute complications of
      diabetes, the impact of a successful transplant on long-term complications is the
      focus of this review. RECENT FINDINGS: It is increasingly recognized that a
      successful pancreas transplant may slow, stabilize, or ameliorate the progression
      of macrovascular and microvascular complications of diabetes. New understanding
      of the genetic and epigenetic mechanisms and pathophysiology of diabetic
      complications has provided new data potentially useful for prospectively studying
      the effect of pancreas transplant on chronic complications of diabetes. SUMMARY:
      Earlier correction of diabetes by pancreas transplantation decreases chronic
      complications. Refinements in the understanding of the tissue targets of diabetes
      complications and new diagnostic and imaging tools to measure them may prove
      useful in further studying the impact of pancreas transplantation on chronic
      complications of diabetes.

PMID- 24316759
TI  - Dendritic cells of myeloid lineage: the masterminds behind acute allograft
      rejection.
AB  - PURPOSE OF REVIEW: Advances in surgery, patient management, and pharmacologic
      immunosuppression have reduced the incidence of acute allograft rejection.
      However, generation of therapies to promote donor-specific immunosuppression with
      minimal side-effects has proved to be a difficult task. To some extent, this is
      because of our limited knowledge on how Ag-presenting cells (APCs) like dendritic
      cells initiate and maintain the antidonor response in vivo. Herein, we link the
      classic concepts on the role of donor's dendritic cells as passenger leukocytes
      with the state-of-the-art findings in the field. RECENT FINDINGS: Numerous
      studies are starting to unveil the plethora of mediators and interactions with
      leukocytes that trigger maturation of donor's dendritic cells in the grafts. The
      concept that donor's dendritic cells migrate from the grafts to secondary
      lymphoid organs to prime T cells has been challenged in murine models of lung or
      intestine transplantation, in which T cells can also be primed in the allograft.
      Increasing evidence suggests that recipient's dendritic cells present donor's
      intact major histocompatibility complex (MHC) molecules in lymphoid organs and
      that they infiltrate the grafts. SUMMARY: A more complete understanding of the
      role of dendritic cells in allosensitization will help to develop better
      dendritic cell-based therapies to achieve the final goal of promoting donor
      specific immunosuppression.

PMID- 24316761
TI  - Roles of Toll-like receptors in transplantation.
AB  - PURPOSE OF REVIEW: Beyond their crucial role in host defence against invading
      pathogens, Toll-like receptors (TLRs) are now known to be key mediators of the
      'sterile' innate immune response triggered by tissue injury. Here, we will review
      recent evidence examining the role of TLRs in determining the fate of the
      transplanted organ. RECENT FINDINGS: Experimental studies have delineated a
      crucial role for TLRs in the pathogenesis of ischaemia-reperfusion injury (IRI).
      Following transplantation, experimental models and observational human studies
      have confirmed TLRs as mediators of IRI but also suggest that TLRs modify the
      subsequent adaptive alloimmune response, which determines whether an organ is
      rejected or accepted. SUMMARY: As a key determinant of organ damage following
      ischaemia-reperfusion and as a modulator of the adaptive alloimmune response, we
      propose that TLR-mediated innate immune responses represent a potential
      therapeutic target to improve organ outcomes following transplantation.

PMID- 24316762
TI  - Mechanisms of rejection: role of complement.
AB  - PURPOSE OF REVIEW: To provide the reader with an up-to-date comprehensive review
      of recent findings that highlight advances describing how proteins of the
      complement cascades contribute to the pathogenesis of solid organ rejection. The
      review is focussed mainly on renal transplantation. RECENT FINDINGS: Of note are
      recent advances in elucidating the interactions between anaphylatoxins and their
      receptors in organ transplantation; there is evidence of direct engagement of
      C5aR on donor tubules and in addition, mechanisms by which the allostimulatory
      capacity of dendritic cells is modulated by complement are more fully understood.
      Activation of the lectin pathway is increasingly implicated in allograft
      rejection and the role of complement in modulating regulatory T cells is being
      vigorously investigated. As an alternative to systemic complement inhibition,
      there is continued focus on the design of targeted anti-complement therapies,
      directed to the donor organ. SUMMARY: Complement has evolved as the first line of
      defence against pathogens, employing well defined effector mechanisms to rapidly
      remove infectious material. However, complement effector mechanisms are also
      triggered during inflammation associated with solid organ transplantation. Hence,
      complement has a significant role in mediating donor organ injury during both the
      initial ischaemia/reperfusion phase and the subsequent adaptive immune responses.
      Research on mechanisms of complement-mediated injury in transplantation provide a
      basis for the development of therapies that are aimed at transiently blocking
      complement activation at the site of injury, whereas leaving systemic anti
      bacterial complement effector mechanisms intact.

PMID- 24316763
TI  - [Breast cancer and axillary area: state of the art and perspectives].
AB  - A therapeutic surgical de-escalation has been observed since many years with an
      actual prolongation for axillary lymph node area treatment. Axillary lymph node
      dissection (ALND) omission has been studied before and after validation of
      sentinel node (SN) biopsy procedure. A non-inferiority of ALND omission has been
      reported in case of non-involved SN. ALND omission has been studied in case of SN
      involvement without consensus in relation with scientific level of proof and with
      selective indications. The purpose of this work is to make a synthesis of the
      experiences on this subject then to envisage the current and future perspectives.

PMID- 24316764
TI  - Liquid chromatography-tandem mass spectrometry assay for therapeutic drug
      monitoring of the tyrosine kinase inhibitor, midostaurin, in plasma from patients
      with advanced systemic mastocytosis.
AB  - We developed and validated quantitative bioanalytical liquid chromatography
      tandem mass spectrometry assay for the protein kinase inhibitor, midostaurin.
      Plasma samples were pre-treated using a protein precipitation with methanol
      containing midostaurin-d5 as an internal standard. After centrifugation, 5MUL of
      the supernatant was injected into the chromatographic system. The system
      consisted of a 3.5MUm particle bonded octadecyl silica column, with gradient
      elution using a mixture of 0.1% (v/v) formic acid in acetonitrile and 10mM
      ammonium formate in water with 0.1% formic acid. The analyte was quantified using
      the selected reaction-monitoring mode of a triple quadrupole mass spectrometer
      equipped with a heated electrospray interface. The assay was validated in a 75
      2500ng/mL calibration range. For quality control, within-day and between-day
      precisions were 1.2-2.8%, and 1.2-6.9%, respectively. The beta-expectation
      tolerance limit (accuracy) met the limits of acceptance +/-15% (+/-20% for the
      LLQ). The drug was sufficiently stable under all relevant analytical conditions.
      The assay has successfully been used to assess drug levels for therapeutic drug
      monitoring in patients presenting advanced systemic mastocytosis and treated with
      the promising midostaurin. 

PMID- 24316765
TI  - Tar heel footprints in health care: Kerry Crandall, MS, CGC.

PMID- 24316766
TI  - The relation of race and type of health insurance to long-term risk of mortality
      among lung cancer patients in rural Eastern North Carolina.
AB  - BACKGROUND: Black patients with lung cancer have a higher mortality rate than do
      their white counterparts. Differences in insurance coverage, demographic
      characteristics, and treatment profiles may explain this disparity. The purpose
      of this study was to compare the longterm risk of mortality of black lung cancer
      patients with that of white lung cancer patients, by insurance type. METHODS:
      Patients who were diagnosed with lung cancer in Eastern North Carolina and
      treated at the Leo Jenkins Cancer Center between 2001 and 2010 were included in
      this study. A Cox regression model was used to compare the risk of mortality of
      black patients with that of white patients. RESULTS: A total of 2,351 lung cancer
      patients (717 black and 1,634 white) were treated at the Leo Jenkins Cancer
      Center during the study period. Independent of age and sex, black patients with
      lung cancer were observed to die sooner than their white counterparts (hazard
      ratio = 1.2; 95% confidence interval, 1.04-1.3; P = .0070). However, this
      difference was not statistically significant after controlling for and
      stratifying by insurance type. LIMITATIONS: Residual confounding and the
      misclassification of some variables could have biased estimated study effects.
      CONCLUSION: The racial disparity in lung cancer mortality observed in Eastern
      North Carolina is no longer apparent after health insurance type is accounted
      for.

PMID- 24316767
TI  - Community perceptions of genomic research: implications for addressing health
      disparities.
AB  - BACKGROUND: Increasing the engagement of racial and ethnic minorities in genomic
      research may help alleviate health disparities. This paper examines community
      perceptions of the relationships between race, genes, environment, and health
      disparities, and it discusses how such perceptions may influence participation in
      genomic research. METHODS: We conducted semi-structured interviews with 91
      African American, Latino, and white lay community members and community leaders
      in North Carolina. Using constant comparison methods, we identified, compared,
      and developed linkages between conceptual categories and respondent groups.
      RESULTS: Participants described gene-environment interactions as contributing to
      group differences in health outcomes, expressed the belief that genetic
      predisposition to disease differs across groups, and said that social conditions
      trigger group-level genetic differences and create poorer health outcomes among
      African Americans. LIMITATIONS: Given the regional presence of major research
      institutions and the relatively high education level of many participants, this
      sample may not reflect the perspectives of those most disparately affected by
      health disparities. CONCLUSIONS: Members from multiple community sectors share
      perceptions and may respond to similar approaches when attempts are made to
      increase participation in genomic research. Researchers may inadvertently fuel
      the perception that health disparities experienced by minorities are rooted in
      the shared genomes of a particular group as distinct from those of other groups.
      The way researchers use race and ethnicity in recruitment, analysis, and
      communication of research findings inaccurately implies that there are genetic
      differences between races, when categories of social experience or ancestry may
      more accurately characterize health differences. Understanding these issues is
      crucial to designing effective community engagement strategies, recruitment
      plans, and messages about genomic research, which could ultimately help to lessen
      health disparities.

PMID- 24316768
TI  - From Mendel to the Human Genome Project.

PMID- 24316769
TI  - Personalized health care in 2013: a status report on the impact of genomics.
AB  - This issue of the NCMJ describes the impact that genomics has had on the practice
      of medicine in the decade since the full sequencing of the human genome was
      completed in 2003. Specifically, it reports on how genomics is affecting health
      care delivery, describes the concept of personalized health care, and discusses
      the role that genomics plays in such care. The commentaries and sidebars that
      follow highlight the opportunities and challenges of bringing genomics into
      clinical practice. Reading these articles will hopefully give clinicians and
      others a better understanding of the benefits and limitations of genomic
      technologies. Emerging capabilities, resulting in part from genomic research, are
      providing an opportunity to move health care from a reactive, disease-focused
      model to one that is personalized, predictive, proactive, precise, and patient
      centered. Genomics and related technologies have already changed many approaches
      to care, particularly in the field of oncology, and I believe they will help to
      transform our overall approach to the delivery of health care. With the rapidly
      accumulating capabilities being developed and the focus on patient-centered and
      personalized care, I expect that the practice of medicine will become proactive
      and personalized within the next decade.

PMID- 24316770
TI  - Pharmacogenomic testing and the prospect of individualized treatment.
AB  - Pharmacogenomics offers the hope of greater individualization of treatment.
      Therapies that exemplify the promise of pharmacogenomics include anticoagulation
      with warfarin and the use of antiplatelet medications (eg, clopidogrel) for
      secondary prevention after acute coronary syndrome. Good evidence of clinical
      utility must be obtained before pharmacogenomic testing is widely implemented. 

PMID- 24316771
TI  - Cystic fibrosis: a model for personalized genetic medicine.

PMID- 24316772
TI  - Pros and cons of screening for BRCA mutations.

PMID- 24316773
TI  - Educating future providers of personalized medicine.

PMID- 24316774
TI  - Direct-to-consumer genomic testing offers little clinical utility but appears to
      cause minimal harm.
AB  - Direct-to-consumer genomic testing is available to anyone willing to pay for it.
      We investigated the reliability and reproducibility of such testing by sending
      DNA samples to 2 popular companies and by reviewing current literature on this
      topic. The concerns that were initially raised about direct-to- consumer genomic
      testing still seem valid.

PMID- 24316775
TI  - Direct-to-consumer nutrigenomic testing: is it valuable in spite of its
      limitations?

PMID- 24316776
TI  - The NCGENES project: exploring the new world of genome sequencing.
AB  - Massively parallel sequencing (MPS) is now a clinical reality, promising improved
      diagnosis, targeted therapies, and population-based screening. To realize the
      potential of genomics, we must learn how to apply this technology optimally. The
      NCGENES project is designed to address several challenges that must be overcome
      in order to integrate MPS into clinical care. 

PMID- 24316777
TI  - Crowdsourcing to define the clinical actionability of incidental findings of
      genetic testing.

PMID- 24316778
TI  - Genetic epidemiology: the potential benefits and challenges of using genetic
      information to improve human health.
AB  - Genetic epidemiology has the potential to significantly affect human health. This
      commentary examines major developments in the field's history, promising avenues
      of research, and possible challenges faced by genetic epidemiologists. 

PMID- 24316779
TI  - Integrating personalized genomic medicine into routine clinical care: addressing
      the social and policy issues of pharmacogenomic testing.
AB  - The provision of personalized genomic medicine presents significant policy
      challenges, such as ensuring equitable patient access to testing, preparing
      clinicians to manage genomic results, justifying test reimbursement, sharing
      genomic information for patient care, and protecting patients against misuse of
      genetic information. 

PMID- 24316780
TI  - Update on newborn screening.
AB  - Since phenylketonuria was first screened for in the 1960s, newborn screening has
      expanded to include more than 30 conditions. This commentary provides an update
      on newborn screening, including the follow-up of abnormal findings, the
      limitations of such screening, and the ethical questions that screening raises. 

PMID- 24316781
TI  - An overview of prenatal genetic screening and diagnostic testing.
AB  - Although prenatal genetic testing has been available for more than 3 decades, the
      number of conditions that can be detected has increased exponentially over the
      past decade. This commentary describes currently available prenatal genetic
      screening and diagnostic tests and explores practical and social considerations
      related to prenatal testing. 

PMID- 24316782
TI  - Ethical concerns about genetic testing and screening.
AB  - Many of the ethical concerns raised by genetic testing and screening relate to
      accuracy, cost, and confidentiality. Perhaps the most serious worry-one that is
      not without merit-is that the new genomics is a disguised version of the old
      eugenics. On balance, however, genetic testing and screening seem to be in
      society's best interests. 

PMID- 24316783
TI  - Gene therapy: the promise of a permanent cure.
AB  - Gene therapy offers the possibility of a permanent cure for any of the more than
      10,000 human diseases caused by a defect in a single gene. Among these diseases,
      the hemophilias represent an ideal target, and studies in both animals and humans
      have provided evidence that a permanent cure for hemophilia is within reach. 

PMID- 24316784
TI  - Is genetic testing of value in predicting and treating obesity?
AB  - Obesity is a multifactorial disease resulting from the interaction between
      genetic factors and lifestyle. Identification of rare genetic variations with
      strong effects on obesity has been useful in diagnosing and designing
      personalized therapy for early-onset or syndromic obesity. However, common
      variants identified in recent genome-wide association studies have limited
      clinical value. 

PMID- 24316785
TI  - Epigenetic considerations in medicine.
AB  - Epigenetic modifications are gene regulatory mechanisms that allow rapid
      adaptation to the environment. These mitotically stable and meiotically heritable
      changes are sensitive to environmental conditions especially during developmental
      periods, and they are essential to understanding how information in the DNA
      sequence is utilized. Recent research in this area has led to excitement and
      questions about medical applications of epigenetics. 

PMID- 24316786
TI  - North Carolina's Genetic Counseling Program: empowering families with genetic
      knowledge.

PMID- 24316787
TI  - Mobile mammography: driving preventive care for underserved women.

PMID- 24316788
TI  - Meeting the perinatal care challenges of Eastern North Carolina.

PMID- 24316790
TI  - Otolaryngology: "It's all Greek to me".
AB  - This study explores the origins and evolution of the specialty name for what is
      now primarily known in the English-speaking world as otolaryngology-head and neck
      surgery. This appellation is the longest and least pronounceable of all medical
      specialties. While it is reasonably well understood among medical professionals,
      surveys show that only a small fraction of health consumers understand its
      meaning. The ideal medical specialty name should have a meaning recognizable to a
      large segment of the public, be easily pronounceable, be reasonably short, and
      serve to communicate the type of illnesses treated. The cumbersomeness of the
      specialty name has led to nearly universal use of informal substitutes, which do
      not covey the scope of contemporary practice (e.g., ear, nose, and throat) and to
      abbreviations (e.g., ENT, ORL, OHNS). Based on the commercial experience, it is
      clear that shorter is better. The authors advocate that dialog be opened, guided
      by the experience from instances of successful corporate rebranding, to consider
      possible alternatives.

PMID- 24316789
TI  - Degradation and transformation products of acetaminophen in soil.
AB  - Acetaminophen is the most widely used human medicine. Trace levels of
      acetaminophen are frequently detected in treated wastewater and the impacted
      surface or groundwater resources. However, even though soil is a primary
      receiving compartment, the fate of acetaminophen in soil is poorly known,
      including in particular the potential for the formation of incomplete degradation
      products that may have altered biological activity and mobility. In this study,
      using both (14)C-labeling and LC-MS/MS techniques, we evaluated the dissipation
      routes and transformation pathways of acetaminophen in soils under a range of
      conditions. Throughout 120-d aerobic incubation, up to 17.0 +/- 0.8% of (14)C
      acetaminophen was mineralized, but mineralization was greatly inhibited after
      sterilization or amendment of biosolids. Immediately after treatment, the
      majority of (14)C-residue became non-extractable or bound, with the level
      accounting for 73.4-93.3% of the applied amount at the end of incubation. A total
      of 8 intermediates were identified, including 3-hydroxyacetaminophen,
      hydroquinone, 1, 4-benzoquinone, N-acetyl-p-benzoquinone imine, p-acetanisidide,
      4-methoxyphenol, 2-hexenoic acid, and 1, 4-dimethoxybenzene. Mineralization and
      rapid conversion to bound residues suggest that acetaminophen is quickly
      detoxified in soil, decreasing the potential for off-site transport such as
      leaching or runoff. On the other hand, the formation of a large number of
      degradation intermediates, and their potential biological activity, may pose
      unknown risks, such as accumulation into edible plants. This risk warrants
      further investigation. 

PMID- 24316791
TI  - Management of obstructive sleep apnea in the indigent population: a deviation of
      standard of care?
AB  - Comprehensive management of patients with obstructive sleep apnea (OSA) typically
      is managed best via a multidisciplinary approach, involving otolaryngologists,
      sleep psychologists/psychiatrists, pulmonologists, neurologists, oral surgeons,
      and sleep trained dentists. By utilizing these resources, one could fashion a
      treatment individualized to the patient, giving rise to the holistic phrase of
      "personalized medicine." Unfortunately, in situations and environments with
      limited resources, the treatment options in an otolaryngologist's armamentarium
      are restricted--typically to continuous positive airway pressure (CPAP) versus
      sleep surgery. However, a recent patient encounter highlighted here shows how a
      hospital's reimbursement policy effectively dictated a patient's medical
      management to sleep surgery. This occurred although the current gold standard for
      the initial treatment of OSA is CPAP. Changing the course of medical/surgical
      management by selectively restricting funding is a cause of concern, especially
      when it promotes patients to choose a treatment option that is not considered the
      current standard of care.

PMID- 24316792
TI  - Clothing hanger injuries: pediatric head and neck traumas in the United States,
      2002-2012.
AB  - OBJECTIVE: To discuss pediatric clothing hanger injuries and review the National
      Electronic Injury Surveillance System to elucidate frequency and promote
      increased public awareness among pediatric otolaryngologists. STUDY DESIGN: Cross
      sectional analysis of a national database. STUDY SETTING: National Electronic
      Injury Surveillance System Database. METHODS: A retrospective review of the
      National Electronic Injury Surveillance System provided a nationally weighted
      sampling estimate of 394 pediatric incident reports involving clothing hangers.
      Each incident report was analyzed for impalement, facial laceration, and
      contusion injuries to the mouth, face, and head. In addition, hospital
      disposition and location of the described incident were also obtained. RESULTS:
      Upon review of the National Electronic Injury Surveillance System, incident rates
      of pediatric oral impalement (95% confidence interval [CI], 0.10-0.41), facial
      laceration (95% CI, 0.22-0.41), and facial abrasion injuries (95% CI, 0.15-0.44)
      frequently involved the metal clothing hanger design. In addition, most of the
      reported injuries occurred within the home and involved lacerations to the oral
      cavity. CONCLUSIONS: This is the first multiyear, nationally representative study
      to analyze clothing hanger injuries in the pediatric population. We demonstrate
      that these injuries occur more frequently than the medical literature currently
      reports and also elucidate that children are more likely to obtain laceration
      injuries by metal clothing hangers within the home. Furthermore, we provide a
      recommendation for standardization of the National Electronic Injury Surveillance
      System such that product safety analysis may occur and reduce further pediatric
      incidents.

PMID- 24316793
TI  - Use of the supraclavicular artery island flap for reconstruction of cervicofacial
      defects.
AB  - OBJECTIVE: To describe the supraclavicular artery island (SAI) flap as an
      alternative flap for reconstruction of cervicofacial defects. STUDY DESIGN: Case
      series with chart review. SETTING: Academic, tertiary referral center. SUBJECTS
      AND METHODS: Twenty-two patients with defects of the face, temporal bone, and
      neck were reconstructed with an SAI flap. Each defect was deemed unsuitable for
      primary or local flap closure and would require regional or free tissue transfer.
      Outcome measures included size and location of the defect, time to raise the
      flap, flap size and viability, and complications. Mean follow-up was 7.4 months
      (range, 1-31 months). Statistical analysis was performed using SAS 9.1 (SAS
      Institute, Cary, North Carolina). RESULTS: Defects of the cervical skin (n = 10),
      face (n = 8), and temporal bone (n = 4) were reconstructed. Mean flap dimensions
      were 6.1 cm (range, 5-7 cm) wide and 21.8 cm (range, 16-28 cm) long. The proximal
      portion of the flap was deepithelialized to match the defect, resulting in a mean
      skin paddle length of 9.6 cm (range, 5-18 cm). Minor donor site dehiscence
      occurred in 3 patients. Partial skin flap necrosis occurred in 2 patients, while
      1 patient had complete loss of the skin paddle. There was no statistical
      correlation between flap necrosis and flap length (P = .3, chi(2)) or defect
      location (P = .13, chi(2)). CONCLUSION: The SAI flap is a viable alternative to
      cervicofacial advancement or microvascular reconstruction of cervicofacial
      defects in select cases. This flap is reliable, easy to harvest, and versatile,
      and it provides a good color match for cervicofacial defects.

PMID- 24316794
TI  - In vitro antitumor effect of sodium butyrate and zoledronic acid combined with
      traditional chemotherapeutic drugs: a paradigm of synergistic molecular targeting
      in the treatment of Ewing sarcoma.
AB  - Histone deacetylase inhibitors and bisphosphonates have a promising future in the
      treatment of cancer as targeted anticancer drugs, particularly when used together
      or in combination with other cytotoxic agents. However, the effects of these
      combined treatments have not yet been systematically evaluated in Ewing sarcoma.
      The in vitro effects on cellular proliferation, viability and survival were
      investigated in two Ewing sarcoma cell lines, SK-ES-1 and RD-ES. The cell lines
      were treated with sodium butyrate, a histone deacetylase inhibitor and zoledronic
      acid, a bisphosphonate, alone, together or in combination with chemotherapeutic
      drugs recommended for clinical treatment of Ewing sarcoma. The data demonstrated
      that the combination of sodium butyrate and zoledronic acid had a synergistic
      cytotoxic effect at 72 h following treatment, persisting for 10-14 days post
      treatment, in both cell lines tested. All combinations between sodium butyrate or
      zoledronic acid and the traditional antineoplastic drugs (doxorubicin, etoposide
      and vincristine) demonstrated a synergistic cytotoxic effect at 72 h in SK-ES-1
      and RD-ES cells, except for the combinations of sodium butyrate with vincristine
      and of zoledronic acid with doxorubicin, which showed only an additive effect in
      RD-ES cell lines as compared to each agent alone. These acute effects observed in
      both Ewing sarcoma cell lines were confirmed by the clonogenic assay. The present
      data suggest that combining histone deacetylase inhibitors and bisphosphonates
      with traditional chemotherapeutic drugs is a promising therapeutic strategy for
      the treatment of Ewing sarcoma, and provides a basis for further studies in this
      field.

PMID- 24316795
TI  - Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time
      and position division.
AB  - Where and when cells divide are fundamental questions. In rod-shaped fission
      yeast cells, the DYRK-family kinase Pom1 is organized in concentration gradients
      from cell poles and controls cell division timing and positioning. Pom1 gradients
      restrict to mid-cell the SAD-like kinase Cdr2, which recruits Mid1/Anillin for
      medial division. Pom1 also delays mitotic commitment through Cdr2, which inhibits
      Wee1. Here, we describe quantitatively the distributions of cortical Pom1 and
      Cdr2. These reveal low profile overlap contrasting with previous whole-cell
      measurements and Cdr2 levels increase with cell elongation, raising the
      possibility that Pom1 regulates mitotic commitment by controlling Cdr2 medial
      levels. However, we show that distinct thresholds of Pom1 activity define the
      timing and positioning of division. Three conditions-a separation-of-function
      Pom1 allele, partial downregulation of Pom1 activity, and haploinsufficiency in
      diploid cells-yield cells that divide early, similar to pom1 deletion, but
      medially, like wild-type cells. In these cells, Cdr2 is localized correctly at
      mid-cell. Further, Cdr2 overexpression promotes precocious mitosis only in
      absence of Pom1. Thus, Pom1 inhibits Cdr2 for mitotic commitment independently of
      regulating its localization or cortical levels. Indeed, we show Pom1 restricts
      Cdr2 activity through phosphorylation of a C-terminal self-inhibitory tail. In
      summary, our results demonstrate that distinct levels in Pom1 gradients delineate
      a medial Cdr2 domain, for cell division placement, and control its activity, for
      mitotic commitment. 

PMID- 24316796
TI  - Co6(MU3-OH)6 cluster based coordination polymer as an effective heterogeneous
      catalyst for aerobic epoxidation of alkenes.
AB  - A new hexaprismane Co(II)6(MU3-OH)6 cluster-based three-dimensional coordination
      polymer ({Co(MU3-OH)(HCOO)0.72(CH3COO)0.28}n, Co6-CP) was successfully
      synthesized and characterized with single-crystal XRD, IR spectra, TGA spectra
      and elemental analysis. Co6-CP was used as an effective heterogeneous catalyst
      for the aerobic epoxidation of various alkenes. For the catalytic epoxidation of
      trans-stilbene, the conversion and selectivity towards the epoxide reached 98.6
      and 98.0%, respectively. Also, an average TOF of 22 h(-1) was obtained for the
      reaction. The results indicated that Co6-CP displayed excellent aerobic
      epoxidation activity among the reported coordination polymer materials, even
      rivaling the traditional heterogeneous cobalt catalysts. The influence of the
      reaction parameters such as temperature and oxygen flow rate for the epoxidation
      of the trans-stilbene were also studied in detail.

PMID- 24316797
TI  - Detection of free and covalently bound microcystins in different tissues (liver,
      intestines, gills, and muscles) of rainbow trout (Oncorhynchus mykiss) by liquid
      chromatography-tandem mass spectrometry: method characterization.
AB  - So far only a few publications have explored the development of extraction
      methods of cyanotoxin extracted from complex matrices. With regard to
      cyanobacterial microcystins (MCs), the data on the contamination of the flesh of
      aquatic organisms is hard to compare and very limited due to the lack of
      validated methods. In recent years, evidence that both free and bound fractions
      of toxin are found in these tissues has highlighted the need to develop effective
      methods of quantification. Several techniques do exist, but only the Lemieux
      oxidation has so far been used to investigate complex tissue matrices. In this
      study, protocols based on the Lemieux approach were adapted for the quantitative
      chemical analysis of free MC-LR and MMPB derived from bound toxin in the tissues
      of juvenile trout gavaged with MC-LR. Afterwards, the NF V03 110 guideline was
      used to characterize the protocols elaborated and evaluate their effectiveness. 

PMID- 24316798
TI  - Toxicity of ionic liquids to Clostridium sp. and effects on uranium biosorption.
AB  - As green solvents ionic liquids (ILs) show high potential in nuclear industry for
      extraction and purification of actinides. However, to date relatively little
      information has been gained on ILs application in microbial processes, for
      example biosorption of radionuclides. We investigated the effects of three ILs, 1
      butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), N-ethylpyridinium
      trifluoroacetate (EtPyCF3COO) and N-ethylpyridinium tetrafluoroborate (EtPyBF4)
      on the growth and biosorption of uranium by Clostridium sp. The ILs affected the
      growth of the bacterium as evidenced by decreases in optical density, total gas
      production, and organic acids production from glucose metabolism. The IC50-48h of
      three ILs decreased in the order of BMIMPF6 (8.26mM)>EtPyBF4 (7.04mM)>EtPyCF3COO
      (4.05mM). Uranium biosorption by the bacterial cells decreased by 75% in the
      presence of 1% (v/v) BMIMPF6 and by about 90% with 1% (v/v) EtPyBF4 or
      EtPyCF3COO, in comparison to the control without ILs. The diminished biosorption
      may be attributed to the membrane damages induced by EtPyBF4 and EtPyCF3COO,
      which can be visualized by Transmission Electron Microscope (TEM) analysis.
      Energy-dispersive X-ray spectroscopy (EDS) analysis revealed the accumulation of
      uranium inside peripheral membrane of the cells exposed to uranium alone or with
      BMIMPF6, while little or no accumulation was observed in the presence of EtPyBF4
      and EtPyCF3COO. These results imply that potential toxicity of ILs towards
      microorganisms is a particularly important issue in limiting its biotechnological
      applications. 

PMID- 24316799
TI  - Modeling of H2S migration through landfill cover materials.
AB  - The emission of H2S from landfills in the United States is an emergent problem
      because measured concentrations within the waste mass and in ambient air have
      been observed at potentially unsafe levels for on-site workers and at levels that
      can cause a nuisance and potentially deleterious health impacts to surrounding
      communities. Though recent research has provided data on H2S concentrations that
      may be observed at landfills, facility operators and landfill engineers have
      limited predictive tools to anticipate and plan for potentially harmful H2S
      emissions. A one-dimensional gas migration model was developed to assist
      engineers and practitioners better evaluate and predict potential emission levels
      of H2S based on four factors: concentration of H2S below the landfill surface
      (C0), advection velocity (v), H2S effective diffusion coefficient (D), and H2S
      adsorption coefficient of landfill cover soil (MU). Model simulations indicated
      that H2S migration into the atmosphere can be mitigated by reducing H2S diffusion
      and advection or using alternative cover soils with a high H2S adsorption
      coefficient. Laboratory column experiments were conducted to investigate the
      effects of the four parameters on H2S migration in cover soils and to calculate
      the adsorption coefficient of different cover materials. The model was validated
      by comparing results with laboratory column experiments. Based on the results,
      the laboratory column provides an effective way to estimate the H2S adsorption
      coefficient, which can then be incorporated into the developed model to predict
      the depth of cover soil required to reduce emitted H2S concentrations below a
      desired level. 

PMID- 24316800
TI  - Laboratory and pilot-scale bioremediation of pentaerythritol tetranitrate (PETN)
      contaminated soil.
AB  - PETN (pentaerythritol tetranitrate), a munitions constituent, is commonly
      encountered in munitions-contaminated soils, and pose a serious threat to aquatic
      organisms. This study investigated anaerobic remediation of PETN-contaminated
      soil at a site near Denver Colorado. Both granular iron and organic carbon
      amendments were used in both laboratory and pilot-scale tests. The laboratory
      results showed that, with various organic carbon amendments, PETN at initial
      concentrations of between 4500 and 5000mg/kg was effectively removed within 84
      days. In the field trial, after a test period of 446 days, PETN mass removal of
      up to 53,071mg/kg of PETN (80%) was achieved with an organic carbon amendment
      (DARAMEND) of 4% by weight. In previous laboratory studies, granular iron has
      shown to be highly effective in degrading PETN. However, for both the laboratory
      and pilot-scale tests, granular iron was proven to be ineffective. This was a
      consequence of passivation of the iron surfaces caused by the very high
      concentrations of nitrate in the contaminated soil. This study indicated that low
      concentration of organic carbon was a key factor limiting bioremediation of PETN
      in the contaminated soil. Furthermore, the addition of organic carbon amendments
      such as the DARAMEND materials or brewers grain, proved to be highly effective in
      stimulating the biodegradation of PETN and could provide the basis for full-scale
      remediation of PETN-contaminated sites. 

PMID- 24316801
TI  - Toxicity formation and distribution in activated sludge during treatment of N,N
      dimethylformamide (DMF) wastewater.
AB  - The organic toxicity of sludge in land applications is a critical issue; however,
      minimal attention has been given to the mechanism of toxicity formation during
      high-strength wastewater treatment. To investigate the relevant factors that
      contribute to sludge toxicity, synthetic wastewater with N,N-dimethylformamide
      (DMF) was treated in a sequential aerobic activated sludge reactor. The acute
      toxicity of sludge, which is characterised by the inhibition rate of luminous
      bacteria T3, is the focus of this study. Using an operational time of 28 days and
      a hydraulic retention time of 12h, the study demonstrated a positive relationship
      between the acute toxicity of sludge and the influent DMF concentration; the
      toxicity centralised in the intracellular and inner sections of extracellular
      polymeric substances (EPS) in sludge flocs. Due to increased concentrations of
      DMF, which ranged from 40 to 200mgL(-1), the sludge toxicity increased from 25 to
      45%. The organic toxicity in sludge flocs was primarily contributed by the
      biodegradation of DMF rather than adsorption of DMF. Additional investigation
      revealed a significant correlation between the properties of the bacterial
      community and sludge toxicity. 

PMID- 24316802
TI  - Ionic strength reduction and flow interruption enhanced colloid-facilitated Hg
      transport in contaminated soils.
AB  - The effects of ionic strength (IS) reduction (5-0.05mM) and flow interruption
      (FI, flow stopped for 7d) on colloid and Hg release in the leachate were examined
      in column experiment. Two Hg contaminated soils (13.9 and 146mg/kg) were used,
      with Hg concentrations in colloids being 2-4 times greater than bulk soils. Based
      on sequential extraction, Hg concentrations in organic matter (OM) fraction were
      the most abundant in soils (31-48%). Column leaching after IS reduction and FI
      released large amounts of colloidal Hg, accounting for 44-48% of released Hg. The
      highest colloidal Hg concentrations at 27.8 and 360MUg/L were observed at ~1 pore
      volume after FI. Concentration distribution of colloidal OM and colloidal Fe was
      similar to colloidal Hg in the leachate, showing peak concentrations after IS
      reduction and FI. Most of the released colloidal Hg was in OM fraction (37-53%),
      with some in Fe/Mn oxide fraction (11-19%). Based on composition of released
      colloids and Hg fractionation in soils and colloids, colloidal OM could serve as
      an important carrier for Hg transport in soils. 

PMID- 24316803
TI  - The effects of various control and water treatment processes on the membrane
      integrity and toxin fate of cyanobacteria.
AB  - Cyanobacterial blooms are one of the main contaminants that can degrade drinking
      water quality with the associated taste, odour and toxic compounds. Although a
      wide range of techniques have shown promise for cyanobacterial bloom control and
      cyanobacterial cell/metabolite removal in reservoirs and water treatment plants
      (WTPs), these treatments may have negative consequences through release of
      intracellular metabolites into the surrounding water. This study assessed the
      impact of copper sulphate (CuSO4), chlorine, potassium permanganate (KMnO4),
      hydrogen peroxide (H2O2) and ozone on Microcystis aeruginosa culture and the
      toxins it produced. All of these agents induced the loss of cyanobacterial
      membrane integrity. However, no associated increase in dissolved toxins was
      detected during chlorine and H2O2 treatments which may be due to faster toxin
      oxidation rates than release rates. KMnO4 doses of 1 and 3mgL(-1) degraded
      dissolved toxins while having no impact on cyanobacterial membrane integrity. In
      contrast, ozone induced a significant increase in extracellular toxins but it was
      unable to degrade these toxins to the same degree as the other oxidants which may
      due to the lack of residual. All chemicals, except CuSO4, were able to reduce
      cyanotoxins and chlorine was the most effective with a rate up to 2161M(-1)s(-1).

PMID- 24316804
TI  - Enhanced decomposition of dyes by hemin-ACF with significant improvement in pH
      tolerance and stability.
AB  - In this study, we evaluated a novel heterogeneous catalytic system (hemin
      ACF/H2O2) based on activated carbon fiber supported hemin for the rapid removal
      of dyes. Contrast experiments, effects of pH and temperature, and sustained
      catalytic stability of hemin-ACF for the catalytic decomposition of azo dye RR195
      used as a model pollutant were investigated. Surprisingly, the introduction of
      ACF significantly enhanced the decomposition of dyes by hemin with an obvious
      improvement in pH tolerance and stability. Inhibition and probe studies combined
      with electron paramagnetic resonance (EPR) were conducted to ascertain the role
      of several radicals (OH, O2(-)/HO2, (1)O2 and Fe(IV)O) on dye degradation. ACF
      are rich in free electrons, and the pi-conjugated macrocyclic structure of hemin
      may present convenient channels for the transfer of free electrons from the ACF,
      promoting the generation of hydroxyl radicals and high-valence iron species.
      These results are promising because they offer new insight for the application of
      hemin as a catalyzer upon treatment of organic pollutants and contribute to
      identification of the interaction between support material and catalyzer from a
      new perspective. 

PMID- 24316805
TI  - Adsorption of Ni(II) and Cd(II) from water by novel chelating sponge and the
      effect of alkali-earth metal ions on the adsorption.
AB  - Novel chelating sponge (PVA-M-H) was prepared with polyvinyl alcohol by graft
      polymerization and nucleophilic substitution. E.A, SEM, FT-IR, (13)CNMR, and XPS
      analyses were used to characterize PVA-M-H. The equilibrium adsorption capacities
      of PVA-M-H for Ni(II) and Cd(II) were 65.39 and 125.11mgg(-1), respectively.
      Within the range of 278-308K, the adsorption enthalpy changes of Ni(II) and
      Cd(II) on PVA-M-H were about 36.39-37.72kJmol(-1), and the free energy were about
      -13.27 to -1.7kJmol(-1). Both pseudo-first- and -second-order equations fit the
      adsorption kinetic curves well, and the initial adsorption rates of Ni(II) and
      Cd(II) onto PVA-M-H were 17.83 and 34.81mg (gmin)(-1), respectively. Although the
      presence of alkali-earth metal ions in solution decreased Ni(II) and Cd(II)
      removal, PVA-M-H still retained more than 60 and 80% of its adsorption capacity
      even as the concentration of Ca(2+) and Mg(2+) was up to 10mmolL(-1),
      respectively. Both 0.1M HCl and 0.1M EDTA solution could desorb Ni(II) and Cd(II)
      from PVA-M-H effectively, and the adsorption capacity of PVA-M-H for Ni(II) and
      Cd(II) could still maintain more than 90% level without any obvious decrease at
      the fifth cycle. 

PMID- 24316806
TI  - Removal of emerging contaminants by simultaneous application of membrane
      ultrafiltration, activated carbon adsorption, and ultrasound irradiation.
AB  - Advanced wastewater treatment is necessary to effectively remove emerging
      contaminants (ECs) with chronic toxicity, endocrine disrupting effects, and the
      capability to induce the proliferation of highly resistant microbial strains in
      the environment from before wastewater disposal or reuse. This paper investigates
      the efficiency of a novel hybrid process that applies membrane ultrafiltration,
      activated carbon adsorption, and ultrasound irradiation simultaneously to remove
      ECs. Diclofenac, carbamazepine, and amoxicillin are chosen for this investigation
      because of their assessed significant environmental risks. Removal mechanisms and
      enhancement effects are analysed in single and combined processes. The influence
      of adsorbent dose and ultrasonic frequency to EC removal are also investigated.
      Results suggest that adsorption is probably the main removal mechanism and is
      affected by the nature of ECs and the presence of other components in the
      mixture. Almost complete removals are achieved in the hybrid process for all ECs.

PMID- 24316807
TI  - An approach for estimating toxic releases of H2S-containing natural gas.
AB  - China is well known being rich in sulfurous natural gas with huge deposits widely
      distributed all over the country. Due to the toxic nature, the release of
      hydrogen sulfide-containing natural gas from the pipelines intends to impose
      serious threats to the human, society and environment around the release sources.
      CFD algorithm is adopted to simulate the dispersion process of gas, and the
      results prove that Gaussian plume model is suitable for determining the affected
      region of the well blowout of sulfide hydrogen-containing natural gas. In
      accordance with the analysis of release scenarios, the present study proposes a
      new approach for estimating the risk of hydrogen sulfide poisoning hazards, as
      caused by sulfide-hydrogen-containing natural gas releases. Historical accident
      statistical data from the EGIG (European Gas Pipeline Incident Data Group) and
      the Britain Gas Transco are integrated into the approach. Also, the dose-load
      effect is introduced to exploit the hazards' effects by two essential parameters 
      toxic concentration and exposure time. The approach was applied to three release
      scenarios occurring on the East-Sichuan Gas Transportation Project, and the
      individual risk and societal risk are classified and discussed. Results show that
      societal risk varies significantly with different factors, including population
      density, distance from pipeline, operating conditions and so on. Concerning the
      dispersion process of hazardous gas, available safe egress time was studied from
      the perspective of individual fatality risks. The present approach can provide
      reliable support for the safety management and maintenance of natural gas
      pipelines as well as evacuations that may occur after release incidents. 

PMID- 24316808
TI  - Air purification from TCE and PCE contamination in a hybrid bioreactors and
      biofilter integrated system.
AB  - A two-stage waste air treatment system, consisting of hybrid bioreactors
      (modified bioscrubbers) and a biofilter, was used to treat waste air containing
      chlorinated ethenes - trichloroethylene (TCE) and tetrachloroethylene (PCE). The
      bioreactor was operated with loadings in the range 0.46-5.50gm(-3)h(-1) for TCE
      and 2.16-9.02gm(-3)h(-1) for PCE. The biofilter loadings were in the range 0.1
      0.97gm(-3)h(-1) for TCE and 0.2-2.12gm(-3)h(-1) for PCE. Under low pollutant
      loadings, the efficiency of TCE elimination was 23-25% in the bioreactor and 54
      70% in the biofilter. The efficiency of PCE elimination was 44-60% in the
      bioreactor and 50-75% in the biofilter. The best results for the bioreactor were
      observed one week after the pollutant loading was increased. However, the process
      did not stabilize. In the next seven days contaminant removal efficiency,
      enzymatic activity and biomass content were all diminished. 

PMID- 24316809
TI  - Role of combinatorial environmental factors in the behavior and fate of ZnO
      nanoparticles in aqueous systems: a multiparametric analysis.
AB  - To better understand the environmental behavior, fate, and exposure risks of
      engineered nanoparticles in aquatic systems, for the first time, combinatorial
      aqueous systems were established using three-level orthogonal array design (OAD),
      an OA27 (3(1)(3)) matrix, to assess the effects of six co-varying environmental
      factors (organic acid type, organic acid concentration, NP concentration, pH,
      salt content, and electrolyte type) on the aggregation of commercial zinc oxide
      nanoparticles (ZnO NPs, mean diameter ~41nm). A separate set of OA27 (3(1)(3))
      experiments including temperature was conducted for the dissolution of these NPs.
      The results showed that the organic acid concentration and the pH were the most
      significant factors (p<0.001) influencing aggregation and dissolution of ZnO NPs,
      respectively. The electrolyte type and the salt content were the next most
      important factors in both the aggregation and dissolution. Based on the kinetics
      study of the aggregation, a high rate of the NP aggregation resulted in decreased
      dissolution, such that observed in the presence of calcium chloride. Clear
      temperature-induced aggregation and reduced dissolution were further observed
      with increasing temperature. This approach demonstrates that the behavior of ZnO
      NP may vary substantially under combinatorial environmental conditions. 

PMID- 24316810
TI  - Strontium adsorption on tantalum-doped hexagonal tungsten oxide.
AB  - Hexagonal tungsten oxide (hex-WO3) has the potential to separate (137)Cs and
      (90)Sr from nuclear power plant or fission (99)Mo production waste. This study
      aims to increase the capacity of hex-WO3 to adsorb Sr(2+). Ta-doped hex-WO3 was
      synthesized by the hydrothermal treatment of sodium tungstate dihydrate and
      tantalum chloride in concentrated HCl, in the presence of ammonium sulfate.
      Incorporating Ta into the WO3 framework caused the interlayer spacing to expand,
      and the band gap to shift to higher energy. The Sr(2+) adsorption capacity of Ta
      doped hex-WO3 was significantly higher than that of hex-WO3. Sr(2+) adsorption
      reached equilibrium within 2h in acidic solution. Maximum Sr(2+) removal occurred
      at pH 4. Sr(2+) uptake by hex-WO3 was described better by the Freundlich model
      than by the Langmuir model. Sr(2+) adsorption on hex-WO3 was spontaneous under
      the studied conditions. 

PMID- 24316811
TI  - Physicochemical and toxicological characteristics of particulate matter emitted
      from a non-road diesel engine: comparative evaluation of biodiesel-diesel and
      butanol-diesel blends.
AB  - Combustion experiments were conducted to evaluate the effects of using blends of
      ultralow sulfur diesel (ULSD) with biodiesel or n-butanol on physicochemical and
      toxicological characteristics of particulate emissions from a non-road diesel
      engine. The results indicated that compared to ULSD, both the blended fuels could
      effectively reduce the particulate mass and elemental carbon emissions, with
      butanol being more effective than biodiesel. The proportion of organic carbon and
      volatile organic compounds in particles increased for both blended fuels.
      However, biodiesel blended fuels showed lower total particle-phase polycyclic
      aromatic hydrocarbons (PAHs) emissions. The total number emissions of particles
      <=560nm in diameter decreased gradually for the butanol blended fuels, but
      increased significantly for the biodiesel blended fuels. Both the blended fuels
      indicated lower soot ignition temperature and activation energy. All the particle
      extracts showed a decline in cell viability with the increased dose. However, the
      change in cell viability among test fuels is not statistically significant
      different with the exception of DB-4 (biodiesel-diesel blend containing 4%
      oxygen) used at 75% engine load. 

PMID- 24316812
TI  - Environmental performance and mechanical analysis of concrete containing recycled
      asphalt pavement (RAP) and waste precast concrete as aggregate.
AB  - The overall objective of this research project was to investigate the feasibility
      of incorporating 100% recycled aggregates, either waste precast concrete or waste
      asphalt planning, as replacements for virgin aggregates in structural concrete
      and to determine the mechanical and environmental performance of concrete
      containing these aggregates. Four different types of concrete mixtures were
      designed with the same total water cement ratio (w/c=0.74) either by using
      natural aggregate as reference or by totally replacing the natural aggregate with
      recycled material. Ground granulated blast furnace slag (GGBS) was used as a
      mineral addition (35%) in all mixtures. The test results showed that it is
      possible to obtain satisfactory performance for strength characteristics of
      concrete containing recycled aggregates, if these aggregates are sourced from old
      precast concrete. However, from the perspective of the mechanical properties, the
      test results indicated that concrete with RAP aggregate cannot be used for
      structural applications. In terms of leaching, the results also showed that the
      environmental behaviour of the recycled aggregate concrete is similar to that of
      the natural aggregate concrete. 

PMID- 24316813
TI  - Changes in dissolved organic matter fluorescence and disinfection byproduct
      formation from UV and subsequent chlorination/chloramination.
AB  - Ultraviolet (UV) irradiation is being increasingly used to help drinking water
      utilities meet finished water quality regulations, but its influence on
      disinfection byproduct (DBP) precursors and DBP formation is not completely
      understood. This study investigated the effect of medium pressure (MP) UV
      combined with chlorination/chloramination on the fluorescent fraction of
      dissolved organic matter (DOM) isolated from a United States surface water with
      median total organic carbon content. Parallel factor analysis was used to
      understand how UV may alter the capacity of DOM to form DBPs of potential human
      health concern. The production of chloral hydrate and cyanogen chloride from MP
      UV followed by chlorine or chloramine, respectively, correlated with a decrease
      in fluorescence intensity of a protein/tryptophan-like component (R(2)=0.79-0.99)
      and a humic-like component (R(2)=0.91-1.00). This suggests that the UV-induced
      precursors to these compounds originated from DOM with similar characteristics to
      these components. The fluorescent DOM components identified in this study are
      similar to reoccurring components that have been previously identified in a range
      of raw and treated waters, and this work demonstrates the value of using
      fluorescence analysis of DOM to understand the relationships between DOM source
      and DBP formation under a range of treatment conditions. 

PMID- 24316814
TI  - Zinc oxide nanoparticles: genotoxicity, interactions with UV-light and cell
      transforming potential.
AB  - The in vitro genotoxic and the soft agar anchorage independent cell
      transformation ability of zinc oxide nanoparticles (NPs) and its bulky forms have
      been evaluated in human embryonic kidney (HEK293) and in mouse embryonic
      fibroblast (NIH/3T3) cells, either alone or in combination with UVB-light. The
      comet assay, with and without the use of FPG and Endo III enzymes, the
      micronucleus assay and the soft-agar colony assay were used. For the comet assay
      a statistically significant induction of DNA damage, with and without the
      enzymes, were observed up of 100MUg/mL. ZnO NPs were able to increase
      significantly the frequency of micronuclei, and similar results were observed in
      the cell transformation assay where such NPs were able to induce cell-anchorage
      independent growth. These effects were observed at doses up 100MUg/mL. Although
      UVB-light was able to induce genotoxic damage and cell-anchorage growth, a
      significant antagonist interaction effect was observed in combination with ZnO
      NPs. These in vitro results, obtained with the selected cell lines, contribute to
      increase our genotoxicity database on the ZnO NPs effects as well as to open the
      discussion about their risk in photo-protection sun screens. 

PMID- 24316815
TI  - The epidemiology and cost analysis of patients presented to Emergency Department
      following traffic accidents.
AB  - BACKGROUND: Traffic accidents are ranked first as the cause of personal injury
      throughout the world. The high number of traffic accidents yielding injuries and
      fatalities makes them of great importance to Emergency Departments. MATERIAL AND
      METHODS: Patients admitted to Hacettepe University Faculty of Medicine Adult
      Emergency Department due to traffic accidents were investigated
      epidemiologically. Differences between groups were evaluated by Kruskall-Wallis,
      Mann-Whitney, and Wilcoxon tests. A value of p<0.05 was accepted as statistically
      significant. RESULTS: We included 2003 patients over 16 years of age. The mean
      age was 39.6 +/- 16.1 and 55% were males. Admissions by ambulance and due to
      motor vehicle accidents were the most common. In 2004 the rate of traffic
      accidents (15.3%) was higher than the other years, the most common month was May
      (10.8%), and the most common time period was 6 pm to 12 am (midnight). About half
      of the patients (51.5%) were admitted in the first 30 minutes. Life-threatening
      condition was present in 9.6% of the patients. Head trauma was the most common
      type of trauma, with the rate of 18.3%. Mortality rate was 81.8%. The average
      length of hospital stay was 403 minutes (6.7 hours) and the average cost per
      patient was 983 +/- 4364 TL. CONCLUSIONS: Further studies are needed to compare
      the cost found in this study with the mean cost for Turkey. However, the most
      important step to reduce the direct and indirect costs due to traffic accidents
      is the prevention of these accidents.

PMID- 24316816
TI  - Selective catalytic burning of graphene by SiOx layer depletion.
AB  - We report catalytic decomposition of few-layer graphene on an Au/SiOx/Si surface
      wherein oxygen is supplied by dissociation of the native SiOx layer at a
      relatively low temperature of 400  degrees C. The detailed chemical evolution of
      the graphene covered SiOx/Si surface with and without gold during the catalytic
      process is investigated using a spatially resolved photoelectron emission method.
      The oxygen atoms from the native SiOx layer activate the gold-mediated catalytic
      decomposition of the entire graphene layer, resulting in the formation of direct
      contact between the Au and the Si substrate. The notably low contact resistivity
      found in this system suggests that the catalytic depletion of a SiOx layer could
      realize a new way to micromanufacture high-quality electrical contact. 

PMID- 24316817
TI  - Intermediate dipolar distances from spin labels.
AB  - Methods for determining inter-spin distances between nitroxide spin labels from
      dipolar couplings in the intermediate range (r12~1.1-2 nm) by CW-EPR are
      addressed. For nitroxide powder patterns, the assumption of unlike spins is a
      better approximation than assuming strong coupling between like spins. Methods
      that determine the average splitting in dipolar deconvolutions yield the mean
      value <1/r12(3)>, and those that determine the dipolar contribution to the
      spectral second moment correspondingly yield <1/r12(6)>. To relate these ensemble
      averages to the mean inter-spin distance <r12> requires knowledge of the
      distribution in r12. Values of the inverse roots reff,n=<1/r12(n)>(-1/n) always
      lie below <r12>. Consistent comparisons of literature data on double-labelled
      alpha-helical peptides support this view. Evaluations of reff,n for Gaussian
      distributions in r12 yield calibrations to determine <r12> for a given
      distribution width, sigma(r12).

PMID- 24316818
TI  - Fast REDOR with CPMG multiple-echo acquisition.
AB  - Rotational-Echo Double Resonance (REDOR) is a widely used experiment for distance
      measurements in solids. The conventional REDOR experiment measures the signal
      dephasing from hetero-nuclear recoupling under magic-angle spinning (MAS) in a
      point by point manner. A modified Carr-Purcell Meiboom-Gill (CPMG) multiple-echo
      scheme is introduced for fast REDOR measurement. REDOR curves are measured from
      the CPMG echo amplitude modulation under dipolar recoupling. The real time CPMG
      REDOR experiment can speed up the measurement by an order of magnitude. The
      effects from hetero-nuclear recoupling, the Bloch-Siegert shift and echo
      truncation to the signal acquisition are discussed and demonstrated. 

PMID- 24316819
TI  - Supramolecular high-aspect ratio assemblies with strong antifungal activity.
AB  - Efficient and pathogen-specific antifungal agents are required to mitigate drug
      resistance problems. Here we present cationic small molecules that exhibit
      excellent microbial selectivity with minimal host toxicity. Unlike typical
      cationic polymers possessing molecular weight distributions, these compounds have
      an absolute molecular weight aiding in isolation and characterization. However,
      their specific molecular recognition motif (terephthalamide-bisurea) facilitates
      spontaneous supramolecular self-assembly manifesting in several polymer-like
      properties. Computational modelling of the terephthalamide-bisurea structures
      predicts zig-zag or bent arrangements where distal benzyl urea groups stabilize
      the high-aspect ratio aqueous supramolecular assemblies. These nanostructures are
      confirmed by transmission electron microscopy and atomic force microscopy.
      Antifungal activity against drug-sensitive and drug-resistant strains with in
      vitro and in vivo biocompatibility is observed. Additionally, despite repeated
      sub-lethal exposures, drug resistance is not induced. Comparison with clinically
      used amphotericin B shows similar antifungal behaviour without any significant
      toxicity in a C. albicans biofilm-induced mouse keratitis model. 

PMID- 24316820
TI  - Big changes are ahead--a new format for crystallization communications in Acta
      Cryst. F.

PMID- 24316821
TI  - Coiled-coil dimerization of the LOV2 domain of the blue-light photoreceptor
      phototropin 1 from Arabidopsis thaliana.
AB  - A key role in signal transduction and dimerization mediated by Per-Arnt-Sim (PAS)
      domains is played by alpha-helical linkers that flank the structurally similar
      alpha/beta cores of these domains. However, crystal-packing forces and the
      different construct lengths and sequences of the PAS domains influence the final
      length and orientation of the linkers relative to the core and create uncertainty
      in the exact mechanism of the linker function. Thus, structural characterization
      and comparison of the linkers within isolated PAS-domain constructs and/or full
      length PAS-containing proteins is important for clarification of the mechanism.
      The plant blue-light photoreceptors phototropins possess two N-terminal flavin
      mononucleotide-based light, oxygen or voltage (LOV) domains (LOV1 and LOV2) that
      comprise a subclass of the PAS family and one C-terminal serine/threonine kinase
      domain whose enzymatic activity is regulated by blue light. The dark-adapted
      state crystal structures of the Arabidopsis thaliana phototropin 1 and
      phototropin 2 LOV1-domain constructs flanked by an N-terminal A'alpha helix and
      the structure of the phototropin 2 core LOV2 domain are known. Here, the crystal
      structure of the A. thaliana phototropin 1 LOV2 domain has been determined in its
      dark-adapted state. The core is flanked by an N-terminal A'alpha helix and a C
      terminal Jalpha helix similar to those in the previously reported structure of
      Avena sativa phototropin 1 LOV2. In contrast to the monomeric A. sativa LOV2, A.
      thaliana LOV2 is a dimer in which two A'alpha helices adopt a scissor-like
      orientation at the dimer interface and form a short alpha-helical coiled coil.
      The Jalpha helix predominantly interacts with the beta-sheet and plays a role in
      coiled-coil formation and dimerization. 

PMID- 24316822
TI  - Structure of the secretion domain of HxuA from Haemophilus influenzae.
AB  - Haemophilus influenzae HxuA is a cell-surface protein with haem-haemopexin
      binding activity which is key to haem acquisition from haemopexin and thus is one
      of the potential sources of haem for this microorganism. HxuA is secreted by its
      specific transporter HxuB. HxuA/HxuB belongs to the so-called two-partner
      secretion systems (TPSs) that are characterized by a conserved N-terminal domain
      in the secreted protein which is essential for secretion. Here, the 1.5 A
      resolution structure of the secretion domain of HxuA, HxuA301, is reported. The
      structure reveals that HxuA301 folds into a beta-helix domain with two extra
      helical motifs, a four-stranded beta-sheet and an N-terminal cap. Comparisons
      with other structures of TpsA secretion domains are reported. They reveal that
      despite limited sequence identity, strong structural similarities are found
      between the beta-helix motifs, consistent with the idea that the TPS domain plays
      a role not only in the interaction with the specific TpsB partners but also as
      the scaffold initiating progressive folding of the TpsA proteins at the bacterial
      surface. 

PMID- 24316823
TI  - Structure of the uracil complex of Vaccinia virus uracil DNA glycosylase.
AB  - Poxvirus uracil DNA glycosylases are the most diverse members of the family I
      uracil DNA glycosylases (UNGs). The crystal structure of the uracil complex of
      Vaccinia virus uracil DNA glycosylase (D4) was determined at 2.03 A resolution.
      One uracil molecule was located in the active-site pocket in each of the 12
      noncrystallographic symmetry-related D4 subunits. Although the UNGs of the
      poxviruses (including D4) feature significant differences in the characteristic
      motifs designated for uracil recognition and in the base-excision mechanism, the
      architecture of the active-site pocket in D4 is very similar to that in UNGs of
      other organisms. Overall, the interactions of the bound uracil with the active
      site residues are also similar to the interactions previously observed in the
      structures of human and Escherichia coli UNG.

PMID- 24316824
TI  - Structure of Acidothermus cellulolyticus family 74 glycoside hydrolase at 1.82 A
      resolution.
AB  - Here, a 1.82 A resolution X-ray structure of a glycoside hydrolase family 74
      (GH74) enzyme from Acidothermus cellulolyticus is reported. The resulting
      structure was refined to an R factor of 0.150 and an Rfree of 0.196. Structural
      analysis shows that five related structures have been reported with a secondary
      structure similarity of between 75 and 89%. The five similar structures were all
      either Clostridium thermocellum or Geotrichum sp. M128 GH74 xyloglucanases.
      Structural analysis indicates that the A. cellulolyticus GH74 enzyme is an
      endoxyloglucanase, as it lacks a characteristic loop that blocks one end of the
      active site in exoxyloglucanases. Superimposition with the C. thermocellum GH74
      shows that Asp451 and Asp38 are the catalytic residues. 

PMID- 24316825
TI  - Two high-resolution structures of the human E3 ubiquitin ligase Siah1.
AB  - Siah1 is an E3 ubiquitin ligase that contributes to proteasome-mediated
      degradation of multiple targets in key cellular processes and which shows promise
      as a therapeutic target in oncology. Structures of a truncated Siah1 bound to
      peptide-based inhibitors have been reported. Here, new crystallization conditions
      have allowed the determination of a construct encompassing dual zinc-finger
      subdomains and substrate-binding domains at significantly higher resolution.
      Although the crystals appear isomorphous, two structures present distinct states
      in which the spatial orientation of one zinc-finger subdomain differs with
      respect to the rest of the dimeric protein. Such a difference, which is
      indicative of conformational freedom, infers potential biological relevance
      related to recognition of binding partners. The crystallization conditions and
      improved models of Siah1 may aid future studies investigating Siah1-ligand
      complexes. 

PMID- 24316826
TI  - Structure of the beta-form of human MK2 in complex with the non-selective kinase
      inhibitor TEI-L03090.
AB  - Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2), a
      serine/threonine kinase from the p38 mitogen-activated protein kinase signalling
      pathway, plays an important role in the production of TNF-alpha and other
      cytokines. In a previous report, it was shown that MK2 in complex with the
      selective inhibitor TEI-I01800 adopts an alpha-helical glycine-rich loop that is
      induced by the stable nonplanar conformer of TEI-I01800. To understand the
      mechanism of the structural change, the structure of MK2 bound to TEI-L03090,
      which lacks the key substituent found in TEI-I01800, was determined. MK2-TEI
      L03090 has a beta-sheet glycine-rich loop in common with other kinases, as
      predicted. This result suggests that a small compound can induce a drastic
      conformational change in the target protein structure and can be used to design
      potent and selective inhibitors. 

PMID- 24316827
TI  - Crystallization and preliminary X-ray crystallographic analysis of the curli
      transporter CsgG.
AB  - Gram-negative bacteria have eight known protein secretion systems. The type-VIII
      secretion system, also known as the curli biosynthesis system, is responsible for
      the formation of aggregative fibres known in Escherichia coli as curli. Curli are
      extracellular proteinaceous fibres primarily involved in bacterial biofilm
      formation and attachment to nonbiotic surfaces. The secretion of curli subunits
      depends on a dedicated lipoprotein, CsgG, which is found to form an oligomeric
      secretion channel in the outer membrane. A nonlipidated mutant of CsgG was
      expressed and crystallized in a soluble form. The crystals diffracted to 3.15 A
      resolution and belong to space group P1 with a unit cell containing a predicted
      16 molecules per asymmetric unit.

PMID- 24316828
TI  - Purification, crystallization and preliminary X-ray studies of MbtN (Rv1346) from
      Mycobacterium tuberculosis.
AB  - In Mycobacterium tuberculosis, the protein MbtN (Rv1346) catalyzes the formation
      of a double bond in the fatty-acyl moiety of the siderophore mycobactin, which is
      used by this organism to acquire essential iron. MbtN is homologous to acyl-CoA
      dehydrogenases, whose general role is to catalyze the alpha,beta-dehydrogenation
      of fatty-acyl-CoA conjugates. Mycobactins, however, contain a long unsaturated
      fatty-acid chain with an unusual cis double bond conjugated to the carbonyl group
      of the mycobactin core. To characterize the role of MbtN in the dehydrogenation
      of this fatty-acyl moiety, the enzyme has been expressed, purified and
      crystallized. The crystals diffracted to 2.3 A resolution at a synchrotron source
      and were found to belong to the hexagonal space group H32, with unit-cell
      parameters a = b = 139.10, c = 253.09 A, alpha = beta = 90, gamma = 120 degrees .

PMID- 24316829
TI  - Crystallization and preliminary X-ray crystallographic analysis of human
      peptidylarginine deiminase type I.
AB  - Peptidylarginine deiminase (PAD) catalyzes the post-translational conversion of
      peptidylarginine to peptidylcitrulline in the presence of calcium ions. Among the
      five known human PAD isozymes (PAD1-4 and PAD6), PAD1 exhibits the broadest
      substrate specificity. Crystals of PAD1 obtained using polyethylene glycol 3350
      as a precipitant diffracted to 3.70 A resolution using synchrotron radiation. Two
      PAD1 molecules were contained in the asymmetric unit and the crystals belonged to
      space group P6(1), with unit-cell parameters a = b = 90.3, c = 372.3 A. The
      solvent content was 58.2%.

PMID- 24316830
TI  - Crystallization and preliminary X-ray diffraction analysis of an active-site
      mutant of 'loopless' family GH19 chitinase from Bryum coronatum in a complex with
      chitotetraose.
AB  - The catalytic mechanism of family GH19 chitinases is not well understood owing to
      insufficient information regarding the three-dimensional structures of enzyme
      substrate complexes. Here, the crystallization and preliminary X-ray diffraction
      analysis of a selenomethionine-labelled active-site mutant of 'loopless' family
      GH19 chitinase from the moss Bryum coronatum in complex with chitotetraose,
      (GlcNAc)4, are reported. The crystals were grown using the vapour-diffusion
      method. They diffracted to 1.58 A resolution using synchrotron radiation at the
      Photon Factory. The crystals belonged to the monoclinic space group C2, with unit
      cell parameters a = 74.5, b = 58.4, c = 48.1 A, beta = 115.6 degrees . The
      asymmetric unit of the crystals is expected to contain one protein molecule, with
      a Matthews coefficient of 2.08 A(3) Da(-1) and a solvent content of 41%.

PMID- 24316831
TI  - Crystallization of the C-terminal domain of the bacteriophage T5 L-shaped fibre.
AB  - Tails of bacteriophage T5 (a member of the Siphoviridae family) were studied by
      electron microscopy. For the distal parts of the L-shaped tail fibres, which are
      involved in host cell receptor binding, a low-resolution volume was calculated.
      Several C-terminal fragments of the fibre were expressed and purified. Crystals
      of two of them were obtained that belonged to space groups P63 and R32 and
      diffracted synchrotron radiation to 2.3 and 2.9 A resolution, respectively. A
      single-wavelength anomalous dispersion data set to 2.5 A resolution was also
      collected from a selenomethionine-derivatized crystal of one of the fragments,
      which belonged to space group C2.

PMID- 24316832
TI  - Two-dimensional crystallization of intact F-ATP synthase isolated from bovine
      heart mitochondria.
AB  - Mitochondrial F-ATP synthase produces the majority of ATP for cellular functions
      requiring free energy. The structural basis for proton motive force-driven
      rotational catalysis of ATP formation in the holoenzyme remains to be determined.
      Here, the purification and two-dimensional crystallization of bovine heart
      mitochondrial F-ATP synthase are reported. Two-dimensional crystals of up to 1 um
      in size were grown by dialysis-mediated detergent removal from a mixture of
      decylmaltoside-solubilized 1,2-dimyristoyl-sn-glycero-3-phosphocholine and F-ATP
      synthase against a detergent-free buffer. A projection map calculated from an
      electron micrograph of a negatively stained two-dimensional crystal revealed unit
      cell parameters of a = 185.0, b = 170.3 A, gamma = 92.5 degrees .

PMID- 24316833
TI  - Crystallization and preliminary crystallographic analysis of the chimeric protein
      LKB1-14-3-3zeta.
AB  - LKB1, a tumour suppressor, plays key roles in cell polarity, cell growth and
      energy metabolism. 14-3-3 proteins bind to LKB1 and suppress its functions. A
      chimera containing 14-3-3zeta and its binding region in LKB1 was constructed and
      the chimeric protein LKB1-14-4-3zeta was purified and crystallized. The crystal
      of LKB1-14-4-3zeta diffracted to 2.9 A resolution and belonged to space group
      R32, with unit-cell parameters a = b = 130.262, c = 264.960 A. Structure
      determination and refinement are in progress.

PMID- 24316834
TI  - Crystallization of the C-terminal domain of the fibre protein from snake
      adenovirus 1, an atadenovirus.
AB  - Adenovirus fibre proteins play an important role in determining viral tropism.
      The C-terminal domain of the fibre protein from snake adenovirus type 1, a member
      of the Atadenovirus genus, has been expressed, purified and crystallized.
      Crystals were obtained belonging to space groups P2(1)2(1)2(1) (two different
      forms), I2(1)3 and F23. The best of these diffracted synchrotron radiation to a
      resolution of 1.4 A. As the protein lacks methionines or cysteines, site-directed
      mutagenesis was performed to change two leucine residues to methionines. Crystals
      of selenomethionine-derivatized crystals of the I2(1)3 form were also obtained
      and a multi-wavelength anomalous dispersion data set was collected.

PMID- 24316835
TI  - Crystallization and preliminary crystallographic analysis of a surface antigen
      glycoprotein, SAG19, from Eimeria tenella.
AB  - Coccidiosis in chickens is caused by the apicomplexan parasite Eimeria tenella
      and is thought to involve a role for a superfamily of more than 20 cysteine-rich
      surface antigen glycoproteins (SAGs) in host-parasite interactions. A
      representative member of the family, SAG19, has been overexpressed in Escherichia
      coli, purified and crystallized by the hanging-drop method of vapour diffusion
      using ammonium sulfate as the precipitant. Crystals of SAG19 diffracted to beyond
      1.50 A resolution and belonged to space group I4, with unit-cell parameters a = b
      = 108.2, c = 37.5 A. Calculation of possible values of VM suggests that there is
      a single molecule in the asymmetric unit.

PMID- 24316836
TI  - Crystallization and preliminary X-ray analysis of the ATPase domain of the
      sigma(54)-dependent transcription activator NtrC1 from Aquifex aeolicus bound to
      the ATP analog ADP-BeFx.
AB  - One way that bacteria regulate the transcription of specific genes to adapt to
      environmental challenges is to use different sigma factors that direct the RNA
      polymerase holoenzyme to distinct promoters. Unlike sigma(70) RNA polymerase
      (RNAP), sigma(54) RNAP is unable to initiate transcription without an activator:
      enhancer-binding protein (EBP). All EBPs contain one ATPase domain that belongs
      to the family of ATPases associated with various cellular activities (AAA+
      ATPases). AAA+ ATPases use the energy of ATP hydrolysis to remodel different
      target macromolecules to perform distinct functions. These mechanochemical
      enzymes are known to form ring-shaped oligomers whose conformations strongly
      depend upon nucleotide status. Here, the crystallization of the AAA+ ATPase
      domain of an EBP from Aquifex aeolicus, NtrC1, in the presence of the non
      hydrolyzable ATP analog ADP-BeFx is reported. X-ray diffraction data were
      collected from two crystals from two different protein fractions of the NtrC1
      ATPase domain. Previously, this domain was co-crystallized with ADP and ATP, but
      the latter crystals were grown from the Walker B substitution variant E239A.
      Therefore, the new data sets are the first for a wild-type EBP ATPase domain co
      crystallized with an ATP analog and they reveal a new crystal form. The resulting
      structure(s) will shed light on the mechanism of EBP-type transcription
      activators. 

PMID- 24316837
TI  - Crystallization and sulfur SAD phasing of AggA, the major subunit of aggregative
      adherence fimbriae type I from the Escherichia coli strain that caused an
      outbreak of haemolytic-uraemic syndrome in Germany.
AB  - The outbreak of Shiga toxin-producing Escherichia coli O104:H4 infection in
      Germany in 2011 was associated with significant mortality and morbidity owing to
      the progressive development of haemolytic-uraemic syndrome. The outbreak strain
      emerged recently as a result of horizontal transfer events leading to the
      acquisition of a number of virulence factors. Among them, aggregative adherence
      fimbriae type I (AAF/I) are considered to be particularly important since they
      are involved in the initial attachment of bacteria to the intestinal mucosa.
      Here, the crystallization and preliminary X-ray diffraction analysis of the major
      subunit of AAF/I, AggA, are reported. Crystallization of recombinant donor-strand
      complemented AggA was performed by the vapour-diffusion method. The crystals
      diffracted to 1.55 A resolution and belonged to the orthorhombic space group
      C222(1), with unit-cell parameters a = 77.83, b = 80.17, c = 91.42 A. Despite a
      low sulfur content of the protein [0.57%(w/w)], sufficiently accurate initial
      phases were derived from a sulfur SAD experiment.

PMID- 24316838
TI  - Crystallization of the CHAP domain of the endolysin from Staphylococcus aureus
      bacteriophage K.
AB  - CHAP(K) is the N-terminal cysteine, histidine-dependent amidohydrolase/peptidase
      domain (CHAP domain) of the Staphylococcus aureus bacteriophage K endolysin LysK.
      It is formed from the first 165 residues of LysK and functions by cleaving
      specific peptidoglycan peptide bonds, causing bacterial lysis. CHAP(K) can lyse
      S. aureus when applied exogenously, making it a good candidate for the treatment
      of multidrug-resistant Staphylococcus aureus infections. Here, the
      crystallization of CHAP(K) and the collection of native and derivative data to
      high resolution, which allowed structure solution, are reported. The structure
      may help to elucidate the mechanism of action and in the design of chimeric
      proteins or mutants with improved antibacterial activity.

PMID- 24316839
TI  - Purification, crystallization and preliminary X-ray analysis of IMP-18, a class B
      carbapenemase from Pseudomonas aeruginosa.
AB  - Class B beta-lactamases are known as metallo-beta-lactamases (MBLs) and they
      hydrolyze most beta-lactams, including carbapenems. IMP-18, an MBL cloned from
      Pseudomonas aeruginosa, was overexpressed, purified and crystallized by vapour
      diffusion for X-ray crystallographic analysis. Preliminary X-ray analysis showed
      that the crystal diffracted to 2.4 A resolution and belonged to the tetragonal
      space group P4(1)2(1)2, with unit-cell parameters a = b = 120.77, c = 96.54 A,
      alpha = beta = gamma = 90 degrees , suggesting the presence of two molecules in
      the asymmetric unit.

PMID- 24316840
TI  - Preliminary crystallographic studies of BRCA1 BRCT-ABRAXAS complex.
AB  - The BRCA1 holoenzyme complex plays an important role in DNA damage repair.
      ABRAXAS is a newly discovered component of this complex and its C-terminal region
      directly binds to the BRCA1 BRCT domain. Single crystals of the BRCA1 BRCT
      ABRAXAS complex grown by co-crystallization belonged to space group P4(1)2(1)2,
      with unit-cell parameters a = b = 187.18, c = 85.31 A. Diffraction data were
      collected on the BM-14 beamline at the ESRF. Molecular-replacement calculations
      using Phaser led to three molecules in the asymmetric unit and a high solvent
      content of 76%.

PMID- 24316841
TI  - Liquid-liquid diffusion crystallization improves the X-ray diffraction of EndoS,
      an endo-beta-N-acetylglucosaminidase from Streptococcus pyogenes with activity on
      human IgG.
AB  - Endoglycosidase S (EndoS) is an enzyme secreted by Streptococcus pyogenes that
      specifically hydrolyzes the beta-1,4-di-N-acetylchitobiose core glycan on
      immunoglobulin G (IgG) antibodies. One of the most common human pathogens and the
      cause of group A streptococcal infections, S. pyogenes secretes EndoS in order to
      evade the host immune system by rendering IgG effector mechanisms dysfunctional.
      On account of its specificity for IgG, EndoS has also been used extensively for
      chemoenzymatic synthesis of homogeneous IgG glycoprotein preparations and is
      being developed as a novel therapeutic for a wide range of autoimmune diseases.
      The structural basis of its enzymatic activity and substrate specificity,
      however, remains unknown. Here, the purification and crystallization of EndoS are
      reported. Using traditional hanging-drop and sitting-drop vapor-diffusion
      crystallization, crystals of EndoS were grown that diffracted to a maximum of 3.5
      A resolution but suffered from severe anisotropy, the data from which could only
      be reasonably processed to 7.5 A resolution. When EndoS was crystallized by
      liquid-liquid diffusion, it was possible to grow crystals with a different space
      group to those obtained by vapor diffusion. Crystals of wild-type endoglycosidase
      and glycosynthase constructs of EndoS grown by liquid-liquid diffusion diffracted
      to 2.6 and 1.9 A resolution, respectively, with a greatly diminished anisotropy.
      Despite extensive efforts, the failure to reproduce these liquid-liquid diffusion
      grown crystals by vapor diffusion suggests that these crystallization methods
      each sample a distinct crystallization space.

PMID- 24316842
TI  - Crystallization and preliminary X-ray crystallographic analysis of the inhibitory
      domain of the tomato mosaic virus resistance protein Tm-1.
AB  - Tm-1, an inhibitor protein of Tomato mosaic virus RNA replication, contains two
      conserved domains: an uncharacterized domain at its N-terminus and a TIM-barrel
      like domain at its C-terminus. The N-terminal domain of Tm-1 has an inhibitory
      activity and its three-dimensional structure has not been determined. Here, the
      crystallization and preliminary X-ray diffraction of the N-terminal domain of Tm
      1 are reported. A three-wavelength MAD data set was collected from a
      selenomethionine-labelled crystal and processed to 2.7 A resolution. The crystal
      belonged to the triclinic space group P1, with unit-cell parameters a = 77.97, b
      = 105.28, c = 110.62 A, alpha = 94.6, beta = 109.3, gamma = 108.0 degrees .

PMID- 24316843
TI  - Crystallization and preliminary X-ray diffraction studies of the (R)-selective
      amine transaminase from Aspergillus fumigatus.
AB  - The (R)-selective amine transaminase from Aspergillus fumigatus was expressed in
      Escherichia coli and purified to homogeneity. Bright yellow crystals appeared
      while storing the concentrated solution in the refrigerator and belonged to space
      group C222(1). X-ray diffraction data were collected to 1.27 A resolution, as
      well as an anomalous data set to 1.84 A resolution that was suitable for S-SAD
      phasing.

PMID- 24316844
TI  - Expression, purification, crystallization and preliminary X-ray analysis of the
      receiver domain of Staphylococcus aureus LytR protein.
AB  - The response-regulatory protein LytR belongs to a family of transcription factors
      involved in the regulation of important virulence factors in pathogenic bacteria.
      The protein consists of a receiver domain and an effector domain, which play an
      important role in controlled cell death and lysis. The LytR receiver domain
      (LytR(N)) has been overexpressed, purified and crystallized using the sitting
      drop and hanging-drop vapour-diffusion methods. The crystals grew as needles,
      with unit-cell parameters a = b = 84.82, c = 157.3 A, alpha = beta = 90, gamma =
      120 degrees . LytR(N) crystallized in space group P6122 and the crystals
      diffracted to a maximum resolution of 2.34 A. Based on the Matthews coefficient
      (V(M) = 5.44 A(3) Da(-1)), one molecule is estimated to be present in the
      asymmetric unit.

PMID- 24316845
TI  - Cloning, expression, purification, crystallization and preliminary X-ray studies
      of argininosuccinate lyase (Rv1659) from Mycobacterium tuberculosis.
AB  - The last enzyme in the arginine-biosynthesis pathway, argininosuccinate lyase,
      from Mycobacterium tuberculosis has been cloned, expressed, purified and
      crystallized, and preliminary X-ray studies have been carried out on the
      crystals. The His-tagged tetrameric enzyme with a subunit molecular weight of
      50.9 kDa crystallized with two tetramers in the asymmetric unit of the
      orthorhombic unit cell, space group P2(1)2(1)2(1). Molecular-replacement
      calculations and self-rotation calculations confirmed the space group and the
      tetrameric nature of the molecule.

PMID- 24316846
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      analysis of the aspartate transcarbamoylase domain of human CAD.
AB  - Aspartate transcarbamoylase (ATCase) catalyzes the synthesis of N-carbamoyl-L
      aspartate from carbamoyl phosphate and aspartate in the second step of the de
      novo biosynthesis of pyrimidines. In prokaryotes, the first three activities of
      the pathway, namely carbamoyl phosphate synthetase (CPSase), ATCase and
      dihydroorotase (DHOase), are encoded as distinct proteins that function
      independently or in noncovalent association. In animals, CPSase, ATCase and
      DHOase are part of a 243 kDa multifunctional polypeptide named CAD. Up-regulation
      of CAD is essential for normal and tumour cell proliferation. Although the
      structures of numerous prokaryotic ATCases have been determined, there is no
      structural information about any eukaryotic ATCase. In fact, the only detailed
      structural information about CAD is that it self-assembles into hexamers and
      trimers through interactions of the ATCase domains. Here, the expression,
      purification and crystallization of the ATCase domain of human CAD is reported.
      The recombinant protein, which was expressed in bacteria and purified with good
      yield, formed homotrimers in solution. Crystallization experiments both in the
      absence and in the presence of the inhibitor PALA yielded small crystals that
      diffracted X-rays to 2.1 A resolution using synchrotron radiation. The crystals
      appeared to belong to the hexagonal space group P6(3)22, and Matthews coefficient
      calculation indicated the presence of one ATCase subunit per asymmetric unit,
      with a solvent content of 48%. However, analysis of the intensity statistics
      suggests a special case of the P21 lattice with pseudo-symmetry and possibly
      twinning.

PMID- 24316847
TI  - Purification, crystallization and preliminary crystallographic analysis of the
      ligand-binding regions of the PctA and PctB chemoreceptors from Pseudomonas
      aeruginosa in complex with amino acids.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen and one of the major model
      organisms for the study of chemotaxis. The bacterium harbours 26 genes encoding
      chemoreceptors, most of which have not been annotated with a function. The
      paralogous chemoreceptors PctA and PctB (Pseudomonas chemotactic transducer A and
      B) were found to mediate chemotaxis towards L-amino acids. However, the ligand
      spectrum of the receptors is quite different since the recombinant ligand-binding
      region (LBR) of PctA binds 17 different L-amino acids whereas that of PctB
      recognizes only five. To determine the molecular basis underlying this ligand
      specificity, PctA-LBR and PctB-LBR have been purified and crystals have been
      produced after pre-incubation with L-Ile and L-Arg, respectively. Initial
      crystallization conditions have been identified by the counter-diffusion method
      and X-ray data have been collected at 2.5 A (PctA-LBR bound to L-Ile) and 3.14 A
      (PctB-LBR bound to L-Arg) resolution. Crystals belonged to space groups
      P2(1)2(1)2(1) and P3(1)2(1), with unit-cell parameters a = 72.2, b = 78.5, c =
      116.6 A and a = b = 111.6, c = 117.4, respectively, for PctA-LBR and PctB-LBR.
      Molecular-replacement methods will be pursued for structural determination.

PMID- 24316848
TI  - Crystallization and preliminary X-ray diffraction analysis of D53H mutant
      Escherichia coli cAMP receptor protein.
AB  - The Escherichia coli cyclic AMP receptor protein (CRP) is a prokaryotic global
      transcription activator protein that controls the expression of many different
      genes. Wild-type CRP can bind to special DNA sequences in the presence of cAMP.
      The substitution of Asp53 by His results in the CRP* phenotype, which does not
      require exogenous cAMP. In the present study, the D53H CRP mutant was
      overexpressed, purified and crystallized. cAMP-free D53H CRP crystals were
      obtained and diffracted to a resolution of 2.9 A. Based on the systematic
      absences of the crystals, the space group is likely to be P2(1)2(1)2(1), with
      unit-cell parameters a = 76.66, b = 152.14, c = 176.11 A. The asymmetric unit was
      confirmed to contain four protein dimers, with a Matthews coefficient of 2.71
      A(3) Da(-1) and a solvent content of 54.68%.

PMID- 24316850
TI  - Enantioselective synthesis of diaryl aziridines using tetrahydrothiophene-based
      chiral sulfides as organocatalysts.
AB  - This work describes catalytic and asymmetric aziridinations (15 examples, 95-98%
      ee) of benzyl bromide and imines via the imino Corey-Chaykovsky reaction using
      (thiolan-2-yl)diarylmethanol benzyl ether as an organocatalyst. The catalyst and
      analogues thereof were prepared through an expeditious and efficient synthetic
      route featuring a double nucleophilic substitution and Shi epoxidation as key
      steps. 

PMID- 24316849
TI  - Overexpression, crystallization and preliminary X-ray crystallographic analysis
      of glucuronoxylan xylanohydrolase (Xyn30A) from Clostridium thermocellum.
AB  - The modular carbohydrate-active enzyme belonging to glycoside hydrolase family 30
      (GH30) from Clostridium thermocellum (CtXynGH30) is a cellulosomal protein which
      plays an important role in plant cell-wall degradation. The full-length CtXynGH30
      contains an N-terminal catalytic module (Xyn30A) followed by a family 6
      carbohydrate-binding module (CBM6) and a dockerin at the C-terminus. The
      recombinant protein has a molecular mass of 45 kDa. Preliminary structural
      characterization was carried out on Xyn30A crystallized in different conditions.
      All tested crystals belonged to space group P1 with one molecule in the
      asymmetric unit. Molecular replacement has been used to solve the Xyn30A
      structure.

PMID- 24316851
TI  - The provision of home-based palliative care for those with advanced heart
      failure.
AB  - PURPOSE OF REVIEW: Although widely recognized as best practice for advanced heart
      failure patients, palliative care is underused by this population. The purpose of
      this brief review is to highlight recent findings related to home-based
      palliative care among patients with advanced heart failure. RECENT FINDINGS: This
      review considers new models of home-based palliative care and reports recent
      evidence on the effectiveness, and burden of these models for patients with
      advanced heart failure and their caregivers. New models currently under
      investigation and gaps in current research are presented. SUMMARY: New models
      integrating home-based palliative care and standard heart failure care have shown
      to be effective in reducing both physical and psychological symptoms in patients.
      Recent evidence suggests that home-based palliative care reduces hospitalizations
      and decrease the probability of 30-day re-admissions in patients with advanced
      heart failure; thus, potentially reducing costs of care and increasing likelihood
      of dying at home. However, caregiver burden for families of those with heart
      failure remains an issue. Research that addresses caregiver burden and the
      challenges of providing palliative care to patients with the uncertain disease
      trajectory seen in advanced heart failure require further research.

PMID- 24316852
TI  - Adhesion prevention in reabsorbable polyethylene glycol hydrogel (Coseal(r))
      coated polypropylene mesh in rabbits.
AB  - PURPOSE: To evaluate of postoperative adhesion prevention and inflammatory
      response to polypropylene mesh, coated with reabsorbable hydrogel of polyethylene
      glycol (Coseal(r)) in contact with small bowel in an experimental model in
      rabbits. METHODS: Twenty female rabbits underwent laparotomy to implant two
      polypropylene meshes, 2 x 1 cm, in the right and left flanks. The right mesh was
      protected with Coseal(r) spray (Group 1) and the left mesh received no treatment
      after implantation (Group 2). Thirty days after implantation, the rabbits
      underwent laparoscopy for adhesion analysis; the prosthesis were removed en bloc
      with the adjacent tissue for microscopic analysis of inflammation. Statistical
      analysis used the Mann-Whitney test. RESULTS: There was adhesion formation in
      five meshes (36%) from Group 1 and in 14 meshes (100%) from Group 2, with
      statistical significance (p<0.01). There were no differences in the inflammatory
      response, fibrosis, foreign body reaction, presence of collagen and type of
      inflammatory cells between the two groups. CONCLUSION: Polypropylene mesh coated
      with Coseal(r) showed a significantly lower rate of adhesion formation when
      compared with uncoated meshes, without interfering with inflammatory response.

PMID- 24316853
TI  - New experimental model of exposure to environmental tobacco smoke.
AB  - PURPOSE: To describe a new model to passive smoking for rodents. METHODS: Twenty
      rats were distributed into two study groups (N=10): control group (CG), that was
      not exposed to tobacco smoke and used as normal standard for biochemical and
      histological analysis; Experimental Group (EG), that Animals were exposed to the
      passive smoking; Euthanasia was performed after 14 days of exposure. The serum
      level of nicotine and histological analysis were performed. RESULTS: There was a
      statistical difference on the nicotine serum levels between Experimental and
      Control group, with level of 286 +/- 23 nanograma/mL in the EG and undetectable
      on CG (p<0.01). The histological study suggested the model efficacy producing
      alveolar destruction and emphysema in the EG compared with the insignificant
      lesions in the CG's lung. CONCLUSION: The model of exposure to environmental
      tobacco smoke for rodents induced easily the changes related to secondhand smoke.

PMID- 24316854
TI  - Neovascularization after surgical exposure of rat external jugular vein
      endothelium.
AB  - PURPOSE: To investigate the neovascularization after exposure of the external
      jugular venous endothelium in an experimental model. METHODS: The sample was
      composed of 60 male rats of Wistar OUT B breed provided by animal colony of the
      Medicine College of Juazeiro do Norte, weighing 250 to 350 g, aged 90-120 days.
      Randomized study in OUT B Wistar rats, open, with 60 days duration. The animals
      were distributed into three groups of 20 specimens and were subjected to the
      following: Group 1: neck incision with dissection, ligation and section of the
      external jugular vein. Group 2: neck incision with dissection and ligation of the
      external jugular vein. Group 3: cervicotomy without dissection of the external
      jugular vein without ligation or section. The animals were sacrificed, half of
      them in 30 days and the other half within 60 days. The material in block
      harvested from the operated site were sectioned and stained for
      immunohistochemistry with CD34 marker. RESULTS: Neovascularization occurred with
      level of significance when compared group 1 to group 3 at 30 days (p=0.0076) and
      the same occurred at 60 days (p=0.0001) (Newman-Keuls test). CONCLUSION: The
      group with exposure of the venous endothelium showed a significant increase of
      neovascularization when compared with other groups.

PMID- 24316855
TI  - An outcome analysis and long-term viability of cryopreserved cultured epidermal
      allografts: assessment of the conservation of transplantable human skin
      allografts.
AB  - PURPOSE: To assess the viability of cultured epithelium and preserved by freezing
      for periods varying from one month to one year. METHODS: Samples of cultured
      epithelium were incubated in cryoprotectant medium (Group A), packed in aluminum
      envelopes and packed in polystyrene boxes. The boxes were subjected to a
      temperature of-70 oC. After freezing for a period of time ranging from one to 12
      months, cultured epithelial samples were assessed for their viability by vital
      staining (Trypan blue) and metabolic analysis based on glucose consumption and
      lactate production. Samples of not frozen cultured epithelium (Group B) were also
      tested for viability and the results obtained were used as comparison parameter
      for the variation of viability. RESULTS: Statistical analysis between the group A
      and B indicate that the mean age of the donors (p=0.51) and the culture time
      (p=1.18) showed no statistical difference. In 30 days we obtained 37% of the
      original viability of cultured epithelium, 25% at six months and one year, less
      than 15%. This trend was confirmed statistically with a reduction of
      approximately 1.8% of the original viability epithelium cultured every 30 days of
      storage. In the analysis by lactate production, similar results were observed. In
      the analysis by the glucose consumption results were not significant. The
      viability indices show statistically significant difference between the group A
      and B (p<0.0001). CONCLUSIONS: Although cryopreserved cultured epithelium showed
      significant reduction of viability, all samples remained viable. It was also
      found that the viability of cryopreserved cultured epithelial decreased as a
      function of storage time.

PMID- 24316856
TI  - Effects of propofol in lipid-based emulsion and in microemulsion on the incidence
      of endothelial lesion in rabbits.
AB  - PURPOSE: To compare the incidence of endothelial injury after single-dose or
      continuous propofol infusion in conventional lipid-based emulsion (LE) versus
      microemulsion (ME). METHODS: Forty-two rabbits (2.5-4.5 Kg) were randomly
      allocated into seven groups of six animals each: SHAM- surgical treatment alone;
      Bolus Control Group - 3 mL-intravenous (IV) bolus of saline; Continuous Infusion
      Control Group - 3 mL- IV bolus of saline followed by a continuous infusion of 0.2
      ml/kg/min for 60 min; Bolus LE Propofol Group - IV bolus of LE propofol (3
      mg/kg); Bolus ME Propofol Group - IV ME propofol bolus (3 mg/kg); Continuous LE
      Propofol Group - IV LE propofol bolus (3 mg/kg) followed by a continuous infusion
      of 0.2 ml/kg/min for 60 min; Continuous ME Propofol Group - IV ME propofol bolus
      (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min. RESULTS:
      There were no statistically significant differences between the studied groups in
      blood pressure, in central venous pressure and in the biochemical profile. No
      significant differences were found in inflammatory mediators and in tissue
      analysis between the two emulsions. CONCLUSION: Microemulsion and lipid-based
      emulsion propofol had similar inflammatory, biochemical and microscopy profiles.
      Thus, microemulsion propofol can be used as an alternative to lipid-based
      emulsion propofol.

PMID- 24316857
TI  - Nonsteroidal anti-inflammatory therapy: changes on renal function of healthy
      dogs.
AB  - PURPOSE: To evaluate the renal function in healthy dogs submitted to nonselective
      and preferential COX-2 nonsteroidal anti-inflammatory drug (NSAID) therapy.
      METHODS: Twenty four healthy dogs were distributed into four groups (G) (n=6):
      ketoprofenG--treated with ketoprofen; nimesulideG--treated with nimesulid;
      meloxicanG--treated with meloxican; and etodolacG--treated with etodolaco. All
      the dogs received the NSAIDs for 10 days by oral route. Physical examination and
      renal function (urinalysis, urinary sodium and gamma-glutamyl transpeptidase
      (GGT), serum urea, creatinine, potassium and sodium, and endogenous creatinine
      clearance) were evaluated before, after five and ten days (T0, T5 and T10) of the
      treatment in all groups. RESULTS: Changes were observed in urinalysis, with a
      significant increase in renal cells in the urine at T5 and T10 in nimesulideG.
      Significant reduction in urinary sodium in nimesulideG at T5 was observed. The
      clearance values were lower in ketoprofenG at T10. CONCLUSIONS: Meloxicam and
      etodolac were the drugs that have proven to be safer for short-term therapy in
      healthy dogs in relation to renal function. NSAIDs ketoprofen and nimesulide
      should be used judiciously in dogs with renal dysfunction, since there are
      promoted changes in renal function.

PMID- 24316858
TI  - Expression of oxidative stress and antioxidant defense genes in the kidney of
      inbred mice after intestinal ischemia and reperfusion.
AB  - PURPOSE: To determine the gene expressions profile related to the oxidative
      stress and the antioxidant response in the kidneys of mice subjected to
      intestinal ischemia and reperfusion. METHODS: Twelve inbred mice (C57BL/6) were
      randomly assigned to one of two groups: the control group (CG) underwent
      anesthesia and was observed for 120 min and the ischemia/reperfusion group (IRG),
      animals were anesthetized and subjected to laparotomy and ischemia for 60 minutes
      followed by 60 minutes of reperfusion. The expressions of 84 genes from the
      kidney were determined by the Reverse Transcription qualitative Polymerase Chain
      Reaction (RT-qPCR). All genes that were up regulated by more than threefold using
      the algorithm [2(DeltaDeltaCt)] were considered statically significant (p<0.05).
      RESULTS: In the IRG group 29 (34.52%) of 84 genes, were up regulated by more than
      threefold. The genes that were differentially up regulated in the glutathione
      peroxidase cluster (10 genes): were Gpx2 and Gpx7. The genes that were up
      regulated in the peroxidase cluster (16 genes) were following: Duox1, Epx, Lpo,
      Mpo, Ptgs2, Rag2, Serpinb1b, Tmod1 and Tpo. The genes that up regulated in the
      reactive oxygen species cluster (16 genes): Il19, Il22, Nos2, Nox1, Noxa1, Noxo1,
      Recql4 and Sod2. The genes that were up regulated in the oxidative stress cluster
      (22 genes) were: Mpp4, Nudt15, Upc3 and Xpa. The genes that were up regulated in
      the oxygen carriers cluster (12 genes) were: Hbq1, Mb, Ngb, Slc38a1 and Xirp1.
      The peroxiredoxins genes (10) showed no consistent differential regulation.
      CONCLUSION: The genes related to oxidative stress and antioxidant defense showed
      increased expression in renal tissue trigged intestinal ischemia and reperfusion.

PMID- 24316859
TI  - Filling of extraction sockets of feline maxillary canine teeth with autogenous
      bone or bioactive glass.
AB  - PURPOSE: To evaluate bone healing in the extraction socket of the feline
      maxillary canine tooth after grafting. METHODS: Eighteen adult cats were
      submitted to unilateral extraction of maxillary canine tooth and divided into
      three groups. In group 1 (n=6), control, the extraction socket was left empty. In
      group 2 (n=6), the extraction socket was filled with autogenous cancellous bone
      from the iliac crest and in group 3 (n=6), with bioactive glass particulate
      material. Cats were euthanized at four weeks postoperative. RESULTS: The
      radiographic examinations performed four weeks after surgery showed that in all
      groups the healing process converged to a radiopacity similar to that observed in
      the surrounding bones. Histological examination showed formation of woven bone
      within the extraction socket. The percentage of newly formed bone within the
      extraction socket, measured by the histometry, showed no statistically
      significant difference among the values of the three groups (Kruskal-Wallis'test
      p>0.05) (group 1: 63.96 +/- 5.85, group 2: 66.84 +/- 11.67, group 3: 59.28 +/-
      15.50). CONCLUSION: The bone regeneration observed in the extraction sockets
      filled with autogenous cancellous bone or bioactive glass was similar to that
      observed in the control sites, given an observation period of four weeks after
      extraction of the maxillary canine tooth.

PMID- 24316860
TI  - Effects of the topical administration of copaiba oil ointment (Copaifera
      langsdorffii) in skin flaps viability of rats.
AB  - PURPOSE: To evaluate the effects of copaiba oil ointment (Copaifera langsdorffii)
      on dorsal skin flaps in rats. METHODS: Adult male rats (n=30) were distributed
      into three groups of ten animals each, as follows: GC--control; GCA--absolute
      control and GT--treated with copaiba ointment. The rats were subjected to dorsal
      cutaneous skin flap surgery and the animals from the GC and GT received post
      operative treatment for eight consecutive days. The animals from the GCA group
      did not receive treatment while the animals from the GC group received daily
      topical treatment of ointment without the active ingredient and the animals from
      the GT group were daily treated with 10% copaiba oil ointment. At the end of each
      experimental period the lesions were evaluated according to the percentage of
      necrotic area. Then, fragments from cranial, median and caudal parts were fixed
      in Bouin's solution and processed for paraffin embedding. The morphology of
      histological sections (5um) was evaluated and the number of leucocytes,
      fibroblasts and blood vessels was also analyzed. The data obtained were submitted
      to ANOVA test complemented by Tukey-Kramer test (p<0.05). RESULTS: The necrotic
      area was lower in the group treated with copaiba ointment when compared to the
      control groups (GCA>GC and GT), while the morphology showed larger granulation
      tissue with bulky fibroblasts and collagen fibers more arranged in the GT group.
      The morphometry showed a significant higher number of blood vessels in the median
      and caudal parts (GT>GCA and GC), leucocytes in the cranial part (GT>GC>GCA), and
      also fibroblasts in the median (GT and GC> GCA) and caudal parts (GT>GC and GCA)
      (p<0.05). CONCLUSION: The copaiba oil ointment favors angiogenesis and
      accelerates the viability of random skin flaps in rats.

PMID- 24316861
TI  - An alternative approach to deal with the absence of clinical trials: a
      proportional meta-analysis of case series studies.
AB  - PURPOSE: Systematic reviews are criticized for frequently offering inconsistent
      evidences and absence of straightforward recommendations. Their value seems to be
      depreciated when the conclusions are uncertain. To describe an alternative
      approach of evaluating case series studies in health care when there is absence
      of clinical trials. METHODS: We provide illustrations from recent experiences.
      Proportional meta-analysis was performed on surgical outcomes: (a) case series
      studies, (b) use of cryoablation or radiofrequency ablation, and (c) patients
      with small renal cell carcinoma. The statistically significant difference between
      both interventions studied was defined if their combined 95% confidential
      interval (CI) did not overlap. RESULTS: As demonstrated by the example, this
      analysis is an alternative approach to provide some evidence of the
      intervention's effects under evaluation and plotting all available case series in
      the absence of clinical trials for the health field. CONCLUSIONS: Although we are
      leading to a low level of evidence to determine efficacy, effectiveness and
      safety of interventions this alternative approach can help surgeons, physicians
      and health professionals for a provisionally decision in health care along with
      their clinical expertise and the patient's wishes and circumstances in the
      absence of high-quality primary studies. It's not a replacement for the gold
      standard randomized clinical trial, but an alternative analysis for clinical
      research.

PMID- 24316862
TI  - Reply to the letter to the editor entitled "the prognostic role of serum total
      bilirubin in non-ST-segment elevation myocardial infarction: what about on
      admission cardiovascular medications?" by Dr Canpolat.

PMID- 24316863
TI  - Rationale for full-season dosing for passive antibody prophylaxis of respiratory
      syncytial virus.
AB  - Palivizumab monthly injections throughout the RSV season prevent severe
      respiratory syncytial virus (RSV) disease in preterm infants <= 35 wGA. However,
      some RSV guidelines currently recommend stopping palivizumab after 3 months of
      age in the midst of the RSV season. This article evaluates the need for full
      season dosing by reviewing the pharmacokinetic properties of palivizumab and RSV
      hospitalization (RSVH) risk as a function of chronologic age. Precise human
      palivizumab protective levels are not established. Clinical trials show
      significant interpatient variability in palivizumab serum trough concentrations.
      Partial season dosing is associated with increased risk of RSVH. For late-preterm
      infants, data suggest that the risk of RSVH remains elevated through at least 6
      months of age. Monthly, full-season palivizumab dosing provides the only
      empirically proven protection from RSVH. In conclusion, late-preterm infants are
      at significant risk for RSVH through at least 6 months of age and would benefit
      from dosing throughout the RSV season. 

PMID- 24316864
TI  - The antagonistic effect of the sigma 1 receptor ligand (+)-MR200 on persistent
      pain induced by inflammation.
AB  - OBJECTIVE AND DESIGN: The sigma 1 (sigma1) receptor, which is widely distributed
      in the CNS in areas that are known to be important for pain control, may play a
      role in persistent pain characterized by the hypersensitivity of nociceptive
      transmission. Here, we investigated the effect of sigma1 blockade in an
      inflammatory pain model. TREATMENT AND METHODS: An intraplantar injection of
      carrageenan (2 %) was used to induce paw inflammation. The effects of the sigma1
      antagonist (+)-MR200, given subcutaneously at a dose of 0.1, 0.25, 0.5,1, 1.5,
      and 2 mg/kg prior to injection of carrageenan, on inflammatory pain and
      inflammation were assessed. Mechanical allodynia with von Frey filaments, thermal
      hyperalgesia with the plantar test and edema evaluation with a plethysmometer
      were measured. Intergroup comparisons were assessed by one- or two-way analysis
      of variance when appropriate, followed by post-hoc tests (Dunnett's test for one
      way or Bonferroni for two-way ANOVA). RESULTS: (+)-MR200 dose-dependently
      prevented allodynia and hyperalgesia induced by carrageenan. Furthermore, it
      reduced paw edema with a significant inhibition percentage of 37.82 % at 3 h
      after carrageenan treatment. CONCLUSIONS: The blockade of the sigma1 receptor
      with the selective antagonist (+)-MR200 may contribute to the suppression of the
      typical symptoms of inflammatory pain.

PMID- 24316865
TI  - Bradykinin in health and disease: proceedings of the Bradykinin Symposium 2012,
      Berlin 23-24 August 2012.

PMID- 24316866
TI  - Histamine induces chemotaxis and phagocytosis in murine bone marrow-derived
      macrophages and RAW 264.7 macrophage-like cells via histamine H4-receptor.
AB  - OBJECTIVE: Expression and function of histamine H4-receptor, an immunomodulatory
      receptor involved in inflammatory diseases, on murine macrophages, which are
      vital for immunity, were investigated. MATERIALS AND METHODS: The expression
      pattern of histamine receptors on bone marrow-derived macrophages of BALB/c mice
      and on RAW 264.7 cells was studied at the mRNA level by reverse transcription
      polymerase chain reaction. The functional relevance of histamine receptors was
      investigated by analyzing histamine-induced chemotaxis and phagocytosis in the
      presence of histamine receptor antagonists mepyramine (histamine H1-receptor),
      famotidine (histamine H2-receptor), thioperamide (histamine H3/4-receptors) and
      JNJ7777120 (histamine H4-receptor). RESULTS: Both bone marrow-derived macrophages
      and RAW 264.7 cells express mRNA for histamine H1-receptor and histamine H4
      receptor. Residual amounts of histamine H2-receptor mRNA are found in bone marrow
      derived macrophages only. In both cellular models, histamine induced chemotaxis
      and phagocytic activity, which was reduced by thioperamide as well as by JNJ
      7777120, but not by mepyramine or famotidine. CONCLUSION: In murine bone marrow
      derived macrophages and RAW 264.7 macrophage-like cells histamine H4-receptor
      mediates chemotaxis and phagocytic activity.

PMID- 24316868
TI  - Doing the best with what we have: we need better: informing obstetric policy with
      administrative data.

PMID- 24316867
TI  - Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells.
AB  - OBJECTIVE: The coxsackie and adenovirus receptor (CAR) mediates the entry of
      coxsackievirus B (CVB) and adenovirus into host cells and is, therefore, a key
      determinant for the molecular pathogenesis of viral diseases such as myocarditis.
      The aim was to investigate the influence of HMG-CoA reductase inhibitor
      lovastatin on CAR expression in endothelial cells. METHODS: Human umbilical vein
      endothelial cells (HUVECs) were exposed to different concentrations of lovastatin
      (0.05-5 MUmol/l) for up to 48 h. Alterations in CAR expression were examined by
      quantitative real-time PCR (qRT-PCR) and flow cytometry. In addition, after
      treatment with 1 MUmol/l lovastatin for 48 h, HUVECs were infected for 8 h with
      CVB3 and virus replication was detected by qRT-PCR using viral-specific TaqMan
      probes. RESULTS: We found that lovastatin decreases CAR mRNA expression by up to
      80% (p < 0.01) and CAR protein expression by up to 19% (p < 0.01), in a
      concentration-dependent manner. Moreover, virus replication of CVB3 was
      significantly inhibited after lovastatin treatment (p < 0.05). The signaling
      mechanism of CAR down-regulation by lovastatin depends on the Rac1/Cdc42 pathway.
      CONCLUSION: This study shows for the first time that lovastatin reduces the
      expression of CAR and subsequently the replication of CVB3 in HUVECs.

PMID- 24316870
TI  - Insurance coverage and prenatal care among low-income pregnant women: an
      assessment of states' adoption of the "Unborn Child" option in Medicaid and CHIP.
AB  - BACKGROUND: The "Unborn Child" (UC) option provides state Medicaid/Children's
      Health Insurance Program (CHIP) programs with a new strategy to extend prenatal
      coverage to low-income women who would otherwise have difficulty enrolling in or
      would be ineligible for Medicaid. OBJECTIVES: To examine the association of the
      UC option with the probability of enrollment in Medicaid/CHIP during pregnancy
      and probability of receiving adequate prenatal care. RESEARCH DESIGN: We use
      pooled cross-sectional data from the Pregnancy Risk Assessment Monitoring System
      from 32 states between 2004 and 2010 (n = 81,983). Multivariable regression is
      employed to examine the association of the UC option with Medicaid/CHIP
      enrollment during pregnancy among eligible women who were uninsured preconception
      (n = 45,082) and those who had insurance (but not Medicaid) preconception (n =
      36,901). Multivariable regression is also employed to assess the association
      between the UC option and receipt of adequate prenatal care, measured by the
      Adequacy of Prenatal Care Utilization Index. RESULTS: Residing in a state with
      the UC option is associated with a greater probability of Medicaid enrollment
      during pregnancy relative to residing in a state without the policy both among
      women uninsured preconception (88% vs. 77%, P < 0.01) and among women insured
      (but not in Medicaid) preconception (40% vs. 31%, P < 0.01). Residing in a state
      with the UC option is not significantly associated with receiving adequate
      prenatal care, among both women with and without insurance preconception.
      CONCLUSIONS: The UC option provides states a key way to expand or simplify
      prenatal insurance coverage, but further policy efforts are needed to ensure that
      coverage improves access to high-quality prenatal care.

PMID- 24316869
TI  - Rural-urban differences in obstetric care, 2002-2010, and implications for the
      future.
AB  - BACKGROUND: Approximately 15% of the 4 million annual US births occur in rural
      hospitals. OBJECTIVE: To (1) measure differences in obstetric care in rural and
      urban hospitals, and to (2) examine whether trends over time differ by rural
      urban hospital location. RESEARCH DESIGN AND SUBJECTS: This was a retrospective
      analysis of hospital discharge records for all births in the 2002-2010 Nationwide
      Inpatient Sample, which constitutes 20% sample of US hospitals (N = 7,188,972
      births: 6,316,743 in urban hospitals, 837,772 in rural hospitals). MEASURES:
      Rates of low-risk cesarean (full-term, singleton, vertex pregnancies; no prior
      cesarean), vaginal birth after cesarean (VBAC), nonindicated cesarean, and
      nonindicated labor induction were estimated. RESULTS: In 2010, low-risk cesarean
      rates in rural and urban hospitals were 15.5% and 16.1%, respectively, and
      nonindicated cesarean rates were 16.9% and 17.8%, respectively. VBAC rates were
      5.0% in rural and 10.0% in urban hospitals in 2010. Between 2002 and 2010, rates
      of low-risk cesarean and nonindicated cesarean increased, and VBAC rates
      decreased in both rural and urban hospitals. Nonindicated labor induction was
      less frequent in rural versus urban hospitals in 2002 [adjusted odds ratio = 0.79
      (0.78-0.81)], but increased more rapidly in rural hospitals from 2002 to 2010
      [adjusted odds ratio = 1.05 (1.05-1.06)]. In 2010, 16.5% of rural births were
      induced without indication (12.0% of urban births). CONCLUSIONS: From 2002 to
      2010, cesarean rates rose and VBAC rates fell in both rural and urban hospitals.
      Nonindicated labor induction rates rose disproportionately faster in rural versus
      urban settings. Tailored clinical and policy tools are required to address
      differences between rural and urban hospitals.

PMID- 24316871
TI  - Optimal staffing to prevent nursing home hospitalizations.

PMID- 24316872
TI  - Mechanical and physical properties of calcium silicate/alumina composite for
      biomedical engineering applications.
AB  - The focus of this study is to investigate the effect of Al2O3 on alpha-calcium
      silicate (alpha-CaSiO3) ceramic. alpha-CaSiO3 was synthesized from CaO and SiO2
      using mechanochemical method followed by calcinations at 1000 degrees C. alpha
      CaSiO3 and alumina were grinded using ball mill to create mixtures, containing 0
      50w% of Al2O3 loadings. The powders were uniaxially pressed and followed by cold
      isostatic pressing (CIP) in order to achieve greater uniformity of compaction and
      to increase the shape capability. Afterward, the compaction was sintered in a
      resistive element furnace at both 1150 degrees C and 1250 degrees C with a 5h
      holding time. It was found that alumina reacted with alpha-CaSiO3 and formed
      alumina-rich calcium aluminates after sintering. An addition of 15wt% of Al2O3
      powder at 1250 degrees C were found to improve the hardness and fracture
      toughness of the calcium silicate. It was also observed that the average grain
      sizes of alpha-CaSiO3 /Al2O3 composite were maintained 500-700nm after sintering
      process. 

PMID- 24316873
TI  - Revealing the structural and mechanical characteristics of ovine teeth.
AB  - The survival and function of dentition over the lifetime of an animal depends
      upon the ability of the teeth to resist wear and chemical erosion, and to
      withstand occlusal loading conditions without suffering debilitating fracture.
      Understanding how geometrical factors (radius, height, enamel thickness) and
      mechanical properties of the dental tissues (Young's modulus E, hardness H and
      toughness KIC of enamel and dentin) combine to ensure the survival of an animal's
      teeth can provide great insight into the evolutionary history of the animal and
      its dietary adaptation. While the geometrical factors are beginning to be
      understood, the range of animals for which measurements of dental tissue
      properties are available is very narrow, being restricted almost entirely to
      humans and other primates. The absence of comparative data across a broader range
      of species makes it impossible to draw conclusions with any certainty. The
      present study expands knowledge of mammalian dental tissue properties by
      reporting the Young's modulus and hardness of ovine (sheep) enamel and dentin
      measured using nano-indentation. We found that sheep molar enamel Young's modulus
      and hardness are both lower than those of human enamel, by approximately 30%, and
      9% respectively, while the properties of dentin are similar. The combination of E
      and H makes the ovine enamel approximately 30% more resistant to wear than human
      enamel, which is an imperative in ruminant dentition. The results of this study
      are interpreted in terms of the ovine feeding ecology, and the structure of the
      ovine molar and its occlusal surface. 

PMID- 24316874
TI  - Frequency and diameter dependent viscoelastic properties of mitral valve chordae
      tendineae.
AB  - This study aimed to characterise viscoelastic properties of different categories
      of chordae tendineae over a range of frequencies. Dynamic Mechanical Analysis
      (DMA) was performed using a materials testing machine. Chordae (n=51) were
      dissected from seven porcine hearts and categorised as basal, marginal, strut or
      commissural. Chordae were loaded under a sinusoidally varying tensile load at a
      range of frequencies between 0.5 and 5Hz, both at a standardised load (i.e. same
      mean load of 4N for all chordae) and under chordal specific loading (i.e. based
      on in vivo loads for different chordae). Storage modulus and stiffness were
      frequency-dependent. Loss modulus and stiffness were frequency-independent.
      Storage and loss moduli, but not stiffness, decreased with chordal diameter.
      Therefore, strut chordae have the lowest moduli and marginal chordae the highest
      moduli. The hierarchy of dynamic storage and loss moduli is: marginal,
      commissural, basal and strut. In conclusion, viscoelastic properties of chordae
      are dependent on both frequency and chordal type. Future/novel replacement
      chordal materials should account for frequency and diameter dependent
      viscoelastic properties of chordae tendineae. 

PMID- 24316876
TI  - [The Elegy for National Health Service].

PMID- 24316875
TI  - HAF drives the switch of HIF-1alpha to HIF-2alpha by activating the NF-kappaB
      pathway, leading to malignant behavior of T24 bladder cancer cells.
AB  - Hypoxia is a characteristic feature of solid tumors, leading to malignant
      behavior. During this process, HIF family members (HIFs) and the NF-kappaB
      pathway are activated. In addition, the hypoxia-associated factor (HAF) is
      reported to participate in the regulation of HIFs. However, the precise
      relationship among HIFs, HAF and the NF-kappaB pathway in bladder cancer (BC)
      remains unknown. In the current investigation, T24 BC cells were exposed to
      hypoxia, or by plasmid transfection to overexpress HAF or RelA (P65) to
      demonstrate their roles. The results indicate that hypoxia leads to the elevation
      of HAF plus activation of the NF-kappaB pathway, accompanied by the switch of HIF
      1alpha to HIF-2alpha, resulting in the enhanced ability of malignancy in T24
      cells. In order to further demonstrate the significance of this switch, HIF
      1alpha and HIF-2alpha were co-transfected into T24 cells with HIF-beta,
      respectively. The following results indicate that the T24hif-2alpha/beta cells
      show enhanced ability of malignancy, accompanied by the maintenance of stem-cell
      markers, but the T24hif-1alpha/beta cells show higher expression of metabolism
      related genes. Boyden assays and wound-healing assays indicate the enhanced
      ability of malignancy for T24hif-2alpha/beta. Thus, we conclude that on the
      hypoxic microenvironment, the switching of HIF-1alpha to HIF-2alpha, which is
      driven by HAF through activating the NF-kappaB pathway, contributes to the
      malignancy of T24 cells, accompanied by the maintenance of stem-cell markers.
      This provides us an avenue for understanding the progression of bladder cancer.

PMID- 24316877
TI  - [New role for hospital department directors in a Milan hospital, Italy].
AB  - In Italy, the hospital departmental model was introduced over 30 years ago with
      the aim of fostering collaboration between wards and promoting the appropriate
      use of resources. However, these objectives have not been consistently met. For
      this reason, the Strategic Direction of the hospital "Fondazione IRCCS Ca' Granda
      Ospedale Maggiore Policlinico" in Milan has proposed a new model in which
      department directors are given a more active role in hospital management and
      actively participate in decision-making processes.

PMID- 24316878
TI  - [Control and prevention of tuberculosis in healthcare facilities].
AB  - Tuberculosis remains the leading cause of death by a single infectious agent.
      Healthcare workers who for professional reasons are exposed to infectious
      patients and to potentially contaminated materials are at high risk of infection.
      This article provides a review of existing regulations and summarizes national
      and international guidelines and operational protocols for tuberculosis
      surveillance in clinical settings. 

PMID- 24316879
TI  - [The social responsibility report drafting in healthcare facilities. Experiences
      in Fatebenefratelli's Hospitals].
AB  - Medical facilities have the duty to report, in a transparent, comprehensive and
      integrated manner, their performance, not only in relation to the services
      provided directly but also in relation to the interest of the various
      stakeholders and the economic and social benefits for the community. The Social
      Report is not only a communication tool related to corporate social
      responsibility but also the initial basis for acquiring social legitimacy, and
      serves the role of "social accounting" of the activities of an organization, with
      respect to its mission and institutional role. In healthcare, it can contribute
      to achieving the fundamental objectives of the healthcare system, in the
      financial area (fair financing), and also in the medical (outcomes) and ethical
      social areas. 

PMID- 24316880
TI  - [Frequency of food-borne infections in an Italian region, before and after
      abolishing food worker health cards, 1996-2009].
AB  - The authors present and discuss the results of a study performed in an Italian
      region, to compare the frequency of food-borne infections before and after
      abolishment of food worker health card requirements. Results confirm the efficacy
      of food safety training for food handlers, in accordance with evidence-based
      prevention data. 

PMID- 24316881
TI  - [Educational interventions in patients with heart failure: a review of the
      literature].
AB  - Patient education is recognized as a central component of heart failure care and
      reduces hospital readmissions. Nurses have an important role in providing patient
      education and modifying self-care behaviors. The aim of this article is to
      examine characteristics of educational interventions for heart failure patients,
      their measured outcomes and the role of nurses in providing education. We
      conducted a literature review of the last 10 years and considered 30 articles.
      Multisession motivational interventions, repeated over time and with different
      follow-up interventions seem to produce the best results. However, some aspects
      remain controversial. 

PMID- 24316882
TI  - Livestock and microbiological risk (a review).
AB  - The presence of pathogens in animal manure depends on several factors such as,
      for example, the species, age, type of power supply, state of health, methods and
      times of storage, treatments administered. Currently there are no specific
      requirements for the minimum sanitary standards of livestock manure to be used in
      agriculture, or even of the digestate resulting from anaerobic digestion, such as
      cattle slurry and plant matrices (e.g. maize). While there are some indications
      for products fermented aerobically (compost deriving also from manure) and the
      sludge resulting from wastewater treatment and intended for use as fertilizers.
      In this paper we sum up the information given in the scientific literature on the
      viability of some microorganisms and on the effects of the anaerobic digestion of
      livestock manure and plant matter, such as maize, on the microbial
      concentrations. 

PMID- 24316883
TI  - [Vaccines and autism: a myth to debunk?].
AB  - Thanks to vaccinations the incidence of many seriously debilitating or life
      threatening diseases and the resulting infant mortality or disability have been
      drastically reduced. In populations, who are no more aware of the risk of these
      infections, the attitude of suspicion and fear towards the vaccinations is
      expanding and in some cases reaches a worldwide media coverage as was the case
      for the measles, mumps and rubella vaccine (MMR). In 1998, a British doctor,
      Andrew Wakefield, and co-authors, published in "Lancet" a study in which he
      suggested the existence of "a new variant of autism" associated with intestinal
      inflammation. He proposed the administration of the MMR vaccine as a possible.
      cause of the inflammatory process. The hypothesis suggested by Wakefield led to a
      drastic drop in vaccination coverage in the UK and to the failure to achieve
      adequate levels of immunization in many countries, with a consequent increase in
      the incidence of measles and its complications. Wakefield work stimulated a broad
      discussion in the scientific community and many studies conducted over the next
      few years contradicted the research results of the English physician. In 2004,
      journalist Brian Deer conducted an accurate investigation that revealed how the
      Wakefield research presented many not regular aspects and was performed with
      predominantly economic objectives. In 2010, Wakefield was expelled from the
      General Medical Council, while the "Lancet" retracted the paper. The scientific
      research conducted in recent years confirm the inconsistency of the relationship
      between MMR vaccine and autism. The possible association with other factors, such
      as autoimmune processes, hyperactivation of mast cells in the hypothalamus, use
      of paracetamol in genetically predisposed children are currently investigated.

PMID- 24316884
TI  - [Treatment of testicular cancer].
AB  - Germ-cell tumours (GCTs) are the most common type of cancer in young men. Since
      the late 1970s, disseminated GCT have been a paradigm for curable metastatic
      cancer and metastatic GCTs are highly curable with cisplatin-based chemotherapy
      followed by surgical resection of residual masses. Patients' prognosis is
      currently assessed using the International Germ-Cell Consensus Classification
      (IGCCC) and used to adapt the burden of chemotherapy. Approximately 20% of
      patients still do not achieve cure after first-line cisplatin-based chemotherapy,
      and need salvage chemotherapy (high dose or standard dose chemotherapy). Clinical
      stage I testicular cancer is the most common presentation and different
      strategies are proposed: adjuvant therapies, surgery or surveillance. During the
      last three decades, clinical trials and strong international collaborations lead
      to the development of a consensus in the management of GCTs. 

PMID- 24316885
TI  - New series of 6-substituted coumarin derivatives as effective factor Xa
      inhibitors: synthesis, in vivo antithrombotic evaluation and molecular docking.
AB  - Despite recent progress in antithrombotic therapy, there's still an unmet medical
      need for safe and orally available anticoagulants. Encouraged by the marked
      antithrombotic and anticoagulant activities of some coumarin derivatives, twenty
      three new N-coumarinyl-4-amidinobenzamides 4a-f and 6-heterocycle substituted
      coumarin derivatives 5, 6a,b, 10a-e, 12a-e and 14a-d were synthesized and
      evaluated for their in vivo antithrombotic activity. The most active congeners
      were the unsubstituted amidine 4a (36.5 s), coumarinyl oxadiazole 5 (42.3 s), bis
      coumarinyl oxadiazole 6b (37.8 s) and coumarinyl pyrazole 10b (38.5 s) that
      presented prothrombin time (PT) values comparable to the reference drug warfarin
      (42.3 s). Furthermore, docking studies were undertaken to gain insight into the
      possible binding mode of these compounds with the coagulation factor Xa (FXa)
      binding site. 

PMID- 24316886
TI  - A facile one-pot reduction method for the preparation of a SnO/SnO2/GNS composite
      for high performance lithium ion batteries.
AB  - A SnO/SnO2/GNS composite with controlled oxidation states and composition has
      been prepared through simple one-pot reduction of an EG suspension of SnCl2 and
      graphene oxide. The as-prepared composite was characterized by XRD, FT-IR, XPS,
      SEM, TEM and BET. SnO and SnO2 nanoparticles are uniformly distributed on the
      surface of the graphene. Taking advantage of the high electron conductivity of
      graphene and the large theoretical capacity of SnO, this SnO/SnO2/GNS composite
      exhibits high charge/discharge capacity, good cycling stability and good rate
      capability. A specific discharge capacity of approximately 464.2 mA h g(-1) is
      retained after being charged/discharged at a current density of 1000 mA g(-1) for
      30 cycles. 

PMID- 24316887
TI  - APTS and rGO co-functionalized pyrenated fluorescent nanonets for representative
      vapor phase nitroaromatic explosive detection.
AB  - For the first time, flexible PVP/pyrene/APTS/rGO fluorescent nanonets were
      designed and synthesized via a one-step electrospinning method to detect
      representative subsaturated nitroaromatic explosive vapor. The functional
      fluorescent nanonets, which were highly stable in air, showed an 81% quenching
      efficiency towards TNT vapor (~10 ppb) with an exposure time of 540 s at room
      temperature. The nice performance of the nanonets was ascribed to the synergistic
      effects induced by the specific adsorption properties of APTS, the fast charge
      transfer properties and the effective pi-pi interaction with pyrene and TNT of
      rGO. Compared to the analogues of TNT, the PVP/pyrene/APTS/rGO nanonets showed
      notable selectivity towards TNT and DNT vapors. The explored functionalization
      method opens up brand new insight into sensitive and selective detection of vapor
      phase nitroaromatic explosives. 

PMID- 24316888
TI  - Identification of a unique TGF-beta-dependent molecular and functional signature
      in microglia.
AB  - Microglia are myeloid cells of the CNS that participate both in normal CNS
      function and in disease. We investigated the molecular signature of microglia and
      identified 239 genes and 8 microRNAs that were uniquely or highly expressed in
      microglia versus myeloid and other immune cells. Of the 239 genes, 106 were
      enriched in microglia as compared with astrocytes, oligodendrocytes and neurons.
      This microglia signature was not observed in microglial lines or in monocytes
      recruited to the CNS, and was also observed in human microglia. We found that TGF
      beta was required for the in vitro development of microglia that express the
      microglial molecular signature characteristic of adult microglia and that
      microglia were absent in the CNS of TGF-beta1-deficient mice. Our results
      identify a unique microglial signature that is dependent on TGF-beta signaling
      and provide insights into microglial biology and the possibility of targeting
      microglia for the treatment of CNS disease. 

PMID- 24316891
TI  - Group for Research and Assessment of Psoriasis and Psoriatic Arthritis - GRAPPA
      (2003-2013).

PMID- 24316890
TI  - The missense of smell: functional variability in the human odorant receptor
      repertoire.
AB  - Humans have ~400 intact odorant receptors, but each individual has a unique set
      of genetic variations that lead to variation in olfactory perception. We used a
      heterologous assay to determine how often genetic polymorphisms in odorant
      receptors alter receptor function. We identified agonists for 18 odorant
      receptors and found that 63% of the odorant receptors we examined had
      polymorphisms that altered in vitro function. On average, two individuals have
      functional differences at over 30% of their odorant receptor alleles. To show
      that these in vitro results are relevant to olfactory perception, we verified
      that variations in OR10G4 genotype explain over 15% of the observed variation in
      perceived intensity and over 10% of the observed variation in perceived valence
      for the high-affinity in vitro agonist guaiacol but do not explain phenotype
      variation for the lower-affinity agonists vanillin and ethyl vanillin.

PMID- 24316889
TI  - Therapeutic activation of macrophages and microglia to suppress brain tumor
      initiating cells.
AB  - Brain tumor initiating cells (BTICs) contribute to the genesis and recurrence of
      gliomas. We examined whether the microglia and macrophages that are abundant in
      gliomas alter BTIC growth. We found that microglia derived from non-glioma human
      subjects markedly mitigated the sphere-forming capacity of glioma patient-derived
      BTICs in culture by inducing the expression of genes that control cell cycle
      arrest and differentiation. This sphere-reducing effect was mimicked by
      macrophages, but not by neurons or astrocytes. Using a drug screen, we validated
      amphotericin B (AmpB) as an activator of monocytoid cells and found that AmpB
      enhanced the microglial reduction of BTIC spheres. In mice harboring intracranial
      mouse or patient-derived BTICs, daily systemic treatment with non-toxic doses of
      AmpB substantially prolonged life. Notably, microglia and monocytes cultured from
      glioma patients were inefficient at reducing the sphere-forming capacity of
      autologous BTICs, but this was rectified by AmpB. These results provide new
      insights into the treatment of gliomas. 

PMID- 24316892
TI  - Subclinical atherosclerosis in ankylosing spondylitis: is there a role for
      inflammation?
AB  - OBJECTIVES: To evaluate the prevalence of subclinical atherosclerosis in patients
      with ankylosing spondylitis (AS) in comparison to controls with similar
      cardiovascular risk factors. METHODS: Forty-two consecutive patients with AS and
      42 controls matched for age (43.3 +/- 11.7 vs. 43.7 +/- 11.3, P = 0.89), gender,
      smoking, diabetes mellitus and arterial hypertension were enrolled. Participants
      were excluded if a personal cardiovascular disease (CV) history was present. A
      questionnaire recording demographic data, medical and medication history was
      fulfilled. Blood pressure, abdominal circumference, height and weight were
      measured. Lipid profile was determined in a 12-hour fastened blood sample.
      Ultrasound analysis of the common carotid artery was performed by one blind
      observer. The distance between the lumen-intima interface and the leading edge of
      the media-adventitia interface (IMT) was measured and participants were also
      evaluated for the presence of plaques. RESULTS: The comparative analysis of
      demographic and cardiovascular risk factors between AS patients and controls did
      not reveal statistically significant differences. Also, no significant
      differences between groups were observed for TC, HDL-C, T-C/HDL-C, LDL-C,
      triglycerides, or dyslipidemia frequency. IMT measures were not different in AS
      and controls (0.62 +/- 0.09 vs. 0.61 +/- 0.09, P = 0.39) as well as plaques
      frequencies (19% vs. 17%, P = 0.78). CONCLUSIONS: Subclinical atherosclerosis
      assessed through carotid ultrasound imaging was not more prevalent in the AS
      group when compared to controls with similar cardiovascular risks. Our
      observations may imply that CV risk factors may have more influence on the CV
      system than AS itself. These findings should be confirmed in a larger population
      with a prospective study design.

PMID- 24316893
TI  - EpiFibro--a nationwide databank for fibromyalgia syndrome: the initial analysis
      of 500 women.
AB  - INTRODUCTION: Fibromyalgia syndrome (FS) is a common painful condition of the
      musculoskeletal system that is typically accompanied by several symptoms in other
      systems. In Brazil, the prevalence of FS is estimated at 2.5%. Here, we present
      the initial data from Epi-Fibro, a nationwide databank of FS patients seen in
      public and private settings. OBJECTIVE: The aims of this study were to assess how
      the diagnosis of FS was made, identify a set of clinical domains considered
      relevant by both clinicians and patients in cases of FS, analyse the impact of
      disease on patient quality of life, and compare the findings among patients of
      public and private services. METHODS: Based on the results of questionnaires, we
      analysed data corresponding to the first 500 women in the database.
      Questionnaires pertaining to demographic and clinical data and the Fibromyalgia
      Impact Questionnaire (FIQ), which was translated and validated for Brazilian
      patients, were completed by the clinicians and/or patients. RESULTS: Preliminary
      analysis of the EpiFibro databank revealed that female FS patients in Brazil
      reported a high impact of disease, as measured by the FIQ, a high prevalence of
      associated symptoms, and a low degree of education (consistent with the public
      health care in Brazil used mainly by the underserved). In addition, most patients
      perceived their pain as diffuse from the onset of disease. CONCLUSION: Depression
      and anxiety were seen as the main triggers of FM symptoms, but a significant
      proportion of the subjects perceived work strain as the initial trigger.We also
      observed a delay of a few years in seeking medical help and examination by a
      rheumatologist.

PMID- 24316894
TI  - Radiographic changes of cervical spine in rheumatoid arthritis.
AB  - INTRODUCTION: The involvement of the cervical spine is a common feature of
      rheumatoid arthritis (RA). OBJECTIVE: To study the prevalence of radiographic
      changes of the cervical spine in patients with RA and their association with
      clinical and serological profiles of the disease. METHODS: We analysed lateral
      (neutral position, hyperextension, hyperflexion) and transoral views of cervical
      spine radiographs from 80 individuals with RA to investigate the presence of
      atlanto-axial subluxation (AAS), basilar invagination (BI), and subaxial
      instability (SAI). Demographic, clinical (nodules, interstitial pneumonitis,
      secondary Sjogren's syndrome, medications etc.), and serologic (rheumatoid factor
      -RF, cyclic citrullinated peptide antibody--anti-CCP, and antinuclear factor-
      ANF) data were obtained from the clinical records. RESULTS: Cervical spine
      misalignments were identified in 26/80 (32.5%) participants; AAS occurred in
      12/80 (15%) participants, BI in 6/80 (7.5%), and SAI in 13/80 (32.5%). Odontoid
      erosions were identified in 16/80 (20.0%) participants. Cervical spine
      misalignment exhibited associations with age at onset and disease duration (P =
      0.03 and 0.02, respectively). No associations were identified between the
      cervical spine changes and the participants' ethnicity or gender, presence of
      nodules, interstitial pneumonitis, secondary Sjogren's syndrome, RF, ANF, or anti
      CCP. The participants with cervical spine misalignment exhibited higher
      frequencies of odontoid erosion (P = 0.03). CONCLUSIONS: Cervical spine
      misalignment was a common radiographic finding and occurred more frequently in
      participants with earlier onset and longer length of RA.

PMID- 24316895
TI  - Physical activity among patients from the Brasilia cohort of early rheumatoid
      arthritis.
AB  - INTRODUCTION: The 2012 Consensus of the Brazilian Society of Rheumatology (SBR)
      for the treatment of Rheumatoid Arthritis (RA) recommends that patients should
      regularly perform physical exercises. There have been no studies in Brazil on
      physical activity among patients with early RA. OBJECTIVE: To investigate the
      physical activity practice among patients with early RA and the possible
      association between physical activity, disease activity and functional
      disability. METHODS: Cross-sectional study of patients from the Brasilia cohort
      of early RA. Demographic data (sex, age and level of schooling), physical
      activity practice, Disease Activity Score 28 (DAS 28), functional disability
      (Health Assessment Questionnaire - HAQ), as well as data on smoking status,
      alcohol consumption, comorbidities and RA treatment were analyzed. RESULTS: A
      total of 72 patients were evaluated, 90.27% females, mean age 50.2 +/- 13.3
      years, mean DAS 28: 3.66 and HAQ: 0.69. Of them, 43.05% were regularly active,
      with walking being the most often practiced exercise (80.64%). The mean duration
      of exercise was 48.22 +/- 27.18 min, with a frequency of 3.7 +/- 1.64 times per
      week. There was no association between physical activity and gender, age,
      educational level, disease activity, functional disability, alcoholism or
      smoking, presence of comorbidities and treatment with drugs that alter the course
      of disease. CONCLUSION: Given the importance of regular physical activity
      practice, it is necessary to recommend it to patients, especially resistance
      physical activities, which are not frequent among the patients in our study.

PMID- 24316896
TI  - Evaluation of platelet aggregation in the presence of antiphospholipid
      antibodies: anti-beta2GP1 and anticardiolipin.
AB  - INTRODUCTION: The antiphospholipid syndrome (APS) is an autoimmune condition
      characterized by recurrent arterial and venous thrombosis, besides obstetric
      complications. The pathogenesis is associated with the presence of
      antiphospholipid and/or anti-b2-glicoprotein I (anti-b2GPI) antibodies that
      appear to change the anticoagulant activity of b2GPI. Antibody-induced
      dimerization of b2GPI seems to be related to the induction of platelet
      aggregation, contributing to the development of thrombosis in APS. OBJECTIVES:
      The objective of the present study is to demonstrate the influence of
      antiphospholipid antibodies in platelet aggregation tests with different agonists
      (ADP, collagen, and adrenaline). METHODS: We analyzed platelet aggregation tests
      with different agonists (ADP, collagen, adrenalin) when normal platelets were
      exposed to serum with different concentrations of antiphospholipid antibodies.
      RESULTS: Results demonstrated a significant inhibition in adrenalin- and ADP
      induced platelet aggregation curves (P < 0.05) in all antibody concentrations
      tested when compared to the control. The paradox between the prothrombotic state
      and the presence of autoantibodies that show anticoagulant activity in vitro was
      demonstrated in the literature, making it difficult to understand the
      pathophysiologic mechanism of the antiphospholipid syndrome. CONCLUSION: Results
      showed that anticardiolipin and anti-b2GPI antibodies-rich serum, both of which
      belonging to the IgG class, can interfere with platelet aggregation curves.

PMID- 24316897
TI  - Symptoms of disease and psychological adaptation in Brazilian scleroderma
      patients.
AB  - OBJECTIVE: To characterize the prevalence and impact of symptoms of scleroderma
      in Brazilian patients and to describe their satisfaction with medical care and
      psychological symptoms. METHODS: One-hundred and twenty eight Brazilian
      scleroderma patients participated in an online survey by filling out a Portuguese
      version of the Canadian Scleroderma Patient Survey of Health Concerns and
      Research Priorities. The mean age of participants was 38 years old (SD = 12.33),
      and most of the participants were females (n = 108, 88%). RESULTS:
      Hardening/tightening of skin, itchy skin and joint pain were symptoms reported as
      being most frequent, whereas muscle pain and difficulty climbing stairs were
      symptoms reported as having a higher impact. Participants reported
      dissatisfaction regarding the medical care. Psychological evaluations suggested
      that participants who scored above clinical values for depression was
      significantly high (90%; n = 77). In addition, 48% (n = 42) of participants fit
      the clinical criteria for anxiety disorder, and 40% (n = 35) of participants fit
      the clinical criteria of social phobia. Finally, body image disturbance was
      reported by 69% (n = 88) of participants. CONCLUSIONS: The physical and
      psychological symptoms associated with scleroderma have a significant impact on
      patient quality of life. The Brazilian patients in the current sample report
      higher levels of dissatisfaction with medical care than patients from Canada and
      European countries. These Brazilian patients also report more psychopathology,
      particularly symptoms of depression. The current results suggest that there is a
      need for professionals to consider and attend to the individual problems of
      scleroderma patients.

PMID- 24316898
TI  - Usefulness of anti-dsDNA antibody screening with chemiluminescence followed by
      confirmation by indirect immunofluorescence.
AB  - OBJECTIVE: The purpose of this study was to evaluate the performance of a
      chemiluminescent immunoassay (CLIA) to detect anti-dsDNA antibodies, using the
      indirect immunofluorescence test (IIF) on Crithidia luciliae as a reference.
      METHODS: The automation system demonstrated 81% efficiency, 100% sensitivity and
      82% specificity according to the intrinsic validation process performed using 179
      consecutive samples from 169 patients in the beginning of 2011. These patients
      were subsequently divided into 3 groups according to the co-reactivity of anti
      dsDNA results using the 2 methods (reactive, non-reactive and discrepant
      results). RESULTS: Upon data analysis, 77% (129/169) of the tests were requested
      by rheumatologists, and 57% (97/169) of the samples were from lupus patients.
      Both the reactive and non-reactive results of the CLIA were well defined and
      standardised, and automation reduced the manual labor required by 70% in a safe
      and high-quality manner. Furthermore, the high prevalence of patients with lupus
      and nephritis among the CLIA false-positive results corroborates the hypothesis
      that the actual index of CLIA false positivity is lower than that initially found
      in this study.

PMID- 24316899
TI  - Adalimumab in rheumatoid arthritis treatment: a systematic review and meta
      analysis of randomized clinical trials.
AB  - Since the discovery of the role of tumor necrosis factor in the
      physiopathological process of rheumatoid arthritis, five drugs that block this
      cytokine have been used as therapeutic options. To evaluate the efficacy and
      safety of adalimumab in the treatment of rheumatoid arthritis we performed a
      systematic review and meta-analysis of randomized controlled trials. A search of
      relevant studies in Medline (through PubMed) and LILACS in June 2011 was carried
      out. Study selection, data collection and analysis were performed in pairs and
      independently by two reviewers and by a third reviewer in cases of disagreement.
      The meta-analysis was performed using the software Review Manager(r) 5.1 using
      the random effects model. Eleven articles related to adalimumab were included and
      considered nine studies with 3461 patients. Ten studies showed low risk of bias
      regarding the blinding of participants and personnel and blinding of outcome
      assessment. Patients who received the combination treatment of adalimumab and
      methotrexate showed better efficacy results and lower radiographic progression
      when compared to placebo + methotrexate in 24-104 weeks. Patients who received
      adalimumab as monotherapy showed better efficacy outcomes when compared to
      placebo in 24 and 26 weeks. The results of the meta-analyses of adverse events
      were not statistically significant, except for reactions at the injection site,
      which favored the control group. Adalimumab efficacy was demonstrated in
      monotherapy and when associated to a DMARD, but the evidence for combined use is
      more robust. 

PMID- 24316900
TI  - Psychiatric comorbidities in patients with systemic lupus erythematosus: a
      systematic review of the last 10 years.
AB  - OBJECTIVE: To analyze the frequency of psychiatric comorbidities in patients with
      systemic lupus erythematosus (SLE) using the systematic review method. METHODS: A
      systematic literature search was performed between April and July 2011 in the
      following databases: BIREME, PubMed and CAPES thesis database. This search
      prioritized studies published over the last ten years (2001-2011), involving the
      presence of psychiatric comorbidities in patients with SLE. RESULTS: Out of 314
      articles published in scientific journals (PubMed) and 29 (BIREME), previously
      identified ones, 13 articles on psychiatric disorders and SLE were selected so
      they could be submitted to the systematic review methodological approach. The
      articles indicated high frequency of psychiatric comorbidities, especially mood
      and anxiety disorders. There is no consensus between the disease activity and
      psychiatric disorders. Patients with active SLE showed a higher risk of
      developing mood disorders than patients with inactive SLE. CONCLUSION: Patients
      with SLE had a higher suicide risk than the general population. More thorough
      studies to evaluate the psychological and genetic role, specific and non-specific
      autoimmune inflammatory mechanisms in mood and anxiety disorders are needed.

PMID- 24316901
TI  - Bullous systemic lupus erythematosus in a pregnant woman: a case report.
AB  - Systemic lupus erythematosus (SLE) can cause numerous skin lesions. Despite being
      rare, lupus-specific bullous lesions demonstrate characteristic clinical and
      immunopathological features and require differential diagnosis among numerous
      bullous conditions that may overlap with SLE. The present study presents a case
      of bullous systemic lupus erythematosus (BSLE) in a pregnant woman. 

PMID- 24316902
TI  - c-ANCA associated vasculitis in patients with ulcerative colitis: case report.
AB  - The pulmonary manifestations of ulcerative colitis (UC) are rare and include
      inflammation of small and large airways, parenchymal disease and serositis among
      others. A substantial proportion of patients with inflammatory bowel disease,
      particularly those with ulcerative colitis presents positive ANCA, most p-ANCA
      pattern. We present a case of patient with ulcerative colitis, with positive c
      ANCA, which progressed to hemoptysis associated with radiological findings
      consistent with pulmonary vasculitis. 

PMID- 24316903
TI  - Lipid profile and anti-TNF-alpha use.
AB  - The use of anti-TNF-alpha has been associated with several changes in lipid
      profile, although some study results are conflicting. The knowledge of this fact
      is of great importance when one observes at the association between rheumatic
      diseases and accelerated atherogenesis. The aim of this analysis was search for
      changes in lipid profile in anti TNF-alpha users in the population of Southern
      Brazil and its association with duration of use, indications, patient gender and
      type of anti-TNF. For this purpose, we studied the profiles of total cholesterol
      (TC), HDL cholesterol (HDLc), LDL cholesterol (LDLc), atherogenic index (ATI) and
      triglycerides (TGs) of 58 patients (42 with rheumatoid arthritis and 16 with
      spondyloarthritis) before and after using this drug for a median of 16.0 months.
      There were no changes in the levels of TC, HDLc, LDLc and ATI (P = NS). However,
      there was a significant increase in TG levels (P = 0.03). The median difference
      between first and second TG measurements was 16 mg/dL and this increase was not
      associated with gender, time of use, use indication or type of anti TNF-alpha (P
      = NS). It was concluded that the use of anti TNF-alpha is associated with
      increased values of TG. 

PMID- 24316904
TI  - The use of ustekinumab in refractory treatment of psoriatic arthritis.

PMID- 24316905
TI  - Pitfalls in the biopsy diagnosis of intraoral minor salivary gland neoplasms:
      diagnostic considerations and recommended approach.
AB  - Among the more common types of intraoral minor salivary gland neoplasms are
      pleomorphic adenoma, basal cell adenoma, polymorphous low-grade adenocarcinoma,
      and adenoid cystic carcinoma. These minor salivary gland neoplasms share similar
      morphologic features and to a large extent immunohistochemical findings.
      Differentiation between these benign and malignant neoplasms is often predicated
      on the presence or absence of invasion. As such, in the presence of limited
      tissue sampling that typifies the initial testing modalities, including fine
      needle aspiration biopsy and/or incisional biopsy, it often is not possible to
      differentiate a benign from malignant minor salivary gland neoplasm. The
      diagnostic difficulties arise from the absence in needle or incisional biopsy of
      the tumor's periphery to determine whether infiltrative growth is or is not
      present. In this manuscript we discuss limitations and considerations associated
      with evaluation of incisional biopsies of intraoral minor salivary gland tumors.
      We offer a diagnostic approach to evaluating these biopsies, and suggest
      diagnostic terminology for biopsy specimens in which distinction between
      benignancy and malignancy is not feasible. The pathologist's approach to this
      distinction is critical, as treatment of benign neoplasms is generally
      conservative, whereas malignant lesions may warrant more aggressive management. 

PMID- 24316906
TI  - SATB2 is a novel marker of osteoblastic differentiation and colorectal
      adenocarcinoma.
AB  - SATB2 is a nuclear matrix-associated transcription factor and epigenetic
      regulator that is involved in osteoblastic differentiation and is also expressed
      in the glandular epithelial cells of the lower gastrointestinal tract. Recent
      studies have shown that, because of its relative specificity for osteoblastic
      differentiation, SATB2 immunostaining could potentially be a useful adjunct for
      assisting in the differential diagnosis of both benign and malignant osteogenic
      tumors. In addition, because SATB2 is also a highly sensitive and specific marker
      for colorectal adenocarcinomas, it could also serve as a complementary marker in
      the differential diagnosis of a carcinoma of unknown primary origin. 

PMID- 24316907
TI  - Hodgkin lymphoma: pathology, pathogenesis, and a plethora of potential prognostic
      predictors.
AB  - Hodgkin lymphoma (HL) encompasses 2 unique clinicopathologic entities, classical
      Hodgkin lymphoma (CHL) (~95% of cases) and nodular lymphocyte predominant HL (~5%
      of cases). Both subtypes demonstrate a paucity of surreptitious (in CHL)
      neoplastic B cells within a background of reactive inflammatory cells
      underscoring both the relatedness of these 2 entities to each other, as well as
      their distinction from other types of lymphoid neoplasia. Clinically, they are
      primarily nodal diseases that disseminate in a predictable manner to contiguous
      nodal regions. The biology of HL as a whole, as well as the genetic and
      pathologic features that distinguish CHL from nodular lymphocyte predominant HL
      and other lymphomas has been the subject of a wealth of investigation in recent
      decades. The aim of this review is to detail the pathologic features of HL and to
      highlight the recent insights into its molecular basis and the myriad prognostic
      markers being described. 

PMID- 24316908
TI  - Update on the cytologic and molecular features of medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) accounts for only 5% to 10% of all thyroid
      carcinomas, but it is the most aggressive form of well-differentiated thyroid
      carcinoma, being responsible for 8% to 15% of all thyroid cancer-related deaths.
      MTC is frequently diagnosed at a locally advanced or metastatic stage, and 10
      year survival rates in these cases are <20%. Fine-needle aspiration biopsy of the
      thyroid gland is an accurate method to diagnose MTC, having a high sensitivity
      and specificity. The cytologic features of MTC are characteristic and the
      cytologic diagnosis of classic MTC is often straightforward, especially when
      combined with immunocytochemistry. However, because of its morphologic
      heterogeneity and overlap with other tumors, the differential diagnosis of MTC on
      cytology and on histology is broad with several potential pitfalls. Significant
      advances have been made over the last decade in understanding MTC. This concerns
      mainly the early detection of MTC, especially in familial forms (eg, multiple
      endocrine neoplasia type 2), and the identification of key molecular pathways and
      alterations which now offer promising targets for specific therapies in
      progressive MTC cases. Genetic testing (eg, RET mutation) has allowed for early
      detection in asymptomatic carriers and high-risk patients, with prophylactic
      thyroidectomy often being curative. Targeted therapies with multityrosine-kinase
      inhibitors (eg, vandetanib or cabozantinib) have emerged as promising new
      treatments for recurrent or metastatic MTC. In this review article, we discuss
      the cytologic features of MTC and its variants, its differential diagnosis, the
      role of ancillary studies, and the salient molecular features of MTC. 

PMID- 24316909
TI  - The journey toward personalized cancer therapy.
AB  - Human cancer has been one of the most difficult and tenacious problems that has
      defied many therapeutic regimens in the past. In recent years, there has been an
      explosive growth in our knowledge about molecular cell biology of cancer leading
      to the development of several molecularly targeted therapies. These therapeutic
      agents are used specifically for those tumors that are found to be susceptible to
      such a therapeutic approach. These therapies include a variety of monoclonal
      antibodies that target cell-surface receptors or, in some cases, their ligands. A
      second type of targeted therapies consists of small molecules that are designed
      to inhibit tyrosine kinase activity within the cancer cells. Despite initial
      optimism, this approach to cancer therapy is proven to be problematic because of
      inherent cancer heterogeneity and frequent development of drug resistance. The
      targeted therapies have improved survival time for many cancer patients but have
      not provided any definitive cures. The treating physicians constantly face the
      daunting challenge of balancing expected benefit with risk for complications, to
      achieve the most successful outcome. Still, the results often fall short of
      expectations. Personalized cancer treatment on the basis of targeted therapies is
      certainly an achievable goal, but more work is needed to make it a reality. 

PMID- 24316910
TI  - Innovative therapies in Ewing Sarcoma.
AB  - Ewing Sarcoma is a developmental tumor characterized by balanced chromosomal
      translocations and formation of new fusion genes, which are the main hallmark of
      this rare entity. Despite the vast knowledge regarding the molecular aspects of
      this rare malignancy obtained in the last few years, including the discovery of
      new therapeutic targets, many questions still remain open. In this review we
      focus on the research on targeted therapies in this malignancy, and discussed
      some bottlenecks related to this such as the possible role of pathologists, the
      availability of samples, the lack of appropriate animal models, and the resources
      needed to carry out preclinical and clinical research. 

PMID- 24316911
TI  - Comparison of dual-source parallel radio frequency transmission liver MRI at 3.0
      T with conventional MRI.
AB  - AIM: Aim of the present study was to investigate the role of dual-source parallel
      Radio frequency (RF) and single-source excitation in liver imaging at 3.0 T MR.
      METHODS: This study was a retrospective analysis. One hundred and seven subjects
      underwent a 3.0 T TX MR scanning including axial spectrally selective attenuated
      inversion recovery (SPAIR) T2WI, axial DWI and coronal balanced-fast field echo
      (Balanced FFE). Each sequence was carried out with both single-source and dual
      source RF excitation. Student's t test was used to compare whether there was
      difference between single-source and dual-source RF excitation in the image
      uniformity, single-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).
      Wilcoxon signed rank test was used to determine whether there was difference
      between conventional and parallel transmission in the score of image quality.
      Reader agreement was assessed using the Cohen's Kappa test. RESULTS: For the
      image uniformity, there was significant difference between single-source and dual
      source excitation (418.40+/-66.75 for single-source vs. 416.26+/-50.61 for dual
      source, t=2.524, P<0.05). There also existed significant difference between
      single-source and dual-source excitation in SNR and CNR, respectively. The SNR
      and CNR of parallel transmission (22.03+/-12.16 and 18.33+/-10.01, respectively)
      were both higher than those of single transmission (20.36+/-11.21 and 15.22+/
      8.95, respectively) (t=-2.630, P<0.05 for SNR and t=-4.238, P<0.05 for CNR).
      Image quality comparisons revealed significantly better results with dual-source
      than single-source RF excitation at SPAIR T2WI (1.4+/-0.42 vs. 1.81+/-0.27), DWI
      (1.08+/-0.46 vs. 1.63+/-0.36) and balanced FFE sequence (0.95+/-0.45 vs. 1.65+/
      0.37, Z=-5.894, -5.801 and -6.985, respectively, P<0.01). In the comparison of
      image quality, the agreement between the two readers was very good (Kappa>0.8,
      P<0.05). CONCLUSION: Dual-source parallel RF excitation MR imaging in liver
      enables reducing dielectric shading, improving homogeneity of the RF magnetic
      induction field, and increasing SNR and CNR at 3.0 T.

PMID- 24316912
TI  - Correlation of myocardial performance index assessed by different
      echocardiographic methods in patients with acute myocard infarction receiving
      different reperfusion treatment.
AB  - AIM: Myocardial performance index (MPI) is a well known prognostic parameter in
      acute myocardial infarction (AMI) patients, which has been used to assess global
      cardiac functions. In this study, we aimed to evaluate the corelation between the
      MPI levels obtained by PW doppler and Tissue doppler ultrasonography with
      reperfusion in AMI patients. METHODS: Fifty-four consecutive acute ST elevatation
      myocardial infarction patients, 26 treated with primary percutaneous coronary
      intervention (PCI) and 28 with thrombolytic therapy (TT); and 15 consecutive
      healthy controls were included in the study. MPI levels were measured with pulsed
      wave (PW) doppler and tissue Doppler ultrasonography in all patients. The
      isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT) and
      ejection time (ET) values used to measure MPI levels were determined. Corelation
      between the time intervals obtained with both methods were evaluated. MPI
      variations were evaluated in patients treated with PCI and TT. A significant
      corelation was observed in MPI levels obtained with PW doppler and tissue doppler
      ultrasonography (P<0.001) as well as between IRT, ICT and ET values (for all
      parameters; P<0.001). No significant corelation was observed between the MPI
      levels obtained with PW doppler and tissue doppler ultrasonography in patients
      treated with primary PTCA and TT (P=0.128, P=0.991, respectively). A significant
      corelation was observed between the MPI values obtained by PW doppler and tissue
      doppler ultrasonography with reperfusion interval (P=0.002, P<0.001,
      respectively). CONCLUSION: As a result, tissue Doppler ultrasonography may be
      used as an alternative to PW doppler to evaluate MPI, which is a well known
      prognostic factor in AMI. No relation has been observed between MPI values in
      early phases of AMI with reperfusion pattern, while a connection has been
      observed between MPI and reperfusion interval.

PMID- 24316913
TI  - Blood pressure during nocturnal sleep in headache.
AB  - AIM: Interactions between blood pressure control, sleep and headache have been
      largely studied, although not well understood. We designed a study trying to
      simultaneously evaluate all three aspects in the same subjects. We particularly
      concentrated on the observation of physiological blood pressure circadian rhythm,
      and the presence of cutaneous allodynia correlated to headache. Objective of the
      study was to investigate blood pressure during nocturnal sleep in patients that
      underwent a blood pressure 24 hours monitoring, and at the same time the presence
      of headache and of sleep behavioural alterations. METHODS: Blood pressure 24
      hours monitoring was performed by an ambulatory blood pressure (ABP) monitor
      (Space Labs) with its ad hoc software. Headache diagnosis was made according to
      ICHD-II criteria. Presence of allodynia and sleep behavior were evaluated through
      semi-structured ad hoc questionnaires. RESULTS: A total of 195 subjects were
      included, of which 122 without headache (mean age 60.4+/-11.6 years, 78 men and
      44 women) and 73 with history of headache, (mean age 54.2+/-12.5 years, 18 men
      and 55 women). Fifty-one headache patients had migraine (mean age 52.6+/-11.7
      years, 11 men and 40 women) and 22 tension type headache (TTH - mean age 58.0+/
      13.5 years, 7 men and 15 women). Allodynia was found in 30 out of 73 headache
      patients: 23 out of 51 in the migraine group and in 7 out of 22 in the tension
      type one. The physiological reduction of blood pressure during night (dipping)
      was more conserved among headache patients (34 dippers out of 73 subjects, 46,6%)
      with respect to subjects without headache (40 dippers out of 122, 32,8%) and that
      this border-line difference was more strongly significant comparing allodynic
      subjects (19 dippers out of 30, 63.3%) with both non-headache (40 dippers out of
      122, 32.8%, P<0.001) and non-allodynic (15 out of 43, 34.9%, P<0.05) ones. No
      significant difference was observed between headache patients and subjects
      without headache in terms of mean systolic and diastolic pressure, neither
      between migraine and TTH. CONCLUSION: Allodynic headache patients seem to
      maintain a more physiologic pressure circadian rhythm. While considering the
      possibility of selection bias, the hypothesis of an allostatic function of
      headache and allodynia in patients with unbalanced blood pressure could be made.

PMID- 24316914
TI  - Glomerular filtration rate: which method should we measure in daily clinical
      practice?
AB  - AIM: In this study, we compared estimated glomerular filtration rate (eGFR)
      calculated with the formulas of Cockcroft-Gault (C&G), Modification of Diet in
      Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      and Mayo Clinic Quadratic (Mayo Q) and, GFR (mGFR) that was scintigraphically
      measured with creatinine clearance (CrCl) and technetium-99m diethylene triamine
      penta-acetic acid (99mTc-DTPA). Objective of this study was to define the
      correlations between the formulas, provide a reliable method for measurement and
      estimation of GFR in daily clinical practice and demonstrate the potential
      errors. METHODS: C&G, CKD-EPI, Mayo Q and MDRD eGFR of 84(37 males, 47 females)
      patients diagnosed with chronic kidney disease were calculated. Values of 99mTc
      DTPA based on mGFR were compared with eGFR values of the formulas. RESULTS:
      Significant correlations were found with the values of 99mTc-DTPA mGFR, CrCl,
      MDRD, CKD-EPI, Mayo Q and C&G eGFR. The highest correlation was found between
      LBM(lean body mass) corrected C&G, MDRD-6, Mayo Q and CKD-EPI eGFR. The best
      estimate was made with MDRD-6 in the cases with 99mTc-DTPA mGFR<30 mL/min/1.73
      m(2) and with MDRD-4 in the cases with 99mTc-DTPA mGFR>=30 mL/min/1.73 m(2),
      while the worst estimate was made with uncorrected C&G formula in both groups.
      CONCLUSION: All eGFR formulas can be used in daily clinical practice. However,
      using MDRD-6 in the cases with GFR<30 mL/min/1.73 m(2) and MDRD-4 in the cases
      with GFR>=30 mL/min/1.73m(2) as well as using LBM for C&G eGFR or correction
      according to LBM when AW (actual weight) is used, might provide a more accurate
      estimation.

PMID- 24316915
TI  - Relationship between ultrasonography and electromyography measurement of
      abdominal muscles when activated with and without pelvis floor muscles
      contraction.
AB  - AIM: The importance of the abdominal musculature in spine stability, has promoted
      the development of a variety of studies. Ultrasound imaging (UI) is a valuable
      tool which, when applied appropriately, has the potential to provide significant
      insight into abdominal muscle contraction. Limited studies have been taken place
      regarding the relationship between ultrasound measures of muscle thickening and
      electromyography (EMG) measures of activation. Inconsistent results, however,
      have been reported. Based on previous studies association between abdominal
      muscle activation and thickening may be affected by contraction level. The aims
      of this study were to measure the relationship between abdominal muscle thickness
      and abdominal muscles amplitude in different levels of abdominal muscles
      contraction. METHODS: The research was carried on with a convenience sampling at
      the Physical Therapy Department of University of Social Welfare and
      Rehabilitation Sciences. Thirty healthy participants volunteered for this study.
      Muscle thickness right transversus abdominis (TrA) and obliqus internus (OI)
      muscles in abdominal hallowing maneuvers with and without pelvic floor muscle
      (PFM) contraction has been measured. Additionally, surface EMG of the right
      TrA/IO muscles was recorded. A hardware electrical part that acts as trigger
      system was used to record the activities of abdominal muscles in UI and EMG
      synchronously. Thickness change, normalized thickness and maximum amplitude
      abdominal muscles were used for statistical analysis. RESULTS: Correlations
      between the thickness change and amplitude measures were -0.03 -- 0.38 for
      TrA/IO. The Correlations between the normalized thickness and amplitude measures
      were -0.04--0.26 for TrA/IO. CONCLUSION: There is not clear relationship between
      increases in abdominal muscle activation and corresponding measures of thickening
      during abdominal muscle contraction. Changes in thickness of deep abdominal
      muscle cannot be used to indicate changes in the electrical activity in this
      muscle.

PMID- 24316916
TI  - [Experience with 5% lidocaine medicated plaster in the treatment of localized
      neuropathic pain].
AB  - AIM: The aim of this paper is to confirm the efficacy and safety in clinical
      practice of 5% lidocaine medicated plaster (LMP) in the treatment of localized
      neuropathic pain. METHODS: Retrospective, observational study carried out in the
      period 2006-2012, in patients with various forms of localized peripheral
      neuropathic pain treated with LMP. Only patients with at least one follow-up
      visit after prescription of the drug were assessed. RESULTS: One hundred and one
      patients were assessable, 60.4% of whom suffered from postherpetic neuralgia
      (PHN), while the remainder reported mainly post-traumatic/post-surgical
      neuropathic pain and other superficial localized neuralgias. In baseline
      conditions, the mean pain intensity measured on the NRS was 6.1. The median
      treatment time with LMP was 41 days, at the end of which there was a 64% fall in
      NRS, with no significant differences between the patients with PHN or other
      localized neuralgias. A better NRS reduction trend was also observed in those
      patients who, in our study, started treatment with LMP from the first visit,
      compared with those patients to whom LMP was prescribed later. The tolerability
      was good, with few adverse events at the application site, which led to
      suspension of treatment in just three cases. CONCLUSION: In our experience, LMP
      proved to be an effective and well-tolerated drug in the treatment of PHN and
      other superficial localized neuralgias. This observation is in agreement with the
      international guidelines, which suggest LMP as first line treatment for the
      management of localized peripheral neuropathic pain.

PMID- 24316917
TI  - Risk assessment in patients with antiphospholipid antibodies.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the
      association of antiphospholipid antibodies (aPL) with thrombosis and/or pregnancy
      loss: classification criteria were defined in the updated international consensus
      held in Sidney in 2005. Vascular and obstetric manifestations display partially
      different pathogenetic mechanisms. Thrombosis develop as a result of local
      procoagulative changes upon triggers influence (second-hit theory). Pregnancy
      morbidity is thought to be dependent on placental thrombosis and complement
      activation. The laboratory tests include Lupus Anticoagulant (LA), a functional
      assay, and anticardiolipin (aCL) and anti-beta2-glycoprotein I antibodies
      detected by solid phase enzyme-linked immunosorbent assay (ELISA). The LA testing
      is relatively standardized while there's still significant interlaboratory
      discrepancy in ELISA tests. Current APS criteria are under discussion: since for
      vascular and obstetric APS, different pathogenetic mechanisms have been shown,
      some criteria variation could also be contemplated. What is the weight of aPL
      antibodies in provoking thrombosis and which contribution could be expected from
      aPL per se is debated. As thrombosis is generally considered to be multi
      factorial, each case needs a risk-stratified approach. Any primary prophylaxis,
      intensity and duration of secondary prophylaxis should take into account aPL
      profile, other cardiovascular risk factors and systemic autoimmune diseases
      associated. We look forward to the publication of recommendations of the leading
      experts in the field, developed during the recent 14th International Congress in
      Rio de Janeiro, Brazil. 

PMID- 24316918
TI  - [Multidisciplinar international classification of the severity of acute
      pancreatitis: Italian version 2013].
AB  - AIM: The aim of this paper was to present the 2013 Italian edition of a new
      international classification of acute pancreatitis severity. The Atlanta
      definitions of acute pancreatitis severity are ingrained in the lexicon of
      pancreatologists but suboptimal because these definitions are based on empiric
      description of occurrences that are merely associated with severity. METHODS: A
      personal invitation to contribute to the development of a new international
      classification of acute pancreatitis severity was sent to all surgeons,
      gastroenterologists, internists, intensivists, and radiologists who are currently
      active in clinical research on acute pancreatitis. A global web-based survey was
      conducted and a dedicated international symposium was organized to bring
      contributors from different disciplines together and discuss the concept and
      definitions. RESULTS: The new international classification is based on the actual
      local and systemic determinants of severity, rather than description of events
      that are correlated with severity. The local determinant relates to whether there
      is (peri)pancreatic necrosis or not, and if present, whether it is sterile or
      infected. The systemic determinant relates to whether there is organ failure or
      not, and if present, whether it is transient or persistent. The presence of one
      determinant can modify the effect of another such that the presence of both
      infected (peri)pancreatic necrosis and persistent organ failure have a greater
      effect on severity than either determinant alone. The derivation of a
      classification based on the above principles results in 4 categories of severity
      mild, moderate, severe, and critical. CONCLUSION: This classification provides a
      set of concise up-to-date definitions of all the main entities pertinent to
      classifying the severity of acute pancreatitis in clinical practice and research.

PMID- 24316919
TI  - Nanobioprobe mediated DNA aptamers for explosive detection.
AB  - Specific nucleic acid aptamers using the microtiter plate based modified SELEX
      method against explosive trinitrotoluene are reported. Efficient partitioning of
      dsDNA was carried out using streptavidin labeled gold nanoprobes for the
      selection of specific aptamers. The selected binders having an affinity of ~10(
      7) M were used in the newly developed electrochemical aptasensor, exhibiting a
      detection limit of around 1 ppb for trinitrotoluene.

PMID- 24316920
TI  - [Complications and related determinants in 13669 pregnant women].
AB  - OBJECTIVE: To investigate pregnancy complications and related determinants, and
      provide scientific evidence for maternal health care. METHODS: A total of 13669
      pregnant women who planned to deliver in the hospital were randomly identified
      and surveyed by questionnaire. Chi-square test and logistic regression models
      were used to screen the influencing factors for pregnancy complications. RESULTS:
      The incidence of pregnancy complication was 13.94%. The following diseases had
      higher incidence than others: anemia (2.95%), premature rupture of membranes
      (2.51%), diabetes (1.92%), severe preeclampsia (1.43%), mild preeclampsia
      (1.27%), and hypertensive disorder complicating pregnancy (1.27%). Data from
      logistic regression models showed that pregnancy complications were related to
      maternal age, education level, number of caesarean sections, ways to terminate
      pregnancy, gestation weeks and number of fetuses. CONCLUSION: The rate of
      pregnant complication is high, which should be treated in time to ensure the
      safety of pregnant women.

PMID- 24316921
TI  - [Influence of intrauterine hypoxia on the lung blood vessel development in rats
      after birth and expression of VEGF in the lung].
AB  - OBJECTIVE: To observe the effect of intrauterine hypoxia on the development of
      rat lung after birth under ordinary pressure and normoxia, on the expression of
      vascular endothelial growth factor (VEGF) in the lung as the age increasing after
      birth, and to provide experimental basis for the treatment of intrauterine
      hypoxia after baby was born. METHODS: Intrauterine hypoxia models were
      established. The rats were divided into an air-control group (the control group)
      and a hypoxic 6-day group (the hypoxic group). All rats were fed under normal
      pressure and normoxia after they were born. At postnatal 7, 14, and 21 days, we
      measured the pulmonary vascular morphometry, detected the expression of VEGF
      protein with immunohistochemisty, the expression of VEGF mRNA with real-time PCR,
      and observed the alteration of capillary endothelium in the lung tissues under
      the electron microscope. RESULTS: The expression of VEGF protein and VEGF mRNA in
      the 2 groups increased as the rats grew, but the expression increased slower in
      the hypoxic group than that in the control group. The increase curve of the 2
      groups crossed. There was no significant difference between the 2 groups in the
      pulmonary vascular morphometry at each experiment time point. Hyperplasia of
      capillary endothelium decreased with age. Cellular edema of capillary endothelium
      was obvious especially at the 14th day after birth under the electron microscope.
      CONCLUSION: The expression of VEGF protein and VEGF mRNA has slower increase in
      the intrauterine hypoxic rats than that in the normal control rats. The
      expression of VEGF may influence the development of lung vessel after rats was
      born.

PMID- 24316922
TI  - [Expression of Toll-like receptor 4 in cervical cell lines and cervical lesions
      and its relation to HPV16 infection].
AB  - OBJECTIVE: To explore the relation between human papillomavirus (HPV16) infection
      and expression of Toll-like receptor 4 (TLR4) in cervical cell lines and cervical
      lesion tissues and to investigate the effect of TLR4 on cervical cancer
      progression. METHODS: Expression of HPV16 E6 mRNA was detected by RT-PCR. Western
      blot and immunohistochemistry were used to detect the expression of TLR4 in H8,
      SiHa, Caski cell lines and formalin-fixed and paraffin-embedded cervical tissue
      specimens with cervicitis, cervical intraepithelial neoplasia (CIN) and cervical
      squamous cell carcinama (CSCC). DNA was extracted from paraffin-embedded cervical
      cancer tissues and HPV16 genes were detected. RESULTS: The differentiation
      expression of HPV16 E6 mRNA and TLR4 in SiHa and Caski was significantly higher
      than that of normal cervical cell H8 (P<0.05). The positive expression rates of
      TLR4 and HPV16 in chronic cervicitis, CIN, and cervical cancer were 32.0%, 59.4%,
      and 77.8% (P<0.01) and 8.0%, 48.4%, and 81.0% (P<0.01), respectively. Up
      regulation of TLR4 was correlated with tumor differentiation (P<0.01), but not
      with FIGO stages or lymph node metastasis (P>0.05). The expression of TLR4 was
      significantly correlated with HPV16 infection in CIN and CSCC (r=0.303, P<0.05,
      r=0.633, P<0.05). CONCLUSION: High expression of TLR4 may play important roles in
      the development and progression of CIN and CSCC, and the expression of TLR4 can
      be up-regulated by HPV16 infection.

PMID- 24316923
TI  - [Anti-sTn antibody 3P9 and B72.3 in serological diagnosis of endometrial
      carcinoma].
AB  - OBJECTIVE: To investigate the relationship between tumor-associated carbohydrate
      antigen sTn and endometrial carcinoma, and to evaluate the diagnostic value of 2
      test methods. METHODS: A total of 200 patients were enrolled, including 100
      subjects with endometrial carcinoma, 42 healthy nonpregnant women, 15 pregnant
      women without complications, and 43 patients with benign gynecologic diseases.
      The serum sTn-antigen concentrations were determined by 2 test methods (3P9
      combined with 4A6, and B72.3 combined with CC49). RESULTS: There was a
      significant difference in the value and the positive rate of sTn in the serum
      between the subjects and the contrasts (P<0.05). The sTn level in the pregnant
      women was high. The sTn level in the serum and its positive rate in endometrial
      carcinoma became higher with the clinical stage. 3P9 combined with 4A6 was better
      than B72.3 combined with CC49 in the detection of sTn in the serum as to
      sensitivity, specificity, positive-prediction, negative-prediction, and accuracy.
      CONCLUSION: The sTn antigen may become a new serological marker for the diagnosis
      of endometrial carcinoma, but pregnant women should be excluded. 3P9 combined
      with 4A6 is better than B72.3 combined with CC49 in the detection of sTn in the
      serum.

PMID- 24316924
TI  - [Expression of Notch3 and hypertensive renal fibrosis].
AB  - OBJECTIVE: To examine the expression of notch3 in the kidneys of patients with
      primary hypertension and rats with spontaneous hypertension, and to explore the
      relationship of notch3 and hypertension renal fibrosis. METHODS: Thirteen
      patients with primary hypertension served as a primary hypertension group (HP
      group), and 15 patients with kidney tumor served as a control group (CP group).
      The spontaneous hypertensive rats served as a primary hypertension group (SHR
      group, n=6), and WKY rats served as a control group (WKY group, n=6). Masson
      stainning was used to examine the collagen in the kidneys in the SHR group and
      the WKY group. Immunohistochemical staining was used to detect the levels of
      Notch3 in kidneys of the patients and the rats. The expression of snail mRNA in
      the kidneys in the SHR group and the WKY group was examined by real-time PCR.
      RESULTS: Masson staining showed much more collagen in the SHR group than that in
      the WKY group (P<0.05); the expression of Notch3 in the HP group was much higher
      than that in the CP group ( 6.741+/-0.231 vs 0.763+/-0.358, P<0.01). The
      expression of Notch3 in the SHR group was much higher than that in the WKY group
      (5.487+/-0.774 vs 0.421+/-0.163, P<0.01), and The expression of snail mRNA was
      much higher in the SHR group than that in the WKY group (0.996+/-0.120 vs 0.208+/
      0.090, P<0.01 ). CONCLUSION: Notch3 may be related to the occurrence of
      hypertension renal fibrosis.

PMID- 24316925
TI  - [Correlation between ABCC11 gene single nucleotide polymorphism and the incidence
      of axillary osmidrosis in Chinese Han population].
AB  - OBJECTIVE: To explore the relationship between ABCC11 gene single nucleotide
      polymorphism (SNP) and the incidence of axillary osmidrosis in Chinese Han
      population. METHODS: The genotype of ABCC11 gene SNP at rs17822931 in 40 patients
      with axillary osmidrosis and 5 normal Han people was detected and analyzed by
      high resolution melt and gene sequencing. RESULTS: The detection of the genotype
      of ABCC11 gene SNP at rs17822931 showed that: 37 of the 40 patients were GA
      genotype and the other 3 were GG genotype, while the 5 normal subjects were AA
      genotype. CONCLUSION: SNP in ABCC11 is the genetic cause of axillary osmidrosis.
      GG or GA leads to axillary osmidrosis, while AA allele presents the absence of
      axillary osmidrosis.

PMID- 24316926
TI  - [Regulation mechanism of eIF3 P170 on developing myocardial cell cycle].
AB  - OBJECTIVE: To investigate the expression of eIF3P170, cdc2, cyclinB1 and cyclinD1
      in developing cardiac myocytes, and the correlation between eIF3P170 with cdc2,
      cyclin D1, and cyclin B1 in mice. METHODS: Mouse cardiac myocytes were obtained
      at different time points. RT-PCR was employed to detect the expression of
      eIF3P170, cdc2, cyclin D1 and cyclin B1 mRNA. RESULTS: Expressions of eIF3P170,
      cdc2, cyclinD1 and cyclinB1 mRNA were higher in the embryonic Day 13, 15, 18 and
      postnatal Day 1, 2, 3, 5. Expressions at postnatal Day 5 reached the highest (all
      P values<0.05 vs other time points), and then the expressions of these genes
      gradually decreased to the weakest at postnatal Day 30 (all P values<0.05 vs
      other time points). The mRNA expression of eIF3P170 was positively correlated
      with cdc2, cyclin D1 and cyclin B1 mRNA expression respectively. CONCLUSION: The
      mRNA expressions of eIF3 P170, cdc2, cyclin D1 and cyclin B1 in the embryo and
      the early life after birth are high. They reach the maximum at postnatal Day 5,
      then gradually decreased.

PMID- 24316927
TI  - [Effect of ropivacaine on proliferation and migration of rat bone marrow
      mesenchymal stem cells].
AB  - OBJECTIVE: To observe the influence of ropivacaine on the proliferation and
      migration of rat bone marrow mesenchymal stem cells (BMSCs) and provide basis for
      the clinical application of BMSCs. METHODS: Rat BMSCs were isolated and cultured
      by adherence method. Surface markers of BMSCs were examined by flow cytometry.
      Multipotent differentiation of BMSCs was detected by induced adipogenesis,
      osteogenesis and muscular differentiation. Proliferation of BMSCs was examined by
      CCK-8 and Brdu incorporation after ropivacaine treatment at different
      concentrations. Migration of BMSCs was tested by cell scratch assay and Millicell
      experiment. RESULTS: Cultured cells had representative appearance and surface
      markers of BMSC, and they had potential multiple differentiation. Ropivacaine
      treatment at 50 and 100 MUmol/L significantly reduced the proliferation rate of
      BMSCs and Brdu incorporation rate. There was significant difference compared with
      the control group (P<0.05). Cellular scratch assay and migration experiment
      indicated that ropivacaine significantly reduced the migration of BMSCs. There
      was significant difference compared with the control group (P<0.05). All these
      mentioned effects of ropivacaine on BMSCs were dose-dependent. There was
      significant difference between groups (P<0.05). CONCLUSION: Ropivacaine can
      significantly reduce the proliferation and migration of rat BMSCs, suggesting
      that the influence of local anesthetics on BMSCs has to be taken into account
      when BMSCs are used in clinical practice.

PMID- 24316928
TI  - [Metabolic reprogramming in cancer: the art of balance].
AB  - Despite seminal studies in the 1920s by Warburg showing a characteristic
      metabolic pattern for tumors, cancer bioenergetics has often been relegated to
      the backwaters of cancer biology. Recent studies have shown that metabolism in
      the tumor tissue is far more complicated than we previously knew. Despite
      vigorous glycolysis, in fact, the tumor tissue still retains mitochondrial
      aerobic metabolism. Mitochondria is one of the main sites of the biosynthesis
      process of tumor cells. Recent studies revealed that abnormal fatty acid
      metabolism. Amino acid metabolism plays a key role in the tumorigenesis. The
      metabolic network in tumor cells was reprogrammed, leading to nutrition flux
      reorganization and re-direction. Metabolism reprogramming in tumor cells
      facilitates the balance between the needs of energy supply and the synthesis of
      biological macromolecules. Targeting cell metabolism is not intended to interfere
      the energy supply of tumor cells but to affect the synthesis of metabolic rate,
      thereby inhibiting the proliferation of the tumor. The review focuses on the
      importance of metabolic reprogramming in tumor development and cancer therapy. We
      summarize what is currently known about metabolic reprogramming and establish a
      framework to understanding its contribution to the altered metabolism of cancer
      cells. 

PMID- 24316929
TI  - [Self-management behaviors in patients with osteoarthritis].
AB  - Good self-management behaviors can control symptoms of the patients with
      osteoarthritis, improve the patients' joint function and quality of life.
      Patients' self-management behaviors have been impacted by disease knowledge, self
      efficacy, emotional state, and social support. All the above factors should been
      taken into full consideration when intervening. Self-management program is an
      intervention mode which can improve patient self-management behaviors and promote
      patient health. 

PMID- 24316930
TI  - [Effect of high glucose peritoneal dialysis solution on PGC-1alpha expression and
      mitochondria related oxidative injury in human peritoneal mesothelial cells].
AB  - OBJECTIVE: To investigate the mechanism of mitochondrial oxidative injury induced
      by high glucose peritoneal dialysis solution (PDS) and the protective effect of
      peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1alpha)
      in the mitochondria of human peritoneal mesothelial cells (HPMC) in the high
      glucose ambience. METHODS: HPMC was cultured in a PDS containing 1.5%, 2.5% and
      4.25% glucose for 24 hours. Western blot analysis was used to detect PGC-1alpha
      expression. MitoSOX? Red staining, respiratory chain complexes and antioxidant
      enzyme activities were determined. RESULTS: The activities of respiratory chain
      complex III and antioxidant enzymes decreased significantly in a concentration-
      and time-dependent manner, along with the increased production of mitochondrial
      reactive oxygen species (ROS) and cellular apoptosis. In addition, protein
      expression of PGC-1alpha was also decreased in the high glucose PDS ambience.
      CONCLUSION: High glucose PDS might inhibit PGC-1alpha expression, resulting in
      the inhibition of mitochondrial function and increase of mitochondrial ROS and
      cellular apoptosis.

PMID- 24316931
TI  - [Pre-conception factors for intrauterine growth retardation].
AB  - OBJECTIVE: To analyze the pre-conception factors for intrauterine growth
      retardation. METHODS: A nested case-control study was conducted in a cohort of
      1368 women from 14 Child and Maternity Health Care Departments by cluster
      sampling method in Liuyang City, Hunan Province. Following-up until delivery, we
      collected their medical records and maternal health care manual materials. All
      neonates with intrauterine growth retardation were detected in the follow-up (the
      case group) and another 186 neonates without intrauterine growth retardation,
      matched with gender and mother's age, were randomly selected from the cohort as
      controls. chi2 test and multiple conditional logistic regression were used to
      investigate the determinants of intrauterine growth retardation. RESULTS:
      Intrauterine growth retardation was associated with BMI (OR=64.775), waist
      circumference (OR=0.166), abortion (OR=6.997), level of total cholesterol
      (OR=0.045), folic acid (OR=0.077), and cortisol (OR=9.164). CONCLUSION:
      Intrauterine growth retardation is associated with BMI, waist circumference,
      abortion,level of total cholesterol, folic acid, and cortisol. Effective measures
      to reduce intrauterine growth retardation in children include strengthening the
      detection of pre-pregnancy blood biochemical indicators to guide health care
      during pregnancy, and increasing nutrition during pregnancy according to pre
      pregnancy BMI and waist circumference.

PMID- 24316932
TI  - [Association between CD24 polymorphism and genetic susceptibility to breast
      cancer: a case-control study].
AB  - OBJECTIVE: To evaluate the association between CD24 polymorphism and genetic
      susceptibility to breast cancer in Chongqing women of Han nationality. METHODS:
      In the case-control study, single nucleotide polymorphism of CD24 (rs3838646 and
      rs52812045) was genotyped by Sequenom MassArray(r)iPLEX GOLD System in 170
      patients with breast cancer and 178 healthy controls. Data were analyzed via t
      test, Chi-square test, and logistic regression analysis. RESULTS: The
      distribution of CD24 rs3838646 genotype and allelotype had no significant
      difference between the patients with breast cancer and healthy controls
      (chi2=3.54, P=0.17; chi2=2.29, P=0.13). Stratified by menstruation status,
      premenopausal individuals carrying CD24 rs3838646 Del allele significantly
      reduced the risk (OR=0.51, 95% CI 0.26-1.00, P=0.0485) of breast cancer compared
      with the individuals carrying CD24 CA/CA genotype. The distribution of CD24
      rs52812045 genotypes and allelotypes had no significant difference between the
      patients with breast cancer and healthy controls (chi2=5.37, P=0.07; chi2=3.05,
      P=0.08). Compared with C/C homozygotes, CD24 rs52812045 T/T homozygotes had a
      significantly reduced risk (OR=0.47, 95% CI 0.23-0.95; P=0.04) for breast cancer.
      CONCLUSION: CD24 polymorphism may be a marker for susceptibility to breast cancer
      in Han population in southwestern China. CD24 polymorphisms may be associated
      with a reduced risk of breast cancer in Chinese population. Further studies are
      needed to confirm these findings.

PMID- 24316933
TI  - [Constructing a p53-fused dual luciferase reporter and verifying its function].
AB  - OBJECTIVE: To construct a p53-fused dual luciferase reporter and to test whether
      this reporter can mimic wild-type p53 activities in a high-throughput screen.
      METHODS: A restriction endonuclease site was added to each terminus and the stop
      codon of the wild-type full-length p53 open reading frame (ORF) was removed by
      PCR. A restriction endonuclease site was added to each terminus and the start
      codon of the firefly luciferase ORF was removed by PCR. The two modified ORFs
      were inserted upstream of the IRES-induced renilla luciferase ORF in a CMV
      derived vector. The p53 fusion protein was expressed in cells to test its MDM2
      mediated degradation, subcellular localization, and induction of p53-responsive
      promoter. RESULTS: The p53-fused dual luciferase reporter was successfully
      constructed. After transfection into the host cells, the reporter expressing the
      p53 fusion protein that was degraded by oncoprotein MDM2, was mainly located
      inside the nucleus, and induced the p53-responsive promoter, respectively.
      CONCLUSION: The p53-fused dual luciferase reporter (p53FL/IRES/RL) can identify
      modulators of P53 protein level in a high-throughput screen of genetic or
      chemical libraries.

PMID- 24316934
TI  - [Lung MRI at 3T: comparison of CT and MRI in initial evaluation of pulmonary
      alveolar proteinosis].
AB  - OBJECTIVE: To explore whether the phospholipidoproteinaceous material deposit
      within the alveoli by a high-field 3T MRI has signal characters and its
      application for diagnosing pulmonary alveolar proteinosis. METHODS: A total of 11
      patients with pulmonary alveolar proteinosis previously diagnosed by fiberoptic
      bronchoscope lung biopsy underwent 64-slice helical CT scans and 3T MRI scans,
      and the CT scans and the MRI scans were compared. RESULTS: The
      phospholipidoproteinaceous material deposit within the alveoli presented longer
      or equal T1 relaxation time and longer T2 relaxation time, without characters of
      fatty or deposits of protein-like substance signals and enhancement. The
      distribution, form, number and size of the lesions at T2WI were almost the same
      as those at CT, the lesions were irregular in morphology, and there was a clear
      boundary between the lesions and the adjacent normal lung tissues. Dynamic
      contrast-enhanced MRI showed thickened pulmonary arteriolae and venulae in the
      lesions with more obviously thickened pulmonary venulae, which were in conformity
      with the pulmonary artery and venule enhancement. CT scan in 1 out of the 11
      cases showed lesions in both lungs mainly consisted of stripe-shaped and
      reticular structures, and no obvious sign of pulmonary alveolar proteinosis
      residue was found. MRI scan detected alveolar proteinosis that failed to be shown
      by CT scan. CONCLUSION: 3T MRI T2WI can easily detect the lesions of long T2
      signals formed by the lipoproteinaceous material deposit within the alveoli. In
      the lesions, geographic appearance was presented, and the crazy paving pattern
      was dimly visualized. MRI can reflect the morphological characters of PAP like CT
      and it is slightly better compared with CT in such aspects as evaluating the
      theraputic effect of lung lavage. As supplement to CT, high-field 3T MRI can
      serve as an important examination for lung diseases.

PMID- 24316935
TI  - [Effect of rehabilitation training on insulin-resistance and hippocampus amyloid
      beta peptide in rats with vascular dementia].
AB  - OBJECTIVE: To investigate the effect of rehabilitation training on insulin
      resistance and insulin degrading enzyme (IDE) in the hippocampus in rats with
      vascular dementia. METHODS: A total of 45 female Sprague-Dawley rats were
      randomly assigned into a rehabilitation group (n=15), an immobilization group
      (n=15), and a sham-operation group (n=15). The rats in the former 2 groups were
      operated on to establish the experimental vascular dementia model by bilateral
      common carotid artery permanent ligation. The rats' learning and memory were
      assessed 4 weeks after the operation. The plasma level of insulin was determined
      by ELISA at different time points after the operation. Immunohistochemical
      staining was used to detect the IDE expression in the hippocampus area. RESULTS:
      The rats in the rehabilitation group showed significantly better learning ability
      than that in the immobilization group (P<0.05). The plasma level of insulin in
      the rehabilitation group was lower than that in the immobilization group
      (P<0.05), IDE expression in the rehabilitation group was higher than that in the
      immobilization group (P<0.05) at 7 d and 28 d after the operation. CONCLUSION:
      Rehabilitation can accelerate the recovery of learning and memory in rats with
      vascular dementia, and the mechanism is possibly related to the amelioration of
      insulin resistance and increase of IDE expression in the hippocampus.

PMID- 24316936
TI  - [Effect of PD-WEBB training on balance impairment and falls in people with
      Parkinson's disease].
AB  - OBJECTIVE: To determine the effect of Parkinson's disease-weight bearing exercise
      for better balance (PD-WEBB) exercise on balance impairment and falls in people
      with Parkinson's disease (PD). METHODS: A single-blind, randomized controlled
      clinical trial was conducted. The falls efficacy scale score, unified Parkinson
      disease rating scale (UPDRS) score and Mini-BESTest score were measured and
      compared between a PD-WEBB group and a control group. RESULTS: The falls efficacy
      scale score, UPDRS-2 score, UPDRS-3 score and Mini-BESTest score were improved in
      the PD-WEBB group compared with the control group (P<0.05), with no significant
      change in UPDRS-1 score between the two groups. CONCLUSION: PD-WEBB training can
      significantly improve the balance impairment and quality of life to prevent
      falls. PD-WEBB training is suitable for PD patients in China, and is a
      reasonable, effective and sustainable training of family and community assessment
      model.

PMID- 24316937
TI  - Identification of novel inhibitors against Mycobacterium tuberculosis L-alanine
      dehydrogenase (MTB-AlaDH) through structure-based virtual screening.
AB  - Mycobacterium tuberculosis (MTB) the etiological agent of tuberculosis (TB)
      survives in the human host for decades evading the immune system in a latent or
      persistent state. The Rv2780 (ald) gene that codes for L-alanine dehydrogenase (L
      AlaDH) enzyme catalyzes reversible oxidative deamination of L-alanine to pyruvate
      and is overexpressed under hypoxic and nutrient starvation conditions in MTB. At
      present, as there is no suitable drug available to treat dormant tuberculosis; it
      is essential to identify drug candidates that could potentially treat dormant TB.
      Availability of crystal structure of MTB L-AlaDH bound with co-factor NAD+
      facilitated us to employ structure-based virtual screening approach to obtain new
      hits from a commercial library of Asinex database using energy-optimized
      pharmacophore modeling. The resulting pharmacophore consisted of three hydrogen
      bond donor sites (D) and two hydrogen bond acceptor sites (A). The database
      compounds with a fitness score more than 1.0 were further subjected to Glide high
      throughput virtual screening and docking. Thus, we report the identification of
      best five hits based on structure-based design and their in vitro enzymatic
      inhibition studies revealed IC50 values in the range of 35-80 MUM.

PMID- 24316938
TI  - Evaluation of reduced point charge models of proteins through Molecular Dynamics
      simulations: application to the Vps27 UIM-1-Ubiquitin complex.
AB  - Reduced point charge models of amino acids are designed, (i) from local extrema
      positions in charge density distribution functions built from the Poisson
      equation applied to smoothed molecular electrostatic potential (MEP) functions,
      and (ii) from local maxima positions in promolecular electron density
      distribution functions. Corresponding charge values are fitted versus all-atom
      Amber99 MEPs. To easily generate reduced point charge models for protein
      structures, libraries of amino acid templates are built. The program GROMACS is
      used to generate stable Molecular Dynamics trajectories of an Ubiquitin-ligand
      complex (PDB: 1Q0W), under various implementation schemes, solvation, and
      temperature conditions. Point charges that are not located on atoms are
      considered as virtual sites with a nul mass and radius. The results illustrate
      how the intra- and inter-molecular H-bond interactions are affected by the degree
      of reduction of the point charge models and give directions for their
      implementation; a special attention to the atoms selected to locate the virtual
      sites and to the Coulomb-14 interactions is needed. Results obtained at various
      temperatures suggest that the use of reduced point charge models allows to probe
      local potential hyper-surface minima that are similar to the all-atom ones, but
      are characterized by lower energy barriers. It enables to generate various
      conformations of the protein complex more rapidly than the all-atom point charge
      representation. 

PMID- 24316939
TI  - Ultraradical resection for locally recurrent rectal cancer.

PMID- 24316940
TI  - Simple interventions for complex complications: moving surgery forward.

PMID- 24316941
TI  - Practice parameters for the surgical treatment of ulcerative colitis.

PMID- 24316942
TI  - Prediction of response to preoperative chemoradiotherapy in rectal cancer by
      using reverse transcriptase polymerase chain reaction analysis of four genes.
AB  - BACKGROUND: Patients with rectal cancer exhibit a wide spectrum of responses to
      chemoradiotherapy. Several gene expression signatures have been reported to
      predict the response to chemoradiotherapy in rectal cancer, but the lack of
      practical assays has restricted the clinical use of this technique. OBJECTIVE: We
      aimed to identify a set of discriminating genes that can be used for the clinical
      prediction of response to chemoradiotherapy in rectal cancer. DESIGN AND
      SETTINGS: This study is a retrospective analysis of tumor samples in a single
      institute. PATIENTS: Sixty-two patients who underwent preoperative
      chemoradiotherapy were studied. MAIN OUTCOME MEASURES: Gene expression was
      initially studied in 46 training samples by microarray analysis, and the
      association between gene expression and response to chemoradiotherapy was
      evaluated. Quantitative reverse transcriptase polymerase chain reaction was
      performed to validate the microarray expression levels of the discriminating
      genes. We developed a gene expression model for the prediction of response to
      chemoradiotherapy based on the reverse transcriptase polymerase chain reaction
      findings and validated it by using 16 independent test samples. RESULTS: We
      identified 24 discriminating probes with expression levels that differed
      significantly between responders and nonresponders. Among 18 genes identified by
      Gene Symbol, real-time reverse transcriptase polymerase chain reaction showed
      significant differences in the expression of 16 genes between responders and
      nonresponders. We constructed a predictive model by using different sets of these
      16 genes, and the highest accuracy rate (89.1%) was obtained by using LRRIQ3,
      FRMD3, SAMD5, and TMC7. The predictive accuracy rate of this 4-gene signature in
      the independent set of 16 patients was 81.3%. LIMITATIONS: Validation in a
      different and large cohort of patients is necessary. CONCLUSIONS: The 4-gene
      signature identified in this study is closely associated with response to
      chemoradiotherapy in rectal cancer.

PMID- 24316943
TI  - Accuracy of preoperative MRI in predicting pathology stage in rectal cancers:
      node-for-node matched histopathology validation of MRI features.
AB  - BACKGROUND: Few studies that meticulously match individual lymph nodes seen on
      MRI with their precise histologic counterparts after total mesorectal excision
      have been reported. OBJECTIVE: The objective of this study was to determine
      whether preoperative MRI could detect lymph node metastases accurately in the
      node-by-node analysis. DESIGN: This was a prospective, observational cohort
      study. SETTINGS: The study was conducted at a tertiary-care hospital. PATIENTS:
      Forty patients with rectal cancer were enrolled. MAIN OUTCOME MEASURES: Specimens
      were assessed using MRI for clinical staging. After surgical resection of the
      tumor, the specimens were again imaged with ex vivo ultrasound scan to localize
      the perirectal node. The locations of each lymph node were precisely matched with
      its corresponding magnetic resonance image to enable a node-for-node comparison
      of magnetic resonance images and histologic findings. RESULTS: Agreement between
      MRI and histologic assessment of T stage was 82.5%. Of the 341 nodes harvested,
      120 were too small (<3 mm) to be depicted on magnetic resonance images, and 18 of
      these contained metastasis (15%). A correlation between the results of MRI and
      histopathology was feasible for 205 lymph nodes, and the overall success rate of
      matching between the 2 techniques was 91.1% (205 of 221). Preoperative MRI
      revealed a node-by-node sensitivity and positive predictive value of 58.0%, and
      61.7%. There was no difference in the diagnostic accuracy between the primary
      surgery subgroup and preoperative radiation subgroups. LIMITATIONS: The study is
      limited by its heterogeneity of cohorts including the subgroup with preoperative
      chemoradiation and the lack of preoperative ultrasound assessment. CONCLUSIONS:
      Preoperative MRI was moderately accurate for the prediction of mesorectal lymph
      node metastasis. Moreover, preoperative MRI was insufficient for detecting small
      lymph nodes (<3 mm) with metastasis.

PMID- 24316944
TI  - Metachronous serrated neoplasia is uncommon after right colectomy in patients
      with methylator colon cancers with a high degree of microsatellite instability.
AB  - BACKGROUND: Right-sided serrated polyps are precursors to sporadic microsatellite
      unstable colon cancers via the methylator pathway and have a high rate of
      synchronous and metachronous lesions. Serrated polyps also occur in Lynch
      syndrome, where right-sided microsatellite unstable cancers arise from germline
      mutations in mismatch repair genes. OBJECTIVE: The aim of this study was to
      compare serrated neoplasia in patients with sporadic and hereditary
      microsatellite unstable colon cancer and to examine the effect of right colectomy
      on the risk of metachronous polyps and cancers. DESIGN: This is a retrospective,
      descriptive, cohort study from database and chart review. SETTING: This study was
      conducted at a tertiary care hospital with a center for hereditary colorectal
      cancer. PATIENTS: Patients who had colon cancers with a high degree of
      microsatellite instability, methylator cancers, and Lynch syndrome cancers, were
      included. INTERVENTIONS: Interventions included colectomy, surveillance
      colonoscopy, and polypectomy. MAIN OUTCOME MEASURES: The primary outcomes
      measured were the incidence and location of metachronous polyps and cancers.
      RESULTS: Eighty-five patients were included: 47 with methylator cancers and 38
      with Lynch syndrome. Median ages at surgery were 75 years (range, 41-90) and 48
      years (range, 27-77), p < 0.0001. Forty-six (98%) patients with methylator
      cancers and 17 (45%) patients with Lynch syndrome underwent a right colectomy, p
      < 0.0001. Metachronous cancers occurred in 19/60 (32%) of patients with Lynch
      syndrome and no patients with methylator cancers, p < 0.0001. Thirty-four
      patients with methylator cancers had colonoscopic follow-up, with a median of 2
      colonoscopies per patient over a 32-month follow-up (range, 1-136). Sixty-three
      percent of patients with Lynch syndrome had colonoscopic follow-up, median of 4
      colonoscopies per patient over 102 months (range, 1-462), p < 0.0001. Four (9%)
      patients with methylator cancers each had 1 metachronous serrated polyp, compared
      with 10/37 (27%) patients with Lynch syndrome (p = 0.049), whose median number of
      polyps was 2 (range, 1-8). Characteristics of other associated polyps were
      similar between cohorts. LIMITATIONS: This study is somewhat limited by potential
      inherent bias from its retrospective design. Also, a high number of deaths in the
      CIMP+ cohort could have contributed to the low number of serrated polyps detected
      on colonoscopy surveillance, but given current understanding of serrated polyp
      growth, this may truly represent the left colon's tendency not to develop
      serrated polyps. CONCLUSIONS: Cancers with a high degree of microsatellite
      instability arise through 2 different molecular mechanisms. Metachronous serrated
      neoplasia, benign and malignant, following right colectomy in patients with the
      CpG-island methylator phenotype of colorectal cancer is uncommon. However, the
      colons of patients with Lynch syndrome are at high risk after segmental
      colectomy.

PMID- 24316945
TI  - Extended sacropelvic resection for locally recurrent rectal cancer: can it be
      done safely and with good oncologic outcomes?
AB  - BACKGROUND: A multimodality approach to patients with locally recurrent rectal
      cancer that includes surgery is associated with a significant survival advantage
      when tumor-free margins are achieved. Patients with advanced tumors will require
      extended sacropelvic resection to optimize oncologic outcomes. OBJECTIVE: The aim
      of this study was to assess the safety, feasibility, and oncologic outcomes of
      extended sacropelvic resection for locally recurrent rectal cancer at our
      institution. DESIGN: A retrospective review identified 406 patients who had
      surgery for locally recurrent rectal cancer between 1997 and 2007. From this
      group, all patients who underwent a curative-intent sacropelvic resection were
      analyzed. SETTINGS: This investigation was conducted at an academic tertiary
      referral center. PATIENTS: Thirty patients (24 male) were identified. Median age
      was 59 years (range, 25-84). Operations were performed for a first local
      recurrence (n = 24), a second recurrence (n = 5) and for a third recurrence (n =
      1). INTERVENTIONS: Twenty-six patients underwent neoadjuvant radiation, and 20
      received intraoperative radiation therapy. All patients underwent extended
      sacropelvic resection. MAIN OUTCOME MEASURES: The primary outcomes measured were
      early (<30 days) and late (>30 days) surgical complications. Overall and disease
      free survivals were estimated by using the Kaplan-Meier technique. RESULTS:
      Margin-negative resection was achieved in 93%. The most proximal level of spinal
      transection was the fourth lumbar space, and 4 patients underwent lower extremity
      amputation. There was no mortality, and early morbidity was seen in 76%. Median
      follow-up was 2.7 years (range, 2 months to 10.8 years). Overall survival at 2
      and 5 years was 86% and 46%. Disease-free survival at 2 and 5 years was 79% and
      43%. LIMITATIONS: This study was limited by its retrospective nature and the
      limited number of patients. CONCLUSIONS: We found extended sacropelvic resection
      for locally recurrent rectal cancer to be feasible and safe with overall and
      disease-free survival rates in comparison with survival rates seen in patients
      undergoing nonsacropelvic resections for locally recurrent rectal cancer.

PMID- 24316946
TI  - Prognostic factors and treatment effects in patients with curatively resected
      brain metastasis from colorectal cancer.
AB  - BACKGROUND: Colorectal cancer infrequently causes brain metastasis, and the
      prognosis is poor. OBJECTIVE: The aim of this study was to identify the
      prognostic factors associated with survival and outcome of treatment for patients
      with brain metastasis from colorectal cancer. DESIGN: This is a retrospective
      study from a prospectively collected database. SETTINGS: The investigation took
      place in a high-volume multidisciplinary tertiary cancer center in Japan.
      PATIENTS: From 1979 to 2010, 113 consecutive patients who were treated for brain
      metastasis from colorectal cancer were identified. MAIN OUTCOME MEASURES: The
      primary outcome measure was overall survival. RESULTS: Sixty-three patients had
      neurosurgical resection (including curative resection for 46 patients) followed
      by whole brain radiotherapy, 9 had stereotactic radiosurgery, 30 had whole brain
      radiotherapy, and 11 had steroid and palliative care. As a whole, the overall
      median survival time from diagnosis of brain metastasis was 5.4 months (95% CI,
      4.3-7.6 months), and the 1-year survival rate was 29% (95% CI, 22%-38%). In the
      group of patients who underwent curative neurosurgical resection, the overall
      median survival time was 15.2 months (95% CI, 9.2-17.8 months), and the 1-year
      survival rate was 57% (95% CI, 43%-71%). On multivariate analysis, 1 or 2 brain
      metastatic lesions, no extracranial metastatic lesions, and neurosurgical
      resection were independent favorable prognostic factors overall (p = 0.0057,
      0.0197, and <0.0001), and 1 or 2 brain metastatic lesions, no extracranial
      metastatic lesion, and no emergence of secondary brain metastatic lesions were
      independent favorable prognostic factors in the group of patients who underwent
      curative neurosurgical resection (p = 0.0137, 0.0081, and 0.0010). LIMITATIONS:
      This study was limited by its single-institute, retrospective, nonrandomized
      design and selection bias. CONCLUSIONS: Neurosurgical resection in select
      patients is a reasonable option for brain metastasis from colorectal cancer,
      although it is not associated with long-term (5-year) survival. (see Video,
      Supplemental Digital Content 1, http://links.lww.com/DCR/A121 ).

PMID- 24316947
TI  - Systematic review of internet patient information on colorectal cancer surgery.
AB  - BACKGROUND: Patients diagnosed with colorectal cancer often seek information on
      the Internet to help them make treatment decisions. OBJECTIVE: The aim of this
      study is to evaluate the quality of Web-based patient information regarding
      surgery for colorectal cancer. DESIGN: This study is a cross-sectional survey of
      patient-directed Web sites. SETTINGS: The search engine Google (Mountain View,
      CA) and the search terms "colorectal cancer surgery," "colon cancer surgery," and
      "rectal cancer surgery" were used to identify Web sites. MAIN OUTCOME MEASURES:
      To assess quality, we used the DISCERN instrument, a validated questionnaire
      developed to analyze written consumer health information on treatment options to
      aid consumers in evaluating the quality of health-related information on
      treatment choices for a specific health problem. An additional colorectal cancer
      specific questionnaire was used to evaluate Web site content for colorectal
      cancer surgical treatment. Two independent assessors reviewed each Web site.
      RESULTS: Searches revealed a total of 91 distinct Web sites, of which 37 met
      inclusion criteria. Web site affiliation was as follows: 32% open-access general
      information, 24% hospital/health care organization, and 19% professional medical
      society. Twelve (32.4%) Web sites had clear aims, 10 (27.0%) had identifiable
      references to their sources of information, and 9 (24.3%) noted the date of
      published information. Ten sites (27.0%) provided some description of the
      surgical procedure, 8 (21.6%) discussed either the risks or the benefits of
      surgery, and 4 (10.8%) addressed quality-of-life issues. Nineteen (51.4%) Web
      sites discussed postoperative complications, and 7 (18.9%) discussed stoma
      related maintenance/care. LIMITATIONS: The small sample size and interrater
      reliability bias are limitations of this study. CONCLUSIONS: The quality of
      online patient information regarding colorectal cancer treatment is highly
      variable, often incomplete, and does not adequately convey the information
      necessary for patients to make well-informed medical decisions regarding
      treatment for colorectal cancer. An opportunity exists for professional medical
      societies to create more comprehensive online patient information materials that
      may serve as a resource to physicians and their patients (see Video, Supplemental
      Digital Content 1, http://links.lww.com/DCR/A122).

PMID- 24316948
TI  - Impact of the United kingdom national bowel cancer awareness campaign on
      colorectal services.
AB  - BACKGROUND: Poor public awareness may account for the advanced stage at
      diagnosis, hence, poorer survival. With the aim of reducing colorectal cancer
      deaths, the United Kingdom National Bowel Cancer Awareness Campaign was rolled
      out from January 2012. Currently, the United Kingdom government target is to have
      all patients suspected to have cancer seen within 2 weeks of referral from
      general practitioners. This has significant impact on the workload for
      endoscopists. OBJECTIVE: The study aimed to measure the impact on colorectal
      services following the National Bowel Cancer Awareness Campaign. DESIGN: The data
      between February and July 2012 (onset of campaign) were prospectively collected
      and compared with data retrospectively collected between February and July 2011
      inclusive (before campaign). SETTINGS: This study was conducted at a single
      center, university hospital. PATIENTS: The number of 2-week wait referrals,
      investigations, and colorectal cancers detected were assessed. MAIN OUTCOME
      MEASURES: Demographics, staging, and treatment of cancers were compared between
      groups along with the uptake of colorectal cancer screening. RESULTS: The total
      number of 2-week wait referrals increased by 47% with a resultant 38% increase in
      colonic investigations (p = 0.034) and a 23% increase in cancers detected (p =
      0.0157). There was a 6.5% increase in the uptake of screening (p = 0.001) and a
      62.5% decrease in the number of patients with colorectal cancer presenting as an
      emergency. LIMITATIONS: This short period of study is a major limitation.
      Although the data were from prospectively maintained databases, some data were
      analyzed retrospectively. Because only a single unit was assessed, results across
      a wider population may be more pronounced. There was also a referral bias in the
      compliance of primary care in the adherence to the 2-week wait referral criteria,
      because these criteria can be abused to get anxious patients into secondary care
      quickly. CONCLUSIONS: The National Bowel Cancer Awareness Campaign significantly
      increased the demand for colorectal services. With a potentially more favorable
      oncological outcome, further evaluation of supporting this greater workload
      demand is warranted.

PMID- 24316949
TI  - Do clinical characteristics of de novo pouch Crohn's disease after restorative
      proctocolectomy affect ileal pouch retention?
AB  - BACKGROUND: Data on the association between ileal pouch retention and clinical
      characteristics of pouch Crohn's disease developing after restorative
      proctocolectomy for ulcerative colitis are still limited. OBJECTIVE: The aim of
      this study was to identify whether clinical features of pouch Crohn's disease are
      associated with pouch retention. SETTINGS: The study was conducted in a tertiary
      referral center. DESIGN AND PATIENTS: All patients diagnosed with clinically
      active pouch Crohn's disease during follow-up after IPAA for ulcerative colitis
      or indeterminate colitis were identified from an ileal pouch registry. The
      definition of early vs late diagnosis was based on the median time interval to
      diagnosis of Crohn's disease after pouch creation. The associations between pouch
      retention and the clinical features and treatments of pouch Crohn's disease were
      analyzed. OUTCOME MEASURE: The long-term pouch retention rate was estimated by
      using the Kaplan-Meier method. Multivariate logistic regression was used to
      analyze independent factors for pouch failure. RESULTS: From 1993 to 2009, a
      total of 65 (28 males) patients developed de novo pouch Crohn's disease during a
      mean 7.9 years of follow-up after pouch creation. The overall pouch retention
      rate was 57%. The median time from pouch creation to pouch Crohn's disease
      diagnosis was 3.6 years. Univariate analysis demonstrated that early diagnosis of
      pouch Crohn's disease, disease location, and clinical manifestations at the time
      of diagnosis were associated with pouch outcomes, whereas medical therapy or
      perianal surgery was not. Multivariate analysis showed that fistula at the time
      of diagnosis (OR = 17.5, p = 0.002) and early diagnosis (OR = 5.70, p = 0.011)
      were independent risk factors for pouch failure, whereas afferent limb disease
      was associated with pouch retention (OR = 0.07, p = 0.018). LIMITATIONS: The
      retrospective nature of this study and referral bias were limitations.
      CONCLUSIONS: Disease characteristics of de novo pouch Crohn's disease heavily
      influence pouch retention. The interval from pouch construction, fistulizing
      disease, and disease location can be used as prognostic indicators when ileal
      pouch Crohn's disease is diagnosed.

PMID- 24316950
TI  - Infliximab in ulcerative colitis: the impact of preoperative treatment on rates
      of colectomy and prescribing practices in the province of British Columbia,
      Canada.
AB  - BACKGROUND: Approximately 20% of patients with ulcerative colitis will require
      surgical treatment. Recent data suggest that infliximab may reduce the need for
      surgery in patients with severe ulcerative colitis. However, it is unclear
      whether data from these small trials will translate to reduced colectomy rates in
      populations with ulcerative colitis. OBJECTIVE: The purpose of this study was to
      determine the impact of infliximab on the rates of colectomy for ulcerative
      colitis and the prescribing practices for infliximab in British Columbia, Canada.
      DESIGN: We retrospectively reviewed data from 4 province-wide population-based
      databases maintained by the British Columbia Ministry of Health, a central
      registry, a hospital separations file, a physician payment file, and a
      pharmaceutical file. Data were collected from April 1, 2001, to March 31, 2010.
      SETTINGS: This investigation was conducted at the University of British Columbia.
      PATIENTS: All patients aged 18 to 75 with ulcerative colitis were included and
      identified using a validated strategy with International Classification of
      Diseases 9/10 codes. Patients with severe ulcerative colitis were defined by
      treatment with a course of corticosteroids during the study period. Patients
      treated with infliximab were identified using the provincial pharmaceutical file.
      MAIN OUTCOME MEASURES: The primary outcome was surgery determined by an
      International Classification of Diseases 9/10 code for partial or total
      colectomy. RESULTS: Between 2001 and 2010, 7227 subjects were identified with
      ulcerative colitis. The number of subjects with severe ulcerative colitis was
      2537. For general ulcerative colitis, rates of colectomy decreased from 9.97% to
      8.88% in the preinfliximab era (2003-2004) and postinfliximab era (2008-2009; p =
      0.03). For severe ulcerative colitis, there was no significant difference in
      colectomy rates (9.97% vs 11.14%; p = 0.18). The highest rate of infliximab
      prescription was found to be in the provincial health region that encompasses the
      tertiary academic centers of the province. LIMITATIONS: Although the overall
      number of patients in this analysis is sizeable, the number of patients who were
      prescribed infliximab during the study period is relatively modest, which may
      have impacted trends. CONCLUSIONS: In the severe ulcerative colitis population,
      there has been no change in the colectomy rate over time despite the introduction
      of infliximab.

PMID- 24316951
TI  - Reducing urinary tract infections in colon and rectal surgery.
AB  - BACKGROUND: Urinary tract infection is associated with increased morbidity,
      mortality, and healthcare costs. Colon and rectal surgery has been shown to be an
      independent risk factor for urinary tract infection. Decreased length of the
      indwelling urinary catheter may play a role in decreasing the rate of urinary
      tract infection. OBJECTIVE: The aim of this study was to investigate the effect
      of standardized indwelling urinary catheter management on urinary tract
      infection. DESIGN: This was a prospective cohort study. SETTINGS: This study was
      conducted in an urban academic tertiary care center. PATIENTS: All of the
      patients were undergoing colon or rectal resection from 2010 to 2012 at a single
      National Surgical Quality Improvement Program participating institution.
      INTERVENTIONS: Intervention 1 (group 1) included implementation of a daily
      electronic order prompt requiring justification for an indwelling urinary
      catheter for >24 hours. Intervention 2 (group 2) included intervention 1 plus
      sterile intraoperative placement of a urinary catheter after the antiseptic
      preparation and draping of the patient. MAIN OUTCOME MEASURES: The primary
      outcome measured was urinary tract infection rate. RESULTS: A total of 811
      patients were identified (control = 215; group 1 = 476; group 2 = 120). Patient
      demographics and comorbidities were similar among the groups. No differences
      existed in the proportion of proctectomy among the groups. Urinary tract
      infection rate decreased significantly with the implementation of each
      intervention (control, 6.9%; group 1, 2.7%; group 2, 0.8%; p = 0.004). The lone
      urinary tract infection in group 2 involved ureteral reconstruction and stent
      placement at the time of surgery. LIMITATIONS: This study was limited by its
      small sample size and single institution design. CONCLUSIONS: The implementation
      of 2 low-cost practice interventions was associated with a statistically
      significant decrease in urinary tract infection in patients undergoing colorectal
      surgery at an academic tertiary care center.

PMID- 24316952
TI  - Risk factors for readmission after elective colectomy: postoperative
      complications are more important than patient and operative factors.
AB  - BACKGROUND: Colon resections are associated with substantial risk for morbidity
      and readmissions, and these have become markers for quality of care. OBJECTIVE:
      The purpose of this study was to determine risk factors for readmissions after
      elective colectomies to improve patient care and better understand the complex
      issues associated with readmissions. DESIGN: This was an analysis of the
      prospective, statewide, multicenter Michigan Surgical Quality Collaborative
      database. SETTINGS: The analysis was conducted at academic and community medical
      centers in the state of Michigan. PATIENTS: Elective laparoscopic and open
      ileocolic and segmental colectomies from 2008 through 2010 were included. MAIN
      OUTCOME MEASURES: Univariate analysis and a multivariate logistic regression
      model were used to determine influence of patient characteristics, operative
      factors, and postoperative complications on the incidence of 30-day postoperative
      readmission. RESULTS: The readmission rate among 4013 cases was 7.3% (N = 293).
      On the basis of multivariate logistic regression, the top 3 significant risk
      factors associated with readmission were stroke (OR, 10.0 [95% CI, 2.70-37.0]; p
      = 0.001), venous thromboembolism (OR, 6.5 [95% CI, 3.7-11.3]; p < 0.0001), and
      organ-space surgical site infection (OR, 5.6 [95% CI, 3.4-9.4]; p < 0.0001).
      Important factors that contributed to readmission risk but were not found to be
      independent predictors of readmission included diabetes mellitus, preoperative
      steroids, smoking, cardiac comorbidities, age >80 years, anastomotic leaks,
      fascial dehiscence, sepsis, pneumonia, unplanned intubation, and length of stay.
      LIMITATIONS: The Michigan Surgical Quality Collaborative is a large database, and
      true causal relations are difficult to determine; reason for readmission is not
      recorded in the database. CONCLUSIONS: Postoperative complications account for
      the majority of risk factors behind readmissions after elective colectomy,
      whereas preoperative risk factors have less direct influence. Current strategies
      addressing readmission rates should focus on reducing preventable complications.

PMID- 24316953
TI  - Dynamic article: transanal rectal excision: a pilot study.
AB  - BACKGROUND: Laparoscopic total mesorectal excision can be difficult in a narrow
      pelvis. Transanal minimally invasive surgery allows the surgeon to mobilize the
      most distal part of the rectum by using a single port positioned in the anal
      canal. OBJECTIVE: We aim to assess the safety and feasibility of transanal rectal
      excision. DESIGN AND SETTING: This pilot study was conducted in a university
      hospital and tertiary colorectal referral center in Belgium. PATIENTS: Over a 12
      month period, all consecutive patients with benign disease and ASA grade 3
      patients with a rectal carcinoma who required either intersphincteric proctectomy
      or coloanal anastomosis were included. INTERVENTION: After intersphincteric
      dissection or sleeve mucosectomy, a single-access multichannel port was inserted
      into the anal canal. A transanal rectal excision was performed by using
      conventional laparoscopic instruments. The planes were developed as cephalad as
      possible, until the pouch of Douglas was opened. A laparoscopically assisted
      approach was used to gain bowel length and was used in patients who required
      proctectomy. In the case of a reconstruction, a handsewn coloanal anastomosis was
      made. MAIN OUTCOME MEASURES: Intraoperative challenges, conversion rate,
      operating time, blood loss, morbidity, and length of stay were assessed. RESULTS:
      Fourteen patients underwent a transanal rectal excision for both benign (9) and
      malignant (5) disease. In 11 patients (79%), laparoscopically assisted transanal
      minimally invasive rectal excision was performed. The median (range) transanal
      operating time was 55 (35-95) minutes. Intraoperative difficulties hindering
      dissection occurred in 5 patients and were due to inadequate exposure, rectal
      perforation, or fibrosis secondary to radiotherapy for prostate cancer. There was
      minimal postoperative morbidity, with a median follow-up of 6.3 (1.5-13.8)
      months. All patients were discharged within 14 days postoperatively, and there
      were no readmissions. LIMITATIONS: The study was limited by the small number of
      patients. CONCLUSION: Transanal rectal excision is safe and feasible and could be
      a promising technique to facilitate distal rectal mobilization (see Video,
      Supplemental Digital Content 1, http://links.lww.com/DCR/A125).

PMID- 24316954
TI  - Does sedation type affect colonoscopy perforation rates?
AB  - BACKGROUND: Sedation with propofol is gaining popularity. It is unclear whether
      sedation with propofol is associated with colonoscopic perforation. OBJECTIVE:
      The purpose of this study was to compare perforation rates during colonoscopy
      using sedation with or without propofol. DESIGN: This was a retrospective case
      series study. SETTINGS: Data from a tertiary center were analyzed. Demographics,
      method of sedation, and type of endoscopic procedure performed were collected.
      PATIENTS: Patients who underwent a colonoscopy from January 2003 to October 2012
      were analyzed. MAIN OUTCOME MEASURES: Perforation rate expressed per 10,000
      colonoscopies was measured. RESULTS: A total of 118,004 colonoscopies were
      performed during the study period, with 48 perforations (0.041% or 4.1 per
      10,000). Overall, the use of propofol was associated with a 2.5 times increased
      rate of perforation (6.9 vs 2.7 per 10,000; p = 0.0015). Similarly, in patients
      undergoing therapeutic colonoscopies, there was a 3.4-times increased risk of
      perforation associated with the use of propofol (8.7 vs 2.6 per 10,000; p =
      0.0016). However, in patients undergoing diagnostic colonoscopies, there was no
      significantly increased risk of perforation with the use of propofol (4.2 vs 2.9
      per 10,000; p = 0.64). In univariate and multivariate analyses, there were no
      differential perforation risks on the basis of sex, but each decade increase in
      age was associated with an increased risk of perforation. In those patients
      having a therapeutic colonoscopy, age (per decade) and propofol use were
      independently and significantly associated with an increased perforation risk,
      with adjusted ORs of 1.32 (p = 0.04) and 3.38 (p = 0.001). LIMITATIONS: This was
      a retrospective study with the potential for selection bias. CONCLUSIONS: This
      study shows that propofol administration is associated with an increased risk of
      colonoscopic perforation among patients undergoing a therapeutic colonoscopy;
      however, this association was not evident in patients undergoing a diagnostic
      colonoscopy. Further studies, such as a prospective, randomized clinical trial,
      should be done to further evaluate this association.

PMID- 24316955
TI  - A meta-analysis on the effect of sham feeding following colectomy: should gum
      chewing be included in enhanced recovery after surgery protocols?
AB  - BACKGROUND: Sham feeding has been shown to hasten the return of GI function
      following colorectal surgery, before the advent of enhanced recovery after
      surgery protocols. Few data exist regarding the efficacy of sham feeding in the
      modern era, with rapid postoperative feeding. OBJECTIVE: We sought to perform a
      meta-analysis on the effect of sham feeding in colorectal surgery, with a
      separate analysis on trials that used rapid postoperative feeding. DATA SOURCES:
      Cochrane, MEDLINE, EMBASE, Scopus, and PubMed were searched by using the terms
      gum OR sham feeding OR chew AND (colorect OR resect). STUDY SELECTION: All
      studies were randomized controlled trials (in any language) performed on adults,
      comparing standard care with gum chewing following colorectal resection. From 439
      citations, 10 articles were included. INTERVENTION: The intervention was sham
      feeding by means of gum chewing. MAIN OUTCOME MEASURES: The outcome measures were
      time to return of flatus, time to first bowel movement, complication rates,
      length of hospital stay, readmission rates, and reoperation rates. RESULTS: Ten
      randomized controlled trials (n = 612) were included. Sham feeding resulted in a
      reduction in time to flatus of 31 minutes (p = 0.003) and time to first bowel
      movement of 30 minutes (p = 0.05). Sham feeding also resulted in a reduction in
      length of stay by 0.5 days (p = 0.007), and a reduction in complication rates
      (relative risk = 0.687, p = 0.017), although this appeared to be associated with
      publication bias. Analysis of trials that used rapid postoperative feeding (n =
      282) revealed no difference in postoperative GI function. LIMITATIONS: This
      review was limited by the heterogeneity of postoperative feeding regimes, in
      addition to limited reporting by trials of postoperative morbidity. CONCLUSIONS:
      Sham feeding following colorectal surgery is safe, results in small improvements
      in GI recovery, and is associated with a reduction in the length of hospital
      stay. It confers no advantage if patients are placed on a rapid postoperative
      feeding regime.

PMID- 24316956
TI  - Lymph node status does not predict local recurrence in the total mesorectal
      excision era.

PMID- 24316957
TI  - Perfect treatment in an imperfect world: surgery alone or radiation for node
      positive rectal cancer?

PMID- 24316958
TI  - Bilateral puborectalis interposition repair of rectourethral fistula.
AB  - BACKGROUND: Rectourethral fistula is a rare but significant complication that
      often requires operative intervention. OBJECTIVE: A new perineal approach using
      the medial aspect of the puborectalis muscles as a double-breasted rotational
      interposition flap to repair the rectourethral fistula is hereby described.
      PROCEDURE: With the patient in a modified Lloyd-Davies position, a vertical
      midline incision from the base of the scrotum to 2 cm anterior to the anal verge
      is made. The dissection continues along the anterior rectal wall through the
      Denonvilliers fascia until the rectourethral fistula is reached. The dissection
      through the fused Denonvilliers fascia continues a further 1 to 2 cm above the
      fistula. The openings in the rectum and the urethra are then closed vertically
      (urethra) and horizontally (rectum) with interrupted 3/0 and 4/0 polyglactin
      sutures. The puborectalis muscles are then mobilized as a 1-cm strip bilaterally
      and released posteriorly at the level of the anorectum. The 2 strips of the
      puborectalis muscles are then rotated medially and superiorly along its anterior
      attachments, forming a double -breasted overlapping flap overlying the fistula
      openings. The flaps are anchored into the superior and contralateral aspect of
      the surgical field with the use of 2/0 polyglactin sutures. RESULTS: From
      November 2011 to December 2012, 4 patients underwent this procedure. No
      perioperative complications, including those related to the harvesting of the
      puborectalis muscles, were identified. Subsequent radiological studies confirmed
      the success of the procedure. After a median follow-up of 8 (6-18) months, 3
      patients had their colostomy reversed and remained continent, whereas the last
      patient had a permanent ileostomy. None of the patients reported any urinary
      leakage through the perineum. CONCLUSIONS: The double-breasted puborectalis
      interposition flap is an alternative transperineal procedure in the management of
      rectourethral fistula. It avoids a laparotomy and is rectum sparing.

PMID- 24316959
TI  - Repeat intestinal resections increase the risk of recurrence of Crohn's disease:
      is there more than meets the eye?

PMID- 24316960
TI  - Author reply: To PMID 23739195.

PMID- 24316963
TI  - Self-assessment quiz: answers, critiques, and references.

PMID- 24316964
TI  - Evaluation of the economic burden of diseases associated with poor nutrition
      status.
AB  - BACKGROUND: Geriatric acutely ill patients may frequently have insufficient
      nutrition intake, leading to malnutrition and increased susceptibility to
      additional morbidity. This compromised health status can increase costs by
      extending length of stay in the hospital, promoting the development of
      comorbidities, and requiring more intensive care. Understanding the value of
      measures improving the health of these patients depends in part on estimating the
      costs of prevented adverse outcomes. Because clinical trials often do not record
      these costs, it is difficult to assess the value of nutrition interventions.
      MATERIALS AND METHODS: This article comprehensively reviews 15 years of clinical
      trials of nutrition interventions to identify salient diseases and complications
      measured by previous clinical trials and then estimates costs corresponding with
      these conditions associated with poor nutrition status. RESULTS: The most costly
      complication associated with poor nutrition status is acute respiratory
      infections ($13,350-$19,530 per hospitalization), while institutional long-term
      care is the greatest chronic cost contributor across many diseases ($77,000 per
      year of care). CONCLUSION: This review can facilitate imputation of nutrition
      intervention benefits for acutely ill patients by characterizing the costs of
      clinical outcomes often reported in trials.

PMID- 24316965
TI  - Simulation in developing countries.

PMID- 24316966
TI  - In reply: simulation in developing countries.

PMID- 24316967
TI  - Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell
      lung cancer (NSCLC) patients: a case series study on 15 patients.
AB  - BACKGROUND: The combination of paclitaxel and bevacizumab was EMA-approved as
      first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed
      a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab.
      METHODS: Between November 2008 and March 2010, this case series study included 15
      patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were
      bevacizumab eligible and received the same regimen used in metastatic breast
      cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10
      mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy
      was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial
      progenitor cells (CEP) and circulating endothelial cells (CEC) levels were
      explored in a subset of patients. RESULTS: Median age 56 (36-75), female: 47%,
      never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients
      were treated with a first-line platinum-based doublet with or without bevacizumab
      and 70% of them with erlotinib in the second-line. No major toxicity was
      observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT
      scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median
      progression free survival was 4.6 months. An increase of CEC and CEP was observed
      in patients with NSCLC treated with paclitaxel and bevacizumab. CONCLUSION: In
      this retrospective series, our results suggest efficacy signal in pre-treated
      metastatic NSCLC and warrant further assessment in a randomized clinical trial.

PMID- 24316968
TI  - Carnosol inhibits cell adhesion molecules and chemokine expression by tumor
      necrosis factor-alpha in human umbilical vein endothelial cells through the
      nuclear factor-kappaB and mitogen-activated protein kinase pathways.
AB  - Inflammatory bowel diseases (IBD) are gastrointestinal disorders associated with
      chronic inflammatory processes. Carnosol has been demonstrated to possess anti
      inflammatory properties. This study examined the suppressive effect of carnosol
      on the expression of cell adhesion molecules (CAMs) and chemokines in human
      umbilical vein endothelial cells (HUVECs) and the possible underlying mechanism.
      The effect of carnosol on CAM and chemokine expression in HUVECs was identified
      by western blotting and ELISA, respectively. nuclear factor (NF)-kappaB
      activation of HUVECs was analyzed using the TransAM NF-kappaB Family kit. The
      effect of carnosol on the tumor necrosis factor (TNF)-alpha-induced activation of
      the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways, and was
      subsequently analyzed using western blotting. Carnosol not only inhibited TNF
      alpha-induced protein expression of intercellular adhesion molecule (ICAM)-1,
      vascular cell adhesion molecule (VCAM)-1 and E-selectin in HUVECs, but also
      suppressed interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1
      expression. In addition, carnosol inhibited the TNF-alpha-induced phosphorylation
      of p-65 and IkappaB-alpha, as well as the activation of NF-kappaB. The same
      result was observed in TNF-alpha-stimulated phosphorylation of ERK1/2 and p-38.
      It was demonstrated that carnosol inhibited TNF-alpha-induced CAM and chemokine
      expression in HUVECs. The underlying mechanism may be associated with the
      blocking of the NF-kappaB and MAPK pathways. These results indicate that carnosol
      may be a novel therapeutic agent for targeting endothelial cells in IBDs.

PMID- 24316969
TI  - Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways.
AB  - There is a considerable resurgence of interest in the role of aerobic glycolysis
      in cancer; however, increased glycolysis is frequently viewed as a consequence of
      oncogenic events that drive malignant cell growth and survival. Here we provide
      evidence that increased glycolytic activation itself can be an oncogenic event in
      a physiologically relevant 3D culture model. Overexpression of glucose
      transporter type 3 (GLUT3) in nonmalignant human breast cells activated known
      oncogenic signaling pathways, including EGFR, beta1 integrin, MEK, and AKT,
      leading to loss of tissue polarity and increased growth. Conversely, reduction of
      glucose uptake in malignant cells promoted the formation of organized and growth
      arrested structures with basal polarity, and suppressed oncogenic pathways.
      Unexpectedly and importantly, we found that unlike reported literature, in 3D the
      differences between "normal" and malignant phenotypes could not be explained by
      HIF-1alpha/2alpha, AMPK, or mTOR pathways. Loss of epithelial integrity involved
      activation of RAP1 via exchange protein directly activated by cAMP (EPAC),
      involving also O-linked N-acetylglucosamine modification downstream of the
      hexosamine biosynthetic pathway. The former, in turn, was mediated by pyruvate
      kinase M2 (PKM2) interaction with soluble adenylyl cyclase. Our findings show
      that increased glucose uptake activates known oncogenic pathways to induce
      malignant phenotype, and provide possible targets for diagnosis and therapeutics.

PMID- 24316970
TI  - Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3
      degradation.
AB  - The cytokines RANKL and TNF activate NF-kappaB signaling in osteoclast precursors
      (OCPs) to induce osteoclast (OC) formation. Conversely, TNF can limit OC
      formation through NF-kappaB p100, which acts as an inhibitor, and TNF receptor
      associated receptor 3 (TRAF3); however, a role for TRAF3 in RANKL-mediated OC
      formation is unknown. We found that TRAF3 limits RANKL-induced osteoclastogenesis
      by suppressing canonical and noncanonical NF-kappaB signaling. Conditional OC
      specific Traf3-KO (cKO) mice had mild osteoporosis and increased OC formation.
      RANKL induced TRAF3 degradation via the lysosome/autophagy system. The
      autophagy/lysosome inhibitor chloroquine reduced RANKL-induced OC formation and
      function by increasing TRAF3 expression in OCPs in vitro and in vivo. Although
      chloroquine had no effect on basal bone resorption, it inhibited parathyroid
      hormone- and ovariectomy-induced OC activation in WT, but not cKO, mice. Deletion
      of the transcription factor gene Relb resulted in increased TRAF3 expression in
      OCPs, which was associated with decreased RANKL-induced TRAF3 degradation. RelB
      directly increased expression of BECN1, a key autophagy regulator, by binding to
      its promoter. These data indicate that autophagic/lysosomal degradation of TRAF3
      is an important step in RANKL-induced NF-kappaB activation in OCPs. Furthermore,
      treatments that increase TRAF3 levels in OCPs, including pharmacological
      inhibition of its degradation with compounds such as chloroquine, may limit bone
      destruction in common bone diseases. 

PMID- 24316971
TI  - Hematopoietic stem cells are acutely sensitive to Acd shelterin gene
      inactivation.
AB  - The shelterin complex plays dual functions in telomere homeostasis by recruiting
      telomerase and preventing the activation of a DNA damage response at telomeric
      ends. Somatic stem cells require telomerase activity, as evidenced by progressive
      stem cell loss leading to bone marrow failure in hereditary dyskeratosis
      congenita. Recent work demonstrates that dyskeratosis congenita can also arise
      from mutations in specific shelterin genes, although little is known about
      shelterin functions in somatic stem cells. We found that mouse hematopoietic stem
      cells (HSCs) are acutely sensitive to inactivation of the shelterin gene Acd,
      encoding TPP1. Homozygosity for a hypomorphic acd allele preserved the emergence
      and expansion of fetal HSCs but led to profoundly defective function in
      transplantation assays. Upon complete Acd inactivation, HSCs expressed p53 target
      genes, underwent cell cycle arrest, and were severely depleted within days,
      leading to hematopoietic failure. TPP1 loss induced increased telomeric fusion
      events in bone marrow progenitors. However, unlike in epidermal stem cells, p53
      deficiency did not rescue TPP1-deficient HSCs, indicating that shelterin
      dysfunction has unique effects in different stem cell populations. Because the
      consequences of telomere shortening are progressive and unsynchronized, acute
      loss of shelterin function represents an attractive alternative for studying
      telomere crisis in hematopoietic progenitors. 

PMID- 24316972
TI  - Embryonic exposure to excess thyroid hormone causes thyrotrope cell death.
AB  - Central congenital hypothyroidism (CCH) is more prevalent in children born to
      women with hyperthyroidism during pregnancy, suggesting a role for thyroid
      hormone (TH) in the development of central thyroid regulation. Using the
      zebrafish embryo as a model for thyroid axis development, we have characterized
      the ontogeny of negative feedback regulation of thyrotrope function and examined
      the effect of excess TH on thyrotrope development. We found that thyroid
      stimulating hormone beta subunit (tshb) and type 2 deiodinase (dio2) are
      coexpressed in zebrafish thyrotropes by 48 hours after fertilization and that TH
      driven negative feedback regulation of tshb transcription appears in the thyroid
      axis by 96 hours after fertilization. Negative feedback regulation correlated
      with increased systemic TH levels from the developing thyroid follicles. We used
      a transgenic zebrafish that expresses GFP under the control of the tshb promoter
      to follow thyrotrope fates in vivo. Time-lapse imaging revealed that early
      exposure to elevated TH leads to thyrotrope cell death. Thyrotrope numbers slowly
      recovered following the removal of excess TH. These data demonstrate that
      transient TH exposure profoundly impacts the thyrotrope population during a
      critical period of pituitary development and may have long-term implications for
      the functional reserve of thyroid-stimulating hormone (TSH) production and the
      TSH set point later in life. 

PMID- 24316973
TI  - Diverting T helper cell trafficking through increased plasticity attenuates
      autoimmune encephalomyelitis.
AB  - Naive T helper cells differentiate into functionally distinct effector subsets
      that drive specialized immune responses. Recent studies indicate that some of the
      effector subsets have plasticity. Here, we used an EAE model and found that Th17
      cells deficient in the transcription factor BCL11B upregulated the Th2-associated
      proteins GATA3 and IL-4 without decreasing RAR-related orphan receptor gamma
      (RORgammat), IL-17, and GM-CSF levels. Surprisingly, abnormal IL-4 production
      affected Th17 cell trafficking, diverting migration from the draining lymph
      nodes/CNS route to the mesenteric lymph nodes/gut route, which ameliorated EAE
      without overt colitis. T helper cell rerouting in EAE was dependent on IL-4,
      which enhanced retinoic acid (RA) production by dendritic cells, which further
      induced expression of gut-homing receptors CCR9 and alpha4beta7 on Bcl11b
      deficient CD4+ T cells. Furthermore, IL-4 treatment or Th2 immunization of wild
      type mice with EAE caused no alteration in Th17 cytokines or RORgammat, but
      diverted T helper cell trafficking to the gut, which improved EAE outcome without
      overt colitis. Our data demonstrate that Th17 cells are permissive to Th2 gene
      expression without affecting Th17 gene expression. This Th17 plasticity has an
      impact on trafficking, which is a critical component of the immune response and
      may represent a possible avenue for treating multiple sclerosis. 

PMID- 24316974
TI  - Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells.
AB  - Breast cancer (BC) can recur as metastatic disease many years after primary tumor
      removal, suggesting that disseminated tumor cells survive for extended periods in
      a dormant state that is refractory to conventional therapies. We have previously
      shown that altering the tumor microenvironment through fibrosis with collagen and
      fibronectin deposition can trigger tumor cells to switch from a dormant to a
      proliferative state. Here, we used an in vivo preclinical model and a 3D in vitro
      model of dormancy to evaluate the role of Src family kinase (SFK) in regulating
      this dormant-to-proliferative switch. We found that pharmacological inhibition of
      SFK signaling or Src knockdown results in the nuclear localization of cyclin
      dependent kinase inhibitor p27 and prevents the proliferative outbreak of dormant
      BC cells and metastatic lesion formation; however, SFK inhibition did not kill
      dormant cells. Dormant cell proliferation also required ERK1/2 activation.
      Combination treatment of cells undergoing the dormant-to-proliferative switch
      with the Src inhibitor (AZD0530) and MEK1/2 inhibitor (AZD6244) induced apoptosis
      in a large fraction of the dormant cells and delayed metastatic outgrowth,
      neither of which was observed with either inhibitor alone. Thus, targeting Src
      prevents the proliferative response of dormant cells to external stimuli, but
      requires MEK1/2 inhibition to suppress their survival. These data indicate that
      treatments targeting Src in combination with MEK1/2 may prevent BC recurrence. 

PMID- 24316977
TI  - Cardiologists urged to reduce inappropriate radiation exposure.

PMID- 24316975
TI  - MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer
      prognosis.
AB  - Metabolic profiling of cancer cells has recently been established as a promising
      tool for the development of therapies and identification of cancer biomarkers.
      Here we characterized the metabolomic profile of human breast tumors and
      uncovered intrinsic metabolite signatures in these tumors using an untargeted
      discovery approach and validation of key metabolites. The oncometabolite 2
      hydroxyglutarate (2HG) accumulated at high levels in a subset of tumors and human
      breast cancer cell lines. We discovered an association between increased 2HG
      levels and MYC pathway activation in breast cancer, and further corroborated this
      relationship using MYC overexpression and knockdown in human mammary epithelial
      and breast cancer cells. Further analyses revealed globally increased DNA
      methylation in 2HG-high tumors and identified a tumor subtype with high tissue
      2HG and a distinct DNA methylation pattern that was associated with poor
      prognosis and occurred with higher frequency in African-American patients. Tumors
      of this subtype had a stem cell-like transcriptional signature and tended to
      overexpress glutaminase, suggestive of a functional relationship between
      glutamine and 2HG metabolism in breast cancer. Accordingly, 13C-labeled glutamine
      was incorporated into 2HG in cells with aberrant 2HG accumulation, whereas
      pharmacologic and siRNA-mediated glutaminase inhibition reduced 2HG levels. Our
      findings implicate 2HG as a candidate breast cancer oncometabolite associated
      with MYC activation and poor prognosis. 

PMID- 24316978
TI  - Two new bismuth thiourea bromides: crystal structure, growth, and
      characterization.
AB  - Crystals of two new bismuth thiourea bromides, bismuth trithiourea bromide
      (Bi[CS(NH2)2]3Br3, BTB) and bismuth protonated-hexathiourea bromide
      (Bi[CS(NH2)2H]6Br9, BHB), have been successfully grown from hydrobromic acid
      solution with different pH values by slow evaporation. Single crystal X-ray
      diffraction reveals that BTB is isostructural to its Cl-analog crystallizing in a
      monoclinic space group Cc with unit cell dimensions of a = 8.6238(7) A, b =
      12.2506(11) A, c = 15.5040(13) A, beta = 90.7810(10) degrees  and Z = 4. In
      contrast, BHB crystallizes in a trigonal space group R3[combining macron]c with
      unit cell dimensions of a = b = 12.748(17) A, c = 40.45(11) A, and Z = 6. The
      protonation of the thiourea in BHB is confirmed by the structure solution, IR and
      Raman spectroscopy. The UV diffuse reflection spectra clearly indicate that both
      of the two crystals have good optical transparency in the range below 2000 nm.
      Both compounds decompose above 190  degrees C, and BHB melts at around 140 
      degrees C while BTB possesses a phase transition at 145  degrees C as indicated
      by thermogravimetric (TG) and differential thermal analysis (DTA). 

PMID- 24316976
TI  - LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis.
AB  - Corneal integrity and transparency are indispensable for good vision. Cornea
      homeostasis is entirely dependent upon corneal stem cells, which are required for
      complex wound-healing processes that restore corneal integrity following
      epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin
      like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal
      epithelial stem cell population and sporadically expressed in the basal cells of
      ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial
      cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell
      recruitment following injury and promoted a cell-fate switch from transparent
      epithelium to keratinized skin-like epidermis, which led to corneal blindness. In
      addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent
      inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1-/- mice rescued
      pathological phenotypes and prevented corneal opacity. Additionally, transgenic
      mice that expressed a constitutively active form of STAT3 in the corneal
      epithelium had abnormal features, including corneal plaques and
      neovascularization similar to that found in Lrig1-/- mice. Bone marrow chimera
      experiments indicated that LRIG1 also coordinates the function of bone marrow
      derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates
      corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a
      key regulator of tissue homeostasis. 

PMID- 24316979
TI  - Inactivating CUX1 mutations promote tumorigenesis.
AB  - A major challenge in cancer genetics is to determine which low-frequency somatic
      mutations are drivers of tumorigenesis. Here we interrogate the genomes of 7,651
      diverse human cancers and find inactivating mutations in the homeodomain
      transcription factor gene CUX1 (cut-like homeobox 1) in ~1-5% of various tumors.
      Meta-analysis of CUX1 mutational status in 2,519 cases of myeloid malignancies
      reveals disruptive mutations associated with poor survival, highlighting the
      clinical significance of CUX1 loss. In parallel, we validate CUX1 as a bona fide
      tumor suppressor using mouse transposon-mediated insertional mutagenesis and
      Drosophila cancer models. We demonstrate that CUX1 deficiency activates
      phosphoinositide 3-kinase (PI3K) signaling through direct transcriptional
      downregulation of the PI3K inhibitor PIK3IP1 (phosphoinositide-3-kinase
      interacting protein 1), leading to increased tumor growth and susceptibility to
      PI3K-AKT inhibition. Thus, our complementary approaches identify CUX1 as a pan
      driver of tumorigenesis and uncover a potential strategy for treating CUX1-mutant
      tumors.

PMID- 24316980
TI  - Genetic variation of a bacterial pathogen within individuals with cystic fibrosis
      provides a record of selective pressures.
AB  - Advances in sequencing technologies have enabled the identification of mutations
      acquired by bacterial pathogens during infection. However, it remains unclear
      whether adaptive mutations fix in the population or lead to pathogen
      diversification within the patient. Here we study the genotypic diversity of
      Burkholderia dolosa within individuals with cystic fibrosis by resequencing
      individual colonies and whole populations from single sputum samples. We find
      extensive intrasample diversity, suggesting that mutations rarely fix in a
      patient's pathogen population--instead, diversifying lineages coexist for many
      years. Under strong selection, multiple adaptive mutations arise, but none of
      these sweep to fixation, generating lasting allele diversity that provides a
      recorded signature of past selection. Genes involved in outer-membrane
      components, iron scavenging and antibiotic resistance all showed this signature
      of within-patient selection. These results offer a general and rapid approach for
      identifying the selective pressures acting on a pathogen in individual patients
      based on single clinical samples.

PMID- 24316983
TI  - Decision-making deficit of a patient with axonal damage after traumatic brain
      injury.
AB  - Patients with traumatic brain injury (TBI) were reported to have difficulty
      making advantageous decisions, but the underlying deficits of the network of
      brain areas involved in this process were not directly examined. We report a
      patient with TBI who demonstrated problematic behavior in situations of risk and
      complexity after cerebral injury from a traffic accident. The Iowa gambling task
      (IGT) was used to reveal his deficits in the decision-making process. To examine
      underlying deficits of the network of brain areas, we examined T1-weighted
      structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient.
      The patient showed abnormality in IGT. DTI-MRI results showed a significant
      decrease in fractional anisotropy (FA) in the fasciculus between the brain stem
      and cortical regions via the thalamus. He showed significant decrease in gray
      matter volumes in the bilateral insular cortex, hypothalamus, and posterior
      cingulate cortex, possibly reflecting Wallerian degeneration secondary to the
      fasciculus abnormalities. SPECT showed significant blood flow decrease in the
      broad cortical areas including the ventromedial prefrontal cortex (VM). Our study
      showed that the patient had dysfunctional decision-making process.
      Microstructural abnormality in the fasciculus, likely from the traffic accident,
      caused reduced afferent feedback to the brain, resulting in less efficient
      decision-making. Our findings support the somatic-marker hypothesis (SMH), where
      somatic feedback to the brain influences the decision-making process. 

PMID- 24316981
TI  - Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain
      specific DNMT3B isoform in the embryonal brain tumor ETMR.
AB  - Embryonal tumors with multilayered rosettes (ETMRs) are rare, deadly pediatric
      brain tumors characterized by high-level amplification of the microRNA cluster
      C19MC. We performed integrated genetic and epigenetic analyses of 12 ETMR samples
      and identified, in all cases, C19MC fusions to TTYH1 driving expression of the
      microRNAs. ETMR tumors, cell lines and xenografts showed a specific DNA
      methylation pattern distinct from those of other tumors and normal tissues. We
      detected extreme overexpression of a previously uncharacterized isoform of DNMT3B
      originating at an alternative promoter that is active only in the first weeks of
      neural tube development. Transcriptional and immunohistochemical analyses suggest
      that C19MC-dependent DNMT3B deregulation is mediated by RBL2, a known repressor
      of DNMT3B. Transfection with individual C19MC microRNAs resulted in DNMT3B
      upregulation and RBL2 downregulation in cultured cells. Our data suggest a
      potential oncogenic re-engagement of an early developmental program in ETMR via
      epigenetic alteration mediated by an embryonic, brain-specific DNMT3B isoform. 

PMID- 24316982
TI  - Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a
      chronic hepatitis B mouse model.
AB  - The most common risk factor for developing hepatocellular carcinoma (HCC) is
      chronic infection with hepatitis B virus (HBV). To better understand the
      evolutionary forces driving HCC, we performed a near-saturating transposon
      mutagenesis screen in a mouse HBV model of HCC. This screen identified 21
      candidate early stage drivers and a very large number (2,860) of candidate later
      stage drivers that were enriched for genes that are mutated, deregulated or
      functioning in signaling pathways important for human HCC, with a striking 1,199
      genes being linked to cellular metabolic processes. Our study provides a
      comprehensive overview of the genetic landscape of HCC. 

PMID- 24316984
TI  - Effects of intraluminal thrombus on patient-specific abdominal aortic aneurysm
      hemodynamics via stereoscopic particle image velocity and computational fluid
      dynamics modeling.
AB  - The pathology of the human abdominal aortic aneurysm (AAA) and its relationship
      to the later complication of intraluminal thrombus (ILT) formation remains
      unclear. The hemodynamics in the diseased abdominal aorta are hypothesized to be
      a key contributor to the formation and growth of ILT. The objective of this
      investigation is to establish a reliable 3D flow visualization method with
      corresponding validation tests with high confidence in order to provide insight
      into the basic hemodynamic features for a better understanding of hemodynamics in
      AAA pathology and seek potential treatment for AAA diseases. A stereoscopic
      particle image velocity (PIV) experiment was conducted using transparent patient
      specific experimental AAA models (with and without ILT) at three axial planes.
      Results show that before ILT formation, a 3D vortex was generated in the AAA
      phantom. This geometry-related vortex was not observed after the formation of
      ILT, indicating its possible role in the subsequent appearance of ILT in this
      patient. It may indicate that a longer residence time of recirculated blood flow
      in the aortic lumen due to this vortex caused sufficient shear-induced platelet
      activation to develop ILT and maintain uniform flow conditions. Additionally, two
      computational fluid dynamics (CFD) modeling codes (Fluent and an in-house
      cardiovascular CFD code) were compared with the two-dimensional, three-component
      velocity stereoscopic PIV data. Results showed that correlation coefficients of
      the out-of-plane velocity data between PIV and both CFD methods are greater than
      0.85, demonstrating good quantitative agreement. The stereoscopic PIV study can
      be utilized as test case templates for ongoing efforts in cardiovascular CFD
      solver development. Likewise, it is envisaged that the patient-specific data may
      provide a benchmark for further studying hemodynamics of actual AAA, ILT, and
      their convolution effects under physiological conditions for clinical
      applications. 

PMID- 24316987
TI  - Obesity revisited, yet again.

PMID- 24316988
TI  - The Canterbury Charity Hospital: facing the challenge of unmet need in
      healthcare.

PMID- 24316985
TI  - Post-translational modifications of the histone variant H2AZ.

PMID- 24316986
TI  - Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon
      receptor expression in murine embryonic stem cells.
AB  - The aryl hydrocarbon receptor (AHR) is a transcription factor and environmental
      sensor that regulates expression of genes involved in drug-metabolism and cell
      cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice
      and studies with orthologous genes in invertebrates suggest that AHR may also
      play a significant role in embryonic development. To address this hypothesis, we
      studied the regulation of Ahr expression in mouse embryonic stem cells and their
      differentiated progeny. In ES cells, interactions between OCT3/4, NANOG, SOX2 and
      Polycomb Group proteins at the Ahr promoter repress AHR expression, which can
      also be repressed by ectopic expression of reprogramming factors in hepatoma
      cells. In ES cells, unproductive RNA polymerase II binds at the Ahr transcription
      start site and drives the synthesis of short abortive transcripts. Activation of
      Ahr expression during differentiation follows from reversal of repressive marks
      in Ahr promoter chromatin, release of pluripotency factors and PcG proteins,
      binding of Sp factors, establishment of histone marks of open chromatin, and
      engagement of active RNAPII to drive full-length RNA transcript elongation. Our
      results suggest that reversible Ahr repression in ES cells holds the gene poised
      for expression and allows for a quick switch to activation during embryonic
      development. 

PMID- 24316989
TI  - A nationwide survey of weight control practices among middle-aged New Zealand
      women.
AB  - AIM: To examine the prevalence of weight control practices in a nationwide
      representative sample of 40-50 year old New Zealand women. METHODS: In May 2009,
      a cross-sectional mail survey was conducted among 2500 women randomly selected
      from nationwide electoral rolls who were each mailed a self-administered
      questionnaire about their weight control practices, demographics and
      anthropometry. RESULTS: After excluding ineligible recipients, a 66%
      participation rate was achieved (n=1601). Thirty-nine percent of the sample
      (n=630) reported trying to control their weight, and among those who were not,
      69% (n=674) were attempting to prevent weight gain. The weight control practices
      most commonly used were cutting down on meal/snack size (42%) and cutting down on
      fats/sugars (45%). Smoking, exercising in a driven or compulsive way, and fasting
      were used at least once a week as weight control strategies by 14%, 22% and 5% of
      women, respectively. Other potentially health-damaging practices (i.e. laxatives,
      diuretics, diet pills, vomiting) were employed by 1-4% of women. CONCLUSIONS:
      Most women reported weight control practices that were consistent with public
      health messages, however the use of smoking and exercising in a driven or
      compulsive way are of particular concern.

PMID- 24316990
TI  - Long-term outcomes in gastric bypass patients with and without type 2 diabetes-
      Waitemata District Health Board experience.
AB  - BACKGROUND/OBJECTIVES: Dramatic early postoperative improvement or resolution of
      type 2 diabetes mellitus (T2DM) has been widely reported after bariatric surgery
      but there is limited long-term data on T2DM outcome. Moreover, data on long-term
      weight outcomes of government funded bariatric surgery in New Zealand is lacking.
      We report weight and glycaemic outcomes in subjects with and without T2DM who
      underwent gastric bypass surgery (GBP) at Waitemata District Health Board (WDHB).
      METHODS: Clinical records of those who underwent a GBP (Roux-en-Y gastric bypass
      or loop gastric bypass) at WDHB between 2001 and 2007 were reviewed. Relevant pre
      and postoperative data, including weight and diabetes related parameters, were
      collected from hospital records and analysed. Missing clinical data was attained
      by contacting patients, their primary practitioners and local laboratories, and
      also by performing HbA1c in T2DM subjects in whom latest diabetes status was
      unclear. RESULTS: Data of 126 subjects was analysed. Their mean age was 43.7
      years, 73% were female and 83% were Pakeha/European. Mean preoperative weight was
      136.2 kg (SD plus or minus 29.1, range 81.3-241) with a mean BMI of 48.3 kg/m2.
      Postoperative nadir weight was 80.6 kg (SD plus or minus 18.1, range 48.0-132.8)
      at 20.8 months (SD plus or minus 14.6, range 4-98) (BMI 28.6) with percentage of
      excess body weight loss (%EBWL) of 84.7%. Latest mean weight was 90.5 kg (SD plus
      or minus 18.8, range 57-140) (BMI 32.2, %EBWL 70.7%) at a mean of 63.4 months (SD
      plus or minus 19.7, range 12-109) post-op. Thirty four subjects (27.0%) had
      preoperative diagnosis of T2DM, of whom 29 (85.3%) had complete remission at some
      stage postoperatively. At the latest follow-up, 19 of 33 (57.6%) remained in
      complete remission, and the rest had either never remitted or had evidence of
      T2DM relapse after an initial remission. Weight loss outcomes were comparable
      between T2DM and non-T2DM subjects, and also between European and Maori and
      Pacific Islanders. CONCLUSION: GBP resulted in substantial weight loss in
      essentially all subjects, and weight loss was well maintained over time. GBP also
      had dramatic and favourable effect on T2DM but did not uniformly result in
      prolonged diabetes remission. Long-term glycaemic surveillance is desirable.

PMID- 24316991
TI  - The Canterbury Charity Hospital: an update (2010-2012) and effects of the
      earthquakes.
AB  - AIM: To update activities of the Canterbury Charity Hospital (CCH) and its Trust
      over the 3 years 2010-2012, during which the devastating Christchurch earthquakes
      occurred. METHODS: Patients' treatments, establishment of new services, expansion
      of the CCH, staffing and finances were reviewed. RESULTS: Previously established
      services including general surgery continued as before, some services such as
      ophthalmology declined, and new services were established including colonoscopy,
      dentistry and some gynaecological procedures; counselling was provided following
      the earthquakes. Teaching and research endeavours increased. An adjacent property
      was purchased and renovated to accommodate the expansion. The Trust became
      financially self-sustaining in 2010; annual running costs of $340,000/year were
      maintained but were anticipated to increase soon. Of the money generously donated
      by the community to the Trust, 82% went directly to patient care. Although not
      formally recorded, hundreds of appointment request were rejected because of
      service unavailability or unmet referral criteria. CONCLUSIONS: This 3-year
      review highlights substantial, undocumented unmet healthcare needs in the region,
      which were exacerbated by the 2010/2011 earthquakes. We contend that the level of
      unmet healthcare in Canterbury and throughout the country should be regularly
      documented to inform planning of public healthcare services.

PMID- 24316992
TI  - Patient-reported outcomes following breast reconstruction surgery in a public
      hospital: use of the Breast-Q questionnaire.
AB  - AIM: To assess patients' quality of life and satisfaction with individual
      outcomes following breast reconstructive surgery, using the BREAST-Q
      questionnaire. METHODS: The BREAST-Q questionnaire was used to collect
      information on patients' satisfaction in various domains following breast
      reconstructive surgery. The questionnaire answers were entered into the Qscore
      Excel template. Scores for each domain were obtained and different comparison
      groups were analysed for statistical significance. RESULTS: Overall, patients
      showed above average satisfaction in majority of the domains. No statistically
      significant difference in satisfaction was seen with breast or overall outcome
      when compared by type or timing of reconstruction; presence or absence of
      significant complication; and completed or ongoing surgery. However, some
      difference in satisfaction with medical and office staff by ethnicity was
      evident, with Europeans being more satisfied than Maori or other ethnicities.
      CONCLUSION: The BREAST-Q questionnaire is a valuable tool to provide patient
      satisfaction information on breast reconstruction. Our retrospective audit shows
      that our patients are currently satisfied with their breast and outcomes overall.
      We will now use this tool prospectively to assess our patients' progress and
      satisfaction, and improve our service delivery for our future patients.

PMID- 24316993
TI  - Lack of relationship between obesity and mortality or morbidity after coronary
      artery bypass grafting.
AB  - AIMS: Obesity has significant adverse effects on cardiovascular health.
      Conflicting results have been reported regarding relationships between body mass
      index (BMI) and outcomes after coronary artery bypass grafting (CABG). We
      compared outcomes of CABG patients by BMI categories. METHODS: Isolated CABG
      performed between July 2010-June 2012 at Auckland City Hospital were categorised
      into four groups of BMI <=25 (normal), >25-30 (overweight), >30-35 (obese) and
      >35 kg/m2 (morbidly obese) retrospectively for analyses. RESULTS: The four groups
      had 181(22.4%), 320 (39.6%), 205 (25.3%) and 103 (12.7%) patients respectively.
      Increasing BMI was associated with younger age (p<0.001) and increasing
      creatinine clearance (p<0.001). Obesity was associated with a higher proportion
      of patients of Maori or Pacific ethnicity and patients with more hypertension.
      Morbid obesity was associated with female sex, higher mean New Zealand
      Deprivation Index, diabetes, longer operation time and sternal wound infection.
      Thirty-day mortality (p=0.702), composite morbidity (p=0.904) and survival
      (p=0.112) during 1.4 +/- 0.6 years of follow-up were similar across BMI
      categories. CONCLUSION: Obesity was common and was present in over a third of
      patients undergoing CABG with 13% of the entire cohort being morbidly obese.
      Mortality and morbidity rates did not differ across BMI categories. Obesity
      should not be considered a risk factor for adverse outcomes after CABG and should
      not be a contraindication for surgery.

PMID- 24316994
TI  - Therapeutic options in the management of obesity.
AB  - In New Zealand 28.4% of adults now classify as obese, whilst a total of 63.8% are
      overweight or obese (BMI >25 kg/m2). This presents an ever increasing social and
      economic burden to individuals, families and the healthcare system. Obesity is a
      major risk factor for cancer, cardiovascular, metabolic, and respiratory
      disorders. Preventing obesity is the optimal long-term population strategy and
      must be a government priority. There are many approaches which could be taken to
      facilitate this, however it is important not to forget those who are currently
      overweight or obese. This review addresses the current therapeutic options in the
      treatment of obesity, focusing on lifestyle changes, medications, and surgery in
      New Zealand. It also presents a suggested algorithm for the clinician assessing
      and managing obese patients in New Zealand.

PMID- 24316995
TI  - Improving the New Zealand dairy industry's contribution to local and global
      wellbeing: the case of infant formula exports.
AB  - On narrow economic measures of wellbeing, New Zealand's dairy industry is a huge
      success. Infant formula, in particular, is New Zealand's 'export superstar'.
      However, using a broader wellbeing lens, there is some public disquiet about
      environmental, human and animal wellbeing associated with the dairy industry.
      This article questions whether New Zealand's dairy industry is also undermining
      global 'best practice' infant feeding. It argues that while there is support for
      increased trade and exports, there are few voices promoting global infant health
      and that discussion is needed on this issue by the New Zealand public health
      community. 

PMID- 24316996
TI  - A glucose meter evaluation co-designed with both health professional and consumer
      input.
AB  - Health consumer's input into assessment of medical device safety is traditionally
      given either as part of study outcome (trial participants) or during post
      marketing surveillance. Direct consumer input into the methodological design of
      device assessment is less common. We discuss the difference in requirements for
      assessment of a measuring device from the consumer and clinician perspectives,
      using the example of hand held glucose meters. Around 80,000 New Zealanders with
      diabetes recently changed their glucose meter system, to enable ongoing access to
      PHARMAC subsidised meters and strips. Consumers were most interested in a direct
      comparison of their 'old' meter system (Accu-Chek Performa) with their 'new'
      meter system (CareSens brand, including the CareSens N POP), rather than
      comparisons against a laboratory standard. This direct comparison of meter/strip
      systems showed that the CareSens N POP meter read around 0.6 mmol/L higher than
      the Performa system. Whilst this difference is unlikely to result in major errors
      in clinical decision making such as major insulin dosing errors, this information
      is nevertheless of interest to consumers who switched meters so that they could
      maintain access to PHARMAC subsidised meters and strips. We recommend that when
      practical, the consumer perspective be incorporated into study design related to
      medical device assessment.

PMID- 24316997
TI  - Angiostrongylus meningitis associated with intraparenchymal cerebral haemorrhage.
AB  - Angiostrongylus cantonensis (A. cantonensis) is a nematode parasite found in
      Southeast Asia, Australia and the Pacific that is the most common cause of
      eosinophilic meningitis. We report a case of intraparenchymal cerebral
      haemorrhage associated with A. cantonensis meningitis. This complication has not
      previously been reported in the literature. 

PMID- 24316998
TI  - Portal vein thrombosis as a complication of laparoscopic sleeve gastrectomy.
AB  - Laparoscopic sleeve gastrectomy (LSG) is a popular form of weight loss surgery in
      New Zealand. The current case report describes an incident of portal vein
      thrombosis (PVT) following this surgery and serves to increase the understanding
      of the unique risks of this operation. 

PMID- 24316999
TI  - Pure red cell aplasia associated with recombinant erythropoietin: a case report
      and brief review of the literature.
AB  - Pure red cell aplasia (PRCA) is a rare adverse effect of recombinant
      erythropoietin (rEPO). Affected patients rapidly become transfusion-dependent,
      with many requiring immunosuppressive therapy for remission. We report a
      confirmed case in an elderly female, possibly the first of its kind in New
      Zealand, who was started on rEPO for anaemia of chronic kidney disease. We also
      briefly review current literature on rEPO-associated PRCA. 

PMID- 24317000
TI  - Medical image. An unusual case of melaena.
AB  - Metastatic melanoma can present with non-cutaneous symptoms even after several
      years of remission. Although poor prognosis, surgical resection and arterial
      embolisation can provide effective symptom palliation.

PMID- 24317001
TI  - Drowning terminology: not what it used to be.

PMID- 24317002
TI  - Helmet use by skiers and snowboarders in New Zealand.

PMID- 24317003
TI  - Leading the way with a health research repository.

PMID- 24317004
TI  - 50th anniversary of the modern use of intravenous regional anaesthesia.

PMID- 24317005
TI  - The elderly locum.

PMID- 24317006
TI  - Missed tobacco tax revenue from 'foreign' packs in New Zealand: results from a
      discarded pack collection study.

PMID- 24317007
TI  - Particularizing the general: Sustaining theoretical integrity in the context of
      an evidence-based practice agenda.
AB  - Proliferation of demands for accountability and health care quality places nurses
      under constant pressure to ensure professional practice is evidence-based. The
      corresponding emphasis on knowledge that pertains to general populations
      challenges nursing's traditional focus on the uniqueness of each individual
      patient. Considering how nurses engage with professional systematic thinking
      processes, we reflect on ways competing agendas in the evidence-based practice
      environment compromise the professional vision aspired to by an earlier era of
      nursing model and framework builders. Exploring the scientific thinking
      underpinning practice evidence, we contemplate implications for applying general
      knowledge to particular practice, reconsidering options for conceptualizing
      nursing praxis.

PMID- 24317008
TI  - Detection of DNA hypermethylation in sera of patients with Crohn's disease.
AB  - Mounting evidence suggests that inflammatory bowel disease (IBD) is caused by
      genetic predisposition of various genes as well as an abnormal interaction with
      environmental factors, resulting in epigenetic alterations. It has become evident
      that epigenetic factors play a significant contributory role during disease
      development. Additionally, DNA methylation has been reported to be correlated
      with the development of IBD. In the present study, we examined the role of DNA
      hypermethylation in Crohn's disease (CD) patients. The transcription elongation
      regulator 1-like (TCERG1L) gene, which has been previously reported to be highly
      frequently methylated in colon tumors was selected as a candidate for the early
      detection of biomarkers for colon cancer patients. DNA methylation of TCERG1L in
      101 serum samples of CD patients was examined. Results of conventional MSP
      analysis revealed high methylation [57% (58/101)] of serum samples in CD
      patients. The DNA methylation pattern of TCEEG1L was confirmed using bisulfate
      sequencing analysis. The results of the present study suggest that using regular
      colonoscopic surveillance sensitive DNA methylation markers may detect serum
      samples of CD patients, leading to reduced risk or prevention of the progression
      of advanced stages of disease.

PMID- 24317009
TI  - Fluoromethylated derivatives of carnitine biosynthesis intermediates--synthesis
      and applications.
AB  - A convenient method for the synthesis of fluoromethylated carnitine biosynthesis
      intermediates, i.e. fluorinated derivatives of gamma-butyrobetaine and
      trimethyllysine, is described. The fluoromethylated probes were useful in both in
      vitro and cell based assays employing (19)F NMR and LC-MS analyses. 

PMID- 24317010
TI  - Intriguing surface-extruded plastic flow of SiOx amorphous nanowire as athermally
      induced by electron beam irradiation.
AB  - Nanoinstability and nanoprocessing of a SiOx amorphous nanowire at room
      temperature as induced by in situ electron beam irradiation in transmission
      electron microscopy are systematically investigated. It is demonstrated that in
      contrast to the crystalline nanowires where only the beam-induced ablation of
      atoms was observed, the amorphous nanowire herein can give rise to an arresting
      beam-induced surface-extruded plastic flow of massive atoms and surface migration
      of atoms in addition to the beam-induced ablation of atoms. Via the plastic flow
      and ablation, a new S-type deformed wire and the thinnest amorphous nanowire are
      elaborately created locally at nanoscale precision with a highly controllable
      manner depending on the beam current density, beam spot size, and beam position.
      The existing knock-on mechanism and simulation seem inadequate to explain these
      processes. However, it is indicated that a much higher nanocurved surface energy
      of nanowires and an enhanced beam-induced soft mode and instability of atomic
      vibration control the processes. 

PMID- 24317011
TI  - Ameliorative effect of Pracparatum mungo extract on high cholesterol diets in
      hamsters.
AB  - This study was designed to test the lipid-lowering and antioxidative activities
      of Pracparatum mungo extract (PME), in comparison to its components berberine and
      glycyrrhizin in cholesterol-fed hamsters. The PME and berberine significantly
      lowered the atherogenic index compared to glycyrrhizin and the control (P <
      0.05). The hepatic HMG-CoA reductase activity was significantly lower in the PME
      and berberine groups than in the glycyrrhizin group (P < 0.05), while the hepatic
      ACAT activity was significantly decreased by all treatments with respect to the
      high cholesterol fed group (P < 0.05). The overall potential of the antioxidant
      system was significantly enhanced by the PME, berberine and glycyrrhizin
      supplements as the plasma and hepatic TBARS levels were lowered while the hepatic
      superoxide dismutase activity and glutathione levels, HMG-CoA reductase, LDL
      receptor, PPAR, SREBP-2 and CYP7A1 mRNA expressions were increased by the
      treatments of PME and berberine in comparison with the high cholesterol fed
      hamsters (P < 0.05). Collectively, these results suggest that the supplementation
      of PME, berberine and glycyrrhizin increased antioxidant activity in hamsters.
      Furthermore, we observed that PME and berberine groups promoted the excretion of
      neutral and acidic sterols (P < 0.05), that could contribute to explain the lower
      plasma and hepatic cholesterol levels found in the treated animals. 

PMID- 24317015
TI  - Pallister-Killian syndrome: a common yet under-recognised cause of epileptic
      spasms.

PMID- 24317012
TI  - The role of reduced intracellular concentrations of active drugs in the lack of
      response to anticancer chemotherapy.
AB  - A major difficulty in the treatment of cancers is the poor response of many
      tumors to pharmacological regimens. This situation can be accounted for by the
      existence of a variety of complex mechanisms of chemoresistance (MOCs), leading
      to reduced intracellular concentrations of active agents, changes in the
      molecular targets of the drugs, enhanced repair of drug-induced modifications in
      macromolecules, stimulation of anti-apoptotic mechanisms, and inhibition of pro
      apoptotic mechanisms. The present review focuses on alterations in the expression
      and appearance of the genetic variants that affect the genes involved in reducing
      the amount of active agents inside tumor cells. These alterations can occur
      through two mechanisms: either by lowering uptake or enhancing efflux (so-called
      MOC-1a and MOC-1b, respectively), or by decreasing the activation of prodrugs or
      enhancing inactivation of active agents through their biotransformation (MOC-2).
      The development of chemosensitizers that are useful in implementing the
      pharmacological manipulation of these processes constitutes a challenge to modern
      pharmacology. Nevertheless, the important physiological roles of the most
      relevant genes involved in MOC-1a, MOC-1b, and MOC-2 make it difficult to prevent
      the side effects of chemosensitizers. A more attainable goal in this area of
      pharmacological enquiry is the identification of proteomic profiles that will
      permit oncologists to accurately predict a lack of response to a given regimen,
      which would be useful for adapting treatment to the personal situation of each
      patient. 

PMID- 24317016
TI  - Effect of leukemia inhibitory factor and forskolin on establishment of rat
      embryonic stem cell lines.
AB  - This study was designed to investigate whether supplementation of 2i medium with
      leukemia inhibitory factor (LIF) and/or forskolin would support establishment of
      germline-competent rat embryonic stem (ES) cell lines. Due to the higher
      likelihood of outgrowth rates, supplementation of forskolin with or without LIF
      contributed to the higher establishment efficiency of ES cell lines in the WDB
      strain. Germline transmission competency of the chimeric rats was not influenced
      by the profile of ES cell lines until their establishment. When the LIF/forskolin
      supplemented 2i medium was used, the rat strain used as the blastocyst donor,
      such as the WI strain, was a possible factor negatively influencing the
      establishment efficiency of ES cell lines. Once ES cell lines were established,
      all lines were found to be germline-competent by a progeny test in chimeric rats.
      In conclusion, both LIF and forskolin are not essential but can play a beneficial
      role in the establishment of "genuine" rat ES cell lines. 

PMID- 24317017
TI  - Theoretical simulation of temperature elevations in a joint wear simulator during
      rotations.
AB  - The objective of this study is to develop a theoretical model to simulate
      temperature fields in a joint simulator for various bearing conditions using
      finite element analyses. The frictional heat generation rate at the interface
      between a moving pin and a stationary base is modeled as a boundary heat source.
      Both the heat source and the pin are rotating on the base. We are able to conduct
      a theoretical study to show the feasibility of using the COMSOL software package
      to simulate heat transfer in a domain with moving components and a moving
      boundary source term. The finite element model for temperature changes agrees in
      general trends with experimental data. Heat conduction occurs primarily in the
      highly conductive base component, and high temperature elevation is confined to
      the vicinity of the interface in the pin. Thirty rotations of a polyethylene pin
      on a cobalt-chrome base for 60 s generate more than 2.26  degrees C in the
      temperature elevation from its initial temperature of 25  degrees C at the
      interface in a baseline model with a rotation frequency of 0.5 Hz. A higher heat
      generation rate is the direct result of a faster rotation frequency associated
      with intensity of exercise, and it results in doubling the temperature elevations
      when the frequency is increased by100%. Temperature elevations of more than 7.5 
      degrees C occur at the interface when the friction force is tripled from that in
      the baseline model. The theoretical modeling approach developed in this study can
      be used in the future to test different materials, different material
      compositions, and different heat generation rates at the interface under various
      body and environmental conditions. 

PMID- 24317018
TI  - SCN5A mutation in Chinese patients with arrhythmogenic right ventricular
      dysplasia.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is a genetically
      determined disorder, characterized by two components: cardiomyopathy and
      arrhythmia. To date, the ion channel-related pathogenesis underlying this
      phenomenon has been poorly understood. The aim of this study was to
      systematically evaluate the sodium channel variants in Chinese patients with
      ARVD. PATIENTS AND METHODS: Patients meeting the diagnostic guidelines of ARVD
      revised in 2010 were enrolled. All exons and exon-intron boundaries of the SCN5A
      gene and desmosomal genes known to be associated with ARVD, including DSC2, DSG2,
      DSP, JUP, and PKP2, were sequenced by direct DNA sequencing. A total of 12
      unrelated index patients were included in the study. RESULTS: Eight of the
      patients developed ventricular tachycardia (VT) and ventricular fibrillation
      (VF), one of them showed epsilon wave, one of them showed type-1 Brugada wave,
      seven of them exhibited syncope or dizziness, and none of the patients had a
      family history of SCD. A new missense heterozygote mutation, I137M, in SCN5A was
      found in proband 5 with recurrent palpitations and a high incidence of VT. I137M
      is in exon 4 of SCN5A, at the S1 segment in domain I of Nav1.5, which predicted a
      substitution of isoleucine for methionine at codon site 137 (p. Ile137Met,
      I137M). I137M was not detected in 400 healthy control chromosomes from
      individuals of the same ethnic background, which indicated that this mutation was
      a conservative site in the SCN5A gene, and the encoded protein Nav1.5 might have
      a functional defect resulting in arrhythmia. CONCLUSION: This was the first study
      to systematically investigate sodium channel variants in Chinese patients with
      ARVD; a new SCN5A mutation, I137M, was found. This finding may provide new
      evidence of the genetic pathogenesis of ARVD in Chinese patients, implying that
      the SCN5A gene should be screened in patients with ARVD and VT/VF.

PMID- 24317019
TI  - Pulmonary arterial systolic pressure and E/e' in the evaluation of left
      ventricular filling pressure: assessment of patients with atrial fibrillation.
AB  - BACKGROUND: Echocardiographic assessments including E/e' are a good predictor of
      elevated left ventricular (LV) filling pressure during sinus rhythm. However, the
      evaluation of LV filling pressure using classic echocardiographic assessment has
      been challenging in the setting of atrial fibrillation (AF). The aim of this
      study was to investigate the methods for predicting LV filling pressure in
      patients with chronic AF. PATIENTS AND METHODS: Clinical data, echocardiography
      findings, and brain natriuretic peptide (BNP) levels were assessed in 59 patients
      with chronic AF who were undergoing diagnostic left-heart catheterization. LV end
      diastolic filling pressure (LVEDP) and standard echocardiographic measurements
      including pulmonary arterial systolic pressure (PASP) were evaluated. Blood
      samples were taken for serum BNP measurements within 24 h of the
      echocardiographic examination. RESULTS: E/e' correlated well with LVEDP (r =
      0.558, p < 0.001). Using receiver operating characteristic analysis, the optimal
      cut-off for E/e' was 16 (sensitivity, 64 %; specificity, 82 %) to predict LVEDP
      of > 15 mmHg. PASP was also well correlated with LVEDP (r = 0.503, p < 0.001).
      PASP greater than 32 mmHg predicted elevated LVEDP (> 15 mmHg) with a sensitivity
      of 64 % and a specificity of 71 %. CONCLUSION: E/e' and PASP were well correlated
      with LVEDP in patients with AF. PASP greater than 32 mmHg and E/e' greater than
      16 may suggest elevated LVEDP (> 15 mmHg) in patients with chronic AF.

PMID- 24317020
TI  - Latest-generation catheterization systems enable invasive submillisievert
      coronary angiography.
AB  - BACKGROUND: The radiation risk of patients undergoing invasive cardiology remains
      considerable and includes skin injuries and cancer. To date, submillisievert
      coronary angiography has not been considered feasible. PATIENTS AND METHODS: In
      2011, we compared results from 100 consecutive patients undergoing elective
      coronary angiography using the latest-generation flat-panel angiography system
      (FPS) with results from examinations by the same operator using 106 historic
      controls with a conventional image-intensifier system (IIS) that was new in 2002.
      RESULTS: The median patient exposure parameters were measured as follows: dose
      area product (DAP) associated with radiographic cine acquisitions (DAP(R)) and
      fluoroscopy (DAP(F)) scenes, radiographic frames and runs, and cumulative
      exposure times for radiography and fluoroscopy. On the FPS as compared to the
      traditional IIS, radiographic detector entrance dose levels were reduced from 164
      to 80 nGy/frame and pulse rates were lowered from 12.5/s to 7.5/s during
      radiography and from 25/s to 4/s during fluoroscopy. The cardiologist's
      performance patterns remained comparable over the years: fluoroscopy time was
      constant and radiography time even slightly increased. Overall patient DAP
      decreased from 7.0 to 2.4 Gy * cm(2); DAP(R), from 4.2 to 1.7 Gy * cm(2); and
      DAP(F), from 2.8 to 0.6 Gy * cm(2). Time-adjusted DAP(R)/s decreased from 436 to
      130 mGy * cm(2) and DAP(F)/s, from 21.6 to 4.4 mGy * cm(2). Cumulative patient
      skin dose with the FPS amounted to 67 mGy, and the median (interquartile range)
      of effective dose was 0.5 (0.3 ... 0.7) mSv. CONCLUSION: Consistent application
      of radiation-reducing techniques with the latest-generation flat-panel systems
      enables submillisievert coronary angiography in invasive cardiology.

PMID- 24317021
TI  - Drinking water quality and formation of biofilms in an office building during its
      first year of operation, a full scale study.
AB  - Complex interactions existing between water distribution systems' materials and
      water can cause a reduction in water quality and unwanted changes in materials,
      aging or corrosion of materials and formation of biofilms on surfaces. Substances
      leaching from pipe materials and water fittings, as well as the microbiological
      quality of water and formation of biofilms were evaluated by applying a Living
      Lab theme i.e. a research in a real life setting using a full scale system during
      its first year of operation. The study site was a real office building with one
      part of the building lined with copper pipes, the other with cross-linked
      polyethylene (PEX) pipes thus enabling material comparison; also differences
      within the cold and hot water systems were analysed. It was found that
      operational conditions, such as flow conditions and temperature affected the
      amounts of metals leaching from the pipe network. In particular, brass components
      were considered to be a source of leaching; e. g. the lead concentration was
      highest during the first few weeks after the commissioning of the pipe network
      when the water was allowed to stagnate. Assimilable organic carbon (AOC) and
      microbially available phosphorus (MAP) were found to leach from PEX pipelines
      with minor effects on biomass of the biofilm. Cultivable and viable biomass
      (heterotrophic plate count (HPC), and adenosine triphosphate (ATP)) levels in
      biofilms were higher in the cold than in the hot water system whereas total
      microbial biomass (total cell count (DAPI)) was similar with both systems. The
      type of pipeline material was not found to greatly affect the microbial biomass
      or Alpha-, Beta- and Gammaproteobacteria profiles (16s rRNA gene copies) after
      the first one year of operation. Also microbiological quality of water was found
      to deteriorate due to stagnation. 

PMID- 24317022
TI  - Factors that influence properties of FOG deposits and their formation in sewer
      collection systems.
AB  - Understanding the formation of Fat, Oil, and Grease (FOG) deposits in sewer
      systems is critical to the sustainability of sewer collection systems since they
      have been implicated in causing sewerage blockages that leads to sanitary sewer
      overflows (SSOs). Recently, FOG deposits in sewer systems displayed strong
      similarities with calcium-based fatty acid salts as a result of a saponification
      reaction. The objective of this study was to quantify the factors that may affect
      the formation of FOG deposits and their chemical and rheological properties.
      These factors included the types of fats used in FSEs, environmental conditions
      (i.e. pH and temperature), and the source of calcium in sewer systems. The
      results of this study showed that calcium content in the calcium based salts
      seemed to depend on the solubility limit of the calcium source and influenced by
      pH and temperature conditions. The fatty acid profile of the calcium-based fatty
      acid salts produced under alkali driven hydrolysis were identical to the profile
      of the fat source and did not match the profile of field FOG deposits, which
      displayed a high fraction of palmitic, a long chain saturated fatty acid. It is
      hypothesized that selective microbial metabolism of fats and/or biologically
      induced hydrogenation may contribute to the FOG deposit makeup in sewer system.
      Therefore, selective removal of palmitic in pretreatment processes may be
      necessary prior to the discharge of FSE wastes into the sewer collection system. 

PMID- 24317023
TI  - Quantitative determination of E-N-carboxymethyl-L-lysine in human plasma by
      liquid chromatography-tandem mass spectrometry.
AB  - E-N-carboxymethyl-L-lysine (CML) is a stable chemical modification of protein
      lysine residues resulting from glycation and oxidation reactions and a potential
      biomarker of oxidative stress caused by sugar and lipid oxidation. In this study,
      a rapid, simple and sensitive method based on liquid chromatography-tandem
      spectrometry (LC-MS/MS) for the determination of CML in human plasma has been
      developed and validated. Sample preparation involved protein precipitation using
      trichloroacetic acid after addition of deuterated CML as internal standard.
      Chromatography was performed on an amino column by gradient-elution with a mobile
      phase containing acetonitrile:ultrapure water (80:20, v/v). CML and CML-d2 were
      detected by multiple reaction monitoring mode with ion pairs 205.0/130.1 and
      207.2/84.1 respectively. The assay was linear in the range 10-1000 ng/mL with a
      lower limit of quantitation (LLOQ) of 10 ng/mL and recovery >90%. Assay
      validation showed that inter- and intra-day precision and accuracy were
      satisfactory. The method was applied to compare plasma CML levels in healthy
      Chinese subjects and patients with diabetes and uremia. In healthy subjects CML
      concentration (mean+/-SD) was 16.6+/-7.8 ng/mL. CML level in diabetic patients
      was not significantly different from healthy subjects whereas the level in
      patients with uremia was significantly higher than both healthy subjects and
      diabetic patients (P<0.001). The method will be useful to assess the value of CML
      as a biomarker of diabetic vascular complications resulting from elevated
      oxidative stress.

PMID- 24317024
TI  - Quantitative determination of azacitidine triphosphate in peripheral blood
      mononuclear cells using liquid chromatography coupled with high-resolution mass
      spectrometry.
AB  - Azacitidine is a cytidine analog used in the treatment of myelodysplastic
      syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia. The
      pharmacological effect of azacitidine arises after incorporation into the DNA and
      RNA. To this end, the drug first has to be converted into its triphosphate forms.
      This paper describes the development of an assay for quantitative determination
      of azacitidine triphosphate (aza-CTP) in peripheral blood mononuclear cells
      (PBMCs). To quantify aza-CTP, separation from the endogenous nucleotides cytidine
      triphosphate (CTP) and uridine triphosphate (UTP) is required. This was a
      challenge as the structures of these nucleotides are highly similar and the
      monoisotopic molecular masses of aza-CTP, UTP and the naturally occurring [(13)C]
      and [(15)N]-isotopes of CTP differ less than 0.02 Da. Efforts to select a
      specific MS(2)-fragment for aza-CTP using a triple quadrupole mass spectrometer
      remained without success. Therefore, we investigated the feasibility to separate
      these highly resembling nucleotides based on accurate mass spectrometry using a
      linear trap quadrupole (LTQ) coupled with an Orbitrap. The LTQ-Orbitrap was able
      to differentiate between aza-CTP and the endogenous nucleotides UTP and [(13)C]
      CTP. There was no baseline resolution between aza-CTP and [(15)N]-CTP, but the
      [(15)N]-CTP interference was low. For quantification, extracted ion chromatograms
      were obtained for the accurate m/z window of the aza-CTP product ion. The assay
      was able to determine aza-CTP concentrations in PBMC lysate from 40.7 to 281 nM.
      Assuming that an average cell suspension extracted from 16 mL blood contains 10
      to 42 million PBMCs per mL, this range corresponds with 2.58/10.9-17.8/74.9 pmol
      aza-CTP per million PBMCs. Intra-assay accuracies were between -1.1 and 9.5%
      deviation and coefficient of variation values were <=13.2%. The assay was
      successfully applied to quantify aza-CTP in samples from two patients treated
      with azacitidine. Aza-CTP concentrations up to 19.0 pmol per million PBMCs were
      measured. This is the first time that aza-CTP concentrations were quantified in
      PBMCs from patients treated with azacitidine.

PMID- 24317025
TI  - From the editor.

PMID- 24317026
TI  - Guest editorial.

PMID- 24317027
TI  - The coming revolution in personal care robotics: what does it mean for nurses?
AB  - The business sector provides regular reportage on the development of personal
      care robots to enable elders and people with disabilities to remain in their
      homes. Technology in this area is advancing rapidly in Asia, Europe, and North
      America. To date, the nursing literature has not addressed how nurses will assist
      these vulnerable populations in the selection and use of robotic technology or
      how robotics could effect nursing care and patient outcomes. This article
      provides an overview of development in the area of personal care robotics to
      address societal needs reflecting demographic trends. Selected relevant issues
      related to the human-robotic interface including ethical concerns are identified.
      Implications for nursing education and the delivery of nursing services are
      identified. Collaboration with engineers in the development of personal care
      robotic technology has the potential to contribute to the creation of products
      that optimally address the needs of elders and people with disabilities. 

PMID- 24317028
TI  - People, technology, and process meet the triple aim.
AB  - Banner Health is addressing the Triple Aim (quality care and satisfaction,
      improved health, and reduced cost) for Medicare beneficiaries by combining the
      people of one of the largest nonprofit health care systems in the United States
      (Banner Health) with innovative telehealth technology and leveraging high
      reliability, standardized processes. The program, known as Banner iCare, builds
      on a highly successful tele-ICU program (some of the lowest mortality and length
      of stay results in the country) and expands the service to progressive care,
      medical-surgical, and emergency departments. These successes have led to the
      introduction of a home-based telehealth program with the strengths of the acute
      care programs. The top 5% high-cost patients with multiple chronic conditions
      receive coordinated intensive ambulatory care managed by an integrated team of
      health care professionals using cost-effective telehealth technology. The
      benefits expected from the proposed project include a reduction in overall costs
      while improving patient satisfaction through delivery of more personalized and
      interactive care. 

PMID- 24317029
TI  - The future shortage of doctoral prepared nurses and the impact on the nursing
      shortage.
AB  - Nursing remains at the top of the job growth market and has the potential to
      positively or negatively impact changes in the delivery of health care today.
      Professional nurses play a crucial role in the prevention of medication errors,
      decreasing infection rates, and facilitating a patient's safe transition from
      acute care into the home environment. Nurses must make critical life-saving
      decisions associated with caring for the more acutely ill patient. Doctoral
      prepared nurses have the unique position to assist the direct care nurse because
      of their advanced education. The doctor in nursing practice concentrates on
      direct care, specifically research utilization for improved delivery of care,
      patient outcomes, and clinical systems management There is a future shortage of
      doctoral prepared nurses, and a resolution is needed. Doctoral prepared nurses
      with advanced degrees play an important role in mentoring the bedside nurse to
      promote an interdisciplinary collaborative relationship. The doctor in nursing
      practice has the ability to effect change in health care systems, organizations,
      and policy through focusing on the essence of nursing-the care. 

PMID- 24317030
TI  - "On the scene": Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
AB  - Cincinnati Children's Hospital Medical Center is transforming the way it cares
      for its patients by building a sophisticated model that focuses on accountable
      care across the continuum. As nurses from different parts of the organization, we
      act as change agents to develop an integrated structure built around the
      patient's needs, from prevention to self-management. We demonstrate how
      organizational structure, fluid staffing, professional practice, and healthy
      behaviors operationally catalyze the continuum of care, and how we utilize self
      management, community-based programs, and care integration to change the outcome
      for our patients and families. While care coordination is taking on many forms in
      medical centers around the world, Cincinnati Children's is proud and passionate
      about sharing its best practices along the way. 

PMID- 24317031
TI  - Virtual nursing grand rounds and shared governance: how innovation and
      empowerment are transforming nursing practice at Thanh Nhan Hospital, Hanoi,
      Vietnam.
AB  - The Vietnam Nurse Project has been operating in Hanoi since 2007. Its primary
      purpose is to improve nursing education through curriculum development, faculty
      development, and the introduction of a more student-centric teaching and learning
      environment. The Virtual Nursing Grand Rounds component of the project is an
      academic-practice partnership between the Vietnam Nurse Project at the University
      of San Francisco School of Nursing and Health Professions and the Thanh Nhan
      Hospital intensive care unit. Its goal is to improve nursing practice in the
      Thanh Nhan Hospital intensive care unit. The Virtual Nursing Grand Rounds is a
      fully interactive real-time synchronous computer technology-assisted point-to
      point program that provides ongoing evidence-based staff development and
      consultative services. 

PMID- 24317032
TI  - Large-system acute care transformation.
AB  - All organizations are steeped in making delivery model changes to address the
      changing health care landscape specific to the expectations of health care
      reform. Too often, these changes focus solely on improving processes rather than
      developing creative and innovative work processes that decrease waste and
      increase quality. The Providence Health and Services system has embraced the
      challenge to transform health care services from a large-system perspective,
      beginning with 1 region. The authors share the beginning stages of this
      innovative work, the unique contributions to health care processes, and the early
      outcomes on 2 patient care units. 

PMID- 24317033
TI  - Workarounds and obstacles: unexpected source of innovation.
AB  - Nurse leaders are aware that nurses are finding ways to adapt health information
      technology to patient care activities. Previous literature has presented nurses'
      response to technology obstacles as a work-around, characterized as a negative
      behavior. Using narrative inquiry, this article examines 9 direct care nurses'
      interactions on a medical/surgical/telemetry unit. Specifically, nurses'
      encounters with technology obstacles will be addressed from a complexity science
      perspective. Four support staff including the clinical nurse manager, pharmacist,
      quality nurse, and project manager who is also a nurse were interviewed as part
      of data collection. Complexity science provides nurse leaders' insight into
      nurses' behavior where outcomes emerge from tensions in the environment through
      multidirectional and self-organizing interactions. Innovation was found when
      nurses responded to health information technology obstacles with self-organizing
      interactions, sensitivity to initial conditions, and multidirectionality. Their
      actions were also influenced by many sets of rules. Nurses self-organized with
      coworkers to find better ways to deliver care to patients when using technology.
      Opportunities exist for nurse leaders to facilitate interactions among nurses and
      other members of the organization to realize better use of health information
      technology that improves the patient experience. 

PMID- 24317034
TI  - Leaders: are you ready for change? The clinical nurse as care coordinator in the
      new health care system.
AB  - Care coordination is an integral piece for the success of health care reform.
      Nurses are positioned to be able to bring a strong perspective for assisting
      individual's health needs across the continuum from illness to wellness.
      Currently, nurses are not consistently being fully prepared to provide care
      coordination. In order for clinical nurses in acute care, clinics, and across the
      care continuum to be able to perform this integral and emerging role, nurse
      leaders will need to restructure, engage with these nursing roles, and plan to
      provide resources for a new educational curriculum for their continuing
      professional development. 

PMID- 24317035
TI  - Creating national standards from the point of care.
AB  - Every nurse leader is challenged to provide an infrastructure for patient care
      that facilitates the highest quality of patient care services, the adoption of
      innovative practices, and the satisfaction of caregivers. Nurses are expected to
      provide the best possible care to patients and their families in ways that are
      safe, respectful, timely, and appropriate, even if there is not a specific policy
      to support it-all within the scope of practice. The purpose of this article is to
      share an exemplar that illustrates an effective change dynamic as the framework
      for changing nursing practice. The exemplar describes a new approach for
      postmortem care that began with creative problem solving at the bedside and
      evolved to a nurse-led research study. Results from the study continue to be
      disseminated with the intention that the nursing intervention will become
      standard of care. 

PMID- 24317036
TI  - Social media creates significant risks for nursing.
AB  - As nurses' use of social media becomes prevalent, nurse leaders continue to
      struggle with how best to embrace this communications platform while protecting
      the confidentiality of patient data. Nursing leadership must move decisively to
      balance its social media policies and practices against the need for information
      to move quickly and efficiently across the continuum of care. 

PMID- 24317037
TI  - Regulatory issues for the hospital system chief nursing officer.

PMID- 24317038
TI  - Two waves of distinct hematopoietic progenitor cells colonize the fetal thymus.
AB  - The generation of T cells depends on the migration of hematopoietic progenitor
      cells to the thymus throughout life. The identity of the thymus-settling
      progenitor cells has been a matter of considerable debate. Here we found that
      thymopoiesis was initiated by a first wave of T cell lineage-restricted
      progenitor cells with limited capacity for population expansion but accelerated
      differentiation into mature T cells. They gave rise to alphabeta and gammadelta T
      cells that constituted Vgamma3(+) dendritic epithelial T cells. Thymopoiesis was
      subsequently maintained by less-differentiated progenitor cells that retained the
      potential to develop into B cells and myeloid cells. In that second wave, which
      started before birth, progenitor cells had high proliferative capacity but
      delayed differentiation capacity and no longer gave rise to embryonic gammadelta
      T cells. Our work reconciles conflicting hypotheses on the nature of thymus
      settling progenitor cells. 

PMID- 24317039
TI  - Inhibition of the kinase Csk in thymocytes reveals a requirement for actin
      remodeling in the initiation of full TCR signaling.
AB  - Signaling via the T cell antigen receptor (TCR) is initiated by Src-family
      kinases (SFKs). To understand how the kinase Csk, a negative regulator of SFKs,
      controls the basal state and the initiation of TCR signaling, we generated mice
      that express a Csk variant sensitive to an analog of the common kinase inhibitor
      PP1 (Csk(AS)). Inhibition of Csk(AS) in thymocytes, without engagement of the
      TCR, induced potent activation of SFKs and proximal TCR signaling up to
      phospholipase C-gamma1 (PLC-gamma1). Unexpectedly, increases in inositol
      phosphates, intracellular calcium and phosphorylation of the kinase Erk were
      impaired. Altering the actin cytoskeleton pharmacologically or providing
      costimulation via CD28 'rescued' those defects. Thus, Csk has a critical role in
      preventing TCR signaling. However, our studies also revealed a requirement for
      actin remodeling, initiated by costimulation, for full TCR signaling. 

PMID- 24317041
TI  - Compound heterozygous hemophilia A in a female patient and the identification of
      a novel missense mutation, p.Met1093Ile.
AB  - Hemophilia A (HA) in females is rare. Female HA cases are often misdiagnosed as
      acquired HA (AHA) or as von Willebrand disease type 2N (vWD-2N). Here, we report
      the case of a 37-year-old female HA patient with a moderate factor VIII (FVIII)
      deficiency. The patient had no personal or family history of bleeding disorders,
      but presented with heavy uterine bleeding following surgery to remove an
      intrauterine device. IgG inhibitory antibodies against FVIII were undetected. A
      compound heterozygote mutation of the FVIII gene (F8) was found in this patient.
      The p.Val502Asp mutation, which has been reported previously, affects A2 domain
      function. A novel missense point mutation, p.Met1093Ile, was identified in the B
      domain. The compound heterozygote mutations in F8, p.Val502Asp and p.Met1093Ile,
      caused HA in this female patient, with a moderate phenotype.

PMID- 24317042
TI  - Optimal Input Signal Design for Data-Centric Estimation Methods.
AB  - Data-centric estimation methods such as Model-on-Demand and Direct Weight
      Optimization form attractive techniques for estimating unknown functions from
      noisy data. These methods rely on generating a local function approximation from
      a database of regressors at the current operating point with the process repeated
      at each new operating point. This paper examines the design of optimal input
      signals formulated to produce informative data to be used by local modeling
      procedures. The proposed method specifically addresses the distribution of the
      regressor vectors. The design is examined for a linear time-invariant system
      under amplitude constraints on the input. The resulting optimization problem is
      solved using semidefinite relaxation methods. Numerical examples show the
      benefits in comparison to a classical PRBS input design.

PMID- 24317040
TI  - High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages
      via the transcriptional regulator ATF3.
AB  - High-density lipoprotein (HDL) mediates reverse cholesterol transport and is
      known to be protective against atherosclerosis. In addition, HDL has potent anti
      inflammatory properties that may be critical for protection against other
      inflammatory diseases. The molecular mechanisms of how HDL can modulate
      inflammation, particularly in immune cells such as macrophages, remain poorly
      understood. Here we identify the transcriptional regulator ATF3, as an HDL
      inducible target gene in macrophages that downregulates the expression of Toll
      like receptor (TLR)-induced proinflammatory cytokines. The protective effects of
      HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in
      vivo. Our findings may explain the broad anti-inflammatory and metabolic actions
      of HDL and provide the basis for predicting the success of new HDL-based
      therapies. 

PMID- 24317043
TI  - MicroRNAs contribute to the anticancer effect of 1'-acetoxychavicol acetate in
      human head and neck squamous cell carcinoma cell line HN4.
AB  - 1'-Acetoxychavicol acetate (ACA), extracted from rhizomes of tropical ginger,
      possesses antitumor properties against a wide variety of malignancies. MicroRNAs
      have been found to act as oncogenes and as tumor suppressor genes in the
      development of cancer. The purpose of this study was to investigate the miRNA
      involved in the molecular mechanisms of ACA action on tumor inhibition. It was
      found that ACA significantly inhibited the growth of human head and neck squamous
      cell carcinoma cell line HN4 and induced cell apoptosis. Further studies
      indicated that ACA downregulated the expression of miR-23a in HN4 cells.
      Transfection with anti-miR-23a inhibited the proliferation of HN4 cells and
      induced cell apoptosis. In addition, phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) was confirmed to be the target of miR-23a. Taken together,
      our findings suggest that ACA might have anticancer effects against human head
      and neck cancer through downregulation of miR-23a, which can repress tumor
      suppressor PTEN. 

PMID- 24317044
TI  - Characterization of lysis of the multicellular Cyanobacterium
      Limnothrix/Pseudanabaena sp. strain ABRG5-3.
AB  - The cyanobacterium semi-filamentous multicellular strain ABRG5-3 undergoes cell
      lysis as a unique feature that occurs due to growth condition changes from normal
      cultivation with shaking to static cultivation without shaking in liquid culture
      (Nishizawa et al., 2010). Microscopic observation and energy dispersive X-ray
      spectrometer (EDX) analysis have revealed that lysis is involved in the
      accumulation of polyphosphate compounds and the disintegration of thylakoid
      membranes in cells. Static cultivation, dark or red light exposure, and
      temperature (22 to 42  degrees C) conditions were found to be effective factors
      for the induction of lysis. Moreover, stress induced by salts, osmotic pressure
      with sucrose, and the depletion of nitrogen or phosphate in cultures also induced
      ABRG5-3 cell lysis. Based on these results, we discuss lysis and its utilization
      in the biotechnology industry. 

PMID- 24317045
TI  - Anti-inflammatory activities of methanol extract of Mastixia arborea C.B. Clarke
      as to mouse macrophage and paw edema.
AB  - The biological activity of Mastixia arborea (MA) relates to inflammation, but the
      underlying mechanisms are largely unknown. We confirmed the anti-inflammatory
      effects of a methanol extract of MA extract on lipopolysaccharide (LPS)
      stimulated RAW264.7 mouse macrophage cells and carrageenan-induced mice paw
      edema. The MA extract significantly inhibited nitric oxide (NO), prostaglandin E2
      (PGE2), interleukin-1beta (IL-1beta), and IL-6 production in LPS-stimulated
      RAW264.7 cells. In vitro expression of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) was suppressed by the extract. The extract attenuated
      acute inflammatory responses in carrageenan-induced mice paw edema. A mechanism
      study indicated that translocation of the NF-kappaB (p65) subunit into the
      nucleus and phosphorylation of ERK and JNK were inhibited by the extract. These
      results indicate that the extract is an effective suppressor of the inflammatory
      response, blocking the phosphorylation of ERK and JNK and the translocation of NF
      kappaB in macrophages, thereby producing an anti-inflammatory effect in vivo. 

PMID- 24317046
TI  - Production and characterization of a biosurfactant from Cyberlindnera
      samutprakarnensis JP52(T.).
AB  - Cyberlindnera samutprakarnensis JP52(T), isolated from cosmetic industrial wastes
      in Thailand, was found to be an efficient biosurfactant-producing yeast when
      cultured in a medium containing (2% (w/v) glucose and 2% (v/v) palm oil at 30 
      degrees C, 200 rpm for 7 d. The crude biosurfactant had the ability to reduce the
      surface tension from 55.7 to 30.9 mN/m at 25  degrees C with a critical micelle
      concentration (CMC) of 0.046%. Physicochemical analysis of the crude
      biosurfactant revealed that it had wide ranges of optimum pH and pH stability at
      6-9 and 3-10 respectively. It was also thermostable and retained 80% activity
      even after heat treatment, and it tolerated NaCl at 1.0-10%. Furthermore, it
      effectively emulsified various vegetable oils with an E24 value of over 80%. A
      partially purified biosurfactant fraction was analyzed for its structure by MALDI
      TOF MS and NMR. This revealed that the biosurfactant mainly contained
      sophorolipids in C18-(MW 574) and C16-diaceltylated (MW 662) forms. 

PMID- 24317047
TI  - Transient dual-luciferase assay combined with a glucocorticoid-inducible system
      for rice protoplasts.
AB  - We describe a transient dual-luciferase assay combined with a glucocorticoid
      inducible system for rice protoplasts. Luciferase genes were efficiently induced
      by adding 0.1 uM of dexamethasone to the protoplast suspension, the activity of
      the luciferases reaching a maximum 6 h after induction. This assay system is
      applicable to studying the translation efficiency of rice by using the luciferase
      gene harboring tandem copies of an interesting codon at the 5' end. 

PMID- 24317048
TI  - Effect of gamma irradiation on soybean allergen levels.
AB  - The levels of food allergens in gamma-irradiated soybean (0, 2.5, 5, 7.5, 10, 20,
      and 30 kGy) were investigated by immunoblotting and ELISA, using allergen
      specific antibodies and patient serum. After 3 months of storage, Coomassie
      brilliant blue (CBB) staining indicated similar total protein profiles among the
      treatments, but that some proteins were degraded by irradiation at high doses.
      Immunoblotting with specific antibodies for major soybean allergens (beta
      conglycinin, Gly m Bd 30 K, soybean trypsin inhibitor, and Gly m 4) resulted in
      apparent band profiles and intensities that were not significantly changed by
      irradiation. Competitive inhibition ELISA analyses suggested that there were no
      significant changes in the allergen contents, except for a decrease in the
      soybean trypsin inhibitor. The patient IgE binding allergenic protein patterns
      were not changed by irradiation up to 30 kGy. ELISA using patient serum also
      revealed that the IgE reactivity to the irradiated soybean extract did not
      increase from the level of the control, but that the reactivity to some patient
      serum IgE was significantly decreased by irradiation. 

PMID- 24317049
TI  - Cytotoxic activity of new phenolic compounds from Vietnamese Caesalpinia sappan.
AB  - Two new phenolic compounds, caesalpiniaphenols G-H (1 and 2), were isolated from
      Vietnamese Caesalpinia sappan heartwood. The chemical structures were established
      mainly by extensive spectroscopic studies and chemical evidence. Compounds 1 and
      2 showed potent inhibitory activity against HL-60 cancer cell lines with
      respective IC50 values of 16.7 and 22.5 ug/mL. Treating HL-60 cells with various
      concentrations of 1 resulted in growth inhibition and the induction of apoptosis.

PMID- 24317050
TI  - Influence of initial pH on ethanol production by the Antarctic basidiomycetous
      yeast Mrakia blollopis.
AB  - The Antarctic basidiomycetous yeast Mrakia blollopis SK-4 fermented ethanol
      between pH 5.0 and pH 10.0 with optimum pH at 8.0-10.0. Knowledge of ethanol
      fermentability as to the genus Mrakia remains incomplete. Further experiments are
      required to elucidate the ethanol fermentability of genus e.g., as to optimum
      fermentation pH, optimum fermentation temperature, and cell viability during
      fermentation. 

PMID- 24317051
TI  - Hydrogen peroxide helps in the identification of monophenols as possible
      substrates of tyrosinase.
AB  - Tyrosinase exists in three forms in the catalytic cycle depending on the
      oxidation state of the copper: met- (Em), oxy- (E(ox)), and deoxy- (Ed). When O
      quinones, products of the enzymatic reaction, evolve chemically to generate an O
      diphenol in the reaction medium, the enzyme acts on a monophenol with O-diphenol
      as reductant, converting Em to Ed. The binding of Ed to molecular oxygen gives
      E(ox), which is active on monophenols, but when the O-quinone product does not
      generate O-diphenol through chemical evolution, the monophenol does not act as an
      enzyme substrate. The fact that E(ox) can be formed from Em with hydrogen
      peroxide can be used to help identify whether a monophenol is a substrate of
      tyrosinase. The results obtained in this study confirm that compounds previously
      described as inhibitors of the enzyme are true substrates of it.

PMID- 24317052
TI  - Resveratrol-mediated reduction of collagen by inhibiting proliferation and
      producing apoptosis in human hypertrophic scar fibroblasts.
AB  - Hypertrophic scar (HS) is a dermal fibroproliferative disorder characterized by
      excessive deposition of extracellular matrix. Here, to investigate the regulative
      effects of resveratrol, a natural antioxidant compound, on fibroblasts from human
      skin HS tissue, a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      (MTT) assay was used to evaluate the inhibitory effect of resveratrol on cells.
      Cellcycle progression and apoptosis were measured by flow cytometry and Hoechst
      33258 staining respectively. The hydroxyproline content and mRNA expression
      levels of type I and III procollagen were measured separately by ELISA and
      reverse transcription-polymerase chain reaction (RT-PCR). The results indicated
      that resveratrol significantly inhibited cell growth, arresting the cell cycle at
      the G1 phase and inducing apoptosis in the fibroblasts, decreasing hydroxyproline
      (or collagen) levels, and downregulating the expression levels of type I and III
      procollagen mRNA. Taken together, these data indicate that resveratrol-mediated
      reduction of collagen in fibroblasts is at least partially effected by causing
      inhibitory cell growth, cellcycle arrest, and apoptosis, and they suggest that
      resveratrol is a potential agent for HS treatment.

PMID- 24317053
TI  - Apicidin-resistant HA22T hepatocellular carcinoma cells strongly activated the
      Wnt/beta-catenin signaling pathway and MMP-2 expression via the IGF-IR/PI3K/Akt
      signaling pathway enhancing cell metastatic effect.
AB  - The IGF-IR/PI3K/Akt signaling pathway inhibited GSK3-beta activity by
      phosphorylation and this promoted beta-catenin nuclear localization. Our previous
      study indicated that beta-catenin mRNA level was significantly higher in tumor
      areas than in non-tumor ones, especially in late pathologic stage tumors.
      However, beta-catenin inhibition resulted in significantly suppressed migration
      and invasion ability of HA22T cells. Thus, Wnt/beta-catenin pathway over
      activation might be involved in metastatic enhancement of apicidin-resistant
      HA22T cell metastasis. Apicidin-resistant (AR) HA22T cells showed higher beta
      catenin nuclear accumulation and significantly decreased GSK-3-beta protein
      level, in relation to parental cells. Results also indicated that AR cells
      increased abundantly in Tbx3, a downstream target of Wnt/beta-catenin that it is
      implicated in liver cancer. AR cells also inhibited the MEK/ERK/PEA3 pathway
      which promoted MMP-2 activation. But, apicidin-resistant effect was totally
      reversed by LY294002 and AG1024. In conclusion, Apicidin-R HA22T cells activated
      the Wnt/beta-catenin pathway and induced, MMP-2 expression via IGF-IR/PI3K/Akt
      signaling further enhancing cell the metastatic effects. 

PMID- 24317054
TI  - Biochemical analyses of the antioxidative activity and chemical ingredients in
      eight different Allium alien monosomic addition lines.
AB  - We measured the antioxidant contents and antioxidative activities in eight Allium
      fistulosum-shallot monosomic addition lines (MAL; FF+1A-FF+8A). The high
      antioxidative activity lines (FF+2A and FF+6A) showed high polyphenol
      accumulation. These additional chromosomes (2A and 6A) would therefore have
      anonymous genes related to the upregulation of polyphenol production, the
      antioxidative activities consequently being increased in these MALs. 

PMID- 24317055
TI  - Salivary nitrate and nitrite may have antimicrobial effects on Desulfovibrio
      species.
AB  - The antibacterial effects of salivary nitrate/nitrite on the growth of three
      Desulfovibrio species were examined. The bacteria did not grow on plates with >=
      0.2 mM nitrate or >= 1.0 mM nitrite. They were also incubated in filter
      sterilized saliva. D. desulfuricans was reduced on the order of >10(2) compared
      with the control solution (phosphate-buffered saline) in nine out of the 10
      participants.

PMID- 24317056
TI  - Screening of isoquinoline alkaloids for potent lipid metabolism modulation with
      Caenorhabditis elegans.
AB  - Metabolic syndrome and related disorders are increasingly prevalent in
      contemporary society, and thus pose the need for potent agents to control lipid
      accumulation in the body. This study indicates that Caenorhabditis elegans was
      effective in screening for potent lipid metabolism modulators with berberine as a
      model compound. Among the various isoquinoline alkaloids tested, sanguinarine, a
      benzophenanthridine alkaloid, was found to be the most potent. Sanguinarine, like
      berberine, reduced lipid accumulation through AMP-activated protein kinase
      activation. Analysis of AMPK (aak-1 and aak-2) RNAi worms revealed that effects
      were aak-2-dependent. Characterization of worms with knockdown nhr-49, a hormone
      nuclear receptor gene that functions as a key regulator of fat consumption,
      showed that both alkaloids were effective even in these markedly lipid
      accumulating nhr-49 RNAi worms, suggesting that they predominantly affect lipid
      synthesis, rather than fatty acid beta-oxidation. The versatility of C. elegans
      for the purpose of lipid-modulating chemical screening and characterization of
      the underlying mechanisms is discussed. 

PMID- 24317057
TI  - Effects of inhaled (S)-linalool on hypothalamic gene expression in rats under
      restraint stress.
AB  - Linalool has two enantiomers, (R)-linalool and (S)-linalool. Both are known to
      possess several biological activities in stressed animals. Our previous work
      revealed that inhalation of (R)-linalool altered hypothalamic gene expression in
      rats under stress. In the present study, we monitored hypothalamic gene
      expression in restrained rats with and without (S)-linalool inhalation by DNA
      microarray. The entire gene expression profile showed that inhalation of (S)
      linalool significantly changed the expression levels of 316 hypothalamic genes in
      the restrained rats. The differentially expressed genes (e.g., App, Avp, Igf2,
      Igfbp2, Sst and Syt5) were found to relate to cell-to-cell signaling and nervous
      system development. These results indicate that (S)-linalool influences
      hypothalamic gene expression in restrained rats, and that inhalation of (S)
      linalool under the stressed condition has some effects on stress-related
      biological responses. 

PMID- 24317058
TI  - Improved palatability and bio-functionality of super-hard rice by soaking in a
      barley-koji miso suspension.
AB  - Cooked grains of ae rice cultivars are too hard and non-sticky due to the
      presence of long-chain amylopectin, and ae rice cultivars are therefore called
      ''super-hard rice'' and cannot be used as table rice. However, they are promising
      in terms of their bio-functionality such as preventing diabetes. Miso (soybean
      paste) is a yeast-fermented food, made from steamed soybeans, salt, and
      inoculated cereals known as koji, made from rice, barley, or soybeans.We
      investigated the effects of soaking ae mutant rice cultivars in a miso
      suspension. Their chemical components, physical properties, and enzyme activities
      were measured under different conditions (milled rice before or after soaking in
      a 5% barley-koji miso suspension). Rice grains cooked after soaking in the miso
      suspension were less hard and more sticky than those cooked after soaking in
      water. Rice grains cooked after soaking in a 5% barley-koji miso suspension
      maintained high amounts of resistant starch and dietary fiber, and were fortified
      with polyphenols and isoflavones. Palatable and bio-functional ae rice could
      therefore be produced by cooking after soaking in a 5% barley-koji miso
      suspension. 

PMID- 24317059
TI  - Oral immunization of mice with lily pollen expressing HBsAg.
AB  - Lily pollen was developed to express HBsAg by Agrobacterium-mediated
      transformation. A double prime-boost strategy combining parenteral and oral HBsAg
      boosters was found to increase antibody titer levels 10-fold, as compared to a
      single process of priming and boosting. Lily pollen may prove a tool for oral
      vaccine development. 

PMID- 24317060
TI  - gamma-Mangostin from Garcinia mangostana pericarps as a dual agonist that
      activates Both PPARalpha and PPARdelta.
AB  - We tested the peroxisome proliferator-activated receptor (PPAR)delta agonistic
      activity of a Garcinia mangostana pericarp extract to develop a treatment for the
      metabolic syndrome, and demonstrated gamma-mangostin to be an active compound on
      the basis of a luciferase reporter gene assay. gamma-Mangostin induced the
      expression of the uncoupling protein-3 (UCP-3) gene which is related to energy
      expenditure and fat metabolism in L6 cells. We showed that gamma-mangostin is a
      dual agonist that activates both PPARdelta and PPARalpha. gamma-Mangostin also
      induced the expression of acyl-CoA synthase and carnitine palmitoyl-transferase
      1A genes in HepG2 cells. These results suggest the potential of gamma-mangostin
      as a preventive agent of the metabolic syndrome. 

PMID- 24317061
TI  - Production and degradation of N-acylhomoserine lactone quorum sensing signal
      molecules in bacteria isolated from activated sludge.
AB  - N-Acylhomoserine lactones (AHLs) function as quorum-sensing signaling molecules
      in many Gram-negative bacteria. We isolated a total of 672 bacterial strains from
      activated sludge obtained from seven sewage treatment plants in Tochigi
      Prefecture, Japan, and screened for AHL-producing and degrading strains. Isolates
      (n = 107) stimulated AHL-mediated purple pigment production in AHL reporter
      strains Chromobacterium violaceum CV026 and VIR07. Based on their 16S rRNA gene
      sequences, most of these AHL-producing isolates were assigned to the genus
      Aeromonas, and they were divided into six groups. Isolates (n = 46) degraded N
      decanoyl-L-homoserine lactone (C10-HSL) within 24 h. Based on their 16S rRNA gene
      sequences, the most dominant AHL-degrading isolates were assigned to the genus
      Acinetobacter and divided into six groups. Strains Ooi24, Omo91, and Uzu81, which
      showed higher C10-HSL-degrading activity, showed putative AHL-acylase activity.

PMID- 24317062
TI  - Scavenging systems for reactive carbonyls in the cyanobacterium Synechocystis sp.
      PCC 6803.
AB  - To elucidate the scavenging systems of sugar- and lipid-derived reactive
      carbonyls (RCs) in the cyanobacterium Synechocystis sp. PCC 6803 (S. 6803), we
      selected proteins from S. 6803 based on amino-acid (AA) sequence similarities
      with proteins from Arabidopsis thaliana, and characterized the properties of the
      GST-fusion proteins expressed. Slr0942 catalyzed the aldo-keto reductase (AKR)
      reaction scavenging mainly sugar-derived RCs, methylglyoxal (MG). Slr1192 is the
      medium-chain dehydrogenase/redutase (MDR). It catalyzed the AKR reaction
      scavenging several lipid-derived RCs, acrolein, propionaldehyde, and
      crotonaldehyde. Slr0315 is a short-chain dehydrogenase/redutase (SDR), and it
      catalyzed only the reduction of MG in the AKR reaction. Slr0381 catalyzed the
      conversion of hemithioacetal to S-lactoylglutahione (SLG) in the glyoxalase (GLX)
      1 reaction. Sll1019 catalyzed the conversion of SLG to glutathione and lactate in
      the GLX2 reaction. GLX1 and GLX2 compose the glyoxalase system, which scavenges
      MG. These enzymes contribute to scavenging sugar- and lipid-derived RCs as
      scavenging systems. 

PMID- 24317063
TI  - Thermal stability and starch degradation profile of alpha-amylase from
      Streptomyces avermitilis.
AB  - Amylases from Streptomyces are useful in the production of maltooligosaccharides,
      but they have weak thermal stability at temperatures higher than 40  degrees C.
      In this study, alpha-amylase (SAV5981 gene of Streptomyces avermitilis) was
      expressed from Streptomyces lividans 1326 and purified by ammonium sulfate
      fractionation followed by anionic chromatography (Q-HP sepharose). The properties
      of the purified SAV5981 amylase were determined by the starch-iodine method. The
      effect of metal ions on amylase activity was investigated. The optimal
      temperature shifted from 25 to 50  degrees C with the addition of the Ca(2+) ion.
      The thermal stability of SAV5981 was also dramatically enhanced by the addition
      of 10 mM CaCl2. Improvement of the thermal stability of SAV5981 was examined by
      CD spectra in the presence and the absence of the Ca(2+) ion. Thin-layer
      chromatography (TLC) analysis and HPLC analysis of starch degradation revealed
      that SAV5981 mainly produced maltose and maltotriose, not glucose. The
      maltoorigosaccharide-producing amylase examined in this study has the potential
      in the industrial application of oligosaccharide production.

PMID- 24317064
TI  - Transcription of ST2A encoding a sulfotransferase family protein that is involved
      in jasmonic acid metabolism is controlled according to the circadian clock- and
      PIF4/PIF5-mediated external coincidence mechanism in Arabidopsis thaliana.
AB  - Plant elongation growth on a day-to-day basis is enhanced under specific
      photoperiod and temperature conditions. Circadian clock is involved in the
      temperature adaptive photoperiodic control of plant architecture, including
      hypocotyl elongation in Arabidopsis thaliana. In this regulation, phytochrome
      interacting transcriptional factors, PIF4 and PIF5, are activated at the end of
      night under short photoperiod or high temperature conditions, due to the
      coincidence between internal (circadian rhythm of the transcripts) and external
      (length of dark period) time cues. It is previously found that biosynthesis or
      metabolism of phytohormones including auxin, and their signal transduction
      related genes are downstream targets of circadian clock and PIF4/PIF5 mediated
      external coincidence mechanism. Brassinosteroid and gibberellic acid played a
      positive role in the hypocotyl elongation of seedlings under light and dark cycle
      conditions. On the other hand, cytokinin and jasmonic acid played an opposite
      role. In this study, diurnal expression profile of a gene encoding a
      sulfotransferase family protein that is involved in the jasmonic acid metabolism,
      ST2A, was examined. It was found that transcription of ST2A is induced at the end
      of night under LD/22  degrees C and SD/28  degrees C conditions according to the
      external coincidence mechanism. The results of this study support the idea that
      the circadian clock orchestrates a variety of hormone-signaling pathways to
      regulate the photoperiod and temperature-dependent morphogenesis in A. thaliana.

PMID- 24317065
TI  - Maillard reaction inhibitors produced by Paecilomyces sp.
AB  - Maillard reaction inhibitors could be useful therapeutics for diabetes and other
      age-related diseases. We isolated for the first time 4-O-demethylsilvaticol (1)
      and (-)-mitorubrin (2) as Maillard reaction inhibitors from Paecilomyces sp.
      3193B. Among the isolated inhibitors, 2 showed most potent inhibitory effect by
      an SDS-PAGE assay on cross-linked protein formation and by a fluorescent assay on
      AGE formation. 

PMID- 24317066
TI  - Expression and characterization of a thermostable acetylxylan esterase from
      Caldanaerobacter subterraneus subsp. tengcongensis involved in the degradation of
      insoluble cellulose acetate.
AB  - A thermostable acetylxylan esterase gene, TTE0866, which catalyzes the
      deacetylation of cellulose acetate, was cloned from the genome of
      Caldanaerobacter subterraneus subsp. tengcongensis. The pH and temperature optima
      were 8.0 and 60  degrees C. The esterase was inhibited by phenylmethylsulfonyl
      fluoride. A mixture of the esterase and cellulolytic enzymes efficiently degraded
      insoluble cellulose acetate with a higher degree of substitution. 

PMID- 24317067
TI  - Protease-deficient Saccharomyces cerevisiae strains for the synthesis of human
      compatible glycoproteins.
AB  - Saccharomyces cerevisiae strains engineered previously to produce proteins with
      mammalian high mannose structures showed severe growth defects and decreased
      protein productivity. In strain YAB101, derived from one of these strains by a
      mutagenesis technique based on the disparity theory of evolution, these
      undesirable phenotypes were alleviated. Here we describe further engineering of
      YAB101 with the aim of synthesizing heterologous glycoproteins with Man5GlcNAc2,
      an intermediate for the mammalian hybrid and complex type oligosaccharides. About
      60% conversion of Man8GlcNAc2 to Man5GlcNAc2 was observed after integration of
      Aspergillus saitoi alpha-1,2-mannosidase fused to the transmembrane domain of S.
      cerevisiae Och1. To obtain a higher yield of the target protein, a protease
      deficient version of this strain was generated by disruption of PEP4 and PRB1,
      resulting in YAB101-4. Inactivation of these vacuolar proteases enhanced the
      secretion of human interferon-beta by approximately 10-fold. 

PMID- 24317068
TI  - Deciphering the roles of glycan processing in glycoprotein quality control
      through organic synthesis.
AB  - Protein quality control (QC) in the endoplasmic reticulum (ER) comprises many
      aspects, including folding and transport of nascent proteins and degradation of
      misfolded proteins. Recent studies have revealed that high-mannose-type glycans
      play pivotal roles in the QC process. To gain knowledge of the molecular basis of
      this process with well-defined homogeneous compounds, we achieved a convergent
      synthesis of high-mannose-type glycans and their functionalized derivatives. A
      major part of our study focused on analyses of UDP-Glc: glycoprotein
      glucosyltransferase (UGGT) and ER glucosidase II, which play crucial roles in
      glycoprotein QC, to clarify their specificities. In addition, we established an
      in vitro assay system mimicking the in vivo condition, which is highly crowded
      due to the presence of various macromolecules. 

PMID- 24317069
TI  - Identification and characterization of a gene encoding an ABC transporter
      expressed in the dicarboxylic acid-producing yeast Candida maltosa.
AB  - A gene, CmCDR1, encoding an ABC transporter of the dicarboxylic acid (DCA)
      producing yeast Candida maltosa was cloned. Transcription of CmCDR1 was
      upregulated in a DCA-hyper-producing mutant of C. maltosa in a later phase of
      culture on n-dodecane, but not in its parental strain. CmCDR1 expression was
      significantly induced by the longer-chain DCA in this mutant. 

PMID- 24317070
TI  - Heterologous production of desferrioxamines with a fusion biosynthetic gene
      cluster.
AB  - Desferrioxamines E (1), D2 (2), X1 (3), and X2 (4), four macrocyclic N-hydroxy-N
      succinyl diamine-based siderophores, were produced efficiently by heterologous
      expression of a fusion biosynthetic gene cluster. This expression system
      consisted of three genes (mbsA-C) from marine metagenomic DNA and one gene
      (dfoC(C)) from the terrestrial bacterium Erwinia amylovora. The first three genes
      are functional in the production of the common monomers N-hydroxy-N-succinyl
      cadaverine (5, HSC) and N-hydroxy-N-succinyl putrescine (6, HSP), whereas dfoC(C)
      catalyzes the oligomerization and the macrocyclization reactions of compounds 5
      and 6 to form compounds 1-4. This fusion gene cluster system provides a
      convenient expression platform for various biosynthetic genes of HSC-HSP based
      siderophores by simply switching the fourth gene by the cassette process. 

PMID- 24317071
TI  - A secondary structure in the 5' untranslated region of adhE mRNA required for
      RNase G-dependent regulation.
AB  - Escherichia coli RNase G is involved in the degradation of several mRNAs,
      including adhE and eno, which encode alcohol dehydrogenase and enolase
      respectively. Previous research indicates that the 5' untranslated region (5'
      UTR) of adhE mRNA gives RNase G-dependency to lacZ mRNA when tagged at the 5'
      end, but it has not been elucidated yet how RNase G recognizes adhE mRNA. Primer
      extension analysis revealed that RNase G cleaved a phosphodiester bond between 
      19A and -18C in the 5'-UTR (the A of the start codon was defined as +1). Site
      directed mutagenesis indicated that RNase G did not recognize the nucleotides at 
      19 and -18. Random deletion analysis indicated that the sequence from -145 to 
      125 was required for RNase G-dependent degradation. Secondary structure
      prediction and further site-directed deletion suggested that the stem-loop
      structure, with a bubble in the stem, is required for RNaseG-dependent
      degradation of adhE mRNA. 

PMID- 24317072
TI  - Isolation of a non-urea-producing sake yeast strain carrying a discriminable
      molecular marker.
AB  - In the fermentation industry, the traceability of microorganisms during the
      process is important to ensure safety and efficacy. Ethyl carbamate, a group-2A
      carcinogen, is produced from ethanol and urea during the storage of
      food/alcoholic beverages. We isolated non-urea-producing sake yeast car1 mutants
      carrying a discriminable molecular marker, and demonstrated, by the use of PCR
      assays, that these mutants are useful for traceability analysis and
      identification during the sake brewing process. 

PMID- 24317073
TI  - Lysophosphatidylcholine potentiates BDNF-induced TrkB phosphorylation and
      downstream signals in cerebellar granule neurons.
AB  - We found that brain-derived neurotrophic factor (BDNF)-induced phosphorylation of
      mitogen-activated protein kinase (MAPK) and Akt in cerebellar granule neurons was
      specifically potentiated by LPC. LPC also augmented the BDNF-induced
      phosphorylation of TrkB, the receptor for BDNF. In TrkB-transfected CHO-K1 cells,
      LPC potentiated BDNF-induced MAPK phosphorylation. These results suggest that LPC
      plays a role in BDNF-TrkB signaling by regulating the activation of TrkB. 

PMID- 24317074
TI  - Mutations in the CCD4 carotenoid cleavage dioxygenase gene of yellow-flesh
      peaches.
AB  - Peach trees bear either white- or yellow-flesh fruit. We found that Japanese
      peach cultivars have two types of mutation in a carotenoid catabolic gene, CCD4:
      the insertion of a retrotransposon, and a frame shift in the microsatellite
      sequences of the first exon. CCD4 in yellow-flesh peaches was disrupted by these
      mutations. 

PMID- 24317075
TI  - MurA as a primary target of tulipalin B and 6-tuliposide B.
AB  - (-)-Tulipalin B and (+)-6-tuliposide B were confirmed to inhibit MurA in vitro.
      However, contrary to fosfomycin, these compounds showed potent inhibitory
      activities against MurA overexpressing Escherichia coli, especially in the
      presence of UDP-GlcNAc. These observations suggest that these compounds induced
      bacterial cell death not through a MurA malfunction, but in such a MurA-mediated
      indirect manner as the inhibition of other Mur enzymes. 

PMID- 24317076
TI  - High salinity alters the germination behavior of Bacillus subtilis spores with
      nutrient and nonnutrient germinants.
AB  - The effect of high NaCl concentrations on nutrient and nonnutrient germination of
      Bacillus subtilis spores was systematically investigated. Under all conditions,
      increasing NaCl concentrations caused increasing, albeit reversible, inhibition
      of germination. High salinity delayed and increased the heterogeneity of
      germination initiation, slowed the germination kinetics of individual spores and
      the whole spore population, and decreased the overall germination efficiency, as
      observed by a variety of different analytical techniques. Germination triggered
      by nutrients which interact with different germinant receptors (GRs) was affected
      differently by NaCl, suggesting that GRs are targets of NaCl inhibition. However,
      NaCl also inhibited GR-independent germination, suggesting that there is at least
      one additional target for NaCl inhibition. Strikingly, a portion of the spore
      population could initiate germination with l-alanine even at NaCl concentrations
      near saturation (~5.4 M), suggesting that spores lack a salt-sensing system
      preventing them from germinating in a hostile high-salinity environment. Spores
      that initiated germination at very high NaCl concentrations excreted their large
      depot of Ca(2+)-pyridine-2,6-dicarboxylic acid and lost their heat resistance,
      but they remained in a phase-gray state in the phase-contrast microscope,
      suggesting that there was incomplete germination. However, some metabolic
      activity could be detected at up to 4.8 M NaCl. Overall, high salinity seems to
      exert complex effects on spore germination and outgrowth whose detailed
      elucidation in future investigations could give valuable insights on these
      processes in general. 

PMID- 24317077
TI  - Kinetics and yields of pesticide biodegradation at low substrate concentrations
      and under conditions restricting assimilable organic carbon.
AB  - The fundamentals of growth-linked biodegradation occurring at low substrate
      concentrations are poorly understood. Substrate utilization kinetics and
      microbial growth yields are two critically important process parameters that can
      be influenced by low substrate concentrations. Standard biodegradation tests
      aimed at measuring these parameters generally ignore the ubiquitous occurrence of
      assimilable organic carbon (AOC) in experimental systems which can be present at
      concentrations exceeding the concentration of the target substrate. The
      occurrence of AOC effectively makes biodegradation assays conducted at low
      substrate concentrations mixed-substrate assays, which can have profound effects
      on observed substrate utilization kinetics and microbial growth yields. In this
      work, we introduce a novel methodology for investigating biodegradation at low
      concentrations by restricting AOC in our experiments. We modified an existing
      method designed to measure trace concentrations of AOC in water samples and
      applied it to systems in which pure bacterial strains were growing on pesticide
      substrates between 0.01 and 50 mg liter(-1). We simultaneously measured substrate
      concentrations by means of high-performance liquid chromatography with UV
      detection (HPLC-UV) or mass spectrometry (MS) and cell densities by means of flow
      cytometry. Our data demonstrate that substrate utilization kinetic parameters
      estimated from high-concentration experiments can be used to predict substrate
      utilization at low concentrations under AOC-restricted conditions. Further,
      restricting AOC in our experiments enabled accurate and direct measurement of
      microbial growth yields at environmentally relevant concentrations for the first
      time. These are critical measurements for evaluating the degradation potential of
      natural or engineered remediation systems. Our work provides novel insights into
      the kinetics of biodegradation processes and growth yields at low substrate
      concentrations. 

PMID- 24317078
TI  - Corrosion of iron by sulfate-reducing bacteria: new views of an old problem.
AB  - About a century ago, researchers first recognized a connection between the
      activity of environmental microorganisms and cases of anaerobic iron corrosion.
      Since then, such microbially influenced corrosion (MIC) has gained prominence and
      its technical and economic implications are now widely recognized. Under anoxic
      conditions (e.g., in oil and gas pipelines), sulfate-reducing bacteria (SRB) are
      commonly considered the main culprits of MIC. This perception largely stems from
      three recurrent observations. First, anoxic sulfate-rich environments (e.g.,
      anoxic seawater) are particularly corrosive. Second, SRB and their characteristic
      corrosion product iron sulfide are ubiquitously associated with anaerobic
      corrosion damage, and third, no other physiological group produces comparably
      severe corrosion damage in laboratory-grown pure cultures. However, there remain
      many open questions as to the underlying mechanisms and their relative
      contributions to corrosion. On the one hand, SRB damage iron constructions
      indirectly through a corrosive chemical agent, hydrogen sulfide, formed by the
      organisms as a dissimilatory product from sulfate reduction with organic
      compounds or hydrogen ("chemical microbially influenced corrosion"; CMIC). On the
      other hand, certain SRB can also attack iron via withdrawal of electrons
      ("electrical microbially influenced corrosion"; EMIC), viz., directly by
      metabolic coupling. Corrosion of iron by SRB is typically associated with the
      formation of iron sulfides (FeS) which, paradoxically, may reduce corrosion in
      some cases while they increase it in others. This brief review traces the
      historical twists in the perception of SRB-induced corrosion, considering the
      presently most plausible explanations as well as possible early misconceptions in
      the understanding of severe corrosion in anoxic, sulfate-rich environments. 

PMID- 24317079
TI  - Carriage of Clostridium difficile by wild urban Norway rats (Rattus norvegicus)
      and black rats (Rattus rattus).
AB  - Clostridium difficile is an important cause of enteric infections in humans.
      Recently, concerns have been raised regarding whether animals could be a source
      of C. difficile spores. Although colonization has been identified in a number of
      domestic species, the ability of commensal pests to serve as a reservoir for C.
      difficile has not been well investigated. The objective of this study was to
      determine whether urban rats (Rattus spp.) from Vancouver, Canada, carry C.
      difficile. Clostridium difficile was isolated from the colon contents of trapped
      rats and was characterized using ribotyping, toxinotyping, and toxin gene
      identification. Generalized linear mixed models and spatial analysis were used to
      characterize the ecology of C. difficile in rats. Clostridium difficile was
      isolated from 95 of 724 (13.1%) rats, although prevalence differed from 0% to
      46.7% among city blocks. The odds of being C. difficile positive decreased with
      increasing weight (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53 to
      0.87), suggesting that carriage is more common in younger animals. The strains
      isolated included 9 ribotypes that matched recognized international designations,
      5 identified by our laboratory in previous studies, and 21 "novel" ribotypes.
      Some strains were clustered geographically; however, the majority were dispersed
      throughout the study area, supporting environmental sources of exposure and
      widespread environmental contamination with a variety of C. difficile strains.
      Given that urban rats are the source of a number of other pathogens responsible
      for human morbidity and mortality, the potential for rats to be a source of C.
      difficile for humans deserves further consideration. 

PMID- 24317080
TI  - Exposure of Escherichia coli ATCC 12806 to sublethal concentrations of food-grade
      biocides influences its ability to form biofilm, resistance to antimicrobials,
      and ultrastructure.
AB  - Escherichia coli ATCC 12806 was exposed to increasing subinhibitory
      concentrations of three biocides widely used in food industry facilities:
      trisodium phosphate (TSP), sodium nitrite (SNI), and sodium hypochlorite (SHY).
      The cultures exhibited an acquired tolerance to biocides (especially to SNI and
      SHY) after exposure to such compounds. E. coli produced biofilms (as observed by
      confocal laser scanning microscopy) on polystyrene microtiter plates. Previous
      adaptation to SNI or SHY enhanced the formation of biofilms (with an increase in
      biovolume and surface coverage) both in the absence and in the presence (MIC/2)
      of such compounds. TSP reduced the ability of E. coli to produce biofilms. The
      concentration of suspended cells in the culture broth in contact with the
      polystyrene surfaces did not influence the biofilm structure. The increase in
      cell surface hydrophobicity (assessed by a test of microbial adhesion to
      solvents) after contact with SNI or SHY appeared to be associated with a strong
      capacity to form biofilms. Cultures exposed to biocides displayed a stable
      reduced susceptibility to a range of antibiotics (mainly aminoglycosides,
      cephalosporins, and quinolones) compared with cultures that were not exposed. SNI
      caused the greatest increase in resistances (14 antibiotics [48.3% of the total
      tested]) compared with TSP (1 antibiotic [3.4%]) and SHY (3 antibiotics [10.3%]).
      Adaptation to SHY involved changes in cell morphology (as observed by scanning
      electron microscopy) and ultrastructure (as observed by transmission electron
      microscopy) which allowed this bacterium to persist in the presence of severe SHY
      challenges. The findings of the present study suggest that the use of biocides at
      subinhibitory concentrations could represent a public health risk. 

PMID- 24317081
TI  - Strain design of Ashbya gossypii for single-cell oil production.
AB  - Single-cell oil (SCO) represents a sustainable alternative for the oil industry.
      Accordingly, the identification of microorganisms with either higher lipidogenic
      ability or novel capacities for the transformation of raw materials constitutes a
      major challenge for the field of oil biotechnology. With this in mind, here, we
      were prompted to address the lipidogenic profile of the filamentous
      hemiascomycete Ashbya gossypii, which is currently used for the microbial
      production of vitamins. We found that A. gossypii mostly accumulates unsaturated
      fatty acids (FAs), with more than 50% of the total FA content corresponding to
      oleic acid. In addition, we engineered A. gossypii strains both lacking the beta
      oxidation pathway and also providing ATP-citrate lyase (ACL) activity to block
      the degradation of FA and to increase the cytosolic acetyl-coenzyme A (CoA)
      content, respectively. The lipidogenic profile of the newly developed strains
      demonstrates that the mere elimination of the beta-oxidation pathway in A.
      gossypii triggers a significant increase in lipid accumulation that can reach 70%
      of cell dry weight. The use of A. gossypii as a novel and robust tool for the
      production of added-value oils is further discussed. 

PMID- 24317082
TI  - Measurement of ice nucleation-active bacteria on plants and in precipitation by
      quantitative PCR.
AB  - Ice nucleation-active (INA) bacteria may function as high-temperature ice
      nucleating particles (INP) in clouds, but their effective contribution to
      atmospheric processes, i.e., their potential to trigger glaciation and
      precipitation, remains uncertain. We know little about their abundance on natural
      vegetation, factors that trigger their release, or persistence of their ice
      nucleation activity once airborne. To facilitate these investigations, we
      developed two quantitative PCR (qPCR) tests of the ina gene to directly count INA
      bacteria in environmental samples. Each of two primer pairs amplified most
      alleles of the ina gene and, taken together, they should amplify all known
      alleles. To aid primer design, we collected many new INA isolates. Alignment of
      their partial ina sequences revealed new and deeply branching clades, including
      sequences from Pseudomonas syringae pv. atropurpurea, Ps. viridiflava, Pantoea
      agglomerans, Xanthomonas campestris, and possibly Ps. putida, Ps. auricularis,
      and Ps. poae. qPCR of leaf washings recorded ~10(8) ina genes g(-1) fresh weight
      of foliage on cereals and 10(5) to 10(7) g(-1) on broadleaf crops. Much lower
      populations were found on most naturally occurring vegetation. In fresh snow, ina
      genes from various INA bacteria were detected in about half the samples but at
      abundances that could have accounted for only a minor proportion of INP at -10
      degrees C (assuming one ina gene per INA bacterium). Despite this, an apparent
      biological source contributed an average of ~85% of INP active at -10 degrees C
      in snow samples. In contrast, a thunderstorm hail sample contained 0.3 INA
      bacteria per INP active at -10 degrees C, suggesting a significant contribution
      to this sample. 

PMID- 24317083
TI  - Mechanism for stabilizing mRNAs involved in methanol-dependent methanogenesis of
      cold-adaptive Methanosarcina mazei zm-15.
AB  - Methylotrophic methanogenesis predominates at low temperatures in the cold Zoige
      wetland in Tibet. To elucidate the basis of cold-adapted methanogenesis in these
      habitats, Methanosarcina mazei zm-15 was isolated, and the molecular basis of its
      cold activity was studied. For this strain, aceticlastic methanogenesis was
      reduced 7.7-fold during growth at 15 degrees C versus 30 degrees C. Methanol
      derived methanogenesis decreased only 3-fold under the same conditions,
      suggesting that it is more cold adaptive. Reverse transcription-quantitative PCR
      (RT-qPCR) detected <2-fold difference in the transcript abundances of mtaA1,
      mtaB1, and mtaC1, the methanol methyltransferase (Mta) genes, in 30 degrees C
      versus 15 degrees C culture, while ackA and pta mRNAs, encoding acetate kinase
      (Ack) and phosphotransacetylase (Pta) in aceticlastic methanogenesis, were 4.5-
      and 6.8-fold higher in 30 degrees C culture than in 15 degrees C culture. The in
      vivo half-lives of mtaA1 and mtaC1B1 mRNAs were similar in 30 degrees C and 15
      degrees C cultures. However, the pta-ackA mRNA half-life was significantly
      reduced in 15 degrees C culture compared to 30 degrees C culture. Using
      circularized RNA RT-PCR, large 5' untranslated regions (UTRs) (270 nucleotides
      [nt] and 238 nt) were identified for mtaA1 and mtaC1B1 mRNAs, while only a 27-nt
      5' UTR was present in the pta-ackA transcript. Removal of the 5' UTRs
      significantly reduced the in vitro half-lives of mtaA1 and mtaC1B1 mRNAs.
      Remarkably, fusion of the mtaA1 or mtaC1B1 5' UTRs to pta-ackA mRNA increased its
      in vitro half-life at both 30 degrees C and 15 degrees C. These results
      demonstrate that the large 5' UTRs significantly enhance the stability of the
      mRNAs involved in methanol-derived methanogenesis in the cold-adaptive M. mazei
      zm-15. 

PMID- 24317085
TI  - Ecology and genetic structure of zoonotic Anisakis spp. from adriatic commercial
      fish species.
AB  - Consumption of raw or thermally inadequately treated fishery products represents
      a public health risk, with the possibility of propagation of live Anisakis
      larvae, the causative agent of the zoonotic disease anisakidosis, or anisakiasis.
      We investigated the population dynamics of Anisakis spp. in commercially
      important fish-anchovies (Anisakis), sardines (Sardina pilchardus), European hake
      (Merluccius merluccius), whiting (Merlangius merlangus), chub mackerel (Scomber
      japonicus), and Atlantic bluefin tuna (Thunnus thynnus)-captured in the main
      Adriatic Sea fishing ground. We observed a significant difference in the numbers
      of parasite larvae (1 to 32) in individual hosts and between species, with most
      fish showing high or very high Anisakis population indices. Phylogenetic analysis
      confirmed that commercial fish in the Adriatic Sea are parasitized by Anisakis
      pegreffii (95.95%) and Anisakis simplex sensu stricto (4.05%). The genetic
      structure of A. pegreffii in demersal, pelagic, and top predator hosts was
      unstructured, and the highest frequency of haplotype sharing (n = 10) was between
      demersal and pelagic fish. 

PMID- 24317086
TI  - Haemodynamic outcome at four-dimensional flow magnetic resonance imaging
      following valve-sparing aortic root replacement with tricuspid and bicuspid valve
      morphology.
AB  - OBJECTIVE: To provide a more complete characterization of aortic blood flow in
      patients following valve-sparing aortic root replacement (VSARR) compared with
      presurgical cohorts matched by tricuspid and bicuspid valve morphology, age and
      presurgical aorta size. METHODS: Four-dimensional (4D) flow magnetic resonance
      imaging (MRI) was performed to analyse three-dimensional (3D) blood flow in the
      thoracic aorta of n = 13 patients after VSARR with reimplantation of native
      tricuspid aortic valve (TAV, n = 6) and bicuspid aortic valve (BAV, n = 7).
      Results were compared with presurgical age and aortic size-matched control
      cohorts with TAV (n = 10) and BAV (n = 10). Pre- and post-surgical aortic flow
      was evaluated using time-resolved 3D pathlines using a blinded grading system (0
      2, 0 = small, 1 = moderate and 2 = prominent) analysing ascending aortic (AAo)
      helical flow. Systolic flow profile uniformity in the aortic root, proximal and
      mid-AAo was evaluated using a four-quadrant model. Further analysis in nine
      analysis planes distributed along the thoracic aorta quantified peak systolic
      velocity, retrograde fraction and peak systolic flow acceleration. RESULTS:
      Pronounced AAo helical flow in presurgical control subjects (both BAV and TAV:
      helix grading = 1.8 +/- 0.4) was significantly reduced (0.2 +/- 0.4, P < 0.001)
      in cohorts after VSARR independent of aortic valve morphology. Presurgical AAo
      flow was highly eccentric for BAV patients but more uniform for TAV. VSARR
      resulted in less eccentric flow profiles. Systolic peak velocities were
      significantly (P < 0.05) increased in post-root repair BAV patients throughout
      the aorta (six of nine analysis planes) and to a lesser extent in TAV patients
      (three of nine analysis planes). BAV reimplantation resulted in significantly
      increased peak velocities in the proximal AAo compared with root repair with TAV
      (2.3 +/- 0.6 vs 1.6 +/- 0.4 m/s, P = 0.017). Post-surgical patients showed a non
      significant trend towards higher systolic flow acceleration as a surrogate
      measure of reduced aortic compliance. CONCLUSIONS: VSARR restored a cohesive flow
      pattern independent of native valve morphology but resulted in increased peak
      velocities throughout the aorta. 4D flow MRI methods can assess the clinical
      implications of altered aortic flow dynamics in patients undergoing VSARR.

PMID- 24317087
TI  - Robot-assisted thyroidectomy with novel camera-port retractor.
AB  - We performed gasless transaxillary robot-assisted thyroidectomy with a novel
      camera-port retractor (CP retractor). Herein, we describe the new instrument and
      its efficacy, which was evaluated by performing robot-assisted thyroidectomy.
      From October 2009 to August 2012, a total of 12 patients underwent robot-assisted
      thyroidectomy using the da Vinci Surgical System. The CP retractor was used in
      all cases, and we use the Maryland bipolar forceps and the microbipolar forceps
      on both arms for dissection of the surrounding tissues as well as for cutting and
      coagulation to avoid injury to the vessels and the nerves. The CP retractor
      provided excellent visualization without robotic arm instrument interference. The
      novel retractor is useful and safe, and the use of bipolar instruments is an
      effective option for robotic dissection around the nerves in the robot-assisted
      thyroidectomy. 

PMID- 24317088
TI  - Off-pump total arterial revascularization in the absence of the left main
      coronary artery.

PMID- 24317089
TI  - Targeting HSP90 and monoclonal protein trafficking modulates the unfolded protein
      response, chaperone regulation and apoptosis in myeloma cells.
AB  - Multiple myeloma is characterized by the production of substantial quantities of
      monoclonal protein. We have previously demonstrated that select inhibitors of the
      isoprenoid biosynthetic pathway (IBP) induce apoptosis of myeloma cells via
      inhibition of Rab geranylgeranylation, leading to disruption of monoclonal
      protein trafficking and induction of the unfolded protein response (UPR) pathway.
      Heat-shock protein 90 (HSP90) inhibitors disrupt protein folding and are
      currently under clinical investigation in myeloma. The effects of combining IBP
      and HSP90 inhibitors on cell death, monoclonal protein trafficking, the UPR and
      chaperone regulation were investigated in monoclonal protein-producing cells. An
      enhanced induction of cell death was observed following treatment with IBP and
      HSP90 inhibitors, which occurred through both ER stress and non-ER stress
      pathways. The HSP90 inhibitor 17-AAG abrogated the effects of the IBP inhibitors
      on intracellular monoclonal protein levels and localization as well as induction
      of the UPR in myeloma cells. Disparate effects on chaperone expression were
      observed in myeloma vs amyloid light chain cells. Here we demonstrate that the
      novel strategy of targeting MP trafficking in concert with HSP90 enhances myeloma
      cell death via a complex modulation of ER stress, UPR, and cell death pathways. 

PMID- 24317091
TI  - Antiepileptic treatment for anti-NMDA receptor encephalitis: the need for video
      EEG monitoring.

PMID- 24317090
TI  - Novel somatic mutations in large granular lymphocytic leukemia affecting the STAT
      pathway and T-cell activation.
AB  - T-cell large granular lymphocytic (T-LGL) leukemia is a clonal disease
      characterized by the expansion of mature CD3+CD8+ cytotoxic T cells. It is often
      associated with autoimmune disorders and immune-mediated cytopenias. Our recent
      findings suggest that up to 40% of T-LGL patients harbor mutations in the STAT3
      gene, whereas STAT5 mutations are present in 2% of patients. In order to identify
      putative disease-causing genetic alterations in the remaining T-LGL patients, we
      performed exome sequencing from three STAT mutation-negative patients and
      validated the findings in 113 large granular lymphocytic (LGL) leukemia patients.
      On average, 11 CD8+ LGL leukemia cell-specific high-confidence nonsynonymous
      somatic mutations were discovered in each patient. Interestingly, all patients
      had at least one mutation that affects either directly the STAT3-pathway (such as
      PTPRT) or T-cell activation (BCL11B, SLIT2 and NRP1). In all three patients, the
      STAT3 pathway was activated when studied by RNA expression or pSTAT3 analysis.
      Screening of the remaining 113 LGL leukemia patients did not reveal additional
      patients with same mutations. These novel mutations are potentially biologically
      relevant and represent rare genetic triggers for T-LGL leukemia, and are
      associated with similar disease phenotype as observed in patients with mutations
      in the STAT3 gene. 

PMID- 24317092
TI  - An on-demand four-way junction DNAzyme nanoswitch driven by inosine-based partial
      strand displacement.
AB  - A DNA four-way junction device capable of junction expansion and contraction
      cycles using an inosine-based partial strand displacement scheme is reported.
      These nanoscale positioning capabilities are used to provide on-demand activation
      and deactivation of a pair of split E6 DNAzymes on the device. The device also
      demonstrates a combined catalytic rate significantly higher than the original E6
      DNAzyme under similar operational conditions. This approach can provide
      structural organization and spatially control other multicomponent molecular
      complexes. 

PMID- 24317094
TI  - A fluorogenic peptide probe developed by in vitro selection using tRNA carrying a
      fluorogenic amino acid.
AB  - A peptide that binds and emits fluorescence in response to conformational change
      in a target protein was developed by in vitro selection using tRNA carrying a
      fluorogenic amino acid. This technology could prove to be useful for the
      development of separation-free immunoassays and bio-imaging analyses. 

PMID- 24317084
TI  - Replicon-dependent differentiation of symbiosis-related genes in Sinorhizobium
      strains nodulating Glycine max.
AB  - In order to investigate the genetic differentiation of Sinorhizobium strains
      nodulating Glycine max and related microevolutionary mechanisms, three
      housekeeping genes (SMc00019, truA, and thrA) and 16 symbiosis-related genes on
      the chromosome (7 genes), pSymA (6 genes), and pSymB (3 genes) were analyzed.
      Five distinct species were identified among the test strains by calculating the
      average nucleotide identity (ANI) of SMc00019-truA-thrA: Sinorhizobium fredii,
      Sinorhizobium sojae, Sinorhizobium sp. I, Sinorhizobium sp. II, and Sinorhizobium
      sp. III. These species assignments were also supported by population genetics and
      phylogenetic analyses of housekeeping genes and symbiosis-related genes on the
      chromosome and pSymB. Different levels of genetic differentiation were observed
      among these species or different replicons. S. sojae was the most divergent from
      the other test species and was characterized by its low intraspecies diversity
      and limited geographic distribution. Intergenic recombination dominated the
      evolution of 19 genes from different replicons. Intraspecies recombination
      happened frequently in housekeeping genes and symbiosis-related genes on the
      chromosome and pSymB, whereas pSymA genes showed a clear pattern of lateral
      transfer events between different species. Moreover, pSymA genes were
      characterized by a lower level of polymorphism and recombination than those on
      the chromosome and pSymB. Taken together, genes from different replicons of
      rhizobia might be involved in the establishment of symbiosis with legumes, but
      these symbiosis-related genes might have evolved differently according to their
      corresponding replicons. 

PMID- 24317095
TI  - Sudden death due to hydatid cyst: thirty-four medicolegal autopsy cases.
AB  - The natural history of the echinococcosis can be studded with multiple
      complications; the most formidable is sudden death. We studied the
      epidemiological, pathological, and thanatological features of 34 sudden deaths
      due to hydatid cyst. The mean age was 33.2 years. A male predominance was
      observed with a sex ratio of 1.8. Most of our victims were from rural areas
      (79.4%). Sudden death was preceded by prodromal symptoms in 61.7% of cases. The
      most common was dyspnea (23.5%), followed by hemoptysis (11.8%). In 85.3% of
      cases, the cyst location was liver. It was cracked in 25 cases and broken in 6
      cases. The rupture was spontaneous in 25 cases (73%). It was preceded by trauma
      in 7 cases. Death was related to an anaphylactic shock in 82.3% of cases,
      infection in 14.7%, and respiratory distress in 3% of cases. Sudden death is a
      serious and not exceptional complication of hydatid cyst. Several mechanisms may
      explain the sudden death. 

PMID- 24317096
TI  - Immunohistochemical analysis of the ubiquitin proteasome system and autophagy
      lysosome system induced after traumatic intracranial injury: association with
      time between the injury and death.
AB  - This study aimed to analyze how the ubiquitin proteasome system (UPS) or
      autophagy lysosome system (autophagy) are induced in brain tissues at different
      intervals after traumatic intracranial injury in humans. Injured cerebral
      cortices of 36 forensic autopsy cases were analyzed by immunohistochemistry using
      antibodies as the UPS marker (ubiquitin and lysine 48-linked polyubiquitin chains
      [K48]) and autophagy marker (lysine 63-linked polyubiquitin chains [K63],
      p62/sequestome 1 and microtubule-associated protein 1 light chain 3 [LC3]). The
      number of neurons and glial cells with cytoplasmic inclusions that stained
      positive for ubiquitin, K48, and p62 began to increase within 1 hour after
      intracranial injury, particularly at contusion sites. From 3.5 hours onward, an
      increase in cytoplasmic inclusions that stained positive for K63 and LC3 began to
      be detected. LC3-positive cytoplasmic inclusions were not identified after 37
      days; however, the increased immunoreactivity to ubiquitin and anti-K48 antibody
      was maintained for 7 months. These results suggest that the UPS is activated
      earlier and lasts longer than autophagy, that autophagy is activated for a
      relatively short term (between a few hours and approximately 1 month), and that
      the activation occurs especially in severely damaged brain tissues following head
      trauma in humans. 

PMID- 24317097
TI  - A fatal fall associated with undiagnosed parenchymatous neurosyphilis.
AB  - A fall from a great height is often associated with altered mental status. Aside
      from the usual contributing factors, for example, alcohol consumption or mental
      illness, natural disease leading to a fatal fall is seldom identified by autopsy.
      The case described in this report is that of a 57-year-old man who had been
      clinically diagnosed with presenile Alzheimer disease and fell head first into a
      river from the bridge. These events were captured by a surveillance camera on the
      bridge; an acquaintance reported that he had previous suicidal ideation. At
      autopsy, the cervical spinal cord was determined to have been severely injured,
      and the sixth cervical vertebra was observed to have been fractured. Histological
      examination showed chronic meningoencephalitis including neuronal loss,
      perivascular cuffing, and the proliferation of microglia and astrocytes in the
      cerebral cortex. Serologic evaluation consisting of the nontreponemal antigen
      test (rapid plasma reagin [RPR]) and treponemal antibody test (Treponema pallidum
      latex agglutination) was positive in both cases (RPR: 18.2 RPR units, T. pallidum
      latex agglutination: 7718 U/mL). These findings suggested that the patient had
      been affected by a syphilis infection and that his suicidal behavior was
      associated with parenchymatous neurosyphilis. 

PMID- 24317098
TI  - Interobserver variability in the assessment of the clinical severity of
      superficial venous insufficiency.
AB  - BACKGROUND: The clinical class C, of the CEAP classification (Clinical-Etiology
      Anatomy-Pathophysiology), is often used when selecting patients for treatment
      within the national healthcare system. The aim of this study was to test the
      interobserver reproducibility of C when used in a clinical situation where the
      decision for reimbursement was made. METHODS: An unselected series of 78 patients
      (106 limbs) with varicose veins were examined by three independent surgeons with
      regard to C of CEAP and whether there was a medical indication for treatment.
      Interobserver reproducibility was calculated with kappa statistic. RESULTS: Total
      agreement between the three observers for clinical class was obtained in 61% of
      all cases (kappa .55-.68 (95% CI)) and for medical indication in 60% of all cases
      (kappa.35-.57 (95% CI)). CONCLUSION: The reproducibility of C when deciding
      medical indication for treatment is moderate. This may be due to inherent
      difficulties in the CEAP, lack of specific training, or the simultaneous
      assessment of reimbursement that may influence the clinical classification.

PMID- 24317099
TI  - Balloon dacryoplasty in internal ostium stenosis after endoscopic
      dacryocystorhinostomy.
AB  - PURPOSE: To determine the effectiveness of balloon dacryoplasty in the treatment
      of internal ostium stenosis after endoscopic dacryocystorhinostomy (EnDCR).
      METHODS: A retrospective, noncomparative interventional case series of patients
      who underwent balloon dacryoplasty for post-EnDCR internal ostium stenosis were
      included. A balloon catheter was used in all procedures, with bicanalicular
      silicone intubation. Patient records were reviewed and data analyzed. Anatomical
      success was defined by functional endoscopic dye test, and functional success was
      defined as a subjective improvement in symptoms at last follow up. RESULTS:
      Nineteen lacrimal systems of 18 consecutive patients were studied between July
      2007 and September 2012. At a mean follow up of 20 months (range, 3-53 months),
      anatomical success rate was 84% (16/19 systems), whereas functional success was
      74% (14/19 systems). No major complication was observed. CONCLUSIONS: Balloon
      dacryoplasty is a minimally invasive procedure in the treatment of post-EnDCR
      internal ostium stenosis. It is a simple, safe procedure and can provide
      symptomatic relief to some of these patients. It can be considered as a treatment
      option for patients demonstrated with internal ostium stenosis after EnDCR.

PMID- 24317100
TI  - Endovascular preoperative embolization of orbital hemangiopericytoma with n-butyl
      cyanoacrylate glue.
AB  - Hemangiopericytoma is an uncommon neoplasm that may present in myriad locations,
      including the lower extremities, pelvic area, and the head and neck area,
      including the orbit. Orbital hemangiopericytoma is often described as synonymous
      with orbital solitary fibrous tumor, giant cell angiofibroma, and fibrous
      histiocytoma, as they all belong to a spectrum of collagen-rich fibroblastic
      tumors that are often CD34-positive and have overlapping histopathologic
      features. Many cases of orbital hemangiopericytoma have been reported in the
      literature along with various surgical approaches, long-term outcomes, and
      techniques to manage recurrence; however, few have discussed preoperative
      embolization., Intraoperative hemorrhage is a concern in both the congenital and
      the adult form of these cases, and may be an indication for preoperative
      embolization. A unique case of preoperative embolization was presented with n
      butyl cyanoacrylate for surgical resection of a large orbital hemangiopericytoma
      in a 58-year-old woman. 

PMID- 24317101
TI  - An aggressive primary orbital natural killer/T-cell lymphoma case: poor response
      to chemotherapy.
AB  - Natural killer/T-cell lymphoma (NKTCL) and its presentation with extranodal
      orbital involvement as a single lesion are extremely rare. The aim of this
      article was to describe the presentation, diagnosis, and systemic treatment of a
      primary orbital NKTCL. A 67-year-old Caucasian woman presented with left
      exophthalmos, pain, periorbital swelling, and limited extrinsic ocular motility.
      Orbital cellulitis was suspected, but finally orbital biopsy was performed due to
      no response to initial antibiotic and anti-inflammatory standard treatment. The
      pathologic diagnosis was NKTCL. Systemic evaluations were negative. CHOP
      (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy was
      initiated, but after 2 cycles of treatment, tumoral progression was observed.
      SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) rescue
      chemotherapy was then administered. Lymphoma progression was inevitable. She died
      10 months later. Although more nasal NKTCL cases have been described, the
      nonnasal primary orbital NKTCL is an uncommon neoplasm with high mortality rate,
      despite the recent use of more potent chemotherapy regimens. 

PMID- 24317102
TI  - Periorbital ecthyma gangrenosum: a case report and review of the literature.
AB  - Ecthyma gangrenosum is a cutaneous manifestation of a Pseudomonas aeruginosa
      infection that is extremely rare in the periorbital region. The authors present a
      48-year-old woman with a newly diagnosed acute promyelocytic leukemia with
      necrosis of her bilateral upper and lower eyelids and the lacrimal system.
      Following treatment with intravenous antibiotic and surgical debridement with
      delayed reconstruction, the patient had healed well. 

PMID- 24317103
TI  - PROSE scleral lens: a novel aid for staged eyelid reconstruction.
AB  - A 50-year-old man presented with a papillomatous tarsoconjunctival tumor
      involving the medial two-thirds of the left upper eyelid. Office biopsy revealed
      papillary squamous cell carcinoma (SCCA). Rapid tumor growth with caruncular and
      forniceal conjunctival involvement continued, despite a trial of weekly
      interferon-alpha2b intralesional injection therapy. Surgical excision with clear
      margins resulted in a large upper eyelid defect. The suspicion for recurrence
      remained, given the aggressive nature of the tumor. A temporary prosthetic
      replacement of the ocular surface ecosystem (PROSE) scleral lens was fit for
      preservation of the ocular surface and visual function during a 1-month
      observation period. No evidence of recurrence was noted, and the eyelid defect
      was successfully reconstructed with a Cutler-Beard procedure. Local disease was
      controlled; unfortunately, metastatic disease was found in the ipsilateral
      parotid gland 1 year later. Aggressive surgical removal is recommended in
      interferon-alpha2b nonresponsive SCCA tumors. The PROSE scleral contact lens may
      serve as a useful adjunct for the maintenance of a healthy ocular surface and
      visual function during delayed eyelid defect repair. 

PMID- 24317104
TI  - Keloidal scarring in hard palate grafts.
AB  - Hard palate grafts are a commonly accepted treatment for lower eyelid retraction
      and are typically associated with low complication rates. The authors present a
      case of bilateral keloidal scarring within hard palate grafts requiring surgical
      excision. A 72-year-old woman who had undergone bilateral hard palate grafts to
      her lower eyelids for lower eyelid retraction was referred for the evaluation of
      ocular irritation. She was diagnosed with bilateral hypertrophy of the grafts
      with secondary entropion. The grafts were excised; the pathology was consistent
      with keloidal scarring. To the authors' knowledge, there is no previously
      reported case of bilateral keloidal scarring in normal donor tissue, which
      required excision of the hard palate grafts. It is important for oculoplastic
      surgeons to be aware of this potential complication when considering, discussing,
      and consenting patients for eyelid reconstruction with hard palate grafting. 

PMID- 24317105
TI  - A freely movable mucosa-associated lymphoid tissue lymphoma in the preaponeurotic
      space.
AB  - A 70-year-old man presented with a painless, solitary mass in the left upper
      eyelid. The mass moved freely in the whole upper eyelid. MRI revealed a 15*10*5
      mm sized, well-circumscribed mass in the space between the orbital septum and the
      levator aponeurosis. The tumor was removed en bloc via a skin crease approach
      with simultaneous bilateral ptosis repair. The immunohistopathological diagnosis
      was a mucosa-associated lymphoid tissue (MALT) lymphoma. This is the first case
      of a freely movable MALT lymphoma in the preaponeurotic space.

PMID- 24317106
TI  - Case of the weeping wound: formation of a lacrimal pseudocyst following lateral
      canthal surgery.
AB  - An 87-year-old woman presented with a subcutaneous fluid collection overlying the
      right lateral orbital rim 2 days after undergoing a lateral tarsal strip.
      Drainage and excision of fibrinous granulation tissue occurred twice within the
      first postoperative month, with the formation of a lacrimal pseudocyst. The
      pseudocyst repeatedly enlarged following drainage, necessitating 4 needle
      aspirations. A third attempt at excision, coupled with cautery to the wound base,
      and loose wound closure succeeded in breaking the cycle of pseudocyst recurrence.
      However, the wound continued to drain, so aggressive cautery and botulinum toxin
      were used to obliterate the area of presumed lacrimal gland laceration and slow
      tear production. The possibility of damage to the lacrimal system should be
      entertained in the scenario of a postoperative weeping wound. Formation of a
      lacrimal pseudocyst should be considered when a cystic lesion appears following
      surgical intervention in the lateral canthal region. 

PMID- 24317107
TI  - In vivo properties of uterine suspensory tissue in pelvic organ prolapse.
AB  - The uterine suspensory tissue (UST), which includes the cardinal (CL) and
      uterosacral ligaments (USL), plays an important role in resisting pelvic organ
      prolapse (POP). We describe a technique for quantifying the in vivo time
      dependent force-displacement behavior of the UST, demonstrate its feasibility,
      compare data from POP patients to normal subjects previously reported, and use
      the results to identify the properties of the CL and USL via biomechanical
      modeling. Fourteen women with prolapse, without prior surgeries, who were
      scheduled for surgery, were selected from an ongoing study on POP. We developed a
      computer-controlled linear servo actuator, which applied a continuous force and
      simultaneously recorded cervical displacement. Immediately prior to surgery, the
      apparatus was used to apply three "ramp and hold" trials. After a 1.1 N preload
      was applied to remove slack in the UST, a ramp rate of 4 mm/s was used up to a
      maximum force of 17.8 N. Each trial was analyzed and compared with the tissue
      stiffness and energy absorbed during the ramp phase and normalized final force
      during the hold phase. A simplified four-cable model was used to analyze the
      material behavior of each ligament. The mean +/- SD stiffnesses of the UST were
      0.49 +/- 0.13, 0.61 +/- 0.22, and 0.59 +/- 0.2 N/mm from trial 1 to 3, with the
      latter two values differing significantly from the first. The energy absorbed
      significantly decreased from trial 1 (0.27 +/- 0.07) to 2 (0.23 +/- 0.08) and 3
      (0.22 +/- 0.08 J) but not from trial 2 to 3. The normalized final relaxation
      force increased significantly with trial 1. Modeling results for trial 1 showed
      that the stiffnesses of CL and USL were 0.20 +/- 0.06 and 0.12 +/- 0.04 N/mm,
      respectively. Under the maximum load applied in this study, the strain in the CL
      and USL approached about 100%. In the relaxation phase, the peak force decreased
      by 44 +/- 4% after 60 s. A servo actuator apparatus and intraoperative testing
      strategy proved successful in obtaining in vivo time-dependent material
      properties data in representative sample of POP. The UST exhibited visco
      hyperelastic behavior. Unlike a knee ligament, the length of UST could stretch to
      twice their initial length under the maximum force applied in this study. 

PMID- 24317108
TI  - Systematic processes of land use/land cover change to identify relevant driving
      forces: implications on water quality.
AB  - Land use and land cover (LULC) are driving forces that potentially exert
      pressures on water bodies, which are most commonly quantified by simply obtained
      aggregated data. However, this is insufficient to detect the drivers that arise
      from the landscape change itself. To achieve this objective one must distinguish
      between random and systematic transitions and identify the transitions that show
      strong signals of change, since these will make it possible to identify the
      transitions that have evolved due to population growth, industrial expansion
      and/or changes in land management policies. Our goal is to describe a method to
      characterize driving forces both from LULC and dominant LULC changes, recognizing
      that the presence of certain LULC classes as well as the processes of transition
      to other uses are both sources of stress with potential effects on the condition
      of water bodies. This paper first quantifies the driving forces from LULC and
      also from processes of LULC change for three nested regions within the Mondego
      river basin in 1990, 2000 and 2006. It then discusses the implications for the
      environmental water body condition and management policies. The fingerprint left
      on the landscape by some of the dominant changes found, such as urbanization and
      industrial expansion, is, as expected, low due to their proportion in the
      geographic regions under study, yet their magnitude of change and consistency
      reveal strong signals of change regarding the pressures acting in the system.
      Assessing dominant LULC changes is vital for a comprehensive study of driving
      forces with potential impacts on water condition. 

PMID- 24317109
TI  - Clinical significance of Smac and survivin expression in breast cancer patients
      treated with anthracycline-based neoadjuvant chemotherapy.
AB  - The second mitochondria-derived activator of caspases (Smac), an antagonist of
      the inhibitor of apoptosis protein (IAP), increases chemosensitivity in vitro.
      Survivin, an IAP family member, mediates cancer cell survival and
      chemoresistance. The present study investigated the correlation between Smac and
      survivin expression in primary breast cancer, and the sensitivity to
      anthracycline during neoadjuvant chemotherapy (NAC). Pre-treatment biopsies and
      post-anthracycline treatment tumor sections were analyzed from 98 cases.
      Biomarker expression was evaluated by immunohistochemistry in tumor samples from
      clinical stage II and III anthracycline-based NAC-treated breast cancer. A
      univariate analysis indicated that the estrogen receptor (ER), Smac and survivin
      were significantly predictive of a pathological complete response (pCR) (P=0.004,
      0.001 and 0.037, respectively) in pre-chemotherapy samples. ER, Smac and survivin
      expression was also significant for pCR on the multivariate analysis (P=0.001,
      0.031 and 0.012, respectively). An inverse association was identified between
      survivin and Smac expression (r=-0.217, P=0.032; and r=-0.335, P=0.003,
      respectively) prior to and following NAC. The patients with low survivin
      expression or high Smac expression had significantly longer disease-free survival
      (DFS; P=0.012 and P=0.020, respectively) and overall survival (OS; P=0.01 and
      P=0.033, respectively) compared with the patients with high survivin or low Smac
      expression. Cox regression analyses demonstrated that survivin, Smac and clinical
      stage were independent predictors for DFS and OS. The present study indicated the
      significance of Smac and survivin in determining the breast cancer response to
      anthracycline-based chemotherapy, and may permit further stratifying of pre
      chemotherapy patients to undertake more tailored treatments.

PMID- 24317110
TI  - Efficacy of percutaneous balloon aortic valvuloplasty visualized on computed
      tomography.

PMID- 24317112
TI  - The circulation journal in the world.

PMID- 24317111
TI  - Are the site and mode of termination matters of prime importance in catheter
      ablation of persistent atrial fibrillation?

PMID- 24317113
TI  - Remote monitoring leads to early recognition and treatment of critical
      arrhythmias in adults after atrial switch operation for transposition of the
      great arteries.
AB  - BACKGROUND: Adults with transposition of the great arteries (TGA) after atrial
      switch repair have an increased risk for arrhythmia and sudden cardiac death. We
      analyzed whether a remote monitoring (RM) system as part of an implantable
      cardiac device contributes to timely recognition and improved treatment of
      critical arrhythmias in these patients. METHODS AND RESULTS: All consecutive TGA
      patients (n=11) requiring a pacemaker or cardiac resynchronization therapy with
      or without implantable cardioverter defibrillator between 2008 and 2011 were
      included. RM-detected arrhythmia, abnormality of device integrity and reaction
      time from event transmission until acknowledgement via email and clinical
      decision making were analyzed and compared to a control group (n=21). In 10
      patients (91%) 17 arrhythmias were detected, 8 patients (80%) indicated no
      symptoms. In the RM group time interval from transmission to acknowledgement was
      2.4 days (range, 0-4.5 days). Clinical decision-making was advanced by a mean of
      77.5 days (range, 10-197 days) compared with conventional follow-up and
      identified adaption of anti-arrhythmic medication in 8, electrical cardioversion
      in 2, overdrive pacing in 1 and radiofrequency ablation in 2 patients. A coronary
      sinus lead fracture was identified in 1 patient followed by successful
      replacement. CONCLUSIONS:  RM enables early detection of tachyarrhythmia followed
      by optimization of medical treatment and potentially life-saving anti-tachycardic
      intervention in adults after atrial repair of TGA.  

PMID- 24317114
TI  - Gender differences in clinical characteristics, treatment and long-term outcome
      in patients with stage C/D heart failure in Japan. Report from the CHART-2 study.
AB  - BACKGROUND: The gender differences in patients with chronic heart failure (CHF)
      remain to be fully elucidated in the Japanese population. METHODS AND RESULTS: We
      examined gender differences in clinical characteristics, treatment and long-term
      outcome in 4,736 consecutive CHF patients in stage C/D (mean age, 69 years) out
      of 10,219 patients registered in the CHF Registry, named CHART-2 Study (NCT
      00418041). Compared with male patients (68%, n=3,234), female patients (32%,
      n=1,502) were 3.8 years older and had lower prevalence of ischemic heart disease,
      diabetes, smoking, myocardial infarction and cancer. At baseline, women had
      higher prevalence of preserved left ventricular function but had higher NYHA
      functional class and increased brain natriuretic peptide level. In women,
      aspirin, beta-blockers and statins were less frequently used and diuretics were
      more frequently used. Crude mortality rate was similar between the genders during
      the median 3.1-year follow-up (52.4/1,000 and 47.3/1,000 person-years for women
      and men, respectively, P=0.225). On multivariate Cox regression analysis, women
      had a reduced risk of mortality (adjusted HR, 0.791; 95% CI: 0.640-0.979,
      P=0.031). CONCLUSIONS: Substantial gender differences exist in stage C/D CHF
      patients in real-world practice in Japan. Although female CHF patients had better
      survival than male patients after adjustment for baseline differences, crude
      mortality rate was similar between the genders, possibly reflecting relatively
      severer clinical manifestations in women.  

PMID- 24317116
TI  - Leaching of boron, arsenic and selenium from sedimentary rocks: I. Effects of
      contact time, mixing speed and liquid-to-solid ratio.
AB  - Sedimentary rocks of marine origin excavated in tunnel projects were recently
      identified as potentially hazardous because they could release significant
      amounts of toxic trace elements when exposed to the environment. This study
      investigated the leaching characteristics of B, As, Se and the major coexisting
      ions under various conditions to identify the factors and processes controlling
      their evolution in the leachate. In addition, we evaluated whether the parameters
      of the currently used leachability test for excavated rocks were adequate.
      Although the leachabilities of B, As and Se similarly increased at longer contact
      times, only those of B and As were influenced by the mixing speed and/or liquid
      to-solid ratio (L/S). The majority of trace elements dissolved in the leachate
      originated from the dissolution of soluble salts formed from seawater of the
      Cretaceous trapped during the formation of the sedimentary rocks. Moreover, the
      alkaline pH of the leachates could be attributed to the simultaneous dissolutions
      at varying degrees of the mineral components of the rocks as well as the
      precipitation of clay minerals. In the leaching test of excavated rocks for
      regulatory purposes, the best values of contact time and mixing speed should
      represent conditions of the highest trace element extractabilities, which in this
      study were found at longer contact times (>48 h) and the fastest mixing speed
      (200 rpm). The most appropriate L/S for the leaching test is 10 because it was
      around this L/S that the extractabilities and leaching concentrations of the
      trace elements were simultaneously observed at their highest values.

PMID- 24317115
TI  - [Operative treatment of displaced intra-articular calcaneal fractures].
AB  - OBJECTIVE: Anatomic reduction of displaced intra-articular calcaneal fractures
      with restoration of height, length, and axial alignment and reconstruction of the
      subtalar and calcaneocuboid joints. INDICATIONS: Displaced intra-articular
      calcaneal fractures with incongruity of the posterior facet of the subtalar
      joint, loss of height, and axial malalignment. CONTRAINDICATIONS: High
      perioperative risk, soft tissue infection, advanced peripheral arterial disease
      (stage III), neurogenic osteoarthropathy, poor patient compliance (e. g.,
      substance abuse). SURGICAL TECHNIQUE: Extended lateral approach with the patient
      placed on the uninjured side. Reduction of the anatomic shape and joint surfaces
      according to the preoperative CT-based planning. Reduction of the medial wall and
      step-wise reconstruction of the posterior facet from medial to lateral. Reduction
      of the tuberosity and anterior process fragments to the posterior joint block and
      temporary fixation with Kirschner wires. Internal fixation with an anatomic
      lateral plate in a locking or nonlocking mode. Alternatively less invasive
      internal fixation with a calcaneus nail over a sinus tarsi approach for less
      severe fracture types. POSTOPERATIVE MANAGEMENT: The lower leg is immobilized in
      a brace until the wound is healed. Range of motion exercises of the ankle and
      subtalar joints are initiated on the second postoperative day. Patients are
      mobilized in their own shoe with partial weight bearing of 20 kg for 6-12 weeks
      depending on fracture severity and bone quality. RESULTS: Over a 4-year period,
      163 patients with 184 displaced, intra-articular calcaneal fractures were treated
      with a lateral plate via an extended approach. In all, 102 patients with 116
      fractures were followed for a mean of 8 years. A surgical revision was necessary
      in 4 cases (3.4%) of postoperative hematoma, 2 (1.7%) superficial and 5 (4.3%)
      deep infections. Of the latter, 2 patients needed a free flap for definite wound
      coverage, no calcanectomy or amputation was needed. Secondary subtalar fusion for
      symptomatic posttraumatic arthritis was performed in 9 cases (7.8%). At follow
      up, the AOFAS Ankle/Hindfoot Score averaged 70.2, the Zwipp Score averaged 76.0,
      the German versions of the Foot Function Index and SF-36 physical component
      averaged 32.8 and 42.2, respectively. Scores were significantly lower with
      increasing fracture severity according to the Sanders and Zwipp classifications,
      bilateral fractures, open fractures, and with work-related injuries. With less
      invasive fixation using a calcaneal nail, superficial wound edge necrosis was
      seen in 2 of 75 cases (2.7%).

PMID- 24317117
TI  - Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in
      nephrotic syndrome.
AB  - The molecular link between proteinuria and hyperlipidemia in nephrotic syndrome
      is not known. We show in the present study that plasma angiopoietin-like 4
      (Angptl4) links proteinuria with hypertriglyceridemia through two negative
      feedback loops. In previous studies in a rat model that mimics human minimal
      change disease, we observed localized secretion by podocytes of hyposialylated
      Angptl4, a pro-proteinuric form of the protein. But in this study we noted high
      serum levels of Angptl4 (presumably normosialylated based on a neutral
      isoelectric point) in other glomerular diseases as well. Circulating Angptl4 was
      secreted by extrarenal organs in response to an elevated plasma ratio of free
      fatty acids (FFAs) to albumin when proteinuria reached nephrotic range. In a
      systemic feedback loop, these circulating pools of Angptl4 reduced proteinuria by
      interacting with glomerular endothelial alphavbeta5 integrin. Blocking the
      Angptl4-beta5 integrin interaction or global knockout of Angptl4 or beta5
      integrin delayed recovery from peak proteinuria in animal models. But at the same
      time, in a local feedback loop, the elevated extrarenal pools of Angptl4 reduced
      tissue FFA uptake in skeletal muscle, heart and adipose tissue, subsequently
      resulting in hypertriglyceridemia, by inhibiting lipoprotein lipase (LPL)
      mediated hydrolysis of plasma triglycerides to FFAs. Injecting recombinant human
      ANGPTL4 modified at a key LPL interacting site into nephrotic Buffalo Mna and
      Zucker Diabetic Fatty rats reduced proteinuria through the systemic loop but, by
      bypassing the local loop, without increasing plasma triglyceride levels. These
      data show that increases in circulating Angptl4 in response to nephrotic-range
      proteinuria reduces the degree of this pathology, but at the cost of inducing
      hypertriglyceridemia, while also suggesting a possible therapy to treat these
      linked pathologies. 

PMID- 24317118
TI  - Regulatory T cell proliferative potential is impaired in human autoimmune
      disease.
AB  - Human CD4(+)CD25(high)CD127(-)FoxP3(+) regulatory T (Treg) cells suppress immune
      responses in vitro and in vivo. Reduced suppressive function and/or number of
      peripheral Treg cells has been previously reported in autoimmune disorders. Treg
      cells represent the most actively replicating compartment within the CD4(+) cells
      in vivo, but they are hyporesponsive to classical T cell receptor (TCR)
      stimulation in vitro, a condition that is secondary to their overactive metabolic
      state. Here we report that proliferation of Treg cells after TCR stimulation is
      impaired in subjects with relapsing-remitting multiple sclerosis (RRMS) because
      of altered interleukin-2 (IL-2) secretion and IL-2 receptor (IL-2R)-signal
      transducer and activator of transcription 5 (STAT5) signaling. This is associated
      with decreased expression of the forkhead box P3 (FoxP3) 44- and 47-kDa splicing
      forms, overactivation of S6 ribosomal protein (a downstream target of the
      mammalian target of rapamycin, mTOR) and altered activity of the cyclin-dependent
      kinase inhibitor p27 (p27(kip1)) and extracellular signal-related kinases 1 and 2
      (ERK1/2). The impaired capacity of Treg cells to proliferate in RRMS correlates
      with the clinical state of the subject, where increasing disease severity is
      associated with a decline in Treg cell expansion. These results suggest a
      previously unrecognized mechanism that may account for the progressive loss of
      Treg cells in autoimmune disease. 

PMID- 24317119
TI  - Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled
      glucose.
AB  - In this study, we monitored glycolysis in mouse lymphoma and lung tumors by
      measuring the conversion of hyperpolarized [U-2H, U-13C]glucose to lactate using
      13C magnetic resonance spectroscopy and spectroscopic imaging. We observed
      labeled lactate only in tumors and not in surrounding normal tissue or other
      tissues in the body and found that it was markedly decreased at 24 h after
      treatment with a chemotherapeutic drug. We also detected an increase in a
      resonance assigned to 6-phosphogluconate in the pentose phosphate pathway. This
      technique could provide a new way of detecting early evidence of tumor treatment
      response in the clinic and of monitoring tumor pentose phosphate pathway
      activity. 

PMID- 24317120
TI  - Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in
      humans using dynamic 13C magnetic resonance spectroscopy.
AB  - Despite the central role of the liver in the regulation of glucose and lipid
      metabolism, there are currently no methods to directly assess hepatic oxidative
      metabolism in humans in vivo. By using a new (13)C-labeling strategy in
      combination with (13)C magnetic resonance spectroscopy, we show that rates of
      mitochondrial oxidation and anaplerosis in human liver can be directly determined
      noninvasively. Using this approach, we found the mean rates of hepatic
      tricarboxylic acid (TCA) cycle flux (VTCA) and anaplerotic flux (VANA) to be 0.43
      +/- 0.04 MUmol g(-1) min(-1) and 0.60 +/- 0.11 MUmol g(-1) min(-1), respectively,
      in twelve healthy, lean individuals. We also found the VANA/VTCA ratio to be 1.39
      +/- 0.22, which is severalfold lower than recently published estimates using an
      indirect approach. This method will be useful for understanding the pathogenesis
      of nonalcoholic fatty liver disease and type 2 diabetes, as well as for assessing
      the effectiveness of new therapies targeting these pathways in humans. 

PMID- 24317121
TI  - A method for handling intensity inhomogenieties in fMRI sequences of moving
      anatomy of the early developing brain.
AB  - This paper presents a method for intensity inhomogeniety removal in fMRI studies
      of a moving subject. In such studies, subtle changes in signal as the subject
      moves in the presence of a bias field can be a significant confound for BOLD
      signal analysis. The proposed method avoids the need for a specific tissue model
      or assumptions about tissue homogeneity by making use of the multiple views of
      the underlying bias field provided by the subject's motion. A parametric bias
      field model is assumed and a regression model is used to estimate the basis
      function weights of this model. Quantitative evaluation of the effects of motion
      and noise in motion estimates are performed using simulated data. Results
      demonstrate the strength and robustness of the new method compared to the state
      of the art 4D nonparametric bias estimator (N4ITK). We also qualitatively
      demonstrate the impact of the method on resting state neuroimage analysis of a
      moving adult brain with simulated motion and bias fields, as well as on in vivo
      moving fetal fMRI. 

PMID- 24317122
TI  - Efficacy of exercise training in SCT patients--who benefits most?
AB  - Patients undergoing allo-HCT often experience a substantial loss in physical
      performance. We have recently published the general effectiveness of an exercise
      intervention in 105 allo-HCT patients on physical performance and psychosocial
      well-being. However, predictor variables for differentiated treatment response
      remained unclear. To determine the impact of basic physical performance on
      treatment response, we assessed muscle strength and endurance performance at four
      assessment points before and after allo-HCT. The exercise group started training
      2 weeks before admission and ended 6-8 weeks after discharge. Comparing initially
      fit with unfit classified patients, the fit patients lost 31% of the strength of
      the knee-extensors, whereas the unfit patients lost only 1% (P<0.05). For
      endurance capacity, fit patients lost 4% of their walking capability, whereas
      unfit patients gained 13% (P<0.05). The individual percent change was
      statistically different at the 0.05 level in all measures of physical
      performance. Individual training response in allo-HCT patients strongly depends
      on the initial physical performance level. Unfit patients can be trained safely
      and may benefit more from this exercise intervention than fit patients. This
      result is of major clinical relevance and should encourage hematologists to
      promote exercise even more in impaired/unfit allo-HCT patients. 

PMID- 24317123
TI  - Urinary cytokines after HCT: evidence for renal inflammation in the pathogenesis
      of proteinuria and kidney disease.
AB  - We compared urinary levels of cytokines in patients with and without albuminuria,
      proteinuria and kidney disease (glomerular filtration rate<60 mL/min per 1.73
      m(2)) after HCT. Plasma and urine were collected at baseline and weekly through
      day 100 and monthly through year 1, for measurement of IL-6, gp130, sIL6r, IL-10,
      IL15, MCP-1 and urine albumin-to-creatinine ratios (ACRs). Cox-proportional
      hazards modeling examined associations between urinary cytokine levels and
      development of these renal end points. The association of ACR with the hazard of
      overall mortality was assessed using Cox regression. Increasing urinary IL-6 and
      IL-15 were associated with an increased risk of developing proteinuria. Urinary
      MCP-1 during the first 100 days post HCT was associated with kidney disease at 1
      year. The degree of albuminuria at any time point in the first 100 days post
      transplant was related to the subsequent risk of death (for ACR 30-299, hazard
      ratio (HR)=1.91; 95% confidence interval (CI): 1.27-2.87; for ACR >300, HR=2.82;
      95% CI: 1.60-4.98). After HCT, elevated urinary levels of pro-inflammatory
      cytokines are associated with development of albuminuria and proteinuria,
      suggesting early intra-renal inflammation as an important pathogenetic mechanism.
      Albuminuria and proteinuria within the first 100 days post HCT are associated
      with decreased overall survival. 

PMID- 24317124
TI  - Targeted Busulfan therapy with a steady-state concentration of 600-700 ng/mL in
      patients with sickle cell disease receiving HLA-identical sibling bone marrow
      transplant.
AB  - Busulfan (BU) has a narrow therapeutic window and the average concentration of BU
      at steady state (Css) is critical for successful engraftment in children
      receiving BU as part of the preparative regimen for allogeneic transplants.
      Sixteen patients with sickle cell disease (SCD) underwent allogeneic bone marrow
      transplant (BMT) from HLA-identical siblings. The preparative regimen consisted
      of intravenous BU 0.8-1 mg/kg/dose for 16 doses, cytoxan (CY) of 50 mg/kg daily
      for four doses and equine anti-thymocyte globulin (ATG) 30 mg/kg daily for three
      doses. BU levels were adjusted to provide a total exposure Css of 600-700 ng/mL.
      The median age at the time of transplant was 6.2 years (range 1.2-19.3). Fourteen
      (87%) patients required adjustment of the BU dose to achieve a median Css of 652
      ng/mL (range 607-700). All patients achieved neutrophil and platelet engraftment
      without significant toxicity. Median donor engraftment at the last follow-up was
      100% (range 80-100). None of the patients experienced sickle cell-related
      complications post transplant. With a median follow-up of 3 years (range 1.3-9),
      the event-free survival (EFS) and overall survival (OS) are both 100%. We
      conclude that targeting of BU Css between 600 and 700 ng/mL in this regimen can
      result in excellent and sustained engraftment in young patients with SCD. 

PMID- 24317125
TI  - Value of novel agents and intensive therapy for patients with multiple myeloma.
AB  - We conducted a retrospective evaluation of response and survival for 293 patients
      with multiple myeloma treated since June 2000 with primary thalidomide- or
      bortezomib-based combinations, of whom 207 patients received intensive therapy
      supported by autologous blood stem cells within the first year. Survival times
      were calculated after a landmark of 1 year from start of therapy, so that
      subsequent median survival was 8.9 years for patients with CR, 4.9 years for
      those with PR and 0.6 year for patients with NR (P<0.001). Multivariate analyses
      confirmed CR or PR as the major favorable factors with less impact on prognosis
      for age or disease stage. Both novel agents and high-dose therapy (HDT) resulted
      in high frequencies of PR or CR, with early HDT useful for many patients with NR
      or PR in improving response status and subsequent survival. 

PMID- 24317126
TI  - A clofarabine-based bridging regimen in patients with relapsed ALL and persistent
      minimal residual disease (MRD).
AB  - In patients with relapsed ALL, minimal residual disease (MRD) identified prior to
      allogeneic hematopoietic cell transplantation (HCT) is a strong predictor of
      relapse. We report our experience using a combination of reduced-dosing
      clofarabine, CY and etoposide as a 'bridge' to HCT in eight patients with high
      risk or relapsed ALL and pre-HCT MRD. All patients had detectable MRD (>0.01%,
      flow cytometry) at the start of therapy with all eight achieving MRD reduction
      following one cycle. The regimen was well tolerated with seven grade 3/4
      toxicities occurring among four of the eight patients. Five patients (62.5%) are
      alive, one died from relapse (12.5%) and two from transplant-related mortality
      (25%). The combination of reduced-dose clofarabine, CY and etoposide as bridging
      therapy appears to be well tolerated in patients with relapsed ALL and is
      effective in reducing pre-HCT MRD. 

PMID- 24317127
TI  - Plerixafor 'on demand': results of a strategy based on peripheral blood CD34+
      cells in lymphoma patients at first or subsequent mobilization with
      chemotherapy+G-CSF.

PMID- 24317128
TI  - Minor RBC Ab and allo-SCT.

PMID- 24317129
TI  - Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL
      amyloidosis and cardiac involvement.
AB  - In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse
      prognosis and increased treatment-related complications. In this retrospective
      cohort study, we assessed survival, hematologic and cardiac responses to high
      dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac
      involvement, stratified by cardiac biomarkers brain natriuretic peptide and
      Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent
      HDM/SCT based upon functional measures; six patients had modified cardiac stage I
      disease, seventeen had modified cardiac stage II disease and twenty-four had
      modified cardiac stage III disease. Treatment-related mortality was 4% for all
      patients and 8% for patients with stage III disease. Three-year survival was 88%
      and EFS was 47%; these did not differ by stage. By intention-to-treat analysis,
      27% of patients achieved a hematologic complete response and 32% a very good
      partial response, of whom 70 and 45%, respectively, have not required additional
      therapy at 36 months. Cardiac response was achieved in 53% of patients. We
      conclude that with appropriate patient selection and a risk-adapted treatment
      approach, HDM/SCT is safe and effective in patients with AL amyloidosis and
      cardiac involvement. 

PMID- 24317130
TI  - Significant improvement of Takayasu arteritis after cord blood transplantation in
      a patient with myelodysplastic syndrome.

PMID- 24317132
TI  - Palladium nanosheets as highly stable and effective contrast agents for in vivo
      photoacoustic molecular imaging.
AB  - A stable and efficient contrast agent is highly desirable for photoacoustic (PA)
      imaging applications. Recently gold nanostructures have been widely reported and
      studied for PA imaging and photothermal therapy. However, the structures of the
      nonspherical gold nanoparticles are easily destroyed after laser irradiation and
      thus may fail to complete the intended tasks. In this study, we propose to apply
      palladium nanosheets (PNSs), with strong optical absorption in the near-infrared
      (NIR) region, as a new class of exogenous PA contrast agents. PA and ultrasound
      (US) images were acquired sequentially by a portable and fast photoacoustic
      tomography (PAT) system with a hand-held transducer. Significant and long-lasting
      imaging enhancement in SCC7 head and neck squamous cell carcinoma was
      successfully observed in mice by PAT over time after tail vein administration of
      PNSs. The morphology and functional perfusion of the tumors were delineated in PA
      images due to the nanoparticle accumulation. PAT of the main organs was also
      conducted ex vivo to trace the fate of PNSs, which was further validated by
      inductively coupled plasma atomic emission spectrometry (ICP-AES). No obvious
      toxic effect was observed by in vitro MTT assay and ex vivo histological
      examination 7 days after PNS administration. With the combination of a portable
      imaging instrument and signal specificity, PNSs might be applied as stable and
      effective agents for photoacoustic cancer detection, diagnosis and treatment
      guidance. 

PMID- 24317131
TI  - Impact on long-term OS of conditioning regimen in allogeneic BMT for children
      with AML in first CR: TBI+CY versus BU+CY: a report from the Societe Francaise de
      Greffe de Moelle et de Therapie Cellulaire.
AB  - Allogeneic hematopoietic SCT (HSCT) appears to be an efficient tool to cure high
      risk AML in first CR but the choice between BU-based or TBI-based conditioning
      regimens still remains controversial. In order to analyze the impact of
      conditioning regimen on long-term survival, we conducted a retrospective analysis
      from French registry data including all consecutive patients under 18 years old
      (n=226) from 1980 to 2004 transplanted for AML in CR1 from sibling (n=142) or
      matched unrelated donors and given either TBI-1200 cGy and CY 120 mg/kg (TBI-Cy,
      n=84) or BU 16 mg/kg and CY 200 mg/kg (BuCy200, n=142). Patient subgroups were
      comparable for all criteria except for median age at diagnosis and HSCT and for
      donor type. Both 5-year OS and disease-free survival (DFS) were significantly
      better in BuCy200 group (P=0.02 and 0.005, respectively). In multivariate
      analysis, both HLA matching and BuCy200 appeared as good prognostic factors for
      treatment-related mortality and DFS. Grade 2-4 acute GvHD and chronic GvHD rates
      were statistically higher in TBI-Cy group than in Bu-Cy200 one with a RR at 2
      (P=0.002). In total, Bu-Cy200 conditioning regimen gives better outcome compared
      with TBI-Cy irrespective of the stem cell source and the donor type. 

PMID- 24317133
TI  - Extreme delta brush in a patient with anti-NMDAR encephalitis.
AB  - Anti-N-methyl-D-aspartate receptor encephalitis is a severe, potentially
      treatable, disorder and prognosis depends on early recognition and prompt
      immunotherapy. We report a case of anti-N-methyl-D-aspartate receptor
      encephalitis with atypical age and gender, and a characteristic
      electroencephalographic pattern that supported the diagnosis. A 66-year-old male
      presented with psychiatric disturbances and focal seizures with alteration of
      consciousness, and progressed to a state of akinetic mutism. Auxiliary tests were
      negative or non-specific for anti-NMDAR encephalitis. Electroencephalographic
      monitoring revealed a unique pattern; the extreme delta brush. The patient
      improved with immunotherapy and was asymptomatic at six months of follow-up.
      Ancillary testing was positive for anti-N-methyl-D-aspartate receptor antibodies.
      Extreme delta brush is a recently described electroencephalographic pattern
      presenting in only one third of patients with anti-N-methyl-D-aspartate receptor
      encephalitis. The identification of this pattern, as in our case, may guide early
      diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis. 

PMID- 24317134
TI  - Factors in contact lens symptoms: evidence from a multistudy database.
AB  - PURPOSE: This study aimed to examine the effects of demographic, lens
      performance, and ocular surface response measures on contact lens-related
      discomfort and dryness, using a large contact lens study database. METHODS: A
      total of 4164 records were extracted from a database of 220 subjects
      participating in 46 silicone hydrogel contact lens studies. Subjects discontinued
      lens wear for 24 hours and were then fit with either comfilcon A or enfilcon A
      lenses. The fit and performance of the lenses, along with subjective comfort and
      dryness, were assessed on insertion and after 3 and 6 hours of wear. After 6
      hours of wear, ocular surface health was also assessed by fluorescein slitlamp
      examination. RESULTS: Decreased comfort at 3 hours after insertion was associated
      with excessive lens movement (p < 0.001), front surface deposits (p = 0.004),
      poor wettability (p = 0.014), and Asian ethnicity (p < 0.001). After 6 hours of
      wear, decreased comfort remained associated with greater lens movement (p =
      0.032) and Asian ethnicity (p < 0.001), along with inferior corneal staining (p <
      0.001). Dryness after 3 hours of wear was associated with greater lens movement
      (p < 0.001), Asian ethnicity (p < 0.001), increased deposits (p < 0.001), and
      poor wettability (p < 0.001). Dryness after 6 hours of wear remained associated
      with greater lens movement (p < 0.001) and Asian ethnicity (p < 0.001), along
      with inferior corneal staining (p < 0.001) and inferior lens decentration (p =
      0.001). CONCLUSIONS: Excessive lens movement, inferior lens decentration, poor
      surface wettability and deposits, inferior corneal staining, and Asian ethnicity
      are associated with discomfort and dryness. Clinicians should consider all these
      factors to achieve the most comfortable and successful contact lens fit.

PMID- 24317135
TI  - Correlation of tear osmolarity and dry eye symptoms in convention attendees.
AB  - PURPOSE: To assess the correlation between tear osmolarity readings and symptoms
      of dry eye in a nonclinical convenience sample and to determine how well symptoms
      and osmolarity correlate with the self-assessment of dry eye. METHODS: Two
      hundred forty-nine attendees in the exhibit hall at an optometric educational
      meeting agreed to participate in a dry eye study. Contact lens wearers were
      excluded. Volunteers supplied demographic information and completed a 5-item Dry
      Eye Questionnaire (DEQ-5) and answered the question "Do you think you have dry
      eye" with a yes or no response. Osmolarity testing was done using the TearLab
      instrument on the right eye, then on the left eye. Pearson correlation analyses
      were performed to determine the relationship between variables. RESULTS: There
      was no correlation between DEQ-5 scores and average tear osmolarity (correlation
      coefficient, 0.02) and highest osmolarity (correlation coefficient, 0.03). The
      mean DEQ-5 score was significantly higher among subjects who self-reported dry
      eye (mean, 11.3; p < 0.0001) compared with those who did not (mean, 5.4; p <
      0.0001). No differences were observed between the yes and no self-reported dry
      eye groups and average osmolarity (p = 0.23) and highest osmolarity (p = 0.14).
      CONCLUSIONS: In this nonclinical population, there was no significant correlation
      between tear osmolarity and ocular symptoms as reported or between tear
      osmolarity and the self-assessment of dry eye.

PMID- 24317136
TI  - Neural constraints on visual acuity in proliferative diabetic retinopathy.
AB  - PURPOSE: Visual acuity (VA) in normally sighted individuals is highly correlated
      with equivalent intrinsic blur, a measure of the amount of blur within the visual
      system that is generated by optical and neural sources. This study assessed the
      extent to which VA, equivalent intrinsic blur, optical blur, and neural blur are
      abnormal in subjects with proliferative diabetic retinopathy (PDR) and
      characterized the relationships among these parameters. METHODS: Best-corrected
      VA of 10 subjects with PDR (ages 25 to 68) and 10 normally sighted individuals
      (ages 46 to 63) was measured for tumbling E optotypes. The Es were either
      unblurred or blurred through convolution with Gaussian functions of different
      widths. Values of equivalent intrinsic blur (sigma(int)) and unblurred VA (MAR0)
      were derived using a standard model. Optical blur (sigma(opt)), a measure of blur
      generated by higher-order aberrations, was quantified using Shack-Hartmann
      aberrometry. An index of neural blur (eta) was defined as 1-
      sigma(opt)/sigma(int), which represents the remaining blur once the contributions
      of sigma(opt) to sigma(int) have been accounted for. RESULTS: Log MAR0 and log
      sigma(int) were correlated significantly (r = 0.98, p < 0.05) for the PDR
      subjects and the values of these parameters ranged from normal to more than a
      factor of 2 above the upper limit of normal. In comparison, log MAR measured for
      the most blurred E was elevated by a relatively small amount for all PDR subjects
      and was not correlated significantly with log sigma(int) (r = 0.40, p = 0.25).
      MAR0, sigma(int), and eta differed significantly between the PDR subjects and the
      controls (all p < 0.05) but sigma(opt) did not (p = 0.50). CONCLUSIONS: Subjects
      with PDR and VA loss had higher than normal equivalent intrinsic blur that
      resulted primarily from neural blur elevations, suggesting that neural blur is an
      important factor that limits VA in these patients.

PMID- 24317137
TI  - When legislators prescribe: policy and practice implications.

PMID- 24317138
TI  - Should children who experience traumatic amputations be offered temporary ectopic
      implantation instead of a prosthesis?

PMID- 24317140
TI  - Home environment, brain injury, & school performance in LBW survivors.
AB  - BACKGROUND: There has been substantial research on low birthweight (LBW) as a
      predictor of adverse educational and cognitive outcomes. LBW infants perform
      worse on cognitive battery tests compared to children born at normal birthweight;
      however, children exposed to similar risks do not all share the same experiences.
      The complex, interrelated factors responsible for poor cognitive and achievement
      performance vary for different populations, but researchers hypothesize that the
      home environment may influence the infants' long-term health outcomes. PURPOSE:
      Examine the home environment as a moderator in the causal pathway from neonatal
      brain injury to school performance in a secondary analysis of a prospectively
      studied, geographically defined cohort from the Neonatal Brain Hemorrhage Study.
      METHOD: The secondary analysis sample included 543 infants with birthweights of
      501 to 2,000 g who were born consecutively in three community hospitals in New
      Jersey between 1984 and 1986. School performance at age 9 was measured by the
      Woodcock-Johnson Tests of Achievement. The home environment variables were tested
      and analyzed using multistep hierarchical regression modeling. RESULTS: A
      moderating effect between the variable neighborhood observations and brain injury
      was demonstrated for the outcome math score. The moderating relationship was
      found in the category of children without brain injury (beta = 1.76, p = .005).
      CONCLUSION: There were statistically significant and potentially clinical
      meaningful models when looking at the home environmental variables as they relate
      to reading and math scores. The findings suggest that at least one variable
      within a LBW child's socio-environmental milieu can moderate the effects of
      perinatal brain injury on school performance outcomes.

PMID- 24317142
TI  - Efficacy of achieving pregnancy with fertility-focused intercourse.
AB  - PURPOSE: To compare pregnancy rates when women have intercourse on self-estimated
      high and peak fertile days and when they only have intercourse on low fertile
      days during the fertile window (FW). STUDY DESIGN AND METHODS: We used a
      prospective observational cohort study design. Our convenience sample included
      124 women who utilized our online charting Web sites to achieve pregnancy from
      January 2010 to November 2012. Participants used an electronic hormonal fertility
      monitor (EHFM) or self-observed cervical mucus or both to determine fertility
      during the estimated FW. Pregnancy rates were determined with Kaplan-Meier
      survival analysis. Chi square analysis was used to evaluate the efficacy of
      achieving pregnancy between two different intercourse patterns. RESULTS: The
      pregnancy rate was 87 per 100 women at 12 months when intercourse happened on
      high or peak days and 5 per 100 when intercourse occurred only on low days of the
      FW. Chi square analysis showed a greater proportion of pregnancies with
      intercourse on high and peak fertile days of the menstrual cycle (x2 = 40.2, p <
      .001, df = 1). NURSING IMPLICATIONS: Focusing intercourse on high or peak fertile
      days during the estimated FW enhances the probability of achieving a desired
      pregnancy. Fertility awareness-based online charting system is effective in
      helping women to determine their FW and target intercourse accordingly to achieve
      pregnancy.

PMID- 24317144
TI  - Still nursing at 6 months: a survey of breastfeeding mothers.
AB  - PURPOSE: To learn about the duration of breastfeeding and to describe the
      variables influencing breastfeeding practices of mothers who gave birth at a
      suburban community hospital. STUDY AND DESIGN: An Institutional Review Board
      approved this descriptive anonymous survey with 20 questions concerning patients'
      characteristics and experiences with breastfeeding, which was developed based on
      current literature. The survey was distributed to mothers through Survey Monkey
      via email 6 months after birth. RESULTS: The survey link was sent to 806 mothers,
      with a response rate of 50%. Over 59% were still breastfeeding at 6 months.
      Mothers who initiated skin-to-skin contact in the first hour had a higher rate of
      breastfeeding during this time frame compared to mothers who did not perform skin
      to-skin contact. Women who had cesarean births and women who were primiparas
      reported a higher use of formula while in the hospital, and breastfed for a
      shorter duration. The primary reasons for stopping breastfeeding were low milk
      supply, returned to work, and baby did not latch and nurse well. CLINICAL
      IMPLICATIONS: This study adds to the knowledge base of what practices influence
      rates and duration of breastfeeding in the first 6 months of a baby's life. The
      information could enhance the care provided to mothers and babies through
      improving lactation programs and thereby increasing breastfeeding success rates.

PMID- 24317145
TI  - Barriers to skin-to-skin care during the postpartum stay.
AB  - PURPOSE: To determine both mothers' and nurses' understanding of barriers to skin
      to-skin care (SSC) during the postpartum hospital stay. STUDY DESIGN: Mixed
      method study including surveys and focus groups with both nurses working in a
      postpartum unit, and mothers who had recently given birth. METHODS: Fourteen
      nurses and 15 mothers completed surveys. Survey questions related to beliefs
      about SSC as well as perceived barriers and were drawn from the literature.
      Additionally, several focus groups with nurses and one focus group with new
      mothers explored attitudes, beliefs, and practices related to SSC, barriers, and
      potential interventions. RESULTS: All nurses indicated that SSC was important for
      both mothers and infants, and identified perceived barriers to the practice. By a
      large margin, visitors in the patient room and others wanting to hold the baby
      were the most frequently cited barriers to SSC. Most nurses believed that mothers
      were unaware of the benefits of SSC and did not spend enough time SSC, yet most
      mothers said that they were aware of the importance of SSC and that they had
      spent enough time SSC. Barriers most often identified by mothers were visitors in
      the room, other people wanting to hold the baby, and safety concerns related to
      feeling groggy. CLINICAL IMPLICATIONS: Identifying barriers to SSC and
      intervening to reduce them may have implications for both maternal role
      development and breastfeeding success, thus positively impacting long-term health
      of mother and child. Studies such as this should be conducted with other
      populations in other centers.

PMID- 24317146
TI  - Supplements: who and why?

PMID- 24317147
TI  - Computerized provider order entry (CPOE): evidence on implementation challenges.

PMID- 24317148
TI  - Throwing starfish: making a difference for this one.

PMID- 24317150
TI  - Burned out? Make a change.

PMID- 24317151
TI  - An MnO2 nanosheet as a label-free nanoplatform for homogeneous biosensing.
AB  - An ultrathin MnO2 nanosheet is established as a label-free two-dimensional
      nanoplatform for homogeneous biosensing. Two biosensors based on an MnO2
      nanosheet with favourable performances are constructed for OTA and Cat D using
      different probes and following different sensing principles. 

PMID- 24317152
TI  - Bullying in children and adolescents: a modifiable risk factor for mental
      illness.

PMID- 24317153
TI  - Is bullying in children and adolescents a modifiable risk factor for mental
      illness?

PMID- 24317154
TI  - Stability and change in the mental health of New Zealand secondary school
      students 2007-2012: results from the national adolescent health surveys.
AB  - OBJECTIVE: To describe the self-reported mental health of New Zealand secondary
      school students in 2012 and to investigate changes between 2007 and 2012.
      METHODS: Nationally representative health and wellbeing surveys of students were
      completed in 2007 (n=9107) and 2012 (n=8500). Logistic regressions were used to
      examine the associations between mental health and changes over time. Prevalence
      data and adjusted odds ratios are presented. RESULTS: In 2012, approximately
      three-quarters (76.2%, 95% CI 74.8-77.5) of students reported good overall
      wellbeing. By contrast (also in 2012), some students reported self-harming
      (24.0%, 95% CI 22.7-25.4), depressive symptoms (12.8%, 95% CI 11.6-13.9), 2 weeks
      of low mood (31%, 95% CI 29.7-32.5), suicidal ideation (15.7%, 95% 14.5-17.0),
      and suicide attempts (4.5%, 95% CI 3.8-5.2). Between 2007 and 2012, there
      appeared to be slight increases in the proportions of students reporting an
      episode of low mood (OR 1.14, 95% CI 1.06-1.23, p=0.0009), depressive symptoms
      (OR 1.16, 95% CI 1.03-1.30, p=0.011), and using the Strengths and Difficulties
      Questionnaire - emotional symptoms (OR 1.38, 95% CI 1.23-1.54, p<0.0001),
      hyperactivity (OR 1.16, 95% CI 1.05-1.29, p=0.0051), and peer problems (OR 1.27,
      95% CI 1.09-1.49, p=0.0022). The proportion of students aged 16 years or older
      reporting self-harm increased slightly between surveys, but there was little
      change for students aged 15 years or less (OR 1.29, 95% CI 1.15-1.44 and OR 1.10,
      95% 0.98-1.23, respectively, p=0.0078). There were no changes in reported
      suicidal ideation and suicide attempts between 2007 and 2012. However, there has
      been an improvement in self-reported conduct problems since 2007 (OR 0.78, 95% CI
      0.70-0.87, p<0.0001). CONCLUSIONS: The findings suggest a slight decline in
      aspects of self-reported mental health amongst New Zealand secondary school
      students between 2007 and 2012. There is a need for ongoing monitoring and for
      evidence-based, accessible interventions that prevent mental ill health and
      promote psychological wellbeing.

PMID- 24317155
TI  - Development of chitosan and polylactic acid based methotrexate intravitreal micro
      implants to treat primary intraocular lymphoma: an in vitro study.
AB  - Primary intraocular lymphoma (PIOL) is an uncommon but clinically and
      pathologically distinct form of non-Hodgkin's lymphoma. It provides a therapeutic
      challenge because of its diverse clinical presentations and variable clinical
      course. Currently available treatments for PIOL include intravenous multiple drug
      chemotherapy, external beam radiation therapy, and intravitreal methotrexate
      (MTX) injection. Each intravitreal injection of MTX is associated with
      potentially toxic peaks and subtherapeutic troughs of intraocular MTX
      concentration. Repetitive injections are required to maintain therapeutic levels
      of MTX in the eye. A sustained release drug delivery system is desired for
      optimized therapeutic release (0.2-2.0 MUg/day) of MTX for over a period of 1
      month to achieve effective treatment of PIOL. This study reports development of a
      unique intravitreal micro-implant, which administers therapeutic release of MTX
      over a period of 1 month. Chitosan (CS) and polylactic acid (PLA) based micro
      implants are fabricated for different MTX loadings (10%, 25%, and 40% w/w).
      First, CS and MTX mixtures are prepared for different drug loadings, and
      lyophilized in Tygon(r) tubing to obtain CS-MTX fibers. The fibers are then cut
      into desired micro-implant lengths and dip coated in PLA for a hydrophobic
      surface coating. The micro-implant is characterized using optical microscopy,
      scanning electron microscopy (SEM), time of flight-secondary ion mass
      spectroscopy (ToF-SIMS), and differential scanning calorimetry (DSC) techniques.
      The release rate studies are carried out using a UV-visible spectrophotometer.
      The total release durations for 10%, 25%, and 40% w/w uncoated CS-MTX micro
      implants are only 19, 29, and 32 h, respectively. However, the therapeutic
      release durations for 10%, 25%, and 40% w/w PLA coated CS-MTX micro-implants
      significantly improved to 58, 74, and 66 days, respectively. Thus, the PLA coated
      CS-MTX micro-implants are able to administer therapeutic release of MTX for more
      than 50 days. The release kinetics of MTX from the coated micro-implants is
      explained by (a) the Korsmeyer-Peppas and zero order model fit (R2 ~ 0.9) of the
      first 60% of the drug release, which indicates the swelling of polymer and
      initial burst release of the drug; and (b) the first order and Higuchi model fit
      (R2 ~ 0.9) from the tenth day to the end of drug release, implying MTX release in
      the therapeutic window depends on its concentration and follows diffusion
      kinetics. The PLA coated CS-MTX micro-implants are able to administer therapeutic
      release of MTX for a period of more than 1 month. The proposed methodology could
      be used for improved treatment of PIOL. 

PMID- 24317156
TI  - A network-based, integrative approach to identify genes with aberrant co
      methylation in colorectal cancer.
AB  - Epigenetic changes, including aberrations in DNA methylation, are a common
      hallmark of many cancers. The identification and interpretation of epigenetic
      changes associated with cancers may benefit from integration with protein
      interactomes. Based on the assumption that genes implicated in a specific tumor
      phenotype will show high aberrant co-methylation patterns with their interacting
      partners, we propose an integrated approach to uncover cancer-associated genes by
      integrating a DNA methylome with an interactome. Aberrant co-methylated
      interactions were first identified in the specific cancer, and genes were then
      prioritized based on their enrichment in aberrant co-methylation. By applying
      this to a large-scale colorectal cancer (CRC) dataset, the proposed method
      increases the power to capture known genes. More importantly, genes possessing
      high aberrant co-methylation patterns, located at the topological center of the
      original protein-protein interaction network (PPIN), affect several cancer
      associated pathways and form hotspots that are frequently hijacked in cancer.
      Additionally, the top-ranked candidate genes may also be useful as an indicator
      of CRC diagnosis and prognosis. Five fold cross-validation of the top-ranked
      genes in diagnosis reveals that it can achieve an area under the receiver
      operating characteristic (ROC) curve ranging from 82.2% to 98.4% in three
      independent datasets. Five of these genes form a core repressive module. CCNA1
      and ESR1 in particular are evidently silenced by promoter hypermethylation in CRC
      cell lines and tissues, whose re-expression markedly suppresses tumor cell
      survival and clonogenicity. These results show that the network-centric method
      could identify novel disease biomarkers and model how oncogenic lesions mediate
      epigenetic changes, providing important insights into tumorigenesis. 

PMID- 24317157
TI  - Effect of pravastatin on echocardiographic circulation parameters in dogs.
AB  - The purpose of this study was to determine the effect of pravastatin (PS) on
      hemodynamic parameters in healthy dogs. Five beagle dogs were repeatedly used in
      each of the 4 groups. One group was not medicated (control). Dogs in other groups
      received 0.5, 1.0 or 2.0 mg/kg PS orally q24hr, for 4 weeks. Physical
      examination, blood biochemical tests, blood pressure measurements and Doppler
      echocardiography were performed before and 1, 2 and 4 weeks after PS
      administration in all dogs. PS significantly reduced the left atrial-to-aortic
      diameter ratio (LA/Ao), early diastolic transmitral flow (E) wave, E/early
      diastolic mitral annulus motion velocity (Em) ratio, left ventricular (LV)
      fractional shortening, LV ejection fraction, mid systolic myocardial velocity
      gradient, stroke volume (SV), cardiac output (CO), right and left ventricular Tei
      indices and elevated Em and early diastolic myocardial velocity gradient. Heart
      rate was not significantly altered during PS administration, but mean blood
      pressure decreased slightly. The hematological and blood biochemical values were
      within normal limits during PS administration. These results revealed that PS
      administration increases LV expansion capacity and decreases LV constriction and
      left atrial pressure. It has been suggested that PS may be effective in improving
      heart failures with LV diastolic dysfunction or elevated left atrial pressure in
      dogs. 

PMID- 24317158
TI  - Dynamics of communities of bacteria and ammonia-oxidizing microorganisms in
      response to simazine attenuation in agricultural soil.
AB  - Autochthonous microbiota plays a crucial role in natural attenuation of s
      triazine herbicides in agricultural soil. Soil microcosm study was carried out to
      investigate the shift in the structures of soil autochthonous microbial
      communities and the potential degraders associated with natural simazine
      attenuation. The relative abundance of soil autochthonous degraders and the
      structures of microbial communities were assessed using quantitative PCR (q-PCR)
      and terminal restriction fragment length polymorphism (TRFLP), respectively.
      Phylogenetic composition of bacterial community was also characterized using
      clone library analysis. Soil autochthonous microbiota could almost completely
      clean up simazine (100 mg kg(-1)) in 10 days after herbicide application,
      indicating a strong self-remediation potential of agricultural soil. A
      significant increase in the proportion of s-triazine-degrading atzC gene was
      found in 6 days after simazine amendment. Simazine application could alter the
      community structures of total bacteria and ammonia-oxidizing archaea (AOA) and
      bacteria (AOB). AOA were more responsive to simazine application compared to AOB
      and bacteria. Actinobacteria, Alphaproteobacteria and Gammaproteobacteria were
      the dominant bacterial groups either at the initial stage after simazine
      amendment or at the end stage of herbicide biodegradation, but Actinobacteria
      predominated at the middle stage of biodegradation. Microorganisms from several
      bacterial genera might be involved in simazine biodegradation. This work could
      add some new insights on the bioremediation of herbicides contaminated
      agricultural soils.

PMID- 24317159
TI  - Pesticide potential dermal exposure during the manipulation of concentrated
      mixtures at small horticultural and floricultural production units in Argentina:
      the formulation effect.
AB  - Potential dermal exposure measurements of horticultural and floricultural field
      operators that handled concentrated pesticides showed a correlation with the
      types of formulations used (liquid or solid) during the mix and load stage. For
      liquid formulations, hand exposure was 22-62 times greater than that for solid
      ones. The dermal exposure mechanism was studied for this formulation under
      laboratory conditions, finding that the rupture of the aluminum seal of the
      pesticide container and the color of the liquid formulation are important
      factors. Additionally, significant external surface contamination of pesticide
      containers collected at horticultural farms was found. This could partially
      account for the differences between the exposure levels of field and laboratory
      experiments for liquid formulations. 

PMID- 24317160
TI  - Arsenic and lead distribution and mobility in lake sediments in the south-central
      Puget Sound watershed: the long-term impact of a metal smelter in Ruston,
      Washington, USA.
AB  - The American Smelting and Refining Company (ASARCO) smelter in Ruston,
      Washington, contaminated the south-central Puget Sound region with heavy metals,
      including arsenic and lead. Arsenic and lead distribution in surface sediments of
      26 lakes is significantly correlated with atmospheric model predictions of
      contaminant deposition spatially, with concentrations reaching 208 mg/kg As and
      1,375 mg/kg Pb. The temporal distribution of these metals in sediment cores is
      consistent with the years of operation of the ASARCO smelter. In several lakes
      arsenic and lead levels are highest at the surface, suggesting ongoing inputs or
      redistribution of contaminants. Moreover, this study finds that arsenic is highly
      mobile in these urban lakes, with maximum dissolved arsenic concentrations
      proportional to surface sediment levels and reaching almost 90 MUg/L As. With 83%
      of the lakes in the deposition zone having surface sediments exceeding published
      "probable effects concentrations" for arsenic and lead, this study provides
      evidence for possible ongoing environmental health concerns.

PMID- 24317161
TI  - Characterization of phosphorus in the sedimentary environments of inundated
      agricultural soils around the Huainan Coal Mines, Anhui, China.
AB  - Extensive coal mining in the Huainan Coal Mines, Anhui China, in light of the
      local hydrology and geology, has resulted in extensive land subsidence and
      submergence around the mines. This has led to the formation of large (>100 km(2))
      lakes. Three representative lakes were selected to study the mechanisms of
      phosphorus (P) unavailability for primary production from the perspective of
      sedimentary environments, which in turn owe their formation to permanently
      inundated agricultural soils. Two important issues were considered: (1) potential
      of P transport from the cultivated soil column toward surface sediments and (2)
      characterization of P behavior in view of regional ecological rehabilitation and
      conservation. Accordingly, we conducted field sediment analyses, combined with
      simulation experiments of soil column inundation/submergence lasting for four
      months. Enrichment of Fe-(hydr)oxides in surface sediments was verified to be the
      main reason for limitations in regional P availability in water bodies. Iron
      (Fe), but not its bound P, moved upward from the submerged soil column to the
      surface. However, an increasing upward gradient in the contents of organic matter
      (OM), total nitrogen (N), total phosphorus (TP), and different P fractions was
      caused by spatial heterogeneity in soil properties. Phosphorus was unable to
      migrate upward toward the surface sediments as envisioned, because of complex
      secondary reactions within soil minerals. Phosphorus bound to Fe and/or Al
      comprised over 50% of TP, which has important implications for local ecological
      rehabilitation and water conservation.

PMID- 24317162
TI  - Sewage epidemiology and illicit drug research: the development of ethical
      research guidelines.
AB  - AIMS: To discuss the need to develop ethical guidelines for researchers using
      sewage epidemiology to monitor drug use in the general population and specific
      precincts, including prisons, schools and workplaces. METHOD: Describe current
      applications of sewage epidemiology, identify potential ethical risks associated
      with this science, and identify key means by which these risks may be mitigated
      through proportionate ethical guidance that allows this science to be fully
      developed. RESULTS: A rapidly advancing field of research is sewage epidemiology
      (SE) - the analysis of wastewater samples to monitor illicit drug use and other
      substances. Typically this research involves low ethical risks because individual
      participants cannot be identified and, consequently, review has been waived by
      human research ethics committees. In the absence of such oversight, ethical
      research guidelines are recommended for SE teams, peer reviewers and journal
      editors; guidelines will assist them to mitigate any risks in general population
      studies and studies of prisons, schools and workplaces. Potential harms include
      the stigmatisation of participants and, in the prison setting, austere policy
      responses to SE data that impact negatively upon inmate-participants. The risk of
      harm can be managed through research planning, awareness of the socio-political
      context in which results will be interpreted (or, in the case of media,
      sensationalised) and careful relations with industry partners. Ethical guidelines
      should be developed in consultation with SE scholars and be periodically amended.
      They should include publication processes that safeguard scientific rigour and be
      promulgated through existing research governance structures. CONCLUSIONS:
      Guidelines will assist to promote an ethical research culture among SE teams and
      scholars involved in the publication process and this will work to protect the
      reputation of the field.

PMID- 24317163
TI  - Spatial characteristics of cadmium in topsoils in a typical e-waste recycling
      area in southeast China and its potential threat to shallow groundwater.
AB  - Informal electrical and electronic waste (e-waste) recycling often creates
      secondary sources of cadmium (Cd) pollution. To characterize the total Cd
      concentration (Cdtotal) in topsoil and evaluate the threat of Cd in topsoils to
      shallow groundwater, 187 topsoil samples and 12 shallow groundwater samples were
      collected in a typical e-waste recycling area in southeast China. Soil organic
      matter content, soil pH and Cdtotal in topsoil, pH and dissolved Cd concentration
      in shallow groundwater were measured. Cdtotal in the topsoils showed an inverse
      distribution trend with soil pH in that high Cd concentrations (and low pH
      values) were found in the surrounding area of the metal recycling industrial park
      where there were many family-operated e-waste recycling facilities before the
      industrial park was established and with low concentrations (and high pH values)
      in other areas, and they had similar spatial correlation structures. Cd
      accumulation and acidification were synchronous in topsoils, and soil pH was
      significantly correlated with Cdtotal in topsoils with low to moderate negative
      correlation coefficient (r=-0.24), indicating that both of them maybe correlated
      with informal recycling. The shallow groundwater in the surrounding area of the
      metal recycling industrial park was seriously contaminated by Cd, and topsoil Cd
      accumulation and acidification in the surrounding area of e-waste recycling sites
      significantly increase the risk of shallow groundwater contaminated by Cd. Action
      is urgently required to control Cd accumulation and acidification by improving
      the recycling operations of e-wastes in order to reduce the risk of Cd leaching
      from topsoils and shallow groundwater contamination.

PMID- 24317164
TI  - Dioxin-like, non-dioxin like PCB and PCDD/F contamination in European eel
      (Anguilla anguilla) from the Loire estuarine continuum: spatial and biological
      variabilities.
AB  - To characterize the eel contamination by dioxin-like (dl) and non dioxin-like
      (ndl) polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and
      furans (PCDD/Fs), sixty-two eels from the Loire estuary (France) were analyzed.
      PCB contamination significantly increased from glass eel stage (3.71 +/- 1.85 and
      15.2 +/- 4.2 ng g(-1) dw) to other life stages (for yellow eels: 62.8 +/- 34.4
      and 382 +/- 182 ng g(-1) dw; for silver eels: 93.7 +/- 56.3 and 463 +/- 245 ng g(
      1) dw respectively for dl and ndl-PCBs). An inter-site variability based on PCB
      levels and profiles was observed among the three studied sites. For glass eels,
      the profile was mainly characterized by less chlorinated PCBs contrary to the
      other eels, displaying a different bioaccumulation pathway. Overall, the
      contamination level in the eels from this estuary was shown to be low for PCDD/Fs
      and intermediate for dl and ndl-PCBs, compared to other international/national
      areas. However, more than 60% of the studied silver eels displayed higher values
      for PCDD/F and dl-PCB WHO2005 TEQ than the EU permissible level of 10 pg g(-1)
      ww. This statement suggests a potential exposure to PCBs through eel consumption,
      especially with silver eels, and also points out apparent contamination that
      could eventually affect the reproductive success of the species.

PMID- 24317165
TI  - Oxidative potential of particulate matter collected at sites with different
      source characteristics.
AB  - BACKGROUND: The oxidative potential (OP) of particulate matter (PM) has been
      proposed as a more health relevant metric than PM mass. Different assays exist
      for measuring OP and little is known about how the different assays compare. AIM:
      To assess the OP of PM collected at different site types and to evaluate
      differences between locations, size fractions and correlation with PM mass and PM
      composition for different measurement methods for OP. METHODS: PM2.5 and PM10 was
      sampled at 5 sites: an underground station, a farm, 2 traffic sites and an urban
      background site. Three a-cellular assays; dithiothreitol (OP(DTT)), electron spin
      resonance (OP(ESR)) and ascorbate depletion (OP(AA)) were used to characterize
      the OP of PM. RESULTS: The highest OP was observed at the underground, where OP
      of PM10 was 30 (OP(DTT)) to >600 (OP(ESR)) times higher compared to the urban
      background when expressed as OP/m(3) and 2-40 times when expressed as OP/MUg. For
      the outdoor sites, samples from the farm showed significantly lower OP(ESR) and
      OP(AA), whereas samples from the continuous traffic site showed the highest OP
      for all assays. Contrasts in OP between sites were generally larger than for PM
      mass and were lower for OP(DTT) compared to OP(ESR) and OP(AA). Furthermore,
      OP(DTT)/MUg was significantly higher in PM2.5 compared to PM10, whereas the
      reverse was the case for OP(ESR). OP(ESR) and OP(AA) were highly correlated with
      traffic-related PM components (i.e. EC, Fe, Cu, PAHs), whereas OP(DTT) showed the
      highest correlation with PM mass and OC. CONCLUSIONS: Contrasts in OP between
      sites, differences in size fractions and correlation with PM composition depended
      on the specific OP assay used, with OP(ESR) and OP(AA) showing the most similar
      results. This suggests that either OP(ESR) or OP(AA) and OP(DTT) can complement
      each other in providing information regarding the oxidative properties of PM,
      which can subsequently be used to study its health effects.

PMID- 24317166
TI  - Studies on the anoxic dissipation and metabolism of pyribambenz propyl (ZJ0273)
      in soils using position-specific radiolabeling.
AB  - Pyribambenz propyl (ZJ0273) is a polycyclic herbicide with increasing use,
      although studies show that it tends to be persistent in soil and pose
      phytotoxicity to rotational crops. This study employed an improved ring-specific
      (14)C labeling method to characterize its anoxic metabolism, with (14)C
      positioned on the benzoate, pyrimidyl or benzyl rings. Separation and
      identification of the metabolites were achieved by liquid chromatography (LC),
      ultralow-level liquid scintillation spectrometry, and LC-mass spectrometry (MS).
      Results show that the anoxic degradation follows first-order kinetics and the
      half-lives are approximately 38.7, 50.2 and 70.7d for loamy, saline and clayey
      soils, respectively. A total of five radioactive intermediates (M1-M5) were
      detected, and due to the loss of radiolabels, different radiochromatograms were
      obtained from different labels, i.e., radioactive M5 was only detected for
      pyrimidinyl-(14)C; M3 and M4 were only detected for pyrimidinyl-(14)C and benzyl
      (14)C, while M1 and M2 were detected for all labels. Based on their appearance
      pattern and fragmentations from LC-MS, the structures of M1-M5 were identified,
      and they were proposed to form by reactions such as de-estering, hydrolysis,
      acylation, CN cleavage, and demethylation. All metabolites have been previously
      detected in aerobic soils except M4, which is a demethylation product from M3,
      and identified as 2-(4-hydroxy-6-methoxypyrimidin-2-yloxy)benzoic acid. The
      results show that ZJ0273 is more persistent in anoxic soils, and its degradation
      pathways and intermediates are different from aerobic metabolism and differ with
      the soil types, suggesting that soil-specific and farming practices may be
      important considerations in the use of this herbicide. The ring-specific labeling
      provides full molecular information about the referred compound and guarantees
      the reliability of the results, and can be used as an effective tool for
      metabolite profiling of polycyclic compounds. 

PMID- 24317167
TI  - The future of Yellowcake: a global assessment of uranium resources and mining.
AB  - Uranium (U) mining remains controversial in many parts of the world, especially
      in a post-Fukushima context, and often in areas with significant U resources.
      Although nuclear proponents point to the relatively low carbon intensity of
      nuclear power compared to fossil fuels, opponents argue that this will be eroded
      in the future as ore grades decline and energy and greenhouse gas emissions
      (GGEs) intensity increases as a result. Invariably both sides fail to make use of
      the increasingly available data reported by some U mines through sustainability
      reporting - allowing a comprehensive assessment of recent trends in the energy
      and GGE intensity of U production, as well as combining this with reported
      mineral resources to allow more comprehensive modelling of future energy and GGEs
      intensity. In this study, detailed data sets are compiled on reported U resources
      by deposit type, as well as mine production, energy and GGE intensity. Some
      important aspects included are the relationship between ore grade, deposit type
      and recovery, which are crucial in future projections of U mining. Overall, the
      paper demonstrates that there are extensive U resources known to meet potential
      short to medium term demand, although the future of U mining remains uncertain
      due to the doubt about the future of nuclear power as well as a range of complex
      social, environmental, economic and some site-specific technical issues. 

PMID- 24317168
TI  - Emergy evaluation using the calculation software SCALE: case study, added value
      and potential improvements.
AB  - This paper reports the emergy-based evaluation (EME) of the ecological
      performance of four water treatment plants (WTPs) using three different
      approaches. The results obtained using the emergy calculation software SCALE
      (EMESCALE) are compared with those achieved through a conventional emergy
      evaluation procedure (EMECONV), as well as through the application of the Solar
      Energy Demand (SED) method. SCALE's results are based on a detailed
      representation of the chain of technological processes provided by the lifecycle
      inventory database ecoinvent(r). They benefit from a higher level of details in
      the description of the technological network as compared to the ones calculated
      with a conventional EME and, unlike the SED results, are computed according to
      the emergy algebra rules. The analysis delves into the quantitative comparison of
      unit emergy values (UEVs) for individual technospheric inputs provided by each
      method, demonstrating the added value of SCALE to enhance reproducibility,
      accurateness and completeness of an EME. However, SCALE cannot presently include
      non-technospheric inputs in emergy accounting, like e.g. human labor and
      ecosystem services. Moreover, SCALE is limited by the approach used to build the
      dataset of UEVs for natural resources. Recommendations on the scope and accuracy
      of SCALE-based emergy accounting are suggested for further steps in software
      development, as well as preliminary quantitative methods to account for ecosystem
      services and human labor. 

PMID- 24317169
TI  - In vitro assessment of thyroidal and estrogenic activities in poultry and broiler
      manure.
AB  - Among the many chemicals found in avian manure, endocrine disruptors (EDs), of
      natural or anthropogenic origin, are of special environmental concern. Nowadays,
      an increasing amount of estrogens is being released into the environment via the
      use of manure to fertilize agricultural land. While most research in this field
      has focused on estrogenic phenomena, little is known about alterations related to
      other endocrine systems, such as the thyroidal one. Here we simultaneously
      assessed the potential estrogenic and thyroidal activity of poultry and broiler
      litter manure using in vitro approaches based on estrogen receptor (Er) and
      thyroid receptor (Tr) transactivation assays. In addition, leaching experiments
      were performed to assess whether the EDs present in the manure pass through a
      soil column and potentially reach the groundwater. Manure from four broiler and
      four poultry farms was collected in two sampling campaigns carried out in two
      seasons (fall and spring). Extracts from broiler and poultry manure exhibited
      strong thyroidal activity. Only poultry manure showed estrogenic activity, which
      is consistent with the low levels of estrogens expected in hatchlings. Leakage
      experiments were performed in columns with two kinds of arable soils: sandy and
      loamy. No estrogenicity or thyroidal activity was detectable in soils treated
      with the manure or in the corresponding leachates. These results indicate that
      substances with estrogenic or thyroidal activity were degraded in the soil under
      our experimental conditions. However, the long-term effects associated with the
      constant and intensive application of manure to agricultural land in some regions
      require further research. 

PMID- 24317170
TI  - The role of root exuded low molecular weight organic anions in facilitating
      petroleum hydrocarbon degradation: current knowledge and future directions.
AB  - Rhizoremediation is a bioremediation technique whereby enhanced microbial
      degradation of organic contaminants occurs within the plant root zone
      (rhizosphere). It is considered an effective and affordable 'green technology'
      for remediating soils contaminated with petroleum hydrocarbons (PHCs). This paper
      critically reviews the potential role of root exuded compounds in
      rhizoremediation, with emphasis on commonly exuded low molecular weight aliphatic
      organic acid anions (carboxylates). The extent to which remediation is achieved
      shows wide disparity among plant species. Therefore, plant selection is crucial
      for the advancement and widespread adoption of this technology. Root exudation is
      speculated to be one of the predominant factors leading to microbial changes in
      the rhizosphere and thus the potential driver behind enhanced petroleum
      biodegradation. Carboxylates can form a significant component of the root exudate
      mixture and are hypothesised to enhance petroleum biodegradation by: i) providing
      an easily degradable energy source; ii) increasing phosphorus supply; and/or iii)
      enhancing the contaminant bioavailability. These differing hypotheses, which are
      not mutually exclusive, require further investigation to progress our
      understanding of plant-microbe interactions with the aim to improve plant species
      selection and the efficacy of rhizoremediation. 

PMID- 24317171
TI  - Salmonella and antimicrobial resistance in an animal-based agriculture river
      system.
AB  - The aim of this study was to examine the Salmonella serovars and antimicrobial
      resistance within an animal-based agriculture river system. The study area
      consisted of a 1,345 ha upper part of Pinhal catchment. A total of 384 samples
      were collected in four years of monitoring. Salmonella was isolated from 241
      samples (62.7%), resulting in 324 isolates. The highest number of Salmonella sp.
      occurred in samples associated with sites with high stoking density animal unit
      per hectare. It was possible to demonstrate the variability of serovars in the
      study area: 30 different serovars were found and at least 11 per monitoring site.
      Thirty-three potentially related isolates were genotyped by PFGE, one major clone
      was observed in serovar Typhimurium, which occurred in animal feces (swine and
      bovine), and different sites and samplings proving the cross-contamination and
      persistence of this specific clone. Among 180 isolates submitted to an
      antimicrobial susceptibility test, 50.5% were susceptible to all 21
      antimicrobials tested and 54 different profiles were found. In the current study,
      49.5% of the tested isolates were resistant to at least one antimicrobial, and
      multi-resistance occurred in 18% of isolates. Results indicate a close
      interaction between animal-based agriculture, Salmonella, and antimicrobial
      resistance.

PMID- 24317172
TI  - Small-scale microcosms to detect chemical induced changes in soil nematode
      communities--effects of crystal proteins and Bt-maize plant material.
AB  - Small-scale laboratory microcosms (30 g soil in 50 ml tubes) were evaluated for
      their suitability to assess the impact of chemicals on in situ soil nematode
      communities. For this purpose, appropriate conditions in the microcosms were
      explored to ensure stable conditions and a homogenous distribution of the
      nematodes. Then, the microcosms were used to assess the toxicity of insecticidal
      crystal proteins (Cry1A.105, Cry2Ab2, Cry3Bb1) present in genetically modified
      maize (MON89034*MON88017) on in situ nematode communities. Highly abundant and
      genus rich nematode communities could be maintained over a period of 12 weeks.
      Due to a low variance between the replicates of the treatments, low detection
      limits could be achieved. Using meaningful stress indices, such as the maturity
      indices, the microcosm study revealed dose-dependent effects of the insecticidal
      Cry proteins that could be verified as toxic effects by comparing with effects of
      two positive controls (Cu, nematicidal Cry5B). Moreover, toxic effects could be
      differentiated from organic enrichment effects that were induced by the addition
      of plant material. With a NOECCommunity of 0.1 mg kg(-1) dry wt, the nematode
      communities reacted considerably more sensitive to the Cry proteins than a single
      species nematode toxicity test (NOEC: 29 mg l(-1)). The small-scale microcosm set
      up turned out to be a suitable, low-budget tool for assessing the toxicity of
      chemicals on soil nematodes on community level, representing a link between
      single-species toxicity tests and large scale outdoor mesocosms.

PMID- 24317173
TI  - Arsenic exposure triggers a shift in microRNA expression.
AB  - Exposure to inorganic Arsenic (iAs) through drinking water is a major public
      health problem affecting most countries. iAs has been classified by the
      International Agency for Research on Cancer as Group 1: "Carcinogenic to humans".
      Although numerous studies have shown the related adverse effects of iAs,
      sensitive appropriate biomarkers for studies of environmental epidemiology are
      still required. The present work aims at investigate the role of microRNAs
      (miRNAs), powerful negative regulators of gene expression, playing a key role in
      many physiological and pathological cellular processes, in iAs exposure. To this
      end, we analyzed miRNA changes in expression profile triggered by iAs exposure in
      Jurkat cell line. We used microarray technology to profile the expression of
      miRNAs following 2 MUmol/L sodium arsenite treatment at different time points.
      Moreover, we performed phenotypic analysis of iAs treated cells. Real Time
      Polymerase Chain Reaction (RT-PCR) was used to validate miRNA microarray data and
      to assay expression modulation of selected relevant mRNAs. Finally,
      bioinformatics techniques were applied to reconstruct iAs-relevant molecular
      pathways and miRNA regulatory networks from the expression data. We report miRNAs
      modulated after iAs treatment in Jurkat cells. In particular, we highlight 36
      miRNAs exhibiting consistent dysregulation and particularly a panel of 8 miRNAs
      which we also validated by RT-PCR analysis. Computational analysis of lists of
      putative target genes for these 8 miRNAs points to an involvement in arsenic
      response pathways, for a subset of them, that were analyzed by RT-PCR.
      Furthermore, iAs exposure reveals induction of cell cycle progression and the
      failure of apoptosis, supporting the idea of iAs carcinogenic activity. Our study
      provides a list of miRNAs whose expression levels are affected by iAs treatment,
      corroborating the importance of proceeding with the hunt for specific subset of
      miRNAs, which can serve as potential biomarkers of iAs effects with useful
      diagnostic value.

PMID- 24317175
TI  - Genome-wide association studies meet chemoprevention.

PMID- 24317174
TI  - Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer
      according to CTNNB1 alterations.
AB  - BACKGROUND: Regular aspirin use reduces the risk for colorectal cancer (CRC),
      possibly through inhibition of WNT/cadherin-associated protein beta1 (CTNNB1 or
      beta-catenin) signaling. The single nucleotide polymorphism (SNP) rs6983267 on
      chromosome 8q24 is a CRC susceptibility locus that affects binding activity of
      transcription factor 7 like-2 (TCF7L2) to CTNNB1, thereby altering expression of
      target oncogenes, including MYC. METHODS: We evaluated regular aspirin use and
      CRC risk according to genotypes of SNP rs6983267 and CTNNB1 expression status in
      two prospective case-control studies (840 CRC case patients and 1686 age- and
      race-matched control subjects) nested within the Nurses' Health Study and the
      Health Professionals Follow-up Study. We estimated odds ratios (ORs) and 95%
      confidence intervals (CIs) using unconditional logistic regression models. All
      statistical tests were two-sided. RESULTS: A lower risk of CRC was associated
      with regular aspirin use and the T allele of rs6983267. The effect of aspirin was
      confined to individuals with protective T allele of rs6983267 (additive matching
      factors-adjusted OR for T allele = 0.83; 95% CI = 0.74 to 0.94; P trend = .002; P
      interaction = .01). Additionally, the T allele of rs6983267 was associated with a
      reduced expression of MYC oncogene (P trend = .03). Moreover, among individuals
      with protective T allele, the effect of regular aspirin use was limited to those
      with positive nuclear CTNNB1 expression. In a functional analysis, in vitro
      treatment of LS174T cells (a cell line heterozygous for rs6983267) with aspirin
      was statistically significantly associated with higher G/T allelic ratio of
      TCF7L2 immunoprecipitated DNA (P = .03). CONCLUSIONS: Our results support an
      influence of aspirin on WNT/CTNNB1 signaling and suggest that aspirin
      chemoprevention may be tailored according to rs6983267 genotype.

PMID- 24317176
TI  - Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM
      trial.
AB  - BACKGROUND: At the time of the initial analysis of overall survival (OS) for the
      Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM)
      randomized, double-blind, phase III trial, approximately 50% of patients had
      died. A final analysis of OS was subsequently planned for when 75% of patients
      had died. METHODS: Patients were randomly assigned 1:1 to fulvestrant 500 mg
      administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every
      28 (+/-3) days thereafter or fulvestrant 250 mg administered as two 5-mL
      intramuscular injections (one fulvestrant and one placebo [identical in
      appearance to study drug]) on days 0, 14 (two placebo injections only), and 28
      and every 28 (+/-3) days thereafter. OS was analyzed using an unadjusted log-rank
      test. No adjustments were made for multiplicity. Serious adverse events (SAEs)
      and best response to subsequent therapy were also reported. All statistical tests
      were two-sided. RESULTS: In total, 736 women (median age = 61.0 years) were
      randomly assigned to fulvestrant 500 mg (n = 362) or 250 mg (n = 374). At the
      final survival analysis, 554 of 736 (75.3%) patients had died. Median OS was 26.4
      months for fulvestrant 500 mg and 22.3 months for 250 mg (hazard ratio = 0.81;
      95% confidence interval = 0.69-0.96; nominal P = .02). There were no clinically
      important differences in SAE profiles between the treatment groups; no clustering
      of SAEs could be detected in either treatment group. Type of first subsequent
      therapy and objective responses to first subsequent therapy were well balanced
      between the two treatment groups. CONCLUSIONS: In patients with locally advanced
      or metastatic estrogen receptor-positive breast cancer, fulvestrant 500 mg is
      associated with a 19% reduction in risk of death and a 4.1-month difference in
      median OS compared with fulvestrant 250 mg. Fulvestrant 500 mg was well
      tolerated, and no new safety concerns were identified.

PMID- 24317177
TI  - Factors contributing to underuse of radiation among younger women with breast
      cancer.
AB  - BACKGROUND: Evidence-based literature has confirmed the effectiveness of
      radiation therapy (RT) after breast-conserving surgery (BCS), especially for
      young women. However, women with young children may be less likely to be
      compliant. This study explores factors associated with noncompliance of RT among
      insured young patients. METHOD: Using the MarketScan Database, we identified the
      study cohort as women aged 20 to 64 years who had a BCS between January 1, 2004,
      and December 31, 2009, and had continuous enrollment 12 months before and after
      the date of BCS. Patients who had any radiation claims within a year of BCS were
      considered compliant. Adjusted odds of compliance were estimated from logistic
      regressions for the full sample and age-stratified subgroups. Sensitivity
      analyses were performed to evaluate the robustness of study findings. All
      statistical tests were two-sided. RESULTS: Eighteen thousand one hundred twenty
      of 21 008 (86.25%) nonmetastatic BCS patients received RT. Among patients aged 20
      to 64 years, those with children aged 7 to 12 years, those with children aged 13
      to 17 years, and those with no children or children aged 18 years or older were
      more likely to receive RT than patients with at least one child aged less than 7
      years (7-12 years: odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.05 to
      1.66, P = .02; 13-17 years: OR = 1.41, 95% CI = 1.13 to 1.75, P = .002; no
      children or >=18 years: OR = 1.38, 95% CI = 1.13 to 1.68, P = .001). Stratified
      analyses showed that the above association was primarily driven by women in the
      youngest age group (aged 20-50). Other important factors included breast cancer
      quality of care measures, enrollment in health maintenance organizations or
      capitated preferred provider organizations, travelled to a Census division
      outside their residence for BCS, and whether patients were primary holders of the
      insurance policy. CONCLUSIONS: Competing demands from child care can constitute a
      barrier to complete guideline-concordant breast cancer therapy. Younger patients
      may be confronted by unique challenges that warrant more attention in future
      research.

PMID- 24317178
TI  - Germline mutations in driver oncogenes and inherited lung cancer risk independent
      of smoking history.

PMID- 24317179
TI  - Lifetime cigarette smoking and breast cancer prognosis in the After Breast Cancer
      Pooling Project.
AB  - BACKGROUND: There is controversy on whether former smokers have increased risk
      for breast cancer recurrence or all-cause mortality, regardless of how much they
      smoked. METHODS: Data were from three US cohorts in the After Breast Cancer
      Pooling Project, with detailed information on smoking among 9975 breast cancer
      survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed
      entry Cox proportional hazards models were used to examine the relationships of
      smoking status, cigarettes per day, years of smoking, and pack years with breast
      cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast
      cancer mortality (n = 1059), and overall mortality (n = 1803). RESULTS: Compared
      with never smokers, former smokers with less than 20 pack-years of exposure had
      no increased risk of any outcome. However, former smokers with 20 to less than
      34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence
      (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26%
      increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For
      former smokers with 35 or more pack-years of exposure, the probability of
      recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer
      mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause
      mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking
      increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to
      1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to
      2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to
      2.54). CONCLUSIONS: Lifetime cigarette smoking was statistically significantly
      associated with a poor prognosis among women diagnosed with breast cancer, dose
      dependent increased risks of recurrence, and breast cancer and all-cause
      mortality.

PMID- 24317180
TI  - Novel germline mutation in the transmembrane domain of HER2 in familial lung
      adenocarcinomas.
AB  - We encountered a family of Japanese descent in which multiple members developed
      lung cancer. Using whole-exome sequencing, we identified a novel germline
      mutation in the transmembrane domain of the human epidermal growth factor
      receptor 2 (HER2) gene (G660D). A novel somatic mutation (V659E) was also
      detected in the transmembrane domain of HER2 in one of 253 sporadic lung
      adenocarcinomas. Because the transmembrane domain of HER2 is considered to be
      responsible for the dimerization and subsequent activation of the HER family and
      downstream signaling pathways, we performed functional analyses of these HER2
      mutants. Mutant HER2 G660D and V659E proteins were more stable than wild-type
      protein. Both the G660D and V659E mutants activated Akt. In addition, they
      activated p38, which is thought to promote cell proliferation in lung
      adenocarcinoma. Our findings strongly suggest that mutations in the transmembrane
      domain of HER2 may be oncogenic, causing hereditary and sporadic lung
      adenocarcinomas. 

PMID- 24317182
TI  - Plasma alkylresorcinols as a biomarker for whole-grain intake and association
      with colorectal cancer.

PMID- 24317183
TI  - Combined surface plasmon resonance and impedance spectroscopy systems for
      biosensing.
AB  - Combined surface plasmon resonance and electrochemical impedance spectroscopy (SP
      EIS) biosensing systems have been developed. They use a sensor chip consisting of
      micrometer sized interdigitated metal electrodes (IDEs) which effectively act as
      a surface plasmon supporting structure. In addition, the interdigitated
      electrodes exhibit the properties of an optical dispersive grating reflecting
      white light into the diffraction orders. Direct surface plasmon spectral analysis
      is possible by using the first order of diffraction and has been used as a novel
      principle for a simplified optical set-up. SP-EIS is a promising technology for a
      variety of conductometric and SPR mono- and multisensing applications in portable
      or stationary platforms. 

PMID- 24317181
TI  - Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and
      incidence of colorectal cancer.
AB  - BACKGROUND: Few studies have investigated the association between whole-grain
      intake and colorectal cancer. Because whole-grain intake estimation might be
      prone to measurement errors, more objective measures (eg, biomarkers) could
      assist in investigating such associations. METHODS: The association between
      alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal
      cancer incidence were investigated using prediagnostic plasma samples from
      colorectal cancer case patients and matched control subjects nested within the
      European Prospective Investigation into Cancer and Nutrition. We included 1372
      incident colorectal cancer case patients and 1372 individual matched control
      subjects and calculated the incidence rate ratios (IRRs) for overall and
      anatomical subsites of colorectal cancer using conditional logistic regression
      adjusted for potential confounders. Regional differences (Scandinavia, the
      Mediterranean, Central Europe) were also explored. RESULTS: High plasma total
      alkylresorcinol concentration was associated with lower incidence of distal colon
      cancer; the adjusted incidence rate ratio of distal colon cancer for the highest
      vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence
      interval [CI] = 0.28 to 0.83). An inverse association between plasma total
      alkylresorcinol concentrations and colon cancer was found for Scandinavian
      participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma
      total alkylresorcinol concentrations were not associated with overall colorectal
      cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols
      concentrations were associated with colon and distal colon cancer only in Central
      Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher).
      CONCLUSIONS: High concentrations of plasma alkylresorcinols were associated with
      a lower incidence of distal colon cancer but not with overall colorectal cancer,
      proximal colon cancer, and rectal cancer.

PMID- 24317184
TI  - Cytotoxicity study on SH-SY5Y cells cultured at high glucose levels and treated
      with bupivacaine.
AB  - The aim of this study was to investigate susceptibility to the neurotoxicity of
      local anesthetic agents in a model of gestational diabetes mellitus (GDM). SH
      SY5Y cells were cultured at different concentrations of glucose and subsequently
      treated with 1 mmol/l bupivacaine for 6 h. Reactive oxygen species (ROS)
      production and apoptosis were assessed using flow cytometry in each group of
      cells. The MTT method was utilized to detect cell survival, and western blot
      analysis was used to examine changes in 78 kDa glucose-regulated protein (GRP78)
      levels in neuronal cells. In all groups, levels of ROS production, cell survival
      and GRP78 expression were significantly different (P<0.01) following the addition
      of various concentrations of glucose and bupivacaine, as well as for the
      interaction between different concentrations of the anesthetic agents,
      demonstrating a statistically significant difference. In conclusion, the
      susceptibility of SH-SY5Y cells to the neurotoxicity of local anesthetic agents
      was enhanced in a model of GDM.

PMID- 24317185
TI  - Treadmill walking effects on grip strength in young men with Down syndrome.
AB  - This study was aimed at investigating the relation between grip strength and
      anthropometric factors and the impact of an aerobic exercise on grip strength in
      young men with Down syndrome (DS). This study was a pre-post design. Twelve males
      with DS were assigned to an exercise group, who walked using an incremental
      protocol on a treadmill for 20 min at aerobic levels. Eight additional persons
      with DS were assigned to an attentional control group, who watched a video.
      Measure of grip strength was tested pre- and post-interventions. The results
      showed positively significant relationship among grip strength and age (r=.74,
      p<.01), weight (r=.52, p=.02), body mass index (r=.61, p=.01) and waist
      circumference (r=.54, p=.02). In addition, Grip strength was slightly improved
      after exercise (p=.03) but decreased after control condition. The results showed
      that anthropometric factors, such as age, weight, body mass index and waist
      circumference, were positively correlated with grip strength in young men with
      DS. Further, improvement in grip strength can be found even after a single
      exercise session. This finding emphasizes the importance of maintaining an active
      lifestyle in persons with DS for performing activities of daily living.

PMID- 24317186
TI  - Crossover from incoherent to coherent phonon scattering in epitaxial oxide
      superlattices.
AB  - Elementary particles such as electrons or photons are frequent subjects of wave
      nature-driven investigations, unlike collective excitations such as phonons. The
      demonstration of wave-particle crossover, in terms of macroscopic properties, is
      crucial to the understanding and application of the wave behaviour of matter. We
      present an unambiguous demonstration of the theoretically predicted crossover
      from diffuse (particle-like) to specular (wave-like) phonon scattering in
      epitaxial oxide superlattices, manifested by a minimum in lattice thermal
      conductivity as a function of interface density. We do so by synthesizing
      superlattices of electrically insulating perovskite oxides and systematically
      varying the interface density, with unit-cell precision, using two different
      epitaxial-growth techniques. These observations open up opportunities for studies
      on the wave nature of phonons, particularly phonon interference effects, using
      oxide superlattices as model systems, with extensive applications in
      thermoelectrics and thermal management. 

PMID- 24317187
TI  - A nanoparticle-based strategy for the imaging of a broad range of tumours by
      nonlinear amplification of microenvironment signals.
AB  - Stimuli-responsive nanomaterials are increasingly important in a variety of
      applications such as biosensing, molecular imaging, drug delivery and tissue
      engineering. For cancer detection, a paramount challenge still exists in the
      search for methods that can illuminate tumours universally regardless of their
      genotypes and phenotypes. Here we capitalized on the acidic, angiogenic tumour
      microenvironment to achieve the detection of tumour tissues in a wide variety of
      mouse cancer models. This was accomplished using ultra pH-sensitive fluorescent
      nanoprobes that have tunable, exponential fluorescence activation on encountering
      subtle, physiologically relevant pH transitions. These nanoprobes were silent in
      the circulation, and then strongly activated (>300-fold) in response to the
      neovasculature or to the low extracellular pH in tumours. Thus, we have
      established non-toxic, fluorescent nanoreporters that can nonlinearly amplify
      tumour microenvironmental signals, permitting the identification of tumour tissue
      independently of histological type or driver mutation, and detection of acute
      treatment responses much more rapidly than conventional imaging approaches. 

PMID- 24317189
TI  - Room-temperature Bose-Einstein condensation of cavity exciton-polaritons in a
      polymer.
AB  - A Bose-Einstein condensate (BEC) is a state of matter in which extensive
      collective coherence leads to intriguing macroscopic quantum phenomena. In
      crystalline semiconductor microcavities, bosonic quasiparticles, known as exciton
      polaritons, can be created through strong coupling between bound electron-hole
      pairs and the photon field. Recently, a non-equilibrium BEC (ref. ) and
      superfluidity have been demonstrated in such structures. With organic crystals
      grown inside dielectric microcavities, signatures of polariton lasing have been
      observed. However, owing to the deleterious effects of disorder and material
      imperfection on the condensed phase, only crystalline materials of the highest
      quality have been used until now. Here we demonstrate non-equilibrium BEC of
      exciton-polaritons in a polymer-filled microcavity at room temperature. We
      observe thermalization of polaritons and, above a critical excitation density,
      clear evidence of condensation at zero in-plane momentum, namely nonlinear
      behaviour, blueshifted emission and long-range coherence. The key signatures
      distinguishing the behaviour from conventional photon lasing are presented. As no
      crystal growth is involved, our approach radically reduces the complexity of
      experiments to investigate BEC physics and paves the way for a new generation of
      opto-electronic devices, taking advantage of the processability and flexibility
      of polymers. 

PMID- 24317188
TI  - Semi-metallic polymers.
AB  - Polymers are lightweight, flexible, solution-processable materials that are
      promising for low-cost printed electronics as well as for mass-produced and large
      area applications. Previous studies demonstrated that they can possess
      insulating, semiconducting or metallic properties; here we report that polymers
      can also be semi-metallic. Semi-metals, exemplified by bismuth, graphite and
      telluride alloys, have no energy bandgap and a very low density of states at the
      Fermi level. Furthermore, they typically have a higher Seebeck coefficient and
      lower thermal conductivities compared with metals, thus being suitable for
      thermoelectric applications. We measure the thermoelectric properties of various
      poly(3,4-ethylenedioxythiophene) samples, and observe a marked increase in the
      Seebeck coefficient when the electrical conductivity is enhanced through
      molecular organization. This initiates the transition from a Fermi glass to a
      semi-metal. The high Seebeck value, the metallic conductivity at room temperature
      and the absence of unpaired electron spins makes polymer semi-metals attractive
      for thermoelectrics and spintronics. 

PMID- 24317190
TI  - A longitudinal study of knee pain in older men: Concord Health and Ageing in Men
      Project.
AB  - BACKGROUND: chronic knee pain is still considered a fairly benign disease by
      many, an 'unavoidable' consequence of ageing. This passive acceptance may be
      unnecessarily exposing older people to disability and serious co-morbidity. The
      aim of this study was to determine the disease burden associated with chronic
      knee pain and the role of knee extensor strength as a modifiable risk factor.
      METHODS: a longitudinal cohort study with 2-year follow-up conducted among 1,587
      community-dwelling men aged 70 years and over, 637 (40%) reported chronic knee
      pain. Of the 950 (60%) men without knee pain at baseline, 768 (81%) returned for
      the follow-up assessment with 150 (20%) reporting incident chronic knee pain.
      RESULTS: knee pain was significantly associated with marked mobility disability
      [odds ratio (OR) 2.38; 95% confidence interval (CI) 1.74-3.29], falls (OR: 1.31;
      95% CI: 1.01-1.70) and having four or more co-morbidity (OR: 1.63; 95% CI: 1.16
      2.30) as well as reduced knee extensor strength and mass (dual X-ray
      absorptiometry). Men with incident knee pain at the 2-year follow-up assessment
      demonstrated greater increases in these measures of disease burden and greater
      decreases in muscle strength and mass, compared with those without incident
      chronic knee pain. Obesity, high co-morbidity burden, back pain, higher levels of
      physical activity or low knee extensor strength were all significant risk factors
      for incident knee pain. CONCLUSION: prevention of chronic knee pain may reduce a
      considerable burden of mobility disability and increased risk of serious co
      morbidity among older men.

PMID- 24317191
TI  - Anastomotic leak after bowel resection.

PMID- 24317192
TI  - Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for
      local recurrence after radiation therapy failure.
AB  - PURPOSE: The aim of the present retrospective study is to evaluate toxicity and
      early clinical outcomes of interstitial hyperthermia (IHT) combined with high
      dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy
      confirmed local recurrence of prostate cancer after previous external beam
      radiotherapy. PATIENTS AND METHODS: Between September 2008 and March 2013, 25
      patients with local recurrence of previously irradiated prostate cancer were
      treated. The main eligibility criteria for salvage prostate HDR brachytherapy
      combined with interstitial hyperthermia were biopsy confirmed local recurrence
      and absence of nodal and distant metastases. All patients were treated with a
      dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia
      procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to
      heat the prostate to 41-43  degrees C for 60 min. Toxicity for the organs of the
      genitourinary system and rectum was assessed according to the Common Terminology
      Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent
      biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml).
      RESULTS: The median age was 71 years (range 62-83 years), the median initial PSA
      level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was
      2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48
      months). The combination of HDR brachytherapy and IHT was well tolerated. The
      most frequent complications were nocturia, weak urine stream, urinary frequency,
      hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No
      grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate
      of biochemical control after salvage treatment was 74 %. The PSA in 20 patients
      decreased below the presalvage level, while 11 patients achieved a PSA nadir <
      0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced
      biochemical failure, bone metastases were found in 2 patients. CONCLUSION: IHT in
      combination with salvage HDR brachytherapy is a well tolerated and effective
      treatment.

PMID- 24317193
TI  - Place of death and end-of-life transitions experienced by very old people with
      differing cognitive status: retrospective analysis of a prospective population
      based cohort aged 85 and over.
AB  - BACKGROUND: Despite fast-growing 'older old' populations, 'place of care'
      trajectories for very old people approaching death with or without dementia are
      poorly described and understood. AIM: To explore end-of-life transitions of
      'older old' people across the cognitive spectrum. DESIGN: Population-based
      prospective cohort (United Kingdom) followed to death. SETTING/PARTICIPANTS:
      Mortality records linked to 283 Cambridge City over-75s Cohort participants'
      cognitive assessments <1 year before dying aged >= 85 years. RESULTS: Overall,
      69% were community dwelling in the year before death; of those with severe
      cognitive impairment 39% were community dwelling. Only 6% subsequently changed
      their usual address. However, for 55% their usual address on death registration
      was not their place of death. Dying away from the 'usual address' was associated
      with cognition, overall fewer moving with increasing cognitive impairment -
      cognition intact 66%, mildly/moderately impaired 55% and severely impaired 42%,
      trend p = 0.003. This finding reflects transitions being far more common from the
      community than from institutions: 73% from the community and 28% from
      institutions did not die where last interviewed (p < 0.001). However, severely
      cognitively impaired people living in the community were the most likely group of
      all to move: 80% (68%-93%). Hospitals were the most common place of death except
      for the most cognitively impaired, who mostly died in care homes. CONCLUSION:
      Most very old community-dwelling individuals, especially the severely cognitively
      impaired, died away from home. Findings also suggest that long-term care may play
      a role in avoidance of end-of-life hospital admissions. These results provide
      important information for planning end-of-life services for older people across
      the cognitive spectrum, with implications for policies aimed at supporting home
      deaths. MESH TERMS: Cognitive impairment, Dementia, Aged, 80 and over, Aged,
      frail elderly, Patient Transfer, Residential characteristics, Homes for the aged,
      Nursing Homes, Delivery of Health Care, Terminal care Other key phrases: Older
      old, Oldest old, Place of death, Place of care, End-of-life care.

PMID- 24317194
TI  - Assessment of anti-inflammatory effect of 5beta-hydroxypalisadin B isolated from
      red seaweed Laurencia snackeyi in zebrafish embryo in vivo model.
AB  - 5beta-Hydroxypalisadin B, a halogenated secondary metabolite isolated from red
      seaweed Laurencia snackeyi was evaluated for its anti-inflammatory activity in
      lipopolysaccharide (LPS)-induced zebrafish embryo. Preliminary studies suggested
      the effective concentrations of the compound as 0.25, 0.5, 1 MUg/mL for further
      in vivo experiments. 5beta-Hydroxypalisadin B, exhibited profound protective
      effect in the zebrafish embryo as confirmed by survival rate, heart beat rate,
      and yolk sac edema size. The compound acts as an effective agent against reactive
      oxygen species (ROS) formation induced by LPS and tail cut. Moreover, 5beta
      hydroxypalisadin B effectively inhibited the LPS-induced nitric oxide (NO)
      production in zebrafish embryo. All the tested protective effects of 5beta
      hydroxypalisadin B were comparable to the well-known anti-inflammatory agent
      dexamethasone. According to the results obtained, 5beta-hydroxypalisadin B
      isolated from red seaweed L. snackeyi could be considered as an effective anti
      inflammatory agent which might be further developed as a functional ingredient.

PMID- 24317195
TI  - Thermal stability of quadruplex primers for highly versatile isothermal DNA
      amplification.
AB  - Quadruplex priming amplification (QPA) allows isothermal amplification of nucleic
      acids with improved yield and simplified detection. This assay is based on a DNA
      quadruplex, GGGTGGGTGGGTGGG (G3T), which in the presence of specific cations
      possesses unusually high thermal stability. QPA employs truncated G3T sequences
      as primers, which upon polymerase elongation, self-dissociate from the binding
      site and allow the next round of priming without thermal unfolding of amplicons.
      The rate of amplification strongly depends on the thermal stability of the
      primer/primer binding site (PBS) complex and to date QPA has been demonstrated to
      work over a narrow temperature range. To expand the capabilities of QPA, in the
      present study, we studied the fold and thermodynamic properties of the wild-type
      G3T and variants containing sequence modifications or extensions at the 5'-end.
      Circular dichroism studies demonstrate that the substitution of thymidines by
      other nucleotides or GC addition at the 5'-end does not change the parallel fold
      of G3T. Thermal unfolding experiments revealed that purine bases incorporated at
      loop positions and 5'-end dinucleotide extension significantly destabilize the
      quadruplex, while loop pyrimidines have almost no effect. Overall, the results of
      these studies suggest that linear isothermal QPA can be performed over a wide
      temperature range to accommodate both thermophilic and mesophilic DNA
      polymerases. 

PMID- 24317197
TI  - Retraction: High Mobility Group A1 (HMGA1) proteins interact with p53 and inhibit
      its apoptotic activity.

PMID- 24317196
TI  - Exploring the energetics of histone H1.1 and H1.4 duplex DNA interactions.
AB  - H1.1 and H1.4 bind tightly to both short DNA oligomers and to CT-DNA
      (Ka~1*10(7)). Binding is accompanied by an unfavorable enthalpy change (?H~+22
      kcal/mol) and a favorable entropy change (-T?S~-30 kcal/mol). The Tm for the
      H1.4/CT-DNA complex is increased by 9  degrees C over the Tm for the free DNA.
      H1.4 titrations of the DNA oligomers yield stoichiometries (H1/DNA) of 0.64,
      0.96, 1.29, and 2.04 for 24, 36, 48, and 72-bp DNA oligomers. The stoichiometries
      are consistent with a binding site size of 37+/-1 bp. CT-DNA titration data are
      consistent with binding site sizes of 32 bp for H1.1 and 36 bp for H1.4. The heat
      capacity changes, DeltaCp, for formation of the H1.1 and H1.4/CT-DNA complexes
      are -160 cal mol(-1) K(-1) and -192 cal mol(-1)K(-1) respectively. The large
      negative DeltaCp values indicate the loss of water from the protein DNA interface
      in the complex.

PMID- 24317198
TI  - Acid sphingomyelinase determines melanoma progression and metastatic behaviour
      via the microphtalmia-associated transcription factor signalling pathway.
AB  - Melanoma is a rapidly growing and highly metastatic cancer with high mortality
      rates, for which a resolutive treatment is lacking. Identification of novel
      therapeutic strategies and biomarkers of tumour stage is thus of particular
      relevance. We report here on a novel biomarker and possible candidate therapeutic
      target, the sphingolipid metabolising enzyme acid sphingomyelinase (A-SMase). A
      SMase expression correlates inversely with tumour stage in human melanoma
      biopsies. Studies in a mouse model of melanoma and on cell lines derived from
      mouse and human melanomas demonstrated that A-SMase levels of expression actually
      determine the malignant phenotype of melanoma cells in terms of pigmentation,
      tumour progression, invasiveness and metastatic ability. The action of A-SMase is
      mediated by the activation of the extracellular signal-regulated kinase, the
      subsequent proteasomal degradation of the Microphtalmia-associated transcription
      factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met,
      downstream targets of Mitf involved in tumour cell proliferation, survival and
      metastatisation. 

PMID- 24317199
TI  - Autophagy is required for zebrafish caudal fin regeneration.
AB  - Regeneration is the ability of multicellular organisms to replace damaged tissues
      and regrow lost body parts. This process relies on cell fate transformation that
      involves changes in gene expression as well as in the composition of the
      cytoplasmic compartment, and exhibits a characteristic age-related decline. Here,
      we present evidence that genetic and pharmacological inhibition of autophagy - a
      lysosome-mediated self-degradation process of eukaryotic cells, which has been
      implicated in extensive cellular remodelling and aging - impairs the regeneration
      of amputated caudal fins in the zebrafish (Danio rerio). Thus, autophagy is
      required for injury-induced tissue renewal. We further show that upregulation of
      autophagy in the regeneration zone occurs downstream of mitogen-activated protein
      kinase/extracellular signal-regulated kinase signalling to protect cells from
      undergoing apoptosis and enable cytosolic restructuring underlying terminal cell
      fate determination. This novel cellular function of the autophagic process in
      regeneration implies that the role of cellular self-digestion in differentiation
      and tissue patterning is more fundamental than previously thought. 

PMID- 24317200
TI  - Delayed innocent bystander cell death following hypoxia in Caenorhabditis
      elegans.
AB  - After hypoxia, cells may die immediately or have a protracted course, living or
      dying depending on an incompletely understood set of cell autonomous and
      nonautonomous factors. In stroke, for example, some neurons are thought to die
      from direct hypoxic injury by cell autonomous primary mechanisms, whereas other
      so called innocent bystander neurons die from factors released from the primarily
      injured cells. A major limitation in identifying these factors is the inability
      of current in vivo models to selectively target a set of cells for hypoxic injury
      so that the primarily injured cells and the innocent bystanders are clearly
      delineated. In order to develop such a model, we generated transgenic
      Caenorhabditis elegans strains where 2-3% of somatic cells were made selectively
      sensitive to hypoxia. This was accomplished by cell type-specific wild-type
      rescue in either pharyngeal myocytes or GABAergic neurons of a hypoxia resistance
      producing translation factor mutation. Surprisingly, hypoxic targeting of these
      relatively small subsets of non-essential cells produced widespread innocent
      bystander cell injury, behavioral dysfunction and eventual organismal death. The
      hypoxic injury phenotypes of the myocyte or neuron sensitized strains were
      virtually identical. Using this model, we show that the C. elegans insulin
      receptor/FOXO transcription factor pathway improves survival when activated only
      after hypoxic injury and blocks innocent bystander death. 

PMID- 24317202
TI  - Ictal swearing: a case series and review.
AB  - Seizures can manifest with ictal swearing but few studies have investigated the
      localising value of this epileptic manifestation. In this case series and review
      of the literature, we attempted to determine whether ictal swearing could help
      localise the epileptic focus. We review two previously published cases and report
      eight additional epileptic patients with ictal swearing for whom the epileptic
      focus was determined based on clinical, structural, electrophysiological, and
      surgical outcome data. Results indicated that ictal swearing occurs more commonly
      in male subjects and lateralises to the non-dominant hemisphere, but has poor
      localisation value, arising either from the frontal, parietal, temporal or
      occipital lobes in different patients. We discuss the significance of these
      findings. [Published with video sequences]. 

PMID- 24317201
TI  - Phospholipase D-mediated autophagic regulation is a potential target for cancer
      therapy.
AB  - Autophagy is a catabolic process in which cell components are degraded to
      maintain cellular homeostasis by nutrient limitations. Defects of autophagy are
      involved in numerous diseases, including cancer. Here, we demonstrate a new role
      of phospholipase D (PLD) as a regulator of autophagy. PLD inhibition enhances
      autophagic flux via ATG1 (ULK1), ATG5 and ATG7, which are essential autophagy
      gene products critical for autophagosome formation. Moreover, PLD suppresses
      autophagy by differentially modulating phosphorylation of ULK1 mediated by mTOR
      and adenosine monophosphate-activated protein kinase (AMPK), and by suppressing
      the interaction of Beclin 1 with vacuolar-sorting protein 34 (Vps34), indicating
      that PLD coordinates major players of the autophagic pathway, AMPK-mTOR-ULK1 and
      Vps34/Beclin 1. Ultimately, PLD inhibition significantly sensitized in vitro and
      in vivo cancer regression via genetic and pharmacological inhibition of
      autophagy, providing rationale for a new therapeutic approach to enhancing the
      anticancer efficacy of PLD inhibition. Collectively, we show a novel role for PLD
      in the molecular machinery regulating autophagy. 

PMID- 24317204
TI  - Real-time detection of gastric insufflation related to facemask pressure
      controlled ventilation using ultrasonography of the antrum and epigastric
      auscultation in nonparalyzed patients: a prospective, randomized, double-blind
      study.
AB  - BACKGROUND: The authors sought to determine the level of inspiratory pressure
      minimizing the risk of gastric insufflation while providing adequate pulmonary
      ventilation. The primary endpoint was the increase in incidence of gastric
      insufflation detected by ultrasonography of the antrum while inspiratory pressure
      for facemask pressure-controlled ventilation increased from 10 to 25 cm H2O.
      METHODS: In this prospective, randomized, double-blind study, patients were
      allocated to one of the four groups (P10, P15, P20, and P25) defined by the
      inspiratory pressure applied during controlled-pressure ventilation: 10, 15, 20,
      and 25 cm H2O. Anesthesia was induced using propofol and remifentanil; no
      neuromuscular-blocking agent was administered. Once loss of eyelash reflex
      occurred, facemask ventilation was started for a 2-min period while gastric
      insufflation was detected by auscultation and by real-time ultrasonography of the
      antrum. The cross-sectional antral area was measured using ultrasonography before
      and after facemask ventilation. Respiratory parameters were recorded. RESULTS:
      Sixty-seven patients were analyzed. The authors registered statistically
      significant increases in incidences of gastric insufflation with inspiratory
      pressure, from 0% (group P10) to 41% (group P25) according to auscultation, and
      from 19 to 59% according to ultrasonography. In groups P20 and P25, detection of
      gastric insufflation by ultrasonography was associated with a statistically
      significant increase in the antral area. Lung ventilation was insufficient for
      group P10. CONCLUSION: Inspiratory pressure of 15 cm H2O allowed for reduced
      occurrence of gastric insufflation with proper lung ventilation during induction
      of anesthesia with remifentanil and propofol in nonparalyzed and nonobese
      patients. (Anesthesiology 2014; 120:326-34).

PMID- 24317205
TI  - Anesthesiologists and the transformation of the healthcare system: a call to
      action.

PMID- 24317203
TI  - Connexin-dependent gap junction enhancement is involved in the synergistic effect
      of sorafenib and all-trans retinoic acid on HCC growth inhibition.
AB  - Increasing gap junction activity in tumor cells provides a target by which to
      enhance antineoplastic therapies. Previously, several naturally occurring agents,
      including all-trans retinoic acid (ATRA) have been demonstrated to increase gap
      junctional intercellular communication (GJIC) in a number of types of cancer
      cells. In the present study, we investigated in vitro whether ATRA modulates the
      response of human hepatocellular carcinoma (HCC) cells to sorafenib, the only
      proven oral drug for advanced HCC, and the underlying mechanisms. HepG2 and SMMC
      7721 cells were treated with sorafenib and/or ATRA, and cell proliferation and
      apoptosis were analyzed; the role of GJIC was also explored. We found that ATRA,
      at non-toxic concentrations, enhanced sorafenib-induced growth inhibition in both
      HCC cell lines, and this effect was abolished by two GJIC inhibitors, 18-alpha-GA
      and oleamide. Whereas lower concentrations of sorafenib (5 uM) or ATRA (0.1 or 10
      uM) alone modestly induced GJIC activity, the combination of sorafenib plus ATRA
      resulted in a strong enhancement of GJIC. However, the action paradigm differed
      in the HepG2 and SMMC-7721 cells, with the dominant effect of GJIC dependent on
      the cell-specific connexin increase in protein amounts and relocalization. RT-PCR
      assay further revealed a transcriptional modification of the key structural
      connexin in the two cell lines. Thus, a connexin-dependent gap junction
      enhancement may play a central role in ATRA plus sorafenib synergy in inhibiting
      HCC cell growth. Since both agents are available for human use, the combination
      treatment represents a future profitable strategy for the treatment of advanced
      HCC.

PMID- 24317206
TI  - Anesthesia quality and safety: advancing on a legacy of leadership.

PMID- 24317207
TI  - Facemask ventilation during induction of anesthesia: how "gentle" is "gentle"
      enough?

PMID- 24317208
TI  - Prevention of synkinesis by biofeedback therapy: a randomized clinical trial.
AB  - OBJECTIVE: The aim of present study was to find a better procedure to prevent
      synkinesis in facial nerve palsy. DESIGN: A randomized clinical trial. SETTING:
      Clinical rehabilitation faculty and general rehabilitation centers. SUBJECTS:
      Twenty- nine patients with facial nerve palsy were selected via electrodiagnosis
      tests. INTERVENTION: The experimental group (n = 16) was treated with biofeedback
      electromyography, whereas the control group (n = 13) received common
      physiotherapy. All patients received 1-year treatment. MAIN OUTCOME MEASURES:
      Evaluation of facial grading scale before and after treatment and severity of
      synkinesia. RESULTS: At the end of treatment, there was a rise in facial grading
      system in both groups compared with baseline (p < 0.05, paired t test). There
      were significant differences in the facial grading system between 2 groups at the
      end of the study, but the experimental group showed better result than the other
      one. The number of patients with synkinesis and the severity of their synkinesis
      in the experimental group were lesser than those of the control group.
      CONCLUSION: Biofeedback therapy is more efficient than common physiotherapy. By
      using this approach, controlling and reducing synkinesis is more feasible.

PMID- 24317209
TI  - Reversible cochlear function with ANCA-associated vasculitis initially diagnosed
      by otologic symptoms.
AB  - OBJECTIVE: To present 8 cases with hearing loss as an initial symptom of
      antineural cytoplasmic antibody (ANCA)-associated vasculitis (AAV) involving
      granulomatosis with polyangiitis (GPA) and to discuss the treatment and
      mechanisms of hearing outcomes after immunosuppressive therapy. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Eight
      patients were referred to our university hospital between 2004 and 2012 for
      intractable otitis media with acute progressive mixed (conductive and
      sensorineural) hearing loss and facial palsy. INTERVENTION(S): Diagnostics and
      treatment. MAIN OUTCOME MEASURES: Otologic symptoms as initial manifestations of
      otitis media with AAV and cochlear function after treatment. RESULTS: Eight cases
      (6 female and 2 male subjects; aged 54-73 yr; 6 MPO [myeloperoxidase]-ANCA
      positive and 2 PR3 [proteinase 3]-ANCA-positive cases) were included. Progressive
      hearing loss was present in all patients, and facial palsy was present in 5 of 8
      patients total. Patients with hearing levels better than 95 dB improved with good
      speech discrimination after immunosuppressive therapy, but the completely deaf
      could not be recovered. All patients have been successfully controlled for 1 to 8
      years without any systemic disorders. CONCLUSION: This study showed the
      difficulty of diagnosing localized AAV and the effectiveness of immunosuppressive
      therapy for hearing loss in the early stage. Based on these results, early-stage
      AAV would influence the stria vascularis in the cochlea. Otitis media with ANCA
      associated vasculitis is a new entity among the causes of intractable otitis
      media and progressive hearing loss.

PMID- 24317210
TI  - Safety of ultrasonic bone curette in ear surgery by measuring skull bone
      vibrations.
AB  - HYPOTHESIS: Mastoidectomy using an ultrasonic bone curette (UBC) is as safe for
      the inner ear as a mastoidectomy using a high-speed drill. BACKGROUND: Transcanal
      endoscopic ear surgery (TEES) is a minimally invasive, secure, and functional
      technique, which has been performed using high-speed drills. We have started to
      use a UBC instead of the high-speed drill because a UBC allows for simultaneous
      bone cutting, irrigation, and aspiration. These features of the UBC make it an
      excellent candidate for use in one-handed TEES, but the safety of the UBC still
      needs to be confirmed. We thus measured skull vibrations caused by the UBC to
      estimate the effects of UBC on the inner ear. METHODS: Eight patients with
      cholesteatoma underwent mastoidectomy using a Sonopet UST-2001 UBC (Stryker, MI,
      USA) and 2 high-speed drills (drills A and B). Skull vibrations were measured
      using polyvinylidene difluoride film taped to the forehead as a piezoelectric
      vibration sensor. The recorded data were transformed to the power spectrum in the
      frequency domain by fast Fourier transform. The mean and peak values of
      vibrations were analyzed in four frequency bands: 200 to 500 Hz, 500 to 2,000 Hz,
      2,000 to 8,000 Hz, and 8,000 Hz to 20 kHz. RESULTS: Both the mean values and the
      peak values of skull vibrations caused by the UBC were significantly smaller than
      those values obtained for drill B between 500 and 8,000 Hz, (p < 0.05). No
      significant differences were found among the 3 instruments below 500 Hz or above
      8,000 Hz. CONCLUSION: Skull vibration levels generated by the UBC were found to
      be comparable or even lower than those levels associated with conventional high
      speed drills. These findings indicated that the UBC can be safely applied to TEES
      without the risk of harmful effects on the inner ear.

PMID- 24317211
TI  - Round window electrocochleography just before cochlear implantation: relationship
      to word recognition outcomes in adults.
AB  - HYPOTHESES: Electrocochleography (ECoG) to acoustic stimuli can differentiate
      relative degrees of cochlear responsiveness across the population of cochlear
      implant recipients. The magnitude of the ongoing portion of the ECoG, which
      includes both hair cell and neural contributions, will correlate with speech
      outcomes as measured by results on CNC word score tests. BACKGROUND:
      Postoperative speech outcomes with cochlear implants vary from almost no benefit
      to near normal comprehension. A factor expected to have a high predictive value
      is the degree of neural survival. However, speech performance with the implant
      does not correlate with the number and distribution of surviving ganglion cells
      when measured postmortem. We will investigate whether ECoG can provide an
      estimate of cochlear function that helps predict postoperative speech outcomes.
      METHODS: An electrode was placed at the round window of the ear about to be
      implanted during implant surgery. Tone bursts were delivered through an insert
      earphone. Subjects included children (n = 52, 1-18 yr) and postlingually hearing
      impaired adults (n = 32). Word scores at 6 months were available from 21 adult
      subjects. RESULTS: Significant responses to sound were recorded from almost all
      subjects (80/84 or 95%). The ECoG magnitudes spanned more than 50 dB in both
      children and adults. The distributions of ECoG magnitudes and frequencies were
      similar between children and adults. The correlation between the ECoG magnitude
      and word score accounted for 47% of the variance. CONCLUSION: ECoGs with high
      signal-to-noise ratios can be recorded from almost all implant candidates,
      including both adult and pediatric populations. In postlingual adults, the ECoG
      magnitude is more predictive of implant outcomes than other nonsurgical variables
      such as duration of deafness or degree of residual hearing.

PMID- 24317212
TI  - Silicone-coated thin film array cochlear implantation in a feline model.
AB  - OBJECTIVES: Some limitations of cochlear implants can be attributed to a
      restricted spectral representation of sound provided by contemporary electrode
      arrays. Microfabricated high-density thin film array (TFA) technology enables a
      greater density of stimulating sites and, thus, a more complete spectral
      representation. Previous pilot cadaveric studies have documented insertion
      characteristics, although not electrical characteristics. STUDY DESIGN: Electrode
      evoked auditory brainstem response (ABR) testing in a feline model. METHODS: Six
      healthy, normal hearing cats were unilaterally deafened and implanted with a
      silicone coated TFA, measuring 27.8 * 0.4 * 80MUm (L * W * H). Monopolar
      stimulation of single electrodes was used to evoke a triple peaked ABR.
      Thresholds to evoke a minimal ABR were determined. RESULTS: All 6 cats underwent
      successful full insertion and activation. Thresholds to evoke minimal ABR's
      varied among implants ranging from 75 to 450 MUA. Over the basal portion of the
      array, thresholds were either larger or unable to evoke an ABR. CONCLUSION: Two
      thirds of the implants showed ABR's along the entire array, whereas the others
      evoked ABR's at the apical end and less robustly more basally. This may reflect
      increased distance of the electrodes from the modiolus, as the basal half of the
      array is narrower relative to the width of the scala. A tapered design to ensure
      array distance to modiolus is minimized may enable the basal half of the arrays
      to stimulate more consistently.

PMID- 24317213
TI  - Contralateral reinnervation in patients with facial nerve palsy.
AB  - OBJECTIVE: To demonstrate a phenomenon of contralateral reinnervation in facial
      nerve palsy patients. METHODS: Retrospective case review of 9 patients whose
      facial muscles were electrophysiologically proven to be reinnervated
      contralaterally. RESULTS: The duration from symptom onset spanned from 3 to 114
      months. All subjects had moderate-to-severe facial palsy initially. Contralateral
      reinnervation was observed in both traumatic and idiopathic causes, also in both
      complete and incomplete palsies. Cross-innervation is more frequently reported in
      muscles near the midline; however, this is the first report demonstrating
      evidence of cross-innervation in muscles far from the midline--the frontalis, the
      orbicularis oculi, and the zygomaticus. CONCLUSION: Although contralateral
      reinnervation after facial nerve palsy is a common observation, it has not gained
      appropriate attention. Without recognition of this phenomenon, misinterpretation
      of the electromyography may mislead the proper timing of nerve repair or
      reanimation procedure. Therefore, routine examination of motor action potential
      by contralateral stimulation during electromyography, especially in patients with
      moderate-to-severe palsy, would provide accurate assessment of the injured nerves
      and would help in appropriate decision making for further treatment.

PMID- 24317214
TI  - Blind sac closure of the external auditory canal for chronic middle ear disease.
AB  - OBJECTIVE: To determine the rate of complications in patients who underwent blind
      sac closure of the external auditory canal for chronic middle ear disease. STUDY
      DESIGN AND SETTING: Retrospective case review of 29 patients from combined public
      tertiary and private centers who underwent blind sac closure between 2000 and
      2011. PATIENTS: All patients undergoing blind sac closure with minimum follow-up
      period of 1 year were included. There were 14 male and 15 female subjects with a
      mean age of 54 years at time of surgery. MAIN OUTCOME MEASURE: Complications were
      identified as major and minor complications, with particular attention to the
      rate of residual cholesteatoma. RESULTS: Thirty-two cases of blind sac closure
      were identified in 29 patients, with 3 patients undergoing bilateral procedures.
      We identified 8 major and 6 minor complications. Of the major complications, 3
      were infections, and 5 involved residual cholesteatoma. Recurrent cholesteatoma
      was identified between 2 years 8 months and 6 years 6 months. CONCLUSION:
      Although blind sac closure of the external ear canal is a functionally useful
      procedure, it is associated with a significant rate of complications. In
      particular, we noted a higher rate of residual cholesteatoma in our series, when
      compared with the published literature. Appropriate patient selection to ensure
      long-term follow-up compliance for at least 8 years is essential for the
      detection of recurrent cholesteatoma.

PMID- 24317215
TI  - Sequential multipoint motion of the tympanic membrane measured by laser Doppler
      vibrometry: preliminary results for normal tympanic membrane.
AB  - BACKGROUND: Numerous studies have reported sound-induced motion of the tympanic
      membrane (TM). To demonstrate sequential motion characteristics of the entire TM
      by noncontact laser Doppler vibrometry (LDV), we have investigated multipoint TM
      measurement. MATERIALS AND METHODS: A laser Doppler vibrometer was mounted on a
      surgical microscope. The velocity was measured at 33 points on the TM using
      noncontact LDV without any reflectors. Measurements were performed with tonal
      stimuli of 1, 3, and 6 kHz. Amplitudes were calculated from these measurements,
      and time-dependent changes in TM motion were described using a graphics
      application. RESULTS: TM motions were detected more clearly and stably at 1 and 3
      kHz than at other frequencies. This is because the external auditory canal acted
      as a resonant tube near 3 kHz. TM motion displayed 1 peak at 1 kHz and 2 peaks at
      3 kHz. Large amplitudes were detected in the posterosuperior quadrant (PSQ) at 1
      kHz and in the PSQ and anteroinferior quadrant (AIQ) at 3 kHz. The entire TM
      showed synchronized movement centered on the PSQ at 1 kHz, with phase-shifting
      between PSQ and AIQ movement at 3 kHz. Amplitude was smaller at the umbo than at
      other parts. In contrast, amplitudes at high frequencies were too small and
      complicated to detect any obvious peaks. CONCLUSION: Sequential multipoint motion
      of the tympanic membrane showed that vibration characteristics of the TM differ
      according to the part and frequency.

PMID- 24317216
TI  - The bone conduction implant--first implantation, surgical and audiologic aspects.
AB  - OBJECTIVE: To report on preoperative assessment, surgery, and audiologic outcome
      of the first patient implanted with the bone conduction implant (BCI).
      BACKGROUND: The BCI is a bone conduction hearing device with an intact skin
      solution where the transducer is implanted close to the ear canal opening. By
      avoiding a percutaneous screw attachment to the skull, the BCI is anticipated to
      reduce complications associated with the Bone-Anchored Hearing Aid (BAHA)
      solution. METHODS: The first patient to receive a BCI was a 42-year-old woman
      with a unilateral mixed hearing loss due to tympanosclerosis. Preoperative and
      postoperative cone beam computed tomography and a virtual planning tool for 3D
      reconstruction were used to optimize and control the position of the BCI in the
      mastoid. The transducer was placed in a 5-mm deep seating in the mastoid and
      secured with a titanium bar. Free field tone and speech audiometry were conducted
      to evaluate the audiologic outcome at baseline (1 month postoperatively) and 1
      month after baseline. RESULTS: The BCI was placed in the position according to
      the preoperative 3D planning. On average, the tone thresholds improved by 30 dB,
      speech reception thresholds by 25.5 dB and speech signal-to-noise ratio by 9.7
      dB. The surgical procedure was considered simple and safe. CONCLUSION: The BCI
      can be implanted by a safe and easy surgical procedure. 3D preoperative planning
      can be helpful to optimize the BCI position. The BCI is a realistic alternative
      to the BAHA.

PMID- 24317217
TI  - Non-EPI DW MRI in planning the surgical approach to primary and recurrent
      cholesteatoma.
AB  - OBJECTIVE: To investigate a correlation between preoperative non-echo planar
      diffusion-weighted magnetic resonance imaging (non-EPI DW MRI) with surgical
      findings of localization and extension of cholesteatoma and to develop criteria
      for surgical planning. PATIENTS: Preoperative non-EPI DWMRI was available and
      positive for cholesteatoma in 27 patients with primary and 23 with
      residual/recurrent lesions. INTERVENTIONS: Patients with cholesteatoma limited to
      the middle ear and its extensions were managed with a transcanal endoscopic
      approach. Patients with extension of the cholesteatoma posteriorly to the lateral
      semicircular canal underwent retroauricular mastoidectomy combined with an
      endoscopic approach. MAIN OUTCOME MEASURE: Comparison of preoperative radiologic
      to surgical findings. RESULTS: DWI showed isolated tympanic and attic extension
      in 33 cases and attico-antral and mastoid extension in 17 cases. MRI findings
      correlated with surgical findings in all patients with primary cholesteatoma, 19
      of whom were managed with a transcanal endoscopic approach and 8 with endoscope
      assisted ear surgery. The transcanal endoscopic approach was applied in 14 of the
      patients with residual/recurrent cholesteatoma, and the other 9
      residual/recurrent lesions were eradicated using endoscope-assisted
      mastoidectomy. DWI overestimated cholesteatoma sites in 1 patient with residual
      lesion. The smallest cholesteatoma detected on DWI was a 3-mm lesion in the
      middle ear over the facial nerve. CONCLUSION: Primary and residual/recurrent
      cholesteatoma was accurately detected on non-EPI DWI with 98% clinical and
      radiologic concordance. Lesions less than 8 mm confined to the middle ear and its
      extensions can be eradicated with a minimally invasive endoscopic transcanal
      technique, whereas endoscope-assisted retroauricular mastoidectomy is preferred
      for larger lesions.

PMID- 24317218
TI  - Response to letter to the editor concerning: Bone-anchored hearing implant
      loading at three weeks: stability and tolerability after six months.

PMID- 24317219
TI  - Facial reanimation surgery restores affect display.
AB  - OBJECTIVE: Assess the ability of facial reanimation surgery to restore affect
      display in patients with severe facial paralysis. STUDY DESIGN: Survey of healthy
      observers' perception of change in facial visage from preoperative to
      postoperative state. SETTING: Academic tertiary referral center. MAIN OUTCOME
      MEASURES: Observer graded affect display. METHODS: Ninety naive observers
      completed a survey with pictures of paralyzed faces, smiling and in repose,
      before and after surgery, as well as normal comparison faces. Observers
      characterized affect display of each face coded in primary affects from the
      Derogatis Affects Balance Scale. Results were analyzed with latent class analysis
      and regression using a three-class model. RESULTS: Preoperatively, paralyzed
      faces in repose were most likely to be considered negative (56.0%), then neutral
      (41.3%) and positive (2.7%). In this same cohort of patients in repose,
      reanimation surgery restored affect display to normal levels: decreasing negative
      classification (18.9%) and increasing neutral (53.4%) and positive (27.7%)
      classification. Hypothesis testing revealed no statistically significant
      differences in the mean classification probabilities for postoperative faces in
      repose versus normal faces in repose. The same analysis was performed for smiling
      faces, which showed marked improvement with reanimation surgery: decreasing
      negative (45.6%-11.7%) and increasing positive (26.2%-60.0%) classification.
      Despite this improvement, there were statistically significant differences in
      classification of postoperative smiling faces versus normal smiling faces.
      CONCLUSION: Facial reanimation surgery was associated with normalized affect
      display for faces in repose and improved affect display for smiling faces. These
      results provide evidence that facial reanimation improves the facial expression
      of emotion. Further assessment in additional contexts will help better
      characterize the ability of facial reanimation to mitigate the psychosocial
      burden associated with facial paralysis.

PMID- 24317221
TI  - Lithographically defined porous Ni-carbon nanocomposite supercapacitors.
AB  - Ni was deposited onto lithographically-defined conductive three dimensional
      carbon networks to form asymmetric pseudo-capacitive electrodes. A real capacity
      of above 500 mF cm(-2), or specific capacitance of ~2100 F g(-1) near the
      theoretical value, has been achieved. After a rapid thermal annealing process,
      amorphous carbon was partially converted into multilayer graphene depending on
      the annealing temperature and time duration. These annealed Ni-graphene composite
      structures exhibit enhanced charge transport kinetics relative to un-annealed Ni
      carbon scaffolds indicated by a reduction in peak separation from 0.84 V to 0.29
      V at a scan rate of 1000 mV s(-1). 

PMID- 24317220
TI  - Prosthetic implantation of the human vestibular system.
AB  - HYPOTHESIS: A functional vestibular prosthesis can be implanted in human such
      that electrical stimulation of each semicircular canal produces canal-specific
      eye movements while preserving vestibular and auditory function. BACKGROUND: A
      number of vestibular disorders could be treated with prosthetic stimulation of
      the vestibular end organs. We have previously demonstrated in rhesus monkeys that
      a vestibular neurostimulator, based on the Nucleus Freedom cochlear implant, can
      produce canal-specific electrically evoked eye movements while preserving
      auditory and vestibular function. An investigational device exemption has been
      obtained from the FDA to study the feasibility of treating uncontrolled Meniere's
      disease with the device. METHODS: The UW/Nucleus vestibular implant was implanted
      in the perilymphatic space adjacent to the three semicircular canal ampullae of a
      human subject with uncontrolled Meniere's disease. Preoperative and postoperative
      vestibular and auditory function was assessed. Electrically evoked eye movements
      were measured at 2 time points postoperatively. RESULTS: Implantation of all
      semicircular canals was technically feasible. Horizontal canal and auditory
      function were largely, but not totally, lost. Electrode stimulation in 2 of 3
      canals resulted in canal-appropriate eye movements. Over time, stimulation
      thresholds increased. CONCLUSION: Prosthetic implantation of the semicircular
      canals in humans is technically feasible. Electrical stimulation resulted in
      canal-specific eye movements, although thresholds increased over time.
      Preservation of native auditory and vestibular function, previously observed in
      animals, was not demonstrated in a single subject with advanced Meniere's
      disease.

PMID- 24317222
TI  - How bone tissue and cells experience elevated temperatures during orthopaedic
      cutting: an experimental and computational investigation.
AB  - During orthopaedic surgery elevated temperatures due to cutting can result in
      bone injury, contributing to implant failure or delayed healing. However, how
      resulting temperatures are experienced throughout bone tissue and cells is
      unknown. This study uses a combination of experiments (forward-looking infrared
      (FLIR)) and multiscale computational models to predict thermal elevations in bone
      tissue and cells. Using multiple regression analysis, analytical expressions are
      derived allowing a priori prediction of temperature distribution throughout bone
      with respect to blade geometry, feed-rate, distance from surface, and cooling
      time. This study offers an insight into bone thermal behavior, informing
      innovative cutting techniques that reduce cellular thermal damage. 

PMID- 24317223
TI  - Ruthenium-catalyzed ortho-C-H halogenations of benzamides.
AB  - [Ru3(CO)12] and AgO2C(1-Ad) enabled the first ruthenium-catalyzed intermolecular
      halogenations of arenes via C-H activation. Thereby, brominations and iodinations
      of electron-rich and electron-deficient benzamides were achieved in a highly
      selective fashion. 

PMID- 24317224
TI  - Dietary exposure of American kestrels (Falco sparverius) to decabromodiphenyl
      ether (BDE-209) flame retardant: uptake, distribution, debromination and
      cytochrome P450 enzyme induction.
AB  - Accumulation and evidence of debromination of the flame retardant
      2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) have been reported for
      biota, including raptorial birds, based on PBDE congener residues in tissues and
      eggs. However, in vivo studies with BDE-209-exposed birds are rare and unknown
      for a raptorial species. In the present study, males (n=22) of raptorial American
      kestrels (Falco sparverius) were exposed to 116,000ng of BDE-209 (high purity,
      >98%; in safflower oil) per day for 21days (~2,436,000ng total BDE-209 exposure
      over this uptake period), followed by a 25-day depuration period. Control males
      (n=11) received the safflower vehicle only. In the exposed birds, BDE-209 was
      quantifiable in all plasma (end of uptake and depuration period) as well as liver
      and fat (end of depuration only) samples. The mean (+/-SE) BDE-209 level in
      plasma was 1474+/-1145ng/g wet weight (ww) at the end of the uptake period, and
      was significantly (p<0.001) lower (88%) at 174+/-148ng/g ww after the 25day
      depuration period. This equates to a mean reduction rate of 52ng/g ww per day and
      a rough estimation of the BDE-209 half-life in plasma of approximately 14days.
      The mean (+/-SE) BDE-209 levels were 4668+/-6192ng/g ww in the fat, and 338+/
      311ng/g ww in the liver, of exposed individuals, which were significantly
      (p<=0.001) greater than mean concentrations (25+/-20 in fat and 2.6+/-0.9ng/g ww
      in liver) in the control birds. In addition to BDE-209, lower brominated PBDE
      congeners, and mainly meta- and para-debromination products of BDE-209 were also
      quantified in plasma, liver and/or fat. We estimated based on the dose that at
      least 80% of the non-BDE-209 concentration in the kestrel tissues and plasma must
      be derived from BDE-209 debromination by the kestrels. Where quantifiable, lower
      brominated PBDE concentrations were significantly (0.023>p>0.001) higher in the
      exposed relative to the control bird samples (except for BDE-154 and -153 in
      fat). Additional PBDE congeners found in plasma included nona-BDEs (208, 207 and
      206), followed by octa-BDEs (197, 196, 201 and 203), and in liver and/or fat, the
      hepta-BDEs 180 and 183 and BDE-153. Higher hepatic EROD activity (cytochrome P450
      1A1 monooxygenase-mediation) in the exposed birds compared to control birds was
      strongly suggested to be PBDE-induced, and was consistent with BDE-209 and
      congener metabolism in the exposed kestrels. The mean EROD activity rate was
      36.1pmol/min/mg protein relative to the (n=4) control birds whose activity was
      just above the detection limit (10.3pmol/min/mg protein). Overall, the results
      demonstrated that following diet exposure of kestrels to high purity BDE-209,
      uptake occurred as well as BDE-209 degradation via debromination to lower
      brominated PBDE congeners. 

PMID- 24317225
TI  - In vitro tests aiding ecological risk assessment of ciprofloxacin, tamoxifen and
      cyclophosphamide in range of concentrations released in hospital wastewater and
      surface water.
AB  - Ciprofloxacin (CIP), tamoxifen (TAM) and cyclophosphamide (CP) which are often
      used in anticancer treatment are released in hospital effluent and into the
      environment. Although the concentrations are low (from ng/L to MUg/L), no data
      exist concerning their ecotoxicological impact. In this study two biomarkers of
      early effect were performed on hepatic cells (HepG2): cell viability and
      genotoxicity (DNA breaks) using cell proliferative assay and comet assay,
      respectively. These data were compared with two standardized ecotoxicological
      tests: algaltoxkit FTM and microtox(r). Cells were exposed to an increasing
      amount of an individual drug or in a mixture for 24, 48 or 72h. The time-exposure
      of bacteria and algae ranged between 5 and 30min and 72h, respectively. A non
      monotonic dose-response on cell viability was observed when HepG2 cells were
      exposed to TAM alone or in the presence of CIP. The same scheme was observed with
      microtox(r) when the bacteria were exposed to the mixtures. On the other side, an
      individual drug does not induce any DNA breaks on hepatic cells, whereas a
      mixture leads to a dose dependent increase of DNA breaks. Similarly a positive
      response was observed with algaltoxkit FTM only with mixtures. Synergistic
      effects observed when drugs are in a mixture highlight the importance of
      investigating the ecotoxicological effects of contaminants at low concentrations
      and in mixtures. 

PMID- 24317227
TI  - An assessment of residential exposure to environmental noise at a shipping port.
AB  - The World Health Organisation has recently acknowledged that contrary to the
      trend for other environmental stressors, noise exposure is increasing in Europe.
      However, little research has been conducted on environmental noise exposure to
      handling activity at shipping ports. This paper reports on research examining the
      extent of noise exposure for residents within the vicinity of Dublin Port,
      Ireland using the nation's largest port terminal as a proxy for port noise. In
      order to assess the level of exposure in the area, long-term measurements were
      undertaken at the most exposed residential facade for a period of 45days to
      determine the extent of night-time exposure that was above levels recommended by
      the World Health Organisation. The indicators L90, Leq and LMax were used to
      determine exposure levels. The results show that exposure is above night-time
      guideline limits set down by the WHO, above Irish levels for the assessment of
      noise mitigation and highlight the extent to which port noise can be a
      significant environmental stressor. The research also investigated the extent of
      low-frequency noise (which is associated with greater health issues) from night
      time port handling activity and found a significant low-frequency component
      indicating the negative health issues that might arise from port noise exposure
      more generally. We also undertook semi-structured interviews with residents to
      qualitatively assess the self-reported impact of prolonged night-time noise
      exposure for local residents. 

PMID- 24317226
TI  - Evaluation of pyrethroid exposures in pregnant women from 10 Caribbean countries.
AB  - Pyrethroid pesticides are commonly used in tropical regions such as the Caribbean
      as household insecticides, pet sprays, and where malaria is endemic, impregnated
      into mosquito-repellent nets. Of particular concern is exposure during pregnancy,
      as these compounds have the potential to cross the placental barrier and
      interfere with fetal development, as was shown in limited animal studies. The
      objective of this study was to evaluate exposure to pyrethroids to pregnant women
      residing in 10 English-speaking Caribbean countries. Pyrethroid exposures were
      determined by analyzing five pyrethroid metabolites in urine samples from 295
      pregnant women: cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA, and 4-F-3-PBA. Pyrethroid
      metabolite concentrations in Caribbean pregnant women were generally higher in
      the 10 Caribbean countries than levels reported for Canadian and U.S. women. In
      Antigua & Barbuda and Jamaica participants the geometric mean concentrations of
      cis-DBCA was significantly higher than in the other nine countries together
      (p<0.0001 and <0.0012 respectively). For cis- and trans-DCCA, only Antigua &
      Barbuda women differed significantly from participants of the other nine
      Caribbean countries (p<0.0001). Urinary 4-F-3-PBA and 3-PBA levels were
      significantly higher in Antigua & Barbuda (p<0.0028 and p<0.0001 respectively) as
      well as in Grenada (p<0.0001 and p<0.007 respectively). These results indicate
      extensive use of pyrethroid compounds such as permethrin and cypermethrin in
      Caribbean households. In Antigua & Barbuda, the data reveals a greater use of
      deltamethrin. This study underscores the need for Caribbean public health
      authorities to encourage their populations, and in particular pregnant women, to
      utilize this class of pesticides more judiciously given the potentially adverse
      effects of exposure on fetuses and infants. 

PMID- 24317229
TI  - Rapid cognitive and functional decline: Creutzfeldt-Jakob disease.
AB  - The emergence of "mad cow disease" has sparked interest in prion diseases,
      including Creutzfeldt-Jakob disease, a spongiform encephalopathy that can mimic
      other rapidly progressive dementias. A systematic approach to evaluation and
      diagnostic testing can help rule out other causes. 

PMID- 24317228
TI  - Effects of BDE-209 contaminated sediments on zebrafish development and potential
      implications to human health.
AB  - Polybrominated diphenyl ethers are compounds widely used as flame-retardants,
      which are of increasing environmental concern due to their persistence, and
      potential adverse effects. This study had two objectives. First, we assessed if
      BDE-209 in sediment was bioavailable and bioaccumulated into zebrafish embryos.
      Secondly, we assessed the potential impact on human and environmental health of
      bioavailable BDE-209 using human in vitro cell assays and zebrafish embryos.
      Zebrafish were exposed from 4h to 8days post-fertilization to sediments spiked
      with 12.5mg/kg of BDE-209. Zebrafish larvae accumulated ten fold more BDE-209
      than controls in unspiked sediment after 8days. BDE-209 impacted expression of
      neurological pathways and altered behavior of larvae, although BDE-209 had no
      visible affect on thyroid function or motoneuron and neuromast development.
      Zebrafish data and in silico predictions suggested that BDE-209 would also
      interact with key human transcription factors and receptors. We therefore tested
      these predictions using mammalian in vitro assays. BDE-209 activated human aryl
      hydrocarbon receptor, peroxisome proliferator activating receptors, CF/b-cat,
      activator protein 1, Oct-MLP, and the estrogen receptor-related alpha (ERRalpha)
      receptor in cell-based assays. BDE-209 also inhibited human acetylcholinesterase
      activity. The observation that BDE-209 can be bioaccumulated from contaminated
      sediment highlights the need to consider this as a potential environmental
      exposure route. Once accumulated, our data also show that BDE-209 has the
      potential to cause impacts on both human and environmental health. 

PMID- 24317230
TI  - Full characterization of the Cu-, Zn-, and Cd-binding properties of CnMT1 and
      CnMT2, two metallothioneins of the pathogenic fungus Cryptococcus neoformans
      acting as virulence factors.
AB  - We report here the full characterization of the metal binding abilities of CnMT1
      and CnMT2, two Cryptococcus neoformans proteins recently identified as
      metallothioneins (MTs), which have been shown to play a crucial role in the
      virulence and pathogenicity of this human-infecting fungus. In this work, we
      first performed a thorough in silico study of the CnMT1 and CnMT2 genes, cDNAs
      and corresponding encoded products. Subsequently, the Zn(II)-, Cd(II)- and Cu(I)
      binding abilities of both proteins were fully determined through the analysis of
      the metal-to-protein stoichiometries and the structural features (determined by
      ESI-MS, CD, ICP-AES and UV-vis spectroscopies) of the corresponding recombinant
      Zn-, Cd- and Cu-MT preparations synthesized in metal-enriched media. Finally, the
      analysis of the Zn/Cd and Zn/Cu replacement processes of the respective Zn-MT
      complexes when allowed to react with Cd(II) or Cu(I) aqueous solutions was
      performed. Comprehensive consideration of all gathered results allows us to
      consider both isoforms as genuine copper-thioneins, and led to the identification
      of unprecedented Cu5-core clusters in MTs. CnMT1 and CnMT2 polypeptides appear to
      be evolutionarily related to the small fungal MTs, probably by ancient tandem
      duplication events responding to a highly selective pressure to chelate copper,
      and far from the properties of Zn- and Cd-thioneins. Finally, we propose a
      modular structure of the Cu-CnMT1 and Cu-CnMT2 complexes on the basis of Cu5
      clusters, concordantly with the modular structure of the sequence of CnMT1 and
      CnMT2, constituted by three and five Cys-rich units, respectively.

PMID- 24317231
TI  - Novel use of noninvasive high-intensity focused ultrasonography for intercostal
      nerve neurolysis in a swine model.
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) is a noninvasive thermal
      ablation technique. High-intensity focused ultrasound has been used in small
      animal models to lesion neural tissue selectively. This study aimed to evaluate
      the efficacy of HIFU in a large-animal model for ablation of nerves similar in
      size to human nerves. METHODS: Twelve acute magnetic resonance-guided HIFU
      ablation lesions were created in intercostal nerves in a swine model. In a second
      pig, as a control, 4 radiofrequency ablation and 4 alcohol lesions were performed
      on intercostal nerves under ultrasound guidance. Preprocedural and postprocedural
      magnetic resonance imaging was then performed to evaluate radiologically the
      lesion size created by HIFU. Animals were euthanized 1 hour postprocedure, and
      necropsy was performed to collect tissue samples for histopathologic analysis.
      RESULTS: On gross and histological examination of the intercostal nerve, acute
      HIFU nerve lesions showed evidence of well-demarcated, acute, focally extensive
      thermal necrosis. Four intercostal nerves ablated with HIFU were sent for
      histopathologic analysis, with 2 of 4 lesions showing pathologic damage to the
      intercostal nerve. Similar results were shown with radiofrequency ablation
      technique, whereas the intercostal nerves appeared histologically intact with
      alcohol ablation. CONCLUSIONS: High-intensity focused ultrasound may be used as a
      noninvasive neurolytic technique in swine. High-intensity focused ultrasound may
      have potential as a neuroablation technique for patients with chronic and cancer
      pain.

PMID- 24317232
TI  - Ultrasound-guided single-penetration dual-injection block for leg and foot
      surgery: a prospective, randomized, double-blind study.
AB  - BACKGROUND AND OBJECTIVES: We describe a new approach to blocking the sciatic and
      saphenous nerves in the proximal thigh (level of the lesser trochanter or
      immediately below) using a single-penetration dual-injection (SPEDI) technique.
      The popliteal-sciatic approach necessitates repositioning of the leg exposing the
      popliteal fossa and an extra injection for the saphenous nerve (SAN) block at the
      midthigh level. We introduce an alternative, effective, and possibly faster
      method. METHODS: Sixty patients undergoing leg and foot surgery under general
      anesthesia were included. We deposited 15 mL of ropivacaine 0.75% around the
      sciatic nerve (SCN) and 5 mL of ropivacaine 0.75% at the SAN. Patients were
      randomized to the popliteal-sciatic/saphenous technique or the SPEDI technique.
      The primary outcome measure was performance time. Positioning time, pain
      assessment, nausea in the postanesthesia care unit, sufentanil demand, dermatomal
      anesthesia, and degree of motor blockade were also recorded. RESULTS: Performance
      time was significantly faster with the SPEDI technique (median time, 110 seconds
      [range, 57-315 seconds] vs 246 seconds [range, 163-472 seconds]; P < 0.0001).
      Positioning time was significantly shorter with the SPEDI technique (P < 0.0001).
      No other statistically significant differences were recorded. CONCLUSIONS: The
      SPEDI block resulted in significantly faster performance time and reduced
      positioning time with statistically equal efficacy in relation to pain
      assessment, nausea, sufentanil demand, dermatomal anesthesia, and motor blockade.
      The SPEDI block is statistically an equally effective alternative to the
      traditional popliteal-sciatic/saphenous block combination for leg and foot
      surgery, but it is faster, requires only 1 skin penetration, and does not require
      repositioning of the leg.

PMID- 24317233
TI  - Magnetic positioning system and ultrasound guidance for lumbar zygapophysial
      radiofrequency neurotomy: a cadaver study.
AB  - BACKGROUND AND OBJECTIVES: Chronic low back pain related to degenerative
      spondylosis is commonly managed by the radiofrequency ablation of sensory nerves.
      Fluoroscopic guidance has been considered mandatory to ensure placement of the
      active tip of the cannula parallel to the nerve to provide adequate neurolysis.
      Conversely, analgesic (or diagnostic) blockade is usually accomplished by placing
      the needle perpendicular to the nerve using either fluoroscopy or ultrasound (US)
      guidance. The recently introduced disposable equipment of internally cooled
      radiofrequency allows the denervation procedure to be performed similarly to the
      routine diagnostic block. Consequently, US may now potentially be used for image
      guided radiofrequency neurotomy. We sought to compare the accuracy using a novel
      US-based technique with the traditional fluoroscopy-guided placement. METHODS:
      The proof of concept study was performed using a magnetic positioning US-guided
      system. The precision of needle placements was compared with the standard
      fluoroscopic guidance. The primary outcome of this study was defined as the
      procedural accuracy. Procedural and radiation exposure time was also recorded. In
      addition, projected operational expenses were calculated. RESULTS: Ultrasound
      guided procedural accuracy reached 97%. Both the imaging and procedure times were
      similar between the 2 forms of imaging guidance. Of significant importance, the
      US-guided approach (no radiation exposure) was quantitatively advantageous over
      fluoroscopy-guidance, which required an average of 170 seconds of radiation per
      procedure. Thus, the US method seems to be cost effective. CONCLUSIONS: A
      magnetic positioning system allows accurate and quick US-guided placement of
      radiofrequency cannula to the desired anatomical targets, sparing patients and
      personnel from exposure to ionized radiation.

PMID- 24317234
TI  - Dexmedetomidine added to ropivacaine extends the duration of interscalene
      brachial plexus blocks for elective shoulder surgery when compared with
      ropivacaine alone: a single-center, prospective, triple-blind, randomized
      controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Research suggests that the addition of dexmedetomidine
      to local anesthetics can prolong peripheral nerve blocks; however, clinical
      safety data are limited, and interscalene blocks have not been studied. The
      present study was designed to test the hypothesis that dexmedetomidine added to
      ropivacaine would safely enhance the duration of analgesia without adverse
      effects when compared with ropivacaine alone. METHODS: We conducted a single
      center, prospective, randomized, triple-blind, controlled trial of 62 patients
      undergoing elective shoulder surgery under general anesthesia with an
      interscalene block. Patients underwent ultrasound-guided interscalene blocks
      using either 12 mL of 0.5% ropivacaine or 0.5% ropivacaine plus 150-ug
      dexmedetomidine. The primary outcomes were self-reported duration of the nerve
      block and safety assessment (adverse effects and neurological sequelae). Data
      were analyzed in a blinded fashion. RESULTS: The median duration of the nerve
      block was 18 hours (95% confidence interval, 18-20) in the dexmedetomidine group
      and 14 hours (95% confidence interval, 14-16) in the ropivacaine group (P =
      0.0001). Dexmedetomidine also lowered pain scores for the first 14 hours
      postoperatively and significantly hastened the time to sensory (P = 0.04) and
      motor (P = 0.002) block onset. Dexmedetomidine lowered heart rate but blood
      pressures were stable. Plasma levels of ropivacaine were not different between
      groups, and plasma dexmedetomidine levels were relatively low. There were no
      adverse events or neurological sequelae. CONCLUSIONS: Dexmedetomidine added to
      ropivacaine for interscalene blocks increased the duration of the nerve block and
      improved postoperative pain. These additional efficacy and safety data should
      encourage further study of peripheral perineural dexmedetomidine in humans.

PMID- 24317235
TI  - [Governance of tertiary referral hospitals in the Democratic Republic of the
      Congo: a critical interpretive synthesis of the literature].
AB  - INTRODUCTION: Because hospitals are complex enterprises requiring adaptive
      systems, it is appropriate to apply the theory and terminology of governance or
      even better adaptive governance to the interpretation of their management. This
      study focused on understanding hospital governance in Logo, Bunia, and Katana,
      three hospitals in two regions of the eastern DRC, which has been characterized
      by intermittent armed conflict since 1996. In such a context of war and
      continuous insecurity, how can governance be interpreted for hospitals required
      to adapt to a constantly changing environment to be able to continue to provide
      health care? METHODOLOGY: A critical interpretive synthesis of the literature,
      identified by searching for keywords related to governance. RESULTS: The concepts
      of governance, adaptive governance, performance, leadership, and complex adaptive
      system concepts are defined. The interpretation of the concepts helps us to
      better understand (1) the hospital as a complex adaptive system, (2) the
      governance of tertiary referral hospitals, (3) analysis of hospital performance,
      and (4) leadership for good governance of these hospitals. DISCUSSION: The
      interpretation of these concepts raises several questions about their application
      to the eastern DRC. Conclusion. This critical interpretive synthesis opens the
      door to a new way of exploring tertiary hospitals and their governance in the
      eastern DRC.

PMID- 24317236
TI  - Bipolar electric cauterization as adjuvant treatment after curettage of
      aneurysmal bone cysts of the hand.
AB  - Almost all aneurysmal bone cysts of the hand were managed with either simple
      curettage plus or minus bone graft or en block excision and autograft
      reconstruction. The high recurrence rate is a major disadvantage of the former
      technique, whereas complexity/donor-site morbidities are known disadvantages of
      the latter technique. In the long bones of the lower limbs, adjuvant therapy
      after curettage is known to reduce the recurrence rate. This article introduces
      adjuvant bipolar electrical cauterization after curettage of aneurysmal bone
      cysts of the hands. This technique was used in 6 cases including 1 case with a
      recurrent lesion after curettage done elsewhere. Complications have been minimal
      and there was no recurrence at a mean follow-up of 3 years. Although the number
      of cases in this series is small, the favorable results warrant trying the
      technique in a multicenter comparative study. 

PMID- 24317237
TI  - Transoral Open Reduction for Subcondylar Fractures of the Mandible Using an
      Angulated Screwdriver System.
AB  - BACKGROUND: The management of subcondylar mandibular fractures has been a matter
      of controversy. Although closed reduction is the most useful method, it can be
      difficult to achieve anatomical reduction with this technique compared with open
      reduction and internal fixation (ORIF). Most surgeons prefer to treat subcondylar
      fractures by extraoral approaches rather than intraoral approaches because
      extraoral approaches provide good visualization of the operative field. The
      retromandibular, submandibular, and perilobular approaches are commonly performed
      in the treatment of displaced condylar or subcondylar fractures and that the
      functional results of these treatments are good. However, extraoral approaches
      have a high rate of surgical complications such as salivary fistula formation,
      visible scarring, and facial nerve injury, compared with intraoral approaches.
      Therefore, this clinical study evaluated the clinical results of ORIF for
      mandibular subcondylar fractures through a transoral approach using an angulated
      screwdriver system without endoscopic assistance. METHODS: A study was conducted
      between March 2011 and October 2012. Eleven patients with subcondylar fractures
      of the mandible were treated through a transoral approach using an angulated
      screwdriver. There were 10 male patients and 1 female patient aged 21 to 72 years
      (mean, 38 years). Nine patients had a symphyseal or parasymphyseal fracture, and
      2 patients had isolated subcondylar fractures of the mandible. RESULTS: Eleven
      patients with subcondylar fractures of the mandible were treated with a transoral
      approach using an angulated screwdriver. The subcondylar fracture was on the left
      side in 6 patients and on the right in 5. All patients achieved satisfactory
      ranges of temporomandibular joint movement with an interincisal distance of more
      than 40 mm without deviation and stable individual centric occlusion. The maximum
      operation duration was 165 minutes, and the average duration of ORIF was 97
      minutes. The association between the operation duration and the number of
      operations was statistically significant. CONCLUSIONS: Our clinical study shows
      that subcondylar fractures of the mandible can be treated using an angulated
      screwdriver system through a transoral approach and that this technique provides
      reliable, satisfactory, and safe clinical outcomes.

PMID- 24317238
TI  - Patient-reported outcomes and satisfaction after total skin-sparing mastectomy
      and immediate expander-implant reconstruction.
AB  - BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the nipple
      areolar complex skin has become more widely accepted. Few studies looking at
      outcomes after TSSM and immediate reconstruction have focused on patient-reported
      outcomes and trends in satisfaction over time. METHODS: Prospective evaluation of
      patients undergoing TSSM and immediate expander-implant reconstruction was
      performed. Patients completed the BREAST-Q questionnaire preoperatively and again
      at 1 month, 6 months, and 1 year postoperatively. Mean scores in each BREAST-Q
      domain were assessed at each time point. Domains were scored on a 0- to 100-point
      scale. RESULTS: Survey completion rate was 55%; BREAST-Q scores were calculated
      from responses from 28 patients. Mean overall satisfaction with breasts declined
      at 1 month (69.8 to 46.1, P<0.001), but then returned to baseline by 1 year. Mean
      scores also declined at 1 month in the psychosocial (75.7-67.4, P=0.2) and sexual
      (58.3-46.7, P=0.06) domains, but returned to baseline by 1 year. Mean nipple
      satisfaction score was 76.4 at 1 year, with 89% of patients reporting
      satisfaction with nipple appearance. Satisfaction with nipple position and
      sensation was lower, with only 56% of patients reporting satisfaction with nipple
      position and 40% with nipple sensation. CONCLUSIONS: After TSSM and immediate
      reconstruction, patient satisfaction with their breasts, as well as psychosocial
      and sexual well-being, returns to baseline by 1 year. Although overall nipple
      satisfaction is high, patients often report dissatisfaction with nipple position
      and sensation; appropriate preoperative counseling is important to set realistic
      expectations.

PMID- 24317240
TI  - The Use of Frozen Section in the Excision of Cutaneous Malignancy: A Queensland
      Experience.

PMID- 24317239
TI  - Outcomes Analysis of Biologic Mesh Use for Abdominal Wall Reconstruction in Clean
      Contaminated and Contaminated Ventral Hernia Repair.
AB  - BACKGROUND: Repair of grade 3 and grade 4 ventral hernias is a distinct
      challenge, given the potential for infection, and the comorbid nature of the
      patient population. This study evaluates our institutional outcomes when
      performing single-stage repair of these hernias, with biologic mesh for abdominal
      wall reinforcement. METHODS: A prospectively maintained database was reviewed for
      all patients undergoing repair of grade 3 (potentially contaminated) or grade 4
      (infected) hernias, as classified by the Ventral Hernia Working Group. All those
      patients undergoing repair with component separation techniques and biologic mesh
      reinforcement were included. Patient demographics, comorbidities, and
      postoperative complications were analyzed. Univariate analysis was performed to
      define factors predictive of hernia recurrence and wound complications. RESULTS:
      A total of 41 patients underwent single-stage repair of grade 3 and grade 4
      hernias during a 4-year period. The overall postoperative wound infection rate
      was 15%, and hernia recurrence rate was 12%. Almost all recurrences were seen in
      grade 4 hernia repairs, and in those patients undergoing bridging repair of the
      hernia. One patient required removal of the biologic mesh. Those factors
      predicting hernia recurrence were smoking (P = 0.023), increasing body mass index
      (P = 0.012), increasing defect size (P = 0.010), and bridging repair (P = 0.042).
      No mesh was removed due to perioperative infection. Mean follow-up time for this
      patient population was 25 months. CONCLUSIONS: Single-stage repair of grade 3
      hernias performed with component separation and biologic mesh reinforcement is
      effective and offers a low recurrence rate. Furthermore, the use of biologic mesh
      allows for avoidance of mesh explantation in instances of wound breakdown or
      infection. Bridging repairs are associated with a high recurrence rate, as is
      single-stage repair of grade 4 hernias.

PMID- 24317241
TI  - Hydrogen sulfide mitigates reperfusion injury in a porcine model of vascularized
      composite autotransplantation.
AB  - BACKGROUND: Devastating extremity injuries are prevalent but often survivable on
      the modern battlefield. These complex injuries require advanced methods of
      reconstruction, involving prolonged ischemic periods and reperfusion injury.
      Using our group's validated porcine model of gracilis myocutaneous flap
      transplantation, this study demonstrates that an interim perfusion of hydrogen
      sulfide (H2S) mitigates the effects of reperfusion injury in the setting of
      delayed restoration of blood flow. METHODS: A gracilis myocutaneous flap (200-400
      g; surface area, 250 cm2) was procured from the hind limb of a Yorkshire swine
      (70-90 kg, n=16). The right external carotid artery and the internal jugular vein
      are the recipient axis. Group 1 (control, n = 6) underwent delayed anastomosis
      with a 3-hour ischemic period. Group 2 (n=10) underwent a similar delayed
      anastomosis with an interim perfusion of H2S during the ischemic period. The
      animals survived for 14 days. Systemic biomarker assays for skeletal muscle
      tissue injury (creatine kinase, lactate dehydrogenase, and aspartate
      transaminase) and proinflammatory markers (tumor necrosis factor alpha and
      interleukin 6) provide assessment of reperfusion injury at the cellular level.
      RESULTS: The control animals (3 hours of ischemia with an interim perfusion of
      heparinized saline) demonstrated increased levels of injury biomarkers and
      proinflammatory cytokines compared with the animals receiving H2S infusion and
      identical ischemic interval. The control flaps had a mean creatine kinase level
      of 2803*10 U/L (+/-80*103), compared with the H2S group, which had a mean of
      99*103 U/L (+/-14*103; P=0.0007 at postoperative day 2). lactate dehydrogenase
      levels (mean) were 26*103 U/L (+/-8*103) versus 9*103 U/L (+/-3*103; P=0.0004)
      and aspartate transaminase levels (mean) were 1651 U/L (+/-324) versus (873 U/L
      [+/-279]; P=0.0013) for the control and treatment groups, respectively.
      Similarly, an intergroup difference in IL-6 was found, although not statistically
      significant. Tumor necrosis factor alpha levels (mean) were 93 pg/mL (+/-14)
      versus 39 pg/mL (+/-4; P=0.0013) for the control and treatment groups,
      respectively. CONCLUSIONS: This study demonstrated the mitigating properties of
      H2S on reperfusion injury. Interim perfusion with H2S resulted in diminution of
      ischemia-dependent biomarkers after 3 hours of ischemia. Follow-up studies will
      translate these findings as an evolving method for reconstructing previously
      unreconstructable injuries.

PMID- 24317242
TI  - Increasing value in plagiocephaly care: a time-driven activity-based costing
      pilot study.
AB  - BACKGROUND: Process management within a health care setting is poorly understood
      and often leads to an incomplete understanding of the true costs of patient care.
      Using time-driven activity-based costing methods, we evaluated the high-volume,
      low-complexity diagnosis of plagiocephaly to increase value within our clinic.
      METHODS: A total of 59 plagiocephaly patients were evaluated in phase 1 (n = 31)
      and phase 2 (n = 28) of this study. During phase 1, a process map was created,
      encompassing each of the 5 clinicians and administrative personnel delivering 23
      unique activities. After analysis of the phase 1 process maps, average times as
      well as costs of these activities were evaluated for potential modifications in
      workflow. These modifications were implemented in phase 2 to determine overall
      impact on visit-time and costs of care. RESULTS: Improvements in patient
      education, workflow coordination, and examination room allocation were
      implemented during phase 2, resulting in a reduced patient visit-time of 13:25
      (19.9% improvement) and an increased cost of $8.22 per patient (7.7% increase)
      due to changes in physician process times. However, this increased cost was
      directly offset by the availability of 2 additional appointments per day,
      potentially generating $7904 of additional annual revenue. Quantifying the impact
      of a 19.9% reduction in patient visit-time at an increased cost of 7.7% resulted
      in an increased value ratio of 1.113. CONCLUSIONS: This pilot study effectively
      demonstrates the novel use of time-driven activity-based costing in combination
      with the value equation as a metric for continuous process improvement programs
      within the health care setting.

PMID- 24317243
TI  - An experimental comparison of the effects of propolis, curcumin, and
      methylprednisolone on crush injuries of the sciatic nerve.
AB  - BACKGROUND: Propolis and curcumin have antioxidant, anti-inflammatory,
      immunomodulatory, and neuroprotective features. The goal of this study was to
      determine the effects of propolis and curcumin on nerve healing in rat sciatic
      nerve crush injuries and to compare these effects with results obtained using
      steroid treatment. METHODS: In the sham group, the right sciatic nerves of rats
      were dissected and exposed, and the skin was closed without any additional
      manipulation. In the control group (group C), after the right sciatic nerves of
      rats were exposed, crush damage was inflicted using a surgical clamp. In the
      control-methylprednisolone group, crush injuries were inflicted on sciatic nerves
      as in group C. After injury, 1-mg/kg methylprednisolone was administered daily
      for 6 days and was then tapered for 4 days. In the curcumin group, crush injuries
      were inflicted on sciatic nerves as in group C. Then, 100-mg/kg curcumin was
      given every day. In the propolis group, crush injuries were inflicted on sciatic
      nerves as in group C. Then, 200-mg/kg propolis was given every day. Rats were
      evaluated after 28 days using functional (walking track analysis and
      electrophysiological measurements), histomorphometric, electron microscopic, and
      muscle weight measurements. RESULTS: Compared to the control groups, the curcumin
      and propolis groups had better functional (walking track analysis and
      electrophysiological) results after experimental peripheral nerve crush injury.
      CONCLUSIONS: Curcumin and propolis, 2 traditional drugs, had a positive effect on
      nerve crush injuries. We are convinced that they can be used to support routine
      treatment in such nerve injuries.

PMID- 24317244
TI  - Predictive risk factors of venous thromboembolism in autologous breast
      reconstruction surgery.
AB  - BACKGROUND: Venous thromboembolism (VTE) can be a significant cause of morbidity
      and mortality in autologous breast reconstruction surgery. The aim of this study
      was to evaluate the effect of patient characteristics, comorbidities, payer type,
      reconstruction type, reconstruction timing, radiation, chemotherapy, and teaching
      status of hospital on VTE (deep venous thrombosis and/or pulmonary embolism) in
      autologous breast reconstructive surgery. METHODS: Using the Nationwide Inpatient
      Sample (NIS) database, we examined the clinical data of patients who underwent
      autologous breast reconstructive surgery in 2009 to 2010 in the United States.
      Univariate and multivariate regression analyses were performed to identify
      factors predictive of in-hospital VTE. RESULTS: A total of 35,883 patients
      underwent autologous breast reconstructive surgery during this period. Overall
      rate of VTE was 0.13%. The highest rate of VTE (0.26%) was observed in pedicled
      transverse rectus abdominis myocutaneous flap. Patients who experienced VTE had
      significantly longer mean hospital stay (11.6 vs 3.9 days; P < 0.001) and higher
      mean total hospital charges ($146,432 vs $61,794; P < 0.001) compared with non
      VTE patients; however, there was no significant difference observed in mortality
      rate (VTE, 0.0% vs non-VTE, 0.04%; P = 0.886). Using multivariate regression
      analysis, immediate reconstruction after mastectomy (adjusted odds ratio [AOR],
      5.4), older than 65 years (AOR, 4.2), obesity (AOR, 3.7), history of chemotherapy
      (AOR, 3.5), and chronic lung disease (AOR, 2.5) were associated with higher risk
      of VTE. There was no association between race, payer type, diabetes,
      hypertension, liver disease, congestive heart failure, peripheral vascular
      disease, chronic kidney disease, smoking, reconstruction type, radiation, or
      teaching status of hospital on VTE. CONCLUSIONS: In patients undergoing
      autologous breast reconstruction surgery, immediate reconstruction, older than 65
      years, obesity, history of chemotherapy, and chronic lung disease are all
      independent predictors of higher VTE. Surgeons should consider these factors and
      use appropriate prophylaxis to minimize the risk of VTE development.

PMID- 24317245
TI  - Effective wound healing in streptozotocin-induced diabetic rats by adipose
      derived stromal cell transplantation in plasma-gel containing fragmin/protamine
      microparticles.
AB  - We investigated the effectiveness of the application of inbred adipose-derived
      stromal cells (IR-ASCs) in high inbred rat plasma (IRP) (6%)-Dulbecco modified
      Eagle medium (DMEM) gel with fragmin/protamine microparticles (F/P MPs) (IR-ASCs
      + IRP-DMEM gel + F/P MPs) on wound healing in streptozotocin-induced diabetic
      rats. F/P MPs have previously been used as a cell carrier for IR-ASCs in inbred
      Fisher 344 rats and for preservation and controlled release of various cytokines
      in IRP-DMEM gel. We applied IR-ASCs + IRP-DMEM gel + F/P MPs to full-thickness
      skin excisions on the backs of the diabetic rats. The statistical significance of
      wound closure was evaluated on postwounding days 3, 7, 10, and 14, and the skin
      area surrounding the wound was removed for histological examination on days 7 and
      14. The wound closure rate and histological examination of wounds treated with IR
      ASCs + IRP-DMEM gel + F/P MPs demonstrated significantly advanced
      epithelialization, capillary formation, and granulation tissue formation. When
      DiI-labeled IR-ASCs + IRP-DMEM gel + F/P MPs were applied to full-thickness skin
      wounds on the backs of the diabetic rats, histological observation at 2 weeks
      showed appearances of both DiI-labeled granulation tissue and CD31-immunostained
      microvessels in the transplant areas. A portion of the transplanted IR-ASCs + IRP
      DMEM gel + F/P MPs had been taken up into the granulation tissues to promote
      wound healing. Thus, IR-ASCs + IRP-DMEM gel + F/P MPs were effective for
      repairing healing-impaired wounds such as those arising in the diabetic rats. 

PMID- 24317246
TI  - Gait cycle analysis: parameters sensitive for functional evaluation of peripheral
      nerve recovery in rat hind limbs.
AB  - BACKGROUND: Video-assisted gait kinetics analysis has been a sensitive method to
      assess rat sciatic nerve function after injury and repair. However, in conduit
      repair of sciatic nerve defects, previously reported kinematic measurements
      failed to be a sensitive indicator because of the inferior recovery and
      inevitable joint contracture. OBJECTIVE: This study aimed to explore the role of
      physiotherapy in mitigating joint contracture and to seek motion analysis indices
      that can sensitively reflect motor function. METHODS: Data were collected from 26
      rats that underwent sciatic nerve transection and conduit repair. Regular
      postoperative physiotherapy was applied. Parameters regarding step length, phase
      duration, and ankle angle were acquired and analyzed from video recording of gait
      kinetics preoperatively and at regular postoperative intervals. RESULTS: Stride
      length ratio (step length of uninjured foot/step length of injured foot), percent
      swing of the normal paw (percentage of the total stride duration when the
      uninjured paw is in the air), propulsion angle (toe-off angle subtracted by
      midstance angle), and clearance angle (ankle angle change from toe off to
      midswing) decreased postoperatively comparing with baseline values. The gradual
      recovery of these measurements had a strong correlation with the post-nerve
      repair time course. CONCLUSIONS: Ankle joint contracture persisted despite
      rigorous physiotherapy. Parameters acquired from a 2-dimensional motion analysis
      system, that is, stride length ratio, percent swing of the normal paw, propulsion
      angle, and clearance angle, could sensitively reflect nerve function impairment
      and recovery in the rat sciatic nerve conduit repair model despite the existence
      of joint contractures.

PMID- 24317247
TI  - Patient-centered wound teleconsultation for cutaneous wounds: a feasibility
      study.
AB  - INTRODUCTION: The purpose of this study was to investigate the feasibility of
      patient-centered teleconsultation for various cutaneous wounds by using store-and
      forward technology. MATERIALS AND METHODS: From July 2011 to November 2011, 53
      patients with various wound conditions were enrolled in this study. The patients
      took their own wound images shortly before face-to-face consultations with a
      plastic surgeon, and the images were sent via e-mail to another 3 remote plastic
      surgeons along with brief medical information. All 4 surgeons completed a
      standard questionnaire individually, which addressed questions regarding the
      presence of wound conditions (gangrene, necrosis, erythema, and
      cellulitis/infection), as well as suggested clinical treatment with antibiotics
      and debridement. The evaluations were compared among the 3 remote surgeons as
      well as the remote and onsite surgeons. RESULTS: The 53 wounds included in our
      study exhibited different causative mechanisms and locations on the body. The
      concordances between the remote and onsite surgeons were 92%, 79%, 83%, and 85%
      regarding the presence of gangrene, necrosis, erythema, and cellulitis/infection,
      respectively. The agreement rates regarding the treatment suggestion with
      antibiotic use and debridement between the remote surgeons and the onsite surgeon
      were both 83%. The remote surgeons reported high specificity, at least 84%, in
      all parameters of wound descriptions or treatment suggestions. CONCLUSIONS: The
      patient-centered teleconsultation system based on store-and-forward technology is
      a feasible tool for wound management, and it shows promises in future clinical
      applications by decreasing clinic visits.

PMID- 24317248
TI  - The Use of a Superiorly Based Melolabial Interpolated Flap for Reconstruction of
      Anterior Oronasal Fistulas: An Easy and Practical Solution.
AB  - PURPOSE: This study aimed to propose the use of a superiorly based melolabial
      interpolated flap for reconstruction of anteriorly located oronasal fistulas
      maxillary defects. MATERIALS AND METHODS: Using a prospective study design, we
      evaluated indications and outcomes of the reconstructive technique using the
      interpolated melolabial flap in 6 patients affected by anteriorly located
      maxillary defects with naso-sinonasal communication. The cases differed in
      demographic characteristics and etiology of the defect. The outcome variables
      were flap vitality/failure and persistent/recurrent oronasal fistula. Both the
      outcomes were clinically evaluated. RESULTS: No partial or total flap failures
      were recorded. Two patients experienced recurrent oronasal fistula after previous
      attempts of correction that required second surgery repair; in both cases, the
      melolabial flap was available and functional for the secondary procedure.
      CONCLUSIONS: In selected cases, the superiorly based interpolated melolabial flap
      could represent a valuable choice for repairing of anteriorly located maxillary
      defects with oronasal fistulas.

PMID- 24317249
TI  - Versatility of the reversed superficial peroneal neurocutaneous island flap in
      the coverage of ankle and foot.
AB  - BACKGROUND: In the last decades, the skin island flap supplied by the vascular
      axis of sensitive superficial nerves, like the sural and saphenous nerves, has
      emerged as one of the most ideal reconstructive options for soft tissue coverage
      of lower limbs. The nutrient vessels of reversed superficial peroneal
      neurocutaneous island flap have been well described; however, it is still not
      commonly clinically applied. The aim of this study was to evaluate the efficacy
      of reversed superficial peroneal neurocutaneous island flap for coverage of ankle
      and foot. STUDY DESIGN: This is a retrospective and descriptive study of reversed
      superficial peroneal neurocutaneous island flap which was carried out for
      reconstruction of ankle and foot. PLACE AND DURATION OF STUDY: This study was
      conducted at the Department of Repair and Reconstructive Surgery, the 6th
      People's Hospital affiliated to Shanghai Jiaotong University, during a period of
      51 months from July 2008 to October 2012. PATIENTS AND METHODS: A total of 12
      patients with soft tissue defect of ankle and foot were included in the series;
      reversed superficial peroneal neurocutaneous island flap was performed on each
      case if relevant indications permitted. Preoperative and postoperative data of
      each patient, including etiology, size of defect, dimension of flap,
      complications, and functional and aesthetic results were noted. RESULTS: Among
      the 12 patients, there were 8 men and 4 women with an average age of 40.7 years
      (22-65 years) and with a mean follow-up time of 17.3 months (10-23 months). Most
      patients (11 patients) were posttraumatic. The size of the flap ranged from 48 to
      108 cm2. Postoperatively, 11 flaps survived uneventfully, whereas marginal venous
      congestion was seen in the remaining patient, and secondary healing was achieved
      by conservative treatment. CONCLUSIONS: The reversed superficial peroneal
      neurocutaneous island flap could be an excellent alternative to other
      neurocutaneous perforator flap in the soft tissue reconstruction of foot and
      ankle.

PMID- 24317250
TI  - Professional burnout among US plastic surgeons: results of a national survey.
AB  - PURPOSE: Little is known about professional burnout among plastic surgeons. Our
      purpose is to describe its prevalence among a large national sample of plastic
      surgeons and identify contributing factors. METHODS: A mailed, self-administered
      survey was sent to 708 plastic surgeons who were randomly sampled from the
      American Society of Plastic Surgeons national membership (71% response rate). The
      dependent variable was professional burnout, measured by 3 subscales from the
      validated Maslach Burnout Inventory-Human Services Survey. "High" scores in
      either the emotional exhaustion or depersonalization subscale categories predict
      professional burnout. The independent variables included surgeon sociodemographic
      and professional characteristics. chi was used for the bivariate analyses.
      RESULTS: Nearly one third (29%) of surgeons scored high in subscale categories
      predictive of professional burnout. Factors associated with high emotional
      exhaustion scores included surgeon age, 40-50 years (P = 0.03); fair/poor
      physician health (P < 0.01); ER call (P < 0.01); >60 work hours per week (P =
      0.03); primarily reconstructive practice (P < 0.01); private practice (P = 0.01);
      and group practice (P = 0.02). Factors associated with high depersonalization
      scores included fair/poor physician health (P= 0.01); ER call (P < 0.01); private
      practice (P = 0.01); and group practice (P = 0.02). CONCLUSIONS: Nearly one third
      of plastic surgeons have signs of professional burnout. Middle-aged surgeons and
      those in poor health are most at risk; along with those who have a reconstructive
      rather than cosmetic practice, long work hours, ER call responsibility, a
      nonacademic setting. and group as compared to solo practice. These data have
      important implications for future workforce shortages and health care quality.

PMID- 24317251
TI  - A Simple Technique to Create Cheek Dimples.
AB  - BACKGROUND: Cheek dimple is a commonly requested aesthetic procedure, especially
      in the Arabian Gulf area. AIM: This work describes the authors' experience in
      creation of cheek dimples using simple rapid technique. PATIENTS AND METHODS:
      This study included 116 dimples in 74 patients. The dimple is done through an
      intraoral stab incision and prolene suture to fix the dermis of the cheek skin to
      the underlying buccinator muscle. RESULTS: Eighty-six percent of patients had
      satisfactory results. The most common complications were fading or complete
      disappearance of the dimple in 14 dimples and infection in 5 patients.
      CONCLUSIONS: This technique is very simple, very rapid, easy to execute, and
      gives satisfactory results in up to 86% of patients. This article also highlights
      the important information that must be discussed with the patients
      preoperatively.

PMID- 24317252
TI  - Refined DNase-seq protocol and data analysis reveals intrinsic bias in
      transcription factor footprint identification.
AB  - Sequencing of DNase I hypersensitive sites (DNase-seq) is a powerful technique
      for identifying cis-regulatory elements across the genome. We studied the key
      experimental parameters to optimize performance of DNase-seq. Sequencing short
      fragments of 50-100 base pairs (bp) that accumulate in long internucleosome
      linker regions was more efficient for identifying transcription factor binding
      sites compared to sequencing longer fragments. We also assessed the potential of
      DNase-seq to predict transcription factor occupancy via generation of nucleotide
      resolution transcription factor footprints. In modeling the sequence-specific
      DNase I cutting bias, we found a strong effect that varied over more than two
      orders of magnitude. This indicates that the nucleotide-resolution cleavage
      patterns at many transcription factor binding sites are derived from intrinsic
      DNase I cleavage bias rather than from specific protein-DNA interactions. In
      contrast, quantitative comparison of DNase I hypersensitivity between states can
      predict transcription factor occupancy associated with particular biological
      perturbations. 

PMID- 24317253
TI  - Demonstrating the feasibility of large-scale development of standardized assays
      to quantify human proteins.
AB  - Multiple reaction monitoring (MRM) mass spectrometry has been successfully
      applied to monitor targeted proteins in biological specimens, raising the
      possibility that assays could be configured to measure all human proteins. We
      report the results of a pilot study designed to test the feasibility of a large
      scale, international effort for MRM assay generation. We have configured,
      validated across three laboratories and made publicly available as a resource to
      the community 645 novel MRM assays representing 319 proteins expressed in human
      breast cancer. Assays were multiplexed in groups of >150 peptides and deployed to
      quantify endogenous analytes in a panel of breast cancer-related cell lines. The
      median assay precision was 5.4%, with high interlaboratory correlation (R(2) >
      0.96). Peptide measurements in breast cancer cell lines were able to discriminate
      among molecular subtypes and identify genome-driven changes in the cancer
      proteome. These results establish the feasibility of a large-scale effort to
      develop an MRM assay resource. 

PMID- 24317255
TI  - Best combination of promoter and micellar catalyst for the rapid conversion of
      sorbitol to glucose.
AB  - Kinetic data for oxidation of D-sorbitol to glucose by hexavalent chromium in
      aqueous medium and aqueous surfactant medium (SDS, TX-100) have been reported.
      Effect of promoter such as PA, bipy and phenanthroline on the reaction has been
      investigated. The reaction is performed under pseudo first order condition with
      an excess of substrate over the oxidant. The reaction is first order with respect
      to substrate and oxidant. The micelles have a catalytic effect on the reaction.
      Combination of phen and TX-100 produces almost twelve times increase in rate of
      oxidation. 

PMID- 24317254
TI  - Quantifying cell-generated mechanical forces within living embryonic tissues.
AB  - Cell-generated mechanical forces play a critical role during tissue morphogenesis
      and organ formation in the embryo. Little is known about how these forces shape
      embryonic organs, mainly because it has not been possible to measure cellular
      forces within developing three-dimensional (3D) tissues in vivo. We present a
      method to quantify cell-generated mechanical stresses exerted locally within
      living embryonic tissues, using fluorescent, cell-sized oil microdroplets with
      defined mechanical properties and coated with adhesion receptor ligands. After a
      droplet is introduced between cells in a tissue, local stresses are determined
      from droplet shape deformations, measured using fluorescence microscopy and
      computerized image analysis. Using this method, we quantified the anisotropic
      stresses generated by mammary epithelial cells cultured within 3D aggregates, and
      we confirmed that these stresses (3.4 nN MUm(-2)) are dependent on myosin II
      activity and are more than twofold larger than stresses generated by cells of
      embryonic tooth mesenchyme, either within cultured aggregates or in developing
      whole mouse mandibles. 

PMID- 24317256
TI  - Low temperature synthesis of pure cubic ZrO2 nanopowder: structural and
      luminescence studies.
AB  - Pure cubic zirconia (ZrO2) nanopowder is prepared for the first time by simple
      low temperature solution combustion method without calcination. The product is
      characterized by Powder X-ray Diffraction (PXRD), Scanning Electron Microscopy
      (SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infra Red
      spectroscopy (FTIR) and Ultraviolet-Visible spectroscopy (UV-Vis). The PXRD
      showed the formation of pure stable cubic ZrO2 nanopowders with average
      crystallite size ranging from 6 to 12 nm. The lattice parameters were calculated
      from Rietveld refinement method. SEM micrograph shows fluffy, mesoporous,
      agglomerated particles with large number of voids. TEM micrograph shows honey
      comb like arrangement of particles with particle size ~10 nm. The PL emission
      spectrum excited at 210 nm and 240 nm consists of intense bands centered at ~365
      and ~390 nm. Both the samples show shoulder peak at ~420 nm, along with four weak
      emission bands at ~484, ~528, ~614 and ~726 nm. TL studies were carried out pre
      irradiating samples with gamma-rays ranging from 1 to 5 KGy at room temperature.
      A well resolved glow peak at 377  degrees C is recorded which can be ascribed to
      deep traps. With increase in gamma radiation there is linear increase in TL
      intensity which shows the possible use of ZrO2 as dosimetric material.

PMID- 24317257
TI  - Simultaneous multicomponent spectrophotometric monitoring of methyl and propyl
      parabens using multivariate statistical methods after their preconcentration by
      robust ionic liquid-based dispersive liquid-liquid microextraction.
AB  - A powerful and efficient signal-preprocessing technique that combines local and
      multiscale properties of the wavelet prism with the global filtering capability
      of orthogonal signal correction (OSC) is applied for pretreatment of
      spectroscopic data of parabens as model compounds after their preconcentration by
      robust ionic liquid-based dispersive liquid-liquid microextraction method (IL
      DLLME). In the proposed technique, a mixture of a water-immiscible ionic liquid
      (as extraction solvent) [Hmim][PF6] and disperser solvent is injected into an
      aqueous sample solution containing one of the IL's ions, NaPF6, as extraction
      solvent and common ion source. After preconcentration, the absorbance of the
      extracted compounds was measured in the wavelength range of 200-700 nm. The
      wavelet orthogonal signal correction with partial least squares (WOSC-PLS) method
      was then applied for simultaneous determination of each individual compound.
      Effective parameters, such as amount of IL, volume of the disperser solvent and
      amount of NaPF6, were inspected by central composite design to identify the most
      important parameters and their interactions. The effect of pH on the sensitivity
      and selectivity was studied according to the net analyte signal (NAS) for each
      component. Under optimum conditions, enrichment factors of the studied compounds
      were 75 for methyl paraben (MP) and 71 for propyl paraben (PP). Limits of
      detection for MP and PP were 4.2 and 4.8 ng mL(-)(1), respectively. The root mean
      square errors of prediction for MP and PP were 0.1046 and 0.1275 MUg mL(-)(1),
      respectively. The practical applicability of the developed method was examined
      using hygienic, cosmetic, pharmaceutical and natural water samples.

PMID- 24317258
TI  - Bulk growth of ninhydrin single crystals by solvent evaporation method and its
      characterization for SHG and THG applications.
AB  - Ninhydrin is a well-known compound generally used in amino acid synthesis and
      also for detecting the latent fingerprints on porous surfaces. Single crystals
      can be grown by dissolving the compound in double distilled water at ambient
      temperature, and can be used as a potential material for second and third
      harmonic generation applications. The grown specimen was subjected to different
      characterization techniques in order to find out its suitability for device
      fabrication. Its lattice dimensions have been confirmed by X-ray powder
      diffraction and its crystalline quality has been assessed by high resolution X
      ray diffraction and X-ray topography methods. The presence of functional groups
      was identified from HETCOR analysis and confirmed the absence of impurities
      during crystallization. Its optical properties have been examined by
      photoluminescence and birefringence analyses. Its thermal parameters such as
      thermal diffusivity, thermal conductivity and specific capacity have been carried
      out by following photopyroelectric method. Third order nonlinear optical
      measurements have been carried out using Z-scan technique and its nonlinear
      optical absorption coefficient has been determined. 

PMID- 24317259
TI  - Cyclodextrin polymer/Fe3O4 nanocomposites as solid phase extraction material
      coupled with UV-vis spectrometry for the analysis of rutin.
AB  - In this paper, carboxymethyl-hydroxypropyl-beta-cyclodextrin polymer modified
      magnetic particles Fe3O4 (CM-HP-beta-CDCP-MNPs) were prepared and applied to
      magnetic solid phase extraction of rutin combined with UV-visible spectrometry
      detection. The synthesized magnetic particles were characterized by element
      analysis, Fourier transform infrared spectra, thermal gravimetric analysis, and
      transmission electron microscopy. Several variables affecting the extraction and
      desorption of rutin such as pH, the amount of adsorbent, the type and volume of
      eluent, extraction and desorption time, and temperature were investigated. The
      maximum adsorption capacity was 67.0 mg g(-1) for rutin with the equilibrium time
      of 30 min at room temperature, and the adsorbent could be reused for 10 times. A
      calibration curve was linear in the range of 0.05-8.00 MUg mL(-1) with a relative
      standard deviation of 2.9% (n=5, c=4.0 MUg mL(-1)). The limit of detection was
      7.0 ng mL(-1). The interaction mechanism between the adsorbent and rutin was also
      studied. Feasibility of this method was validated by the analysis of rutin
      tablets and lotus plumule.

PMID- 24317260
TI  - Hydrogen bond strengthening of cis-trans glyoxal dimers in electronic excited
      states: a theoretical study.
AB  - The second-order approximate coupled-cluster (CC2) method was performed to
      investigate the excited state hydrogen-bonding properties of Glyoxal (C2H2O2, Gl)
      dimers. Since the strengthening and weakening of hydrogen bonds can be
      investigated by monitoring the vibrational absorption spectra of some hydrogen
      bonded groups in different electronic states, the infrared spectra of the
      hydrogen-bonded Gl-Gl complexes in both of the ground state and the S1
      electronically excited state are calculated using the MP2/CC2 methods
      respectively. We demonstrated that the intermolecular hydrogen bond C=O?H-C
      between two glyoxal molecules is significantly strengthened in the electronically
      excited S1 state upon photoexcitation of the hydrogen-bonded Gl-Gl complexes.

PMID- 24317261
TI  - A yellow-emitting phosphor of Mn(2+)-doped Na2CaP2O7.
AB  - A yellow-emitting Na2CaP2O7:Mn(2+)phosphors have been synthesized by solid state
      reaction. The crystal structure, photoluminescence properties as well as
      concentration quenching mechanism have been investigated. The (4)T1-(6)A1
      emission of Mn(2+)in Na2CaP2O7 phosphor ranges from 500 to 650 nm and exhibits a
      red shift while increasing the Mn(2+)concentration. The crystal field strength is
      calculated based on the combination of excitation spectrum and Tanabe-Sugano
      diagram. The chromaticity coordinates of Na2CaP2O7:Eu(2+), Mn(2+)phosphors were
      discussed in order to develop the potential application in white light-emitting
      diodes (LEDs).

PMID- 24317262
TI  - Structural, optical, electron paramagnetic, thermal and dielectric
      characterization of chalcopyrite.
AB  - Chalcopyrite (CuFeS2) a variety of pyrite minerals was investigated through
      spectroscopic techniques and thermal analysis. The morphology and elemental
      analysis of the chalcopyrite have been done by high resolution SEM with EDAX. The
      lattice parameters were from the powder diffraction data (a=5.3003+/-0.0089 A,
      c=10.3679+/-0.0289 A; the volume of the unit cell=291.266 A(3) with space group
      I42d (122)). The thermal decomposition behavior of chalcopyrite was studied by
      means of thermogravimetric analysis at three different heating rates 10, 15 and
      20  degrees C/min. The values of effective activation energy (Ea), pre
      exponential factor (ln A) for thermal decomposition have been measured at three
      different heating rates by employing Kissinger, Kim-Park and Flynn-Wall methods.
      Dielectric studies at different temperatures have also been carried out and it
      was found that both dielectric constant and dielectric loss decreases with the
      increase of frequency.

PMID- 24317263
TI  - Synthesis of mononuclear copper(II) complexes of acyclic Schiff's base ligands:
      spectral, structural, electrochemical, antibacterial, DNA binding and cleavage
      activity.
AB  - The mononuclear copper(II) complexes (1&2) of ligands L(1) [N,N'-bis(2-hydroxy-5
      methylbenzyl)-1,4-bis(3-iminopropyl)piperazine] or L(2) [N,N'-bis(2-hydroxy-5
      bromobenzyl)-1,4-bis(3-iminopropyl) piperazine] have been synthesized and
      characterised. The single crystal X-ray study had shown that ligands L(1) and
      L(2) crystallize in a monoclinic crystal system with P21/c space group. The
      mononuclear copper(II) complexes show one quasireversible cyclic voltammetric
      response near cathodic region (-0.77 to -0.85 V) in DMF assignable to the
      Cu(II)/Cu(I) couple. Binding interaction of the complexes with calf thymus DNA
      (CT DNA) investigated by absorption studies and fluorescence spectral studies
      show good binding affinity to CT DNA, which imply both the copper(II) complexes
      can strongly interact with DNA efficiently. The copper(II) complexes showed
      efficient oxidative cleavage of plasmid pBR322 DNA in the presence of 3
      mercaptopropionic acid as reducing agent through a mechanistic pathway involving
      formation of singlet oxygen as the reactive species. The Schiff bases and their
      Cu(II) complexes have been screened for antibacterial activities which indicates
      that the complexes exhibited higher antimicrobial activity than the free ligands.

PMID- 24317264
TI  - Molecular conformational analysis, vibrational spectra and normal coordinate
      analysis of trans-1,2-bis(3,5-dimethoxy phenyl)-ethene based on density
      functional theory calculations.
AB  - The conformational behavior and structural stability of trans-1,2-bis(3,5
      dimethoxy phenyl)-ethene (TDBE) were investigated by using density functional
      theory (DFT) method with the B3LYP/6-311++G(d,p) basis set combination. The
      vibrational wavenumbers of TDBE were computed at DFT level and complete
      vibrational assignments were made on the basis of normal coordinate analysis
      calculations (NCA). The DFT force field transformed to natural internal
      coordinates was corrected by a well-established set of scale factors that were
      found to be transferable to the title compound. The infrared and Raman spectra
      were also predicted from the calculated intensities. The observed Fourier
      transform infrared (FTIR) and Fourier transform (FT) Raman vibrational
      wavenumbers were analyzed and compared with the theoretically predicted
      vibrational spectra. Comparison of the simulated spectra with the experimental
      spectra provides important information about the ability of the computational
      method to describe the vibrational modes. Information about the size, shape,
      charge density distribution and site of chemical reactivity of the molecules has
      been obtained by mapping electron density isosurface with electrostatic potential
      surfaces (ESP). 

PMID- 24317265
TI  - Structural versatility and luminescent properties in d(10) metal ion polymers
      with 1,4-naphthalenedicarboxylate acid and 4,4'-dipyridyl N,N'-dioxide.
AB  - Hydrothermal reactions of d(10) metal ions (Cd(2+) and Zn(2+)) with 1,4
      naphthalenedicarboxylate acid (1,4-H2NDC) and 4,4'-dipyridyl N,N'-dioxide (4,4'
      dpdo) form two three-dimensional grid-like coordination polymers [Cd2(1,4
      NDC)2(4,4'-dpdo)].H2O 1 and [Zn4(MU3-OH)2(1,4-NDC)3(H2O)2](4,4'-dpdo).2H2O 2.
      Both coordination polymers were characterized by single crystal X-ray
      diffraction, IR spectroscopy, XRPD, thermogravimetric and elemental analyses.
      Polymer 1 exhibits rare alternating arranged 1,4-NDC(2)(-) and 4,4'-dpdo spacers
      between adjacent 1D zigzag chains containing Cd-octahedral coordination
      geometries. Polymer 2 is constructed from infrequent chair-like [Zn4(MU3
      OH)2](6+) inorganic SBUs with four- and six-coordination geometries and only 1,4
      NDC(2)(-) as "single-bridge" and "double-bridges" to form a 3D framework. Both
      polymers give strong luminescent emissions in the solid state at room
      temperature. 

PMID- 24317266
TI  - A study of the phosphate mineral kapundaite NaCa(Fe3+)4(PO4)4(OH)3?5(H2O) using
      SEM/EDX and vibrational spectroscopic methods.
AB  - Vibrational spectroscopy enables subtle details of the molecular structure of
      kapundaite to be determined. Single crystals of a pure phase from a Brazilian
      pegmatite were used. Kapundaite is the Fe(3+) member of the wardite group. The
      infrared and Raman spectroscopy were applied to compare the structure of
      kapundaite with wardite. The Raman spectrum of kapundaite in the 800-1400 cm(-1)
      spectral range shows two intense bands at 1089 and 1114 cm(-1) assigned to the
      nu1PO4(3-) symmetric stretching vibrations. The observation of two bands provides
      evidence for the non-equivalence of the phosphate units in the kapundaite
      structure. The infrared spectrum of kapundaite in the 500-1300 cm(-1) shows much
      greater complexity than the Raman spectrum. Strong infrared bands are found at
      966, 1003 and 1036 cm(-1) and are attributed to the nu1PO4(3-) symmetric
      stretching mode and nu3PO4(3-) antisymmetric stretching mode. Raman bands in the
      nu4 out of plane bending modes of the PO4(3-) unit support the concept of non
      equivalent phosphate units in the kapundaite structure. In the 2600-3800 cm(-1)
      spectral range, Raman bands for kapundaite are found at 2905, 3151, 3311, 3449
      and 3530 cm(-1). These bands are broad and are assigned to OH stretching
      vibrations. Broad infrared bands are also found at 2904, 3105, 3307, 3453 and
      3523 cm(-1) and are attributed to water. Raman spectroscopy complimented with
      infrared spectroscopy has enabled aspects of the structure of kapundaite to be
      ascertained and compared with that of other phosphate minerals.

PMID- 24317267
TI  - Inclusion complexation of isoprenaline and methyl dopa with alpha- and beta
      cyclodextrin nanocavities: spectral and theoretical study.
AB  - Inclusion complex formation of isoprenaline (ISOP) and methyldopa (MDOP) with
      alpha-CD and beta-CD were investigated. Solid inclusion complex nanomaterials
      were characterized by SEM, TEM, FTIR, DSC, (1)H NMR and XRD methods. Spectral
      results showed that single emission (monomer) noticed in aqueous solution where
      as dual emission (excimer) in CD. Both drugs formed 1:2 (CD-drug2) inclusion
      complexes with CDs. Time-resolved fluorescence studies show that single
      exponential decay observed in water whereas biexponential decay observed in CD.
      Nano-sized particles were found in ISOP/CD while vesicles were obtained in
      MDOP/CD complexes. DSC results revealed that the thermal stability of drugs was
      improved when it was included in the CD nanocavity. Based on PM3 calculations,
      the inclusion structure of ISOP/CD and MDOP/CD complexes were proposed.
      Thermodynamic parameters and binding affinity of complexation of CD were
      determined by PM3 method.

PMID- 24317268
TI  - Notch2 transduction by feline leukemia virus in a naturally infected cat.
AB  - Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in
      cats. The transduction of cellular genes by FeLV is sometimes observed and
      associated with neoplastic diseases including lymphoma and sarcoma. Here, we
      report the first natural case of feline Notch2 transduction by FeLV in an
      infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant
      FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of
      a reporter gene, similar to what was previously reported in cats with
      experimental FeLV-induced thymic lymphoma. Our findings suggest that the
      transduction of Notch2 strongly correlates with FeLV-induced lymphoma. 

PMID- 24317269
TI  - Two distinct mtDNA lineages among captive African penguins in Japan.
AB  - The African penguin (Spheniscus demersus) is one of the world's most endangered
      seabirds. In Japan, although the number of African penguins in captivity
      continues to increase, genetic data have not been collected for either wild or
      captive populations. To reveal genetic diversity and characterization in captive
      African penguins, we analyzed the nucleotide sequences of mitochondrial DNA
      (mtDNA) from a sample of 236 African penguins. Analysis of 433 bp of the control
      region and 1,140 bp of cytochrome b sequences revealed the existence of two mtDNA
      clades. Control region haplotypes were much more divergent (d=3.39%) between the
      two clades than within each clade. The divergence of these clades may reflect
      differences at the subspecies or geographical population level in African
      penguins. These findings suggest that at least two distinct maternal lineages
      exist in the wild populations of the African penguin. 

PMID- 24317270
TI  - Killing cancer cells, twice with one shot.

PMID- 24317271
TI  - Dying from within: granzyme B converts entosis to emperitosis.

PMID- 24317272
TI  - Identification of natural splice variants of SAMHD1 in virus-infected HCC.
AB  - It has been previously shown that the sterile alpha motif domain and HD domain
      containing protein 1 (SAMHD1) can act as a retroviral restriction factor by
      inhibiting HIV-1 infection, but whether it has any roles in cancer is still
      unclear. In the present study, we identified several SAMHD1 splice variants
      naturally occurring in liver cancer and investigated their roles in regulating
      drug susceptibility. SAMHD1 variants were identified by sequencing. RT-PCR and
      western blot analysis were performed to verify the expression level of the
      polymorphisms. Cell cycle analysis was carried out using flow cytometry, and data
      were analyzed using Multicycle software. Several deletions of SAMHD1 were
      identified in both the patients and the healthy controls with no significant
      difference in respective frequencies, while an insertion in the exon4 occurred at
      a higher frequency in HBV- and HCV-infected patients (36.4 and 30%, respectively)
      when compared to the control groups. Following cisplatin treatment and cell cycle
      analysis, SAMHD1 variants showed different activities in increasing the
      susceptibility to chemotherapy drugs. The insertion of exon4 correlated with the
      occurrence of virus infection in the HCC patients. In conclusion, analysis of the
      different activities of SAMHD1 splice variants in regulating drug sensitivity
      implied that the exon4 insertion might act as an indicator of the occurrence of
      liver cancer.

PMID- 24317273
TI  - Vasorelaxing and antihypertensive effects of 7,8-dihydroxyflavone.
AB  - BACKGROUND: Although 7,8-dihydroxyflavone (7,8-DHF) has been demonstrated to be
      potently neuroprotective, its effect on vascular function remains unknown.
      METHODS: The effect of 7,8-DHF on phenylephrine (PE)-induced preconstriction was
      examined with aortic rings isolated from normal rats. Its effective mechanisms
      were studied with blockers, Western blotting, and primarily cultured vascular
      smooth myocytes. The blood pressure (BP) of rats was measured with a tail cuff
      method. RESULTS: 7,8-DHF dose-dependently dilated the PE-preconstricted,
      endothelia-intact aortic rings with concentration for 50% of maximal effect
      (EC50) of approximately 24 uM. Both Nomega-nitro-L-arginine methyl ester
      hydrochloride, a nitric oxide synthase inhibitor, and 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one, a soluble guanylyl cyclase blocker, significantly reduced the
      vasorelaxing effect of 7,8-DHF. Western blotting showed that 7,8-DHF increased
      the aortic endothelial nitric oxide synthase protein expression and
      phosphorylation. With endothelia removed, 7,8-DHF also dilated the PE
      preconstricted rings but with EC50 of approximately 104 uM. Ca(2+) imaging
      experiments detected that 7,8-DHF probably blocked both intracellular Ca(2+)
      release and extracellular Ca(2+) influx. Therefore, the mechanisms of 7,8-DHF
      dilating effect might be stimulating the nitric oxide/cGMP production and
      blocking the Ca(2+) signaling pathway instead of tropomyosin receptor kinase B
      receptors because ANA-12, its specific antagonist, did not show any effect
      against 7,8-DHF. When administered intravenously, 7,8-DHF significantly reduced
      the BP of the spontaneously hypertensive rats. However, when used orally, there
      was only a slight but significant reduction in the diastolic pressure.
      CONCLUSIONS: The results suggest that neuro-protective 7,8-DHF is also a
      vasorelaxing and antihypertensive substance in rats.

PMID- 24317274
TI  - The influence of inaccuracies in carotid MRI segmentation on atherosclerotic
      plaque stress computations.
AB  - Biomechanical finite element analysis (FEA) based on in vivo carotid magnetic
      resonance imaging (MRI) can be used to assess carotid plaque vulnerability
      noninvasively by computing peak cap stress. However, the accuracy of MRI plaque
      segmentation and the influence this has on FEA has remained unreported due to the
      lack of a reliable submillimeter ground truth. In this study, we quantify this
      influence using novel numerical simulations of carotid MRI. Histological sections
      from carotid plaques from 12 patients were used to create 33 ground truth plaque
      models. These models were subjected to numerical computer simulations of a
      currently used clinically applied 3.0 T T1-weighted black-blood carotid MRI
      protocol (in-plane acquisition voxel size of 0.62 * 0.62 mm2) to generate
      simulated in vivo MR images from a known underlying ground truth. The simulated
      images were manually segmented by three MRI readers. FEA models based on the MRI
      segmentations were compared with the FEA models based on the ground truth. MRI
      based FEA model peak cap stress was consistently underestimated, but still
      correlated (R) moderately with the ground truth stress: R = 0.71, R = 0.47, and R
      = 0.76 for the three MRI readers respectively (p < 0.01). Peak plaque stretch was
      underestimated as well. The peak cap stress in thick-cap, low stress plaques was
      substantially more accurately and precisely predicted (error of -12 +/- 44 kPa)
      than the peak cap stress in plaques with caps thinner than the acquisition voxel
      size (error of -177 +/- 168 kPa). For reliable MRI-based FEA to compute the peak
      cap stress of carotid plaques with thin caps, the current clinically used in
      plane acquisition voxel size (~0.6 mm) is inadequate. FEA plaque stress
      computations would be considerably more reliable if they would be used to
      identify thick-cap carotid plaques with low stresses instead. 

PMID- 24317275
TI  - Acute type-A aortic dissection with patent false lumen through to the abdominal
      aorta: effects of a conventional elephant trunk on malperfusion syndromes and
      narrowed true lumen.
AB  - BACKGROUND: Narrowed true lumen and patent false lumen through to the terminal
      aorta is a high-risk condition for malperfusion syndromes (MS) in acute type-A
      aortic dissection. It is important to ascertain how the true and false lumens
      behave after surgery. PATIENTS AND METHODS: We retrospectively investigated 45
      patients with this pathology. The true lumen sizes at the narrowest levels above
      and below the superior mesenteric artery were followed by computed tomography
      after surgery (0-36 months). RESULTS: Thirty-seven MS were seen in 23 patients.
      Hospital mortality was 8.9%. The narrowed true lumen was not enlarged in the
      first 6 months with a patent false lumen. The elephant trunk procedure did not
      improve the true lumen size. An extremely narrowed (<=3 mm) true lumen was
      associated with a significantly high incidence of MS and mortality. CONCLUSIONS:
      High incidences of MS were observed in this particular pathology. An extremely
      narrowed true lumen was accompanied by a high incidence of MS and mortality.

PMID- 24317276
TI  - Fluorescent macrocyclic probes with pendant functional groups as markers of
      acidic organelles within live cells.
AB  - A new family of acidity sensitive fluorescent macrocycles has been synthesized
      and fully characterized. Their photophysical properties including emission
      quantum yield and fluorescence lifetime have been determined. The acid-base
      properties of the new molecules can be tuned by the incorporation of pendant
      functional groups. The nature of such functional groups (carboxylic acid or
      ester) influences dramatically the pKa of the probes, two compounds of which
      exhibit low values. Preliminary intracellular studies using confocal microscopy
      together with emission spectra of the probes from the cellular environment have
      shown that the synthesized fluorescent macrocycles mark the acidic organelles of
      RAW 264.7 macrophage cells. 

PMID- 24317277
TI  - From assembled metal-organic framework nanoparticles to hierarchically porous
      carbon for electrochemical energy storage.
AB  - Meso-/macropores have been induced as additional second-order structures by the
      assembly of particles of a microporous zeolitic imidazolate framework, ZIF-8,
      prepared by ultrasonication. Simple carbonization of ZIF-8 affords a 3
      dimensional hierarchically porous carbon framework with micro-, meso- and
      macropores, which exhibits the best performance ever reported as a supercapacitor
      electrode. 

PMID- 24317278
TI  - Interaction of Shiga toxin 2 with complement regulators of the factor H protein
      family.
AB  - Shiga toxin 2 (Stx2) is believed to be a major virulence factor of
      enterohemorrhagic Escherichia coli (EHEC) contributing to hemolytic uremic
      syndrome (HUS). The complement system has recently been found to be involved in
      the pathogenesis of EHEC-associated HUS. Stx2 was shown to activate complement
      via the alternative pathway, to bind factor H (FH) at short consensus repeats
      (SCRs) 6-8 and 18-20 and to delay and reduce FH cofactor activity on the cell
      surface. We now show that complement factor H-related protein 1 (FHR-1) and
      factor H-like protein 1 (FHL-1), proteins of the FH protein family that show
      amino acid sequence and regulatory function similarities with FH, also bind to
      Stx2. The FHR-1 binding site for Stx2 was located at SCRs 3-5 and the binding
      capacity of FHR-1*A allotype was higher than that of FHR-1*B. FHR-1 and FHL-1
      competed with FH for Stx2 binding, and in the case of FHR-1 this competition
      resulted in a reduction of FH cofactor activity. FHL-1 retained its cofactor
      activity in the fluid phase when bound to Stx2. In conclusion, multiple
      interactions of key complement inhibitors FH, FHR-1 and FHL-1 with Stx2
      corroborate our hypothesis of a direct role of complement in EHEC-associated HUS.

PMID- 24317279
TI  - Dogs infected with the blood trypomastigote form of Trypanosoma cruzi display an
      increase expression of cytokines and chemokines plus an intense cardiac
      parasitism during acute infection.
AB  - The recent increase in immigration of people from areas endemic for Chagas
      disease (Trypanosoma cruzi) to the United States and Europe has raised concerns
      about the transmission via blood transfusion and organ transplants in these
      countries. Infection by these pathways occurs through blood trypomastigotes (BT),
      and these forms of T. cruzi are completely distinct of metacyclic trypomastigotes
      (MT), released by triatomine vector, in relation to parasite-host interaction.
      Thus, research comparing infection with these different infective forms is
      important for explaining the potential impacts on the disease course. Here, we
      investigated tissue parasitism and relative mRNA expression of cytokines,
      chemokines, and chemokine receptors in the heart during acute infection by MT or
      BT forms in dogs. BT-infected dogs presented a higher cardiac parasitism,
      increased relative mRNA expression of pro-inflammatory and immunomodulatory
      cytokines and of the chemokines CCL3/MIP-1alpha, CCL5/RANTES, and the chemokine
      receptor CCR5 during the acute phase of infection, as compared to MT-infected
      dogs. These results suggest that infection with BT forms may lead to an increased
      immune response, as revealed by the cytokines ratio, but this kind of immune
      response was not able to control the cardiac parasitism. Infection with the MT
      form presented an increase in the relative mRNA expression of IL-12p40 as
      compared to that of IL-10 or TGF-beta1. Correlation analysis showed increased
      relative mRNA expression of IFN-gamma as well as IL-10, which may be an
      immunomodulatory response, as well as an increase in the correlation of
      CCL5/RANTES and its CCR5 receptor. Our findings revealed a difference between
      inoculum sources of T. cruzi, as vectorial or transfusional routes of T. cruzi
      infection may trigger distinct parasite-host interactions during the acute phase,
      which may influence immunopathological aspects of Chagas disease. 

PMID- 24317280
TI  - Internal carotid artery thrombosis due to an unusual soft palate injury in a
      child.
AB  - Intraoral trauma is commonly observed in young children due to their tendency to
      put objects in their mouth. Most of these injuries are minor, without significant
      morbidity. However, potentially fatal injuries could occur after penetrating
      trauma to the oral cavity and could initially present with minor clinical
      findings. 

PMID- 24317281
TI  - Modifying social anxiety related to a real-life stressor using online Cognitive
      Bias Modification for interpretation.
AB  - Modifying threat related biases in attention and interpretation has been shown to
      successfully reduce global symptoms of anxiety in high anxious and clinically
      anxious samples (termed Cognitive Bias Modification, CBM). However, the
      possibility that CBM can be used as a way to prevent anxiety associated with an
      upcoming real-life stressful event in vulnerable populations has yet to be
      systematically examined. The present study aimed to assess whether a two-week
      course of online CBM for interpretations (CBM-I) could reduce social evaluative
      fear when starting university. Sixty-nine students anxious about starting
      university completed five sessions of online CBM in the two weeks prior to
      starting university, or completed a placebo control intervention. Results
      indicated that CBM-I reduced social evaluative fear from baseline to day one of
      starting university to a greater extent than the placebo control intervention.
      Also, there was a greater reduction in state anxiety and a trend indicating a
      greater reduction in social evaluative fear in the CBM-I group at 4 weeks follow
      up. Results suggest that CBM-I could be used as a preventative tool to help
      reduce anxiety specific to challenging life events. 

PMID- 24317283
TI  - Molecular-sized fluorescent nanodiamonds.
AB  - Doping of carbon nanoparticles with impurity atoms is central to their
      application. However, doping has proven elusive for very small carbon
      nanoparticles because of their limited availability and a lack of fundamental
      understanding of impurity stability in such nanostructures. Here, we show that
      isolated diamond nanoparticles as small as 1.6 nm, comprising only ~400 carbon
      atoms, are capable of housing stable photoluminescent colour centres, namely the
      silicon vacancy (SiV). Surprisingly, fluorescence from SiVs is stable over time,
      and few or only single colour centres are found per nanocrystal. We also observe
      size-dependent SiV emission supported by quantum-chemical simulation of SiV
      energy levels in small nanodiamonds. Our work opens the way to investigating the
      physics and chemistry of molecular-sized cubic carbon clusters and promises the
      application of ultrasmall non-perturbative fluorescent nanoparticles as markers
      in microscopy and sensing. 

PMID- 24317284
TI  - A synthetic DNA motor that transports nanoparticles along carbon nanotubes.
AB  - Intracellular protein motors have evolved to perform specific tasks critical to
      the function of cells such as intracellular trafficking and cell division.
      Kinesin and dynein motors, for example, transport cargoes in living cells by
      walking along microtubules powered by adenosine triphosphate hydrolysis. These
      motors can make discrete 8 nm centre-of-mass steps and can travel over 1 um by
      changing their conformations during the course of adenosine triphosphate binding,
      hydrolysis and product release. Inspired by such biological machines, synthetic
      analogues have been developed including self-assembled DNA walkers that can make
      stepwise movements on RNA/DNA substrates or can function as programmable assembly
      lines. Here, we show that motors based on RNA-cleaving DNA enzymes can transport
      nanoparticle cargoes-CdS nanocrystals in this case-along single-walled carbon
      nanotubes. Our motors extract chemical energy from RNA molecules decorated on the
      nanotubes and use that energy to fuel autonomous, processive walking through a
      series of conformational changes along the one-dimensional track. The walking is
      controllable and adapts to changes in the local environment, which allows us to
      remotely direct 'go' and 'stop' actions. The translocation of individual motors
      can be visualized in real time using the visible fluorescence of the cargo
      nanoparticle and the near-infared emission of the carbon-nanotube track. We
      observed unidirectional movements of the molecular motors over 3 um with a
      translocation velocity on the order of 1 nm min(-1) under our experimental
      conditions. 

PMID- 24317285
TI  - Control of single-spin magnetic anisotropy by exchange coupling.
AB  - The properties of quantum systems interacting with their environment, commonly
      called open quantum systems, can be affected strongly by this interaction.
      Although this can lead to unwanted consequences, such as causing decoherence in
      qubits used for quantum computation, it can also be exploited as a probe of the
      environment. For example, magnetic resonance imaging is based on the dependence
      of the spin relaxation times of protons in water molecules in a host's tissue.
      Here we show that the excitation energy of a single spin, which is determined by
      magnetocrystalline anisotropy and controls its stability and suitability for use
      in magnetic data-storage devices, can be modified by varying the exchange
      coupling of the spin to a nearby conductive electrode. Using scanning tunnelling
      microscopy and spectroscopy, we observe variations up to a factor of two of the
      spin excitation energies of individual atoms as the strength of the spin's
      coupling to the surrounding electronic bath changes. These observations, combined
      with calculations, show that exchange coupling can strongly modify the magnetic
      anisotropy. This system is thus one of the few open quantum systems in which the
      energy levels, and not just the excited-state lifetimes, can be renormalized
      controllably. Furthermore, we demonstrate that the magnetocrystalline anisotropy,
      a property normally determined by the local structure around a spin, can be tuned
      electronically. These effects may play a significant role in the development of
      spintronic devices in which an individual magnetic atom or molecule is coupled to
      conducting leads. 

PMID- 24317286
TI  - Predictive performance of universal termination of resuscitation rules in an
      Asian community: are they accurate enough?
AB  - INTRODUCTION: Prehospital termination of resuscitation (TOR) rules have not been
      widely validated outside of Western countries. This study evaluated the
      performance of TOR rules in an Asian metropolitan with a mixed-tier emergency
      medical service (EMS). METHODS: We analysed the Utstein registry of adult, non
      traumatic out-of-hospital cardiac arrests (OHCAs) in Taipei to test the
      performance of TOR rules for advanced life support (ALS) or basic life support
      (BLS) providers. ALS and BLS-TOR rules were tested in OHCAs among three
      subgroups: (1) resuscitated by ALS, (2) by BLS and (3) by mixed ALS and BLS.
      Outcome definition was in-hospital death. Sensitivity, specificity, positive
      predictive value (PPV), negative predictive value and decreased transport rate
      (DTR) among various provider combinations were calculated. RESULTS: Of the 3489
      OHCAs included, 240 were resuscitated by ALS, 1727 by BLS and 1522 by ALS and
      BLS. Overall survival to hospital discharge was 197 patients (5.6%). Specificity
      and PPV of ALS-TOR and BLS-TOR for identifying death ranged from 70.7% to 81.8%
      and 95.1% to 98.1%, respectively. Applying the TOR rules would have a DTR of 34.2
      63.9%. BLS rules had better predictive accuracy and DTR than ALS rules among all
      subgroups. CONCLUSIONS: Application of the ALS and BLS TOR rules would have
      decreased OHCA transported to the hospital, and BLS rules are reasonable as the
      universal criteria in a mixed-tier EMS. However, 1.9-4.9% of those who survived
      would be misclassified as non-survivors, raising concern of compromising patient
      safety for the implementation of the rules.

PMID- 24317287
TI  - Is there a diurnal difference in mortality of severely injured trauma patients?
AB  - BACKGROUND: Mortality may be higher for admissions at odd hours than during
      daytime, although for trauma patients results are conflicting. The objective of
      this study was to assess whether diurnal differences in mortality among severely
      injured trauma patients in Denmark were present. METHODS: This observational
      cohort study was conducted between 1 December 2009 and 30 April 2011 involving
      one level 1 trauma centre and seven local emergency departments in eastern
      Denmark. Patients were consecutively included if received by a designated trauma
      team. Night-time patients (20:00-07:59) were compared with daytime patients
      (20:00-07:59). An injury severity score (ISS) >15 defined severe injury. Patients
      with burns and patients who upon arrival were declared non-trauma patients were
      not included. The primary outcome measure was 30-day mortality. RESULTS: A total
      of 1985 patients were recorded, of whom 576 were admitted at night-time, 1369 at
      daytime and 40 not included due to missing data. There were 142 patients with ISS
      >15 in the daytime group and 64 at night-time. The 30-day mortality was 14.1% for
      admittance at night-time versus 21.3% at daytime (p=0.22). Logistic regression
      analysis revealed that odd-hour admission was not a significant predictor of
      mortality for patients with ISS >15 when adjusted for age, ISS and initial
      treatment facility (OR 0.71 (95% CI 0.27 to 1.90); p=0.50). CONCLUSIONS: In
      conclusion, we found no diurnal differences in 30-day mortality for severely
      injured trauma patients.

PMID- 24317288
TI  - The pecking order.
AB  - This paper explores the idea that courtesy and respect between health
      professionals at each stage of the admission process of a patient to hospital
      would make life much easier and more pleasant for all staff. 

PMID- 24317289
TI  - Cervical necrotising fasciitis with descending mediastinitis.

PMID- 24317290
TI  - Management of Bell's palsy in children: an audit of current practice, review of
      the literature and a proposed management algorithm.
AB  - OBJECTIVE: We carried out a complete audit cycle, reviewing our management of
      paediatric patients with Bell's palsy within 72 h of symptom onset. Our protocol
      was published after the initial audit in 2009, and a re-audit was carried out in
      2011. We aimed to improve our current practice in accordance with up-to-date
      evidence-based research on the use of steroids and antivirals. PATIENTS AND
      METHODS: A total of 17 patients were included in the first cycle, but only eight
      patients met our inclusion and exclusion criteria for the re-audit. We assessed
      documentation of House-Brackmann (HB) grade on presentation, initial treatment,
      follow-up and recovery. RESULTS: The first cycle revealed inconsistent management
      with steroids (41%), antivirals (6%), steroids and antivirals (6%) or nothing at
      all (47%). In addition, only 65% of patients were followed-up in the ear, nose
      and throat (ENT) clinic. Our management protocol was published in 2010, and a re
      audit was completed. Our results showed 100% compliance with steroid treatment
      and 100% follow-up with the ENT team. A thorough literature review revealed some
      additional benefit from the use of antivirals. CONCLUSIONS: At present there is
      insufficient evidence to discount the use of steroids and antivirals. Therefore,
      with our new management protocol, we recommend the use of steroids in patients
      presenting within 72 h of symptom onset, and antivirals for patients with a HB
      grade of IV or higher.

PMID- 24317291
TI  - The value of retinal imaging with infrared scanning laser ophthalmoscopy in
      patients with stargardt disease.
AB  - PURPOSE: To demonstrate the value of infrared scanning laser ophthalmoscopy (SLO)
      for determining structural retinal and choroidal changes in patients with
      Stargardt disease and its comparison to findings on short-wavelength fundus
      autofluorescence (SW-AF) imaging, spectral-domain optical coherence tomography,
      and microperimetry measurements. METHODS: Forty-four eyes of 22 patients with
      Stargardt disease were studied using infrared-SLO, spectral-domain optical
      coherence tomography, macular microperimetry, SW-AF, electroretinography, and
      fundus photography. RESULTS: Although SW-AF imaging outlined the regions of
      retinal pigment epithelial (RPE) atrophy (hypofluorescence) and enhanced the
      visibility of more funduscopically apparent flecks (hyperfluorescence), infrared
      SLO imaging outlined the regions of choroidal, and RPE, atrophic changes.
      Degenerative changes in photoreceptor and RPE cell layers, evident on spectral
      domain optical coherence tomography imaging, were associated with either
      hyporeflective or hyperreflective images on infrared-SLO imaging, depending on
      whether both RPE and choroidal atrophy (hyperreflectance) or solely RPE atrophy
      (hyporeflectance) was present. Threshold elevations on microperimetry testing
      corresponded to both RPE and choroidal atrophy on infrared-SLO imaging and RPE
      atrophy on SW-AF. CONCLUSION: Although SW-AF identifies regions of RPE atrophy,
      infrared-SLO also identifies the involvement of the choroid that has important
      implications for the potential improvement in visual function from treatment.
      Thus, infrared-SLO imaging offers an additional advantage beyond that obtained
      with SW-AF.

PMID- 24317292
TI  - No cases of endophthalmitis after 20,293 intravitreal injections in an operating
      room setting.
AB  - BACKGROUND: Intravitreal injection has become a common procedure worldwide. A
      rare, but sight threatening, complication is bacterial endophthalmitis that has a
      poor visual prognosis. To identify practices that minimize the risk of
      endophthalmitis, the setting of a Danish University hospital is described.
      METHODS: A review of the intravitreal injection database of the department. All
      injections were performed in a positive pressure ventilated operating room under
      sterile conditions. The treating physicians wore face mask, the conjunctiva was
      irrigated twice with 5% povidone-iodine preoperatively, and topical tobramycin
      was applied immediately after the injection. RESULTS: The authors have performed
      a total of 20,293 injections were performed in 2,575 eyes. No cases of proven or
      suspected endophthalmitis were identified corresponding to a risk of 0% (95%
      confidence interval, 0-0.019) per injection and 0% (95% confidence interval, 0
      0.15%) per patient. Approximately 7,000 injections, all in patients without
      diabetes, were treated without a course of topical antibiotics after the
      injection. CONCLUSION: The department has had the lowest rate of endophthalmitis
      after intravitreal injections in the current literature. Several factors that
      could have contributed to the positive result are highlighted. Omitting a
      postoperative course of topical antibiotic appears safe in patients without
      diabetes.

PMID- 24317293
TI  - Primary posterior capsulotomy and posterior optic buttonholing in eyes with
      phacovitrectomy and gas tamponade.

PMID- 24317294
TI  - Intraoperative PTH monitoring: a new approach based on the identification of the
      "true" time origin of the decay curve.
AB  - Some published criteria for intraoperative monitoring of PTH serum concentrations
      may cause misleading results, since the timing of samples measured between the
      pre-incision and pre-excision phase of surgery is often unrecorded. In our
      opinion this information is critical, as the time of an intermediate sample
      during surgical manipulation may represent the "true" beginning of the PTH decay.
      We modified the usual criterion of monitoring (cut-off at 10 minutes after
      clamping) proposing a further check at manipulation in case the primary check at
      clamping produces an apparently negative result. On the basis of a mathematical
      model, false negative curves were simulated by means of a time shift. This shift
      was assumed to be the interval between manipulation and clamping. Analysing the
      decay curve, we used the 50% cut-off at 10 minutes after the supposed "true"
      origin (clamping or manipulation). Using a rapid immunochemiluminometric assay
      (ICMA), data were collected from 22 patients successfully operated for
      parathyroid adenoma. The check at clamping correctly diagnosed 13 patients. Among
      the 9 false negative cases, 6 were correctly diagnosed considering the
      manipulation as the baseline value. In the remaining 3 patients, diagnosis
      required prolonged observation of the curves. In case the iPTH decay does not
      follow the expected curve, it can be useful to check the decay normalising to a
      pre-excision value. The advantages of our criterion are both the prompt
      recognition of false negative results and the construction of a "true" decay
      curve for each patient, supporting the surgeon during the excision of
      hyperfunctioning parathyroid tissue. 

PMID- 24317295
TI  - Photobleaching imprinting microscopy: seeing clearer and deeper.
AB  - We present a generic sub-diffraction-limited imaging method - photobleaching
      imprinting microscopy (PIM) - for biological fluorescence imaging. A lateral
      resolution of 110 nm was measured, more than a twofold improvement over the
      optical diffraction limit. Unlike other super-resolution imaging techniques, PIM
      does not require complicated illumination modules or specific fluorescent dyes.
      PIM is expected to facilitate the conversion of super-resolution imaging into a
      routine lab tool, making it accessible to a much broader biological research
      community. Moreover, we show that PIM can increase the image contrast of
      biological tissue, effectively extending the fundamental depth limit of multi
      photon fluorescence microscopy. 

PMID- 24317296
TI  - ICAM-2 facilitates luminal interactions between neutrophils and endothelial cells
      in vivo.
AB  - Intercellular adhesion molecule 2 (ICAM-2) is expressed on endothelial cells
      (ECs) and supports neutrophil extravasation. However, the full details of its
      role remain unknown, and the present study investigates the functional mechanisms
      of ICAM-2 in neutrophil-endothelial-cell interactions. Our initial studies showed
      expression of ICAM-2 at both EC junctions and on the EC body. In line with the
      observed expression profile analysis of neutrophil-vessel-wall interactions using
      real-time in vivo confocal microscopy identified numerous functional roles for
      ICAM-2 within the vascular lumen and at the stage of neutrophil extravasation.
      Functional or genetic blockade of ICAM-2 significantly reduced neutrophil
      crawling velocity, increased frequency of crawling with a disrupted stop-start
      profile, and prolonged interaction of neutrophils with EC junctions prior to
      transendothelial cell migration (TEM), collectively resulting in significantly
      reduced extravasation. Pharmacological blockade of the leukocyte integrin MAC-1
      indicated that some ICAM-2-dependent functions might be mediated through ligation
      of this integrin. These findings highlight novel roles for ICAM-2 in mediating
      luminal neutrophil crawling and the effect on subsequent levels of extravasation.

PMID- 24317297
TI  - Problems, needs, and useful strategies in older adults self-managing epilepsy:
      implications for patient education and future intervention programs.
AB  - OBJECTIVE: The purpose of this study was to determine, in a sample of older
      adults diagnosed with epilepsy, perceived self-management problems and needs
      encountered since diagnosis, as well as strategies used to address problems and
      needs. METHODS: Qualitative description was used. Twenty older adults engaged in
      face-to-face interviews. Interviews were analyzed via content analysis. RESULTS:
      Participants reported problems, needs, and strategies in six categories:
      Information, Physical and Emotional Symptoms, Memory and Concentration,
      Medications, Commitments, and Relationships. CONCLUSION: Participants noted some
      problems and needs previously documented in the literature, though current
      results have built upon extant literature to reveal etiologies of and contexts
      surrounding problems and needs; new findings were also revealed. This knowledge
      can be used by health-care providers in counseling and educating older adults
      with epilepsy and can inform formal self-management interventions. PRACTICE
      IMPLICATIONS: Determining needs from the patient's perspective is consistent with
      today's focus on patient-centered care. Current findings have led to an
      organizing framework for problems and needs of older adults with epilepsy. More
      research is needed to develop the framework so that it can serve as a template
      for an intervention. In the interim, findings can inform educational practices of
      those caring for this population.

PMID- 24317298
TI  - Agent-based modeling traction force mediated compaction of cell-populated
      collagen gels using physically realistic fibril mechanics.
AB  - Agent-based modeling was used to model collagen fibrils, composed of a string of
      nodes serially connected by links that act as Hookean springs. Bending mechanics
      are implemented as torsional springs that act upon each set of three serially
      connected nodes as a linear function of angular deflection about the central
      node. These fibrils were evaluated under conditions that simulated axial
      extension, simple three-point bending and an end-loaded cantilever. The
      deformation of fibrils under axial loading varied <0.001% from the analytical
      solution for linearly elastic fibrils. For fibrils between 100 MUm and 200 MUm in
      length experiencing small deflections, differences between simulated deflections
      and their analytical solutions were <1% for fibrils experiencing three-point
      bending and <7% for fibrils experiencing cantilever bending. When these new rules
      for fibril mechanics were introduced into a model that allowed for cross-linking
      of fibrils to form a network and the application of cell traction force, the
      fibrous network underwent macroscopic compaction and aligned between cells.
      Further, fibril density increased between cells to a greater extent than that
      observed macroscopically and appeared similar to matrical tracks that have been
      observed experimentally in cell-populated collagen gels. This behavior is
      consistent with observations in previous versions of the model that did not allow
      for the physically realistic simulation of fibril mechanics. The significance of
      the torsional spring constant value was then explored to determine its impact on
      remodeling of the simulated fibrous network. Although a stronger torsional spring
      constant reduced the degree of quantitative remodeling that occurred, the
      inclusion of torsional springs in the model was not necessary for the model to
      reproduce key qualitative aspects of remodeling, indicating that the presence of
      Hookean springs is essential for this behavior. These results suggest that
      traction force mediated matrix remodeling may be a robust phenomenon not limited
      to fibrils with a precise set of material properties. 

PMID- 24317299
TI  - Giant amino acids designed on the polysaccharide scaffold and their protein-like
      structural interconversion.
AB  - Amphoteric beta-1,3-glucans possessing both amino groups and carboxylic acid
      groups on the C6 positions of glucose units were designed and synthesized from
      naturally produced curdlan. The amphoteric polysaccharides showed the isoelectric
      point and the pH responsive interconversion between the original triple helix and
      single-stranded random structures. Since the pH dependences are comparable to the
      typical properties of proteins, the polysaccharides can be considered as a new
      class of giant amino acids. Utilizing the pH responsiveness, pH-controlled catch
      and-release has been realized for cationic peptides or anionic DNA. We believe
      that the amphoteric polysaccharide can act as a new potential polymer to
      construct stimuli-responsive smart materials on the basis of the polysaccharide
      scaffold. 

PMID- 24317300
TI  - [Spontaneous bacterial peritonitis in Dakar, Senegal: study of 55 patients with
      cirrhosis].
AB  - OBJECTIVES: To report the prevalence of spontaneous bacterial peritonitis (SBP)
      and its clinical and laboratory features in patients with cirrhosis followed at
      the Aristide Le Dantec Hospital in Dakar (Senegal). PATIENTS AND METHODS: From
      May through December, 2010, we prospectively included patients with cirrhosis and
      a first episode of ascites on clinical examination. Diagnostic abdominal
      paracentesis was performed in all cases to determine the macroscopic appearance
      of the fluid, protein concentration, and cell count, and to culture the ascitic
      fluid in a blood culture bottle. SBP was diagnosed when the fluid contained more
      than 250 polymorphonuclear leukocytes per cubic millimeter of fluid. The data
      were analyzed with Epi-Info software, version 3.5.2. Comparisons used Fisher's
      exact and Chi-square tests, with significance set at p < 0.05. RESULTS: The study
      included 55 patients with cirrhosis, with a mean age of 45 years and a
      male/female sex ratio of 1.89 (36 men). The prevalence of SBP was 27.3%. Factors
      significantly associated with SBP were female gender, malnutrition, turbid
      appearance of the ascites, and neutrophilia. In samples from patients with SBP,
      the mean protein concentration was 20.7 g/L, the white cell count was 1797/mm(3),
      and the neutrophil count 1,102/mm(3). Ascitic fluid culture was positive in 20%
      of the SBP cases (n=3). CONCLUSION: In Dakar, cirrhosis is found especially in
      young adults, and the prevalence of SBP in our population was 27.3%. Improved
      technical equipment would improve the hospital's ability to determine the causes
      of cirrhosis and identify the various germs responsible for SBP.

PMID- 24317302
TI  - [Report on notifications according to section 8d of the German Transplantation
      Act (TPG) for the years 2009-2011].
AB  - In Germany, the Tissue Act came into effect on 1 August 2007. Since then, every
      tissue establishment is legally obligated to keep a record of its activities
      according to section 8d subsection 3 of the Transplantation Act (TPG). An annual
      report must be submitted to the Paul Ehrlich Institute once a year up to 1 March
      of the subsequent year. The report should include the types and quantities of
      tissues procured, conditioned, processed, stored, distributed or otherwise
      disposed of, imported, and exported. The report should be made on a TPG-based
      notification form published on the Internet by the Paul Ehrlich Institute. The
      present report according to section 8d subsection 3 of the TPG is based on data
      of the reporting years 2009-2011. Six years after implementation of the TPG's
      reporting obligation for tissue establishments, the number of tissue
      establishments known by the Paul Ehrlich Institute has increased from 349 in 2007
      to 949 in 2011. In the course of continuous optimization of the notification
      forms, including tissue-specific glossaries, the reported data of most of the
      tissues and tissue preparations have become more conclusive. 

PMID- 24317303
TI  - Kinetic stabilization against the oxidation reaction induced by a silaalkane cage
      in a thiophene-bridged molecular gyroscope.
AB  - Macrocage molecules with a bridged rotor have been synthesized as molecular
      gyroscopes. The kinetics of the oxidation reaction of the thiophene-bridged
      molecular gyroscope, whose thiophene ring was bridged inside a silaalkane cage,
      was investigated. A remarkable kinetic stabilization against the oxidation of the
      thiophene moiety induced by the molecular cage framework was observed. 

PMID- 24317301
TI  - Toll-like receptor 4-mediated signaling regulates IL-7-driven proliferation and
      differentiation of B-cell precursors.
AB  - Lipopolysaccharide (LPS) is known to be a potent activator of mature B cells by
      signaling through Toll-like receptor 4 (TLR4). Its impact on early B-cell
      development, however, is not well defined. When comparing to C3H/HeN mice, TLR4
      mutant C3H/HeJ mice showed an increase in the number of pro-B and pre-B cells in
      the bone marrow. When cultured in the presence of IL-7, the proliferation of pro
      B and large pre-B cells was significantly inhibited by LPS, possibly due to
      reduced IL-7 receptor-alpha (IL-7Ralpha) expression. Meanwhile, the generation of
      IgM(+)/IgD(+) B cells was greatly enhanced in IL-7 cultures of pro-B and pre-B
      cells. Consistent with these results, treatment with LPS facilitated the
      progression of adoptively transferred B220(+)IgM(-)IgD(-) precursors into IgD(+)
      cells. Overall, these data suggest that LPS has a profound influence on early B
      cell development, which may contribute to the deregulated B-cell development
      under physiological and pathological conditions such as bacterial infections. 

PMID- 24317304
TI  - Low serum vitamin D level is associated with high risk of metabolic syndrome in
      post-menopausal women.
AB  - BACKGROUND: Serum vitamin D status, as indicated by 25-(OH)D, is inversely
      associated with glucose homeostasis, lipid profiles, and blood pressure. Evidence
      on the association of serum vitamin D with metabolic syndrome (MS) however, is
      very limited in post-menopausal women. AIM: To investigate the association
      between serum vitamin D and MS. MATERIALS AND METHODS: This study was a
      crosssectional study including 778 Korean adults who visited a health promotion
      center in a university hospital from January 2010 to May 2011. MS was defined
      according to the American Heart Association/National Heart, Lung, and Blood
      Institute criteria and the Korean Society for the Study of Obesity. MS and its
      individual components were assessed, as well as serum 25-(OH)D levels with a
      multiple logistic regression analysis. RESULTS: The overall prevalence of the MS
      in participants of this study was 147 (18.9%). After multiple adjustments,
      compared with the highest quartile serum 25- (OH)D level group (19.9-55.9 ng/ml),
      the odds ratio for MS in the lowest level group (4.2-9.7 ng/ml) was 2.44 [95%
      confidence interval (CI)=1.32-4.48], in the lower level group (9.8- 14.1 ng/ml)
      was 2.20 (95% CI=1.24-3.90), and in the intermediate level group (14.3-19.8
      ng/ml) was 1.81 (95% CI=1.02-3.20). Among the components of MS, the adjusted odds
      ratios for having an elevated blood pressure, and high triglyceride level in the
      lowest level group were 1.81 (95% CI, 1.15-2.85), 2.74 (95% CI, 1.64-4.57),
      respectively. CONCLUSIONS: We found that a low serum 25-(OH)D level is
      significantly associated with the presence of MS and some metabolic components,
      especially the high triglyceride level and blood pressure in post-menopausal
      women.

PMID- 24317305
TI  - MicroRNAs: Suggested role in pituitary adenoma pathogenesis.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that represent a major
      class of molecular regulators. miRNAs have been implicated in the pathogenesis of
      several human tumors, including pituitary adenomas. Altered expression of miRNAs
      has been described in pituitary adenomas, and specific miRNA signatures are
      related to clinical and therapeutic characteristics of the tumors. The data
      suggest that miRNAs influence various genes known to be associated with the
      pathogenesis of pituitary adenomas and in this review we summarize these
      currently available studies focusing on miRNAs in pituitary adenomas. 

PMID- 24317308
TI  - Innovation in therapeutics development at the NCATS.

PMID- 24317307
TI  - Revitalizing psychiatric therapeutics.
AB  - Despite high prevalence and enormous unmet medical need, the pharmaceutical
      industry has recently de-emphasized neuropsychiatric disorders as 'too difficult'
      a challenge to warrant major investment. Here I describe major obstacles to drug
      discovery and development including a lack of new molecular targets, shortcomings
      of current animal models, and the lack of biomarkers for clinical trials. My
      major focus, however, is on new technologies and scientific approaches to
      neuropsychiatric disorders that give promise for revitalizing therapeutics and
      may thus answer industry's concerns. 

PMID- 24317309
TI  - Neurobiology of rapid acting antidepressants: role of BDNF and GSK-3beta.

PMID- 24317310
TI  - Seeing the future: epigenetic biomarkers of postpartum depression.

PMID- 24317311
TI  - Circuits in sync: decoding theta communication in fear and safety.

PMID- 24317312
TI  - Cell adhesion molecules: druggable targets for modulating the connectome and
      brain disorders?

PMID- 24317313
TI  - Toward identification of neural markers of suicide risk in adolescents.

PMID- 24317314
TI  - Reduced cocaine reinforcement in the male offspring of cocaine-experienced sires.

PMID- 24317315
TI  - De novo mutations in schizophrenia disrupt genes co-expressed in fetal prefrontal
      cortex.

PMID- 24317316
TI  - Repetitive transcranial magnetic stimulation as a treatment for auditory
      hallucinations.

PMID- 24317317
TI  - Parkinson's disease biomarkers: resources for discovery and validation.

PMID- 24317318
TI  - Error-related brain activity as a biomarker for cocaine relapse.

PMID- 24317319
TI  - Neurotherapeutic implications of brain-immune interactions.

PMID- 24317320
TI  - Neuronal primary cilia: an underappreciated signaling and sensory organelle in
      the brain.

PMID- 24317321
TI  - When synaptic proteins meet the genome: transcriptional regulation in cell death
      and plasticity by the synapto-nuclear messenger Jacob.

PMID- 24317322
TI  - Maintaining and modifying connections: roles for axon guidance cues in the mature
      nervous system.

PMID- 24317323
TI  - Functional selectivity at GPCRs: new opportunities in psychiatric drug discovery.

PMID- 24317324
TI  - Obesity, food, and addiction: emerging neuroscience and clinical and public
      health implications.

PMID- 24317325
TI  - Targeting emotion circuits with deep brain stimulation in refractory anorexia
      nervosa.

PMID- 24317326
TI  - Proteomic biomarkers for brain disorders: technical considerations and
      challenges.

PMID- 24317327
TI  - Recognizing hereditary colorectal cancer.
AB  - Colorectal cancer is the second-leading cause of cancer death in the United
      States. About 25% of patients have a personal or family history that suggests a
      hereditary colorectal cancer syndrome. This article describes the clinical and
      pathological characteristics of hereditary colorectal cancer, appropriate
      screening tests, and when to refer patients to a genetic counselor. 

PMID- 24317328
TI  - Not all antibodies are equal.
AB  - The epidermal growth factor receptor (EGFR) has been validated as a therapeutic
      target in several human tumors, including colorectal cancer (CRC).(1,2) Occupancy
      of the EGFR with ligand can activate the RAS/RAF/MAPK, STAT, and PI3K/AKT
      signaling pathways. These pathways modulate cellular proliferation, adhesion,
      angiogenesis, migration, and survival.(3) Anti-EGFR targeted antibodies, such as
      cetuximab and panitumumab, have shown response and disease stabilization rates of
      approximately 10% and 30%, respectively, when administered as monotherapy in
      CRC.(1,4) EGFR expression is used for patient selection for these studies.
      However, clinical results have suggested that the level of EGFR expression as
      measured by immunohistochemistry may not predict clinical benefit.(4,5)

PMID- 24317329
TI  - Synthesis and solvatochromism studies of novel bis(indolyl)methanes bearing
      functionalized arylthiophene groups as new colored materials.
AB  - The demand for dyes with solvatochromic properties has increased in the last few
      years, mainly due to their wide range of applications in the analytical and
      industrial fields, such as in the textile industry. The phenomenon of
      solvatochromism is associated with the differential solvation of the ground and
      excited states of the solvatochromic compounds, leading to an important tool for
      the study of the nature of solute-solvent interactions. In this paper we report
      the synthesis of new bis(indolyl)methane derivatives bearing arylthiophene
      spacers (2a-d) functionalized with electron-donating and electron-withdrawing
      groups, and the photophysical studies in different solvents, such as ethanol,
      acetonitrile, dichloromethane, trichloromethane, dimethylsulfoxide, diethylether
      and 1,4-dioxane. Aiming to explore their solvatochromic behaviour in the ground
      and excited states, all solvents employed have different hydrogen-bond donor
      abilities. The largest colour modifications were visualized for compound 2b, the
      solution colours of which are orange in DMSO, blue in trichloromethane, green in
      dichloromethane and purple in 1,4-dioxane. A negative solvatochromism was
      observed in 2b and a positive one in 2a, 2c and 2d. 

PMID- 24317331
TI  - Dose audit for patients undergoing two common radiography examinations with
      digital radiology systems.
AB  - PURPOSE: We aimed to determine the radiation doses delivered to patients
      undergoing general examinations using computed or digital radiography systems in
      Turkey. MATERIALS AND METHODS: Radiographs of 20 patients undergoing
      posteroanterior chest X-ray and of 20 patients undergoing anteroposterior kidney
      ureter-bladder radiography were evaluated in five X-ray rooms at four local
      hospitals in the Ankara region. Currently, almost all radiology departments in
      Turkey have switched from conventional radiography systems to computed
      radiography or digital radiography systems. Patient dose was measured for both
      systems. The results were compared with published diagnostic reference levels
      (DRLs) from the European Union and International Atomic Energy Agency. RESULTS:
      The average entrance surface doses (ESDs) for chest examinations exceeded
      established international DRLs at two of the X-ray rooms in a hospital with
      computed radiography. All of the other ESD measurements were approximately equal
      to or below the DRLs for both examinations in all of the remaining hospitals.
      Improper adjustment of the exposure parameters, uncalibrated automatic exposure
      control systems, and failure of the technologists to choose exposure parameters
      properly were problems we noticed during the study. CONCLUSION: This study is an
      initial attempt at establishing local DRL values for digital radiography systems,
      and will provide a benchmark so that the authorities can establish reference dose
      levels for diagnostic radiology in Turkey.

PMID- 24317332
TI  - The importance of craniovertebral and cervicomedullary angles in cervicogenic
      headache.
AB  - PURPOSE: Many studies have indicated that cervicogenic headache may originate
      from the cervical structures innervated by the upper cervical spinal nerves. To
      date, no study has investigated whether narrowing of the craniovertebral angle
      (CVA) or cervicomedullary angle (CMA) affects the three upper cervical spinal
      nerves. The aim of this study was to investigate the effect of CVA and/or CMA
      narrowing on the occurrence of cervicogenic headache. MATERIALS AND METHODS: Two
      hundred and five patients diagnosed with cervicogenic headache were included in
      the study. The pain scores of patients were determined using a visual analog
      scale. The nonheadache control group consisted of 40 volunteers. CVA and CMA
      values were measured on sagittal T2-weighted magnetic resonance imaging (MRI), on
      two occasions by two radiologists. Angle values and categorized pain scores were
      compared statistically between the groups. RESULTS: Intraobserver and
      interobserver agreement was over 97% for all measurements. Pain scores increased
      with decreasing CVA and CMA values. Mean angle values were significantly
      different among the pain categories (P < 0.001). The pain score was negatively
      correlated with CMA (Spearman correlation coefficient, rs, -0.676; P < 0.001) and
      CVA values (rs, -0.725; P < 0.001). CONCLUSION: CVA or CMA narrowing affects the
      occurrence of cervicogenic headache. There is an inverse relationship between the
      angle values and pain scores.

PMID- 24317333
TI  - Measurement of real-time tissue elastography in a phantom model and comparison
      with transient elastography in pediatric patients with liver diseases.
AB  - PURPOSE: We aimed to determine the comparability of real-time tissue elastography
      (RTE) and transient elastography (TE) in pediatric patients with liver diseases.
      MATERIALS AND METHODS: RTE was performed on the Elasticity QA Phantom Model 049
      (Computerized Imaging Reference Systems Company Inc., Norfolk, Virginia, USA),
      which has five areas with different levels of stiffness. RTE measurements of
      relative stiffness (MEAN [mean value of tissue elasticity], AREA [% of blue color
      coded stiffer tissue]) in the phantom were compared with the phantom stiffness
      specified in kPa (measurement unit of TE). RTE and TE were performed on 147
      pediatric patients with various liver diseases. A total of 109 measurements were
      valid. The participants had following diseases: metabolic liver disease (n=25),
      cystic fibrosis (n=20), hepatopathy of unknown origin (n=11), autoimmune
      hepatitis (n=12), Wilson's disease (n=11), and various liver parenchyma
      alterations (n=30). Correlations between RTE and TE measurements in the patients
      were calculated. In addition, RTE was performed on a control group (n=30), and
      the RTE values between the patient and control groups were compared. RESULTS: The
      RTE parameters showed good correlation in the phantom model with phantom
      stiffness (MEAN/kPa, r=-0.97; AREA/kPa, r=0.98). However, the correlation of RTE
      and TE was weak in the patient group (MEAN/kPa, r=-0.23; AREA/kPa, r=0.24). A
      significant difference was observed between the patient and control groups (MEAN,
      P = 5.32 e-7; AREA, P = 1.62 e-6). CONCLUSION: In the phantom model, RTE was
      correlated with kPa, confirming the presumed comparability of the methods.
      However, there was no direct correlation between RTE and TE in patients with
      defined liver diseases under real clinical conditions.

PMID- 24317334
TI  - mRECIST criteria and contrast-enhanced US for the assessment of the response of
      hepatocellular carcinoma to transarterial chemoembolization.
AB  - PURPOSE: We aimed to evaluate the combination of the modified Response Evaluation
      Criteria In Solid Tumors (mRECIST) and contrast-enhanced ultrasonography (CEUS)
      as a tool for the assessment of hepatocellular carcinoma treated with
      transarterial chemoembolization. MATERIALS AND METHODS: Forty-seven
      hepatocellular carcinoma patients (80 target tumors suitable for mRECIST
      measurements) were studied. They were treated with scheduled transarterial
      chemoembolization with doxorubicin-eluting microspheres every 5-7 weeks. Imaging
      follow-up (performed one month after each transarterial chemoembolization)
      included a standard, contrast-enhanced modality (computed tomography [CT] in 12
      patients or magnetic resonance imaging [MRI] in 35 patients) and CEUS. The study
      focused on response evaluation after the third transarterial chemoembolization.
      CEUS required a bolus injection of an echo-enhancer and imaging with a dedicated,
      low mechanical index technique. The longest diameters of the enhancing target
      tumors were measured on the CEUS or CT/MRI, and mRECIST criteria were applied.
      Radiologic responses were correlated with overall survival and time to
      progression. RESULTS: The measurements of longest diameters of the enhancing
      target tumors were easily performed in all patients. According to mRECIST-CEUS
      and mRECIST-CT/MRI, complete response was recorded in five and six patients,
      partial response in 22 and 21 patients, stable disease in 16 and 14 patients, and
      progressive disease in four and six patients, respectively. There was a high
      degree of concordance between CEUS and CT/MRI (kappa coefficient=0.84, P <
      0.001). Responders (complete+partial response) according to mRECIST-CEUS had a
      significantly longer mean overall survival and time to progression compared to
      nonresponders (37.1 vs. 11.0 months, P < 0.001 and 24.6 vs. 10.9 months, P =
      0.007, respectively). CONCLUSION: The mRECIST-CEUS combination is feasible and
      has prognostic value in the assessment of hepatocellular carcinoma following
      transarterial chemoembolization.

PMID- 24317335
TI  - Ultrashort echo time MRI of pulmonary water content: assessment in a sponge
      phantom at 1.5 and 3.0 Tesla.
AB  - PURPOSE: We aimed to develop a predictive model for lung water content using
      ultrashort echo time (UTE) magnetic resonance imaging (MRI) and a sponge phantom.
      MATERIALS AND METHODS: Image quality was preliminarily optimized, and the signal
      to-noise ratio (SNR) of UTE was compared with that obtained from a three
      dimensional fast gradient echo (FGRE) sequence. Four predetermined volumes of
      water (3.5, 3.0, 2.5, and 2.0 mL) were soaked in cellulose foam sponges 1.8 cm3
      in size and were imaged with UTE-MRI at 1.5 and 3.0 Tesla (T). A multiple echo
      time experiment (range, 0.1-9.6 ms) was conducted, and the T2 signal decay curve
      was determined at each volume of water. A three-parameter equation was fitted to
      the measured signal, allowing for the calculation of proton density and T2*. The
      calculation error of proton density was determined as a function of echo time.
      The constants that allowed for the determination of unknown volumes of water from
      the measured proton density were calculated using linear regression. RESULTS: UTE
      MRI provided excellent image quality for the four phantoms and showed a higher
      SNR, compared to that of FGRE. Proton density decreased proportionally with the
      decreases in both lung water and field strength (from 3.5 to 2.0 mL; proton
      density range at 1.5 T, 30.5-17.3; at 3.0 T, 84.2-41.5). Minimum echo time less
      than 0.6 ms at 1.5 T and 1 ms at 3.0 T maintained calculation errors for proton
      density within the range of 0%-10%. The slopes of the lines for determining the
      unknown volumes of water with UTE-MRI were 0.12+/-0.003 at 1.5 T and 0.05+/-0.002
      at 3.0 T (P < 0.0001). CONCLUSION: In a sponge phantom imaged at 1.5 and 3.0 T,
      unknown volumes of water can be predicted with high accuracy using UTE-MRI.

PMID- 24317336
TI  - An innovative modification of the retrograde approach to angioplasty and
      recanalization of the superficial femoral artery.
AB  - Endovascular therapy has been performed for chronic limb ischemia since 1964,
      with intraluminal and subintimal angioplasty of the superficial femoral artery
      (SFA) gaining popularity in the last decade (1). SFA occlusions can be managed by
      retrograde contralateral or antegrade ipsilateral approaches (2, 3); when these
      approaches fail, some practitioners resort to using a re-entry device (4, 5). The
      retrograde popliteal approach was initially fraught with limitations and served
      as a backup option (1, 4, 6). However, refinements to this technique have made
      this an enticing option (2-7), and it has been advocated as a first-line
      treatment in select patients (3). We herein describe another modification of this
      method. 

PMID- 24317338
TI  - Factors involved in the cisplatin resistance of KCP-4 human epidermoid carcinoma
      cells.
AB  - KCP-4 is a cisplatin-resistant cell line established from human epidermoid
      carcinoma KB-3-1 cells. Although our previous study revealed that one of the
      mechanisms for cisplatin resistance in KCP-4 cells is the activation of NF
      kappaB, its high resistance is considered to be induced by multiple mechanisms.
      In the present study, we explored other factors involved in the development of
      cisplatin resistance in KCP-4 cells. Since it has been reported that an unknown
      efflux pump exports cisplatin from KCP-4 cells in an ATP-dependent manner, we
      examined 48 types of ATP-binding cassette proteins as candidate cisplatin efflux
      transporters. The mRNA expression levels of ABCA1, ABCA3, ABCA7 and ABCB10 in KCP
      4 cells were higher when compared to those in KB-3-1 cells. These expression
      levels in cisplatin-sensitive revertant KCP-4 cells (KCP-4R cells), were reduced
      in parallel with the sensitivity of these cells to cisplatin and their
      intracellular accumulation of cisplatin. Next, we investigated the occurrence of
      mutations in p53 in KCP-4 cells. We found a heterozygous missense mutation at
      codon 72 (p.Pro72Arg) in p53 of both KCP-4 and KB-3-1 cells, but the protein
      expression level of p53 in KCP-4 cells was higher when compared to that in KB-3
      1. These results suggest that ABCA1, ABCA3, ABCA7 and ABCB10 are candidate genes
      for the cisplatin efflux transporter that is involved in the cisplatin resistance
      of KCP-4 cells, and that the mutation at codon 72 of p53 may contribute to the
      development of cisplatin resistance.

PMID- 24317339
TI  - [Assessment of resectability of colorectal liver metastases and extended
      resection].
AB  - Most patients with colorectal liver metastases are treated within a multimodal
      therapy regime whereby liver resection is a key point in the curative treatment
      concept. The achievement of an R0 situation is of vital importance for long-term
      survival. Besides general operability and the assessment of comorbidities,
      resection depends on the quality of liver parenchyma (functional resectability)
      and the anatomical position of the tumor (oncological resectability). The
      improvement of operation techniques and perioperative medicine nowadays allow
      complex surgical procedures for metastasis surgery. This article presents the
      methods for the assessment of resectability and modern strategies of preoperative
      conditioning as well as approaches for extended liver resection. 

PMID- 24317337
TI  - Metagenomics and novel gene discovery: promise and potential for novel
      therapeutics.
AB  - Metagenomics provides a means of assessing the total genetic pool of all the
      microbes in a particular environment, in a culture-independent manner. It has
      revealed unprecedented diversity in microbial community composition, which is
      further reflected in the encoded functional diversity of the genomes, a large
      proportion of which consists of novel genes. Herein, we review both sequence
      based and functional metagenomic methods to uncover novel genes and outline some
      of the associated problems of each type of approach, as well as potential
      solutions. Furthermore, we discuss the potential for metagenomic biotherapeutic
      discovery, with a particular focus on the human gut microbiome and finally, we
      outline how the discovery of novel genes may be used to create bioengineered
      probiotics. 

PMID- 24317341
TI  - Large-scale linear nonparallel support vector machine solver.
AB  - Twin support vector machines (TWSVMs), as the representative nonparallel
      hyperplane classifiers, have shown the effectiveness over standard SVMs from some
      aspects. However, they still have some serious defects restricting their further
      study and real applications: (1) They have to compute and store the inverse
      matrices before training, it is intractable for many applications where data
      appear with a huge number of instances as well as features; (2) TWSVMs lost the
      sparseness by using a quadratic loss function making the proximal hyperplane
      close enough to the class itself. This paper proposes a Sparse Linear Nonparallel
      Support Vector Machine, termed as L1-NPSVM, to deal with large-scale data based
      on an efficient solver-dual coordinate descent (DCD) method. Both theoretical
      analysis and experiments indicate that our method is not only suitable for large
      scale problems, but also performs as good as TWSVMs and SVMs. 

PMID- 24317340
TI  - Structural features and mechanism of translocation of non-LTR retrotransposons in
      Candida albicans.
AB  - A number of abundant mobile genetic elements called retrotransposons reverse
      transcribe RNA to generate DNA for insertion into eukaryotic genomes. Non-long
      terminal repeat (non-LTR) retrotransposons represent a major class of
      retrotransposons, and transposons that move by target-primed reverse
      transcription lack LTRs characteristic of retroviruses and retroviral-like
      transposons. Yeast model systems in Candida albicans and Saccharomyces cerevisiae
      have been developed for the study of non-LTR retrotransposons. Non-LTR
      retrotransposons are divided into LINEs (long interspersed nuclear elements),
      SINEs (short interspersed nuclear elements), and SVA (SINE, VNTR, and Alu). LINE
      1 elements have been described in fungi, and several families called Zorro
      elements have been detected from C. albicans. They are all members of L1 clades.
      Through a mechanism named target-primed reverse transcription (TPRT), LINEs
      translocate the new copy into the target site to initiate DNA synthesis primed by
      the 3' OH of the broken strand. In this article, we describe some advances in the
      research on structural features and origin of non-LTR retrotransposons in C.
      albicans, and discuss mechanisms underlying their reverse transcription and
      integration of the donor copy into the target site. 

PMID- 24317342
TI  - Sociogeographic variation in the effects of heat and cold on daily mortality in
      Japan.
AB  - BACKGROUND: Ambient temperature affects mortality in susceptible populations, but
      regional differences in this association remain unclear in Japan. We conducted a
      time-series study to examine the variation in the effects of ambient temperature
      on daily mortality across Japan. METHODS: A total of 731 558 all-age non
      accidental deaths in 6 cities during 2002-2007 were analyzed. The association
      between daily mortality and ambient temperature was examined using distributed
      lag nonlinear models with Poisson distribution. City-specific estimates were
      combined using random-effects meta-analysis. Bivariate random-effects meta
      regressions were used to examine the moderating effect of city characteristics.
      RESULTS: The effect of heat generally persisted for 1 to 2 days. In warmer
      communities, the effect of cold weather lasted for approximately 1 week. The
      combined increases in mortality risk due to heat (99th vs 90th percentile of city
      specific temperature) and cold (first vs 10th percentile) were 2.21% (95% CI,
      1.38%-3.04%) and 3.47% (1.75%-5.21%), respectively. City-specific effects based
      on absolute temperature changes were more heterogeneous than estimates based on
      relative changes, which suggests some degree of acclimatization. Northern
      populations with a cool climate appeared acclimatized to low temperature but were
      still vulnerable to extreme cold weather. Population density, average income,
      cost of property rental, and number of nurses appeared to influence variation in
      heat effect across cities. CONCLUSIONS: We noted clear regional variation in
      temperature-related increases in mortality risk, which should be considered when
      planning preventive measures.

PMID- 24317343
TI  - Is a cutoff of 10% appropriate for the change-in-estimate criterion of confounder
      identification?
AB  - BACKGROUND: When using the change-in-estimate criterion, a cutoff of 10% is
      commonly used to identify confounders. However, the appropriateness of this
      cutoff has never been evaluated. This study investigated cutoffs required under
      different conditions. METHODS: Four simulations were performed to select cutoffs
      that achieved a significance level of 5% and a power of 80%, using linear
      regression and logistic regression. A total of 10 000 simulations were run to
      obtain the percentage differences of the 4 fitted regression coefficients (with
      and without adjustment). RESULTS: In linear regression, larger effect size,
      larger sample size, and lower standard deviation of the error term led to a lower
      cutoff point at a 5% significance level. In contrast, larger effect size and a
      lower exposure-confounder correlation led to a lower cutoff point at 80% power.
      In logistic regression, a lower odds ratio and larger sample size led to a lower
      cutoff point at a 5% significance level, while a lower odds ratio, larger sample
      size, and lower exposure-confounder correlation yielded a lower cutoff point at
      80% power. CONCLUSIONS: Cutoff points for the change-in-estimate criterion varied
      according to the effect size of the exposure-outcome relationship, sample size,
      standard deviation of the regression error, and exposure-confounder correlation.

PMID- 24317344
TI  - Linkage rate between data from health checks and health insurance claims in the
      Japan National Database.
AB  - BACKGROUND: Japan's National Database (NDB) includes data on health checks and
      health insurance claims, is linkable using hash functions, and is available for
      research use. However, the linkage rate between health check and health insurance
      claims data has not been investigated. METHODS: Linkage rate was evaluated by
      comparing observed medical and pharmaceutical charges among health check
      recipients in fiscal year (FY) 2009 (N = 21 588 883) with expected charges from
      the same population when record linkage was complete. Using the NDB, observed
      charges were estimated from the first published result of linking health check
      recipients in FY2009 and their health insurance claims in FY2010. Expected
      charges were estimated by combining 3 publicly available datasets, including data
      from the Medical Care Benefit Survey and an ad-hoc report by the Japan Health
      Insurance Association. RESULTS: Only 14.9% of expected charges were linked by the
      NDB. The linkage rate was higher for women than for men (18.2% vs 12.4%) and for
      elderly adults as compared with younger adults (>25% vs <10%). CONCLUSIONS: The
      linkage rate in the NDB was so low that any research linking health check and
      health insurance claims will not be reliable. Causes for the low linkage rate
      include differences between health check and health insurance claims data in name
      format (eg, insertion of a space between family and given names) and date of
      birth (Japanese vs Gregorian calendar). Investigation of the causes for the low
      linkage rate and measures for improvement are urgently needed.

PMID- 24317345
TI  - The role of cholecystokinin in the induction of aggressive behavior: a focus on
      the available experimental data (review).
AB  - Cholecystokinin (CCK) is a neuropeptide that is (among others) reportedly
      involved in the pathophysiology of psychiatric disorders. The excitatory role of
      CCK in negative affective emotions as well as in aversive reactions, antisocial
      behaviors and memories, has been indicated by numerous electrophysiological,
      neurochemical and behavioral methodologies on both animal models for anxiety and
      human studies. The current review article summarizes the existing experimental
      evidence with regards to the role of CCK in the induction of aggressive behavior,
      and: (a) synopsizes the anatomical circuits through which it could potentially
      mediate all types of aggressive behavior, as well as (b) highlights the potential
      use of these experimental evidence in the current research quest for the clinical
      treatment of mood and anxiety disorders. 

PMID- 24317346
TI  - Molecular basis of chronic stress-induced hippocampal lateral asymmetry in rats
      and impact on learning and memory.
AB  - Neurochemical lateralization has been demonstrated in the rat brain suggesting
      that such lateralization might contribute to behavior. Thus, the aim of the
      present study was to examine neurochemical asymmetry in the hippocampus,
      molecular basis of neurochemical lateralization and its impact on spatial
      learning and memory. Changes in noradrenaline content, tyrosine hydroxylase (TH)
      were studied in the right and left hippocampus of naive control and chronically
      isolated rats, by applying TaqMan RT-PCR and Western blot analysis. Hippocampal
      based spatial learning and memory were evaluated using the Barnes maze. In
      control rats an asymmetrical right-left distribution of noradrenaline content and
      gene expression of catecholamine synthesizing enzyme was found. Chronic
      psychosocial stress further emphasized asymmetry. Isolation stress reduced
      noradrenaline content only in the right hippocampus. No changes were observed in
      gene expression and protein levels of TH in the right hippocampus, whereas
      expression of catecholamine synthesizing enzyme was elevated in the left
      hippocampus. Reduced noradrenaline content in the right hippocampus did not cause
      impairment in spatial learning and memory. Our findings suggest that chronic
      psychosocial stress reduces noradrenaline stores in the right hippocampus which
      may be caused by molecular asymmetry, but it does not affect spatial learning and
      memory. 

PMID- 24317347
TI  - Effect of inescapable stress in rodent models of depression and posttraumatic
      stress disorder on CRH and vasopressin immunoreactivity in the hypothalamic
      paraventricular nucleus.
AB  - The present study was designed to reveal possible common and specific
      neuroendocrine mechanisms of depression and anxiety-like states in rodents.
      Animal models of depression and anxiety (in particular, posttraumatic stress
      disorder, PTSD) were applied including the learned helplessness and the stress
      restress paradigms, respectively. Immunocytochemical staining revealed that
      depressive- and anxiety-like states in animals were accompanied by the rise in
      corticotropin-releasing hormone (CRH) immunoreactivity in the parvocellular
      division of the hypothalamic paraventricular nucleus (PVN). Decrease in
      vasopressin-immunoreactivity in early period of depressive-like state development
      was followed by the normalization of vasopressin content in the hypothalamic PVN
      in delayed period. Increased CRH and vasopressin immunoreactivity in the
      magnocellular part of the PVN in delayed period of anxiety-like state development
      was detected only in the stress-restress paradigm. These results suggest that CRH
      hyperdrive in the parvocellular PVN appears to be a common neuroendocrine
      abnormality for depressive- and anxiety-like states in animals, while over
      expression of CRH and vasopressin in the magnocellular PVN represents a specific
      feature of anxiety/PTSD-like state.

PMID- 24317348
TI  - Influence of continuous or intermittent blood flow restriction on muscle
      activation during low-intensity multiple sets of resistance exercise.
AB  - Low-intensity resistance exercise with blood flow restriction (BFR) has been
      shown to induce a prominent increase in muscle activation in response to muscle
      fatigue. However, the magnitude of muscle fatigue between continuous (Con-BFR)
      and intermittent BFR (Int-BFR, BFR only during exercise) is currently unknown. We
      examined the effect of Con-BFR or Int-BFR on muscle activation during exercise.
      Unilateral arm curl exercise (20% of one-repetition maximum, four sets, 30 sec
      rest period between sets) was performed without (CON) or with Con-BFR or Int-BFR.
      During BFR conditions, the cuff was inflated to 160 mmHg on the proximal region
      of testing arm. Surface electromyography (EMG) was recorded from the biceps
      brachii muscle, and integrated EMG (iEMG) was analyzed. During the exercise, iEMG
      increased progressively in Con-BFR and Int-BFR and both conditions were greater
      (p < 0.05) than CON at the 3rd and 4th set. However, there were no differences (p
      > 0.05) in iEMG between Con-BFR and Int-BFR during exercise (~2.45 and ~2.40
      times, respectively). Thus, the magnitude of increase in muscle activation may be
      similar between Con-BFR and Int-BFR when BFR exercise was performed at a high
      level of cuff pressure intensity. 

PMID- 24317349
TI  - Investigation of apoptosis in a canine model of chronic heart failure induced by
      tachycardia.
AB  - Participation of apoptosis during the development of pacing-induced dilated
      cardiomyopathy is not fully understood. After 7 weeks rapid right ventricular
      pacing, gene expressions of Bax, Bcl-2 and Caspase-3 were measured by RTQ-PCR
      from interventricular septum biopsies that were taken weekly in 21 beagle dogs
      during the development of heart failure. We evaluated protein levels of these
      genes by Western blot and DNA fragmentation by TUNEL method from autopsy samples.
      Gene expression of Bax remained unchanged during the pacing period; Bcl-2 mRNA
      expression transiently decreased in moderate heart failure and their ratio (Bcl
      2/Bax) was not significantly altered. Caspase-3 gene expression increased in
      heart failure. Compared to the control group, expression of Bax and Bcl-2
      proteins and their ratio were increased in dogs only after 4 weeks of pacing. No
      band of activated Caspase was found in the normal nor in the paced myocardium. In
      the TUNEL assay there was no significant difference between numbers of apoptotic
      cells in any of the groups, although a few TUNEL-positive cells were detected in
      the paced groups. Our results are not in favour of apoptosis in the pathogenesis
      of heart failure in this model and may be it could be attributed to activation of
      other systems. 

PMID- 24317351
TI  - Thromboelastogram evaluation of the impact of hypercoagulability in trauma
      patients.
AB  - INTRODUCTION: Admission hypocoagulability has been associated with negative
      outcomes after trauma. The purpose of this study was to determine the impact of
      hypercoagulability after trauma on the need for blood product transfusion and
      mortality. METHODS: Injured patients meeting our level I trauma center's highest
      activation criteria had a thromboelastography (TEG) performed at admission, +1 h,
      +2 h, and +6 h using citrated blood. Hypercoagulability was defined as any TEG
      parameter in the hypercoagulable range, and hypocoagulability as any parameter in
      the hypocoagulable range. Patients were followed up prospectively throughout
      their hospital course. RESULTS: A total of 118 patients were enrolled: 26.3% (n =
      31) were hypercoagulable, 55.9% (n = 66) had a normal TEG profile, and 17.8% (n =
      21) were hypocoagulable. After adjusting for differences in demographics and
      clinical data, hypercoagulable patients were less likely to require un-cross
      matched blood (11.1% for hypercoagulable vs. 20.4% for normal vs. 45.7% for
      hypocoagulable, adjusted P = 0.004). Hypercoagulable patients required less total
      blood products, in particular, plasma at 6 h (0.1 [SD, 0.4] U for hypercoagulable
      vs. 0.7 [SD, 1.9] U for normal vs. 4.3 [SD, 6.3] U for hypocoagulable, adjusted P
      < 0.001) and 24 h (0.2 [SD, 0.6] U for hypercoagulable vs. 1.1 [SD, 2.9] U for
      normal vs. 8.2 [SD, 19.3] U for hypocoagulable, adjusted P < 0.001).
      Hypercoagulable patients had lower 24-h mortality (0.0% vs. 5.5% vs. 27.8%,
      adjusted P < 0.001) and 7-day mortality (0.0% vs. 5.5% vs. 36.1%, adjusted P <
      0.001). Bleeding-related deaths were less likely in the hypercoagulable group
      (0.0% vs. 1.8% vs. 25.0%, adjusted P < 0.001). CONCLUSIONS: Approximately a
      quarter of trauma patients presented in a hypercoagulable state. Hypercoagulable
      patients required less blood products, in particular plasma. They also had a
      lower 24-h and 7-day mortality and lower rates of bleeding-related deaths.
      Further evaluation of the mechanism responsible for the hypercoagulable state and
      its implications on outcome is warranted.

PMID- 24317350
TI  - Knockdown of RBBP7 unveils a requirement of histone deacetylation for CPC
      function in mouse oocytes.
AB  - During mouse oocyte maturation histones are deacetylated, and inhibiting this
      deacetylation leads to abnormal chromosome segregation and aneuploidy. RBBP7 is a
      component of several different complexes that contain histone deacetylases, and
      therefore could be implicated in histone deacetylation. We find that Rbbp7 is a
      dormant maternal mRNA that is recruited for translation during oocyte maturation
      to regulate the histone deacetylation. Importantly, we show that the maturation
      associated decrease of histone acetylation is required for localization and
      function of the chromosomal passenger complex (CPC) during oocyte meiotic
      maturation. This finding can explain the phenotypes of oocytes where Rbbp7 is
      depleted by an siRNA/morpholino cocktail including severe chromosome
      misalignment, improper kinetochore-microtubule attachments, impaired SAC
      function, cytokinesis defects, and increased incidence of aneuploidy at metaphase
      II (Met II). These results implicate RBBP7 as a novel regulator of histone
      deacetylation during oocyte maturation and provide evidence that such
      deacetylation is required for proper chromosome segregation by regulating
      localized CPC function. 

PMID- 24317352
TI  - Plasma first in the field for postinjury hemorrhagic shock.
AB  - Hemorrhage is the most preventable cause of death in civilian and military
      trauma, and despite tremendous advances in patient transport in the field,
      survival within the first hour has changed little over the past 40 years. The
      pathogenesis of trauma-induced coagulopathy is multifactorial, but most
      authorities believe there is an early depletion of clotting factors. While fresh
      frozen plasma delivered early in the emergency department has been shown to be
      beneficial, the rapid onset of trauma-induced coagulopathy suggests advancing
      this concept to the scene may improve patient outcome. The purpose of this report
      was to describe the rationale and design of a randomized trial to test the
      hypothesis that prehospital "plasma-first" resuscitation will benefit the
      critically injured patient. The rationale includes the possibility that plasma
      first resuscitation may be advantageous beyond direct effects on clotting
      capacity. The study design is based on a ground ambulance system that allows
      rapid prehospital thawing of frozen plasma. 

PMID- 24317353
TI  - Role of macrophages in bile acid-induced inflammatory response of fetal lung
      during maternal cholestasis.
AB  - Infant respiratory distress syndrome (iRDS) in babies born from women with
      intrahepatic cholestasis of pregnancy (ICP) has been associated with intrauterine
      exposure to high bile acid levels. Here, we have investigated the role of
      macrophages in hypercholanemia-induced changes in maternal and fetal lung.
      Obstructive cholestasis in pregnant rats (OCP) was maintained from day 14 of
      gestation to term. Gene expression was determined by RT-QPCR, Western blot, and
      immunofluorescence. The maternal-fetal bile acid pool was radiolabelled using
      [(3)H]-taurocholate. OCP resulted in increased bile acids in maternal and fetal
      organs, including lungs. This was accompanied by structural changes in lung
      tissue, more marked in fetuses (peribronchial edema, collapse of alveolar spaces
      and deposits of hyaline material in the alveolar lumen), and infiltration of lung
      tissue by inflammatory cells. The abundance of macrophages and neutrophils in
      bronchoalveolar lavage fluid (BALF) was also increased in OCP group.
      Phospholipase A2-IIA (PLA2), the key enzyme in surfactant degradation, was mainly
      immunodetected in macrophages, which also expressed the bile acid receptor TGR5.
      The overall expression of PLA2 was markedly enhanced in maternal and fetal lungs
      of OCP group and in control maternal BALF cells incubated with bile acids. In
      neonates born from OCP mothers, the enhanced expression of erythropoietin
      suggested the presence of hypoxia due to iRDS. In conclusion, these results
      indicate that the accumulation of bile acids due to maternal cholestasis triggers
      an inflammatory response in the maternal and fetal lungs together with enhanced
      macrophage-associated PLA2 expression, which may play an important role in iRDS
      development. KEY MESSAGES: Maternal cholestasis causes respiratory distress
      syndrome in rat neonates. Cholestasis in pregnant rats causes bile acid
      accumulation in the fetal lung. This induces lung macrophages infiltration and
      inflammatory response. Alveolar macrophages co-express phospholipase A2-IIA and
      TGR5, but not FXR. Bile acid accumulation stimulates phospholipase A2-IIA, but
      not TGR5, expression.

PMID- 24317355
TI  - [Waldenstrom macroglobulinemia].
AB  - Waldenstrom macroglobulinemia is a rare lymphoproliferative disease of B-cell
      origin.These tumorous B-cells produce monoclonal IgM type protein. Diagnosis is
      based on the detection of lymphoplasmacytic invasion of the bone marrow and serum
      electrophoresis. Clinical symptoms such as anemia, hyperviscosity and neuropathy
      are the commom consequences of bone marrow infiltration and serum monoclonal IgM
      protein. Former use of alkylating agents are replaced by purine analogues,
      rituximab and bortezomib. Additional clinical data have also accumulated
      regarding autologous and allogenous stem-cell transplantation. The authors
      present their own clinical experience and give a detailed review of current
      therapeutic approaches. Orv. Hetil., 154(50), 1970-1974. 

PMID- 24317354
TI  - Smoking cessation during pregnancy and postpartum: practice patterns among
      obstetrician-gynecologists.
AB  - OBJECTIVES: To assess current obstetrician-gynecologist (ob-gyn) practice
      patterns related to the management of and barriers to smoking cessation during
      pregnancy and postpartum. METHODS: A smoking cessation questionnaire was mailed
      to 1024 American College of Obstetricians and Gynecologists Fellows in 2012.
      chi(2) analyses were used to assess for categorical differences between groups,
      Pearson r was used to conduct correlational analysis, and analysis of variance
      was used to assess for mean differences between groups. RESULTS: The analyses
      included 252 practicing ob-gyns who see pregnant patients who returned a
      completed survey. Ob-gyns estimated that 23% of their patients smoke before
      pregnancy, 18% smoke during first trimester, 12% during second trimester, and 11%
      during third trimester. They approximated that 32% quit during pregnancy, but 50%
      return to smoking postpartum. A large majority of ob-gyns feel that it is
      important for pregnant and postpartum women to quit smoking, and report asking
      all pregnant patients about tobacco use at the initial prenatal visit. Fewer ob
      gyns follow-up on tobacco use at subsequent visits when the patient has admitted
      to use at a prior visit. The primary barrier to intervention was reported as time
      limitations, though other barriers were noted that may be addressable through the
      provision of additional training and resources offered to physicians.
      CONCLUSIONS: Compared with findings from a similar study conducted in 1998,
      physicians are less likely to adhere to the 5 As smoking cessation guideline at
      present. As we know that brief intervention is effective, it is imperative that
      we work toward addressing practice gaps and providing additional resources to
      address the important public health issue of smoking during pregnancy and
      postpartum.

PMID- 24317356
TI  - [Attendance of the fourth (2008-2009) screening round of the Hungarian organized,
      nationwide breast cancer screening program].
AB  - INTRODUCTION: Organised, nationwide screening for breast cancer with mammography
      in the age group between 45 and 65 years with 2 years screening interval started
      in Hungary in January 2002. AIM: The aim of this study is to analyze the
      attendance rate of nationwide breast screening programme for the 2008-2009 years.
      METHOD: The data derive from the database of the National Health Insurance Fund
      Administration. The ratio of women in the age group 45-65 years was calculated
      having either a screening mammography or a diagnostic mammography in the 4th
      screening round of the programme. RESULTS: In the years 2000-2001, 7.6% of the
      women had an opportunistic screening mammography while in 2008-2009 31.2% of the
      target population had screening mammography within the organized programme.
      During the same periods 20.2% (2000-2001) and 20.4% (2008-2009) of women had a
      diagnostic mammography. Thus the total (screening and diagnostic) coverage of
      mammography increased from 26.6% (2000-2001) to 50.1% (2008-2009). The attendance
      rate failed to change between 2002 and 2009. CONCLUSIONS: In order to decrease
      the mortality due to breast cancer, the attendance rate of mammography screening
      programme should be increased. Orv. Hetil., 154(50), 1975-1983.

PMID- 24317357
TI  - [The stiff-person syndrome: a brief review and report of two cases].
AB  - The stiff-person syndrome is a rare and progressive neuromuscular disease which
      appears to have an immunpathological basis. It is characterised by painful muscle
      spasms and stiffness in the proximal muscles, especially those attached to the
      axial skeleton. The precise pathophysiology is still unknown, but several
      antibodies have been shown to be present in patients and these antibodies are
      directed against proteins which play a role in the inhibitor synapse linked to
      gamma-amino-butyrate. In the first part of the article the authors present two
      cases. In the second part they present a comprehensive review of our current
      knowledge about this rare disease. Orv.Hetil., 154(50), 1984-1990. 

PMID- 24317358
TI  - [Sentinel lymph node biopsy in pregnancy-associated breast cancer].
AB  - The incidence of pregnancy-associated breast cancer is rising. Sentinel lymph
      node biopsy is the method of choice in clinically node negative cases as the
      indicated minimally invasive regional staging procedure. Some reports have linked
      radioisotope and blue dye required for lymphatic mapping to teratogenic effects,
      the idea of which has become a generalized statement and, until recently,
      contraindication for these agents was considered during pregnancy. Today, there
      are many published reports of successful interventions with low-dose 99mTc
      labeled human albumin nanocolloid, based on dosimetric modeling demonstrating a
      negligible radiation exposure of the fetus. These results contributed to the
      seemingly safe and successful use of sentinel lymph node biopsy during pregnancy,
      though generally it can not replace axillary lymphadenectomy in the absence of
      high-quality evidence. The possibility of sentinel lymph node biopsy should be
      offered to pregnancy-associated early breast cancer patients with clinically
      negative axilla, and patients should be involved in the decision making following
      extensive counselling. This paper presents the successful use of sentinel lymph
      node biopsy with low-dose tracer during two pregnancies (in the first and third
      trimesters) and, for the first time in Hungarian language, it offers a
      comprehensive literature review on this topic. Orv. Hetil., 154(50), 1991-1997. 

PMID- 24317360
TI  - [In memoriam Dr. Sandor Szekely (1913-1991)].

PMID- 24317359
TI  - [A rare form of adrenal Cushing's syndrome].
AB  - The authors present the case history of a 74-year-old male suffering from aortic
      coarctation. His endocrine evaluation was initiated because of severe
      hypokalemia. The diagnostic procedures revealed the presence of Cushing's
      syndrome caused by bilateral macronodular adrenal hyperplasia. Because of the
      high risk of surgical treatment due to his cardiac condition, the patient was
      treated with the steroid biosynthesis inhibitor ketoconazole, which resulted in a
      clinical and biochemical regression of hypercortisolism. After interventional
      treatment of the aortic coarctation the physical and cardiac condition of the
      patient showed a significant improvement, indicating that despite an old age,
      surgery offered a valuable tool for management of the disease. To the best
      knowledge of the authors, the coexistence of aortic coarctation and bilateral
      macronodular adrenal hyperplasia has not been previously reported. Orv. Hetil.,
      154(50), 1999-2002. 

PMID- 24317361
TI  - [75th anniversary of the death of Karel Capek, the Czech writer and creator of
      the term "robot"].

PMID- 24317362
TI  - Evolutionary history of mitogen-activated protein kinase (MAPK) genes in Lotus,
      Medicago, and Phaseolus.
AB  - Mitogen-Activated Protein Kinase (MAPK) genes encode proteins that mediate
      various signaling pathways associated with biotic and abiotic stress responses in
      eukaryotes. The MAPK genes form a 3-tier signal transduction cascade between
      cellular stimuli and physiological responses. Recent identification of soybean
      MAPKs and availability of genome sequences from other legume species allowed us
      to identify their MAPK genes. The main objectives of this study were to identify
      MAPKs in 3 legume species, Lotus japonicus, Medicago truncatula, and Phaseolus
      vulgaris, and to assess their phylogenetic relationships. We used approaches in
      comparative genomics for MAPK gene identification and named the newly identified
      genes following Arabidopsis MAPK nomenclature model. We identified 19, 18, and 15
      MAPKs and 7, 4, and 9 MAPKKs in the genome of Lotus japonicus, Medicago
      truncatula, and Phaseolus vulgaris, respectively. Within clade placement of MAPKs
      and MAPKKs in the 3 legume species were consistent with those in soybean and
      Arabidopsis. Among 5 clades of MAPKs, 4 founder clades were consistent to MAPKs
      of other plant species and orthologs of MAPK genes in the fifth clade-"Clade E"
      were consistent with those in soybean. Our results also indicated that some gene
      duplication events might have occurred prior to eudicot-monocot divergence.
      Highly diversified MAPKs in soybean relative to those in 3 other legume species
      are attributable to the polyploidization events in soybean. The identification of
      the MAPK genes in the legume species is important for the legume crop
      improvement; and evolutionary relationships and functional divergence of these
      gene members provide insights into plant genome evolution. 

PMID- 24317363
TI  - miR-200b suppresses cell proliferation, migration and enhances chemosensitivity
      in prostate cancer by regulating Bmi-1.
AB  - microRNAs (miRNAs) are a class of small non-coding RNAs that can post
      transcriptionally regulate gene expression and play critical roles in many
      important biological processes. The role of miRNAs in prostate cancer (PCa)
      development and pathogenesis remains largely unknown. In the present study, we
      showed that miR-200b was downregulated in clinical prostatic tumors when compared
      to normal prostate tissue and in advanced PCa cell lines when compared to normal
      epithelial prostatic cells. Enforced miR-200b expression suppressed PCa cell
      proliferation and migration and enhanced chemosensitivity to docetaxel by
      targeting B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1).
      Bmi-1 was detected at higher levels in PCa, and knockdown of Bmi-1 showed similar
      effects as miR-200b overexpression in PCa cells. Moreover, we confirmed that
      these effects were correlated with increased levels of E-cadherin and P16 and a
      reduction in vimentin expression and expression of stem cell markers (CD44 and
      OCT4). These findings suggest that miR-200b plays vital roles as a tumor
      suppressor by targeting Bmi-1 and may be a promising therapeutic target for PCa
      treatment.

PMID- 24317364
TI  - Measurement of spatiotemporal intracellular deformation of cells adhered to
      collagen matrix during freezing of biomaterials.
AB  - Preservation of structural integrity inside cells and at cell-extracellular
      matrix (ECM) interfaces is a key challenge during freezing of biomaterials. Since
      the post-thaw functionality of cells depends on the extent of change in the
      cytoskeletal structure caused by complex cell-ECM adhesion, spatiotemporal
      deformation inside the cell was measured using a newly developed microbead
      mediated particle tracking deformetry (PTD) technique using fibroblast-seeded
      dermal equivalents as a model tissue. Fibronectin-coated 500 nm diameter
      microbeads were internalized in cells, and the microbead-labeled cells were used
      to prepare engineered tissue with type I collagen matrices. After a 24 h
      incubation the engineered tissues were directionally frozen, and the cells were
      imaged during the process. The microbeads were tracked, and spatiotemporal
      deformation inside the cells was computed from the tracking data using the PTD
      method. Effects of particle size on the deformation measurement method were
      tested, and it was found that microbeads represent cell deformation to acceptable
      accuracy. The results showed complex spatiotemporal deformation patterns in the
      cells. Large deformation in the cells and detachments of cells from the ECM were
      observed. At the cellular scale, variable directionality of the deformation was
      found in contrast to the one-dimensional deformation pattern observed at the
      tissue scale, as found from earlier studies. In summary, this method can quantify
      the spatiotemporal deformation in cells and can be correlated to the freezing
      induced change in the structure of cytosplasm and of the cell-ECM interface. As a
      broader application, this method may be used to compute deformation of cells in
      the ECM environment for physiological processes, namely cell migration, stem cell
      differentiation, vasculogenesis, and cancer metastasis, which have relevance to
      quantify mechanotransduction. 

PMID- 24317365
TI  - Molecularly imprinted fibers with renewable surface for solid-phase
      microextraction of triazoles from grape juice samples followed by gas
      chromatography mass spectrometry analysis.
AB  - This paper describes the synthesis and characterization of a new molecularly
      imprinted solid-phase microextraction fiber able to renew its selective binding
      sites because of the gradual thermal decomposition of the polymeric network. The
      injector of the chromatograph operates at 300  degrees C, and during the
      desorption step of the analytes (in a short period), the polymeric network is
      degraded from the surface to the core in volatile compounds that do not interfere
      with the analysis. The renewable MIP fiber was successfully employed to extract
      triazole fungicides (triadimenol, tebuconazole, and metconazole) from grape juice
      samples followed by gas chromatography mass spectrometry analysis. The method was
      adjusted to the quadratic models from 100 to 2000 MUg L(-1), with good precision
      and accuracy. The limits of quantification (100 MUg L(-1) for all analytes) were
      sufficient to analyze triadimenol, tebuconazole, and metconazole in grape juice
      samples, where their maximum residue limits in Brazil are 100, 2000, and 1000 MUg
      L(-1), respectively. 

PMID- 24317367
TI  - Inheritance of bud-set and bud-flushing in Picea abies (L.) Karst.
AB  - Diallel crosses were made between clones of a French and a Swedish provenance of
      Picea abies. The former is characterized by a long critical night length for bud
      set and a late flushing of the buds; the latter by a short critical night length
      for bud-set and an early flushing of the buds. The F1 hybrid seedlings and their
      French and Swedish intraprovenance half-sibs were tested over three growth
      periods in the phytotron at the College of Forestry, Stockholm. In comparison
      with intraprovenance half-sibs, the hybrid progenies gave, on average, an
      intermediate response for the photoperiodic control over budset and for the
      temperature requirements for bud-flushing. This indicates the prevalence of
      additive action of multiple factors in the determination of the photoperiodic and
      temperature response. However, individual interprovenance hybrid progenies
      revealed a range of responses, and in certain combinations the response of these
      hybrids and their intraprovenance half-sibs coincided. By selection of suitable
      parents, interprovenance crosses can be used to produce hybrids with desired
      photoperiodic characteristics and temperature requirements. 

PMID- 24317366
TI  - Short-term supplementation with a specific combination of dietary polyphenols
      increases energy expenditure and alters substrate metabolism in overweight
      subjects.
AB  - BACKGROUND AND OBJECTIVES: Impaired regulation of lipid oxidation (metabolic
      inflexibility) is associated with obesity and type 2 diabetes mellitus. Recent
      evidence has indicated that dietary polyphenols may modulate mitochondrial
      function, substrate metabolism and energy expenditure in humans. The present
      study investigated the effects of short-term supplementation of two combinations
      of polyphenols on energy expenditure (EE) and substrate metabolism in overweight
      subjects. SUBJECTS AND METHODS: Eighteen healthy overweight volunteers (9 women,
      9 men; age 35+/-2.5 years; body mass index 28.9+/-0.4 kg m(-2)) participated in a
      randomized, double-blind cross-over trial. Combinations of epigallocatechin
      gallate (E, 282 mg day(-1))+resveratrol (R, 200 mg day(-1)) and E+R+80 mg day(-1)
      soy isoflavones (S) or placebo capsules (PLA) were supplemented twice daily for a
      period of 3 days. On day 3, circulating metabolite concentrations, EE and
      substrate oxidation (using indirect calorimetry) were measured during fasting and
      postprandial conditions for 6 h (high-fat-mixed meal (2.6 MJ, 61.2 E% fat)).
      RESULTS: Short-term supplementation of E+R increased resting EE (E+R vs PLA:
      5.45+/-0.24 vs 5.23+/-0.25 kJ min(-1), P=0.039), whereas both E+R (699+/-18 kJ
      120 min(-1) vs 676+/-20 kJ 120 min(-1), P=0.028) and E+R+S (704+/-18 kJ 120 min(
      1) vs 676+/-20 kJ 120 min(-1), P=0.014) increased 2-4 h-postprandial EE compared
      with PLA. Metabolic flexibility, calculated as the postprandial increase to the
      highest respiratory quotient achieved, tended to be improved by E+R compared with
      PLA and E+R+S only in men (E+R vs PLA: 0.11+/-0.02 vs 0.06+/-0.02, P=0.059;
      E+R+S: 0.03+/-0.02, P=0.009). E+R+S significantly increased fasting plasma free
      fatty acid (P=0.064) and glycerol (P=0.021) concentrations compared with PLA.
      CONCLUSIONS: We demonstrated for the first time that combined E+R supplementation
      for 3 days significantly increased fasting and postprandial EE, which was
      accompanied by improved metabolic flexibility in men but not in women. Addition
      of soy isoflavones partially reversed these effects possibly due to their higher
      lipolytic potential. The present findings may imply that long-term
      supplementation of these dosages of epigallocatechin-gallate combined with
      resveratrol may improve metabolic health and body weight regulation.

PMID- 24317368
TI  - A population genetic analysis of self- and cross-incompatibility in sugar beet
      (Beta Vulgaris L.).
AB  - A population genetic model is proposed for the reproduction of self-incompatible
      inbred lines in which incompatibility is controlled by 1-4 loci. From theoretical
      considerations it was expected that: a) with the random matings of lines In,
      (obtained by self-pollination of n generations), some lines would be cross
      incompatible (all the plants within these lines would be homozygous for S-genes)
      and the rest would be cross-compatible (retain heterozygosity for one or more S
      genes); b) in the case of random matings of Unes InGm (obtained by self
      pollination of n generations and by random pollination for m generations), some
      lines would be cross-incompatible (heterozygous for one S-gene) and the rest
      would be cross-compatible (retain heterozygosity for two or more S-genes); c) the
      relative proportion of sterile plants, obtained by random pollination of cross
      compatible lines, would be related to the number of segregating S-loci and to the
      generation in which the lines are studied.Forty-four inbred lines of sugar beet
      derived from self-incompatible plants of a population were analysed. Comparisons
      of the observed values with the theoretically expected ones demonstrated that: a)
      of 18 In (I1-I4) lines, 6 were cross-incompatible (homozygous for S-genes) and 12
      were cross-compatible having one S-locus segregating in 7 lines and two S-loci
      segregating in 5 lines; b) of 22 InG1 (I2G1 and I3G1) lines, one line was self
      fertile, 7 lines were cross-incompatible (heterozygous for one S-loci) and 14
      lines were cross-compatible (heterozygous for two S-loci).No line was found to
      have three or more segregating S-loci. The results of this population genetics
      analysis of self- and cross-incompatibility in sugar beet comply with diallel
      analysis data on sugar beet incompatibility and indicates that it is under the
      gametophytic control of two basic S-loci. 

PMID- 24317369
TI  - Evaluation of circulant partial diallel crosses in maize.
AB  - The present study was conducted in maize (Zea mays L.) on crosses among 20
      diverse parents. The materials were evaluated in four different environments for
      eight characters. Combining ability analysis was carried out following diallel
      and partial diallel crosses. The number of crosses per parent (s) varied from 3
      to 19 and the results were studied to identify the critical value of s that would
      provide an adequate information with minimum resources. The S5 partial diallel
      was as good as the S19 for the detection of differences among general combining
      ability (GCA) effects. Even the S3 gave adequate information in the case of
      characters with high heritability. However, partial diallel analysis was less
      efficient in detecting the differences due to specific combining ability (SCA)
      effects. These results varied with environments, and characters with low
      heritability were more prone to misinterpretation. GCA effects showed
      fluctuations in partial diallel analysis which were more pronounced in S5 and S3,
      particularly for characters with low heritability. The average standard error of
      difference between GCA effects increased with a decrease in s, with a steep slope
      for s < 7. The partial diallel analysis was more efficient for the estimation of
      the variance component of GCA than for SCA, as the estimate of SCA was biased
      upwards. Estimates of broad sense heritability obtained from the partial diallels
      agreed with the full diallel analysis better than the narrow sense estimates.
      Smaller partial diallels gave erratic estimates of heritability, particularly for
      the characters with low heritability. 

PMID- 24317370
TI  - Univariate and multivariate analysis on phenotypic divergence in Phleum.
AB  - An analysis of phenotypic and genetic variability was performed on Phleum
      ambiguum populations obtained by vegetative propagation and grown in different
      environments. The investigation on a single character and the canonical analysis
      on several plant traits indicate that, while genetic variability (h(2)) is
      essentially constant, phenotypic variance and covariance are affected by
      different environments and successive clonations. The observed changes seem not
      to be reversible when plants, transferred to a different environment, are
      returned to the original one. Within-clones variability seems to be affected by
      environmental conditions without being directly related to them. The results
      reported seem to be in good agreement with the phenotypic divergence hypothesis. 

PMID- 24317371
TI  - Development of an open metadata schema for prospective clinical research
      (openPCR) in China.
AB  - OBJECTIVES: In China, deployment of electronic data capture (EDC) and clinical
      data management system (CDMS) for clinical research (CR) is in its very early
      stage, and about 90% of clinical studies collected and submitted clinical data
      manually. This work aims to build an open metadata schema for Prospective
      Clinical Research (openPCR) in China based on openEHR archetypes, in order to
      help Chinese researchers easily create specific data entry templates for
      registration, study design and clinical data collection. METHODS: Singapore
      Framework for Dublin Core Application Profiles (DCAP) is used to develop openPCR
      and four steps such as defining the core functional requirements and deducing the
      core metadata items, developing archetype models, defining metadata terms and
      creating archetype records, and finally developing implementation syntax are
      followed. RESULTS: The core functional requirements are divided into three
      categories: requirements for research registration, requirements for trial
      design, and requirements for case report form (CRF). 74 metadata items are
      identified and their Chinese authority names are created. The minimum metadata
      set of openPCR includes 3 documents, 6 sections, 26 top level data groups, 32
      lower data groups and 74 data elements. The top level container in openPCR is
      composed of public document, internal document and clinical document archetypes.
      A hierarchical structure of openPCR is established according to Data Structure of
      Electronic Health Record Architecture and Data Standard of China (Chinese EHR
      Standard). Metadata attributes are grouped into six parts: identification,
      definition, representation, relation, usage guides, and administration.
      DISCUSSIONS AND CONCLUSION: OpenPCR is an open metadata schema based on research
      registration standards, standards of the Clinical Data Interchange Standards
      Consortium (CDISC) and Chinese healthcare related standards, and is to be
      publicly available throughout China. It considers future integration of EHR and
      CR by adopting data structure and data terms in Chinese EHR Standard. Archetypes
      in openPCR are modularity models and can be separated, recombined, and reused.
      The authors recommend that the method to develop openPCR can be referenced by
      other countries when designing metadata schema of clinical research. In the next
      steps, openPCR should be used in a number of CR projects to test its
      applicability and to continuously improve its coverage. Besides, metadata schema
      for research protocol can be developed to structurize and standardize protocol,
      and syntactical interoperability of openPCR with other related standards can be
      considered.

PMID- 24317372
TI  - The relationship between motor development, gestures and language production in
      the second year of life: a mediational analysis.
AB  - This longitudinal study investigated the relationships between motor, gestural
      and linguistic abilities using two parent report instruments. Motor skills at 12
      months significantly correlated with language production at 16, 20 and 23 months,
      but these associations were mediated by the use of representational gestures. 

PMID- 24317373
TI  - Tolerance of geometric distortions in infant's face recognition.
AB  - The aim of the current study is to reveal the effect of global linear
      transformations (shearing, horizontal stretching, and vertical stretching) on the
      recognition of familiar faces (e.g., a mother's face) in 6- to 7-month-old
      infants. In this experiment, we applied the global linear transformations to both
      the infants' own mother's face and to a stranger's face, and we tested infants'
      preference between these faces. We found that only 7-month-old infants maintained
      preference for their own mother's face during the presentation of vertical
      stretching, while the preference for the mother's face disappeared during the
      presentation of shearing or horizontal stretching. These findings suggest that 7
      month-old infants might not recognize faces based on calculating the absolute
      distance between facial features, and that the vertical dimension of facial
      features might be more related to infants' face recognition rather than the
      horizontal dimension. 

PMID- 24317374
TI  - Light-triggered reversible sorption of azo dyes on titanium xerogels with photo
      switchable acetylacetonato anchors.
AB  - Photo-induced reversible sorption of azo dyes on titania xerogels is observed,
      which is based on the photo-switchable change of the acetylacetonato anchors in
      the xerogels. The photoisomerization of azo compounds that regulates many gate
      keeper-like host-guest interaction systems is excluded as the determinant. 

PMID- 24317375
TI  - Attenuated insular processing during risk predicts relapse in early abstinent
      methamphetamine-dependent individuals.
AB  - There is some evidence that neuroimaging can be used to predict relapse among
      abstinent methamphetamine-dependent (MD) individuals. However, it remains unclear
      what cognitive and neural processes contribute to relapse. This investigation
      examined whether insula activation during risk-taking decisions-a process shown
      to be disrupted in MD-is able to predict susceptibility for relapse. Sixty-eight
      MD enrolled in a treatment program during early abstinence completed a risk
      taking task during functional magnetic resonance imaging. Sixty-three of the
      sixty-eight individuals were followed up 1 year after the study. Of these, 18 MD
      reported relapse. The 45 abstinent MD showed patterns of insula activation during
      risky decisions that resembled those found in prior studies of healthy controls,
      consisting of lower insula activation during safe decisions paired with higher
      activation during risky decisions. In contrast, the 18 relapsed MD showed similar
      insula activation during safe and risky decisions. An increase in one standard
      deviation in the difference in insula activation between risky and safe choices
      was associated with a 0.34 odds ratio for relapse at any given time. A median
      split of insula activation (difference between risky and safe) showed that
      individuals in the bottom half were two times more likely to relapse. In
      addition, a model that included several other brain regions increased prediction
      accuracy compared with insula-based model alone. These results suggest that
      failure to differentially activate the insula as a function of risk is a part of
      an altered risk-processing network associated with an increased susceptibility to
      relapse. 

PMID- 24317376
TI  - Intrahepatic microcirculatory disorder, parenchymal hypoxia and NOX4 upregulation
      result in zonal differences in hepatocyte apoptosis following lipopolysaccharide-
      and D-galactosamine-induced acute liver failure in rats.
AB  - Although the mechanisms responsible for acute liver failure (ALF) have not yet
      been fully elucidated, studies have indicated that intrahepatic macrophage
      activation plays an important role in the pathogenesis of ALF through
      intrahepatic microcirculatory disorder and consequent parenchymal cell death.
      Intrahepatic microcirculatory disorder has been demonstrated in animal models
      using intravital microscopy; however, the limitations of this method include
      simultaneously evaluating blood flow and the surrounding pathological changes.
      Therefore, in this study, we devised a novel method involving
      tetramethylrhodamine isothiocyanate (TRITC)-dextran administration for the
      pathological assessment of hepatic microcirculation. In addition, we aimed to
      elucidate the mechanisms through which intrahepatic microcirculatory disorder
      progresses with relation to activated macrophages. ALF was induced in Wistar rats
      by exposure to lipopolysaccharide and D-galactosamine. Intrahepatic
      microcirculation and microcirculatory disorder in zone 3 (pericentral zone) of
      the livers of rats with ALF was observed. Immunohistochemical examinations in
      conjunction with TRITC-dextran images revealed that the macrophages were mainly
      distributed in zone 2 (intermediate zone), while cleaved caspase-3-positive
      hepatocytes, pimonidazole and hypoxia-inducible factor 1-alpha were abundant in
      zone 3. We also found that 4-hydroxy-2-nonenal and nicotinamide adenine
      dinucleotide phosphate oxidase (NOX)4-positive cells were predominantly located
      in the zone 3 parenchyma. The majority of apoptotic hepatocytes in zone 3 were co
      localized with NOX4. Our results revealed that the apoptotic cells in zone 3 were
      a result of hypoxic conditions induced by intrahepatic microcirculatory disorder,
      and were not induced by activated macrophages. The increased levels of oxidative
      stress in zone 3 may contribute to the progression of hepatocyte apoptosis.

PMID- 24317378
TI  - Falls are associated with stroke, arthritis and multiple medications among
      community-dwelling elderly persons in Japan.
AB  - Falls are a major public health problem and the second leading cause of death due
      to unintentional accidental injury after road traffic accidents. Inactive, older
      individuals with several chronic illnesses fall more frequently than older
      individuals who are active and healthy. No population-based study has addressed
      the association of stroke, arthritis, hypnotic and other prescription medications
      with falls among the elderly simultaneously in a single population in Japan. We
      examined the prevalence of falls among community-dwelling elderly Japanese
      individuals, whom we randomly selected from a list of inhabitants aged >= 65
      years compiled from the resident registration, and the associations between falls
      and each of stroke, arthritis, and hypnotic and other prescription medications.
      We interviewed 295 men and 307 women, and collected information about the number
      of falls during the latest one year, hemiplegia due to stroke, arthritis in the
      legs, and the number of hypnotic and other medications. We found that 46 men
      (16%) and 67 women (22%) had fallen at least once during the latest one year.
      Logistic regression analysis adjusted for age showed that hemiplegia due to
      stroke (p < 0.001), arthritis in the legs (p < 0.001), and taking at least four
      daily prescription medications (p < 0.05) were significantly associated with
      falls in men. Arthritis in the legs (p = 0.05) and taking at least four daily
      prescription medications (p < 0.05) were associated with falls in women.
      Treatment of fall-related diseases and medication management are important
      strategies for reducing falls among elderly persons. 

PMID- 24317380
TI  - Recruiting hard-to-reach subjects for exercise interventions: a multi-centre and
      multi-stage approach targeting general practitioners and their community-dwelling
      and mobility-limited patients.
AB  - The general practitioner (GP)'s practice appears to be an ideal venue for
      recruiting community-dwelling older adults with limited mobility. This study
      (Current Controlled Trials ISRCTN17727272) aimed at evaluating the recruiting
      process used for a multi-centre exercise intervention (HOMEfit). Each of six
      steps resulted in an absolute number of patients (N1-N6). Sex and age (for N4-N6)
      and reasons for dropping out were assessed. Patient database screening (N1-N3) at
      15 GP practices yielded N1 = 5,990 patients aged 70 and above who had visited
      their GP within the past 6 months, N2 = 5,467 after exclusion of
      institutionalised patients, N3 = 1,545 patients eligible. Using a pre-defined
      limitation algorithm in order to conserve the practices' resources resulted in N4
      = 1,214 patients (80.3 +/- 5.6 years, 68% female), who were then officially
      invited to the final assessment of eligibility at the GP's practice. N5 = 434
      patients (79.5 +/- 5.4 years, 69% female) attended the practice screening (n = 13
      of whom had not received an official invitation). Finally, N6 = 209 (79.8 +/- 5.2
      years, 74% female) were randomised after they were judged eligible and had given
      their written informed consent to participate in the randomised controlled trial
      (overall recruitment rate: 4.4%). The general strategy of utilising a GP's
      practice to recruit the target group proved beneficial. The data and experiences
      presented here can help planners of future exercise-intervention studies. 

PMID- 24317381
TI  - Indicators for healthy ageing--a debate.
AB  - Definitions of healthy ageing include survival to a specific age, being free of
      chronic diseases, autonomy in activities of daily living, wellbeing, good quality
      of life, high social participation, only mild cognitive or functional impairment,
      and little or no disability. The working group Epidemiology of Ageing of the
      German Association of Epidemiology organized a workshop in 2012 with the aim to
      present different indicators used in German studies and to discuss their impact
      on health for an ageing middle-European population. Workshop presentations
      focused on prevalence of chronic diseases and multimorbidity, development of
      healthy life expectancy at the transition to oldest-age, physical activity,
      assessment of cognitive capability, and functioning and disability in old age.
      The communication describes the results regarding specific indicators for
      Germany, and hereby contributes to the further development of a set of indicators
      for the assessment of healthy ageing. 

PMID- 24317382
TI  - Prevalence of sedentary behavior in older adults: a systematic review.
AB  - Sedentary behavior is a cluster of behaviors adopted in a sitting or lying
      posture where little energy is being expended. Sedentary behavior is a risk
      factor for health independent to inactivity. Currently, there are no published
      systematic reviews on the prevalence of sedentary behavior objectively measured
      in, or subjectively reported by, older adults. The aim of this systematic review
      was to collect and analyze published literature relating to reported prevalence
      of sedentary behavior, written in English, on human adults, where subjects aged
      60 years and over were represented in the study. 23 reports covered data from 18
      surveys sourced from seven countries. It was noted that sedentary behavior is
      defined in different ways by each survey. The majority of surveys included used
      self-report as a measurement of sedentary behavior. Objective measurements were
      also captured with the use of body worn accelerometers. Whether measurements are
      subjective or objective, the majority of older adults are sedentary. Almost 60%
      of older adult's reported sitting for more than 4 h per day, 65% sit in front of
      a screen for more than 3 h daily and over 55% report watching more than 2 h of
      TV. However, when measured objectively in a small survey, it was found that 67%
      of the older population were sedentary for more than 8.5 h daily. 

PMID- 24317383
TI  - Associations of job stress indicators with oxidative biomarkers in Japanese men
      and women.
AB  - Some researchers have suggested that oxidative damage may be one of the
      mechanisms linking job stress with coronary heart disease. The aim of this study
      was to investigate the association between job stress indicators and oxidative
      biomarkers. The study included 567 subjects (272 men, 295 women) who answered
      questionnaires related to their work and underwent a medical examination. Job
      stress evaluated using the demands-control-support model was measured using the
      Job Content Questionnaire. Effort-reward imbalance was measured using the Effort
      Reward Imbalance Questionnaire. Urinary hydrogen peroxide (H2O2) and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) were measured by the modified ferrous ion oxidation
      xylenol orange version-1 method and enzyme-linked immunosorbent assay,
      respectively. In men, the changes in the odds ratios for high urinary H2O2
      associated with a 1-standard-deviation (SD) increase in worksite social support
      were 0.69 (95% confidence interval (CI) 0.53, 0.91) univariately and 0.68 (95%CI
      0.51, 0.90) after adjustment for covariates. The change in the odds ratio for
      high urinary H2O2 associated with a 1-SD increase in effort-reward ratio was 1.35
      (95% CI 1.03, 1.78) after adjustment for covariates. In women, there were no
      significant associations of the two job stress indicators with urinary H2O2 and 8
      OHdG levels after adjustment for covariates (p > 0.05). 

PMID- 24317384
TI  - Physical performance and quality of life of nursing-home residents with mild and
      moderate dementia.
AB  - INTRODUCTION: The aims of this study were to describe the quality of life (QoL)
      of nursing-home residents with dementia and their balance, mobility, muscle
      strength and daily life activity, as well as to examine the associations between
      QoL and levels of balance, mobility, muscle strength and daily life activity.
      METHODS: The study is cross sectional, and 170 nursing-home residents with
      dementia were included. TESTS: "The quality of life in late-stage dementia scale"
      (QUALID), Berg Balance Scale, comfortable walking speed, maximum walking speed,
      30-s sit-to-stand, Barthel Index, Clinical Dementia Rating Scale, the Clock
      Drawing Test and the Mini-Mental State Examination (MMSE) were used. RESULTS: Our
      study showed that nursing-home residents with dementia are a heterogeneous group
      regarding registrations of QUALID and physical function measures. The scores on
      the QUALID ranged from 11 to 41 points. Higher scores on the 30-s sit-to-stand
      and Berg Balance Scale were associated with a better QUALID. For comfortable, as
      well as maximum, walking speed there was a trend towards better QUALID results
      for those participants with higher walking speed. CONCLUSIONS: Good muscle
      strength and balance were the most important physical performance variables
      significantly associated with a good QUALID score.

PMID- 24317379
TI  - West Nile virus state of the art report of MALWEST Project.
AB  - During the last three years Greece is experiencing the emergence of West Nile
      virus (WNV) epidemics. Within this framework, an integrated surveillance and
      control programme (MALWEST project) with thirteen associate partners was launched
      aiming to investigate the disease and suggest appropriate interventions. One out
      of seven work packages of the project is dedicated to the State of the Art report
      for WNV. Three expert working groups on humans, animals and mosquitoes were
      established. Medical databases (PubMed, Scopus) were searched together with
      websites: e.g., WHO, CDC, ECDC. In total, 1,092 relevant articles were initially
      identified and 258 of them were finally included as references regarding the
      current knowledge about WNV, along with 36 additional sources (conference papers,
      reports, book chapters). The review is divided in three sections according to the
      fields of interest: (1) WNV in humans (epidemiology, molecular characteristics,
      transmission, diagnosis, treatment, prevention, surveillance); (2) WNV in animals
      (epidemiological and transmission characteristics concerning birds, horses,
      reptiles and other animal species) and (3) WNV in mosquitoes (control,
      surveillance). Finally, some examples of integrated surveillance programmes are
      presented. The introduction and establishment of the disease in Greece and other
      European countries further emphasizes the need for thorough research and
      broadening of our knowledge on this viral pathogen. 

PMID- 24317385
TI  - Lead ions encapsulated in liposomes and their effect on Staphylococcus aureus.
AB  - The aim of the study was the preparation of a liposome complex with encapsulated
      lead ions, which were electrochemically detected. In particular, experiments were
      focused on the potential of using an electrochemical method for the determination
      of free and liposome-encapsulated lead and determination of the encapsulation
      efficiency preventing the lead toxicity. Primarily, encapsulation of lead ions in
      liposomes and confirmation of successful encapsulation by electrochemical methods
      was done. Further, the reduction effect of the liposome matrix on the detected
      electrochemical signal was monitored. Besides encapsulation itself, comparison of
      toxicity of free lead ions and lead ions encapsulated in liposome was tested. The
      calculated IC50 values for evaluating the lead cytotoxicity showed significant
      differences between the lead enclosed in liposomes (28 uM) and free lead ions
      (237 uM). From the cytotoxicity studies on the bacterial strain of S. aureus it
      was observed that the free lead ions are less toxic in comparison with lead
      encapsulated in liposomes. Liposomes appear to be a suitable carrier of various
      substances through the inner cavity. Due to the liposome structure the lead
      enclosed in the liposome is more easily accepted into the cell structure and the
      toxicity of the enclosed lead is higher in comparison to free lead ions. 

PMID- 24317386
TI  - Analysis of newspaper coverage of active aging through the lens of the 2002 World
      Health Organization Active Ageing Report: A Policy Framework and the 2010 Toronto
      Charter for Physical Activity: A Global Call for Action.
AB  - As populations continue to grow older, efforts to support the process of aging
      well are important goals. Various synonyms are used to cover aging well, such as
      active aging. The World Health Organization published in 2002 the report Active
      Ageing: A Policy Framework that according to the call for papers, has brought
      active ageing to the forefront of international public health awareness. The 2010
      Toronto Charter for Physical Activity: A Global Call for Action was singled out
      in the call for papers as a key document promoting physical activity one goal of
      the 2002 WHO active aging policy framework. Media are to report to the public
      topics of importance to them. We investigated the newspaper coverage of aging
      well and synonymous terms such as active aging through the lens of the 2002 WHO
      active aging policy framework and the 2010 Toronto Charter for Physical Activity.
      As sources we used the following newspapers: China Daily, The Star (Malaysia),
      two UK newspapers (The Guardian, The Times), a database of 300 Canadian
      newspapers (Canadian Newsstand) and a US newspaper (The New York Times). The
      study generated data answering the following four research questions: (1) how
      often are the 2002 WHO active aging policy framework and the 2010 Toronto Charter
      for Physical Activity mentioned; (2) how often is the topic of active aging and
      terms conveying similar content (aging well, healthy aging, natural aging and
      successful aging) discussed; (3) which of the issues flagged as important in the
      2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical
      Activity are covered in the newspaper coverage of active aging and synonymous
      terms; (4) which social groups were mentioned in the newspapers covered. The
      study found a total absence of mentioning of the two key documents and a low
      level of coverage of "active aging" and terms conveying similar content. It found
      further a lack of engagement with the issues raised in the two key documents and
      a low level of mentioning of socially disadvantages groups. We posit that reading
      the newspapers we covered will not expose the reader to the two key documents and
      the issues linked to aging well including the need to increase physical activity.

PMID- 24317387
TI  - The involvement of girls and boys with bullying: an analysis of gender
      differences.
AB  - This exploratory and cross-sectional study aimed to identify the prevalence of
      bullying in a group of students and analyze the data regarding the gender of
      those involved in the violence. A questionnaire adapted from Olweus was applied
      in seven elementary education schools in Portugal. The sample consisted of 387
      students between 7 and 14 years old. Data are presented in terms of descriptive
      statistics and differences between proportions were analyzed using chi-square
      tests. The gender analysis of victimization and aggression shows that boys and
      girls are both victims and aggressors, and there are significant differences in
      involvement in bullying between genders and the roles played. Boys are victims
      more often when considering different types of bullying, although significant
      differences were only found for physical aggression. Strategies that include
      gender roles are a priority for prevention and careful attention to this
      phenomenon in the school context. The questions addressed contribute to a broader
      understanding of the phenomenon, emphasizing the differential participation of
      boys and girls in bullying. 

PMID- 24317388
TI  - Changes in the levels of endothelium-derived coagulation parameters in
      nonalcoholic fatty liver disease.
AB  - In a majority of patients with nonalcoholic fatty liver disease (NAFLD),
      cardiovascular risk factors including diabetes mellitus type 2, abdominal
      obesity, and metabolic syndrome are present. The purpose of this study is to
      investigate the presence of endothelial injury and the changes in coagulation
      parameters in NAFLD patients. For this purpose, plasma levels of von Willebrand
      factor (vWF), thrombomodulin, urokinase plasminogen activator (uPA), plasminogen
      activator inhibitor-1 (PAI-1), and tissue factor pathway inhibitor (TFPI) in
      patients with NAFLD were measured. There was a significant difference in vWF and
      TFPI levels between patient and control groups (P < 0.05). However, no
      statistically significant difference was obtained in PAI-1, uPA, and
      thrombomodulin levels between the two groups (P > 0.05). According to our
      results, an increase in vWF and TFPI levels indicates an endothelial injury in
      NAFLD cases. 

PMID- 24317389
TI  - Khat and synthetic cathinones: a review.
AB  - For centuries, 'khat sessions' have played a key role in the social and cultural
      traditions among several communities around Saudi Arabia and most East African
      countries. The identification of cathinone as the main psychoactive compound of
      khat leaves, exhibiting amphetamine-like pharmacological properties, resulted in
      the synthesis of several derivatives structurally similar to this so-called
      natural amphetamine. Synthetic cathinones were primarily developed for
      therapeutic purposes, but promptly started being misused and extensively abused
      for their euphoric effects. In the mid-2000's, synthetic cathinones emerged in
      the recreational drug markets as legal alternatives ('legal highs') to
      amphetamine, 'ecstasy', or cocaine. Currently, they are sold as 'bath salts' or
      'plant food', under ambiguous labels lacking information about their true
      contents. Cathinone derivatives are conveniently available online or at
      'smartshops' and are much more affordable than the traditional illicit drugs.
      Despite the scarcity of scientific data on these 'legal highs', synthetic
      cathinones use became an increasingly popular practice worldwide. Additionally,
      criminalization of these derivatives is often useless since for each specific
      substance that gets legally controlled, one or more structurally modified analogs
      are introduced into the legal market. Chemically, these substances are
      structurally related to amphetamine. For this reason, cathinone derivatives share
      with this drug both central nervous system stimulating and sympathomimetic
      features. Reports of intoxication and deaths related to the use of 'bath salts'
      have been frequently described over the last years, and several attempts to apply
      a legislative control on synthetic cathinones have been made. However, further
      research on their pharmacological and toxicological properties is fully required
      in order to access the actual potential harm of synthetic cathinones to general
      public health. The present work provides a review on khat and synthetic
      cathinones, concerning their historical background, prevalence, patterns of use,
      legal status, chemistry, pharmacokinetics, pharmacodynamics, and their
      physiological and toxicological effects on animals and humans. 

PMID- 24317391
TI  - Are feelings of peace or depression the drivers of the relationship between
      neighbourhood social fragmentation and mental health in Aotearoa/New Zealand?
AB  - Exploration of the influence of neighbourhood social context on supportive
      relationships and social cohesion is on the rise. Positive social contexts may be
      less stressful for residents, resulting in mental wellbeing and calmness; whereas
      negative contexts may increase stress and deleterious mental health. To examine
      this, we measured the relationship between an Index of Neighbourhood Social
      Fragmentation and overall mental well-being in New Zealand. Then we examined the
      influence of fragmentation on two components of mental health: depression and
      calmness. Increased fragmentation was significantly associated with lower mental
      health scores for the entire population and for females, with similar but
      insignificant trends for males. Increased fragmentation was associated with
      increased depression in both sexes, but not calmness. Depression rather than
      calmness may contribute to the observed association between fragmentation and
      overall mental health. Groups vulnerable to stressful social contexts may be
      prone to depression in fragmented neighbourhoods. Further examination of the
      specific aspects of living in fragmented neighbourhoods which increase depressive
      feelings is warranted. 

PMID- 24317390
TI  - A preliminary study on the construction of double suicide gene delivery vectors
      by mesenchymal stem cells and the in vitro inhibitory effects on SKOV3 cells.
AB  - The aim of the present study was to investigate the efficacy of using human
      umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) as gene delivery
      vectors in the treatment of ovarian cancer. Lentivectors overexpressing cytosine
      deaminase (CD) and herpes simplex virus thymidine kinase (HSV-tk) (pGC-FU-CD-TK)
      were constructed, and confirmed by enzyme digestion, DNA sequence and western
      blotting. Quantitative PCR (PCR) was used to verify the overexpression of the
      fusion gene (CD and HSV-tk). SKOV3 cells were co-cultured with MSCs/tk+CD+ at a
      1:1 ratio, and were then treated with the prodrugs (GCV) and/or 5-fluorocytosine
      (5-FC) at different concentrations, and the cytotoxic effects were evaluated
      using MTT assay and flow cytometry. DNA sequencing demonstrated that the sequence
      of HSV-tk and CD genes were consistent with the objective sequence and western
      blotting verified that the constructed lentivector could produce the HSV-tk/CD
      gene. The packed titer was 2.00e+8 TU/ml. The pGC-FU-CD-TK could be stably
      transferred to hUCB-MSCs, and the infection efficiency was almost 80%. RT-PCR
      demonstrated that the expression levels of the HSV-tk/CD fusion gene in
      MSCs/tk+CD+ group was 75 times that in the negative control (P<0.05). Compared
      with GCV or 5-FC alone, the growth inhibition rate (GIR) was significantly higher
      in the combined treatment (F=85.35, P<0.05). The reconstructed MSCs/tk+CD+
      vectors were capable of slowing down the growth of human SKOV3 cells in the
      presence of prodrugs in vitro. The use of combination chemotherapy exhibited a
      more significant inhibitory effect than using a single prodrug.

PMID- 24317392
TI  - A new KIT mutation (N505I) in acral melanoma confers constitutive signaling,
      favors tumorigenic properties, and is sensitive to imatinib.

PMID- 24317393
TI  - Reversal of murine epidermal atrophy by topical modulation of calcium signaling.
AB  - Cytosolic Ca(2+) signals are performed by Ca(2+) releases from the endoplasmic
      reticulum and Ca(2+) influx from the extracellular medium. Releases rely on the
      refilling of the intracellular Ca(2+) stores by the Ca(2+) influx "Store-Operated
      Calcium Entry" (SOCE) via the channel Orai1. Here we show that Orai1 expression,
      SOCE amplitude, and epidermal proliferation are decreased in the epidermis of
      patients with skin fragility when compared with aged nonatrophic skin. Epidermal
      atrophy was induced in mice by the inhibition of Orai1 with small interfering RNA
      and the topical application of a SOCE blocker BTP2. The inhibition of Orai1
      impaired the heparin-binding epidermal growth factor (HB-EGF)-induced Ca(2+)
      influxes and fully prevented the mitogen effect of HB-EGF in primary human
      keratinocytes. Importantly, epidermal proliferation correlated with Orai1
      expression in mice. Conversely, the topical application of an Orai1 activator,
      the benzohydroquinone (BHQ), increased the epidermal thickness and proliferation,
      whereas the pro-proliferative effect of BHQ was prevented by the inhibition of
      Orai1. Finally, the topical application of BHQ reversed the epidermal atrophy
      induced by corticosteroids in mice. The topical modulation of Ca(2+) signals may
      thus be a promising therapeutic strategy in dermatology.

PMID- 24317394
TI  - Patient-specific naturally gene-reverted induced pluripotent stem cells in
      recessive dystrophic epidermolysis bullosa.
AB  - Spontaneous reversion of disease-causing mutations has been observed in some
      genetic disorders. In our clinical observations of severe generalized recessive
      dystrophic epidermolysis bullosa (RDEB), a currently incurable blistering
      genodermatosis caused by loss-of-function mutations in COL7A1 that results in a
      deficit of type VII collagen (C7), we have observed patches of healthy-appearing
      skin on some individuals. When biopsied, this skin revealed somatic mosaicism
      resulting in the self-correction of C7 deficiency. We believe this source of
      cells could represent an opportunity for translational 'natural' gene therapy. We
      show that revertant RDEB keratinocytes expressing functional C7 can be
      reprogrammed into induced pluripotent stem cells (iPSCs) and that self-corrected
      RDEB iPSCs can be induced to differentiate into either epidermal or hematopoietic
      cell populations. Our results give proof-of-principle that an inexhaustible
      supply of functional patient-specific revertant cells can be obtained-
      potentially relevant to local wound therapy and systemic hematopoietic cell
      transplantation. This technology may also avoid some of the major limitations of
      other cell therapy strategies, e.g., immune rejection and insertional
      mutagenesis, which are associated with viral- and nonviral-mediated gene therapy.
      We believe this approach should be the starting point for autologous cellular
      therapies using 'natural' gene therapy in RDEB and other diseases.

PMID- 24317395
TI  - In vivo induction of cutaneous inflammation results in the accumulation of
      extracellular trap-forming neutrophils expressing RORgammat and IL-17.
AB  - Clinical trials successfully using antibodies targeting IL-17 in psoriasis
      support the importance of IL-17 in the pathophysiology of this disease. However,
      there is a debate concerning the source and dynamics of IL-17 production in
      inflamed skin. Here we characterized IL-17-producing immune cells over time,
      using two established in vivo models of human skin inflammation that share many
      histological features with psoriasis, i.e., leukotriene B4 application and tape
      stripping. Both treatments revealed a clear influx of neutrophils and T cells.
      Staining for IL-17 revealed that the majority of IL-17 was expressed by
      neutrophils and mast cells, in both models. Neutrophils, but not mast cells,
      coexpressed the IL-17-associated transcription factor RORgammat and were able to
      form extracellular traps. While the presence of mast cells remained steady during
      the skin inflammatory process, the presence of neutrophils was clearly dynamic in
      time. Therefore, it is attractive to hypothesize that IL-17+/RORgammat+
      neutrophils contribute to human skin inflammation in vivo and possibly to the
      pathogenesis of skin diseases such as psoriasis. Surprisingly, T cells
      represented a minority of the IL-17-expressing cell population. These
      observations challenge the classical opinion that IL-17 is predominantly
      associated with T cells in skin inflammation. 

PMID- 24317396
TI  - Revealing the genetic basis of natural bacterial phenotypic divergence.
AB  - Divergent phenotypes for distantly related strains of bacteria, such as differing
      antibiotic resistances or organic solvent tolerances, are of keen interest both
      from an evolutionary perspective and for the engineering of novel microbial
      organisms and consortia in synthetic biology applications. A prerequisite for any
      practical application of this phenotypic diversity is knowledge of the genetic
      determinants for each trait of interest. Sequence divergence between strains is
      often so extensive as to make brute-force approaches to identifying the loci
      contributing to a given trait impractical. Here we describe a global linkage
      analysis approach, GLINT, for rapid discovery of the causal genetic variants
      underlying phenotypic divergence between distantly related strains of Escherichia
      coli. This general strategy will also be usable, with minor modifications, for
      revealing genotype-phenotype associations between naturally occurring strains of
      other bacterial species. 

PMID- 24317397
TI  - Nonredundant roles for cytochrome c2 and two high-potential iron-sulfur proteins
      in the photoferrotroph Rhodopseudomonas palustris TIE-1.
AB  - The purple bacterium Rhodopseudomonas palustris TIE-1 expresses multiple small
      high-potential redox proteins during photoautotrophic growth, including two high
      potential iron-sulfur proteins (HiPIPs) (PioC and Rpal_4085) and a cytochrome c2.
      We evaluated the role of these proteins in TIE-1 through genetic, physiological,
      and biochemical analyses. Deleting the gene encoding cytochrome c2 resulted in a
      loss of photosynthetic ability by TIE-1, indicating that this protein cannot be
      replaced by either HiPIP in cyclic electron flow. PioC was previously implicated
      in photoferrotrophy, an unusual form of photosynthesis in which reducing power is
      provided through ferrous iron oxidation. Using cyclic voltammetry (CV), electron
      paramagnetic resonance (EPR) spectroscopy, and flash-induced spectrometry, we
      show that PioC has a midpoint potential of 450 mV, contains all the typical
      features of a HiPIP, and can reduce the reaction centers of membrane suspensions
      in a light-dependent manner at a much lower rate than cytochrome c2. These data
      support the hypothesis that PioC linearly transfers electrons from iron, while
      cytochrome c2 is required for cyclic electron flow. Rpal_4085, despite having
      spectroscopic characteristics and a reduction potential similar to those of PioC,
      is unable to reduce the reaction center. Rpal_4085 is upregulated by the divalent
      metals Fe(II), Ni(II), and Co(II), suggesting that it might play a role in
      sensing or oxidizing metals in the periplasm. Taken together, our results suggest
      that these three small electron transfer proteins perform different functions in
      the cell. 

PMID- 24317398
TI  - The uptake hydrogenase in the unicellular diazotrophic cyanobacterium Cyanothece
      sp. strain PCC 7822 protects nitrogenase from oxygen toxicity.
AB  - Cyanothece sp. strain PCC 7822 is a unicellular, diazotrophic cyanobacterium that
      can produce large quantities of H2 when grown diazotrophically. This strain is
      also capable of genetic manipulations and can represent a good model for
      improving H2 production from cyanobacteria. To this end, a knockout mutation was
      made in the hupL gene (DeltahupL), and we determined how this would affect the
      amount of H2 produced. The DeltahupL mutant demonstrated virtually no nitrogenase
      activity or H2 production when grown under N2-fixing conditions. To ensure that
      this mutation only affected the hupL gene, a complementation strain was
      constructed readily with wild-type properties; this indicated that the original
      insertion was only in hupL. The mutant had no uptake hydrogenase activity but had
      increased bidirectional hydrogenase (Hox) activity. Western blotting and
      immunocytochemistry under the electron microscope indicated that the mutant had
      neither HupL nor NifHDK, although the nif genes were transcribed. Interestingly,
      biochemical analysis demonstrated that both HupL and NifH could be membrane
      associated. The results indicated that the nif genes were transcribed but that
      NifHDK was either not translated or was translated but rapidly degraded. We
      hypothesized that the Nif proteins were made but were unusually susceptible to O2
      damage. Thus, we grew the mutant cells under anaerobic conditions and found that
      they grew well under N2-fixing conditions. We conclude that in unicellular
      diazotrophs, like Cyanothece sp. strain PCC 7822, the HupLS complex helps remove
      oxygen from the nitrogenase, and that this is a more important function than
      merely oxidizing the H2 produced by the nitrogenase. 

PMID- 24317400
TI  - Cell growth inhibition upon deletion of four toxin-antitoxin loci from the
      megaplasmids of Sinorhizobium meliloti.
AB  - Toxin and antitoxin (TA) gene pairs are addiction systems that are present in
      many microbial genomes. Sinorhizobium meliloti is an N2-fixing bacterial symbiont
      of alfalfa and other leguminous plants, and its genome consists of three large
      replicons, a circular chromosome (3.7 Mb) and the megaplasmids pSymA (1.4 Mb) and
      pSymB (1.7 Mb). S. meliloti carries 211 predicted type II TA genes, each encoding
      a toxin or an antitoxin. We constructed defined deletion strains that
      collectively removed the entire pSymA and pSymB megaplasmids except for their
      oriV regions. Of approximately 100 TA genes on pSymA and pSymB, we identified
      four whose loss was associated with cell death or stasis unless copies of the
      genes were supplied in trans. Orthologs of three of these loci have been
      characterized in other organisms (relB/E [sma0471/sma0473], Fic [DOC] [sma2105],
      and VapC [PIN] [orf2230/sma2231]), and this report contains the first
      experimental proof that RES/Xre (smb21127/smb21128) loci can function as a TA
      system. Transcriptome sequencing (RNA-seq) analysis did not reveal
      transcriptional differences between the TA systems to account for why deletion of
      the four "active" systems resulted in cell toxicity. These data suggest that
      severe cell growth phenotypes result from the loss of a few TA systems and that
      loss of most TA systems may result in more subtle phenotypes. These four TA
      systems do not appear to play a direct role in the S. meliloti-alfalfa symbiosis,
      as strains lacking these TA systems had a symbiotic N2 fixation phenotype that
      was indistinguishable from the wild type. 

PMID- 24317399
TI  - Structural modeling and physicochemical characterization provide evidence that
      P66 forms a beta-barrel in the Borrelia burgdorferi outer membrane.
AB  - The Borrelia burgdorferi outer membrane (OM) contains numerous surface-exposed
      lipoproteins but a relatively low density of integral OM proteins (OMPs). Few
      membrane-spanning OMPs of B. burgdorferi have been definitively identified, and
      none are well characterized structurally. Here, we provide evidence that the
      borrelial OMP P66, a known adhesin with pore-forming activity, forms a beta
      barrel in the B. burgdorferi OM. Multiple computer-based algorithms predict that
      P66 forms a beta-barrel with either 22 or 24 transmembrane domains. According to
      our predicted P66 topology, a lysine residue (K487) known to be sensitive to
      trypsin cleavage is located within a surface-exposed loop. When we aligned the
      mature P66 amino acid sequences from B. burgdorferi and B. garinii, we found that
      K487 was present only in the B. burgdorferi P66 protein sequence. When intact
      cells from each strain were treated with trypsin, only B. burgdorferi P66 was
      trypsin sensitive, indicating that K487 is surface exposed, as predicted.
      Consistent with this observation, when we inserted a c-Myc tag adjacent to K487
      and utilized surface localization immunofluorescence, we detected the loop
      containing K487 on the surface of B. burgdorferi. P66 was examined by both Triton
      X-114 phase partitioning and circular dichroism, confirming that the protein is
      amphiphilic and contains extensive (48%) beta-sheets, respectively. Moreover, P66
      also was able to incorporate into liposomes and form channels in large
      unilamellar vesicles. Finally, blue native PAGE (BN-PAGE) revealed that under
      nondenaturing conditions, P66 is found in large complexes of ~400 kDa and ~600
      kDa. Outer surface lipoprotein A (OspA) and OspB both coimmunoprecipitate with
      P66, demonstrating that P66 associates with OspA and OspB in B. burgdorferi. The
      combined computer-based structural analyses and supporting physicochemical
      properties of P66 provide a working model to further examine the porin and
      integrin-binding activities of this OMP as they relate to B. burgdorferi
      physiology and Lyme disease pathogenesis. 

PMID- 24317401
TI  - Essentiality of DevR/DosR interaction with SigA for the dormancy survival program
      in Mycobacterium tuberculosis.
AB  - The DevR/DosR regulator is believed to play a key role in dormancy adaptation
      mechanisms of Mycobacterium tuberculosis in response to a multitude of gaseous
      stresses, including hypoxia, which prevails within granulomas. DevR activates
      transcription by binding to target promoters containing a minimum of two binding
      sites. The proximal site overlaps with the SigA -35 element, suggesting that DevR
      SigA interaction is required for activating transcription. We evaluated the roles
      of 14 charged residues of DevR in transcriptional activation under hypoxic
      stress. Seven of the 14 alanine substitution mutants were defective in regulon
      activation, of which K191A, R197A, and K179A+K168A (designated K179A*) mutants
      were significantly or completely compromised in DNA binding. Four mutants,
      namely, E154A, R155A, E178A, and K208A, were activation defective in spite of
      binding to DNA and were classified as positive-control (pc) mutants. The SigA
      interaction defect of the E154A and E178A proteins was established by in vitro
      and in vivo assays and implies that these substitutions lead to an activation
      defect because they disrupt an interaction(s) with SigA. The relevance of DevR
      interaction to the transcriptional machinery was further established by the
      hypoxia survival phenotype displayed by SigA interaction-defective mutants. Our
      findings demonstrate the role of DevR-SigA interaction in the activation
      mechanism and in bacterial survival under hypoxia and establish the housekeeping
      sigma factor SigA as a molecular target of DevR. The interaction of DevR and RNA
      polymerase suggests a new and novel interceptable molecular interface for future
      antidormancy strategies for Mycobacterium tuberculosis. 

PMID- 24317402
TI  - An rhs gene linked to the second type VI secretion cluster is a feature of the
      Pseudomonas aeruginosa strain PA14.
AB  - The type VI secretion system (T6SS) of Gram-negative bacteria has been involved
      in various processes, notably bacterial competition and eukaryotic cell
      subversion. Most Pseudomonas aeruginosa strains possess three T6SS gene clusters,
      but only the function of the first T6SS (H1-T6SS) has been clearly elucidated. It
      is involved in the secretion of three toxins (Tse1 to -3) that target bacterial
      competitors. In the case of the H2- and H3-T6SS, no clear function has been
      assigned, and only one effector has been associated with these systems. Yet the
      H2-T6SS was proposed to promote P. aeruginosa internalization in nonphagocytic
      epithelial cells. Although the H2-T6SS genetic organization is conserved across
      P. aeruginosa isolates, one feature is the presence of an additional
      transcriptional unit in the PA14 strain H2-T6SS cluster, which is divergent from
      the core H2-T6SS genes. A specific set of four genes encodes an Hcp protein
      (Hcp2), a VgrG protein (VgrG14), an Rhs element (PA14_43100 or RhsP2), and a
      protein with no homologies with previously characterized proteins (PA14_43090).
      In this study, we engineered a P. aeruginosa PA14 strain carrying an arabinose
      inducible H2-T6SS on the chromosome. We showed that arabinose induction readily
      promotes assembly of the H2-T6SS, as seen by monitoring Hcp2 secretion. We
      further studied the secretion fate of VgrG14 and RhsP2, but these were not
      detectable in the extracellular medium. We finally investigated whether
      activation of the PA14 H2-T6SS gene cluster could influence phenotypic traits
      such as internalization in eukaryotic cells, and we reported noteworthy
      differences compared to strain PAO1, which may be accounted for by the described
      genetic differences. 

PMID- 24317403
TI  - Regulation of the response regulator gene degU through the binding of SinR/SlrR
      and exclusion of SinR/SlrR by DegU in Bacillus subtilis.
AB  - Bacillus subtilis DegU is a response regulator of the DegS-DegU two-component
      regulatory system. Phosphorylated DegU (DegU-P) controls many genes and
      biological processes, such as exoprotease and gamma-polyglutamic acid production,
      in addition to the degU gene, by binding to target gene promoters.
      Nonphosphorylated DegU and low levels of DegU-P are required for swarming
      motility and genetic competence. The DNA-binding repressors SinR and SlrR are
      part of a double-negative feedback loop and comprise the epigenetic switch
      governing biofilm formation. In this study, we found that SinR repressed degU.
      Furthermore, SlrR, which interacts with SinR through protein-protein interaction,
      seems to have an active role in degU expression in in vivo lacZ analysis. An in
      vitro transcription assay supported this observation. An electrophoretic mobility
      shift assay (EMSA) showed that SinR bound to the degU promoter and that SlrR
      formed a complex with SinR on the degU promoter. In EMSA, DegU-P excluded the
      SinR/SlrR complex but not SinR from the degU promoter in the presence of RNA
      polymerase. These findings suggest that DegU-P interacts with SlrR. In support of
      this hypothesis, disruption of the slrR gene resulted in decreased degU
      expression. This newly identified regulatory mechanism for degU is considered to
      be sequential transcription factor replacement. 

PMID- 24317404
TI  - Identification of 3-sulfinopropionyl coenzyme A (CoA) desulfinases within the
      Acyl-CoA dehydrogenase superfamily.
AB  - In a previous study, the essential role of 3-sulfinopropionyl coenzyme A (3SP
      CoA) desulfinase acyl-CoA dehydrogenase (Acd) in Advenella mimigardefordensis
      strain DPN7(T) (AcdDPN7) during degradation of 3,3'-dithiodipropionic acid (DTDP)
      was elucidated. DTDP is a sulfur-containing precursor substrate for biosynthesis
      of polythioesters (PTEs). AcdDPN7 showed high amino acid sequence similarity to
      acyl-CoA dehydrogenases but was unable to catalyze a dehydrogenation reaction.
      Hence, it was investigated in the present study whether 3SP-CoA desulfinase
      activity is an uncommon or a widespread property within the acyl-CoA
      dehydrogenase superfamily. Therefore, proteins of the acyl-CoA dehydrogenase
      superfamily from Advenella kashmirensis WT001, Bacillus cereus DSM31, Cupriavidus
      necator N-1, Escherichia coli BL21, Pseudomonas putida KT2440, Burkholderia
      xenovorans LB400, Ralstonia eutropha H16, Variovorax paradoxus B4, Variovorax
      paradoxus S110, and Variovorax paradoxus TBEA6 were expressed in E. coli strains.
      All purified acyl-CoA dehydrogenases appeared as homotetramers, as revealed by
      size exclusion chromatography. AcdS110, AcdB4, AcdH16, and AcdKT2440 were able to
      dehydrogenate isobutyryl-CoA. AcdKT2440 additionally dehydrogenated butyryl-CoA
      and valeryl-CoA, whereas AcdDSM31 dehydrogenated only butyryl-CoA and valeryl
      CoA. No dehydrogenation reactions were observed with propionyl-CoA, isovaleryl
      CoA, succinyl-CoA, and glutaryl-CoA for any of the investigated acyl-CoA
      dehydrogenases. Only AcdTBEA6, AcdN-1, and AcdLB400 desulfinated 3SP-CoA and were
      thus identified as 3SP-CoA desulfinases within the acyl-CoA dehydrogenase family,
      although none of these three Acds dehydrogenated any of the tested acyl-CoA
      thioesters. No appropriate substrates were identified for AcdBL21 and AcdWT001.
      Spectrophotometric assays provided apparent Km and Vmax values for active
      substrates and indicated the applicability of phylogenetic analyses to predict
      the substrate range of uncharacterized acyl-CoA dehydrogenases. Furthermore, C.
      necator N-1 was found to utilize 3SP as the sole source of carbon and energy. 

PMID- 24317405
TI  - Molecular and biochemical characterization of dehydroascorbate reductase from a
      stress adapted C4 plant, pearl millet [Pennisetum glaucum (L.) R. Br].
AB  - KEY MESSAGE: PgDHAR was isolated from Pennisetum glaucum. PgDHAR responded to
      abiotic stress and exhibited enzyme activity at broad ranges of temperature, pH
      and substrate concentrations suggesting its role in stress tolerance. ABSTRACT:
      Dehydroascorbate reductase (EC 1.8.5.1) is a crucial enzyme actively involved in
      the recycling of ascorbate redox pool in the cellular environment. In this study,
      the full-length cDNA coding for DHAR polypeptide and its corresponding gene was
      isolated from Pennisetum glaucum (PgDHAR). PgDHAR encodes a polypeptide of 213
      amino acids with a predicted molecular mass of 23.4 kDa and shares 80-75 %
      sequence homology with DHAR from other plants. The heterologously expressed
      recombinant PgDHAR protein exhibited activity in a wide range of substrate
      concentrations. The recombinant PgDHAR is thermostable and retains its activity
      over a broad pH range. Furthermore, transcript level of PgDHAR is quantitatively
      up-regulated in response to temperature. On the whole, PgDHAR alone or in
      combination with other genes of ascorbate-glutathione cycle can be used for the
      development of stress tolerant as well as nutritionally improved food crop with
      enhanced ascorbic acid content.

PMID- 24317406
TI  - Leveraging text messaging and mobile technology to support pediatric obesity
      related behavior change: a qualitative study using parent focus groups and
      interviews.
AB  - BACKGROUND: Text messaging (short message service, SMS) is a widely accessible
      and potentially cost-effective medium for encouraging behavior change. Few
      studies have examined text messaging interventions to influence child health
      behaviors or explored parental perceptions of mobile technologies to support
      behavior change among children. OBJECTIVE: Our aim was to examine parental
      acceptability and preferences for text messaging to support pediatric obesity
      related behavior change. METHODS: We conducted focus groups and follow-up
      interviews with parents of overweight and obese children, aged 6-12 years, seen
      for "well-child" care in eastern Massachusetts. A professional moderator used a
      semistructured discussion guide and sample text messages to catalyze group
      discussions. Seven participants then received 3 weeks of text messages before a
      follow-up one-on-one telephone interview. All focus groups and interviews were
      recorded and transcribed verbatim. Using a framework analysis approach, we
      systematically coded and analyzed group and interview data to identify salient
      and convergent themes. RESULTS: We reached thematic saturation after five focus
      groups and seven follow-up interviews with a total of 31 parents of diverse
      race/ethnicity and education levels. Parents were generally enthusiastic about
      receiving text messages to support healthy behaviors for their children and
      preferred them to paper or email communication because they are brief and
      difficult to ignore. Participants anticipated high responsiveness to messaging
      endorsed by their child's doctor and indicated they would appreciate messages 2-3
      times/week or more as long as content remains relevant. Suggestions for
      maintaining message relevance included providing specific strategies for
      implementation and personalizing information. Most felt the negative features of
      text messaging (eg, limited message size) could be overcome by providing links
      within messages to other media including email or websites. CONCLUSIONS: Text
      messaging is a promising medium for supporting pediatric obesity-related behavior
      change. Parent perspectives could assist in the design of text-based
      interventions. TRIAL REGISTRATION: Clinicaltrials.gov NCT01565161;
      http://clinicaltrials.gov/show/NCT01565161 (Archived by WebCite at
      http://www.webcitation.org/6LSaqFyPP).

PMID- 24317407
TI  - The paraventricular nucleus and heart failure.
AB  - NEW FINDINGS: What is the topic of this review? This review gives an update on
      the cellular and molecular mechanisms within the autonomic nervous system
      involved in non-pathological and pathological cardiovascular regulation. What
      advances does it highlight? For cardiovascular homeostasis in non-pathological
      conditions to be maintained, discrete neural networks using specified signalling
      mechanisms at both cellular and molecular levels are required. In heart failure,
      the cell signalling protein partners CAPON and PIN decrease the bioavailability
      of nitric oxide by inhibiting neuronal nitric oxide synthase activity, leading to
      the removal of tonic neuronal inhibition. Following a myocardial infarction, pro
      inflammatory cytokines in the paraventricular nucleus and the subsequent
      generation of reactive oxygen species, via angiotensin II activation of the
      angiotensin II type 1 receptor, increase neuronal excitability further, leading
      to sympathetic excitation. A pathological feature of heart failure is abnormal
      control of the sympathetic nervous system. The paraventricular nucleus of the
      hypothalamus (PVN) is one of the most important central sites involved in
      regulating sympathetic tone and is, in part, responsible for the dysregulation of
      the sympathetic nervous system evident in heart failure. Generation of
      sympathetic tone in response to fluctuations in cardiovascular regulation uses
      discrete anatomical pathways and neurochemical modulators. Direct and indirect
      projections from the PVN pre-autonomic neurons innervate the sympathetic
      preganglionic neurons in the spinal cord, which in turn innervate sympathetic
      ganglia that give rise to the sympathetic nerves. Pre-autonomic neurons of the
      PVN themselves receive an afferent input arising from the nucleus tractus
      solitarii, and viscerosensory receptors convey cardiovascular fluctuations to the
      nucleus tractus solitarii. The PVN contains excitatory and inhibitory neurons,
      whose balance determines the sympathetic tone. In non-pathological conditions,
      the tonic inhibition of the PVN pre-autonomic neurons is mediated by GABA- and NO
      releasing neurons. In heart failure, the pre-autonomic neurons are disinhibited
      by the actions of the excitatory neurotransmitters glutamate and angiotensin II,
      leading to increased sympathetic activity. A key feature of the disinhibition is
      a reduction in the bioavailability of NO as a consequence of disrupted CAPON and
      PIN signalling mechanisms within the neuron. Another critical feature that
      contributes to increased neuronal excitation within the PVN is the production of
      pro-inflammatory cytokines immediately following a myocardial infarction, the
      activation of the angiotensin II type 1 receptor and the production of reactive
      oxygen species. By examining the changes associated with the sympathetic nervous
      system pathway, we will progress our understanding of sympathetic regulation in
      heart failure, identify gaps in our knowledge and suggest new therapeutic
      strategies.

PMID- 24317408
TI  - Myometrial physiology--time to translate?
AB  - In this short review, we discuss how recent insights into myometrial physiology
      may be taken forward and translated into much-needed novel therapies for problems
      associated with labour. We consider excitation-contraction coupling in the
      myometrium and how this relates to our understanding of the changes that occur to
      produce myometrial contractions and successful labour. We then discuss how this
      information has already been used in the development of drugs to either stimulate
      or relax the myometrium, to address the needs of women with either slow
      (dystocic) labours or threatened preterm labours, respectively. We next present
      the data showing how basic physiological findings pertaining to hypoxia and
      lactate production have been taken and translated into a tool for predicting and
      thus better managing difficult labours. We then highlight examples of where
      physiological research has started to provide mechanistic insight into clinical
      problems associated with labour and parturition (obesity, diabetes, advanced
      maternal age, postdate and twin pregnancies) and suggest how these findings could
      be translated into new therapies for difficult labours. 

PMID- 24317409
TI  - Index selection for genetic improvement of quantitative characters.
AB  - This paper reviews the basic theory and summarizes various modifications of the
      selection index. The limitations of selection index are discussed in four parts:
      (1) changes of parameters due to selection. (2) sampling errors of parameter
      estimation. (3) evaluation of relative economic weights and (4) internal
      deterrents to index selection. 

PMID- 24317410
TI  - The allelic distribution at an acid phosphatase locus in Norway spruce (Picea
      abies) along similar climatic gradients.
AB  - The allele frequency distribution at a polymorphic acid phosphatase locus (APH-B)
      was determined in natural populations of Norway spruce (Picea abies) from a
      latitudinal transect in Finland, an altitudinal transect in the Austrian Alps,
      and from different locations of the Swiss range. The three independent population
      groups, selected with respect to similar climatic gradients, were studied to
      detect the forces that cause the geographic variation at the APH-B locus.In
      almost all of the populations investigated, four alleles (APH-B1 - B4) could be
      identified at this enzyme locus, however, the alleles b1 and B2, as well as B3
      and B4, show a great similarity according to their phenotypic appearance after
      electrophoresis as well as to their frequency distributions along the different
      transects. With the aid of some theoretical considerations and data comparisons,
      a selective equivalence of the alleles B1 and B2, as well as B3 and B4, could be
      ascertained, thus reducing the number of alleles that can respond differently to
      natural selection.After combining the frequencies of the selectively equivalent
      alleles, similar clinal variation patterns could be observed along the different
      geographical transects, where-by the frequency of the allele group APH-B1 /B2
      markedly increases with latitudes in Finland and towards higher elevations in the
      Alps. Correspondingly, the allele group APH-B3/B4 predominates in the southern
      parts of Finland and in the lowlands and foothills of Austria and Switzerland. It
      is therefore concluded that natural selection causes the geographic variation
      pattern at the APH-B locus and that one or several temperature variables function
      as an at least predominant selective force. Possible relationships between this
      enzyme polymorphism and other tree characters and the physiological role of acid
      phosphatases in tree adaptation were discussed. 

PMID- 24317411
TI  - Genetical analysis of components of overall plant shape.
AB  - The genetical control of six characters, which were taken as jointly reflecting
      the overall shape of the plant, was analysed using four true-breeding lines of
      Nicotiana rustica. F1 F2 and first backcross generations were raised from all of
      the possible pairwise combinations between the lines. The particular
      relationships between the lines provided a basis for the analysis which was an
      extension of the normal model fitting procedures described by Mather and Jinks
      (1971).The first step in the analysis was to test whether the allelic differences
      present between the inbred lines p1 and P5 had been maintained in the two lines
      B2 and B35, derived from an earlier cross between the former. If the allelic
      differences between p1 and P5 were present between B2 and B35, it was possible to
      proceed straight-forwardly by fitting a model consisting of m, two symmetrical
      [d]'s and the relevant non-additive parameters. If B2 and B35 were homozygous for
      the same alleles at loci by which p1 and P5 differed, in other words if
      significant asymmetry in the gene distributions was present, the model had to be
      extended to cover the effects of such genes.All six characters investigated were
      shown to be subject to genetical variation. From the composition of the genetical
      models that were necessary to account for the observations from each of the
      characters, it was inferred that they should be amenable to at least partially
      independent adjustment by selection. 

PMID- 24317412
TI  - Inheritance of five quantitative characters of bread wheat.
AB  - Heritability estimates of five characters of the wheat plant were studied in five
      crosses involving six cultivars of bread wheat. Parents, F1, F2 and backcrosses
      to both parents were used in the estimation of the genetic
      parameters.Heritability was low for number of fertile spikes/plant, moderate for
      number of spikelets/spike, number of kernels/spike, 1000-kernel weight and
      moderately high for number of kernels/spike. Evidence for mainly nonadditive gene
      effects were observed in the expression of number of fertile spikes and 1000
      kernel weight. Although nonadditives contributed to a lesser degree to the gene
      action, additives seemed to be the most important genetic expression regulating
      number of spikelets/spike, number of kernels/spike, and number of
      kernels/spikelet. Except for number of fertile spikes/plant, selection in F2
      populations seems to be promising. 

PMID- 24317413
TI  - The effect of varying the number of pollen grains used in fertilization.
AB  - The number of pollen grains placed upon a stigma influence both the development
      of pollen tubes and subsequently the progeny which result from fertilizations by
      gametes from these pollen tubes. The first influence is demonstrated by reduced
      pollen tube growth rates when pollen grains are few in number. This may indicate
      direct effects of pollen tubes upon the stylar tissues or perhaps more complex
      interactions between pollen and style. The second and potentially more important
      influence of limited pollination is upon the progeny. This was demonstrated with
      studies on three species. In each case, variation among the resultant plants was
      greater when pollen was limited than when normal, that is excessive, pollen was
      used. The mechanism of this phenomenon is not certain, but our data indicate that
      it is not simply an artefact of variation in seed size. 

PMID- 24317414
TI  - In vitro hybridization by sexual methods and by fusion of somatic protoplasts :
      Experiments with Nicotiana tabacum x Petunia hybrida, N. tabacum x Hyoscyamus
      niger, H. niger x P. hybrida, Melandrium album x P. hybrida.
AB  - 1. No hybrid plants of Nicotiana tabacum + Petunia hybrida were regenerated from
      calluses of fusion experiments with mesophyll protoplasts of N. tabacum s, s (2)
      and v and of P. hybrida mu 1 (2). 2. After in vitro pollination of ovules of N.
      tabacum with pollen of P. hybrida, filamentous proembryos and cellular endosperms
      could be detected. But after 8-10 days, embryos and endosperms degenerated
      completely, indicating a strong zygotic incompatibility of the two genomes. 3.
      After in vitro pollination of ovules of N. tabacum with pollen of Hyoscyamus
      niger, large globular embryos and well developed cellular endosperms are found,
      indicating that the method of in vitro pollination was not the reason for the
      early degeneration of the tobacco x petunia proembryos. The globular embryos of
      (tobacco x henbane) hybrids developed further on in a culture of ovules in a
      special medium 'C'. But then they started to produce callus tissue and did not
      develop normal seeds as (tobacco x tobacco) in vitro self-pollinations were able
      to do. 4. After in vitro pollination of ovules of Melandrium album with pollen of
      N. tabacum, no embryos could be found although several endosperm nuclei could be
      detected. The hybrid chromosome number was not counted. In Melandrium album,
      ovules pollinated with P. hybrida divisions of nuclei of the mother plant and the
      generative nucleus of the father could be photographed. No further development
      took place. 

PMID- 24317415
TI  - Some statistical properties of an index of multiple traits.
AB  - Hazel (1943) defined a selection index that maximizes the correlation, RIH,
      between the index, I=SigmabiXi and its aggregate genetic value, H=Sigmaaigi,
      where the bi's are the derived coefficients of the observed traits, Xi, the ai's
      are their relative economic values and the gi's are their respective breeding
      values. This is called an optimum index. The expected value of the index is not H
      but rather K=Sigmabigi. The ratio of RHI/RKI is always less than or equal to 1.0.
      With selection on I, the ratio of the change in K to the change in H is the true
      heritability of the indez, that is, h I (2) =Delta(K)/DeltaH. This is not the
      same as R IH (2) , which serves only as the predictor of the change in H with
      selection on I. If the index, I, itself is considered as a unit trait, studies
      can then be made of correlated response in I when selection is based only on a
      single trait in the index. I is then called a performance index. This approach
      provides for additional insight into the question of the failure of selection to
      make gains in total performance over many generations. 

PMID- 24317416
TI  - Water-stable metal-organic frameworks with intrinsic peroxidase-like catalytic
      activity as a colorimetric biosensing platform.
AB  - Two iron(III)-based metal-organic frameworks (MOFs) are found to behave as
      efficient peroxidase mimics and catalyze the oxidation of different peroxidase
      substrates by H2O2 accompanied with significant color change in the solution.
      With these findings, a simple and sensitive colorimetric assay to detect H2O2 and
      ascorbic acid has been established.

PMID- 24317417
TI  - Development and validation of two liquid chromatography-tandem mass spectrometry
      methods for the determination of silibinin and silibinin hemisuccinate in human
      plasma.
AB  - To investigate the pharmacokinetics of silibinin and silibinin hemisuccinate in
      human plasma, two high-performance liquid chromatography-tandem mass spectrometry
      (HPLC-MS/MS) methods were developed and validated. The methods require a small
      volume of sample (100MUL), and the recovery of the analytes was complete with a
      good reproducibility (CV% 1.7-9.5), after a simple protein precipitation.
      Naringenin was used as internal standard. The chromatographic methods provided a
      good separation of diastereoisomers A and B of both silibinin and silibinin
      hemisuccinate onto a Chromolith Performance RP18e 100mm*3mm column, with a
      resolution of peaks from plasma matrix in less than 6min. The methods precision
      values expressed as CV% were always <=6.2% and the accuracy was always well
      within the acceptable 15% range. Quantification was performed on a triple
      quadrupole tandem mass spectrometer by Selected Reaction Monitoring (SRM) mode,
      in a negative ion mode, via electrospray ionization (ESI). The lower limit of
      quantitation was set at 5.0ng/mL (silibinin) and 25.0ng/mL (silibinin
      hemisuccinate), and the linearity was validated up to 1000.0 and 12,500.0ng/mL,
      for silibinin and silibinin hemisuccinate, respectively, with correlation
      coefficients (R(2)) of 0.991 or better. The methods were suitable for
      pharmacokinetic studies and were successfully applied to human plasma samples
      from subjects treated intravenously with Legalon((r)) SIL at the dose of 20mg/kg,
      expressed as silibinin. 

PMID- 24317418
TI  - Tyrosinase immobilized enzyme reactor: development and evaluation.
AB  - Immobilized enzyme reactors of tyrosinase (tyr-IMERs) for use on-line in HPLC
      system were prepared by different procedures and then compared. The enzyme,
      obtained from Agaricus bisporus, was immobilized on epoxy-silica which was
      prepared using different conditions. Enzyme immobilization was conducted by both
      in situ and in batch techniques. The different procedures were compared in terms
      of protein and activity retention, IMERs activity, kinetics and stability. The
      influence of immobilization procedure on enzyme activity and the behavior of the
      IMERs against a standard inhibitor were also investigated. In situ immobilization
      on epoxy-silica, synthesized using microwave assistance, provided the best
      conditions to prepare tyrosinase IMERs. The tyr-IMERs were successfully tested
      with known and potential inhibitors of tyrosinase, and the results showed that
      they can be used for the screening of inhibitors of that enzyme. 

PMID- 24317419
TI  - Debiasing the mind through meditation: mindfulness and the sunk-cost bias.
AB  - In the research reported here, we investigated the debiasing effect of
      mindfulness meditation on the sunk-cost bias. We conducted four studies (one
      correlational and three experimental); the results suggest that increased
      mindfulness reduces the tendency to allow unrecoverable prior costs to influence
      current decisions. Study 1 served as an initial correlational demonstration of
      the positive relationship between trait mindfulness and resistance to the sunk
      cost bias. Studies 2a and 2b were laboratory experiments examining the effect of
      a mindfulness-meditation induction on increased resistance to the sunk-cost bias.
      In Study 3, we examined the mediating mechanisms of temporal focus and negative
      affect, and we found that the sunk-cost bias was attenuated by drawing one's
      temporal focus away from the future and past and by reducing state negative
      affect, both of which were accomplished through mindfulness meditation. 

PMID- 24317421
TI  - Time, money, and morality.
AB  - Money, a resource that absorbs much daily attention, seems to be involved in much
      unethical behavior, which suggests that money itself may corrupt. This research
      examined a way to offset such potentially deleterious effects-by focusing on
      time, a resource that tends to receive less attention than money but is equally
      ubiquitous in daily life. Across four experiments, we examined whether shifting
      focus onto time can salvage individuals' ethicality. We found that implicitly
      activating the construct of time, rather than money, leads individuals to behave
      more ethically by cheating less. We further found that priming time reduces
      cheating by making people reflect on who they are. Implications for the use of
      time primes in discouraging dishonesty are discussed. 

PMID- 24317422
TI  - Better off than we know: distorted perceptions of incomes and income inequality
      in America.
AB  - Three studies examined Americans' perceptions of incomes and income inequality
      using a variety of criterion measures. Contrary to recent findings indicating
      that Americans underestimate wealth inequality, we found that Americans not only
      overestimated the rise of income inequality over time, but also underestimated
      average incomes. Thus, economic conditions in America are more favorable than
      people seem to realize. Furthermore, ideological differences emerged in two of
      these studies, such that political liberals overestimated the rise of inequality
      more than political conservatives. Implications of these findings for public
      policy debates and ideological disagreements are discussed. 

PMID- 24317420
TI  - Nonconscious emotional activation colors first impressions: a regulatory role for
      conscious awareness.
AB  - Emotions can color people's attitudes toward unrelated objects in the
      environment. Existing evidence suggests that such emotional coloring is
      particularly strong when emotion-triggering information escapes conscious
      awareness. But is emotional reactivity stronger after nonconscious emotional
      provocation than after conscious emotional provocation, or does conscious
      processing specifically change the association between emotional reactivity and
      evaluations of unrelated objects? In this study, we independently indexed
      emotional reactivity and coloring as a function of emotional-stimulus awareness
      to disentangle these accounts. Specifically, we recorded skin-conductance
      responses to spiders and fearful faces, along with subsequent preferences for
      novel neutral faces during visually aware and unaware states. Fearful faces
      increased skin-conductance responses comparably in both stimulus-aware and
      stimulus-unaware conditions. Yet only when visual awareness was precluded did
      skin-conductance responses to fearful faces predict decreased likability of
      neutral faces. These findings suggest a regulatory role for conscious awareness
      in breaking otherwise automatic associations between physiological reactivity and
      evaluative emotional responses. 

PMID- 24317423
TI  - Show me the numbers: precision as a cue to others' confidence.

PMID- 24317424
TI  - Dissociation between saliency signals and activity in early visual cortex.
AB  - Saliency is a measure that describes how attention is guided by local stimulus
      properties. Some hypotheses assign its computation to specific topographically
      organized areas of early human visual cortex. However, in most stimuli, saliency
      is correlated with luminance contrast, which in turn is known to correlate with
      activity in these early areas. Thus, any observed correlation of local activity
      with saliency might be due to the area encoding luminance contrast. Here we
      disentangle encoding of local luminance contrast and saliency by using stimuli
      where the two properties are uncorrelated. First, we conducted an eye-tracking
      study to verify that both negative and positive contrast modifications located in
      individual quadrants of the visual field increase saliency. Second, subjects
      viewed identical stimuli while fMRI signals were recorded. We find that positive
      contrast modifications induce a robust increase of activity in V1-V3 and hV4.
      However, negative contrast modifications lead to a reduced (V1, V2) or comparable
      (V3, hV4) activity level compared to unmodified quadrants. Furthermore, even with
      linear multivariate pattern-classification techniques, it is not possible to
      decode the location of the salient quadrant independent of the type of the
      contrast modification. Instead, decoding of the contrast-modified location is
      only possible separately for the two modification types in V1-V3. These findings
      suggest that the BOLD activity in V1-V3 is dominated by contrast-dependent
      processes and does not include the contrast invariance necessary for the
      computation of feature-invariant saliency. 

PMID- 24317425
TI  - Frequency-based heuristics for material perception.
AB  - People often make rapid visual judgments of the properties of surfaces they are
      going to walk on or touch. How do they do this when the interactions of
      illumination geometry with 3-D material structure and object shape result in
      images that inverse optics algorithms cannot resolve without externally imposed
      constraints? A possibly effective strategy would be to use heuristics based on
      information that can be gleaned rapidly from retinal images. By using perceptual
      scaling of a large sample of images, combined with correspondence and canonical
      correlation analyses, we discovered that material properties, such as roughness,
      thickness, and undulations, are characterized by specific scales of luminance
      variations. Using movies, we demonstrate that observers' percepts of these 3-D
      qualities vary continuously as a function of the relative energy in corresponding
      2-D frequency bands. In addition, we show that judgments of roughness, thickness,
      and undulations are predictably altered by adaptation to dynamic noise at the
      corresponding scales. These results establish that the scale of local 3-D
      structure is critical in perceiving material properties, and that relative
      contrast at particular spatial frequencies is important for perceiving the
      critical 3-D structure from shading cues, so that cortical mechanisms for
      estimating material properties could be constructed by combining the parallel
      outputs of sets of frequency-selective neurons. These results also provide
      methods for remote sensing of material properties in machine vision, and rapid
      synthesis, editing and transfer of material properties for computer graphics and
      animation. 

PMID- 24317426
TI  - Meaningful sounds enhance visual sensitivity to human gait regardless of
      synchrony.
AB  - Previous research demonstrates that meaningfully related sounds enhance visual
      sensitivity to point-light displays of human movement. Here we report two
      psychophysical studies that investigated whether, and if so when, this
      facilitation is modulated by the temporal relationship between auditory and
      visual stimuli. In Experiment 1, participants detected point-light walkers in
      masks while listening to footsteps that were either synchronous or out-of-phase
      with point-light footfalls. The relative timing of auditory and visual walking
      did not impact performance. Experiment 2 further tested the importance of
      multisensory timing by disrupting the rhythm of the auditory and visual streams.
      Participants detected point-light walkers while listening to footstep or tone
      sounds that were either synchronous or temporally random with regards to point
      light footfalls. Heard footsteps improved visual sensitivity over heard tones
      regardless of timing. Taken together, these results suggest that during the
      detection of others' actions, the perceptual system makes use of meaningfully
      related sounds whether or not they are synchronous. These results are discussed
      in relation to the unity assumption theory as well as recent empirical data that
      suggest that temporal correspondence is not always a critical factor in
      multisensory perception and integration. 

PMID- 24317427
TI  - Efficient production of (R)-(-)-mandelic acid using glutaraldehyde cross-linked
      Escherichia coli cells expressing Alcaligenes sp. nitrilase.
AB  - Recombinant Escherichia coli cells expressing Alcaligenes sp. nitrilase were
      simply immobilized by direct cross-linking using glutaraldehyde. About 85 % of
      the total nitrilase activity was recovered under the optimal cross-linking
      conditions. The thermal stabilities of the cross-linked cells measured at 30, 40
      and 50  degrees C were 4.5-, 5.3-, and 5.1-fold those of the free cells,
      respectively. The concentration of (R)-(-)-mandelic acid reached 280 mM after
      merely 2 h transformation with the immobilized cells using 300 mM mandelonitrile
      as substrate, affording an extremely high productivity of 510.7 g L(-1) d(-1). In
      addition, operational stability of the immobilized cells was obviously superior
      to that of free cells, without significant activity loss after 15 cycles of batch
      reactions or 8 cycles of repeated fed-batch reactions. Therefore, the easy
      preparation and robust characteristics of the immobilized biocatalyst make it a
      very promising biocatalyst for high-performance and low-cost production of
      optically pure (R)-(-)-mandelic acid.

PMID- 24317428
TI  - Immobilization of naringin onto chitosan substrates by using ozone activation.
AB  - Ozone oxidation can easily produce peroxides containing active free radicals that
      can be used for the surface modification of biomaterials. This process is highly
      efficient and nontoxic. In this research, naringin, an HMG-CoA reductase
      inhibitor that can promote bone formation, was immobilized onto a chitosan film
      using ozone activation. First, a chitosan film was treated by ozone to produce
      peroxides; these peroxides were then quantified and their amount was optimized by
      an iodide assay. For the in vitro delivery of naringin, a chitosan-naringin
      substrate was immersed in phosphate-buffered saline to quantify the released
      amount of naringin. It was found that the immobilized naringin was slowly
      released over the course of two weeks, where its concentration in the medium was
      controlled by this delivery process. The results of cell culture showed that cell
      viability and early osteogenic differentiation, as measured by alkaline
      phosphatase expression, were promoted with the immobilized naringin on chitosan
      substrates. The expression of osteogenic proteins, including type-I collagen,
      bone siloprotein, and osteocalcin, were also enhanced. According to the results
      of Smad1 and Smad6 phosphorylation, immobilized naringin on ozonated chitosan
      substrates would be able to initiate bone morphogenetic protein-Smad signaling by
      activating receptor Smad and by suppressing inhibitory Smad. The results in this
      research demonstrated that the naringin-chitosan substrate produced by
      biocompatible ozone activation was highly osteoconductive without cytotoxicity. 

PMID- 24317429
TI  - Identification and quantification of the main active anticancer alkaloids from
      the root of Glaucium flavum.
AB  - Glaucium flavum is used in Algerian folk medicine to remove warts (benign
      tumors). Its local appellations are Cheqiq el-asfar and Qarn el-djedyane. We have
      recently reported the anti-tumoral activity of Glaucium flavum root alkaloid
      extract against human cancer cells, in vitro and in vivo. The principal
      identified alkaloid in the extract was protopine. This study aims to determine
      which component(s) of Glaucium flavum root extract might possess potent antitumor
      activity on human cancer cells. Quantitative estimation of Glaucium flavum
      alkaloids was realized by HPLC-DAD. Glaucium flavum effect on human normal and
      cancer cell viability was determined using WST-1 assay. Quantification of
      alkaloids in Glaucium flavum revealed that the dried root part contained 0.84% of
      protopine and 0.07% of bocconoline (w/w), while the dried aerial part contained
      only 0.08% of protopine, glaucine as the main alkaloid, and no bocconoline. In
      vitro evaluation of the growth inhibitory activity on breast cancer and normal
      cells demonstrated that purified protopine did not reproduce the full cytotoxic
      activity of the alkaloid root extract on cancer cell lines. On the other hand,
      bocconoline inhibited strongly the viability of cancer cells with an IC50 of 7.8
      uM and only a low cytotoxic effect was observed against normal human cells. Our
      results showed for the first time that protopine is the major root alkaloid of
      Glaucium flavum. Finally, we are the first to demonstrate a specific anticancer
      effect of Glaucium flavum root extract against breast cancer cells, which can be
      attributed, at least in part, to bocconoline. 

PMID- 24317430
TI  - Pro-apoptotic effect of rice bran inositol hexaphosphate (IP6) on HT-29
      colorectal cancer cells.
AB  - Inositol hexaphosphate (IP6), or phytic acid is a natural dietary ingredient and
      has been described as a "natural cancer fighter", being an essential component of
      nutritional diets. The marked anti-cancer effect of IP6 has resulted in our quest
      for an understanding of its mechanism of action. In particular, our data provided
      strong evidence for the induction of apoptotic cell death, which may be
      attributable to the up-regulation of Bax and down-regulation of Bcl-xl in favor
      of apoptosis. In addition, the up-regulation of caspase-3 and -8 expression and
      activation of both caspases may also contribute to the apoptotic cell death of
      human colorectal adenocarcinoma HT-29 cells when exposed to IP6. Collectively,
      this present study has shown that rice bran IP6 induces apoptosis, by regulating
      the pro- and anti-apoptotic markers; Bax and Bcl-xl and via the activation of
      caspase molecules (caspase-3 and -8). 

PMID- 24317431
TI  - Evaluation of individual and combined applications of serum biomarkers for
      diagnosis of hepatocellular carcinoma: a meta-analysis.
AB  - The clinical value of Serum alpha-fetoprotein (AFP) to detect early
      hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and
      specificity found in recent years. Other than AFP, several new serum biomarkers
      including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP)
      and Golgi protein-73 (GP73) have been identified as useful HCC markers. In this
      investigation, we review the current knowledge about these HCC-related
      biomarkers, and sum up the results of our meta-analysis on studies that have
      addressed the utility of these biomarkers in early detection and prognostic
      prediction of HCC. A systematic search in PubMed, Web of Science, and the
      Cochrane Library was performed for articles published in English from 1999 to
      2012, focusing on serum biomarkers for HCC detection. Data on sensitivity and
      specificity of tests were extracted from 40 articles that met the inclusion
      criteria, and the summary receiver operating characteristic curve (sROC) was
      obtained. A meta-analysis was carried out in which the area under the curve (AUC)
      for each biomarker or biomarker combinations (AFP, DCP, GP73, AFP-L3, AFP+DCP,
      AFP+AFP-L3, and AFP+GP73) was used to compare the diagnostic accuracy of
      different biomarker tests. The AUC of AFP, DCP, GP73, AFP-L3, AFP+DCP, AFP+AFP
      L3, and AFP+GP73 are 0.835, 0.797, 0.914, 0.710, 0.874, 0.748, and 0.932
      respectively. A combination of AFP+GP73 is superior to AFP in detecting HCC and
      differentiating HCC patients from non-HCC patients, and may prove to be a useful
      marker in the diagnosis and screening of HCC. In addition, the AUC of GP73,
      AFP+DCP and AFP+GP73 are better than that of AFP. The clinical value of GP73,
      AFP+DCP, or AFP+GP73 as serological markers for HCC diagnosis needs to be
      addressed further in future studies.

PMID- 24317432
TI  - Mutation in the pssA gene involved in exopolysaccharide synthesis leads to
      several physiological and symbiotic defects in Rhizobium leguminosarum bv.
      trifolii.
AB  - The symbiotic nitrogen-fixing bacterium Rhizobium leguminosarum bv. trifolii 24.2
      secretes large amounts of acidic exopolysaccharide (EPS), which plays a crucial
      role in establishment of effective symbiosis with clover. The biosynthesis of
      this heteropolymer is conducted by a multi-enzymatic complex located in the
      bacterial inner membrane. PssA protein, responsible for the addition of glucose-1
      phosphate to a polyprenyl phosphate carrier, is involved in the first step of EPS
      synthesis. In this work, we characterize R. leguminosarum bv. trifolii strain
      Rt270 containing a mini-Tn5 transposon insertion located in the 3'-end of the
      pssA gene. It has been established that a mutation in this gene causes a
      pleiotropic effect in rhizobial cells. This is confirmed by the phenotype of the
      mutant strain Rt270, which exhibits several physiological and symbiotic defects
      such as a deficiency in EPS synthesis, decreased motility and utilization of some
      nutrients, decreased sensitivity to several antibiotics, an altered extracellular
      protein profile, and failed host plant infection. The data of this study indicate
      that the protein product of the pssA gene is not only involved in EPS synthesis,
      but also required for proper functioning of Rhizobium leguminosarum bv. trifolii
      cells. 

PMID- 24317433
TI  - Citrange fruit extracts alleviate obesity-associated metabolic disorder in high
      fat diet-induced obese C57BL/6 mouse.
AB  - Obesity is becoming one of the global epidemics of the 21st century. In this
      study, the effects of citrange (Citrus sinensis * Poncirus trifoliata) fruit
      extracts in high-fat (HF) diet-induced obesity mice were studied. Female C57BL/6
      mice were fed respectively a chow diet (control), an HF diet, HF diet
      supplemented with 1% w/w citrange peel extract (CPE) or 1% w/w citrange flesh and
      seed extract (CFSE) for 8 weeks. Our results showed that both CPE and CFSE
      regulated the glucose metabolic disorders of obese mice. In CPE and CFSE-treated
      groups, the body weight gain, blood glucose, serum total cholesterol (TC) and low
      density lipoprotein cholesterol (LDL-c) levels were significantly (p<0.05)
      reduced relative to those in the HF group. To explore the mechanisms of action of
      CPE and CFSE on the metabolism of glucose and lipid, related genes' expressions
      in liver were assayed. In liver tissue, the expression level of peroxisome
      proliferator-activated receptor gamma (PPARgamma) and its target genes were down
      regulated by CPE and CFSE supplementation as revealed by qPCR tests. In addition,
      both CPE and CFSE decreased the expression level of liver X receptor (LXR) alpha
      and beta, which are involved in lipid and glucose metabolism. Taken together,
      these results suggest that CPE and CFSE administration could ameliorate obesity
      and related metabolic disorders in HF diet-induced obesity mice probably through
      the inhibition of PPARgamma and LXRs gene expressions.

PMID- 24317434
TI  - Antiepileptic potential of matrine via regulation the levels of gamma
      aminobutyric acid and glutamic acid in the brain.
AB  - Our present study aimed to determine the antiepileptic activity of matrine, and
      explore the possible molecular mechanism. To evaluate the antiepileptic activity
      of matrine, seizures in mice induced by PTZ and MES were established, then the
      pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in
      mice were also carried out. For the molecular mechanism investigations, contents
      of aspartic acid (Asp), gamma-aminobutyric acid (GABA), glutamic acid (Glu),
      glycine (Gly) in seizures mice were determined; then, the chronic seizures rats
      induced by PTZ were prepared, and western blotting was used to determine the
      expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine
      showed significant antiepileptic effects on seizures mice induced by MES and PTZ.
      Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor
      activity tests were also demonstrated that matrine had obvious antiepileptic
      effects. Additionally, our results revealed that after treatment with matrine,
      contents of GABA can be elevated, and the contents of Glu were obviously
      decreased. Furthermore, western blotting revealed that the mechanism regarding
      the antiepileptic effect of may be related to the up-regulations of GAD 65 and
      GABAA in the brain. Collectively, we suggested that matrine can be developed as
      an effective antiseptic drug. 

PMID- 24317435
TI  - Tandem aldol-Michael reactions in aqueous diethylamine medium: a greener and
      efficient approach to bis-pyrimidine derivatives.
AB  - A simple protocol, involving the green synthesis for the construction of novel
      bis-pyrimidine derivatives, 3a-i and 4a-e are accomplished by the aqueous
      diethylamine media promoted tandem Aldol-Michael reaction between two molecules
      of barbituric acid derivatives 1a,b with various aldehydes. This efficient
      synthetic protocol using an economic and environmentally friendly reaction media
      with versatility and shorter reaction time provides bis-pyrimidine derivatives
      with high yields (88%-99%). 

PMID- 24317437
TI  - The lack of cytotoxic effect and radioadaptive response in splenocytes of mice
      exposed to low level internal beta-particle irradiation through tritiated
      drinking water in vivo.
AB  - Health effects of tritium, a beta-emitter and a by-product of the nuclear
      industry, is a subject of significant controversy. This mouse in vivo study was
      undertaken to monitor biological effects of low level tritium exposure. Mice were
      exposed to tritiated drinking water (HTO) at 10 KBq/L, 1 MBq/L and 20 MBq/L
      concentrations for one month. The treatment did not result in a significant
      increase of apoptosis in splenocytes. To examine if this low level tritium
      exposure alters radiosensitivity, the extracted splenocytes were challenged in
      vitro with 2 Gy gamma-radiation, and apoptotic responses at 1 and 24 h were
      measured. No alterations in the radiosensitivity were detected in cells from mice
      exposed to tritium compared to sham-treated mice. In contrast, low dose gamma
      irradiation at 20 or 100 mGy, resulted in a significant increase in resistance to
      apoptotic cell death after 2 Gy irradiation; an indication of the radioadaptive
      response. Overall, our data suggest that low concentrations of tritium given to
      mice as HTO in drinking water do not exert cytotoxic effect in splenocytes, nor
      do they change cellular sensitivity to additional high dose gamma-radiation. The
      latter may be considered as the lack of a radioadaptive response, typically
      observed after low dose gamma-irradiation. 

PMID- 24317436
TI  - The dual role of Smad7 in the control of cancer growth and metastasis.
AB  - Smad7 was initially identified as an inhibitor of Transforming growth factor
      (TGF)-beta due mainly to its ability to bind TGF-beta receptor type I and prevent
      TGF-beta-associated Smad signaling. More recently, it has been demonstrated that
      Smad7 can interact with other intracellular proteins and regulate also TGF-beta
      independent signaling pathways thus making a valid contribution to the neoplastic
      processes in various organs. In particular, data emerging from experimental
      studies indicate that Smad7 may differently modulate the course of various tumors
      depending on the context analyzed. These observations, together with the
      demonstration that Smad7 expression is deregulated in many cancers, suggest that
      therapeutic interventions around Smad7 can help interfere with the
      development/progression of human cancers. In this article we review and discuss
      the available data supporting the role of Smad7 in the modulation of cancer
      growth and progression. 

PMID- 24317439
TI  - The HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) synergizes
      with cisplatin and induces apoptosis in cisplatin-resistant esophageal squamous
      cell carcinoma cell lines via the Akt/XIAP pathway.
AB  - Although cisplatin (CDDP) is a key drug in the treatment of esophageal squamous
      cell carcinoma (ESCC), acquired chemoresistance remains a major problem.
      Combination therapy may represent one strategy to overcome this resistance. Heat
      shock protein 90 (HSP90) is known to be overexpressed in several types of cancer
      cells, and its inhibition by small molecules, either alone or in combination, has
      shown promise in the treatment of solid malignancies. In the present study, we
      evaluated the synergistic effects of combining CDDP with the HSP90 inhibitor 17-N
      allylamino-17-demethoxy geldanamycin (17-AAG) on two CDDP-resistant human
      esophageal squamous cancer cell lines, KYSE30 and KYSE150. The results obtained
      demonstrated the synergistic inhibitory effects of CDDP and 17-AAG on the growth
      of KYSE30 and KYSE150 cells. Cell growth and cell number were more effectively
      reduced by the combined treatment with CDDP and 17-AAG than by the treatment with
      either CDDP or 17-AAG alone. Western blotting revealed that the combined action
      of CDDP and 17-AAG cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3,
      which demonstrated that the reduction in both cell growth and cell number was
      mediated by apoptosis. Time-course experiments showed that reduction in X-linked
      inhibitor of apoptosis protein (XIAP) and phosphorylated Akt were concomitant
      with apoptosis. The results of the present study demonstrate that 17-AAG
      synergizes with CDDP and induces apoptosis in CDDP-resistant ESCC cell lines, and
      also that modulation of the Akt/XIAP pathway may underlie this synergistic
      effect. Combination therapy with CDDP and an HSP90 inhibitor may represent a
      promising strategy to overcome CDDP resistance in ESCC. 

PMID- 24317440
TI  - A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits
      gastric cancer cell growth.
AB  - Retinoic acid (RA) analogs have been used in the treatment of a variety of
      cancers; however, their application is limited due to serious therapy-related
      sequelae. In the present study, the effects of a novel RA analog, 4-amino-2
      trifluoromethyl-phenyl retinate (ATPR), on the growth of gastric cancer cells
      were evaluated. Three gastric cancer cell lines, AGS, MKN-74 and SC-M1, were
      treated with either all-trans retinoic acid (ATRA) or ATPR, and their growth and
      distribution in different cell cycle phases were assessed using an MTT assay and
      propidium iodide (PI) staining followed by flow cytometry. The binding affinity
      of ATPR to the retinoic acid receptors, retinoic acid receptor-alpha (RAR-alpha)
      and retinoid X receptor-alpha (RXR-alpha), was determined using ligand-binding
      assays. Activator protein-1 (AP-1) activity was measured using a luciferase
      reporter assay. Western blot analysis was used to determine cyclin E, Bcl-2 and
      Bax protein expression. ATPR preferentially bound RXR-alpha (0.04 nM) as compared
      with RAR-alpha (20.96 nM). Although both ATRA and ATPR inhibited the growth of
      AGS, MKN-74 and SC-M1 cells in a dose-dependent manner, a significantly greater
      inhibitory effect was observed with treatment with 5 and 500 uM ATPR for 3 days
      (P<0.05). In addition, ATPR (50 uM), but not ATRA, significantly increased the
      population of AGS and MKN-74 cells in the subG1 phase and decreased the Bcl-2/Bax
      ratio (P<0.05). Furthermore, in MNK-74 and SC-M1 cells treated with 12-O
      tetradecanoylphorbol-13-acetate (TPA) and 5 or 10 uM of ATPR significantly
      suppressed the activity of the AP-1 reporter as compared to treatment with ATRA
      (P<0.05). Thus, ATPR inhibits cancer cell proliferation to a greater extent
      compared to ATRA, possibly through the RXR-mediated inhibition of AP-1 activity.

PMID- 24317438
TI  - A novel adaptation of laparoscopic Tenckhoff catheter insertion technique to
      enhance catheter stability and function in automated peritoneal dialysis.
AB  - INTRODUCTION: Automated peritoneal dialysis (APD) normally takes place overnight.
      Maintaining a stable PD catheter position, independent of body position, omental
      wrapping or catheter displacement secondary to bowel movements is essential in
      maintaining effective catheter function. METHODS: We developed a new procedure of
      catheter placement through combining and adapting several previously described
      operative techniques including laparoscopic placement of a curled double cuff
      Tenckhoff catheter with subcutaneous tunneling superior to the rectus sheet, an
      oblique course through the abdominal wall, deep entry into the pelvic peritoneum
      and directed placement of the curled tip within the pouch of Douglas.
      Retrospective analysis of catheter function was conducted, evaluating catheter
      position, function, complication rate and catheter survival against findings for
      current insertion techniques described within literature. RESULTS: Between March
      2009 and November 2011, 54 patients underwent PD catheter insertion. The
      observation period was an average of 343 +/- 273 days. All patients received
      abdominal plain film showing optimal catheter position in 89 %. Reported catheter
      function was very good in 85.2 %, with no or few alarms per week during APD,
      moderate in 9.3 % with occasional minor dysfunctions (<= 2 alarms per night), and
      poor in 5.6 %, with regular alarm disturbance. In one case, primary dysfunction
      led to catheter replacement. At completion, stable catheter function with
      occasional minor dysfunction was achieved in 52 of 54 cases. Catheter-related
      complications (leakage, hydrocele formation, infection and need for replacement)
      were observed in 14.8 %. At the end of the observation period, 55.6 % of
      catheters remained in use. Patient dropout occurred through death (18.5 %), renal
      transplantation (7.4 %), renal recovery (1.9 %), removal secondary to infection
      or dysfunction (9.3 %) and conversion to HD due to poor dialysis quality (7.4 %).
      CONCLUSION: The above technique combines and optimises previously described
      laparoscopic catheter implantation techniques, allowing increased catheter
      stability resulting in an undisturbed catheter function suitable for APD.

PMID- 24317441
TI  - An electronic specimen collection protocol schema (eSCPS). Document architecture
      for specimen management and the exchange of specimen collection protocols between
      biobanking information systems.
AB  - BACKGROUND: The integrity of collection protocols in biobanking is essential for
      a high-quality sample preparation process. However, there is not currently a well
      defined universal method for integrating collection protocols in the biobanking
      information system (BIMS). Therefore, an electronic schema of the collection
      protocol that is based on Extensible Markup Language (XML) is required to
      maintain the integrity and enable the exchange of collection protocols. MATERIALS
      AND METHODS: The development and implementation of an electronic specimen
      collection protocol schema (eSCPS) was performed at two institutions (Muenster
      and Cologne) in three stages. First, we analyzed the infrastructure that was
      already established at both the biorepository and the hospital information
      systems of these institutions and determined the requirements for the sufficient
      preparation of specimens and documentation. Second, we designed an eSCPS
      according to these requirements. Finally, a prospective study was conducted to
      implement and evaluate the novel schema in the current BIMS. RESULTS: We designed
      an eSCPS that provides all of the relevant information about collection
      protocols. Ten electronic collection protocols were generated using the
      supplementary Protocol Editor tool, and these protocols were successfully
      implemented in the existing BIMS. Moreover, an electronic list of collection
      protocols for the current studies being performed at each institution was
      included, new collection protocols were added, and the existing protocols were
      redesigned to be modifiable. The documentation time was significantly reduced
      after implementing the eSCPS (5 +/- 2 min vs. 7 +/- 3 min; p = 0.0002).
      CONCLUSION: The eSCPS improves the integrity and facilitates the exchange of
      specimen collection protocols in the existing open-source BIMS.

PMID- 24317442
TI  - The alpha-7 nicotinic receptor partial agonist/5-HT3 antagonist RG3487 enhances
      cortical and hippocampal dopamine and acetylcholine release.
AB  - RATIONALE: Alpha-7 nicotinic acetylcholine receptor (nAChR) agonists may
      ameliorate cognitive deficits in schizophrenia, in part, because of their ability
      to enhance dopaminergic and cholinergic neurotransmission. OBJECTIVES: In the
      current study, the effects of partial nAChR agonist and 5-HT3 receptor antagonist
      RG3487 (previously R3487/MEM3454) on dopamine (DA) and acetylcholine (ACh)
      effluxes in rat prefrontal cortex (mPFC) and hippocampus (HIP) were investigated
      in awake, freely moving rats. RESULTS: R3487/MEM3454, at doses of 0.1-10 mg/kg,
      s.c., enhanced DA and ACh effluxes in rat mPFC and (HIP), with a peak effect at
      0.3- to 0.6-mg/kg doses, producing a bell-shaped dose-response curve.
      Pretreatment with the selective nAChR antagonist, methyllycaconitine (1.0 mg/kg),
      completely blocked RG3487-induced (0.45 mg/kg) DA but not ACh efflux, while the
      selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (1.0 mg/kg)
      partially inhibited cortical ACh but not DA efflux. RG3487 (0.45 mg/kg) combined
      with atypical antipsychotic drug (APD) risperidone (0.1 mg/kg), but not typical
      APD haloperidol (0.1 mg/kg), induced a significantly greater increase in HIP ACh
      efflux. Their combined effect on DA efflux was additive. RG3487, combined with
      other atypical APDs, namely aripiprazole (0.3 mg/kg), olanzapine (1.0 mg/kg), and
      quetiapine (30 mg/kg), also produced additive effects on DA efflux. CONCLUSIONS:
      These results suggest that RG3487 enhances DA efflux by nAChR stimulation,
      whereas ACh efflux is primarily mediated via 5-HT3 receptor antagonism, and that
      RG3487 alone or as augmentation may improve cognitive impairment in
      schizophrenia.

PMID- 24317443
TI  - The effects of nicotine exposure during Pavlovian conditioning in rats on several
      measures of incentive motivation for a conditioned stimulus paired with water.
AB  - RATIONALE: Nicotine enhances approach toward and operant responding for
      conditioned stimuli (CSs), but the effect of exposure during different phases of
      Pavlovian incentive learning on these measures remains to be determined.
      OBJECTIVES: These studies examined the effects of administering nicotine early,
      late or throughout Pavlovian conditioning trials on discriminated approach
      behavior, nicotine-enhanced responding for conditioned reinforcement, extinction,
      and the reinstatement of responding for conditioned reinforcement. We also tested
      the effect of nicotine on approach to a lever-CS in a Pavlovian autoshaping
      procedure and for this CS to serve as a conditioned reinforcer. METHODS: Thirsty
      rats were exposed to 13 conditioning sessions where a light/tone CS was paired
      with the delivery of water. Nicotine was administered either prior to the first
      or last seven sessions, or throughout the entire conditioning procedure.
      Responding for conditioned reinforcement, extinction, and the reinstatement of
      responding by the stimulus and nicotine were compared across exposure groups.
      Separately, the effects of nicotine on conditioned approach toward a lever-CS
      during autoshaping, and responding for that CS as a conditioned reinforcer, were
      examined. RESULTS: Nicotine exposure was necessary for nicotine-enhanced
      responding for conditioned reinforcement and the ability for nicotine and the
      stimulus to additively reinstate responding on the reinforced lever. Nicotine
      increased contacts with a lever-CS during autoshaping, and removal of nicotine
      abolished this effect. Prior nicotine exposure was necessary for nicotine
      enhanced responding reinforced by the lever. CONCLUSIONS: Enhancements in the
      motivating properties of CSs by nicotine occur independently from duration and
      timing effects of nicotine exposure during conditioning.

PMID- 24317444
TI  - Higher long-lasting ethanol sensitization after adolescent ethanol exposure in
      mice.
AB  - RATIONALE: Due to their maturing brain, adolescents are suggested to be more
      vulnerable to the long-term consequences of chronic alcohol use. Increased
      sensitization to the stimulant effects of ethanol is a possible consequence of
      ethanol exposure during adolescence. OBJECTIVES: The aim of this study was to
      characterize the long-term alterations in the stimulant effects of ethanol and in
      the rate of ethanol sensitization in mice pre-exposed to ethanol during
      adolescence in comparison to mice pre-exposed to ethanol in adulthood. METHODS:
      Adolescent and adult female Swiss mice were injected with saline or ethanol (2.5
      or 4 g/kg) during 14 consecutive days. After a 3-week period of ethanol
      abstinence, mice were tested as adults before and after a second exposure to
      daily repeated ethanol injections. RESULTS: All mice pre-exposed to ethanol as
      adults or adolescents showed higher stimulant effects when re-exposed to ethanol
      3 weeks later. However, this enhanced sensitivity to the stimulant effects of
      ethanol was of significantly higher magnitude in mice repeatedly injected with
      high ethanol doses (4 g/kg) during adolescence. Furthermore, the increased
      expression of ethanol stimulant effects in these mice was maintained even after a
      second procedure of ethanol sensitization. CONCLUSIONS: Adolescence is a critical
      period for the development of a sensitization to ethanol stimulant properties
      providing that high intermittent ethanol doses are administered. These results
      might contribute to explain the relationship between age at first alcohol use and
      risks of later alcohol problems and highlight the dangers of repeated consumption
      of high alcohol amounts in young adolescents.

PMID- 24317445
TI  - Modulation of the human rho1 GABAA receptor by inhibitory steroids.
AB  - RATIONALE: Modulators of the rho1 GABAA receptor may be useful in the treatment
      of visual, sleep, and cognitive disorders. Neuroactive steroids and analogues
      have been shown to modulate rho1 receptor function, but the molecular mechanisms
      are poorly understood. OBJECTIVES: We employed electrophysiology and voltage
      clamp fluorometry to compare the actions of several neuroactive steroids and
      analogues on the human rho1 GABAA receptor. RESULTS: Results confirmed that P294S
      and T298F mutations affect modulation by steroids. The P294S mutation abolished
      inhibition by (3alpha,5beta)-3-hydroxypregnan-20-one (3alpha5betaP) while the
      T298F mutation eliminated inhibition by 17beta-estradiol. Voltage-clamp
      fluorometry demonstrated that steroids differing in the presence of a charged
      group on C3 or nature of substituent on C17 uniquely modified fluorescence
      changes elicited by GABA in the extracellular domain. The I307Q mutation reversed
      the inhibitory effect of 3alpha5betaP but was without effect on modulation by
      (3alpha,5beta)-3-hydroxypregnan-20-one sulfate or 17beta-estradiol. The effect of
      3alpha5betaP on the fluorescence change generated at Y241C was dependent on
      whether the steroid acted as an inhibitor or a potentiator. Further, the effect
      was limited to uncharged 5beta-reduced steroids containing an acetyl group on
      C17. CONCLUSIONS: The data demonstrate that steroids and analogues differ with
      respect to conformational changes elicited by these drugs as well as sensitivity
      to the effects of mutations. Steroids and analogues could be provisionally
      divided into three major groups based on their actions on the rho1 GABAA
      receptor: 5beta-reduced uncharged steroids, sulfated and carboxylated steroids,
      and 17beta-estradiol. Further division among 5beta-reduced uncharged steroids was
      based on substituent at position C17.

PMID- 24317448
TI  - BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation
      dependent activation of HAUSP.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by
      the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor
      suppressor phosphatase and tensin homolog (PTEN) has recently been shown to have
      a critical role in the pathogenesis of CML. Nuclear localization and proper
      nuclear-cytoplasmic shuttling are crucial for PTEN's tumor suppressive function.
      In this study, we show that BCR-ABL enhances HAUSP-induced de-ubiquitination of
      PTEN in turn favoring its nuclear exclusion. We further demonstrate that BCR-ABL
      physically interacts with and phosphorylates HAUSP on tyrosine residues to
      trigger its activity. Importantly, we also find that PTEN delocalization induced
      by BCR-ABL does not occur in the leukemic stem cell compartment due to high
      levels of PML, a potent inhibitor of HAUSP activity toward PTEN. We therefore
      identify a new proto-oncogenic mechanism whereby BCR-ABL antagonizes the nuclear
      function of the PTEN tumor suppressor, with important therapeutic implications
      for the eradication of CML minimal residual disease. 

PMID- 24317449
TI  - Implications of the World Trade Center Health Program (WTCHP) for the public
      health response to the Great East Japan Earthquake.
AB  - The attacks on the World Trade Center (WTC) on September 11, 2001 resulted in a
      serious burden of physical and mental illness for the 50,000 rescue workers that
      responded to 9/11 as well as the 400,000 residents and workers in the surrounding
      areas of New York City. The Zadroga Act of 2010 established the WTC Health
      Program (WTCHP) to provide monitoring and treatment of WTC exposure-related
      conditions and health surveillance for the responder and survivor populations.
      Several reports have highlighted the applicability of insights gained from the
      WTCHP to the public health response to the Great East Japan Earthquake. Optimal
      exposure monitoring processes and attention to the welfare of vulnerable exposed
      sub-groups are critical aspects of the response to both incidents. The ongoing
      mental health care concerns of 9/11 patients accentuate the need for accessible
      and appropriately skilled mental health care in Fukushima. Active efforts to
      demonstrate transparency and to promote community involvement in the public
      health response will be highly important in establishing successful long-term
      monitoring and treatment programs for the exposed populations in Fukushima. 

PMID- 24317451
TI  - A dual-plate ITO-ITO generator-collector microtrench sensor: surface activation,
      spatial separation and suppression of irreversible oxygen and ascorbate
      interference.
AB  - Generator-collector electrode systems are based on two independent working
      electrodes with overlapping diffusion fields where chemically reversible redox
      processes (oxidation and reduction) are coupled to give amplified current
      signals. A generator-collector trench electrode system prepared from two tin
      doped indium oxide (ITO) electrodes placed vis-a-vis with a 22 MUm inter
      electrode gap is employed here as a sensor in aqueous media. The reversible 2
      electron anthraquinone-2-sulfonate redox system is demonstrated to give well
      defined collector responses even in the presence of oxygen due to the
      irreversible nature of the oxygen reduction. For the oxidation of dopamine on
      ITO, novel "Piranha-activation" effects are observed and chemically reversible
      generator-collector feedback conditions are achieved at pH 7, by selecting a more
      negative collector potential, again eliminating possible oxygen interference.
      Finally, dopamine oxidation in the presence of ascorbate is demonstrated with the
      irreversible oxidation of ascorbate at the "mouth" of the trench electrode and
      chemically reversible oxidation of dopamine in the trench "interior". This
      spatial separation of chemically reversible and irreversible processes within and
      outside the trench is discussed as a potential in situ microscale sensing and
      separation tool. 

PMID- 24317450
TI  - Obstructive sleep apnea in North American commercial drivers.
AB  - The most common medical cause of excessive daytime sleepiness (EDS) is
      obstructive sleep apnea (OSA). Specifically, among an estimated 14 million US
      commercial drivers, 17-28% or 2.4 to 3.9 million are expected to have OSA. Based
      on existing epidemiologic evidence, most of these drivers are undiagnosed and not
      adequately treated. Untreated OSA increases the risk of vehicular crashes as
      documented in multiple independent studies and by meta-analysis. Therefore,
      identifying commercial drivers with OSA and having them effectively treated
      should decrease crash-related fatalities and injuries. Several strategies are
      available for screening and identifying drivers with OSA. The simplest and most
      effective objective strategies use body mass index (BMI) cutoffs for obesity.
      Functional screens are promising adjuncts to other objective tests. The most
      effective approach will likely be a combination of a good questionnaire; BMI
      measures; and a careful physician-obtained history complemented by a functional
      screen. 

PMID- 24317452
TI  - Hypokalemic hypertension related to clozapine: a case report.

PMID- 24317453
TI  - The effects of venlafaxine on cortical motor area activity in healthy subjects: a
      pilot study.
AB  - In the study, we used functional magnetic resonance imaging associated with
      behavioral assessment to observe the effects of venlafaxine on the modulation of
      human motor cortex activation and to provide preliminary data for further
      assessing its influence on motor functional reorganization after stroke injury.
      In a randomized, double-blind, crossover study, 8 right-handed subjects received
      75 mg of either venlafaxine or a placebo daily over a period of 7 days separated
      by 3 washout days. The volunteers were asked to execute motor tasks, which
      included the dynamometer and finger-tapping test. In addition, laboratory tests
      and functional magnetic resonance imaging examination, before the start of the
      experiment and after administration of placebo and venlafaxine, were performed.
      It was shown that the finger-tapping rate of each hand in the venlafaxine stage
      was significantly improved compared with that observed in the placebo stage (n =
      8, F left hand = 57.69, F right hand = 184.48, P < 0.001). The changes in the
      recorded grip strengths of both hands were not significant between the stages (n
      = 8, F = 2.63, P > 0.05). In the venlafaxine stage, the activations of the
      contralateral primary sensorimotor cortex, contralateral premotor cortex, and
      contralateral supplementary motor area were enhanced significantly, whereas the
      activation of the bilateral parietal cortices was decreased when compared with
      the placebo stage. Meanwhile, the enhancement of contralateral primary
      sensorimotor cortex activation had a positive correlation with the improvement of
      the finger-tapping rate. It was concluded that venlafaxine could modulate the
      cortical excitability and improve finger dexterity and reaction speed, which
      greatly related to the increase of contralateral motor cortical excitability.

PMID- 24317454
TI  - Results and prospects of chromosomal gene transfer between cultured mammalian
      cells.

PMID- 24317455
TI  - Long term selection for four-week body weight in Japanese quail under different
      nutritional environments.
AB  - Individual phenotypic selection for high 4 week body weight was conducted for 40
      generations in two lines of Japanese quail under two protein environments. Line P
      was selected on an adequate 28% protein diet, and line T was selected on a 20%
      protein diet containing 0.2% thiouracil (TU). In generation 20, a subline R was
      established by subjecting progeny from the T line to a 20% protein diet; in
      generation 27, a subline S was developed by subjecting progeny from the T line to
      a 28% protein diet containing 0.2% TU. Progeny from a nonselected control line
      (C) were reared with selected lines and sublines in all generations.Quail in the
      P line continued to respond to selection for 40 generations; body weights
      increased from 90 to approximately 200 g. Mean body weights of T line quail
      peaked in generation 22 and did not appear to show any definite gains thereafter.
      Body weight responses of sublines R and S were greater than those in the T line
      and indicate that changing the selection environment following long-term
      selection may be an effective technique to maximize total selection responses for
      4-week body weight in quail. Realized heritability estimates for 4-week body
      weight were larger in the P line than in the T line in all comparisons. Realized
      estimates were high (30-45%) for the ten generations 1-10; moderate (15-20%) for
      generations 11-30, and small (5-10%) for generations 31-40. 

PMID- 24317456
TI  - Effect of hexane and humidity on self-incompatibility in Brassica oleracea.
AB  - The effects of hexane, high humidity, flower age and temperature in overcoming
      the self-incompatibility of Brassica oleracea were studied using three plants,
      each of which was homozygous for a different dominant S-allele. Hexane had a
      significant effect in all cases, but the size of the effect varied considerably.
      In one plant there was a marked interaction between the effect of hexane,
      humidity and flower age, but temperature had relatively little effect. In another
      plant high humidity alone gave a very much greater response than hexane alone.
      This plant gave as many self-seeds from the high humidity treatment as from bud
      selfing, indicating that the incompatibility reaction was almost completely
      overcome by the high humidity. The results are discussed in the light of current
      views of the mechanism of incompatibility in Brassica. 

PMID- 24317457
TI  - The influence and possible recombination of genotypes on the production of
      microspore embryoids in anther cultures of Solanum tuberosum and dihaploid
      hybrids.
AB  - In addition to physical and chemical factors, genotype appears to be a very
      important factor influencing success in anther culture. Recombination by making
      crosses with selected responding clones has been introduced as a possible helpful
      method to positively influence the success and response type via the factor
      genotype. From the progeny of such a cross, one genotype could be selected,
      producing in 30 to 40 percent of the cultured anthers, fully developed embryoids
      and plantlets, which are a mixture of polyploids, dihaploids and
      monohaploids.Further, a pleiotropic marker 'embryo spot' visible as a 'nodal
      band' in the plant stage, has been used to confirm the microsporic origin of
      dihaploids and polyploids and to prove their homozygous nature. This marker also
      shows potential use in confirming the origin of calli from individual
      microspores. 

PMID- 24317458
TI  - An altered chloroplast ribosomal protein in a streptomycin resistant tobacco
      mutant.
AB  - Ribosomal proteins from chloroplasts of Nicotiana tabacum L. (cv. Petit Havana)
      and of SRl, a mutant derived from it, with uniparentally inherited streptomycin
      resistance, were characterised by two-dimensional gel electrophoresis. From the
      67 proteins identified, one has an altered electrophoretic mobility when isolated
      from the mutant. Streptomycin resistance of the SRl mutant therefore seems to be
      the consequence of a mutation in the chloroplast DNA coding for a chloroplast
      ribosomal protein. 

PMID- 24317459
TI  - A non-destructive selection criterion for fibre content in jute : III. the
      criterion and its prospects.
AB  - A new prediction formula using a geometrical description of the jute plant is
      proposed and was found to predict the single plant fibre yield to a remarkable
      degree of accuracy. After an incisive evaluation of 20 component characters,
      plant height, basal and mid-diameters, basal and mid-sample fibre densities were
      selected to formulate the non-destructive prediction criterion. Its superiority
      was upheld when tested in five environments extending over a period of three
      years, 110 genetically distinct entries and 3080 single plants. The prospects of
      this criterion in reorienting the existing breeding technology and devising new
      ones are discussed. 

PMID- 24317460
TI  - Rapid estimation of potato tuber total protein content with coomassie brilliant
      blue G-250.
AB  - A new method for measuring protein with Coo-massie Brilliant Blue G-250 has been
      adapted for use as a screening method in a potato tuber protein improvement
      breeding program. The method is simple, fast and inexpensive, and has
      successfully estimated the total protein content of a broad range of tuber
      genotypes having dissimilar amino acid profiles and tuber maturities. Correlation
      between the Coomassie method and a modified micro-Kjeldahl method, the standard
      method used in the potato breeding program, was 0.93. Free amino acids and other
      compounds which interfere with other methods for measuring protein do not
      interfere with the Coomassie Brilliant Blue procedure. 

PMID- 24317462
TI  - Manipulating the optical properties of symmetrically branched Au/Pd nanocrystals
      through interior design.
AB  - Au/Pd octopods with hollow, cubic interiors and Oh symmetry were synthesized for
      the first time by etching core@shell Pd@Au/Pd octopods to selectively remove
      their Pd interiors. Integration of multiple architectural features - in this case
      branching symmetry, composition, and interior design - into one nanostructure
      provides design strategies to new plasmonic colloids. 

PMID- 24317461
TI  - Improved differentiation between MS and vascular brain lesions using FLAIR* at 7
      Tesla.
AB  - OBJECTIVES: To investigate whether a new magnetic resonance image (MRI) technique
      called T2*-weighted fluid attenuation inversion recovery (FLAIR*) can
      differentiate between multiple sclerosis (MS) and vascular brain lesions, at 7
      Tesla (T). METHODS: We examined 16 MS patients and 16 age-matched patients with
      (risk factors for) vascular disease. 3D-FLAIR and T2*-weighted images were
      combined into FLAIR* images. Lesion type and intensity, perivascular orientation
      and presence of a hypointense rim were analysed. RESULTS: In total, 433 cerebral
      lesions were detected in MS patients versus 86 lesions in vascular patients.
      Lesions in MS patients were significantly more often orientated in a perivascular
      manner: 74 % vs. 47 % (P < 0.001). Ten MS lesions (2.3 %) were surrounded by a
      hypointense rim on FLAIR*, and 24 MS lesions (5.5 %) were hypointense on T2*. No
      lesions in vascular patients showed any rim or hypointensity. Specificity of
      differentiating MS from vascular lesions on 7-T FLAIR* increased when the
      presence of a central vessel was taken into account (from 63 % to 88 %), most
      obviously for deep white matter lesions (from 69 % to 94 %). High sensitivity
      remained (81 %). CONCLUSION: 7-T FLAIR* improves differentiation between MS and
      vascular lesions based on lesion location, perivascular orientation and presence
      of hypointense (rims around) lesions. KEY POINTS: * A new MRI technique T2*
      weighted fluid attenuation inversion recovery (FLAIR*) was investigated. * FLAIR*
      at 7-T MRI combines FLAIR and T2* images into a single image. * FLAIR* at 7 T
      does not require enhancement with contrast agents. *High-resolution 7-T FLAIR*
      improves differentiation between MS and vascular brain lesions. * FLAIR* revealed
      a central vessel more frequently in MS than vascular lesions.

PMID- 24317463
TI  - Characterizing ovarian gene expression during oocyte growth in Atlantic cod
      (Gadus morhua).
AB  - Vertebrate oocytes undergo dramatic changes during development as they accumulate
      many RNA transcripts, glycoproteins, and yolk proteins, necessary to ensure
      proper fertilization and embryogenesis. Oogenesis in teleosts often requires
      several years for completion, but very little is known about the early
      developmental stages. Recently, two-stage gene expression comparisons were made
      during oocyte growth in coho salmon (Oncorhynchus kisutch) and Atlantic cod
      (Gadus morhua), but more broad-scale, comprehensive assessments have not been
      conducted. The objectives of the present study were to characterize the gene
      expression patterns throughout oocyte growth in cod and compare them to changes
      previously identified in coho salmon. A quantitative PCR survey was conducted
      using 50 genes at six ovarian stages, ranging from the onset of primary growth
      (oocyte differentiation) to late vitellogenesis. Most expression patterns could
      be grouped into three major clusters, consisting of oocyte-derived (cluster 1)
      and likely follicle cell (clusters 2 and 3) genes. Oocyte genes were elevated
      during primary growth, while many follicle cell transcripts were abundant during
      oocyte differentiation and vitellogenesis. Few expression changes identified in
      coho salmon were evident in cod, which is likely due to differences in
      reproductive strategies. These results demonstrate that dynamic changes in gene
      expression occur during oocyte growth in teleost fish. 

PMID- 24317464
TI  - A giant spider from the Jurassic of China reveals greater diversity of the
      orbicularian stem group.
AB  - A large female spider, Nephila jurassica, was described from Middle Jurassic
      strata of north-east China and placed in the modern genus Nephila (family
      Nephilidae) on the basis of many morphological similarities, but, as with many
      ancient fossils, the single specimen lacked synapomorphies of the family (Selden
      et al. 2011). In order to test the placement within the nephilid phylogenetic
      tree, Kuntner et al. (2013) calibrated the molecular phylogeny using N. jurassica
      in three different scenarios based on inferred mitochondrial substitution rates.
      They concluded that N. jurassica fitted better as a stem orbicularian than a
      nephilid. Now, a giant male spider has been discovered at the same locality that
      yielded N. jurassica. The two sexes are considered conspecific based on their
      similar morphological features, size, and provenance. The male cannot be
      accommodated in Nephilidae because of its pedipalp morphology, so the new genus
      Mongolarachne and family Mongolarachnidae are erected for the species. Comparison
      with possibly related families show that Mongolarachnidae is most likely on the
      orbicularian stem, close to other cribellate orbicularians (e.g., Deinopoidea),
      which suggests a greater diversity of cribellate orbicularians during the Middle
      Jurassic.

PMID- 24317465
TI  - Technical feasibility of liver transplantation without cold storage.
AB  - PURPOSE: The success of liver transplantation (LT) is accompanied by an increased
      need for organs. The wider use of older donors and marginal organs with risk
      factors such as steatosis has lead to a new interest to improve the outcome with
      marginal organs. We herewith report a novel technique for LT with in situ
      preparation and immediate warm-ischemia liver transplantation (WI-LT). The aim of
      our study was to demonstrate the technical feasibility and report the transplant
      course. METHODS: Six patients underwent WI-LT at our institution. Hepatectomies
      during procurement and LT were both performed in parallel by different surgical
      teams. Technical factors and postoperative allograft function were analyzed.
      RESULTS: All six WI-LTs were performed without intraoperative complications with
      a mean warm-ischemia time (WIT) of 29.0 min. No patient developed primary non
      function or required retransplantation. Mean alanine aminotransferase (194.0 +/-
      170.4 U/l) and aspartate aminotransferase (316.3 +/- 222.1 U/l) values on the
      first postoperative day were low, indicating a low ischemia/reperfusion injury
      and an excellent liver function. CONCLUSIONS: These results demonstrate that WI
      LT is a safe and technically feasible approach for LT with possibly reduced IRI
      and an excellent postoperative allograft quality. WI-LT may therefore be
      considered in individual patients especially with extended criteria donors to
      eventually improve postoperative allograft quality.

PMID- 24317466
TI  - New sinularianin sesquiterpenes from soft coral Sinularia sp.
AB  - Four new sesquiterpenes, sinularianins C-F (3-6), together with known
      sinularianins A (1) and B (2) were identified from a South China Sea soft coral
      Sinularia sp. Compounds 1-6 were evaluated for inhibition of NF-kappaB activation
      using the cell-based HEK293 NF-kappaB luciferase reporter gene assay. Compounds 1
      and 4 were exhibited a potent effect with inhibitory rates of 41.3% and 43.0% at
      the concentration of 10 ug/mL, respectively. 

PMID- 24317467
TI  - Okadaic acid toxin at sublethal dose produced cell proliferation in gastric and
      colon epithelial cell lines.
AB  - The aim of this study was to analyze the effect of Okadaic Acid (OA) on the
      proliferation of gastric and colon epithelial cells, the main target tissues of
      the toxin. We hypothesized that OA, at sublethal doses, activates multiple
      signaling pathways, such as Erk and Akt, through the inhibition of PP2A. To
      demonstrate this, we carried out curves of doses and time response against OA in
      AGS, MKN-45 and Caco 2 cell lines, and found an increase in the cell
      proliferation at sublethal doses, at 24 h or 48 h exposure. Indeed, cells can
      withstand high concentrations of the toxin at 4 h exposure, the time chosen
      considering the maximum time before total gastric emptying. We have proved that
      this increased proliferation is due to an overexpression of Cyclin B, a cyclin
      that promotes the passage from G2 to mitosis. In addition, we have demonstrated
      that OA induces activation of Akt and Erk in the three cells lines, showing that
      OA can activate pathways involved in oncogenesis. In conclusion, this study
      contributes to the knowledge about the possible effects of chronic OA
      consumption. 

PMID- 24317468
TI  - Two novel hepatocellular carcinoma cycle inhibitory cyclodepsipeptides from a
      hydrothermal vent crab-associated fungus Aspergillus clavatus C2WU.
AB  - Two novel cyclodepsipeptides containing an unusual anthranilic acid dimer and a D
      phenyllactic acid residues, clavatustides A and B, were identified from cultured
      mycelia and broth of Aspergillus clavatus C2WU isolated from Xenograpsus
      testudinatus, which lives at extreme, toxic habitat around the sulphur-rich
      hydrothermal vents in Taiwan Kueishantao. This is the first example of
      cyclopeptides containing an anthranilic acid dimer in natural products, and the
      first report of microbial secondary metabolites from the hydrothermal vent crab.
      Clavatustides A and B suppressed the proliferation of hepatocellular carcinoma
      (HCC) cell lines (HepG2, SMMC-7721 and Bel-7402) in a dose-dependent manner, and
      induced an accumulation of HepG2 cells in G1 phase and reduction of cells in S
      phase.

PMID- 24317469
TI  - A new in vitro anti-tumor polypeptide isolated from Arca inflata.
AB  - A new in vitro anti-tumor polypeptide, coded as J2-C3, was isolated from Arca
      inflata Reeve and purified by diethyl-aminoethanol (DEAE)-sepharose Fast Flow
      anion exchange and phenyl sepharose CL-4B hydrophobic chromatography. J2-C3 was
      identified to be a homogeneous compound by native polyacrylamide gel
      electrophoresis (Native-PAGE). The purity of J2-C3 was over 99% in reversed phase
      high performance liquid chromatography (RP-HPLC). The molecular weight was
      determined as 20,538.0 Da by electrospray-ionization mass spectrometry (ESI
      MS/MS). J2-C3 was rich in Glx (Gln + Glu), Lys, and Asx (Asp + Asn) according to
      amino acid analysis. Four partial amino acid sequences of this peptide were
      determined as L/ISMEDVEESR, KNGMHSI/LDVNHDGR, AMKI/LI/LNPKKGI/LVPR and
      AMGAHKPPKGNEL/IGHR via MALDI-TOF/TOF-MS and de novo sequencing. Secondary
      structural analysis by CD spectroscopy revealed that J2-C3 had the alpha-helix
      (45.2%), beta-sheet (2.9%), beta-turn (26.0%) and random coil (25.9%). The anti
      tumor effect of J2-C3 against human tumor cells was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the IC50
      values of J2-C3 were 65.57, 93.33 and 122.95 ug/mL against A549, HT-29 and HepG2
      cell lines, respectively. Therefore, J2-C3 might be developed as a potential anti
      tumor agent.

PMID- 24317470
TI  - Polyhydroxylated steroids from the South China Sea soft coral Sarcophyton sp. and
      their cytotoxic and antiviral activities.
AB  - Chemical investigation on the soft coral Sarcophyton sp. collected from the South
      China Sea yielded three new polyhydroxylated steroids, compounds (1-3), together
      with seven known ones (4-10). Their structures were established by extensive
      spectroscopic methods and comparison of their data with those of the related
      known compounds. All the isolates possessed the 3beta,5alpha,6beta
      trihydroxylated steroidal nucleus. The cytotoxicities against selected HL-60,
      HeLa and K562 tumor cell lines and anti-H1N1 (Influenza A virus (IAV)) activities
      for the isolates were evaluated. Compounds 2, 3 and 5-8 exhibited potent
      activities against K562 cell lines with IC50 values ranging from 6.4 to 10.3 MUM.
      Compounds 1, 6-8 potently inhibited the growth of HL-60 tumor cell lines, and 6
      also showed cytotoxicity towards HeLa cell lines. In addition, preliminary
      structure-activity relationships for the isolates are discussed. The OAc group at
      C-11 is proposed to be an important pharmacophore for their cytotoxicities in the
      3beta,5alpha,6beta-triol steroids. Compounds 4 and 9 exhibited significant anti
      H1N1 IAV activity with IC50 values of 19.6 and 36.7 MUg/mL, respectively.

PMID- 24317472
TI  - HPLC-ESI-IT-MS/MS analysis and biological activity of triterpene glycosides from
      the Colombian marine sponge Ectyoplasia ferox.
AB  - The marine sponge Ectyoplasia ferox produces antipredatory and allelopathic
      triterpenoid glycosides as part of its chemical defense repertoire against
      predators, competitors, and fouling organisms. These molecules are responsible
      for the pharmacological potential found in the glycosides present in this
      species. In order to observe the glycochemical diversity present in E. ferox, a
      liquid chromatography coupled to a tandem mass spectrometry approach to analyse a
      complex polar fraction of this marine sponge was performed. This gave valuable
      information for about twenty-five compounds three of which have been previously
      reported and another three which were found to be composed of known aglycones.
      Furthermore, a group of four urabosides, sharing two uncommon substitutions with
      carboxyl groups at C-4 on the terpenoid core, were identified by a characteristic
      fragmentation pattern. The oxidized aglycones present in this group of saponins
      can promote instability, making the purification process difficult. Cytotoxicity,
      cell cycle modulation, a cell cloning efficiency assay, as well as its hemolytic
      activity were evaluated. The cytotoxic activity was about IC50 40 ug/mL on Jurkat
      and CHO-k1 cell lines without exhibiting hemolysis. Discussion on this
      bioactivity suggests the scanning of other biological models would be worthwhile.

PMID- 24317471
TI  - Exposure to the neurotoxic dinoflagellate, Alexandrium catenella, induces
      apoptosis of the hemocytes of the oyster, Crassostrea gigas.
AB  - This study assessed the apoptotic process occurring in the hemocytes of the
      Pacific oyster, Crassostrea gigas, exposed to Alexandrium catenella, a paralytic
      shellfish toxins (PSTs) producer. Oysters were experimentally exposed during 48 h
      to the toxic algae. PSTs accumulation, the expression of 12 key apoptotic-related
      genes, as well as the variation of the number of hemocytes in apoptosis was
      measured at time intervals during the experiment. Results show a significant
      increase of the number of hemocytes in apoptosis after 29 h of exposure. Two pro
      apoptotic genes (Bax and Bax-like) implicated in the mitochondrial pathway were
      significantly upregulated at 21 h followed by the overexpression of two caspase
      executor genes (caspase-3 and caspase-7) at 29 h, suggesting that the intrinsic
      pathway was activated. No modulation of the expression of genes implicated in the
      cell signaling Fas-Associated protein with Death Domain (FADD) and initiation
      phase (caspase-2) was observed, suggesting that only the extrinsic pathway was
      not activated. Moreover, the clear time-dependent upregulation of five (Bcl2, BI
      1, IAP1, IAP7B and Hsp70) inhibitors of apoptosis-related genes associated with
      the return to the initial number of hemocytes in apoptosis at 48 h of exposure
      suggests the involvement of strong regulatory mechanisms of apoptosis occurring
      in the hemocytes of the Pacific oyster. 

PMID- 24317473
TI  - Champacyclin, a new cyclic octapeptide from Streptomyces strain C42 isolated from
      the Baltic Sea.
AB  - New isolates of Streptomyces champavatii were isolated from marine sediments of
      the Gotland Deep (Baltic Sea), from the Urania Basin (Eastern Mediterranean), and
      from the Kiel Bight (Baltic Sea). The isolates produced several oligopeptidic
      secondary metabolites, including the new octapeptide champacyclin (1a) present in
      all three strains. Herein, we report on the isolation, structure elucidation and
      determination of the absolute stereochemistry of this isoleucine/leucine (Ile/Leu
      = Xle) rich cyclic octapeptide champacyclin (1a). As 2D nuclear magnetic
      resonance (NMR) spectroscopy could not fully resolve the structure of (1a),
      additional information on sequence and configuration of stereocenters were
      obtained by a combination of multi stage mass spectrometry (MSn) studies, amino
      acid analysis, partial hydrolysis and subsequent enantiomer analytics with gas
      chromatography positive chmical ionization/electron impact mass spectrometry (GC
      PCI/EI-MS) supported by comparison to reference dipeptides. Proof of the head-to
      tail cyclization of (1a) was accomplished by solid phase peptide synthesis (SPPS)
      compared to an alternatively side chain cyclized derivative (2). Champacyclin
      (1a) is likely synthesized by a non-ribosomal peptide synthetase (NRPS), because
      of its high content of (D)-amino acids. The compound (1a) showed antimicrobial
      activity against the phytopathogen Erwinia amylovora causing the fire blight
      disease of certain plants.

PMID- 24317474
TI  - Hypoxia reduces the efficiency of elisidepsin by inhibiting hydroxylation and
      altering the structure of lipid rafts.
AB  - The mechanism of action of elisidepsin (PM02734, Irvalec(r)) is assumed to
      involve membrane permeabilization via attacking lipid rafts and hydroxylated
      lipids. Here we investigate the role of hypoxia in the mechanism of action of
      elisidepsin. Culturing under hypoxic conditions increased the half-maximal
      inhibitory concentration and decreased the drug's binding to almost all cell
      lines which was reversed by incubation of cells with 2-hydroxy palmitic acid. The
      expression of fatty acid 2-hydroxylase was strongly correlated with the
      efficiency of the drug and inversely correlated with the effect of hypoxia.
      Number and brightness analysis and fluorescence anisotropy experiments showed
      that hypoxia decreased the clustering of lipid rafts and altered the structure of
      the plasma membrane. Although the binding of elisidepsin to the membrane is non
      cooperative, its membrane permeabilizing effect is characterized by a Hill
      coefficient of ~3.3. The latter finding is in agreement with elisidepsin-induced
      clusters of lipid raft-anchored GFP visualized by confocal microscopy. We propose
      that the concentration of elisidepsin needs to reach a critical level in the
      membrane above which elisidepsin induces the disruption of the cell membrane.
      Testing for tumor hypoxia or the density of hydroxylated lipids could be an
      interesting strategy to increase the efficiency of elisidepsin. 

PMID- 24317476
TI  - cDNA microarray and bioinformatic analysis for the identification of key genes in
      Alzheimer's disease.
AB  - In this study, gene expression profiles in peripheral blood monocytes from
      patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) were
      compared with those of healthy individuals to identify key differentially
      expressed genes (DEGs), in an effort to broaden our understanding of the
      pathogenesis of these diseases and identify potential therapeutic targets. The
      microarray data set GSE18309 was downloaded from Gene Expression Omnibus,
      including 3 AD, 3 MCI and 3 normal control (NC) samples. Raw data were processed
      and differential analysis was performed using the R multtest package. Two groups
      of comparisons (AD vs. NC and MCI vs. NC) were conducted and two groups of DEGs
      were acquired. The common DEGs were selected, for which functional enrichment
      analysis, as well as pathway enrichment analysis were performed to determine
      their roles in the development of the diseases in question. A total of 405 DEGs
      were identified in the AD vs. NC samples and 395 in the MCI vs. NC samples. A
      total of 60 common DEGs were obtained. Functional enrichment analysis revealed
      that the most common functions of the DEGs identified were response to nutrients,
      muscle contraction and cellular homeostasis. As shown by pathway enrichment
      analysis, the most common pathway associated with the DEGs identifed was the
      neuroactive ligand-receptor interaction pathway. A range of DEGs was identified
      in the present study, which may help to disclose the molecular mechanisms
      responsible for AD and may thus provide potential novel therapeutic strategies
      for Ad.

PMID- 24317475
TI  - Anticancer and cancer preventive properties of marine polysaccharides: some
      results and prospects.
AB  - Many marine-derived polysaccharides and their analogues have been reported as
      showing anticancer and cancer preventive properties. These compounds demonstrate
      interesting activities and special modes of action, differing from each other in
      both structure and toxicity profile. Herein, literature data concerning
      anticancer and cancer preventive marine polysaccharides are reviewed. The
      structural diversity, the biological activities, and the molecular mechanisms of
      their action are discussed. 

PMID- 24317477
TI  - Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant
      chemotherapy.
AB  - S-1 has been recommended as adjuvant chemotherapy in patients after curative
      surgery for gastric cancer. However, some patients suffer recurrence even after S
      1 adjuvant chemotherapy. The present study was conducted to find a predictive
      marker of the efficacy of S-1 adjuvant chemotherapy. We examined the microRNA
      (miRNA) expression of 35 patients who underwent S-1 adjuvant chemotherapy after
      curative surgery (R0) for pathological stage II or III gastric cancer. miRNAs
      were extracted from formalin-fixed, paraffin-embedded specimens for analysis and
      miRNA expression was examined using miRNA oligo chips. Fifteen patients relapsed
      and 20 did not over 5 years. Five miRNAs (miR-92b, 422a, 4732-5p, 4758-3p and
      221) were highly expressed according to the tumor/normal (T/N) ratio in the
      patients who relapsed but not in those who did not relapse (P-value <0.05) by
      microarray analysis. If tumors showed high expression of 4 miRNAs (miR-92b, 422a,
      4732-5p and 4758-3p) their positive predictive value of relapse was 93.8% and
      negative predictive value was 92.3%. In this case, their disease-free survival
      rate and overall survival rate were very poor. Our findings indicate that miR
      92b, miR-422a, miR-4732-5p and miR-4758-3p are closely associated with relapse
      following S-1 adjuvant chemotherapy in gastric cancer. 

PMID- 24317478
TI  - ONO-5334, a cathepsin K inhibitor, improves bone strength by preferentially
      increasing cortical bone mass in ovariectomized rats.
AB  - This study compared the effects of ONO-5334, a cathepsin K inhibitor, with those
      of alendronate on bone mass and strength in ovariectomized rats. Ovariectomy
      resulted in significant elevation in urinary deoxypyridinoline and plasma C
      terminal cross-linking telopeptide of type I collagen (CTX) 8 weeks after
      surgery. Peripheral quantitative computed tomography analysis showed that total,
      trabecular, and cortical bone mineral content (BMC) decreased in the proximal
      tibia, which was paralleled with a significant decline in bone strength.
      Treatment with ONO-5334 (0.12, 0.6, 3 or 15 mg/kg) once daily for 8 weeks dose
      dependently restored the decrease in total BMC and bone mineral density (BMD) in
      the proximal tibia and suppressed urinary deoxypyridinoline and plasma CTX
      levels. Alendronate (1 mg/kg, once daily) also fully restored these bone mass
      parameters. Separate analysis of trabecular and cortical bones, however, showed
      that ONO-5334 only partially restored trabecular BMD and BMC at 15 mg/kg, whereas
      alendronate fully restored these parameters. On the other hand, ONO-5334
      increased both cortical BMD and BMC with an effect more potent than that of
      alendronate. Bone geometric analysis indicated that ONO-5334 at 15 mg/kg
      decreased endosteal circumference without affecting periosteal circumference,
      resulting in marked increase in cortical thickness. Interestingly, the effects of
      ONO-5334 on bone strength parameters were more prominent than those of
      alendronate, although the two test compounds had a similar effect on total BMC.
      Taken together, our results indicate that ONO-5334 has pharmacological
      characteristics different from those of alendronate and may offer a unique
      therapy for patients with osteoporosis.

PMID- 24317479
TI  - A new signal sequence for recombinant protein secretion in Pichia pastoris.
AB  - Pichia pastoris is one of the most widely used expression systems for the
      secretory expression of recombinant proteins. The secretory expression in P.
      pastoris usually makes use of the prepro MATalpha sequence from Saccharomyces
      cerevisiae, which has a dibasic amino acid cleavage site at the end of the signal
      sequence. This is efficiently processed by Kex2 protease, resulting in the
      secretion of high levels of proteins to the medium. However, the proteins that
      are having the internal accessible dibasic amino acids such as KR and RR in the
      coding region cannot be expressed using this signal sequence, as the protein will
      be fragmented. We have identified a new signal sequence of 18 amino acids from a
      P. pastoris protein that can secrete proteins to the medium efficiently. The PMT1
      gene-inactivated P. pastoris strain secretes a ~30 kDa protein into the
      extracellular medium. We have identified this protein by determining its N
      terminal amino acid sequence. The protein secreted has four DDDK concatameric
      internal repeats. This protein was not secreted in the wild-type P. pastoris
      under normal culture conditions. We show that the 18-amino-acid signal peptide at
      the N-terminal of this protein is useful for secretion of heterologous proteins
      in Pichia.

PMID- 24317480
TI  - Interaction between the quorum sensing and stringent response regulation systems
      in the enterohemorrhagic Escherichia coli O157:H7 EDL933 strain.
AB  - Quorum sensing and the stringent response are well-known regulation systems for
      the expression of virulence genes in enterohemorrhagic Escherichia coli (EHEC).
      However, how these two systems interact is not well known. E. coli strains with
      mutations in two regulation systems, DeltaluxS (ECM101) and
      DeltaluxSDeltarelADeltaspoT (ECM201), and the DeltaluxS complement strain to
      ECM201 (ECM202) were created from EHEC O157:H7 EDL933 to investigate how the
      regulatory systems interact. The phenotypic changes of the mutant strains were
      characterized and compared with the wild type. The mutant strains exhibited no
      obvious growth defects, although acid resistance and cellular cytotoxicity were
      decreased significantly in all the mutant strains. Phenotypic characterization
      revealed that mutations in the stringent response system (ECM201 and ECM202)
      influenced the metabolic (defective utilization of arabinose and L-sorbose) and
      enzymatic activities (decreased trypsin activity, and increased alpha-glucosidase
      activity). In contrast, the quorum sensing system mutant (ECM101) did not display
      these phenotypes. The motility of the quorum sensing system mutant (ECM101) was
      unchanged, but mutation in the stringent response system influenced the motility.
      Our results suggest that quorum sensing interacts with the stringent response
      regulation system.

PMID- 24317481
TI  - Peroxidase and photoprotective activities of magnesium protoporphyrin IX.
AB  - Magnesium-protoporphyrin IX (Mg-PPn), which is formed through chelation of
      protoporphyrin IX (PPn) with Mg ion by Mg chelatase, is the first intermediate
      for the (bacterio)chlorophyll biosynthetic pathway. Interestingly, Mg-PPn
      provides peroxidase activity (approximately 4 * 10(-2) units/micrometer)
      detoxifying H2O2 in the presence of electron donor(s). The peroxidase activity
      was not detected unless PPn was chelated with Mg ion. Mg-PPn was found freely
      diffusible through the membrane of Escherichia coli and Vibrio vulnificus,
      protecting the cells from H2O2. Furthermore, unlike photosensitizers such as
      tetracycline and PPn, Mg-PPn did not show any phototoxicity, but rather it
      protected cell from ultraviolet (UV)-A-induced stress. Thus, the exogenous Mg-PPn
      could be used as an antioxidant and a UV block to protect cells from H2O2 stress
      and UV-induced damage. 

PMID- 24317482
TI  - Diversity and saline resistance of endophytic fungi associated with Pinus
      thunbergii in coastal shelterbelts of Korea.
AB  - The Black Pine, Pinus thunbergii, is widely distributed along the eastern coast
      of Korea and its importance as a shelterbelt was highlighted after tsunamis in
      Indonesia and Japan. The root endophytic diversity of P. thunbergii was
      investigated in three coastal regions; Goseong, Uljin, and Busan. Fungi were
      isolated from the root tips, and growth rates of pure cultures were measured and
      compared between PDA with and without 3% NaCl to determine their saline
      resistance. A total of 259 isolates were divided into 136 morphotypes, of which
      internal transcribed spacer region sequences identified 58 species.
      Representatives of each major fungi phylum were present: 44 Ascomycota, 8
      Zygomycota, and 6 Basidiomycota. Eighteen species exhibited saline resistance,
      many of which were Penicillium and Trichoderma species. Shoreline habitats
      harbored higher saline-tolerant endophytic diversity compared with inland sites.
      This investigation indicates that endophytes of P. thunbergii living closer to
      the coast may have higher resistance to salinity and potentially have specific
      relationships with P. thunbergii.

PMID- 24317483
TI  - Heterologous expression and biochemical characterization of glucose isomerase
      from Thermobifida fusca.
AB  - Glucose isomerase (GIase) catalyzes the isomerization of D-glucose to D-fructose.
      The GIase from Thermobifida fusca WSH03-11 was expressed in Escherichia coli
      BL21(DE3), and the purified enzyme took the form of a tetramer in solution and
      displayed a pI value of 5.05. The temperature optimum of GIase was 80  degrees C
      and its half life was about 2 h at 80  degrees C or 15 h at 70  degrees C. The pH
      optimum of GIase was 10 and the enzyme retained 95 % activity over the pH range
      of 5-10 after incubating at 4  degrees C for 24 h. Kinetic studies showed that
      the K m and K cat values of the enzyme are 197 mM and 1,688 min(-1),
      respectively. The maximum conversion yield of glucose (45 %, w/v) to fructose of
      the enzyme was 53 % at pH 7.5 and 70  degrees C. The present study provides the
      basis for the industrial application of recombinant T. fusca GIase in the
      production of high fructose syrup.

PMID- 24317484
TI  - Automatic identification of structured process models based on biological
      phenomena detected in (fed-)batch experiments.
AB  - In this paper, we present a set of methods to automatically propose structured
      process models from an automated analysis of (fed-)batch experiments. Therefore,
      the measurements are numerically compensated for the influence of feeding and
      sampling, and the qualitative behavior of the measurements is revealed. As
      measurements from fermentations are inherently noisy, we introduce a method that
      divides the compensated curves into several episodes in a probabilistic framework
      to better handle these shortcomings. The probability of biological phenomena that
      reveal crucial information about the underlying reaction network is calculated.
      Since the phenomena detection is measurement-driven, its reliability depends on
      the measurement situation, e.g., the number of samples taken and experiments
      considered, measurement noise, etc. We show a possible approach to test the
      uncertainty of the phenomena detection against these influences. Finally, model
      structures are proposed automatically based on the detected biological phenomena.
      An experimental validation of the approach is shown, using real fermentation data
      from fed-batch cultivations of Streptomyces tendae. 

PMID- 24317485
TI  - Cycle length and COD/N ratio determine properties of aerobic granules treating
      high-nitrogen wastewater.
AB  - Aerobic granule characteristic in sequencing batch reactors treating high
      nitrogen digester supernatant was investigated at cycle lengths (t) of 6, 8 and
      12 h with the COD/N ratios in the influent of 4.5 and 2.3. The biomass production
      (Y obs) correlated with the extracellular polymeric substances (EPS) in grams per
      COD removed. Denitrification efficiency significantly decreased as the amount of
      EPS in biomass increased, suggesting that organic assimilation in EPS hampers
      nitrogen removal. Granule hydrophobicity was highest at t of 8 h; the t has to be
      long enough to remove pollutants, but not so long that excessive biomass
      starvation causes extracellular protein consumption that decreases
      hydrophobicity. At a given t, reducing the COD/N ratio improved hydrophobicity
      that stimulates cell aggregation. At t of 6 h and the COD/N ratio of 2.3, the
      dominance of 0.5-1.0 mm granules favored simultaneous nitrification and
      denitrification and resulted in the highest nitrogen removal.

PMID- 24317486
TI  - Attentional dwell times for targets and masks.
AB  - Studies on the temporal dynamics of attention have shown that the report of a
      masked target (T2) is severely impaired when the target is presented with a delay
      (stimulus onset asynchrony) of less than 500 ms after a spatially separate masked
      target (T1). This is known as the attentional dwell time. Recently, we have
      proposed a computational model of this effect building on the idea that a
      stimulus retained in visual short-term memory (VSTM) takes up visual processing
      resources that otherwise could have been used to encode subsequent stimuli into
      VSTM. The resources are locked until the stimulus in VSTM has been recoded, which
      explains the long dwell time. Challenges for this model and others are findings
      by Moore, Egeth, Berglan, and Luck (1996) suggesting that the dwell time is
      substantially reduced when the mask of T1 is removed. Here we suggest that the
      mask of T1 modulates performance not by noticeably affecting the dwell time but
      instead by acting as a distractor drawing processing resources away from T2. This
      is consistent with our proposed model in which targets and masks compete for
      attentional resources and attention dwells on both. We tested the model by
      replicating the study by Moore et al., including a new condition in which T1 is
      omitted but the mask of T1 is retained. Results from this and the original study
      by Moore et al. are modeled with great precision. 

PMID- 24317488
TI  - Structure of a pathogenic type 3 secretion system in action.
AB  - Type 3 secretion systems use 3.5-megadalton syringe-like, membrane-embedded
      'injectisomes', each containing an ~800-A-long needle complex to connect
      intracellular compartments of infectious bacteria and hosts. Here we identify
      requirements for substrate association with, transport through and exit from the
      injectisome of Salmonella enterica serovar Typhimurium. This guided the design of
      substrates that become trapped within the secretion path and enabled
      visualization of injectisomes in action in situ. We used cryo-EM to define the
      secretion path, providing a structural explanation as to why effector proteins
      must be unfolded during transport. Furthermore, trapping of a heterologous
      substrate in the needle prevents secretion of natural bacterial effectors.
      Together, the data reveal the path of protein secretion across multiple membranes
      and show that mechanisms rejecting unacceptable substrates can be undermined, and
      transport of bacterial effectors across an already assembled type 3 secretion
      system can be inhibited. 

PMID- 24317489
TI  - Transcription-generated torsional stress destabilizes nucleosomes.
AB  - As RNA polymerase II (Pol II) transcribes a gene, it encounters an array of well
      ordered nucleosomes. How it traverses through this array in vivo remains
      unresolved. One model proposes that torsional stress generated during
      transcription destabilizes nucleosomes ahead of Pol II. Here, we describe a
      method for high-resolution mapping of underwound DNA, using next-generation
      sequencing, and show that torsion is correlated with gene expression in
      Drosophila melanogaster cells. Accumulation of torsional stress, through
      topoisomerase inhibition, results in increased Pol II at transcription start
      sites. Whereas topoisomerase I inhibition results in increased nascent RNA
      transcripts, topoisomerase II inhibition causes little change. Despite the
      different effects on Pol II elongation, topoisomerase inhibition results in
      increased nucleosome turnover and salt solubility within gene bodies, thus
      suggesting that the elongation-independent effects of torsional stress on
      nucleosome dynamics contributes to the destabilization of nucleosomes. 

PMID- 24317490
TI  - A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that
      of allosteric activators.
AB  - Glucokinase (GK) is a glucose-phosphorylating enzyme that regulates insulin
      release and hepatic metabolism, and its loss of function is implicated in
      diabetes pathogenesis. GK activators (GKAs) are attractive therapeutics in
      diabetes; however, clinical data indicate that their benefits can be offset by
      hypoglycemia, owing to marked allosteric enhancement of the enzyme's glucose
      affinity. We show that a phosphomimetic of the BCL-2 homology 3 (BH3) alpha-helix
      derived from human BAD, a GK-binding partner, increases the enzyme catalytic rate
      without dramatically changing glucose affinity, thus providing a new mechanism
      for pharmacologic activation of GK. Remarkably, BAD BH3 phosphomimetic mediates
      these effects by engaging a new region near the enzyme's active site. This
      interaction increases insulin secretion in human islets and restores the function
      of naturally occurring human GK mutants at the active site. Thus, BAD
      phosphomimetics may serve as a new class of GKAs. 

PMID- 24317491
TI  - Copper-transporting P-type ATPases use a unique ion-release pathway.
AB  - Heavy metals in cells are typically regulated by PIB-type ATPases. The first
      structure of the class, a Cu(+)-ATPase from Legionella pneumophila (LpCopA),
      outlined a copper transport pathway across the membrane, which was inferred to be
      occluded. Here we show by molecular dynamics simulations that extracellular water
      solvated the transmembrane (TM) domain, results indicative of a Cu(+)-release
      pathway. Furthermore, a new LpCopA crystal structure determined at 2.8-A
      resolution, trapped in the preceding E2P state, delineated the same passage, and
      site-directed-mutagenesis activity assays support a functional role for the
      conduit. The structural similarities between the TM domains of the two
      conformations suggest that Cu(+)-ATPases couple dephosphorylation and ion
      extrusion differently than do the well-characterized PII-type ATPases. The ion
      pathway explains why certain Menkes' and Wilson's disease mutations impair
      protein function and points to a site for inhibitors targeting pathogens. 

PMID- 24317492
TI  - Overlapping chromatin-remodeling systems collaborate genome wide at dynamic
      chromatin transitions.
AB  - ATP-dependent chromatin remodeling is an essential process required for the
      dynamic organization of chromatin structure. Here we describe the genome-wide
      location and activity of three remodeler proteins with diverse physiological
      functions in the mouse genome: Brg1, Chd4 and Snf2h. The localization patterns of
      all three proteins substantially overlap with one another and with regions of
      accessible chromatin. Furthermore, using inducible mutant variants, we
      demonstrate that the catalytic activity of these proteins contributes to the
      remodeling of chromatin genome wide and that each of these remodelers can
      independently regulate chromatin reorganization at distinct sites. Many regions
      require the activity of more than one remodeler to regulate accessibility. These
      findings provide a dynamic view of chromatin organization and highlight the
      differential contributions of remodelers to chromatin maintenance in higher
      eukaryotes. 

PMID- 24317493
TI  - Nanoscale viscoelasticity of extracellular matrix proteins in soft tissues: A
      multiscale approach.
AB  - It is hypothesized that the bulk viscoelasticity of soft tissues is determined by
      two length-scale-dependent mechanisms: the time-dependent response of the
      extracellular matrix (ECM) proteins at the nanometer scale and the biophysical
      interactions between the ECM solid structure and interstitial fluid at the
      micrometer scale. The latter is governed by poroelasticity theory assuming free
      motion of the interstitial fluid within the porous ECM structure. In a recent
      study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013.
      J. Mech. Behav. Biomed. Mater.), atomic force microscopy was used to measure the
      response of porcine vocal folds to a creep loading and a 50-nm sinusoidal
      oscillation. A constitutive model was calibrated and verified using a finite
      element model to accurately predict the nanoscale viscoelastic moduli of ECM. A
      generally good correlation was obtained between the predicted variation of the
      viscoelastic moduli with depth and that of hyaluronic acids in vocal fold tissue.
      We conclude that hyaluronic acids may regulate vocal fold viscoelasticity. The
      proposed methodology offers a characterization tool for biomaterials used in
      vocal fold augmentations. 

PMID- 24317494
TI  - Deformation-induced changeable Young's modulus with high strength in beta-type Ti
      Cr-O alloys for spinal fixture.
AB  - In order to meet the requirements of the patients and surgeons simultaneously for
      spinal fixation applications, a novel biomedical alloy with a changeable Young's
      modulus, that is, with a low Young's modulus to prevent the stress-shielding
      effect for patients and a high Young's modulus to suppress springback for
      surgeons, was developed. In this study, the chromium and oxygen contents in
      ternary Ti(11, 12 mass%)Cr-(0.2, 0.4, 0.6 mass%)O alloys were optimized in order
      to achieve a changeable Young's modulus via deformation-induced omega-phase
      transformation with good mechanical properties. The Young's moduli of all the
      examined alloys increase after cold rolling, which is attributed to the
      deformation-induced omega-phase transformation. This transformation is suppressed
      by oxygen but enhanced with lower chromium content, which is related to the
      beta(bcc)-lattice stability. Among the examined alloys, the Ti-11Cr-0.2O alloy
      shows a low Young's modulus of less than 80GPa in the solution-treated (ST)
      condition and a high Young's modulus of more than 90GPa in the cold rolled (CR)
      condition. The Ti-11Cr-0.2O alloy also exhibits a high tensile strength, above
      1000MPa, with an acceptable elongation of ~12% in the ST condition. Furthermore,
      the Ti-11Cr-0.2O alloy exhibits minimal springback. This value of springback is
      the closest to that of Ti64 ELI alloy among the compared alloys. Therefore, the
      Ti-11Cr-0.2O alloy, which has a good balance between large changeable Young's
      modulus, high tensile strength, good plasticity, and minimal springback, is
      considered to be a potential candidate for spinal fixation applications.

PMID- 24317495
TI  - Trauma-hemorrhagic shock induces a CD36-dependent RBC endothelial-adhesive
      phenotype.
AB  - OBJECTIVE: Microvascular dysfunction is a key element in the development of the
      multiple organ dysfunction syndrome. Although the mechanisms for this response
      are unclear, RBC adhesion to endothelium may initiate intravascular occlusion
      leading to ischemic tissue injury. Thus, we tested the hypothesis that trauma
      hemorrhage induces RBC-endothelial cell adhesion. DESIGN: Prospective in vivo and
      in vitro animal study and analysis of patient blood samples. SETTING: University
      research laboratory and hospital emergency and trauma units. INTERVENTION: We
      initially assayed RBC adhesion to endothelial cells in vitro using RBCs obtained
      from rats subjected to trauma-hemorrhagic shock or sham shock as well as from
      severely injured trauma patients. Subsequently, we measured the role of putative
      RBCs and endothelial cell receptors in the increased RBC-endothelial cell
      adhesive response. MAIN RESULTS: In both rats and humans, trauma-hemorrhagic
      shock increased RBC adhesion to endothelium as well as increasing several
      putative RBC surface adhesion molecules including CD36. The critical factor
      leading to RBC-endothelial cell adhesion was increased surface RBC CD36
      expression. Adhesion of trauma-hemorrhagic shock RBCs was mediated, at least in
      part, by the binding of RBC CD36 to its cognate endothelial receptors
      (alphaVbeta3 and VCAM-1). Gut-derived factors carried in the intestinal
      lymphatics triggered these trauma-hemorrhagic shock-induced RBC changes because
      1) preventing trauma-hemorrhagic shock intestinal lymph from reaching the
      systemic circulation abrogated the RBC effects, 2) in vitro incubation of naive
      whole blood with trauma-hemorrhagic shock lymph replicated the in vivo trauma
      hemorrhagic shock-induced RBC changes while 3) injection of trauma-hemorrhagic
      shock lymph into naive animals recreated the RBC changes observed after actual
      trauma-hemorrhagic shock. CONCLUSIONS: 1) Trauma-hemorrhagic shock induces rapid
      RBC adhesion to endothelial cells in patients and animals. 2) Increased RBC CD36
      expression characterizes the RBC-adhesive phenotype. 3) The RBC phenotypic and
      functional changes were induced by gut-derived humoral factors. These novel
      findings may explain the microvascular dysfunction occurring after trauma
      hemorrhagic shock, sepsis, and other stress states.

PMID- 24317496
TI  - Agitated saline bubble-enhanced transthoracic echocardiography: a novel method to
      visualize the position of central venous catheter.
AB  - OBJECTIVES: The purpose of this study is to describe a novel method to visualize
      the position of central venous catheters, which is safe, expeditious, and less
      expensive than the routine postprocedural chest radiograph. DESIGN: Retrospective
      comparative study. SETTING: Dialysis Center of the Department of Nephrology,
      Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany.
      PATIENTS: Two hundred and two adult patients undergoing central venous catheter
      placement for dialysis, plasmapheresis, or administration of medication and
      solutions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data of 202 adult
      patients with 219 central venous catheterizations were retrospectively analyzed.
      Each catheter insertion was followed by an agitated saline bubble-enhanced
      transthoracic echocardiography, which was used to localize the tip of the
      catheter. The position of catheter was then controlled by chest radiograph in all
      cases. During the 13-month study period, two catheter malpositions occurred. Both
      were identified by agitated saline bubble-enhanced transthoracic echocardiography
      and confirmed by chest radiograph. The mean time between catheter insertion and
      chest radiograph control (28.3 min) was clearly longer than agitated saline
      bubble-enhanced transthoracic echocardiography (3.2 min) (p < 0.001). The total
      costs of the procedure were reduced by 86.7-95.0%. Specific complications related
      to the procedure were not observed. CONCLUSIONS: The results revealed that the
      accuracy of agitated saline bubble-enhanced transthoracic echocardiography is
      equivalent to the chest radiograph. It offers a safe, cost-effective, expeditious
      alternative to routine chest radiograph for position controls of central venous
      catheters.

PMID- 24317497
TI  - Evaluating the efficacy of a web-based program (diapason) for informal caregivers
      of patients with Alzheimer's disease: protocol for a randomized clinical trial.
AB  - BACKGROUND: Informal caregivers (CGs) of patients with Alzheimer's disease are at
      risk of suffering from psychological and physical weakening. Several
      psychoeducational interventions have been designed to prevent stress and burden
      of caregivers. In France, despite health authorities' recommendations, to our
      knowledge there is no rigorously assessed Web-based psychoeducational program to
      date. OBJECTIVE: The objective of our study was to assess the efficacy of a
      French Web-based psychoeducational program (called Diapason) with an unblinded
      randomized clinical trial. METHODS: In this protocol, 80 informal caregivers of
      patients followed at Broca Hospital are recruited offline and randomized in the
      experimental condition (EC) or the control condition (CC). The volunteers in EC
      have to visit a closed online user group at least once a week and validate one
      new session of this fully automated Web program, during 12 weeks. Each week a new
      thematic is added to the website. The participants in the CC receive usual care,
      and have access to the Diapason program after their participation (6 months).
      Face-to-face evaluations for both groups are planned every 3 months (M0-M3 and
      M6). The main objective of this program is to provide CGs with information on the
      disease process, how to prevent psychological strain (using anticipation and
      relaxation techniques), and offering a virtual space (forum) to discuss with
      other caregivers. The primary outcome of this study is the self-perceived stress,
      while self-efficacy, burden, depression, and self-perceived health status are
      defined as secondary outcomes. Other variables that might have an impact on the
      program efficacy are collected. RESULTS: This protocol was accepted for funding.
      The enrollment began in October 2011, and participants currently recruited will
      finish their evaluations in January 2014. The results are expected for June 2014.
      CONCLUSIONS: Findings might provide empirical evidence on: (1) the feasibility of
      an Internet-based program in the French context, (2) the effectiveness of a Web
      based program for informal caregivers, and (3) the identification of caregivers
      who will benefit from this type of intervention. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01430286; http://clinicaltrials.gov/ct2/show/NCT01430286
      (Archived by WebCite at http://www.webcitation/6KxHaRspL).

PMID- 24317499
TI  - Determination of precise pyrimidine cationic structure by vacuum ultraviolet mass
      analyzed threshold ionization spectroscopy.
AB  - The vibrational spectrum of a pyrimidine cation in the ground electronic state
      was obtained using vacuum ultraviolet mass-analyzed threshold ionization (VUV
      MATI) spectroscopy. Accurate ionization energy of pyrimidine was determined from
      the 0-0 band position in the VUV-MATI spectrum and was measured by varying the
      PFI field to the zero field limit, which is 75,258 +/- 7 cm(-1) (9.3308 eV). The
      spectrum displayed a large number of vibrational peaks, which could be nearly
      completely assigned through Franck-Condon analysis performed with variations of
      geometrical parameters at the B3LYP/cc-pVTZ level. Based on the excellent
      agreement between experimental and calculated results, the definite geometry of
      the pyrimidine cation in the ground electronic state was determined to be a
      planar structure with C2v symmetry with a decreased N-N distance in the ring.

PMID- 24317498
TI  - Sodium fluoride induces apoptosis through the downregulation of hypoxia-inducible
      factor-1alpha in primary cultured rat chondrocytes.
AB  - It has been reported that sodium fluoride (NaF) suppresses the proliferation and
      induces apoptosis of chondrocytes. However, the cellular and molecular mechanisms
      of the effect have not been elucidated. Therefore, the aim of this study was to
      evaluate the mechanisms of the effects of NaF on primary cultured rat
      chondrocytes in vitro. Chondrocytes were treated with NaF at concentrations of 0,
      1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 mM. Cell viability decreased and the rate of
      apoptotic cells increased significantly with the gradient concentration of NaF in
      a time- and dose-dependent manner. Electron microscopy revealed cytoplasmic,
      organelle and nuclear alterations in the ultrastructure of chondrocytes exposed
      to various NaF concentrations. The cell cycle distribution was analyzed by flow
      cytometry, and the results indicated that NaF induced G2 cell cycle arrest.
      Western blotting was used to detect the apoptotic pathways. Downregulation of the
      Bcl-2 protein and upregulation of Bax, cleaved caspase-9, -12 and -3 proteins
      suggested that NaF was capable of inducing apoptosis through the mitochondrial
      and endoplasmic reticulum pathways. The results also showed that the levels of
      hypoxia-inducible factor 1alpha (HIF-1alpha), sex determining region Y box gene 9
      (Sox9) and the collagen II (Col II) protein of the NaF groups were lower compared
      to those of the control groups. Thus, NaF may induce apoptosis through the
      downregulation of HIF-1alpha and disrupt the synthesis of extracellular matrix
      (ECM) through the downregulation of HIF-1alpha via the Sox9 pathway in primary
      cultured rat chondrocytes.

PMID- 24317500
TI  - Isozymes, plant population genetic structure and genetic conservation.
AB  - The exploration, conservation and use of the genetic resources of plants is a
      contemporary issue which requires a multidisciplinary approach. Here the role of
      population genetic data, particularly those derived from electrophoretic analysis
      of protein variation, is reviewed. Measures of the geographic structure of
      genetic variation are used to check on sampling theory. Current estimates justify
      the contention that alleles which have a highly localised distribution, yet are
      in high frequency in some neighbourhoods, represent a substantial fraction of the
      variation. This class, which is the most important class in the framing of
      sampling strategies, accounts for about 20-30% of variants found in 12 plant
      species. The importance of documenting possible coadapted complexes and gene
      environment relationships is discussed. Furthermore, the genetic structure of
      natural populations of crop relatives might suggest the best structure to use in
      the breeding of crops for reduced vulnerability to pest and disease attack, or
      for adaptation to inferior environments. The studies reported to date show that
      whilst monomorphic natural populations do occur, particularly in inbreeding
      colonisers, or at the extreme margins of the distribution, polymorphism seems to
      be the more common mode. It is stressed here that the genetic resources of the
      wild relatives of crop plants should be systematically evaluated. These sources
      will supplement, and might even rival, the primitive land races in their
      effectiveness in breeding programmes. We may look forward to a wider application
      of gel electrophoresis in the evaluation of plant genetic resources because this
      technique is currently the best available for detecting genetic differences close
      to the DNA level on samples of reasonable size. 

PMID- 24317501
TI  - Quantitative genetic studies at the tetraploid and hexaploid levels in alfalfa.
AB  - Two sets of diallel crosses involving seven tetraploid and five hexaploid alfalfa
      lines, previously selected for seed and forage yield, are studied. On the basis
      of combining ability and heritability estimates the following conclusion is
      drawn. The dominant and epistatic interactions (heterozygosity) are the major
      components in the expression of variability for yield and characters associated
      with yield in tetraploid populations. In hexaploid populations, however, there is
      an appreciable amount of additive variance, and the additive effect of genes
      along with interaction of various forms may account for the expressed variability
      for all the characters studied. Better genes and desirable interactions (possibly
      through heterozygosity) are the two essential genetic components of yield. The
      selection of better genes is feasible, but by itself will not produce the desired
      results. Future improvement may therefore depend on the utilization of heterosis
      and other forms of interactions. There is, in general, a very strong genetic
      correlation between yield and its components, and therefore, when a direct
      selection for yield is not feasible, the selection program may rely on a number
      of closely related characters. 

PMID- 24317502
TI  - Genetic analysis of field germination in soybean (Glycine max. (L) merill.).
AB  - Genetic analysis for germination percentage was carried out in the F3 and F4
      generations of a diallel cross involving six promising genotypes of soybean.
      Results indicated a high amount of genetic variability and a moderately high
      heritability together with genetic advance, suggesting a possible improvement for
      this character through hybridization and selection. Correlations at different
      levels revealed a strong negative association of germination with only one seed
      character: seed weight. This observation was further confirmed from path
      coefficient analysis. These findings strongly suggest that to base selection on
      seed weight which may not influence the seed quality of soybean. 

PMID- 24317503
TI  - Assessment of barley varieties as potential pollen-parents for F1 - hybrid
      varieties.
AB  - The choice of male parents for an F1-hybrid barley variety depends upon a number
      of characteristics, among which will be the combining ability for yield, the
      transference of disease resistance and the ability to release large quantities of
      viable pollen to ensure a high set of F1 -hybrid seed on the male-sterile Une.A
      number of cultivars were assessed as potential pollen parents using a common male
      sterile variety. Various experimental methods to assess the potential of male
      parents were used at locations in the United Kingdom and elsewhere in Western
      Europe over a period of three years. Significant differences were demonstrated
      between the cross-pollinating ability of varieties; 'good' pollinators gave
      consistent results. A marked effect of crossing-block size was found and there
      was also some evidence of environmental interactions. 

PMID- 24317504
TI  - Biosystematics and agronomic potential of some weedy and cultivated amaranths.
AB  - Three weedy amaranths (Amarantkus hybridus, A. retroflexus and A. powellii) from
      nine California sites, three domesticated species (A. caudatus, A.
      hypochondriacus and A. cruentus) from the USDA plant inventory as well as other
      sources and a naturally-occurring crop-weed hybrid were studied for numerical
      taxonomy using morphological and allozyme variation data. The crop and weedy
      species groups were easily separated and the hybrid populations were found to be
      intermediate. Surprisingly, very little intraspecific variation was present.
      Crop, weed and hybrid amaranths were also compared for their yielding ability,
      harvest index, seed efficiency of grain production and protein, popping quality
      and other agronomic traits. Although field plot yields were similar among the
      three groups of species (700 Kg/ha seed without fertilizer treatment and water,
      ranging to 3000 Kg/ha with fertilizer applications of 170 Kg N/ha, and abundant
      water), the harvest index of the weedy group was much higher (25-40%) than the
      domesticated species (10-15%). The allocation of biomass to seed production is
      positively correlated with seed yield in the domesticated but not in the weedy
      types, whereas the percentages of biomass as stem material and as seeds are
      negatively correlated. Several weedy and crop characteristics together should
      provide the basis of new improved cultivars through genetic recombination and
      selection. 

PMID- 24317505
TI  - Inheritance of three electrophoretically determined protein bands in potato
      (Solanum tuberosum L.).
AB  - A modified polyacrylamide gel electrophoresis technique is employed to resolve
      proteins for use as biochemical gene markers in potato. Dominant, duplicate
      dominant and complementary gene action are three modes of inheritance that
      adequately explain the segregation of three respective protein bands in two
      generations of crossing within diploid Phureja X haploid Tuberosum families. 

PMID- 24317506
TI  - Epigenetic programming of reward function in offspring: a role for maternal diet.
AB  - Early life development, through gestation and lactation, represents a timeframe
      of extreme vulnerability for the developing fetus in general, and for the central
      nervous system in particular. An adverse perinatal environment can have a lasting
      negative impact on brain development, increasing the risk for developmental
      disorders and broader psychopathologies. A major determinant of the fetal
      developmental environment is maternal diet. The present review summarizes the
      current literature regarding the effect of poor maternal perinatal nutrition on
      offspring brain development, with an emphasis on reward-related neural systems
      and behaviors. Epigenetic mechanisms represent a likely link between maternal
      diet and persistent changes in offspring brain development, and these mechanisms
      are presented and discussed within the context of perinatal maternal nutrition. 

PMID- 24317508
TI  - p21Waf1/Cip1 deficiency causes multiple mitotic defects in tumor cells.
AB  - As a multifaceted molecule, p21 plays multiple critical roles in cell cycle
      regulation, differentiation, apoptosis, DNA repair, senescence, aging and stem
      cell reprogramming. The important roles of p21 in the interphase of the cell
      cycle have been intensively investigated. The function of p21 in mitosis has been
      proposed but not systematically studied. We show here that p21 is abundant in
      mitosis and binds to and inhibits the activity of Cdk1/cyclin B1. Deficiency of
      p21 prolongs the duration of mitosis by extending metaphase, anaphase and
      cytokinesis. The activity of Aurora B is reduced and the localization of Aurora B
      on the central spindle is disturbed in anaphase cells without p21. Moreover,
      HCT116 p21-/-, HeLa and Saos-2 cells depleted of p21 encounter problems in
      chromosome segregation and cytokinesis. Gently inhibiting the mitotic Cdk1 or add
      back of p21 rescues segregation defect in HCT116 p21-/- cells. Our data
      demonstrate that p21 is important for a fine-tuned control of the Cdk1 activity
      in mitosis, and its proper function facilitates a smooth mitotic progression.
      Given that p21 is downregulated in the majority of tumors, either by the loss of
      tumor suppressors like p53 or by hyperactive oncogenes such as c-myc, this
      finding also sheds new light on the molecular mechanisms by which p21 functions
      as a tumor suppressor. 

PMID- 24317507
TI  - Effects of three kinds of erythropoiesis-stimulating agents on renal anemia in
      Japanese non-dialysis chronic kidney disease patients.
AB  - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are standard therapy for
      chronic kidney disease (CKD) patients with renal anemia. However, few studies
      have compared the effects of different ESAs on anemia in identical pre-dialysis
      CKD patients. METHODS: Seventy-nine patients who switched from epoetin beta to
      darbepoetin alfa (Group 1), and 82 patients who switched from darbepoetin alfa to
      epoetin beta pegol (Group 2) were enrolled in this study. Clinical and laboratory
      parameters were assessed for 6 months before and after switching ESAs. The
      prevalence of adverse events, the dose conversion ratio of ESAs, and the
      frequency of ESA administration were also analyzed. RESULTS: Analysis of variance
      showed that switching ESAs did not significantly change hemoglobin levels for the
      study duration in both groups (mean hemoglobin 10.3-10.5 g/dL in Group 1 and 10.4
      10.7 g/dL in Group 2). Estimated glomerular filtration rate, blood pressure,
      transferrin saturation, ferritin, and albumin remained constant in both groups.
      The prevalence of adverse effects was quite low (0-3.8 %) during both 6-month
      study periods. The mean dose conversion ratio for epoetin beta:darbepoetin alfa
      was 163.7 units:1 MUg and for darbepoetin alfa:epoetin beta pegol was 1.08 MUg:1
      MUg. The intervals of ESA administration significantly differed (epoetin beta
      pegol > darbepoetin alfa > epoetin beta). CONCLUSIONS: Epoetin beta, darbepoetin
      alfa, and epoetin beta pegol are effective and well-tolerated agents for managing
      anemia in Japanese pre-dialysis CKD patients. The intervals of ESA administration
      to maintain a patient's target hemoglobin were longer in the order of epoetin
      beta pegol > darbepoetin alfa > epoetin beta.

PMID- 24317509
TI  - A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating
      cells isolated from a Brca1-associated mouse model of breast cancer.
AB  - Cancer metastasis is a lethal problem that claims the lives of over 90% of cancer
      patients. In this study, we have investigated metastatic potential of cancer stem
      cells (CSCs) isolated from mammary tumors of a Brca1-mutant mouse model. Our data
      indicated that CSCs, which are enriched in CD24(+)CD29(+)/CD49f(+) cell
      population, displayed much higher migration ability than CD24(-)CD29(-)/CD49f(-)
      cells in tissue culture and enhanced metastatic potential in allograft-nude mice.
      CD24(+)CD29(+) cells maintained the ability to differentiate and reconstitute
      heterogeneity in the metastatic tumors whereas CD24(-)CD29(-) cells could not.
      Corresponding to their enhanced metastatic ability, CD24(+)CD29(+) cells
      exhibited features of the epithelial to mesenchymal transition. Finally, using
      short hairpin RNA to knock down CD29 and/or CD49f in metastatic cancer cells, we
      demonstrated that while acute knockdown of CD29 or CD49f alone slightly decreased
      cell migration ability, knockdown of both genes generated a profound effect to
      block their migration, revealing an overlapping, yet critical function of both
      genes in the migration of CSCs. Our findings indicate that in addition to serving
      as markers of CSCs, CD29 and CD49f may also serve as potential therapeutic
      targets for cancer metastasis.

PMID- 24317511
TI  - ROCK has a crucial role in regulating prostate tumor growth through interaction
      with c-Myc.
AB  - Rho-associated kinase (ROCK) has an essential role in governing cell morphology
      and motility, and increased ROCK activity contributes to cancer cell invasion and
      metastasis. Burgeoning data suggest that ROCK is also involved in the growth
      regulation of tumor cells. However, thus far, the molecular mechanisms
      responsible for ROCK-governed tumor cell growth have not been clearly elucidated.
      Here we showed that inhibition of ROCK kinase activity, either by a selective
      ROCK inhibitor Y27632 or by specific ROCK small interfering RNA (siRNA)
      molecules, attenuated not only motility but also the proliferation of PC3
      prostate cancer cells in vitro and in vivo. Importantly, mechanistic
      investigation revealed that ROCK endowed cancer cells with tumorigenic
      capability, mainly by targeting c-Myc. ROCK could increase the transcriptional
      activity of c-Myc by promoting c-Myc protein stability, and ROCK inhibition
      reduced c-Myc-mediated expression of mRNA targets (such as HSPC111) and microRNA
      targets (such as miR-17-92 cluster). We provided evidence demonstrating that
      ROCK1 directly interacted with and phosphorylated c-Myc, resulting in
      stabilization of the protein and activation of its transcriptional activity.
      Suppression of ROCK-c-Myc downstream molecules, such as c-Myc-regulated miR-17,
      also impaired tumor cell growth in vitro and in vivo. In addition, c-Myc was
      shown to exert a positive feedback regulation on ROCK by increasing RhoA mRNA
      expression. Therefore, inhibition of ROCK and its stimulated signaling might
      prove to be a promising strategy for restraining tumor progression in prostate
      cancer. 

PMID- 24317510
TI  - An integrative analysis reveals functional targets of GATA6 transcriptional
      regulation in gastric cancer.
AB  - Lineage-restricted transcription factors (TFs) are frequently mutated or
      overexpressed in cancer and contribute toward malignant behaviors; however, the
      molecular bases of their oncogenic properties are largely unknown. As TF
      activities are difficult to inhibit directly with small molecules, the genes and
      pathways they regulate might represent more tractable targets for drug therapy.
      We studied GATA6, a TF gene that is frequently amplified or overexpressed in
      gastric, esophageal and pancreatic adenocarcinomas. GATA6-overexpressing gastric
      cancer cell lines cluster in gene expression space, separate from non
      overexpressing lines. This expression clustering signifies a shared pathogenic
      group of genes that GATA6 may regulate through direct cis-element binding. We
      used chromatin immunoprecipitation and sequencing (ChIP-seq) to identify GATA6
      bound genes and considered TF occupancy in relation to genes that respond to
      GATA6 depletion in cell lines and track with GATA6 mRNA (synexpression groups) in
      primary gastric cancers. Among other cellular functions, GATA6-occupied genes
      control apoptosis and govern the M-phase of the cell cycle. Depletion of GATA6
      reduced the levels of the latter transcripts and arrested cells in G2 and M
      phases of the cell cycle. Synexpression in human tumor samples identified likely
      direct transcriptional targets substantially better than consideration only of
      transcripts that respond to GATA6 loss in cultured cells. Candidate target genes
      responded to the loss of GATA6 or its homolog GATA4 and even more to the
      depletion of both proteins. Many GATA6-dependent genes lacked nearby binding
      sites but several strongly dependent, synexpressed and GATA6-bound genes encode
      TFs such as MYC, HES1, RARB and CDX2. Thus, many downstream effects occur
      indirectly through other TFs and GATA6 activity in gastric cancer is partially
      redundant with GATA4. This integrative analysis of locus occupancy, gene
      dependency and synexpression provides a functional signature of GATA6
      overexpressing gastric cancers, revealing both limits and new therapeutic
      directions for a challenging and frequently fatal disease. 

PMID- 24317513
TI  - Contribution of an alveolar cell of origin to the high-grade malignant phenotype
      of pregnancy-associated breast cancer.
AB  - Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy
      or up to 5 years following parturition, and are usually high-grade, connective
      tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is
      known about the cellular origin of PABCs or the mechanisms by which PABCs are
      initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the
      mammary epithelium of our previously reported MMTV-tva transgenic mice, we
      detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors
      during pregnancy and lactation. These high-grade and stroma-rich tumors were less
      frequent in involuted mice or in age-matched nulliparous mice. More importantly,
      by generating a WAP-tva transgenic line for expression of ErbB2 selectively in
      WAP(+) mammary alveolar cells, we found that tumors had similar morphological
      phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative),
      irrespective of the time since pregnancy and even in the absence of pregnancy.
      These data suggest that PABCs arise preferentially from an alveolar cell
      population that expands during pregnancy and lactation. This somatic mouse model
      may also be useful for preclinical testing of new prophylactic and therapeutic
      strategies against PABC. 

PMID- 24317512
TI  - CDK/CK1 inhibitors roscovitine and CR8 downregulate amplified MYCN in
      neuroblastoma cells.
AB  - To understand the mechanisms of action of (R)-roscovitine and (S)-CR8, two
      related pharmacological inhibitors of cyclin-dependent kinases (CDKs), we applied
      a variety of '-omics' techniques to the human neuroblastoma SH-SY5Y and IMR32
      cell lines: (1) kinase interaction assays, (2) affinity competition on
      immobilized broad-spectrum kinase inhibitors, (3) affinity chromatography on
      immobilized (R)-roscovitine and (S)-CR8, (4) whole genome transcriptomics
      analysis and specific quantitative PCR studies, (5) global quantitative
      proteomics approach and western blot analysis of selected proteins. Altogether,
      the results show that the major direct targets of these two molecules belong to
      the CDKs (1,2,5,7,9,12), DYRKs, CLKs and CK1s families. By inhibiting CDK7, CDK9
      and CDK12, these inhibitors transiently reduce RNA polymerase 2 activity, which
      results in downregulation of a large set of genes. Global transcriptomics and
      proteomics analysis converge to a central role of MYC transcription factors
      downregulation. Indeed, CDK inhibitors trigger rapid and massive downregulation
      of MYCN expression in MYCN-amplified neuroblastoma cells as well as in nude mice
      xenografted IMR32 cells. Inhibition of casein kinase 1 may also contribute to the
      antitumoral activity of (R)-roscovitine and (S)-CR8. This dual mechanism of
      action may be crucial in the use of these kinase inhibitors for the treatment of
      MYC-dependent cancers, in particular neuroblastoma where MYCN amplification is a
      strong predictor factor for high-risk disease. 

PMID- 24317515
TI  - Analyzing abundance of mRNA molecules with a near-infrared fluorescence
      technique.
AB  - This study describes a simple method for analyzing the abundance of mRNA
      molecules in a total DNA sample. Due to the dependence on the near-infrared
      fluorescence technique, this method is named near-infrared fluorescence gene
      expression detection (NIRF-GED). The procedure has three steps: (1) isolating
      total RNA from detected samples and reverse-transcription into cDNA with a biotin
      labeled oligo dT; (2) hybridizing cDNA to oligonucleotide probes coupled to a 96
      well microplate; and (3) detecting biotins with NIRF-labeled streptavidin. The
      method was evaluated by performing proof-in-concept detections of absolute and
      relative expressions of housekeeping and NF-kappaB target genes in HeLa cells. As
      a result, the absolute expression of three genes, Ccl20, Cxcl2, and Gapdh, in TNF
      alpha-uninduced HeLa cells was determined with a standard curve constructed on
      the same microplate, and the relative expression of five genes, Ccl20, Cxcl2, Il
      6, STAT5A, and Gapdh, in TNF-alpha-induced and -uninduced HeLa cells was measured
      by using NIRF-GED. The results were verified by quantitative PCR (qPCR) and DNA
      microarray detections. The biggest advantage of NIRF-GED over the current
      techniques lies in its independence of exponential or linear amplification of
      nucleic acids. Moreover, NIRF-GED also has several other benefits, including high
      sensitivity as low as several fmols, absolute quantification in the range of 9 to
      147 fmols, low cDNA consumption similar to qPCR template, and the current medium
      throughput in 96-well microplate format and future high throughput in DNA
      microarray format. NIRF-GED thus provides a new tool for analyzing gene
      transcripts and other nucleic acid molecules. 

PMID- 24317516
TI  - Detection of trace nitrite in waters using a QDs-based chemiluminescence analysis
      system.
AB  - In the present work, a novel flow-injection chemiluminescence method based on
      CdTe quantum dots (QDs) was developed for the determination of nitrite. Weak
      chemiluminescence (CL) signals were observed from a CdTe QDs-H2O2 system under
      basic conditions. The addition of a trace amount of hemoglobin (Hb) caused the CL
      from the CdTe QDs-H2O2 system to increase substantially. In the presence of
      nitrite, the ferrous Hb reacted with the nitrate to form ferric Hb and NO. The NO
      then bound to ferrous Hb to generate iron nitrosyl Hb. As a result, the CL signal
      from the CdTe QDs-H2O2-Hb system was quenched. Thus, a flow-injection CL
      analytical system for the determination of trace nitrite was established. Under
      optimum conditions, there was a good linear relationship between CL intensity and
      the concentration of nitrite in the range 1.0 * 10(-9) to 8.0 * 10(-7) mol L(-1)
      (R (2) = 0.9957). The limit of detection for nitrite using this system was 3.0 *
      10(-10) mol L(-1) (S/N = 3). This method was successfully applied to detect
      nitrite in water samples. 

PMID- 24317514
TI  - Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung
      adenocarcinoma.
AB  - Mice in which lung epithelial cells can be induced to express an oncogenic
      Kras(G12D) develop lung adenocarcinomas in a manner analogous to humans. A myriad
      of genetic changes accompany lung adenocarcinomas, many of which are poorly
      understood. To get a comprehensive understanding of both the transcriptional and
      post-transcriptional changes that accompany lung adenocarcinomas, we took an
      omics approach in profiling both the coding genes and the non-coding small RNAs
      in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis
      of Kras(G12D) tumors from F1 hybrid mice revealed features specific to tumor
      samples. This includes the repression of a network of GTPase-related genes
      (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated
      cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide
      polymorphisms revealed not only a change in expression of Cd22 but also that its
      expression became allele specific in tumors. The most salient finding, however,
      came from small RNA sequencing of the tumor samples, which revealed that a
      cluster of ~53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome
      12qF1 was markedly and consistently increased in tumors. Activation of this locus
      occurred specifically in sorted tumor-originating cancer cells. Interestingly,
      the 12qF1 RNAs were repressed in cultured Kras(G12D) tumor cells but reactivated
      when transplanted in vivo. These microRNAs have been implicated in stem cell
      pleuripotency and proteins targeted by these microRNAs are involved in key
      pathways in cancer as well as embryogenesis. Taken together, our results strongly
      imply that these microRNAs represent key targets in unraveling the mechanism of
      lung oncogenesis. 

PMID- 24317517
TI  - Matrix-assisted laser desorption/ionization mass spectrometry imaging of
      cardiolipins in rat organ sections.
AB  - Cardiolipin (CL) is a class of phospholipid tightly associated with the
      mitochondria functions and a prime target of oxidative stress. Peroxidation of CL
      dissociates its bound cytochrome C, a phenomenon that reflects oxidative stress
      sustained by the organ and a trigger for the intrinsic apoptotic pathway.
      However, CL distribution in normal organ tissues has yet to be documented. Fresh
      rat organs were snap-frozen, cut into cryosections that were subsequently
      desalted with ammonium acetate solution, and vacuum-dried. CL distribution in
      situ was determined using matrix-assisted laser desorption/ionization mass
      spectrometry imaging (MALDI-MSI) technique on sections sublimed with 2,5
      dihydroxybenzoic acid. CL images in rat cardiac ventricular section showed a
      homogeneous distribution of a single m/z 1447.9 ion species that was confirmed as
      the (18:2)4 CL by tandem mass spectrometry. The presence of low abundant
      (18:2)3(18:1) CL with the bulk (18:2)4 CL in quadriceps femoris rendered the
      muscle CL exhibiting a slightly deviated isotopic pattern from that of cardiac
      muscle. In rat liver, MALDI-MSI unveiled three CL-containing mass ranges, each
      with a unique in situ distribution pattern. Co-registration of the CL ion images
      with its stained liver section image further revealed the association of CLs in
      each mass range with the functional zones in the liver parenchyma and suggests
      the participation of in situ CLs with localized hepatic functions such as
      oxidation, conjugation, and detoxification. The advances in CL imaging offer an
      approach with molecular accuracy to reveal potentially dysregulated metabolic
      machineries in acute and chronic diseased states. 

PMID- 24317518
TI  - Determination of neurotransmitters and their metabolites using one- and two
      dimensional liquid chromatography with acidic potassium permanganate
      chemiluminescence detection.
AB  - High-performance liquid chromatography with chemiluminescence detection based on
      the reaction with acidic potassium permanganate and formaldehyde was explored for
      the determination of neurotransmitters and their metabolites. The
      neurotransmitters norepinephrine and dopamine were quantified in the left and
      right hemispheres of rat hippocampus, nucleus accumbens and prefrontal cortex,
      and the metabolites vanillylmandelic acid, 3,4-dihydrophenylacetic acid, 5
      hydroxyindole-3-acetic acid and homovanillic acid were identified in human urine.
      Under optimised chemiluminescence reagent conditions, the limits of detection for
      these analytes ranged from 2.5 * 10(-8) to 2.5 * 10(-7) M. For the determination
      of neurotransmitter metabolites in urine, a two-dimensional high-performance
      liquid chromatography (2D-HPLC) separation operated in heart-cutting mode was
      developed to overcome the peak capacity limitations of the one-dimensional
      separation. This approach provided the greater separation power of 2D-HPLC with
      analysis times comparable to conventional one-dimensional separations. 

PMID- 24317519
TI  - Progress in the determination of metalloids and non-metals by means of high
      resolution continuum source atomic or molecular absorption spectrometry. A
      critical review.
AB  - This work examines the new possibilities introduced with the arrival of
      commercially available high-resolution continuum source atomic absorption
      spectrometers for the determination of metalloids (B, Si, Ge, As, Se, Sb and Te)
      and non-metals (P, S, F, Cl, Br, I and N-based species), such as the improved
      potential to detect and correct for spectral overlaps and the strategies
      available to correct for matrix effects. In particular, and considering the
      increasing number of papers reporting on the use of molecular absorption
      spectrometry using graphite furnaces and flames as vaporizers, the work discusses
      in detail the advantages and limitations derived from the monitoring of molecular
      spectra from a practical point of view, in an attempt to guide future users of
      the technique. 

PMID- 24317520
TI  - Carbon nanotube poroshell silica as a novel stationary phase for fast HPLC
      analysis of monoclonal antibodies.
AB  - A new carbon nanotube porous silica poroshell stationary phase was developed. The
      chromatographic support was coated with ultrashort single-wall carbon nanotubes
      (SWCNTs) in a noncovalent way. It was demonstrated that the porous amino silica
      surface of the 300 NH2 poroshell column stabilized with 1-methyl-2-pyrrolidinone
      efficiently and stably adsorbed SWCNTs onto the chromatographic support. It was
      shown that this novel poroshell carbon nanotube (CNT) stationary phase was very
      useful for the HPLC separation of a series of monoclonal antibodies (mAbs) in a
      short analysis time (<3 min). The high-performance liquid chromatography (HPLC)
      method was validated and was successfully tested for the fast quantitative and
      qualitative control of chemotherapeutic bags fabricated in a hospital pharmacy. 

PMID- 24317521
TI  - A simplification and implementation of random-effects meta-analyses based on the
      exact distribution of Cochran's Q.
AB  - BACKGROUND: The random-effects (RE) model is the standard choice for meta
      analysis in the presence of heterogeneity, and the standard RE method is the
      DerSimonian and Laird (DSL) approach, where the degree of heterogeneity is
      estimated using a moment-estimator. The DSL approach does not take into account
      the variability of the estimated heterogeneity variance in the estimation of
      Cochran's Q. Biggerstaff and Jackson derived the exact cumulative distribution
      function (CDF) of Q to account for the variability of tau^2. OBJECTIVES: The
      first objective is to show that the explicit numerical computation of the density
      function of Cochran's Q is not required. The second objective is to develop an R
      package with the possibility to easily calculate the classical RE method and the
      new exact RE method. METHODS: The novel approach was validated in extensive
      simulation studies. The different approaches used in the simulation studies,
      including the exact weights RE meta-analysis, the I2 and tau2 estimates together
      with their confidence intervals were implemented in the R package metaxa.
      RESULTS: The comparison with the classical DSL method showed that the exact
      weights RE meta-analysis kept the nominal type I error level better and that it
      had greater power in case of many small studies and a single large study. The
      Hedges RE approach had inflated type I error levels. Another advantage of the
      exact weights RE meta-analysis is that an exact confidence interval for tau2 is
      readily available. The exact weights RE approach had greater power in case of few
      studies, while the restricted maximum likelihood (REML) approach was superior in
      case of a large number of studies. Differences between the exact weights RE meta
      analysis and the DSL approach were observed in the re-analysis of real data sets.
      Application of the exact weights RE meta-analysis, REML, and the DSL approach to
      real data sets showed that conclusions between these methods differed.
      CONCLUSIONS: The simplification does not require the calculation of the density
      of Cochran's Q, but only the calculation of the cumulative distribution function,
      while the previous approach required the computation of both the density and the
      cumulative distribution function. It thus reduces computation time, improves
      numerical stability, and reduces the approximation error in meta-analysis. The
      different approaches, including the exact weights RE meta-analysis, the I2 and
      tau2 estimates together with their confidence intervals are available in the R
      package metaxa, which can be used in applications.

PMID- 24317522
TI  - Synthesis, antimycobacterial activity and in vitro cytotoxicity of 5-chloro-N
      phenylpyrazine-2-carboxamides.
AB  - 5-Chloropyrazinamide (5-Cl-PZA) is an inhibitor of mycobacterial fatty acid
      synthase I with a broad spectrum of antimycobacterial activity in vitro. Some N
      phenylpyrazine-2-carboxamides with different substituents on both the pyrazine
      and phenyl core possess significant in vitro activity against Mycobacterium
      tuberculosis. To test the activity of structures combining both the 5-Cl-PZA and
      anilide motifs a series of thirty 5-chloro-N-phenylpyrazine-2-carboxamides with
      various substituents R on the phenyl ring were synthesized and screened against
      M. tuberculosis H37Rv, M. kansasii and two strains of M. avium. Most of the
      compounds exerted activity against M. tuberculosis H37Rv in the range of MIC =
      1.56-6.25 ug/mL and only three derivatives were inactive. The phenyl part of the
      molecule tolerated many different substituents while maintaining the activity. In
      vitro cytotoxicity was decreased in compounds with hydroxyl substituents,
      preferably combined with other hydrophilic substituents. 5-Chloro-N-(5-chloro-2
      hydroxyphenyl)pyrazine-2-carboxamide (21) inhibited all of the tested strains
      (MIC = 1.56 ug/mL for M. tuberculosis; 12.5 ug/mL for other strains). 4-(5
      Chloropyrazine-2-carboxamido)-2-hydroxybenzoic acid (30) preserved good activity
      (MIC = 3.13 ug/mL M. tuberculosis) and was rated as non-toxic in two in vitro
      models (Chinese hamster ovary and renal cell adenocarcinoma cell lines; SI = 47
      and 35, respectively). 

PMID- 24317523
TI  - Synthesis, structures and properties of two metal-organic coordination polymers
      derived from manganese(IotaIota), thiabendazole and polydentate carboxylic acids.
AB  - Two novel binuclear Mn(II) metal-organic coordination complexes
      [Mn2(TBZ)2(CDC)(C2O4)]n (1), {[Mn2(TBZ)2(BDC)(0.5)(BTC)(H2O)2].ET}n (2), (where
      TBZ = thiabendazole, H2CDC = trans-1,4-cyclohexanedicarboxylic acid, H2C2O4 =
      oxalic acid, H3BTC = 1,3,5-benzenetricarboxylic acid, ET = ethanol, H2BDC = 1,4
      benzenedicarboxylate) have been hydrothermally synthesized and characterized by
      elemental analysis, IR spectroscopy, thermogravimetric analysis, electrochemical
      analysis and single crystal X-ray diffraction. The X-ray structure analysis
      reveals that 1 is s two-dimensional layer and 2 is s one-dimensional chain. In
      complex 1, it reveals 2-D layers composed of multi-(bidentate) bridging ligands
      (CDC and C2O4), and in 2, the coordinated BTC ligands adopt a monodentate mode
      and with BDC ligands adopt alternately chelating Mn1 and Mn2 bridges into 1-D
      chains. The 3-D structures of the two complexes are stabilized by pi-pi stacking
      interactions and hydrogen bonds.

PMID- 24317524
TI  - Synthesis, spectroscopic and semiempirical studies of new quaternary
      alkylammonium conjugates of sterols.
AB  - New quaternary alkylammonium conjugates of steroids were obtained by two step
      reaction of sterols (ergosterol, cholesterol, dihydrocholesterol) with
      bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with
      a long chain tertiary alkylamine. The structures of products were confirmed by
      spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry and PM5
      semiempirical methods. The pharmacotherapeutic potential of synthesized compounds
      has been estimated on the basis of Prediction of Activity Spectra for Substances
      (PASS). 

PMID- 24317525
TI  - Multiplexed analysis of cage and cage free chicken egg fatty acids using stable
      isotope labeling and mass spectrometry.
AB  - Binary stable isotope labeling couple with LC-ESI-MS has been used as a powerful
      non-targeted approach for the relative quantification of lipids, amino acids, and
      many other important metabolite classes. A multiplexed approach using three or
      more isotopic labeling reagents greatly reduces analytical run-time while
      maintaining excellent sensitivity and reproducibility. Three isotopic cholamine
      labeling reagents have been developed to take advantage of the pre-ionized
      character of cholamine, for ESI, and the ease by which stable isotopes can be
      incorporated into the cholamine structure. These three cholamine labeling
      reagents have been used to relatively quantify three fatty acid samples
      simultaneously. The quantification resulted in the observation of 12 fatty acids
      that had an average absolute error of 0.9% and an average coefficient of
      variation of 6.1%. Caged versus cage-free isotope labeling experiments showed
      that cage-free eggs have an increased level of omega-3 fatty acids as compared to
      caged eggs. This multiplexed fatty acid analysis provides an inexpensive and
      expedited tool for broad-based lipid profiling that will further aid discoveries
      in the mechanisms of fatty acid action in cells. 

PMID- 24317526
TI  - Effects of Aronia melanocarpa constituents on biofilm formation of Escherichia
      coli and Bacillus cereus.
AB  - Many bacteria growing on surfaces form biofilms. Adaptive and genetic changes of
      the microorganisms in this structure make them resistant to antimicrobial agents.
      Biofilm-forming organisms on medical devices can pose serious threats to human
      health. Thus, there is a need for novel prevention and treatment strategies. This
      study aimed to evaluate the ability of Aronia melanocarpa extracts, subfractions
      and compounds to prevent biofilm formation and to inhibit bacterial growth of
      Escherichia coli and Bacillus cereus in vitro. It was found that several aronia
      substances possessed anti-biofilm activity, however, they were not toxic to the
      species screened. This non-toxic inhibition may confer a lower potential for
      resistance development compared to conventional antimicrobials. 

PMID- 24317527
TI  - Synthesis and biological activity of 3-[phenyl(1,3-thiazol-2-yl)-amino]propanoic
      acids and their derivatives.
AB  - New N,N-disubstituted beta-amino acids and their derivatives with thiazole,
      aromatic, and heterocyclic substituents were synthesized from N-phenyl-N
      thiocarbamoyl-beta-alanine by the Hantzsch method; derivatives with hydrazone
      fragments were also obtained. Some of the synthesized compounds exhibited
      discrete antimicrobial activity, and 3-[(4-oxo-4,5-dihydro-1,3-thiazol-2
      yl)(phenyl)amino]propanoic acid was found to promote rapeseed growth and to
      increase seed yield and oil content. 

PMID- 24317528
TI  - Helping Eve overcome ADAM: G-quadruplexes in the ADAM-15 promoter as new
      molecular targets for breast cancer therapeutics.
AB  - ADAM-15, with known zymogen, secretase, and disintegrin activities, is a
      catalytically active member of the ADAM family normally expressed in early
      embryonic development and aberrantly expressed in various cancers, including
      breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin,
      a soluble ligand for the HER2/neu receptor, leading to activation, increased
      motility, and proliferation. Targeted downregulation of both ADAM-15 and HER2/neu
      function synergistically kills breast cancer cells, but to date there are no
      therapeutic options for decreasing ADAM-15 function or expression. In this vein,
      we have examined a unique string of guanine-rich DNA within the critical core
      promoter of ADAM-15. This region of DNA consists of seven contiguous runs of
      three or more consecutive guanines, which, under superhelical stress, can relax
      from duplex DNA to form an intrastrand secondary G-quadruplex (G4) structure.
      Using biophysical and biological techniques, we have examined the G4 formation
      within the entire and various truncated regions of the ADAM-15 promoter, and
      demonstrate strong intrastrand G4 formation serving to function as a biological
      silencer element. Characterization of the predominant G4 species formed within
      the ADAM-15 promoter will allow for specific drug targeting and stabilization,
      and the further development of novel, targeted therapeutics. 

PMID- 24317529
TI  - Reduced expression of DENND2D through promoter hypermethylation is an adverse
      prognostic factor in squamous cell carcinoma of the esophagus.
AB  - Esophageal cancer ranks sixth in cancer mortality worldwide and patients with
      esophageal squamous cell carcinoma (ESCC) have a poor prognosis with a 5-year
      survival rate of less than 10%. Elucidation of the mechanisms of carcinogenesis
      and tumor progression in esophageal cancer is urgently required to develop
      targets for therapy and prognostic biomarkers. In the present study, the
      expression and regulatory mechanism of the differentially expressed in normal and
      neoplastic cells domain containing 2D (DENND2D), which is a regulator of Rab
      GTPases, were investigated to explore its potential as a tumor suppressor gene
      for ESCC. The level of DENND2D mRNA expression in ESCC cell lines and surgical
      specimens was determined using a quantitative real-time reverse transcription
      polymerase chain reaction assay, and the relationship between the expression
      levels of DENND2D mRNA and clinicopathological factors was evaluated. The
      expression and distribution of DENND2D were determined using
      immunohistochemistry. DNA methylation analysis was performed to determine the
      regulatory mechanism of DENND2D expression in ESCC. The level of DENND2D mRNA
      expression was reduced in 8/9 ESCC cell lines and in 59/65 surgical specimens,
      and the mean expression levels were significantly lower in cancerous tissues
      compared to corresponding normal tissues (p<0.001). The expression pattern of
      DENND2D protein and mRNA was consistent. Downregulation of DENND2D mRNA in ESCC
      tissues was identified as an independent prognostic factor in multivariate
      analysis (hazard ratio, 2.194; p=0.039). The DENND2D promoter was methylated in
      5/9 ESCC cell lines, and DNA demethylation reactivated DENND2D mRNA expression.
      Hypermethylation of DENND2D was frequently detected in ESCC tissues (64.6%) and
      was significantly associated with downregulation of DENND2D mRNA expression
      (P=0.008). Taken together, our data suggest that DENND2D is a candidate tumor
      suppressor gene that was inactivated by promoter hypermethylation in patients
      with ESCC and may serve as a novel biomarker of ESCC. 

PMID- 24317530
TI  - Heritability of a linear combination of traits.
AB  - The heritability, h I (2) , of a linear combination of phenotypes, I, when
      defined as the ratio of the variance of the genetic index, sigma g? (2) *, to the
      variance of the index, sigma I (2) , is shown to be different from the square of
      the correlation, r HI (2) , between the index and an arbitrary linear combination
      of genetic effects, H. The gain in H fror selection on I is shown to be
      proportional to h I (2) . bHg? for any index. 

PMID- 24317531
TI  - Observations on the genetic structure and mating system of ponderosa pine in the
      Colorado front range.
AB  - Variation of peroxidase enzymes is analyzed both in mature needle tissue and in
      open-pollinated seedling families of ponderosa pine, Pinus ponderosa, and is
      identified as being controlled by a single Mendelian locus. Variation at this
      locus, analyzed in 1, 386 individuals, is used in the analysis of population
      differentiation and the mating system. Significant variation of gene frequencies
      is detected over distances of several hundred meters, and is found to be
      associated with slopes of different aspects. Ponderosa pine is wind-pollinated,
      and an analysis of the mating system indicates that the level of outcrossing is
      greater than 90 %. Selection specific for different environments is evidently
      strong enough to overcome the homogenizing force of migration and produce
      population fissuring in ponderosa pine. 

PMID- 24317532
TI  - The level of free amino acids in erythrocytes of different breeds of hen.
AB  - The content of free amino acids was determined in erythrocytes of adult 'Leghorn'
      (Lg, 'White Rock' (WR) and 'Cornish' (Cr) hens, bred under identical conditions.
      The concentration of total amino acids was twice as high in the erythrocytes as
      in plasma, amounting to 396 MUm/100 ml, 424 MUm/100 ml and 475MUm/100 ml in
      'White Rock', 'Cornish' and 'Leghorn' hens, respectively.Significant differences
      were found in the ratio of basic amino acids to acidic amino acids. These values
      were 0.76, 1.75 and 3.19 in 'White Rick', 'Leghorn' and 'Cornish' hens,
      respectively; in the plasma of all 3 breeds the ratio was 1. Statistically
      significant interbreed differences were expressed more distinctly in erythrocyte
      than in plasma amino acid concentrations. For absolute concentrations the
      differences were significant in the case of 9 amino acids. 

PMID- 24317533
TI  - The gene of golden plumage colour linked with lower fertility in Mangurian Golden
      quail.
AB  - Relation between golden plumage colour and lowered fertility has been found in
      quails (Coturnix coturnix japonica). Golden colour of plumage is due to the
      presence of a single gene G, while its recessive alleles gg determine partridge
      like colour. Homozygotic birds of GG pattern die during incubation. 

PMID- 24317534
TI  - Genotypic and environmental variation in autumn-sown onions.
AB  - Seven onion cultivars of Japanese and European origin were evaluated in autumn
      sown trials, at six sites over two seasons. Within each season genotypic
      differences were detected for winter-kill, bolting, maturity time and yield. In
      general the Japanese cultivars showed consistently lower levels of bolting and
      winter-kill and earlier maturity relative to the European cultivars.
      Environmental effects were important with differences between seasons, sites and
      sowings recorded for most characters. It was concluded that the use of early and
      late August sowings would provide suitable screening environments for bolting and
      winter-kill respectively. There were also differences between genotypes in their
      linear response to environments as shown by joint regression analyses. 'Express
      Yellow O-X' (hybrid) showed least response to environments for bolting and winter
      kill and 'Senshyu semi-globe Yellow' gave the most consistent time to maturity
      over environments. 

PMID- 24317535
TI  - Selection studies in sugarcane (Saccharum sp. hybrids) : III. A method to
      determine sample size for the estimation of population variance.
AB  - An approximate method to determine sample size for the estimation of population
      variance, sigma(2), is given. The estimate of sigma(2) is denoted as s(2) . Based
      on the assumption of a normal distribution for (s(2)/sigma(2)-1), the sample size
      is approximately equal to 20,000 z(2) p,/k(2); where z is a standard normal
      deviate, p is the probability that Deltas(2) (= 100|s(2) - sigma(2)|/sigma(2)) is
      less than, or equal to, a critical value k, and k (measured as gDs(2)) is the
      desired precision of s(2) .The expected value of Deltas(2), with respect to
      sample size, and the expected cumulative frequencies of Deltas(2) over sample
      size for various k values are given. Their goodness of fit to the observed
      results was satisfactory except for populations that were different from normal.
      The observed values were taken from a study on four yield components in five
      sugarcane polycross progenies, grown in two contrasting environments over 2 years
      in three selection stages.The expected Deltas(2) was found to be independent of
      the population coefficient of variance. 

PMID- 24317536
TI  - Measuring the precision of genetic parameters by a simulation technique.
AB  - Approximate standard errors of genetic parameter estimates were obtained using a
      simulation technique and approximation formulae for a simple statistical model.
      The similarity of the corresponding estimates of standard errors from the two
      methods indicated that the simulation technique may be useful for estimating the
      precision of genetic parameter estimates for complex models or unbalanced
      population structures where approxi mation formulae do not apply. The method of
      generating simulation populations in the computer is outlined, and a technique of
      setting approximate confidence limits to heritability estimates is described. 

PMID- 24317537
TI  - Stability analysis over various filial generations in bread wheat.
AB  - Stability analysis on 7 parent varieties and all their possible crosses
      (excluding reciprocals) in generations F1 to F5 are reported. The regression
      coefficient (b) of the parents ranged from 0.66 ('Sonalika') to 1.34
      ('Kalyansona'). On the average the 'b' value was lower in F3 (.87) and F2 (.88)
      followed by F1 (1.04), F4 (1.06) and F5 (1.16). Phenotypic stability appeared to
      be associated with genetic constitution of the parents as well as level of
      heterozygosity and heterogeneity of the populations. Distinct differences were
      observed in general combining ability values for regression coefficients among
      the parents, indicating transmissibility of this trait. However, no such trend
      was observed for deviation mean squares. The data on yield and stability
      parameters showed that high mean yield is not necessarily associated with average
      regression, indicating the possibility of combining high mean yield with high
      stability. 

PMID- 24317538
TI  - Psychometric properties of the 'Skala Kepuasan Interaksi Perubatan-11' to measure
      patient satisfaction with physician-patient interaction in Malaysia.
AB  - BACKGROUND: Patient satisfaction influences the outcomes of the patient-physician
      encounter. OBJECTIVE: The objective of this study was to validate the Malay
      version patient satisfaction (MISS-21) questionnaire using a confirmatory
      validity approach. METHODS: A cross-sectional study was conducted involving 252
      patients attending primary health clinic, Hospital Universiti Sains Malaysia.
      Construct validity (convergent and discriminant) using confirmatory factor
      analysis and internal consistency were performed after the translation, content
      validity and face validity processes. Criterion validity was assessed using
      Pearson correlations with the scale of shared decision making 9-item
      questionnaire (SDMQ-9). The data was analysed using Analysis of Moment Structure
      version 19. RESULTS: A total of 252 (100%) outpatients responded to this study.
      The final model that consists of three domains with 11 items had a good fit; (chi
      (2) (df) = 65.805 (32), P < 0.001, Tucker-Lewis indices = 0.902, comparative fit
      index = 0.927, root mean square error of approximation = 0.061, standardized root
      mean square residual = 0.058). Composite reliability and average variance
      extracted of the domains ranged from 0.541 to 0.760 and 0.240 to 0.522,
      respectively. The SDMQ-9 had a moderate correlation with the total score of the
      final construct (r = 0.406, P <0.001). CONCLUSION: The study suggested that the
      three-factor model with 11 items of the Malay version MISS-21 could be used to
      assess patient satisfaction on patient-physician interaction in primary health
      care setting because it is acceptably valid, reliable and simple. The validated
      Malay version questionnaire was called as 'Skala Kepuasan Interaksi Perubatan
      11'.

PMID- 24317539
TI  - Comparison between electrofishing and snorkeling surveys to describe fish
      assemblages in Laurentian streams.
AB  - We evaluated the relative performance of electrofishing and visual surveys
      (snorkeling) for estimating the abundance of combinations of fish species and
      size classes in rivers. We also assessed the effect of environmental conditions
      on potential differences between the results obtained using these two sampling
      methods. Sampling sites were distributed in the Laurentian region of Quebec. Both
      methods were used while sections were blocked. Three snorkelers swam the river
      sections upstream while identifying and counting fish of each species and size
      classes. Three-pass electrofishing was performed in the same sites and abundances
      were estimated with a maximum likelihood depletion model. Greater abundances of
      fish were observed by snorkeling than by electrofishing at all sites. Snorkeling
      species richness was higher or equal to electrofishing richness in, respectively,
      60 % and 40 % of sampled sites. Differences in the fish communities observed by
      both sampling methods were not related to environmental conditions. The results
      of our work are therefore contrary to that of most published studies that
      suggested the use of electrofishing over visual surveys. This study highlights
      that conclusions derived from previous work on sampling gear comparisons may not
      be generalisable; rather survey methods might benefit from being selected based
      on fish community composition. 

PMID- 24317541
TI  - To skip or not to skip: that is the question for duchenne muscular dystrophy.

PMID- 24317540
TI  - The McClure and Weiss models of Fe-O2 bonding for oxyhemes, and the HbO2 + NO
      reaction.
AB  - For the Fe-O2(S = 0) linkages of oxyhemes, valence bond (VB) structures are re
      presented for the McClure [Fe(II)(S = 1) + O2(S = 1)], Pauling-Coryell [Fe(II)(S
      = 0) + O2*(S = 0)], and Weiss [Fe(III)(S = 1/2) + O2 (-)(S = 1/2)] models of
      bonding. The VB structures for the McClure and Weiss models are of the increased
      valence type, with more electrons participating in bonding than occur in their
      component Lewis structures. The Fe-O bond number and O-O bond order for the
      McClure structure are correlated with measured Fe-O and O-O bond lengths for
      oxymyoglobin. Back-bonding from O2(-) to Fe(III) of the Weiss structure gives a
      restricted form of the McClure structure. The McClure and Weiss increased-valence
      structures are used to provide VB formulations of mechanisms for the
      oxyhemoglobin + NO reaction. The products of these two formulations are Hb(+) and
      NO3(-) (where Hb is hemoglobin) and Hb(+) and OONO(-), respectively. Because
      Hb(+) and NO3(-) are the observed products, they provide an experimental
      procedure for distinguishing the McClure and Weiss models. It is also shown that
      the same type of agreement between McClure-type theory and experiment occurs for
      oxycoboglobin + NO, cytochrome P450 monooxygenases, and related hydrogen atom
      transfer reactions. In the appendices, the results of density functional theory
      and multireference molecular orbital calculations for oxyhemes are related to one
      formulation of the increased-valence wavefunction for the McClure model, and
      theory is presented for the calculation of approximate weights for the Lewis
      structures that are components of the McClure increased-valence structure.

PMID- 24317544
TI  - Psoriasis comprehensive care: an evaluation of a web site.
AB  - Psoriasis is a disease that affects many facets of life. Psoriasis patients have
      needs that cannot be addressed within the traditional consultation structure.
      Although the Internet provides a number of health resources, the quality of the
      information is variable, and many sites are not editorially independent. After
      reviewing the contents available on the Internet related to psoriasis, the staff
      of the psoriasis unit at San Cecilio University Hospital (Granada, Spain)
      developed a Web site to meet the needs of psoriasis patients. A group of 241
      patients who attended a follow-up visit to our psoriasis unit evaluated the Web
      site and provided feedback through an online survey. The result of the Web
      development process was the creation of "Psoriasis365"
      (https://sites.google.com/site/psoriasis365/). Overall, the Web site achieved
      high scores, the most popular section being "research." These results suggest
      that the Web site can complement the healthcare of psoriasis patients and is
      potentially useful for research purposes. 

PMID- 24317545
TI  - Does perioperative documentation transfer reliably?
AB  - In the complex and multiphasic perioperative process, there are many
      opportunities to transfer information between providers and settings. Previous
      studies have shown that information transfer and communication are vital to
      minimize risks in the perioperative setting. The aim of this study was to explore
      the incidence of failure to communicate vital information as the patient
      progressed through the six phases of the perioperative process. The systematic
      sample included ambulatory surgery patient records from one quarter. A failure to
      communicate rate was calculated as 10.2% for the 5586 entries. In the absence of
      a comprehensive electronic health record, a consistent method for information
      transfer must be used to minimize risks. 

PMID- 24317546
TI  - Why fundamentals of endoscopic surgery (FES)?

PMID- 24317549
TI  - Reliability of electrocardiographic surrogates of left ventricular mass in
      patients with chronic kidney disease.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) is a prevalent condition in chronic
      kidney disease (CKD) very often underdiagnosed and misdiagnosed.
      Electrocardiography (ECG) is an easily accessible LVH diagnostic tool. We
      evaluated the usefulness of commonly applied ECG criteria for LVH diagnosis in
      CKD patients. METHODS: Cross-sectional evaluation of 253 nondialysis-dependent
      CKD stages 3-5 patients (61 [53-67] years; 65% men). Left ventricular mass (LVM)
      was assessed by echocardiography (ECHO). ECG was performed to assess Cornell
      voltage and Sokolow-Lyon voltage and their products (Cornell product and Sokolow
      Lyon product, respectively). RESULTS: The prevalence of LVH ranged from 72 to 89%
      depending on ECHO criteria used. Cornell product showed the best correlation with
      ECHO-estimated LVM (rho = 0.41; P <0.001). Across sex-specific tertiles of ECHO
      LVM, ECG criteria increased and patients were more often hypertensive, obese,
      fluid overloaded, inflamed, and with higher albuminuria. Cornell product showed
      the strongest association with ECHO-LVM in crude and adjusted regression models,
      and the higher predictive performance for all the ECHO-based LVH definitions.
      However, when applying literature-based ECG cut-offs for LVH diagnosis, Sokolow
      Lyon product showed a higher specificity. The agreement between ECG criteria cut
      offs and ECHO-based definitions of LVH was in general poor, and the number of
      patients reclassified correctly by ECHO ranged from 77 to 94%. CONCLUSION: Our
      data suggest that ECG alone is a weak indicator of LVH, and do not support its
      routine use as a unique tool in the screening of LVH in CKD patients. Further
      studies are needed to confirm these results and to try establishing adequate cut
      offs for LVH diagnosis in this population.

PMID- 24317547
TI  - Improved insulin sensitivity after gastric bypass correlates with decreased total
      body fat, but not with changes in free fatty acids.
AB  - BACKGROUND: Increased plasma free fatty acids (FFAs) are considered one of the
      key elements in the pathogenesis of insulin resistance (IR) and type 2 diabetes
      (T2DM). We hypothesize that, in diabetic patients undergoing laparoscopic Roux-en
      Y gastric bypass (LRYGB), a postoperative decrease in FFA will correlate with
      improved insulin sensitivity (Si). METHODS: A total of 30 obese [body mass index
      ((BMI) >35 kg/m(2)] patients with a diagnosis of T2DM were studied preoperatively
      and 12 months after LRYGB in a prospective cohort study. Collected data included
      intravenous glucose tolerance test (IVGTT), total body composition by dual-energy
      X-ray absorptiometry and plasma levels of FFA. Si analysis from the IVGTT was
      estimated from minimal model analysis. Pre- and postoperative variables were
      compared using a paired sample t test. Relationships between changes in variables
      were determined with Pearson's correlation test. RESULTS: Twelve months after
      LRYGB the study population showed a significant decrease in BMI (p = 0.001), FFA
      (p = 0.03), and total body fat (p = 0.03), with an increase in Si (p = 0.001).
      Postoperative changes in Si significantly correlated (Pearson's r = -0.53, p =
      0.01) with change in total body fat, but not with changes in plasma FFA
      (Pearson's r = -0.22, p = 0.31). CONCLUSIONS: Our study challenges the notion
      that IR is mediated to a significant degree by changes in plasma FFA
      concentration. Instead, changes in adiposity and consequently changes in
      adipokine release can be the key players in determining remission of T2DM after
      LRYGB.

PMID- 24317550
TI  - Elevated systolic blood pressure during recovery from exercise and the risk of
      sudden cardiac death.
AB  - OBJECTIVE: The value of SBP during exercise and recovery period as a risk marker
      for sudden cardiac death (SCD) is not known. Thus, we assessed the association of
      SBP during recovery from exercise testing with the risk of SCD. METHODS: SBP was
      measured every 2 min during and at 2 min after a progressive cycle ergometer
      exercise in a representative sample of 2366 men (aged 42-61 years). During an
      average follow-up period of 18.9 years, a total of 180 SCDs occurred. RESULTS:
      SBP during recovery from exercise was associated with the risk of SCD (hazard
      ratio 1.24, 95% confidence interval 1.06-1.45, P=0.007 for 1 SD increment), after
      adjustment for age, risk factors and exercise test findings. Men with elevated
      SBP of over 195 mmHg at 2 min recovery from exercise had a 1.74-fold (95%
      confidence interval 1.18-2.54, P=0.005) risk of an SCD as compared to those with
      SBP less than 170 mmHg, after adjustment for age, risk factors and other exercise
      test findings. However, after further adjustment for resting SBP, the association
      between SBP at 2 min recovery from exercise and the risk of SCD became non
      significant. CONCLUSION: This study shows that SBP during recovery phase from
      exercise is related to the risk of SCD, although its prognostic value is limited
      in conjunction with the assessment of resting SBP in the general male population.

PMID- 24317551
TI  - Dimensional reductions of a cardiac model for effective validation and
      calibration.
AB  - Complex 3D beating heart models are now available, but their complexity makes
      calibration and validation very difficult tasks. We thus propose a systematic
      approach of deriving simplified reduced-dimensional models, in "0D"-typically, to
      represent a cardiac cavity, or several coupled cavities-and in "1D"-to model
      elongated structures such as muscle samples or myocytes. We apply this approach
      with an earlier-proposed 3D cardiac model designed to capture length-dependence
      effects in contraction, which we here complement by an additional modeling
      component devised to represent length-dependent relaxation. We then present
      experimental data produced with rat papillary muscle samples when varying preload
      and afterload conditions, and we achieve some detailed validations of the 1D
      model with these data, including for the length-dependence effects that are
      accurately captured. Finally, when running simulations of the 0D model pre
      calibrated with the 1D model parameters, we obtain pressure-volume indicators of
      the left ventricle in good agreement with some important features of cardiac
      physiology, including the so-called Frank-Starling mechanism, the End-Systolic
      Pressure-Volume Relationship, as well as varying elastance properties. This
      integrated multi-dimensional modeling approach thus sheds new light on the
      relations between the phenomena observed at different scales and at the local
      versus organ levels. 

PMID- 24317553
TI  - Urinary functional outcomes in female neobladder patients.
AB  - PURPOSE: The ratio between orthotopic and non-orthotopic diversions in women is
      far lower than in male patients. Data on urinary function in female patients with
      neobladders are therefore sparse. METHODS: We investigated the urinary function
      of female neobladder patients utilizing the Bladder Cancer Index, a validated and
      reliable health-related quality-of-life (HRQOL) questionnaire. Furthermore, we
      tried to identify preoperative factors that may influence functional results. All
      living female patients with an orthotopic neobladder (N = 82) from the University
      of Southern California Bladder Cancer Database were sent a questionnaire
      including the University of Michigan Bladder Cancer Index. Univariate analyses
      were performed using the Kruskal-Wallis test followed by a multivariate stepwise
      regression model. RESULTS: Fifty-six patients (68.3%) responded and were included
      in the analysis. Thirty-five (62.5%) of these patients had to catheterize their
      neobladder to a certain amount, while 25 patients (44.6%) depend on
      catheterization to empty their neobladder. Univariate analyses showed that
      patient age (>65 years) was the only variable associated with a statistically
      significant lower rate of neobladder catheterization. Better urinary bother
      scores were associated with organ-confined disease (p = 0.038) and education
      level (p = 0.01). However, these variables were not significant in a multivariate
      stepwise linear regression model. CONCLUSION: Considerably more women require
      urinary catheterization to void than previously reported. In this study,
      representing the largest investigated cohort in this topic, we were unable to
      identify any predictors of this outcome or any other urinary HRQOL in this
      cohort.

PMID- 24317552
TI  - Activation and intermuscular coherence of distal arm muscles during proximal
      muscle contraction.
AB  - In the human upper extremity (UE), unintended effects of proximal muscle
      activation on muscles controlling the hand could be an important aspect of motor
      control due to the necessary coordination of distal and proximal segments during
      functional activities. This study aimed to elucidate the effects of concurrent
      activation of elbow muscles on the coordination between hand muscles performing a
      grip task. Eleven healthy subjects performed precision grip tasks while a
      constant extension or flexion moment was applied to their elbow joints, inducing
      a sustained submaximal contraction of elbow muscles to counter the applied
      torque. Activation of four hand muscles was measured during each task condition
      using surface electromyography (EMG). When concurrent activation of elbow muscles
      was induced, significant changes in the activation levels of the hand muscles
      were observed, with greater effects on the extrinsic finger extensor (23.2 %
      increase under 30 % elbow extensor activation; p = 0.003) than extrinsic finger
      flexor (14.2 % increase under 30 % elbow flexor activation; p = 0.130). Elbow
      muscle activation also induced involuntary changes in the intrinsic thumb flexor
      activation (44.6 % increase under 30 % elbow extensor activation; p = 0.005). EMG
      EMG coherence analyses revealed that elbow muscle activation significantly
      reduced intermuscular coherence between distal muscle pairs, with its greatest
      effects on coherence in the beta-band (13-25 Hz) (average of 17 % decrease under
      30 % elbow flexor activation). The results of this study provide evidence for
      involuntary, muscle-specific interactions between distal and proximal UE muscles,
      which may contribute to UE motor performance in health and disease.

PMID- 24317555
TI  - Letter to the editor re: Comino, I., et al. Nutrients 2013, 5, 4250-4268.

PMID- 24317554
TI  - Salty taste acuity is affected by the joint action of alphaENaC A663T gene
      polymorphism and available zinc intake in young women.
AB  - Salty taste perception affects salt intake, of which excess amounts is a major
      public health concern. Gene polymorphisms in salty taste receptors, zinc status
      and their interaction may affect salty taste perception. In this study, we
      examined the relationships among the alpha-epithelial sodium channel (alphaENaC)
      A663T genotype, zinc intake, and salty taste perception including salty taste
      acuity and preference in healthy young adults. The alphaENaC A663T genotype was
      determined by the PCR-restriction fragment length polymorphism in 207 adults.
      Zinc intake was examined by one 24-h recall and a two-day dietary record. Salty
      taste acuity and preference were determined by measuring the salty taste
      recognition threshold and the preferred salinity of beansprout soup,
      respectively. Men had significantly higher thresholds and preferences for salty
      taste than women did (p < 0.05). In women, the salty taste threshold was
      significantly lower in the highest tertile of available zinc intake than in the
      lowest tertile (12.2 mM and 17.6 mM, respectively, p = 0.02). Interestingly, a
      significant inverse association between available zinc intake and salty taste
      threshold was found only in women with alphaENaC AA homozygotes (beta = -0.833, p
      = 0.02), and no such association was found in T663 allele carriers. The salty
      taste preference was not associated with the alphaENaC A663T genotype or
      available zinc intake in either sex. In conclusion, our data suggest that gene
      nutrient interactions between the alphaENaC A663T genotype and available zinc
      intake play a role in determining the salty taste acuity in young women. 

PMID- 24317557
TI  - In vitro biomechanical comparison of the effects of cerclage wires, an
      intramedullary pin and the combination thereof on an oblique osteotomy of the
      canine tibia.
AB  - OBJECTIVE: To compare the in vitro biomechanical effects of single loop cerclage
      wires, an intramedullary pin and the combination thereof as applied to an oblique
      mid-diaphyseal osteotomy of canine tibiae. METHODS: Three groups of nine bones
      with long oblique osteotomies were repaired with the following methods: 1) Three
      single loop cerclage wires and a transcortical skewer pin, 2) intramedullary
      pinning with a smooth Steinmann pin, and 3) a combination of both methods. The
      repaired constructs were tested in a single cycle four-point-bending test to
      failure. Load displacement curves were drawn and the following parameters were
      calculated or extrapolated: Stiffness, load at yield, and force resisted at 2 mm
      actuator displacement. The latter was determined to demonstrate the difference in
      the amount of energy absorbed between the different groups. RESULTS: The
      stiffness and force resisted at 2 mm displacement of the groups with cerclage
      wires were significantly higher than the group with an intramedullary pin alone
      (p <=0.05). The differences in stiffness (p = 0.15) and force required at 2 mm
      displacement (p = 0.56) between cerclage wires and the combination of cerclage
      wires and intramedullary pins were not significant. CLINICAL RELEVANCE: Cerclage
      wire repair results in higher stiffness than repair with an intramedullary pin.
      When cerclage wires are combined with an intramedullary pin, the intramedullary
      pin does not provide protection to the cerclage wire repair and the wires or the
      bone under the wires has to fail before the pin resists significant load.

PMID- 24317558
TI  - Wavelength dependence of photomovement in desmids.
AB  - The action spectra of phototaxis, photokinesis, and photophobic response of
      Cosmarium cucumis, C. botrytis, C. margaritiferum, and Micrasterias denticulata
      show peaks in the blue (about 440 nm) and red (about 670 nm) spectral regions and
      thus indicate the involvement of photosynthetic pigments. According to the
      differences in the action spectra, light-induced movement responses may be linked
      with photosynthesis in different ways. Results with population methods have been
      supported by time-lapse microcinematography. 

PMID- 24317556
TI  - Changes in blood pressure and lipid levels in young women consuming a vitamin D
      fortified skimmed milk: a randomised controlled trial.
AB  - Vitamin D exerts a variety of extra-skeletal functions. AIM: to know the effects
      of the consumption of a vitamin D-fortified skimmed milk on glucose, lipid
      profile, and blood pressure in young women. METHODS: a randomised, placebo
      controlled, double-blind parallel-group trial of 16 weeks duration was conducted
      in young women with low iron stores who consumed a skimmed milk fortified with
      iron and 200 IU/day (5 MUg) of vitamin D (D-fortified group, n = 55), or a
      placebo without vitamin D (D-placebo group, n = 54). A reference group (n = 56)
      of iron-sufficient women was also recruited. RESULTS: baseline serum 25
      hydroxyvitamin D was inversely correlated with total-cholesterol (r = -0.176, p =
      0.023) and low density lipoprotein-cholesterol (LDL-chol) (r = -0.176, p =
      0.024). During the assay, LDL-cholesterol increased in the D-placebo group (p =
      0.005) while it tended to decrease in the D-fortified group (p = 0.07). Neither
      group displayed changes in total-cholesterol, high density lipoprotein
      cholesterol (HDL-chol), triglycerides or glucose levels. Systolic (p = 0.017) and
      diastolic (p = 0.010) blood pressure decreased during the assay in the D
      fortified group without significant differences compared to the D-placebo.
      CONCLUSION: consumption of a dairy product fortified with vitamin D reduces
      systolic and diastolic blood pressure but does not change lipid levels in young
      women.

PMID- 24317559
TI  - Chloroplast phenylalanine ammonia-lyase from spinach leaves : Evidence for light
      mediated regulation via the ferredoxin/Thioredoxin system.
AB  - Phenylalanine ammonia-lyase (PAL) from spinach (Spinacia oleracea L.) leaves was
      resolved into three forms by diethyl-aminoethyl(DEAE)-cellulose chromatography.
      Two forms were found in isolated chloroplasts, and the third form (the major
      component) was located outside of the chloroplasts. One of the chloroplast forms
      of the enzyme (designated the regulatory form) was activated by reduced
      thioredoxin. Neither the other chloroplast form nor the extra-chloroplast form
      showed a response to thioredoxin. After further purification by hydroxyapatite
      column chromatography and gel filtration, the regulatory form of chloroplast PAL
      was stimulated approximately 3-fold by thioredoxin reduced either photochemically
      by chloroplast membranes, via ferredoxin and ferredoxin-thioredoxin reductase, or
      chemically by dithiothreitol. Once activated, the enzyme required an added
      oxidant for deactivation. Physiological oxidants-oxidized glutathione (GSSG) and
      dehydroascorbate-as well as nonphysiological oxidants-sodium tetrathionate and
      diamide-were effective in deactivation. The results indicate that chloroplast PAL
      is regulated by light via the ferredoxin/thioredoxin system in a manner similar
      to that described for regulatory enzymes of CO2 assimilation. The extra
      chloroplast form of the enzyme, by contrast, appears to be regulated by light via
      the earlier-described phytochrome-linked system. 

PMID- 24317560
TI  - Metabolic regulation of carbon flux during C4 photosynthesis : II. In situ
      evidence for reffixation of photorespiratory CO2 by C 4 phosphoenolpyruvate
      carboxylase.
AB  - The potential for glycolate and glycine metabolism and the mechanism of
      refixation of photorespiratory CO2 in leaves of C4 plants were studied by
      parallel inhibitor experiments with thin leaf slices, different leaf cell types
      and isolated mitochondria of C3 and C4 Panicum species. CO2 evolution by leaf
      slices of P. bisulcatum, a C3 species, fed glycolate or glycine was light
      independent and O2-sensitive. The C4 P. maximum and P. miliaceum leaf slices fed
      glycolate or glycine evolved CO2 in the dark but not in the light. In C4 species,
      dark CO2 evolution was abolished by the addition of phosphoenolpyruvate (PEP)(4).
      The addition of maleate, a PEP carboxylase inhibitor, resulted in
      photorespiratory CO2 efflux by C4 leaf slices in the light also. However, PEP and
      maleate had no effect on either glycolate-dependent O2 uptake by the C4 leaf
      slices or on glycolate and glycine metabolism in C3 leaf slices. The rate of
      photorespiratory CO2 evolution in the C3 Panicum species was 3 times higher than
      that observed with the C4 species. The ratio of glycolate-dependent CO2 evolution
      to O2 uptake in both groups was 1:2. Isolated C4 mesophyll protoplasts or their
      mitochondria did not metabolize glycolate or glycine. However, both C3 mesophyll
      protoplasts and C4 bundle sheath strands readily metabolized glycolate and
      glycine in a light-independent, O2-sensitive manner, and the addition of PEP or
      maleate had no effect. C4 bundle sheath- and C3-mitochondria were capable of
      oxidizing glycine. This oxidation was linked to the mitochondrial electron
      transport chain, was coupled to three phosphorylation sites and was sensitive to
      electron transport inhibitors. C4 bundle sheath- and C3-mitochondrial glycine
      decarboxylation was stimulated by oxaloacetate and NAD had no effect. In marked
      contrast, mitochondria isolated from C4 mesophyll cells were incapable of
      oxidizing or decarboxylating added glycine. The results suggest that in leaves of
      C4 plants bundle sheath cells are the primary site of O2-sensitive
      photorespiratory CO2 evolution and the PEP carboxylase present in the mesophyll
      cells has the Potential for efficiently refixing CO2 before it escapes out of the
      leaf. The relative role of the PEP carboxylase mediated CO2 pump and
      reassimilation of photorespiratory CO2 are discussed in relation to the apparent
      lack of photorespiration in leaves of C4 species. 

PMID- 24317561
TI  - Mitochondrial development and activity of binucleate and trinucleate pollen
      during germination in vitro.
AB  - Bi-and trinucleate pollen generally differ in the extent of their mitochondrial
      development at anther dehiscence and in the rate of their attainment of maximum
      phosphorylative capacity during germination in vitro, as judged from experiments
      with representatives of both groups.The typically trinucleate pollen of Aster
      tripolium L. immediately respired at a high rate, maintaining a high energy
      charge. Mitochondria attained maximum electron-transducing capacity within 2 min
      of incubation, while tube growth started within 3 min. In contrast, the
      binucleate pollen of Typha latifolia L. only gradually reached a relatively low
      rate of respiration, concomitant with a temporary decrease in energy charge, upon
      immersion in the germination medium. Development of the mitochondrial,
      electrontransducing system occurred in about 75 min, after which the first pollen
      tubes emerged. Starting from a poor differentiation, mitochondria became
      increasingly normal in appearance as germination proceeded.The binucleate pollen
      of Nicotiana alata Link et Otto and Tradescantia paludosa Anders. et Woods.
      showed intermediate characteristics: Nicotiana resembled Typha but mitochondria
      developed at a higher rate; Tradescantia germinated more rapidly and resembled
      the trinucleate pollen of Aster.Inhibitors of mitochondrial or cytoplasmic
      protein synthesis failed to affect the development of the mitochondrial,
      respiratory capacities during pollen germination. It is concluded that the
      duration of the lag period is determined by the level and rate of mitochondrial
      development and not by the division of the generative cell. 

PMID- 24317562
TI  - Liposome-Mediated transfer of bacterial RNA into carrot protoplasts.
AB  - The uptake of liposome-encapsulated E. coli [(3)H]RNA by carrot (Daucus carota
      L.) protoplasts was examined. [(3)H]RNA extracted from protoplasts that had been
      incubated with [(3)H]RNA-containing, large, unilamellar lipid vesicles
      (liposomes) obtained by ether infusion, and examined by sucrose gradient
      centrifugation and formamide-polyacrylamide gel electrophoresis, appeared
      substantially degraded, with a total elimination of 23S RNA and a partial loss of
      16S RNA. In contrast, no breakdown of the [(3)H]RNA was apparent in the liposomes
      after sequestration, even in the presence of externally added ribonuclease, or in
      the unfused liposomes remaining after incubation of protoplasts with liposomes.
      Thus, the degradation of the [(3)H]RNA extracted from the protoplasts must have
      occurred within the protoplasts and represents evidence for liposome-mediated RNA
      uptake. Naked RNA added to the protoplast culture was found to be totally
      degraded after incubation with the protoplasts. The uptake of liposome
      sequestered RNA by protoplasts was demonstrated to be a function both of the
      lipid composition of the liposomal membrane and of the temperature of incubation
      of the liposomeprotoplast mixture. Furthermore, the mode of this uptake (fusion
      versus endocytosis) could be manipulated by adjusting the cholesterol content of
      the liposomal membrane. The implications of the ability to insert RNA into
      protoplasts without degradation by extracellular nucleases are discussed. 

PMID- 24317563
TI  - Light stimulation of proline synthesis in water-stressed barley leaves.
AB  - The effect of light on [(14)C]glutamate conversion to free proline during water
      stress was studied in attached barley (Hordeum vulgare L.) leaves which had been
      trimmed to 10 cm in length. Plants at the three-leaf stage were stressed by
      flooding the rooting medium with polyethylene glycol 6000 (osmotic potential-19
      bars) for up to 3 d. During this time the free proline content of 10-cm second
      leaves rose from about 0.02 to 2 MUmol/leaf while free glutamate content remained
      steady at about 0.6 MUmol/leaf. In stressed leaves, the amount of
      [(14)C]glutamate converted to proline in a 3-h period of light or darkness was
      taken to reflect the in-vivo rate of proline biosynthesis because the following
      conditions were met: (a) free-glutamate levels were not significantly different
      in light and darkness; (b) both tracer [(14)C]-glutamate and [(14)C]proline were
      rapidly absorbed; (c) rates of [(14)C]proline oxidation and incorporation into
      protein were very slow. As leaf water potential fell, more [(14)C]glutamate was
      converted to proline in both light and darkness, but at any given water potential
      in the range-12 to-20 bars, illuminated leaves converted twice as much
      [(14)C]glutamate to proline. 

PMID- 24317564
TI  - Observations on the photohydrogen producing activity during the synchronous cell
      cycle of Scenedesmus obliquus.
AB  - In anaerobically adapted samples of synchronized cultures of the unicellular
      green alga Scenedesmus obliquus it was observed that both the rate and the
      maximum volume of hydrogen produced in the light changed in a parallel fashion
      over the life cycle. These two parameters of cells of the 16th h were 3 times
      greater than the comparable values for cells of the 8th h. Although both
      photosystems are involved in photohydrogen production the patterns seen over a
      complete life cycle (24 h) for hydrogen metabolism was inverse to that noted for
      changes in the photosynthetic capacity. The provision of either glucose, ethanol
      or acetate to 8th and 16th h cultures enhanced photohydrogen production of the
      8th to the same level as the 16th h. From these findings, and also from the
      observation that the starch content is low at the 8th but 4 fold at the 16th h,
      it is apparent that in autotrophic cultures an endogenous organic compound, and
      not water, serves as the electron donor for photohydrogen production. Since free
      glucose was not detected the natural substrate is most likely starch. From
      experiments with monochromatic light and observations on the inhibitory action of
      DCMU and DBMIB on photohydrogen production we conclude that the major portion of
      the machinery for photohydrogen production in Scenedesmus requires both PS I and
      PS II participation and the input of electrons from the natural substrate
      proceeds through PS II.The alternate possibility that glucose, acetate and
      ethanol also act as inhibitors of reactions, most probably photophosphorylation,
      which compete with photohydrogen production was suggested by some experiments.
      The subsequent modulation of hydrogenase activity was discussed as a possible
      reason for the enhancement of photohydrogen production. 

PMID- 24317565
TI  - Chill-induced morphological alterations in Anacystis Nidulans as a function of
      growth temperature.
AB  - Cells of Anacystis nidulans grown at 25 or 30 degrees C were examined both by
      thin-section and freeze-fracture electron microscopy. Cells grown at either
      temperature appeared similar when fixed at the growth temperature prior to
      observation. When cells were chilled to near 0 degrees C for 30 min prior to
      fixation, those previously grown at 25 degrees  appeared unchanged as judged by
      thin sectioning while those grown at 39 degrees  showed considerable
      morphological alteration. Freeze fracture showed particle aggregation (more
      pronounced in 39 degrees -grown cells) indicating lipid-phase separation in cells
      chilled prior to fixation. The phase separation was totally reversed by rewarming
      the chilled, 25 degrees -grown cells to their growth temperature but was only
      partially reversed by rewarming chilled, 39 degrees -grown cells. These results
      correlate with other effects of chilling seen in Anacystis cells grown at
      different temperatures. 

PMID- 24317566
TI  - Intracellular localization of phosphorylases in spinach and pea leaves.
AB  - Starch phosphorylase activity in extracts of spinach or pea leaves and of
      isolated chloroplasts was determined and separated by electrophoresis in
      polyacrylamide gels. In spinach leaf extracts, a specific activity of 16 nmol
      glucose 1-phosphate formed per min per mg protein was found, whereas a lower
      value (6 nmol per min per mg protein) was observed in preparations of isolated
      chloroplasts which were about 75% intact. In the spinach leaf extracts two forms
      of phosphorylase were found; chloroplast preparations almost exclusively
      contained one of these. In pea leaf extracts the specific activity was 10 nmol
      glucose 1-phosphate formed per min per mg protein. Three forms of phosphorylase
      contributed to this activity. Preparations of isolated chloroplasts with an
      intactness of about 85% exhibited a lower specific activity (5nmol per min per mg
      protein) and contained two of these three phosphorylase forms. 

PMID- 24317567
TI  - A model for proton and potassium co-transport during the uptake of glutamine and
      sucrose by tomato internode disks.
AB  - Internode disks of tomato (Lycopersicon esculentum cv. Moneymaker) were shaken in
      glutamine and sucrose solutions. At low external pH (<+/-5.5), the uptake of
      these substances was accompanied with K(+) efflux, at high pH (>+/-5.5) with K(+)
      influx. Low concentrations of external K(+) (2 mmol l(-1)) stimulated the uptake
      of glutamine, which was strongly inhibited by the supply of high K(+)
      concentrations (20 mmol l(-1)). The effect of K(+) was particularly pronounced at
      high pH-values. Addition of CCCP in light reduced the uptake of glutamine to the
      same level as in the dark, and stopped the K(+) fluxes which coincided with the
      uptake. A model is presented wherein the movements of K(+) across the membrane
      are related to co-transport, depending on the membrane potential and the Nernst
      potential of K(+). 

PMID- 24317568
TI  - Subunit composition of wheat glutenin proteins, isolated by gel filtration in a
      dissociating medium.
AB  - Proteins were extracted from wheat meal or flour in 0.1 M acetic acid, 3 M urea
      and 0.01 M CTAB and fractionated in columns of cross-linked Sepharose in the same
      solvent. An heterogeneous fraction of high molecular weight eluted from the
      column which, when reduced and subjected to SDS-polyacrylamide-gel
      electrophoresis, separated into 12 components. Their molecular weights ranged
      from about 31,500 to 136,000. The unreduced protein was insoluble in salt
      solutions and aqueous ethanol but soluble in 0.1 M acetic acid and was therefore
      defined as glutenin. Glutenins of different molecular weight were made up from
      the same subunits but in different proportions. The ethanol-soluble proteins
      (gliadins) of the flour were fractionated in Sephadex G-100. The protein
      component that was excluded from the Sephadex gel, often described as high
      molecular-weight gliadin, was shown to contain 8 distinguishable subunits and
      they had identical mobilities to 8 of the 12 subunits of glutenin. 

PMID- 24317569
TI  - Ultrastructural and autoradiographic study of the intranuclear inclusions of
      Pinguicula lusitanica L.
AB  - Intranuclear inclusions are found in Pinguicula lusiaanica. Observations with an
      electron microscope equipped with a goniometric stage demonstrate that they are
      formed with numerous similarly oriented lamellae. Enzyme digestions of ultrathin
      sections show that the inclusions are composed of protein. An autoradiographic
      study, after incubation of pieces of leaves or roots in a physiological medium
      containing tritiated arginine, shows that the inclusions grow in tissue incubated
      in such an artificial mineral medium. 

PMID- 24317570
TI  - A survey for isoenzymes of glucosephosphate isomerase, phosphoglucomutase,
      glucose-6-phosphate dehydrogenase and 6-Phosphogluconate dehydrogenase in C3-, C
      4-and crassulacean-acid-metabolism plants, and green algae.
AB  - Two isoenzymes each of glucosephosphate isomerase (EC 5.3.1.9),
      phosphoglucomutase (EC 2.7.5.1), glucose-6-phosphate dehydrogenase (EC 1.1.1.49)
      and 6-phosphogluconate dehydrogenase (EC 1.1.1.43) were separated by (NH4)2SO4
      gradient solubilization and DEAE-cellulose ion-exchange chromatography from green
      leaves of the C3-plants spinach (Spinacia oleracea L.), tobacco (Nicotiana
      tabacum L.) and wheat (Triticum aestivum L.), of the Crassulacean-acid-metabolism
      plants Crassula lycopodioides Lam., Bryophyllum calycinum Salisb. and Sedum
      rubrotinctum R.T. Clausen, and from the green algae Chlorella vulgaris and
      Chlamydomonas reinhardii. After isolation of cell organelles from spinach leaves
      by isopyenic centrifugation in sucrose gradients one of two isoenzymes of each of
      the four enzymes was found to be associated with whole chloroplasts while the
      other was restricted to the soluble cell fraction, implying the same
      intracellular distribution of these isoenzymes also in the other species.Among C4
      plants, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase
      were found in only one form in corn (Zea mays L.), sugar cane (Saccharum
      officinarum L.) and Coix lacrymajobi L., but as two isoenzymes in Atriplex
      spongiosa L. and Portulaca oleracea L. In corn, the two dehydrogenases were
      mainly associated with isolated mesophyll protoplasts while in Atriplex spongiosa
      they were of similar specific activity in both mesophyll protoplasts and bundle
      sheath strands. In all five C4-plants three isoenzymes of glucosephosphate
      isomerase and phosphoglucomutase were found. In corn two were localized in the
      bundle-sheath strands and the third one in the mesophyll protoplasts. The amount
      of activity of the enzymes was similar in each of the two cell fractions.
      Apparently, C4 plants have isoenzymes not only in two cell compartments, but also
      in physiologically closely linked cell types such as mesophyll and bundle-sheath
      cells. 

PMID- 24317571
TI  - Inhibition of the circadian rhythm of CO2 metabolism in Bryophyllum leaves by
      cycloheximide and dinitrophenol.
AB  - The circadian rhythm of CO2 output in darkened leaves of Bryophyllum fedtschenkoi
      R. Hamet and Perrier can be inhibited by cycloheximide (?10(-6) mol) and 2,4
      dinitrophenol (?10(-5) mol) applied via the transpiration stream. After having
      been suppressed by 10(-6) M cycloheximide, the rhythm can be reinitiated with a
      12-h exposure to light. Experiments using (14)CO2 show that cycloheximide
      abolishes the rhythm by inhibiting the dark fixation of CO2. Cycloheximide
      inhibits malate accumulation and acidification of the leaves, but does not affect
      the amount of the CO2-fixing enzyme phosphoenol-pyruvate carboxylase (PEP-C, EC
      4.1.1.31) which can be extracted from the leaves during the 45 h of the
      experiment. Cycloheximide has no direct effect on the activity of the enzyme as
      measured in the assay. PEP-C from desalted leaf extracts was inhibited by L
      malate (Ki=0.4 mmol). The most likely explanation for the inhibitory effect of
      cycloheximide and dinitrophenol is that they cause changes in tonoplast
      properties which result in a redistribution of malate from the vacuole to the
      cytoplasm. An increase in malate concentration in the cytoplasm will lead to
      inhibition of PEP-carboxylase, and hence the suppression of the rhythm of CO2
      output. 

PMID- 24317572
TI  - The genetic basis of egg lay response to conditioned medium in the flour beetle,
      Tribolium castaneum : I. Two-way selection.
AB  - The rate of egg laying in Tribolium castaneum is affected by the quality of the
      environment and can thus serve not only as a component of fitness of the
      individual, but also as an adaptation to the long-term survival of the
      population. In an attempt to determine whether it is an independent genetic
      character, selection for high and low rates of response was carried jut in
      beetles from three wild populations. When tests were done on virgin females, and
      responsiveness, corrected for scale effects, was used as the criterion for
      selection, separation between the lines was achieved in one generation. It is
      suggested that in natural populations of Tribolium, the responsiveness of the
      rate of egg laying to the quality of the environment is controlled by a small
      number of genes. 

PMID- 24317573
TI  - The influence of aberrant values on the statistics related to a selection
      program.
AB  - Examples are presented to illustrate some of the effects aberrant values, in
      particular, measurement errors, may have on estimates of the genetic parameters
      related to selection studies. It is shown that aberrant values may cause observed
      response to selection pressure to differ considerably from predicted response.
      Possible dangers of indiscriminate screening are also discussed. 

PMID- 24317574
TI  - Interspecific hybridization of phaseolus vulgaris with P. lunatus and P.
      acutifolius.
AB  - The influence of genotypic combinations on the growth of hybrid embryos between
      Phaseolus vulgaris and P. lunatus, and between P. vulgaris and P. acutifolius was
      examined. All embryos obtained from P. vulgaris * P. lunatus crosses developed
      only to a stage which appears to be comparable to the pre-heart-shape stage of
      selfed embryos. Reciprocal crosses were attempted, but pods abscised at a very
      early stage. Embryos derived from P. vulgaris * P. acutifolius and reciprocal
      crosses attained the cotyledon stage although no mature seeds were formed. A
      distinct characteristic of these embryos was the uneven development of the two
      cotyledons. The rate of growth and final size of these hybrid embryos seemed to
      be influenced by the genotypes of both parents.Immature embryos were cultured on
      defined medium and the effects of glutamine and gibberellin (GA3) were examined.
      Glutamine was effective in increasing the survival rate; gibberellin had no
      apparent effect. Plants derived from cultured embryos of P. vulgaris * P.
      lunatus, P. vulgaris * P. acutifolius and P. acutifolius * P. vulgaris were
      obtained. 

PMID- 24317575
TI  - Elucidation of the evolution and taxonomy of cultivated potatoes with
      electrophoresis : I. Groups tuberosum, andigena, phureja and stenotomum.
AB  - A recently developed polyacrylamide gel electrophoresis technique for tuber
      proteins is used to help elucidate the evolution and taxonomy of some cultivated
      potatoes. The results substantiate the theory that Group Tuberosum evolved from
      Group Andigena, that Group Andigena evolved from a cultivated diploid * wild
      diploid hybrid, and that Group Phureja evolved from Group Stenotomum.
      Furthermore, the results suggest these groups are closely enough related to merit
      classification within a single species. 

PMID- 24317576
TI  - Change in the amino-acid content during male gametophyte formation of Datura
      metel in Situ.
AB  - Determination of the free and bound aminoacids during microsporogenesis of Datura
      metel showed that the principal amino-acids were proline, glutamic acid, aspartic
      acid, threonine-serine and alanine. Of these, only proline showed a consistent
      increment during pollen development. In contrast, aspartic acid and lysine
      decreased in the later stages of microsporogenesis. The amounts of other amino
      acids did not show any consistent pattern. Four amino-acids, namely proline,
      glutamic acid and threonine-serine constituted nearly 85% of the free amino-acid
      pool in the developed anther (stage IV). Proline accumulation, relative to the
      total free amino-acid pool in mature anthers, was correlated with the water
      content. The results were discussed in view of possible relationships between
      metabolic activity and free and bound amino-acid concentrations. 

PMID- 24317577
TI  - A replicated single generation test of a restricted selections index in poultry.
AB  - Predicted and realized responses in a single generation of mass selection for an
      index and for its component traits were compared. The index included the log
      transformed traits determining egg mass in chickens to 40 weeks of age (days
      tested from sexual maturity, egg weight, rate of lay). The index was restricted
      to allow no increase in log days tested. Other traits measured were egg mass, age
      at first egg, egg weight, rate of lay, number of eggs and body weight. When
      averaged over replicates, realized and predicted responses were in close
      agreement for index values and for the component traits. Significant
      corresponding correlated responses were obtained for egg mass and weight. The
      restricted trait, log days tested, and the correlated trait age at first egg did
      not change. Egg mass was increased solely through change in egg weight. 

PMID- 24317578
TI  - Time of cross- and self-pollination affects the amount of self-seed set by
      partially self-incompatible plants of Brassica oleracea.
AB  - The relative ability of cross- and self-pollen to achieve fertilisation in
      Brassica was studied by making double pollinations using cross-pollen carrying a
      dominant seedling marker gene. With simultaneous self- and crosspollination 12
      40% self-seed was set, but when cross-pollen was applied to the stigma four hours
      before self-pollen, only 2-4% self-seed was obtained. In two plants to which
      cross-pollen was applied at various time intervals after self-pollen there was a
      tendency for the percentage of self-seed to increase as the time interval
      increased. In a third plant this trend was not apparent, probably because of a
      greater degree of self-incompatibility. The competitive advantage of the first
      pollen to arrive on the stigma is discussed in relation to the strength of the
      self-incompatibility and the sib problem in F1 hybrid brassicas. 

PMID- 24317579
TI  - Correction.

PMID- 24317581
TI  - Constructing (super)alkali-boron-heterofullerene dyads: an effective approach to
      achieve large first hyperpolarizabilities and high stabilities in M3O-BC59 (M =
      Li, Na and K) and K@n-BC59 (n = 5 and 6).
AB  - Using DFT methods, the electronic properties and the first hyperpolarizabilities
      of boron-heterofullerene-(super)alkali dyads: M3O-BC59 (M = Li, Na and K) and K@n
      BC59 (n = 5 and 6) were systematically investigated. It is found that both M3O
      and K can effectively bind to BC59 with high binding energies (2.50-2.69 eV for K
      and 4.24-5.14 eV for M3O). The interaction between K and BC59 in K@n-BC59 is
      identified as primarily ionic in nature, whereas that between the superalkali M3O
      unit and BC59 becomes much stronger owing to the formation of a strong chemical
      bond (B-O bond). Moreover, compared with the sole parent cluster BC59 (619 au),
      both K@n-BC59 (n = 5 and 6) and M3O-BC59 (M = Li, Na and K), possess large first
      hyperpolarizabilities (beta0), which are 3352, 2621 and 4921, 5440 and 7800 au,
      respectively, where the superalkali doped dyads (M3O-BC59) are much superior to
      the simple alkali exo-hedral species (K@n-BC59), and heavier superalkali can be
      more powerful in enhancing the beta0 values of M3O-BC59. Clearly, these
      superalkali doped dyads M3O-BC59, formal donor-acceptor (DA) chromophores,
      exhibit not only excellent stability but also large first hyperpolarizability;
      therefore, they are expected to be potential candidates for excellent second
      order NLO materials.

PMID- 24317580
TI  - Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and
      induce synthetic lethality in BRCA mutant cells.
AB  - Poly(ADP-ribose) polymerase (PARP) inhibitors have been proven to represent
      superior clinical agents targeting DNA repair mechanisms in cancer therapy. We
      investigated PARP inhibitory effects of the natural and synthetic flavonoids
      (quercetin, rutin, monoglucosyl rutin and maltooligosyl rutin) and tested the
      synthetic lethality in BRCA2 mutated cells. In vitro ELISA assay suggested that
      the flavonoids have inhibitory effects on PARP activity, but glucosyl
      modifications reduced the inhibitory effect. Cytotoxicity tests of Chinese
      hamster cells defective in BRCA2 gene (V-C8) and its parental V79 cells showed
      BRCA2-dependent synthetic lethality when treated with the flavonoids. BRCA2
      mutated cells were three times more sensitive to the flavonoids than the wild
      type and gene complemented cells. Reduced toxicity was observed in a glucosyl
      modification-dependent manner. The present study provides support for the
      clinical use of new treatment drugs, and is the beginning of the potential
      application of flavonoids in cancer prevention and the periodic consumption of
      appropriate flavonoids to reduce cancer risk in individuals carrying a mutant
      allele of the BRCA2 gene.

PMID- 24317582
TI  - Marking urine and preputial gland secretion of male bank voles (Clethrionomys
      glareolus L.) chemical analyses and behavioral tests.
AB  - Urine and preputial gland secretion of male bank voles were analyzed by gas
      chromatography (GC) and mass spectrometry (MS) (selected ion monitoring, SIM). GC
      MS analyses showed the presence of hexadecyl acetate in preputial gland secretion
      and in marking urine but not in metabolic urine. Female bank voles responded more
      strongly to marking urine of males than to metabolic urine, and they responded
      more to preputial gland secretion (pure or added to urine) than to metabolic
      urine. Dominant males spent more time and marked more frequently in response to
      hexadecyl acetate-enriched urine than to urine alone. The opposite reaction was
      shown by subordinate males. The results suggest that the acetate functions in the
      bank voles' dominance interactions. 

PMID- 24317583
TI  - Identification of new sex pheromone components inTrichoplusia ni, predicted from
      biosynthetic precursors.
AB  - In addition to the previously identified components (Z)-7-dodecenyl acetate and
      dodecyl acetate, sex pheromone glands ofTrichoplusia ni release (Z)-5-dodecenyl
      acetate, 11-dodecenyl acetate, (Z)-7-tetradecenyl acetate, and (Z)-9-tetradecenyl
      acetate. Bioassays in a flight tunnel showed that a synthetic blend of these six
      compounds elicited complete flights to the source from 95% of the males tested
      and elicited hairpenciling responses at the end of the flights from 88% of the
      males tested. This blend was not significantly different from intact pheromone
      glands, which elicited complete flights to the source from 98% of the males
      tested and hairpenciling responses from 91% of the males tested. In contrast, the
      previously identified two-component blend elicited significantly fewer complete
      flights to the source (33%) and did not elicit hairpenciling responses from any
      of the males tested. The search for additional sex pheromone components was
      prompted by our previous identification of unusual fatty acyl moieties in the
      gland that seemed to be possible biosynthetic intermediates. 

PMID- 24317584
TI  - Response of Colorado potato beetles,Leptinotarsa decemlineata (Say), to volatile
      components of tansy,Tanacetum vulgare.
AB  - The responses of Colorado potato beetle,Leptinotarsa decemlineata (Say), to
      volatile components of tansy,Tanacetum vulgare L., were investigated in order to
      establish a chemical basis for observed reduction in beetle populations when
      potatoes,Solanum tuberosum L., were interplanted with tansy. Colorado potato
      beetles exhibited avoidance behavior to tansy oil, volatiles from intact tansy
      plants, a "hydrocarbon fraction" of tansy oil, obtained by fractionation on
      alumina, and five of the 13 known components of tansy oil that were tested. One
      constituent of tansy oil, alpha-pinene, attracted beetles. 

PMID- 24317585
TI  - Alkanes from surface lipids of sunflower stem weevil,Cylindrocopturus adspersus
      (LeConte).
AB  - The stem weevil,Cylindrocopturus adspersus (LeConte) (Coleoptera: Curculionidae)
      yields 3% of its body weight as extractable lipids (40 MUg/ weevil). The alkane
      fraction was composed ofn-alkanes (38%) and branched alkanes (62%). The compounds
      were characterized by gas chromatography-mass spectrometry (GC-MS). The
      chromatogram contained several single-component peaks (9 of 25). Only seven
      dimethylalkanes were isolated (17.8%): 9,19- and 9,21-dimethylheptacosane; 9,19-
      and 9,21-dimethylnonacosane; 9,21- and 11,21-dimethylhentriacontane; and 11,21
      dimethyltritriacontane. Important methylalkanes were: 2-methyltetra- and
      hexacosanes and 10-methylhexa- and octacosanes. Late-eluting gas chromatography
      peaks were composed of simple alkane mixtures or a single component. 

PMID- 24317586
TI  - Interconversion of verbenols and verbenone by identified yeasts isolated from the
      spruce bark beetleIps typographus.
AB  - Six yeast strains have been isolated and identified from the spruce bark
      beetle,Ips typographus. We have studied the ability of the yeasts to
      interconvertcis-verbenol,trans-verbenol, and verbenone. (1S)-cis-Verbenol is an
      active component in the aggregation pheromone ofIps typographus. The
      isolatedCandida molischiana/ Hansenula capsulata strain can convert both (1R)-
      and (1S)-cis-verbenol to verbenone. TheCandida nitratophila strain converts (1R)
      cis-verbenol totrans-verbenol and (1S)-cis-verbenol to verbenone. Some of the
      yeast strains produce 3-methylbutanol, 2-methylpropanol, and 2-phenylethanol
      after growth in Sabouraud medium. 

PMID- 24317587
TI  - Diterpene composition of defense secretion of four west AfricanTrinervitermes
      soldiers.
AB  - The diterpene composition of the defensive secretions of minor and major soldiers
      is described for four sympatricTrinervitermes from the Ivory Coast. The degree of
      intra- and interspecific similarity between the secretions is assessed and
      related to available information on soldier behavior. A significant chemical
      dimorphism is observed between minor and major soldiers ofT. geminatus andT.
      togoensis. Both species build extensive foraging trails in the open air. During
      these excursions, the workers are protected by numerous minor soldiers, but only
      a few major ones. Internest comparison inT. geminatus suggests that the
      differences between minor and major soldiers is as large within a nest as between
      different nests. By, contrast, inT. trinervius andT. oeconomus both types of
      soldiers produce very similar secretions. The foraging habits of those species
      are far more cryptic. The first species builds earthen tunnels, and the second
      one forages in close proximity to its nest under cover of vegetation. 

PMID- 24317588
TI  - Sex attractant for currant clearwing mothSynanthedon tipuliformis (Clerck)
      (Lepidoptera: Sesiidae).
AB  - The currant clearwing moth,Synanthedon tipuliformis (Clerck) (Lepidoptera:
      Sesiidae), is a pest in many parts of the world. In field tests it was found that
      (E,Z)-2,13-octadecadien-1-ol acetate attracts males of this species. The
      synthesis of this compound and of its geometrical isomer (Z,Z)-2,13-octadecadien
      1-ol acetate is described. 

PMID- 24317589
TI  - Potential uses of kairomones for behavioral manipulation ofCotesia marginiventris
      (Cresson).
AB  - The effects of kairomone pattern and preconditioning on parasitization rates of
      fall armyworm larvae,Spodoptera frugiperda (J.E. Smith) byCotesia
      (=Apanteles)marginiventris (Cresson) were investigated in the laboratory and
      greenhouse using a hexane extract of frass and actual fall armyworm frass.
      Parasitization rates increased 55 and 26% in Petri dishes and on corn seedlings,
      respectively, when the entire experimental area was sprayed with the frass
      extract. Applying the extract in spots resulted in a 20-30% reduction in
      parasitization compared to treating the entire area. However, spot application
      produced significantly better parasitization rates compared to the control
      treatment. Exposing the parasitoids to actual fall armyworm frass resulted in ca.
      50% greater retention in the release area and an increase of ca. 60-75% in the
      number of parasitoids searching.C. marginiventris parasitized factitious hosts
      topically treated with an extract of fall armyworm frass. 

PMID- 24317590
TI  - Sex pheromones inCulicoides nubeculosus (diptera, ceratopogonidae): Possible
      sites of production and emission.
AB  - This study was performed on virgin females ofCulicoides nubeculosus to determine
      sites of production and emission of sex pheromone. The ventral abdominal surface
      is the site of emission of the pheromone. Morphologically there is evidence of
      the presence of abdominal atrichial areas. The abdominal areas, eight per segment
      (four ventral and four dorsal), are covered by a cuticle devoid of micro- and
      macrotrichiae. The dorsal and ventral areas differ considerably in their
      structure. The dorsal atrichial areas have an unperforated cuticle covering a
      normal epidermis, whereas the ventral atrichial areas have a cuticle perforated
      by numerous tubular structures, with a loosely organized procuticle and no
      underlying epidermal cells. A pair of voluminous cells with the classical
      ultrastructural characteristics of enocytes is invariably located in the vicinity
      of the ventral atrichial areas. These cells undergo ultrastructural modifications
      tending towards involution according to the age of the insects, being correlated
      with the decrease in pheromone emission by older females. The hypothesis is put
      forward that enocytes are involved in pheromone production. 

PMID- 24317591
TI  - Host acceptance and discrimination byComperia merceti (Compere) (Hymenoptera:
      Encyrtidae) and evidence for an optimal density range for resource utilization.
AB  - The cement used by females ofSupella longipala (F.) (Orthoptera?Blattellidae) to
      bind their oothecae to substrates acts as a kairomone for host acceptance by the
      parasitoidComperia merceti. C. merceti discriminates parasitized from
      unparasitized oothecae and oviposts at reduced levels in the former. Low survival
      rates for parasitoids reared from oothecae receiving fewer than four ovipositions
      suggests that an "optimal density range" for resource utilization byC. merceti
      exists. 

PMID- 24317592
TI  - Responses of wild muskrats (Ondatra zibethicus L.) to scented traps.
AB  - Free-ranging muskrats were trapped in scented and blank traps in New York State
      at local ponds during all seasons and at a wildlife refuge in spring and early
      summer. In a total of 4839 trap-nights, 65 muskrats were caught. Trapping success
      was 1.34%. The overall responses to differently scented traps differed
      significantly. Adults preferentially entered blank and food-baited traps, whereas
      young showed no preference to blank, musk, or control odor. It appears that
      adults actively avoid musk, especially during the months May through July. 

PMID- 24317593
TI  - The transport properties of oxygen vacancy-related polaron-like bound state in
      HfOx.
AB  - The oxygen vacancy-related polaron-like bound state migration in HfOx accounting
      for the observed transport properties in the high resistance state of resistive
      switching is investigated by the density functional theory with hybrid
      functional. The barrier of hopping among the threefold oxygen vacancies is
      strongly dependent on the direction of motion. Especially, the lowest barrier
      along the <001> direction is 90 meV, in agreement with the experimental value
      measured from 135 K to room temperature. This hopping mainly invokes the z
      directional motion of hafnium and threefold oxygen atoms in the vicinity of the
      oxygen vacancy resulted from the synergized combination of coupled phonon modes.
      In the presence of surface, the lowest barrier of hopping between the surface
      oxygen vacancies is 360 meV along the <101> direction, where the significant
      surface perpendicular motion of hafnium and twofold oxygen atoms surrounding the
      oxygen vacancy is identified to facilitate this type of polaron-like bound state
      migration. Thus, the migration on the surfaces could be more important at the
      high temperature.

PMID- 24317594
TI  - Genetic control of resistance to crown rust (Puccinia coronato Corda) in Lolium
      perenne L. and its implications in breeding.
AB  - A genetic analysis of resistance to crown rust in a series of natural populations
      of Lolium perenne by means of the diallel cross has revealed that heritability is
      high (58%) and that the genes concerned show complete but ambi-directional
      dominance for resistance. An environmental correlation was established between
      the degree of infection and productivity but no genetic correlation was present.
      The implications of this mode of control for resistance breeding procedures are
      briefly considered. 

PMID- 24317595
TI  - Effect of giving insulin and adrenalin alternately on changes in the level of
      blood glucose in chickens of different breeds.
AB  - Differences in reaction to exogenous insulin and adrenalin were studied among
      chickens of 'Leghorn', 'White Rock' and 'Rhode Island Red' breeds, using level of
      blood glucose as indicator of the reaction to hormones. It was found that: 1.)
      The physiological quantity of glucose in blood in chickens of the three breeds
      ranged from 157 to 194 mg %. 2.) The reaction of chickens to insulin and
      adrenalin given alternately, measured by changes of blood glucose, differed
      according to the breed. The smallest reaction to hormones was in 'Leghorn', the
      biggest in 'White Rock'. 3.) The chickens of 'Leghorn' and 'Rhode Island Red'
      breeds, as well as 'Leghorn' and 'White Rock' breeds, differed significantly in
      maximal glucose level after adrenalin, 4.) The correlation between the normal
      quantity of blood glucose and the body weight of birds appeared highly
      significant in cockerels of all three races combined. 

PMID- 24317596
TI  - The activity of lactate and malate dehydrogenases in the blood serum of chickens
      of various breeds and crossbreds.
AB  - Studies on the activity of lactate and malate dehydrogenases in the blood serum
      of 'Leghorn', 'Greenleg' and 'White Rock' chickens and their crossbreds have
      shown that: 1. The highest activity of both enzymes occurs in 'Greenleg' chicken,
      and the lowest in the 'Leghorn' birds. 2. The mean activity of both enzymes in
      crossbreds was considerably higher than that obtained for the control, purebred
      birds. 3. The mean activity of both enzymes was higher for crossbreds than for
      the whole population. 

PMID- 24317597
TI  - Inheritance of resistance to neonatal E. coli diarrhoea in the pig: examination
      of the genetic system.
AB  - Evidence is presented that a dominant allele, S, is expressed as a receptor for
      K88 on the brushborder surface of the pig intestinal cell. The homozygous
      recessive (ss) lacks this receptor. The receptor enables K88 - positive coliforms
      to adhere to the gut of the piglet which they must do if they are to cause
      neonatal diarrhoea. The homozygous recessive is thus a disease resistant animal.A
      possible reason for the persistence of the dominant (susceptible) gene is given. 

PMID- 24317598
TI  - Genetic variability and improvement of seed proteins in wheat.
AB  - Albumins, globulins, gliadins and glutenins presumably comprising 100 percent of
      the wheat seed proteins were sequentially extracted and electrophoresed on SDS
      polyacrylamide gels. The SDS-electrophoretic patterns within each of the four
      fractions from T. boeotiaum, T. urartu, T. turgidum, T. timopheevii, T. aestivum,
      Ae. speltoides and Ae. squawosa were similar. They differed from one species to
      another only in a few minor components or density of certain components.
      Similarity in MW's of components, as indicated by the SDS-electrophoretic
      patterns, suggests that the wheats and Aegilops exhibit no variability for
      structural genes coding seed proteins. A minimum of 60 to 70 and a maximum of 360
      to 420 structural genes with major or minor effects control the total seed
      protein in T. aestivum. Presumably, only one or the other homoeoallele was
      expressed in the polyploids. Different components of albumins and globulins
      presumably had distinct MW's and amino acid composition, while the components of
      gliadins and glutenins could be classified into a few groups each containing one
      or more components with the same MW and nearly identical amino acid composition.
      The genes for components with similar MW's and amino acid composition arose
      through multiplication of a single original gene and perhaps share the same
      regulatory mechanism. Seed protein content and quality in wheat might be improved
      through the incorporation of structural genes, coding for polypeptides with
      distinct MW's, from distantly related species, rather than by manipulation of the
      structural genes within the Triticum-Aegilops group. Regulatory mutants similar
      to opaque-2 of corn could be used to alter the proportion of gliadins in relation
      to albumins and globulins, to improve amino acid composition of wheat proteins. 

PMID- 24317599
TI  - Increased induction and chromosome doubling of androgenetic haploid rye.
AB  - Further progress of studies aimed at increasing production of androgenetic Secale
      cereale plants via the culture of anthers is described. Two culture media
      initially developed for rice and wheat anther culture have been shown to have
      pronounced influence on rye. It has been possible to increase the average
      percentages of responsive anthers (i.e. those producing embryoids or calluses)
      from 0.26% to 10% with a maximum in certain experiments of over 40 %. Of nearly
      400 plants produced in 1976, 1/4 are green and can be grown further by transfer
      to potting compost; 3/4 are albino. Stable green haploid lines were present
      amongst the plants, and after vegetative propagation of the lines representative
      samples have been treated with colchicine resulting in diploid, triploid and
      tetraploid plants. The influence of the genetic background of the donor plants on
      the success rate of anther culture and on the percentage of albino formation is
      discussed. 

PMID- 24317600
TI  - Effect of starvation on the content of free amino acids in plasma of different
      breeds of hen.
AB  - 'Leghorn', 'Cornish' and 'White Rock' hens were subjected to starvation. Free
      amino acids were determined in blood samples taken after 48, 72 and 96 h of
      starvation. A progressive decrease in concentration of the majority of amino
      acids was found. Changes in amino acid concentrations during starvation were
      dependent on the breed of hen. 

PMID- 24317601
TI  - Corrections.

PMID- 24317602
TI  - Cystitis: antibiotic prescribing, consultation, attitudes and opinions.
AB  - BACKGROUND: Despite stable overall antibiotic use between 2007 and 2011 in The
      Netherlands, use of nitrofurantoin and trimethoprim increased by 32%. The
      background of this increased antibiotic use against uropathogens is unknown.
      OBJECTIVES: To determine whether increased use of urinary tract infection
      antibiotics is caused by changes in patients' consultation or physicians'
      prescribing behaviour and to investigate attitudes and opinions of women with
      respect to cystitis management and antibiotics. METHODS: Consultation and
      prescribing for International Classification of Primary Care (ICPC) codes U01
      (dysuria), U02 (frequency), U05 (other urination problems), U70 (pyelonephritis)
      and U71 (cystitis) were determined from 2007 to 2010, using routinely collected
      primary health care data. Separately, behaviour of women with respect to managing
      cystitis, consultation and opinions towards (delayed) antibiotic treatment were
      studied using questionnaires in 2012. RESULTS: Consultation for U02 and U71
      significantly increased from 93 to 114/1000 patient-years from 2007 to 2010;
      proportion of episodes in which an antibiotic was prescribed remained constant.
      Questionnaires revealed that urination problems and pain were dominant complaints
      of cystitis; pain medication, however, was not adequately used. One-third of
      women directly consult upon first symptoms, whereas the majority awaits an
      average of 4 days. Sixty-six per cent of women report to be willing to postpone
      antibiotic use. CONCLUSION: Increased use of urinary tract infection antibiotics
      may be caused by increased consultation for cystitis in primary care. Future
      research should focus on the outcomes of adequate pain medication, enhanced
      diagnostic procedures and of delaying antibiotic use in cystitis management.

PMID- 24317603
TI  - Mammalian diaphanous-related formin 1 is required for motility and invadopodia
      formation in human U87 glioblastoma cells.
AB  - Characterized by invasive growth and infiltrative dissemination, glioma is poorly
      diagnosed and prognosed at present. The mammalian diaphanous-related formin 1
      (mDRF1), which is involved in a number of actin-related biological processes, has
      been found to participate in the process of invasion and metastasis in human
      breast cancer cells and to show abnormal expression under pathological
      conditions. However, the role of mDRF1 in glioma is not clear. In this study, we
      carried out a comprehensive analysis of the effects of mDRF1 on human glioma. We
      used siRNA to knock down mDRF1 expression in highly invasive U87 malignant glioma
      (MG) cells and examined the changes in cell proliferation, apoptosis, invasion
      and migration. Atomic force microscopy was used to examine invadopodia formation.
      Immunohistochemical and immunocytochemical assays were used to analyze the
      cellular localization and the expression levels of mDRF1 in human glioma tissue
      and in the U87 MG cells. Following the transfection of U87 MG cells with siRNA
      mDRF1, their in vitro proliferation was significantly decreased, apoptosis was
      markedly increased, and invasion and metastasis were significantly inhibited. The
      results from atomic force microscopy revealed that invadopodia were formed at
      leading the edge of the U87 MG cells. However, following the silencing of mDRF1
      by siRNA, the edge of the cells became smooth and the invadopodia disappeared.
      For in vivo experiments, nude mice were transplanted with tumor cells and then
      treated with siRNA-mDRF1. The results revealed that treatment with siRNA-mDRF1
      significantly inhibited tumor growth and led to a decrease in the weight of the
      transplanted tumor. In conclusion, our data demonstrate that mDRF1 is highly
      expressed in human glioma tissue. The knockdown of mDRF1 in U87 MG cells led to a
      sharp decline in their invasive and metastatic ability, which effectively reduced
      the spread of glioma cells into the surrounding areas. To our knowledge, this is
      the first report showing that mDRF1 is a promising target for the treatment of
      malignant gliomas.

PMID- 24317605
TI  - Extended pilot badger cull ends early in Gloucestershire.

PMID- 24317606
TI  - Defra proposes new cattle controls to combat the spread of bovine TB.

PMID- 24317607
TI  - Livestock-associated MRSA found on a poultry farm in East Anglia.

PMID- 24317608
TI  - Edinburgh establishes link with Hong Kong.

PMID- 24317609
TI  - Exotic pets: is there a problem?

PMID- 24317610
TI  - A positive approach to stress.

PMID- 24317612
TI  - Evidence-based medicine: can we trust the evidence?

PMID- 24317613
TI  - Veterinary medicines: product update.

PMID- 24317614
TI  - Unusual spinal cord disorders identified in calves.

PMID- 24317615
TI  - Reducing antimicrobial resistance.

PMID- 24317616
TI  - Are Britain's cats ready for cat cafes?

PMID- 24317617
TI  - Reporting rabies risk.

PMID- 24317618
TI  - Implementing risk-based trading.

PMID- 24317619
TI  - Keeping exotic pets.

PMID- 24317620
TI  - Grammatical exactitude.

PMID- 24317631
TI  - A novel pollution index based on the bioavailability of elements: a study on
      Anzali wetland bed sediments.
AB  - In this research, we study on the distribution of several elements in bed
      sediments of Anzali wetland. Anzali, one of the most important international
      wetlands, is located on the southern coast of the Caspian Sea in Iran. This
      wetland receives discharges of domestic, agricultural, and industrial wastewater,
      which affect the distribution of elements. Our contribution in this study is
      threefold. First, we measured the total concentration of metals as well as their
      chemical partitioning and bioavailability in the sediments. Second, we calculated
      anthropogenic portions of metals in the sediment of this area. The results reveal
      anthropogenic portion of metals as Mo > Mn > Cd > As > Zn > Hg > Co > Sn > Cu > V
      > Ag > Ni > Pb > Fe > Cr > Al, respectively. We evaluated the intensity of
      pollution by using an enrichment factor, the geo-accumulation index and the
      pollution index. All these indices do not take into consideration the
      bioavailability of the elements. As our third and most important contribution, we
      introduced a new formula that takes into account the bioavailability of different
      elements. In comparison with aforementioned pollution indices, our newly
      introduced pollution index has a higher Pearson correlation with anthropogenic
      portion of metals. This high-correlation coefficient shows that our proposed
      pollution index is an effective indicator for determining the level of pollution,
      while other indices preserve their own merits. 

PMID- 24317632
TI  - Technique of implantation and bail-out maneuvers for endovascular fenestrated
      repair of juxtarenal aortic aneurysms.
AB  - Endovascular repair of complex aneurysms involving the visceral arteries has
      become a reality. Fenestrated endovascular aortic repair (FEVAR) has been used
      with increasing frequency to treat complex aortic aneurysms. The Zenith
      fenestrated stent-graft system (Cook Medical Inc, Brisbane, Australia) was
      approved for commercial use in the United States in April 2012, offering a custom
      made design with up to 3 fenestrations to treat short-neck infrarenal and
      juxtarenal abdominal aortic aneurysms. Nevertheless, FEVAR is a complex procedure
      that demands accurate planning, advanced endovascular skills, and excellent
      perioperative patient care to achieve optimal outcomes. This article summarizes
      the basic concepts of device design, case planning, techniques of implantation,
      and some of the "bail-out" maneuvers that may be required during endovascular
      repair using the Zenith fenestrated stent-graft system. 

PMID- 24317633
TI  - Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron
      thiosemicarbazone complexes: relevance to iron-chelator-induced
      methemoglobinemia.
AB  - The oxidation of oxyhemoglobin to methemoglobin has been found to be facilitated
      by low molecular weight iron(III) thiosemicarbazone complexes. This deleterious
      reaction, which produces hemoglobin protein units unable to bind dioxygen and
      occurs during the administration of iron chelators such as the well-known 3
      aminopyridine-2-pyridinecarbaldehyde thiosemicarbazone (3-AP; Triapine), has been
      observed in the reaction with Fe(III) complexes of some members of the 3-AP
      structurally-related thiosemicarbazone ligands derived from di-2-pyridyl ketone
      (HDpxxT series). We have studied the kinetics of this oxidation reaction in vitro
      using human hemoglobin and found that the reaction proceeds with two distinct
      time-resolved steps. These have been associated with sequential oxidation of the
      two different oxyheme cofactors in the alpha and beta protein chains. Unexpected
      steric and hydrogen-bonding effects on the Fe(III) complexes appear to be the
      responsible for the observed differences in the reaction rate across the series
      of HDpxxT ligand complexes used in this study. 

PMID- 24317634
TI  - A neurologist with a lifetime fascination for neurochemistry: preface for the
      special issue dedicated to Dr. Andreas Plaitakis. Preface.

PMID- 24317635
TI  - Probenecid protects against transient focal cerebral ischemic injury by
      inhibiting HMGB1 release and attenuating AQP4 expression in mice.
AB  - Stroke results in inflammation, brain edema, and neuronal death. However,
      effective neuroprotectants are not available. Recent studies have shown that high
      mobility group box-1 (HMGB1), a proinflammatory cytokine, contributes to ischemic
      brain injury. Aquaporin 4 (AQP4), a water channel protein, is considered to play
      a pivotal role in ischemia-induced brain edema. More recently, studies have shown
      that pannexin 1 channels are involved in cerebral ischemic injury and the
      cellular inflammatory response. Here, we examined whether the pannexin 1 channel
      inhibitor probenecid could reduce focal ischemic brain injury by inhibiting
      cerebral inflammation and edema. Transient focal ischemia was induced in C57BL/6J
      mice by middle cerebral artery occlusion (MCAO) for 1 h. Infarct volume,
      neurological score and cerebral water content were evaluated 48 h after MCAO.
      Immunostaining, western blot analysis and ELISA were used to assess the effects
      of probenecid on the cellular inflammatory response, HMGB1 release and AQP4
      expression. Administration of probenecid reduced infarct size, decreased cerebral
      water content, inhibited neuronal death, and reduced inflammation in the brain 48
      h after stroke. In addition, HMGB1 release from neurons was significantly
      diminished and serum HMGB1 levels were substantially reduced following probenecid
      treatment. Moreover, AQP4 protein expression was downregulated in the cortical
      penumbra following post-stroke treatment with probenecid. These results suggest
      that probenecid, a powerful pannexin 1 channel inhibitor, protects against
      ischemic brain injury by inhibiting cerebral inflammation and edema.

PMID- 24317636
TI  - Dual masking of specific negative splicing regulatory elements resulted in
      maximal exon 7 inclusion of SMN2 gene.
AB  - Spinal muscular atrophy (SMA) is a fatal autosomal recessive disease caused by
      survival motor neuron (SMN) protein insufficiency due to SMN1 mutations. Boosting
      SMN2 expression is a potential therapy for SMA. SMN2 has identical coding
      sequence as SMN1 except for a silent C-to-T transition at the 6th nucleotide of
      exon 7, converting a splicing enhancer to a silencer motif. Consequently, most
      SMN2 transcripts lack exon 7. More than ten putative splicing regulatory elements
      (SREs) were reported to regulate exon 7 splicing. To investigate the relative
      strength of each negative SRE in inhibiting exon 7 inclusion, antisense
      oligonucleotides (AONs) were used to mask each element, and the fold increase of
      full-length SMN transcripts containing exon 7 were compared. The most potent
      negative SREs are at intron 7 (in descending order): ISS-N1, 3' splice site of
      exon 8 (ex8 3'ss) and ISS+100. Dual-targeting AONs were subsequently used to mask
      two nonadjacent SREs simultaneously. Notably, masking of both ISS-N1 and ex8 3'ss
      induced the highest fold increase of full-length SMN transcripts and proteins.
      Therefore, efforts should be directed towards the two elements simultaneously for
      the development of optimal AONs for SMA therapy. 

PMID- 24317637
TI  - Eculizumab in atypical haemolytic uraemic syndrome with severe cardiac and
      neurological involvement.
AB  - BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder
      usually caused by dysregulation of the alternative complement pathway.
      Uncontrolled complement activation results in systemic complement-mediated
      thrombotic microangiopathy (TMA) and subsequent multi-organ damage. The two most
      common extrarenal complications comprise neurological and cardiovascular
      involvement. Eculizumab, a humanised anti-C5 monoclonal antibody, has recently
      been introduced as a therapy for this condition. CASE-DIAGNOSIS/TREATMENT: A 19
      month-old child suffering from aHUS with severe neurological involvement, dilated
      cardiomyopathy and renal impairment requiring dialysis received eculizumab as
      first-line treatment, initiated within 12 h of admission, resulting in
      significant improvements in her neurological state and normalisation of cardiac
      and renal function. These positive outcomes have been sustained with fortnightly
      eculizumab therapy (at the time of writing, on-going for 1 year). No further
      complications of TMA have occurred. CONCLUSION: Severe cardiac involvement in a
      child with aHUS is an important indication for prompt, first-line treatment with
      eculizumab, resulting in rapid normalisation of cardiac function.

PMID- 24317638
TI  - Corticosteroids in tubulointerstitial nephritis.

PMID- 24317639
TI  - Impact of total sleep deprivation on behavioural neural processing of emotionally
      expressive faces.
AB  - Sleep deprivation impacts subjective mood states, but very little research has
      examined the impact on processing emotional information. In the current study, we
      investigated the impact of total sleep deprivation on neural responses to
      emotional facial expressions as well as the accuracy and speed with which these
      faces were categorized. Forty-nine participants completed two tasks in which they
      were asked to categorize emotional facial expressions as Happy, Sad, Angry, or
      Fearful. They were shown the 'full' expression of the emotions in one task and
      more subtle expressions in a second task in which expressions were 'morphed' with
      neutral faces so that the intensity of emotion varied. It was expected that sleep
      deprivation would lead to greater reactivity (indexed by larger amplitude N170
      event-related potentials), particularly for negative and more subtle facial
      expressions. In the full face task, sleep-deprived (SD) participants were
      significantly less accurate than controls (C) at identifying Sad faces and slower
      to identify all emotional expressions. P1 was smaller and N170 was larger for the
      SD compared to C group, but for all emotions, indicating generalized impairment
      in low-level visual processing. In the more difficult morphed face task, SD
      participants were less accurate than C participants for Sad faces; as well, the
      group difference in reaction time was greatest for Sad faces. For the SD group,
      N170 increased in amplitude with increasing perceptual difficulty for the Fearful
      and Angry faces, but decreased in amplitude with increasing difficulty for Sad
      faces. These data illustrate that sleep deprivation led to greater neural
      reactivity for the threat-related negative emotions as they became more subtle;
      however, there was a failure to engage these perceptual resources for the
      processing of Sad faces. Sleep loss preferentially impacted the processing of Sad
      faces; this has widespread implications for sleep-deprived groups.

PMID- 24317640
TI  - Effect of emotional and neutral declarative memory consolidation on sleep
      architecture.
AB  - The relationship between emotional or neutral declarative memory consolidation
      and sleep architecture was investigated. Thirty university students (21 females)
      viewed negative, neutral, or positive pictures and rated their valence and
      arousal in the evening. Participants performed a recognition test 1 h later and
      then underwent overnight polysomnography. Their post-encoding sleep architecture
      was compared to a baseline night. Participants returned 6 days following encoding
      for a second recognition test. Results showed no group (Negative, Neutral,
      Positive) differences in recognition 1 h or 6 days following encoding. Stage 2
      sleep spindle density decreased across all groups following encoding, and
      recognition after 6 days was positively correlated with Stage 2 sleep spindle
      density on both nights. There was no change in REM density in any of the groups.
      This is the first investigation into phasic sleep microarchitecture changes
      following emotional and neutral declarative learning. Future investigations may
      benefit from more salient emotional stimuli.

PMID- 24317642
TI  - Ego development in adolescence: Longitudinal studies.
AB  - Adolescents from four schools (one inner-city, two suburban, and one private)
      were tested two or three times using the Washington University Sentence
      Completion Test of Ego Development. Testing intervals ranged from 1.5 to 6 years.
      About half (N=193) the original pool was retested at twelfth grade. Every sample
      showed a mean rise in ego level; for six of eight samples that rise was
      statistically significant. Every pair of testings showed a postive correlation
      between scores; 10 of 14 correlations were significantly different from zero.
      Thus both test-retest correlations (about 0.5) and change scores support the
      hypothesized sequence of ego development. Significant correlation between ego
      level and intelligence occurred in two schools (0.6 at elementary and junior high
      grades and 0.4 at twelfth grade), but correlation was about zero in the private
      school. 

PMID- 24317641
TI  - Sterilization by gamma radiation of antibiotic impregnated polymethylmethacrylate
      and plaster of Paris beads. A pilot study.
AB  - INTRODUCTION: Ethylene oxide is currently recommended for sterilization of
      antibiotic impregnated beads; however this method carries health risks to
      personnel and is becoming less available. OBJECTIVE: To perform a pilot study of
      the effect of radiation for sterilization of polymethylmethacrylate (PMMA) and
      plaster of Paris (POP) beads impregnated with amikacin, enrofloxacin, and
      ceftiofur. HYPOTHESIS: Radiation would effectively sterilize the beads without
      affecting the efficacy of the antibiotic. MATERIALS AND METHODS: Beads of PMMA
      and POP were prepared in a clean but non-sterile manner with one of the three
      antibiotics (amikacin, enrofloxacin, ceftiofur) or no antibiotic. Beads were then
      exposed to radiation for a total dose of 0 kiloGray (kGy), 10 kGy and 25 kGy.
      Beads were incubated on Mueller-Hinton agar plates seeded with Escherichia coli,
      Staphylococcus aureus or Pseudomonas aeruginosa for 24 hours or cultured in brain
      heart infusion broth for 48 hours. Zones of inhibition were measured on the agar
      plates and statistics were performed on the diameters of the zones of inhibition
      using an analysis of variance. RESULTS: There were no differences in the
      diameters of inhibition for all levels of radiation for all PMMA beads. The same
      was true with POP beads with the exception of enrofloxacin which had a
      significantly decreased zone of inhibition with increased levels of radiation,
      though the clinical significance of this finding was not assessed. Only beads
      without antibiotics and not exposed to radiation had bacterial growth. CLINICAL
      SIGNIFICANCE: Radiation may be an effective method of sterilization for
      antibiotic impregnated beads.

PMID- 24317643
TI  - Transition or transformation? Personal and political development of former
      Berkeley Free Speech Movement activists.
AB  - Former Berkeley Free Speech Movement activists' sociopolitical status, self and
      ideal self constructions, perceptions of parents' child-rearing practices and
      moral reasoning were compared with an assessment made 11 years earlier following
      the Berkeley Sproul Hall sit-in. Activists were found to be less politically
      active, more tempered in their political radicalism, more pragmatic and
      personally reactive in their self and ideal self conceptualizations, more
      critical in their perceptions of parental relationships, and stable in their
      level of moral development. While activists appear to have made some important
      life transitions, an argument is made for their continued distinctiveness as a
      generational cohort both politically and psychosocially. 

PMID- 24317644
TI  - Sex differences in identity and intimacy development in college youth.
AB  - This study examined sex differences in the processes of identity and intimacy
      development among college youth. Fifty males, and 50 females were given measures
      of identity status, intimacy status, and self-esteem. Males were found to focus
      on intrapersonal aspects of identity status, intimacy status, and self-esteem.
      Males were found to focus on intrapersonal aspects of identity, females on
      interpersonal aspects. The pursuit of various identity development pathways
      affected self-esteem differentially for the two sexes. More females than males
      were found to be intimate and the achievement of intimacy seemed more closely
      related to identity in males than in females. The findins were interpreted in the
      context of Eriksonian theory, which seemed more adequate in explaining male than
      female development. 

PMID- 24317645
TI  - Sex differences in the relative importance of self-esteem, physical self
      satisfaction, and identity in predicting adolescent satisfaction.
AB  - Theoretical discussions of adolescence tend to emphasize the importance of
      physical development, self-views, and a transitional aspect of adolescence. Few
      research studies examine these variables in combination. The purpose of the
      present research was to examine the interrelationships of physical self
      satisfaction, self-esteem, and identity in addition to their ability to predict
      satisfaction with an individual's social milieu. Multiple regression analyses
      were conducted for six groups consisting of eighth-, tenth-, and twelfth-grade
      males and females. While the prediction patterns yielded no differences for grade
      level, differences between males and females were found. Self-esteem was the best
      predictor for males, while identity and physical self-satisfaction were the best
      predictors for females. 

PMID- 24317647
TI  - Variables influencing the dating adjustment of university students.
AB  - The author wished to determine the effect of selected variables on dating
      adjustment. Questionnaires were administered to 200 males and 130 females in
      introductory social science classes at a midwestern university. The results of
      stepwise regression indicated that the variables of frequency, commitment, and
      age of initial dating were the strongest influences on the dating adjustment of
      both sexes. Social orientation was found to be significant for the dating
      adjustment of males but not of females. 

PMID- 24317646
TI  - Hallucinogenic dependency during adolescence as a defense against homosexual
      fantasies: A reenactment of the first separation-individuation phase in the
      course of treatment.

PMID- 24317648
TI  - The relationship between identity status, locus of control, and ego development.
AB  - Based upon the assumption that identity status, locus of control, and ego stage
      development are interrelated psychological mechanisms that screen and filter
      social stimuli, a comparison of the three psychological constructs was completed
      using 294 college students. Identity achievement students were found to be more
      advanced in their ego stage development and level of internality, while diffusion
      students were less advanced. Contrary to expectations, no evidence was found for
      intraindividual development based upon cross-sectional data. 

PMID- 24317649
TI  - Drug and alcohol use, delinquency, and vandalism among upper middle class pre-
      and post-adolescents.
AB  - This article analyzes data from a survey research study of students in the fifth
      through twelfth grades of an upper middle class Chicago suburban community. The
      findings indicate the use of alcohol and drugs among both prepubertal and teenage
      students, and the involvement of both groups in theft and vandalism. The level of
      community affluence and quality of community institutions and services rule out
      the explanations ("the tangle of pathology") usually offered in studies of
      delinquency in lower class and low-income communities. Peer group pressures and
      psychogenic factors appear to influence these kinds of acting-out behavior. And
      since considerable numbers of students noted that their parents had not
      established certain important regulations for them, the view advanced by this
      study is that deficient socialization and inadequate parenting also appear to be
      causes of these behavioral problems. However, since the study did not categorize
      the data in a way to permit cross-tabulations either supporting or invalidating
      this argument, this conclusion is a tentative one. It is suggested that future
      research dealing with these problems among this social stratum investigate the
      influence of parenting on acting-out behavior. 

PMID- 24317650
TI  - Flash-induced proton transfer in photosynthetic bacteria.
AB  - A proton electrochemical potential across the membranes of photosynthetic purple
      bacteria is established by a light-driven proton pump mechanism: the absorbed
      light in the reaction center initiates electron transfer which is coupled to the
      vectorial displacement of protons from the cytoplasm to the periplasm. The
      stoichiometry and kinetics of proton binding and release can be tracked directly
      by electric (glass electrodes), spectrophotometric (pH indicator dyes) and
      conductimetric techniques. The primary step in the formation of the transmembrane
      chemiosmotic potential is the uptake of two protons by the doubly reduced
      secondary quinone in the reaction center and the subsequent exchange of
      hydroquinol for quinone from the membrane quinone-pool. However, the proton
      binding associated with singly reduced promary and/or secondary quinones of the
      reaction center is substoichiometric, pH-dependent and its rate is
      electrostatically enhanced but not diffusion limited. Molecular details of
      protonation are discussed based on the crystallographic structure of the reaction
      center of purple bacteriaRb. sphaeroides andRps. viridis, structure-based
      molecular (electrostatic) calculations and mutagenesis directed at protonatable
      amino acids supposed to be involved in proton conduction pathways. 

PMID- 24317651
TI  - Photosynthesis, photoinhibition and low temperature acclimation in cold tolerant
      plants.
AB  - Cold acclimation requires adjustment to a combination of light and low
      temperature, conditions which are potentially photoinhibitory. The photosynthetic
      response of plants to low temperature is dependent upon time of exposure and the
      developmental history of the leaves. Exposure of fully expanded leaves of winter
      cereals to short-term, low temperature shiftsinhibits whereas low temperature
      growthstimulates electron transport capacity and carbon assimilation. However,
      the photosynthetic response to low temperature is clearly species and cultivar
      dependent. Winter annuals and algae which actively grow and develop at low
      temperature and moderate irradiance acquire a resistance to irradiance 5- to 6
      fold higher than their growth irradiance. Resistance to short-term
      photoinhibition (hours) in winter cereals is a reflection of the increased
      capacity to keep QA oxidized under high light conditions and low temperature.
      This is due to an increased capacity for photosynthesis. These characteristics
      reflect photosynthetic acclimation to low growth temperature and can be used to
      predict the freezing tolerance of cereals. It is proposed that the enhanced
      photosynthetic capacity reflects an increased flux of fixed carbon through to
      sucrose in source tissue as a consequence of the combined effects of increased
      storage of carbohydrate as fructans in the vacuole of leaf mesophyll cells and an
      enhanced export to the crown due to its increased sink activity. Long-term
      exposure (months) of cereals to low temperature photoinhibition indicates that
      this reduction of photochemical efficiency of PS II represents a stable, long
      term down regulation of PS II to match the energy requirements for CO2 fixation.
      Thus, photoinhibition in vivo should be viewed as the capacity of plants to
      adjust photosynthetically to the prevailing environmental conditions rather than
      a process which necessarily results in damage or injury to plants. Not all cold
      tolerant, herbaceous annuals use the same mechanism to acquire resistance to
      photoinhibition. In contrast to annuals and algae, overwintering evergreens
      become dormant during the cold hardening period and generally remain susceptible
      to photoinhibition. It is concluded that the photosynthetic response to low
      temperatures and susceptibility to photoinhibition are consequences of the
      overwintering strategy of the plant species. 

PMID- 24317652
TI  - Characterization of a Photosystem II core and its three-dimensional crystals.
AB  - A photosystem II core from spinach containing the chlorophyll-binding proteins 47
      kDa, 43 kDa, the reaction center proteins D1, D2 and cytochromeb 559 and three
      low molecular weight polypeptides (MW < 10 kDa) was isolated, its three
      dimensional crystals were prepared, and both core and crystals were studied by
      spectroscopic techniques and electron microscopy. The absorption spectra of the
      crystallized form of the core indicate a specific orientation of the various
      pigments within the crystal. 

PMID- 24317653
TI  - Electron transport, Photosystem-2 reaction centers and chlorophyll-protein
      complexes of thylakoids of drought resistant and sensitive Lupin piants.
AB  - Two genotypes ofLupinus albus L., resistant and susceptible to drought, were
      subjected to water deficiency for up to two weeks. Such treatment progressively
      lowered the leaf water content from about 85% to about 60% (water potential from 
      0.8 to -4.3 MPa). Light-saturation curves of the uncoupled electron transport
      were analyzed according to a simple kinetic model of separated or connected
      reversible photoreactions. It gives an extrapolated maximum rate (Vmax) and the
      efficiency for capturing light (Im, which is the light intensity at Vmax/2). For
      Photosystem 2, Vmax and, less markedly, Im, declined with increasing severity of
      drought treatment; the artificial donor, diphenylcarbazide, could not restore the
      activity. One cause of this Photosystem 2 inhibition could be the loss of active
      Photosystem 2 centers. Indeed, their concentration relative to chlorophyll,
      estimated by flash-induced reduction of dimethylquinone, was halved by a medium
      stress. To the extent that it was still not restored by diphenylcarbazide, the
      site of Photosystem 2 inactivation must have been close to the photochemical
      trap, after water oxidation and before or at plastoquinone pool. By relating
      electron transport rate to active centers instead of chlorophyll, no inhibition
      by drought was detected. Therefore, water stress inactivates specifically
      Photosystem 2, without impairing a downhill thermal step of electron transport.
      On the other hand, the decrease of Im suggests that antennae connected to
      inactive centers may transfer their excitation energy to active neighbors, which
      implies that antenna network remains essentially intact. Gel electrophoresis
      confirmed that the apoproteins of the pigment complexes were well conserved. In
      conclusion, the inactivation of Photosystem 2 may not be a physical loss of its
      centers and core antennae but probably reflects protein alterations or
      conformational changes. These may result from the massive decrease of lipids
      induced by drought (Meyer et al. 1992, Photosynth. Res. 32: 95-107). Both lupin
      genotypes behaved similarly but, for a same deficiency, the resistant seemed
      unexpectedly more sensitive to drought. 

PMID- 24317654
TI  - IsProchlorothrix hollandica the best choice as a prokaryotic model for higher
      plant Chla/b photosynthesis?
AB  - We examine the issue of prochlorophyte origins and provide analyses which
      highlight the limitations of inferring evolutionary trees from anciently diverged
      sequences that have markedly different GC contents. Under these conditions we
      have found that current tree reconstruction methods strongly group together
      sequences with similar GC contents, whether or not the sequences share a common
      ancestor. We provide 3'psbA termini sequence forProchloron didemni and find it
      does not have the 7 amino acid deletion that occurs in Chla/b chloroplasts
      andProchlorothrix hollandica. This is consistent with the recent findings of a
      Chlc like pigment in the light harvesting system in other prochlorophytes but
      apparently absent inP. hollandica. From these observations we suggest thatP.
      hollandica is the prochlorophyte most closely related to Chla/b containing
      chloroplasts and hence the most appropriate prokaryotic model for higher plant
      Chla/b photosynthesis. 

PMID- 24317655
TI  - Intact chloroplasts display pH 5 optimum of O2-reduction in the absence of methyl
      viologen: Indirect evidence for a regulatory role of superoxide protonation.
AB  - The pH-dependence of light-driven O2-reduction in intact spinach chloroplasts is
      studied by means of chlorophyll fluorescence quenching analysis and polarographic
      O2-uptake measurements. Most experiments are carried out in presence of KCN,
      which blocks activities of Calvin cycle, ascorbate peroxidase and superoxide
      dismutase. pH is varied by equilibration with external buffers in presence of
      nigericin. Vastly different pH-optima for O2-dependent electron flow are observed
      in the presence and absence of the redox catalyst methyl viologen. Both
      fluorescence quenching analysis and O2-uptake reveal a distinct pH 5 optimum of
      O2-reduction in the absence of methyl viologen. In the presence of this catalyst,
      O2-reduction is favoured in the alkaline region, with an optimum around pH 8,
      similar to other types of Hill reaction. It is suggested that in the absence of
      methyl viologen the extent of irreversibility of O2-reduction is determined by
      the rate of superoxide protonation. This implies that O2-reduction takes place
      within the aprotic phase of the thylakoid membrane and that superoxide
      reoxidation via oxidized PS I donors competes with protonation. Superoxide
      protonation is proposed to occur at the internal surface of the thylakoid
      membrane. There is no competition between superoxide reoxidation and protonation
      when in the presence of methyl viologen the site of O2-reduction is shifted into
      the protic stroma phase. In confirmation of this interpretation, fluorescence
      measurements in the absence of KCN reveal, that non-catalysed O2-dependent
      electron flow is unique in beingstimulated by the transthylakoidal pH-gradient.
      On the basis of these findings a major regulatory role of O2-dependent electron
      flow under excess light conditions is postulated. 

PMID- 24317656
TI  - A facile method to determine the CO2/O 2 specificity factor for ribulose
      bisphosphate carboxylase/oxygenase.
AB  - A rapid method to determine the CO2/O2 specificity factor of ribulose 1,5
      bisphosphate carboxylase/oxygenase is presented. The assay measures the amount of
      CO2 and O2 fixation at varying CO2/O2 ratios to determine the relative rates of
      each reaction. CO2 fixation is measured by the incorporation of the moles
      of(14)CO2 into 3-phosphoglycerate, while O2 fixation is determined by subtraction
      of the moles of CO2 fixed from the moles of RuBP consumed in each reaction. By
      analyzing the inorganic phosphate specifically hydrolyzed from RuBP under
      alkaline conditions, the amount of RuBP present before and after catalysis by
      rubisco can be determined. 

PMID- 24317658
TI  - Variation patterns of parthenogenetic plants derived from "unreduced" embryo-sacs
      of Solanum tuberosum subspecies andigena (Juz. et Buk.) Hawkes.
AB  - Parthenogenetic seed induction was performed on one clone of Solanum tuberosum
      subspecies andigena (2n=4x=48) using S. phureja (2n=2x=24) marker inducer clones.
      The parthenogenetic population when grown was found to contain both diploid and
      tetraploid individuals presumably arising from reduced and unreduced gametes,
      respectively. Variation patterns in the diploid and tetraploid sub-populations,
      as well as a population obtained by selfing the parental clone, were compared to
      try and elucidate the origin of the tetraploid parthenotes. From the results of
      this one generation it appeared that the tetraploid parthenogenetic plants had
      been produced by a mechanism equivalent to second division restitution (SDR). 

PMID- 24317657
TI  - Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro
      generated insulin-secreting cells.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually
      resulting from autoimmune-mediated beta-cell destruction requiring lifetime
      exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising
      therapy. We present our experience of treating IDDM with co-infusion of in vitro
      autologous adipose tissue-derived MSC-differentiated insulin-secreting cells
      (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board
      approved prospective non-randomized open-labeled clinical trial after informed
      consent from ten patients. ISC were differentiated from autologous adipose tissue
      derived MSC and were infused with bone marrow-derived HSC in portal, thymic
      circulation by mini-laparotomy and in subcutaneous circulation. Patients were
      monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin
      (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration
      was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and
      PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 * 10(4) cells/MUL
      were infused. No untoward effects were observed. Over a mean follow-up of 31.71
      months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of
      0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international
      units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99
      to 6.72%. Mean GAD antibodies were positive in all patients with mean of 331.10
      IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with
      HSC represents a viable novel therapeutic option for IDDM.

PMID- 24317659
TI  - The inheritance of diastatic power and alpha-amylase contents in spring barley.
AB  - In a diallel cross of 13 spring barley varieties, non-allelic interactions
      interfered with the analysis of diastatic power. Regression of W r on V r was
      less than unity both in the full experiment and in the sub-set of two-row
      varieties. The simple additive-dominance model was adequate for the analysis of
      alpha-amylase. Regression of W r on V r indicated directional dominance,
      increasing alphaamylase. For both characters non-additive variance was detected
      and the effects of directional dominance, asymmetry of gene distribution and SCA
      were evident. Significant GCA effects were also present. No serious obstacles to
      the improvement of either character in adapted two-row varieties were apparent. 

PMID- 24317660
TI  - Mutant allele frequencies and genetic distance relationships in domestic cat
      populations of lower Egypt and the eastern Mediterranean.
AB  - Gene frequency surveys conducted in Alexandria and Cairo reveal genetic profiles
      which are extensions of those that characterize the cat populations of European
      cities. For nine selected comparisons with Alexandria, regression analysis
      indicates that a linear function best describes the relationship between Nei's
      and Cavalli-Sforza's genetic distance indices and geographic distance. 

PMID- 24317661
TI  - Linkage relationships between regulatory and structural gene loci involved in
      zein synthesis in maize.
AB  - The synthesis of at least 15 zein polypeptides is under the control of regulatory
      gene loci. One of these, Opaque-2 (chromosome 7, position 16) strongly reduces
      the zein accumulation without modifying the zein molecular components. The
      linkage relationship between the regulatory gene 02 and the 5 structural loci
      (Zp1, Zp2, Zp3, Zp6, Zp12) segregating with sample Mendelian ratios have been
      studied. Zp1, Zp2, Zp3 are closely linked to each other; moreover this gene
      cluster is located on chromosome 7 at 5.5 cM from the Opaque-2 locus. The
      structural loci Zp6 and Zp12 are not linked with each other, with the 02 locus or
      with Zp1, Zp2, Zp3. From our data it follows that the zein structural genes are
      located in at least three positions on the maize genome. The scattering in the
      genome of the genes controlled by the Opaque-2 locus suggests a transacting role
      for this regulatory element. 

PMID- 24317662
TI  - The possible role of genome activity changes in the sex determination of Daphnia
      pulex.
AB  - Sex-dependent differences in the state of the nuclear chromatin of somatic cells
      were found in Daphnia pulex. It is suggested that the genome of Daphnia pulex has
      two developmental programmes based on identical chromosome sets. The female
      programme consistently functions under a wide range of ecological conditions,
      whereas the male programme is turned on by specific ecological stimuli. The genes
      controlling the activation and function of the male programme may be
      phenotypically latent for many parthenogenetic generations. 

PMID- 24317663
TI  - Assessment of genomic and species relationships in Triticum and Aegilops by PAGE
      and by differential staining of seed albumins and globulins.
AB  - Endosperm protein components from common bread wheats (Triticum aestivum L.) and
      related species were extracted with aluminum lactate, pH 3.2, and examined by
      electrophoresis in the same buffer. Electrophoretic patterns of the albumins and
      globulins were compared to evaluate the possibility that a particular species
      might have contributed its genome to tetraploid or hexaploid wheat. Together with
      protein component mobilities, differential band staining with Coomassie Brilliant
      Blue R250 was employed to test the identity or non-identity of bands. Eight
      species and 63 accessions, representative of Triticum and Aegilops were tested.
      Considerable intraspecific variation was observed for patterns of diploid but not
      for tetraploid or hexaploid species. Patterns of some accessions of Triticum
      urartu agreed closely with major parts of the patterns of Triticum dicoccoides
      and T. aestivum. A fast-moving, green band was found in all accessions of T.
      urartu and of Triticum boeoticum, however, that was not found in those of T.
      dicoccoides or T. aestivum. This band was present in all accessions of Triticum
      araraticum and Triticum zhukovskyi. Patterns of Aegilops longissima, which has
      been suggested as the donor of the B genome, differed substantially from those of
      T. dicoccoides and T. aestivum. Finally, two marker proteins of intermediate
      mobility were also observed and may be used to discriminate between accessions of
      T. araraticum/T. zhukovskyi and those of T. dicoccoides/T. aestivum. 

PMID- 24317665
TI  - Effects of osmotic stress on polar auxin transport in Avena mesocotyl sections.
AB  - Segments of mesocotyls of Avena sativa L. transported [1-(14)C]indol-3yl-acetic
      acid (IAA) with strictly basipetal polarity. Treatment of the segments with
      solutions of sorbitol caused a striking increase in basipetal auxin transport,
      which was greatest at concentrations around 0.5 M. Similar effects were observed
      with mannitol or quebrachitol as osmotica, but with glucose or sucrose the
      increases were smaller. Polar transport was still detectable in segments treated
      with 1.2 M sorbitol. The effects of osmotic stress on the polar transport of
      auxin were reversible, but treatment with sorbital solutions more concentrated
      than 0.5 M reduced the subsequent ability of mesocotyl segments to grow in
      response to IAA. The increased transport of auxin in the osmotically stressed
      segments could not be explained in terms of an increased uptake from donor
      blocks. The velocity of transport declined with higher concentrations of
      osmoticum. The reasons for the enhancement of auxin transport by osmotic stress
      are not known. 

PMID- 24317664
TI  - Folivory affects composition of nectar, floral odor and modifies pollinator
      behavior.
AB  - Herbivory induces changes in plants that influence the associated insect
      community. The present study addresses the potential trade-off between plant
      phytochemical responses to insect herbivory and interactions with pollinators. We
      used a multidisciplinary approach and have combined field and greenhouse
      experiments to investigate effects of herbivory in plant volatile emission,
      nectar production, and pollinator behavior, when Pieris brassicae caterpillars
      were allowed to feed only on the leaves of Brassica nigra plants. Interestingly,
      volatile emission by flowers changed upon feeding by herbivores on the leaves,
      whereas, remarkably, volatile emission by leaves did not significantly differ
      between infested and non-infested flowering plants. The frequency of flower
      visits by pollinators was generally not influenced by herbivory, but the duration
      of visits by honeybees and butterflies was negatively affected by herbivore
      damage to leaves. Shorter duration of pollinator visits could be beneficial for a
      plant, because it sustains pollen transfer between flowers while reducing nectar
      consumption per visit. Thus, no trade-off between herbivore-induced plant
      responses and pollination was evident. The effects of herbivore-induced plant
      responses on pollinator behavior underpin the importance of including ecological
      factors, such as herbivore infestation, in studies of the ecology of plant
      pollination. 

PMID- 24317666
TI  - Kinetic characterization of N-1-Naphthylphthalamic acid binding sites from maize
      coleoptile homogenates.
AB  - The association of NPA with particulate material from corn coleoptile homogenates
      and the dissociation of the complexes formed are characterized. Using a
      filtration method, a single rate constant for the association at 0 degrees  C was
      determined as 2.7*10(-6) M(-1) min(-1), and for the dissociation of the complex a
      rate constant of 0.086 min(-1) was obtained with the same method. From these a
      dissociation constant of the complex of 3.4*10(-8) M can be calculated, which is
      in good agreement with the dirct determination of this constant in equilibrium
      measurements. This is taken as an indication for a simple reaction schema
      describing the reaction of NPA with its particle-bound receptor, and it can be
      inferred that membrane permeation does not impose a limitation on this reaction
      under the conditions used in this investigation. This view is strengthened by the
      absence of any indication for a carrier mechanism in "counterflow" experiments. A
      few minor deviations from quantitative predictions of the simple binding reaction
      schema are discussed. 

PMID- 24317667
TI  - Fractionation of particulate material from maize coleoptile homogenates with
      polyethylene glycol.
AB  - Polyethyleneglycol (PEG) has been used to sediment particulate material from
      maize coleoptile homogenates at low centrifugal forces. The resuspended sediments
      were used for N-1-naphthylphthalamic acid (NPA)-binding studies. Binding activity
      was influenced by monovalent cations in the resuspension medium, but even at
      concentrations of up to 1.2 M NaCl or 0.5 M LiCl or CsCl, half of the binding
      activity was still recovered. Binding activity was influenced by divalent
      cations, because it decreased when Ca(2+) and Mg(2+) ions in the medium were
      complexed with EDTA. Fractionated sedimentation using increasing concentrations
      of PEG resulted in two peaks of NPA-binding activity at about 3% and 6% PEG. The
      3% peak cintained enzymatic markers for mitochondria and endoplasmatic reticulum
      while the 6% peak contained NPA-binding activity only. Possible explanations for
      the bimodal distribution of NPA binding after fractionated PEG precipitation are
      discussed. 

PMID- 24317668
TI  - Photosynthetic apparatus in chilling-sensitive plants : V. Changes in protein
      fractions of leaves and isolated chloroplasts following cod and dark storage and
      illumination of tomato leaves.
AB  - Proteins of fresh, cold and dark-stored and illuminated tomato leaves were
      fractionated by SDS electrophoresis. The total soluble proteins extracted from
      fresh leaves were separated into 5 main fractions with MWs of 54,000, 45,000,
      32,000, 23,000 and 14,000. The cold and dark storage of the leaves causes a
      marked reduction mainly in the fraction with MW of 45,000 which increased with
      the illumination of the cold and dark-storaged leaves. The polypeptides with MWs
      of 54,000 and 14,000 (probably large and small subunits of ribulose, bisphosphate
      carboxylase) were stable under these conditions. In contrast, the polypeptides
      with MWs of 54,000 and 14,000 are decreased following the storage of tomato
      leaves in the dark at room temperature. Chloroplast soluble proteins were
      seperated by SDS electrophoresis into fractions with MWs of 64,000, 54,000,
      20,000 and 14,000. The same fractions in similar proportions were observed in
      soluble-chloroplast proteins from fresh as well as coold and dark-stored and
      illuminated leaves. No drastic changes in structural polypeptides were observed
      following cold and dark-storage and illumination of the leaves. The results
      indicated that the main protein fraction, which degradated following cold and
      dark storage of tomato leaves and synthetized during illumination, is the
      fraction of cytoplasmic protein which in SDS electrophoresis gives polypeptides
      of about 45,000 MW. The fractions of chloroplast proteins were stable under such
      conditions. 

PMID- 24317670
TI  - Synchronisation of cell division in the shoot apex of Silene in relation to
      flower initiation.
AB  - In plants of Silene coeli-rosa, induced to flower by 7 LD, synchronisation of
      cell division in 20 per cent or more of the cells in the shoot apical dome was
      found on the 8th and 9th days after the beginning of induction, during the
      plastochron before sepal initiation. Synchronisation was inferred from the
      changes in the proportions of cells with the 2C and 4C amounts of DNA, and
      changes in mitotic index and labelling index. From the peaks of mitotic index a
      cell cycle of 10 h was measured for the synchronised cells, half that of cells in
      the apices of uninduced plants in short days. The faster cell cycle and
      synchronisation in the induced plants was associated with a shortening, of both
      G1 and G2, suggesting two control points, while S and M remained unchanged. These
      results are compared with those from other plants in which synchronisation occurs
      at the beginning rather than the end of evocation. 

PMID- 24317669
TI  - Photosynthetic apparatus in chilling-sensitive plants : VI. Cold and dark-induced
      changes in chloroplast superoxide dismutase activity in relation to loosely-bound
      manganese content.
AB  - Both total and CN-insensitive superoxide dismutase (SOD) activities in relation
      to the level of manganese were studied in chloroplasts and digitonin
      subchloroplast particles obtained from fresh, cold and dark-stored, and
      illuminated leaves of Licopersicon esculentum, Mill. Following cold and dark
      treatment of detached leaves and intact plants, both total SOD activity and Mn
      content were greatly diminished while illumination of the leaves (2 h, 8,000 lx,
      25 degrees  C) resulted in a large increase of Mn content and a partial
      restoration, of SOD activity. When growing plants were kept for 3-4 days in the
      dark, either at 0 degrees  C or 25 degrees  C, a decrease in chloroplast SOD
      activity, Mn content, and Hill reaction was also observed. However, with a
      prolonged dark treatment either at 0 degrees  C or at 25 degrees  C, there was a
      slight increase in chloroplast Mn content accompanied by an enhancement of both
      SOD and Hill reaction activities, suggesting that even in the dark some
      translocation of Mn from cytosol into chloroplasts may occur. Hypotonically
      treated chloroplasts and digitonin subchloroplast particles contained almost
      exclusively CN-insensitive, SOD activity, while Tris-washed chloroplast
      preparations were completely deprived of SOD activity. All these data seem to
      indicate that a chloroplast loosely-bound Mn pool is involved in CN-insensitive
      SOD activity. 

PMID- 24317671
TI  - Nucleotide pyrophosphatase activity in dry and germinated seeds of Triticum, and
      its relationship to general acid phosphatase activity.
AB  - A cytochemical investigation has been made of nucleotide pyrophosphatase activity
      in dry and germinated seeds of Triticum, and its distribution compared to that of
      general acid phosphatase reactions seen with naphthol AS-BI phosphate and p
      nitrophenylphosphate as substrates. Acid phosphatase activity was present in the
      cytoplasm and in channels through the walls of the aleurone cells in both dry and
      germinated seeds. The cytoplasmic activity was even more marked with nucleotide
      pyrophosphatase which was almost entirely absent from the cell walls. Nucleotide
      pyrophosphatase was active in all endosperm cells but particularly in some cells
      adjacent to the aleurone layer. In addition, all cells of the scutellum and
      embryo were positive for nucleotide pyrophosphatase activity, especially the
      developing fibres and xylem elements of leaves and coleoptiles, mature leaf xylem
      and phloem elements, scutellar provascular and vascular tissues and the epidermis
      of dark grown coleoptiles. 

PMID- 24317672
TI  - Regeneration of vascular tissue in wounded pea roots.
AB  - Severance of the stele of young main roots of pea (Pisum sativum L.) results in
      formation of a bridge of vascular tissue in the remaining cortex. Cell divisions
      occur close to the severed vascular tissues on both the proximal and distal sides
      of the cut within 24 h. Differentiation of new vascular strands subsequently
      begins in the same locations and progresses from both sides of the wound into the
      remaining cortex and also back along the original vascular strands. Most of the
      vascular tissue which forms the bridge through the cortex differentiates in the
      acropetal direction. Continuous strands composed of single sieve elements bypass
      the wound somewhat sooner than the first complete xylem strands; the latter in 60
      70% of the cases, are present by 3 d. Cambial activity subsequently adds more
      xylem and phloem. Vascular regeneration is not affected by removal of the
      epicotyl or the root tip; it is greatly reduced but not prevented by removal of
      the cotyledons. 

PMID- 24317673
TI  - Stem growth, flower formation, and endogenous gibberellins in a normal and a
      dwarf strain of Silene armeria.
AB  - The physiological basis of dwarfism in a single-gene, recessive mutant of Silene
      armeria L. was investigated through comparison with a normal strain. Exposure of
      the normal strain to long days led to stem growth and flower formation while
      similar exposure of the dwarf strain led only to flowering, with very little stem
      growth. Application of gibberellin A3 or A4+7 in short days promoted stem
      elongation in the normal strain, but had a much lesser effect in the dwarf
      strain. Upon extraction and chromatographic fractionation of the endogenous
      gibberellins (GAs) in the normal strain of S. armeria, three zones of GA activity
      were found. An increase in one zone of activity was found in both strains after 1
      long day. Neither the quality nor the quantity of the extractable GAs differed
      greatly between the dwarf and the normal strain. Vegetative dwarf scions, grafted
      onto fully induced, normal stocks formed flowers, but their growth habit was not
      changed. Thus, the lack of stem growth in response to long days in the dwarf
      strain appears to result from a lack of GA sensitivity in the stem tissue of
      these plants. However, during flower formation dwarf plants did exhibit
      elongation of the peduncles. This response was suppressed by the growth retardant
      2-isopropyl-4-dimethylamino-5-methylphenyl-1-piperidine-carboxylate methyl
      chloride (AMO-1618), and applied GA3 could partially overcome this inhibition.
      Thus, peduncle elongation in the dwarf strain appears to be regulated by
      endogenous GAs. 

PMID- 24317674
TI  - Effect of light on the development of glyoxysomal functions in the cotyledons of
      mustard (Sinapis alba L.) seedlings.
AB  - The degradation of storage fat in the cotyledons of mustard seedlings is
      unaffected by phytochrome and photosynthesis (irradiation with continuous red or
      far-red light from sowing of the seeds) although light imposes a strong
      constraint on the translocation of organic matter from the cotyledons into the
      seedling axis. Likewise, the development and disappearance of glyoxysomal enzyme
      activities (isocitrate lyase, malate synthase, citrate synthase) takes place
      independently of light. It is concluded that the mobilization of storage fat (fat
      >carbohydrate transformation) is independent of photomorphogenesis. The surplus
      of carbohydrate produced from fat in the light seems to be converted to starch
      grains in the plastids, which function as a secondary storage pool in the
      cotyledons. 

PMID- 24317675
TI  - Flowering in Vitis: Conversion of tendrils into inflorescences and bunches of
      grapes.
AB  - Inflorescences and fruits with viable seeds were produced in place of tendrils in
      plants of Vitis vinifera L. cv. "Muscat of Alexandria" and in a staminate hybrid
      grapevine (Vitis vinifera x V. rupestris Scheele) following repeated applications
      of 10-20 MUl of 50-200 MUM 6-(benzylamino)-9-(2-tetrahydropyranyl)-9H-purine
      (PBA) to apices. Young leaves, shoot tips and axillary buds were removed before
      the PBA treatments were commenced. The number and weight of berries produced by
      inflorescences derived from tendrils was closely correlated with the number and
      area of leaves retained. When application of PBA was continued after floral
      initiation there was formation of fused flowers and cleistogamous pollination. 

PMID- 24317676
TI  - Distribution of lectins in membranes of soybean and peanut plants : I. General
      distribution in root, shoot and leaf tissue at different stages of growth.
AB  - The distribution of lectin activity in soybean and peanut plants has been
      investigated. In both plants activity is found in all tissues examined (roots,
      shoots and leaves) at all stages of development from seedling to maturity (7
      weeks). The cellular location of the lectins differs between soybean and peanut:
      in soybean the lectins are generally membrane-associated, whereas in peanut
      plants lectin activity is present also in the soluble cytoplasmic fraction. The
      membrane-associated lectins appear to differ from the seed lectins of the
      respective plants. The function of membrane-associated lectins is discussed. 

PMID- 24317677
TI  - Polyribosomes in protoplasts isolated from tobacco leaves.
AB  - Polyribosomes (polysomes), active in an amino acid incorporation system in vitro,
      were isolated from tobacco leaf protoplasts. A comparison of polysome profiles
      indicated that the polysome/monosome ratio is greatly decreased in isolated
      protoplasts as compared to the intact leaf. In isolated protoplasts, a marked
      accumulation of ribosomal subunits was also found. The division of protoplasts,
      as investigated in the 8-cell and callus stages, was associated with a(n) (at
      least) partial regeneration of polysome profiles characteristic for leaves.
      Plasmolysis of leaves attached to the plant had no great effect on the polysome
      profile. However, leaf excision per se resulted in a dramatic loss of polysomes,
      even when the leaf tissue was floated on water. It is concluded that the
      isolation of the cell from its normal environment, and not the osmotic stress and
      associated increase in RNase activity, is the most important factor responsible
      for the loss of polysomes in isolated protoplasts. 

PMID- 24317678
TI  - Callus and shoot formation in organ and tissue cultures of Hedera helix L.,
      English ivy.
AB  - Whole embryos and organs excised from ungerminated embryos and from seedlings of
      H. helix were cultured to assess their capacity to form callus and regenerate
      organs. There is a high potential for shoot formation in the explanted cotyledons
      and in the explanted hypocotyl of the ungerminated embryo. Whole embryos and
      explanted organs from seedlings produced callus rather than organized structures.
      In contrast to the excised embryo organs, embryo-derived callus had very low
      organogenetic potential. 

PMID- 24317679
TI  - Erratum.

PMID- 24317681
TI  - Continuous positive airway pressure treatment improves cardiovascular outcomes in
      elderly patients with cardiovascular disease and obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is associated with the progression of
      cardiovascular disease (CVD), particularly in the middle-aged population.
      However, the clinical importance of OSA as a risk for CVD in the elderly
      population remains controversial. Moreover, evidence for the effectiveness of
      continuous positive airway pressure (CPAP) treatment for the secondary prevention
      of CVD in elderly patients is lacking. We assessed whether CPAP treatment
      improves cardiovascular outcomes in elderly patients with OSA and CVD. In this
      retrospective cohort study, we enrolled 130 elderly patients aged 65-86 years
      with moderate to severe OSA (apnea-hypopnea index >=15/h) and a history of
      hospitalization due to CVD, who underwent polysomnography between November 2004
      and July 2011. Patients were divided into the CPAP group (n = 64) or untreated
      OSA group (n = 66). The main outcome measures were cardiovascular death and
      hospitalization due to CVD. During the mean follow-up period of 32.9 +/- 23.8
      (standard deviation) months, 28 (21.5 %) patients either died or were
      hospitalized. The Kaplan-Meier curves indicated that event-free survival was
      significantly lower in the untreated OSA group than in the CPAP group (P <
      0.005). A multivariate analysis showed that the risk was significantly increased
      in the untreated OSA group (hazard ratio 5.13; 95 % confidence interval 1.01
      42.0; P < 0.05). Moderate to severe OSA not treated with CPAP was an independent
      risk factor for relapse of a CVD event, and adequate CPAP treatment improved
      cardiovascular outcomes in elderly patients. 

PMID- 24317680
TI  - Imaging markers of structural and functional brain changes that precede cognitive
      symptoms in risk for Alzheimer's disease.
AB  - Neuroimaging has rapidly advanced investigations into dysfunction both within and
      emanating from the hippocampus in early Alzheimer's disease . Focusing on
      prodromal subjects, we will discuss structural changes to hippocampal subregions,
      alterations to functional activity both within the hippocampus and elsewhere in
      the cortex, as well as changes to structural white matter connectivity and
      changes to functionally correlated patterns during memory performance. We present
      ample evidence that asymptomatic subjects demonstrate substantial identifiable
      brain changes before the onset of cognitive decline, but suggest there is
      significant work yet to be accomplished before applying these findings to
      individual patients. 

PMID- 24317682
TI  - Silencing Dicer expression enhances cellular proliferative and invasive
      capacities in human tongue squamous cell carcinoma.
AB  - microRNAs (miRNAs) are aberrantly expressed in cancer. An enzyme essential for
      miRNA processing is Dicer, whose expression is deregulated in diverse types of
      cancer and correlates with tumor progression. However, whether the regulation of
      Dicer expression affects tongue squamous cell carcinoma is unknown. In the
      present study, we investigated how silencing the expression of Dicer alters cell
      proliferation, cell cycle patterns, and cell migration and invasion in the Tca
      8113 tongue squamous cell carcinoma cell line. Dicer expression levels were
      determined using quantitative PCR and western blot analysis in normal oral
      gingival epithelial cells and in two tongue squamous cell carcinoma lines, Tca
      8113 and UM-1. Tca-8113 cells were transfected with Dicer siRNA or a negative
      control siRNA. Cell proliferation was determined using the MTT assay and the cell
      cycle was examined using flow cytometry. Cell migration and invasion changes were
      evaluated using wound-healing, adherence and Transwell assays. Dicer was
      expressed at lower levels in the tongue squamous cell carcinoma cell lines Tca
      8113 and UM-1 compared to normal gingival epithelial cells, and less Dicer was
      expressed in UM-1 cells compared to Tca-8113 cells. Notably, Tca-8113 cells
      transfected with Dicer siRNA had significantly higher proliferative and invasive
      abilities than cells transfected with the negative control siRNA or non
      transfected cells. Silencing Dicer may promote the progression of tongue squamous
      cell carcinoma. Dicer could serve a promising biomarker and a potential
      therapeutic target for tongue squamous cell carcinoma. 

PMID- 24317683
TI  - Probing the electronic and geometric structure of ferric and ferrous myoglobins
      in physiological solutions by Fe K-edge absorption spectroscopy.
AB  - We present an iron K-edge X-ray absorption study of carboxymyoglobin (MbCO),
      nitrosylmyoglobin (MbNO), oxymyoglobin (MbO2), cyanomyoglobin (MbCN), aquomet
      myoglobin (metMb) and unligated myoglobin (deoxyMb) in physiological media. The
      analysis of the XANES region is performed using the full-multiple scattering
      formalism, implemented within the MXAN package. This reveals trends within the
      heme structure, absent from previous crystallographic and X-ray absorption
      analysis. In particular, the iron-nitrogen bond lengths in the porphyrin ring
      converge to a common value of about 2 A, except for deoxyMb whose bigger value is
      due to the doming of the heme. The trends of the Fe-Nepsilon (His93) bond length
      is found to be consistent with the effect of ligand binding to the iron, with the
      exception of MbNO, which is explained in terms of the repulsive trans effect. We
      derive a high resolution description of the relative geometry of the ligands with
      respect to the heme and quantify the magnitude of the heme doming in the deoxyMb
      form. Finally, time-dependent density functional theory is used to simulate the
      pre-edge spectra and is found to be in good agreement with the experiment. The
      XAS spectra typically exhibit one pre-edge feature which arises from transitions
      into the unoccupied dsigma and dpi - piligand* orbitals. 1s -> dpi transitions
      contribute weakly for MbO2, metMb and deoxyMb. However, despite this strong Fe d
      contribution these transitions are found to be dominated by the dipole (1s -> 4p)
      moment due to the low symmetry of the heme environment. 

PMID- 24317684
TI  - Patterns of TPD52 overexpression in multiple human solid tumor types analyzed by
      quantitative PCR.
AB  - Tumor protein D52 (TPD52) is located at chromosome 8q21, a region that is
      frequently gained or amplified in multiple human cancer types. TPD52 has been
      suggested as a potential target for new anticancer therapies. In order to analyze
      TPD52 expression in the most prevalent human cancer types, we employed
      quantitative PCR to measure TPD52 mRNA levels in formalin-fixed tissue samples
      from more than 900 cancer tissues obtained from 29 different human cancer types.
      TPD52 was expressed at varying levels in all tested normal tissues, including
      skin, lymph node, lung, oral mucosa, breast, endometrium, ovary, vulva,
      myometrium, liver, pancreas, stomach, kidney, prostate, testis, urinary bladder,
      thyroid gland, brain, muscle and fat tissue. TPD52 was upregulated in 18/29 (62%)
      tested cancer types. Strongest expression was found in non-seminoma (56-fold
      overexpression compared to corresponding normal tissue), seminoma (42-fold),
      ductal (28-fold) and lobular breast cancer (14-fold). In these tumor types, TPD52
      upregulation was found in the vast majority (>80%) of tested samples.
      Downregulation was found in 11 (38%) tumor types, most strongly in papillary
      renal cell cancer (-8-fold), leiomyosarcoma (-6-fold), clear cell renal cell
      cancer (-5-fold), liposarcoma (-5-fold) and lung cancer (-4-fold). These results
      demonstrate that TPD52 is frequently and strongly upregulated in many human
      cancer types, which may represent candidate tumor types for potential anti-TPD52
      therapies.

PMID- 24317686
TI  - Genetic Evaluation and Utilization (GEU) program : The rice improvement program
      of the International Rice Research Institute.
AB  - The Genetic Evaluation and Utilization (GEU) program of the International Rice
      Research Institute (IRRI) is an interdisciplinary program for the improvement of
      rice crops. Scientists trained in diverse disciplines such as plant breeding,
      plant pathology, entomology, agronomy, cereal chemistry, plant physiology, and
      soil chemistry work together and contribute their specialized skills to this
      joint endeavor. The program has five interrelated components: (1) germ plasm
      collection and conservation, (2) research in disciplinary areas, (3) development
      of improved germ plasm, (4) distribution, evaluation and exchange of germ plasm
      internationally, (5) training of young scientists.Over forty thousand rice
      varieties from different countries are being maintained in the IRRI germ plasm
      bank. These varieties have been screened for grain quality, resistance to various
      diseases and insects, and tolerance to various environmental stresses such as
      drought, high and low temperatures and problem soils. Donor parents for
      resistances to each of the problem areas have been identified. These parents were
      utilized for developing improved germ plasm. Varieties with resistance to as many
      as five diseases and five insect species have been developed. These multiple
      resistant varieties are grown on millions of hectares of rice land. Seeds of
      improved breeding materials are exchanged internationally and 194 scientists from
      different countries have been trained in rice improvement work. 

PMID- 24317685
TI  - Is intraductal tubulopapillary neoplasia a new entity in the spectrum of familial
      pancreatic cancer syndrome?
AB  - We report on a 78-year old male with a positive family history for pancreatic
      cancer, who underwent total pancreatectomy for a suspected intraductal papillary
      mucinous neoplasm with extensive involvement of the main pancreatic duct and
      multiple branch ducts. The post operative course was uneventful. Macroscopic
      examination of the specimen revealed multiple solid non-mucinous tumour nodules
      throughout the main pancreatic duct and within multiple branch ducts. The
      microscopic appearance of the tumour, in particular its tubulopapillary growth
      pattern and immunohistochemical mucin profile (MUC1, MUC6 positive; MUC2, MUC5AC
      negative) were consistent with intraductal tubulopapillary neoplasia (ITPN)
      showing high-grade dysplasia. No evidence of stromal invasion was identified. To
      the best of our knowledge, this is the first report on ITPN in a high-risk
      patient based on a history of familial pancreatic cancer (FPC). The potential
      association between this entity and the spectrum of neoplastic lesions in FPC
      should be investigated with particular consideration of the lower biological
      aggressiveness of ITPN.

PMID- 24317687
TI  - Absence of qualitative genes controlling interspecific pairing in rye B
      chromosomes.
AB  - The meiotic behaviour of hybrids between Secale cereale carrying B chromosomes
      and S. vavilovii has been studied in order to estimate the effects of B
      chromosomes on hybrid meiotic pairing. The possible effect of Bs on the meiotic
      pairing of the offspring from backcrosses with S. vavilovii has been studied
      also. The results obtained clearly indicate that no detectable differences
      existed in chromosome pairing of hybrids with or without B chromosomes. The
      hypothetical existence of epistatic genes on cereale genome masking the effect of
      Bs has been rejected after the results obtained in backcrosses. Therefore, lack
      of qualitative genes controlling interspecific pairing on rye B chromosomes has
      been concluded. A quantitative effect of B chromosomes was detected only when
      they were in alien cytoplasm. 

PMID- 24317688
TI  - The relative importance of prenatal and postnatal maternal influences on growth
      in mice.
AB  - The cross-nursing technique was used to assess the relative importance of
      prenatal and postnatal maternal influences on growth in mice from an unselected
      population originated from a cross of four highly inbred strains. Body weights
      were studied at birth, 7-, 14-, 21- and 42-days, in addition to the weight gains
      between these ages and tail length at 21 and 42 days of age. At littering, each
      dam in each nursing set retained two of her own offspring and two were
      transfereed to each of the other dams in the set, so that each nursed litter
      contained six young representing three mothers. Prenatal influences accounted for
      37, 15, 10, 11 and 13 % of the total variation in the respective body weights,
      while postnatal influences accounted for 0, 64, 65, 49 and 14% at the respective
      ages. In the case of weight gains, prenatal influences were responsible for 16,
      4, 6 and 30%, while postnatal influences were responsible for 66, 66, 31 and 7%
      of the total variation in gain during the respective four periods examined.
      Apparently the individual weight gain from 7 to 14 days was a better measure of
      the lactational performance of the dam than individual 14-day weight. For tail
      length, prenatal influences accounted for 6 % and 4 % of the total variation in
      tail length at 21 and 42 days, respectively, while postnatal influences accounted
      for 60 % and 24 % at the respective ages. Generally, there was no indication of
      an important interaction between the nurse and the nursed young at any stage
      studied. 

PMID- 24317689
TI  - Somatic hybridisation of Daucus carota and D. capillifolius by protoplast fusion.
AB  - Protoplasts isolated from cultured cells of albino carrot (Daucus carota) and
      normal green D. capillifolius were fused by polyethylene glycol. Selection of
      somatic hybrid plants was based on the restoration of photosynthetic function in
      hybrids. Green plantlets selected from embryo cultures were characterized on the
      basis of leaf morphology. The interspecific protoplast fusion resulted in green
      plants with leaves which were intermediate between those of the parents. The
      somatic hybrids between orange rooted carrot variety and D. capillifolius with
      long white roots produced long, white and fleshy roots. The cytological analysis
      of parasexual hybrids revealed that the chromosome number ranged from 34 to 54.
      The most frequent chromosome number was 2n = 36. Hybrids were also found with 34
      and 35 chromosomes. The somatic hybrid showed the same isoenzyme pattern of leaf
      peroxidase as D. carota. 

PMID- 24317690
TI  - The use marker alleles for the introgression of linked quantitative alleles.
AB  - It is shown that when an exotic strain and a commercial strain differ genetically
      at a quantitative locus and at an adjoining marker locus, repeated backcrosses to
      the commercial strain, retaining only backcross progeny carrying the exotic
      marker allele, will allow the effective introgression of the linked quantitative
      allele from the exotic to the commercial strain. The introgression procedure will
      be particularly effective when exotic and commercial strains differ at two nearby
      marker loci with the quantitative locus bracketed between them. The simultaneous
      introgression of a number of quantitative alleles from different exotic strains,
      and appropriate selection procedures in the intercross generations that follow
      are also considered. 

PMID- 24317691
TI  - Effectiveness of ph gene in inducing homoeologous chromosome pairing in
      agrotricum.
AB  - We observed pairing, when the ph gene was present, between wheat (Triticum
      aestivum L. em. Thell.) chromosome 4B, and an Agropyron intermedium (Host) Beauv.
      chromosome (Ai) carrying a gene resistant to wheat streak mosaic (WSM). In a
      monosomic addition polyhaploid [2n = 22 = 19' + 5B' (ph) + 4B' + Ai'], we
      recorded an average of 4.1 bivalents and 0.3 trivalents per cell. Induced
      homoeologous pairing was most effective when both 5B chromosomes carrying ph gene
      were present. Our data suggest that chromosome 4B of wheat and the Agropyron
      chromosome (Ai) carrying a gene for resistance to WSM are homoeologous and that
      it is possible to use either ph mutant or nullisomic 5B stock to induce genetic
      recombination between the two chromosomes. 

PMID- 24317692
TI  - Merging allylic carbon-hydrogen and selective carbon-carbon bond activation.
AB  - Since the nineteenth century, many synthetic organic chemists have focused on
      developing new strategies to regio-, diastereo- and enantioselectively build
      carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner.
      Ideal syntheses should use the least number of synthetic steps, with few or no
      functional group transformations and by-products, and maximum atom efficiency.
      One potentially attractive method for the synthesis of molecular skeletons that
      are difficult to prepare would be through the selective activation of C-H and C-C
      bonds, instead of the conventional construction of new C-C bonds. Here we present
      an approach that exploits the multifold reactivity of easily accessible
      substrates with a single organometallic species to furnish complex molecular
      scaffolds through the merging of otherwise difficult transformations: allylic C-H
      and selective C-C bond activations. The resulting bifunctional nucleophilic
      species, all of which have an all-carbon quaternary stereogenic centre, can then
      be selectively derivatized by the addition of two different electrophiles to
      obtain more complex molecular architecture from these easily available starting
      materials. 

PMID- 24317693
TI  - Transcranial amelioration of inflammation and cell death after brain injury.
AB  - Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent
      and deleterious to neurological function. At present, no effective treatment
      options are available, and little is known about the complex cellular response to
      TBI during its acute phase. To gain insights into TBI pathogenesis, we developed
      a novel murine closed-skull brain injury model that mirrors some pathological
      features associated with mild TBI in humans and used long-term intravital
      microscopy to study the dynamics of the injury response from its inception. Here
      we demonstrate that acute brain injury induces vascular damage, meningeal cell
      death, and the generation of reactive oxygen species (ROS) that ultimately breach
      the glial limitans and promote spread of the injury into the parenchyma. In
      response, the brain elicits a neuroprotective, purinergic-receptor-dependent
      inflammatory response characterized by meningeal neutrophil swarming and
      microglial reconstitution of the damaged glial limitans. We also show that the
      skull bone is permeable to small-molecular-weight compounds, and use this
      delivery route to modulate inflammation and therapeutically ameliorate brain
      injury through transcranial administration of the ROS scavenger, glutathione. Our
      results shed light on the acute cellular response to TBI and provide a means to
      locally deliver therapeutic compounds to the site of injury. 

PMID- 24317694
TI  - The rarity of dust in metal-poor galaxies.
AB  - Galaxies observed at redshift z > 6, when the Universe was less than a billion
      years old, thus far very rarely show evidence of the cold dust that accompanies
      star formation in the local Universe, where the dust-to-gas mass ratio is around
      one per cent. A prototypical example is the galaxy Himiko (z = 6.6), which--a
      mere 840 million years after the Big Bang--is forming stars at a rate of 30-100
      solar masses per year, yielding a mass assembly time of about 150 * 10(6) years.
      Himiko is thought to have a low fraction (2-3 per cent of the Sun's) of elements
      heavier than helium (low metallicity), and although its gas mass cannot yet be
      determined its dust-to-stellar mass ratio is constrained to be less than 0.05 per
      cent. The local dwarf galaxy I Zwicky 18, which has a metallicity about 4 per
      cent that of the Sun's and is forming stars less rapidly (assembly time about 1.6
      * 10(9) years) than Himiko but still vigorously for its mass, is also very dust
      deficient and is perhaps one of the best analogues of primitive galaxies
      accessible to detailed study. Here we report observations of dust emission from I
      Zw 18, from which we determine its dust mass to be 450-1,800 solar masses,
      yielding a dust-to-stellar mass ratio of about 10(-6) to 10(-5) and a dust-to-gas
      mass ratio of 3.2-13 * 10(-6). If I Zw 18 is a reasonable analogue of Himiko,
      then Himiko's dust mass must be around 50,000 solar masses, a factor of 100 below
      the current upper limit. These numbers are quite uncertain, but if most high-z
      galaxies are more like Himiko than like the very-high-dust-mass galaxy SDSS
      J114816.64 + 525150.3 at z ~ 6, which hosts a quasar, then our prospects for
      detecting the gas and dust inside such galaxies are much poorer than hitherto
      anticipated.

PMID- 24317695
TI  - Diversity of ageing across the tree of life.
AB  - Evolution drives, and is driven by, demography. A genotype moulds its phenotype's
      age patterns of mortality and fertility in an environment; these two patterns in
      turn determine the genotype's fitness in that environment. Hence, to understand
      the evolution of ageing, age patterns of mortality and reproduction need to be
      compared for species across the tree of life. However, few studies have done so
      and only for a limited range of taxa. Here we contrast standardized patterns over
      age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants
      and a green alga. Although it has been predicted that evolution should inevitably
      lead to increasing mortality and declining fertility with age after maturity,
      there is great variation among these species, including increasing, constant,
      decreasing, humped and bowed trajectories for both long- and short-lived species.
      This diversity challenges theoreticians to develop broader perspectives on the
      evolution of ageing and empiricists to study the demography of more species. 

PMID- 24317698
TI  - Five-year-old boy presenting with severe back pain, swelling, and refusal to
      walk.

PMID- 24317699
TI  - A 2-year-old boy with knee pain, fever, and multiple birthmarks.

PMID- 24317697
TI  - Structural basis of the alternating-access mechanism in a bile acid transporter.
AB  - Bile acids are synthesized from cholesterol in hepatocytes and secreted through
      the biliary tract into the small intestine, where they aid in absorption of
      lipids and fat-soluble vitamins. Through a process known as enterohepatic
      recirculation, more than 90% of secreted bile acids are then retrieved from the
      intestine and returned to the liver for resecretion. In humans, there are two
      Na(+)-dependent bile acid transporters involved in enterohepatic recirculation,
      the Na(+)-taurocholate co-transporting polypeptide (NTCP; also known as SLC10A1)
      expressed in hepatocytes, and the apical sodium-dependent bile acid transporter
      (ASBT; also known as SLC10A2) expressed on enterocytes in the terminal ileum. In
      recent years, ASBT has attracted much interest as a potential drug target for
      treatment of hypercholesterolaemia, because inhibition of ASBT reduces
      reabsorption of bile acids, thus increasing bile acid synthesis and consequently
      cholesterol consumption. However, a lack of three-dimensional structures of bile
      acid transporters hampers our ability to understand the molecular mechanisms of
      substrate selectivity and transport, and to interpret the wealth of existing
      functional data. The crystal structure of an ASBT homologue from Neisseria
      meningitidis (ASBT(NM)) in detergent was reported recently, showing the protein
      in an inward-open conformation bound to two Na(+) and a taurocholic acid.
      However, the structural changes that bring bile acid and Na(+) across the
      membrane are difficult to infer from a single structure. To understand the
      structural changes associated with the coupled transport of Na(+) and bile acids,
      here we solved two structures of an ASBT homologue from Yersinia frederiksenii
      (ASBTYf) in a lipid environment, which reveal that a large rigid-body rotation of
      a substrate-binding domain gives the conserved 'crossover' region, where two
      discontinuous helices cross each other, alternating accessibility from either
      side of the cell membrane. This result has implications for the location and
      orientation of the bile acid during transport, as well as for the translocation
      pathway for Na(+).

PMID- 24317700
TI  - Pediatricians and Affordable Care Act open enrollment: an opportunity to assist
      families in navigating health insurance.

PMID- 24317696
TI  - Muc5b is required for airway defence.
AB  - Respiratory surfaces are exposed to billions of particulates and pathogens daily.
      A protective mucus barrier traps and eliminates them through mucociliary
      clearance (MCC). However, excessive mucus contributes to transient respiratory
      infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and
      MUC5B are evolutionarily conserved genes that encode structurally related mucin
      glycoproteins, the principal macromolecules in airway mucus. Genetic variants are
      linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC,
      and the lasting effects of their inhibition, are unknown. Here we show that mouse
      Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the
      airways and middle ear, and for maintaining immune homeostasis in mouse lungs,
      whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in
      upper and lower airways. This defect led to chronic infection by multiple
      bacterial species, including Staphylococcus aureus, and to inflammation that
      failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was
      impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice.
      By contrast, in mice that transgenically overexpress Muc5b, macrophage functions
      improved. Existing dogma defines mucous phenotypes in asthma and chronic
      obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B
      levels either unaffected or increased in expectorated sputum. However, in many
      patients, MUC5B production at airway surfaces decreases by as much as 90%. By
      distinguishing a specific role for Muc5b in MCC, and by determining its impact on
      bacterial infections and inflammation in mice, our results provide a refined
      framework for designing targeted therapies to control mucin secretion and restore
      MCC. 

PMID- 24317701
TI  - Lateral and medial tibial plateau angles in normal dogs. An osteological study.
AB  - OBJECTIVES: To measure lateral and medial tibial plateau angle values in isolated
      canine tibiae and to compare lateral and medial tibial plateau angle values
      between dogs based on sex and breed. METHODS: Tibiae of 90 dogs from 24 different
      breeds were used. Photographs were taken of the medial and lateral aspects of the
      tibiae for measurement of the medial and lateral tibial plateau angles.
      Additionally, the medial tibial plateau angle was measured from radiographs of
      the tibiae. Two-way analysis of variance was used to test the effects of side,
      sex and breed on the medial and lateral tibial plateau angles as measured from
      photographs as well as the medial tibial plateal angles as measured from
      radiographs. The photographic and radiographic medial tibial plateau angles were
      compared by paired t-test, whereas the medial and lateral photographic tibial
      plateau angles were compared by t-test. RESULTS: When all dogs were included in
      the analysis, the difference between the mean medial tibial plateau angle (24.0
      +/- 3.19 degrees ) and the mean lateral tibial plateau angle (25.5 +/- 3.84
      degrees ) as measured from photographs was significant (p <0.05). The difference
      in the photographic medial tibial plateau angle between male and female dogs was
      significant (p <0.05), whereas the difference in the photographic lateral tibial
      plateau angle between sexes was not significant. There was a significant
      difference between the medial and lateral tibial plateau angles as measured from
      photographs in male dogs (p <0.05) but not in female dogs. Breed comparisons also
      showed significant differences for the photographic lateral tibial plateau angle
      (p <0.05). CLINICAL SIGNIFICANCE: The axial rotation of the femoral condyles on
      the tibial plateau is probably affected by the discrepancy between the medial and
      lateral tibial plateau angles, and this difference in certain breeds might
      influence the prevalence of cranial cruciate ligament disease.

PMID- 24317703
TI  - Climate factors affecting fertility after cervical insemination during the first
      months of the breeding season in Rasa Aragonesa ewes.
AB  - This study was carried out to examine the impact of several climate variables on
      the pregnancy rate after cervical artificial insemination (AI) of Rasa Aragonesa
      ewes. Data were derived from 8,977 inseminations in 76 well-managed flocks
      performed during the first month of the breeding season (July to October). The
      following data were recorded for each animal: farm, year, month of AI, parity,
      lambing-treatment interval, inseminating ram, AI technician, and climatic
      variables such as mean, maximum and minimum temperature, mean and maximum
      relative humidity, rainfall, and mean and maximum temperature-humidity index
      (THI) for each day from day 12 before AI to day 14 post-AI. Means were
      furthermore calculated for the following periods around AI (day 0): -12 to 0, -2
      to 0, AI day, 0 to 2, and 0 to 14. Logistic regression analysis indicated that
      the likelihood of pregnancy decreased when maximum temperature in the 2 days
      prior to AI was higher than 30  degrees C (by a factor of 0.81). Fertility was
      also lower for primiparous ewes and in multiparous ewes with more than five
      previous parturitions. Other factors with significant impact on fertility were
      flock, technician, inseminating ram, and a lambing-AI interval longer than 240
      days. It was concluded that the 2 days prior to AI seems to be the period when
      heat stress had the greatest impact on pregnancy rate in Rasa Aragonesa ewes.

PMID- 24317702
TI  - An outcome measure for patients with cervical myelopathy: the Japanese
      Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ):
      an average score of healthy volunteers.
AB  - BACKGROUND: An outcome measure to evaluate the neurological function of patients
      with cervical myelopathy was proposed by the Japanese Orthopaedic Association
      (JOA score) and has been widely used in Japan. However, the JOA score does not
      include patients' satisfaction, disability, handicaps, or general health, which
      can be affected by cervical myelopathy. In 2007, a new outcome measure, the
      Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire
      (JOACMEQ), which is a self-administered questionnaire, was developed. However,
      the influence of age and gender on the scores has not been fully examined. The
      purpose of this study was to establish the standard value of the JOACMEQ by age
      using healthy volunteers. METHODS: This study was conducted in 23 university
      hospitals and their affiliated hospitals from September to December 2011. The
      questionnaire included 24 questions for evaluation of physical function of the
      cervical spine and spinal cord. A total of 1,629 healthy volunteers were
      recruited for the study. The ages ranged from 20 to 89 years old. RESULTS: The
      volunteers comprised 798 men and 831 women. In the elderly healthy volunteers,
      the JOACMEQ scores decreased with age. In general, the scores for cervical spine
      function and upper/lower extremity function were retained up to the 60s, then
      decreased in the 70s and 80s. The scores for quality of life were retained up to
      the 70s; however, the score for bladder function was retained up to the 40s, then
      declined with age from the 50s to 80s. CONCLUSION: The standard values of the
      JOACMEQ by age were established. Differences in the scores were found among
      different generations. Patients with cervical myelopathy should be evaluated with
      this new self-administered questionnaire taking into account the standard values
      according to different ages.

PMID- 24317704
TI  - A randomised placebo-controlled trial of early treatment of the patent ductus
      arteriosus.
AB  - OBJECTIVE: Failure of closure of the patent ductus arteriosus (PDA) may be
      associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA
      may result in a reduction in adverse outcomes and need for later PDA closure with
      no increase in adverse effects. STUDY DESIGN: Multicentre, double-blind, placebo
      controlled randomised trial. SETTING: Three neonatal intensive care units in
      Australia. PATIENTS AND INTERVENTIONS: Eligible infants born <29 weeks were
      screened for a large PDA and received indomethacin or placebo before age 12 h.
      MAIN OUTCOME: Death or abnormal cranial ultrasound. RESULTS: The trial ceased
      enrolment early due to lack of availability of indomethacin. 164 eligible infants
      were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised
      to indomethacin and 48 to placebo. There was no difference in the main outcome
      between groups. Infants receiving early indomethacin had significantly less early
      pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less
      periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less
      likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non
      randomised infants with a small PDA were at low risk of pulmonary haemorrhage and
      had an 80% spontaneous PDA closure rate. CONCLUSIONS: Early cardiac ultrasound
      targeted treatment of a large PDA is feasible and safe, resulted in a reduction
      in early pulmonary haemorrhage and later medical treatment but had no effect on
      the primary outcome of death or abnormal cranial ultrasound. REGISTERED TRIAL:
      Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

PMID- 24317705
TI  - Are poker players all the same? Latent class analysis.
AB  - Poker is the gambling game that is currently gaining the most in popularity.
      However, there is little information on poker players' characteristics and risk
      factors. Furthermore, the first studies described poker players, often recruited
      in universities, as an homogeneous group who played in only one of the modes
      (land based or on the Internet). This study aims to identify, through latent
      class analyses, poker player subgroups. A convenience sample of 258 adult poker
      players was recruited across Quebec during special events or through advertising
      in various media. Participants filled out a series of questionnaires (Canadian
      Problem Gambling Index, Beck Depression, Beck Anxiety, erroneous belief and
      alcohol/drug consumption). The latent class analysis suggests that there are
      three classes of poker players. Class I (recreational poker players) includes
      those who have the lowest probability of engaging intensively in different game
      modes. Participants in class II (Internet poker players) all play poker on the
      Internet. This class includes the highest proportion of players who consider
      themselves experts or professionals. They make a living in part or in whole from
      poker. Class III (multiform players) includes participants with the broadest
      variety of poker patterns. This group is complex: these players are positioned
      halfway between professional and recreational players. Results indicate that
      poker players are not an homogeneous group identified simply on the basis of the
      form of poker played. The specific characteristics associated with each subgroup
      points to vulnerabilities that could potentially be targeted for preventive
      interventions. 

PMID- 24317706
TI  - Can CO2 assimilation in maize leaves be predicted accurately from chlorophyll
      fluorescence analysis?
AB  - Analysis is made of the energetics of CO2 fixation, the photochemical quantum
      requirement per CO2 fixed, and sinks for utilising reductive power in the C4
      plant maize. CO2 assimilation is the primary sink for energy derived from
      photochemistry, whereas photorespiration and nitrogen assimilation are relatively
      small sinks, particularly in developed leaves. Measurement of O2 exchange by mass
      spectrometry and CO2 exchange by infrared gas analysis under varying levels of
      CO2 indicate that there is a very close relationship between the true rate of O2
      evolution from PS II and the net rate of CO2 fixation. Consideration is given to
      measurements of the quantum yields of PS II (phi PS II) from fluorescence
      analysis and of CO2 assimilation ([Formula: see text]) in maize over a wide range
      of conditions. The[Formula: see text] ratio was found to remain reasonably
      constant (ca. 12) over a range of physiological conditions in developed leaves,
      with varying temperature, CO2 concentrations, light intensities (from 5% to 100%
      of full sunlight), and following photoinhibition under high light and low
      temperature. A simple model for predicting CO2 assimilation from fluorescence
      parameters is presented and evaluated. It is concluded that under a wide range of
      conditions fluorescence parameters can be used to predict accurately and rapidly
      CO2 assimilation rates in maize. 

PMID- 24317707
TI  - Plastocyanin: Structure and function.
AB  - The aim of this review is to analyze the current state of knowledge concerning
      the blue copper protein plastocyanin (PC) focusing on its interactions with its
      reaction partners cytochromef and P700. Plastocyanin is a 10 kD blue copper
      protein which is located in the lumen of the thylakoid where it functions as a
      mobileelectron carrier shuttling electrons from cytochromef to P700 in
      Photosystem I. PC is a typical beta-barrel protein containing a single copper
      center which is ligated to two histidines, a methionine and a cysteine in a
      distorted tetrahedral geometry. PC has two potential binding sites for reaction
      partners. Site 1 consists of the H87 ligand to the copper and Site 2 consists of
      Y83 which is surrounded by two clusters of negative charges which are highly
      conserved in higher plant PCs.The interaction of PC with cytochromef has been
      studied extensively. It is electrostatic in nature with negative charges on PC
      interacting with positive charges on cytochromef. Evidence from cross-linking,
      chemical modification, kinetics and site-directed mutagenesis studies implicate
      Site 2 as the binding site for Cytf. The interaction is thought to occur in two
      stages: an initial diffusional approach guided by electrostatic interactions,
      followed by more precise docking to form a final electron transfer complex.Due to
      the multisubunit nature of the Photosystem I complex, the evidence is not as
      clear for the binding site for P700. However, a small positively-charged subunit
      (Subunit III) of Photosystem I has been implicated in PC binding. Also, both
      chemical modification and site-directed mutagenesis experiments have suggested
      that PC interacts with P700 via Site 1. 

PMID- 24317708
TI  - The role of calcium in the pH-dependent control of Photosystem II.
AB  - pH-dependent inactivation of Photosystem (PS) II and related quenching of
      chlorophyll-a-fluorescence have been investigated in isolated thylakoids and PS
      II-particles and related to calcium release at the donor side of PS II. The
      capacity of oxygen evolution (measured under light saturation) decreases when the
      DeltapH is high and the pH in the thylakoid lumen decreases below 5.5. Oxygen
      evolution recovers upon uncoupling. The pH-response of inactivation can be
      described by a 1 H(+)-transition with an apparent pK-value of about 4.7. The
      yield of variable fluorescence decreases in parallel to the inactivation of
      oxygen evolution. pH-dependent quenching requires light and can be inhibited by
      DCMU. In PS II-particles, inactivation is accompanied by a reversible release of
      Ca(2+)-ions (one Ca(2+) released per 200 Chl). In isolated thylakoids, where a
      DeltapH was created by ATP-hydrolysis, both inactivation of oxygen evolution (and
      related fluorescence quenching) by internal acidification and the recovery of
      that inactivation can be suppressed by calcium-channel blockers. In the presence
      of the Ca(2+)-ionophore A23187, recovery of Chl-fluorescence (after relaxation of
      the DeltapH) is stimulated by external Ca(2+) and retarded by EGTA. As shown
      previously (Krieger and Weis 1993), inactivation of oxygen evolution at low pH is
      accompanied by an upward shift of the midpoint redox-potential, Em, of QA. Here,
      we show that in isolated PS II particles the pH-dependent redox-shift (about 160
      mV, as measured from redox titration of Chl-fluorescence) is suppressed by Ca(2+)
      channel blockers and DCMU. When a redox potential of -80 to -120mV was
      established in a suspension of isolated thylakoids, the primary quinone acceptor,
      QA, was largely reduced in presence of a DeltapH (created by ATP-hydrolysis) but
      oxidized in presence of an uncoupler. Ca(2+)-binding at the lumen side seems to
      control redox processes at the lumen- and stroma-side of PS II. We discuss Ca(2+)
      release to be involved in the physiological process of 'high energy quenching'. 

PMID- 24317709
TI  - The relationship between Photosystem II intrinsic quantum yield and millisecond
      luminescence in thylakoids.
AB  - The relationship between charge recombination at Photosystem II (PS II), as
      indicated by millisecond luminescence, and PS II quantum yield was studied in
      spinach thylakoids during electron flow to methylviologen. Under the low
      magnesium conditions used, a decrease in quantum yield was observed in the
      absence of non-photochemical excitation quenching, and therefore cannot be due to
      a restriction in excitation delivery to the reaction centre. It was found that
      the decrease of the parameter Phip, which is a measure of the intrinsic quantum
      yield of 'open' PS II centers, correlates with an increase in luminescence per
      'open' center. The relationship between these two parameters was the same whether
      Phip was manipulated by dissipation of the transthylakoid pH gradient or of the
      electrical potential. This indicates that the mechanism by which Phip decreases
      depends in the same way on the two components of the protonmotive force as does
      the charge recombination at PS II. Calculation of the yield of luminescence with
      respect to the back reaction will be necessary to determine whether the charge
      recombination occurs at a sufficiently high rate to be directly responsible for
      the Phip decrease. 

PMID- 24317710
TI  - Cloning and sequencing of mutantpsbB genes of the cyanobacteriumSynechocystis PCC
      6803.
AB  - Ten strains from a collection of mutants ofSynechocystis 6803 defective in
      Photosystem II (PS II) function were transformed with chromosomal DNA of wild
      type and mutant cells. Cross hybridization data allowed to identify four groups
      of PS II-mutants. Highly efficient transformation was observed between different
      mutant groups, but not within the groups. Restoration of photosynthetic activity
      of the mutant cells was also achieved by transformation with different parts of a
      5.6 kbBam HI fragment of wild typeSynechocystis DNA containing thepsbB gene. Each
      group of mutants was transformed to photoautotrophic growth by specific
      subfragments of thepsbB gene. DNA fragments of four selected mutant strains
      hybridizing with thepsbB gene were isolated and sequenced. The mutations were
      identified as a single nucleotide insertion or substitution leading to stop codon
      formation in two of the mutants, as a deletion of 12 nucleotides, or as a
      nucleotide substitution resulting in an amino acid substitution in the other two
      mutants. Deletion of 12 nucleotides in mutant strain PMB1 and stop codon
      formation in strain NF16 affect membrane-spanning regions of the gene product,
      the CP 47 protein. 

PMID- 24317711
TI  - On the rates of cyclic electron transport around Photosystem II in the presence
      of donor side limitation.
AB  - Photosystem II cyclic electron transport was investigated at low pH in spinach
      thylakoids and PS II preparations from the cyanobacteriumPhormidium laminosum.
      Variable fluorescence (Fv) quenching at a very low light intensity was examined
      as an indicator of cyclic electron flow. A progressive quenching of Fv was
      observed as the pH was lowered; however, this was shown to be mainly due to an
      inhibition of oxygen evolution. Cyclic electron flow in the uninhibited centres
      was estimated to occur at a rate comparable to or smaller than 1 MU mole O2 mg
      Chl(-1) h(-1) in the pH range 5.0 to 7.8.The quantum yeeld of oxygen production
      is known to decrease at low pH and has been taken to indicate cyclic electron
      flow (Crofts and Horton (1991) Biochim Biophys Acta 1058: 187-193). However, a
      direct all-or-none inhibition of oxygen production at low pH has also been
      reported (Meyer et al. (1989) Biochim Biophys Acta 974: 36-43). We have analysed
      the effects of light intensity on the rates of oxygen evolution in order to
      calculate PhiU, the quantum yield of open and uninhibited centres. PhiU was found
      to be constant over a broad pH range, and by using ferricyanide and phenyl-p
      benzoquinone as electron acceptors the maximum possible rate of cyclic electron
      transport was equivalent to no more than 1 MUmole O2 mg Chl(-1) h(-1). The rate
      was no greater when the acceptor was adjusted to provide the most favourable
      conditions for cyclic flow. 

PMID- 24317712
TI  - Periodicity and chaos in a photosynthetic system.
AB  - In this paper experimental results of investigation of the oscillations in a
      photosynthetic system are presented and a model for their interpretation is
      suggested. Periodicities in photosynthetic systems detected in earlier studies by
      physical chemical methods can be also detected by means of recording the
      potential difference between two point electrodes. The observed dependences
      demonstrate a wide range of various types of behaviour of the system, working,
      e.g. in periodic, quasiperiodic, chaotic or 'pulse' regimes. Since the until-now
      used 2-dimensional theoretical model, based on the existence of two dominant
      autocatalytical processes, appeared not to be sufficient for explaining such
      types of the regimes, a generalized 3-dimensional autocatalytical model is
      suggested, which is able to explain all the above mentioned photosynthetic
      regimes. 

PMID- 24317713
TI  - Characterization of the complex interaction between the electron acceptor
      silicomolybdate and Photosystem II.
AB  - Silicomolybdate (SiMo) and its effects on thylakoids have been characterized to
      evaluate its use as a probe for Photosystem II (PS II). It can accept electrons
      at two places in the electron transport chain: one at PS II and the other at PS
      I. In the presence of 1 MUM 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone
      (DBMIB) only the site at PS II is available. It is suggested that SiMo must
      disp;ace bicarbonate from its binding site to be able to function as an electron
      acceptor. This displacement is non-competitive. The binding of SiMo is inhibited
      differentially by PS II inhibitors: dinoseb>ioxynil> diuron. This difference is
      determined by the different positions of the inhibitors within the QB binding
      niche and their interaction with bicarbonate. The experimental results show that
      the SiMo-binding niche is located between the parallel helices of the D1 and D2
      proteins of PS II, close to the non-heme iron. We conclude that SiMo is an
      electron acceptor with unique characteristics useful as a probe of the acceptor
      side of PS II. 

PMID- 24317714
TI  - Manic-depressive illness in adolescence.
AB  - The efficacy of lithium carbonate as a treatment for manic-depressive illness has
      stimulated a reevaluation of the syndrome. In this paper, the authors review the
      obstacles to timely diagnosis of manic-depressive illness in the adolescent.
      Three cases are presented demonstrating the usefulness of a unitary concept in
      which manic-depressive illness is understood and appreciated as having a
      physiologic basis, manifesting its effects in the total body system. The
      heterofore diverse and confusing psychological and behavioral symptoms of manic
      depressive illness in adolescents become intelligible when regarded as secondary
      phenomena: the psychic experience of the process as filtered through the
      psychological constitution of the individual adolescent. 

PMID- 24317715
TI  - A longitudinal study of adolescents' future orientation (time perspective).
AB  - This longitudinal study was designed to test hypotheses concerning the influence
      of environmental changes in different groups (educational status; sex) of
      adolescents on their future orientation (FO). FO was measured through a free
      response questionnaire on which the subjects indicated their hopes and fears
      (which were later categorized into various domains of life by independent
      judges). On a second questionnaire the subjects adjudged their present and future
      life in various given domains of life. The sample consisted of 24 male and 24
      female adolescents, aged between 14-16 years at the time of the first
      measurement; the second measurement took place two years later. Half of the
      subjects of each sex were students at a Gymnasium (preparing for university
      study) at both times of measurement ("high social status"). The other half of the
      subjects of each sex were in their last year at the Hauptschule (continuation of
      elementary education) at the first time of measurement, and had taken up
      employment (e.g., an apprenticeship) by the time of the second measurement ("low
      social status"). At the time of the second measurement relatively more hopes and
      fears were voiced in the domains of personal development and occupation than at
      the first measurement. Independent of time of measurement, low-status subjects
      voiced relatively more hopes and fears related to the occupational domain, and
      boys had a more extended FO than girls. Low-status subjects - as compared to high
      status subjects as well as to their own judgments at the first measurement -
      believed to a greater extent that the materialization of their hopes and fears
      depended on themselves rather than on external forces. These results support the
      assumption that FO cannot be dealt with as a global concept and that FO can be
      modified by change in the external environments, such as entry into an
      occupation. 

PMID- 24317716
TI  - Personality characteristics of black youth: A cross-cultural investigation.
AB  - The view that black youth frequently manifest disordered personalities and
      negative self-concepts is examined through a comparison of the responses of black
      and white female adolescents from differing cultural and social class backgrounds
      to an Adjective Check List. While dissimilar from white female adolescents in
      many important respects, black subjects scored high on indices of personal
      adjustment and did not describe themselves in negatively valued terms. In fact,
      black girls from lower socioeconomic backgrounds, who are generally portrayed as
      particularly prone to pathology and negative self-evaluations, describe
      themselves in more favorable terms than black and white subjects from middle
      class backgrounds. Moreover, U.S. and Jamaican black subjects describe themselves
      in surprisingly similar fashion, and differ in similar respects from their white
      American counterparts, thereby providing some evidence for the impact of a common
      cultural heritage on black personality cross-nationally. 

PMID- 24317717
TI  - The effects of the Yom Kippur War on values of Israeli female students.
AB  - The Rokeach Terminal Value Scale and an attitude questionnaire were administered
      to two similar groups of female Israeli students before and after the Yom Kippur
      War. The second group also responded to a questionnaire about the effects of the
      war on the importance attributed to each of the values. The results were as
      follow: (a) Subjects stated that after the war 14 out of the 18 values in the
      Rokeach list increased in importance. (b) The war brought about a significant
      increase in the relative importance (rank) of 4 values (Pleasure, National
      Security, Happiness, and Mature Love), and a significant decrease in Equality.
      (c) No attitude change was found in respect to issues related to the war itself.
      (d) Values accounted for a smaller percent of the variance in attitudes after the
      war than they did before it. In view of these findings it is suggested that a
      distinction be made between relative and absolute importance within a value
      system. 

PMID- 24317718
TI  - Phenomenological correlates of perceived quality of parenting: A questionnaire
      study of high school students.

PMID- 24317719
TI  - Adolescent women's developing identity: A study of self-definition in the context
      of family relationships.
AB  - This study generated adolescent women's perception of their identity in relation
      to family members spanning three generations and related these perceived
      relationships to their sex-role orientation. Subjects were 20 firstborn
      university women from intact families. The methodology used multiple sources of
      information, including open-ended interviewing procedures, rating scales, and
      standard research measures of sex-role identity. Significantly more constructs
      empirically differentiated family by generation than by sex. Congruence of young
      women with both the parent and grandparent generation, relative number of
      masculine stereotypes produced, and personality traits of males and females were
      significantly influenced by the presence of a brother in the sibling generation.
      There was no relationship between family constellation and sex-role orientation.
      Feminine women were significantly more congruent with other females in their
      family than androgynous women. There was a linear trend for androgynous women to
      be increasingly individuated across the generations. 

PMID- 24317720
TI  - Toward the development of an objective assessment of ego-identity status.
AB  - Four investigations were completed to develop a self-report measure of ego
      identity status. Following James Marcia's definition of diffusion, moratorium,
      foreclosure, and identity achievement status, a series of Likert-type items were
      constructed and validated for use in the study of ego-identity formation.
      Convergent-divergent, concurrent, and predictive validity and test-retest
      reliability are documented in the reported data. Cross-sectional data suggest the
      measure will be sensitive to intraindividual change in identity formation. The
      new Objective Measure of Ego-Identity Status allows researchers to use either a
      "typology" or a "distribution of stage responses" in future longitudinal
      investigations. 

PMID- 24317721
TI  - Developmental changes through adolescence in the spontaneous nomination of
      reference groups as a function of decision content.
AB  - The achievement of behavioral autonomy and psychological independence from the
      family is one of the foremost developmental tasks of the adolescent. This aspect
      of adolescent socialization is examined with regard to the developmental trends
      in the individual's nomination of socialization groups as competent referents in
      different areas of judgment. Eighty subjects, distributed equally between sex and
      among samples drawn from the fifth, seventh, ninth, and twelfth grades, were
      interviewed and allowed to nominate spontaneously reference groups of their own
      choosing for guidance in moral, informational, and social judgments. A
      significant relation was found between the nomination of a particular reference
      group and the nature of the decision to be made. The distribution of reference
      group nominations among the grade levels sampled differed significantly in the
      case of informational and social judgments. With increasing age during
      adolescence, peers seemed to be a more acceptable source of information in
      matters of social judgment than either parents or adults outside the family.
      Adults outside the family, however, exhibited a marked increase in acceptability
      as a reference group for judgments of an informational nature. Parents seemed to
      be the most acceptable referent across all grades for moral judgments. The
      findings are viewed particularly in relation to the results of studies which have
      examined developmental trends in simulated group conformity situations and
      susceptibility to cross-pressures. The possible reasons for the different
      developmental phenomena revealed by this study and by the conformity studies are
      discussed. 

PMID- 24317722
TI  - Is there relation between COL4A1/A2 mutations and antenatally detected fetal
      intraventricular hemorrhage?
AB  - BACKGROUND: The aim of the present study is to evaluate the role of COL4A1/A2
      mutations in the etiology of intraventricular hemorrhage (IVH) detected in-utero.
      METHODS: The data of four cases with fetal IVH were analyzed retrospectively.
      Antenatal risk factors, clinical features, postnatal outcome, and the presence of
      COL4A1/A2 mutations were evaluated. RESULTS: Eight cases of fetal IVH were
      diagnosed between 2005 and 2012 in Erciyes University. Of these, four were
      eligible for genetic analysis. Mean gestational age at diagnosis was 30 weeks 5
      day (min-max: 28-34 weeks); two cases had grade III hemorrhage and two cases had
      grade IV hemorrhage according to fetal magnetic resonance imaging. Three cases
      had severe neurodevelopmental delay and one case had mild deficit. In all cases,
      postnatal evaluation revealed no underlying cause, and no retinal hemorrhagia and
      hematuria were detected. The mean postnatal follow-up was 19 months, and no
      recurrent hemorrhages and porencephalic cyst formation were observed. The whole
      exome sequencing showed no pathological mutations of COL4A1 and COL4A2 in the
      four patients. CONCLUSION: Our data showed that fetal intraventricular hemorrhage
      is not associated with COL4A1 and COL4A2 mutations in the absence of
      porencephaly, recurrent hemorrhage, and other organ bleeding.

PMID- 24317723
TI  - Proposal for a new mediastinal compartment classification of transverse plane
      images according to the Japanese Association for Research on the Thymus (JART)
      General Rules for the Study of Mediastinal Tumors.
AB  - There is no existing worldwide published method for mediastinum compartment
      classification based on transverse section images for the differential diagnosis
      of mediastinal tumors. Herein, we describe a new method for anatomic mediastinal
      compartment classification using transverse section computed tomography (CT)
      images and the use of this method to classify mediastinal lesions, and thus
      evaluate whether the method is sufficiently user-friendly and useful. In a
      publication of the Japanese Association for Research on the Thymus (JART), we
      proposed the following four mediastinal compartments based on transverse CT
      images: superior portion of mediastinum, anterior mediastinum (prevascular zone),
      middle mediastinum (peri-tracheoesophageal zone), and posterior mediastinum
      (paravertebral zone). In the present study, we retrospectively analyzed 445
      pathologically proven mediastinal mass lesions, and categorized them into the
      proposed four compartments by consensus reading. Mass lesions were classified
      into compartments based on the location of the lesion centroid, and each lesion
      was satisfactorily categorized into a compartment. Almost all thymic epithelial
      tumors (99%, 244/246), all 24 thymic malignant lymphomas and a majority of germ
      cell neoplasms (93%, 54/58) were classified as being in the anterior mediastinum
      compartment. The majority of intrathoracic goiters (82%, 14/17) were categorized
      as being in the superior portion of the mediastinum compartment. Approximately
      two-thirds of mass lesions in the middle mediastinum were cysts, including
      foregut and pericardial cysts. Approximately 80% of 37 mass lesions in the
      posterior mediastinum were neurogenic tumors. Correspondingly, 29 of the 49
      neurogenic tumors (60%) were categorized as being in the posterior mediastinum,
      while 10 (20%) were in the superior portion of the mediastinum, 4 (8%) in the
      anterior mediastinum, and 6 (12%) in the middle mediastinum. Our findings showed
      that the newly proposed mediastinal compartment classification using transverse
      images appears to be user-friendly enough for practical clinical application and
      may be helpful in differential diagnoses.

PMID- 24317724
TI  - Anti-HIV-1 activity of Trim 37.
AB  - Trim 5alpha was the first member of the tripartite motif (TRIM) family of
      proteins that was identified to potently restrict human immunodeficiency virus
      type 1 (HIV-1) replication. The breadth of antiretroviral activity of TRIM family
      members is an active area of investigation. In this study, we demonstrate that
      human Trim 37 possesses anti-HIV-1 activity. This antiretroviral activity and the
      manner in which it was displayed were implicated by (1) decreased viral
      replication upon Trim 37 transient overexpression in virus-producing cells, (2)
      correlation of the reduction of viral infectivity with Trim 37 virion
      incorporation, (3) increased HIV-1 replication during siRNA depletion of Trim 37
      expression, and (4) reduction in viral DNA synthesis upon Trim 37 transient
      overexpression. Our findings provide the first demonstration, to our knowledge,
      of the potent antiviral activity of human Trim 37, and implicate an antiviral
      mechanism whereby Trim 37 interferes with viral DNA synthesis. 

PMID- 24317725
TI  - Effect of benzyladenine on the development of plastids and microbodies in excised
      watermelon cotyledons.
AB  - Excised watermelon (Citrullus vulgaris Schrad.) cotyledons were grown in the dark
      in the presence of 0.1 mM benzyladenine (BA). Under these conditions reserve
      breakdown and organelle differentiation progress very slowly. Treatment with BA
      accelerates, breakdown of reserves and stimulates development of organelles.
      Electron micrographs of cells from treated cotyledons show a larger number of
      plastids with a more developed inner membrane system. The levels of plastid
      pigments and enzymes are increased while starch content is reduced. Glyoxysomal
      enzyme levels are increased by BA during the first three days of development and
      their decline is accelerated thereafter. Also the activity of hydroxypyruvate
      reductase (EC 1.1.1.81.), a peroxisomal enzyme, is increased, but this increase
      is not followed by a decay phase. In water controls, hydroxypyruvate reductase
      bands together with glyoxysomal enzymes after equilibrium centrifugation in a
      sucrose gradient. In treated cotyledons the equilibrium position of glyoxysomal
      enzymes is uchanged while that of hydroxypyruvate reductase is shifted to a lower
      density. 

PMID- 24317726
TI  - Effect of carbon dioxide and temperature on photosynthetic CO2 uptake and
      photorespiratory CO 2 evolution in sunflower leaves.
AB  - Using an open gas-exchange system, apparent photosynthesis, true photosynthesis
      (TPS), photorespiration (PR) and dark respiration of sunflower (Helianthus annuus
      L.) leaves were determined at three temperatures and between 50 and 400 MUl/l
      external CO2. The ratio of PR/TPS and the solubility ratio of O2/CO2 in the
      intercellular spaces both decreased with increasing CO2. The rate of PR was not
      affected by the CO2 concentration in the leaves and was independent of the
      solubility ratio of oxygen and CO2 in the leaf cell. At photosynthesis-limiting
      concentrations of CO2, the ratio of PR/TPS significantly increased from 18 to 30
      degrees C and the rate of PR increased from 4.3 mg CO2 dm(-2) h(-1) at 18 degrees
      C to 8.6 mg CO2 dm(-2) h(-1) at 30 degrees C. The specific activity of
      photorespired CO2 was CO2-dependent but temperature-independent, and the carbon
      traversing the glycolate pathway appeared to be derived both from recently fixed
      assimilate and from older reserve materials. It is concluded that PR as a
      percentage of TPS is affected by the concentrations of O2 and CO2 around the
      photosynthesizing cells, but the rate of PR may also be controlled by other
      factors. 

PMID- 24317727
TI  - Calcium ionophore A 23187 affects localized wall secretion in the tip region of
      pollen tubes of Lilium longiflorum.
AB  - The effects of the calcium inonophore A 23187 on growing pollen tubes of Lilium
      longiflorum Thunb. cv. Ace were investigated with the light and electron
      microscope. Tip growth is slowed down and stopped within 20 min after application
      of 5x10(-5) M ionophore A 23187. The main effects are the disappearance of the
      clear zone at the pollen tube tip and a thickening of the cell wall at the tip
      and at the pollen tube flanks. This effect on cell wall formation is confirmed
      under the electron microscope: The vesicular zone in treated pollen tubes is
      reduced, numerous vesicular contents are irregularly integrated in the pollen
      tube wall not only in the tip, but over a long distance of the pollen tube wall.
      In addition, effects on mitochondria and dictyosomes are observed. These results
      are interpreted as a disorientation of the Ca(2+)-based orientation mechanism of
      exocytosis after equilibration of the Ca(2+)-gradient. 

PMID- 24317728
TI  - Gibberellic-acid-promoted transport of assimilates in stems of Phaseolus vulgaris
      L. : Localized versus remote site(s) of action.
AB  - Gibberellic acid (GA3), applied as a dispersion in aqueous lanolin to the stumps
      of decapitated stems of P. vulgaris plants, was found to promote the transfer of
      (14)C-and (32)P-labelled assimilates to the site of hormone application.
      Measurements of the component transfer processes, operating between source and
      sink (site of hormone application), showed that GA3 was not acting to promote
      assimilate transfer by increasing the photosynthetic rate of, or the assimilate
      export rate from the source, nor by altering the mobilizing ability of the
      competing root sink. Here, it also was found that the time between GA3
      application and detection of an enhanced transport flux was independent of the
      length of the transport pathway. Overall, the evidence obtained indicated that
      GA3 was not acting on any transfer process remote from its point of hormone
      application but was acting locally at this latter point. 

PMID- 24317729
TI  - Effect of stereospecific hydroxylation of N(6)-(Delta (2)-Isopentenyl)adenosine
      on cytokinin activity.
AB  - The cytokinin activities of cis and trans ribosylzeatin isomers and that of N(6)
      (Delta(2)-isopentenyl)adenosine were compared in four bioassays. The trans isomer
      was found to be more active than the cis isomer in stimulation of cucumber
      cotyledon expansion (100x), retention of chlorophyll in detached leaf pieces
      (7x), induction and stimulation of chlorophyll synthesis in cucumber cotyledons
      (20x) and of betacyanin synthesis in Amaranthus caudatus seedlings grown in the
      dark (60x). The N(6)-(Delta(2)-isopentenyl)adenosine adenosine was less active
      than the trans ribosylzeatin in all four bioassays and more active than the cis
      ribosylzeatin in induction and stimulation of betacyanin and chlorophyll
      synthesis. These results show that the hydroxylation of the trans methyl group in
      the N(6) side chain of N(6)-(Delta(2)-isopentenyl)adenosine increases the
      biological activity and that this activity is either decreased or not
      significantly changed when the cis methyl group is hydroxylated. 

PMID- 24317730
TI  - Identical embryonal proteins in intact and isolated tissues of maize (Zea mays
      L.).
AB  - Minor antigens characteristic of developing and mature embryos were not found in
      the shoot and root meristems of the seedlings. Some of these embryonal antigens
      (EA) were present, however, in callus and cell-suspension cultures, irrespective
      of their tissue origin, and were maintained throughout repeated subcultures, in
      some cases for more than 2 years. These EA were distinct both from the
      meristematic antigens found in the intact seedlings and in callus cultures, and
      from organ-specific antigens found only in intact plants. The EA of callus
      tissues derived from several maize genotypes were serologically identical. We
      therefore assume that these EA are "proliferation proteins" or "early proteins"
      expressed by cells that have not undergone any determination and lack any tissue
      or organ specificity. 

PMID- 24317731
TI  - A systematic relationship between phytochrome-controlled development and species
      habitat, for plants grown in simulated natural radiation.
AB  - A survey of the responsiveness of plant species, typical of open and shade
      habitats, to simulated natural shade-light quality (i.e. white light plus
      supplementary far-red) has demonstrated a systematic relationship between habitat
      and certain developmental responses. Supplementary far-red light has a much
      greater effect on stem extension rate, petiole length, and leaf dry weight: stem
      dry weight ratio of the open habitat, shade-intolerant species. Far-red effects
      on leaf chlorophyll content show no such systematic grading. These results are
      discussed in relation to habitat adaptation. In most cases, the relationship
      between developmental response and the estimated phytochrome photoequilibrium,
      which is established by the radiation treatment, is linear. This is taken as an
      indication of phytochrome involvement in shade perception. 

PMID- 24317732
TI  - Analysis and characterization of DCMU-resistant Euglena gracilis : III. Thylakoid
      modifications and dark "recovery" of photosynthesis.
AB  - Dark-grown, DCMU-adapted Euglena gracilis Z (ZR) are able to undergo light
      induced chloroplast development in the presence or absence of DCMU. The
      differentiated chloroplasts are photosynthetically active and are resistant not
      only to DCMU, but also to an analog, o-phenanthrolene. When DCMU overdoses are
      added to ZR cells or to chloroplasts isolated from these cells, photosynthesis is
      partially inhibited. A brief period of darkness removes this inhibition. This
      recovery phenomenon is related to DCMU resistance, since it is not exhibited by
      non-resistant control cells. The chloroplast protein synthesis apparatus is not
      involved in DCMU resistance. Rather, this phenomenon is apparently related to new
      characteristics of thylakoids. It is shown that photosynthetic recovery by ZR
      cells depends on the accessibility and fluid properties of membranes. The
      analysis of fluorescence induction kinetics shows that changes in the
      environmental conformation of photosystem II units occur during recovery. 

PMID- 24317733
TI  - Floral initiation in sorghum hastened by gibberellic acid and far-red light.
AB  - Combinations of far-red light (FR) (4 min) and gibberellic acid (GA3), given at
      the beginning of a daily 12-h dark period in a growth room, were used to study
      floral induction in four maturity genotypes of the milo group of sorghum (Sorghum
      bicolor (L.) Moench). The 12-h dark period without GA3 application or FR induced
      flowering in only the early genotype; FR hastened initiation in the early
      genotype, while GA3 hastened floral initiation in the two intermidiate-flowering
      genotypes. GA3 and FR together had a strong synergistic effect, hastening floral
      initiation by 30 to more than 80 d in the early and intermediate genotypes. Red
      light (R) did not hasten flowering; FR preceded by R gave the same effect as FR
      alone. GA3 promoted stem elongation equally whether floral initiation occurred or
      not; thus, its effect on stem elongation was independent of floral initiation.
      The capacity of GA3 to induce flowering in sorghum, a short-day plant, seems to
      be enhanced by phytochrome being in the PR form at the beginning of the night
      when GA3 was applied. 

PMID- 24317734
TI  - Cell suspensions for kinetic studies of inhibitor action : The rapid initial
      action of dikegulac on membrane properties in situ.
AB  - Because of uniformity and small distances for transport, cell suspensions offer a
      system for rapid measurements of initial reactions of phytotoxic compounds. We
      had previously shown that a growth regulator, dikegulac (2,3:4,6 di-o
      isopropylidine-2-keto-L-gulonate) inhibits amino acid incorporation into
      proteins. Using Solanum nigrum suspension cultures, it was found that dikegulac
      rapidly inhibits amino acid uptake into cells, before inhibiting incorporation,
      with time points starting at a few minutes, and kinetics that can be extrapolated
      back to time zero. With more rapid kinetics this compound induces leakage of a
      preloaded dye. The rate of leakage was less with stationary cells in suspension,
      reiterating that they are more resistant to the effects of this compound. It was
      thus concluded that at the concentrations used, the first effect of dikegulac (or
      one very close to the first effect) is on the cell membrane. 

PMID- 24317735
TI  - Changes in protein synthesis during the initial stage of life of tobacco
      protoplasts.
AB  - The biosynthesis of Fraction I protein in isolated protoplasts is compared with
      that in the plant. Radioactive precursors were incorporated into isolated
      protoplasts ("in vitro" labeling) and into leaves, from which the protoplasts
      were isolated later ("in situ" labeling). The biosynthesis of Fraction I protein
      stopped almost completely as soon as the protoplasts were incubated in the
      culture medium. 

PMID- 24317736
TI  - Intracellular interactions between the pathways of carbohydrate oxidation and
      nitrate assimilation in plant roots.
AB  - Using density gradient techniques we have shown that in addition to a location
      within the cytoplasm all the enzymes of the pentose phosphate pathway are also
      present within the plastids of apical cells of pea roots. The data are discussed
      in relation to the hypothesis that the pentose phosphate pathway provides the
      NADPH for nitrite assimilation, the enzymes of which pathway have previously been
      shown to be located within the plastids of apical cells of pea roots. 

PMID- 24317737
TI  - Assay for and enzymatic formation of an ethylene precursor, 1-aminocyclopropane-1
      carboxylic acid.
AB  - A simple and sensitive chemical assay was developed for 1-aminocyclopropane-1
      carboxylic acid (ACC), a precursor of ethylene. The assay is based on the
      liberation of ethylene from ACC at pH 11.5 in the presence of pyridoxal
      phosphate, MnCl2 and H2O2. This assay was used to detect ACC in extracts of
      tomato fruits (Lycopersicon esculentum Mill.) and to measure the activity of a
      soluble enzyme from tomato fruit that converted S-adenosylmethionine (SAM) to
      ACC. The enzyme had a Km of 13 MUM for SAM, and conversion of SAM to ACC was
      competitively and reversibly inhibited by aminoethoxyvinylglycine (AVG), an
      analog of rhizobitoxine. The Ki value for AVG was 0.2 MUM. The level of the ACC
      forming enzyme activity was positively correlated with the content of ACC and the
      rate of ethylene formation in wild-type tomatoes of different developmental
      stages. Mature fruits of the rin (non-ripening) mutant of tomato, which only
      produce low levels of ethylene, contained much lower levels of ACC and of the ACC
      forming enzyme activity than wild-type tomato fruits of comparable age. 

PMID- 24317738
TI  - Somatic embryogenesis in suspension cultures of Gossypium klotzschianum anderss.
AB  - Somatic embryoids differentiated in suspension cultures of G. klotzschianum after
      3-4 weeks of culture in a liquid medium containing glutamine (optimally, 10-15
      mM). Embryogenesis occurred after a preculture of callus on a medium containing
      10 mg/l of the cytokinin, 2iP. The embryoids had meristematic regions, a well
      formed epidermis, and formed roots and vestigial leaves. Asparagine was much less
      effective than glutamine in promoting embryoid differentiation. The presence of
      2,4-D in the medium resulted in increased vigor of the suspension cultures and
      subsequently in the formation of many embryoids, but does not seem to be
      necessary for somatic embryogenesis in cotton. 

PMID- 24317740
TI  - Fragmentation dynamics of the ethyl bromide and ethyl iodide cations: a velocity
      map imaging study.
AB  - The photodissociation dynamics of ethyl bromide and ethyl iodide cations
      (C2H5Br(+) and C2H5I(+)) have been studied. Ethyl halide cations were formed
      through vacuum ultraviolet (VUV) photoionization of the respective neutral parent
      molecules at 118.2 nm, and were photolysed at a number of ultraviolet (UV)
      photolysis wavelengths, including 355 nm and wavelengths in the range from 236 to
      266 nm. Time-of-flight mass spectra and velocity-map images have been acquired
      for all fragment ions and for ground (Br) and spin-orbit excited (Br*) bromine
      atom products, allowing multiple fragmentation pathways to be investigated. The
      experimental studies are complemented by spin-orbit resolved ab initio
      calculations of cuts through the potential energy surfaces (along the RC-Br/I
      stretch coordinate) for the ground and first few excited states of the respective
      cations. Analysis of the velocity-map images indicates that photoexcited
      C2H5Br(+) cations undergo prompt C-Br bond fission to form predominantly C2H5(+)
      + Br* products with a near-limiting 'parallel' recoil velocity distribution. The
      observed C2H3(+) + H2 + Br product channel is thought to arise via unimolecular
      decay of highly internally excited C2H5(+) products formed following
      radiationless transfer from the initial excited state populated by photon
      absorption. Broadly similar behaviour is observed in the case of C2H5I(+), along
      with an additional energetically accessible C-I bond fission channel to form C2H5
      + I(+) products. HX (X = Br, I) elimination from the highly internally excited
      C2H5X(+) cation is deemed the most probable route to forming the C2H4(+) fragment
      ions observed from both cations. Finally, both ethyl halide cations also show
      evidence of a minor C-C bond fission process to form CH2X(+) + CH3 products. 

PMID- 24317739
TI  - Cells of origin of squamous epithelium, dysplasia and cancer in the head and neck
      region after bone marrow transplantation.
AB  - Secondary solid tumors that occur after hematopoietic stem cell transplantation
      (HSCT) are late complications of HSCT. Previously, secondary solid tumors were
      considered to be recipient-derived cells because transplanted cells do not
      contain epithelial cells. Recently, however, not only donor-derived epithelial
      cells but also donor-derived secondary solid tumors have also been reported in
      mice and humans. It means that circulating bone marrow-derived stem cells (BMDCs)
      including hematopoietic stem cells include the stem cells of many tissue types
      and the precancerous cells of many solid tumors. In most reports of donor-derived
      secondary solid tumors, however, tumors contained a low proportion of BMDC
      derived epithelial cells in mixed solid tumor tissues. To our knowledge, there
      are only five known cases of completely donor-derived tumor tissues, i.e., four
      oral SCCs and a pharyngeal SCC. In this study, we analyzed five human clinical
      samples of solid tumors, i.e., two esophageal squamous cell carcinomas (SCCs),
      two oral SCCs and a tongue carcinoma. In the oral and tongue, completely donor
      derived tissues were not observed, but in esophagus a completely donor-derived
      esophageal epidermis and SCC were observed for the first time. In addition, in
      another esophageal SCC patient, a completely donor-derived dysplasia region of
      esophageal epidermis was observed near recipient-derived SCC. This study suggests
      that BMDC-derived cells include the stem cells of esophageal epidermis and the
      precancerous cells of esophageal SCC and can differentiate into esophageal
      epithelium and esophageal SCC. 

PMID- 24317741
TI  - Variation in (18)F-FDG PET findings in a patient with synchronous multiple
      thymoma.
AB  - We herein present a case of synchronous multiple thymoma that was suspected based
      on the findings of positron emission tomography with fluorine-18-labeled
      fluorodeoxyglucose ((18)F-FDG PET). The patient was a 70-year-old male with two
      similarly sized and heterogeneously enhanced masses on the right side of the
      anterior mediastinum on chest computed tomography. (18)F-FDG PET revealed
      variation in FDG accumulation between the masses, in which the maximum
      standardized uptake value was 4.4 in Tumor 1 and 8.7 in Tumor 2. Based on these
      imaging findings, the masses were suspected to be independent, likely synchronous
      double primary thymoma. Total thymectomy with removal of the two tumors was
      performed via median sternotomy. A pathological examination identified Tumor 1 as
      type AB thymoma and Tumor 2 as type A thymoma. This is the first reported case of
      synchronous multiple thymoma which was suspected based on a variation in the
      (18)F-FDG PET findings between the tumors. 

PMID- 24317742
TI  - A cardiac hemangioma treated by a right minithoracotomy approach with
      thoracoscopic assistance.
AB  - Cardiac hemangiomas are extremely rare tumors, accounting for only 2.5% of all
      cardiac tumors. Most of these develop in the ventricles, and obtaining a good
      field of view is, therefore, the key to successful operation. A 40-year-old
      female visited a local hospital due to palpitation. Transthoracic
      echocardiography revealed a spherical high-echo mass (13.5 * 10.7 mm in diameter)
      between the papillary muscles. She was referred to our hospital to undergo close
      examination. Cardiac contrast-enhanced magnetic resonance imaging was performed
      to differentiate between malignant and benign lesions. However, this did not
      provide any findings leading to a definite diagnosis. To make a diagnosis and
      prevent embolism, the mass was excised using a right minithoracotomy approach
      with thoracoscopic assistance. The post-operative pathological diagnosis was a
      cardiac capillary-cavernous hemangioma. A right minithoracotomy approach combined
      with thoracoscopy allowed accurate evaluation of the mass in the left ventricle
      beyond the mitral valve and its accurate excision.

PMID- 24317743
TI  - Comparative studies of how living circumstances influence medication adherence in
      >=65 year olds.
AB  - BACKGROUND: Resources to help the older aged (>=65 year olds) manage their
      medicines should probably target those in greatest need. The older-aged have many
      different types of living circumstances. There are different locations (urban,
      rural), different types of housing (in the community or in retirement villages),
      different living arrangements (living alone or with others), and different
      socioeconomic status (SES) circumstances. However, there has been limited
      attention to whether these living circumstances affect adherence to medicines in
      the >=65 year olds. AIM OF THE REVIEW: The aim was to determine whether
      comparative studies, including logistic regression studies, show that living
      circumstances affect adherence to medicines by the >=65 year olds. METHODS: A
      literature search of Medline, CINAHL and the Internet (Google) was undertaken.
      RESULTS: Four comparative studies have not shown differences in adherence to
      medicines between the >=65 year olds living in rural and urban locations, but one
      study shows lower adherence to medicines for osteoporosis in rural areas compared
      to metropolitan, and another study shows greater adherence to antihypertensive
      medicines in rural than urban areas. There are no comparative studies of
      adherence to medicines in the older-aged living in indigenous communities
      compared to other communities. There is conflicting evidence as to whether living
      alone, being unmarried, or having a low income/worth is associated with
      nonadherence. Preliminary studies have suggested that the older-aged living in
      rental, low SES retirement villages or leasehold, middle SES retirement villages
      have a lower adherence to medicines than those living in freehold, high SES
      retirement villages. CONCLUSIONS: The >=65 year olds living in rural communities
      may need extra help with adherence to medicines for osteoporosis. The >=65 year
      olds living in rental or leasehold retirement villages may require extra
      assistance/resources to adhere to their medicines. Further research is needed to
      clarify whether living under certain living circumstances (e.g. living alone,
      being unmarried, low income) has an effect on adherence, and to determine whether
      the >=65 year olds living in indigenous communities need assistance to be
      adherent to prescribed medicines.

PMID- 24317744
TI  - Linear differentiation of cereal chromosomes : I. Common wheat and its supposed
      ancestors.
AB  - Using the Giemsa technique of differential staining (the BSG test), we have
      studies the karyotypes and constructed the idiograms of T. aestivum L. var.
      'Diamant' and 'Chinese Spring', T. Monococcum L. v. 'hornemannii' ssp. roles
      occidentali georgicum Dek., Aegilops squarrosa L. v. 'Meeyeri', T. aestivum. The
      karyotypes of 'Chinese Spring' and 'Diamant' differ drastically both in total
      structural heterochromatin content and its localization on the nine
      morphologically homeologous chromosomes. The rest of the twelve pairs of
      chromosomes showed no morphological similarity. This indicates considerable
      differences in the phylogeny of the varieties, and also an absence of unique
      karyotype in T. aestivum.Three chromosomes of Ae. Squarrosa are similar to those
      of 'Chinese Spring', yet, on the whole, the chromosomal structural specificity of
      the diploids studied is so high that we fail to understand the nature of the
      homology between common wheat and its supposed diploid ancestors.The role of
      introgression in the evolution of the genomes of Triticum and Aegilops, and also
      the meaning of the conjugation and BSG tests in resolving the phylogeny, is
      discussed. 

PMID- 24317745
TI  - Laboratory evalution of a translocation double heterozygote for genetic control
      of Aedes aegypti.
AB  - Two pure translocation homozygote stocks, T1/T1 and T3/T3, were used to produce a
      double translocation heterozygote system designated T1/T3, employing T1/T1 as the
      male and T3/T3 as the female parent. The double heterozygote showed 73 %
      sterility when mated to wild females. Tests on mating competitiveness,
      recombination frequency in the differential segment, insemination rate and
      inheritance of sterility after release, for four generations in laboratory cages,
      have been carried out to evaluate the efficiency of this strain as an agent for a
      population control programme. 

PMID- 24317746
TI  - A case of genome partition in polyploid oats.
AB  - At the second generation of the interspecific cross between the cultivated
      hexaploid (2n = 42) oat A. Sativa and the wild tetraploid (2n = 28) A. Murphyi, a
      plant having hexaploid and diploid (2n = 14) sectors was selected. Meiosis was
      highly regular in the diploid sector but the tillers failed to proceed beyond the
      boot stage and no seeds were produced. It is suggested that this diploid sector
      represents an entire genome of one of the diploid progenitors of the hexaploid
      oat. 

PMID- 24317747
TI  - Conditions for a high plating efficiency of free cell suspensions of Haplopappus
      gracilis (Nutt) gray.
AB  - Suspensions of Haplopappus gracilis cells, containing about 80% free cells, were
      obt ained from log-phase cultures by filtration through 3 nylon sieves having
      decreasing mesh widths from 297, 210 and 88 MUm. From the free cell suspensions,
      75 to 90% of the cells developed into visible colonies when the plating procedure
      was divided into two steps: a) plating the cells at high concentration in soft
      agar on feeder agar; b) replating the resulting aggregations at appropriate
      concentrations on fresh feeder agar. From the results, it is inferred that, in
      the replating step, the volume of the inoculum is the deciding factor which
      influences the resulting plating efficiency. 

PMID- 24317748
TI  - Effect of gibberellic acid treatment, and nutrient supply through detached
      tillers, upon haploid frequency in barley.
AB  - Haploids from Hordeum vulgare (2n = 14) X H. Bulbosum (2n = 14) crosses result
      after fertilization from the subsequent elimination of bulbosum chromosomes
      during early embryo development. Seed set from the cross is high but embryo
      culture is necessary to obtain seedlings. Application of gibberellin A3 (GA3) to
      pollinated florets was effective for increasing the frequency of haploid
      seedlings produced on both nutrient-fed detached tillers and intact plants. GA3
      increased both seed set and embryo yield. The number of cells per embryo during
      its transition to the haploid state was increased two to three times following
      GA3 treatments. Enhanced embryo and endosperm development was attributed to
      increased mitotic activity. The number of visibly differentiated embryos was
      doubled to about 35 % of the cultured embryos after GA3 was applied to detached
      tillers in nutrient solution. About 70 % of the resulting haploid plants
      developed from the visibly differentiated embryos. The detached tiller technique
      offers a convenient method of culturing haploids from field-grown plants. 

PMID- 24317749
TI  - Multiline varieties and disease control : I. The "dirty crop" approach with each
      component carrying a unique single resistance gene.
AB  - The effects of the widespread use of "dirty crop" or "partially resistant"
      multilines on the racial composition of a pathogen population were investigated
      using simple theoretical models. It was found that the evolutionary changes in
      the pathogen attacking multiline varieties depend critically on two factors - the
      level of selection against unnecessary genes for virulence(s) and the number of
      lines in the multiline (n): (i) If s>0.5, then multilines will stabilize the
      racial composition of the pathogen population and simple races, carrying a single
      gene for virulence, will be the predominant biotypes. (ii) If s< 1/2 (n - 1) when
      unnecessary genes for virulence are additive in their effects in reducing
      pathogen fitness, or s< 1/n when unnecessary virulence genes act multiplicatively
      to reduce pathogen fitness, then the use of a multiline will lead to the
      development of a superrace which can simultaneously attack all the component
      lines. (iii) If 1/2> s>1/2 (n-1) for the additive model, or 1/2> s>1/n for the
      multiplicative model, the use of multiline varieties will stabilize the pathogen
      population, but with complex races, carrying two or more virulence genes,
      predominant. These findings are discussed in relation to the potential of
      multiline varieties as a means of achieving stable, long-term control of plant
      diseases. It is concluded that "dirty crop" and "partially resistant" multilines
      will provide stable disease control in crop plants only in limited and relatively
      rare circumstances. 

PMID- 24317750
TI  - Ivory: a recessive white-eyed tryptophan metabolism mutant with intermediate F2 -
      and R 1 - progenies in the flesh fly Sarcophaga barbata.
AB  - The recessive autosomal gene ivory (i) causes white eyes in the flesh fly
      Sarcophaga barbata. The mutation completely blocks the synthesis of
      formylkynurenine. Ivory larvae and ivory imagoes are able to synthesize
      xanthommatin if formylkynurenine and kynurenine respectively are provided with
      the food. The eye colour of the F2- and the R1-mutants respectively is
      intermediate because these animals have taken up xanthommatin precursors that
      were excreted by the wild-type larvae. The white eye colour is not influenced by
      temperature. The viability of the ivory stock is somewhat lower than that of the
      wild-type stock. The mutation ivory is homologous to the mutation vermilion of
      Drosophila melanogaster and to the mutation green of Musca domestica
      respectively. 

PMID- 24317751
TI  - Epistatic contributions to quantitative traits in Tribolium castaneum : I. Traits
      not closely related to fitness.
AB  - Triple-testcross experiments were used to analyze epistatic contributions to
      larva weight, pupa weight, pupa width and adult weight in Tribolium castaneum.
      Seven diverse inbred lines and the F1. produced by crossing the two tester lines
      were examined for indications of epistasis. Larva weight was the only trait for
      which no significant epistasis was detected. There was significant epistasis for
      pupa weight in three of the inbred lines; for pupa width in four of the inbred
      lines; for adult weight in five of the inbred lines. Only one inbred line and the
      F1 line failed to exhibit significant epistasis for any trait. Each inbred line
      had a unique pattern of epistasis, suggesting that a number of different loci
      were contributing to the detected epistasis. 

PMID- 24317752
TI  - Radioactive pollution and accumulation of radionuclides in wild plants in
      Fukushima.
AB  - The radionuclide status of wild plants and soil in the Fukushima area was
      investigated during the period May 2011 to October 2012, using an imaging plate
      (autoradiograms) or a high purity germanium detector. Analyses of autoradiograms
      showed that wild plants grown in March 2011 were strongly polluted with fallout
      released from the Fukushima 1 Nuclear Power Plant. The radioactivity was mostly
      due to fallout adsorbed on the surface of the plants. On the other hand, a number
      of herbaceous plants were regularly collected in the Fukushima area and their
      radionuclide concentrations were measured with a high-purity germanium detector.
      Plants grown in March 2011 showed very high levels of 134Cs and 137Cs, but these
      radioactivity levels decreased rapidly after July 2011 and eventually became
      lower than that of endogenous 40K. During this period, the radioactivity of the
      soil remained high. We therefore suppose that a significant proportion of the
      radioactivity detected from plants harvested after July 2011 was most likely
      derived from soil dust attached on the plant surface. Autoradiograms of rice
      plants were virtually identical between plants cultivated in Fukushima and Osaka
      area, reflecting the background radiation due to 40K.

PMID- 24317753
TI  - A specialized new species of Ashicaulis (Osmundaceae, Filicales) from the
      Jurassic of Liaoning, NE China.
AB  - A new species of structurally preserved fern rhizome, Ashicaulis plumites
      (Osmundaceae, Filicales), is described from the Middle Jurassic Tiaojishan
      Formation in western Liaoning Province, NE China. The new species is
      characterized by a peculiar sclerenchyma mass in the petiolar vascular bundle
      concavity. This sclerenchyma mass varies from a linear-shape to a mushroom-like
      shape with a remarkable outward protuberance, which distinguishes the present new
      species from other Ashicaulis species. Such a protuberance is very rare among
      osmundaceous ferns, and should represent a unique type for sclerenchymatous
      tissue in the osmundaceous vascular bundle concavity. Recognition of the peculiar
      structure of this new fossil species enriches anatomical diversity of
      permineralized osmundaceous ferns, indicating that the family Osmundaceae might
      have experienced a remarkable diversification during the Middle Jurassic in NE
      China. The new species show anatomical similarities to Osmunda pluma Miller from
      the Palaeocene of North America. The occurrence of A. plumites in the Middle
      Jurassic of China provides a new clue for understanding the evolution of some
      members of the living subgenus Osmunda. 

PMID- 24317754
TI  - Volume changes of extremely large and giant intracranial aneurysms after
      treatment with flow diverter stents.
AB  - INTRODUCTION: This study assessed volume changes of unruptured large and giant
      aneurysms (greatest diameter >20 mm) after treatment with flow diverter (FD)
      stents. METHODS: Clinical audit of the cases treated in a single institution,
      over a 5-year period. Demographic and clinical data were retrospectively
      collected from the hospital records. Aneurysm volumes were measured by manual
      outlining at sequential slices using computerised tomography (CT) or magnetic
      resonance (MR) angiography data. RESULTS: The audit included eight patients
      (seven females) with eight aneurysms. Four aneurysms involved the cavernous
      segment of the internal carotid artery (ICA), three the supraclinoid ICA and one
      the basilar artery. Seven patients presented with signs and symptoms of mass
      effect and one with seizures. All but one aneurysm was treated with a single FD
      stent; six aneurysms were also coiled (either before or simultaneously with FD
      placement). Minimum follow-up time was 6 months (mean 20 months). At follow-up,
      three aneurysms decreased in size, three were unchanged and two increased. Both
      aneurysms that increased in size showed persistent endosaccular flow at follow-up
      MR; in one case, failure was attributed to suboptimal position of the stent; in
      the other case, it was attributed to persistence of a side branch originating
      from the aneurysm (similar to the endoleak phenomenon of aortic aneurysms). At
      follow-up, five aneurysms were completely occluded; none of these increased in
      volume. CONCLUSION: Complete occlusion of the aneurysms leads, in most cases, to
      its shrinkage. In cases of late aneurysm growth or regrowth, consideration should
      be given to possible endoleak as the cause.

PMID- 24317755
TI  - "Stand up straight": notes toward a history of posture.
AB  - The essay presents a set of interlinked claims about posture in modern culture.
      Over the past two centuries it has come to define a wide range of assumptions in
      the West from what makes human beings human (from Lamarck to Darwin and beyond)
      to the efficacy of the body in warfare (from Dutch drill manuals in the 17th
      century to German military medical studies of soldiers in the 19th century).
      Dance and sport both are forms of posture training in terms of their own claims.
      Posture separates 'primitive' from 'advanced' peoples and the 'ill' from the
      'healthy.' Indeed an entire medical sub-specialty developed in which gymnastics
      defined and recuperated the body. But all of these claims were also part of a
      Western attempt to use posture (and the means of altering it) as the litmus test
      for the healthy modern body of the perfect citizen. Focusing on the centrality of
      posture in two oddly linked moments of modern thought--modern Zionist thought and
      Nationalism in early 20th century China--in terms of bodily reform, we show how
      "posture" brings all of the earlier debates together to reform the body.

PMID- 24317756
TI  - Studies on lysine analogs, aspartate-derived amino acids, and attempted mutant
      selection on oat seedlings.
AB  - The lysine analogs S-2-aminoethyl-L-cysteine (AEC) and DL-Delta-hydroxylysine
      (DHL) caused severe growth inhibition in dark-grown oat seedlings (Avena sativa
      L. and A. nuda L.) at similar concentrations while L-lysine methyl ester (LME)
      had little effect. Lysine, arginine, and ornithine reversed the inhibition caused
      by AEC and DHL, the order of effectiveness being lysine>arginine>ornithine. Of
      aspartate-pathway amino acids, tested individually and in combinations for
      inhibitory effects on seedling growth, lysine and combinations containing lysine
      were the most inhibitory, but the inhibition was much less than that produced by
      AEC. Only slight synergistic effects occurred when oat seedlings were grown in
      the presence of paired combinations of aspartatepathway endproduct amino
      acids.Ca. 54,000 seeds obtained from 3,463 plants grown from ethyl
      methanesulfonate (EMS) treated seed were screened for resistance to AEC. Three
      resistant variants were identified but the resistance was not recovered among
      their self-pollinated progeny. 

PMID- 24317757
TI  - Cytokinin biosynthesis in roots of corn.
AB  - Removal of the quiescent center (QC) from the root apex of maize (Zea mays L.,
      cv. Kelvedon 33) initiates a set of events which culiminate in the regeneration
      of an intact apex with a newly formed QC. Concomitant with the formation of a new
      QC is a marked reduction in extractable cytokinins in the tissue of the proximal
      meristem. Replacing the excised QC with a Dowex (acidic cation-exchange resin)
      bead affects both root growth and QC regeneration. Root growth is inhibited by
      "plain" Dowex beads and Dowex beads treated with zeatin; this inhibition is
      reversed if the beads have been treated with CaCl2 (+/-zeatin). Dowex beads
      treated with zeatin delay the formation of a new QC; this effect is the same
      whether or not the beads also contain CaCl2. The results of this investigation
      support the notions that cytokinin biosynthesis in roots is a result of
      activities of both the QC and the proximal meristem, and that cytokinins, at
      least if supplied exogenously, can play a role in root morphogenesis by delaying
      the regeneration of the QC. 

PMID- 24317758
TI  - Distribution of growth regulators in relation to the light-induced geotropic
      responsiveness in Zea roots.
AB  - Growth regulators were measured in extracts from the upper and lower halves of 7
      mm apical segments of horizontally oriented, red-light-irradiated and non
      irradiated roots of Zea mays L. cv. Golden Cross Bantam 70 which exhibit a
      georesponse only after an exposure to light. Abscisic acid (ABA) was measured by
      gas-liquid chromatography, auxin (indole-3-acetic acid, IAA) by the Avena
      straight-growth assay, and an unidentified growth inhibitor by a Zea root-growth
      assay. The ratio of ABA in the upper and lower halves was 1.6 in the irradiated
      roots and 1.0 in the non-irradiated ones. The total amount of ABA after
      irradiation was increased by a factor of ca. 1.8. The ratio of IAA in the upper
      and lower halves of irradiated and non-irradiated roots was 1:3.4 and 1:2.9,
      respectively. The content (or activity) of an unidentified growth inhibitor was
      highest in the lower halves of horizontally oriented roots which had been
      irradiated with red light. The unidentified growth inhibitor, rather than IAA or
      ABA, may be the major factor in the light-induced geotropic responsiveness in Zea
      roots. 

PMID- 24317759
TI  - A close temporal and spatial correlation between cell growth, cell wall synthesis
      and the activity of enzymes of mannan synthesis in Acetabularia mediterranea.
AB  - The synthesis of cell wall mannan and the activities of guanosine-diphosphate
      mannose-pyrophosphorylase (EC2.7.7.13) and mannan synthetase were studied during
      the development of nucleate and enucleated cells of the alga Acetabularia
      mediterranea. The activities of both enzymes are relatively high as long as the
      cells grow and synthesize mannans. With termination of growth and mannan
      synthesis, the activities of both enzymes, but especially of mannan synthetase,
      drop to a low value. Furthermore, the activities of both enzymes are distributed
      in the cell along an apical-basal gradient. High activities are present in the
      apical regions of the cell where growth and mannan synthesis mainly occur,
      whereas in the basal region, growth, mannan synthesis and the activity of the two
      enzymes are slight. Since the in vitro activity of GDP-Man-pyr is at least 100
      times higher than that of mannan synthetase, it was concluded that mannan
      synthetase activity is the limiting factor in mannan synthesis. This conclusion
      is supported by the determined pool sizes of Fru 6-P, Man 6-P, Man 1-P and GDP
      Man during the development of the cells. The control of mannan synthesis and with
      it cell wall formation and growth through the regulation of mannan synthetase
      activity is discussed. 

PMID- 24317760
TI  - Relationship of indole-3-acetic acid and tryptophan concentrations in normal and
      5-methyltryptophan-resistant cell lines of wild carrots.
AB  - A 5-methyltryptophan(5-MT)-resistant cell line of wild carrot (Daucus carota L.),
      W001, that exhibited auxin-independent callus growth, was found to accumulate
      indole-3-acetic acid (IAA) and tryptophan (trp). Anthranilate-synthetase activity
      in W001 cell extract was less sensitive to feedback inhibition by trp than in the
      original 5-MT-sensitive cell lines. It is hypothesized that the resistant enzyme
      allowed more trp synthesis and accumulation which, in turn, affected the IAA
      concentration in the cell. Since carrot cultures cannot regenerate in the
      presence of exogenous auxin, the elevated IAA concentration in W001 may be
      responsible for its drastically reduced capacity to regenerate. The relationship
      between trp and IAA levels was further investigated by examining the effect of
      2,4-dichlorophenoxy acetic acid (2,4-D) on the endogenous concentration of trp
      and IAA. In general, the IAA level was reduced but the trp concentration was
      elevated when 2,4-D was present in the culture medium. 

PMID- 24317761
TI  - Reversible blockage of the cell cycle in the meristem of Riella helicophylla
      (Bory et Mont.) Mont. by p-chlorophenoxyisobutyric acid (PCIB).
AB  - Treatment of gemmae of Riella helicophylla with PCIB results in reversible
      blockage of the meristematic cells in the G1-phase. At the same time the normal
      subdivision of the intercalary meristem into two lateral meristems disappears.
      PCIB is effective only when the plants are exposed to light. 

PMID- 24317762
TI  - Biosynthesis of ferredoxin in Chlamydomonas reinhardii.
AB  - The selective action of the antibiotics chloramphenicol and cycloheximide on the
      synthesis of ferredoxin in liquid cultures of Chlamydomonas reinhardii was
      studied. Highly specific antibodies raised against Chlamydomonas ferredoxin were
      used to determine the in vivo synthesis of apoferredoxin and conversion into
      native protein. The results indicate that 80S ribosomes are involved in the
      synthesis. Chlamydomonas cells growing in the absence of iron did not synthesize
      immunologically detectable amounts of ferredoxin. We suggest that this is based
      upon feed-back inhibition of apoferredoxin synthesis at the translational level. 

PMID- 24317763
TI  - Crassulacean acid metabolism (CAM) in leaves of Aloe arborescens mill :
      Comparative studies of the carbon metabolism of chlorenchym and central
      hydrenchym.
AB  - In the succulent leaves of Aloe arborescens Mill diurnal oscillations of the
      malic acid content, being indicative of Crassulacean Acid Metabolism (CAM), were
      exhibited only by the green mesophyll. In contrast, the malic acid level of the
      central chloroplast-free water-storing tissue remained constant throughout the
      day-night cycle. Apart from malate, the green tissue contained high amounts of
      isocitrat which was lacking in the water tissue. There was no significant
      transfer from the green mesophyll to the water tissue of (14)C fixed originally
      via dark (14)CO2 fixation in the mesophyll. Both isolated mesophyll and water
      tissue were capable of dark CO2 fixation yielding mainly malate as the first
      stable product. Both tissues have phosphoenolpyruvate carboxylase. However, the
      enzymes derived from the both sources could be distinguished by their molecular
      weights and by their kinetic properties, suggesting different phosphoenolpyruvate
      carboxylase proteins. The conclusion drawn from the experiments is that in a.
      arborescens the CAM cycle proceeds exclusively in the green mesophyll and that
      the water tissue, though capable of malate synthesis via beta-carboxylation of
      phosphoenolpyruvate, behaves as an independent metabolic system where CAM is
      lacking. This view is supported by the finding that the cell walls bordering the
      green mesophyll from the water tissue lack plasmodesmata, hence conveniant
      pathways of metabolite transport. 

PMID- 24317764
TI  - Cold-sensitive expression of cytokinin habituation by tobacco pith cells in
      culture.
AB  - Cloned, cytokinin-habituated tissues of Nicotiana tobacum L. cv. "Havana 425" are
      able to grow in culture at 25 degrees  C without added cytokinin. These tissues
      vary in their expression of the habituated phenotype at 16 degrees  C. When
      cytokinin-requiring pith tissues are converted to the habituated state by 35
      degrees  C treatment, all of the habituated cells are cold sensitive. After
      several transfers in culture, some of these habituated cells give rise to stable,
      cold resistant variants. Both phenotypes are inherited by individual cells. Cold
      sensitive clones at 16 degrees  C and non-habituated clones at 16 degrees  C as
      well as 25 degrees  C show the same dose response to the cytokinin, kinetin. This
      suggests that at the physiological level, cold sensitivity results from a
      decreased production of cell division factors rather than from a decreased
      affinity of cellular receptors for these factors. 

PMID- 24317765
TI  - Selection of somatic hybrids after fusion of protoplasts from Datura innoxia
      Mill. and Atropa belladonna L.
AB  - After fusion of protoplasts from a diploid (2n=24) and a tetraploid (4n=48)
      chlorophyll-deficient mutant of Datura innoxia Mill. with diploid (2n=72) green
      wild-type protoplasts of Atropa belladonna L. thirteen somatic hybrids could be
      selected, most of which had already started to produce leaves and shoots. Hybrid
      calli were recognizable by the production of hairs, typical for Datura innoxia,
      and the green colour, derived from Atropa belladonna. Further proof for the
      hybrid nature was furnished by cytological investigations. The metaphase
      chromosomes of both species are easily distinguishable in their size: chromosomes
      of Datura innoxia are about twice as large as those of Atropa belladonna. The
      chromosome numbers of the hybrids varied from ca. 84 to ca. 175. 

PMID- 24317766
TI  - Reversible inhibition of the calvin cycle and activation of oxidative pentose
      phosphate cycle in isolated intact chloroplasts by hydrogen peroxide.
AB  - Hydrogen peroxide (6x10(-4) M) causes a 90% inhibition of CO2-fixation in
      isolated intact chloroplasts. The inhibition is reversed by adding catalase (2500
      U/ml) or DTT (10 mM). If hydrogen peroxide is added to a suspension of intact
      chloroplasts in the light, the incorporation of carbon into hexose- and heptulose
      bisphosphates and into pentose monophosphates is significantly increased,
      whereas; carbon incorporation into hexose monophosphates and ribulose 1,5
      bisphosphate is decreased. At the same time formation of 6-phosphogluconate is
      dramatically stimulated, and the level of ATP is increased. All these changes
      induced by hydrogen peroxide are reversed by addition of catalase or DTT.
      Additionally, the conversion of [(14)C]glucose-6-phosphate into different
      metabolites by lysed chloroplasts in the dark has been studied. In presence of
      hydrogen peroxide, formation of ribulose-1,5-bisphosphate is inhibited, whereas
      formation of other bisphosphates,of triose phosphates, and pentose monophosphates
      is stimulated. Again, DTT has the opposite effect. The release of (14)CO2 from
      added [(14)C]glucose-6-phosphate by the soluble fraction of lysed chloroplasts
      via the reactions of oxidative pentose phosphate cycle is completely inhibited by
      DTT (0.5 mM) and re-activated by comparable concentrations of hydrogen peroxide.
      These results indicate that hydrogen peroxide interacts with reduced sulfhydryl
      groups which are involved in the light activation of enzymes of the Calvin cycle
      at the site of fructose- and sedoheptulose bisphophatase, of phosphoribulokinase,
      as well as in light-inactivation of oxidative pentose phosphate cycle at the site
      of glucose-6-phosphate dehydrogenase. 

PMID- 24317767
TI  - Increase in chloroplastic thiol groups by SO2 and its effect on light modulation
      of NADP-dependent glyceraldehyde 3-phosphate dehydrogenase.
AB  - In broken spinach chloroplasts the total amount of thiol groups is about 3.7
      MUmol mg(-1) chlorophyll. Two thirds are represented by the masked form (which is
      only titratable after unfolding of the protein). Of the free groups, those
      reacting with NBD.Cl (1.2-2.0 MUmol mg(-1) chlorophyll) seem to be undergoing
      oxidation more readily than those reacting with DTNB (1.0 MUmol mg(-1)
      chlorophyll). SO2 application causes a maximal increase of 25% in free thiols,
      and doubles the amount of the masked thiols. The light triggered increase in SH,
      which starts at an elevated level, runs parallel to that of the controls. SO2
      application of 1.8 mg m(-3) (=28 nmol l(-1)) for 1 h does not affect the dark
      level of NADP-GPD but enhances the light modulation by increasing the ratio of
      activation. This enhancement is explained by an increase in masked thiol groups
      during the preceding fumigation period. 

PMID- 24317768
TI  - The stability of the postulated wall-loosening enzyme in acid-induced growth.
AB  - Long-term pretreatments with cycloheximide (CH) caused inhibition of subsequent
      acidinduced growth of Avena coleoptile segments, but only after 6 or more h of CH
      treatment. These results together with previous, published evidence with frozen
      thawed tissue are consistent with the hypothesis that there exists a wall
      loosening enzyme responsible for acid-induced elongation and that it has a half
      life of at least 7-8 h. 

PMID- 24317769
TI  - Carbon dioxide fixation by chloroplasts isolated in glycinebetaine : A putative
      cytoplasmic osmoticum.
AB  - Spinach chloroplasts capable of high rates of CO2 fixation have been isolated in
      glycinebetaine as an alternative osmoticum to sorbitol and found to be very
      stable. Proline was a less satisfactory alternatine. The possible significance of
      the use of glycinebetaine is discussed as this solute may be the physiological
      cytoplasmic osmoticum in members of the Chenopodiaceae. 

PMID- 24317770
TI  - The regulation of K(+) influx in excised barley roots : Relationships between
      K(+) influx and electrochemical potential differences.
AB  - The electrochemical potential differences [Formula: see text] for potassium,
      between excised barley (Hordeum vulgare L.) roots and external media containing
      0.05 mM KCl+0.5 mM CaSO4, were determined over a 4-h period during which
      initially low-K(+) roots accumulated K(+) by pretreatment in 50 mM KCl plus 0.5
      mM CaCl2. This pretreatment resulted in increased internal [K(+)], decreased K(+)
      influx (as measured from 0.05 mM KCl+0.5 mM CaSO4) and decreased values of
      [Formula: see text]. These observations indicate that the decline of K(+) influx
      associated with increased internal K(+) concentration cannot be accounted for by
      passive adjustment to the electrochemical gradient for this ion. 

PMID- 24317771
TI  - Cytoplasmic streaming in the root cortex and its role in the delivery of
      potassium to the shoot.
AB  - The influence of cytochalasin B (CB), a potent inhibitor of cytoplasmic
      streaming, on (86)Rb-labelled K(+) translocation by detopped Lycopersicon
      esculentum Mill., Cucumis sativus L. and Zea mays L. plants was examined by
      measuring the radioactivity in xylem exudate before and after the addition of CB
      to the medium bathing the roots. CB caused complete cessation of cytoplasmic
      streaming in root segments within 15 min but was without effect on either total
      (86)Rb uptake or exudation. Thus factors other than cytoplasmic streaming limit
      the movement of K(+) across the symplast of the root of higher plants. 

PMID- 24317772
TI  - Kinetics of the light-induced georeactivity of maize roots.
AB  - Apical root segments of Zea mays L. cv. Orla 264 undergo some geotropic curvature
      in complete darkness but the curvature increases considerably if prior to
      geostimulation the segments are given a light pretreatment. If the light
      treatment is follwed by a dark treatment before the root is geostimulated the
      light-induced response is not changed by dark periods up to 2 h but declines with
      longer ones, and disappears completely after 5 h of darkness. 

PMID- 24317773
TI  - Models of adulthood: An ethnographic study of an adolescent peer group.
AB  - In this article a middle class adolescent peer group is studied in a community
      setting using ethnographic techniques. The purpose of the study is to describe
      the group's relationship to adults and to uncover the adult reference group after
      which the group modeled itself. Although this group was organized to help poor
      people in the United States and abroad and had extensive contact with adults who
      could be described as change agents working to close the economic gap between
      rich and poor, this group modeled itself after middle class adult managers. The
      youths were attracted to the change agent adults only in so far as they satisfied
      their desire for equal status interaction with adults. Attempts by the group to
      establish closer contact with their adult models were in conflict with their
      desire to maintain autonomy from adult domination. The concluding section
      compares the findings of this study to two ethnographic studies of adolescent
      groups that used secondary school sites. 

PMID- 24317774
TI  - Profiles of children's psychological states derived from the Gottschalk-Gleser
      content analysis of speech.
AB  - Comparison of 17 different scores, obtained with the Gottschalk-Gleser content
      analysis scales, with norms for White and Black children has now been made easily
      possible by the development of two types of profile forms. The scores derived by
      this method are transformed by plotting them, on a grid, to standard scores. Form
      1 provides a nonlinear transformation that does correct for skewness of the score
      distribution. Form 2 provides a linear transformation that does not correct for
      skewness. These forms can be used to examine patterns and trends pictorially in
      psychological state or trait scores derived from speech by this method. 

PMID- 24317775
TI  - Content scaling of affect in adolescent speech samples.
AB  - Data are reported which extend the applicability of the Gottschalk-Gleser scales
      for the content analysis of speech samples to adolescents. The data were gathered
      on 112 youngsters aged 11-18 stratified by age, race, and sex in a balanced
      design. Girls had higher Anxiety scores and relatively lower scores on Hostility
      Directed Inward, Ambivalent Hostility, and Social Alienation and Personal
      Disorganization than did boys. Blacks spoke less words and expressed more Overt
      Hostility Outward than did Whites. These latter scores increased with age, as did
      Hostility Directed Inward. The affect scores for this normative group are also
      compared to those for "normal" adults and to an adolescent clinic and a juvenile
      delinquent population. Correlations with three paper-and-pencil inventories
      (Adolescent Life Assessment Checklist, Defense Mechanisms Inventory, and Rotter I
      E scale) are presented. 

PMID- 24317776
TI  - Friends' interests: A cluster-analytic study of college student peer
      environments, personality, and behavior.
AB  - A 27-item measure was developed to assess college peer environments in terms of
      friends' interests as perceived by individual students. Four dimensions of
      friends' interests were identified in cluster analyses: Collegiate Activities,
      Intellectual Pursuits, Apathy or Alienation, and Traditional Adult Orientation.
      In contrast to previous studies that have focused on peer environment
      characteristics which were "proximal" to specific behaviors, the comparatively
      "distal" Friends' Interests dimensions were capable of accounting for variation
      on an array of social, psychological, and behavioral measures. In general, the
      Collegiate and Traditional clusters were related to a relatively conventional set
      of individual personality and behavioral variables among college-age men and
      women; on the other hand, the Intellectual and Apathy dimensions were associated
      with more unconventional or liberal personality characteristics and behaviors. 

PMID- 24317777
TI  - Ego identity status and values among high school females.
AB  - To test the hypothesis that adolescent females who are high in ego identity have
      high interests in religious and political values, the relationship between the
      ego identity status of 80 senior high school females and their response to the
      Allport-Vernon-Lindzey Study of Values was examined. Participants classified as
      being identity achievements, moratoriums, and foreclosures had higher religious
      value scores than did diffusions; however, the expected differences on political
      value scores were not found. Two-thirds of the identity achievers came from homes
      disrupted by divorce or death of one parent, while less than 20% of the members
      of the other three statuses came from broken homes. 

PMID- 24317778
TI  - Ego identity status and expressive writing among high school and college
      students.
AB  - Several studies were conducted to assess the relationship between expressive
      writing (poetry writing and journal keeping) and ego identity development among
      high school and college students. In three independent comparisons, poetry
      writers were more likely than students not writing poetry to have previously
      resolved identity crises (i.e., to be in the identity achiever status). There
      were also indications that students who had never written poetry were more likely
      to be in the foreclosure and identity diffusion statuses. No differences in
      identity development were found between students keeping personal journals and
      those who had not kept journals. A comparison was made of the themes most
      frequently chosen as the subject for each type of expressive writing and the
      functions such writings were believed to be serving. Possible explanations for
      why poetry writing, but not journal keeping, is related to ego identity formation
      are discussed. 

PMID- 24317779
TI  - Portrait of the North American runaway: A critical review.
AB  - Runaway behavior has been viewed as a psychopathological problem by many.
      However, a review of the available research literature questions this
      perspective. An examination of the reported psychological profile of runaways
      suggests no clear relationship between personality and runaway behavior. Further,
      a multiplicity of factors can be noted which are potential causal agents for
      running away. These factors range from sociocultural values to school problems.
      Runaway research is shown to be methodologically limited by several factors, but
      the data are suggestive. Also, the authors conclude that future research on this
      growing social problem might utilize an "alternative values" or "deindivuation
      model" in generating testable hypotheses about runaway behavior. 

PMID- 24317780
TI  - Comment on Wang et al.: a meta-analysis of plate fixation versus intramedullary
      nailing for humeral shaft fractures.

PMID- 24317781
TI  - Prevalence of FA-D2 rare complementation group of Fanconi anemia in Serbia.
AB  - OBJECTIVE: To investigate genetic subtypes of inherited bone marrow failure
      syndrome Fanconi anemia (FA) in Sebia. FA-D2 subtype was found to be the most
      frequent genetic subtype among investigated FA patients; specific observations of
      FA-D2 phenotype are pointed out. METHODS: Several biological endpoints of FA
      cells in vitro such as radiation-induced level of lymphocyte micronuclei
      (radiosensitivity), base line and radiation induced level of the DNA double
      strand breaks (DSBs), leukocyte apoptosis, and telomere capping function were
      assessed. RESULTS: The results indicate that all FA-D2 patients display
      radioresistant in vitro response, which is seen as significantly reduced yield of
      radiation-induced micronuclei. On the contrary, FA-A patients display
      radiosensitive in vitro response seen as increased number of radiation-induced
      micronuclei (MN). A massive elimination of irradiated cells via apoptosis is
      found in both FA-A and FA-D2 subtypes. In FA-A subtype apoptosis positively
      relates with the yield of radiation-induced MN, whereas in FA-D2 subtype
      apoptosis relates with a high percentage of cells carrying dysfunctional
      telomeres. The present results unequivocally demonstrate that cytokinesis-block
      micronucleus (CBMN) assay and analyses of telomere capping function can be used
      to distinguish FA-D2 and FA-A complementation groups. CONCLUSIONS: Considering
      all biological endpoints were analyzed, it can be concluded that all FA patients
      are radiosensitive, regardless of their complementation group. Thus, using CBMN
      test and telomere capping function analysis can discriminate FA-A from FA-D2
      complementation groups, which could be important for assessment the conditioning
      regimens prior to bone marrow transplantation.

PMID- 24317782
TI  - Camphor poisoning: a rare but preventable cause of status epilepticus.

PMID- 24317783
TI  - Mini review of mercury contamination in environment and human with an emphasis on
      Malaysia: status and needs.
AB  - This article provides an overview of research on mercury (Hg) contamination in
      Malaysia and its evolution from 1979 to 2012. The objective of this paper was to
      review and provide an understanding of Hg exposures in the environment, humans,
      and food in Malaysia. Hg concentration in the environment is high in areas of
      West Port, Malacca Straits, Prai, and Johor because these areas receive
      anthropogenic metal loads brought about by industrial activities. Hg
      concentration in humans is related to seafood intake (dietary), environmental
      conditions, and different geographical locations. Hg levels in food showed higher
      concentration in the West coast of Peninsular Malaysia. Hg concentration is also
      present in the country's tropical fruits, which is related to agrochemical and
      fertilizer usage. This review showed that there is an urgent need to identify Hg
      toxicology and bioaccumulation as well as the health effects of Hg exposure in
      different ecological compartments. This review aims to provide helpful
      recommendations for future Hg biomonitoring and research in Malaysia.

PMID- 24317784
TI  - Ethics and law in research with human biological samples: a new approach.
AB  - During the last century a large number of documents (regulations, ethical codes,
      treatises, declarations, conventions) were published on the subject of ethics and
      clinical trials, many of them focusing on the protection of research
      participants. More recently various proposals have been put forward to relax some
      of the constraints imposed on research by these documents and regulations. It is
      important to distinguish between risks deriving from direct interventions on
      human subjects and other types of risk. In Italy the Data Protection Authority
      has acted in the question of research using previously collected health data and
      biological samples to simplify the procedures regarding informed consent. The new
      approach may be of help to other researchers working outside Italy.

PMID- 24317785
TI  - Distinct localization of septin proteins to ciliary  sub-compartments in airway
      epithelial cells.
AB  - Mucociliary clearance of the airways is accomplished by cilia-mediated laminar
      mucus flow along the planar epithelial surface. Maintenance of the highly
      specific architecture of the ciliated airway epithelium with columnar-shaped
      epithelial cells and tightening of the epithelial barrier is mainly attributed to
      the F-actin cytoskeleton. Recently, members of the highly conserved family of
      septin proteins have been shown to play crucial roles in ciliated tissue. These
      GTP-binding proteins form hetero-oligomeric complexes and assemble higher-order
      cytoskeletal structures such as filaments, bundles and ring-like structures such
      as a membrane diffusion barrier at the ciliary base. Here we analyzed the
      subcellular and sub-ciliary localization of various septin proteins by
      immunofluorescence imaging of airway epithelial cells. In addition to cytoplasmic
      localization we found that septins are either enriched at the apical cell cortex
      including the ciliary bases (septin-2, -4, -6, and -7), or show axonemal staining
      (septin-2, -7, -9 and -11) or specifically localize to ciliary sub-compartments
      (septin-8 and -9). The distinct localization of septins suggests structural
      functions as cytoskeletal components and as elements of the mechanical barrier at
      the apical cell cortex. Furthermore, the tight association of septin-8 and -9
      with the ciliary compartment indicates a possible involvement in cilia-specific
      functions and cilia-related diseases.

PMID- 24317786
TI  - Red blood cell distribution width predicts survival in patients with Eisenmenger
      syndrome.
AB  - BACKGROUND: Previous studies identified an independent relationship between red
      blood cell distribution width (RDW) and prognosis in patients with pulmonary
      hypertension of mixed etiologies and idiopathic pulmonary arterial hypertension.
      This study aimed to investigate the significance of RDW for predicting survival
      in patients with Eisenmenger syndrome (ES). METHODS: We retrospectively reviewed
      the clinical records and collected baseline data for patients newly diagnosed
      with ES in our hospital between January 2005 and October 2009. Follow-up data
      were collected periodically using a specifically designed network database until
      December 31, 2012. The end point was all-cause death. RESULTS: A total of 109
      patients with ES were included in the study. Twenty-one patients (19.3%) died
      during a median follow-up period of 4.2 years (interquartile range 3.7-5.0
      years). Baseline RDW was significantly correlated with mixed venous oxygen
      saturation (r=-0.286, p=0.003), arterial oxygen saturation (r=-0.423, p<0.001),
      mean pulmonary arterial pressure (r=0.271, p=0.004) and total pulmonary
      resistance (r=0.465, p<0.001). The 1-, 3- and 5-year survival rates for all 109
      patients were 94%, 87% and 78%, respectively. Kaplan-Meier analysis showed that
      patients with RDW >=13.9% had a lower survival rate than patients with RDW <13.9%
      (p=0.001). Multivariate Cox regression analysis showed that RDW was an
      independent prognostic marker in ES, with a hazard ratio of 1.162 (95% CI 1.036
      1.302; p=0.010). CONCLUSIONS: Baseline RDW correlates with hemodynamics and is an
      independent prognostic marker in ES.

PMID- 24317787
TI  - Knowing self and caring through service learning.
AB  - Professional caring is the essence of nursing practice. Reflection on personal
      assumptions and beliefs challenge stereotypic views that influence professional
      caring and nursing care. An innovative educational pedagogy known as service
      learning creates an opportunity for students to reflect on self in the context of
      service to others; it is through this pedagogy that personal assumptions and
      beliefs are challenged as students become registered nurses. A qualitative
      descriptive study engaged undergraduate first and second year nursing students
      through interviews and reflections. The purposes of this study were to describe
      students' perception of self and caring in service learning, any changes in the
      perceptions of self over time, and the connection of self to others. Results
      identified three major themes: understanding self, becoming a nurse and learning
      to care with increasing depth over the two years. Implications for nursing
      curriculum and further research are discussed.

PMID- 24317788
TI  - Teaching experiences of second degree accelerated baccalaureate nursing faculty.
AB  - Despite the extraordinary growth of accelerated second degree baccalaureate
      nursing programs, little research has been conducted about the experiences of
      faculty teaching these students. Using a hermeneutic phenomenological approach,
      this study explored the experiences of 14 accelerated second degree baccalaureate
      faculty from the eastern region of the United States. The data revealed that many
      faculty teaching second degree students feel unprepared and want guidance on how
      to teach these students, which was identified in the theme, Figuring It Out On My
      Own. This article describes this study and the implications of this theme for
      faculty recruitment and retention in accelerated second degree baccalaureate
      nursing programs.

PMID- 24317789
TI  - Reading Ella: using literary patients to enhance nursing students' reflective
      thinking in the classroom.
AB  - This action research study was designed to explore, in-depth, how 70 senior
      nursing students experienced an assignment that involved reading and reflecting
      on a short story, Ella, and the educator's experience during the process. Four
      sources of data were collected: student reflections, field notes, a classroom
      process recording by an expert educator/observer, and a focus group interview.
      Four themes emerged: (1) student reflections revealed their inner, often hidden
      landscapes; (2) Ella prompted clarification of the past and/or triggered future
      projective thinking; (3) Ella clarified difficult-to-teach concepts; and (4) the
      interface between students' thoughts and teacher responses provided a platform of
      connectivity. I propose that reading well-written stories may enhance students'
      clinical reasoning skills and ethical comportment within the confines of a
      classroom. In addition, when students are introduced to literary patients like
      Ella, they can dwell with the characters at a more peaceful pace which, in
      itself, may encourage reflectivity.

PMID- 24317790
TI  - Accelerated baccalaureate nursing students use of emotional intelligence in
      nursing as "caring for a human being": a mixed methods grounded theory study.
AB  - Accelerated nursing students are ideal informants regarding abstract nursing
      concepts. How emotional intelligence (EI) is used in nursing remains a relatively
      elusive process that has yet to be empirically modeled. The purpose of this study
      was to generate a theoretical model that explains how EI is used in nursing by
      accelerated baccalaureate nursing students. Using a mixed methods grounded theory
      study design, theoretical sampling of EI scores directed sampling for individual
      interviews and focus groups. Caring for a human being emerged as the basic social
      process at the heart of which all other processes--Getting it; Being caring; The
      essence of professional nurse caring; Doing something to make someone feel
      better; and Dealing with difficulty--are interconnected. In addition to a
      theoretical explanation of the use of EI in nursing, this study corroborates
      findings from other qualitative studies in nursing and contributes a rich
      description of accelerated baccalaureate nursing students and an example of a
      mixed methods study design to the small but growing literature in these areas.

PMID- 24317791
TI  - A Bayesian decision procedure for testing multiple hypotheses in DNA microarray
      experiments.
AB  - DNA microarray experiments require the use of multiple hypothesis testing
      procedures because thousands of hypotheses are simultaneously tested. We deal
      with this problem from a Bayesian decision theory perspective. We propose a
      decision criterion based on an estimation of the number of false null hypotheses
      (FNH), taking as an error measure the proportion of the posterior expected number
      of false positives with respect to the estimated number of true null hypotheses.
      The methodology is applied to a Gaussian model when testing bilateral hypotheses.
      The procedure is illustrated with both simulated and real data examples and the
      results are compared to those obtained by the Bayes rule when an additive loss
      function is considered for each joint action and the generalized loss 0-1
      function for each individual action. Our procedure significantly reduced the
      percentage of false negatives whereas the percentage of false positives remains
      at an acceptable level.

PMID- 24317792
TI  - Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF
      kappaB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant
      activity and inhibition of apoptosis.
AB  - AIMS/HYPOTHESIS: Chronic inflammatory processes have been increasingly shown to
      be involved in the pathogenesis of diabetes and diabetic nephropathy. Recently,
      we demonstrated that a lectin-like domain of thrombomodulin (THBD), which is
      known as THBD domain 1 (THBDD1) and which acts independently of protein C
      activation, neutralised an inflammatory response in a mouse model of sepsis.
      Here, therapeutic effects of gene therapy with adeno-associated virus (AAV)
      carried THBDD1 (AAV-THBDD1) were tested in a mouse model of type 2 diabetic
      nephropathy. METHODS: To assess the therapeutic potential of THBDD1 and the
      mechanisms involved, we delivered AAV-THBDD1 (10(11) genome copies) into db/db
      mice and tested the effects of recombinant THBDD1 on conditionally immortalised
      podocytes. RESULTS: A single dose of AAV-THBDD1 improved albuminuria, renal
      interstitial inflammation and glomerular sclerosis, as well as renal function in
      db/db mice. These effects were closely associated with: (1) inhibited activation
      of the nuclear factor kappaB (NF-kappaB) pathway and the NACHT, LRR and PYD
      domains-containing protein 3 (NLRP3) inflammasome; (2) promotion of nuclear
      factor (erythroid-derived 2)-like 2 (NRF2) nuclear translocation; and (3)
      suppression of mitochondria-derived apoptosis in the kidney of treated mice.
      CONCLUSIONS/INTERPRETATION: AAV-THBDD1 gene therapy resulted in improvements in a
      model of diabetic nephropathy by suppressing the NF-kappaB-NLRP3 inflammasome
      mediated inflammatory process, enhancing the NRF2 antioxidant pathway and
      inhibiting apoptosis in the kidney.

PMID- 24317793
TI  - beta-Arrestin2 plays a key role in the modulation of the pancreatic beta cell
      mass in mice.
AB  - AIMS/HYPOTHESIS: Beta cell failure due to progressive secretory dysfunction and
      limited expansion of beta cell mass is a key feature of type 2 diabetes. Beta
      cell function and mass are controlled by glucose and hormones/neurotransmitters
      that activate G protein-coupled receptors or receptor tyrosine kinases. We have
      investigated the role of beta-arrestin (ARRB)2, a scaffold protein known to
      modulate such receptor signalling, in the modulation of beta cell function and
      mass, with a specific interest in glucagon-like peptide-1 (GLP-1), muscarinic and
      insulin receptors. METHODS: beta-arrestin2-knockout mice and their wild-type
      littermates were fed a normal or a high-fat diet (HFD). Glucose tolerance,
      insulin sensitivity and insulin secretion were assessed in vivo. Beta cell mass
      was evaluated in pancreatic sections. Free cytosolic [Ca(2+)] and insulin
      secretion were determined using perifused islets. The insulin signalling pathway
      was evaluated by western blotting. RESULTS: Arrb2-knockout mice exhibited
      impaired glucose tolerance and insulin secretion in vivo, but normal insulin
      sensitivity compared with wild type. Surprisingly, the absence of ARRB2 did not
      affect glucose-stimulated insulin secretion or GLP-1- and acetylcholine-mediated
      amplifications from perifused islets, but it decreased the islet insulin content
      and beta cell mass. Additionally, there was no compensatory beta cell mass
      expansion through proliferation in response to the HFD. Furthermore, Arrb2
      deletion altered the islet insulin signalling pathway.
      CONCLUSIONS/INTERPRETATION: ARRB2 is unlikely to be involved in the regulation of
      insulin secretion, but it is required for beta cell mass plasticity.
      Additionally, we provide new insights into the mechanisms involved in insulin
      signalling in beta cells.

PMID- 24317795
TI  - Summer rainfall variability in European Mediterranean mountains from the
      sixteenth to the twentieth century reconstructed from tree rings.
AB  - Since the end of the last glacial period, European Mediterranean mountains have
      provided shelter for numerous species of Eurosiberian and Boreal origin. Many of
      these species, surviving at the southern limit of their range in Europe and
      surrounded by Mediterranean ones, are relatively intolerant to summer drought and
      are in grave danger of loss, as a result of increasingly long and frequent
      droughts in this region. This is the case of the Scots pine (Pinus sylvestris)
      and the Austrian pine (Pinus nigra ssp. salzmannii) which are found on Central
      Iberian Peninsula at the edge of their natural range. We used a tree ring network
      of these two species to reconstruct past variations in summer rainfall. The
      reconstruction, based upon a tree ring composite chronology of the species, dates
      back to 1570 (adjusted R(2) = 0.49, P < 0.000001) and captures interannual to
      decadal scale variability in summer precipitation. We studied the spatial
      representativeness of the rainfall patterns and described the occurrence rate of
      extremes of this precipitation. To identify associations between macroclimatic
      factors and tree radial growth, we employed a principal component analysis to
      calculate the resultant of the relationship between the growth data of both
      species, using this resultant as a dependent variable of a multiple regression
      whose independent variables are monthly mean temperature and precipitation from
      the average records. Spatial correlation patterns between instrumental
      precipitation datasets for southern Europe and reconstructed values for the 1950
      1992 period indicate that the reconstruction captures the regional signal of
      drought variability in the study region (the origin of this precipitation is
      convective: thermal low pressure zones induced in the inland northeastern areas
      of the Iberian Peninsula). There is a clear increase in the recurrence of extreme
      dry events as from the beginning of twentieth century and an abrupt change to
      drier conditions. There appears to be a tendency toward recurrent exceptionally
      dry summers, which could involve a significant change for the Eurosiberian
      refugee species.

PMID- 24317796
TI  - Rapid prototyping to design a customized locking plate for pancarpal arthrodesis
      in a giant breed dog.
AB  - This report describes the treatment of traumatic carpal hyperextension in a giant
      breed dog by pancarpal arthrodesis using a custom-made Fixin locking plate,
      created with the aid of a three-dimensional plastic model of the bones of the
      antebrachium produced by rapid prototyping technology. A three-year-old 104 kg
      male Mastiff dog was admitted for treatment of carpal hyperextension injury.
      After diagnosis of carpal instability, surgery was recommended. Computed
      tomography images were used to create a life-size three-dimensional plastic model
      of the forelimb. The model was used as the basis for constructing a customized 12
      hole Fixin locking plate. The plate was used to attain successful pancarpal
      arthrodesis in the animal. Radiographic examination after 74 and 140 days
      revealed signs of osseous union of the arthrodesis. Further clinical and
      radiographic follow-up examination three years later did not reveal any changes
      in implant position or complications. 

PMID- 24317797
TI  - The binding mechanisms of intrinsically disordered proteins.
AB  - Intrinsically disordered proteins (IDPs) and intrinsically disordered regions
      (IDRs) of proteins are very common and instrumental for cellular signaling.
      Recently, a number of studies have investigated the kinetic binding mechanisms of
      IDPs and IDRs. These results allow us to draw conclusions about the energy
      landscape for the coupled binding and folding of disordered proteins. The
      association rate constants of IDPs cover a wide range (10(5)-10(9) M(-1) s(-1))
      and are largely governed by long-range charge-charge interactions, similarly to
      interactions between well-folded proteins. Off-rate constants also differ
      significantly among IDPs (with half-lives of up to several minutes) but are
      usually around 0.1-1000 s(-1), allowing for rapid dissociation of complexes.
      Likewise, affinities span from pM to MUM suggesting that the low-affinity high
      specificity concept for IDPs is not straightforward. Overall, it appears that
      binding precedes global folding although secondary structure elements such as
      helices may form before the protein-protein interaction. Short IDPs bind in
      apparent two-state reactions whereas larger IDPs often display complex multi-step
      binding reactions. While the two extreme cases of two-step binding
      (conformational selection and induced fit) or their combination into a square
      mechanism is an attractive model in theory, it is too simplistic in practice.
      Experiment and simulation suggest a more complex energy landscape in which IDPs
      bind targets through a combination of conformational selection before binding
      (e.g., secondary structure formation) and induced fit after binding (global
      folding and formation of short-range intermolecular interactions). 

PMID- 24317798
TI  - Early and long-term outcomes of coronary artery bypass grafting and percutaneous
      coronary intervention in patients with left main disease: single-center results
      of multidisciplinary decision making.
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) is considered the standard
      treatment for patients with left main disease (LMD). However, percutaneous
      coronary intervention (PCI) has recently emerged as a treatment option for
      selected patients. We assessed early and long-term outcomes of patients with LMD
      who underwent either CABG or PCI in our institution. METHODS: We reviewed the
      records of 438 patients with LMD who underwent revascularization between January
      2005 and December 2010. Treatment modality, chosen by our heart team, was CABG in
      409 patients and PCI in 29. Age, prevalence of women, and mean ejection fraction
      of patients were not significantly different between groups. Mean logistic
      European system for cardiac operative risk evaluation score was 7.7. Mean follow
      up was 37.1 months. RESULTS: In CABG group, mean number of anastomoses was 4.0
      and complete revascularization was achieved in 97.1 %. Bilateral internal
      thoracic arteries were used in 87.0 %. In PCI group, mean number of stents was
      1.3 and complete revascularization was achieved in 44.8 %. Drug-eluting stent was
      used in 72.4 %. In-hospital mortality was 1.1 % (1.0 %, CABG group vs. 3.4 %, PCI
      group; p = 0.29). At 3 years, overall survival was 94.3 % (95.3 vs. 81.1 %; p <
      0.01) and rate of freedom from major adverse cardiac events and cerebrovascular
      accidents was 88.9 % (89.8 vs. 77.3 %; p = 0.05). CONCLUSIONS: Our heart team's
      approach resulted in favorable overall results in patients with LMD.
      Multidisciplinary decision making in these high-risk patients can make good long
      term outcomes in CABG.

PMID- 24317799
TI  - Effects of inorganic carbon accumulation on photosynthetic oxygen reduction and
      cyclic electron flow in the cyanobacterium Synechococcus PCC7942.
AB  - This paper examines the effect of inorganic carbon transport and accumulation in
      Synechococcus PCC7942 on fluorescence quenching, photosynthetic oxygen reduction
      and both linear and cyclic electron flow. The data presented support the previous
      findings of Miller et al. (1991) that the accumulation of Ci by the CO2
      concentrating mechanism is able to stimulate oxygen photoreduction, particularly
      so when CO2 fixation is inhibited by PCR cycle inhibitors such as glycolaldehyde.
      This effect is found with both high and low-Ci grown cells, but the potential for
      oxygen photoreduction is about two-fold higher in low-Ci grown cells. This
      greater potential for O2 photoreduction is also correlated with a higher ability
      of low-Ci cells to photoreduce H2O2. Experiments with a mutant which transports
      Ci but does not accumulate it internally, indicates that the stimulation of O2
      photoreduction appears to be a direct effect of the internal accumulation of Ci
      rather than from its participation in the transport process. In the absence of
      Ci, no specific partial reactions of photosynthetic electron transport appear to
      be inhibited, and the PS 1 acceptors PNDA and MV as well as the PS 2 acceptor DMQ
      can all run electron transport at levels approaching those during active CO2
      fixation. Measurements of P700(+) show that when the cells are depleted of Ci
      during photosynthesis, P700 becomes more oxidised. This indicates that the
      resupply of electrons from the intersystem chain is relatively more restricted
      under conditions of Ci limitation than is the availability of PS 1 electron
      acceptors. It is proposed that the accumulated Ci pool can directly stimulate the
      ability of O2 to act as a PS 1 acceptor and that the ability of PS 1 acceptors,
      such as O2, to relieve restrictions on intersystem electron transfer is perhaps a
      result of a reduction in cyclic electron flow and a subsequent increase in the
      oxidation state of the plastoquinone pool. 

PMID- 24317800
TI  - Carotenoid triplet state formation in Rhodobacter sphaeroides R-26 reaction
      centers exchanged with modified bacteriochlorophyll pigments and reconstituted
      with spheroidene.
AB  - Triplet state electron paramagnetic resonance (EPR) experiments have been carried
      out at X-band on Rb. sphaeroides R-26 reaction centers that have been
      reconstituted with the carotenoid, spheroidene, and exchanged with 13(2)-OH-Zn
      bacteriochlorophyll a and [3-vinyl]-13(2)-OH-bacteriochlorophyll a at the
      monomeric, 'accessory' bacteriochlorophyll sites BA,B or with pheophytin a at the
      bacteriopheophytin sites HA,B. The primary donor and carotenoid triplet state EPR
      signals in the temperature range 95-150 K are compared and contrasted with those
      from native Rb. sphaeroides wild type and Rb. sphaeroides R-26 reaction centers
      reconstituted with spheroidene. The temperature dependencies of the EPR signals
      are strikingly different for the various samples. The data prove that triplet
      energy transfer from the primary donor to the carotenoid is mediated by the
      monomeric, BChlB molecule. Furthermore, the data show that triplet energy
      transfer from the primary donor to the carotenoid is an activated process, the
      efficiency of which correlates with the estimated triplet state energies of the
      modified pigments. 

PMID- 24317801
TI  - Events near the reaction center in O2 evolving PS II enriched thylakoid
      membranes: The presence of an electric field during the S2 state in a population
      of centers.
AB  - Flash-induced absorption changes at 515 nm observed as a function of flash number
      are examined in relation to the flash-induced fluorescence yields in inside-out
      thylakoids. After partial dissipation of the delocalized transmembrane electric
      field by adding gramicidin, the analysis of period 4 oscillations and of the
      kinetics in the 10 ms-1 s range suggest that the variation of the absorption
      changes at 515 nm as a function of flash number is the result of at least two
      processes:1) an electric field increase related to the S2 state and 2) the fact
      that the field generated by the water protons inside the membrane decreases when
      these protons are released outside the membrane. The former field correlates with
      the flash-induced fluorescence yield increase induced by the donor side of
      Photosystem II. Both measurements show similar oscillations as a function of
      flash number, with maxima on the 1st, 5th and 9th flash. These oscillations,
      after a shift of two flashes, appear to be different from those of the O2 yield
      observed under similar conditions. It is proposed that, in a population of
      centers the electric field during the S2 state reflects the presence of a
      stabilized positive equivalent in the protein close to the Mn complex. 

PMID- 24317802
TI  - The 28 kDa apoprotein of CP 26 in PS II binds copper.
AB  - Photosystem II (PS II) particles isolated from spinach in the presence of 10 MUM
      CuSO4 contained 1.2 copper/300 Chl that was resistant to EDTA. When CuSO4 was not
      added during the isolation, PS II particles contained variable amounts of copper
      resistant to EDTA (0.1-1.1 copper/300 Chl). No correlation was found between
      copper content and oxygen evolving capacity of the PS II particles. To identify
      the copper binding protein, we developed a fractionation procedure which included
      solubilisation of PS II particles followed by precipitation with polyethylene
      glycol. A 22-fold purification of copper with respect to protein was achieved for
      a 28 kDa protein. Partial amino acid sequence of a 13 kDa fragment, obtained
      after V8 (endo Glu-C) protease treatment, showed identity with CP 26 over a 14
      amino acid stretch. EPR measurements on the purified protein suggest oxygen
      and/or nitrogen as ligands for copper but tend to exclude sulfur. We conclude
      that the 28 kDa apoprotein of CP 26 from spinach binds one copper per molecule of
      CP 26. A possible function for this copper protein in the xanthophyll cycle is
      discussed. 

PMID- 24317803
TI  - Characterization of a non-detergent PS II-cytochrome b/f preparation (BS).
AB  - A non-detergent photosystem II preparation, named BS, has been characterized by
      countercurrent distribution, light saturation curves, absorption spectra and
      fluorescence at room and at low temperature (-196 degrees C). The BS fraction is
      prepared by a sonication-phase partitioning procedure (Svensson P and Albertsson
      P-A, Photosynth Res 20: 249-259, 1989) which removes the stroma lamellae and the
      margins from the grana and leaves the appressed partition region intact in the
      form of vesicles. These are closed structures of inside-out conformation. They
      have a chlorophyll a/b ratio of 1.8-2.0, have a high oxygen evolving capacity
      (295 MUmol O2 per mg chl h), are depleted in P700 and enriched in the cytochrome
      b/f complex. They have about 2 Photosystem II reaction centers per 1 cytochrome
      b/f complex.The plastoquinone pool available for PS II in the BS vesicles is 6-7
      quinones per reaction center, about the same as for the whole thylakoid. It is
      concluded, therefore, that the plastoquinone of the stroma lamellae is not
      available to the PS II in the grana and that plastoquinone does not act as a long
      range electron transport shuttler between the grana and stroma lamellae.Compared
      with Photosystem II particles prepared by detergent (Triton X-100) treatment, the
      BS vesicles retain more cytochrome b/f complex and are more homogenous in their
      surface properties, as revealed by countercurrent distribution, and they have a
      more efficient energy transfer from the antenna pigments to the reaction center. 

PMID- 24317804
TI  - Patients leaving the emergency department without being seen by a physician: a
      retrospective database analysis.
AB  - QUESTIONS UNDER STUDY: To describe characteristics of patients leaving the
      emergency department (ED) before being seen by a physician and to identify
      factors associated with a greater risk of leaving the ED too early. METHODS: 
      DESIGN: retrospective database analysis. SETTING: emergency department (ED) of an
      urban teaching hospital admitting 60,000 patients per year. STUDY SUBJECTS: all
      patients older than 18 years admitted to the ED over one year. Collected data:
      patient's and ED visit characteristics. RESULTS: Among the 57,645 patients
      admitted, we identified 2,413 patients (4.2%) who left without being seen (LWBS).
      LWBS patients were more likely to be male (odds ratio [OR] 1.13, 95% confidence
      interval [CI 95%]: 1.03-1.23), single (OR 1.12, CI 95%: 1.01-1.23), unemployed
      (OR 1.27, CI 95%: 1.13-1.44), dependent on welfare (OR 1.29, CI 95%: 1.12-1.50)
      or Muslim (OR 1.19, CI 95%: 1.00-1.42). LWBS patients were also more likely to
      present with less acute emergency triage levels. As complaints, alcohol and/or
      other substance abuse (OR 6.08, CI 95%: 5.04-7.34), neurological problems (OR
      2.23, CI 95%: 1.88-2.64) or dermatological problems (OR 1.63, CI 95%: 1.37-1.94)
      were over-represented in this population. Patients admitted at week-ends (OR
      1.27, 95% CI: 1.16-1.39) and/or during the night (OR = 2.67, 95% C: 2.35-3.02)
      also were at higher risk of leaving the ED prematurely. CONCLUSIONS: LWBS
      patients share some characteristics and a better understanding of these
      characteristics as well as time and logistic issues could ease to implement
      strategies to reduce premature leaving from the ED.

PMID- 24317806
TI  - Linear differentiation of cereal chromosomes : II. Polyploid wheats.
AB  - The BSG test was used in a comparative study of the linear chromosome
      differentiation and the idiograms of T. Macha ssp. tubalicum v. 'letschchumicum '
      Dek. et Men., T. georgicum Dek., T. timopheevi. Zhuk., T. carthlicum Nevski, T.
      dicoccum Schrank, v. 'rufum', T. durum Desf. v. 'Arnautka' were compiled.The
      karyotype of each polyploid wheat species consists of two groups of chromosomes.
      The first is formed by ten pairs of "constant" chromosomes occurring almost in
      all species and the second by all the rest of the "variable" chromosomes that are
      either fully specific for the species in question or occur only in a few species.
      T. timopheevi largely differs from other species of polyploid wheats in the high
      level and specific localization of structural heterochromatin on chromosomes. The
      rols of introgression in wheat evolution and the necessity of establishing a
      General Cytological Nomenclature of Cereal Chromosomes are discussed. 

PMID- 24317805
TI  - Raftlin: a new biomarker in human sepsis.
AB  - Raftlin is a major protein in lipid raft. The aim of this study was to evaluate
      blood levels of raftlin in septic patients. A prospective study of 82 patients
      with sepsis was conducted. Human umbilical vein endothelial cells (HUVECs) or
      mice were exposed to lipopolysaccharide (LPS, 100 ng/ml to HUVECs or 10 mg/kg to
      mice) or subjected to cecal ligation and puncture (CLP) surgery. Data showed that
      LPS induced upregulation of the synthesis and secretion of raftlin in LPS-treated
      HUVECs, and LPS-injected and CLP-mice. In patients admitted to the intensive care
      unit with sepsis, circulating levels of raftlin were significantly elevated,
      compared with control donors. Raftlin levels were higher in patients with septic
      shock, 891.6 (789.7-1,087.8, n = 30) than in patients with severe sepsis, 681.6
      (480.1-819.6, n = 22) or sepsis, 496.1 (418.1-738.9, n = 30), compared with
      healthy volunteers 364.9 (312.1-392.4, n = 21). These results suggest that in
      septic patients, raftlin blood level is related to the severity of sepsis and the
      outcome of the patient and may represent a novel marker of endothelial cell
      dysfunction, and that raftlin can be used as a biomarker for determining the
      severity of sepsis. 

PMID- 24317807
TI  - Male gametophyte in maize: II. Pollen vigor in inbred plants.
AB  - The competitive ability of pollen from inbred plants in mixed pollinations in
      this study is not merely maintained but enhanced through successive generations
      of selfing. The data presented suggest two conclusions: 1) the possible existence
      of pollen-stylar interactions during successive selfings, which select for
      certain pollen genotypes, those best suited for rapid growth through "self"
      styles; and 2) the presence of sporophytic vigor in the heterotic F1 sporophyte,
      or its absence in the "depressed" F7 sporophyte, is not necessarily demonstrated
      in the gametophytic generation, perhaps because it can be overwhelmed by other
      factors, e.g. gametophytic response to selection. 

PMID- 24317794
TI  - Common variation at PPARGC1A/B and change in body composition and metabolic
      traits following preventive interventions: the Diabetes Prevention Program.
AB  - AIMS/HYPOTHESIS: PPARGC1A and PPARGCB encode transcriptional coactivators that
      regulate numerous metabolic processes. We tested associations and treatment (i.e.
      metformin or lifestyle modification) interactions with metabolic traits in the
      Diabetes Prevention Program, a randomised controlled trial in persons at high
      risk of type 2 diabetes. METHODS: We used Tagger software to select 75 PPARGCA1
      and 94 PPARGC1B tag single-nucleotide polymorphisms (SNPs) for analysis. These
      SNPs were tested for associations with relevant cardiometabolic quantitative
      traits using generalised linear models. Aggregate genetic effects were tested
      using the sequence kernel association test. RESULTS: In aggregate, PPARGC1A
      variation was strongly associated with baseline triacylglycerol concentrations (p
      = 2.9 * 10(-30)), BMI (p = 2.0 * 10(-5)) and visceral adiposity (p = 1.9 * 10(
      4)), as well as with changes in triacylglycerol concentrations (p = 1.7 * 10(-5))
      and BMI (p = 9.9 * 10(-5)) from baseline to 1 year. PPARGC1B variation was only
      associated with baseline subcutaneous adiposity (p = 0.01). In individual SNP
      analyses, Gly482Ser (rs8192678, PPARGC1A) was associated with accumulation of
      subcutaneous adiposity and worsening insulin resistance at 1 year (both p <
      0.05), while rs2970852 (PPARGC1A) modified the effects of metformin on
      triacylglycerol levels (p(interaction) = 0.04). CONCLUSIONS/INTERPRETATION: These
      findings provide several novel and other confirmatory insights into the role of
      PPARGC1A variation with respect to diabetes-related metabolic traits. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00004992.

PMID- 24317808
TI  - Sampling strategies for using female gametophytes to estimate heterozygosity in
      conifers.
AB  - Unbiased estimators of genotype and allele frequencies and their respective
      variances are obtained for loci identified by mendelian segregation in haploid
      female gametophytes from individual trees. By a minimum sampling variance
      criterion, the allocation of experimental effort between the number of female
      gametophytes analysed per tree and the number of trees sampled per population is
      examined for a fixed total amount of experimental effort. For estimating
      heterozygosity, the optimum sampling design for many (generally most) cases is
      three female gametophytes per tree, but may be more than three depending upon the
      true genotype frequencies in the population. For estimating allele frequencies,
      the optimum sampling design is one female gametophyte per tree except in cases
      where a strong negative correlation exists between alleles within genotpyes.
      Guidelines are discussed for determining a suitable number of female gametophytes
      to be analysed per tree in order to estimate heterozygosity. 

PMID- 24317809
TI  - Differential response to irradiation in offspring of freshwater and seawater
      substrains of Poecilia (Lebistes) reticulata peters in the "guppy male courtship
      activity test".
AB  - An inbred strain ("Istanbul") of guppies was divided into two substrains, one of
      which was maintained and bred in seawater. The offspring of irradiated animals of
      both substrains (1000 R X-rays to spermatogonia and oogonia of neonatal fish)
      were tested in a new "gruppy male courtship activity test" and compared with
      control groups. The postirradiation response in the seawater substrain was more
      intense than in the freshwater substrain. 

PMID- 24317810
TI  - Effect of test environment on expression of clines and on delimitation of seed
      zones in Douglas-fir.
AB  - Clinal models of population structure in an indigenous tree species can be used
      to delineate seedcollection zones and breeding zones, and to devise transfer
      rules. Models may be developed by growing populations in test environments;
      however, a clinal description may be a function of test environments as well as
      of population genotypes. This possibility was studied by growing seedlings from
      40 populations of northwestern U.S. Douglas-fir (Pseudotsuga menziesii var.
      'menziesii' [Mirb.] Franco) in eight nursery-bed treatments which contrasted air
      and soil temperatures and nutrition. Growth traits measured were stem diameter,
      top height, and dry weight; phenological traits were bud-burst and bud-set dates,
      extension period, and extension period midpoint. Population samples interacted
      significantly with soil temperature for growth traits, and with soil and air
      temperatures combined for phenological traits. Interactions were at least partly
      explained by complex clinal associations of seedling performance with elevation,
      with latitude, and with distance from the ocean of the populations sampled. Both
      the complexity and the gradient of the clinal pattern depended on the trait and
      on the specific test environment.The clinal patterns of greatest complexity were
      expressed in warm air and soil treatments. Dry top-weights of population samples
      were associated with latitudes for samples grown in warm soils, but this
      relationship was not apparent in cool soils. A discrepancy in bud-burst dates
      between extreme coastal and more inland populations was greatest in warm soil
      warm air treatments and was negligible in cool soil-cool air treatments.
      Populations X temperature interactions were attributed to the differential
      response of population samples to spring temperature and photoperiod. It is
      proposed that first attempts at devising a model can be based on nursery or
      growthchamber tests, and that test environments should stress contrasting photo-
      and temperature-regimes.The estimate of clinal structure in Douglas-fir suggests
      that there is more risk within northwestern U.S. in moving provenances east-west
      than north-south, that this risk increases with elevation of provenances, and
      that north-south transfers are more critical near the coast than inland. 

PMID- 24317811
TI  - Flavonoid genetics of the 28-chromosome "Siberian" Iris.
AB  - A Chromatographic survey of flavonoids in the various flower color mutants of the
      28-chromosome "Siberian" Iris (series Sibiricae subseries Sibiricae) was
      conducted using mutants of known genotype (Vaughn 1974). Mutants at the C locus
      contain the malvidin glycoside ensatin, indicating that this gene locus may
      control methylation of delphinidin. Clear white, a mutation at the W locus,
      results in the production of flavones in excess. 

PMID- 24317812
TI  - Direct and maternal genetic effects on body weight maturing patterns in mice.
AB  - Direct and maternal genetic effects were evaluated for maturing patterns of body
      weight in mice using a crossfostering design. Crossfostering was performed in one
      group using dams from populations selected for rapid growth rate (M16 and H6) and
      their reciprocal F1. crosses. A second crossfostering group consisted of dams
      from the respective control populations (ICR and C2) and their reciprocal F1. 's.
      Population differences were partitioned into direct and maternal effects due to
      genetic origin, correlated selection responses, heterosis and cytoplasmic or sex
      linked effects. Degree of maturity was calculated at birth, 12, 21, 31 and 42
      days of age by dividing body weight at each age by 63-day weight. Absolute and
      relative maturing rates were calculated in adjacent age intervals between birth
      and 63 days. Genetic origin effects (ICR vs. C2; M16 vs. H6) were significant for
      many maturity traits, with average direct being more important than average
      maternal genetic effects. In general, correlated responses to selection for
      maturity traits were larger in the M16 population (M16 vs. ICR) than in the H6
      population (H6 vs. C2) and correlated responses in average direct effects were
      larger than average maternal effects. Positive correlated responses in average
      direct effects were found for relative maturing rates at all ages and for
      absolute maturing rates from 31 to 63 days. Apparent correlated responses in
      degree of maturity were negative for M16 and H6. However, further analysis
      suggested that the correlated response for degree of maturity in H6 may be
      positive at later ages and negative at earlier ages. Direct and maternal
      heterosis for degree of maturity was positive in the selected and control
      crosses. Absolute and relative maturing rates showed positive heterosis
      initially, followed by negative heterosis. Reciprocal differences due to the
      cytoplasm or sex-linkage were not important for patterns of maturity. 

PMID- 24317813
TI  - Appendicitis as the presenting manifestation of Kawasaki disease.
AB  - In cases of Kawasaki's disease (KD) presenting as acute surgical abdomen, rarely
      has the presence of acute appendicitis been found. We report two cases of
      histologically confirmed acute appendicitis in the presence of KD and a review of
      the literature as it pertains to acute abdomen and atypical presentations of KD. 

PMID- 24317814
TI  - MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61.
AB  - Increasing evidence indicates that microRNAs (miRNAs) participate in almost every
      step of cellular processes and are often aberrantly expressed in human cancer.
      Therefore, the discovery of miRNAs may provide a new and powerful tool for
      understanding the mechanism and treatment of carcinogenesis. The aim of this
      study was to investigate the functional significance of miR-100 and to identify
      its possible target genes in osteosarcoma (OS) cells. Here, we found that
      expression level of miR-100 was significantly decreased in osteosarcoma tissues
      in comparison with the adjacent normal tissues. The enforced expression of miR
      100 was able to inhibit cell proliferation in Saos-2 and MG63 cells, while its
      antisense oligonucleotides (antisense miR-100) promoted cell proliferation.
      Moreover, our results further revealed that expression of Cyr61, an extracellular
      matrix-associated growth factor, was negatively regulated by miR-100. Therefore,
      we consider that miR-100 acts as a tumor suppressor for osteosarcoma. It may
      provide novel diagnostic and therapeutic options for human osteosarcoma in the
      future. 

PMID- 24317815
TI  - The association between cytotoxic T lymphocyte-associated antigen-4 and cervical
      cancer.
AB  - Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms have been
      associated with many autoimmune diseases and malignancy susceptibility, but the
      relationship between CTLA-4 and cervical cancer is still controversial. Hence, a
      meta-analysis of the published studies for the CTLA-4 gene polymorphisms and the
      risk of cervical cancer was performed to evaluate the association between them.
      Odds ratios (ORs) and 95% confidence intervals (CIs) for the codominant,
      dominant, and recessive genetic models were assessed. The fixed or random effect
      pooled measure was selected on the basis of the heterogeneity test among studies.
      The heterogeneity among studies was evaluated using the I (2). Eight studies with
      2,835 cases and 2,560 controls were included. In seven studies for the CTLA-4
      +49A/G polymorphism, a significant association was showed between the A allele
      and the increased risk of cervical cancer in the codominant (OR 1.16, 95% CI 1.05
      1.29), dominant (OR 1.18, 95% CI 1.03-1.36), and recessive (OR 1.24, 95% CI 1.05
      1.56) models. In five studies for the CTLA-4 -318C/T polymorphism, the meta
      analysis showed a significant association of the C allele with the reduced risk
      of cervical cancer in the codominant (OR 0.79, 95% CI 0.66-0.94) and recessive
      (OR 0.76, 95% CI 0.63-0.93) models. This meta-analysis suggested that +49A/G and 
      318C/T polymorphisms of the CTLA-4 gene were significantly associated with the
      risk of cervical cancer. However, further studies are required to draw a solid
      conclusion on the relation between the CTLA-4 polymorphism and the risk of
      cervical cancer.

PMID- 24317816
TI  - Promoter methylation and immunohistochemical expression of hMLH1 and hMSH2 in
      sporadic colorectal cancer: a study from India.
AB  - To determine the etiological factors of human colorectal cancer (CRC) we assessed
      the frequency and prognostic significance of hMLH1 and hMSH2 genes in conjunction
      with hMLH1 and hMSH2 protein expression in 30 Indian CRC patients. The protein
      expression and promoter methylation of hMLH1 and hMSH2; Mismatch Repair genes
      (MMR) were analyzed by immunohistochemistry and methylation-specific PCR (MSP),
      respectively. A loss of hMLH1 expression was recognized in 4(13.3%) and loss of
      hMSH2 expression was recognized in 2(6.6%) of 30 CRC cases whereas 50% tumors
      showed reduced expression of hMLH1 and 33.3% showed reduced expression of hMSH2
      protein. One tumor showed a loss of both hMLH1 and hMSH2 expression. Normal
      nuclear staining pattern of hMLH1 and hMSH2 was observed in almost all the
      adjoining and normal mucosa. Promoter hypermethylation of the hMLH1 gene was
      detected in 15 of 30 CRC cases (50%) and of hMSH2 gene was only in 3 of 30 CRC
      cases (10%). No promoter methylation of hMLH1 and hMSH2 genes was observed in
      adjoining and normal mucosa. Combination of methylation of hMLH1 and hMSH2 gene
      was observed in two tumors (6.6%). A significant correlation between histological
      grade of the tumor, methylation and expression of hMLH1 gene (p < 0.05) was
      observed. Normal expression of hMLH1 and hMSH2 was seen in all of the
      unmethylated tumors (100%). Nuclear staining and promoter methylation of hMLH1
      and hMSH2 did not significantly influence survival. hMLH1 methylation was common
      and was significantly correlated with loss of hMLH1 protein expression. In
      contrast, hMSH2 methylation was infrequent. These findings suggest that the
      inactivation of MMR gene expression probably via hypermethylation may lead to
      inactivation of their functions which finally leads to tumor aggressiveness and
      the immunostaining of hMLH1 protein can be used as a prognostic factor for
      determining the grade of the tumor.

PMID- 24317817
TI  - Auxin-induced changes in chromosomal protein phosphorylation in wounded potato
      tuber parenchyma.
AB  - White potato tuber tissue reacts upon wounding with a rapid increase in activity
      of both chromatin-bound DNA-dependent RNA polymerase I and II as well as protein
      phosphokinase. This enhancement is more pronounced if 0.1 mM of the synthetic
      auxin 2,4-dichlorophenoxyacetic acid (2,4-D) is added shortly after wounding. The
      effect of the hormone on protein kinases becomes evident only after a lag phase
      of about 10h and lasts throughout the wound-healing period. Different protein
      kinases with different substrate specificity (i.e. histone, phosvitin, casein
      phosphokinases) are distinctly more active in auxin-treated tissues. The
      phosphate is apparently introduced into proteins via seryl and threonyl bonds.
      Acyl or histidyl phosphates are not involved.The properties of protein
      phosphokinases are virtually identical in wounded and auxin-treated tissues.
      However, the pattern of chromosomal proteins and the pattern of their
      phosphorylation in hormone-treated tissues is different from those in wounded
      ones. A drastic stimulation of phosphorylation of both high and low-molecular
      weight chromosomal proteins is characteristic for auxin-treated cells. 

PMID- 24317818
TI  - Post-translational processing of 7S and 11S components of soybean storage
      proteins.
AB  - The synthesis and processing of the major storage proteins in soybean cotyledons
      was studied both in vivo and in vitro. The alpha and alpha' subunits of 7S as
      well as the 11S proteins are synthesized as higher molecular weight-precursors on
      membrane-bound polysomes. The initial translation products of the 7S are
      proteolytically cleaved during translation suggesting the removal of a 'signal
      peptide' as evidenced by the presence of 2alpha and 2alpha' peptides
      immunoreactive with 7S antibody in the in vitro chain completion products of the
      membrane-bound polysomes. This is followed or accompanied by cotranslational
      glycosylation, which increases their size equivalent to that of initially
      synthesized precursors. In vivo pulse-labelled 7S alpha and alpha' products are
      of slightly higher molecular weights than the immunoprecipitable chain-completion
      products, indicating further post-translational modifications. A slow post
      translational processing during a period of 1.5 to 16 h yields the final 7S alpha
      and alpha' glycoproteins.Acidic and basic subunits of the 11S protein appear to
      be synthesized from common large molecular weight (60K-59K) precursors.
      Antibodies to the 11S acidic component recognize both acidic and basic domains in
      the precursor while those raised against basic subunits appear to be specific for
      that region only. The processing of the 11S precursor is also very slow and
      occurs post-translationally. This slow rate of processing, coupled with a
      temporal difference in the synthesis of 7S and 11S components, suggests a highly
      coordinated mechanism for synthesis and packaging of these proteins into protein
      bodies during seed development. 

PMID- 24317819
TI  - Photochrome-mediated regulation of messenger RNAs for the small subunit of
      ribulose 1, 5-bisphosphate carboxylase and the light-harvesting chlorophyll a/b
      protein in Lemna gibba.
AB  - Brief red illumination (10 min/8 hr) of Lemna gibba L. G-3 growing
      heterotrophically in the dark increases the growth of the plants and results in a
      substantial increase in the levels of mRNA for two major chloroplast
      polypeptides. These two nuclear-coded polypeptides are the light-harvesting
      chlorophyll a/b-protein, an intrinsic thylakoid membrane protein, and the small
      subunit of the stromal enzyme ribulose 1, 5-bisphosphate carboxylase [RuP2; 3
      phospho-D-glycerate carboxylyase (dimerizing), E.C.4.1.1.39]. The effect of 10
      min red illumination on the dark growth of the plants is reversed by immediate
      far-red illumination, but the effect on the mRNA levels is not. However, this
      latter response can be reversed by far-red light if the time between the
      beginnings of the red and far-red illumination is reduced to one minute. Thus
      phytochrome is the photoreceptor mediating both responses, and the effect on
      amounts of the translatable mRNAs has a remarkably short escape time.As expected
      from the high level of its mRNA in the plants grown in the dark with intermittent
      red illumination, the small subunit of ribulose 1, 5-bisphosphate carboxylase is
      synthesized in these plants and accumulates without further illumination.
      However, despite the relatively high levels of mRNA for the chl a/b-protein in
      the dark grown plants, this protein does not appear to be synthesized and
      inserted into the thylakoid membranes until the plants are transfered into white
      light. Thus, the normal synthesis of this protein must require light for some
      post-transcriptional process. 

PMID- 24317820
TI  - Fractionation and characterization of polyadenylated RNA from broad bean
      meristematic root cells.
AB  - Several populations of polyadenylated RNA from Vicia faba meristematic root cells
      were fractionated by stepwise thermal elution from poly(U)-Sepharose following
      sequential phenol extraction. Analysis of these fractions showed that the size of
      the poly(A) segment could influence this fractionation, but in some cases other
      characteristics of the molecule are involved. Evidence was obtained that 45-60%
      of the nucleotides of plant polyadenylated RNA are in base paired regions, as was
      previously demonstrated for mammalian mRNA. 

PMID- 24317821
TI  - Clones of cauliflower mosaic virus identified by molecular hybridization in
      turnip leaves.
AB  - Mechanical inoculation of turnip leaves with cauliflower mosaic virus (CaMV)
      results after one to two weeks in the appearance on these leaves of local
      lesions. Local lesions were detected by hybridization of radioactive CaMV DNA
      with nucleic acid immobilized in leaf skeletons by solvent extraction, proteinase
      digestion, and alkali treatment. The pattern of lesions detected as dark circles
      on autoradiographs of the washed leaf skeletons was the same as that detected by
      staining of solvent-extracted leaves for starch. Starch lesions appeared as white
      areas against a dark purple back-ground. These lesions were first detected
      between 5 and 8 days after inoculation and grew in size until 10 days after
      inoculation. Lesions were also detected by staining solvent-extracted and
      proteinase digested leaves with ethidium bromide. The lesions appeared as dark
      areas in a bright fluorescent background, and were found in the same positions as
      the starch lesions. 

PMID- 24317822
TI  - Isolation and characterization of a sequence-specific deoxyriboendonuclease from
      calothrix scopulorum.

PMID- 24317823
TI  - Editorial preface.

PMID- 24317824
TI  - Obituary.

PMID- 24317826
TI  - Evaluation of the role of State transitions in determining the efficiency of
      light utilisation for CO2 assimilation in leaves.
AB  - Wheat leaves were exposed to light treatments that excite preferentially
      Photosystem I (PS I) or Photosystem II (PS II) and induce State 1 or State 2,
      respectively. Simultaneous measurements of CO2 assimilation, chlorophyll
      fluorescence and absorbance at 820 nm were used to estimate the quantum
      efficiencies of CO2 assimilation and PS II and PS I photochemistry during State
      transitions. State transitions were found to be associated with changes in the
      efficiency with which an absorbed photon is transferred to an open PS II reaction
      centre, but did not correlate with changes in the quantum efficiencies of PS II
      photochemistry or CO2 assimilation. Studies of the phosphorylation status of the
      light harvesting chlorophyll protein complex associated with PS II (LHC II) in
      wheat leaves and using chlorina mutants of barley which are deficient in this
      complex demonstrate that the changes in the effective antennae size of
      Photosystem II occurring during State transitions require LHC II and correlate
      with the phosphorylation status of LHC II. However, such correlations were not
      found in maize leaves. It is concluded that State transitions in C3 leaves are
      associated with phosphorylation-induced modifications of the PS II antennae, but
      these changes do not serve to optimise the use of light absorbed by the leaf for
      CO2 assimilation. 

PMID- 24317825
TI  - Cytosolic fructose-1,6-bisphosphatase: A key enzyme in the sucrose biosynthetic
      pathway.
AB  - Fructose-1,6 bisphosphatase (FBPase) is a ubiquitous enzyme controlling a key
      reaction. In non-photosynthetic tissues, it regulates the rate of
      gluconeogenesis. In photosynthetic tissues, two FBPase isozymes (chloroplastic
      and cytosolic) play key roles in carbon assimilation and metabolism. The
      cytosolic FBPase is one of the regulatory enzymes in the sucrose biosynthetic
      pathway - its activity is regulated by both fine and coarse control mechanisms.
      Kinetic and allosteric properties of the plant cytosolic FBPase are remarkably
      similar to the mammalian and yeast FBPase, but differ greatly from those of the
      chloroplastic FBPase. Cytosolic FBPase is relatively conserved among various
      organisms both at amino acid and nucleotide sequence levels. There is slightly
      higher similarity between mammalian FBPase and plant cytosolic FBPase than there
      is between the two plant FBPases. Expression of plant cytosolic FBPase gene is
      developmentally regulated and appears to be coordinated with the expression of
      Rubisco and other carbon metabolism enzymes. Similar to the gluconeogenic FBPase,
      relatively rapid end product repression of FBPase gene occurs in plant. However,
      unlike the gluconeogenic FBPase, a concurrent decline in plant FBPase activity
      does not occur in response to increased end product levels. The physiological
      significance of FBPase gene repression, therefore, remains unclear in plants.
      Both expression and activity of the cytosolic FBPase are regulated by
      environmental factors such as light and drought conditions. Light-dependent
      modulation of FBPase activity in plants appears to involve some type of
      posttranslational modification. In addition to elucidating the exact nature of
      the presumed posttranslational modification, cloning of genomic and upstream
      sequences is needed before we fully understand the molecular regulation of the
      cytosolic FBPase in plants. Use of transgenic plants with altered rates of FBPase
      activity offers potential for enhanced crop productivity. 

PMID- 24317827
TI  - The role of carbon dioxide in light-activated hydrogen production by
      Chlamydomonas reinhardtii.
AB  - Light-activated hydrogen and oxygen evolution as a function of CO2 concentration
      in helium were measured for the unicellular green alga Chlamydomonas reinhardtii.
      The concentrations were 58, 30, 0.8 and 0 ppm CO2. The objective of these
      experiments was to study the differential affinity of CO2/HCO 3 (-) for their
      respective Photosystem II and Calvin cycle binding sites vis-a-vis photoevolution
      of molecular oxygen and the competitive pathways of hydrogen photoevolution and
      CO2 photoassimilation. The maximum rate of hydrogen evolution occurred at 0.8 ppm
      CO2, whereas the maximum rate of oxygen evolution occurred at 58 ppm CO2. The key
      result of this work is that the rate of photosynthetic hydrogen evolution can be
      increased by, at least partially, satisfying the Photosystem II CO2/HCO 3 (-)
      binding site requirement without fully activating the Calvin-Benson CO2 reduction
      pathway. Data are presented which plot the rates of hydrogen and oxygen evolution
      as functions of atmospheric CO2 concentration in helium and light intensity. The
      stoichiometric ratio of hydrogen to oxygen changed from 0.1 at 58 ppm to
      approximately 2.5 at 0.8 ppm. A discussion of partitioning of photosynthetic
      reductant between the hydrogen/hydrogenase and Calvin-Benson cycle pathways is
      presented. 

PMID- 24317828
TI  - Interaction of flavodoxin with cyanobacterial thylakoids.
AB  - Flavodoxin from the cyanobacterium Anabaena PCC 7119 has been shown to mediate,
      under illumination, the transfer of electrons from the thylakoidal membranes that
      were isolated from the same organism, to both the enzyme ferredoxin-NADP(+)
      reductase and cytochrome c. Chemical cross-linking of ferredoxin or flavodoxin to
      the photosynthetic membranes provides a preparation that is active in cytochrome
      c photoreduction without the addition of external protein carrier. NADP(+)
      photoreduction, albeit diminished, was observed only after addition of exogenous
      electron carrier protein. Immunoblotting analysis of the chemical adduct reveals
      that flavodoxin binds to a 10 kDa polypeptide subunit in the cyanobacterial
      Photosystem I which appears to act as its physiological partner in the electron
      transfer process. 

PMID- 24317829
TI  - Seasonal trends in leaf photosynthesis and stomatal conductance of drought
      stressed and nonstressed pearl millet as associated to vapor pressure deficit.
AB  - Single leaf photosynthesis (Pn) and stomatal conductance (Cg) of drought stressed
      and nonstressed pearl millet [Pennisetum americanum (L.) Leeke] were measured
      across growth stages to determine if a pattern exists in Pn and Cg during the
      growing season and to evaluate the influence of air vapor pressure deficit (VPDa)
      on the seasonal variations of Pn and Cg. Leaf photosynthesis and Cg were measured
      independently on pearl millet plants grown at the driest (drought stressed) and
      wettest (nonstressed) ends of a line-source irrigation gradient system. Well
      defined and predictable variations in both Pn and Cg were found across two
      growing seasons. Leaf photosynthesis of the nonstressed plants declined from a
      maximumof 25.8 MUmol m(-2) s(-1) at the flag leaf emergence (48 days after
      planting, DAP) to a minimum of 14.5 MUmol m(-2) s(-1) at physiological maturity.
      Stomatal conductance of the nonstressed plants peaked at the flowering and early
      grain fill stages and declined as plants approached maturity. In contrast, Pn and
      Cg of the stressed plants declined from a maximum at flag leaf emergence to a
      minimum at flowering and increased as plants approached maturity. High VPDa
      during the flowering and grain fill stages induced stomatal closure and decreased
      Pn in the stressed plants. High mid-season VPDa did not induce stomatal closure
      and did not reduce leaf photosynthesis in nonstressed plants. The lack of
      sensitivity of Pn to VPDa in the nonstressed treatment suggests large air VPD
      such as that prevalent in southern Arizona does not limit the growth of irrigated
      pearl millet by limiting CO2 assimilation. 

PMID- 24317830
TI  - Patterns of phosphoenolpyruvate carboxylase activity and cytosolic pH during
      light activation and dark deactivation in C3 and C 4 plants.
AB  - The rate and extent of light activation of PEPC may be used as another criterion
      to distinguish C3 and C4 plants. Light stimulated phosphoenolypyruvate
      carboxylase (PEPC) in leaf discs of C4 plants, the activity being three times
      greater than that in the dark but stimulation of PEPC was limited about 30% over
      the dark-control in C3 species. The light activation of PEPC in leaves of C3
      plants was complete within 10 min, while maximum activation in C4 plants required
      illumination for more than 20 min, indicating that the relative pace of PEPC
      activation was slower in C4 plants than in C3 plants. Similarly, the dark
      deactivation of the enzyme was also slower in leaves of C4 than in C3 species.
      The extent of PEPC stimulation in the alkaline pH range indicated that the dark
      adapted form of the C4 enzyme is very sensitive to changes in pH. The pH of
      cytosol-enriched cell sap extracted from illuminated leaves of C4 plants was more
      alkaline than that of dark-adapted leaves. The extent of such light-dependent
      alkalization of cell sap was three times higher in C4 leaves than in C3 plants.
      The course of light-induced alkalization and dark-acidification of cytosol
      enriched cell sap was markedly similar to the pattern of light activation and
      dark-deactivation of PEPC in Alternanthera pungens, a C4 plant. Our report
      provides preliminary evidence that the photoactivation of PEPC in C4 plants may
      be mediated at least partially by the modulation of cytosolic pH. 

PMID- 24317831
TI  - Novel characteristics of cassava, Manihot esculenta Crantz, a reputed C3-C 4
      intermediate photosynthesis species.
AB  - The cassava plant, Manihot esculenta, grows exceptionally well in low fertility
      and drought prone environments, but the mechanisms that allow this growth are
      unknown. Earlier, and sometimes contradictory, work speculated about the presence
      of a C4-type photosynthesis in cassava leaves. In the present work we found no
      evidence for a C4 metabolism in mature attached cassava leaves as indicated i) by
      the low, 2 to 8%, incorporation of (14)CO2 into C4 organic acids in short time
      periods, 10 s, and the lack of (14)C transfer from C4 acids to other compounds in
      (12)CO2, ii) by the lack of C4 enzyme activity changes during leaf development
      and the inability to detect C4 acid decarboxylases, and iii) by leaf CO2
      compensation values between 49 and 65 MUl of CO2 1(-1) and by other infrared gas
      exchange photosynthetic measurements. It is concluded that the leaf biochemistry
      of cassava follows the C3 pathway of photosynthesis with no indication of a C3-C4
      mechanism.However, cassava leaves exhibit several novel characteristics. Attached
      leaves have the ability to effectively partition carbon into sucrose with nearly
      45% of the label in sucrose in about one min of (14)CO2 photosynthesis,
      contrasting with 34% in soybean (C3) and 25% in pigweed (C4). Cassava leaves
      displayed a strong preference for the synthesis of sucrose versus starch. Field
      grown cassava leaves exhibited high rates of photosynthesis and curvilinear
      responses to increasing sunlight irradiances with a tendency to saturate only at
      high irradiances, above 1500 MUmol m(-2) s(-1). Morphologically, the cassava leaf
      has papillose epidermal cells on its lower mesophyll surface that form 'fence
      like' arrangements encircling guard cells. It is proposed that the active
      synthesis of sugars has osmotic functions in the cassava plant and that the
      papillose epidermal cells function to maintain a healthy leaf water status in
      various environments. 

PMID- 24317832
TI  - Low molecular weight subunits associated with the cytochrome b 6 f complexes from
      spinach and Chlamydomonas reinhardtii.
AB  - Cytochrome b 6 f complexes, prepared from spinach and Chlamydomonas thylakoids,
      have been examined for their content of low molecular weight subunits. The
      spinach complex contains two prominent low molecular weight subunits of 3.7 and
      4.1 kD while a single prominent component of 4.5 kD was present in the
      Chlamydomonas complex. An estimation of the relative stoichiometry of these
      subunits suggests several are present at levels approximating one copy per
      cytochrome complex. The low molecular weight subunits were purified by reversed
      phase HPLC and N-terminal sequences obtained. Both the spinach and Chlamydomonas
      cytochrome complexes contain a subunit that is identified as the previously
      characterized petG gene product (4.8 kD in spinach and 4.1 kD in Chlamydomonas).
      A second subunit (3.8 kD in spinach and 3.7 kD in Chlamydomonas) appears to be
      homologous in the two complexes and is likely to be a nuclear gene product. The
      possible presence of other low molecular weight subunits in these complexes is
      also considered. 

PMID- 24317833
TI  - Polyamines in the photosynthetic apparatus : Photosystem II highly resolved
      subcomplexes are enriched in spermine.
AB  - The three main polyamines putrescine (Put), spermidine (Spd) and spermine (Spm)
      were characterized by HPLC in intact spinach leaf cells, intact chloroplasts,
      thylakoid membranes, Photosystem II membranes, the light-harvesting complex and
      the PS II complex. All contain the three polyamines in various ratios; the HPLC
      polyamine profiles of highly resolved PS II species (a Photosystem II core and
      the rection center) suggest an enrichment in the polyamine Spm. 

PMID- 24317834
TI  - Light-independent synthesis of LHC IIb polypeptides and assembly of the major
      pigmented complexes during the initial stages of Pinus palustris seedling
      development.
AB  - Pinus palustris has a greatly reduced need for light to initiate chloroplast
      development in comparison to angiosperms. Light is not required for chlorophyll
      synthesis in dark-grown Pinus palustris seedlings. However, embryos do not
      contain chlorophyll, and synthesis is limited to seedlings having cotyledon
      lengths between about 0.5 cm and 2.0 cm. The final amount of chlorophyll
      accumulated by dark-grown seedlings is about one fifth of that in light-grown
      seedlingsat the same stage. The major light-harvesting chlorophyll a/b
      polypeptides of Photosystem II (LHC IIb) are absent in the embryos but begin to
      accumulate in seedlings of 0.5 cm cotyledon length, irrespective of the light
      conditions. Although dark-grown seedlings accumulate most of the pigmented
      complexes seen in light-grown seedlings, there are differences in the subunit
      structure of some of them. These findings suggest that the majority of the
      components of the photosynthetic membrane do not require light for induction of
      synthesis or assembly into complexes, but that the final forms seen in light
      grown seedlings may require light. 

PMID- 24317835
TI  - Triplet state EPR of reaction centers from the His(L173)->Leu (L173) mutant of
      Rhodobacter sphaeroides which contains a heterodimer primary donor.
AB  - Electron paramagnetic resonance (EPR) spectroscopy has been used to examine the
      triplet states in reaction centers of Rhodobacter sphaeroides which have
      undergone a genetic modification affecting the primary donor. Reaction centers
      containing the His(L173)->Leu(L173) substitution in the amino acid sequence have
      a primary donor which consists of a BChl-BPh heterodimer. The triplets formed in
      this heterodimer reaction center were compared with those formed in the wild-type
      reaction center which contains the BChl-BChl homodimer. Both reaction centers
      transfer triplet energy to the carotenoid under illumination at liquid nitrogen
      temperatures (~90 K). However, the intensity of the carotenoid triplet signal is
      significantly decreased in the Leu(L173) mutant compared with the wild-type
      reaction center. At 12 K, in wild-type reaction centers only the primary donor
      triplet is observed. The Leu(L173) mutant exhibits a signal similar to that
      observed by Bylina et al. (1990) in His(M200)->Leu(M200) mutant reaction centers
      from Rb. capsulatus. The values of the zero-field splitting parameters of this
      triplet are discussed within the context of various models for the primary donor
      triplet state. No alteration in the ability of the carotenoid to quench the
      primary donor triplet state results from mutations at these sites. 

PMID- 24317837
TI  - Corrigendum : volume 36: 111-118, 1993.

PMID- 24317836
TI  - Identification of the subunit carrying FeS-centers A and B in the P840-reaction
      center preparation of Chlorobium limicola.
AB  - The product of the second gene in a transcription unit for the P840-reaction
      center of Chlorobium limicola f.sp. thiosulfatophilum, which codes for a protein
      of 23.87 kDa with 232 amino acids, was identified as the subunit migrating in SDS
      PAGE at the apparent molecular weight of 32 kDa in reaction center preparations,
      by Western blotting and N-terminal sequencing. This protein corresponds to PsaC,
      a 8 kDa-subunit of Photosystem 1 which carries the FeS-centers A and B. 

PMID- 24317838
TI  - Left-ear-driven representational pseudoneglect for mentally represented real-word
      scenes created from aural-verbal description.
AB  - The current research explored pseudoneglect for the mental representation of real
      world scenes generated from aural-verbal description in the complete absence of
      direct visual processing. Healthy participants listened binaurally or monaurally
      to aural-verbal descriptions of novel real-world scenes with familiar landmarks
      (e.g., 'shop', 'cafe', 'school') to be imagined on the left- or right-hand side.
      Participants were asked to mentally represent the street scene using a
      visuospatial template though it was up to participants how they mentally
      represented each individual landmark within the street (i.e., in terms of colour
      and size). There were two main tasks: a relative judgement task (which side of
      the street contains the most landmarks?) and a recall task (recall the landmarks
      on the left vs. right side of the street). When stimuli were presented monaurally
      to the left ear (favouring the activation of the right hemisphere) participants
      demonstrated representational pseudoneglect and showed a bias towards responding
      that there were more landmarks on the left compared to the right. However, this
      did not lead to enhanced recall for left side landmarks. When stimuli were
      presented binaurally or monaurally to the right ear, there was no evidence of
      representational pseudoneglect for the relative judgement or recall task. The
      current study discusses how the use of monaural presentation may boost right
      hemisphere activation in aural-verbal experimental paradigms designed to explore
      representational pseudoneglect.

PMID- 24317839
TI  - Stone-free rate (SFR): a new proposal for defining levels of SFR.
AB  - There is a lack of consensus in the definition of stone-free rate (SFR) after
      ureteric or renal stone surgery. We propose a simple classification to define
      levels of SFR post-treatment. 

PMID- 24317841
TI  - Rorschach differences in normal and delinquent white male adolescents: A
      discriminant function analysis.
AB  - Rorschach productions from 38 normal and 30 delinquent White male adolescents
      were scored by three Ph.D. clinical psychologists according to the method given
      by Beck. The groups were equated for IQ, social class, and age at the time of
      testing. Rorschach scales representative of various personality dimensions,
      i.e.,R, M, F, F+, FC, CF, C, FC: CF + C, Sum C, Affective Ratio, Shading, H,
      andA, were subjected to a linear discriminant analysis. The results showed highly
      significant and accurate differentiation between the groups (p<0.0005, correct
      classification rate =86.8%); however, theAffective Ratio was the only scale that
      heavily contributed to the discrimination. The difference between the groups on
      this scale was attributed to the delinquents' passive cognitive style. The
      results also lend support to the notion that delinquents differ from normals
      along the dimension of impulsivity, a finding relevant to psychodynamic theories
      of delinquency as reflective of serious ego deficits. Fuller consideration of
      Rorschach symbolic content and qualitative features of response is recommended. 

PMID- 24317842
TI  - Alcohol use among college students: Some competing hypotheses.
AB  - This paper presents a longitudinal study of alcohol use among college students.
      Three hypothesized predictors of alcohol use are found to have an independent
      effect when the other predictors and prior drinking are held constant: the
      drinking context of the dormitory living group, informal social involvement in
      college, and lack of commitment to religious and academic values. These
      predictors are also related to the onset of drinking during the freshman year for
      those who entered college as abstainers. The pattern varies somewhat for males
      and females, with the dormitory contextual effect larger for females. Formal
      involvement in college activities and psychological stress have no independent
      effect on drinking. The results are discussed in relation to previous work on
      alcohol use. 

PMID- 24317843
TI  - Sex role and dating orientation.
AB  - The assumption that males approach dating from a pronounced psychobiological
      orientation while females approach it from a psychoaffectional orientation was
      questioned. The sex role adopted by the individual was considered to be as
      important a variable as biological sex. Male and female subjects from three age
      groups, 16-17 years, 19-20 years, and 24-25 years, completed questionnaires
      designed to measure their sex roles and dating orientations. All groups of males
      were found to approach the dating relationship from both a psychoaffectional and
      psychobiological orientation, while all groups of females approached it from a
      psychoaffectional orientation and showed an increase in psychobiological
      orientation with increasing age and increasing depth of relationship. Significant
      differences were also found in dating attitudes between male and female subjects
      adopting different sex roles. It was concluded that neither masculinity and
      femininity, nor psychobiological and psychoaffectional attitudes to dating, lie
      on single continua. Masculine and feminine sex roles as independent dimensions
      influence psychobiological and psychoaffectional orientations to dating which are
      in themselves independent dimensions and not ends of a single continuum. 

PMID- 24317844
TI  - The impact of divorce and subsequent father absence on children's and
      adolescents' self-concepts.
AB  - The self-concepts of 406 grade school and junior high school students were
      assessed in this study. It was found that children and adolescents who had
      experienced father loss through divorce and whose mothers hadnot remarried
      demonstrated significantly lower self-concepts than those who were from intact
      families. Interestingly, children and adolescents who had experienced father loss
      through divorce and whose mothers had remarried were found to possess lower self
      concepts than those from intact families, but this difference was not
      statistically significant. These findings were found across grade levels (i.e.,
      grades 3-8) and for both sexes. The importance of these findings are discussed in
      light of current trends toward an increasing divorce rate and an increasing
      presence of stepfathers in American families. 

PMID- 24317845
TI  - The relation between the ethics of personal conscience-social responsibility and
      principled moral reasoning.
AB  - Three samples of college students were tested on Hogan's Survey of Ethical
      Attitudes (SEA) and Rest's Defining Issues Test (DIT), a test of moral reasoning
      ability in the Kohlbergian tradition. In addition, one of the samples took
      Collins's revision of Rotter's Internal-External Scale (I-E) while another sample
      took Snyder's Self-Monitoring Scale. There was a small but reliable tendency for
      subjects who endorsed the "ethics of personal conscience," as measured by the
      SEA, to show greater maturity in moral reasoning, as assessed by the DIT. This
      result was seen as raising some interesting questions about the relation between
      liberalism-conservatism and moral maturity. The subjects who advocated the ethics
      of social responsibility tended to show more internal locus of control as
      measured by the I-E scale. There also was a tendency for subjects who preferred
      the morality of conventional role-conformity, as measured by the DIT, to have
      high scores on the Self-Monitoring Scale. The correlations between personal
      conscience and mature moral reasoning, while significant, were small enough to
      make it seem that people of various social and political attitudes are likely to
      achieve maturity in moral reasoning. 

PMID- 24317846
TI  - Adolescents' concepts of marriage: A structural-developmental analysis.
AB  - This study involved the construction of a theory and scoring manual for assessing
      the developmental stages of individuals' concepts of marriage. Four stages
      (Magical, Idealized Conventional, Individualistic, Affirmational) were
      identified. The reliability of the scoring procedure (interrater and item-total
      protocol) was judged to be acceptable. Correlations with age, schooling, ego
      development, and years of marriage support the marriage concepts stage sequence.
      Adolescents (N=162) scored at the first two stages of marriage concepts. However,
      in ego development, their mean score was above the Conformist level, thus
      suggesting that the adolescents were more advanced in their overall personality
      development than in their developmental stages of marriage concepts. 

PMID- 24317847
TI  - Problem boys in young adulthood: Teachers' ratings and twelve-year follow-up.
AB  - In an earlier paper we reported that teachers' ratings of child guidance clinic
      children were associated with the children's global adjustment in young
      adulthood. Teachers' ratings, especially the peer relations measure, far
      surpassed other data sources in predicting general adult mental status. Other
      sources were developmental history, social history, family information, and
      psychiatric and psychological evaluations. The purposes of the present
      investigation were to evaluate mother-son reliability on adulthood information,
      and to determine whether teacher-rated behaviors of clinic boys predicted
      specific adult behaviors or were only globally related. Interviewed separately
      when sons were young adults, mothers and sons closely agreed on sons' adult
      behavior, with mothers somewhat underreporting sons' negative behaviors. The
      major finding was that one teacher-rated item,fails to get along with other
      children, was closely associated with a wide spectrum of adult behaviors. This
      was not due to the peer relations indicator serving as a global statistic
      reflecting general childhood impairment. It was also found that composite scores
      of childhood and adulthood bad conduct were significantly related to each other. 

PMID- 24317848
TI  - Clinical efficacy of adjunctive G-CSF on solid tumor and lymphoma patients with
      established febrile neutropenia.
AB  - BACKGROUND: The use of granulocyte colony-stimulating factor (G-CSF) as a
      prophylaxis against febrile neutropenia (FN) is well documented in the
      literature; however, the therapeutic use of G-CSF in the treatment of FN remains
      controversial. This study assessed the efficacy of adjunctive G-CSF in the
      treatment of FN by evaluating clinical outcomes. METHODS: This was a single
      center, prospective cohort study conducted at the National Cancer Center in
      Singapore. Adult patients who had received chemotherapy and developed FN between
      January 2009 and January 2012 were included in the analysis. The clinical
      efficacy of adjunctive G-CSF was evaluated by investigating the duration of
      hospitalization, duration to absolute neutrophil count (ANC) recovery, duration
      of grade IV neutropenia, duration to fever resolution, duration of antibiotic
      therapy, and incidence of documented infections. A multivariate analysis was
      performed to identify patients who could potentially benefit from adjunctive G
      CSF. RESULTS: Four hundred and thirty patients were analyzed. Majority manifested
      low-risk FN (81.2%) based on the Multinational Association of Supportive Care in
      Cancer (MASCC) scoring. Compared to patients who did not receive adjunctive G
      CSF, patients receiving adjunctive G-CSF had a nonsignificant reduction in the
      duration of hospitalization (3.5 vs. 3.7 days, p = 0.41) and in ANC recovery time
      (3.4 vs. 3.5 days, p = 0.76). Neutropenia-related mortality was lower among those
      who have received adjunctive G-CSF (2.4 vs. 8.4%, p = 0.006). Patients of Indian
      ethnicity and those who underwent gemcitabine-containing chemotherapy were less
      likely to receive adjunctive G-CSF treatment. CONCLUSIONS: This observational
      study suggested that adjunctive G-CSF may confer clinical benefits among solid
      tumor and lymphoma patients with established febrile neutropenia. Further
      research should be conducted to validate the findings.

PMID- 24317850
TI  - Preferences for aggressive care in underserved populations with advanced-stage
      lung cancer: looking beyond race and resuscitation.
AB  - PURPOSE: This paper examines the relationship between race, religiousness,
      spiritual well-being, antitumor treatment and preference for aggressive care
      among Black and White patients with advanced stage lung cancer receiving
      ambulatory cancer care in an urban setting. METHODS: A cross-sectional
      exploration of patients enrolled in a Cleveland-based longitudinal study after
      initial diagnosis of advanced lung cancer were interviewed in Cleveland regarding
      religiousness, spiritual well-being, preferences for cardiopulmonary
      resuscitation (CPR), goals of aggressive care, and willingness to tolerate
      adverse health states. Receipt of antitumor treatment was identified from medical
      records. RESULTS: We analyzed data from 67 Black and 129 White patients (N=196).
      Regression analysis for CPR showed that race was not associated with preference
      for CPR (OR=1.12, CI 0.44-2.85). The odds of choosing CPR were three times higher
      among patients receiving antitumor treatment (OR=3.26, CI 1.12-9.44). Greater
      willingness to endure adverse health states was associated with higher spiritual
      well-being scores (b=0.12, CI 0.01-0.25). Choosing goals to extend life versus
      relieve pain was higher among persons with higher spiritual well-being as well
      (RRR=1.08, CI 1.01-1.16), yet the relationship with religiousness was negative
      (RRR=0.46, CI 0.22-0.98). CONCLUSIONS: After controlling for multiple factors,
      race was associated only with CPR, but not with other measures of preference for
      aggressive care. In addition, receipt of active antitumor treatment was
      positively associated with preference for CPR and spiritual well-being was
      important to setting end-of-life care goals and perspectives. Future directions
      for tailoring end-of-life care decision-making initiatives should move beyond
      race and discussions of CPR alone and focus on a full spectrum of patient beliefs
      and preferences at the end of life.

PMID- 24317849
TI  - Palonosetron and dexamethasone for the prevention of nausea and vomiting in
      patients receiving allogeneic hematopoietic stem cell transplantation.
AB  - PURPOSE: The primary aim of this study was to evaluate the efficacy of
      palonosetron combined with dexamethasone in the prevention of vomiting, and
      especially nausea, in patients receiving allogeneic stem cell transplantation.
      METHODS: Palonosetron 0.25 mg was given to 27 patients receiving allogeneic
      transplantation on the first day of conditioning, and then every other day during
      the entire conditioning period. Dexamethasone was given daily also during
      conditioning. Vomiting and nausea were recorded daily according to CTCAE version
      4.0 from the start of conditioning to Day 7 after transplantation. In addition,
      MASCC antiemetic tool (MAT) was also used in parallel to evaluate the intensity
      of nausea. RESULTS: The treatment was well tolerated; 25.9 and 40.7 % of the
      patients had grade 2/3 vomiting and nausea respectively during conditioning. The
      incidences of grade 2/3 vomiting and nausea were even higher in the first week
      after transplantation (40.7 and 51.8 %, respectively). The score of MAT
      correlated well with the grade of CTCAE. However, the difference in the mean
      intensity of nausea between period of conditioning and the first week after HSCT
      was significant only by using MAT (0.96 +/- 1.829 vs. 3.81 +/- 3.386, p=0.001)
      but not CTCAE (1.26   +/- 0.903 vs. 1.63 +/-0.967, p=0.152). CONCLUSION:
      Palonosetron combined with dexamethasone is effective in preventing vomiting
      during conditioning. However, more effort should be made to alleviate nausea
      during conditioning and both nausea and vomiting in the first week after
      transplantation. Furthermore, MAT has a higher discriminant power than CTCAE in
      assessing the intensity of nausea in patients receiving allogeneic
      transplantation.

PMID- 24317851
TI  - Physical exercise and therapy in terminally ill cancer patients: a retrospective
      feasibility analysis.
AB  - PURPOSE: Physical exercise (PE) and/or therapy (PT) shows beneficial effects in
      advanced cancer patients and is increasingly implemented in hospice and
      palliative care, although systematic data are rare. This retrospective study
      systematically evaluated the feasibility of PE/PT in terminally ill cancer
      patients and of different modalities in correspondence to socio-demographic and
      disease- and care-related aspects. METHODS: All consecutive terminally ill cancer
      patients treated in a palliative care inpatient ward during a 3.5-year period
      were included. The modalities were chosen according to the therapists' and
      patients' appraisal of current performance status and symptoms. RESULTS: PE/PT
      were offered to 572 terminally ill cancer patients, whereof 528 patients (92 %)
      were able to perform at least one PE/PT unit (average 4.2 units/patient). The
      most frequently feasible modalities were physical exercises in 50 %, relaxation
      therapy in 22 %, breathing training in 10 %, and positioning and lymph edema
      treatment in 6 % each. Physical exercise and positioning treatment were performed
      significantly more often in older patients (p=0.009 and p=0.022, respectively),
      while relaxation (p=0.05) and lymph edema treatment (p=0.001) were used more
      frequently in younger. Breathing training was most frequently performed in head
      and neck cancer (p=0.002) and lung cancer (p=0.026), positioning treatment in
      brain tumor patients (p=0.021), and lymph edema treatment in sarcoma patients
      (p=0.012). CONCLUSIONS: PE/PT were feasible in >90 % of terminally ill cancer
      patients to whom PE/PT had been offered. Physical exercises, relaxation therapy,
      and breathing training were the most frequently applicable methods. Prospective
      trials are needed to evaluate the efficacy of specific PE/PT programs in
      terminally ill cancer patients.

PMID- 24317852
TI  - TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis
      by regulating beta cell mass.
AB  - AIMS/HYPOTHESIS: Common genetic variations of the transcription factor 7-like 2
      gene (encoded by TCF7L2), one of the T cell factor/lymphoid enhancer-binding
      factor transcription factors for the converging wingless-type MMTV integration
      site family (Wnt)/beta-catenin signalling pathway, are known to be associated
      with type 2 diabetes. Individuals with at-risk alleles of TCF7L2 exhibit impaired
      insulin secretion. Although previous studies using animal models have revealed
      the existence of a relationship between the Wnt/beta-catenin signalling pathway
      and glucose homeostasis, it remains unclear whether TCF7L2 in the pancreatic beta
      cells might be causally involved in insulin secretion in vivo. In this study, we
      investigated the role of TCF7L2 expressed in the pancreatic beta cells in glucose
      homeostasis. METHODS: Three independent groups of genetically engineered mice (DN
      mice) were generated, in which expression of the dominant-negative form of Tcf7l2
      was driven under a rat insulin promoter. Phenotypes of both adult and newborn
      mice were evaluated. The levels of genes and proteins expressed in isolated
      islets were determined by reverse transcription-quantitative PCR and western blot
      analysis, respectively. RESULTS: Adult DN mice showed impaired glucose tolerance
      and decreased insulin secretion in both oral and intraperitoneal glucose
      tolerance tests. Marked reduction of the beta cell area and whole-pancreas
      insulin content was observed in both the adult and newborn DN mice. Islets from
      the DN mice showed decreased gene expressions of Ccnd1, Ccnd2, Irs1, Irs2, Ins1,
      Ins2 and Mafa, consistent with the deleterious effects of the dominant-negative
      form of Tcf7l2 on beta cell proliferation and insulin production.
      CONCLUSIONS/INTERPRETATION: TCF7L2 expressed in the pancreatic beta cells plays a
      crucial role in glucose metabolism through regulation of the beta cell mass.

PMID- 24317853
TI  - Ovarian sensitivity index is a better measure of ovarian responsiveness to
      gonadotrophin stimulation than the number of oocytes during in-vitro
      fertilization treatment.
AB  - PURPOSE: To validate the use of the ovarian sensitivity index (OSI) as a measure
      of ovarian response during in-vitro fertilization (IVF) treatment. METHODS: This
      is a retrospective study carried out in an assisted reproduction unit in a
      teaching hospital. We analysed data from 2,556 women undergoing the first IVF
      cycle between 2002 and 2009. OSI was calculated as the number of retrieved
      oocytes divided by total dose of FSH administered (per 1,000 IU). Its correlation
      to other parameters of ovarian response was compared to that of the oocyte
      number. RESULTS: The correlation coefficients of OSI with age, AFC, AMH, total
      dose of gonadotrophin, average daily dose of gonadotrophin and duration of
      stimulation were significantly higher than that of oocyte number with these
      respective parameters. OSI demonstrated a higher intraclass correlation
      coefficient (ICC) than the oocyte number when comparing the two parameters across
      the first and second stimulated IVF cycles. CONCLUSIONS: OSI is a better measure
      of ovarian responsiveness to gonadotrophin stimulation than the oocyte number,
      and is particularly useful when different subjects are treated with different
      stimulation regimens which would have confounding effect on the oocyte number.

PMID- 24317854
TI  - A randomized controlled trial comparing two vitrification methods versus slow
      freezing for cryopreservation of human cleavage stage embryos.
AB  - PURPOSE: To compare two different vitrification methods to slow freezing method
      for cryopreservation of human cleavage stage embryos. DESIGN: Prospective
      randomised trial. SETTING: University assisted reproduction centre. PATIENT(S):
      568 patients (mean age 33.4 +/- 5.2) from April 2009 to April 2011. METHODS: 1798
      supernumerary good-quality cleavage stage embryos in 645 IVF cycles intended to
      be cryopreserved were randomly allocated to three groups: slow freezing,
      vitrification with the Irvine(r) method, vitrification with the Vitrolife(r)
      method. MAIN OUTCOME MEASURE(S): Embryo survival and cleavage rates, implantation
      rate. RESULTS: A total of 1055 embryos were warmed, 836 (79.2%) survived and 676
      were finally transferred (64.1%). Post-warming embryos survival rate was
      significantly higher after vitrification (Irvine: 89.4%; Vitrolife: 87.6%) than
      after slow freezing (63.8%) (p < 0.001). No differences in survival rates were
      observed between the two vitrification methods, but a significant higher cleavage
      rate was observed using Irvine compared to Vitrolife method (p < 0.05).
      Implantation rate (IR) per embryo replaced and per embryo warmed were
      respectively 15.8% (41/259) and 12.4% (41/330) for Irvine, 17.0% (40/235) and
      12.1% (40/330) for Vitrolife, 21.4% (39/182) and 9.9% (39/395) for slow-freezing
      (NS). CONCLUSIONS: Both vitrification methods (Irvine and Vitrolife) are more
      efficient than slow freezing for cryopreservation of human cleavage stage embryos
      in terms of post-warming survival rate. No significant difference in the
      implantation rate was observed between the three cryopreservation methods.

PMID- 24317855
TI  - Phytochrome and internode elongation in Chenopodium polyspermum L. sites of
      photoreception.
AB  - The elongation of the fourth internode of 'fully green' Chenopodium polyspermum
      L. is modulated by far-red light (FR) given in addition to the main light period.
      Two different types of organs are responsible for the photoreception of FR
      producing the end-of-day effect; the stem and the leaves situated just above and
      below the reacting internode. Photoreversibility can be obtained within certain
      limits in the two organs. Evidence is presented which shows that in the 'fully
      green' plant there is an interorgan reaction whose primary reaction is the
      photoconversion of phytochrome. 

PMID- 24317856
TI  - The effect of caffeine, different fixation regimes and low temperature on
      microtubules in the cells of higher plants : Evidence for diversity in their
      response to chemical and physical treatments.
AB  - Caffeine, (1:3:7-tri-methyl-xanthine), either as a prefixation treatment or
      included with glutaralde-hyde as the primary fixative, destroys or disorganises
      the microtubules associated with the formation of secondary walls in fibres from
      the flowering stem of the grass Lolium temulentum L. There is no observable
      effect of caffeine treatment on the microtubules associated with primary wall
      formation in collenchyma and young fibres from L. temulentum or in root cap cells
      of Zea mays L. and Phaseolus vulgaris L. The microtubules associated with primary
      wall formation are destroyed by cold treatment but not those associated with
      secondary wall formation. Tannic acid included in the fixative shows the
      microtubules associated with secondary wall formation in fibres of L. temulentum
      to be composed of 13 subunits. Treatment with lanthanum hydroxide does not stain
      the core or the halo of the microtubules. 

PMID- 24317857
TI  - Membrane glycoproteins of Chlamydomonas eugametos flagella.
AB  - The flagellar glycoproteins exposed on Chlamydomonas eugametos gametes were
      labeled by means of lactoperoxidase, diiodosulfanilic acid and chloramine T, and
      characterised in SDS-electrophoresis gels. The medium from gamete cultures
      contains particles (isoagglutinins) that agglutinate gametes of the opposite
      mating type. When crude preparations of these particles were subjected to
      isopycnic centrifugation in a caesium chloride gradient, two bands of particles
      were found. The lighter, active band consisted of membrane vesicles. The denser,
      inactive band consisted of cell wall material. The active band had the same
      glycoprotein composition as membrane vesicles artificially made from isolated
      flagella. Preparations of glagella were also separated on a caesium chloride
      cushion into pure flagella and cell wall material. The flagella, but not the cell
      wall material, isoagglutinated opposite gametes. Again the glycoprotein
      composition of pure flagella was similar to that of pure isoagglutinin vesicles.
      No difference was detected between the protein and glycoprotein compositions of
      flagella and isoagglutinins from both mating types. 

PMID- 24317858
TI  - The role of electrical fields, ions, and the cortex in the morphogenesis of
      Acetabularia.
AB  - Electrophysiological and biochemical aspects of polarity determination and
      morphogenesis were studied in regenerating Acetabularia. The Ca(++), Mg(++)
      ionophore, A23187, reversibly inhibits the formation of apical structures (whorls
      and caps) but does not arrest longitudinal growth. This normal growth correlates
      with normal electrophysiology as reflected in an apico-basal electrical potential
      gradient and spontaneous recurrent action potentials which propagate from apex to
      base. However, the ionophore markedly elevates (32)PO 3 (3-) incorporation into
      the cortical cytoplasm which is normally low apically and rises to a maximum at
      the base. A molecular model of membrane-dependent morphogenesis is suggested. 

PMID- 24317859
TI  - Protein synthesis and auxin-induced growth: Inhibitor studies.
AB  - We have compared the effects of cycloheximide (CHI) and two other rapid and
      effective inhibitors of protein synthesis, pactamycin and 2-(4-methyl-2,6
      dinitroanilino)-N-methyl proprionamide (MDMP), on protein synthesis, respiration,
      auxin-induced growth and H(+)-excreation of Avena sativa L. coleoptiles. All
      three compounds inhibit protein synthesis without affecting respiration. The
      effectiveness of the inhibitors against H(+)-excretion and growth correlates with
      their ability to inhibit protein synthesis. Both CHI and MDMP inhibit auxin
      induced H(+)-excretion after a latent period of 5-8 min, and inhibit growth after
      a 8-10-min lag. These results support the idea that continued protein synthesis
      is required in the initial stages of the growth-promoting action of auxin. 

PMID- 24317860
TI  - The fine structure and development of the trabeculae and the trabecular ring in
      Selaginella kraussiana.
AB  - In the shoot apex of Selaginella kraussiana A. Br., air spaces develop between
      the endodermal cells, isolating the two steles from the cortex. The endodermal
      cells elongate to form trabeculae connecting the two tissues. As each trabecular
      cell develops, cuticularization occurs on the external surface at a point mid-way
      along the cell and forms the trabecular ring. The plasmalemma of the trabecular
      cell becomes attached to the wall beneath the main concentration of the ring,
      resembling the connection between the plasmalemma and the Casparian strip of a
      primary endodermis. The trabeculae retain a functional cytoplasm throughout
      growth. 

PMID- 24317861
TI  - Post-meiotic nucleo-cytoplasmic interaction in Cosmos bipinnatus : Early events
      at the nuclear envelope.
AB  - An interaction involving the nuclear envelope and spherical double-membrane bound
      inclusions takes place in the cytoplasm of post-meiotic male microspores of
      Cosmos (tribe Heliantheae, sub-tribe Coreopsidinae). The identity of the
      spherical inclusions has yet to be fully established, but they closely resemble
      profiles elsewhere in the cytoplasm, themselves presumably derived from the
      mitochondrial population of the premeiotic pollen mother cells. Both the
      cytoplasmic and nucleaar-associated inclusions regularly contain a central
      'vesicle', formed by an ingagination of their bounding membranes. The
      interaction, which occurs immediately prior to the deposition of the primexine of
      the pollen wall, involves the adhesion of the inclusions to the nuclear surface.
      Experiments with osmotically disrupted cells reveal that the inclusions are
      firmly bound to the envelope and, at the points of contact, electron opaque
      granules are regularly present. Frequently elements of the chromatin may be
      observed in juxtapostion to these points of contact, but on the inner face of the
      envelope. The interaction in Cosmos is proposed to constitute part of the process
      by which the cytoplasm and its content are realigned to the new "gametophylic"
      style of growth. 

PMID- 24317862
TI  - Heterogeneity in phloem protein complements from different species : Consequences
      of hypotheses concerned with P-protein function.
AB  - Protein subunits present in phloem exudate from 17 cultivars, 5 species and 3
      genera of the Cucurbitaceae have been fractionated by SDS-gel electrophoresis.
      The degree of difference in the phloem protein patterns appears to reflect the
      taxonomic relationships of the plants: there were major differences among genera,
      significant differences and similarities among species, and relatively few
      differences among cultivars of a single species. A representative of another
      family (Acer pseudoplatanus; Aceraceae) provided a completely different
      electrophoretic pattern. Each plant displayed a consistent protein pattern,
      irrespective of the organ from which exudate was obtained or the age and
      physiological status of the plant. Neither complete etiolation nor transition to
      the flowering phase effected any change in phloem proteins. The differences in
      phloem proteins between plants and the unusual properties of major subunits from
      different protein complements, render improbable many of the present ideas
      concerning the origin and function of P-protein. 

PMID- 24317863
TI  - Effects of silver on ethylene synthesis and action in cut carnations.
AB  - Silver, applied as silverthiosulphate, completely blocked the ethylene surge
      preceding the wilting of the petals. As a consequence, vase life was extended by
      nearly 100%. In addition, a pretreatment with silverthiosulphate caused the
      flowers to become insensitive to an ethylene treatment. 

PMID- 24317864
TI  - Morphology and ultrastructure of the gravity-sensitive leaf sheath base of the
      grass Echinochloa colonum L.
AB  - When a flowering stalk of Echinochloa colonum is held horizontally, growth is
      initiated in the lower side of each leaf sheath base, restoring the inflorescence
      to an upright position. Changes in the gravity vector are perceived by
      specialised statolithcontaining tissue which is associated with each of the
      symmetrically-arranged vascular bundles within the leaf sheath bases. The
      morphological and ultrastructural features of these gravity-sensitive regions
      have been examined by light and electron microscopy. Each statocyte cell contains
      a large central vacuole with a thin lining of cytoplasm. Up to 50 spherical
      starch statoliths lie along the lowermost side of the cells and these sediment
      readily following geotropic stimulation. Statoliths are found in contact with the
      plasmalemma, or may be prevented from touching it by bands of microtubules.
      Dictyosomes and mitochondria are numerous, but endoplasmic reticulum is sparse.
      The nuclei tend to remain at the original apex of each cell. Statocytes of the
      leaf sheath base are compared and contrasted with those of the root tip. 

PMID- 24317865
TI  - Positional specificity in the incorporation of isomeric cis- and trans
      octadecenoic acids into glycerolipids of cultured soya cells.
AB  - Heterotrophically grown cell suspension cultures of soya (Glycine max L.) were
      incubated with two different mixed substrates consisting of positional isomers of
      either cis-[1-(14)C]octadecenoic acids (Delta8 to delta15) or trans-[1
      (14)C]octadecenoic acids (Delta8 to Delta16), each with known composition. With
      both substrates, about one-fourth of the radioactivity supplied was incorporated
      into the diacylglycerophosphocholines, while another one-fourth of the
      radioactivity was almost equally distributed between diacylglycerophos
      phoethanolamines and triacylglycerols. All the positional isomers of cis-and
      trans-octadecenoic acids supplied to the cells were readily incorporated into
      various classes of glycerolipids. None of the octadecenoic acids was isomerized,
      elongated or desaturated during incubation. From the cis-octadecenoic acids, only
      the naturally occurring Delta9-isomer (oleic acid) was preferentially
      incorporated into position 2 of diacylglycerophosphocholines,
      diacylglycerophospho-ethanolamines, and triacyglycerols; all the other isomers
      exhibited a strong affinity for position 1 of the glycerophospholipids and
      positions 1 and 3 of the triacylglycerols. From the trans-octadecenoic acids,
      only the Delta9-isomer (elaidic acid) was preferentially incorporated into
      position 2 of diacylglycerophospho-cholines and triacylglycerols; all the other
      isomers preferred position 1 and positions 1 and 3, respectively, of these
      lipids. In diacylglycerophospho-ethanolamines, however, each of the trans
      octadecenoic acids, including the Delta9-isomer, exhibited a strong affinity for
      position 1. Apparently, the enzymes involved in the incorporation of exogenous
      monounsaturated fatty acids into membrane lipids of plant cells can recognize the
      preferred substrate in a mixture of closely related isomers. 

PMID- 24317866
TI  - Isolation and metabolism of Vigna unguiculata root nodule protoplasts.
AB  - Axenic cultures of bacteroid-containing protoplasts were isolated from root
      nodules of Vigna unguiculata L. Walp. Dimensions of the protoplasts were 35 to
      135 MUm long x 35 to 95 MUm wide. Yields were about 30 to 50 mg dry weight per
      gram fresh weight of nodules. About 5x10(8) protoplasts packed into 1 ml of basal
      medium under the influence of gravity. When incubated in hypertonic, nitrogen
      free media, freshly isolated protoplasts began to reduce acetylene to ethylene
      after a lag period of 24 to 48 h. Various additions to the basal medium showed
      that the system possessed functional glycolytic and tricarboxylic acid pathways.
      Endogenous application of various intermediary metabolites stimulated both
      acetylene reduction and respiration, though not often equally. As acetylene
      reduction, but not respiration, was inhibitable by both asparagine and glutamine,
      the system appears suitable for the study of mechanisms controlling symbiotic
      nitrogen fixation. 

PMID- 24317867
TI  - Inhibition of carotenoid biosynthesis by the herbicide SAN 9789 and its
      consequences for the action of phytochrome on plastogenesis.
AB  - Treatment of the mustard (Sinapis alba L.) seedling with the herbicide SAN 9789
      inhibits synthesis of colored carotenoids and interferes with the formation of
      plastid membrane lipids without affecting growth and morphogenesis significantly.
      In farred light, which is hardly absorbed by chlorophyll, development of plastid
      ultrastructure, synthesis of ribulosebisphosphate carboxylase and synthesis of
      chlorophyll are not affected by SAN 9789. It is concluded that normal phytochrome
      actions on plastid structural development, protein and chlorophyll syntheses are
      not affected by the absence of carotenoids provided that there is no significant
      light absorption in chlorophyll. The findings show that the inhibition of
      synthesis of one set of plastid membrane components (the carotenoids) does not
      stop synthesis of other components such as chlorophyll and does not halt membrane
      assembly. Supplementary experiments with the closely related compound SAN 9785,
      which affects the amount and composition of plastid lipids but not carotenoid and
      chlorophyll syntheses, suggest that the effect of the herbicide SAN 9789 is due
      exclusively to its inhibition of synthesis of colored carotenoids. In the
      presence of SAN 9789 white or red light at high fluence rate causes
      photodestruction of chlorophyll and ribulosebisphosphate carboxylase and
      photodecomposition of thylakoids. These effects are interpreted as resulting
      exclusively from the self-photooxidation and photosensitizing action of
      chlorophyll once the protection by carotenoids of chlorophyll against self- and
      sensitized photooxidation is lost. 

PMID- 24317868
TI  - Overcoming dormancy in seeds with ethanol and other anesthetics.
AB  - Dormancy in fall panicum (Panicum dichotomiflorum Michx.) caryopses (seeds) is
      overcome by imbibition at 35 degrees  C in ethanol solutions. Whereas germination
      in the absence of ethanol depends on active phytochrome, the seeds may germinate
      in darkness after treatment with 0.2 to 0.5 M ethanol. Ethanol overcomes dormancy
      also in seeds of several other weedy grass species. Ethyl ether, chloroform,
      methanol, and acetone act similarly to ethanol. We suggest that this action
      depends on modifyng the properties of a membrane(s) in a manner related to the
      actions of other anesthetics. 

PMID- 24317869
TI  - The influence of plant growth regulators on the growth of the embryonic axes of
      red- and far-red-treated lettuce seeds.
AB  - The influence of several plant growth regulators on the growth of the embryonic
      axes from red- and far-red-(R- and FR-)treated lettuce (Lactuca sativa L., cv.
      Grand Rapids) seeds was examined; as shown previously, the water potential of the
      axes from R-treated seeds has been lowered by 3.5-5.6 bars compared to that in
      axes from FR-treated ones. Kinetin and abscisic acid (ABA), when included in the
      incubation medium, reduced the elongation of the axes whereas fusicoccin
      stimulated it; however, these effects were the same in axes of both R- and FR
      treated seeds. In contrast, elongation of axes from FR-treated seeds was
      stimulated by gibberellic acid (GA3, but elongation of axes from R-treated ones
      was not affected by this hormone. This latter result indicates that gibberellins
      may be involved in the phytochrome-mediated growth responses in lettuce axes.When
      the root caps of the embryos were removed prior to light treatment, R was still
      able to induce a water-potential decrease in the embryonic axes, indicating that
      at least a portion of the active Pfr resides in the axis and not the root cap. 

PMID- 24317870
TI  - Evaluation of bootstrap methods for estimating uncertainty of parameters in
      nonlinear mixed-effects models: a simulation study in population
      pharmacokinetics.
AB  - Bootstrap methods are used in many disciplines to estimate the uncertainty of
      parameters, including multi-level or linear mixed-effects models. Residual-based
      bootstrap methods which resample both random effects and residuals are an
      alternative approach to case bootstrap, which resamples the individuals. Most
      PKPD applications use the case bootstrap, for which software is available. In
      this study, we evaluated the performance of three bootstrap methods (case
      bootstrap, nonparametric residual bootstrap and parametric bootstrap) by a
      simulation study and compared them to that of an asymptotic method (Asym) in
      estimating uncertainty of parameters in nonlinear mixed-effects models (NLMEM)
      with heteroscedastic error. This simulation was conducted using as an example of
      the PK model for aflibercept, an anti-angiogenic drug. As expected, we found that
      the bootstrap methods provided better estimates of uncertainty for parameters in
      NLMEM with high nonlinearity and having balanced designs compared to the Asym, as
      implemented in MONOLIX. Overall, the parametric bootstrap performed better than
      the case bootstrap as the true model and variance distribution were used.
      However, the case bootstrap is faster and simpler as it makes no assumptions on
      the model and preserves both between subject and residual variability in one
      resampling step. The performance of the nonparametric residual bootstrap was
      found to be limited when applying to NLMEM due to its failure to reflate the
      variance before resampling in unbalanced designs where the Asym and the
      parametric bootstrap performed well and better than case bootstrap even with
      stratification. 

PMID- 24317871
TI  - Heart rate variability (HRV) and muscular system activity (EMG) in cases of crash
      threat during simulated driving of a passenger car.
AB  - OBJECTIVES: The aim of the study was to verify whether simultaneous responses
      from the muscular and circulatory system occur in the driver's body under
      simulated conditions of a crash threat. MATERIALS AND METHODS: The study was
      carried out in a passenger car driving simulator. The crash was included in the
      driving test scenario developed in an urban setting. In the group of 22 young
      male subjects, two physiological signals - ECG and EMG were continuously
      recorded. The length of the RR interval in the ECG signal was assessed. A HRV
      analysis was performed in the time and frequency domains for 1-minute record
      segments at rest (seated position), during undisturbed driving as well as during
      and several minutes after the crash. For the left and right side muscles: m.
      trapezius (TR) and m. flexor digitorum superficialis (FDS), the EMG signal
      amplitude was determined. The percentage of maximal voluntary contraction (MVC)
      was compared during driving and during the crash. RESULTS: As for the ECG signal,
      it was found that in most of the drivers changes occurred in the parameter values
      reflecting HRV in the time domain. Significant changes were noted in the mean
      length of RR intervals (mRR). As for the EMG signal, the changes in the amplitude
      concerned the signal recorded from the FDS muscle. The changes in ECG and EMG
      were simultaneous in half of the cases. CONCLUSION: Such parameters as mRR (ECG
      signal) and FDS-L amplitude (EMG signal) were the responses to accident risk.
      Under simulated conditions, responses from the circulatory and musculoskeletal
      systems are not always simultaneous. The results indicate that a more complete
      driver's response to a crash in road traffic is obtained based on parallel
      recording of two physiological signals (ECG and EMG).

PMID- 24317872
TI  - Sensory preferences among general Japanese consumers and physicochemical
      evaluation of deep-fried peanuts.
AB  - BACKGROUND: The development of food that satisfies consumer preferences is very
      important for producing commodities. In the present study, 132 Japanese consumers
      carried out sensory evaluation of deep-fried peanuts with varying frying times
      (2, 4, 6, 9, 12 and 15 min) at 150  degrees C, and the relationships among
      sensory elements and physicochemical properties were investigated. RESULT: The
      sensory scores for colour, bitterness, and deep-fried peanut aroma increased
      (darker or stronger) with frying time, whereas the sweetness score was relatively
      high (strong) for frying times of 2, 4, 6 and 9 min, and then decreased (weaker)
      with increasing frying time. Frying times of 4, 6 and 9 min scored higher in
      overall liking than other times. Multiple-regression analysis indicated that the
      overall liking score was positively correlated with sweetness (standardised
      regression coefficient, beta = +0.51) and deep-fried peanut aroma (beta = +0.26)
      scores but negatively correlated with bitterness score (beta = -0.25). Multiple
      regression analysis also indicated a difference in sensory preference by gender.
      Sensory elements were closely related to the physicochemical properties,
      including the colour indexes (CIELAB colour space) and the sucrose and water
      contents. When L(*) (CIELAB colour space, lightness index) was 53-64 and water
      content was 10-30 g kg(-1), the mean overall liking score was relatively high
      implying acceptable fried peanut quality. CONCLUSION: Relationships among
      individual sensory elements were confirmed. Multiple-regression analysis
      indicated a strong positive correlation between sweetness and overall liking and
      a small difference in sensory preference by gender. Sensory evaluations can thus
      be expressed by physicochemical properties.

PMID- 24317873
TI  - Hybrid procedure and collaborative approach for hypoplastic left heart syndrome.

PMID- 24317874
TI  - TEVAR for type B aortic dissection in Japan.
AB  - TEVAR is a new strategy for treating both acute and chronic type B aortic
      dissection. The JSC guidelines classify TEVAR as a Class I recommendation for
      cases of complicated acute type B dissection and a Class IIa recommendation for
      cases of chronic type B aortic dissection. While TEVAR has been primarily applied
      to treat complicated acute type B aortic dissection in Europe and the USA, the
      procedure remains an off-label treatment strategy for aortic dissection in Japan.
      The current state of TEVAR for type B aortic dissection in Japan from 2001 to
      2011 is estimated in the annual reports of the Japanese Association for Thoracic
      Surgery. The number of acute type B aortic dissection patients treated with
      transluminal stent grafting increased rapidly after 2008, from 10 cases in 2001
      to 76 cases in 2010. Meanwhile, the number acute type B aortic dissection
      patients treated with any type of surgery has increased gradually, from 100 cases
      in 2001 to 194 cases in 2009. The number of chronic type B aortic dissection
      patients treated with transluminal stent grafting increased abruptly in 2010,
      reaching 346 cases, which accounted for one-third of all surgical procedures for
      chronic type B aortic dissection. Furthermore, the number of open surgeries for
      chronic type B aortic dissection has also increased gradually, from 401 cases in
      2001 to 947 cases in 2011. At present, open surgery, TEVAR and hybrid procedures
      are available to treat patients with type B aortic dissection. The use of a
      multidisciplinary team approach is mandatory when selecting the appropriate
      surgical strategy.

PMID- 24317875
TI  - Memorial address for Togo Horiuchi (1924-2012).

PMID- 24317876
TI  - Characterization of maxillary central incisor: novel crown-root relationships.
AB  - OBJECTIVES: The periodontal biotype includes crown features of the maxillary
      central incisor (MCI), whereas root measures have been less studied. The aim of
      our study was to morphologically characterize MCI and search relationships
      between crown and root measures. MATERIAL AND METHODS: One hundred-fifty MCIs
      were used. On each tooth, several crown and root reference points were marked and
      the following measures were done: On crown: mesio-distal (MD = major, md =
      minor), axial (crown length, cervical convexity) and buccolingual diameters
      (Cbl); On root: mesio-distal (Rmd) and buccolingual diameters (Rbl); and tooth
      length. A ratio between md and MD was made in order to assess dental forms. Root
      diameter prediction was assessed by means of multiple and single linear
      regression analyses, with variable selection by backward method. Reliability of
      measurements was estimated by the Pearson correlation coefficient. RESULTS:
      Dental form groups were: Stout type 56.67 %, Intermediate type 22.67 %, and
      Strangled type 20.67 %. A significative association was found between Rbl and Cbl
      (p = 0,000), Rmd with md (p = 0.000), and Rmd with MD (p = 0.000). The results
      allow predicting root diameters through crown measures. CONCLUSIONS: There is a
      direct relationship between crown and root features, which allows the prediction
      of root diameters with a high accuracy (95 %), regardless of tooth form. CLINICAL
      RELEVANCE: The morphometric data assess tooth diameters more accurately and could
      improve treatment planning, offering a more comprehensive approach to the
      periodontal biotype concept.

PMID- 24317877
TI  - Apoptosis: an underlying factor for accelerated periodontal disease associated
      with diabetes in rats.
AB  - OBJECTIVES: Diabetes mellitus (DM) is well-established risk factor for
      periodontal disease. DM can also lead to changes in the number of apoptotic cells
      in periodontal tissues. The goal of this study was to evaluate apoptosis,
      depending on DM, in healthy and diseased periodontal soft tissues. MATERIAL AND
      METHODS: A total of 43 adult male Sprague-Dawley rats were used in this study.
      Experimental periodontitis was created by placing silk ligatures around the
      cervices of the first mandibular molars. Experimental diabetes was induced by
      intraperitoneal injection of the diabetogenic agent streptozotocin (STZ).
      Following the induction of both experimental diseases, the animals were divided
      into four groups: (1) The healthy group (H) (n = 10); (2) The diabetes group (D)
      (n = 10); (3) The periodontitis group (P) (n = 11); and (4) The diabetes and
      periodontitis group (DP) (n = 12). Apoptotic cells were determined by
      immunohistochemistry, and the frequency of apoptotic cells was evaluated by
      apoptotic index score. RESULTS: It was observed that there was less apoptosis in
      both the epithelial and gingival connective tissue cells of healthy diabetic
      tissues than in healthy tissues without diabetes. When periodontal disease
      existed, apoptosis increased in both the epithelial and gingival connective
      tissues of diabetic and non-diabetic animals. CONCLUSIONS: There may be
      differences in the apoptotic mechanisms in the periodontal soft tissues of
      diabetic and non-diabetic animals. CLINICAL RELEVANCE: Apoptosis may be one of
      the underlying factors in increased risk for periodontal disease that is
      associated with diabetes.

PMID- 24317878
TI  - Changing the awareness of low vitamin D status in a rheumatology population: a
      pre/post-study.
AB  - INTRODUCTION: In 2009 hypovitaminosis D was highly prevalent in a population of
      Swiss rheumatology patients (86%). We aimed to evaluate the evolution of vitamin
      D status in the same population two years later, after the results of the first
      study were disseminated to local physicians and patients, in order to determine
      the evolution of the problem and the impact of physician information. METHOD:
      Patients in our rheumatology clinic were screened for 25-OH vitamin D. Results
      were categorised as: deficient (<10 ng/ml or <25 nmol/l), insufficient (10 to 30
      ng/ml or 25 to 75 nmol/l) or normal (>30 ng/ml or >75 nmol/l). We also used
      another cut-off of 20 ng/ml (50 nmol/l). We evaluated the evolution of 25-OH
      vitamin D dosages and vitamin D3 prescriptions between 2008 and 2011 in our
      institution and the number of publications on vitamin D in three important
      medical journals of the French speaking part of Switzerland. RESULTS: Compared
      with 2009, significantly more patients had normal results in 2011. Fifty-two
      percent of patients had levels >20 ng/ml in 2009 and 66% in 2011, difference
      statistically significant (p = 0.001). During the years separating the two study
      periods the number of 25-OH vitamin D dosages and the prescription of high doses
      of vitamin D3 increased in our hospital. In addition the number of publications
      on vitamin D increased between 2008 and 2011. CONCLUSION: We concluded that lower
      prevalence in hypovitaminosis D is certainly related to better adherence to daily
      supplements, and to better information and awareness of the physicians about
      hypovitaminosis D.

PMID- 24317879
TI  - Metabolic patterns of the shoulder joint on (18)F-fluorodeoxyglucose positron
      emission tomography/computed tomography in adhesive capsulitis.
AB  - OBJECTIVE: The purpose of our study was to demonstrate metabolic patterns on
      (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F
      FDG PET/CT) in patients with adhesive capsulitis (AC). METHODS: We
      retrospectively reviewed (18)F-FDG PET/CT performed on 22 shoulders of 21
      patients diagnosed with AC: 2 shoulders with stage I, 14 with stage II, and 6
      with stage III. A clinical diagnosis of AC was retrospectively made based on
      clinical examination, clinical course, and imaging. The pattern of radiotracer
      uptake was analyzed. Standardized uptake values in rotator interval (RI),
      anterior joint capsule (AJC), axillary recess (AR), and greater tuberosity were
      measured and compared to those of the contralateral side and the control group
      consisting of 40 shoulders in 20 subjects without shoulder pain. RESULTS: Four
      patterns of uptake were noted: (1) glenoid type I (n = 16), with uptake in RI,
      AJC, and AR; (2) glenoid type II (n = 2),with uptake in AJC and AR; (3) glenoid
      type III (n = 2), with uptake in RI and AJC; (4) focal type (n = 2), with uptake
      in RI or AR. Affected side SUVmax for RI, AJC, and AR was significantly higher
      compared with the unaffected side and the control group. Two shoulders with stage
      I AC had patterns similar to the ones with stage II or III. CONCLUSION: Specific
      patterns of (18)F-FDG uptake with dominant uptake in RI, AJC, or AR may be
      related to AC.

PMID- 24317881
TI  - [Image-guided surgery for motor eloquent area glioma supported by intraoperative
      MRI].

PMID- 24317880
TI  - Analysis of in vitro fertilization data with multiple outcomes using discrete
      time-to-event analysis.
AB  - In vitro fertilization (IVF) is an increasingly common method of assisted
      reproductive technology. Because of the careful observation and follow-up
      required as part of the procedure, IVF studies provide an ideal opportunity to
      identify and assess clinical and demographic factors along with environmental
      exposures that may impact successful reproduction. A major challenge in analyzing
      data from IVF studies is handling the complexity and multiplicity of outcome,
      resulting from both multiple opportunities for pregnancy loss within a single IVF
      cycle in addition to multiple IVF cycles. To date, most evaluations of IVF
      studies do not make use of full data because of its complex structure. In this
      paper, we develop statistical methodology for analysis of IVF data with multiple
      cycles and possibly multiple failure types observed for each individual. We
      develop a general analysis framework based on a generalized linear modeling
      formulation that allows implementation of various types of models including
      shared frailty models, failure-specific frailty models, and transitional models,
      using standard software. We apply our methodology to data from an IVF study
      conducted at the Brigham and Women's Hospital, Massachusetts. We also summarize
      the performance of our proposed methods on the basis of a simulation study.

PMID- 24317882
TI  - [Gamma knife radiosurgery for trigeminal neuralgia: analysis of a multi
      institutional study].
AB  - A multi-institutional study was conducted to evaluate the results of gamma knife
      radiosurgery (GKRS) for the treatment of trigeminal neuralgia. Eleven hundred and
      thirty-five patients at 39 centers were analyzed. Three hundred and sixty-nine
      patients had undergone percutaneous nerve block and 173 patients had undergone
      microvascular decompression (MVD) prior to GKRS. GKRS was performed for 69.4% of
      patients targeted at the nerve root entry zone (REZ) and for 20.4% of patients
      targeted at the retrogasserian region (RGR). The target dose of the GKRS used in
      the current study varied from 70 to 90 Gy (mean: 77.8Gy). The median follow-up
      period after GKRS was 21.1 months (range 1 to 125 months). Six hundred and eighty
      nine patients (66%) responded with excellent or good control (pain free), 157
      (15%) obtained fair control (more than 50% relief), and 192 (19%) experienced
      treatment failure. After 3 years, 64% of cases were pain free and 80% had more
      than 50% pain relief. After 4 years, 37 patients underwent additional GKRS, 36
      MVD and 36 percutaneous nerve block. Tolerable hypoesthesia or paresthesia
      occurred in 129 patients (11%), whereas bothersome symptoms developed in 8
      patients (1%). But no patient developed deafferentation pain. Nine patients (1%)
      complained of dry eye, but no other abnormalities of the cornea and conjunctiva
      were found on ophthalmological examination. Higher maximum radiosurgical dose was
      associated with a significantly greater factor of complete pain relief
      (p=0.0101). GKRS is a safe and effective alternative treatment for trigeminal
      neuralgia, and is a minimally invasive treatment. In addition it provided benefit
      to a patient population unwilling or unable to undergo more invasive surgical
      approaches.

PMID- 24317883
TI  - [Efficacy of fusion image for the preoperative assessment of anatomical variation
      of the anterior choroidal artery].
AB  - We report two cases with internal carotid artery(ICA)aneurysms, in which fusion
      image effectively indicated the anatomical variations of the anterior choroidal
      artery (AchoA). Fusion image was obtained using fusion application software
      (Integrated Registration, Advantage Workstation VS4, GE Healthcare). When the
      artery passed through the choroidal fissure, it was diagnosed as AchoA. Case 1
      had an aneurysm at the left ICA. Left internal carotid angiography (ICAG) showed
      that an artery arising from the aneurysmal neck supplied the medial occipital
      lobe. Fusion image showed that this artery had a branch passing through the
      choroidal fissure, which was diagnosed as hyperplastic AchoA. Case 2 had an
      aneurysm at the supraclinoid segment of the right ICA. AchoA or posterior
      communicating artery (PcomA) were not detected by the right ICAG. Fusion image
      obtained from 3D vertebral angiography (VAG) and MRI showed that the right AchoA
      arose from the right PcomA. Fusion image obtained from the right ICAG and the
      left VAG suggested that the aneurysm was located on the ICA where the PcomA
      regressed. Fusion image is an effective tool for assessing anatomical variations
      of AchoA. The present method is simple and quick for obtaining a fusion image
      that can be used in a real-time clinical setting.

PMID- 24317884
TI  - [A patient with vertebral artery dissection who initially suffered from
      pharyngeal pain].
AB  - We have encountered a case of a patient with bilateral vertebral artery (VA)
      dissection who suffered from severe pharyngeal pain. A 61-year-old man, who
      initially visited a nearby hospital for investigation of mild headache, was
      pointed out to have a left VA aneurysm. The next morning, severe pharyngeal pain
      on the right side suddenly occurred. The cause was unknown even when consultation
      was made to an otolaryngology and oral and maxillofacial surgeon. Sore throat
      improved in two days. On the 12th day after pharyngeal pain, the patient entered
      our hospital with a diagnosis of VA dissection. Imaging studies indicated severe
      stenosis of the right VA and an aneurysm of the left VA which confirmed the
      diagnosis of bilateral VA dissection. After severe stenosis of the right VA
      improved a little, the trapping of the left VA aneurysm was performed with bypass
      surgery of the occipital artery to the posterior inferior cerebellar artery.
      Although there have been reports of glossopharyngeal neuralgia due to compression
      of dissective aneurysms of VA, no report exists in terms of a sore throat due to
      VA dissection without glossopharyngeal neuralgia. This symptom was considered to
      be involved in the referred pain.

PMID- 24317885
TI  - [A case of neurosurgery for meningioma in a chronic hemodialysis patient:
      perioperative management of chronic hemodialysis patients requiring
      neurosurgery].
AB  - Here, we report a case of primary intracranial tumor in a chronic hemodialysis
      patient in which neurosurgery was successful. A 50-year-old man who had been on
      hemodialysis for 4 years was admitted to our hospital with general fatigue.
      Neurological examination on admission revealed mild restless. Computed tomography
      and magnetic resonance imaging performed on admission revealed a large (55 mm*40
      mm) tumor mass in contact with the falx. The size of this tumor rapidly increased
      over the next month. 201Thallium-chloride single photon emission computed
      tomography revealed abnormal uptake in the same location as the lesion. This
      suggested a malignant brain tumor and surgical excision was scheduled. Two weeks
      prior to surgery, frequent hemodialysis was performed using nafamostat mesilate
      instead of heparin to prevent bleeding and to maintain electrolyte balance, and
      red cell concentrates and erythropoietin were administered for the improvement of
      anemia. A triple lumen catheter was inserted in the right internal jugular vein
      in preparation for emergency continuous hemodiafiltration to maintain homeostasis
      of circulatory dynamics. Surgery was completed without incident and the tumor was
      resected totally. During surgery, cerebral edema was well controlled by
      hyperventilation and a slightly upturned head position. Histopathological
      examination of the specimen confirmed atypical meningioma. Continuous
      hemodiafiltration was performed for 24 hours after surgery, and hemodialysis was
      initiated on the third day after surgery. The postoperative course was
      uneventful. Three weeks after surgery, the patient was discharged with no
      neurological deficit and resumed his daily life on maintenance hemodialysis.

PMID- 24317886
TI  - [Surgical seeding of an anaplastic ependymoma].
AB  - Ependymomas can relapse at the primary site and disseminate to the spinal cord.
      Furthermore, extraneural metastases are rare. We present a case of anaplastic
      ependymoma with extraneural metastasis, possibly caused by surgical seeding. An
      18-year-old female was referred to us after experiencing frequent convulsive
      attacks. At age 9 years, she underwent partial resection of a left frontal
      anaplastic ependymoma, followed by 45 Gy radiation. At age 15 years, a recurrent
      tumor was totally removed. Three years later, magnetic resonance images revealed
      a left frontal recurrent tumor and a new parietal lesion. Our preoperative
      diagnosis of the parietal tumor was a radiation-induced meningioma. However,
      intraoperative pathological examinations revealed the lesion to be an anaplastic
      ependymoma. The tumor, which was located in the epidural space and had invaded
      extensively into the cranial bone, was gross totally removed. Although extremely
      rare, surgical seeding of anaplastic ependymomas should be considered as a
      differential diagnosis for recurrent tumors in the surgical field. 

PMID- 24317888
TI  - [Endovascular treatment for traumatic carotid-cavernous fistula].

PMID- 24317887
TI  - [Ulcerative colitis in remission with cerebral abscess and septic pulmonary
      emboli: a case report].
AB  - A 69-year-old man with a 4-year history of ulcerative colitis (UC) presented at
      our hospital with high fever, dysarthria, and right hemiparesis. Computed
      tomography (CT) of the head revealed a low-density area in the left temporal
      lobe. Chest CT exposed multiple pulmonary nodules in his right lung. Gadolinium
      enhanced magnetic resonance imaging (MRI) indicated a 3-cm tumor with ring
      enhancement located in the left temporal lobe. The patient was diagnosed with a
      brain abscess and septic pulmonary emboli (SPE); antibiotic therapy was
      initiated. Shrinkage of the brain abscess was not observed in a follow-up
      MRI;thus, he underwent aspiration and drainage of the abscess 11 days after his
      hospitalization. Intravenous antibiotic therapy was continued for 6 weeks after
      the operation. Follow-up chest CT performed 48 days after his hospitalization
      revealed disappearance of the SPE. Follow-up head MRI conducted 63 days after his
      hospitalization indicated that the cyst had almost disappeared. Occurrence of a
      brain abscess in patients with UC has been very rarely reported in Japan. To the
      best of our knowledge, this is the first report of a case of a brain abscess in
      conjunction with UC and SPE. It is believed that patients with UC have
      compromised immunity and exhibit activation of the blood coagulation system. Our
      report suggests that medical practitioners should consider the possibility of a
      brain abscess and SPE for patients with UC.

PMID- 24317889
TI  - [Systematic review of complication for proper informed consent (11) STA-MCA
      bypass surgery].
AB  - Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is
      commonly used to prevent subsequent ischemic stroke in patients with hemodynamic
      compromise or to assist in the treatment of aneurysms. In this systematic review,
      we surveyed articles about surgical complications of STA-MCA anastomosis as
      comprehensively as possible. Since there are few serious complications with STA
      MCA anastomosis, this procedure seems to be safe. However, even comparatively
      rare complications may cause permanent neurological deficits.

PMID- 24317890
TI  - [Required knowledge for spinal surgeon (4) posterior approach for cervical spine:
      myoarchitectonic spinolaminoplasty].

PMID- 24317891
TI  - Mitochondrial gene expression and cytoplasmic male sterility in sorghum.
AB  - Variation in sorghum mitochondrial translation products has enabled fertile
      (Kafir) cytoplasm to be distinguished from Milo cytoplasmic male sterile
      cytoplasm and from three alternative sources of cytoplasmic male sterile
      cytoplasm. Mitochondria from Milo cytoplasm synthesised a 65 000 mol. wt.
      polypeptide which was not synthesised by those from Kafir cytoplasm. In the
      cytoplasmic male sterile combination of Kafir nucleus in Milo cytoplasm synthesis
      of this polypeptide was dramatically increased. Mitochondria from two cytoplasmic
      male sterile lines (Kafir nucleus in IS1112 cytoplasm and Yellow Feterita nucleus
      in M35-1 cytoplasm) did not synthesise the 65 000 mol. wt. polypeptide but
      synthesised additional high molecular weight polypeptides (from 54 000 to 82 000
      mol. wt.), the major one being 82 000. Mitochondria from cytoplasm IS1112 were
      also distinguished by synthesis of an additional 12 000 mol. wt. polypeptide.
      Mitochondria from the cytoplasmic male sterile line Martin nucleus in 9E
      cytoplasm synthesised an additional 42 000 mol. wt. polypeptide but did not
      synthesise a 38 000 mol. wt. polypeptide detected in all other cytoplasms.
      Immunoprecipitation of mitochondrial translation products with antiserum raised
      against subunit I of yeast cytochrome oxidase tentatively identified the 38 000
      mol. wt. polypeptide as subunit I of sorghum cytochrome oxidase. The 42 000 mol.
      wt. polypeptide was also immuno-precipitated by this antiserum and thus is
      probably an altered form of cytochrome oxidase subunit I.Analysis of native
      mitochondrial DNA by agarose gel electrophoresis revealed the presence of two
      'plasmid-like' DNA species of molecular weight 5.3 and 5.7 kb in the cytoplasmic
      male sterile lines Kafir nucleus in cytoplasm IS1112 and Yellow Feterita nucleus
      in M35-1 cytoplasm. Thus there is a positive correlation between the synthesis of
      the 82 000 mol. wt. polypeptide and the presence of the additional DNA species. 

PMID- 24317892
TI  - Heat shock proteins and effects of heat shock in plants.
AB  - Soybean seedlings when exposed to a heat shock respond in a manner very similar
      to that exhibited by cultured cells, and reported earlier [2]. Maximum synthesis
      of heat shock proteins (HSPs) occurs at 40C. The heat shock response is
      maintained for a relatively short time under continuous high temperature. After
      2.5 hr at 40 C the synthesis of HSPs decreases reaching a very low level by 6 hr.
      The HSPs synthesized by cultured cells and seedlings are identical and there is a
      large degree of similarity in HSPs synthesized between the taxonomically widely
      separated species, soybean and corn. Storage protein synthesis in the developing
      soybean embryo is not inhibited but is actually stimulated during a heat shock,
      unlike most other non-HSPs, whose synthesis is greatly reduced. Seedlings respond
      differently to a gradual increase in temperature than they do a sudden heat
      shock. There is an upward shift of several degrees in the temperature at which
      maximum protein synthesis occurs and before it begins to be inhibited. In
      addition, there appears to be a protection of normal protein synthesis from heat
      shock inhibition when the temperature increase is gradual. An additional function
      of the heat shock phenomenon might be the protection of seedlings from death
      caused by extreme heat stress. The heat shock response appears to have relevance
      to plants in the field. 

PMID- 24317893
TI  - Mapping of genes on the chloroplast DNA of Spirodela oligorhiza.
AB  - With the use of spinach chloroplast RNAs as probes, we have mapped the rRNA genes
      and a number of protein genes on the chloroplast DNA (cpDNA) of the duckweed
      Spirodela oligorhiz. For a more precise mapping of these genes we had to extend
      the previously determined [14] restriction endonuclease map of the duckweed cpDNA
      with the cleavage sites for the restriction endonucleases Sma I and Bgl I. The
      physical map indicates that duckweed cpDNA contains two inverted repeat regions
      (18 Md) separated by two single copy regions with a size of 19 Md and 67 Md,
      respectively.By hybridization with spinach chloroplast rRNAs it could be shown
      that each of the two repeat units contains one set of rRNA genes in the order:
      16S rRNA gene - spacer - 23S rRNA gene - 5S rRNA gene.A spinach chloroplast mRNA
      preparation (14S RNA), which is predominantly translated into a 32 Kilodalton
      (Kd) protein [9], hybridized strongly to a DNA fragment in the large single copy
      region, immediately outside one of the inverted repeats. With another mRNA
      preparation (18S), which mainly directs the in vitro synthesis of a 55 Kd protein
      [9], hybridization was observed with two DNA regions, located between 211 degrees
      and 233 degrees  and between 137 degrees  and 170 degrees , respectively.
      Finally, with a spinach chloroplast genomic probe for the large subunit of
      ribulose 1,5-bisphosphate carboxylase [17], hybridization was found with a DNA
      fragment located between 137 degrees  and 158 degrees  on the map. 

PMID- 24317894
TI  - The lysopinedehydrogenase gene used as a marker for the selection of octopine
      crown gall cells.
AB  - Plant cells transformed into octopine-synthesizing tumour cells by the bacterium
      Agrobacterium tumefaciens survive when cultured in the presence of homo-arginine
      (HA), whereas both normal plant cells and nopaline producing plant tumour cells
      do not. Survival of octopine crown gall cells is due to the activity of the
      enzyme lysopinedehydrogenase (LpDH) in these cells, which converts toxic homo
      arginine into non-toxic homo-octopine. The selective toxicity of homo-arginine
      for normal cells can be applied for the enrichment of octopine Ti plasmid
      transformed plant cells vs normal plant cells in mixed cultures. 

PMID- 24317895
TI  - Repeat sequence interspersion in coding DNA of peas does not reflect that in
      total pea DNA.
AB  - The pattern of sequence organization in the regions of the pea genome near
      sequences coding for mRNA differs significantly from that in total DNA.
      Interspersion of repeated and single copy sequences is so extensive that 85% of
      1300 nucleotide-long fragments contain highly repetitive sequences (about 5000
      copies per haploid genome). However, data presented here demonstrate that
      sequences which code for mRNA are enriched in the small fraction of fragments
      which do not contain these highly repetitive sequences. Thus, in contrast to the
      great majority of other sequences in the genome, most mRNA coding sequences are
      not located within 1300 nucleotides of highly repetitive elements. Moreover, our
      data indicate that those repeats (if any) which are closely associated with mRNA
      coding sequences belong to low copy number families characterized by an unusually
      low degree of sequence divergence. 

PMID- 24317896
TI  - Open reading frame in the minus strand of two plus type RNA viruses.
AB  - : Inspection of the nucleotide sequences of the RNAs complementary to the coat
      protein mRNAs from two plant viruses with a tripartite genome: alfalfa mosaic
      virus and brome mosaic virus, showed the presence of open reading frames for 138
      and 118 amino acids, respectively. A third virus (cowpea chlorotic mottle virus)
      from the same family (1) does not show this phenomenon. This suggests that if a
      protein is coded for by the open reading frames it may be not essential for virus
      multiplication. Alternatively the open reading frames have no coding function but
      result from structural requirements of the RNAs. 

PMID- 24317899
TI  - Paternal regulation of seed development in wheat hybrids.
AB  - Diallel crosses among Triticum boeoticum (4 lines from different geographical
      areas), T.urartu, Aegilops squarrosa and Ae. speltoides exhibited reciprocal
      differences in hybrid seed morphology, endosperm development, and embryo
      viability. T. urartu and Ae. squarrosa as females with T. boeotiaum and Ae.
      speltoides lead to shrivelled inviable seed. T.boeoticum accessions as female
      with Ae.speltoides also lead to shrivelled seeds. The reciprocal crosses produced
      plump seeds which either resembled the maternal parent or showed size
      differences. By altering the endospermic genome ratios, hybrid seeds with 1
      (PF)/1 (PM) showed extreme shrivelling whereas those with 4 (PF)/1 (PM) were
      medium shrivelled to plump. Genetic experiments involving hybrids of T.
      boeoticum, T. urartu and T. monococcum showed that a factor is present in pollen
      or male gametes, which shows dosage effect and which, by interacting with the
      maternal genome, leads to endosperm abortion. 

PMID- 24317898
TI  - Eggshell bacterial load is related to antimicrobial properties of feathers lining
      barn swallow nests.
AB  - The use of feathers to line bird's nests has traditionally been interpreted as
      having a thermoregulatory function. Feather-degrading bacteria growing on
      feathers lining nests may have antimicrobial properties, which may provide an
      additional benefit to lining nests with feathers. We test the hypothesis that the
      production of antimicrobial substances by feather bacteria affects the
      microbiological environment of the nest, and therefore the bacterial density on
      eggshells and, indirectly, hatching success. These effects would be expected to
      differ between nests lined with pigmented and white feathers, because bacteria
      grow differently on feathers of different colors. We experimentally manipulated
      the composition of pigmented and unpigmented feathers in nests of the barn
      swallow (Hirundo rustica) and studied the antimicrobial properties against the
      keratin-degrading bacterium Bacillus licheniformis of bacteria isolated from
      feathers of each color. Analyzed feathers were collected at the end of the
      incubation period, and antimicrobial activity was defined as the proportion of
      bacteria from the feathers that produce antibacterial substances effective
      against B. licheniformis. Our experimental manipulation affected antimicrobial
      activity, which was higher in nests with only white feathers at the beginning of
      incubation. Moreover, white feathers showed higher antimicrobial activity than
      black ones. Interestingly, antimicrobial activity in feathers of one of the
      colors correlated negatively with bacterial density on feather of the opposite
      color. Finally, antimicrobial activity of white feathers was negatively related
      to eggshell bacterial load. These results suggest that antimicrobial properties
      of feathers in general and of white feathers in particular affect the bacterial
      environment in nests. This environment in turn affects the bacterial load on
      eggshells, which may affect hatching success. 

PMID- 24317900
TI  - Trisomics from triploid-diploid crosses in self-incompatible Lycopersicum
      peruvianum : II. Transmission of trisomics.
AB  - The transmission rate of trisomy was determined for two primary trisomic types,
      triplo-1 and triplo-3, of the self-incompatible species Lycopersicum peruvianum.
      Chromosome counts in somatic metaphases of root-tip squashes from 112 progeny
      plants showed that 8 individuals (7.2 %) were trisomic and 104 (92.8%) were
      diploid. The average frequency of transmission approximated 2.6% in triplo-1 and
      8.6% in triplo-3. Data are presented on the karyotype and the morphological
      features of the 8 trisomics detected in the progenies of triplo-1 and triplo-3
      and the various factors affecting the transmission rate of trisomy are
      discussed.The transmission rate of trisomy was also determined for the trisomic
      plant 269 which displayed a complete deletion of the satellited part of
      chromosome 2 and was characterized by ovate fruits. Out of 18 progeny plants
      analysed, 8 (44.4%) were trisomic and 10 (55.6%) were diploid. Cytological and
      morphological analyses of the 8 trisomic individuals revealed that only two of
      them (11.1 %) resembled the parental trisomic. A number of diploid and trisomic
      progenies exhibited a partial or a complete deletion of the satellited segment of
      chromosome 2. 

PMID- 24317901
TI  - A variable selection index for the compensation of correlated genetic change.
AB  - A selection index for two traits has been constructed which allows partial
      restriction for one of the traits. The index is used in a situation where
      correlated response to selection in one sex is compenstated for by selection for
      other traits in the opposite sex. A numerical example is given. 

PMID- 24317902
TI  - Linear differentation of cereal chromosomes : III. Rye, triticale and 'Aurora'
      variety.
AB  - The BSG test was used in an investigation of the linear differentiation in rye
      variety 'Zhitkinskaya', common wheat variety 'Aurora' and two secondary Triticale
      namely AD-196 and F-1239.Chromosomes of 'Aurora' variety and wheat chromosomes
      within Triticale may be easily divided into "constant" and 'variable' chromosomes
      as described previously (lordansky et al. 1977; Zurabishvili et al 1977).It is
      necessary to emphasize that the diversity of "variable" chromosomes underlies
      karyotypical polymorphism within wheat and Triticale species. The polymorphism
      observed exists in parallel with strict homomorphism of homologous chromosomes.In
      IB chromosomes of 'Aurora' variety, the short arm is substituted by the rye
      chromosome arm. The karyotype of Triticale AD-196 consists of six pairs of rye
      chromosomes and fifteen pairs of wheat chromosomes. 

PMID- 24317903
TI  - The value of indirect selection : II. Progeny testing.
AB  - Conditions are developed under which progeny-testing using indirect selection can
      give more rapid genetic improvement than using direct selection. Analogous
      conditions for mass selection are given in Searle [1954]. 

PMID- 24317904
TI  - Genetic basis of seed setting in alfalfa.
AB  - The genetic basis of seed setting was evaluated in seven clones of alfalfa
      selected under predominantly self-pollinating conditions. They were hand crossed
      in all possible combinations. Their compatibility was studied by the percentage
      of flowers forming pods and number of seeds per pod during crossing. The
      variances for GCA, SCA and reciprocal effects were significant for percentage of
      pod set with a narrow sense heritability of 64 %. This suggested maternal
      influence of clones on percent pod set, controlled primarily by additive genetic
      components. GCA was the only significant component for number of seeds per pod
      with a narrow sense heritability of 71%. There were wide differences between the
      clones in their relative magnitude of GCA, SCA and reciprocal effects for both
      traits used as compatibility indexes. Performance of the diallel crosses was
      judged by studying seed yield and its related characters, namely seeds per pod,
      dry matter per plant, frost resistance, plant vigor and plant height. Although
      GCA and SCA variances were significant for all characters, reciprocal differences
      in general were absent. The SCA values were very high as compared to GCA. Narrow
      sense heritability values were very low while broad sense heritability were much
      higher. This suggested that almost none of the variation was due to additive
      genetic components and all the variability is controlled by interactions of a
      digenic, trigenic and quadrigenic nature and heterzozygosity. Heterosis was
      evaluated by comparing the seed yield of single crosses with their mid-parent and
      high-parent, and very high values were observed. Thus selection of better genes
      may not be feasible and further improvement in selected clones may have to be
      brought about by utilization of various interactions and heterosis. An attempt
      was made to find combinations of characters that may be used for the selection of
      seed yield but none were found to be satisfactory. 

PMID- 24317905
TI  - Epistatic contributions to quantitative traits in Tribolium castaneum : II.
      Traits closely related to fitness.
AB  - Triple-testcross experiments were used to analyze epistatic contributions to %
      hatchability of eggs, age of pupation, number of eggs laid in 24-hour period, and
      survival from hatching to day 35. Seven diverse inbred lines and the F1 produced
      by crossing the two tester lines were examined for the presence of epistasis.
      There was evidence of epistasis for each of the 4 traits in at least one of the 8
      lines tested. Epistasis was a major source of variation in survival in all of the
      lines tested. 

PMID- 24317906
TI  - A vigorous mutant sugarcane (Saccharum sp.) clone Co 527.
AB  - A vigorous fast growing mutant which ends vegetative growth sixty days earlier
      than the parent variety Co 527 was isolated from gamma irradiated vegetative
      buds. The mutant initially segregated but stabilized in the vM4 generation. Its
      growth rate was almost fifty per cent higher than Co 527 beginning in the early
      stages of growth. It produced a significantly higher early shoot population which
      enabled it to yield a higher number of millable canes at maturity. Economic
      characters like sucrose content and juice purity remained unaffected. This mutant
      had a chromosomal basis in that the number was 2 to 3 lower than in the parent
      variety. 

PMID- 24317907
TI  - Low temperature phototransformations of protochlorophyll(ide) in etiolated
      leaves.
AB  - By methods of difference and derivative spectroscopy it was shown that in
      etiolated leaves at 77 K three photoreactions of P650 protochlorophyllide take
      place which differ in their rates and positions of spectral maxima of the
      intermediates formed in the process: P650->R668, P650->R688, and P650->R697. With
      an increase of temperature up to 233 K, in the dark, R688 and R697 are
      transformed into the known chlorophyllide forms C695/684 and C684/676, while R668
      disappears with formation of a shorter wavelength form of protochlorophyllide
      with an absorption maximum at 643-644 nm.Along with these reactions, at 77 K
      phototransformations of the long-wave protochlorophyllide forms with absorption
      maxima at 658-711 nm into the main short-wave forms of protochlorophyllide are
      observed. At 233 K in the dark this reaction is partially reversible. This
      process may be interpreted as a reversible photodisaggregation of the pigment in
      vivo.The mechanism of P650 reactions and their role in the process of chlorophyll
      photobiosynthesis are discussed. 

PMID- 24317908
TI  - Chilling and photosynthetic productivity of field grown maize (Zea mays); changes
      in the parameters of the light-response curve, canopy leaf CO2 assimilation rate
      and crop radiation-use efficiency.
AB  - The effect of growth temperatures on the photosynthetic performance of field
      grown maize (Zea mays cv. LG11) was examined for crops sown on 1 May and 28 June
      1991. During the period of growth, 2 May to 10 August, the early-sown crop
      experienced temperatures below 10  degrees C on 33 occasions compared with only
      one for the crop sown on 28 June. The prolonged period of low temperatures
      throughout May and beginning of June were associated with a marked depression in
      CO2 assimilation rates at all light levels in the early-sown treatment. Chill
      induced depression of the photosynthetic light-response curve reflected a
      sustained reduction in canopy leaf photosynthesis and crop radiation-use
      efficiency (RUE). During the early stages of growth, RUE was 65% lower in the
      early- than late-sown treatment, with no marked recovery observed in the former
      treatment until approximately three weeks after chilling conditions had ceased.
      Data show a close correlation between chill-induced depression of quantum yield
      (Phi) and RUE, with corresponding reductions in the light-saturated rates of CO2
      assimilation (Pmax). The convexity of the light-response curve recovered most
      rapidly from chilling temperatures, and at least three weeks before any
      improvement in RUE. It is concluded that photosynthetic productivity of immature
      maize stands is less sensitive to changes in the convexity of the light response,
      than to changes in either Phi or Pmax. 

PMID- 24317909
TI  - Inhibition by phosphate of light-state transitions in cyanobacterial cells.
AB  - Light-state transitions in cyanobacteria are a rapid physiological adaptation
      mechanism which changes the distribution of excitation energy absorbed by the
      light-harvesting complexes between Photosystem II and Photosystem I. State
      transitions in two cyanobacterial species are shown to be inhibited by buffers
      containing 0.2-0.4 M phosphate. Both the state 1 and the state 2 transition are
      inhibited, so that cells may be locked in the state to which they were adapted
      before the addition of phosphate. The inhibition of the state 1 transition is due
      to inhibition of photosynthetic electron transport. However, the inhibition of
      the state 2 transition is probably due to a direct effect on the biochemical
      signal transduction pathway. The implications for the biochemical mechanism of
      state transitions are discussed. 

PMID- 24317910
TI  - Assembly and composition of the chlorophyll a-b light-harvesting complex of
      barley (Hordeum vulgare L.): Immunochemical analysis of chlorophyll b-less and
      chlorophyll b-deficient mutants.
AB  - The chlorina-f2 mutant of barley (Hordeum vulgare L.) contains no chlorophyll b
      in its light-harvesting antenna, whereas the chlorina-103 mutant contains
      approximately 10% of the chlorophyll b found in wild-type. The absolute
      chlorophyll antenna size for Photosystem-II in wild-type, chlorina-103 and
      chlorina-f2 mutant was 250, 58 and 50 chlorophyll molecules, respectively. The
      absolute chlorophyll antenna size for Photosystem-I in wild-type, chlorina-103
      and chlorina-f2 mutant was 210, 137 and 150 chlorophyll molecules, respoectively.
      In spite of the smaller PS I antenna size in the chlorina mutants, immunochemical
      analysis showed the presence of polypeptide components of the LHC-I auxiliary
      antenna with molecular masses of 25, 19.5 and 19 kDa. The chlorophyll a-b-binding
      LHC-II auxiliary antenna of PS II contained five polypeptide subunits in wild
      type barley, termed a, b, c, d and e, with molecular masses of 30, 28, 27, 24 and
      21 kDa, respectively. The polypeptide composition of the LHC-II auxiliary antenna
      of PS II was found to be identical in the two mutants, with only the 24 kDa
      subunit d present at an equal copy number per PS II in each of the mutants and in
      the wild-type barley. This d subunit assembles stably in the thylakoid membrane
      even in the absence of chlorophyll b and exhibits flexibility in its complement
      of bound chlorophylls. We suggest that polypeptide subunit d binds most of the
      chlorophyll associated with the residual PS II antenna in the chlorina mutants
      and that is proximal to the PS II-core complex. 

PMID- 24317911
TI  - Fluorescence studies on interaction between phospho-LHC II and subchloroplast
      Photosystem 1 preparations.
AB  - Chloroplast proteins were phosphorylated under two test conditions: 'white light'
      irradiance alone and 'white light' irradiance with the addition of glucose and
      glucose oxidase, used to produce an anaerobic medium. The interaction of phospho
      LHC II with Photosystem 1 (PS 1) was studied for two types of PS I preparation.
      Changes in the chlorophyll a/b ratio and the ratio of 650 and 680 nm band
      intensities (E650/E680) in fluorescence excitation spectra were used in
      calculating the phospho-LHC II portion which became associated with PS 1. It is
      shown that the associated portion of phospho-LHC II varies for each of the PS 1
      preparations and phosphorylation procedures. Possible conclusions as regards the
      transfer of various sets of LHC II subpopulations under different phosphorylation
      procedures and the differences of interaction with PS 1 are discussed. 

PMID- 24317912
TI  - The effect of growth conditions on the light-harvesting apparatus in
      Rhodopseudomonas acidophila.
AB  - The detailed effect on the light-harvesting apparatus of three different wild
      type strains of Rhodopseudomonas acidophila in response to changes in both light
      intensity and temperature have been investigated. In all three strains at high
      light-intensities (160 MUmol s m(2) and above) the only LH2 antenna complex
      synthesised is the B800-850 complex. In strains 7050 and 7750 as the light
      intensity is lowered the B800-850 complex is gradually replaced by another type
      of LH2 the B800-820 complex. However, at no light-intensities studied is this
      changeover complete when the cells are grown at 30 degrees C. If however, the
      light-intensity is lowered at temperatures below 25 degrees C with strain 7750
      there is a complete replacement of the B800-850 complex by the B800-820 complex.
      At all light-intensities and temperatures tested, strain 10050 only synthesised
      the B800-850 complex. Strain 7050 also responded to changes in light-intensity by
      altering its carotenoid composition. At high light-intensity the major
      carotenoids were rhodopin and rhodopin-glucoside, while at low light-intensities
      the major ones were rhodopinal and rhodopinal-glucoside. This change in
      carotenoid content started to occur at rather higher light-intensities than the
      switchover from B800-850 to B800-820. 

PMID- 24317913
TI  - Flash-induced redox changes in oxygen-evolving spinach Photosystem II core
      particles.
AB  - Flash-induced redox reactions in spinach PS II core particles were investigated
      with absorbance difference spectroscopy in the UV-region and EPR spectroscopy. In
      the absence of artificial electron acceptors, electron transport was limited to a
      single turnover. Addition of the electron acceptors DCBQ and ferricyanide
      restored the characteristic period-four oscillation in the UV absorbance
      associated with the S-state cycle, but not the period-two oscillation indicative
      of the alternating appearance and disappearance of a semiquinone at the QB-site.
      In contrast to PS II membranes, all active centers were in state S1 after dark
      adaptation. The absorbance increase associated with the S-state transitions on
      the first two flashes, attributed to the Z(+)S1->ZS2 and Z(+)S2->ZS3 transitions,
      respectively, had half-times of 95 and 380 MUs, similar to those reported for PS
      II membrane fragments. The decrease due to the Z(+)S3->ZS0 transition on the
      third flash had a half-time of 4.5 ms, as in salt-washed PS II membrane
      fragments. On the fourth flash a small, unresolved, increase of less than 3 MUs
      was observed, which might be due to the Z(+)S0->ZS1 transition. The deactivation
      of the higher S-states was unusually fast and occurred within a few seconds and
      so was the oxidation of S0 to S1 in the dark, which had a half-time of 2-3 min.
      The same lifetime was found for tyrosine D(+), which appeared to be formed within
      milliseconds after the first flash in about 10% inactive centers and after the
      third and later flashes by active centers in Z(+)S3. 

PMID- 24317914
TI  - Photorespiration in C3-C 4 intermediate species of Alternanthera and Parthenium:
      Reduced ammonia production and increased capacity of CO2 refixation in the light.
AB  - The pattern of photorespiratory ammonia (PR-NH3) formation and its modulation by
      exogenous bicarbonate or glycine were investigated in C3-C4 intermediates of
      Alternanthera (A. ficoides and A. tenella) and Parthenium hysterophorus in
      comparison to those of C3 or C4 species. The average rates of PR-NH3 accumulation
      in leaves of the intermediates were slightly less than (about 25% reduced) those
      in C3 species, and were further low in C4 plants (40% of that in C3). The levels
      of PR-NH3 in leaf discs decreased markedly when exogenous bicarbonate was present
      in the incubation medium. The inhibitory effect of bicarbonate on PR-NH3
      accumulation was pronounced in C3 plants, very low in C4 species and was moderate
      in the C3-C4 intermediates. Glycine, an intermediate of photorespiratory
      metabolism, raised the levels of PR-NH3 in leaves of not only C4 but also C3-C4
      intermediates, bringing the rates close to those of C3 species. The rate of
      mitochondrial glycine decarboxylation in darkness in C3-C4 intermediates was
      partially reduced (about 80% of that in C3 species), corresponding to the
      activity-levels of glycine decarboxylase and serine hydroxymethyltransferase in
      leaves. The intermediates had a remarkable capacity of reassimilating
      photorespiratory CO2 in vivo, as indicated by the apparent refixation of about
      85% of the CO2 released from exogenous glycine in the light. We suggest that the
      reduced photorespiration in the C3-C4 intermediate species of Alternanthera and
      Parthenium is due to both a limitation in the extent of glycine
      production/decarboxylation and an efficient refixation/recycling of internal CO2.

PMID- 24317916
TI  - The prevalence and risk factors for atrioesophageal fistula after percutaneous
      radiofrequency catheter ablation for atrial fibrillation: the Canadian
      experience.
AB  - PURPOSE: Atrioesophageal fistula (AEF) is an infrequent complication of
      radiofrequency (RF) ablation for atrial fibrillation (AF). The aim of this study
      was to determine the prevalence and operator-dependent factors associated with
      AEF using a nationwide survey of electrophysiologists (EP). METHODS: Thirty-eight
      EPs performing AF ablation between 2008 and 2012 were invited to complete a web
      based questionnaire assessing the prevalence and factors associated with AEF.
      RESULTS: Responses were obtained from 25 EPs (68 %) accounting for 7,016 AF
      ablations. Five cases of proven AEF (0.07 %) were reported. Operators who
      reported AEF [AEF (+)] more often used general anesthesia (GA) [90 % AEF (+) vs.
      44 % AEF (-), p = 0.046]. AEF (+) operators were also more likely to be users of
      the non-brushing technique in the posterior wall of the LA [5 (100 %) AEF (+) vs.
      5 (25 %) AEF (-), p = 0.005]. The combined usage of GA and non-brushing technique
      during LA posterior wall ablation had a strong association with AEF (+) operators
      [4 (80 %) AEF (+) vs. 2 (10 %) AEF (-), p = 0.002]. There was a trend towards
      higher maximal RF energy setting in the posterior wall [47.4 + 7.6 AEF (+) vs.
      40.2 + 8 AEF (-), p = 0.09]. Other procedure parameters were similar.
      CONCLUSIONS: The reported prevalence of AEF among Canadian AF ablators is 0.07 %.
      AEF was associated with high mortality. The use of GA and non-brushing movements
      during posterior wall ablation were two factors associated with AEF.

PMID- 24317915
TI  - Dynamics of the history of photosynthesis research.
AB  - A personal view of the history of progress in photosynthesis research beginning
      in the seventeenth century and ending in 1992 is presented in a chart form. The
      350-year time span is divided arbitrarily into seven periods by the "development
      junctures", which are likened to bamboo joints. The tempo of progress is
      reflected in the duration of the periods, starting from over 200 years for Period
      I, which progressively shortens in subsequent periods. This brief introduction
      highlights some of the events to show the dynamic nature of the progress in
      photosynthesis research. 

PMID- 24317917
TI  - Initial experience of three-minute freeze cycles using the second-generation
      cryoballoon ablation: acute and short-term procedural outcomes.
AB  - BACKGROUND: The second-generation cryoballoon (CB-A) (Arctic Front Advance,
      Cryocath, Medtronic, MN, USA) might significantly improve procedural outcome with
      respect to the first-generation balloon. These technological improvements might
      also question the current recommendation of the need a 4-min freeze to achieve
      durable pulmonary vein isolation (PVI). OBJECTIVE: The main aim of the study was
      to analyze the procedural efficacy of a 3-min freeze-thaw cycles with the CB-A
      balloon in the terms of rates of acute PVI and 6-month outcome. METHODS: Patients
      having undergone CB-A for PAF or early persistent AF, with 3-min freeze-thaw
      cycles were consecutively included in our analysis. Acute procedural success was
      measured in terms of the rate of PVI. Short-term follow-up was evaluated by the
      means of 24-h Holters and clinical examinations at regular intervals. RESULTS:
      Fifty-two consecutive patients (35 male (67 %); mean age, 59.8 +/- 10.5) were
      included. Mean procedure and fluoroscopy times were 96 +/- 15 and 13.2 +/- 8.3
      min, respectively. Mean time from groin puncture to catheter extraction was 60.4
      +/- 20 min. After a mean of 1.5 freeze cycles per vein of 3 min in duration, all
      208 (100 %) PVs could be isolated with the CB-A. A total 192 (91 %) veins were
      isolated during the first freeze. At a mean of 5.7-month follow-up, 82 % of
      patients were free of AF. CONCLUSION: CB-A is effective in producing PVI by using
      3-min-duration freeze cycles. After a mean of 1.5 freeze per vein, freedom from
      AF was achieved in 82 % of patients at 6-month follow-up.

PMID- 24317918
TI  - Impact of pulmonary vein antrum isolation on left atrial size and function in
      patients with atrial fibrillation.
AB  - PURPOSE: The success of PVAI in eliminating AF has been proven; however, its
      impact on the LA remains uncertain. This study aimed to determine the impact of
      pulmonary vein antrum isolation (PVAI) on left atrial (LA) size and function in
      patients with atrial fibrillation (AF). METHODS: Consecutive patients with AF
      were included (n = 206). Magnetic resonance imaging (MRI) was performed before
      and after PVAI in all patients. A subgroup (n = 52) underwent delayed enhancement
      MRI. Maximal LA volume (LAVmax) and minimal LA volume (LAVmin) were assessed by
      Simpson's rule. LA function was determined by calculating LA ejection fraction
      (LA EF). LA fibrosis was manually encircled and summed in the region of interest.
      RESULTS: Single procedure success rate was 64 %. LAVmax decreased post-ablation
      in all patients (125.1 to 111.9 ml, p < 0.001). LAVmin only decreased in patients
      with a successful outcome post-ablation (65.6 to 58.8 ml, p < 0.001). As a
      result, LA EF only showed a marked reduction in patients with AF recurrences
      (42.7 % to 37.9 %, p < 0.001). Post-ablation LA fibrosis could be visualized in
      77 % of patients who underwent delayed enhancement MRI (mean amount 1.4 cm(3)).
      LA fibrosis showed no correlation with the decrease in LAVmax or LA EF.
      CONCLUSIONS: PVAI resulted in a reduction of LAVmax in all patients, indicating
      an effect of ablation induced fibrosis. LAVmin only decreased in patients with a
      successful outcome, indicating an effect of reverse atrial remodeling. As a
      result, LA function post-ablation was preserved in patients with a successful
      outcome and decreased in patients with AF recurrence.

PMID- 24317919
TI  - Radiation tolerance of contemporary implantable cardioverter-defibrillators.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are complex
      instruments using integrated circuit technology. Previous studies suggested risk
      to the device when exposed to a radiation environment. Little data is available
      on contemporary ICD systems. OBJECTIVES: The purpose of the present study was to
      assess the ability of contemporary ICD designs to resist the damaging effects of
      direct exposure to therapeutic doses of radiation. METHODS: Four contemporary
      ICDs and four legacy ICDs devices were exposed to escalating doses of photon
      irradiation (XRT) from a 6-MV linear accelerator. Escalating doses were
      administered over 8 days to a maximum cumulative dose of 131.11 Gy or
      catastrophic failure. RESULTS: Each legacy device had catastrophic failure
      following the 6th XRT session, characterized by failure to deliver shock therapy.
      All four contemporary devices remained fully functional following the 8th and
      final XRT session (P = 0.03). The cumulative, survived radiation dose was
      significantly different between the contemporary and legacy groups (131.11 vs.
      41.11 Gy, P = 0.01). Changes seen in the legacy devices were sudden and not
      anticipated by trends in prior sessions. CONCLUSION: The results of this study
      suggest that contemporary ICD designs may be more robust than earlier designs in
      a radiation environment.

PMID- 24317920
TI  - Are left-handers less violent?
AB  - Previous work has shown that left-handers are overrepresented among juvenile
      offenders. The present study was designed to test whether left-handers are also
      overrepresented among violent juvenile offenders. However, opposite to
      expectation, the results showed that left-handed offenders scored lower than
      right-handed offenders on the Violence Scale, a measure of the violence potential
      of offenses read from the legal record. The unexpected effect was consistent over
      four sex-ethnicity subgroups. Possible explanations concerned sex-handedness
      interactions and hemisphericity effects. 

PMID- 24317921
TI  - A comparison of normal and disturbed adolescent Offer Self-Image Questionnaire
      responses in an Irish cultural setting.
AB  - In an effort to gauge the overall usefulness of the Offer Self-Image
      Questionnaire (OSIQ) as a practical discriminator between clinically disturbed
      and normal Irish teenagers, the 11 scale scores and the mean of these scores for
      845 normal and 115 disturbed adolescents were computed and compared. The results
      show that the test does, in fact, distinguish disturbed adolescents from normals
      and, in particular, psychotic from both normal and other disturbed adolescents.
      We conclude that the test may have considerable potential on an individual
      clinical basis, provided suitable cultural norms are established. 

PMID- 24317922
TI  - Some thoughts on school size and its effects on adolescent development.
AB  - What do we know about the effects of school size on adolescent development? This
      article addresses this issue, based on a review of the available evidence. While
      this evidence is sketchy, it does offer three important hypotheses to guide our
      efforts to understand the human ecology of adolescence. First, school size
      matters, particularly to academically marginal students. Second, school size is
      not a simple linear effect. Rather, it involves a "threshold effect," so that
      increases in size above roughly 500 (in a secondary school) do not have an
      appreciable effect. Third, recent trends have "conspired" against youth by
      simultaneously producing larger schools - so that most schools are above the size
      threshold - and "forcing" ever larger numbers of academically marginal students
      into these secondary schools. This article explores these hypotheses and their
      significance for youth development. 

PMID- 24317923
TI  - The ideal love object: Structural and family sources.
AB  - We obtained preferences from 227 college students about the characteristics of
      their ideal love objects. We factor analyzed these separately for males and
      females and obtained both common and sex-specific factors. We then examined the
      relative contributions of a set of structural and family factors to the
      explanation of variance in each of the characteristics of the ideal love object.
      Results show that about one-third of the 58 characteristics have significant,
      though not high, amounts of variance explained by the predictors. The most
      important predictors were sex, religion, mother's marital happiness, and father's
      education. 

PMID- 24317924
TI  - The psychological impact of menarche: Integrative versus disruptive changes.
AB  - Ninety-four seventh- and eighth-grade girls, 49 premenarcheal and 45
      postmenarcheal, produced male and female human figure drawings. These drawings
      were scored for sexual differentiation, sexual identification, and anxiety
      related to aggression-hostility and insecurity-lability. Postmenarcheal girls
      were found to evidence greater sexual differentiation and clearer sexual
      identification than premenarcheal girls of the same age. Postmenarcheal girls did
      not differ from premenarcheal girls in level or class of anxiety, however.
      Together, these results provide evidence for viewing the impact of menarche as
      primarily integrative, rather than primarily disruptive. Implications of these
      findings for understanding menarche as a normal developmental crisis are
      explored. 

PMID- 24317925
TI  - Gender-role identity and psychological adjustment in adolescence.
AB  - The relationship between gender-role identity (traditional, androgynous, cross
      gender, and undifferentiated) and psychological adjustment among adolescents was
      examined. Hypotheses were derived from theories of gender-role identity
      development. One hundred and three high school students completed a measure of
      gender-role identity (the Bem Sex-Role Inventory) and four measures of adjustment
      (three Offer Self-Image scales and the Rosenberg Self-Esteem Scale). Findings
      indicate that traditional, androgynous, and cross-gender identities are each
      associated with some aspect of superior adjustment. Undifferentiated adolescents
      are poorly adjusted. When the independent contribution of masculinity,
      femininity, and gender-role identity to adjustment was assessed, masculinity and
      femininity had greater predictive power than gender-role identity. The
      relationship of findings to gender-role identity development is discussed. 

PMID- 24317926
TI  - Dominance hierarchies in groups of middle to late adolescent males.
AB  - Two cabin groups (N=5 and 6) of 14- to 17-year-old males were observed during a
      five-week camping session. Recorded were all instances of dyadic dominance
      behaviors occurring between group members in three behavior settings. Various
      group sociometric exercises and life history data were also available. Similar to
      previously studied early adolescent groups, the current middle and late
      adolescents formed a group dominance hierarchy that remained relatively stable
      during the camp session and in the behavior settings. In marked contrast to early
      adolescents, however, physical variables such as pubertal maturation, athletic
      ability, and physical fitness no longer predicted relative ranking among group
      members. Rather, individual variations in intelligence, creativity, crafts skill,
      cabin spirit, peer popularity, and camp experience predicted the group structure.
      Physical means of expressing dominance status were rare among the older
      adolescents. 

PMID- 24317928
TI  - Living in the cosmic frame.

PMID- 24317927
TI  - The inner lining of the reptilian brain: a heterogeneous cellular mosaic.
AB  - The ependymal layer is a preserved structure across vertebrates but its
      functional significance remains poorly understood. Modern studies emphasize the
      role played by radial glia (RG) as neurogenic progenitors. We speculated that the
      cells lining the prosencephalon ventricles of freshwater turtles may have
      retained key features of RG. To test this idea, we applied an approach that
      combined cellular, molecular, fine structural, and electrophysiological
      techniques. In the prosencephalon of juvenile turtles, we found cells with
      typical radial morphology that expressed four RG proteins: glial fibrillary
      acidic protein (GFAP), vimentin, S100/S100beta and brain lipid-binding protein
      (BLBP). Most of these cells expressed the transcription factor Sox2 but few co
      expressed Pax6. One type of RG had their somata close to the ventricle lumen and
      bear multiple cilia. A second class with cell bodies far from the lumen was
      usually uniciliated. RGs had low input resistances, passive properties and were
      coupled via Cx43 at the level of the cell bodies and radial processes. A third
      kind of cell was uncoupled, expressed neuronal proteins (HuC/D and NeuN) and
      fired spikes. The differential expression of HuC/D and NeuN together with their
      electrophysiological properties suggested various maturational stages. The
      occurrence of ependymal patches with a high density of 5-bromo-2-deoxyuridine
      (BrdU) labeled cells provides evidence of the proliferative capability of
      ependymal RG. Our data support the view that RG have retained key properties of
      neuroepithelial cells. The maintenance of proliferating RG could be also related
      with the outstanding endogenous ability of lower vertebrates for self-repair
      after injury.

PMID- 24317929
TI  - Ministry to families of chronically ill children.

PMID- 24317930
TI  - The humanness of two abrahams.

PMID- 24317931
TI  - James and the valence of human action.

PMID- 24317932
TI  - "...As the sparks fly upward".

PMID- 24317933
TI  - Anxiety and religious growth: A talmudic perspective.

PMID- 24317934
TI  - Beyond the norm: A speculative model of self-realization.

PMID- 24317935
TI  - Biochemical response to ursodeoxycholic acid predicts survival in a North
      American cohort of primary biliary cirrhosis patients.
AB  - BACKGROUND: Biochemical response to ursodeoxycholic acid among patients with
      primary biliary cirrhosis remains variable, and there is no agreement of an ideal
      model. Novel assessment of response coupled to histologic progression was
      recently defined by the Toronto criteria. We retrospectively assessed transplant
      free survival and clinical outcomes associated with ursodeoxycholic acid response
      to evaluate the Toronto criteria using a large North American cohort of PBC
      patients. METHODS: Three hundred and ninety-eight PBC patients from the Mayo
      Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid
      treatment and biochemical response per the Toronto criteria. Responders were
      defined by reduction in alkaline phosphatase to less than or equal to 1.67 times
      the upper normal limit by 2 years of treatment, whereas non-responders had
      alkaline phosphatase values greater than 1.67 times the upper normal limit.
      Probability of survival was estimated using the Kaplan-Meier method. RESULTS:
      Three hundred and two (76 %) patients were responders and 96 (24 %) were non
      responders. Significantly more non-responders developed adverse events related to
      chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001).
      Biochemical responders and early-stage disease at treatment start was associated
      with improved overall transplant-free survival compared to non-responders (HR
      1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment.
      CONCLUSIONS: The Toronto criteria are capable of identifying ursodeoxycholic acid
      treated primary biliary cirrhosis patients at risk of poor transplant-free
      survival and adverse clinical outcomes. Our data reveal that despite advanced
      disease at diagnosis, biochemical response per the Toronto criteria associates
      with improved overall transplant-free survival.

PMID- 24317936
TI  - Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained
      virological response to interferon: significance of lifelong periodic cancer
      screening for improving outcomes.
AB  - BACKGROUND: Due to advances in interferon (IFN) therapy for chronic hepatitis C,
      most elderly patients, and even many of those with advanced hepatic fibrosis, now
      achieve a sustained virological response (SVR). However, carcinogenesis remains
      problematic in these patients. Hence, we aimed to elucidate risk factors for
      hepatocarcinogenesis in SVR patients and to present an appropriate follow-up
      protocol for improving outcomes. METHODS: We retrospectively studied 562
      consecutive SVR patients for a median observation period of 4.8 years. RESULTS:
      Hepatocellular carcinoma was diagnosed in 31 patients (5.5%). Respective
      cumulative incidences were 3.1, 10.1, and 15.9% at 5, 10, and 15 years after
      completion of IFN therapy. The proportional hazards model identified moderate or
      advanced fibrosis stage, advanced age, habitual alcohol consumption, and alpha
      fetoprotein elevation as determinants of carcinogenesis, with hazard ratios of
      10.7 (p < 0.001), 4.1 (p < 0.01), 3.9 (p < 0.01), and 2.6 (p < 0.05),
      respectively. Carcinoma was diagnosed in 26% of patients more than 10 years after
      completion of IFN therapy. Unexpectedly, F2 fibrosis was detected in 42% of these
      patients. The 5-year survival rate was 93% in the patients who had received
      periodic cancer screening but only 60% in those who had not. CONCLUSION: We
      recommend that SVR patients be observed at 6-month intervals, at a minimum, to
      facilitate diagnosis at an early stage, for as long as possible after completion
      of therapy even if not at an advanced stage of fibrosis.

PMID- 24317938
TI  - Systematic studies of morphological changes of precision polyethylene.
AB  - The morphological changes of polyethylenes bearing precisely spaced "defects" are
      reviewed, focusing on the effects of defect frequency, size, and functionality on
      crystallization and crystalline structure. The precise defect interval is
      imparted through acyclic diene metathesis polymerization of structurally
      symmetric diene monomers. Studies have included structural characterization by
      differential scanning calorimetry, wide-angle X-ray scattering, small-angle X-ray
      scattering (SAXS), and infrared spectroscopy. The collective results are
      presented separately for functionalized polyethylenes and for those containing
      alkyl chain branches, as these two classes of polymers vary greatly in
      morphology. 

PMID- 24317937
TI  - Increase in colonic diverticulosis and diverticular hemorrhage in an aging
      society: lessons from a 9-year colonoscopic study of 28,192 patients in Japan.
AB  - PURPOSES: Colonoscopic evidence of epidemiological trends in diverticulosis and
      diverticular bleeding is scarce. We evaluated trends in diverticular disease and
      associated factors over 9 years. METHODS: Twenty-eight thousand one hundred
      ninety-two patients who underwent colonoscopy at an emergency hospital were
      reviewed from an electronic endoscopy database. Diverticula were classified as
      right-sided, left-sided, and bilateral types, and time trends in the proportion
      in diverticulosis, type, and diverticular bleeding were determined. Associations
      of age (<=39, 40-59, and >=60 years), sex, and year increase with disease and
      odds ratios were estimated using logistic regression. RESULTS: Diverticulosis was
      identified in 6,150 patients (20.3 %; mean age, 67.6 years) and was predominantly
      right-sided (48.0 %). Diverticular bleeding was found in 427 (1.5 %; mean age,
      69.7 years) and was predominantly bilateral (47.0 %). Proportion of colonic
      diverticulosis increased significantly (P < 0.01 for trend) from 66.0 %
      (1,424/2,157) in 2003 to 70.1 % (2,914/4,159) in 2011 and was associated (P <
      0.01) with an increased number of patients aged >=60 years. Proportion of
      diverticular bleeding increased significantly (P < 0.01 for trend) from 1.02 %
      (22/2,157) in 2003 to 1.67 % (69/4,159) in 2011 and was associated (P = 0.04)
      with an increased number of patients aged 40-59 years. Diverticulosis, right and
      bilateral type, and diverticular bleeding were independently associated with the
      9-year trend after adjustment by age and sex. CONCLUSIONS: Colonic diverticulosis
      and diverticular bleeding are prevalent and increasing in Japan. Given the
      significant association of age with this trend, both diseases can be expected to
      increase for decades to come.

PMID- 24317939
TI  - Cellulase in the kidney bean seedling.
AB  - Several parts of the 12-d-old seedling of Phaseolus vulgaris L. cv. Red Kidney
      were surveyed for cellulase activity. The laminar abscission zone and the
      cotyledon were highest in total cellulase while the petiole, stem, leaf and root
      had lesser activity. A portion of the cellulase from each tissue was associated
      with a membrane fraction which equilibrated on a sucrose density gradient at a
      density of 1.16 g/cm(3). Fortification of the buffer with 1 M NaCl was necessary
      for complete extraction of cellulase from all tissues. Ethylene treatment
      enhanced cellulase activity in the laminar abscission zone, the petiolar
      pulvinus, and somewhat in the stem, but not in the petiole nor the nodal region
      of the stem. Thus, those tissues which are target tissues for ethylene action
      also showed ethylene-enhanced cellulase activity. 

PMID- 24317940
TI  - Changes in ultrastructure and transcription induced by elevated temperature in
      Zea mays embryonic root cells.
AB  - A study has been made of the changes occurring in Zea mays kernels exposed to
      thermal shock at the 48th h of soaking at 16 degrees C, i.e., just before the
      protrusion of the root. Heat shock of 5 h at 46 degrees C temporarily inhibits
      the resumption of root growth and consequently retards the protrusion of the
      root. On the ultrastructural level, it is the nucleolus which undergoes the most
      dramatic changes. Total loss of the granular component occurs and new electron
      opaque corpuscles with diameters ranging from 80 to 140 nm appear. These
      corpuscles contain RNA and proteins. Microstereology shows that the vacuolation
      of the nucleolus is increased whereas its volume is decreased. Autoradiographical
      and biochemical studies of RNA synthesis show that the heat shock induces an
      inhibition of pre-rRNA synthesis. Only RNAs of low molecular weight are still
      synthesized. After 19 h of a return to 16 degrees C, the ultrastructural changes
      of the nucleolus are reversed. Nevertheless, increased nucleolar vacuolation
      persists up to that time. Exposure of maize kernels to 46 degrees C also produces
      the appearance of corpuscles in some areas of the cytoplasm and in the matrix of
      mitochondria. Disappearance of these structures is complete within 19 h, except
      in some mitochondria. 

PMID- 24317941
TI  - Effects of abscisic acid, gibberellic acid and fusicoccin on the transmembrane
      potential during the early phases of germination in radish (Raphanus sativus L.)
      seeds.
AB  - During germination, the transmembrane electric potential (PD) of cortical cells
      of the embryonal axis of radish seeds (Raphanus sativus L.) rises from-120 mV
      initially to a maximum of-150 mV after 5 h incubation, then falls again to stable
      values of around-120 mV. Treatments inhibiting germination block the transitory
      PD increase. Administration of uncoupling agents or low temperatures, during the
      process of germination, produces a marked fall of the PD transitory increase.
      Abscisic Acid has a parallel inhibitory effect on PD and germination, while
      fusicoccin produces a rise in both; administration of abscisic acid with
      fusicoccin inhibits germination, while the PD remains at the high levels given by
      fusicoccin. These results are discussed in relation to ion exchange at membrane
      level. 

PMID- 24317942
TI  - The effect of abscisic acid on sugar levels in seedlings of Phaseolus vulgaris L.
      cv. redland pioneer.
AB  - Abscisic acid (ABA) caused an increase in total-sugar and a 3-fold increase in
      reducing-sugar content in the roots of intact bean seedlings. The level of
      reducing sugars was also increased in the stem but total sugar levels remained
      unaffected by ABA. ABA also increased reducing-sugar content of the root in
      seedlings with cotyledons removed but in this case the reducing- and total-sugar
      contents of the leaf were reduced. However, ABA did not affect reducing- and
      total-sugar levels in excised bean root systems. The observed increase in sugar
      content of the root of intact bean seedlings appears to be the consequence of an
      ABA-induced stimulation of sugar transport from the shoot to the root. It is
      proposed that a relationship may exist between the effect of ABA on sugar
      transport and its effect on ion transport in excised root systems and in intact
      seedlings. 

PMID- 24317943
TI  - Phytochrome-mediated uptake of calcium in Mougeotia cells.
AB  - Ca(2+) is proposed to function as a messenger in such phytochrome-mediated
      responses as localized cell growth, intracellular movements, and control of
      plasma membrane properties. To test this hypothesis, the uptake of Ca(2+) in
      irradiated and non-irradiated regions of individual threads of the green alga
      Mougeotia was studied with the aid of (45)Ca(2+) and low temperature
      autoradiography: 10-20 cells within 40-60 cell-long threads were irradiated for
      up to 1 min, transferred to darkness for 3 to 10 min, submersed in a radioactive
      medium for 1 min, washed in an unlabelled medium for 30 min, and then
      autoradiographed at-80 degrees  C for several days.The autoradiographs show that
      those cells which had been pre-irradiated with red light did take up 2-10 times
      more Ca(2+) than the adjacent non-irradiated cells of the same thread. Cells pre
      irradiated with farred light or red light followed by far-red light showed no
      enhanced uptake of Ca(2+). These results might be interpreted to indicate,
      firstly, that phytochrome-Pfr is involved in the enhanced uptake of Ca(2+) and
      secondly, that the accumulation of radioactive Ca(2+) in red light irradiated
      cells is an expression of an increased intracellular concentration of Ca(2+).
      This interpretation is based on the data that (i) the dark interval between
      irradiation and labelling precluded the involvement of photosynthesis, (ii) the
      effect of red light was reversible with far-red light, and (iii) the accumulation
      of Ca(2+) persisted during the long wash-out period. We speculate, that the red
      light-enhanced accumulation of Ca(2+) in Mougeotia cells is caused by a Pfr
      mediated increase of the Ca-permeability of the plasma membrane, and perhaps by a
      Pfr-impeding of an active Ca(2+)-extrusion. 

PMID- 24317944
TI  - The role of microtubules and cell-wall deposition in elongation of regenerating
      protoplasts of Mougeotia.
AB  - Protoplasts of the filamentous green alga Mougeotia sp. are spherical when
      isolated and revert to their normal cylindrical cell shape during regeneration of
      a cell wall. Sections of protoplasts show that cortical microtubules are present
      at all times but examination of osmotically ruptured protoplasts by negative
      staining shows that the microtubules are initially free and become progressively
      cross-bridged to the plasma membrane during the first 3 h of protoplast culture.
      Cell-wall microfibrils areoobserved within 60 min when protoplasts are returned
      to growth medium; deposition of microfibrils that is predominantly transverse to
      the future axis of elongation is detectable after about 6 h of culture. When
      regenerating protoplasts are treated with either colchicine or isopropyl-N-phenyl
      carbamate, drugs which interfere with microtubule polymerization, they remain
      spherical and develop cell walls in which the microfibrils are randomly oriented.

PMID- 24317945
TI  - Biosynthesis of cell-wall polysaccharides in cultured carrot cells.
AB  - Biosynthesis of the cell wall in carrot cells (Daucus carota L.) cultured in a
      synthetic liquid medium was studied by measuring the incorporation of radioactive
      glucose and myo-inositol (MI). When the cells were fed with [(14)C]glucose in the
      presence of 0.01% MI, the label soon appeared in the neutral sugars in the cell
      wall but little radioactivity was found in the uronic-acid residues even after a
      prolonged incubation. On the other hand, radioactivity derived from [(3)H]MI was
      found to be distributed among uronic acids and pentoses but not in the hexose
      residues in the wall. The data indicate that MI is an important intermediate for
      the synthesis of acidic sugars in the wall of cultured carrot cells. 

PMID- 24317946
TI  - Biosynthesis of myo-inositol and its role as a precursor of cell-wall
      polysaccharides in suspension cultures of wild-carrot cells.
AB  - The biosynthesis of myo-inositol (MI) and its role as a precursor of cell-wall
      polysaccharides was studied in supension cultures of wild carrot (Daucus carota
      L.) cells. Suspension cultures, grown in the presence or absence of 2,4
      dichlorophenoxyacetic acid for 7 and 14d were incubated with [U-(14)C]glucose and
      [2-(3)H]MI in the presence of different concentrations of unlabeled MI. Synthesis
      of [(14)C]MI from [U-(14)C]glucose occurred under all conditions. The amount of
      MI synthesized from glucose was sharply reduced when 10 mM MI was provided in the
      medium. Substantial quantities of (3)H were incorporated in arabinose, xylose and
      galacturonic acid isolated and purified from the cell-wall polysaccharides of the
      cell cultures in various stages of growth or embryogenesis. No (3)H was present
      in the glucose or galactose units of cell-wall polysaccharides. At the four
      stages of growth and states of development of the carrot cultures used, the MI
      oxidation pathway contributed to the synthesis of pentosyl and galacturonosyl
      units of the cell wall. However, the data indicate that the contribution of the
      MI oxidation pathway to pentosyl and galacturonosyl units is small. 

PMID- 24317947
TI  - Endoplasmic reticulum in developing seeds of Vicia faba : A high voltage electron
      microscope study.
AB  - The changes in endoplasmic reticulum (ER) morphology during seed development have
      been followed using a thick section electron microscope technique. The tissues
      were stained with a zinc iodineosmium tetroxide complex which preferentially
      accumulated in the lumen between double membranes. Sections up to 2 MUm in
      thickness were examined in a high voltage electron microscope (HVEM) with tilt
      facility to produce stereo pairs. The micrographs from HVEM showed an increase in
      the extent of interconnecting tubular and cisternal ER during the protein
      deposition phase of seed maturation with subsequent degeneration of the cisternae
      to a reticular form during the final seed maturation phase. No evidence of
      cisternal ER vesicles was found, instead our work suggests that such structures
      are artefacts of thin sectioning with the so-called vesicles representing the
      interconnection of cisternal and tubular ER. The results are discussed with
      reference to the transport of storage protein from its site of synthesis, the
      rough cisternal ER, to that of accumulation, the vacuolar protein bodies. 

PMID- 24317948
TI  - Regulators of cell division in plant tissues : XXVII. Identification of an amino
      acid conjugate of 6-benzylaminopurine formed in Phaseolus vulgaris seedlings.
AB  - 6-[(3)H]Benzylaminopurine was supplied through the transpiration stream to de
      rooted Phaseolus vulgaris L. seedlings. The principal metabolite formed was
      identified as beta-(6-benzylaminopurin-9-yl)alanine by comparison with the
      synthetic compound. 

PMID- 24317949
TI  - Red/far-red modulation in vitro of enzyme activity in a membrane fraction from
      Phaseolus aureus.
AB  - In a membrane fraction isolated from hypocotyls of Phaseolus aureus Roxb. the
      activity of a number of enzymes was regulated by red and far-red irradiation in
      vitro, provided that the tissue received a brief red light treatment before
      extraction. Other enzymes showed no photoregulation. There were two types of
      photocontrol, neither of which could be detected in the solute fraction, nor in
      extracts from completely etiolated material. One (Type I) was a red/far-red
      reversible regulation of the rate of enzyme activity, depending on the light
      given (in vivo or in vitro) before the assay was begun. The second (Type II) was
      a promotion of enzyme activity by red or far-red light given during the assay.
      The action spectra for type II responses do not coincide with either the
      phytochrome absorption or difference spectra. However, the effectiveness of red
      and far-red was correlated with the Pfr/P ratio present at the beginning of the
      assay, such that far-red was more efficient at high Pfr/P and red at low Pfr/P
      ratios. All enzymes that were regulated involved ATP. In samples that showed
      enzyme regulation, small changes in fluorescence yield of tryptophan and the
      covalent probe "Fluram" (Roche) accompanied the photoconversion of phytochrome,
      but no fluorescence changes could be measured after briefly incubating the
      membrane fraction with ATP. The results indicate that light may affect the
      interaction of ATP with the membrane fraction. 

PMID- 24317950
TI  - Effect of aerobic and anaerobic conditions on the in vivo nitrate reductase assay
      in spinach leaves.
AB  - (15)N-labelled nitrate was used to show that nitrate reduction by leaf discs in
      darkness was suppressed by oxygen, whereas nitrite present within the cell could
      be reduced under aerobic dark conditions. In other experiments, unlabelled
      nitrite, allowed to accumulate in the tissue during the dark anaerobic reduction
      of nitrate was shown by chemical analysis to be metabolised during a subsequent
      dark aerobic period. Leaves of intact plants resembled incubated leaf discs in
      accumulating nitrite under anaerobic conditions. Nitrate, n-propanol and several
      respiratory inhibitors or uncouplers partly reversed the inhibitory effect of
      oxygen on nitrate reduction in leaf discs in the dark. Of these nitrate and
      propanol acted synergistically. Reversal was usually associated with inhibition
      of respiration but some concentrations of 2,4-dinitrophenol (DNP) and ioxynil
      reversed inhibition without affecting respiratory rates. Respiratory inhibitors
      and uncouplers stimulated nitrate reduction in the anaerobic in vivo assay i.e.
      in conditions where the respiratory process is non-functional. Freezing and
      thawing leaf discs diminished but did not eliminate the sensitivity of nitrate
      reduction to oxygen inhibition. 

PMID- 24317951
TI  - Formation of lipid-linked mono- and oligosaccharides from GDP-mannose by castor
      bean endosperm homogenates.
AB  - A crude organelle preparation from germinating castor bean endosperm catalysed
      the incorporation of mannose from GDP[(14)C]mannose into acid-labile mannolipids.
      Solubility and chromatographic properties have identified the most rapidly
      synthesized products as mannosyl-phosphoryl-polyisoprenol, while the more polar
      lipid formed was shown to contain oligosaccharide. Little radioactivity from
      GDP[(14)C]mannose accumulated in insoluble product in the cell-free system, but
      supplying GDP[(14)C]mannose to intact endosperm tissue has shown that the major
      incorporation product in vivo is glycoprotein. This product was readily
      solubilized by either pronase or sodium dodecyl sulphate treatment suggesting it
      was membrane bound glycoprotein. Incorporation of mannose into mannosyl
      phosphoryl-polyisoprenol during the cell-free assay was stimulated by the
      addition of dolichol monophosphate. This enzymic activity was optimal at pH 7.5
      and in the presence of 10 mM Mg(2+). The Km for GDP-mannose was estimated to be
      5*10(-7) M. Cellular mannosyl transferase activity changed markedly during early
      post-germinative growth; from being absent in the dry seed, enzyme activity
      increased to peak between the second and third days of growth and subsequently
      declined. 

PMID- 24317952
TI  - The identification of gibberellins in immature seeds of Vicia faba, and some
      chemotaxonomic considerations.
AB  - GA17, GA19, GA20, GA29, GA44 and 13-hydroxy-GA12, now named GA53, were identified
      by GC-MS in immature seeds of Vicia faba (broad bean). Also identified were a GA
      catabolite, two polyhydroxykauranoic acids, and abscisic, phaseic and
      dihydrophaseic acids. The GAs of Vicia are hydroxylated at C-13, in common with
      those of other legumes. However the GAs of Vicia are not hydroxylated at C-3, nor
      do they appear to be readily conjugated. In these respects Vicia resembles Pisum,
      another member of the tribe Viciae. Vicia differs from Phaseolus and Vigna, of
      the tribe Phaseoleae, in both these respects. 

PMID- 24317953
TI  - An assessment of auxin-promoted transport in decapitated stems and whole shoots
      of Phaseolus vulgaris L.
AB  - (14)C-photosynthate transfer in decapitated stems of P. vulgaris plants, treated
      with IAA (indol-3yl-acetic acid), appeared, as ascertained by
      microautoradiography, to be restricted to cells of sieve-element appearance. The
      IAA-induced promotion of photosynthate transport was found not to depend on any
      artifacts caused by the decapitation procedure. Rather, decapitation primarily
      served the purpose of removing photosynthate sources above the point of hormone
      application which otherwise suppressed the expression of the IAA effect on
      acropetal photosynthate transport. Furthermore, by manipulating stem levels of
      endogenous auxins with the inhibitor of polar auxin transport, 1-(2(1)
      carboxyphenyl)-3-phenylpropane-1,3-dione (ACP1.55), evidence was obtained
      indicating that photosynthate transfer to the shoot apex depended, at least in
      part, on endogenous levels of auxins at site(s) remote from the apical sink (i.e.
      shoot apex). 

PMID- 24317954
TI  - A lovastatin-elicited genetic program inhibits M2 macrophage polarization and
      enhances T cell infiltration into spontaneous mouse mammary tumors.
AB  - Beyond their ability to inhibit cholesterol biosynthesis, the statins have
      pleiotropic effects that include anti-inflammatory and immunomodulatory
      activities. Statins could have clinical utility, alone or in combination with
      other chemotherapeutics, in the treatment of cancer. The mechanisms that underlie
      the anti-tumor activity of the statins are nonetheless poorly defined. No studies
      have analyzed how they alter the tumor-associated leukocyte infiltrate, a central
      factor that influences tumor stroma and cancer evolution. Here we used HER2/neu
      transgenic (Tg-neu) mice to analyze the effect of lovastatin (Lov) on the
      inflammatory reaction of spontaneous mammary tumors. Lov treatment of tumor
      bearing Tg-neu mice did not alter growth of established tumors, but significantly
      reduced the number of new oncogenic lesions in these mice. Moreover, Lov
      inhibited the growth of newly implanted Tg-neu tumors in immunocompetent but not
      in immunodeficient mice. We found that Lov enhanced tumor infiltration by
      effector T cells, and reduced the number of immunosuppressive and pro-angiogenic
      M2-like tumor-associated macrophages (TAM). Concomitantly, the drug improved the
      structure and function of the tumor vasculature, measured as enhanced tumor
      oxygenation and penetration of cytotoxic drugs. Microarray analysis identified a
      Lov-elicited genetic program in Tg-neu tumors that might explain these effects;
      we observed Lov-induced downregulation of placental growth factor, which triggers
      aberrant angiogenesis and M2-like TAM polarization. Our results identify a role
      for lovastatin in the shaping and re-education of the inflammatory infiltrate in
      tumors, with functional consequences in angiogenesis and antitumor immunity.

PMID- 24317955
TI  - Barriers and facilitators to engagement and retention in care among transgender
      women living with human immunodeficiency virus.
AB  - BACKGROUND: Transgender women have 49 times the odds of human immunodeficiency
      virus (HIV) infection compared to other groups, yet they are disproportionately
      underserved by current treatment efforts. PURPOSE: This study aimed to examine
      culturally unique barriers and facilitators to engagement and retention in HIV
      care and strengthen efforts to mitigate health disparities, guided by the Models
      of Gender Affirmation and Health Care Empowerment. METHODS: Through 20 interviews
      and five focus groups (n = 38), transgender women living with HIV discussed their
      experiences and life contexts of engagement in and adherence to HIV care and
      treatment. RESULTS: Our participants faced substantial challenges to adhering to
      HIV care and treatment, including avoidance of healthcare due to stigma and past
      negative experiences, prioritization of hormone therapy, and concerns about
      adverse interactions between antiretroviral treatment for HIV and hormone
      therapy. Receiving culturally competent, transgender-sensitive healthcare was a
      powerful facilitator of healthcare empowerment. CONCLUSIONS: Recommendations are
      offered to inform intervention research and guide providers, emphasizing gender
      affirming HIV care that integrates transition-related healthcare needs.

PMID- 24317956
TI  - An indirect approach to the measurement of nutrient-specific perceptions of food
      healthiness.
AB  - BACKGROUND: Enhancing our understanding of food-related perceptions is critical
      to assist those with eating- and weight-related problems. PURPOSE: This study
      investigated normative and person-specific aspects of perceived food healthiness
      in terms of nutritional characteristics and the relevance of nutritional
      knowledge to perceived healthiness. METHODS: Two hundred sixty-three
      undergraduate women judged the healthiness of 104 foods and completed nutrient
      knowledge tasks. Multilevel modeling estimated average and person-specific
      reliance on and knowledge about nutrients. RESULTS: Participants relied
      substantially on fat and fiber, moderately on sugar, and minimally on protein.
      Disordered eating symptoms moderately predicted greater reliance on fat.
      Nutritional knowledge was highest for sugar and lowest for fiber. Nutritional
      knowledge and utilization were unrelated. CONCLUSIONS: Public health campaigns
      should educate college-aged women further on the health consequences of sugar and
      protein consumption. Explicit knowledge of nutrients may not be prioritized when
      judging food healthiness.

PMID- 24317957
TI  - Static biofilm removal around ultrasonic tips in vitro.
AB  - OBJECTIVES: This study aims to investigate the biofilm removal capacity of two
      ultrasonic tips under standardized conditions using a multi-species biofilm
      model. METHODS: Six-species biofilms were grown on hydroxyapatite discs for 64.5
      h and were treated for 15 s with a standardized load of 40 g with a piezoelectric
      or magnetostrictive device. Tips were applied either with the tip end or with the
      side facing downwards. Detached bacteria were determined in the supernatant and
      colony-forming units (CFUs) counted after 72 h of incubation. Untreated specimens
      served as controls. Moreover, the biofilms remaining on the hydroxyapatite
      surface after treatment were stained using the Live/Dead stain, and the pattern
      of their detachment was assessed by confocal laser scanning microscopy (CLSM).
      RESULTS: As compared to the untreated control, it was found that only a side
      application of the magnetostrictive device was able to remove efficiently the
      biofilm. In contrast, its tip application as well as both applications of the
      piezoelectric device removed significantly less bacteria from the biofilm
      structure. These findings were corroborated by CLSM observation. CONCLUSION: Both
      ultrasonic tips under investigations led to bacterial detachment, but the action
      mode as well as the tip configuration and adaptation appeared to be influenced by
      the biofilm removal effectiveness. CLINICAL RELEVANCE: Biofilm removal remains a
      main goal of ultrasonic debridement. This should be reflected in respective
      laboratory investigations. The presented combination of methods applied on a
      multi-species biofilm model in vitro allows the evaluation of the effectiveness
      of different ultrasonic scaler applications.

PMID- 24317958
TI  - The effect of four different irrigation systems in the removal of a root canal
      sealer.
AB  - OBJECTIVES: The aim of this study was to compare the efficiency of sonic,
      ultrasonic, and hydrodynamic devices in the removal of a root canal sealer from
      the surface and from simulated irregularities of root canals. MATERIALS AND
      METHODS: Fifty-three root canals with two standardized grooves in the apical and
      coronal parts of longitudinally split roots were covered with AH Plus root canal
      sealer. Compared were the effects of (control) syringe irrigation, (1)
      CanalBrush, (2) passive ultrasonic irrigation, (3) EndoActivator, and (4)
      RinsEndo on the removal of the sealer. The specimens were divided into four
      groups (N = 12) and one control group (N = 5) via randomization. The amount of
      remaining sealer in the root canal irregularities was evaluated under a
      microscope using a 4-grade scoring system, whereas the remaining sealer on the
      root canal surface was evaluated with a 7-grade scoring system. RESULTS: Passive
      ultrasonic irrigation is more effective than the other tested irrigation systems
      or syringe irrigation in removing sealer from root canal walls (p < 0.01). None
      of the techniques had a significant effect on cleaning the lateral grooves.
      CONCLUSIONS: Within the limitations of this study protocol ultrasonic irrigation
      shows a superior effect on sealer removal from the root canal surface during
      endodontic retreatment. Cleaning of lateral grooves seems not to be possible with
      one of the techniques investigated. CLINICAL RELEVANCE: Incomplete removal of
      root canal sealer during re-treatment may cause treatment failure. Passive
      Ultrasonic irrigation seems to be the most effective system to remove sealer from
      a root canal.

PMID- 24317959
TI  - Test-retest reliability of the Orebro Musculoskeletal Pain Screening
      Questionnaire and the Situational Pain Scale in patients with chronic low back
      pain.
AB  - OBJECTIVE: To determine the test-retest reliability of the Orebro Musculoskeletal
      Pain Screening Questionnaire (OMPSQ) and of the Situational Pain Scale (SPS) in
      patients with chronic low back pain (CLBP). METHODS: CLBP patients (n = 30) who
      were capable of reading French completed the OMPSQ and the SPS twice with a 1
      week interval in one rehabilitation centre in French-speaking Switzerland. To
      study the test-retest reliability, we calculated intraclass correlation
      coefficients (ICCs) for the reliability of the overall scores of the two
      questionnaires. RESULTS: The ICC for the OMPSQ overall score was 0.89 (95%
      confidence interval [CI] 0.79-0.95). For the overall scores of the SPS, the ICC
      was 0.87 (95% CI 0.74-0.93). The standard error of the mean, expressed as
      percentage of the mean, was 6.6% for the SPS and 10% for the OMPSQ. CONCLUSIONS:
      The reproducibility of these two questionnaires in a sample of patients with CLBP
      is considered good at the overall score level. The French translation of the
      OMPSQ could be considered as a tool to examine the evolution of psychosocial
      factors.

PMID- 24317960
TI  - Associative recognition and the list strength paradigm.
AB  - When a subset of list items is strengthened, the discriminability of the
      nonstrengthened items is unaffected. This regularity has been dubbed the null
      list strength effect (LSE), and despite its many replications in item
      recognition, little research has investigated whether an LSE occurs in
      associative recognition. We conducted two experiments in which a set of pairs
      were studied once and a set of interference pairs were studied either once (pure
      weak-list condition) or four times (mixed-list condition). Equivalent levels of
      performance for the nonstrengthened pairs were observed in both the pure-weak and
      mixed conditions using both yes-no and two-alternative forced choice testing.
      Additionally, equivalent false alarm rates were observed between rearranged pairs
      composed of weak and strong items. Both sets of results were found to be
      consistent with a matrix model that has no overlap among its item
      representations. 

PMID- 24317961
TI  - Biochemical characterisation of the Li locus, which controls the activity of the
      cyanogenic beta-glucosidase in Trifolium repens L.
AB  - The cyanogenic beta-glucosidase (linamarase) was purified from white clover leaf
      tissue. The enzyme is a homodimer with a molecular weight of 105 300-103 400
      daltons estimated from molecular exclusion chromatography. The effect of buffer
      ions on the pH optimum and charge properties of the enzyme are presented. A
      combination of molecular exclusion chromatography and CM cellulose ion exchange
      chromatography purified linamarase 16 fold to a single 62 000 dalton polypeptide
      on SDS polyacrylamide gel electrophoresis. This polypeptide represented about 5%
      of the total soluble leaf protein and can be seen as a prominent band in SDS
      polyacrylamide gel electrophoresis of crude leaf extracts from Li Li plants.
      Screening backcross progeny showed that extracts from li li plants, which have no
      linamarase activity, lack this 62 000 dalton polypeptide. Linamarase is the major
      glycoprotein in white clover leaf extracts which binds to Concanavalin A
      Sepharose. 

PMID- 24317962
TI  - The chloroplast DNAs of flax genotrophs.
AB  - The chloroplast DNA of L. usitatissimum var. "Stormont Cirrus" has been mapped
      with respect to the recognition sites for the enzymes SalP1, Sst1 and SalG1. It
      is a circular molecule of about 160 kilobasepairs, with an inverted repeat
      containing the rDNA. Comparisons between chloroplast DNA of uninduced and induced
      flax genotrophs show there to be no major structural differences. 

PMID- 24317963
TI  - Gibberellic acid and abscisic acid modulate protein synthesis and mRNA levels in
      barley aleurone layers.
AB  - Using in vivo pulse labeling, changes in the pattern of protein synthesis were
      detected in isolated barley aleurone layers treated with fibberellic acid (GA3).
      GA3 greatly altered the relative rates of synthesis of many polypeptides,
      increasing some, notably alpha-amylase, and decreasing others. alpha-Amylase
      synthesis increased until it was the major product (over 60%) of protein
      synthesis after 24h. The pulse-labeled pattern of secreted polypeptides was also
      changed by GA3. There was the expected increase in alpha-amylase together with a
      number of other polypeptides but there was reduced secretion of several
      polypeptides also.Cell-free translation of RNA isolated from control and hormone
      treated tissues was used to measure changes in mRNA levels. GA3 caused many
      changes, particularly in the level of mRNA for alpha-amylase. In vitro
      synthesized alpha-amylase, identified by immunoaffinity chromatography, had an Mr
      of 46 000. This polypeptide was partially processed to a polypeptide with Mr 44
      000 by the addition of dog pancreas membranes to the in vivo translation mixture.
      The level of mRNA for alpha-amylase began to increase 2-4 h after GA3 was added
      and reached a maximum level of about 20% of total mRNA after 16 h. Thus after 16
      h, the synthesis of alpha-amylase as a proportion of total protein synthesis,
      continued to increase while the level of its mRNA as a proportion of total mRNA
      remained constant. These results indicate that protein synthesis was modified
      more extensively than we can account for by changes in mRNA.Abscisic acid (ABA)
      reversed all of the effects of GA3 on protein synthesis and mRNA levels. It also
      promoted synthesis of a small number of new polypeptides and increased the level
      of some mRNAs. GA3 reversed the accumulation of ABA-promoted mRNAs. Although, ABA
      strongly suppressed the increase in the level of translatable mRNA for alpha
      amylase, there was an even stronger inhibition of enzyme synthesis and
      accumulation.We conclude that both GA3 and ABA regulate protein synthesis both
      positively and negatively in aleurone cells largely by regulating levels of mRNA
      and in the case of alpha-amylase, possibly also by changing the efficiency of
      translation of its mRNA. 

PMID- 24317964
TI  - Double infection of tobacco plants by two complementing octopine T-region mutants
      of Agrobacterium tumefaciens.
AB  - The molecular basis of complementation by a mixture of two different types of
      octopine T-region mutants (LBA4060 and LBA4210) was studied. Six randomly chosen
      cellular clones derived from a tumor obtained after mixed infection were analyzed
      for their T-DNA content via Southern blot hybridization. The clones appeared to
      contain T-DNA that originated from each of both mutants, indicating that they
      developed from doubly infected single cells. Genetic complementation, therefore,
      might explain at least in part the observed complementation phenomenon. However,
      complementation as a result of cross-feeding between separately transformed cells
      could not be excluded. Following protoplast isolation, small aggregates might
      have formed that developed into the clones analyzed. 

PMID- 24317965
TI  - In vitro synthesis of the Bowman-Birk and related soybean protease inhibitors.
AB  - Poly (A)(+) RNAs from immature soybean seeds were size fractionated in denaturing
      sucrose gradients to identify mRNA that directs the cell-free synthesis of the
      Bowman-Birk protease inhibitor and the related inhibitors PI I-IV. Polypeptides
      synthesized in vitro were labeled with ((35)S)-cysteine and ((3)H)-serine and
      detected by immunoprecipitation with anti Bowman-Birk and anti PI I-IV sera.
      Immunoprecipitates of the translation products comigrated on SDS-polyacrylamide
      gels with the dimeric or trimeric aggregates of the authentic inhibitor proteins,
      which self-associate under certain conditions. Further evidence that these
      immunoprecipitates contained authentic polypeptides corresponding to the Bowman
      Birk or PI IV inhibitor was shown by sequential amino acid analyses of peptides
      generated by cleavage with cyanogen bromide. 

PMID- 24317966
TI  - Conservation of ribosomal RNA gene arrangement in the mitochondrial DNA of
      angiosperms.
AB  - In six different angiosperms, mitochondrial genes for 18S and 5S rRNAs were found
      to be closely linked but distant from mitochondrial 26S rRNA genes. 

PMID- 24317968
TI  - Musculoskeletal changes after 1 year of exercise in older breast cancer
      survivors.
AB  - INTRODUCTION: We have previously reported that 1 year of supervised resistance +
      impact training stopped bone loss and built muscle strength in older breast
      cancer survivors. The purpose of this study was to determine whether these
      benefits persisted 1 year after completion of the intervention. METHODS: Sixty
      seven women from the original trial completed baseline and post-intervention body
      composition and muscle strength tests, and 44 women were available 1 year later
      for follow-up assessments. Bone mineral density (grams per square centimeter) of
      the hip and spine, muscle mass (kilograms), and fat mass (kilograms) were
      measured by dual-energy X-ray absorptiometry and maximal upper and lower body
      strength were measured by one-repetition maximum tests (kilograms). We compared
      between group changes across baseline (pre-intervention), 1 (post-intervention),
      and 2 years (1 year follow up) on study outcomes using repeated-measures analysis
      of covariance, adjusting for age. RESULTS: Significant group by time interactions
      were found for spine bone mineral density (BMD) (p < 0.01) and lower body muscle
      strength (p < 0.05), with a trend for upper body muscle strength (p = 0.05).
      Spine BMD remained stable across intervention and follow-up periods in exercisers
      compared with continuous losses in controls across 1- and 2-year periods. In
      contrast, lower body strength increased in exercisers across the intervention,
      but decreased to near-baseline levels during follow-up compared with no change
      over either time period in controls. CONCLUSIONS: Our data suggest that spine BMD
      can be preserved in older breast cancer survivors even after formal exercise
      training stops; however, muscle strength is not similarly maintained and may
      require continued participation in a supervised exercise program. IMPLICATIONS
      FOR CANCER SURVIVORS: Exercise programs aimed at improving musculoskeletal health
      should be considered in the long-term care plan for breast cancer survivors.

PMID- 24317969
TI  - Fostering coordinated survivorship care in breast cancer: who is lost to follow
      up?
AB  - INTRODUCTION: Increasing numbers of cancer survivors and the recognition of their
      needs beyond recurrence surveillance are stretching resources at many cancer
      centers. Sometimes, patients solely follow up with providers other than the
      oncologist without coordinated care transfer plans. This study examines factors
      associated with transfer of breast cancer survivorship care outside one large
      cancer center. METHODS: Records on women with breast cancer diagnosed between
      July 1, 1997 and March 31, 2010 were linked to billing data through March 31,
      2012 to identify the details of last oncology follow-up. A patient was classified
      as having transferred care outside the center if there was no oncology visit for
      more than 2 years. Clinical and pathologic characteristics were examined in a
      multivariate proportional hazards model to identify factors associated with
      transfer of care. RESULTS: Of 3,924 women with breast cancer, 858 (21.9%)
      transferred care outside of our institution, 18 and 36% at 5 and 10 years,
      respectively. Factors independently associated with transfer of care were age at
      diagnosis (unit increase 1.01/year age), stage IIA (HR 1.30, p = 0.02), longer
      driving distance to the cancer center (HR 1.65, p < 0.01), having had a cancer
      recurrence (HR 0.15 p < 0.01), and last visit in a medical oncology versus
      surgical oncology clinic (HR 0.32 p < 0.01). CONCLUSIONS: Many patients with
      breast cancer do not continue oncology follow-up after treatment. Cancer programs
      should develop mechanisms to assist patients with care transfer and assure
      coordinated transfer to other providers to improve continuity of care.
      IMPLICATIONS FOR CANCER SURVIVORS: The results of this study will help the cancer
      centers identify the population of patients that are most likely to transfer care
      or become lost to follow up. Prospectively, identifying patients who may be more
      likely to transfer care will offer opportunities to effectively coordinate
      posttreatment surveillance with primary care.

PMID- 24317970
TI  - Measurement of physical activity in cancer survivors: a validity study.
AB  - PURPOSE: The purpose of the study was to validate the Taiwanese version of the
      Physical Activity Scale for the Elderly (PASE-T) and to assess physical activity
      in Taiwanese cancer survivors. METHODS: One hundred twenty-seven cancer survivors
      participated in this study. Instruments consisted of the PASE-T, the Taiwanese
      version of the MD Anderson Symptom Inventory (MDASI-T), Karnofsky performance
      status (KPS), and actigraph. Reliability was assessed by calculating the test
      retest reliability. The validity was assessed by the content validity, criterion
      related validity, convergent validity, and known-group validity. RESULTS: The
      test-retest reliability of PASE-T was 0.90 over a 2-week interval, based on a
      sample of 30 patients. The content validity index was very acceptable at 0.91.
      Convergent validity was demonstrated by its significant association with MDASI-T
      scores (symptom severity: r = -0.23, p = 0.001; symptom interference: r = -0.21,
      p = 0.001) and KPS scores (r = 0.59, p < 0.001). Criterion-related validity was
      established by a significant relationship to the actigraph total counts per
      minute (r = 0.64, p < 0.001). Known-group validity was established by its ability
      to detect significant differences according to a patient's performance status.
      Moreover, KPS (beta = 0.37), fatigue (beta = -0.32), and age (beta = -0.20) were
      significant predictors of physical activity (R(2) = 0.46). CONCLUSIONS: The PASE
      T is a reliable and valid instrument for measurement of physical activity among
      cancer survivors in Taiwan. IMPLICATION FOR CANCER SURVIVORS: This scale could be
      a useful measure of physical activity in cancer survivors and subsequently
      facilitate the quality of oncology care.

PMID- 24317971
TI  - Evaluation of traditional and novel measures of cardiac function to detect
      anthracycline-induced cardiotoxicity in survivors of childhood cancer.
AB  - PURPOSE: Cardiovascular disease is the leading noncancer cause of death among
      survivors of childhood cancer. Ejection fraction (EF) and fractional shortening
      (FS) are common echocardiographic measures of cardiac function, but newer imaging
      modalities may provide additional information about preclinical disease. This
      study aimed to evaluate these modalities in detection of anthracycline-induced
      cardiac toxicity. METHODS: We compared mean radial displacement, EF, and FS among
      17 adult survivors of childhood cancer exposed to >= 300 mg/m(2) of
      anthracyclines to 17 age- and sex-matched healthy controls. Survivors with a
      history of cardiac-directed radiation, diabetes, or heart disease were excluded.
      RESULTS: Survivors (35% male), mostly with history of treatment for a solid
      tumor, had a median age at diagnosis of 15 years (1-20) and 27 years (18-50) at
      evaluation. Median anthracycline exposure was 440 (range 300-645) mg/m(2). FS
      (35.5 vs. 39.6%, p < 0.01) and radial displacement (5.6 vs. 6.7 mm, p = 0.02)
      were significantly lower in survivors compared to controls, respectively.
      Although the mean EF was lower in survivors versus controls (55.4 vs. 59.7%), it
      was not statistically significant (p = 0.057). All echocardiographic measures
      were inversely associated with anthracycline dose, though radial displacement was
      no longer significantly correlated with anthracycline dose after controlling for
      survival time (p = 0.07), while EF remained correlated (p = 0.003). IMPLICATIONS
      FOR CANCER SURVIVORS: Radial displacement, EF, and FS are lower in childhood
      cancer survivors compared to controls. In this study, radial displacement added
      no new information beyond the traditional measures, but clinical utility remains
      undetermined and requires further longitudinal study.

PMID- 24317972
TI  - The effect of meeting physical activity guidelines for cancer survivors on
      quality of life following radical prostatectomy for prostate cancer.
AB  - PURPOSE: Recent literature has shown that preoperative physical activity (PA) can
      positively influence surgical outcomes. It is unknown whether the effect of
      meeting PA guidelines for cancer survivors can impact quality of life following
      radical prostatectomy for prostate cancer. METHODS: We reviewed our institutional
      database of prostate cancer outcomes and included patients that underwent radical
      prostatectomy and completed the Godin-Shephard Leisure Time Exercise
      Questionnaire (GLTEQ), the Patient-Oriented Prostate Utility Scale (PORPUS), the
      International Prostate Symptom Score (IPSS), and the five-item International
      Index of Erectile Function (IIEF). Participants were categorized as meeting or
      not meeting the American College of Sports Medicine physical activity guidelines
      for cancer survivors (150 min of moderate intensity or 75 min of vigorous
      intensity PA per week). Radical prostatectomy outcomes were measured
      preoperatively and at 6 and 26-weeks postoperatively. RESULTS: From June 2008 to
      August 2012, 509 men underwent curative, nerve-sparing radical prostatectomy for
      prostate cancer and completed the GLTEQ, of whom 46% met the PA guidelines. Prior
      to surgery, men that met the PA guidelines reported higher quality of life (p <
      0.001) and erectile function (p = 0.049) than men that did not meet the
      guidelines. Quality of life at all postoperative timepoints was higher for men
      that met the PA guidelines after adjusting for age, preoperative body mass index,
      and surgical approach (p = 0.02). Men that met the PA guidelines were 19% less
      likely to be incontinent at 6 weeks postoperatively (p = 0.028). CONCLUSION: PA
      volume may be a useful marker at predicting postoperative recovery of quality of
      life and urinary incontinence following radical prostatectomy. IMPLICATIONS FOR
      CANCER SURVIVORS: Cancer survivors should be encouraged to meet PA guidelines
      prior to surgery in an effort to attenuate the decline in HRQOL and facilitate
      recovery.

PMID- 24317973
TI  - Complete DNA sequence of Kuraishia capsulata illustrates novel genomic features
      among budding yeasts (Saccharomycotina).
AB  - The numerous yeast genome sequences presently available provide a rich source of
      information for functional as well as evolutionary genomics but unequally cover
      the large phylogenetic diversity of extant yeasts. We present here the complete
      sequence of the nuclear genome of the haploid-type strain of Kuraishia capsulata
      (CBS1993(T)), a nitrate-assimilating Saccharomycetales of uncertain taxonomy,
      isolated from tunnels of insect larvae underneath coniferous barks and
      characterized by its copious production of extracellular polysaccharides. The
      sequence is composed of seven scaffolds, one per chromosome, totaling 11.4 Mb and
      containing 6,029 protein-coding genes, ~13.5% of which being interrupted by
      introns. This GC-rich yeast genome (45.7%) appears phylogenetically related with
      the few other nitrate-assimilating yeasts sequenced so far, Ogataea polymorpha,
      O. parapolymorpha, and Dekkera bruxellensis, with which it shares a very reduced
      number of tRNA genes, a novel tRNA sparing strategy, and a common nitrate
      assimilation cluster, three specific features to this group of yeasts.
      Centromeres were recognized in GC-poor troughs of each scaffold. The strain bears
      MAT alpha genes at a single MAT locus and presents a significant degree of
      conservation with Saccharomyces cerevisiae genes, suggesting that it can perform
      sexual cycles in nature, although genes involved in meiosis were not all
      recognized. The complete absence of conservation of synteny between K. capsulata
      and any other yeast genome described so far, including the three other nitrate
      assimilating species, validates the interest of this species for long-range
      evolutionary genomic studies among Saccharomycotina yeasts.

PMID- 24317974
TI  - Shared subgenome dominance following polyploidization explains grass genome
      evolutionary plasticity from a seven protochromosome ancestor with 16K
      protogenes.
AB  - Modern plant genomes are diploidized paleopolyploids. We revisited grass genome
      paleohistory in response to the diploidization process through a detailed
      investigation of the evolutionary fate of duplicated blocks. Ancestrally
      duplicated genes can be conserved, deleted, and shuffled, defining dominant (bias
      toward duplicate retention) and sensitive (bias toward duplicate erosion)
      chromosomal fragments. We propose a new grass genome paleohistory deriving from
      an ancestral karyotype structured in seven protochromosomes containing 16,464
      protogenes and following evolutionary rules where 1) ancestral shared
      polyploidizations shaped conserved dominant (D) and sensitive (S) subgenomes, 2)
      subgenome dominance is revealed by both gene deletion and shuffling from the S
      blocks, 3) duplicate deletion/movement may have been mediated by single-/double
      stranded illegitimate recombination mechanisms, 4) modern genomes arose through
      centromeric fusion of protochromosomes, leading to functional monocentric
      neochromosomes, 5) the fusion of two dominant blocks leads to supradominant
      neochromosomes (D + D = D) with higher ancestral gene retention compared with D +
      S = D (i.e., fusion of blocks with opposite sensitivity) or even S + S = S (i.e.,
      fusion of two sensitive ancestral blocks). A new user-friendly online tool named
      "PlantSyntenyViewer," available at http://urgi.versailles.inra.fr/synteny-cereal,
      presents the refined comparative genomics data. 

PMID- 24317976
TI  - Earlier researches on the mechanism of oxygen evolution: A personal account.
AB  - A brief overview is given of the research which led to the discovery of the
      period-4 oscillations of the flash-induced oxygen production and which is the
      basis of the generally accepted Kok's model for water splitting and oxygen
      evolution.In this paper I discuss the earlier work of the groups of Robert
      Emerson, James Franck, C. P. Whittingham, and myself in relation to the
      development of new techniques for the detection of photosynthetic oxygen
      evolution. Also discussed are various hypotheses and speculations related to the
      concept of a priming photoreaction which is required for oxygen evolution.
      Finally, I discuss my long scientific collaboration with Bessel Kok which led to
      the elaboration by Kok of the classical model in which the formation of oxygen
      requires the sequential accumulation of four positive charges on the same
      photochemical center. 

PMID- 24317975
TI  - Tandem repeat-containing MITEs in the clam Donax trunculus.
AB  - Two distinct classes of repetitive sequences, interspersed mobile elements and
      satellite DNAs, shape eukaryotic genomes and drive their evolution. Short arrays
      of tandem repeats can also be present within nonautonomous miniature inverted
      repeat transposable elements (MITEs). In the clam Donax trunculus, we
      characterized a composite, high copy number MITE, named DTC84. It is composed of
      a central region built of up to five core repeats linked to a microsatellite
      segment at one array end and flanked by sequences holding short inverted repeats.
      The modular composition and the conserved putative target site duplication
      sequence AA at the element termini are equivalent to the composition of several
      elements found in the cupped oyster Crassostrea virginica and in some insects. A
      unique feature of D. trunculus element is ordered array of core repeat variants,
      distinctive by diagnostic changes. Position of variants in the array is fixed,
      regardless of alterations in the core repeat copy number. Each repeat harbors a
      palindrome near the junction with the following unit, being a potential hotspot
      responsible for array length variations. As a consequence, variations in number
      of tandem repeats and variations in flanking sequences make every sequenced
      element unique. Core repeats may be thus considered as individual units within
      the MITE, with flanking sequences representing a "cassette" for internal repeats.
      Our results demonstrate that onset and spread of tandem repeats can be more
      intimately linked to processes of transposition than previously thought and
      suggest that genomes are shaped by interplays within a complex network of
      repetitive sequences.

PMID- 24317977
TI  - A recollection of the development of the Kok-Joliot model for photosynthetic
      oxygen evolution.
AB  - Twenty-five years of period-four O2-flash yield oscillation are celebrated with a
      personal recollection of the development of the Kok-Joliot model for
      photosynthetic oxygen evolution. 

PMID- 24317978
TI  - Water cleavage by solar radiation-an inspiring challenge of photosynthesis
      research.
AB  - Solar energy exploitation by photosynthetic water cleavage is of central
      relevance for the development and sustenance of all higher forms of living matter
      in the biosphere. The key steps of this process take place within an integral
      protein complex referred to as Photosystem II (PS II) which is anisotropically
      incorporated into the thylakoid membrane. This minireview concentrates on
      mechanistic questions related to i) the generation of strongly oxidizing
      equivalents (holes) at a special chlorophyll a complex (designated as P680) and
      ii) the cooperative reaction of four holes with two water molecules at a
      manganese containing unit WOC (water oxidizing complex) resulting in the release
      of molecular oxygen and four protons. The classical work of Pierre Joliot and
      Bessel Kok and their coworkers revealed that water oxidation occurs via a
      sequence of univalent oxidation steps including intermediary redox states Si (i =
      number of accumulated holes within the WOC). Based on our current stage of
      knowledge, an attempt is made a) to identify the nature of the redox states Si,
      b) to describe the structural arrangement of the (four) manganese centers and
      their presumed coordination and ligation within the protein matrix, and c) to
      propose a mechanism of photosynthetic water oxidation with special emphasis on
      the key step, i.e. oxygen-oxygen bond formation. It is assumed that there exists
      a dynamic equilibrium in S3 with one state attaining the nuclear geometry and
      electronic configuration of a complexed peroxide. This state is postulated to
      undergo direct oxidation to complexed dioxygen by univalent electron abstraction
      with YZ (ox) and simultaneous internal ligand to metal charge transfer.Key
      questions on the mechanism will be raised. The still fragmentary answers to these
      questions not only reflect our limited knowledge but also illustrate the
      challenges for future research. 

PMID- 24317979
TI  - Photosynthetic water oxidation: The protein framework.
AB  - Approximately 20 protein subunits are associated with the PS II complex, not
      counting subunits of peripheral light-harvesting antenna complexes. However, it
      is not yet established which proteins specifically are involved in the water
      oxidation process. Much evidence supports the concept that the D1/D2 reaction
      center heterodimer not only plays a central role in the primary photochemistry of
      Photosystem II, but also is involved in electron donation to P680 and in ligation
      of the manganese cluster. This evidence includes (a) the primary donor to P680
      has been shown to be a redox-active tyrosyl residue (Tyr161) in the D1 protein,
      and (b) site-directed mutagenesis and computer-assisted modeling of the reaction
      center heterodimer have suggested several sites with a possible function in
      manganese ligation. These include Asp170, Gln165 and Gln189 of the D1 protein and
      Glu69 of the D2 protein as well as the C-terminal portion of the mature D1
      protein. Also, hydrophilic loops of the chlorophyll-binding protein CP43 that are
      exposed at the inner thylakoid surface could be essential for the water-splitting
      process.In photosynthetic eukaryotes, three lumenal extrinsic proteins, PS II-O
      (33 kDa), PS II-P (23 kDa) and PS II-Q (16 kDa), influence the properties of the
      manganese cluster without being involved in the actual catalysis of water
      oxidation. The extrinsic proteins together may have multiple binding sites to the
      integral portion of PS II, which could be provided by the D1/D2 heterodimer and
      CP47. A major role for the PS II-O protein is to stabilize the manganese cluster.
      Most experimental evidence favors a connection of the PS II-P protein with
      binding of the Cl(-) and Ca(2+) ions required for the water oxidation, while the
      PS II-Q protein seems to be associated only with the Cl(-) requirement. The two
      latter proteins are not present in PS II of prokaryotic organisms, where their
      functions may be replaced by a 10-12 kDa subunit and a newly discovered low
      potential cytochrome c-550. 

PMID- 24317980
TI  - Perspectives on the structure of the photosynthetic oxygen evolving manganese
      complex and its relation to the Kok cycle.
AB  - This review describes the progress in our understanding of the structure of the
      Mn complex in Photosystem II over the last two decades. Emphasis is on the
      research from our laboratory, especially the results from X-ray absorption
      spectroscopy, low temperature electron paramagnetic resonance and electron spin
      echo envelope modulation studies. The importance of the interplay between
      electron paramagnetic resonance studies and X-ray absorption studies, which has
      led to a description of the oxidation states of manganese as the enzyme cycles
      through the Kok cycle, is described. Finally, the path, by which our group has
      utilized these two important methods to arrive at a working structural model for
      the manganese complex that catalyzes the oxidation of water to dioxygen in higher
      plants and cyanobacteria, is explained. 

PMID- 24317981
TI  - Proton release during the redox cycle of the water oxidase.
AB  - Old and very recent experiments on the extent and the rate of proton release
      during the four reaction steps of photosynthetic water oxidation are reviewed.
      Proton release is discussed in terms of three main sources, namely the chemical
      production upon electron abstraction from water, protolytic reactions of Mn
      ligands (e.g. oxo-bridges), and electrostatic response of neighboring amino
      acids. The extent of proton release differs between the four oxidation steps and
      greatly varies as a function of pH both, but differently, in thylakoids and PS II
      membranes. Contrastingly, it is about constant in PS II-core particles. In any
      preparation, and on most if not all reaction steps, a large portion of proton
      transfer can occur very rapidly (<20 MUs) and before the oxidation of the Mn
      cluster by Yz (+) is completed. By these electrostatically driven reactions the
      catalytic center accumulates bases. An additional slow phase is observed during
      the oxygen evolving step, S3=>S4->S0. Depending on pH, this phase consists of a
      release or an uptake of protons which accounts for the balance between the number
      of preformed bases and the four chemically produced protons. These data are
      compatible with the hypothesis of concerted electron/proton-transfer to overcome
      the kinetic and energetic constraints of water oxidation. 

PMID- 24317982
TI  - Kok's oxygen clock: What makes it tick? The structure of P680 and consequences of
      its oxidizing power.
AB  - New insights in the structure of P680, the primary electron donor in Photosystem
      II, are summarized and the implications of its oxidizing power for energy
      transfer and singlet oxygen production are discussed. 

PMID- 24317983
TI  - The effect of protonation on [Mn(IV)(MU2-O)] 2 complexes.
AB  - The series of complexes [Mn(IV)(X-SALPN)(MU2-O)]2, 1: X=5-OCH3; 2: X=H; 3: X=5
      Cl; 4: X=3,5-diCl; 5: X=5-NO2, contain [Mn2O2](4+) cores with Mn-Mn separations
      of 2.7 A. These molecules can be protonated to form [Mn(IV)(X-SALPN)(MU2-O,OH)]2
      (+) in which a bridging oxide is protonated. The pKa values for the series of
      [Mn(IV)(X-SALPN)(MU2-O,OH)]2 (+) track linearly versus the shift in redox
      potential with a slope of 84 mV/pKa. This observation suggests that the
      [Mn2O2](4+) core can be considered as a unit in which the free energy of
      protonation is directly related to the ability to reduce the Mn(IV) ion. The
      marked sensitivity of the reduction potential to the presence of protons presents
      a mechanism in which an enzyme can control the oxidizing capacity of an oxo
      manganese cluster by the degree and timing of oxo bridge protonation. 

PMID- 24317984
TI  - High misses after odd flashes in oxygen evolution in thoroughly dark-adapted
      thylakoids from pea and Chenopodium album.
AB  - In Photosystem II (PS II), water is oxidized to molecular oxygen and
      plastoquinone is reduced to plastoquinol. The oxidation of water requires the
      accumulation of four oxidizing equivalents, through the so-called S-states of the
      oxygen evolving complex; the production of plastoquinol requires the accumulation
      of two reducing equivalents on a bound plastoquinone, QB. It has been generally
      believed that during the flash-induced transition of each of the S-states (Sn ->
      Sn+1, where n=0, 1, 2 and 3), a certain small but equal fraction of the PS II
      reaction centers are unable to function and, thus, 'miss' being turned over. We
      used thoroughly dark-adapted thylakoids from peas (Pisum sativum) and Chenopodium
      album (susceptible and resistant to atrazine) starting with 100% of the oxygen
      evolving complex in the S1 state. Thylakoids were illuminated with saturating
      flashes, providing a double hit parameter of about 0.07. Our experimental data on
      flashnumber dependent oscillations in the amount of oxygen per flash fit very
      well with a binary pattern of misses: 0, 0.2, 0, 0.4 during S0 -> S1, S1 -> S2,
      S2 -> S3 and S3 -> S0 transitions. Addition of 2 mM ferricyanide appears to shift
      this pattern by one flash. These results are consistent with the 'bicycle' model
      recently proposed by V. P. Shinkarev and C. A. Wraight (Oxygen evolution in
      photosynthesis: From unicycle to bicycle, 1993, Proc Natl Acad Sci USA 90: 1834
      1838), where misses are due to the presence of P(+) or QA (-) among the various
      equilibrium states of PS II centers. 

PMID- 24317985
TI  - Kinetic factors in the bicycle model of oxygen evolution by Photosystem II.
AB  - Flash-induced oxygen evolution and many related processes in thylakoids of
      oxygenic organisms are modulated with period four by the S-state transitions
      associated with the oxygen evolving system of Photosystem II (PS II). To analyze
      these phenomena, we have interpreted the S-state model on the basis of the charge
      accumulating activities on both sides of PS II-4 charges on the donor side and 2
      charges on the acceptor side. This results in the recognition of two parallel
      reaction center cycles V and W of PS II function (V.P. Shinkarev and C.A. Wraight
      (1993) Proc Natl Acad Sci USA 90: 1834-1838). The description of damping of the
      period four oscillations is here extended to include kinetic sources of misses in
      both cycles. Such misses arise in reaction centers (RCs) in which back reaction
      between P(+) and QA (-) occurs before the electron transfer equilibria on the
      donor and acceptor sides of the RC are reached. These are in addition to misses
      which are determined by reaction centers (RCs) that are inactive at the time of
      the flash due to the presence of either P(+) or QA (-) according to the electron
      transfer equilibria on the donor and acceptor sides of the RC. Using known or
      estimated values of the equilibrium and rate constants for donor and acceptor
      side reactions of the RC, this provides a natural and quantitatively reasonable
      description of the flash number dependence of oxygen evolution and other period
      four modulated processes of PS II. The estimated miss factors are different for
      both cycles V and W and are dependent on flash number and pH. Estimates based on
      existing data show that miss factors of the first type (kinetic) are dominant at
      low pH, while those of the second type (equilibrium) are dominant at high pH. 

PMID- 24317986
TI  - Absorbance difference spectra of the S-state transitions in Photosystem II core
      particles.
AB  - Redox changes of the oxygen evolving complex in PS II core particles were
      investigated by absorbance difference spectroscopy in the UV-region. The
      oscillation of the absorbance changes induced by a series of saturating flashes
      could not be explained by the minimal Kok model (Kok et al. 1970) consisting of a
      4-step redox cycle, S0 -> S1 -> S2 -> S3 -> S0, although the values of most of
      the relevant parameters had been determined experimentally. Additional
      assumptions which allow a consistent fit of all data are a slow equilibration of
      the S3 state with an inactive state, perhaps related to Ca(2+)-release, and a low
      quantum efficiency for the first turnover after dark-adaptation. Difference
      spectra of the successive S-state transitions were determined. At wavelengths
      above 370 nm, they were very different due to the different contribution of a Chl
      bandshift in each spectrum. At shorter wavelengths, the S1 -> S2 transition
      showed a difference spectrum similar to that reported by Dekker et al. 1984b and
      attributed to an Mn(III) to Mn(IV) oxidation. The spectrum of absorbance changes
      associated with the S2 -> S3 transition was similar to that reported by Lavergne
      1991 for PS II membranes. The S0 -> S1 transition was associated with a smaller
      but still substantial absorbance increase in the UV. Differences with the spectra
      reported by Lavergne 1991 are attributed to electrostatic effects on electron
      transfer at the acceptor side associated with the S-state dependence of proton
      release in PS II membranes. 

PMID- 24317987
TI  - Manganese K-edge X-ray absorption spectra of the cyclic S-states in the
      photosynthetic oxygen-evolving system.
AB  - A set of Mn K-edge XANES spectra due to the redox states S0-S3 of the OEC were
      determined by constructing a highly-sensitive X-ray detection system for use with
      physiologically native PS II membranes capable of cycling under a series of
      saturating laser-flashes. The spectra showed almost parallel upshifts with
      relatively high K-edge half-height energies given by 6550.9+/-0.2 eV, 6551.7+/
      0.2 eV, 6552.5+/-0.2 eV and 6553.6+/-0.2 eV for the S0, S1, S2 and S3 states,
      respectively. The successive difference spectra between S0 and S1, S1 and S2, and
      S2 and S3 states were found to exhibit a similar peak around 6552-6553 eV,
      indicating that one Mn(III) ion or its direct ligand is univalently oxidized upon
      each individual S-state transition from S0 to S3. The present data, together with
      other observations of EPR and pre-edge XANES spectroscopy, suggest that the
      oxidation state of the Mn cluster undergoes a periodic change; S0:
      Mn(III,III,III,IV) -> S1: Mn(III,IV,III,IV) -> S2: Mn(III,IV,IV,IV) -> S3:
      Mn(IV,IV,IV,IV) or Mn(III,IV,IV,IV).L(+) with L being a direct ligand of a
      Mn(III) ion. 

PMID- 24317988
TI  - Spectroscopic studies of the manganese complex of Photosystem II.
AB  - Our recent EPR and EXAFS experiments investigating the structure of the oxygen
      evolving complex of PS II are discussed. PS II treatments which affect the
      cofactors calcium and chloride have been used to poise samples in modified forms
      of the S-states, S1, S2 and S3. X-ray absorption studies indicate a similar
      overall structure for the manganese complex between treated and native samples
      although the influence of the treatments and cofactors is observed. Manganese
      oxidation (or oxidation of a ligand to the manganese cluster) is indicated to
      occur on each of the transitions S1 ->S2 and S2 ->S3 in these modified samples.
      The cluster appears to contain at least two inequivalent Mn-Mn pairs. In the
      native samples the Mn-Mn distance is 2.7 A, but in samples where the calcium site
      is affected, one of the pairs has a 3.0 A Mn-Mn distance. The intensity of the
      3.3/3.6 A interaction is reduced on sodium chloride treatment (calcium depletion)
      perhaps indicating calcium binding close to the manganese cluster. From EPR data
      we also propose that treatments which affect calcium and chloride binding cause a
      modification of the native S2 state, slow the reduction of Yz (*) and allow an S3
      EPR signal to be observed following illumination. The origin of the S3 EPR
      signal, a modified S3 or S2 X(*) where X(*) is an organic radical of unknown
      charge, is discussed in relation to the results from the EXAFS studies. 

PMID- 24317989
TI  - NMR paramagnetic relaxation enhancements due to manganese in the S0 and S 2
      states of Photosystem II-enriched membrane fragments and in the detergent
      solubilized Photosystem II complex.
AB  - The NMR paramagnetic relaxation enhancement (NMR-PRE) produced in the solvent
      proton resonance by manganese in the S0 and S2 states of the oxygen evolving
      center (OEC) has been recorded for three Photosystem II (PS II)-enriched
      preparations: (1) PS II-enriched thylakoid membrane fragments (TMF-2 particles);
      (2) salt-washed (2M NaCl) TMF-2 particles; and (3) the octylglucopyranoside (OGP)
      solubilized PS II complex. The second and third preparations, but not the first,
      are depleted of the peripheral 17 and 23 kD polypeptides associated with the OEC.
      It has been proposed that depletion of these polypeptides increases the exposure
      of OEC manganese to the aqueous phase. The NMR-PRE response measures the quantity
      (T1m+taum)(-1), where T1m is the spin relaxation time and taum is the mean
      residence time with respect to chemical exchange reactions of solvent protons in
      the manganese coordination sphere, and, thus, the NMR-PRE provides a direct
      measure of the solvent proton chemical exchange rate constant taum (-1). This
      study tested whether the 17 and 23 kD polypeptides shield the OEC from the
      solvent phase and whether their depletion enhances the S2 and S0 NMR-PRE signals
      by removing a kinetic barrier to the solvent proton chemical exchange reaction.
      The amplitude of the S2 NMR-PRE signal, measured in its chemical exchange-limited
      regime (taum>T1m), is slightly decreased, rather than increased, in preparations
      (2) and (3) relative to (1), indicating that removal of the 17 and 23 kD
      polypeptides slightly slows, rather than accelerates, the rate-limiting steps of
      the solvent proton chemical exchange reactions. In addition, the lifetime of the
      S2 state was shortened several-fold in the solubilized PS II complex and in salt
      washed TMF-2 membranes relative to untreated TMF-2 control samples. The S0 NMR
      PRE signal, which is present in TMF-2 suspensions, was not detected in
      suspensions of the solubilized PS II complex, even though these samples contained
      high concentrations of active manganese centers (approximately double those of
      the TMF-2 control) and exhibited an S2 NMR-PRE signal of comparable amplitude to
      that of the TMF-2 preparation. These results suggest that the 17 and 23 kD
      extrinsic polypeptides do not shield the NMR-visible water binding site in the
      OEC from the aqueous phase, although their removal substantially alters the
      proton relaxation efficiency by shortening T1m. 

PMID- 24317990
TI  - A mass spectrometric analysis of the water-splitting reaction.
AB  - Earlier mass spectrometric measurements, in which oxygen evolution was measured
      following short saturating light flashes, indicated that with a time resolution
      of about 30 s no form of bound water and/or an oxidation product exists up to the
      redox state S3 of the oxygen evolving center (R. Radmer and O. Ollinger, 1986,
      FEBS Lett 195: 285-289; K.P. Bader, P. Thibault and G.H. Schmid, 1987, Biochim
      Biophys Acta 893: 564-571). In the present study, isotope exchange experiments
      with H2 (18)O were performed under different experimental conditions. We found:
      a) the isotope exchange pattern is virtually the same at both pH 6.0 and 7.8,
      although marked structural changes of the PS II donor side are inferred to take
      place within this pH-range (Renger G., Messinger J. and Wacker U., 1992, Research
      in Photosynthesis, II: 329-332); b) injection of H2 (18)O at about 0 degrees C
      gives rise to mass ratios of the evolved oxygen which markedly deviate from the
      theoretically expected values of complete isotope scrambling; and c) rapid
      injection of H2 (18)O into samples with high population of S1 and S2 and
      subsequent illumination with three and two flashes, respectively, spaced by a
      dark time of only 1.5 ms lead to similar (18)O-labeling of the evolved oxygen.
      Based on the published data on the interaction with redox active amines, possible
      pathways of substrate exchange in the water oxidase are discussed. 

PMID- 24317991
TI  - Functional size of Photosystem II determined by radiation inactivation.
AB  - The functional size of Photosystem II (PS II) was investigated by radiation
      inactivation. The technique provides an estimate of the functional mass required
      for a specific reaction and depends on irradiating samples with high energy gamma
      rays and assaying the remaining activity. The analysis is based on target theory
      that has been modified to take into account the temperature dependence of
      radiation inactivation of proteins. Using PS II enriched membranes isolated from
      spinach we determined the functional size of primary charge separation coupled to
      water oxidation and quinone reduction at the QB site: H2O -> (Mn)4 -> Yz -> P680 
      > Pheophytin -> Q -> phenyl-p-benzoquinone. Radiation inactivation analysis
      indicates a functional mass of 88 +/- 12 kDa for electron transfer from water to
      phenyl-p-benzoquinone. It is likely that the reaction center heterodimer
      polypeptides, D1 and D2, contribute approximately 70 kDa to the functional mass,
      in which case polypeptides adding up to approximately 20 kDa remain to be
      identified. Likely candidates are the alpha and beta subunits of cytochrome b
      559and the 4.5 kDa psbI gene product. 

PMID- 24317992
TI  - Characterization of the psbK locus of Synechocystis sp. PCC 6803 in terms of
      Photosystem II function.
AB  - The psbK gene encodes a small protein of Photosystem II. The gene has previously
      been cloned and sequenced in Synechocystis sp. PCC 6803. Our new results,
      presented here, confirm the conclusions of Ikeuchi et al. Based on Northern
      hybridization and primer extension analyses, we show that psbK is transcribed as
      a monocistronic message in this cyanobacterium. Analysis of DNA sequence
      immediately upstream of the transcription start site revealed an E. coli-like-10
      consensus sequence. A deletion mutant was constructed where the psbK gene was
      replaced by a kanamycin resistant cartridge. In situ complementation experiments,
      as well as Southern and Northern hybridization analyses, confirmed that the
      mutant strain contains a lesion in psbK. The psbK-less mutant could grow
      photoautotrophically as well as photoheterotrophically both in liquid culture and
      on agar plates. The rate of growth was slightly less compared with the wild-type
      as clearly observed by in situ complementation experiments. Although the mutant
      showed correspondingly lower rates of electron transport, thermoluminescence,
      oxygen flash yield and chlorophyll a fluorescence measurements did not detect any
      significant modification of the reactions of PS II. Moreover, the mutant was no
      more susceptible to excess light than the wild-type. It is, therefore, concluded
      that the product of the psbK gene is not crucial for PS II activity and possibly
      plays some other role in the metabolism of Synechocystis. 

PMID- 24317993
TI  - Analytical procedures for the quantification of isotopic amino acid incorporation
      into photosynthetic proteins of Synechocystis PCC 6803.
AB  - The mechanism of oxygen evolution has been an enigma for nearly two centuries.
      Pioneering work by Bessel Kok, Pierre Joliot, and many others during the last
      quarter century has provided valuable insight into this most unique and important
      chemical reaction. The late 1970s and early 1980s saw the introduction of
      biochemical techniques for the purification of photosynthetic complexes that
      have, in turn, stimulated the biophysical chemists and spectroscopists to apply
      high resolution techniques in order to resolve the structure/function
      relationships in these protein complexes. Valuable information about events at
      the atomic level can be gained through isotopic substitution of particular amino
      acids thought to be important in the catalytic process. The ability to generate
      functional auxotrophs in the photosynthetic cyanobacterium Synechocystis 6803 has
      been used successfully to identify the redox active components Z and D as
      tyrosine residues in the reaction center of Photosystem II. In this report, we
      present results of the application of specific isotopic labeling for high
      resolution spectroscopy of purified PS II particles. We have developed analytical
      procedures for monitoring the incorporation of both (2)H and (17)O labeled amino
      acids by gas chromatography-mass spectroscopic analysis. We also show that the
      growth curve of cells subjected to obligate auxotrophy displays two distinct
      stationary phases; one that corresponds to depletion of exogenous amino acids,
      and a second that corresponds to the normal cell density at stationary phase.
      Cells harvested at the second stationary phase show little or no retention of the
      labeled amino acid. 

PMID- 24317994
TI  - The primary structure of D1 near the QB pocket influences oxygen evolution.
AB  - Photosystem II (PS II) is the site of oxygen evolution. Activation of dark
      adapted samples by a train of saturating flashes produces oxygen with a yield per
      flash which oscillates with a periodicity of four. Damping of the oxygen
      oscillations is accounted for by misses and double hits. The mechanisms hidden
      behind these parameters are not yet fully understood. The components which
      participate in charge transfer and storage in PS II are believed to be anchored
      to the heterodimer formed by the D1 and D2 proteins. The secondary plastoquinone
      acceptor QB binds on D1 in a loop connecting the fourth and fifth helices (the QB
      pocket). Several D1 mutants, mutated in the QB binding region, have been studied
      over the past ten years.In the present report, our results on nine D1 mutants of
      Synechocystis PCC 6714 and 6803 are analyzed. When oxygen evolution is modified,
      it can be due to a change in the electron transfer kinetics at the level of the
      acceptor side of PS II and also in some specific mutants to a long ranging effect
      on the donor side of PS II. The different properties of the mutants enable us to
      propose a classification in three categories. Our results can fit in a model in
      which misses are substantially determined by the fraction of centers which have
      QA (-) before each flash due to the reversibility of the electron transfer
      reactions. This idea is not new but was more thoroughly studied in a recent paper
      by Shinkarev and Wraight (1993). However, we will show in the discussion that
      some doubts remain as to the true origin of misses and double hits. 

PMID- 24317995
TI  - Thermoluminescence properties of the S2-state in chloride-depleted water
      oxidizing complexes after reconstituting treatments with various monovalent
      anions.
AB  - Under conditions that assured rebinding of the extrinsic 17 and 23 kDa
      polypeptides, Cl(-)-depleted Photosystem II membranes isolated from spinach
      chloroplasts were subjected to reconstituting treatments in media containing NaF,
      NaCl, NaBr, NaI or NaNO3, or they were kept in a medium without any added salt
      other than the buffer. After removing most of the unbound reconstituting anions
      by washing, the O2-evolution activities and thermoluminescence properties of the
      membranes were compared. While the temperature of maximal thermoluminescence
      emission was lowest for membranes treated with Cl(-), no uniform correlation was
      evident between the temperature profile of the thermoluminescence emission and
      the apparent activating effectiveness of the anions in the membranes' water
      oxidizing machinery. However, the differences between the thermoluminescence
      features did conform to a trend according to which the emission temperatures were
      upshifted as the size of the activating anion increased, and its hydration energy
      decreased, i.e. Cl(-)<Br(-)<NO3 (-)<I(-). The inactive F(-) anions were not well
      retained by the membranes. To explain the experimental data it is suggested that
      the structural environment of the charge accumulating Mn-center is influenced by
      the ionic conditions encountered by the Photosystem II membranes after Cl(-)
      removal, further enforced by the binding of compatible anions, and then
      stabilized by the 17 and 23 kDa extrinsic polypeptides. If, as some concepts
      imply, the anion binding sites are located at or near the functional Mn, only
      very exceptional characteristics of the water-oxidizing mechanism may account for
      the observation that the potentially electron-donating I(-) anion can serve as
      activator and that it stabilizes rather than destabilizes the S2-state. 

PMID- 24317996
TI  - Studies of the slowly exchanging chloride in Photosystem II of higher plants.
AB  - (36)Cl(-) was used to study the slow exchange of chloride at a binding site
      associated with Photosystem II (PS II). When PS II membranes were labeled with
      different concentrations of (36)Cl(-), saturation of binding at about I
      chloride/PS II was observed. The rate of binding showed a clear dependence on the
      concentration of chloride approaching a limiting value of about 3.10(-4) s(-1) at
      high concentrations, similar to the rate of release of chloride from labeled
      membranes. These rates were close to that found earlier for the release of
      chloride from PS II membranes isolated from spinach grown on (36)Cl(-), which
      suggests that we are observing the same site for chloride binding. The similarity
      between the limiting rate of binding and the rate of release of chloride suggests
      that the exchange of chloride with the surrounding medium is controlled by an
      intramolecular process. The binding of chloride showed a pH-dependence with an
      apparent pKa of 7.5 and was very sensitive to the presence of the extrinsic
      polypeptides at the PS II donor side. The binding of chloride was competitively
      inhibited by a few other anions, notably Br(-) and NO3 (-). The slowly exchanging
      Cl(-) did not show any significant correlation with oxygen evolution rate or
      yield of EPR signals from the S2 state. Our studies indicate that removal of the
      slowly exchanging chloride lowers the stability of PS II as indicated by the loss
      of oxygen evolution activity and S2 state EPR signals. 

PMID- 24317997
TI  - Photoproduction of hydrogen peroxide in Photosystem II membrane fragments: A
      comparison of four signals.
AB  - The present study describes the formation of different forms of peroxide in
      Photosystem II (PS II) by using a chemiluminescence detection technique. Four
      chemiluminescence signals (A, B, C and D) of the luminolperoxidase (Lu-Per)
      system, which detects peroxide, are found in illuminated O2-evolving Photosystem
      II (PS II) membrane fragments isolated from spinach. Signal A ('free peroxide')
      peaking around 0.2-0.3 s after mixing PS II membrane fragments with Lu-Per is
      eliminated by catalase or removal of oxygen from the suspension and ascribed to
      O2 interaction with reduced PS II electron acceptors. In contrast, signal B
      peaking around 1.5 min remains largely unaffected under anaerobic conditions, as
      well as in the presence of catalase (20 MUg/ml). Under flash illumination the
      extent of this signal exhibits a weak period four oscillation (maximum at third
      and 7th flash). Its yield increases up to the third flash, but is close to zero
      in the fourth flash. An analogous behaviour is observed in flashes 5 to 8. Signal
      B is ascribed to Lu-Per interaction with the water-oxidizing system being in S2
      and/or S3-state. Signal C ('bound peroxide') detected as free peroxide after acid
      decomposition of illuminated PS II particles is observed on the 1 st flash and
      oscillates with period 2 with superposition of period 4. It is evidently related
      to peroxide either released from S2 or formed at S2 upon acid shock treatment.
      Signal D ('slowly released peroxide') peaking around 2-3 s after mixing is
      observed in samples after various treatments (LCC-incubation, washing with 1 M
      NaCl at pH 8 or with 1 M CaCl2, Cl(-)-depletion) that lead to at least partial
      removal of the extrinsic proteins of 18, 24 and 33 kDa without Mn extraction. The
      average amplitude of this signal corresponds with a yield of about 0.2 H2O2
      molecules per RC and flash. In a flash train, the extent of signal D exhibits an
      oscillation pattern with a minimum at the 3rd flash. We assume that these
      treatments increase the release of 'bound' peroxide (upon injection into the Lu
      Per assay) either formed in the normal oxidative pathway of the water oxidase in
      the S2 or the S3-state or give rise to peroxide formation due to higher
      accessibility of the Mn-cluster to water molecules. 

PMID- 24317998
TI  - Increases in peroxide formation by the Photosystem II oxygen evolving reactions
      upon removal of the extrinsic 16, 22 and 33 kDa proteins are reversed by CaCl2
      addition.
AB  - This communication introduces a new spectrophotometric assay for the detection of
      peroxide generated by Photosystem II (PS II) under steady state illumination in
      the presence of an electron acceptor. The assay is based on the formation of an
      indamine dye in a horseradish peroxidase coupled reaction between 3
      (dimethylamino)benzoic acid and 3-methyl-2-benzothiazolinone hydrazone. Using
      this assay, we found that as the O2 evolution activity of PS II-enriched membrane
      fragments is decreased by treatments which cause the dissociation of the 33
      and/or 23 and 16 kDa extrinsic proteins (i.e., CaCl2-washing, NaCl-washing,
      lauroylcholine-treatment and ethylene glycol-treatment), light-induced peroxide
      formation increases. Both the losses of O2 evolution and increases in peroxide
      formation seen under these conditions are reversed by CaCl2 addition, indicating
      that the two activities originate from the water-splitting site. However, the
      increased rates of peroxide formation do not quantitatively match the losses in
      O2 evolution activity. We suggest that a rapid consumption of the peroxide takes
      place via a catalase/peroxidase activity at the water-splitting site which
      competes with both the O2 evolution and peroxide formation reactions. The
      observed peroxide formation is interpreted as arising from enhanced water
      accessibility to the catalytic site upon perturbation of the extrinsic proteins
      which then leads to alternate water oxidation side reactions. 

PMID- 24317999
TI  - Slow oxygen release on the first two flashes in chemically stressed Photosystem
      II membrane fragments results from hydrogen peroxide oxidation.
AB  - Flash-induced amperometric signals were measured with a Joliot-type O2 rate
      electrode in spinach Photosystem II (PS II) membrane fragments exposed to very
      low concentrations of added hydroxylamine or hydrogen peroxide. In both cases
      'anomalous O2 signals' were observed on the first two flashes, and oscillating
      four-flash patterns were observed on subsequent flashes. The anomalous signals
      were eliminated in the presence of catalase but not EDTA. The rise times of the
      O2-release kinetics associated with the anomalous signals were slow (ca. 20 ms
      with NH2OH and ca. 120 ms with H2O2) compared to the kinetics of O2 release on
      subsequent flashes and in control membranes (3-6 ms). It is proposed that when
      the intact PS II O2-evolving complex is perturbed with small concentrations of
      added reductant, H2O2 can gain access and bind to the complex. Bound H2O2 can
      then reduce lower S states in some centers leading to anomalous O2 signals on the
      first two flashes. A model is presented to explain both types of anomalous O2
      production. Oxygen observed on the third and subsequent flashes is due to the
      normal photosynthetic O2-evolution process arising from the S3-state. Anomalous
      O2 production could be a protective mechanism in PS II centers subjected to
      stress conditions. 

PMID- 24318000
TI  - Inhibition of the catalase reaction of Photosystem II by anions.
AB  - A new binding site for anions which inhibit the water oxidizing complex (WOC) of
      Photosystem II in spinach has been identified. Anions which bind to this site
      inhibit the flash-induced S2/S0 catalase reaction (2H2O2->2H2O+O2) of the WOC by
      displacing hydrogen peroxide. Using a mass spectrometer and gas permeable
      membrane to detect the (32)O2 product, the yield and lifetime of the active state
      of the flash-induced catalase (to be referred to simply as 'flash-catalase')
      reaction were measured after forming the S2 or S0-states by a short flash. The
      increase in flash-catalase activity with H2O2 concentration exhibits a Km=10-20
      mM, and originates from an increase in the lifetime by 20-fold of the active
      state. The increased lifetime in the presence of peroxide is ascribed to
      formation of the long-lived S0-state at the expense of the unstable S2-state. The
      anion inhibition site differs from the chloride site involved in stimulating the
      photolytic water oxidation reaction (2H2O->O2+4e(-)+4H(+)). Whereas water
      oxidation requires Cl(-) and is inhibited with increasing effectiveness by F(
      )?CN(-)?N3 (-), the flash-catalase reaction is weakly inhibited by Cl(-), and
      with increasing effectiveness by F(-)?CN(-), N3 (-). Unlike water oxidation,
      chloride is unable to suppress or reverse inhibition of the flash-catalase
      reaction caused by these anions. The inhibitor effectiveness correlates with the
      pKa of the conjugate acid, suggesting that the protonated species may be the
      active inhibitor. The reduced activity arises from a shortening of the lifetime
      of the flash-induced catalase active state by 3-10 fold owing to stronger anion
      binding in the flash-induced states, S2 and S0, than in the dark S-states, S1 and
      S-1. To account for the paradoxical result that higher anion concentrations are
      required to inhibit at lower H2O2 concentrations, where S2 forms initially after
      the flash, than at higher H2O2 concentrations, where S0 forms initially after the
      flash, stronger anion binding to the S0-state than to the S2-state is proposed. A
      kinetic model is given which accounts for these equilibria with anions and H2O2.
      The rate constant for the formation/release of O2 by reduction of S2 in the WOC
      is <0.4 s(-1). 

PMID- 24318001
TI  - Chemical oxidation and reduction of the O2-evolution center in Photosystem II.
AB  - Treatment of Photosystem II (PS II) with low concentrations of hydroxylamine is
      known to cause a two-flash delay in the O2-evolution pattern, and in the
      formation of the S2-state multiline EPR signal, due to the two-electron reduction
      of the S1-state by hydroxylamine to form the S-1-state. Past work has shown that
      these delays are not reversed by washing out the hydroxylamine nor by adding DCBQ
      or ferricyanide to oxidize the residual hydroxylamine, but are reversed by
      illumination with two saturating flashes followed by a 30-min dark incubation. We
      have examined the effects of treatments aimed at restoring the normal flash
      induced O2-evolution pattern and S2-state multiline EPR signal after treatment of
      PS II with 40 MUM hydroxylamine. In agreement with past work, we find that the
      two-flash delay in O2 evolution is not reversed when the hydroxylamine is removed
      by three cycles of centrifugation and resuspension in hydroxylamine-free buffer
      nor by adding ferricyanide or DCBQ to oxidize the unreacted hydroxylamine.
      However, the normal flash-induced O2-evolution pattern is restored by
      illumination with two saturating flashes followed by a 30-min dark incubation
      (after the sample was first treated with 40 MUM hydroxylamine and the unreacted
      hydroxylamine was removed); illumination with one saturating flash followed by a
      30-min dark incubation is only partially effective. These results show that
      ferricyanide and DCBQ are not effective at oxidizing the S-1-state to the S1
      state. In contrast, adding hypochlorite (OCl(-)) after treatment with
      hydroxylamine restored the normal flash-induced O2-evolution pattern and also
      restored the formation of the S2-state multiline EPR signal by illumination at
      200 K. We conclude that hypochlorite is capable of oxidizing the S-1-state to the
      S1-state. This is the first example of a chemical treatment that advances the
      delayed flash-induced O2 evolution pattern. 

PMID- 24318002
TI  - Characterization of inhibitory effects of NH2OH and its N-methyl derivatives on
      the O 2-evolving complex of Photosystem II.
AB  - Inorganic cofactors (Mn, Ca(2+) and Cl(-)) are essential for oxidation of H2O to
      O2 by Photosystem II. The Mn reductants NH2OH and its N-methyl derivatives have
      been employed as probes to further examine the interactions between these species
      and Mn at the active site of H2O oxidation. Results of these studies show that
      the size of a hydroxylamine derivative regulates its ability to inactivate O2
      evolution activity, and that this size-dependent inhibition behavior arises from
      the protein structure of Photosystem II. A set of anions (Cl(-), F(-) and SO4 (2
      )) is able to slow NH2OH and CH3NHOH inactivation of intact Photosystem II
      membranes by exerting a stabilizing influence on the extrinsic 23 and 17 kDa
      polypeptides. In contrast to this non-specific anion effect, only Cl(-) is
      capable of attenuating CH3NHOH and (CH3)2NOH inhibition in salt-washed
      preparations lacking the 23 and 17 kDa polypeptides. However, Cl(-) fails to
      protect against NH2OH inhibition in salt-washed membranes. These results indicate
      that the attack by NH2OH and its N-methyl derivatives on Mn occurs at different
      sites in the O2-evolving complex. The small reductant NH2OH acts at a Cl(-)
      insensitive site whereas the inhibitions by CH3NHOH and (CH3)2NOH involve a site
      that is Cl(-) sensitive. These findings are consistent with earlier studies
      showing that the size of primary amines controls the Cl(-) sensitivity of their
      binding to Mn in the O2-evolving complex. 

PMID- 24318003
TI  - Inactivation of photosynthetic oxygen evolution by UV-B irradiation: A
      thermoluminescence study.
AB  - The influence of UV-B irradiation on photosynthetic oxygen evolution by isolated
      spinach thylakoids has been investigated using thermoluminescence measurements.
      The thermoluminescence bands arising from the S2QB (-) (B band) and S2QA (-) (Q
      band) charge recombination disappeared with increasing UV-B irradiation time. In
      contrast, the C band at 50 degrees C, arising from the recombination of QA (-)
      with an accessory donor of Photosystem II, was transiently enhanced by the UV-B
      irradiation. The efficiency of DCMU to block QA to QB electron transfer decreased
      after irradiation as detected by the incomplete suppression of the B band by
      DCMU. The flash-induced oscillatory pattern of the B band was modified in the UV
      B irradiated samples, indicating a decrease in the number of centers with reduced
      QB. Based on the results of this study, UV-B irradiation is suggested to damage
      both the donor and acceptor sides of Photosystem II. The damage of the water
      oxidizing complex does not affect a specific S-state transition. Instead, charge
      stabilization is enhanced on an accessory donor. The acceptor-side modifications
      decrease the affinity of DCMU binding. This effect is assumed to reflect a
      structural change in the QB/DCMU binding site. The preferential loss of dark
      stable QB (-) may be related to the same structural change or could be caused by
      the specific destruction of reduced quinones by the UV-B light. 

PMID- 24318004
TI  - Cobalt chloride induced stimulation of Photosystem II electron transport in
      Synechocystis sp. PCC 6803 cells.
AB  - Synechocystis sp. PCC 6803 when grown in the presence of sublethal (MUM) levels
      of cobalt chloride shows an enhancement of Photosystem II (PS II) catalyzed Hill
      reaction. This stimulation seems to be induced by cobalt ions as other metal ions
      inhibit para-benzoquinone catalyzed Hill reaction. At saturating white light
      intensity, this enhancement is two times over that of the control cells on unit
      chlorophyll basis. Analysis of the PS II electron transport rate at varying
      intensities of white, blue or yellow light suggests an increased maximal rates
      but no change in the quantum yield or effective antenna size of CoCl2-grown
      cells. There were no structural and functional changes in the phycobilisome as
      judged by the absence of changes in the phycocyanin/allophycocyanin ratio,
      fluorescence emission spectra, second derivative absorption spectra at 77 K and
      SDS-PAGE analysis of isolated phycobilisomes. The 77 K fluorescence emission
      spectra of the cells showed a decrease in the ratio of Photosystem I emission
      (F725) to Photosystem II emission (F685) in CoCl2-grown cells compared to the
      control cells. These observations indicate three possibilities: (1) there is an
      increase in the number of Photosystem II units; (2) a faster turnover of
      Photosystem II centers; or (3) an alteration in energy redistribution between PS
      II and PS I in CoCl2-grown cells which causes stimulation of Photosystem II
      electron transport rate. 

PMID- 24318005
TI  - Differential pharmacokinetics and the brain distribution of morphine and
      ephedrine constitutional isomers in rats after oral administration with Keke
      capsule using rapid-resolution LC-MS/MS.
AB  - Opioid and ephedra alkaloids known as the active ingredients for Keke capsule,
      which is used to treat coughs and bronchial asthma, could have potential adverse
      effects on the central nervous system. Therefore, an efficient, sensitive rapid
      resolution LC-MS/MS method for the simultaneous determination of morphine,
      ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been
      developed. The method was validated in the plasma and brain tissue samples,
      showed good linearity over a wide concentration range (r(2) > 0.99). The intra-
      and interday assay variability was less than 15% for all analytes, and the
      accuracy was between -8.8 and 5.7%. The study provided the pharmacokinetics
      profiles and the brain regional distribution of the three active alkaloids after
      oral administration of Keke capsule. The results also indicated that significant
      difference in pharmacokinetics parameters of the epimers was observed between
      ephedrine and pseudoephedrine. 

PMID- 24318006
TI  - Osmoporation: a simple way to internalize hydrophilic molecules into yeast.
AB  - Internalization of hydrophilic molecules into yeast cytosol is required for
      different applications such as cell transformation or preservation of water
      soluble components by bioencapsulation. However, these molecules are not able to
      cross the plasma membrane and strategies have to be developed. Recent works
      revealed that osmotic perturbations could induce non-lethal transient
      permeabilization of the plasma membrane. In this work, we endeavored to clarify
      the phenomenon of permeabilization during rehydration after a mild hyperosmotic
      perturbation in order to evaluate the possibility of hydrophilic molecule
      internalization in yeast by this treatment. Rehydration step is particularly
      interesting because the large entry of water into the cells could help the
      internalization of molecules. The internalization of a fluorescent molecule
      [fluorescein isothiocyanate Dextran (FITC-Dextran), 20 kDa], added during the
      rehydration after a sublethal hyperosmotic treatment, was studied in
      Saccharomyces cerevisiae yeast cells. The internalization kinetic and the
      localization of the fluorescent molecules were studied by flow cytometry and
      fluorescence confocal microscopy. Our results show that the rehydration leads to
      the rapid internalization of FITC-Dextran due to a transient plasma membrane
      permeabilization. Thus, osmoporation, i.e. plasma membrane poration by
      modifications of osmotic pressure of the extracellular medium, could be a new and
      simple way to deliver molecules of particular interest into yeasts.

PMID- 24318008
TI  - Biotechnological applications of halophilic lipases and thioesterases.
AB  - Lipases and esterases are enzymes which hydrolyze ester bonds between a fatty
      acid moiety and an esterified conjugate, such as a glycerol or phosphate. These
      enzymes have a wide spectrum of use in industrial applications where their high
      activity, broad substrate specificity, and stability under harsh conditions have
      made them integral in biofuel production, textile processing, waste treatment,
      and as detergent additives. To date, these industrial applications have mainly
      leveraged enzymes from mesophilic and thermophilic organisms. However,
      increasingly, attention has turned to halophilic enzymes as catalysts in
      environments where high salt stability is desired. This review provides a brief
      overview of lipases and esterases and examines specific structural motifs and
      evolutionary adaptations of halophilic lipases. Finally, we examine the state of
      research involving these enzymes and provide an in-depth look at an exciting
      algal-based biofuel production system. This system uses a recombinant halophilic
      lipase to increase oil production efficiency by cleaving algal fatty acids from
      the acyl carrier protein, which eliminates feedback inhibition of fatty acid
      synthesis. 

PMID- 24318007
TI  - A quantitative study of eicosapentaenoic acid (EPA) production by Nannochloropsis
      gaditana for aquaculture as a function of dilution rate, temperature and average
      irradiance.
AB  - Different pilot-scale outdoor photobioreactors using medium recycling were
      operated in a greenhouse under different environmental conditions and the growth
      rates (0.1 to 0.5 day(-1)) obtained evaluated in order to compare them with
      traditional systems used in aquaculture. The annualized volumetric growth rate
      for Nannochloropsis gaditana was 0.26 g l(-1) day(-1) (peak 0.4 g l(-1) day(-1))
      at 0.4 day(-1) in a 5-cm wide flat-panel bioreactor (FP-PBR). The biomass
      productivity achieved in this reactor was 10-fold higher than in traditional
      reactors, reaching values of 28 % and 45 % dry weight (d.w.) of lipids and
      proteins, respectively, with a 4.3 % (d.w.) content of eicosapentaenoic acid
      (EPA). A model for predicting EPA productivity from N. gaditana cultures that
      takes into account the existence of photolimitation and photoinhibition of growth
      under outdoor conditions is presented. The effect of temperature and average
      irradiance on EPA content is also studied. The maximum EPA productivity attained
      is 30 mg l(-1) day(-1).

PMID- 24318010
TI  - Induction of a photomixotrophic plant cell culture of Helianthus annuus and
      optimization of culture conditions for improved alpha-tocopherol production.
AB  - Tocopherols, collectively known as vitamin E, are lipophilic antioxidants, which
      are synthesized only by photosynthetic organisms. Due to their enormous potential
      to protect cells from oxidative damage, tocopherols are used, e.g., as
      nutraceuticals and additives in pharmaceuticals. The most biologically active
      form of vitamin E is alpha-tocopherol. Most tocopherols are currently produced
      via chemical synthesis. Nevertheless, this always results in a racemic mixture of
      different and less effective stereoisomers because the natural isomer has the
      highest biological activity. Therefore, tocopherols synthesized in natural
      sources are preferred for medical purposes. The annual sunflower (Helianthus
      annuus L.) is a well-known source for alpha-tocopherol. Within the presented
      work, sunflower callus and suspension cultures were established growing under
      photomixotrophic conditions to enhance alpha-tocopherol yield. The most efficient
      callus induction was achieved with sunflower stems cultivated on solid Murashige
      and Skoog medium supplemented with 30 g l(-1) sucrose, 0.5 mg l(-1) of the auxin
      1-naphthalene acetic acid, and 0.5 mg l(-1) of the cytokinin 6-benzylaminopurine.
      Photomixotrophic sunflower suspension cultures were induced by transferring
      previously established callus into liquid medium. The effects of light intensity,
      sugar concentration, and culture age on growth rate and alpha-tocopherol
      synthesis rate were characterized. A considerable increase (max. 230%) of alpha
      tocopherol production in the cells was obtained within the photomixotrophic cell
      culture compared to a heterotrophic cell culture. These results will be useful
      for improving alpha-tocopherol yields of plant in vitro cultures.

PMID- 24318011
TI  - Structural and functional assessment by hemispheric asymmetry testing of the
      macular region in preperimetric glaucoma.
AB  - PURPOSE: To investigate structural measurements of the macular area in
      preperimetric glaucoma (PG) patients using spectral domain optical coherence
      tomography with two functional measurements [10-2 Humphrey visual field (HFA) and
      10-2 Microperimeter-1 (MP-1)] and by macular symmetry testing. METHODS: Fifteen
      eyes of 15 PG subjects with a retinal nerve fiber layer defect in the inferior
      hemisphere and 15 eyes of 15 normal control subjects were enrolled. Macular
      symmetry testing was performed between the superior and inferior zones by
      comparing zone thickness in each hemisphere. Perimetric sensitivity asymmetry was
      calculated with two functional measurements. Structure-function relationships
      between macular symmetry testing and the mean retinal sensitivity of the
      corresponding hemifield or perimetric sensitivity asymmetry were calculated using
      Spearman's rank correlation and linear regression. RESULTS: Macular zone
      thickness in the abnormal hemispheres was significantly less than that in normal
      hemispheres in PG eyes and the corresponding hemispheres in control eyes (P <
      0.001). Macular symmetry testing was significantly lower in PG eyes compared to
      control eyes (P < 0.001). HFA (10-2) and MP-1 (10-2) correlated significantly (rs
      = 0.81, P < 0.0001). Macular symmetry testing values were significantly
      correlated with perimetric sensitivity and perimetric sensitivity asymmetry with
      two functional measurements (rs = 0.61, P = 0.02; HFA and rs = 0.68, P = 0.006;
      MP-1). CONCLUSIONS: Our results suggest that macular asymmetry analysis can
      reveal the structure-functional relationship in PG eyes.

PMID- 24318012
TI  - Preservation of cranial nerves during removal of the brain for an enhanced
      student experience in neuroanatomy classes.
AB  - Neuroanatomy teaching at the University of Leeds includes the examination of
      isolated brains by students working in small groups. This requires the prosected
      brains to exhibit all 12 pairs of cranial nerves. Traditional methods of removing
      the brain from the skull involve elevating the frontal lobes and cutting each
      cranial nerve as the brain is reflected posteriorly. This can leave a substantial
      length of each nerve attached to the skull base rather than to the removed brain.
      We have found a posterior approach more successful. In this study, five adult
      heads were disarticulated at the level of the thyroid cartilage and placed,
      prone, in a head stand. A wedge of bone from the occipital region was removed
      before the cerebellum and brainstem were elevated to visualize the cranial nerves
      associated with the medulla oblongata, cerebellopontine angle and mesencephalic
      pontine junction prior to cutting them as close to the skull as possible. Five
      brains were successfully removed from the skull, each having a full complement of
      cranial nerves of good length attached to them. This approach significantly
      increases the length and number of cranial nerves remaining attached to the
      brain, which supports student education. For integration into head and neck
      dissection courses, careful consideration will be required to ensure the necks
      are suitably dissected and to decide whether the cranial nerves are best left
      attached to the skull base or brain.

PMID- 24318013
TI  - Ego identity status, formal operations, and moral development.
AB  - Twenty-six subjects (20 males and 6 females) were administered measures assessing
      ego identity status, level of moral reasoning, and stage of cognitive
      development. Expectations that formal operations would be a necessary but not a
      sufficient condition for the development of post-conventional moral thought and
      for Identity Achievement status were supported. Level of moral thought was also
      found to be positively related to achievement of identity. Individual
      descriptions of subjects with noteworthy patterns of the three variables under
      study were presented. Suggestions for future research included the necessity for
      replication of these findings with a largerN and exploration of the possibility
      that level of social role taking mediates between cognitive development and
      identity (psychosocial) development. 

PMID- 24318014
TI  - Adolescent egocentrism-sociocentrism and self-consciousness.
AB  - A standardized and objectively scored scale of adolescent egocentrism
      sociocentrism (AES) and a self-consciousness scale were given to 44 subjects each
      in the sixth, eighth, tenth, and twelfth grades and college. The AES assesses
      three components of egocentrism including the personal fable, the imaginary
      audience, and general self-focuses, as well as sociocentrism and nonsocial
      subscales. As predicted, the personal fable and imaginary audience declined with
      age. The self-focus subscale showed a curvilinear relationship with age, while,
      again as predicted, sociocentrism increased and nonsocial focuses declined.
      Adolescent egocentrism, as expected, correlated positively with self
      consciousness even with age controlled. Implications for the theories of
      egocentrism and sociocentrism in the adolescent years are discussed. 

PMID- 24318015
TI  - Erikson stage resolution: The relationship between identity and intimacy.
AB  - Ego identity and intimacy statuses were determined for 88 college students, 44
      men and 44 women, and related to each other and to measures of intimacy, loving,
      and liking. As hypothesized, more advanced stages of identity development were
      associated with higher levels of intimacy formation. Further, for both males and
      females, occupational identity development was the primary predictive factor in
      the identity/intimacy stage resolution relationship. 

PMID- 24318016
TI  - Divergent thinking and self-esteem in preadolescents and adolescents.
AB  - The purpose of this study was to explore the relationship between divergent
      thinking and self-esteem in preadolescents and adolescents. A second focus
      pertained to sex differences in the dependent variables. A total of 115 White
      middle class subjects ranging in age from 10-17 years responded to a personal
      data inventory, a self-esteem measure, and a taped auditory free-response
      exercise in divergent thinking. Subjects were categorized for data analysis into
      two age groups, preadolescents and adolescents. Scores were obtained for fluency,
      flexibility, and originality of thought, and for self-esteem. Adolescents were
      significantly more fluent and flexible than preadolescents. The two age groups
      did not differ significantly in orginality or self-esteem. Self-esteem correlated
      significantly with divergent thinking in preadolescents only. Female adolescents
      scored significantly higher on all dependent measures than adolescent males;
      there were no sex differences in preadolescents. Results are discussed from both
      an intra- and interstage developmental perspective on adolescence. 

PMID- 24318017
TI  - Effect of similarity of ego identity status on interpersonal attraction.
AB  - Similarity of ego identity status, assessed by Marcia's four-category
      classification system, was related to interpersonal attraction. Using male and
      female college students as subjects, this study found that (1) while all judges
      preferred targets who had or who are undergoing a crisis to those who have not
      had a crisis, (2) diffuse judges preferred targets with no commitments to those
      with commitments, and (3) judges with commitments preferred a foreclosure target
      more than judges without commitments. Differential evaluations of the targets'
      intelligence, knowledge of current events, adjustment, and morality were also
      found. Results are discussed both in terms of previous research positively
      relating personality similarity to attraction and Erikson's theory of the
      relationship between ego identity development and intimacy in interpersonal
      relations. 

PMID- 24318009
TI  - Abundance and diversity based on amoA genes of ammonia-oxidizing archaea and
      bacteria in ten wastewater treatment systems.
AB  - The abundance and diversity of amoA genes of ammonia-oxidizing archaea (AOA) and
      bacteria (AOB) were investigated in ten wastewater treatment systems (WTSs) by
      polymerase chain reaction (PCR), cloning, sequencing, and quantitative real-time
      PCR (qPCR). The ten WTSs included four full-scale municipal WTSs, three full
      scale industrial WTSs, and three lab-scale WTSs. AOB were present in all the
      WTSs, whereas AOA were detected in nine WTSs. QPCR data showed that AOB amoA
      genes (4.625 * 10(4)-9.99 * 10(9) copies g(-1) sludge) outnumbered AOA amoA genes
      (<limit of detection-1.90 * 10(7) copies g(-1) sludge) in each WTS, indicating
      that AOB may play an important role than AOA in ammonia oxidization in WTSs.
      Interestingly, it was found that AOA and AOB coexisted with anaerobic ammonia
      oxidation (anammox) bacteria in three anammox WTSs with relatively higher
      abundance. In a full-scale industrial WTS where effluent ammonia was higher than
      influent ammonia, both AOA and AOB showed higher abundance. The phylogenetic
      analysis of AOB amoA genes showed that genera Nitrosomonas was the most dominant
      species in the ten WTSs; Nitrosomonas europaea cluster was the dominant major
      cluster, followed by Nitrosomonas-like cluster and Nitrosomonas oligotropha
      cluster; and AOB species showed higher diversity than AOA species. AOA were found
      to be affiliated with two major clusters: Nitrososphaera cluster and
      Nitrosopumilus cluster. Nitrososphaera cluster was the most dominant species in
      different samples and distributed worldwide.

PMID- 24318018
TI  - Correlates of self-concept among black early adolescents.
AB  - This study examines the self-concept of Black eighth-grade students from the
      Midwest in relation to Black acceptance, social intimacy, locus of control, and
      sex-role type. Twenty-eight students high in self-concept were compared with 31
      students whose self-concept was low. As predicted, the high self-concept group
      scored higher than the low self-concept group in intimacy, internality, and
      acceptance of black identity. As also predicted, the high self-concept group had
      a significantly greater number of adolescents with masculine and androgynous sex
      roles than the low self-concept group; Black females with high self-concepts
      included a larger proportion of individuals with androgynous sex roles than low
      self-concept females. However, the prediction that high self-concept males would
      have a larger proportion of masculine sex roles than low self-concept males was
      not supported. The difficult situation of the low self-concept adolescents is
      discussed, along with the implications for intervention. 

PMID- 24318019
TI  - Self-Concept differences between single and married school-age mothers.
AB  - This study examined differences in self-perceptions between single and married
      school-age mothers. The Tennessee Self Concept Scale was administered to 84
      single and married girls who passed through a school-age parent program over a
      two-year period and who chose to keep and rear their babies. Data were subjected
      to a stepwise discriminant analysis to determine an optimal set of variables that
      would distinguish between the two groups. Results indicated that the single
      school-age mothers had extremely low self-concepts, suffered from serious
      emotional problems, had inappropriate coping behaviors, and exhibited significant
      differences from the comparison group on 11 of 26 variables. The single subjects,
      in contrast to their married counterparts, perceived themselves as undersirable,
      unworthy, morally "bad," and unhappy with their behavior, physical selves, and
      social relationships. The married subjects had nominally low self-concepts, with
      their most negative perceptions focused on their moralethical selves. Their most
      positive feelings were expressed about family relationships. 

PMID- 24318020
TI  - Analysis of vitamin D metabolic markers by mass spectrometry: current techniques,
      limitations of the "gold standard" method, and anticipated future directions.
AB  - Vitamin D compounds belong to a group of secosteroids, which occur naturally as
      vitamin D3 in mammals and D2 in plants. Vitamin D is vital for bone health but
      recent studies have shown a much wider role in the pathologies of diseases such
      as diabetes, cancer, autoimmune, neurodegenerative, mental and cardiovascular
      diseases. Photosynthesis of vitamin D in the human skin and subsequent hepatic
      and renal metabolism generate a wide range of transformation products occurring
      over a large dynamic range spanning from picomolar to nanomolar levels. This
      necessitates selective and sensitive analytical methods to quantitatively capture
      these low concentration levels in relevant tissues such as blood. Ideally,
      vitamin D assessment would be performed using a universal and standardized
      analytical method available to clinical laboratories that provides reliable and
      accurate quantitative results for all relevant vitamin D metabolites with
      sufficiently high throughput. At present, LC-MS/MS assays are the most promising
      techniques for vitamin D analysis. The present review focuses on developments in
      mass spectrometry methodologies of the past 12 years. It will highlight
      detrimental influences of the biological matrix, epimer contributions, pitfalls
      of specific mass spectrometry data acquisition routines (in particular multiple
      reaction monitoring, MRM), influence of ionization source, derivatization
      reactions, inter-laboratory comparisons on precision, accuracy, and application
      range of vitamin D metabolites.

PMID- 24318023
TI  - The therapeutic age.

PMID- 24318024
TI  - Toward rigorous but ert models of man.

PMID- 24318022
TI  - Durability of high surface area platinum deposits on microelectrode arrays for
      acute neural recordings.
AB  - The durability of high surface area platinum electrodes during acute
      intracerebral measurements was investigated. Electrode sites with extremely rough
      surfaces were realized using electrochemical deposition of platinum onto silicon
      based microelectrode arrays from a lead-free platinizing solution. The close to
      1000-fold increase in effective surface area lowered impedance, its absolute
      value at 1 kHz became about 7 and 18 % of the original Pt electrodes in vitro and
      in vivo, respectively. 24-channel probes were subjected to 12 recording sessions,
      during which they were implanted into the cerebrum of rats. Our results showed
      that although on the average the effective surface area of the platinized sites
      decreased, it remained more than two orders of magnitude higher than the average
      effective surface area of the original, sputtered thin-film platinum electrodes.
      Sites with electrochemical deposits proved to be superior, e.g. they provided
      less thermal and 50 Hz noise, even after 12 penetrations into the intact rat
      brain. 

PMID- 24318021
TI  - The EGFR signalling system in the liver: from hepatoprotection to
      hepatocarcinogenesis.
AB  - The liver displays an outstanding wound healing and regenerative capacity
      unmatched by any other organ. This reparative response is governed by a complex
      network of inflammatory mediators, growth factors and metabolites that are set in
      motion in response to hepatocellular injury. However, when liver injury is
      chronic, these regenerative mechanisms become dysregulated, facilitating the
      accumulation of genetic alterations leading to unrestrained cell proliferation
      and the development of hepatocellular carcinoma (HCC). The epidermal growth
      factor receptor (EGFR or ErbB1) signaling system has been identified as a key
      player in all stages of the liver response to injury, from early inflammation and
      hepatocellular proliferation to fibrogenesis and neoplastic transformation. The
      EGFR system engages in extensive crosstalk with other signaling pathways, acting
      as a true signaling hub for other growth factors, cytokines and inflammatory
      mediators. Here, we briefly review essential aspects of the biology of the EGFR,
      the other ErbB receptors, and their ligands in liver injury, regeneration and HCC
      development. Some aspects of the preclinical and clinical experience with EGFR
      therapeutic targeting in HCC are also discussed. 

PMID- 24318025
TI  - Humanistic psychology and the trivialization of time.

PMID- 24318027
TI  - Mental health from the Jewish standpoint.

PMID- 24318026
TI  - Empirical science and value assumptions: Lessons from C. G. Jung.

PMID- 24318028
TI  - In time of grief.

PMID- 24318029
TI  - Religion and madness: Schreber'sMemoirs as personal myth.

PMID- 24318030
TI  - The national health planning and resources development act: 1975.

PMID- 24318031
TI  - Myth-conceptions concerning death-related behavior.
AB  - The discussion here has suggested that it is likely that the following beliefs
      are myth conceptions: Living is always prefarable to dying. It is possible for
      people not to "play God." We can be sure that what happens biologically is willed
      by God. God speaks to us only through our biology. Dying occurs only at one point
      in time-at the end of the "terminal period." "Death" or "dead" are more accurate
      labels than "passed on." Persons who are dying know without being told that they
      are dying. Biological death is the most important thing happening when a person
      dies.The goal of achieving understanding of our death-related behavior can be
      facilitated by recognition of myth-conceptions such as these and the previously
      identified myths the acceptance of which may have an impact upon both biological
      and mental or spiritual health of those involved. 

PMID- 24318033
TI  - Studies on the structure of cointegrates between octopine and nopaline Ti
      plasmids and their tumour-inducing properties.
AB  - Stable cointegrates between incRh-1 octopine (Ach5) and nopaline (C58) Ti
      plasmids, present in ten independently isolated Agrobacterium tumefaciens
      strains, showed identical restriction endonuclease patterns. Each cointegration
      event had taken place in the common sequence between the T-regions of both Ti
      plasmids. This illustrates a high preference for this region when used in the
      formation of cointegrates. Four crown gall tissues, obtained after transformation
      of Nicotiana tabacum cells by one of the mutants, were analysed by using Southern
      blot analysis for their T-DNA structure. The borders of T-DNA frequently appeared
      to differ from T-DNA borders previously detected in tumour tissues that had been
      induced by Agrobacterium strain C58 or Ach5. Therefore, it was concluded that
      possibly a less stringent mechanism exists for the integration into plant DNA of
      T-DNA, derived from a composite (octopine/nopaline) T-region than for integration
      of T-DNA from a normal (octopine or nopaline) T-region. 

PMID- 24318034
TI  - In vivo synthesis and processing of cereal lectins.
AB  - The synthesis and processing of cereal lectins was followed in vivo. The initial
      translation products of lectin genes are higher molecular weight (28 K)
      precursors, which are post-translationally processed in a single step into
      authentic lectin polypeptides (23 K). The conversion of precursor into mature
      product is a rather slow process (the precursor has a half life of 36 min) and is
      apparently not a prerequisite for biological activity since the precursor
      exhibits sugar binding activity. Because of the striking resemblances between the
      processing of cereal lectins and vectorial processing of cytoplasmatically made
      chloroplast, mitochondrial and glyoxysomal proteins, vectorial processing of
      cereal lectins might be a means of transporting these proteins through a membrane
      into an extra-cytoplasmic compartment. 

PMID- 24318035
TI  - Identification of T-DNA in the root-inducing plasmid of the agropine type
      Agrobacterium rhizogenes 1855.
AB  - The region of the virulence plasmid of the agropine type Agrobacterium rhizogenes
      1855 (pRi-1855) which is transferred to plant cells upon infection (T-DNA) has
      been identified by means of Southern blot hybridizations with the T-DNA of the
      mannopine type A. rhizogenes 8196. The presence in the plant genome of the pRi
      1855 sequences thus identified is demonstrated in carrot roots derived from
      infection with strain 1855. The T-DNA of pRi-1855 has been mapped by means of
      cloned Eco RI partial digests. Although strongly homologous with each other, the
      cores of the T-regions of the mannopine and agropine Ri plasmids are not colinear
      since the latter contains a central segment of DNA which is absent from the T
      region of pRi-8196. Unexpected homologies between the T-region of pRi-1855 and
      normal carrot DNA have been observed and are discussed here. 

PMID- 24318036
TI  - A simple plant polytene chromosome system, and its use for in situ hybridisation.
AB  - When the cotyledons of Pisum sativum are cultured in the presence of 2-4D, large
      populations of cells with polytene chromosomes are stimulated to enter prophase;
      the use of these chromosome for studies of in situ hybridisation with nucleic
      acids is described. 

PMID- 24318037
TI  - Expression of Rhizobium meliloti genes for nitrogen fixation in Escherichia coli
      minicells: Mapping of the subunit of the nitrogenase reductase.
AB  - An EcoRI fragment of Rhizobium meliloti M2011 which shows homology to Klebsiella
      pneumoniae DNA carrying nifH and nifD was cloned in both orientations into the Cm
      gene of plasmid pACYC184 and expressed in Escherichia coli minicells. Fragment
      specific polypeptides of Mr 12 500, 21 000, 30 000, and 31 000 could be
      identified. By transposon mutagenesis it was shown that two of them (Mr 12 500
      and 21 000) are fusion products with parts of the chloramphenicol
      acetyltransferase. The other two polypeptides are specified by one coding region
      which could be mapped by transposon mutagenesis. There are several reasons
      (homology to Klebsiella nifH, sequence data and molecular weight of the gene
      products) to assume that this coding region represents the R. meliloti nifH gene
      (gene for the subunit of the R. meliloti nitrogenase reductase, RmII). 

PMID- 24318038
TI  - Short-term creatine supplementation does not reduce increased homocysteine
      concentration induced by acute exercise in humans.
AB  - PURPOSE: The purpose of the study is to evaluate the effects of creatine
      supplementation on homocysteine (Hcy) plasma levels after acute exercise in
      humans. METHODS: Twenty-three young (under-20) soccer players were divided into 2
      groups: creatine (Cr)- and placebo (Pla)-supplemented groups. The supplementation
      was performed in double-blind controlled manner using creatine or placebo tablets
      with 0.3 g/kg during 7 days. Before and after 7 days of supplementation, the
      athletes performed an acute high-intensity sprint exercise (two consecutive
      running-based anaerobic sprint test protocol consisted in 6 * 35 m sprint with 10
      s between them). Blood samples were collected before and after 7 days of
      supplementation as well as 0 and 1 h after exercise protocol. RESULTS:
      Homocysteine concentration significant increased (P < 0.05) 1 h after acute
      exercise (18%). Acute exercise also decreased red blood cell S-adenosylmethionine
      (SAM) 30% with no changes in SAM/SAH ratio. Seven days of creatine
      supplementation were able to increase (P < 0.05) plasma creatine concentration
      (Pla 130.1 +/- 21.7 vs Cr 1,557.2 +/- 220.3 MUmol/L) as well as decrease (P <
      0.05) plasma guanidinoacetic acid (33%). Controversially, creatine
      supplementation did not change Hcy plasma level after 7-day supplementation (Pla
      6.9 +/- 0.2 vs Cr 7.2 +/- 0.2 MUmol/L) or after acute exercise (Pla 8.2 +/- 0.3
      vs Cr 8.4 +/- 0.3 MUmol/L). No changes in plasma vitamin B12 and folate as well
      as cysteine and methionine were found. CONCLUSIONS: Seven days of creatine
      supplementation does not avoid increased plasma Hcy induced by acute sprint
      exercise in humans.

PMID- 24318039
TI  - Subthreshold attention-deficit/hyperactivity disorder is associated with
      functional impairments across domains: a comprehensive analysis in a large-scale
      community study.
AB  - This study compared children who experience attention-deficit/hyperactivity
      disorder (ADHD) symptoms but do not meet criteria (i.e., subthreshold ADHD) with
      those with the full syndrome and healthy controls. Presence of ADHD symptoms was
      determined in a nationwide community sample of 921 children, aged 8-11 years. The
      main outcome measures comprised attentional symptoms, comorbidity profiles,
      academic performance, and neurocognitive ability (i.e., ADHD Rating Scale, Child
      Behavior Checklist, Learning Disability Evaluation Scale, and Stroop Color-Word
      Test, respectively). Subthreshold ADHD was equally prevalent in boys and girls,
      and more prevalent in low-income families. Throughout all the outcome
      measurements, subthreshold ADHD was both a significantly milder condition than
      full syndrome ADHD and a significantly more severe condition than non-ADHD
      status. The findings were consistent across the total as well as the subtest
      scores, and after correction for multiple comparisons (p < 0.0017). Children with
      subthreshold ADHD were found to experience significant symptoms and functional
      impairments. The results of this study support the clinical relevance of
      subthreshold ADHD in a childhood population. Subthreshold diagnostic criteria for
      ADHD may be more sensitive in detecting ADHD symptoms in girls than the full
      syndrome criteria, and subthreshold clinical, cognitive, and behavioral symptoms
      of ADHD may occur in a subset of children who are possibly more sensitive to
      their environment. Further consideration about the diagnostic threshold for ADHD
      may particularly benefit girls and children in low-income families.

PMID- 24318040
TI  - Predictors of immigrant children's mental health in Canada: selection, settlement
      contingencies, culture, or all of the above?
AB  - BACKGROUND AND STUDY AIMS: A previous publication from the New Canadian Children
      and Youth Study, a national study of immigrant children and youth in Canada,
      showed a gradient of levels of emotional distress with children from Hong Kong
      (HK) at the most severe end, Filipino children at the least severe, and children
      from the People's Republic of China (PRC) in between. Based on the premise that
      country of origin can be regarded as an index for differing immigration
      trajectories, the current study examines the extent to which arrival
      characteristics, resettlement contingencies and cultural factors account for
      country of origin variations in immigrant children's mental health. Arrival
      characteristics included child's age at arrival, parental education, parental
      fluency in English or French, and assistance from family at arrival. Resettlement
      contingencies included parental mental health, intra-familial conflict,
      settlement stress, separations from parents and child's age when mother started
      working outside the home. Cultural factors included one-child family composition
      and parenting styles. METHODS: A national survey of 2,031 families with at least
      one child between the ages of 4 and 6 or 11 and 13 from HK, the PRC and the
      Philippines was conducted with the Person Most Knowledgeable (PMK) in snowball
      generated samples in 6 different cities across Canada. Predictors of the
      dependent variable, emotional problems (EP), were examined in a hierarchical
      block regression analysis. EP was regressed on ethnic and country of origin group
      in model 1; arrival characteristics were added in model 2; resettlement
      contingencies in model 3 and cultural factors in model 4. RESULTS: The final set
      of predictor variables accounted for 19.3 % of the variance in EP scores among
      the younger cohort and 23.2 % in the older. Parental human and social capital
      variables accounted for only a small amount of the overall variance in EP, but
      there were statistically significant inverse relationships between EP and PMK
      fluency in English or French. Settlement contingencies accounted for a
      significant increase in the explanatory power of the regression equation, net of
      the effects of country of origin and selection characteristics. This block of
      variables also accounted for the Filipino mental health advantage. Levels of
      parent's depression and somatization, harsh parenting, intrafamilial conflict,
      and resettlement stress each varied directly with levels of children's EP.
      Cultural variables made a significant contribution to explaining the variance in
      EP scores. Harsh parenting was significantly associated with increased levels of
      EP in both age groups, and supportive parenting was a mental health protective
      factor for younger children. CONCLUSIONS: Immigrant family human and social
      capital, according to which immigrants are selected for admission to Canada, play
      a relatively small role in determining children's mental health. These effects
      are overshadowed by resettlement contingencies and cultural influences.
      Concentrating on trying to find a formula to select the "right" immigrants while
      neglecting settlement and culture is likely to pay limited dividends for ensuring
      the mental health of children.

PMID- 24318043
TI  - Windswept lower limb deformities in patients with hypophosphataemic rickets.
AB  - BACKGROUND: X-linked hypophosphataemic rickets is an X-linked dominant disorder
      that is secondary to renal phosphate-wasting. Genu varum and/or genu valgum have
      been described as the most common deformities in patients with hypophosphataemic
      rickets. Windswept deformity, which is valgus deformity in one knee and varus
      deformity in the other, was the most common deformity encountered in our
      department. PATIENTS AND METHODS: We collected seven patients who had phenotypic
      and genotypic features consistent with the diagnosis of X-linked
      hypophosphataemic rickets. All presented with windswept lower limb deformity. We
      discuss the phenotypic and genotypic correlation, and the surgical procedures
      applied. Surgical interventions were scheduled to correct the triad of
      appearance, function and biomechanics. RESULTS: Re-alignment orthopaedic measures
      were applied to correct and to restore normal growth and development in these
      children. Post-operative measurements showed dramatic improvements in balance and
      gait. CONCLUSION: The most common deformity seen in patients with
      hypophosphataemic rickets is gradual anetrolateral bowing of the femur combined
      with tibia vara. Windswept lower limb deformity was the most common angular
      deformity in our patients with hypophosphataemic rickets. Baseline skeletal
      surveys and genotypic characterisation were subject to close scrutiny and
      assessment, with the aim of proper diagnosis and treatment. Nevertheless,
      recurrence of deformity is a common sequel and younger patients have a higher
      risk for recurrence.

PMID- 24318042
TI  - De novo mutation in DMD gene in a patient with combined hemophilia A and Duchenne
      muscular dystrophy.
AB  - We report an unusual case of a patient with two combined X-linked diseases,
      severe hemophilia A (HA) and Duchenne muscular dystrophy (DMD), of which only HA
      was hereditary. There was no family history of muscular dystrophy. Genetic
      analysis revealed that HA was caused by the hereditary coagulation factor VIII
      (F8) intron 22 inversion (distal/type I inversion), whereas DMD was caused by a
      de novo deletion in the dystrophin gene. This is the first report of a patient
      with two severe X-linked diseases, of which only HA was hereditary. Despite the
      fact that the probability of acquiring two X-linked abnormalities, one hereditary
      and one de novo, is extremely low, the emergence of such cases indicates that
      genetic testing for distinct X-linked diseases could be of importance in patients
      with hereditary hemophilia. 

PMID- 24318044
TI  - A novel androgen-regulated isoform of the TSC2 tumour suppressor gene increases
      cell proliferation.
AB  - TSC2 (Tuberous sclerosis complex 2) is an important tumour suppressor gene,
      mutations within which are linked to the development of tuberous sclerosis and
      implicated in multiple tumour types. TSC2 protein complexes with TSC1 and blocks
      the ability of the Rheb (Ras homolog enriched in brain) GTPase to activate mTOR
      (mammalian target of rapamycin), a crucial signal transducer which regulates
      protein synthesis and cell growth. Here, we report the characterisation of a
      novel isoform of TSC2 which is under direct control of the ligand-activated
      androgen receptor. TSC2 isoform A (TSC2A) is derived from an internal androgen
      regulated alternative promoter and encodes a 508-amino acid cytoplasmic protein
      corresponding to the C-terminal region of full-length TSC2, lacking the
      interaction domain for TSC1 and containing an incomplete interaction domain
      required for Rheb inactivation. Expression of TSC2A is induced in response to
      androgens and full-length TSC2 is co-ordinately down-regulated, indicating an
      androgen-driven switch in TSC2 protein isoforms. In contrast to the well
      characterised suppressive effect on cell proliferation of full-length TSC2
      protein, both LNCaP and HEK293 cells over-expressing TSC2 isoform A proliferate
      more rapidly (measured by MTT assays) and have increased levels of cells in S
      phase (measured by both Edu staining and FACS analysis). Our work indicates, for
      the first time, a novel role for this well-known tumour suppressor gene, which
      encodes an activator of cell proliferation in response to androgen stimulation. 

PMID- 24318045
TI  - Straightforward RAFT procedure for the synthesis of heterotelechelic
      poly(acrylamide)s.
AB  - Heterotelechelic, hydrophilic polymers with a primary amine and thiol group at
      the alpha- and omega-chain end, respectively, are synthesized via reversible
      addition-fragmentation chain transfer (RAFT) polymerization in a straightforward
      and versatile way and subsequently used for the design of dual-responsive
      polymer/gold nanohybrids. Therefore, a phthalimido-containing chain transfer
      agent (CTA) is synthesized and used for the polymerization of the hydrophilic
      monomers N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide (DMA). After
      polymerization, the trithiocarbonate functionality at the omega-chain end,
      originating from the CTA, is converted into a thiol upon aminolysis. In the next
      step, the phthalimido alpha-chain end is hydrolyzed into a primary amine,
      resulting in heterotelechelic, hydrophilic polymers. End-group conversions are
      monitored by (1)H NMR spectroscopy, MALDI-TOF MS analysis, and UV-Vis
      spectroscopy, confirming that quantitative modifications are obtained during each
      stage. The amino groups of these heterotelechelic polymer chains are modified
      with citraconic anhydride, after which the obtained polymers are grafted with the
      thiol group onto citrate-stabilized gold nanoparticles resulting in the creation
      of dual-temperature- and pH-responsive gold particles.

PMID- 24318046
TI  - The effect of macro- and micro-nutrient fortification of biscuits on their
      sensory properties and on hedonic liking of older people.
AB  - BACKGROUND: Under-nutrition in older adults is widespread. Oral nutritional
      supplement beverages (ONS) are prescribed, yet consumption by older people is
      often insufficient. A variety of supplement formats may improve nutrient intake.
      This study developed protein and micro-nutrient fortified biscuits and evaluated
      their sensory attributes and liking by older people. Two micro-nutrient
      strategies were taken, to match typical ONS and to customise to the needs of
      older people. RESULTS: Oat biscuits and gluten-free biscuits developed contained
      over 12% protein and over 460 kcal 100 g(-1). Two small (40 g) biscuits developed
      to match ONS provided approximately 40% of an ONS portion of micro-nutrients and
      60% of macro-nutrients; however, the portion size was considered realistic
      whereas the average ONS portion (200 mL) is excessive. Biscuits developed to the
      needs of older adults provided, on average, 18% of the reference nutrient intake
      of targeted micro-nutrients. Sensory characteristics were similar between
      biscuits with and without micro-nutrient fortification, leading to no differences
      in liking. Fortified oat biscuits were less liked than commercial oat biscuits,
      partly attributed to flavour imparted by whey protein fortification. CONCLUSION:
      Macro- and micro-nutrient fortification of biscuits could provide an alternative
      fortified snack to help alleviate malnutrition in older adults.

PMID- 24318047
TI  - Uptake of potassium ions by normal and crown-gall-tumor cells of Vinca rosea
      grown in tissue culture.
AB  - Potassium uptake in normal and crown-gall tissue culture cells of Vinca rosea L.
      (Cathalanthus roseus G. Don.) was studied. When grown on White's medium for 14-20
      d, the tumor cells had a higher K(+) content that did the normal cells. At this
      logarithmic stage of growth, the rate of K(+) uptake was greater in normal cells
      than in tumor cells. K(+) uptake in both normal and tumor cells was inhibited
      substantially by 2,4-dinitrophenol but only slightly by oligomycin, NaF, and N,N'
      dicyclohexyl carbodiimide. When the internal K(+) content of the cells was varied
      by growing the tissue in White's medium supplemented with varying concentrations
      of K(+), the rate of K(+) uptake in normal cells increased with decreasing
      internal K(+) concentrations. In contrast both lines of tumor cells failed to
      show this normal increase in the rate of K(+) uptake with decreasing internal
      K(+) concentrations. 

PMID- 24318048
TI  - Blue-light-induced absorbance changes associated with carotenoids in Euglena.
AB  - When treated with blue light, intact cells of Euglena gracilis Klebs var.
      bacillaris Cori, bleached strain W3BUL, show a series of positive peaks at 384,
      411, and 440 nm in the blue-light-minus-dark difference spectrum; bleached strain
      1224-5/24 shows a series of positive peaks at 386, 417, and 448 nm under the same
      conditions. The same changes are observed in a 27,000xg supernatant from
      darkgrown W3. The absorption change appears to be a consequence of shifts in the
      absorption of carotenoids; it is not seen in cells of W3BUL grown on SAN 9789 (4
      chloro-5-(methylamino)-2-(alpha,alpha, alpha-trifluoro-m-tolyl)
      3(2H)pyridazinone) to deplete the carotenoids or in cells of W10BSmL, a mutant
      lacking carotenoids. Inhibitors of flavin-mediated reactions, reductants and
      valinomycin had no effect on the activity of the system. The activity in the
      27,000xg supernatant was associated with material of a molecular weight more than
      2.5*10(6) and was insensitive to heating for 2 min at 100 degrees  C but was
      reduced or eliminated on longer heat treatment or addition of Triton X-100,
      indicating a possible association with membrane material. Photoactivity is
      enriched in the lower density fractions of a flotation gradient, and correlates
      with the zeta-carotene content in all fractions. Similar spectral changes can be
      obtained by comparing the iodine catalyzed cis-to-trans isomerization of zeta
      carotene in a CS2-CHCl3 solvent. The action spectrum for the absorbance change
      shows effectiveness peaks in the 370-390 and 420-448-nm regions, with no marked
      effectiveness past 500 nm. Thus the photosensitizer may not be a carotenoid (at
      least not a normally-occurring C40 carotenoid). These blue-lightinduced
      absorption changes and their action spectra are discussed in relation to such
      blue-light-mediated responses as carotenogenesis, chloroplast development and
      phototaxis. 

PMID- 24318049
TI  - Changes in the isozymic pattern of phosphoenolpyruvate : An early step in
      photoperiodic control of crassulacean acid metabolism level.
AB  - Two major isofunctional forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31)
      have been separated from the leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb
      by acrylamide gel electrophoresis and diethylaminoethyl cellulose techniques: one
      of the forms prevails under long-day treatment (low crassulacean acid metabolism
      level), the other develops under short-day treatment (high Crassulacean acid
      metabolism level). Molecular weights are significantly different: 175.10(3) and
      186.10(3), respectively. These results indicate that two populations of
      phosphoenolyruvate carboxylase are present in the plant, one of which is
      responsible for Crassulacean acid metabolism activity under the control of
      photoperiod.The Crassulacean acid metabolism appears to depend on the same
      endogenous clock that governs other photoperiodically controlled events (e.g.
      flowering). The metabolic and energetic significance of this feature is
      discussed. It is suggested that modification in isozymic composition could be an
      early step in the response to photoperiodism at the metabolic level. 

PMID- 24318050
TI  - Abscisic acid levels and metabolism in the leaf epidermal tissue of Tulipa
      gesneriana L. and Commelina communis L.
AB  - We have shown the presence of abscisic acid (ABA) in abaxial epidermal strips
      taken from Tulipa gesneriana and Commelina communis and that the ABA level rises
      in the epidermis when leaves are water stressed. ABA levels had risen 50% in the
      abaxial epidermis of C. communis 30 min after the leaves lost 10% of their fresh
      weight. Epidermis from both T. gesneriana and C. communis metabolize [(14)C]ABA
      to several products probably including phaseic acid (PA) and dihydrophaseic acid
      (DPA). 

PMID- 24318051
TI  - A radioimmunoassay for abscisic acid.
AB  - We have developed a radioimmunoassay (RIA) for abscisic acid (ABA) in the 0.1 ng
      to 2.5 ng range. Antibodies were obtained from rabbits immunized with ABA bound
      via its carboxyl group to bovine serum albumin. Cross-reactivity studies indicate
      that ABA esters are completely cross-reactive with ABA, while trans, trans
      abscisic acid (t-ABA) phaseic acid (PA) and dihydrophaseic acid (DPA) have much
      lower but significant cross-reactivities. Purification methods which reduce the
      levels of cross-reacting substances are described. 

PMID- 24318052
TI  - Subcellular localization of mannosyl transferase and glycoprotein biosynthesis in
      castor bean endosperm.
AB  - Differential and sucrose density gradient centrifugation have shown that the
      mannosyl transferase present in germinating castor bean endosperm cells which
      catalyses the synthesis of mannosyl-phosphoryl-polyisoprenol is exclusively
      located in the endoplasmic reticulum membrane. This intracellular location was
      confirmed using both ribosome-denuded microsomes isolated in the presence of EDTA
      and rough-surfaced microsomes isolated in the presence of excess Mg(2+) added to
      maintain ribosome-membrane attachment. Separation of organelles following the
      incubation of crude particulate fractions with GDP[(14)C]mannose demonstrated
      that most of the mannolipid thus formed remained associated with the microsomal
      fraction. When organelles were isolated from intact tissue which had previously
      been incubated with GDP[(14)C]mannose, [(14)C]glycoprotein was found to be
      associated with other cellular fractions in addition to the microsomes, in
      particular the glyoxysomes. The kinetics of radioactive labelling of these
      organelles suggest that [(14)C]glycoprotein appears initially in the microsomal
      fraction and subsequently accumulates in the glyoxysomes. Subfractionation of
      isolated, [(14)C]glycoprotein-labelled glyoxysomes established that over 80% of
      the total radioactivity was present in the membrane, while sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis of solubilized glyoxysomal membranes
      showed that the [(14)C]sugar moiety was associated with several, but not all,
      constituent polypeptides. 

PMID- 24318053
TI  - Arsenate as a potential negative selection agent for deficiency variants in
      cultured plant cells.
AB  - Sodium arsenate is toxic to cultured soybean [Glycine max (L.) Merr.] cells,
      killing virtually 100% of the cells during a 24-h exposure at a 1-2 mM
      concentration. However, when growth is previously halted by nitrogen deprivation
      50-100% of the cells survive arsenate treatment. Because of this growthdependent
      toxicity, arsenate has promise as a negative selection agent for cultured plant
      cells. Using arsenate (2 mM) I was able to select from among 2*10(7) cells a cell
      line with a growth requirement for an amino acid mixture. This trait was
      maintained through 9 months of passage but then was lost. 

PMID- 24318055
TI  - The kinetics of bidirectional growth of stem sections from etiolated pea
      seedlings in response to acid, auxin and fusicoccin.
AB  - Growth in length and diameter of abraded stem sections from etiolated pea (Pisum
      sativum L.) seedlings was monitored continuously using a double laser optical
      level auxanometer system. Acidic solutions (pH 4.0-4.5) induced rapid elongation
      accompanied by lateral shrinkage (up to 8% of the initial diameter). The
      shrinkage phase lasted for 30-45 min. Pretreatment with permeant solutes (KCl,
      NaCl, sucrose or glucose) prevented lateral shrinkage, while pretreatment with
      the impermeant solute, polyethylene glycol, did not block lateral contraction in
      response to acid. A slight turgor step-up given during the shrinkage phase
      inhibited lateral shrinkage and increased the elongation rate. Visual observation
      confirmed that shrinkage occurred and that the same region of the stem that
      contracted in diameter also elongated. It is proposed that lateral shrinkage
      results from a decrease in turgor pressure during acid-stimulated elongation.
      Elongation induced by auxin and fusicoccin (FC) was also accompanied by a
      decrease in the diameter; this decrease could be prevented by pretreatment with
      KCl or glucose. Thus, the early phase of auxin and FC action is "acid-like".
      However, the shrinkage is of shorter duration (14-20 min) and it is less drastic
      (ca. 2%). In addition, FC caused lateral expansion after a 20-min lag period in
      stems pretreated with KCl. The results are consistent with an acid-growth
      mechanism during the early phase (first 20-40 min) of the responses to both auxin
      and FC. It is suggested that enhanced osmoregulation subsequently inhibits
      further lateral shrinkage and helps to maintain steady-state growth. FC, unlike
      auxin, may alter the anisotropic character of the wall. 

PMID- 24318054
TI  - Utilization of enzyme markers to determine the location of plasma membrane from
      Pisum epicotyls on sucrose gradients.
AB  - Using linear sucrose gradients, particulates derived from pea (Pisum sativum L.
      cv. Alaska) epicotyls have been fractionated and examined for marker enzyme
      activity. The coincidence of three reputed plasma-membrane markers [cellulase (EC
      3.2.1.4), K(+)-stimulated Mg(2+)-ATPase, and glucan synthetase] at the same
      position on sucrose density gradients, in combination with electron microscopic
      evidence reported by G. Shore and G. Maclachlan (J. Cell Biol. 64, 557-571;
      1975), indicates that plasma membrane of pea epicotyl has a buoyant density of
      about 1.13 g/cm(3). This density disagrees with those usually reported for plant
      plasma membranes and also with recent reports for Pisum. It is, however, shown to
      be distinct from the equilibrium densities of enzymic markers for particulate
      components derived from Pisum endoplasmic reticulum (1.10-1.11 g/cm(3)), Golgi
      (1.12 g/cm(3)) and mitochondria (1.18 g/cm(3)). Furthermore, other recent
      literature indicates that the 1.13 g/cm(3) buoyant density may be characteristic
      of the plasma membrane of many members of the Leguminosae. Our data indicate that
      the conditions of differential centrifugation (time, centrifugal force), coupled
      with the amount of protein utilized, affect the resolution and interpretation of
      profiles of marker enzymes on sucrose gradients (e.g. glucan synthetase and K(+)
      stimulated Mg(2+)-ATPase were sometimes found to be associated not only with
      particles of 1.13 g/cm(3) density, but with particles of higher densities as
      well). Particulate cellulase was found to be associated only with particles with
      equilibrium densities of about 1.13 g/cm(3). Cellulase thus proved to be the most
      useful marker for establishing a differential centrifugation regime which would
      permit examination of the 1.13 g/cm(3) particulate components with minimal
      contamination by particles of higher densities. 

PMID- 24318056
TI  - A glycoprotein associated with the acquisition of the self-incompatibility system
      by maturing stigmas of Brassica oleracea.
AB  - Iso-electric focusing of extracts derived from stigmatic homogenates of Brassica
      oleracea reveals that the mature stigma possesses large quantities of a
      glycoprotein not present in earlier stages of development in the bud. Pollen
      germination experiments carried out in parallel with the biochemical tests
      suggest that the appearance of this glycoprotein, which has an isoelectric point
      of pH 5.8, is coincident with the development of the self-incompatibility
      response. The site of this protein, and the role it may play in pollen-stigma
      interactions are discussed in terms of current models of the self-incompatibility
      system in Brassica. 

PMID- 24318057
TI  - Identification of gibberellins in the rice plant and quantitative changes of
      gibberellin A19 throughout its life cycle.
AB  - The major endogenous gibberellin (GA) in shoots, roots and ears of the rice
      plant, Oryza sativa L. japonica cv. Nihonbare, was identified as GA19 by combined
      gas liquid chromatography-mass spectrometry (GC-MS) and GC-selected ion current
      monitoring (GC-SICM). Another GA present in these tissues in small quantity was
      tentatively identified as GA1 by GC-SICM, and GA4 may be present in the seeds
      (kernels) of 3rd-leaf-stage seedlings. Using GC-SICM, the GA19 content was
      quantified throughout the life cycle of rice plants. It was found to reach high
      levels (ca. 10-15 MUg/kg fresh weight) in 3rd-leaf seedlings, at panicle
      initiation (shoots), and during heading and anthesis (ears). The levels of GA19
      in Oryza sativa indica cv. T-136 underwent changes closely similar to those found
      in Nihonbare. The growth-promoting activity in rice of exogenous GA19 is
      generally considerably less than that of GA1. It therefore seems possible that
      GA19 functions as a "pool GA". The level of active GAs such as GA1 may be
      regulated by the rate of biosynthesis of GA19 or its metabolic conversions. 

PMID- 24318058
TI  - Induction of ethylene formation in bean (Phaseolus vulgaris) hypocotyl segments
      by preparations isolated from germ tube cell walls of Uromyces phaseoli.
AB  - Hypocotyl segments of Phaseolus vulgaris produce ethylene at pH 8.0 and ethane at
      pH 5.4. Ethylene formation, but not ethane formation, was stimulated by
      methionine, while alpha-linolenic acid stimulated both ethylene and ethane
      formation. Detached primary leaves of var. "Favorit" (susceptible to Uromyces
      phaseoli) show no enhanced ethylene formation, whereas primary leaves from var.
      017 (hypersensitive) exhibit two distinct ethylene peaks ca. 10 h and 50 h after
      inoculation with U. phaseoli.Cell wall preparations from uredospore germ tubes of
      U. phaseoli strongly stimulate ethylene formation in hypocotyl segments of the
      hypersensitive var. 017 but to a much lesser extent in the susceptible var.
      Favorit. 

PMID- 24318059
TI  - Uridinediphosphate-glucose: Isovitexin 7-O-glucosyltransferase from barley
      protoplasts: Subcellular localization.
AB  - Protoplasts isolated from 6-d-old primary leaves of barley (Hordeum vulgare L.)
      contain an enzyme which transfers the glucosyl moiety of uridine
      diphosphateglucose to isovitexin, resulting in the formation of saponarin, the
      major flavonoid of barley. Purified chloroplasts isolated from protoplasts
      contained less than 2% of the total glucosyltransferase activity. These
      chloroplasts were 97% intact, based on ribulose-bisphosphate-carboxylase
      activity. Similarly low levels of glucosyltransferase activity were found in
      mitochondria and microbody or microsomal preparations from protoplasts. The
      soluble fraction (cytosol) contained at least 93% of the isovitexin 7-O
      glucosyltransferase activity. 

PMID- 24318060
TI  - Structure and association of wall fibrils produced by regenerating tobacco
      protoplasts.
AB  - A study has been made of the wall fibrils produced by tobacco protoplasts, using
      scanning electron microscopy in conjunction with negative staining. It has been
      shown that the fibres seen in scanning electron microscopy correspond to
      aggregates of microfibrils. These aggregates are only visible where they are
      lifted clear of the protoplast surface. Negative staining of fixed protoplasts
      shows that the aggregation of microfibrils into the fibres visible in scanning
      electron microscopy is probably produced by air-drying. Gentle disruption of
      microfibrils produces both random broken fragments and bundles of short pieces of
      fibrillar material about 60 nm in length. This material is present in undisrupted
      young walls, but not in undisrupted older walls. The microfibrils in young walls
      seem much more fragile and liable to breakage than those in older walls. These
      results are discussed in terms of the interpretation of scanning electron
      microscope images and the mechanism of cellulose microfibril formation by higher
      plants. 

PMID- 24318061
TI  - Pollen-pistil interaction in Brassica oleracea : Events prior to pollen
      germination.
AB  - Quantitative studies of the adhesion of pollen grains to the stigma in Brassica
      oleracea revealed that self-pollen is initially less firmly bound than cross
      pollen. The pollen grain tryphine, believed to be important in the adhesion
      process, has been shown to differ in mobility following self- and cross
      pollination when observed using fluorescent probes. The hydration of the pollen
      grains has been investigated in vitro by measuring the changes in shape, volume
      and fresh weight of the imbibing grains. Whilst little change in volume could be
      detected there was a considerable increase in fresh weight together with a change
      of shape. The significance of these events, which occur prior to pollen
      germination, is discussed in relation to their effect upon subsequent germination
      and expression of self-incompatibility. 

PMID- 24318062
TI  - Glycoprotein conformation in plant cell walls : Circular dichroism reveals a
      polyproline II structure.
AB  - The major structural glycoprotein of the cell wall of Chlamydomonas reinhardii
      has a protein core, at least 50% of which is in the unusual polyproline II
      conformation. This has been demonstrated by examining the circular dichroism of
      the cell wall, its constituent glycoproteins, and thermolysin released wall
      glycopeptides. One of these glycopeptides, T2, has a high hydroxyproline and
      sugar content, and possesses upward of 85% polyproline II structure. The main
      extracellular matrix glycoprotein therefore has a rigid, rod-like structure and
      the significance of this and its relation to higher plant cell wall glycoproteins
      is discussed. The unusual conformation appears to confer great stability on the
      glycoprotein as it is unchanged either by certain denaturing agents or during the
      transition from protomer to assembled cell wall. 

PMID- 24318063
TI  - The effect of divalent metal ions on the activity of Mg(++) depleted ribulose-1,5
      bisphosphate oxygenase.
AB  - Ribulose-1,5-bisphosphate carboxylase-oxygenase is deactivated by removal of
      Mg(++). The enzyme activities can be restored to a different extent by the
      addition of various divalent ions in the presence of CO2. Incubation with Mg(++)
      and CO2 restores both enzyme activities, whereas, the treatment of the enzyme
      with the transition metal ions (Mn(++), Co(++), and Ni(++)) and CO2 fully
      reactivates the oxygenase: however, the carboxylase activity remains low. In
      experiments where CO2-free conditions were conscientiously maintained, no
      reactivation of RuBP oxygenase was observed, although Mn(++) ions were present.
      Other divalent cations such as Ca(++) and Zn(++), restore neither the carboxylase
      nor the oxygenase reaction. Furthermore, the addition of Mn(++) to the Mg(++) and
      CO2 preactivated enzyme significantly inhibited carboxylase reactions, but
      increased the oxygenase reaction. 

PMID- 24318064
TI  - The effect of deuterium oxide on protein turnover in Lemna minor.
AB  - Lemna minor fronds transferred to a sterile culture medium containing 50% (v/v)
      deuterium oxide ((2)H2O) rapidly undergo a loss of soluble protein with a
      corresponding increase in free amino acids. The loss of protein is due to two
      factors: (i) the inhibition of protein synthesis for 4 h followed by a slower
      rate of synthesis than normal, (ii) a rapid 9-10 fold increase in protein
      degradation. In plants grown for longer periods (3-6 days) in 50% (2)H2O medium,
      protein synthesis is inhibited by 20% and the rate constant of degradation is 2-3
      times that measured in fronds growing in normal (H2O containing) complete medium.
      The initial loss of protein is not due to the breakdown of any specific protein
      fraction. Investigation of several enzymes indicates that all proteins are
      catabolised in response to (2)H2O treatment. The implications of these results
      with regard to the interpretation of density-labelling experiments are discussed.

PMID- 24318065
TI  - Enzymes of asparagine synthesis in maize roots.
AB  - An asparagine synthetase which is active with either glutamine or NH 4 (+) has
      been found in maize (Zea mays L.) roots. Unlike the enzyme obtained from legume
      cotyledons, the maize-root enzyme is only slightly more efficient with glutamine
      (Km, 1.0 mM) than with NH 4 (+) (Km, 2.0-3.0 mM). The activity of this enzyme is
      higher in the mature root than in the root-tip region, i.e. root cells develop a
      capacity to make asparagine from glutamine or NH 4 (+) as they mature. beta
      Cyanoalanine synthetase is also present in maize roots. The apparent Km for
      cysteine is 2.6 mM and for cyanide is 0.57 mM. The enzyme is more active in the
      root tip than in mature root tissue. Thus, if asparagine were made in the root
      tip, the cyanide pathway could represent the mechanism of synthesis. It is our
      contention, however, that this potential is not realized under normal conditions
      because (14)C-experiments performed previously have indicated a limited
      availability of both CN and cysteine in the maize root. 

PMID- 24318066
TI  - Regeneration of whole plants from callus culture of diverse genetic lines of
      Pisum sativum L.
AB  - Sixteen genetic lines of peas were screened for their ability to regenerate whole
      plants from callus cultures. Epicotyl sections from germinating seeds were placed
      on callus-inducing medium; the resulting callus was subcultured monthly and was
      tested every other month for its regeneration ability. Six lines were found that
      would regenerate after 2 months' growth as callus. Four of these continued to
      regenerate after 4 months and, of these, two after 6 months. The cultivars
      "Frosty" and "Alaska" were among the lines that would not regenerate at all. 

PMID- 24318068
TI  - Erratum.

PMID- 24318067
TI  - Separation of cell enlargement and division in bean leaves.
AB  - A method is presented for inducing cell enlargement in intact leaves and leaf
      strips of Phaseolus vulgaris L. without the complication of cell division.
      Primary bean leaves complete cell division and stop growing after 10 d in dim red
      light. Transfer to white light induces expansion (50% in 24 h) which is entirely
      the consequence of cell enlargement. Leaf strips from red-light-grown seedlings
      placed in white light and provided external solutes (10 mM KCl+10 mM sucrose)
      expand at the same rate as intact leaves in the light. This system makes possible
      future investigation of the mechanism of leaf cell enlargement. 

PMID- 24318069
TI  - Solid-phase microextraction with a graphene-composite-coated fiber coupled with
      GC for the determination of some halogenated aromatic hydrocarbons in water
      samples.
AB  - In this work, a graphene composite was coated onto etched stainless-steel wire
      through a sol-gel technique and it was used as a solid-phase microextraction
      (SPME) fiber. The prepared fiber was characterized by SEM, which revealed that
      the fiber had a highly porous structure. The application of the fiber was
      evaluated through the headspace SPME of five halogenated aromatic hydrocarbons
      (chlorobenzene, bromobenzene, 1,3-dichlorobenzene, 1,2-dichlorobenzene, and 1,2,4
      trichlorobenzene) in water samples followed by GC with flame ionization
      detection. The main factors influencing the extraction efficiency, including
      headspace volume, extraction time, extraction temperature, stirring rate, ionic
      strength of sample solution, and desorption conditions, were studied and
      optimized. Under the optimum conditions, the linearity of the method ranged from
      2.5 to 800.0 MUg/L for 1,2,4-trichlorobenzene and from 2.5 to 500.0 MUg/L for
      chlorobenzene, bromobenzene, 1,3-dichlorobenzene, and 1,2-dichlorobenzene, with
      the correlation coefficients (r) ranging from 0.9962 to 0.9980, respectively. The
      LODs (S/N = 3) of the method for the analytes were in the range between 0.5 and
      1.0 MUg/L. The recoveries of the method for the analytes obtained for the spiked
      water samples at 50.0 and 250.0 MUg/L were from 76.0 to 104.0%. 

PMID- 24318070
TI  - Intra-articular calcifications following arthroscopic ACL reconstruction:
      prevalence and possible significance.
AB  - PURPOSE: The goal of our study was to determine the frequency of intra-articular
      calcifications on initial postoperative radiographs following arthroscopic ACL
      reconstruction, describe their appearance, hypothesize their etiology, and
      determine their significance. MATERIALS AND METHODS: Review of records and post
      operative radiographs for individuals undergoing arthroscopic ACL reconstruction
      at our institution identified 758 knees between November 2002 and April 2010. All
      patients underwent femoral and tibial tunnel drilling regardless of graft source.
      All but 23 underwent notchplasty. RESULTS: Intra-articular calcifications on
      initial postoperative radiographs were observed in 252 knees. The majority of
      calcifications were curvilinear, paralleling the posterior femoral condyles.
      Nineteen of the patients with calcifications on initial studies had repeat
      radiographs within 6 years. The calcifications resolved in every case.
      CONCLUSIONS: This study shows that intra-articular calcifications are a common
      finding on initial post-operative radiographs following ACL reconstruction. We
      feel they are of doubtful clinical significance, and in our limited experience,
      they eventually resolve. They should not be confused with chondrocalcinosis or
      vascular calcification.

PMID- 24318072
TI  - Multiple painless masses: periostitis deformans secondary to fluoride
      intoxication.

PMID- 24318071
TI  - Use of 3D MR reconstructions in the evaluation of glenoid bone loss: a clinical
      study.
AB  - OBJECTIVE: To assess the ability of 3D MR shoulder reconstructions to accurately
      quantify glenoid bone loss in the clinical setting using findings at the time of
      arthroscopy as the gold standard. MATERIALS AND METHODS: Retrospective review of
      patients with MR shoulder studies that included 3D MR reconstructions (3D MR)
      produced using an axial Dixon 3D-T1W-FLASH sequence at our institution was
      conducted with the following inclusion criteria: history of anterior shoulder
      dislocation, arthroscopy (OR) performed within 6 months of the MRI, and an
      estimate of glenoid bone loss made in the OR using the bare-spot method. Two
      musculoskeletal radiologists produced estimates of bone loss along the glenoid
      width, measured in mm and %, on 3D MR using the best-fit circle method, which
      were then compared to the OR measurements. RESULTS: There were a total of 15
      patients (13 men, two women; mean age, 28, range, 19-51 years). There was no
      significant difference, on average, between the MRI (mean 3.4 mm/12.6 %; range, 0
      30 %) and OR (mean, 12.7 %; range, 0-30 %) measurements of glenoid bone loss (p =
      0.767). A 95 % confidence interval for the mean absolute error extended from 0.45
      2.21 %, implying that, when averaged over all patients, the true mean absolute
      error of the MRI measurements relative to the OR measurements is expected to be
      less than 2.21 %. Inter-reader agreement between the two readers had an IC of
      0.92 and CC of 0.90 in terms of percentage of bone loss. CONCLUSIONS: 3D MR
      reconstructions of the shoulder can be used to accurately measure glenoid bone
      loss.

PMID- 24318073
TI  - Mass spectrometry analysis of nitrotyrosine-containing proteins.
AB  - Oxidative stress plays important roles in a wide range of diseases such as
      cancer, inflammatory disease, neurodegenerative disorders, etc. Tyrosine
      nitration in a protein is a chemically stable oxidative modification, and a
      marker of oxidative injuries. Mass spectrometry (MS) is a key technique to
      identify nitrotyrosine-containing proteins and nitrotyrosine sites in endogenous
      and synthetic nitroproteins and nitropeptides. However, in vivo nitrotyrosine
      containing proteins occur with extreme low-abundance to severely challenge the
      use of MS to identify in vivo nitroproteins and nitrotyrosine sites. A
      preferential enrichment of nitroproteins and/or nitropeptides is necessary before
      MS analysis. Current enrichment methods include immuno-affinity techniques,
      chemical derivation of the nitro group plus target isolations, followed with
      tandem mass spectrometry analysis. This article reviews the MS techniques and
      pertinent before-MS enrichment techniques for the identification of nitrotyrosine
      containing proteins. This article reviews future trends in the field of
      nitroproteomics, including quantitative nitroproteomics, systems biological
      networks of nitroproteins, and structural biology study of tyrosine nitration to
      completely clarify the biological functions of tyrosine nitration.

PMID- 24318074
TI  - The role of lifestyle interventions in the prevention of gestational diabetes.
AB  - Gestational diabetes is associated with adverse pregnancy outcomes, increased
      costs, and long-term risk of type 2 diabetes mellitus (T2DM) in the mother.
      Observational data have shown an association between reduced weight gain, healthy
      eating, and physical activity and reduced rates of gestational diabetes mellitus
      (GDM). Despite this, most randomized controlled trials of lifestyle interventions
      to prevent GDM have been negative. Dietary approaches appear to be more
      successful than exercise or a combination of diet and exercise at decreasing GDM.
      Reasons for negative studies may include lack of power, lack of intervention
      uptake, and severity of placenta mediated insulin resistance. Future studies
      should be powered for a reduction in GDM, monitor lifestyle changes closely, and
      include a psychological component in the intervention.

PMID- 24318075
TI  - Adolescents who work: Effects of part-time employment on family and peer
      relations.
AB  - Research on adolescents has ignored a setting in which significant numbers of
      young people spend significant amounts of time: the workplace. The increasing
      participation of high school students in the part-time labor force raises a
      number of questions about the impact of such employment on family and peer
      relations. Questionnaire data from a descriptive study of 531 tenth- and eleventh
      graders indicate that (a) working attenuates time spent with family, but not
      with peers; (b) girls, but not boys, may enter the work force in part as a result
      of weaker emotional ties to their parents; (c) working has negligible impact on
      the quality of family and peer relationships; (d) despite substantial incomes,
      workers do not have complete autonomy over their expenditures, nor do working and
      money-making lead to increased autonomy in other areas; and (e) the workplace is
      not a source of close personal relationships with others. Taken together, these
      findings suggest that working does not have a substantial immediate impact on the
      adolescent's relations with others. Possible long-range effects are briefly
      noted. 

PMID- 24318076
TI  - The effect of early labor market experience upon internal-external locus of
      control among young male workers.
AB  - This study examined the influence of some personal and labor market factors on
      changes in internal-external control among young male workers. Utilizing 960
      respondents from the National Longitudinal Surveys of Labor Market Experience's
      national sample for young men, multiple regression analysis, and an abbreviated
      version of the Rotter Internal-External Control Scale, this study found that
      labor market success, race, and employment in the private sector enhance feelings
      of internal control during the transition between school and work. 

PMID- 24318077
TI  - Personality competence in black male adolescents.
AB  - This study explores the nature and antecedents of personality competence in Black
      male adolescents. Community college teachers were first asked to describe, in
      interview and Q-Sorts, the qualities they believed characterized competent young
      Black men. There was considerable agreement between Black and White teachers, and
      the ratings of both correlated highly with the California Q-Sort description of
      the Optimally Adjusted Personality described by White clinicians. In the second
      phase of the study, particularly competent young Black males, nominated by these
      teachers, were compared with average Black students on the same Q-Sort, a
      vocabulary test, and Offer's Self-Image Questionnaire. In general, the
      personality qualities of the two groups are more alike than different, though the
      more competent males are more inner- than outer-directed; more sensitive to
      personal qualities than to outward appearances and their own acceptability to
      others. They are more ambitious, more motivated for success, and seem to strive
      more vigorously, perhaps even to sidestep some moral precepts (indicated by lower
      Offer Morality score). The competent young Black males differ importantly,
      although not always significantly, from their more average peers in being earlier
      and more thoroughly committed to a work ethic; they come from more stable homes;
      have more social contact with the White culture; and are more likely to be first
      or only children. Although the study intended to contrast more and less competent
      adolescents within the Black culture, it is speculated that both the nature and
      antecedents of competence are probably transracial. Additional analyses show that
      competence can be empirically distinguished from social desirability, though the
      two concepts are related. 

PMID- 24318078
TI  - Developing a measure of student deviance: A research note.
AB  - University students are expected to defer to the authority of the formal rules of
      a university and to any symbols of that authority. A student engaging in open
      confrontation of the authority structure is violating the norms of the student
      role. While there are many measures of student support for protest, existing
      measures are inappropriate as generalized measures of deviance in the student
      role. This research develops two measures: Attitudinal Support for Confrontation
      (ASC) and Behavioral Support for Confrontation (BSC). Results of tests of
      reliability, convergent validity, and theoretical relevance show that (1)
      responses are internally consistent; (2) both measures tap a confrontation
      continuum; (3) descriptive characteristics of ASC supporters are comparable to
      other attitudinal protest measures; and (4) there are differences between
      behavioral and attitudinal support patterns. 

PMID- 24318079
TI  - An examination of types of delinquency through path analysis.
AB  - Relationships between father's occupation, delinquent peer association, tendency
      to neutralize, and self-reported delinquency are explored in a path model. Self
      reported delinquency are categorized into Minor, Predatory, and Aggressive
      delinquency. The effect of this division is analyzed among Mexican Americans and
      Anglo college students (N=694). The structure of the resulting path models
      remained similar across these subsamples, although there was some variation in
      the strength of the relationships. The effect of father's occupation was minimal.
      The strongest relationships were between neutralization and delinquency,
      controlling for delinquent peers and for father's occupation, which decreased as
      the seriousness of the delinquency increased. Additionally, neutralization was
      more strongly related to delinquency among Anglos than among Mexican Americans,
      explaining 39% of the variation in delinquency among Anglos, but only 28% among
      Mexican Americans. Association with delinquent peers, however, was more strongly
      related to delinquency among Mexican Americans. 

PMID- 24318080
TI  - Moral maturity and behavior: Failure to find a link.
AB  - The question addressed is whether individuals operating at the Postconventional
      level of moral reasoning behave appreciatively different from those functioning
      at lower moral maturity levels. The types of behaviors reported in the literature
      are classified in five areas: resistance to temptation, resistance to social
      influence/authority, student activism, prosocial behavior, and antisocial
      behavior. The data suggest that evidence linking Kohlbergian moral development to
      differential behaviors is remote. However, the link between moral reasoning and
      behavior is not positively nonexistent. There remain several factors which
      probably affect the findings in all five behavioral categories, especially the
      sparsity of subjects at the principled level and the limited range of behaviors
      investigated. 

PMID- 24318081
TI  - Toward a contemporary tradition for menarche.
AB  - A cultural tradition to acknowledge a girl's first menstrual period is proposed
      in order to overcome the negative connotation of the event. Three basic questions
      regarding such a tradition are addressed: Who would participate? What would it
      mean? What type of activity should it be? A research team consisting of a
      psychologist, a nurse, and a social worker suggests answers based on their
      interviews with mothers and daughters, as well as their collection of menarche
      anecdotes from women psychologists. 

PMID- 24318082
TI  - Validation of a self-administered instrument to assess stage of adolescent
      development.
AB  - Drawings were made from Tanner's photographs illustrating five stages of
      development each for male genitalia, testicular size, male pubic hair, female
      breasts, and female pubic hair. Forty-seven females and forty-eight males aged 12
      16 years indicated on questionnaires which stage they were most like, and
      answered other questions related to their physical development. Afterwards they
      were examined by physicians who had not seen their answers. Pearson correlation
      coefficients were 0.6 or above for the physician's observations compared with the
      adolescents' answers for the drawings, with the exception of testicular size.
      Answers to questions concerning amount of underarm hair and general development
      also yielded high correlations. 

PMID- 24318083
TI  - The association of PTSD with physical and mental health functioning and
      disability (VA Cooperative Study #569: the course and consequences of
      posttraumatic stress disorder in Vietnam-era veteran twins).
AB  - PURPOSE: To assess the relationship of posttraumatic stress disorder (PTSD) with
      health functioning and disability in Vietnam-era Veterans. METHODS: A cross
      sectional study of functioning and disability in male Vietnam-era Veteran twins.
      PTSD was measured by the Composite International Diagnostic Interview; health
      functioning and disability were assessed using the Veterans RAND 36-Item Health
      Survey (VR-36) and the World Health Organization Disability Assessment Schedule
      2.0 (WHODAS 2.0). All data collection took place between 2010 and 2012. RESULTS:
      Average age of the 5,574 participating Veterans (2,102 Vietnam theater and 3,472
      non-theater) was 61.0 years. Veterans with PTSD had poorer health functioning
      across all domains of VR-36 and increased disability for all subscales of WHODAS
      2.0 (all p < .001) compared with Veterans without PTSD. Veterans with PTSD were
      in poorer overall health on the VR-36 physical composite summary (PCS) (effect
      size = 0.31 in theater and 0.47 in non-theater Veterans; p < .001 for both) and
      mental composite summary (MCS) (effect size = 0.99 in theater and 0.78 in non
      theater Veterans; p < .001 for both) and had increased disability on the WHODAS
      2.0 summary score (effect size = 1.02 in theater and 0.96 in non-theater
      Veterans; p < .001 for both). Combat exposure, independent of PTSD status, was
      associated with lower PCS and MCS scores and increased disability (all p < .05,
      for trend). Within-pair analyses in twins discordant for PTSD produced consistent
      findings. CONCLUSIONS: Vietnam-era Veterans with PTSD have diminished functioning
      and increased disability. The poor functional status of aging combat-exposed
      Veterans is of particular concern.

PMID- 24318084
TI  - Quality of life assessed with EQ-5D in patients undergoing glioma surgery: what
      is the responsiveness and minimal clinically important difference?
AB  - PURPOSE: To evaluate the responsiveness of EQ-5D 3L in patients undergoing
      intracranial glioma surgery and estimate the minimal clinically important
      difference (MCID). MATERIALS AND METHODS: EQ-5D 3L index values from 164 patients
      who underwent glioma surgery in the period 2007-2012 were analysed.
      Responsiveness and MCID were estimated using a combination of distribution-based
      and anchor-based methods. Karnofsky performance status served as an anchor.
      RESULTS: Patients who improved functionally did not report significantly higher
      EQ-5D 3L scores post operatively with a standardized response mean (SRM) of 0.04
      (p = 0.13). Patients who deteriorated functionally reported significantly lower
      EQ-5D 3L scores post operatively with a SRM of 0.72 (p < 0.001). With different
      approaches, we determined a range of MCID values from 0.13 to 0.15. CONCLUSIONS:
      EQ-5D 3L is responsive to changes when glioma patients are deteriorating
      functionally after surgery but not responsive when the patients are improving.
      The MCID values for EQ-5D 3L in glioma surgery seem higher than reported MCID
      values for other types of cancers.

PMID- 24318086
TI  - Private health and the public mind.

PMID- 24318085
TI  - Framework to assess the effects of using patient-reported outcome measures in
      chronic care management.
AB  - PURPOSE: The inclusion of patient-reported outcome measures (PROMs) in the
      routine clinical care of chronically ill patients has the potential to add
      valuable information about the impact of the disease and its treatment and
      promotes effective patient self-management in which patients become more active
      participants in their own care. PROMs provide clinicians with timely information
      on patients' symptoms as well as functional and emotional status. PROMs are a
      useful tool for enhancing patient-clinician communication. METHODS: We develop a
      conceptual framework describing the potential effects of the use of PROMs in
      chronic care management. The framework summarizes insights from the methods for
      evaluating the clinical effectiveness and methods for the health technology
      assessment of diagnostic technologies and results from the relevant studies.
      RESULTS: The framework describes potential effects, from proximal to distal,
      including communication (patient-clinician, patient-relative, clinician
      clinician, and clinician-relative), engaging patients in shared clinical decision
      making, patient management (clinician management and patient self-management),
      and patient outcomes. Important potential effects also include enhancement in
      patient activation as well as improvements in clinician and patient satisfaction,
      and patient adherence to recommended treatment. Previous frameworks have
      described patient-physician communication, patient satisfaction, and health
      outcomes. Our framework adds unique domains, including patient engagement,
      patient activation, shared clinical decision making, and patient self-management.
      CONCLUSIONS: The framework can be used as a tool to guide the development of
      interventions to improve chronic care management through the use of PROMs.

PMID- 24318087
TI  - Culture, ethnicity, and mental health.
AB  - CONCLUSION: This is the important point, I think, both in the research field and
      in the research-policy-administrative-political field that might be characterized
      by the collective interests of people in these fields. Our discussions do not
      suggest unalterable directions for our efforts, and whatever answers we may come
      up with do not suggest final conclusions. If we are able to trust one another and
      our institutions-and I feel that trust is one of the key issues in any discussion
      about mental-health topics-then we have to admit that perhaps we are all correct.
      And our progress in the area of ethnicity, culture, and mental health will be
      promoted by our continued co-operation.

PMID- 24318088
TI  - Pastoral psychotherapy, the fee-for-service model, and professional identity.

PMID- 24318089
TI  - Masturbation: Vice or virtue?

PMID- 24318090
TI  - The image of the Devil in C. G. Jung's psychology.

PMID- 24318091
TI  - George christian anderson: 1907-1976.

PMID- 24318092
TI  - Lawyer and pastoral counselor: A team for divorce counseling.
AB  - CONCLUSION: The dull thud of the gavel ends a way of life. At the same time, a
      new status that is both easier and more difficult is created. Gone is the strain
      of an unhappy home full of bitterness, recriminations, and unhappy memories that
      can be recalled and repeated like peeling off the layers of an onion. On the
      horizon is a new way life, full of optimism and aspirations. Yet this new life is
      not without its own hazards. Life is like a river that may run smooth for a while
      but that ultimately will face rapids. We can almost hear the rapids in the
      distance and know they are there. We don't know now exactly what form they will
      take and exactly how they can be overcome.When spouses face a divorce, they are
      intimately involved in unfamiliar territory. With the help of a qualified
      pastoral counselor and an attorney functioning as an interdisciplinary team, they
      can face divorce and post-divorce problems bravely, in an informed manner, with
      proper perspective and realistically. Each should be prepared to discuss and
      evaluate the future relationship of the parties and their children in the areas
      of future finances, credit, the second marriage, visitation, relationship to the
      children, and their insurance estates. Then there are few surprises. The new life
      can begin with an increased awareness that prepares each party for future
      contingencies. Also, the lawyer and pastoral counselor become a supportive team
      who are available both now and in the future.

PMID- 24318093
TI  - The chaplain as therapist.
AB  - In this presentation I have explored the dynamics that go on in therapy, showing
      how similar dynamics occur in pastoral relationships primarily in terms of the
      transference and countertransference phenomena. I have also called attention to
      issues or areas of concern that arise in therapy, equating them with issues with
      which theology has historically dealt, i.e., the relation of the natural to the
      supernatural, the problem of authority, the place of values in life, and the
      importance of individual responsibility. Finally, I have noted the importance of
      the chaplain's utilizing of psychodynamics in his ministry and specifically those
      areas where he should become informed and skilled, i.e., in the area of
      personality development as a way of understanding himself and in the factors that
      promote change and growth in another person. I have briefly noted the value of
      psychodynamics at the time of grief or loss.I hope that the focus upon the theme
      "the chaplain as therapist" will stimulate us to look at our ministry again. For
      those to whom this subject is new, may there be an interest in exploring it as an
      enriching dimension of ministry. For those who are already familiar with the
      impact that psychotherapy can have upon their ministry, may there be further
      experimentation at greater depth and broader latitude of some of the areas
      suggested in this treatment of the topic. 

PMID- 24318094
TI  - Effect of axillary lymph node dissection after sentinel lymph node biopsy on
      overall survival in patients with T1 or T2 node-positive breast cancer: report
      from the Korean Breast Cancer Society.
AB  - BACKGROUND: The effect of axillary lymph node dissection (ALND) after sentinel
      lymph node biopsy (SLNB) in patients with clinically node-negative patients in
      preoperative evaluations on overall survival (OS) is uncertain. The study aimed
      to evaluate the difference of survival between node-positive patients who
      underwent SLNB alone and those who received ALND after SLNB using the Korean
      Breast Cancer Society registry. METHODS: We enrolled 2,581 patients who met the
      eligibility criteria. All enrolled patients had T1 or T2 breast cancer, and
      received mastectomy or breast-conserving treatment followed by documented
      adjuvant systemic therapy. RESULTS: There were 197 patients with SLNB alone and
      2,384 patients with ALND after SLNB. Smaller tumor size, lower number of nodal
      metastasis, and higher proportion of breast-conserving surgery were found in
      patients with SLNB alone than in those with ALND after SLNB. There was no
      significant difference in OS between the two groups by the log-rank test. ALND
      after SLNB showed no significant improvement in OS in multivariate analysis.
      CONCLUSIONS: ALND in patients with sentinel metastasis who have T1 or T2 breast
      cancer receiving adjuvant systemic therapy may not have improved OS.

PMID- 24318095
TI  - Establishment of a multidisciplinary hepatocellular carcinoma clinic is
      associated with improved clinical outcome.
AB  - PURPOSE: To evaluate differences in overall survival in patients with
      hepatocellular carcinoma (HCC) after the establishment of a multidisciplinary
      clinic (MDC) for HCC. METHODS: Patient demographic and tumor characteristics of
      355 patients diagnosed with HCC were collected between October 2006 and September
      2011. Patients diagnosed after the initiation of the HCC MDC on October 1, 2010,
      were compared to patients diagnosed in the 4 years before. Patient demographics,
      tumor characteristics, treatment regimens, and overall survival were analyzed
      between the groups. RESULTS: A total of 105 patients were diagnosed in the time
      period after HCC MDC initiation compared to 250 patients in the previous 4 years.
      Patients diagnosed with HCC after the HCC MDC had fewer symptoms at presentation
      (64 vs. 78 %, p = 0.01) and earlier stage of tumor presentation [Barcelona Clinic
      for Liver Cancer (BCLC) A stage, 44 vs. 26 %, p = 0.0003; tumor, node, metastasis
      classification system stage 1, 44 vs. 30 %, p = 0.003) compared with patients
      diagnosed before MDC formation. The median time to treatment after diagnosis in
      the later period was significantly shorter than in the earlier time period (2.3
      vs. 5.3 months, p = 0.002). On multivariate analysis, being seen in the HCC MDC
      remained independently associated with better overall survival (hazard ratio 2.5,
      95 % confidence interval 2-3), after adjusting for BCLC stage and recipient of
      curative treatment. Patients diagnosed after HCC MDC initiation had a median
      survival of 13.2 months compared to the 4.8 months observed in patients diagnosed
      before MDC formation (p = 0.005). CONCLUSIONS: The implementation of a MDC for
      the evaluation and treatment of patients with HCC is associated with improved
      overall survival.

PMID- 24318096
TI  - IGF2 DMR0 methylation, loss of imprinting, and patient prognosis in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Insulin like growth factor 2 gene (IGF2) is normally imprinted. Loss
      of imprinting (LOI) of IGF2 in humans is associated with an increased risk of
      cancer and is controlled by CpG-rich regions known as differentially methylated
      regions (DMRs). Specifically, the methylation level at IGF2 DMR0 is correlated
      with IGF2 LOI and is a suggested surrogate marker for IGF2 LOI. A relationship
      between IGF2 DMR0 hypomethylation and poor prognosis has been shown in colorectal
      cancer. However, to our knowledge, no study has examined the relationships among
      the IGF2 DMR0 methylation level, LOI, and clinical outcome in esophageal squamous
      cell carcinoma (ESCC). METHODS: The IGF2 imprinting status was screened using
      ApaI polymorphism, and IGF2 protein expression was evaluated by
      immunohistochemistry with 30 ESCC tissue specimens. For survival analysis, IGF2
      DMR0 methylation was measured using a bisulfite pyrosequencing assay with 216
      ESCC tissue specimens. RESULTS: Twelve (40 %) of 30 cases were informative (i.e.,
      heterozygous for ApaI), and 5 (42 %) of 12 informative cases displayed IGF2 LOI.
      IGF2 LOI cases exhibited lower DMR0 methylation levels (mean 23 %) than IGF2 non
      LOI cases (37 %). The IGF2 DMR0 methylation level was significantly associated
      with IGF2 protein expression. Among 202 patients eligible for survival analysis,
      IGF2 DMR0 hypomethylation was significantly associated with higher cancer
      specific mortality. CONCLUSIONS: The IGF2 DMR0 methylation level in ESCC was
      associated with IGF2 LOI and IGF2 protein expression. In addition, IGF2 DMR0
      hypomethylation was associated with a shorter survival time, suggesting its
      potential role as a prognostic biomarker.

PMID- 24318097
TI  - Multidisciplinary clinic in the management of hepatocellular carcinoma.

PMID- 24318098
TI  - Liposome-mediated delivery of tobacco mosaic virus RNA into petunia protoplast :
      Improved conditions for liposome-protoplast incubations.
AB  - Liposome-mediated delivery of TMV RNA into petunia protoplasts and resulting
      virus antigen production has been used as an assay for determining incubation
      conditions which favor increased uptake of vesicle contents by plant cells.
      Vesicle phospholipid composition, incubation buffer divalent metal ion
      concentration, the type and concentration of polyalcohol used to stimulate
      vesicle uptake and the RNA content of the liposome preparation were determined to
      be critical factors influencing the efficiency of delivery. Manipulation of these
      parameters resulted in a 50-fold improvement in virus antigen production over
      that obtained with conditions previously used for liposome-protoplast incubations
      (Proc Natl Acad Sci 79: 1859-1863, 1982). Virus antigen production could be
      detected following incubation of protoplasts with <0.5 ng of encapsulated TMV
      RNA, while at higher concentrations of added liposomes, >80% of the protoplasts
      could be infected. Comparisons with other techniques used to introduce nucleic
      acids into plant protoplasts indicated that liposome-mediated delivery was 10-to
      1 000-fold more efficient than these other methods. The general use of liposomes
      to introduce RNA and DNA molecules into plant protoplasts is discussed. 

PMID- 24318099
TI  - Detection of avocado sunblotch viroid (ASBV) by dot-spot self-hybridization with
      a [(32)P]-labelled ASBV-RNA.
AB  - RNA was extracted from plants infected with avocado sunblotch viroid (ASBV) and
      was analyzed by electrophoresis in polyacrylamide gel. The ASBV related fraction
      was eluted from the gel, labelled with [(32)P] using polynucleotide kinase and
      used as a probe for hybridization with a purified ASBV-RNA preparation dot
      spotted on nitrocellulose paper. Positive self-hybridization indicated a high
      degree of internal complementarity. Dot spots of whole cell RNA and of leaf sap
      from ASBV infected plants were shown to hybridize with the labelled probe. This
      hybridization procedure proved to be 16-64 times more sensitive in diagnosing
      ASBV when compared with polyacrylamide gel analysis. 

PMID- 24318100
TI  - Flow cytometric analysis of tobacco and cowpea protoplasts infected in vivo and
      in vitro with alfalfa mosaic virus.
AB  - Immunofluorescence flow cytometry was used to study the distribution of viral
      antigen in protoplast populations. Protoplasts were isolated from healthy and
      alfalfa mosaic virus (AMV) infected tobacco leaves (designated in vivo infected).
      Furthermore isolated tobacco and cowpea protoplasts were infected in vitro with
      AMV. The FITC-conjugated antibodies could penetrate formaldehyde fixed
      protoplasts. The flow cytometric measurements were rapid and reproducible.
      Comparable immunofluorescence patterns were found for all infected samples (per
      sample 10(4) protoplasts were measured). Infectious virus could only be detected
      in in vivo infected tobacco protoplasts and in in vitro infected cowpea
      protoplasts. 

PMID- 24318101
TI  - Uncut recombinant plasmids bearing nested cauliflower mosaic virus genomes infect
      plants by intragenomic recombination.
AB  - Experiments are described which show that recombinant plasmids bearing
      cauliflower mosaic virus genomes flanked by homologous viral DNA arms ('nested'
      viral genomes) can infect plants without prior excision of the CaMV genome.
      Infectious viral genomes are excised from such recombinant plasmids within the
      plant by a process of intramolecular recombination. The frequency of infection,
      and presumably recombination increase with the length of the homologous DNA
      flanking the CaMV genome. This mechanism affords us the opportunity to transfer
      directly the CaMV genome from bacteria to plants. 

PMID- 24318102
TI  - Two-step processing of in vivo synthesized rice lectin.
AB  - The synthesis and processing of rice lectin was followed in vivo in developing
      rice embryos. Using labelling and pulse-chase labelling experiments, the sequence
      of events in the synthesis and post-translational modifications of this protein
      could be determined. The primary lectin product observed in vivo is a high
      molecular weight precursor (28 K), which is post-translationally converted to a
      23 K lectin protein, and in a further step cleaved into two smaller 12 K and 10 K
      polypeptides. The first step of the processing of the rice lectin is a rather
      slow process (the precursor has a half-life of about 3 h) and resembles the so
      called vectorial processing of cytoplasmically made organellar proteins. The
      second modification consists of a (slow) proteolytic cleavage of the basic lectin
      subunit into two smaller polypeptides and resembles somewhat the cleavage of some
      legume (storage) proteins in their protein bodies. 

PMID- 24318103
TI  - Diadenosine tetraphosphate (Ap4A): a putative chemical messenger of cell
      proliferation control and inducer of DNA replication : Review paper.

PMID- 24318104
TI  - The structure and function of plant genomes : A report.

PMID- 24318105
TI  - Independent and additive effects of atenolol and methionine restriction on
      lowering rat heart mitochondria oxidative stress.
AB  - A low rate of mitochondrial ROS production (mitROSp) and a low degree of fatty
      acid unsaturation are characteristic traits of long-lived animals and can be
      obtained in a single species by methionine restriction (MetR) or atenolol (AT)
      treatments. However, simultaneous application of both treatments has never been
      performed. In the present investigation it is shown that MetR lowers mitROSp and
      complex I content. Both the MetR and the AT treatments lower protein oxidative
      modification and oxidative damage to mtDNA and the fatty acid unsaturation degree
      in rat heart mitochondria. The decrease in fatty acid unsaturation seems to be
      due, at least in part, to decreases in desaturase and elongase activities or
      peroxisomal beta-oxidation. Furthermore, the phosphorylation of extracellular
      signal-regulated kinase (ERK) was stimulated by MetR and AT. The decrease in
      membrane fatty acid unsaturation and protein oxidation, and the changes in fatty
      acids and p-ERK showed additive effects of both treatments. In addition, the
      increase in mitROSp induced by AT observed in the present investigation was
      totally avoided with the combined MetR + AT treatment. It is concluded that the
      simultaneous treatment with MetR plus atenolol is more beneficial than either
      single treatment alone to lower oxidative stress in rat heart mitochondria,
      analogously to what has been reported in long-lived animal species. 

PMID- 24318106
TI  - Differences between arthroplasty and anterior cervical fusion in two-level
      cervical degenerative disc disease.
AB  - PURPOSE: Although arthroplasty is an accepted option for two-level disease, there
      is a paucity of data regarding outcomes of two-level cervical arthroplasty. The
      current study was designed to determine differences between two-level cervical
      arthroplasty and anterior fusion. METHODS: Seventy-seven consecutive patients who
      underwent two-level anterior cervical operations for degenerative disc disease
      were divided into the arthroplasty (37 patients) and fusion (40 patients) groups.
      Clinical outcomes were measured by Visual Analogue Scale (VAS) of neck and arm
      pain, Japanese Orthopedic Association (JOA) scores, and Neck Disability Index
      (NDI). Every patient was evaluated by radiography and computed tomography for
      fusion or detection of heterotopic ossification. RESULTS: Thirty-seven patients
      (with 74 levels of Bryan discs) were compared with 40 patients who had two-level
      anterior fusion (mean follow-up of 39.6 +/- 6.7 months). There was no difference
      in sex, but the mean age of the arthroplasty group was significantly younger
      (52.1 +/- 9.1 vs. 63.0 +/- 10.6 years, p < 0.001). The mean estimated blood loss
      was similar (p = 0.135), but the mean operation time was longer in the
      arthroplasty group (315.5 +/- 82.0 versus 224.9 +/- 61.8 min, p < 0.001). At 24
      months post-operation, the arthroplasty group had increased their range of motion
      than pre-operation (23.5 degrees  versus 20.1 degrees , p = 0.018). There were
      significant improvements in neck or arm VAS, JOA scores, and NDI in both groups.
      However, there were no differences in clinical outcomes or adverse events between
      the two groups. CONCLUSIONS: Clinical outcomes of two-level arthroplasty and
      anterior cervical fusion are similar 39.6 months after surgery. Cervical
      arthroplasty preserves mobility at the index levels without increased adverse
      effects.

PMID- 24318107
TI  - Characterization of EstB, a novel cold-active and organic solvent-tolerant
      esterase from marine microorganism Alcanivorax dieselolei B-5(T).
AB  - A novel esterase gene, estB, was cloned from the marine microorganism Alcanivorax
      dieselolei B-5(T) and overexpressed in E. coli DE3 (BL21). The expressed protein
      EstB with a predicted molecular weight of 45.1 kDa had a distinct catalytic triad
      (Ser(211)-Trp(353)-Gln(385)) and the classical consensus motif conserved in most
      lipases and esterases Gly(209)-X-Ser(211)-X-Gly(213). EstB showed very low
      similarity to any known proteins and displayed the highest similarity to the
      hypothetical protein (46%) from Rhodococcus jostii RHA1. EstB showed the optimal
      activity around pH 8.5 and 20  degrees C and was identified to be extremely cold
      adaptative retaining more than 95% activity between 0 and 10  degrees C. The
      values of kinetic parameters on p-NP caproate (K m, K cat and K cat/K m) were
      0.15 mM, 0.54 * 10(3) s(-1) and 3.6 * 10(3) s(-1) mM(-1), respectively. In
      addition, EstB showed remarkable stability in several studied organic solvents
      and detergents of high concentrations with the retention of more than 70%
      activity after treatment for 30 min. The cold activity and its tolerance towards
      organic solvents made it a promising biocatalyst for industrial applications
      under extreme conditions.

PMID- 24318108
TI  - Isolation, growth and genome of the Rhodothermus RM378 thermophilic
      bacteriophage.
AB  - Several bacteriophages that infect different strains of the thermophilic
      bacterium Rhodothermus marinus were isolated and their infection pattern was
      studied. One phage, named RM378 was cultivated and characterized. The RM378
      genome was also sequenced and analyzed. The phage was grouped as a member of the
      Myoviridae family with A2 morphology. It had a moderately elongated head, with
      dimensions of 85 and 95 nm between opposite apices and a 150 nm long tail,
      attached with a connector to the head. RM378 showed a virulent behavior that
      followed a lytic cycle of infection. It routinely gave lysates with 10(11)
      pfu/ml, and sometimes reached titers as high as 10(13) pfu/ml. The titer remained
      stable up to 65  degrees C but the phage lost viability when incubated at higher
      temperatures. Heating for 30 min at 96  degrees C lowered the titer by 10(4). The
      RM378 genome consisted of ds DNA of 129.908 bp with a GC ratio of 42.0% and
      contained about 120 ORFs. A few structural proteins, such as the major head
      protein corresponding to the gp23 in T4, could be identified. Only 29 gene
      products as probable homologs to other proteins of known function could be
      predicted, with most showing only low similarity to known proteins in other
      bacteriophages. These and other studies based on sequence analysis of a large
      number of phage genomes showed RM378 to be distantly related to all other known
      T4-like phages.

PMID- 24318109
TI  - A novel cold-active and salt-tolerant alpha-amylase from marine bacterium
      Zunongwangia profunda: molecular cloning, heterologous expression and biochemical
      characterization.
AB  - A novel gene (amyZ) encoding a cold-active and salt-tolerant alpha-amylase (AmyZ)
      was cloned from marine bacterium Zunongwangia profunda (MCCC 1A01486) and the
      protein was expressed in Escherichia coli. The gene has a length of 1785 bp and
      encodes an alpha-amylase of 594 amino acids with an estimated molecular mass of
      66 kDa by SDS-PAGE. The enzyme belongs to glycoside hydrolase family 13 and shows
      the highest identity (25%) to the characterized alpha-amylase TVA II from
      thermoactinomyces vulgaris R-47. The recombinant alpha-amylase showed the maximum
      activity at 35  degrees C and pH 7.0, and retained about 39% activity at 0 
      degrees C. AmyZ displayed extreme salt tolerance, with the highest activity at
      1.5 M NaCl and 93% activity even at 4 M NaCl. The catalytic efficiency (k cat/K
      m) of AmyZ increased from 115.51 (with 0 M NaCl) to 143.30 ml mg(-1) s(-1) (with
      1.5 M NaCl) at 35  degrees C and pH 7.0, using soluble starch as substrate.
      Besides, the thermostability of the enzyme was significantly improved in the
      presence of 1.5 M NaCl or 1 mM CaCl2. AmyZ is one of the very few alpha-amylases
      that tolerate both high salinity and low temperatures, making it a potential
      candidate for research in basic and applied biology.

PMID- 24318110
TI  - PEDF expression regulates the proangiogenic and proinflammatory phenotype of the
      lung endothelium.
AB  - Pigment epithelium-derived factor (PEDF) is a multifunctional protein with
      important roles in regulation of inflammation and angiogenesis. It is produced by
      various cell types, including endothelial cells (EC). However, the cell
      autonomous impact of PEDF on EC function needs further investigation. Lung EC
      prepared from PEDF-deficient (PEDF-/-) mice were more migratory and failed to
      undergo capillary morphogenesis in Matrigel compared with wild type (PEDF+/+) EC.
      Although no significant differences were observed in the rates of apoptosis in
      PEDF-/- EC compared with PEDF+/+ cells under basal or stress conditions, PEDF-/-
      EC proliferated at a slower rate. PEDF-/- EC also expressed increased levels of
      proinflammatory markers, including vascular endothelial growth factor, inducible
      nitric oxide synthase, vascular cell adhesion molecule-1, as well as altered
      cellular junctional organization, and nuclear localization of beta-catenin. The
      PEDF-/- EC were also more adhesive, expressed decreased levels of thrombospondin
      2, tenascin-C, and osteopontin, and increased fibronectin. Furthermore, we showed
      lungs from PEDF-/- mice exhibited increased expression of macrophage marker
      F4/80, along with increased thickness of the vascular walls, consistent with a
      proinflammatory phenotype. Together, our data suggest that the PEDF expression
      makes significant contribution to modulation of the inflammatory and angiogenic
      phenotype of the lung endothelium. 

PMID- 24318112
TI  - Fluctuation of cilia-generated flow on the surface of the tracheal lumen.
AB  - Although we inhale air that contains many harmful substances, including, for
      example, dust and viruses, these small particles are trapped on the surface of
      the tracheal lumen and transported towards the larynx by cilia-generated flow.
      The transport phenomena are affected not only by the time- and space-average flow
      field but also by the fluctuation of the flow. Because flow fluctuation has
      received little attention, we investigated it experimentally in mice. To
      understand the origin of flow fluctuation, we first measured the distribution of
      ciliated cells in the trachea and individual ciliary motions. We then measured
      the detailed flow field using a confocal micro-PTV system. Strong flow
      fluctuations were observed, caused by the unsteadiness of the ciliary beat and
      the spatial inhomogeneity of ciliated cells. The spreading of particles relative
      to the bulk motion became diffusive if the time scale was sufficiently larger
      than the beat period. Finally, we quantified the effects of flow fluctuation on
      bulk flow by evaluating the Peclet number of the system, which indicated that the
      directional transport was an order of magnitude larger than the isotropic
      diffusion. These results are important in understanding transport phenomena in
      the airways on a cellular scale. 

PMID- 24318111
TI  - HIV envelope protein gp120-induced apoptosis in lung microvascular endothelial
      cells by concerted upregulation of EMAP II and its receptor, CXCR3.
AB  - Chronic lung diseases, such as pulmonary emphysema, are increasingly recognized
      complications of infection with the human immunodeficiency virus (HIV). Emphysema
      in HIV may occur independent of cigarette smoking, via mechanisms that are poorly
      understood but may involve lung endothelial cell apoptosis induced by the HIV
      envelope protein gp120. Recently, we have demonstrated that lung endothelial
      apoptosis is an important contributor to the development of experimental
      emphysema, via upregulation of the proinflammatory cytokine endothelial monocyte
      activating polypeptide II (EMAP II) in the lung. Here we investigated the role of
      EMAP II and its receptor, CXCR3, in gp120-induced lung endothelial cell
      apoptosis. We could demonstrate that gp120 induces a rapid and robust increase in
      cell surface expression of EMAP II and its receptor CXCR3. This surface
      expression occurred via a mechanism involving gp120 signaling through its CXCR4
      receptor and p38 MAPK activation. Both EMAP II and CXCR3 were essentially
      required for gp120-induced apoptosis and exposures to low gp120 concentrations
      enhanced the susceptibility of endothelial cells to undergo apoptosis when
      exposed to soluble cigarette smoke extract. These data indicate a novel mechanism
      by which HIV infection causes endothelial cell loss involved in lung emphysema
      formation, independent but potentially synergistic with smoking, and suggest
      therapeutic targets for emphysema prevention and/or treatment. 

PMID- 24318113
TI  - Influence of glucocorticoids, neuregulin-1beta, and sex on surfactant
      phospholipid secretion from type II cells.
AB  - Glucocorticoids induce lung fibroblasts to produce fibroblast-pneumocyte factor,
      a peptide that stimulates type II cells to synthesize pulmonary surfactant. This
      effect is known to be more apparent in cells derived from female fetuses, a
      characteristic that has been attributed to sex-linked differences in the
      fibroblasts. In the current study, it has been shown that dexamethasone enhances
      both beta-adrenergic receptor (beta-AR) activity (1.3- to 1.6-fold increase) and
      (-)-isoproterenol-induced secretion of surfactant (1.8- to 1.9-fold increase) in
      type II cells. However, fibroblast-conditioned media (FCM), prepared in the
      presence of dexamethasone, generates a much greater response to (-)-isoproterenol
      (3.1- to 3.8-fold increase). Furthermore, each of these effects is more
      pronounced if both cell types are female-derived. It is hypothesized that the
      enhanced response to glucocorticoids is the result of a synergistic effect
      between the steroid and a component of FCM. Neuregulin-1beta (NRG1beta), which is
      elevated in FCM generated in the presence of dexamethasone, influences not only
      the rate of surfactant secretion and the beta-AR activity in type II cells, but
      also enhances in both sexes the cellular response to (-)-isoproterenol. These
      results suggest that NRG1beta might be more effective than glucocorticoids in
      treating prematurely born male infants, which are known to respond poorly to
      glucocorticoids. Given that glucocorticoids are known to induce higher levels of
      beta-AR mRNA, the effect of NRG1beta, alone and in combination with
      dexamethasone, on beta-AR gene expression was measured using qRT-PCR. Whereas
      NRG1beta had no effect alone, in combination with dexamethasone it produced up to
      a 4.2-fold elevation in the level of beta-AR mRNA. 

PMID- 24318114
TI  - NOX2 in lung inflammation: quantum dot based in situ imaging of NOX2-mediated
      expression of vascular cell adhesion molecule-1.
AB  - Quantum dot (QD) imaging is a powerful tool for studying signaling pathways as
      they occur. Here we employ this tool to study adhesion molecule expression with
      lung inflammation in vivo. A key event in pulmonary inflammation is the
      regulation of vascular endothelial cell adhesion molecule-1 (VCAM), which drives
      activated immune cell adherence. The induction of VCAM expression is known to be
      associated with reactive oxygen species (ROS) production, but the exact mechanism
      or the cellular source of ROS that regulates VCAM in inflamed lungs is not known.
      NADPH oxidase 2 (NOX2) has been reported to be a major source of ROS with
      pulmonary inflammation. NOX2 is expressed by both endothelial and immune cells.
      Here we use VCAM-targeted QDs in a mouse model to show that NOX2, specifically
      endothelial NOX2, induces VCAM expression with lung inflammation in vivo. 

PMID- 24318115
TI  - Aqueous cigarette smoke extract induces a voltage-dependent inhibition of CFTR
      expressed in Xenopus oocytes.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel
      inhabits the apical membrane of airway epithelia, where its function is essential
      for mucus hydration, mucociliary clearance, and airway defense. Chronic
      obstructive pulmonary disease (COPD), most often a consequence of cigarette smoke
      (CS) exposure, affects 15 million persons in the US. Clinically, COPD is
      characterized by many of the salient features of cystic fibrosis lung disease,
      where CFTR is either absent or reduced in function. CS is an acidic aerosol (pH
      5.3 to 6.3) reported to contain over 4,000 constituents. Acute CS exposure has
      been reported to decrease airway transepithelial voltage in vivo and short
      circuit current in vitro; however, the mechanistic basis of these effects is
      uncertain. The goal of the studies described here was to develop a bioassay to
      characterize the effects of aqueous CS preparations on the channel function of
      CFTR. We studied aqueous CS extract (CSE) prepared in our laboratory, as well as
      commercial cigarette smoke condensate (CSC) in Xenopus oocytes expressing human
      CFTR. Application of CSE at pH 5.3 produced a reversible, voltage-dependent
      inhibition of CFTR conductance. CSE neutralized to pH 7.3 produced less
      inhibition of CFTR conductance. Serial dilution of CSE revealed a dose-dependent
      effect at acidic and neutral pH. In contrast, CSC did not inhibit CFTR
      conductance in oocytes. We conclude that one or more components of CSE inhibits
      CFTR in a manner similar to diphenylamine-2-carboxylate, a negatively charged,
      open-channel blocker. 

PMID- 24318123
TI  - Cancer incidence and mortality following exposures to distal and proximal major
      stressors.
AB  - PURPOSE: Severe psychological trauma has been shown to leave psychological and
      biological sequelae, including compromise of the neuro-hormonal and immunological
      systems. Despite much research, the putative effect of such stressor on cancer
      remains ambiguous. This study maximized the exploration of cancer incidence and
      mortality by combining a proximal (parental bereavement) with a distal major
      stressor (Holocaust exposure) on both risks. METHODS: Subjects were bereaved
      Holocaust survivors (n = 904) and comparison individuals (n = 933) selected from
      the total cohort of 6,284 Jewish-Israeli parents who lost an adult son in war or
      from non-self-inflicted external causes. Cox regression was used to examine the
      differential risk for cancer between the two bereaved samples, adjusting for
      potential confounders. RESULTS: No difference in cancer incidence or mortality
      was observed between both groups of bereaved parents. However, prior to
      bereavement, Holocaust survivors had an increased cancer risk compared with their
      counterparts in the general population. CONCLUSIONS: Individuals who faced both a
      proximal (bereavement) and distal (Holocaust) major stressors had no additive
      risk for cancer incidence and mortality.

PMID- 24318116
TI  - The mercurial nature of neutrophils: still an enigma in ARDS?
AB  - The acute respiratory distress syndrome (ARDS) is a life-threatening lung
      condition resulting from direct and indirect insults to the lung. It is
      characterized by disruption of the endothelial-epithelial barrier, alveolar
      damage, pulmonary edema, and respiratory failure. A key feature of ARDS is the
      accumulation of neutrophils in the lung microvasculature, interstitium, and
      alveolar space. Despite a clear association between neutrophil influx into the
      lung and disease severity, there is some debate as to whether neutrophils
      directly contribute to disease pathogenesis. The primary function of neutrophils
      is to provide immediate host defense against pathogenic microorganisms.
      Neutrophils release numerous antimicrobial factors such as reactive oxygen
      species, proteinases, and neutrophil extracellular traps. However, these factors
      are also toxic to host cells and can result in bystander tissue damage. The
      excessive accumulation of neutrophils in ARDS may therefore contribute to disease
      progression. Central to neutrophil recruitment is the release of chemokines,
      including the archetypal neutrophil chemoattractant IL-8, from resident pulmonary
      cells. However, the chemokine network in the inflamed lung is complex and may
      involve several other chemokines, including CXCL10, CCL2, and CCL7. This review
      will therefore focus on the experimental and clinical evidence supporting
      neutrophils as key players in ARDS and the chemokines involved in recruiting them
      into the lung. 

PMID- 24318126
TI  - Three-dimensional imaging and navigated sentinel node biopsy for primary parotid
      malignancy: new application in parotid cancer management.
AB  - BACKGROUND: Applications for sentinel node biopsy (SNB) in the head and neck are
      increasing with new lymphatic tracers and imaging techniques allowing previously
      inaccessible tumor sites to benefit from the procedure. We show that lymphatic
      drainage from a primary parotid malignancy can be accurately mapped using
      navigational surgery. METHODS: A patient with radiologically classified N0
      intraparotid malignancy underwent peritumoral injection of 99mTc-nanocolloid.
      Planar imaging and single photon emission CT (SPECT)/CT identified the sentinel
      node. At surgery, real-time video combined with 3 dimensional (3D) images of
      intraoperative radioisotope hot spots directed the surgeon to the sentinel node.
      RESULTS: Lymphoscintographic images demonstrated the hot nodes, which were easily
      retrieved intraoperatively by 3D navigation. Three lymph nodes were removed, all
      were free of metastasis. CONCLUSION: The morbidity associated with total
      parotidectomy and elective neck dissection in low-risk malignancies may be
      avoided with SNB. This technique is applicable to other sites within the head and
      neck.

PMID- 24318125
TI  - Color and illuminance level of lighting can modulate willingness to eat bell
      peppers.
AB  - BACKGROUND: Food products are often encountered under colored lighting,
      particularly in restaurants and retail stores. However, relatively little
      attention has been paid to whether the color of ambient lighting can affect
      consumers' motivation for consumption. This study aimed to determine whether
      color (Experiment 1) and illuminance level (Experiment 2) of lighting can
      influence consumers' liking of appearance and their willingness to eat bell
      peppers. RESULTS: For red, green, and yellow bell peppers, yellow and blue
      lighting conditions consistently increased participants' liking of appearance the
      most and the least, respectively. Participants' willingness to consume bell
      peppers increased the most under yellow lighting and the least under blue
      lighting. In addition, a dark condition (i.e. low level of lighting illuminance)
      decreased liking of appearance and willingness to eat the bell peppers compared
      to a bright condition (i.e. high level of lighting illuminance). CONCLUSION: Our
      findings demonstrate that lighting color and illuminance level can influence
      consumers' hedonic impression and likelihood to consume bell peppers.
      Furthermore, the influences of color and illuminance level of lighting appear to
      be dependent on the surface color of bell peppers.

PMID- 24318127
TI  - Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica.
AB  - Neuromyelitis optica is a rare neurological autoimmune disorder characterized by
      a poor prognosis. Immunosuppression can halt disease progression, but some
      patients are refractory to multiple treatments, experiencing frequent relapses
      with accumulating disability. Here we report on durable clinical remissions after
      allogeneic hematopoietic stem cell transplantation in 2 patients suffering from
      severe forms of the disease. Immunological data evidenced disappearance of the
      pathogenic antibodies and regeneration of a naive immune system of donor origin.
      These findings correlated with evident clinical and radiological improvement in
      both patients, warranting extended clinical trials to investigate this promising
      therapeutic option.

PMID- 24318129
TI  - Forever?

PMID- 24318130
TI  - Is religion therapeutically significant?

PMID- 24318131
TI  - The psychology of grief and mourning in Judaism.

PMID- 24318124
TI  - Neuropathology of stress.
AB  - Environmental challenges are part of daily life for any individual. In fact,
      stress appears to be increasingly present in our modern, and demanding,
      industrialized society. Virtually every aspect of our body and brain can be
      influenced by stress and although its effects are partly mediated by powerful
      corticosteroid hormones that target the nervous system, relatively little is
      known about when, and how, the effects of stress shift from being beneficial and
      protective to becoming deleterious. Decades of stress research have provided
      valuable insights into whether stress can directly induce dysfunction and/or
      pathological alterations, which elements of stress exposure are responsible, and
      which structural substrates are involved. Using a broad definition of pathology,
      we here review the "neuropathology of stress" and focus on structural
      consequences of stress exposure for different regions of the rodent, primate and
      human brain. We discuss cytoarchitectural, neuropathological and structural
      plasticity measures as well as more recent neuroimaging techniques that allow
      direct monitoring of the spatiotemporal effects of stress and the role of
      different CNS structures in the regulation of the hypothalamic-pituitary-adrenal
      axis in human brain. We focus on the hypothalamus, hippocampus, amygdala, nucleus
      accumbens, prefrontal and orbitofrontal cortex, key brain regions that not only
      modulate emotions and cognition but also the response to stress itself, and
      discuss disorders like depression, post-traumatic stress disorder, Cushing
      syndrome and dementia. 

PMID- 24318128
TI  - SCF beta-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate
      cancer cell proliferation and migration.
AB  - Metastasis suppressor 1 (MTSS1) is an important tumor suppressor protein, and
      loss of MTSS1 expression has been observed in several types of human cancers.
      Importantly, decreased MTSS1 expression is associated with more aggressive forms
      of breast and prostate cancers, and with poor survival rate. Currently, it
      remains unclear how MTSS1 is regulated in cancer cells, and whether reduced MTSS1
      expression contributes to elevated cancer cell proliferation and migration. Here
      we report that the SCFbeta-TRCP regulates MTSS1 protein stability by targeting it
      for ubiquitination and subsequent destruction via the 26S proteasome. Notably,
      depletion of either Cullin 1 or beta-TRCP1 led to increased levels of MTSS1. We
      further demonstrated a crucial role for Ser322 in the DSGXXS degron of MTSS1 in
      governing SCFbeta-TRCP-mediated MTSS1 degradation. Mechanistically, we defined
      that Casein Kinase Idelta (CKIdelta) phosphorylates Ser322 to trigger MTSS1's
      interaction with beta-TRCP for subsequent ubiquitination and degradation.
      Importantly, introducing wild-type MTSS1 or a non-degradable MTSS1 (S322A) into
      breast or prostate cancer cells with low MTSS1 expression significantly inhibited
      cellular proliferation and migration. Moreover, S322A-MTSS1 exhibited stronger
      effects in inhibiting cell proliferation and migration when compared to ectopic
      expression of wild-type MTSS1. Therefore, our study provides a novel molecular
      mechanism for the negative regulation of MTSS1 by beta-TRCP in cancer cells. It
      further suggests that preventing MTSS1 degradation could be a possible novel
      strategy for clinical treatment of more aggressive breast and prostate cancers.

PMID- 24318132
TI  - A child and adam: A parable of the two ages.

PMID- 24318133
TI  - Three levels of mate selection and marital interaction.

PMID- 24318134
TI  - Clinical-counseling supervision and community mental health.

PMID- 24318135
TI  - "What will happen to the flowers when winter comes?".

PMID- 24318136
TI  - Self-fulfillment, asceticism, and the function of authority.

PMID- 24318137
TI  - Characterization of the rDNA repeat units in the MitchellPetunia genome.
AB  - The principal rDNA repeating unit in the MitchellPetunia genome has a length of
      8.5 kb. In addition there is a major variant of length 9.7 kb, and two minor
      variants of 9.3 kb and 10.4 kb. The size heterogeneity of the rDNA repeating
      units results from length differences in the non-transcribed spacer regions.
      These differences may reflect simple insertions into the non-transcribed spacer
      region of the major 'short' repeat; however, additional sequence changes have
      occurred since the 'short' repeat is characterized by restriction endonuclease
      cleavage sites which are absent in the longer variant units. 

PMID- 24318138
TI  - Chloroplast RNA polymerase from spinach: purification and DNA-binding proteins.
AB  - Spinach DNA dependent RNA polymerase was purified from isolated chloroplasts by
      two different procedures. Analysis of the protein composition of the two
      preparations by SDS-polyacrylamide gel electrophoresis always shows six abundant
      polypeptides with Mr of 150, 110, 102, 80, 75 and 38 Kd and one less abundant
      polypeptide of 25 Kd. Some other proteins ranging from 40-70 Kd in Mr are also
      detected but in a minor and variable amount. The two preparations have an optimum
      of enzyme activity at 30 degrees C and at 15 mM (NH4)2SO4 when tested with
      denatured calf thymus DNA.Binding experiments with two different nick translated
      fragments of spinach chloroplast DNA show that the 80 and 75 Kd polypeptides
      possess a strong DNA binding capacity. 

PMID- 24318139
TI  - Improved yield of full-length phaseolin cDNA clones by controlling premature
      anticomplementary DNA synthesis.
AB  - The manner in which the known enzymatic properties of reverse transcriptase may
      limit the length of double stranded cDNAs to be used in cloning was studied.
      Results here suggest that the well-documented ability of reverse transcriptase to
      synthesize anticomplementary DNA can, if unrecognized, seriously limit the final
      yield of full-length cDNA clones. Under conditions which permitted
      anticomplementary DNA synthesis during the synthesis of the first cDNA strand, no
      full-length cDNA clones for phaseolin, the principal storage proteins ofPhaseolus
      vulgaris, were detected among 19 phaseolin-positive cDNA clones. When
      anticomplementary DNA synthesis was inhibited with 4 mM sodium pyrophosphate, 5
      full-length cDNA clones were identified among 45 phaseolin-positive clones. In
      both cases, the products of the first strand synthesis were C-tailed and the
      second strand synthesized by reverse transcriptase using oligo(dG) as a primer.
      The implications of anticomplementary synthesis in cloning methods involving the
      use of S1 nuclease are discussed. In addition, a rapid, one-step procedure for
      obtaining partial clones which equally represent the 5' and 3' ends of the RNA is
      presented. 

PMID- 24318140
TI  - An alfalfa mosaic virus RNA 2 mutant, which does not induce a hypersensitive
      reaction in cowpea plants, is multiplied to a high concentration in cowpea
      protoplasts.
AB  - A mutant of alfalfa mosaic virus (AMV), which in contrast to wild type (wt) can
      invade cowpea plants systemically, is replicated more efficiently in cowpea
      protoplasts than the wt. Mutant preparations isolated from infected cowpea
      protoplasts contained a higher amount of middle component (M, containing RNA 2)
      than wt preparations. Both in cowpea plants and in cowpea protoplasts a wt
      phenotype is obtained upon addition of wt M to this mutant, suggesting a
      correlation between the type of plant reaction evoked by the virus infection and
      the regulation of viral RNA synthesis. 

PMID- 24318141
TI  - Age dependence of cowpea protoplasts for uptake of spermidine and infectibility
      by alfalfa mosaic virus.
AB  - Cowpea protoplasts were prepared from plants of different ages and examined for
      their ability to take up polyamines and for their infectibility by alfalfa mosaic
      virus. A lag period of ~20 h was necessary before the onset of rapid polyamine
      uptake; the occurrence of this rapid uptake depended on the age of the leaves
      used for protoplast preparation. The percentage of infection of cowpea
      protoplasts by alfalfa mosaic virus, and the amount of virus produced also
      depended on the age of the plants used for protoplast preparation. In contrast,
      the uptake of amino acids was rapid in all cowpea protoplasts tested. 

PMID- 24318142
TI  - Genes and transcripts for the P700 chlorophylla apoprotein and subunit 2 of the
      photosystem I reaction center complex from spinach thylakoid membranes.
AB  - A photosystem I reaction center complex has been purified to homogeneity by a
      procedure involving partial solubilization of spinach thylakoid membranes, ion
      exchange chromatography and centrifugation in sucrose gradients. The complex
      contains 7 polypeptides: the P700 chlorophylla apoprotein with an apparent
      molecular weight of 67 kd, which at high resolution splits into two bands, and
      smaller polypeptides of 22 (subunit 2), 18.5, 18, 16, 12 and 10 kd.Stable
      transcripts for the P700 chlorophylla apojprotein and subunit 2 were found in
      plastid and cytosolic RNA, respectively. The apoprotein product obtained by
      translation in a mRNA-dependent cell-free rabbit reticulocyte lysate and also by
      DNA-programmed transcription-translation of cloned plastid DNA fragments inE.
      coli lysates was indistinguishable immunologically and electrophoretically from
      the authentic protein. However, the product immunologically related to subunit 2
      was 4 kd larger than the mature compound indicating that this protein is encoded
      in the nucleus and synthesized as a precursor.The gene for the P700 chlorophylla
      apoprotein has been physically mapped on the spinach plastid chromosome by hybrid
      selection mapping and DNA-programmed cell-free transcription-translation using
      cloned restriction fragments of plastid DNA. There is one gene copy per
      chromosome and it is located centrally in the large single-copy region of the
      circular DNA molecule. This gene is uninterrupted and is transcribed in the same
      direction as that of the large subunit of ribulose bisphosphate
      carboxylase/oxygenase. Its transcript is approximately 4 kb longer than the 2 kbp
      structural gene. 

PMID- 24318143
TI  - [TMN classification of hypopharynx carcinoma - hypopharynx carcinoma: TNM
      classification].

PMID- 24318144
TI  - [Pacemaker patients in MRI: the small print by the manufacturer must be read
      (interview by Florian Schneider)].

PMID- 24318145
TI  - ["The physician who is qualified and participates in certification, improves his
      career chances" (interview by Florian Schneider)].

PMID- 24318147
TI  - [Radiology and the law - consensus on delegation of physician responsibilities
      according to 24 BMV-A - effects on radiology].

PMID- 24318149
TI  - Relationships between personal control, moral reasoning, and socioeconomic status
      of Nigerian hausa adolescents.
AB  - The Internal-External Locus of Control (I-E) Scale devised by Rotter, the revised
      Kohlberg's Scale of Moral Judgment, and a socioeconomic background questionnaire
      were administered to 97 Nigerian Hausa secondary school adolescents. Data were
      analyzed to find sex differences in locus of control and moral reasoning, and
      relationships between locus of control, moral judgment level, and socioeconomic
      status. Significant sex differences were not revealed in either locus of control
      or moral reasoning. No significant relationships between locus of control, moral
      judgment, and socioeconomic background were found. 

PMID- 24318150
TI  - The structure of values among college students: An examination of sex
      differences.
AB  - Male and female college students stated how proud or ashamed they would be of 96
      behaviors. The ratings by each sex were then factor analyzed. While personal
      accomplishments was found to be the primary factor for males, academic failure
      was the primary factor for females. An interpretation of these differences in
      terms of the operation of fear-of-failure dynamics among college women was
      suggested. Further examination of the factor structures revealed a larger number
      of morality-related factors for females than for males, suggesting that morality
      is more differentiated for females. The compatibility of this finding with
      previous research in the area of moral development was noted. 

PMID- 24318151
TI  - Health habits and depression in adolescence.
AB  - In a study of the relationship between health habits and depression, 80 high
      school students, selected on an availability basis, were administered a Health
      Behaviors Questionnaire (HBQ) and the Beck Depression Inventory (BDI). The HBQ
      and the BDI significantly correlated (r=0.43p<0.01). Those who smoked were more
      frequently depressed than those who did not (X (2)=10.5p<0.05), and those who
      used drugs other than marijuana were depressed more frequently than those who did
      not (X (2)=9.2p<0.01). Mildly overweight boys (overweight by more than 5% of
      their ideal weight) and mildly under-weight boys (underweight by more than 5% of
      their ideal weight) were more. 

PMID- 24318152
TI  - The relationship of sex role to physical and psychological health.
AB  - This study examined the relationship of sex-role typology, medical and
      psychiatric symptomatology, and personality functioning in adolescents. Seventy
      nine males and 101 females with an average age of 18.3 were administered the Bem
      Sex Role Inventory (BSRI), Offer Self Image Questionnaire (OSIQ), Self Rating
      Depression Scale (SRDS), and Cornell Medical Index (CMI). In comparison to males,
      females reported significantly more medical and psychiatric symptomatology,
      including depression. Females were also found to have more concern and empathy
      for others and a better developed superego. They reported greater involvement in
      making future plans and were more conservative in their sexual attitudes. Sex
      role typology yielded no significant differences on the medical and psychiatric
      scales, but consistent differences were found on the OSIQ, a measure of
      adolescent personality functioning. In general, the results indicated that
      androgynous teenagers in every case differed from the undifferentiated ones, with
      the masculine and feminine groups occupying a mid-position. Androgynous
      individuals always showed a more favorable adjustment. Undifferentiated
      individuals had a poorer defensive structure, less adequate coping mechanisms and
      affective integration, more confusion about body boundaries, and more difficulty
      in object relations. Androgynous individuals, in short, possessed adaptive
      capabilities and resources, such as effective coping techniques, emotional
      integration, communication skills, and a well-defined self-concept (i.e., ego
      strength and a high level of psychological integration). Since these results were
      obtained on a measure constructed solely to assess adolescent functioning, it
      seems possible to screen and identify adolescents who may be entering adulthood
      lacking the emotional, social, and occupational capacity to function in an
      optimal fashion. 

PMID- 24318153
TI  - Adolescent identification and academic achievement: Reporting the awareness of
      similarity to role models.
AB  - Individualized identification grids were administered to 16-18-year-old males
      (N=49) in order to chart the complex of identification they have established with
      their parents, peers, and school personnel. It was hypothesized that patterns of
      identification with particular acquaintances would vary as a function of
      individuals' level of academic achievement. The results of this study indicated
      that high achievers identified more often with their liked school personnel than
      did low achievers, and more often with their peers and school personnel than with
      their parents. Low achievers were shown to most often identify with their mothers
      and peer. Arguments for viewing identification as a cognitive process based upon
      reciprocal interpersonal involvement and mediated by situation-specific
      competence are presented. 

PMID- 24318154
TI  - Work and growth: A review of research on the impact of work experience on
      adolescent development.
AB  - Work has not been extensively studied as a context for adolescent development,
      even though increased work experience has been widely recommended as a means of
      improving the transition of adolescents to adulthood. Studies of the impact of
      work experience on adolescent socialization, defined broadly, suggest that work
      has beneficial results that persist over time. Developmental theorists and
      critics of conventional patterns of workplace organization remind us, however,
      that current knowledge is inadequate to specify optimal types and amounts of work
      experience for adolescents. Studies of narrower outcomes of work experience -
      career knowledge and plans, job-related attitudes, behavior, and skills - are
      less persuasive. An ecological strategy is recommended for future research. Such
      research should consider the varying effects of different kinds of work
      experience on different adolescents and should seek those effects in settings
      other than the workplace and over long periods. 

PMID- 24318155
TI  - Representation of the female body by early and late adolescent girls.
AB  - A group of 153 sixth-, seventh-, and eighth-grade girls and a group of 95 college
      women produced human figure drawings. Comparisons were made between early and
      late adolescents and, within the group of early adolescents, between pre- and
      postmenarcheal girls, of the frequency with which secondary sexual
      characteristics, namely, breasts, were explicitly depicted on the female figures.
      Early adolescents were found to represent breasts more explicitly than late
      adolescents. Parallel results were found for pre- and postmenarcheal girls in the
      seventh grade. The results suggest that early adolescents emphasize and are
      preoccupied with body parts whose changes signal the beginning of puberty, while
      later adolescents, being past the period of most rapid growth and change in body
      contour, have a more integrated body image. 

PMID- 24318156
TI  - Evaluations of self and parent figures by children from intact, divorced, and
      reconstituted families.
AB  - A total of 738 children in grades 5-8 from 14 school districts in Kansas
      voluntarily evaluated themselves, their mothers, and their fathers. The results
      of this study indicated that children from intact families tended to evaluate
      themselves and their parents more positively than those from divorced families.
      Children from remarried families, as opposed to children from nonremarried
      families, were found to evaluate themselves somewhat more positively, their
      fathers significantly more positively, and their mothers less favorably.
      Explanations are offered to account for these findings. 

PMID- 24318157
TI  - School crime and disruption as a function of student-school fit: An empirical
      assessment.
AB  - A theoretical model is described which conceptualizes school crime and disruption
      as a function of the congruence or fit between the personal characteristics of
      students and the social environments of the schools they attend. In a direct
      empirical test of the model, indices representing 10 distinct dimensions of
      student-school fit are related to three composite measures of school misconduct:
      school crime, school avoidance, and class misbehavior. A number of significant
      relationships are found between dimensions of student-school fit and the three
      indices of school misbehavior, several of which manifest one of the nonlinear
      forms specified by the model, providing at least modest support for a person
      environment fit theory of school crime and disruption. 

PMID- 24318158
TI  - SPECT/CT workflow and imaging protocols.
AB  - PURPOSE: Introducing a hybrid imaging method such as single photon emission
      computed tomography (SPECT)/CT greatly alters the routine in the nuclear medicine
      department. It requires designing new workflow processes and the revision of
      original scheduling process and imaging protocols. In addition, the imaging
      protocol should be adapted for each individual patient, so that performing CT is
      fully justified and the CT procedure is fully tailored to address the clinical
      issue. Such refinements often occur before the procedure is started but may be
      required at some intermediate stage of the procedure. Furthermore, SPECT/CT leads
      in many instances to a new partnership with the radiology department. This
      article presents practical advice and highlights the key clinical elements which
      need to be considered to help understand the workflow process of SPECT/CT and
      optimise imaging protocols. METHODS: The workflow process using SPECT/CT is
      complex in particular because of its bimodal character, the large spectrum of
      stakeholders, the multiplicity of their activities at various time points and the
      need for real-time decision-making. RESULTS: With help from analytical tools
      developed for quality assessment, the workflow process using SPECT/CT may be
      separated into related, but independent steps, each with its specific human and
      material resources to use as inputs or outputs. This helps identify factors that
      could contribute to failure in routine clinical practice. At each step of the
      process, practical aspects to optimise imaging procedure and protocols are
      developed. A decision-making algorithm for justifying each CT indication as well
      as the appropriateness of each CT protocol is the cornerstone of routine clinical
      practice using SPECT/CT. CONCLUSION: In conclusion, implementing hybrid SPECT/CT
      imaging requires new ways of working. It is highly rewarding from a clinical
      perspective, but it also proves to be a daily challenge in terms of management.

PMID- 24318160
TI  - Improving cytopenia with splenic artery embolization in a patient with paroxysmal
      nocturnal hemoglobinuria on eculizumab.
AB  - Paroxysmal nocturnal hemoglobinuria is a rare acquired stem cell disorder
      characterized by intravascular hemolysis, aplasia and an increased risk of
      thrombosis. We describe a patient under treatment with the anti-complement
      antibody eculizumab who developed pancytopenia, requiring blood transfusions, due
      to massive splenomegaly. The patient underwent two separate splenic
      embolizations, which reduced the size of the spleen and improved his blood count
      to the point that blood transfusions were no longer necessary. Splenic
      embolization was chosen over splenectomy due to the potential postoperative
      complications of splenectomy, especially that of thrombosis. 

PMID- 24318159
TI  - Molecular imaging agents for SPECT (and SPECT/CT).
AB  - The development of hybrid single photon emission computed tomography/computed
      tomography (SPECT/CT) cameras has increased the diagnostic value of many existing
      single photon radiopharmaceuticals. Precise anatomical localization of lesions
      greatly increases diagnostic confidence in bone imaging of the extremities,
      infection imaging, sentinel lymph node localization, and imaging in other areas.
      Accurate anatomical localization is particularly important prior to surgery,
      especially involving the parathyroid glands and sentinel lymph node procedures.
      SPECT/CT plays a role in characterization of lesions, particularly in bone
      scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the
      development of novel tracers, SPECT/CT is particularly important in monitoring
      response to therapies that do not result in an early change in lesion size.
      Preclinical SPECT/CT devices, which actually have spatial resolution superior to
      PET/CT devices, have become essential in characterization of the biodistribution
      and tissue kinetics of novel tracers, allowing coregistration of serial studies
      within the same animals, which serves both to reduce biological variability and
      reduce the number of animals required. In conclusion, SPECT/CT increases the
      utility of existing radiopharmaceuticals and plays a pivotal role in the
      evaluation of novel tracers. 

PMID- 24318161
TI  - Quality of life in partners of patients with localised prostate cancer.
AB  - PURPOSE: The diagnosis of prostate cancer and the following treatment does not
      only affect the patient, but also his partner. Partners often suffer even more
      severely from psychological distress than the patients themselves. This analysis
      aims to describe the quality of life (QoL) after the cancer diagnosis over time
      and to identify the effects of possible predictors of partners' quality of life
      in a German study population. DATA AND METHODS: Patients with localised prostate
      cancer and their partners were recruited from a prospective multicenter study in
      Germany, the Prostate Cancer, Sexuality, and Partnership (ProCaSP) Study. At five
      observation times during the follow-up period of 2 years after diagnosis, QoL
      (EORTC QLQ-C30) and personal, social, and cancer-related health factors as well
      as adaptation and coping factors of 293 couples were observed and analysed with
      mixed effects analysis. RESULTS: The men's prostate cancer diagnosis had a small,
      but significant impact on their partner's QoL. However, QoL of partners was most
      affected by the partners' own physical health and psychological condition, time,
      and their relationship quality. CONCLUSION: The finding that average QoL
      increased again 3 months after diagnosis and later should give partners faith and
      hope for the future. The identified most important predictors of partners' QoL
      are potentially susceptible to intervention, and further research on target
      groups in special need of support and on adequate interventions is needed.

PMID- 24318162
TI  - Clinicians' views on factors that trigger a sudden onset of low back pain.
AB  - PURPOSE: Little is known about what triggers an episode of low back pain (LBP) in
      those presenting to primary care. Previous studies of risk factors have focused
      on specific occupational settings and work conditions. No study has asked primary
      care clinicians to consider what triggers an episode of sudden-onset LBP in
      patients presenting to them for care. The purpose of this study, therefore, was
      to describe the short- and long-term factors that primary care clinicians
      consider important in triggering a sudden episode of acute LBP. METHODS: One
      hundred and thirty-one primary care clinicians who were recruiting patients with
      LBP to a large observational study were invited to participate. A questionnaire
      was designed to obtain information about the clinician's characteristics,
      profession and clinical experience. We also asked clinicians to nominate the five
      short- and five long-term exposure factors, most likely to trigger a sudden
      episode of acute LBP, based on their experience. Descriptive statistics and
      frequency distributions were used to describe clinician's characteristics and the
      frequencies of the main risk factor categories were reported. RESULTS: Based on
      the views of 103 primary care clinicians, biomechanical risk factors appear to be
      the most important short-term triggers (endorsed by 89.3% of clinicians) and long
      term triggers (endorsed by 54.2% of clinicians) for a sudden episode of acute
      LBP. Individual risk factors were endorsed by 39% of clinicians as important long
      term triggers, while only 6.4% of clinicians considered them important short-term
      triggers. Other risk factors, such as psychological/psychosocial and genetic
      factors, were not commonly endorsed as risk factors for an episode of LBP by
      primary care clinicians. CONCLUSIONS: This study shows that primary care
      clinicians believe that biomechanical risk factors are the most important short
      term triggers, while biomechanical and individual risk factors are the most
      important long-term triggers for a sudden onset of LBP. However, other risk
      factors, such as psychological/psychosocial and genetic, were not commonly
      endorsed as risk factors for an episode of LBP by primary care clinicians.
      Results of this study are based on primary care clinicians' views and further
      investigation is needed to test the validity of these suggested risk factors.

PMID- 24318163
TI  - Selective pressurized liquid extraction technique capable of analyzing dioxins,
      furans, and PCBs in clams and crab tissue.
AB  - A selective pressurized liquid extraction technique (SPLE) was developed for the
      analysis of polychlorodibenzo-p-dioxins, polychlorodibenzofurans (PCDD/Fs) and
      dioxin-like polychlorobiphenyls (dl-PCBs) in clam and crab tissue. The SPLE
      incorporated multiple cleanup adsorbents (alumina, florisil, silica gel, celite,
      and carbopack) within the extraction cell. Tissue extracts were analyzed by high
      resolution gas chromatography coupled with electron capture negative ionization
      mass spectrometry. Mean recovery (n = 3) and percent relative standard deviation
      for PCDD/Fs and dl-PCBs in clam and crabs was 89 +/- 2.3 and 85 +/- 4.0,
      respectively. The SPLE method was applied to clams and crabs collected from the
      San Jacinto River Waste Pits, a Superfund site in Houston, TX. The dl-PCBs
      concentrations in clams and crabs ranged from 50 to 2,450 and 5 to 800 ng/g ww,
      respectively. Sample preparation time and solvents were reduced by 92 % and 65 %,
      respectively, as compared to USEPA method 1613.

PMID- 24318164
TI  - Characteristics of a microcystin-LR biodegrading bacterial isolate: Ochrobactrum
      sp. FDT5.
AB  - Mass growth of blue-green algae in eutrophic water bodies leads to a large amount
      of toxins, e.g. microcystins (MCs). How to remove MCs from water bodies is an
      environmental problem. In this study, an algicidal bacterium Ochrobactrum sp.
      FDT5 was isolated and found to have microcystin-LR (MC-LR) degradation capacity,
      which could be enhanced by a domestication process. The FDT5 cell density, MC-LR
      initial concentration, temperature, and pH on the degradation of MC-LR were
      investigated. The results indicated that the initial cell density of FDT5 and the
      initial concentration of MC-LR could influence MC-LR degradation. The optimum
      conditions were under the temperature of 35 degrees C with pH of 7.0. After FDT5
      was exposed to MC-LR for 2 days, FDT5 cells produced active cellular components
      that degraded MC-LR. These cellular components were heat-inactivated and removed
      when FDT5 cells were removed by filtration.

PMID- 24318165
TI  - The prevalence, radiographic appearance, and characteristics of zygomatic air
      cell defects (ZACDs) in symptomatic temporomandibular joint disorder patients in
      North Indian population.
AB  - PURPOSE: Although the incidence of zygomatic air cell defects (ZACDs) is
      significantly low in general population, still they pose as a risk factor during
      surgical procedures like eminectomies and eminoplasties because there is a risk
      of spread of infection intracranially. Furthermore, such procedures are more
      common in TMD patients. With this fact in mind, this study was designed to find
      out the prevalence, radiographic appearance, and characteristics of zygomatic air
      cell defects in diagnosed symptomatic temporomandibular joint disorder patients.
      METHOD: The study comprised of evaluation of panoramic radiographs of 70
      temporomandibular joint disorder (TMD) patients in the age range of 18-30 years
      selected on the basis of Research Diagnostic Criteria (RDC/TMD). The radiographs
      were evaluated regarding the presence, variations, and characteristics of ZACDs.
      Groups were compared by chi (2) analysis. RESULTS: ZACDs were identified in 21
      TMD subjects out of 70, giving an overall prevalence of 30 %. Out of 21 ZACDs,
      nine were in males (42.8 %) and 12 were in females (52.38 %). ZACDs were
      unilateral in ten TMD patients (47.61 %) and were bilateral in 11 patients (52.38
      %). CONCLUSION: It can be concluded that the number of ZACDs is surprisingly more
      in diagnosed TMD patients. This strengthens the need for thorough preoperative
      imaging evaluation of ZACDs in such patients. Further longitudinal studies are
      required to find out the long-term effect of ZACDs on symptomatic as well as non
      symptomatic TMD subjects. This may prove helpful to appreciate that whether ZACDs
      have any role in the development TMDs and vice versa. As with many TMD studies,
      caution should be exercised in interpreting these results until further studies
      have been carried out on this topic. Ideally, some prospective randomised
      evaluations with "hard" evidence of the diagnosis with MRI support.

PMID- 24318166
TI  - Outcomes toolbox for head and neck cancer research.
AB  - BACKGROUND: Clinical research in head and neck cancer traditionally focused on
      tumor control. As survival improves, it is increasingly recognized that the side
      effects of multimodality treatment can be profound and enduring. Thus, clinical
      trials require patient-reported and functional outcomes. METHODS: A subcommittee
      of the Previously Untreated, Locally Advanced (PULA) Task Force of the Head and
      Neck Steering Committee of the Coordinating Centre for Clinical Trials at the
      National Cancer Institute (NCI) was convened to identify a set of instruments
      suitable for widespread application in the conduct of clinical trials for head
      and neck cancer. RESULTS: Based on existing literature and expert opinion, 18
      main areas of concern were identified. For each, measures suitable for use in
      multicenter clinical trials were recommended on the basis of validity,
      feasibility, and clinical acceptance. CONCLUSION: Suitable instruments exist for
      most head and neck cancer concerns, but gaps require further development. Future
      efforts should be made to harmonize measurement across trials.

PMID- 24318167
TI  - Biogenic amines formation, nucleotide degradation and TVB-N accumulation of
      vacuum-packed minced sturgeon (Acipenser schrencki) stored at 4  degrees C and
      their relation to microbiological attributes.
AB  - BACKGROUND: Sturgeon (Acipenser schrencki) were filleted, minced, vacuum-packed
      and stored at 4  degrees C. Minced sturgeon muscles were analysed for 10 days to
      determine biochemical [eight biogenic amines, ATP and breakdown products, K
      value, total volatile basic nitrogen (TVB-N) and pH], microbiological (total
      viable counts, Enterobacteriaceae, Psychrotrophs, Pseudomonas, Aeromonas, Vibrio,
      Lactobacillus and Brochothrix thermosphacta) changes and their relationships.
      RESULTS: The shelf-life of sturgeon was found to be 3-4 days according to
      microbiological assessment. At the end of the storage, Psychrotrophs,
      Enterobacteriaceae and Aeromonas became the dominant bacteria, reaching 7.85,
      7.98 and 8.02 log cfu g(-1), respectively. Biogenic amines, hypoxanthine and the
      K value increased significantly (P < 0.05) during the storage. Putrescine and
      cadaverine was the dominant biogenic amines while tryptamine was not detected
      during the storage. In addition, putrescine, cadaverine and hypoxanthine were
      highly related to storage time and total viable counts (r(2), 0.876-0.962),
      indicating that they can be good biomarkers for quality assessment of vacuum
      packed minced sturgeon stored at 4  degrees C. CONCLUSION: In this study, key
      biochemical and microbiological attributes were established to monitor the
      spoilage and shelf life of vacuum-packed sturgeon. These results could help to
      establish better cold storage management of minced sturgeon products under
      commercial conditions.

PMID- 24318168
TI  - The pre-ejection period during the Muller manoeuvre: mismatch or misreading?

PMID- 24318170
TI  - Women's perceptions about female reproductive system: a survey from an academic
      obstetrics and gynecology practice.
AB  - OBJECTIVE: To assess women's knowledge about female reproductive system and the
      demographic factors that may influence their perceptions. STUDY DESIGN: In this
      cross-sectional study, all qualifying adult women at our academic practice were
      asked to complete a self-administered anonymous questionnaire about the effects
      of female reproductive system between June and August 2009. We assessed the
      accuracy of their knowledge and analyzed the effect of demographic factors.
      RESULTS: The majority of the 500 participants were in 18- to 59-year age range
      (93 %), Caucasian (81 %), married (56 %), college graduates (74 %) and had
      private insurance (82 %). Mean correct score was 63 +/- 20 %. In univariate
      analysis, those respondents who were older, Caucasian, and had private insurance
      scored significantly higher (p < 0.05) When all the variables were entered in a
      fractional logit model, only age, race and reason for the visit remained as
      independent predictors for a better overall score in this survey. Twenty-nine
      percent of the participants thought hysterectomy included removal of ovaries and
      tubes. About a quarter of the respondents thought menstrual function would
      continue after hysterectomy. The question for whether removal of the uterus
      resulted in climacteric changes was correctly answered only by 34 %. While 59 %
      of women did not agree that removing the entire uterus eliminated the cervical
      cancer risk, 66 % concluded that they would continue to need Pap smears after
      total hysterectomy. CONCLUSION: Women's knowledge about female reproductive
      system is limited, especially for those who are younger and from a minority.

PMID- 24318169
TI  - Colonization of the lower urogenital tract with Ureaplasma parvum can cause
      asymptomatic infection of the upper reproductive system in women: a preliminary
      study.
AB  - PURPOSE: Genital ureaplasmas are considered opportunistic pathogens of human
      genitourinary tract involved in adverse pregnancy sequelae and infertility. While
      association of Ureaplasma urealyticum with urogenital tract infections is well
      established, the role of Ureaplasma parvum in these infections is still
      insufficient. In the study, we compared how often cervicovaginal colonization
      with U. parvum is associated with the presence of these microorganisms in the
      upper genitourinary tract of fertile and infertile women. METHODS: We used PCR
      assay to determine the prevalence of U. parvum and U. urealyticum in pairs of
      specimens, i.e., vaginal swabs and Douglas' pouch fluid samples from consecutive
      40 women with no symptoms of genital tract infection. RESULTS: In total, 19 (47.5
      %) of the 40 samples were positive for ureaplasmas. U. parvum was simultaneously
      detected in pairs of samples in five (55.5 %) of the nine (47.4 %) women positive
      in PCR assay. As many as 5 (18.5 %) of the 27 infertile women and 1 (7.7 %) of
      the 13 fertile women showed infection of the upper genital tract with U. parvum.
      CONCLUSION: The results of the study demonstrated that colonization of the lower
      genital tract with U. parvum can produce asymptomatic infection of the upper
      reproductive system in women. These findings also imply that U. parvum may be
      present in the upper genital tract at the time of conception and might be
      involved in adverse pregnancy outcomes.

PMID- 24318171
TI  - Evaluation of a PEG/hydroxypropyl starch aqueous two-phase system for the
      separation of monoclonal antibodies from cell culture supernatant.
AB  - In this study, an aqueous two-phase system (ATPS) with PEG and hydroxypropyl
      starch (HPS) was used to separate monoclonal antibody (mAb) from Chinese hamster
      ovary cell culture supernatant. The phase diagram of the PEG/HPS ATPS was
      determined, and the effects of NaCl addition were investigated. The results
      showed that NaCl addition could lead to a shift of the binodal curve and that
      phase separation would occur at higher PEG and HPS concentrations. The effects of
      NaCl addition, pH, and the load of cell supernatant on the partitioning of mAb in
      a PEG/HPS ATPS were investigated. It was found that with 6% cell supernatant and
      15% NaCl addition at pH 6.0, the yield of mAb in the upper phase was 96.7% with a
      purity of 96.0%. The back-extraction of mAb with a PEG/phosphate ATPS were also
      studied, and the results showed that after the two-step extraction with ATPSs the
      purity of mAb could reach 97.6 +/- 0.5% with a yield of 86.8 +/- 1.0%, which was
      comparable to the purification with Protein A chromatography. These results
      indicate that the two-step extraction with PEG/HPS and PEG/phosphate ATPSs might
      be a promising alternative for the separation of mAb from cell culture
      supernatant. 

PMID- 24318172
TI  - Reporting complications and outcome, are we there yet?

PMID- 24318173
TI  - 25th anniversary article: exploring nanoscaled matter from speciation to phase
      diagrams: metal phosphide nanoparticles as a case of study.
AB  - The notions of nanoscale "phase speciation" and "phase diagram" are defined and
      discussed in terms of kinetic and thermodynamic controls, based on the case of
      metal phosphide nanoparticles. After an overview of the most successful synthetic
      routes for these exotic nanomaterials, the cases of InP, Ni2 P, Ni12 P5 and Pdx
      Py are discussed in detail to highlight the relationship between composition,
      structure, and size at the nanoscale. The influence of morphology is discussed
      next by comparing the behavior of Cu3 P nanophases with those of Nix Py , FeP/Fe2
      P, and CoP/Co2 P. Perspectives provide the reader with methodological guidelines
      for further investigation of nanoscale "phase diagrams", and their use for
      optimized synthesis of new functional nanomaterials. 

PMID- 24318175
TI  - Abscisic-acid and gibberellin action in developing kernels of triticale (cv.
      6A190).
AB  - Abscisic-acid (ABA) levels were determined in triticale 6A190 kernels at various
      stages of development from anthesis to maturity. ABA reached a maximum at ca. 22
      d post-anthesis and declined rapidly 12 d later. Associated with drying of the
      kernel at maturity there was a rapid increase in the endogenous level of alpha
      amylase, apparently based upon de-novo synthesis. Simultaneously there were
      visible signs of degradation of the large starch grains in the starchy endosperm.
      Regulation of alpha-amylase production in the kernel by exogenous gibberellic
      acid (GA3) was only evident in the almost mature kernel (30-40 d after anthesis)
      and then only if these kernels were first dried artificially. Furthermore, little
      alpha-amylase mRNA could be detected prior to kernel maturity and water loss.
      Thus, the high levels of gibberellin (GA) that have been found early in kernel
      development in cereals do not appear to control the later production of alpha
      amylase and onset of kernel germination in the ear of triticale. However, the
      presence of high levels of ABA until maturity could prevent early germination and
      premature production of alpha-amylase. Kernels of triticale 6A190 are
      characteristically shrivelled and non-dormant at maturity. The relevance of
      changes in the capacity of kernels to respond to and produce GA and ABA is
      discussed in relation to problems of harvest dormancy in cereals. 

PMID- 24318176
TI  - The role of retinol in the initiation of sporangiophores of Phycomyces
      blakesleeanus.
AB  - The initiation of sporangiophores of Phycomyces was analyzed under oxygen
      limiting conditions. Mutants lacking beta-carotene have a higher oxygen threshold
      than the wild type depending on the residual amount of beta-carotene. The
      supersensitivity to low oxygen tension is specific for sporangiophore initiation
      and can be suppressed by addition of either retinal, retinol or retinol acetate
      to the medium. It is suggested that retinol is a natural regulator of
      differentiation in Phycomyces. 

PMID- 24318177
TI  - Solubilized auxin-binding protein : Subcellular localization and regulation by a
      soluble factor from homogenates of corn shoots.
AB  - Discontinuous sucrose gradient fractionations indicate that the high-affinity
      auxin binding protein which can be solubilized from the microsomes of coleoptiles
      and primary leaves of Zea mays L. seedlings is probably located in the
      endoplasmic reticulum (ER). Since aromatic hydroxylations are enzymatic
      activities typical of the ER of plant cells, we have examined the effects of
      several electron-transport inhibitors on the binding of 1-naphthylacetic acid
      (NAA). NaN3 strongly inhibits this binding, but KCN and CO do not. Trans-cinnamic
      acid and trans-p-coumaric acid, which are the substrates of ER hydroxylase
      activities in plants (but which are themselves not auxins), also inhibit this
      binding. Supernatant fractions from corn shoots contain factors inhibitory to the
      binding of NAA to the intact membranes and solubilized Site I auxin-binding
      protein. Here we show that these factors are competitive inhibitors of the
      binding of [(14)C]NAA but do not change the apparent affinity of the protein for
      indoleacetic acid, 2,4-dichlorophenoxyacetic acid or naphthoxyacetic acid.
      Several tissues were assayed for factors inhibitory to auxin binding to the
      solubilized protein, but only supernants from corn shoots were markedly
      inhibitory at low concentrations. 

PMID- 24318178
TI  - Effects of ophiobolin B on cell enlargement and H(+)/K (+) exchange in maize
      coleoptile tissues.
AB  - Ophiobolin B (OPH B), a sesterpene metabolite of Helminthosporium oryzae,
      inhibits proton extrusion from maize coleoptiles. Moreover OPH B counteracts the
      biological activity of fusicoccin (FC), another terpenoid toxin produced by
      Fusicoccum amygdali having a similar basic chemical structure: OPH B inhibits FC
      promoted proton extrusion, potassium uptake and cell enlargement.The findings
      suggest that the effect of OPH B in stimulating electrolites, glucose and
      aminoacid leakage, reported in a previous paper, can be explained by the capacity
      of the toxin to inhibit proton extrusion. 

PMID- 24318179
TI  - Hydroxyproline: its asymmetric distribution in a cell wall glycoprotein.
AB  - The main structural glycoprotein of the cell wall of Chlamydomonas reinhardii has
      been cleaved by thermolysin into glycopeptides which have been separated into
      three fractions, T1, T2 and T3. These correspond to three distinct domains within
      the glycoprotein, characterized by the asymmetric distribution of both sugars and
      amino acids, in particular hydroxyproline. T2 is very rich in hydroxyproline (43
      mol %) and is highly glycosylated, while T3 is poor in hydroxyproline and
      contains very little carbohydrate. The results are discussed in terms of cell
      wall glycoproteins and their function. 

PMID- 24318180
TI  - Photoregulation of the incorporation of guaiacyl units into lignins.
AB  - When fed with [(14)C] phenylalanine in the light, xylem tissues isolated from
      poplar stems were able to incorporate part of the radioactivity into both the
      guaiacyl and the syringyl residues of lignins. In the dark, only syringyl units
      were integrated into the polymer whereas the guaiacyl residues remained
      unlabeled.When a membrane perturber (isopropanol) was added to the incubation
      mixture, the label was incorporated into the guaiacyl units either in the light
      or in the dark. Conversely, a membrane stabilizer (CaCl2) prevented the labeling
      of the guaiacyl units even when the tissues were illuminated. These results
      suggest that light acts through the modification of membrane permeabilities,
      altering specifically the synthesis and the transport or the polymerization of
      guaiacyl-type units during the process of lignification. 

PMID- 24318181
TI  - Nitrate uptake and nitrate reduction in synchronous Chlorella.
AB  - Nitrate uptake was followed continuously in cultures of Chlorella sorokiniana
      using ionsensitive electrodes. During the lifecycle of the synchronous cell
      cultures, a drastic increase occurred in the first hour after the onset of the
      light. Nitrate uptake rate was shown to be dependent on illumination intensity,
      nitrate concentration, and temperature. These results point to an energy-linked
      uptake process. From the different timecourses of nitrate uptake rate and nitrate
      reductase activation, one can conclude that the increased nitrate reductase
      activity after light onset is regulated via nitrate uptake. Further evidence for
      a regulation in this direction is shown by the action of ammonium on nitrate
      uptake and nitrate reductase activity. The results are discussed in terms of the
      regulation of the nitrate consuming system. 

PMID- 24318182
TI  - Ethylene formation from 1-aminocyclopropane-1-carboxylic acid in homogenates of
      etiolated pea seedlings.
AB  - Homogenates of etiolated pea (Pisum sativum L.) shoots formed ethylene upon
      incubation with 1-aminocyclopropane-1-carboxylic acid (ACC). In-vitro ethylene
      formation was not dependent upon prior treatment of the tissue with indole-3
      acetic acid. When homogenates were passed through a Sephadex column, the
      excluded, high-molecular-weight fraction lost much of its ethylene-synthesizing
      capacity. This activity was largely restored when a heat-stable, low-molecular
      weight factor, which was retarded on the Sephadex column, was added back to the
      high-molecular-weight fraction. The ethylene-synthesizing system appeared to be
      associated, at least in part, with the particulate fraction of the pea
      homogenate. Like ethylene synthesis in vivo, cell-free ethylene formation from
      ACC was oxygen dependent and inhibited by ethylenediamine tetraacetic acid, n
      propyl gallate, cyanide, azide, CoCl3, and incubation at 40 degrees C. It was
      also inhibited by catalase. In-vitro ethylene synthesis could only be saturated
      at very high ACC concentrations, if at all. Ethylene production in pea
      homogenates, and perhaps also in intact tissue, may be the result of the action
      of an enzyme that needs a heat-stable cofactor and has a very low affinity for
      its substrate, ACC, or it may be the result of a chemical reaction between ACC
      and the product of an enzyme reaction. Homogenates of etiolated pea shoots also
      formed ethylene with 2-keto-4-mercaptomethyl butyrate (KMB) as substrate.
      However, the mechanism by which KMB is converted to ethylene appears to be
      different from that by which ACC is converted. 

PMID- 24318183
TI  - The effect of ethylene and auxin on cell wall extensibility of the Semi-aquatic
      fern, Regnellidium diphyllum.
AB  - Ethylene and auxin both enhance cell elongation growth in the rachis of the frond
      of Regnellidium diphyllum. Measurements of the stress relaxation modulus of the
      walls of methanol-killed rachis segments show that both auxin and ethylene cause
      an increase in cell wall extensibility, that the effects are additive, and that
      they occur in the presence of hypertonic solutions of mannitol that preclude cell
      elongation. The results are taken as evidence for the operation of two separate
      mechanisms for cell wall loosening. 

PMID- 24318184
TI  - Ethylene and auxin-induced cell growth in relation to auxin transport and
      metabolism and ethylene production in the semi-aquatic plant, Regnellidium
      diphyllum.
AB  - Cell elongation in the rachis of the semiaquatic fern Regnellidium diphyllum is
      induced by the addition of ethylene or indoleacetic acid (IAA). Experiments with
      whole plants or rachis segments have shown that ethylene-induced growth requires
      the presence of auxin. Ethylene does not cause a modification in either
      endogenous auxin levels or in the extent of auxin metabolism but auxin transport
      is reduced. Rates of ethylene production in Regnellidium are not altered by
      either mechanical excitation or by the addition of auxin. A two-hormone control
      of cell expansion is proposed in which an initial, auxin-dependent growth event
      pre-conditions the cells to a further subsequent (or synchronous) ethylene
      dependent growth event. 

PMID- 24318185
TI  - Short-term and long-term effects of plant water deficits on stomatal response to
      humidity in Corylus avellana L.
AB  - Short-term (hours) changes in plant water status were induced in hazel (Corylus
      avellana L.) by changing the evaporative demand on a major portion of the shoot
      while maintaining a branch in a constant environment. Stomatal conductance of
      leaves on the branch was influenced little by these short-term changes in water
      status even with changes in leaf water potential as great as 8 bars. Long-term
      (days) changes in plant water status were imposed by soil drying cycles. Stomatal
      conductance progessively decreased with increases in long-term water stress.
      Stomata still responded to humidity with long-term water stress but the range of
      the conductance response decreased. Threshold responses of stomata to leaf water
      potential were not observed with either short-term or long-term changes in plant
      water status even when leaves wilted. It is suggested that concurrent
      measurements of plant water status may not be sufficient for explaining stomatal
      and other plant responses to drought. 

PMID- 24318186
TI  - Pathways of carbohydrate fermentation in the roots of marsh plants.
AB  - We did this work to discover the pathways of carbohydrate fermentation in
      unaerated roots of three species of flood-tolerant plants, Ranunculus sceleratus,
      Glyceria maxima, and Senecio aquaticus. The experiments were done with the apical
      1-2 cm of the roots and the results for the three species were similar. The
      maximum catalytic activities of alcohol dehydrogenase, lactate dehydrogenase,
      phosphoenolpyruvate carboxylase, NADP-dependent malic enzyme, and
      phosphofructokinase were appreciable and roughly comparable. Reduced aeration of
      the roots led to 1.5 to 5-fold increases in the maximum catalytic activities of
      alcohol dehydrogenase, small increases in those of lactate dehydrogenase in two
      species, and no increase in those of phosphoenolpyruvate carboxylase and
      phosphofructokinase. Phosphoenolpyruvate carboxykinase could not be detected.
      Metabolism of [U-(14)C]sucrose under anaerobic conditions by excised roots, grown
      without aeration, led to appreciable labelling of ethanol and alanine, slight but
      significant labelling of lactate, and minimal labelling of malate and related
      organic acids. Incubation of similar excised roots under anaerobic conditions for
      4 h caused marked accumulation of ethanol, smaller accumulation of lactate, and
      no detectable accumulation of malate. We conclude that in all three species
      fermentation of carbohydrate results in the accumulation of predominant amounts
      of ethanol, smaller amounts of lactate, no significant quantities of malate, and
      probably appreciable amounts of alanine. Crawford's metabolic theory of flooding
      tolerance is held to be incompatible with these results. 

PMID- 24318187
TI  - Degradation of the endosperm cell walls of Lactuca sativa L., cv. grand rapids in
      relation to the mobilisation of proteins and the production of hydrolytic enzymes
      in the axis, cotyledons and endosperm.
AB  - The timing of changes in total nitrogen and soluble amino nitrogen content, and
      in the activities of proteinase (pH 7.0), isocitrate lyase, catalase, phytase,
      phosphatase (pH 5.0), alpha-galactosidase and beta-mannosidase were studied in
      extracts from the cotyledons, axis and endosperms of germinating and germinated
      light-promoted lettuce seeds. The largest amount of total nitrogen (2.7% seed dry
      weight) occurs within the cotyledons, as storage protein. As this decreases the
      total nitrogen content of the axis increases and the soluble amino nitrogen in
      the cotyledons and axis increases. Proteinase activity in the cotyledons
      increases coincidentally with the depletion of total nitrogen therein. Enzymes
      for phytate mobilisation and for gluconeogenesis of hydrolysed lipids increase in
      activity in the cotyledons as the appropriate stored reserves decline. Beta
      mannosidase, an enzyme involved in the hydrolysis of oligo-mannans released by
      the action of endo-beta-mannase on mannan reserves in the endosperm, arises
      within the cotyledons. This indicates that complete hydrolysis of mannans to the
      monomer does not occur within the endosperm. Mobilisation of all cotyledon
      reserves occurs after the endosperm has been degraded, providing further evidence
      that the endosperm is an early source of food reserves for the growing embryo. 

PMID- 24318188
TI  - Phonolic components of the primary cell wall and their possible role in the
      hormonal regulation of growth.
AB  - The insoluble cell wall polymers of cultured spinach cells contained esterified
      ferulic acid at 2-5 mg g(-1) dry weight. Gibberellic acid (GA3, 10(-11)-10(-6) M)
      promoted the expansion of these cells and simultaneoulsy suppressed peroxidase
      secretion, reduced the activity of cellular phenylanine ammonia-lyase and
      favoured the accumulation of wall-esterified ferulate and of extracellular
      soluble phenolic aglycones. When growth was prevented with 0.7 M sorbitol, GA3
      still evoked the phenolic and peroxidase effects. It is suggested that peroxidase
      restricts growth by rigidifying the cell wall in two ways: (a) covalently by
      catalysing the conversion of feruloyl side-chains into diferuloyl cross-links and
      (b) non-covalently by catalysing the conversion of soluble phenolics into
      hydrophobic quinones (or polymers). GA3 is hypothesised to prevent this
      rigidification by inhibiting peroxidase secretion. 

PMID- 24318189
TI  - Interaction of [(3)H]gibberellin A 1 with a sub-cellular fraction from lettuce
      (Lactuca sativa L.) hypocotyls : I. Kinetics of labelling.
AB  - The distribution of [(3)H]gibberellin A1 ([(3)H]GA1) amongst sub-cellular
      fractions from lettuce (Lactuca sativa L.) hypocotyl sections was examined by
      differential centrifugation. Material pelleting at 2000 g (2KP) accounted for 2
      5% of the total tissue radioactivity and no other significant interactions were
      detected. After rigorous washing procedures, the 2KP fraction was found to
      consist mainly of cell wall material and the radioactivity remained associated
      during sucrose density-gradient centrifugation. 2KP-labelling increased linearly
      with time and was only partially removed by chasing for up to 40 h in the
      presence of unlabelled GA1. A linear plot was obtained for the relationship
      between external concentration and the log of 2KP GA1 content with a maximum
      percentage incorporation at 10(-5) mol 1(-1). Incorporation of radioactivity was
      reduced by chasing with unlabelled GA1 or GA9, but not by GA8. Labelling of the
      2KP fraction increased uniformly with temperature between 15 degrees C and 30
      degrees C but showed little change below 15 degrees C. Growth rate and 2KP
      labelling were highly correlated (r=0.989). The possible significance of these
      findings is discussed. 

PMID- 24318190
TI  - Interaction of [(3)H] gibberellin A 1 with a sub-cellular fraction from lettuce
      (Lactuca sativa L.) hypocotyls : II. Stability and properties of the association.
AB  - Radioactive 2,000 g pellets (2KP) derived from lettuce (Lactuca sativa) hypocotyl
      sections incubated with [(3)H]gibberellin A1 ([(3)H]GA1) were subjected to a
      range of treatments to test the stability of labelling. The labelled association
      was stable in 0.1 M buffer at pH 3 and pH 9 and also in 1 M salt, organic
      solvents, protease or cellulase. Both 1 M potassium hydroxide (KOH) and a
      quaternary ammonium hydroxide tissue solubiliser effected an 80% release of
      incorporated [(3)H]. No radioactivity was released during polyacrylamide gel
      electrophoresis. Gel chromatography of KOH digests indicated the presence of
      labelled compounds with a higher molecular weight than GA1. This material
      remained near to the origin during high-voltage paper electrophoresis.
      Calculations based upon KOH extraction of 2KP material suggested that 5 to 20% of
      the total uptake of [(3)H]GA1 could be recovered from this fraction. The
      implications of these findings are discussed. 

PMID- 24318191
TI  - The effect of light pretreatments on phytochrome-mediated induction of
      anthocyanin and of phenylalanine ammonia-lyase.
AB  - Induction by light of phenylalanine ammonia-lyase (PAL; EC 4.3.1.5) and of
      anthocyanin in cotyledons of the mustard (Sinapis alba L.) seedling is strongly
      affected by a light pretreatment which operates through phytochrome. If PAL or
      anthocyanin is induced by a light pulse, the effectiveness of phytochrome (Pfr)
      is strongly increased by a light pretreatment; however, if the increase of the
      PAL level or synthesis of anthocyanin is elicited by continuous far-red light
      (operating via phytochrome in the 'High Irradiance Response'), effectiveness of
      light is strongly reduced by the same light pretreatment. This reduction of
      effectiveness is correlated with a decrease of total phytochrome (Ptot) caused by
      the light pretreatment. It is argued that the observations are compatible only
      with the 'open phytochrome-receptor model' as suggested by Schafer (J. Mathem.
      Biol. 2, 41-56, 1975). The peaks of the time courses of the PAL levels under
      continous far-red light are located at 48 h after sowing and do not depend on the
      original level of phytochrome. The decrease of the PAL levels beyond 48 h after
      sowing takes place independently of phytochrome and of the actual level of PAL. 

PMID- 24318193
TI  - Sustained growth factor delivery in tissue engineering applications.
AB  - The beautifully orchestrated complexity of the temporal spatial growth factor
      gradients during embryogenesis offer a striking contrast to systemic bolus
      administration that lack tissue specificity and sustained protein localization,
      often requiring supraphysiological protein doses to produce the desired
      therapeutic dose. These attributes may be responsible for clinically observed
      dangerous tissue overgrowth, inflammation, and even tumor formation. Growth
      factor delivery within an implanted scaffold is a very attractive way to modulate
      cell behavior. For short term delivery, proteins can be non-specifically adsorbed
      to the material surface or simply entrapped within the bulk scaffold. For more
      sustained delivery, many researchers have turned to the ever increasing list of
      covalent immobilization methods that have profound applications in purification,
      biosensing, imaging, and drug discovery by tethering proteins, nucleic acids,
      carbohydrates, synthetic polymers, small molecules, nanotubes, and even whole
      cells. This review focuses on the use of covalent immobilization to achieve
      sustained growth factor delivery for tissue engineering. Covalent immobilization
      techniques will be reviewed in terms of design, protein bioactivity/stability,
      efficiency, and spatiotemporal distribution. Further, the biological response to
      sustained growth factor delivery will also be covered, such as cell interaction,
      cell responsiveness, proliferation, differentiation, extracellular matrix
      production, and tissue regeneration. This focused review is anticipated to inform
      investigators on the selection of optimal immobilization strategies for their
      specific applications.

PMID- 24318192
TI  - Airflow and particle deposition simulations in health and emphysema: from in vivo
      to in silico animal experiments.
AB  - Image-based in silico modeling tools provide detailed velocity and particle
      deposition data. However, care must be taken when prescribing boundary conditions
      to model lung physiology in health or disease, such as in emphysema. In this
      study, the respiratory resistance and compliance were obtained by solving an
      inverse problem; a 0D global model based on healthy and emphysematous rat
      experimental data. Multi-scale CFD simulations were performed by solving the 3D
      Navier-Stokes equations in an MRI-derived rat geometry coupled to a 0D model.
      Particles with 0.95 MUm diameter were tracked and their distribution in the lung
      was assessed. Seven 3D-0D simulations were performed: healthy, homogeneous, and
      five heterogeneous emphysema cases. Compliance (C) was significantly higher (p =
      0.04) in the emphysematous rats (C = 0.37 +/- 0.14 cm(3)/cmH2O) compared to the
      healthy rats (C = 0.25 +/- 0.04 cm(3)/cmH2O), while the resistance remained
      unchanged (p = 0.83). There were increases in airflow, particle deposition in the
      3D model, and particle delivery to the diseased regions for the heterogeneous
      cases compared to the homogeneous cases. The results highlight the importance of
      multi-scale numerical simulations to study airflow and particle distribution in
      healthy and diseased lungs. The effect of particle size and gravity were studied.
      Once available, these in silico predictions may be compared to experimental
      deposition data. 

PMID- 24318194
TI  - Dominant-negative effects of KCNQ2 mutations are associated with epileptic
      encephalopathy.
AB  - OBJECTIVE: Mutations in KCNQ2 and KCNQ3, encoding the voltage-gated potassium
      channels KV 7.2 and KV 7.3, are known to cause benign familial neonatal seizures
      mainly by haploinsufficiency. Here, we set out to determine the disease mechanism
      of 7 de novo missense KCNQ2 mutations that were recently described in patients
      with a severe epileptic encephalopathy including pharmacoresistant seizures and
      pronounced intellectual disability. METHODS: Mutations were inserted into the
      KCNQ2 cDNA. Potassium currents were recorded using 2-microelectrode voltage
      clamping, and surface expression was analyzed by a biotinylation assay in cRNA
      injected Xenopus laevis oocytes. RESULTS: We observed a clear loss of function
      for all mutations. Strikingly, 5 of 7 mutations exhibited a drastic dominant
      negative effect on wild-type KV 7.2 or KV 7.3 subunits, either by globally
      reducing current amplitudes (3 pore mutations) or by a depolarizing shift of the
      activation curve (2 voltage sensor mutations) decreasing potassium currents at
      the subthreshold level at which these channels are known to critically influence
      neuronal firing. One mutation significantly reduced surface expression.
      Application of retigabine, a recently marketed KV 7 channel opener, partially
      reversed these effects for the majority of analyzed mutations. INTERPRETATION:
      The development of severe epilepsy and cognitive decline in children carrying 5
      of the 7 studied KCNQ2 mutations can be related to a dominant-negative reduction
      of the resulting potassium current at subthreshold membrane potentials. Other
      factors such as genetic modifiers have to be postulated for the remaining 2
      mutations. Retigabine or similar drugs may be used as a personalized therapy for
      this severe disease.

PMID- 24318196
TI  - Long-term implant survivorship of cementless total knee arthroplasty: a
      systematic review of the literature and meta-analysis.
AB  - Cementless total knee arthroplasty (TKA) has had limited use in the United
      States, however, recent reports have demonstrated promising results, but there
      has been no meta-analysis to examine these outcomes in the past 5 years. In this
      review, 37 studies (2,940 patients and 3,568 TKAs) were identified and used,
      comparing cementless to cemented TKA. Pooled implant survivorship was compared
      using a fixed-effect meta-analysis between cementless and cemented TKA, and
      between cementless TKA with and without screw fixation. Cementless TKA had
      implant survivorship comparable to cemented TKA (odds ratio, 1.1; 95% confidence
      interval [CI], 0.62-2.00). The mean survivorship at 10 years for cementless TKA
      was 95.6% compared with 95.3% for cemented TKA. At 20-year follow-up, implant
      survivorship decreased to 76 and 71%, respectively. No difference was observed
      between fixation with or without screws (OR, 1.1; 95% CI, 0.16-7.5). Implant
      survivorship for cementless TKA was comparable to the current gold standard
      cemented TKAs. 

PMID- 24318195
TI  - Endothelial hypoxic metabolism in carcinogenesis and dissemination: HIF-A
      isoforms are a NO metastatic phenomenon.
AB  - Tumor biology is a broad and encompassing field of research, particularly given
      recent demonstrations of the multicellular nature of solid tumors, which have led
      to studies of molecular and metabolic intercellular interactions that regulate
      cancer progression. Hypoxia is a broad stimulus that results in activation of
      hypoxia inducible factors (HIFs). Downstream HIF targets include angiogenic
      factors (e.g. vascular endothelial growth factor, VEGF) and highly reactive
      molecules (e.g. nitric oxide, NO) that act as cell-specific switches with unique
      spatial and temporal effects on cancer progression. The effect of cell-specific
      responses to hypoxia on tumour progression and spread, as well as potential
      therapeutic strategies to target metastatic disease, are currently under active
      investigation. Vascular endothelial remodelling events at tumour and metastatic
      sites are responsive to hypoxia, HIF activation, and NO signalling. Here, we
      describe the interactions between endothelial HIF and NO during tumor growth and
      spread, and outline the effects of endothelial HIF/NO signalling on cancer
      progression. In doing so, we attempt to identify areas of metastasis research
      that require attention, in order to ultimately facilitate the development of
      novel treatments that reduce or prevent tumour dissemination. 

PMID- 24318197
TI  - Lipid effects on expulsion rate of amphotericin B from solid lipid nanoparticles.
AB  - We aimed to investigate the effects that natural lipids, theobroma oil (TO) and
      beeswax (BW), might have on the physical properties of formulated nanoparticles
      and also the degree of expulsion of encapsulated amphotericin B (AmB) from the
      nanoparticles during storage. Lecithin and sodium cholate were used as
      emulsifiers whilst oleic acid (OA) was used to study the influence of the state
      of orderliness/disorderliness within the matrices of the nanoparticles on the
      degree of AmB expulsion during storage. BW was found to effect larger z-average
      diameter compared with TO. Lecithin was found to augment the stability of the
      nanoparticles imparted by BW and TO during storage. An encapsulation efficiency
      (%EE) of 59% was recorded when TO was the sole lipid as against 42% from BW. In
      combination however, the %EE dropped to 39%. When used as sole lipid, TO or BW
      formed nanoparticles with comparatively higher enthalpies, 21.1 and 23.3 J/g
      respectively, which subsequently caused significantly higher degree of AmB
      expulsion, 81 and 83% respectively, whilst only 11.8% was expelled from a binary
      TO/BW mixture. A tertiary TO/BW/OA mixture registered the lowest enthalpy at 8.07
      J/g and expelled 12.6% of AmB but encapsulated only 22% of AmB. In conclusion,
      nanoparticles made from equal concentrations of TO and BW produced the most
      desirable properties and worthy of further investigations. 

PMID- 24318198
TI  - Age segregation of adolescents in and out of school.
AB  - In a naturalistic study of age segregation during adolescence, 403 adolescents
      making up 153 separate groups were observed in three high schools and seven out
      of-school settings. Age segregation was extensive, especially in school, among
      older adolescents in same-sex groups of friends. More mixed-age association was
      observed out of school among younger adolescents who were in mixed-sex groups
      containing relatives. Adolescents were most often observed with friends who were
      other adolescents, next with adults, and least frequently observed with children.
      Parents, particularly fathers, were rarely present. It was suggested that age
      segregation during adolescence is the result of a lack of contact with relatives.

PMID- 24318199
TI  - Identity status in high school students: Critique and a revised paradigm.
AB  - The validity of applying the Marcia identity status paradigm to study of high
      school students is examined. Uncritical categorization of young adolescents into
      the identity statuses originally validated upon university students raises
      various issues. A revised paradigm for study of identity style among high school
      students is presented. It is suggested that the issues raised-the validity of
      measures for varying age groups and the role of environmental demands-are related
      to the eventual formulation of a life-span conceptualization of identity style. 

PMID- 24318200
TI  - Reciprocity, agreement, and family style in family systems with a disturbed and
      nondisturbed adolescent.
AB  - Doane's recent review of interaction studies of families with disturbed and
      nondisturbed adolescents enumerated a number of conclusions concerning
      relationships and family functioning in families with a disturbed adolescent. The
      present study used a questionnaire approach to test hypotheses based on these
      conclusions, hypotheses which were largely supported in the analyses. When a
      disturbed adolescent was involved, families evidenced less reciprocity of needs,
      had greater disagreement about parents' needs, greater disagreement about family
      related issues, more marital dysfunction, more rigidity and less clarity about
      expectations, and less satisfaction and more anxiety on the part of the
      adolescents. That families with a disturbed adolescent were discriminably
      different from families without a disturbed adolescent is supportive of a family
      systems perspective to family functioning. Speculations of a causal nature are
      offered, with suggestions that future research be designed to take advantage of
      causal analysis procedures. 

PMID- 24318201
TI  - Comparison of adolescents' perceptions and behaviors in single- and two-parent
      families.
AB  - This study investigated the self-concepts, school achievement, occupational
      aspirations, vocational maturity, and perceptions of parents of children from two
      parent and single-parent homes. The sample contained 559 children, 19% from
      single-parent homes. A multivariateF indicated children from two-parent homes had
      significantly higher school grades and occupational aspirations. There were also
      significant differences in children's perceptions of relationships with fathers,
      but not with mothers. It was argued that family structure has an impact on
      adolescents' perceptions and behaviors. 

PMID- 24318202
TI  - Career-marriage orientations in college youth: An analysis of perceived personal
      consequences and normative pressures.
AB  - The present research was designed to examine factors associated with career and
      marriage orientations in male and female college students. The first phase of the
      research identified qualitatively different factors associated with variations in
      life structure. Respondents completed an open-ended questionnaire which elicited
      the perceived consequences and normative pressures concerning three life
      structure alternatives: (a) emphasizing career, (b) emphasizing marriage, and (c)
      placing equal emphasis on career and mariage. A set of 24 concerns was
      identified, and sex differences on several of these dimensions were noted. In
      general, the data were consistent with previous analyses of value structures in
      adults. The second phase of the research used a quantitative approach to examine
      the three life structure alternatives. Males and females did not differ in the
      relative emphasis they intended to give to career and marriage. However, sex
      differences in the perceived consequences of the life structure alternatives were
      noted. 

PMID- 24318203
TI  - Intended childlessness in late adolescence: Personality and psychopathology.
AB  - A series of studies are presented which examine the relation between parenthood
      intentions (intend to be a parent and intend to remain childless) and self
      concept, mental health, and grade point average in a college student population.
      The results suggest that college students not intending to have a child tend to
      be statistically deviant on all the variables examined. Cross-validation results
      suggest a high frequency of psychopathology among the sample of young intended
      nonparent college students. Based on the MMPI results, the intention to be a
      nonparent appears to be associated with general maladjustment, rather than just a
      deviancy from social norms. 

PMID- 24318204
TI  - The role of peer and adult models for drug taking at different stages in
      adolescence.
AB  - Peer and adult models are known to exert strong influences on the initiation of
      adolescent drug use. In this study five hypotheses concerning the role of self
      perceived availability of the two types of models at different times in
      adolescence were tested. The results indicate that maturation is accompanied by
      an increasing perception of adult and peer models for four types of substance
      taking. Furthermore, the correlations between use rates and the number of adult
      and peer models seem systematically influenced by maturation for marijuana and
      pill variables, but are not as clearly changed for different alcohol use
      indicators. The perceived number of peer models is more related to usage rates
      than the perceived number of adult models for girls at all ages. There is
      differential association between self-use and the perceived number of peer and
      adult models only at the high school level for boys. 

PMID- 24318205
TI  - Competition between the RNA 3 molecules of wildtype alfalfa mosaic virus and the
      temperature-sensitive mutant Tbts 7(uv).
AB  - In mixed infections of wildtype (wt) alfalfa mosaic virus (AMV) and a temperature
      sensitive mutant Tbts 7(uv), which carries a thermosensitive defect in the early
      function of the coat protein, the mutant symptoms were not found at 30 degrees C.
      In the progeny from these mixed infections almost no mutant coat protein and no
      mutant RNA 3 could be detected. Even at 23 degrees C there was some loss of
      mutant RNA 3 and coat protein from the progeny of the mixed infections. Analysis
      and comparison of mutant and wt ds RNA preparations revealed a lower ds RNA 3
      content for the mutant preparation at 23 degrees C. Also the amount of RNA 3 in
      virion preparations was lower for the mutant than for wt. These results point to
      a mutation in the RNA 3 of Tbts 7(uv) which diminishes its affinity for the viral
      replicase. 

PMID- 24318206
TI  - Nucleotide homologies between the glycosylated seed storage proteins ofGlycine
      max andPhaseolus vulgaris.
AB  - We have compared the partial nucleotide and derived amino acid sequences of a
      phaseolin seed storage protein gene ofPhaseolus vulgaris (1) and a conglycinin
      storage protein gene ofGlycine max (2). Although these proteins are not
      antigenically related to one another, the architecture of the genes is similar
      throughout the sequences compared here. Intervening sequences interrupt the same
      amino acid positions in both genes. Within the 28% of theG. max gene and the 38%
      of theP. vulgaris gene represented in this comparison, 73% of the nucleotides in
      the coding and intervening sequences are identical, excluding the insertions and
      deletions. The nucleotide mismatches found in the coding sequences are
      distributed throughout the three codon positions with little bias towards the
      third codon position. In addition to the single nucleotide differences, six
      insertions or deletions, ranging from three to twenty-seven nucleotides in
      length, occur in this portion of the coding region and these are partially
      responsible for the molecular weight differences of the conglycinin alpha'
      subunit and the phaseolin subunit. 

PMID- 24318207
TI  - A detailed restriction endonuclease site map of theZea mays plastid genome.
AB  - Fragments produced by partial digestion of plastid DNA fromZea mays withEco RI
      were cloned in Charon 4A. A circular, fine structure physical map of the plastid
      DNA was then constructed from restriction endonucleaseSal I,Pst I,Eco RI, andBam
      HI recognition site maps of cloned overlapping segments of the plastid genome.
      These fragments were assigned molecular weights by reference to size markers from
      both pBR322 and lambda phage DNA. Because of the detail and extent of the derived
      map, it has been possible to construct a coordinate system which has a unique
      zero point and within which all the restriction fragments and previously
      described structural features can be mapped. A computer program was constructed
      which will display in a circular fashion any of the above features using an X-Y
      plotter. 

PMID- 24318208
TI  - Transfer RNA genes ofZea mays chloroplast DNA.
AB  - A minimum of 37 genes corresponding to tRNAs for 17 different amino acids have
      been localized on the restriction endonuclease cleavage site map of theZea mays
      chloroplast DNA molecule. Of these, 14 genes corresponding to tRNAs for 11 amino
      acids are located in the larger of the two single-copy regions which separate the
      two inverted copies of the repeat region. One tRNA gene is in the smaller single
      copy region. Each copy of the large repeated sequence contains, in addition to
      the ribosomal RNA genes, 11 tRNA genes corresponding to tRNAs for 8 amino acids.
      The genes for tRNA2 (Ile) and tRNA(Ala) map in the ribosomal spacer sequence
      separating the 16S and 23S ribosomal RNA genes. The three isoaccepting species
      for the tRNAs(Leu) and the three for tRNAs(Ser), as well as the two isoaccepting
      species for tRNA(Asn), tRNA(Gly), tRNAs(Ile), tRNAs(Met), tRNAs(Thr), are shown
      to be encoded at different loci.Two independent methods have been used for the
      localization of tRNA genes on the physical map of the maize chloroplast DNA
      molecule: (a) cloned chloroplast DNA fragments were hybridized with radioactively
      labelled total 4S RNAs, the hybridized RNAs were then eluted, and identified by
      two-dimensional polyacrylamide gel electrophoresis, and (b) individual tRNAs
      were(32)P-labelledin vitro and hybridized to DNA fragments generated by digestion
      of maize chloroplast DNA with various restriction endonucleases. 

PMID- 24318209
TI  - Non-oncogenic T-region mutants ofAgrobacterium tumefaciens do transfer, T-DNA
      into plant cells.
AB  - A new procedure for site-directed mutagenesis has been applied to the shooting
      and rooting loci of T-DNA of an octopine Ti-plasmid ofAgrobacterium tumefaciens.
      Mutants have been obtained which induced tumours that either developed shoots or
      produced more roots than normally observed. Double mutations, in which both types
      of T-DNA loci were affected, resulted in non-oncogenic strains. Indications have
      been obtained, showing that T-DNA coded oncogenic functions can be eliminated
      without affecting T-DNA transfer into plant cells. 

PMID- 24318210
TI  - Postmastectomy radiation therapy.
AB  - Many women undergo mastectomy as treatment of their breast cancer either because
      of personal preference or because of tumor-related factors making mastectomy the
      preferred surgical option. The use of postmastectomy radiation therapy has been
      shown to decrease the risk of local recurrence and in some cases improve overall
      survival. Decisions regarding the need for postmastectomy radiation therapy can
      be complex and rely on careful review of many factors. Lymph node status, tumor
      size, tumor grade, receptor status, presence or absence of lymphovascular space
      invasion, Her-2/neu status, margin width, and patient age all need to be
      considered when making recommendations for or against postmastectomy radiation
      therapy. In this article, we provide a review of the relevant literature
      pertaining to postmastectomy radiation therapy in order to help guide this
      decision-making process. 

PMID- 24318211
TI  - Mesenteric inflammatory veno-occlusive disease: radiographic and histopathologic
      evaluation of 2 cases.
AB  - Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of
      inflammatory enterocolitis whose clinical and imaging presentation can be
      confused with mesenteric venous thrombosis and inflammatory bowel disease. We
      report two cases of histologically proven MIVOD in patients presenting with
      abdominal pain and describe potentially useful distinguishing features at
      contrast-enhanced CT, including prominent small pericolonic arteries and veins
      but a diminutive or absent inferior mesenteric vein. Alerting referring
      clinicians to the possibility of this diagnosis may help avoid unnecessary
      anticoagulation and reduce diagnostic delay. Treatment of MIVOD is surgical
      resection, which is typically curative. 

PMID- 24318212
TI  - Effect of untreated triangular fibrocartilage complex (TFCC) tears on the
      clinical outcome of conservatively treated distal radius fractures.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of untreated
      triangular fibrocartilage complex (TFCC) tear on the clinical outcome of
      conservatively treated distal radius fractures. MATERIALS AND METHODS: This
      prospective study comprised 47 consecutive patients who presented at our clinic
      between January 2009 and January 2010 with displaced radius distal fracture and
      were treated with closed reduction and casting. During the first 15 days of
      treatment, all patients underwent wrist MR imaging to detect traumatic TFCC
      tears. At the final follow-up, all patients were evaluated with Mayo wrist
      function score and wrist radiographs. Patients were divided into two groups
      according to presence of TFCC tear, and two groups were analyzed statistically.
      RESULTS: The mean follow-up period was 38.9 +/- 3.5 months (range 36-48). TFCC
      tear was detected in 24 cases, and remaining 23 cases had no TFCC tear. Both
      groups were statistically similar regarding age (p = 0.574), gender (p = 0.108),
      dominant side involvement (p = 0.339), fracture type (p = 0.709) and
      immobilization period (p = 0.514). According to Mayo wrist score, excellent
      results were obtained in 21 (44.7%) cases, good in 16 (34.0%) and satisfactory in
      10 (21.3%). No significant difference was observed between groups in wrist
      function scores (p = 0.451). Radiographic measurements were similar between
      groups (radial length p = 0.835, volar til p = 0.464, radial inclination p =
      0.795). CONCLUSIONS: Traumatic TFCC tears which are frequently seen together with
      distal radius fractures do not affect the long-term functional results.
      Therefore, further diagnostic tests and treatment of TFCC tears in patients with
      stable distal radius fractures may be unnecessary. However, it should be borne in
      mind as a reason for continuing wrist pain and instability after distal radius
      fractures despite proper radiologic recovery.

PMID- 24318214
TI  - Biodegradation of endosulfan in broth medium and in soil microcosm by Klebsiella
      sp. M3.
AB  - Nine endosulfan degrading bacterial strains were isolated by soil enrichment with
      endosulfan. Bacterial strain M3 was the most efficient degrader. Endosulfan
      degradation was accompanied by a decrease in pH of the medium and an increase in
      chloride ion concentration. The bacterium was tested for its ability to degrade
      endosulfan at different concentrations in broth and soil. Maximum degradation
      occurred at concentrations of 50 MUg/ml of broth and 100 MUg/g of soil. Values of
      Ks and Vmax were different for (alpha)- and (beta)-endosulfan in broth. The
      kinetic indices (Vmax/Ks) for alpha-endosulfan and beta-endosulfan were 0.051 and
      0.048 day(-1) respectively, indicating that (alpha)-endosulfan was more rapidly
      degraded. Bacterial strain M3 was identified as Klebsiella sp. M3 on the basis of
      16S rDNA sequence similarity (GenBank accession number JX273762).

PMID- 24318213
TI  - A novel role for bioactive lipids in stem cell mobilization during cardiac
      ischemia: new paradigms in thrombosis: novel mediators and biomarkers.
AB  - Despite major advances in pharmacological and reperfusion therapies, regenerating
      and/or replacing the infarcted myocardial tissue is an enormous challenge and
      therefore ischemic heart disease (IHD) remains a major cause of mortality and
      morbidity worldwide. Adult bone marrow is home for a variety of hematopoietic and
      non-hematopoietic stem cells including a small subset of primitive cells that
      carry a promising regenerative potential. It is now well established that
      myocardial ischemia (MI) induces mobilization of bone marrow-derived cells
      including differentiated lineage as well as undifferentiated stem cells. While
      the numbers of stem cells carrying pluripotent features among the mobilized stem
      cells is small, their regenerative capacity appears immense. Therapies aimed at
      selective mobilization of these pluripotent stem cells during myocardial ischemia
      have a promising potential to regenerate the injured myocardium. Emerging
      evidence suggest that bioactive sphingolipids such as sphingosine-1-phosphate and
      ceramide-1-phosphate hold a great promise in selective mobilization of
      pluripotent stem cells to the infarcted region during MI. This review highlights
      the recent advances in the mechanisms of stem cell mobilization and provides
      newer evidence in support of bioactive lipids as potential therapeutic agents in
      the treatment of ischemic heart disease.

PMID- 24318217
TI  - Design of the Army Study to Assess Risk and Resilience in Servicemembers (Army
      STARRS).
AB  - The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a
      multi-component epidemiological and neurobiological study designed to generate
      actionable evidence-based recommendations to reduce US Army suicides and increase
      basic knowledge about the determinants of suicidality. This report presents an
      overview of the designs of the six components of the Army STARRS. These include:
      an integrated analysis of the Historical Administrative Data Study (HADS)
      designed to provide data on significant administrative predictors of suicides
      among the more than 1.6 million soldiers on active duty in 2004-2009;
      retrospective case-control studies of suicide attempts and fatalities; separate
      large-scale cross-sectional studies of new soldiers (i.e. those just beginning
      Basic Combat Training [BCT], who completed self-administered questionnaires
      [SAQs] and neurocognitive tests and provided blood samples) and soldiers
      exclusive of those in BCT (who completed SAQs); a pre-post deployment study of
      soldiers in three Brigade Combat Teams about to deploy to Afghanistan (who
      completed SAQs and provided blood samples) followed multiple times after
      returning from deployment; and a platform for following up Army STARRS
      participants who have returned to civilian life. Department of Defense/Army
      administrative data records are linked with SAQ data to examine prospective
      associations between self-reports and subsequent suicidality. The presentation
      closes with a discussion of the methodological advantages of cross-component
      coordination.

PMID- 24318218
TI  - Response bias, weighting adjustments, and design effects in the Army Study to
      Assess Risk and Resilience in Servicemembers (Army STARRS).
AB  - The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a
      multi-component epidemiological and neurobiological study designed to generate
      actionable recommendations to reduce US Army suicides and increase knowledge
      about determinants of suicidality. Three Army STARRS component studies are large
      scale surveys: one of new soldiers prior to beginning Basic Combat Training (BCT;
      n = 50,765 completed self-administered questionnaires); another of other soldiers
      exclusive of those in BCT (n = 35,372); and a third of three Brigade Combat Teams
      about to deploy to Afghanistan who are being followed multiple times after
      returning from deployment (n = 9421). Although the response rates in these
      surveys are quite good (72.0-90.8%), questions can be raised about sample biases
      in estimating prevalence of mental disorders and suicidality, the main outcomes
      of the surveys based on evidence that people in the general population with
      mental disorders are under-represented in community surveys. This paper presents
      the results of analyses designed to determine whether such bias exists in the
      Army STARRS surveys and, if so, to develop weights to correct for these biases.
      Data are also presented on sample inefficiencies introduced by weighting and
      sample clustering and on analyses of the trade-off between bias and efficiency in
      weight trimming.

PMID- 24318222
TI  - Rate of release of spruce budworm pheromone from virgin females and synthetic
      lures.
AB  - The rate of pheromone [(E)- and (Z)-11-tetradecenal] release from calling
      virginChoristoneura fumiferana females and synthetic lures was determined in both
      static and aerated atmospheres. In a static system ca. 2 ng/hr was recovered per
      female. Owing to the > 75% adsorption onto the females' bodies in static
      atmospheres, the actual release rate has to be corrected to roughly 9-27 ng/hr,
      depending on the percentage adsorbed. In the air-flow system, females were found
      to release between 4 and 20 ng/hr. On a 16?8 light-dark cycle, calling began 1-2
      hr before lights-off and continued nonstop until lights-on. Pheromone was emitted
      throughout calling, while no pheromone was detected during the noncalling
      periods. 

PMID- 24318221
TI  - Improved outcomes in adjuvant radiotherapy for oral cavity carcinoma at an
      academic center: a matched-pair analysis.
AB  - OBJECTIVES/HYPOTHESIS: Our objective was to evaluate for outcomes differences for
      patients with oral cavity squamous cell carcinoma (OCSCC) who underwent primary
      surgical resection at an academic center (AC), followed by postoperative
      radiation therapy either at the AC or at a nonacademic radiation treatment center
      (non-AC). DESIGN: Secondary analysis of a retrospective cohort of patients with
      previously untreated upper aerodigestive tract SCC who underwent surgery followed
      by adjuvant therapy at an AC from 2002 to 2012. Fifty-three matched pairs of
      OCSCC patients surgically treated at the AC, but receiving adjuvant radiation at
      either an AC or a non-AC, were evaluated for differences in clinicopathologic
      variables, radiation treatment metrics, and survival outcomes. The main outcome
      measures were overall survival, disease-specific survival, and locoregional
      control rates. RESULTS: Matched pairs were closely comparable in TNM (tumor,
      node, metastasis) stage, age, and gender. There were no significant between
      groups differences in demographic and clinicopathologic variables except for
      smoking status (never smokers 43.3% for AC vs. 20.8% for non-AC; P=0.037). Non-AC
      OCSCC patients received a significantly lower total radiation dose (P=0.0004) and
      lower radiation fractional dose (P=0.0002) than their AC matched-pair
      counterparts. AC treatment was associated with improved overall survival
      (P=0.005), disease-specific survival (P=0.019), and locoregional control
      (P=0.016). AC treatment was an independent predictor of overall survival on
      multivariate analysis (P=0.044), after adjustment for clinicopathologic
      differences between groups. CONCLUSIONS: Improved survival for combined modality
      treatment of OCSCC at the AC was noted on multivariate analysis. Differences in
      key radiation treatment metrics could explain survival differences noted in this
      study. LEVEL OF EVIDENCE: 4.

PMID- 24318219
TI  - Clinical reappraisal of the Composite International Diagnostic Interview
      Screening Scales (CIDI-SC) in the Army Study to Assess Risk and Resilience in
      Servicemembers (Army STARRS).
AB  - A clinical reappraisal study was carried out in conjunction with the Army Study
      to Assess Risk and Resilience in Servicemembers (Army STARRS) All-Army Study
      (AAS) to evaluate concordance of the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV) diagnoses based on the Composite International
      Diagnostic Interview Screening Scales (CIDI-SC) and post-traumatic stress
      disorder (PTSD) checklist (PCL) with diagnoses based on independent clinical
      reappraisal interviews (Structured Clinical Interview for DSM-IV [SCID]).
      Diagnoses included: lifetime mania/hypomania, panic disorder, and intermittent
      explosive disorder; six-month adult attention-deficit/hyperactivity disorder; and
      30-day major depressive episode, generalized anxiety disorder, PTSD, and
      substance (alcohol or drug) use disorder (abuse or dependence). The sample (n =
      460) was weighted for over-sampling CIDI-SC/PCL screened positives. Diagnostic
      thresholds were set to equalize false positives and false negatives. Good
      individual-level concordance was found between CIDI-SC/PCL and SCID diagnoses at
      these thresholds (area under curve [AUC] = 0.69-0.79). AUC was considerably
      higher for continuous than dichotomous screening scale scores (AUC = 0.80-0.90),
      arguing for substantive analyses using not only dichotomous case designations but
      also continuous measures of predicted probabilities of clinical diagnoses.

PMID- 24318223
TI  - Role of (Z)- and (E)-11-tetradecenyl acetate pheromone components in the sexual
      behavior of the (Z) strain of the european corn borer,Ostrinia nubilalis
      (Lepidoptera: Pyralidae).
AB  - A glass tube olfactometer bioassay was used to examine pheromone response of
      males of the (Z)-pheromone strain ofOstrinia nubilalis (Hubner). The presence of
      (E)-11-tetradecenyl acetate at the natural ratio to (Z)-11-tetradecenyl acetate
      (97?3; Z?E) did not consistently elevate wing-fanning, upwind walking, or clasper
      extrusion over (Z)-11-tetradecenyl acetate alone. This bioassay did not reveal
      the behavioral role of (E)-11-tetradecenyl acetate. 

PMID- 24318224
TI  - Effect of pheromone concentration on organization of preflight behaviors of the
      male gypsy moth,Lymantria dispar(L.).
AB  - Male gypsy moths (Lymantria dispar L.) in a wind tunnel at 24 degrees  respond to
      decreasing dosages (1 MUg to 0.1 pg) of (+)-cis-7,8-epoxy-2-methyloctadecane with
      a decrease in probability of wing-fanning, an increase in wing-fanning latency,
      and an increase in the number of behaviors (body jerks, antennal twitches, steps,
      and wing tremors) preceding fanning. Males initiating any behavior prior to wing
      fanning had a 70% probability of wing-fanning and 97% of the males that wing
      fanned eventually flew. The sequence of behaviors from quiescence to flight is
      not organized in a hierarchy, as this concept is used in ethology, nor is it
      dependent upon the concentration of pheromone. The time-average threshold
      concentration of pheromone for response of ca. 90% or more quiescent males is ca.
      1.9 * 10(-17) g/cm(3) over < 0.3 min. 

PMID- 24318225
TI  - Mate location strategies of gypsy moths in dense populations.
AB  - In high-density populations, the male gypsy moth (Lymantria dispar) "appetitive"
      flight is primarily vertical and within 1-50 cm of tree boles. Preceding location
      of a female, males land on trees or occasionally tree foliage and walk while wing
      fanning. In high-density populations females may mate before calling, often prior
      to wing expansion or hardening. Additional matings may occur before any or full
      deposition of egg masses. Virgin females are not coy, whether their wings are
      unexpanded, or hardened and held rooflike, or whether they are calling or not.
      They generally mate with the first willing male and do not exercise sexual
      selection by an acceptance or rejection reaction. The mating structure in dense
      populations would seem to reduce selective pressure for female emission of and
      direct male anemotactic flight to attractant pheromone. A low proportion of males
      "search" appropriate objects, especially tree trunks, in the walking-wing-fanning
      state. Such males often are successful in locating virgin females before calling
      commences. This male strategy presumably would not be successful in low
      population densities. 

PMID- 24318226
TI  - Effect of allyl isothiocyanate on field behavior of crucifer-feeding flea beetles
      (Coleoptera: Chrysomelidae).
AB  - When water traps baited with allyl isothiocyanate (AIC)diffusing through
      polyvinyl chloride (PVC) and rubber membranes were used to monitor four species
      of crucifer-feeding flea beetle adults in a rutabaga field at L'Assomption, Que.
      in 1980-1981, differential responses to AIC were observed.Phyllotreta cruciferae
      was more attracted to AIC thanP. striolata, whereas the behavior ofPsylliodes
      punctulata was not affected by the presence of AIC. The traps with the PVC
      membrane caught significantly more flea beetles than the traps with the rubber
      membrane in 1980, but caught a similar number in 1981. Sticky traps covered with
      AIC mixed with Tangletrap(r) caught significantly more flea beetles than control
      sticky traps. 

PMID- 24318227
TI  - Defensive secretion of the pill millipedeGlomeric marginata : I. Fluid production
      and storage.
AB  - AdultGlomeris marginata reloaded glandular defensive fluid slowly and fairly
      constantly at 15  degrees C for 100 days after being milked to depletion. Female
      millipedes produced more sticky exudate than males, but the two sexes stored
      secretion at approximately the same absolute rate, 12 MUg/individual/day. Hence,
      males, which weighed one third as much as females, accumulated disproportionately
      more secretion. MaleGlomeris in the reloading treatments after 75 days yielded as
      much exudate as controls, millipedes given 100 days to supplement their field
      reserves, whereas experimental females always produced less secretion than
      controls. Projections from these data suggest that adultGlomeris, regardless of
      sex, require more than 4 months to replenish their defensive reserves after
      completely discharging them in an attack. 

PMID- 24318228
TI  - Filbertworm sex pheromone : Identification and field tests of (E,E)- and (E,Z)
      8,10-dodecadien-1-ol acetates.
AB  - (E,E)- and (E,Z)-8,10-Dodecadien-1-ol acetates were identified in a 1?4.3 ratio
      in the extract of abdominal tips of female filbert-worm moths,Melissopus
      latiferreanus (Walsingham). The identifications were based on electroantennogram
      (EAG) analysis, gas chromatography, mass spectrometry, ozonolysis, and synthesis.
      TheE,Z isomer produced the stronger EAG response. In the field tests of various
      ratios ofE,E?E,Z, the ratio found in the extract captured the most males. The
      pureE,E isomer initially was not attractive by itself (<0.1%E,Z) but became
      attractive after a few days, presumably because of isomerization. TheE, Z isomer
      (<0.1%E,E) was attractive initially, but this compound might have isomerized
      faster than theE,E isomer. A study of the isomerization showed that regardless of
      the initial mixture of 8,10-dodecadien-1-ol acetate isomers, almost complete
      equilibration existed after one month. The equilibrium mixture consisted of
      9%Z8,E10, 65%E8,E10, 23%E8,Z10, and 3%Z8,Z10. Concentrations in rubber septa (1?4
      ratio ofE,E toE,Z) of 0.03-3.0 mg/septum produced equivalent trap catches. 

PMID- 24318229
TI  - Concentration and preliminary characterization of a chemical attractant of the
      oyster drill,Urosalpinx cinerea.
AB  - Predatory muricid gastropods,Urosalpinx cinerea, respond to specific chemical
      stimuli by creeping upcurrent. Attractant substances originate from living
      barnacles. Newly hatched snails have no prior predatory experience but respond
      strongly to attractants. We report here methods for rapidly extracting and
      desalting attractants from seawater. Attractants from living barnacles are
      relatively large, at least partially proteinaceous, heat-stable molecules (> 1000
      but < 10000 dallons) that adsorb onto Amberlite XAD-7, a polyacrylate water
      purification resin, at neutral pH. Attractants remain adsorbed to the resin
      during a wash with deionized water and can be eluted in a small volume with 100%
      methanol. Attractant substances are effective in the bioassay in MUg/liter
      concentrations (octa- to nanomolar range). Potency is destroyed by nonspecific
      proteases (carboxy-peptidase and pronase) but not by trypsin. Attractant is not
      sequestered within barnacles. 

PMID- 24318230
TI  - Toxicity of nitro compounds fromLotus pedunculatus to grass grub (Costelytra
      zealandica) (Coleoptera: Scarabaeidae).
AB  - Crude extracts of root of the forage legumesLotus pedunculatus andCoronilla varia
      (crownvetch) were toxic when administered orally to 3rd instarCostelytra
      zealandica larvae. A group of 3-nitropropanoyl-D-glucopyranoses was isolated from
      active fractions of the crude extracts. These toxins, some of which were already
      known fromC. varia, have not previously been reported fromL. pedunculatus. The
      compounds were present in root tissue of this species at a concentration of about
      1% dry weight. They include the triester karakin and the diesters coronarian and
      cibarian, all of which were toxic to larvae ofC. zealandica at levels which could
      account fully for the activity of the crude extracts. 

PMID- 24318231
TI  - Occurrence of sex attractant pheromone, 2,6-dichlorophenol, in relation to age
      and feeding in American dog tick,Dermacentor variabilis (say) (Acari:Ixodidae).
AB  - No detectable sex pheromone, 2,6-dichlorophenol (2,6-DCP), was found
      inDermacentor variabilis engorged nymphs, teneral females, replete females, or
      unfed males. The amount of 2,6-DCP present in unfed females of different ages was
      extremely variable; no relationship between age and 2,6-DCP content in these
      unfed females was observed. Partially fed virgin females had less 2,6-DCP than
      unfed females, but there was no change in pheromone content during the course of
      feeding. Sex pheromone was also found in partially fed males. 

PMID- 24318232
TI  - Aqueous extracts from indigenous plants as oviposition deterrents forHeliothis
      virescens (F.).
AB  - In laboratory and field tests, water extracts from plant foliage deterred
      oviposition byHeliothis virescens (F.). A maximum reduction of 93% was attained
      in laboratory oviposition cages. When females were allowed free choice of treated
      or untreated tobacco plants in field cage and field tests, maximum reductions in
      oviposition were 71 and 83%, respectively. 

PMID- 24318233
TI  - Berberine: A naturally occurring phototoxic alkaloid.
AB  - The isoquinoline alkaloid berberine, present in nine different plant families was
      found to be phototoxic to mosquito larvae. In the presence of near UV the LC50
      for acute 24-hr toxicity was 8.8 ppm compared to 250 ppm for dark controls.
      Mosquito larvae that were treated with 10 ppm berberine plus near UV for 24 hr
      and then transferred to berberine-free water showed decreased larval survival and
      resulted in a smaller cumulative number of pupae and adults as compared to
      controls, during a subsequent 4-week development period. Berberine was found to
      be a singlet O2 generator in experiments with the chemical trap 2,5-dimethyl
      furan. A slight increase in chromosome aberrations in Chinese hamster cells was
      also observed with berberine plus near UV treatment. The significance of the
      phototoxicity of berberine is discussed in relation to plant-insect relations. 

PMID- 24318234
TI  - Attraction of male spruce budworm moths,Choristoneura fumiferana (Clemens), to
      pheromone-baited traps in small-tree thinnings.
AB  - Mean catches of spruce budworm,Choristoneura fumiferana (Clemens), moths were not
      significantly different among four small-tree thinning treatments of young spruce
      fir-hemlock regeneration. Significant inverse relationships were found between
      trap catches and distances to nearby spruce-fir-hemlock overstory. Prevailing
      wind directions indicated that moths were attracted anemotactically to upwind
      pheromone sources. No definite trends were detected between catches and
      temperature or precipitation. 

PMID- 24318235
TI  - New sex attractants for 35 tortricid and 4 other lepidopterous species, found by
      systematic field screening in the Netherlands.
AB  - Most of the known sex attractants and pheromones found for Tortricidae attract
      species of the subfamily Tortricinae. In order to find more sex attractants for
      species of the subfamily Olethreutinae, about 60 one- and two-component lures
      were screened for attractancy in different biotopes in the Netherlands. Most of
      the chemicals tested were straight-chain dodecen-1-ols and their acetates. The
      species captured belonged to the following families and subfamilies: Tortricinae
      (5), Olethreutinae (30), Noctuidae (2), Gelechiidae (1), Gracillariidae (1). Some
      of the species captured are recorded as pest species in forestry:Epinotia
      tedella, Gypsonoma aceriana, Cydia strobilella, C. zebeana, Petrova resinella,
      Blastesthia turionella, andB. posticana. 

PMID- 24318236
TI  - Structure-activity relationship of unsaturated fatty acids as mosquito
      ovipositional repellents.
AB  - Various straight-chain unsaturated fatty acids from C14 to C24 were evaluated for
      their ovipositional repellency against gravid females of the southern house
      mosquitoCulex quinquefasciatus Say, and the relationship between the structures
      of the fatty acids and their ovipositional repellency was determined. A double
      bond withZ configuration was prerequisite for an unsaturated fatty acid to be
      highly repellent;E isomers were less active or even inactive. No relationship was
      found between the repellency and the number of double bonds in the unsaturated
      fatty acids. In C18 monounsaturated fatty acids, (Z)-9 acid was more active than
      (Z)-11 and (Z)-6 acids, indicating that a double bond at the 9 position rendered
      an acid highly repellent. Among (Z)-9-alkenoic acids of different chain lengths,
      the most repellent was C18 acid which was also more active than (Z)-11-C20, (Z)
      13-C22, and (Z)-15-C24 acids. Oleic[(Z)-9-octadecenoic]acid, which met all these
      criteria, was the most ovipositionally repellent among the unsaturated fatty
      acids tested. 

PMID- 24318237
TI  - Sex pheromone of a conifer-feeding budworm,Choristoneura retiniana, Walsingham.
AB  - Sex pheromone components collected from femaleChristoneura retiniana included 11
      tetradecenyl acetates and alcohols. The major component wasE-11-tetradecenyl
      acetate (E11-14?Ac) with a lesser amount ofZ isomer necessary to induce male
      response. A 92?8 ratio ofE,Z11-14? Ac appeared optimal. The alcohol component was
      present at about 10% of the total pheromone mixture, and traps baited with
      acetates plus alcohol surpassed unmated females in their degree of
      attractiveness. Chemical analysis indicated a 9?:1 ratio of theE - Z isomers of
      11-tetradecenyl alcohol (11-14?ol) pheromone components, although bait
      formulations containing a predominance of either theE orZ isomers were equally
      successful in field bioassays. Based on male response to traps,E- andZ11-14?Ac
      (92?8E - Z) are essential pheromone components for long-range sex attraction. The
      11-14? ol enhanced attraction when added at 10% of the total pheromone blend. 

PMID- 24318238
TI  - Interactions of temperature and ferulic acid stress on grain sorghum and
      soybeans.
AB  - Experiments were conducted to test the hypothesis that alleiopathic effects of
      ferulic acid (FA) may be altered by the temperature conditions of the growth
      environment. Growth of grain sorghum and soybean seedlings over a 10-day
      treatment period showed that a significant interaction effect occurred between
      environmental temperatures and FA treatments. Sorghum grown with an average day
      temperature of 37  degrees C and soybeans grown at 34  degrees C had greater dry
      weight reductions caused by FA than when the respective environments were 8 
      degrees C and 11  degrees C lower. The threshold concentration for inhibition of
      sorghum growth was 0.2 mM FA under the hot conditions and 0.4 mM FA with the
      cooler conditions. Soybeans were more sensitive than sorghum, and these
      inhibition thresholds for the hot and cool environments were 0.1 and 0.25 mM FA.
      These results demonstrate that temperature stress enhances allelochemical
      inhibition and indicate that interactions with the environment are an important
      consideration for understanding allelopathy. 

PMID- 24318239
TI  - Demonstration of sex pheromones in caddisflies (Trichoptera).
AB  - Field tests with live, caged females and whole-body extracts of females of the
      caddisflyGumaga griseola (McLachlan) (Trichoptera: Sericostomatidae) demonstrate,
      for the first time, the existence of a chemically mediated sexual communication
      system in this insect order. Both live females and extracts are significantly
      more attractive to conspecific males than either empty control traps or traps
      baited withGumaga nigricula (McLachlan) females. Anatomical structures suggest
      that semiochemicals are widespread in Trichoptera. 

PMID- 24318240
TI  - Response of the clerid predatorThanasimus dubius (F.) to bark beetle pheromones
      and tree volatiles in a wind tunnel.
AB  - Tree volatiles and pheromones produced by southern bark beetles were bioassayed
      for response by the clerid predatorThanasimus dubius (F.). Upwind flights in a
      laboratory olfactometer, modified from Visser (1976), were used to determine the
      attractiveness of compounds. Differences in response to a solvent control and
      pheromone treatment were tested for statistical significance using the Wilcoxon
      signed ranks test. Both sexes ofT. dubius responded to frontalin, ipsdienol, and
      alpha-pinene in a dose-dependent manner with different but overlapping
      concentration ranges. Strong differences between the sexes were observed in
      response totrans-verbenol, verbenone, andl-beta-pinene. Neither sex responded to
      ipsenol orendo-brevicomin. 

PMID- 24318241
TI  - Measurements of cytochrome f and P-700 in intact leaves of Sinapis alba grown
      under high-light and low-light conditions.
AB  - The oxidation and reduction of cytochrome f and P-700 is measured
      spectrophotometrically in leaves of low-light and high-light plants. After
      illumination with red light, an induction phenomenon for cytochrome f oxidation
      is observed which indicates a regulation of photosystem I activity through energy
      distribution between the pigment systems by the energy state of the membrane.
      After far-red excitation the reduction of cytochrome f in the dark is much slower
      in low-light leaves. This shows that cyclic electron transport is not improved in
      low-light plants under these conditions. P-700 is oxidized on excitation with far
      red light. However, with high intensities of far-red light, P-700 is partially
      reduced again which is due to a low extent of photosystem II excitation with the
      far-red used in the experiments. The low-light leaves show greater sensitivity of
      photosystem II to this excitation. The initial rate of the cytochrome f oxidation
      rate is the same in low-light and high-light leaves. This shows that several P
      700 are connected with only one electron transport chain. The consequences of
      these results concerning the tripartite concept and the photosynthetic unit are
      discussed. In the high-light plants the experimental data can be well explained
      by the tripartite organization of the photosynthetic unit. In low-light plants,
      however, a multipartite organization has to be postulated. In the partition
      regions of the grana, several antennae systems I, antennae systems II, and light
      harvesting complexes can communicate with one electron transport chain. 

PMID- 24318242
TI  - Cation-activated ATPase activity of plasmalemma-enriched membrane preparations
      from maize coleoptiles.
AB  - The ATPase activity present in plasmalemma-enriched preparations from maize
      coleoptiles shows an optimum at pH 6, a strong dependence on Mg(2+), and is
      stimulated by K(+) and other monovalent cations, both organic and inorganic. The
      activation of ATPase by K(+) obeys Michaelis Menten kinetics, saturation being
      reached at 50 mM K(+) concentration. K(+), Mg(2+)-stimulated ATPase activity is
      strongly inhibited by N,N'-dicyclohexylcarbodiimide and by diethylstilbestrol
      and, to a lesser extent, by octylguanidine. 

PMID- 24318243
TI  - Transport of proteins from cytoplasm into plastids in chloramphenicol-treated
      bean leaf discs : Autoradiographic evidence.
AB  - Leaf discs from etiolated bean plants were found to incorporate [(3)H]lysine into
      80 S ribosomesynthesized proteins in the presence of chloramphenicol (100 mg l(
      1)) when exposed to light. After a 7 min pulse of [(3)H]lysine, the discs were
      transferred to the same medium but with nonradioactive lysine, and postincubation
      was carried out for 24 h. The number of silver grains over the plastids, after
      the first period of a lag phase, indicates a large increase between 12 and 24 h
      of postincubation. Simultaneously, the labeling of the cytoplasm becomes reduced
      during that period. The results show that during inhibition of the protein
      formation within plastids, the synthesis of plastid-destined proteins in
      cytoplasm, as well as their transport into plastids, can still proceed. 

PMID- 24318244
TI  - Composition of soluble cuticular lipids and water permeability of cuticular
      membranes from Citrus leaves.
AB  - Water permeability and composition of soluble cuticular lipids of isolated
      cuticular membranes from leaves of Citrus aurantium L. were investigated for 3
      successive years. The average water permeability coefficient determined using 169
      cuticular membranes was 1.09.10(-7) cm s(-1) with a standard deviation of
      0.78.10(-7) cm s(-1). There were no significant differences in water permeability
      between years. Cuticular membranes are characterized by a great variability in
      water permeability both within and between years. Both water permeability of
      individual membranes and variability between membranes are shown to be determined
      by soluble cuticular lipids contained within the cuticular membranes. The soluble
      cuticular lipids of Citrus leaves are composed of fatty acids, primary alcohols,
      esters, and hydrocarbons. They occur in amounts of 9.84 MUg cm(-2), which
      represents approx. 3% of the total mass of isolated cuticular membranes. The
      specific weight of cuticular membranes (365.4 MUg cm(-1)) and total amount of
      soluble cuticular lipids did not vary significantly between years. Significant
      differences were observed for the amounts and composition of the constituent
      classes of lipids. Six homologues comprise 86% of the fatty acids (C16; C18; C19;
      C21; C24; C26), 83% of the primary alcohols (C24; C26; C28; C30; C32; C34) and
      88% of the esters (C36; C38; C40; C41; C42; C44). Eleven major homologues amount
      only to 62% of the total hydrocarbons (C16; C17; C18; C20; C26; C27; C29; C30;
      C31; C32; C33). Variability in the composition of soluble cuticular lipids
      between years was much smaller than variability of water permeability and,
      therefore, no relation between composition of soluble cuticular lipids and water
      permeability could be found. It is suggested that this may be due to the fact
      that the lipid composition observed represents the averages of 20 to 30 membranes
      analyzed so that differences between individual membranes may have been leveled
      out. 

PMID- 24318245
TI  - Endogenous and exogenous auxin in the control of root growth.
AB  - The endogenous indol-3yl-acetic acid (IAA) of detipped apical segments from roots
      of maize (cv ORLA) was greatly reduced by an exodiffusion technique which
      depended upon the preferential acropetal transport of the phytohormone into
      buffered agar. When IAA was applied to the basal cut ends of freshly prepared
      root segments only growth inhibitions were demonstrable but after the endogenous
      auxin concentration had been reduced by the exodiffusion technique it became
      possible to stimulate growth by IAA application. The implications of the
      interaction between exogenous and endogenous IAA in the control of root segment
      growth are discussed with special reference to the role of endogenous IAA in the
      regulation of root growth and geotropism. 

PMID- 24318246
TI  - Studies on flower longevity in Digitalis : Pollination induced corolla abscission
      in Digitalis flowers.
AB  - Flower lifespan was terminated by corolla abscission 5-6 days after stigma
      opening in the unpollinated flower. Increased pollen loads produced increased
      seed set and reduced flower longevity progressively to a minimum of one day after
      pollination with pure pollen. Weakening of the abscission zone was detectable 8 h
      after pollination, whilst the pollen tubes were still within the stigmatic zone,
      suggesting that a stimulus, moving at 4 mm h(-1) minimum, was transmitted through
      the style and ovary. Soon after pollination removal of the stigma prevented the
      pollination-induced corolla abscission. Later it was necessary to remove the
      stigma and upper style, and later still the whole style to delay abscission. The
      progressive induction of the stigma and style took place at a rate of 1.5 mm h(
      1), in advance of the pollen tubes which grew at 0.75 mm h(-1). It was not
      possible to reproduce the pollination effects by application of indoleacetic acid
      (IAA) to the stigma or the style. 

PMID- 24318247
TI  - Phytochrome-mediated germination control of maize caryopses.
AB  - Maize caryopses sown in water germinate equally well either in darkness or under
      any light regime. However, when they are imbibed in mannitol solutions,
      continuous far-red light proves to be strongly inhibitory on the final
      germination as compared to darkness. Similar but less pronounced inhibition is
      also exhibited by continuous red or blue light. Intermittent far-red light can
      partially substitute for continuous far-red light in inhibiting maize caryopsis
      germination, and its effect is reversed to the intermittent red light level when
      red light is given immediately after each far-red illumination. These results are
      interpreted as a proof of existence and involvement of phytochrome in the
      germination control of maize caryopses, though its manifestation is realized only
      under osmotic stress. 

PMID- 24318248
TI  - Occurrence and bioassay responses of G : A plant growth regulator in Eucalyptus
      and other Myrtaceae.
AB  - A growth regulator (G) occurs at high concentrations in adult leaves of E.
      grandis Maiden. Low concentrations of G are present in juvenile leaves of this
      species and also in adult leaves of some other Myrtaceae. Low concentrations of G
      (5*10(-6) and 10(-5) M) promote rooting in mung-bean cuttings and elongation in
      Avena coleoptile sections; high concentrations (5*10(-4) M) inhibit. These and
      other bioassay results indicate that G may have auxin-like activity. 

PMID- 24318249
TI  - Influence of photoperiod on seed development in the genetic line of peas G2 and
      its relation to changes in endogenous gibberellins measured by combined gas
      chromatography - Mass spectrometry.
AB  - When apical senescence in the genetic line of peas G2 was prevented by short days
      fruit development was also found to be retarded. The levels of GA20 and GA29 in
      cotyledons and pods grown under long or short days were measured by gas
      chromatography - mass spectrometry multiple ion monitoring using extracts
      derivatised with deuterated trimethylsilyl groups as internal standards. The
      levels of GA20 but not GA29, were increased by short days. Conventional gas
      chromatography - mass spectrometry showed that relative to GA29 the levels of
      GA19, the other GA identified in G2 cotyledons, were also increased in short
      days. The levels of GA20 in the pods were highest during the main phase of pod
      growth early in fruit development. 

PMID- 24318250
TI  - Regulation of induction of phenylalanine ammonia-lyase in suspension cultures of
      Phaseolus vulgaris.
AB  - Total RNA was extracted from fast growing suspension cells of bean, the mRNA was
      translated and the products of protein synthesis analysed by gel electrophoresis.
      Actinomycin D (20 MUg ml(-1)) added to the cultures 12 h before the induction of
      phenylalanine ammonia-lyase (PAL) activity by naphthylacetic acid (NAA) (1 mg/l)
      and kinetin (0.2 mg/l) failed to prevent the increased activity of the enzyme
      usually produced by this ratio of the plant growth hormones. PAL was isolated and
      purified from suspension cultured bean cells. The purified enzyme ran as a single
      band on polyacrylamide gel electrophoresis. The protein translated from RNA
      prepared from induced and non-induced cells was separated by gel electrophoresis
      and the bands of protein on the gels were compared. There was no evidence for an
      increase in the amount of PAL synthesised in vitro from the mRNA of induced cells
      even though these had 5 times the amount of activity of the enzyme compared with
      that of the non-induced cells. The results indicate that the induction of PAL
      activity is not immediately preceeded by an increase in the synthesis of PAL-mRNA
      by the cells. The control of the activity of the enzyme is discussed with respect
      to this finding. 

PMID- 24318251
TI  - Carbon isotope composition of intermediates of the starch-malate sequence and
      level of the crassulacean acid metabolism in leaves of Kalanchoe blossfeldiana
      Tom Thumb.
AB  - Isotype analyses were performed on biochemical fractions isolated from leaves of
      Kalanchoe blossfeldiana Tom Thumb. during aging under long days or short days.
      Irrespective of the age or photoperiodic conditions, the intermediates of the
      starch-malate sequence (starch, phosphorylated compounds and organic acids) have
      a level of (13)C higher than that of soluble sugars, cellulose and hemicellulose.
      In short days, the activity of the crassulacean acid metabolism pathway is
      predominant as compared to that of C3 pathway: leaves accumulate organic acids,
      rich in (13)C. In long days, the activity of the crassulacean acid metabolism
      pathway increases as the leaves age, remaining, however, relatively low as
      compared to that of C3 pathway: leaves accumulate soluble sugars, poor in (13)C.
      After photoperiodic change (long days->short days), isotopic modifications of
      starch and organic acids suggest evidence for a lag phase in the establishment of
      the crassulacean acid metabolism pathway specific to short days. The relative
      proportions of carbon from a C3-origin (RuBPC acitivity as strong discriminating
      step, isotope discrimination in vivo=200/00) or C4-origin (PEPC activity as weak
      discriminating step, isotope discrimination in vivo=40/00) present in the
      biochemical fractions were calculated from their delta(13)C values. Under long
      days, 30 to 70% versus 80 to 100% under short days, of the carbon of the
      intermediates linked to the starch-malate sequence, or CAM pathway (starch,
      phosphorylated compounds and organic acids), have a C4-origin. Products connected
      to the C3 pathway (free sugars, cellulose, hemicellulose) have 0 to 50% of their
      carbon, arising from reuptake of the C4 from malate, under long days versus 30 to
      70% under short days. 

PMID- 24318252
TI  - Phenylalanine ammonia-lyase levels in protoplasts isolated from hypersensitive
      tobacco pre-infected with tobacco mosaic virus.
AB  - Leaves of tobacco varieties carrying the N gene for hypersensitiviy react to
      tobacco mosaic virus (TMV) infection by forming necrotic lesions and by
      localizing the virus in the vicinity of these lesions. These changes are
      accompanied in the host by an increased metabolic activity, in particular by an
      increased production of phenolic compounds derived from phenylalanine.
      Necrogenesis apparently destroys cells which have become heavily infected despite
      this strong defense reaction. However, it has been demonstrated previously
      (Otsuki et al., 1972) that protoplasts derived from leaves which normally respond
      in vivo to virus inoculation by forming necrotic local lesions, show no such
      response when inoculated in vitro. In the present study we have investigated the
      effect of pre-infecting hypersensitive leaves with TMV on the production or the
      non-production of the factor(s) of necrosis at the level of either protoplasts or
      mesophyll cells isolated from these preinfected leaves. Phenylalanine ammonia
      lyase (PAL), whose rate of synthesis has been shown (Duchesne et al., 1977) to
      increase in stimulated cells of infected leaves, was used as a biochemical marker
      in the search for the stimulus preceding necrogenesis. We found that this
      stimulus concerning PAL activity was never elicited in either protoplasts or
      mesophyll cells which were prepared just before the appearance of necrotic local
      lesions. This result did not depend on the conditions of pre-infection or on the
      methods used to isolate the protoplasts or mesophyll cells. We also assayed
      samples derived from pre-infected leaves that were already carrying local
      lesions, i.e., in which the stimulus and necrogenesis were already operating: not
      only did the isolated protoplasts and mesophyll cells not sustain the stimulus
      concerning PAL activity, but the stimulated enzyme activity decreased abruptly
      and, in most of the experiments, had disappeared within the time necessary for
      maceration. Evidence is presented showing that the non-elicitation or the abrupt
      decrease of stimulated PAL activity could not result from a selection of
      unstimulated cells or from a preferential destruction of stimulated cells during
      maceration of the leaves.Our results support the view that hypertonic osmotic
      pressure is responsible for the non-occurence of the hypersensitive response by
      acting according to one or both of the following processes: it suppresses the
      contacts through plasmodesmata between neighboring cells and, hence, it also
      suppresses the cell-to-cell diffusion of the factor(s) eliciting the stimulus;
      and/or since hypertonic osmotic pressure causes striking differences between leaf
      cells and protoplasts in total RNA and protein synthesis, these differences might
      include the suppression of synthesis of the elicitor of hypersensitivity. 

PMID- 24318253
TI  - Determination of adenylate cyclase activity in a variety of organisms: Evidence
      against the occurrence of the enzyme in higher plants.
AB  - Adenylate cyclase activity was examined in a variety of organisms using a highly
      sensitive assay. Activity was found in a blue-green alga, four green algae, two
      cellular slime molds, a fungus and moss protonemata. Fern prothalli and fronds
      gave variable results. No activity was detected in any of the higher plant
      tissues tested. The results throw further doubt on the existence of adenosine
      3':5'-cyclic monophosphate in higher plants. 

PMID- 24318254
TI  - Heterogeneity of sulphur content in the storage proteins of pea cotyledons.
AB  - By means of crossed immunoelectrophoresis of the cotyledonary storage proteins of
      Pisum sativum L. it was shown that reduced accumulation of the legumin fraction,
      resulting from severe sulphur deficiency during growth, is accompanied by
      relative suppression of a quantitatively minor storage protein (Peak 3) shown
      previously by subunit analysis to be related to the vicilin series of
      holoproteins. The pattern of isotopic labelling of the storage proteins after
      injection of [(35)S]methionine into the pedicel during seed development under
      normal nutritional conditions indicated that Peak-3 protein, like legumin, has a
      relatively high content of sulphur amino-acids. Like certain of the vicilin
      molecules carrying the determinants responsible for Peak-4, Peak-3 protein binds
      selectively to concanavalin A. 

PMID- 24318255
TI  - Purification and restriction endonuclease mapping of soybean 18 S and 25 S
      ribosomal RNA genes.
AB  - The restriction endonuclease map of the 25 S and 18 S ribosomal RNA genes of a
      higher plant is presented. Soybean (Glycine max) rDNA was enriched by preparative
      buoyant density centrifugation in CsCl-actinomycin D gradients. The buoyant
      density of the rDNA was determined to be 1.6988 g cm(-3) by analytical
      centrifugation in CsCl. Saturation hybridization showed that 0.1% of the total
      DNA contains 25 S and 18 S rRNA coding sequences. This is equivalent to 800 rRNA
      genes per haploid genome (DNA content: 1.29 pg) or 3200 for the tetraploid
      genome. Restriction endonuclease mapping was performed with Bam H I, Hind III,
      Eco R I, and BstI. The repeating unit of the soybean ribosomal DNA has a
      molecular weight of 5.9.10(6) or approximately 9,000 kb. The 25 S and 18 S rRNA
      coding sequences were localized within the restriction map of the repeating unit
      by specific hybridization with either [(125)I]25 S or [(125)I]18 S rRNA. It was
      demonstrated that there is no heterogeneity even in the spacer region of the
      soybean rDNA. 

PMID- 24318256
TI  - The indirect role of 2,4-D in the maintenance of apical dominance in decapitated
      sunflower seedlings (Helianthus annuus L.).
AB  - When sufficient 2,4-D to maintain apical dominance for at least 21d was applied
      to the cut stem interface of sunflower seedlings which had been decapitated in
      the epicotyl, it could not be detected in the vicinity of the inhibited axillary
      buds 7d after application. Rather the 2,4-D concentrated at the stump apex where
      it was associated with formation of meristematic tissue. The results indicate an
      indirect role for 2,4-D in the maintenance of apical dominance in this system,
      possibly involving the induced meristematic activity. 

PMID- 24318257
TI  - Control of electron flow in intact chloroplasts by the intrathylakoid pH, not by
      the phosphorylation potential.
AB  - In the presence of nitrite or oxaloacetate, intact chloroplasts evolved oxygen at
      a significant rate for the initial 1 to 2 min of illumination. Subsequently,
      oxygen evolution was suppressed progressively. The suppressed oxygen evolution
      was stimulated strikingly by NH4Cl. The results indicate that coupled electron
      flow in intact chloroplasts is controlled in the light, and the control is
      released by NH4Cl. However, at low concentrations, NH4Cl was not an effective
      uncoupler of photophosphorylation in intact chloroplasts. Intrachloroplast ATP
      levels and ATP/ADP ratios were not significantly influenced by NH4Cl. In
      contrast, the quenching of 9-aminoacridine fluorescence, which can be used to
      indicate the intrathylakoid pH in intact chloroplasts, was reduced drastically
      even by low concentrations of NH4Cl. This suggests that the chloroplast
      phosphorylation potential is not in equilibrium with the proton gradient. In
      coupled chloroplasts, the intrathylakoid pH was lower in the light with nitrite
      than with oxaloacetate as electron acceptor. Electron flow was also more
      effectively controlled in chloroplasts illuminated with nitrite than with
      oxaloacetate. It is concluded that the intrathylakoid pH, not the phosphorylation
      potential, is a factor in the control of the rate of electron flow in intact
      chloroplasts. 

PMID- 24318258
TI  - The rough endoplasmic reticulum is the site of reserve-protein synthesis in
      developing Phaseolus vulgaris cotyledons.
AB  - Cytyledons of the common bean, Phaseolus vulgaris L., were incubated with
      radioactive amino acids at different stages of seed development. The proteins
      were fractionated by ion-exchange chromatography, sucrose gradients, and sodium
      dodecylsulfate (SDS) polyacrylamide gel electrophoresis. From 16 to 28 d after
      flowering about 40% of the incorporated radioactivity was associated with the
      polypeptides of vicilin and 10% with those of phytohemagglutinin.Polysomes were
      isolated from developing cotyledons 20-25 d after flowering and free polysomes
      were separated from membrane-bound polysomes. Aurintricarboxylic acid, an
      inhibitor of initiation in cell-free translation systems, did not inhibit the
      incorporation of amino acids into in-vitro synthesized proteins, indicating that
      synthesis was limited to the completion of already initiated polypeptides.
      Autofluorography of SDS-polyacrylamide gels showed that the two classes of
      polysomes made two different sets of polypeptides and that there was little
      overlap between these two sets.Four polypeptides similar in size to the 4
      polypeptides of vicilin were made by membrane-bound polysomes and not by free
      polysomes. Antibodies specific for vicilin bound to those 4 polypeptides. Free
      polysomes made only polypeptides which did not bind to antibodies specific for
      vicilin. Antibodies against phytohemagglutinin did not bind to any of the invitro
      synthesized polypeptides.The membranes to which the polysomes were bound were
      characterized on sucrose gradients and by electron microscopy. Polysomes
      recovered from membranes which banded on top of 35 and 50% sucrose synthesized
      the vicilin polypeptides most rapidly. These membrane fractions were rich in
      vesicles of rough endoplasmic reticulum (ER). The ER marker-enzyme NADH
      cytochrome-c reductase banded with an average density of 1.18 g/cm(3) (40% w/w
      sucrose) on continuous gradients. These experiments demonstrate that the ER is
      the site of vicilin synthesis in developing bean cotyledons. Quantitative
      determinations of several ER parameters (RNA and lipid-phosphate content, NADH
      cytochrome-c-reductase activity) show that expansion of the cotyledons is
      accompanied by a 4-6-fold increase in ER. 

PMID- 24318259
TI  - Cytokinin inhibition of respiration by cells and mitochondria of soybean, Glycine
      max (L.) Merrill.
AB  - Cells of a soybean tissue strain, suspended in an aerated liquid medium, caused
      disappearance of p-coumaric acid from the medium and oxidation of guaiacol,
      benzidine, pyrogallol, L-dihydroxyphenylalanine and L-epinephrine. Both the
      disappearance and the oxidations were inhibited by 6-benzylaminopurine (BAP) at a
      concentration of 0.5 mM. BAP at other concentrations either promoted or inhibited
      oxidation of epinephrine in precisely the pattern reported earlier for the
      disappearance of coumarate; therefore, the disappearance of coumarate probably
      involves its oxidation. The effectiveness of other cytokinins in inhibiting the
      oxidation was studied.At 0.5 mM, and perhaps even at 0.5 MUM, some of the several
      cytokinins tested inhibited oxygen consumption by the soybean cells. This
      inhibition, which did not require any of the above metabolizable compounds, was
      especially marked in the presence of cyanide, azide or Antimycin A, and was
      detectable in 10 min or less. Either Antimycin A or salicylhydroxamic acid alone
      promoted O2 consumption but together they were quite inhibitory. The soybean
      cells apparently have an alternate respiratory pathway and cytokinins may
      influence its operation.Several cytokinins at 0.5 mM, and perhaps at 0.5 MUM,
      also inhibited oxygen consumption by mitochondrial preparations from the soybean
      cells, the inhibition being evident in about 20 s. The consumption required a
      substrate such as malate, succinate or NADH. Cytokinins and related compounds
      varied in effectiveness as follows: BAP and 6-isopentenyla-minopurine >= 9
      tetrahydropyranyl-BAP > kinetin, ribosyl-isopentenylaminopurine, 9-methyl-BAP and
      9-methoxymethyl-BAP > 6,6-dimethylaminopurine and zeatin (slight activity) > 6
      methylaminopurine, nicotinamide and adenine (ineffective). To a great extent this
      order parallels the order of effectiveness of the compounds in causing cell
      division. Mitochondria, therefore, may contain a site for an important cytokinin
      action. 

PMID- 24318260
TI  - Seed reserve-protein glycosylation in an in vitro preparation from developing
      cotyledons of Phaseolus vulgaris.
AB  - A particulate preparation from developing cotyledons of Phaseolus vulgaris L. was
      incubated with uridine-5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc; [6
      (3)H]glucosamine), and by polyacrylamide gel electrophoretic analysis it was
      shown that the labeled (N-acetyl)glucosamine (GlcNAc) was incorporated into the
      principal reserve protein of the cotyledons, vicilin, and also into
      phytohemagglutinin. Some of the labeled product also reacted with antiserum to
      vicilin from mature seeds. In contrast it was not possible to detect the
      incorporation of labeled mannose from guanosine-5'-diphospho-D-mannose (GDP
      mannose; [U-(14)C]mannose) into either of these proteins by gel-electrophoretic
      analysis of the mannose-labeled products, but we did observe a low incorporation
      of mannose into material which reacted with antiserum to vicillin. The
      predominant glycosylation reaction in vitro was therefore probably a transfer of
      GlcNAc alone, rather than in combination with mannose as preformed
      oligosaccharide. 

PMID- 24318263
TI  - C-S coupling using a mixed-ligand Pd catalyst: a highly effective strategy for
      synthesizing arylthio-substituted heterocycles.

PMID- 24318264
TI  - Stimuli-responsive supramolecular gelation in ferrocene-peptide conjugates.

PMID- 24318265
TI  - A simple probe for the colorimetric detection of carbon dioxide.

PMID- 24318266
TI  - Control of the orientation and photoinduced phase transitions of macrocyclic
      azobenzene.
AB  - Photoinduced phase transitions caused by photochromic reactions bring about a
      change in the state of matter at constant temperature. Herein, we report the
      photoinduced phase transitions of crystals of a photoresponsive macrocyclic
      compound bearing two azobenzene groups (1) at room temperature on irradiation
      with UV (365 nm) and visible (436 nm) light. The trans/trans isomer undergoes
      photoinduced phase transitions (crystal-isotropic phase-crystal) on UV light
      irradiation. The photochemically generated crystal exhibited reversible phase
      transitions between the crystal and the mesophase on UV and visible light
      irradiation. The molecular order of the randomly oriented crystals could be
      increased by irradiating with linearly polarized visible light, and the value of
      the order parameter was determined to be -0.84. Heating enhances the thermal cis
      to-trans isomerization and subsequent cooling returned crystals of the
      trans/trans isomer.

PMID- 24318267
TI  - On the mechanism of hydrogen activation by frustrated Lewis pairs.
AB  - We report herein a comprehensive theoretical study of the thermodynamics and
      kinetics of molecular hydrogen activation by frustrated Lewis pairs (FLPs). A
      series of intermolecularly combined boranes (Lewis acids) and phosphines (Lewis
      bases), with experimentally established different reactivities towards H2, have
      been subjected to DFT and (SCS-)MP2 calculations, and analyzed in terms of their
      structural properties, the energetics of association of the FLPs, and the
      kinetics of their interactions with H2 and hydrogenation to the ion-pair
      products. The analysis included the following steps: 1) assessment of the
      ability/inability of the Lewis species to preorganize into FLPs with an optimum
      arrangement of the acid and base sites for preconditioning the reaction with H2 ,
      2) comprehension of the different thermodynamics of hydrogenation of the selected
      FLPs by comparing the Gibbs energies of the overall reactions, and 3) estimation
      of the mechanism of the activation of H2 by identifying the reaction steps and
      the associated kinetic barriers. The results of our studies correlate well with
      experimental findings and have clarified the reasons for the observed different
      reactivities of the investigated systems, ranging from reversible or
      nonreversible activation to no reaction with H2. The derived predictions could
      assist the future design of Lewis acid-base systems with desired properties and
      applicability as metal-free hydrogenation catalysts.

PMID- 24318268
TI  - Comparison of gas sorption properties of neutral and anionic metal-organic
      frameworks prepared from the same building blocks but in different solvent
      systems.
AB  - Two different 3D porous metal-organic frameworks, [Zn4O(NTN)2].10DMA.7H2O (SNU
      150) and [Zn5(NTN)4(DEF)2][NH2(C2H5)2]2.8DEF.6H2O (SNU-151), are synthesized from
      the same metal and organic building blocks but in different solvent systems,
      specifically, in the absence and the presence of a small amount of acid. SNU-150
      is a doubly interpenetrated neutral framework, whereas SNU-151 is a non
      interpenetrated anionic framework containing diethylammonium cations in the
      pores. Comparisons of the N2, H2, CO2, and CH4 gas adsorption capacities as well
      as the CO2 adsorption selectivity over N2 and CH4 in desolvated SNU-150' (BET:
      1852 m(2) g(-1)) and SNU-151' (BET: 1563 m(2) g(-1)) samples demonstrate that the
      charged framework is superior to the neutral framework for gas storage and gas
      separation, despite its smaller surface area and different framework structure.

PMID- 24318269
TI  - Energy-funneling-based broadband visible-light-absorbing bodipy-C60 triads and
      tetrads as dual functional heavy-atom-free organic triplet photosensitizers for
      photocatalytic organic reactions.
AB  - C60-bodipy triads and tetrads based on the energy-funneling effect that show
      broadband absorption in the visible region have been prepared as novel triplet
      photosensitizers. The new photosensitizers contain two or three different light
      harvesting antennae associated with different absorption wavelengths, resulting
      in a broad absorption band (450-650 nm). The panchromatic excitation energy
      harvested by the bodipy moieties is funneled into a spin converter (C60), thus
      ensuring intersystem crossing and population of the triplet state. Nanosecond
      time-resolved transient absorption and spin density analysis indicated that the
      T1 state is localized on either C60 or the antennae, depending on the T1 energy
      levels of the two entities. The antenna-localized T1 state shows a longer
      lifetime (tau(T)=132.9 MUs) than the C60-localized T1 state (ca. 27.4 MUs). We
      found that the C60 triads and tetrads can be used as dual functional
      photocatalysts, that is, singlet oxygen ((1)O2) and superoxide radical anion
      (O2(.-)) photosensitizers. In the photooxidation of naphthol to juglone, the
      (1)O2 photosensitizing ability of the C60 triad is a factor of 8.9 greater than
      the conventional triplet photosensitizers tetraphenylporphyrin and methylene
      blue. The C60 dyads and triads were also used as photocatalysts for O2(.-)
      mediated aerobic oxidation of aromatic boronic acids to produce phenols. The
      reaction times were greatly reduced compared with when [Ru(bpy)3Cl2] was used as
      photocatalyst. Our study of triplet photosensitizers has shown that broadband
      absorption in the visible spectral region and long-lived triplet excited states
      can be useful for the design of new heavy-atom-free organic triplet
      photosensitizers and for the application of these triplet photosensitizers in
      photo-organocatalysis.

PMID- 24318270
TI  - Cation-mediated conversion of the state of charge in uranium arene inverted
      sandwich complexes.
AB  - Two new arene inverted-sandwich complexes of uranium supported by siloxide
      ancillary ligands [K{U(OSi(OtBu)3)3}2(MU-eta(6):eta(6)-C7H8)] (3) and
      [K2{U(OSi(OtBu)3)3}2(MU-eta(6):eta(6)-C7H8)] (4) were synthesized by the
      reduction of the parent arene-bridged complex [{U(OSi(OtBu)3)3}2(MU-eta(6):eta(6)
      C7H8)] (2) with stoichiometric amounts of KC8 yielding a rare family of inverted
      sandwich complexes in three states of charge. The structural data and
      computational studies of the electronic structure are in agreement with the
      presence of high-valent uranium centers bridged by a reduced tetra-anionic
      toluene with the best formulation being U(V)-(arene(4-))-U(V), KU(IV)-(arene(4-))
      U(V), and K2U(IV)-(arene(4-))-U(IV) for complexes 2, 3, and 4 respectively. The
      potassium cations in complexes 3 and 4 are coordinated to the siloxide ligands
      both in the solid state and in solution. The addition of KOTf (OTf=triflate) to
      the neutral compound 2 promotes its disproportionation to yield complexes 3 and 4
      (depending on the stoichiometry) and the U(IV) mononuclear complex
      [U(OSi(OtBu)3)3(OTf)(thf)2] (5). This unprecedented reactivity demonstrates the
      key role of potassium for the stability of these complexes.

PMID- 24318271
TI  - Temporary intramolecular generation of pyridine carbenes in metal-free three
      component C-H bond functionalisation/aryl-transfer reactions.
AB  - Nucleophilic addition of pyridines to benzyne generates zwitterionic adducts that
      evolve by a rapid intramolecular proton shift to produce the corresponding
      pyridine carbenes, N-phenyl pyrid-2-ylidenes. In the presence of electrophilic
      ketones (isatin derivatives), the pyridylidenes can further react by an original
      bis-arylation reaction of the carbonyl compounds involving a formal pyridine C-H
      bond functionalisation. The overall transformation is an unprecedented three
      component reaction featuring a carbene intermediate. The mechanism of this
      transformation was examined in detail by using both experimental and theoretical
      approaches. It was found that the generation of N-phenyl pyrid-2-ylidene from
      pyridine and benzyne is energetically favoured, and that the corresponding
      carbene dimer can also form easily. Under the three-component reaction
      conditions, the pyridylidene preferentially adds to the ketone group of the
      isatin derivative to produce a zwitterionic adduct amenable to an intramolecular
      aryl transfer reaction by a concerted nucleophilic aromatic substitution. This
      peculiar reactivity for a carbene was compared to possibly competitive known
      reactions of stable carbenes with carbonyl compounds, and the reaction was found
      to be under thermodynamic control. The reported method of generation of N-phenyl
      pyrid-2-ylidenes and their reactivity with carbonyl compounds unlock new
      perspectives in organic synthesis.

PMID- 24318272
TI  - Loss of E-cadherin activates EGFR-MEK/ERK signaling, which promotes invasion via
      the ZEB1/MMP2 axis in non-small cell lung cancer.
AB  - Loss of E-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), can
      significantly affect metastatic dissemination. However, the molecular mechanism
      of EMT-associated metastatic dissemination by loss of E-cadherin still remains
      unclear in non-small cell lung cancers (NSCLCs). In the present study, we show
      that the knockdown of E-cadherin was sufficient to convert A549 NSCLC cells into
      mesenchymal type with the concurrent up-regulation of typical EMT inducers such
      as ZEB1 and TWIST1. Interestingly, the EMT-induced cells by E-cadherin depletion
      facilitate invasion in a matrix metalloproteinase-2 (MMP2)-dependent manner with
      aberrant activation of EGFR signaling. We demonstrated that the elevated
      invasiveness was a result of the activated EGFR-MEK/ERK signaling, which in turn
      leads to ZEB1 dependent MMP2 induction. These results suggest that the EGFR
      MEK/ERK/ZEB1/MMP2 axis is responsible for promoted invasion in EMT-induced
      NSCLCs. Consistently, ERK activation and loss of E-cadherin were both observed in
      the disseminating cancer cells at the invasive tumor fronts in NSCLS cancer
      tissues. Thereby, these data suggest that the EGFR-MEK/ERK signaling would be a
      promising molecular target to control aberrant MMP2 expression and consequent
      invasion in the EMT-induced NSCSLs. 

PMID- 24318273
TI  - Causal inference with missing exposure information: Methods and applications to
      an obstetric study.
AB  - Causal inference in observational studies is frequently challenged by the
      occurrence of missing data, in addition to confounding. Motivated by the
      Consortium on Safe Labor, a large observational study of obstetric labor practice
      and birth outcomes, this article focuses on the problem of missing exposure
      information in a causal analysis of observational data. This problem can be
      approached from different angles (i.e. missing covariates and causal inference),
      and useful methods can be obtained by drawing upon the available techniques and
      insights in both areas. In this article, we describe and compare a collection of
      methods based on different modeling assumptions, under standard assumptions for
      missing data (i.e. missing-at-random and positivity) and for causal inference
      with complete data (i.e. no unmeasured confounding and another positivity
      assumption). These methods involve three models: one for treatment assignment,
      one for the dependence of outcome on treatment and covariates, and one for the
      missing data mechanism. In general, consistent estimation of causal quantities
      requires correct specification of at least two of the three models, although
      there may be some flexibility as to which two models need to be correct. Such
      flexibility is afforded by doubly robust estimators adapted from the missing
      covariates literature and the literature on causal inference with complete data,
      and by a newly developed triply robust estimator that is consistent if any two of
      the three models are correct. The methods are applied to the Consortium on Safe
      Labor data and compared in a simulation study mimicking the Consortium on Safe
      Labor.

PMID- 24318274
TI  - Ovarian hydatid disease.
AB  - Hydatid disease, also known as Echinococcosis is a zoonosis caused by the larval
      stage of Echinococcus. The human cystic variant primarily affects liver and
      lungs. The pelvic location of the disease is a rare finding usually secondary to
      a ruptured liver cyst, although it may also appear as a primary lesion affecting
      the genital organs. Despite its rarity, in endemic areas, pelvic hydatid disease
      should be considered in the differential diagnosis of complex adnexal cystic
      mass, to make an appropriate treatment strategy. The suspected diagnosis is based
      on imaging studies and serodiagnostic techniques, in which a new field of
      research attempts to find a standardized test with sufficient sensitivity and
      specificity. We report a case of primary pelvic hydatid disease in postmenopausal
      women operated for suspected ovarian cancer.

PMID- 24318275
TI  - Media effect--Letter to the editor about the manuscript titled: increasing fear
      of adverse effects drops intention to vaccinate after the introduction of
      prophylactic HPV vaccine.

PMID- 24318276
TI  - Effects of probiotics for the treatment of bacterial vaginosis in adult women: a
      meta-analysis of randomized clinical trials.
AB  - PURPOSE: The aim of this study was to evaluate the evidence for probiotic use in
      the treatment of bacterial vaginosis (BV) in adult women. METHODS: The Cochrane
      Library, PubMed, CINAHL and EMBASE databases were searched to identify the
      relevant randomized controlled trials that investigated the effects of probiotics
      for the treatment of BV. Two independent authors used an Excel file to extract
      data and assessed trial quality. The primary outcome measure was the cure rate of
      BV. The meta-analysis was performed with the fixed-effects model or random
      effects model according to heterogeneity. RESULTS: A total of 1,304 patients from
      12 trials were subjected to meta-analysis. The pooled result showed that
      probiotics supplementation can significantly improve the cure rate in adult BV
      patients [risk ratio (RR) 1.53; 95 % confidence interval (CI) 1.19-1.97].
      Findings were slightly different when analyses were restricted to nine high
      quality studies (RR 1.60; 95 % CI 1.16-2.22). In a subgroup meta-analysis, a
      statistically significant beneficial effect of probiotics was observed in Europe
      populations and short-term follow-up days. CONCLUSION: Compared with the control
      arm, the limited evidence suggests that probiotics show a beneficial effect in
      patients who are suffering from BV. However, the results should be interpreted
      cautiously because of the heterogeneity among study designs. Further large-scale,
      well-designed RCTs on this topic are urgently needed.

PMID- 24318277
TI  - Complete hydatidiform mole and a coexistent fetus following ovulation induction
      in a patient with Sheehan's syndrome: a first case report and review of
      literature.
AB  - Pregnancy in Sheehan's syndrome (SS) is extremely rare. We present the first
      reported case of twin pregnancy with complete hydatiform mole (CHM) and a
      coexistent fetus (CHCF) in a patient with SS. A 29-year-old Chinese patient with
      SS became pregnant following one cycle of ovulation induction with human
      menopausal gonadotropin after secondary infertility. A normal live fetus and a
      low echogenic mass suspected hydatidiform mole (HM) were detected by ultrasound
      examinations at gestational week 8. The couple highly desired to continue the
      pregnancy because it is very hard to get pregnant for the patients with SS.
      However, the pregnancy was terminated for the size of the HM component increased
      rapidly at gestational week 15. Histological examinations confirmed CHCF. Genetic
      studies showed that the CHM genome was derived from paternal diploidy, and the
      normal fetus was from biparental genomes. Furthermore, a literature review on
      these topics is included. This case highlighted that even in a patient with SS,
      twin pregnancy with CHCF can still occur after ovulation induction.

PMID- 24318278
TI  - Reallocating time to sleep, sedentary behaviors, or active behaviors:
      associations with cardiovascular disease risk biomarkers, NHANES 2005-2006.
AB  - Sleep and sedentary and active behaviors are linked to cardiovascular disease
      risk biomarkers, and across a 24-hour day, increasing time in 1 behavior requires
      decreasing time in another. We explored associations of reallocating time to
      sleep, sedentary behavior, or active behaviors with biomarkers. Data (n = 2,185
      full sample; n = 923 fasting subanalyses) from the cross-sectional 2005-2006 US
      National Health and Nutrition Examination Survey were analyzed. The amounts of
      time spent in sedentary behavior, light-intensity activity, and moderate-to
      vigorous physical activity (MVPA) were derived from ActiGraph accelerometry
      (ActiGraph LLC, Pensacola, Florida), and respondents reported their sleep
      duration. Isotemporal substitution modeling indicated that, independent of
      potential confounders and time spent in other activities, beneficial associations
      (P < 0.05) with cardiovascular disease risk biomarkers were associated with the
      reallocation of 30 minutes/day of sedentary time with equal time of either sleep
      (2.2% lower insulin and 2.0% lower homeostasis model assessment of beta-cell
      function), light-intensity activity (1.9% lower triglycerides, 2.4% lower
      insulin, and 2.2% lower homeostasis model assessment of beta-cell function), or
      MVPA (2.4% smaller waist circumference, 4.4% higher high-density lipoprotein
      cholesterol, 8.5% lower triglycerides, 1.7% lower glucose, 10.7% lower insulin,
      and 9.7% higher homeostasis model assessment of insulin sensitivity. These
      findings provide evidence that MVPA may be the most potent health-enhancing, time
      dependent behavior, with additional benefit conferred from light-intensity
      activities and sleep duration when reallocated from sedentary time. 

PMID- 24318279
TI  - Palermo et al. respond to "Disclosure of gender-based violence".

PMID- 24318281
TI  - Diverse bacteria isolated from microtherm oil-production water.
AB  - In total, 435 pure bacterial strains were isolated from microtherm oil-production
      water from the Karamay Oilfield, Xinjiang, China, by using four media: oil
      production water medium (Cai medium), oil-production water supplemented with
      mineral salt medium (CW medium), oil-production water supplemented with yeast
      extract medium (CY medium), and blood agar medium (X medium). The bacterial
      isolates were affiliated with 61 phylogenetic groups that belong to 32 genera in
      the phyla Actinobacteria, Firmicutes, and Proteobacteria. Except for the
      Rhizobium, Dietzia, and Pseudomonas strains that were isolated using all the four
      media, using different media led to the isolation of bacteria with different
      functions. Similarly, nonheme diiron alkane monooxygenase genes (alkB/alkM) also
      clustered according to the isolation medium. Among the bacterial strains, more
      than 24 % of the isolates could use n-hexadecane as the sole carbon source for
      growth. For the first time, the alkane-degrading ability and alkB/alkM were
      detected in Rhizobium, Rhodobacter, Trichococcus, Micrococcus, Enterococcus, and
      Bavariicoccus strains, and the alkM gene was detected in Firmicutes strains.

PMID- 24318282
TI  - A stable in vitro method for assessing the toxicity of potassium cyanide and its
      antidote.
AB  - BACKGROUND: Hydrogen cyanide possesses a high acid-dissociation constant of 9.14,
      favoring its vaporization and depletion from the culture media at physiological
      pH, which may cause the cyanide toxicity unstable in vitro. OBJECTIVE: We
      investigated whether adjustment of culture medium pH stabilizes cyanide
      concentration and decreases the effective concentration of potassium cyanide
      (KCN). METHODS: Murine fibroblast cells were exposed to different concentrations
      of KCN in media maintained at pH 7.4 or 9.2, in the presence or absence of
      hydroxocobalamin. After incubation for 1 h, we evaluated medium pH, cyanide
      concentration, cytochrome activity, and cell viability. RESULTS: Cyanide
      concentration decreased to 18.8% in pH 7.4 medium compared to 83.2% in pH 9.2
      medium. A significant decrease in cytochrome activity was observed at 40 mM and
      1.25 mM KCN in pH 7.4 and pH 9.2 media, respectively. In pH 9.2 medium, dose
      dependent cytotoxicity of KCN and antidotal effects of hydroxocobalamin were
      observed. CONCLUSION: Adjustment of culture medium pH to 9.2 could stabilize
      cyanide concentration and decrease the effective concentration of KCN, allowing
      stable evaluation of KCN toxicity and antidotal efficacy.

PMID- 24318280
TI  - Invited commentary: disclosure of gender-based violence in developing countries.
AB  - The evolving concept of gender-based violence (GBV) is a multifaceted issue of
      public health significance. Until recently, most studies examining GBV have been
      conducted in North America. In this issue of the Journal, Palermo et al. (Am J
      Epidemiol. 2014;179(5):602-612) report their secondary analyses involving
      approximately 300,000 women from 24 developing countries who participated in
      Demographic and Health Surveys between 2004 and 2011. The focus of their article
      is on the prevalence and determinants of disclosure of GBV to formal authorities,
      including health care or legal professionals, police, and nongovernmental
      organizations. Their results indicate a wide gap between prevalence of GBV (40%)
      and GBV disclosure (7%), implying an underestimation of GBV that ranges from 11-
      to 128-fold, depending on the region and type of reporting. The extent of
      underreporting of GBV also varied according to personal characteristics such as
      age, marital status and urban or rural residence. GBV has been linked to a myriad
      of health problems, and it has been shown that health care utilization is
      considerably higher among women who have experienced GBV. Primary and secondary
      prevention efforts should continue to target GBV, and creative ways of addressing
      GBV nondisclosure should take into account regional variations and personal
      characteristics of affected women. 

PMID- 24318283
TI  - Relationship between event-related desynchronization and cortical excitability in
      healthy subjects and stroke patients.
AB  - OBJECTIVE: Relation between cortical excitability and magnitudes of event-related
      dysynchronizaton (ERD) has not been clarified. This study was investigated that
      relationshp between cortical excitability and ERD magnitudes in healthy subjects
      and stroke patients. METHODS: Ten healthy subjects and four patients with stroke
      participated in this study. EEGs were recorded over the sensorimotor cortex (left
      hemisphere in healthy subjects; damaged hemisphere in stroke subjects) to
      calculate ERD during motor imagery,. Motor-evoked potential (MEP) induced by
      single-pulse transcranial magnetic stimulation over the primary motor cortex was
      recorded from the first dorsal interosseus (FDI) muscle at ERD magnitudes of 10%
      and 30%. RESULTS: MEP significantly increased at 10% and 30% ERD (p<0.01) than
      that during rest in healthy subjects. The 30% ERD condition showed significantly
      higher MEP than that at 10% ERD (p<0.05). In stroke patients, MEP increased with
      ERD induced by motor imagery, but the change of MEP to ERD amplitude was
      critically different among the subject. CONCLUSION: ERD magnitude corresponds to
      corticospinal excitability increases in healthy subjects and patients with
      hemiplegic stroke. BCI based on motor imagery-induced ERD may be a potential
      rehabilitation strategy for patients with hemiplegic stroke.

PMID- 24318284
TI  - Quercetin stimulates melanogenesis in hair follicle melanocyte of the mouse.
AB  - Quercetin (3, 3', 4', 5, 7-pentahydroxylflavone) is one of the representative
      flavonoids and is present in many vegetables and fruits. We studied the effects
      of quercetin on melanin production in hair follicle tissues from the buccal
      region of C3H/HeN Jel mice. These follicle tissues synthesized larger amounts of
      melanin than control tissue, with the amount dependent on the concentration of
      added quercetin. Additionally, the expression of tyrosinase protein was
      significantly enhanced in proportion to increases in the concentration of
      quercetin added. Nevertheless tyrosinase mRNA expression was not changed. In
      addition, tyrosinase-related protein-2 (TRP-2), which is a melanogenic enzyme,
      was increased depending on the concentration of added quercetin but its mRNA
      expression was not altered. These results show that quercetin stimulates the
      synthesis of tyrosinase protein as well as TRP-2 protein, thereby enhancing
      melanin producibility in hair follicle tissues from the buccal region of C3H/HeN
      Jel mice. 

PMID- 24318285
TI  - Estimation of environmental control measures for tuberculosis transmission in
      care facilities for the elderly.
AB  - OBJECTIVES: Exogenous reinfections in tuberculosis (TB) have been reported among
      elderly patients in long-term care facilities. This study estimated the impact of
      upper room ultraviolet germicidal irradiation (UVGI) and negative air ionization
      on the reduction in TB infection assuming that current TB control failed.
      METHODS: Estimated probability distributions RA, RM, RUV+M, and RIO+M, denoting
      the reproduction numbers of cases with no intervention, wearing surgical mask of
      infector, upper room UVGI, and negative ionization with wearing mask,
      respectively were determined. RESULTS: It was assumed that 1 TB patient and 29
      susceptibles stayed for 10 hours per day when ACH was 3; all subjects stayed for
      60 consecutive days. The median RA increased from 7.38 (15th day) to 11.72 (two
      month). The percent reductions of RM, RUV+M, and RIO+M ranged from 52.4% (15th
      day) to 41.6% (two month), from 76.6% to 68.3%, and from 74.9% to 63.0%,
      respectively. The percent reductions of slopes; the change of median RM, RUV+M,
      and RIO+M for a change in length of stay, were estimated to be 50.8%, 87.3% and
      73.7% when ACH was 1. CONCLUSIONS: In addition to case detection and source
      control measures, environmental control measures may be effective in preventing
      exogenous reinfection of TB in elderly care facilities.

PMID- 24318287
TI  - Localization of aPKC lambda/iota and its interacting protein, Lgl2, is
      significantly associated with lung adenocarcinoma progression.
AB  - Atypical protein kinase C lambda/iota (aPKC lambda/iota) is expressed in several
      human cancers; however, the correlation between aPKC lambda/iota localization and
      cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We
      found that patients with a high level of aPKC lambda/iota expression in LAC had
      significantly shorter overall survival than those with a low level of aPKC
      lambda/iota expression. In addition, localization of aPKC lambda/iota in the
      apical membrane or at the cell-cell contact was associated with both lymphatic
      invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was
      decreased in LACs with highly expressed aPKC lambda/iota at the invasion site of
      tumor cells. This result suggested that the expression levels of aPKC lambda/iota
      and E-cadherin reflect the progression of LAC. On double-immunohistochemical
      analysis, aPKC lambda/iota and Lgl2, a protein that interacts with aPKC
      lambda/iota, were co-localized within LACs. Furthermore, we found that Lgl2 bound
      the aPKC lambda/iota-Par6 complex in tumor tissue by immune-cosedimentation
      analysis. Apical membrane localization of Lgl2 was correlated with lymphatic
      invasion and lymph node metastasis. These results thus indicate that aPKC
      lambda/iota expression is altered upon the progression of LAC. This is also the
      first evidence to show aPKC lambda/iota overexpression in LAC and demonstrates
      that aPKC lambda/iota localization at the apical membrane or cell-cell contact is
      associated with lymphatic invasion and metastasis of the tumor. 

PMID- 24318286
TI  - Lobectomy of pulmonary metastasis of endometrial stromal sarcoma.
AB  - Pulmonary metastasis of low-grade endometrial stromal sarcoma is rare. A 61-year
      old woman visited our hospital due to an abnormal chest shadow. Computed
      tomograhy showed a mass that was composed of a cystic and solid lesion, in the
      right lower lobe. She had undergone a combination of a hysterectomy and
      adnexectomy for a low-grade endometrial stromal sarcoma 57 months previously, and
      undergone adjuvant radiation therapy at the local site. To obtain a definitive
      diagnosis of the lung tumor, we performed lobectomy of the right lower lobe and
      lymph node dissection. To avoid possible dissemination, the tumor was resected
      not using video-assisted thoracic surgery but using thoracotomy. The pathologic
      diagnosis was pulmonary metastasis of the low-grade endometrial stromal sarcoma.
      Now, medroxyprogesterone acetate is being administered, and no signs of
      recurrence have been detected in the 24 months since the lung resection. 

PMID- 24318288
TI  - Assessment of renal shape of horseshoe kidney with multidetector row CT in adult
      patients: relationship between urolithiasis and renal isthmus.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between
      urolithiasis and characteristics of renal shape in adult patients with horseshoe
      kidney (HSK) diagnosed on multidetector row computed tomography (MDCT). METHODS:
      We evaluated 36 patients with HSK and urolithiasis (Group A) and 70 patients with
      HSK without urolithiasis (Group B) whose disease was diagnosed on non-contrast
      MDCT. Two radiologists measured minimum width of the renal isthmus and maximum
      length of the renal pelvis and evaluated coexisting neoplastic diseases on axial
      computed tomographic (CT) images with 5-mm reconstruction, and we compared those
      measurements between the Groups A and B. RESULTS: The overall mean maximum length
      of the renal pelvis, 12.7+/-9.2 mm, did not differ significantly between the 2
      groups. Minimum isthmus width was larger in patients with HSK and urolithiasis
      (11.0+/-5.6 mm), than those without urolithiasis (9.5+/-5.1 mm). No patient in
      either groups had a urological renal tumor. CONCLUSIONS: Patients of HSK might
      have tendency of a high incidence of stone formation. Because urolithiasis is a
      risk factor for tumors of the renal pelvis, monitoring of patients with HSK
      requires careful attention to isthmus width on CT images.

PMID- 24318289
TI  - Reply to letter to editor "obturator hernia with kyphosis". Kim YW, Kim IY. DOI
      10.1007/s10029-013-1189-1.

PMID- 24318291
TI  - Recombinant human elastin-like magnetic microparticles for drug delivery and
      targeting.
AB  - Bioinspired recombinant polypeptides represent a highly promising tool in
      biomedical research, being protein intrinsic constituents of both cells and their
      natural matrices. In this regard, a very interesting model is represented by
      polypeptides inspired by elastin, which naturally confers rubber-like elasticity
      to tissues, and is able to undergo wide deformations without rupture. In this
      paper, a microparticle system based on a recombinant human elastin-like
      polypeptide (HELP) is reported for drug delivery applications. HELP
      microparticles are prepared through a water-in-oil emulsion of an aqueous
      solution of recombinant polypeptide in isoctane, followed by enzymatic cross
      linking. Superparamagnetic iron oxide nanoparticles are introduced in this system
      with the purpose of conferring magnetic properties to the microspheres, and thus
      controlling their targeting and tracking as drug vectors. The obtained
      microparticles are characterized in terms of morphology, structure, magnetic
      properties, drug release, and magnetic drivability, showing interesting and
      promising results for further biomedical applications. 

PMID- 24318292
TI  - Passage.

PMID- 24318293
TI  - Medical resistance, crisis ministry, and terminal illness.

PMID- 24318290
TI  - Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study.
AB  - OBJECTIVE: Whether febrile status epilepticus (FSE) produces hippocampal
      sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our
      objective is to determine whether FSE produces acute hippocampal injury that
      evolves to HS. METHODS: FEBSTAT and 2 affiliated studies prospectively recruited
      226 children aged 1 month to 6 years with FSE and controls with simple febrile
      seizures. All had acute magnetic resonance imaging (MRI), and follow-up MRI was
      obtained approximately 1 year later in the majority. Visual interpretation by 2
      neuroradiologists informed only of subject age was augmented by hippocampal
      volumetrics, analysis of the intrahippocampal distribution of T2 signal, and
      apparent diffusion coefficients. RESULTS: Hippocampal T2 hyperintensity, maximum
      in Sommer's sector, occurred acutely after FSE in 22 of 226 children in
      association with increased volume. Follow-up MRI obtained on 14 of the 22 with
      acute T2 hyperintensity showed HS in 10 and reduced hippocampal volume in 12. In
      contrast, follow-up of 116 children without acute hyperintensity showed abnormal
      T2 signal in only 1 (following another episode of FSE). Furthermore, compared to
      controls with simple febrile seizures, FSE subjects with normal acute MRI had
      abnormally low right to left hippocampal volume ratios, smaller hippocampi
      initially, and reduced hippocampal growth. INTERPRETATION: Hippocampal T2
      hyperintensity after FSE represents acute injury often evolving to a radiological
      appearance of HS after 1 year. Furthermore, impaired growth of normal-appearing
      hippocampi after FSE suggests subtle injury even in the absence of T2
      hyperintensity. Longer follow-up is needed to determine the relationship of these
      findings to TLE.

PMID- 24318295
TI  - Psychotherapy and the fat lady.

PMID- 24318294
TI  - Mystical and archetypal experiences of terminal patients in DPT-assisted
      psychotherapy.

PMID- 24318296
TI  - Family and synagogue: Partners in a search for the holy.

PMID- 24318297
TI  - Teaching meditation to medical students.

PMID- 24318298
TI  - Rabbinic theology and the unconscious.

PMID- 24318299
TI  - DNA synthesis in isolated mitochondria and mitochondrial extracts from wheat
      embryos.
AB  - DNA synthesis was studied using purified wheat embryo mitochondria as well as
      mitochondrial lysates deprived of endogenous DNA. The optimal conditions for DNA
      synthesis are very similar in both systems: ATP stimulates dramatically
      mitochondrial DNA synthesis and magnesium is a better co-factor than manganese,
      contrary to what has been reported in animal mitochondrial systems. Wheat
      mitochondrial DNA synthesis is resistant to aphidicolin and strongly inhibited by
      dideoxythymidine triphosphate and ethidium bromide. Thus, the DNA polymerase
      involved in this system seems to be the same as that previously purified and
      characterized from wheat embryo mitochondria (Christopheet al., Plant Science
      Letters 21: 181, 1981). Two different approaches: restriction endonuclease
      digestion followed by electrophoresis, and autoradiography and cesium chloride
      equilibrium centrifugation of mitochondrial DNA, where BrdUTP has been
      incorporated instead of TTP, show that long stretches of the mitochondrial genome
      have been synthesized. 

PMID- 24318300
TI  - Polymorphism of mitochondrial DNA 'S' regions among normal cytoplasms of maize.
AB  - Genomic variation in S1 and S2 homologous sequences, defined as the S regions,
      were examined in mitochondrial DNAs of 12 normal cytoplasm maize lines collected
      in the United States. Three genomic variants were detected among the 12
      cytoplasms, eight of which were identical to the Wf9 model structure.
      Hybridization data with S1 and S2 DNAs and with two cosmids spanning these
      regions were consistent with the concept that S1 and S2 sequences are found in
      each normal cytoplasm. Three variations of the S1 region were established; the
      Wf9 structure, a second group consisting of F6, A188, and W182BN, and a third,
      Black Mexican. Genome structure was conserved through the S2 region in all lines
      examined. None of the cytoplasms included complete copies of S1; the 1400 bp
      repeat characteristic of S1 and S2 was absent in the S1 region of all lines. A
      2.1 kb linear DNA was observed instead of a 2.3 kb DNA in F6, A188, and W182BN.
      Integrated copies of S1 and S2 sequences may be a constituitive characteristic of
      normal, male-fertile maize cytoplasms. 

PMID- 24318301
TI  - Developmental biochemistry of cottonseed embryogenesis and germination : XVI.
      Analysis of the principal cotton storage protein gene family with cloned cDNA
      probes.
AB  - DNAs complementary to the mRNAs coding for the major cotton 48 kD and 52 kD
      storage proteins have been cloned and used to characterize the principal cotton
      storage protein gene family. The principal storage proteins are found to emanate
      from three subsets of genes that share some homology, as shown by common
      antigenic determinants shared by the proteins themselves, but that are
      distinguishable by nucleic acid hybridization. A single sequence subfamily of
      2.26 kb mRNAs codes for the 69 kD preproteins (precursors to the mature 48 kD
      proteins) and two sequence subfamilies of 1.96 kb mRNAs each code for 60 kD
      preproproteins (precursors to the mature 52 kD proteins). Hybrid arrested
      translation shows that cloned members of these three subfamilies hybridize only
      with the mRNAs of a single subfamily at moderate criterion. These three
      subfamilies comprise all of the principal storage protein mRNAs detectable byin
      vitro translation. With hybridization at low criterion, some homology has been
      detected between the two 1.96 kb mRNA families, although no homology has yet been
      detected between the 2.26 kb mRNA family and either of the two 1.96 kb mRNA
      families. 

PMID- 24318302
TI  - Developmental biochemistry of cottonseed embryogenesis and germination : XVII.
      Developmental expression of genes for the principal storage proteins.
AB  - The developmental time period and the magnitude of expression of the genes for
      the principal cottonseed storage proteins have been measured by several means.
      RNA was extracted from cotton cotyledons at stages during embryogenesis and the
      relative amounts of the mRNAS for these proteins were determined by cell-free
      translation in the wheat germ system and by dot and northern hybridization of the
      RNA with cloned cDNA probes representing the three subfamilies of the major
      storage protein genes. The rates of reassociation in solution of some of the RNAs
      with one of the cDNA clones were also determined. Data from all four procedures
      show that the storage protein mRNAs are demonstrable in very small embryo
      cotyledons, rapidly reach a high abundance level that is maintained during most
      of embryo growth, and then fall precipitously in amount in the last days of
      embryogenesis. The expression of all three gene subfamilies appears
      coordinate.Further, cDNA reverse transcribed from the poly(A)(+) mRNA from a
      stage of maximum storage protein synthesis was hybridized to saturation with cDNA
      clones representing each of the subfamilies. These data indicate that the mRNAs
      for two of the families reach the same relative level in the total mRNA
      population which is about 15% of the total mRNA mass. The mRNA of the third
      subfamily comprises only 5% of the total mRNA mass at this stage. This apparent
      3?3?1 ratio of mRNAs does not change during the period of storage protein
      synthesis. Based on the amounts of the storage protein species in the mature
      seed, the mRNAs of each subfamily appear to be translated to the same extent
      during embryogenesis. 

PMID- 24318303
TI  - Fractionation and characterization of histones from barley (Hordeum vulgare)
      leaves : Existence of multiple H2A and H2B variants.
AB  - Histones were extracted from purified nuclei isolated from four cereals,viz.
      barley (Hordeum vulgare), wheat(Triticum aestivum), Aegilops squarrosa and corn
      (Zea mais), and from tobacco (Nicotiana tabacum). Analysis of the histones on SDS
      gels showed complex electrophoretic patterns with one species of both H3 and H4,
      one to three species of H1 and two to five species of H2. Judged from the
      electrophoretic patterns, the histones from barley, wheat and Aegilops are
      identical but different from those of corn with respect to H2. Like tobacco, corn
      showed two H2 components, whereas barley, wheat and Aegilops showed five H2
      components.SDS gel electrophoresis of histones extracted from buds and roots of
      germinating seeds at different steps of germination and from different parts of
      ten-day-old leaves revealed that the existence in barley of multiple histone 2
      variants is not restricted to any particular stage of differentiation of
      barley.Histones from barley leaves were resolved into four fractions by Biogel P
      100 gel filtration and histones 2 were further fractionated by their differential
      solubility in HCl-ethanol. Each of these five fractions (H1, H3, H4, H2A and H2B,
      respectively) were characterized by electrophoresis on SDS or Triton-acid-urea
      gels and by their amino acid compositions as compared with the homologous
      histones of calf thymus and chicken erythrocytes. This revealed the following: i)
      H3 and H4 are strictly analogous to their animal counterparts. However, H4 has an
      unexplained lower electrophoretic mobility in Triton-containing acid-urea gels.
      ii) H1 contains three components with lower electrophoretic mobilities than H1
      from erythrocytes, contains more alanine than lysine and has a lower ratio of
      basic to acidic residues. iii) Both H2A and H2B contain at least four variants
      each, with higher molecular weights than in animals and higher lysine to arginine
      ratios. H2A variants comigrate in acid-urea-Triton gels with chicken erythrocytes
      H2A, whereas H2B migrate much slower. It was concluded that the presence of
      multiple major variants of H2A and H2B is a frequent but not universal feature in
      cereals. The existence of these variants is not restricted to the embryonic stage
      as previously suggested for wheat (31). 

PMID- 24318306
TI  - The effect of partial fibulectomy on contact pressure of the knee: a cadaveric
      study.
AB  - PURPOSE: The fibula is a valuable source of bone graft and partial or total
      fibulectomy is done in some procedures, such as upper tibial osteotomy and
      treatment of tibial nonunion. Previous studies emphasized donor-site morbidity
      after fibulectomy. The aim of our study was to quantitatively survey joint
      reaction forces in the medial and lateral compartments of the ipsilateral knee,
      after partial fibulectomy. METHODS: Using left knees of six cadavers, after
      medial and lateral arthrotomy and total meniscectomy, Fuji pressure-sensitive
      film was inserted to both lateral and medial knee compartments. Weight bearing
      was simulated using a novel device that allowed a defined axial force to be
      applied to the left lower limbs of supine cadavers. The axial force of half the
      body weight of each specimen was applied to the plantar surface of the foot.
      After removing the films, fibulectomy was done 12 cm proximal to lateral
      malleolus and 2 cm of fibula harvested. The examination was repeated again in the
      same manner with new films. The resulting Fuji films were scanned using HP
      Scanjet (G3110) with resolution of 4,800 * 9,600 dpi. Films interpreted using
      software for Fuji pressure-sensitive film analysis. RESULTS: Joint reaction force
      was decreased in the medial compartment (P = 0.028) and increased in the lateral
      compartment (P = 0.027) after partial fibulectomy. Our study also showed that
      pressure changes over the medial and lateral compartments of the knee were not
      dependent on body weight (P = 0.787 for the medial compartment and P = 0.872 for
      the lateral compartment) and decreasing pressure in medial compartment was not
      depended on increasing pressure in lateral compartment (P = 0.208 and correlation
      coefficient were 0.6). CONCLUSIONS: The current study demonstrated partial
      fibulectomy at 12 cm above lateral malleolus results in decreasing pressure in
      knee medial compartment and increasing pressure in knee lateral compartment.
      Further studies are needed to evaluate the clinical importance of partial
      fibulectomy.

PMID- 24318305
TI  - Potentiation of paclitaxel activity by curcumin in human breast cancer cell by
      modulating apoptosis and inhibiting EGFR signaling.
AB  - It has been suggested that combined effect of natural products may improve the
      treatment effectiveness in combating proliferation of cancer cells. Here, we
      examined the combined anticancer activities of compounds of three natural origin
      including baicalein, curcumin, and resveratrol with chemotherapy drug paclitaxel
      respectively, which showed that combination of paclitaxel with curcumin exhibited
      synergistic growth inhibition and induced significant apoptosis in MCF-7 cell
      lines. Treatment of MCF-7 cell lines with paclitaxel and curcumin induced the
      apoptosis of regulatory protein Bcl-2 but decreased Bax expression. In addition,
      simultaneous treatment with paclitaxel and curcumin strongly inhibited paclitaxel
      induced activities of EGFR signaling. Furthermore, the combination of paclitaxel
      and curcumin exerted increased anti-tumor efficacy on mouse models. Overall, our
      data described the promising therapeutic potential and underlying mechanisms of
      combining paclitaxel with curcumin in treating breast cancer. 

PMID- 24318307
TI  - Role of muscle pedicle bone graft as an adjunct to open reduction and internal
      fixation in the management of neglected and ununited femoral neck fracture in
      young adults: a prospective study of 17 cases.
AB  - AIM: To evaluate the role of quadratus femoris muscle pedicle bone grafting along
      with open reduction and internal fixation in the treatment of neglected and
      ununited femoral neck fractures in young adults. MATERIALS AND METHODS: Young
      adults within the age group of 15-45 years with ununited, old neglected fractures
      of femoral neck were included in the study. All patients underwent quadratus
      femoris muscle pedicle bone grafting along with open reduction and internal
      fixation. The post-operative complications and functional recovery was assessed
      using Charnley's modification of Merle D'Aubigne and Postel hip scoring. RESULTS:
      A total of 17 patients were included in the study. The average time of union
      following the procedure was found to be approximately 8 months. There were two
      cases of delayed union and no cases of avascular necrosis. Ten patients (58.8%)
      had excellent or very good post-operative functional results and 6 patients
      (35.3%) had good or satisfactory results. CONCLUSION: Muscle pedicle bone
      grafting is a useful adjunct to open reduction and internal fixation for ununited
      femoral neck fractures. It achieves good final functional results comparable with
      other methods, but requires greater expertise.

PMID- 24318308
TI  - Acute pancreatitis after spine surgery: a case report and review of literature.
AB  - Although acute postoperative pancreatitis is a relatively frequent complication
      after open biliary tract surgery and gastric surgery, acute pancreatitis after
      spine surgery is a rare complication. We report the first case of acute
      pancreatitis after posterior lumbar interbody fusion (PLIF) for spondylolisthesis
      that resolved with conservative treatment. A 53-year-old female patient received
      a PLIF from L3 to L5. The patient presented with persistent mild abdominal pain,
      nausea and vomiting several hours after the surgery. An abdominal CT revealed
      swelling of the head of the pancreas and free fluid around the pancreas. A
      gastroenterologist diagnosed acute pancreatitis and prescribed nafamostat
      mesilate, antibiotics and intravenous fluid therapy. The patient recovered
      gradually, and clinical symptoms disappeared. At 6 months after the operation,
      she had experienced no recurrence of abdominal symptoms, and solid spinal fusion
      was achieved. In previous studies, acute pancreatitis was reported as a
      complication after spine surgery for various spine diseases such as scoliosis and
      lumbar disorders. The procedures performed included anterior/posterior scoliosis
      surgery and anterior/posterior lumbar fusion surgery. We must consider the
      possibility of acute pancreatitis when unusual abdominal symptoms with elevated
      serum amylase levels occur after spine surgery. Prompt diagnosis and supportive
      therapy are essential to minimize morbidity and mortality. 

PMID- 24318309
TI  - Assessment of the metabolic, protein, energy, and liver profiles of lambs
      finished in a feedlot and receiving diets containing groundnut cake.
AB  - Forty-five crossbred Dorper * Santa Ines lambs were selected to assess the effect
      of replacing soybean meal by groundnut cake metabolic profile and
      histopathological evaluation of the kidney and liver tissues. The animals were 5
      months old on average with a 24.5 +/- 5.3 kg initial body weight which were
      maintained fed in feedlot with groundnut cake (0, 25, 50, 75, and 100%) as the
      replacement for soybean meal. Confinement lasted 84 days, and on the last day,
      the animals were fasted and slaughtered. A completely randomized design with five
      treatments and nine repetitions was used. Blood samples were collected from the
      jugular vein of each animal to evaluate the metabolic, protein, energy, and liver
      profiles of lambs. No effect was observed on protein, energy, or enzymatic
      profiles, which remained within the normal range for sheep. A histopathological
      examination was performed, and no deleterious effects from groundnut cake were
      observed in the liver or kidney tissues. Groundnut cake as a replacement for
      soybean meal can be used as an alternative protein source up to 100% because it
      does not affect the metabolic, protein, and energy profiles or the liver and
      kidney functions of the growing sheep for slaughter.

PMID- 24318310
TI  - Mood variability and the psychosocial adjustment of adolescents.
AB  - This research uses a new time sampling method to compare adolescent and adult
      mood variability. Over 9000 self-reports from 182 people are used to evaluate the
      widespread theoretical assumption that adolescents experience greater mood
      variability as part of a syndrome of psychosocial disequilibrium. The findings
      confirm that adolescents experience wider and quicker mood swings, but do not
      show that this variability is related to stress, lack of personal control,
      psychological maladjustment, or social maladjustment within individual teenagers.
      Rather than representing turmoil, wide mood swings appear to be a natural part of
      an adolescent peer-oriented life style. However, there are indications that
      adolescent mood variability interferes with capacity for deep involvement,
      especially in school. 

PMID- 24318311
TI  - Perceived change of self among adolescents.
AB  - In order to examine the sense of continuity of adolescents, self-appraisals of
      retrospective and prospective change or sameness were elicited from Israeli boys
      and girls in grades 7, 9, and 11 (N=186). With reference to each of 60 self
      attributes, these adolescents indicated the amount of change they perceived in
      themselves, compared with what they were like five years ago. They then estimated
      how much they expected to change on each attribute five years from now. Most
      respondents perceived minimal change in themselves, both retrospectively and
      prospectively. Regression analyses indicated that the lower the amount of
      perceived change of self, the higher the level of self-perceived adjustment and
      self-ideal congruence. These findings are discussed in terms of their
      implications for future studies of the sense of continuity in adolescence and
      beyond. 

PMID- 24318312
TI  - Self-image of adolescents with cystic fibrosis.
AB  - Cystic fibrosis (CF) is a lethal genetic disease, yet improved care has extended
      the mean age of survival into the young adult years. Many of the surviving
      adolescents have respiratory and digestive problems which delay growth and sexual
      development. It has been suggested that the specter of fatal disease interferes
      with adjustment to adolescence. We administered the Offer Self-Image
      Questionnaire to three groups with mean height less than the fifth percentile: CF
      males aged 12-19 (n=16); CF females aged 12-19 (n=8); and otherwise healthy males
      with short stature and/or delayed puberty aged 13-19 (n=34). The values obtained
      were compared to published normative data for a large number of normal
      adolescents and a smaller number of adolescents actively undergoing treatment for
      emotional disorders. CF males showed an abnormal pattern of adjustment that could
      be considered comparable to disturbed males and to growth-delayed and sexually
      delayed males. The CF female group was concordant with the normal population,
      rather than with the emotionally disturbed population. Thus CF and pubertally
      delayed males have a self-perception of maladjustment to the psychologic problems
      of adolescence. This suggests that adjustment problems of the CF male may be
      related to growth retardation and pubertal delay, the social stigma of which may
      be more easily disguised in the female. This is important in health care, since
      recent evidence suggests that exemplary attention to medical compliance and
      nutrition may ameliorate some of the growth lag both in pubertal delay and CF. 

PMID- 24318313
TI  - Parental influences on the development of adolescent autonomy and identity.
AB  - Two studies were undertaken to examine parental influences on autonomy and
      identity development. In Study 1, 262 adolescents in seventh and eleventh grades
      were given Kurtines's autonomy measure, Simmons's identity measure, and Elder's
      questions regarding the adolescents' perceptions of their parents' autocratic,
      democratic, or permissive parenting styles. Study 2 was a replication with 168
      subjects. Across both studies it was found that sex-role socialization is more
      influential for automony development than is either level of parental power or
      age. Both age and father's use of democracy were the most influential variables
      on identity development. 

PMID- 24318314
TI  - The effects of college on students' partisanship: A research note.

PMID- 24318315
TI  - Interpersonal perceptions within families containing behavior problem
      adolescents.

PMID- 24318316
TI  - Chromo-fluorogenic detection of nitroaromatic explosives by using silica
      mesoporous supports gated with tetrathiafulvalene derivatives.
AB  - Three new hybrid gated mesoporous materials (SN3 -1, SNH2 -2, and SN3 -3) loaded
      with the dye [Ru(bipy)3 ](2+) (bipy=bipyridine) and capped with different
      tetrathiafulvalene (TTF) derivatives (having different sizes and shapes and
      incorporating different numbers of sulfur atoms) have been prepared. The
      materials SN3 -1 and SN3 -3 are functionalized on their external surfaces with
      the TTF derivatives 1 and 3, respectively, which were attached by employing the
      "click" chemistry reaction, whereas SNH2 -2 incorporates the TTF derivative 2,
      which was anchored to the solid through an amidation reaction. The final gated
      materials have been characterized by standard techniques. Suspensions of these
      solids in acetonitrile showed "zero release", most likely because of the
      formation of dense TTF networks around the pore outlets. The release of the
      entrapped [Ru(bipy)3 ](2+) dye from SN3 -1, SNH2 -2, and SN3 -3 was studied in
      the presence of selected explosives (Tetryl, TNT, TNB, DNT, RDX, PETN, PA, and
      TATP). SNH2 -2 showed a fairly selective response to Tetryl, whereas for SN3 -1
      and SN3 -3 dye release was found to occur with Tetryl, TNT, and TNB. The
      uncapping process in the three materials can be ascribed to the formation of
      charge-transfer complexes between the electron-donating TTF units and the
      electron-accepting nitroaromatic explosives. Finally, solids SNH2 -2 and SN3 -1
      have been tested for Tetryl detection in soil with good results, pointing toward
      a possible use of these or similar hybrid capped materials as probes for the
      selective chromo-fluorogenic detection of nitroaromatic explosives. 

PMID- 24318317
TI  - Hearing loss following ventriculoperitoneal shunt in communicating hydrocephalus
      patients: a pilot study.
AB  - OBJECTIVES/HYPOTHESIS: Hearing loss can be associated with a decrease in
      cerebrospinal fluid (CSF) pressure because changes in CSF pressure induce changes
      in perilymph pressure. Hearing loss after neurosurgical procedures have been
      reported, but clinical information on hearing loss after the placement of
      ventriculoperitoneal (VP) shunts, the most commonly used CSF shunt for
      hydrocephalus patients, is limited. This study is aimed to show the relationship
      between VP shunt and hearing loss. STUDY DESIGN: Prospective study. METHODS: Pure
      tone threshold and electrocochleography were preoperatively performed in nine
      patients (18 ears) undergoing elective VP shunt placement. Five-day and 1-month
      post-shunt placement hearing thresholds were compared with baseline data. A
      correlation analysis was conducted between the threshold and summating
      potential/action potential (SP/AP) ratio changes at 5 days and 1 month after
      shunt placement. Cochlear aqueduct dimensions measured by high-resolution CT were
      compared between ears with and without hearing loss. RESULTS: About 40% of
      subject ears showed hearing loss with a threshold elevation of at least 15 dB in
      one or more frequencies. After VP shunt placement, the mean threshold of all ears
      showed a significant increase in most frequencies and the pure tone average. The
      change in the SP/AP ratios was significantly correlated with the change in the
      pure tone average at both 5 days and 1 month after shunt placement. Cochlear
      aqueduct dimensions were not correlated with hearing loss occurrence.
      CONCLUSIONS: Hearing thresholds may increase following VP shunt placement,
      possibly due to secondary endolymphatic hydrops.

PMID- 24318318
TI  - Blood transfusion after primary total knee arthroplasty can be significantly
      minimised through a multimodal blood-loss prevention approach.
AB  - PURPOSE: Our aim was to clarify the effective decrease in blood transfusion after
      primary total knee arthroplasty (TKA) from a multimodal blood-loss prevention
      approach (MBLPA) and the related risk factors of blood transfusion. METHODS: We
      retrospectively compared the rate of postoperative blood transfusion in 418 cases
      of primary TKA during 2010 from a single institution with two different groups of
      patients, allocating cases to the group with MBLPA (group 1, study group, N = 71)
      and controls to the group without MBLPA (group 2, standard group, N = 347). MBLPA
      procedure included pre-operative haemoglobin (Hb) optimisation; femoral canal
      obturation; limited incision and release; peri- and intra-articular use of saline
      with adrenalin, morpheic chloride, tobramycin, betamethasone and ropivacaine;
      tourniquet release after skin closure; 24 hour drain under atmospheric pressure;
      and two doses of tranexamic acid (TXA) i.v.. In the control group, surgeons
      followed the standard procedure without blood-saving techniques. Case-control
      comparison and blood transfusion risk factors were analysed. RESULTS: Group 1 had
      a zero transfusion rate (0/71), whereas 27.4% of patients (95/347) in group 2
      received allogenic blood transfusion. Significant transfusion risk factors were
      pre-operative Hb <12 g/dl), American Society of Anesthesiologists (ASA) status
      III and nonobese body mass index (BMI); Age and gender were not significant risk
      factors. CONCLUSIONS: MBLPA in primary TKA was highly effective, with a zero
      transfusion rate. Risk factors for transfusion were determined, and eliminating
      them contributed to the avoidance of allogeneic blood transfusion in our study
      series.

PMID- 24318319
TI  - Prospective randomised controlled trial of an intramedullary nail versus a
      sliding hip screw for intertrochanteric fractures of the femur.
AB  - PURPOSE: The purpose of this prospective randomised trial was to assess whether
      an intramedullary nail is superior to a sliding hip screw in the treatment of
      multifragmentary intertrochanteric fractures METHODS: Eighty patients with a 31
      A2.2 or A2.3 Arbeitsgemeinschaft fur Osteosynthesefragen/Orthopaedic Trauma
      Association (AO/OTA) intertrochanteric fracture were randomly allocated to
      fixation with either the Gamma nail or the AMBI sliding hip screw device.
      RESULTS: All patients were followed up at one, three, six and 12 months
      postoperatively, except for nine who died. There was no statistical difference in
      Parker mobility score between groups. The Gamma nail group had significantly
      higher Barthel Index and EuroQol-5D (EQ-5D) scores than the AMBI group at 12
      months. At the same time, the EQ-5D score had returned to its pre-operative
      values in the Gamma nail group but not in the AMBI group. There were no
      differences in mortality, radiation time and hospital stay. Duration of the
      operation, incision length and hip pain occurrence were significantly less in the
      Gamma nail group. CONCLUSIONS: Few failures occur when unstable 31-A2.2 and A2.3
      AO/OTA fractures are fixed with a sliding hip screw. Nevertheless, an
      intramedullary nail seems superior in reconstituting patients to their pre
      operative state.

PMID- 24318320
TI  - Phallometric assessments of sexual interests: an update.
AB  - This paper reviews recent evidence on the value of phallometric (i.e., erectile)
      measures of sex offenders plus earlier crucial papers. Distinctions are made
      between types of measuring devices with the volumetric instrument appearing to be
      the most sensitive. Considering the meaning of responses it is concluded that
      arousal below 10 % of full erection is not reliably interpretable and that only
      deviant profiles (those displaying equal or greater arousal to deviant sex) can
      be confidently interpreted. The specificity and sensitivity of phallometry is
      satisfactory with child molesters but not with other types of sex offenders,
      although there remains a need to satisfactorily distinguish among subtypes of
      child molesters. There are enduring disagreements concerning the meaning of
      rapists' responses and no test has yet reliably identified deviance among
      exhibitionists. It is concluded that despite its long history, problems remain
      with phallometric assessments and clinicians should be cautious in interpreting
      the meaning of these responses. 

PMID- 24318321
TI  - Importance and utility of laparoscopic inguinal exploration in cases with chronic
      groin pain: Comment on: Laparoscopic diagnosis and management of a novel
      inguinopelvic hernia. Modeste K, Novitsky W. Hernia 2013 Jun 17: 419-422, doi:
      10.1007/s10029-012-0910-9.

PMID- 24318322
TI  - The major DNA polymerase in cultured plant cells: Partial purification and
      correlation with cell multiplication.
AB  - A DNA polymerase activity was isolated from cells of Oryza sativa L. grown in
      suspension culture. Molecular mass (~ 180,000), optimal requirements for pH
      (neutral), Mg(2+) (5-10 mM), Mn(2+) (1 mM), template preference (activated DNA),
      lack of activity with native or denatured DNA, and sensitivity to N
      ethylmaleimide and ionic strength are similar to those of the vertebrate alpha
      polymerase. Like DNA polymerase alpha, the DNA polymerase described in this work
      is the most abundant in proliferating cells of Oryza sativa L., Parthenocissus
      tricuspidata (Siebold et Zucc.) Planchon, Acer pseudoplatanus L., and Medicago
      sativa L. and responds to changes in the rate of cell multiplication. We
      therefore postulate that this alpha-like DNA polymerase is the replicating enzyme
      of plant cells. 

PMID- 24318323
TI  - Investigations on heat resistance of spinach leaves.
AB  - Exposure of spinach plants to high temperature (35 degrees  C) increased the heat
      resistance of the leaves by about 3 degrees  C. This hardening process occurred
      within 4 to 6 h, whereas dehardening at 20 degrees /15 degrees  C required 1 to 2
      days. At 5 degrees  C dehardening did not take place. Hardening and dehardening
      occurred in both the dark and the light. The hardiness was tested by exposure of
      the leaves to heat stress and subsequent measurements of chlorophyll fluorescence
      induction and light-induced absorbance changes at 535 nm on the leaves and of the
      photosynthetic electron transport in thylakoids isolated after heat treatment.
      Heat-induced damage to both heat-hardened and non-hardened leaves seemed to
      consist primarily in a breakdown of the membrane potential of the thylakoids
      accompanied by partial inactivation of electron transport through photosystem II.
      The increase in heat resistance was not due to temperature-induced changes in
      lipid content and fatty acid composition of the thylakoids, and no conspicuous
      changes in the polypeptide composition of the membranes were observed. Prolonged
      heat treatment at 35 degrees  C up to 3 days significantly decreased the total
      lipid content and the degree of unsaturation of the fatty acids of membrane
      lipids without further increase in the thermostability of the leaves. Intact
      chloroplasts isolated from heat-hardened leaves retained increased heat
      resistance. When the stroma of the chloroplasts was removed, the thermostability
      of the thylakoids was decreased and was comparable to the heat resistance of
      chloroplast membranes obtained from non-hardened control plants. Compartmentation
      studies demonstrated that the content of soluble sugars within the chloroplasts
      and the whole leaf tissue decreased as heat hardiness increased. This indicated
      that in spinach leaves, sugars play no protective role in heat hardiness. The
      results suggest that changes in the ultrastructure of thylakoids in connection
      with a stabilizing effect of soluble non-sugar stroma compounds are responsible
      for acclimatization of the photosynthetic apparatus to high temperature
      conditions. Changes in the chemical composition of the chloroplast membranes did
      not appear to play a role in the acclimatization. 

PMID- 24318324
TI  - The effect of vanadium on nitrate reductase of Chlorella vulgaris.
AB  - Added vanadate ions inhibit purified nitrate reductase from Chlorella vulgaris by
      reacting with the enzyme in a manner rather similar to that of HCN. Thus
      vanadate, like HCN, forms an inactive complex with the reduced enzyme, and this
      inactivated enzyme can be reactivated rapidly by adding ferricyanide. The
      inactive vanadate enzyme complex is less stable than the inactive HCN complex,
      and the two can be distinguished by the fact that EDTA causes a partial
      reactivation of the former, but not of the latter. Vanadate can also cause an
      increase in HCN formation by intact Chlorella vulgaris cells. When these cells
      were incubated with vanadate, their nitrate reductase was reversibly inactivated,
      and all of this inactive enzyme could be shown to be the HCN complex rather than
      the vanadate complex. When HCN and vanadate are both present, the HCN-inactivated
      enzyme, being more stable, will be formed in preference to the vanadate
      inactivated enzyme. 

PMID- 24318325
TI  - Evidence for two photoreceptors controlling growth in de-etiolated seedlings.
AB  - The effect of blue light on hypocotyl extension in de-etiolated seedlings of
      lettuce, cucumber and tomato was investigated under conditions which precluded
      the involvement of phytochrome. Small but highly inhibitory amounts of blue light
      were added to a high intensity background illumination from low pressure sodium
      lamps. A log-linear response for inhibition of hypocotyl extension against the
      blue light fluence rate was obtained for lettuce and cucumber, and inhibition in
      tomato was also related to the blue light fluence rate. The added blue light did
      not alter phytochrome photostationary state and its effect was independent of the
      total fluence rate. Growth inhibition by Pfr could be demonstrated in tomato and
      cucumber but not in lettuce. The results indicate that two photoreceptors may
      normally be involved in the control of seedling growth but their relative
      importance varies greatly between species. 

PMID- 24318326
TI  - The intensification of absorbance changes in leaves by light-dispersion :
      Differences between high-light and low-light leaves.
AB  - In dispersive samples, like leaves, the absorbance of pigments is intensified.
      The intensification is due to a longer optical path through the dispersive
      sample. However, in chloroplast suspensions the optical path is not much longer
      than in clear solutions. The factor of intensification beta (=the lengthening of
      the optical path) is calculated by comparing the absorbance of leaves and the
      absorbance of chloroplast suspensions with equal pigment-content. This method
      also includes the influence of possible sieve effects which could decrease
      absorbance. The measurements are carried out with high- and low-light leaves of
      different thickness and pigment content. The intensification of absorbance was 2
      2.5 fold. In highlight leaves it was somewhat less than in low-light leaves. The
      factor beta is better correlated to the pigment content than to the thickness of
      the leaves. The plot of absorbance versus the pigment content of the leaves shows
      that beta decreases with increasing pigment content. In contrast, chloroplast
      suspensions show a linear dependence as expected from Lambert-Beer's law. Thus,
      in leaves with very low pigment content the absorbance is intensified up to 6
      fold while the intensification decreases with increasing absorbance. These
      results are in good agreement with measurements of Tsel'niker (1975) and with the
      theoretical predictions of Butler's formula (1960). Absorbance changes due to
      photooxidation of P-700 and cytochrome f in intact leaves are measured, and beta
      is used to calculate the amount of the oxidized components. Without correction
      for beta the values would be much greater than the amount actually present. The
      corrected data show that between 70 and 90% of the present P-700 and cytochrome f
      can be photooxidized in the intact leaf. 

PMID- 24318327
TI  - Protein synthesis of binucleate and trinucleate pollen and its relationship to
      tube emergence and growth.
AB  - Under humid conditions, both bi- and trinucleate pollen species incorporate, on
      the average, very low amounts of leucine, e.g., 0.4 pmol min(-1)mg pollen(-1).
      During germination in vitro, however, the two types of pollens greatly differ in
      their capacity for protein synthesis.Binucleate pollen species such as Typha,
      which are characterized by slow respiration in humid air and prolonged lag
      periods during germination in vitro, contain large amounts of monoribosomes at
      dehiscence. Polyribosomes are formed soon after the pollen is wetted in the
      germination medium, and a considerable incorporation of leucine is initiated
      after 10-15 min. More rapidly respiring, binucleate pollen showing a short lag
      period, such as Tradescantia, may already contain many polysomes at dehiscence
      and incorporate leucine within 2 min of germination. However, rapidly respiring,
      trinucleate Compositae pollen contains very limited amounts of ribosomal material
      and never attains any substantial level of incorporation. Cycloheximide
      completely inhibits both protein synthesis and tube emergence and growth in the
      slowly respiring, binucleate pollen species. The more rapidly respiring types are
      less dependent on protein synthesis, while germination of the phylogenetically
      advanced, trinucleate Compositae pollen proceeds completely independently. It is
      concluded that the level of phylogenetic advancement of the male gametophyte is
      characterized by its overall state of metabolic development at dehiscence rather
      than by the number of its generative cells. 

PMID- 24318328
TI  - L-lactate dehydrogenase from leaves of Capsella bursa-pastoris (L.) Med. : I.
      Identification and partial characterization.
AB  - By ammonium sulfate fractionation and gel filtration an enzyme preparation which
      catalyzed NAD(+)-dependent L-lactate oxidation (10(-4) kat kg(-1) protein), as
      well as NADH-dependent pyruvate reduction (10(-3) kat kg(-1) protein), was
      obtained from leaves of Capsella bursa-pastoris. This lactate dehydrogenase
      activity was not due to an unspecific activity of either glycolate oxidase,
      glycolate dehydrogenase, hydroxypyruvate reductase, alcohol dehydrogenase, or a
      malate oxidizing enzyme. These enzymes could be separated from the protein
      displaying lactate dehydrogenase activity by gel filtration and electrophoresis
      and distinguished from it by their known properties. The enzyme under
      consideration does not oxidize D-lactate, and reduces pyruvate to L-lactate (the
      configuration of which was determined using highly specific animal L-lactate
      dehydrogenase). Based on these results the studied Capsella leaf enzyme is
      classified as L-lactate dehydrogenase (EC 1.1.1.27). It has a Km value of 0.25
      mmol l(-1) (pH 7.0, 0.3 mmol l(-1) NADH) for pyruvate and of 13 mmol l(-1) (pH
      7.8, 3 mmol l(-1) NAD(+)) for L-lactate. Lactate dehydrogenase activity was also
      detected in the leaves of several other plants. 

PMID- 24318329
TI  - Phytochrome and internode elongation in Chenopodium polyspermum L. the light
      fluence rate during the day and the end-of-day effect.
AB  - The elongation of the fourth internode of fully green Chenopodium polyspermum L.
      is strongly stimulated by far-red light (FR) given at the end of the day. The end
      of-day effect is more important when the plants had been cultivated for several
      days with a main light period of 140 Wm(-2) than with a main light period of 85
      Wm(-2). There exists a quantitative relationship between the FR end-of-day effect
      mediated by phytochrome and the value of the light fluence during the day. 

PMID- 24318330
TI  - The control of food mobilisation in seeds of Cucumis sativus L. : I. The
      influence of embryonic axis and testa on protein and lipid degradation.
AB  - The development of maximal rates of lipid and protein hydrolysis in cucumber
      cotyledons depends upon the removal of the testa and the presence of the
      embryonic axis. The testa appears to exert at least part of its inhibitory
      influence by suppressing the development of enzyme activity associated with
      lipolysis and proteolysis. There is, however, no evidence to suggest that the
      presence of the embryonic axis is a pre-requisite for the development of optimal
      enzyme activity. 

PMID- 24318331
TI  - The control of food mobilisation in seeds of Cucumis sativus L. : II. The role of
      the embryonic axis.
AB  - Removal of the embryonic axis from germinated cucumber seeds, either on the
      second of fourth day after imbibition, subsequently results in reduced rates of
      lipid and protein degradation and in the accumulation of free sugars and amino
      acids in the cotyledons. These isolated cotyledons show an inherent capacity for
      expansion growth which apparently results from an increased rate of water uptake.
      When water uptake is inhibited by incubating samples in polyethylene glycol the
      rate of lipid degradation is further reduced. This is accompanied by an
      additional increase in the reducing sugar and sucrose content of the cotyledons.
      Protein degradation in isolated cotyledons is inhibited to the same extent
      whether samples are incubated in water or polyethylene glycol. Furthermore, amino
      acid levels show appreciable and almost identical increases in both incubation
      media. Evidently an inverse correlation exists between rates of reserve
      mobilisation and levels of end products. It is suggested that the axis controls
      food mobilisation through a sink effect by reducing the levels of end products in
      the cotyledons. 

PMID- 24318332
TI  - Abscisic acid, abscisic acid-esters and phaseic acid in vegetative terminal buds
      of Acer pseudoplatanus during emergence from winter dormancy.
AB  - Levels of free-abscisic acid and "boundabscisic acid" (alkaline hydrolyzable
      abscisic acidesters) in replicated samples of terminal vegetative buds of
      sycamore trees were measured during natural emergence from winter dormancy by gas
      chromatographic methods together with isotope dilution estimation of recovery
      rates. Not until after the buds had been released from true dormancy in January
      by winter chilling did any clear change occur in either abscisic acid (ABA)
      fraction, or in total ABA, on any basis of comparison. The percentage of total
      ABA present as the free acid declined at the end of true dormancy to
      approximately two-thirds of its value in the earlier winter months. It is
      concluded that glucosylation of ABA is unlikely to play a major part in the
      mechanism of release from dormancy in vegetative sycamore buds. At the end of
      true dormancy there was a large transient increase in what appeared to be phaseic
      acid, but this was not accompanied by any marked decrease in either free- or
      bound-ABA. 

PMID- 24318333
TI  - The development of nuclear vacuoles during meiosis in plants.
AB  - Vacuoles formed by the invagination of the inner membrane of the nuclear envelope
      have been observed during meiotic prophase in a wide range of plants. In the
      angiosperm Lycopersicon their formation was found to coincide with the completion
      of synaptonemal complex formation, and this timing is analogous to that observed
      during this stage in the silkworm Bombyx. The implications of this activity in
      relation to the process of chromosome movement are discussed. In the gymnosperm
      Pinus, the heterosporous fern Marsilea and homosporous ferns Pteridium and
      Dryopteris the formation of nuclear vacuoles begins much earlier, coinciding with
      the condensation of chromatin during leptotene. They enlarge and become more
      elaborate as meiosis proceeds, and may eventually become detached from the
      nuclear envelope. It is therefore thought unlikely that theyfulfil functions
      connected with chromosome movement in the manner proposed for the silkworm and
      the tomato. During diplotene/diakinesis they contain electron-opaque granules and
      fibrils, and the possible origin and significance of this material is discussed. 

PMID- 24318334
TI  - The effect of temperature on the velocity of exogenous auxin transport in intact
      chilling-sensitive and chilling-resistant plants.
AB  - The velocity of exogenous indol-3yl-acetic acid ([1-(14)C]IAA) transport from the
      apical buds of intact pea, sunflower and cotton plants was determined from 0.5
      degrees  C to 47 degrees  C. The minimum temperature at which transport occurred
      varied from 2 degrees  C (pea and sunflower) to 7 degrees  C (cotton). Above
      these temperatures the velocity of transport increased steadily to maxima near 44
      degrees  C in all three species. Further increase in temperature resulted in a
      complete cessation of transport, suggesting a sudden high-temperature breakdown
      of the auxin transport system. Temperature coefficients (Q10) for transport
      velocity calculated from Arrhenius plots were low (1.36 to 1.41 between 15
      degrees  C and 30 degrees  C).Arrhenius plots for the chilling-sensitive cotton
      and sunflower plants exhibited abrupt discontinuities at 14.6 degrees  C and 8.7
      degrees  C respectively. An Arrhenius plot for the chilling-resistant pea
      exhibited no such discontinuity over the whole temperature range at which
      transport occurred. 

PMID- 24318335
TI  - Chemical and ultrastructural evidence that waxes associated with the suberin
      polymer constitute the major diffusion barrier to water vapor in potato tuber
      (Solanum tuberosum L.).
AB  - Combined gas chromatography-mass spectrometry showed that C21, C23, and C25 n
      alkanes accumulated in the suberized layers during wound healing of cores of
      potato tuber tissue. Treatment (10 min) of freshly-cut tissue with
      trichloroacetate (TCA), an inhibitor of fatty-acid chain elongation, severely
      inhibited accumulation of hydrocarbons and fatty alcohols associated with the
      suberized layer in the wound healing tissue (maximum inhibition at 4 mM) but had
      very little effect on the deposition of the major aliphatic components of the
      suberin polymer. This preferential inhibition of wax synthesis resulted in severe
      inhibition of the development of diffusion resistance of the tissue to water
      vapor. These results strongly indicate that the waxes associated with the suberin
      polymer, rather than the polymer itself, consitute the major diffusion barrier
      formed during wound healing. Electron-microscopic examination showed that
      inhibition of wax synthesis by TCA disrupted the formation of the lamellar
      structure of suberin specifically by preventing the formation of the light bands.
      This evidence strongly suggests that the light bands in the suberin complex are
      composed of waxes. 

PMID- 24318336
TI  - Calcium gradients in tip growing plant cells visualized by chlorotetracycline
      fluorescence.
AB  - With chlorotetracycline (CTC)-fluorescence a tip-to-base Ca(2+) gradient is
      visualized in all tested, tip-growing plant cells: pollen tubes of Lilium
      longiflorum, root hairs of Lepidium sativum, moss caulonema of Funaria
      hygrometrica, fungal hyphae of Achlya and in the alga Acetabularia mediterranea.
      The fluorescence gradients in the different species vary in intensity and
      extension. Sometimes a punctate mobile CTC-fluorescence, in the size range of
      mitochondria, is observed. Bursting cells lose their fluorescence rapidly,
      indicating a cytoplasmic localization of the gradient. Only in Acetabularia is
      the wall also fluorescent with CTC. The results are interpreted as evidence for a
      general role of a calcium gradient in tip growth. 

PMID- 24318337
TI  - Sensitivity of Commelina stomata to abscisic acid.
AB  - Stomata of Commelina leaves pre-opened by incubation in moist air were found to
      close within 30 min when supplied with abscisic acid (ABA) via the transpiration
      stream. Radioactive ABA had similar effects, but allowed the distribution of the
      compound within the leaf to be measured and correlated with stomatal movements to
      give estimates of the sensitivity of Commelina stomata. On a whole-leaf basis,
      less than 163 fmol ABA per mm(2) leaf area were present at the time of complete
      stomatal closure. This was close to other published estimates. By taking
      epidermal (14)C measurements, however, it was possible to increase the accuracy
      of the estimate on the assumption that only ABA present in the epidermis was
      physiologically active. Thus, less than 235 amol ABA for stomatal complex were
      present at complete closure, and statistically significant narrowing of the
      stomatal aperture had occurred when between 12.6 and 45.4 amol per complex were
      present. The distribution of ABA within the epidermal tissue after transpiration
      stream application was studied using microautoradiography, and the compound
      appeared to have accumulated within the stomatal complex. 

PMID- 24318338
TI  - Lysine metabolism in a barley mutant resistant to S(2-aminoethyl)cysteine.
AB  - Lysine and S(2-aminoethyl)cysteine (AEC) metabolism were investigated in normal
      barley (Hordeum vulgare L. cv. Bomi) and a hemozygous recessive AEC-resistant
      mutant (R906). Feedback regulation of lysine and threonine synthesis from [(14)C]
      acetate was unimpaired in plants of the mutant 3 d after germination. Seeds of
      Bomi and R906 contained similar total amounts of lysine, threonine, methionine
      and isoleucine. Concentrations of these amino acids in the soluble fraction of
      plants grown 6 d without AEC were also similar. The concentration of AEC in R906
      plants was less than in the parent variety when both were grown in the presence
      of 0.25 mM AEC for 6 d. The uptake of [(3)H]AEC and [(3)H]lysine by roots of R906
      was, respectively, 33% and 32% of that by Bomi roots whereas the uptake of these
      compounds into the scutellum was the same in both the mutant and its parent. The
      uptake of [(3)H]leucine and its incorporation into proteins was also the same in
      Bomi and R906 plants. These results suggest that a transport system specific for
      lysine and AEC but not leucine is altered or lost in roots of the mutant R906.
      AEC is incorporated into protein and this could be the reason for inhibition of
      growth rather than action as a false-feedback inhibitor of lysine biosynthesis. 

PMID- 24318339
TI  - Changes in the composition of cotton fibre cell walls during development.
AB  - Purified cell walls, prepared from cotton fibres (Gossypium arboreum L.) at
      different growth stages, were subjected to successive extractions to give pectic,
      hemicellulosic, and alpha-cellulosic fractions. The protein content and sugars
      obtained after hydrolysis of the total cell walls and of the various fractions
      were quantitatively estimated. The amount of protein in the fibre cell walls from
      one ovule reached a maximum value at the end of the elongation growth, decreased,
      and then reached a second maximum at the end of the secondary wall deposition.
      The absolute amounts of fucose, galactose, mannose, rhamnose, arabinose, uronic
      acid, and non-cellulosic glucose residues all reached a maximum at the end of the
      primary wall formation or at the beginning of the secondary wall formation. Only
      the absolute amounts of xylose and of the cellulosic glucose residues increased
      until the end of the fibre development. Most conspicuous was the decrease in the
      absolute amounts of non-cellulosic glucose and of arabinose residues during the
      secondary wall formation, possibly indicating a turnover of at least some of the
      hemicellulosic wall material. 

PMID- 24318340
TI  - Soluble and microsomal glutatione S-transferase activities in pea seedlings
      (Pisum sativum L.).
AB  - Epicotyl and primary leaves of pea seedlings (Pisum sativum L., var. Alaska) were
      found to contain soluble and microsomal enzymes catalyzing the addition of
      glutathione to the olefinic double bond of cinnamic acid. Glutathione S-cinnamoyl
      transfer was also obtained with enzyme preparations from potato slices and cell
      suspension cultures of parsley and soybean.The pea transferases had pH-optima
      between pH 7.4 and 7.8 Km-values were 0.1-0.4 mM and 1-4 mM for cinnamic acid and
      glutathione, respectively. V-values were between 2-15 nmol mg(-1) protein x
      min.Chromatography on Sephacryl S-200 indicated that the soluble pea glutathione
      S-cinnamoyl transferase activity existed in molecular weight forms of 37,000,
      75,000, and 150,000. The glutathione-dependent cleavage of the herbicide
      fluorodifen was catalyzed by a different soluble enzyme activity which eluted in
      molecular weight positions of 47,000 and/or 82,000.The microsomal fraction from
      pea primary leaves also catalyzed the conjugation of the carcinogen
      benzo[alpha]pyrene with glutathione. 

PMID- 24318341
TI  - Auxin-induced ethylene biosynthesis in subapical stem sections of etiolated
      seedlings of Pisum sativum L.
AB  - 1-Aminocyclopropane-1-carboxylic acid (ACC) stimulated the production of ethylene
      in subapical stem sections of etiolated pea (cv. Alaska) seedlings in the
      presence and absence of indole-3-acetic acid (IAA). No lag period was evident
      following application of ACC, and the response was saturated at a concentration
      of 1 mM ACC. Levels of endogenous ACC paralleled the increase in ethylene
      production in sections treated with different concentrations of IAA and with
      selenoethionine or selenomethionine plus IAA. The IAA-induced formation of both
      ACC and ethylene was blocked by the rhizobitoxine analog aminoethoxyvinylglycine
      (AVG). Labelling studies with L-[U-(14)C]methionine showed an increase in the
      labelling of ethylene and ACC after treatment with IAA. IAA had no specific
      effect on the incorporation of label into S-methylmethionine or homoserine. The
      specific radioactivity of ethylene was similar to the specific radioactivity of
      carbon atoms 2 and 3 of ACC after treatment with IAA, indicating that all of the
      ethylene was derived from ACC. The activity of the ACC-forming enzyme was higher
      in sections incubated with IAA than in sections incubated with water alone. These
      results support the hypothesis that ACC is the in-vivo precursor of ethylene in
      etiolated pea tissue and that IAA stimulates ethylene production by increasing
      the activity of the ACC-forming enzyme. 

PMID- 24318342
TI  - Aggregation pheromone of the deodar weevll,Pissodes nemorensis (Coleoptera:
      Curculionidae): Isolation and activity of grandisol and grandisal.
AB  - The bark weevilPissodes nemorensis, a pest of pines and exotic cedars in the
      southeastern United States, utilizes a male-produced aggregation pheromone. The
      presumed pheromone components, grandisol (cis-2-isopropenyl-1
      methylcyclobutaneethanol) and its corresponding aldehyde, grandisal, were
      isolated from extracts of male volatiles and male hindguts. A field test in
      northern Florida showed that the combination of grandisol, grandisal, and slash
      pine (Pinus elliottii) bolts acted synergistically to attract large numbers of
      male and femaleP. nemorensis. These components deployed in various paired
      combinations were not as attractive as the tripartite mixture. There was no
      evidence that flying weevils were attracted to unbaited pine bolts. The
      aggregation pheromone forP. nemorensis appears to be similar to that of a
      parapatric sibling species,P. approximatus. 

PMID- 24318343
TI  - Alarm response to venom by social waspsPolistes exclamans andP. fuscatus
      (Hymenoptera: Vespidae).
AB  - The venoms ofPolistes exclamans andP. fuscatus elicit alarm behavior and attract
      attacking wasps. The response is not species specific, for both hetero- and
      conspecific venoms elicit similar responses in both species. A test in a wind
      tunnel provided no support for the hypothesis that alarmed wasps release an alarm
      pheromone on the nest. 

PMID- 24318344
TI  - Synthesis of highly active juvenile hormone analogs, juvocimene I and II, from
      the oil of sweet basil,Ocimum basilicum L.
AB  - Juvocimene I and II are potent juvenile hormone mimics isolated from the
      essential oil of sweet basil,Ocimum basilicum L. The structures given by the
      formula I and II have been confirmed by synthesis withtrans-beta-ocimene andp
      methoxycinnamyl chloride. Biological activity of the natural and synthetic
      juvocimenes was found to be identical. 

PMID- 24318345
TI  - Identification of trail pheromone of the antTetramorium caespitum L.
      (Hymenoptera: Myrmicinae).
AB  - The trail pheromone of the antTetramorium caespitum L. is a 70?30 mixture of 2,5
      dimethylpyrazine and 3-ethyl-2, 5-dimethylpyrazine. The average total amount of
      the two pyrazines present in the poison vesicle was found to be 3.9 ng per ant,
      of which 2.7 +/- 0.4 ng is 2,5-dimethylpyrazine and 1.15 +/-0.25 ng is 3-ethyl
      2,5-dimethylpyrazine. The pyrazines constitute only 0.03% of the volume of the
      poison vesicle but account for the whole of the trail-following activity. A 70?30
      mixture of the respective pyrazines evoked the highest activity in artificial
      trail-following tests. 

PMID- 24318346
TI  - Variability in accumulation of proanthocyanidins (condensed tannins) in needles
      of Douglas-fir (Pseudotsuga menziesii) following long-term budworm defoliation.
AB  - Long-term defoliation by budworms was associated with higher levels of soluble
      proanthocyanidins in the current year needles of Douglas-fir trees. The
      proanthocyanidin contents of needles from defoliated Douglas-fir trees were
      considerably more variable than those levels of undefoliated ones. The increased
      mean and variability of proanthocyanidin levels following defoliation may have
      interesting ecological consequences for Douglas-fir and its defoliators. 

PMID- 24318347
TI  - Search for potent attractants of onion flies.
AB  - Of various chopped vegetables tested,Allium spp. high in propyl-containing alkyl
      sulfides (e.g.,cepa group) caught the most onion flies in trapping tests in the
      field. Fly catches to chopped onion increased with bait quantity. Attractancy of
      chopped onion changed dramatically during aging in the field; catch increased
      over the first few days, peaked at ca. fivefold over fresh material by 3-5 days,
      and then declined sharply. This age-dependent increase in attraction was not seen
      for garlic (known to have antimicrobial properties) nor with chopped onion mixed
      with chopped garlic. These data suggested that attraction of onion flies to
      onions was strongly influenced by microbial activity associated with decomposing
      onions. The bacteriumKlebsiella pneumoniae was identified as a major colonizer of
      onions maximally attractive to onion flies. This increased attraction is not due
      to the previously reported microbially produced volatiles ethyl acetate and
      tetramethyl pyrazine. 

PMID- 24318348
TI  - Eucalyptus oils in larvae of gum emperor moth,Antheraea eucalypti.
AB  - The ether-soluble portion of the foregut fluid from the larvae ofAntheraea
      eucalypti (Saturniidae) was found to contain traces (0.1-0.2%) of isoprenoids.
      The isoprenoids were those that were major components of the oils from the leaves
      of theEucalyptus species on which the larvae fed and were also soluble in the
      foregut fluid. This observation demonstrated that these larvae did not sequester
      the leaf oils in their foregut or use them for defense. The compositions of the
      oils, which were steam-distilled from the bodies and feces of the larvae, were
      identical with those of the oils from the leaves of the host trees. This fact
      implied that the volatile components of the leaf oils had not been metabolized
      and had no effect on the growth or feeding of the larvae, at least on the
      twoEucalyptus species examined. In order to explain the coevolution ofA.
      eucalypti andEucalyptus species, components of the leaf oils were suggested to
      serve the function of an ovipositional attractant to the female moths. 

PMID- 24318349
TI  - Antifeedant activity of quassinoids.
AB  - The antifeedant activity of 13 quassinoids of different structural types has been
      studied against the Mexican bean beetle (Epilachna varivestis Mulsant) 4th instar
      larvae and the southern armyworm (Spodoptera eridania Crawer) 5th instar larvae.
      All quassinoids tested displayed significant activity against the Mexican bean
      beetle and, thus, do not reveal a simple structure-activity relationship. Five
      quassinoids were active against the southern armyworm. Interestingly, four of
      these-bruceantin (I), glaucarubinone (VI), isobruceine A (VIII), and
      simalikalactone D (XI)-possess the required structural features for
      antineoplastic activity. The noncytotoxic quassin (X) is an exception; it is
      active against both pests. 

PMID- 24318350
TI  - Responses by king snakes (Lampropeltis getulus) to chemicals from colubrid and
      crotaline snakes.
AB  - Four litters of king snakes (Lampropeltis getulus), a snake-eating species, were
      tested for responses to chemicals from colubrid and crotaline snakes. King snakes
      presented with swabs rubbed against the dorsal skin of living snakes and with
      swabs treated with methylene chloride extracts of shed snake skins tongue-flicked
      more to swabs from a northern copperhead (Agkistrodon contortrix), a crotaline,
      than to swabs from some colubrid snakes or to blank swabs. Six out of 10 king
      snakes in one litter attacked and attempted to ingest swabs treated with snake
      skin chemicals, implicating these chemicals as feeding stimuli for these
      ophiophagous snakes. Ingestively naive king snakes presented with plain air and
      snake odors in an olfactometer tongue-flicked more to snake odors. This study and
      others suggest that crotaline and colubrid snakes can be distinguished by
      chemical cues. 

PMID- 24318351
TI  - Interference of sonic communication and mating in leafhopperAmrasca devastans
      (distant) by certain volatiles.
AB  - Mating between the two sexes in the leafhopperAmrasca devastans was inhibited by
      cineole vapors surrounding host plant leaves bearing the insects. There was a
      decline in the percentage of pairs mating and mated females fertilized. The
      vapors were not toxic and did not prevent the insects' arrival on the leaves. The
      cineole vapors inhibited the mating chiefly by interfering with the surface
      mediated sonic communication between the sexes. The inhibition of mating was
      chemical specific since other volatiles, e.g., citral, were not as effective as
      cineole. Exposure to cineole vapors resulted in a decline in the sexual response
      of the females to the sonic signals of the male. 

PMID- 24318352
TI  - New sex attractants for 35 tortricid and 4 other lepidopterous species, found by
      systematic field screening in The Netherlands.

PMID- 24318353
TI  - Tissue is the issue in transient ischemic attack and stroke.

PMID- 24318354
TI  - The effect of Se-deficient diet on gene expression of inflammatory cytokines in
      chicken brain.
AB  - Selenium (Se) plays an important role in the brain development, function, and
      degeneration, nutritional encephalomalacia is closely related with dietary Se in
      avian. However, there is little evidence on the relationship between inflammation
      and encephalomalacia in avian and the mechanism which Se regulates the
      inflammatory response in brain tissues remains to be unclear. The present paper
      describes the effects of Se-deficient granulated diet on one transcription factor
      nuclear factor kappaB and four pro-inflammatory cytokines-tumor necrosis factor,
      cyclooxygenase2, inducible nitric oxide synthase and Prostaglandin E synthase
      mRNA expression in the chicken brain tissues associated encephalomalacia. One
      hundred male chickens (1 day old; Weiwei Co. Ltd., Harbin, China) were divided
      into two groups (50 chickens per group). The expression levels in the brain
      tissues (cerebral gray matter, cerebral white matter, marrowbrain, cerebellum,
      thalamus and brain stem) were determined by real-time PCR on days 15, 25, 35, 45,
      and 55, respectively. The results showed the productions of pro-inflammatory
      mediators were increased following Se-deficiency. These data indicate the
      correlations between nutritional encephalomalacia and inflammatory response and
      the activity of inflammatory response in chicken brain may be induced by Se
      deficiency. 

PMID- 24318355
TI  - Cellular localization and developmental changes of the different isoforms of
      divalent metal transporter 1 (DMT1) in the inner ear of rats.
AB  - Divalent metal transporter 1 (DMT1) is generally considered to be the major
      transmembrane protein responsible for the uptake of a variety of divalent
      cations. Four isoforms of DMT1 have been identified in mammalian cells encoded by
      a single gene that differ both in their N- and C-terminal sequences with two mRNA
      isoforms possessing an iron response element (IRE) motif downstream from the stop
      codon on the message. Two distinct promoter sites regulate production of the 1A
      or 1B isoforms (translation starts at exon 2) for both the +IRE or -IRE species
      of the transporter resulting in the generation of four distinct configurations of
      this protein. Prior studies from our laboratory using cochlear organotypic
      cultures isolated from postnatal day three rats (P3) have demonstrated that Mn
      causes significant and selective damage to sensory hair cells and auditory nerve
      fibers and spiral ganglion neurons in a time and concentration dependent manner.
      Since DMT1 plays a critical role in controlling the uptake of a variety of
      essential and toxic metals into the cochlea, we compared the distribution and
      developmental changes of the 1A, +IRE and -IRE isoforms in rat inner ear. Results
      reveal that all three isoforms of DMT1 are selectively expressed in different
      cell populations within the cochlea and, additionally, demonstrate their cellular
      and subcellular distribution changes with development. 

PMID- 24318356
TI  - The heterogeneity of ovarian cancer.
AB  - Ovarian cancer carries the worst prognosis of all gynecological malignancies.
      This is mainly due to its resistance against commonly used cytostatic drugs as
      well as the lack of a screening method for its detection at an early stage. Both
      basic and translational research have shown over the past decades that ovarian
      cancer as a medical term includes several types of tumors with different
      phenotypes, molecular biology, etiology, tumor progression, and even different
      prognosis. In this issue of Archives of Gynecology and Obstetrics, J. Dietel
      presents a review article about novel findings of the etiopathogenesis of ovarian
      cancer and the role that fallopian tubes may play. He also outlines the implied
      clinical consequences. Here, we give a brief overview of the heterogeneity of
      ovarian cancer to introduce the topic. 

PMID- 24318357
TI  - Music and medicine.

PMID- 24318358
TI  - Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and
      colorectal cancer risk-results from the EPIC cohort study.
AB  - Coffee and tea contain numerous antimutagenic and antioxidant components and high
      levels of caffeine that may protect against colorectal cancer (CRC). We
      investigated the association between coffee and tea consumption and CRC risk and
      studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes
      involved in the metabolization of caffeine. Data from 477,071 participants (70.2%
      female) of the European Investigation into Cancer and Nutrition (EPIC) cohort
      study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and
      decaffeinated) coffee and tea consumption was assessed with dietary
      questionnaires. Cox proportional hazards models were used to estimate adjusted
      hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect
      modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested
      case-control set of 1,252 cases and 2,175 controls. After a median follow-up of
      11.6 years, 4,234 participants developed CRC (mean age 64.7 +/- 8.3 years). Total
      coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06,
      95% CI 0.95-1.18) or subsite cancers, and no significant associations were found
      for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96,
      95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea
      consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk
      compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2
      activity, which suggests that caffeine metabolism does not affect the link
      between coffee and tea consumption and CRC risk. This study shows that coffee and
      tea consumption is not likely to be associated with overall CRC. 

PMID- 24318360
TI  - Acceptable symptom state after surgery for femoroacetabular impingement compared
      with total hip arthroplasty.
AB  - The aim of the study was to examine whether patients undergoing total hip
      arthroplasty (THA) are better able to accept a given level of pain and disability
      than patients undergoing surgery for femoro-acetabular impingement (FAI). Before
      surgery, 417 THA and 162 FAI patients completed the Oxford Hip Score (OHS). At 12
      months follow-up (FU), they were requested to complete the OHS again, rate the
      global treatment outcome, and state whether their symptom state was acceptable.
      Preoperatively, THA had worse (p<0.001) OHS scores than FAI. At 12 months, 99%
      THA and 86% FAI patients reported various degrees of improvement. The proportions
      of patients perceiving notable improvement and considering their current state
      acceptable were higher (p<0.0001) in THA (95-99%) than FAI (66-70%) and THA had
      greater (p<0.0001) improvements in OHS scores than FAI. The mean OHS score of the
      patients perceiving notable improvements at follow-up did not differ (p>0.05)
      between THA and FAI groups. Higher "success rates" in THA than FAI are not due to
      a better acceptance of pain and disability, because the OHS of patients
      considering their current state to be acceptable was similar for both groups. The
      difference is simply the result of more THA than FAI patients actually achieving
      an acceptable status after surgery. 

PMID- 24318359
TI  - A TRAF2 binding independent region of TNFR2 is responsible for TRAF2 depletion
      and enhancement of cytotoxicity driven by TNFR1.
AB  - Tumor Necrosis Factor (TNF) interacts with two receptors known as TNFR1 and
      TNFR2. TNFR1 activation may result in either cell proliferation or cell death.
      TNFR2 activates Nuclear Factor-kappaB (NF-kB) and c-Jun N-terminal kinase (JNK)
      which lead to transcriptional activation of genes related to cell proliferation
      and survival. This depends on the binding of TNF Receptor Associated Factor 2
      (TRAF2) to the receptor. TNFR2 also induces TRAF2 degradation. In this work we
      have investigated the structural features of TNFR2 responsible for inducing TRAF2
      degradation and have studied the biological consequences of this activity. We
      show that when TNFR1 and TNFR2 are co-expressed, TRAF2 depletion leads to an
      enhanced TNFR1 cytotoxicity which correlates with the inhibition of NF-kB. NF-kB
      activation and TRAF2 degradation depend of different regions of the receptor
      since TNFR2 mutants at amino acids 343-349 fail to induce TRAF2 degradation and
      have lost their ability to enhance TNFR1-mediated cell death but are still able
      to activate NF-kB. Moreover, whereas NF-kB activation requires TRAF2 binding to
      the receptor, TRAF2 degradation appears independent of TRAF2 binding. Thus, TNFR2
      mutants unable to bind TRAF2 are still able to induce its degradation and to
      enhance TNFR1-mediated cytotoxicity. To test further this receptor crosstalk we
      have developed a system stably expressing in cells carrying only endogenous TNFR1
      the chimeric receptor RANK-TNFR2, formed by the extracellular region of RANK
      (Receptor activator of NF-kB) and the intracellular region of TNFR2.This has made
      possible to study independently the signals triggered by TNFR1 and TNFR2. In
      these cells TNFR1 is selectively activated by soluble TNF (sTNF) while RANK-TNFR2
      is selectively activated by RANKL. Treatment of these cells with sTNF and RANKL
      leads to an enhanced cytotoxicity. 

PMID- 24318362
TI  - Dynamics of femoral bone remodelling in well fixed total hip arthroplasty. A 20
      year follow-up of 20 hips.
AB  - The aim of our study was to investigate the dynamics of cortical thinning around
      well fixed cemented Muller straight stems without osteolysis at different time
      periods during long term follow-up. We investigated patients operated on for
      osteoarthritis with a cemented Muller straight stem, all with more than 15 years
      follow-up and no radiological signs of osteolysis. Cortical thinning in 20 THA
      hips (19 patients) followed for a mean of 20 (16 to 22) years was measured
      medially and laterally at six levels from the first postoperative, five, 10 years
      and the last follow-up x-rays. Sixty percent of observed cortical thinning
      occurred during the first five postoperative years, which was more evident
      proximally. We conclude that significantly greater cortical bone loss occurs
      around cemented Muller straight stems during the first five years, than is seen
      subsequently. We feel that this is a non-pathological process mainly related to
      the Muller straight stem. 

PMID- 24318363
TI  - Is total hip arthroplasty a successful and safe procedure in Jehovah's Witnesses?
      Mean five-year results.
AB  - Total hip arthroplasty (THA) can be challenging in Jehovah's Witnesses because of
      the potential for blood loss. Because these patients will not accept blood
      transfusions, multiple strategies to prevent blood loss have been developed. The
      purpose of this study was to report implant survivorship, clinical outcomes,
      radiographic outcomes, morbidity, and mortality of Jehovah's Witnesses undergoing
      primary THA. Databases from two institutions were reviewed to identify 53
      patients (55 hips) who were Jehovah's Witnesses and had a primary total hip
      arthroplasty. There were 27 women and 26 men who had a mean age of 63 years
      (range 35-94 years), and a mean follow-up of 63 months (range 24-120 months). All
      Jehovah's Witnesses had a comprehensive perioperative blood management strategy
      employed by a coordinated medical and surgical team. Mean post-operative Harris
      Hip Scores were 86 points, and implant survivorship was 97%. There were two
      aseptic revisions for osteolysis and component loosening. There were no
      mortalities, and three minor surgical and two minor medical complications
      occurred during the study. Excellent clinical outcomes were found for Jehovah's
      Witness undergoing total hip arthroplasty using a comprehensive blood management
      protocol. We believe that the use of a specialised blood management protocol
      involving a team approach to preoperative evaluation, appropriate anaesthesia,
      and surgical and postoperative management was responsible for minimising
      complications. Total hip arthroplasty is safe and efficacious in this patient
      group if proper preoperative safeguards are utilised. 

PMID- 24318364
TI  - Circumferential reconstruction of severe acetabular labral damage using hamstring
      allograft: surgical technique and case series.
AB  - INTRODUCTION: With excessive acetabular coverage, such as coxa profunda or
      protrusio, contact between the femoral neck and acetabular rim cause direct
      damage to the labrochondral junction, and indirect edge loading from a levering
      effect which may result in hip arthrosis. Arthrosis may be delayed or avoided by
      addressing the overcoverage and restoring mechanical function of the labrum. We
      describe four cases of adjunctive complete acetabular labral replacement for
      circumferential, irreparable labral injury using fresh frozen semitendinous
      allografts through surgical hip dislocation. MATERIALS AND METHODS: Over a two
      year period four patients (age range: 20 to 47 years) underwent surgical hip
      dislocation to address femoroacetabular impingement with rim trimming, femoral
      osteochondroplasty, and labral reconstruction. Pre- and postoperative patient
      reported outcomes were assessed by Oxford Hip Score (OHS), Hip Outcome Score
      (HOS), and Global Treatment Outcome (GTO) score. Disease progression was graded
      using AP pelvic radiographs and arthroMR. RESULTS: The average LCE correction was
      18o (range 7-25o), achieving an average LCE of 33o (range 32-35) postoperatively.
      Using protected weight bearing all trochanteric osteotomies healed within six
      weeks after surgery. OA did not progress in any hips. Mean OHS and HOS scores
      improved 6.3 and 19.8 at one-year follow up. All four patients reported good
      results according to the GTO. There were two adverse events that resolved and did
      not affect outcome. SUMMARY AND CONCLUSIONS: Despite complex deformities and
      preexisting cartilage and labrum wear in this young cohort, three of four
      patients reported significant functional improvement after treatment of this rare
      condition. Preliminary experience with circumferential labral reconstruction
      using hamstring allografts is promising, although long-term data needs to be
      established.

PMID- 24318365
TI  - Expression of an endoglucanase from Tribolium castaneum (TcEG1) in Saccharomyces
      cerevisiae.
AB  - Insects are a largely unexploited resource in prospecting for novel cellulolytic
      enzymes to improve the production of ethanol fuel from lignocellulosic biomass.
      The cost of lignocellulosic ethanol production is expected to decrease by the
      combination of cellulose degradation (saccharification) and fermentation of the
      resulting glucose to ethanol in a single process, catalyzed by the yeast
      Saccharomyces cerevisiae transformed to express efficient cellulases. While S.
      cerevisiae is an established heterologous expression system, there are no
      available data on the functional expression of insect cellulolytic enzymes for
      this species. To address this knowledge gap, S. cerevisiae was transformed to
      express the full-length cDNA encoding an endoglucanase from the red flour beetle,
      Tribolium castaneum (TcEG1), and evaluated the activity of the transgenic product
      (rTcEG1). Expression of the TcEG1 cDNA in S. cerevisiae was under control of the
      strong glyceraldehyde-3 phosphate dehydrogenase promoter. Cultured transformed
      yeast secreted rTcEG1 protein as a functional beta-1,4-endoglucanase, which
      allowed transformants to survive on selective media containing cellulose as the
      only available carbon source. Evaluation of substrate specificity for secreted
      rTcEG1 demonstrated endoglucanase activity, although some activity was also
      detected against complex cellulose substrates. Potentially relevant to uses in
      biofuel production rTcEG1 activity increased with pH conditions, with the highest
      activity detected at pH 12. Our results demonstrate the potential for functional
      production of an insect cellulase in S. cerevisiae and confirm the stability of
      rTcEG1 activity in strong alkaline environments. 

PMID- 24318366
TI  - Prospective non-randomized comparison of open versus laparoscopic transabdominal
      preperitoneal (TAPP) inguinal hernia repair under different anesthetic methods.
AB  - PURPOSE: To compare prospectively open vs. laparoscopic transabdominal
      preperitoneal (TAPP) inguinal hernia repair performed under different anesthetic
      methods. METHODS: A total of 175 patients scheduled for unilateral inguinal
      hernia repair were assigned to one of the following groups: (i) open repair under
      local anesthesia, (ii) open repair under regional anesthesia, (iii) open repair
      under general anesthesia, and (iv) TAPP under regional anesthesia. Immediate
      postoperative pain was the main outcome measured. Short- and long-term
      complications and the degree of patient satisfaction were also assessed. RESULTS:
      Transabdominal preperitoneal repair under regional anesthesia yielded the lowest
      pain scores, whereas open repair under general anesthesia yielded the highest
      pain scores (P < 0.05). Open repair under local or general anesthesia had a lower
      urinary retention incidence than the spinal groups (P < 0.05). Chronic pain
      incidence was lower for the TAPP group (P 0.003). There were no differences in
      other short- and long-term complications. CONCLUSION: Transabdominal
      preperitoneal repair under spinal anesthesia proved superior to open repair
      performed under different types of anesthesia in terms of immediate (24-h)
      postoperative pain. The method of anesthesia might have contributed more to this
      favorable outcome than the surgical technique itself, but at the cost of a high
      urinary retention incidence. The incidence of chronic pain was lower after TAPP
      repair.

PMID- 24318367
TI  - Multifocality in testicular germ cell tumor (TGCT): what is the significance of
      this finding?
AB  - PURPOSE: The aim of the study is to determine the association between
      multifocality and the pathological features of testicular germ cell tumors and
      its clinical implication. METHODS: Orchiectomy specimens from 254 consecutive
      patients with testis cancer between 2003 and 2013 were included. Multifocality
      was defined as a distinct tumor focus of cluster of malignant cells > 0.5 mm and
      separable from the main tumor mass. Univariate logistic regression analysis was
      performed to evaluate the association between multifocality and other
      pathological features. Multivariate logistic regression analyses were carried out
      to identify potential predictive factors of multifocality for clinical stages II
      III and the pathological stage >= pT2. RESULTS: Median patient age was 33 years
      (range 19-70). Multifocality was identified in 58 (22.83 %) orchiectomy
      specimens. Subjects with multifocality had larger primary tumor lesions (3.7 vs.
      3.0 cm; p < 0.05). No association was found between histology and multifocality
      (p = 0.95). On univariate logistic regression analysis, multifocality was not
      significantly associated with all pathological features. On multivariate logistic
      regression analysis, multifocality was not demonstrated to be an adverse
      pathological feature of clinical stages II-III (p = 0.23) or pathological stage
      >= pT2 (p = 0.30) when included in a model with tumor size >= 4 cm and rete
      testis invasion in seminoma tumor and neither of clinical stages II-III (p =
      0.36) or pathological stage >= pT2 (p = 0.20) when included in a model with
      lymphovascular invasion and percentage of embrional cancer >= 50 % in non
      seminoma ones. CONCLUSION: Multifocality should not be considered an adverse
      pathological feature in patients with testis cancer, independently to
      histological subtypes.

PMID- 24318368
TI  - Acute kidney injury after radical gastrectomy: a single center study.
AB  - OBJECTIVES: To investigate the incidence of acute kidney injury (AKI) and
      identify risk factors for AKI in patients who undergo radical gastrectomy.
      METHODS: This study included 536 patients underwent radical gastrectomy. Primary
      outcome was AKI, defined as a >= 50 % increase in serum creatinine relative to
      baseline during the first three postoperative days. Secondary outcomes were
      duration of hospitalization and all-cause hospital mortality within 30 days after
      radical gastrectomy. RESULTS: A total of 37 (6.9 %) patients developed
      postoperative AKI. Age, body mass index (BMI), presence of hypertension,
      hyperlipidemia, poor blood glucose control, and preoperative higher cystatin C
      were associated with increased frequency of AKI. By multivariable analyses, the
      independent risk factors for AKI were age, BMI, hypertension, hyperlipidemia, and
      preoperative cystatin C. CONCLUSIONS: Postoperative AKI is not infrequent after
      radical gastrectomy. Age, BMI, hypertension, hyperlipidemia, and preoperative
      cystatin C are independently associated with increased risk of postoperative AKI.

PMID- 24318371
TI  - Analysis of the heat-shock protein pattern during somatic embryogenesis of
      carrot.
AB  - The pattern of proteins synthesized by carrot cells after heat-shock was analyzed
      by SDS-polyacrylamide gel electrophoresis. A study was made of the time of
      appearance and disappearance of the heat-shock bands and a comparison was made of
      the heat-shock proteins present in cell extracts obtained from cell suspensions,
      callus, protoplasts and the different stages of somatic embryogenesis.From this
      comparison a number of differences and hence of stage-specific markers could be
      seen. This type of analysis was also carried out in the presence of alpha
      amanitin in order to get information on the type of control of heat-shock protein
      synthesis. It turned out that in all stages after the initial globular stage,
      alpha-amanitin does not alter the heat-shock protein pattern suggesting pre
      existence of the relative mRNA's. 

PMID- 24318369
TI  - Calcification of the thoracic aorta determined by three-dimensional computed
      tomography predicts cardiovascular complications in patients undergoing
      hemodialysis.
AB  - PURPOSE: In patients on dialysis, the most common cause of death is
      cardiovascular disease. This is caused, at least in part, by excessive vascular
      calcification. Studies that have examined coronary calcification have been
      published, but these measurements require expensive equipment. Here, we used
      computed tomography to determine aortic calcification and evaluated these data as
      prognostic markers for cardiovascular disease. METHODS: Computed tomography with
      contrast medium was performed on 49 patients undergoing hemodialysis (29 males
      and 20 females; average age, 68.9 +/- 11.0 years). A calcification score (CS) was
      defined as the ratio of the volume of vascular calcification to the volume of the
      thoracic aorta. All patients were monitored for cardiovascular end points, which
      included cerebral infarction or hemorrhage, myocardial infarction,
      electrocardiographic, or echocardiographic abnormalities that suggested
      myocardial ischemia, cardiac surgery, leg amputation, and hospitalization or
      death due to heart failure. RESULTS: Patients were followed for 3 years, with 12
      patients reaching the end point. Both high CS (p = 0.007) and male gender (p =
      0.009) were significantly associated with cardiovascular events. In contrast,
      events were not related to age, dialysis duration, diabetes mellitus, smoking
      status, low-density lipoprotein cholesterol level, pulse-wave velocity, maximum
      intima-media thickness of the carotid artery wall, systolic blood pressure, or
      left ventricular hypertrophy. Multiple logistic regression analysis revealed that
      a high baseline CS was a significant predictor for cardiovascular events (p <
      0.05). CONCLUSIONS: Calcification of the thoracic aorta determined by three
      dimensional computed tomography predicts cardiovascular complications in patients
      on hemodialysis.

PMID- 24318372
TI  - Contitions for optimal growth of a PSTV-infected potato cell suspension and
      detection of viroid-complementary longer-than-unit-length RNA in these cells.
AB  - A suspension culture from potato spindle tuber viroid (PSTV)-infected cells of
      the wild type potato (Solanum demissum) has been established, which is a suitable
      model system for studying PSTV replicationin vivo. The conditions for rapid
      growth of these cells and for permanent extensive viroid biosynthesis within them
      are described. Biosynthesis of PSTV in the potato cells was demonstrated by(32)P
      incorporation into nucleic acids and their subsequent electrophoretic analysis on
      polyacrylamide gels. Under optimum culture conditions the amount of(32)P
      orthophosphate incorporation into PSTV reached 10% of that incorporated into the
      2 M LiCl-soluble cellular RNA. (+)PSTV and its complementary form, i.e. (-)PSTV
      were identified after their electrophoretic separation on polyacrylamide and
      agarose gels by molecular hybridization. This analysis revealed the presence of
      six high molecular weight(-)PSTV species, which are possibly multimers of the
      unit length(+)PSTV molecule consisting of 359 nucleotides. 

PMID- 24318373
TI  - Modulation by abscisic acid and S-2-aminoethyl-L-cysteine of alpha-amylase mRNA
      in barley aleurone cells.
AB  - The changes in the levels of alpha-amylase mRNA is barley aleurone layers in
      response to addition of plant growth regulators have been studied using a cloned
      alpha-amylase cDNA as the hybridization probe. An increase in gibberellic acid
      (GA) concentration in the incubation medium from 10(-9) M to 10(-6) M results in
      a progressive increase in alpha-amylase mRNA concentration in the aleurone cells.
      Detectable levels of alpha-amylase mRNA appear in the aleurone cells as early as
      1 h after addition of GA. The concentration of this mRNA increases for several
      hours and then declines rapidly. Abscisic acid (ABA) and the amino acid analog S
      2-aminoethyl-L-cysteine (AEC) suppress the GA-mediated induction of alpha
      amylase. These compounds appear to affect the level of alpha-amylase mRNA in
      aleurone cells as measured byin vitro translation assays and by analysis of RNA
      blots with alpha-amylase cDNA probes. It is concluded that the regulation of
      alpha-amylase gene expression by ABA is at the level of transcription. Further, a
      protein factor appears to be required in addition to GA for transcription of
      alpha-amylase genes. 

PMID- 24318374
TI  - Sequence interrelationships of the subunits of vicilin from pea seeds.
AB  - Serological studies and comparison of N-terminal amino acid sequences with the
      amino acid sequence deduced from a cDNA clone have been used to establish the
      sequence relationships between the subunits of the pea seed storage protein,
      vicilin. Subunits smaller than Mr~50 000 (i.e., Mr 34 000, 30 000, 25 000, 18
      000, 14 000, 13 000 and 12 000) show extensive homology with molecules within
      Mr~50 000 group. Both the sequencing and serological data confirm earlier
      evidence from studies on vicilin synthesisin vivo andin vitro which indicated
      that the vicilin subunits smaller than Mr~50 000 arose by endoproteolytic
      cleavage of parent molecules within the Mr~50 000 group. Cleavage in different Mr
      50 000 parent molecules containing either one or both of two susceptible
      processing sites accounts for the formation of all the vicilin subunits smaller
      than Mr~50 000, with the possible exception of the Mr34 000 polypeptide. The
      position of these sites in the putative parents were defined by reference to a
      complete amino acid sequence deduced from the sequence of DNA complementary to
      mRNA for one member of the Mr~50 000 group. 

PMID- 24318375
TI  - Identification of a multigene family for small heat shock proteins in soybean and
      physical characterization of one individual gene coding region.
AB  - When soybean seedlings are tranferred from 28 to 40  degrees  C, a heat shock
      (hs) response is elicited. This is characterized by the synthesis of a new set of
      proteins (hs-proteins) and by cessation of normal protein synthesis (8). At the
      level of poly(A)mRNA, a new class of highly abundant RNAs appears which encodes a
      group of hs-proteins in the low molecular weight range of 15-18 kD (11). The
      classification of these proteins/genes into several sub-classes is based on a
      complex sequence relationship for class I protein/genes.This was confirmed by
      both the complexity and the similarity of southern blot hybridization patterns of
      genomic DNA digests with class I cDNA-probes. Genomic DNA clones (obtained from
      lambda-libraries by screening with cDNA-probes) for the class I gene 1968 showed
      cross hybridization with all other class I cDNA-probes. Higher specificity of
      gene/protein correlation was obtained by variation of hybridization criteria. The
      specificity of cDNA clone 1968 for the genomic DNA clone lambdahs68-7 was
      demonstrated by thermal stability of hybridization at 55  degrees  C and 65 
      degrees  C in 50% formamide compared to other cross-reacting probes. The
      correlation of clone 1968 with a specific hs-protein was obtained by temperature
      dependent release of hybrid selected hs-mRNAs at 50, 60, 70 and 85  degrees  C
      followed byin vitro translation and two-dimensional gel analysis. The coding
      regions of hs-genes on genomic DNA clones were mapped by R-loop formation. The
      position of R-loops was mapped relative to certain restriction sites on subclones
      of lambdahs68-7 DNA. The polarity of hs-genes was determined by attaching
      phiX174RF-DNA 'labels' to the 3' poly(A)-tails of the mRNAs of R-loops. 

PMID- 24318376
TI  - Synthesis of the large subunit of ribulose-1,5-bisphosphate carboxylase in anin
      vitro partially definedE. coli system.
AB  - Thein vitro DNA- or RNA-directed synthesis of the large subunit (LS) of spinach
      chloroplast ribulose-1,5-biphosphate carboxylase (RuP2C) has been examined in a
      highly definedE. coli transcription-translation system. Spinach chloroplast DNA,
      RNA and recombinant plasmids containing the spinach chloroplast LS gene (rbcL)
      have been used as templates in thein vitro system and a quantitative assay has
      been developed to measure LS formation. Thein vitro formed product contains
      formylmethionine at the N-terminal position and sediments primarily as a monomer.
      There is no detectable enzymatic activity associated with thein vitro product. To
      determine where theE. coli RNA polymerase used in these systems initiates, we
      have examined the transcripts produced by this enzymein vitro. Measurements of
      run-off transcripts indicate thatE. coli RNA polymerase initiates at the same
      position on the gene as is seenin vivo. In addition, the complete nucleotide
      sequence of therbcL gene including previously unsequenced 3' and 5' flanking
      regions has been determined. The sequence agrees, except at two nucleotide
      positions, with previously published sequencing data for this gene (Zurawski, G,
      Perrot, B, Bottomley, W, Whitfeld, PR, 1981. Nucleic Acids Res. 9:3251-3270). 

PMID- 24318377
TI  - Psychosocial distress among young breast cancer survivors: implications for
      healthcare providers.
AB  - Breast cancer (BC) experiences foster serious psychosocial problems among young
      survivors. Previous studies have repeatedly discussed younger age as a factor
      that puts women with BC at higher risk of psychosocial distress. Although most BC
      survivors receive the necessary information from healthcare providers on
      treatment options and procedures at diagnosis, they often fail to receive support
      and guidance after acute treatment has completed in dealing with the possible
      physical, emotional, social, and psychological effects of cancer. This article
      discusses common psychosocial problems experienced by young BC survivors, such as
      issues related to interpersonal relationships, sexuality, fertility, and
      employment. In particular, it examines influences of the Japanese sociocultural
      background on young survivors' distress and considers the clinical implications
      for Japanese healthcare. The importance of integrating psychosocial care with
      routine oncology care cannot be overemphasized.

PMID- 24318378
TI  - Four frontiers.

PMID- 24318379
TI  - The Adam and Eve syndrome.
AB  - CONCLUSION: The concept of divine forgiveness is incomprehensible to most, since
      it involves principles that defy rational interpretation on the level of human
      cognition. As a result, individuals, and especially those who present themselves
      for treatment, find themselves caught up in a repetition of self-judgment and
      selfpunishment, which is a reenactment of the original sin and the disobedience
      encountered in the Garden of Eden. It can be pointed out to patients that this
      continuous, repetitious acting out of the functions of self-judgment and
      selfpunishment represents the worst sin of all-the original sin in which the
      power and authority of God are usurped and assumed, resulting eventually in a
      denial of God along with symptoms that are often incapacitating. When these
      functions are returned to God, punishment can be expected to be much less severe
      and intense, because of the nature and characteristics of divine forgiveness.

PMID- 24318380
TI  - The amoral character of our attitudes about death: Some implications.

PMID- 24318381
TI  - Mature religious behavior: A psychological perspective and its implications.

PMID- 24318383
TI  - Psychiatry in a restless world.

PMID- 24318382
TI  - The healing of the dying.

PMID- 24318384
TI  - Dreaming, religion, and health.
AB  - Dreaming has been presented as a universal human phenomenon. Ancient as
      contrasted with modern peoples have viewed the dream as a mysterious, powerful,
      yet comprehensible experience within the context of their theological world view.
      After hypothesizing that our contemporary state of alienation and fragmentation
      is related to our tendency to dichotomize experience into real and unreal, I
      reviewed psychoanalytic and depth psychological approaches to dreaming,
      concluding that an ego-analytic-depth approach is most compatible with
      theological perspectives. Following a review of empirical dream research
      supporting the hypothesis that dream process is related to health, I presented a
      structural model linking six ego and theologically analogous constructs:
      integration-creation, synthesis-dependence, selection-choice,
      cognitionincarnation, regulation-redemption, and anticipation-eschatology.
      Finally, I presented a patient's dream, suggesting how the model might be applied
      for a more comprehensive view of the dreaming process. 

PMID- 24318385
TI  - "...As thyself".

PMID- 24318386
TI  - Clinical and translational potential of MRI evaluation in knee osteoarthritis.
AB  - Magnetic resonance imaging (MRI) has become an increasingly important imaging
      technique in osteoarthritis (OA) research, and is widely used in the ongoing
      endeavor to understand the pathogenesis of OA and to develop structure and
      disease-modifying OA drugs. MRI offers semiquantitative, quantitative and
      compositional evaluation of knee OA, and enables visualization of tissues that
      are not seen by radiography, including but not limited to cartilage, meniscus,
      bone marrow lesions, synovitis, and muscles. It is now recognized that contrast
      enhanced MRI enables more accurate evaluation of synovitis than MRI without
      contrast. Because of its ability to visualize multiple pain-related tissue
      pathology in three dimensions, MRI is the best modality for imaging of OA. 

PMID- 24318387
TI  - Highly modular C(1) -symmetric chiral (P,N) ligands with a stereolabile P center:
      experimental and theoretical studies.
AB  - An improved synthesis of a novel class of bidentate (P,N) ligands is presented,
      the structures of which are characterized by three distinct elements of
      chirality. The stereoselective installation of the elements of central chirality
      (at the benzylic carbon and the phosphorus atom) depends on the size of the
      phosphorus substituent. Thermal inversion of the phosphorus center has been
      studied experimentally and further correlated by DFT calculations. The potential
      of these ligands and the role of the phosphorus atom in the asymmetric alpha
      arylation of aldehydes (Pd) and hydrogenation of allylic alcohols (Ir) have also
      been investigated. 

PMID- 24318388
TI  - Role of diet in host selection ofHeliothis virescens by parasitoidCampoletis
      sonorensis (Hymenoptera: Ichneumonidae).
AB  - Gas chromatographic analysis revealed that chemicals attractive toCampoletis
      sonorensis (Cameron), previously identified in cotton, were not present in wheat
      germ diet-rearedHeliothis virescens (F.) larvae. Diet-reared larvae fed cotton
      obtained the chemicals from cotton, with the consequence of enhanced kairomonal
      activity of the larvae and their frass toC. sonorensis. Parasitoids, presented a
      choice between cotton, cotton plus hosts, hosts alone, and control in an
      olfactometer, responded non-randomly, with the greatest number of responses to
      cotton plus hosts, and three times as many responses to cotton alone as to larvae
      alone. The role of the plant in the parasitoid-host relationship is discussed. 

PMID- 24318389
TI  - Revolving fraction collector for preparative capillary gas chromatography in the
      100-MUg to 1-ng range.
AB  - A gas chromatography fraction collector for use with capillary columns,
      consisting of an all-glass system with a revolving collector housing six
      capillary tubes, 100 * 1 mm (internal diameter), has been constructed and tested.
      The collector is cooled with solid CO2 and has a recovering efficiency of 50-75%
      in the 100-MUg to 1-ng range for compounds of different polarities and
      volatilities, exemplified by mono- and sesquiter-penes and long-chain esters. The
      technique has been used for fractionating blends of semiochemicals prior to
      microchemical reactions, spectroscopic analyses, and behavioral experiments. 

PMID- 24318390
TI  - Potential for evolution of resistance to pheromones: Interindividual and
      interpopulational variation in chemical communication system of pink bollworm
      moth.
AB  - After an extensive examination of the release rates and blend ratios of
      pheromonal components emitted by field-collected femalePectinophora gossypiella
      (Saunders), we find no evidence of resistance to pheromones applied to cotton
      fields to disrupt mating. Females from fields with 3-5 years of exposure to
      disruptant pheromones as well as those from fields with only minimal exposure to
      disruptant pheromones emitted (Z,Z)-7,11-hexadecadienyl acetate at a rate of ca.
      0.1 ng/min and (Z,E)7,11-hexadecadienyl acetate at ca. 0.06 ng/min. The ratio of
      pheromonal components was much less variable than the measured emission rate and
      was centered about a 61:39Z, Z to Z,E ratio. In contrast to the blend ratio
      emitted by females, the composition of the pheromonal blend used in monitoring
      populations and disrupting mating is centered about 50:50 Z,Z to Z.E. In general
      there was a remarkable consistency in the release rate and blend ratio among
      populations of females throughout southern California and those from a laboratory
      colony. It would appear that, although resistance to theP. gossypiella pheromone
      is still a very real possibility when it is used heavily in pest management as a
      mating disruptant, there are current agricultural practices and conditions which
      would hinder its development. 

PMID- 24318391
TI  - Iridoid glycosides and host-plant specificity in larvae of the buckeye
      butterfly,Junonia coenia (Nymphalidae).
AB  - Larvae of the buckeye,Junonia coenia (Nymphalidae) feed primarily on plants in
      four families: Scrophulariaceae, Plantaginaceae, Verbenaceae, and Acanthaceae.
      These plant families have in common the presence of a group of plant secondary
      compounds, the iridoid glycosides. Larvae were reared on three plant species and
      two artificial diets, one with and one without iridoid glycosides.Larvae grew
      poorly and had low survivorship on the artificial diet without iridoid
      glycosides, while growth and survival on the artificial diet with iridoid
      glycosides was comparable to that on plants. Choice tests using artificial diets
      with and without iridoid glycosides showed that larvae: (1) chose diets with
      iridoid glycosides (in the form of a crude extract or pure compound) over a diet
      without; (2) showed no preference between the diet with the crude extract and
      that with pure iridoid glycoside, and (3) preferred the artificial diet with
      ground leaves of the host plant,Plantago lanceolata, over the diet with pure
      iridoid glycosides. The artificial diet that larvae had been reared on prior to
      these tests had no effect on subsequent larval preferences in the choice tests. 

PMID- 24318392
TI  - Sex pheromone components of fall cankerworm moth,Alsophila pometaria : Synthesis
      and field trapping.
AB  - (Z,Z,Z,E)-3,6,9,11-Nonadecatetraene and (Z,Z,Z,Z)-3,6,9,11-nonadecatetraene, sex
      pheromone components ofAlsophila pometaria, were synthesized by stereoselective
      Wittig reactions and found to be spectroscopically and chromatographically
      identical to isolated natural material. Flight-tunnel bioassays and field
      trapping experiments confirmed that the two tetraenes together with (Z,Z,Z)-3,6,9
      nonadecatriene are sex pheromone components. While traps baited with either
      tetraene individually captured conspecific males in field-trapping experiments,
      addition of the triene, which captured no males by itself, to either tetraene
      resulted in synergistic responses. 

PMID- 24318393
TI  - Relative kairomonal activities of 2-acylcyclohexane-1,3-diones in eliciting
      oviposition behavior from parasiteNemeritis canescens (Grav.).
AB  - The relative activities of sixteen 2-acylcyclohexane-1,3-diones from the larval
      mandibular glands ofEphestia (=Anagasta) kuehniella Zeller in causing the
      parasiteNemeritis (=Venturia) canescens (Grav.) to make oviposition movements are
      reported. 

PMID- 24318394
TI  - Possible chemical basis for histocompatibility-related mating preference in mice.
AB  - High-resolution chromatographic profiles of urinary volatiles were quantitatively
      recorded and statistically evaluated for the female mice genetically differing in
      a small region of the major histocompatibility complex on the 17th chromosome.
      Both immature and estrogenized animals were evaluated. While there seem to be no
      specific volatile products of the histocompatibility genes, statistically
      significant differences were readily observed with the immature females of
      different haplotypes, involving the general range of secondary volatile
      metabolites. Their possible role in olfactory communication is discussed. 

PMID- 24318395
TI  - Repellent effect of volatile fatty acids of frass on larvae of german
      cockroach,Blattella germanica (L.) (Dictyoptera: Blattellidae).
AB  - Two- to 12-day-old larvae ofBlattella germanica are repelled by certain volatile
      fatty acids present in the frass. Propionic, isovaleric, and valeric acids are
      strongly repellent, isobutyric acid is slightly repellent, and acetic and butyric
      acids are without effect. These results are discussed in relation to control of
      population density. 

PMID- 24318396
TI  - Behavioral responses of elm bark beetles to baited and unbaited elms killed by
      cacodylic acid.
AB  - Diseased elms, treated with various doses of cacodylic acid in northwest England,
      became attractive to elm bark beetles (Coleoptera: Scolytidae). This attraction
      seemed to be independent of pheromone baits. However attractive the trees became,
      they were unsuitable to the beetles as breeding sites since significantly more
      beetles visited the trees than were stimulated to penetrate and attempt to breed.
      It seems as if colonization of trap trees by the bark saprophytePhomopsis oblonga
      following cacodylic acid treatment made the trees unsuitable to beetles for
      breeding. 

PMID- 24318398
TI  - Abstracts of the 3rd World Psoriasis & Psoriatic Arthritis Conference 2012:
      "Psoriasis-a global health challenge" : Stockholm, Sweden, June 27-July 1, 2012.

PMID- 24318397
TI  - Redundancy in a chemical signal: Behavioral responses of maleTrichoplusia ni to a
      6-Component sex pheromone blend.
AB  - The flight response of maleTrichoplusia ni was observed in a flight tunnel to a
      sex pheromone blend composed of six components:Z7-12?Ac, 12?Ac,Z5-12?Ac, 11
      12?Ac,Z7-14?Ac, and Z9-14?Ac. The number of males reaching a 3000-MUg source of
      this blend was > 95%, equal to that observed to female glands and significantly
      greater than with the previously identified two-component blend (Z7-12?Ac +
      12?Ac). In subtraction tests, all five-component blends, with the exception of
      the blend lacking the primary componentZ7-12?Ac, and several four-component
      blends elicited similar peak levels of upwind flight, source contacts, and
      hairpencil displays to that observed with the six-component blend. We
      characterize the substitution of certain minor components for one another as a
      form of redundancy in the chemical signal and suggest that it contributes to
      response specificity and signal recognition in males. The results also support
      the concept that the full blend of components acts as a unit to influence male
      behavior at all phases of the response. Individual minor components were not
      responsible for eliciting specific behaviors in the sequence. 

PMID- 24318401
TI  - Root hair length and rhizosheath mass depend on soil porosity, strength and water
      content in barley genotypes.
AB  - Selecting plants with improved root hair growth is a key strategy for improving
      phosphorus-uptake efficiency in agriculture. While significant inter- and intra
      specific variation is reported for root hair length, it is not known whether
      these phenotypic differences are exhibited under conditions that are known to
      affect root hair elongation. This work investigates the effect of soil strength,
      soil water content (SWC) and soil particle size (SPS) on the root hair length of
      different root hair genotypes of barley. The root hair and rhizosheath
      development of five root hair genotypes of barley (Hordeum vulgare L.) was
      compared in soils with penetrometer resistances ranging from 0.03 to 4.45 MPa
      (dry bulk densities 1.2-1.7 g cm(-3)). A "short" (SRH) and "long" root hair (LRH)
      genotype was selected to further investigate whether differentiation of these
      genotypes was related to SWC or SPS when grown in washed graded sand. In low
      strength soil (<1.43 MPa), root hairs of the LRH genotype were on average 25 %
      longer than that of the SRH genotype. In high-strength soil, root hair length of
      the LRH genotype was shorter than that in low-strength soil and did not differ
      from that of the SRH genotype. Root hairs were shorter in wetter soils or soils
      with smaller particles, and again SRH and LRH did not differ in hair length.
      Longer root hairs were generally, but not always, associated with larger
      rhizosheaths, suggesting that mucilage adhesion was also important. The root hair
      growth of barley was found to be highly responsive to soil properties and this
      impacted on the expression of phenotypic differences in root hair length. While
      root hairs are an important trait for phosphorus acquisition in dense soils, the
      results highlight the importance of selecting multiple and potentially robust
      root traits to improve resource acquisition in agricultural systems.

PMID- 24318402
TI  - The role of published information in reviewing conservation objectives for Natura
      2000 protected areas in the European Union.
AB  - Protected areas are designated to protect species and other features known to be
      present at the time of designation, but over time the information about the
      presence of protected species may change and this should call for a continued
      review of conservation objectives. Published scientific literature is one of the
      possible information sources that would trigger a review of conservation
      objectives. We studied how published data on new discoveries of protected animal
      species were taken into account by the nature conservation authorities in
      updating species lists of Natura 2000 sites in the European Union, which are the
      basis for conservation planning at the site-level. Over the period studied (2000
      2011) only 40 % of published new protected species records were recognized by the
      authorities. The two main reasons for this seem to be a reliance on other sources
      of information by authorities and the difficulty in finding relevant information
      in scientific papers. The latter is because published faunistic information is
      very fragmented among different journals, and often insufficient in details. We
      recommend better cooperation between authors, publishers, and nature conservation
      authorities in terms of information presentation, publishing policy, and a
      regular review of published information. 

PMID- 24318403
TI  - Impacts of transportation routes on landscape diversity: a comparison of
      different route types and their combined effects.
AB  - A comparison of different transportation route types and their combined effects
      on landscape diversity was conducted within Tiaoxi watershed (China) between 1994
      and 2005. Buffer analysis and Mann-Kendall's test were used to quantify the
      relationships between distance from transportation routes (railway, highway,
      national, and provincial road) and a family of landscape diversity parameters
      (Simpson's diversity index, Simpson's evenness index, Shannon's diversity index,
      and Shannon's evenness index). One-way ANOVA was further applied to compare
      influences from different route types and their combined effects. Five other
      landscape metrics (patch density, edge density, area-weighted mean shape index,
      connectance index, and Euclidean nearest neighbor distance) were also calculated
      to analyze the associations between landscape diversity and landscape pattern
      characteristics. Results showed that transportation routes exerted significant
      impacts on landscape diversity. Impact from railway was comparable to that from
      highway and national road but was more significant than that from provincial
      road. The spatial influential range of railway and national road was wider than
      that of highway and provincial road. Combined effects of routes were nonlinear,
      and impacts from different route types were more complex than those from the same
      type. The four landscape diversity metrics were comparably effective at the
      buffer zone scale. In addition, landscape diversity can be alternatively used to
      indicate fragmentation, connectivity, and isolation at route buffer scale. This
      study demonstrates an applicable approach to quantitatively characterize the
      impacts from transportation routes on landscape patterns and has potential to
      facilitate route network planning. 

PMID- 24318404
TI  - Computational fluid dynamics analysis of the pump parameters in the helical flow
      pump.
AB  - The helical flow pump (HFP) was invented to develop a total artificial heart at
      the University of Tokyo in 2005. The HFP consists of the multi-vane impeller
      involving rotor magnets, a motor stator and pump housing having double-helical
      volutes. To investigate the characteristics of the HFP, computational fluid
      dynamics analysis was performed. Validation of the computational model was
      performed with the data of the actual pump. A control computational model in
      which the vane area corresponded approximately to that of the actual pump was
      designed for the parametric study. The parametric study was performed varying the
      vane height, vane width and helical volute pitch. When the vane height was varied
      from 0.5 to 1.5 times that of the control computational model, the H-Q (pressure
      head vs. flow) and efficiency curves were translated in parallel with the vane
      height. When the vane height was two and three times that of the control
      computational model, the profile of these curves changed. From the results, the
      best proportion for the vane was considered to be a vane height between 1.5 and 2
      times the vane width. The effect of vane width was not very strong compared to
      that of the vane height. A similar tendency in vane height was observed by
      varying the helical volute pitch. The best helical volute-pitch size is
      considered to be between 1.5 and 2 times the vane width. Although further study
      is necessary to determine the best values for these parameters, the
      characteristics of the pump parameters in the HFP could be approximately
      clarified. 

PMID- 24318405
TI  - The hip labrum reconstruction: indications and outcomes--a systematic review.
AB  - PURPOSE: With further understanding of the function and the importance of the hip
      labrum, greater attention has been paid to preserve and repair the damaged
      labrum. Hip labrum reconstruction has been described to optimize hip preservation
      when the labrum is deficient. This systematic review aimed to explore and
      identify the reported indications and outcomes in patients who undergo labral
      reconstruction of the hip joint. METHODS: The electronic databases EMBASE,
      MEDLINE, and PubMed were searched for all available dates up to July 2013.
      Further hand search of the reference sections of the included studies was done.
      Two reviewers searched, screened, and evaluated the included studies for data
      quality using the Methodological Index for Non-Randomized Studies (MINORS) Scale.
      Data were also abstracted in duplicate, and agreement and descriptive statistics
      are presented. RESULTS: There were 5 eligible studies (3 case series, 1
      prospective cohort, and 1 retrospective chart review) with a total of 128
      patients, and an average 11/16 quality on the MINORS score included in this
      review. All patients were diagnosed with femoroacetabular impingement and
      underwent labral reconstruction. Ninety-four patients were assessed at follow-up
      (73.4 % survivorship) between a reported mean range of 10 and 49 months. There
      was variability between the studies with regard to the graft types utilized (ilio
      tibial band, Gracilis tendon, Ligamentum teres), surgical approaches [open (18.7
      %) vs. arthroscopic (81.3 %)], and the reported outcome measures. Overall,
      improvement was observed in the patient-reported outcomes and functional scores
      (mHHS, HOS, UCLA, NASH, and SF-12). The failure rate or conversion to THA rate in
      all available patients was 20 %. The most common indication for labrum
      reconstruction was a young, active patient with minimal arthritis and non
      salvageable or deficient labrum. Other indications included instability, pain,
      and hypotrophic dysfunctional labrum. CONCLUSION: Based on the current available
      evidence, hip labrum reconstruction is a new technique that shows short-term
      improvement in patient-reported outcomes and functional scores post-operatively.
      The main indication for reconstruction was a deficient labrum due to previous
      surgical excision or irreparable tears in young patients with no significant
      arthritis. Long-term follow-up results with higher quality studies are still
      lacking based on this review.

PMID- 24318406
TI  - Herpes simplex virus encephalitis is a trigger of brain autoimmunity.
AB  - In 5 prospectively diagnosed patients with relapsing post-herpes simplex
      encephalitis (HSE), N-methyl-D-aspartate receptor (NMDAR) antibodies were
      identified. Antibody synthesis started 1 to 4 weeks after HSE, preceding the
      neurological relapse. Three of 5 patients improved postimmunotherapy, 1
      spontaneously, and 1 has started to improve. Two additional patients with NMDAR
      antibodies, 9 with unknown neuronal surface antibodies, and 1 with NMDAR and
      unknown antibodies, were identified during retrospective assessment of 34 HSE
      patients; the frequency of autoantibodies increased over time (serum, p=0.004;
      cerebrospinal fluid, p=0.04). The 3 retrospectively identified NMDAR antibody
      positive patients also had evidence of relapsing post-HSE. Overall, these
      findings indicate that HSE triggers NMDAR antibodies and potentially other brain
      autoimmunity.

PMID- 24318407
TI  - Epigenetics and ocular diseases: from basic biology to clinical study.
AB  - Epigenetics is an emerging field in ophthalmology and has opened a new avenue for
      understanding ocular development and ocular diseases related to aging and
      environment. Epigenetic mechanisms, including DNA methylation, histone
      modifications, chromatin remodeling, and deployment of non-coding RNAs, result in
      the heritable silencing of gene expression without any change in DNA sequence.
      Accumulating evidence suggests a potential link between gene expression,
      chromatin structure, non-coding RNAs, and cellular differentiation during ocular
      development. Disruption of the balance of epigenetic networks could become the
      etiology of several ocular diseases. Here, we summarized the current knowledge
      about epigenetic regulatory mechanisms in ocular development and diseases.

PMID- 24318408
TI  - Histological damage of colonic epithelium is associated with clinical severity
      and outcome in colectomized critically Ill patients.
AB  - BACKGROUND: Severe intestinal mucosal damage and organ failure has been
      associated in experimental models. Our purpose was to determine whether there is
      any association between histopathological findings and postoperative mortality
      among ICU patients undergoing emergency colectomies for various illnesses.
      METHODS: In a retrospective case control study, total colectomy specimens from 50
      patients in a mixed ICU were analysed: 18 had sepsis, 11 vascular operations, and
      21 Clostridium difficile colitis. Overall thickness, the width of epithelial
      defects, and presence of cryptal damage were assessed. Extent of necrosis and
      amount of neutrophils were separately evaluated in the layers of the colonic
      wall. Clinical features, including sequential organ failure assessment (SOFA)
      scores and survival, were registered. RESULTS: The histopathological findings for
      the three clinical entities were similar, except for the abundance of
      characteristic pseudomembranes in the Clostridium group. Mucosal height (maximum)
      showed a negative correlation with SOFA score on admission (rho = -0.296, P =
      0.037), and with preoperative blood lactate level (rho = -0.316; P = 0.027). The
      nonsurvivors had wider enterocyte defects (60 vs. 40.8, P = 0.002) and more
      severe crypt damage (61 vs. 27 %; P = 0.024) than the survivors. CONCLUSIONS: The
      histopathological damage involves all layers of the colon wall among ICU patients
      being largely similar in sepsis, C. difficile infection, and ischemia after
      vascular operations. Mucosal epithelial damage is associated with clinical
      severity of the illness and mortality.

PMID- 24318409
TI  - Ruptured AAA: suitability for endovascular repair is associated with lower
      mortality following open repair.
AB  - OBJECTIVES: Perioperative mortality of open repair of ruptured abdominal aortic
      aneurysms (rAAA) remains unacceptably high: 30-day mortality ~ 40 %. This study
      aimed to assess, quantify, and determine the consequences of anatomic suitability
      for endovascular repair of rAAA. DESIGN: A retrospective analysis of the
      prospectively maintained database identified patients with rAAA. METHODS:
      Preoperative CT scans were assessed for anatomic suitability for emergency EVAR
      and precluding factors recorded. Demographic information was collected and
      analysed for all patients. RESULTS: A total of 141 patients underwent open
      surgical repair of rAAA. Forty-six patients had preoperative CT scans suitable
      for reconstruction. Morphological measurements indicated that 41 % would have
      been anatomically suitable for EVAR. Suitability was associated with lower
      mortality rates than unsuitability: 0, 11, and 20 % (24 h, 30 days, and 1 year
      respectively) versus 11, 33, and 59 % (statistically significant at 1 year; p =
      0.02). The groups were comparable excepting diabetes incidence, which was higher
      in those suitable for EVAR (p = 0.003). CONCLUSIONS: A minority of patients with
      ruptured AAA are anatomically suitable for EVAR. Anatomical suitability appears
      to identify patients at low risk from open surgery. Whether this is due to
      technically less demanding open surgery is unknown. This may be resolved by the
      IMPROVE trial results, which are eagerly awaited.

PMID- 24318410
TI  - Continuous absorbable intradermal sutures yield better cosmetic results than
      nonabsorbable interrupted sutures in open appendectomy wounds: a prospective,
      randomized trial.
AB  - BACKGROUND: Acute appendicitis is the most common reason for abdominal surgery in
      young adults and children. Open appendectomy is still the treatment often chosen
      because it is simple, safe, and effective. Our aim was to study whether cosmetic
      results of appendectomy wounds are better after using continuous absorbable
      intradermal (A) sutures compared with wound closure with interrupted
      nonabsorbable (NA) sutures. METHODS: A total of 206 adult patients with
      clinically suspected appendicitis were allocated to the study and prospectively
      randomized into two wound-closure groups: the interrupted NA suture group and the
      A suture group. Of these, 193 patients with sufficient data were invited to the
      outpatient clinic for cosmetic analysis. Cosmetic results were evaluated after a
      median of 14 months. For subjective scar assessment, the Vancouver scar scale,
      the patient and observer scar assessment scale (POSAS), and a visual analog scale
      (VAS) were used. Objective evaluation was carried out by measuring surface area,
      average width, and estimated concentration change (ECC) of hemoglobin and melanin
      in the scar using spectrocutometry. For statistical analyses we used the Mann
      Whitney test and Student's t test. RESULTS: Both objective and subjective
      analyses showed better cosmetic results for absorbable intradermal suturing. The
      difference between the two groups was statistically significant as regards POSAS
      in both patient (p = 0.032) and observer scales (p = 0.001), and VAS (p = 0.002).
      Scar surface area was significantly smaller in group A than in group NA (p =
      0.002). ECC measurements showed higher values for melanin in group NA than in
      group A (p = 0.034). CONCLUSION: Continuous intradermal absorbable suturing
      yields a better cosmetic result than interrupted nonabsorbable suturing in lower
      abdominal transverse appendectomy.

PMID- 24318412
TI  - Isomorphic sclerotic-type cutaneous chronic graft-versus-host disease: report and
      review of chronic graft-versus-host disease in a cutaneous immunocompromised
      district.
AB  - BACKGROUND: Patients who have received a hematopoietic cell transplantation can
      develop graft-versus-host disease (GVHD). The liver, the gastrointestinal tract,
      and/or the skin can be affected by GVHD. Chronic sclerotic-type cutaneous GVHD
      can occur at sites of repetitive skin friction. PURPOSE: To describe isomorphic
      sclerotic-type GVHD and review chronic GVHD appearing in a cutaneous
      immunocompromised district. METHODS: The clinical features of a 74-year-old man
      with mantle cell lymphoma who developed chronic sclerotic-type cutaneous GVHD
      localized to the waistband area-which had been exposed to repetitive skin injury
      after a second hematopoietic cell transplantation are reported. Using the PubMed
      database, an extensive literature search was performed on chronic GVHD. CASE
      REPORT AND REVIEW: The cutaneous immunocompromised district is an area of skin
      whose local effective immunity has been altered, thereby permitting the
      development of a dysimmune reaction, infection, or tumor at the site. A cutaneous
      isomorphic response refers to a disease-associated skin lesion occurring at the
      site of physical injury that is morphologically similar to the existing
      condition. Cutaneous chronic GVHD can occur at sites of repetitive skin trauma as
      an isomorphic response. The patient developed sclerotic-type GVHD in a cutaneous
      area that had previously experienced repeated irritation, friction, and pressure.
      Isomorphic sclerotic-type GVHD-in either the waistband area or brassiere area or
      both-has also been observed in other patients. In addition, cutaneous chronic
      GVHD has been described not only at the location of a previous, unrelated, and
      healed skin disease as an isotopic response, but also at the cutaneous site of
      earlier exposure to radiotherapy or ultraviolet radiation as an isoradiotopic
      response. CONCLUSION: Sclerotic and nonsclerotic skin lesions of chronic GVHD can
      occur not only as an isomorphic response, but also as either an isotopic response
      or an isoradiotopic response in a cutaneous immunocompromised district.

PMID- 24318411
TI  - Laparoscopic Roux-en-Y gastric bypass is effective and safe in over 55-year-old
      patients: a comparative analysis.
AB  - BACKGROUND: Controversy exists regarding the effectiveness and safety of
      laparoscopic Roux-en-Y gastric bypass (LRYGB) in elderly patients. We evaluated
      our outcomes of LRYGB in patients aged >= 55 years. METHODS: A total of 549
      consecutive patients underwent LRYGB as primary operation and 132 were >= 55
      years old. Patients were divided in two groups: group <55 years comprised 417
      patients, with mean age (+/- SD) of 41.15 +/- 8.47 years; group >= 55 years
      comprised 132 patients, with mean age of 59.43 +/- 3.81 years. Mean preoperative
      body mass index was 47.01 +/- 7.47 and 46.21 +/- 7.47 respectively, whereas mean
      excess weight loss percent (EW%) was 88.06 +/- 30.28 and 84.86 +/- 29.87 %. Early
      morbidity (30 days) and outcomes at 6, 12, and 24 months follow-up were
      evaluated. RESULTS: Significant difference was found in operative time (84.19 +/-
      29.05 vs. 90.89 +/- 30.95 min, p = 0.03). One conversion to open procedure
      occurred in group <55 years, whereas three occurred in group >= 55 years (p =
      0.04). Intraoperative complications occurred in 22 patients (5.27 %) in group <55
      years versus 19 in group >= 55 years (14.39 %), which was statistically
      significant (p = 0.001). One case of death occurred in the younger group. Overall
      postoperative morbidity rate was 18.7 % in group <55 years and 25.76 % in group
      >= 55 years, with no significant difference (p = 0.08). Mean EWL% at 12 months in
      group <55 years was 65.95.05 +/- 26.96 versus 62.61 +/- 41.78 in group >= 55
      years, whereas at 24 months it was 65.08 +/- 29.68 versus 64.48 +/- 18.44 with no
      significant difference between the groups (p = 0.51; p = 0.92). CONCLUSIONS:
      LRYGB for patients >= 55 years achieves outcomes and complications rates
      comparable to the younger population. Patients should not be denied bariatric
      surgery for the age alone.

PMID- 24318413
TI  - Long-Term Cost-Effectiveness Analysis of Etanercept and Adalimumab for Plaque
      Psoriasis not Associated with Arthritis.
AB  - INTRODUCTION: Pharmacoeconomic studies examining the cost-effectiveness of
      biological agents to treat moderate-to-severe psoriasis in real-life clinical
      practice are scarce. The aim of this study was to assess the efficiency, in terms
      of incremental cost-effectiveness, of etanercept and adalimumab in a real
      clinical setting. METHODS: Direct and indirect costs were assessed from a Spanish
      societal perspective in a historical hospital cohort of patients with moderate-to
      severe psoriasis attending a tertiary referral hospital over a 1-year period. The
      data examined included drug-related variables, use of health-care resources,
      transportation and work productivity losses. Effectiveness was measured as the
      proportion of patients achieving a reduction of at least 75% with respect to the
      baseline value for the Psoriasis Area Severity Index (PASI 75) during the first
      52 weeks of treatment. RESULTS: No statistically significant differences in
      effectiveness between etanercept (n = 135) and adalimumab (n = 48) were found
      (PASI 75 80% vs. 85.7%; RR = 1.07 [0.90, 1.27]; RRA = 5.7 [-8.9, 20.2]; p =
      0.943). There were no significant differences in total cost per patient with
      etanercept as compared to adalimumab (14,843.73 +/- 6,178.98 <euro> vs. 15,405.91
      +/- 9,106.50 <euro>; p = 0.768). CONCLUSION: Under conditions of daily clinical
      practice in our hospital, total health-care costs associated with the treatment
      of moderate-to-severe psoriasis with etanercept appear to be equivalent to those
      with adalimumab in the first year of treatment.

PMID- 24318414
TI  - Psoriasis and psycho-dermatology.
AB  - INTRODUCTION: Psoriasis is a common, long-term skin condition associated with
      high levels of psychological distress and considerable life impact. The impact of
      psoriasis, beyond the skin, is often not recognised and under-treated. METHODS:
      This paper explores the relationship between psychological distress and psoriasis
      including reference to the 'brain-skin access'. The life impact of psoriasis is
      discussed and pharmacological interventions which affect distress associated with
      psoriasis and psychological interventions are reviewed. Evidence from peer
      reviewed journals and controlled trials inform the text. RESULTS: Psoriasis has a
      profound impact on mental health and well-being which is under-recognised by
      clinicians. The sympathetic adrenal medullary axis and hypothalamic pituitary
      adrenal axis are likely to be involved in the onset of psoriasis and there may
      also be an effect from inflammation in the skin on the central release of
      corticotrophin-releasing hormone. Psoriasis can be stigmatising and may affect
      all aspects of life including relationships, employment, social life and leisure
      activities. There is some evidence for psychological interventions being
      effective in the management of distress associated with psoriasis and psoriasis
      itself. Studies, however, have used disparate outcomes and methods and largely
      involve low numbers of patients. There is very limited access to psychological
      support for the patients with psoriasis despite evidence of high levels of
      psychological distress and considerable life impact. CONCLUSIONS: Psoriasis is a
      long-term skin condition associated with high levels of distress and considerable
      life impact, both of which are under-recognised. Routine screening for distress
      with access to effective treatment is required. There is a need for high-quality
      studies to assess the effect of psychological intervention in patients with
      psoriasis both to inform guidance and facilitate the provision of effective
      psychological support services.

PMID- 24318415
TI  - Hydroxychloroquine-associated hyperpigmentation mimicking elder abuse.
AB  - BACKGROUND: Hydroxychloroquine may result in cutaneous dyschromia. Older
      individuals who are the victims of elder abuse can present with bruising and
      resolving ecchymoses. PURPOSE: The features of hydroxychloroquine-associated
      hyperpigmentation are described, the mucosal and skin manifestations of elder
      abuse are reviewed, and the mucocutaneous mimickers of elder abuse are
      summarized. CASE REPORT: An elderly woman being treated with hydroxychloroquine
      for systemic lupus erythematosus developed drug-associated black and blue
      pigmentation of her skin. The dyschromia was misinterpreted by her clinician as
      elder abuse and Adult Protective Services was notified. The family was eventually
      cleared of suspected elder abuse. A skin biopsy of the patient's dyschromia
      confirmed the diagnosis of hydroxychloroquine-associated hyperpigmentation.
      CONCLUSION: Hyperpigmentation of skin, mucosa, and nails can be observed in
      patients treated with antimalarials, including hydroxychloroquine. Elder abuse is
      a significant and underreported problem in seniors. Cutaneous findings can aid in
      the discovery of physical abuse, sexual abuse, and self-neglect in elderly
      individuals. However, medication-associated effects, systemic conditions, and
      accidental external injuries can mimic elder abuse. Therefore, a complete medical
      history and appropriate laboratory evaluation, including skin biopsy, should be
      conducted when the diagnosis of elder abuse is suspected.

PMID- 24318416
TI  - Triple-Blind, Prospective, Internally Controlled Comparative Study Between
      AbobotulinumtoxinA and OnabotulinumtoxinA for the Treatment of Facial Rhytids.
AB  - INTRODUCTION: OnabotulinumtoxinA (ONA; Botox, Allergan, Irvine, CA) was
      discovered for cosmetic use in the mid-1980s for which it was FDA approved in
      April 2002. AbobotulinumtoxinA (ABO; Dysport, Valeant Pharmaceuticals
      International, Inc, Montreal, Quebec) was FDA approved in April 2009 for
      therapeutic and esthetic uses. The most recent studies make a comparison between
      the two formulations; however, information is still lacking in comparison
      studies. In this study, we compare efficacy and safety of a single treatment of
      two preparations of botulinum toxin A in patients with moderate to severe rhytids
      in the glabellar and crow's feet areas. METHODS: A total of 85 patients with
      moderate to severe wrinkles in either the glabellar or crow's feet area, or both,
      were given a single injection on day 0, with ABO and ONA injected on opposite
      sides of the face. Follow-up assessments were done at 2 weeks, 1 month, 3 months,
      4 months, and 5 months. The study end points were onset of action, change in
      degree of wrinkles, patient satisfaction, duration of effect, and adverse
      effects. RESULTS: Results of onset of improvement with ABO vs. ONA in the
      glabellar and crow's feet regions show higher percentage of patients with earlier
      onset improvement with ABO. Evaluator assessment showed ABO lasted longer after 3
      months in a significant number of patients in both areas, 83% with ABO vs. 48%
      with ONA at 4 months in the glabellar area, and 65% with ABO vs. 47% with ONA at
      4 months in the crow's feet area. CONCLUSION: Time to improvement showed earlier
      onset and longer duration of improvement in a higher percentage of individuals
      with ABO when compared with ONA. ABO provides a safe and effective alternative in
      a dose ratio of 2.5:1 and 3:1 in the glabellar and crow's feet area,
      respectively.

PMID- 24318417
TI  - Vulval Crohn's disease in childhood.
AB  - Vulval involvement in Crohn's disease (CD) is rare, particularly in children. The
      clinical features include erythema, edema, ulceration, and labial skin tags. The
      authors present two cases of children with vulval CD. In both cases, marked
      labial edema was the presenting feature. In one patient the immunomodulator
      tacrolimus ointment 0.03% was used with success. In the second patient control
      was achieved with intralesional triamcinolone in combination with systemic
      metronidazole. 

PMID- 24318418
TI  - Combined reduced-antigen content tetanus, diphtheria, and acellular pertussis
      (tdap) vaccine-related erythema nodosum: case report and review of vaccine
      associated erythema nodosum.
AB  - BACKGROUND: Vaccination programs reduce the morbidity and mortality of
      diphtheria, pertussis, and tetanus. Erythema nodosum is a reactive erythema that
      can be associated with infections, drugs, and many conditions. The new onset of
      erythema nodosum after receiving vaccination is uncommon. PURPOSE: Combined
      reduced-antigen content tetanus, diphtheria, and acellular pertussis (Tdap)
      vaccine-associated erythema nodosum is described and the reports of vaccine
      related erythema nodosum are summarized. METHODS: The clinical features of a 39
      year-old woman who developed erythema nodosum after receiving Tdap vaccine are
      reported. Using the PubMed database, an extensive literature search was performed
      on erythema nodosum, vaccine, and vaccination. RESULTS: Tdap, the most commonly
      used booster vaccine against tetanus, diphtheria, and pertussis, is well
      tolerated in all age groups. Local injection-site reactions are the most common
      adverse events, whereas headache, fatigue, gastrointestinal symptoms, and fever
      are the most frequent systemic events. Erythema nodosum has not previously been
      reported in patients who have received Tdap vaccine. The patient developed
      erythema nodosum within 48 h after receiving Tdap vaccine; her symptoms cleared
      and nearly all skin lesions resolved within 2 weeks after initiating oral
      treatment with ibuprofen, fexofenadine, and prednisone. Vaccine-associated
      erythema nodosum has previously been reported following vaccination for cholera,
      hepatitis B, human papillomavirus, malaria, rabies, small pox, tuberculosis, and
      typhoid. CONCLUSION: Vaccine-associated erythema nodosum is uncommon. Erythema
      nodosum occurring after Tdap vaccination is a rare, yet potential, adverse
      effect.

PMID- 24318419
TI  - Increased ALK1 copy number and renal cell carcinoma-a case report.
AB  - There have been recent reports of a rare variant of renal cell carcinoma
      associated with upregulation of the anaplastic lymphoma kinase gene (ALK) arising
      as a consequence of chromosomal translocations. The tumours were described as
      having a characteristic morphology. Here, we describe a case with similar
      morphology characterised by eosinophilic cells, abundant intracytoplasmic lumina
      and scattered large ganglion-like tumour cells. There was focal staining for ALK
      demonstrated by immunohistochemistry. However, rather than exhibiting a
      chromosomal translocation involving ALK, the use of FISH and a break-apart probe
      demonstrated that there was increased copy number of intact 2p23, the chromosomal
      region containing the ALK gene. Furthermore, the use of comparative genomic
      hybridisation showed increase of the whole of chromosome 2 along with chromosomes
      6 and 17. There was no evidence of loss of 3p nor of trisomy of 7 associated with
      clear cell and papillary carcinoma, respectively. We suggest that this
      demonstrates a novel mechanism of upregulation of ALK activity by increased copy
      number occurring during the development of a renal carcinoma with the
      characteristic ALK-associated morphology. 

PMID- 24318420
TI  - Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly
      associated with epileptic seizures.
AB  - Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative
      disorder, is the result of a non-coding, pentanucleotide repeat expansion within
      intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar
      ataxia; yet, some families also have a high incidence of epilepsy. SCA10
      expansions containing penta- and heptanucleotide interruption motifs, termed
      "ATCCT interruptions," experience large contractions during germline
      transmission, particularly in paternal lineages. At the same time, these alleles
      confer an earlier age at onset which contradicts traditional rules of genetic
      anticipation in repeat expansions. Previously, ATCCT interruptions have been
      associated with a higher prevalence of epileptic seizures in one Mexican-American
      SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT
      interruptions confer a greater risk for developing seizures in these families.
      Notably, we find that the presence of repeat interruptions within the SCA10
      expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing
      epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7
      fold increase in having a positive family history of epilepsy (10.5-fold when
      considering patients of Mexican ancestry only). We conclude that the presence of
      repeat interruptions in SCA10 repeat expansion indicates a significant risk for
      the epilepsy phenotype and should be considered during genetic counseling. 

PMID- 24318421
TI  - The role of tissue factor pathway inhibitor-2 in malignant transformation of
      sinonasal inverted papilloma.
AB  - The aim was to evaluate the potential role of tissue factor pathway inhibitor-2
      (TFPI-2) in the process of malignant transformation of sinonasal inverted
      papilloma (SIP). We evaluated the expression of TFPI-2 in 23 SIP and 8 SIP with
      squamous cell carcinoma (IPcSCC), compared to 9 normal sinonasal mucosa by means
      of Western blot and immunohistochemistry staining. In addition, angiogenesis,
      vascular endothelial growth factor (VEGF) expression and microvessel density
      marked by CD105 staining were assessed. Correlation of TFPI-2 expression and
      angiogenesis in the process of malignant transformation of SIP was investigated.
      Western blot results demonstrated that the protein level of TFPI-2 in IPcSCC was
      significantly lower than that in the control group (P < 0.01). In addition,
      significant difference in TFPI-2 protein expression between SIP and IPcSCC was
      detected (P < 0.01). Higher number of microvessel per unit area (MVNA) was
      observed in IPcSCC compared to SIP (P < 0.01). Correlational analysis indicated
      positive correlation of VEGF and MVNA (r = 0.735), inverse correlation of TFPI-2
      and MVNA (r = -0.318). However, no significant correlation between TFPI-2 and
      VEGF was detected. We conclude that TFPI-2 might be a regulatory molecule in the
      malignant potential of SIP. Down regulation of TFPI-2 is associated with
      increased MVNA in IPcSCC, which may be involved in the process of malignant
      transformation of SIP.

PMID- 24318422
TI  - Chronic cerebrospinal venous insufficiency in patients with Meniere's disease.
AB  - To analyze the presence of chronic cerebrospinal venous insufficiency parameter
      and vascular abnormalities, in the internal jugular veins (IJVs) and/or vertebral
      veins in sitting and supine posture, in patients with Meniere's disease compared
      to healthy general population. A prospective study on 32 patients affected by
      definite Meniere was performed from February 2012 to January 2013. All subjects
      underwent an echo-color Doppler examination of the cerebrospinal venous flow. 21
      of the 32 Menieric patients showed a statistically significant reflux in the
      intracranial veins versus healthy (65.6 vs 25%; P < 0.001). A high prevalence of
      IJVs stenosis with hemodynamic changes (increased velocity or absence of flow)
      was observed (66.7 vs 33.3%; P < 0.05). The other parameters considered did not
      show statistically significant differences among the two groups. The results
      obtained showed a vascular pattern of cerebrospinal venous system present in
      patients affected by definite Meniere. This vascular impairment significantly
      affects the vascular areas more directly involved in the venous drainage of the
      inner ear. Thus venous stasis may be considered a further pathogenetic mechanism
      for development of Meniere's disease.

PMID- 24318423
TI  - Improving maternal and child health across the life course: where do we go from
      here?

PMID- 24318424
TI  - Dietary advice for reducing cardiovascular risk.
AB  - BACKGROUND: Changes in population diet are likely to reduce cardiovascular
      disease and cancer, but the effect of dietary advice is uncertain. This review is
      an update of a previous review published in 2007. OBJECTIVES: To assess the
      effects of providing dietary advice to achieve sustained dietary changes or
      improved cardiovascular risk profile among healthy adults. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials, the Database of
      Abstracts of Reviews of Effects (DARE) and the HTA database on The Cochrane
      Library (Issue 4, 2010). We searched MEDLINE (Ovid) (1950 to week 2 October 2010)
      and EMBASE (Ovid) (1980 to Week 42 2010). Additional searches were done on CAB
      Health (1972 to December 1999), CVRCT registry (2000), CCT (2000) and SIGLE (1980
      to 2000). Dissertation abstracts and reference lists of articles were checked and
      researchers were contacted. SELECTION CRITERIA: Randomised studies with no more
      than 20% loss to follow-up, lasting at least three months and involving healthy
      adults comparing dietary advice with no advice or minimal advice. Trials
      involving children, trials to reduce weight or those involving supplementation
      were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial quality and extracted data. Study authors were contacted for
      additional information. MAIN RESULTS: Forty-four trials with 52 intervention arms
      (comparisons) comparing dietary advice with no advice were included in the
      review; 18,175 participants or clusters were randomised. Twenty-nine of the 44
      included trials were conducted in the USA. Dietary advice reduced total serum
      cholesterol by 0.15 mmol/L (95% CI 0.06 to 0.23) and LDL cholesterol by 0.16
      mmol/L (95% CI 0.08 to 0.24) after 3 to 24 months. Mean HDL cholesterol levels
      and triglyceride levels were unchanged. Dietary advice reduced blood pressure by
      2.61 mm Hg systolic (95% CI 1.31 to 3.91) and 1.45 mm Hg diastolic (95% CI 0.68
      to 2.22) and 24-hour urinary sodium excretion by 40.9 mmol (95% CI 25.3 to 56.5)
      after 3 to 36 months but there was heterogeneity between trials for the latter
      outcome. Three trials reported plasma antioxidants, where small increases were
      seen in lutein and beta-cryptoxanthin, but there was heterogeneity in the trial
      effects. Self-reported dietary intake may be subject to reporting bias, and there
      was significant heterogeneity in all the following analyses. Compared to no
      advice, dietary advice increased fruit and vegetable intake by 1.18 servings/day
      (95% CI 0.65 to 1.71). Dietary fibre intake increased with advice by 6.5 g/day
      (95% CI 2.2 to 10.82), while total dietary fat as a percentage of total energy
      intake fell by 4.48% (95% CI 2.47 to 6.48) with dietary advice, and saturated fat
      intake fell by 2.39% (95% CI 1.4 to 3.37).Two trials analysed incident
      cardiovascular disease (CVD) events (TOHP I/II). Follow-up was 77% complete at 10
      to 15 years after the end of the intervention period and estimates of event rates
      lacked precision but suggested that sodium restriction advice probably led to a
      reduction in cardiovascular events (combined fatal plus non-fatal events) plus
      revascularisation (TOHP I hazards ratio (HR) 0.59, 95% CI 0.33 to 1.08; TOHP II
      HR 0.81, 95% CI 0.59 to 1.12). AUTHORS' CONCLUSIONS: Dietary advice appears to be
      effective in bringing about modest beneficial changes in diet and cardiovascular
      risk factors over approximately 12 months, but longer-term effects are not known.

PMID- 24318425
TI  - Structure-activity relationships between stimulus molecule and response of a
      pheromone receptor cell in turnip moth,Agrotis segetum : Modifications of the
      acetate group.
AB  - The response of an antennal receptor cell of the turnip moth,Agrotis segetum, was
      recorded during stimulation with a series of (Z)-7-dodecenyl acetate analogs with
      structural variations of the acetate group. The investigated receptor cell is
      known to be highly selective to (Z)-7-dodecenyl acetate. All parts of the acetate
      group were found to be of great importance for full biological activity. The
      results indicate very strict requirements on the shape of the polar functional
      group, as well as on its electron distribution for a successful interaction with
      the antennal receptor cell. 

PMID- 24318426
TI  - Convenient method applicable to single insects for collection and measurement of
      blend ratios of airborne pheromones from artificial sources.
AB  - A simple, fast, and sensitive technique has been developed for collecting
      airborne pheromones with potential application to a live and free-moving single
      insect. The surface within a disposable glass (Pasteur) pipet is sufficient to
      trap low nanogram quantities of sex pheromones, and molecules sensitive to
      oxidation such as (Z)-9-tetradecenal and (Z,E)-9,12-tetradecadienyl acetate are
      not significantly degraded during the chosen periods of aerial trapping. Rapid
      measurements of blend ratios for synthetic pheromone mixtures and detection at
      the low picogram level have been achieved by GC-MS. 

PMID- 24318427
TI  - Selective predation on chemically defended chrysomelid larvae : A Conditioning
      Process.
AB  - Laboratory experiments showed that femaleTenthredo olivacea prefer to prey upon
      insects of a previously encountered species, instead of upon unknown ones. This
      has been observed when comparing two natural prey of the sawfly, the larvae
      ofPhratora vitellinae and those ofPlagiodera versicolora. The two species secrete
      copious amounts of defensive secretion, the first salicylaldehyde, and the latter
      a mixture of cyclopentanic monoterpenes. The predator appears less reluctant when
      encountering a species whose secretion has been previously experienced. A
      selective pressure might thus exist favoring rare secretions, which is consistant
      with the well-known diversity of defensive compounds among sympatric insects. 

PMID- 24318428
TI  - Sex attractant for three species of the genusOncocnemis: O. chandleri (Grt.),O.
      cibalis (Grt.), andO. mackiei (B. & Benj.) (Lepidoptera: Noctuidae).
AB  - Oncocnemis chandleri, O. cibalis, andO. mackiei were attracted to chemically
      baited traps in the field. In all three cases, (5E,7Z)-dodecadienyl acetate was a
      key component for attraction. Attraction ofO. chandleri to traps baited with the
      (5E,7Z)-dodecadienyl acetate was inhibited by addition of (Z)-7-dodecenyl
      acetate.O. cibalis required both (5E,7Z)-dodecadienyl acetate and (Z)-7-dodecenyl
      acetate for attraction. Electroantennogram responses for the three species are
      also reported. 

PMID- 24318429
TI  - Alert odor from skin gland in deer.
AB  - Black-tailed deer (Odocoileus hemionus columbianus) discharge an odor from the
      metatarsal (MT) gland, located on the hindleg, when disturbed or alarmed. Freely
      moving, captive deer were exposed to the MT odor by means of a remote-release
      apparatus. Responses by males and females to MT odor from both sexes were
      recorded with a coding system and a video camera. When the odor was present,
      females became more alert and left the site more often than in the presence of
      control odors, odorless air, or deer urine. It is concluded that the MT secretion
      provides an alert signal, placing the odor into the class of alarm pheromones.
      There is no evidence that the closely related white-tailed deer,O. virginianus,
      possesses this alert (or alarm) odor system to the same degree. 

PMID- 24318430
TI  - Identification and source of a queen-specific chemical in the pharaoh's
      ant,Monomorium pharaonis (L.).
AB  - Fertile queens of the antMonomorium pharaonis produce a chemical substance which
      is not present in worker ants or in young, alate (virgin) queens. The material
      has been identified as (E,E,E)-1-isopropenyl-4,8,12-trimethylcyclotetradeca
      3,7,11-triene (neocembrene). This chemical is produced in the Dufour's gland of
      fertile queens and may serve as a queen-recognition pheromone. 

PMID- 24318431
TI  - Characterization of and male adaptation to pheromone of femaleTrichostrongylus
      colubriformis (Nematoda).
AB  - Males of the ruminant nematodeTrichostrongylus colubriformis were significantly
      attracted to an incubate from their females during in vitro assay. Exposure of
      males to sera from uninfected and infected animals or selected neurotransmitters
      had no effect on their subsequent responsiveness to the female's pheromone. In
      contrast, exposure to 1500 female-hours of pheromone decreased male
      responsiveness after moderate rinsing prior to bioassay. Rinsing of the males
      with larger volumes of Tyrode's solution prior to in vitro assay increased their
      subsequent response to the female's pheromone. High-performance liquid
      chromatography yielded a presumptive pheromone peak with a fivefold increase in
      biological activity. This peak was soluble in alcohols and tetrahydrofuran, based
      on elution from reverse-phase Sep-Pak cartridges. Stability of the peak was
      increased by EDTA or ascorbic acid (10 mM). Storage for six weeks in ascorbic
      acid at 4  degrees C allowed recovery of 47.3% of the original material. 

PMID- 24318432
TI  - Olfaction in the boll weevil,Anthonomus grandis Boh. (Coleoptera: Curculionidae):
      Electroantennogram studies.
AB  - Electroantennogram (EAG) techniques were utilized to measure the antennal
      olfactory responsiveness of adult boll weevils,Anthonomus grandis Boh.
      (Coleoptera: Curculionidae), to 38 odorants, including both insect and host plant
      (Gossypium hirsutum L.) volatiles. EAGs of both sexes were indicative of at least
      two receptor populations: one receptor population primarily responsive to
      pheromone components and related compounds, the other receptor population
      primarily responsive to plant odors. Similar responses to male aggregation
      pheromone components (i.e., compounds I, II, and III + IV) were obtained from
      both sexes, but females were slightly more sensitive to I. Both sexes were highly
      responsive to components of the "green leaf volatile complex," especially the six
      carbon saturated and monounsaturated primary alcohols. Heptanal was the most
      active aldehyde tested. More acceptors responded to oxygenated monoterpenes than
      to monoterpene hydrocarbons. beta-Bisabolol, the major volatile of cotton, was
      the most active sesquiterpene. In general, males, which are responsible for host
      selection and pheromone production, were more sensitive to plant odors than were
      females. In fact, males were as sensitive to beta-bisabolol and heptanal as to
      aggregation pheromone components. Electrophysiological data are discussed with
      regard to the role of insect and host plant volatiles in host selection and
      aggregation behavior of the boll weevil. 

PMID- 24318433
TI  - Role of glandular scales of lepidote rhododendrons in insect resistance.
AB  - Glandular scales on selected lepidote rhododendron species varied in density from
      109 +/- 13 to 4180 +/- 60/cm(2) of leaf surface. Globules contained within the
      scales stained with Sudan IV, a lipophilic dye. Essential oil contents of the
      scales varied with species from 24 +/- 8 to 151 +/- 35 ng/scale. Black vine
      weevil [(Otiorhynchus sulcatus (F.)] feeding on leaves from a sample of
      rhododendron species was inversely related to leaf essential oil content, and
      weevil feeding on membrane filters was inhibited by application of essential oil
      extracts from leaves of most lepidote rhododendrons tested. Results suggest that
      the glandular scales of the lepidote rhododendrons function, at least in part, in
      plant defense against insects. 

PMID- 24318434
TI  - Identification of ant repellent allomone produced by social waspPolistes fuscatus
      (Hymenoptera: Vespidae).
AB  - Two active components were isolated from the ant repellent secretion produced by
      glandular cells on the sixth (terminal) gastral sternite ofPolistes fuscatus (F.)
      females. One of the components was identified as methyl palmitate. Field
      bioassays with synthetic methyl palmitate showed it had repellent activity
      againstSolenopsis geminata (F.)Forelius pruinosus (Roger), andPheidole sp. The
      effectiveness of the repellent was greater againstF. pruinosus andPheidole sp.
      than againstS. geminata. Four methyl ester homologs of methyl palmitate also were
      field tested for repellent activity: methyl myristate had repellent activity
      against all three ant species, whereas methyl stearate, methyl linoleate, and
      methyl linolenate exhibited no repellency. 

PMID- 24318435
TI  - Influence of mustelid scent-gland compounds on suppression of feeding by snowshoe
      hares (Lepus americanus).
AB  - This study investigated the influence of mustelid anal-gland compounds in
      suppressing feeding by snowshoe hares on coniferous tree seedlings. Pen and field
      bioassays indicated that 3-propyl-1,2-dithiolane from the stoat (Mustela
      erminea), and secondarily, 2,2-dimethylthietane from the mink (M. vison) had a
      very negative effect on feeding behavior of hares. The major component of stoat
      anal gland secretions, 2-propylthietane, and the related compounds, thietane and
      2-methylthietane, were not effective. 3,3-Dimethyl-1,2-dithiolane from the least
      weasel (M. nivalis) and ferret (M. putorius) and di-n-propyldisulfide (acyclic
      analog of 3-propyl-1,2-dithiolane) similarly did not affect hare feeding. 3
      Propyl-1,2-dithiolane and 2,2-dimethylthietane (also found inM. erminea) may act
      as interspecific chemical signals which induce a fear or avoidance response in
      hares. Such compounds have outstanding potential as area repellents to reduce
      crop and livestock depredations. Our study reports one of the first practical
      utilizations of mammalian semiochemicals in crop protection and wildlife
      management. 

PMID- 24318437
TI  - On being there.

PMID- 24318438
TI  - The parish clergy as a mental health resource.
AB  - This paper presents observations on the assets and liabilities of the parish
      clergy as a mental health resource within the community. These observations are
      drawn from a ten-year program of continuing education for cleargy in mental
      health, which focuses on daily pastoral experience. The parish setting is similar
      in many respects to the service area of a community mental health center. The
      clergy's assets often include availability, experience, tradition, and the
      special significance of the religious leader. Inadequate training in mental
      health skills and the complex demands of parish life are among the problems
      confronting the clergy in this area. On the whole, the pastoral role offers a
      unique and highly useful opportunity for positive psychological intervention. 

PMID- 24318436
TI  - Plant-determined variation in cardenolide content and thin-layer chromatography
      profiles of monarch butterflies,Danaus plexippus reared on milkweed plants in
      California : 3. Asclepias californica.
AB  - Variation in gross cardenolide concentration of the mature leaves of 85Asclepias
      californica plants collected in four different areas of California is a
      positively skewed distribution ranging from 9 to 199 MUg of cardenolide per 0.1 g
      dry weight with a mean of 66 MUg/0.1 g. Butterflies reared individually on these
      plants in their native habitats contained a normal distribution of cardenolide
      ranging from 59 to 410 MUg of cardenolide per 0.1 g dry weight with a mean of 234
      MUg. Cardenolide uptake by the butterflies was a logarithmic function of plant
      concentration. Total cardenolide per butterfly ranged from 143 to 823 MUg with a
      mean of 441 MUg and also was normally distributed. Populational variation of
      plant cardenolide concentrations occurs within subspecies, but the northern
      subspeciesA. c. greenei does not differ significantly from the southernA. c.
      californica. Generally higher concentrations occur in butterflies from northern
      populations and in females. No evidence was adduced that cardenolides in the
      plants adversely affected the butterflies. Low cardenolide concentrations in the
      leaves and the absence of cardenolides in the latex characterize bothA.
      californica andA. speciosa, but notA. eriocarpa. Thin-layer chromatography in two
      solvent systems isolated 24 cardenolide spots in the plants, of which 18 are
      stored by the butterflies. There was a minor difference in the cardenolide spot
      patterns due to geographic origin of the plants, but as in our previous studies,
      none in the sexes of the butterflies. UnlikeA. eriocarpa andA. speciosa, A.
      californica plants lack cardenolides withRf values greater than digitoxigenin.
      Overall, the cardenolides of bothA. californica andA. speciosa are more polar
      than those inA. eriocarpa. A. californica plants contain cardenolides of the
      calotropagenin series including calotropin, calactin, and uscharidin, and the
      latter is metabolically transformed by monarch larvae to calactin and calotropin.
      Cardenolides of this series also occur inA. vestita, andA. cordifolia from
      California, the neotropicalA. curassavica, and the AfricanCalotropis procera,
      Gomphocarpus spp., andPergularia extenso; they therefore cross established
      taxonomic lines.A. californica is the predominant early season milkweed in
      California and may be important in providing chemical protection to the spring
      generation of monarchs in the western United States.A. speciosa, A. eriocarpa,
      andA. californica each imparts distinctive cardenolide fingerprints to the
      butterflies, so that ecological predictions are amenable to testing. 

PMID- 24318439
TI  - Maintaining religious values in a nonreligious counseling program.
AB  - Both Christianity and HE therapy may be viewed as dealing with searching
      questions for those of us who dare to pursue the quest. A sense of mission is to
      be found in both humanistic existentialism and Christianity when we query: Who am
      I? What is my relationship to the world and those in it? What do I truly believe
      and how do I want to act upon my beliefs?Thus, both Christianity and HE therapy
      explore searching questions for those who dare to pursue the answers, to reveal
      their individuality, their fears, their aloneness, and to explore the
      possibilities of existence.Finally, it is suggested that both Christianity and HE
      therapy are capable of creating an honest atmosphere that makes it easier for us
      to remove our masks, to reveal and share our doubts, resentments, and anxieties,
      and to do so in an atmosphere of acceptance that brings healing and wholeness,
      whether as a Christian or as a nonreligious humanistic existentialist. Rather
      than polarization or a dichotomy existing between the two positions, similarities
      have been found to be inherent, and integration and reconciliation are possible
      and feasible, allowing students to maintain their religious beliefs with
      integrity while at the same time incorporating university teachings. 

PMID- 24318440
TI  - Behavior modification, brainwashing, religion, and the law.

PMID- 24318441
TI  - Public rituals versus private treatment: Psychodynamics of prayer.

PMID- 24318442
TI  - Medicine and morals and mao.

PMID- 24318443
TI  - Sin as neurosis-Neurosis as sin: Further implications of a halachic
      metapsychology.

PMID- 24318444
TI  - Two ideas due for the ragbag.

PMID- 24318445
TI  - Caring for parents who have lost an infant.

PMID- 24318446
TI  - Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and
      growth.
AB  - Cancer cells rely on aerobic glycolysis to maintain cell growth and proliferation
      via the Warburg effect. Phosphoglycerate dehydrogenase (PHDGH) catalyzes the
      first step of the serine biosynthetic pathway downstream of glycolysis, which is
      a metabolic gatekeeper both for macromolecular biosynthesis and serine-dependent
      DNA synthesis. Here, we report that PHDGH is overexpressed in many ER-negative
      human breast cancer cell lines. PHGDH knockdown in these cells leads to a
      reduction of serine synthesis and impairment of cancer cell proliferation.
      However, PHGDH knockdown does not affect tumor maintenance and growth in
      established breast cancer xenograft models, suggesting that PHGDH-dependent
      cancer cell growth may be context-dependent. Our findings suggest that other
      mechanisms or pathways may bypass exclusive dependence on PHGDH in established
      human breast cancer xenografts, indicating that PHGDH is dispensable for the
      growth and maintenance and of tumors in vivo. 

PMID- 24318447
TI  - Diagnosis and treatment of vascular malformations of the brain.
AB  - OPINION STATEMENT: Vascular malformations of the brain are often found in the
      workup of intracranial hemorrhage, seizures, focal neurological deficits, or
      headaches. Although CT-angiography may reveal an underlying arteriovenous
      malformation (AVM) or arteriovenous fistula (AVF), other vascular malformations
      are not easily evaluated on CT and are better seen on magnetic resonance imaging.
      For the evaluation of AVMs and AVFs, formal digital subtraction angiography
      remains the gold standard. In the case of AVMs, AVFs, or cavernous malformations
      (CMs), the lesion may serve as the etiologic source of the symptoms and thus
      warrant treatment. When feasible, microsurgical resection is the optimal
      treatment option for AVMs and CMs. Endovascular embolization may serve as a
      crucial adjunct to microsurgery in the treatment of AVMs. Depending on their
      vascular anatomy, AVFs may be treated by either endovascular embolization or
      microsurgery. For inoperable AVMs and dural AVFs necessitating treatment,
      stereotactic radiosurgery (SRS) may serve as a viable treatment alternative.
      Capillary telangiectasias and developmental venous anomalies (DVAs) are often
      incidental findings; they may be found in association with CMs but are not
      generally considered targets for treatment. Herein, we review diagnostic methods,
      natural history, and treatment options for these cerebral vascular malformations.

PMID- 24318448
TI  - Molecular cloning of pea mRNAs encoding a shoot-specific polypeptide and light
      induced polypeptides.
AB  - The molecular cloning of cDNA corresponds to pea seedling mRNA sequences encoding
      a shoot-specific polypeptide, the small subunit of the ribulose 1,5 biphosphate
      carboxylase and a component of the light-harvesting chlorophyll a/b complex is
      described. cDNA prepared from polysomal poly(A)RNA of light-grown shoots was
      enriched for shoot-specific and light-induced sequences by heterologous liquid
      hybridization with mercurated polysomal poly(A)RNA of dark-grown roots, followed
      by sulfhydryl chromatography. Cloned shoot-specific sequences were identified by
      2D electrophoretic analysis of hybrid release translation products. The cloned
      shoot-specific sequence corresponded to a mRNA of 850 nt present both in light
      and dark-grown shoots, and produced anin vitro translation product of Mr27 500
      and isoelectric point of 4.7. 

PMID- 24318449
TI  - Mitochondrial plasmid-like molecules in fertile and male sterileVicia faba L.
AB  - Biochemical analysis and electron microscopy showed that mitochondria of both the
      fertile and the male sterile 350 and 447 cytoplasms ofVicia faba. L. contain two
      small supercoiled DNA molecules of mean length of 1 700 and 1 420 base pairs in
      addition to the main mitochondrial DNA of high molecular weight. By agarose gel
      electrophoresis, the male sterile cytoplasm 350 is distinguished from the fertile
      cytoplasm and from the male sterile cytoplasm 447 by the presence of an
      additional supercoiled DNA molecule of approximately 1 540 bp. 

PMID- 24318450
TI  - Two higher molecular weight forms related to ferritin are synthesizedin vitro by
      RNA from developing cotyledons and leaves ofPhaseolus vulgaris.
AB  - Using RNA from developing cotyledons and leaves of bean two products were
      synthesizedin vitro, with Mr 31000 and 31500 which are antigenically related to
      the subunit of phytoferritin (Mr 26500). The relative abundance of the two
      products is dependent on the type of tissue from which the RNA was derived.
      Evidence is presented for the assumption that both products are precursors of the
      phytoferritin subunit. The hypothesis is put forward that different transit
      sequences direct the phytoferritin subunits to different cell organelles. 

PMID- 24318451
TI  - Pathogenesis-related proteins in plants and tissues ofNicotiana tabacum
      transformed byAgrobacterium tumefaciens.
AB  - Large amounts of pathogenesis-related (PR) proteins were found inNicotiana
      tabacum crown gall tissue, following transformation of normal tobacco cells
      withAgrobacterium tumefaciens. In contrast, PR proteins were not detected in
      leaves of grafted plants that had been recovered from crown gall tissue even
      though these plants were still transformed as shown by their inability to form
      roots and ability to produce octopine. No difference was observed in
      susceptibility to virus infection between untransformed and transformed plants
      grafted onto identical rootstocks. The results are discussed in relation to
      physiological factors controlling PR protein induction and virus resistance. 

PMID- 24318452
TI  - Clonal analysis of heterogeneous crown gall tumor tissues induced by wild-type
      and shooter mutant strains ofAgrobacterium tumefaciens-expression of T-DNA genes.
AB  - Tumors were induced by anAgrobacterium tumefaciens strain with a wild-type
      octopine Ti plasmid and by shooter mutants with a transposon insertion in the
      auxin-locus of the T-region. Cloning of isolated axenic tumor tissues revealed
      that in all cases they consisted of tumor cells (10-26%) next to a majority of
      normal cells. The tumor clones that had been induced by the strain with the wild
      type Ti plasmid all grew as amorphous calli. Tumor, clones induced by a shooter
      mutant were of two different types. One type of clone grew well on phytohormone
      free medium. this type invariably regenerated tumorous shoots abundantly on this
      medium. The other type of clone only grew after the addition of auxin and
      cytokinin to the culture medium, but slow growth also took place in the presence
      of only auxin. This type never regenerated shoots spontaneously. After
      stimulation by a high level of kinetin, however, a few shoots were also obtained
      from these clones. One of these shoots, like other tumorous shoots, contained the
      tumor-specific enzyme octopinesynthase (Ocs), but in contrast to other tumorous
      shoots formed a root-system.The expression of T-DNA genes in shoots proliferating
      from the cloned tumor tissues induced by a mutant with an insertion in the region
      for transcript tr. 2 was studied by northern blot hybridization. Except for tr.2
      the T-DNA transcripts were detected in the tumorous shoots analysed, including
      the transcript, tr.1 from the auxin-locus and tr.4 from the cytokinin-locus. This
      shows that the presence of these transcripts, which are assumed to be responsible
      for the tumorigenic character of tumor cells, does not interfere with the
      differentiation of shoot cells.One of the shooty tumor clones (TSO38) showed an
      unstable character with regard to octopine synthase activity (Ocs+/-). For, TSO38
      and some of its subclones, it was found that only 4% of the regenerated shoots
      were Ocs(+). Northern blot hybridization revealed that the mRNA for octopine
      synthase was present in extremely low quantity in the population of TSO38 derived
      shoots.The finding that it was possible to force shoots from clone TSO38 and from
      subclone TSO38-23(-) that were Ocs(-) to become Ocs(+), proved that the gene for
      octopine synthase was present in the Ocs(-) shoots and that this gene showed
      unstable expression due to regulation at the level of transcription. 

PMID- 24318453
TI  - Nucleotide sequence of the T-DNA region from theA grobacterium tumefaciens
      octopine Ti plasmid pTi15955.
AB  - The complete nucleotide sequence of the transferred region (T-DNA) of an octopine
      tumor inducing (Ti) plasmid fromAgrobacterium tumefaciens (pTi15955) has been
      determined. A total of 24 595 nucleotides extending approximately 900 bases to
      either side of the outermost, T-DNA boundaries was sequenced. Computer analysis
      of the sequenced portion of the Ti plasmid revealed that recognition sites for 72
      restriction endonucleases are present in the DNA sequence at least once; no site
      forEcoK exists in this DNA sequence. Two imperfect 24 base repeats border the T
      DNA sequence; the left starts at position 909 and the right ends at position 23
      782, giving the T-DNA region a total length, of 22 874 nucleotides. Another two
      similar 24 base repeats lie within T-DNA and divide it, into three distinct
      domains: T-left (TL-DNA) 13 175 bp of apparently eukaryotic origin; T-center (TC
      DNA) 1816 bp of prokaryotic origin; and T-right (TR-DNA) 7 883 bp of eukaryotic
      origin. The T-DNA contains nine reported transcripts, however, 26 open reading
      frames longer than 300 bases that start with an ATG initiation codon were found.
      Fourteen open reading frames are bounded by putative eukaryotic promoters,
      ribosome binding sites, and poly(A) addition sites and occur only in TL-and TR
      DNAs. No open reading frames showing eukaryotic promoter sequences are located
      within the TC-DNA. 

PMID- 24318455
TI  - Molecular characterization and phylogenetic analysis of three odorant binding
      protein gene transcripts in Dendrolimus species (Lepidoptera: Lasiocampidae).
AB  - Pine caterpillar moths, Dendrolimus spp. (Lepidoptera: Lasiocampidae), are
      serious economic pest of pines. Previously, phylogenetic analyses of Dendrolimus
      using different methods yielded inconsistent results. The chemosensory systems of
      insects may play fundamental roles in promoting speciation. Odorant-binding
      proteins (OBPs) participate in the first step of odor detection. Studying the
      evolution of OBPs in closely related species may help us to identify their role
      in speciation. We identified three OBPs - one pheromone-binding protein and two
      general odorant-binding proteins - from male antennae of four Dendrolimus
      species, D. superans (Butler), D. punctatus (Walker), D. kikuchii Matsumura, and
      D. houi Lajonquiere, the olfactory recognition systems of which had not been
      previously investigated. We analyzed their molecular characteristics and compared
      their sequences to those of OBPs in D. tabulaeformis Tsai et Liu. Ka/Ks ratio
      analyses among the five Dendrolimus species indicate that PBP1 genes experienced
      more evolutionary pressure than the GOBPs. Phylogenetic relationships of PBP1 and
      GOBP1 both indicated that D. houi was the basal species, then branched D.
      kikuchii, while D. tabulaeformis, D. punctatus, and D. superans evolved more
      recently. These relationships are consistent with the changes in sex pheromone
      components of these five species. Dendrolimus tabulaeformis and D. punctatus are
      closely related sister species. However, the distances among GOBP2 sequences in
      the five Dendrolimus were very short, and the relationships of D. houi and D.
      kikuchii could not be resolved. Integrating our results with those of previous
      studies, we hypothesized that D. kikuchii, D. punctatus and D. superans evolved
      from the basal ancestor because of sex pheromone mutations and environmental
      pressure.

PMID- 24318456
TI  - Studies on genetic diversity of bovine viral diarrhea viruses in Danish cattle
      herds.
AB  - Scandinavian countries have successfully pursued bovine viral diarrhea virus
      (BVDV) eradication without the use of vaccines. In Denmark, control and
      eradication of BVDV were achieved during the last two decades, but occasionally
      new BVDV infections are detected in some Danish cattle herds. The aim of this
      study was to determine recent BVDV subtypes isolated from 4 Danish herds (A, B,
      C, and D) isolated in 2009-2012 and to analyze the genetic variation of these
      isolates within the same herd and its relation with those of other herds. The
      results showed that three herds (B, C, D) were BVDV 1-b and only one herd (herd
      A) was BVDV 1-d, no other subtypes were detected. The deduced E2 amino acids
      result showed a high identity percent (99-100 %) between isolates originating
      from the same herd, but with higher variation compared to isolates of the other
      herds. Some of these new Danish strains have closer relationship to BVDVs from
      outside Denmark than to older Danish strains indicating that these are new
      introductions to Denmark. In conclusion, BVDV-1 subtypes recently detected in
      Denmark were only subtypes 1b and 1d, and BVDV infections established in a herd
      is genetically stable over a long time period.

PMID- 24318457
TI  - Intraluminal exfoliated cancer cells and effectiveness of bowel ligatures during
      sigmoidectomy for sigmoid colon cancer.
AB  - PURPOSES: To establish the efficiency of bowel ligatures in colon cancer surgery,
      focusing on the extent to which exfoliated cancer cells are shed in the colonic
      lumen during sigmoidectomy. METHODS: Twenty consecutive patients who underwent
      sigmoidectomy for sigmoid colon cancer were prospectively randomized into two
      groups: the "ligatures group", in which bowel ligatures were placed, 3, 5, 10 cm
      from the tumor proximally and distally before dissection; and the "no ligatures
      group", in which the corresponding sites were ligated only immediately before
      taking the specimen out. Each colonic segment ligated was irrigated with saline
      and samples were sent for blind cytological examination. RESULTS: Cancer cells
      were found in the colonic segment where the tumor was located, in 18 of 20
      samples. The frequency of free cancer cells decreased from 50 to 0 % (p < 0.04)
      in the distal 3-5 cm colonic segment and from 80 to 20 % (p < 0.03) in the
      proximal colonic segment after performing bowel ligatures. Free cancer cells were
      confirmed in 1 of 10 samples at both colonic segments 5-10 cm from the tumor,
      even after bowel ligatures. CONCLUSIONS: Intraluminal exfoliated cancer cells
      could be eliminated by placing bowel ligatures during sigmoidectomy. Measures
      should be considered to eliminate exfoliated cancer cells during colectomy, even
      after placing bowel ligatures.

PMID- 24318458
TI  - A supramolecular photosynthetic model made of a multiporphyrinic array
      constructed around a C60 core and a C60-imidazole derivative.
AB  - The photophysical properties of a supramolecular fullerene-porphyrin ensemble
      resulting from the self-assembly of a pyrrolidinofullerene-imidazole derivative
      (F1) with a multimetalloporphyrin array constructed around a hexasubstituted
      fullerene core (F(ZnP)12) have been investigated. The fullerene hexa-adduct core
      of the host system does not play any active role in the cascade of photoinduced
      events of the supramolecular ensemble, indeed no intercomponent photoinduced
      processes could be observed in host F(ZnP)12. In contrast, upon axial
      coordination with the monosubstituted fullerene guest F1, a quantitative
      quenching of the fluorescence signal of the metalloporphyrins was observed for
      the supramolecular complex [F(ZnP)12(F1)n] both in polar and nonpolar solvents.
      In toluene, the supramolecular ensemble exhibits a charge transfer emission
      centered around nm, suggesting the occurrence of intramolecular face-to-face
      interactions of F1 with neighboring metalloporphyrin moieties within the self
      assembled photoactive array. This mechanism is supported by the fact that a one
      order of magnitude increase in the binding constant was observed for the
      supramolecular complex [F(ZnP)12(F1)n] when compared with a reference system
      lacking the pyrrolidinofullerene unit. In benzonitrile, a long-lived charge
      separated state (tau=0.3 MUs) has been detected for the supramolecular adduct.

PMID- 24318459
TI  - Adaptive, maladaptive, mediational, and bidirectional processes of relational and
      physical aggression, relational and physical victimization, and peer liking.
AB  - A three-wave longitudinal study among ethnically diverse preadolescents (N = 597
      at Time 1, ages 9-11) was conducted to examine adaptive, maladaptive,
      mediational, and bidirectional processes of relational and physical aggression,
      victimization, and peer liking indexed by peer acceptance and friendships. A
      series of nested structural equation models tested the hypothesized links among
      these peer-domain factors. It was hypothesized that (1) relational aggression
      trails both adaptive and maladaptive processes, linking to more peer
      victimization and more peer liking, whereas physical aggression is maladaptive,
      resulting in more peer victimization and less peer liking; (2) physical and
      relational victimization is maladaptive, relating to more aggression and less
      peer liking; (3) peer liking may be the social context that promotes relational
      aggression (not physical aggression), whereas peer liking may protect against
      peer victimization, regardless of its type; and (4) peer liking mediates the link
      between forms of aggression and forms of peer victimization. Results showed that
      higher levels of peer liking predicted relative increases in relational
      aggression (not physical aggression), which in turn led to more peer liking. On
      the other hand, more peer liking was predictive of relative decreases in
      relational aggression and relational victimization in transition to the next
      grade (i.e., fifth grade). In addition, relational victimization predicted
      relative increases in relational aggression and relative decreases in peer
      liking. Similarly, physical aggression was consistently and concurrently
      associated more physical victimization and was marginally predictive of relative
      increases in physical victimization in transition to the next grade. More peer
      liking predicted relative decreases in physical victimization, which resulted in
      lower levels of peer liking. The directionality and magnitude of these paths did
      not differ between boys and girls.

PMID- 24318460
TI  - Serious shoulder injuries in professional soccer: return to participation after
      surgery.
AB  - PURPOSE: An evidence base for the management and prevention of shoulder injuries
      in soccer is lacking. The aim of this study was to demonstrate the type,
      mechanism and recovery time after surgery associated with serious shoulder
      injuries sustained in professional soccer to build an evidence base foundation.
      METHODS: Fifty-two professional soccer players underwent shoulder surgery for
      injuries sustained during match play. Of these, 25 fulfilled the inclusion
      criteria. Data were collected for injury mechanism and type; clinical,
      radiological and surgical findings and procedures; and return to full
      participation. Subjects were all managed by the same surgeon. RESULTS: Labral
      injuries represented the most common injury type affecting 21 (84 %) subjects;
      two rotator cuff (8 %) and two combined labral/rotator cuff (8 %) injuries were
      less common. Fourteen (56 %) subjects sustained a high-energy trauma injury in a
      combined abduction and external rotation position. Six (24 %) subjects sustained
      a low-energy trauma mechanism in variable positions, while five (20 %) had a
      gradual onset of symptoms. Twenty-two (88 %) subjects reported a dislocation as a
      feature of their presentation. All of the subjects with high- and low-energy
      trauma mechanisms reported a dislocation occurring at the time of injury. Eight
      (32 %) subjects had sustained a previous significant shoulder injury to the
      ipsilateral side. Goalkeepers did not sustain low-energy trauma injuries.
      Outfield players returned to full participation in a mean time of 11.6 weeks,
      while goalkeepers did so in 11.1 weeks post-surgery. Return to participation time
      ranged from 7 to 24 weeks with a median of 11 weeks. CONCLUSION: Professional
      soccer players can expect a return to participation within 12 weeks post-surgery.
      The majority of serious shoulder injuries in soccer occur at a positional extreme
      of external rotation and abduction in high-energy situations, while a significant
      number occur in low-energy situations away from this position. Most serious
      shoulder injuries in professional soccer are dislocations. Previous shoulder
      injury is considered a risk factor. LEVEL OF EVIDENCE: IV.

PMID- 24318461
TI  - Effects of silver nanoparticles (NM-300K) on Lumbricus rubellus earthworms and
      particle characterization in relevant test matrices including soil.
AB  - The impact of silver nanoparticles (AgNP; at 0 mg Ag/kg, 1.5 mg Ag/kg, 15.4 mg
      Ag/kg, and 154 mg Ag/kg soil) and silver nitrate (AgNO3 ; 15.4 mg Ag/kg soil) on
      earthworms, Lumbricus rubellus, was assessed. A 4-wk exposure to the highest AgNP
      treatment reduced growth and reproduction compared with the control. Silver
      nitrate (AgNO3 ) exposure also impaired reproduction, but not as much as the
      highest AgNP treatment. Long-term exposure to the highest AgNP treatment caused
      complete juvenile mortality. All AgNP treatments induced tissue pathology.
      Population modeling demonstrated reduced population growth rates for the AgNP and
      AgNO3 treatments, and no population growth at the highest AgNP treatment because
      of juvenile mortality. Analysis of AgNP treated soil samples revealed that single
      AgNP and AgNP clusters were present in the soil, and that the total Ag in soil
      porewater remained high throughout the long-term experiment. In addition, immune
      cells (coelomocytes) of earthworms showed sensitivity to both AgNP and AgNO3 in
      vitro. Overall, the present study indicates that AgNP exposure may affect
      earthworm populations and that the exposure may be prolonged because of the
      release of a dissolved Ag fraction to soil porewater.

PMID- 24318462
TI  - Kruppel-like factor 4 regulates blood-tumor barrier permeability via ZO-1,
      occludin and claudin-5.
AB  - Blood-tumor barrier (BTB) constitutes an efficient organization of tight
      junctions which significantly reduce permeability for chemotherapy drugs. Kruppel
      like factor 4 (KLF4), a member of the Kruppel-like family, has been documented in
      endothelial cells and may serve as an essential regulator of endothelial barrier
      function. However, our knowledge about the expression and function of KLF4 in the
      endothelial cells of BTB still remains unclear. In this study, we sought to
      investigate the role of KLF4 in regulation of BTB function as well as the
      potential molecular mechanisms. Quantitative RT-PCR, Western blot, and
      immunofluorescence assays demonstrated that KLF4 was down-regulated in the glioma
      endothelial cells (GECs) which were obtained through endothelial cells co
      cultured with glioma cells. Short hairpin RNA targeting KLF4 impaired the
      integrity of BTB detected by trans-endothelial electric resistance assay, and
      meanwhile reduced the expression of ZO-1, occludin and claudin-5, demonstrated by
      quantitative RT-PCR, Western blot, and immunofluorescence assays. Depletion of
      KLF4 increased BTB permeability to small molecules detected by permeability
      assays. Furthermore, luciferase assays and chromatin immunoprecipitation assays
      showed that KLF4 up-regulated the promoter activities and interacted with "CACCC"
      DNA sequence presented in the promoters of ZO-1, occludin, and claudin-5. GATA-1,
      GATA-6, Sp1, and Sp3 factors participated in KLF4 regulation of promoter
      activities through binding to the promoters of tight junctions related proteins.
      Collectively, our results indicated that KLF4 is a key transcriptional regulator
      of BTB function by regulating expressions of tight junction related proteins,
      which would draw growing attention to KLF4 as a potential target for glioma
      therapy.

PMID- 24318463
TI  - CT-guided injection of N-butyl cyanoacrylate glue for treatment of chylous leak
      after aorto-mesenteric bypass.
AB  - Lymphangiography and thoracic duct embolization are well-described techniques for
      the diagnosis and treatment of thoracic lymphatic leaks refractory to
      conservative treatment. However, thoracic duct embolization is not an option in
      patients with abdominal chylous leaks. The present report describes a 68-year-old
      man who underwent an aortomesenteric bypass complicated by a high-output
      postoperative chylothorax (>2,000 ml/day) and chylous ascites (>7,000
      ml/paracentesis). Ultrasound-guided intranodal lymphangiography demonstrated a
      retroperitoneal lymphatic leak tracking along the vascular graft into the
      peritoneal cavity. Computed tomography-guided lymphatic duct occlusion with N
      butyl cyanoacrylate glue was performed, resulting in successful treatment of both
      chylothorax and chylous ascites. 

PMID- 24318464
TI  - Removal of the antiscatter grid during routine biliary interventional procedures
      performed in a flat-panel interventional suite: preliminary data on image quality
      and patient radiation exposure.
AB  - PURPOSE: To determine whether grid removal during routine biliary interventional
      procedures performed in a flat-panel interventional suite results in adequate
      image quality and a significant decrease of patient radiation exposure. MATERIALS
      AND METHODS: Routine biliary interventional procedures were defined as those in
      which absence of fine image detail during fluoroscopy carries no procedural
      impact, including substitution of internal-external biliary drains (n = 25) or
      bilioplasty of benign biliary anastomotic strictures (n = 5). All patients had
      undergone a previous procedure in which the grid was used. Constant object-to
      detector and source-to-image distance were maintained in each patient during the
      grid/no-grid procedures. The same fluoroscopy protocol was used for all
      examinations. The dose area product (DAP [cGy.cm(2)]) and procedure fluoroscopy
      time (seconds) were recorded for each procedure. DAP was normalized per unit of
      fluoroscopy time (nDAP [cGy.cm(2)/s]). RESULTS: In all procedures, image quality
      was considered adequate by two different interventional radiologists, and all
      procedures were successfully completed without significant changes in fluoroscopy
      time between the two groups (p = 0.13). In every procedure without the grid, nDAP
      was inferior compared with nDAP in procedures performed using the grid. The mean
      decrease in dose was 39.2 +/- 23.5 % (p = 0.000001). CONCLUSION: Our preliminary
      data show that removal of the grid during routine biliary procedures is feasible
      and results in a significant decrease of patient radiation exposure. This seems
      of particular relevance because most of these patients require frequent
      reintervention. Larger studies with more procedures are warranted to confirm
      these data.

PMID- 24318465
TI  - B vitamins for pain following spinal cord trauma.

PMID- 24318466
TI  - Adding Postal Follow-Up to a Web-Based Survey of Primary Care and
      Gastroenterology Clinic Physician Chiefs Improved Response Rates but not Response
      Quality or Representativeness.
AB  - This study assessed whether postal follow-up to a web-based physician survey
      improves response rates, response quality, and representativeness. We recruited
      primary care and gastroenterology chiefs at 125 Veterans Affairs medical
      facilities to complete a 10-min web-based survey on colorectal cancer screening
      and diagnostic practices in 2010. We compared response rates, response errors,
      and representativeness in the primary care and gastroenterology samples before
      and after adding postal follow-up. Adding postal follow-up increased response
      rates by 20-25 percentage points; markedly greater increases than predicted from
      a third e-mail reminder. In the gastroenterology sample, the mean number of
      response errors made by web responders (0.25) was significantly smaller than the
      mean number made by postal responders (2.18), and web responders provided
      significantly longer responses to open-ended questions. There were no significant
      differences in these outcomes in the primary care sample. Adequate
      representativeness was achieved before postal follow-up in both samples, as
      indicated by the lack of significant differences between web responders and the
      recruitment population on facility characteristics. We conclude adding postal
      follow-up to this web-based physician leader survey improved response rates but
      not response quality or representativeness. 

PMID- 24318467
TI  - Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast
      cancers from Caucasian women.
AB  - Basal-like and triple-negative breast cancers usually display a high level of
      genomic instability and often carry TP53 mutations. Mutations in EGFR have been
      reported in about 10 % triple-negative tumours from Chinese women, and there is
      some evidence that triple-negative and basal-like tumours might carry additional
      mutations against which targeted therapies are available. We, therefore, sought
      to determine the frequency of 238 targetable mutations in 19 oncogenes (including
      EGFR) in a panel of basal-like and triple-negative breast cancers from Caucasian
      women. We used the OncoCarta panel to screen for 238 mutations across 19 common
      oncogenes in 107 basal-like and triple-negative breast cancers from Caucasian
      women. Mutations were then verified using Sanger sequencing or primer extension
      by iPLEX. We identified and validated 10 mutations across five genes. Most of the
      mutations were observed in the PIK3CA gene (18/107, 16.8 %), while mutations in
      KRAS, NRAS, MET and AKT1 were present in only one tumour each (1/107, 0.9 %).
      Among the missense substitutions in PIK3CA the point mutation resulting in the
      amino acid change H1047R was the most frequent (8/18, 44 %). All mutations were
      mutually exclusive, apart from one basal-like breast tumour which harboured
      mutations in both MET (p.T992I) and PIK3CA (p.H1047R). We did not identify any
      mutations in the EGFR gene. In conclusion, we found that with the exception of
      mutations in PIK3CA, these actionable oncogenic mutations on the Oncocarta panel
      are rare in basal-like and triple-negative breast cancers from Caucasian women.
      Custom panels, designed to detect mutations identified by exome sequencing of
      basal-like and triple-negative breast cancers, are, therefore, needed to identify
      women who might be eligible for targeted treatment. 

PMID- 24318468
TI  - Impact of full-field digital mammography on pre-operative diagnosis and surgical
      treatment of mammographic microcalcification.
AB  - Accurate pre-operative diagnosis of impalpable breast lesions correlates closely
      with the number of surgical procedures required for treatment. Correct diagnosis
      of mammographic microcalcification (MM) as ductal carcinoma in situ (DCIS) or
      invasive breast cancer is important because lesions upgraded to malignant
      diagnosis at surgery require repeat surgical procedures in 44 % of cases. Despite
      correct pre-operative diagnosis of MM, 26 % require second therapeutic operations
      to achieve surgical clearance. Theoretically, improved conspicuity of malignant
      MM using digital mammography could improve diagnostic work-up and improve
      surgical outcomes for MM. To determine the impact of full-field digital
      mammography (FFDM) on the diagnostic accuracy and positive predictive value (PPV)
      of biopsy of MM and surgical management of MM, screening and symptomatic cases
      with MM (n = 1,479) were reviewed for women imaged between August 2007 and March
      2010 using screen-film mammography (SFM) (n = 711), and using FFDM, imaged
      between April 2010 to March 2012 (n = 768). Demographic information including pre
      and postoperative diagnosis, and number and types of surgical procedures were
      recorded. Overall, 302 (128 invasive) and 251 (110 invasive) malignant lesions
      were diagnosed using SFM and FFDM, respectively. Reduction in PPV of biopsy was
      observed (SFM 42.5 %; FFDM 32.7 %, p < 0.001). Correct pre-operative diagnosis
      was achieved at first attempt more often with FFDM (SFM 80.6 %; FFDM 89.5 %, p <
      0.001). For lesions with pre-operative diagnosis, B5 more cases achieved surgical
      clearance with a single therapeutic operation with FFDM (SFM 66.3 %; FFDM 76.7 %,
      p = 0.017), and more lesions over 2 cm underwent mastectomy as the initial
      surgical procedure (SFM 47.0 %; FFDM 62.9 %, p = 0.005). Correct pre-operative
      diagnosis of MM using digital mammography reduced second therapeutic operations
      but increased mastectomy rate in larger cancers over two centimetres. This will
      increase concerns about treatment of lesions detected in the screening programme
      with widespread use of digital mammography. 

PMID- 24318469
TI  - Testing the individual effective dose hypothesis.
AB  - The assumption of the individual effective dose is the basis for the probit
      method used for analyzing dose or concentration-response data. According to this
      assumption, each individual has a uniquely innate tolerance expressed as the
      individual effective dose (IED) or the smallest dose that is sufficient to kill
      the individual. An alternative to IED, stochasticity suggests that individuals do
      not have uniquely innate tolerance; deaths result from random processes occurring
      among similar individuals. Although the probit method has been used extensively
      in toxicology, the underlying assumption has not been tested rigorously. The goal
      of the present study was to test which assumption, IED or stochasticity, best
      explained the response of Daphnia magna exposed to multiple pulses of copper
      sulfate (CuSO4 ) over 24 d. Daphnia magna were exposed to subsequent age
      dependent 24-h median lethal concentrations (LC50s) of copper (Cu). Age-dependent
      24-h LC50 values and Cu depuration test were determined prior to the 24-d
      bioassay. The LC50 values were inversely related to organism age. The Cu
      depuration of D. magna did not depend on age or Cu concentration, and 5 d was
      sufficient recovery time. Daphnia magna were exposed to 4 24-h Cu exposures, and
      surviving organisms after each exposure were transferred to Cu-free culture media
      for recovery before the next exposure. Stochasticity appropriately explained the
      survival and reproduction response of D. magna exposed to Cu.

PMID- 24318470
TI  - Significant improvement in superselective intra-arterial chemotherapy for
      advanced paranasal sinus cancer by using indocyanine green fluorescence.
AB  - Recent advances in indocyanine green (ICG) fluorescence imaging have enabled the
      visualization of the blood supply to tissues. For advanced head and neck cancer,
      intra-arterial chemotherapy has been applied for improving the prognosis and
      organ preservation. To identify the tumor-feeding artery, CT angiography has been
      shown to be useful. However, the presence of dental metals sometimes disturbs the
      precise evaluation of paranasal sinus cancer patients by CT angiography. The
      objectives of the study were to assess the feasibility of the ICG fluorescence
      technique during intra-arterial chemotherapy for advanced maxillary cancer.
      Thirty-six patients with paranasal sinus cancer who were treated by intra
      arterial chemotherapy were included. Conventional CT angiography followed by 5 mg
      of ICG injection was performed to confirm the areas in which the drug had
      dispersed. Intra-arterial chemotherapy was administered at 150 mg/m(2) of CDDP
      four times weekly. Additional information about the arteries feeding the tumors
      provided by ICG was evaluated. Out of 36 cases, in 17 (47%) the blood supply to
      the cancer was clearly detected by CT angiography. By adding the infrared ICG
      evaluation, the blood supply to the tumor was confirmed easily in all cases
      without radiation exposure. The information obtained from fluorescence imaging
      was helpful for making decisions concerning the administration of chemo-agents
      for paranasal sinus cancers in cases involving dental metal, or skin invasion.
      ICG fluorescence imaging combined with intra-arterial chemotherapy compensated
      for the deficiencies of CT angiography for paranasal sinus cancer. ICG
      fluorescence provided us clearer and more useful information about the feeders to
      cancers.

PMID- 24318472
TI  - Attention.

PMID- 24318473
TI  - Understanding religious behavior.
AB  - The attached (to mother) fetus-infant finds his religious expression in Buddhism.
      The attached (to group) juvenile finds his religious expression in Judaism and
      other tribalisms. The attached (to spouse) adult finds his religious expression
      in agnosticism and secularism. Attached phases are placid and of progressively
      decreasing emotional intensity. The three detaching phases are hurtful and hence
      soteriological, and are also of progressively decreasing emotional intensity. The
      toddler-young child finds his religious expression in Christianity, the
      adolescent in atheism and/or Marxism, and the aged, sick or dying plucks at any
      religious or secular aid. 

PMID- 24318471
TI  - Extensive intratemporal cholesteatomas: presentation, complications and surgical
      outcomes.
AB  - The purpose of the study was to review the clinical features, complications,
      surgical management and post-operative outcomes of medially invasive extensive
      cholesteatomas and intracranial complications of cholesteatoma. The retrospective
      review was carried out at a tertiary referral center and included 20 patients
      presenting with extensive intratemporal cholesteatomas between 2011 and 2013.
      Inclusion criteria were involvement of the labyrinth, facial nerve, posterior
      fossa dura and intracranial complications. The mean age of the patients was 20
      years. Profuse foul-smelling otorrhoea and severe otalgia/temporal headache were
      the most common presenting features. Intracranial complications were observed in
      nine patients, most commonly temporal lobe abscess; 14/20 patients exhibited
      profound hearing loss. One case exhibited massive labyrinthine petrous apex
      cholesteatoma. Labyrinthine destruction was seen in all cases of facial nerve
      involvement. Management of intracranial complications preceded canal wall-down
      mastoidectomy with or without partial labyrinthectomy and subtotal petrosectomy
      (transotic) with blind sac closure for petrous cholesteatoma. Facial nerve
      infiltration was observed in one case, whereas eight cases exhibited gross
      dehiscence of the fallopian canal. Disease clearance was complete in all cases
      with two mortalities in patients with intracranial complications. Post-operative
      course was uncomplicated in all other patients apart from a case of wound
      dehiscence. All patients remain disease free after a minimum and maximum follow
      up of 6 months and 2 years, respectively. Extensive intratemporal cholesteatomas
      and intracranial complications caused by them continue to pose a challenge to the
      management of otitis media in the current era and merit early recognition,
      surgical management and follow-up.

PMID- 24318474
TI  - Totemic therapy.
AB  - Totemic therapists, those recognized as healers because of their identification
      with an ethnic subculture, religious group, or social cause, are a factor in
      modern society often overlooked or underestimated as a mental health resource.
      Whatever the advantages and disadvantages of totemic therapy, such therapists
      will be in increasing demand as pluralistic social trends continue. It is
      therefore realistic to ask how their skills may be increased and their services
      better utilized. 

PMID- 24318475
TI  - Nurturing and mythus bearing in clergy work motivation.
AB  - The nature of Protestant clergy work motivation has been unclear. Attempts at
      clarification by clinical, sociological, and theological investigators have not
      been generally accepted. This study hypothesized that positive clergy motivation
      is based upon a preference for anurturing orientation to life and upon
      satisfaction achieved inmythus-bearing work tasks. One hundred and five parish
      ministers of a United Church of Christ Conference in the Middle Atlantic states
      were given the Myers-Briggs Type Indicator and the Work Task Rating Sheet.
      Responses were evaluated according to preferences for feeling and thinking
      orientations and according to satisfaction levels in the performance of work
      tasks. Although three of four specific hypotheses were not supported by
      statistically significant results, enough support was found fornurturing
      preference and satisfaction inmythus bearing to warrant further study of these
      concepts. 

PMID- 24318476
TI  - Cathedral sex.
AB  - Sexual dysfunctions may develop out of relationship problems, from poor or
      ineffective techniques, or from other influences, as overemphasis on performance.
      This article provides a framework for determining the basis of sexual dysfunction
      and offers constructive guidelines for dealing with these sexual problems. 

PMID- 24318477
TI  - An anatomy of hope.
AB  - This paper speaks of hope as a state of being that originates in conditions of
      despair and is transformed as a function of its participation in transcendent
      relationships. In transcendence of self, one establishes the dynamic awareness of
      that peace which enlarges the self to accommodate life's anguish. 

PMID- 24318479
TI  - Gandhi's views on health.

PMID- 24318478
TI  - Cultivating autonomy.
AB  - There exists in every person a desire to control events, to be master of the life
      that surrounds him, to engage the world autonomously. This article argues that
      this desire is peculiarly blind to the intrusion of the uncontrollable or
      unexpected in life, and, when religiously applied, derives from the character
      ofhubris. 

PMID- 24318480
TI  - Pastoral dimensions in death education research.
AB  - During the 1975-1976 school year a project to survey the attitudes of high school
      students regarding death and dying was initiated in Illinois. As the data were
      reviewed, implications for religious leaders became apparent. This manuscript
      summarizes the pertinent findings and introduces some practical considerations
      for church workers. Their involvement in existing death education programs is
      encouraged, and suggestions are made regarding ways for stimulating additional
      attitudinal exploration within their own congregations. The religious
      professional is urged to meet these challenges creatively and sensitively. 

PMID- 24318481
TI  - Analgesic and anti-inflammatory effects of honey: the involvement of autonomic
      receptors.
AB  - The use of honey for therapeutic purposes is on the increase and many studies
      have shown that honey has the ability to influence biological systems including
      pain transmission. Therefore, this study was designed to investigate the
      analgesic and anti-inflammatory effects of honey and the effects of concurrent
      administration of autonomic nervous system blocking drugs. Studies on analgesic
      activities was carried out using hotplate and formalin-induced paw licking models
      while the anti-inflammatory activity was by the carrageenan paw oedema method.
      Animals were distributed into six groups consisting of five animals each. They
      were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic
      blockers (3 MUg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2
      ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200
      and 600 mg/kg) with one of the blockers. The results showed that honey reduced
      pain perception especially inflammatory pain and the administration of tamsulosin
      and propranolol spared the effect of honey. Hexamethonium also spared the effects
      of honey at the early and late phases of the test while atropine only inhibited
      the early phase of the test. However, atropine and hexamethonium spared the anti
      inflammatory effects of honey but tamsulosin abolished the effects while
      propranolol only abolished the anti-inflammatory effects at the peak of the
      inflammation. The results suggest the involvement of autonomic receptors in the
      anti-nociceptive and anti-inflammatory effects of honey although the level of
      involvement depends on the different types of the receptors.

PMID- 24318483
TI  - Erratum to: Clinical Efficacy of a Cosmetic Treatment by Crescina((r)) Human
      Follicle Stem Cell on Healthy Males with Androgenetic Alopecia.

PMID- 24318482
TI  - Enriched environment induces beneficial effects on memory deficits and microglial
      activation in the hippocampus of type 1 diabetic rats.
AB  - Type 1 diabetes mellitus (T1DM) has been associated with long-term complications
      in the central nervous system, causing brain cellular dysfunctions and cognitive
      deficits. On the other hand, enriched environment (EE) induces experience
      dependent plasticity, especially in the hippocampus, improving the performance of
      animals in learning and memory tasks. Thus, our objective was to investigate the
      influence of the EE on memory deficits, locomotion, corticosterone levels,
      synaptophysin (SYP) protein immunoreactivity, cell survival and microglial
      activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats
      (21-day-old) were exposed to EE or maintained in standard housing (controls, C)
      for 3 months. At adulthood, the C and EE animals were randomly divided and
      diabetes was induced in half of them. All the animals received 4 doses of BrdU,
      24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum
      corticosterone levels were evaluated at the end of the experiment. The animals
      were transcardially perfused 30 days post-BrdU administration. Our results showed
      that EE was able to prevent/delay the development of memory deficits caused by
      diabetes in rats, however it did not revert the motor impairment observed in the
      diabetic group. SYP immunoreactivity was increased in the enriched healthy group.
      The EE decreased the serum corticosterone levels in diabetic adult rats and
      attenuated the injurious microglial activation, though without altering the
      decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive
      comorbidities associated with T1DM, possibly by reducing hyperactivity in the
      hypothalamic-pituitary-adrenal axis and microglial activation in diabetic
      animals.

PMID- 24318485
TI  - "Broader impacts" or "responsible research and innovation"?

PMID- 24318486
TI  - Drug resistance mutations and genetic diversity in adults treated for HIV type 1
      infection in Mauritania.
AB  - The aim of this cross-sectional study was to evaluate the drug resistance
      mutationprofile observed in patients receiving antiretroviral therapy with
      virological failure and to document the HIV-1 genetic diversity in Mauritania.
      Eighty-six subjects were included and 65 samples were amplified successfully and
      sequenced. HIV-1 genotyping was performed using the Agence Nationale de Recherche
      sur le SIDA AC11 resistance procedure. The median treatment duration was 32
      months (range: 6-88) and the median viral load, 5 log10 copies/ml (range: 3.13
      7). Fifty-nine patients (90.8%) were on first line regimens including 32.0%
      (19/59) on triomune fixed-dose and six on second-line therapy with NonNucleoside
      Reverse Transcriptase plus a protease inhibitor. Forty-seven patients (72.3%) had
      at least one drug resistance mutation including 73.0% (43/59) on first-line
      therapy. For the second-line, one out of six patients presented resistance
      mutations and only one presented PI DRM. Overall, the most common DRMs detected
      were M184V/I (n = 32; 49.2%), K103N (n = 28; 43%), and Y181C (n = 13; 20%).
      Thymidine Analog Mutations (TAMs) were found in 26.0% (n = 17) of strains and the
      most common was T215Y (n = 11, 16.9%). Phylogenetic analysis revealed 17 HIV-1
      variants with the predominance of CRF02_AG (n = 42; 64.6%). A high rate of DRM
      was found in this study and shows the potential need for a structured virological
      surveillance including viral load quantification and genotyping. Further studies
      may also be needed in regards to the great variability of HIV-1 strains in
      Mauritania.

PMID- 24318487
TI  - Neonatal anthropometrics and body composition in obese children investigated by
      dual energy X-ray absorptiometry.
AB  - Epidemiological and animal studies have suggested an effect of the intrauterine
      milieu upon the development of childhood obesity. This study investigates the
      relationship between body composition measured by dual energy X-ray
      absorptiometry expressed as body fat percent, body fat mass index (BFMI), and fat
      free mass index (FFMI) in obese children and the preceding in utero conditions
      expressed by birth weight, birth length, and birth weight for gestational age.
      The study cohort consisted of 776 obese Danish children (median age 11.6 years,
      range 3.6-17.9) with a mean Body Mass Index Standard Deviation Score (BMI SDS) of
      2.86 (range 1.64-5.48) treated in our national referral centre. In a linear
      general regression model adjusted for age, gender, socioeconomic status, and
      duration of breastfeeding, we found the body fat percent, FFMI, and BFMI at the
      time of enrolment in childhood obesity treatment to be significantly correlated
      with both birth weight and birth weight for gestational age. CONCLUSION: These
      results indicate a prenatal influence upon childhood obesity. Although there are
      currently no sufficient data to suggest any recommendations to pregnant women, it
      is possible that the prenatal period may be considered as a potential window of
      opportunity for prevention of childhood overweight and obesity.

PMID- 24318488
TI  - An unusual case of transient neonatal pustular melanosis: a diagnostic puzzle.
AB  - A newborn's skin may exhibit a variety of changes during the first weeks of life,
      and rashes are extremely common in the neonatal period, representing a
      significant source of parental concern. In particular, a variety of skin
      eruptions can present as pustules. Most of them are innocuous and self-limiting,
      while others can be the manifestation of an infectious disease or even indicative
      of serious underlying disorders. Transient neonatal pustular melanosis is an
      uncommon vesiculopustular rash characterized by small pustules on a non
      erythematous base, noted at birth or during the first day of life, without
      systemic symptoms. The lesions rupture spontaneously, leaving hyperpigmented
      macules that usually fade within few weeks. Clinical recognition of this disease
      can help physicians avoid unnecessary diagnostic testing and treatment for
      infectious etiologies because no specific therapy is recommended. The clinical
      aspect and time of onset are generally sufficient to make the correct diagnosis.
      Nevertheless, peculiar clinical presentations may require additional work-up to
      rule out life-threatening conditions, and dermatological consultation and
      histological examination are required for the final diagnosis. CONCLUSION: We
      report an exceedingly unusual presentation of transient neonatal pustular
      melanosis, suggesting the importance of a systematic diagnostic approach to allow
      a confident recognition of this benign condition.

PMID- 24318489
TI  - Behavioral responses of maleHeliothis zea moths in sustained-flight tunnel to
      combinations of 4 compounds identified from female sex pheromone gland.
AB  - Each of the four compounds that have been identified from sex pheromone glands
      ofHeliothis zea female moths was examined for its ability to elicit sexual
      responses from male moths in a flight tunnel. Males flew upwind to (Z)-11
      hexadecenal alone, but greater levels of behavioral activity were evoked with the
      addition of (Z)-9-hexadecenal to the treatment. Addition of hexadecanal or (Z)-7
      hexadecenal to the initial two components had no effect in raising the behavioral
      response of the males in the flight tunnel whether added singularly at both the
      normal gland-emission ratio or at varying ratios or in combination at the normal
      ratio. Live, calling females elicited levels of sexual activity from males not
      significantly different from that elicited by the mixture of (Z)-11- and (Z)-9
      hexadecenal on cotton wicks. 

PMID- 24318484
TI  - Consensus paper: Language and the cerebellum: an ongoing enigma.
AB  - In less than three decades, the concept "cerebellar neurocognition" has evolved
      from a mere afterthought to an entirely new and multifaceted area of
      neuroscientific research. A close interplay between three main strands of
      contemporary neuroscience induced a substantial modification of the traditional
      view of the cerebellum as a mere coordinator of autonomic and somatic motor
      functions. Indeed, the wealth of current evidence derived from detailed
      neuroanatomical investigations, functional neuroimaging studies with healthy
      subjects and patients and in-depth neuropsychological assessment of patients with
      cerebellar disorders shows that the cerebellum has a cardinal role to play in
      affective regulation, cognitive processing, and linguistic function. Although
      considerable progress has been made in models of cerebellar function, controversy
      remains regarding the exact role of the "linguistic cerebellum" in a broad
      variety of nonmotor language processes. This consensus paper brings together a
      range of different viewpoints and opinions regarding the contribution of the
      cerebellum to language function. Recent developments and insights in the nonmotor
      modulatory role of the cerebellum in language and some related disorders will be
      discussed. The role of the cerebellum in speech and language perception, in motor
      speech planning including apraxia of speech, in verbal working memory, in
      phonological and semantic verbal fluency, in syntax processing, in the dynamics
      of language production, in reading and in writing will be addressed. In addition,
      the functional topography of the linguistic cerebellum and the contribution of
      the deep nuclei to linguistic function will be briefly discussed. As such, a
      framework for debate and discussion will be offered in this consensus paper. 

PMID- 24318490
TI  - Urine fractions that release flehmen in black-tailed deer,Odocoileus hemionus
      columbianus.
AB  - Flehmen (or "lipcurl") is a response of male mammals primarily to female urine,
      performed primarily during the reproductive season. To elucidate the components
      of female urine that release the Flehmen, urine of black-tailed deer (Odocoileus
      hemionus columbianus) was fractionated, and the fractions were presented to
      captive male conspecifics during three rutting seasons. The active principle (one
      or more compounds) is watersoluble, of low volatility, not readily extractable
      with organic solvents, and between 200 and 12,000 daltons in molecular weight.
      Several urine components were identified, but none of these showed activity. 

PMID- 24318491
TI  - Effect of foliage proximity on attraction ofChoristoneura occidentalis andC.
      retiniana (Lepidoptera: Tortricidae) to pheromone sources.
AB  - Pheromone-baited traps located close to both host and nonhost crowns were more
      attractive than traps located between crowns for bothC. occidentalis Freeman
      andC. retiniana (Walsingham) at both 10 m and at 1.5 m above the ground. At 10 m
      height, traps located in host foliage were more attractive than those located in
      nonhost foliage, but at 1.5m height there was no significant difference. These
      results were obtained for both dense and sparse populations ofC. occidentalis and
      sparse populations ofC. retiniana. We conclude that the tree species on which a
      virgin female is located is not an important factor restricting mating between
      closely relatedChoristoneura spp. Also, the tree species on which a trap is
      located may not be an important factor that must be standardized in developing
      pheromone monitoring systems forC. occidentalis andC. retiniana. 

PMID- 24318492
TI  - Plant phenolics as chemical defenses: Effects of natural phenolics on survival
      and growth of prairie voles (Microtus ochrogaster).
AB  - Very few studies have shown experimentally that plant chemical defenses actually
      reduce the performance of individual mammalian herbivores, much less the density
      of mammalian populations. We investigated the effects of representatives of three
      classes of plant phenoiics on the survival and growth of prairie voles by
      incorporating the compounds into artificial diets and feeding them to weanlings
      for three weeks. At low levels of protein, both quercetin (a flavonoid) and
      tannic acid (a hydrolyzable tannin) caused reduced growth rates; no effect
      occurred at high levels of protein. Quebracho (a condensed tannin) inhibited
      feeding and thus was lethal at all levels of protein. These results indicate that
      plant phenolics are likely to influence the performance and dynamics of natural
      populations of microtine rodents by reducing the quality of available forage. The
      hypothesis that the primary mode of action of the phenoiics is the reduction of
      digestibility of protein was not supported. The reduced growth caused by both
      quercetin and tannic acid could be attributed primarily to their toxicity. The
      effect of quebracho resulted from reduced intake (unpalatability). 

PMID- 24318493
TI  - Kairomones and their use for management of entomophagous insects. XV. :
      Identification of several acids in scales ofHeliothis zea moths and comments on
      their possible role as kairomones forTrichogramma pretiosum.
AB  - Acids found in moth scales of laboratory-rearedHeliothis zea (Boddie) moths are
      hexanoic, heptanoic, octanoic, nonanoic, 2- (or 3-) furan carboxylic,
      phenylacetic, benzoic, sorbic, and 4-hydroxybenzoic acid. The last two of these
      acids are preservatives added to the artifical diet as sorbic acid and methyl-p
      hydroxybenzoate. FemaleTrichogramma pretiosum Riley exhibited increased rates of
      parasitization ofH. zea eggs in the presence of some of these compounds in
      laboratory experiments. Exposure to a mixture of all of these compounds did not
      increase parasitization, and the elimination of acids from the crude moth-scale
      extract did not reduce parasitization by the wasps. 

PMID- 24318494
TI  - Effects of dodecyl acetate andZ-10-tridecenyl acetate on attraction ofEupoecilia
      ambiguella males to the main sex pheromone component,Z-9-Dodecenyl acetate.
AB  - Attraction ofE. ambiguella males toZ-9-dodecenyl acetate (Z9-12?Ac), alone and in
      combination with dodecyl acetate (12?Ac) orZ-10-tridecenyl acetate (Z10-13?Ac)
      was tested in both wind-tunnel and field experiments. In the laboratory, response
      toZ9-12?Ac reached a distinct dosage optimum at which attraction was nearly as
      good as to live females. Addition of 12?Ac, a minor component of female glands
      and effluvia, had no effect at low doses ofZ9-12?Ac and only marginally improved
      attraction at the optimum. However, inclusion of 12?Ac with an overdose ofZ9-12?
      Ac fully restored activity. In the field,Z9-12?Ac alone was not very attractive
      at any dose; catches markedly increased by adding 12?Ac and climbed with
      increasing dose of each compound up to 10 mg. Optimum ratio ofZ9-12?Ac to 12?Ac
      was 1?1 to 1?5. Another compound,Z10-13?Ac, had the same effect as 12?Ac in the
      laboratory and the field but was effective at a lower dose. In the field,
      inclusion of the synergist permits use of high cap loads to attract more males,
      perhaps from greater distances. 

PMID- 24318495
TI  - Behavioral effects of secondary components of sex pheromone of western spruce
      budworm (Choristoneura occidentalis) free.
AB  - In a laboratory wind tunnel, upwind flight and close-range orientation to a
      pheromone source by maleC. occidentalis were facilitated by the addition of the
      secondary componentsE/Z11-tetradecen-1-ol acetate (89?11) andE/Z11-tetradecen-1
      ol (85?15) to low source concentrations of the primary components,E/Z11
      tetradecenal (92?8). Male responses to the blends tested never equalled their
      responses to virgin females. The primary components alone, when released at a
      rate similar to that of a "calling" female, never elicited male upwind flight or
      source location. However, the addition of the secondary components enhanced these
      behavioral sequences. 

PMID- 24318496
TI  - Role of pheromone components in evoking behavioral responses from male potato
      tuberworm moth,Phthorimaea operculella (Zeller) (Lepidoptera: Gelechiidae).
AB  - Responses of the male potato tuberworm moth,Phthorimaea operculella (Zeller), to
      two sex pheromone components and female crude extract were studied. Both in a
      wind tunnel and the field, males were better able to locate a source consisting
      of a 1?1 mixture of (E,Z)-4,7-tridecadien-1-yl acetate and (E,Z,Z)-4,7,10
      tridecatrien-1-yl acetate than a source consisting of the triene alone. The
      addition of the diene increased the time spent in the vicinity of the pheromone
      source, time spent on the source itself, and also increased the average number of
      visits to the source per individual when compared to the triene alone. The triene
      elicited high levels of locomotor activity and may play a major role in eliciting
      earlier (long-range) steps in the behavioral sequence of sexually activated
      moths. The diene appeared to influence later (short-range) behavior. The
      behavioral responses of males to a 1?1 mixture of the diene and triene were
      similar to those elicited by female crude extract. 

PMID- 24318497
TI  - Pheromone production by axenically rearedDendroctonus ponderosae andIps
      paraconfusus (Coleoptera: Scolytidae).
AB  - Mountain pine beetles,Dendroctonus ponderosae Hopkins, and California five-spined
      ips,Ips paraconfusus Lanier, were reared axenically from surface-sterilized eggs
      on aseptic pine phloem. After 24 hr in host logs, axenip femaleD. ponderosae and
      maleI. paraconfusus produced the aggregation pheromones,trans-verbenol (D.
      ponderosae), and ipsenol and ipsdienol (I. paraconfusus). Emergent, axenically
      reared maleD. ponderosae contained normal amounts of the pheromoneexo-brevicomin.
      Axenic femaleD. ponderosae treated with juvenile hormone or exposed to vapors of
      alpha-pinene, produced the pheromonetrans-verbenol. By 25-35 days after eclosion,
      axenic females exposed to alpha-pinene vapors produced over six times as
      muchtrans-verbenol as wild females, suggesting that while microorganisms in wild
      females may producetrans-verbenol, they may also inhibit production of the
      pheromone or use it as a substrate. 

PMID- 24318498
TI  - Ethyl (Z)-9-hexadecenoate a sex pheromone ofSyndipnus rubiginosus, a sawfly
      parasitoid.
AB  - A female-produced sex pheromone ofSyndipnus rubiginosus Walley (Hymenoptera:
      Ichneumonidae), a parasitoid of the yellowheaded spruce sawfly,Pikonema
      alaskensis (Rohwer) (Hymenoptera: Tenthredinidae), was isolated and identified
      from hexane extracts of 250 virgin females. Column chromatography (Florisil), gas
      chromatography, mass spectrometry, high performance liquid chromatography, and
      ozonolysis indicated the structure was ethyl (Z)-9-hexadecenoate. The optimum
      male response is at 300-1000 ng (3-10FE). No cross-attraction betweenS.
      rubiginosus and the sympatric sawfly parasitoidS. gaspesianus (Provancher) could
      be demonstrated. 

PMID- 24318499
TI  - Volatile food attractants forOryzaephilus surinamensis (L.) from oats.
AB  - The sawtoothed grain beetle,Oryzaephilus surinamensis (L.) (Coleoptera:
      Cucujidae), is attracted to certain volatile components that occur in whole and
      rolled oats as determined by a laboratory pitfall chamber bioassay. More than 100
      components were detected in the attractive carbonyl-containing fractions; 14 of
      these, making up 60% of the total, were identified and bioassayed. Although
      hexanal, heptanal, octanal, (E)-2-heptenal, and 2-furaldehyde, at doses ranging
      variously from 1 to 100 MUg, were all significantly attractive, only 1 /10 to 1
      /100 as much (E)-2-nonenal or (E,E)-2,4-nonadienal was necessary to produce
      comparable insect response. In addition, propanal and formaldehyde (previously
      reported in oats but not detected by us) were bioassayed and found to be
      attractive. 

PMID- 24318500
TI  - Host selection byBlepharipa pratensis (Meigen), a tachinid parasite of the gypsy
      moth,Lymantria dispar L.
AB  - The host selection process ofBlepharipa pratensis (Meigen), a tachinid parasite
      of the gypsy moth,Lymantria dispar L., was investigated. Once in the host's
      habitat, and following contact with a recently damaged leaf edge (cut, torn,
      eaten), the fly orients perpendicular to the edge and moves back and forth with
      the front tarsi grasping the damaged edge. Oviposturing (oviposition intention)
      may occur. Leaf exudates appear to arrest the fly on the leaf and increase tarsal
      examination (searching). If an edge of a gypsy moth-eaten leaf is contacted,
      oviposition usually occurs. Significantly more eggs are laid when host-browsed
      foliage is encountered, compared to mechanically cut or damaged foliage,
      indicating response to a cue left by the host during feeding. The number of host
      damaged leaf clusters in an area significantly enhances oviposition there; in
      field-cage tests, significantly more eggs (7911) were laid in simulated-crown
      areas with all clusters browsed, compared to the adjacent areas containing 1/2
      browsed (4200 eggs) and undamaged clusters (2209 eggs). A host selection sequence
      is suggested and discussed. 

PMID- 24318501
TI  - Syntheses of unconjugated (Z,Z)-diolefinic insect pheromones on insoluble polymer
      supports.
AB  - A 2% cross-linked styrene-divinylbenzene copolymer containing pendant trityl
      chloride groups was used as the solid support in the synthesis of (Z, Z)-3,13
      octadecadien-1-yl acetate, a component of the sex attractant of the lesser
      peachtree borer,Synanthedon pictipes, the peachtree borer,Synanthedon exitiosa,
      and the cherry tree borer,Synanthedon hector. This solid-phase synthesis is
      compared with a similar synthetic approach in solution. The solid-phase synthesis
      of (Z, Z)-7,11-hexadecadien-1-yl acetate, a component of the pheromone of the
      pink bollworm moth,Pectinophora gossypiella is described. 

PMID- 24318502
TI  - Apparency of pulsed and continuous pheromone to male gypsy moths.
AB  - Quiescent male gypsy moths (Lymantria dispar) exposed in a wind tunnel to either
      pulsed (0.5-, 2- or 5-sec on, followed by a two-fold time interval off) or
      continuous streams of synthetic pheromone responded similarly in the proportions
      and latencies of wing fanning. Similarly, upwind anemotactic flight tracks in
      pulsed (1-sec on and 1-sec off) and continuous plumes of pheromone were
      indistinguishable. These data suggest that in the gypsy moth (1) pulsed pheromone
      stimuli would not lower the threshold, despite the improvement in the signal-to
      noise ratio; and (2) temporal modulation of the pheromone plume at 1-sec
      intervals does not alter the "preprogrammed" upwind flight pattern. 

PMID- 24318503
TI  - Field evaluation of chemical attractants against the flyFannia femoralis
      (Diptera: Muscidae).
AB  - Four chemical compounds previously shown to be attractants toHippelates eye gnats
      and houseflies were evaluated againstFannia femoralis (Stein). Two of the
      compounds, trimethylamine hydrochloride andn-butyric acid, were determined to be
      the principal attractants against this fly. A composition containing
      trimethylamine hydrochloride (yielding trimethylamine in presence of water),n
      butyric acid, and an anchovy meal inert carrier proved highly attractive. To
      evaluate the practical use of the synthetic fly attractant (SFA) formulation, a
      large-scale trial over an entire poultry ranch was implemented using SFA
      formulation and a sugar toxicant (as a killing agent) in specially designed
      traps. Within 2 weeks after initiation of SFA-toxicant treatments, significant
      reduction inF. femoralis population from the pretreatment level occurred. This
      high level of reduction prevailed during the remainder of the treatment period. 

PMID- 24318504
TI  - Zinc-mediated hatching of eggs of soybean cyst nematode,Heterodera glycines.
AB  - Egg hatching of the soybean cyst nematode,Heterodera glycines, was not affected
      by millimolar concentrations of calcium sulfate or calcium chloride. However,
      zinc chloride and zinc sulfate caused strong and moderate increases in hatching,
      respectively. The inhibitors of calcium transport, ruthenium red and lanthanum
      chloride, and calcium ionophore A23187 had no effect on hatching in the presence
      or absence of 3 mM zinc chloride. Selected chelators decreased the zinc-induced
      hatching ofH. glycines eggs. Eggs exhibited a formation constant with zinc
      between 5.5 and 11.2. The addition of zinc chloride after chelation with EDTA and
      rinsing caused expected hatching rates. Concentrations of calcium chloride,
      manganese chloride, and magnesium chloride had no effect on hatching of eggs in
      zinc chloride, but reduced hatching at higher concentrations, possibly by osmotic
      influences. Hatching of eggs was increased as the time of exposure to zinc
      chloride was increased and was maximal at 28  degrees C and a pH of 5.3.
      Picrolonic acid, a known hatching stimulant, increasedH. glycines hatching, while
      sodium metavanadate had no effect. Analysis of seasonal hatching during 1981-1982
      in untreated control eggs indicated that hatching was most pronounced in May. 

PMID- 24318505
TI  - Effect of multilure and its components on parasites ofScolytus multistriatus
      (Coleoptera: Scolytidae).
AB  - Several hymenopterous parasites ofScolytus multistriatus are attracted to
      components of its aggregation pheromone, multilure.Cheiropachus colon, Entedon
      leucogramma, Dendrosoter protuberans, Spathius benefactor, andCerocephala
      eccoptogastri are attracted in various degrees to multilure, its components
      (multistriatin, 4-methyl-3-heptanol, and cubebene), and component combinations.C.
      colon was trapped in greatest numbers, yet was usually less numerous thanE.
      leucogramma andD. protuberans in the study area. Impact of traps onC. colon may
      conceivably be reduced by multistriatin content in baits and/or by withholding
      traps untilS. multistriatus flight begins. 

PMID- 24318506
TI  - Modulation of the fluorescence yield in heliobacterial cells by induction of
      charge recombination in the photosynthetic reaction center.
AB  - Heliobacteria contain a very simple photosynthetic apparatus, consisting of a
      homodimeric type I reaction center (RC) without a peripheral antenna system and
      using the unique pigment bacteriochlorophyll (BChl) g. They are thought to use a
      light-driven cyclic electron transport pathway to pump protons, and thereby
      phosphorylate ADP, although some of the details of this cycle are yet to be
      worked out. We previously reported that the fluorescence emission from the
      heliobacterial RC in vivo was increased by exposure to actinic light, although
      this variable fluorescence phenomenon exhibited very different characteristics to
      that in oxygenic phototrophs (Collins et al. 2010). Here, we describe the
      underlying mechanism behind the variable fluorescence in heliobacterial cells. We
      find that the ability to stably photobleach P800, the primary donor of the RC,
      using brief flashes is inversely correlated to the variable fluorescence. Using
      pump-probe spectroscopy in the nanosecond timescale, we found that illumination
      of cells with bright light for a few seconds put them in a state in which a
      significant fraction of the RCs underwent charge recombination from P800 (+)A0 (
      ) with a time constant of ~20 ns. The fraction of RCs in the rapidly back
      reacting state correlated very well with the variable fluorescence, indicating
      that nearly all of the increase in fluorescence could be explained by charge
      recombination of P800 (+)A0 (-), some of which regenerated the singlet excited
      state. This hypothesis was tested directly by time-resolved fluorescence studies
      in the ps and ns timescales. The major decay component in whole cells had a 20-ps
      decay time, representing trapping by the RC. Treatment of cells with dithionite
      resulted in the appearance of a ~18-ns decay component, which accounted for ~0.6
      % of the decay, but was almost undetectable in the untreated cells. We conclude
      that strong illumination of heliobacterial cells can result in saturation of the
      electron acceptor pool, leading to reduction of the acceptor side of the RC and
      the creation of a back-reacting RC state that gives rise to delayed fluorescence.

PMID- 24318507
TI  - Trends in the diagnosis of SLAP lesions in the US military.
AB  - PURPOSE: Shoulder pathology, particularly SLAP (superior labrum anterior
      posterior) lesions, is prevalent in overhead athletes and physically active
      individuals. The aim of this study is to quantify the burden of SLAP lesions in
      the military and establish risk factors for diagnosis. METHODS: A retrospective
      analysis of all service members diagnosed with a SLAP lesion (International
      Classification of Disease, Ninth Revision code 840.70) in the Defense Medical
      Epidemiological Database between 2002 and 2009 was performed. Available
      epidemiological risk factors including age, sex, race, military rank, and branch
      of service were evaluated using multivariate Poisson regression analysis, and
      cumulative and subgroup incidence rates were calculated. RESULTS: During the
      study period, approximately 23,632 SLAP lesions were diagnosed among a population
      at risk of 11,082,738, resulting in an adjusted incidence rate of 2.13 per 1,000
      person-years. The adjusted annual incidence rate for SLAP lesions increased from
      0.31 cases per 1,000 person-years in 2002 to 1.88 cases per 1,000 person-years in
      2009, with an average annual increase of 21.2 % (95 % CI 20.7 %, 22.0 %, p <
      0.0001) during the study period. Age, sex, race, branch of military service, and
      military rank were independent risk factors associated with the incidence rate of
      SLAP lesion (p < 0.01). Male service members were over twofold more likely (IRR,
      2.12; 95 % CI 2.01, 2.23) to sustain a SLAP lesion when compared with females.
      Increasing age category was associated with a statistically significant increase
      in the incidence rate for SLAP lesions in the present study (p < 0.001). After
      controlling for the other variables, those individuals of white race, enlisted
      ranks, or Marine Corps service experienced the highest incidence rates for SLAP.
      CONCLUSION: This is the first study to establish the epidemiology of SLAP lesions
      within an active military cohort in the American population. Sex, age, race,
      military rank, and branch of military service were all independently associated
      with the incidence rate of SLAP lesions in this physically active population at
      high risk for shoulder injury. LEVEL OF EVIDENCE: II.

PMID- 24318508
TI  - Arthroscopic treatment of acute acromioclavicular joint dislocation by
      coracoclavicular ligament augmentation.
AB  - PURPOSE: Coracoclavicular (CC) ligament augmentation has been a method to treat
      acromioclavicular (AC) joint dislocation in recent years. The purpose of this
      paper is to describe our arthroscopic CC ligament augmentation technique in
      treating type III and V acute AC joint dislocations and to report the early
      clinical and radiological results. METHODS: From 2010 to 2011, twelve patients
      suffering from acute type III or V AC joint dislocations were arthroscopically
      treated in our department, by CC ligament augmentation after AC joint reduction.
      The post-operative outcomes were assessed through physical examination,
      radiographic examination and the Constant-Murley Shoulder Score. RESULTS: All
      patients post-operatively experienced anatomical reduction in their AC joint
      dislocation. No intraoperative complications occurred. At a mean follow-up at 24
      months (ranging from 18 to 32 months), the mean Constant-Murley Shoulder Score
      significantly improved from 24.3 pre-operatively to 91.1 post-operatively. No
      neurovascular complications or secondary degenerative changes of the AC joint
      were detected in any of the patients. In one case, a second dislocation occurred
      1 month post-operation because the patient had had another traumatic injury. This
      patient accepted a revision operation, but his AC joint eventually fixated into a
      subluxated position after his second injury. CONCLUSION: Based on the resultant
      successful repair in all cases, the arthroscopic CC ligament augmentation method
      has thus far proven to be a safe and reliable technique for treatment of acute
      type III or V AC joint dislocation. CLINICAL RELEVANCE: The arthroscopic CC
      ligament augmentation with a flip button/polyethylene belt repair is an efficient
      method to treat acute type III and V AC joint dislocations which should be
      popularized. LEVEL OF EVIDENCE: IV.

PMID- 24318510
TI  - The effect of changing toe direction on knee kinematics during drop vertical
      jump: a possible risk factor for anterior cruciate ligament injury.
AB  - PURPOSE: The purpose of this study was to examine the effect of changing toe
      direction on knee kinetics and kinematics associated with anterior cruciate
      ligament injury during drop vertical jumps. METHODS: Fourteen females performed
      drop vertical jumps under three toe conditions (natural, toe-in, and toe-out).
      The knee kinetics and kinematics during landing were evaluated using a motion
      analysis system. Results under three toe conditions were compared using a one-way
      repeated measures analysis of variance and a post hoc Bonferroni test. RESULTS:
      Toe-in landing was associated with a significantly greater knee abduction angle,
      tibial internal rotation angle, and knee abduction moment than the natural and
      toe-out conditions. Toe-out landing was associated with significantly greater
      tibial internal rotational angular velocity. CONCLUSIONS: Changing toe direction
      significantly affects knee kinetics and kinematics during landing. It is
      important to avoid changing toe direction excessively inward or outward during
      landing to prevent the increases in knee abduction and tibial internal rotation
      which might increase the risk of ACL injury. LEVEL OF EVIDENCE: Prognosis, Level
      IV.

PMID- 24318509
TI  - Outcomes after ACL reconstruction with focus on older patients: results from The
      Swedish National Anterior Cruciate Ligament Register.
AB  - PURPOSE: To investigate and analyse outcomes of patients over the age of 40 who
      had undergone anterior cruciate ligament (ACL) reconstruction and to compare them
      to their younger counterparts. We analysed patient-reported outcomes measured
      using the knee injury and osteoarthritis outcome score (KOOS) as well as
      aetiology of injury, concomitant intra-articular injuries and time from injury to
      surgery. METHODS: Data were extracted from the Swedish National Knee Ligament
      Register during the period of 2005 through 2012. The following data were
      extracted and analysed: patient age, gender, activity at the time of injury, time
      between injury and reconstruction, concomitant intra-articular injuries, graft
      size used for reconstruction and KOOS measured pre-operatively as well as 1, 2
      and 5 years post-operatively. The cohort was stratified into age groups of 0-19,
      20-29, 30-39 and >= 40 years of age. RESULTS: Pivoting sports were dominating as
      the cause of ACL injury in the younger age groups (up to 39 years). Alpine skiing
      and other non-specified activities were the most common causes in the older age
      group (>= 40 years). Pre-operative KOOS was significantly lower in older age
      groups (p < 0.01). Post-operative KOOS regarding all subscales was significantly
      better in the older age group. The improvement in KOOS was significant with
      increasing age (p < 0.01). Older patients exhibited the greatest improvement in
      KOOS for all subscales at 1, 2 and 5 years post-operative follow-ups compared
      with pre-operative values (p < 0.01). Older patients had more cartilage injuries
      pre-operatively compared with younger patients. The same trend was observed in
      the older group for meniscus injury with and without cartilage injuries. The
      diameter of the graft used for ACL reconstruction was significantly larger in the
      older age groups and largest in the age group >= 40 years (p < 0.01). Older
      patients waited significantly longer for surgery after the ACL injury (p < 0.01).
      CONCLUSION: In the older age groups, patients reported lower pre-operative KOOS
      compared with their younger counterparts. At follow-up, KOOS was similar in all
      age groups. From these results, we can therefore conclude that our hypothesis
      confirmed that optimal surgical results can in fact be achieved even in older
      patients.

PMID- 24318511
TI  - Spontaneous regression of restenosis after CEA: significance of preoperative
      plaque characteristics under duplex ultrasound; clinical investigation.
AB  - BACKGROUND: Restenosis is a postoperative complication after carotid
      endarterectomy (CEA). The natural clinical course of restenotic lesions is not
      yet fully understood. This study was aimed at detecting the pattern of restenotic
      lesions by way of following the plaque thickness under duplex ultrasound, and the
      possible relationship between the postoperative changes of restenotic lesions and
      the preoperative plaque characteristics. METHOD: Serial duplex ultrasound follow
      up studies were conducted postoperatively, and intima-media thickness (IMT) was
      measured to detect restenosis changes. Among 381 cases of CEA, including 25 cases
      of restenosis, 11 were eligible for further analysis. FINDINGS: Of the 11 cases
      of restenosis, four showed a gradual increase in IMT, and five showed a temporary
      increase followed by a decrease in IMT. All cases in the former group showed
      isoechogenic or hypoechogenic plaques under preoperative duplex ultrasound. In
      contrast, all cases in the latter group demonstrated calcified plaques together
      with acoustic shadows. CONCLUSIONS: These postoperative chronological IMT data
      demonstrate two changing patterns of restenosis, implying the existence of two
      distinct entities. In addition, these results suggest that restenosis after
      removal of a calcified plaque, which supposedly forms secondary to myointimal
      hyperplasia, may be a temporary phenomenon that acutely develops in response to a
      dissection maneuver during surgery. Because our speculation is based on a small
      number of cases, further study is warranted to better understand the
      pathophysiology of restenosis regression.

PMID- 24318512
TI  - The epidemiology of adult traumatic brachial plexus lesions in a large
      metropolis.
AB  - INTRODUCTION: Adult traumatic brachial plexus lesions are devastating injuries.
      Their real incidence is difficult to ascertain, but are certainly growing due to
      the increasing number of high-speed motor-vehicle accidents, especially in big
      cities. OBJECTIVES: Analysis of the epidemiological characteristics of patients
      with traumatic brachial plexus lesions in Sao Paulo, Brazil, the sixth largest
      city in the world. METHODS: This was a retrospective analysis of the
      epidemiological characteristics of patients submitted to surgical treatment of
      traumatic brachial plexus lesions in the Peripheral Nerve Surgery Unit of the
      Department of Neurosurgery of the University of Sao Paulo Medical School.
      RESULTS: In the period from 2004 to 2012, 406 patients underwent surgery. There
      were 384 (94.6 %) men and 22 (5.4 %) women. In 45.9 % the compromised plexus was
      the right and in 54.1 %, the left. The average age was 28.38 years. Among the
      causes, the most frequent was motorcycle accidents (79 %). Most of the lesions
      were supraclavicular. In 46.1 % of cases the lesions were complete, in 30.1 % the
      lesions compromised C5/C6 roots, in 20.9 % the C5/C6/C7 roots were lesioned and
      in 2.9 % the lesion was in the lower roots, C8/T1. Among the associated lesions
      the most prevalent were head trauma, observed in 34.2 % of the cases; lesions of
      long bones in 38.8 %; clavicle fractures in 25.9 %; and thoracic trauma in 12.9
      %. CONCLUSION: In a population of adult patients with brachial plexus lesions
      with surgical indication, most of them comprise young male adults involved in
      high-energy motorcycle accidents.

PMID- 24318515
TI  - The paratendineous tissues: an anatomical study of their role in the pathogenesis
      of tendinopathy.
AB  - The aim of this paper was to examine the macroscopic and microscopic
      characteristics of the paratendineous tissues (paratenon, epitenon and endotenon)
      of the calcaneal tendon to better understand their role in the pathogenesis of
      "tendinopathy". Ten non-embalmed legs from cadavers were used. Histological and
      immunohistochemical studies were done at the middle third of the tendon. Magnetic
      resonance images of the hind foot were made in 60 living subjects to analyze the
      morphological alterations of tendon and paratenon. The paratenon is a thick
      fibrous layer with few elastic fibers, continuous with the crural fascia, well
      vascularized and innervated. It forms a sheath around the tendon similar to a
      synovial layer, but less organized. Indeed, it has no complete epithelium, but
      only some cells producing hyaluronan, called fasciacytes. Crural fascia and
      paratenon can be clearly observed by MRI, appearing as homogeneous, low signal
      intensity bands, sharply defined in the context of subcutaneous tissue in T1
      weighted sequences. The mean thickness of the crural fascia was 1.11 mm in
      healthy subjects and 1.30 mm in patients (p < 0.005). The mean value of paratenon
      thickness in patients was 1.34 mm, 0.85 in healthy (p < 0.0001). The paratenon is
      more highly vascularized and innervated than the tendon, supporting the
      hypothesis that it is the origin of pain in tendinopathy. The imaging study
      suggests that, an increase in the thickness of the paratenon more than 1.35 mm is
      predictive of paratendinopathy, even before tendon damage.

PMID- 24318516
TI  - Effect of training and familiarity on responsiveness to human cues in domestic
      dogs (Canis familiaris).
AB  - Domestic dogs (Canis familiaris) seem to possess an evolved competency to follow
      human-given cues, often out-performing their wild progenitor the wolf (Canis
      lupus) on cue-following tasks. However, domestication may not be solely
      responsible for the socio-cognitive skills of dogs, with ontogenetic experience
      also playing a role. This research evaluated the effects of intensive training on
      cue-following behaviour using an unreinforced object-choice paradigm. The
      responses of dogs that were trained to competitive levels were compared to those
      of pet dogs with only basic training, and dogs living in an animal shelter that
      demonstrated no or only rudimentary following of basic commands. Using a cue
      following task where three types of cues were presented by familiar and
      unfamiliar human partners, the number of cues followed by each training group
      were recorded. All dogs found cues where gesture was combined with a congruent
      head and eye movement easier to follow than either gesture or eye gaze alone.
      Whether the cue-giver was familiar or not had a significant effect on number of
      cues followed in homed dogs, and the performance of shelter dogs was comparable
      to the other groups when faced with an unfamiliar cue-giver. Contrary to
      predictions, level of training did not improve performance on the cue-following
      task. This work does provide support for the presence of an evolved adaptation to
      exploit social cues provided by humans that can be augmented by familiarity with
      the cue giver. However, additional joint activity as experienced in an intensive
      training regime does not seem to increase accuracy in following human-given cues.

PMID- 24318514
TI  - Common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated
      with gout susceptibility.
AB  - Gout is a common disease resulting from hyperuricemia which causes acute
      arthritis. Recently, genome-wide association studies revealed an association
      between serum uric acid levels and a common variant of leucine-rich repeat
      containing 16A (LRRC16A) gene. However, it remains to be clarified whether
      LRRC16A contributes to the susceptibility to gout. In this study, we investigated
      the relationship between rs742132 in LRRC16A and gout. A total of 545 Japanese
      male gout cases and 1,115 male individuals as a control group were genotyped.
      rs742132 A/A genotype significantly increased the risk of gout, conferring an
      odds ratio of 1.30 (95 % CI 1.05-1.60; p = 0.015). LRRC16A encodes a protein
      called capping protein ARP2/3 and myosin-I linker (CARMIL), which serves as an
      inhibitor of the actin capping protein (CP). CP is an essential element of the
      actin cytoskeleton, which binds to the barbed end of the actin filament and
      regulates its polymerization. In the apical membrane of proximal tubular cells in
      the human kidney, the urate-transporting multimolecular complex (urate
      transportsome) is proposed to consist of several urate transporters and
      scaffolding proteins, which interact with the actin cytoskeleton. Thus, if there
      is a CARMIL dysfunction and regulatory disability in actin polymerization, urate
      transportsome may be unable to operate appropriately. We have shown for the first
      time that CARMIL/LRRC16A was associated with gout, which could be due to urate
      transportsome failure.

PMID- 24318513
TI  - Regulation of plasticity and fibrogenic activity of trabecular meshwork cells by
      Rho GTPase signaling.
AB  - Glaucoma, a prevalent blinding disease is commonly associated with increased
      intraocular pressure due to impaired aqueous humor (AH) drainage through the
      trabecular meshwork (TM). Although increased TM tissue contraction and stiffness
      in association with accumulation of extracellular matrix (ECM) are believed to be
      partly responsible for increased resistance to AH outflow, the extracellular cues
      and intracellular mechanisms regulating TM cell contraction and ECM production
      are not well defined. This study tested the hypothesis that sustained activation
      of Rho GTPase signaling induced by lysophosphatidic acid (LPA), TGF-beta, and
      connective tissue growth factor (CTGF) influences TM cell plasticity and
      fibrogenic activity which may eventually impact resistance to AH outflow. Various
      experiments performed using human TM cells revealed that constitutively active
      RhoA (RhoAV14), TGF-beta2, LPA, and CTGF significantly increase the levels and
      expression of Fibroblast Specific Protein-1 (FSP-1), alpha-smooth muscle actin
      (alphaSMA), collagen-1A1 and secretory total collagen, as determined by q-RT-PCR,
      immunofluorescence, immunoblot, flow cytometry and the Sircol assay.
      Significantly, these changes appear to be mediated by Serum Response Factor
      (SRF), myocardin-related transcription factor (MRTF-A), Slug, and Twist-1, which
      are transcriptional regulators known to control cell plasticity, myofibroblast
      generation/activation and fibrogenic activity. Additionally, the Rho kinase
      inhibitor-Y27632 and anti-fibrotic agent-pirfenidone were both found to suppress
      the TGF-beta2-induced expression of alphaSMA, FSP-1, and collagen-1A1. Taken
      together, these observations demonstrate the significance of RhoA/Rho kinase
      signaling in regulation of TM cell plasticity, fibrogenic activity, and
      myofibroblast activation, events with potential implications for the pathobiology
      of elevated intraocular pressure in glaucoma patients.

PMID- 24318517
TI  - Synthesis of Cu(I) trifluoromethylselenates for trifluoromethylselenolation of
      aryl and alkyl halides.
AB  - The development of new strategies for synthesis of trifluoromethylthiolate
      compounds is of considerable importance in pharmaceuticals, agrochemicals, and
      advanced materials. Accordingly, currently much attention is being devoted to the
      development of effective methods and reagents for their synthesis. In contrast,
      considerably less effort has been afforded to the development of preparing
      C?SeCF3 bonds. Herein we report a concise route to synthesize a family of
      copper(I) trifluoromethylselenolate reagents by the reaction of CuI with the
      Ruppert's reagent (Me3 SiCF3 ), KF, and elemental selenium in the presence of
      dinitrogen ligands in CH3 CN at room temperature. The reagent [Cu(bpy)(SeCF3 )]2
      was proven to be air-stable and highly efficient for nucleophilic
      trifluoromethylthselenolation of a broad range of (hetero)aryl halides and alkyl
      halides. This method represents a powerful protocol for the construction
      trifluoromethylselenolate compounds. 

PMID- 24318519
TI  - Correlation of the coronary severity scores and mean platelet volume in diabetes
      mellitus.
AB  - INTRODUCTION: It is known that mean platelet volume (MPV) increases during acute
      coronary syndrome. However, there are conflicting data about the importance of
      MPV in patients with stable coronary artery disease (CAD). This study aimed to
      assess relationship between MVP and the severity of coronary atherosclerosis in
      patients with diabetes mellitus (DM), stable CAD and normal left ventricular
      ejection fractions. METHODS: Thirty-three DM and 46 nonDM patients with stable
      CAD diagnosed by selective coronary angiography were included in the study. All
      angiographic variables pertinent to Gensini score (GS) and Syntax score (SS)
      calculation were computed by two experienced interventional cardiologists. All
      patients underwent echocardiographic examination. MPV and other biochemical
      markers were measured on admission. RESULTS: All patients were evaluated and it
      was found that both scoring systems are correlated with MPV (GS: r = 0.373, p <
      0.001; SS: r = 0.385, p < 0.001). DM and nonDM groups were severally evaluated,
      it was found that the correlation between MPV and GS and SS increased in DM
      patients (GS: r = 0.638, p < 0.001; SS: r = 0.624, p < 0.001); however, no
      differences were identified in nonDM patients (GS: r = 0.124, p = 0.410; SS: r =
      0.124, p = 0.411). CONCLUSION: It is thought that high MPV levels may be an
      effective marker in determining the severity of CAD in patients with DM. And the
      high MPV level may be related with CAD pathophysiology in DM patients.

PMID- 24318518
TI  - Lactose consuming strains of Xanthomonas citri subsp. citri (Xcc) insight into
      the emergence of natural field resources for xanthan gum production.
AB  - Xanthomonas genus possesses a low level of beta-galactosidase gene expression and
      is therefore unable to produce xanthan gum in lactose-based media. In this study,
      we report the emergence of some natural field strains of Xanthomonas citri subsp.
      citri (Xcc) capable to use lactose as a sole carbon source to produce xanthan
      gum. From 210 Xcc strains isolated from key lime (C. aurantifolia), 27 showed the
      capacity to grow on lactose containing medium. Xcc lactose consuming strains
      demonstrated a good level of xanthan production. Amongst all, NIGEBK37 produced
      the greatest (14.62 g/l) amount of xanthan gum in experimental laboratory
      conditions. By evaluating the viscosity of the biopolymer at 25  degrees C, it
      was demonstrated that xanthan synthesized by strain NIGEBK37 has the highest
      viscosity (44,170.66 cP). Our results were indicative for the weakness of a
      commercial strain of Xanthomonas campestris pv. Campestris DSM1706 (Xcc/DSM1706)
      to produce xanthan in lactose containing medium. 

PMID- 24318520
TI  - New technology: safety, efficacy, and learning curves.

PMID- 24318522
TI  - Questions that matter.

PMID- 24318523
TI  - The sense of life time in human development.
AB  - The subjective sense oflife time is the medium within which issues of identity
      and growth take place. Youth, middle age, early old age, and old age are each
      presented as developmental stages with dominant experiences oflife time.
      Directivity, or purposeful movement toward a goal, is then related to the
      experience of future and occurs in the gap between present and future. The sense
      of "now" in old age is viewed as a stage in the life cycle with the potential for
      unique personal creativity and growth, being free from bondages found at other
      points in the life cycle. 

PMID- 24318524
TI  - Meditation to fit the person: Psychology and the meditative way.
AB  - Only lately having recovered their bodies and feelings, Western devotees of
      various meditative practices are in increasing numbers striving to transcend
      both. Is such a turning inward healthy for individuals and our society? A full
      response requires both a clarifying discussion of exactly what meditation is and
      a review of its effects. Meditation, essentially a way of life, is marked by four
      stages: preparation, attention, active reception, and higher consciousness. Even
      though the Western traditions aim finally at union with the Infinite and Eastern
      traditions seek primarily an internal unity through the negation of
      consciousness, both describe essentially the same four stages, reached through
      the meditative pathways of the intellect, emotions, body, and action. Present
      scientific research is only beginning to provide data on the effects of
      meditation upon the person. To date, most research findings point out
      psychophysiological changes during meditation, indicating a low-stress state.
      Meditative experience lends support to the conclusion that successful meditation
      also positively affects growth by touching man's inner life source, expanding his
      consciousness, and revealing personal life directions. 

PMID- 24318525
TI  - Toward an understanding of the obese person.
AB  - Attitudes, feelings, and family backgrounds of seven very obese women were
      studied by means of a religious history questionnaire. Some comments are made
      about this research tool. Three very prominent characteristics of these women
      were feelings of helplessness and powerlessness, a craving for love, and strong
      guilt feelings. A possible psychogenic factor in morbid obestity was observed in
      the backgrounds of five women; pertinent information on the other two was
      lacking. This factor is a dual dynamic of harshness and indulgence. The onset of
      obesity seemed to occur when indulgence became the dominating influence over
      harshness. 

PMID- 24318526
TI  - Homosexuality, the Halacha, and the helping professions.
AB  - The position of Jewish writings on homosexuality is the topic of inquiry. Overt
      homosexuality, child homosexuality, and lesbianism are examined in the light of
      Jewish Halacha (law). Though Talmudic writings view homosexuality with severe
      disapproval, a sprrit of tolerance and compassion is also voiced in them. It is
      suggested here that Jewish law placed overt homosexuality in the category of
      illness to evoke compassion for it Halachic insights also suggest that
      homosexualities be viewed differentially. Activities involving minors and
      lesbians are not given equal weight in the realm of retribution. There are
      efforts to obviate social stigma. Prevention and rehabilitation are given major
      concern. To conclude the article, the role of the Jewish religious practitioner
      and his responsibilities vis-a-vis the homosexual client are given a brief
      examination. 

PMID- 24318527
TI  - The dynamics of creation.
AB  - A basic question in any great religion is, "What is the source of creation, how
      did order emerge from disorder, or how did we get here?" Among the myths proposed
      is the Genesis account of an original creation from a condition "without form and
      void" by a supernatural creator. Now the sciences reveal a more cogent
      explanation, a new myth of the process of self-creation in an evolutionary
      continuity of being. Instead of an external power of creation, my thesis is that
      a generalized concept of love as a generic power of attraction is the dynamics of
      creation. 

PMID- 24318528
TI  - The ego dilemma and the Buddhist experience of enlightenment.
AB  - The author examines the core problem of existence, the dread of nonbeing, from
      the standpoint of object-relations theory and subsequently demonstrates that the
      experience of enlightenment, emerging from religious mysticism, may be seen as
      the resolution of this basic human problem. The investigation of the experience
      of enlightenment is pursued from the perspective of Buddhism, a subject with
      which the author is most familiar. 

PMID- 24318529
TI  - Combining the roles of "Priest" and "physician": A clinical case.
AB  - In antiquity the healing role was usually performed by one person-a "priest
      physician." This also applied to hypnotism. As science emerged, eventually the
      roles of physician and priest were separated and performed by different persons.
      In the present case the roles of "priest" and "physician" were again united,
      resulting in significant improvement for the patient. Previously the separated
      roles had been ineffective. 

PMID- 24318530
TI  - 111th DOG (German ophthalmological society) congress Berlin 19-22 september 2013.

PMID- 24318531
TI  - Clinical features of IgG4-related dacryoadenitis.
AB  - BACKGROUND: To elucidate the clinical characteristics of IgG4-related
      dacryoadenitis. METHODS: Clinical features, laboratory findings, radiological
      findings, associated diseases, treatment, and prognosis were prospectively
      examined in 12 patients (seven men, five women; mean age, 60.9 +/- 15.1 years)
      with IgG4-related dacryoadenitis. RESULTS: In addition to eyelid swelling, other
      ophthalmologic symptoms were observed in seven patients, including diplopia (n =
      4), ptosis (n = 2), visual field disturbance (n = 2), eye pain (n = 2), decrease
      of visual acuity (n = 2), eye-movement disturbance (n = 1), dry eye (n = 1),
      corneal ulcer (n = 1), and epiphora (n = 1). Swelling of the lacrimal glands was
      bilateral in half of the patients. Other IgG4-related diseases were present in
      nine patients, including sialadenitis (n = 5), autoimmune pancreatitis (n = 4),
      retroperitoneal fibrosis (n = 2), and lymphadenopathy (n = 8). Serum IgG4 levels
      were significantly higher in patients with other IgG4-related disease (1070 +/-
      813 mg/dl) than in those without (197 +/- 59 mg/dl, p = 0.017). Allergic
      histories and elevated serum IgE levels were each detected in six patients. Eight
      patients showed inflammatory extension beyond the lacrimal gland, such as
      thickened rectus muscle (n = 6), inflammation of the optic nerve (n = 2), and
      retrobulbar inflammation (n = 3). Steroid therapy was effective in seven
      patients, but dacryoadenitis relapsed in two patients with markedly higher serum
      IgG4 levels and autoimmune pancreatitis. CONCLUSIONS: IgG4-related dacryoadenitis
      showed various ophthalmologic symptoms due to extensive inflammation beyond the
      lacrimal gland, frequent association with other IgG4-related disease or allergic
      phenomena, and steroid responsiveness.

PMID- 24318532
TI  - An unexpected link between notch signaling and ROS in restricting the
      differentiation of hematopoietic progenitors in Drosophila.
AB  - A fundamental question in hematopoietic development is how multipotent
      progenitors achieve precise identities, while the progenitors themselves maintain
      quiescence. In Drosophila melanogaster larvae, multipotent hematopoietic
      progenitors support the production of three lineages, exhibit quiescence in
      response to cues from a niche, and from their differentiated progeny. Infection
      by parasitic wasps alters the course of hematopoiesis. Here we address the role
      of Notch (N) signaling in lamellocyte differentiation in response to wasp
      infection. We show that Notch activity is moderately high and ubiquitous in all
      cells of the lymph gland lobes, with crystal cells exhibiting the highest levels.
      Wasp infection reduces Notch activity, which results in fewer crystal cells and
      more lamellocytes. Robust lamellocyte differentiation is induced even in N
      mutants. Using RNA interference knockdown of N, Serrate, and neuralized (neur),
      and twin clone analysis of a N null allele, we show that all three genes inhibit
      lamellocyte differentiation. However, unlike its cell-autonomous function in
      crystal cell development, Notch's inhibitory influence on lamellocyte
      differentiation is not cell autonomous. High levels of reactive oxygen species in
      the lymph gland lobes, but not in the niche, accompany N(RNAi)-induced
      lamellocyte differentiation and lobe dispersal. Our results define a novel dual
      role for Notch signaling in maintaining competence for basal hematopoiesis: while
      crystal cell development is encouraged, lamellocytic fate remains repressed.
      Repression of Notch signaling in fly hematopoiesis is important for host defense
      against natural parasitic wasp infections. These findings can serve as a model to
      understand how reactive oxygen species and Notch signals are integrated and
      interpreted in vivo.

PMID- 24318533
TI  - Three potato centromeres are associated with distinct haplotypes with or without
      megabase-sized satellite repeat arrays.
AB  - We report discoveries of different haplotypes associated with the centromeres of
      three potato chromosomes, including haplotypes composed of long arrays of
      satellite repeats and haplotypes lacking the same repeats. These results are in
      favor of the hypothesis that satellite repeat-based centromeres may originate
      from neocentromeres that lack repeats. 

PMID- 24318534
TI  - Identifying signatures of selection in genetic time series.
AB  - Both genetic drift and natural selection cause the frequencies of alleles in a
      population to vary over time. Discriminating between these two evolutionary
      forces, based on a time series of samples from a population, remains an
      outstanding problem with increasing relevance to modern data sets. Even in the
      idealized situation when the sampled locus is independent of all other loci, this
      problem is difficult to solve, especially when the size of the population from
      which the samples are drawn is unknown. A standard chi(2)-based likelihood-ratio
      test was previously proposed to address this problem. Here we show that the
      chi(2)-test of selection substantially underestimates the probability of type I
      error, leading to more false positives than indicated by its P-value, especially
      at stringent P-values. We introduce two methods to correct this bias. The
      empirical likelihood-ratio test (ELRT) rejects neutrality when the likelihood
      ratio statistic falls in the tail of the empirical distribution obtained under
      the most likely neutral population size. The frequency increment test (FIT)
      rejects neutrality if the distribution of normalized allele-frequency increments
      exhibits a mean that deviates significantly from zero. We characterize the
      statistical power of these two tests for selection, and we apply them to three
      experimental data sets. We demonstrate that both ELRT and FIT have power to
      detect selection in practical parameter regimes, such as those encountered in
      microbial evolution experiments. Our analysis applies to a single diallelic
      locus, assumed independent of all other loci, which is most relevant to full
      genome selection scans in sexual organisms, and also to evolution experiments in
      asexual organisms as long as clonal interference is weak. Different techniques
      will be required to detect selection in time series of cosegregating linked loci.

PMID- 24318535
TI  - The novel secreted factor MIG-18 acts with MIG-17/ADAMTS to control cell
      migration in Caenorhabditis elegans.
AB  - The migration of Caenorhabditis elegans gonadal distal tip cells (DTCs) offers an
      excellent model to study the migration of epithelial tubes in organogenesis. mig
      18 mutants cause meandering or wandering migration of DTCs during gonad
      formation, which is very similar to that observed in animals with mutations in
      mig-17, which encodes a secreted metalloprotease of the ADAMTS (a disintegrin and
      metalloprotease with thrombospondin motifs) family. MIG-18 is a novel secreted
      protein that is conserved only among nematode species. The mig-17(null) and mig
      18 double mutants exhibited phenotypes similar to those in mig-17(null) single
      mutants. In addition, the mutations in fbl-1/fibulin-1 and let-2/collagen IV that
      suppress mig-17 mutations also suppressed the mig-18 mutation, suggesting that
      mig-18 and mig-17 function in a common genetic pathway. The Venus-MIG-18 fusion
      protein was secreted from muscle cells and localized to the gonadal basement
      membrane, a tissue distribution reminiscent of that observed for MIG-17.
      Overexpression of MIG-18 in mig-17 mutants and vice versa partially rescued the
      relevant DTC migration defects, suggesting that MIG-18 and MIG-17 act
      cooperatively rather than sequentially. We propose that MIG-18 may be a cofactor
      of MIG-17/ADAMTS that functions in the regulation of the gonadal basement
      membrane to achieve proper direction of DTC migration during gonadogenesis. 

PMID- 24318536
TI  - Evidence for paternal age-related alterations in meiotic chromosome dynamics in
      the mouse.
AB  - Increasing age in a woman is a well-documented risk factor for meiotic errors,
      but the effect of paternal age is less clear. Although it is generally agreed
      that spermatogenesis declines with age, the mechanisms that account for this
      remain unclear. Because meiosis involves a complex and tightly regulated series
      of processes that include DNA replication, DNA repair, and cell cycle regulation,
      we postulated that the effects of age might be evident as an increase in the
      frequency of meiotic errors. Accordingly, we analyzed spermatogenesis in male
      mice of different ages, examining meiotic chromosome dynamics in spermatocytes at
      prophase, at metaphase I, and at metaphase II. Our analyses demonstrate that
      recombination levels are reduced in the first wave of spermatogenesis in juvenile
      mice but increase in older males. We also observed age-dependent increases in XY
      chromosome pairing failure at pachytene and in the frequency of prematurely
      separated autosomal homologs at metaphase I. However, we found no evidence of an
      age-related increase in aneuploidy at metaphase II, indicating that cells
      harboring meiotic errors are eliminated by cycle checkpoint mechanisms,
      regardless of paternal age. Taken together, our data suggest that advancing
      paternal age affects pairing, synapsis, and recombination between homologous
      chromosomes--and likely results in reduced sperm counts due to germ cell loss-
      but is not an important contributor to aneuploidy.

PMID- 24318537
TI  - Internalizing behaviours in school-age children born very preterm are predicted
      by neonatal pain and morphine exposure.
AB  - BACKGROUND: Greater neonatal pain is associated with higher internalizing
      behaviours in very preterm infants at 18 months corrected age, but it is unknown
      whether this relationship persists to school age. Moreover, it is unclear whether
      morphine ameliorates or exacerbates the potential influence of neonatal
      pain/stress on internalizing behaviours. We examined whether neonatal pain
      related stress is associated with internalizing behaviours at age 7 years in
      children born very preterm, and whether morphine affects this relationship.
      METHODS: One hundred one children born very preterm (<=32 weeks gestation) were
      seen at mean age 7.7 years. A parent completed the Parenting Stress Index and
      Child Behavior Checklist questionnaires. Neonatal pain-related stress (the number
      of skin-breaking procedures adjusted for clinical factors associated with
      prematurity) was examined in relation to internalizing behaviour, separately in
      subjects mechanically ventilated and exposed to both pain and morphine (n = 57)
      and those never mechanically ventilated, exposed to pain but not morphine (n =
      44). RESULTS: In the non-ventilated group, higher skin-breaking procedures (p =
      0.037) and parenting stress (p = 0.004) were related to greater internalizing
      behaviours. In the ventilated group, greater morphine exposure (p = 0.004) was
      associated with higher child internalizing scores. CONCLUSIONS: In very preterm
      children who undergo mechanical ventilation, judicious use of morphine is
      important, since morphine may mitigate the negative effects of neonatal pain on
      nociception but adversely affect internalizing behaviours at school age.
      Management of procedural pain needs to be addressed in very preterm infants in
      the neonatal intensive care unit, to prevent long-term effects on child
      behaviour.

PMID- 24318538
TI  - Hemodynamic analysis of renal artery stenosis using computational fluid dynamics
      technology based on unenhanced steady-state free precession magnetic resonance
      angiography: preliminary results.
AB  - This study aims to evaluate the feasibility of computational fluid dynamics (CFD)
      technology in analysis of renal artery stenosis (RAS) based on unenhanced MR
      angiography (MRA). Thirty hypertensive patients with unilateral RAS, and 10
      normal volunteers, underwent unenhanced MRA on a 1.5 T MR scanner. 12 of 30
      patients also underwent ultrasound (US) to detect peak systolic velocity. The
      patient-specific CFD based on MRA was carried out thereafter. Stenosis grades and
      hemodynamic variables at the stenosis of main renal artery, including pressure
      difference (PD), velocity and mass flow rate (MFR), were analysed. And the
      hemodynamic indices of stenoses were compared with the parameters of normal renal
      arteries and available US velocity profile. High intraclass correlation
      coefficient (value 0.995) and no significant difference (p > 0.05) was shown
      between maximum velocity of CFD and peak systolic velocity of US in 12 patients.
      For normal renal arteries, the average PD, velocity and MFR were all in the
      reported normal physiological range. However, for stenotic arteries, the
      translesional PD and velocity of main renal arteries increased with the severity
      of stenotic degrees, while the MFR decreased. 50 % diameter stenosis was the
      threshold at which all three hemodynamic parameters experienced significant
      changes (p < 0.01). This preliminary study shows that unenhanced-MRA-based CFD
      can be utilized to noninvasively analyse hemodynamic parameters of RAS. The
      acquired variables may provide meaningful information regarding stratification of
      the stenosis and further therapeutic treatment.

PMID- 24318539
TI  - Evaluation of fall armyworm resistance in maize germplasm lines using visual leaf
      injury rating and predator survey.
AB  - After examining ear-colonizing pest resistance, 20 maize lines from the USDA-ARS
      Germplasm Enhancement of Maize (GEM) Program were evaluated for whorl-feeding
      fall armyworm (FAW) (Spodoptera frugiperda) resistance using 4 maize inbred lines
      as the resistant and susceptible controls. Both FAW injury ratings at 7- and 14-d
      after infestation, and predator abundance and diversity at whorl stage (V6-V8)
      were recorded in 2009 and 2010. The survey of the diversity and abundance of
      predators in each experimental plot were conducted 7 d after the FAW infestation.
      Of the 20 germplasm lines examined, 3 of them (i.e., entries 9, 15, and 19 that
      were derived from tropical maize germplasm lines were originated from Uruguay,
      Cuba, and Thailand, respectively) were identified as the best FAW-resistant
      germplasm lines using the leaf injury ratings and predator survey data. In
      addition, the abundance and diversity of the predators were greater in 2010 than
      in 2009, which might have caused the low level of the FAW injury ratings on all
      lines examined in 2010. The 2-year data showed that the FAW injury ratings were
      negatively correlated to the predator abundance and diversity, which is also
      influence by genotype * environment interactions. The findings suggested that
      tropical germplasm is an important source of native resistance to the FAW and the
      corn earworm. At the same time, the maize genotype * environment interaction
      (e.g., predator attractiveness, and varying weather conditions) should be
      included in the multiple-year evaluations of insect and disease resistance of
      maize germplasm lines under field conditions.

PMID- 24318541
TI  - Incidence, risk factors, and implemented prophylaxis of varicella zoster virus
      infection, including complicated varicella zoster virus and herpes simplex virus
      infections, in lenalidomide-treated multiple myeloma patients.
AB  - In the era of high-dose chemotherapy and novel antimyeloma agents, the survival
      of multiple myeloma (MM) patients has substantially improved. Adverse effects,
      including infections, may however arise in the era of combination antimyeloma
      therapies. In general, MM patients have shown a risk of varicella zoster virus
      (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants,
      but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes
      simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection
      [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here
      assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients,
      consecutively seen and treated in our department. Patients' data were analyzed
      via electronic medical record retrieval within our research data warehouse as
      described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV
      or other complicated VZV/HSV infections. These VZV patients showed defined risk
      factors as meticulously assessed, including suppressed lymphocyte subsets,
      substantial cell-mediated immune defects, and compromised humoral immune
      response. Due to our findings-and in line with an aciclovir prophylaxis in
      bortezomib and stem cell transplant protocols-we introduced a routine aciclovir
      prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events
      and to avoid discontinuation of lenalidomide treatment. Since then, we have
      observed no case of VZV/complicated HSV infection. Based on our data, we
      encourage other centers to also focus on these observations, assess viral
      infections, and-in those centers facilitating a research data warehouse-advocate
      an analogue data review as an appropriate multicenter approach.

PMID- 24318542
TI  - Seed germination, root elongation, root-tip mitosis, and micronucleus induction
      of five crop plants exposed to chromium in fluvo-aquic soil.
AB  - The present study aimed to determine the toxic effects of chromium (Cr) on
      cabbage (Brassica oleracea), cucumber (Cucumis sativus), lettuce (Lactuca
      sativa), wheat (Triticum aestivum), and corn (Zea mays), and identify the
      sensitive plant species and appropriate bioassays for potential use in
      phytotoxicity assessment of Cr in soil. Results showed that seed germination
      might not be a sensitive assay for assessing Cr toxicity because at most of the
      Cr levels there were no toxic effects. Root elongation was more sensitive to Cr
      than seed germination. The lowest concentration of adverse effect (LOAEC) of
      lettuce was 20 mg Cr/kg(-1) soil, and that of the other 4 species was 50 mg
      Cr/kg(-1) soil. The mitotic index fluctuated with increasing Cr concentration,
      thus it was insufficient to assess toxicity of Cr in soil. However, micronucleus
      assay showed that 5 mg Cr/kg(-1) soil caused a significant increase in
      micronucleus frequency in cabbage, cucumber, and lettuce. For wheat and corn,
      however, the LOAEC was 20 and 50 mg/Cr/kg(-1) soil, respectively. Furthermore,
      the analysis of Cr accumulation showed that lettuce significantly accumulated Cr
      for all the tested concentrations. However, corn and wheat significantly
      accumulated Cr only with the highest tested dose. This may explain the higher
      inhibitory effects of Cr on root growth. It can be concluded that root elongation
      and micronucleus assay are good indicators to assess the phytotoxicity of Cr in
      soil. Lettuce is the most sensitive species for indicating the toxicity of Cr in
      soil.

PMID- 24318543
TI  - Fetal vibroacoustic stimulation for facilitation of tests of fetal wellbeing.
AB  - BACKGROUND: Acoustic stimulation of the fetus has been suggested to improve the
      efficiency of antepartum fetal heart rate testing. OBJECTIVES: To assess the
      advantages and disadvantages of the use of fetal vibroacoustic stimulation in
      conjunction with tests of fetal wellbeing. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013).
      SELECTION CRITERIA: All published and unpublished randomised controlled trials
      assessing the merits of the use of fetal vibroacoustic stimulation in conjunction
      with tests of fetal wellbeing. DATA COLLECTION AND ANALYSIS: All review authors
      independently extracted data and assessed trial quality. Authors of published and
      unpublished trials were contacted for further information. MAIN RESULTS:
      Altogether 12 trials with a total of 6822 participants were included. Fetal
      vibroacoustic stimulation reduced the incidence of non-reactive antenatal
      cardiotocography test (nine trials; average risk ratio (RR) 0.62, 95% confidence
      interval (CI) 0.48 to 0.81). Vibroacoustic stimulation compared with mock
      stimulation evoked significantly more fetal movements when used in conjunction
      with fetal heart rate testing (one trial, RR 0.23, 95% CI 0.18 to 0.29). AUTHORS'
      CONCLUSIONS: Vibroacoustic stimulation offers benefits by decreasing the
      incidence of non-reactive cardiotocography and reducing the testing time. Further
      randomised trials should be encouraged to determine not only the optimum
      intensity, frequency, duration and position of the vibroacoustic stimulation, but
      also to evaluate the efficacy, predictive reliability, safety and perinatal
      outcome of these stimuli with cardiotocography and other tests of fetal
      wellbeing.

PMID- 24318540
TI  - Glutamate and its receptors in the pathophysiology and treatment of major
      depressive disorder.
AB  - Monoaminergic neurotransmitter (serotonin, norepinephrine and dopamine)
      mechanisms of disease dominated the research landscape in the pathophysiology and
      treatment of major depressive disorder (MDD) for more than 50 years and still
      dominate available treatment options. However, the sum of all brain neurons that
      use monoamines as their primary neurotransmitter is <20%. In addition, most
      patients treated with monoaminergic antidepressants are left with significant
      residual symptoms and psychosocial disability not to mention side effects, e.g.,
      sexual dysfunction. In the past several decades, there has been greater focus on
      the major excitatory neurotransmitter in the human brain, glutamate, in the
      pathophysiology and treatment of MDD. Although several preclinical and human
      magnetic resonance spectroscopy studies had already implicated glutamatergic
      abnormalities in the human brain, it was rocketed by the discovery that the N
      methyl-D-aspartate receptor antagonist ketamine has rapid and potent
      antidepressant effects in even the most treatment-resistant MDD patients,
      including those who failed to respond to electroconvulsive therapy and who have
      active suicidal ideation. In this review, we will first provide a brief
      introduction to glutamate and its receptors in the mammalian brain. We will then
      review the clinical evidence for glutamatergic dysfunction in MDD, the discovery
      and progress-to-date with ketamine as a rapidly acting antidepressant, and other
      glutamate receptor modulators (including proprietary medications) for treatment
      resistant depression. We will finally conclude by offering potential future
      directions necessary to realize the enormous therapeutic promise of glutamatergic
      antidepressants.

PMID- 24318544
TI  - Fetal manipulation for facilitating tests of fetal wellbeing.
AB  - BACKGROUND: Manual fetal manipulation has been suggested to improve the
      efficiency of antepartum fetal heart rate testing. OBJECTIVES: The objective of
      this review was to assess the merits or adverse effects of the use of manual
      fetal manipulation in conjunction with tests of fetal wellbeing. SEARCH METHODS:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30
      September 2013). SELECTION CRITERIA: All published and unpublished randomised
      controlled trials assessing the use of fetal manipulation versus mock
      stimulation, no stimulation or other types of stimulation, used in conjunction
      with cardiotocography or other tests of fetal wellbeing. DATA COLLECTION AND
      ANALYSIS: Three review authors independently assessed studies for inclusion,
      assessed trial quality and extracted data. Data were checked for accuracy. We
      contacted authors of published and unpublished trials for further information.
      MAIN RESULTS: We included four trials with a total of 1280 women with 2670
      episodes of participation. No trial was at low risk of bias for all domains and
      only two trials were at low risk of bias for both selection and attrition
      bias.Fetal manual manipulation decreased the incidence of non-reactive antenatal
      cardiotocography test compared to mock or no stimulation. However, this was not
      statistically significant (average risk ratio (RR) 0.31, 95% confidence interval
      (CI) 0.02 to 6.20, I2 = 96%; two trials, N = 2350). There was also no significant
      reduction in the mean testing time to achieve a reactive result (mean difference 
      2.29 minutes, 95% CI -9.61 minutes to 5.03 minutes, I2 = 97%; two trials, N =
      560).Comparing fetal manual manipulation with vibroacoustic stimulation, there
      was no significant difference in the incidence of non-reactive cardiotocography
      or the need for contraction-stress test.There were no data available on other
      outcomes such as perinatal mortality, fetal distress, maternal anxiety and
      gestation at delivery. AUTHORS' CONCLUSIONS: There is insufficient evidence to
      support the use of manual fetal manipulation during cardiotocography or other
      tests of fetal wellbeing. More studies of manual fetal manipulation that utilises
      standardised protocol should be encouraged.

PMID- 24318546
TI  - Factors affecting levels of some phenolic compounds, digestibility, and nitrogen
      content of the mature leaves ofBarteria fistulosa (Passifloraceae).
AB  - Levels of total phenolics, condensed tannins, acid detergent fiber,
      pepsin/cellulase digestibility, and nitrogen in mature leaves of 26 individuals
      of the ant-plant,Barteria fistulosa, have been determined. Analysis of the
      results in terms of the presence or absence of ants and the position of the
      branch from which the leaves were collected showed no relationship with
      concentrations of phenolics or fiber and only a weak relationship with
      digestibility and nitrogen. By contrast, light intensity strongly influenced
      levels of phenolics, notably condensed tannins, so that mature leaves of
      individuals growing in direct sunlight were less digestible and appeared to be of
      lower quality as food for herbivores than did mature leaves of individuals in
      shaded positions. Possible reasons for the variation in condensed tannin levels
      are discussed. 

PMID- 24318547
TI  - Misidentification by wild rabbits,Oryctolagus cuniculus, of group members
      carrying the odor of foreign inguinal gland secretion : III. Experiments with
      mixed sex groups and analysis of further data from all-male and all-female
      groups.
AB  - The experiments described in this paper are part of a series designed to clarify
      the behavioral function of the odor of the secretion from the inguinal glands of
      rabbits,Oryctolagus cuniculus. Results are presented of tests carried out on 48
      mixed-sex groups consisting of 162 adult wild-type rabbits, 48 males and 114
      females. The subordinate females of the groups were smeared with various odorous
      materials and the reactions of their pen-mates towards them recorded. Eight
      sources of natural rabbit odors and a commercial perfume were used in 198 tests.
      A high proportion (60%) of the subordinate females smeared with the inguinal
      gland secretions from unfamiliar males were attacked, mainly by the males, which
      were generally the most dominant individuals within the groups. The paper also
      presents statistical analyses of behavioral data collected during two earlier
      related experiments with single-sex groups involving 258 rabbits in 300 tests
      which have not previously been evaluated. The results throughout the whole study
      indicate clearly that the odor of the inguinal gland secretion of rabbits carries
      information which affects the acceptance of individuals by their companions in
      organized groups. Other sources of unfamiliar rabbit odor did not influence the
      attitude of groupmates toward the individuals smeared with them, or if they did,
      their effects were only marginal. 

PMID- 24318548
TI  - Trimerization ofEarias insulana sex pheromone, (E,E)-10,12-Hexadecadienal, A
      phenomenon affecting trapping efficiency.
AB  - The sex pheromone ofEarias insulana, (E,E)-10,12-hexadecadienal, may trimerize
      extensively to form a crystalline trioxane derivative. The structure of the
      trimer was deduced from its CI-MS and NMR spectra. Capillary GC analysis resulted
      in the thermal decomposition of the trimer to the monomer. This process could be
      studied on a 2-m packed column under specific conditions. A convenient separation
      between the pheromone and its trimer was achieved by TLC. The trimer was inactive
      in the field, and it has a harmful effect on the performance of the polyethylene
      dispenser. Material which contains large amounts of the trimer is unsuitable for
      field use, even if applied at high dosage. The pheromone should be analyzed by
      NMR or TLC in addition to GC in order to detect the presence of its trimer. The
      trimerization process is catalyzed by acid which should therefore be completely
      eliminated from the storing vessels. 

PMID- 24318549
TI  - Contact sex pheromone in the tsetse flyGlossina pallidipes (Austen)
      Identification and Synthesis.
AB  - Adult maleG. pallidipes attempted to copulate with decoys treated with a branched
      paraffin obtained from laboratory-reared female flies. The compound causing
      maximal response was isolated and identified as 13,23-dimethylpentatriacontane.
      The synthesized compound elicited increasing responses with increasing doses.
      This sex- and species-specific compound was always present in physiological
      amounts in females, as it increased from 2 MUg at emergence to 10 MUg per female
      at 14 days. It was present in wild-caught females from a wide geographical range.

PMID- 24318545
TI  - Inhibitory and multisynaptic spines, and hemispherical synaptic specialization in
      the posterodorsal medial amygdala of male and female rats.
AB  - The density of dendritic spines is sexually dimorphic and variable throughout the
      female estrous cycle in the rat posterodorsal medial amygdala (MePD), a relevant
      area for the modulation of reproductive behavior in rats. The local synaptic
      activity differs between hemispheres in prepubertal animals. Here we used serial
      section transmission electron microscopy to produce 3D reconstructions of
      dendritic shafts and spines to characterize synaptic contacts on MePD neurons of
      both hemispheres in adult males and in females along the estrous cycle.
      Pleomorphic spines and nonsynaptic filopodia occur in the MePD. On average, 8.6%
      of dendritic spines received inputs from symmetric gamma-aminobutyric acid (GABA)
      immunoreactive terminals, whereas 3.6% received two synaptic contacts on the
      spine head, neck, or base. Presynaptic terminals in female right MePD had a
      higher density of synaptic vesicles and docked vesicles than the left MePD,
      suggesting a higher rate of synaptic vesicle release in the right MePD of female
      rats. In contrast, males did not show laterality in any of those parameters. The
      proportion of putative inhibitory synapses on dendritic shafts in the right MePD
      of females in proestrus was higher than in the left MePD, and higher than in the
      right MePD in males, or in females in diestrus or estrus. This work shows
      synaptic laterality depending on sex and estrous cycle phase in mature MePD
      neurons. Most likely, sexual hormone effects are lateralized in this brain
      region, leading to higher synaptic activity in the right than in the left
      hemisphere of females, mediating timely neuroendocrine and social/reproductive
      behavior.

PMID- 24318550
TI  - Chemistry of cephalic secretion of fire beeTrigona (Oxytrigona) tataira.
AB  - Analysis of the volatile compounds derived from cephalic glands of the fire
      beeTrigona (Oxytrigona) tataira by GC-MS was undertaken. The following compounds
      were readily identified: hydrocarbons:n-C11H24,n-C13H28,n-C14H30,n-C15H32,n
      C17H36,n-C23H48,n-C15H30,n-C17H34,n-C21 H42, andn-C23H46; carboxylic acids:
      palmitic acid, linoleic acid, linolenic acid, stearic acid, and oleic acid;
      carboxylic esters: dodecyl acetate, tetradecyl acetate, hexadecyl acetate,
      octadecyl acetate, and dodecyl decanoate; monoketones: 5-hepten-2-one, 3-hepten-2
      one, 2-heptanone, and 5-nonen-2-one. Two major components of the mixture were
      identified asE-hepten-2,5-dione andE-3-nonen-2,5-dione. Structures of these novel
      compounds were suggested by their GC-MS behavior and the GC-MS behavior of their
      dimethoximes and proved by comparison with authentic synthetic samples. Trace
      amounts of the corresponding Z isomers and the saturated analogs, heptan-2,5
      dione and nonan-2,5-dione, were also found. The possible functions of these
      glandular constituents are discussed. 

PMID- 24318551
TI  - Novel sex pheromone components from the fall cankerworm moth,Alsophila pometaria.
AB  - A sex pheromone extract from fall cankerworm moths,Alsophila pometaria, attracted
      conspecific males in field tests. Four EAG-active components were isolated from
      the extract and identified by GC-MS, highfield PMR spectroscopy, and
      microchemical techniques asn-nonadecane (I), (Z,Z,Z)-3,6,9-nonadecatriene (II),
      (Z,Z,Z,E)-3,6,9,11-nonadecatetraene (III), and (Z,Z,Z,Z)-3,6,9,11-nonadecatetrane
      (IV). Studies of the behavioral responses of male moths in a flight tunnel to the
      isolated components showed II, III, and IV were the major components of the sex
      pheromone. No sex pheromone behavioral responses were observed for I. 

PMID- 24318552
TI  - Defensive behavior and toxicity of ascoglossan opisthobranchMourgona germaineae
      marcus.
AB  - The ascoglossan (= sacoglossan) opisthobranchMourgona germaineae Marcus secretes
      a viscid mucus and autotomizes cerata when mechanically disturbed. Other small
      invertebrates, i.e., sea anemones, amphipods, and other ascoglossans, will die
      when placed with these autotomized cerata or in the water in which they have been
      autotomized. The toxin is methanol-soluble and water-soluble and thus is probably
      a small molecule. Simultaneous TLC of chloroform and methanol-water extracts ofM.
      germaineae and of its food alga,Cymopolia barbata indicates that the toxin is
      most likely of dietary origin. 

PMID- 24318553
TI  - Insect predator-prey coevolution via enantiomeric specificity in a kairomone
      pheromone system.
AB  - Insect predators can be guided to their prey by a kairomonal response to the prey
      pheromone. We found this phenomenon to be highly specific in the bark beetle
      predatorThanasimus dubius. Olfactory responses and behavioral tests revealed that
      the predator is guided to its major preyDendroctonusfrontalis by the primary
      enantiomer of the pheromone of the prey, (1S, 5R)-(-)-frontalin. These and other
      findings suggest the co-evolution of a kairomone system of the predator and the
      pheromone system of its prey. 

PMID- 24318554
TI  - Comparison of tannin levels in developing fruit buds of two orchard pear
      varieties using two techniques, Folin-Denis and protein precipitation assays.
AB  - As part of a study into dietary selection by avian pest species, the levels of
      phenolic material in pear buds have been determined using two approaches, the
      Folin-Denis assay and an assay based on the precipitation of bovine serum albumin
      by astringent phenols. The results of these two assays do not correlate over the
      sampling period and their overall significance to ecological studies is
      discussed. 

PMID- 24318555
TI  - Distribution of birch (Betula SPP.), willow (Salix SPP.), and poplar (Populus
      SPP.) secondary metabolites and their potential role as chemical defense against
      herbivores.
AB  - Isoprenoids and phenolics, major metabolites of important browse species, are
      reviewed in regard to concentrations, distribution within tissues, and between
      species. Seasonal variation of specific substances and changes with age of the
      plant are also considered. The distribution of substances may affect food
      selection and feeding behavior of animals. Wild mammalian herbivores tend to
      avoid plant parts rich in these substances, in spite of high nutritional content
      of the plant tissue. Possible mechanisms for defense by plants against
      depredation by mammalian herbivores are discussed within the framework of the
      plants' biochemistry. 

PMID- 24318556
TI  - Behavioral and biological responses ofCotesia marginiventris to kairomones of the
      fall armyworm,Spodoptera frugiperda.
AB  - Potential kairomone sources of the fall armyworm (FAW),Spodoptera frugiperda
      (J.E. Smith), were bioassayed with females ofCotesia marginiventris (Cresson) in
      Petri dishes (10 cm diam). MatedC. marginiventris females, ranging in age from 1
      to 3 days exhibited the most intense bioassay responses to potential sources of
      kairomone. Contacting a FAW-damaged corn leaf modified the pattern of movement
      inC. marginiventris from random to one exhibiting a significant increase in
      klinokinesis. No significant differences were present in kairomone responses of
      nonconditioned and conditioned parasitoids and parasitoid response to kairomones
      did not change throughout the photophase (0800-1800 hr). Removal of one, both, or
      the first eight antennal segments reduced or eliminated the response of the
      parasitoid to kairomones. Female parasitoids did not exhibit a preference for
      corn leaves damaged by a particular fall armyworm instar and parasitization rates
      were highest in larvae 48 hr old. 

PMID- 24318557
TI  - Chemical composition and efficacy of cephalic gland secretion ofArmitermes
      chagresi (Isoptera: Termitidae).
AB  - Soldiers of the neotropical humivorous termiteArmitermes chagresi have large ice
      tong-like mandibles for mechanical defense and a moderate length nasus from which
      cephalic gland defensive secretions are discharged. Soldiers do not eject
      secretion, but ooze droplets which are held at the nasus tip by hairs. The
      chemical secretion is composed of C22-C26 macrocyclic lactones, including C24 and
      C26 and alpha- and beta-hydroxylated lactones, with C24 macrolides predominating.
      The cephalic gland secretion has no pheromonal properties and does not induce
      alarm or attraction in soldiers or workers. Upon application, the secretion
      repels and is irritating to ants, but does not appear to act as an antihealant.
      The defensive behavior and chemistry ofA. chagresi is discussed in light of
      termite ecology and evolution. 

PMID- 24318559
TI  - Cerebellum and neuropsychiatric disorders: insights from ARSACS.
AB  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare
      neurodegenerative disorder characterized by ataxia, spastic paraparesis,
      polyneuropathy, and evidence of superior cerebellar vermis atrophy at magnetic
      resonance imaging (MRI). Reports of atypical presentations and additional
      clinical or MRI findings have been recently published, but psychiatric
      disturbances have never been associated with ARSACS. We describe four ARSACS
      patients manifesting severe psychiatric symptoms including psychosis, panic
      disorder, and depression during the course of the disease. Our case reports
      further expand the ARSACS phenotype and add clinical data in favor of the
      hypothesized relationship between cerebellar dysfunction and psychiatric
      disorders. 

PMID- 24318561
TI  - Inaccuracies in the recently published review on mirabegron.

PMID- 24318560
TI  - Intra-operative 5-aminolevulinic acid (ALA)-induced fluorescence of
      medulloblastoma: phenotypic variability and CD133(+) expression according to
      different fluorescence patterns.
AB  - 5-Aminolevulinic acid (5-ALA) fluorescence has been proved advantageous in glioma
      surgery. Conflicting results have been reported by few studies published in
      literature about intra-operative 5-ALA-induced fluorescence of medulloblastoma
      (MDB). The aim of this study is to verify if these conflicting results could be
      explained by intra-tumoral histological and phenotypic differences. In the
      present case of a 45-year-old patient affected by a cerebellar MDB, histological
      analysis of cell phenotype and 5-ALA and CD133 correlation were performed in
      multiple samples according to different fluorescence patterns. Intra-operatively,
      the tumor appeared unevenly fluorescent under blue-violet light. Histologically,
      5-ALA-intense biopsies from inner areas were characterized by a significant
      amount of cancer cells, whereas 5-ALA faint regions from peripheral areas
      displayed normal cerebellar features, with MDB cells infiltrating healthy
      tissues. Presenting our findings, we show the correlation between different 5-ALA
      fluorescence patterns of medulloblastoma with specific histological and
      phenotypical features. Thus, we hypothesize that a distinct relationship between
      CD133 expression and fluorescence accumulation presented in our study could
      partially explain the divergent results published in literature.

PMID- 24318562
TI  - Immunohistochemical analysis of estrogen receptors in the urethra of sexually
      intact, ovariectomized, and estrogen-substituted ovariectomized sheep.
AB  - INTRODUCTION AND HYPOTHESIS: Urinary incontinence is prevalent in postmenopausal
      women and spayed dogs and is associated with decreased estrogen plasma
      concentrations. The objective of the study was to investigate the expression of
      estrogen receptors (ER) in the urethra of sexually intact, ovariectomized, and
      estrogen-substituted ovariectomized ewes. METHODS: Paraffin cross-sections from
      each urethral quarter were immunohistochemically analyzed. The reactivity of ER
      was semiquantitatively assessed employing an immunoreactive score (IRS). RESULTS:
      In contrast to ERbeta, ERalpha was identified in all urethral compartments; the
      highest IRS was detected in the epithelium of the distal urethra. The
      immunoreactivity and distribution of ERalpha did not differ among groups. Highly
      significant differences in ERalpha concentrations were observed between
      consecutive urethral quarters in each group. CONCLUSIONS: Neither ovariectomy nor
      ovariectomy and estrogen substitution seem to have a significant effect on
      overall urethral ERalpha concentration. The results demonstrate that the precise
      location of the investigated urethral part is crucial to the reliable evaluation
      or possible comparison of ERalpha concentrations.

PMID- 24318563
TI  - Reinforcement of suspensory ligaments under local anesthesia cures pelvic organ
      prolapse: 12-month results.
AB  - INTRODUCTION AND HYPOTHESIS: In 2005, a new minimally invasive procedure, the
      tissue fixation system (TFS) was reported. Like TVT (tension-free vaginal tape),
      the TFS works by creating a foreign body collagenous tissue reaction that
      reinforces a weakened pelvic ligament. The objective was to assess the
      effectiveness and perioperative safety of TFS in a day surgery clinic for the
      treatment of pelvic organ prolapse (POP). METHODS: The TFS tape was applied in a
      tunnel adjacent to natural ligaments to repair the anterior cervical ring and
      cardinal ligament, paravaginal tissues and uterosacral ligaments under local
      anesthesia/sedation. We prospectively studied 60 patients, mean age 67, between
      October 2008 and February 2010 at Women's Clinic LUNA. Levels of POP were grade 2
      (n = 20; 7 %), grade 3 (n = 30; 55 %), and grade 4 (n = 4; 7 %) according to the
      ICS POPQ classification. Fifty-four patients (90 %) who underwent a total of 162
      POP operations presented for review. Follow-up was performed at 12 months. We
      defined surgical failure according to the ICS POPQ classification. We used
      prolapse quality of life (P-QOL) questions for QOL measurement. RESULTS: Ninety
      eight percent of patients were discharged on the day of surgery. Of the 162 TFS
      operations reviewed, 157 were successful and 5 failed. The 5 failed operations
      comprised 4 cystoceles and 1 rectocele. Two patients developed cervical
      protrusions at the introitus at 6 months with no prolapse of the uterine body. We
      found 5 cases of erosion in 162 tape insertions. The total number of patients who
      had no complications, no surgical failures, no erosions, no sensation of bulging,
      and no cervical protrusions was 47 (87 %). CONCLUSIONS: The TFS uses the same
      surgical principle for repair as the TVT; this principle vastly minimizes the
      volume of mesh used, erosions, and other complications.

PMID- 24318564
TI  - Outcomes following treatment for pelvic floor mesh complications.
AB  - INTRODUCTION AND HYPOTHESIS: Our aim was to determine symptoms and degree of
      improvement in a cohort of women who presented following treatment for vaginal
      mesh complications. METHODS: This study was a follow-up to a multicenter,
      retrospective study of women who presented to four tertiary referral centers for
      management of vaginal-mesh-related complications. Study participants completed a
      one-time follow-up survey regarding any additional treatment, current symptoms,
      and degree of improvement from initial presentation. RESULTS: Two hundred and
      sixty women received surveys; we had a response rate of 41.1 % (107/260).
      Complete data were available for 101 respondents. Survey respondents were more
      likely to be postmenopausal (p = 0.006), but otherwise did not differ from
      nonrespondents. Fifty-one percent (52/101) of women underwent surgery as the
      primary intervention for their mesh complication; 8 % (4/52) underwent a second
      surgery; 34 % (17/52) required a second nonsurgical intervention. Three patients
      required three or more surgeries. Of the 30 % (30/101) of respondents who
      reported pelvic pain prior to intervention, 63 % (19/30) reported improvement, 30
      % (9/30) were worse, and 7 % (2/30) reported no change. Of the 33 % (33/101) who
      reported voiding dysfunction prior to intervention, 61 % (20/33) reported being
      at least somewhat bothered by these symptoms. CONCLUSIONS: About 50 % of women
      with mesh complications in this study underwent surgical management as treatment,
      and <10 % required a second surgery. Most patients with pain preintervention
      reported significant improvement after treatment; however, almost a third
      reported worsening pain or no change after surgical management. Less than half of
      patients with voiding dysfunction improved after intervention.

PMID- 24318565
TI  - Competitive gold-activation modes in terminal alkynes: an experimental and
      mechanistic study.
AB  - The competition between pi- and dual sigma,pi-gold-activation modes is revealed
      in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable
      effect of various ligands in gold complexes on the choice of these activation
      modes is described. The cationic [Au(IPr)](+) (IPr=2,6
      bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes the pi
      activation of terminal alkynes, whereas [Au(PtBu3 )](+) favors intermediate
      sigma,pi species. In this experimental and mechanistic study, which includes
      kinetic and cross-over experiments, several sigma-gold, sigma,pi-gold, and other
      gold polynuclear reaction intermediates have been isolated and identified by NMR
      spectroscopy, X-ray diffraction, or MALDI spectrometry. The ligand control in the
      simultaneous or alternative pi- and sigma,pi-activation modes is also supported
      by deuterium-labeling experiments. 

PMID- 24318566
TI  - Low-temperature spectroscopy of bacteriochlorophyll c aggregates.
AB  - Chlorosomes from green photosynthetic bacteria belong to the most effective light
      harvesting antennas found in nature. Quinones incorporated in bacterichlorophyll
      (BChl) c aggregates inside chlorosomes play an important redox-dependent photo
      protection role against oxidative damage of bacterial reaction centers.
      Artificial BChl c aggregates with and without quinones were prepared. We applied
      hole-burning spectroscopy and steady-state absorption and emission techniques at
      1.9 K and two different redox potentials to investigate the role of quinones and
      redox potential on BChl c aggregates at low temperatures. We show that quinones
      quench the excitation energy in a similar manner as at room temperature, yet the
      quenching process is not as efficient as for chlorosomes. Interestingly, our data
      suggest that excitation quenching partially proceeds from higher excitonic states
      competing with ultrafast exciton relaxation. Moreover, we obtained structure
      related parameters such as reorganization energies and inhomogeneous broadening
      of the lowest excited state, providing experimental ground for theoretical
      studies aiming at designing plausible large-scale model for BChl c aggregates
      including disorder. 

PMID- 24318567
TI  - Septic arthritis: patients with or without isolated infectious agents have
      similar characteristics.
AB  - PURPOSE: Septic arthritis can be disabling and life-threatening, requiring prompt
      diagnosis and treatment. The infectious agent is not always identified in these
      patients. We revaluate septic arthritis cases discharged from our department,
      describing the affected population, causative microorganisms and antibiotic
      therapy used, and characterised differences between patients with and without
      isolated pathogenic agents. METHODS: Sixty-eight septic arthritis patients were
      included in this study. Diagnosis was based on clinical findings, and/or the
      presence of joint purulent material, and/or bacterial pathogen isolation from
      joint fluid/synovial membrane/blood cultures and response to antibiotics. Data
      analysis was performed using SPSS 20. RESULTS: Patients had a mean age of 61.1 +/
      18.8 years, without sex predominance. 26.5 % had an infection <= 15 days before
      septic arthritis diagnosis. Besides previous infection, 57.4 % had >= 1 risk
      factors for septic arthritis, most commonly pharmacological immunosuppression
      (20.6 %), diabetes mellitus type 2 (19.1 %) and rheumatoid arthritis (17.6 %).
      The knee was the most often affected (54.3 %). Only 39.7 % presented fever from
      clinical onset until hospital admission (mean 13.4 +/- 18.9 days). Leucocytosis
      was present in 45.6 % of patients, elevated erythrocyte sedimentation rate (ESR)
      in 75 % and elevated C-reactive protein (CRP) in 97.1 %. 5.9 % had articular
      damage attributable to septic arthritis. An infectious agent was isolated in 41.2
      % of patients, with Staphylococcus aureus being the most frequent. 38.7 % of
      synovial fluid and 23.5 % of synovial membrane cultures were positive. Patients
      with an identified infectious agent have no significant differences other than
      more days of hospitalisation (p = 0.003) and in-hospital antibiotic treatment (p
      = 0.017). CONCLUSION: Synovial fluid and synovial membrane cultures more often
      identified pathogens compared to blood or urine cultures. Patients with and
      without an identified infectious agent have similar demographic, clinical,
      laboratory and radiographic characteristics.

PMID- 24318568
TI  - A systematic review on the safety and efficacy of yttrium-90 radioembolization
      for unresectable, chemorefractory colorectal cancer liver metastases.
AB  - INTRODUCTION: The management of unresectable, chemorefractory colorectal cancer
      liver metastases (CRCLM) is a clinical dilemma. Yttrium-90 (Y90)
      radioembolization is a potentially safe and effective treatment for patients with
      CRCLM who have failed conventional chemotherapy regimens. METHODS: A systematic
      review of clinical studies before November 2012 was performed to examine the
      radiological response, overall survival and progression-free survival of patients
      who underwent Y90 radioembolization of unresectable CRCLM refractory to systemic
      therapy. The secondary objectives were to evaluate the safety profile of this
      treatment and identify prognostic factors for overall survival. RESULTS: Twenty
      studies comprising 979 patients were examined. Patients had failed a median of 3
      lines of chemotherapy (range 2-5). After treatment, the average reported value of
      patients with complete radiological response, partial response and stable disease
      was 0% (range 0-6%), 31% (range 0-73%) and 40.5% (range 17-76%), respectively.
      The median time to intra-hepatic progression was 9 months (range 6-16). The
      median overall survival was 12 months (range 8.3-36). The overall acute toxicity
      rate ranged from 11 to 100% (median 40.5 %). Most cases of acute toxicity were
      mild (Grade I or II) (median 39%; range 7-100%) which resolved without
      intervention. The number of previous lines of chemotherapy (>= 3), poor
      radiological response to treatment, extra-hepatic disease and extensive liver
      disease (>= 25%) were the factors most commonly associated with poorer overall
      survival. CONCLUSION: Y90 radioembolization is a safe and effective treatment of
      CRCLM in the salvage setting and should be more widely utilized.

PMID- 24318569
TI  - Translating disability in a Muslim community: a case of modular translation.
AB  - This study examines how Muslim religious leaders (imams) introduce the liberal
      notion of disability to their communities in Israel. The project described,
      initiated and supported by an American NGO, provides a case for exploring how the
      secular notion of disability rights is cast and recast in a Muslim world of
      meaning. It focuses on the mediation strategy that I call modular translation,
      employed by imams in sermons delivered for the purpose of altering or improving
      the status and conditions of people with disabilities. This strategy, as it
      emerged from the analysis, entails decoupling norms of conduct from their
      underlying justifications. It thus suggests that norms of conduct are open to
      change so long as the believers' cosmology remains intact. As such, this turn may
      offer new avenues of thinking and acting about globalizing human rights within
      the arena of health and disability. 

PMID- 24318570
TI  - High aldehyde dehydrogenase activity identifies cancer stem cells in human
      cervical cancer.
AB  - High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of
      cells with cancer stem cell (CSC) properties in several malignancies. To clarify
      whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDH
      high and ALDH low cells were sorted from 4 cervical cancer cell lines and 5
      primary tumor xenografts and examined for CSC characteristics. Here, we
      demonstrate that cervical cancer cells with high ALDH activity fulfill the
      functional criteria for CSCs: (1) ALDH high cells, unlike ALDH low cells, are
      highly tumorigenic in vivo; (2) ALDH high cells can give rise to both ALDH high
      and ALDH low cells in vitro and in vivo, thereby establishing a cellular
      hierarchy; and (3) ALDH high cells have enhanced self-renewal and differentiation
      potentials. Additionally, ALDH high cervical cancer cells are more resistant to
      cisplatin treatment than ALDH low cells. Finally, expression of the stem cell
      self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is
      elevated in ALDH high cervical cancer cells. Taken together, our data indicated
      that high ALDH activity may represent both a functional marker for CCSCs and a
      target for novel cervical cancer therapies.

PMID- 24318571
TI  - Catalytically active telomerase holoenzyme is assembled in the dense fibrillar
      component of the nucleolus during S phase.
AB  - The maintenance of human telomeres requires the ribonucleoprotein enzyme
      telomerase, which is composed of telomerase reverse transcriptase (TERT),
      telomerase RNA component, and several additional proteins for assembly and
      activity. Telomere elongation by telomerase in human cancer cells involves
      multiple steps including telomerase RNA biogenesis, holoenzyme assembly,
      intranuclear trafficking, and telomerase recruitment to telomeres. Although
      telomerase has been shown to accumulate in Cajal bodies for association with
      telomeric chromatin, it is unclear where and how the assembly and trafficking of
      catalytically active telomerase is regulated in the context of nuclear
      architecture. Here, we show that the catalytically active holoenzyme is initially
      assembled in the dense fibrillar component of the nucleolus during S phase. The
      telomerase RNP is retained in nucleoli through the interaction of hTERT with
      nucleolin, a major nucleolar phosphoprotein. Upon association with TCAB1 in S
      phase, the telomerase RNP is transported from nucleoli to Cajal bodies,
      suggesting that TCAB1 acts as an S-phase-specific holoenzyme component.
      Furthermore, depletion of TCAB1 caused an increase in the amount of telomerase
      RNP associated with nucleolin. These results suggest that the TCAB1-dependent
      trafficking of telomerase to Cajal bodies occurs in a step separate from the
      holoenzyme assembly in nucleoli. Thus, we propose that the dense fibrillar
      component is the provider of active telomerase RNP for supporting the continued
      proliferation of cancer and stem cells. 

PMID- 24318572
TI  - An exploration of the self-advocacy support role through collaborative research:
      'there should never be a them and us'.
AB  - BACKGROUND: The role of the support worker in self-advocacy groups for people
      with intellectual disability is pivotal in setting the scene for empowerment.
      However, despite the growing importance of the role, it has attracted very little
      scrutiny. METHOD: The study developed an inclusive team approach working
      alongside researchers labelled with learning difficulties. Emphasis was placed on
      making all aspects of the research cycle accessible to the team. A variety of
      qualitative methods were used. RESULTS: Despite supporters' allegiances to
      disability equality and their emphasis on reflexivity, many crucial aspects of
      organizational practice and support remained hidden. However, an emerging shared
      narrative about the potential of people first implied the possibility of
      increased collaboration. This was evidenced in some of the groups. CONCLUSIONS:
      Where problematic practice was discussed, supporters were open to developing
      alternative approaches. Acknowledging members contributions alongside the work of
      their supporters helped nurture more collaborative relationships. A lot of
      accessible methods were used to find out what was happening. Much support work is
      hidden away and not listed by organisations. The supporter role is very complex
      where supporters are managed by members. Supporters may find ways to hold on to
      power even when they say they try not to. There were some good ways seen for
      members and supporters to work together fairly. The writer talks about working in
      a team with researchers with learning difficulties. The study concludes that we
      can all learn from each other.

PMID- 24318573
TI  - The influence of coronary calcium score on the interpretation of myocardial
      perfusion imaging.
AB  - PURPOSE: Coronary artery calcium (CAC) scores influence the pre-test likelihood
      of ischemia in patients undergoing myocardial perfusion imaging (MPI). We
      investigated the influence of CAC score knowledge on the visual interpretation of
      MPI in patients referred for the diagnostic work-up of suspected coronary artery
      disease. METHODS: We retrospectively analyzed symptomatic patients who were
      referred for MPI. For the current analysis, we selected 151 patients who
      underwent SPECT MPI with simultaneous CAC scoring. MPI was visually interpreted
      in two separate sessions, first without and then with knowledge of the CAC score.
      MPI results were classified into four groups: normal, fixed defects, ischemia,
      and equivocal. RESULTS: Mean age of the patients was 64 +/- 11 years, 56% were
      male. Without knowledge of the CAC score MPI was evaluated as normal in 36%,
      compared to 40% with knowledge of the CAC score (P = 0.636). Overall, the
      addition of the CAC score changed the interpretation of MPI in 56 patients (37%).
      Importantly, the frequency of equivocal MPI interpretations decreased from 21%
      without knowledge of CAC score to 9% with knowledge of CAC score (P = 0.002).
      CONCLUSIONS: Knowledge of the CAC score has a major impact on the interpretation
      of MPI, increasing the interpretative certainty.

PMID- 24318574
TI  - Identification and molecular characterization of a single-stranded circular DNA
      virus with similarities to Sclerotinia sclerotiorum hypovirulence-associated DNA
      virus 1.
AB  - A putative circular single-stranded DNA (ssDNA) virus was recovered from
      Hypericum japonicum collected in Vietnam. The viral isolate was tentatively named
      Hypericum japonicum-associated circular DNA virus (HJasCV). HJasCV shares 58.7
      65.4% nucleotide sequence identity with Sclerotinia sclerotiorum hypovirulence
      associated DNA virus 1 (SsHADV-1) and SsHADV-1-like viruses. Like this group of
      viruses, the genome of HJasCV (2 200 nt) has two large ORFs, one in the virion
      sense and the other in the complementary-sense DNA. The proteins encoded in the
      virion-sense and complementary-sense ORFs share 39-46 % and 45-67 % amino acid
      sequence identity with the putative capsid and replication-associated proteins
      (Reps), respectively, of SsHADV-1 and SsHADV-1-like viruses. The putative Rep of
      HJasCV contains all of the motifs related to rolling-circle replication. Its 111
      bp intergenic region (IR) contains a hairpin structure with a geminivirus-like
      nonanucleotide sequence, TAATGTTAT, at the apex of the loop. Phylogenetic
      analysis revealed that HJasCV forms a monophyletic clade with SsHADV-1 and SsHADV
      1-like viruses.

PMID- 24318575
TI  - Genetic variation analysis of apple chlorotic leaf spot virus coat protein
      reveals a new phylogenetic type and two recombinants in China.
AB  - In this study, we generated sequences of the apple chlorotic leaf spot virus
      (ACLSV) coat protein (CP) gene. Genetic variation and phylogenetic analyses were
      carried out on these sequences along with others reported previously. ACLSV
      populations clustered into four types: in three of the four types, combinations
      of three amino acids at positions of 40, 75 and 79 were conserved. The fourth
      phylogenetic type, newly identified here, was characterized by co-variation of
      Ser(40)-Tyr(75)-Ser(79). Statistically significant genetic differentiation and
      infrequent gene flow were detected among the four types. Two natural recombinants
      were detected for the first time among ACLSV isolates/genotypes from China. 

PMID- 24318577
TI  - Dealing with religious issues in counseling and psychotherapy: A symposium.

PMID- 24318576
TI  - Guidelines for health.

PMID- 24318578
TI  - Some contributions of christianity to psychotherapy.

PMID- 24318579
TI  - Priestcraft and psychoanalytic psychotherapy: Contradiction or concordance?

PMID- 24318580
TI  - Logotherapy as a bridge between religion and psychotherapy.

PMID- 24318582
TI  - Discussion: Psychology, inspiration, and faith.

PMID- 24318581
TI  - The world view factor in psychotherapy.

PMID- 24318583
TI  - Models of health and wholeness.
AB  - A church-clinic model of the neighborhood health center, developed initially in a
      low-income area, has now been established over the past three years in middle-
      and upper-income areas. The church-clinics, called Wholistic Health Centers, are
      primary care medical clinics located in church buildings that utilize an
      interdisciplinary team in the planning for patient treatment and health
      education. The project integrates primary medical care with pastoral counseling
      services. Evaluation of the two clinics in middle-to-upper-income areas indicates
      that the patients are middle to upper class, well educated, and are not medically
      disenfranchised; their presenting problems are only slightly more often medical
      (58%) than psychosocial (42%). 

PMID- 24318584
TI  - Anton Boisen revisited.
AB  - Anton Boisen was both a psychologist of religion and a schizophrenic. His
      autobiography presents his "case history" but leaves many of his psychotic
      communications and experiences uninterpreted. This essay attempts to account for
      Boisen's most idiosyncratic psychotic products, drawing on theories of Jung and
      Bateson. Boisen and Jung both used experiences deriving from psychotic episodes
      to shape their subsequent life work. Boisen remained within liberal
      Protestantism, relinquishing his own "crazy" critique of Christianity developed
      during his mental illness. This critique is expressed through Boisen's notion of
      the "Family of Four", a plan for world renewal that he himself never adequately
      interpreted. 

PMID- 24318585
TI  - Perspectives on contemporary mysticism.
AB  - Contemporary mysticism is in continuity with religious mysticism of all ages.
      Mysticism, like all religion, has an ideological and an experiential dimension.
      Traditional Freudian theory is inadequate for understanding either the
      ideological or the cognitive aspect, because it does not adequately account for
      either the cognitive process or the self-conscious "I." Categories of both ego
      psychology and the social scientific approach to religion illuminate contemporary
      mysticism in ways unavailable to the traditional Freudian psychoanalytic
      approach. The epistemological implications of the mystical attitude are
      considered, in both the religious and the scientific enterprises. 

PMID- 24318586
TI  - American values and contraceptive acceptance.
AB  - A number of individual personality factors and social norms may be associated
      with reproductive confusion and/or irresponsibility. More specifically, the
      values underlying common American social norms may contribute to ineffective
      birth planning in the following ways: 1) The traditional roles of women in our
      society seem to encourage parenthood. The rule has been early marriage, closely
      spaced children, and few alternate sources of satisfaction or self-esteem. 2) Our
      culture strongly encourages family life. Children are a symbol of normalcy. 3)
      The importance of sexual enjoyment per se often conflicts with contraceptive use.
      Conversely, innocence is also valued and also contributes to unprotected sexual
      activity. 4) Religious reasons or adherence to concepts of natural law are almost
      always given by people opposed to contraception. 5) Health is important to
      Americans, and birth control methods negatively affect health in real and
      imagined ways. Social norms, though changing, remain essentially congruent with
      former contraceptive technology and former ideologies, customs, and dreams. 

PMID- 24318587
TI  - Bile enhances cell surface hydrophobicity and biofilm formation of
      bifidobacteria.
AB  - Twenty-four human bifidobacterial strains were analysed for cell surface
      hydrophobicity (CSH) using a salt aggregation test (SAT) and a Congo red binding
      (CRB) assay. Three strains were selected for a systematic study on the CSH and
      biofilm formation: Bifidobacterium breve 46, Bifidobacterium animalis ssp. lactis
      8:8 and a reference strain B. animalis ssp. lactis JCM 10602. CRB of the B. breve
      46 and B. animalis ssp. lactis JCM 10602 was significantly enhanced (P < 0.05)
      when grown in deMan-Rogosa-Sharpe cysteine (MRSC) broth supplemented with
      taurocholic acid (TA) or native porcine bile (PB). An enhanced CSH of the strains
      grown with PB and gastric mucin correlated with an increased mucin binding and an
      enhanced biofilm formation in prebiotic oligosaccharide-supplemented cultures.
      The three strains showed late bile-induced biofilm (72 h) under an anaerobic
      growth condition, and both B. animalis ssp. lactis strains showed a late bile
      induced biofilm formation under aerobic conditions shown by crystal violet
      staining. These two strains were thus considered to be oxygen tolerant and more
      robust. Furthermore, enhanced biofilm formation of these robust bifidobacterial
      strains in the presence of prebiotics may allow for strong colonisation in the
      gastrointestinal tract when administered to in vivo models as a "synbiotic
      supplement".

PMID- 24318588
TI  - Functional analysis of the potential enzymes involved in sugar modulation in high
      and low sugarcane cultivars.
AB  - Sugarcane (Saccharum spp.) is a dynamic C4 polyploidy grass used as a major
      source of sucrose and an alternative for ethanol, food, and energy. Despite
      growing scientific interest, various sucrose metabolism regulatory aspects have
      been limited. Biochemical and gene expression studies were conducted on
      developmental stages, 240-420 days of planting (DAP) in mature leaves of three
      high and three low sucrose sugarcane cultivars. Sucrose synthase (SS) and sucrose
      phosphate synthase (SPS) activities were found to be remarkably higher at 240-360
      DAP but decrease at 420 DAP. Twofold increases of SS activity was estimated at
      240-360 DAP while SPS activity trend was found to be lower than the SS activity.
      In comparing SS and SPS activities with the brix of respective DAP, results show
      that these activities are significant and positively correlated with 'r' values
      of 0.69 and 0.68 for SS and SPS, respectively. However, the soluble acid
      invertase (SAI) and neutral invertase (NI) activities were found to decrease
      significantly with the maturity of cultivars, negatively correlating with brix at
      'r' values 0.83 and 0.89 for SAI and NI, respectively. The antioxidant enzyme
      activity was modulated similar to the invertases activity. Of the six genes, ESAS
      11 and 23 associated with sucrose accumulation and ESTS 34 and 41 associated with
      sugar transport in sugarcane were differentially expressed among the selected
      high and low sugarcane cultivars. Hence, these findings reinforce the selection
      of diverse sugarcane cultivars for gene expression studies targeting to
      quantitative traits and candidate marker determination.

PMID- 24318589
TI  - Development of a novel affinity membrane purification system for
      deoxyribonuclease.
AB  - A membrane based affinity purification system was developed for the purification
      of the DNA specific nuclease, DNase I. Single stranded DNA was bound to
      unmodified polyvinylidene fluoride (PVDF) membranes which were used to purify
      DNase I from a solution of bovine serum albumin. Using coated membranes, a 6-fold
      increase in specific activity was achieved with 80 % enzyme recovery. This method
      provides a simple yet effective way to purify DNase I and can be very useful for
      the purification of other DNA specific enzymes.

PMID- 24318590
TI  - Production and characterization of a milk-clotting protease produced in submerged
      fermentation by the thermophilic fungus Thermomucor indicae-seudaticae N31.
AB  - Proteases are some of the most important industrial enzymes, and one of their
      main applications is for the production of cheese in the dairy industry. Due to a
      shortage of animal rennet, microbial coagulant proteases are being sought. In
      this work, the production of microbial rennet from Thermomucor indicae-seudaticae
      N31 was studied in submerged fermentation. The best enzyme production was
      obtained in a fermentation medium containing 4 % wheat bran as the substrate in
      0.3 % saline solution, incubated for 72 h at 45  degrees C and 150 rpm. The value
      of the milk clotting activity (MCA) was 60.5 U/mL, and the ratio to proteolytic
      activity (MCA/PA) was 510. The crude enzyme showed optimum pH at 5.5 and two
      peaks of optimum temperature (MCA at 65  degrees C and PA at 60  degrees C). The
      MCA was stable in the pH range 4.0-4.5 for 24 h and up to 55  degrees C for 1 h.
      It was stable during storage at different temperatures (-20 to 25  degrees C) for
      10 weeks. Based on these results, we conclude that microbial rennet from T.
      indicae-seudaticae N31 produced by submerged fermentation showed good prospects
      of replacing traditional rennet.

PMID- 24318591
TI  - Metabolic engineering of Escherichia coli for production of 2-phenylethanol from
      renewable glucose.
AB  - 2-Phenylethanol (2-PE) is an important aromatic alcohol with a rose-like odor and
      has wide applications. The present work aims to construct a synthetic pathway for
      2-PE synthesis from glucose in Escherichia coli. First, the genes adh1 (encoding
      alcohol dehydrogenase) and kdc (encoding phenylpyruvate decarboxylase) from
      Saccharomyces cerevisiae S288c and Pichia pastoris GS115 were investigated in E.
      coli, respectively, and single overexpression of adh1 or kdc significantly
      increased 2-PE accumulation. When co-overexpressing adh1 and kdc, 2-PE was
      increased up to 130 from 57 mg/L. Furthermore, by optimizing coordinated
      expression of the four committed genes aroF, pheA, adh1 and kdc, 2-PE was
      improved to 285 mg/L which was the highest production of 2-PE by the recombinant
      E. coli system. In addition, our results also demonstrated that the tyrB gene,
      which encodes aromatic-amino-acid transaminase, plays an important role on 2-PE
      synthesis.

PMID- 24318592
TI  - Extramedullary T-lymphoid blast crisis of an ETV6/ABL1-positive
      myeloproliferative neoplasm with t(9;12)(q34;p13) and t(7;14)(p13;q11.2).

PMID- 24318593
TI  - Quality of life more impaired in younger than in older diffuse large B cell
      lymphoma survivors compared to a normative population: a study from the
      population-based PROFILES registry.
AB  - The objective of this study was to compare health-related quality of life (HRQOL)
      between diffuse large B cell lymphoma (DLBCL) survivors of different age
      categories (18-59/60-75/76-85 years) and to compare their HRQOL with an age- and
      sex-matched normative population. The population-based Eindhoven Cancer Registry
      was used to select all patients diagnosed with DLBCL from 1999 to 2010. Patients
      (n = 363) were invited to complete the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
      questionnaire, and 307 survivors responded (85 %). Data from an age- and sex
      matched normative population (n = 596) were used for comparison. DLBCL survivors
      aged 18-59 years scored better on physical functioning, quality of life, appetite
      loss and constipation than survivors of 76-85 years old (all p < 0.05). Financial
      problems more often occurred in survivors aged 18-59 years compared to survivors
      of 76-85 years old (p < 0.01). Compared to the normative population, DLBCL
      survivors aged 18-59 years showed worse scores on cognitive and social
      functioning and on dyspnea and financial problems (p < 0.01, large- and medium
      size effects). In survivors of the other age categories, only differences with
      trivial or small-size effects were found. Although younger DLBCL survivors have
      better HRQOL than older survivors, the differences found between younger
      survivors and normative population were the largest. This suggests that having
      DLBCL has a greater impact on younger than older survivors and that the worse
      HRQOL observed in older DLBCL survivors in comparison with younger survivors is
      caused mostly by age itself and not by the disease. 

PMID- 24318596
TI  - Multichemical resistance of the coniferPodocarpus gracilior (Podocarpaceae) to
      insect attack.
AB  - Podocarpus gracilior is resistant in nature to insect attack. Apparently, the
      resistance ofP. gracilior is due to a multichemical defense mechanism. Chemicals
      identified as potential components of the multichemical defense are four
      norditerpenedilactones, including nagilactones, C, D, and F, which cause insect
      feeding deterrent activity ultimately coupled to an insecticidal activity, and
      podolide, an insecticide; two nonlethal growth-inhibiting biflavones,
      podocarpusflavone A and 7",4'"-dimethylamentoflavone; and the ecdysis-inhibiting
      phytoecdysone, ponasterone A. 

PMID- 24318597
TI  - Volatile compounds from the predatory insectPodisus maculiventris (Hemiptera:
      Pentatomidae) : Male and female metathoracic scent gland and female dorsal
      abdominal gland secretions.
AB  - In the predatory spined soldier bug,Podisus maculiventris, the dorsal abdominal
      glands are much smaller in adult females than males. Females produce a mixture of
      (E)-2-hexenal, (E)-2-octenal, (E)-2-hexenoic acid, benzaldehyde, and nonanal in
      these glands. The female dorsal abdominal gland secretion may be a close-range
      pheromone since the dorsal abdominal gland secretion from males has been shown to
      be a long-range aggregation pheromone in this species. The metathoracic scent
      gland secretions of male and female spined soldier bugs are apparently identical,
      and similar to that of other pentatomids, except for the presence of the
      monoterpene alcohol, linalool. 

PMID- 24318598
TI  - Specificity of hermit crab attraction to gastropod predation sites.
AB  - Chemical cues are important to hermit crabs in location of shells. The type of
      gastropod flesh at a predation site (area where a gastropod is being consumed)
      influences species of crabs attracted to the site. Additionally, amount of flesh
      at a site is an important factor influencing relative size of the site
      attendants. Chemical information broadcast from natural predation sites appears
      highly specific and may serve to separate shell searching of various sizes and
      species of hermit crabs in time and space. 

PMID- 24318599
TI  - Single cell responses of the Douglas-fir beetle,Dendroctonus pseudotsugae hopkins
      (Coleoptera: Scolytidae), to pheromones and host odors.
AB  - Olfactory perception of pheromones and host odors byDendroctonus pseudotsugae
      males and females was investigated through single cell recordings. Responses of
      71 cells (35 cells in males; 36 cells in females) were recorded to 1 MUg of 10
      pheromones and three host terpenes. The olfactory cells were classified into four
      types based on sensitivity and specificity for the various odors: (1) 3,2-MCHone
      (3-methyl-2-cyclohexenone) cells; (2) 3,2-MCHol (3-methyl-2-cyclohexenol) cells;
      (3) frontalin cells; and (4) synergist cells. 3,2-MCHone and 3,2-MCHol cells in
      both males and females were the most sensitive and specific of all cells recorded
      with a threshold ca. 0.001-0.01 MUg on filter paper. Frontalin cells were less
      specialized than the two aforementioned cell types and had a somewhat higher
      threshold of ca. 0.01 MUg. A larger percentage of these three cell types were
      recorded in males than in females. The synergist cells had the highest threshold
      of all recorded cell types and were the least specific. Each of these cells was
      most responsive to eithercis-verbenol,trans-verbenol, 1,2-MCHol, verbenone, alpha
      pinene, or limonene; however, responses could be elicited by stimulation with
      other pheromones or host terpenes at higher dosages. Instances of inhibition of
      nerve impulse activity from spontaneously active cells were observed during 3,2
      MCHol and 3,2-MCHone stimulation, thus suggesting multifunctional effects for
      these compounds. The results help explain the role of chemicals in host
      selection, aggregation, and colonization behavior of the beetle and further
      elucidate hypotheses put forth in an earlier electroantennogram study. 

PMID- 24318600
TI  - Plant-determined variation in the cardenolide content, thin-layer chromatography
      profiles, and emetic potency of monarch butterflies,Danaus plexippus L. Reared on
      milkweed plants in California: 2.Asclepias speciosa.
AB  - The pattern of variation in gross cardenolide concentration of 111Asclepias
      speciosa plants collected in six different areas of California is a positively
      skewed distribution which ranges from 19 to 344 MUg of cardenolide per 0.1 g dry
      weight with a mean of 90 MUg per 0.1 g. Butterflies reared individually on these
      plants in their native habitats ranged from 41 to 547 MUg of cardenolide per 0.1
      g dry weight with a mean of 179 MUg. Total cardenolide per butterfly ranged from
      54 to 1279 MUg with a mean of 319 MUg. Differences in concentrations and total
      cardenolide contents in the butterflies from the six geographic areas appeared
      minor, and there were no differences between the males and the females, although
      the males did weigh significantly more than females. The uptake of cardenolide by
      the butterflies was found to be a logarithmic function of the plant
      concentration. This results in regulation: larvae which feed on low-concentration
      plants produce butterflies with increased cardenolide concentrations relative to
      those of the plants, and those which feed on high-concentration plants produce
      butterflies with decreased concentrations. No evidence was adduced that high
      concentrations of cardenolides in the plants affected the fitness of the
      butterflies. The mean emetic potencies of the powdered plant and butterfly
      material were 5.62 and 5.25 blue jay emetic dose fifty units per milligram of
      cardenolide and the number of ED50 units per butterfly ranged from 0.28 to 6.7
      with a mean of 1.67. Monarchs reared onA. speciosa, on average, are only about
      one tenth as emetic as those reared onA. eriocarpa. UnlikeA. eriocarpa which is
      limited to California,A. speciosa ranges from California to the Great Plains and
      is replaced eastwards byA. syriaca L. These two latter milkweed species appear to
      have a similar array of chemically identical cardenolides, and therefore both
      must produce butterflies of relatively low emetic potency to birds, with
      important ecological implications. About 80% of the lower emetic potency of
      monarchs reared on A. speciosa compared to those reared onA. eriocarpa appears
      attributable to the higher polarity of the cardenolides inA. speciosa. Thin-layer
      Chromatographie separation of the cardenolides in two different solvent systems
      showed that there are 23 cardenolides in theA. speciosa plants of which 20 are
      stored by the butterflies. There were no differences in the cardenolide spot
      patterns due either to geographic origin or the sex of the butterflies. As when
      reared onA. eriocarpa, the butterflies did not store the plant cardenolides withR
      f values greater than digitoxigenin. However, metabolic transformation of the
      cardenolides by the larvae appeared minor in comparison to when they were reared
      onA. eriocarpa. AlthoughA. eriocarpa andA. speciosa contain similar numbers of
      cardenolides and both contain desglucosyrioside, the cardenolides ofA. speciosa
      overall are more polar. ThusA. speciosa has no or only small amounts of the
      nonpolar labriformin and labriformidin, whereas both occur in high concentrations
      inA. eriocarpa. A. speciosa plants and butterflies also contain uzarigen,
      syriogenin, and possibly other polar cardenolides withR f values lower than
      digitoxin. The cardenolide concentration in the leaves is not only considerably
      less than inA. eriocarpa, but the latex has little to immeasurable cardenolide,
      whereas that ofA. eriocarpa has very high concentrations of several cardenolides.
      Quantitative analysis ofR f values of the cardenolide spots, their intensities,
      and their probabilities of occurrence in the chloroform-methanol-formamide TLC
      system produced a cardenolide fingerprint pattern very different from that
      previously established for monarchs reared onA. eriocarpa. This dispels recently
      published skepticism about the predictibility of chemical fingerprints based upon
      ingested secondary plant chemicals. 

PMID- 24318601
TI  - (Z,E)-alpha-farnesene: Major component of secretion from metathoracic scent gland
      of cotton seed bug,Oxycarenus hyalinipennis (Costa) (Heteroptera; Lygaeidae).
AB  - The isolation and identification of (Z,E)-alpha-farnesene[(3Z, 6E)-3,7,11
      trimethyldodeca-1,3,6,10-tetraene] (III) as the major component of the secretion
      from the metathoracic scent gland of the cotton seed bug,Oxycarenus
      hyalinipennis, is reported. The compound was identified by a combination of [1H]
      NMR, [(13)C] NMR, UV, and mass spectral data and by comparison with a synthetic
      sample, prepared by dehydration of (E)-nerolidol. (Z,E)-alpha-Farnesene (III) has
      been recorded previously in insects (ants and termites), but this is the first
      report of its occurrence in a member of the Heteroptera. (E)2-Octenyl acetate
      (XIII) and 2-octenal (XIV) were identified as minor components of the secretion.
      In addition, three minor monoterpenoid and two other sesquiterpenoid components
      were detected and tentatively identified. 

PMID- 24318602
TI  - Volatile compounds from ponerine ants in the genusMesoponera.
AB  - Volatile constituents have been characterized from two species of ponerine ants
      in the genusMesoponera. 2,5-Dimethyl-3-isopentyl-pyrazine has been identified
      from cephalic extracts ofM. castanea andM. castaneicolor, by gas chromatography
      mass spectrometry. Combined gasters and thoraces of both species are also
      characterized by the presence of nonanal, nonanoic acid, isovaleric acid,
      phenylacetic acid, and undecanal, as well as a series of aliphatic amines and
      amides.N-Isoamylnonylamine was a major constituent that was accompanied byN
      isoamylnonenylamine,N,N-diisoamylnonylamine,N-acetyl nonylamine,N-formyl
      isoamylnonylamine,N-isovaleroyl nonylamine, and several other secondary and
      tertiary amines. The possible significance of the amines and amides as
      idiosyncratic natural products ofMesoponera species is discussed. 

PMID- 24318603
TI  - Male wing-gland pheromone ofEphestia elutella.
AB  - Sex pheromone extracted from glands on the forewings of maleEphestia elutella
      (Hubner) elicits a stereotyped courtship response from conspecific females. A
      bioassay for this sex pheromone was developed based on this behavior. Maximum
      production and responsiveness for males and females, respectively, occurred in
      insects more than 24 hr old.E. elutella females were not responsive to extracts
      made fromE.figulilella Gregson,E. kuehniella Zeller,E. cautella (Walker),
      orPlodia interpunctella (Hubner) males. 

PMID- 24318604
TI  - Biosynthesis of sex pheromone components and glycerolipid precursors from sodium
      [1-(14)C]acetate in redbanded leafroller moth.
AB  - Sodium [1-(14)C]acetate in water-dimethyl sulfoxide (1?1) was applied topically
      to sex pheromone glands ofArgyrolaenia velutinana. Radiolabel was incorporated
      into the pheromone components (Z)-11-tetradecenyl acetate and (E)-11-tetradecenyl
      acetate, and also into triacylglycerols, diacylglycerols, ethanolamine
      phosphatides, and choline phosphatides. In the triacylglycerols, radiolabel
      appeared in (Z)-11-tetradecenoate, (E)-11-tetradecenoate, tetradecanoate,
      hexadecanoate, and octadecanoate. In the choline phosphatides, the same acyl
      moieties incorporated radiolabel but at lower levels. In the diacylglycerols and
      ethanolamine phosphatides, only the radiolabel in hexadecanoate and octadecanoate
      was above the limit of detection. At different times following application of
      sodium [1-(14)C]acetate, the relative proportions of labeled (Z)-11-tetradecenyl
      acetate and (E)-11-tetradecenyl acetate changed very little, but the relative
      proportions of labeled fatty acyl moieties in the triacylglycerols and choline
      phosphatides changed markedly. After 8 min, triacylglycerols had incorporated
      about equal amounts of radiolabel into (Z)-11-tetradecenoate, (E)-11
      tetradecenoate, and tetradecanoate. As the incubation time was increased,
      triacylglycerols accumulated proportionately more radiolabeled (E)-11
      tetradecenoate than (Z)-11-tetradecenoate, and accumulated proportionately less
      radiolabeled tetradecanoate. In the choline phosphatides, at all times of
      incubation the amount of radiolabel incorporated into (Z)-11-tetradecenoate was
      small but above the limit of detection, and the amounts of radiolabel in (E)-11
      tetradecenoate and tetradecanoate were smaller and often below the limit of
      detection. In both the triacylglycerols and the choline phosphatides, the
      relative proportion of radiolabeled hexadecanoate decreased with time, and that
      of octadecanoate increased. 

PMID- 24318605
TI  - Allelopathic potential of sorghum (Sorghum bicolor): Isolation of seed
      germination inhibitors.

PMID- 24318606
TI  - Defensive secretion of the pill millipedeGlomeris marginata. I. Fluid production
      and storage.

PMID- 24318607
TI  - Heliox for croup in children.
AB  - BACKGROUND: Croup is thought to be triggered by a viral infection and is
      characterised by respiratory distress due to upper airway inflammation and
      swelling of the subglottic mucosa in children. Mostly it is mild and transient
      and resolves with supportive care. In moderate to severe cases, treatment with
      corticosteroids and nebulised epinephrine (adrenaline) is required.
      Corticosteroids improve symptoms but it takes time for a full effect to be
      achieved. In the interim, the child is at risk of further deterioration. This may
      rarely result in respiratory failure necessitating emergency intubation and
      ventilation. Nebulised epinephrine may result in dose-related adverse effects
      including tachycardia, arrhythmias and hypertension and its benefit may be short
      lived. Helium-oxygen (heliox) inhalation has shown therapeutic benefit in initial
      treatment of acute respiratory syncytial virus (RSV) bronchiolitis and may
      prevent morbidity and mortality in ventilated neonates. Heliox has been used
      during emergency transport of children with severe croup and anecdotal evidence
      suggests that heliox relieves respiratory distress. OBJECTIVES: To examine the
      effect of heliox on relieving symptoms and signs of croup, as determined by a
      croup score (a tool for measuring the severity of croup).To examine the effect of
      croup on rates of admission or intubation (or both), through comparisons of
      heliox with placebo or any active intervention(s) in children with croup. SEARCH
      METHODS: We searched CENTRAL 2013, Issue 10, MEDLINE (1950 to October week 5,
      2013), EMBASE (1974 to November 2013), CINAHL (1982 to November 2013), Web of
      Science (1955 to November 2013) and LILACS (1982 to November 2013). In addition,
      we searched two clinical trials registries: the World Health Organization
      International Clinical Trials Registry Platform (WHO ICTRP) and
      clinicaltrials.gov (searched 12 November 2013). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) and quasi-RCTs comparing the effect of helium-oxygen
      mixtures with placebo or any active intervention(s) in children with croup. DATA
      COLLECTION AND ANALYSIS: Two review authors independently identified and assessed
      citations for inclusion. A third review author resolved disagreements. We
      assessed included trials for allocation concealment, blinding of intervention,
      completeness of outcome data, selective outcome reporting and other potential
      sources of bias. We reported mean differences for continuous data and odds ratios
      for dichotomous data. We descriptively reported data not suitable for statistical
      analysis. MAIN RESULTS: We included three RCTs with a total of 91 participants.
      One study compared heliox 70%/30% with 30% humidified oxygen administered for 20
      minutes in children with mild croup and found no statistically significant
      differences in the overall change in croup scores between heliox and the
      comparator. In another study, children with moderate to severe croup were
      administered intramuscular dexamethasone 0.6 mg/kg and either heliox 70%/30% with
      one to two doses of nebulised saline, or 100% oxygen with one to two doses of
      nebulised racaemic epinephrine for three hours. In this study, the heliox group's
      croup scores improved significantly more at all time points from 90 minutes
      onwards. However, overall there were no significant differences in croup scores
      between the groups after four hours using repeated measures analysis. In a third
      study, children with moderate croup all received one dose of oral dexamethasone
      0.3 mg/kg with heliox 70%/30% for 60 minutes in the intervention group and no
      treatment in the comparator. There was a statistically significant difference in
      croup scores at 60 minutes in favour of heliox but no significant difference
      after 120 minutes. It was not possible to pool outcomes because the included
      studies compared different interventions and reported different outcomes. No
      adverse events were reported. AUTHORS' CONCLUSIONS: There is some evidence to
      suggest a short-term benefit of heliox inhalation in children with moderate to
      severe croup who have been administered oral or intramuscular dexamethasone. In
      one study, the benefit appeared to be similar to a combination of 100% oxygen
      with nebulised epinephrine. In another study there was a slight change in croup
      scores between heliox and controls, with unclear clinical significance. In
      another study in mild croup, the benefit of humidified heliox was equivalent to
      that of 30% humidified oxygen, suggesting that heliox is not indicated in this
      group of patients provided that 30% oxygen is available. Adequately powered RCTs
      comparing heliox with standard treatments are needed to further assess the role
      of heliox in children with moderate to severe croup.

PMID- 24318608
TI  - Current health-related quality of life is lower in former Division I collegiate
      athletes than in non-collegiate athletes.
AB  - BACKGROUND: College athletes participate in physical activity that may increase
      chronic stress and injury and induce overtraining. However, there is little known
      about how previous injuries that have occurred during college may limit current
      physical activity and/or decrease their subsequent health-related quality of life
      (HRQoL). PURPOSE: To evaluate HRQoL in former United States National Collegiate
      Athletic Association Division I athletes and nonathletes with the Patient
      Reported Outcomes Measurement Information System (PROMIS) and a demographics
      questionnaire. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2.
      METHODS: The study sample was recruited through alumni databases at a large
      Midwestern university and consisted of 2 cohorts: (1) former Division I athletes
      and (2) nonathletes who participated in recreational activity, club sports, or
      intramurals while attending college. Participants answered a survey constructed
      with a web-based system. All individuals contacted were between the ages of 40
      and 65 years. Study participants responded to the questions on the PROMIS scales
      for sleep, anxiety, depression, fatigue, pain interference, physical function,
      and satisfaction with participation in social roles. The PROMIS was developed to
      fill the void of HRQoL being evaluated by multiple instruments. An additional
      questionnaire was constructed to record demographic and exercise information.
      RESULTS: Initially, 1280 former Division I athletes and nonathletes were
      contacted; 638 surveys were returned (49.8%). Surveys eligible for analyses
      (71.6%) were completed by 232 former Division I athletes (mean age +/- SD, 53.36
      +/- 7.11 years) and 225 nonathletes (mean age +/- SD, 53.60 +/- 6.79 years).
      Univariate analyses for the effect of group was significantly related to PROMIS
      scales for physical function, depression, fatigue, sleep disturbances, and pain
      interference (P < .05). The overall scores were significantly worse for the
      former Division I athletes than for the nonathletes on 5 of the 7 scales. In
      addition, the former Division I athletes reported significantly more limitations
      in daily activities and more major and chronic injuries than did the nonathlete
      controls. CONCLUSION: According to these data, former Division I athletes have
      decreased HRQoL compared with nonathletes. CLINICAL RELEVANCE: Sports encourage
      physical activity, which help promote a healthy lifestyle. Moderate activity and
      exercise should be encouraged. However, the demands of Division I athletics may
      result in injuries that linger into adulthood and possibly make participants
      incapable of staying active as they age, thereby lowering their HRQoL.

PMID- 24318609
TI  - Health-related quality of life after anterior cruciate ligament reconstruction: a
      systematic review.
AB  - BACKGROUND: Anterior cruciate ligament reconstructions (ACLRs) are frequently
      performed on young, active patients and can result in persistent knee symptoms
      and activity limitations that may affect health-related quality of life (HRQoL).
      To date, there has been no systematic review of HRQoL outcomes after ACLR.
      PURPOSE: The objectives of this study were to report HRQoL >=5 years after ACLR,
      compare HRQoL outcomes with available population norms, and describe factors that
      may affect HRQoL in this population. STUDY DESIGN: Systematic review. METHODS:
      All studies reporting HRQoL >=5 years after ACLR with hamstring or patellar
      tendon autografts were eligible for review. Common HRQoL outcomes were pooled
      using a random-effects meta-analysis and compared with published population
      norms. The Spearman rank correlation coefficient (rho) was used to identify
      variables associated with HRQoL outcomes. Where insufficient data were available,
      outcomes were reported descriptively. RESULTS: Fourteen studies were eligible for
      review, and HRQoL was reported for 2493 patients at a mean of 9 years (range, 5
      16 years) after ACLR. Pooling of knee-related quality of life outcomes (Knee
      injury and Osteoarthritis Outcome Score [KOOS]-QOL) found impairments after ACLR
      when compared with population norms. In comparison, studies using the Short Form
      36 (SF-36) reported similar or better HRQoL compared with normative data. The
      KOOS-QOL subscores correlated strongly with KOOS-sport/recreation (rho = .70, P =
      .04) and KOOS-pain (rho = .85, P = .003) subscores. Severe radiographic
      osteoarthritis, meniscal injuries sustained after surgery, and revision ACLR were
      associated with poorer HRQoL outcomes at a minimum 5-year follow-up. The negative
      influence of concomitant meniscal surgery on HRQoL became apparent more than 10
      years after ACLR. CONCLUSION: This review found that patients assessed using a
      knee-specific measure (KOOS-QOL) were more likely to report poorer HRQoL values,
      compared with population norms, than those assessed using a generic HRQoL measure
      (SF-36). Revision surgeries, meniscal injuries, and severe radiographic
      osteoarthritis were associated with poorer HRQoL outcomes after ACLR. However,
      these relationships should be interpreted with caution, as they were only
      investigated in a small number of studies. CLINICAL RELEVANCE: These results can
      be used by clinicians to educate patients about potential long-term outcomes
      after ACLR and to develop strategies for optimizing postoperative HRQoL.

PMID- 24318610
TI  - Repair integrity and functional outcome after arthroscopic conversion to a full
      thickness rotator cuff tear: articular- versus bursal-side partial tears.
AB  - BACKGROUND: A few studies have compared high-grade partial-thickness articular-
      and bursal-side rotator cuff tears postoperatively. PURPOSE: To compare the
      clinical and radiological outcomes of high-grade partial-thickness rotator cuff
      tears treated with arthroscopic conversion to full-thickness tears, followed by
      repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Forty-three
      consecutive shoulders with high-grade partial-thickness rotator cuff tears (20
      articular- and 23 bursal-side lesions) treated with arthroscopic conversion to
      full-thickness tears, followed by repair using the suture-bridge technique, were
      evaluated. The final functional evaluation was conducted at a mean of 35.53
      months (range, 24-54 months). Radiological outcomes were evaluated at a minimum
      of 1 year postoperatively. The following outcome measures were used in this
      study: the American Shoulder and Elbow Surgeons (ASES) score, the University of
      California, Los Angeles (UCLA) Shoulder Rating Scale, the Constant score, and
      range of motion. RESULTS: At the final follow-up, the mean ASES, UCLA, and
      Constant scores improved significantly to 91.80, 32.70, and 75.85, respectively,
      in the articular-side group (all P < .001). The mean ASES, UCLA, and Constant
      scores improved significantly to 90.80, 32.52, and 83.00, respectively, in the
      bursal-side group (all P < .001). The UCLA and ASES scores did not differ
      significantly between the 2 groups (P = .821 and .869, respectively), while the
      Constant scores did (P = .048). The retear rate was 0% in the articular-side
      group and 9.5% in the bursal-side group; this difference was not significant (P =
      .204). CONCLUSION: The arthroscopic repair of partial-thickness bursal-side tears
      resulted in comparable or superior postoperative functional outcomes compared
      with that of articular-side tears. However, the postoperative retear rate did not
      differ significantly between the 2 groups.

PMID- 24318611
TI  - Mini-open tenorrhaphy of acute Achilles tendon ruptures: medium-term follow-up of
      100 cases.
AB  - BACKGROUND: The high incidence of soft tissue complications related to open
      Achilles repair has driven enthusiasm for developing minimally invasive surgical
      procedures. The Dresden procedure, which reduces wound-healing issues and avoids
      sural nerve damage, has recently been published and shows good functional
      results. OBJECTIVE: To evaluate medium-term clinical results of procedures using
      the Dresden mini-open technique on acute Achilles tendon ruptures. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: A retrospective analysis was
      performed on 100 consecutive patients with a mean follow-up of 42.1 months. At
      follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) score, time to
      return to work and sports, subjective satisfaction, and complications were
      registered. An isokinetic test was performed on the first 21 patients of this
      series at 1 year postoperatively. RESULTS: The mean time to return to work was
      56.0 days, and the mean time to return to sports was 18.9 weeks. The mean AOFAS
      score was 97.7; 98% of patients were satisfied. No complications regarding soft
      tissues and sural nerve damage were reported. Two reruptures and 5 cases of deep
      venous thrombosis were observed. The isokinetic evaluation showed good recovery
      of the involved muscles. CONCLUSION: The excellent functional and satisfaction
      results, ease of the procedure, and avoidance of sural nerve damage make the mini
      open technique a very attractive alternative for acute, spontaneous Achilles
      tendon ruptures.

PMID- 24318612
TI  - Femoral tunnel enlargement after medial patellofemoral ligament reconstruction:
      prevalence, risk factors, and clinical effect.
AB  - BACKGROUND: In recent years, significantly more attention has been focused on the
      role of the medial patellofemoral ligament (MPFL) in patellar stability, and MPFL
      reconstruction has become a mainstay of surgical treatment of episodic patellar
      dislocations. Although previously described in detail after reconstruction of the
      anterior cruciate ligament, tunnel enlargement has not been investigated after
      MPFL reconstruction. HYPOTHESES: (1) Femoral tunnel enlargement occurs after MPFL
      reconstruction. (2) Patella alta, trochlear dysplasia, and tunnel malposition are
      risk factors for tunnel enlargement. (3) The presence of tunnel enlargement is
      not associated with recurrent dislocations or poorer patient-reported outcome
      scores after MPFL reconstruction. STUDY DESIGN: Case-control study; Level of
      evidence, 3. METHODS: Fifty-five of 59 knees treated for episodic patellar
      dislocations with MPFL reconstruction between 2005 and 2010 were evaluated at 1
      year postoperatively for the presence of tunnel enlargement on lateral
      radiographs. Tunnel enlargement was defined as a tunnel area greater than 2 times
      that of the original tunnel. Knees with tunnel enlargement at 1 year were
      compared with those without tunnel enlargement. Patients were assessed for
      recurrent subluxations or dislocations at a mean of 3 years postoperatively, and
      patient-reported outcome scores were assessed in a subset of patients at a mean
      of 3.7 years postoperatively. RESULTS: Tunnel enlargement was noted in 23 knees
      (41.8%). No differences in patient age or body mass index were noted between the
      2 groups. The mean patellar height was significantly higher in the enlarged
      tunnel group (P = .03). A higher prevalence of trochlear dysplasia or tunnel
      malposition was not demonstrated in the enlarged tunnel group. Patient-reported
      outcome scores and the risk of recurrent patellar instability were equal in the 2
      groups. CONCLUSION: Femoral tunnel enlargement after MPFL reconstruction is
      common, with patients with patella alta at an increased risk. The influence of
      tunnel malposition and trochlear dysplasia on this condition requires further
      research. Recurrent instability and patient-reported outcome scores are not
      affected by tunnel enlargement.

PMID- 24318613
TI  - Divergent determinants of 18F-NaF uptake and visible calcium deposition in large
      arteries: relationship with Framingham risk score.
AB  - To compare regional vascular distribution and biological determinants of visible
      calcium load, as assessed by computed tomography, as well as of molecular calcium
      deposition as assessed by (18)F-NaF positron emission tomography. Eighty
      oncologic patients undergoing (18)F-NaF PET/CT scan were included in the study.
      Cardiovascular-risk stratification was performed according to a simplified
      version of the Framingham model [including age, diabetes, smoking, systolic blood
      pressure and body mass index (BMI)]. Arterial (18)F-NaF uptake was measured by
      drawing regions of interest comprising the arteries on each slice of the
      transaxial PET/CT and normalized to blood (18)F-NaF activity to obtain the
      arterial target-to-background ratio (TBR). The degree of arterial calcification
      (AC) was measured using a software program providing Agatston-like scores.
      Differences in mean values and regression analysis were tested. Predictors of AC
      and TBR were evaluated by univariate and multivariate analysis. p value of 0.05
      was considered statistically significant. No correlation was documented between
      regional calcium load and regional TBR in any of the studied arterial segments.
      Visible calcium deposition was found to be dependent upon age while it was not
      influenced by all the remaining determinants of cardiovascular risk. By contrast,
      (18)F-NaF uptake was significantly correlated with all descriptors of
      cardiovascular risk, with the exception of BMI. Vascular (18)F-NaF uptake
      displays a different regional distribution, as well as different biological
      predictors, when compared to macroscopic AC. The tight dependency of tracer
      retention upon ongoing biological determinants of vascular damage suggests that
      this tool might provide an unexplored window on plaque pathophysiology. 

PMID- 24318615
TI  - Visible-light-responsive reversible photoacid based on a metastable carbanion.
AB  - A new photoacid that reversibly changes from a weak to a strong acid under
      visible light was designed and synthesized. Irradiation generated a metastable
      state with high C?H acidity due to high stability of a trifluoromethyl-phenyl
      tricyano-furan (CF3 PhTCF) carbanion. This long-lived metastable state allows a
      large proton concentration to be reversibly produced with moderate light
      intensity. Reversible pH change of about one unit was demonstrated by using a 0.1
      mM solution of the photoacid in 95 % ethanol. The quantum yield was calculated to
      be as high as 0.24. Kinetics of the reverse process can be fitted well to a
      second-order-rate equation with k=9.78*10(2)  M(-1)  s(-1) . Response to visible
      light, high quantum yield, good reversibility, large photoinduced proton
      concentration under moderate light intensity, and good compatibility with organic
      media make this photoacid a promising material for macroscopic control of proton
      transfer processes in organic systems. 

PMID- 24318614
TI  - Left atrial booster-pump function as a predictive parameter for new-onset
      postoperative atrial fibrillation in patients with severe aortic stenosis.
AB  - Postoperative atrial fibrillation (POAF) is associated with increased risk of
      embolic events and heart failure, but its associated factors remains unknown.
      Left atrial (LA) subclinical mechanical dysfunction caused by the acute stress of
      surgery may be clinically manifested as POAF. The purpose of our study was
      therefore to test the hypothesis that preoperative LA subclinical myocardial
      dysfunction is a potential predictor of development of POAF in patients with
      aortic stenosis (AS). We studied 27 patients with severe AS undergoing aortic
      valve replacement (AVR) with left ventricular (LV) ejection fraction of 63 +/- 11
      %. All patients were in sinus rhythm and had no history of atrial fibrillation
      (AF). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa)
      functions were determined as the averaged global LA speckle-tracking longitudinal
      strain rates from apical four- and two-chamber views. POAF, defined as any
      episode of AF within 30-day after AVR, was observed in 15 patients (56 %). There
      were no differences in clinical characteristics, LA and LV volumes, and global LV
      function between patients with and without POAF. Multivariate logistic regression
      analysis identified SR-LAa as the only independent predictor of POAF.
      Furthermore, SR-LAa >0.79 s(-1) predicted POAF with 60 % sensitivity, 92 %
      specificity, and area under the curve of 0.828 (p < 0.0001). Of the 15 patients
      with POAF, one developed paroxysmal AF during long-term follow-up. In
      conclusions, SR-LAa helped to detect subtle LA booster-pump dysfunction and was
      associated with new-onset POAF in patients with severe AS. These findings may be
      useful for risk stratification and management of such patients.

PMID- 24318616
TI  - End product feedback effects on photosynthetic electron transport.
AB  - The inhibition of photosynthetic electron transport when starch and sucrose
      synthesis limit the overall rate of photosynthesis was studied inPhaseolus
      vulgaris L. andXanthium strumarium L. The starch and sucrose limitation was
      established by reducing photorespiration by manipulation of the partial pressure
      of O2 and CO2. Chlorophylla fluorescence quenching, the redox state of
      Photosystem I (estimated by the redox status of NADP-dependent malate
      dehydrogenase), and the intermediates of the xanthophyll cycle were investigated.
      Non-photochemical fluorescence quenching increased, NADP-dependent malate
      dehydrogenase remained at 100% activity, and the amount of violaxanthin decreased
      when starch and sucrose synthesis limited photosynthesis. In addition, O2-induced
      feedback caused a decrease in photochemical quenching. These results are
      consistent with a downward regulation of photosynthetic electron transport during
      end product feedback on photosynthesis. When leaves were held in high CO2 for 4
      hours, the efficiency of Photosystem II was reduced when subsequently measured
      under low light. The results indicate that the quantum efficiency of open
      Photosystem II centers was reduced by the 4 hour treatment. We interpret the
      results to indicate that feedback from starch and sucrose synthesis on
      photosynthetic electron transport stimulates mechanisms for dissipating excess
      light energy but that these mechanisms do not completely protect leaves from long
      term inhibition of photosynthetic electron transport capacity. 

PMID- 24318617
TI  - Molecular cloning and expression of chloroplast NADP-malate dehydrogenase during
      Crassulacean acid metabolism induction by salt stress.
AB  - A full-length cDNA clone for NADP(+)-dependent malate dehydrogenase (NADP-MDH; EC
      1.1.1.82) from the facultative CAM plant,Mesembryanthemum crystallinum has been
      isolated and characterized. NADP-MDH is responsible for the reduction of
      oxaloacetate to malate in the chloroplasts of higher plants. The cDNA clone is
      1747 bp in size and contains a single open reading frame encoding a 441 amino
      acid long precursor polypeptide with a predicted molecular weight of 47 949. The
      predicted, mature NADP-MDH polypeptide sequence fromM. crystallinum shares 82.7%
      to 84% amino acid identity with other known higher plant sequences. Genomic
      Southern blot analysis ofM. crystallinum DNA indicates that MDH is encoded by a
      small gene family. Steady-state transcript levels for chloroplast NADP-MDH
      decrease transiently in the leaves after salt stress and then increase to levels
      greater than two-fold higher than in unstressed plants. Transcript levels in
      roots are extremely low and are unaffected by salt-stress treatment. In vitro
      transcription run-on experiments using isolated nuclei from leaf tissue confirm
      that the accumulation of NADP-MDH transcripts is, at least in part, the result of
      increased transcription of this gene during salt stress. The salt-stress-induced
      expression pattern of this enzyme suggests that it may participate in the CO2
      fixation pathway during CAM. 

PMID- 24318618
TI  - Modification of the thermoluminescence properties of Ca(2+) depleted Photosystem
      II membranes by the 23 kDa extrinsic polypeptide and by oligocarboxylic acids.
AB  - Photosystem II membranes were isolated from chloroplasts of pokeweed (Phytolacca
      americana) and rendered deficient in Ca(2+), an inorganic cofactor of
      photosynthetic water oxidation. The thermoluminescence properties of such
      membranes were found to depend on the Ca(2+)-depleting method used. This feature
      was analyzed with respect to the thermoluminescence emission that accompanied the
      recombination reaction between the reduced acceptor QA (-) and the oxidant of the
      S2 state. It was determined that the differences observed among various
      preparations of Ca(2+)-depleted membranes were attributable to the presence or
      absence of the extrinsic 23 kDa polypeptide on the membranes. The binding of this
      polypeptide to Ca(2+)-depleted membranes devoid of the 17 and 23 kDa extrinsic
      polypeptides caused the thermoluminescence to be emitted at a higher temperature
      due to a further stabilization of an already abnormally stable S2 state. Addition
      of the chelators EDTA or EGTA and of citrate brought about a similar response.
      The conditions required for the upshift of the emission temperature of
      thermoluminescence strongly resembled those identified by Boussac et al. (FEBS
      Lett. 277 (1990) 69-74) as responsible for modifying the EPR multiline signal
      from the S2 state of Ca(2+)-depleted PS II membranes. Consistent with the
      authors' interpretation of the reason for this modification, we conclude that the
      elevated emission temperature of the thermoluminescence emission reflects an
      abnormal ligand environment of the Mn-center in PS II that may be created by a
      direct ligation of the added agents to Mn. Evidence is also presented that the
      return to a normal S2 after an addition of Ca(2+) occurs via yet another
      condition of S2 which, in terms of its thermoluminescence properties, resembles
      that of Ca(2+)-depleted membranes before addition of modifying agents, but is not
      identical to it. 

PMID- 24318619
TI  - Functional characterisation of a purified homogeneous Photosystem II core complex
      with high oxygen evolution capacity from spinach.
AB  - The functional properties of a purified homogeneous spinach PS II-core complex
      with high oxygen evolution capacity (Haag et al. 1990a) were investigated in
      detail by measuring thermoluminescence and oscillation patterns of flash induced
      oxygen evolution and fluorescence quantum yield changes. The following results
      were obtained: a) Depending on the illumination conditions the PS II-core
      complexes exhibit several thermoluminescence bands corresponding to the A band, Q
      band and Zv band in PS II membrane fragments. The lifetime of the Q band (Tmax=10
      degrees C) was determined to be 8s at T=10 degrees C. No B band corresponding to
      S2QB (-) or S3QB (-) recombination could be detected. b) The flash induced
      transient fluorescence quantum yield changes exhibit a multiphasi relaxation
      kinetics shich reflect the reoxidation of Q A (-) . In control samples without
      exogenous acceptors this process is markedly slower than in PS II membrane
      fragments. The reaction becomes significantly retarded by addition of 10 MUM
      DCMU. After dark incubation in the presence of K3[Fe(CN)6 c) Excitation of dark
      adapted samples with a train of short saturating flashes gives rise to a typical
      pattern dominated by a high O2 yield due to the third flash and a highly damped
      period four oscillation. The decay of redox states S2 and S3 are dominated by
      short life times of 4.3 s and 1.5 s, respectively, at 20 degrees C. The results
      of the present study reveal that in purified homogeneous PS II-core complexes
      with high oxygen evolution isolated from higher plants by beta-dodecylmaltoside
      solubilization the thermodynamic properties and the kinetic parameters of the
      redox groups leading to electron transfer from water to QA are well preserved.
      The most obvious phenomenon is a severe modification of the QB binding site. The
      implications of this finding are discussed. 

PMID- 24318620
TI  - Redox regulation of enzymatic activity and proteolytic susceptibility of ribulose
      1,5-bisphosphate carboxylase/oxygenase fromEuglena gracilis.
AB  - The activity of ribulose-1,5-bisphosphate carboxylase/oxygenase fromEuglena
      gracilis decays steadily when exposed to agents that induce oxidative
      modification of cysteine residues (Cu(2+), benzofuroxan, disulfides, arsenite,
      oxidized ascorbate). Inactivation takes place with a concomitant loss of cysteine
      sulfhydryl groups and dimerization of large subunits of the enzyme. 40% activity
      loss induced by the vicinal thiol-reagent arsenite is caused by modification of a
      few neighbor residues while the almost complete inactivation achieved with
      disulfides is due to extensive oxidation leading to formation of mixed disulfides
      with critical cysteines of the protein. In most cases oxidative inactivation is
      also accompanied by an increased sensitivity to proteolysis by trypsin,
      chymotrypsin or proteinase K. Both enzymatic activity and resistance to
      proteolysis can be restored through treatment with several thiols (cysteamine,
      cysteine, dithiothreitol and, more slowly, reduced glutathione). Redox effectors
      which are thought to regulate the chloroplast activity (NADPH, ferredoxin and
      thioredoxin) do not reactivate the oxidized enzyme. When ribulose-1,5-bisphoshate
      carboxylase/oxygenase is incubated with cystamine/cysteamine mixtures having
      different disulfide/thiol ratio (r), inactivation takes place around r=1.5 while
      proteolytic sensitization occurs under more oxidative conditions (r=4). It is
      suggested that oxidative modification may happen in vivo under exceptional
      circumstances, such as senescence, bleaching or different kinds of stress,
      leading to enzyme inactivation and triggering the selective degradation of the
      carboxylase that has been repeatedly observed during these processes. 

PMID- 24318621
TI  - Linear models relating xanthophylls and lumen acidity to non-photochemical
      fluorescence quenching. Evidence that antheraxanthin explains zeaxanthin
      independent quenching.
AB  - Zeaxanthin has been correlated with high-energy non-photochemical fluorescence
      quenching but whether antheraxanthin, the intermediate in the pathway from
      violaxanthin to zeaxanthin, also relates to quenching is unknown. The
      relationships of zeaxanthin, antheraxanthin and DeltapH to fluorescence quenching
      were examined in chloroplasts ofPisum sativum L. cv. Oregon andLactuca sativa L.
      cv. Romaine. Data matrices as five levels of violaxanthin de-epoxidation against
      five levels of light-induced lumen-proton concentrations were obtained for both
      species. The matrices included high levels of antheraxanthin as well as lumen
      proton concentrations induced by subsaturating to saturation light levels.
      Analyses of the matrices by simple linear and multiple regression showed that
      quenching is predicted by models where the major independent variable is the
      product of lumen acidity and de-epoxidized xanthophylls, the latter as the sum of
      zeaxanthin and antheraxanthin. The interactions of lumen acidity and xanthophyll
      concentration are shown in three-dimensional plots of the best-fit multiple
      regression models. Antheraxanthin apparently contributes to quenching as
      effectively as zeaxanthin and explains quenching previously not accounted for by
      zeaxanthin. Hence, we propose that all high-energy dependent quenching is
      xanthophyll dependent. Quenching requires a threshold lumen pH that varies with
      xanthophyll composition. After the threshold, quenching is linear with lumen
      acidity or xanthophyll composition. 

PMID- 24318622
TI  - Picosecond Raman spectroscopy of the B830 LH2 complex ofChromatium purpuratum BN
      5500.
AB  - A setup for generating the Stokes Raman lines of benzene (556, 588 and 624 nm,
      ~50 ps) by the use of the second harmonic of a Nd: YLF regenerative amplifier
      system (527 nm, 70 ps, 1 kHz) has been built. This was then used to detect, for
      the first time, the picosecond Raman spectrum of a carotenoid bound to an
      isolated light-harvesting complex of a photosynthetic bacterium. The 527 and 588
      nm pulses have been used, respectively, for pumping and probing (delay ~0 ps) the
      S1 and T1 states of okenone which is bound to both the isolated B830 LH2 complex
      and the chromatophores fromChromatium purpuratum BN 5500. Comparison of the above
      spectra with the S1 and T1 Raman spectra of all-trans-okenone, free inn-hexane
      solution, shows that only the T1 state is detected with the LH2 complex, and that
      both the S1 and T1 states are detected with the chromatophores. The results
      indicate that in the chromatophores there are at least two types of S1
      carotenoids with different lifetimes, i.e., one in the LH2 complex which is too
      short-lived to be detected, most probably due to efficient energy transfer to
      bacteriochlorophyll, and the other in either the reaction center or the LH1
      complex which is long-lived enough to be pumped and probed by 50 ~ 70 ps pulses.
      The results also indicate that at least two of the actively light-harvesting
      carotenoid molecules are in close connection in the isolated LH2 complex since
      the T1 state is generated through singlet homofission within the short S1
      lifetime. 

PMID- 24318623
TI  - History of concepts of the comparative biochemistry of oxygenic and anoxygenic
      photosyntheses.
AB  - Experiments of Hans Molisch in 1907 demonstrated that purple bacteria do not
      evolve molecular oxygen during photosynthetic metabolism, and can use organic
      compounds as sources of cell carbon for anaerobic 'photoheterotrophic' growth.
      Molisch's conclusion that he discovered a new photosynthetic growth mode was not
      accepted for some 30 years because of the prevailing definition of photosynthesis
      as light-dependent conversion of carbon dioxide and inorganic reductants to cell
      materials. Meanwhile, during the decade of the 1930s, Cornelis van Niel
      formulated the 'comparative biochemical watercleavage hypothesis' of
      photosynthesis, which enjoyed great popularity for about 20 years. According to
      this concept, photolysis of water yielded 'H' and 'OH', the former acting as the
      hydrogen donor for CO2 reduction in all modes of photosynthesis. Oxygenic
      organisms were presumed to contain a unique biochemical system capable of
      converting 'OH' to water and O2. To explain the absence of O2 formation by purple
      and green photosynthetic bacteria, it was supposed that such organisms lacked the
      oxygen-forming system and, instead, 'OH' was disposed of by reduction with an
      inorganic H(e) donor (other than water) according to the general
      equation:[Formula: see text] where H2A is H2 or an inorganic sulfur
      compound.Critical tests of van Niel's hypothesis could not be devised, and his
      proposal was abandoned soon after the discovery of in vitro photophosphorylation
      by green plant chloroplasts and membranes of purple bacteria in 1954.
      Photophosphorylation was then viewed as one key common denominator of oxygenic
      and anoxygenic photosyntheses. From later research it became clear that light
      dependent phosphorylation of adenosine diphosphate was a consequence of
      photochemical charge separation and electron flow in reaction centers embedded in
      membranes of all photosynthetic organisms. The similarities, as well as the
      differences, in fine structure and function of reaction centers in anoxygenic and
      oxygenic organisms are now believed to reflect the course of evolution of
      oxygenic organisms from anoxygenic photosynthetic precursors. Thus, with the
      acquisition of new knowledge, concepts of the comparative biochemistry of
      photosynthetic processes have been radically altered during the past several
      decades. This paper describes highpoints of the history of these changes. 

PMID- 24318624
TI  - Can charge recombination as caused by pH-dependent donor-side limitation in PS 2
      account for high-energy-state quenching?
AB  - Schreiber and Neubauer (Photosynthesis Research 25: 279-293, 1990) have proposed
      a model which explains energy quenching by enhanced triplet formation as caused
      by charge recombination due to pH-dependent donor-side limitation. Quenching
      under these conditions is assumed to result from two mechanisms. Firstly, there
      is the withdrawal of excited states by charge recombination and formation of
      triplet states. Secondly, these triplet states can result in carotenoid triplets
      in the antenna which are supposed to quench excitons. Here, it is shown that
      quenching caused by both mechanisms can account for only about 25% of the
      experimentally observed energy quenching even under extremely favorable
      conditions. More likely, this number is less than 15%, as the contribution of the
      second step in the proposed triplet cycle is expected to be low as the life times
      of the carotenoid triplets are not long enough to cause the assumed quenching of
      excitons in the antenna. 

PMID- 24318625
TI  - Long-term results of debridement and primary repair of peroneal tendon tears.
AB  - BACKGROUND: Peroneal tendon tears are relatively common; however, there are few
      reports on the long-term success of operative treatment. The purpose of this
      study was to review the long-term clinical and patient-reported outcomes of a
      cohort of patients with peroneal tendon tears treated with debridement and
      primary repair. METHODS: Patients who underwent debridement and primary repair of
      tears of the peroneus longus and brevis from 1994 to 2008 were included in the
      study. A chart review was performed to determine patient demographics,
      postoperative complications, and return to sport. Clinical outcomes scores used
      to assess patients preoperatively and at most recent follow-up included a visual
      analog scale (VAS) for pain, the SF-12 Health Survey, and the Lower Extremity
      Functional Scale (LEFS) questionnaire. RESULTS: We identified 34 patients with a
      tear of one or both peroneal tendons treated operatively by a single surgeon.
      Eighteen patients participated in the follow-up survey with an average follow-up
      time of 6.5 years (range, 2-14 years). There was significant improvement in mean
      VAS pain scores at the time of final follow-up (P < .001) from a mean of 39
      (range, 0-80) preoperatively to a mean of 10 (range, 0-52) postoperatively. In
      addition, there was a significant increase in the LEFS score from a mean of 45
      (range, 23-70) preoperatively to a mean of 71 (range, 24-80) postoperatively (P <
      .001). Of the 18 patients who responded, 17 returned to full sporting activity
      without limitation. There were no reoperations or operative failures during this
      time interval. CONCLUSIONS: Our study found excellent long-term functional
      outcomes for patients with tears of the peroneal tendons treated with debridement
      and primary operative repair. Moreover, we observed that the majority of patients
      returned to their previous level of activity without the need for reoperation or
      revision of the repair. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 24318626
TI  - Morbidity and complications following percutaneous calcaneal autograft bone
      harvest.
AB  - BACKGROUND: Autogenous bone grafting is commonly used as an adjuvant in foot and
      ankle procedures. The iliac crest and tibia are common sources of autogenous bone
      graft but require a separate operative site and have been reported to have
      significant morbidity including pain, fractures, and prolonged hospitalization.
      Bone grafting from the posterolateral calcaneus offers advantages such as a
      single operative field, ability to be done under an ankle block, and a
      theoretical low complication rate. We report our morbidity and complications of
      percutaneous calcaneal autograft bone harvest in patients undergoing foot
      operations. METHODS: Between 2006 and 2010, 6 foot and ankle surgeons performed a
      calcaneal bone graft on 393 patients undergoing foot procedures. Outcomes were
      measured through the use of a 4-question survey evaluating pain, subjective
      sensitivity at the incision site, numbness at the incision site, and limitation
      of shoe wear at a minimum of 1 year following the operation. Patient records were
      also examined for any additional complications that may have been reported.
      RESULTS: Of the 393 patients eligible for this study, 210 patients responded at
      an average of 2.8 years (range, 1.2-5.8 years) after the operation (minimum 1
      year). Of those, 181 patients (86.2%) reported no problems. Minor complications
      included 6 patients (2.9%) who experienced only incisional nerve sensitivity, 4
      patients (1.9%) with only incisional pain, 4 patients (1.9%) who reported some
      degree of incisional numbness only, 2 patients (1.0%) who reported only shoe wear
      limitations, and 10 patients (4.8%) who had a combination of symptoms. Three
      patients (1.4%) had more significant complications, which consisted of a
      pathological fracture through the graft site, a calcaneal stress fracture, and 1
      patient with permanent numbness along the distribution of the sural nerve.
      CONCLUSION: Calcaneal bone graft was an easily accessible source of local
      autogenous bone graft for foot and ankle procedures. Despite the simplicity of
      the procedure, minor complications are not infrequent, with 13.8% of patients
      reporting some residual symptoms along the lateral border of the calcaneus when
      bone graft was obtained through an oblique incision. LEVEL OF EVIDENCE: Level IV,
      case series.

PMID- 24318627
TI  - Surface water mineralization of isopyrazam according to OECD 309: observations on
      implementation of the new data requirement within agrochemical regulation.
AB  - A surface water mineralization study (according to the Organisation for Economic
      Co-operation and Development [OECD] guideline OECD 309) is a new requirement in
      European Union agrochemical regulations; therefore, industry has little
      experience with this test. The guideline allows for a number of options within
      the test design, notably the options to conduct the study under diffuse light and
      to include an inoculum of suspended sediment. The present study was designed to
      investigate the potential impact of these options on the degradation rate of a
      representative compound. The fungicide, isopyrazam, was chosen as it was
      previously shown to be susceptible to metabolism by phototrophic organisms under
      a fluorescent light-dark cycle. The impact of diffuse light was investigated at
      light intensities representative of those at depth in large, open water bodies
      (<7% of the incident intensity), and it was demonstrated that metabolism of
      isopyrazam by phototrophic microorganisms was rapid (median degradation time for
      50% of the test compound [DT50] < 50 d), whereas degradation in continuous
      darkness was negligible. Furthermore, investigation at 2 different light
      intensities resulted in similar degradation rates, indicating that this
      transformation mechanism was not proportional to light intensity, provided that
      there was sufficient light for photosynthesis to occur. Inclusion of suspended
      sediment did not have a significant impact on the degradation rate of isopyrazam,
      except at extremely high sediment concentrations, which were not considered
      representative of conditions in large, open water bodies.

PMID- 24318629
TI  - Myocardial necrosis depth prediction during extracellular photosensitization
      reaction of talaporfin sodium by defined index using fluorescence measurement.
AB  - An application of photodynamic therapy for myocardial ablation, which would
      induce myocardial electrical conduction block, is proposed. For the proposed
      application, an extracellular photosensitization reaction (PR) is performed while
      photosensitizer is distributed in myocardial interstitial space by employing a
      short drug-light interval. Because the myocardial necrosis depth must be
      accurately controlled to prevent surrounding tissue injury during the myocardial
      ablation procedure, the necrosis depth during PR needs to be predicted. The
      purpose of this study is to investigate the availability of predicting PR-induced
      myocardial necrosis depth (d(nec)) using a defined fluorescence-fall amount (FA),
      which is the calculated result of fluorescence intensity decrease from the start
      of the PR multiplied by irradiation duration and corresponds to photosensitizer
      consumption amount under an assumption that the photosensitizer consumption rate
      is faster than the photosensitizer supply rate. The correlation between FA and d
      nec was experimentally investigated in vivo using an open-chested canine heart
      model with 2.5 and 5.0 mg/kg of talaporfin sodium at an irradiance of 5-20
      W/cm(2) for 5-20 s. The fluorescence measurement was performed at a wavelength of
      710 nm during the PR to derive FA. One week after the PR, a uniform necrosis
      depth was measured histopathologically as d(mnec). A logarithmic correlation
      between d(mnec) and FA was confirmed with R(2) = 0.69-0.80 and a d(mnec) range of
      0.2-7.1 mm. The defined FA might be useful for predicting d nec for the
      extracellular PR in myocardium when using talaporfin sodium.

PMID- 24318628
TI  - Intense and specialized dendritic localization of the fragile X mental
      retardation protein in binaural brainstem neurons: a comparative study in the
      alligator, chicken, gerbil, and human.
AB  - Neuronal dendrites are structurally and functionally dynamic in response to
      changes in afferent activity. The fragile X mental retardation protein (FMRP) is
      an mRNA binding protein that regulates activity-dependent protein synthesis and
      morphological dynamics of dendrites. Loss and abnormal expression of FMRP occur
      in fragile X syndrome (FXS) and some forms of autism spectrum disorders. To
      provide further understanding of how FMRP signaling regulates dendritic dynamics,
      we examined dendritic expression and localization of FMRP in the reptilian and
      avian nucleus laminaris (NL) and its mammalian analogue, the medial superior
      olive (MSO), in rodents and humans. NL/MSO neurons are specialized for temporal
      processing of low-frequency sounds for binaural hearing, which is impaired in
      FXS. Protein BLAST analyses first demonstrate that the FMRP amino acid sequences
      in the alligator and chicken are highly similar to human FMRP with identical mRNA
      binding and phosphorylation sites, suggesting that FMRP functions similarly
      across vertebrates. Immunocytochemistry further reveals that NL/MSO neurons have
      very high levels of dendritic FMRP in low-frequency hearing vertebrates including
      alligator, chicken, gerbil, and human. Remarkably, dendritic FMRP in NL/MSO
      neurons often accumulates at branch points and enlarged distal tips, loci known
      to be critical for branch-specific dendritic arbor dynamics. These observations
      support an important role for FMRP in regulating dendritic properties of binaural
      neurons that are essential for low-frequency sound localization and auditory
      scene segregation, and support the relevance of studying this regulation in
      nonhuman vertebrates that use low frequencies in order to further understand
      human auditory processing disorders.

PMID- 24318630
TI  - Association between serum uric acid and lumbar spine bone mineral density in peri
      and postmenopausal Japanese women.
AB  - SUMMARY: Previous studies on the association between uric acid and bone mineral
      density yielded conflicting results. In this study, we demonstrated positive
      association between uric acid and lumbar spine bone mineral density in peri- and
      postmenopausal Japanese women. Further research is needed to elucidate the
      underlying mechanism. INTRODUCTION: Oxidative stress has been implicated in the
      pathogenesis of osteoporosis. Uric acid, a potent antioxidant substance, has been
      associated with bone mineral density but previous studies have yielded
      conflicting results. The objective of the study was to examine the association
      between serum uric acid and lumbar spine bone mineral density (BMD). METHODS:
      This was a retrospective analysis of medical records of 615 women, aged 45-75
      years, who had lumbar spine BMD measurement by dual-energy X-ray absorptiometry
      as a part of health checkup from August 2011 to July 2012. RESULTS: Mean serum
      uric acid level was 4.7 mg/dL. Serum uric acid level was positively and
      significantly associated with lumbar spine BMD independent of age, body mass
      index, smoking, drinking, physical activity, years after menopause, diabetes
      mellitus, hypertension, serum calcium, estimated glomerular filtration rate,
      plasma C-reactive protein, and serum alkaline phosphatase (standardized beta =
      0.078, p = 0.049). Uric acid rapidly increased until the age of 60 years, and
      then decelerated but continued to increase thereafter. The association between
      lumbar spine BMD and uric acid remained significantly positive after excluding
      women older than 60 years. CONCLUSION: The present study showed that higher uric
      acid levels were linearly associated with higher lumbar spine BMD in peri- and
      postmenopausal Japanese women. Further research is needed to elucidate the
      underlying mechanism of the association between uric acid and BMD.

PMID- 24318636
TI  - Spatial organization of cell-adhesive ligands for advanced cell culture.
AB  - Interaction between biomaterials and cells is a critical aspect for successful
      application of tissue engineering research. Technological advances within the
      past decade have enabled a number of studies to investigate how the spatial
      organization of cell-adhesive ligands impacts complex and rich cell behaviors
      ranging from adhesion to differentiation. Cells in their native environment are
      surrounded by chemical and physical factors spanning a range of length scales
      from nanometers to hundreds of microns. Furthermore, signals in the form of cell
      adhesive ligands presented from this environment in different size scales and/or
      geometrical arrangements can change how a cell senses and responds to its
      surroundings. Biology can thus convey information not only in the concentration
      of a ligand but through its ability to change the spatial organization of these
      cues, raising questions both on the mechanisms by which it patterns such
      information and on the means by which a cell interprets it. This review discusses
      major findings associated with various systems developed to study cell-adhesive
      ligand presentation as well as an overview of the important material systems used
      in these studies. Promising material systems to further investigations in this
      field are also examined. Future directions will likely include determining how
      cells sense local and global ligand concentrations, understanding underlying
      mechanisms that regulate cell behaviors, and investigating the function of more
      complex cell types and diverse ligands. 

PMID- 24318638
TI  - Transcriptional regulation improves the throughput of three-hybrid counter
      selections in Saccharomyces cerevisiae.
AB  - The yeast three-hybrid (Y3H) assay expands the fields of drug discovery and
      protein engineering by enabling the search of large variant libraries for targets
      that do not inherently produce a distinct, measurable phenotype. The Y3H assay
      links the DNA-binding and activation domains of a transcription factor via a
      chemically synthesized heterodimeric small molecule, thereby activating a
      downstream reporter gene. Although the Y3H assay has been successfully applied as
      a positive selection to discover novel drug targets and to evolve proteins with
      improved functions, its expansion into applications requiring a high-throughput,
      versatile selection against transcriptional activation has been hindered by its
      limited dynamic range as a counter selection. Here, we describe the development
      of a second-generation Y3H counter selection that uses the dual tetracycline
      (Tet) system to tighten transcriptional regulation of the reporter gene. The Tet
      Y3H counter selection has an improved dynamic range and provides enrichment from
      mock libraries of up to 106, a 104-fold improvement over our original Y3H counter
      selection. This enhanced dynamic range brings the Y3H counter selection to a
      standard that is suitable for real-world protein engineering applications.

PMID- 24318637
TI  - Molecular modeling of ErbB4/HER4 kinase in the context of the HER4 signaling
      network helps rationalize the effects of clinically identified HER4 somatic
      mutations on the cell phenotype.
AB  - In the ErbB/HER family of receptor tyrosine kinases, the deregulation of the
      EGFR/ErbB1/HER1, HER2/ErbB2, and HER3/ErbB3 kinases is associated with several
      cancers, while the HER4/ErbB4 kinase has been shown to play an anti-carcinogenic
      role in certain tumors. We present molecular and network models of HER4/ErbB4
      activation and signaling in order to elucidate molecular mechanisms of activation
      and rationalize the effects of the clinically identified HER4 somatic mutants.
      Our molecular-scale simulations identify the important role played by the
      interactions within the juxtamembrane region during the activation process. Our
      results also support the hypothesis that the HER4 mutants may heterodimerize but
      not activate, resulting in blockage of the HER4-STAT5 differentiation pathway, in
      favor of the proliferative PI3K/AKT pathway. Translating our molecular simulation
      results into a cellular pathway model of wild type versus mutant HER4 signaling,
      we are able to recapitulate the major features of the PI3K/AKT and JAK/STAT
      activation downstream of HER4. Our model predicts that the signaling downstream
      of the wild type HER4 is enriched for the JAK-STAT pathway, whereas downstream of
      the mutant HER4 is enriched for the PI3K/AKT pathway. HER4 mutations may hence
      constitute a cellular shift from a program of differentiation to that of
      proliferation. 

PMID- 24318642
TI  - Social vulnerability in paediatric dentistry: an overview of ethical
      considerations of therapeutic patient education.
AB  - Dental caries is a multifactorial condition that remains a major public health
      issue in high income countries. The prevalence of dental caries in children has
      markedly declined in most countries over the past 30 years. However, the disease
      continues to affect a vulnerable population defined as a high-risk group. As many
      public health policies are inefficient in dealing with this underprivileged
      group, it is necessary to find other strategies to decrease the incidence and the
      burden of dental caries. Defining dental caries as a chronic disease enables us
      to develop the concept of 'therapeutic patient education.' It is meant to train
      patients to self-manage or adapt treatment to their particular chronic disease
      and to cope with new processes and skills. The purpose of this paper is to
      propose a new approach to dental caries, in particular to early childhood caries.
      That should decrease the gravity and prevalence of the disease in this specific
      population. As a result, this new approach could increase the quality of life of
      many children both in terms of function and aesthetics.

PMID- 24318643
TI  - Percussion, diuresis, and inversion therapy for the passage of lower pole kidney
      stones following shock wave lithotripsy.
AB  - BACKGROUND: Lower pole kidney stones typically have poor rates of spontaneous
      clearance from the body. Some studies have suggested that diuresis, percussion
      and inversion therapy could be beneficial for people with lower pole kidney
      stones following shock wave lithotripsy. There is however controversy about the
      relative benefits, harms, and efficacy of these interventions for the management
      of lower pole kidney stones. OBJECTIVES: To identify the benefits and harms of
      percussion, diuresis, and inversion therapy to facilitate the passage of lower
      pole kidney stones following shock wave lithotripsy. SEARCH METHODS: We searched
      the Cochrane Renal Group's specialised register up to 27 November 2013 through
      contact with the Trials' Search Co-ordinator using search terms relevant to this
      review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi
      RCTs looking at the benefits and harms of percussion, diuresis, and inversion
      therapy for aiding passage of lower pole kidney stones following shock wave
      lithotripsy were sought for assessment. The first phases of randomised cross-over
      studies were also eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed study quality and extracted data. Results were
      expressed as relative risk (RR) for dichotomous outcomes and mean difference (MD)
      or standardised mean difference (SMD) for continuous data with 95% confidence
      intervals (CI). MAIN RESULTS: We identified two small studies (177 participants)
      for inclusion and analysis. One study (69 participants) compared percussion,
      diuresis and inversion therapy following shock wave lithotripsy versus
      observation-only after shock wave lithotripsy. This study reported significantly
      higher stone-free rates in the intervention group (RR 0.62, 95% CI 0.47 to 0.82)
      and a significant reduction in stone burden (MD -3.30, 95% CI -3.58 to -3.03)
      compared to the observation-only group. They reported no significant differences
      in complication rates (RR 3.00, 95% CI 0.12 to 76.24).The second study (108
      participants) compared percussion, diuresis, and inversion therapy plus shock
      wave lithotripsy with shock wave lithotripsy therapy alone. This study reported
      significantly higher stone-free rates in the intervention group (RR 0.36, 95% CI
      0.17 to 0.80) and a significant reduction in stone burden (MD -0.30, 95% CI -0.04
      to -0.56) compared to the control group. They reported no significant differences
      in complication rates (RR 2.54, 95% CI 0.10 to 63.72).For both studies selection
      bias was unclear; there was high risk of bias for performance bias; and
      detection, attrition and reporting bias were low. AUTHORS' CONCLUSIONS: Limited
      evidence from two small studies indicated that percussion, diuresis, and
      inversion therapy may be safe and effective therapies to assist clearance of
      lower pole kidney stone fragments following shock wave lithotripsy.
      Methodological quality in both studies was assessed as moderate. Further well
      designed and adequately powered studies are required to inform clinical practice.

PMID- 24318644
TI  - Do patients with juvenile idiopathic arthritis in remission exhibit active
      synovitis on joint ultrasound?
AB  - The aim of the study was to assess the presence and characteristics of
      subclinical synovitis using power Doppler (PD) ultrasonography on patients with
      juvenile idiopathic arthritis (JIA) in clinical remission and compare the
      findings with those of healthy children. A cross-sectional study was carried out
      involving the clinical (physical exam, functional capacity and laboratory tests)
      and ultrasonography evaluation of 34 joints (synovial fluid/hypertrophy, PD
      signal and bone erosion). Subclinical synovitis was defined as the presence of
      synovial hypertrophy/joint effusion with or without any PD signal. Thirty-six
      patients (11.5 +/- 3.74 years) and 36 controls (sex and age matched) were
      evaluated (2,448 joints). Twenty-seven patients were in remission on medication
      (mean duration: 1.8 +/- 2.2 years). Subclinical synovitis was detected in 41.7%
      patients and 11.1% controls (p = 0.003). Erosion was detected in three patients
      (8.3%). Subclinical synovitis was found in 38/1,224 (3.1%) joints in the patients
      (most affected: radiocarpal wrist, anterior elbow and tibiotalar ankle) and
      8/1,224 (0.6%) joints in the controls (most affected: radiocarpal wrist).
      Differences in subclinical synovitis between patients and controls were found in
      the elbows (p = 0.033) and ankles (p = 0.006). A greater frequency of subclinical
      synovitis was found in patients with the extended oligoarticular or polyarticular
      subtypes (p = 0.013), those at an older age at disease onset (p = 0.007) and
      using methotrexate (p = 0.049). Patients with JIA in remission exhibit
      subclinical synovitis more frequently than controls. Subclinical synovitis was
      more frequent in patients with the polyarticular involvement and those at an
      older age at disease onset.

PMID- 24318646
TI  - Cytotoxic effects of acrylamide in nerve growth factor or fibroblast growth
      factor 1-induced neurite outgrowth in PC12 cells.
AB  - Acrylamide is a neurological and reproductive toxicant in humans and laboratory
      animals; however, the neuron developmental toxicity of acrylamide remains
      unclear. The aims of this study are to investigate the cytotoxicity and neurite
      outgrowth inhibition of acrylamide in nerve growth factor (NGF)- or fibroblast
      growth factor 1 (FGF1)-mediated neural development of PC12 cells. MTS assay
      showed that acrylamide treatment suppresses NGF- or FGF1-induced PC12 cell
      proliferation in a time- and dose-dependent manner. Quantification of neurite
      outgrowth demonstrated that 0.5 mM acrylamide treatment resulted in significant
      decrease in differentiation of NGF- or FGF1-stimulated PC12 cells. This decrease
      is accompanied with the reduced expression of growth-associated protein-43, a
      neuronal marker. Moreover, relative levels of pERK, pAKT, pSTAT3 and pCREB were
      increased within 5-10 min when PC12 cells were treated with NGF or FGF1.
      Acrylamide (0.5 mM) decreases the NGF-induced activation of AKT-CREB but not ERK
      STAT3 within 20 min. Similarly, acrylamide (0.5 mM) decreases the FGF1-induced
      activation of AKT-CREB within 20 min. In contrast to the NGF treatment, the ERK
      STAT3 activation that was induced by FGF1 was slightly reduced by 0.5 mM
      acrylamide. We further showed that PI3K inhibitor (LY294002), but not MEK
      inhibitor (U0126), could synergize with acrylamide (0.5 mM) to reduce the cell
      viability and neurite outgrowth in NGF- or FGF1-stimulated PC12 cells. Moreover,
      acrylamide (0.5 mM) increased reactive oxygen species (ROS) activities in NGF- or
      FGF1-stimulated PC12 cells. This increase was reversed by Trolox (an ROS
      scavenging agent) co-treatment. Together, our findings reveal that NGF- or FGF1
      stimulation of the neuronal differentiation of PC12 cells is attenuated by
      acrylamide through the inhibition of PI3K-AKT-CREB signaling, along with the
      production of ROS.

PMID- 24318645
TI  - Biodegradable gold nanovesicles with an ultrastrong plasmonic coupling effect for
      photoacoustic imaging and photothermal therapy.
AB  - The hierarchical assembly of gold nanoparticles (GNPs) allows the localized
      surface plasmon resonance peaks to be engineered to the near-infrared (NIR)
      region for enhanced photothermal therapy (PTT). Herein we report a novel
      theranostic platform based on biodegradable plasmonic gold nanovesicles for
      photoacoustic (PA) imaging and PTT. The disulfide bond at the terminus of a PEG-b
      PCL block-copolymer graft enables dense packing of GNPs during the assembly
      process and induces ultrastrong plasmonic coupling between adjacent GNPs. The
      strong NIR absorption induced by plasmon coupling and very high photothermal
      conversion efficiency (eta=37%) enable simultaneous thermal/PA imaging and
      enhanced PTT efficacy with improved clearance of the dissociated particles after
      the completion of PTT. The assembly of various nanocrystals with tailored
      optical, magnetic, and electronic properties into vesicle architectures opens new
      possibilities for the construction of multifunctional biodegradable platforms for
      biomedical applications.

PMID- 24318647
TI  - Suppression of lipopolysaccharide-stimulated cytokine/chemokine production in
      skin cells by sandalwood oils and purified alpha-santalol and beta-santalol.
AB  - Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory
      properties; however, mechanism(s) for this activity have not been elucidated. To
      examine how SOs affect inflammation, cytokine antibody arrays and enzyme-linked
      immunosorbent assays were used to assess changes in production of cytokines and
      chemokines by co-cultured human dermal fibroblasts and neo-epidermal
      keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and
      East Indian sandalwood trees or to the primary SO components, alpha-santalol and
      beta-santalol. Lipopolysaccharides stimulated the release of 26 cytokines and
      chemokines, 20 of which were substantially suppressed by simultaneous exposure to
      either of the two sandalwood essential oils and to ibuprofen. The increased
      activity of East Indian SO correlated with increased santalol concentrations.
      Purified alpha-santalol and beta-santalol equivalently suppressed production of
      five indicator cytokines/chemokines at concentrations proportional to the
      santalol concentrations of the oils. Purified alpha-santalol and beta-santalol
      also suppressed lipopolysaccharide-induced production of the arachidonic acid
      metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co-cultures.
      The ability of SOs to mimic ibuprofen non-steroidal antiinflammatory drugs that
      act by inhibiting cyclooxygenases suggests a possible mechanism for the observed
      antiinflammatory properties of topically applied SOs and provides a rationale for
      use in products requiring antiinflammatory effects.

PMID- 24318648
TI  - Calibration of forcefields for molecular simulation: sequential design of
      computer experiments for building cost-efficient kriging metamodels.
AB  - We present a global strategy for molecular simulation forcefield optimization,
      using recent advances in Efficient Global Optimization algorithms. During the
      course of the optimization process, probabilistic kriging metamodels are used,
      that predict molecular simulation results for a given set of forcefield parameter
      values. This enables a thorough investigation of parameter space, and a global
      search for the minimum of a score function by properly integrating relevant
      uncertainty sources. Additional information about the forcefield parameters are
      obtained that are inaccessible with standard optimization strategies. In
      particular, uncertainty on the optimal forcefield parameters can be estimated,
      and transferred to simulation predictions. This global optimization strategy is
      benchmarked on the TIP4P water model.

PMID- 24318649
TI  - Hamiltonian replica-exchange simulations with adaptive biasing of peptide
      backbone and side chain dihedral angles.
AB  - A Hamiltonian Replica-Exchange Molecular Dynamics (REMD) simulation method has
      been developed that employs a two-dimensional backbone and one-dimensional side
      chain biasing potential specifically to promote conformational transitions in
      peptides. To exploit the replica framework optimally, the level of the biasing
      potential in each replica was appropriately adapted during the simulations. This
      resulted in both high exchange rates between neighboring replicas and improved
      occupancy/flow of all conformers in each replica. The performance of the approach
      was tested on several peptide and protein systems and compared with regular MD
      simulations and previous REMD studies. Improved sampling of relevant
      conformational states was observed for unrestrained protein and peptide folding
      simulations as well as for refinement of a loop structure with restricted
      mobility of loop flanking protein regions.

PMID- 24318650
TI  - Study of Cl(-)(H2O)n (n = 1-4) using basin-hopping method coupled with density
      functional theory.
AB  - Cl(-)(H2O)n (n = 1-4) clusters were investigated using a basin-hopping (BH)
      algorithm coupled with density functional theory (DFT). Structures, energetics,
      thermodynamics, vertical detachment energies, and vibrational frequencies were
      obtained from high-level ab initio calculations. Through comparisons with
      previous theoretical and experimental data, it was demonstrated that the
      combination of the BH method and DFT could accurately predict the global and
      local minima of Cl(-)(H2O)n (n = 1-4). Additionally, to optimize larger Cl(
      )(H2O)n (n > 4) clusters, several popular density functionals as well as DF-LMP2
      (Schutz et al., J. Chem. Phys. 2004, 121, 737) (second-order Moller-Plesset
      perturbation theory using local and density fitting approximations) were tested
      with appropriate basis sets through comparisons with MP2 optimized results. DF
      LMP2 will be used in future studies because its overall performance in describing
      the relative binding energies and the geometrical parameters of Cl(-)(H2O)n (n =
      1-4) was outstanding in this study.

PMID- 24318653
TI  - MYC and MiR: vicious circle.

PMID- 24318654
TI  - Sleep quality and fatigue after a stress management intervention for women with
      early-stage breast cancer in southern Florida.
AB  - BACKGROUND: Sleep disruption and fatigue are ubiquitous among cancer patients and
      are sources of stress that may compromise treatment outcomes. Previously, we
      showed that a cognitive behavioral stress management (CBSM) intervention reduced
      anxiety and other stress-related processes in women undergoing primary treatment
      for breast cancer. PURPOSE: This study examined secondary outcomes from a CBSM
      intervention trial for women with early-stage breast cancer to test if CBSM would
      improve sleep quality and fatigue among these patients at a single site in
      southern Florida. CBSM-related effects have already been demonstrated for
      indicators of psychosocial adaptation (e.g., general and cancer-related anxiety).
      METHODS: Patients were randomized to CBSM (n= 120) or a 1-day psychoeducation
      control group (n= 120). The Pittsburgh Sleep Quality Index (PSQI) and Fatigue
      Symptom Inventory were completed prior to randomization and 6 and 12 months after
      the baseline assignment. RESULTS: In latent growth analyses, women in CBSM
      reported greater improvements in PSQI sleep quality scores than controls,
      although there were no significant differences between conditions on PSQI total
      scores. Women in CBSM also reported greater reductions in fatigue-related daytime
      interference than controls, though there were no significant differences in
      changes in fatigue intensity. Changes in sleep quality were associated with
      changes in fatigue. CONCLUSIONS: Future work may consider integrating sleep and
      fatigue content into stress management interventions for women with early-stage
      breast cancer.

PMID- 24318655
TI  - Blood pressure regulation V: in vivo mechanical properties of precapillary
      vessels as affected by long-term pressure loading and unloading.
AB  - Recent studies are reviewed, concerning the in vivo wall stiffness of arteries
      and arterioles in healthy humans, and how these properties adapt to iterative
      increments or sustained reductions in local intravascular pressure. A novel
      technique was used, by which arterial and arteriolar stiffness was determined as
      changes in arterial diameter and flow, respectively, during graded increments in
      distending pressure in the blood vessels of an arm or a leg. Pressure-induced
      increases in diameter and flow were smaller in the lower leg than in the arm,
      indicating greater stiffness in the arteries/arterioles of the leg. A 5-week
      period of intermittent intravascular pressure elevations in one arm reduced
      pressure distension and pressure-induced flow in the brachial artery by about
      50%. Conversely, prolonged reduction of arterial/arteriolar pressure in the lower
      body by 5 weeks of sustained horizontal bedrest, induced threefold increases of
      the pressure-distension and pressure-flow responses in a tibial artery. Thus, the
      wall stiffness of arteries and arterioles are plastic properties that readily
      adapt to changes in the prevailing local intravascular pressure. The discussion
      concerns mechanisms underlying changes in local arterial/arteriolar stiffness as
      well as whether stiffness is altered by changes in myogenic tone and/or wall
      structure. As regards implications, regulation of local arterial/arteriolar
      stiffness may facilitate control of arterial pressure in erect posture and
      conditions of exaggerated intravascular pressure gradients. That increased
      intravascular pressure leads to increased arteriolar wall stiffness also supports
      the notion that local pressure loading may constitute a prime mover in the
      development of vascular changes in hypertension.

PMID- 24318657
TI  - Cult and culture.

PMID- 24318658
TI  - Reflections on death.

PMID- 24318656
TI  - Neck cooling and cognitive performance following exercise-induced hyperthermia.
AB  - PURPOSE: To assess the efficacy of neck cooling on cognitive performance
      following exertional hyperthermia. METHODS: Twelve healthy men completed two
      experimental trials [control (CON) and neck cooling collar (NCC)] in a counter
      balanced design. They ran on a treadmill at 70% VO2peak under warm and humid
      conditions (dry bulb temperature: 30.2 +/- 0.3  degrees C, relative humidity: 71
      +/- 2 %) for 75 min or until volitional exhaustion. Gastrointestinal, neck and
      skin temperatures, heart rate and subjective ratings were assessed. Serum brain
      derived neurotrophic factor (BDNF) levels were measured before and after each
      run. Cognitive performance comprising symbol digit matching, search and memory,
      digit span, choice reaction time and psychomotor vigilance test (PVT) were
      assessed before and after exercise. RESULTS: Mean gastrointestinal temperature
      was similar after exercise between trials (CON: 39.5 +/- 0.4  degrees C vs. NCC:
      39.6 +/- 0.3  degrees C; p = 0.15). Mean neck temperature was lowered in NCC
      compared to CON after the run (36.4 +/- 1.6  degrees C vs. NCC: 26.0 +/- 0.3 
      degrees C; p < 0.001). Exercise-induced hyperthermia improved mean reaction time
      in the symbol digit matching test (-134 +/- 154 ms; p < 0.05) and the PVT (-18 +/
      30 ms; p < 0.05). Maximum span was increased in the digit span test (1 +/- 2; p
      < 0.05). Application of NCC reduced the number of search errors made in level 3
      of the search and memory test (p < 0.05). Mean serum BDNF levels were increased
      following exercise-induced hyperthermia in both trials (p < 0.05). CONCLUSION:
      Exercise-induced hyperthermia improves working memory and alertness. Neck cooling
      may only enhance performance in tasks of higher complexity.

PMID- 24318659
TI  - Suffering and faith.
AB  - It is hypothesized that, under the impact of suffering or loss, some Christians
      not only grieve for what has been lost but also experience feelings of separation
      from their God and mourn that loss also. This "spiritual mourning" may take
      different forms and may lead to different outcomes in ways more or less analogous
      to those described for mourning and variants thereof by various workers. Drawing
      upon such work, the author describes certain possible forms of "spiritual
      mourning." 

PMID- 24318660
TI  - Adolescent sexuality and love.
AB  - Adolescent love in its approach to human sexuality emphasizes freedom, to the
      exclusion of responsibility. Less than twenty percent of the adolescent couples
      who engage in sexual relations use any type of contraception, and three-quarters
      of all pregnancies occur prior to marriage. Further, children born out of wedlock
      from such unions suffer frequently from social, economic, health, and educational
      handicaps. In addition, there are the problems of increasing abortions and
      venereal disease for the young parents, along with child abuse and a suicide rate
      among teenage mothers ten times that of the general population. Four possible
      ways to aid in the solution of these problems are suggested. 

PMID- 24318661
TI  - Buber's interpersonal theory as a hermeneutic.
AB  - Martin Buber is remembered as a philosopher, existentialist, Zionist, and Jewish
      theologian. The purpose of this article is to demonstrate that his theory of
      interpersonal relations forms a useful tool for categorizing some of the
      theoretical perspectives and therapeutic techniques within psychiatry. It is
      neither the intention nor purpose of the authors to judge the relative merits of
      competing modalities of treatment but to clarify their therapeutic mechanisms in
      such a way as to identify their purposes more precisely. Additionally, the
      authors wish to categorize the various schools of psychotherapy and their
      subdivisions according to the realm in which they are operative. Finally, they
      hope to demonstrate that Buber's system can be modified or elaborated upon by
      this connection with some of these approaches to personality theory. 

PMID- 24318662
TI  - Ethnic culture, religion, and the mental health of Slavic-American women.
AB  - Findings of a comparative research study of women of different ethnic back
      grounds suggest that the Slavic religioethnic culture acts to promote successful
      aging and stable mental health among women of Slavic heritage. Home and family
      structure, deep religiosity, and participation in church and community affiars
      provide function and meaningful purpose to life that tends to mitigate the losses
      inherent in the aging process. 

PMID- 24318663
TI  - Religion, personality, and clinical assessment.
AB  - Religion is an integral part of every person's life and occupies a central place
      in every personality. Viewing "religion" as referring to that which is of primary
      importance in one's life, one sees it as performing an integrative function,
      consolidating and ordering all of the "inputs" to personality, and giving
      consistency to one's behavior. Thus, an understanding of the individual and an
      assessment of his religion are necessary for a complete understanding of his
      problems. 

PMID- 24318664
TI  - Schreber'sMemoirs: Myth or personal lamentation.
AB  - Lucy Bregman's approach to Schreber'sMemoirs is scrutinized and found to be based
      on a number of fallacious and contradictory assumptions that call her
      interpretation of the book as personal religious myth into question. A social
      constructionist approach to mythology maintained by Berger and Luckmann is
      advanced, suggesting that at best Schreber's work qualifies as a quasi-mythical
      attempt to explain the source of his personal sociopsychic suffering. The family
      and interpersonal dynamics of Schreber's quasi-myth are investigated.
      Similarities to other cases of psychotic quasi-myths are noted and a general
      relationship between oppressive socialization and psychotic communications is
      advanced, as well as a specific alternative interpretation of Schreber's work to
      that proposed by Bregman. 

PMID- 24318665
TI  - Religious images in dreams.
AB  - In the tradition of Jung's analytical psychology, specimen dreams are given to
      illustrate: 1) traditional religious images modified by the personal context; 2)
      dreams in which material appears that has traditional religious meaning, but not
      in the conscious religious tradition of the dreamer ("archetypal images" in
      dreams); and 3) dreams that seem to carry a numinous religious meaning, but have
      not been shown to use traditional religious images. An understanding of the
      possible religious meaning of dreams should be a specialized but necessary aspect
      of counseling in depth, whether done by secular professionals or by pastoral
      counselors identified with traditional collective religious organizations. 

PMID- 24318666
TI  - Sex differences in opisthorchiosis and the development of cholangiocarcinoma in
      Syrian hamster model.
AB  - Worldwide, the highest incidence of cholangiocarcinoma (CCA) is found in
      northeast Thailand, the endemic area of Opisthorchis viverrini infection.
      Cumulated clinical data revealed that the majority of CCA patients are men.
      However, many other types of cancers are more commonly found in women. In this
      study, we investigated the sex differences in the development of CCA, induced by
      O. viverrini infection and N-nitrosodimethylamine administration, in Syrian
      hamsters. Histopathology, liver function tests, and fecal egg counts were
      analyzed. The results showed that there are no sex differences in hamsters
      responses to O. viverrini infection and no prevalence of CCA development. Even
      though serum ALT level in O. viverrini-infected or CCA hamsters was significantly
      increased in female compared to male (p < 0.05) and uninfected control (p <
      0.05), our results may imply that the higher prevalence of opisthorchiasis and
      CCA in men than in women in northeast Thailand may depend on behaviors of an
      individual exposed to risk factors rather than gender difference.

PMID- 24318668
TI  - Authors' response to Das R and Neumann P. Re: Resnick NM, Perera S, Tadic S,
      Organist L, Riley MA, Schaefer W, Griffiths D. What predicts and what mediates
      response of urge urinary incontinence to biofeedback? Neurourol Urodyn. 2013
      Jun;32(5):408-15.

PMID- 24318667
TI  - The RNA binding protein RBPMS is a selective marker of ganglion cells in the
      mammalian retina.
AB  - There are few neurochemical markers that reliably identify retinal ganglion cells
      (RGCs), which are a heterogeneous population of cells that integrate and transmit
      the visual signal from the retina to the central visual nuclei. We have developed
      and characterized a new set of affinity-purified guinea pig and rabbit antibodies
      against RNA-binding protein with multiple splicing (RBPMS). On western blots
      these antibodies recognize a single band at ~24 kDa, corresponding to RBPMS, and
      they strongly label RGC and displaced RGC (dRGC) somata in mouse, rat, guinea
      pig, rabbit, and monkey retina. RBPMS-immunoreactive cells and RGCs identified by
      other techniques have a similar range of somal diameters and areas. The density
      of RBPMS cells in mouse and rat retina is comparable to earlier semiquantitative
      estimates of RGCs. RBPMS is mainly expressed in medium and large DAPI-, DRAQ5-,
      NeuroTrace- and NeuN-stained cells in the ganglion cell layer (GCL), and RBPMS is
      not expressed in syntaxin (HPC-1)-immunoreactive cells in the inner nuclear layer
      (INL) and GCL, consistent with their identity as RGCs, and not displaced amacrine
      cells. In mouse and rat retina, most RBPMS cells are lost following optic nerve
      crush or transection at 3 weeks, and all Brn3a-, SMI-32-, and melanopsin
      immunoreactive RGCs also express RBPMS immunoreactivity. RBPMS immunoreactivity
      is localized to cyan fluorescent protein (CFP)-fluorescent RGCs in the B6.Cg
      Tg(Thy1-CFP)23Jrs/J mouse line. These findings show that antibodies against RBPMS
      are robust reagents that exclusively identify RGCs and dRGCs in multiple
      mammalian species, and they will be especially useful for quantification of RGCs.

PMID- 24318669
TI  - Emerging targets in migraine.
AB  - Migraine is a common and highly disabling neurological disorder. Despite the
      complexity of its pathophysiology, substantial advances have been achieved over
      the past 20 years in its understanding, as well as the development of
      pharmacological treatment options. The development of serotonin 5-HT(1B/1D)
      receptor agonists ("triptans") substantially improved the acute treatment of
      migraine attacks. However, many migraineurs do not respond satisfactorily to
      triptans and cardiovascular co-morbidities limit their use in a significant
      number of patients. As migraine is increasingly considered to be a disorder of
      the brain, and preclinical and clinical data indicate that the observed
      vasodilation is merely an epiphenomenon, research has recently focused on the
      development of neurally acting compounds that lack vasoconstrictor properties.
      This review highlights the most important pharmacological targets for which
      compounds have been developed that are highly likely to enter or have already
      advanced into clinical trials for the acute and preventive treatment of migraine.
      In this context, preclinical and clinical data on compounds acting on calcitonin
      gene-related peptide or its receptor, the 5-HT(1F) receptor, nitric oxide
      synthase, and acid-sensing ion channel blockers are discussed.

PMID- 24318670
TI  - Stratified phase II trial to establish the usefulness of the collagen gel droplet
      embedded culture-drug sensitivity test (CD-DST) for advanced gastric cancer.
AB  - BACKGROUND: We conducted a multicenter phase II trial to assess the suitability
      of three types of chemotherapy (docetaxel plus S-1, irinotecan plus S-1, or S-1
      alone) for patients with advanced gastric cancer by means of the collagen gel
      droplet embedded culture-drug sensitivity test (CD-DST). To our knowledge, this
      is the first multicenter clinical trial that has employed CD-DST to choose
      anticancer agents for the treatment of advanced gastric cancer. METHODS: Subjects
      (n = 64) were patients with advanced or recurrent gastric cancer. Patients were
      allocated to one of the treatment regimens on the basis of CD-DST results.
      Outcome of the patients was compared between the groups deemed chemosensitive or
      chemoresistant by the CD-DST. RESULTS: Thirty-three patients showed high
      sensitivity (T/C ratio <60 %) to at least one type of anticancer agent (sensitive
      group), and 31 showed low sensitivity (T/C ratio >=60 %) to all agents (resistant
      group). Specifically, the 1-year survival rate was significantly higher in the
      sensitive group (78.5 %; 95 % CI, 67.2-94.7 %) than in the resistant group (54.7
      %; 95 % CI, 38.7-74.3 %; P = 0.019), whereas time to progression (TTP) was
      significantly longer in the sensitive group (59.8 %; 95 % CI, 48.2-81.7 %) than
      in the resistant group (30.0 %; 95 % CI 13.6-46.4 %; P = 0.023). Median survival
      time was also significantly longer in the sensitive group (15.5 months; 95 % CI,
      12.8-18.2) than in the resistant group (12.5 months; 95 % CI, 10.2-14.9; P =
      0.038). CONCLUSIONS: CD-DST predicts the outcome of patients undergoing
      chemotherapy for advanced gastric cancer, presumably through evaluating
      chemosensitivity.

PMID- 24318671
TI  - Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic
      gastric cancer.
AB  - BACKGROUND: The incorporation of docetaxel into the cisplatin and fluorouracil
      backbone has been demonstrated to be an active combination in metastatic gastric
      cancer. Nevertheless, this regimen is burdened by nonnegligible toxicity. We
      hypothesized that replacing cisplatin and fluorouracil with oxaliplatin and
      capecitabine should be an active and safe option for metastatic gastric cancer
      patients. METHODS: In this phase II study, we tested the activity of docetaxel in
      combination with oxaliplatin and capecitabine (DOC) as a first-line treatment.
      DOC was administered as follows: docetaxel (60 mg/m(2)) and oxaliplatin (100
      mg/m(2)) on day 1, and capecitabine (500 mg/m(2)) was administered orally twice
      daily given continuously, with cycles repeated every 3 weeks. The primary
      endpoint was the overall response rate. RESULTS: Forty-eight patients entered the
      study. All patients had metastatic disease (stage IV). None of the patients had
      previously received chemotherapy for advanced disease. Performance status was 0,
      1, and 2 in 25, 58, and 17 % of patients, respectively; 13 patients (27 %) had
      adenocarcinoma of the gastroesophageal junction, and 29 patients (60.5 %) had two
      or more metastatic sites. The overall response rate was 52.1 %. Progression-free
      survival and overall survival were 6.9 and 12.6 months, respectively. The
      treatment was well tolerated with no treatment-related deaths. The most common
      grade 3-4 toxicity was neutropenia (41 %). CONCLUSIONS: DOC is an effective and
      tolerated first-line treatment, and the lower dose of docetaxel and oxaliplatin
      used in this study compared with other similar regimens does not seem to hamper
      the antitumor activity.

PMID- 24318672
TI  - Validation of the Portuguese version of the Brief Multidimensional Measure of
      Religiousness/Spirituality (BMMRS-P) in clinical and non-clinical samples.
AB  - Despite Brazil's high levels of religious involvement, there is a scarcity of
      validated religiousness/spirituality (R/S) measures in Portuguese, particularly
      multidimensional ones. This study presents the validation of the Portuguese
      version of the "Brief Multidimensional Measure in Religiousness and Spirituality"
      (BMMRS) within the Brazilian context. Inpatients (262) and caregivers (389) at
      two hospitals of Brazil answered the BMMRS, the DUREL-p, and a sociodemographic
      questionnaire. The internal and convergent validity and test-retest reliability
      for major dimensions were good. Discriminant validity was high (except for the
      Forgiveness dimension). The Portuguese version of the BMMRS is a reliable and
      valid instrument to assess multiple R/S dimensions in clinical and non-clinical
      samples. 

PMID- 24318673
TI  - Salinity induced the changes of root growth and antioxidative responses in two
      wheat cultivars.
AB  - This study aimed to investigate the inhibitory mechanism of root growth and to
      compare antioxidative responses in two wheat cultivars, drought-tolerant Ningchun
      and drought-sensitive Xihan, exposed to different NaCl concentrations. Ningchun
      exhibited lower germination rate, seedling growth, and lipid peroxidation than
      Xihan when exposed to salinity. The loss of cell viability was correlated with
      the inhibition of root growth induced by NaCl stress. Moreover, treatments with
      H2O2 scavenger dimethylthiourea and catalase (CAT) partly blocked salinity
      induced negative effects on root growth and cell viability. Besides, the
      enhancement of superoxide radical and H2O2 levels, and the stimulation of CAT and
      diamine oxidase (DAO) as well as the inhibition of glutathione reductase (GR)
      were observed in two wheat roots treated with salinity. However, hydroxyl radical
      content increased only in Xihan roots under NaCl treatment, and the changes of
      soluble peroxidase (POD), ascorbate peroxidase (APX), superoxide dismutase (SOD),
      and cell-wall-bound POD activities were different in drought-tolerant Ningchun
      and drought-sensitive Xihan exposed to different NaCl concentrations. In
      conclusion, salinity might induce the loss of cell viability via a pathway
      associated with extracellular H2O2 generation, which was the primary reason
      leading to the inhibition of root growth in two wheat cultivars. Here, it was
      also suggested that increased H2O2 accumulation in the roots of drought-tolerant
      Ningchun might be due to decreased POD and GR activities as well as enhanced cell
      wall-bound POD and DAO ones, while the inhibition of APX and GR as well as the
      stimulation of SOD and DAO was responsible for the elevation of H2O2 level in
      drought-sensitive Xihan roots. 

PMID- 24318674
TI  - Chromosome numbers, characterization of chromosomal pairing during meiosis,
      origin and natural propagation in polyploid cytotypes (4x, 5x and 6x) of
      Agrimonia eupatoria L. (Rosaceae) in northwest Himalayas (India).
AB  - Despite the presence of intraspecific polyploidy (2x, 4x, 5x and 6x) in Agrimonia
      eupatoria, origin of these cytotypes has never been addressed adequately. The aim
      of the present study was to record the original chromosome counts and
      characterize chromosomal pairing during meiosis and microsporogenesis in the 5x
      cytotype, and discussing the hypothesis regarding the possible origin of
      polyploid cytotypes (4x, 5x and 6x) in the species. The geographical distribution
      pattern of cytotypes in the Indian Himalayas and elsewhere has also been
      analyzed. The present meiotic analysis revealed three chromosomes counts, the
      tetraploid (2n = 4x = 56), the pentaploid (2n = 5x = 70) and the hexaploid (2n =
      6x = 84) cytotypes based on x = 14. Meiotic course was perfectly normal in the 4x
      and 6x cytotypes resulting into high pollen fertility (94-100 %). Meiotic course
      in the imbalanced 5x cytotype has been found to be irregular characterized by the
      presence of high frequency of univalents at diakinesis and metaphase-I. Abnormal
      meiotic course contributed towards high pollen sterility (74-88 %). Even the
      apparently fertile/stained pollen grains were of irregular shape and of
      heterogeneous sizes. Meiotic behaviour of the 5x cytotype is like typical of
      allopolyploid. Individuals of 5x cytotype did not produce seeds and propagate
      vegetatively (root suckers) while 4x and 6x cytotypes exploited sexual (seeds) as
      well as vegetative means for propagation. Chromosomal pairing in pentaploid
      cytotype is like typical of an allopolyploid and we assume that it might have
      originated owing to natural inter-cytotype hybridization between 4x and 6x
      cytotypes in a mixed population. Analysis of geographical distribution pattern of
      cytotypes shows that Indian Himalayas represent the most cytotype-diverse region
      for A. eupatoria with the existence of all the four cytotypes (2x, 4x, 5x, 6x).
      This shows the dynamic nature of the species at chromosomal level in this part of
      the world.

PMID- 24318675
TI  - Hydrogen sulfide is involved in maintaining ion homeostasis via regulating plasma
      membrane Na+/H+ antiporter system in the hydrogen peroxide-dependent manner in
      salt-stress Arabidopsis thaliana root.
AB  - Hydrogen sulfide (H2S) and hydrogen peroxide (H2O2) function as the signaling
      molecules in plants responding to salt stresses. The present study presents a
      signaling network involving H2S and H2O2 in salt resistance pathway of the
      Arabidopsis root. Arabidopsis roots were sensitive to 100 mM NaCl treatment,
      which displayed a great increase in electrolyte leakage (EL) and Na(+)/K(+) ratio
      under salt stress. The treatment of H2S donors sodium hydrosulfide (NaHS)
      enhanced the salt tolerance by maintaining a lower Na(+)/K(+) ratio. In addition,
      the inhibition of root growth under salt stress was removed by H2S. Further
      studies indicated that H2O2 was involved in H2S-induced salt tolerance pathway.
      H2S induced the production of the endogenous H2O2 via regulating the activities
      of glucose-6-phosphate dehydrogenase (G6PDH) and plasma membrane (PM) NADPH
      oxidase, with the treatment with dimethylthiourea (DMTU, an ROS scavenger),
      diphenylene iodonium (DPI, a PM NADPH oxidase inhibitor), or glycerol (G6PDH
      inhibitor) removing the effect of H2S. Treatment with amiloride (an inhibitor of
      PM Na(+)/H(+) antiporter) and vanadate (an inhibitor of PM H(+)-ATPase) also
      inhibited the activity of H2S on Na(+)/K(+) ratio. Through an analysis of
      quantitative real-time polymerase chain reaction and Western blot, we found that
      H2S promoted the genes expression and the phosphorylation level of PM H(+)-ATPase
      and Na(+)/H(+) antiporter protein level. However, when the endogenous H2O2 level
      was inhibited by DPI or DMTU, the effect of H2S on the PM Na(+)/H(+) antiporter
      system was removed. Taken together, H2S maintains ion homeostasis in the H2O2
      dependent manner in salt-stress Arabidopsis root.

PMID- 24318676
TI  - Cyst geometry in the egg chambers of Calliphora erythrocephala Mg. (Diptera:
      Calliphoridae) ovaries.
AB  - In the germarium of polytrophic ovarioles of Calliphora erythrocephala (Mg.) fly,
      four mitotic divisions of cystoblasts give rise to 16-cell germ-line cysts. One
      cell differentiates into an oocyte, while the remaining 15 cells become nurse
      cells. Concomitantly actin-rich ring canals are formed at the intercellular
      junctions. The present study considers a mutual arrangement of the ring canals
      formed after the second to fourth mitoses relative to the ring canal formed after
      the first mitotic division in different regions of the germarium and egg
      chambers. During the cyst formation and its movement to the posterior end of the
      germarium, the ring canals are displaced relative to one another, thereby giving
      different branching variants of the cyst. The pattern of cell interconnections
      becomes stable in germarium region 2b and does not change during the cyst
      movement along the ovariole despite the cyst polarizes and increases in size. 

PMID- 24318677
TI  - Defect of suppression of inflammasome-independent interleukin-8 secretion from
      SW982 synovial sarcoma cells by familial Mediterranean fever-derived pyrin
      mutations.
AB  - Familial Mediterranean fever (FMF) is a recessive inherited autoinflammatory
      syndrome. Patients with FMF have symptoms such as recurrent fever and abdominal
      pain, sometimes accompanied by arthralgia. Biopsy specimens have revealed
      substantial neutrophil infiltration into synovia. FMF patients have a mutation in
      the Mediterranean fever gene, encoding pyrin, which is known to regulate the
      inflammasome, a platform for processing interleukin (IL)-1beta. FMF patients
      heterozygous for E148Q mutation, heterozygous for M694I mutation, or combined
      heterozygous for E148Q and M694I mutations, which were found to be major
      mutations in an FMF study group in Japan, suffer from arthritis, the severity of
      which is likely to be lower than in FMF patients with M694V mutations. Expression
      plasmids of wild-type (WT) pyrin and mutated pyrin, such as E148Q, M694I, M694V,
      and E148Q+M694I, were constructed, and SW982 synovial sarcoma cells were
      transfected with these expression plasmids. IL-8 and IL-6 were spontaneously
      secreted from the culture supernatant of SW982 cells without any stimulation,
      whereas IL-1beta and TNF-alpha could not be detected even when stimulated with
      lipopolysaccharide. Notably, two inflammasome components, ASC and caspase-1,
      could not be detected in SW982 cells by Western blotting. IL-8 but not IL-6
      secretion from SW982 cells was largely suppressed by WT pyrin, but less
      suppressed by mutated pyrin, which appeared to become weaker in the order of
      E148Q, M694I, E148Q+M694I, and M694V mutations. As for IL-8 and IL-6, similar
      results were obtained using stable THP-1 cells expressing the WT pyrin or mutated
      pyrins, such as M694V or E148Q, when stimulated by LPS. In addition, IL-8
      secretion from mononuclear cells of FMF patients was significantly higher than
      that of healthy volunteers when incubated on a culture plate. Thus, our results
      suggest that IL-8 secretion from SW982 synovial sarcoma cells suppressed by pyrin
      independently of inflammasome is affected by pyrin mutations, which may reflect
      the activity in FMF arthritis.

PMID- 24318678
TI  - Recollections.
AB  - About 1939, Sam Ruben and Martin Kamen introduced me to the emergent application
      of artificial radio-isotopes in the study of photosynthesis. While my own
      experiments on CO2 fixation by isolated chloroplasts turned out to be negative,
      their laboratory provided me with an informative and exciting experience. Also,
      there were many stimulating contacts with Cornelis van Niel, Robert Emerson, Don
      DeVault and many other outstanding scientists. Efforts on my part to obtain a
      better understanding of intermediary metabolism, eventually led me to Fritz
      Lipmann's laboratory. There I was encouraged to study the metabolic activities of
      cell-free preparations of photosynthetic purple bacteria. Investigations of
      oxidative phosphorylation by isolated bacterial chromatophores in the dark raised
      questions about the possible effects of light on the phosphorylation activities
      of such preparations. Surprisingly, high rates of phosphorylation were observed
      in the light in the absence of molecular oxygen ('light-induced
      phosphorylation'). In this process, adenosine diphosphate (ADP) and inorganic
      phosphate (Pi) could be converted quantitatively into adenosine triphosphate
      (ATP). It was postulated that this process was 'cyclic' in nature, as only
      catalytic concentrations of added electron donors were required. Later, at
      Minnesota, it could be shown that similar chromatophore preparations, in the
      presence of suitable electron donors, could reduce nicotinamide-adenine
      dinucleotide (NAD(+)) to NADH in the light. It was then demonstrated that the
      chromatophores of Rhodospirilum rubrum, as well as the smaller membrane
      components derived from them, must contain the active metabolic components for
      these photosynthetic reactions.These observations, and studies on the kinetics of
      the formation and decay of light-induced free radicals, appeared to demonstrate
      the usefulness of bacterial chromatophores and of their membrane fragments in the
      study of partial reactions of bacterial photosynthesis. Since that time, numerous
      investigators elsewhere have carried out remarkable research on the purification
      and eventual crystallization of distinct bacterial membrane components, capable
      of carrying out well characterized photochemical and electron transport
      reactions. 

PMID- 24318679
TI  - The cytochrome bc 1 complexes of photosynthetic purple bacteria.
AB  - Complete nucleotide sequences are now available for the pet (fbc) operons coding
      for the three electron carrying protein subunits of the cytochrome bc 1 complexes
      of four photosynthetic purple non-sulfur bacteria. It has been demonstrated that,
      although the complex from one of these bacteria may contain a fourth subunit,
      three subunit complexes appear to be fully functional. The ligands to the three
      hemes and the one [2Fe-2S] cluster in the complex have been identified and
      considerable progress has been made in mapping the two quinone-binding sites
      present in the complex, as well as the binding sites for quinone analog
      inhibitors. Hydropathy analyses and alkaline phosphatase fusion experiments have
      provided considerable insight into the likely folding pattern of the cytochrome b
      peptide of the complex and identification of the electrogenic steps associated
      with electron transport through the complex has allowed the orientation within
      the membrane of the electron-carrying groups of the complex to be modeled. 

PMID- 24318680
TI  - Effects of polyploidy on photosynthesis.
AB  - In polyploid plants the photosynthetic rate per cell is correlated with the
      amount of DNA per cell. The photosynthetic rate per unit leaf area is the product
      of the rate per cell times the number of photosynthetic cells per unit area.
      Therefore, the photosynthetic rate per unit leaf area will increase if there is a
      less than proportional increase in cell volume at higher ploidal levels, or if
      cell packing is altered to allow more cells per unit leaf area. In autopolyploids
      (Medicago sativa, C3 species, and Pennisetum americanum, C4 species) there is a
      doubling of photosynthesis per cell and of cell volume in the tetraploid compared
      to the diploid. However, there is a proportional decrease in number of cells per
      unit leaf area with this increase in ploidy such that the rate of photosynthesis
      per leaf area does not change. There is more diversity in the relationship
      between ploidal level (gene dosage) and photosynthetic rates per unit leaf area
      in allopolyploids. This is likely to reflect the effects of natural selection on
      leaf anatomy, and novel genetic interactions from contributed genomes which can
      occur with allopolyploidy. In allopolyploid wheat (C3 species) a higher cell
      volume per unit DNA at the higher ploidal level is negatively correlated with
      photosynthesis rate per unit leaf area. Although photosynthesis per cell
      increases with ploidy, photosynthesis per leaf area decreases, being lowest in
      the allohexaploid, cultivated bread wheat (Triticum aestivum). Alternatively,
      doubling of photosynthetic rate per cell with doubling of DNA, with apparent
      natural selection for decreased cell volume per unit DNA, results in higher rates
      of photosynthesis per leaf area in octaploid compared to tetraploid Panicum
      virgatum (C4) which may be a case of allopolyploidy. Similar responses probably
      occur in Festuca arundinacea. Therefore, in some systems anatomical factors
      affecting photosynthesis are also affected by ploidal level. It is important to
      evaluate that component as well as determining the effect on biochemical
      processes. Current information on polyploidy and photosynthesis in several
      species is discussed with respect to anatomy, biochemistry and bases for
      expressing photosynthetic rates. 

PMID- 24318681
TI  - Characterization of drought resistance in a wild relative of wheat, Triticum
      kotschyi.
AB  - Wild relatives of wheat have served as a genetic source for economically useful
      traits. A better understanding of the mechanisms underlying such traits may be
      useful in the genetic transfer and selection processes. Research was undertaken
      to compare the effects of controlled water stress on photosynthetic parameters in
      Triticum kotschyi, a drought resistant wild wheat and Triticum aestivum cv.
      Lakhish, a drought sensitive wheat cultivar. During stress development, the leaf
      water potential decreased at a slower rate, and the quantum yield of oxygen
      evolution, measured photoacoustically in vivo, decreased to a smaller extent in
      the drought resistant wild wheat than in the wheat cultivar. The decrease in
      quantum yield at water potentials from -0.9 Mpa down to -2.3 Mpa was not
      accompanied by damage to PS II reaction centers as there was no change in
      variable fluorescence. Below -2.3 Mpa the fluorescence yield of both species
      decreased indicating loss of intrinsic efficiency of PS II. The osmotic potential
      of cell sap was found to decrease at the same rate in both species at high
      hydration states. Proline accumulated to a much greater extent in the wild wheat
      as compared to the cultivated wheat as a result of water stress. Drought
      resistance was also examined in relation to thylakoid membrane fluidity measured
      by fluorescence polarization. Thylakoid membrane fluidity was fully maintained in
      the wild wheat, but decreased substantially in the wheat cultivar, at equal
      tissue water potentials below -1.9 Mpa. One mechanism for maintaining the higher
      quantum yield of oxygen evolution during severe stress (at water potentials below
      -1.9 Mpa), may involve the greater stability of thylakoid membrane fluidity in
      the wild wheat. 

PMID- 24318682
TI  - Identification of the major chlorosomal bacteriochlorophylls of the green sulfur
      bacteria Chlorobium vibrioforme and Chlorobium phaeovibrioides; their function in
      lateral energy transfer.
AB  - The chlorosomal bacteriochlorophyll (BChl) composition of the green sulfur
      bacteria Chlorobium vibrioforme and Chlorobium phaeovibrioides was investigated
      by means of normal-phase high-performance liquid chromatography. From both
      species a number of homologues was isolated, which were identified by absorption
      and (252)Cf-plasma desorption mass spectroscopy. Besides BChl d, C. vibrioforme
      contained a significant amount of BChl c, which may provide an explanation for
      the previous observation of at least two spectrally different pools of BChl in
      the chlorosomes of green sulfur bacteria (Otte et al. 1991). C. phaeovibrioides
      contained various homologues of BChl e only. Absorption spectra in acetone of
      BChl c, d and e, as well as bacteriopheophytin e are presented. No systematic
      differences were found for the various homologues of each pigment. In addition to
      farnesol, the mass spectra revealed the presence of various minor esterifying
      alcohols in both species, including phytol, oleol, cetol and 4-undecyl-2
      furanmethanol, as well as an alcohol of low molecular mass, which is tentatively
      assumed to be decenol. 

PMID- 24318683
TI  - Composition of photosynthetic pigments in thylakoid membrane vesicles from
      spinach.
AB  - Thylakoid membranes from spinach were fragmented mechanically and separated into
      vesicles originating from grana and stroma-exposed lamellae (Andreasson et al.
      (1988) Biochim Biophys Acta 936: 339-350). The grana vesicles were further
      fragmented and separated into smaller vesicles originating from different parts
      of the grana (Svensson and Albertsson (1989) Photosynth Res 20: 249-259). All
      vesicles so obtained were analyzed with respect to chlorophyll and carotenoid
      composition by reverse phase HPLC. For all fractions the following relations
      (mole/mole) were found: 1 carotenoid per 4 chlorophyll (a+b), 2 lutein per 5
      chlorophyll b and 5 violaxanthin per 100 chlorophyll (a + b). The contents of
      lutein and neoxanthin were each linearly related to chlorophyll b and beta
      carotene was linearly related to chlorophyll a. 

PMID- 24318684
TI  - Normal-phase HPLC quantitation of chlorophyll a' and phylloquinone in Photosystem
      I particles.
AB  - Fractionated Photosystem (PS) I particles consisting of six, five or two core
      proteins were analyzed by HPLC for chlorophyll (Chl) a' and phylloquinone (PhQ).
      Each particle had a Chl a/P700 molar ratio of 50-55 and contained ca. 2 molecules
      of Chl a' per P700. Deliberate control of eluent composition led to isolated
      elution of PhQ and beta-carotene in the normal-phase chromatogram. Based on these
      a simple HPLC procedure has been established to determine the PhQ/P700 molar
      ratio, which was ca. 2 for the larger two PS I particles and ca. 1 for the
      smallest particle, in line with previous reports. 

PMID- 24318685
TI  - Carotenoids in photosynthesis: Protection of D1 degradation in the light.
AB  - Photosynthesis has been determined with mutants of Anacystis which form different
      amounts of carotenoids. With these cultures a highly significant correlation
      between photosynthetic oxygen evolution and the amounts of synthesized
      carotenoids was observed. In addition, the influence of carotenoids on light
      dependent degradation of thylakoid proteins was investigated with Scenedesmus
      cultures grown in darkness in the presence of norflurazon, an inhibitor of
      carotenoid biosynthesis. Pre-illumination of cells resulted in decrease of
      photosynthetic activity accompanied by loss of the D1 protein. This effect is
      dependent on the length of illumination, and the light intensity, and increased
      when carotenoid content was lowered during previous growth of the norflurazon
      treated cultures. 

PMID- 24318686
TI  - Photosystem II reaction centres stay intact during low temperature
      photoinhibition.
AB  - Photoinhibition of photosynthesis was studied in intact barley leaves at 5 and 20
      degrees C, to reveal if Photosystem II becomes predisposed to photoinhibition at
      low temperature by 1) creation of excessive excitation of Photosystem II or, 2)
      inhibition of the repair process of Photosystem II. The light and temperature
      dependence of the reduction state of QA was measured by modulated fluorescence.
      Photon flux densities giving 60% of QA in a reduced state at steady-state
      photosynthesis (300 MUmol m(-2)s(-1) at 5 degrees C and 1200 MUmol m(-2)s(-1) at
      20 degrees C) resulted in a depression of the photochemical efficiency of
      Photosystem II (Fv/Fm) at both 5 and 20 degrees C. Inhibition of Fv/Fm occurred
      with initially similar kinetics at the two temperatures. After 6h, Fv/Fm was
      inhibited by 30% and had reached steady-state at 20 degrees C. However, at 5
      degrees C, Fv/Fm continued to decrease and after 10h, Fv/Fm was depressed to 55%
      of control. The light response of the reduction state of QA did not change during
      photoinhibition at 20 degrees C, whereas after photoinhibition at 5 degrees C,
      the proportion of closed reaction centres at a given photon flux density was 10
      20% lower than before photoinhibition.Changes in the D1-content were measured by
      immunoblotting and by the atrazine binding capacity during photoinhibition at
      high and low temperatures, with and without the addition of chloramphenicol to
      block chloroplast encoded protein synthesis. At 20 degrees C, there was a close
      correlation between the amount of D1-protein and the photochemical efficiency of
      photosystem II, both in the presence or in the absence of an active repair cycle.
      At 5 degrees C, an accumulation of inactive reaction centres occurred, since the
      photochemical efficiency of Photosystem II was much more depressed than the loss
      of D1-protein. Furthermore, at 5 degrees C the repair cycle was largely inhibited
      as concluded from the finding that blockage of chloroplast encoded protein
      synthesis did not enhance the susceptibility to photoinhibition at 5 degrees C.It
      is concluded that, the kinetics of the initial decrease of Fv/Fm was determined
      by the reduction state of the primary electron acceptor QA, at both temperatures.
      However, the further suppression of Fv/Fm at 5 degrees C after several hours of
      photoinhibition implies that the inhibited repair cycle started to have an effect
      in determining the photochemical efficiency of Photosystem II. 

PMID- 24318687
TI  - A tribute to Hugo P. Kortschak: The man, the scientist and the discoverer of C4
      photosynthesis.
AB  - Hugo P. Kortschak, a shy, quiet Quaker with unbelievable generosity toward
      mankind; an accomplished musician; and a dedicated, tenacious, and brilliant
      scientist, who spent his entire professional career working for a single employer
      in a commercially-oriented research organization, made one of the outstanding
      contributions to biological science of the past century. With his colleagues in
      the Hawaiian sugar industry, he discovered the C4 pathway of photosynthesis. 

PMID- 24318688
TI  - Normobaric hypoxia training causes more weight loss than normoxia training after
      a 4-week residential camp for obese young adults.
AB  - BACKGROUND: Intermittent normobaric hypoxia training, an alternative to altitude
      training for athletes, may be beneficial to treat overweight and obesity. The
      purpose of this study is to investigate whether normobaric hypoxia training
      combined with low-caloric diet has the additive effect on weight loss compared
      with normoxia training in obese young adults. METHODS: Twenty-two subjects (age
      17-25 years, body mass index >27.5 kg/m(2)) were recruited for a 4-week
      residential camp of weight loss with low caloric intake, and trained at 60-70%
      maximal heart rate of aerobics and 40-50% of maximal strength of training. They
      were randomly assigned to either a normobaric hypoxia (HT, FiO2 = 16.4-14.5 %) or
      normoxia training group (NT, FiO2 = 21%), and subjects in HT and NT groups
      experienced weekly 16-h normoxia and 6-h hypoxia or 22-h normoxia training,
      respectively. Body composition, resting blood pressure (BP) and brachial-ankle
      pulse wave velocity (baPWV) were determined before and after the intervention.
      RESULTS: Weight loss was found in HT (-6.9 kg or -7.0%, p < 0.01) and NT groups (
      4.3 kg or -4.2%, p < 0.01) significantly, and the former lost more weight than
      the latter (p < 0.01). Hypoxia training improved systolic BP (-7.6%) and mean BP
      (-7.1%) significantly (p < 0.05) despite having no effect on baPWV. CONCLUSION:
      Four weeks of normobaric hypoxia residential training with low caloric diet has
      an additive improvement on weight loss. It seems that normobaric hypoxia training
      might be a promising method to treat obesity.

PMID- 24318692
TI  - Enzymatic aerobic alkene cleavage catalyzed by a Mn(3+) -dependent proteinase a
      homologue.

PMID- 24318693
TI  - Awareness with explicit recall during general anaesthesia: current status and
      issues.

PMID- 24318694
TI  - Should anaesthetists stop infusing isotonic saline?

PMID- 24318691
TI  - Dissecting the molecular basis of the role of the O-mannosylation pathway in
      disease: alpha-dystroglycan and forms of muscular dystrophy.
AB  - Dystroglycanopathies form a subgroup of muscular dystrophies that arise from
      defects in enzymes that are implicated in the recently elucidated O-mannosylation
      pathway, thereby resulting in underglycosylation of alpha-dystroglycan. The
      emerging identification of additional brain proteins modified by O-mannosylation
      provides a broader context for interpreting the range of neurological
      consequences associated with dystroglycanopathies. This form of glycosylation is
      associated with protein mucin-like domains that present numerous serine and
      threonine residues as possible sites for modification. Furthermore, the O-Man
      glycans coexist in this region with O-GalNAc glycans (conventionally associated
      with such protein sequences), thus resulting in a complex glycoconjugate
      landscape. Sorting out the relationships between the various molecular defects in
      glycosylation and the modes of disease presentation, as well as the regulatory
      interplay among the O-Man glycans and the effects on other modes of glycosylation
      in the same domain, is challenging. Here we provide a perspective on chemical
      biology approaches employing synthetic and analytical methods to address these
      questions. 

PMID- 24318695
TI  - Perioperative melatonin: not ready for prime time.

PMID- 24318696
TI  - Managing chronic pain: a clinical challenge: new SIGN guidelines provide a
      practical evidence-based approach and identify research gaps.

PMID- 24318697
TI  - Demystifying propensity scores.

PMID- 24318698
TI  - Bispectral index monitors, non-invasive cardiac output monitors, and
      haemodynamics of induction agents.

PMID- 24318699
TI  - Bispectral index-guided induction of general anaesthesia.

PMID- 24318700
TI  - Reply from the authors.

PMID- 24318701
TI  - Fourth step for ultrasound-guided central vein catheterization.

PMID- 24318702
TI  - Human factors view of preoperative assessment.

PMID- 24318703
TI  - Reply from the authors.

PMID- 24318704
TI  - Is no nausea worth a little insulin?

PMID- 24318705
TI  - The safety profile of neuraxial magnesium has not been properly addressed.

PMID- 24318706
TI  - Monitoring anaesthetic gas concentrations in the exhaust of the cardiopulmonary
      bypass oxygenator.

PMID- 24318707
TI  - Reply from the authors.

PMID- 24318708
TI  - Intravenous or perineural dexamethasone for interscalene brachial plexus block:
      the equivalence not yet proven.

PMID- 24318709
TI  - Evidence-based language.

PMID- 24318710
TI  - Dexamethasone for increasing analgesic duration of single-shot inter-scalene
      block.

PMID- 24318711
TI  - Ethnicity and acute kidney injury: the correct definition of acute kidney injury?

PMID- 24318712
TI  - Ethnicity and acute kidney injury: the correct definition of acute kidney injury?

PMID- 24318713
TI  - Organ failure related to ethnicity.

PMID- 24318714
TI  - Pharmacological perioperative brain neuroprotection: nimodipine?

PMID- 24318715
TI  - Reply from the authors.

PMID- 24318723
TI  - Hepatic resection for colorectal metastases.
AB  - The liver represents a common site for metastasis in colorectal cancer.
      Improvements in patient selection and surgical techniques has resulted in
      improved outcomes following hepatic metastasectomy with large series reporting 5-
      and 10-year overall survival rates of 40% and 20%, respectively. In recent years,
      criteria for resectability has expanded with the use of forced liver hypertrophy
      and staged resection. The role of perioperative chemotherapy remains
      controversial with a slight increase in survival and operative morbidity.

PMID- 24318724
TI  - Antitubercular and antibacterial activity of quinonoid natural products against
      multi-drug resistant clinical isolates.
AB  - Multi-drug resistant Mycobacterium tuberculosis and other bacterial pathogens
      represent a major threat to human health. In view of the critical need to augment
      the current drug regime, we have investigated therapeutic potential of five
      quinonoids, viz. emodin, diospyrin, plumbagin, menadione and thymoquinone,
      derived from natural products. The antimicrobial activity of quinonoids was
      evaluated against a broad panel of multi-drug and extensively drug-resistant
      tuberculosis (M/XDR-TB) strains, rapid growing mycobacteria and other bacterial
      isolates, some of which were producers of beta-lactamase, Extended-spectrum beta
      lactamase (ESBL), AmpC beta-lactamase, metallo-beta-lactamase (MBL) enzymes, as
      well as their drug-sensitive ATCC counterparts. All the tested quinones exhibited
      antimycobacterial and broad spectrum antibacterial activity, particularly against
      M. tuberculosis (lowest MIC 0.25 ug/mL) and Gram-positive bacteria (lowest MIC <4
      ug/mL) of clinical origin. The order of antitubercular activity of the tested
      quinonoids was plumbagin > emodin ~ menadione ~ thymoquinone > diospyrin, whereas
      their antibacterial efficacy was plumbagin > menadione ~ thymoquinone > diospyrin
      > emodin. Furthermore, this is the first evaluation performed on these quinonoids
      against a broad panel of drug-resistant and drug-sensitive clinical isolates, to
      the best of our knowledge.

PMID- 24318726
TI  - Perspectives on the Royal College of Physicians and Surgeons of Canada new
      subspecialty program in pain medicine.
AB  - PURPOSE: This article describes the rationale for the creation of pain medicine
      as a subspecialty in Canada and outlines a brief history of its development.
      PRINCIPAL FINDINGS: For pain medicine to be designated a Royal College
      subspecialty, it had to meet three requirements: offer sufficient scientific
      breadth and depth, prove a clearly identifiable unique field of practice, and
      show a societal need. The application process for subspecialty status was
      initiated in 2007, and it is anticipated that the first trainees in pain medicine
      will start their training in July 2014. This article outlines the variety of
      Royal College subspecialty entry routes as well as the proposed training
      objectives, curriculum, assessment of competency, practice-eligibility route to
      certification, and accreditation of training programs across Canada. CONCLUSION:
      With the inception of this subspecialty, the treatment of acute pain, cancer
      pain, and chronic non-cancer pain will be further integrated within the Canadian
      healthcare system.

PMID- 24318725
TI  - Ginkgo biloba extract reducing myocardium cells apoptosis by regulating apoptotic
      related proteins expression in myocardium tissues.
AB  - The Bax, cyt-c and caspase-3 proteins play an important role in regulating the
      myocardial apoptosis. Although very little is known about the specific signal
      pathways modulated by Ginkgo biloba extract (GBE), it seems advisable to suppose
      that GBE-induced antiapoptotic effect might be attributed to the regulation of
      the expression of these proteins. Our aim was to investigate whether GBE could
      attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its
      potential mechanisms. In the myocardium ischemia reperfusion (IR) rat model,
      treatment of GBE (400 mg/kg) significantly decreased the cardiomyocyte cell
      apoptosis and myocardium infarction. Immunohistochemical analysis showed that GBE
      significantly inhibited I/R-induced increase of myocardial Bax, caspase-3, and
      cyt-c proteins expression. Western blot analysis confirmed results of
      immunohistochemical analysis. It is most likely that multiple pathways are
      involved in IR-induced apoptosis in rat myocardium cells. Therefore, these
      results demonstrate that GBE exhibits significant protective effect against
      myocardial I/R injury in rat heart, which is related to down-regulate Bax, cyt-c
      and caspase-3. Bcl-2 overexpression might prevent IR-induced apoptosis by
      inhibiting cytochrome c release from the mitochondria and block activation of
      caspase-3.

PMID- 24318727
TI  - Selective bilateral main stem bronchial intubation for the management of severe
      respiratory distress syndrome due to iatrogenic carinal perforation.

PMID- 24318728
TI  - From the Journal archives: Early clinical evaluation of enflurane: the cost of
      progress.

PMID- 24318729
TI  - Evolution at two levels of gene expression in yeast.
AB  - Despite the greater functional importance of protein levels, our knowledge of
      gene expression evolution is based almost entirely on studies of mRNA levels. In
      contrast, our understanding of how translational regulation evolves has lagged
      far behind. Here we have applied ribosome profiling--which measures both global
      mRNA levels and their translation rates--to two species of Saccharomyces yeast
      and their interspecific hybrid in order to assess the relative contributions of
      changes in mRNA abundance and translation to regulatory evolution. We report that
      both cis- and trans-acting regulatory divergence in translation are abundant,
      affecting at least 35% of genes. The majority of translational divergence acts to
      buffer changes in mRNA abundance, suggesting a widespread role for stabilizing
      selection acting across regulatory levels. Nevertheless, we observe evidence of
      lineage-specific selection acting on several yeast functional modules, including
      instances of reinforcing selection acting at both levels of regulation. Finally,
      we also uncover multiple instances of stop-codon readthrough that are conserved
      between species. Our analysis reveals the underappreciated complexity of post
      transcriptional regulatory divergence and indicates that partitioning the search
      for the locus of selection into the binary categories of "coding" versus
      "regulatory" may overlook a significant source of selection, acting at multiple
      regulatory levels along the path from genotype to phenotype.

PMID- 24318730
TI  - Ribosome profiling reveals post-transcriptional buffering of divergent gene
      expression in yeast.
AB  - Understanding the patterns and causes of phenotypic divergence is a central goal
      in evolutionary biology. Much work has shown that mRNA abundance is highly
      variable between closely related species. However, the extent and mechanisms of
      post-transcriptional gene regulatory evolution are largely unknown. Here we used
      ribosome profiling to compare transcript abundance and translation efficiency in
      two closely related yeast species (S. cerevisiae and S. paradoxus). By comparing
      translation regulatory divergence to interspecies differences in mRNA sequence
      features, we show that differences in transcript leaders and codon bias
      substantially contribute to divergent translation. Globally, we find that
      translation regulatory divergence often buffers species differences in mRNA
      abundance, such that ribosome occupancy is more conserved than transcript
      abundance. We used allele-specific ribosome profiling in interspecies hybrids to
      compare the relative contributions of cis- and trans-regulatory divergence to
      species differences in mRNA abundance and translation efficiency. The mode of
      gene regulatory divergence differs for these processes, as trans-regulatory
      changes play a greater role in divergent mRNA abundance than in divergent
      translation efficiency. Strikingly, most genes with aberrant transcript abundance
      in F1 hybrids (either over- or underexpressed compared to both parent species)
      did not exhibit aberrant ribosome occupancy. Our results show that interspecies
      differences in translation contribute substantially to the evolution of gene
      expression. Compensatory differences in transcript abundance and translation
      efficiency may increase the robustness of gene regulation. 

PMID- 24318731
TI  - Does movement variability increase or decrease when a simple wrist task is
      performed during acute wrist extensor muscle pain?
AB  - PURPOSE: The goal of complex tasks can be maintained despite variability in the
      movements of the multiple body segments involved in the task (VAR(elements)).
      This variability increases in acute pain and may enable the nervous system to
      search for less painful/injurious movement options. It is unclear whether
      VAR(elements) increases when pain challenges simple tasks with fewer movement
      options, yet maintain successful attainment of the goal. We hypothesised that
      during acute pain related to a simple movement: (1) the task goal would be
      maintained; (2) VAR(elements) would be increased; and (3) if VAR(elements)
      increased during pain, it would decrease over time. METHODS: Movements of the
      right wrist/forearm were recorded with a three-dimensional motion analysis system
      and during a repetitive radial-ulnar deviation task between two target angle
      ranges (the task goal). We measured success of attaining the goal (repetitions
      that reached the target range and total absolute error in degrees), and
      variability in the motion of wrist flexion-extension and forearm pronation
      supination (VAR(elements)). Fourteen healthy participants performed the task in
      one session before, during, and after wrist extensor muscle pain induced with
      hypertonic saline, and in another session without pain. RESULTS: The task goal
      was maintained during acute pain. However, VAR(elements) in other motion planes
      either reduced (pronation-supination) or did not change (flexion-extension).
      Thus, variability of task elements is constrained, rather than increased, in
      simple tasks. CONCLUSIONS: These data suggest the nervous system adapts simple
      tasks with limited degrees of freedom by reduction of VAR(elements) rather than
      the increase observed for more complex tasks.

PMID- 24318732
TI  - Methods of repair for obstetric anal sphincter injury.
AB  - BACKGROUND: Anal sphincter injury during childbirth - obstetric anal sphincter
      injuries (OASIS) - are associated with significant maternal morbidity including
      perineal pain, dyspareunia (painful sexual intercourse) and anal incontinence,
      which can lead to psychological and physical sequelae. Many women do not seek
      medical attention because of embarrassment. The two recognised methods for the
      repair of damaged external anal sphincter (EAS) are end-to-end (approximation)
      repair and overlap repair. OBJECTIVES: To compare the effectiveness of overlap
      repair versus end-to-end repair following OASIS in reducing subsequent anal
      incontinence, perineal pain, dyspareunia and improving quality of life. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 September 2013) and reference lists of retrieved studies. SELECTION
      CRITERIA: Randomised controlled trials comparing different techniques of
      immediate primary repair of EAS following OASIS. DATA COLLECTION AND ANALYSIS:
      Trial quality was assessed independently by all authors. MAIN RESULTS: Six
      eligible trials, of variable quality, involving 588 women, were included. There
      was considerable heterogeneity in the outcome measures, time points and reported
      results. Meta-analyses showed that there was no statistically significant
      difference in perineal pain (risk ratio (RR) 0.08, 95% confidence interval (CI)
      0.00 to 1.45, one trial, 52 women), dyspareunia (average RR 0.77, 95% CI 0.48 to
      1.24, two trials, 151 women), flatus incontinence (average RR 1.14, 95% CI 0.58
      to 2.23, three trials, 256 women) between the two repair techniques at 12 months.
      However, it showed a statistically significant lower incidence of faecal urgency
      (RR 0.12, 95% CI 0.02 to 0.86, one trial, 52 women), and lower anal incontinence
      score (standardised mean difference (SMD) -0.70, 95% CI -1.26 to -0.14, one
      trial, 52 women) in the overlap group. The overlap technique was also associated
      with a statistically significant lower risk of deterioration of anal incontinence
      symptoms over 12 months (RR 0.26, 95% CI 0.09 to 0.79, one trial, 41 women).
      There was no significant difference in quality of life. At 36 months follow-up,
      there was no difference in flatus incontinence (average RR 1.12, 95% CI 0.63 to
      1.99, one trial, 68 women) or faecal incontinence (average RR 1.01, 95% CI 0.34
      to 2.98, one trial, 68 women). AUTHORS' CONCLUSIONS: The data available show that
      at one-year follow-up, immediate primary overlap repair of the external anal
      sphincter compared with immediate primary end-to-end repair appears to be
      associated with lower risks of developing faecal urgency and anal incontinence
      symptoms. At the end of 36 months there appears to be no difference in flatus or
      faecal incontinence between the two techniques. However, since this evidence is
      based on only two small trials, more research evidence is needed in order to
      confirm or refute these findings.

PMID- 24318734
TI  - Chemical stimuli in host-habitat location byLeptopilina heterotoma (Thomson)
      (Hymenoptera: Eucoilidae), a parasite ofDrosophila.
AB  - Chemical stimuli play an important role in the process of searching for a host
      habitat by parasitic wasps. Volatile compounds originating from host habitats
      and/or hosts are the cues that enable such a location.Leptopilina heterotoma, a
      larval parasite ofDrosophila, is attracted to the food of its host, baker's
      yeast. Analysis of the fermentation products of baker's yeast, using a mass
      spectrometer, and olfactometer studies indicate that three fermentation products
      of this yeast, the main component of the host habitat in our laboratory,
      attractL. heterotoma: ethanol (5%), ethyl acetate (10(-2), 10(-3)%), and
      acetaldehyde (1%). A combination of these three compounds, however, cannot
      compete with baker's yeast in attracting the parasites. Thus other factors, such
      as different compounds, concentrations, and/or combinations, also, play a role
      and remain to be tested.Leptopilina heterotoma does not use host-related
      olfactory cues in long-distance habitat location as it cannot distinguish between
      host habitat and host habitat with hosts. 

PMID- 24318735
TI  - Analysis of trichome exudate from mite-resistant geraniums.
AB  - Trichome exudate from mite-resistant geraniums (Pelargonium horlorum) was
      analyzed, principally by mass spectrometry and NMR spectroscopy. The exudate was
      found to consist of two anacardic acid derivatives,o-pentadecenylsalicylic acid
      ando-heptadecenylsalicylic acid. Bioassays established a moderate toxicity of
      these compounds to the two-spotted spider mite,Tetranychus urticae. The
      production of these compounds in geraniums was correlated with the two
      complementary dominant genes previously reported for host resistance to spider
      mites. 

PMID- 24318733
TI  - Hypoxia shifts activity of neuropeptide Y in Ewing sarcoma from growth-inhibitory
      to growth-promoting effects.
AB  - Ewing sarcoma (ES) is an aggressive malignancy driven by an oncogenic fusion
      protein, EWS-FLI1. Neuropeptide Y (NPY), and two of its receptors, Y1R and Y5R
      are up-regulated by EWS-FLI1 and abundantly expressed in ES cells. Paradoxically,
      NPY acting via Y1R and Y5R stimulates ES cell death. Here, we demonstrate that
      these growth-inhibitory actions of NPY are counteracted by hypoxia, which
      converts the peptide to a growth-promoting factor. In ES cells, hypoxia induces
      another NPY receptor, Y2R, and increases expression of dipeptidyl peptidase IV
      (DPPIV), an enzyme that cleaves NPY to a shorter form, NPY3-36. This truncated
      peptide no longer binds to Y1R and, therefore, does not stimulate ES cell death.
      Instead, NPY3-36 acts as a selective Y2R/Y5R agonist. The hypoxia-induced
      increase in DPPIV activity is most evident in a population of ES cells with high
      aldehyde dehydrogenase (ALDH) activity, rich in cancer stem cells (CSCs).
      Consequently, NPY, acting via Y2R/Y5Rs, preferentially stimulates proliferation
      and migration of hypoxic ALDHhigh cells. Hypoxia also enhances the angiogenic
      potential of ES by inducing Y2Rs in endothelial cells and increasing the release
      of its ligand, NPY3-36, from ES cells. In summary, hypoxia acts as a molecular
      switch shifting NPY activity away from Y1R/Y5R-mediated cell death and activating
      the Y2R/Y5R/DPPIV/NPY3-36 axis, which stimulates ES CSCs and promotes
      angiogenesis. Hypoxia-driven actions of the peptide such as these may contribute
      to ES progression. Due to the receptor-specific and multifaceted nature of NPY
      actions, these findings may inform novel therapeutic approaches to ES. 

PMID- 24318736
TI  - Attraction of bark beetles (Coleoptera: Scolytidae) to a pheromone trap :
      Experiment and mathematical models.
AB  - The movement of bark beetles near an attractive pheromone source is described in
      terms of mathematical models of the diffusion type. To test the models, two
      release experiments involving 47,000 marked spruce bark beetles [Ips typographus
      (L.)] were performed. The attractive source was a pheromone trap, surrounded by
      eight concentric rings with eight passive trap stations on each ring. Captures
      were recorded every 2-10 minutes for the pheromone trap and once for the passive
      traps. The models were fitted to the distribution in time of the central
      pheromone trap catch and to the spatial distribution of catch among the passive
      traps. The first model that gives a reasonable fit consists of two phases: Phase
      one-After release the beetles move according to a diffusion process with drift
      towards the pheromone trap. The strength of the drift is inversely proportional
      to the distance from the traps. Phase two-those beetles attracted to, but not
      caught by, the pheromone trap are no longer influenced by the pheromone, and
      their movement is described by a diffusion process without drift. In phase two we
      work with a loss of beetles, whereas the experiment seems to indicate that the
      loss of beetles in phase one is negligible. As a second model, the following
      modification of phase one is considered: After release the beetles move according
      to a diffusion process without drift, until they start responding to the
      pheromone (with constant probability per unit time), whereafter they start moving
      according to a diffusion process with drift. This study, like other release
      experiments, shows that the efficiency of the pheromone trap is rather low. What
      is specific for the present investigation is that we try to explain this low
      efficiency in terms of dynamic models for insect movement. Two factors seem to
      contribute: Some beetles do not respond to pheromone at all, and some beetles
      disappear again after having been close to the pheromone trap. It also seems that
      the motility of the beetles decreased after they ceased responding to the
      pheromone. Furthermore, the data lend some support to the hypothesis that flight
      exercise increases the response of the beetles to pheromone. 

PMID- 24318737
TI  - Gypsy moth (Lymantria dispar L.) attraction to disparlure enantiomers and the
      olefin precursor in the People's Republic of China.
AB  - Pheromone traps baited with disparlure,cis-7,8-epoxy-2-methyl-octadecane,
      captured males ofLymantria dispar, the gypsy moth, at two widely separated
      locations in the People's Republic of China. The (+) enantiomer of disparlure
      attracted significantly more males than the racemate; addition of olefin reduced
      captures. The duration of the flight period was longer (eight weeks) and peaked
      earlier near Beijing than farther north near Dunhua (five weeks). 

PMID- 24318738
TI  - Receptor cells inIps typographus andDendroctonus micans specific to pheromones of
      the reciprocal genus.
AB  - Olfactory receptor cells were studied electrophysiologically inIps typographus
      andDendroctonus micans. The investigation revealed cells which were keyed to
      pheromone compounds characteristic of the reciprocal genus. Thus, cells keyed
      toexo-brevicomin were found inI. typographus, whereas cells keyed to (+)
      ipsdienol were present inD. micans. Laboratory behavioral tests indicated an
      attractive effect of the two compounds on beetles of the reciprocal genus. InI.
      typographus the effect ofexo-brevicomin predominantly concerned males and
      enhanced their response to the pheromone "ipslure." It is suggested thatexo
      brevicomin serves as an interspecific attractant forI. typographus, which may be
      guided by pheromone compounds of the reciprocal genus in finding suitable
      breeding material. The function of (+)-ipsdienol inD. micans is more uncertain.
      It may be either a pheromone or an interspecific messenger. 

PMID- 24318739
TI  - General approach to synthesis of chiral branched hydrocarbons in high
      configurational purity.
AB  - Configurationally pure (>99.6%) alpha-methylalkanoic acids have been employed to
      prepare chiral hydrocarbon semiochemicals. The stereoisomers of the following
      compounds were synthesized: 13-methylhentriacontane, 15-methyltritriacontane, and
      15,19-dimethyltritriacontane. The first compound was identified earlier as a
      kairomone of the corn earworm while the other two are sex excitants of the stable
      fly. The methods described have broad applicability in asymmetric synthesis. 

PMID- 24318740
TI  - Chemical communication during tandem running inPachycondyla obscuricornis
      (Hymenoptera: Formicidae).
AB  - Communication during tandem running inPachycondyla obscuricornis is chemically
      mediated by a pheromone produced in the pygidial gland, which is composed of a
      cluster of gland cells and an associated reservoir located beween the 6th and 7th
      tergites of the gaster. The secretion of the gland appears to be transferred to
      the hindlegs of a tandem pair leader by a series of self-grooming behaviors that
      occur prior to the formation of a tandem pair. During tandem running, the
      antennae of the following ant are kept in close contact with the leader's
      hindlegs and therefore with the chemical signal that provides a communicative
      bond between individuals. 

PMID- 24318741
TI  - Syntheses of pure (9Z, 11Z), (9E, 11E), (9E, 11Z), and (9Z,11E)-9,11
      hexadecadienals-possible candidate pheromones.
AB  - The title compounds were prepared by six different routes, and recommendations
      are given for the more convenient procedures in laboratory-scale syntheses.
      Modifications in the literature preparations of the 9E,11E and 9E,11Z isomers are
      described. Baseline separation of a prepared mixture of all four isomers of the
      (9Z, 11Z), (9E, 11E), (9E, 11Z), and (9Z, 11E)-9,11-hexadecadienals was achieved
      using GC methods with standard capillary columns. [(13)C]NMR spectroscopy of the
      alkene carbon atoms clearly differentiates between theZ,Z, E,E and eitherE,Z
      orZ,E isomers of the precursor dienols and thus of the dienals. 

PMID- 24318742
TI  - Propheromones that release pheromonal carbonyl compounds in light.
AB  - Pheromonal carbonyl compounds; (Z)-11-hexadecanal, (E)-citral, and 2-heptanone
      were treated with six alcohols to give acetals or ketals, some of which acted as
      propheromones by releasing the pheromonal carbonyl compounds in ultraviolet or
      simulated sunlight. Highest yields of pheromone were obtained from adducts
      prepared witho-nitrobenzyl alcohol ando-nitrophenylethane-1,2-diol. Adducts from
      (Z)-11-hexadecenal and these two alcohols were employed in lures to catch
      diamondback moths,Plutella xylostella (L.). 

PMID- 24318743
TI  - Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or
      without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III
      OVATURE multicenter randomized study.
AB  - BACKGROUND: Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic
      dilemma with limited efficacy from traditional cytotoxic agents. Based on prior
      data suggesting that scheduling alterations of platinum would increase activity,
      the aim of the present study was to assess the potential therapeutic benefit of
      phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing
      potential, when combined with weekly AUC2-carboplatin in PROC patients. PATIENTS
      AND METHODS: A multicenter randomized double-blind placebo controlled phase-III
      study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus
      placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end
      point was progression-free-survival (PFS). Secondary objectives included overall
      survival (OS), response rates, duration of response and quality of life. RESULTS:
      The study was terminated early 14 April 2009, after recruitment of 142 patients
      due to feasibility and recruitment challenges. A total of 142 patients were
      randomized. The groups were well balanced in terms of important baseline
      characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence
      interval (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95% CI = 13.1-33.4); P =
      0.3. The objective response rate and median survival in group 1 versus group 2
      was 0% versus 1% and 38.3 weeks (95% CI 32.0-45.3) versus 45.7 weeks (95% CI 35.6
      58.0), respectively. PXD appeared to be well tolerated. The main reason for dose
      modification in both groups was hematologic toxicity. CONCLUSIONS: Orally
      delivered PXD showed no evidence of clinical activity, when combined with weekly
      AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin
      appeared to be inactive by response criteria in a homogenously defined population
      of PROC. This has implications for the design of future studies.

PMID- 24318744
TI  - The advance transobturator male sling for post-prostatectomy incontinence:
      subjective and objective outcomes with 3 years follow up.
AB  - AIMS: To determine patient-perceived and clinical outcomes of the AdVance sling
      at 3 years follow-up in men with post-prostatectomy incontinence (PPI). METHODS:
      Data was prospectively collected of men with PPI treated with the AdVance male
      sling between February 2008 and March 2010. Twenty-four-hour pad counts and
      weights and patient completed validated questionnaires were obtained pre
      operatively and at 3 years. The primary outcome was improvement in pad count with
      secondary outcomes of questionnaire scores and patient perception of success.
      RESULTS: At a median follow-up of 39 months (IQR: 36-44), we identified 30 men
      meeting inclusion criteria who had the AdVance male sling placed for mild to
      severe PPI. Eighteen (60%) patients were cured (no pad usage or one pad for
      security) and an additional 4 (13%) showed improvement (>=50% reduction in pad
      usage). Eight (27%) patients failed: six patients underwent seven salvage
      procedures including urethral bulking with collagen (n = 1), Virtue perineal
      sling (n = 1), and artificial urinary sphincter (n = 5). There were 16 post
      operative complications: 13 Clavien I, 2 Clavien II, and 1 Clavien IIIb.
      CONCLUSIONS: AdVance male sling is an effective treatment option for PPI
      evidenced by objective improvements in 24-hr pad count and pad weight and patient
      perceived success via validated questionnaires.

PMID- 24318745
TI  - The protective role of ethnic identity for urban adolescent males facing multiple
      stressors.
AB  - Having a connection to one's ethnic heritage is considered a protective factor in
      the face of discrimination; however, it is unclear whether the protective effects
      are persistent across multiple stressors. Furthermore, the dimensions of ethnic
      identity that reflect group pride/connection (affirmation) and exploration of the
      meaning of group membership (achievement) may operate differently in the face of
      stress. The present study examined the moderating role of ethnic identity
      affirmation and achievement on concurrent and longitudinal relationships between
      exposure to stress (discrimination, family hardship, exposure to violence) and
      antisocial behavior in a sample of 256 Black and Latino male youth (70% Black)
      living in low-income urban neighborhoods. Using regression analysis, concurrent
      associations were examined at age 18, and longitudinal associations were tested
      18 months later. We found that, among youth experiencing discrimination, high
      levels of achievement and low levels of affirmation predicted greater aggressive
      behavior and delinquency. Low affirmation also predicted more criminal offending
      in the face of discrimination. The two dimensions operated similarly in the
      context of family stress, in which case high levels of affirmation and
      achievement predicted lower levels of antisocial behavior. The findings suggest a
      differential role of the two dimensions of ethnic identity with respect to
      discrimination; furthermore, the coping skills that may be promoted as youth make
      meaning of their ethnic group membership may serve as cultural assets in the face
      of family stress.

PMID- 24318746
TI  - Evaluation of the Edmonton Functional Assessment Tool (EFAT2) within palliative
      care: a pilot study.
AB  - BACKGROUND: There is increasing need for rehabilitation in both cancer and
      palliative care. However, there are few validated outcome measures that are
      suitable for measuring functional performance in this population. The present
      study evaluated the validity, sensitivity and reliability of the Edmonton
      Functional Assessment Tool (EFAT2) within a UK palliative care setting. METHODS:
      Eleven participants aged 65 years and over (mean age 76.5 +/- 6.7 years)
      receiving rehabilitation in a palliative care inpatient setting were studied.
      Concurrent validity was assessed by comparing EFAT2 with the Barthel Index. Inter
      rater reliability of EFAT2 was examined using a sample of four participants
      recruited from a cancer care ward. RESULTS: A significant negative correlation
      was observed between the Barthel Index and EFAT2 (r = -0.765, p = 0.01) and both
      measures were found to be sensitive as determined by Cohen's effect size (EFAT2 =
      0.60, Barthel Index = 0.72). High inter-rater reliability was noted for EFAT2
      (ICC3, 1 = 0.85) and the agreement between scores was confirmed by Bland-Altman
      analysis. CONCLUSIONS: EFAT2 showed concurrent validity with the Barthel Index
      when used to assess the effects of rehabilitation on participants with advanced
      cancer. The tool was sensitive to change and was found to be reliable when used
      by different raters. The findings indicate that EFAT2 might be an appropriate
      outcome measure to use within the palliative care setting. However, the
      feasibility of using EFAT2 needs to be explored and larger studies are required
      to confirm its reliability.

PMID- 24318748
TI  - Morphology, ultrastructure and molecular characterisation of Spiroxys japonica
      Morishita, 1926 (Spirurida: Gnathostomatidae) from Pelophylax nigromaculatus
      (Hallowell) (Amphibia: Ranidae).
AB  - Gnathostomatid nematodes identified morphologically as Spiroxys japonica
      Morishita, 1926 were collected from the dark-spotted frog Pelophylax
      nigromaculatus (Hallowell) (Amphibia: Ranidae) in China. Light and scanning
      electron microscopy were used to study the morphology of this species in detail.
      Previously unreported morphological features are revealed and others corrected.
      In addition, adult nematodes of S. japonica collected from P. nigromaculatus and
      Spiroxys hanzaki Hasegawa, Miyata & Doi, 1998 collected from Andrias japonicus
      (Temminck) (Caudata: Cryptobranchidae) in China and Japan, respectively, and the
      third-stage larva of S. japonica collected from Lithobates catesbeianus (Shaw)
      (Anura: Ranidae) in Japan, were characterised using molecular methods by
      sequencing and analysing ribosomal [large ribosomal DNA (18S) and internal
      transcribed space] and mitochondrial [cytochrome c oxidase subunit 1] target
      regions, respectively. The new morphological and genetic data contributes to a
      more accurate diagnosis of this hitherto little known nematode genus. 

PMID- 24318747
TI  - In vitro antiplasmodial activity of some medicinal plants of Burkina Faso.
AB  - Malaria remains a major public health problem due to the emergence and spread of
      Plasmodium falciparum drug resistance. There is an urgent need to investigate new
      sources of antimalarial drugs which are more effective against Plasmodium
      falciparum. One of the potential sources of antimalarial drugs is traditional
      medicinal plants. In this work, we studied the in vitro antiplasmodial activity
      of chloromethylenic, methanolic, and MeOH/H2O (1/1) crude extracts and decoction
      obtained from eight medicinal plants collected in Burkina Faso and of total
      alkaloids for five plants. Extracts were evaluated in vitro for efficacy against
      Plasmodium falciparum strain K1, which is resistant to chloroquine, pyrimethamine
      and proguanil using the fluorescence-based SYBR Green I assay. The
      antiproliferative activity on human-derived hepatoma cell line HepG2 and Chinese
      hamster ovary (CHO) cells was evaluated using the 3-[4,5-dimethylthyazol-2-yl]
      2,5-diphenyltetrazolium bromide (MTT) test in order to determine the selectivity
      index. Among the plant extracts tested for in vitro antiplasmodial activity, 16
      were considered to be inactive (with IC50 > 10 MUg/ml), six showed a moderate
      activity (5 < IC50 <= 10 MUg/ml), and six were found to have a good in vitro
      activity with IC50 value <= 5 MUg/ml. The highest antiplasmodial activity was
      found for extracts from: the alkaloid leaf extract and the chloromethylenic
      extracts of Combretum fragrans (IC50 = 3 MUg/ml, IC50 = 5 MUg/ml), the total
      alkaloids and the chloromethylenic leaf extracts of Combretum collinum (IC50 = 4
      MUg/ml), the MeOH/H2O leaf extract of Terminalia avicennioides (IC50 = 3.5
      MUg/ml), and the alkaloid leaf extract of Pavetta crassipes (IC50 = 5 MUg/ml).
      Three other extracts showed moderate antiplasmodial activity (5 < IC50 <= 10
      MUg/ml): Terminalia avicennioides and Combretum fragrans methanolic extracts and
      Acacia kirkii alkaloid leaf extract (IC50 = 6.5, 9 and 10 MUg/ml respectively).
      The Terminalia avicennioides crude MeOH/H2O (80:20 v/v) extract of the leaves was
      submitted to a successive liquid/liquid extraction with ethylacetate and n
      butanol respectively. The extracts were investigated for in vitro antiplasmodial
      activity and antioxidant properties using DPPH(.), ABTS(+) and FRAP methods. The
      ethylacetate extract showed the best antiplasmodial activity (7 MUg/ml) and the
      active constituent was isolated as ellagic acid by bioguided fractionation with
      an IC50 = 0.2 MUM on Plasmodium falciparum and SI = 152. Besides, Terminalia
      avicennioides leaf extract and ellagic acid showed a good antioxidant activity.
      Our finding confirms the importance of investigating the antimalarial activity of
      plant species used in traditional medicine. Overall, two plants belonging to the
      Combretaceae family, Combretum fragrans and Combretum collinum appeared to be the
      best candidates and will be further investigated for their antiplasmodial
      properties, in order to isolate the molecules responsible for the antiplasmodial
      activity.

PMID- 24318749
TI  - Auto-Caesarean section: a review of 22 cases.
AB  - The authors have trawled the literature on self-inflicted Caesarean section,
      assessing circumstances and probable motivation; 19/22 cases had sufficient
      information. In seven cases, the apparent intention was to kill the child. In
      four, the action resulted from some form of mental illness. In eight, the woman,
      in the agony of obstructed labour, took matters into her own hands. We think the
      third group would be more numerous if there were more publications from Africa
      and South Asia, where many women give birth without the aid of modern obstetrics.
      The survival rate among the mothers was surprisingly high. 

PMID- 24318750
TI  - The role of inorganic phosphate in the regulation of C4 photosynthesis.
AB  - Inorganic phosphate participates in many fundamental processes within the plant
      cell. Its broad influence on plant metabolism is related to such key operations
      as metabolite transport, enzyme regulation and carbohydrate metabolism in
      general. This review discusses these topics with special emphasis on the role
      assigned to this ubiquitous anion within the C4 pathway of photosynthesis. 

PMID- 24318751
TI  - Heat-stress stimulation of oxygen uptake by Photosystem I involves the reduction
      of superoxide radicals by specific electron donors.
AB  - A Photosystem I submembrane fraction isolated from spinach was used to study the
      mechanism of heat-stress stimulation of oxygen uptake by the photosystem. Various
      artificial electron donors were shown to generate electron transport reactions
      with various degrees of thermally induced stimulation. A strong stimulation was
      observed with durohydroquinone as electron donor with a maximal effect at 50 
      degrees C. The degree of stimulation obtained was independent from the redox
      potential of the electron donors and from their oxidation site because the enzyme
      superoxide dismutase fully inhibited the stimulation. Instead, it is proposed
      that thermal stress causes the release of membrane bound superoxide dismutase
      from the thylakoids thus allowing the reduced form of electron donors with
      specific properties to reduce O2 (-) radicals to H2O2 besides the usual
      disproportionation of O2 (-) into O2 and H2O2. 

PMID- 24318752
TI  - Light-dependent modulation of ribulose-1,5-bisphosphate carboxylase/oxygenase
      activity in the genus Phaseolus.
AB  - Modulation of the activity of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) in low light and darkness was measured in A) 25 genotypes from the four
      cultivated species of Phaseolus (P. vulgaris, P. acutifolius, P. lunatus and P.
      coccineus), B) 8 non-cultivated Phaseolus species, and C) the related species
      Macroptileum atropurpureum. The activity ratio of Rubisco (the ratio of initial
      and total Rubisco activities, which reflects Rubisco carbamylation), and the
      molar activity of fully-activated Rubisco (which primarily reflects the
      inhibition of Rubisco activity by carboxyarabinitol 1-phosphate, CA1P) were
      assayed in leaves from the cultivated species sampled at midday in full sunlight,
      in low light at dusk (60 to 100 MUmol photons m(-2)s(-1)), and after at least 4 h
      in darkness. Dark inhibition of Rubisco molar activity was compared in both
      cultivated and non-cultivated species. In all cultivated genotypes, a significant
      reduction of the activity ratio of Rubisco was measured in leaves sampled at low
      light; however, the molar activity of fully activated Rubisco was not greatly
      reduced in these low light samples. In darkened leaves, molar activities
      substantially declined in most Phaseolus species with 11 of 13 exhibiting greater
      than 60% reduction. In P. vulgaris, the reduction of molar activity was extensive
      (greater than 69%) in all genotypes studied, which included wild progenitors as
      well as ancient and advanced cultivars. These results indicate that at low light
      late in the day, modulation of Rubisco activity is primarily through changes in
      carbamylation state, with CA1P playing a more limited role. By contrast in the
      dark, binding of CA1P dominates the modulation of Rubisco activity in Phaseolus
      in a pattern that appears to be conserved within a species, but can vary
      significantly between species within a genus. The degree of CA1P inhibition in
      Phaseolus was associated with phylogenetic affinities within the genus, as the
      species with extensive dark-inhibition of Rubisco activity tended to be more
      closely related to each other than to species with reduced inhibition of Rubisco
      activity. 

PMID- 24318753
TI  - Effect of trypsin on D1/D 2-cytochrom b 559 Photosystem 2 reaction center complex
      and reaction center from Rhodopseudomonas viridis.
AB  - Proteolytic enzyme (trypsin) was used to structurally alter the RCs isolated from
      plant and bacterium as a way of probing the relation between structure
      (chromophore-apoprotein interactions) and function (photochemical activity). It
      was found that neither spectral characteristics (absorption spectrum, the 4th
      derivative of absorption spectrum) nor photochemical activity (pheophytine
      photoreduction, P680 photooxidation, etc.) were changed dramatically in
      D1/D2/cytochrom b 559 PS 2 reaction center complex digested with trypsin. The PS
      2 RC treated with trypsin migrates by one green band during electrophoresis with
      dodecylmaltoside. The peptides with a molecular mass higher than 3-4 kDa were not
      separated from PS 2 RC. These data indicate that digestion of D1 and D2 proteins
      does not disturb yet the conformation of peptides or their interactions in so
      called 'core' of RC and the native state of pigments. In contrast to that, the RC
      from Rhodopseudomonas viridis treated with enzyme has changed absorption spectrum
      and lost photochemical activity. The stability of the bacterial RC increased
      after exchange of LDAO by dodecylmaltoside. 

PMID- 24318754
TI  - Genes encoding phycobilisome linker polypeptides on the plastid genome of
      Aglaothamnion neglectum (Rhodophyta).
AB  - The genes encoding the phycobilisome anchor protein (apcE) and rod-core linker
      (cpcG) are on the plastid genome of the red alga Aglaothamnion neglectum. The
      apcE gene product is 5' to and in the same operon as the alpha and beta subunit
      genes of allophycocyanin. This arrangement is identical to the arrangement
      observed in many cyanobacteria. The cpcG gene product is 5' to the operon
      encoding the alpha and beta subunits of phycoerythrin, but is transcribed from
      the opposite DNA strand. This gene arrangement is different from that observed in
      cyanobacteria.The amino acid sequences of the A. neglectum anchor protein and rod
      core linker polypeptide, as deduced from the nucleotide sequences of the genes,
      are approximately 50% identical to analogous polypeptides from cyanobacteria and
      another eukaryotic alga Cyanophora paradoxa. The conserved nature of these
      proteins suggests that the structure of the core and the rod-core interface are
      very similar in phycobilisomes of cyanobacteria and eukaryotic red
      algae.Environmental factors such as nutrient availability and light intensity can
      significantly affect the levels of mRNAs encoding the anchor protein and the rod
      core linker polypeptide. Most of these changes are similar to the environmentally
      controlled changes in the levels of phycobiliprotein transcripts of A. neglectum
      (Apt and Grossman 1992b). However, unlike the mRNAs encoding other phycobilisome
      components, the apcE transcript remains high during growth under conditions of
      nutrient deprivation. 

PMID- 24318755
TI  - Long-wavelength absorbing antenna pigments and heterogeneous absorption bands
      concentrate excitons and increase absorption cross section.
AB  - The light-harvesting apparatus of photosynthetic organisms is highly optimized
      with respect to efficient collection of excitation energy from photons of
      different wavelengths and with respect to a high quantum yield of the primary
      photochemistry. In many cases the primary donor is not an energetic trap as it
      absorbs hypsochromically compared to the most red-shifted antenna pigment present
      (long-wavelength antenna). The possible reasons for this as well as for the
      spectral heterogeneity which is generally found in antenna systems is examined on
      a theoretical basis using the approach of thermal equilibration of the excitation
      energy. The calculations show that long-wavelength antenna pigments and
      heterogeneous absorption bands lead to a concentration of excitons and an
      increased effective absorption cross section. The theoretically predicted
      trapping times agree remarkably well with experimental data from several
      organisms. It is shown that the kinetics of the energy transfer from a long
      wavelength antenna pigment to a hypsochromically absorbing primary donor does not
      represent a major kinetic limitation. The development of long-wavelength antenna
      and spectrally heterogeneous absorption bands means an evolutionary advantage
      based on the chromatic adaptation of photosynthetic organelles to spectrally
      filtered light caused by self-absorption. 

PMID- 24318756
TI  - Light dependence of quantum yields of Photosystem II and CO2 fixation in C 3 and
      C 4 plants.
AB  - The light dependence of quantum yields of Photosystem II (PhiII) and of CO2
      fixation were determined in C3 and C4 plants under atmospheric conditions where
      photorespiration was minimal. Calculations were made of the apparent quantum
      yield for CO2 fixation by dividing the measured rate of photosynthesis by the
      absorbed light [A/I=PhiCO2 and of the true quantum yield by dividing the
      estimated true rate of photosynthesis by absorbed light [(A+Rl)/Ia=PhiCO2.],
      where RL is the rate of respiration in the light. The dependence of the
      PhiII/PhiCO2 and PhiII/PhiCO2 (*) ratios on light intensity was then evaluated.
      In both C3 and C4 plants there was little change in the ratio of PhiII/PhiCO2 at
      light intensities equivalent to 10-100% of full sunlight, whereas there was a
      dramatic increase in the ratio at lower light intensities. Changes in the ratio
      of PhiII/PhiCO2 can occur because respiratory losses are not accounted for, due
      to changes in the partitioning of energy between photosystems or changes in the
      relationship between PS II activity and CO2 fixation. The apparent decrease in
      efficiency of utilization of energy derived from PS II for CO2 fixation under low
      light intensity may be due to respiratory loss of CO2. Using dark respiration as
      an estimate of RL, the calculated PhiII/PhiCO2 (*) ratio was nearly constant from
      full sunlight down to approx 5% of full sunlight, which suggests a strong linkage
      between the true rate of CO2 fixation and PS II activity under varying light
      intensity. Measurements of photosynthesis rates and PhiII were made by
      illuminating upper versus lower leaf surfaces of representative C3 and C4
      monocots and dicots. With the monocots, the rate of photosynthesis and the ratio
      of PhiII/PhiCO2 exhibited a very similar patterns with leaves illuminated from
      the adaxial versus the abaxial surface, which may be due to uniformity in anatomy
      and lack of differences in light acclimation between the two surfaces. With
      dicots, the abaxial surface had both lower rates of photosynthesis and lower
      PhiII values than the adaxial surface which may be due to differences in anatomy
      (spongy versus palisade mesophyll cells) and/or light acclimation between the two
      surfaces. However, in each species the response of PhiII/PhiCO2 to varying light
      intensity was similar between the two surfaces, indicating a comparable linkage
      between PS II activity and CO2 fixation. 

PMID- 24318757
TI  - The effect of detergent on the structure and composition of chlorosomes isolated
      from Chloroflexus aurantiacus.
AB  - Isolated chlorosomes, treated with the detergent lithium dodecyl sulfate (LDS),
      can be separated into two green fractions by agarose gel electrophoresis. One
      fraction contains chlorosomes with a full complement of proteins and antenna BChl
      c absorbing at 740 nm, but with a more spherical form than the normal ellipsoid
      shape observed in control chlorosomes. The second fraction was completely devoid
      of proteins but had a similar absorption spectrum. Electron micrographs of the
      protein-free fraction indicated the presence of stain-excluding spheres with
      overall dimensions resembling those of intact chlorosomes (40-100 nm). These
      spheres are probably micelles of BChl c liberated from the chlorosomes during the
      detergent treatment, since similar structures could be produced when purified
      BChl c, dissolved in 1-hexanol, was dispersed in buffer, producing an aggregate
      absorbing at 742 nm. These results suggest that the chlorosome proteins are not
      required to produce an arrangement of BChl c chromophores which gives rise to a
      740 nm absorption peak resembling that of intact chlorosomes. It seems probable,
      however, that proteins have a role in determining the overall shape of the
      chlorosome. Treatment with cross-linking reagents did not prevent the detergent
      induced changes in chlorosome morphology. 

PMID- 24318758
TI  - Purification and crystallization of Photosystem I complex from a phycobilisome
      less mutant of the cyanobacterium Synechococcus PCC 7002.
AB  - An active photosystem (PSI) complex was isolated from a phycobilisome-less mutant
      of the mesophilic cyanobacterium Synechococcus PCC 7002 by a mild procedure.
      Purification of PS I was achieved using a sucrose density gradient and an
      isoelectric focussing subsequent to the extraction of PSI from thylakoids with
      dodecyl-beta-maltoside. Electron microscopy and gel filtration HPLC suggested
      that the isolated complex represents a trimeric form of PSI. The trimeric form
      was resistant to pH or detergent exchange. A 'molecular weight' of 690 kDa to 760
      kDa has been determined for the complex by gel filtration HPLC in several
      detergents or mixtures of detergents.The PSI complex contains the polypeptides of
      the psaA, psaB, psaC, psaD, psaE, psaL gene products and two small polypeptides
      as determined by SDS-PAGE and N-terminal sequencing; its antenna size is 77+/-2
      Chl a/P700. The full set of Fe-S clusters (FA, FB and FX) was observed by EPR
      spectroscopy. A preliminary characterization of crystals obtained from this
      preparation was carried out using SDS-PAGE, optical and EPR spectroscopy. 

PMID- 24318759
TI  - Leaf gas exchange of beech (Fagus sylvatica L.) seedlings in lightflecks: A
      system for measuring rapid changes in CO2 partial pressures.
AB  - A system is described for the measurement of fast transient responses of leaf gas
      exchange to lightflecks. Any chamber adulterates a true signal unless in the
      steady-state; therefore, a procedure for estimating an 'effective chamber volume'
      is presented which is an essential parameter for correcting a measured transient
      signal. A common correction is critically commented on. With the system,
      responses of net photosynthesis to lightflecks as short as 1 s have been observed
      in leaves of seedlings of Fagus sylvatica L. 

PMID- 24318760
TI  - Chlorophyll fluorescence transients in a barley mutant lacking Photosystem I.
AB  - We have compared the properties of a mutant of barley lacking Photosystem I
      (viridis-zb (63) ) with the corresponding wild type using modulated fluorescence
      measurements. The mutant showed two unexpected characteristics. Firstly, there
      was a slow decline in the fluorescence signal in the light which was dependent on
      the presence of O2 at concentrations similar to that in air; 2% O2 in N2 had no
      effect. The observed decline was mainly due to an increase in the non
      photochemical quenching. Secondly, in the absence of O2, saturating light pulses
      caused a pronounced transient decrease in the fluorescence signal; a similar
      effect could also be observed in wild type plants when neither CO2 nor O2 was
      present. 

PMID- 24318761
TI  - Steady-state polarized light spectroscopy of isolated Photosystem I complexes.
AB  - Monomeric and trimeric Photosystem I core complexes from the cyanobacterium
      Synechocystis PCC 6803 and LHC-I containing Photosystem I (PS I-200) complexes
      from spinach have been characterized by steady-state, polarized light
      spectroscopy at 77 K. The absorption spectra of the monomeric and trimeric core
      complexes from Synechocystis were remarkably similar, except for the amplitude of
      a spectral component at long wavelength, which was about twice as large in the
      trimeric complexes. This spectral component did not contribute significantly to
      the CD-spectrum. The (77 K) steady-state emission spectra showed prominent peaks
      at 724 nm (for the Synechocystis core complexes) and at 735 nm (for PS I-200). A
      comparison of the excitation spectra of the main emission band and the absorption
      spectra suggested that a significant part of the excitations do not pass the red
      pigments before being trapped by P-700. Polarized fluorescence excitation spectra
      of the monomeric and trimeric core complexes revealed a remarkably high
      anisotropy (~0.3) above 705 nm. This suggested one or more of the following
      possibilities: 1) there is one red-most pigment to which all excitations are
      directed, 2) there are more red-most pigments but with (almost) parallel
      orientations, 3) there are more red-most pigments, but they are not connected by
      energy transfer. The high anisotropy above 705 nm of the trimeric complexes
      indicated that the long-wavelength pigments on different monomers are not
      connected by energy transfer. In contrary to the Synechocystis core complexes,
      the anisotropy spectrum of the LHC I containing complexes from spinach was not
      constant in the region of the long-wavelength pigments, and decreased
      significantly below 720 nm, the wavelength where the long-wavelength pigments on
      the core complexes start to absorb. These results suggested that in spinach the
      long-wavelength pigments on core and LHC-I are connected by energy transfer and
      have a non-parallel average Qy(0-0) transitions. 

PMID- 24318762
TI  - Properties of inactive Photosystem II centers.
AB  - A fraction (usually in the range of 10-25%) of PS II centers is unable to
      transfer electrons from the primary quinone acceptor QA to the secondary acceptor
      QB. These centers are inactive with respect to O2 evolution since their reopening
      after photochemical charge separation to the S2OA (-) state involves
      predominantly a back reaction to S1QA in the few seconds time range (slower
      phases are also occurring). Several properties of these centers are analyzed by
      fluorescence and absorption change experiments. The initial rise phase Fo-Fpl of
      fluorescence induction under weak illumination reflects both the closure of
      inactive centers and the modulation of the fluorescence yield by the S-states of
      the oxygen-evolving system: We estimate typical relative amplitudes of these
      contributions as, respectively, 65 and 35% of the Fo-Fpl amplitude. The half-rise
      time of this phase is significantly shorter than for the fluorescence induction
      in the presence of DCMU (in which all centers are involved). This finding is
      shown to be consistent with inactive centers sharing the same light-harvesting
      antenna as normal centers, a view which is also supported by comparing the
      dependence of the fluorescence yield on the amount of closed active or inactive
      centers estimated through absorption changes. It is argued that the exponential
      kinetics of the Fo-Fpl phase does not indicate absence of excitation energy
      transfer between the antennas of inactive and active centers. We show that the
      acceptor dichlorobenzoquinone does not restore electron transfer in inactive
      centers, in disagreement with previous suggestions. We confirm, however, the
      enhancement of steady-state electron flow caused by this quinone and suggest that
      it acts by relieving a blocking step involved in the reoxidation of a fraction of
      the plastoquinone pool. Part of the discrepancies between the present results and
      those from previous literature may arise from the confusion of inactive centers
      characterized on a single turnover basis and PS II centers that become blocked
      under steady-state conditions because of deficient reoxidation of their secondary
      acceptors. 

PMID- 24318763
TI  - Inactivation of photosynthetic oxygen evolution by o-phenanthroline and LiClO4 in
      Photosystem 2 of the pea.
AB  - We examined the effects of o-phenanthroline and LiClO4 on oxygen evolution and
      electron transport in the Photosystem 2 complex of the pea. Treatment of
      Photosystem 2 particles with a combination of 3.0 mM o-phenanthroline and 1.0 M
      LiClO4 for 30-40 min at 0 degrees C decreased the oxygen-evolving activity with
      the electron acceptor (either phenyl-p-benzoquinone or 2,6-dichlorophenol
      indophenol) to less than 5% of the original level. However with the same
      treatment, the electron-transport activity from an artificial electron donor, 1,5
      diphenylcarbohydrazide, to 2,6-dichlorophenol indophenol remained at 60% of the
      original activity. The amount of manganese in the Photosystem 2 complex decreased
      in parallel with the loss of oxygen evolution following treatment. These
      observations suggest that the treatment of the Photosystem 2 complex with o
      phenanthroline and LiClO4 inhibits electron transport on the oxygen-evolving side
      much more significantly than on the electron-acceptor side. 

PMID- 24318764
TI  - The GATA and SORLIP motifs in the 3-hydroxy-3-methylglutaryl-CoA reductase
      promoter of Picrorhiza kurrooa for the control of light-mediated expression.
AB  - Light upregulates the expression of 3-hydroxy-3-methylglutaryl-CoA reductase
      (HMGR) in Picrorhiza kurrooa, an endangered medicinal herb. Upstream sequences of
      HMGR of P. kurrooa (PropkHMGR) were analyzed in relation to its role in light
      mediated regulation of gene expression. GATA motif in PropkHMGR exhibited
      stronger DNA-protein interaction with the nuclear extract of dark-exposed plants
      in contrast to SORLIP that exhibited stronger binding with the nuclear extract of
      light-exposed plants. Analysis of PropkHMGR (PropkHMGR-D1, -1,059/-1) and its
      deletion fragments PropkHMGR-D2 (-825/-1), PropkHMGR-D3 (-651/-1), PropkHMGR-D4 (
      452/-1), and PropkHMGR-D5 (-101/-1) in Arabidopsis thaliana showed PropkHMGR to
      regulate gene expression [beta-glucuronidase (GUS) was used as a reporter gene]
      at all the developmental stages but only in actively dividing tissues, excluding
      anthers. Whereas, PropkHMGR-D2 regulated GUS expression in relatively older
      seedlings but the expression was observed only in shoot apical meristem, root
      tips, and anthers. PropkHMGR-mediated gene expression was higher in dark as
      compared to that in the light in Arabidopsis across four temperatures studied. As
      opposed to the results in P. kurrooa, GATA motifs exhibited DNA-protein
      interaction with nuclear extract of light-exposed plants of Arabidopsis. SORLIP
      motifs in Arabidopsis also exhibited DNA-protein interaction with nuclear extract
      of light-exposed plants as in P. kurrooa. Data showed that (1) PropkHMGR
      regulated light-mediated gene expression and (2) GATA motif exhibited an inverse
      relationship between strength of DNA-protein interaction and the gene expression
      whereas the relationship was species specific for SORLIP. 

PMID- 24318765
TI  - Ruminal epithelium transcriptome dynamics in response to plane of nutrition and
      age in young Holstein calves.
AB  - This study assessed the effects of enhanced dietary plane of nutrition (early
      nutritional program (ENH)) on the gene expression pattern of ruminal epithelial
      tissue of young Holstein calves. Male Holstein calves were fed (3 to 42 days of
      age) with reconstituted control milk replacer (MR) (20 % crude protein, 20 % fat;
      1.25 lb solids/calf) plus conventional starter (CON; 19.6 % crude protein, dry
      matter basis) or a high-protein MR (ENH; 28.5 % crude protein, 15 % fat; at
      around 2 % of body weight) plus high-crude protein starter (25.5 % crude protein,
      dry matter basis). The calves were weaned on day 43. Groups of calves in CON and
      ENH treatment were harvested after 5 and 10 weeks of feeding. The ruminal
      epithelium from five calves in each group was used for transcript profiling using
      a bovine oligonucleotide microarray. The postweaning mass of the reticulo-rumen
      was greater (P < 0.01) in calves consuming ENH. Transcriptome analysis revealed
      that 208 genes were altered due to treatment and 587 due to time alone.
      Bioinformatics analysis revealed that "galactose metabolism," "citrate cycle,"
      "pyruvate metabolism," and "basal transcription factors" were the most impacted
      and induced pathways due to feeding ENH; whereas, "valine, leucine, and
      isoleucine biosynthesis" and "glyoxylate and dicarboxylate metabolism" were among
      the most inhibited. The integrated interpretation of the results suggested an
      overall increase in metabolism after weaning, particularly biosynthesis of glycan
      and nucleotide metabolism. Furthermore, the preweaning alterations in the
      transcriptome were mostly associated with cell growth, death, tissue development,
      and cellular morphology. The postweaning response revealed overexpression of
      genes associated with cell adhesion molecules, p53 signaling, and fatty acid
      metabolism. Our results indicated that feeding ENH to young Holstein calves
      elicited a strong transcriptomic response in the ruminal epithelial tissue.

PMID- 24318766
TI  - The alpha-gliadin genes from Brachypodium distachyon L. provide evidence for a
      significant gap in the current genome assembly.
AB  - Brachypodium distachyon, is a new model plant for most cereal crops while gliadin
      is a class of wheat storage proteins related with wheat quality attributes. In
      the published B. distachyon genome sequence databases, no gliadin gene is found.
      In the current study, a number of gliadin genes in B. distachyon were isolated,
      which is contradictory to the results of genome sequencing projects. In our
      study, the B. distachyon seeds were found to have no gliadin protein expression
      by gel electrophoresis, reversed-phase high-performance liquid chromatography and
      Western blotting analysis. However, Southern blotting revealed a presence of more
      than ten copies of alpha-gliadin coding genes in B. distachyon. By means of AS
      PCR amplification, four novel full-ORF alpha-gliadin genes, and 26 pseudogenes
      with at least one stop codon as well as their promoter regions were cloned and
      sequenced from different Brachypodium accessions. Sequence analysis revealed a
      few of single-nucleotide polymorphisms among these genes. Most pseudogenes were
      resulted from a C to T change, leading to the generation of TAG or TAA in-frame
      stop codon. To compare both the full-ORFs and the pseudogenes among Triticum and
      Triticum-related species, their structural characteristics were analyzed. Based
      on the four T cell stimulatory toxic epitopes and two ployglutamine domains,
      Aegilops, Triticum, and Brachypodium species were found to be more closely
      related. The phylogenetic analysis further revealed that B. distachyon was more
      closely related to Aegilops tauschii, Aegilops umbellulata, and the A or D genome
      of Triticum aestivum. The alpha-gliadin genes were able to express successfully
      in E. coli using the functional T7 promoter. The relative and absolute
      quantification of the transcripts of alpha-gliadin genes in wheat was much higher
      than that in B. distachyon. The abundant pseudogenes may affect the
      transcriptional and/or posttranscriptional level of the alpha-gliadin in B.
      distachyon. 

PMID- 24318767
TI  - Protective effects of melatonin against arsenic-induced apoptosis and oxidative
      stress in rat testes.
AB  - This study aimed to investigate the protective effects of melatonin against
      arsenic-induced apoptosis and oxidative stress in rat testes. A total of 27 male
      rats were divided into 3 groups: control (saline: 5 ml kg(-1) day(-1),
      intragastrically), arsenic (sodium arsenite (NaAsO2): 5 mg kg(-1) day(-1),
      intragastrically), and arsenic + melatonin (sodium arsenite (NaAsO2): 5 mg kg(-1)
      day(-1), intragastrically and melatonin: 25 mg kg(-1) day(-1), intraperitoneally)
      group. At the end of 30 days, the rats were killed under anesthesia.
      Histopathological examination showed that testicular injury mediated by arsenic
      was ameliorated by the administration of melatonin. The number of apoptotic germ
      cell was increased, and the number of proliferating cell nuclear antigen (PCNA)
      positive germ cell was decreased in testis after arsenic administration. Our data
      indicate a significant reduction in the activity of terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling, and there was a
      rise in the expression of PCNA in testis of arsenic + melatonin group. The
      decreased superoxide dismutase, catalase, and glutathione peroxidase activities
      as well as increased malondialdehyde levels in testis due to arsenic
      administration were also counteracted by melatonin. These data suggested that
      melatonin has beneficial effects against arsenic-induced testicular damage by
      decreasing morphological damage, germ cell apoptosis, lipid peroxidation, and
      oxidative stress. Our results suggest that melatonin plays a protective role
      against arsenic-induced testicular apoptosis and oxidative stress. 

PMID- 24318768
TI  - Quality assessment of mental health care by people with severe mental disorders:
      a participatory research project.
AB  - This study assessed the perceived quality of care by consumers with severe mental
      disorders. A questionnaire investigating service quality was developed by a
      consumer focus group and filled by 204 consumers. In five areas the negative
      evaluations exceeded or closely approximated the positive ones: choice of
      professionals, waiting times, information about illness and medications. All five
      do not refer to the outcomes of care, but to the concept of responsiveness. The
      results confirmed that people with severe mental disorders can give value
      judgments on various aspects of care. However, even in a service strongly
      oriented towards community care, the consumers' needs in sensitive areas
      concerning choices, respect and autonomy are not met. The application of the
      concept of responsiveness to quality improvement may help services to meet
      consumers' expectations. 

PMID- 24318769
TI  - Cultural Consensus Theory for the ordinal data case.
AB  - A Cultural Consensus Theory approach for ordinal data is developed, leading to a
      new model for ordered polytomous data. The model introduces a novel way of
      measuring response biases and also measures consensus item values, a consensus
      response scale, item difficulty, and informant knowledge. The model is extended
      as a finite mixture model to fit both simulated and real multicultural data, in
      which subgroups of informants have different sets of consensus item values. The
      extension is thus a form of model-based clustering for ordinal data. The
      hierarchical Bayesian framework is utilized for inference, and two posterior
      predictive checks are developed to verify the central assumptions of the model. 

PMID- 24318771
TI  - Bifunctional reduced graphene oxide/V2O5 composite hydrogel: fabrication, high
      performance as electromagnetic wave absorbent and supercapacitor.
AB  - Multifunctional graphene hydrogels have attracted great attention aimed at
      practical applications. Herein, the novel and bifunctional composite hydrogel
      containing reduced graphene-oxide nanosheets (RGO) and V2O5 nanobelts (RGO/V2O5)
      is successfully prepared for the first time. Surprisingly, tridimensional (3D)
      RGO/V2O5 composite hydrogels cannot only be used as high-performance
      electromagnetic (EM) wave absorbents; they also exhibit excellent properties
      suitable for supercapacitor electrodes. The composites exhibit a maximum
      absorption of up to -21.5 dB. In particular, a composite hydrogel showed a
      bandwidth of 6.63 GHz, corresponding to a reflection loss at -10 dB, which opens
      the possibility for the use of 3D graphene with other functional nanomaterials as
      lightweight and high-performance EM wave absorption materials. Remarkably, the
      composite hydrogel is capable of delivering a high specific capacitance of about
      320 F g(-1) at a current density of 1.0 A g(-1) .

PMID- 24318770
TI  - A history of pituitary pathology.
AB  - The history of pituitary pathology is a long one that dates back to biblical
      times, but the last 25 years have represented an era of "coming of age." The role
      of the pituitary in health and disease was the subject of many studies over the
      last century. With the development of electron microscopy, immunoassays, and
      immunohistochemistry, the functional alterations associated with pituitary
      disease have been clarified. The additional information provided by molecular
      genetic studies has allowed progress in understanding the pathogenesis of
      pituitary disorders. Nevertheless, many questions remain to be answered. For
      example, pathologists cannot morphologically distinguish locally aggressive
      adenomas from carcinomas when tumor is confined to the sella. Sadly, basal cell
      carcinoma, the most common carcinoma of skin, usually causes less morbidity than
      pituitary adenomas, which occur in almost 20 % of the general population, can
      cause significant illness and even death, and yet are still classified as benign.
      The opportunity to increase awareness of the impact of these common lesions on
      quality of life is the current challenge for physicians and patients. We
      anticipate that ongoing multidisciplinary approaches to pituitary disease
      research will offer new insights into diseases arising from this fascinating
      organ.

PMID- 24318772
TI  - Acute, reproductive toxicity and two-generation teratology studies of a
      standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague
      Dawley rats.
AB  - The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal
      supplements to improve libido and general health amongst the local ethnic
      population. The major quassinoids of E. longifolia improved spermatogenesis and
      fertility but toxicity studies have not been well documented. The reproductive
      toxicity, two generation of foetus teratology and the up-and-down acute toxicity
      were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E.
      longifolia extract (TAF273). The results showed that the median lethal dose (LD50
      ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively.
      Fertility index and litter size of the TAF273 treated were significantly
      increased when compared with those of the non-treated animals. The TAF273-treated
      dams decreased in percentage of pre-implantation loss, post-implantation loss and
      late resorption. No toxic symptoms were observed on the TAF273-treated pregnant
      female rats and their foetuses were normal. The no-observed adverse effect level
      (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in
      rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50
      value. Thus, any human dose derived from converting the rat doses of 100 mg/kg
      and below may be considered as safe for further clinical studies.

PMID- 24318773
TI  - Interventions for the symptoms and signs resulting from jellyfish stings.
AB  - BACKGROUND: Jellyfish envenomations are common amongst temperate coastal regions
      and vary in severity depending on the species. Stings result in a variety of
      symptoms and signs, including pain, dermatological reactions and, in some
      species, Irukandji syndrome (including abdominal/back/chest pain, tachycardia,
      hypertension, sweating, piloerection, agitation and sometimes cardiac
      complications). Many treatments have been suggested for the symptoms and signs of
      jellyfish stings. However, it is unclear which interventions are most effective.
      OBJECTIVES: To determine the benefits and harms associated with the use of any
      intervention, in both adults and children, for the treatment of jellyfish stings,
      as assessed from randomised trials. SEARCH METHODS: We searched the following
      electronic databases in October 2012 and again in October 2013: the Cochrane
      Central Register of Controlled Trials (CENTRAL;The Cochrane Library, Issue 9,
      2013); MEDLINE via Ovid SP (1948 to 22 October 2013); EMBASE via Ovid SP (1980 to
      21 October 2013); and Web of Science (all databases; 1899 to 21 October 2013). We
      also searched reference lists from eligible studies and guidelines, conference
      proceedings and the World Health Organization (WHO) International Clinical Trials
      Registry Platform (ICTRP) and contacted content experts to identify trials.
      SELECTION CRITERIA: We included randomised controlled trials that compared any
      intervention(s) to active and/or non-active controls for the treatment of
      symptoms and signs of jellyfish sting envenomation. No language, publication date
      or publication status restrictions were applied. DATA COLLECTION AND ANALYSIS:
      Two review authors independently conducted study selection and data extraction
      and assessed risk of bias using a standardised form. Disagreements were resolved
      by consensus with a third review author when necessary. MAIN RESULTS: We included
      seven trials with a total of 435 participants. Three trials focused on Physalia
      (Bluebottle) jellyfish, one trial on Carukia jellyfish and three on Carybdea
      alata (Hawaiian box) jellyfish. Two ongoing trials were identified.Six of the
      seven trials were judged as having high risk of bias. Blinding was not feasible
      in four of the included trials because of the nature of the interventions. A wide
      range of interventions were assessed across trials, and a wide range of outcomes
      were measured. We reported results from the two trials for which data were
      available and reported the effects of interventions according to our definition
      of primary or secondary outcomes.Hot water immersion was superior to ice packs in
      achieving clinically significant (at least 50%) pain relief at 10 minutes (one
      trial, 96 participants, risk ratio (RR) 1.66, 95% confidence interval (CI) 1.01
      to 2.72; low-quality evidence) and 20 minutes (one trial, 88 participants, RR
      2.66, 95% CI 1.71 to 4.15; low-quality evidence). No statistically significant
      differences between hot water immersion and ice packs were demonstrated for
      dermatological outcomes.Treatment with vinegar or Adolph's meat tenderizer
      compared with hot water made skin appear worse (one trial, 25 participants, RR
      0.31, 95% CI 0.14 to 0.72; low-quality evidence).Adverse events due to treatment
      were not reported in any trial. AUTHORS' CONCLUSIONS: This review located a small
      number of trials that assessed a variety of different interventions applied in
      different ways and in different settings. Although heat appears to be an
      effective treatment for Physalia (Bluebottle) stings, this evidence is based on a
      single trial of low-quality evidence. It is still unclear what type of
      application, temperature, duration of treatment and type of water (salt or fresh)
      constitute the most effective treatment. In addition, these results may not apply
      to other species of jellyfish with different envenomation characteristics. Future
      research should further assess the most effective interventions using
      standardised research methodology.

PMID- 24318774
TI  - A scoring system to predict the risk of anastomotic leakage after anterior
      resection for rectal cancer.
AB  - BACKGROUND: Various risk factors for anastomotic leakage after anterior resection
      for rectal cancer have been documented in previous studies. However, there have
      been no quantized studies to more accurately predict the risk of anastomotic
      leakage. METHODS: A total of 1,060 patients with rectal cancer who underwent
      anterior resection were included in the study. Potential risk factors for leakage
      including gender, age, body mass index (BMI), diabetes, preoperative
      radiotherapy, tumor size, level of anastomosis, intraoperative blood loss,
      concomitant resection of other organs and TNM stage were subjected to univariate
      analysis. Multivariate logistic regression analysis was used to identify the
      independent risk factors for anastomotic leakage. The scoring system was
      developed based on regression coefficient for each significant risk factor.
      RESULTS: Independent risk factors included male gender, low level of anastomosis
      from anal verge and high-volume intraoperative blood loss. These patients were
      separated into high risk, intermediate risk and low risk groups based on scores
      of 4-5, 2-3, and 0-1. The leakage rates of the three groups were 16.1%, 8.0%, and
      1.9%, respectively (P < 0.001). CONCLUSIONS: The scoring system is effective and
      accurate for identifying a subgroup of patients at high risk for leakage.

PMID- 24318775
TI  - Schizophillum commune causing sinusitis with nasal polyposis in the sub-Himalayan
      region: first case report and review.
AB  - Schizophillum commune is an environmental fungus rarely causing human infections
      of diverse nature. Sinusitis occurs in immunocompromised persons and seldom in
      healthy subjects. Though easily isolated, the lack of awareness of its virulence
      is a bottleneck in the diagnosis of this infection. We report the first case of
      S. commune sinusitis with nasal polyps in an immunocompetent male from the sub
      Himalayan region. The computerized tomography scan findings established the
      clinical diagnosis, and causative agent was confirmed as S. commune. A white,
      woolly mold with septate, hyaline hyphae and characteristic spicules but
      unclamped connections suggested a monokaryotic isolate. Patient was treated
      successfully with fiberoptic endoscopic sinus surgery, and no antifungal therapy
      was instituted. There was no recurrence at review after 1 year.

PMID- 24318777
TI  - Inhibition and induction of barnacle settlement by natural products present in
      octocorals.
AB  - Barnacle settlement inhibitors and inducers are present in the
      gorgonianLeptogorgia virgulata and the pennatulaceanRenilla reniformis. The
      inhibitors are low-molecular-weight compounds (<20,000 daltons) that were
      detected in soft tissue homogenates and dialysates of homogenate and in ambient
      "gorgonian water." Settlement was almost completely inhibited at a dialysate
      concentration of 1.0 g wet weight equivalents/liter. The inhibitors probably
      function in chemical defense against predation and fouling, and could prove
      useful in ship fouling control. The settlement inducers are high-molecular-weight
      substances (>20,000 daltons) that adsorb to surfaces. 

PMID- 24318776
TI  - The intersectionality of discrimination attributes and bullying among youth: an
      applied latent class analysis.
AB  - Discrimination is commonly experienced among adolescents. However, little is
      known about the intersection of multiple attributes of discrimination and
      bullying. We used a latent class analysis (LCA) to illustrate the intersections
      of discrimination attributes and bullying, and to assess the associations of LCA
      membership to depressive symptoms, deliberate self harm and suicidal ideation
      among a sample of ethnically diverse adolescents. The data come from the 2006
      Boston Youth Survey where students were asked whether they had experienced
      discrimination based on four attributes: race/ethnicity, immigration status,
      perceived sexual orientation and weight. They were also asked whether they had
      been bullied or assaulted for these attributes. A total of 965 (78%) students
      contributed to the LCA analytic sample (45% Non-Hispanic Black, 29% Hispanic, 58%
      Female). The LCA revealed that a 4-class solution had adequate relative and
      absolute fit. The 4-classes were characterized as: low discrimination (51%);
      racial discrimination (33%); sexual orientation discrimination (7%); racial and
      weight discrimination with high bullying (intersectional class) (7%). In
      multivariate models, compared to the low discrimination class, individuals in the
      sexual orientation discrimination class and the intersectional class had higher
      odds of engaging in deliberate self-harm. Students in the intersectional class
      also had higher odds of suicidal ideation. All three discrimination latent
      classes had significantly higher depressive symptoms compared to the low
      discrimination class. Multiple attributes of discrimination and bullying co-occur
      among adolescents. Research should consider the co-occurrence of bullying and
      discrimination.

PMID- 24318778
TI  - Isolation, identification, and biological activity of trail-following pheromone
      of termiteTrinervitermes bettonianus (Sjostedt) (Termitidae:Nasutitermitinae).
AB  - The principal compound which posseses trail-following activity at low
      concentration has been isolated from workers and from female alates of the grass
      feeding termiteTrinervitermes bettonianus. Male alates also produce the pheromone
      but in much smaller quantities than the female. The structure of the pheromone
      was determined as the diterpene hydrocarbon cembrene-A from spectra and
      microscale reaction data. 

PMID- 24318779
TI  - House fly oviposition inhibition by larvae ofHermetia illucens, the black soldier
      fly.
AB  - Wild populations of house flies were inhibited from ovipositing into poultry
      manure containing larvae of the black soldier fly,Hermetia illucens (L.). A
      laboratory strain of house fly responded differently, readily ovipositing into
      manure with lower densities of soldier fly larvae, but avoiding the higher
      densities tested. The amount of timeH. illucens larvae occupy the manure prior to
      an oviposition test influences ovipositional responses of house flies. Manure
      conditioned byH. illucens larvae for 4-5 days did not significantly inhibit house
      fly oviposition. We suggest that some type of interspecific chemical
      communication (allomone) is present. 

PMID- 24318780
TI  - Attractive and inhibitory pheromones produced in the bark beetle,Dendroctonus
      brevicomis, during host colonization: Regulation of inter- and intraspecific
      competition.
AB  - Quantities of attractive (exo-brevicomin and frontalin) and inhibitory (trans
      verbenol, verbenone, and ipsdienol) pheromones were monitored in both sexes
      ofDendroctonus brevicomis during their colonization of a ponderosa pine.
      Verbenone was found in males in the greatest amounts at the time of landing, and
      it declined more rapidly than the other pheromones in either sex. The amounts of
      frontalin andexo-brevicomin in males and females, respectively, increased after
      initial boring within the host but began to decline after mating. The quantity
      oftrans-verbenol in both sexes (females had significantly more) declined more
      gradually thanexo-brevicomin, frontalin, and verbenone. Ipsdienol was found only
      in males during the initial stages of attack when encountering the resin. It is
      suggested that along with a general decline in all pheromonal components, a
      sufficient change in the ratio of the attractive pheromones to an inhibitory
      pheromone,trans-verbenol, may play a role in termination of aggregation.trans
      Verbenol may also function along with verbenone and ipsdienol in limiting the
      density of attack and thus intraspecific competition. These inhibitory pheromones
      also appear to cause several competing species of bark beetle to avoid landing in
      areas infested withD. brevicomis, even when their own pheromone is present. 

PMID- 24318781
TI  - Chemosensitivity of lobster,Homarus americanus, to secondary plant compounds:
      Unused receptor capabilities.
AB  - Chemosensitivity to secondary plant substances was examined
      electrophysiologically and behaviorally for the lobsterHomarus americanus.
      Neurophysiological experiments show that some chemoreceptor cells in the
      antennules (representing the sense of smell) and walking legs (representing the
      sense of taste) were excited by secondary compounds from plants of marine and
      terrestrial origin. These compounds include amygdalin, atropine sulfate,
      bromoform, caffeine,p-coumaric acid, diiodomethane, ferulic acid, heliotropin,
      phloroglucinol, quinine sulfate, salicin, sinigrin, tannic acid, and tomatine.
      The possible behavioral function of three of these compounds was tested.
      Phloroglucinol and ferulic acid had no observable effect on any aspect of feeding
      behavior at any concentration tested. Tannic acid, which is related to
      polyphenols found in marine algae, had no observable effect at any concentration
      tested on orientation to and grasping of food (activities controlled primarily by
      antennular and leg chemoreceptors, respectively) but did have an inhibitory
      effect on food ingestion (an activity controlled primarily by mouthpart
      chemoreceptors). These electrophysiological and behavioral results suggest that
      potential chemoreceptive information derived from many secondary plant compounds
      may not be used in feeding behavior. The receptors sensitive to these compounds
      may represent a "common chemical sense" as suggested by Dethier (1980). However,
      at least one compound, tannic acid, that is smelled and tasted by lobsters can
      function as a feeding inhibitor at the level of the mouthparts. 

PMID- 24318782
TI  - Fate of photosensitizing furanocoumarins in tolerant and sensitive insects.
AB  - The fate of [(14)C]xanthotoxin (8-methoxypsoralen) was studied in larvae of
      insect species that are tolerant (Papilio polyxenes Stoll) or sensitive
      (Spodoptera frugiperda J.E. Smith) to the phototoxic effects of photosensitizing
      psoralens. Both insects metabolize xanthotoxin by oxidative cleavage of the furan
      ring, but the detoxification occurs at a much more rapid rate inP. polyxenes in
      which >95% of an oral 5 MUg/g xanthotoxin dose is metabolized within 1.5 hr after
      treatment. The detoxification of psoralens byP. polyxenes appears to occur
      primarily in the midgut tissue prior to absorption, with the result that the
      intact phototoxin does not reach appreciable levels in body tissues. Studies with
      an angular furanocoumarin indicated that isopsoralens are metabolized byP.
      polyxenes at a somewhat slower rate than observed for psoralens; however, a
      reduced rate of metabolic detoxification of isopsoralens probably does not
      explain the fact that psoralen tolerance inP. polyxenes does not extend to the
      isopsoralen series. 

PMID- 24318783
TI  - Characterization of a sex pheromone in the blue crab,Callinectes sapidus:
      Crustecdysone studies.
AB  - The molting hormone/sex pheromone hypothesis of Kittredge and Takahashi (1972)
      and Kittredge et al. (1971) was explored inC. sapidus. Two concentrations of
      crustecdysone (5 * 10(-5) M and 5 * 10(-6) M) were presented to male crabs in a
      bioassay system in which courtship behavior was monitored. The results
      demonstrate that crustecdysone does not stimulate courtship in this species. The
      physical properties of crustecdysone were also compared to those of the partially
      purified sex pheromone derived from pubescent females. Using HPLC and mass
      spectral analysis, no correspondence of crustecdysone with the bioactive material
      could be shown. These results, in conjunction with the findings of others, do not
      support an evolutionary relationship between the molting hormone and sex
      pheromone communication in the Crustacea. 

PMID- 24318784
TI  - Woodmice (Apodemus sylvaticus) can distinguish conspecific from heterospecific
      odors in the field.
AB  - In order to eliminate a common source of bias from trap-choice experiments in the
      field, trapping data from a study on the olfactory biology of the woodmouse were
      screened, and only those in which a direct choice existed were analyzed further.
      Woodmice choose conspecific odor to no odor but make no distinction between
      heterospecific odor and no odor. When choosing between conspecific and
      heterospecific odors, a significant majority choose conspecific. 

PMID- 24318785
TI  - Extreme intraspecific chemical variability in soldier defense secretions of
      allopatric and sympatric colonies ofLongipeditermes longipes.
AB  - The chemical defense secretions of major and minor soldiers of over 18 colonies
      of the primitive glue-squirting nasute termiteLongipeditermes longipes (Isoptera,
      Termitidae, Nasutitermitinae) were analyzed chormatographically. The colonies,
      collected from four rainforest sites in peninsular Malaysia, showed monoterpene
      patterns rich in pinenes and limonene but with few quantitative differences
      between colonies. In marked contrast, the diterpene chemistry is high variable,
      and includes tricyclic (trinervitane), tetracyclic (rippertane), bicyclic
      (secotrinervitane), and a new spirotetracyclic (longipane) skeleton. Three new
      natural products are included in this remarkable and unprecedented example of
      structural diversity among different colonies of a single species. 

PMID- 24318786
TI  - Metabolism of uscharidin, a milkweed cardenolide, by tissue homogenates of
      monarch butterfly larvae,Danaus plexippus L.
AB  - Midgut and fat body homogenates of monarch butterfly larvae,Danaus plexippus L.
      (Lepidoptera:Danaidae), were examined for microsomal monooxygenase activity
      usingp-chloro-N-methylanilineN-demethylation and for the ability to metabolize a
      milkweed (Asclepias spp.) cardenolide (C23 steroid glycoside), uscharidin. All
      homogenates tested had bothN-demethylation and uscharidin biotransformation
      activities. Both transformations required NADPH. The monooxygenase inhibitors
      sesamex, SKF525A, and carbon monoxide inhibitedN-demethylation but not uscharidin
      biotransformation. Subsequent subcellular fractionation revealed the uscharidin
      biotransformation occurs in the soluble fraction and not the microsomal fraction,
      whileN-demethylation occurs in the microsomal fraction and not the soluble
      fraction. The larval NADPH-dependent microsomal monooxygenase apparently is not
      involved in the metabolism of uscharidin. 

PMID- 24318787
TI  - Chemical induction of feeding in California spiny lobster,Panulirus interruptus
      (Randall): : Responses to molecular weight fractions of abalone.
AB  - Molecular weight fractions of abalone muscle were tested for the ability to
      induce appetitive feeding and locomotor behavior in the spiny lobster,Panulirus
      interruptus. Fractions of <1000, 1000-10,000 and >10,000 daltons were isolated by
      ultrafiltrations and gel chromatography from a seawater extract of abalone
      muscle. The two lower-molecular-weight fractions (<1000, 1000-10,000) were the
      least stimulatory of the three fractions tested, and both were ineffective as
      feeding stimulants. Solutions combining any two of the three isolated fractions
      produced behavioral activity equal to that caused by whole extract; thus, no
      single fraction was essential to the stimulatory capacity of abalone. The >1000
      dalton fraction was also highly stimulatory, meaning that large and not small
      molecules were essential in initiating feeding. Finally, a 75% ethanol-insoluble
      component of the <10,000 fraction was effective, while the ethanol-soluble
      portion was not. Since the insoluble material consisted predominantly of peptides
      and polypeptides, it is probable that these molecules act as principal stimulants
      in abalone muscle. 

PMID- 24318789
TI  - Skin and diabetes mellitus: what do we know?
AB  - Diabetes mellitus (DM) is becoming increasingly prevalent worldwide. Although
      major complications of this condition involve kidney, retina and peripheral
      nerves, the skin of diabetic patients is also frequently injured. Hence, interest
      is mounting in the definition of the structural and molecular profile of non
      complicated diabetic skin, i.e., before injuries occur. Most of the available
      knowledge in this area has been obtained relatively recently and, in part,
      derives from various diabetic animal models. These include both insulin-dependent
      and insulin-resistant models. Structural work in human diabetic skin has also
      been carried out by means of tissue samples or of non-invasive methods.
      Indications have indeed been found for molecular/structural changes in diabetic
      skin. However, the overall picture that emerges is heterogeneous, incomplete and
      often contradictory and many questions remain unanswered. This review aims to
      detail, as much as possible, the various pieces of current knowledge in a
      systematic and synoptic manner. This should aid the identification of areas in
      which key questions are still open and more research is needed. A comprehensive
      understanding of this field could help in determining molecular targets for the
      prevention and treatment of skin injuries in DM and markers for the monitoring of
      cutaneous and systemic aspects of the disease. Additionally, with the increasing
      development of non-invasive optics-based deep-tissue-imaging diagnostic
      technologies, precise knowledge of cutaneous texture and molecular structure
      becomes an important pre-requisite for the use of such methods in diabetic
      patients. 

PMID- 24318788
TI  - Time course and dimensions of postural control changes following neuromuscular
      training in youth field hockey athletes.
AB  - PURPOSE: Injury prevention effects of neuromuscular training have been partly
      attributed to postural control adaptations. Uncertainty exists regarding the
      magnitude of these adaptations and on how they can be adequately monitored. The
      objective was to determine the time course of neuromuscular training effects on
      functional, dynamic and static balance measures. METHODS: Thirty youth (14.9 +/-
      3 years) field hockey athletes were randomised to an intervention or control
      group. The intervention included a 20-min neuromuscular warm-up program performed
      twice weekly for 10 weeks. Balance assessments were performed at baseline, week
      three, week six and post-intervention. They included the star excursion balance
      test (SEBT), balance error scoring system (BESS), jump-landing time to
      stabilization (TTS) and center of pressure (COP) sway velocity during single-leg
      standing. RESULTS: No baseline differences were found between groups in
      demographic data and balance measures. Adherence was at 86%. All balance measures
      except the medial-lateral TTS improved significantly over time (p < 0.05) in both
      groups. Significant group by time interactions were found for the BESS score (p <
      0.001). The intervention group showed greater improvements (69.3 +/- 10.3%) after
      10 weeks in comparison to controls (31.8 +/- 22.1%). There were no significant
      group by time interactions in the SEBT, TTS and COP sway velocity. CONCLUSIONS:
      Neuromuscular training was effective in improving postural control in youth team
      athletes. However, this effect was not reflected in all balance measures
      suggesting that the neuromuscular training did not influence all dimensions of
      postural control. Further studies are needed to confirm the potential of specific
      warm-up programs to improve postural control.

PMID- 24318790
TI  - A giant coronary artery aneurysm with a fistula followed-up for 12 years using
      the contrast-enhanced computed tomography scan.
AB  - We report a case of a 35-year-old woman who was diagnosed with a giant coronary
      artery aneurysm (CAA) with a fistula and followed-up using the contrast-enhanced
      computed tomography scan and 2-dimensional transthoracic echocardiography. The
      diameter and volume cubic content of the giant CAA had increased linearly during
      the 12-year follow-up period without any complications. As there are few reports
      about long-term follow-up of giant CAAs without a surgical intervention, the
      natural course of a giant CAA is still unclear. Thus, we may need to closely
      follow-up chronological changes of a giant CAA to decide the treatment strategy. 

PMID- 24318791
TI  - Utility of a scoring balloon for a severely calcified lesion: bench test and
      finite element analysis.
AB  - We aimed to investigate the effectiveness of a scoring balloon catheter in
      expanding a circumferentially calcified lesion compared to a conventional balloon
      catheter using an in vitro experiment setting and elucidate the underlying
      mechanisms of this ability using a finite element analysis. True efficacy of the
      scoring device and the underlying mechanisms for heavily calcified coronary
      lesions are unclear. We employed a Scoreflex scoring balloon catheter
      (OrbusNeich, Hong Kong, China). The ability of Scoreflex to dilate a calcified
      lesion was compared with a conventional balloon catheter using 3 different sized
      calcium tubes. The thickness of the calcium tubes were 2.0, 2.25, and 2.5 mm. The
      primary endpoints were the successful induction of cracks in the calcium tubes
      and the inflation pressures required for inducing cracks. The inflation pressure
      required for cracking the calcium tubes were consistently lower with Scoreflex (p
      < 0.05, Student t test). The finite element analysis revealed that the first
      principal stress applied to the calcified plaque was higher by at least threefold
      when applying the balloon catheter with scoring elements. A scoring balloon
      catheter can expand a calcified lesion with lower pressure than that of a
      conventional balloon. The finite element analysis revealed that the concentration
      of the stress observed in the outside of the calcified plaque just opposite to
      the scoring element is the underlying mechanism of the increased ability of
      Scoreflex to dilate the calcified lesion.

PMID- 24318792
TI  - Interaction of the FAF B-containing subunit with the Photosystem 1 core
      heterodimer.
AB  - The structure of the predicted amino acid sequence in the FX domain of
      Photosystem 1 was studied by molecular modeling and a working hypothesis was
      developed for the functional interaction of PsaC with the core heterodimer. We
      propose that the intervening sequences between homologous cysteines in the FX
      cluster form two flexible loops and participate in the binding of PsaC, and that
      the arginine residues in the two surface-exposed loops may promote the
      interaction between the P700-FX core and the subunit. The model was tested
      experimentally; chemical modification of arginine residues in the P700-FX core
      using phenylglyoxal prevented reconstitution of the core with PsaC and PsaD after
      insertion of FeS clusters in vitro. Treatment of the P700-FX core with trypsin
      also prevented reconstitution of terminal electron transfer to FAFB, although
      neither treatments affected the electron transfer to FX as judged by flash
      kinetic spectrophotometry. Electron transfer in the P700-FAFB complex was not
      impaired by either phenylglyoxal or trypsin treatment indicating that the small
      subunit(s) protect the arginine residues that become chemically modified or
      cleaved. The data are consistent with the working model and point to additional
      experiments designed to identify the specific residues involved in the
      interaction between the P700-FX core and PsaC. 

PMID- 24318793
TI  - Selective extraction of 22 kDa and 10 kDa polypeptides from Photosystem II
      without removal of 23 kDa and 17 kDa extrinsic proteins.
AB  - Selective solubilization of Photosystem II membranes with the non-ionic detergent
      octyl thioglucopyranoside has allowed the isolation of a PS II system which has
      been depleted of the 22 and 10 kDa polypeptides but retains all three extrinsic
      proteins (33, 23 and 17 kDa). The PS II membranes which have been depleted of the
      22 and 10 kDa species show high rates of oxygen evolution activity, external
      calcium is not required for activity and the manganese complex is not destroyed
      by exogenous reductants. When we compared this system to control PS II membranes,
      we observed a minor modification of the reducing side, and a conversion of the
      high-potential to the low-potential form of cytochrome b 559. 

PMID- 24318794
TI  - The effect of UV-B radiation on photosynthesis and respiration of phytoplankton,
      benthic macroalgae and seagrasses.
AB  - Several species of marine benthic algae, four species of phytoplankton and two
      species of seagrass have been subjected to ultraviolet B irradiation for varying
      lengths of time and the effects on respiration, photosynthesis and fluorescence
      rise kinetics studied. No effect on respiration was found. Photosynthesis was
      inhibited to a variable degree in all groups of plants after irradiation over
      periods of up to 1 h and variable fluorescence was also inhibited in a similar
      way. The most sensitive plants were phytoplankton and deep-water benthic algae.
      Intertidal benthic algae were the least sensitive to UV-B irradiation and this
      may be related to adaptation, through the accumulation of UV-B screening
      compounds, to high light/high UV-B levels. Inhibition of variable fluorescence
      (Fv) of the fluorescence rise curve was a fast and sensitive indicator of UV-B
      damage. Two plants studied, a brown alga and a seagrass, showed very poor
      recovery of Fv over a period of 32 h. 

PMID- 24318795
TI  - Compared thermoluminescence characteristics of pea thylakoids studied in vitro
      and in situ (in leaves). The effect of photoinhibitory treatments.
AB  - Characteristics of thermoluminescence (TL) glow curves were studied in thylakoids
      (isolated from pea leaves) or in intact pea leaves after an exposure to very high
      light for 2 min in the TL device. The inhibition of photosynthesis was detected
      as decreases of oxygen evolution rates and/or of variable fluorescence.In
      thylakoids exposed to high light, then dark adapted for 5 min, a flash regime
      induced TL glow curves which can be interpreted as corresponding to special B
      bands since: 1) they can be fitted by a single B band (leaving a residual band at
      -5 degrees C) with a lower activation energy and a shift of the peak maximum by 
      5 to -6 degrees C and, 2) the pattern of oscillation of their amplitudes was
      normal with a period of 4 and maxima on flashes 2 and 6. During a 1 h dark
      adaptation, no recovery of PS II activity occurred but the shift of the peak
      maximum was decreased to -1 to -2 degrees C, while the activation energy of B
      bands increased. It is supposed that centers which remained active after the
      photoinhibitory treatment were subjected to reversible and probably
      conformational changes.Conversely, in intact leaves exposed to high light and
      kept only some minutes in the dark, TL bands induced by a flash regime were
      composite and could be deconvoluted into a special B band peaking near 30 degrees
      C and a complex band with maximum at 2-5 degrees C. In the case of charging bands
      by one flash, this low temperature band was largely decreased in size after a 10
      min dark adaptation period; parallely, an increase of the B band type component
      appeared. Whatever was the flash number, bands at 2-5 degrees C were suppressed
      by a short far red illumination given during the dark adaptation period and only
      remained a main band a 20 degrees C; therefore, the origin of the low temperature
      band was tentatively ascribed to recombinations in centers blocked in state S2QA
      (-)QB (2-). In vivo, the recovery of a moderately reduced state in the PQ pool,
      after an illumination, would be slow and under the dependence of a poising
      mechanism, probably involving an electron transfer between cytosol and
      chloroplasts or the so-called 'chlororespiration' process. 

PMID- 24318796
TI  - The role of CP 47 in the evolution of oxygen and the binding of the extrinsic 33
      kDa protein to the core complex of Photosystem II as determined by limited
      proteolysis.
AB  - In order to identify the domain within Photosystem II complexes that functions in
      the evolution of oxygen, we performed limited proteolysis with lysylendopeptidase
      of the core complex of Photosystem II which had been depleted of the extrinsic 33
      kDa protein (Mn-stabilizing protein). The cleavage sites were estimated from the
      amino-terminal sequences of the degradation fragments, their apparent molecular
      masses and amino-acid compositions. Under certain conditions, the D2 protein was
      cleaved at Lys13; and a chlorophyll a-binding protein, CP 47, was cleaved at
      Lys227 and Lys389. Another chlorophyll a-binding protein, CP 43, was degraded
      more rapidly than CP 47. The oxygen-evolving activity and the capacity for
      rebinding of the 33-kDa protein to the core complex of Photosystem II decreased
      in parallel, with kinetics very similar to those of the cleavage of CP 47 at
      Lys389. These observations strongly suggest that the hydrophilic domain around
      Lys389 of CP 47, which are located on the lumenal side, is important in the
      binding of the 33-kDa protein and in maintaining the oxygen-evolving activity of
      the Photosystem II complex. 

PMID- 24318797
TI  - Photosynthetic reaction center mutagenesis via chimeric rescue of a non
      functional Rhodobacter capsulatus puf operon with sequences from Rhodobacter
      sphaeroides.
AB  - Photosynthetically active chimeric reaction centers which utilize genetic
      information from both Rhodobacter capsulatus and Rb. sphaeroides puf operons were
      isolated using a novel method termed chimeric rescue. This method involves in
      vivo recombination repair of a Rb. capsulatus host operon harboring a deletion in
      pufM with a non-expressed Rb. sphaeroides donor puf operon. Following
      photosynthetic selection, three revertant classes were recovered: 1) those which
      used Rb. sphaeroides donor sequence to repair the Rb. capsulatus host operon
      without modification of Rb. sphaeroides puf operon sequences (conversions), 2)
      those which exchanged sequence between the two operons (inversions), and 3) those
      which modified plasmid or genomic sequences allowing expression of the Rb.
      sphaeroides donor operon. The distribution of recombination events across the Rb.
      capsulatus puf operon was decidedly non-random and could be the result of the
      intrinsic recombination systems or could be a reflection of some species
      specific, functionally distinct characteristic(s). The minimum region required
      for chimeric rescue is the D-helix and half of the D/E-interhelix of M. When puf
      operon sequences 3' of nucleotide M882 are exchanged, significant impairment of
      excitation trapping is observed. This region includes both the 3' end of pufM and
      sequences past the end of pufM. 

PMID- 24318798
TI  - Flash-induced reduction of cytochrome b-559 by Q infB (sup-) in chloroplasts in
      the presence of protonophores.
AB  - Flash-induced, fast (t 1/2 ~ 1 ms), reversible reduction of the high potential
      cytochrome b-559 (cyt b-559HP) was observed in chloroplasts in the presence of 2
      MUM protonophore, FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone), CCCP
      (carbonylcyanide 3-chlorophenylhydrazone) or SF 6847 (2,6-di-(t-butyl)-4-(2',2'
      dicyanovinyl)phenol). These protonophores promote autooxidation of cyt b-559HP in
      the dark (Arnon and Tang 1988, Proc Natl Acad Sci USA 85: 9524). No fast
      photoreduction could, however, be observed if the molecules were oxidized with
      ferricyanide in the absence of protonophores. This suggests that the molecules
      must be deprotonated to be capable for fast photoreduction.Photoreduction of cyt
      b-559HP was largely insensitive to DBMIB (2,5-dibromo-3-methyl-6-isopropyl-p
      benzoquinone), but was inhibited by DCMU (3-(3,4-dichlorophenyl)-1,1
      dimethylurea). With a train of flashes, no oscillation could be observed in the
      amplitudes of photoreduction. These data strongly suggest that cyt b-559HP is
      reduced by the semireduced secondary quinone acceptor (QB (-)) of Photosystem 2. 

PMID- 24318799
TI  - PAM fluorometer based on medium-frequency pulsed Xe-flash measuring light: A
      highly sensitive new tool in basic and applied photosynthesis research.
AB  - A newly developed modulation fluorometer is described which employs repetitive 1
      MUs Xe-flashes for excitation light. Similar to the standard PAM Chlorophyll
      Fluorometer, which uses 1 MUs LED pulses for measuring light, the integrated
      measuring light intensity is sufficiently low to monitor the dark-fluorescence
      level, Fo. The maximal fluorescence yield, Fm, can be determined with high
      selectivity upon application of a saturating light pulse. The Xe-PAM displays
      exceptionally high sensitivity, enabling quenching analysis at chlorophyll
      concentrations as low as 1 MUg/l, thus allowing to assess photosynthesis of
      phytoplankton in natural waters like lakes, rivers and oceans. Due to high
      flexibility in the choice of excitation and emission wavelengths, this system
      also provides the experimental basis for a thorough study of fluorescence and
      photosynthesis properties of various algae classes with differing antenna
      organisation. By appropriate modifications, the instrument may as well be used to
      measure with great sensitivity and selectivity other types of fluorescence (e.g.
      NADPH-fluorescence), as well as light-scattering and absorbance changes. 

PMID- 24318800
TI  - Retirement patterns and the macroeconomy, 1992-2010: the prevalence and
      determinants of bridge jobs, phased retirement, and reentry among three recent
      cohorts of older americans.
AB  - PURPOSE OF THE STUDY: Older Americans contemplating retirement today face a very
      different economic environment than prior cohorts did. This article examines
      whether the retirement patterns of older Americans have changed as a result.
      DESIGN AND METHODS: Using data from 10 waves of the Health and Retirement Study
      (HRS), we examine the prevalence of bridge jobs, phased retirement, and labor
      market reentry among 3 recent cohorts of older Americans, from 1992 through 2010.
      Determinants of retirement transitions are examined using bivariate comparisons
      and multivariate logistic and multinomial logistic regression models. RESULTS: We
      find that traditional one-time, permanent exits from the labor force continue to
      be the exception rather than the rule and that the retirement patterns of the
      Early Boomers, those on the cusp of retirement during the recent Great Recession,
      appear to be diverging from those of earlier cohorts. The Early Boomer women, in
      particular, were more likely than those in previous cohorts, the HRS Core and the
      HRS War Babies, to move to a bridge job prior to exiting the labor force
      completely and both Early Boomer men and women were more likely to leave their
      career jobs involuntarily, with layoffs being a key factor. IMPLICATIONS: The "do
      it-yourself" approach to retirement planning-with individuals managing a large
      portion of their retirement finances-is now common among older Americans. This
      change in the retirement environment, combined with a significant and persistent
      cyclical downturn, may have long-lasting effects and suggests that the concept of
      retirement in the United States will continue to evolve.

PMID- 24318801
TI  - Radiating disparity in IBD.

PMID- 24318802
TI  - De novo membrano-proliferative nephritis following interferon therapy for chronic
      hepatitis C (case study and literature review).

PMID- 24318803
TI  - Sivelestat sodium hydrate inhibits neutrophil migration to the vessel wall and
      suppresses hepatic ischemia-reperfusion injury.
AB  - BACKGROUND: Sivelestat sodium hydrate (sivelestat) is a specific neutrophil
      elastase inhibitor that is effective in treating acute lung injury associated
      with systemic inflammatory response syndrome. As such, it may be useful in
      treating hepatic ischemia-reperfusion injury (IRI), a condition in which
      neutrophils transmigrate into the interstitium, leading to release of neutrophil
      elastase from neutrophils and consequent damage to the affected tissue,
      particularly in cases of hepatic failure after liver transplantation or massive
      liver resection. AIMS: The purpose of this study was to examine whether treatment
      with sivelestat inhibits neutrophil adhesion and migration to the vessel wall and
      suppresses hepatic IRI. METHODS: Whether and, if so, the extent to which
      sivelestat suppresses the adhesion and migration of neutrophils and reduces liver
      damage in hepatic IRI was examined in a human umbilical vein endothelial cell
      (HUVEC) model and a rat hepatic IRI model. RESULTS: In the HUVEC model, the
      extent of the adhesion and migration of neutrophils stimulated by platelet
      activating factor were found to be dose-dependently inhibited by sivelestat
      treatment (p < 0.05). In the rat model, serum liver enzyme levels were
      significantly lower at 12 h after reperfusion, and the number of neutrophils that
      had migrated to extravascular sites was significantly less in the treatment group
      compared to the control group (p < 0.05). CONCLUSION: Sivelestat inhibits the
      adhesion and migration of neutrophils to vascular endothelium in hepatic IRI,
      thereby suppressing liver injury.

PMID- 24318804
TI  - Impact of pre-existing type-2 diabetes on patient outcomes after radical
      resection for gastric cancer: a retrospective cohort study.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of pre-existing type
      2 diabetes on postoperative recovery and prognosis in gastric cancer (GC)
      patients who underwent radical gastrectomy. RESEARCH DESIGN AND METHODS: From
      June 2001 to June 2011, a total of 1,014 eligible patients were enrolled. Among
      them, 67 patients were diagnosed with type-2 diabetes. The clinicopathologic
      features and prognostic data were compared between patients with type-2 diabetes
      (the DM group) and without diabetes (the non-DM group). RESULTS: Median survival
      was 68.3 months. The 5-year overall survival in the DM group was similar to that
      in the non-DM group (52.1 vs. 53.0 %, p = 0.411). Propensity score matching
      analysis demonstrated that the hazard ratio of death in the DM group was 1.191
      (95 % confidential index 0.693-2.072; p = 0.531) compared to the-non DM group.
      Incidence of postoperative complications was higher in the DM group than in the
      non-DM group (17.9 vs. 8.1 %, p = 0.006). The DM remission rate was 46 % among
      patients who received Roux-en-Y reconstruction, and 13 % among patients who
      received Billroth II anastomosis (p = 0.009). The 5-year overall survival rate
      was 62.1 % for patients with cured or improved DM and 23.4 % for patients with
      worse or same DM status (p = 0.003). CONCLUSION: Type-2 diabetes can be cured by
      radical gastrectomy plus Roux-en-Y reconstruction in some GC patients. Pre
      existing diabetes is associated with increased postoperative complications and
      decreased survival when it becomes worse after curative dissection for GC.

PMID- 24318805
TI  - Epigallocatechin gallate does not accelerate the early phase of liver
      regeneration after partial hepatectomy in rats.
AB  - BACKGROUND: Two-thirds partial hepatectomy (PHx) is an established model for the
      study of liver regeneration after resection. This process is accompanied by
      oxidative stress. AIMS: In our study, we tested the effect of epigallocatechin
      gallate (EGCG), a green tea antioxidant, on the early phase of liver regeneration
      after PHx. METHODS: Male Wistar rats were divided into five groups: (I)
      laparotomy + water for intraperitoneal injections, (II) laparotomy + EGCG 50
      mg/kg body weight, (III) PHx + water for injections, (IV) PHx + EGCG 20 mg/kg and
      (V) PHx + EGCG 50 mg/kg, for 3 consecutive days. The rats were killed 24 h after
      surgery. Biochemical analysis of rat sera was performed. Histological samples
      were stained with hematoxylin & eosin and bromodeoxyuridine (BrdU). In
      hepatectomized rats, we also measured plasma malondialdehyde, tissue
      malondialdehyde, glutathione and cytokines levels, the activity of caspases 3/7,
      expression of Nqo-1 and HO-1 genes at the mRNA level, and expression of p21, p
      p27 and p-p53 genes at the protein level. RESULTS: We observed lower accumulation
      of BrdU in group V when compared to groups III and IV. The activity of caspases
      3/7 and expression of p-p53 were lower in group V than in groups III and IV.
      Tissue levels of IL-6 were lower in group V when compared to group III.
      Significant differences were not noted in other parameters. CONCLUSIONS:
      Administration of EGCG did not stimulate early phase liver regeneration in rats
      after PHx. There was even lower DNA synthesis in the group treated with a high
      dose of EGCG.

PMID- 24318806
TI  - Different peptic ulcer bleeding risk in chronic kidney disease and end-stage
      renal disease patients receiving different dialysis.
AB  - BACKGROUND: End stage renal disease (ESRD) patients receiving hemodialysis (HD)
      have a higher risk of peptic ulcer bleeding (PUB). AIMS: Whether ESRD patients
      receiving peritoneal dialysis (PD) also carries a higher risk of PUB has not been
      studied. METHODS: This was a cohort study using Taiwan's National Health
      Insurance research database, whereby 11,408 patients, including 2,239 PD, 2,328
      HD, 2,267 chronic kidney disease (CKD) and 4,574 controls with age-sex matching
      were recruited. The log-rank test was used to analyze differences in accumulated
      PUB-free survival rates between groups. Cox proportional hazard regression was
      performed to evaluate independent risk factors for PUB in all the enrollees.
      RESULTS: During the 7-year follow-up, PD and CKD patients had a significantly
      higher rate of PUB than matched controls. The risk of PUB between PD and CKD was
      not significantly different. Moreover, patients receiving HD carried a higher
      risk of PUB than those receiving PD, with CKD and controls (p all <0.05, by log
      rank test). Cox proportional hazard regression analysis showed that CKD (HR 3.99,
      95 % CI 2.24-7.13), PD (HR 3.71, 95 % CI 2.00-6.87) and HD (HR 11.96, 95 % CI
      7.04-20.31) were independently associated with an increased risk of PUB. Being
      elderly, male, having hypertension, diabetes, cirrhosis, and nonsteroidal anti
      inflammatory drugs and steroid use were other independent risk factors of PUB in
      all enrollees. CONCLUSIONS: Patients with CKD and ESRD receiving PD or HD carried
      a higher risk for PUB. They should be screened for risk factors for PUB and
      receive some protective measures to prevent PUB.

PMID- 24318807
TI  - BMI-for-age Z-score distribution shifts among Chinese children: gender disparity.
AB  - OBJECTIVE: To identify gender differences among Chinese school-aged children from
      1995 to 2010, and to project the future BMI-for-age Z-score distribution and
      prevalence of obesity. METHODS: The data were from four cross-sectional surveys
      (1995, 2000, 2005, and 2010) of Chinese National Surveys on Students Constitution
      and Health (CNSSCH) with a national representative sample of Chinese children,
      involving more than 200,000 participants at each survey. BMI-for-age Z-score
      distributional shifts overall and in percentiles were compared by gender. Average
      shift was calculated for four survey periods and used for projecting future
      distributions and obesity prevalence. RESULTS: BMI-for-age Z-score increased more
      in their upper percentile distribution, indicating that Chinese children have
      become heavier over the past 15 years. Gender disparity in BMI-for-age Z-score
      has become wider during the period. Over a 15-year period, BMI-for-age Z-score
      shift among girls has been stable, while boy's BMI-for-age Z-score shifts has
      increased linearly. By 2020, the obesity prevalence is predicted to be 10.18% and
      4.99% for boys and girls, respectively. CONCLUSIONS: The wider gender disparity
      suggested a larger proportion of obesity in boys than in girls. Therefore, gender
      specific preventive guidelines and public health policies for childhood obesity
      and cardiovascular diseases are urgently needed in China.

PMID- 24318808
TI  - The role of oxidative stress in citreoviridin-induced DNA damage in human liver
      derived HepG2 cells.
AB  - We hypothesize that citreoviridin (CIT) induces DNA damage in human liver-derived
      HepG2 cells through an oxidative stress mechanism and that N-acetyl-l-cysteine
      (NAC) protects against CIT-induced DNA damage in HepG2 cells. CIT-induced DNA
      damage in HepG2 cells was evaluated by alkaline single-cell gel electrophoresis
      assay. To elucidate the genotoxicity mechanisms, the level of oxidative DNA
      damage was tested by immunoperoxidase staining for 8-hydroxydeoxyguanosine (8
      OHdG); the intracellular generation of reactive oxygen species (ROS) and reduced
      glutathione (GSH) were examined; mitochondrial membrane potential and lysosomal
      membranes' permeability were detected; furthermore, protective effects of NAC on
      CIT-induced ROS formation and CIT-induced DNA damage were evaluated in HepG2
      cells. A significant dose-dependent increment in DNA migration was observed at
      tested concentrations (2.50-10.00 uM) of CIT. The levels of ROS, 8-OHdG formation
      were increased by CIT, and significant depletion of GSH in HepG2 cells was
      induced by CIT. Destabilization of lysosome and mitochondria was also observed in
      cells treated with CIT. In addition, NAC significantly decreased CIT-induced ROS
      formation and CIT-induced DNA damage in HepG2 cells. The data indicate that CIT
      induces DNA damage in HepG2 cells, most likely through oxidative stress
      mechanisms; that NAC protects against DNA damage induced by CIT in HepG2 cells;
      and that depolarization of mitochondria and lysosomal protease leakage may play a
      role in CIT-induced DNA damage in HepG2 cells.

PMID- 24318809
TI  - MRI of neonatal necrotizing enterocolitis in a rodent model.
AB  - Neonatal necrotizing enterocolitis (NEC) is a poorly understood life-threatening
      illness afflicting premature infants. Research is hampered by the absence of a
      suitable method to monitor disease progression noninvasively. The primary goal of
      this research was to test in vivo MRI methods for the noninvasive early detection
      and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal
      rats were delivered by cesarean section at embryonic stage of day 20 after the
      beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial
      colonization to induce NEC. Naturally born and dam-fed neonatal rats were used as
      healthy controls. In vivo MRI studies were performed using a Bruker 9.4-T scanner
      to obtain high-resolution anatomical MR images using both gradient echo and spin
      echo sequences, pixel-by-pixel T2 maps using a multi-slice-multi-echo sequence,
      and maps of the apparent diffusion coefficient (ADC) of water using a spin echo
      sequence, to assess the degree of ileal damage. Pups were sacrificed at the end
      of the MRI experiment on day 2 or 4 for histology. T2 measured by MRI was
      increased significantly in the ileal regions of pups with NEC by histology (106.3
      +/- 6.1 ms) compared with experimentally stressed pups without NEC (85.2 +/- 6.8
      ms) and nonstressed, control rat pups (64.9 +/- 2.3 ms). ADC values measured by
      diffusion-weighted MRI were also increased in the ileal regions of pups with NEC
      by histology [(1.98 +/- 0.15) * 10(-3) mm(2)/s] compared with experimentally
      stressed pups without NEC [(1.43 +/- 0.16) * 10(-3) mm(2)/s] and nonstressed
      control pups [(1.10 +/- 0.06) * 10(-3) mm(2)/s]. Both T2 and ADC values between
      these groups were found to be significantly different (p < 0.03). The correlation
      of MRI results with histologic images of the excised ileal tissue samples
      strongly suggests that MRI can noninvasively identify NEC and assess intestinal
      injury prior to clinical symptoms in a physiologic rat pup model of NEC.

PMID- 24318810
TI  - In situ hybridization methods for mouse whole mounts and tissue sections with and
      without additional beta-galactosidase staining.
AB  - In situ hybridization is a powerful method for detecting endogenous mRNA
      sequences in morphologically preserved samples. We provide in situ hybridization
      methods, which are specifically optimized for mouse embryonic samples as whole
      mounts and section tissues. Additionally, beta-Galactosidase (beta-gal) is a
      popular reporter for detecting the expression of endogenous or exogenous genes.
      We reveal that 6-chloro-3-indoxyl-beta-D-galactopyranoside (S-gal) is a more
      sensitive substrate for beta-gal activity than 5-bromo-4-chloro-3-indolyl-beta-D
      galactoside (X-gal). S-gal is advantageous where beta-gal activity is limited
      including early stage mouse embryos. As a result of the increased sensitivity as
      well as the color compatibility of S-gal, we successfully combined beta-gal
      staining using S-gal with in situ hybridization using DIG-labeled probes in both
      whole mounts and sections.

PMID- 24318811
TI  - Two-color in situ hybridization of whole-mount mouse embryos.
AB  - RNA in situ hybridization is a powerful technique used to identify the spatial
      localization of a specific RNA in a tissue section or whole tissue. In this
      protocol, we describe a reliable method for two-color in situ hybridization that
      can be used to accurately assess the expression of multiple genes with
      contrasting or overlapping expression patterns in whole mouse embryos. 

PMID- 24318812
TI  - Detection and monitoring of microRNA expression in developing mouse brain and
      fixed brain cryosections.
AB  - MicroRNAs (miRNAs) are 20-25 nucleotide long, noncoding, and single-strand RNAs
      that have been found in almost all organisms and shown to exert essential roles
      by regulating the stability and translation of target mRNAs. In mammals most
      miRNAs show tissue specific and developmentally regulated expression.
      Approximately 70 % of all miRNAs are expressed in the brain and a growing number
      of studies have shown that miRNAs can modulate both brain development function
      and dysfunction. Moreover, miRNAs have been involved in a variety of human
      pathologies, including cancer and diabetes and are rapidly emerging as new
      potential drug targets. In order to further characterize miRNA functions, it is
      therefore crucial to develop techniques enabling their detection in tissues (both
      fixed and in vivo) with single-cell resolution. Here, we describe methods for the
      detection/monitoring of miRNA expression, that can be applied in both developing
      embryos and fixed samples, which we and others have applied to the investigation
      of both embryonal and postnatal neurogenesis in mice, but also in zebrafish, and
      cell cultures. 

PMID- 24318813
TI  - Laser capture microdissection of embryonic cells and preparation of RNA for
      microarray assays.
AB  - In order to compare the global gene expression profiles of different embryonic
      cell types, it is first necessary to isolate the specific cells of interest. The
      purpose of this chapter is to provide a step-by-step protocol to perform laser
      capture microdissection (LCM) on embryo samples and obtain sufficient amounts of
      high-quality RNA for microarray hybridizations. Using the LCM/microarray strategy
      on mouse embryo samples has some challenges, because the cells of interest are
      available in limited quantities. The first step in the protocol is to obtain
      embryonic tissue, and immediately cryoprotect and freeze it in a cryomold
      containing Optimal Cutting Temperature freezing media (Sakura Finetek), using a
      dry ice-isopentane bath. The tissue is then cryosectioned, and the microscope
      slides are processed to fix, stain, and dehydrate the cells. LCM is employed to
      isolate specific cell types from the slides, identified under the microscope by
      virtue of their morphology. Detailed protocols are provided for using the
      currently available ArcturusXT LCM instrument and CapSure((r)) LCM Caps, to which
      the selected cells adhere upon laser capture. To maintain RNA integrity, upon
      removing a slide from the final processing step, or attaching the first cells on
      the LCM cap, LCM is completed within 20 min. The cells are then immediately
      recovered from the LCM cap using a denaturing solution that stabilizes RNA
      integrity. RNA is prepared using standard methods, modified for working with
      small samples. To ensure the validity of the microarray data, the quality of the
      RNA is assessed using the Agilent bioanalyzer. Only RNA that is of sufficient
      integrity and quantity is used to perform microarray assays. This chapter
      provides guidance regarding troubleshooting and optimization to obtain high
      quality RNA from cells of limited availability, obtained from embryo samples by
      LCM. 

PMID- 24318814
TI  - EMAGE: Electronic Mouse Atlas of Gene Expression.
AB  - The EMAGE (Electronic Mouse Atlas of Gene Expression) database
      (http://www.emouseatlas.org/emage) allows users to perform on-line queries of
      mouse developmental gene expression. EMAGE data are represented spatially using a
      framework of 3D mouse embryo models, thus allowing uniquely spatial queries to be
      carried out alongside more traditional text-based queries. This spatial
      representation of the data also allows a comparison of spatial similarity between
      the expression patterns. The data are mapped to the models by a team of curators
      using bespoke mapping software, and the associated meta-data are curated for
      accuracy and completeness. The data contained in EMAGE are gathered from three
      main sources: from the published literature, through large-scale screens and
      collaborations, and via direct submissions from researchers. There are a variety
      of ways to query the EMAGE database via the on-line search interfaces, as well as
      via direct computational script-based queries. EMAGE is a free, on-line,
      community resource funded by the Medical Research Council, UK.

PMID- 24318815
TI  - Real-time PCR quantification of gene expression in embryonic mouse tissue.
AB  - The Gbx family of transcription factors consists of two closely related proteins
      GBX1 and GBX2. A defining feature of the GBX family is a highly conserved 60
      amino acid DNA-binding domain, which differs by just two amino acids. Gbx1 and
      Gbx2 are co-expressed in several areas of the developing central nervous system
      including the forebrain, anterior hindbrain, and spinal cord, suggesting the
      potential for genetic redundancy. However, there is a spatiotemporal difference
      in expression of Gbx1 and Gbx2 in the forebrain and spinal cord. Gbx2 has been
      shown to play a critical role in positioning the midbrain/hindbrain boundary and
      developing anterior hindbrain, whereas gene-targeting experiments in mice have
      revealed an essential function for Gbx1 in the spinal cord for normal locomotion.
      To determine if Gbx2 could potentially compensate for a loss of Gbx1 in the
      developing spinal cord, we performed real-time PCR to examine levels of Gbx2
      expression in Gbx1(-/-) spinal cord at embryonic day (E) 13.5, a developmental
      stage when Gbx2 is rapidly downregulated. We demonstrate that Gbx2 expression is
      elevated in the spinal cord of Gbx1(-/-) embryos.

PMID- 24318816
TI  - Identifying essential genes in mouse development via an ENU-based forward genetic
      approach.
AB  - The completion of the human and mouse genome projects at the beginning of the
      past decade represented a very important step forward in our pursuit of a
      comprehensive understanding of the genetic control of mammalian development.
      Nevertheless, genetic analyses of mutant phenotypes are still needed to
      understand the function of individual genes. The genotype-based approaches,
      including gene-trapping and gene-targeting, promise a mutant embryonic stem (ES)
      cell resource for all the genes in mouse genome; however, the phenotypic
      consequences of these mutations will not be addressed until mutant mice are
      derived from these ES cells, which is not trivial. An efficient and non-biased, N
      ethyl-N-nitrosourea (ENU)-based forward genetic approach in mouse provides a
      unique tool for the identification of genes essential for development and adult
      physiology. We have had great success in identifying genes essential for
      morphogenesis and early patterning of mouse via this approach. Combined with
      complete genome information and numerous genetic resources available, ENU-based
      mutagenesis has become a powerful tool in deciphering gene functions. 

PMID- 24318817
TI  - Generation of mouse embryos with small hairpin RNA-mediated knockdown of gene
      expression.
AB  - We are using knockdown of gene expression in mouse embryos by constitutive
      expression of small hairpin (sh)RNAs as a means of observing loss-of-function
      phenotypes more rapidly than gene targeting. Plasmid constructs that direct shRNA
      expression via an RNA pol III promoter are introduced into embryonic stem (ES)
      cells by electroporation and drug selection. Clones are propagated and the degree
      of knockdown assessed by quantitative protein or RNA methods. Selected ES cell
      clones are used to generate embryos by tetraploid complementation. Blastomeres of
      two cell embryos are electrofused to generate tetraploid embryos. Chimeric
      embryos are produced by injection of ES cells into blastocysts or aggregation
      with morulae. In these embryos, the tetraploid cells become excluded from the
      fetal tissues, resulting in ES cell-derived embryos harboring the shRNA knockdown
      construct. Embryos can be collected and their phenotype assessed by appropriate
      means. 

PMID- 24318818
TI  - Generation of tissue organoids by compaction reaggregation.
AB  - Cellular reaggregation methods are commonly used to generate tissue organoids for
      use in biological studies. Using a modified method termed "compaction
      reaggregation," it is possible to establish reaggregates of reproducible size
      from defined input cell numbers with ease and without specialist equipment.
      Importantly, this method is suitable for the study of tissues that have proved
      refractory to reaggregation by other methods. With the option of juxtaposing cell
      populations, this method is useful for studies of tissue organization and
      structure. 

PMID- 24318819
TI  - Ultrarapid vitrification of mouse oocytes and embryos.
AB  - Cryopreservation facilitates long-term storage of gametes and embryos for
      numerous purposes. For example, cryobanking of unique mouse strains, particularly
      transgenic mice, offers important protection of valuable genetics. It also
      provides a practical solution for facilities trying to house large numbers of
      research animals or those looking to relocate without the risk of introducing an
      animal-derived pathogen. Furthermore, cryopreservation is currently being used
      for fertility preservation both in humans and as a safeguard for endangered
      animals. Ultrarapid vitrification offers an elegant, quick, and very reliable
      method for cryopreservation of mouse oocytes and embryos. Furthermore, research
      into the effects on mouse oocyte and embryo physiology has indicated that
      ultrarapid vitrification is superior to conventional slow freezing. High survival
      rates, embryo development, and viability are routinely achieved with the
      ultrarapid vitrification method described in this chapter. 

PMID- 24318820
TI  - Mammalian preimplantation embryo culture.
AB  - Since the inception of modern embryo culture media over 50 years ago there have
      been significant developments in culture systems for the mammalian
      preimplantation embryo. Carbohydrate gradients have been shown to impact embryo
      physiology and viability, while amino acids have been determined to have specific
      temporal effects during the preimplantation period. Furthermore, due to the
      lability of amino acids at 37  degrees C and the subsequent release of embryo
      toxic ammonium into the medium, the medium is renewed every 48 h not only to
      provide stage-specific nutrients but also to prevent toxicity. Subsequently stage
      specific media are commonly employed. To facilitate the preparation of small
      volumes of media, whose formulations can be readily altered according to
      experimental design, the use of stock solutions is described, together with
      systems to facilitate the development of viable embryos. 

PMID- 24318821
TI  - Serum-free culture of mid-gestation mouse embryos: a tool for the study of
      endoderm-derived organs.
AB  - The experimental manipulation of mid-gestation mouse embryos is an important tool
      for the study of developmental biology. However, such techniques can be
      challenging due to difficulties accessing the embryos in utero, and therefore the
      ability to maintain mid-gestation mouse embryos in vitro has proved invaluable.
      Described here is an example of a whole embryo culture system, where a serum-free
      medium is used to support the development of mouse embryos in vitro from
      embryonic day 10.5 (E10.5) to E11.5. During this time the embryos increase in
      size and undergo developmental progression, as determined by morphological and
      molecular criteria. This makes it an ideal environment in which to support and
      maintain mid-gestation mouse embryos following experimental manipulations. Two
      applications of this whole embryo culture system are described here. In the
      first, protein-soaked beads are carefully positioned in the pharyngeal region of
      an E10.5 embryo, allowing the concentration of specific proteins to be altered
      within the tissue. In the second technique, morpholino oligonucleotides are
      electroporated into the pharyngeal region of the embryo at E10.5, creating an
      efficient system for the knockdown of gene function in the target cells. These
      techniques demonstrate the use of in vitro techniques to study organogenesis
      within the pharyngeal region of the mouse embryo, but with some modification they
      could be adapted to target any region of the endodermal gut tube.

PMID- 24318822
TI  - Genetically encoded probes provide a window on embryonic arrhythmia.
AB  - Supraventricular tachycardias are the most prevalent group of arrhythmias
      observed in the fetus and infant and their incidence increases through early
      childhood. The molecular pathogenesis of embryonic cardiac dysfunction is poorly
      understood, due in part to the absence of imaging techniques that provide
      functional information at the cellular and molecular levels in the developing
      mammalian heart, particularly during early heart formation. The combination of
      protein engineering, genetic specification, and high-resolution optical imaging
      enables new insights into cardiac function and dysfunction during cardiac
      development. Here we describe the use of GCaMP2, a genetically encoded Ca(2+)
      indicator (GECI), to determine the processes of cardiac electrical activation
      during cardiac organogenesis. Transgenic specification of GCaMP2 in mice allows
      sufficient expression for Ca(2+) imaging as early as embryonic day (e.d.) 9.5,
      just after the heart begins to function at e.d. 8.5. Crosses with knockout lines
      in which lethality occurs due to cardiac dysfunction will enable precise
      determination of the conduction or excitation-contraction coupling phenotypes and
      thereby improve the understanding of the genetic basis of heart development and
      the consequence of gene mutations. Moreover, lineage-specific targeting of these
      sensors of cell signaling provides a new window on the molecular specification of
      the heart conduction system. We describe mouse lines and imaging methods used to
      examine conduction in the pre-septated heart (e.d. 10.5), which occurs through
      dramatically slowed atrioventricular (AV) canal conduction, producing a delay
      between atrial and ventricular activation prior to the development of the AV
      node. Genetic constructs including single and bi-allelic minimal promoter
      systems, and single allele BAC transgenes, enable general or lineage-specific
      targeting of GCaMP2. High-resolution imaging of embryonic heart conduction
      provides a new window on one of the most complex events in the mammalian body
      plan. 

PMID- 24318823
TI  - Microscopic computed tomography-based skeletal phenotyping for genetic model
      organisms.
AB  - Forward and reverse genetics now enable researchers to understand embryonic and
      postnatal gene functioning in a wide range of species. Some genetic mutations
      cause obvious morphological change, whereas other mutations can lead to more
      subtle phenotypes and might be overlooked without adequate observations and
      quantifications. Due to the increase in number of genetic model organisms
      examined by the growing field of phenomics, standardized but sensitive methods
      for quantitative analysis are increasingly necessary in the everyday practice of
      analyzing ever-increasing quantities of phenotypic data. In this chapter, we have
      presented platform-independent parameters for the use of microscopic X-ray
      computed tomography (microCT) for phenotyping species-specific skeletal
      morphology of a variety of different genetic model organisms. 

PMID- 24318824
TI  - Gene transfer techniques in whole embryo cultured post-implantation mouse
      embryos.
AB  - Gene transfer techniques such as electroporation and lipofection are powerful
      systems for investigating gene function. In this chapter we focus on the methods
      and applications of gene transfer into specific cells and tissues of post
      implantation mouse embryos. 

PMID- 24318825
TI  - Segmentation and quantitative analysis of individual cells in developmental
      tissues.
AB  - Image analysis is vital for extracting quantitative information from biological
      images and is used extensively, including investigations in developmental
      biology. The technique commences with the segmentation (delineation) of objects
      of interest from 2D images or 3D image stacks and is usually followed by the
      measurement and classification of the segmented objects. This chapter focuses on
      the segmentation task and here we explain the use of ImageJ, MIPAV (Medical Image
      Processing, Analysis, and Visualization), and VisSeg, three freely available
      software packages for this purpose. ImageJ and MIPAV are extremely versatile and
      can be used in diverse applications. VisSeg is a specialized tool for performing
      highly accurate and reliable 2D and 3D segmentation of objects such as cells and
      cell nuclei in images and stacks. 

PMID- 24318826
TI  - Protein/peptide transduction in metanephric explant culture.
AB  - While gene targeting methods have largely supplanted cell/explant culture models
      for studying developmental processes, they have not eliminated the need for or
      value of such approaches in the investigator's technical arsenal. Explant culture
      models, such as those devised for the metanephric kidney and its progenitors,
      remain invaluable as tools for screening regulatory factors involved in tissue
      induction or in the inhibition of progenitor specification. Thus, some factors
      capable of inducing tissue condensations or nephronic tubule formation in
      explants of metanephric mesenchyme have been identified through direct treatment
      of cultures rather than lengthy genetic engineering in animals. Unfortunately,
      renal progenitors are largely refractory to most contemporary methods for gene
      manipulation, including transfection and viral transduction, so the applications
      of explant culture have been rather limited. However, methods for protein or
      peptide transduction offer greatly improved efficiencies for uptake and
      expression/regulation of proteins within cells and tissues. Biologically active
      TAT- or penetratin-fusion proteins/peptides are readily taken up by most cells in
      metanephric explants or monolayer cultured cells (Plisov et al., J Am Soc Nephrol
      16:1632-1644, 2005; Osafune et al., Development 133:151-161, 2006; Wang et al.,
      Cell Signal 22:1717-1726, 2010; Tanigawa, Dev Biol 352:58-69, 2011), allowing a
      direct functional evaluation of theoretically any protein, including biologically
      active enzymes and transcription factors, or any targeted interactive domain
      within a protein. 

PMID- 24318827
TI  - Detection of cells programmed to die in mouse embryos.
AB  - Programmed Cell Death (PCD) is a broad term used to describe a series of events
      that culminate in the death of specific cells. In the embryo it occurs at
      predictable stages and tissues. During mouse development, PCD is a mechanism to
      preserve the homeostasis of the growing organism, and also is needed for the
      morphogenesis of a variety of structures. Apoptosis or PCD type I shows a
      sequence of morphological and biochemical changes such as plasma membrane
      blebbing, increase in mitochondrial membrane permeability, caspase activation,
      chromatin condensation, and phagocytosis. Many of these changes can be used to
      determine the occurrence of apoptosis in different type of samples. For example,
      apoptosis has been visualized in whole embryos and tissue sections using vital
      dyes, and by detection of degraded DNA or active caspases. In the present report,
      we compare these methods during the course of interdigital cell death in the
      mouse limbs. We discuss which method is the most suitable to detect a particular
      stage of apoptosis, which in some cases may be relevant for the interpretation of
      data. We detail combined protocols to observe mRNA expression or protein and cell
      death in the same tissue sample. Furthermore, we discuss some of the
      methodological problems to analyze autophagic cell death or PCD type II during
      embryo development. 

PMID- 24318828
TI  - Microscopic computed tomography-based virtual histology of embryos.
AB  - Advances in imaging technologies and computational capabilities have made
      possible novel methods for phenotypic assessments and visualization of detailed
      anatomical structures of whole embryos. We recently reported a rapid and
      inexpensive technique for achieving high-resolution virtual histology for
      phenotyping assessment of mouse embryos (Johnson et al., PLoS Genet 2:e61, 2006).
      By en bloc staining in a solution of electron-dense osmium tetroxide followed by
      volumetric X-ray computed tomography, whole embryos can be imaged at isometric
      resolutions as high as 2.5 MUm, depending on the size of the specimen. The
      datasets generated by these techniques are compatible with state-of-the-art
      computational methods of organ pattern analysis. This method of Microscopic
      Computed Tomography (microCT)-based Virtual Histology of embryos allows one to
      rapidly and accurately phenotype transgenic embryos or to engage in developmental
      and reproductive toxicology studies of investigational drugs at better
      resolution, less time, and less expense than traditional histology, magnetic
      resonance microscopy, or the classical Wilson and Staples procedures. 

PMID- 24318829
TI  - Collection and preparation of rodent embryonic samples for transcriptome study.
AB  - The need for large-scale collection of rodent embryos and individual embryonic
      tissues for genomic and proteomic studies requires modification of traditional
      practices of embryo necropsy. The sample intended for transcriptome study should
      be rapidly dissected and stabilized to preserve its molecular integrity. The
      retrieval of high-quality RNA, DNA, and proteins from the target tissue is
      crucial for informative molecular analysis (e.g., gene profiling on microarray
      platform). We present a reliable method of collection and preparation of rodent
      embryos for genomic studies supported by detailed protocols and RNA extraction
      results for different stages of mouse embryonic development. 

PMID- 24318830
TI  - The latest improvements in the mouse sperm preservation.
AB  - Sperm preservation is an important technique for maintaining valuable genetic
      resources in biomedical research and wildlife. In the mouse, the sperm
      cryopreservation method has been established and adopted by large-scale sperm
      preservation projects in cryobanks. Recently, a new sperm preservation method
      using freeze-drying has been studied in various mammals. Freeze-drying is the
      ultimate method by which sperm can be preserved long term in a refrigerator (4 
      degrees C). And it is possible to realize easy and safe transportation of sperm
      at an ambient temperature that requires neither liquid nitrogen nor dry ice.
      Furthermore, it has been demonstrated that the fertilizing ability of sperm
      cryopreserved or freeze-dried by the methods described in this chapter is well
      maintained during long-term preservation. This chapter introduces the latest
      protocols for cryopreservation and freeze-drying of mouse sperm, and the
      anticipated results of the fertilizing ability of these sperm preserved long
      term. 

PMID- 24318831
TI  - Analyzing gene function in whole mouse embryo and fetal organ in vitro.
AB  - A well-established experimental paradigm to analyze gene function in development
      is to elucidate the impact of gain and loss of gene activity on cell
      differentiation, tissue modelling, organogenesis, and morphogenesis. This chapter
      describes the experimental protocols to study gene function by means of
      electroporation and lipofection to manipulate genetic activity in whole embryos
      and fetal organs in vitro. These techniques allow for more precise control of the
      timing, with reference to developmental age or stage, and the cell/tissue
      specificity of the changes in gene activity. They provide an alternative strategy
      that can expedite the analysis of gene function before resorting to the
      conventional means of transgenesis and gene targeting in the whole organism. 

PMID- 24318832
TI  - Using the Textpresso Site-Specific Recombinases Web server to identify Cre
      expressing mouse strains and floxed alleles.
AB  - Effective tools for searching the biomedical literature are essential for
      identifying reagents or mouse strains as well as for effective experimental
      design and informed interpretation of experimental results. We have built the
      Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable
      researchers who use mice to perform in-depth searches of a rapidly growing and
      complex part of the mouse literature. Our Textpresso Web server provides an
      interface for searching the full text of most of the peer-reviewed publications
      that report the characterization or use of mouse strains that express Cre or Flp
      recombinase. The database also contains most of the publications that describe
      the characterization or analysis of strains carrying conditional alleles or
      transgenes that can be inactivated or activated by site-specific recombinases
      such as Cre or Flp. Textpresso SSR complements the existing online databases that
      catalog Cre and Flp expression patterns by providing a unique online interface
      for the in-depth text mining of the site specific recombinase literature. 

PMID- 24318834
TI  - Genetic cell ablation.
AB  - Targeted cell ablation has proven to be a valuable approach to study in vivo cell
      functions during organogenesis, tissue homeostasis, and regeneration. Over the
      last two decades, various approaches have been developed to refine the control of
      cell ablation. In this review, we give an overview of the distinct genetic tools
      available for targeted cell ablation, with a particular emphasis on their
      respective specificity. 

PMID- 24318833
TI  - Live imaging mouse embryonic development: seeing is believing and revealing.
AB  - The use of genetically encoded fluorescent proteins has revolutionized the fields
      of cell and developmental biology and redefined our understanding of the dynamic
      morphogenetic processes that work to shape the embryo. Fluorescent proteins are
      routinely used as vital reporters to label tissues, cells, cellular organelles,
      or proteins of interest and in doing so provide contrasting agents enabling the
      acquisition of high-resolution quantitative image data. With the advent of more
      accessible and sophisticated imaging technologies and abundance of fluorescent
      proteins with different spectral characteristics, the dynamic processes taking
      place in situ in living embryos can now be probed. Here, we provide an overview
      of some recent advances in this rapidly evolving field. 

PMID- 24318835
TI  - Essentials of recombinase-based genetic fate mapping in mice.
AB  - Fate maps, by defining the relationship between embryonic tissue organization and
      postnatal tissue structure, are one of the most important tools on hand to
      developmental biologists. In the past, generating such maps in mice was hindered
      by their in utero development limiting the physical access required for
      traditional methods involving tracer injection or cell transplantation. No longer
      is physical access a requirement. Innovations over the past decade have led to
      genetic techniques that offer means to "deliver" cell lineage tracers
      noninvasively. Such "genetic fate mapping" approaches employ transgenic
      strategies to express genetically encoded site-specific recombinases in a cell
      type-specific manner to switch on expression of a cell-heritable reporter
      transgene as lineage tracer. The behaviors and fate of marked cells and their
      progeny can then be explored and their contributions to different tissues
      examined. Here, we review the basic concepts of genetic fate mapping and consider
      the strengths and limitations for their application. We also explore two
      refinements of this approach that lend improved spatial and temporal resolution:
      (1) Intersectional and subtractive genetic fate mapping and (2) Genetic inducible
      fate mapping. 

PMID- 24318837
TI  - Emission of air pollutants from burning candles with different composition in
      indoor environments.
AB  - Candle composition is expected to influence the air pollutants emissions,
      possibly leading to important differences in the emissions of volatile organic
      compounds and polycyclic aromatic hydrocarbons. In this regard, the purity of the
      raw materials and additives used can play a key role. Consequently, in this work
      emission factors for some polycyclic aromatic hydrocarbons, aromatic species,
      short-chain aldehydes and particulate matter have been determined for container
      candles constituted by different paraffin waxes burning in a test chamber. It has
      been found that wax quality strongly influences the air pollutant emissions.
      These results could be used, at least at a first glance, to foresee the expected
      pollutant concentration in a given indoor environment with respect to health
      safety standards, while the test chamber used for performing the reported results
      could be useful to estimate the emission factors of any other candle in an easy
      to-build standardised environment. 

PMID- 24318836
TI  - Mass drug administration for malaria.
AB  - BACKGROUND: Mass drug administration (MDA), defined as the empiric administration
      of a therapeutic antimalarial regimen to an entire population at the same time,
      has been a historic component of many malaria control and elimination programmes,
      but is not currently recommended. With renewed interest in MDA and its role in
      malaria elimination, this review aims to summarize the findings from existing
      research studies and program experiences of MDA strategies for reducing malaria
      burden and transmission. OBJECTIVES: To assess the impact of antimalarial MDA on
      population asexual parasitaemia prevalence, parasitaemia incidence,
      gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated
      adverse events. SEARCH METHODS: We searched the Cochrane Infectious Disease Group
      Specialized Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts,
      LILACS, reference lists, and recent conference proceedings. SELECTION CRITERIA:
      Cluster-randomized trials and non-randomized controlled studies comparing
      therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after
      studies comparing post-MDA to baseline data were selected. Studies administering
      intermittent preventive treatment (IPT) to sub-populations (for example, pregnant
      women, children or infants) were excluded. DATA COLLECTION AND ANALYSIS: Two
      authors independently reviewed studies for inclusion, extracted data and assessed
      risk of bias. Studies were stratified by study design and then subgrouped by
      endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and
      by plasmodium species. The quality of evidence was assessed using the GRADE
      approach. MAIN RESULTS: Two cluster-randomized trials, eight non-randomized
      controlled studies and 22 uncontrolled before-and-after studies are included in
      this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no
      intervention of which two comparisons were conducted in areas of low endemicity
      (<=5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high
      endemicity (>= 40%). Ten studies evaluated MDA plus other vector control
      measures. The studies used a wide variety of MDA regimens incorporating different
      drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now
      more than 30 years old. Areas of low endemicity (<=5%)Within the first month post
      MDA, a single uncontrolled before-and-after study conducted in 1955 on a small
      Taiwanese island reported a much lower prevalence of parasitaemia following a
      single course of chloroquine compared to baseline (1 study, very low quality
      evidence). This lower parasite prevalence was still present after more than 12
      months (one study, very low quality evidence). In addition, one cluster
      randomized trial evaluating MDA in a low endemic setting reported zero episodes
      of parasitaemia at baseline, and throughout five months of follow-up in both the
      control and intervention arms (one study, very low quality evidence). Areas of
      moderate endemicity (6-39%)Within the first month post-MDA, the prevalence of
      parasitaemia was much lower in three non-randomized controlled studies from Kenya
      and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate
      quality evidence), and in three uncontrolled before-and-after studies conducted
      between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality
      evidence).The longest follow-up in these settings was four to six months. At this
      time point, the prevalence of parasitaemia remained substantially lower than
      controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to
      0.33, two studies, low quality evidence). In contrast, the two uncontrolled
      before-and-after studies found mixed results: one found no difference and one
      found a substantially higher prevalence compared to baseline (not pooled, two
      studies, very low quality evidence). Areas of high endemicity (>=40%)Within the
      first month post-MDA, the single cluster-randomized trial from the Gambia in 1999
      found no significant difference in parasite prevalence (one study, low quality
      evidence). However, prevalence was much lower during the MDA programmes in three
      non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95%
      CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month
      of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to
      0.49, four studies,low quality evidence).Four trials reported changes in
      prevalence beyond three months. In the Gambia, the single cluster-randomized
      trial found no difference at five months (one trial, moderate quality evidence).
      The three uncontrolled before-and-after studies had mixed findings with large
      studies from Palestine and Cambodia showing sustained reductions at four months
      and 12 months, respectively, and a small study from Malaysia showing no
      difference after four to six months of follow-up (three studies,low quality
      evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens
      that included 8-aminoquinolines with regimens that did not. In a crude subgroup
      analysis with a limited number of studies, we were unable to detect any evidence
      of additional benefit of primaquine in moderate- and high-transmission settings.
      Plasmodium species In studies that reported species-specific outcomes, the same
      interventions resulted in a larger impact on Plasmodium falciparum compared to P.
      vivax. AUTHORS' CONCLUSIONS: MDA appears to reduce substantially the initial risk
      of malaria parasitaemia. However, few studies showed sustained impact beyond six
      months post-MDA, and those that did were conducted on small islands or in
      highland settings.To assess whether there is an impact of MDA on malaria
      transmission in the longer term requires more quasi experimental studies with the
      intention of elimination, especially in low- and moderate-transmission settings.
      These studies need to address any long-term outcomes, any potential barriers for
      community uptake, and contribution to the development of drug resistance.

PMID- 24318838
TI  - Acetylcholinesterase protein level is preserved in the Alzheimer's brain.
AB  - Acetylcholinesterase (AChE) is a key enzyme in the cholinergic nervous system and
      is one of the most studied proteins in the field of Alzheimer's disease (AD).
      Moreover, alternative functions of AChE unrelated with the hydrolysis of
      acetylcholine are suspected. Until now, the majority of investigations on AChE in
      AD pathology have been focused on the determination of its enzymatic activity
      level, which is depleted in the AD brain. Despite this overall decrease, AChE
      activity increases at the vicinity of the two hallmarks of AD, the amyloid
      plaques and the neurofibrillary tangles (NFT). In fact, AChE may directly
      interact with Abeta in a manner that increases the deposition of Abeta to form
      plaques. In the context of protein-protein interactions, we have recently
      reported that AChE can interact with presenilin-1, the catalytic component of
      gamma-secretase, influencing its expression level and also its activity. However,
      the alteration of AChE protein in the AD brain has not been determined. Here, we
      demonstrated by Western blotting and immunohistochemistry that a prominent pool
      of enzymatically inactive AChE protein existed in the AD brain. The potential
      significance of these unexpected levels of inactive AChE protein in the AD brain
      was discussed, especially in the context of protein-protein interactions with
      beta-amyloid and presenilin-1. 

PMID- 24318840
TI  - Evolutionary analysis of voltage-gated potassium channels by Bayes method.
AB  - Voltage-gated potassium channels (VGPCs) are among the most complex families of
      ion channels. VGPCs are distributed widely among species but their biological
      roles remain unclear. In this study, the evolution of VGPCs and the functions of
      ancestral families are determined according to phylogenetic studies. We
      downloaded 127 genomic data of alpha subunits and 38 genomic data of beta
      subunits including those from human, rat, mice, Drosophila and Puccinellia
      tenuiflora. The genetic neighborhood of subfamily genes was determined by
      neighbor-joining, minimum evolution, maximum parsimony, and Bayes methods. Data
      was presented as phylogenetic trees. We also detected positive selection sites by
      site model. New insights into the evolutionary history of the VGPC family are
      provided. Our assumptions are as follows: (a) KCNH subfamily is likely the most
      original subfamily in alpha subunit; (b) VGPCs are related to neural and cardiac
      systems at the earliest time; (c) KCNA4 and KCNF1 may be as ancestors; (d)
      abnormality in one gene may cause both cardiac and neural diseases; and (e)
      abnormalities in KCNH6 and KCNQ7 are more likely to cause cardiac diseases. 

PMID- 24318839
TI  - Urokinase plasminogen activator system in synovial fibroblasts from
      osteoarthritis patients: modulation by inflammatory mediators and neuropeptides.
AB  - Plasminogen activators are specific proteolytic enzymes implicated in a variety
      of basic biological processes. The expression of the urokinase plasminogen
      activator system components is increased in some human diseases, including
      osteoarthritis. We sought to study the effect of two components of the inflamed
      synovial microenvironment on this system, IL-1beta and fibronectin fragments,
      elucidating whether corticotropin-releasing factor (CRF) and vasoactive
      intestinal peptide (VIP) neuropeptides modulate it, and analyzing the
      physiological consequences in joint destruction by measuring matrix
      metalloproteinases-9 and metalloproteinases-13 levels in osteoarthritis
      fibroblast-like synoviocytes. We showed that IL-1beta and fibronectin fragments
      stimulated urokinase system contributing to the perpetuation of the destructive
      cascade in joint. VIP modulated, even at constitutive level, this system, also
      counteracting the effect of both inflammatory stimuli. However, CRF seemed to be
      ineffective in controlling the production of these proteinases. Moreover, VIP was
      able to reduce the constitutive expression of matrix metalloproteinase-13 and the
      levels of both matrix metalloproteinases after stimulation with the pro
      inflammatory stimuli. Our results suggest that the presence of early and later
      inflammatory mediators, such as IL-1beta and fibronectin fragments, increases the
      urokinase system and the matrix metalloproteinases levels. Whereas CRF did not
      affect this system, VIP counteracts these actions supporting its therapeutic
      potential for the treatment of osteoarthritis. 

PMID- 24318841
TI  - Microfungal contaminants on mobile phones of health services vocational school
      students in Marmaris, Turkey.
AB  - In this study, it was aimed to determine microfungi on mobile phones. Totally, 50
      mobile phones were used belonging to Health Services Vocational School students.
      The samples were taken by swabbing the screen and keys of mobile phones using
      moistened sterile swab sticks. A total of 24 different microfungal species were
      obtained belonging to Alternaria, Aspergillus, Cladosporium, Geotrichum,
      Penicillium, Phoma, Rhinocladiella, Scopulariopsis, Trichoderma, and Trichophyton
      genera. The genera of microfungi most abundant in terms of the number of species
      on the mobile phones were Aspergillus, Cladosporium, and Penicillium.
      Numerically, Cladosporium was found as the most abundant on the mobile phones.
      Cladosporium herbarum colonies were highest in number, followed by Cladosporium
      sphaerospermum, and Penicillium verrucosum var. cyclopium. When percentages of
      each species present on the mobile phones were considered, C. herbarum and C.
      sphaerospermum were the most common. There was a great similarity between the
      dominant microfungi isolated from mobile phones and dominant microfungi obtained
      from studies of atmospheric microfungi in Turkey.

PMID- 24318842
TI  - Sex pheromone of the pea moth,Cydia nigricana (F.) (Lepidoptera: Olethreutidae).
AB  - The sex pheromone of the pea moth,Cydia nigricana (F.), was identified as (E,E)
      8,10-dodecadien-1-ylacetate (E,E8,10-12?Ac) (approximately 0.1 ng/abdominal tip),
      in vacuum distillates of virgin female abdominal tips and volatiles emitted by
      calling females, from its chemical properties and capillary gas chromatography
      and mass spectrometry data. SyntheticE,E8,10-12?Ac and the natural pheromone
      elicited similar quantitative electrophysiological and behavioral responses from
      male moths. Other related compounds which also attract male moths in the
      field,viz., (E)-10-dodecen-1-yl acetate, (E,E)-8,10-dodecadien-1-ol, and (E,E)
      8,10-dodecadienal, were not detected in the pheromone andE,E8,10-12?Ac was not
      found in male moths. 

PMID- 24318843
TI  - Field and electroantennogram responses to sex pheromone optical isomers by
      monophagous jack pine sawflies (Hymenoptera: Diprionidae).
AB  - Several species of monophagous jack pine sawflies (Hymenoptera: Diprionidae) were
      tested in the field and by electroantennograms (EAG) for activity toward the
      optical isomers of a pine sawfly sex pheromone, the acetate and propionate esters
      of 3,7-dimethylpentadecan-2-ol.Neodiprion rugifrons andNeodiprion dubiosus were
      attracted to a mixture of the propionate esters of the 2S,3R,7R and 2S,3R,7S
      isomers, whereasNeodiprion swainei was attracted to the 2S,3S,7S propionate
      isomer. Samples containing the 2S,3R,7S propionate isomer elicited the strongest
      EAG responses in these three species andNeodiprion nigroscutum. The 2S,3S,7S
      propionate isomer was equally active (EAG) in the case ofN. swainei. 

PMID- 24318844
TI  - The attractivity of the female sex pheromone ofPeriplaneta americana and its
      components for conspecific males and males ofPeriplaneta australasiae in the
      field.
AB  - The attractivity of virgin female odors of the American cockroach was examined in
      field experiments. Crude extracts of the female odor, the isolated sex pheromone
      fractions, periplanone-A and periplanone-B, and other compounds obtained during
      the isolation served as stimulants. An extract of male odors, obtained by
      identical collection methods, was used as a control. Males ofPeriplaneta
      americana were attracted by the crude extract and periplanone-B; males of the
      sympatric species,P. Australasiae, by periplanone-A. Experiments in which these
      components were presented subsequently and as mixtures indicate that, under
      certain conditions, periplanone-A may also function as an attracting substance
      forP. americana males and that periplanone-B and possibly some other components
      act as an inhibitor for males ofP. australasiae. 

PMID- 24318845
TI  - Structure-activity relationship of stress-inducing odorants in the rat.
AB  - The stress for 12 sulfur-containing synthetized volatiles was evaluated in male
      Wistar rats and compared to that for fox-dropping extract concentrate. Stress
      behavior was analyzed by quantifying various stress responses in a standard open
      field and measuring the increase in plasma corticosterone concentration. Nine
      compounds induced stress-a dihydrothiazole, two cyclic polysulfides, five
      mercaptoketones, and a mercaptan. For the mercaptoketones, the following
      structure-activity relationships were observed. Size can vary considerably; the
      mercapto group can be either alpha or beta and either secondary or tertiary. The
      keto group is not essential, since a structurally related mercaptan remains
      active. The mercapto group is essential for activity in mercaptoketones, since
      conversion to a methyl sulfide resulted in a neutral response. This type of
      odorant could function as an allomone and may have potential in rat control as an
      area repellent. 

PMID- 24318846
TI  - Sources of fall armyworm,Spodoptera frugiperda (Lepidoptera: Noctuidae),
      kairomones eliciting host-finding behavior inCotesia (=Apanteles) marginivenitris
      (Hymenoptera: Braconidae).
AB  - Bioassay responses inCotesia marginiventris (Cresson) females to materials
      derived from fall armyworm (FAW) larvae,Spodoptera frugiperda (J. E. Smith), were
      most intense for frass and somewhat less intense for larval and pupal cutical
      materials, scales, exuviae, silk, and oral secretion, with FAW larval hemolymph
      eliciting only a slight response. The highest percentage of ovipositor probing
      was caused by frass (100%) and moth scales (90%). Various types of corn-leaf
      damage when assayed alone did not produce responses as intense as when assayed in
      combination with frass, cuticle material, and oral secretion. Parasitoid response
      was somewhat better to frass derived from FAW larvae feeding on corn and peanut
      leaves than from larvae feeding on the foliage of soybeans, Bermuda grass,
      cowpeas, or laboratory diet. Hexane and chloroform were better than methanol and
      water for extracting active material from FAW frass, and chloroform was the best
      of these solvents for extracting corn leaves. Serial dilutions of frass extracts
      resulted in a reduction in parasitoid response. 

PMID- 24318847
TI  - Quantitative variation of pheromone components in the spruce bark beetleIps
      typographus from different attack phases.
AB  - Ips typographus beetles were collected in the field, separated into eight attack
      phases (from beetles walking on the trunk of a tree under attack to those
      excavating gallery systems with a mother gallery longer than 4 cm), and
      immediately frozen in liquid nitrogen. 2-Methyl-3-buten-2-ol,cis- andtrans
      verbenol, verbenone, myrtenol, trans-myrtanol, ipsenol, ipsdienol, and 2
      phenylethanol were quantified from excised hindguts against an internal standard,
      heptyl acetate, in the extraction solvent. Methylbutenol, the pinene alcohols,
      and 2-phenylethanol showed the same pattern of variation between attack phases in
      males, with the largest amounts present before accepting females and then a fast
      decline. Ipsenol and ipsdienol were not detected in males before the females were
      accepted, and the amounts increased when the females start their egg laying.
      Verbenone occurred only in trace amounts. The beetles were sampled from five
      Norway spruce trees (Picea abies) of differing resin flow. The correlations
      between the nine pheromone components and five major host monoterpenes in the gut
      showed that the variation in the amount of methyl-butenol, ipsenol, and ipsdienol
      could not be explained by the variation in the amounts of host monoterpenes. In
      contrast over 80% of the quantitative variation ofcis-verbenol,trans-verbenol,
      and myrtenol was explained by the amount of alpha-pinene. The nine pheromone
      components from 36 individual males were also quantified. Both methylbutenol
      andcis-verbenol showed a large variation in both amounts and proportions. Females
      containedtrans-verbenol and traces of most other components found in males. When
      accepted by the male, they also contained a female-specific compound, beta
      isophorone. Behavioral and biosynthetic implications of the results are
      discussed. 

PMID- 24318848
TI  - Pheromone biosynthetic pathways: Conversion of ipsdienone to (-)-ipsdienol, a
      mechanism for enantioselective reduction in the male bark beetle,Ips
      paraconfusus.
AB  - The enantiomeric composition of the pheromone components (+)-ipsdienoI, e.e.
      87.6%, and (-)-ipsenol, e.e. 93.8%, produced by the male bark beetleIps
      paraconfusus (Scolytidae) under natural conditions was determined by HPLC
      separation of their diastereomeric ester derivatives. Males confined in an
      atmosphere of ipsdienone produced (-)-ipsdienol, e.e. 28%, and (-)-ipsenol, e.e.
      86%, indicating an enantiomeric selectivity in the conversion of the ketone to
      the alcohols. These findings demonstrate an enantioselective conversion mechanism
      in the biosynthetic pathway to the pheromones from myrcene, a host-plant terpene.

PMID- 24318849
TI  - Association of particular systems with the release of neutral lipids
      inEchinostoma revolutum (Trematoda) adults.
AB  - Since free sterol excretory-secretory (E-S) products are involved in pheromonal
      communication in adultEchinostoma revolutum (Trematoda), attempts were made to
      associate specific systems with the release of lipids from this organism. A
      micropipet design was used to isolate neutral lipids from the excretory system
      versus those obtained from both the alimentary and the reproductive systems.
      Tegumentary lipids were obtained by rubbing the surface of worms with gauze. As
      determined by thin-layer chromatography, the major neutral lipid obtained from
      all systems was free sterol. Additional minor neutral lipid fractions were
      obtained from the excretory, alimentary, and reproductive systems. Histochemical
      oil red O studies showed neutral lipids only in the excretory system. Neutral
      lipids released from all of the above-mentioned systems may play a role in
      pheromonal communication in this species. 

PMID- 24318850
TI  - The chemical feeding ecology ofNeodiprion dubiosus schedl,N. rugifrons midd.,
      andN. lecontei (Fitch) on jack pine (Pinus banksiana lamb.).
AB  - Two monophagous sawflies,Neodiprion dubiosus andN. rugifrons, actively avoid
      feeding on the current season's needles of jack pine,Pinus banksiana, while the
      polyphagousN. lecontei feeds indiscriminately on foliage of all age classes.
      Bioassay studies with needle extracts indicate thatN. dubiosus andN. rugifrons
      larval feeding preference is governed by a group of tricyclic diterpene resin
      acids. Resin acids commonly occur in needles of all ages; however, levopimaric,
      palustric, dehydroabietic, and neoabietic acids were at higher concentrations in
      the new needles.N. dubiosus was significantly deterred from feeding on 1-year-old
      foliage when treated with the pure resin acids, palustric and levopimaric, at 0.5
      and 1.0 mg/ml MeOH.N. rugifrons larvae were deterred from feeding by pure
      dehydroabietic, neoabietic, and palustric acids at 1.0 mg/ml MeOH. 

PMID- 24318851
TI  - Evaluation of time-average dispersion models for estimating pheromone
      concentration in a deciduous forest.
AB  - The Sutton and more recent Gaussian plume models of atmospheric dispersion were
      used to estimate downwind concentrations of pheromone in a deciduous forest. Wind
      measurements from two bivane anemometers were recorded every 12 sec and the
      pheromone was emitted from a point source 1.6 m above ground level at known
      rates. The wingfanning response of individually caged male gypsy moths (Lymantria
      dispar) at 15 sites situated 20 to 80 m downwind was used to monitor when
      pheromone levels were above threshold over a 15-min interval. Predicted
      concentrations from these Gaussian-type models at locations where wing fanning
      occurred were often several orders of magnitude below the known behavioral
      thresholds determined from wind tunnel tests. Probit analyses of dose-response
      relationships with these models showed no relationship between predicted dose and
      actual response. The disparity between the predictions of concentration from
      these models and the actual response patterns of the male gypsy moth in the field
      was not unexpected. These time-average models predict concentrations for a fixed
      position over 3-min or longer intervals, based upon the dispersion coefficients.
      Thus the models estimate pheromone concentrations for time intervals appreciably
      longer than required for behavioral response. 

PMID- 24318852
TI  - A substance which acts as a pH indicator from the mothEuchloron megaera L.
AB  - Wing scales of the mothEuchloron megaera L. (Sphingidae) contain a water-soluble
      green pigment showing pH indicator properties. This pigment has been isolated.
      The UV-visible spectra, the color changes, the reduction by dithionite, the
      polarity on SiO2 TLC, and the high molecular weight relate this pigment to an
      anthocyanidin derivative derived from the plant food. This result is discussed in
      connection with the presence of similar substances in plants of the family
      Apocynacea and in other moth species of the Sphingidae group, in which they play
      aposematic roles. As a hypothesis, it is suggested that the green pigment results
      from a reaction betweenNerium sp. anthocyanidins (plant food) and NH2 groups of
      basic constituents present in the animal. 

PMID- 24318853
TI  - Light-dependent toxicity of alpha-terthienyl and anthracene toward late embryonic
      stages ofRana pipiens.
AB  - Alpha-terthienyl is toxic to late embryonic stages ofRana pipiens in the presence
      of sunlight. Neither alpha-terthienyl alone in the dark nor a previously
      photolyzed solution of alpha-terthienyl has comparable activity. The LC50 was
      0.11 ppm with 30 min of exposure and 0.018 ppm with 2 hr of exposure to sunlight.
      Anthracene, a representative example of polycyclic aromatic hydrocarbons widely
      distributed in the environment, also showed similar phototoxicity, with an LC50
      of 0.065 ppm after 30 min of exposure and 0.025 ppm after 5 hr. 

PMID- 24318854
TI  - Response ofDiabrotica virgifera virgifera, D. v. Zeae, andD. porracea to
      stereoisomers of 8-methyl-2-decyl propanoate.
AB  - The four stereoisomers of 8-methyl-2-decyl propanoate were tested in the United
      States and Mexico for attractiveness toDiabrotica virgifera virgifera LeConte,
      the western corn rootworm,D. v. zeae Krysan and Smith, the Mexican corn rootworm,
      andD. porracea Harold. Males ofD. v. virgifera andD. v. zeae responded strongly
      to the (2R,8R)-isomer and secondarily to (2S,8R), whileD. ponacea responded
      exclusively to the (2S,8R)-isomer. The (2S,8S)- and (2R,8S)-isomers were inactive
      in all tests. Synergism or inhibition was not detected when various mixtures of
      the isomers were tested withD. v. virgifera. These phenomena were not tested
      withD. v. zeae andD. ponacea. 

PMID- 24318855
TI  - Response of the european elm bark beetle,Scolytus multistriatus, to host
      bacterial isolates.
AB  - The response of the European elm bark beetle,Scolytus multistriatus, to host
      bacterial isolates was studied qualitatively under field conditions. Initial
      experiments indicated that such isolates were attractive to in-flight beetles.
      These isolates, identified asBacillus subtilis (five strains),B. pumilus,
      andEnterobacter cloacae, were grown on nutrient agar in glass vials and attached
      to sticky traps in elm woods. Although beetles were caught on the bacterial
      isolate-baited traps, the catches were variable, inconsistent, and often
      contradictory from one experiment to another. High numbers ofS. multistriatus
      were caught on traps baited with three strains ofB. subtilis, but in addition to
      thesubtilis strains, there were also aerial contaminants in the treatments,
      namelyE. aerogenes, Corynebacterium sp., andFlavobacterium sp. Also, relatively
      high catches were recorded on nutrient agar controls. When elm wood-bark plugs,
      sterilized (by gamma irradiation) and unsterilized, were placed in vials with the
      host bacterial isolates, the presence or absence of fresh elm, gamma irradiated
      or not, had no noticeable effect on beetle attractancy. 

PMID- 24318856
TI  - Redefining "pharmacophagy".

PMID- 24318857
TI  - National critical incident reporting systems relevant to anaesthesia: a European
      survey.
AB  - BACKGROUND: Critical incident reporting is a key tool in the promotion of patient
      safety in anaesthesia. METHODS: We surveyed representatives of national incident
      reporting systems in six European countries, inviting information on scope and
      organization, and intelligence on factors determining success and failure.
      RESULTS: Some systems are government-run and nationally conceived; others started
      out as small, specialty-focused initiatives, which have since acquired a national
      reach. However, both national co-ordination and specialty enthusiasts seem to be
      necessary for an optimally functioning system. The role of reporting culture,
      definitional issues, and dissemination is discussed. CONCLUSIONS: We make
      recommendations for others intending to start new systems and speculate on the
      prospects for sharing patient safety lessons relevant to anaesthesia at European
      level.

PMID- 24318858
TI  - Bone cement embolism attached to central venous catheter.
AB  - We report on a rare complication of poly(methyl methacrylate) (PMMA), injected
      into the spine, which then inadvertently leaked into the venous system. This
      resulted in an embolism of PMMA and produced a mass surrounding a triple lumen
      central venous catheter located in the superior vena cava. The catheter as well
      as the attached mass of PMMA was retrieved safely by cardiothoracic surgery. This
      case emphasizes the importance of prompt diagnosis and treatment and illustrates
      the need for close monitoring of patients undergoing any spinal surgery that
      includes vertebroplasty. 

PMID- 24318859
TI  - Response to: 'Detection of antinuclear antibodies: added-value of solid phase
      assay?' by Bossuyt and Fieuws.

PMID- 24318860
TI  - The concept of axial spondyloarthritis. Lessons from the INFAST study.

PMID- 24318861
TI  - The role of weight, race, and health care experiences in care use among young men
      and women.
AB  - OBJECTIVE: Increases in overweight and obesity (O/O)-related morbidities and
      health care costs raise questions about how weight influences patients' health
      care use and care experiences. Past research has been inconsistent; however,
      prior study designs and samples have limited exploration of how this association
      might be influenced by gender, race, and the joint impact of these factors.
      METHODS: This analysis of 1,036 young, relatively healthy, ethnically diverse,
      insured adults assessed the influence of O/O, gender, and race on, and the role
      of health care experiences in primary and preventive care use over a 12-month
      period. RESULTS: The association of weight status with care use differed by
      gender. O/O men used more primary care visits; O/O women used fewer preventive
      care visits than their healthy weight counterparts. O/O men had poorer health
      care experiences than healthy weight men. African-American women reported poorer
      experiences, but those who were O/O reported greater trust in their provider.
      Care experience ratings did not explain the associations between BMI and care
      use. CONCLUSIONS: Gender, race, and visit type together provide a context for O/O
      patient's care that may not be explained by care experiences. This context must
      be considered in efforts to encourage appropriate use of services.

PMID- 24318862
TI  - The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East
      respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists.
AB  - The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is a
      highly pathogenic respiratory virus with pathogenic mechanisms that may be driven
      by innate immune pathways. The goal of this study is to characterize the
      expression of the structural (S, E, M, N) and accessory (ORF 3, ORF 4a, ORF 4b,
      ORF 5) proteins of MERS-CoV and to determine whether any of these proteins acts
      as an interferon antagonist. Individual structural and accessory protein-coding
      plasmids with an N-terminal HA tag were constructed and transiently transfected
      into cells, and their native expression and subcellular localization were
      assessed using Wes tern blotting and indirect immunofluorescence. While ORF 4b
      demonstrated majorly nuclear localization, all of the other proteins demonstrated
      cytoplasmic localization. In addition, for the first time, our experiments
      revealed that the M, ORF 4a, ORF 4b, and ORF 5 proteins are potent interferon
      antagonists. Further examination revealed that the ORF 4a protein of MERS-CoV has
      the most potential to counteract the antiviral effects of IFN via the inhibition
      of both the interferon production (IFN-beta promoter activity, IRF-3/7 and NF
      kappaB activation) and ISRE promoter element signaling pathways. Together, our
      results provide new insights into the function and pathogenic role of the
      structural and accessory proteins of MERS-CoV. 

PMID- 24318863
TI  - Pretreatment selection of regimen according to genetic analysis improves the
      efficacy of chemotherapy in the first line treatment of metastatic colorectal
      cancer.
AB  - BACKGROUND AND OBJECTIVES: Metastatic colon cancer patients are treated with the
      chemotherapy regimens, FOLFOX and FOLFIRI, in either order. So far, we cannot
      predict the response of chemotherapeutic agent, so it is necessary to find which
      regimen is adequate before starting chemotherapy. METHODS: Enrolled patients are
      randomized into either conventional treatment or planned treatment preceded by
      pretreatment genetic analysis. Blood samples of patients in planned treatment
      group (N = 53) were analyzed for the genetic polymorphism before selection of
      chemotherapeutic agents. Target genes were XPD-751, GSTP-1-105, XRCC1-399 for
      oxaliplatin, UGT1A1 for irinotecan. The response was measured by computed
      tomographic scan after completion of three cycles of chemotherapy. RESULTS:
      Overall response rate was significantly higher in planned group (67.9% vs. 46.3%,
      P = 0.020). In FOLFOX group, response rate was significantly improved in the
      planned patients(77.1% vs. 50%, P = 0.018). In FOLFIRI group, the difference
      didn't reach statistical significance (50% vs. 42.5%, P = 0.776). CONCLUSIONS: We
      found significantly improved response rates in the chemotherapy of metastatic
      colon cancer by pretreatment genetic analysis, especially in FOLFOX group.

PMID- 24318864
TI  - A brief anti-stigma intervention for Chinese immigrant caregivers of individuals
      with psychosis: adaptation and initial findings.
AB  - Mental illness stigma has adverse effects on both the caregivers' psychological
      well-being and the effectiveness of care that consumers receive. While anti
      stigma interventions for family caregivers from Western settings have recently
      shown efficacy, these interventions may not be equally applicable across
      culturally diverse groups. Specifically, Chinese immigrant caregivers experience
      heightened internalized stigma, which predisposes the adoption of harmful coping
      strategies and reduced quality of social networks. We present an anti-stigma
      intervention based on a peer-family group format, co-led by a clinician and a
      trained family caregiver, to counter stigma among Chinese immigrants. Data are
      presented from a brief intervention administered to a pilot sample of 11 Chinese
      immigrant caregivers that provides: psychoeducation, strategies to counter
      experienced discrimination, and techniques to resist internalized stigma. Case
      vignettes illustrate implementation of this intervention, and how the peer-family
      format via interactive contact counteracts internalized stereotypes, encourages
      adaptive coping strategies, and reinvigorates social networks. Quantitative
      results further suggest preliminary efficacy in reducing internalized stigma for
      caregivers who evidenced at least some prior internalized stigma. This study
      constitutes an initial but important step towards reducing mental illness stigma
      among Asian Americans, for whom stigma has played a powerful role in the delay
      and underuse of treatment. 

PMID- 24318865
TI  - Evaluation of cytogenetic and DNA damage caused by thallium(I) acetate in human
      blood cells.
AB  - Although thallium is detrimental to all living organisms, information regarding
      the mutagenic and genotoxic effects of this element and its compounds remains
      scarce. Therefore, we tested the genotoxic and cytotoxic effects of thallium(I)
      acetate on human peripheral blood cells in vitro using structural chromosomal
      aberrations (SCAs), sister chromatid exchanges (SCEs), and single-cell gel
      electrophoresis (at pH >13 or 12.1) analysis. Whole blood samples were incubated
      with 0.5, 1, 5, 10, 50, or 100 ug/mL thallium salt. Exposure to this metal
      compound resulted in a clear dose-dependent reduction in the mitotic and
      replicative indices. An increase in SCAs was evident in the treated group
      compared with the control group, and significant differences were observed in the
      percentage of cells with SCAs when metaphase cells were treated with 0.5-10 ug/mL
      of thallium(I). The SCE test did not reveal any significant differences. We
      observed that a 1-h treatment with thallium(I) at pH > 13 significantly increased
      the comet length for all the concentrations tested; however, at pH 12.1, only the
      two highest concentrations affected the comet length. These results suggested
      that thallium(I) acetate induces cytotoxic, cytostatic, and clastogenic effects,
      as well as DNA damage.

PMID- 24318866
TI  - Free tissue transfers in head and neck reconstruction: complications, outcomes
      and strategies for management of flap failure: analysis of 2019 flaps in single
      institute.
AB  - BACKGROUND: Free tissue transfer has become the preferred option for complex
      reconstructions in head and neck cancer ablation. This study reviewed the
      surgical outcome and analyzed the evolution of microsurgical head and neck
      reconstruction over 20 years in single institute. PATIENTS AND METHODS: A total
      of 1,918 patients underwent microsurgical head and neck reconstructions in 20
      year period. The surgical outcome and complications among these 2,019 flaps
      (1,223 anterolateral thigh flaps, 372 fibula flaps, 353 radial forearm flaps, 12
      jejunal flaps, and 59 others) were retrospectively reviewed and analyzed.
      RESULTS: A total of 201 cases required emergent surgical re-exploration and the
      overall flap success rate was 96.2%. Venous insufficiency was the most common
      cause for re-exploration. Other major complications included fistula formation
      (5.4%), partial flap necrosis (7.5%), and infection (17.8%). The fibula flap had
      frequent complications compared with soft tissue flaps. The familiarity to the
      ALT flap had minimized complications and allowed for widely versatile uses.
      CONCLUSION: Free tissue transfer is shown to be highly reliable option for head
      and neck reconstruction. For soft tissue defect, ALT flap is the first choice.
      Fibula flap is ideal for bone defect reconstruction. In case of complex composite
      defects, double flaps, which include ALT and fibula flaps could reconstruct bone
      and soft tissue defects simultaneously with high success rate.

PMID- 24318867
TI  - Influence of cadmium and nickel on growth, net photosynthesis and carbohydrate
      distribution in rice plants.
AB  - Six day old rice seedlings (Oryza sativa L. cv. Bahia) were grown for 5 or 10
      days in a nutrient solution with either Cd (0.01, 0.1 mmol/l) or Ni (0.1, 0.5
      mmol/l). Both Cd and Ni reduced the length of shoots and roots depending on the
      concentration and type of ion tested. On the other hand, the dry weight to fresh
      weight ratio was increased by heavy metal treatments, especially in the aerial
      part of 0.5 mmol/l Ni treated plants. The application of 0.1 mmol/l Cd and 0.5
      mmol/l Ni to the seedlings produced an inhibition of the transport of
      carbohydrate reserves from the seeds from which plants were developing, to the
      rest of the plant. Net photosynthesis was also inhibited in treated plants.
      However, the total carbohydrate content in the shoots of these plants was higher
      than in controls. Thus, the starch, soluble sugars and sucrose content in the
      shoots of 0.5 mmol/l Ni treated plants was respectively up to 2.6, 2.8 and 4
      times greater compared to controls. The distribution of assimilates between
      organs was also affected by the treatment: the carbohydrate content increased in
      the stem and second leaf but it was not affected or decreased in the root and
      third leaf. Although less evident, the effect of Cd on carbohydrate distribution
      and content was similar to that of Ni. The possible mechanisms involved in the
      abnormal carbohydrate accumulation and distribution are discussed. 

PMID- 24318868
TI  - Evidence for the contribution of the S-state transitions of oxygen evolution to
      the initial phase of fluorescence induction.
AB  - Fluorescence induction of isolated spinach chloroplasts was measured by using
      weak continuous light. It is found that the kinetics of the initial phase of
      fluorescence induction as well as the initial fluorescence level Fj are
      influenced by the number of preilluminating flashes, and shows damped period 4
      oscillation. Evidence is given to show that it is correlated with the S-state
      transitions of oxygen evolution. Based on the previous observations that the S
      states can modulate the fluorescence yield of Photosystem II, a simulating
      calculation suggests that, in addition to the Photosystem II centers inactive in
      the plastoquinone reduction, the S-state transitions can also make a contribution
      to the intial phase of fluorescence induction. 

PMID- 24318869
TI  - The degree of functional separation between the two photosystems in isolated
      thylakoid membranes deduced from inhibition studies of the imbalance in
      photoactivities.
AB  - In order to examine whether the two photosystems, PS I and PS II, are organized
      in specific electron transporting pairs, or randomly transport electrons from PS
      II to PS I, the photosystems imbalance of photoactivities (Emerson enhancement)
      was measured by modulated fluorimetry under different degrees of PS II inhibition
      in broken chloroplasts, where the granal structures were preserved by the
      presence of 5 mM MgCl. The results indicate a lack of any measurable specific
      functional pairing between individual PS I and PS II, in contrast to a previous
      research work in leaves (Malkin et al. 1986, Photosynth. Res. 10: 291-296). These
      results and this discrepancy are further discussed. 

PMID- 24318870
TI  - Redox control of gene expression and the function of chloroplast genomes - an
      hypothesis.
AB  - Two-component regulatory systems that respond to changes in redox potential have
      recently been discovered in bacteria. 'Redox sensors' are defined as electron
      carriers which initiate control of gene expression upon oxidation or reduction.
      'Redox response regulators' are defined as DNA-binding proteins which modify gene
      expression as a result of the action of redox sensors. Redox sensors and redox
      response regulators may comprise a mechanism for feedback control of redox
      potential in photosynthetic electron transport chains, thereby protecting plants,
      algae and photosynthetic bacteria from damage caused by electrochemistry
      operating on inappropriate electron donors and acceptors. Chloroplast redox
      sensors and redox response regulators, themselves encoded in the nucleus, may
      place chloroplast gene expression under redox regulatory control. This may
      account for the persistence, in evolution, of chloroplast genomes, and for the
      constancy of the sub-set of chloroplast proteins encoded and synthesised in situ.
      These and other predictions are discussed. 

PMID- 24318871
TI  - Effect of growth irradiance on plastocyanin levels in barley.
AB  - Plastocyanin levels in barley (Hordeum vulgare cv Boone) were found to be
      dependent on growth irradiance. An immunochemical assay was developed and used to
      measure the plastocyanin content of isolated thylakoid membranes. Barley grown
      under 600 MUmole photons m(-2)s(-1) contained two- to four-fold greater
      quantities of plastocyanin per unit chlorophyll compared with plants grown under
      60 MUmole photons m(-2)s(-1). The plastocyanin/Photosystem I ratio was found to
      be 2 to 3 under high irradiance compared with 0.5 to 1.5 under low irradiance.
      The reduced plastocyanin pool size in low light plants contributed to a two-fold
      reduction in photosynthetic electron transport activity. Plastocyanin levels
      increased upon transfer of low light plants to high irradiance conditions. In
      contrast, plastocyanin levels were not affected in plants transferred from high
      to low irradiance, suggesting that plastocyanin is not involved in the
      acclimation of photosynthesis to shade. 

PMID- 24318872
TI  - Oxygen evolution by Photosystem II: The contribution of backward transitions to
      the anomalous behaviour of double-hits revealed by a new analysis method.
AB  - Backward transitions in the analysis of oxygen production under flashing light
      were introduced by Packham et al., 1988, Photosynth. Res. 15: 221-232. In order
      to take backward transitions into account, a new method of analysis is presented:
      the 'eigenvalue method'. This method is based on the recurrence relation of
      oxygen production with four coefficients (also known as the four 'sigma'
      coefficients). It shows less susceptibility to round-off errors than other
      methods and permits the computation of double-hits directly from the
      coefficients, which was not possible before. With it we discovered that the
      inconsistent behaviour of double-hits observed previously under low flash
      intensities or low flash frequencies was mainly due to the inclusion of the
      backward transitions into the double-hit probability. In these conditions
      backward transitions seemed to be due either to the combination of an S-state
      deactivation and a miss, or to two S-state deactivations and a single-hit.In the
      presence of 3-(3, 4-Dichlorophenyl)-1, 1-dimethylurea (DCMU), the previous
      methods of 'sigma' analysis failed. In contrast, the new method resolved all four
      S-state probabilities; thus it has the further advantage of being more 'robust'
      (robustness being defined as the ability to yield a meaningful answer under
      difficult conditions). 

PMID- 24318873
TI  - Theoretical assessment of alternative mechanisms for non-photochemical quenching
      of PS II fluorescence in barley leaves.
AB  - The components of non-photochemical chlorophyll fluorescence quenching (qN) in
      barley leaves have been quantified by a combination of relaxation kinetics
      analysis and 77 K fluorescence measurements (Walters RG and Horton P 1991).
      Analysis of the behaviour of chlorophyll fluorescence parameters and oxygen
      evolution at low light (when only state transitions - measured as qNt - are
      present) and at high light (when only photoinhibition - measured as qNi - is
      increasing) showed that the parameter qNt represents quenching processes located
      in the antenna and that qNi measures quenching processes located in the reaction
      centre but which operate significantly only when those centres are closed. The
      theoretical predictions of a variety of models describing possible mechanisms for
      high-energy-state quenching, measured as the residual quenching, qNe, were then
      tested against the experimental data for both fluorescence quenching and quantum
      yield of oxygen evolution. Only one model was found to agree with these data, one
      in which antennae exist in two states, efficient in either energy transfer or
      energy dissipation, and in which those photosynthetic units in a dissipative
      state are unable to exchange energy with non-dissipative units. 

PMID- 24318874
TI  - On the question of the identity of cytochrome b-560 in thylakoid stromal
      membranes.
AB  - Stromal membranes enriched in PS I contain a low potential cytochrome with a
      reduced alpha-band peak close to 560 nm. The identity of this cytochrome
      component has been ascribed either to a low potential form of the Photosystem II
      cytochrome b-559 or to a different cytochrome with a reduced alpha-band of 560
      nm. The half-bandwidth of the 560 nm component in stromal membranes is identical
      to that of purified cytochrome b-559. Western blots show that the stromal
      membranes contain an amount of PS II cytochrome b-559 alpha-subunit that is more
      than sufficient to account for the cytochrome b-560 detected
      spectrophotometrically in these membranes. These immunochemical data and the
      similarity of (i) the spectral peaks, and (ii) the redox properties of low
      potential PS II cytochrome b-559 and the b-560 component, suggest that the
      simplest inference is that the cytochrome b-560 protein in stromal membranes is
      identical to the PS II cytochrome b-559. 

PMID- 24318875
TI  - Epigenetic regulation of miR-302 by JMJD1C inhibits neural differentiation of
      human embryonic stem cells.
AB  - It has been recently reported that the regulatory circuitry formed by OCT4, miR
      302, and NR2F2 controls both pluripotency and neural differentiation of human
      embryonic stem cells (hESCs). We show here that JMJD1C, a histone 3 lysine 9
      (H3K9) demethylase expressed in hESCs, directly interacts with this circuitry.
      hESCs with stable knockdown of JMJD1C remain pluripotent while having reduced miR
      302 expression, decreased BMP signaling, and enhanced TGFbeta signaling. JMJD1C
      binds to the miR-302 promoter and reduces H3K9 methylation. Withdrawal of basic
      fibroblast growth factor (bFGF) from the culture induces neural differentiation
      of the knockdown, but not the control, cells within 3 days, accompanied by
      elevated NR2F2 expression. This can be attenuated with miR-302 mimics or an H3K9
      methytransferase inhibitor. Together, our findings suggest that JMJD1C represses
      neural differentiation of hESCs at least partially by epigenetically sustaining
      miR-302 expression and that JMJD1C knockdown is sufficient to trigger neural
      differentiation upon withdrawal of exogenous bFGF. 

PMID- 24318876
TI  - Altered expression of small heterodimer partner governs cytochrome P450 (CYP) 2D6
      induction during pregnancy in CYP2D6-humanized mice.
AB  - Substrates of a major drug-metabolizing enzyme CYP2D6 display increased
      elimination during pregnancy, but the underlying mechanisms are unknown in part
      due to a lack of experimental models. Here, we introduce CYP2D6-humanized (Tg
      CYP2D6) mice as an animal model where hepatic CYP2D6 expression is increased
      during pregnancy. In the mouse livers, expression of a known positive regulator
      of CYP2D6, hepatocyte nuclear factor 4alpha (HNF4alpha), did not change during
      pregnancy. However, HNF4alpha recruitment to CYP2D6 promoter increased at term
      pregnancy, accompanied by repressed expression of small heterodimer partner
      (SHP). In HepG2 cells, SHP repressed HNF4alpha transactivation of CYP2D6
      promoter. In transgenic (Tg)-CYP2D6 mice, SHP knockdown led to a significant
      increase in CYP2D6 expression. Retinoic acid, an endogenous compound that induces
      SHP, exhibited decreased hepatic levels during pregnancy in Tg-CYP2D6 mice.
      Administration of all-trans-retinoic acid led to a significant decrease in the
      expression and activity of hepatic CYP2D6 in Tg-CYP2D6 mice. This study provides
      key insights into mechanisms underlying altered CYP2D6-mediated drug metabolism
      during pregnancy, laying a foundation for improved drug therapy in pregnant
      women.

PMID- 24318877
TI  - Binding of human nucleotide exchange factors to heat shock protein 70 (Hsp70)
      generates functionally distinct complexes in vitro.
AB  - Proteins with Bcl2-associated anthanogene (BAG) domains act as nucleotide
      exchange factors (NEFs) for the molecular chaperone heat shock protein 70
      (Hsp70). There are six BAG family NEFs in humans, and each is thought to link
      Hsp70 to a distinct cellular pathway. However, little is known about how the NEFs
      compete for binding to Hsp70 or how they might differentially shape its
      biochemical activities. Toward these questions, we measured the binding of human
      Hsp72 (HSPA1A) to BAG1, BAG2, BAG3, and the unrelated NEF Hsp105. These studies
      revealed a clear hierarchy of affinities: BAG3 > BAG1 > Hsp105 ? BAG2. All of the
      NEFs competed for binding to Hsp70, and their relative affinity values predicted
      their potency in nucleotide and peptide release assays. Finally, we combined the
      Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2,
      DnaJB1, and DnaJB4) to generate 16 permutations. The activity of the combinations
      in ATPase and luciferase refolding assays were dependent on the identity and
      stoichiometry of both the J protein and NEF so that some combinations were potent
      chaperones, whereas others were inactive. Given the number and diversity of
      cochaperones in mammals, it is likely that combinatorial assembly could generate
      a large number of distinct permutations. 

PMID- 24318878
TI  - Electric stimulus opens intercellular spaces in skin.
AB  - Iontophoresis is a technology for transdermal delivery of ionic small medicines
      by faint electricity. Since iontophoresis can noninvasively deliver charged
      molecules into the skin, this technology could be a useful administration method
      that may enhance patient comfort. Previously, we succeeded in the transdermal
      penetration of positively charged liposomes (diameters: 200-400 nm) encapsulating
      insulin by iontophoresis (Kajimoto, K., Yamamoto, M., Watanabe, M., Kigasawa, K.,
      Kanamura, K., Harashima, H., and Kogure, K. (2011) Int. J. Pharm. 403, 57-65).
      However, the mechanism by which these liposomes penetrated the skin was difficult
      to define based on general knowledge of principles such as electro-repulsion and
      electro-osmosis. In the present study, we confirmed that rigid nanoparticles
      could penetrate into the epidermis by iontophoresis. We further found that levels
      of the gap junction protein connexin 43 protein significantly decreased after
      faint electric stimulus (ES) treatment, although occludin, CLD-4, and ZO-1 levels
      were unchanged. Moreover, connexin 43 phosphorylation and filamentous actin
      depolymerization in vivo and in vitro were observed when permeation of charged
      liposomes through intercellular spaces was induced by ES. Ca(2+) inflow into
      cells was promoted by ES with charged liposomes, while a protein kinase C
      inhibitor prevented ES-induced permeation of macromolecules. Consequently, we
      demonstrate that ES treatment with charged liposomes induced dissociation of
      intercellular junctions via cell signaling pathways. These findings suggest that
      ES could be used to regulate skin physiology. 

PMID- 24318879
TI  - Role of annexin A5 in cisplatin-induced toxicity in renal cells: molecular
      mechanism of apoptosis.
AB  - Annexin A5 belongs to a large family of calcium-binding and phospholipid-binding
      proteins and may act as an endogenous regulator of various pathophysiological
      processes. There is increasing evidence that annexin A5 is related to
      cytotoxicity, but the precise function of this protein has yet to be elucidated.
      In this study, we aimed to verify the function of annexin A5 in the apoptosis of
      renal epithelial cells. Real-time PCR and Western blot analysis, together with
      immunofluorescence analysis, showed that the expression of annexin A5
      significantly increased in the presence of cisplatin in both human and rat renal
      epithelial cells. With regard to the mechanism of cisplatin-induced apoptosis,
      apoptosis-inducing factor (AIF) release into the cytosol was observed, and the
      underlying mechanism was identified as voltage-dependent anion channel (VDAC)
      oligomerization. Mitochondrial membrane potential (Deltapsim) was found to be
      greatly disrupted in cisplatin-treated cells. Moreover, cisplatin strongly
      induced translocation of annexin A5 into mitochondria. To understand the
      functional significance of annexin A5 in renal cell death, we used a siRNA
      mediated approach to knock down annexin A5. Annexin A5 depletion by siRNA led to
      decreased annexin A5 translocation into mitochondria and significantly reduced
      VDAC oligomerization and AIF release. Annexin A5 siRNA also increased cell
      viability compared with the control. Moreover, expression of annexin A5 was
      induced by other nephrotoxicants such as CdCl2 and bacitracin. Taken together,
      our data suggest that annexin A5 may play a crucial role in cisplatin-induced
      toxicity by mediating the mitochondrial apoptotic pathway via the induction and
      oligomerization of VDAC. 

PMID- 24318880
TI  - RGS6, but not RGS4, is the dominant regulator of G protein signaling (RGS)
      modulator of the parasympathetic regulation of mouse heart rate.
AB  - Parasympathetic activity decreases heart rate (HR) by inhibiting pacemaker cells
      in the sinoatrial node (SAN). Dysregulation of parasympathetic influence has been
      linked to sinus node dysfunction and arrhythmia. RGS (regulator of G protein
      signaling) proteins are negative modulators of the parasympathetic regulation of
      HR and the prototypical M2 muscarinic receptor (M2R)-dependent signaling pathway
      in the SAN that involves the muscarinic-gated atrial K(+) channel IKACh. Both
      RGS4 and RGS6-Gbeta5 have been implicated in these processes. Here, we used Rgs4(
      /-), Rgs6(-/-), and Rgs4(-/-):Rgs6(-/-) mice to compare the relative influence of
      RGS4 and RGS6 on parasympathetic regulation of HR and M2R-IKACh-dependent
      signaling in the SAN. In retrogradely perfused hearts, ablation of RGS6, but not
      RGS4, correlated with decreased resting HR, increased heart rate variability, and
      enhanced sensitivity to the negative chronotropic effects of the muscarinic
      agonist carbachol. Similarly, loss of RGS6, but not RGS4, correlated with
      enhanced sensitivity of the M2R-IKACh signaling pathway in SAN cells to carbachol
      and a significant slowing of M2R-IKACh deactivation rate. Surprisingly,
      concurrent genetic ablation of RGS4 partially rescued some deficits observed in
      Rgs6(-/-) mice. These findings, together with those from an acute pharmacologic
      approach in SAN cells from Rgs6(-/-) and Gbeta5(-/-) mice, suggest that the
      partial rescue of phenotypes in Rgs4(-/-):Rgs6(-/-) mice is attributable to
      another R7 RGS protein whose influence on M2R-IKACh signaling is masked by RGS4.
      Thus, RGS6-Gbeta5, but not RGS4, is the primary RGS modulator of parasympathetic
      HR regulation and SAN M2R-IKACh signaling in mice. 

PMID- 24318882
TI  - Identification of regulatory RNA in bacterial genomes by genome-scale mapping of
      transcription start sites.
AB  - The ability to map transcription start sites is critical for studies of gene
      regulation and for identification of novel RNAs. Conventional RNA-seq is often
      insufficient for identification of transcription start sites due to low coverage
      and/or RNA processing events. We have developed a highly sensitive, genome-scale
      method for detection of transcription start sites in bacteria. This method uses
      deep sequencing of cDNA libraries to identify transcription start sites with
      strand specificity at nucleotide resolution. Here, we describe the application of
      this method for transcription start site identification in Escherichia coli. 

PMID- 24318883
TI  - Screening inhibitory potential of anti-HIV RT RNA aptamers.
AB  - Aptamers targeted to HIV reverse transcriptase (RT) have been demonstrated to
      inhibit RT in biochemical assays and as in cell culture. However, methods
      employed to date to evaluate viral suppression utilize time-consuming serial
      passage of infectious HIV in aptamer-expressing stable cell lines. We have
      established a rapid, transfection-based assay system to effectively examine the
      inhibitory potential of anti-HIV RT aptamers expressed between two catalytically
      inactive hammerhead ribozymes. Our system can be altered and optimized for a
      variety of cloning schemes, and addition of sequences of interest to the cassette
      is simple and straightforward. When paired with methods to analyze aptamer RNA
      accumulation and localization in cells and as packaging into pseudotyped virions,
      the method has a very high level of success in predicting good inhibitors. 

PMID- 24318881
TI  - Hepatic apolipoprotein M (apoM) overexpression stimulates formation of larger
      apoM/sphingosine 1-phosphate-enriched plasma high density lipoprotein.
AB  - Apolipoprotein M (apoM), a lipocalin family member, preferentially associates
      with plasma HDL and binds plasma sphingosine 1-phosphate (S1P), a signaling
      molecule active in immune homeostasis and endothelial barrier function. ApoM
      overexpression in ABCA1-expressing HEK293 cells stimulated larger nascent HDL
      formation, compared with cells that did not express apoM; however, the in vivo
      role of apoM in HDL metabolism remains poorly understood. To test whether hepatic
      apoM overexpression increases plasma HDL size, we generated hepatocyte-specific
      apoM transgenic (APOM Tg) mice, which had an ~3-5-fold increase in plasma apoM
      levels compared with wild-type mice. Although HDL cholesterol concentrations were
      similar to wild-type mice, APOM Tg mice had larger plasma HDLs enriched in apoM,
      cholesteryl ester, lecithin:cholesterol acyltransferase, and S1P. Despite the
      presence of larger plasma HDLs in APOM Tg mice, in vivo macrophage reverse
      cholesterol transport capacity was similar to that in wild-type mice. APOM Tg
      mice had an ~5-fold increase in plasma S1P, which was predominantly associated
      with larger plasma HDLs. Primary hepatocytes from APOM Tg mice generated larger
      nascent HDLs and displayed increased sphingolipid synthesis and S1P secretion.
      Inhibition of ceramide synthases in hepatocytes increased cellular S1P levels but
      not S1P secretion, suggesting that apoM is rate-limiting in the export of
      hepatocyte S1P. Our data indicate that hepatocyte-specific apoM overexpression
      generates larger nascent HDLs and larger plasma HDLs, which preferentially bind
      apoM and S1P, and stimulates S1P biosynthesis for secretion. The unique apoM/S1P
      enriched plasma HDL may serve to deliver S1P to extrahepatic tissues for
      atheroprotection and may have other as yet unidentified functions. 

PMID- 24318884
TI  - Design and evaluation of clinically relevant SOFA-HDV ribozymes targeting HIV
      RNA.
AB  - Nucleic acid therapies targeting HIV replication have the potential to be used in
      conjunction with or in place of the standard small-molecule therapies. Among the
      different classes of nucleic acid therapies, several ribozymes (Rzs, RNA enzymes)
      have been developed to target HIV RNA. The design of Rzs targeting HIV RNA is
      complicated by the sequence diversity of viral strains and the structural
      diversity of their target sites. Using the SOFA-HDV Rz as an example, this
      chapter describes methods that can be used to design Rzs for controlling HIV
      replication. We describe how to (1) identify highly conserved Rz target sites in
      HIV RNA; (2) generate a set of Rzs with the potential to be used as therapeutics;
      and (3) screen these Rzs for activity against HIV production. 

PMID- 24318885
TI  - Directing RNase P-mediated cleavage of target mRNAs by engineered external guide
      sequences in cultured cells.
AB  - Ribonuclease P (RNase P) complexed with external guide sequence (termed as EGS)
      represents a novel nucleic acid-based gene interference approach to modulate gene
      expression. In previous studies, by using an in vitro selection procedure, we
      have successfully generated EGS variants that are complementary to target mRNAs,
      and these variants exhibit higher efficiency in directing human RNase P to cleave
      the target mRNAs than those derived from nature RNAs in vitro. This chapter
      describes the procedure of using engineered EGSs for in vitro trans-cleavage of
      target viral mRNAs in cultured cells. Detailed information is focused on (1)
      generation and in vitro cleavage assay of the customized EGS variants and (2)
      stable expression of EGS and evaluation of its activity in inhibition of viral
      gene expression and growth in cultured cells. These methods should provide
      general guidelines for using engineered EGS to direct RNase P-mediated cleavage
      of target mRNAs in cultured cells. 

PMID- 24318886
TI  - Design and analysis of hammerhead ribozyme activity against an artificial gene
      target.
AB  - In vitro cleavage assays are routinely conducted to properly assess the catalytic
      activity of hammerhead ribozymes (HHR) against target RNA molecules like dengue
      virus RNA. These experiments are performed for initial assessment of HHR
      catalysis in a cell-free system and have been simplified by the substitution of
      agarose gel electrophoresis for SDS-PAGE. Substituting mobility assays enables
      the analysis of ribozymes in a more rapid fashion without radioisotopes. Here we
      describe the in vitro transcription of an HHR and corresponding target from T7
      promoted plasmids into RNA molecules leading to the analysis of HHR activity
      against the RNA target by in vitro cleavage assays. 

PMID- 24318887
TI  - Knockdown strategies for the study of proprotein convertases and proliferation in
      prostate cancer cells.
AB  - Gene silencing strategies targeting mRNA are suitable methods to validate the
      functions of specific genes. In this chapter, we sought to compare two knockdown
      strategies for the study of proprotein convertases and proliferation in prostate
      cancer cells. We used both SOFA-HDV ribozyme and lentiviral-mediated shRNA
      delivery system to reduce PACE4 mRNA levels and validate its implication in the
      proliferation of DU145 prostate cancer cells. The cellular effects of PACE4
      knockdown were assessed (1) in vitro using two tetrazolium salts (MTT and XTT
      assays) and (2) in vivo using a tumor xenograft approach in immunodeficient mice
      (Nu/Nu). Our results confirm the unique role of the proprotein convertase PACE4
      in prostate cancer cell proliferation while demonstrating advantages and
      disadvantages of each approach. Achieving target validation in an effective
      manner is critical, as further development using a drug development approach is
      highly laborious and requires enormous resources. 

PMID- 24318889
TI  - Characterization of hairpin ribozyme reactions.
AB  - Hairpin ribozymes are small RNA catalytic motifs naturally found in the satellite
      RNAs of tobacco ringspot virus (TRsV), chicory yellow mottle virus (CYMoV), and
      arabis mosaic virus (ArMV). The catalytic activity of the hairpin ribozyme
      extends to both cleavage and ligation reactions. Here we describe methods for the
      kinetic analysis of the self-cleavage reaction under transcription reaction
      conditions. We also describe methods for the generation of DNA templates for
      subsequent in vitro transcription reaction of hairpin ribozymes. This is followed
      by a description of the preparation of the suitable RNA molecules for ligation
      reaction and their kinetic analysis. 

PMID- 24318888
TI  - Use of tumor-targeting trans-splicing ribozyme for cancer treatment.
AB  - One of the major concerns with regard to successful cancer gene therapy is to
      enhance both efficacy and safety. Gene targeting may represent an attractive tool
      to combat cancer cells without damage to normal cells. Here, we introduce a tumor
      targeting approach with the Tetrahymena group I intron-based trans-splicing
      ribozyme, which cleaves target RNA and trans-ligate an exon tagged at the end of
      the ribozyme onto the downstream U nucleotide of the cleaved target RNA. We
      develop a specific trans-splicing ribozyme that can target and reprogram human
      cytoskeleton-associate protein 2 (hCKAP2)-encoding RNA to trigger therapeutic
      transgene herpes simplex virus thymidine kinase (HSVtk) selectively in cancer
      cells that express the RNA. Adenoviral vectors encoding the hCKAP2-specific trans
      splicing ribozyme are constructed for in vivo delivery into either subcutaneous
      tumor xenograft or orthotopically multifocal hepatocarcinoma. We present analyses
      of the efficacy of the recombinant adenoviral vectors in terms of cancer
      retardation, target RNA and cell specificity, and in vivo toxicity. 

PMID- 24318890
TI  - Finding instances of riboswitches and ribozymes by homology search of structured
      RNA with Infernal.
AB  - In the genomics era, computational tools are essential to extract information
      from sequences and annotate them to allow easy access to genes. Fortunately, many
      of these tools are now part of standard pipelines. As a consequence, a cornucopia
      of genomic features is available in multiple databases. Nevertheless, as novel
      genomes are sequenced and new structured RNAs are discovered, homology searches
      and additional analyses need to be performed. In this chapter, we propose simple
      ways of finding instances of riboswitches and ribozymes in databases or in
      unannotated genomes, as well as ways of finding variants that deviate from the
      typical consensus. 

PMID- 24318891
TI  - Structure-based virtual screening for the identification of RNA-binding ligands.
AB  - Structure-based virtual screening exploits the 3D structure of the target as a
      template for the discovery of new ligands. It is a key method for hit discovery
      and was originally developed for protein targets. Recently, this method has also
      been applied to RNA targets. This chapter gives an overview of this method and
      its application in the context of ligand discovery for RNA. In addition, it
      describes in detail how to conduct virtual screening for RNA targets, making use
      of software that is free for noncommercial use. Some advice on how to avoid
      common pitfalls in virtual screening is also given. 

PMID- 24318892
TI  - Probing riboswitch binding sites with molecular docking, focused libraries, and
      in-line probing assays.
AB  - Molecular docking calculations combined with chemically focused libraries can
      bring insight in the exploration of the structure-activity relationships for a
      series of related compounds against an RNA target. Yet, the in silico engine must
      be fueled by experimental observations to drive the research into a more
      effective ligand-discovery path. Here we show how molecular docking predictions
      can be coupled with in-line probing assays to explore the available chemical and
      configurational space in a riboswitch binding pocket. 

PMID- 24318893
TI  - Discovery of small molecule modifiers of microRNAs for the treatment of HCV
      infection.
AB  - While RNA has traditionally been viewed as a mechanism to transfer genetic
      information, its importance and functionality has only truly been demonstrated in
      the past 20 years. One prime example of this significance can be found within
      microRNAs (miRNAs), which are involved in the regulation of a substantial number
      of human genes. Consequently, these miRNAs represent a novel target for
      therapeutic agents towards the treatment of a variety of diseases and disorders.
      Specifically, misregulation of miR-122 has been demonstrated to be relevant in
      the cellular propagation of Hepatitis C (HCV), and thus modulators of miR-122 can
      have a substantial effect on viral loads. This protocol describes the development
      of an assay for the discovery of small molecule regulators of miR-122, and
      ultimately HCV therapeutics. Due to the excellent pharmacokinetic properties of
      small molecule libraries, these regulators represent a substantial advantage over
      traditional antisense agents. 

PMID- 24318894
TI  - Bacterial flavin mononucleotide riboswitches as targets for flavin analogs.
AB  - Roseoflavin is a toxic riboflavin (vitamin B2) analog and naturally is produced
      by Streptomyces davawensis. Roseoflavin is converted to roseoflavin
      mononucleotide (RoFMN) by promiscuous flavokinases (EC 2.7.1.26). Flavin
      mononucleotide (FMN) riboswitches control the expression of genes involved in
      riboflavin biosynthesis and/or transport. RoFMN triggers FMN riboswitches and
      negatively (or positively) affects expression of the downstream genes. RoFMN
      binding to the aptamer portion of FMN riboswitch RNAs occurs in the course of
      transcription by cellular RNA polymerases. We developed an in vitro test system
      to functionally characterize the interaction between riboflavin/FMN analogs such
      as roseoflavin/RoFMN and FMN riboswitches in the context of an actively
      transcribing RNA polymerase. 

PMID- 24318895
TI  - Construction and application of riboswitch-based sensors that detect metabolites
      within bacterial cells.
AB  - A riboswitch is an RNA element that detects the level of a specific metabolite
      within the cell and regulates the expression of co-transcribed genes. By fusing a
      riboswitch to a reporter protein in a carefully designed and tested construct,
      this ability can be exploited to create an intracellular sensor that detects the
      level of a particular small molecule within live bacterial cells. There is a
      great deal of flexibility in the design of such a sensor and factors such as the
      molecule to be detected and the downstream experiments in which the sensor will
      be applied should guide the specific blueprint of the final construct. The
      completed sensor plasmid needs to be rigorously tested with appropriate controls
      to ensure that its dynamic range, signal strength, sensitivity and specificity
      are suitable for its intended applications. In this chapter, methods for the
      design, assessment and use of riboswitch sensors are provided along with those
      for one example application for which riboswitch sensors are ideally suited. 

PMID- 24318896
TI  - Screening assays to identify artificial glmS ribozyme activators.
AB  - Ribsowitches are putative drug targets as they often regulate the expression of
      essential bacterial genes. This finding necessitates the development of suitable
      assays, at best high-throughput (HT) compatible, which allow the screening of
      compound libraries for riboswitch activation. Here, we describe a HT-compatible
      fluorescence-based screening assay employing a minimal core motif of the Bacillus
      subtilis glmS riboswitch and the metabolite-induced self-cleavage assay using the
      full-length glmS ribozyme of Staphylococcus aureus for the identification of
      artificial molecules activating this regulatory RNA. 

PMID- 24318897
TI  - Analysis of riboswitch structure and ligand binding using small-angle X-ray
      scattering (SAXS).
AB  - Small-angle X-ray scattering (SAXS) is a powerful tool for examining the global
      conformation of riboswitches in solution, and how this is modulated by binding of
      divalent cations and small molecule ligands. SAXS experiments, which typically
      require only minutes per sample, directly yield two quantities describing the
      size and shape of the RNA: the radius of gyration (Rg) and the maximum linear
      dimension (Dmax). Examination of these quantities can reveal if a riboswitch
      undergoes cation-induced compaction. Comparison of the Rg and Dmax values between
      samples containing different concentrations of ligand reveals the overall
      structural response of the riboswitch to ligand. The Kratky plot (a graphical
      representation that emphasizes the higher-resolution SAXS data) and the P(r) plot
      or pair-probability distribution (an indirect Fourier transform, or power
      spectrum of the data) can provide additional evidence of riboswitch
      conformational changes. Simulation methods have been developed for generating
      three-dimensional reconstructions consistent with the one-dimensional SAXS data.
      These low-resolution molecular envelopes can aid in deciphering the relative
      helical arrangement within the RNA.

PMID- 24318898
TI  - Use of SHAPE to select 2AP substitution sites for RNA-ligand interactions and
      dynamics studies.
AB  - Most regulatory RNA molecules must adopt a precise secondary fold and tertiary
      structure to allow their function in cells. A number of experimental approaches,
      such as the 2-Aminopurine-Based RNA Folding Analysis (2ApFold), have therefore
      been developed to offer insights into the folding and folding dynamics of RNA. A
      crucial requirement for this method is the selection of proper 2AP labeling
      positions. In that regard, we recently discovered that Selective 2'-Hydroxyl
      Acylation analyzed by Primer Extension (SHAPE) offers a reliable path to identify
      appropriate nucleotides for 2AP substitution on a target RNA. This chapter
      describes the straightforward procedure to select 2AP substitution sites in RNA
      molecules using SHAPE probing. The protocols detail the preparation of the target
      RNA by transcription, and the SHAPE steps including (1) probing of the RNA, (2)
      reverse transcription with a radiolabeled primer, (3) sequencing gel, and (4)
      analysis of the obtained band pattern. 

PMID- 24318899
TI  - Cell internalization SELEX: in vitro selection for molecules that internalize
      into cells.
AB  - Aptamer technology allows for the selection of nucleic acids that can bind to and
      enter cells. By establishing conditions during the selection that eliminate cell
      surface binders as well as non-internalizing RNAs, only extremely tightly bound
      aptamers or aptamers that have internalized are recovered. We describe a general
      scheme for selecting RNA molecules that are capable of internalizing into cells
      and discuss the factors that can affect a successful selection. Much like
      standard cell-surface selections, these types of selections should be possible
      independent of detailed knowledge of the cell surface. 

PMID- 24318900
TI  - DNA electronic switches based on analyte-responsive aptamers.
AB  - Aptamers have proven to be very useful as high-affinity and -specificity
      molecular recognition elements in analytical sensors of various forms. Herein, we
      describe a general process for creating an aptamer-based sensor that functions as
      an analyte-responsive, nano-sized, electronic switch. These sensors can provide
      an electrochemical readout, by switching through-DNA charge transfer across a DNA
      three-way junction from "off" to "on" in response to the binding of a target
      ligand to the sensor's aptamer domain. We detail the general design principles
      for such sensors, as well as the biochemical charge transfer assays used to
      identify functional sensors. In these gel electrophoresis-based assays, analyte
      responsive conductivity switching is detected conveniently through biochemical
      experiments that characterize oxidative DNA damage patterns in sequencing PAGE
      gels. 

PMID- 24318901
TI  - Phase II trial of combination nab-paclitaxel, carboplatin and gemcitabine in
      first line therapy of advanced urothelial carcinoma.
AB  - BACKGROUND: Paclitaxel has significant single agent activity in urothelial
      cancer. The 130 nm albumin bound paclitaxel (nab-paclitaxel, ABI-007) delivers
      more paclitaxel to tumor than conventional paclitaxel without cremophor related
      toxicities. We assessed the efficacy of nab-paclitaxel in combination with
      carboplatin and gemcitabine as first line therapy in advanced urothelial cancer.
      METHODS: Eligible patients had histologically confirmed metastatic, locally
      recurrent or advanced pure or mixed urothelial cancer, ECOG performance status of
      0-2, no prior chemotherapy for current disease stage and no taxane for >= 1 year.
      Therapy consisted of nab-paclitaxel at 220 mg/m2 intravenously with optional dose
      escalation to 260 mg/m2 for subsequent cycles, with carboplatin AUC 5 on day 1
      and gemcitabine at 800 mg/m2 on days 1 and 8 in 21-day cycles. Dose modifications
      in all three drugs to -1 and -2 levels were allowed for toxicity. Primary
      endpoint was overall response rate by RECIST 1.0. Secondary endpoints were
      safety, progression free and overall survival. Using a two-stage design, 32
      patients were planned to be enrolled. RESULTS: Due to poor accrual only 16
      patients were enrolled. Thirteen patients had metastatic disease, 3 were women,
      and median age was 73.9 years (range 51.3-83). ECOG PS was 0 in 4 (25.0 %) and 1
      in 11 (68.8 %) patients. Creatinine clearance by Cockroft-Gault formula was less
      than 60 in 43 % of patients and 50 % of patients had visceral disease at
      baseline. The regimen was associated with severe toxicity, mainly cytopenias.
      Adverse events required removal of 11 patients (68.8 %) from study. Seven
      patients (43.7 %) missed >= 1 dose due to toxicity and 7 patients were reduced to
      -2 dose level. Nine (56.4 %) grade >= 3 neutropenia and thrombocytopenia each but
      only 1 episode of febrile neutropenia (6.3 %) was reported. Grade >= 3 anemia was
      noted in 6 patients (37.5 %). Grade 2 neuropathy was seen in 12.5 % but no grade
      >= 3 neuropathy was observed. One patient had confirmed PR (6.7 %; 95 % CI, 0-32
      %) and 2 (13.3 %) had unconfirmed PR. Six other patients (40 %) had SD. Due to
      censoring at study exit due to adverse events before true progression, median PFS
      was 11.2 months (95 % CI,2.0-11.2 m). Median overall survival was 13.1 months (95
      % CI, 9.8-19.6 m). CONCLUSIONS: The combination of nab-paclitaxel, carboplatin
      and gemcitabine was poorly tolerated in this high risk patient population at
      these doses and schedule. Other nab-paclitaxel based combinations should be
      explored in first line therapy of advanced urothelial cancer.

PMID- 24318903
TI  - Comparative study by electrophysiology of olfactory responses in bumblebees
      (Bombus hypnorum andBombus terrestris).
AB  - Electrophysiological data (EAG) were recorded on adult bumblebees stimulated with
      floral and/or pheromonal pure odorants at different concentrations. The responses
      of queen, worker, and male bees are compared and the sensitivities of these
      insects to the pure odorants tested are discussed. 

PMID- 24318902
TI  - MiR-139 targets CXCR4 and inhibits the proliferation and metastasis of laryngeal
      squamous carcinoma cells.
AB  - Our previous studies have showed that chemokine receptor 4 (CXCR4) was over
      expressed in laryngeal squamous cell carcinoma (LSCC). However, the mechanism
      underlying aberrant CXCR4 expression remains unclear. To investigate the roles
      played by miRNAs in CXCR4 over-expression in LSCC, putative miR-139 was predicted
      through computational algorithms, including TargetScan, PicTar and miRBase, and
      luciferase reporter assay was explored to confirm that whether CXCR4 was directly
      regulated by miR-139. Then, quantitative real-time PCR, immunohistochemistry and
      in situ hybridization methods were employed to detect the expression of miR-139
      and CXCR4 in primary LSCC tissues, normal adjacent mucosal tissues and metastatic
      lesions derived from 40 LSCC patients in the Second Hospital, Xi'An JiaoTong
      University. Finally, gain- and loss-of-function assays were adopted to explore
      the effects of miR-139 and CXCR4 on proliferation, invasion and metastasis of the
      human LSCC cell line Hep-2 in vitro and in vivo. Our results showed that miR-139
      dampened CXCR4 expression, and CXCR4 was directly targeted by miR-139.
      Additionally, the expression of miR-139 was reduced in alignment with the
      progression of primary to metastatic LSCC. Moreover, an inverse correlation was
      observed between miR-139 and CXCR4 protein levels in LSCC specimens. Functional
      analyses demonstrated that ectopic expression of miR-139 inhibited cell
      proliferation, migration and metastasis of Hep-2 cells in vitro and in vivo.
      Similar to the observations seen in restoring miR-139 expression, dampening of
      CXCR4 expression inhibited cell growth, migration and invasion, whereas miR-139
      over-expression reversed the pro-metastatic effect of CXCR4. Taken together, we
      conclude that miR-139 targets CXCR4 and inhibits proliferation and metastasis of
      LSCC.

PMID- 24318904
TI  - Effects of ferulic acid and some of its microbial metabolic products on radicle
      growth of cucumber.
AB  - An initial survey of the effects of aqueous solutions of ferulic acid and three
      of its microbial metabolic products at pH 4.5, 6.0, and 7.5 was determined on
      radicle growth of 11 crop species in Petri dishes. These bioassays indicated that
      cucumber, ladino clover, lettuce, mung bean, and wheat were inhibited by ferulic,
      caffeic, protocatechuic, and/or vanillic acids and that the magnitude of
      inhibition varied with concentration (0-2 mM), phenolic acid, and pH of the
      initial solution. The pH values of the initial solutions changed considerably
      when added to the Petri dishes containing filter paper and seeds. The final pH
      values after 48 hr were 6.6, 6.8, and 7.1, respectively, for the initial 4.5,
      6.0, and 7.5 pH solutions. The amounts of the phenolic acids in the Petri dishes
      declined rapidly over the 48 hr of the bioassay, and the rate of phenolic acid
      decline was species specific. Cucumber was subsequently chosen as the bioassay
      species for further study. MES buffer was used to stabilize the pH of the
      phenolic acid solutions which ranged between 5.5 and 5.8 for all subsequent
      studies. Inhibition of radicle growth declined in a curvilinear manner over the 0
      2 mM concentration range. At 0.125 and 0.25 mM concentrations of ferulic acid,
      radicle growth of cucumber was inhibited 7 and 14%, respectively. A variety of
      microbial metabolic products of ferulic acid was identified in the Petri dishes
      and tested for toxicity. Only vanillic acid was as inhibitory as ferulic acid.
      The remaining phenolic acids were less inhibitory to noninhibitory. When mixtures
      of phenolic acids were tested, individual components were antagonistic to each
      other in the inhibition of cucumber radicle growth. Depending on the initial
      total concentration of the mixture, effects ranged from 5 to 35% lower than the
      sum of the inhibition of each phenolic acid tested separately. Implications of
      these findings to germination bioassays are discussed. 

PMID- 24318905
TI  - Sex pheromone source location by garter snakes: : A mechanism for detection of
      direction in nonvolatile trails.
AB  - Male plains garter snakes,Thamnophis radix, tested in a 240-cm-long arena can
      detect directional information from a female pheromone trail only when the female
      is allowed to push against pegs while laying the trail. The female's normal
      locomotor activity apparently deposits pheromone on the anterolateral surfaces of
      vertical structures in her environment. The male sensorily assays the sides of
      these objects and from this information determines the female's direction of
      travel. 

PMID- 24318906
TI  - Structure-activity relationships among aromatic analogs of trail-following
      pheromone of subterranean termites.
AB  - A series of 12 substituted (Z)-4-phenyl-3-buten-l-ol (PBO) derivatives were
      synthesized and evaluated for trail-following activity in five species of
      subterranean termites in the generaCoptotermes, Prorhinotermes, Reticulitermes,
      andSchedorhinotermes (Isoptera: Rhinotermitidae). The unsubstituted parent PBO
      was the most active for all species, and electron-withdrawing and electron
      donating groups both reduced potency. Sensitivity to substitution in the ortho
      position suggests steric inhibition of binding by the 2'-substituted analogs.
      Different sensitivities to these pheromone analogs were found among the five
      species, withR.flavipes andS. lamanianus showing the highest level of trail
      following activity for the PBO analogs. 

PMID- 24318907
TI  - Interspecific variation of diterpene composition ofCubitermes soldier defense
      secretions.
AB  - Soldiers of the humivorous termite generaCubitermes andCrenetermes (Isoptera:
      Termitidae: Termitinae) secrete a mixture of unusual diterpene hydrocarbons from
      the fontanellar opening of the frontal gland. The defense secretions of
      sixCubitermes species and oneCrenetermes species show species-specific
      distributions of the five chemically identified major components and 12
      unidentified minor components. The secretion is also present with its characteric
      terpene distribution in white presoldiers and newly molted soldiers, but is
      completely absent in workers. 

PMID- 24318908
TI  - (5Z,9Z)-3-alkyl-5-methylindolizidines fromSolenopsis (Diplorhoptrum) species.
AB  - The alkaloidal venom components of two species of thief ants,Solenopsis
      (Diplorhoptrum) species AA andS. (Diplorhoptrum)conjurata have been found to
      contain (5Z,9Z)-3-hexyl-5-methylindolizidine and a mixture of (5Z,9Z)-3-ethyl-5
      methylindolizidine andcis-2-methyl-6-nonyl-piperidine,trans-2-methyl-6
      nonylpiperidine,cis-2-methyl-6-undecylpiperidine, and hexadecanoic
      acid.Monomorium pharaonis was similarly investigated and found to contain the
      indolizidine and pyrrolidines previously described (Ritter et al., 1977b). Both
      indolizidines were synthesized along with their stereoisomers and separated by
      preparative gas chromatography. Spectral studies revealed the stereochemistry to
      be 5Z,9Z in both cases. The stereochemistry of 2-butyl-5-pentylpyrrolidine inM.
      phaeronis has also been established. Biosynthetic relationships are discussed. 

PMID- 24318909
TI  - Isolation and identification of cotton synomones mediating searching behavior by
      parasitoidCampoletis sonorensis.
AB  - In laboratory bioassays, the parasitoidCampoletis sonorensis was attracted to the
      following sesquiterpenes isolated from cotton essential oil: alpha-humulene,
      gamma-bisabolene, beta-caryophyllene oxide, spathulenol, beta-bisabolol, and a
      new, naturally occurring bisabolene-related alcohol, (2-p-tolyl-6-methylhept-5-en
      2-ol) which we name gossonorol. This is the first report of spathulenol in
      cotton. beta-Caryophyllene, a major component of cotton, was not attractive to
      the parasitoids. The response of the parasitoids to these compounds and the
      possibility of augmenting parasitoid activity in the field by manipulating plant
      secondary metabolites is discussed. 

PMID- 24318910
TI  - ACaenorhabditis elegans dauer-inducing pheromone and an antagonistic component of
      the food supply.
AB  - The free-living soil nematodeCaenorhabditis elegans forms a nonfeeding dispersal
      stage at the second molt called the dauer larva when exposed to environmental
      cues indicating crowding and limited food. An improved bioassay, tenfold more
      sensitive than that used previously, has been used in the characterization of the
      two chemical cues which act competitively in controlling this developmental
      process. The pheromone concentration provides a measure of the population
      density; it enhances dauer larva formation, and inhibits recovery (exit) from the
      dauer stage. The pheromone is a family of related molecules which are
      nonvolatile, very stable, and possess physical and Chromatographie properties
      similar to those of hydroxylated fatty acids and bile acids. A food signal, with
      effects on development opposite those of the pheromone, is produced by bacteria,
      and is also present in yeast extract. In contrast to the pheromone, the food
      signal is a labile substance which is neutral and hydrophilic. 

PMID- 24318911
TI  - Experimental design and ecological realism.

PMID- 24318912
TI  - Theory and practice in crayfish communication studies.

PMID- 24318913
TI  - Chemical communication in crayfish: : Physiological ecology, realism and
      experimental design.

PMID- 24318914
TI  - Errata.

PMID- 24318915
TI  - Nonlinear distortion correction of diffusion MR images improves quantitative DTI
      measurements in glioblastoma.
AB  - The purpose of this study was to use a retrospective nonlinear distortion
      correction technique and evaluate the changes in DTI metrics in areas of interest
      in and around GBM tumors. A total of 24 histologically confirmed GBM patients
      with pre-operative 20-direction DTI scans were examined. Variability in apparent
      diffusion coefficient (ADC) and fractional anisotropy (FA) in normal tissue
      before and after distortion correction were examined. Changes in mean, median and
      variance of ADC and FA in contrast enhancing and T2/FLAIR ROIs were also examined
      with and without distortion correction. Results suggest the intra-subject SDs of
      ADC and FA decreased in normal tissue after the application of distortion
      correction (P < 0.0001). FA mean and median values decreased after distortion
      correction in both T1+C and T2 ROIs (P < 0.017), while ADC mean and median values
      did not significantly change except for the median ADC in T1+C ROIs (P = 0.0054).
      The intra-subject SD of ADC and FA values in tumor ROIs changed significantly
      with distortion correction, and Bland-Altman analysis indicated that the bias and
      the SD of the bias of these intra-subject SDs were larger than those of the mean
      and median terms. Additionally, the means of the two curves of a double Gaussian
      fit to the histogram of ADC values from T1+C ROIs, ADCL (mean of lower Gaussian)
      as well as ADCH (mean of the higher Gaussian) were found to change significantly
      with distortion correction (P = 0.0045 for ADCL and P = 0.0370 for ADCH).
      Nonlinear distortion correction better aligns neuro-anatomical structures between
      DTI and anatomical scans, and significantly alters the measurement of values
      within tumor ROIs for GBM patients. 

PMID- 24318916
TI  - Market-level assessment of the economic benefits of atrazine in the United
      States.
AB  - BACKGROUND: Atrazine and other triazine herbicides are widely used in US maize
      and sorghum production, yet the most recent market-level assessment of the
      economic benefits of atrazine is for market conditions prevalent in the early
      1990s, before commercialization of transgenic crops. Grain markets have changed
      substantially since that time; for example, the size of the US maize market
      increased by 170% from 1990-1992 to 2007-2009. This paper reports a current
      assessment of the economic benefits of atrazine. RESULTS: Yield increases and
      cost changes implied by triazine herbicides are projected to reduce maize prices
      by 7-8% and sorghum prices by 19-20%. Projected consumer benefits from lower
      prices range from $US 3.6 to 4.4 * 10(9) annually, with the net projected
      economic benefit for triazine herbicides to the US economy ranging from $US 2.9
      to 3.4 * 10(9) annually because lower prices imply reduced producer income.
      Productivity gains from triazine herbicides maintain an estimated 270 000-390 000
      ha of land in non-crop uses that generate environmental benefits not accounted
      for in this analysis. CONCLUSION: Even in the current era, with transgenic
      varieties dominating crop production, atrazine and the other triazine herbicides
      continue to be a key part of maize and sorghum production and generate
      substantial economic benefits.

PMID- 24318917
TI  - Multilevel structural characteristics for the natural substrate proteins of
      bacterial small heat shock proteins.
AB  - Small heat shock proteins (sHSPs) are ubiquitous molecular chaperones that
      prevent the aggregation of various non-native proteins and play crucial roles for
      protein quality control in cells. It is poorly understood what natural substrate
      proteins, with respect to structural characteristics, are preferentially bound by
      sHSPs in cells. Here we compared the structural characteristics for the natural
      substrate proteins of Escherichia coli IbpB and Deinococcus radiodurans Hsp20.2
      with the respective bacterial proteome at multiple levels, mainly by using
      bioinformatics analysis. Data indicate that both IbpB and Hsp20.2 preferentially
      bind to substrates of high molecular weight or moderate acidity. Surprisingly,
      their substrates contain abundant charged residues but not abundant hydrophobic
      residues, thus strongly indicating that ionic interactions other than hydrophobic
      interactions also play crucial roles for the substrate recognition and binding of
      sHSPs. Further, secondary structure prediction analysis indicates that the
      substrates of low percentage of beta-sheets or coils but high percentage of alpha
      helices are un-favored by both IbpB and Hsp20.2. In addition, IbpB preferentially
      interacts with multi-domain proteins but unfavorably with alpha + beta proteins
      as revealed by SCOP analysis. Together, our data suggest that bacterial sHSPs,
      though having broad substrate spectrums, selectively bind to substrates of
      certain structural features. These structural characteristic elements may
      substantially participate in the sHSP-substrate interaction and/or increase the
      aggregation tendency of the substrates, thus making the substrates more
      preferentially bound by sHSPs.

PMID- 24318919
TI  - University rankings and medical physics.

PMID- 24318918
TI  - Naive and memory CD8 T cell pool homeostasis in advanced aging: impact of age and
      of antigen-specific responses to cytomegalovirus.
AB  - Alterations in the circulating CD8+ T cell pool, with a loss of naive and
      accumulation of effector/effector memory cells, are pronounced in older adults.
      However, homeostatic forces that dictate such changes remain incompletely
      understood. This observational cross-sectional study explored the basis for
      variability of CD8+ T cell number and composition of its main subsets: naive,
      central memory and effector memory T cells, in 131 cytomegalovirus (CMV)
      seropositive subjects aged over 60 years. We found great heterogeneity of CD8+ T
      cell numbers, which was mainly due to variability of the CD8 + CD28- T cell
      subset regardless of age. Analysis, by multiple regression, of distinct factors
      revealed that age was a predictor for the loss in absolute number of naive T
      cells, but was not associated with changes in central or effector memory CD8+ T
      cell subsets. By contrast, the size of CD8+ T cells specific to pp65 and IE-1
      antigens of CMV, predicted CD28 - CD8+ T cell, antigen-experienced CD8+ T cell,
      and even total CD8+ T cell numbers, but not naive CD8+ T cell loss. These results
      indicate a clear dichotomy between the homeostasis of naive and antigen
      experienced subsets of CD8+ T cells which are independently affected, in human
      later life, by age and antigen-specific responses to CMV, respectively. 

PMID- 24318920
TI  - Electron transport and photophosphorylation by Photosystem I in vivo in plants
      and cyanobacteria.
AB  - Recently, a number of techniques, some of them relatively new and many often used
      in combination, have given a clearer picture of the dynamic role of electron
      transport in Photosystem I of photosynthesis and of coupled cyclic
      photophosphorylation. For example, the photoacoustic technique has detected
      cyclic electron transport in vivo in all the major algal groups and in leaves of
      higher plants. Spectroscopic measurements of the Photosystem I reaction center
      and of the changes in light scattering associated with thylakoid membrane
      energization also indicate that cyclic photophosphorylation occurs in living
      plants and cyanobacteria, particularly under stressful conditions.In
      cyanobacteria, the path of cyclic electron transport has recently been proposed
      to include an NAD(P)H dehydrogenase, a complex that may also participate in
      respiratory electron transport. Photosynthesis and respiration may share common
      electron carriers in eukaryotes also. Chlororespiration, the uptake of O2 in the
      dark by chloroplasts, is inhibited by excitation of Photosystem I, which diverts
      electrons away from the chlororespiratory chain into the photosynthetic electron
      transport chain. Chlororespiration in N-starved Chlamydomonas increases ten fold
      over that of the control, perhaps because carbohydrates and NAD(P)H are oxidized
      and ATP produced by this process.The regulation of energy distribution to the
      photosystems and of cyclic and non-cyclic phosphorylation via state 1 to state 2
      transitions may involve the cytochrome b 6-f complex. An increased demand for ATP
      lowers the transthylakoid pH gradient, activates the b 6-f complex, stimulates
      phosphorylation of the light-harvesting chlorophyll-protein complex of
      Photosystem II and decreases energy input to Photosystem II upon induction of
      state 2. The resulting increase in the absorption by Photosystem I favors cyclic
      electron flow and ATP production over linear electron flow to NADP and 'poises'
      the system by slowing down the flow of electrons originating in Photosystem
      II.Cyclic electron transport may function to prevent photoinhibition to the
      photosynthetic apparatus as well as to provide ATP. Thus, under high light
      intensities where CO2 can limit photosynthesis, especially when stomates are
      closed as a result of water stress, the proton gradient established by coupled
      cyclic electron transport can prevent over-reduction of the electron transport
      system by increasing thermal de-excitation in Photosystem II (Weis and Berry
      1987). Increased cyclic photophosphorylation may also serve to drive ion uptake
      in nutrient-deprived cells or ion export in salt-stressed cells.There is evidence
      in some plants for a specialization of Photosystem I. For example, in the red
      alga Porphyra about one third of the total Photosystem I units are engaged in
      linear electron transfer from Photosystem II and the remaining two thirds of the
      Photosystem I units are specialized for cyclic electron flow. Other organisms
      show evidence of similar specialization.Improved understanding of the biological
      role of cyclic photophosphorylation will depend on experiments made on living
      cells and measurements of cyclic photophosphorylation in vivo. 

PMID- 24318921
TI  - Organization and transcription of the genes encoding two differentially expressed
      phycocyanins in the cyanobacterium Pseudanabaena sp. PCC 7409.
AB  - The cpc1 and cpc2 operons of the group III chromatically adapting cyanobacterium
      Pseudanabaena sp. PCC 7409 were isolated and their nucleotide sequences
      determined. The cpc1 operon consists of the genes cpcB1A1EF and gives rise to an
      abundant 1400-nucleotide transcript encoding the cpcB1A1 genes and two low
      abundance transcripts of 1000 nucleotides and 1100 nucleotides encoding the cpcF
      gene. Two extremely low-abundance transcripts of approximately 2900 nucleotides
      and 4800 nucleotides possibly encode cpcB1A1E and cpcB1A1EF, respectively. All
      transcripts were present in cultures grown in either red or green light. The
      transcription start of the cpcB1A1 mRNA was mapped to a position 238 bp 5' to the
      cpcB1 translation start. The cloned fragment containing the cpcB2A2 genes was
      found to contain only a portion of the cpc2 operon and consisted of the cpcB2A2
      genes and the 5' portion of the linker gene cpcH2. On the basis of biochemical
      evidence, as well as sequence data from other cpc operons, it is probable that
      the complete Pseudanabaena sp. PCC 7409 cpc2 operon consists of the genes
      cpcB2A2H2I2D2. This operon is almost exclusively transcribed in cells grown in
      red light and gives rise to an abundant mRNA 1400 nucleotides in length that
      encodes the cpcB2A2 genes. A second transcript of 2400 nucleotides encodes the
      cpcB2A2H2 genes. A third transcript of 3800 nucleotides encodes the cpcB2A2H2
      genes and probably the cpcI2 and cpcD2 genes as well. Transcription of the cpc2
      mRNAs inititates 219 bp 5' to the cpcB2 translation start. The promoter region of
      the Pseudanabaena sp. PCC 7409 cpc1 operon contains the sequence 5' ttGTATaa 3'
      that is also found to occur within 20 bp of the transcription initiation sites of
      a number of other constitutively expressed cpc promoters. A high level of
      sequence similarity also occurs between the red-light-inducible cpc2 promoters of
      Pseudanabaena sp. PCC 7409 and Calothrix sp. PCC 7601. 

PMID- 24318922
TI  - Phylogenetic analysis of photosynthetic genes of Rhodocyclus gelatinosus:
      Possibility of horizontal gene transfer in purple bacteria.
AB  - Nucleotide sequences of the genes coding for the M and cytochrome subunits of the
      photosynthetic reaction center of Rhodocyclus gelatinosus, a purple bacterium in
      the beta subdivision, were determined. The deduced amino acid sequences of these
      proteins were compared with those of other photosynthetic bacteria. Based on the
      homology of these two photosynthetic proteins, Rc. gelatinosus was placed in the
      alpha subdivision of purple bacteria, which disagrees with the phylogenetic trees
      based on 16S rRNA and soluble cytochrome c 2. Horizontal transfer of the genes
      which code for the photosynthetic apparatus in purple bacteria can be postulated
      if the phylogenetic trees based on 16S rRNA and soluble cytochrome c 2 reflect
      the real history of purple bacteria. 

PMID- 24318923
TI  - Simultaneous measurement of changes in red and blue fluorescence in illuminated
      isolated chloroplasts and leaf pieces: The contribution of NADPH to the blue
      fluorescence signal.
AB  - A newly developed nitrogen laser fluorimeter insensitive to actinic illumination
      was used to follow simultaneously the light induced changes in red and blue
      fluorescence of intact isolated spinach chloroplasts and leaf pieces. The
      recorded variable blue fluorescence was linked to a water soluble component of
      intact isolated chloroplasts, depended on Photosystem I, and was related to
      changes in carbon metabolism. From the comparison of changes in intact and broken
      chloroplasts and from fluorescence spectra under different conditions, it was
      concluded that the variation in NADPH was the major cause for the changes in blue
      fluorescence. This study opens a path towards continuous and non-destructive
      monitoring of NADPH redox state in chloroplasts and leaves. 

PMID- 24318924
TI  - The non-photochemical reduction of plastoquinone in leaves.
AB  - Although it is generally assumed that the plastoquinone pool of thylakoid
      membranes in leaves of higher plants is rapidly oxidized upon darkening, this is
      often not the case. A multiflash kinetic fluorimeter was used to monitor the
      redox state of the plastoquinone pool in leaves. It was found that in many
      species of plants, particularly those using the NAD-malic enzyme C4 system of
      photosynthesis, the pool actually became more reduced following a light to dark
      transition. In some Amaranthus species, plastoquinone remained reduced in the
      dark for several hours. Far red light, which preferentially drives Photosystem I
      turnover, could effectively oxidize the plastoquinone pool. Plastoquinone was re
      reduced in the dark within a few seconds when far red illumination was removed.
      The underlying mechanism of the dark reduction of the plastoquinone pool is still
      uncertain but may involve chlororespiratory activity. 

PMID- 24318925
TI  - Genome-wide gene expression effects of sex chromosome imprinting in Drosophila.
AB  - Imprinting is well-documented in both plant and animal species. In Drosophila,
      the Y chromosome is differently modified when transmitted through the male and
      female germlines. Here, we report genome-wide gene expression effects resulting
      from reversed parent-of-origin of the X and Y chromosomes. We found that hundreds
      of genes are differentially expressed between adult male Drosophila melanogaster
      that differ in the maternal and paternal origin of the sex chromosomes. Many of
      the differentially regulated genes are expressed specifically in testis and
      midgut cells, suggesting that sex chromosome imprinting might globally impact
      gene expression in these tissues. In contrast, we observed much fewer Y-linked
      parent-of-origin effects on genome-wide gene expression in females carrying a Y
      chromosome, indicating that gene expression in females is less sensitive to sex
      chromosome parent-of-origin. Genes whose expression differs between females
      inheriting a maternal or paternal Y chromosome also show sex chromosome parent-of
      origin effects in males, but the direction of the effects on gene expression
      (overexpression or underexpression) differ between the sexes. We suggest that
      passage of sex chromosome chromatin through male meiosis may be required for wild
      type function in F1 progeny, whereas disruption of Y-chromosome function through
      passage in the female germline likely arises because the chromosome is not
      adapted to the female germline environment. 

PMID- 24318926
TI  - The Wsc1p cell wall signaling protein controls biofilm (Mat) formation
      independently of Flo11p in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae strains of the ?1278b background generate biofilms,
      referred to as mats, on low-density agar (0.3%) plates made with rich media
      (YPD). Mat formation involves adhesion of yeast cells to the surface of the agar
      substrate and each other as the biofilm matures, resulting in elaborate water
      channels that create filigreed patterns of cells. The cell wall adhesion protein
      Flo11p is required for mat formation; however, genetic data indicate that other
      unknown effectors are also required. For example, mutations in vacuolar protein
      sorting genes that affect the multivesicular body pathway, such as vps27Delta,
      cause mat formation defects independently of Flo11p, presumably by affecting an
      unidentified signaling pathway. A cell wall signaling protein, Wsc1p, found at
      the plasma membrane is affected for localization and function by vps27Delta. We
      found that a wsc1 mutation disrupted mat formation in a Flo11p-independent
      manner. Wsc1p appears to impact mat formation through the Rom2p-Rho1p signaling
      module, by which Wsc1p also regulates the cell wall. The Bck1p, Mkk1/Mkk2, Mpk1p
      MAP kinase signaling cascade is known to regulate the cell wall downstream of
      Wsc1p-Rom2p-Rho1p but, surprisingly, these kinases do not affect mat formation.
      In contrast, Wsc1p may impact mat formation by affecting Skn7p instead. Skn7p can
      also receive signaling inputs from the Sln1p histidine kinase; however,
      mutational analysis of specific histidine kinase receiver residues in Skn7p
      indicate that Sln1p does not play an important role in mat formation, suggesting
      that Skn7p primarily acts downstream of Wsc1p to regulate mat formation.

PMID- 24318928
TI  - Improved diagnostic performance of a commercial Anaplasma antibody competitive
      enzyme-linked immunosorbent assay using recombinant major surface protein 5
      glutathione S-transferase fusion protein as antigen.
AB  - The current study tested the hypothesis that removal of maltose binding protein
      (MBP) from recombinant antigen used for plate coating would improve the
      specificity of a commercial Anaplasma antibody competitive enzyme-linked
      immunosorbent assay (cELISA). The number of 358 sera with significant MBP
      antibody binding (>=30%I) in Anaplasma-negative herds was 139 (38.8%) when tested
      using the recombinant major surface protein 5 (rMSP5)-MBP cELISA without MBP
      adsorption. All but 8 of the MBP binders were rendered negative (<30%I) using the
      commercial rMSP5-MBP cELISA with MBP adsorption, resulting in 97.8% specificity.
      This specificity was higher than some previous reports, so to improve the
      specificity of the commercial cELISA, a new recombinant antigen designated rMSP5
      glutathione S-transferase (GST) was developed, eliminating MBP from the antigen
      and obviating the need for MBP adsorption. Using the rMSP5-GST cELISA, only 1 of
      358 Anaplasma-negative sera, which included the 139 sera with significant
      (>=30%I) MBP binding in the rMSP5-MBP cELISA without MBP adsorption, was
      positive. This resulted in an improved diagnostic specificity of 99.7%. The rMSP5
      GST cELISA without MBP adsorption had comparable analytical sensitivity to the
      rMSP5-MBP cELISA with MBP adsorption and had 100% diagnostic sensitivity when
      tested with 135 positive sera defined by nested polymerase chain reaction.
      Further, the rMSP5-GST cELISA resolved 103 false-positive reactions from selected
      sera with possible false-positive reactions obtained using the rMSP5-MBP cELISA
      with MBP adsorption and improved the resolution of 29 of 31 other sera. In
      summary, the rMSP5-GST cELISA was a faster and simpler assay with higher
      specificity, comparable sensitivity, and improved resolution in comparison with
      the rMSP5-MBP cELISA with MBP adsorption. 

PMID- 24318927
TI  - Inducible defenses stay up late: temporal patterns of immune gene expression in
      Tenebrio molitor.
AB  - The course of microbial infection in insects is shaped by a two-stage process of
      immune defense. Constitutive defenses, such as engulfment and melanization, act
      immediately and are followed by inducible defenses, archetypically the production
      of antimicrobial peptides, which eliminate or suppress the remaining microbes. By
      applying RNAseq across a 7-day time course, we sought to characterize the long
      lasting immune response to bacterial challenge in the mealworm beetle Tenebrio
      molitor, a model for the biochemistry of insect immunity and persistent bacterial
      infection. By annotating a hybrid de novo assembly of RNAseq data, we were able
      to identify putative orthologs for the majority of components of the conserved
      insect immune system. Compared with Tribolium castaneum, the most closely related
      species with a reference genome sequence and a manually curated immune system
      annotation, the T. molitor immune gene count was lower, with lineage-specific
      expansions of genes encoding serine proteases and their countervailing inhibitors
      accounting for the majority of the deficit. Quantitative mapping of RNAseq reads
      to the reference assembly showed that expression of genes with predicted
      functions in cellular immunity, wound healing, melanization, and the production
      of reactive oxygen species was transiently induced immediately after immune
      challenge. In contrast, expression of genes encoding antimicrobial peptides or
      components of the Toll signaling pathway and iron sequestration response remained
      elevated for at least 7 days. Numerous genes involved in metabolism and nutrient
      storage were repressed, indicating a possible cost of immune induction.
      Strikingly, the expression of almost all antibacterial peptides followed the same
      pattern of long-lasting induction, regardless of their spectra of activity,
      signaling possible interactive roles in vivo. 

PMID- 24318929
TI  - The efficacy of plasma biomarkers in early diagnosis of Alzheimer's disease.
AB  - BACKGROUND: Early diagnosis of Alzheimer's disease (AD) is imperative for the
      prevention of disease progression and the development of effective treatments.
      OBJECTIVE: Clinically, AD diagnosis has been based on adherence to clinical
      criteria. It has recently been proposed that diagnostic criteria should also
      incorporate biomarker findings. However, the most studied candidates or group of
      candidates for AD biomarkers, including pathological processes and proteins,
      needs further research. The current study aimed to investigate the capabilities
      of the following plasma proteins in the diagnosis of AD and amnesia mild
      cognitive impairment (aMCI): peripheral interleukin (IL) 10, IL-6, amyloid-beta
      (Abeta) 40, Abeta42, phosphorylated tau 181, and total tau. METHODS: In addition
      to 122 normal control (NC) group, 97 AD patients and 54 aMCI patients were
      recruited for this study. An enzyme-linked immunosorbent assay was used to
      analyze the concentration of the following blood plasma biomarkers: IL-10, IL-6,
      Abeta40, Abeta42, phosphorylated tau 181, and total tau. RESULTS: A one-way
      analysis of variance (one-factor analysis of variance) of Abeta40 and IL-10
      levels revealed a statistically significant difference between the three groups
      (p < 0.001 and p = 0.020). Using Abeta40 >= 42.70 pg/ml as the cut-off point, the
      sensitivity of the ability of Abeta40 to discriminate between AD and NC groups
      was 80.0%, and specificity was 69.6%. CONCLUSIONS: The plasma Abeta40 biomarker
      was able to distinguish between AD and NC groups. However, the plasma biomarkers
      in the present research were not able to distinguish between aMCI and NC groups.

PMID- 24318930
TI  - Prenatal ultrasound evaluation of fetal Hb Bart's disease among pregnancies at
      risk at 11 to 14 weeks of gestation.
AB  - OBJECTIVE: The objective of this article is to evaluate the efficacy of the first
      trimester sonomarkers (11-14 weeks) in predicting hemoglobin (Hb) Bart's disease
      among fetuses at risk MATERIALS AND METHODS: Prospective analysis was conducted
      on pregnancies at risk of fetal Hb Bart's disease at 11 to 14 weeks of gestation.
      Sonographic markers including cardiothoracic (CT) ratio, peak systolic velocity
      of the middle cerebral artery (MCA-PSV), placental thickness, and nuchal
      translucency were prospectively assessed and recorded. The definite diagnosis of
      fetal Hb Bart's disease was based on DNA analysis (chorionic villus sampling) or
      subsequent fetal Hb typing (high-performance liquid chromatography;
      cordocentesis). RESULTS: Among 104 pregnancies at risk with complete sonographic
      assessment at 11 to 14 weeks of gestation, 30 fetuses were finally proven to be
      affected. The CT ratio gave the highest sensitivity, 93.3%, with specificity of
      93.2%, followed by placental thickness and MCA-PSV, respectively. Nuchal
      translucency had a very low sensitivity of 16.7%. The combination of CT ratio and
      MCA-PSV increased the sensitivity to 96.7% but somewhat compromise specificity.
      CONCLUSIONS: At 11 to 14 weeks of gestation, sonographic markers can effectively
      differentiate affected from unaffected pregnancies. The most sensitive marker was
      CT ratio plus MCA-PSV. Of couples at risk with no any sonographic markers, the
      risk of having an affected fetus is nearly eliminated.

PMID- 24318931
TI  - Addressing genetic tumor heterogeneity through computationally predictive
      combination therapy.
AB  - Recent tumor sequencing data suggest an urgent need to develop a methodology to
      directly address intratumoral heterogeneity in the design of anticancer treatment
      regimens. We use RNA interference to model heterogeneous tumors, and demonstrate
      successful validation of computational predictions for how optimized drug
      combinations can yield superior effects on these tumors both in vitro and in
      vivo. Importantly, we discover here that for many such tumors knowledge of the
      predominant subpopulation is insufficient for determining the best drug
      combination. Surprisingly, in some cases, the optimal drug combination does not
      include drugs that would treat any particular subpopulation most effectively,
      challenging straightforward intuition. We confirm examples of such a case with
      survival studies in a murine preclinical lymphoma model. Altogether, our approach
      provides new insights about design principles for combination therapy in the
      context of intratumoral diversity, data that should inform the development of
      drug regimens superior for complex tumors. SIGNIFICANCE: This study provides the
      first example of how combination drug regimens, using existing chemotherapies,
      can be rationally designed to maximize tumor cell death, while minimizing the
      outgrowth of clonal subpopulations.

PMID- 24318932
TI  - Osteopontin, inflammation and myogenesis: influencing regeneration, fibrosis and
      size of skeletal muscle.
AB  - Osteopontin is a multifunctional matricellular protein that is expressed by many
      cell types. Through cell-matrix and cell-cell interactions the molecule elicits a
      number of responses from a broad range of target cells via its interaction with
      integrins and the hyaluronan receptor CD44. In many tissues osteopontin has been
      found to be involved in important physiological and pathological processes,
      including tissue repair, inflammation and fibrosis. Post-natal skeletal muscle is
      a highly differentiated and specialised tissue that retains a remarkable capacity
      for regeneration following injury. Regeneration of skeletal muscle requires the
      co-ordinated activity of inflammatory cells that infiltrate injured muscle and
      are responsible for initiating muscle fibre degeneration and phagocytosis of
      necrotic tissue, and muscle precursor cells that regenerate the injured muscle
      fibres. This review focuses on the current evidence that osteopontin plays
      multiple roles in skeletal muscle, with particular emphasis on its role in
      regeneration and fibrosis following injury, and in determining the severity of
      myopathic diseases such as Duchenne muscular dystrophy. 

PMID- 24318933
TI  - Mesenchymal cells emerge as primary contributors to fibrosis in multiple tissues.
AB  - A longstanding controversy exists regarding the cellular origin of myofibroblasts
      in tissue fibrosis. A recent study by Hung and colleagues (Am J Respir Crit Care
      Med 188(7):820-830, 2013) used genetic fate mapping of FoxD1 embryonic progenitor
      cells to show a major and direct contribution of mesenchymal cells to
      fibrogenesis in the lung. Future studies using FoxD1-specific inducible knockout
      models of pro-fibrotic genes such as CCN2 will be valuable for determining anti
      fibrotic drug targets. The emergence of pericyte-like myofibroblast precursors
      also raises the question of whether mesenchymal stem cells in various niches
      contribute to fibrotic responses throughout the body. 

PMID- 24318934
TI  - Effects of a novel MC4R agonist on maintenance of reduced body weight in diet
      induced obese mice.
AB  - OBJECTIVE: The physiology of the weight-reduced (WR) state suggests that
      pharmacologic agents affecting energy homeostasis may have greater efficacy in WR
      individuals. Our aim was to establish a protocol that allows for evaluation of
      efficacy of weight maintenance agents and to assess the effectiveness of AZD2820,
      a novel melanocortin 4 receptor (MC4R) agonist in such a paradigm. METHODS: MC4R
      agonist was administered in stratified doses to mice who were either fed high-fat
      diet ad libitum (AL) throughout the study; or stabilized at a 20% reduced body
      weight (BW), administered the drug for 4 weeks, and thereafter released from
      caloric restriction while continuing to receive the drug (WR). RESULTS: After
      release of WR mice to AL feeding, the high-dose group (53.4 nmol/day) regained
      12.4% less BW than their vehicle-treated controls since the beginning of drug
      treatment. In WR mice, 10.8 nmol/day of the agonist was sufficient to maintain
      these animals at 95.1% of initial BW versus 53.4 nmol/day required to maintain
      the BW of AL animals (94.5%). CONCLUSIONS: In the WR state, the MC4R agonist was
      comparably efficacious to a five-fold higher dose in the AL state. This protocol
      provides a model for evaluating the mechanisms and quantitative efficacy of
      weight-maintenance strategies and agents.

PMID- 24318935
TI  - Violence among people with schizophrenia: phenotypes and neurobiology.
AB  - People with schizophrenia are at increased risk, as compared to the general
      population, to acquire convictions for violent crimes and homicide. They also
      show elevated levels of aggressive behaviour. While psychotic symptoms explain
      aggressive behaviour that is common during acute episodes, they do not explain
      such behaviour at other stages of illness or prior to illness onset. Three
      distinct phenotypes have been identified: individuals with a childhood onset of
      conduct disorder who display antisocial and aggressive behaviour both before and
      after schizophrenia onset; individuals with no history of conduct problems who
      begin engaging in aggressive behaviour as illness onsets; and individuals who
      after many years of illness engage in a severe physical assault. Little is known
      about the aetiology of the three types of offenders and about the neural
      mechanisms that initiate and maintain these behaviours. We hypothesize that
      schizophrenia preceded by conduct disorder is associated with a combination of
      genes conferring vulnerability for both disorders and altering the effects of
      environmental factors on the brain, and thereby, with a distinct pattern of
      neural development. Some evidence is available to support this hypothesis. By
      contrast, offending among adults with schizophrenia who have no history of such
      behaviour prior to illness may result from the changes in the brain that occur as
      illness onsets, and that are further altered by comorbid conditions such as
      substance misuse, or by the progressive changes in the brain through adulthood
      that may result from the illness and from the use of antipsychotic medications. 

PMID- 24318937
TI  - Body composition and cardiometabolic disease risk factors in captive baboons
      (Papio hamadryas sp.): sexual dimorphism.
AB  - Baboons (Papio hamadryas sp.) exhibit significant sexual dimorphism in body size.
      Sexual dimorphism is also exhibited in a number of circulating factors associated
      with risk of cardiometabolic disease. We investigated whether sexual dimorphism
      in body size and composition underlie these differences. We examined data from 28
      male and 24 female outdoor group-housed young adult baboons enrolled in a
      longitudinal observational study of cardiometabolic disease risk factors. Animals
      were sedated with ketamine HCl (10 mg/kg) before undergoing venous blood draws,
      basic body measurements, and dual-energy X-ray absorptiometry body composition
      scans. Percentage glycated hemoglobin A1c (%HbA1c ) was measured in whole blood.
      Serum samples were analyzed for glucose, insulin, C-peptide, high-density
      lipoprotein, and triglyceride concentrations. Males were heavier and had greater
      body length and lean tissue mass than females. Females had a greater body fat
      percentage relative to males (10.8 +/- 6.4 vs. 6.9 +/- 4.0, P = 0.01). Although C
      peptide, fasting glucose, and %HbA1c did not differ between the sexes, females
      had greater fasting insulin and triglyceride compared to their male counterparts.
      Insulin and percentage body fat were significantly correlated in males (r = 0.61,
      P = 0.001) and to a lesser extent in females (r = 0.43, P = 0.04). Overall,
      relations between adiposity and fasting insulin and fasting triglyceride were
      stronger in males. After accounting for differences in percentage body fat,
      fasting insulin and triglyceride were no longer statistically different between
      males and females. Despite stronger correlations between relative adiposity and
      insulin and triglyceride in males, the higher fasting insulin and triglyceride of
      female baboons may be underlain by their greater relative body fat masses.

PMID- 24318938
TI  - Body size and premolar evolution in the early-middle eocene euprimates of
      Wyoming.
AB  - The earliest euprimates to arrive in North America were larger-bodied notharctids
      and smaller-bodied omomyids. Through the Eocene, notharctids generally continued
      to increase in body size, whereas omomyids generally radiated within small- and
      increasingly mid-sized niches in the middle Eocene. This study examines the
      influence of changing body size and diet on the evolution of the lower fourth
      premolar in Eocene euprimates. The P4 displays considerable morphological
      variability in these taxa. Despite the fact that most studies of primate dental
      morphology have focused on the molars, P4 can also provide important
      paleoecological insights. We analyzed the P4 from 177 euprimate specimens,
      representing 35 species (11 notharctids and 24 omomyids), in three time bins of
      approximately equal duration: early Wasatchian, late Wasatchian, and Bridgerian.
      Two-dimensional surface landmarks were collected from lingual photographs,
      capturing important variation in cusp position and tooth shape. Disparity metrics
      were calculated and compared for the three time bins. In the early Eocene,
      notharctids have a more molarized P4 than omomyids. During the Bridgerian,
      expanding body size range of omomyids was accompanied by a significant increase
      in P4 disparity and convergent evolution of the semimolariform condition in the
      largest omomyines. P4 morphology relates to diet in early euprimates, although
      patterns vary between families.

PMID- 24318939
TI  - Dental topography of platyrrhines and prosimians: convergence and contrasts.
AB  - Dental topographic analysis is the quantitative assessment of shape of three
      dimensional models of tooth crowns and component features. Molar topographic
      curvature, relief, and complexity correlate with aspects of feeding behavior in
      certain living primates, and have been employed to investigate dietary ecology in
      extant and extinct primate species. This study investigates whether dental
      topography correlates with diet among a diverse sample of living platyrrhines,
      and compares platyrrhine topography with that of prosimians. We sampled 111 lower
      second molars of 11 platyrrhine genera and 121 of 20 prosimian genera. For each
      tooth we calculated Dirichlet normal energy (DNE), relief index (RFI), and
      orientation patch count (OPCR), quantifying surface curvature, relief, and
      complexity respectively. Shearing ratios and quotients were also measured.
      Statistical analyses partitioned effects of diet and taxon on topography in
      platyrrhines alone and relative to prosimians. Discriminant function analyses
      assessed predictive diet models. Results indicate that platyrrhine dental
      topography correlates to dietary preference, and platyrrhine-only predictive
      models yield high rates of accuracy. The same is true for prosimians. Topographic
      variance is broadly similar among platyrrhines and prosimians. One exception is
      that platyrrhines display higher average relief and lower relief variance,
      possibly related to lower relative molar size and functional links between relief
      and tooth longevity distinct from curvature or complexity. Explicitly
      incorporating phylogenetic distance matrices into statistical analyses of the
      combined platyrrhine-prosimian sample results in loss of significance of dietary
      effects for OPCR and SQ, while greatly increasing dietary significance of RFI.

PMID- 24318940
TI  - Growth and fluctuating asymmetry of human newborns: influence of inbreeding and
      parental education.
AB  - Historically, medical concerns about the deleterious effects of closely inbred
      marriages have focused on the risk posed by recessive Mendelian disease, with
      much less attention to developmental instability. We studied the effects of
      inbreeding (first-cousin marriage) on growth and fluctuating asymmetry of 200
      full-term infants (101 inbred and 99 outbred) whose parents were of similar
      socioeconomic status in Sivas Province, Turkey. In addition to differences in
      their mean inbreeding coefficients (f = 1/16 for first cousins and f < 1/1,024
      for unrelated parents), the consanguineous parents were less well educated (3
      years, on average for both husbands and wives). We measured weight, height, head
      circumference, and chest circumference of the newborns, as well as four bilateral
      traits (ear width, ear length, and second and fourth digit lengths). After taking
      education into account, none of the measures of size (weight, height, head
      circumference, and chest circumference) and fluctuating asymmetry differed
      between the inbred and outbred groups. Male children of well-educated parents,
      however, were larger and had less fluctuating asymmetry. Female children of well
      educated parents weighed more than those of less well-educated parents, but were
      otherwise indistinguishable for height, head circumference, chest circumference,
      and fluctuating asymmetry. We conclude that inbreeding depression causes neither
      an increase in fluctuating asymmetry of full-term newborns, nor a decrease in
      body size. Unmeasured variables correlated with education appear to have an
      effect on fluctuating asymmetry and size of male children and only a weak effect
      on size (weight) of female children.

PMID- 24318936
TI  - Neurogenetics of aggressive behavior: studies in rodents.
AB  - Aggressive behavior is observed in many animal species, such as insects, fish,
      lizards, frogs, and most mammals including humans. This wide range of
      conservation underscores the importance of aggressive behavior in the animals'
      survival and fitness, and the likely heritability of this behavior. Although
      typical patterns of aggressive behavior differ between species, there are several
      concordances in the neurobiology of aggression among rodents, primates, and
      humans. Studies with rodent models may eventually help us to understand the
      neurogenetic architecture of aggression in humans. However, it is important to
      recognize the difference between the ecological and ethological significance of
      aggressive behavior (species-typical aggression) and maladaptive violence
      (escalated aggression) when applying the findings of aggression research using
      animal models to human or veterinary medicine. Well-studied rodent models for
      aggressive behavior in the laboratory setting include the mouse (Mus musculus),
      rat (Rattus norvegicus), hamster (Mesocricetus auratus), and prairie vole
      (Microtus ochrogaster). The neural circuits of rodent aggression have been
      gradually elucidated by several techniques, e.g., immunohistochemistry of
      immediate-early gene (c-Fos) expression, intracranial drug microinjection, in
      vivo microdialysis, and optogenetics techniques. Also, evidence accumulated from
      the analysis of gene-knockout mice shows the involvement of several genes in
      aggression. Here, we review the brain circuits that have been implicated in
      aggression, such as the hypothalamus, prefrontal cortex (PFC), dorsal raphe
      nucleus (DRN), nucleus accumbens (NAc), and olfactory system. We then discuss the
      roles of glutamate and gamma-aminobutyric acid (GABA), excitatory and inhibitory
      amino acids in the brain, as well as their receptors, in controlling aggressive
      behavior, focusing mainly on recent findings. At the end of this chapter, we
      discuss how genes can be identified that underlie individual differences in
      aggression, using the so-called forward genetics approach. 

PMID- 24318941
TI  - Ontogenetic scaling of the human nose in a longitudinal sample: implications for
      genus Homo facial evolution.
AB  - Researchers have hypothesized that nasal morphology, both in archaic Homo and in
      recent humans, is influenced by body mass and associated oxygen consumption
      demands required for tissue maintenance. Similarly, recent studies of the adult
      human nasal region have documented key differences in nasal form between males
      and females that are potentially linked to sexual dimorphism in body size,
      composition, and energetics. To better understand this potential developmental
      and functional dynamic, we first assessed sexual dimorphism in the nasal cavity
      in recent humans to determine when during ontogeny male-female differences in
      nasal cavity size appear. Next, we assessed whether there are significant
      differences in nasal/body size scaling relationships in males and females during
      ontogeny. Using a mixed longitudinal sample we collected cephalometric and
      anthropometric measurements from n = 20 males and n = 18 females from 3.0 to
      20.0+ years of age totaling n = 290 observations. We found that males and females
      exhibit similar nasal size values early in ontogeny and that sexual dimorphism in
      nasal size appears during adolescence. Moreover, when scaled to body size, males
      exhibit greater positive allometry in nasal size compared to females. This
      differs from patterns of sexual dimorphism in overall facial size, which are
      already present in our earliest age groups. Sexually dimorphic differences in
      nasal development and scaling mirror patterns of ontogenetic variation in
      variables associated with oxygen consumption and tissue maintenance. This
      underscores the importance of considering broader systemic factors in
      craniofacial development and may have important implications for the study of
      patters craniofacial evolution in the genus Homo.

PMID- 24318942
TI  - Manual lateralization in wild redfronted lemurs (Eulemur rufifrons) during
      spontaneous actions and in an experimental task.
AB  - The dominant use of one hand is a striking feature of humans, but manual
      lateralization can be found in a variety of other species as well. In primates,
      the lateralization in hand use varies among species and several theories such as
      the "postural origin," "task complexity," or "development theory" have been
      suggested to explain this variation. In order to contribute comparative data on
      this phenomenon from a basal primate, we studied manual lateralization in wild
      redfronted lemurs (Eulemur rufifrons). Data were collected on four groups at
      Kirindy Forest, western Madagascar, during spontaneous actions and by confronting
      them with artificial feeding boxes. The lemurs did not exhibit manual
      lateralization on a group level in either condition. More individuals showed a
      hand preference in the experimental task, and the preferences were stronger
      compared to spontaneous actions. The direction of individual hand preferences was
      not consistent across the two conditions. The results of this study show that
      measuring manual laterality in different contexts can yield different results.
      Manual lateralization in wild redfronted lemurs therefore seems to be flexible
      and situation dependent and probably not ecologically relevant in their natural
      habitat.

PMID- 24318943
TI  - Daily activity and light exposure levels for five species of lemurs at the Duke
      Lemur Center.
AB  - Light is the primary synchronizer of all biological rhythms, yet little is known
      about the role of the 24-hour luminous environment on nonhuman primate circadian
      patterns, making it difficult to understand the photic niche of the ancestral
      primate. Here we present the first data on proximate light-dark exposure and
      activity-rest patterns in free-ranging nonhuman primates. Four individuals each
      of five species of lemurs at the Duke Lemur Center (Eulemur mongoz, Lemur catta,
      Propithecus coquereli, Varecia rubra, and Varecia variegata variegata) were
      fitted with a Daysimeter-D pendant that contained light and accelerometer
      sensors. Our results reveal common as well as species-specific light exposure and
      behavior patterns. As expected, all five species were more active between sunrise
      and sunset. All five species demonstrated an anticipatory increase in their pre
      sunrise activity that peaked at sunrise with all but V. rubra showing a reduction
      within an hour. All five species reduced activity during mid-day. Four of the
      five stayed active after sunset, but P. coquereli began reducing their activity
      about 2 hours before sunset. Other subtle differences in the recorded light
      exposure and activity patterns suggest species-specific photic niches and
      behaviors. The eventual application of the Daysimeter-D in the wild may help to
      better understand the adaptive evolution of ancestral primates.

PMID- 24318944
TI  - Nutritional correlates of the "lean season": effects of seasonality and frugivory
      on the nutritional ecology of diademed sifakas.
AB  - Primate field studies often identify "lean seasons," when preferred foods are
      scarce, and lower-quality, abundant foods (fallback foods) are consumed. Here, we
      quantify the nutritional implications of these terms for two diademed sifaka
      groups (Propithecus diadema) in Madagascar, using detailed feeding observations
      and chemical analyses of foods. In particular, we sought to understand 1) how
      macronutrient and energy intakes vary seasonally, including whether these intakes
      respond in similar or divergent ways; 2) how the amount of food ingested varies
      seasonally (including whether changes in amount eaten may compensate for altered
      food quality); and 3) correlations between these variables and the degree of
      frugivory. In the lean season, sifakas shifted to non-fruit foods (leaves and
      flowers), which tended to be high in protein while low in other macronutrients
      and energy, but the average composition of the most used foods in each season was
      similar. They also showed dramatic decreases in feeding time, food ingested, and
      consequently, daily intake of macronutrients and energy. The degree of frugivory
      in the daily diet was a strong positive predictor of feeding time, amount
      ingested and all macronutrient and energy intakes, though season had an
      independent effect. These results suggest that factors restricting how much food
      can be eaten (e.g., handling time, availability, or intrinsic characteristics
      like fiber and plant secondary metabolites) can be more important than the
      nutritional composition of foods themselves in determining nutritional outcomes-a
      finding with relevance for understanding seasonal changes in behavior, life
      history strategies, competitive regimes, and conservation planning.

PMID- 24318945
TI  - The consequences of linear growth stunting: influence on body composition among
      youth in the Bolivian Amazon.
AB  - Stunting, or linear growth retardation, has been documented in up to half of all
      children in rural indigenous populations of South America. Stunting is well
      understood as a signal of adverse conditions during growth, and has been
      associated with developmentally induced modifications to body composition,
      including body fat and muscularity, that stem from early growth restriction. This
      article examines the relation between short stature and three anthropometric
      indicators of body composition during childhood and adolescence among a rural,
      indigenous population of forager-horticulturalists. Anthropometric data were
      collected annually from 483 Tsimane' youth, ages 2-10 years, in 13 communities in
      the Beni region of Bolivia for 6 consecutive years (2002-2007). Baseline height
      for-age was used to indicate stunting (HAZ < -2.0) and compared with z-scores of
      body mass index (BMI), sum of two skinfolds, and arm muscle area. Multilevel
      regression models indicate baseline stunting is associated with lower BMI z
      scores (B = -0.386; P < 0.001), body fatness (ZSkinfold, B = -0.164; P < 0.001),
      and arm muscularity (AMAZ, B = -0.580; P < 0.001) in youth across a period of 6
      years. When split by sex, there was a stronger relation between baseline stunting
      and lower skinfold body fat scores among girls (B = -0.244; P < 0.001) than boys
      (B = -0.080; P = 0.087). In contrast, baseline stunting was associated with lower
      arm muscularity in both girls (B = -0.498; P < 0.001) and boys (B = -0.646; P <
      0.001). The relation between linear growth restriction and indicators of body
      composition persist into adolescence, providing additional insight into the
      influence of adverse conditions during growth.

PMID- 24318946
TI  - The prevalence of pulp stones in historical populations from the middle Euphrates
      valley (Syria).
AB  - There are many reports in the literature concerning pulp stones in contemporary
      living populations, but there are no descriptions of cases of pulp stones and
      their prevalence in populations of the past. Here we present a study of pulp
      stones in a series of archaeologically derived samples from the Middle Euphrates
      Valley (Syria) obtained from two sites: Terqa and Tell Masaikh. The specimens
      were assigned to five periods: Early Bronze (2650-2350 BC); Middle Bronze (2200
      1700 BC); late Roman (AD 200-400); Islamic (AD 600-1200); and Modern Islamic (AD
      1850-1950). A total of 529 teeth representing 117 adult individuals of both sexes
      were examined. Pulp stones were identified by X-ray and 10 selected specimens
      were sectioned for histological study. Pulp stones were found in 99 of 117
      individuals (85%) and in 271 of 529 (51%) teeth. Pulp stone prevalence was found
      to increase with age, for individuals of older age classes have more pulp stones
      than younger individuals. Intriguingly, the prevalence of single pulp stones was
      higher among older individuals (36-45, >46), while younger individuals (17-25, 26
      35) more often possessed multiple stones. Individuals with moderate to highly
      advanced dental wear have pulp stones significantly more often than individuals
      whose tooth wear is limited to invisible or very small facets. Though there is no
      statistical significance in the prevalence of pulp stones across chronological
      periods, it appears that a high level of calcium in the diet is accompanied by a
      greater prevalence of pulp stones.

PMID- 24318947
TI  - Brief communication: timing of spheno-occipital closure in modern Western
      Australians.
AB  - The spheno-occipital synchondrosis is a craniofacial growth centre between the
      occipital and sphenoid bones-its ossification persists into adolescence, which
      for the skeletal biologist, means it has potential application for estimating
      subadult age. Based on previous research the timing of spheno-occipital fusion is
      widely variable between and within populations, with reports of complete fusion
      in individuals as young as 11 years of age and nonfusion in adults. The aim of
      this study is, therefore, to examine this structure in a mixed sex sample of
      Western Australian individuals that developmentally span late childhood to
      adulthood. The objective is to develop statistically quantified age estimation
      standards based on scoring the degree of spheno-occipital fusion. The sample
      comprises multidetector computed tomography (MDCT) scans of 312 individuals (169
      male; 143 female) between 5 and 25 years of age. Each MDCT scan is visualized in
      a standardized sagittal plane using three-dimensional oblique multiplanar
      reformatting. Fusion status is scored according to a four-stage system.
      Transition analysis is used to calculate age ranges for each defined stage and
      determine the mean age for transition between an unfused, fusing and fused
      status. The maximum likelihood estimates for the transition from open to fusing
      in the endocranial half is 14.44 years (male) and 11.42 years (female);
      transition from fusion in the ectocranial half to complete fusion is 16.16 years
      (male) and 13.62 years (female). This study affirms the potential value of
      assessing the degree of fusion in the spheno-occipital synchondrosis as an
      indicator of skeletal age.

PMID- 24318948
TI  - Brief communication: Orphaned Male Chimpanzees die young even after weaning.
AB  - If a social-living animal has a long life span, permitting different generations
      to co-exist within a social group, as is the case in many primate species, it can
      be beneficial for a parent to continue to support its weaned offspring to
      increase the latter's survival and/or reproductive success. Chimpanzees have an
      even longer period of dependence on their mothers' milk than do humans, and
      consequently, offspring younger than 4.5-5 years old cannot survive if the mother
      dies. Most direct maternal investments, such as maternal transportation of
      infants and sharing of night shelters (beds or nests), end with nutritional
      weaning. Thus, it had been assumed that a mother's death was no longer critical
      to the survival of weaned offspring, in contrast to human children, who continue
      to depend on parental care long after weaning. However, in theory at least,
      maternal investment in a chimpanzee son after weaning could be beneficial because
      in chimpanzees' male-philopatric society, mother and son co-exist for a long time
      after the offspring's weaning. Using long-term demographic data for a wild
      chimpanzee population in the Mahale Mountains, Tanzania, we show the first
      empirical evidence that orphaned chimpanzee sons die younger than expected even
      if they lose their mothers after weaning. This suggests that long-lasting, but
      indirect, maternal investment in sons continues several years after weaning and
      is vital to the survival of the sons. The maternal influence on males in the male
      philopatric societies of hominids may be greater than previously believed.

PMID- 24318949
TI  - Brief communication: a proposed method for the assessment of pubertal stage in
      human skeletal remains using cervical vertebrae maturation.
AB  - The assessment of age-at-death in non-adult skeletal remains is under constant
      review. However, in many past societies an individual's physical maturation may
      have been more important in social terms than their exact age, particularly
      during the period of adolescence. In a recent article (Shapland and Lewis: Am J
      Phys Anthropol 151 (2013) 302-310) highlighted a set of dental and skeletal
      indicators that may be useful in mapping the progress of the pubertal growth
      spurt. This article presents a further skeletal indicator of adolescent
      development commonly used by modern clinicians: cervical vertebrae maturation
      (CVM). This method is applied to a collection of 594 adolescents from the
      medieval cemetery of St. Mary Spital, London. Analysis reveals a potential delay
      in ages of attainment of the later CVM stages compared with modern adolescents,
      presumably reflecting negative environmental conditions for growth and
      development. The data gathered on CVM is compared to other skeletal indicators of
      pubertal maturity and long bone growth from this site to ascertain the usefulness
      of this method on archaeological collections.

PMID- 24318950
TI  - Technical note: virtual reconstruction of KNM-ER 1813 Homo habilis cranium.
AB  - A very limiting factor for paleoanthropological studies is the poor state of
      preservation of the human fossil record, where fragmentation and deformation are
      considered normal. Although anatomical information can still be gathered from a
      distorted fossil, such specimens must typically be excluded from advanced
      morphological and morphometric analyses, thus reducing the fossil sample size
      and, ultimately, our knowledge of human evolution. In this contribution we
      provide the first digital reconstruction of the KNM-ER 1813 Homo habilis cranium.
      Based on state of-the-art three-dimensional digital modeling and geometric
      morphometric (GM) methods, the facial portion was aligned to the neurocranium,
      the overall distortion was removed, and the missing regions were restored. The
      reconstructed KNM-ER 1813 allows for an adjustment of the anthropometric
      measurements gathered on the original fossil. It is suitable for further
      quantitative studies, such as GM analyses focused on skull morphology or for
      finite element analysis to explore the mechanics of early Homo feeding behavior
      and diet.

PMID- 24318951
TI  - Reply: "questioning the use of privately owned apes in anthropological research".

PMID- 24318952
TI  - Therapy for latent HIV-1 infection: the role of histone deacetylase inhibitors.
AB  - Persistence of HIV-1 in latently infected CD4(+) T-cells prevents eradication in
      HIV-infected treated patients. Latency is characterized by a reversible silencing
      of transcription of integrated HIV-1. Several molecular mechanisms have been
      described which contribute to latency, including the establishment and
      maintenance of repressive chromatin on the HIV-1 promoter. Histone deacetylation
      is a landmark modification associated with transcriptional repression of the HIV
      1 promoter and inhibition of histone deacetylase enzymes (HDACs) reactivates
      latent HIV-1. Here, we review the different HDAC inhibitors that have been
      studied in HIV-1 latency and their therapeutic potential in reactivating latent
      HIV-1. 

PMID- 24318953
TI  - Factors associated with response, survival, and limb salvage in patients
      undergoing isolated limb infusion.
AB  - BACKGROUND: Isolated limb infusion (ILI) is a percutaneous method of delivering
      regional chemotherapy to patients with recurrent tumors of the extremity. This
      study determines predictors of response, survival, and limb salvage. METHODS:
      Single institution data from a prospective clinical trial and subsequent ILI
      experience were reviewed. Limb tumor burden was assessed in melanoma patients
      with "high" (>=10 lesions or one lesion >3 cm) or "low" burden (<10 lesions and
      no lesion >3 cm). Response was assessed at 3 months from ILI. RESULTS: Between
      1999 and 2011, 62 patients underwent ILI (58 melanoma, 2 Merkel cell carcinoma
      (MCC), 2 soft tissue sarcoma (STS)). Low tumor burden patients had more complete
      responses (CR) (11/23, 48%) than high tumor burden (3/32, 9%, P < 0.001); they
      had higher 5-year survival (69% vs. 29%, P = .007). Five-year survival rates
      based on response: 91% CR, 53% partial response (PR), 25% less than PR (P =
      0.042, CR vs. PR). 7 patients (11%) underwent amputation due to disease
      progression; 3 had prior CR or PR. CONCLUSIONS: Low tumor burden is a significant
      predictor of response in melanoma patients. Response to ILI is a significant
      predictor of survival. Progression of limb disease requiring amputation is not
      associated with any factors.

PMID- 24318954
TI  - Characterization of a highly flexible self-assembling protein system designed to
      form nanocages.
AB  - The design of proteins that self-assemble into well-defined, higher order
      structures is an important goal that has potential applications in synthetic
      biology, materials science, and medicine. We previously designed a two-component
      protein system, designated A-(+) and A-(-), in which self-assembly is mediated by
      complementary electrostatic interactions between two coiled-coil sequences
      appended to the C-terminus of a homotrimeric enzyme with C3 symmetry. The coiled
      coil sequences are attached through a short, flexible spacer sequence providing
      the system with a high degree of conformational flexibility. Thus, the primary
      constraint guiding which structures the system may assemble into is the symmetry
      of the protein building block. We have now characterized the properties of the
      self-assembling system as a whole using native gel electrophoresis and analytical
      ultracentrifugation (AUC) and the properties of individual assemblies using cryo
      electron microscopy (EM). We show that upon mixing, A-(+) and A-(-) form only six
      different complexes in significant concentrations. The three predominant
      complexes have hydrodynamic properties consistent with the formation of
      heterodimeric, tetrahedral, and octahedral protein cages. Cryo-EM of size
      fractionated material shows that A-(+) and A-(-) form spherical particles with
      diameters appropriate for tetrahedral or octahedral protein cages. The particles
      varied in diameter in an almost continuous manner suggesting that their
      structures are extremely flexible. 

PMID- 24318955
TI  - Management of herbicide resistance in wheat cropping systems: learning from the
      Australian experience.
AB  - Herbicide resistance continues to escalate in weed populations infesting global
      wheat (Triticum aestivum L.) crops, threatening grain production and thereby food
      supply. Conservation wheat production systems are reliant on the use of efficient
      herbicides providing low-cost, selective weed control in intensive cropping
      systems. The resistance-driven loss of herbicide resources combined with limited
      potential for new herbicide molecules means greater emphasis must be placed on
      preserving existing herbicides. For more than two decades, since the initial
      recognition of the dramatic consequences of herbicide resistance, the challenge
      of introducing additional weed control strategies into herbicide-based weed
      management programmes has been formidable. Throughout this period, herbicide
      resistance has expanded unabated across the world's wheat production regions.
      However, in Australia, where herbicide resources have become desperately
      depleted, the adoption of harvest weed seed control is evidence, at last, of a
      successful approach to sustainable weed management in wheat production systems.
      Growers routinely including strategies to target weed seeds during crop harvest,
      as part of herbicide-based weed management programmes, are now realising
      significant weed control and crop production benefits. When combined with an
      attitude of zero weed tolerance, there is evidence of a sustainable weed control
      future for wheat production systems. The hard-learned lessons of Australian
      growers can now be viewed by global wheat producers as an example of how to stop
      the continual loss of herbicide resources in productive cropping systems.

PMID- 24318956
TI  - Is digoxin use for cardiovascular disease associated with risk of prostate
      cancer?
AB  - PURPOSE: Digoxin is a commonly used medication for heart failure and cardiac
      arrhythmias that has recently been suggested as a novel chemotherapeutic agent.
      Preclinical studies of prostate cancer (PCa) have shown anti-tumor activity with
      digoxin. We explore the relationship between use of digoxin and PCa risk.
      METHODS: Data from a population-based case-control study of incident cases aged
      35-74 years at PCa diagnosis in 2002-2005 in King County, Washington were
      available. Controls were identified by random digit dialing and frequency matched
      by age. Use of digoxin was determined from in-person questionnaires regarding
      medical and prescription history. The relationship of digoxin use with PCa risk
      was evaluated with logistic regression. RESULTS: One thousand one cases of PCa
      and 942 controls were analyzed. The prevalence of digoxin use in controls was
      2.7%, and use was positively correlated with age. In multivariate analysis
      adjusting for age, race, PSA screening, and family history of PCa, digoxin use
      was associated with a reduction in the odds ratio of PCa (OR 0.58, 95% CI: 0.30
      1.10). Among those with >=3 PSA tests over the preceding 5 years (546 cases, 380
      controls), digoxin use was associated with a stronger reduction of PCa risk (OR
      0.44, 95% CI: 0.20-0.98). CONCLUSION: These data indicate digoxin use may be
      associated with a reduction in risk of PCa. Given the potential mechanisms by
      which digoxin may exert an anti-neoplastic effect and other recent studies
      showing a negative association between digoxin use and PCa, further research is
      warranted.

PMID- 24318957
TI  - Sustainability of winter tourism in a changing climate over Kashmir Himalaya.
AB  - Mountain areas are sensitive to climate change. Implications of climate change
      can be seen in less snow, receding glaciers, increasing temperatures, and
      decreasing precipitation. Climate change is also a severe threat to snow-related
      winter sports such as skiing, snowboarding, and cross-country skiing. The change
      in climate will put further pressure on the sensitive environment of high
      mountains. Therefore, in this study, an attempt has been made to know the impact
      of climate change on the snow precipitation, water resources, and winter tourism
      in the two famous tourist resorts of the Kashmir Valley. Our findings show that
      winters are getting prolonged with little snow falls on account of climate
      change. The average minimum and maximum temperatures are showing statistically
      significant increasing trends for winter months. The precipitation is showing
      decreasing trends in both the regions. A considerable area in these regions
      remains under the snow and glacier cover throughout the year especially during
      the winter and spring seasons. However, time series analysis of LandSat MODIS
      images using Normalized Difference Snow Index shows a decreasing trend in snow
      cover in both the regions from past few years. Similarly, the stream discharge,
      comprising predominantly of snow- and glacier-melt, is showing a statistically
      significant declining trend despite the melting of these glaciers. The predicted
      futuristic trends of temperature from Predicting Regional Climates for Impact
      Studies regional climate model are showing an increase which may enhance snow
      melting in the near future posing a serious threat to the sustainability of
      winter tourism in the region. Hence, it becomes essential to monitor the changes
      in temperature and snow cover depletion in these basins in order to evaluate
      their effect on the winter tourism and water resources in the region. 

PMID- 24318958
TI  - A collimated detection system for assessing leakage dose from medical linear
      accelerators at the patient plane.
AB  - Leakage radiation from linear accelerators can make a significant contribution to
      healthy tissue dose in patients undergoing radiotherapy. In this work
      thermoluminescent dosimeters (LiF:Mg,Cu,P TLD chips) were used in a focused lead
      cone loaded with TLD chips for the purpose of evaluating leakage dose at the
      patient plane. By placing the TLDs at one end of a stereotactic cone, a focused
      measurement device is created; this was tested both in and out of the primary
      beam of a Varian 21-iX linac using 6 MV photons. Acrylic build up material of 1.2
      cm thickness was used inside the cone and measurements made with either one or
      three TLD chips at a given distance from the target. Comparing the readings of
      three dosimeters in one plane inside the cone offered information regarding the
      orientation of the cone relative to a radiation source. Measurements in the
      patient plane with the linac gantry at various angles demonstrated that leakage
      dose was approximately 0.01% of the primary beam out of field when the cone was
      pointed directly towards the target and 0.0025% elsewhere (due to scatter within
      the gantry). No specific 'hot spots' (e.g., insufficient shielding or gaps at
      abutments) were observed. Focused cone measurements facilitate leakage dose
      measurements from the linac head directly at the patient plane and allow one to
      infer the fraction of leakage due to 'direct' photons (along the ray-path from
      the bremsstrahlung target) and that due to scattered photons.

PMID- 24318959
TI  - Interventions to reduce the number of falls among older adults with/without
      cognitive impairment: an exploratory meta-analysis.
AB  - OBJECTIVE: This exploratory meta-analysis aimed to examine and compare the
      effective interventions to prevent falls among institutionalized/non
      institutionalized older adults without cognitive impairment with interventions to
      prevent falls for older adults with cognitive impairment. DESIGN: A database
      search identified 111 trials published between January 1992 and August 2012 that
      evaluated fall-prevention interventions among institutionalized/non
      institutionalized older adults with and without cognitive impairment as measured
      by valid cognition scales. RESULTS: Exercise alone intervention was similar
      effective on reducing the numbers of falls among older adults without cognitive
      impairment regardless of setting (non-institutionalized: OR = 0.783, 95%
      confidence interval (CI) = 0.656-0.936; p = 0.007 institutionalized: OR = 0.799,
      95% CI = 0.646-0.988, p = 0.038). Vitamin D/calcium supplementation had a
      positive effect on the reduction of numbers of falls among non-institutionalized
      older adults without cognitive impairment (OR = 0.789, 95% CI = 0.631-0.985, p =
      0.036), as did home visits and environment modification (OR = 0.751, 95% CI =
      0.565-0.998, p = 0.048). Exercise alone, exercise-related multiple interventions,
      and multifactorial interventions were associated with positive outcomes among
      both institutionalized and non-institutionalized older adults with cognitive
      impairment, but studies are limited. CONCLUSIONS: Single exercise interventions
      can significantly reduce numbers of falls among older adults with and without
      cognitive impairment in institutional or non-institutional settings. Vitamin D
      and calcium supplementation, home visits, and environment modification can reduce
      the risk of falls among older adults in non-institutional settings. Exercise
      related multiple interventions and multifactorial interventions may only be
      effective for preventing falls in older adults with cognitive impairment.

PMID- 24318961
TI  - Form factor dispersion at La M5,4 edges and average density of resonant atoms.
AB  - Resonant soft x-ray scattering on complex oxide superlattices shows very large
      variations in the superlattice reflection position and intensity near La M5,4
      edges. Resonant dispersion of the La x-ray form factor describes the observations
      well. We determine the average density of resonant La atoms and the thickness of
      superlattice layers. 

PMID- 24318960
TI  - Engineering hydrogen gas production from formate in a hyperthermophile by
      heterologous production of an 18-subunit membrane-bound complex.
AB  - Biohydrogen gas has enormous potential as a source of reductant for the microbial
      production of biofuels, but its low solubility and poor gas mass transfer rates
      are limiting factors. These limitations could be circumvented by engineering
      biofuel production in microorganisms that are also capable of generating H2 from
      highly soluble chemicals such as formate, which can function as an electron
      donor. Herein, the model hyperthermophile, Pyrococcus furiosus, which grows
      optimally near 100  degrees C by fermenting sugars to produce H2, has been
      engineered to also efficiently convert formate to H2. Using a bacterial
      artificial chromosome vector, the 16.9-kb 18-gene cluster encoding the membrane
      bound, respiratory formate hydrogen lyase complex of Thermococcus onnurineus was
      inserted into the P. furiosus chromosome and expressed as a functional unit. This
      enabled P. furiosus to utilize formate as well as sugars as an H2 source and to
      do so at both 80 degrees  and 95  degrees C, near the optimum growth temperature
      of the donor (T. onnurineus) and engineered host (P. furiosus), respectively.
      This accomplishment also demonstrates the versatility of P. furiosus for
      metabolic engineering applications. 

PMID- 24318963
TI  - Signaling mechanisms of axon guidance and early synaptogenesis.
AB  - The development of the vertebrate nervous system, including the brain and spinal
      cord, progresses in a step-wise fashion that involves the function of thousands
      of genes. The birth of new neurons (also known as neurogenesis) and their
      subsequent migration to appropriate locations within the developing brain mark
      the earliest stages of CNS development. Subsequently, these newborn neurons
      extend axons and dendrites to make stereotyped synaptic connections within the
      developing brain, which is a complex process involving cell intrinsic mechanisms
      that respond to specific extracellular signals. The extension and navigation of
      the axon to its appropriate target region in the brain and body is dependent upon
      many cell surface proteins that detect extracellular cues and transduce signals
      to the inside of the cell. In turn, intracellular signaling mechanisms
      orchestrate axon structural reorganization and appropriate turning toward or away
      from a guidance cue. Once the target region is reached, chemical synapses are
      formed between the axon and target cell, and again, this appears to involve cell
      surface proteins signaling to the inside of the neuron to stabilize and mature a
      synapse. Here, we describe some of the key convergent and, in some cases,
      divergent molecular pathways that regulate axon guidance and synaptogenesis in
      early brain development. Mutations in genes involved in early brain wiring and
      synapse formation and pruning increase the risk for developing autism, further
      highlighting the relevance of brain development factors in the pathophysiology of
      neurodevelopmental disorders. 

PMID- 24318962
TI  - Liver transplantation for bile duct injury after open and laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Bile duct injury (BDI) after cholecystectomy is a serious
      complication. In a small subset of patients with BDI, failure of surgical or non
      surgical management might lead to acute or chronic liver failure. The aim of this
      study was to review the indications and outcome of liver transplantation (LT) for
      BDI after open and laparoscopic cholecystectomy. METHODS: Patients with BDI after
      cholecystectomy who were on the waiting list for LT between January 1987 and
      December 2010 were identified from LT centres in Spain. A standardized
      questionnaire was sent to each unit for extraction of data on diagnosis, previous
      treatments, indication and outcome of LT for BDI. RESULTS: Some 27 patients with
      BDI after cholecystectomy in whom surgical and non-surgical management for BDI
      failed were scheduled for LT over the 24-year interval. Emergency LT for acute
      liver failure was indicated in seven patients, all after laparoscopic
      cholecystectomy. Two patients died while on the waiting list and only one patient
      survived more than 30 days after LT. Elective LT for secondary biliary cirrhosis
      after a failed hepaticojejunostomy was performed in 13 patients after open and
      seven after laparoscopic cholecystectomy. One patient from the elective
      transplantation group died within 30 days of LT. The estimated 5-year overall
      survival rate was 68 per cent. CONCLUSION: Emergency LT for acute liver failure
      was more common in patients with BDI after laparoscopic cholecystectomy, and
      associated with a poor outcome.

PMID- 24318964
TI  - Cooperation came first: evolution and human cognition.
AB  - Contextual behavioral perspectives on learning and behavior reside under the
      umbrella of evolution science. In this paper we briefly review current
      developments in evolution science that bear on learning and behavior, concluding
      that behavior is now moving to the center of evolution studies. Learning is one
      of the main ladders of evolution by establishing functional benchmarks within
      which genetic adaptations can be advantaged. We apply that approach to the
      beginning feature of human cognition according to Relational Frame Theory:
      derived symmetry in coordination framing. When combined with the idea that
      cooperation came before major advances in human cognition or culture, existing
      abilities in social referencing, joint attention, perspective-taking skills, and
      relational learning ensure that the behavioral subcomponents of symmetrical
      equivalence relations would be reinforced. When coordination framing emerged and
      came under arbitrary contextual control as an operant class, a template was
      established for the development of multiple relational frames and the emergence
      and evolutionary impact of human cognition as we know it. Implications of these
      ideas for translational research are briefly discussed. 

PMID- 24318965
TI  - Identification of initially appearing glycine-immunoreactive neurons in the
      embryonic zebrafish brain.
AB  - Glycine is a major inhibitory neurotransmitter in the central nervous system of
      vertebrates. Here, we report the initial development of glycine-immunoreactive
      (Gly-ir) neurons and fibers in zebrafish. The earliest Gly-ir cells were found in
      the hindbrain and rostral spinal cord by 20 h post-fertilization (hpf). Gly-ir
      cells in rhombomeres 5 and 6 that also expressed glycine transporter 2 (glyt2)
      mRNA were highly stereotyped; they were bilaterally located and their axons ran
      across the midline and gradually turned caudally, joining the medial longitudinal
      fascicles in the spinal cord by 24 hpf. Gly-ir neurons in rhombomere 5 were
      uniquely identified, since there was one per hemisegment, whereas the number of
      Gly-ir neurons in rhombomere 6 were variable from one to three per hemisegment.
      Labeling of these neurons by single-cell electroporation and tracing them until
      the larval stage revealed that they became MiD2cm and MiD3cm, respectively. The
      retrograde labeling of reticulo-spinal neurons in Tg(glyt2:gfp) larva, which
      express GFP in Gly-ir cells, and a genetic mosaic analysis with glyt2:gfp DNA
      construct also supported this notion. Gly-ir cells were also distributed widely
      in the anterior brain by 27 hpf, whereas glyt2 was hardly expressed. Double
      staining with anti-glycine and anti-GABA antibodies demonstrated distinct
      distributions of Gly-ir and GABA-ir cells, as well as the presence of doubly
      immunoreactive cells in the brain and placodes. These results provide evidence of
      identifiable glycinergic (Gly-ir/glyt2-positive) neurons in vertebrate embryos,
      and they can be used in further studies of the neurons' development and function
      at the single-cell level.

PMID- 24318966
TI  - Water-dispersible, pH-stable and highly-luminescent organic dye nanoparticles
      with amplified emissions for in vitro and in vivo bioimaging.
AB  - A new strategy is presented for using doped small-molecule organic nanoparticles
      (NPs) to achieve high-performance fluorescent probes with strong brightness,
      large Stokes shifts and tunable emissions for in vitro and in vivo imaging. The
      host organic NPs are used not only as carriers to encapsulate different doped
      dyes, but also as fluorescence resonance energy transfer donors to couple with
      the doped dyes (as acceptors) to achieve multicolor luminescence with amplified
      emissions (AE). The resulting optimum green emitting NPs show high brightness
      with quantum yield (QY) of up to 45% and AE of 12 times; and the red emitting NPs
      show QY of 14% and AE of 10 times. These highly-luminescent doped NPs can be
      further surface modified with poly(maleic anhydride-alt-1-octadecene)
      polyethylene glycol (C18PMH-PEG), endowing them with excellent water
      dispersibility and robust stability in various bio-environments covering wide pH
      values from 2 to 10. In this study, cytotoxicity studies and folic acid targeted
      cellular imaging of these multicolor probes are carried out to demonstrate their
      potential for in vitro imaging. On this basis, applications of the NP probes in
      in vivo and ex vivo imaging are also investigated. Intense fluorescent signals of
      the doped NPs are distinctly, selectively and spatially resolved in tumor sites
      with high sensitivity, due to the preferential accumulation of the NPs in tumor
      sites through the passive enhanced permeability and retention effect. The results
      clearly indicate that these doped NPs are promising fluorescent probes for
      biomedical applications. 

PMID- 24318967
TI  - Activated 5'flanking region of NANOGP8 in a self-renewal environment is
      associated with increased sphere formation and tumor growth of prostate cancer
      cells.
AB  - INTRODUCTION: NANOGP8 is a retrogene which encodes a full-length protein similar
      to the NANOG1 gene. The expression of NANOGP8 has been documented in several
      cancers and is related to cell proliferation and tumor development. However, the
      regulation of NANOGP8 expression has not been investigated. Therefore, the role
      of NANOGP8 in cell proliferation has not been completely understood. METHODS: We
      evaluate the expression of NANOG1 and NANOGP8 in prostate cancer cell lines and
      primary cultures of prostate tissues. We investigate clonogenicity, sphere
      formation, and xenograft tumor growth of prostate cancer cells with an activated
      5'flanking region of NANOGP8. We examine the role of NANOGP8 in cell cycle
      progression. RESULTS: In the prostate cells the NANOG RNA was transcribed from
      NANOGP8 and not from NANOG1. Cells with the activated 5'flanking region of
      NANOGP8 exhibited enhanced clonogenicity, sphere formation, and xenograft tumor
      growth. The sphere culture and tumor initiation mouse mode promoted the
      activation of the 5'flanking region of NANOGP8. Forced expression of NANOGP8
      increased the entry into the cell cycle. DISCUSSION: In prostate cells NANOGP8 is
      a predominant molecule of NANOG. The activation of 5'flanking sequence of NANOGP8
      could play a role in the regulation of the stem-like properties of cancer stem
      cells and prostate tumor initiation and development. The microenvironment
      favoring cancer stem cells could promote the activation of the 5'flanking region
      of NANOGP8.

PMID- 24318968
TI  - Relationship between raised BMI and sugar sweetened beverage and high fat food
      consumption among children.
AB  - OBJECTIVE: Longitudinal evidence of relationships between unhealthy diets and BMI
      in children is crucial for appropriately targeting obesity prevention activities.
      The objective was to determine the relationship between frequency of consumption
      of sugar sweetened beverages (SSBs) and high fat foods (HFFs) and body weight in
      Australian children aged from 4 to 10 years. METHODS: Data from 4,164 children
      participating in four waves (wave 1, 2004; wave 2, 2006; wave 3, 2008; and wave
      4, 2010) of the Longitudinal Study of Australian Children were analyzed. A multi
      level growth model tested relationships between consumption of SSB and HFF and
      BMI z-scores. RESULTS: BMI z-scores were associated with daily consumption of
      HFF, SSB and maternal BMI independent of BMI z-scores at wave 1 (baseline); with
      each additional occurrence of SSB and HFF consumption intake per day, BMI z-score
      increased by 0.015 U (P < 0.01) and 0.014 U (P < 0.001), respectively. With each
      additional maternal BMI unit, BMI z-score increased by 0.032 (P < 0.001).
      CONCLUSIONS: Higher BMI z-scores were strongly associated with the consumption of
      SSBs and HFFs. Future efforts to prevent obesity should consider urgent action to
      address the impact of the consumption of SSBs and HFFs in childhood.

PMID- 24318969
TI  - Sequence, biophysical, and structural analyses of the PstS lipoprotein (BB0215)
      from Borrelia burgdorferi reveal a likely binding component of an ABC-type
      phosphate transporter.
AB  - The Lyme disease agent Borrelia burgdorferi, which is transmitted via a tick
      vector, is dependent on its tick and mammalian hosts for a number of essential
      nutrients. Like other bacterial diderms, it must transport these biochemicals
      from the extracellular milieu across two membranes, ultimately to the B.
      burgdorferi cytoplasm. In the current study, we established that a gene cluster
      comprising genes bb0215 through bb0218 is cotranscribed and is therefore an
      operon. Sequence analysis of these proteins suggested that they are the
      components of an ABC-type transporter responsible for translocating phosphate
      anions from the B. burgdorferi periplasm to the cytoplasm. Biophysical
      experiments established that the putative ligand-binding protein of this system,
      BbPstS (BB0215), binds to phosphate in solution. We determined the high
      resolution (1.3 A) crystal structure of the protein in the absence of phosphate,
      revealing that the protein's fold is similar to other phosphate-binding proteins,
      and residues that are implicated in phosphate binding in other such proteins are
      conserved in BbPstS. Taken together, the gene products of bb0215-0218 function as
      a phosphate transporter for B. burgdorferi. 

PMID- 24318970
TI  - Matrilysin-2 expression in colorectal cancer is associated with overall survival
      of patients.
AB  - Tumor recurrence and metastasis are pressing issues of patients with colorectal
      cancer who receive surgery. Matrilysin-2 (MMP-26) has been proved to play an
      important role during invasion and metastasis of some human solid tumor. We aimed
      to investigate the clinical significance and prognostic value of matrilysin-2 in
      human colorectal cancer. Colorectal cancer and adjacent normal samples from 201
      patients were collected. Matrilysin-2 expression level was investigated by
      immunohistochemistry assay, and its association with overall survival of patients
      was analyzed by statistical analysis. Results showed that matrilysin-2 expression
      level significantly elevated in colorectal cancer compared with adjacent normal
      specimens. Matrilysin-2 expression was also found to be associated with cancer
      invasion, lymph node metastasis, distant metastasis, and TNM stage. In addition,
      survival analysis showed that elevated matrilysin-2 expression was associated
      with poor overall survival of patients. Cox's proportional hazards model
      indicated that matrilysin-2 was an independent prognostic marker for patients
      with colorectal cancer. The present study found that the expression of matrilysin
      2 increased in colorectal cancer and was associated with tumor progression. It
      also provided the first evidence that matrilysin-2 expression was an independent
      prognostic factor for patients with colorectal cancer, which might be a high
      specific biomarker for colorectal cancer. 

PMID- 24318971
TI  - STAG2 expression in oral cancer and potentially malignant lesions.
AB  - Oral cancer is a world health problem, and one of the highest incidence rates of
      oral cancer worldwide occurs in Brazil. STAG2 is part of the cohesin complex
      which is responsible for sister chromatid cohesion. STAG2 loss of expression was
      reported in a range of tumors, and STAG2 loss was found to cause chromosomal
      instability and aneuploidy in cancer cells. On the basis of these findings, we
      investigated STAG2 expression in oral cancer and potentially malignant lesions.
      We investigated STAG2 immunoexpression in oral cancer, lip cancer, oral
      leukoplakia, and actinic cheilitis, including complete clinical information.
      Normal oral mucosa samples were included as normal controls. STAG2 protein was
      highly expressed in all samples. We further tested STAG2 expression in gastric
      adenocarcinomas and glioblastomas, as these tumor types were previously shown to
      lose STAG2 expression. We found homogenous expression of STAG2 by these tumor
      cells. Our results suggest that STAG2 loss of expression is not a common event in
      oral carcinogenesis. 

PMID- 24318972
TI  - Lack of association between interleukin-4 -524C>T polymorphism and colorectal
      cancer susceptibility.
AB  - Interleukin-4 (IL-4) -524C > T polymorphism has been implicated to alter the risk
      of colorectal cancer (CRC), but the results are controversial. The objective of
      this study was to quantitatively evaluate the association between IL-4 -524C > T
      polymorphism and CRC risk. A comprehensive search was conducted to identify all
      eligible studies of IL-4 -524C > T polymorphism and CRC risk. Statistical
      analysis was performed with Review Manager 5.0 and Stata 11. A total of 5 case
      control studies, including 1,224 cases and 1,551 controls, were included. The
      combined results based on all eligible studies suggested that IL-4 -524C > T
      polymorphism was not associated with CRC susceptibility. When stratifying for
      race, the data showed that the IL-4 -524C > T polymorphism was also not
      associated with an increased CRC susceptibility in Caucasians. Our study suggests
      that IL-4 -524C > T polymorphism may be not associated with an increased CRC
      susceptibility.

PMID- 24318974
TI  - The phenomenon of voltage controlled switching in disordered superconductors.
AB  - The superconductor-to-insulator transition (SIT) is a phenomenon occurring in
      highly disordered superconductors and may be useful in the development of
      superconducting switches. The SIT has been demonstrated to be induced by
      different external parameters: temperature, magnetic field, electric field, etc.
      However, the electric field induced SIT (ESIT), which has been experimentally
      demonstrated for some specific materials, holds particular promise for practical
      device development. Here, we demonstrate, from theoretical considerations, the
      occurrence of the ESIT. We also propose a general switching device architecture
      using the ESIT and study some of its universal behavior, such as the effects of
      sample size, disorder strength and temperature on the switching action. This work
      provides a general framework for the development of such a device. 

PMID- 24318973
TI  - Clinical significance of S100A2 expression in gastric cancer.
AB  - Gastric carcinoma (GC) is one of the most common malignancies worldwide. To
      identify the candidate carcinoma-related biomarker in GC, comparative proteome
      technique was performed in resected GC tissues and matched adjacent non-cancerous
      gastric tissues (ANGT). As a result, S100A2 was successfully identified to be
      down-regulated significantly in GC compared with ANGT. Western blot analysis
      validated decreased expression of S100A2, and its expression level was related
      with the degree of tumor differentiation and status of lymph node metastasis in
      GC. Furthermore, immunohistochemistry analysis showed S100A2 down-expression was
      significantly associated with poor differentiation (P < 0.05), advanced depth of
      invasion (P < 0.05) and lymph node metastasis (P < 0.05) in GC. Kaplan-Meier
      curves showed that the relapse-free probability and the overall survival rate
      were significantly decreased with S100A2 expression decreasing (P < 0.05). Cox
      regression analysis indicated S100A2 down-expression was a negative independent
      prognostic biomarker for GC. A supplement of S100A2 protein by S100A2 expression
      vector significantly decreased the number of invaded cancer cells MGC-803.
      However, knockdown of S100A2 expression by siRNA interference compromised the
      invasion ability of MGC-803 cells. Moreover, S100A2 negatively regulated MEK/ERK
      signaling pathway, and activation of this signaling pathway by S100A2 down
      regulation increased in vitro invasion of MGC-803 cells. In conclusion, this
      study demonstrated the clinical significance of S100A2 expression in GC, and loss
      of S100A2 expression contributes to GC development and progression. Therefore,
      the determination of S100A2 expression levels contributes to predict the outcome
      of GC patients.

PMID- 24318975
TI  - Neoplasms of the urinary tract in fish.
AB  - The veterinary literature contains scattered reports of primary tumors of the
      urinary tract of fish, dating back to 1906. Many of the more recent reports have
      been described in association with the Registry of Tumors in Lower Animals, and
      most of the spontaneous neoplasms of the kidney and urinary bladder are single
      case reports. In rare instances, such as described in nephroblastomas of Japanese
      eels and tubular adenomas/adenocarcinomas of Oscars, there is suggestion of a
      genetic predisposition of certain populations to specific renal neoplasms,
      environmental carcinogenesis, or potentially an unknown infectious etiology
      acting as a promoter. Hematopoeitic neoplasms have been infrequently described as
      primary to the kidney of a variety of fish species, and therefore those case
      reports of renal lymphoma and plasmacytic leukemia are addressed within the
      context of this review. 

PMID- 24318976
TI  - Horizontally transferred genetic elements and their role in pathogenesis of
      bacterial disease.
AB  - This article reviews the roles that laterally transferred genes (LTG) play in the
      virulence of bacterial pathogens. The features of LTG that allow them to be
      recognized in bacterial genomes are described, and the mechanisms by which LTG
      are transferred between and within bacteria are reviewed. Genes on plasmids,
      integrative and conjugative elements, prophages, and pathogenicity islands are
      highlighted. Virulence genes that are frequently laterally transferred include
      genes for bacterial adherence to host cells, type 3 secretion systems, toxins,
      iron acquisition, and antimicrobial resistance. The specific roles of LTG in
      pathogenesis are illustrated by specific reference to Escherichia coli,
      Salmonella, pyogenic streptococci, and Clostridium perfringens. 

PMID- 24318977
TI  - Six-term transitive inference with pigeons: successive-pair training followed by
      mixed-pair training.
AB  - In nonhuman animals, the transitive inference (TI) task typically involves
      training a series of four simultaneous discriminations involving, for example,
      arbitrary colors in which choice of one stimulus in each pair is reinforced [+]
      and choice of the other color is nonreinforced [-]. This can be represented as
      A+B-, B+C-, C+D-, D+E- and can be conceptualized as a series of linear
      relationships: A > B > C > D > E. After training, animals are tested on the
      untrained non-endpoint pair, BD. Preference for B over D is taken as evidence of
      TI and occurs because B is greater than D in the implied series. In the present
      study we trained pigeons using a novel training procedure-a hybrid of successive
      pair training (training one pair at a time) and mixed-pair training (training all
      pairs at once)-designed to overcome some of the limitations of earlier
      procedures. Using this hybrid procedure, we trained five premise pairs (A+B-, B+C
      , C+D-, D+E-, and E+F-) which allowed us to test three untrained non-endpoint
      pairs (BD, CE, and BE). A significant TI effect was found for most subjects on at
      least two out of three test pairs. Different theories of TI are discussed. The
      results suggest that this hybrid training is an efficient procedure for
      establishing mixed-pair acquisition and a TI effect.

PMID- 24318978
TI  - Developmental expression of the calcium-activated chloride channels TMEM16A and
      TMEM16B in the mouse olfactory epithelium.
AB  - Calcium-activated chloride channels are involved in several physiological
      processes including olfactory perception. TMEM16A and TMEM16B, members of the
      transmembrane protein 16 family (TMEM16), are responsible for calcium-activated
      chloride currents in several cells. Both are present in the olfactory epithelium
      of adult mice, but little is known about their expression during embryonic
      development. Using immunohistochemistry we studied their expression in the mouse
      olfactory epithelium at various stages of prenatal development from embryonic day
      (E) 12.5 to E18.5 as well as in postnatal mice. At E12.5, TMEM16A
      immunoreactivity was present at the apical surface of the entire olfactory
      epithelium, but from E16.5 became restricted to a region near the transition zone
      with the respiratory epithelium, where localized at the apical part of supporting
      cells and in their microvilli. In contrast, TMEM16B immunoreactivity was present
      at E14.5 at the apical surface of the entire olfactory epithelium, increased in
      subsequent days, and localized to the cilia of mature olfactory sensory neurons.
      These data suggest different functional roles for TMEM16A and TMEM16B in the
      developing as well as in the postnatal olfactory epithelium. The presence of
      TMEM16A at the apical part and in microvilli of supporting cells is consistent
      with a role in the regulation of the chloride ionic composition of the mucus
      covering the apical surface of the olfactory epithelium, whereas the localization
      of TMEM16B to the cilia of mature olfactory sensory neurons is consistent with a
      role in olfactory signal transduction.

PMID- 24318979
TI  - RAISE - rheumatoid arthritis independent Swiss treatment expectations and
      outcome: results for the abatacept subpopulation.
AB  - QUESTIONS UNDER STUDY: Clinical trials do not necessarily reflect the results
      obtained in daily clinical practice. By conducting a non-interventional,
      observational study with biologics in rheumatoid arthritis (RA) patients in
      Switzerland, we aimed to generate real-world data on reasons for treatment
      initiation and discontinuation, physicians' expectations for treatment, co
      medication, and various treatment outcome parameters. METHODS: Sixty-nine
      patients with a confirmed diagnosis of RA were included in this non
      interventional observational study. Participating physicians used standardised
      questionnaires to collect data on the use of biologics at three visits over one
      year. Due to the small sample size of patients receiving biologics other than
      abatacept, only patients treated with abatacept were considered for analysis.
      RESULTS: The population receiving intravenously administered abatacept consisted
      of 56 patients. Of these, 25% received abatacept as a first-line biologic
      therapy. The retention rate over one year was high (75%) and similar to what has
      been previously observed in randomised clinical trials. Overall, abatacept was
      found to be effective in patients irrespective of their baseline disease activity
      or levels in C-reactive protein and erythrocyte sedimentation rate. Moreover, the
      use of glucocorticoids was found to be reduced under therapy. There was a
      tendency for better treatment outcomes and physicians' satisfaction with
      abatacept the earlier the drug was used in the sequence of biologic therapies.
      CONCLUSIONS: The present study suggests that abatacept is an effective and well
      tolerated treatment in RA patients in routine clinical practice, irrespective of
      disease parameter at baseline.

PMID- 24318980
TI  - Flexible memory retrieval in bilingual 6-month-old infants.
AB  - Memory flexibility is a hallmark of the human memory system. As indexed by
      generalization between perceptually dissimilar objects, memory flexibility
      develops gradually during infancy. A recent study has found a bilingual advantage
      in memory generalization at 18 months of age [Brito and Barr [2012] Developmental
      Science, 15, 812-816], and the present study examines when this advantage may
      first emerge. In the current study, bilingual 6-month-olds were more likely than
      monolinguals to generalize to a puppet that differed in two features (shape and
      color) than monolingual 6-month-olds. When challenged with a less complex change,
      two puppets that differed only in one feature--color, monolingual 6-month-olds
      were also able to generalize. These findings demonstrate early emerging
      differences in memory generalization in bilingual infants, and have important
      implications for our understanding of how early environmental variations shape
      the trajectory of memory development.

PMID- 24318981
TI  - Diagnosis of minimal hepatic encephalopathy in patients with cirrhosis: should we
      bury psychometric tests?

PMID- 24318982
TI  - Binding of HIV-1 Vpr protein to the human homolog of the yeast DNA repair protein
      RAD23 (hHR23A) requires its xeroderma pigmentosum complementation group C binding
      (XPCB) domain as well as the ubiquitin-associated 2 (UBA2) domain.
AB  - The human homolog of the yeast DNA repair protein RAD23, hHR23A, has been found
      previously to interact with the human immunodeficiency virus, type 1 accessory
      protein Vpr. hHR23A is a modular protein containing an N-terminal ubiquitin-like
      (UBL) domain and two ubiquitin-associated domains (UBA1 and UBA2) separated by a
      xeroderma pigmentosum complementation group C binding (XPCB) domain. All domains
      are connected by flexible linkers. hHR23A binds ubiquitinated proteins and acts
      as a shuttling factor to the proteasome. Here, we show that hHR23A utilizes both
      the UBA2 and XPCB domains to form a stable complex with Vpr, linking Vpr directly
      to cellular DNA repair pathways and their probable exploitation by the virus.
      Detailed structural mapping of the Vpr contacts on hHR23A, by NMR, revealed
      substantial contact surfaces on the UBA2 and XPCB domains. In addition, Vpr
      binding disrupts an intramolecular UBL-UBA2 interaction. We also show that Lys-48
      linked di-ubiquitin, when binding to UBA1, does not release the bound Vpr from
      the hHR23A-Vpr complex. Instead, a ternary hHR23A.Vpr.di-Ub(K48) complex is
      formed, indicating that Vpr does not necessarily abolish hHR23A-mediated
      shuttling to the proteasome. 

PMID- 24318983
TI  - Deletion of the cardiolipin-specific phospholipase Cld1 rescues growth and life
      span defects in the tafazzin mutant: implications for Barth syndrome.
AB  - Cardiolipin (CL) that is synthesized de novo is deacylated to monolysocardiolipin
      (MLCL), which is reacylated by tafazzin. Remodeled CL contains mostly unsaturated
      fatty acids. In eukaryotes, loss of tafazzin leads to growth and respiration
      defects, and in humans, this results in the life-threatening disorder Barth
      syndrome. Tafazzin deficiency causes a decrease in the CL/MLCL ratio and
      decreased unsaturated CL species. Which of these biochemical outcomes contributes
      to the physiological defects is not known. Yeast cells have a single CL-specific
      phospholipase, Cld1, that can be exploited to distinguish between these outcomes.
      The cld1Delta mutant has decreased unsaturated CL, but the CL/MLCL ratio is
      similar to that of wild type cells. We show that cld1Delta rescues growth, life
      span, and respiratory defects of the taz1Delta mutant. This suggests that
      defective growth and respiration in tafazzin-deficient cells are caused by the
      decreased CL/MLCL ratio and not by a deficiency in unsaturated CL. CLD1
      expression is increased during respiratory growth and regulated by the heme
      activator protein transcriptional activation complex. Overexpression of CLD1
      leads to decreased mitochondrial respiration and growth and instability of
      mitochondrial DNA. However, ATP concentrations are maintained by increasing
      glycolysis. We conclude that transcriptional regulation of Cld1-mediated
      deacylation of CL influences energy metabolism by modulating the relative
      contribution of glycolysis and respiration. 

PMID- 24318985
TI  - Genome network medicine: innovation to overcome huge challenges in cancer
      therapy.
AB  - The post-ENCODE era shapes now a new biomedical research direction for
      understanding transcriptional and signaling networks driving gene expression and
      core cellular processes such as cell fate, survival, and apoptosis. Over the past
      half century, the Francis Crick 'central dogma' of single n gene/protein
      phenotype (trait/disease) has defined biology, human physiology, disease,
      diagnostics, and drugs discovery. However, the ENCODE project and several other
      genomic studies using high-throughput sequencing technologies, computational
      strategies, and imaging techniques to visualize regulatory networks, provide
      evidence that transcriptional process and gene expression are regulated by highly
      complex dynamic molecular and signaling networks. This Focus article describes
      the linear experimentation-based limitations of diagnostics and therapeutics to
      cure advanced cancer and the need to move on from reductionist to network-based
      approaches. With evident a wide genomic heterogeneity, the power and challenges
      of next-generation sequencing (NGS) technologies to identify a patient's personal
      mutational landscape for tailoring the best target drugs in the individual
      patient are discussed. However, the available drugs are not capable of targeting
      aberrant signaling networks and research on functional transcriptional
      heterogeneity and functional genome organization is poorly understood. Therefore,
      the future clinical genome network medicine aiming at overcoming multiple
      problems in the new fields of regulatory DNA mapping, noncoding RNA, enhancer
      RNAs, and dynamic complexity of transcriptional circuitry are also discussed
      expecting in new innovation technology and strong appreciation of clinical data
      and evidence-based medicine. The problematic and potential solutions in the
      discovery of next-generation, molecular, and signaling circuitry-based biomarkers
      and drugs are explored.

PMID- 24318984
TI  - Challenging the state of the art in protein structure prediction: Highlights of
      experimental target structures for the 10th Critical Assessment of Techniques for
      Protein Structure Prediction Experiment CASP10.
AB  - For the last two decades, CASP has assessed the state of the art in techniques
      for protein structure prediction and identified areas which required further
      development. CASP would not have been possible without the prediction targets
      provided by the experimental structural biology community. In the latest
      experiment, CASP10, more than 100 structures were suggested as prediction
      targets, some of which appeared to be extraordinarily difficult for modeling. In
      this article, authors of some of the most challenging targets discuss which
      specific scientific question motivated the experimental structure determination
      of the target protein, which structural features were especially interesting from
      a structural or functional perspective, and to what extent these features were
      correctly reproduced in the predictions submitted to CASP10. Specifically, the
      following targets will be presented: the acid-gated urea channel, a difficult to
      predict transmembrane protein from the important human pathogen Helicobacter
      pylori; the structure of human interleukin (IL)-34, a recently discovered helical
      cytokine; the structure of a functionally uncharacterized enzyme OrfY from
      Thermoproteus tenax formed by a gene duplication and a novel fold; an ORFan
      domain of mimivirus sulfhydryl oxidase R596; the fiber protein gene product 17
      from bacteriophage T7; the bacteriophage CBA-120 tailspike protein; a virus coat
      protein from metagenomic samples of the marine environment; and finally, an
      unprecedented class of structure prediction targets based on engineered disulfide
      rich small proteins.

PMID- 24318986
TI  - The critical role of the loops of triosephosphate isomerase for its
      oligomerization, dynamics, and functionality.
AB  - Triosephosphate isomerase (TIM) catalyzes the reaction to convert
      dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, and vice versa. In
      most organisms, its functional oligomeric state is a homodimer; however, tetramer
      formation in hyperthermophiles is required for functional activity. The
      tetrameric TIM structure also provides added stability to the structure, enabling
      it to function at more extreme temperatures. We apply Principal Component
      Analysis to find that the TIM structure space is clearly divided into two groups-
      the open and the closed TIM structures. The distribution of the structures in the
      open set is much sparser than that in the closed set, showing a greater
      conformational diversity of the open structures. We also apply the Elastic
      Network Model to four different TIM structures--an engineered monomeric
      structure, a dimeric structure from a mesophile--Trypanosoma brucei, and two
      tetrameric structures from hyperthermophiles Thermotoga maritima and Pyrococcus
      woesei. We find that dimerization not only stabilizes the structures, it also
      enhances their functional dynamics. Moreover, tetramerization of the
      hyperthermophilic structures increases their functional loop dynamics, enabling
      them to function in the destabilizing environment of extreme temperatures.
      Computations also show that the functional loop motions, especially loops 6 and
      7, are highly coordinated. In summary, our computations reveal the underlying
      mechanism of the allosteric regulation of the functional loops of the TIM
      structures, and show that tetramerization of the structure as found in the
      hyperthermophilic organisms is required to maintain the coordination of the
      functional loops at a level similar to that in the dimeric mesophilic structure.

PMID- 24318987
TI  - In dogs we trust? Intersubjectivity, response-able relations, and the making of
      mine detector dogs.
AB  - The utility of the dog as a mine detector has divided the mine clearance
      community since dogs were first used for this purpose during the Second World
      War. This paper adopts a historical perspective to investigate how, why, and to
      what consequence, the use of minedogs remains contested despite decades of
      research into their abilities. It explores the changing factors that have made it
      possible to think that dogs could, or could not, serve as reliable detectors of
      landmines over time. Beginning with an analysis of the wartime context that
      shaped the creation of minedogs, the paper then examines two contemporaneous
      investigations undertaken in the 1950s. The first, a British investigation
      pursued by the anatomist Solly Zuckerman, concluded that dogs could never be the
      mine hunter's best friend. The second, an American study led by the
      parapsychologist J. B. Rhine, suggested dogs were potentially useful for mine
      clearance. Drawing on literature from science studies and the emerging
      subdiscipline of "animal studies," it is argued that cross-species
      intersubjectivity played a significant role in determining these different
      positions. The conceptual landscapes of Zuckerman and Rhine's disciplinary
      backgrounds are shown to have produced distinct approaches to managing cross
      species relations, thus explaining how diverse opinions on minedog can coexist.
      In conclusion, it is shown that the way one structures relationships between
      humans and animals has profound impact on the knowledge and labor subsequently
      produced, a process that cannot be separated from ethical consequence.

PMID- 24318988
TI  - FUT11 as a potential biomarker of clear cell renal cell carcinoma progression
      based on meta-analysis of gene expression data.
AB  - In this paper, we provide a comprehensive summary of available clear cell renal
      cell carcinoma (ccRCC) microarray data in the form of meta-analysis of genes
      differentially regulated in tumors as compared to healthy tissue, using effect
      size to measure the strength of a relationship between the disease and gene
      expression. We identified 725 differentially regulated genes, with a number of
      interesting targets, such as TMEM213, SMIM5, or ATPases: ATP6V0A4 and ATP6V1G3,
      of which limited or no information is available in terms of their function in
      ccRCC pathology. Downregulated genes tended to represent pathways related to
      tissue remodeling, blood clotting, vasodilation, and energy metabolism, while
      upregulated genes were classified into pathways generally deregulated in cancers:
      immune system response, inflammatory response, angiogenesis, and apoptosis. One
      hundred fifteen deregulated genes were included in network analysis, with EGLN3,
      AP-2, NR3C1, HIF1A, and EPAS1 (gene encoding HIF2-alpha) as points of functional
      convergence, but, interestingly, 610 genes failed to join previously identified
      molecular networks. Furthermore, we validated the expression of 14 top
      deregulated genes in independent sample set of 32 ccRCC tumors by qPCR and tested
      if it could serve as a marker of disease progression. We found a correlation of
      high fucosyltransferase 11 (FUT11) expression with non-symptomatic course of the
      disease, which suggests that FUT11's expression might be potentially used as a
      biomarker of disease progression. 

PMID- 24318989
TI  - Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric
      cancer treated with FOLFOX-based chemotherapy.
AB  - Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision
      repair cross-complimentary group 4 (ERCC4) genes have been implicated in the
      prognosis of various cancers. We conducted a cohort study to investigate the role
      of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of
      these two gene polymorphisms on the clinical outcomes of gastric cancer. Four
      hundred forty-seven patients with newly diagnosed and histopathologically
      confirmed primary gastric cancer were collected in our study and were followed up
      until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4
      (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall
      chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and
      T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly
      higher response rate to the chemotherapy. In the Cox proportional hazard model,
      the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1
      rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94),
      respectively. Similarly, we found a significant decreased risk of death from
      gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele
      when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were
      0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals
      carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold
      risk of death from gastric cancer. This study reported a carriage of ERCC1
      rs11615, and rs2298881 polymorphism can be used as a predictor of response to
      folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in
      gastric cancer patients.

PMID- 24318990
TI  - GSTM1 null genotype is associated with increased risk of gastric cancer in both
      ever-smokers and non-smokers: a meta-analysis of case-control studies.
AB  - Previous studies have suggested that the glutathione S-transferases M1 (GSTM1)
      null genotype is associated with the risk of gastric cancer. However, the
      interaction between GSTM1 null genotype and smoking for the risk of gastric
      cancer is still elusive. Therefore, we performed a meta-analysis to ascertain
      this issue. Databases of PubMed, EMBASE, and China National Knowledge
      Infrastructure were searched to retrieve relevant studies. Smokers were
      categorized as "ever-smokers" and "non-smokers." Odds ratios (ORs) and 95%
      confidence intervals (95% CIs) were calculated to estimate the association
      strength. Subgroup analyses according to ethnicity, source of control, and sample
      size were also conducted. A total of 15 eligible studies, including 4,687 gastric
      cancer cases and 7,002 controls, were identified. We found that the GSTM1 null
      genotype was associated with increased risk of gastric cancer among ever-smokers
      (OR = 1.460, 95% CI 1.064-2.003, heterogeneity: P = 0.019). The null genotype
      also significantly increased the risk of gastric cancer among non-smokers (OR =
      1.777, 95% CI 1.301-2.426, heterogeneity: P < 0.01). Stratified analysis
      according to ethnicity showed that the GSTM1 null genotype was associated with
      increased risk of gastric cancer among Asians both in ever-smokers (OR = 1.841,
      95% CI 1.184-2.861) and non-smokers (OR = 1.773, 95% CI 1.382-2.275). In
      conclusion, the GSMT1 null genotype significantly increased the risk of gastric
      cancer both in ever-smokers and non-smokers.

PMID- 24318991
TI  - FokI polymorphism in vitamin D receptor gene and risk of breast cancer among
      Caucasian women.
AB  - Vitamin D plays a central role in cellular proliferation, apoptosis induction,
      and tumor growth suppression. The vitamin D receptor (VDR) is a crucial mediator
      for the cellular effects of vitamin D. A series of epidemiological studies have
      examined the association between the VDR FokI polymorphism and breast cancer
      risk, but the findings remain inconclusive. Fifteen eligible case-control studies
      involving 15,681 cancer cases and 20,632 control subjects were identified through
      searching PubMed, Embase, and Web of Science. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were used to assess the association. Heterogeneity
      across studies was examined with the chi-square-based Q test and the I (2) index.
      Begg's and Egger's test were also performed to determine publication bias. All
      statistical data were analyzed by STATA software. The combined estimates did not
      show significant risks correlated with the FokI polymorphism. However, we found
      an increased risk in the subgroup analysis by source of control (OR = 1.11, 95%
      CI = 1.01-1.22; heterogeneity test: P = 0.116, I(2) = 0.0% for ff vs FF; OR =
      1.10, 95% CI = 1.01-1.21; heterogeneity test: P = 0.832, I(2) = 0.0% for ff vs Ff
      + FF). This meta-analysis suggests that the presence of FokI polymorphism may
      contribute to the risk of breast cancer in Caucasians.

PMID- 24318993
TI  - Walker 256/B malignant breast cancer cells improve femur angioarchitecture and
      disrupt hematological parameters in a rat model of tumor osteolysis.
AB  - This study was designed to assess femur angioarchitecture and hematological
      effects of Walker 256/B cells in a rat model of tumor osteolysis. Tumor
      osteolysis was induced by in situ inoculation of Walker 256/B malignant cells.
      Six other rats were sham operated and served as control. Twenty days later, rats
      were euthanized, and femurs were collected than radiographed. Angioarchitecture
      [mean lumen diameter (MLD), wall thickness (WTh), Vessel number, volume, and
      separation (VNb, VV, and VSp respectively)] was studied by histomorphometry at 2
      different positions (P1: diaphysis, and P2: metaphysis) of the operated femora.
      Some hematological parameters were also assessed. Walker 256/B induced marked
      tumor osteolysis, with cortical perforation and trabecular destruction,
      associated increase in bone vascularization (increases of VNb and VV and decrease
      of VSp). Angioarchitecture of W256/B rats was disorganized and showed large MLD
      and lower WTh. These effects were more prominent in P2. When compared to Sham
      group, significantly decreases at levels of red blood cell (RBC), hemoglobin
      (Hb), hematocrit (Ht), and white blood cell (WBC) were observed in W256/B rats.
      These results suggest that Walker 256/B cells induced tumor osteolysis, improve
      hypervasculature especially near the tumoral foci (P2) associated hematological
      disruption. Besides, tumor vessels showed abnormal (enlarged and thinner) and
      disorganized morphology. 

PMID- 24318992
TI  - Association of IL-6 polymorphisms with hepatocellular carcinoma risk: evidences
      from a meta-analysis.
AB  - The associations between IL-6 gene single nucleotide polymorphisms (SNPs) and
      risk of hepatocellular carcinoma (HCC) are controversial. We performed a meta
      analysis to provide more credible evidence. We searched for relevant studies
      published up to 2013 by performing an efficient searching strategy. Odds ratios
      (OR) with 95% confidence interval (95% CI) was used to estimate the strength of
      the associations between IL-6 polymorphisms and HCC risk. We identified eight
      case-control studies involving 1,448 HCC cases and 3,160 controls. Our estimation
      specifically focused on two SNPs of the IL-6 gene, -174 G/C and -572 G/C. The
      combined results showed that association between IL-6-174 G/C polymorphism and
      risk of HCC was significant under additive model (CC vs. GG: OR 0.36; 95% CI,
      0.16, 0.85) and recessive model (GG+CG vs. CC: OR 2.82; 95% CI 1.26, 6.28).
      However, the IL-6-572 G/C polymorphism was not associated with HCC risk. In
      conclusion, IL-6-174 G/C, but not -572 G/C polymorphism could be a candidate for
      susceptibility to HCC. However, the results should be cautiously interpreted due
      to the limited number of the included studies.

PMID- 24318995
TI  - Notice of retraction.

PMID- 24318994
TI  - Liver cancer-related gene CYP2E1 expression in HBV transgenic mice with acute
      liver injury.
AB  - The objective of this research was to study the CYP2E1 gene expression in carbon
      tetrachloride (CCl4)-induced acute liver injury in hepatitis B virus (HBV)
      transgenic mice. Twenty-four HBV(-) and 24 HBV(+) transgenic mice aged 8 to 10
      weeks were selected for the present study. Intraperitoneal injection of 1.0 MUL/g
      of CCl4 (1:4 dissolved in olive oil) to mice was performed to induce acute liver
      injury model. Eight normal clean-grade C57BL/6 mice were taken as the control
      group. The control group received saline intraperitoneally. The mice in each
      group were killed 3, 6, 12, 24, 48, and 72 h after injection. The liver tissue
      samples of mice were collected. The liver histological changes at different time
      points in each group were observed under light microscope. The quantitative PCR
      methods were utilized to measure the relative mRNA levels of CYP2E1 gene in liver
      tissues. Immunohistochemistry and Western blot techniques were used to observe
      tissue expression levels of CYP2E1 in each group. Compared with that of the
      control group, mRNA and protein expression levels of CYP2E1 significantly
      increased both in the HBV(-) group and in the HBV(+) group after the CCl4 induced
      the acute liver injury, and it reached the peak at 72h after the CCl4 injection.
      Compared with the HBV(-) group, the mice in the HBV(+) group had severe liver
      damage and significantly increased CYP2E1 gene and protein expression levels. In
      the CCl4-induced acute liver injury of HBV transgenic mice, the CYP2E1 gene
      expression significantly increased. The results provided evidence for the HBV
      induced liver damage and liver cancer pathogenesis.

PMID- 24318996
TI  - Formation of hepatic DNA adducts by methyleugenol in mouse models: drastic
      decrease by Sult1a1 knockout and strong increase by transgenic human SULT1A1/2.
AB  - Methyleugenol--a natural constituent of herbs and spices--is hepatocarcinogenic
      in rodent models. It can form DNA adducts after side-chain hydroxylation and
      sulfation. We previously demonstrated that human sulfotransferases (SULTs) 1A1
      and 1A2 as well as mouse Sult1a1, expressed in Salmonella target strains, are
      able to activate 1'-hydroxymethyleugenol (1'-OH-ME) and 3'
      hydroxymethylisoeugenol (3'-OH-MIE) to mutagens. Now we investigated the role of
      these enzymes in the formation of hepatic DNA adducts by methyleugenol in the
      mouse in vivo. We used FVB/N mice [wild-type (wt)] and genetically modified
      strains in this background: Sult1a1 knockout (ko), transgenic for human SULT1A1/2
      (tg) and the combination of both modifications (ko-tg). Methyleugenol (50mg/kg
      body mass) formed 23, 735, 3770 and 4500 N (2)-(trans-methylisoeugenol-3'-yl)-2'
      deoxyguanosine adducts per 10(8) 2'-deoxyribonucleosides (dN) in ko, wt, ko-tg
      and tg mice, respectively. The corresponding values for an equimolar dose of 1'
      OH-ME were 12, 1490, 12 400 and 13 300 per 10(8) dN. Similar relative levels were
      observed for the minor adduct, N (6)-(trans-methylisoeugenol-3'-yl)-2'
      deoxyadenosine. Thus, the adduct formation by both compounds was nearly
      completely dependent on the presence of SULT1A enzymes, with human SULT1A1/2
      producing stronger effects than mouse Sult1a1. Moreover, a dose of 0.05 mg/kg
      methyleugenol (one-fourth of the estimated average daily exposure of humans) was
      sufficient to form detectable adducts in humanized (ko-tg) mice. Although 3'-OH
      MIE was equally mutagenic to 1'-OH-ME in Salmonella strains expressing human
      SULT1A1 or 1A2, it only formed 0.14% of hepatic adducts in ko-tg mice compared
      with an equimolar dose of 1'-OH-ME, suggesting an important role of detoxifying
      pathways for this isomer in vivo.

PMID- 24318997
TI  - Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in
      cancer cells and promote redox adaptation.
AB  - CD44 is frequently overexpressed in a wide variety of epithelial malignancies
      including gastrointestinal cancer and causes resistance to currently available
      treatments. MicroRNAs (miRNAs) are non-coding RNAs that regulate molecular
      pathways in cancer by targeting various genes. The aim of this study was to
      investigate the regulation of CD44 expression by miRNAs and to develop new
      molecular targets in gastrointestinal cancer. We performed miRNA screening in six
      human gastrointestinal cancer cell lines and identified three candidate miRNAs
      that could regulate CD44 expression in gastrointestinal cancer. Among these, we
      focused on miR-328 and examined its functional relevance using growth assays and
      cytotoxicity assays. CD44 expression was reduced in gastrointestinal cancer cell
      lines forced to express miR-328, leading to inhibition of cancer cell growth in
      vitro and in vivo, and impaired resistance to chemotherapeutic drugs and reactive
      oxygen species (ROS). In contrast, induction of CD44 expression by miR-328
      inhibitor led to promotion of cancer cell growth. Furthermore, we revealed that
      ROS produced by macrophages triggered CD44 expression through suppression of miR
      328 in gastric cancer cells. Finally, tumor-infiltrating macrophages (CD68 and
      CD163) were closely related to both miR-328 downregulation and CD44 upregulation
      in 63 patients with surgically resected gastric cancer. These findings suggest
      that macrophages in the tumor microenvironment may cause increased CD44
      expression through miR-328 suppression, resulting in tumor progression by
      enhancing ROS defense. miR-328-CD44 signaling mediated by macrophages may thus
      represent a potential target for the treatment of gastrointestinal cancer. 

PMID- 24318998
TI  - Combining evolutionary information extracted from frequency profiles with
      sequence-based kernels for protein remote homology detection.
AB  - MOTIVATION: Owing to its importance in both basic research (such as molecular
      evolution and protein attribute prediction) and practical application (such as
      timely modeling the 3D structures of proteins targeted for drug development),
      protein remote homology detection has attracted a great deal of interest. It is
      intriguing to note that the profile-based approach is promising and holds high
      potential in this regard. To further improve protein remote homology detection, a
      key step is how to find an optimal means to extract the evolutionary information
      into the profiles. RESULTS: Here, we propose a novel approach, the so-called
      profile-based protein representation, to extract the evolutionary information via
      the frequency profiles. The latter can be calculated from the multiple sequence
      alignments generated by PSI-BLAST. Three top performing sequence-based kernels
      (SVM-Ngram, SVM-pairwise and SVM-LA) were combined with the profile-based protein
      representation. Various tests were conducted on a SCOP benchmark dataset that
      contains 54 families and 23 superfamilies. The results showed that the new
      approach is promising, and can obviously improve the performance of the three
      kernels. Furthermore, our approach can also provide useful insights for studying
      the features of proteins in various families. It has not escaped our notice that
      the current approach can be easily combined with the existing sequence-based
      methods so as to improve their performance as well. AVAILABILITY AND
      IMPLEMENTATION: For users' convenience, the source code of generating the profile
      based proteins and the multiple kernel learning was also provided at
      http://bioinformatics.hitsz.edu.cn/main/~binliu/remote/

PMID- 24318999
TI  - A phylogenetic Kalman filter for ancestral trait reconstruction using molecular
      data.
AB  - MOTIVATION: Correlation between life history or ecological traits and genomic
      features such as nucleotide or amino acid composition can be used for
      reconstructing the evolutionary history of the traits of interest along
      phylogenies. Thus far, however, such ancestral reconstructions have been done
      using simple linear regression approaches that do not account for phylogenetic
      inertia. These reconstructions could instead be seen as a genuine comparative
      regression problem, such as formalized by classical generalized least-square
      comparative methods, in which the trait of interest and the molecular predictor
      are represented as correlated Brownian characters coevolving along the phylogeny.
      RESULTS: Here, a Bayesian sampler is introduced, representing an alternative and
      more efficient algorithmic solution to this comparative regression problem,
      compared with currently existing generalized least-square approaches.
      Technically, ancestral trait reconstruction based on a molecular predictor is
      shown to be formally equivalent to a phylogenetic Kalman filter problem, for
      which backward and forward recursions are developed and implemented in the
      context of a Markov chain Monte Carlo sampler. The comparative regression method
      results in more accurate reconstructions and a more faithful representation of
      uncertainty, compared with simple linear regression. Application to the
      reconstruction of the evolution of optimal growth temperature in Archaea, using
      GC composition in ribosomal RNA stems and amino acid composition of a sample of
      protein-coding genes, confirms previous findings, in particular, pointing to a
      hyperthermophilic ancestor for the kingdom. AVAILABILITY AND IMPLEMENTATION: The
      program is freely available at www.phylobayes.org.

PMID- 24319000
TI  - Chemical structure informing statistical hypothesis testing in metabolomics.
AB  - MOTIVATION: Metabolomics has been shown as an effective tool to study various
      biological and biomedical phenotypes, whereas interrogating the inherently noisy
      metabolite concentration data with limited sample size remains a major challenge.
      Accumulating evidence suggests that metabolites' structures are relevant to their
      bioactivities. RESULTS: We present a new strategy to boost the statistical power
      of hypothesis testing in metabolomics by incorporating quantitative molecular
      descriptors for each metabolite. The strategy selects potentially informative
      summary molecular descriptors and outputs chemical structure-informed false
      discovery rates. The effectiveness of the proposed strategy is demonstrated by
      both simulation studies and a real application. In a metabolomic study on
      Alzheimer's disease, the posterior inclusion probability for summary molecular
      descriptors reaches 0.97. By incorporating the structure data, our approach
      uniquely identifies multiple Alzheimer's disease signatures, which are consistent
      with existing evidence. These results evidently suggest the value of the proposed
      approach for metabolomic hypothesis-testing problems. AVAILABILITY AND
      IMPLEMENTATION: A code package implementing the strategy is freely available at
      https://github.com/HongjieZhu/CIMA.git.

PMID- 24319001
TI  - ChromoHub V2: cancer genomics.
AB  - SUMMARY: Cancer genomics data produced by next-generation sequencing support the
      notion that epigenetic mechanisms play a central role in cancer. We have
      previously developed Chromohub, an open access online interface where users can
      map chemical, structural and biological data from public repositories on
      phylogenetic trees of protein families involved in chromatin mediated-signaling.
      Here, we describe a cancer genomics interface that was recently added to
      Chromohub; the frequency of mutation, amplification and change in expression of
      chromatin factors across large cohorts of cancer patients is regularly extracted
      from The Cancer Genome Atlas and the International Cancer Genome Consortium and
      can now be mapped on phylogenetic trees of epigenetic protein families.
      Explorators of chromatin signaling can now easily navigate the cancer genomics
      landscape of writers, readers and erasers of histone marks, chromatin remodeling
      complexes, histones and their chaperones. AVAILABILITY AND IMPLEMENTATION:
      http://www.thesgc.org/chromohub/.

PMID- 24319003
TI  - Granule maturation in mast cells: histamine in control.
AB  - Mast cells are derived from committed progenitors that originate in the BM. They
      mature into histochemically distinguishable, metachromatic mast cells containing
      numerous cytoplasmic secretory granules. Accumulating evidence demonstrates that
      mast cell granule maturation is very tightly regulated by many factors including
      different granule components such as proteoglycans. In this issue of the European
      Journal of Immunology, Nakazawa et al. [Eur. J. Immunol. 2014. 44: 204-214]
      highlight a role for mast cell derived histamine as another factor critical for
      mast cell maturation. Using histidine decarboxylase (HDC) deficient mice that are
      unable to make histamine, they show poorly formed secretory granules and
      decreased secretory granule protease expression in peritoneal mast cells. Co
      culturing BM-derived mast cells with fibroblasts normally drives granule
      maturation, but HDC-deficient BM-derived mast cells fail to do so. Exogenously
      provided histamine partly restores granule differentiation as evidenced by
      increased tryptase and chymase activity, and this is histamine receptor type H4 
      dependent. However, H4 -deficient mice have intact granule formation in
      peritoneal mast cells, suggesting that when HDC is functional, the intrinsic
      histamine production is sufficient for most granule maturation processes and H4
      is dispensable. This study highlights the role of histamine in the regulation of
      mast cell maturation, although the cytosolic target remains unknown. 

PMID- 24319002
TI  - RNA-seq differential expression studies: more sequence or more replication?
AB  - MOTIVATION: RNA-seq is replacing microarrays as the primary tool for gene
      expression studies. Many RNA-seq studies have used insufficient biological
      replicates, resulting in low statistical power and inefficient use of sequencing
      resources. RESULTS: We show the explicit trade-off between more biological
      replicates and deeper sequencing in increasing power to detect differentially
      expressed (DE) genes. In the human cell line MCF7, adding more sequencing depth
      after 10 M reads gives diminishing returns on power to detect DE genes, whereas
      adding biological replicates improves power significantly regardless of
      sequencing depth. We also propose a cost-effectiveness metric for guiding the
      design of large-scale RNA-seq DE studies. Our analysis showed that sequencing
      less reads and performing more biological replication is an effective strategy to
      increase power and accuracy in large-scale differential expression RNA-seq
      studies, and provided new insights into efficient experiment design of RNA-seq
      studies. AVAILABILITY AND IMPLEMENTATION: The code used in this paper is provided
      on: http://home.uchicago.edu/~jiezhou/replication/. The expression data is
      deposited in the Gene Expression Omnibus under the accession ID GSE51403.

PMID- 24319004
TI  - Factors Influencing RNs' Perceptions of Quality Geriatric Care in Rural
      Hospitals.
AB  - The rapidly aging population and their frequent use of hospital services will
      create substantial quality challenges in the near future. Redesigning rural
      hospital work environments is the key to improving the quality of care for older
      adults. This study explored how the work environment influences registered
      nurses' (RNs') perceived quality of geriatric care in rural hospitals. We used an
      exploratory mixed-methods research design emphasizing the qualitative data (in
      depth, semi-structured interviews). Quantitative data (questionnaire) measuring
      the RN work environment were also collected to augment qualitative data. Four
      themes emerged: (a) collegial RN relationships, (b) poor staffing/utilization,
      (c) technology benefits/challenges, and (d) RN-physician interactions, which were
      identified as key factors influencing the quality of geriatric care. We concluded
      that rural hospital work environments may not be optimized to facilitate the
      delivery of quality geriatric care. Targeted interventions are needed to improve
      overall quality of care for hospitalized older adults in rural settings. 

PMID- 24319005
TI  - T-cell Ig and ITIM domain regulates natural killer cell activation in murine
      acute viral hepatitis.
AB  - Uncontrolled natural killer (NK) cell activation during the early response to
      acute viral infection can lead to severe immunopathology, and the mechanisms NK
      cells use to achieve self-tolerance in such contexts are currently unclear. Here,
      NK cells up-regulated a coinhibitory receptor, T-cell Ig and ITIM domain (TIGIT),
      during challenge with the viral double-stranded RNA (dsRNA) analog poly I:C.
      Blocking TIGIT by antibody treatment in vivo or a genetic deficiency in Tigit
      enhanced NK cell activation and aggravated liver injury in a poly I:C/D-GalN
      induced model of acute fulminant hepatitis, suggesting that TIGIT is normally
      required for protecting against NK cell-mediated liver injury. Furthermore,
      adoptively transferring Tigit(-/-) NK cells into NK cell-deficient Nfil3(-/-)
      mice also resulted in elevated liver injury. Reconstituting Kupffer cell-depleted
      mice with poliovirus receptor (PVR/CD155, a TIGIT ligand)-silenced Kupffer cells
      led to aggravated liver injury in a TIGIT-dependent manner. Blocking TIGIT in an
      NK-Kupffer cell coculture in vitro enhanced NK cell activation and interferon
      gamma (IFN-gamma) production in a PVR-dependent manner. We also found that TIGIT
      was up-regulated selectively on NK cells and protected against liver injury in an
      acute adenovirus infection model in both an NK cell- and Kupffer cell-dependent
      manner. Knocking down PVR in Kupffer cells resulted in aggravated liver injury in
      response to adenovirus infection in a TIGIT-dependent manner. CONCLUSION: TIGIT
      negatively regulates NK-Kupffer cell crosstalk and alleviates liver injury in
      response to poly I:C/D-GalN challenge or acute adenovirus infection, suggesting a
      novel mechanism of NK cell self-tolerance in liver homeostasis during acute viral
      infection.

PMID- 24319006
TI  - Novel LEPR mutations in obese Pakistani children identified by PCR-based
      enrichment and next generation sequencing.
AB  - OBJECTIVE: Mutations in leptin receptor gene (LEPR) result in early onset extreme
      adiposity. However, their prevalence in different populations is not known.
      Indeed, LEPR screening by gold standard Sanger sequencing has been limited by its
      large size and the cost. One-step PCR-based targeted enrichment could be an
      option for rapid and cost effective molecular diagnosis of monogenic forms of
      obesity. METHODS: The study is based on 39 unrelated severely obese Pakistani
      children, previously shown to be negative for leptin (LEP) and melanocortin 4
      receptor (MC4R) gene mutations, from an initial cohort of 62 probands. Patient
      samples were analyzed by microdroplet PCR-enrichment (RainDance technologies)
      targeting coding exons of 26 obesity-associated genes combined with next
      generation sequencing. Hormone levels were analyzed by ELISA. RESULTS: The
      analysis revealed two novel homozygous LEPR mutations, an essential splice site
      mutation in exon 15 (c.2396-1 G>T), and a nonsense mutation in exon 10 (c.1675
      G>A). Both probands had high leptin levels and were phenotypically
      indistinguishable from age-matched leptin-deficient subjects from the same
      population. CONCLUSIONS: The two subjects carrying homozygous LEPR mutations,
      reported here for the first time in the Pakistani population, constitute 3% of
      the whole cohort of severely obese children (compared to 17% for LEP and 3% for
      MC4R).

PMID- 24319007
TI  - A recent review of non-biological remediation of aflatoxin-contaminated crops.
AB  - Aflatoxins are highly toxic, mutagenic, teratogenic and carcinogenic compounds
      produced predominantly as secondary metabolites by certain species of fungi
      belonging to the Aspergillus genus. Owing to the significant health risks and
      economic impacts associated with the presence of aflatoxins in agricultural
      commodities, a considerable amount of research has been directed at finding
      methods to prevent toxicity. This review compiles the recent literature of
      methods for the detoxification and management of aflatoxin in post-harvest
      agricultural crops using non-biological remediation.

PMID- 24319008
TI  - Using systems approaches to address challenges for clinical implementation of
      pharmacogenomics.
AB  - Many genetic variants have been shown to affect drug response through changes in
      drug efficacy and likelihood of adverse effects. Much of pharmacogenomic science
      has focused on discovering and clinically implementing single gene variants with
      large effect sizes. Given the increasing complexities of drug responses and their
      variability, a systems approach may be enabling for discovery of new biology in
      this area. Further, systems approaches may be useful in addressing challenges in
      moving these data to clinical implementation, including creation of predictive
      models of drug response phenotypes, improved clinical decision-making through
      complex biological models, improving strategies for integrating genomics into
      clinical practice, and evaluating the impact of implementation programs on public
      health.

PMID- 24319009
TI  - Simultaneous integrated boost to intraprostatic lesions using different energy
      levels of intensity-modulated radiotherapy and volumetric-arc therapy.
AB  - OBJECTIVE: This study compared the dosimetry of volumetric-arc therapy (VMAT) and
      intensity-modulated radiotherapy (IMRT) with a dynamic multileaf collimator using
      the Monte Carlo algorithm in the treatment of prostate cancer with and without
      simultaneous integrated boost (SIB) at different energy levels. METHODS: The data
      of 15 biopsy-proven prostate cancer patients were evaluated. The prescribed dose
      was 78 Gy to the planning target volume (PTV78) including the prostate and
      seminal vesicles and 86 Gy (PTV86) in 39 fractions to the intraprostatic lesion,
      which was delineated by MRI or MR-spectroscopy. RESULTS: PTV dose homogeneity was
      better for IMRT than VMAT at all energy levels for both PTV78 and PTV86. Lower
      rectum doses (V30-V50) were significantly higher with SIB compared with PTV78
      plans in both IMRT and VMAT plans at all energy levels. The bladder doses at high
      dose level (V60-V80) were significantly higher in IMRT plans with SIB at all
      energy levels compared with PTV78 plans, but no significant difference was
      observed in VMAT plans. VMAT plans resulted in a significant decrease in the mean
      monitor units (MUs) for 6, 10, and 15 MV energy levels both in plans with and
      those without SIB. CONCLUSION: Dose escalation to intraprostatic lesions with 86
      Gy is safe without causing serious increase in organs at risk (OARs) doses. VMAT
      is advantageous in sparing OARs and requiring less MU than IMRT. ADVANCES IN
      KNOWLEDGE: VMAT with SIB to intraprostatic lesion is a feasible method in
      treating prostate cancer. Additionally, no dosimetric advantage of higher energy
      is observed.

PMID- 24319010
TI  - Engineered skeletal muscle tissue for soft robotics: fabrication strategies,
      current applications, and future challenges.
AB  - Skeletal muscle is a scalable actuator system used throughout nature from the
      millimeter to meter length scales and over a wide range of frequencies and force
      regimes. This adaptability has spurred interest in using engineered skeletal
      muscle to power soft robotics devices and in biotechnology and medical
      applications. However, the challenges to doing this are similar to those facing
      the tissue engineering and regenerative medicine fields; specifically, how do we
      translate our understanding of myogenesis in vivo to the engineering of muscle
      constructs in vitro to achieve functional integration with devices. To do this
      researchers are developing a number of ways to engineer the cellular
      microenvironment to guide skeletal muscle tissue formation. This includes
      understanding the role of substrate stiffness and the mechanical environment,
      engineering the spatial organization of biochemical and physical cues to guide
      muscle alignment, and developing bioreactors for mechanical and electrical
      conditioning. Examples of engineered skeletal muscle that can potentially be used
      in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D
      skeletal muscle tissues engineered using scaffolds or directed self-organization.
      Integration into devices has led to basic muscle-powered devices such as grippers
      and pumps as well as more sophisticated muscle-powered soft robots that walk and
      swim. Looking forward, current, and future challenges include identifying the
      best source of muscle precursor cells to expand and differentiate into myotubes,
      replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of
      choice for soft robots, and vascularization and innervation to enable control and
      nourishment of larger muscle tissue constructs.

PMID- 24319011
TI  - Roles of rpoS-activating small RNAs in pathways leading to acid resistance of
      Escherichia coli.
AB  - Escherichia coli and related enteric bacteria can survive under extreme acid
      stress condition at least for several hours. RpoS is a key factor for acid stress
      management in many enterobacteria. Although three rpoS-activating sRNAs, DsrA,
      RprA, and ArcZ, have been identified in E. coli, it remains unclear how these
      small RNA molecules participate in pathways leading to acid resistance (AR).
      Here, we showed that overexpression of ArcZ, DsrA, or RprA enhances AR in a RpoS
      dependent manner. Mutant strains with deletion of any of three sRNA genes showed
      lowered AR, and deleting all three sRNA genes led to more severe defects in
      protecting against acid stress. Overexpression of any of the three sRNAs fully
      rescued the acid tolerance defects of the mutant strain lacking all three genes,
      suggesting that all three sRNAs perform the same function in activating RpoS
      required for AR. Notably, acid stress led to the induction of DsrA and RprA but
      not ArcZ. 

PMID- 24319012
TI  - A novel autoantibody against moesin in the serum of patients with MPO-ANCA
      associated vasculitis.
AB  - BACKGROUND: Antineutrophil cytoplasmic autoantibody (ANCA) directed against
      myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis
      (MPO-AAV), does not always correlate with disease activity. Here, we detected
      autoantibodies against moesin, which was located on the surface of stimulated
      endothelial cells, in the serum of patients. METHODS: The anti-moesin
      autoantibody titer was evaluated by ELISA. Seventeen kinds of
      cytokines/chemokines were measured by a Bio-Plex system. RESULTS: Serum
      creatinine in the anti-moesin autoantibody-positive group was higher than that in
      the negative group. Additionally, interferon (IFN)-gamma, macrophage chemotactic
      peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13,
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony
      stimulating factor were significantly higher in the positive group. Furthermore,
      IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer.
      Based on these findings and the binding of anti-moesin IgG to neutrophils and
      monocytes, we detected the secretion of cytokines/chemokines such as IFN-gamma,
      MCP-1 and GM-CSF from these cells. CONCLUSIONS: The anti-moesin autoantibody
      existed in the serum of patients with MPO-AAV and was associated with the
      production of inflammatory cytokines/chemokines targeting neutrophils with a
      cytoplasmic profile, which suggests that the anti-moesin autoantibody has the
      possibility to be a novel autoantibody developing vasculitis via neutrophil and
      endothelial cell activation.

PMID- 24319013
TI  - Intravenous iron therapy in non-dialysis CKD patients.

PMID- 24319014
TI  - Proteinuric effect of transcranial magnetic stimulation in healthy subjects and
      diabetic patients with stage 3-4 CKD.
AB  - BACKGROUND: Many authors have investigated the numerous connections between the
      nervous system and kidneys, and recent literature has indicated that these
      similar systems are interconnected. Recent scientific works have shown that there
      is similarity between the cerebral cortex 'viscera representation' and the 'motor
      omunculus'. We studied the connection between the brain and kidney in vivo using
      repetitive transcranial magnetic stimulation (rTMS). Proteinuria and albuminuria
      were used as markers of renal response in patients with diabetes (DP) and in a
      group of healthy subjects (HSs) who received rTMS for 5 consecutive days.
      METHODS: The study population consists of the following four groups: Group A (HS
      stimulated), Group B (HS sham), Group C (DP stimulated) and Group D (DP sham).
      All subjects in Groups A and C underwent rTMS delivered at a frequency
      corresponding to 90% of the threshold at rest for 5 consecutive days. All
      subjects in Groups B and D underwent rTMS delivered with the coil placed on the
      scalp without delivering electromagnetic stimuli, while another coil at a
      distance of ~2 m emitted stimuli at a very low intensity. This strategy ensured
      that brain stimulation would not occur, so that the subjects felt the vibrations
      produced by the click of the TMS coil. The proteinuria and albuminuria of 24 h
      and creatinine clearance were measured at time 0 (T0), after the first session
      (T1), at the end of the treatment (T5) and 24 h after the last stimulation (Post
      24 h). RESULTS: In Group A, there was a statistically significant increase in
      albuminuria (5.65 +/- 0.52 versus 12 +/- 0.55 mg/24 h, P = 0.0001) and
      proteinuria (6.05 +/- 0.48 versus 13.1 +/- 0.60 mg/24 h, P = 0.0001) at the end
      of the treatment (T5) compared with the baseline values (T0). In Group C, the
      albuminuria was statistically higher at T5 than the baseline T0 (416.22 +/- 181
      versus 677.25 +/- 280 mg/24 h, P = 0.04), as was proteinuria (561.37 +/- 86
      versus 865.125 +/- 104 mg/24 h, P = 0.0001); in Group C, the increase in
      albuminuria (T0 versus post 24 h, P = 0.02) and proteinuria (T0 versus 24 h post,
      P = 0.0002) persisted at 24 h post. In Groups B and D, statistically significant
      changes were not found in proteinuria (Group B T0 versus T5, P = 0.61; Group D:
      T0 versus T5, P = 0.66) and albuminuria (Group B T0 versus T5, P = 0.15; Group D
      T0 versus T5, P = 0.44) measured at the same times. CONCLUSIONS: Consecutive rTMS
      is able to induce a statistically significant increase in albuminuria and
      proteinuria in HS and DP. A functional link between the brain and kidney is
      possible. For the first time, the results have indicated an increase of
      proteinuria in subjects undergoing transcranial stimulation.

PMID- 24319015
TI  - The authors reply.

PMID- 24319016
TI  - Cathepsin S contributes to macrophage migration via degradation of elastic fibre
      integrity to facilitate vein graft neointimal hyperplasia.
AB  - AIMS: Cathepsin S (Cat S) is a potent lysosomal protease that is secreted into
      the extracellular space and has been implicated in elastin and collagen
      degradation in diseases such as atherosclerosis. Elastin degradation plays an
      important role in vascular remodelling. However, the mechanism by which Cat
      regulates this process and its contribution to vein graft remodelling remains
      unclear. METHODS AND RESULTS: Using a murine vein graft model, we examined the
      expression pattern of Cat family members. Expression of cathepsin genes was
      induced in vein grafts, with that of Cat S being the highest. Elevated Cat S
      expression was confirmed in both mouse and human vein grafts. To explore the role
      of Cat S, vein grafts were created between wild-type (WT) littermates and Cat S
      knockout (Cat S KO) mice. Knockout of Cat S in the recipients (vein(CatS-KO)
      artery(CatS-KO) or vein(WT)-artery(CatS-KO)) significantly inhibited neointima
      formation and reduced the accumulation of macrophages and proliferation of smooth
      muscle cells in vein grafts. Knockout of Cat S preserved the elastic fibre
      integrity of vein grafts and inhibited the migration of macrophages across the
      elastin fibres. CONCLUSION: These results demonstrated that Cat S contributes to
      macrophage migration via degradation of elastic fibre integrity to facilitate
      neointima formation of vein grafts, which might provide a novel therapeutic
      target for preserving vein graft patency.

PMID- 24319017
TI  - Reducing lung cancer and other tobacco-related cancers in Europe: smoking
      cessation is the key.

PMID- 24319018
TI  - Prediction of postchemotherapy ovarian function using markers of ovarian reserve.
AB  - BACKGROUND: Reproductive-aged women frequently receive both chemotherapy and
      endocrine therapy as part of their treatment regimen for early stage hormone
      receptor-positive breast cancer. Chemotherapy results in transient or permanent
      ovarian failure in the majority of women. The difficulty in determining which
      patients will recover ovarian function has implications for adjuvant endocrine
      therapy decision making. We hypothesized that pretreatment serum anti-Mullerian
      hormone (AMH) and inhibin B concentrations would predict for ovarian function
      following chemotherapy. METHODS: Pre- and perimenopausal women aged 25-50 years
      with newly diagnosed breast cancer were enrolled. Subjects underwent phlebotomy
      for assessment of serum AMH, inhibin B, follicle-stimulating hormone, and
      estradiol prior to chemotherapy and 1 month and 1 year following completion of
      treatment. Associations among hormone concentrations, clinical factors, and
      biochemically assessed ovarian function were assessed. RESULTS: Twenty-seven
      subjects were evaluable for the primary endpoint. Median age was 41. Twenty
      subjects (74.1%) experienced recovery of ovarian function within 18 months. Of
      the 26 evaluable subjects assessed prior to chemotherapy, 19 (73.1%) had
      detectable serum concentrations of AMH. The positive predictive value of a
      detectable baseline serum AMH concentration for recovery of ovarian function was
      94.7%, and the negative predictive value was 85.7%. On univariate analysis,
      younger age and detectable serum AMH concentration at chemotherapy initiation
      were predictive of increased likelihood of recovery of ovarian function.
      CONCLUSION: Prechemotherapy assessment of serum AMH may be useful for predicting
      postchemotherapy ovarian function. This finding has implications for decision
      making about adjuvant endocrine therapy in premenopausal women treated with
      chemotherapy.

PMID- 24319019
TI  - New oral anticoagulants and the cancer patient.
AB  - Indications for anticoagulation are common in patients with malignancy. Cancer
      patients have an increased risk of developing venous thromboembolic events or may
      have other indications for anticoagulation, such as atrial fibrillation. New oral
      anticoagulants (NOACs) are now available that offer increased options for
      anticoagulation beyond the traditional vitamin K antagonists and low molecular
      weight heparins that have long been the cornerstone of treatment. This review
      will focus on the three NOACs that are currently approved for use in the U.S.:
      the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors, apixaban
      and rivaroxaban. Oncologists are likely to encounter an increasing number of
      patients taking these agents at the time of their cancer diagnosis or to have
      patients who develop indications for anticoagulation during the course of their
      disease. The basic pharmacology, current clinical indications, and approach to
      the use of NOACs in the cancer patient will be reviewed. 

PMID- 24319021
TI  - Seizure control for intracranial arteriovenous malformations is directly related
      to treatment modality: a meta-analysis.
AB  - OBJECT: Seizures are a common presenting sign of intracranial arteriovenous
      malformations (AVMs). The object of this meta-analysis was to determine if the
      modality selected to treat AVMs affects the rate of seizure outcomes. METHODS:
      All published data describing seizure status as an outcome goal over the past 20
      years were included in this study. Seizure outcomes following microsurgery (MS),
      endovascular embolization for cure (EVE), or stereotactic radiosurgery (SRS) were
      compared using a validated random effect logistic regression approach. RESULTS:
      24 studies, with a total of 1157 patients, were analyzed. Overall, the
      microsurgical group had the best seizure control (p<0.01), with the relative
      predicted rates of seizure outcome as follows: MS 78.3% (95% CI 70.1% to 85.8%);
      SRS 62.8% (95% CI 55.0% to 70.0%); and EVE 49.3% (95% CI 32.1% to 66.6%).
      Patients in the SRS group who had complete obliteration of their AVMs achieved
      the highest rate of seizure control (85.2% (95% CI 79.1% to 91.2%); p<0.01). The
      development of new onset seizures occurred more frequently in patients undergoing
      EVE (39.4% (95% CI 8.1% to 67.8%)) compared with MS (9.1% (95% CI 5.0% to 13.1%))
      and SRS (5.4% (95% CI 3.0% to 7.8%)) (p<0.3 and p<0.01, respectively).
      CONCLUSIONS: This is the first meta-analysis designed to study relative rates of
      seizure outcomes following the currently utilized AVM treatment modalities. In
      general, MS results in the highest proportion of seizure control. However, if SRS
      results in successful obliteration of the AVM, then this modality is the most
      effective in achieving seizure control.

PMID- 24319020
TI  - Zollinger-Ellison syndrome: classical considerations and current controversies.
AB  - Zollinger-Ellison syndrome (ZES) is an endocrinopathy characterized by gastrin
      secreting tumors, responsible for causing the formation of multiple, refractory,
      and recurrent peptic ulcers in the distal duodenum and proximal jejunum. Two main
      variants have been described, sporadic and those found in association with
      parathyroid and pituitary tumors, a genetic disorder known as multiple endocrine
      neoplasia-1 (MEN-1). Biochemical serum evaluation for elevated gastrin, followed
      by radiological or nuclear localization of the primary lesion, is mandated for
      establishing diagnosis. The mainstays of treatment include management of
      hypersecretory state with medical suppression of gastric acid production and
      surgical resection of primary tumor for the prevention of malignant
      transformation and metastatic complications. Medical therapy with proton pump
      inhibitors has virtually eliminated the need for acid-reducing surgical
      procedures. Surgical approach to sporadic and MEN-1-associated ZES varies based
      on our understanding of the natural history of the condition and the probability
      of cure; however, resection to a negative microscopic margin is indicated in both
      cases. Postoperative surveillance involves measurement of gastrin level, followed
      by imaging if elevation is detected. Re-excision of recurrent or resection of
      metastatic disease is a subject of controversy; however, at the present time
      aggressive cytoreductive approach is favored. 

PMID- 24319022
TI  - AVM Management Equipoise Survey: physician opinions regarding the management of
      brain arteriovenous malformations.
AB  - INTRODUCTION: Management of unruptured brain arteriovenous malformations (AVMs)
      is controversial, and conducting clinical trials in this area has been a
      challenge. We sought to determine which, if any, patient/AVM characteristics were
      most likely to influence clinicians' decisions regarding management and clinical
      trial enrollment. METHODS: We performed an online survey (Survey Monkey) of
      members of the American Association of Neurological Surgeons (AANS) (n=4836) and
      Society of NeuroInterventional Surgeons (SNIS) (n=512). Physicians were asked to
      rate the likelihood that various patient/AVM characteristics would influence
      their treatment decisions and recommendations for clinical trial enrollment. 10
      hypothetical case vignettes were also provided, and respondents were asked to
      select a management recommendation. RESULTS: 277 (5.2%) responses were received.
      Characteristics that the majority (>50%) of respondents felt should lead to
      treatment included size <3 cm, superficial or cerebellar location, single
      draining vein, age <30 years, venous aneurysm, prior AVM hemorrhage, poorly
      controlled seizures, intranidal aneurysm, and patient's desire for treatment.
      However, a significant minority (>30%) felt that six of these same
      characteristics should lead to observation or should not influence treatment
      decisions. Characteristics that the majority (>50%) of respondents felt should
      lead to clinical trial enrollment included size > 6 cm, deep or eloquent
      location, and age 51-70 years. The only characteristic that the majority felt
      should not lead to enrollment was the presence of an intranidal aneurysm. For the
      10 vignettes, the majority of respondents (>50%) favored a specific course of
      management in only five cases. CONCLUSIONS: Clinicians' opinions on which
      patient/AVM characteristics are important for decisions regarding treatment or
      trial enrollment vary widely. These results suggest that there is no uniform
      opinion of clinical equipoise with regard to the management of brain AVMs.

PMID- 24319023
TI  - Letter to the glycoforum transforming glycoscience: an Australian perspective.

PMID- 24319025
TI  - Flow diverter assisted coil embolization of a very small ruptured ophthalmic
      artery aneurysm.
AB  - Small ruptured aneurysms present a unique problem to endovascular therapy. We
      report a case in which a patient presented with subarachnoid hemorrhage and a
      very small ruptured ophthalmic artery aneurysm, for which endovascular therapy
      was preferred secondary to severe cardiac comorbidities. Due to the aneurysm
      size, a small 1.5 mm coil was needed, but presented a significant risk of
      migration. Conventional stent assisted coiling was considered suboptimal as the
      small coil could have easily migrated through the strut. We present a novel
      technique of flow diverter assisted coil embolization in which a coil was placed
      within the aneurysm and a pipeline embolization device was then partially
      deployed, jailing the microcatheter and coil mass. Once in place, the coil was
      detached, securing the aneurysm, and preventing coil migration. Through the use
      of a flow diverter, some degree of aneurysm protection would still be expected in
      the event of coil migration toward the ophthalmic artery origin. 

PMID- 24319026
TI  - Intrathoracic schwannoma with Horner syndrome.
AB  - Horner syndrome (HS) results from the interruption of the sympathetic pathway to
      the eye and face, and describes a collection of signs consisting of ipsilateral
      miosis, partial ptosis, anhidrosis and apparent enophthalmos. It is a clinical
      observation, and has a plethora of possible causes, ranging from the benign to
      the malignant. Involvement of the stellate ganglion on the sympathetic chain by
      malignant tumours of the lung is a well-recognised cause of HS. On the other
      hand, HS secondary to the excessive growth of a benign intrathoracic neoplasm is
      a very rare finding, with only a few cases described in the literature. Our
      patient was found to have such a diagnosis when he presented to medical attention
      with a 1-month history of cough that was associated with features of HS that he
      had ignored for the preceding 9 years. 

PMID- 24319027
TI  - Does citrus leaf miner impair hydraulics and fitness of citrus host plants?
AB  - Gas exchange and hydraulic features were measured in leaves of three different
      Citrus species (Citrus aurantium L., Citrus limon L., Citrus  *  paradisii
      Macfad) infested by Phyllocnistis citrella Staiton, with the aim to quantify the
      impact of this pest on leaf hydraulics and, ultimately, on plant fitness.
      Infested leaves were characterized by the presence on the leaf blade of typical
      snake-shaped mines and, in some cases, of a crumpled leaf blade. Light microscopy
      showed that leaf crumpling was induced by damage to the cuticular layer. In all
      three Citrus species examined: (a) the degree of infestation did not exceed 10%
      of the total surface area of infested plants; (b) control and infested leaves
      showed similar values of minimum diurnal leaf water potential, leaf hydraulic
      conductance and functional vein density; and (c) maximum diurnal values of
      stomatal conductance to water vapour, transpiration rate and photosynthetic rate
      (An) were similar in both control leaves and the green areas of infested leaves.
      A strong reduction of An was recorded only in mined leaf areas. Our data suggest
      that infestation with P. citrella does not cause conspicuous plant productivity
      reductions in young Citrus plants, at least not in the three Citrus species
      studied here. 

PMID- 24319028
TI  - Hydraulics of high-yield orchard trees: a case study of three Malus domestica
      cultivars.
AB  - The drought tolerance of three economically important apple cultivars, Golden
      Delicious, Braeburn and Red Delicious, was analysed. The work offers insights
      into the hydraulics of these high-yield trees and indicates a possible hydraulic
      limitation of carbon gain. The hydraulic safety and efficiency of branch xylem
      and leaves were quantified, drought tolerance of living tissues was measured and
      stomatal regulation, turgor-loss point and osmotic potential at full turgor were
      analysed. Physiological measurements were correlated with anatomical parameters,
      such as conduit diameter, cell-wall reinforcement, stomatal density and stomatal
      pore length. Hydraulic safety differed considerably between the three cultivars
      with Golden Delicious being significantly less vulnerable to drought-induced
      embolism than Braeburn and Red Delicious. In Golden Delicious, leaves were less
      resistant than branch xylem, while in the other cultivars leaves were more
      resistant than branch xylem. Hydraulic efficiency and xylem anatomical
      measurements indicate differences in pit properties, which may also be
      responsible for variations in hydraulic safety. In all three cultivars, full
      stomatal closure occurred at water potentials where turgor had already been lost
      and severe loss of hydraulic conductivity as well as damage to living cells had
      been induced. The consequential negative safety margins pose a risk for hydraulic
      failure but facilitate carbon gain, which is further improved by the observed
      high stomatal conductance. Maximal stomatal conductance was clearly seen to be
      related to stomatal density and size. Based on our results, these three high
      yield Malus domestica Borkh. cultivars span a wide range of drought tolerances,
      appear optimized for maximal carbon gain and, thus, all perform best under well
      managed growing conditions. 

PMID- 24319030
TI  - Contrasting water strategies of two Mediterranean shrubs of limited distribution:
      uncertain future under a drier climate.
AB  - Plants have evolved different strategies to cope with drought, involving
      alternative ecophysiologies and different levels of plasticity. These strategies
      are critical for species of limited distribution, which are especially vulnerable
      to the current rates of rapid environmental change. The aim of this study was to
      assess the water strategy of two species with limited distribution, Cneorum
      tricoccon L. and Rhamnus ludovici-salvatoris Chodat., and evaluate their
      interpopulation variability along an aridity gradient to estimate their
      vulnerability to a drier climate. We measured different ecophysiological traits
      influenced by drought--stomatal conductance, maximum photochemical efficiency of
      photosynthesis II, carbon isotope ratio and chlorophyll concentration--in two
      climatically contrasting years, before and during summer drought. Both species
      were vulnerable to drought at the aridity limit of the gradient, but showed
      contrasting water strategies: while C. tricoccon was consistent in its water
      conservation strategy across the aridity gradient, R. ludovici-salvatoris was
      not, displaying higher and more variable stomatal conductances and being able to
      increase water-use efficiency at the most xeric sites. Changes in length and
      intensity of drought events may favor one species' strategy to the detriment of
      the other: C. tricoccon is more vulnerable to chronic and prolonged droughts,
      whereas short but acute droughts might have a stronger effect on R. ludovici
      salvatoris. In those communities where these two species coexist, such different
      strategies might lead to changes in community structure under climate change
      scenarios, with unknown cascade effects on ecosystem functioning.

PMID- 24319031
TI  - Plagiarism and journal ethics.

PMID- 24319032
TI  - Comment on "multimodal analgesia therapy reduces length of hospitalization in
      patients undergoing fusions of the ankle and hindfoot".

PMID- 24319033
TI  - Author response.

PMID- 24319034
TI  - AO and Lauge-Hansen classification systems for ankle fractures.

PMID- 24319035
TI  - Author response.

PMID- 24319037
TI  - International electives in neurology training: a survey of US and Canadian
      program directors.
AB  - OBJECTIVE: To ascertain the current status of global health training and
      humanitarian relief opportunities in US and Canadian postgraduate neurology
      programs. BACKGROUND: There is a growing interest among North American trainees
      to pursue medical electives in low- and middle-income countries. Such training
      opportunities provide many educational and humanitarian benefits but also pose
      several challenges related to organization, human resources, funding, and trainee
      and patient safety. The current support and engagement of neurology postgraduate
      training programs for trainees to pursue international rotations is unknown.
      METHODS: A survey was distributed to all program directors in the United States
      and Canada (December 2012-February 2013) through the American Academy of
      Neurology to assess the training opportunities, institutional partnerships, and
      support available for international neurology electives. RESULTS: Approximately
      half of responding programs (53%) allow residents to pursue global health-related
      electives, and 11% reported that at least 1 trainee participated in humanitarian
      relief during training (survey response rate 61%, 143/234 program directors).
      Canadian programs were more likely to allow residents to pursue international
      electives than US programs (10/11, 91% vs 65/129, 50%, p = 0.023). The number of
      trainees participating in international electives was low: 0%-9% of residents
      (55% of programs) and 10%-19% of residents (21% of programs). Lack of funding was
      the most commonly cited reason for residents not participating in global health
      electives. If funding was available, 93% of program directors stated there would
      be time for residents to participate. Most program directors (75%) were
      interested in further information on global health electives. CONCLUSIONS: In
      spite of high perceived interest, only half of US neurology training programs
      include international electives, mostly due to a reported lack of funding. By
      contrast, the majority of Canadian programs that responded allow international
      electives, likely due to clearer guidelines from the Royal College of Physicians
      and Surgeons of Canada compared to the Accreditation Council of Graduate Medical
      Education. However, the number of both Canadian and US neurology trainees
      venturing abroad remains a minority. Most program directors are interested in
      learning more information related to global health electives for neurology
      residents.

PMID- 24319029
TI  - Influence of water deficit on the molecular responses of Pinus contorta * Pinus
      banksiana mature trees to infection by the mountain pine beetle fungal associate,
      Grosmannia clavigera.
AB  - Conifers exhibit a number of constitutive and induced mechanisms to defend
      against attack by pests and pathogens such as mountain pine beetle (Dendroctonus
      ponderosae Hopkins) and their fungal associates. Ecological studies have
      demonstrated that stressed trees are more susceptible to attack by mountain pine
      beetle than their healthy counterparts. In this study, we tested the hypothesis
      that water deficit affects constitutive and induced responses of mature lodgepole
      pine * jack pine hybrids (Pinus contorta Dougl. ex Loud. var. latifolia Engelm.
      ex S. Wats. * Pinus banksiana Lamb.) to inoculation with the mountain pine beetle
      fungal associate Grosmannia clavigera (Robinson-Jeffrey and Davidson) Zipfel, de
      Beer and Wingfield. The degree of stress induced by the imposed water-deficit
      treatment was sufficient to reduce photosynthesis. Grosmannia clavigera-induced
      lesions exhibited significantly reduced dimensions in water-deficit trees
      relative to well-watered trees at 5 weeks after inoculation. Treatment-associated
      cellular-level changes in secondary phloem were also observed. Quantitative RT
      PCR was used to analyze transcript abundance profiles of 18 genes belonging to
      four families classically associated with biotic and abiotic stress responses:
      aquaporins (AQPs), dehydration-responsive element binding (DREB), terpene
      synthases (TPSs) and chitinases (CHIs). Transcript abundance profiles of a TIP2
      AQP and a TINY-like DREB decreased significantly in fungus-inoculated trees, but
      not in response to water deficit. One TPS, Pcb(+)-3-carene synthase, and the
      Class II CHIs PcbCHI2.1 and PcbCHI2.2 showed increased expression under water
      deficit conditions in the absence of fungal inoculation, while another TPS,
      Pcb(E)-beta-farnesene synthase-like, and two CHIs, PcbCHI1.1 and PcbCHI4.1,
      showed attenuated expression under water-deficit conditions in the presence of
      fungal inoculation. The effects were observed both locally and systemically.
      These results demonstrate that both constitutive and induced carbon- and nitrogen
      based defenses are affected by water deficit, suggesting potential consequences
      for mountain pine beetle dynamics, particularly in novel environments. 

PMID- 24319038
TI  - Motor cortex stimulation does not improve dystonia secondary to a focal basal
      ganglia lesion.
AB  - OBJECTIVE: To assess the efficacy of epidural motor cortex stimulation (MCS) on
      dystonia, spasticity, pain, and quality of life in patients with dystonia
      secondary to a focal basal ganglia (BG) lesion. METHODS: In this double-blind,
      crossover, multicenter study, 5 patients with dystonia secondary to a focal BG
      lesion were included. Two quadripolar leads were implanted epidurally over the
      primary motor (M1) and premotor cortices, contralateral to the most dystonic
      side. The leads were placed parallel to the central sulcus. Only the posterior
      lead over M1 was activated in this study. The most lateral or medial contact of
      the lead (depending on whether the dystonia predominated in the upper or lower
      limb) was selected as the anode, and the other 3 as cathodes. One month
      postoperatively, patients were randomly assigned to on- or off-stimulation for 3
      months each, with a 1-month washout between the 2 conditions. Voltage, frequency,
      and pulse width were fixed at 3.8 V, 40 Hz, and 60 MUs, respectively. Evaluations
      of dystonia (Burke-Fahn-Marsden Scale), spasticity (Ashworth score), pain
      intensity (visual analog scale), and quality of life (36-Item Short Form Health
      Survey) were performed before surgery and after each period of stimulation.
      RESULTS: Burke-Fahn-Marsden Scale, Ashworth score, pain intensity, and quality of
      life were not statistically significantly modified by MCS. CONCLUSIONS: Bipolar
      epidural MCS failed to improve any clinical feature in dystonia secondary to a
      focal BG lesion. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence
      that bipolar epidural MCS with the anode placed over the motor representation of
      the most affected limb failed to improve any clinical feature in dystonia
      secondary to a focal BG lesion.

PMID- 24319039
TI  - Anesthetic drugs in status epilepticus: risk or rescue? A 6-year cohort study.
AB  - OBJECTIVE: To evaluate the risks of continuously administered IV anesthetic drugs
      (IVADs) on the outcome of adult patients with status epilepticus (SE). METHODS:
      All intensive care unit patients with SE from 2005 to 2011 at a tertiary academic
      medical care center were included. Relative risks were calculated for the primary
      outcome measures of seizure control, Glasgow Outcome Scale score at discharge,
      and death. Poisson regression models were used to control for possible
      confounders and to assess effect modification. RESULTS: Of 171 patients, 37% were
      treated with IVADs. Mortality was 18%. Patients with anesthetic drugs had more
      infections during SE (43% vs 11%; p < 0.0001) and a 2.9-fold relative risk for
      death (2.88; 95% confidence interval 1.45-5.73), independent of possible
      confounders (i.e., duration and severity of SE, nonanesthetic third-line
      antiepileptic drugs, and critical medical conditions) and without significant
      effect modification by different grades of SE severity and etiologies. As IVADs
      were used after first- and second-line drugs failed, there was a correlation
      between treatment-refractory SE and the use of IVADs, leading to insignificant
      results regarding the risk of IVADs and outcome after additional adjustment for
      refractory SE. CONCLUSION: Our findings heighten awareness regarding adverse
      effects of IVADs. Randomized controlled trials are needed to further clarify the
      association of IVADs with outcome in patients with SE. CLASSIFICATION OF
      EVIDENCE: This study provides Class III evidence that patients with SE receiving
      IVADs have a higher proportion of infection and an increased risk of death as
      compared to patients not receiving IVADs.

PMID- 24319040
TI  - Anti-neutral glycolipid antibodies in encephalomyeloradiculoneuropathy.
AB  - OBJECTIVE: The aim of this study was to review 4 patients with
      encephalomyeloradiculoneuropathy (EMRN) and assess for autoantibodies against
      neutral glycolipids. METHODS: We studied the progression of clinical, radiologic,
      neurophysiologic, and CSF findings, as well as anti-neutral glycolipid antibodies
      in sera. RESULTS: All patients developed acute or subacute motor weakness and
      impaired consciousness. Their CSF showed pleocytosis and high immunoglobulin G
      concentrations. MRI revealed lesions in the brain and spinal cord.
      Neurophysiologic examinations indicated dysfunction of the spinal cord, nerve
      roots, and peripheral nerves. Steroid pulsed immunotherapy and/or high dose of IV
      immunoglobulin replacement therapy resulted in clear and often dramatic clinical
      improvements. Reactivity to anti-neutral glycolipid antibodies was positive in
      all patients with acute EMRN but not in the recovery phase. Forty-seven age
      matched patients with other neurologic disorders and 28 age-matched healthy
      volunteers tested negative for reactivity to anti-neutral glycolipid antibodies.
      CONCLUSION: The resolution of radiologic and neurologic abnormalities and altered
      autoantibody titers against neutral glycolipids after immunotherapy suggest that
      EMRN is caused by an immune-mediated mechanism. These autoantibodies may be
      useful biomarkers for EMRN.

PMID- 24319041
TI  - The globalization of US and Canadian neurology residency training: is it just
      about the money?

PMID- 24319042
TI  - Left atrial appendage occlusion in atrial fibrillation after intracranial
      hemorrhage.
AB  - OBJECTIVE: To evaluate the safety and feasibility of percutaneous left atrial
      appendage occlusion (LAAO) in patients with atrial fibrillation (AF) and previous
      intracranial hemorrhage (ICH). METHODS: In an explorative, prospective, single
      center, observational study, LAAO was performed in patients with previous ICH and
      AF using the Amplatzer Cardiac Plug device. Risks of ischemic strokes and
      hemorrhagic complications were estimated using the CHA2DS2Vasc score and the HAS
      BLED score. Before and 1, 6, 12, and 24 months after the procedure, clinical
      status and complications were recorded. Major complications were predefined as
      periprocedural stroke, death, pericardial effusion, and device embolism. RESULTS:
      LAAO was performed in 20 patients. Based on CHA2DS2Vasc score (mean 4.5 +/- 1.4)
      and HAS-BLED score (mean 4.7 +/- 1.0), annual risks of stroke and hemorrhagic
      complications were 4.0%-6.7% and 8.7%-12.5%, respectively. No patient had a
      procedure-related complication. Minor postprocedural complications were observed
      in 4/20 patients (2 inguinal hematoma, 1 self-limiting asystole, and 1 thrombus
      formation on device). No ischemic or hemorrhagic stroke occurred during a mean
      follow-up of 13.6 +/- 8.2 months. CONCLUSIONS: In this first study of LAAO in
      patients with previous ICH, LAAO appears feasible and safe. A larger, controlled
      trial is needed to assess the efficacy and safety of the procedure compared to
      other preventive measures. CLASSIFICATION OF EVIDENCE: This study provides Class
      III evidence that in patients with a history of previous ICH and AF, percutaneous
      LAAO is safe and feasible.

PMID- 24319043
TI  - Refractory status epilepticus: what to put down: the anesthetics or the patient?

PMID- 24319044
TI  - Freiberg's infraction: diagnosis and treatment.
AB  - Freiberg's infraction is a condition of cartilage degeneration of the lesser
      metatarsal heads. Adolescent females are the "textbook" patients but both males
      and females may present with this condition later in life. The second and third
      metatarsals are the most commonly affected, while involvement of the fourth and
      fifth is rare. The incidence is higher in females than in males. The
      pathophysiology is unknown, but studies suggest a combination of vascular
      compromise, genetic predisposition, and altered biomechanics. Diagnosis is made
      clinically and imaging is used to confirm. Early in the process, radiographs are
      normal however bone scans may demonstrate a photopenic center with a hyperactive
      collar and magnetic resonance imaging can reveal hypointensity of the metatarsal
      head. As Freiberg's infraction progresses, radiographs show a flattened and
      fragmented metatarsal head. Nonoperative treatment is based on decreasing foot
      pressure and unloading the affected metatarsal. Spontaneous healing with
      remodeling may occur in early stages of the disease. Operative options are dorsal
      closing wedge osteotomies, osteochondral transplant, and resection arthroplasty.
      Currently, we do not understand this disease sufficiently to prevent its
      occurrence. Outcomes of nonoperative and operative management are good to
      excellent and most patients are able to return to previous activity.

PMID- 24319045
TI  - Associations between health and combinations of sickness presence and absence.
AB  - BACKGROUND: The association between sickness presence (SP), sickness absence (SA)
      and health is not well known although research on these phenomena has grown in
      recent years. AIMS: To identify the health outcomes of different combinations of
      self-reported SP and SA while controlling for background and work-related
      factors. METHODS: The study group was a representative three-wave sample of 1886
      employed individuals from the Swedish Working Life Cohort, gathered in 2004-2006.
      Block-wise multiple logistic regression analyses were conducted for combinations
      of self-reported SP and SA, using controls for background, work-related and
      previous health factors. RESULTS: The crude odds ratios showed that health and
      mental well-being were most negatively affected in the group with high SP and SA
      in the preceding year. When differences in individual background, health and work
      related factors were controlled for, distinct significant odds ratios remained.
      The odds ratios for negative health outcomes were between 1.49 (95% CI: 1.02
      2.18) and 2.64 (95% CI: 1.81-3.85) higher among those with both high SP and high
      SA than those with both low SP and low SA. However, the study also indicated that
      individuals with high SP and low SA showed the highest odds ratios for poor
      mental well-being. CONCLUSIONS: The results showed that combinations of frequent
      self-rated SP and SA are related to negative values in the four measured aspects
      of self-reported health 1 year later. Occupational medicine practitioners should
      therefore be concerned particularly with employees who report frequently
      occurring SP and SA.

PMID- 24319046
TI  - Large exophytic angiomyolipoma of the kidney mimicking retroperitoneal
      liposarcoma.

PMID- 24319047
TI  - Kidney volume correlates with tumor diameter in renal cell carcinoma and is
      associated with histological poor prognostic features.
AB  - We aimed to correlate kidney volume (KV) in renal cell carcinoma nephrectomy
      specimens with tumor diameter (TD), macroscopic growth pattern, and histological
      features associated with poor prognosis. Histopathology reports, macroscopic
      specimen photographs, and selected glass slides were retrospectively reviewed. KV
      was approximated to the volume of an ellipsoid. A total of 273 specimens were
      identified with median KV 245 cm(3). Kidneys larger than this contained larger
      tumors (7.5 vs 4.5 cm). KV was significantly greater in tumors of high grade,
      involving perinephric fat, exhibiting venous invasion, and involving renal sinus.
      There was a robust linear correlation between KV and TD (r = 0.602) and a weaker
      correlation between kidney diameter (KD) and TD (r = 0.53). In pT1 tumors, KV (r
      = 0.40) also correlated better with TD than did KD (r = 0.27). By multiple
      regression analysis, both TD and venous invasion independently predicted both KD
      (R (2) = 38.27%) and KV (R (2) = 51.97%). KV and KD correlate well with TD and
      histopathological features of aggressiveness, although KD correlates better
      overall and in the pT1 subset. 

PMID- 24319048
TI  - Respiratory protective equipment reduces occurrence of sensitization to
      laboratory animals.
AB  - BACKGROUND: Respiratory protective equipment (RPE) has been shown to reduce
      exposure to laboratory animal allergens, but there are no studies that have
      examined its effect on the development of sensitization. AIMS: To examine the
      effect of RPE on the risk of sensitization to laboratory animals. METHODS: Survey
      of UK laboratory animal workers conducted between 1999 and 2001. Information was
      recorded on the type of RPE used when first exposed to animals and at the time of
      the survey. Sensitization to rat urinary proteins was assessed using skin-prick
      tests and assays of specific serum IgE antibodies. RESULTS: There were 776
      workers surveyed of whom 228 had been exposed for fewer than 5 years. Those more
      recently employed were more likely to have used RPE. In employees with <5 years
      of exposure the use of face masks at first employment was associated with a lower
      prevalence of sensitization, irrespective of the intensity of exposure to
      laboratory animals. This reduction was significant only in those who entered the
      animal house daily. CONCLUSIONS: The use of simple RPE at first exposure to
      laboratory animals may help to reduce the incidence of specific sensitization.

PMID- 24319049
TI  - Bronchiolitis obliterans organizing pneumonia following nitric acid fume
      exposure.
AB  - We describe a patient with clinical, radiological and pathological features of
      bronchiolitis obliterans organizing pneumonia. Investigation showed that this was
      likely to have been a delayed consequence of inhalation of nitric acid fumes
      (containing nitrogen dioxide) after a fire. This case shows that thorough
      investigation of the aetiology is important not only in clinical management but
      also in ensuring patients benefit from appropriate work injury compensation. 

PMID- 24319050
TI  - Association between severity of knee osteoarthritis and serum and synovial fluid
      interleukin 17 concentrations.
AB  - OBJECTIVE: To determine interleukin (IL)-17 concentrations in serum and synovial
      fluid from patients with knee osteoarthritis, and evaluate their correlation with
      disease severity. METHODS: Serum and synovial fluid were collected from patients
      with primary knee osteoarthritis; age- and sex-matched healthy control subjects
      provided serum samples. This study was conducted retrospectively. IL-17 was
      quantified by enzyme-linked immunosorbent assay. Osteoarthritis severity and
      grade were assessed using the Lequesne index and Kellgren and Lawrence (KL)
      grading system, respectively. RESULTS: Serum IL-17 concentrations were
      significantly higher in patients (n = 98) than in controls (n = 50). In the
      patient group, the synovial fluid IL-17 concentration increased significantly
      with KL grade and was significantly positively correlated with Lequesne index (r
      = 0.6232). CONCLUSIONS: The synovial fluid IL-17 concentration could represent a
      useful biochemical marker to reflect knee osteoarthritis severity and
      progression.

PMID- 24319051
TI  - Evaluation of plasma endothelial microparticles in pre-eclampsia.
AB  - OBJECTIVE: To compare the antepartum and postpartum plasma concentrations of
      endothelial microparticles (EMPs) in patients with pre-eclampsia with those of
      healthy control subjects with normal pregnancies. METHODS: Plasma concentrations
      of EMPs were measured using specific antibody labelling and flow cytometry prior
      to delivery by caesarean section (antepartum), and again at 24 h and 72 h
      postpartum. The correlations between EMP concentration and mean arterial pressure
      (MAP), and between EMP concentration and 24-h urine protein were analysed.
      RESULTS: A total of 59 patients with pre-eclampsia and 60 healthy control
      subjects participated in the study. The antepartum plasma EMP concentration was
      significantly higher in patients with pre-eclampsia than in healthy control
      subjects with normal pregnancies (2863.5 +/- 1543.1 versus 1703.0 +/- 592.2 
      EMPs/ml, respectively); similar findings were observed at 24 h postpartum (1836.7
      +/- 1153.8 versus 1421.8 +/- 760.2  EMPs/ml, respectively). There was no
      significant difference between the two groups at 72 h postpartum. The antepartum
      plasma EMP concentration in patients with pre-eclampsia demonstrated a
      significant positive correlation with MAP (r = 0.716) and with 24-h urine protein
      (r = 0.770). CONCLUSION: Plasma EMP concentration might serve as a biomarker to
      evaluate the severity of pre-eclampsia in the future.

PMID- 24319053
TI  - The relationship between working status and symptoms, quality of life and self
      esteem in patients with schizophrenia in Turkey.
AB  - BACKGROUND: Schizophrenia is a severe mental disorder with substantial
      socioeconomic burden associated with poorer psychosocial functioning during the
      course of illness. In schizophrenia patients, multiple factors play a role in
      occupational functioning. AIM: It was aimed to investigate the relationship
      between different working conditions and quality of life and self-esteem on
      patients with schizophrenia in Turkey. METHODS: A total of 100 patients diagnosed
      as schizophrenic were divided into three groups: competitive working, supported
      working and unemployed. RESULTS: The groups did not differ significantly with
      regard to psychotic symptoms, self-esteem and illness history. Working was
      associated with higher scores on quality of life subscales especially in
      supported working group, whereas unemployed patients had more depressive symptoms
      and autonomic drug side effects. CONCLUSION: Structured working programs which
      may improve social life of patients with schizophrenia in many aspects is
      warranted in Turkey.

PMID- 24319054
TI  - Poly(vinylidene-trifluoroethylene)/barium titanate composite for in vivo support
      of bone formation.
AB  - In this study, we evaluated the effect of poly(vinylidene fluoride
      trifluoroethylene)/barium titanate (P(VDF-TrFE)/BT) membrane on in vivo bone
      formation. Rat calvarial bone defects were implanted with P(VDF-TrFE)/BT and
      polytetrafluoroethylene (PTFE) membranes, and at 4 and 8 weeks, histomorphometric
      and gene expression analyses were performed. A higher amount of bone formation
      was noticed on P(VDF-TrFE)/BT compared with PTFE. The gene expression of RUNX2,
      bone sialoprotein, osteocalcin, receptor activator of nuclear factor-kappa B
      ligand, and osteoprotegerin indicates that P(VDF-TrFE)/BT favored the osteoblast
      differentiation compared with PTFE. These results evidenced the benefits of using
      P(VDF-TrFE)/BT to promote new bone formation, which may represent a promising
      alternative to be employed in guided bone regeneration.

PMID- 24319055
TI  - Novel protein interactions with endoglin and activin receptor-like kinase 1:
      potential role in vascular networks.
AB  - Endoglin and activin receptor-like kinase 1 are specialized transforming growth
      factor-beta (TGF-beta) superfamily receptors, primarily expressed in endothelial
      cells. Mutations in the corresponding ENG or ACVRL1 genes lead to hereditary
      hemorrhagic telangiectasia (HHT1 and HHT2 respectively). To discover proteins
      interacting with endoglin, ACVRL1 and TGF-beta receptor type 2 and involved in
      TGF-beta signaling, we applied LUMIER, a high-throughput mammalian interactome
      mapping technology. Using stringent criteria, we identified 181 novel unique and
      shared interactions with ACVRL1, TGF-beta receptor type 2, and endoglin, defining
      potential novel important vascular networks. In particular, the regulatory
      subunit B-beta of the protein phosphatase PP2A (PPP2R2B) interacted with all
      three receptors. Interestingly, the PPP2R2B gene lies in an interval in linkage
      disequilibrium with HHT3, for which the gene remains unidentified. We show that
      PPP2R2B protein interacts with the ACVRL1/TGFBR2/endoglin complex and recruits
      PP2A to nitric oxide synthase 3 (NOS3). Endoglin overexpression in endothelial
      cells inhibits the association of PPP2R2B with NOS3, whereas endoglin-deficient
      cells show enhanced PP2A-NOS3 interaction and lower levels of endogenous NOS3
      Serine 1177 phosphorylation. Our data suggest that endoglin regulates NOS3
      activation status by regulating PPP2R2B access to NOS3, and that PPP2R2B might be
      the HHT3 gene. Furthermore, endoglin and ACVRL1 contribute to several novel
      networks, including TGF-beta dependent and independent ones, critical for
      vascular function and potentially defective in HHT. 

PMID- 24319056
TI  - Global analysis of cdc14 dephosphorylation sites reveals essential regulatory
      role in mitosis and cytokinesis.
AB  - Degradation of the M phase cyclins triggers the exit from M phase. Cdc14 is the
      major phosphatase required for the exit from the M phase. One of the functions of
      Cdc14 is to dephosphorylate and activate the Cdh1/APC/C complex, resulting in the
      degradation of the M phase cyclins. However, other crucial targets of Cdc14 for
      mitosis and cytokinesis remain to be elucidated. Here we systematically analyzed
      the positions of dephosphorylation sites for Cdc14 in the budding yeast
      Saccharomyces cerevisiae. Quantitative mass spectrometry identified a total of
      835 dephosphorylation sites on 455 potential Cdc14 substrates in vivo. We
      validated two events, and through functional studies we discovered that Cdc14
      mediated dephosphorylation of Smc4 and Bud3 is essential for proper mitosis and
      cytokinesis, respectively. These results provide insight into the Cdc14-mediated
      pathways for exiting the M phase. 

PMID- 24319057
TI  - Correlation of actin crosslinker and capper expression levels with stereocilia
      growth phases.
AB  - During development of the chick cochlea, actin crosslinkers and barbed-end
      cappers presumably influence growth and remodeling of the actin paracrystal of
      hair cell stereocilia. We used mass spectrometry to identify and quantify major
      actin-associated proteins of the cochlear sensory epithelium from E14 to E21,
      when stereocilia widen and lengthen. Tight actin crosslinkers (i.e. fascins,
      plastins, and espin) are expressed dynamically during cochlear epithelium
      development between E7 and E21, with FSCN2 replacing FSCN1 and plastins remaining
      low in abundance. Capping protein, a barbed-end actin capper, is located at
      stereocilia tips; it is abundant during growth phase II, when stereocilia have
      ceased elongating and are increasing in diameter. Capping protein levels then
      decline during growth phase III, when stereocilia reinitiate barbed-end
      elongation. Although actin crosslinkers are readily detected by electron
      microscopy in developing chick cochlea stereocilia, quantitative mass
      spectrometry of stereocilia isolated from E21 chick cochlea indicated that tight
      crosslinkers are present there in stoichiometric ratios relative to actin that
      are much lower than their ratios for vestibular stereocilia. These results
      demonstrate the value of quantitation of global protein expression in chick
      cochlea during stereocilia development. 

PMID- 24319059
TI  - Atypical, abscessated nasopharyngeal polyp associated with expansion and lysis of
      the tympanic bulla.
AB  - A 5-year-old, male neutered domestic shorthair cat was referred for investigation
      of lethargy, weight loss, pyrexia and upper respiratory tract signs. On computed
      tomography, an expansile, osteodestructive lesion in the right tympanic bulla was
      identified. A soft tissue mass extended from the bulla into the nasopharynx,
      cranium and subcutaneous tissues. The nasopharyngeal mass ruptured during
      handling, liberating purulent material from which Pasteurella multocida was
      isolated in pure culture. The lesion was most likely an atypical, abscessated
      nasopharyngeal polyp. The cat was treated with bulla osteotomy and antibiotics,
      and made a complete recovery. 

PMID- 24319058
TI  - Both targeted mass spectrometry and flow sorting analysis methods detected the
      decreased serum apolipoprotein E level in Alzheimer's disease patients.
AB  - Apolipoprotein E (ApoE) polymorphism has been appreciated as a valuable predictor
      of Alzheimer disease (AD), and the associated epsilon4 allele has been recognized
      as an indicator of susceptibility to this disease. However, serum ApoE levels
      have been a controversial issue in AD, due to the great variability regarding the
      different target detection methods, ethnicity, and the geographic variations of
      cohorts. The aim of this study was to validate serum ApoE levels in relation to
      AD, particularly using two distinct detection methods, liquid chromatography
      selected reaction monitoring (SRM) mass spectrometry and microsphere-based
      fluorescence-activated cell sorting (FACS) analysis, to overcome experimental
      variations. Also, comparison of serum ApoE levels was performed between the level
      of protein detection by FACS and peptide level by SRM in both control and AD
      patients. Results from the two detection methods were cross-confirmed and
      validated. Both methods produced fairly consistent results, showing a significant
      decrease of serum ApoE levels in AD patients relative to those of a control
      cohort (43 control versus 45 AD, p < 0.0001). Significant correlation has been
      revealed between results from FACS and SRM (p < 0.0001) even though lower serum
      ApoE concentration values were measured in protein by FACS analysis than in
      peptide-level detections by SRM. Correlation study suggested that a decrease of
      the serum ApoE level in AD is related to the mini-mental state exam score in both
      results from different experimental methods, but it failed to show consistent
      correlation with age, gender, or clinical dementia rating. 

PMID- 24319060
TI  - Molecular study on selected vector-borne infections in urban stray colony cats in
      northern Italy.
AB  - Feline vector-borne diseases can be caused by a range of pathogens transmitted by
      arthropods. Many of these infections have zoonotic implications, and stray cats
      are potential sentinels for human and pet health. This study investigated the
      prevalence of selected vector-borne infections in stray colony cats in Milan.
      Blood samples from 260 stray cats were evaluated, using conventional polymerase
      chain reaction tests (cPCRs), for the presence of DNA associated with Rickettsia
      species, Anaplasma phagocytophilum and Ehrlichia species. Positive cPCR results
      occurred in 127/260 subjects (48.9%; 95% confidence interval [CI] = 40.7-58.1),
      with a prevalence of 31.9% (83/260, 95% CI = 25.4-39.6) for Rickettsia species,
      17.7% (46/260, 95% CI= 13.0-23.6) for A phagocytophilum, and 5.4% (14/260, 95% CI
      = 2.9-9.0) for Ehrlichia species. There was no statistical association between a
      positive PCR test for vector-borne infections surveyed and colony location, age,
      gender, body condition score or complete blood count abnormalities, nor feline
      immunodeficiency virus, feline leukaemia virus or Toxoplasma gondii status. The
      only variable linked to positive PCR results was detection of signs of ocular
      infection and PCR positivity for Rickettsia species (P = 0.04, odds ratio [OR] =
      2.2, 95% CI = 1.1-4.4, P = 0.02). There is a significant prevalence of vector
      borne infections with zoonotic potential in urban stray cats in Milan. Thus, dogs
      and pet cats with outdoor access should be monitored and treated for
      ectoparasites on a regular basis to minimise risks of disease and the potential
      transmission of zoonotic agents to people. 

PMID- 24319061
TI  - Feiring's concept of forward-looking responsibility: a dead end for
      responsibility in healthcare.
AB  - Eli Feiring has developed a concept of forward-looking responsibility in
      healthcare. On this account, what matters morally in the allocation of scarce
      healthcare resources is not people's past behaviours but rather their commitment
      to take on lifestyles that will increase the benefit acquired from received
      treatment. According to Feiring, this is to be preferred over the backward
      looking concept of responsibility often associated with luck egalitarianism. The
      article critically scrutinises Feiring's position. It begins by spelling out the
      wider implications of Feiring's view. Against this background, it shows that (i)
      Feiring's distinction between backward-looking and forward-looking responsibility
      is incompatible with the Scanlonian notion of responsibility she apparently
      endorses; (ii) her favoured forward-looking notion of responsibility is subject
      to the objections levelled against the luck egalitarian view (whatever the
      strength of such objections). 

PMID- 24319062
TI  - Staying a step ahead of influenza.

PMID- 24319063
TI  - Can evolutionary tools reliably tell us about dengue virus' past outbreaks?

PMID- 24319064
TI  - Plants found to aid their enemies.

PMID- 24319065
TI  - Running hot and cold on the trail to measuring adaptation in fruit flies.

PMID- 24319066
TI  - Everything you wanted to know about honeybee sex.

PMID- 24319067
TI  - Avoiding poisons: a matter of bitter taste?

PMID- 24319072
TI  - Patient-centered men's health.

PMID- 24319070
TI  - Impact of postdiagnosis smoking on long-term survival of cancer patients: the
      Shanghai cohort study.
AB  - BACKGROUND: Cancer is the number one cause of death among men in China. Cigarette
      smoking is the most preventable cause of cancer. Data on the impact of continued
      smoking after cancer diagnosis on survival of patients with cancer are sparse.
      METHODS: We studied the association between postdiagnosis smoking and risk of all
      cause death among 1,632 incident cancer patients in the Shanghai Cohort Study, a
      population-based prospective cohort of 18,244 men in Shanghai. The change of
      smoking status after baseline interview was ascertained through annual in-person
      interviews. Cox proportional hazards regression models were used to estimate HR
      and 95% confidence interval (CI) for all-cause mortality associated with change
      in smoking status. RESULTS: Patients who continued smoking after cancer diagnosis
      experienced a statistically significant 59% (95% CI, 36-86) increase in risk of
      death compared with patients with cancer who did not smoke after cancer
      diagnosis. Among current smokers at cancer diagnosis, HRs (95% CIs) were 1.79
      (1.49-2.16) in all patients with cancer, 2.36 (1.63-3.42) in patients with lung
      cancer, 1.63 (0.98-2.73) in patients with stomach cancer, 2.31 (1.40-3.81) in
      patients with colorectal cancer, and 2.95 (1.09-7.95) in patients with bladder
      cancer who continued smoking compared with their counterparts who stopped smoking
      after cancer diagnosis. CONCLUSION: Postdiagnosis cigarettes smoking
      significantly increased the risk of death for male patients with cancer. IMPACT:
      These data provide new information about smoking and cancer survival, which
      should inform future research into the contextual and individual-level barriers
      that may result in inadequate attention of smoking among patients with cancer in
      the postdiagnosis setting.

PMID- 24319068
TI  - NF-kappaB activation-induced anti-apoptosis renders HER2-positive cells drug
      resistant and accelerates tumor growth.
AB  - Breast cancers with HER2 overexpression are sensitive to drugs targeting the
      receptor or its kinase activity. HER2-targeting drugs are initially effective
      against HER2-positive breast cancer, but resistance inevitably occurs. We
      previously found that NF-kappaB is hyperactivated in a subset of HER2-positive
      breast cancer cells and tissue specimens. In this study, we report that
      constitutively active NF-kappaB rendered HER2-positive cancer cells resistant to
      anti-HER2 drugs and cells selected for lapatinib resistance upregulated NF
      kappaB. In both circumstances, cells were antiapoptotic and grew rapidly as
      xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-kappaB
      inhibitors alone but were sensitive to their combination, suggesting a novel
      therapeutic strategy. A subset of NF-kappaB-responsive genes was overexpressed in
      HER2-positive and triple-negative breast cancers, and patients with this NF
      kappaB signature had poor clinical outcome. Anti-HER2 drug resistance may be a
      consequence of NF-kappaB activation, and selection for resistance results in NF
      kappaB activation, suggesting that this transcription factor is central to
      oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and
      NF-kappaB suggests a potential treatment paradigm for patients who relapse after
      anti-HER2 therapy. Patients with these cancers may be treated by simultaneously
      suppressing HER2 signaling and NF-kappaB activation. IMPLICATIONS: The
      combination of an inhibitor of IkappaB kinase (IKK) inhibitor and anti-HER2 drugs
      may be a novel treatment strategy for drug-resistant human breast cancers.

PMID- 24319073
TI  - Effects of elevated CO2 on levels of primary metabolites and transcripts of genes
      encoding respiratory enzymes and their diurnal patterns in Arabidopsis thaliana:
      possible relationships with respiratory rates.
AB  - Elevated CO2 affects plant growth and photosynthesis, which results in changes in
      plant respiration. However, the mechanisms underlying the responses of plant
      respiration to elevated CO2 are poorly understood. In this study, we measured
      diurnal changes in the transcript levels of genes encoding respiratory enzymes,
      the maximal activities of the enzymes and primary metabolite levels in shoots of
      Arabidopsis thaliana grown under moderate or elevated CO2 conditions (390 or 780
      parts per million by volume CO2, respectively). We examined the relationships
      between these changes and respiratory rates. Under elevated CO2, the transcript
      levels of several genes encoding respiratory enzymes increased at the end of the
      light period, but these increases did not result in changes in the maximal
      activities of the corresponding enzymes. The levels of some primary metabolites
      such as starch and sugar phosphates increased under elevated CO2, particularly at
      the end of the light period. The O2 uptake rate at the end of the dark period was
      higher under elevated CO2 than under moderate CO2, but higher under moderate CO2
      than under elevated CO2 at the end of the light period. These results indicate
      that the changes in O2 uptake rates are not directly related to changes in
      maximal enzyme activities and primary metabolite levels. Instead, elevated CO2
      may affect anabolic processes that consume respiratory ATP, thereby affecting O2
      uptake rates. 

PMID- 24319074
TI  - Genome-wide analysis of intraspecific DNA polymorphism in 'Micro-Tom', a model
      cultivar of tomato (Solanum lycopersicum).
AB  - Tomato (Solanum lycopersicum) is regarded as a model plant of the Solanaceae
      family. The genome sequencing of the tomato cultivar 'Heinz 1706' was recently
      completed. To accelerate the progress of tomato genomics studies, systematic
      bioresources, such as mutagenized lines and full-length cDNA libraries, have been
      established for the cultivar 'Micro-Tom'. However, these resources cannot be
      utilized to their full potential without the completion of the genome sequencing
      of 'Micro-Tom'. We undertook the genome sequencing of 'Micro-Tom' and here report
      the identification of single nucleotide polymorphisms (SNPs) and
      insertion/deletions (indels) between 'Micro-Tom' and 'Heinz 1706'. The analysis
      demonstrated the presence of 1.23 million SNPs and 0.19 million indels between
      the two cultivars. The density of SNPs and indels was high in chromosomes 2, 5
      and 11, but was low in chromosomes 6, 8 and 10. Three known mutations of 'Micro
      Tom' were localized on chromosomal regions where the density of SNPs and indels
      was low, which was consistent with the fact that these mutations were relatively
      new and introgressed into 'Micro-Tom' during the breeding of this cultivar. We
      also report SNP analysis for two 'Micro-Tom' varieties that have been maintained
      independently in Japan and France, both of which have served as standard lines
      for 'Micro-Tom' mutant collections. Approximately 28,000 SNPs were identified
      between these two 'Micro-Tom' lines. These results provide high-resolution DNA
      polymorphic information on 'Micro-Tom' and represent a valuable contribution to
      the 'Micro-Tom'-based genomics resources. 

PMID- 24319075
TI  - Histone H2B monoubiquitination is involved in the regulation of cutin and wax
      composition in Arabidopsis thaliana.
AB  - The plant cuticle is a chemically heterogeneous lipophilic layer composed of a
      cutin polymer matrix and waxes which covers the aerial parts of plants. This
      layer plays an essential role in the survival of plants by protecting them from
      desiccation and (a)biotic stresses. Knowledge on the gene networks and mechanisms
      regulating the synthesis of cuticle components during organ expansion or stress
      response remains limited however. Here, using five loss-of-function mutants for
      histone monoubiquitination, we report on the role of two RING E3 ligases, namely
      HISTONE MONOUBIQUITINATION 1 and 2 (HUB1 and HUB2), in the selective
      transcriptional activation of four cuticle biosynthesis genes in Arabidopsis
      thaliana. Microscopy observations showed that in hub1-6 and hub2-2 mutants
      irregular epidermal cells and disorganized cuticle layers were present in rosette
      leaves. Water loss measurements on excised rosettes demonstrated that cuticular
      permeability was significantly increased in the mutants. Chemical analysis of
      cuticle components revealed that the wax composition was changed and that cutin
      16:0 dicarboxylic acid was significantly reduced in all hub mutants. Analysis of
      transcript levels of selected genes indicated that LACS2, ATT1 and HOTHEAD
      involved in cutin biosynthesis and CER1 involved in wax biosynthesis were down
      regulated in the hub mutants, while the expression of LACERATA, CER3, CER6 and
      CER10 remained unchanged. Chromatin immunoprecipitation assays further showed
      that hub mutants are impaired in dynamic changes of histone H2B
      monoubiquitination at several loci of down-regulated genes. Taken together, these
      data establish that the regulation of cuticle composition involves chromatin
      remodeling by H2B monoubiquitination. 

PMID- 24319076
TI  - AtMYB7, a new player in the regulation of UV-sunscreens in Arabidopsis thaliana.
AB  - The phenylpropanoid metabolic pathway provides a wide variety of essential
      compounds for plants. Together with sinapate esters, in Brassicaceae species,
      flavonoids play an important role in protecting plants against UV irradiation. In
      this work we have characterized Arabidopsis thaliana AtMYB7, the closest homolog
      of AtMYB4 and AtMYB32, described as repressors of different branches of
      phenylpropanoid metabolism. The characterization of atmyb7 plants revealed an
      induction of several genes involved in flavonol biosynthesis and an increased
      amount of these compounds. In addition, AtMYB7 gene expression is repressed by
      AtMYB4. As a consequence, the atmyb4 mutant plants present a reduction of
      flavonol contents, indicating once more that AtMYB7 represses flavonol
      biosynthesis. Our results also show that AtMYB7 gene expression is induced by
      salt stress. Induction assays indicated that AtMYB7 represses several genes of
      the flavonoid pathway, DFR and UGT being early targets of this transcription
      factor. The results obtained indicate that AtMYB7 is a repressor of flavonol
      biosynthesis and also led us to propose AtMYB4 and AtMYB7 as part of the
      regulatory mechanism controlling the balance of the main A. thaliana UV
      sunscreens. 

PMID- 24319077
TI  - Effects of high CO2 on growth and metabolism of Arabidopsis seedlings during
      growth with a constantly limited supply of nitrogen.
AB  - Elevated CO2 has been reported to stimulate plant growth under nitrogen
      sufficient conditions, but the effects of CO2 on growth in a constantly nitrogen
      limited state, which is relevant to most natural habitats of plants, remain
      unclear. Here, we maintained Arabidopsis seedlings under such conditions by
      growing a mutant with reduced nitrate uptake activity on a medium containing
      nitrate as the sole nitrogen source. Under nitrogen-sufficient conditions (i.e.
      in the presence of ammonium), growth of shoots and roots of both the wild type
      (WT) and the mutant was increased approximately 2-fold by elevated CO2. Growth
      stimulation of shoots and roots by elevated CO2 was observed in the WT growing
      with nitrate as the sole nitrogen source, but in the mutant grown with nitrate,
      the high-CO2 conditions stimulated only the growth of roots. In the mutant,
      elevated CO2 caused well-known symptoms of nitrogen-starved plants, including
      decreased shoot/root ratio, reduced nitrate content and accumulation of
      anthocyanin, but also had an increased Chl content in the shoot, which was
      contradictory to the known effect of nitrogen depletion. A high-CO2-responsive
      change specific to the mutant was not observed in the levels of the major
      metabolites, although CO2 responses were observed in the WT and the mutant. These
      results indicated that elevated CO2 causes nitrogen limitation in the seedlings
      grown with a constantly limited supply of nitrogen, but the Chl content and the
      root biomass of the plant increase to enhance the activities of both
      photosynthesis and nitrogen uptake, while maintaining normal metabolism and
      response to high CO2. 

PMID- 24319078
TI  - Assessing the potential of e-mail for communicating drug therapy recommendations
      to physicians in patients with heart failure and ventricular-assist devices.
AB  - PURPOSE: This project explores electronic mail (e-mail) as a potential medium for
      pharmacists to communicate pharmacotherapy interventions to prescribers. METHODS:
      This retrospective descriptive analysis was conducted at an urban, academic
      teaching hospital. The pharmacist attempted a drug therapy intervention via e
      mail when unable to make face-to-face contact with the attending physician.
      Eligible patients for this project were admitted to the advanced heart failure
      (HF) team between December 1, 2010, and July 31, 2011, and had at least 1
      attempted e-mail intervention. The primary outcome was the number of accepted
      interventions, while the secondary end point was the time until a physician e
      mail response. RESULTS: A total of 51 e-mail interventions were attempted on 29
      patients (mean age = 53, 24% caucasian, 59% male, 69% left ventricular-assist
      device [VAD]). Overall, of the total 51 interventions,44 (86.3%) were accepted.
      The average time to a physician e-mail response was 41 minutes. Initiation of
      drug therapy and changing dose and route or frequency accounted for the most
      frequent intervention (33%). The most common drug classes involved in the e-mail
      interventions were angiotensin-converting enzyme inhibitors (15.7%), loop
      diuretics (9.8%), and antiplatelet agents (7.8%). CONCLUSION: Clinical
      pharmacists with well-established physician relationships can effectively
      implement timely drug therapy recommendations using e-mail communications in
      patients with advanced HF or VADs.

PMID- 24319079
TI  - Adverse drug events in critically ill patients with cancer: incidence,
      characteristics, and outcomes.
AB  - OBJECTIVE: To determine the incidence, characteristics, and outcomes of adverse
      drug events (ADEs) in critically ill patients with cancer. METHODS: This was a 5
      month prospective observational study. Patients who were admitted to the adult
      medical/surgical oncology intensive care unit (ICU) were evaluated for any drug
      related adverse events during their ICU stay. An ADE was defined as injury or
      patient harm resulting from medical intervention related to a drug. RESULTS: The
      incidence rate of ADEs was 96.5 per 1000 patient days and 35.3 per 100 ICU
      admissions. Of the reported ADEs, 57 (64.8%) were serious/life threatening, 30
      (34.1%) were significant, 1 (1.1%) was fatal, and 14 (15.9%) of all ADEs were
      considered preventable. The most common drug classes associated with ADEs were
      antidiabetics, antibiotics, and analgesics/sedatives. The length of stay and
      presence of renal or respiratory failure were significantly associated with an
      increased number of ADEs. The length of stay and female sex were significantly
      associated with the likelihood of developing an ADE. CONCLUSION: Critically ill
      patients with cancer are at high risk of developing ADEs. Strategies that reduce
      the incidence and severity of ADEs are essential to improve the outcomes of this
      patient population.

PMID- 24319080
TI  - Dabigatran Use in the Real World: A Multihospital System Experience.
AB  - Dabigatran etexilate, an oral direct thrombin inhibitor, was approved by the Food
      and Drug Administration to reduce the risk of stroke and systemic embolism in
      patients with nonvalvular atrial fibrillation based on the outcomes of the
      Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) study. Although
      this study provides robust data on the efficacy and safety of dabigatran, there
      may be differences in the drug use and outcomes in routine clinical practice
      following drug approval. In this retrospective chart review study, we describe
      the use of dabigatran in 160 patients in 4 adult hospitals (1 academic and 3
      community), including appropriate prescribing for indication, starting dose,
      concomitant anticoagulant and antiplatelet use, and clinical outcomes such as
      bleeding, myocardial infarction, and stroke. The study revealed appropriate
      indication of nonvalvular atrial fibrillation in 145 (91%) of the 160 patients.
      The dose of dabigatran was appropriate in 90% of the patients, with the most
      common cause of inappropriate dosing due to perceived bleeding risk. Over a
      follow-up period of 6 months, bleeding complications were noted in 6 patients
      still taking dabigatran, 5 of which were gastrointestinal bleeding. Our study
      underscores the importance of prescriber education regarding the appropriate
      indication, dosage, and safety of dabigatran with active participation of
      pharmacists in this process. 

PMID- 24319081
TI  - The high polyphenol content of grapevine cultivar tannat berries is conferred
      primarily by genes that are not shared with the reference genome.
AB  - The grapevine (Vitis vinifera) cultivar Tannat is cultivated mainly in Uruguay
      for the production of high-quality red wines. Tannat berries have unusually high
      levels of polyphenolic compounds, producing wines with an intense purple color
      and remarkable antioxidant properties. We investigated the genetic basis of these
      important characteristics by sequencing the genome of the Uruguayan Tannat clone
      UY11 using Illumina technology, followed by a mixture of de novo assembly and
      iterative mapping onto the PN40024 reference genome. RNA sequencing data for
      genome reannotation were processed using a combination of reference-guided
      annotation and de novo transcript assembly, allowing 5901 previously unannotated
      or unassembled genes to be defined and resulting in the discovery of 1873 genes
      that were not shared with PN40024. Expression analysis showed that these cultivar
      specific genes contributed substantially (up to 81.24%) to the overall expression
      of enzymes involved in the synthesis of phenolic and polyphenolic compounds that
      contribute to the unique characteristics of the Tannat berries. The
      characterization of the Tannat genome therefore indicated that the grapevine
      reference genome lacks many genes that appear to be relevant for the varietal
      phenotype. 

PMID- 24319082
TI  - The endoplasmic reticulum binding protein BiP displays dual function in
      modulating cell death events.
AB  - The binding protein (BiP) has been demonstrated to participate in innate immunity
      and attenuate endoplasmic reticulum- and osmotic stress-induced cell death. Here,
      we employed transgenic plants with manipulated levels of BiP to assess whether
      BiP also controlled developmental and hypersensitive programmed cell death (PCD).
      Under normal conditions, the BiP-induced transcriptome revealed a robust down
      regulation of developmental PCD genes and an up-regulation of the genes involved
      in hypersensitive PCD triggered by nonhost-pathogen interactions. Accordingly,
      the BiP-overexpressing line displayed delayed leaf senescence under normal
      conditions and accelerated hypersensitive response triggered by Pseudomonas
      syringae pv tomato in soybean (Glycine max) and tobacco (Nicotiana tabacum), as
      monitored by measuring hallmarks of PCD in plants. The BiP-mediated delay of leaf
      senescence correlated with the attenuation of N-rich protein (NRP)-mediated cell
      death signaling and the inhibition of the senescence-associated activation of the
      unfolded protein response (UPR). By contrast, under biological activation of
      salicylic acid (SA) signaling and hypersensitive PCD, BiP overexpression further
      induced NRP-mediated cell death signaling and antagonistically inhibited the UPR.
      Thus, the SA-mediated induction of NRP cell death signaling occurs via a pathway
      distinct from UPR. Our data indicate that during the hypersensitive PCD, BiP
      positively regulates the NRP cell death signaling through a yet undefined
      mechanism that is activated by SA signaling and related to ER functioning. By
      contrast, BiP's negative regulation of leaf senescence may be linked to its
      capacity to attenuate the UPR activation and NRP cell death signaling. Therefore,
      BiP can function either as a negative or positive modulator of PCD events. 

PMID- 24319083
TI  - Are we prepped for preexposure prophylaxis (PrEP)? Provider opinions on the real
      world use of PrEP in the United States and Canada.
AB  - BACKGROUND:  Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate
      and emtricitabine (Truvada) has demonstrated efficacy in placebo-controlled
      clinical trials involving men who have sex with men, high-risk heterosexuals,
      serodiscordant couples, and intravenous drug users. To assist in the real-world
      provision of PrEP, the Centers for Disease Control and Prevention (CDC) has
      released guidance documents for PrEP use. METHODS:  Adult infectious disease
      physicians were surveyed about their opinions and current practices of PrEP
      through the Emerging Infections Network (EIN). Geographic information systems
      analysis was used to map out provider responses across the United States.
      RESULTS:  Of 1175 EIN members across the country, 573 (48.8%) responded to the
      survey. A majority of clinicians supported PrEP but only 9% had actually provided
      it. Despite CDC guidance, PrEP practices were variable and clinicians reported
      many barriers to its real-world provision. CONCLUSIONS:  The majority of adult
      infectious disease physicians across the United States and Canada support PrEP
      but have vast differences of opinion and practice, despite the existence of CDC
      guidance documents. The success of real-world PrEP will likely require
      multifaceted programs addressing barriers to its provision and will be assisted
      with the development of comprehensive guidelines for real-world PrEP.

PMID- 24319085
TI  - Severe acute respiratory syndrome beyond Amoy Gardens: completing the incomplete
      legacy.
AB  - The temporal and spatial distributions of the 2003 severe acute respiratory
      syndrome (SARS) outbreak in Amoy Gardens of Hong Kong was reexamined using all
      confirmed cases. The outbreak actually extended to nearby residential complexes.
      Airborne spread was the most likely explanation, and the SARS coronavirus could
      have spread over a distance of 200 m. 

PMID- 24319084
TI  - Determinants of mortality in a combined cohort of 501 patients with HIV
      associated Cryptococcal meningitis: implications for improving outcomes.
AB  - BACKGROUND:  Cryptococcal meningitis (CM) is a leading cause of death in
      individuals infected with human immunodeficiency virus (HIV). Identifying factors
      associated with mortality informs strategies to improve outcomes. METHODS:  Five
      hundred one patients with HIV-associated CM were followed prospectively for 10
      weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African
      patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria
      were applied at all sites. Logistic regression identified baseline variables
      independently associated with mortality. RESULTS:  Mortality was 17% at 2 weeks
      and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence
      interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4
      per log10 colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50
      years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 *
      10(9) cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment,
      and slow clearance of CSF infection were independently associated with 2-week
      mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening
      pressure were independently associated with mortality at 10 weeks in addition to
      altered mental status, high fungal burden, high peripheral white cell count, and
      older age. In those followed for 1 year, overall mortality was 41%. Immune
      reconstitution inflammatory syndrome occurred in 13% of patients and was
      associated with 2-week CSF fungal burden (P = .007), but not with time to
      initiation of antiretroviral therapy (ART). CONCLUSIONS:  CSF fungal burden,
      altered mental status, and rate of clearance of infection predict acute mortality
      in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly
      fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART
      are priorities for improving outcomes.

PMID- 24319086
TI  - What is a journal?

PMID- 24319089
TI  - "Like a sound and its echo". Biventricular pulsus alternans.

PMID- 24319090
TI  - Interrogating congenital heart defects with noninvasive fetal echocardiography in
      a mouse forward genetic screen.
AB  - BACKGROUND: Congenital heart disease (CHD) has a multifactorial pathogenesis, but
      a genetic contribution is indicated by heritability studies. To investigate the
      spectrum of CHD with a genetic pathogenesis, we conducted a forward genetic
      screen in inbred mice using fetal echocardiography to recover mutants with CHD.
      Mice are ideally suited for these studies given that they have the same four
      chamber cardiac anatomy that is the substrate for CHD. METHODS AND RESULTS:
      Ethylnitrosourea mutagenized mice were ultrasound-interrogated by fetal
      echocardiography using a clinical ultrasound system, and fetuses suspected to
      have cardiac abnormalities were further interrogated with an ultrahigh-frequency
      ultrasound biomicroscopy. Scanning of 46 270 fetuses revealed 1722 with cardiac
      anomalies, with 27.9% dying prenatally. Most of the structural heart defects can
      be diagnosed using ultrasound biomicroscopy but not with the clinical ultrasound
      system. Confirmation with analysis by necropsy and histopathology showed
      excellent diagnostic capability of ultrasound biomicroscopy for most CHDs.
      Ventricular septal defect was the most common CHD observed, whereas outflow tract
      and atrioventricular septal defects were the most prevalent complex CHD.
      Cardiac/visceral organ situs defects were observed at surprisingly high
      incidence. The rarest CHD found was hypoplastic left heart syndrome, a phenotype
      never seen in mice previously. CONCLUSIONS: We developed a high-throughput, 2
      tier ultrasound phenotyping strategy for efficient recovery of even rare CHD
      phenotypes, including the first mouse models of hypoplastic left heart syndrome.
      Our findings support a genetic pathogenesis for a wide spectrum of CHDs and
      suggest that the disruption of left-right patterning may play an important role
      in CHD.

PMID- 24319091
TI  - Two types of event memory.

PMID- 24319093
TI  - 2-Hydroxyglutarate is not a metabolite; D-2-hydroxyglutarate and L-2
      hydroxyglutarate are!

PMID- 24319094
TI  - Prognosis and management of chronic kidney disease (CKD) at the end of life.
AB  - The prevalence of chronic kidney disease (CKD) increases with age. As people are
      living longer, nephrologists are responsible for a progressively older cohort of
      patients with substantial comorbidities. Patients with CKD have a significant
      symptom burden and can benefit from intervention and symptom control from an
      early stage in the illness. It is also increasingly recognised that renal
      replacement therapy may not always offer an improvement in symptoms or a survival
      advantage to older patients with high levels of comorbidity. For these reasons,
      non-dialytic (conservative) management and end-of-life care is becoming part of
      routine nephrology practice. Such patients will also frequently be encountered in
      other specialities, requiring generalists to have some renal-specific skills and
      knowledge. Although there have been significant advances in this field in recent
      years, the optimum model of care and some of the care preferences of patients
      remain challenges that need to be addressed. 

PMID- 24319092
TI  - QsIA disrupts LasR dimerization in antiactivation of bacterial quorum sensing.
AB  - The human pathogen Pseudomonas aeruginosa coordinates the expression of virulence
      factors by using quorum sensing (QS), a signaling cascade triggered by the QS
      signal molecule and its receptor, a member of the LuxR family of QS
      transcriptional factors (LasR). The QS threshold and response in P. aeruginosa is
      defined by a QS LasR-specific antiactivator (QslA), which binds to LasR and
      prevents it from binding to its target promoter. However, how QslA binds to LasR
      and regulates its DNA binding activity in QS remains elusive. Here we report the
      crystal structure of QslA in complex with the N-terminal ligand binding domain of
      LasR. QsIA exists as a functional dimer to interact with the LasR ligand binding
      domain. Further analysis shows that QsIA binding occupies the LasR dimerization
      interface and consequently disrupts LasR dimerization, thereby preventing LasR
      from binding to its target DNA and disturbing normal QS. Our findings provide a
      structural model for understanding the QslA-mediated antiactivation mechanism in
      QS through protein-protein interaction. 

PMID- 24319096
TI  - Clinical reminders to providers of patients with reduced left ventricular
      ejection fraction increase defibrillator referral: a randomized trial.
AB  - BACKGROUND: Many patients who are candidates for implantable cardioverter
      defibrillators (ICDs) are not referred for potential implantation. We sought to
      determine if a simple provider reminder would increase referrals. METHODS AND
      RESULTS: We identified consecutive patients from January 2007 through July 2010
      in the VA Palo Alto Health Care System with a left ventricular ejection
      fraction<35% on echocardiography. Patients were excluded using available
      administrative data only (no chart review) if they were known to have an ICD, if
      they were >=80 years old, or if they did not have a current primary care or
      cardiology provider within the system. We randomized patients to no intervention
      or a clinical note to the provider in the medical record. The outcomes were
      referral for consideration of defibrillator implantation (primary) and documented
      discussion (secondary). Of 330 patients with left ventricular ejection
      fraction<=35%, 128 were known to have an ICD, 85 were no longer followed in the
      healthcare system, and 28 were >=80 years old, leaving 89 patients to be
      randomized. Forty-six patients were randomized to intervention and 43 to control.
      Eleven of 46 (24%) intervention patients were referred for consideration of ICD
      implantation during the following 6 months versus 1 of 43 (2%) control patients
      (P=0.004). Overall, 31 of 46 (67%) intervention patients versus 19 of 43 (44%)
      control patients had documentation discussing potential candidacy for
      defibrillators (P=0.05). CONCLUSIONS: In patients with low left ventricular
      ejection fraction, a simple electronic medical record-based intervention directed
      to their providers improved the rates of referral for ICD implantation. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01217827.

PMID- 24319097
TI  - Unilateral lingual paralysis after isolated unilateral infarction in the primary
      motor cortex.

PMID- 24319095
TI  - Deep sequence analysis of gene expression identifies osteopontin as a downstream
      effector of integrin-linked kinase (ILK) in cardiac-specific ILK knockout mice.
AB  - BACKGROUND: Integrin-linked kinase (ILK) is a serine/threonine kinase that has
      been linked to human and experimental heart failure, but its role in the heart is
      not fully understood. METHODS AND RESULTS: To define the role of cardiomyocyte
      ILK, we generated cardiac-specific ILK knockout mice using alpha-myosin heavy
      chain-driven Cre expression. Cardiac-specific ILK knockout mice spontaneously
      developed lethal dilated cardiomyopathy and heart failure with an early increase
      in apoptosis, fibrosis, and cardiac inflammation. To identify downstream
      effectors, we used deep sequence analysis of gene expression to compare
      comprehensive transcriptional profiles of cardiac-specific ILK knockout and wild
      type hearts from 10-day-old mice before the development of cardiac dysfunction.
      Approximately 2*10(6) cDNA clones from each genotype were sequenced,
      corresponding to 33 274 independent transcripts. A total of 93 genes were
      altered, using nominal thresholds of >1.4-fold change and P<0.001. The most
      highly upregulated gene was osteopontin (47-fold increase; P=9.6*10(-45)), an
      inflammatory chemokine implicated in heart failure pathophysiology. ILK also
      regulated osteopontin expression in cardiomyocytes in vitro. Importantly,
      blocking antibodies to osteopontin mitigated but did not fully rescue the
      functional decline in cardiac-specific ILK knockout mice. CONCLUSIONS:
      Cardiomyocyte-specific ILK deletion leads to a lethal cardiomyopathy
      characterized by cardiomyocyte death, fibrosis, and inflammation. Comprehensive
      profiling identifies ILK-dependent transcriptional effects and implicates
      osteopontin as a contributor to these phenotypes.

PMID- 24319098
TI  - A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis
      imperfecta.
AB  - We identified a family in which pitted hypomineralized amelogenesis imperfecta
      (AI) with premature enamel failure segregated in an autosomal recessive fashion.
      Whole-exome sequencing revealed a missense mutation (c.586C>A, p.P196T) in the I
      domain of integrin-beta6 (ITGB6), which is consistently predicted to be
      pathogenic by all available programmes and is the only variant that segregates
      with the disease phenotype. Furthermore, a recent study revealed that mice
      lacking a functional allele of Itgb6 display a hypomaturation AI phenotype.
      Phenotypic characterization of affected human teeth in this study showed areas of
      abnormal prismatic organization, areas of low mineral density and severe abnormal
      surface pitting in the tooth's coronal portion. We suggest that the pathogenesis
      of this form of AI may be due to ineffective ligand binding of ITGB6 resulting in
      either compromised cell-matrix interaction or compromised ITGB6 activation of
      transforming growth factor-beta (TGF-beta) impacting indirectly on ameloblast
      ameloblast interactions and proteolytic processing of extracellular matrix
      proteins via MMP20. This study adds to the list of genes mutated in AI and
      further highlights the importance of cell-matrix interactions during enamel
      formation. 

PMID- 24319100
TI  - Dedifferentiation and aberrations of the endolysosomal compartment characterize
      the early stage of nephropathic cystinosis.
AB  - Nephropathic cystinosis, a lysosomal storage disease caused by mutations in the
      CTNS gene encoding the lysosomal cystine transporter cystinosin, is characterized
      by generalized proximal tubule (PT) dysfunction that progresses, if untreated, to
      end-stage renal disease. The pathogenesis of defective PT cellular transport in
      nephropathic cystinosis remains unclear. We characterized a recently generated
      line of C57BL/6 Ctns mice and analyzed endocytic uptake, lysosome function, and
      dedifferentiation and proliferation markers using primary cultures of PT
      epithelial cells derived from Ctns(-/-) and Ctns(+/+) littermates. Metabolic
      studies revealed that Ctns(-/-) mice show a progressive PT dysfunction
      characterized by low-molecular-weight (LMW) proteinuria, glucosuria and
      phosphaturia, before structural damage and in the absence of renal failure. These
      changes are related to decreased expression of the multi-ligand receptors megalin
      and cubilin and to increased dedifferentiation (ZONAB transcription factor) and
      proliferation (PCNA and Cyclin D1) rates. Studies on PT cells derived from Ctns(
      /-) kidneys confirmed cystine overload, with accumulation of enlarged,
      dysfunctional lysosomes and reduced expression of endocytic receptors reflected
      by decreased uptake of specific ligands. These changes were related to a loss of
      integrity of tight junctions with a nuclear translocation of ZONAB and increased
      proliferation, as observed in Ctns(-/-) kidneys. These data reveal that the
      absence of cystinosin in PT cells triggers aberrations of the endolysosomal
      compartment, transport defects and an abnormal transcription program in the early
      stage of nephropathic cystinosis. Insights into the early manifestations of
      cystinosis may offer new targets for intervention, before irreversible renal
      damage. 

PMID- 24319099
TI  - Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis
      multiplex congenita with axoglial defects.
AB  - Non-syndromic arthrogryposis multiplex congenita (AMC) is characterized by
      multiple congenital contractures resulting from reduced fetal mobility. Genetic
      mapping and whole exome sequencing (WES) were performed in 31 multiplex and/or
      consanguineous undiagnosed AMC families. Although this approach identified known
      AMC genes, we here report pathogenic mutations in two new genes. Homozygous
      frameshift mutations in CNTNAP1 were found in four unrelated families. Patients
      showed a marked reduction in motor nerve conduction velocity (<10 m/s) and
      transmission electron microscopy (TEM) of sciatic nerve in the index cases
      revealed severe abnormalities of both nodes of Ranvier width and myelinated
      axons. CNTNAP1 encodes CASPR, an essential component of node of Ranvier domains
      which underlies saltatory conduction of action potentials along the myelinated
      axons, an important process for neuronal function. A homozygous missense mutation
      in adenylate cyclase 6 gene (ADCY6) was found in another family characterized by
      a lack of myelin in the peripheral nervous system (PNS) as determined by TEM.
      Morpholino knockdown of the zebrafish orthologs led to severe and specific
      defects in peripheral myelin in spite of the presence of Schwann cells. ADCY6
      encodes a protein that belongs to the adenylate cyclase family responsible for
      the synthesis of cAMP. Elevation of cAMP can mimic axonal contact in vitro and
      upregulates myelinating signals. Our data indicate an essential and so far
      unknown role of ADCY6 in PNS myelination likely through the cAMP pathway.
      Mutations of genes encoding proteins of Ranvier domains or involved in
      myelination of Schwann cells are responsible for novel and severe human axoglial
      diseases. 

PMID- 24319101
TI  - Using data and quality monitoring to enhance maternity outcomes: a qualitative
      study of risk managers' perspectives.
AB  - INTRODUCTION: Risk management is a core part of healthcare practice, especially
      within maternity services, where litigation and societal costs are high. There
      has been little investigation into the experiences and opinions of those staff
      directly involved in risk management: lead obstetricians and specialist risk
      midwives, who are ideally placed to identify how current implementation of risk
      management strategies can be improved. METHODS: A qualitative study of consultant
      led maternity units in an English region. Semistructured interviews were
      conducted with the obstetric and midwifery risk management leads for each unit.
      We explored their approach to risk management, particularly their opinions
      regarding quality monitoring and related barriers/issues. Interviews were
      recorded, transcribed and thematically analysed. RESULTS: Twenty-seven staff from
      12/15 maternity units participated. Key issues identified included: concern for
      the accuracy and validity of their local data, potential difficulties related to
      data collation, the negative impact of external interference by national
      regulatory bodies on local clinical priorities, the influence of the local
      culture of the maternity unit on levels of engagement in the risk management
      process, and scepticism about the value of benchmarking of maternity units
      without adjustment for population characteristics. CONCLUSIONS: Local maternity
      risk managers may provide valuable, clinically relevant insights into current
      issues in clinical data monitoring. Improvements should focus on the accuracy and
      ease of data collation with a need for an agreed maternity indicators set,
      populated from validated databases, and not reliant on data collection systems
      that distract clinicians from patient activity and quality improvement. It is
      clear that working relationships between risk managers, their own clinical teams
      and external national bodies require improvement and alignment. Further
      discussion regarding benchmarking between maternity units is required prior to
      implementation. These findings are likely to be relevant to other clinical
      specialties.

PMID- 24319102
TI  - Quantitative flow cytometric identification of aberrant T cell clusters in
      erythrodermic cutaneous T cell lymphoma. Implications for staging and prognosis.
AB  - AIMS: Assessment of peripheral blood tumour burden for staging of cutaneous T
      cells lymphoma is most often accomplished by flow cytometry (FC) using various
      non-standarised strategies. We report the results of calculating absolute Sezary
      cell counts (SCCs) by FC, based on the identification of aberrant T cell clusters
      on a virtual 6-dimensional space and independently of the expected
      immunophenotype (6D-FC SCC). METHODS: 6D-FC SCCs were calculated on 65 peripheral
      blood specimens from 28 patients with erythrodermic cutaneous T cells lymphoma
      (stage III or IV). Comparisons were made with recommended FC strategies and
      correlations with overall mortality were studied. RESULTS: At first visit, 17 of
      28 patients (61%) had 6D-FC SCCs meeting current criteria for Stage IV disease
      (>=1000 SC/MUL); while only 2 patients (7%) met Stage IV criteria on other
      tissues. As defined by comprehensive staging using clinicomorphological criteria
      and 6D-FC SCCs, Stage IV disease identified a subgroup of patients with worse
      overall survival (p=0.0227). Residual non-aberrant CD4 T cells were markedly
      decreased in Stage IV disease (p=0.018). Among 65 specimens, discrepancies were
      observed between 6D-FC SCCs and usual FC thresholds for Stage IV disease, namely
      a CD4:CD8 ratio >=10:1 (9 discrepancies, 14%), and >=40% aberrant CD4 T cells (4
      discrepancies, 6%). Surprisingly, 8 cases (12%) from 6 patients exhibited two
      distinctively separate clusters of aberrant CD4 T cells with different CD7 and/or
      CD26 expression. CONCLUSIONS: Visual 6-dimensional identification of aberrant T
      cell clusters by FC allows for the calculation of clinically significant SCCs.
      Simplified gating strategies and relative quantitative values might underestimate
      the immunophenotypical complexity of Sezary cells.

PMID- 24319103
TI  - Proposed legislative change mandating retrospective release of identifying
      information: consultation with donors and Government response.
AB  - STUDY QUESTION: How do gamete donors who presumed they could remain anonymous
      respond to proposed legislation to retrospectively remove anonymity? SUMMARY
      ANSWER: A little more than half of the donors opposed the recommendation to
      introduce legislation to remove donor anonymity with retrospective effect. WHAT
      IS KNOWN ALREADY: An increasing proportion of parents disclose their origins to
      their donor-conceived children and growing numbers of donor-conceived adults are
      aware of how they were conceived. Research indicates that access to information
      about the donor is important to donor-conceived people. However, worldwide most
      donor-conceived people are unable to find any identifying information about the
      donor because of the practice of anonymous gamete donation. STUDY DESIGN, SIZE,
      DURATION: This study adopted a qualitative research model using semi-structured
      interviews with gamete donors that included open questions. Interviews with 42
      volunteers were conducted between December 2012 and February 2013.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Before 1998 gamete donors in Victoria,
      Australia, were able to remain anonymous. Pre-1998 donors were invited through an
      advertising campaign to be interviewed about their views on a recommendation that
      legislation mandating retrospective release of identifying information be
      introduced. MAIN RESULTS AND THE ROLE OF CHANCE: Donors were almost evenly split
      between those who supported and those who rejected the recommendation to
      introduce legislation to remove donor anonymity with retrospective effect. About
      half of the donors who rejected the recommendation suggested the compromise of
      persuading donors voluntarily to release information (whether identifying or non
      identifying) to donor-conceived people. These donors were themselves willing to
      supply information to their donor offspring. The findings of this study informed
      the Victorian Government's response to the proposed legislative change. While
      acknowledging donor-conceived people's right of access to information about their
      donors, the Government decided that identifying information should be released
      only with the consent of donors and that donors should be encouraged to allow
      themselves to be identifiable to their donor offspring. LIMITATIONS, REASONS FOR
      CAUTION: There is no way of knowing whether participants were representative of
      all pre-1998 donors. WIDER IMPLICATIONS OF THE FINDINGS: The balancing of donors'
      and donor-conceived people's rights requires utmost sensitivity. All over the
      world, increasing numbers of donor-conceived people are reaching adulthood; of
      those who are aware of their mode of conception, some are likely to have a strong
      wish to know the identity of their donors. Legislators and policy-makers in
      jurisdictions permitting anonymous gamete donations will need to respond when
      these desires are expressed, and may choose to be guided by the model of
      consultation described in this paper. STUDY FUNDING/COMPETING INTERESTS: The
      study was funded by the Victorian Department of Health. The authors have no
      conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 24319104
TI  - Ultrasonographic examination of rheumatoid arthritis patients who are free of
      physical synovitis: power Doppler subclinical synovitis is associated with bone
      erosion.
AB  - OBJECTIVE: The aim of this study was to investigate the characteristics of power
      Doppler (PD) subclinical synovitis in patients with RA who achieve clinical
      remission free from physical synovitis. METHODS: Twenty-nine RA patients were
      consecutively enrolled. All of the patients had achieved clinical remission
      [simplified disease activity index (SDAI) 3.3] for at least 6 months at the
      musculoskeletal ultrasound (MSKUS) examination. Additionally, none of the
      patients exhibited tender joints at 68 sites or swollen joints at 66 sites. MSKUS
      of bilateral wrist and finger joints, including the first to fifth MCP joints,
      the first IP joint and the second to fifth PIP joints, was performed and the
      findings obtained by grey scale (GS) and PD were graded on a semi-quantitative
      scale from 0 to 3. RESULTS: The median disease duration upon the introduction of
      DMARDs was 3 months and that at MSKUS examination was 21 months. The percentages
      of patients with PD synovitis in at least one joint were PD grade 1, 58.6%; PD
      grade 2, 31.0% and PD grade 3, 6.9%. The use of biological agents was low in
      patients with PD synovitis grade 2 (P < 0.05). The presence of US bone erosion
      was high by patient (P < 0.05) and by joint (P < 0.0001) with PD synovitis as
      compared with those without PD synovitis. However, no correlations were found
      between PD synovitis measures and serum biomarkers, including angiogenesis
      factors. CONCLUSION: PD subclinical synovitis correlates with several clinical
      characteristics, whereas conventional serum biomarkers are not useful for
      indicating the presence of subclinical PD synovitis.

PMID- 24319105
TI  - Correction and verification of AECL Bonner Sphere response matrix based on mono
      energetic neutron calibration performed at NPL.
AB  - The AECL Bonner Sphere Spectrometer (BSS) was taken to National Physical
      Laboratory (NPL) for calibration in mono-energetic neutron fields and bare
      (252)Cf neutron fields. The mono-energetic radiations were performed using ISO
      8529 prescribed neutron energies: 0.071, 0.144, 0.565, 1.2, 5 and 17 MeV. A
      central SP9 proportional counter was also evaluated at the NPL thermal neutron
      calibration facility in order to assess an effective pressure of (3)He inside the
      counter, i.e. number density of (3)He atoms. Based on these measurements and
      methods outlined by Thomas and Soochak, a new BSS response matrix was generated.
      The response matrix is then verified by unfolding spectra corresponding to
      various neutron fields. Those are NPL bare (252)Cf source, National Institute of
      Standards and Technology bare and heavy water moderated (252)Cf source and
      (241)AmBe calibration source located at National Research Council. A good
      agreement was observed with expected neutron fluence rates, as well as derived
      dosimetric quantities, such as International Commission on Radiological
      Protection-74 ambient dose equivalent. 

PMID- 24319106
TI  - Evaluation of natural radioactivity and its associated health hazard indices of a
      South Indian river.
AB  - The activity concentration of the natural radionuclides (226)Ra, (232)Th and
      (40)K was measured for sediment samples collected from thirty-three different
      locations along the Bharathapuzha river basin by using high-resolution gamma-ray
      spectrometry. The concentrations of the natural radionuclides were found to vary
      from location to location, and their mean values are 19.6, 82.87 and 19.44%
      higher than the worldwide mean values of (226)Ra, (232)Th and (40)K,
      respectively. The value of (232)Th was found to be higher than that of (226)Ra in
      82% of the samples collected for this study. The calculated values of indoor
      gamma dose rate (DIN) ranged between 89.55 and 194.24 nGy h(-1), and the overall
      mean value is 63.2% higher than the recommended safe and criterion limit by
      UNSCEAR. The internal and external hazard indices (H(in) and H(ex)), the
      representative gamma index and alpha index (I(gamma) and I(alpha)), the annual
      gonad dose equivalent (AGDE) and the excess lifetime cancer risk (ELCR) were also
      calculated and compared with the international recommended values. Multivariate
      statistical analyses were also carried out to determine the relation between the
      natural radionuclides and various radiological parameters.

PMID- 24319109
TI  - Differential induction of autophagy by mTOR is associated with abnormal apoptosis
      in ovarian endometriotic cysts.
AB  - Mammalian target of rapamycin (mTOR) is known to be a major negative regulator of
      autophagy. Recent studies have shown that mTOR activity is abnormally increased
      in endometriotic lesions. In endometriosis, abnormal mTOR activity may contribute
      to the alteration of endometrial cell autophagy, which may affect apoptosis
      because endometrial cell autophagy is directly involved in the regulation of
      apoptosis. To test this hypothesis, we investigated whether endometrial cell
      autophagy is altered by aberrant mTOR activity and is associated with apoptosis
      in ovarian endometriotic cysts. Our results show that endometrial cell autophagy
      induction was increased by mTOR inhibition as the menstrual cycle progresses in
      the normal endometrium, and that it is correlated with apoptosis. However, in
      endometriotic tissues from ovarian endometriotic cysts, autophagy, mTOR activity
      and apoptosis were constant throughout the menstrual cycle, suggesting that a
      constant level of autophagy is maintained by disinhibition of mTOR activity
      during the menstrual cycle in endometriotic tissues and is related to decreased
      apoptosis. Indeed, compared with normal endometrium, increased mTOR activity
      during the secretory phase in endometriotic tissues inhibited autophagy and
      apoptosis induction. In addition, to determine the direct effect of autophagy
      induction mediated by mTOR on endometriotic cell apoptosis, endometriotic cells
      were treated with rapamacin (mTOR inhibitor) with and without 3-methyladenine (3
      MA, autophagy inhibitor). Although rapamycin treatment induced autophagy and led
      to apoptosis promotion, the pro-apoptotic effect of rapamycin was reversed by the
      addition of 3-MA, suggesting that mTOR inhibition promotes endometriotic cell
      apoptosis via autophagy induction. In conclusion, our results suggest that
      aberrant mTOR activity in ovarian endometriotic cysts leads to alteration of
      endometrial cell autophagy, which is associated with abnormal apoptosis. 

PMID- 24319110
TI  - Sidedness of carbamazepine accessibility to voltage-gated sodium channels.
AB  - Voltage-gated sodium channels are inhibited by many local anesthetics,
      antiarrhythmics, and antiepileptic drugs. The local anesthetic lidocaine appears
      to be able to access its binding site in the sodium channel only from the
      membrane phase or from the internal face of the channel. In contrast, the
      antiepileptic drug carbamazepine was found to inhibit voltage-gated sodium
      channels only with external, but not internal, application, implying a major
      difference. We investigated this point using both whole-cell and inside-out patch
      recordings from human Na(v)1.7 channels in a stable cell line. In the whole-cell
      configuration, carbamazepine inhibited sodium current within seconds when applied
      externally, but had little or no effect when applied internally for up to 15
      minutes, confirming previous results. However, carbamazepine inhibited sodium
      channels effectively and rapidly when applied to the internal face of the
      membrane using inside-out patch recording. We found that lidocaine also has
      little or no effect when applied intracellularly in whole-cell recording, but
      blocks effectively and rapidly when applied to the internal surface using inside
      out patches. In contrast, the cationic lidocaine derivative QX-314 (N-ethyl
      lidocaine) blocks effectively when applied internally with whole-cell dialysis,
      as well as when applied to inside-out patches. We conclude that carbamazepine and
      lidocaine access the sodium channel in similar ways and hypothesize that their
      lack of effect with internal dialysis in whole-cell recording reflects rapid exit
      through membrane near the pipette recording site. This effect likely limits the
      ability of any compound with significant membrane permeability to be applied
      intracellularly by whole-cell dialysis.

PMID- 24319111
TI  - Regulation of beta2-adrenergic receptor function by conformationally selective
      single-domain intrabodies.
AB  - The biologic activity induced by ligand binding to orthosteric or allosteric
      sites on a G protein-coupled receptor (GPCR) is mediated by stabilization of
      specific receptor conformations. In the case of the beta2 adrenergic receptor,
      these ligands are generally small-molecule agonists or antagonists. However, a
      monomeric single-domain antibody (nanobody) from the Camelid family was recently
      found to allosterically bind and stabilize an active conformation of the beta2
      adrenergic receptor (beta2AR). Here, we set out to study the functional
      interaction of 18 related nanobodies with the beta2AR to investigate their roles
      as novel tools for studying GPCR biology. Our studies revealed several sequence
      related nanobody families with preferences for active (agonist-occupied) or
      inactive (antagonist-occupied) receptors. Flow cytometry analysis indicates that
      all nanobodies bind to epitopes displayed on the intracellular receptor surface;
      therefore, we transiently expressed them intracellularly as "intrabodies" to test
      their effects on beta2AR-dependent signaling. Conformational specificity was
      preserved after intrabody conversion as demonstrated by the ability for the
      intracellularly expressed nanobodies to selectively bind agonist- or antagonist
      occupied receptors. When expressed as intrabodies, they inhibited G protein
      activation (cyclic AMP accumulation), G protein-coupled receptor kinase (GRK)
      mediated receptor phosphorylation, beta-arrestin recruitment, and receptor
      internalization to varying extents. These functional effects were likely due to
      either steric blockade of downstream effector (Gs, beta-arrestin, GRK)
      interactions or stabilization of specific receptor conformations which do not
      support effector coupling. Together, these findings strongly implicate nanobody
      derived intrabodies as novel tools to study GPCR biology. 

PMID- 24319112
TI  - Novel paradigms for dialysis vascular access: Introduction.

PMID- 24319113
TI  - DATABASE, The Journal of Biological Databases and Curation, is now the official
      journal of the International Society for Biocuration.

PMID- 24319114
TI  - FABP4 attenuates PPARgamma and adipogenesis and is inversely correlated with
      PPARgamma in adipose tissues.
AB  - Fatty acid binding protein 4 (FABP4, also known as aP2) is a cytoplasmic fatty
      acid chaperone expressed primarily in adipocytes and myeloid cells and implicated
      in the development of insulin resistance and atherosclerosis. Here we demonstrate
      that FABP4 triggers the ubiquitination and subsequent proteasomal degradation of
      peroxisome proliferator-activated receptor gamma (PPARgamma), a master regulator
      of adipogenesis and insulin responsiveness. Importantly, FABP4-null mouse
      preadipocytes as well as macrophages exhibited increased expression of PPARgamma,
      and complementation of FABP4 in the macrophages reversed the increase in FABP4
      expression. The FABP4-null preadipocytes exhibited a remarkably enhanced
      adipogenesis compared with wild-type cells, indicating that FABP4 regulates
      adipogenesis by downregulating PPARgamma. We found that the FABP4 level was
      higher and PPARgamma level was lower in human visceral fat and mouse epididymal
      fat compared with their subcutaneous fat. Furthermore, FABP4 was higher in the
      adipose tissues of obese diabetic individuals compared with healthy ones.
      Suppression of PPARgamma by FABP4 in visceral fat may explain the reported role
      of FABP4 in the development of obesity-related morbidities, including insulin
      resistance, diabetes, and atherosclerosis. 

PMID- 24319115
TI  - Pronounced reduction of cutaneous Langerhans cell density in recently diagnosed
      type 2 diabetes.
AB  - Immune-mediated processes have been implicated in the pathogenesis of diabetic
      polyneuropathy. Langerhans cells (LCs) are the sole dendritic cell type located
      in the healthy epidermis and exert tolerogenic immune functions. We aimed to
      determine whether alterations in cutaneous LC density and intraepidermal nerve
      fiber density (IENFD) are present in patients with recently diagnosed type 2
      diabetes. Skin biopsy specimens from the distal leg from 96 type 2 diabetic
      patients and 75 healthy control subjects were used for quantification of LC
      density and IENFD. LCs and IENFs were labeled using immunohistochemistry. Nerve
      conduction studies, quantitative sensory testing, and neurological examination
      were used to assess peripheral nerve function. LC density was markedly reduced in
      the diabetic group compared with the control group, but did not correlate with
      reduced IENFD or peripheral nerve function. Multivariate linear regression
      analysis revealed a strong association between LC density and whole-body insulin
      sensitivity in women but not in men with diabetes. Prospective studies should
      establish whether the pronounced reduction of cutaneous LCs detected in recently
      diagnosed type 2 diabetes could promote a cutaneous immunogenic imbalance toward
      inflammation predisposing to polyneuropathy and foot ulcers. 

PMID- 24319116
TI  - Tracking the dynamics of the social brain: ERP approaches for social cognitive
      and affective neuroscience.
AB  - Event-related potential (ERP) approaches to social cognitive and affective
      neuroscience (SCAN) are not as widely used as other neuroimaging techniques, yet
      they offer several unique advantages. In particular, the high temporal resolution
      of ERP measures of neural activity make them ideally suited for studying the
      dynamic interplay of rapidly unfolding cognitive and affective processes. In this
      article, we highlight the utility of ERP methods for scientists investigating
      questions of SCAN. We begin with a brief description of the physiological basis
      of ERPs and discussion of methodological practices. We then discuss how ERPs may
      be used to address a range of questions concerning social perception, social
      cognition, attitudes, affect and self-regulation, with examples of research that
      has used the ERP approach to contribute important theoretical advances in these
      areas. Whether used alone or in combination with other techniques, the ERP is an
      indispensable part of the social and affective neuroscientist's methodological
      toolkit. 

PMID- 24319117
TI  - Self-disturbances in schizophrenia: history, phenomenology, and relevant findings
      from research on metacognition.
AB  - With a tradition of examining self-disturbances (Ichstorungen) in schizophrenia,
      phenomenological psychiatry studies the person's subjective experience without
      imposing theoretical agenda on what is reported. Although this tradition offers
      promising interface with current neurobiological models of schizophrenia, both
      the concept of Ichstorung and its history are not well understood. In this
      article, we discuss the meaning of Ichstorung, the role it played in the
      development of the concept of schizophrenia, and recent research on metacognition
      that allows for the quantitative study of the link between self-disturbance and
      outcome in schizophrenia. Phenomenological psychiatrists such as Blankenburg,
      Binswanger, and Conrad interpreted the Ichstorung as disturbed relationship to
      self and others, thus challenging recent efforts to interpret self-disturbance as
      diminished pure passive self-affection, which putatively "explains" schizophrenia
      and its various symptoms. Narrative is a reflective, embodied process, which
      requires a dynamic shifting of perspectives which, when compromised, may reflect
      disrupted binding of the components of self-experience. The Metacognition
      Assessment Scale-abbreviated as MAS-A-suggests that persons with schizophrenia
      tend to produce narratives with reductions in the binding processes required to
      produce an integrated, embodied self within narrated life stories, and in
      interactive relationships with others. 

PMID- 24319118
TI  - Boosting the power of schizophrenia genetics by leveraging new statistical tools.
AB  - Genome-wide association studies (GWAS) have identified a large number of gene
      variants associated with schizophrenia, but these variants explain only a small
      portion of the heritability. It is becoming increasingly clear that schizophrenia
      is influenced by many genes, most of which have effects too small to be
      identified using traditional GWAS statistical methods. By applying recently
      developed Empirical Bayes statistical approaches, we have demonstrated that
      functional genic elements show differential contribution to phenotypic variance,
      with some elements (regulatory regions and exons) showing strong enrichment for
      association with schizophrenia. Applying related methods, we also showed abundant
      genetic overlap (pleiotropy) between schizophrenia and other phenotypes,
      including bipolar disorder, cardiovascular disease risk factors, and multiple
      sclerosis. We estimated the number of gene variants with effects in schizophrenia
      and bipolar disorder to be approximately 1.2%. By applying our novel statistical
      framework, we dramatically improved gene discovery and detected a large number of
      new gene loci associated with schizophrenia that have not yet been identified
      with standard GWAS methods. Utilizing independent schizophrenia substudies, we
      showed that these new loci have high replication rates in de novo samples,
      indicating that they likely represent true schizophrenia risk genes. The new
      statistical tools provide a powerful approach for uncovering more of the missing
      heritability of schizophrenia and other complex disorders. In conclusion, the
      highly polygenic architecture of schizophrenia strongly suggests the utility of
      research approaches that recognize schizophrenia neuropathology as a complex
      dynamic system, with many small gene effects integrated in functional networks. 

PMID- 24319119
TI  - A psychoeducational program to restore hypoglycemia awareness: the DAFNE-HART
      pilot study.
AB  - OBJECTIVE: To develop and pilot a novel intervention addressing motivational and
      cognitive barriers to avoiding hypoglycemia in people with type 1 diabetes and
      persistent impaired awareness of hypoglycemia (IAH) despite training in flexible
      insulin therapy. RESEARCH DESIGN AND METHODS: A 6-week intervention using
      motivational interviewing and cognitive behavioral techniques was designed.
      Diabetes educators were trained and supported in its delivery to 23 people with
      IAH (Gold score >=4). RESULTS: Twelve months postcourse, hypoglycemia awareness
      had improved (P < 0.001). Median (range) rates of severe hypoglycemia (SH) fell
      from 3 (0-104) to 0 (0-3) per person per year (P < 0.0001) and moderate from 14
      (0-100) to 0 (0-18) per person per 6 weeks (P < 0.001). Worry and behavior around
      hyperglycemia improved. HbA1c was unchanged. CONCLUSIONS: A pilot intervention
      targeting motivation and cognitions around hypoglycemia engaged patients with
      resistant IAH and recurrent SH and was associated with significant improvement,
      supporting the hypothesis that these factors underpin problematic hypoglycemia.

PMID- 24319120
TI  - Quantitative estimation of insulin sensitivity in type 1 diabetic subjects
      wearing a sensor-augmented insulin pump.
AB  - OBJECTIVE: The goal was to develop a new index of insulin sensitivity in patients
      with type 1 diabetes estimated from continuous glucose monitoring (CGM) and
      subcutaneous insulin delivery data under carefully controlled conditions.
      RESEARCH DESIGN AND METHODS: The database consists of 12 subjects with type 1
      diabetes, studied during breakfast, lunch, and dinner, in a clinical research
      unit, wearing both subcutaneous insulin pump and CGM device. Frequent blood
      samples were drawn for measurements of plasma glucose and insulin concentrations
      in order to estimate insulin sensitivity with the oral minimal model (SI(MM)).
      The new index of insulin sensitivity (SI(SP)) was calculated with a simple
      algebraic formula for each meal, using only CGM and insulin pump data and
      compared with SI(MM). RESULTS: SI(SP) was well correlated with SI(MM) (r = 0.825;
      P < 10(-8)), and diurnal pattern was also similar to SI(MM). CONCLUSIONS: A novel
      method for estimating insulin sensitivity in subjects with type 1 diabetes on
      sensor-augmented insulin pump therapy has been presented. This new index
      correlates well with the reference oral minimal model estimate of insulin
      sensitivity. The knowledge of patient-specific insulin sensitivity and its
      diurnal variation can help in optimizing insulin therapy in type 1 diabetes and
      could also inform next-generation closed-loop control systems.

PMID- 24319121
TI  - Scaling up diabetes prevention in Victoria, Australia: policy development,
      implementation, and evaluation.
AB  - OBJECTIVE The Australian lifestyle intervention program Life! is only the second
      reported, large-scale diabetes prevention program. This article describes the
      genesis and the successful establishment of Life! and its key outcomes for
      participants and implementation. RESEARCH DESIGN AND METHODS Life!, a behavior
      change intervention, comprises six group sessions over 8 months. The Victorian
      Department of Health funded Diabetes Australia-Victoria to implement the program.
      Experience of the Greater Green Triangle diabetes prevention implementation trial
      was used for intervention design, workforce development, training, and
      infrastructure. Clinical and anthropometric data from participants, used for
      program evaluation, were recorded on a central database. RESULTS Life! has a
      statewide workforce of 302 trained facilitators within 137 organizations. Over
      29,000 Victorians showed interest in Life!, and 15,000 individuals have been
      referred to the program. In total, 8,412 participants commenced a Life! program
      between October 2007 and June 2011, and 37% of the original participants
      completed the 8-month program. Participants completing sessions 1 to 5 lost an
      average of 1.4 kg weight (P < 0.001) and waist circumference of 2.5 cm (P <
      0.001). Those completing six sessions lost an average of 2.4 kg weight (P <
      0.001) and waist circumference of 3.8 cm (P < 0.001). The weight loss of 2.4 kg
      represents 2.7% of participants' starting body weight. CONCLUSIONS The impact of
      Life! is attributable to applying available evidence for the system's design of
      the intervention and collaboration between policy makers, implementers, and
      evaluators using the principles of continuous quality improvement to support
      successful, large-scale recruitment and implementation. 

PMID- 24319122
TI  - Proliferative retinopathy in type 1 diabetes is associated with cerebral
      microbleeds, which is part of generalized microangiopathy.
AB  - OBJECTIVE We investigated whether proliferative diabetic retinopathy in type 1
      diabetic patients can be generalized to cerebral small vessel disease and whether
      it is associated with impaired peripheral microvascular function. RESEARCH DESIGN
      AND METHODS Thirty-three patients with proliferative diabetic retinopathy (PDR+),
      34 patients without proliferative diabetic retinopathy, and 33 controls underwent
      magnetic resonance imaging to assess cerebral microangiopathy (cerebral
      microbleeds) and ischemic damage (white matter hyperintensities and lacunes).
      Peripheral microvascular function, i.e., skin capillary density and capillary
      recruitment, was assessed by capillary microscopy. RESULTS Cerebral microbleeds,
      but not ischemic damage, were more prevalent in PDR+ patients versus the other
      groups (P < 0.05). A trend was found across groups for the lowest baseline
      capillary density in PDR+ patients (P for trend = 0.05). In individuals with
      microbleeds, capillary recruitment was impaired compared with those without
      microbleeds (P = 0.04). CONCLUSIONS In PDR+ patients, cerebral microbleed
      prevalence was higher and seems part of generalized microangiopathy that may
      affect the skin and the brain. 

PMID- 24319124
TI  - Alpha-amylase inhibitor, CS-1036 binds to serum amylase in a concentration
      dependent and saturable manner.
AB  - (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-beta-D
      glucopyranosyl)-alpha-D-glucopyranoside (CS-1036), which is an alpha-amylase
      inhibitor, exhibited biphasic and sustained elimination with a long t1/2 (18.4
      30.0 hours) in rats and monkeys, but exhibited a short t1/2 (3.7-7.9 hours) in
      humans. To clarify the species differences in the t1/2, the plasma protein
      binding of CS-1036 was evaluated by ultrafiltration. A concentration-dependent
      and saturable plasma protein binding of CS-1036 was observed in rats and monkeys
      with the dissociation rate constant (KD) of 8.95 and 27.2 nM, and maximal binding
      capacity (Bmax) of 52.8 and 22.1 nM, respectively. By the assessments of the
      recombinant amylase and immunoprecipitation, the major binding protein of CS-1036
      in rats was identified as salivary amylase (KD 5.64 nM). CS-1036 also showed
      concentration-dependent and saturable binding to human salivary and pancreatic
      amylase, with similar binding affinity in rats. However, the protein binding of
      CS-1036 was constant in human plasma (<=10.2%) due to the lower serum amylase
      level compared with rats and monkeys. From the calculation of the unbound
      fraction (fu) in plasma based on in vitro KD and Bmax, the dose-dependent
      increase in fu after oral administration is speculated to lead to a dose
      dependent increase in total body clearance and a high area under the curve/dose
      at lower doses, such as 0.3 mg/kg in rats. 

PMID- 24319123
TI  - Alterations in white matter structure in young children with type 1 diabetes.
AB  - OBJECTIVE: To investigate whether type 1 diabetes affects white matter (WM)
      structure in a large sample of young children. RESEARCH DESIGN AND METHODS:
      Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched
      nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance
      imaging scans in this multisite neuroimaging study. Participants with type 1
      diabetes were assessed for HbA1c history and lifetime adverse events, and glucose
      levels were monitored using a continuous glucose monitor (CGM) device and
      standardized measures of cognition. RESULTS: Between-group analysis showed that
      children with type 1 diabetes had significantly reduced axial diffusivity (AD) in
      widespread brain regions compared with control subjects. Within the type 1
      diabetes group, earlier onset of diabetes was associated with increased radial
      diffusivity (RD) and longer duration was associated with reduced AD, reduced RD,
      and increased fractional anisotropy (FA). In addition, HbA1c values were
      significantly negatively associated with FA values and were positively associated
      with RD values in widespread brain regions. Significant associations of AD, RD,
      and FA were found for CGM measures of hyperglycemia and glucose variability but
      not for hypoglycemia. Finally, we observed a significant association between WM
      structure and cognitive ability in children with type 1 diabetes but not in
      control subjects. CONCLUSIONS: These results suggest vulnerability of the
      developing brain in young children to effects of type 1 diabetes associated with
      chronic hyperglycemia and glucose variability.

PMID- 24319126
TI  - Knowing where we're going in assessment.

PMID- 24319125
TI  - New software for cervical vertebral geometry assessment and its relationship to
      skeletal maturation--a pilot study.
AB  - OBJECTIVES: In the present study, we developed new software for quantitative
      analysis of cervical vertebrae maturation, and we evaluated its applicability
      through a multinomial logistic regression model (MLRM). METHODS: Digitized images
      of the bodies of the second (C2), third (C3) and fourth (C4) cervical vertebrae
      were analysed in cephalometric radiographs of 236 subjects (116 boys and 120
      girls) by using a software developed for digitized vertebrae analysis. The sample
      was initially distributed into 11 categories according to the Fishman's skeletal
      maturity indicators and were then grouped into four stages for quantitative
      cervical maturational changes (QCMC) analysis (QCMC I, II, III and IV). Seven
      variables of interest were measured and analysed to identify morphologic
      alterations of the vertebral bodies in each QCMC category. RESULTS: Statistically
      significant differences (p < 0.05) were observed among all QCMC categories for
      the variables analysed. The MLRM used to calculate the probability that an
      individual belonged to each of the four cervical vertebrae maturation categories
      was constructed by taking into account gender, chronological age and four
      variables determined by digitized vertebrae analysis (Ang_C3, MP_C3, MP_C4 and
      SP_C4). The MLRM presented a predictability of 81.4%. The weighted kappa test
      showed almost perfect agreement (kappa = 0.832) between the categories defined
      initially by the method of Fishman and those allocated by the MLRM. CONCLUSIONS:
      Significant alterations in the morphologies of the C2, C3 and C4 vertebral bodies
      that were analysed through the digitized vertebrae analysis software occur during
      the different stages of skeletal maturation. The model that combines the four
      parameters measured on the vertebral bodies, the age and the gender showed an
      excellent prediction.

PMID- 24319127
TI  - Development and implementation of online National Board Dental Examination Review
      Courses.
AB  - Failure on the National Board Dental Examination (NBDE) Parts I and II has
      troubling consequences for dental students, faculty members, and school
      administrators. Since the NBDE is a high-stakes exam for all involved, it is
      important to determine effective strategies to help students prepare. The purpose
      of this article is to describe the development and implementation of online NBDE
      Parts I and II Review Courses by the faculty and administration at the University
      of Missouri-Kansas City School of Dentistry. The courses are taught by faculty
      members who are content experts. By utilizing distance technology, students in
      any geographic location can review the material at the time, place, and pace that
      are most convenient. Early outcomes show that 592 students from thirty-two states
      have participated in the courses since they were first offered in 2010-11. In
      post-course evaluations, students report that participation in the courses
      encouraged them to spend more time preparing for the exam and that the associated
      PowerPoint slides/handouts provided structure for their review. The literature
      suggests that multiple modalities are most effective in preparing for the NBDE.
      These online review courses can serve as a beneficial component of a student's
      preparation regimen. 

PMID- 24319128
TI  - NBDE Part II practice analyses: an overview.
AB  - The Standards for Educational and Psychological Testing emphasize the importance
      of documenting and describing the procedures followed in developing valid test
      content. As a result, the Joint Commission on National Dental Examinations, the
      testing agency responsible for administering the National Board Dental
      Examination Part I and Part II, routinely communicates information about the
      validity of Part II to dental schools and other communities of interest. Since
      2000, the content of Part II has been validated through the use of three practice
      analyses. This article provides an overview of these practice analyses, including
      procedures and findings. In general, the findings confirm that the content of
      Part II is valid in determining the qualifications of individuals seeking dental
      licensure. 

PMID- 24319129
TI  - Reporting school data on the dental licensure examination.
AB  - Beginning in 2012, candidate performance on the National Board Dental Examination
      (NBDE) has been reported as pass/fail, and only the failing candidates receive
      numerical scores for remediation purposes. The Joint Commission on National
      Dental Examinations recognizes that the numerical scores have been important
      information to dental schools for curriculum evaluation and that the pass/fail
      reports do not provide meaningful information to the schools. This article
      describes the process of evaluating and validating a new model for reporting
      standardized school-level performance data on the NBDE. Under this new model,
      schools are able to monitor the overall performance of their students compared to
      a national cohort. 

PMID- 24319130
TI  - Constructing licensure exams: a reliability study of case-based questions on the
      National Board Dental Hygiene Examination.
AB  - Patient cases with associated questions are a method for increasing the clinical
      relevance of licensure exams. This study used generalizability theory to assess
      changes in score reliability when the number of questions per case varied in the
      National Board Dental Hygiene Examination (NBDHE). The experimental design
      maintained the same total number of case-based items, while varying the number of
      cases and items within cases to assess changes in score reliability. Using
      generalizability theory, the amounts of error variance within cases and between
      cases on the NBDHE were assessed. Impact on score reliability (generalizability)
      was computed. The data were from the responses of 4,528 candidates who took the
      paper-pencil version of the NBDHE in spring 2009. Results showed that the minimum
      value of generalizability occurred when fourteen cases with ten items each were
      used in the examination. The maximum value of generalizability occurred when
      fifty cases with three items each were used in the examination. The research
      findings support the development of more cases with fewer items per case on the
      NBDHE in order to enhance test score reliability and validity. Practical
      constraints should be considered if more cases with fewer items per case are
      developed for future examinations. 

PMID- 24319131
TI  - Improving multiple-choice questions to better assess dental student knowledge:
      distractor utilization in oral and maxillofacial pathology course examinations.
AB  - How many incorrect response options (known as distractors) to use in multiple
      choice questions has been the source of considerable debate in the assessment
      literature, especially relative to influence on the likelihood of students'
      guessing the correct answer. This study compared distractor use by second-year
      dental students in three successive oral and maxillofacial pathology classes that
      had three different examination question formats and scoring resulting in
      different levels of academic performance. One class was given all multiple-choice
      questions; the two other were given half multiple-choice questions, with and
      without formula scoring, and half un-cued short-answer questions. Use by at least
      1 percent of the students was found to better identify functioning distractors
      than higher cutoffs. The average number of functioning distractors differed among
      the three classes and did not always correspond to differences in class scores.
      Increased numbers of functioning distractors were associated with higher question
      discrimination and greater question difficulty. Fewer functioning distractors
      fostered more effective student guessing and overestimation of academic
      achievement. Appropriate identification of functioning distractors is essential
      for improving examination quality and better estimating actual student knowledge
      through retrospective use of formula scoring, where the amount subtracted for
      incorrect answers is based on the harmonic mean number of functioning
      distractors. 

PMID- 24319132
TI  - Complementary and alternative medicine in predoctoral dental curricula: an
      exploratory survey of U.S. dental schools.
AB  - The purpose of this study was to identify the prevalence of complementary and
      alternative medicine (CAM) education in U.S. dental schools. A survey was
      administered via e-mail to each U.S. dental school's academic dean, and data were
      collected from respondents in a fillable PDF form submitted electronically to the
      study investigators. The survey asked respondents whether CAM was taught at the
      institution; if the response was yes, information was requested regarding the CAM
      therapies included, credentials of the instructor, number of hours taught, reason
      for teaching CAM, and format in which CAM was taught. Of the sixty dental schools
      contacted, twenty-two responded to the survey (37 percent response rate). Of
      these respondents, ten (45.5 percent) reported offering instruction in CAM as
      part of their predoctoral curricula. Herb/drug interactions were found to be
      taught with more frequency than any other CAM topic (in six out of the ten
      institutions). Limitations of the study are discussed, and suggestions for future
      studies are made. 

PMID- 24319133
TI  - Who succeeds at dental school? Factors predicting students' academic performance
      in a dental school in republic of Korea.
AB  - The purpose of this study was to examine what cognitive and non-cognitive factors
      were responsible for predicting the academic performance of dental students in a
      dental school in the Republic of Korea. This school is one of those in Korea that
      now require applicants to have a bachelor's degree. In terms of cognitive
      factors, students' undergraduate grade point average (GPA) and Dental Education
      Eligibility Test (DEET) scores were used, while surveys were conducted to
      evaluate four non-cognitive measures: locus of control, self-esteem, self
      directed learning, and interpersonal skills. A total of 353 students
      matriculating at Seoul National University School of Dentistry in 2005, 2006,
      2007, and 2008 consented to the collection of records and completed the surveys.
      The main finding was that applicants who scored higher on internal locus of
      control and self-efficacy were more likely to be academically successful dental
      students. Self-directed learning was significantly associated with students
      ranked in the top 50 percent in cumulative GPA. However, students' interpersonal
      skills were negatively related to their academic performance. In particular,
      students' lack of achievement could be predicted by monitoring their first-year
      GPA. Therefore, the identification of those factors to predict dental school
      performance has implications for the dental curriculum and effective pedagogy in
      dental education. 

PMID- 24319134
TI  - Dental students' perceptions of the use of digital microscopy as part of an oral
      pathology curriculum.
AB  - Recent technological advances have allowed the computer to be turned into a
      microscope and therefore entailed a shift from light microscopy to digital
      microscopy (DM). Recent studies have shown that DM is gaining popularity in
      multiple academic fields, including dentistry. The aim of this study was to
      assess the perceptions of Midwestern University College of Dental Medicine
      Illinois second-year dental students of the use of DM as a component of the
      institution's oral and maxillofacial pathology curriculum. After 129 students
      utilized DM in an oral and maxillofacial pathology course, they were asked to
      complete a voluntary survey regarding their perceptions of the use of DM. A total
      of 123 students responded, for a response rate of 95 percent; 112 of these were
      included in the final analysis. Nearly all the respondents (92 percent) favored
      DM over light microscopy. Almost all (98 percent) agreed that the digital
      microscope enhanced their learning, and 97 percent agreed that it allowed for
      greater collaboration among peers. These findings support the implementation of
      DM as the primary teaching methodology in the field of oral and maxillofacial
      pathology. 

PMID- 24319135
TI  - Seeing through the dentist's eyes: video-based clinical demonstrations in
      preclinical dental training.
AB  - The clinical demonstration is an established way of bridging the disciplinary
      content in preclinical and clinical courses. In dentistry, however, clinical
      demonstrations have often been perceived as less rewarding due to the restricted
      visual access to the details of the treatment. This study investigated a course
      in endodontics at the University of Gothenburg, Sweden, in which traditional
      clinical demonstrations were replaced by instructor-led seminars that enabled
      students to follow and discuss broadcasted root canal treatments. Two cameras
      provided overviews of the operating room, whereas a third camera attached to a
      surgical microscope offered a magnified view of procedures carried out in the
      inner parts of teeth. The hypothesis was that this arrangement would increase the
      students' sense of the clinical relevance of basic scientific knowledge. Two
      focus group interviews were designed to explore the students' perceptions of this
      change. The students expressed that the video-based seminars offered ample
      opportunities to integrate theoretical and clinical understanding. The major
      reasons were that the visualization displayed procedures on a sufficiently
      detailed level; instructors demonstrated clinical reasoning in situ and provided
      the context necessary for understanding procedures; and the interactive format
      encouraged discussions on the generalizability of knowledge beyond the specific
      case. 

PMID- 24319136
TI  - Assessment of the efficacy of second life, a virtual learning environment, in
      dental education.
AB  - This study assessed the efficacy of Second Life (SL) in delivering lectures and
      demonstrating clinical procedures. Sixteen students in a dental school in
      Alexandria, Egypt, volunteered to participate in SL to learn about topical
      fluoride through lectures and YouTube videos demonstrating the application of
      fluoride gel. This was followed by face to face (F2F) sessions about pits and
      fissures sealant including lectures and F2F demonstration. Knowledge improvement
      was assessed by pre- and posttests; practical skills were assessed by a
      checklist; and percent scores were calculated. The relation between these scores
      and some background variables was assessed. Students' satisfaction with and
      perceptions of SL were also assessed. Knowledge improved significantly after both
      SL and F2F experiences (p<0.0001 for both). There were no significant differences
      between SL and F2F in knowledge improvement or skills percent scores (p=0.16 and
      0.26, respectively). Knowledge improvement was significantly related to previous
      experience with SL and previous year grade (p=0.02 and 0.007, respectively) but
      not to gender. Practical skills scores were not related to any of these three
      variables. Satisfaction with SL experience was high and not affected by any of
      the three variables, and the experience was perceived positively. This study
      suggests that SL can complement traditional F2F teaching, especially for
      underachieving students and in higher education institutions with problems of
      increasing numbers of students and limited space. 

PMID- 24319137
TI  - Students' clinical learning in an emerging dental school: an investigation in
      international collaboration between Michigan and Ghana.
AB  - The dearth of dental faculty members is a widely known problem that is
      exacerbated in countries that are attempting to begin dental education programs.
      This collaboration between Kwame Nkrumah University of Science and Technology and
      the University of Michigan investigated if dental students who have just started
      their clinical dental education can learn the knowledge and skills required for
      identifying and restoring cavitated caries lesions through compact course
      delivery. There were three instructional blocks: 1) didactic seminar; 2) seminar,
      simulated hands-on skills instruction, and clinical observation/assisting with
      treatment of schoolchildren; and 3) seminar, simulated skills training, and
      application to schoolchildren. Each dental student completed a questionnaire
      measuring knowledge and perceptions of knowledge, experience, and confidence at
      five points in time. The dental students' knowledge increased significantly as
      well as their perceived knowledge, experience, and confidence (p<0.0001). In
      general, the students showed proficiency in delivering simple treatments. The
      project showed that an integrated compact course delivery model may assist
      emerging dental schools to cope with the challenging shortage of resident faculty
      members. 

PMID- 24319138
TI  - Motivational interviewing in dental hygiene education: curriculum modification
      and evaluation.
AB  - Motivational interviewing (MI) is a person-centered, goal-directed method of
      communication for eliciting and strengthening intrinsic motivation for behavior
      change. Originally developed in the field of addiction therapy, MI has been
      increasing applied in the health professions with a growing body of successful
      outcomes for tobacco cessation and diabetic control, which can significantly
      impact oral health. MI has shown preliminary value for impacting oral behaviors
      that reduce early childhood caries, plaque, and gingival inflammation. While the
      training in and use of MI by oral health providers is emerging, full integration
      into dental and dental hygiene curricula has yet to be explored. Therefore, the
      purpose of this project was to evaluate the full implementation of MI in the
      classroom and clinic of a dental hygiene curriculum. 

PMID- 24319139
TI  - Reducing oral and maxillofacial surgery resident risk exposure: lessons from
      graduate medical education reform.
AB  - It is estimated that, in the United States, more than 40,000 patients are injured
      each day because of preventable medical errors. Although numerous studies examine
      the causes of medical trainee errors and efforts to mitigate patient injuries in
      this population, little research exists on adverse events experienced by oral and
      maxillofacial surgery (OMFS) residents or strategies to improve patient safety
      awareness in OMFS residency programs. The authors conducted a retrospective
      literature review of contemporary studies on medical trainees' reported risk
      exposure and the impact of integrating evidence-based patient safety training
      into residency curricula. A review of the literature suggests that OMFS residents
      face similar risks as medical trainees in medical, surgical, and anesthesia
      residency programs and may benefit from integrating competency-based safety
      training in the OMFS residency curriculum. OMFS trainees face particular
      challenges when transitioning from dental student to surgical resident,
      particularly related to their limited clinical exposure to high-reliability
      organizations, which may place them at higher risk than other medical trainees.
      OMFS educators should establish resident competence in patient safety principles
      and system improvement strategies throughout the training period. 

PMID- 24319142
TI  - Expanding the catalog of cas genes with metagenomes.
AB  - The CRISPR (clusters of regularly interspaced short palindromic repeats)-Cas
      adaptive immune system is an important defense system in bacteria, providing
      targeted defense against invasions of foreign nucleic acids. CRISPR-Cas systems
      consist of CRISPR loci and cas (CRISPR-associated) genes: sequence segments of
      invaders are incorporated into host genomes at CRISPR loci to generate
      specificity, while adjacent cas genes encode proteins that mediate the defense
      process. We pursued an integrated approach to identifying putative cas genes from
      genomes and metagenomes, combining similarity searches with genomic neighborhood
      analysis. Application of our approach to bacterial genomes and human microbiome
      datasets allowed us to significantly expand the collection of cas genes: the
      sequence space of the Cas9 family, the key player in the recently engineered RNA
      guided platforms for genome editing in eukaryotes, is expanded by at least two
      fold with metagenomic datasets. We found genes in cas loci encoding other
      functions, for example, toxins and antitoxins, confirming the recently discovered
      potential of coupling between adaptive immunity and the dormancy/suicide systems.
      We further identified 24 novel Cas families; one novel family contains 20
      proteins, all identified from the human microbiome datasets, illustrating the
      importance of metagenomics projects in expanding the diversity of cas genes. 

PMID- 24319143
TI  - MMDB and VAST+: tracking structural similarities between macromolecular
      complexes.
AB  - The computational detection of similarities between protein 3D structures has
      become an indispensable tool for the detection of homologous relationships, the
      classification of protein families and functional inference. Consequently,
      numerous algorithms have been developed that facilitate structure comparison,
      including rapid searches against a steadily growing collection of protein
      structures. To this end, NCBI's Molecular Modeling Database (MMDB), which is
      based on the Protein Data Bank (PDB), maintains a comprehensive and up-to-date
      archive of protein structure similarities computed with the Vector Alignment
      Search Tool (VAST). These similarities have been recorded on the level of single
      proteins and protein domains, comprising in excess of 1.5 billion pairwise
      alignments. Here we present VAST+, an extension to the existing VAST service,
      which summarizes and presents structural similarity on the level of biological
      assemblies or macromolecular complexes. VAST+ simplifies structure neighboring
      results and shows, for macromolecular complexes tracked in MMDB, lists of similar
      complexes ranked by the extent of similarity. VAST+ replaces the previous VAST
      service as the default presentation of structure neighboring data in NCBI's
      Entrez query and retrieval system. MMDB and VAST+ can be accessed via
      http://www.ncbi.nlm.nih.gov/Structure. 

PMID- 24319144
TI  - Hyperactive mariner transposons are created by mutations that disrupt allosterism
      and increase the rate of transposon end synapsis.
AB  - New applications for transposons in vertebrate genetics have spurred efforts to
      develop hyperactive variants. Typically, a genetic screen is used to identify
      several hyperactive point mutations, which are then incorporated in a single
      transposase gene. However, the mechanisms responsible for the increased activity
      are unknown. Here we show that several point mutations in the mariner transposase
      increase their activities by disrupting the allostery that normally serves to
      downregulate transposition by slowing synapsis of the transposon ends. We focused
      on the conserved WVPHEL amino acid motif, which forms part of the mariner
      transposase dimer interface. We generated almost all possible single
      substitutions of the W, V, E and L residues and found that the majority are
      hyperactive. Biochemical analysis of the mutations revealed that they disrupt
      signals that pass between opposite sides of the developing transpososome in
      response to transposon end binding. In addition to their role in allostery, the
      signals control the initiation of catalysis, thereby preventing non-productive
      double-strand breaks. Finally, we note that such breaks may explain the puzzling
      'self-inflicted wounds' at the ends of the Mos1 transposon in Drosophila. 

PMID- 24319146
TI  - The Catalytic Site Atlas 2.0: cataloging catalytic sites and residues identified
      in enzymes.
AB  - Understanding which are the catalytic residues in an enzyme and what function
      they perform is crucial to many biology studies, particularly those leading to
      new therapeutics and enzyme design. The original version of the Catalytic Site
      Atlas (CSA) (http://www.ebi.ac.uk/thornton-srv/databases/CSA) published in 2004,
      which catalogs the residues involved in enzyme catalysis in experimentally
      determined protein structures, had only 177 curated entries and employed a
      simplistic approach to expanding these annotations to homologous enzyme
      structures. Here we present a new version of the CSA (CSA 2.0), which greatly
      expands the number of both curated (968) and automatically annotated catalytic
      sites in enzyme structures, utilizing a new method for annotation transfer. The
      curated entries are used, along with the variation in residue type from the
      sequence comparison, to generate 3D templates of the catalytic sites, which in
      turn can be used to find catalytic sites in new structures. To ease the transfer
      of CSA annotations to other resources a new ontology has been developed: the
      Enzyme Mechanism Ontology, which has permitted the transfer of annotations to
      Mechanism, Annotation and Classification in Enzymes (MACiE) and UniProt Knowledge
      Base (UniProtKB) resources. The CSA database schema has been re-designed and both
      the CSA data and search capabilities are presented in a new modern web interface.

PMID- 24319145
TI  - Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis
      dependent strand annealing.
AB  - Most mitotic homologous recombination (HR) events proceed via a synthesis
      dependent strand annealing mechanism to avoid crossing over, which may give rise
      to chromosomal rearrangements and loss of heterozygosity. The molecular
      mechanisms controlling HR sub-pathway choice are poorly understood. Here, we show
      that human RECQ5, a DNA helicase that can disrupt RAD51 nucleoprotein filaments,
      promotes formation of non-crossover products during DNA double-strand break
      induced HR and counteracts the inhibitory effect of RAD51 on RAD52-mediated DNA
      annealing in vitro and in vivo. Moreover, we demonstrate that RECQ5 deficiency is
      associated with an increased occupancy of RAD51 at a double-strand break site,
      and it also causes an elevation of sister chromatid exchanges on inactivation of
      the Holliday junction dissolution pathway or on induction of a high load of DNA
      damage in the cell. Collectively, our findings suggest that RECQ5 acts during the
      post-synaptic phase of synthesis-dependent strand annealing to prevent formation
      of aberrant RAD51 filaments on the extended invading strand, thus limiting its
      channeling into potentially hazardous crossover pathway of HR. 

PMID- 24319147
TI  - A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA
      helices and accelerates strand annealing.
AB  - For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner
      capsids function as the machinery for viral RNA (vRNA) replication. Unlike other
      multishelled reoviruses, cypovirus has a single-layered capsid, thereby
      representing a simplified model for studying vRNA replication of reoviruses. VP5
      is one of the three major cypovirus capsid proteins and functions as a clamp
      protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5
      Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined
      that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA
      helices and accelerates strand annealing independent of ATP. Our further
      characterization of VP5 revealed that its helix-destabilizing activity is RNA
      specific, lacks directionality and could be inhibited by divalent ions, such as
      Mg(2+), Mn(2+), Ca(2+) or Zn(2+), to varying degrees. Furthermore, we found that
      HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase
      (i.e. reverse transcriptase) through a panhandle-structured RNA template, which
      mimics the 5'-3' cyclization of cypoviral positive-stranded RNA. Given that the
      replication of negative-stranded vRNA on the positive-stranded vRNA template
      necessitates the dissociation of the 5'-3' panhandle, the RNA chaperone activity
      of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis. 

PMID- 24319149
TI  - Associations between race, lifecourse socioeconomic position and prevalence of
      diabetes among US women and men: results from a population-based panel study.
AB  - BACKGROUND: Few studies have examined the degree to which racial disparities in
      the development of diabetes are accounted by differences in lifecourse
      socioeconomic position (SEP). We assessed the association between race,
      lifecourse SEP measures and prevalence of diabetes in a representative US sample
      of black and white adults. METHODS: A generalised estimating equations approach
      was used with a sample of 3497 adults from the Americans' Changing Lives study.
      Sex-specific models were calculated to compute prevalence ratios (PR) for
      associations of race and SEP with self-reported diagnoses of diabetes. RESULTS:
      For men, childhood and adult SEP were unrelated to diabetes, and adjustment for
      lifecourse SEP had little effect on the excess diabetes in blacks (PR=1.56, 95%
      CI 1.11 to 2.21). Adjustment for measures of lifecourse SEP reduced the PR for
      the association between race and diabetes in women from 1.96 (95% CI 1.52 to
      2.54) to 1.40 (95% CI 1.04 to 1.87) with the respondent's education responsible
      for most of the reduction in the association. However, diabetes was also
      inversely associated with father's education, and low SEP throughout the
      lifecourse was associated with a nearly threefold increase in diabetes (PR=2.89,
      95% CI 2.10 to 3.99). CONCLUSIONS: Racial disparities in diabetes existed among
      both men and women, but lifecourse SEP was related to diabetes only among women.
      The pathway and cumulative hypotheses for lifecourse SEP effects on diabetes may
      be especially salient for women.

PMID- 24319150
TI  - On the role of social support on macroeconomic determinants on elderly people
      health: a hypothesis about a counterexample in Spain.

PMID- 24319148
TI  - Identification of genes involved in low aminoglycoside-induced SOS response in
      Vibrio cholerae: a role for transcription stalling and Mfd helicase.
AB  - Sub-inhibitory concentrations (sub-MIC) of antibiotics play a very important role
      in selection and development of resistances. Unlike Escherichia coli, Vibrio
      cholerae induces its SOS response in presence of sub-MIC aminoglycosides. A role
      for oxidized guanine residues was observed, but the mechanisms of this induction
      remained unclear. To select for V. cholerae mutants that do not induce low
      aminoglycoside-mediated SOS induction, we developed a genetic screen that renders
      induction of SOS lethal. We identified genes involved in this pathway using two
      strategies, inactivation by transposition and gene overexpression. Interestingly,
      we obtained mutants inactivated for the expression of proteins known to
      destabilize the RNA polymerase complex. Reconstruction of the corresponding
      mutants confirmed their specific involvement in induction of SOS by low
      aminoglycoside concentrations. We propose that DNA lesions formed on
      aminoglycoside treatment are repaired through the formation of single-stranded
      DNA intermediates, inducing SOS. Inactivation of functions that dislodge RNA
      polymerase leads to prolonged stalling on these lesions, which hampers SOS
      induction and repair and reduces viability under antibiotic stress. The
      importance of these mechanisms is illustrated by a reduction of aminoglycoside
      sub-MIC. Our results point to a central role for transcription blocking at DNA
      lesions in SOS induction, so far underestimated. 

PMID- 24319151
TI  - In memoriam: Elwood Jensen (1920-2012).

PMID- 24319152
TI  - In memoriam: William H. Daughaday, MD (1918-2013).

PMID- 24319154
TI  - Iron and hepcidin: a story of recycling and balance.
AB  - To avoid iron deficiency and overload, iron availability is tightly regulated at
      both the cellular and systemic levels. The liver peptide hepcidin controls iron
      flux to plasma from enterocytes and macrophages through degradation of the
      cellular iron exporter ferroportin. The hepcidin-ferroportin axis is essential to
      maintaining iron homeostasis. Genetic inactivation of proteins of the hepcidin
      activating pathway causes iron overload of varying severity in human and mice.
      Hepcidin insufficiency and increased iron absorption are also characteristic of
      anemia due to ineffective erythropoiesis in which, despite high total body iron,
      hepcidin is suppressed by the high erythropoietic activity, worsening both iron
      overload and anemia in a vicious cycle. Hepcidin excess resulting from genetic
      inactivation of a hepcidin inhibitor, the transmembrane protease serine 6
      (TMPRSS6) leads to a form of iron deficiency refractory to oral iron. Increased
      hepcidin explains the iron sequestration and iron-restricted erythropoiesis of
      anemia associated with chronic inflammatory diseases. In mice, deletion of
      TMPRSS6 in vivo has profound effects on the iron phenotype of hemochromatosis and
      beta-thalassemia. Hepcidin manipulation to restrict iron is a successful strategy
      to improve erythropoiesis in thalassemia, as shown clearly in preclinical studies
      targeting TMPRSS6; attempts to control anemia of chronic diseases by antagonizing
      the hepcidin effect are ongoing. Finally, the metabolic pathways identified from
      iron disorders are now being explored in other human pathologic conditions,
      including cancer. 

PMID- 24319155
TI  - The ASH Choosing Wisely(r)campaign: five hematologic tests and treatments to
      question.
AB  - Choosing Wisely(r) is a medical stewardship and quality improvement initiative
      led by the American Board of Internal Medicine Foundation in collaboration with
      leading medical societies in the United States. The ASH is an active participant
      in the Choosing Wisely(r) project. Using an iterative process and an evidence
      based method, ASH has identified 5 tests and treatments that in some
      circumstances are not well supported by evidence and which in certain cases
      involve a risk of adverse events and financial costs with low likelihood of
      benefit. The ASH Choosing Wisely(r) recommendations focus on avoiding liberal RBC
      transfusion, avoiding thrombophilia testing in adults in the setting of transient
      major thrombosis risk factors, avoiding inferior vena cava filter usage except in
      specified circumstances, avoiding the use of plasma or prothrombin complex
      concentrate in the nonemergent reversal of vitamin K antagonists, and limiting
      routine computed tomography surveillance after curative-intent treatment of non
      Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated
      benefits of the identified tests and treatments before performing them. 

PMID- 24319156
TI  - Phase 4 research: what happens when the rubber meets the road?
AB  - Approval of a novel drug is oftentimes seen as the end of the development
      pathway. However, the appearance of rare but serious side effects in patients
      taking approved drugs has led to increased attention to phase 4, or
      postmarketing, research. Traditionally, postmarketing research relied on reports
      from clinicians to monitor for unexpected toxicity. However, such reporting will
      produce a biased assessment of risk due to underreporting of toxic effects in
      older medications. The availability of large, representative databases and more
      flexible analysis tools has led to comprehensive and near "real-time"
      surveillance programs. These programs have been used by the US Food and Drug
      Administration to explore toxicities of approved medications. The need for
      effective tools with which to monitor clinically relevant outcome events has been
      further increased by the development of accelerated pathways to drug approval. In
      areas without effective treatments, such pathways lead to licensure without
      rigorous clinical efficacy data. Continued approval is frequently made contingent
      on the availability of postmarketing surveillance data demonstrating improvements
      in clinical end points and these data can also be used to monitor for unexpected
      toxicity. 

PMID- 24319157
TI  - Drug discovery in rare indications: opportunities and challenges.
AB  - Over the past decade, the number of new therapies developed for the treatment of
      rare diseases continues to increase. The most rapid growth has been in the
      development of new drugs for oncology indications. One focus in drug discovery
      for oncology indications is the development of targeted therapies for select
      patient subgroups characterized by genetic alterations. The identification of
      these patient subgroups has increased in the past decade and has resulted in a
      corresponding increase in the development of new drugs for genetically defined
      patient subgroups. As an example of the development of new therapeutics for rare
      indications, I describe here the drug discovery efforts leading to the
      development of DOT1L inhibitors for the treatment of MLL-rearranged leukemia. 

PMID- 24319158
TI  - Accelerating safe drug development: an ideal approach to approval.
AB  - Although enormous progress in therapeutic research has improved the lives of
      patients with hematologic malignancies, these earlier achievements resulted from
      strategic combinations of agents with unique mechanisms of action and
      nonoverlapping toxicities. Continued investment in the modern era of drug
      discovery and development will focus on targeted therapies. Targeting of specific
      molecular pathways is expected to achieve effective tumor cell reduction with
      less overall toxicity. The translational processes involved in moving novel
      therapeutic strategies from the laboratory toward the clinic require close
      monitoring. The efforts in both cancer drug discovery and development will
      require extensive collaboration among basic scientists, clinical investigators,
      and regulatory scientists. The transition from older methods of therapeutic
      research will require laboratory support to define eligible patients based upon
      their pretreatment profile. The principles of preclinical drug development based
      upon decades of experience in predicting toxicity and designing therapeutic
      strategies are still needed to insure that safety is a high priority. The
      opportunities for developing novel targeted combination therapies in uniquely
      profiled patients will hopefully enable successful breakthroughs. Several
      concrete examples of exciting new agents are discussed here. Defining the
      predicted mechanism of resistance to these new targeted agents will enable
      investigators to subsequently design strategies to circumvent resistance with
      effective combinations. Drug discovery and development are complex and expensive,
      so efficiency and cooperation in task completion must be tracked. 

PMID- 24319159
TI  - Molecular approaches for improved clotting factors for hemophilia.
AB  - Hemophilia is caused by a functional deficiency of one of the coagulation
      proteins. Therapy for no other group of genetic diseases has seen the progress
      that has been made for hemophilia over the past 40 years, from a life expectancy
      in 1970 of ~20 years for a boy born with severe hemophilia to essentially a
      normal life expectancy in 2013 with current prophylaxis therapy. However, these
      therapies are expensive and require IV infusions 3 to 4 times each week. These
      are exciting times for hemophilia because several new technologies that promise
      extended half-lives for factor products, with potential for improvements in
      quality of life for persons with hemophilia, are in late-phase clinical
      development.

PMID- 24319160
TI  - Long-lasting recombinant factor VIII proteins for hemophilia A.
AB  - In the past 50 years, the lifespan of an individual affected with severe
      hemophilia A has increased from a mere 20 years to near that of the general
      unaffected population. These advances are the result of and parallel advances in
      the development and manufacture of replacement therapies. We are now poised to
      witness further technologic leaps with the development of longer-lasting
      replacement therapies, some of which are likely to be approved for market
      shortly. Prophylactic therapy is currently the standard of care for young
      children with severe hemophilia A, yet requires frequent infusion to achieve
      optimal results. Longer-lasting products will transform our ability to deliver
      prophylaxis, especially in very young children. Longer-lasting replacement
      therapies will require changes to our current treatment plans including those for
      acute bleeding, prophylaxis, surgical interventions, and even perhaps
      immunotolerance induction. Ongoing observation will be required to determine the
      full clinical impact of this new class of products. 

PMID- 24319161
TI  - The old and new: PCCs, VIIa, and long-lasting clotting factors for hemophilia and
      other bleeding disorders.
AB  - What is the correct use of established clotting factors, prothrombin complex
      concentrates (PCCs), and activated factor VII in bleeding complications of
      trauma, surgery, and old and new oral anticoagulants? How will new clotting
      factors, specifically the long-acting factors, change the hemostatic management
      of coagulation deficiency disorders? From bench to bedside, comparative
      coagulation studies and clinical trials of modified clotting factors are
      providing insights to help guide hemostatic management of congenital and acquired
      bleeding disorders. Comparative thrombin-generation studies and preclinical and
      clinical trials suggest that PCCs and fresh-frozen plasma are effective in
      reversing the anticoagulant effects of warfarin, yet there are few data to guide
      reversal of the new oral anticoagulants dabigatran and rivaroxaban. Although
      coagulation studies support the use of PCCs to reverse new oral anticoagulants,
      correlation with clinical response is variable and clinical trials in bleeding
      patients are needed. For congenital bleeding disorders, exciting new technologies
      are emerging from the bench. Data from clinical trials of molecularly modified
      coagulation factors with extended half-lives suggest the possibility of fewer
      infusions, reduced bleeds, and better quality of life in persons with hemophilia.
      Preclinical studies of other novel prohemostatic approaches for hemophilia and
      other congenital coagulation disorders include RNA interference silencing of
      antithrombin, monoclonal anti-tissue factor pathway inhibitor (anti-antibody,
      anti-tissue factor pathway inhibitor) aptamer, bispecific anti-IXa/X antibody,
      and fucoidans. Understanding the comparative coagulation studies of established
      prohemostatic agents, the pharmacokinetics of new long-acting clotting factors,
      and their correlation with bleeding outcomes will provide opportunities to
      optimize the hemostatic management of both congenital and acquired hemostatic
      disorders. 

PMID- 24319162
TI  - What is the role of prophylaxis in the improvement of health-related quality of
      life of patients with hemophilia?
AB  - A 32-year-old male with severe hemophilia presents for his annual evaluation. He
      has a history of multiple joint bleeds that he has always treated on-demand, that
      is, after they occur. You have recommended prophylaxis, that is, preventively,
      before they occur, to decrease his episodes of bleeding; however, he had been
      reluctant to comply in the past. He is having difficulty keeping up at work
      because of interruptions, pain, and lost time at work. He is willing to consider
      a trial of prophylaxis. You discuss the impact of hemophilia on his health
      related quality of life (HRQOL) and consider measuring his HRQOL over time using
      a generic measure of HRQOL to determine whether prophylaxis will reduce
      interruptions, pain, and lost time from work and improve his HRQOL. 

PMID- 24319163
TI  - Allogeneic transplantation for AML and MDS: GVL versus GVHD and disease
      recurrence.
AB  - Allogeneic transplantation constitutes curative treatment for acute myeloid
      leukemia and myelodysplastic syndrome. Its therapeutic effects are to a large
      extent mediated by GVL effects, but partially offset by treatment-related
      mortality and loss of quality of life caused by acute and chronic GVHD. Although
      severe acute and chronic GVHD are associated with a reduction in relapse risk,
      they are not associated with improved survival. Recent efforts to modulate the
      GVL-GVH balance include novel methods of in vitro or in vivo T-cell depletion
      that are associated with a minimal impact on rates of disease recurrence and a
      dramatically decreased risk for GVHD. Donor selection algorithms may also have a
      significant impact on transplantation outcomes. Low-expression HLA alleles,
      particularly HLA-DP, should be incorporated in selection of adult unrelated
      donors. Evolving data suggest that KIR typing may also be important. High
      resolution HLA typing and the importance of fetal-maternal interactions in
      umbilical cord blood transplantation are also briefly discussed. A combination of
      donor selection strategies and GVHD prophylaxis methods will favorably affect
      long-term outcomes and create an environment suitable for effective
      posttransplantation interventions. 

PMID- 24319164
TI  - Pharmacological methods to reduce disease recurrence.
AB  - Allogeneic stem cell transplantation is an increasingly important treatment
      option in patients with high-risk acute myeloid leukemia (AML) and
      myelodysplastic syndrome (MDS). Although there has been substantial progress in
      reducing transplantation-related mortality (TRM), little progress has been made
      in reducing the risk of disease relapse, which continues to represent the major
      cause of treatment failure in patients allografted for AML and MDS. Experience
      with myeloablative conditioning regimens has demonstrated that, although
      intensification of the preparative regimen reduces relapse risk, any survival
      benefit is blunted by a concomitant increase in TRM. A similar inverse
      correlation between relapse risk and TRM is observed in patients allografted
      using a reduced-intensity conditioning regimen. However, the markedly lower
      toxicity of such regimens has permitted the design of novel conditioning
      strategies aimed at maximizing antitumor activity without excessive transplant
      toxicity. Coupled with recent advances in drug delivery and design, this has
      allowed the development of a spectrum of new conditioning regimens in patients
      with high-risk AML and MDS. At the same time, the optimization of a graft-versus
      leukemia (GVL) effect by minimizing posttransplantation immunosuppression, with
      or without the infusion of donor lymphocytes, is essential if the risk of disease
      relapse is to be reduced. Recently, the delivery of adjunctive
      posttransplantation therapies has emerged as a promising method of augmenting
      antileukemic activity, either through a direct antitumor activity or consequent
      upon pharmacological manipulation of the alloreactive response. Taken together
      these advances present a realistic possibility of delivering improved outcome in
      patients allografted for high-risk AML or MDS. 

PMID- 24319165
TI  - Older patients/older donors: choosing wisely.
AB  - Two lingering problems regarding transplantation in older adults have been how to
      select patients appropriately and whether to use older sibling donors. Allogeneic
      hematopoietic cell transplantation (HCT) of older patients may result in long
      term survival due to GVL, but the data remain observational and mostly restricted
      to those 50 to 69 years of age. Patients with excellent performance status and
      low comorbidity have the best long-term survival after HCT. Novel measures of
      health status such as self-report or performance-based functional measures allow
      "staging the age" and may inform candidacy for less robust patients. Older
      matched sibling donors should be preferred over matched unrelated donors (MUDs)
      because outcomes are equivalent to superior for matched sibling donors compared
      with MUD. However, MUDs also achieve acceptable outcomes and long-term disease
      control. An alternative donor can be considered based on institutional protocols
      and expertise. Very limited information is available in patients or related
      donors 70 years of age and older. Future efforts to more completely characterize
      patient health status before transplantation will allow better application of HCT
      in older adults. 

PMID- 24319166
TI  - Current concepts in the pathophysiology and treatment of aplastic anemia.
AB  - Historically viewed in isolation as an odd, rare, and invariably fatal blood
      disease, aplastic anemia is now of substantial interest for its immune
      pathophysiology, its relationship to constitutional BM failure syndromes and
      leukemia, and the success of both stem cell transplantation and immunosuppressive
      therapies in dramatically improving survival of patients. Once relegated to a few
      presentations in the red cell and anemia sessions of the ASH, the Society now
      sponsors multiple simultaneous sessions and plenary and scientific committee
      presentations on these topics. This update emphasizes developments in our
      understanding of immune mechanisms and hematopoietic stem cell biology and new
      clinical approaches to stem cell stimulation as a therapy, alone and in
      combination with conventional suppression of the aberrant immune system. 

PMID- 24319167
TI  - Allogeneic BM transplantation for the treatment of aplastic anemia: current
      results and expanding donor possibilities.
AB  - Allogeneic BM transplantation from an HLA-identical sibling donor leads to long
      term survival in the majority of patients (>80%). Therefore, survival is no
      longer the sole concern and attention has to be paid to decreasing the incidence
      and severity of long-term complications. For patients without a sibling donor,
      transplantation from a well-matched unrelated donor can be considered after
      failure of a previous course of immunosuppressive therapy. After transplantation
      from an HLA-identical sibling donor or from an unrelated one, the use of
      peripheral blood stem cells must be strongly discouraged because they have been
      systematically associated with an increased incidence of chronic GVHD compared
      with the use of BM as a stem cell source, leading to an unacceptably higher risk
      of treatment-related mortality in this setting. For as yet unknown reasons, the
      age limit after which transplantation results are less satisfactory remains 40
      years of age.

PMID- 24319168
TI  - Management of the refractory aplastic anemia patient: what are the options?
AB  - Refractory aplastic anemia (AA) is defined as a lack of response to first-line
      immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and
      is manifested as persistence of severe cytopenias at 6 months after IST. Although
      supportive care is critical for AA patients, it is of paramount importance for
      refractory disease in view of the longer duration of pancytopenia and
      susceptibility to life-threatening infections due to IST. Improvements in
      supportive care have largely contributed to better outcome over the past 2
      decades, with 5-year overall survival reaching 57% during 2002 to 2008 for
      patients with AA unresponsive to initial IST. Exclusion of hypocellular
      myelodysplastic syndrome and constitutional BM failure masquerading as apparent
      idiopathic AA should be done in conjunction with centers of excellence.
      Hematopoietic stem cell transplantation is indicated if refractory AA patients
      are fit and have a suitably matched donor, either a sibling (>40-50 years) or
      unrelated donor. Patients lacking a fully matched donor should be considered for
      a second course of antithymocyte globulin plus cyclosporin, although response in
      the refractory setting is only ~30% to 35%. Response may also occur with
      alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The
      emerging data for alternate donor (cord or haploidentical) transplantation in AA
      has provided additional therapeutic choices to consider in refractory disease.

PMID- 24319169
TI  - EBV and posttransplantation lymphoproliferative disease: what to do?
AB  - This review summarizes the available evidence and outlines our approach to the
      prophylaxis and management of posttransplantation lymphoproliferative disorder
      (PTLD) in adult solid organ transplantation recipients. We attempt to reduce
      immunosuppression as tolerated in every patient with suspected PTLD in close
      cooperation with their transplantation physician. There is no evidence to guide
      the decision when to initiate further treatment; we usually wait no longer than 4
      weeks and always initiate further therapy unless there is a complete or at least
      good partial remission. If clinical and histological findings indicate rapidly
      progressive disease, we initiate additional therapy significantly earlier. CD20
      positive PTLD accounts for approximately 75% of PTLD cases. Outside of clinical
      trials, we currently regard sequential therapy with rituximab and CHOP
      (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone)
      chemotherapy as standard evidence-based treatment for CD20-positive PTLD
      unresponsive to immunosuppression. We also discuss our approach to the rare
      instance of adults with PTLD associated with primary EBV infection, localized
      (stage I) disease, rare PTLD subtypes, and refractory/relapsed disease based on
      the available retrospective data and our own experience. In addition to
      immunotherapy and chemotherapy, this includes local therapy approaches such as
      surgery and radiotherapy in stage I disease, plasmacytoma-like PTLD, and primary
      CNS PTLD. We also provide our view on the current indications for the use of
      allogeneic cytotoxic T cells, even though this treatment modality is so far
      unavailable in our clinical practice. 

PMID- 24319170
TI  - Human herpesvirus-8: Kaposi sarcoma, multicentric Castleman disease, and primary
      effusion lymphoma.
AB  - Human herpesvirus 8 (HHV8) is a gamma herpesvirus associated with Kaposi sarcoma,
      multicentric Castleman disease, and primary effusion lymphoma,
      lymphoproliferative diseases that are most commonly observed in immunocompromised
      individuals. The viral genome expresses genes responsible for inhibition of
      apoptosis, cell cycle entry, and angiogenesis. Viral homologs of human regulatory
      genes are expressed, providing stimuli for angiogenesis, B-cell proliferation,
      and immune evasion. Variations in expression of these factors give rise to the 3
      known HHV8-associated malignancies. Identification of these pathogenetic
      mechanisms has led to exploration of targeted treatment approaches for all 3 of
      these disorders with success in Kaposi sarcoma and multicentric Castleman
      disease; primary effusion lymphoma remains a clinical challenge. 

PMID- 24319171
TI  - Helicobacter pylori and mucosa-associated lymphoid tissue: what's new.
AB  - Low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach,
      gastric MALT lymphoma, is associated with Helicobacter pylori infection. The
      eradication of H pylori using antibiotics is successful in 60% to 80% of affected
      patients. In contrast to the previous paradigm, we and other investigators have
      shown that a certain proportion of patients with H pylori-positive early-stage
      diffuse large B-cell lymphoma (DLBCL) of the stomach with histological evidence
      of MALT lymphoma, including high-grade transformed gastric MALT lymphoma and
      gastric DLBCL(MALT), achieved long-term complete pathological remission (pCR)
      after first-line H pylori eradication therapy, indicating that the loss of H
      pylori dependence and high-grade transformation are separate events in the
      progression of gastric lymphoma. In addition, patients with H pylori-positive
      gastric DLBCL without histological evidence of MALT (gastric pure DLBCL) may also
      respond to H pylori eradication therapy. A long-term follow-up study showed that
      patients who achieved pCR remained lymphoma free. Gastric MALT lymphoma is
      indirectly influenced by H pylori infection through T-cell stimulation, and
      recent studies have shown that H pylori-triggering chemokines and their
      receptors, H pylori-associated epigenetic changes, H pylori-regulated miRNA
      expression, and tumor infiltration by CD4+CD25+ regulatory T cells contribute to
      lymphomagenesis of gastric MALT lymphoma. Recent studies have also demonstrated
      that the translocation of CagA into B lymphocytes inhibits apoptosis through p53
      accumulation, BAD phosphorylation, and the up-regulation of Bcl-2 and Bcl-XL
      expression. In gastric MALT lymphoma, CagA may stimulate lymphomagenesis
      directly, through the regulation of signal transduction, and intracellular CagA
      is associated with H pylori dependence. These findings represent a substantial
      paradigm shift compared with the classical theory of H pylori-reactive T cells
      contributing indirectly to the development of MALT lymphoma. In conclusion, a
      wide range of H pylori-related gastric lymphomas have been identified. The use of
      antibiotics as the sole first-line therapy for early-stage gastric pure DLBCL
      requires validation in a prospective study. The clinical and biological
      significance of the CagA oncoprotein in the lymphomagenesis of gastric MALT
      lymphoma warrants further study.

PMID- 24319172
TI  - Targeting signaling pathways in acute lymphoblastic leukemia: new insights.
AB  - The genetics of acute lymphoblastic leukemia are becoming well understood and the
      incidence of individual chromosomal abnormalities varies considerably with age.
      Cytogenetics provide reliable risk stratification for treatment: high
      hyperdiploidy and ETV6-RUNX1 are good risk, whereas BCR-ABL1, MLL rearrangements,
      and hypodiploidy are poor risk. Nevertheless, some patients within the good- and
      intermediate-risk groups will unpredictably relapse. With advancing technologies
      in array-based approaches (single nucleotide polymorphism arrays) and next
      generation sequencing to study the genome, increasing numbers of new genetic
      changes are being discovered. These include deletions of B-cell differentiation
      and cell cycle control genes, as well as mutations of genes in key signaling
      pathways. Their associations and interactions with established cytogenetic
      subgroups and with each other are becoming elucidated. Whether they have a link
      to outcome is the most important factor for refinement of risk factors in
      relation to clinical trials. For several newly identified abnormalities,
      including intrachromosomal amplification of chromosome 21 (iAMP21), that are
      associated with a poor prognosis with standard therapy, appropriately modified
      treatment has significantly improved outcome. After the successful use of
      tyrosine kinase inhibitors in the treatment of BCR-ABL1-positive acute
      lymphoblastic leukemia, patients with alternative ABL1 translocations and
      rearrangements involving PDGFRB may benefit from treatment with tyrosine kinase
      inhibitors. Other aberrations, for example, CRLF2 overexpression and JAK2
      mutations, are also providing potential novel therapeutic targets with the
      prospect of reduced toxicity. 

PMID- 24319173
TI  - Pharmacogenomics of acute lymphoid leukemia: new insights into treatment toxicity
      and efficacy.
AB  - Childhood acute lymphoblastic leukemia (ALL) provides an outstanding model for
      pharmacogenomic research: it is a drug-responsive disseminated cancer that is
      cured with medications alone in ~ 85% of patients, but relapse remains
      unacceptably high for some subgroups. Inherited genomic variation contributes to
      the risk of relapse and to the risk of short- and long-term serious adverse
      effects of therapy. Our goal is to identify the inherited genomic variants that
      contribute to interindividual differences in response in patients with ALL. We
      discuss results of whole-genome interrogations of germline DNA in ALL. 

PMID- 24319174
TI  - New immune strategies for the treatment of acute lymphoblastic leukemia:
      antibodies and chimeric antigen receptors.
AB  - The prognosis of adult acute lymphoblastic leukemia (ALL) remains poor and novel
      treatment strategies are needed. Antibody-based therapies represent such an
      approach. ALL cells express various surface antigens that are targets for
      monoclonal antibodies. This review focuses on 4 major classes of antibody
      therapy: (1) naked antibodies, (2) T-cell-engaging bispecific single-chain
      antibodies, (3) immunoconjugates/immunotoxins, and (4) chimeric antigen
      receptors. Preclinical and clinical data are reviewed. This area of research
      represents an exciting new approach to help improve the outcome of this disease.
      Several clinical trials are currently incorporating this therapy in the treatment
      of newly diagnosed and relapsed adult ALL patients. 

PMID- 24319175
TI  - Signaling the end of chronic lymphocytic leukemia: new frontline treatment
      strategies.
AB  - The management of chronic lymphocytic leukemia (CLL) is undergoing profound
      changes. Several new drugs have been approved for CLL treatment (fludarabine,
      bendamustine, and the monoclonal antibodies alemtuzumab, rituximab, and
      ofatumumab) and many more drugs are in advanced clinical development to be
      approved for this disease. In addition, the extreme heterogeneity of the clinical
      course and our improved ability to foresee the prognosis of this leukemia by the
      use of clinical, biological, and genetic parameters now allow us to characterize
      patients with a very mild onset and course, an intermediate prognosis, or a very
      aggressive course with high-risk leukemia. Therefore, it becomes increasingly
      challenging to select the right treatment strategy for each condition. This
      article summarizes the currently available diagnostic and therapeutic tools and
      gives an integrated recommendation of how to manage CLL in 2013. Moreover, I
      propose a strategy how we might integrate the novel agents for CLL therapy into
      sequential treatment approaches in the near future. 

PMID- 24319176
TI  - Immunotherapeutic strategies including transplantation: eradication of disease.
AB  - Although there have been recent advances with targeted therapies in chronic
      lymphocytic leukemia (CLL), chemoimmunotherapy remains the treatment of choice;
      however, this approach is not curative. A key feature of CLL is that it induces a
      state of immunosuppression, causing increased susceptibility to infections and
      failure of an antitumor immune response, often worsened by the immunosuppressive
      effect of treatment. Because of its improved specificity, immunotherapy
      potentially offers a way out of this dilemma. Allogeneic stem cell
      transplantation remains the only curative option, but is hampered by the toxicity
      of GVHD. After many years of promise but little reward, many other
      immunotherapeutic approaches are now in transition to the clinical setting.
      Clinical trials including CLL vaccines, CXCR4 antagonists, and adoptive cellular
      immunotherapies such as chimeric antigen receptor-modified T cells, CD40 ligand
      gene therapy, and the immunomodulatory drug lenalidomide are ongoing. Results to
      date suggest that immunotherapeutic approaches for the treatment of CLL might
      finally be fulfilling their promise. 

PMID- 24319177
TI  - Treatment of older patients with chronic lymphocytic leukemia: key questions and
      current answers.
AB  - Despite the advanced age at onset, chronic lymphocytic leukemia (CLL) shortens
      the life expectancy of the majority of newly diagnosed patients. The management
      of elderly patients with CLL is more complex than that of younger patients due to
      the greater frequency of comorbidities and functional impairment as well as
      reduced organ function. Many of the recent advances in the care of CLL patients
      (prognostication, more intense combination therapy regimens) are of unclear
      relevance for elderly patients. This review addresses 5 key questions in the
      management of elderly patients with CLL: (1) why is classifying the "fitness" of
      CLL patients necessary; (2) what criteria should be used to classify patient
      fitness; (3) when should elderly patients be treated; (4) how should therapy be
      selected for elderly patients; and (5) which therapy is best (for this patient)? 

PMID- 24319178
TI  - Which TKI? An embarrassment of riches for chronic myeloid leukemia patients.
AB  - With the approval in many countries of nilotinib and dasatinib for frontline
      therapy in chronic myeloid leukemia, clinicians now have to make a difficult
      choice. Because none of the 3 available tyrosine kinase inhibitors (TKIs) have
      shown a clear survival advantage, they all represent reasonable choices. However,
      in individual patients, the case may be stronger for a particular TKI. In the
      younger patient, in whom the prospect of eventually achieving treatment-free
      remission is likely to be of great importance, dasatinib or nilotinib may be
      preferred, although their advantage over imatinib in this setting remains to be
      proven. In patients with a higher risk of transformation (which is currently
      based on prognostic scoring), the more potent TKIs may be preferred because they
      appear to be more effective at reducing the risk of transformation to BC.
      However, imatinib still represents an excellent choice for many chronic myeloid
      leukemia patients. All of these considerations need to be made in the context of
      the patient's comorbidities, which may lead to one or more TKIs being ruled out
      of contention. Whatever first choice of TKI is made, treatment failure or
      intolerance must be recognized early because a prompt switch to another TKI
      likely provides the best chance of achieving optimal response. 

PMID- 24319179
TI  - Update on current monitoring recommendations in chronic myeloid leukemia:
      practical points for clinical practice.
AB  - Excellent therapeutic options exist for the treatment of chronic-phase chronic
      myeloid leukemia (CML) patients. Therefore, managing CML patients has become a
      more common practice for many physicians. Most chronic-phase CML patients achieve
      durable cytogenetic and molecular responses on first-line tyrosine kinase
      inhibitor therapy. However, careful monitoring and assessment of adherence are
      essential for successful outcomes and to identify patients at risk for failing
      therapy. The European LeukemiaNet and National Comprehensive Cancer Network
      provide guidance and strategies for monitoring and managing patients treated with
      TKIs. These recommendations continue to evolve as approved treatment options
      expand to include second- and third-generation tyrosine kinase inhibitors. How
      measurements of response are defined and data supporting recent recommended
      changes to monitoring are reviewed here. These changes include increasing
      recognition of the importance of early response. The relevance of achieving deep
      molecular responses will also be addressed. 

PMID- 24319180
TI  - Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when
      is this a safe option to consider?
AB  - Mrs G is a 54-year-old woman with a diagnosis of chronic-phase chronic myeloid
      leukemia dating back 8 years. She had a low-risk Sokal score at diagnosis and was
      started on imatinib mesylate at 400 mg orally daily within one month of her
      diagnosis. Her 3-month evaluation revealed a molecular response measured by
      quantitative RT-PCR of 1.2% by the International Scale. Within 6 months of
      therapy, she achieved a complete cytogenetic response, and by 18 months, her BCR
      ABL1 transcript levels were undetectable using a quantitative RT-PCR assay with a
      sensitivity of >= 4.5 logs. She has maintained this deep level of response for
      the past 6.5 years. Despite her excellent response to therapy, she continues to
      complain of fatigue, intermittent nausea, and weight gain. She is asking to
      discontinue imatinib mesylate and is not interested in second-line therapy. Is
      this a safe and reasonable option for this patient? 

PMID- 24319182
TI  - High-risk acute myelogenous leukemia: treatment today ... and tomorrow.
AB  - High-risk acute myelogenous leukemia (AML) constitutes a distinct subset of
      disease based on clinical and biological characteristics and comprises a
      significant percentage of all cases of adult AML. Biologic features such as
      distinct clonal cytogenetic and molecular abnormalities identify a subgroup of
      AML patients characterized by poor response to induction chemotherapy and poor
      long-term survival after treatment with consolidation chemotherapy. Clinical
      variables that predict for poor response include AML relapsed after less than 1
      year of remission and AML characterized by resistance to conventional agents. We
      review here our understanding of the defining biologic subtypes of AML and
      discuss how adequate initial evaluation can be used to inform the choice of
      treatment. By defining high-risk biologic and clinical variables, a strong case
      can be made for treating patients with investigational agents, with treatment
      directed at distinct cytogenetic or molecular abnormalities. Allogeneic
      transplantation is the only form of therapy available outside of the setting of a
      clinical trial that may offer a chance for long-term survival for patients with
      high-risk AML. 

PMID- 24319183
TI  - Core-binding factor acute myeloid leukemia: can we improve on HiDAC
      consolidation?
AB  - Acute myeloid leukemia (AML) with t(8;21) or inv(16) is commonly referred to as
      core-binding factor AML (CBF-AML). The incorporation of high-dose cytarabine for
      postremission therapy has substantially improved the outcome of CBF-AML patients,
      especially when administered in the setting of repetitive cycles. For many years,
      high-dose cytarabine was the standard treatment in CBF-AML resulting in favorable
      long-term outcome in approximately half of the patients. Therefore, CBF-AML
      patients are generally considered to be a favorable AML group. However, a
      substantial proportion of patients cannot be cured by the current treatment.
      Additional genetic alterations discovered in CBF-AML help in our understanding of
      the process of leukemogenesis and some of them may refine the risk assessment in
      CBF-AML and, importantly, also serve as targets for novel therapeutic approaches.
      We discuss the clinical and genetic heterogeneity of CBF-AML, with a particular
      focus on the role of KIT mutations as a prognosticator, and also discuss recent
      efforts to target the KIT kinase in the context of existing therapeutic regimens.

PMID- 24319181
TI  - Alternative approaches to eradicating the malignant clone in chronic myeloid
      leukemia: tyrosine-kinase inhibitor combinations and beyond.
AB  - In patients with chronic myeloid leukemia (CML) in chronic phase who have
      achieved complete molecular remission on imatinib therapy, clinical trials from
      France and Australia have demonstrated that the majority experience prompt
      molecular relapse of their leukemia upon discontinuation of the drug, showing
      that long-term monotherapy with tyrosine kinase inhibitors is not curative in the
      majority of patients with CML. This has focused attention on strategies to
      eradicate residual disease in CML that is presumed to arise from malignant Ph+
      stem cells, which should result in permanent cure and long-term leukemia-free
      survival. Here, we review the evidence that targeting CML stem cells will be of
      clinical benefit and discuss pharmacological and immunological approaches to
      accomplish this goal. Where possible, we link preclinical studies of CML stem
      cell biology to emerging results from clinical trials of agents that may target
      these cells.

PMID- 24319185
TI  - Utilization of mouse models to decipher natural killer cell biology and potential
      clinical applications.
AB  - Natural killer (NK) cells represent a key component of innate immunity. The
      utility of mouse models to recapitulate the human immune response has been a
      matter of ongoing debate, especially with regard to NK cells. However, mouse
      models of NK cells have provided significant advancements in our understanding of
      the biology of the cells that bridge these species. Initial characterization of
      NK cell activity was in mouse hematopoietic stem cell transplantation models.
      Recent findings include uncovering functionally disparate subsets of NK cells
      based on unique inhibitory receptor expression patterns, the existence of memory
      like NK cells, and immunoregulatory NK cells that affect hematopoiesis and T-cell
      function. In addition, the biology of these cells with regard to MHC-binding
      receptors that affect NK cell subset maturation and function in the context of
      licensing, the importance of cytokines such as IL-15 in their development and
      maintenance, and evidence of NK exhaustion have been initially studied in mice.
      Many of these findings have been validated in clinical studies and demonstrate
      the significant wealth of knowledge that can be obtained by mouse models.
      However, it is important to understand the limitations and conditions of the
      mouse models, particularly when studying NK cells in hematopoietic stem cell
      transplantation and cancer. 

PMID- 24319184
TI  - FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013?
AB  - Patients with acute myeloid leukemia who harbor an FMS-like tyrosine kinase 3
      (FLT3) mutation present several dilemmas for the clinician. The results of an
      FLT3 mutation test, which can be influenced by several variables, need to be
      interpreted according to the clinical setting and there is a need for
      internationally standardized FLT3 mutation assays. Because of the lack of
      prospective studies, the role of allogeneic transplantation as consolidation
      therapy is still somewhat controversial, but the preponderance of evidence
      suggests that transplantation in first remission, if possible, is probably the
      best option. Clinically useful FLT3 inhibitors are hopefully on the near horizon
      and are being studied in the context of current treatment paradigms. 

PMID- 24319186
TI  - Bringing natural killer cells to the clinic: ex vivo manipulation.
AB  - Recently, there has been a substantial gain in our understanding of the role that
      natural killer (NK) cells play in mediating innate host immune responses against
      viruses and cancer. Although NK cells have long been known to be capable of
      killing cancer cells independently of antigen recognition, the full therapeutic
      potential of NK cell-based immunotherapy has yet to be realized. Here we review
      novel methods to activate and expand human NK cells ex vivo for adoptive transfer
      in humans, focusing on the important phenotypic and functional differences
      observed among freshly isolated, cytokine activated, and ex vivo-expanded NK
      populations. 

PMID- 24319187
TI  - Therapeutic applications: natural killer cells in the clinic.
AB  - Natural killer (NK) cells recognize targets stressed by malignant transformation
      or infection (particularly CMV). We now know that NK cells can be long-lived and
      remember past exposures. They become educated by interaction with MHC class I
      molecules to gain potent function to kill targets and produce cytokines. In the
      clinical setting, haploidentical NK cells can be transferred adoptively to treat
      cancer. Persistence and in vivo expansion of NK cells depends on lymphodepleting
      chemotherapy to make space for the release of endogenous IL-15. In vivo expansion
      is also enhanced by cytokine administration. IL-2 has been used at low doses to
      stimulate NK cells in vivo, but has the down side of stimulating CD25hi
      regulatory T cells. IL-15 is now being tested and has the advantage of avoiding
      inhibitory regulatory T cell stimulation. In refractory acute myeloid leukemia,
      leukemia clearance is correlated with the persistence and in vivo expansion of NK
      cells after adoptive transfer. Limitations to NK cell therapy include poor in
      vivo survival and lack of specificity. Monoclonal antibodies and bispecific or
      trispecific killer engagers to target CD16 on NK cells to enhance recognition of
      various tumor antigens and ADAM17 inhibition to prevent CD16 shedding after NK
      cell activation should promote enhanced killing of cancer with specificity.
      Future strategies to exploit favorable donor immunogenetics or to expand NK cells
      ex vivo from blood, progenitors, or pluripotent progenitors may overcome immune
      barriers of adoptive transfer and comparative clinical trials will be needed to
      test these approaches.

PMID- 24319188
TI  - von Willebrand disease: advances in pathogenetic understanding, diagnosis, and
      therapy.
AB  - von Willebrand disease (VWD) is the most common autosomally inherited bleeding
      disorder. The disease represents a range of quantitative and qualitative
      pathologies of the adhesive glycoprotein von Willebrand factor (VWF). The
      pathogenic mechanisms responsible for the type 2 qualitative variants of VWF are
      now well characterized, with most mutations representing missense substitutions
      influencing VWF multimer structure and interactions with platelet GPIbalpha and
      collagen and with factor VIII. The molecular pathology of type 3 VWD has been
      similarly well characterized, with an array of different mutation types producing
      either a null phenotype or the production of VWF that is not secreted. In
      contrast, the pathogenetic mechanisms responsible for type 1 VWD remain only
      partially resolved. In the hemostasis laboratory, the measurement of VWF:Ag and
      VWF:RCo are key components in the diagnostic algorithm for VWD, although the
      introduction of direct GPIbalpha-binding assays may become the functional assay
      of choice. Molecular genetic testing can provide additional benefit, but its
      utility is currently limited to type 2 and 3 VWD. The treatment of bleeding in
      VWD involves the use of desmopressin and plasma-derived VWF concentrates and a
      variety of adjunctive agents. Finally, a new recombinant VWF concentrate has just
      completed clinical trial evaluation and has demonstrated excellent hemostatic
      efficacy and safety. 

PMID- 24319189
TI  - The hemophilias and their clinical management.
AB  - Outcomes for patients with hemophilia have improved dramatically over the past 50
      years. With the increased availability of safe clotting factor concentrates, the
      primary focus in clinical management is now the prevention of long-term
      complications, most notably the debilitating hemophilic arthropathy that is
      associated with severe disease. This article reviews evidence-based approaches
      for managing both children and adults with hemophilia. Definitive evidence of
      improved clinical results from primary prophylaxis started in young patients with
      severe hemophilia A and a minimal bleeding history is presented. Furthermore,
      recent studies showing benefits for initiating prophylaxis in older adolescents
      and adults with established joint disease are examined. Inhibitors to factor VIII
      are the most problematic complication of factor replacement therapy. Patient
      specific and treatment-related factors that contribute to the risk of inhibitor
      formation are discussed and controversies and clinical evidence related to
      approaches for tolerance induction are reviewed. 

PMID- 24319190
TI  - Inherited platelet disorders including Glanzmann thrombasthenia and Bernard
      Soulier syndrome.
AB  - Inherited platelet disorders (IPDs) are a heterogeneous group of diseases
      affecting platelet production, morphology, and function. The degree of
      thrombocytopenia and functional abnormality of platelets determines the clinical
      manifestations. Although severe deficiencies may cause excessive bleeding
      beginning in early childhood, most of IPDs have mild bleeding tendencies and
      therefore are not always easy to distinguish from acquired platelet disorders.
      The diagnosis of IPD may require extensive laboratory investigation, because
      current routine laboratory tests are not satisfactory for differential diagnosis
      in some cases, and most of the specific tests are not readily available in many
      countries. This review summarizes the classification and clinical and molecular
      characteristics of known IPDs, including Bernard-Soulier syndrome and Glanzmann
      thrombasthenia, with a focus on current challenges in the laboratory diagnosis
      and management of bleeding in these patients. 

PMID- 24319191
TI  - Current management of immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune-mediated condition that results
      from antibody-mediated destruction of platelets and impaired megakaryocyte
      platelet production. ITP patients exhibit severe thrombocytopenia and are at risk
      for significant hemorrhage. Few randomized trials exist to guide management of
      patients with ITP. Ultimately, each patient requires an individualized treatment
      plan that takes into consideration the platelet count, bleeding symptoms, health
      related quality of life, and medication side effects. This article provides an up
      to-date review of management strategies drawing on links between the expanding
      amounts of clinical trial data and associated biology studies to enhance
      understanding of the disease heterogeneity with regard to the complex
      pathogenesis and response to treatment. 

PMID- 24319192
TI  - Is anti-D immunoglobulin still a frontline treatment option for immune
      thrombocytopenia?
AB  - A 5-year-old boy presents with platelet count of 2*10(9)/L and clinical and
      laboratory evidence of immune thrombocytopenia. He has epistaxis and oral mucosal
      bleeding. Complete blood count reveals isolated thrombocytopenia without any
      decline in hemoglobin and he is Rh+. You are asked if anti-D immunoglobulin is an
      appropriate initial therapy for this child given the 2010 Food and Drug
      Administration "black-box" warning.

PMID- 24319193
TI  - Current consideration and management of disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (DIC) is a devastating clinical condition
      that is characterized by the loss of normal hemostatic control in response to
      sustained and systemic cell injury. The inciting injury may be from infection,
      trauma, or malignancy, but the consequent pathophysiology is multifactorial
      involving intertwined feedback loops between the coagulant, immune, and
      inflammatory pathways. Central to this is thrombin generation, but the ubiquitous
      nature of its in vivo functional consequences can make it difficult to dissect
      away the separate but overlapping components to the clinical problem. Therefore,
      early recognition and resolution of the precipitating events leading to DIC
      remains the central tenet to clinical care. This article refreshes our conceptual
      understanding of DIC pathogenesis and draws in recent advances in the cycle of
      cell death caused by extracellular nuclear proteins. It also aims to delineate
      recognition of response pathways that can be predominantly procoagulant or
      profibrinolytic to enable a more personalized and evidence-based approach to be
      delivered to the patient with DIC. 

PMID- 24319194
TI  - Thrombotic thrombocytopenic purpura: basic pathophysiology and therapeutic
      strategies.
AB  - VWF is a multimeric plasma glycoprotein that specifically recruits platelets to
      sites of vessel injury. VWF multimeric size is central to this function, with
      larger multimers being more hemostatically active. Regulation of VWF multimeric
      size is mediated by the plasma metalloprotease ADAMTS13 (A Disintegrin And
      Metalloproteinase with ThromboSpondin type 1 motifs, member 13). This enzyme can
      only recognize and cleave VWF when it is unraveled by rheological shear forces of
      the flowing blood. After the exposure of cryptic exosites, VWF recognition by
      ADAMTS13 involves multiple interactions that enable the protease to cleave VWF.
      Loss of VWF multimer size regulation caused by severe ADAMTS13 deficiency (either
      inherited or acquired) is associated with the microvascular thrombotic disorder
      thrombotic thrombocytopenic purpura (TTP). The sequelae associated with TTP are
      widely thought to be linked to hyperreactive circulating VWF that cause unwanted
      platelet aggregation in the high shear environment of the microvasculature.
      Diagnosis of TTP is primarily made through a combination of symptoms, analysis of
      plasma ADAMTS13 activity, and detection of inhibitory anti-ADAMTS13 antibodies.
      Current frontline treatments for TTP include plasma exchange, which serves to
      remove inhibitory antibodies (in acquired TTP) and provide a source of functional
      ADAMTS13, and steroids to treat the autoimmune component of acquired TTP. The use
      of anti-CD20 therapy has also exhibited encouraging results in the treatment of
      acquired TTP. Newer therapeutic strategies that are currently being explored or
      are in development include recombinant ADAMTS13, a hyperreactive ADAMTS13
      variant, and anti-VWF therapy. This review discusses the basic biochemistry of
      VWF and ADAMTS13, their dysfunction in TTP, and therapeutic approaches for the
      amelioration of TTP. 

PMID- 24319195
TI  - Drug discovery in academic institutions.
AB  - Although academic science has always provided a fundamental understanding of the
      biological and clinical basis of disease, the opportunity and imperative for
      academics to contribute more directly to the discovery of new medicines continues
      to grow. Embedding medicinal chemists with cancer biologists creates
      collaborative opportunities for drug discovery and the design and synthesis of
      chemical biology tool compounds (chemical probes) to better elucidate the role of
      specific proteins and pathways in biology and disease. Two case studies are
      presented here: (1) the discovery of inhibitors of mer kinase to treat acute
      lymphoblastic leukemia in children and (2) the discovery of chemical probes
      targeting epigenetic regulators. These case studies provide lessons in target
      selection strategies, the requirement for iterative optimization of lead
      compounds (useful drugs/probes rarely come directly from a screen), and the value
      of mutually dependent collaborations between medicinal chemists and cancer
      biologists. 

PMID- 24319196
TI  - Antibody-drug conjugates: the chemistry behind empowering antibodies to fight
      cancer.
AB  - For more than a century, the concept of a "magic bullet" to deliver cytotoxic
      therapy to the site of disease has been envisioned but only recently have
      technological advances enabled antibody-drug conjugates to fulfill that dream.
      The recent approvals of brentuximab vedotin and ado-trastuzumab emtansine and
      emerging data for many molecules in clinical trials highlight the potential for
      antibody-drug conjugates to offer new therapeutic options for patients. This
      chapter reviews the evolution, state of the art, and potential future
      improvements that are enabling rapid development of this important class of
      cancer therapeutics. 

PMID- 24319197
TI  - Opening up drug development to everyone.
AB  - Effective drug therapies are a cornerstone of medical practice. The path from
      drug discovery to approval is expensive and commonly associated with failure. The
      cost of drug development exceeds 800 million dollars per product. Late failure
      due to lack of clinical efficacy is a common cause of high costs. Recent attempts
      to improve the process of drug development involve the formation of public
      private partnerships, which are facilitating the creation of new collaborations
      among corporate and nonprofit entities to find solutions that will accelerate
      innovative drug discovery. 

PMID- 24319198
TI  - ABCs of genomics.
AB  - Our genome, the 6 billion bp of DNA that contain the blueprint of a human being,
      has become the focus of intense interest in medicine in the past two decades. Two
      developments have contributed to this situation: (1) the genetic basis of more
      and more diseases has been discovered, especially of malignant diseases, and (2)
      at the same time, our abilities to analyze our genome have increased
      exponentially through technological breakthroughs. We can expect genomics to
      become ever more relevant for day-to-day treatment decisions and patient
      management. It is therefore of great importance for physicians, especially those
      who are treating patients with malignant diseases, to become familiar with our
      genome and the technologies that are currently available for genomics analysis.
      This review provides a brief overview of the organization of our genome, high
      throughput sequence analysis methods, and the analysis of leukemia genomes using
      next-generation sequencing (NGS) technologies. 

PMID- 24319199
TI  - Genomic applications in the clinic: use in treatment paradigm of acute myeloid
      leukemia.
AB  - In recent years, research in genomics has resulted in the rapid uncovering of the
      molecular pathogenesis of acute myeloid leukemia (AML). The identification of the
      genetic determinants of response to standard-but also to experimental-treatment
      is increasingly used for patient counseling, to guide clinical decision making,
      and for resource-efficient care provision at diagnosis, during consolidation
      treatment and follow-up, and after relapse. Gene mutations now allow us to
      explore the enormous diversity among cytogenetically defined subsets of AML, in
      particular the large subset of cytogenetically normal AML. Nonetheless, there are
      several challenges in evaluating the prognostic value of a specific mutation in
      the concert of the various concurrent mutations and determining the relative
      prognostic value of the genetic profile during the disease course. In particular,
      changes in the genetic profile in relapse compared with that at diagnosis will
      increasingly affect the treatment strategy at relapse, but also will give us the
      possibility of learning which treatment strategy during frontline therapy is best
      to prevent them. 

PMID- 24319200
TI  - Genomic stratification for the treatment of lymphomas.
AB  - The application of high-throughput genomic approaches in lymphomas has generated
      a wealth of data regarding the molecular underpinnings of these cancers. In this
      review, key findings from recent studies are discussed, as well as the genetic
      heterogeneity that underlies common lymphomas including diffuse large B-cell
      lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia, and the
      implications for identifying new therapeutic opportunities and personalized
      medicine. 

PMID- 24319201
TI  - Natural killer cells and regulatory T cells: how to manipulate a graft for
      optimal GVL.
AB  - Two of the major complications that limit the efficacy of allogeneic
      hematopoietic cell transplantation (allo-HCT) are disease relapse and GVHD. Due
      to their rapid recovery early after allo-HCT and their ability to kill malignant
      targets without prior exposure, natural killer (NK) cells have been considered
      one of the main effector cells that mediate early GVL reactions. Conversely,
      regulatory T ells (Tregs) have proven to be critical in facilitating self
      tolerance. Both murine and human studies have demonstrated a significant role for
      Tregs in the modulation of GVHD after allo-HCT. This article reviews the
      mechanisms of how these 2 cell types carry out these functions, focusing on the
      post-allo-HCT period. Surprisingly, relatively few studies have addressed how
      Tregs and NK cells interact with one another and whether these interactions are
      antagonistic. Although preclinical studies suggest active cross-talk between NK
      cells and Tregs, early clinical studies have not shown a detrimental impact of
      Treg therapy on relapse. Despite this, interruption of tolerogenic signals may
      enhance the efficacy of NK effector functions. Methods to transiently impair Treg
      functions and augment NK cell alloreactivity will be discussed. 

PMID- 24319202
TI  - T-cell therapy for viral infections.
AB  - Viral infections remain a major cause of morbidity in patients with
      immunodeficiency, such as recipients of hemopoietic stem cell transplantation.
      Adoptive transfer of donor-derived virus-specific cytotoxic T lymphocytes is a
      strategy to restore virus-specific immunity to prevent or treat viral diseases
      and has been tested in the clinical setting for more than 20 years. Several
      different groups have used expanded virus-specific T-cell products specific for
      one or multiple viruses to both reconstitute antiviral immunity after
      transplantation and to treat active viral infections. Response rates are
      encouraging, although resistance has been seen when the infused cell population
      has had restricted specificity or has targeted antigens expressed in donor
      infected but not virally infected recipient cells. The goal of current trials is
      to make this approach more broadly applicable using more rapidly available
      products from the donor, such as directly selected or briefly expanded cells or
      closely matched banked cells. 

PMID- 24319203
TI  - T-cell adoptive immunotherapy for acute lymphoblastic leukemia.
AB  - Substantial progress has been made in the treatment of precursor B-cell acute
      lymphoblastic leukemia (B-ALL), but recurrent disease remains a leading cause of
      death in children due to cancer and outcomes for adults with B-ALL remain poor.
      Recently, complete clinical responses have been observed in small numbers of
      patients with B-ALL treated with adoptive immunotherapy using T cells genetically
      engineered to express chimeric antigen receptors (CARs) targeting CD19, a cell
      surface molecule present in essentially all cases of B-ALL. Preclinical data
      suggest that CARs targeting CD22, another antigen present in the majority of B
      ALL cases, are similarly potent. Several clinical studies already under way will
      soon more clearly define the rate of response to this novel therapy in B-ALL.
      Further work is needed to identify optimal platforms for CAR-based adoptive
      immunotherapy for leukemia, to establish guidelines for managing toxicity, and to
      determine whether the remissions induced by this approach can be rendered
      durable. 

PMID- 24319204
TI  - Genetic association studies in beta-hemoglobinopathies.
AB  - Characterization of the molecular basis of the beta-thalassemias and sickle cell
      disease (SCD) clearly showed that individuals with the same beta-globin genotypes
      can have extremely diverse clinical severity. Two key modifiers, an innate
      ability to produce fetal hemoglobin and coinheritance of alpha-thalassemia, both
      derived from family and population studies, affect the pathophysiology of both
      disorders at the primary level. In the past 2 decades, scientific research had
      applied genetic approaches to identify additional genetic modifiers. The review
      summarizes recent genetic studies and key genetic modifiers identified and traces
      the story of fetal hemoglobin genetics, which has led to an emerging network of
      globin gene regulation. The discoveries have provided insights on new targets for
      therapeutic intervention and raise possibilities of developing fetal hemoglobin
      predictive diagnostics for predicting disease severity in the newborn and for
      integration into prenatal diagnosis to better inform genetic counseling. 

PMID- 24319205
TI  - Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted
      therapies.
AB  - Recurrent and unpredictable episodes of vaso-occlusion are the hallmark of sickle
      cell disease. Symptomatic management and prevention of these events using the
      fetal hemoglobin-reactivating agent hydroxyurea are currently the mainstay of
      treatment. Discoveries over the past 2 decades have highlighted the important
      contributions of various cellular and soluble participants in the vaso-occlusive
      cascade. The role of these elements and the opportunities for therapeutic
      intervention are summarized in this review. 

PMID- 24319206
TI  - Allogeneic transplantation strategies including haploidentical transplantation in
      sickle cell disease.
AB  - Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Despite
      antenatal counseling and neonatal screening programs implemented in higher income
      countries, SCD is still associated with multiple morbidities and early mortality.
      To date, the only curative approach to SCD is hematopoietic stem cell
      transplantation, but this therapy is not yet established worldwide. The
      registries of the European Blood and Marrow Transplant (EBMT) and the Centre for
      International Blood and Marrow Transplant Research (CIBMTR) account,
      respectively, for 611 and 627 patients receiving transplantations for SCD. Most
      of these patients were transplanted with grafts from an HLA-identical sibling
      donor. The main obstacles to increasing the number of transplantations are a lack
      of awareness on the part of physicians and families, the absence of reliable
      prognostic factors for severity, and the perceived risk that transplantation
      complications may outweigh the benefits of early transplantation. Results show
      that more than 90% of patients having undergone an HLA-identical sibling
      transplantation after myeloablative conditioning are cured, with very limited
      complications. Major improvement is expected from the use of new reduced-toxicity
      conditioning regimens and the use of alternative donors, including unrelated cord
      blood transplantations and related haploidentical bone marrow or peripheral blood
      stem cell transplantations. 

PMID- 24319207
TI  - Pathogenesis and clinical implications of HIV-related anemia in 2013.
AB  - Anemia is a common feature of HIV-related disease and has been uniformly
      demonstrated to be an independent predictor of morbidity and mortality. Although
      anemia often responds to combination antiretroviral therapy, many patients remain
      anemic despite therapy and such persistent anemia continues to negatively affect
      prognosis regardless of drug response. Anemia is also a common feature of normal
      aging. We postulate that the pathophysiology of anemia in HIV, especially that
      which persists in the face of combination antiretroviral therapy, is a reflection
      of underlying proinflammatory pathways that are also thought to contribute to
      anemia in the elderly, as well as other age-related chronic diseases such as
      cardiovascular disease and chronic obstructive pulmonary disease. This suggests
      that HIV induces inflammatory pathways that are associated with a pattern of
      accelerated aging and that anemia is a biomarker of these processes. A better
      understanding of the pathophysiology of HIV-related anemia may provide important
      entry points for improving the chronic manifestations of HIV-related disease. 

PMID- 24319208
TI  - Update on the treatment of HIV-associated hematologic malignancies.
AB  - HIV is associated with an excess cancer risk, particularly of lymphoid
      malignancies. Modern therapeutics has changed the landscape of HIV disease and
      typical opportunistic complications of AIDS are now largely avoided. Although the
      risk of lymphoma has decreased, it still remains high. Nevertheless, treatment
      outcomes have improved due both to improvements in HIV medicine and in cancer
      therapeutics for the common lymphomas occurring in those with HIV infection.
      Other hematologic malignancies are rarely seen in HIV-infected patients, but the
      standardized risk ratio for many of these cancers is higher than in the
      background population. Principles of cancer care and appreciation for HIV
      infection as a comorbid condition can guide physicians in setting realistic goals
      and treatment for this patient population. In many cases, expected outcomes are
      very similar to the HIV-unrelated patients and therapeutic planning should be
      based on this understanding. Treatment tolerance can be predicted based on the
      status of the HIV disease and the cancer therapy being administered. For those
      hematologic cancers in which transplantation is part of standard care, this
      modality should be considered an option in those with HIV infection. 

PMID- 24319209
TI  - Transplantation in HIV-infected subjects: is cure possible?
AB  - With the advent of effective antiretroviral therapy, the treatment of patients
      with HIV-related malignancies, especially lymphoma, has greatly improved,
      yielding results comparable to those seen in patients with lymphoma unrelated to
      HIV. The platform of transplantation of hematopoietic stem cells has facilitated
      studies of genetically modified stem cells engineered to express antiretroviral
      genes to resist infection by the HIV virus, testing the concept that engraftment
      of these cells will lead to HIV resistance and elimination of the reservoir of
      virus in the body. Results in patients with HIV and lymphoma have now led to
      studies that will test these principles in HIV patients without concomitant
      malignancy. In addition, in a patient with HIV and acute myeloid leukemia, the
      success of an allogeneic transplantation from an unrelated donor carrying a
      mutation in the CCR5 genes has demonstrated that, in principle, such an approach
      could also lead to cure of patients with HIV. Case studies in HIV patients with
      leukemia undergoing allogeneic transplantation also suggest that there may be a
      therapeutic effect on the HIV reservoir that could alter the natural history of
      HIV in the allogeneic setting. 

PMID- 24319210
TI  - Novel therapy for Hodgkin lymphoma.
AB  - The treatment of Hodgkin lymphoma (HL) relies on multimodality treatment with
      standard chemotherapy, radiation therapy, and autologous or allogeneic stem cell
      transplantation in cases of relapsed disease. Genomic advances in HL provided
      insights into deregulation of key nodal signaling pathways, including the PI3K,
      NF-kappaB, and JAK/STAT pathways, which are amenable to small-molecule targeting.
      Understanding how HL cells interact and depend on their microenvironment for
      survival signals and immune protection may uncover other such pathways. Small
      molecule targeting has the potential to dramatically improve treatment outcomes,
      especially in patients with highly refractory disease and those with poor
      tolerance to existing chemotherapies. As novel therapies continue to be developed
      for HL, the challenge will be to address the needs of high-risk groups, reduce
      long-term therapy-related morbidity, position current established treatments with
      novel therapies, and concurrently develop biomarkers to aid in patient selection.
      Brentuximab vedotin, which was approved in 2011, is already shifting the
      treatment paradigm of HL. Undoubtedly, other novel therapeutics in the pipeline
      will affect positively the landscape of treatment in HL. 

PMID- 24319211
TI  - Management of early-stage Hodgkin lymphoma: is there still a role for radiation?
AB  - Although radiotherapy is highly effective for the treatment of Hodgkin lymphoma,
      the realization of its potential long-term toxicity and the demonstration of
      excellent results from combination chemotherapy have led to a retreat from its
      use in early-stage disease. Recent trials using functional imaging may allow
      better identification of those patients for whom radiotherapy may be safely
      omitted without compromising cure rates and this review examines the evidence for
      this. 

PMID- 24319212
TI  - Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment?
AB  - Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique diagnostic
      entity, with only ~500 new cases in the United States per year with a similar
      infrequent incidence worldwide. NLPHL also has distinctive pathobiology and
      clinical characteristics compared with the more common classical Hodgkin lymphoma
      (cHL), including CD20 positivity of the pathognomic lymphocytic and histiocytic
      cells and an overall more indolent course with a higher likelihood of delayed
      relapses. Given the limited numbers of prospective NLPHL-focused trials,
      management algorithms historically have typically been centered on retrospective
      data with guidelines often adopted from cHL and indolent B-cell lymphoma
      treatment approaches. Key recent publications have delineated that NLPHL has a
      higher level of pathological overlap with cHL and the aggressive B-cell lymphomas
      than with indolent B-cell lymphomas. Over the past decade, there has been a
      series of NLPHL publications that evaluated the role of rituximab in the
      frontline and relapsed setting, described the relative incidence of
      transformation to aggressive B-cell lymphomas, weighed the benefit of addition of
      chemotherapy to radiation treatment for patients with early-stage disease,
      considered what should be the preferred chemotherapy regimen for advanced-stage
      disease, and even assessed the potential role of autologous stem cell
      transplantation for the management of relapsed disease. General themes within the
      consensus guidelines include the role for radiation treatment as a monotherapy
      for early-stage disease, the value of large B-cell lymphoma-directed regimens for
      transformed disease, the utility of rituximab for treatment of relapsed disease,
      and, in the pediatric setting, the role of surgical management alone for patients
      with early-stage disease.

PMID- 24319213
TI  - Evidence-based approach to treatment of febrile neutropenia in hematologic
      malignancies.
AB  - Applying the principles of evidence-based medicine to febrile neutropenia (FN)
      results in a more limited set of practices than expected. Hundreds of studies
      over the last 4 decades have produced evidence to support the following: (1) risk
      stratification allows the identification of a subset of patients who may be
      safely managed as outpatients given the right health care environment; (2)
      antibacterial prophylaxis for high-risk patients who remain neutropenic for >=7
      days prevents infections and decreases mortality; (3) the empirical management of
      febrile neutropenia with a single antipseudomonal beta-lactam results in the same
      outcome and less toxicity than combination therapy using aminoglycosides; (4)
      vancomycin should not be used routinely empirically either as part of the initial
      regimen or for persistent fever, but rather should be added when a pathogen that
      requires its use is isolated; (5) empirical antifungal therapy should be added
      after 4 days of persistent fever in patients at high risk for invasive fungal
      infection (IFI); the details of the characterization as high risk and the choice
      of agent remain debatable; and (6) preemptive antifungal therapy in which the
      initiation of antifungals is postponed and triggered by the presence, in addition
      to fever, of other clinical findings, computed tomography (CT) results, and
      serological tests for fungal infection is an acceptable strategy in a subset of
      patients. Many practical management questions remain unaddressed.

PMID- 24319215
TI  - Multidrug-resistant bacteria: what is the threat?
AB  - Despite big advances in antimicrobial therapies and infection strategies, the
      emergence of antibiotic resistance represents an emergency situation, especially
      in immunocompromised hosts. Specifically, infections due to multidrug resistant,
      gram-negative pathogens are responsible for high mortality rates and may leave
      few effective antimicrobial options. Furthermore, although new compounds are
      available for severe methicillin-resistant staphylococcal infections, there is a
      paucity of novel classes of antimicrobials to target resistant gram-negatives. A
      careful assessment of the clinical conditions and underlying comorbidities, along
      with knowledge about the previous history of colonization or infections due to
      multidrug-resistant bacteria, represent key points in approaching the
      hematological patient with signs of infection. A de-escalation therapy with
      initial use of wide-spectrum antimicrobials followed by a reassessment after 72
      hours of treatment may represent a good option in severe infections if a
      resistant pathogen is suspected. Prompt empiric or targeted therapy using
      combination regimens (ie, antipseudomonal beta-lactam plus an aminoglycoside or a
      quinolone) with the addition of colistin, along with increased dosage and
      therapeutic drug monitoring, represent options for these life-threatening
      infections. Continuous epidemiological surveillance of local bacteremias is
      necessary, along with stringent enforcement of antibiotic stewardship programs in
      cancer patients. 

PMID- 24319214
TI  - Treatment of fungal disease in the setting of neutropenia.
AB  - Invasive fungal infections are important causes of morbidity and attributable
      mortality in neutropenic patients with hematological malignancies,
      myelodysplasia, and aplastic anemia. Successful risk-based strategies can be
      implemented for prophylaxis, empirical therapy, and preemptive therapy for the
      prevention and early treatment of invasive fungal infections in neutropenic
      hosts. The use of echinocandins for invasive candidiasis and voriconazole for
      invasive aspergillosis has significantly improved outcome. Recent studies
      demonstrate, however, that resistant fungal pathogens may emerge during the
      course of these antifungal interventions. Although triazole-resistant Candida
      spp. have been well described as causes of breakthrough candidemia, other
      organisms now pose a similar threat. Such organisms include echinocandin
      resistant Candida glabrata and Candida parapsilosis species complex. The
      Mucorales, Fusarium spp., and Scedosporium spp. may emerge in the setting of
      voriconazole prophylaxis. The challenges of these emerging pathogens underscore
      the need for the development of new antifungal agents and strategies. 

PMID- 24319216
TI  - Sickle cell disease pain management and the medical home.
AB  - Pain is the most common cause for hospitalization and acute morbidity in sickle
      cell disease (SCD). The consequences of SCD-related pain are substantial,
      affecting both the individual and the health care system. The emergence of the
      patient-centered medical home (PCMH) provides new opportunities to align efforts
      to improve SCD management with innovative and potentially cost-effective models
      of patient-centered care. The Department of Health and Human Services has
      designated SCD as a priority area with emphasis on creating PCMHs for affected
      patients. The question for patients, clinicians, scientists, and policy-makers is
      how the PCMH can be designed to address pain, the hallmark feature of SCD. This
      article provides a framework of pain management within the PCMH model. We present
      an overview of pain and pain management in SCD, gaps in pain management, and
      current care models used by patients and discuss core PCMH concepts and
      multidisciplinary team-based PCMH care strategies for SCD pain management. 

PMID- 24319217
TI  - Transfusion therapy for sickle cell disease: a balancing act.
AB  - Transfusion therapy is a key intervention in decreasing morbidity and mortality
      in patients with sickle cell disease (SCD). Current indications for acute and
      chronic transfusion therapy have significantly increased the number of RBC units
      transfused to patients with SCD worldwide. This review summarizes transfusion
      management for the treatment or prevention of neurologic and perioperative
      complications, acute chest syndrome, and acute anemia associated with SCD.
      Despite the recognized benefits of transfusion therapy, it is not without the
      risks of iron overload, alloimmunization, and delayed hemolytic transfusion
      reactions. Transfusional iron overload management includes automated RBC
      exchange, noninvasive imaging to monitor iron burden, and iron chelation with
      parenteral or oral agents. Although limited and extended RBC antigen matching
      reduces antibody formation, the prevalence of RBC alloimmunization in patients
      with SCD remains high. Recent studies demonstrate that RH genetic diversity in
      patients with SCD contributes to Rh alloimmunization, suggesting that even more
      refined RBC matching strategies are needed. Advances in molecular blood group
      typing offer new opportunities to improve RBC matching of donors and recipients
      and can be of particular benefit to patients with SCD. 

PMID- 24319218
TI  - Consequences and management of iron overload in sickle cell disease.
AB  - The aims of this review are to highlight the mechanisms and consequences of iron
      distribution that are most relevant to transfused sickle cell disease (SCD)
      patients and to address the particular challenges in the monitoring and treatment
      of iron overload. In contrast to many inherited anemias, in SCD, iron overload
      does not occur without blood transfusion. The rate of iron loading in SCD depends
      on the blood transfusion regime: with simple hypertransfusion regimes, rates
      approximate to thalassemia major, but iron loading can be minimal with automated
      erythrocyte apheresis. The consequences of transfusional iron overload largely
      reflect the distribution of storage iron. In SCD, a lower proportion of
      transfused iron distributes extrahepatically and occurs later than in thalassemia
      major, so complications of iron overload to the heart and endocrine system are
      less common. We discuss the mechanisms by which these differences may be
      mediated. Treatment with iron chelation and monitoring of transfusional iron
      overload in SCD aim principally at controlling liver iron, thereby reducing the
      risk of cirrhosis and hepatocellular carcinoma. Monitoring of liver iron
      concentration pretreatment and in response to chelation can be estimated using
      serum ferritin, but noninvasive measurement of liver iron concentration using
      validated and widely available MRI techniques reduces the risk of under- or
      overtreatment. The optimal use of chelation regimes to achieve these goals is
      described. 

PMID- 24319219
TI  - The diagnosis and treatment of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common condition that can lead to complications
      such as postphlebitic syndrome, chronic pulmonary artery hypertension, and death.
      The approach to the diagnosis of has evolved over the years and an algorithm
      strategy combining pretest probability, D-dimer testing, and diagnostic imaging
      now allows for safe, convenient, and cost-effective investigation of patients.
      Patients with low pretest probability and a negative D-dimer can have VTE
      excluded without the need for imaging. The mainstay of treatment of VTE is
      anticoagulation, whereas interventions such as thrombolysis and inferior vena
      cava filters are reserved for special situations. Low-molecular-weight heparin
      has allowed for outpatient management of most patients with deep vein thrombosis
      at a considerable cost savings to the health care system. Patients with
      malignancy-associated VTE benefit from decreased recurrent rates if treated with
      long-term low-molecular-weight heparin. The development of new oral
      anticoagulants further simplifies treatment. The duration of anticoagulation is
      primarily influenced by underlying cause of the VTE (whether provoked or not) and
      consideration of the risk for major hemorrhage. Testing for genetic and acquired
      thrombophilia may provide insight as to the cause of a first idiopathic deep vein
      thrombosis, but the evidence linking most thrombophilias to an increased risk of
      recurrent thrombosis is limited. 

PMID- 24319220
TI  - Pros and cons of new oral anticoagulants.
AB  - The availability of new oral anticoagulants (NOACs) targeting either thrombin
      (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention
      and treatment of thrombosis has been highly anticipated. NOACs have major
      pharmacologic advantages over vitamin K antagonists (eg, warfarin), including
      rapid onset/offset of action, few drug interactions, and predictable
      pharmacokinetics, eliminating the requirement for regular coagulation monitoring.
      Regulatory agencies have approved several NOACs for specific indications based on
      the results of clinical trials demonstrating efficacy and safety that are at
      least as good, if not better, than warfarin (for stroke prevention in atrial
      fibrillation and treatment and secondary prevention of venous thromboembolism) or
      low-molecular-weight heparin, which is injectable (for initial treatment of
      venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee
      arthroplasty). However, the adoption of this new therapeutic class into clinical
      practice has been slower than expected due to several factors including concerns
      regarding medication adherence without laboratory monitoring, uncertainty about
      dosing in some patient populations (eg, renal dysfunction, marked extremes of
      body weight), and higher drug costs compared with warfarin. Other issues are the
      current absence of specific antidotes for NOACs and assays to measure drug levels
      at most centers. The indications for NOACs on the market will expand and at least
      one additional agent (edoxaban) will likely gain approval within the next 2
      years. As practitioners gain familiarity with the drugs and healthcare systems
      adapt to their use, NOAC use will increase substantially over time. Warfarin,
      however, will continue to be an appropriate anticoagulant choice for many
      patients. 

PMID- 24319221
TI  - Risk assessment for recurrence and optimal agents for extended treatment of
      venous thromboembolism.
AB  - Venous thromboembolism (VTE) has a variable recurrence rate after the
      discontinuation of anticoagulant treatment. Therefore, the duration of
      anticoagulation therapy after a first VTE should be tailored to the estimated
      risk for recurrence. Anticoagulant therapy should be discontinued after the
      initial 3 to 6 months in those patients who had the first episode in association
      with temporary risk factors. The duration of anticoagulant therapy in patients
      who had a first episode of cancer-associated VTE should be reassessed over time
      based on the persistence of cancer and anticancer therapy. After 3 to 6 months of
      anticoagulant treatment for VTE, patients with a first unprovoked event and an
      estimated low risk for bleeding complications should be evaluated for indefinite
      treatment on an individualized basis. New oral anticoagulants have been evaluated
      for the extended treatment of VTE. Large phase 3 studies have shown that
      dabigatran, rivaroxaban, and apixaban are effective and safe in this indication.
      These agents do not require monitoring for dose adjustment and could make
      extended treatment more feasible and acceptable to patients. 

PMID- 24319222
TI  - Monoclonal gammopathy of undetermined significance and smoldering multiple
      myeloma: biological insights and early treatment strategies.
AB  - After decades of virtually no progress, multiple myeloma survival has improved
      significantly in the past 10 years. Indeed, multiple myeloma has perhaps seen
      more remarkable progress in treatment and patient outcomes than any other cancer
      during the last decade. Recent data show that multiple myeloma is consistently
      preceded by a precursor state (monoclonal gammopathy of undetermined significance
      [MGUS]/smoldering multiple myeloma [SMM]). This observation provides a framework
      for prospective studies focusing on transformation from precursor disease to
      multiple myeloma and for the development of treatment strategies targeting "early
      myeloma." This review discusses current biological insights in MGUS/SMM, provides
      an update on clinical management, and discusses how the integration of novel
      biological markers, molecular imaging, and clinical monitoring of MGUS/SMM could
      facilitate the development of early treatment strategies for high-risk SMM (early
      myeloma) patients in the future. 

PMID- 24319223
TI  - How should we treat newly diagnosed multiple myeloma patients?
AB  - Multiple myeloma (MM) is the second most frequent hematological disease. Two
      thirds of newly diagnosed MM patients are more than 65 years of age. Elsewhere in
      this issue, McCarthy et al discuss the treatment of transplantation candidates;
      this chapter focuses on the data available concerning therapy for non
      transplantation-eligible MM patients. Treatment goals for these non
      transplantation-eligible patients should be to prolong survival by achieving the
      best possible response while ensuring quality of life. Until recently, treatment
      options were limited to alkylators, but new up-front treatment combinations based
      on novel agents (proteasome inhibitors and immunomodulatory drugs) plus
      alkylating agents have significantly improved outcomes. Other nonalkylator
      induction regimens are also available and provide a novel backbone that may be
      combined with novel second- and third-generation drugs. Phase 3 data indicate
      that maintenance therapy or prolonged treatment in elderly patients also improves
      the quality and duration of clinical responses, extending time to progression and
      progression-free survival; however, the optimal scheme, appropriate doses, and
      duration of long-term therapy have not yet been fully determined. The potential
      for novel treatment regimens to improve the adverse prognosis associated with
      high-risk cytogenetic profiles also requires further research. In summary,
      although we have probably doubled the survival of elderly patients, this group
      requires close monitoring and individualized, dose-modified regimens to improve
      tolerability and treatment efficacy while maintaining their quality of life. 

PMID- 24319224
TI  - Strategies for induction, autologous hematopoietic stem cell transplantation,
      consolidation, and maintenance for transplantation-eligible multiple myeloma
      patients.
AB  - There have been major advances in the past decade in the continuum of therapy for
      transplantation-eligible multiple myeloma patients. For patients requiring
      therapy, recommended induction treatment consists of triple drug regimens
      followed by the collection of hematopoietic stem cells. The question of early
      versus delayed transplantation is under investigation and may identify patients
      for whom early transplantation is optimal therapy and those for whom it may be
      delayed. For transplantation-eligible patients, high-dose melphalan remains the
      standard regimen. After transplantation, consolidation can be considered for
      patients with less than a complete remission. Maintenance therapy with bortezomib
      or lenalidomide (or both in very-high-risk patients) is a reasonable option for
      long-term disease control and improvement in overall survival. Incorporation of
      new agents into the continuum of multiple myeloma care should result in improved
      outcomes and long-term disease control. 

PMID- 24319225
TI  - Prognostic models in myelodysplastic syndromes.
AB  - Establishing the prognosis for patients with myelodysplastic syndromes (MDS) is a
      key element of their care. It helps patients understand the severity of their
      disease and set expectations for their future. For physicians, an accurate
      estimate of prognosis drives decisions about the timing and choice of therapeutic
      options to consider. The International Prognostic Scoring System (IPSS) has been
      the standard tool for MDS risk stratification since it was released in 1997. It
      has been used to describe patients in pivotal clinical trials and is a key
      element of practice guidelines. Subsequent changes to the classification scheme
      for MDS and an underestimation of risk in some patients from the low and
      intermediate-1 categories have led to the development of several newer prognostic
      models. The most recent is the revised IPSS (IPSS-R), which addresses several of
      the perceived deficiencies of its predecessor. Despite their utility, none of the
      available prognostic systems incorporates disease-related molecular abnormalities
      such as somatic mutations. These lesions are present in the nearly all cases and
      many have been shown to improve upon existing prognostic models. However, the
      interpretation of somatic mutations can be challenging and it is not yet clear
      how best to combine them with clinical predictors of outcome. Here I review
      several prognostic scoring systems developed after the IPSS and describe the
      emerging use of molecular markers to refine risk stratification in the MDS
      patient population. 

PMID- 24319227
TI  - Who benefits from allogeneic transplantation for myelodysplastic syndromes?: new
      insights.
AB  - Recently, a refined cytogenetic and molecular classification fundamentally
      changed the prognostication of patients with myelodysplastic syndromes (MDS). The
      increasingly complex heterogeneity of this disease entity is mirrored by life
      expectancy rates ranging from almost a decade for very low-risk disease down to
      several months in higher-risk patients, even with conventional treatments.
      Intensive treatment approaches are hampered by the older age of most of the
      patients, potentially leading to an unacceptable adverse event rate. This is
      especially true for allogeneic hematopoietic stem cell transplantation (HCT),
      which, albeit of curative intent, can lead to considerable morbidity and
      mortality mostly as a result of organ toxicity, infectious complications, and
      GVHD. Furthermore, innovative drug developments, including hypomethylating
      agents, have broadened the therapeutic armamentarium and, although not curative,
      can lead to durable responses in subgroups of patients with higher-risk MDS. In
      fact, there is still no prospective randomized trial available that formally
      demonstrates the benefit of allogeneic HCT compared with standard treatments in
      MDS patients. In the absence of randomized data, when considering allogeneic HCT,
      emphasis should be put on patient selection and optimization of the pre- and
      posttransplantation treatment period. In these patients, a thorough comorbidity
      evaluation is mandatory and stratification according to age, cytogenetics,
      cytopenias, disease-related quality of life, and available alternative treatments
      should be performed in deciding whether, when, and how to perform allogeneic HCT.

PMID- 24319226
TI  - Key clinical observations after 5-azacytidine and decitabine treatment of
      myelodysplastic syndromes suggest practical solutions for better outcomes.
AB  - Clinical experience with 5-azacytidine and decitabine treatment of
      myelodysplastic syndromes (MDS), complemented by biological and pharmacological
      studies, has revealed compelling mechanism of action differences compared with
      traditional myeloid cancer treatment mainstays such as cytarabine. For example, 5
      azacytidine and decitabine produce remissions and better overall survival in MDS
      with high-risk chromosome abnormalities at a surprisingly high rate, consistent
      with experimental observations that noncytotoxic DNA methyltransferase depletion
      by 5-azacytidine/decitabine can trigger cell cycle exit independently of p53,
      thus circumventing a basis for resistance to apoptosis-based DNA-damaging
      therapy. That responses cut across the chaotic genomic landscape of MDS
      highlights common threads in disease, such as high expression in myeloblasts of
      differentiation-driving transcription factors yet paradoxical epigenetic
      suppression of proliferation-terminating late-differentiation genes. Less toxic
      regimens (lower dosages but more frequent administration) of 5
      azacytidine/decitabine have been more successful, underscoring the importance of
      preserving functionally normal stem cells, which are rendered more precious by
      attrition from age, previous cytotoxic treatments, and the disease process and
      are needed to relieve cytopenias, the cause of morbidity and mortality. Also
      emphasized is that there can be no therapeutic benefit, regardless of mutation or
      cytogenetic subtype, if DNA methyltransferase is not depleted by sufficient
      overlap between intracellular drug half-lives and S-phase entries of malignant
      cells. Improved understanding of mechanism-of-action differences demands new
      approaches, from historic (but not scientific) more-is-better and one-size-fits
      all empiricism to pharmacodynamic-based designs and combinations directed not
      solely at suppressing malignant clones, but at improving therapeutic indices. 

PMID- 24319228
TI  - JAK inhibition in the myeloproliferative neoplasms: lessons learned from the
      bench and bedside.
AB  - The discovery of the JAK2 V617F mutation in the classic BCR-ABL1-negative
      myeloproliferative neoplasms in 2005 catalyzed a burst of research efforts that
      have culminated in substantial dividends for patients. Beyond JAK2 V617F, a more
      detailed picture of the pathobiologic basis for activated JAK-STAT signaling has
      emerged. In some patients with myelofibrosis (MF), next-generation sequencing
      technologies have revealed a complex clonal architecture affecting both genetic
      and epigenetic regulators of cell growth and differentiation. Although these
      bench-top findings have informed the clinical development of JAK inhibitors in
      MF, they have also provided scientific context for some of their limitations. The
      JAK1/JAK2 inhibitor ruxolitinib is approved for treatment of MF in North America
      and Europe and other lead JAK inhibitors discussed herein (fedratinib
      [SAR302503], momelotinib [CYT387], and pacritinib [SB1518]), have entered
      advanced phases of trial investigation. Uniformly, these agents share the ability
      to reduce spleen size and symptom burden. A major challenge for practitioners is
      how to optimize dosing of these agents to secure clinically relevant and durable
      benefits while minimizing myelosuppression. Suboptimal responses have spurred a
      "return to the bench" to characterize the basis for disease persistence and to
      inform new avenues of drug therapy. 

PMID- 24319229
TI  - Focus on the epigenome in the myeloproliferative neoplasms.
AB  - The discovery of mutations activating JAK-STAT signaling in the majority of
      patients with myeloproliferative neoplasms (MPNs) led to identification of
      tyrosine kinase activation as a predominant mechanism driving MPN pathogenesis.
      Despite this, the existence of additional genetic events that modify the MPN
      phenotype, predate JAK2 mutations, and/or contribute to leukemic transformation
      of MPNs has been suggested. Recently, mutations in several epigenetic modifiers
      have been described in patients with MPNs, including mutations in ASXL1, DNMT3A,
      EZH2, IDH1, IDH2, and TET2. Moreover, the mutant JAK2 itself has been shown
      recently to affect histone posttranslational modifications directly. Here we
      review the biological and clinical implications of epigenetic alterations in the
      pathogenesis of MPNs. 

PMID- 24319230
TI  - Beyond JAK inhibitor therapy in myelofibrosis.
AB  - Myelofibrosis (MF), including primary MF, postpolycythemia vera MF, and
      postessential thrombocythemia MF, is a clonal stem cell disorder characterized by
      BM fibrosis, extramedullary hematopoiesis, and a variable propensity to transform
      into acute leukemia. Allogeneic stem cell transplantation is the only known cure
      for MF, but its applicability is limited by the advanced age of most patients and
      by comorbid conditions. In the past decade, there has been an explosion of
      information on the molecular-genetic features associated with these diseases,
      fueled recently by the discovery of the JAK2V617F mutation. The development of
      JAK inhibitors has represented a significant therapeutic advance for these
      diseases; however, their use in MF has not yet been associated with eradication
      or a significant suppression of the malignant clone. In this era, much remains to
      be understood about MF, but it is likely that the identification of key
      pathogenetic drivers of the disease, coupled with the availability of novel
      molecularly targeted agents, will result in the discovery of new agents that
      significantly alter the natural history of the disease. This review focuses on
      recent and ongoing efforts in the development of novel agents in MF that go
      beyond the field of JAK inhibitors. 

PMID- 24319231
TI  - Targeting B-cell receptor signaling: changing the paradigm.
AB  - It is well known that signals emanating from the B-cell receptor (BCR) activate
      downstream pathways to regulate the development and survival of normal B cells.
      In B-cell malignancies, it is increasingly understood that similar pathways are
      activated through both tonic and chronic active BCR signaling to promote tumor
      viability and resistance to therapy. Recently, several active and oral agents
      have emerged that target key proximal kinases in the BCR pathway, including
      Bruton tyrosine kinase, PI3K, and spleen tyrosine kinase. In early clinical
      studies, these agents have shown significant activity across a broad range of B
      cell lymphomas and chronic lymphocytic leukemia. Especially impressive responses
      have been reported in mantle cell lymphoma and chronic lymphocytic leukemia, and
      many patients remain on treatment with continued disease control. Toxicity
      profiles have been mild in the majority of early studies, without significant
      myelosuppression over prolonged dosing. Due to these attractive attributes,
      several agents targeting the BCR pathway are now entering early combination
      studies with traditional chemotherapeutics and/or other novel agents. It is clear
      that agents targeting the BCR pathway will significantly affect the design of
      future therapeutic regimens for B-cell malignancies. Future research will focus
      on understanding potential mechanisms of resistance, identifying biomarkers of
      response, and defining optimal combination regimens. 

PMID- 24319232
TI  - Dissecting follicular lymphoma: high versus low risk.
AB  - Progress in the management of follicular lymphoma (FL) has translated to improved
      outcomes, with most patients surviving a decade or more from the time of
      diagnosis. However, the disease remains quite heterogeneous and a substantial
      number of patients have more aggressive disease with short responses to therapy
      and/or transformation to higher-grade lymphomas. Given the lack of a single
      standard approach, it is important to understand sources of heterogeneity among
      patients that influence initial management, surveillance strategies, and overall
      prognosis. Most of the validated tools, such as the Follicular Lymphoma
      International Prognostic Index (FLIPI) and FLIPI-2, apply to the frontline
      setting, and there is an unmet need for prognostic tools in relapsed and
      refractory disease states. In particular, the number of prior treatment regimens
      may be less important than the duration of response to the most recent regimen
      and the type of prior therapy received. Furthermore, despite awareness of
      progressive genetic and epigenetic derangements and a growing appreciation of the
      microenvironment's role in FL outcomes, there is no validated means of
      incorporating biologic data into clinical prognostic indices. This review
      highlights the current state of knowledge regarding risk stratification in FL. 

PMID- 24319233
TI  - Transplantation for mantle cell lymphoma: is it the right thing to do?
AB  - Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin lymphoma that is
      both biologically and clinically heterogeneous. A variety of biomarkers, the
      achievement of minimal residual disease negativity after initial therapy, and the
      MCL International Prognostic Index (MIPI) are associated with patient outcome,
      although none has as yet been used for routine treatment stratification. Given
      the lack of widely accepted and standardized treatment approaches, clinical trial
      enrollment should always be considered for the initial therapy of MCL. Outside of
      the trial setting, younger and transplantation-eligible patients with newly
      diagnosed MCL who require treatment should first be considered for a rituximab+a
      high-dose cytarabine-containing regimen, followed by autologous stem cell
      transplantation consolidation in first remission. Symptomatic elderly and
      nontransplantation-eligible individuals typically receive rituximab+bendamustine,
      or R-CHOP (rituximab+cyclophosphamide, hydroxydaunorubicin, vincristine,
      prednisone/prednisolone) followed by maintenance rituximab, the latter a
      treatment plan that has demonstrated extended response duration and survival.
      Promising early results for consolidation approaches with proteasome inhibitors
      and immunomodulatory drugs are now being tested in randomized clinical trials.
      The availability of highly active BCR signaling pathway inhibitors and cell death
      pathway modulation via BH3 mimetics, among other novel agents, promise to rapidly
      expand treatment options, change existing treatment paradigms, and further
      improve outcomes for MCL patients.

PMID- 24319234
TI  - Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and
      classification.
AB  - MYC is a potent oncogene initially identified as the target of the
      t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. MYC gene
      alterations have been identified in other mature B-cell neoplasms that are
      usually associated with an aggressive clinical behavior. Most of these tumors
      originate in cells that do not normally express MYC protein. The oncogenic events
      leading to MYC up-regulation seem to overcome the inhibitory effect of
      physiological repressors such as BCL6 or BLIMP1. Aggressive lymphomas frequently
      carry additional oncogenic alterations that cooperate with MYC dysregulation,
      likely counteracting its proapoptotic function. The development of FISH probes
      and new reliable antibodies have facilitated the study of MYC gene alterations
      and protein expression in large series of patients, providing new clinical and
      biological perspectives regarding MYC dysregulation in aggressive lymphomas. MYC
      gene alterations in large B-cell lymphomas are frequently associated with BCL2 or
      BCL6 translocations conferring a very aggressive behavior. Conversely, MYC
      protein up-regulation may occur in tumors without apparent gene alterations, and
      its association with BCL2 overexpression also confers a poor prognosis. In this
      review, we integrate all of this new information and discuss perspectives,
      challenges, and open questions for the diagnosis and management of patients with
      MYC-driven aggressive B-cell lymphomas. 

PMID- 24319235
TI  - Treatment strategies for aggressive lymphomas: what works?
AB  - Over the past 30 years, many treatment platforms have been developed for diffuse
      large B-cell lymphoma, but none proved better than CHOP (cyclophosphamide,
      hydroxydaunorubicin, vincristine, prednisone/prednisolone). In the
      immunochemotherapy era, however, there is convincing evidence for superior
      chemotherapy platforms. A randomized study from the Groupe d'Etude des Lymphomes
      de l'Adulte showed that R-ACVBP (rituximab plus doxorubicin, cyclophosphamide,
      vindesine, bleomycin, prednisone) was superior to rituximab plus CHOP (R-CHOP) in
      patients under 60 years of age, but toxicity limits its use to younger patients.
      Studies also suggest that DA-EPOCH-R (dose-adjusted etoposide, prednisone,
      vincristine, cyclophosphamide, doxorubicin, rituximab) is more effective in some
      subtypes of diffuse large B-cell lymphoma and a randomized comparison with R-CHOP
      is now nearing completion. The simplicity and safety of R-CHOP and the long
      history of failed contenders, however, has set a high bar for new approaches. 

PMID- 24319236
TI  - Targeting the epigenome and other new strategies in diffuse large B-cell
      lymphoma: beyond R-CHOP.
AB  - Diffuse large B-cell lymphoma, the most common lymphoma subtype, is curable in
      the majority of patients. However, one of the greatest unmet needs in lymphoma
      treatment remains novel approaches to prevent relapsed or refractory disease.
      Genomic profiling has provided important prognostic information that is being
      used in the development of novel therapeutic strategies currently in clinical
      trials. It is clear, however, that epigenetic alterations provide an additional
      series of targets that can be pharmacologically modified and offer great
      potential to improving patient outcomes. Greater understanding of this area is
      providing important new insights that are now being explored in the clinical
      setting. Demethylating agents and drugs that disrupt histone modifiers are in
      early clinical trials with promising results, and other approaches targeting
      epigenetic pathways are in active preclinical and early clinical development. 

PMID- 24319237
TI  - Treatment of infant leukemias: challenge and promise.
AB  - Leukemia in infants is rare but generates tremendous interest due to its
      aggressive clinical presentation in a uniquely vulnerable host, its poor response
      to current therapies, and its unique biology that is increasingly pointing the
      way toward novel therapeutic approaches. This review highlights the key clinical,
      pathologic, and epidemiologic features of infant leukemia, including the high
      frequency of mixed lineage leukemia (MLL) gene rearrangements. The state of the
      art with regard to current approaches to risk stratified treatment of infant
      leukemia in the major international cooperative groups is discussed. Finally,
      exciting recent discoveries elucidating the molecular biology of infant leukemia
      are reviewed and novel targeted therapeutic strategies, including FLT3 inhibition
      and modulation of aberrant epigenetic programs, are suggested. 

PMID- 24319238
TI  - Does hematopoietic stem cell transplantation benefit infants with acute leukemia?
AB  - A 6-month-old girl was diagnosed with acute lymphoblastic leukemia (ALL). She has
      completed induction therapy and is currently in first complete remission (CR1).
      You are asked by your resident if hematopoietic stem cell transplantation (HSCT)
      would benefit infants with acute leukemia. 

PMID- 24319239
TI  - Hemophagocytic lymphohistiocytosis: pathogenesis and treatment.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is not an independent disease but rather
      a life-threatening clinical syndrome that occurs in many underlying conditions
      and in all age groups. HLH is the consequence of a severe, uncontrolled
      hyperinflammatory reaction that in most cases is triggered by an infectious
      agent. Persistent stimulation of lymphocytes and histiocytes results in
      hypercytokinemia, leading to the characteristic symptoms of HLH. Genetic defects
      in familial HLH and in immunodeficiency syndromes associated with albinism affect
      the transport, processing, and function of cytotoxic granules in natural killer
      cells and cytotoxic T lymphocytes. This leads to defective killing of target
      cells and a failure to contract the immune response. The defects are increasingly
      found also in adolescents and adults. Acquired HLH occurs in autoinflammatory and
      autoimmune diseases (macrophage activation syndrome) and in patients with
      iatrogenic immunosuppression or with malignancies, but also in otherwise healthy
      persons with infections. Treatment of HLH aims at suppressing hypercytokinemia
      and eliminating the activated and infected cells. In genetic HLH, hematopoietic
      stem cell transplantation (HSCT) is needed for the correction of the immune
      defect. Treatment modalities include immunosuppressive, immunomodulatory, and
      cytostatic drugs; T-cell antibodies; and anticytokine agents. Using
      immunochemotherapy, familial HLH, which had been invariably fatal, has become a
      curable disease with more than 50% survivors. Reduced intensity conditioning for
      HSCT, which is associated with less transplantation-related mortality, will
      further improve cure rates. 

PMID- 24319240
TI  - Novel clinical trials for pediatric leukemias: lessons learned from genomic
      analyses.
AB  - Acute lymphoblastic leukemia in childhood has shown remarkable improvements in
      outcome over the past decades. This achievement was the result of better patient
      risk assessment, intensification of treatment, appropriate use of BM
      transplantation, and improved supportive therapies. Among risk factors, early
      response (originally morphologic and today minimal residual disease) has acquired
      a prominent role. The predictive value of minimal residual disease evaluation as
      a measurement of in vivo drug resistance opened new perspectives for its use in
      clinical evaluation to determine a risk-based treatment and as a potential
      surrogate end point for efficacy. More recently, detailed genomic analyses of
      childhood acute lymphoblastic leukemia have increased our knowledge in this
      disease. It is likely that this will lead to further improvement of risk
      assessment and stratification to targeted therapies. Leukemic subsets defined on
      the basis of biological mechanisms and driver mutations will be ever smaller. To
      facilitate continued progress, this new scenario will raise methodological issues
      in study design and the need for collaboration across large, well-characterized
      patient populations. 

PMID- 24319241
TI  - The use of platelet-rich plasma in the nonsurgical management of sports injuries:
      hype or hope?
AB  - Interest in platelet-rich plasma (PRP) has skyrocketed over the last decade, with
      a growing body of research contributing to both excitement and skepticism
      regarding its use. Despite mixed opinions in the medical field, interest from the
      public has fueled increased utilization of PRP for musculoskeletal conditions,
      particularly those that are difficult to treat such as chronic, degenerative
      tendinopathy and osteoarthritis. PRP's reputation as a "natural healer" and
      stories in the lay press featuring the use of PRP by professional athletes and
      celebrities has created a lucrative market for PRP even absent insurance
      reimbursement, casting further doubt regarding motivation for use by some
      practitioners. Research of PRP is clouded by the fact that PRP is a heterogeneous
      term representing a variety of different platelet preparations and there are many
      variables in technique and postprocedure rehabilitation, all of which may have
      significant effects on outcome. This article discusses definitions and
      classification of PRP, reviews rationale and evidence for use of PRP in chronic
      tendon injuries and osteoarthritis, and looks at future directions. 

PMID- 24319242
TI  - Blood manipulation: current challenges from an anti-doping perspective.
AB  - The delivery of oxygen is the limiting factor during whole-body endurance
      exercise in well-trained individuals, so manipulating the amount of hemoglobin in
      the blood results in changes in endurance exercise capacity. Athletes began using
      novel erythropoiesis-stimulating agents well before they were approved for
      medical use. Older manipulation practices, such as autologous blood transfusions
      or the administration of first-generation recombinant human erythropoietins, are
      still widely abused due to challenges in their detection. More recent performance
      enhancement maneuvers include efforts to mask doping and to induce increased
      endogenous erythropoietin expression. Confessions by athletes have revealed an
      ongoing yet extremely sophisticated modus operandi when manipulating the blood.
      In this review, weaknesses in detection methods and sample collection procedures
      are scrutinized and strategies developed to circumvent the test system discussed.

PMID- 24319243
TI  - Sickle cell trait testing and athletic participation: a solution in search of a
      problem?
AB  - Carriers of a single sickle cell gene mutation generally enjoy normal lifespans
      without serious health consequences related to their sickle cell status, but
      under extreme conditions such as severe dehydration and high-intensity physical
      activity, complications such as exertional rhabdomyolysis, splenic infarction,
      and papillary necrosis can occur. Recently, the National Collegiate Athletic
      Association (NCAA) adopted a policy that requires sickle cell solubility testing
      for all incoming student athletes. However, the American Society of Hematology
      (ASH) and other physician organizations oppose this policy. What is the basis for
      this controversy and how have new findings moved the field forward? I discuss
      herein the epidemiology, genetics, and clinical studies of sickle cell trait;
      review the implications of current policies regarding sickle cell trait screening
      and interventions for the student athlete; and examine additional areas where
      more information is needed. 

PMID- 24319244
TI  - Transfusion guidelines: when to transfuse.
AB  - Transfusion of blood and blood components has been a routine practice for more
      than half a century. The rationale supporting this practice is that replacement
      of blood loss should be beneficial for the patient. This assumption has
      constituted the underpinning of transfusion medicine for many decades. Only over
      the past 20 years, we have seen a more concerted effort to answer very basic
      questions regarding the value of transfusion therapy. An assessment of the value
      of transfusion based on well-designed and appropriately powered randomized,
      controlled trials is the first step in optimizing transfusion practices.
      Systematic reviews provide the second step by building the knowledge base
      necessary to assess the impact of transfusion practice on patient outcomes. The
      third step is the development of clinical practice guidelines, and this occurs
      when systematic reviews are interpreted by individuals with expertise in
      transfusion medicine. Such guidelines are typically supported by professional
      organizations and/or health authorities. Implementation of clinical practice
      guidelines can be challenging, especially in an area as heterogeneous as
      transfusion medicine. However, clinical practice guidelines are necessary for the
      practice of evidence-based medicine, which optimizes patient care and improves
      patient outcomes. This review focuses on clinical practice guidelines for
      transfusion of three blood components: RBCs, platelets and plasma. In addition,
      we provide the approach used to implement clinical practice guidelines at our own
      institution. 

PMID- 24319245
TI  - Hemochromatosis: the new blood donor.
AB  - Hereditary hemochromatosis (HH) due to homozygosity for the C282Y mutation in the
      HFE gene is a common inherited iron overload disorder in whites of northern
      European descent. Hepcidin deficiency, the hallmark of the disorder, leads to
      dysregulated intestinal iron absorption and progressive iron deposition in the
      liver, heart, skin, endocrine glands, and joints. Survival is normal if organ
      damage is prevented by early institution of phlebotomy therapy. HH arthropathy is
      the symptom most affecting quality of life and can be debilitating. Genotype
      screening in large population studies has shown that the clinical penetrance of
      C282Y homozygosity is highly variable and can be very low, with up to 50% of
      women and 20% of men showing a silent phenotype. Targeted population screening
      for the HFE C282Y mutation is not recommended at present, but might be
      reconsidered as a cost-effective approach to management if counseling and care
      were better organized and standardized. Referral of patients to the blood center
      for phlebotomy therapy and use of HH donor blood for transfusion standardizes
      treatment, minimizes treatment costs, and may benefit society as a whole.
      Physician practices should be amended such that HH subjects are more frequently
      referred to the blood center for therapy. 

PMID- 24319246
TI  - Fresh versus old blood: are there differences and do they matter?
AB  - The medical effects of transfusing stored RBCs is an area of significant concern
      that has received substantial attention in recent years. Retrospective trials
      show all possible outcomes, including sequelae from transfusing older RBCs, no
      difference between older and fresher RBCs, and a benefit to older RBCs. Several
      prospective clinical trials are under way to further investigate potential
      untoward effects of stored RBCs. Thus far, the issue of potential sequelae from
      transfusing stored RBCs remains a highly controversial issue. However, what is
      not controversial is that RBC storage is an unnatural state during which a series
      of substantial changes take place to the stored RBCs. These changes result in the
      formation of cellular and chemical entities known to have biological activities
      in other settings, giving rise to several distinct hypotheses by which stored
      RBCs may alter recipient biology. Herein, the clinical background and basic
      science of RBC storage are reviewed, with a particular focus on factors that may
      complicate hypothesis testing and obfuscate underlying biologies. The complexity
      of the RBC storage lesion, donor-to-donor variation, and the diversity of
      recipient pathophysiologies remain a challenge to prospective trials assessing
      the safety of stored RBCs. 

PMID- 24319247
TI  - Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the
      surgeon's perspective.
AB  - Over the past century, blood banking and transfusion practices have moved from
      whole blood therapy to components. In trauma patients, the shift to component
      therapy was achieved without clinically validating which patients needed which
      blood products. Over the past 4 decades, this lack of clinical validation has led
      to uncertainty on how to optimally use blood products and has likely resulted in
      both overuse and underuse in injured patients. However, recent data from both US
      military operations and civilian trauma centers have shown a survival advantage
      with a balanced transfusion ratio of RBCs, plasma, and platelets. This has been
      extended to include the prehospital arena, where thawed plasma, RBCs, and
      antifibrinolytics are becoming more widely used. The Texas Trauma Institute in
      Houston has followed this progression by putting RBCs and thawed plasma in the
      emergency department and liquid plasma and RBCs on helicopters, transfusing
      platelets earlier, and using thromboelastogram-guided approaches. These changes
      have not only resulted in improved outcomes, but have also decreased inflammatory
      complications, operations, and overall use of blood products. In addition,
      studies have shown that resuscitating with plasma (instead of crystalloid)
      repairs the "endotheliopathy of trauma," or the systemic endothelial injury and
      dysfunction that lead to coagulation disturbances and inflammation. Data from the
      Trauma Outcomes Group, the Prospective Observational Multicenter Major Trauma
      Transfusion (PROMMTT) study, and the ongoing Pragmatic Randomized Optimal
      Platelet and Plasma Ratios (PROPPR) trial represent a decade-long effort to
      programmatically determine optimal resuscitation practices, balancing risk versus
      benefits. With injury as the leading cause of death in patients age 1 to 44 years
      and hemorrhage the leading cause of potentially preventable death in this group,
      high-quality data must be obtained to provide superior care to the civilian and
      combat injured. 

PMID- 24319248
TI  - Mechanisms of trauma-induced coagulopathy.
AB  - The identification and management of coagulopathy is a critical component of
      caring for the severely injured patient. Notions of the mechanisms of
      coagulopathy in trauma patients have been supplanted by new insights resulting
      from close examination of the biochemical and cellular changes associated with
      acute tissue injury and hemorrhagic shock. Acute intrinsic coagulopathy arising
      in severely injured trauma patients is now termed trauma-induced coagulopathy
      (TIC) and is an emergent property of tissue injury combined with hypoperfusion.
      Mechanisms contributing to TIC include anticoagulation, consumption, platelet
      dysfunction, and hyperfibrinolysis. This review discusses current understanding
      of TIC mechanisms and their relative contributions to coagulopathy in the face of
      increasingly severe injury and highlights how they interact to produce
      coagulation system dysfunction. 

PMID- 24319249
TI  - Resuscitation of trauma-induced coagulopathy.
AB  - For 30 years, the Advanced Trauma Life Support course of the American College of
      Surgeons taught that coagulopathy was a late consequence of resuscitation of
      injury. The recognition of trauma-induced coagulopathy overturns that medical
      myth and creates a rationale for procoagulant resuscitation. Analysis of the
      composition of currently available blood components allows prediction of the
      upper limits of achievable coagulation activity, keeping in mind that oxygen
      transport must be maintained simultaneously. RBCs, plasma, and platelets given in
      a 1:1:1 unit ratio results in a hematocrit of 29%, plasma concentration of 62%,
      and platelet count of 90,000 in the administered resuscitation fluid. Additional
      amounts of any 1 component dilute the other 2 and any other fluids given dilute
      all 3. In vivo recovery of stored RBCs is ~90% and that of platelets ~60% at the
      mean age at which such products are given to trauma patients. This means that
      useful concentrations of the administered products are a hematocrit of 26%, a
      plasma coagulation factor activity of 62% equivalent to an international
      normalized ratio of ~1.2, and a platelet count of 54,000. This means there is
      essentially no good way to give blood products for resuscitation of trauma
      induced coagulopathy other than 1:1:1. Because 50% of trauma patients admitted
      alive to an academic-level 1 trauma center who will die of uncontrolled
      hemorrhage will be dead in 2 hours, the trauma system must be prepared to deliver
      plasma- and platelet-based resuscitation at all times.

PMID- 24319251
TI  - Antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is defined by venous or arterial thrombosis
      and/or pregnancy morbidity in patients with persistent presence of
      antiphospholipid antibodies (aPLs). Catastrophic APS is the most severe form of
      APS, which is associated with rapid development of microvascular thrombosis
      resulting in multiorgan failure in patients with aPLs. Patients with APS and
      catastrophic APS are recognized to have a high risk of recurrent thrombosis that
      can occur despite anticoagulant therapy. Although antithrombotic therapy remains
      the mainstay of treatment, bleeding manifestations can complicate management and
      contribute to increased morbidity. Patients with persistently elevated aPL
      levels, particularly those who exhibit positive testing for lupus anticoagulant,
      anticardiolipin antibodies, and anti-beta2GPI antibodies (triple positivity),
      appear to be at increased risk for thrombosis and pregnancy complications,
      whereas isolated positivity for aPLs appears to be associated with low risk.
      Recognizing that patients with APS have different thrombotic risk profiles may
      assist clinicians in assessing the risks and benefits of anticoagulation. The
      optimal type, intensity, and duration of anticoagulation in the treatment of APS
      remain controversial, particularly for arterial thrombosis and recurrent
      thrombosis. Future studies that delineate thrombotic risk in APS and evaluate
      current and novel anticoagulants as well as nonanticoagulant therapies are
      required. 

PMID- 24319250
TI  - Heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by
      antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. HIT
      is frequently considered in the differential diagnosis of thrombocytopenia
      occurring in patients on heparin therapy. HIT is a challenging diagnosis because
      of routine heparin use in hospitalized patients, the common occurrence of
      thrombocytopenia, and high rates of anti-PF4/heparin seroconversions in patients
      treated with heparin. Our diagnostic approach to HIT is presented here,
      underscoring critical elements of clinical and laboratory evaluation. 

PMID- 24319252
TI  - Should the presence of an antiphospholipid antibody affect the duration of
      anticoagulant treatment in patients with venous thromboembolism?
AB  - A 44-year-old otherwise healthy woman has completed 3 months of anticoagulation
      therapy for a first episode of unprovoked pulmonary embolism. At the time of
      diagnosis and before the initiation of anticoagulation, she was found to have an
      elevated IgG anticardiolipin antibody (ACLA), which was measured at 42 IgG
      phospholipid (GPL) units (reference range, <15 GPL units) with negative lupus
      anticoagulant (LAC) testing. Should this laboratory finding affect the
      recommended duration of anticoagulant therapy?

PMID- 24319253
TI  - Cancer-associated thrombosis.
AB  - Cancer-associated thrombosis accounts for almost one-fifth of all cases of venous
      thromboembolism (VTE) and is a leading cause of death, morbidity, delays in care,
      and increased costs. Our understanding of risk factors for cancer-associated
      thrombosis has expanded in recent years, and investigators have begun to use
      biomarkers and clinical prediction models to identify those cancer patients at
      greatest risk for VTE. The Khorana Risk Model, which is based on easily obtained
      biomarkers and clinical factors, has now been validated in several studies.
      Recent clinical trials of prophylaxis and treatment of VTE in cancer patients are
      reviewed here. In addition, consensus guidelines and expert opinion regarding
      management of VTE in specific challenging situations are presented. 

PMID- 24319254
TI  - A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5
      induces apoptosis in multiple myeloma and overcomes bortezomib resistance.
AB  - Proteasome inhibitors have demonstrated that targeting protein degradation is
      effective therapy in multiple myeloma (MM). Here we show that deubiquitylating
      enzymes (DUBs) USP14 and UCHL5 are more highly expressed in MM cells than in
      normal plasma cells. USP14 and UCHL5 short interfering RNA knockdown decreases MM
      cell viability. A novel 19S regulatory particle inhibitor b-AP15 selectively
      blocks deubiquitylating activity of USP14 and UCHL5 without inhibiting proteasome
      activity. b-AP15 decreases viability in MM cell lines and patient MM cells,
      inhibits proliferation of MM cells even in the presence of bone marrow stroma
      cells, and overcomes bortezomib resistance. Anti-MM activity of b-AP15 is
      associated with growth arrest via downregulation of CDC25C, CDC2, and cyclin B1
      as well as induction of caspase-dependent apoptosis and activation of unfolded
      protein response. In vivo studies using distinct human MM xenograft models show
      that b-AP15 is well tolerated, inhibits tumor growth, and prolongs survival.
      Combining b-AP15 with suberoylanilide hydroxamic acid, lenalidomide, or
      dexamethasone induces synergistic anti-MM activity. Our preclinical data showing
      efficacy of b-AP15 in MM disease models validates targeting DUBs in the ubiquitin
      proteasomal cascade to overcome proteasome inhibitor resistance and provides the
      framework for clinical evaluation of USP14/UCHL5 inhibitors to improve patient
      outcome in MM. 

PMID- 24319257
TI  - Reduction in lung cancer deaths is lagging behind that in other common cancers.

PMID- 24319255
TI  - The CCAAT box-binding transcription factor NF-YA1 controls rhizobial infection.
AB  - Symbiosis between legume plants and soil rhizobia culminates in the formation of
      a novel root organ, the 'nodule', containing bacteria differentiated as
      facultative nitrogen-fixing organelles. MtNF-YA1 is a Medicago truncatula CCAAT
      box-binding transcription factor (TF), formerly called HAP2-1, highly expressed
      in mature nodules and required for nodule meristem function and persistence. Here
      a role for MtNF-YA1 during early nodule development is demonstrated. Detailed
      expression analysis based on RNA sequencing, quantitiative real-time PCR (qRT
      PCR), as well as promoter-beta-glucuronidase (GUS) fusions reveal that MtNF-YA1
      is first induced at the onset of symbiotic development during preparation for,
      and initiation and progression of, symbiotic infection. Moreover, using a new
      knock-out mutant, Mtnf-ya1-1, it is shown that MtNF-YA1 controls infection thread
      (IT) progression from initial root infection through colonization of nodule
      tissues. Extensive confocal and electronic microscopic observations suggest that
      the bulbous and erratic IT growth phenotypes observed in Mtnf-ya1-1 could be a
      consequence of the fact that walls of ITs in this mutant are thinner and less
      coherent than in the wild type. It is proposed that MtNF-YA1 controls rhizobial
      infection progression by regulating the formation and the wall of ITs. 

PMID- 24319256
TI  - Structural-functional dissection and characterization of yield-contributing
      traits originating from a group 7 chromosome of the wheatgrass species Thinopyrum
      ponticum after transfer into durum wheat.
AB  - For the first time, using chromosome engineering of durum wheat, the underlying
      genetic determinants of a yield-improving segment from Thinopyrum ponticum (7AgL)
      were dissected. Three durum wheat-Th. ponticum near-isogenic recombinant lines
      (NIRLs), with distal portions of their 7AL arm (fractional lengths 0.77, 0.72,
      and 0.60) replaced by alien chromatin, were field-tested for two seasons under
      rainfed conditions. Yield traits and other agronomic characteristics of the main
      shoot and whole plant were measured. Loci for seed number per ear and per
      spikelet were detected in the proximal 7AgL segment (0.60-0.72). Loci determining
      considerable increases of flag leaf width and area, productive tiller number per
      plant, biomass per plant, and grain yield per plant were located in the distally
      adjacent 0.72-0.77 7AgL segment, while in the most distal portion (0.77-1.00)
      genetic effects on spikelet number per ear were identified. Contrary to previous
      reports, trials with the bread wheat T4 translocation line, carrying on 7DL a
      sizeable 7AgL segment of which those present in the durum wheat-Th. ponticum
      NIRLs represent fractions, gave no yield advantage. The hypothesis that ABA might
      be a factor contributing to the 7AgL effects was tested by analysing endogenous
      ABA contents of the NIRLs and their responses to exogenous ABA application. The
      7AgL yield-related loci were shown to be ABA-independent. This study highlights
      the value of wheat-alien recombinant lines for dissecting the genetic and
      physiological basis of complex traits present in wild germplasm, and provides a
      basis for their targeted exploitation in wheat breeding. 

PMID- 24319258
TI  - Prognosis of respiratory tract infections in primary care.

PMID- 24319260
TI  - Court approved caesarean section for mentally ill woman because of two previous
      caesareans.

PMID- 24319259
TI  - Pfizer's open data policy should include trials of off-label uses, say critics.

PMID- 24319261
TI  - Europe drug regulator wins appeal over release of trial data.

PMID- 24319263
TI  - Anti-HIV antibody-dependent activation of NK cells impairs NKp46 expression.
AB  - There is much interest in the potential of Ab-dependent cellular cytotoxicity
      (ADCC) to slow disease progression following HIV infection. Despite several
      studies demonstrating a positive association between ADCC and slower disease
      progression, it is possible that continued stimulation of NK cells by ADCC during
      chronic HIV infection could render these cells dysfunctional. Indeed, activation
      of NK cells by ADCC results in matrix metalloproteinase-induced reductions in
      CD16 expression and activation refractory periods. In addition, ex vivo analyses
      of NK cells from HIV-infected individuals revealed other alterations in
      phenotype, such as decreased expression of the activating NKp46 receptor that is
      essential for NK-mediated antitumor responses and immunity from infection.
      Because NKp46 shares a signaling pathway with CD16, we hypothesized that
      activation-induced downregulation of both receptors could be controlled by a
      common mechanism. We found that activation of NK cells by anti-HIV or anti-CD16
      Abs resulted in NKp46 downregulation. The addition of a matrix metalloproteinase
      inhibitor attenuated NKp46 downregulation following NK cell activation by anti
      HIV Abs. Consequently, these results suggest that continued stimulation through
      CD16 has the potential to impair natural cytotoxicity via attenuation of NKp46
      dependent signals. 

PMID- 24319264
TI  - "Activated" STAT proteins: a paradoxical consequence of inhibited JAK-STAT
      signaling in cytomegalovirus-infected cells.
AB  - We have previously characterized mouse CMV (MCMV)-encoded immune-evasive IFN
      signaling inhibition and identified the viral protein pM27 as inducer of
      proteasomal degradation of STAT2. Extending our analysis to STAT1 and STAT3, we
      found that MCMV infection neither destabilizes STAT1 protein nor prevents STAT1
      tyrosine Y701 phosphorylation, nuclear translocation, or the capability to bind
      gamma-activated sequence DNA-enhancer elements. Unexpectedly, the analysis of
      STAT3 revealed an induction of STAT3 Y705 phosphorylation by MCMV. In parallel,
      we found decreasing STAT3 protein amounts upon MCMV infection, although STAT3
      expression normally is positive autoregulative. STAT3 phosphorylation depended on
      the duration of MCMV infection, the infectious dose, and MCMV gene expression but
      was independent of IFNAR1, IL-10, IL-6, and JAK2. Although STAT3 phosphorylation
      did not require MCMV immediate early 1, pM27, and late gene expression, it was
      restricted to MCMV-infected cells and not transmitted to bystander cells. Despite
      intact STAT1 Y701 phosphorylation, IFN-gamma-induced target gene transcription
      (e.g., IRF1 and suppressor of cytokine signaling [SOCS] 1) was strongly impaired.
      Likewise, the induction of STAT3 target genes (e.g., SOCS3) by IL-6 was also
      abolished, indicating that MCMV antagonizes STAT1 and STAT3 despite the
      occurrence of tyrosine phosphorylation. Consistent with the lack of SOCS1
      induction, STAT1 phosphorylation was prolonged upon IFN-gamma treatment. We
      conclude that the inhibition of canonical STAT1 and STAT3 target gene expression
      abrogates their intrinsic negative feedback loops, leading to accumulation of
      phospho-tyrosine-STAT3 and prolonged STAT1 phosphorylation. These findings
      challenge the generalization of tyrosine-phosphorylated STATs necessarily being
      transcriptional active and document antagonistic effects of MCMV on STAT1/3
      dependent target gene expression. 

PMID- 24319262
TI  - The p53 transcription factor modulates microglia behavior through microRNA
      dependent regulation of c-Maf.
AB  - Neuroinflammation occurs in acute and chronic CNS injury, including stroke,
      traumatic brain injury, and neurodegenerative diseases. Microglia are specialized
      resident myeloid cells that mediate CNS innate immune responses. Disease-relevant
      stimuli, such as reactive oxygen species (ROS), can influence microglia
      activation. Previously, we observed that p53, a ROS-responsive transcription
      factor, modulates microglia behaviors in vitro and in vivo, promoting
      proinflammatory functions and suppressing downregulation of the inflammatory
      response and tissue repair. In this article we describe a novel mechanism by
      which p53 modulates the functional differentiation of microglia both in vitro and
      in vivo. Adult microglia from p53-deficient mice have increased expression of the
      anti-inflammatory transcription factor c-Maf. To determine how p53 negatively
      regulates c-Maf, we examined the impact of p53 on known c-Maf regulators. MiR-155
      is a microRNA that targets c-Maf. We observed that cytokine-induced expression of
      miR-155 was suppressed in p53-deficient microglia. Furthermore, Twist2, a
      transcriptional activator of c-Maf, is increased in p53-deficient microglia. We
      identified recognition sites in the 3' untranslated region of Twist2 mRNA that
      are predicted to interact with two p53-dependent microRNAs: miR-34a and miR-145.
      In this article, we demonstrate that miR-34a and -145 are regulated by p53 and
      negatively regulate Twist2 and c-Maf expression in microglia and the RAW
      macrophage cell line. Taken together, these findings support the hypothesis that
      p53 activation induced by local ROS or accumulated DNA damage influences
      microglia functions and that one specific molecular target of p53 in microglia is
      c-Maf. 

PMID- 24319265
TI  - Immunization with a recombinant bacillus Calmette-Guerin strain confers
      protective Th1 immunity against the human metapneumovirus.
AB  - Along with the human respiratory syncytial virus (hRSV), the human
      metapneumovirus (hMPV) is one of the leading causes of childhood hospitalization
      and a major health burden worldwide. Unfortunately, owing to an inefficient
      immunological memory, hMPV infection provides limited immune protection against
      reinfection. Furthermore, hMPV can induce an inadequate Th2 type immune response
      that causes severe lung inflammation, leading to airway obstruction. Similar to
      hRSV, it is likely that an effective clearance of hMPV would require a balanced
      Th1 type immunity by the host, involving the activation of IFN-gamma-secreting T
      cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus
      Calmette-Guerin (BCG), which has been used in newborns for many decades and in
      several countries as a tuberculosis vaccine. We have previously shown that
      immunization with BCG strains expressing hRSV Ags can induce an efficient immune
      response that protects against this virus. In this study, we show that
      immunization with rBCG strains expressing the phosphoprotein from hMPV also can
      induce protective Th1 immunity. Mice immunized with rBCG were protected against
      weight loss, airway inflammation, and viral replication in the lungs after hMPV
      infection. Our rBCG vaccine also induced the activation of hMPV-specific T cells
      producing IFN-gamma and IL-2, which could protect from hMPV infection when
      transferred to recipient mice. These data strongly support the notion that rBCG
      induces protective Th1 immunity and could be considered as an efficient vaccine
      against hMPV. 

PMID- 24319268
TI  - Study busts myth of "metabolically healthy" obesity.

PMID- 24319269
TI  - Judge allows boy to have bone marrow transplant against father's wishes.

PMID- 24319266
TI  - The pore-forming toxin listeriolysin O is degraded by neutrophil
      metalloproteinase-8 and fails to mediate Listeria monocytogenes intracellular
      survival in neutrophils.
AB  - The pore-forming toxin listeriolysin O (LLO) is a major virulence factor secreted
      by the facultative intracellular pathogen Listeria monocytogenes. This toxin
      facilitates L. monocytogenes intracellular survival in macrophages and diverse
      nonphagocytic cells by disrupting the internalization vesicle, releasing the
      bacterium into its replicative niche, the cytosol. Neutrophils are innate immune
      cells that play an important role in the control of infections, yet it was
      unknown if LLO could confer a survival advantage to L. monocytogenes in
      neutrophils. We report that LLO can enhance the phagocytic efficiency of human
      neutrophils and is unable to protect L. monocytogenes from intracellular killing.
      To explain the absence of L. monocytogenes survival in neutrophils, we
      hypothesized that neutrophil degranulation leads to the release of LLO
      neutralizing molecules in the forming phagosome. In support of this, L.
      monocytogenes is a potent inducer of neutrophil degranulation, since its
      virulence factors, such as LLO, facilitate granule exocytosis. Within the first
      few minutes of interaction with L. monocytogenes, granules can fuse with the
      plasma membrane at the bacterial interaction site before closure of the
      phagosome. Furthermore, granule products directly degrade LLO, irreversibly
      inhibiting its activity. The matrix metalloproteinase-8, stored in secondary
      granules, was identified as an endoprotease that degrades LLO, and blocking
      neutrophil proteases increased L. monocytogenes intracellular survival. In
      conclusion, we propose that LLO degradation by matrix metalloproteinase-8 during
      phagocytosis protects neutrophil membranes from perforation and contributes to
      maintaining L. monocytogenes in a bactericidal phagosome from which it cannot
      escape. 

PMID- 24319270
TI  - States choosing not to expand Medicaid stand to lose billions, study concludes.

PMID- 24319267
TI  - Soluble gC1qR is an autocrine signal that induces B1R expression on endothelial
      cells.
AB  - Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs
      to the kinin family of proinflammatory peptides. BK induces its activity via two
      G protein-coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK
      receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced
      by IL-1beta. The C1q receptor, receptor for the globular heads of C1q (gC1qR),
      which plays a role in BK generation, is expressed on activated ECs and is also
      secreted as soluble gC1qR (sgC1qR). Because sgC1qR can bind to ECs, we
      hypothesized that it may also serve as an autocrine/paracrine signal for the
      induction of B1R expression. In this study, we show that gC1qR binds to ECs via a
      highly conserved domain consisting of residues 174-180, as assessed by solid
      phase binding assay and deconvolution fluorescence microscopy. Incubation of ECs
      (24 h, 37  degrees C) with sgC1qR resulted in enhancement of B1R expression,
      whereas incubation with gC1qR lacking aa 174-180 and 154-162 had a diminished
      effect. Binding of sgC1qR to ECs was through surface-bound fibrinogen and was
      inhibited by anti-fibrinogen. In summary, our data suggest that, at sites of
      inflammation, sgC1qR can enhance vascular permeability by upregulation of B1R
      expression through de novo synthesis, as well as rapid translocation of preformed
      B1R.

PMID- 24319271
TI  - Lack of knowledge of physical activity guidelines: can physical activity
      promotion campaigns do better?
AB  - OBJECTIVES: To identify the prevalence of knowledge of the current UK physical
      activity guidelines which were introduced in 2011 and prior physical activity
      guidelines (30 min on 5 days each week) within two large samples of UK adult's.
      To investigate whether knowledge of physical activity guidelines differs
      according to demographics such as ethnicity, age, education and employment
      status. DESIGN: Descriptive cross-sectional study comparing two distinctive adult
      samples. SETTING: National survey and online-administered survey conducted in
      England. PARTICIPANTS: The 2007 Health Survey for England provides data on
      knowledge of physical activity guidelines from 2860 UK adults (56% women, 89%
      white, 63% under 45 years old). In 2013, an online survey was disseminated and
      data were collected from 1797 UK adults on knowledge of the most recent physical
      activity guidelines. The 2013 sample was 70% women, 92% white and 57% under 45
      years old. All adults in both samples were >18 years old and without
      illnesses/disorders likely to restrict physical activity. MAIN OUTCOMES:
      Knowledge of physical activity guidelines in 2007 and 2013. Demographic
      correlates of knowledge of moderate-to-vigorous physical activity guidelines.
      RESULTS: 18% of the 2013 sample accurately recalled the current physical activity
      guidelines compared with 11% of the 2007 sample who accurately recalled the
      previous guidelines. The differences in knowledge of physical activity guidelines
      existed for marital status, gender, age, education and employment status within
      both 2007 and 2013 samples (p<0.05). Men with lower education and employment
      status (unemployed including student and retired) and older adults were less
      likely to know physical activity guidelines (p<0.05). Knowledge of physical
      activity guidelines remained higher in the 2013 sample after controlling for
      demographic differences (p<0.05). CONCLUSIONS: Disadvantaged population groups
      are less knowledgeable about physical activity guidelines. Although knowledge of
      physical activity guidelines appears to have increased in recent years
      demographic disparities are still evident. Efforts are needed to promote health
      information among these groups.

PMID- 24319272
TI  - Rounding of birth weights in a neonatal intensive care unit over 20 years: an
      analysis of a large cohort study.
AB  - OBJECTIVE: To determine the frequency of birth weight digit preference for
      infants admitted to a large neonatal intensive care unit (NICU), the scale of
      rounding and its dependence on birth weight, and time and the impact on
      prescribing accuracy. DESIGN: A consecutive cohort of birth weights extracted
      retrospectively from a single clinical database. SETTING AND PARTICIPANTS: Birth
      weights from 9170 inborn infants recorded on an electronic prescribing database
      admitted to NICU over 20 years. STATISTICAL APPROACH: Data are presented for the
      frequency of each of the possible pairs of final digits. A statistical model of
      digit preference assuming rounding is used to quantify the proportions rounding
      to specific accuracy levels. These proportions are compared between those <1000 g
      and those above and over the 20-year time period. RESULTS: From a population of
      9170 infants admitted over 20 years, there was a highly statistically significant
      digit bias with an increased prevalence of multiples of 100 (p<0.0001), 50
      (p=0.007), 20 (p<0.0001), 10 (p<0.0001), 5 (p<0.0001) and 2 (p=0.0005). There was
      clear evidence of a reduced 100 g digit bias for infants 500 and 1000 g (0%)
      compared with those between 1000 and 4500 g (3.7%). The maximum birth weight
      error due to digit bias for all infants was 5%. There was clear evidence of an
      improvement in accuracy over 20 years. CONCLUSIONS: Digit bias in birth weights
      over 20 years in a tertiary NICU is highly significant at the 100, 50, 20, 10, 5
      and 2-digit levels. There has been a substantial improvement in the accuracy of
      birth weight measurements over 20 years. The likely maximum error due to birth
      weight digit bias is 5% and is within an acceptable tolerance for drug dosing
      even at very low birth weights.

PMID- 24319273
TI  - A case-control study of incident rheumatological conditions following acute
      gastroenteritis during military deployment.
AB  - OBJECTIVES: The aim of this study was to assess the risk of incident
      rheumatological diagnoses (RD) associated with self-reported diarrhoea and
      vomiting during a first-time deployment to Iraq or Afghanistan. Such an
      association would provide evidence that RD in this population may include
      individuals with reactive arthritis (ReA) from deployment-related infectious
      gastroenteritis. DESIGN: This case-control epidemiological study used univariate
      and multivariate logistic regression to compare the odds of self-reported
      diarrhoea/vomiting among deployed US military personnel with incident RD to the
      odds of diarrhoea/vomiting among a control population. SETTING: We analysed
      health records of personnel deployed to Iraq or Afghanistan, including responses
      on a postdeployment health assessment and medical follow-up postdeployment.
      PARTICIPANTS: Anonymous data were obtained from 891 US military personnel with at
      least 6 months of medical follow-up following a first-time deployment to Iraq or
      Afghanistan in 2008-2009. Cases were defined using International Classification
      of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes;
      controls had an unrelated medical encounter and were representative of the study
      population. MAIN OUTCOME MEASURES: The primary measure was an association between
      incident RD and self-reported diarrhoea/vomiting during deployment. A secondary
      measure was the overall incidence of RD in this population. RESULTS: We
      identified 98 cases of new onset RD, with a total incidence of 161/100 000
      persons. Of those, two participants had been diagnosed with Reiter's disease (i)
      (3.3/100 000 persons) and the remainder with non-specific arthritis/arthralgia
      (157.5/100 000 persons). The OR for acute diarrhoea was 2.67 (p=0.03) after
      adjusting for important covariates. CONCLUSIONS: Incident rheumatological
      conditions, even those classified as 'non-specific,' are significantly associated
      with prior severe diarrhoea in previously deployed military personnel,
      potentially indicating ReA and need for preventive measures to reduce
      diarrhoeagenic bacterial exposures in military personnel and other travellers to
      the developing regions.

PMID- 24319274
TI  - The complexity of managing COPD exacerbations: a grounded theory study of
      European general practice.
AB  - OBJECTIVES: To understand the concerns and challenges faced by general
      practitioners (GPs) and respiratory physicians about primary care management of
      acute exacerbations in patients with chronic obstructive pulmonary disease
      (COPD). DESIGN: 21 focus group discussions (FGDs) were performed in seven
      countries with a Grounded Theory approach. Each country performed three rounds of
      FGDs. SETTING: Primary and secondary care in Norway, Germany, Wales, Poland,
      Russia, The Netherlands, China (Hong Kong). PARTICIPANTS: 142 GPs and respiratory
      physicians were chosen to include urban and rural GPs as well as hospital-based
      and out patient-clinic respiratory physicians. RESULTS: Management of acute COPD
      exacerbations is dealt with within a scope of concerns. These concerns range from
      'dealing with comorbidity' through 'having difficult patients' to 'confronting a
      hopeless disease'. The first concern displays medical uncertainty regarding
      diagnosis, medication and hospitalisation. These clinical processes become
      blurred by comorbidity and the social context of the patient. The second concern
      shows how patients receive the label 'difficult' exactly because they need
      complex attention, but even more because they are time consuming, do not take
      responsibility and are non-compliant. The third concern relates to the emotional
      reactions by the physicians when confronted with 'a hopeless disease' due to the
      fact that most of the patients do not improve and the treatment slows down the
      process at best. GPs and respiratory physicians balance these concerns with
      medical knowledge and practical, situational knowledge, trying to encompass the
      complexity of a medical condition. CONCLUSIONS: Knowing the patient is essential
      when dealing with comorbidities as well as with difficult relations in the
      consultations on exacerbations. This study suggests that it is crucial to improve
      the collaboration between primary and secondary care, in terms of, for example,
      shared consultations and defined work tasks, which may enhance shared knowledge
      of patients, medical decision-making and improved management planning.

PMID- 24319275
TI  - Associations of HIV infection with insulin and glucose levels in antiretroviral
      naive Rwandan women: a cross-sectional analysis.
AB  - OBJECTIVES: The purpose of these analyses was to determine the associations of
      HIV infection and related immune dysfunction with a glucose homeostasis in the
      population of antiretroviral-naive HIV-infected and uninfected Rwandan women. We
      hypothesise that insulin resistance and its consequences in the developing
      countries may be further elevated with HIV infection itself regardless of
      antiretroviral therapy. STUDY DESIGN: Cross-sectional analysis of a longitudinal
      cohort. SETTING: Community-based women's associations. PARTICIPANTS: In 2005, 710
      HIV-infected (HIV positive) antiretroviral naive and 226 HIV-uninfected (HIV
      negative) women were enrolled in the Rwanda Women's Interassociation Study and
      Assessment (RWISA). Clinical and demographic parameters, CD4 count, fasting
      insulin and glucose levels, anthropometric measurements and Bioelectrical
      Impedance Analysis (BIA) were obtained. Linear models were fit to log-transformed
      Homeostasis Model Assessment (HOMA) with results exponentiated back to a
      multiplicative effect on the original scale. PRIMARY OUTCOME MEASURES: The
      outcome, insulin resistance, was measured by the HOMA, calculated as fasting
      insulin (MUU/mL)*fasting glucose (mmol/L)/22.5. RESULTS: In adjusted models, HIV
      positive women were less insulin resistant than HIV-negative; an HIV-positive
      woman tended to have 0.728 times as much (95% CI 0.681 to 0.861) HOMA than a
      comparable HIV-negative woman. Among the HIV-positive women, those with CD4 <200
      cells/uL tended to have 0.741 times as much HOMA (95% CI 0.601 to 0.912) as did
      comparable women with CD4 >350 cells/uL. The older age was independently
      associated with a lower HOMA insulin resistance. After adjusting for body mass
      index, fat and fat-free mass were not independently associated with HOMA.
      CONCLUSIONS: This study found that HIV infection and more advanced HIV infection
      (CD4 counts <200 cells/uL) were associated with greater insulin sensitivity in
      antiretroviral naive African women. These findings provide baseline information
      for the interpretation of future studies on the effect of antiretroviral therapy
      on metabolic insulin sensitivity derangements in African population.

PMID- 24319276
TI  - Ozone air pollution and ischaemic stroke occurrence: a case-crossover study in
      Nice, France.
AB  - OBJECTIVES: Relationship between low-level air pollution and stroke is
      conflicting. This study was conducted to document the relationship between
      outdoor air pollution and ischaemic stroke occurrence. DESIGN: Time-stratified
      case-crossover analysis. SETTING: University Hospital of Nice, France.
      PARTICIPANTS: All consecutive patients with ischaemic stroke living in Nice
      admitted in the University Hospital of Nice (France) between January 2007 and
      December 2011. MAIN OUTCOME MEASURE: Association (adjusted OR) between daily
      levels of outdoor pollutants (ozone (O3), nitrogen dioxide (NO2), particulate
      matter (PM10) and sulfur dioxide (SO2)) and ischaemic stroke occurrence. RESULTS:
      1729 patients with ischaemic stroke (mean age: 76.1+/-14.0 years; men: 46.7%)
      were enrolled. No significant association was found between stroke occurrence and
      short-term effects of all pollutants tested. In stratified analysis, we observed
      significant associations only between recurrent (n=280) and large artery
      ischaemic stroke (n=578) onset and short-term effect of O3 exposure. For an
      increase of 10 ug/m(3) of O3 level, recurrent stroke risk (mean D-1, D-2 and D-3
      lag) was increased by 12.1% (95% CI 1.5% to 23.9%) and large artery stroke risk
      (mean D-3 and D-4 lag) was increased by 8% (95% CI 2.0% to 16.6%). Linear dose
      response relationship for both subgroups was found. CONCLUSIONS: Our results
      confirm the relationship between low-level O3 exposure and ischaemic stroke in
      high vascular risk subgroup with linear exposure-response relation, independently
      of other pollutants and meteorological parameters. The physiopathological
      processes underlying this association between ischaemic stroke and O3 exposure
      remain to be investigated.

PMID- 24319277
TI  - Association between limiting longstanding illness in mothers and their children:
      findings from the UK Millennium Cohort Study.
AB  - OBJECTIVE: To explore the association between maternal disability as measured by
      the presence of a limiting longstanding illness (LLI) 9 months postpartum and
      subsequent child health at the age of 7 years. DESIGN: Nationally representative
      prospective longitudinal study. SETTING: England, Scotland, Wales and Northern
      Ireland. PARTICIPANTS: Secondary analysis of data on 11 807 mother-child pairs
      recruited to the UK Millennium Cohort Study. Baseline interviews with mothers
      were carried out in 2001-2002. When the children were 7 years old, the follow-up
      survey included questions about limiting longstanding health conditions in the
      child. PRIMARY OUTCOME MEASURE: Any longstanding condition that was reported to
      limit the children's activities in any way. RESULTS: Nearly 7% of all children
      were reported to have an LLI at the age of 7 years. The majority (88.1%, 95% CI
      85.6% to 90.2%) of children whose mother was disabled did not have an LLI
      themselves. The children of disabled mothers, however, had higher odds of LLI
      (OR=1.9, 95% CI 1.5 to 2.5) independently of different maternal, pregnancy and
      birth characteristics and breast feeding duration. Inclusion of poverty measures
      in the model did not significantly affect the odds (OR=1.8, 95% CI 1.4 to 2.4),
      suggesting that maternal LLI around the time of birth increases the odds of child
      LLI at the age of 7 years independently of starting life in poverty. CONCLUSIONS:
      There is a strong positive association between maternal and child LLI. Health
      professionals should work together with social care and other relevant service
      providers to identify the individual needs of disabled parents and provide
      adequate support throughout the pregnancy and after the child is born. Further
      research is important to clarify the exact nature of the associations for
      different types of maternal and child disability.

PMID- 24319278
TI  - Interactions between microfinance programmes and non-economic empowerment of
      women associated with intimate partner violence in Bangladesh: a cross-sectional
      study.
AB  - OBJECTIVE: This study aims to examine the associations between microfinance
      programme membership and intimate partner violence (IPV) in different
      socioeconomic strata of a nationally representative sample of women in
      Bangladesh. METHODS: The cross-sectional study was based on a nationally
      representative interview survey of 11 178 ever-married women of reproductive age
      (15-49 years). A total of 4465 women who answered the IPV-related questions were
      analysed separately using chi(2) tests and Cramer's V as a measure of effect size
      to identify the differences in proportions of exposure to IPV with regard to
      microfinance programme membership, and demographic variables and interactions
      between microfinance programme membership and factors related to non-economic
      empowerment were considered. RESULTS: Only 39% of women were members of
      microfinance programmes. The prevalence of a history of IPV was 48% for moderate
      physical violence, 16% for severe physical violence and 16% for sexual violence.
      For women with secondary or higher education, and women at the two wealthiest
      levels of the wealth index, microfinance programme membership increased the
      exposure to IPV two and three times, respectively. The least educated and poorest
      groups showed no change in exposure to IPV associated with microfinance
      programmes. The educated women who were more equal with their spouses in their
      family relationships by participating in decision-making increased their exposure
      to IPV by membership in microfinance programmes. CONCLUSIONS: Microfinance plans
      are associated with an increased exposure to IPV among educated and empowered
      women in Bangladesh. Microfinance firms should consider providing information
      about the associations between microfinance and IPV to the women belonging to the
      risk groups.

PMID- 24319279
TI  - Suitability of emergency department attenders to be assessed in primary care:
      survey of general practitioner agreement in a random sample of triage records
      analysed in a service evaluation project.
AB  - OBJECTIVES: To assess the proportion of emergency department (ED) attendances
      that would be suitable for primary care and the inter-rater reliability of
      general practitioner (GP) assessment of primary care suitability. DESIGN OF
      STUDY: Survey of GPs' agreement of suitability for primary care on a random
      anonymised sample of all ED patients attending over a 1-month period. SETTING: ED
      of a UK Hospital serving a population of 600 000. METHOD: Four GPs independently
      used data extracted from clinical notes to rate the appropriateness for
      management in primary care as well as need for investigations, specialist review
      or admission. Agreement was assessed using Cohen's kappa. RESULTS: The mean
      percentage of patients that GPs considered suitable for primary care management
      was 43% (range 38-47%). The kappa for agreement was 0.54 (95% CI 0.44 to 0.64)
      and 0.47(95% CI 0.38 to 0.59). In patients deemed not suitable for primary care,
      GPs were more likely to determine the need for specialist review (relative risks
      (RR)=3.5, 95% CI 3.0 to 4.2, p<0.001) and admission (RR=3.9, 95% CI 3.2 to 4.7,
      p<0.001). In patients assessed as suitable for primary care, GPs would initiate
      investigations in 51% of cases. Consensus over primary care appropriateness was
      higher for paediatric than for adult attenders. CONCLUSIONS: A significant number
      of patients attending ED could be managed by GPs, including those requiring
      investigations at triage. A stronger agreement among GPs over place of care may
      be seen for paediatric than for adult attenders. More effective signposting of
      patients presenting with acute or urgent problems and supporting a greater role
      for primary care in relieving the severe workflow pressures in ED in the UK are
      potential solutions.

PMID- 24319280
TI  - Assisting a child with tuberous sclerosis complex (TSC): a qualitative deep
      analysis of parents' experience and caring needs.
AB  - OBJECTIVE: This study was aimed to explore parents' experience of assisting
      children affected by tuberous sclerosis complex (TSC) with subependymal giant
      cell astrocytoma (SEGA) manifestation, in order to understand their caring needs
      and expectation of support. SETTING AND PROCEDURE: The study was designed
      according to the qualitative method of interpretative description and implied two
      sequential phases of data collection. The first phase was based on in-depth
      interviews with 18 Italian caregivers of children living with TSC. The second
      phase of the research was based on an online forum with 30 caregivers of children
      living with TSC. PARTICIPANTS: 48 Italian caregivers, assisting patients with TSC
      with SEGA manifestation have been involved in the study. RESULTS: When a TSC
      diagnosis is made, the whole family is affected psychologically. TSC has a great
      impact on families' quality of life and on their ability to cope with the disease
      and support the child's ability to recover and reach an acceptable level of well
      being. Caregivers report the experience of losing control and the feeling of
      loneliness and abandon from the healthcare system. CONCLUSION AND PRACTICE
      IMPLICATIONS: Families of children affected by TSC need targeted psychosocial
      assistance in order to support patients and caregivers and facilitate their
      social integration.

PMID- 24319281
TI  - Comment on "Reduced T-dependent humoral immunity in CD20-deficient mice".

PMID- 24319282
TI  - Calcineurin inhibitors: 40 years later, can't live without ...
AB  - Calcineurin inhibitors (CNIs) revolutionized the field of organ transplantation
      and remain the standard of care 40 years after the discovery of cyclosporine. The
      early impressive results of cyclosporine in kidney transplant recipients led to
      its subsequent use in other organ transplant recipients and for treatment of a
      variety of autoimmune diseases as well. In this review, we examine the discovery
      of CNIs, their mechanism of action, preclinical and clinical studies with CNIs,
      and the usage of CNIs in nontransplant recipients. We review the mechanisms of
      renal toxicity associated with CNIs and the recent efforts to avoid or reduce
      usage of these drugs. Although minimization strategies are possible, safe, and of
      potential long-term benefit, complete avoidance of CNIs has proven to be more
      challenging than initially thought. 

PMID- 24319284
TI  - Prevalence of cervical and oral human papillomavirus infections among US women.
AB  - Data from the National Health and Nutrition Examination Survey, 2009-2010,
      indicated that the prevalence of human papillomavirus (HPV) infection among women
      was 42.7% in the cervix and 3.8% in the oral cavity. The prevalence of oral HPV
      infection was 5-fold higher among women with than among those without cervical
      HPV infection (7.0% vs 1.4%; prevalence ratio, 4.9 [95% confidence interval, 2.7
      8.7]). Among the 3% of women with HPV detected at both sites, complete type
      concordance was detected in 6.6%, and partial agreement was detected in 37.7%.
      These data suggest that HPV infections at these 2 sites are not independent,
      although type-specific concordance is low. 

PMID- 24319285
TI  - Technical advance: monitoring the trafficking of neutrophil granulocytes and
      monocytes during the course of tissue inflammation by noninvasive 19F MRI.
AB  - Inflammation results in the recruitment of neutrophils and monocytes, which is
      crucial for the healing process. In the present study, we used (19)F MRI to
      monitor in vivo the infiltration of neutrophils and monocytes from the onset of
      inflammation to the resolution and healing phase. Matrigel, with or without LPS,
      was s.c.-implanted into C57BL/6 mice. This resulted in a focal inflammation
      lasting over a period of 20 days, with constantly decreasing LPS levels in doped
      matrigel plugs. After i.v. administration of (19)F containing contrast agent,
      (19)F MRI revealed a zonular (19)F signal in the periphery of LPS containing
      matrigel plugs, which was not observed in control plugs. Analysis of the (19)F
      signal over the observation period demonstrated the strongest (19)F signal after
      24 h, which decreased to nearly zero after 20 days. The (19)F signal was mirrored
      by the amount of leukocytes in the matrigel, with neutrophils dominating at early
      time-points and macrophages at later time-points. Both populations were shown to
      take up the (19)F contrast agent. In conclusion, (19)F MRI, in combination with
      the matrigel/LPS model, permits the noninvasive analysis of neutrophil and
      monocyte infiltration over the complete course of inflammation in vivo. 

PMID- 24319286
TI  - Modification of heparanase gene expression in response to conditioning and LPS
      treatment: strong correlation to rs4693608 SNP.
AB  - Heparanase is an endo-beta-glucuronidase that specifically cleaves the saccharide
      chains of HSPGs, important structural and functional components of the ECM.
      Cleavage of HS leads to loss of the structural integrity of the ECM and release
      of HS-bound cytokines, chemokines, and bioactive angiogenic- and growth-promoting
      factors. Our previous study revealed a highly significant correlation of HPSE
      gene SNPs rs4693608 and rs4364254 and their combination with the risk of
      developing GVHD. We now demonstrate that HPSE is up-regulated in response to
      pretransplantation conditioning, followed by a gradual decrease thereafter.
      Expression of heparanase correlated with the rs4693608 HPSE SNP before and after
      conditioning. Moreover, a positive correlation was found between recipient and
      donor rs4693608 SNP discrepancy and the time of neutrophil and platelet recovery.
      Similarly, the discrepancy in rs4693608 HPSE SNP between recipients and donors
      was found to be a more significant factor for the risk of aGVHD than patient
      genotype. The rs4693608 SNP also affected HPSE gene expression in LPS-treated
      MNCs from PB and CB. Possessors of the AA genotype exhibited up-regulation of
      heparanase with a high ratio in the LPS-treated MNCs, whereas individuals with
      genotype GG showed down-regulation or no effect on HPSE gene expression. HPSE up
      regulation was mediated by TLR4. The study emphasizes the importance of rs4693608
      SNP for HPSE gene expression in activated MNCs, indicating a role in allogeneic
      stem cell transplantation, including postconditioning, engraftment, and GVHD. 

PMID- 24319287
TI  - Negative role of inducible PD-1 on survival of activated dendritic cells.
AB  - PD-1 is a well-established negative regulator of T cell responses by inhibiting
      proliferation and cytokine production of T cells via interaction with its
      ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), expressed on non-T cells. Recently, PD
      1 was found to be expressed in innate cells, including activated DCs, and plays
      roles in suppressing production of inflammatory cytokines. In this study, we
      demonstrate that PD-1 KO DCs exhibited prolonged longevity compared with WT DCs
      in the dLNs after transfer of DCs into hind footpads. Interestingly, upon LPS
      stimulation, WT DCs increased the expression of PD-1 and started to undergo
      apoptosis. DCs, in spleen of LPS-injected PD-1 KO mice, were more resistant to
      LPS-mediated apoptosis in vivo than WT controls. Moreover, treatment of blocking
      anti-PD-1 mAb during DC maturation resulted in enhanced DC survival, suggesting
      that PD-1:PD-L interactions are involved in DC apoptosis. As a result, PD-1
      deficient DCs augmented T cell responses in terms of antigen-specific IFN-gamma
      production and proliferation of CD4 and CD8 T cells to a greater degree than WT
      DCs. Moreover, PD-1 KO DCs exhibited increased MAPK1 and CD40-CD40L signaling,
      suggesting a possible mechanism for enhanced DC survival in the absence of PD-1
      expression. Taken together, our findings further extend the function of PD-1,
      which plays an important role in apoptosis of activated DCs and provides
      important implications for PD-1-mediated immune regulation. 

PMID- 24319288
TI  - Characterization of endocannabinoid-mediated induction of myeloid-derived
      suppressor cells involving mast cells and MCP-1.
AB  - Endocannabinoids are lipid-signaling molecules found in the nervous system;
      however, their precise role in the periphery is unclear. In the current study, we
      observed that a single i.p. administration of AEA caused rapid induction of
      MDSCs. The MDSCs contained a mixture of granulocytic and monocytic subtypes and
      expressed Arg-1 and iNOS. The MDSCs suppressed T cell proliferation in vitro and
      used iNOS to mediate their effect. Moreover, adoptive transfer of MDSCs led to
      suppression of mBSA-induced DTH. Through the use of pharmacological inhibition,
      as well as genetic knockout mice, we found that the induction of MDSCs by AEA was
      CB1-dependent. The induction of MDSCs by AEA was reduced significantly in mast
      cell-deficient mice, while maintained in LPS-insensitive mice, showing that the
      induction of MDSCs by AEA was dependent, at least in part, on mast cells and
      independent of TLR4. Chemokine analysis of AEA- treated WT mice showed an early
      spike of MCP-1, which was decreased in Kit(W/W-sh) mice, showing a role of mast
      cells in the secretion of MCP-1 in response to AEA. Also, use of antibodies
      against MCP-1 or mice deficient in MCP-1 confirmed the role played by MCP-1.
      Interestingly, MCP-1 played a significant role in the induction of monocytic but
      not granulocytic MDSCs. Our studies demonstrate for the first time that
      endocannaboinids activate CB1 on mast cells to induce MCP-1, which facilitates
      recruitment of monocytic MDSCs. 

PMID- 24319289
TI  - The double bromodomain protein Brd2 promotes B cell expansion and mitogenesis.
AB  - Bromodomain-containing transcriptional regulators represent new epigenetic
      targets in different hematologic malignancies. However, bromodomain-mediated
      mechanisms that couple histone acetylation to transcription in lymphopoiesis and
      govern mature lymphocyte mitogenesis are poorly understood. Brd2, a
      transcriptional coregulator that contains dual bromodomains and an extraterminal
      domain (the BET family), couples chromatin to cell-cycle progression. We reported
      previously the first functional characterization of a BET protein as an effector
      of mammalian mitogenic signal transduction: EMU-Brd2 Tg mice develop "activated B
      cell" diffuse large B cell lymphoma. No other animal models exist for genetic or
      lentiviral expression of BET proteins, hampering testing of novel anti-BET
      anticancer drugs, such as JQ1. We transduced HSCs with Brd2 lentivirus and
      reconstituted recipient mice to test the hypothesis that Brd2 regulates
      hematopoiesis in BM and mitogenesis in the periphery. Forced expression of Brd2
      provides an expansion advantage to the donor-derived B cell compartment in BM and
      increases mature B cell mitogenic responsiveness in vitro. Brd2 binds the cyclin
      A promoter in B cells, shown by ChIP, and increases cyclin A mRNA and protein
      levels, and S-phase progression in vitro in mitogen-stimulated primary B cells,
      but not T cells, reinforcing results from EMU-Brd2 mice. The small molecule BET
      inhibitor JQ1 reduces B cell mitogenesis, consistent with the interpretation that
      BET inhibitors are antiproliferative. Brd2-specific knockdown experiments show
      that Brd2 is also required for hematopoiesis. We conclude that Brd2 plays a
      critical, independent role in regulation of mitogenic response genes,
      particularly cyclin A, in B cells. 

PMID- 24319290
TI  - 7alpha-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid reflects the
      integrity of the blood-brain barrier.
AB  - There is a continuous flux of the oxysterol 27-hydroxycholesterol (27-OHC) from
      the circulation across the blood-brain barrier (BBB) into the brain. The major
      metabolite of 27-OHC in the brain is 7alpha-hydroxy-3-oxo-4-cholestenoic acid (7
      HOCA). We confirm a recent report describing the presence of this metabolite in
      cerebrospinal fluid (CSF) at a relatively high concentration. A simple and
      accurate method was developed for assay of 7-HOCA in CSF based on isotope
      dilution-mass spectrometry and use of (2)H4-labeled internal standard. The
      concentration of this metabolite was found to be markedly increased in CSF from
      patients with a dysfunctional BBB. There was a high correlation between the
      levels of 7-HOCA in CSF and the CSF/serum albumin ratio. The concentration of 7
      HOCA in CSF was not significantly affected by neurodegeneration. Our findings
      suggest that 7-HOCA could be used as a diagnostic marker for conditions with a
      dysfunctional BBB. 

PMID- 24319291
TI  - KIF1C mutations in two families with hereditary spastic paraparesis and
      cerebellar dysfunction.
AB  - BACKGROUND: Hereditary spastic paraparesis (HSP) (syn. Hereditary spastic
      paraplegia, SPG) are a group of genetic disorders characterised by spasticity of
      the lower limbs due to pyramidal tract dysfunction. Nearly 60 disease loci have
      been identified, which include mutations in two genes (KIF5A and KIF1A) that
      encode motor proteins of the kinesin superfamily. Here we report a novel genetic
      defect in KIF1C of patients with spastic paraparesis and cerebellar dysfunction
      in two consanguineous families of Palestinian and Moroccan ancestry. METHODS AND
      RESULTS: We performed autozygosity mapping in a Palestinian and classic linkage
      analysis in a Moroccan family and found a locus on chromosome 17 that had
      previously been associated with spastic ataxia type 2 (SPAX2, OMIM %611302).
      Whole-exome sequencing revealed two homozygous mutations in KIF1C that were
      absent among controls: a nonsense mutation (c.2191C>T, p.Arg731*) that segregated
      with the disease phenotype in the Palestinian kindred resulted in the entire
      absence of KIF1C protein from the patient's fibroblasts, and a missense variant
      (c.505C>T, p.Arg169Trp) affecting a conserved amino acid of the motor domain that
      was found in the Moroccan kindred. CONCLUSIONS: Kinesin genes encode a family of
      cargo/motor proteins and are known to cause HSP if mutated. Here we identified
      nonsense and missense mutations in a further member of this protein family. The
      KIF1C mutation is associated with a HSP subtype (SPAX2/SAX2) that combines
      spastic paraplegia and weakness with cerebellar dysfunction.

PMID- 24319293
TI  - A self-normalized confidence interval for the mean of a class of nonstationary
      processes.
AB  - We construct an asymptotic confidence interval for the mean of a class of
      nonstationary processes with constant mean and time-varying variances. Due to the
      large number of unknown parameters, traditional approaches based on consistent
      estimation of the limiting variance of sample mean through moving block or non
      overlapping block methods are not applicable. Under a block-wise asymptotically
      equal cumulative variance assumption, we propose a self-normalized confidence
      interval that is robust against the nonstationarity and dependence structure of
      the data. We also apply the same idea to construct an asymptotic confidence
      interval for the mean difference of nonstationary processes with piecewise
      constant means. The proposed methods are illustrated through simulations and an
      application to global temperature series.

PMID- 24319292
TI  - The role of behavioural heterogeneity on infection patterns: implications for
      pathogen transmission.
AB  - Animals infected with pathogens often differ in behaviour from their uninfected
      counterparts, and these differences may be key to understanding zoonotic pathogen
      transmission. To explore behavioural heterogeneity and its role in pathogen
      transmission, we studied deer mice, Peromyscus maniculatus, under field
      conditions. Deer mice are the natural host of Sin Nombre virus (SNV), a zoonotic
      pathogen with high human mortality. We live-trapped mice in May, July and
      September of 2009 and 2010, marked captures with passive integrated transponder
      (PIT) tags, recorded physical characteristics and collected blood samples for SNV
      analysis. For 4 nights after each trapping session, we observed behaviour with a
      novel surveillance system of nine camera stations, each consisting of a foraging
      tray, infrared camera, PIT antenna and data logger. We found that deer mice
      infected with SNV (30.0%) engaged more frequently in behaviours that increased
      the probability of intraspecific encounters and SNV transmission than did
      uninfected deer mice. When deer mice were categorized as bold (31.7%) or shy
      (68.3%) based on these behaviours, bold behaviour was predictive of positive SNV
      status. Bold deer mice were three times more likely to be infected with SNV than
      were shy deer mice. These results suggest that a small percentage of bold
      individuals are responsible for a majority of SNV transmission events, and that
      behavioural phenotype is an important consideration in transmission dynamics of
      zoonotic diseases.

PMID- 24319294
TI  - Mathematics is differentially related to reading comprehension and word decoding:
      Evidence from a genetically-sensitive design.
AB  - Although evidence suggests that individual differences in reading and mathematics
      skills are correlated, this relationship has typically only been studied in
      relation to word decoding or global measures of reading. It is unclear whether
      mathematics is differentially related to word decoding and reading comprehension.
      The current study examined these relationships at both a phenotypic and
      etiological level in a population-based cohort of 5162 twin pairs at age 12.
      Multivariate genetic analyses of latent phenotypic factors of mathematics, word
      decoding and reading comprehension revealed substantial genetic and shared
      environmental correlations among all three domains. However, the phenotypic and
      genetic correlations between mathematics and reading comprehension were
      significantly greater than between mathematics and word decoding. Independent of
      mathematics, there was also evidence for genetic and nonshared environmental
      links between word decoding and reading comprehension. These findings indicate
      that word decoding and reading comprehension have partly distinct relationships
      with mathematics in the middle school years.

PMID- 24319295
TI  - Indirect Effects of the Family Check-Up on School-Age Academic Achievement
      Through Improvements in Parenting in Early Childhood.
AB  - This project examined the hypothesis that the impact of the Family Check-Up on
      parent use of positive behavior support would indirectly improve academic
      achievement scores at school age. The study included a sample of 731 high-risk
      families recruited from Women, Infant, and Children Supplemental Nutrition
      Program settings in 3 geographically distinct areas. The results demonstrated
      that changes in positive parenting between the child ages of 2 and 3 were
      associated with higher scores on children's school-age academic achievement, as
      measured by the Woodcock-Johnson III (W-J) Academic Skills composite. Moreover,
      structural equation modeling revealed that random assignment to the intervention
      was associated with higher levels of children's academic achievement at age 5 and
      age 7.5 indirectly, through greater increases in parents' use of positive
      behavior support in intervention families than in control families. Results are
      discussed with respect to the potential of a brief parenting intervention for
      improving parenting practices that promote academic achievement up to 5 years
      later. The results have promising implications for efforts to promote child
      adaptation in the school environment.

PMID- 24319296
TI  - Dating Relationships in Older Adulthood: A National Portrait.
AB  - Dating in later life is likely common, especially as the proportion of older
      adults who are single continues to rise. Yet there are no recent national
      estimates of either the prevalence or factors associated with dating during older
      adulthood. Using data from the 2005-2006 National Social Life, Health, and Aging
      Project, a nationally representative sample of 3,005 individuals ages 57-85, the
      authors constructed a national portrait of older adult daters. Roughly 14% of
      singles were in a dating relationship. Dating was more common among men than
      women and declined with age. Compared to non-daters, daters were more socially
      advantaged. Daters were more likely to be college educated and had more assets,
      were in better health, and reported more social connectedness. This study
      underscores the importance of new research on partnering in later life,
      particularly with the aging of the U.S. population and the swelling ranks of
      older singles.

PMID- 24319298
TI  - Enantioselective synthesis of (10S)- and (10R)-methyl-anandamides.
AB  - For the development of novel endocannabinoid templates with potential resistance
      to hydrolytic and oxidative metabolism, we are targeting the bis-allylic carbons
      of the arachidonoyl skeleton. Toward this end, we recently disclosed the
      synthesis and preliminary biological data for the (13S)-methyl-anandamide. We
      report now the total synthesis of the (10S)- and (10R)-methyl-counterparts. Our
      synthetic approach is stereospecific, efficient, and provides the analogs without
      the need for resolution. Peptide coupling, P-2 nickel partial hydrogenation, and
      cis-selective Wittig olefination are the key steps.

PMID- 24319299
TI  - Does Raising the Early Retirement Age Increase Employment of Older Workers?
AB  - Two pension reforms in Austria increased the early retirement age (ERA) from 60
      to 62 for men and from 55 to 58.25 for women. We find that raising the ERA
      increased employment by 9.75 percentage points among affected men and by 11
      percentage points among affected women. The reforms had large spillover effects
      on the unemployment insurance program but negligible effects on disability
      insurance claims. Specifically, unemployment increased by 12.5 percentage points
      among men and by 11.8 percentage points among women. The employment response was
      largest among high-wage and healthy workers, while low-wage and less healthy
      workers either continued to retire early via disability benefits or bridged the
      gap to the ERA via unemployment benefits. Taking spillover effects and additional
      tax revenues into account, we find that for a typical birth-year cohort a one
      year increase in the ERA resulted in a reduction of net government expenditures
      of 107 million euros for men and of 122 million euros for women.

PMID- 24319300
TI  - Stabilities of the Divalent Metal Ion Complexes of a Short-Chain Polyphosphate
      Anion and Its Imino Derivative.
AB  - ABSTRACT: The stability constants of ML-type complexes of the two linear
      triphosphate ligand anion analogues triphosphate ([Formula: see text]) and
      diimidotriphosphate ([Formula: see text]) were investigated thermodynamically
      using potentiometric titrations according to Schwarzenbach's procedure. The
      stability constants of the ML-type complexes of different divalent metal ions
      with [Formula: see text] are larger than those of the corresponding complexes
      with [Formula: see text] because of the greater basicity of the imino group. The
      order of the stability constants for the ML-type complexes follows the Irving
      Williams order, indicating that only non-bridging oxygen atoms are coordinated
      directly to the different metal ions in both ligands, and that the imino groups
      cannot participate in coordination to the metal ions. In the complexation
      reactions of the Ca2+, Sr2+, Ba2+-[Formula: see text] and Cu2+, Zn2+, Ni2+
      [Formula: see text] systems, each metal ion forms an enthalpically stable
      complex, and there was no suggestion of a conspicuous entropic effect based on
      the chelate effect. Monodentate complexes that are strongly coordinated with the
      ligands were therefore formed, whereas entropically stable bidentate complexes
      were formed in the complexation reactions of the Cu2+, Zn2+, Ni2+-[Formula: see
      text] and Ca2+, Ba2+, Sr2+-[Formula: see text] systems. According to the HSAB
      concept, hard metal cations such as Ca2+, Ba2+ and Sr2+ should bind to the harder
      oxygen atoms rather than the softer nitrogen atoms of the imidopolyphosphate
      anions, preventing direct coordination to the imino nitrogen atom. GRAPHICAL
      ABSTRACT: 

PMID- 24319297
TI  - Life-Threatening Disparities: The Treatment of Black and White Cancer Patients.
AB  - Cancer mortality and survival rates are much poorer for Black patients than for
      White patients. We argue that Black-White treatment disparities are a major
      reason for these disparities. We examine three specific kinds of Black-White
      treatment disparities: disparities in information exchange in oncology
      interactions, disparities in the treatment of breast cancer, and disparities in
      the treatment of clinically localized prostate cancer. In the final section, we
      discuss possible causes of these disparities, with a primary focus on
      communication within medical interactions and the role that race-related
      attitudes and beliefs may play in the quality of communication in these
      interactions.

PMID- 24319301
TI  - Modelling of the Critical Micelle Concentration of Cationic Gemini Surfactants
      Using Molecular Connectivity Indices.
AB  - Modelling of the critical micelle concentrations (cmc) using the molecular
      connectivity indices was performed for a set of 21 cationic gemini surfactants
      with medium-length spacers. The obtained model contains only the second-order
      Kier and Hall molecular connectivity index. It is suggested that the index 2chi
      includes some information about flexibility. The obtained model was used to
      predict log10 cmc of other cationic gemini surfactants. The agreement between
      calculated and experimental values of log10 cmc for the gemini surfactants that
      were not used in the correlation is very good.

PMID- 24319302
TI  - Solubility of Omeprazole Sulfide in Different Solvents at the Range of 280.35
      319.65 K.
AB  - Solubility data were measured for omeprazole sulfide in ethanol, 95 mass-%
      ethanol, ethyl acetate, isopropanol, methanol, acetone, n-butanol and n-propanol
      in the temperature range from 280.35 to 319.65 K by employing the gravimetric
      method. The solubilities increase with temperature and they are in good agreement
      with the calculated solubility of the modified Apelblat equation and the lambdah
      equation. The experimental solubility and correlation equation in this work can
      be used as essential data and model in the purification process of omeprazole
      sulfide. The thermodynamic properties of the solution process, including the
      Gibbs energy, enthalpy, and entropy were calculated using the van't Hoff
      equation.

PMID- 24319303
TI  - Latent Supervised Learning.
AB  - A new machine learning task is introduced, called latent supervised learning,
      where the goal is to learn a binary classifier from continuous training labels
      which serve as surrogates for the unobserved class labels. A specific model is
      investigated where the surrogate variable arises from a two-component Gaussian
      mixture with unknown means and variances, and the component membership is
      determined by a hyperplane in the covariate space. The estimation of the
      separating hyperplane and the Gaussian mixture parameters forms what shall be
      referred to as the change-line classification problem. A data-driven sieve
      maximum likelihood estimator for the hyperplane is proposed, which in turn can be
      used to estimate the parameters of the Gaussian mixture. The estimator is shown
      to be consistent. Simulations as well as empirical data show the estimator has
      high classification accuracy.

PMID- 24319304
TI  - Intervention Effects on Morning and Stimulated Cortisol Responses Among Toddlers
      in Foster Care.
AB  - Toddlers in child welfare often have a dysregulated stress response. We tested
      whether toddlers with caregivers randomized to a 10-week attachment-based
      intervention, Promoting First Relationships (PFR; Kelly, Sandoval, Zuckerman, &
      Buehlman, 2008) would show post-intervention change in stimulated salivary
      cortisol patterns during a research home visit involving a separation-reunion
      procedure, compared to a condition including child development and resource
      advice, but no attachment strategies. At baseline and post intervention, toddlers
      with a caregiver change within 7 weeks of enrollment (n=48, age 10-25 months)
      provided 4 saliva samples during a 1.5-hour research visit, and samples the next
      morning. The categorical dependent variable was the pattern of cortisol activity
      during the course of the post-intervention research visit: Flat, Decreasing,
      Increasing. Multinomial logistic regression was used to test for post
      intervention group differences in cortisol patterns, controlling for time of day,
      child's age, morning cortisol level, and baseline cortisol pattern. At baseline
      and post-intervention 92% of children demonstrated atypically low morning
      cortisol (< .21 ig/dL); Post-intervention, Flat, Decreasing and Increasing
      patterns were exhibited by 70%, 15%, and 15% of the sample, respectively.
      Significantly more children in the PFR condition showed an Increasing pattern.
      This may signal an intervention effect on separation-based stress response
      physiology.

PMID- 24319305
TI  - A large area, silicon photomultiplier-based PET detector module.
AB  - The introduction of silicon photomultipliers (SiPM) has facilitated construction
      of compact, efficient and magnetic field-hardened positron emission tomography
      (PET) scanners. To take full advantage of these devices, methods for using them
      to produce large field-of-view PET scanners are needed. In this investigation, we
      explored techniques to combine two SiPM arrays to form the building block for a
      small animal PET scanner. The module consists of a 26 * 58 array of 1.5 * 1.5mm2
      LYSO elements (spanning 41 * 91mm2) coupled to two SensL SiPM arrays. The SiPMs
      were read out with new multiplexing electronics developed for this project. To
      facilitate calculation of event position with multiple SiPM arrays it was
      necessary to spread scintillation light amongst a number of elements with a small
      light guide. This method was successful in permitting identification of all
      detector elements, even at the seam between two SiPM arrays. Since the
      performance of SiPMs is enhanced by cooling, the detector module was fitted with
      a cooling jacket, which allowed the temperature of the device and electronics to
      be controlled. Testing demonstrated that the peak-to-valley contrast ratio of the
      light detected from the scintillation array was increased by ~45% when the
      temperature was reduced from 28  degrees C to 16  degrees C. Energy resolution
      for 511 keV photons improved slightly from 18.8% at 28  degrees C to 17.8% at 16 
      degrees C. Finally, the coincidence timing resolution of the module was found to
      be insufficient for time-of-flight applications (~2100 ps at 14  degrees C). The
      first use of these new modules will be in the construction of a small animal PET
      scanner to be integrated with a 3T clinical magnetic resonance imaging scanner.

PMID- 24319306
TI  - Conditional Cash Transfers and HIV/AIDS Prevention: Unconditionally Promising?
AB  - Conditional cash transfers (CCT) have recently received considerable attention as
      a potentially innovative and effective approach to the prevention of HIV/AIDS. We
      evaluate a conditional cash transfer program in rural Malawi which offered
      financial incentives to men and women to maintain their HIV status for
      approximately one year. The amounts of the reward ranged from zero to
      approximately 3-4 months wage. We find no effect of the offered incentives on HIV
      status or on reported sexual behavior. However, shortly after receiving the
      reward, men who received the cash transfer were 9 percentage points more likely
      and women were 6.7 percentage points less likely to engage in risky sex. Our
      analyses therefore question the "unconditional effectiveness" of CCT program for
      HIV prevention: CCT Programs that aim to motivate safe sexual behavior in Africa
      should take into account that money given in the present may have much stronger
      effects than rewards offered in the future, and any effect of these programs may
      be fairly sensitive to the specific design of the program, the local and/or
      cultural context, and the degree of agency an individual has with respect to
      sexual behaviors.

PMID- 24319307
TI  - The Relationship of Error Rate and Comprehension in Second and Third Grade Oral
      Reading Fluency.
AB  - This study explored the relationships of oral reading speed and error rate on
      comprehension with second and third grade students with identified reading risk.
      The study included 920 2nd graders and 974 3rd graders. Participants were
      assessed using Dynamic Indicators of Basic Early Literacy Skills (DIBELS) and the
      Woodcock Reading Mastery Test (WRMT) Passage Comprehension subtest. Results from
      this study further illuminate the significant relationships between error rate,
      oral reading fluency, and reading comprehension performance, and grade-specific
      guidelines for appropriate error rate levels. Low oral reading fluency and high
      error rates predict the level of passage comprehension performance. For second
      grade students below benchmark, a fall assessment error rate of 28% predicts that
      student comprehension performance will be below average. For third grade students
      below benchmark, the fall assessment cut point is 14%. Instructional implications
      of the findings are discussed.

PMID- 24319308
TI  - The Difficulty of Maintaining Positive Intervention Effects: A Look at Disruptive
      Behavior, Deviant Peer Relations, and Social Skills During the Middle School
      Years.
AB  - This paper examines the effects of the Fast Track preventive intervention on
      youths' functioning in three domains: disruptive behavior problems, involvement
      with deviant peers, and social skills during the middle school years. Eight
      hundred ninety-one children had been randomly assigned by sets of schools within
      four sites to intervention (n = 445) or to control (n = 446) conditions. In
      contrast to prior findings of the effectiveness of the Fast Track intervention
      during the elementary school years, the current findings indicate that Fast Track
      had little overall impact on children's functioning in these domains during this
      age period. There were positive intervention effects on only 2 of 17 outcomes
      examined. Although the intervention had positive impact on children's hyperactive
      and self-reported delinquent behaviors in seventh grade, there were no
      intervention effects on other externalizing behavior problems or on social
      skills, and there was a negative intervention effect on children's involvement
      with deviant peers during this age period.

PMID- 24319309
TI  - Investigation of associations between obesity and LEP G2548A and LEPR 668A/G
      polymorphisms in a Turkish population.
AB  - OBJECTIVE: Obesity is a complex heterogeneous disease that is caused by genes,
      environmental factors, and the interaction between the two. The leptin (LEP) and
      leptin receptor (LEPR) genes have been evaluated for polymorphisms that could
      potentially be related to the pathophysiology of obesity and its complications.
      The aim of this study was to investigate the role of LEP G2548A and LEPR 668A/G
      polymorphisms in the pathogenesis of obesity. SUBJECTS: The study included 127
      patients with obesity and 105 healthy controls. Polymerase chain reaction and
      restriction fragment length analysis for LEP G2548A and LEPR 668A/G polymorphisms
      were applied. RESULTS: There was no statistically significant difference in the
      genotype frequencies of the LEP gene polymorphism between patients and control
      groups (P > 0.05). We found a difference in the LEPR genotypes between patients
      and controls, but this was not statistically significant (P = 0.05).
      Additionally, we found an increased risk of obesity in the LEP/LEPR GG/GG
      combined genotype (P < 0.05). CONCLUSION: Our findings indicate that the LEP
      G2548A polymorphism is not a relevant obesity marker and that the LEPR 668A/G
      polymorphism may be related to obesity in a Turkish population. Further
      researches with larger patient population are necessary to ascertain the
      implications of LEP and LEPR polymorphisms in obesity.

PMID- 24319310
TI  - Women as agents of change: Female income and mobility in India.
AB  - Economic globalization will give many women in developing countries access to
      steady and relatively remunerative employment for the first time, potentially
      shifting bargaining power within their households and changing the choices that
      are made for their children. This paper exploits a unique setting - a group of
      tea plantations in South India where women are employed in permanent wage labor
      and where incomes do not vary by caste - to anticipate the impact of
      globalization on mobility across social groups in the future. The main result of
      the paper is that a relative increase in female income weakens the family's ties
      to the ancestral community and the traditional economy, but these mobility
      enhancing effects are obtained for certain historically disadvantaged castes
      alone. Although the paper provides a context-specific explanation for why the
      women from these castes emerge as agents of change, the first general implication
      of the analysis is that the incentive and the ability of women to use their
      earnings to influence household decisions depends importantly on their social
      background. The second implication is that historically disadvantaged groups may,
      in fact, be especially responsive to new opportunities precisely because they
      have fewer ties to the traditional economy to hold them back.

PMID- 24319311
TI  - Marital Quality of Newlywed African American Couples: Implications of Egalitarian
      Gender Role Dynamics.
AB  - This research examined associations between husbands' and wives' gender role
      attitudes, division of household labor, and marital quality in a sample of 697
      newlywed African American couples residing in the southern region of the United
      States. Guided by a cultural ecological framework, we tested hypotheses specific
      to the unique socio-cultural context of African Americans using a mixed model
      ANCOVA design. Results revealed that: (1) couples reported lower marital quality
      when husbands had relatively more traditional gender role attitudes; (2) husbands
      reported lower marital quality when the couple engaged in a relatively more
      traditional division of household labor; and (3) husbands with more traditional
      attitudes who also engaged in a traditional division of labor reported lower
      marital quality compared to all other husbands. Although African Americans are
      thought to have more flexible gender role orientations than other racial/ethnic
      groups within the U.S., these results document within group variability in couple
      gender dynamics and its association with variability in marital quality.

PMID- 24319312
TI  - Palladium-Catalyzed Highly Regioselective C-3 Arylation of Imidazo[1,5
      a]pyridine.
AB  - A direct palladium-catalyzed highly regioselective C-3 arylation of imidazo[1,5
      a]pyridine with aryl bromides has been developed. This reaction is quite general
      with respect to the aryl or hetaryl bromide.

PMID- 24319313
TI  - Short-time quantum propagator and Bohmian trajectories.
AB  - We begin by giving correct expressions for the short-time action following the
      work Makri-Miller. We use these estimates to derive an accurate expression modulo
      [Formula: see text] for the quantum propagator and we show that the quantum
      potential is negligible modulo [Formula: see text] for a point source, thus
      justifying an unfortunately largely ignored observation of Holland made twenty
      years ago. We finally prove that this implies that the quantum motion is
      classical for very short times.

PMID- 24319314
TI  - Thermochemical and Vapor Pressure Behavior of Anthracene and Brominated
      Anthracene Mixtures.
AB  - The present work concerns the thermochemical and vapor pressure behavior of the
      anthracene (1) + 2-bromoanthracene (2) and anthracene (1) + 9-bromoanthracene (3)
      systems. Solid-liquid equilibrium temperature and differential scanning
      calorimetry studies indicate the existence of a minimum melting solid state near
      an equilibrium temperature of 477.65 K at x1 = 0.74 for the (1) + (2) system.
      Additionally, solid-vapor equilibrium studies for the (1) + (2) system show that
      the vapor pressure of the mixtures depends on composition, but does not follow
      ideal Raoult's law behaviour. The (1) + (3) system behaves differently from the
      (1) + (2) system. The (1) + (3) system has a solid solution like phase diagram.
      The system consists of two phases, an anthracene like phase and a 9
      bromoanthracene like phase, while (1) + (2) mixtures only form a single phase.
      Moreover, experimental studies of the two systems suggest that the (1) + (2)
      system is in a thermodynamically lower energy state than the (1) + (3) system.

PMID- 24319315
TI  - Assessing complexity of skin blood flow oscillations in response to locally
      applied heating and pressure in rats: implications for pressure ulcer risk.
AB  - The objective of this study was to investigate the effects of local heating on
      complexity of skin blood flow oscillations (BFO) under prolonged surface pressure
      in rats. Eleven Sprague-Dawley rats were studied: 7 rats underwent surface
      pressure with local heating (Deltat = 10  degrees C) and 4 rats underwent
      pressure without heating. A pressure of 700 mmHg was applied to the right
      trochanter area of rats for 3 h. Skin blood flow was measured using laser Doppler
      flowmetry. The loading period was divided into nonoverlapping 30 min epochs. For
      each epoch, multifractal detrended fluctuation analysis (MDFA) was utilized to
      compute DFA coefficients and complexity of endothelia related metabolic,
      neurogenic, and myogenic frequencies of BFO. The results showed that under
      surface pressure, local heating led to a significant decrease in DFA coefficients
      of myogenic frequency during the initial epoch of loading period, a sustained
      decrease in complexity of myogenic frequency, and a significantly higher degree
      of complexity of metabolic frequency during the later phase of loading period.
      Surrogate tests showed that the reduction in complexity of myogenic frequency was
      associated with a loss of nonlinearity whereas increased complexity of metabolic
      frequency was associated with enhanced nonlinearity. Our results indicate that
      increased metabolic activity and decreased myogenic response due to local heating
      manifest themselves not only in magnitudes of metabolic and myogenic frequencies
      but also in their structural complexity. This study demonstrates the feasibility
      of using complexity analysis of BFO to monitor the ischemic status of weight
      bearing skin and risk of pressure ulcers.

PMID- 24319316
TI  - Combined Individual Cognitive Behavior Therapy and Parent Training for Childhood
      Depression: 2-3-Year Follow-Up.
AB  - Fourteen children with significant depressive symptoms from an open clinical
      trial of Primary and Secondary Control Enhancement Training augmented with
      Caregiver-Child Relationship Enhancement Training, participated in a 2-3-year
      follow-up assessment. The results suggested that the significant decreases in
      depressive symptoms observed at post-treatment were maintained at 2-3-year follow
      up. Mothers' reports of significant improvement of child psychosocial functioning
      were also maintained, providing social validation of the effects. Pre-treatment
      child-rated mother-child relations predicted depressive symptoms at 2-3-year
      follow-up. These long-term data support the use of the combined intervention and
      suggest the need for further research on caregiver involvement in treatment.

PMID- 24319317
TI  - Bayesian network models in brain functional connectivity analysis.
AB  - Much effort has been made to better understand the complex integration of
      distinct parts of the human brain using functional magnetic resonance imaging
      (fMRI). Altered functional connectivity between brain regions is associated with
      many neurological and mental illnesses, such as Alzheimer and Parkinson diseases,
      addiction, and depression. In computational science, Bayesian networks (BN) have
      been used in a broad range of studies to model complex data set in the presence
      of uncertainty and when expert prior knowledge is needed. However, little is done
      to explore the use of BN in connectivity analysis of fMRI data. In this paper, we
      present an up-to-date literature review and methodological details of
      connectivity analyses using BN, while highlighting caveats in a real-world
      application. We present a BN model of fMRI dataset obtained from sixty healthy
      subjects performing the stop-signal task (SST), a paradigm widely used to
      investigate response inhibition. Connectivity results are validated with the
      extant literature including our previous studies. By exploring the link strength
      of the learned BN's and correlating them to behavioral performance measures, this
      novel use of BN in connectivity analysis provides new insights to the functional
      neural pathways underlying response inhibition.

PMID- 24319318
TI  - Acute Effects of Marijuana Smoking on Negative and Positive Affect.
AB  - Human studies and animal experiments present a complex and often contradictory
      picture of the acute impact of marijuana on emotions. The few human studies
      specifically examining changes in negative affect find either increases or
      reductions following delta-9-tetrahydrocannabinol (THC) administration. In a 2 *
      2, instructional set (told THC vs. told no THC) by drug administration (smoked
      marijuana with 2.8% THC vs. placebo) between-subjects design, we examined the
      pharmacologic effect of marijuana on physiological and subjective stimulation,
      subjective intoxication, and self-reported negative and positive affect with 114
      weekly marijuana smokers. Individuals were first tested under a baseline/no
      smoking condition and again under experimental condition. Relative to placebo,
      THC significantly increased arousal and confusion/bewilderment. However, the
      direction of effect on anxiety varied depending on instructional set: Anxiety
      increased after THC for those told placebo but decreased among other
      participants. Furthermore, marijuana users who expected more impairment from
      marijuana displayed more anxiety after smoking active marijuana, whereas those
      who did not expect the impairment became less anxious after marijuana. Both
      pharmacologic and stimulus expectancy main effects significantly increased
      positive affect. Frequent marijuana users were less anxious after smoking as
      compared to less frequent smokers. These findings show that expectancy
      instructions and pharmacology play independent roles in effects of marijuana on
      negative affect. Further studies examining how other individual difference
      factors impact marijuana's effects on mood are needed.

PMID- 24319319
TI  - Resonant waveguide grating biosensor-enabled label-free and fluorescence
      detection of cell adhesion.
AB  - Cell adhesion to extracellular matrix (ECM) is fundamental to many distinct
      aspects of cell biology, and has been an active topic for label-free biosensors.
      However, little attention has been paid to study the impact of receptor signaling
      on the cell adhesion process. We here report the development of resonant
      waveguide grating biosensor-enabled label-free and fluorescent approaches, and
      their use for investigating the adhesion of an engineered HEK-293 cell line
      stably expressing green fluorescent protein (GFP) tagged beta2-adrenergic
      receptor (beta2-AR) onto distinct surfaces under both ambient and physiological
      conditions. Results showed that cell adhesion is sensitive to both temperature
      and ECM coating, and distinct mechanisms govern the cell adhesion process under
      different conditions. The beta2-AR agonists, but not its antagonists or partial
      agonists, were found to be capable of triggering signaling during the adhesion
      process, leading to an increase in the adhesion of the engineered cells onto
      fibronectin-coated biosensor surfaces. These results suggest that the dual
      approach presented is useful to investigate the mechanism of cell adhesion, and
      to identify drug molecules and receptor signaling that interfere with cell
      adhesion.

PMID- 24319320
TI  - Naphthalene Mothballs: Emerging and Recurring Issues and their Relevance to
      Environmental Health.
AB  - Naphthalene is a polycyclic aromatic hydrocarbon that is commonly encountered in
      indoor and outdoor environments. There is growing awareness of the environmental
      health risks associated with inhalation exposure to naphthalene in the indoor
      environment. While there are numerous potential sources of naphthalene indoors,
      the use of mothballs can be a significant contributor to ambient concentrations.
      This review article describes recurring and emerging environmental health issues
      relating to mothballs containing naphthalene. The toxicology and health effects
      of naphthalene exposure are reviewed, with discussion of high-risk populations
      and risk mitigation strategies. Environmental health professionals should be
      aware of mothball use in the home, and recognize risks associated with accidental
      exposure and misuse.

PMID- 24319321
TI  - Minority Stress Theory: An Examination of Factors Surrounding Sexual Risk
      Behavior among Gay & Bisexual Men Who Use Club Drugs.
AB  - BACKGROUND: Few studies have examined the impact of minority stress theory upon
      sexual risk behavior among gay and bisexual men using club drugs. Similar studies
      have focused on ethnic minorities and women, however gay and bisexual men
      demonstrate greater likelihood for risk behaviors leading to HIV/AIDS. OBJECTIVE:
      This study examined sexual risk behavior from the perspective of minority stress
      theory upon substance using gay and bisexual men and their partners. METHODS:
      Multivariable logistic regression analysis examined minority stress associations
      with participant sexual risk behaviors, drug use and partner type, controlling
      for demographics. RESULTS: 396 gay and 54 bisexual respondents, ages 18-67
      reported at least one time drug use while engaging in sexual risk behavior. In
      the adjusted model, expectations of rejection associated with lower odds of
      sexual risk behavior, while older age approached significance. CONCLUSIONS:
      Theoretical origins for examining risk behavior among gay and bisexual men may
      underscore risk and protective factors, while ultimately holding implications for
      prevention and treatment interventions.

PMID- 24319322
TI  - Diet Quality of Overweight and Obese Adults with Intellectual and Developmental
      Disabilities as Measured by the Healthy Eating Index-2005.
AB  - BACKGROUND: Little research has been conducted to examine diet quality of
      overweight and obese adults with intellectual and developmental disabilities
      (IDD) in the United States. The purpose of this study was to determine diet
      quality, as measured by the Healthy Eating Index-2005 (HEI-2005), of overweight
      and obese adults with IDD. METHODS: Data were obtained from community-dwelling
      overweight individuals. 3-day food records were administered and completed with
      assistance by staff or family members and then reviewed by a dietitian. All
      records were analyzed and HEI-2005 was calculated using NDSR output. RESULTS: 178
      records were analyzed from 70 subjects (28 male, 42 female; mean age 33.9 +/-11.5
      years). The mean energy intake was 1928 +/- 891 kcals and the mean total HEI-2005
      score was 46.7+/- 11.5. Participants scored the lowest in total fruits, whole
      grains, dark green and orange vegetables, non-hydrogenated vegetable oils, and
      sodium. Both male and females had diets deficient in fiber, vitamin A, vitamin D,
      vitamin E, folate, and potassium. Additionally men were deficient in vitamin K,
      and women were deficient in calcium. CONCLUSIONS: Overweight and Obese adults
      with IDD had a lower HEI-2005 score compared to the general population and are at
      an increased risk of poor diet quality and nutritional deficiencies that could
      contribute to the development of diabetes, cardiovascular disease, cancer and
      other health complications.

PMID- 24319323
TI  - Predictors of Response and Mechanisms of Change in an Organizational Skills
      Intervention for Students with ADHD.
AB  - The purpose of the study was to evaluate predictors of response and mechanisms of
      change for the Homework, Organization, and Planning Skills (HOPS) intervention
      for middle school students with Attention-Deficit/Hyperactivity Disorder (ADHD).
      Twenty-three middle school students with ADHD (grades 6-8) received the HOPS
      intervention implemented by school mental health providers and made significant
      improvements in parent-rated materials organization and planning skills,
      impairment due to organizational skills problems, and homework problems.
      Predictors of response examined included demographic and child characteristics,
      such as gender, ethnicity, intelligence, ADHD and ODD symptom severity, and ADHD
      medication use. Mechanisms of change examined included the therapeutic alliance
      and adoption of the organization and planning skills taught during the HOPS
      intervention. Participant implementation of the HOPS binder materials
      organization system and the therapeutic alliance as rated by the student
      significantly predicted post-intervention outcomes after controlling for pre
      intervention severity. Adoption of the binder materials organization system
      predicted parent-rated improvements in organization, planning, and homework
      problems above and beyond the impact of the therapeutic alliance. These findings
      demonstrate the importance of teaching students with ADHD to use a structured
      binder organization system for organizing and filing homework and classwork
      materials and for transferring work to and from school.

PMID- 24319324
TI  - Classification of Tumor Histology via Morphometric Context.
AB  - Image-based classification of tissue histology, in terms of different components
      (e.g., normal signature, categories of aberrant signatures), provides a series of
      indices for tumor composition. Subsequently, aggregation of these indices in each
      whole slide image (WSI) from a large cohort can provide predictive models of
      clinical outcome. However, the performance of the existing techniques is hindered
      as a result of large technical and biological variations that are always present
      in a large cohort. In this paper, we propose two algorithms for classification of
      tissue histology based on robust representations of morphometric context, which
      are built upon nuclear level morphometric features at various locations and
      scales within the spatial pyramid matching (SPM) framework. These methods have
      been evaluated on two distinct datasets of different tumor types collected from
      The Cancer Genome Atlas (TCGA), and the experimental results indicate that our
      methods are (i) extensible to different tumor types; (ii) robust in the presence
      of wide technical and biological variations; (iii) invariant to different nuclear
      segmentation strategies; and (iv) scalable with varying training sample size. In
      addition, our experiments suggest that enforcing sparsity, during the
      construction of morphometric context, further improves the performance of the
      system.

PMID- 24319326
TI  - Continuous-Time Proportional Hazards Regression for Ecological Monitoring Data.
AB  - We consider a continuous-time proportional hazards model for the analysis of
      ecological monitoring data where subjects are monitored at discrete times and
      fixed sites across space. Since the exact time of event occurrence is not
      directly observed, we rely on dichotomous event indicators observed at monitoring
      times to make inference about the model parameters. We use autoregression on the
      response at neighboring sites from a previous time point to take into account
      spatial dependence. The interesting fact is utilized that the probability of
      observing an event at a monitoring time when the underlying hazards is
      proportional falls under the class of generalized linear models with binary
      responses and complementary log-log link functions. Thus, a maximum likelihood
      approach can be taken for inference and the computation can be carried out using
      standard statistical software packages. This approach has significant
      computational advantages over some of the existing methods that rely on Monte
      Carlo simulations. Simulation experiments are conducted and demonstrate that our
      method has sound finite-sample properties. A real dataset from an ecological
      study that monitored bark beetle colonization of red pines in Wisconsin is
      analyzed using the proposed models and inference. Supplementary materials that
      contain technical details are available online.

PMID- 24319325
TI  - A novel opportunity in minimally invasive colorectal cancer therapy: defining a
      role for endoscopic submucosal dissection in the United States.
AB  - Colorectal cancer is the third most common cancer among both men and women in the
      United States and the second leading cause of cancer death. Endoscopic submucosal
      dissection (ESD) is an innovative advanced endoscopic therapy for superficial
      gastrointestinal neoplasms which is rapidly becoming standard of care
      particularly in Asia. ESD was first developed for the resection of early gastric
      cancers; yet ESD for colon tumors has gained increasing attention in recent
      years. The advantage of ESD over conventional endoscopic resection lies in its
      potential to achieve en bloc resection regardless of tumor size, leading to more
      precise histological evaluation and greater potential for cure. Selecting
      appropriate patients for this procedure involves identifying colorectal cancers
      with nul risk of lymph node spread. For colorectal ESD to engraft in the United
      States, the prevalence of such early stage lesions must be defined so that
      centers of excellence can be developed for high volume clinical practice to offer
      patients the safest and most efficacious outcomes. This review discusses the
      endoscopic staging of colorectal neoplasms, indications for colorectal ESD, and
      the epidemiology of early stage ESD-amenable colorectal cancer in America to
      better define an opportunity for this important minimally invasive therapy. 

PMID- 24319327
TI  - A novel donor splice-site mutation of major intrinsic protein gene associated
      with congenital cataract in a Chinese family.
AB  - PURPOSE: To identify the disease-causing gene in a Chinese family with autosomal
      dominant congenital cataract. METHODS: Clinical and ophthalmologic examinations
      were performed on all members of a Chinese family with congenital cataract. Nine
      genes associated with congenital cataract were screened using direct DNA
      sequencing. Mutations were confirmed using restriction fragment length
      polymorphism (RFLP) analysis. The mutated multi-intronic plasmid (MIP) minigene,
      which carries the disease-causing splice-site mutation, and the wild-type (WT)
      MIP minigene were constructed using the pcDNA3.1 expression vector. Wild-type and
      mutant MIP minigene constructs were transiently transfected into HeLa cells.
      After 48 h of incubation at 37  degrees C, total RNA isolation and reverse
      transcription (RT)-PCR analysis were performed, and PCR products were separated
      and confirmed with sequencing. RESULTS: Direct DNA sequence analysis identified a
      novel splice-site mutation in intron 3 (c.606+1 G>A) of the MIP gene. To
      investigate the manner in which the splice donor mutation could affect mRNA
      splicing, WT and mutant MIP minigenes were inserted in the pcDNA3.1 (+) vector.
      Constructs were transfected into HeLa cells. RT-PCR analysis showed that the
      donor splice site mutation led to deletion of exon 3 in the mRNA encoded by the
      MIP gene. CONCLUSIONS: The present study identified a novel donor splice-site
      mutation (c.606+1G>A) in the MIP gene in a Chinese family with congenital
      cataract. In vitro RT-PCR analysis showed that this splice-site mutation resulted
      in the deletion of exon 3 from mRNA encoded by the MIP gene. This is the first
      report to show that donor splice-site mutation in MIP genes can cause autosomal
      dominant congenital cataract.

PMID- 24319328
TI  - Point mutations associated with Leber hereditary optic neuropathy in a Latvian
      population.
AB  - PURPOSE: To study mutations associated with Leber hereditary optic neuropathy
      (LHON) in patients suspected of having this mitochondrial disorder in a Latvian
      population. Additional aims were to determine the heteroplasmy status of all non
      synonymous polymorphisms identified in the current study and to identify the
      mitochondrial haplogroups of the studied participants because these factors may
      contribute to the manifestation of LHON. METHODS: Twelve patients, including
      patients in two families, were enrolled in the current study. LHON was suspected
      based on the findings of ophthalmologic examinations. In clinically affected
      individuals, the presence of all previously reported LHON-associated mutations
      was assessed with sequencing analysis. Additionally, the SURVEYOR endonuclease
      assay was used to detect heteroplasmy. The mitochondrial haplogroups were
      identified with restriction analysis and the sequencing of hypervariable segment
      1. RESULTS: In one family (mother and son), there was one primary LHON-associated
      mutation, G11778A. In addition, one rare previously reported LHON-associated
      polymorphism, A13637G, was detected in two unrelated patients. A non-synonymous
      polymorphism at T6253C was found in one individual. This mutation was reported in
      the background of the 3460 mutation among LHON patients in a Chinese population.
      No non-synonymous point mutations in mitochondrial DNA were found in five of the
      study participants. CONCLUSIONS: Molecular analysis of 12 patients with suspected
      LHON confirmed the diagnosis in four patients and allowed the use of appropriate
      prophylactic measures and treatment. Further investigations and additional
      studies of different populations are necessary to confirm the role of the non
      synonymous polymorphisms A13637G and T6253C in the manifestation of LHON and the
      associations of these polymorphisms with mitochondrial haplogroups and
      heteroplasmy.

PMID- 24319329
TI  - Simple fixation and storage protocol for preserving the internal structure of
      intact human donor lenses and extracted human nuclear cataract specimens.
AB  - PURPOSE: Increased use of phacoemulsification procedures for cataract surgeries
      has resulted in a dramatic decrease in the availability of cataractous nuclear
      specimens for basic research into the mechanism of human cataract formation. To
      overcome such difficulties, a fixation protocol was developed to provide good
      initial fixation of human donor lenses and extracted nuclei, when available, and
      is suitable for storing or shipping cataracts to laboratories where structural
      studies could be completed. METHODS: Cataractous lens nuclei (n=19, ages 12 to 74
      years) were obtained from operating suites after extracapsular extraction.
      Transparent human donor lenses (n=27, ages 22 to 92 years) were obtained from the
      Ramayamma International Eye Bank. After the dimensions were measured with a
      digital caliper, samples were preserved in 10% formalin (neutral buffered) for 24
      h and followed by fixation in 4% paraformaldehyde (pH 7.2) for 48 h. Samples were
      stored cold (4  degrees C) in buffer until shipped. Samples were photographed and
      measured before further processing for transmission electron microscopy. RESULTS:
      The dimensions of the samples varied slightly after short fixation followed by 1
      to 5 months' storage before transmission electron microscopy processing. The mean
      change in the axial thickness of the donor lenses was 0.15+/-0.21 mm or 3.0+/
      5.4%, while that of the extracted nuclei was 0.05+/-0.24 mm or 1.8+/-7.6%.
      Because the initial concern was whether the nuclear core was preserved, thin
      sections were examined from the embryonic and fetal nuclear regions. All cellular
      structures were preserved, including the cytoplasm, complex edge processes,
      membranes, and junctions. The preservation quality was excellent and nearly
      equivalent to preservation of fresh lenses even for the lens cortex. Cell damage
      characteristic of specific nuclear cataract types was easily recognized.
      CONCLUSIONS: The novel fixation protocol appears effective in preserving whole
      donor lenses and cataractous nuclei over a wide age range. Dimensions varied only
      2%-3%, and fiber cell damage correlated well with standard fixation. These
      methods enable researchers and clinicians in remote settings to preserve donor
      lenses and rare examples of extracapsular extractions for detailed examination at
      later times.

PMID- 24319330
TI  - Role of hypoxia-inducible factor-1alpha in preconditioning-induced protection of
      retinal ganglion cells in glaucoma.
AB  - PURPOSE: We recently demonstrated in a mouse model of glaucoma that endogenous
      epigenetic mechanisms can be activated by a repetitive hypoxic preconditioning
      (RHP) stimulus to provide robust retinal ganglion cell (RGC) protection. Although
      we also provided evidence that RHP prevents or delays the apoptotic demise of the
      RGC soma, the mechanisms responsible for signaling this epigenetic response, as
      well as the effectors of the glaucoma-tolerant phenotype at the somatic and
      axonal levels, remain unidentified. In the present study, we used conditional
      mutant mice lacking hypoxia-inducible factor-1alpha (HIF-1alpha) in RGCs (HIF
      1alpha RGC-knockout [KO] mice) to test the hypothesis that RHP-mediated
      activation of this transcription factor in these cells protects them from
      glaucomatous injury. METHODS: Adult HIF-1alpha RGC-KO mice, generated by mating
      floxed HIF-1alpha mice with math5-Cre mice, were used. Experimental glaucoma was
      induced unilaterally in the HIF-1alpha RGC-KO mice and matched wild-types by
      elevating the intraocular pressure to 16-20 mmHg for 3 consecutive weeks,
      secondary to episcleral vein ligation. Mice of each genotype were randomized to
      either an RHP protocol (six total exposures to systemic hypoxia [11% oxygen],
      interspersed over a 2-week period, completed 3 days before ligation surgery) or
      to an untreated group. RGC soma and axon injury was quantified with Neuronal
      Nuclei (NeuN) immunohistochemistry in retinal flat mounts and SMI32
      immunohistochemistry in cross sections of the post-laminar optic nerve,
      respectively. RESULTS: HIF-1alpha RGC-KO mice exhibited normal retinal function
      and morphology, and crosses of math5-Cre mice with floxed ROSA26 reporter mice
      confirmed Cre recombinase activity was confined to the RGC axons and soma.
      Untreated wild-type mice exhibited a 30+/-2% loss of RGC soma and a 31+/-3% loss
      of RGC axons after 3 weeks of intraocular hypertension (both p<0.05 versus fellow
      eye). The 90% and 81% improvement in soma and axon survival, respectively,
      observed in the wild-type mice treated with RHP (both p<0.05 versus the glaucoma
      eye in the untreated mice) was still observed to a near identical extent in the
      RHP-treated HIF-1alpha RGC-KO mice. RHP had no effect on the magnitude of
      intraocular pressure elevation in either the KO or wild-type groups, indicating
      that protection was realized in both genotypes in the face of ongoing intraocular
      hypertension. CONCLUSIONS: These findings indicate that the robust, glaucomatous
      protection of the RGC soma and axons induced by RHP does not require HIF-1alpha
      mediated transcription of survival genes and other adaptive responses within the
      RGCs themselves. Rather, we infer that RGC survival is augmented secondary to the
      activation of other hypoxia-sensitive transcription factors in RGCs and/or the
      action of diffusible HIF-1alpha target gene proteins released from neighboring
      retinal cells. Ideally, the involvement of such autocrine- and/or paracrine-based
      mechanisms would be confirmed in future studies, but distinct components of the
      integrated, pleiotropic, and multicellular basis of this endogenous epigenetic
      response may prove difficult to demonstrate experimentally, as we found in the
      present study.

PMID- 24319331
TI  - Cell-mediated contraction of vitreous explants from chicken embryo: possibility
      of screening for therapeutic agents against proliferative vitreoretinal diseases.
AB  - PURPOSE: We aimed to establish a novel screening system for identifying potential
      therapeutic agents for treating proliferative vitreoretinal diseases (PVDs). In
      this study, we focused on vitreous explants from chicken embryos and evaluated
      the usefulness of quantitatively analyzing the effects of potential candidates on
      cell-mediated vitreous contraction, which leads to blindness in PVDs. METHODS:
      Vitreous explants were extracted from 19-day-old embryonic chickens and then
      incubated with retinal Muller cells or endothelial cells to permit cell adhesion.
      After cell adhesion occurred, we examined the effect of the attached cells on the
      wet weight of vitreous explants as an index of vitreous contraction. We also
      performed hematoxylin and eosin staining to characterize the cell morphology on
      the vitreous surface. RESULTS: Contraction of the vitreous explants was observed
      after cell adhesion of not only retinal Muller cells but also endothelial cells.
      We confirmed the adhesion of these cells on vitreous explants and estimated the
      number of adherent cells with 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) analysis. The cells on the vitreous surface
      presented an elongated fibroblast-like phenotype. Integrin was found to be a
      receptor involved in cell adhesion on the vitreous surface. DISCUSSION: Our
      results suggest that vitreous explants from chicken embryos may be novel useful
      tools for screening antiadhesion therapeutic agents in PVDs. This preliminary
      study must be validated with human vitreous and human retinal pigment epithelial
      cells.

PMID- 24319332
TI  - Resveratrol inhibits proliferation of hypoxic choroidal vascular endothelial
      cells.
AB  - PURPOSE: Resveratrol, a polyphenolic phytoalexin present in red wine, has a
      protective role against tumor-induced angiogenesis. Exudative age-related macular
      degeneration is characterized by hypoxia-induced choroidal vascular endothelial
      cell (CVEC) proliferation. In this study, we evaluated the effect of resveratrol
      on hypoxic CVECs and the underlying signaling pathways involved. METHODS: CVECs
      (RF/6A) after induction of hypoxia with cobalt chloride (CoCl2, 200 MUM) were
      exposed to increasing doses of resveratrol (2, 4, 6, 8, 10, and 12 MUg/ml). Cell
      viability was measured with 4-[3-(4Iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]
      1, 3-benzene disulfonate (WST-1) colorimetric assay. The effect of resveratrol on
      hypoxia-induced vascular endothelial growth factor (VEGF) release was analyzed
      with enzyme-linked immunosorbent assay. The mechanistic pathway was further
      evaluated by analyzing phosphorylated stress-activated protein kinase/c-Jun N
      terminal kinase (SAPK/JNK) using immunoblot and cleaved caspase-3 with In-Cell
      enzyme-linked immunosorbent assay. RESULTS: Resveratrol inhibited hypoxic CVEC
      proliferation. Hypoxia-induced VEGF release (30.9+/-2.6 pg/ml) was inhibited in a
      dose-dependent fashion by 2, 4, 6, 8, 10, and 12 MUg/ml resveratrol to 12.4+/
      2.1, 11.0+/-1.9, 10.3+/-3.0, 7.5+/-1.9, 5.5+/-2.0, and 5.5+/-2.3 pg/ml,
      respectively. SAPK/JNK increased by 1.8-fold and 3.9-fold after treatment with 4
      and 12 MUg/ml resveratrol, respectively. Significant increase in caspase-3 levels
      was observed with 12 MUg/ml resveratrol. CONCLUSIONS: Our study demonstrates that
      resveratrol suppresses hypoxic CVEC proliferation through activation of the
      SAPK/JNK pathway. Resveratrol, a nutritional supplement and inhibitor of CVECs,
      may be a useful adjunct to current anti-VEGF therapy in wet age-related macular
      degeneration.

PMID- 24319333
TI  - Whole-exome sequencing identifies a novel ALMS1 mutation (p.Q2051X) in two
      Japanese brothers with Alstrom syndrome.
AB  - PURPOSE: No mutations associated with Alstrom syndrome (AS), a rare autosomal
      recessive disease, have been reported in the Japanese population. The purpose of
      this study was to investigate the genetic and clinical features of two brothers
      with AS in a consanguineous Japanese family. METHODS: Whole-exome sequencing
      analysis was performed on two brothers with AS and their unaffected parents. We
      performed a complete ophthalmic examination, including decimal best-corrected
      visual acuity, slit-lamp and funduscopic examination, visual-field and color
      vision testing, full-field electroretinography, and optical coherence tomography.
      Fasting blood tests and systemic examinations were also performed. RESULTS: A
      novel mutation (c.6151C>T in exon 8) in the Alstrom syndrome 1 (ALMS1) gene that
      causes a premature termination codon at amino acid 2051 (p.Q2051X), was
      identified in the homozygous state in the affected brothers and in the
      heterozygous state in the parents. The ophthalmologic findings for both brothers
      revealed infantile-onset severe retinal degeneration and visual impairment,
      marked macular thinning, and severe cataracts. Systemic findings showed hepatic
      dysfunction, hyperlipidemia, hypogonadism, short stature, and wide feet in both
      brothers, whereas hearing loss, renal failure, abnormal digits, history of
      developmental delay, scoliosis, hypertension, and alopecia were not observed in
      either brother. The older brother exhibited type 2 diabetic mellitus and obesity,
      whereas the younger brother had hyperinsulinemia and subclinical hypothyroidism.
      CONCLUSIONS: A novel ALMS1 mutation was identified by using whole-exome
      sequencing analysis, which is useful not only to identify a disease causing
      mutation but also to exclude other gene mutations. Although characteristic
      ophthalmologic findings and most systemic findings were similar between the
      brothers, the brothers differed slightly in terms of glucose tolerance and
      thyroid function.

PMID- 24319335
TI  - Aqueous cytokines as predictors of macular edema in non-diabetic patients
      following uncomplicated phacoemulsification cataract surgery.
AB  - PURPOSE: To ascertain whether cytokines in the aqueous humor can predict macular
      edema (ME) in non-diabetic patients following uncomplicated phacoemulsification
      cataract surgery. METHODS: Undiluted aqueous humor samples were obtained from 288
      consecutive non-diabetic patients (288 eyes; 132 men and 156 women) who underwent
      cataract surgery. Macular edema was defined as an increase in the foveal center
      point thickness (FCPT) more than 30% from the preoperative baseline using optical
      coherence tomography 4 weeks after cataract surgery. The concentrations of 27
      cytokines were measured in aqueous humor samples using the multiplex bead
      immunoassay. RESULTS: No major intraoperative complications occurred. The
      incidence of ME was 8.13% (23 patients) 4 weeks after cataract surgery. Compared
      to the ME (-) patients, the concentrations of interleukin-1beta (IL-1beta;
      p=0.016), IL-6 (p=0.013), monocyte chemotactic protein-1 (MCP-1; p=0.030), and
      vascular endothelial growth factor (VEGF; p=0.033) in the ME (+) patients were
      significantly higher. In addition, the aqueous humor levels of IL-1beta
      (r=0.376), IL-6 (r=0.418), MCP-1 (r=0.348), and VEGF (r=0.375) positively
      correlated with the postoperative FCPT. However, the aqueous humor levels of IL
      10 (p=0.017) were significantly lower in patients with ME and were negatively
      correlated with the postoperative FCPT (r=-0.424). CONCLUSIONS: IL-1beta, IL-6,
      MCP-1, VEGF, and IL-10 may be potential predictors of postoperative macular
      thickness in non-diabetic patients following uncomplicated phacoemulsification
      cataract surgery.

PMID- 24319334
TI  - Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of
      autosomal dominant retinitis pigmentosa.
AB  - PURPOSE: The purpose of this project was to determine the spectrum and frequency
      of mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) that cause
      autosomal dominant retinitis pigmentosa (adRP). METHODS: A well-characterized
      adRP cohort of 251 families was tested for mutations in the exons and intron/exon
      junctions of SNRNP200 using fluorescent dideoxy sequencing. An additional 21 adRP
      families from the eyeGENE(r) Network were tested for possible mutations.
      Bioinformatic and segregation analysis was performed on novel variants. RESULTS:
      SNRNP200 mutations were identified in seven of the families tested. Two
      previously reported mutations, p.Arg681Cys and p.Ser1087Leu, were found in two
      families each. One family had the previously reported p.Arg681His mutation. Two
      novel SNRNP200 variants, p.Pro682Ser and p.Ala542Val, were also identified in one
      family each. Bioinformatic and segregation analyses suggested that these novel
      variants are likely to be pathogenic. Clinical examination of patients with
      SNRNP200 mutations showed a wide range of clinical symptoms and severity,
      including one instance of non-penetrance. CONCLUSIONS: Mutations in SNRNP200
      caused 1.6% of disease in our adRP cohort. Pathogenic mutations were found
      primarily in exons 16 and 25, but the novel p.Ala542Val mutation in exon 13
      suggests that variation in other genetic regions is also responsible for causing
      dominant disease. SNRNP200 mutations were associated with a wide range of
      clinical symptoms similar to those of individuals with other splice-factor gene
      mutations.

PMID- 24319336
TI  - Two novel PRP31 premessenger ribonucleic acid processing factor 31 homolog
      mutations including a complex insertion-deletion identified in Chinese families
      with retinitis pigmentosa.
AB  - OBJECTIVE: To identify the causative mutations in two Chinese families with
      retinitis pigmentosa (RP), and to describe the associated phenotype. METHODS:
      Individuals from two unrelated families underwent full ophthalmic examinations.
      After informed consent was obtained, genomic DNA was extracted from the venous
      blood of all participants. Linkage analysis was performed on the known genetic
      loci for autosomal dominant retinitis pigmentosa with a panel of polymorphic
      markers in the two families, and then all coding exons of the PRP31 premessenger
      ribonucleic acid processing factor 31 homolog (PRPF31) gene were screened for
      mutations with direct sequencing of PCR-amplified DNA fragments. Allele-specific
      PCR was used to validate a substitution in all available family members and 100
      normal controls. A large deletion was detected with real-time quantitative PCR
      (RQ-PCR) using a panel of primers from regions around the PRPF31 gene. Long-range
      PCR, followed by DNA sequencing, was used to define the breakpoints. RESULTS:
      Clinical examination and pedigree analysis revealed two four-generation families
      (RP24 and RP106) with autosomal dominant retinitis pigmentosa. A significant two
      point linkage odd disequilibrium score was generated at marker D19S926
      (Zmax=3.55, theta=0) for family RP24 and D19S571 (Zmax=3.21, theta=0) for family
      RP106, and further linkage and haplotype studies confined the disease locus to
      chromosome 19q13.42 where the PRPF31 gene is located. Mutation screening of the
      PRPF31 gene revealed a novel deletion c.1215delG (p.G405fs+7X) in family RP106.
      The deletion cosegregated with the family's disease phenotype, but was not found
      in 100 normal controls. No disease-causing mutation was detected in family RP24
      with PCR-based sequencing analysis. RQ-PCR and long-range PCR analysis revealed a
      complex insertion-deletion (indel) in the patients of family RP24. The deletion
      is more than 19 kb and encompasses part of the PRPF31 gene (exons 1-3), together
      with three adjacent genes. CONCLUSIONS: Our results further confirmed that
      haploinsufficiency is the main mechanism for RP11 and that genomic arrangements
      may be prevalent in PRPF31 mutations.

PMID- 24319337
TI  - Molecular and structural analysis of genetic variations in congenital cataract.
AB  - OBJECTIVE: To determine the relative contributions of mutations in congenital
      cataract cases in an Indian population by systematic screening of genes
      associated with cataract. METHODS: We enrolled 100 congenital cataract cases
      presenting at the Dr. R. P. Centre for Ophthalmic Sciences, a tertiary research
      and referral hospital (AIIMS, New Delhi, India). Crystallin, alpha A (CRYAA),
      CRYAB, CRYGs, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, beaded filament structural
      protein 1 (BFSP1), gap function protein, alpha 3 (GJA3), GJA8, and heat shock
      transcription factor 4 gene genes were amplified. Protein structure differences
      analysis was performed using Discovery Studio (DS) 2.0. RESULTS: The mean age of
      the patients was 17.45+/-16.51 months, and the age of onset was 1.618+/-0.7181
      months. Sequencing analysis of 14 genes identified 18 nucleotide variations.
      Fourteen variations were found in the crystallin genes, one in Cx-46 (GJA3), and
      three in BFSP1. CONCLUSIONS: Congenital cataract shows marked clinical and
      genetic heterogeneity. Five nucleotide variations (CRYBA4:p.Y67N, CRYBB1:p.D85N,
      CRYBB1:p.E75K, CRYBB1:p.E155K, and GJA3:p.M1V) were predicted to be pathogenic.
      Variants in other genes might also be involved in maintaining lens development,
      growth, and transparency. The study confirms that the crystallin beta cluster on
      chromosome 22, Cx-46, and BFSP1 plays a major role in maintaining lens
      transparency. This study also expands the mutation spectrum of the genes
      associated with congenital cataract.

PMID- 24319339
TI  - High Resolution Emission and Transmission Imaging Using the Same Detector.
AB  - We demonstrate the capability of one detector, the Micro-Angiographic Fluoroscope
      (MAF) detector, to image for two types of applications: nuclear medicine imaging
      and radiography. The MAF has 1024 * 1024 pixels with an effective pixel size of
      35 microns and is capable of real-time imaging at 30 fps. It has a CCD camera
      coupled by a fiber-optic taper to a light image intensifier (LII) viewing a 300
      micron thick CsI phosphor. The large variable gain of the LII provides quantum
      limited operation with little additive instrumentation noise and enables
      operation in both energy-integrating (EI) and sensitive low-exposure single
      photon counting (SPC) modes. We used the EI mode to take a radiograph, and the
      SPC mode to image a custom phantom filled with 1 mCi of I-125. The phantom is
      made of hot rods with diameters ranging from 0.9 mm to 2.3 mm. A 1 mm diameter
      parallel hole, medium energy gamma camera collimator was placed between the
      phantom and the MAF and was moved multiple times at equal intervals in random
      directions to eliminate the grid pattern corresponding to the collimator septa.
      Data was acquired at 20 fps. Two algorithms to localize the events were used: 1)
      simple threshold and 2) a weighted centroid method. Although all the hot rods
      could be clearly identified, the image generated with the simple threshold method
      shows more blurring than that with the weighted centroid method. With the diffuse
      cluster of pixels from each single detection event localized to a single pixel,
      the weighted centroid method shows improved spatial resolution. A radiograph of
      the phantom was taken with the same MAF in EI mode without the collimator. It
      shows clear structural details of the rods. Compared to the radiograph, the
      sharpness of the emission image is limited by the collimator resolution and could
      be improved by optimized collimator design. This study demonstrated that the same
      MAF detector can be used in both radioisotope and x-ray imaging, combining the
      benefits of each.

PMID- 24319338
TI  - Lenticular mitoprotection. Part B: GSK-3beta and regulation of mitochondrial
      permeability transition for lens epithelial cells in atmospheric oxygen.
AB  - PURPOSE: Loss of integrity of either the inner or outer mitochondrial membrane
      results in the dissipation of the mitochondrial electrochemical gradient that
      leads to mitochondrial membrane permeability transition (mMPT). This study
      emphasizes the role of glycogen synthase kinase 3beta (GSK-3beta) in maintaining
      mitochondrial membrane potential, thus preventing mitochondrial depolarization
      (hereafter termed mitoprotection). Using 3-(2,4-dichlorophenyl)-4-(1-methyl-1H
      indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), an inhibitor of GSK-3beta, and
      drawing a distinction between it and 1,4-diamino-2,3-dicyano-1,4-bis[2
      aminophenylthio] butadiene (UO126), an inhibitor of extracellular-signal
      regulated kinase (ERK) phosphorylation, the means by which GSK-3beta influences
      mitoprotection in cultured human lens epithelial (HLE-B3) cells and normal,
      secondary cultures of bovine lens epithelial cells, maintained in atmospheric
      oxygen, was investigated. METHODS: Virally transfected human lens epithelial
      cells (HLE-B3) and normal cultures of bovine lens epithelial cells were exposed
      to acute hypoxic conditions (about 1% O2) followed by exposure to atmospheric
      oxygen (about 21% O2). Specific antisera and western blot analysis was used to
      examine the state of phosphorylation of ERK and GSK-3beta, as well as the
      phosphorylation of a downstream substrate of GSK-3beta, glycogen synthase (GS,
      useful in monitoring GSK-3beta activity). The potentiometric dye, 1H
      benzimidazolium-5,6-dichloro-2-[3-(5,6-dichloro-1,3-diethyl-1,3-dihydro-2H
      benzimidazol-2-ylidene)-1-propenyl]-1,3-diethyl-iodide (JC-1), was used to
      monitor mitochondrial depolarization upon exposure of inhibitor treatment
      relative to the control cells (mock inhibition) in atmospheric oxygen. Caspase-3
      activation was scrutinized to determine whether mitochondrial depolarization
      inevitably leads to apoptosis. RESULTS: Treatment of HLE-B3 cells with SB216763
      (12 uM) inactivated GSK-3beta activity as verified by the enzyme's inability to
      phosphorylate its substrate, GS. SB216763-treated cells were not depolarized
      relative to the control cells as demonstrated with JC-1 fluorescent dye analysis.
      The HLE-B3 cells treated with UO126, which similarly blocked phosphorylation of
      GS, were nevertheless prone to mMPT relative to the control cells. Western blot
      analysis determined that Bcl-2-associated X (BAX) levels were unchanged for
      SB216763-treated or UO126-treated HLE-B3 cells when compared to their respective
      control cells. However, unlike the SB216763-treated cells, the UO126-treated
      cells showed a marked absence of Bcl-2, as well as phosphorylated Bcl-2 relative
      to the controls. UO126 treatment of bovine lens epithelial cells showed similar
      results with pBcl-2 levels, while the Bcl-2 content appeared unchanged relative
      to the control cells. HLE-B3 and normal bovine lens cell cultures showed
      susceptibility to mMPT associated with the loss of pBcl-2 by UO126 treatment.
      CONCLUSIONS: MITOCHONDRIAL DEPOLARIZATION MAY OCCUR BY ONE OF TWO KEY
      OCCURRENCES: interruption of the electrochemical gradient across the inner
      mitochondrial membrane resulting in mMPT or by disruption of the integrity of the
      inner or outer mitochondrial membrane. The latter scenario is generally tightly
      regulated by members of the Bcl-2 family of proteins. Inhibition of GSK-3beta
      activity by SB216763 blocks mMPT by preventing the opening of the mitochondrial
      permeability transition pore. UO126, likewise, inhibits GSK-3beta activity, but
      unlike SB216763, inhibition of ERK phosphorylation induces the loss of
      intracellular pBcl-2 levels under conditions where intracellular BAX levels
      remain constant. These results suggest that the lenticular mitoprotection
      normally afforded by the inactivation of GSK-3beta activity may, however, be
      bypassed by a loss of pBcl-2, an anti-apoptotic member of the Bcl-2 family. Bcl-2
      prevents the translocation of BAX to the mitochondrial outer membrane inhibiting
      depolarization by disrupting the normal electrochemical gradient leading to mMPT.

PMID- 24319340
TI  - Impact of aldosterone-producing adenoma on cardiac structures in
      echocardiography.
AB  - BACKGROUND: Primary aldosteronism (PA) is a most common cause of secondary
      hypertension. In PA, left ventricular hypertrophy (LVH) is more progressive than
      in any other cause of hypertension. Aldosterone-producing adenoma (APA) and
      idiopathic hyperaldosteronism (IHA) are major subtypes of PA. However there is
      little information concerned with differences of cardiac structures between these
      two subtypes. METHODS: We reviewed echocardiographic findings in 46 patients with
      PA. All patients had a positive screen test and subtypes of PA were confirmed by
      adrenal vein sampling. Subjects consisted of 20 patients with APA (APA group,
      52.4 +/- 10.8 years) and 26 patients with IHA (IHA group, 56.2 +/- 9.5 years). We
      investigated differences of cardiac structures and functions in the left atrium
      and ventricle between the APA group and IHA group. RESULTS: In terms of clinical
      characteristics, the height and duration of hypertension were greater and serum
      potassium concentration and BMI were lower in the APA group than in the IHA
      group. Plasma aldosterone concentration (PAC) and PAC to plasma renin activity
      ratio were higher in the APA group than in the IHA group. In echocardiographic
      assessment, the left atrial volume, left ventricular end-diastolic and end
      systolic diameters, left ventricular mass (LVM), and prevalence of LVH were
      greater in the APA group than in the IHA group. Multiple linear regression
      analysis revealed that the diagnosis of APA independently correlated with left
      atrial volume, left ventricular end-diastolic diameter, and LVM. CONCLUSIONS: We
      demonstrated that differences of cardiac structures between the APA group and IHA
      group existed. In APA, left atrial enlargement and LVH were more prominent than
      in IHA.

PMID- 24319341
TI  - Regional wall motion abnormality at the lateral wall disturbs correlations
      between tissue Doppler E/e' ratios and left ventricular diastolic performance
      parameters measured by invasive methods.
AB  - BACKGROUND: The impact of regional wall motion abnormality (RWMA) on the accuracy
      of heart failure with preserved ejection fraction (HFpEF) diagnosis using the
      E/e' ratio, which is a non-invasive parameter of left ventricular diastolic
      performance, is unknown. The purpose of this study was to elucidate the impact of
      RWMA of the lateral wall (RWMAlat) on the correlation between E/e' and invasive
      parameters of left ventricular diastolic performance. METHODS: Three hundred and
      eight consecutive patients undergoing tissue Doppler imaging and catheterization
      pressure examination were retrospectively analyzed. E/e' was calculated as the
      ratio of early diastolic transmitral flow velocity to mitral annular velocity at
      the lateral wall. Invasive parameters including left ventricular end-diastolic
      pressure (LVEDP) and isovolumetric relaxation time constant (tau) were assessed
      based on the left ventricular pressure study. Correlation coefficients between
      E/e' and these invasive parameters were analyzed and compared between cases with
      RWMAlat and without RWMA. RESULTS: LVEDP and tau correlated well with E/e' for
      all 308 patients (r = 0.51 and r = 0.65, respectively). Sixty-two patients had
      RWMA; the remaining 246 did not have RWMAlat. We confirmed that the presence of
      RWMAlat weakens both the correlations between E/e' and LVEDP (r = 0.574 vs. r =
      0.381), and E/e' and tau (r = 0.729 vs. r = 0.461). CONCLUSIONS: Although E/e'
      correlates well with parameters of left ventricular diastolic performance
      assessed by invasive methods, the presence of RWMAlat worsens this correlation.
      In cases with RWMAlat, careful assessment is required for HFpEF diagnosis because
      the diagnostic value of the E/e' ratio could be decreased compared to patients
      without RWMAlat.

PMID- 24319342
TI  - Enhanced Facial Symmetry Assessment in Orthodontists.
AB  - Assessing facial symmetry is an evolutionarily important process, which suggests
      that individual differences in this ability should exist. As existing data are
      inconclusive, the current study explored whether a group trained in facial
      symmetry assessment, orthodontists, possessed enhanced abilities. Symmetry
      assessment was measured using face and non-face stimuli among orthodontic
      residents and two control groups: university participants with no symmetry
      training and airport security luggage screeners, a group previously shown to
      possess expert visual search skills unrelated to facial symmetry. Orthodontic
      residents were more accurate at assessing symmetry in both upright and inverted
      faces compared to both control groups, but not for non-face stimuli. These
      differences are not likely due to motivational biases or a speed-accuracy
      tradeoff-orthodontic residents were slower than the university participants but
      not the security screeners. Understanding such individual differences in facial
      symmetry assessment may inform the perception of facial attractiveness.

PMID- 24319343
TI  - Ethical, Legal and Social Issues Surrounding Research on Genetic Contributions to
      Anti-Social Behavior.
AB  - Scientific study of genetic contributions to chronic antisocial behavior has
      stemmed from many lines of research in recent years. Genetic research involving
      twin, family, and adoption studies have traditionally been used to compare the
      health and behavior outcomes of individuals who share the same environment or
      hereditary lineage; several of these studies have concluded that heredity plays
      some role in the formation of chronic antisocial behavior, including various
      forms of aggression and chronic norm-defiance. However, the ethical, social, and
      legal environment surrounding research on the biological contributions to
      antisocial behavior in the United States is contentious. Although there has been
      some discussion in the last few decades regarding the ethical, social, and legal
      concerns around this type of research within academic and policy circles,
      analysis and discussion of these concerns rarely appear together. This paper
      explores the main themes that interact to form the basis of much of the
      resistance to positing biological contributions to antisocial behavior.

PMID- 24319344
TI  - Social status and the pursuit of positive social identity: Systematic domains of
      intergroup differentiation and discrimination for high- and low- status groups.
AB  - Research on intergroup discrimination has focused on the cognitive and
      motivational mechanisms involved, but the role of stereotype content has been
      neglected. Drawing on social identity theory and stereotype content research, the
      current studies investigated the role of stereotype content in intergroup
      differentiation and discrimination. Across two studies, students from high- and
      low-status groups differentiated themselves positively on stereotypes of
      competence and warmth respectively, and in allocations of resources in domains
      relevant to competence (academics, research) and warmth (sports, community
      outreach). Furthermore, there was evidence that discrimination by high- and low
      status groups was driven by their respective stereotypes of competence and
      warmth. It is argued that stereotypes of competence and warmth, derived from
      status and power relations between groups, define the domains in which groups
      pursue positively distinct identities.

PMID- 24319345
TI  - O-6-methylguanine-deoxyribonucleic acid methyltransferase methylation enhances
      response to temozolomide treatment in esophageal cancer.
AB  - BACKGROUND: World-wide, esophageal cancer is a growing epidemic and patients
      frequently present with advanced disease that is surgically inoperable. Hence,
      chemotherapy is the predominate treatment. Cytotoxic platinum compounds are
      mostly used, but their efficacy is only moderate. Newer alkylating agents have
      shown promise in other tumor types, but little is known about their utility in
      esophageal cancer. METHODS: We utilized archived human esophageal cancer samples
      and esophageal cancer cell lines to evaluate O-6-methylguanine-deoxyribonucleic
      acid methyltransferase (MGMT) hypermethylation status and determined sensitivity
      to the alkylating drug temozolomide (TMZ). Immunoblot analysis was performed to
      determine MGMT protein expression in cell lines. To assess and confirm the effect
      of TMZ treatment in a methylated esophageal cancer cell line in vivo, a mouse
      flank xenograft tumor model was utilized. RESULTS: Nearly 71% (12/17) of
      adenocarcinoma and 38% (3/8) of squamous cell carcinoma (SCC) patient samples
      were MGMT hypermethylated. Out of four adenocarcinoma and nine SCC cell lines
      tested, one of each histology was hypermethylated. Immunoblot analyses confirmed
      that hypermethylated cell lines did not express the MGMT protein. In vitro cell
      viability assays showed the methylated Kyse-140 and FLO cells to be sensitive to
      TMZ at an IC50 of 52-420 MUM, whereas unmethylated cells Kyse-410 and SKGT-4 did
      not respond. In an in vivo xenograft tumor model with Kyse-140 cells, which are
      MGMT hypermethylated, TMZ treatment abrogated tumor growth by more than 60%.
      CONCLUSION: MGMT methylation may be an important biomarker in subsets of
      esophageal cancers and targeting by TMZ may be utilized to successfully treat
      these patients.

PMID- 24319346
TI  - Measuring Time Use of Older Couples: Lessons from the Panel Study of Income
      Dynamics.
AB  - Time diaries are a well established method for providing population estimates of
      the amount of time and types of activities respondents carry out over the course
      of a full day. This paper focuses on a computer assisted telephone application
      developed to collect multiple, same-day 24-hour diaries from older couples who
      participated in the 2009 Panel Study of Income Dynamics (PSID). We present
      selected findings from developmental and field activities, highlighting methods
      for three diary enhancements: 1) implementation of a multiple, same-day diary
      design; 2) minimizing erroneous reporting of sequential activities as
      simultaneous; and 3) tailoring activity descriptors (or "follow-up" questions)
      that depend on a pre-coded activity value. A final section discusses limitations
      and implications for future time diary efforts.

PMID- 24319347
TI  - Child Maltreatment and Adult Substance Abuse: The Role of Memory.
AB  - Child maltreatment is a risk factor for substance abuse in adulthood. This study
      examines whether memory of maltreatment is a necessary link in the path leading
      from prospectively measured childhood maltreatment to adult substance use
      problems. Official Child Protective Services reports and adult retrospective
      recall of childhood maltreatment were used to predict illegal drug use and
      alcohol problems in adulthood controlling for covariates. Memory was a necessary
      link in the path between prospective reports of maltreatment and alcohol
      problems, and an important link in the path between prospective reports and
      illegal drug use. Implications for prevention and treatment are discussed.

PMID- 24319348
TI  - A comparison of averaged and full models to study the third-body perturbation.
AB  - The effects of a third-body travelling in a circular orbit around a main body on
      a massless satellite that is orbiting the same main body are studied under two
      averaged models, single and double, where expansions of the disturbing function
      are made, and the full restricted circular three-body problem. The goal is to
      compare the behavior of these two averaged models against the full problem for
      long-term effects, in order to have some knowledge of their differences. The
      single averaged model eliminates the terms due to the short period of the
      spacecraft. The double average is taken over the mean motion of the satellite and
      the mean motion of the disturbing body, so removing both short period terms. As
      an example of the methods, an artificial satellite around the Earth perturbed by
      the Moon is used. A detailed study of the effects of different initial conditions
      in the orbit of the spacecraft is made. 

PMID- 24319349
TI  - Fuzzy diagnostic system for oleo-pneumatic drive mechanism of high-voltage
      circuit breakers.
AB  - Many oil-based high-voltage circuit breakers are still in use in national power
      networks of developing countries, like those in Eastern Europe. Changing these
      breakers with new more reliable ones is not an easy task, due to their
      implementing costs. The acting device, called oleo-pneumatic mechanism (MOP),
      presents the highest fault rate from all components of circuit breaker.
      Therefore, online predictive diagnosis and early detection of the MOP fault
      tendencies are very important for their good functioning state. In this paper,
      fuzzy logic approach is used for the diagnosis of MOP-type drive mechanisms.
      Expert rules are generated to estimate the MOP functioning state, and a fuzzy
      system is proposed for predictive diagnosis. The fuzzy inputs give information
      about the number of starts and time of functioning per hour, in terms of short
      term components, and their mean values. Several fuzzy systems were generated,
      using different sets of membership functions and rule bases, and their output
      performances are studied. Simulation results are presented based on an input data
      set, which contains hourly records of operating points for a time horizon of five
      years. The fuzzy systems work well, making an early detection of the MOP fault
      tendencies. 

PMID- 24319350
TI  - Anatomy and surgical relevance of Rouviere's sulcus.
AB  - Rouviere's sulcus (RS) (i.e., incisura hepatis dextra, Gans incisura) represents
      an important anatomical landmark. The aim of the study was to determine the
      frequency of the RS, its description, its location, its relations to the right
      portal pedicle and to the plane of the common bile duct, and the evaluation of
      the surgical relevance of the obtained data. Forty macroscopically healthy and
      undamaged livers were removed during autopsies from cadavers of both sexes. The
      RS was present in 82% of the cases and in these the open RS was identified in 70%
      of the livers. The fused type was observed in 12% of the cases; 18% of the livers
      had no sulcus. The mean length of the open type RS was 28 +/- 2 mm (range 24-32
      mm) and its mean depth was 6 +/- 2 mm (range 4-8 mm). The right posterior
      sectional pedicle was found in the RS in 70% of the cases. In 5% of the livers,
      we also dissected a branch of the anterior sectional pedicle. Inside 25% of the
      RS, we found the vein of segment 6. The RS identification may avoid bile duct
      injury during laparoscopic cholecystectomy and enables elective vascular control
      during the right liver resection. 

PMID- 24319352
TI  - Monodispersed ZnO nanoparticles and their use in heterojunction solar cell.
AB  - Monodispersed ZnO nanoparticles have been synthesised in ethylene glycol medium
      using zinc acetate and sodium hydroxide at room temperature through ultrasonic
      treatment. The monodispersed ZnO nanoparticles were characterized by XRD, TEM,
      SEM, and optical spectroscopy. The results indicate that ZnO shows the hexagonal
      wurtzite structure having 8 nm average particle size with the band gap of 3.93
      eV. ZnO nanoparticles blended with P3HT show the improvement in the interchains
      and intrachains ordering as compared to pure P3HT. The power conversion
      efficiency of P3HT/ZnO solar cell is found to be 0.88%, which is comparable with
      the result obtained by other researchers. 

PMID- 24319351
TI  - An update on diabetic women obstetrical outcomes linked to preconception and
      pregnancy glycemic profile: a systematic literature review.
AB  - Women with type 2 diabetes were less likely to have diabetes related
      complications than women with type 1. Women with type 1 diabetes had a high
      prepregnancy care and showed a worse glycemic control than women with type 2 both
      in the preconception period and during pregnancy. Obstetrical outcomes showed
      that preeclampsia and stillbirth rate is almost doubled in type 1 patients while
      perinatal deaths and SGA importantly increased in type 2 diabetes. In modern
      obstetrical care it is mandatory to maintain glucose levels as close to normal as
      possible particularly in diabetic population. HbA1C no higher than 6% before
      pregnancy and during the first trimester seems to decrease the risk of adverse
      obstetrical outcomes. Both the preconceptional counseling and glycemic profile
      optimization represent a fundamental step to improve pregnancy outcomes in women
      with preexisting diabetes. A systematic approach to family planning and the
      availability of preconception care for all diabetic women who desire pregnancy
      could be an essential step for diabetic management program. 

PMID- 24319353
TI  - Compost and crude humic substances produced from selected wastes and their
      effects on Zea mays L. nutrient uptake and growth.
AB  - Production of agriculture and timber commodities leads generation of enormous
      quantity of wastes. Improper disposal of these agroindustrial wastes pollutes the
      environment. This problem could be reduced by adding value to them. Therefore, a
      study was carried out to analyse and compare the nutrients content of RS, RH, SD,
      and EFB of composts and crude humic substances; furthermore, their effect on
      growth, dry matter production, and nutrient uptake for Zea mays L., and selected
      soil chemical properties were evaluated. Standard procedures were used to analyze
      humic acids (HA), crude fulvic acids (CFA), crude humin (CH), soil, dry matter
      production and nutrient uptake. Sawdust and RS compost matured at 42 and 47 days,
      respectively, while RH and EFB composts were less matured at 49th day of
      composting. Rice straw compost had higher ash, N, P, CEC, HA, K, and Fe contents
      with lower organic matter, total organic carbon, and C/N and C/P ratios. The HA
      of sawdust compost showed higher carbon, carboxylic, K, and Ca contents compared
      to those of RS, RH, and EFB. Crude FA of RS compost showed highest pH, total K,
      Ca, Mg, and Na contents. Crude humin from RS compost had higher contents of ash,
      N, P, and CEC. Rice straw was superior in compost, CFA, and CH, while sawdust
      compost was superior in HA. Application of sawdust compost significantly
      increased maize plants' diameter, height, dry matter production, N, P, and
      cations uptake. It also reduced N, P, and K based chemical fertilizer use by 90%.
      Application of CH and the composts evaluated in this study could be used as an
      alternative for chemical fertilizers in maize cultivation. 

PMID- 24319354
TI  - Comparison of predictive control methods for high consumption industrial furnace.
AB  - We describe several predictive control approaches for high consumption industrial
      furnace control. These furnaces are major consumers in production industries, and
      reducing their fuel consumption and optimizing the quality of the products is one
      of the most important engineer tasks. In order to demonstrate the benefits from
      implementation of the advanced predictive control algorithms, we have compared
      several major criteria for furnace control. On the basis of the analysis, some
      important conclusions have been drawn. 

PMID- 24319355
TI  - Studies of the interaction between isoimperatorin and human serum albumin by
      multispectroscopic method: identification of possible binding site of the
      compound using esterase activity of the protein.
AB  - Isoimperatorin is one of the main components of Prangos ferulacea as a linear
      furanocoumarin and used as anti-inflammatory, analgesic, antispasmodic, and
      anticancer drug. Human serum albumin (HSA) is a principal extracellular protein
      with a high concentration in blood plasma and carrier for many drugs to different
      molecular targets. Since the carrying of drug by HSA may affect on its structure
      and action, we decided to investigate the interaction between HSA and
      isoimperatorin using fluorescence and UV spectroscopy. Fluorescence data
      indicated that isoimperatorin quenches the intrinsic fluorescence of the HSA via
      a static mechanism and hydrophobic interaction play the major role in the drug
      binding. The binding average distance between isoimperatorin and Trp 214 of HSA
      was estimated on the basis of the theory of Forster energy transfer. Decrease of
      protein surface hydrophobicity (PSH) was also documented upon isoimperatorin
      binding. Furthermore, the synchronous fluorescence spectra show that the
      microenvironment of the tryptophan residues does not have obvious changes. Site
      marker compettive and fluorescence experiments revealed that the binding of
      isoimperatorin to HSA occurred at or near site I. Finally, the binding details
      between isoimperatorin and HSA were further confirmed by molecular docking and
      esterase activity inhibition studies which revealed that drug was bound at
      subdomain IIA. 

PMID- 24319356
TI  - Antioxidant, antityrosinase, anticholinesterase, and nitric oxide inhibition
      activities of three malaysian macaranga species.
AB  - The methanol extracts of three Macaranga species (M. denticulata, M. pruinosa,
      and M. gigantea) were screened to evaluate their total phenolic contents and
      activities as cholinesterase inhibitors, nitric oxide (NO) production inhibitors,
      tyrosinase inhibitors, and antioxidants. The bark of M. denticulata showed the
      highest total phenolic content (2682 mg gallic acid equivalent (GAE)/100 g) and
      free radical scavenging activity (IC50 = 0.063 mg/mL). All of the samples
      inhibited linoleic acid peroxidation by greater than 80%, with the leaves of M.
      gigantea exhibiting the highest inhibition of 92.21%. Most of the samples
      exhibited significant antioxidant potential. The bark of M. denticulata and the
      leaves of both M. pruinosa and M. gigantea exhibited greater than 50% tyrosinase
      inhibition, with the bark of M. denticulata having the highest percentage of
      inhibition (68.7%). The bark and leaves of M. denticulata exhibited greater than
      50% inhibition (73.82% and 54.50%, resp.) of the acetylcholinesterase enzyme
      (AChE), while none of the samples showed any significant inhibition of
      butyrylcholinesterase (BChE). Only the bark of M. denticulata and M. gigantea
      displayed greater than 50% inhibition of nitric oxide production in cells (81.79%
      and 56.51%, resp.). These bioactivities indicate that some Macaranga spp. have
      therapeutic potential in medicinal research. 

PMID- 24319358
TI  - Infrared thermography in the architectural field.
AB  - Infrared thermography is becoming ever more popular in civil
      engineering/architecture mainly due to its noncontact character which includes
      two great advantages. On one side, it prevents the object, under inspection, from
      any alteration and this is worthwhile especially in the presence of precious
      works of art. On the other side, the personnel operate in a remote manner far
      away from any hazard and this complies well with safety at work regulations. What
      is more, it offers the possibility to quickly inspect large surfaces such as the
      entire facade of a building. This paper would be an overview of the use of
      infrared thermography in the architectural and civil engineering field. First,
      some basic testing procedures are described, and then some key examples are
      presented owing to both laboratory tests and applications in situ spanning from
      civil habitations to works of art and archaeological sites. 

PMID- 24319357
TI  - Engineering rhizobial bioinoculants: a strategy to improve iron nutrition.
AB  - Under field conditions, inoculated rhizobial strains are at a survival
      disadvantage as compared to indigenous strains. In order to out-compete native
      rhizobia it is not only important to develop strong nodulation efficiency but
      also increase their competence in the soil and rhizosphere. Competitive survival
      of the inoculated strain may be improved by employing strain selection and by
      genetic engineering of superior nitrogen fixing strains. Iron sufficiency is an
      important factor determining the survival and nodulation by rhizobia in soil.
      Siderophores, a class of ferric specific ligands that are involved in receptor
      specific iron transport into bacteria, constitute an important part of iron
      acquisition systems in rhizobia and have been shown to play a role in symbiosis
      as well as in saprophytic survival. Soils predominantly have iron bound to
      hydroxamate siderophores, a pool that is largely unavailable to catecholate
      utilizing rhizobia. Outer membrane receptors for uptake of ferric hydroxamates
      include FhuA and FegA which are specific for ferrichrome siderophore. Increase in
      nodule occupancy and enhanced plant growth of the fegA and fhuA expressing
      engineered bioinoculants rhizobial strain have been reported. Engineering
      rhizobia for developing effective bioinoculants with improved ability to utilize
      heterologous siderophores could provide them with better iron acquisition ability
      and consequently, rhizospheric stability. 

PMID- 24319359
TI  - Value of diffusion-weighted MR imaging for the detection of nephritis.
AB  - PURPOSE: To evaluate diffusion-weighted MR imaging (DWI-MRI) for the detection
      and assessment of infectious renal disease. MATERIALS AND METHODS: Twenty-one
      patients with suspicious increased signal intensity of the kidneys on DWI
      sequences and corresponding ADC decrease were identified. Sixty patients without
      clinical signs of renal infection served as a control group. All patients were
      examined with the following sequences: EPI-DWI (0/400/800 s/mm(2)), T2w HASTE,
      and T1w VIBE after intravenous injection of Gd-chelate. Confirmation of renal
      infection was established on the basis of clinical criteria. T1w and T2w images
      were assessed and compared to DWI for the presence of altered signal, and the
      degree of the visibility of pathology was graded on an ordinal three-point scale.
      RESULTS: In all 21 patients with positive DWI findings a renal infection could be
      confirmed. T2w imaging and contrast-enhanced T1w imaging displayed obvious
      pathologic signal in 3/21 (14%) and 11/19 (58%) patients and slightly pathologic
      signal in 17/21 (81%) and 7/19 (37%), respectively. The median visibility score
      of 2 for the DWI and the T1w images was significantly higher than the score of 1
      for the T2w imaging, P = 0.0001 (DWI versus T2w) and P = 0.078 (T1w versus T2w).
      CONCLUSION: DWI of the kidneys seems to be highly sensitive for the detection of
      infections within the kidney.

PMID- 24319360
TI  - Bending response of cross-ply laminated composite plates with diagonally
      perturbed localized interfacial degeneration.
AB  - A laminated composite plate element with an interface description is developed
      using the finite element approach to investigate the bending performance of two
      layer cross-ply laminated composite plates in presence of a diagonally perturbed
      localized interfacial degeneration between laminae. The stiffness of the laminate
      is expressed through the assembly of the stiffnesses of lamina sub-elements and
      interface element, the latter of which is formulated adopting the well-defined
      virtually zero-thickness concept. To account for the extent of both shear and
      axial weak bonding, a degeneration ratio is introduced in the interface
      formulation. The model has the advantage of simulating a localized weak bonding
      at arbitrary locations, with various degeneration areas and intensities, under
      the influence of numerous boundary conditions since the interfacial description
      is expressed discretely. Numerical results show that the bending behavior of
      laminate is significantly affected by the aforementioned parameters, the greatest
      effect of which is experienced by those with a localized total interface
      degeneration, representing the case of local delamination. 

PMID- 24319361
TI  - Multi-objective approach for energy-aware workflow scheduling in cloud computing
      environments.
AB  - We address the problem of scheduling workflow applications on heterogeneous
      computing systems like cloud computing infrastructures. In general, the cloud
      workflow scheduling is a complex optimization problem which requires considering
      different criteria so as to meet a large number of QoS (Quality of Service)
      requirements. Traditional research in workflow scheduling mainly focuses on the
      optimization constrained by time or cost without paying attention to energy
      consumption. The main contribution of this study is to propose a new approach for
      multi-objective workflow scheduling in clouds, and present the hybrid PSO
      algorithm to optimize the scheduling performance. Our method is based on the
      Dynamic Voltage and Frequency Scaling (DVFS) technique to minimize energy
      consumption. This technique allows processors to operate in different voltage
      supply levels by sacrificing clock frequencies. This multiple voltage involves a
      compromise between the quality of schedules and energy. Simulation results on
      synthetic and real-world scientific applications highlight the robust performance
      of the proposed approach. 

PMID- 24319362
TI  - Locally expansive solutions for a class of iterative equations.
AB  - Iterative equations which can be expressed by the following form f (n) (x) = H(x,
      f(x), f (2)(x),..., f (n-1)(x)), where n >= 2, are investigated. Conditions for
      the existence of locally expansive C (1) solutions for such equations are given. 

PMID- 24319363
TI  - Effects of PARP-1 deficiency on Th1 and Th2 cell differentiation.
AB  - T cell differentiation to effector Th cells such as Th1 and Th2 requires the
      integration of multiple synergic and antagonist signals. Poly(ADP-ribosy)lation
      is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose)
      polymerases (PARPs). Recently, many reports showed that PARP-1, the prototypical
      member of the PARP family, plays a role in immune/inflammatory responses.
      Consistently, its enzymatic inhibition confers protection in several models of
      immune-mediated diseases, mainly through an inhibitory effect on NF-kappaB (and
      NFAT) activation. PARP-1 regulates cell functions in many types of immune cells,
      including dendritic cells, macrophages, and T and B lymphocytes. Our results show
      that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells.
      Under both nonskewing and Th2-polarizing conditions, naive CD4 cells from PARP
      1KO mice generated a reduced frequency of IL-4(+) cells, produced less IL-5, and
      expressed GATA-3 at lower levels compared with cells from wild type mice.
      Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1
      cells. Indeed, the frequency of IFN-gamma (+) cells as well as IFN-gamma
      production, in nonskewing and Th1-polarizing conditions, was not affected by PARP
      1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in
      Th2 cell differentiation and it might be a target to be exploited for the
      modulation of Th2-dependent immune-mediated diseases. 

PMID- 24319365
TI  - Lack of significant association between plasma/serum miR-221 expression and poor
      survival of carcinoma: a meta-analysis.
AB  - Background. MicroRNAs (miRNAs) exhibit altered expression levels in cancers, and
      they may play a potential role as diagnostic and prognostic biomarkers of
      cancers. The aim of this meta-analysis was to summarize recent advances in miR
      221 involvement in a variety of carcinomas and derive a more precise estimation
      of the relationship between circulating miR-221 level and survival of cancer
      patients. Methods. We searched online PubMed, EMBASE, and Cochrane Library up to
      August 2013 to identify relevant studies. Data were collected from studies
      comparing survival in patients with various carcinomas with higher miR-221
      expression to those with lower levels. Pooled hazard ratios (HRs) of miR-221 for
      survival were calculated. Results. There were 4 studies included in the meta
      analysis. The results of meta-analysis suggested that no significant difference
      in poor overall survival between miR-221 high and low groups (OR = 0.94, 95%, CI
      = 0.47-1.87, Z = 0.17, and P = 0.863). Conclusions. The current meta-analysis
      showed the equivalence of high and low plasma/serum miR-221 expression for
      carcinomas in terms of survival. 

PMID- 24319366
TI  - Compact ultra wide band microstrip bandpass filter based on multiple-mode
      resonator and modified complementary split ring resonator.
AB  - A new class of broadband microstrip filters for Ultra Wide Band (UWB)
      applications is proposed. In the design, different stages of parallel-coupled
      microstrip line and other stages with a Modified Complementary Split Ring
      Resonator (MCSRR)-a concept proposed here for the first time-are adjusted to
      obtain the desired response with broadband, sharp rejection, low insertion loss,
      and low return loss. Full wave simulation results as well as measurement results
      from fabricated prototypes are presented, showing good agreement. The proposed
      technique offers a new alternative to implement low-cost high-performance filter
      devices, applicable to a wide range of communication systems. 

PMID- 24319364
TI  - Emergent biomarkers of residual cardiovascular risk in patients with low HDL-c
      and/or high triglycerides and average LDL-c concentrations: focus on HDL
      subpopulations, Oxidized LDL, adiponectin, and uric acid.
AB  - This study intended to determine the impact of HDL-c and/or TGs levels on
      patients with average LDL-c concentration, focusing on lipidic, oxidative,
      inflammatory, and angiogenic profiles. Patients with cardiovascular risk factors
      (n = 169) were divided into 4 subgroups, combining normal and low HDL-c with
      normal and high TGs patients. The following data was analyzed: BP, BMI, waist
      circumference and serum glucose, Total-c, TGs, LDL-c, oxidized-LDL, total HDL-c
      and HDL subpopulations, paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF-
      alpha , adiponectin, VEGF, and iCAM1. The two populations with increased TGs
      levels, regardless of the normal or low HDL-c, presented obesity and higher waist
      circumference, Total-c, LDL-c, Ox-LDL, and uric acid. Adiponectin concentration
      was significantly lower and VEGF was higher in the population with cumulative low
      values of HDL-c and high values of TGs, while HDL quality was reduced in the
      populations with impaired values of HDL-c and/or TGs, viewed by reduced large and
      increased small HDL subfractions. In conclusion, in a population with
      cardiovascular risk factors, low HDL-c and/or high TGs concentrations seem to be
      associated with a poor cardiometabolic profile, despite average LDL-c levels.
      This condition, often called residual risk, is better evidenced by using both
      traditional and nontraditional CV biomarkers, including large and small HDL
      subfractions, Ox-LDL, adiponectin, VEGF, and uric acid. 

PMID- 24319367
TI  - A compact symmetric microstrip filter based on a rectangular meandered-line
      stepped impedance resonator with a triple-band bandstop response.
AB  - This paper presents a symmetric-type microstrip triple-band bandstop filter
      incorporating a tri-section meandered-line stepped impedance resonator (SIR). The
      length of each section of the meandered line is 0.16, 0.15, and 0.83 times the
      guided wavelength (lambda g ), so that the filter features three stop bands at
      2.59 GHz, 6.88 GHz, and 10.67 GHz, respectively. Two symmetric SIRs are employed
      with a microstrip transmission line to obtain wide bandwidths of 1.12, 1.34, and
      0.89 GHz at the corresponding stop bands. Furthermore, an equivalent circuit
      model of the proposed filter is developed, and the model matches the
      electromagnetic simulations well. The return losses of the fabricated filter are
      measured to be -29.90 dB, -28.29 dB, and -26.66 dB while the insertion losses are
      0.40 dB, 0.90 dB, and 1.10 dB at the respective stop bands. A drastic reduction
      in the size of the filter was achieved by using a simplified architecture based
      on a meandered-line SIR. 

PMID- 24319368
TI  - Relation of depression, anxiety, and quality of life with outcome after
      percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: Despite, increasing number of percutaneous transluminal coronary
      angioplasty (PTCA) being performed, there is a paucity of Indian studies on the
      psychological effects of PTCA. Aim. To study the relation of anxiety, depression,
      and health related quality of life with outcome after PTCA. METHODS: A total of
      35 patients undergoing PTCA were included in the present project with their
      informed consent. All patients filled a specially designed proforma, the Hospital
      Anxiety and Depression Scale, Coronary Scale, Seattle Angina Questionnaire, and a
      health related quality of life measure (EQ 5D) one day before undergoing PTCA.
      Three days after PTCA patients were reassessed with the Hospital anxiety &
      depression scale, Seattle angina questionnaire and the EQ 5D. RESULTS: Analysis
      showed that 46% had significant anxiety and 32.1% had significant depression
      before PTCA. Following successful PTCA, none of the patients had significant
      anxiety, and only 2 (3.6%) had significant depression. On the Seattle Angina
      Questionnaire, physical limitation reduced from 67.9 to 48. Disease perception
      improved from 21.2 to 37.1. On the EQ5D, the health status improved from 42.7
      before PTCA to 78.7 after PTCA. CONCLUSION: Successful PTCA resulted in
      significant reduction in anxiety, depression, and physical limitation and
      improvement in disease perception and health status.

PMID- 24319369
TI  - Positive periodic solutions of an epidemic model with seasonality.
AB  - An SEI autonomous model with logistic growth rate and its corresponding
      nonautonomous model are investigated. For the autonomous case, we give the
      attractive regions of equilibria and perform some numerical simulations. Basic
      demographic reproduction number R d is obtained. Moreover, only the basic
      reproduction number R 0 cannot ensure the existence of the positive equilibrium,
      which needs additional condition R d > R 1. For the nonautonomous case, by
      introducing the basic reproduction number defined by the spectral radius, we
      study the uniform persistence and extinction of the disease. The results show
      that for the periodic system the basic reproduction number is more accurate than
      the average reproduction number. 

PMID- 24319370
TI  - PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal
      mouse model after cold prolonged ischemia.
AB  - We test the hypothesis that PARP inhibition can decrease acute tubular necrosis
      (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR)
      in kidneys preserved at 4 degrees C in University of Wisconsin (UW) solution.
      Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0)
      knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4
      dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a
      concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice
      were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h
      in UW solution plus DPQ). We processed samples for morphological,
      immunohistochemical, ultrastructural, and western-blotting studies. Results.
      Prolonged cold ischemia time in UW solution increased PARP-1 expression and
      kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation
      in UW solution decreased PARP-1 nuclear expression in renal tubules and renal
      damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion.
      In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions
      in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these
      data suggest that pharmacological manipulation of PARP activity may have salutary
      effects in cold-stored organs at transplantation. 

PMID- 24319371
TI  - Transient hemodynamic changes upon changing a BCPA into a TCPC in staged Fontan
      operation: a computational model study.
AB  - The clinical benefits of the Fontan operation in treating single-ventricle
      defects have been well documented. However, perioperative mortality or morbidity
      remains a critical problem. The purpose of the present study was to identify the
      cardiovascular factors that dominate the transient hemodynamic changes upon the
      change of a bidirectional cavopulmonary (Glenn) anastomosis (BCPA) into a total
      cavopulmonary connection (TCPC). For this purpose, two computational models were
      constructed to represent, respectively, a single-ventricle circulation with a
      BCPA and that with a TCPC. A series of model-based simulations were carried out
      to quantify the perioperative hemodynamic changes under various cardiovascular
      conditions. Obtained results indicated that the presence of a low pulmonary
      vascular resistance and/or a low lower-body vascular resistance is beneficial to
      the increase in transpulmonary flow upon the BCPA to TCPC change. Moreover, it
      was found that ventricular diastolic dysfunction and mitral valve regurgitation,
      despite being well-known risk factors for poor postoperative outcomes, do not
      cause a considerable perioperative reduction in transpulmonary flow. The findings
      may help physicians to assess the perioperative risk of the TCPC surgery based on
      preoperative measurement of cardiovascular function. 

PMID- 24319372
TI  - The assessment methods of laryngeal muscle activity in muscle tension dysphonia:
      a review.
AB  - The purpose of this paper is to review the methods used for the assessment of
      muscular tension dysphonia (MTD). The MTD is a functional voice disorder
      associated with abnormal laryngeal muscle activity. Various assessment methods
      are available in the literature to evaluate the laryngeal hyperfunction. The case
      history, laryngoscopy, and palpation are clinical methods for the assessment of
      patients with MTD. Radiography and surface electromyography (EMG) are objective
      methods to provide physiological information about MTD. Recent studies show that
      surface EMG can be an effective tool for assessing muscular tension in MTD. 

PMID- 24319373
TI  - Nexfin noninvasive continuous hemodynamic monitoring: validation against
      continuous pulse contour and intermittent transpulmonary thermodilution derived
      cardiac output in critically ill patients.
AB  - INTRODUCTION: Nexfin (Bmeye, Amsterdam, Netherlands) is a noninvasive cardiac
      output (CO) monitor based on finger arterial pulse contour analysis. The aim of
      this study was to validate Nexfin CO (NexCO) against thermodilution (TDCO) and
      pulse contour CO (CCO) by PiCCO (Pulsion Medical Systems, Munich, Germany).
      PATIENTS AND METHODS: In a mix of critically ill patients (n = 45), NexCO and CCO
      were measured continuously and recorded at 2-hour intervals during the 8-hour
      study period. TDCO was measured at 0-4-8 hrs. RESULTS: NexCO showed a moderate to
      good (significant) correlation with TDCO (R (2) 0.68, P < 0.001) and CCO (R (2)
      0.71, P < 0.001). Bland and Altman analysis comparing NexCO with TDCO revealed a
      bias (+/- limits of agreement, LA) of 0.4 +/- 2.32 L/min (with 36% error) while
      analysis comparing NexCO with CCO showed a bias (+/-LA) of 0.2 +/- 2.32 L/min
      (37% error). NexCO is able to follow changes in TDCO and CCO during the same time
      interval (level of concordance 89.3% and 81%). Finally, polar plot analysis
      showed that trending capabilities were acceptable when changes in NexCO
      (DeltaNexCO) were compared to DeltaTDCO and DeltaCCO (resp., 89% and 88.9% of
      changes were within the level of 10% limits of agreement). CONCLUSION: we found a
      moderate to good correlation between CO measurements obtained with Nexfin and
      PiCCO.

PMID- 24319374
TI  - Aliphatic, cyclic, and aromatic organic acids, vitamins, and carbohydrates in
      soil: a review.
AB  - Organic acids, vitamins, and carbohydrates represent important organic compounds
      in soil. Aliphatic, cyclic, and aromatic organic acids play important roles in
      rhizosphere ecology, pedogenesis, food-web interactions, and decontamination of
      sites polluted by heavy metals and organic pollutants. Carbohydrates in soils can
      be used to estimate changes of soil organic matter due to management practices,
      whereas vitamins may play an important role in soil biological and biochemical
      processes. The aim of this work is to review current knowledge on aliphatic,
      cyclic, and aromatic organic acids, vitamins, and carbohydrates in soil and to
      identify directions for future research. Assessments of organic acids (aliphatic,
      cyclic, and aromatic) and carbohydrates, including their behaviour, have been
      reported in many works. However, knowledge on the occurrence and behaviour of D
      enantiomers of organic acids, which may be abundant in soil, is currently
      lacking. Also, identification of the impact and mechanisms of environmental
      factors, such as soil water content, on carbohydrate status within soil organic
      matter remains to be determined. Finally, the occurrence of vitamins in soil and
      their role in biological and biochemical soil processes represent an important
      direction for future research. 

PMID- 24319375
TI  - Noise-assisted concurrent multipath traffic distribution in ad hoc networks.
AB  - The concept of biologically inspired networking has been introduced to tackle
      unpredictable and unstable situations in computer networks, especially in
      wireless ad hoc networks where network conditions are continuously changing,
      resulting in the need of robustness and adaptability of control methods.
      Unfortunately, existing methods often rely heavily on the detailed knowledge of
      each network component and the preconfigured, that is, fine-tuned, parameters. In
      this paper, we utilize a new concept, called attractor perturbation (AP), which
      enables controlling the network performance using only end-to-end information.
      Based on AP, we propose a concurrent multipath traffic distribution method, which
      aims at lowering the average end-to-end delay by only adjusting the transmission
      rate on each path. We demonstrate through simulations that, by utilizing the
      attractor perturbation relationship, the proposed method achieves a lower average
      end-to-end delay compared to other methods which do not take fluctuations into
      account. 

PMID- 24319376
TI  - Drought tolerance in wheat.
AB  - Drought is one of the most important phenomena which limit crops' production and
      yield. Crops demonstrate various morphological, physiological, biochemical, and
      molecular responses to tackle drought stress. Plants' vegetative and reproductive
      stages are intensively influenced by drought stress. Drought tolerance is a
      complicated trait which is controlled by polygenes and their expressions are
      influenced by various environmental elements. This means that breeding for this
      trait is so difficult and new molecular methods such as molecular markers,
      quantitative trait loci (QTL) mapping strategies, and expression patterns of
      genes should be applied to produce drought tolerant genotypes. In wheat, there
      are several genes which are responsible for drought stress tolerance and produce
      different types of enzymes and proteins for instance, late embryogenesis abundant
      (lea), responsive to abscisic acid (Rab), rubisco, helicase, proline, glutathione
      S-transferase (GST), and carbohydrates during drought stress. This review paper
      has concentrated on the study of water limitation and its effects on
      morphological, physiological, biochemical, and molecular responses of wheat with
      the possible losses caused by drought stress. 

PMID- 24319377
TI  - Dimensionality of the Wisconsin Schizotypy Scales--brief forms in college
      students.
AB  - Wisconsin Schizotypy Scales are one of the most used measuring instruments for
      the assessment of psychometric risk for psychosis. The main goal of the present
      study was to analyze the internal structure of the Wisconsin Schizotypy Scales
      Brief (WSS-B) forms and the reliability of the scores in a large sample of
      college students. The final sample was comprised by a total of 1349 students, 288
      males, with a mean age of 20.48 years (SD = 2.58). The results indicated that the
      WSS-B scores presented adequate psychometric properties. Cronbach's alfa
      coefficient for total scores in WSS-B ranged from 0.86 to 0.93. Analysis of the
      internal structure of the WSS-B, through confirmatory factor analysis and
      exploratory structural equation modeling, yielded a four factor solution (Magical
      Ideation, Perceptual Aberration, Social Anhedonia, and Physical Anhedonia) as the
      most adequate. Statistically significant differences in mean scores of WSS-B by
      sex were found. These results provided new validity evidence of the WSS-B scores
      in an independent sample of nonclinical young adults. The WSS-B seems to be
      useful, brief, and easy to administrate for the screening of extended psychosis
      phenotype in the general population. 

PMID- 24319379
TI  - A note on decomposing a square matrix as sum of two square nilpotent matrices
      over an arbitrary field.
AB  - Let K be an arbitrary field and X a square matrix over K. Then X is sum of two
      square nilpotent matrices over K if and only if, for every algebraic extension L
      of K and arbitrary nonzero alpha ? L, there exist idempotent matrices P 1 and P 2
      over L such that X = alphaP 1 - alphaP 2. 

PMID- 24319378
TI  - Comparison of long-term effect of dual-chamber pacing and alcohol septal ablation
      in patients with hypertrophic obstructive cardiomyopathy.
AB  - INTRODUCTION: Nonpharmacological treatment of patients with hypertrophic
      obstructive cardiomyopathy (HOCM) comprises surgical myectomy (SME), alcohol
      septal ablation (ASA), and dual-chamber (DDD) pacing. The aim of the study was to
      compare the long-term effect of DDD pacing and ASA in symptomatic HOCM patients.
      PATIENTS AND METHODS: We evaluated retrospective data from three cardiocenters;
      there were 24 patients treated with DDD pacing included and 52 treated with ASA
      followed for 101 +/- 49 and 87 +/- 23 months, respectively. RESULTS: In the group
      treated with DDD pacing, the left ventricle outflow tract gradient (LVOTG)
      decreased from 82 +/- 44 mmHg to 21 +/- 21 mmHg, and NYHA class improved from 2.7
      +/- 0.5 to 2.1 +/- 0.6 (both P < 0.001). In the ASA-treated group, a decline in
      LVOTG from 73 +/- 38 mmHg to 24 +/- 26 mmHg and reduction in NYHA class from 2.8
      +/- 0.5 to 1.7 +/- 0.8 were observed (both P < 0.001). The LVOTG change was
      similar in both groups (P = 0.264), and symptoms were more affected by ASA (P =
      0.001). CONCLUSION: ASA and DDD pacing were similarly effective in reducing
      LVOTG. The symptoms improvement was more expressed in patients treated with ASA.

PMID- 24319380
TI  - Characterization of cellulolytic bacterial cultures grown in different
      substrates.
AB  - Nine aerobic cellulolytic bacterial cultures were obtained from the Leibniz
      Institute DSMZ-German Collection of Microorganisms and Cell Culture (DSMZ) and
      the American Type Culture Collection (ATCC). The objectives of this study were to
      characterize the cellulolytic bacteria and to determine the optimum moisture
      ratio required for solid state fermentation (SSF) of palm kernel cake (PKC). The
      bacteria cultures were grown on reconstituted nutrient broth, incubated at 30
      degrees C and agitated at 200 rpm. Carboxymethyl cellulase, xylanase, and
      mannanase activities were determined using different substrates and after SSF of
      PKC. The SSF was conducted for 4 and 7 days with inoculum size of 10% (v/w) on
      different PKC concentration-to-moisture ratios: 1 : 0.2, 1 : 0.3, 1 : 0.4, and 1
      : 0.5. Results showed that Bacillus amyloliquefaciens 1067 DSMZ, Bacillus
      megaterium 9885 ATCC, Paenibacillus curdlanolyticus 10248 DSMZ, and Paenibacillus
      polymyxa 842 ATCC produced higher enzyme activities as compared to other
      bacterial cultures grown on different substrates. The cultures mentioned above
      also produced higher enzyme activities when they were incubated under SSF using
      PKC as a substrate in different PKC-to-moisture ratios after 4 days of
      incubation, indicating that these cellulolytic bacteria can be used to degrade
      and improve the nutrient quality of PKC. 

PMID- 24319381
TI  - Authentication of Nigella sativa seed oil in binary and ternary mixtures with
      corn oil and soybean oil using FTIR spectroscopy coupled with partial least
      square.
AB  - Fourier transform infrared spectroscopy (FTIR) combined with multivariate
      calibration of partial least square (PLS) was developed and optimized for the
      analysis of Nigella seed oil (NSO) in binary and ternary mixtures with corn oil
      (CO) and soybean oil (SO). Based on PLS modeling performed, quantitative analysis
      of NSO in binary mixtures with CO carried out using the second derivative FTIR
      spectra at combined frequencies of 2977-3028, 1666-1739, and 740-1446 cm(-1)
      revealed the highest value of coefficient of determination (R (2), 0.9984) and
      the lowest value of root mean square error of calibration (RMSEC, 1.34% v/v). NSO
      in binary mixtures with SO is successfully determined at the combined frequencies
      of 2985-3024 and 752-1755 cm(-1) using the first derivative FTIR spectra with R
      (2) and RMSEC values of 0.9970 and 0.47% v/v, respectively. Meanwhile, the second
      derivative FTIR spectra at the combined frequencies of 2977-3028 cm(-1), 1666
      1739 cm(-1), and 740-1446 cm(-1) were selected for quantitative analysis of NSO
      in ternary mixture with CO and SO with R (2) and RMSEC values of 0.9993 and 0.86%
      v/v, respectively. The results showed that FTIR spectrophotometry is an accurate
      technique for the quantitative analysis of NSO in binary and ternary mixtures
      with CO and SO. 

PMID- 24319382
TI  - An expansion formula with higher-order derivatives for fractional operators of
      variable order.
AB  - We obtain approximation formulas for fractional integrals and derivatives of
      Riemann-Liouville and Marchaud types with a variable fractional order. The
      approximations involve integer-order derivatives only. An estimation for the
      error is given. The efficiency of the approximation method is illustrated with
      examples. As applications, we show how the obtained results are useful to solve
      differential equations, and problems of the calculus of variations that depend on
      fractional derivatives of Marchaud type. 

PMID- 24319383
TI  - A relation routing scheme for distributed semantic media query.
AB  - Performing complex semantic queries over large-scale distributed media contents
      is a challenging task for rich media applications. The dynamics and openness of
      data sources make it uneasy to realize a query scheme that simultaneously
      achieves precision, scalability, and reliability. In this paper, a novel relation
      routing scheme (RRS) is proposed by renovating the routing model of Content
      Centric Network (CCN) for directly querying large-scale semantic media content.
      By using proper query model and routing mechanism, semantic queries with complex
      relation constrains from users can be guided towards potential media sources
      through semantic guider nodes. The scattered and fragmented query results can be
      integrated on their way back for semantic needs or to avoid duplication. Several
      new techniques, such as semantic-based naming, incomplete response avoidance,
      timeout checking, and semantic integration, are developed in this paper to
      improve the accuracy, efficiency, and practicality of the proposed approach. Both
      analytical and experimental results show that the proposed scheme is a promising
      and effective solution for complex semantic queries and integration over large
      scale networks. 

PMID- 24319384
TI  - Three colossal neurons: a new approach to an old classroom demonstration.
AB  - Research suggests that the key to optimal student learning, regardless of class
      size, is engaging students in active learning. It is my contention that to truly
      understand neural processing, one must not only understand the activities of the
      neuron as a living cell, but also how that cell works within the context of a
      neural network. The demonstration exercise described herein combines techniques
      expressed in three previously published articles, with certain modifications,
      allowing as few as 15 and as many as about 200 students to actively participate
      in the endeavor. Moreover, test scores from 158 students were examined, showing
      that students who participated in the demonstration performed significantly
      better on exam questions than students who did not take part. 

PMID- 24319385
TI  - MetaNeuron: A Free Neuron Simulation Program for Teaching Cellular
      Neurophysiology.
AB  - MetaNeuron, a neuron simulation program, is an effective interactive tool for
      teaching cellular neurophysiology. The computer program simulates a wide range of
      neuronal behavior in its six lessons: i) Resting Membrane Potential, ii) Membrane
      Time Constant, iii) Membrane Length Constant, iv) Axon Action Potential, v) Axon
      Voltage Clamp, and vi) Synaptic Potential. The program is designed foremost as a
      platform for conducting neurophysiology experiments in silico. Neuronal
      parameters are easily modified and a virtual stimulator injects single or double
      current pulses into the neuron. Phenomena such as temporal summation of synaptic
      potentials, passive spread of a synaptic potential from the dendrite to the soma,
      the refractory period, families of voltage-clamp traces, and the reversal
      potential of synaptic responses, are easily illustrated in MetaNeuron. Responses
      are displayed graphically and can be measured with a cursor. Families of traces
      can be generated and viewed in rotatable 3D plots. Mac and Windows versions of
      the program can be downloaded, free of charge, onto individual student computers
      from the website www.MetaNeuron.org. A manual containing operating instructions,
      a description of the lessons, and exercises conducted on MetaNeuron, can also be
      downloaded for free. 

PMID- 24319386
TI  - Using case studies as a semester-long tool to teach neuroanatomy and structure
      function relationships to undergraduates.
AB  - In addition to being inherently interesting to students, case studies can serve
      as useful tools to teach neuroanatomy and demonstrate important relationships
      between brain structure and function. In most undergraduate courses, however,
      neuroanatomy is presented to students as a "unit" or chapter, much like other
      topics (e.g., receptors, pharmacology) covered in the course, over a period of a
      week or two. In this article, a relatively simple model of teaching neuroanatomy
      is described in which students are actively engaged in the presentation and
      discussion of case studies throughout the semester, following a general
      introduction to the structure of the nervous system. In this way, the teaching of
      neuroanatomy is "distributed" throughout the semester and put into a more user
      friendly context for students as additional topics are introduced. Generally,
      students report enjoying learning brain structure using this method, and
      commented positively on the class activities associated with learning brain
      anatomy. Advantages and disadvantages of such a model are presented, as are
      suggestions for implementing similar models of undergraduate neuroanatomy
      education. 

PMID- 24319387
TI  - Can You Change a Student's Mind in a Course about the Brain? Belief Change
      Following an Introductory Course in Biological Psychology.
AB  - Undergraduate courses in the neurosciences, including biological psychology,
      often appeal to students because they offer perspectives on human behavior and
      experience that are so different from those students arrive with or are exposed
      to elsewhere on campus. Consider, for example, this passage from Crick's,
      Astonishing Hypothesis: "You, your joys and your sorrows, your memories and your
      ambitions, your sense of personal identity and free will, are in fact no more
      than the behaviour of a vast assembly of nerve cells and their associated
      molecules." Unfortunately, because this perspective is at such odds with those
      many students arrive with, the very thing that makes these classes so interesting
      is also likely to engender resistance. With Crick's hypothesis serving as the
      theme of my introductory course in biological psychology, we explore the ways in
      which complex experiences and behaviors can be explained by lower-level,
      biological phenomena. Historically, and for a host of valid reasons, class
      assessment tends to focus on whether students understand the course material
      (e.g., Can you explain the role of Ca(2+) in synaptic transmission?), rather than
      whether students believe what they have been introduced to (e.g., Do you believe
      that the mind exists as something separate from the body?). For a number of
      years, however, I have also been collecting pre- and post-test data from students
      enrolled in three formats of the class in an effort to measure changes in
      beliefs. One format was a conventional standalone class, whereas the other two
      were more intensive and involved parallel coursework in the Philosophy of Mind
      with a second instructor. The full assessment, identical at both test intervals,
      was comprised of 56 items and included 16 items from a Theoretical Orientation
      Scale (TOS; Coan, 1979), several of which addressed whether human behavior was
      predictable; 14 items that addressed dualism, the veracity of our perceptions,
      personal responsibility, and other topics; and 26 items from the Organicism
      Mechanism Paradigm Inventory (OMPI; Germer et al., 1982). Unlike most of the
      other test items, which addressed class topics specifically, the OMPI addressed
      general worldviews between two poles of mechanism and organicism. Mechanistic
      explanations, common in Neuroscience, tend to be highly reductive and treat
      organisms as more passive and reactive, whereas organismic explanations treat
      organisms as more active and the systems that give rise to their behaviors as non
      reductive. Overall, analyses revealed statistically significant changes on a wide
      range of items that were generally, though not always, consistent with course
      objectives. The results of the OMPI indicated that the average student began the
      term closer to the organismic end of the scale, and became slightly more
      organismic by the end of the term. And yet, on a number of items related more
      specifically to the relationship between brain and behavior, students became more
      willing to endorse reductive and mechanistic positions. Although student beliefs
      can be very resistant to persuasion, change can occur. 

PMID- 24319388
TI  - Pleasure and pain: teaching neuroscientific principles of hedonism in a large
      general education undergraduate course.
AB  - In a large (250 registrants) general education lecture course, neuroscience
      principles were taught by two professors as co-instructors, starting with simple
      brain anatomy, chemistry, and function, proceeding to basic brain circuits of
      pleasure and pain, and progressing with fellow expert professors covering
      relevant philosophical, artistic, marketing, and anthropological issues. With
      this as a base, the course wove between fields of high relevance to psychology
      and neuroscience, such as food addiction and preferences, drug seeking and
      craving, analgesic pain-inhibitory systems activated by opiates and stress,
      neuroeconomics, unconscious decision-making, empathy, and modern neuroscientific
      techniques (functional magnetic resonance imaging and event-related potentials)
      presented by the co-instructors and other Psychology professors. With no formal
      assigned textbook, all lectures were PowerPoint-based, containing links to
      supplemental public-domain material. PowerPoints were available on Blackboard
      several days before the lecture. All lectures were also video-recorded and posted
      that evening. The course had a Facebook page for after-class conversation and one
      of the co-instructors communicated directly with students on Twitter in real time
      during lecture to provide momentary clarification and comment. In addition to
      graduate student Teaching Assistants (TAs), to allow for small group discussion,
      ten undergraduate students who performed well in a previous class were selected
      to serve as discussion leaders. The Discussion Leaders met four times at
      strategic points over the semester with groups of 20-25 current students, and
      received one credit of Independent Study, thus creating a course within a course.
      The course grade was based on weighted scores from two multiple-choice exams and
      a five-page writing assignment in which each student reviewed three unique, but
      brief original peer-review research articles (one page each) combined with
      expository writing on the first and last pages. A draft of the first page,
      collected early in the term, was returned to each student by graduate TAs to
      provide individual feedback on scientific writing. Overall the course has run
      three times at ful or near enrollment capacity despite being held at an 8:00 AM
      time slot. Student-generated teaching evaluations place it well within the normal
      range, while this format importantly contributes to budget efficiency permitting
      the teaching of more required small-format courses (e.g., freshman writing). The
      demographics of the course have changed to one in which the vast majority of the
      students are now outside the disciplines of neuroscience or psychology and are
      taking the course to fulfill a General Education requirement. This pattern allows
      the wide dissemination of basic neuroscientific knowledge to a general college
      audience. 

PMID- 24319389
TI  - Engaging the audience: developing presentation skills in science students.
AB  - This article describes a graduate class in presentation skills ("PClass") as a
      model for how a class with similar objectives, expectations and culture might be
      mounted for undergraduates. The required class is given for students in
      neuroscience and physiology programs at the University of North Carolina at
      Chapel Hill; I describe the class in the years I led it, from 2003-2012. The
      class structure centered on peer rehearsal, critiquing of PowerPoint, and chalk
      talks by the students; video-recording of student talks for later review by the
      student with the instructor; and presentation of polished talks in a formal
      setting. A different faculty visitor to the class each week gave the students a
      variety of perspectives. The students also gained insight into their own evolving
      skills by discussing the strengths and weaknesses of seminars given by visitors
      to the campus. A unique feature of the class was collaboration with a
      professional actor from the University's Department of Dramatic Arts, who helped
      the students develop techniques for keeping the attention of an audience, for
      speaking with confidence, and for controlling nervousness. The undergraduate
      campus would be expected to lend itself to this sort of interdisciplinary faculty
      cooperation. In addition, students worked on becoming adept at designing and
      presenting posters, introducing speakers graciously and taking charge of the
      speaker's question session, and speaking to a lay audience. 

PMID- 24319390
TI  - The use of haiku to convey complex concepts in neuroscience.
AB  - Conveying scientific content with accuracy and fluency takes practice and
      requires deep understanding of the concepts being conveyed. This depth of
      knowledge comes from internalizing information and constructing it into a form
      that is unique and coherent to the individual. Often in science classrooms there
      is little or no opportunity for students to practice this type of thinking,
      activities that we believe are fundamental to effective science communication.
      This article describes the use of haiku - a 17 syllable poem - as a means for
      students to convey neurobiological concepts in a succinct manner by forcing them
      to focus on the most salient features of the observed processes. In our
      assignments haiku writing was successfully paired with explanations of the
      students' thought processes (Addiction course) or the scientific evidence to
      support claims (Neurodegenerative Disease course). We provide examples of student
      haiku and explanations as evidence of the power of this approach. The coupling of
      poetry and prose together create rich, accurate descriptions of scientific
      phenomena by encouraging higher-order thinking. Poetry writing can thus be used
      across the curriculum to forge comprehension of complex ideas in any discipline
      and to bridge the arts and the sciences. 

PMID- 24319391
TI  - Basic neuron model electrical equivalent circuit: an undergraduate laboratory
      exercise.
AB  - We developed a hands-on laboratory exercise for undergraduate students in which
      they can build and manipulate a neuron equivalent circuit. This exercise uses
      electrical circuit components that resemble neuron components and are easy to
      construct. We describe the methods for creating the equivalent circuit and how to
      observe different neuron properties through altering the structure of the
      equivalent circuit. We explain how this hands-on laboratory activity allows for
      the better understanding of this fundamental neuroscience concept. At the
      conclusion of this laboratory exercise, undergraduate students will be able to
      apply the principles of Ohm's law, cable theory with regards to neurons, and
      understand the functions of resistance and capacitance in a neuron. 

PMID- 24319392
TI  - Community-based, Experiential Learning for Second Year Neuroscience
      Undergraduates.
AB  - Service learning is becoming a keystone of the undergraduate learning experience.
      At Stonehill College, we implemented a service learning course, called a Learning
      Community, in Neuroscience. This course was created to complement the basic
      research available to Stonehill Neuroscience majors with experience in a more
      applied and "clinical" setting. The Neuroscience Learning Community is designed
      to promote a deep understanding of Neuroscience by combining traditional
      classroom instruction with clinical perspectives and real-life experiences. This
      Neuroscience Learning Community helps students translate abstract concepts within
      the context of neurodevelopment by providing students with contextual experience
      in a real-life, unscripted setting. The experiential learning outside of the
      classroom enabled students to participate in informed discussions in the
      classroom, especially with regard to neurodevelopmental disorders. We believe
      that all students taking this course gain an understanding of the importance of
      basic and applied Neuroscience as it relates to the individual and the community.
      Students also have used this concrete, learning-by-doing experience to make
      informed decisions about career paths and choice of major. 

PMID- 24319393
TI  - Studying temporal properties of stimulus-evoked responses in the ventral nerve
      cord of insects.
AB  - Students in undergraduate laboratory settings learn many of the foundational
      principles of sensory processing in the comparatively simple, easy to study
      invertebrate nervous system. In this example preparation, the American cockroach,
      students record action potentials from the fibers in the ventral nerve cord (VNC)
      that participate in a well explained escape behavior in response to stimulation
      of its cerci, a pair of mechanosensitive abdominal appendages. A system that
      allows good control over the time and amplitude of the air pulse delivered to the
      cerci is described. This experimental setup enables students to extract and
      display temporal information from recordings to learn how to interpret those
      responses in the context of the properties of the stimulus. I offer examples of
      specific investigations and analyses that work well for this purpose in an
      undergraduate laboratory. 

PMID- 24319394
TI  - Using crickets to introduce neurophysiology to early undergraduate students.
AB  - Anatomy and physiology instructors often face the daunting task of teaching the
      principles of neurophysiology as part of a laboratory course with very limited
      resources. Teaching neurophysiology can be a difficult undertaking as
      sophisticated electrophysiology and data acquisition equipment is often
      financially out-of-reach for two-year institutions, and for many preparations,
      instructors need to be highly skilled in electrophysiology techniques when
      teaching hands-on laboratories. In the absence of appropriate laboratory tools,
      many undergraduate students have difficulty understanding concepts related to
      neurophysiology. The cricket can serve as a reliable invertebrate model to teach
      the basic concepts of neurophysiology in the educational laboratory. In this
      manuscript, we describe a series of hands-on, demonstrative, technologically
      simple, and affordable laboratory activities that will help undergraduate
      students gain an understanding of the principles of neurophysiology. By using the
      cerci ganglion and leg preparation, students can quantify extracellular neural
      activity in response to sensory stimulation, understand the principles of rate
      coding and somatotopy, perform electrical microstimulation to understand the
      threshold of sensory stimulation, and do pharmacological manipulation of neuronal
      activity. We describe the utility of these laboratory activities, provide a
      convenient protocol for quantifying extracellular recordings, and discuss
      feedback provided by undergraduate students with regards to the quality of the
      educational experience after performing the lab activities. 

PMID- 24319395
TI  - The Use of Mock NSF-type Grant Proposals and Blind Peer Review as the Capstone
      Assignment in Upper-Level Neurobiology and Cell Biology Courses.
AB  - Although the use of grant proposals and blind peer review are standard in the
      natural sciences, their use as a pedagogical tool is rarely mentioned in the
      literature. As a consequence of dissatisfaction with term papers and literature
      reviews as the capstone writing experience in 300-level undergraduate biology
      courses, I have been experimenting with mock NSF-type grant proposals followed by
      blind peer review as the major assignment in my junior/senior-level classes. The
      improvement in educational outcomes and competencies due to this assignment
      appears to be substantial and worth the additional effort on both the students'
      and instructor's parts. Here, I outline the mechanics of this assignment and its
      advantages and disadvantages as well as the type of curriculum that is required
      to support this type of capstone assignment. 

PMID- 24319396
TI  - Engaging Undergraduates in a Unique Neuroscience Research Opportunity: A
      Collaborative Research Experience Between a Primarily Undergraduate Institution
      (PUI) and a Major Research Institution.
AB  - This report describes a unique undergraduate research and teaching collaboration
      between investigators at two institutions, one a relatively small, primarily
      undergraduate institution and the other a large, urban research-intensive
      university. The program incorporates three major facets. First, undergraduates
      participate in a weekly collaborative lab meeting involving instructors from both
      institutions and held via remote video. Student-led discussions and presentations
      dominate these meetings, and the unique format promotes novel interactions
      between students and instructors. Second, students carry out investigative
      studies centered on understanding the role extracellular pH dynamics play in
      regulating neuronal processing. Students carry out studies on isolated neurons
      and glia throughout the fall and spring semesters, and primarily use a
      noninvasive electrophysiological technique, termed self-referencing, for
      extracellular pH measurements. The technique is relatively simple and readily
      learned and employed by undergraduates, while still being powerful enough to
      provide novel and meaningful research results. The research component is expanded
      for several students each summer who are selected to participate in summer
      research with both PIs and graduate students at the major research institution.
      Finally results gathered during the year and over the summer are disseminated at
      institutional symposia, undergraduate neuroscience symposia, national society
      meetings, and in submitted journal manuscripts. Preliminary observations and
      findings over three years support the aim of this research experience; to create
      a productive environment that facilitates deep-level understanding of
      neurophysiological concepts at the undergraduate level and promotes intellectual
      development while cultivating an excitement for scientific inquiry in the present
      and future. 

PMID- 24319397
TI  - A win for science: the benefits of mentoring high school students in the lab.

PMID- 24319398
TI  - Training Tomorrow's Neuroscientists Today.

PMID- 24319399
TI  - Science Communication to the General Public: Why We Need to Teach Undergraduate
      and Graduate Students this Skill as Part of Their Formal Scientific Training.

PMID- 24319400
TI  - Harnessing poverty alleviation to reduce the stigma of HIV in Sub-Saharan Africa.
AB  - Alexander Tsai and colleagues highlight the complex relationship between poverty
      and HIV stigma in sub-Saharan Africa, and discuss possible ways to break the
      cycle. Please see later in the article for the Editors' Summary. 

PMID- 24319401
TI  - Synthesis, Characterization, and Bioactivity of Schiff Bases and Their Cd(2+),
      Zn(2+), Cu(2+), and Ni(2+) Complexes Derived from Chloroacetophenone Isomers with
      S-Benzyldithiocarbazate and the X-Ray Crystal Structure of S-Benzyl- beta -N-(4
      chlorophenyl)methylenedithiocarbazate.
AB  - Two bidentate Schiff base ligands having nitrogen sulphur donor sequence were
      derived from the condensation of S-benzyldithiocarbazate (SBDTC) with 2
      chloroacetophenone and 4-chloroacetophenone to give S-benzyl- beta -N-(2
      chlorophenyl)methylenedithiocarbazate (NS2) and S-benzyl- beta -N-(4
      chlorophenyl)methylenedithiocarbazate (NS4) isomers. Each of the ligands was then
      chelated with Cd(2+), Zn(2+), Cu(2+), and Ni(2+). The compounds were
      characterized via IR spectroscopy and melting point while the structure of NS4
      was revealed via X-ray crystallography. Finally, the compounds were screened for
      antimicrobial activity to investigate the effect that is brought by the
      introduction of the chlorine atom to the benzene ring. X-ray crystallographic
      analysis showed that the structure of NS4 is planar with a phenyl ring that is
      nearly perpendicular to the rest of the molecules. The qualitative antimicrobial
      assay results showed that NS4 and its complexes lacked antifungal activity while
      Gram-positive bacteria were generally inhibited more strongly than Gram-negative
      bacteria. Furthermore, NS4 metal complexes were inhibited more strongly than the
      ligand while the opposite was seen with NS2 ligand and its complexes due to the
      partial solubility in dimethyl sulfoxide (DMSO). It was concluded that generally
      NS2 derivatives have higher bioactivity than that of NS4 derivatives and that the
      Cd complexes of both ligands have pronounced activity specifically on K.
      rhizophila. 

PMID- 24319403
TI  - Granulocyte colony-stimulating factor-producing esophageal squamous cell
      carcinoma following chemoradiotherapy and bone marrow transplantation for acute
      lymphoblastic leukemia.
AB  - A 30-year-old man, who had been treated with craniospinal irradiation, total-body
      irradiation, and bone marrow transplantation for acute lymphoblastic leukemia at
      20 years of age, complained of dysphagia. The patient had spike fever with
      leukocytosis (19,020/MUl). Serum granulocyte colony-stimulating factor (G-CSF)
      level was also increased (53.7 pg/ml). Immunohistochemistry revealed positive
      staining for anti-G-CSF antibody in carcinoma cells obtained by endoscopic
      biopsy. The patient was diagnosed with G-CSF-producing locally advanced
      esophageal squamous cell carcinoma. The clinical diagnosis was T4; tumor invaded
      aorta, with regional lymph node metastases (N1). The patient underwent
      transthoracic esophagectomy with three-field lymph node dissection and gastric
      tube reconstruction following a radiation dose of 41.4 Gy with 5-fluorouracil
      continuous infusion as neoadjuvant therapy. There were no viable cancer cells in
      the resected esophageal specimen and lymph nodes. The patient had no evidence for
      typical risk factors for developing esophageal cancer. After the operation,
      neutrophils and G-CSF decreased to normal levels. The patient had recurrence of
      regional and distant multiple lymph node metastases at 3 months after operation.

PMID- 24319402
TI  - A case report of pulmonary tumor thrombotic microangiopathy (PTTM) caused by
      esophageal squamous cell carcinoma.
AB  - A 67-year-old male was referred to our hospital after being diagnosed with
      esophageal squamous cell carcinoma of the middle thoracic esophagus. The clinical
      stage was T1b(sm)N4M1 cStage IVb, so he was admitted to our hospital for systemic
      chemotherapy. He had sustained fever and a dry cough. Chest computed tomography
      showed the presence of irregular shadows, and unidentified respiratory
      insufficiency had progressed. A transbronchial lung biopsy revealed a pulmonary
      artery tumor embolus of esophageal squamous cell carcinoma. He developed DIC and
      died of respiratory failure on the 19th hospital day. The postmortem autopsy
      detected pulmonary tumor thrombotic microangiopathy accompanied by esophageal
      squamous cell carcinoma.

PMID- 24319404
TI  - The rise and fall of women's advantage: a comparison of national trends in life
      expectancy at age 65 years.
AB  - The female advantage in life expectancy (LE) is found worldwide, despite
      differences in living conditions, the status of women and other factors. However,
      this advantage has decreased in recent years in low-mortality countries. Few
      researchers have looked at the gender gap in LE in old age (age 65) in a longer
      historical perspective. Have women always had an advantage in LE at old age and
      do different countries share the same trends? Life expectancy data for 17
      countries were assessed from Human Mortality Database from 1751 to 2007. Since
      most of the changes in LE taking place today are driven by reductions of old age
      mortality the gender difference in LE was calculated at age 65. Most low
      mortality countries show the same historical trend, a rise and fall of women's
      advantage in LE at age 65. Three phases that all but two countries passed through
      were discerned. After a long phase with a female advantage in LE at 65 of <1
      year, the gender gap increased significantly during the twentieth century. The
      increase occurred in all countries but at different time points. Some countries
      such as England and France had an early rise in female advantage (1900-1919),
      while it occurred 50 years later in Sweden, Norway and in the Netherlands. The
      rise was followed by a more simultaneous fall in female advantage in the studied
      countries towards the end of the century, with exceptions of Japan and Spain. The
      different timing regarding the increase of women's advantage indicates that
      country-specific factors may have driven the rise in female advantage, while
      factors shared by all countries may underlie the simultaneous fall. More
      comprehensive, multi-disciplinary study of the evolution of the gender gap in old
      age could provide new hypotheses concerning the determinants of gendered
      differences in mortality.

PMID- 24319405
TI  - Factors influencing decision-making by social care and health sector
      professionals in cases of elder financial abuse.
AB  - This study aimed to identify the factors that have the greatest influence on UK
      social care and health sector professionals' certainty that an older person is
      being financially abused, their likelihood of intervention, and the type of
      action most likely to be taken. A factorial survey approach, applying a
      fractional factorial design, was used. Health and social care professionals (n =
      152) viewed a single sample of 50 elder financial abuse case vignettes; the
      vignettes contained seven pieces of information (factors). Following multiple
      regression analysis, incremental F tests were used to compare the impact of each
      factor on judgements. Factors that had a significant influence on judgements of
      certainty that financial abuse was occurring included the older person's mental
      capacity and the nature of the financial problem suspected. Mental capacity
      accounted for more than twice the variance in likelihood of action than the type
      of financial problem. Participants from social care were more likely to act and
      chose more actions compared to health sector participants. The results are
      discussed in relation to a bystander intervention model. The impact of the older
      person's mental capacity on decision-making suggests the need for training to
      ensure action is also taken in cases where older people have full mental capacity
      and are being abused. Training also needs to highlight the more subtle types of
      financial abuse, the types that appear not to lead to certainty or action.

PMID- 24319406
TI  - Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue.
AB  - Heart failure is a major international health issue. Myocardial mass loss and
      lack of contractility are precursors to heart failure. Surgical demand for
      effective myocardial repair is tempered by a paucity of appropriate biological
      materials. These materials should conveniently replicate natural human tissue
      components, convey persistent elasticity, promote cell attachment, growth and
      conformability to direct cell orientation and functional performance. Here,
      microfabrication techniques are applied to recombinant human tropoelastin, the
      resilience-imparting protein found in all elastic human tissues, to generate
      photocrosslinked biological materials containing well-defined micropatterns.
      These highly elastic substrates are then used to engineer biomimetic cardiac
      tissue constructs. The micropatterned hydrogels, produced through
      photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment,
      spreading, alignment, function, and intercellular communication of cardiomyocytes
      by providing an elastic mechanical support that mimics their dynamic mechanical
      properties in vivo. The fabricated MeTro hydrogels also support the synchronous
      beating of cardiomyocytes in response to electrical field stimulation. These
      novel engineered micropatterned elastic gels are designed to be amenable to 3D
      modular assembly and establish a versatile, adaptable foundation for the modeling
      and regeneration of functional cardiac tissue with potential for application to
      other elastic tissues.

PMID- 24319407
TI  - Nutritional adequacy of diets containing growing up milks or unfortified cow's
      milk in Irish children (aged 12-24 months).
AB  - BACKGROUND: Growing up milks (GUM) are milk-based drinks with added vitamins and
      minerals intended for children aged 12-36 months. Few data are available on the
      consumption of GUM and their role in the diets of young children. OBJECTIVE: To
      determine the nutritional adequacy of two groups of 12-24-month-old Irish
      children by type of milk consumption (consumers or non-consumers of GUM). DESIGN:
      Using data from a cross-sectional study of Irish children, the National Pre
      School Nutrition Survey (2010-2011), two groups of children were defined. The
      groups included children aged 12-24 months with an average daily total milk
      intake of at least 300 g and consuming GUM (>=100 g/day) together with cow's milk
      (n=29) or cow's milk only (n=56). RESULTS: While average total daily energy
      intakes were similar in both consumers and non-consumers of GUM, intakes of
      protein, saturated fat, and vitamin B12 were lower and intakes of carbohydrate,
      dietary fibre, iron, zinc, vitamins C and D were higher in consumers of GUM.
      These differences in nutrient intakes are largely attributable to the differences
      in composition between GUM and cow's milk. For both consumers and non-consumers
      of GUM, intakes of carbohydrate and fat were generally in line with
      recommendations while intakes of protein, dietary fibre and most micronutrients
      were adequate. For children consuming cow's milk only, high proportions had
      inadequate intakes of iron and vitamin D; however, these proportions were much
      lower in consumers of GUM. CONCLUSIONS: Consumption of GUM reduced the risk of
      inadequacies of iron and vitamin D, two nutrients frequently lacking in the diets
      of young children consuming unfortified cow's milk only.

PMID- 24319408
TI  - Real-time biomimetic Central Pattern Generators in an FPGA for hybrid
      experiments.
AB  - This investigation of the leech heartbeat neural network system led to the
      development of a low resources, real-time, biomimetic digital hardware for use in
      hybrid experiments. The leech heartbeat neural network is one of the simplest
      central pattern generators (CPG). In biology, CPG provide the rhythmic bursts of
      spikes that form the basis for all muscle contraction orders (heartbeat) and
      locomotion (walking, running, etc.). The leech neural network system was
      previously investigated and this CPG formalized in the Hodgkin-Huxley neural
      model (HH), the most complex devised to date. However, the resources required for
      a neural model are proportional to its complexity. In response to this issue,
      this article describes a biomimetic implementation of a network of 240 CPGs in an
      FPGA (Field Programmable Gate Array), using a simple model (Izhikevich) and
      proposes a new synapse model: activity-dependent depression synapse. The network
      implementation architecture operates on a single computation core. This digital
      system works in real-time, requires few resources, and has the same bursting
      activity behavior as the complex model. The implementation of this CPG was
      initially validated by comparing it with a simulation of the complex model. Its
      activity was then matched with pharmacological data from the rat spinal cord
      activity. This digital system opens the way for future hybrid experiments and
      represents an important step toward hybridization of biological tissue and
      artificial neural networks. This CPG network is also likely to be useful for
      mimicking the locomotion activity of various animals and developing hybrid
      experiments for neuroprosthesis development. 

PMID- 24319409
TI  - A cholinergic hypothesis of the unconscious in affective disorders.
AB  - The interactions between distinct pharmacological systems are proposed as a key
      dynamic in the formation of unconscious memories underlying rumination and mood
      disorder, but also reflect the plastic capacity of neural networks that can aid
      recovery. An inverse and reciprocal relationship is postulated between
      cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor
      transduction facilitates encoding of unconscious, prepotent behavioral
      repertoires at the core of affective disorders and ADHD. Behavioral adaptation to
      new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o)
      and its modulation of M1-plasticity. Reversal of learning is dependent on
      increased phasic activation of midbrain monoaminergic nuclei and is a function of
      hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of
      the hypothalamic-pituitary-adrenal (HPA) axis predicts deficits in hippocampal
      dependent memory and executive function and further impairments to cognitive
      inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signaling
      of monoamines only. A role is proposed for the phasic activation of the basal
      forebrain cholinergic nucleus by cortical projections from the complex consisting
      of the insula and claustrum. Although controversial, recent studies suggest a
      common ontogenetic origin of the two structures and a functional coupling.
      Lesions of the region result in loss of motivational behavior and familiarity
      based judgements. A major hypothesis of the paper is that these lost faculties
      result indirectly, from reduced cholinergic tone. 

PMID- 24319411
TI  - The role of microglia in adult hippocampal neurogenesis.
AB  - Our view of microglia has dramatically changed in the last decade. From cells
      being "silent" in the healthy brain, microglia have emerged to be actively
      involved in several brain physiological functions including adult hippocampal
      neurogenesis, and cognitive and behavioral function. In light of recent
      discoveries revealing a role of microglia as important effectors of neuronal
      circuit reorganization, considerable attention has been focused on how microglia
      and hippocampal neurogenesis could be an interdependent phenomenon. In this
      review the role of microglia in the adult hippocampal neurogenesis under
      physiological condition is discussed. 

PMID- 24319410
TI  - Mixed neurotransmission in the hippocampal mossy fibers.
AB  - The hippocampal mossy fibers (MFs), the axons of the granule cells (GCs) of the
      dentate gyrus, innervate mossy cells and interneurons in the hilus on their way
      to CA3 where they innervate interneurons and pyramidal cells. Synapses on each
      target cell have distinct anatomical and functional characteristics. In recent
      years, the paradigmatic view of the MF synapses being only glutamatergic and,
      thus, excitatory has been questioned. Several laboratories have provided data
      supporting the hypothesis that the MFs can transiently release GABA during
      development and, in the adult, after periods of enhanced excitability. This
      transient glutamate-GABA co-transmission coincides with the transient up
      regulation of the machinery for the synthesis and release of GABA in the
      glutamatergic GCs. Although some investigators have deemed this evidence
      controversial, new data has appeared with direct evidence of co-release of
      glutamate and GABA from single, identified MF boutons. However, this must still
      be confirmed by other groups and with other methodologies. A second, intriguing
      observation is that MF activation produced fast spikelets followed by excitatory
      postsynaptic potentials in a number of pyramidal cells, which, unlike the
      spikelets, underwent frequency potentiation and were strongly depressed by
      activation of metabotropic glutamate receptors. The spikelets persisted during
      blockade of chemical transmission and were suppressed by the gap junction blocker
      carbenoxolone. These data are consistent with the hypothesis of mixed electrical
      chemical synapses between MFs and some pyramidal cells. Dye coupling between
      these types of principal cells and ultrastructural studies showing the co
      existence of AMPA receptors and connexin 36 in this synapse corroborate their
      presence. A deeper consideration of mixed neurotransmission taking place in this
      synapse may expand our search and understanding of communication channels between
      different regions of the mammalian CNS. 

PMID- 24319412
TI  - The trafficking and targeting of P2X receptors.
AB  - The functional expression of P2X receptors at the plasma membrane is dependent on
      their trafficking along secretory and endocytic pathways. There are seven P2X
      receptor subunits, and these differ in their subcellular distributions because
      they have very different trafficking properties. Some are retained within the
      endoplasmic reticulum (ER), while others are predominantly at the cell surface or
      within endosomes and lysosomes. Changes in recruitment of receptors to and from
      the plasma membrane provides a way of rapidly up- or down-regulating the cellular
      response to adenosine triphosphate (ATP). An additional layer of regulation is
      the targeting of these receptors within the membranes of each compartment, which
      affects their stability, function and the nature of the effector proteins with
      which they form signaling complexes. The trafficking and targeting of P2X
      receptors is regulated by their interactions with other proteins and with lipids
      and we can expect this to vary in a cell-type specific manner and in response to
      changes in the environment giving rise to differences in receptor activity and
      function. 

PMID- 24319414
TI  - Multisensory perception and action: development, decision-making, and neural
      mechanisms.

PMID- 24319413
TI  - A dynamic, embodied paradigm to investigate the role of serotonin in decision
      making.
AB  - Serotonin (5-HT) is a neuromodulator that has been attributed to cost assessment
      and harm aversion. In this review, we look at the role 5-HT plays in making
      decisions when subjects are faced with potential harmful or costly outcomes. We
      review approaches for examining the serotonergic system in decision-making. We
      introduce our group's paradigm used to investigate how 5-HT affects decision
      making. In particular, our paradigm combines techniques from computational
      neuroscience, socioeconomic game theory, human-robot interaction, and Bayesian
      statistics. We will highlight key findings from our previous studies utilizing
      this paradigm, which helped expand our understanding of 5-HT's effect on decision
      making in relation to cost assessment. Lastly, we propose a cyclic
      multidisciplinary approach that may aid in addressing the complexity of exploring
      5-HT and decision-making by iteratively updating our assumptions and models of
      the serotonergic system through exhaustive experimentation. 

PMID- 24319415
TI  - Tactile stimulation reduces fear in fish.
AB  - Being groomed or touched can counter stress and negative affect in mammals. In
      two experiments we explored whether a similar phenomenon exists in non-mammals
      like zebrafish. In Experiment 1, we exposed zebrafish to a natural stressor, a
      chemical alarm signal released by injured conspecifics. Before moving them into
      an observation tank, one group of fish was washed and then subjected to a water
      current that served as the tactile stimulus. The other group was simply washed.
      Fish with tactile treatment demonstrated fewer fear behaviors (e.g., bottom
      dwelling) and lower cortisol levels than fish without. In Experiment 2, we
      ascertained a role of somatosensation in these effects. Using a similar paradigm
      as in Experiment 1, we recorded fear behaviors of intact fish and fish with
      damaged lateral line hair cells. Relative to the former, the latter benefited
      less from the tactile stimulus during fear recovery. Together these findings show
      that tactile stimulation can calm fish and that tactile receptors, evolutionarily
      older than those present in mammals, contribute to this phenomenon. 

PMID- 24319417
TI  - Learning and memory with neuropathic pain: impact of old age and progranulin
      deficiency.
AB  - Persistent neuropathic pain is a frequent consequence of peripheral nerve
      injuries, particularly in the elderly. Using the IntelliCage we studied if
      sciatic nerve injury obstructed learning and memory in young and aged mice, each
      in wild type and progranulin deficient mice, which develop premature signs of
      brain aging. Both young and aged mice developed long-term nerve injury-evoked
      hyperalgesia and allodynia. In both genotypes, aged mice with neuropathic pain
      showed high error rates in place avoidance acquisition tasks. However, once
      learnt, these aged mice with neuropathic pain showed a significantly stronger
      maintenance of the aversive memory. Nerve injury did not affect place preference
      behavior in neither genotype, neither in young nor aged mice. However, nerve
      injury in progranulin deficient mice impaired the learning of spatial sequences
      of awarded places, particularly in the aged mice. This task required a
      discrimination of clockwise and anti-clockwise sequences. The chaining failure
      occurred only in progranulin deficient mice after nerve injury, but not in sham
      operated or wildtype mice, suggesting that progranulin was particularly important
      for compensatory adaptations after nerve injury. In contrast, all aged mice with
      neuropathic pain, irrespective of the genotype, had a long maintenance of
      aversive memory suggesting a negative alliance and possibly mutual aggravation of
      chronic neuropathic pain and aversive memory at old age. 

PMID- 24319416
TI  - In sync: gamma oscillations and emotional memory.
AB  - Emotional experiences leave vivid memories that can last a lifetime. The
      emotional facilitation of memory has been attributed to the engagement of
      diffusely projecting neuromodulatory systems that enhance the consolidation of
      synaptic plasticity in regions activated by the experience. This process requires
      the propagation of signals between brain regions, and for those signals to induce
      long-lasting synaptic plasticity. Both of these demands are met by gamma
      oscillations, which reflect synchronous population activity on a fast timescale
      (35-120 Hz). Regions known to participate in the formation of emotional memories,
      such as the basolateral amygdala, also promote gamma-band activation throughout
      cortical and subcortical circuits. Recent studies have demonstrated that gamma
      oscillations are enhanced during emotional situations, coherent between regions
      engaged by salient stimuli, and predict subsequent memory for cues associated
      with aversive stimuli. Furthermore, neutral stimuli that come to predict
      emotional events develop enhanced gamma oscillations, reflecting altered
      processing in the brain, which may underpin how past emotional experiences color
      future learning and memory. 

PMID- 24319418
TI  - fMRI evidence for the interaction between orthography and phonology in reading
      Chinese compound words.
AB  - Compound words make up a major part of modern Chinese vocabulary. Behavioral
      studies have demonstrated that access to lexical semantics of compound words is
      driven by the interaction between orthographic and phonological information.
      However, little is known about the neural underpinnings of compound word
      processing. In this functional magnetic resonance imaging study, we asked
      participants to perform lexical decisions to pseudohomophones, which were
      constructed by replacing one or both constituents of two-character compound words
      with orthographically dissimilar homophonic characters. Mixed pseudohomophones,
      which shared the first constituent with the base words, were more difficult to
      reject than non-pseudohomophone non-words. This effect was accompanied by the
      increased activation of bilateral inferior frontal gyrus (IFG), left inferior
      parietal lobule (IPL), and left angular gyrus. The pure pseudohomophones, which
      shared no constituent with their base words, were rejected as quickly as non-word
      controls and did not elicit any significant neural activation. The effective
      connectivity of a phonological pathway from left IPL to left IFG was enhanced for
      the mixed pseudohomophones but not for pure pseudohomophones. These findings
      demonstrated that phonological activation alone, as in the case of the pure
      pseudohomophones, is not sufficient to drive access to lexical representations of
      compound words, and that orthographic information interacts with phonology,
      playing a gating role in the recognition of Chinese compound words. 

PMID- 24319419
TI  - BrainCAT - a tool for automated and combined functional magnetic resonance
      imaging and diffusion tensor imaging brain connectivity analysis.
AB  - Multimodal neuroimaging studies have recently become a trend in the neuroimaging
      field and are certainly a standard for the future. Brain connectivity studies
      combining functional activation patterns using resting-state or task-related
      functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)
      tractography have growing popularity. However, there is a scarcity of solutions
      to perform optimized, intuitive, and consistent multimodal fMRI/DTI studies. Here
      we propose a new tool, brain connectivity analysis tool (BrainCAT), for an
      automated and standard multimodal analysis of combined fMRI/DTI data, using
      freely available tools. With a friendly graphical user interface, BrainCAT aims
      to make data processing easier and faster, implementing a fully automated data
      processing pipeline and minimizing the need for user intervention, which
      hopefully will expand the use of combined fMRI/DTI studies. Its validity was
      tested in an aging study of the default mode network (DMN) white matter
      connectivity. The results evidenced the cingulum bundle as the structural
      connector of the precuneus/posterior cingulate cortex and the medial frontal
      cortex, regions of the DMN. Moreover, mean fractional anisotropy (FA) values
      along the cingulum extracted with BrainCAT showed a strong correlation with FA
      values from the manual selection of the same bundle. Taken together, these
      results provide evidence that BrainCAT is suitable for these analyses. 

PMID- 24319420
TI  - MEG masked priming evidence for form-based decomposition of irregular verbs.
AB  - To what extent does morphological structure play a role in early processing of
      visually presented English past tense verbs? Previous masked priming studies have
      demonstrated effects of obligatory form-based decomposition for genuinely affixed
      words (teacher-TEACH) and pseudo-affixed words (corner-CORN), but not for
      orthographic controls (brothel-BROTH). Additionally, MEG single word reading
      studies have demonstrated that the transition probability from stem to affix (in
      genuinely affixed words) modulates an early evoked response known as the M170;
      parallel findings have been shown for the transition probability from stem to
      pseudo-affix (in pseudo-affixed words). Here, utilizing the M170 as a neural
      index of visual form-based morphological decomposition, we ask whether the M170
      demonstrates masked morphological priming effects for irregular past tense verbs
      (following a previous study which obtained behavioral masked priming effects for
      irregulars). Dual mechanism theories of the English past tense predict a rule
      based decomposition for regulars but not for irregulars, while certain single
      mechanism theories predict rule-based decomposition even for irregulars. MEG data
      was recorded for 16 subjects performing a visual masked priming lexical decision
      task. Using a functional region of interest (fROI) defined on the basis of
      repetition priming and regular morphological priming effects within the left
      fusiform and inferior temporal regions, we found that activity in this fROI was
      modulated by the masked priming manipulation for irregular verbs, during the time
      window of the M170. We also found effects of the scores generated by the learning
      model of Albright and Hayes (2003) on the degree of priming for irregular verbs.
      The results favor a single mechanism account of the English past tense, in which
      even irregulars are decomposed into stems and affixes prior to lexical access, as
      opposed to a dual mechanism model, in which irregulars are recognized as whole
      forms. 

PMID- 24319421
TI  - Multisensory Integration in Non-Human Primates during a Sensory-Motor Task.
AB  - Daily our central nervous system receives inputs via several sensory modalities,
      processes them and integrates information in order to produce a suitable
      behavior. The amazing part is that such a multisensory integration brings all
      information into a unified percept. An approach to start investigating this
      property is to show that perception is better and faster when multimodal stimuli
      are used as compared to unimodal stimuli. This forms the first part of the
      present study conducted in a non-human primate's model (n = 2) engaged in a
      detection sensory-motor task where visual and auditory stimuli were displayed
      individually or simultaneously. The measured parameters were the reaction time
      (RT) between stimulus and onset of arm movement, successes and errors
      percentages, as well as the evolution as a function of time of these parameters
      with training. As expected, RTs were shorter when the subjects were exposed to
      combined stimuli. The gains for both subjects were around 20 and 40 ms, as
      compared with the auditory and visual stimulus alone, respectively. Moreover the
      number of correct responses increased in response to bimodal stimuli. We
      interpreted such multisensory advantage through redundant signal effect which
      decreases perceptual ambiguity, increases speed of stimulus detection, and
      improves performance accuracy. The second part of the study presents single-unit
      recordings derived from the premotor cortex (PM) of the same subjects during the
      sensory-motor task. Response patterns to sensory/multisensory stimulation are
      documented and specific type proportions are reported. Characterization of
      bimodal neurons indicates a mechanism of audio-visual integration possibly
      through a decrease of inhibition. Nevertheless the neural processing leading to
      faster motor response from PM as a polysensory association cortical area remains
      still unclear. 

PMID- 24319422
TI  - Resting state fMRI reveals a default mode dissociation between retrosplenial and
      medial prefrontal subnetworks in ASD despite motion scrubbing.
AB  - In resting state functional magnetic resonance imaging (fMRI) studies of autism
      spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is
      a persistent finding. However, the picture of the default mode network (DMN)
      hypoconnectivity remains incomplete. In addition, the functional connectivity
      analyses have been shown to be susceptible even to subtle motion. DMN
      hypoconnectivity in ASD has been specifically called for re-evaluation with
      stringent motion correction, which we aimed to conduct by so-called scrubbing. A
      rich set of default mode subnetworks can be obtained with high dimensional group
      independent component analysis (ICA) which can potentially provide more detailed
      view of the connectivity alterations. We compared the DMN connectivity in high
      functioning adolescents with ASDs to typically developing controls using ICA dual
      regression with decompositions from typical to high dimensionality. Dual
      regression analysis within DMN subnetworks did not reveal alterations but
      connectivity between anterior and posterior DMN subnetworks was decreased in ASD.
      The results were very similar with and without motion scrubbing thus indicating
      the efficacy of the conventional motion correction methods combined with ICA dual
      regression. Specific dissociation between DMN subnetworks was revealed on high
      ICA dimensionality, where networks centered at the medial prefrontal cortex and
      retrosplenial cortex showed weakened coupling in adolescents with ASDs compared
      to typically developing control participants. Generally the results speak for
      disruption in the anterior-posterior DMN interplay on the network level whereas
      local functional connectivity in DMN seems relatively unaltered. 

PMID- 24319423
TI  - Using environmental distractors in the diagnosis of ADHD.
AB  - This study examined the effect of the incorporation of environmental distractors
      in computerized continuous performance test (CPT) on the ability of the test in
      distinguishing ADHD from non-ADHD children. It was hypothesized that children
      with ADHD would display more distractibility than controls while performing CPT
      as measured by omission errors in the presence of pure visual, pure auditory, and
      a combination of visual and auditory distracting stimuli. Participants were 663
      children aged 7-12 years, of them 345 diagnosed with ADHD and 318 without ADHD.
      Results showed that ADHD children demonstrated more omission errors than their
      healthy peers in all CPT conditions (no distractors, pure visual or auditory
      distractors and combined distractors). However, ADHD and non-ADHD children
      differed in their reaction to distracting stimuli; while all types of distracting
      stimuli increased the rate of omission errors in ADHD children, only combined
      visual and auditory distractors increased it in non-ADHD children. Given the low
      ecological validity of many CPT, these findings suggest that incorporating
      distractors in CPT improves the ability to distinguish ADHD from non-ADHD
      children. 

PMID- 24319424
TI  - Information maximization principle explains the emergence of complex cell-like
      neurons.
AB  - We propose models and a method to qualitatively explain the receptive field
      properties of complex cells in the primary visual cortex. We apply a learning
      method based on the information maximization principle in a feedforward network,
      which comprises an input layer of image patches, simple cell-like first-output
      layer neurons, and second-output-layer neurons (Model 1). The information
      maximization results in the emergence of the complex cell-like receptive field
      properties in the second-output-layer neurons. After learning, second-output
      layer neurons receive connection weights having the same size from two first
      output-layer neurons with sign-inverted receptive fields. The second-output-layer
      neurons replicate the phase invariance and iso-orientation suppression.
      Furthermore, on the basis of these results, we examine a simplified model showing
      the emergence of complex cell-like receptive fields (Model 2). We show that after
      learning, the output neurons of this model exhibit iso-orientation suppression,
      cross-orientation facilitation, and end stopping, which are similar to those
      found in complex cells. These properties of model neurons suggest that complex
      cells in the primary visual cortex become selective to features composed of edges
      to increase the variability of the output. 

PMID- 24319425
TI  - Increased motor cortex excitability during motor imagery in brain-computer
      interface trained subjects.
AB  - BACKGROUND: Motor imagery (MI) is the mental performance of movement without
      muscle activity. It is generally accepted that MI and motor performance have
      similar physiological mechanisms. PURPOSE: To investigate the activity and
      excitability of cortical motor areas during MI in subjects who were previously
      trained with an MI-based brain-computer interface (BCI). SUBJECTS AND METHODS:
      Eleven healthy volunteers without neurological impairments (mean age, 36 years;
      range: 24-68 years) were either trained with an MI-based BCI (BCI-trained, n = 5)
      or received no BCI training (n = 6, controls). Subjects imagined grasping in a
      blocked paradigm task with alternating rest and task periods. For evaluating the
      activity and excitability of cortical motor areas we used functional MRI and
      navigated transcranial magnetic stimulation (nTMS). RESULTS: fMRI revealed
      activation in Brodmann areas 3 and 6, the cerebellum, and the thalamus during MI
      in all subjects. The primary motor cortex was activated only in BCI-trained
      subjects. The associative zones of activation were larger in non-trained
      subjects. During MI, motor evoked potentials recorded from two of the three
      targeted muscles were significantly higher only in BCI-trained subjects. The
      motor threshold decreased (median = 17%) during MI, which was also observed only
      in BCI-trained subjects. CONCLUSION: Previous BCI training increased motor cortex
      excitability during MI. These data may help to improve BCI applications,
      including rehabilitation of patients with cerebral palsy.

PMID- 24319427
TI  - Multi-atlas segmentation with joint label fusion and corrective learning-an open
      source implementation.
AB  - Label fusion based multi-atlas segmentation has proven to be one of the most
      competitive techniques for medical image segmentation. This technique transfers
      segmentations from expert-labeled images, called atlases, to a novel image using
      deformable image registration. Errors produced by label transfer are further
      reduced by label fusion that combines the results produced by all atlases into a
      consensus solution. Among the proposed label fusion strategies, weighted voting
      with spatially varying weight distributions derived from atlas-target intensity
      similarity is a simple and highly effective label fusion technique. However, one
      limitation of most weighted voting methods is that the weights are computed
      independently for each atlas, without taking into account the fact that different
      atlases may produce similar label errors. To address this problem, we recently
      developed the joint label fusion technique and the corrective learning technique,
      which won the first place of the 2012 MICCAI Multi-Atlas Labeling Challenge and
      was one of the top performers in 2013 MICCAI Segmentation: Algorithms, Theory and
      Applications (SATA) challenge. To make our techniques more accessible to the
      scientific research community, we describe an Insight-Toolkit based open source
      implementation of our label fusion methods. Our implementation extends our
      methods to work with multi-modality imaging data and is more suitable for
      segmentation problems with multiple labels. We demonstrate the usage of our tools
      through applying them to the 2012 MICCAI Multi-Atlas Labeling Challenge brain
      image dataset and the 2013 SATA challenge canine leg image dataset. We report the
      best results on these two datasets so far. 

PMID- 24319426
TI  - Defining nodes in complex brain networks.
AB  - Network science holds great promise for expanding our understanding of the human
      brain in health, disease, development, and aging. Network analyses are quickly
      becoming the method of choice for analyzing functional MRI data. However, many
      technical issues have yet to be confronted in order to optimize results. One
      particular issue that remains controversial in functional brain network analyses
      is the definition of a network node. In functional brain networks a node
      represents some predefined collection of brain tissue, and an edge measures the
      functional connectivity between pairs of nodes. The characteristics of a node,
      chosen by the researcher, vary considerably in the literature. This manuscript
      reviews the current state of the art based on published manuscripts and
      highlights the strengths and weaknesses of three main methods for defining nodes.
      Voxel-wise networks are constructed by assigning a node to each, equally sized
      brain area (voxel). The fMRI time-series recorded from each voxel is then used to
      create the functional network. Anatomical methods utilize atlases to define the
      nodes based on brain structure. The fMRI time-series from all voxels within the
      anatomical area are averaged and subsequently used to generate the network.
      Functional activation methods rely on data from traditional fMRI activation
      studies, often from databases, to identify network nodes. Such methods identify
      the peaks or centers of mass from activation maps to determine the location of
      the nodes. Small (~10-20 millimeter diameter) spheres located at the coordinates
      of the activation foci are then applied to the data being used in the network
      analysis. The fMRI time-series from all voxels in the sphere are then averaged,
      and the resultant time series is used to generate the network. We attempt to
      clarify the discussion and move the study of complex brain networks forward.
      While the "correct" method to be used remains an open, possibly unsolvable
      question that deserves extensive debate and research, we argue that the best
      method available at the current time is the voxel-wise method. 

PMID- 24319428
TI  - Cognitive Inconsistency and Practice-Related Learning in Older Adults.
AB  - The current study examined predictors of individual differences in the magnitude
      of practice-related improvements achieved by 87 older adults (meanage 63.52
      years) over 18-weeks of cognitive practice. Cognitive inconsistency in both
      baseline trial-to-trial reaction times and week-to-week accuracy scores was
      included as predictors of practice-related gains in two measures of processing
      speed. Conditional growth models revealed that both reaction time and accuracy
      level and rate-of-change in functioning were related to inconsistency, even after
      controlling for mean-level, but that increased inconsistency was negatively
      associated with accuracy versus positively associated with reaction time
      improvement. Cognitive inconsistency may signal dysregulation in the ability to
      control cognitive performance or may be indicative of adaptive attempts at
      functioning.

PMID- 24319429
TI  - Immunotherapy targeting cytokines in neuropathic pain.

PMID- 24319430
TI  - The use of lipid-based nanocarriers for targeted pain therapies.
AB  - Sustained delivery of analgesic agents at target sites remains a critical issue
      for effective pain management. The use of nanocarriers has been reported to
      facilitate effective delivery of these agents to target sites while minimizing
      systemic toxicity. These include the use of biodegradable liposomal or polymeric
      carriers. Of these, liposomes present as an attractive delivery system due to
      their flexible physicochemical properties which allow easy manipulation in order
      to address different delivery considerations. Their favorable toxicity profiles
      and ease of large scale production also make their clinical use feasible. In this
      review, we will discuss the concept of using liposomes as a drug delivery
      carrier, their in vitro characteristics as well as in vivo behavior. Current
      advances in the targeted liposomal delivery of analgesic agents and their impacts
      on the field of pain management will be presented. 

PMID- 24319434
TI  - Getting into the musical zone: trait emotional intelligence and amount of
      practice predict flow in pianists.
AB  - Being "in flow" or "in the zone" is defined as an extremely focused state of
      consciousness which occurs during intense engagement in an activity. In general,
      flow has been linked to peak performances (high achievement) and feelings of
      intense pleasure and happiness. However, empirical research on flow in music
      performance is scarce, although it may offer novel insights into the question of
      why musicians engage in musical activities for extensive periods of time. Here,
      we focused on individual differences in a group of 76 piano performance students
      and assessed their flow experience in piano performance as well as their trait
      emotional intelligence. Multiple regression analysis revealed that flow was
      predicted by the amount of daily practice and trait emotional intelligence. Other
      background variables (gender, age, duration of piano training and age of first
      piano training) were not predictive. To predict high achievement in piano
      performance (i.e., winning a prize in a piano competition), a seven-predictor
      logistic regression model was fitted to the data, and we found that the odds of
      winning a prize in a piano competition were predicted by the amount of daily
      practice and the age at which piano training began. Interestingly, a positive
      relationship between flow and high achievement was not supported. Further, we
      explored the role of musical emotions and musical styles in the induction of flow
      by a self-developed questionnaire. Results suggest that besides individual
      differences among pianists, specific structural and compositional features of
      musical pieces and related emotional expressions may facilitate flow experiences.
      Altogether, these findings highlight the role of emotion in the experience of
      flow during music performance and call for further experiments addressing emotion
      in relation to the performer and the music alike. 

PMID- 24319433
TI  - Similar and different gray matter deficits in schizophrenia patients and their
      unaffected biological relatives.
AB  - Neuroimaging studies have revealed significant reductions in the gray matter (GM)
      of several brain regions in patients with schizophrenia, a neuropsychiatric
      disorder with high hereditability. However, it is unclear whether unaffected
      relatives have GM abnormalities in common with their affected relatives, which
      may relate to susceptibility to developing schizophrenia. To address this issue,
      we conducted two separate meta-analyses of voxel-based morphometry to investigate
      GM abnormalities in schizophrenia patients and their unaffected relatives. One
      meta-analysis compared a patient group with healthy controls, whereas the other
      meta-analysis compared the unaffected relatives with healthy controls. Eight
      studies comprising 495 patients with schizophrenia, 584 unaffected relatives of
      patients, and 596 healthy controls were systematically included in the present
      study. Compared to healthy controls, the patient group showed decreased GM in the
      right cuneus, the right superior frontal gyrus, the right insula and the left
      claustrum, and increased GM in the bilateral putamen, the right parahippocampal
      gyrus, the left precentral gyrus, the left inferior temporal gyri, and the right
      cerebellar tonsil. The comparison between unaffected relatives and healthy
      controls showed a GM reduction in the left claustrum, the bilateral
      parahippocampal gyri, the left fusiform gyrus, the right inferior temporal gyrus,
      and the bilateral medial prefrontal cortices, whereas increased GM was observed
      in the right hippocampus, the right fusiform gyrus, the right precentral gyrus,
      and the right precuneus. Thus, our meta-analyses show that the GM changes in
      schizophrenia patients and their unaffected relatives are largely different,
      although there is subtle overlap in some regions. 

PMID- 24319432
TI  - Peroxisome deficient invertebrate and vertebrate animal models.
AB  - Although peroxisomes are ubiquitous organelles in all animal species, their
      importance for the functioning of tissues and organs remains largely unresolved.
      Because peroxins are essential for the biogenesis of peroxisomes, an obvious
      approach to investigate their physiological role is to inactivate a Pex gene or
      to suppress its translation. This has been performed in mice but also in more
      primitive organisms including D. melanogaster, C. elegans, and D. rerio, and the
      major findings and abnormalities in these models will be highlighted. Although
      peroxisomes are generally not essential for embryonic development and
      organogenesis, a generalized inactivity of peroxisomes affects lifespan and
      posthatching/postnatal growth, proving that peroxisomal metabolism is necessary
      for the normal maturation of these organisms. Strikingly, despite the wide
      variety of model organisms, corresponding tissues are affected including the
      central nervous system and the testis. By inactivating peroxisomes in a cell type
      selective way in the brain of mice, it was also demonstrated that peroxisomes are
      necessary to prevent neurodegeneration. As these peroxisome deficient model
      organisms recapitulate pathologies of patients affected with peroxisomal
      diseases, their further analysis will contribute to the elucidation of still
      elusive pathogenic mechanisms. 

PMID- 24319435
TI  - Flexibility of orthographic and graphomotor coordination during a handwritten
      copy task: effect of time pressure.
AB  - The coordination of the various processes involved in language production is a
      subject of keen debate in writing research. Some authors hold that writing
      processes can be flexibly coordinated according to task demands, whereas others
      claim that process coordination is entirely inflexible. For instance,
      orthographic planning has been shown to be resource-dependent during handwriting,
      but inflexible in typing, even under time pressure. The present study therefore
      went one step further in studying flexibility in the coordination of orthographic
      processing and graphomotor execution, by measuring the impact of time pressure
      during a handwritten copy task. Orthographic and graphomotor processes were
      observed via syllable processing. Writers copied out two- and three-syllable
      words three times in a row, with and without time pressure. Latencies and letter
      measures at syllable boundaries were analyzed. We hypothesized that if
      coordination is flexible and varies according to task demands, it should be
      modified by time pressure, affecting both latency before execution and duration
      of execution. We therefore predicted that the extent of syllable processing
      before execution would be reduced under time pressure and, as a consequence,
      syllable effects during execution would be more salient. Results showed, however,
      that time pressure interacted neither with syllable number nor with syllable
      structure. Accordingly, syllable processing appears to remain the same regardless
      of time pressure. The flexibility of process coordination during handwriting is
      discussed, as is the operationalization of time pressure constraints. 

PMID- 24319436
TI  - Quantized visual awareness.
AB  - The proposed model holds that, at its most fundamental level, visual awareness is
      quantized. That is to say that visual awareness arises as individual bits of
      awareness through the action of neural circuits with hundreds to thousands of
      neurons in at least the human striate cortex. Circuits with specific topologies
      will reproducibly result in visual awareness that correspond to basic aspects of
      vision like color, motion, and depth. These quanta of awareness (qualia) are
      produced by the feedforward sweep that occurs through the geniculocortical
      pathway but are not integrated into a conscious experience until recurrent
      processing from centers like V4 or V5 select the appropriate qualia being
      produced in V1 to create a percept. The model proposed here has the potential to
      shift the focus of the search for visual awareness to the level of microcircuits
      and these likely exist across the kingdom Animalia. Thus establishing qualia as
      the fundamental nature of visual awareness will not only provide a deeper
      understanding of awareness, but also allow for a more quantitative understanding
      of the evolution of visual awareness throughout the animal kingdom. 

PMID- 24319431
TI  - Mechanisms of antidepressant resistance.
AB  - Depression is one of the most frequent and severe mental disorder. Since the
      discovery of antidepressant (AD) properties of the imipramine and then after of
      other tricyclic compounds, several classes of psychotropic drugs have shown be
      effective in treating major depressive disorder (MDD). However, there is a wide
      range of variability in response to ADs that might lead to non response or
      partial response or in increased rate of relapse or recurrence. The mechanisms of
      response to AD therapy are poorly understood, and few biomarkers are available
      than can predict response to pharmacotherapy. Here, we will first review markers
      that can be used to predict response to pharmacotherapy, such as markers of drug
      metabolism or blood-brain barrier (BBB) function, the activity of specific brain
      areas or neurotransmitter systems, hormonal dysregulations or plasticity, and
      related molecular targets. We will describe both clinical and preclinical studies
      and describe factors that might affect the expression of these markers, including
      environmental or genetic factors and comorbidities. This information will permit
      us to suggest practical recommendations and innovative treatment strategies to
      improve therapeutic outcomes. 

PMID- 24319437
TI  - Can enlightenment be traced to specific neural correlates, cognition, or
      behavior? No, and (a qualified) Yes.

PMID- 24319438
TI  - Song and speech: examining the link between singing talent and speech imitation
      ability.
AB  - In previous research on speech imitation, musicality, and an ability to sing were
      isolated as the strongest indicators of good pronunciation skills in foreign
      languages. We, therefore, wanted to take a closer look at the nature of the
      ability to sing, which shares a common ground with the ability to imitate speech.
      This study focuses on whether good singing performance predicts good speech
      imitation. Forty-one singers of different levels of proficiency were selected for
      the study and their ability to sing, to imitate speech, their musical talent and
      working memory were tested. Results indicated that singing performance is a
      better indicator of the ability to imitate speech than the playing of a musical
      instrument. A multiple regression revealed that 64% of the speech imitation score
      variance could be explained by working memory together with educational
      background and singing performance. A second multiple regression showed that 66%
      of the speech imitation variance of completely unintelligible and unfamiliar
      language stimuli (Hindi) could be explained by working memory together with a
      singer's sense of rhythm and quality of voice. This supports the idea that both
      vocal behaviors have a common grounding in terms of vocal and motor flexibility,
      ontogenetic and phylogenetic development, neural orchestration and auditory
      memory with singing fitting better into the category of "speech" on the
      productive level and "music" on the acoustic level. As a result, good singers
      benefit from vocal and motor flexibility, productively and cognitively, in three
      ways. (1) Motor flexibility and the ability to sing improve language and musical
      function. (2) Good singers retain a certain plasticity and are open to new and
      unusual sound combinations during adulthood both perceptually and productively.
      (3) The ability to sing improves the memory span of the auditory working memory. 

PMID- 24319439
TI  - Conjoint measurement of disorder prevalence, test sensitivity, and test
      specificity: notes on Botella, Huang, and Suero's multinomial model.

PMID- 24319440
TI  - Response inhibition is modulated by functional cerebral asymmetries for facial
      expression perception.
AB  - The efficacy of executive functions is critically modulated by information
      processing in earlier cognitive stages. For example, initial processing of verbal
      stimuli in the language-dominant left-hemisphere leads to more efficient response
      inhibition than initial processing of verbal stimuli in the non-dominant right
      hemisphere. However, it is unclear whether this organizational principle is
      specific for the language system, or a general principle that also applies to
      other types of lateralized cognition. To answer this question, we investigated
      the neurophysiological correlates of early attentional processes, facial
      expression perception and response inhibition during tachistoscopic presentation
      of facial "Go" and "Nogo" stimuli in the left and the right visual field (RVF).
      Participants committed fewer false alarms after Nogo-stimulus presentation in the
      left compared to the RVF. This right-hemispheric asymmetry on the behavioral
      level was also reflected in the neurophysiological correlates of face perception,
      specifically in a right-sided asymmetry in the N170 amplitude. Moreover, the
      right-hemispheric dominance for facial expression processing also affected event
      related potentials typically related to response inhibition, namely the Nogo-N2
      and Nogo-P3. These findings show that an effect of hemispheric asymmetries in
      early information processing on the efficacy of higher cognitive functions is not
      limited to left-hemispheric language functions, but can be generalized to
      predominantly right-hemispheric functions. 

PMID- 24319441
TI  - Basic fibroblast growth factor predicts cardiovascular disease occurrence in
      participants from the veterans affairs diabetes trial.
AB  - AIM: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality
      in adults with type 2 diabetes mellitus. The aim of the present study was to test
      whether plasma basic fibroblast growth factor (bFGF) levels predict future CVD
      occurrence in adults from the Veterans Affairs Diabetes Trial (VADT). METHODS:
      Nearly 400 veterans, 40 years of age or older having a mean baseline diabetes
      duration of 11.4 years were recruited from outpatient clinics at six
      geographically distributed sites in the VADT. Within the VADT, they were randomly
      assigned to intensive or standard glycemic treatment, with follow-up as much as
      seven and one-half years. CVD occurrence was examined at baseline in the patient
      population and during randomized treatment. Plasma bFGF was determined with a
      sensitive, specific two-site enzyme-linked immunoassay at the baseline study
      visit in all 399 subjects and repeated at the year 1 study visit in a randomly
      selected subset of 215 subjects. RESULTS: One hundred and five first
      cardiovascular events occurred in these 399 subjects. The best fit model of risk
      factors associated with the time to first CVD occurrence (in the study) over a
      seven and one-half year period had as significant predictors: prior
      cardiovascular event [hazard ratio (HR) 3.378; 95% confidence intervals (CI)
      3.079-3.807; P < 0.0001), baseline plasma bFGF (HR 1.008; 95% CI 1.002-1.014; P =
      0.01), age (HR 1.027; 95% CI 1.004-1.051; P = 0.019), baseline plasma
      triglycerides (HR 1.001; 95% CI 1.000-1.002; P = 0.02), and diabetes duration
      treatment interaction (P = 0.03). Intensive glucose-lowering was associated with
      significantly decreased hazard ratios for CVD occurrence (0.38-0.63) in patients
      with known diabetes duration of 0-10 years, and non-significantly increased
      hazard ratios for CVD occurrence (0.82-1.78) in patients with longer diabetes
      duration. CONCLUSION: High level of plasma bFGF is a predictive biomarker of
      future CVD occurrence in this population of adult type 2 diabetes.

PMID- 24319442
TI  - Food environments select microorganisms based on selfish energetic behavior.
AB  - Nutrient richness, and specifically the abundance of mono- and disaccharides that
      characterize several food matrixes, such as milk and grape juice, has allowed the
      speciation of lactic acid bacteria and yeasts with a high fermentation capacity
      instead of energetically favorable respiratory metabolism. In these environmental
      contexts, rapid sugar consumption and lactic acid or ethanol production,
      accumulation, and tolerance, together with the ability to propagate in the
      absence of oxygen, are several of the "winning" traits that have apparently
      evolved and become specialized to perfection in these fermenting microorganisms.
      Here, we summarize and discuss the evolutionary context that has driven energetic
      metabolism in food-associated microorganisms, using the dairy species Lactococcus
      lactis and Streptococcus thermophilus among prokaryotes and the bakers' yeast
      Saccharomyces cerevisiae among eukaryotes as model organisms. 

PMID- 24319444
TI  - Natural Killer Cells in Afferent Lymph Express an Activated Phenotype and Readily
      Produce IFN-gamma.
AB  - Natural killer (NK) cells are motile cells that migrate between peripheral blood
      (PB), lymph nodes (LNs), and various organs. Domestic animals have frequently
      been used to study cellular migration, and offer unique opportunities for such
      studies. The aim of this study was to characterize the phenotype and cytokine
      producing capacity of NK cells in bovine skin-draining lymph. NKp46/NCR1(+) CD3(
      ) cells constituted 2-11% of mononuclear cells in afferent lymph (AL), a majority
      of cells were CD16(+), CD8alpha(+), and CD2(-/low), and elevated CD25 and CD44
      expression indicated an activated phenotype. Interestingly, significantly fewer
      AL NK cells expressed the early activation marker CD69 compared to PB NK cells. A
      large proportion of lymph and blood NK cells produced interferon (IFN)-gamma
      following stimulation with IL-2 and IL-12. Notably, in AL, but not blood, a
      similar amount of IFN-gamma(+) NK cells was observed when cells were stimulated
      with IL-12 alone. Overall, AL NK cells were more similar to LN-residing NK cells
      than those circulating in PB. We conclude that AL appears to be an important
      migration route for tissue-activated NK cells, and may represent an alternative
      route for NK cell traffic to LNs. These findings may have important implications
      in the development of adjuvant strategies that aim to target NK cells in a
      vaccine response. 

PMID- 24319443
TI  - Strict Major Histocompatibility Complex Molecule Class-Specific Binding by Co
      Receptors Enforces MHC-Restricted alphabeta TCR Recognition during T Lineage
      Subset Commitment.
AB  - Since the discovery of co-receptor dependent alphabetaTCR recognition,
      considerable effort has been spent on elucidating the basis of CD4 and CD8
      lineage commitment in the thymus. The latter is responsible for generating mature
      CD4 helper and CD8alphabeta cytotoxic T cell subsets. Although CD4(+) and CD8(+)
      T cell recognition of peptide antigens is known to be MHC class II- and MHC class
      I-restricted, respectively, the mechanism of single positive (SP) thymocyte
      lineage commitment from bipotential double-positive (DP) progenitors is not fully
      elucidated. Classical models to explain thymic CD4 vs. CD8 fate determination
      have included a stochastic selection model or instructional models. The latter
      are based either on strength of signal or duration of signal impacting fate. More
      recently, differential co-receptor gene imprinting has been shown to be involved
      in expression of transcription factors impacting cytotoxic T cell development.
      Here, we address commitment from a structural perspective, focusing on the nature
      of co-receptor binding to MHC molecules. By surveying 58 MHC class II and 224 MHC
      class I crystal structures in the Protein Data Bank, it becomes clear that CD4
      cannot bind to MHC I molecules, nor can CD8alphabeta or CD8alphaalpha bind to MHC
      II molecules. Given that the co-receptor delivers Lck to phosphorylate exposed
      CD3 ITAMs within a peptide/MHC (pMHC)-ligated TCR complex to initiate cell
      signaling, this strict co-receptor recognition fosters MHC class-restricted SP
      thymocyte lineage commitment at the DP stage even though both co-receptors are
      expressed on a single cell. In short, the binding preference of an alphabetaTCR
      for a peptide complexed with an MHC molecule dictates which co-receptor
      subsequently binds, thereby supporting development of that subset lineage. How
      function within the lineage is linked further to biopotential fate determination
      is discussed. 

PMID- 24319445
TI  - NLRC5, at the Heart of Antigen Presentation.
AB  - Nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs) are
      intracellular proteins mainly involved in pathogen recognition, inflammatory
      responses, and cell death. Until recently, the function of the family member NLR
      caspase recruitment domain (CARD) containing 5 (NLRC5) has been a matter of
      debate. It is now clear that NLRC5 acts as a transcriptional regulator of the
      major-histocompatibility complex class I. In this review we detail the
      development of our understanding of NLRC5 function, discussing both the accepted
      and the controversial aspects of NLRC5 activity. We give insight into the
      molecular mechanisms, and the potential implications, of NLRC5 function in health
      and disease. 

PMID- 24319446
TI  - Mechanisms of sterile inflammation.

PMID- 24319447
TI  - An updated view of the intracellular mechanisms regulating cross-presentation.
AB  - Cross-presentation involves the presentation of peptides derived from
      internalized cargo on major histocompatibility complex class I molecules by
      dendritic cells, a process critical for tolerance and immunity. Detailed studies
      of the pathways mediating cross-presentation have revealed that this process
      takes place in a specialized subcellular compartment with a unique set of
      proteins. In this review, we focus on the recently appreciated role for
      intracellular vesicular traffic, which serves to equip compartments such as
      endosomes and phagosomes with the necessary apparatus for conducting the various
      steps of cross-presentation. We also consider how these pathways may integrate
      with inflammatory signals particularly from pattern recognition receptors that
      detect the presence of microbial components during infection. We discuss the
      consequences of such signals on initiating cross-presentation to stimulate
      adaptive CD8 T cell responses. 

PMID- 24319448
TI  - Type III chaperones & Co in bacterial plant pathogens: a set of specialized
      bodyguards mediating effector delivery.
AB  - Gram-negative plant pathogenic bacteria possess a type III secretion system
      (T3SS) to inject bacterial proteins, called type III effectors (T3Es), into host
      cells through a specialized syringe structure. T3Es are virulence factors that
      can suppress plant immunity but they can also conversely be recognized by the
      plant and trigger specific resistance mechanisms. The T3SS and injected T3Es play
      a central role in determining the outcome of a host-pathogen interaction. Still
      little is known in plant pathogens on the assembly of the T3SS and the regulatory
      mechanisms involved in the temporal control of its biosynthesis and T3E
      translocation. However, recent insights point out the role of several proteins as
      prime candidates in the role of regulators of the type III secretion (T3S)
      process. In this review we report on the most recent advances on the regulation
      of the T3S by focusing on protein players involved in secretion/translocation
      regulations, including type III chaperones (T3Cs), type III secretion substrate
      specificity switch (T3S4) proteins and other T3S orchestrators. 

PMID- 24319450
TI  - Implications of the lack of desiccation tolerance in recalcitrant seeds.
AB  - A suite of interacting processes and mechanisms enables tolerance of desiccation
      and storage (conservation) of orthodox seeds in the dry state. While this is a
      long-term option under optimized conditions, dry orthodox seeds are not immortal,
      with life spans having been characterized as short, intermediate and long.
      Factors facilitating desiccation tolerance are metabolic "switch-off" and
      intracellular dedifferentiation. Recalcitrant seeds lack these mechanisms,
      contributing significantly to their desiccation sensitivity. Consequently,
      recalcitrant seeds, which are shed at high water contents, can be stored only in
      the short-term, under conditions not allowing dehydration. The periods of such
      hydrated storage are constrained by germination that occurs without the need for
      extraneous water, and the proliferation of seed-associated fungi.
      Cryopreservation is viewed as the only option for long-term conservation of the
      germplasm of recalcitrant-seeded species. This is not easily achieved, as each of
      the necessary procedures imposes oxidative damage. Intact recalcitrant seeds
      cannot be cryopreserved, the common practice being to use excised embryos or
      embryonic axes as explants. Dehydration is a necessary procedure prior to
      exposure to cryogenic temperatures, but this is associated with metabolism-linked
      injury mediated by uncontrolled reactive oxygen species generation and failing
      anti-oxidant systems. While the extent to which this occurs can be curtailed by
      maximizing drying rate (flash drying) it cannot be completely obviated. Explant
      cooling for, and rewarming after, cryostorage must necessarily be rapid, to avoid
      ice crystallization. The ramifications of desiccation sensitivity are discussed,
      as are problems involved in cryostorage, particularly those accompanying
      dehydration and damage consequent upon ice crystallization. While desiccation
      sensitivity is a "fact" of seed recalcitrance, resolutions of the difficulties
      involved germplasm conservation are possible as discussed. 

PMID- 24319449
TI  - Plastid thioredoxins: a "one-for-all" redox-signaling system in plants.
AB  - The sessile nature of plants forces them to face an ever-changing environment
      instead of escape from hostile conditions as animals do. In order to overcome
      this survival challenge, a fine monitoring and controlling of the status of the
      photosynthetic electron transport chain and the general metabolism is vital for
      these organisms. Frequently, evolutionary plant adaptation has consisted in the
      appearance of multigenic families, comprising an array of enzymes, structural
      components, or sensing, and signaling elements, in numerous occasions with highly
      conserved primary sequences that sometimes make it difficult to discern between
      redundancy and specificity among the members of a same family. However, all this
      gene diversity is aimed to sort environment-derived plant signals to efficiently
      channel the external incoming information inducing a right physiological answer.
      Oxygenic photosynthesis is a powerful source of reactive oxygen species (ROS),
      molecules with a dual oxidative/signaling nature. In response to ROS, one of the
      most frequent post-translational modifications occurring in redox signaling
      proteins is the formation of disulfide bridges (from Cys oxidation). This review
      is focused on the role of plastid thioredoxins (pTRXs), proteins containing two
      Cys in their active site and largely known as part of the plant redox-signaling
      network. Several pTRXs types have been described so far, namely, TRX f, m, x, y,
      and z. In recent years, improvements in proteomic techniques and the study of
      loss-of-function mutants have enabled us to grasp the importance of TRXs for the
      plastid physiology. We will analyze the specific signaling function of each TRX
      type and discuss about the emerging role in non-photosynthetic plastids of these
      redox switchers. 

PMID- 24319451
TI  - Nuclear components and dynamics during plant innate immunity.

PMID- 24319452
TI  - LEPREL1 Expression in Human Hepatocellular Carcinoma and Its Suppressor Role on
      Cell Proliferation.
AB  - Background. Hepatocellular carcinoma (HCC) is one of the most aggressive
      malignancies worldwide. It is characterized by its high invasive and metastatic
      potential. Leprecan-like 1 (LEPREL1) has been demonstrated to be downregulated in
      the HCC tissues in previous proteomics studies. The present study is aimed at a
      new understanding of LEPREL1 function in HCC. Methods. Quantitative RT-PCR,
      immunohistochemical analysis, and western blot analysis were used to evaluate the
      expression of LEPREL1 between the paired HCC tumor and nontumorous tissues. The
      biology function of LEPREL1 was investigated by Cell Counting Kit-8 (CCK8) assay
      and colony formation assay in HepG2 and Bel-7402 cells. Results. The levels of
      LEPREL1 mRNA and protein were significantly lower in the HCC tissues as compared
      to those of the nontumorous tissues. Reduced LEPREL1 expression was not
      associated with conventional clinical parameters of HCC. Overexpression of
      LEPREL1 in HepG2 and Bel-7402 cells inhibited cell proliferation (P < 0.01) and
      colony formation (P < 0.05). LEPREL1 suppressed tumor cell proliferation through
      regulation of the cell cycle by downregulation of cyclins. Conclusions. Clinical
      parameters analysis suggested that LEPREL1 was an independent factor in the
      development of HCC. The biology function experiments showed that LEPREL1 might
      serve as a potential tumor suppressor gene by inhibiting the HCC cell
      proliferation. 

PMID- 24319453
TI  - Immunochemical fecal occult blood test for detection of advanced colonic adenomas
      and colorectal cancer: comparison with colonoscopy results.
AB  - Background. Fecal immunochemical tests (FITs) have been used for colorectal
      cancer (CRC) screening in several countries. There is lack of information
      concerning diagnostic performances of this method in Brazil. Methods. Patients
      scheduled for elective colonoscopy provided one stool sample one week before
      colonoscopy. The accuracy of a qualitative FIT for detection of CRC and advanced
      adenomas was determined. Results. Overall 302 patients completed the study. Among
      them, 53.5% were high risk patients referred for screening or surveillance. Nine
      (3%) CRCs and 11 (3.6%) advanced adenomas were detected by colonoscopy.
      Sensitivity and specificity for CRC were, respectively, 88.9% and 87.6%. For
      advanced adenomas, sensitivity was 63.6% and specificity 87.6%. Conclusion. Our
      results showed good sensitivity and specificity of the FIT for detecting advanced
      neoplasias. This method may be a valuable tool for future screening programs in
      Brazil. 

PMID- 24319454
TI  - Effect of exercise on metabolic syndrome variables in breast cancer survivors.
AB  - Objective. Breast cancer survivors are highly sedentary, overweight, or obese,
      which puts them at increased risk for comorbid chronic disease. We examined the
      prevalence of, and changes in, metabolic syndrome following 6 months of an
      aerobic exercise versus usual care intervention in a sample of sedentary
      postmenopausal breast cancer survivors. Design and Methods. 65 participants were
      randomized to an aerobic exercise intervention (EX) (n = 35) mean BMI 30.8 (+/
      5.9) kg/m(2) or usual care (UC) (n = 30) mean BMI 29.4 (+/-7.4) kg/m(2).
      Metabolic syndrome prevalence was determined, as well as change in criteria and
      overall metabolic syndrome. Results. At baseline, 55.4% of total women met the
      criteria for metabolic syndrome. There was no statistically significant change in
      metabolic syndrome when comparing EX and UC. However, adhering to the exercise
      intervention (at least 120 mins/week of exercise) resulted in a significant (P =
      .009) decrease in metabolic syndrome z-score from baseline to 6 months (-0.76 +/-
      0.36) when compared to those who did not adhere (0.80 +/- 0.42). Conclusions. Due
      to a higher prevalence of metabolic syndrome in breast cancer survivors,
      lifestyle interventions are needed to prevent chronic diseases associated with
      obesity. Increasing exercise adherence is a necessary target for further research
      in obese breast cancer survivors. 

PMID- 24319455
TI  - Glucose Fluctuations during Gestation: An Additional Tool for Monitoring
      Pregnancy Complicated by Diabetes.
AB  - Continuous glucose monitoring (CGM) gives a unique insight into magnitude and
      duration of daily glucose fluctuations. Limited data are available on glucose
      variability (GV) in pregnancy. We aimed to assess GV in healthy pregnant women
      and cases of type 1 diabetes mellitus or gestational diabetes (GDM) and its
      possible association with HbA1c. CGM was performed in 50 pregnant women (20 type
      1, 20 GDM, and 10 healthy controls) in all three trimesters of pregnancy. We
      calculated mean amplitude of glycemic excursions (MAGE), standard deviation (SD),
      interquartile range (IQR), and continuous overlapping net glycemic action
      (CONGA), as parameters of GV. The high blood glycemic index (HBGI) and low blood
      glycemic index (LBGI) were also measured as indicators of hyperhypoglycemic risk.
      Women with type 1 diabetes showed higher GV, with a 2-fold higher risk of
      hyperglycemic spikes during the day, than healthy pregnant women or GDM ones. GDM
      women had only slightly higher GV parameters than healthy controls. HbA1c did not
      correlate with GV indicators in type 1 diabetes or GDM pregnancies. We provided
      new evidence of the importance of certain GV indicators in pregnant women with
      GDM or type 1 diabetes and recommended the use of CGM specifically in these
      populations. 

PMID- 24319456
TI  - A Two-Pathway Mathematical Model of the LH Response to GnRH that Predicts Self
      Priming.
AB  - An acute response of LH to a stimulatory pulse of GnRH is modelled as a result of
      a pathway (Pathway I) that consists of two compartments including a single (rate
      limiting) intermediate. In addition, a second pathway (Pathway II) was added,
      consisting of an intermediate transcription factor and subsequently a synthesised
      protein. Pathway II had a delayed effect on LH release due to the time taken to
      produce the intermediate protein. The model included synergism between these two
      pathways, which yielded an augmented response. The model accounts for a number of
      observations, including GnRH self-priming and the biphasic pattern of LH
      response. The same model was used to fit the data of the LH response when
      gonadotrophs responded to the addition of oxytocin in the response with a
      shoulder on the profile. Pathway I is able to be conceptualised as the basic
      Ca(2+)-mediated pathway. Pathway II contains features characteristic of the cAMP
      mediated pathway. Thus, we have provided an explanation for details of the nature
      of the profile of LH secretion and additionally enabled incorporation of cAMP in
      an integrating model. The study investigated the possibility of two interacting
      pathways being at the basis of both the shoulder on the LH surges and self
      priming, and the model illustrates that this appears to be highly likely. 

PMID- 24319457
TI  - Does Q223R Polymorphism of Leptin Receptor Influence on Anthropometric Parameters
      and Bone Density in Childhood Cancer Survivors?
AB  - Childhood cancer survivors are in augmented risk for developing obesity. For many
      factors leptin and leptin receptor gene polymorphism play an important role in
      the development and metabolism not only of fat, but also, bone tissue. The aim of
      the analysis was to find the relationships between Q223R, leptin levels, and
      anthropometric parameters. Patients and Methods. In the study 74 cancer survivors
      participated (ALL n = 64, lymphomas n = 10), and the control group consisted of
      51 healthy peers. Leptin blood concentration was determined by ELISA method. To
      estimate leptin receptor gene polymorphism, RFLP method was used. Bone mineral
      density (BMD) and content (BMC), fat, and lean tissue measurements were obtained
      by DXA. Results. We found no correlations between serum leptin concentrations and
      anthropometric parameters nor BMD. Serum leptin concentrations were significantly
      lower in the group of cancer survivors compared to controls; however, in those
      overweight from examined group we found leptin levels higher than those in
      nonoverweight. Genotype Q223R was not associated with higher leptin levels, BMI,
      BMD, body fat or lean tissue. Conclusion. To our knowledge, this is the first
      report describing the relationship between BMD and Q223R polymorphism in
      childhood cancer survivors. Further analysis, based on a larger group of
      patients, is needed to confirm these findings. 

PMID- 24319458
TI  - Gastroduodenal outlet obstruction and palliative self-expandable metal stenting:
      a dual-centre experience.
AB  - Background. Self-expandable metal stents (SEMs) are increasingly being utilised
      instead of invasive surgery for the palliation of patients with malignant
      gastroduodenal outlet obstruction. Aim. To review two tertiary centres'
      experience with placement of SEMs and clinical outcomes. Methods. Retrospective
      analysis of prospectively collected data over 12 years. Results. Ninety-four
      patients (mean age, 68; range 28-93 years) underwent enteral stenting during this
      period. The primary tumour was gastric adenocarcinoma in 27 (29%) patients,
      pancreatic adenocarcinoma in 45 (48%), primary duodenal adenocarcinoma in 8 (9%),
      and cholangiocarcinoma and other metastatic cancers in 14 (16%). A stent was
      successfully deployed in 95% of cases. There was an improvement in gastric outlet
      obstruction score (GOOS) in 84 (90%) of patients with the ability to tolerate an
      enteral diet. Median survival was 4.25 months (range 0-49) without any
      significant differences between types of primary malignancy. Mean hospital stay
      was 3 days (range 1-20). Reintervention rate for stent related complications was
      5%. Conclusion. The successful deployment of enteral stents achieves excellent
      palliation often resulting in the prompt reintroduction of enteral diet and early
      hospital discharge with minimal complications and reintervention. 

PMID- 24319459
TI  - Sleep duration and breast cancer phenotype.
AB  - Emerging evidence suggests that short sleep is associated with an increased risk
      of cancer; however, little has been done to study the role of sleep on tumor
      characteristics. In this study, we evaluated the relationship between sleep
      duration and tumor phenotype in 972 breast cancer patients. Sleep duration was
      inversely associated with tumor grade (univariate P = 0.032), particularly in
      postmenopausal women (univariate P = 0.018). This association did not reach
      statistical significance after adjustments for age, race, body mass index,
      hormone replacement therapy use, alcohol consumption, smoking, and physical
      activity in the entire study sample (P = 0.052), but it remained statistically
      significant (P = 0.049) among post-menopausal patients. We did not observe a
      statistically significant association between sleep duration and stage at
      diagnosis, ER, or HER2 receptor status. These results present a modest
      association between short duration of sleep and higher grade breast cancer in
      post-menopausal women. Further work needs to be done to validate these findings. 

PMID- 24319460
TI  - Long-term effectiveness of parent education using the "baby oral health" model on
      the improvement of oral health of young children.
AB  - Purpose. To determine the long-term effectiveness of comprehensive education
      given to parents and caregivers with respect to the incidence of preventable oral
      diseases, utilization of dental services, and retention of knowledge related to
      oral health. Methods. Group presentations on oral health were conducted for
      caregivers of infants (n = 161) using an interactive audio-visual aid. Followup
      occurred at 18 months. A comparison group (n = 181) was enrolled from the same
      community groups. Chi-square and Fisher's exact tests were used to analyze
      findings. Results. There was a difference in caries incidence, knowledge levels
      of caregivers, and utilization of dental services (P < 0.05) when comparing the
      SGB to the SGFU. Conclusions. One-time exposure to parent education using a
      comprehensive interactive audio-visual aid has an effect on reducing caries
      incidence and increasing dental utilization. While most knowledge is retained by
      parents, there is some attrition in the information retained over an 18-month
      time period. This emphasizes the importance of repeated reinforcement of the same
      concepts over a shorter time span. 

PMID- 24319461
TI  - Outcome of a Community-Based Oral Health Promotion Project on Primary
      Schoolchildren's Oral Hygiene Habits.
AB  - The aim of this study was to evaluate the effect of a school-based intervention
      project conducted in a mid-sized Finnish city, Laukaa on schoolchildren's oral
      health behavior. Material and Methods. In the intervention, all children received
      dental education and some of the 7-12-year-old schoolchildren received individual
      tooth brushing instructions by a dental nurse in 2009-2010. Parents were present
      at the instruction sessions. In 2009 and 2010, all the children answered a
      questionnaire or an oral hygienist on their oral health behavior without
      identification. Results. Tooth brushing frequency increased significantly among
      the schoolchildren between the years 2009 (61.2%) and 2010 (65%) (P < 0.05); more
      so among younger children (7-10-year-olds) compared to the older ones (11-12-year
      olds). The 2010 results showed a slight trend of decreasing tooth brushing
      frequency by age both among girls and boys. Younger children got significantly
      more often parental help or reminding. The girls brushed their teeth
      significantly more frequently (71.9%) than boys (57.0%). Conclusions. Our
      findings indicate that oral health intervention can be beneficial on health
      behavior especially for children at low grades. All children, 11 to 12 years of
      age, especially boys, need continuous health promotion. 

PMID- 24319462
TI  - Arthrocentesis and temporomandibular joint disorders: clinical and radiological
      results of a prospective study.
AB  - Purpose. We evaluated the efficacy of arthrocentesis in the treatment of
      temporomandibular joint (TMJ) disorders. Material and Methods. In this
      prospective clinical case series, 30 consecutive patients with TMJ disorders
      underwent arthrocentesis using saline and sodium hyaluronate injections. Outcome
      measures were TMJ pain, maximum mouth opening (MMO), joint noises, and anatomical
      changes in the TMJ architecture. Patients were evaluated using cone-beam computed
      tomography (CBCT) and magnetic resonance imaging (MRI) at the beginning of
      treatment and 60 days after the last arthrocentesis. Pretreatment and
      posttreatment clinical parameters were compared using paired and unpaired t
      tests, and McNemar's test was used to evaluate CBCT and MRI changes (P < 0.05).
      Results. At 1-year follow-up examinations, visual analogue scale scores indicated
      that pain was reduced significantly and mean postoperative MMO was increased
      significantly. CBCT findings showed no significant change, and MRI showed only
      slight reductions in inflammatory signs. Conclusions. Within the limitations of
      this study, we can conclude that arthrocentesis is a simple, minimally invasive
      procedure with a relatively low risk of complications and significant clinical
      benefits in patients with TMJ disorders. This trial is registered with
      NCT01903512. 

PMID- 24319463
TI  - Graves' disease causing pancytopenia and autoimmune hemolytic anemia at different
      time intervals: a case report and a review of the literature.
AB  - Graves' disease (GD) is associated with various hematologic abnormalities but
      pancytopenia and autoimmune hemolytic anemia (AIHA) are reported very rarely.
      Herein, we report a patient with GD who had both of these rare complications at
      different time intervals, along with a review of the related literature. The
      patient was a 70-year-old man who, during a hospitalization, was also noted to
      have pancytopenia and elevated thyroid hormone levels. Complete hematologic
      workup was unremarkable and his pancytopenia was attributed to hyperthyroidism.
      He was started on methimazole but unfortunately did not return for followup and
      stopped methimazole after a few weeks. A year later, he presented with fatigue
      and weight loss. Labs showed hyperthyroidism and isolated anemia (hemoglobin 7
      g/dL). He had positive direct Coombs test and elevated reticulocyte index. He was
      diagnosed with AIHA and started on glucocorticoids. GD was confirmed with
      elevated levels of thyroid stimulating immunoglobulins and thyroid uptake and
      scan. He was treated with methimazole and radioactive iodine ablation. His
      hemoglobin improved to 10.7 g/dL at discharge without blood transfusion. Graves'
      disease should be considered in the differential diagnosis of hematologic
      abnormalities. These abnormalities in the setting of GD generally respond well to
      antithyroid treatment. 

PMID- 24319464
TI  - Diagnosis of Cryptococcosis and Prevention of Cryptococcal Meningitis Using a
      Novel Point-of-Care Lateral Flow Assay.
AB  - Despite access to antiretroviral therapy, mortality from cryptococcal meningitis
      (CM) is high among persons with advanced HIV infection in sub-Saharan Africa.
      Cryptococcal antigen (CrAg) is present several weeks to months before the onset
      of symptoms of meningitis and can be screened to prevent life threatening
      meningitis. Recently, the World Health Organisation recommended that a new rapid
      CrAg lateral flow ''dipstick" assay (LFA) is to be used to screen HIV-infected
      persons with CD4 counts of less than 100 cells/uL. In this paper, we describe two
      cases of cryptococcosis with differing outcomes. In the first case, the new CrAg
      LFA was used as part of a screen and preemptive treatment strategy to prevent CM.
      In the second case, our patient had no access to the CrAg LFA and subsequently
      developed life threatening meningitis. To the best of our knowledge, this is the
      first case report of cryptococcosis diagnosed using this novel assay. 

PMID- 24319465
TI  - Evaluation of attention-deficit hyperactivity disorder risk factors.
AB  - Background. Attention-deficit hyperactivity disorder (ADHD) is one of the most
      common psychiatric disorders among children. The aim of this study was to
      evaluate risk factors for ADHD in children. Method. In this case-control study,
      404 children between 4 and 11 years old were selected by cluster sampling method
      from preschool children (208 patients as cases and 196 controls). All the
      participants were interviewed by a child and adolescent psychiatrist to survey
      risk factors of ADHD. Results. Among cases, 59.3% of children were boys and 38.4%
      were girls, which is different to that in control group with 40.7% boys and 61.6%
      girls. The chi-square showed statistically significance (P value < 0.0001). The
      other significant factors by chi-square were fathers' somatic or psychiatric
      disease (P value < 0.0001), history of trauma and accident during pregnancy (P
      value = 0.039), abortion proceeds (P value < 0.0001), unintended pregnancy (P
      value < 0.0001), and history of head trauma (P value < 0.0001). Conclusions.
      Findings of our study suggest that maternal and paternal adverse events were
      associated with ADHD symptoms, but breast feeding is a protective factor. 

PMID- 24319466
TI  - Persistent suppression of type 1 diabetes by a multicomponent vaccine containing
      a cholera toxin B subunit-autoantigen fusion protein and complete Freund's
      adjuvant.
AB  - Data presented here demonstrate multifunctional vaccination strategies that
      harness vaccinia virus mediated delivery of a gene encoding an immunoenhanced
      diabetes autoantigen in combination with complete Freund's adjuvant (CFA) that
      can maintain safe and durable immunologic homeostasis in NOD mice. Systemic
      coinoculation of prediabetic mice with recombinant vaccinia virus rVV-CTB::GAD
      and undiluted or 10-fold diluted CFA demonstrated a significant decrease in
      hyperglycemia and pancreatic islet inflammation in comparison with control
      animals during 17-61 and 17-105 weeks of age, respectively. Synergy in these
      beneficial effects was observed during 43-61 and 61-105 wks of age, respectively.
      Inflammatory cytokine and chemokine levels in GAD-stimulated splenocytes isolated
      from vaccinated mice were generally lower than those detected in unvaccinated
      mice. The overall health and humoral immune responses of the vaccinated animals
      remained normal throughout the duration of the experiments. 

PMID- 24319467
TI  - Enumeration and characterization of human memory T cells by enzyme-linked
      immunospot assays.
AB  - The enzyme-linked immunospot (ELISPOT) assay has advanced into a useful and
      widely applicable tool for the evaluation of T-cell responses in both humans and
      animal models of diseases and/or vaccine candidates. Using synthetic peptides
      (either individually or as overlapping peptide mixtures) or whole antigens, total
      lymphocyte or isolated T-cell subset responses can be assessed either after short
      term stimulation (standard ELISPOT) or after their expansion during a 10-day
      culture (cultured ELISPOT). Both assays detect different antigen-specific immune
      responses allowing the analysis of effector memory T cells and central memory T
      cells. This paper describes the principle of ELISPOT assays and discusses their
      application in the evaluation of immune correlates of clinical interest with a
      focus on the vaccine field. 

PMID- 24319468
TI  - Therapeutic potential of tolerogenic dendritic cells in IBD: from animal models
      to clinical application.
AB  - The gut mucosa undergoes continuous antigenic exposure from food antigens,
      commensal flora derived ligands, and pathogens. This constant stimulation results
      in controlled inflammatory responses that are effectively suppressed by multiple
      factors. This tight regulation, necessary to maintain intestinal homeostasis, is
      affected during inflammatory bowel diseases (IBD) resulting in altered immune
      responses to harmless microorganisms. Dendritic cells (DCs) are sentinels of
      immunity, located in peripheral and lymphoid tissues, which are essential for
      homeostasis of T cell-dependent immune responses. The expression of a particular
      set of pathogen recognition receptors allows DCs to initiate immune responses.
      However, in the absence of danger signals, different DC subsets can induce active
      tolerance by inducing regulatory T cells (Treg), inhibiting inflammatory T helper
      cell responses, or both. Interestingly, several protocols to generate clinical
      grade tolerogenic DC (tol-DCs) in vitro have been described, opening the
      possibility to restore the intestinal homeostasis to bacterial flora by cellular
      therapy. In this review, we discuss different DC subsets and their role in IBD.
      Additionally, we will review preclinical studies performed in animal models while
      describing recent characterization of tol-DCs from Crohn's disease patients for
      clinical application. 

PMID- 24319470
TI  - How could disclosing incidental information from whole-genome sequencing affect
      patient behavior?
AB  - In this article, we argue that disclosure of incidental findings from whole
      genome sequencing has the potential to motivate individuals to change health
      behaviors through psychological mechanisms that differ from typical risk
      assessment interventions. Their ability to do so, however, is likely to be highly
      contingent upon the nature of the incidental findings and how they are disclosed,
      the context of the disclosure and the characteristics of the patient. Moreover,
      clinicians need to be aware that behavioral responses may occur in unanticipated
      ways. This article argues for commentators and policy makers to take a cautious
      but optimistic perspective while empirical evidence is collected through ongoing
      research involving whole-genome sequencing and the disclosure of incidental
      information.

PMID- 24319469
TI  - Immunological demyelination triggers macrophage/microglial cells activation
      without inducing astrogliosis.
AB  - The glial scar formed by reactive astrocytes and axon growth inhibitors
      associated with myelin play important roles in the failure of axonal regeneration
      following central nervous system (CNS) injury. Our laboratory has previously
      demonstrated that immunological demyelination of the CNS facilitates regeneration
      of severed axons following spinal cord injury. In the present study, we evaluate
      whether immunological demyelination is accompanied with astrogliosis. We compared
      the astrogliosis and macrophage/microglial cell responses 7 days after either
      immunological demyelination or a stab injury to the dorsal funiculus. Both
      lesions induced a strong activated macrophage/microglial cells response which was
      significantly higher within regions of immunological demyelination. However,
      immunological demyelination regions were not accompanied by astrogliosis compared
      to stab injury that induced astrogliosis which extended several millimeters above
      and below the lesions, evidenced by astroglial hypertrophy, formation of a glial
      scar, and upregulation of intermediate filaments glial fibrillary acidic protein
      (GFAP). Moreover, a stab or a hemisection lesion directly within immunological
      demyelination regions did not induced astrogliosis within the immunological
      demyelination region. These results suggest that immunological demyelination
      creates a unique environment in which astrocytes do not form a glial scar and
      provides a unique model to understand the putative interaction between astrocytes
      and activated macrophage/microglial cells. 

PMID- 24319471
TI  - Faith as a resource in patients with multiple sclerosis is associated with a
      positive interpretation of illness and experience of gratitude/awe.
AB  - The aim of this cross-sectional anonymous survey with standardized questionnaires
      was to investigate which resources to cope were used by patients with multiple
      sclerosis (MS). We focussed on patients' conviction that their faith might be a
      strong hold in difficult times and on their engagement in different forms of
      spirituality. Consecutively 213 German patients (75% women; mean age 43 +/- 11
      years) were enrolled. Fifty-five percent regarded themselves as neither religious
      nor spiritual (R-S-), while 31% describe themselves as religious. For 29%, faith
      was a strong hold in difficult times. This resource was neither related to
      patients' EDSS scores, and life affections, fatigue, negative mood states, life
      satisfaction nor to Positive attitudes. Instead it was moderately associated with
      a Reappraisal strategy (i.e., and positive interpretation of illness) and
      experience of gratitude/awe. Compared to spiritual/religious patients, R-S-
      individuals had significantly (P < .0001) lower Reappraisal scores and lower
      engagement in specific forms of spiritual practices. The ability to reflect on
      what is essential in life, to appreciate and value life, and also the conviction
      that illness may have meaning and could be regarded as a chance for development
      was low in R-S- individuals which either may have no specific interest or are
      less willing to reflect these issues. 

PMID- 24319472
TI  - Religiosity and spirituality and the intake of fruit, vegetable, and fat: a
      systematic review.
AB  - Objectives. To systematically review articles investigating the relationship
      between religion and spirituality (R/S) and fruit, vegetable, and fat intake.
      Methods. PubMed, CINAHL, and PsycInfo were searched for studies published in
      English prior to March 2013. The studies were divided into two categories:
      denominational studies and degree of R/S studies. The degree of R/S studies was
      further analyzed to (1) determine the categories of R/S measures and their
      relationship with fruit, vegetable, and fat intake, (2) evaluate the quality of
      the R/S measures and the research design, and (3) determine the categories of
      reported relationship. Results. Thirty-nine studies were identified. There were
      14 denominational studies and 21 degree of R/S studies, and 4 studies were a
      combination of both. Only 20% of the studies reported validity and 52% reported
      reliability of the R/S measures used. All studies were cross-sectional, and only
      one attempted mediation analysis. Most studies showed a positive association with
      fruit and vegetable intake and a mixed association with fat intake. Conclusion.
      The positive association between R/S and fruit and vegetable intake may be one
      possible link between R/S and positive health outcome. However, the association
      with fat intake was mixed, and recommendations for future research are made. 

PMID- 24319473
TI  - Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via
      PI3K/Akt Signaling Pathway.
AB  - The neurotoxicity of amyloid- beta (A beta ) has been implicated as a critical
      cause of Alzheimer's disease. Isorhynchophylline (IRN), an oxindole alkaloid
      isolated from Uncaria rhynchophylla, exerts neuroprotective effect against Abeta
      25-35-induced neurotoxicity in vitro. However, the exact mechanism for its
      neuroprotective effect is not well understood. The present study aimed to
      investigate the molecular mechanisms underlying the protective action of IRN
      against Abeta 25-35-induced neurotoxicity in cultured rat pheochromocytoma (PC12)
      cells. Pretreatment with IRN significantly increased the cell viability,
      inhibited the release of lactate dehydrogenase and the extent of DNA
      fragmentation in Abeta 25-35-treated cells. IRN treatment was able to enhance the
      protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3 beta
      (p-GSK-3 beta ). Lithium chloride blocked Abeta 25-35-induced cellular apoptosis
      in a similar manner as IRN, suggesting that GSK-3 beta inhibition was involved in
      neuroprotective action of IRN. Pretreatment with LY294002 completely abolished
      the protective effects of IRN. Furthermore, IRN reversed Abeta 25-35-induced
      attenuation in the level of phosphorylated cyclic AMP response element binding
      protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor.
      These experimental findings unambiguously suggested that the protective effect of
      IRN against Abeta 25-35-induced apoptosis in PC12 cells was associated with the
      enhancement of p-CREB expression via PI3K/Akt/GSK-3 beta signaling pathway. 

PMID- 24319474
TI  - Tai chi exercise in medicine and health promotion.

PMID- 24319475
TI  - The Methanol Extract of Angelica sinensis Induces Cell Apoptosis and Suppresses
      Tumor Growth in Human Malignant Brain Tumors.
AB  - Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. The
      methanol extract of Angelica sinensis (AS-M) is commonly used in traditional
      Chinese medicine to treat several diseases, such as gastric mucosal damage,
      hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also
      displays potency in suppressing the growth of malignant brain tumor cells. The
      growth suppression of malignant brain tumor cells by AS-M results from cell cycle
      arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors,
      including p16, to decrease the phosphorylation of Rb proteins, resulting in
      arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M
      and correlates with activation of apoptosis-associated proteins. Therefore, the
      apoptosis of cancer cells induced by AS-M may be triggered through the p53
      pathway. In in vivo studies, AS-M not only suppresses the growth of human
      malignant brain tumors but also significantly prolongs patient survival. In
      addition, AS-M has potent anticancer effects involving cell cycle arrest,
      apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of
      AS-M indicate that this extract warrants further investigation and potential
      development as a new antibrain tumor agent, providing new hope for the
      chemotherapy of malignant brain cancer. 

PMID- 24319476
TI  - Okadaic Acid, a Bioactive Fatty Acid from Halichondria okadai, Stimulates
      Lipolysis in Rat Adipocytes: The Pivotal Role of Perilipin Translocation.
AB  - Lipid metabolism in visceral fat cells is correlated with metabolic syndrome and
      cardiovascular diseases. Okadaic-acid, a 38-carbon fatty acid isolated from the
      black sponge Halichondria okadai, can stimulate lipolysis by promoting the
      phosphorylation of several proteins in adipocytes. However, the mechanism of
      okadaic acid-induced lipolysis and the effects of okadaic acid on lipid-droplet
      associated proteins (perilipins and beta-actin) remain unclear. We isolated
      adipocytes from rat epididymal fat pads and treated them with isoproterenol
      and/or okadaic acid to estimate lipolysis by measuring glycerol release.
      Incubating adipocytes with okadaic acid stimulated time-dependent lipolysis.
      Lipid-droplet-associated perilipins and beta-actin were analyzed by
      immunoblotting and immunofluorescence, and the association of perilipin A and B
      was found to be decreased in response to isoproterenol or okadaic acid treatment.
      Moreover, okadaic-acid treatment could enhance isoproterenol-mediated lipolysis,
      whereas treatment of several inhibitors such as KT-5720 (PKA inhibitor),
      calphostin C (PKC inhibitor), or KT-5823 (PKG inhibitor) did not attenuate
      okadaic-acid-induced lipolysis. By contrast, vanadyl acetylacetonate (tyrosine
      phosphatase inhibitor) blocked okadaic-acid-dependent lipolysis. These results
      suggest that okadaic acid induces the phosphorylation and detachment of lipid
      droplet-associated perilipin A and B from the lipid droplet surface and thereby
      leads to accelerated lipolysis. 

PMID- 24319477
TI  - Jiao tai wan attenuates hepatic lipid accumulation in type 2 diabetes mellitus.
AB  - Jiao Tai Wan (JTW), a Chinese herbal formula containing Rhizoma Coptidis and
      Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of
      this study was to determine the main components in JTW and to investigate the
      effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW
      extract was prepared and the main components were assayed by HPLC. An animal
      model of diabetes mellitus was established and JTW was administered
      intragastrically. In the clinical study, diabetic patients with poor glycemic
      control were treated with JTW. Blood glucose and lipid parameters, liver
      histology, hepatic triglyceride content and lipogenic gene expression were
      examined. Our data demonstrated that JTW significantly improved hyperglycemia,
      hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was
      accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC) and
      fatty acid synthase (FAS) protein expressions, and the up-regulation of AMP
      activated protein kinase (AMPK) and phosphorylated-ACC (pACC) protein expressions
      in the liver tissues. Diabetic patients also exhibited decreases in their hepatic
      triglyceride content. The results suggest that JTW attenuates hepatic lipid
      accumulation in diabetic rats and humans. These beneficial effects are possibly
      associated with the inhibition of lipogenic gene expression in the liver. 

PMID- 24319478
TI  - Effects of wenxin keli on the action potential and L-type calcium current in rats
      with transverse aortic constriction-induced heart failure.
AB  - Objective. We investigated the effects of WXKL on the action potential (AP) and
      the L-type calcium current (I Ca-L) in normal and hypertrophied myocytes.
      Methods. Forty male rats were randomly divided into two groups: the control group
      and the transverse aortic constriction- (TAC-) induced heart failure group.
      Cardiac hypertrophy was induced by TAC surgery, whereas the control group
      underwent a sham operation. Eight weeks after surgery, single cardiac ventricular
      myocytes were isolated from the hearts of the rats. The APs and I Ca-L were
      recorded using the whole-cell patch clamp technique. Results. The action
      potential duration (APD) of the TAC group was prolonged compared with the control
      group and was markedly shortened by WXKL treatment in a dose-dependent manner.
      The current densities of the I Ca-L in the TAC group treated with 5 g/L WXKL were
      significantly decreased compared with the TAC group. We also determined the
      effect of WXKL on the gating mechanism of the I Ca-L in the TAC group. We found
      that WXKL decreased the I Ca-L by accelerating the inactivation of the channels
      and delaying the recovery time from inactivation. Conclusions. The results
      suggest that WXKL affects the AP and blocked the I Ca-L, which ultimately
      resulted in the treatment of arrhythmias. 

PMID- 24319479
TI  - The efficacy of red ginseng in type 1 and type 2 diabetes in animals.
AB  - Diabetes mellitus (DM) is one of the most modern chronic metabolic diseases in
      the world. Moreover, DM is one of the major causes of modern neurological
      diseases. In the present study, the therapeutic actions of Korean red ginseng
      were evaluated in type 1 and type 2 diabetic mouse models using auditory
      electrophysiological measurement. The comprehensive results from auditory
      brainstem response (ABR), auditory middle latency response (AMLR), and transient
      evoked otoacoustic emission (TEOAE) demonstrate auditory functional damage caused
      by type 1 or 2 DM. Korean red ginseng improved the hearing threshold shift,
      delayed latencies and signal intensity decrease in type 2 diabetic mice. Type 1
      diabetic mice showed a partial improvement in decreasing amplitude and signal
      intensity, not significantly. We suggest that the Korean red ginseng has a more
      potent efficacy in hearing loss in insulin resistance type 2 diabetes than in
      type 1 diabetes. 

PMID- 24319480
TI  - Effect of Traditional Chinese Herbal Medicine with Antiquorum Sensing Activity on
      Pseudomonas aeruginosa.
AB  - Traditional Chinese herbal medicines (TCHMs) were tested for their ability of
      antiquorum sensing. Water extracts of Rhubarb, Fructus gardeniae, and
      Andrographis paniculata show antiquorumsensing activity when using
      Chromobacterium violaceum CV12472 as reporter; the sub-MIC concentrations of
      these TCHMs were tested against AHL-dependent phenotypic expressions of PAO1.
      Results showed significant reduction in pyocyanin pigment, protease, elastase
      production, and biofilm formation in PAO1 without inhibiting the bacterial
      growth, revealing that the QSI by the extracts is not related to static or
      killing effects on the bacteria. The results indicate a potential modulation of
      bacterial cell-cell communication, P. aeruginosa biofilm, and virulence factors
      by traditional Chinese herbal medicine. This study introduces not only a new mode
      of action for traditional Chinese herbal medicines, but also a potential new
      therapeutic direction for the treatment of bacterial infections, which have QSI
      activity and might be important in reducing virulence and pathogenicity of
      pathogenic bacteria. 

PMID- 24319481
TI  - Antidiabetic Effect of Oral Borapetol B Compound, Isolated from the Plant
      Tinospora crispa, by Stimulating Insulin Release.
AB  - Aims. To evaluate the antidiabetic properties of borapetol B known as compound 1
      (C1) isolated from Tinospora crispa in normoglycemic control Wistar (W) and
      spontaneously type 2 diabetic Goto-Kakizaki (GK) rats. Methods. The effect of C1
      on blood glucose and plasma insulin was assessed by an oral glucose tolerance
      test. The effect of C1 on insulin secretion was assessed by batch incubation and
      perifusion experiments using isolated pancreatic islets. Results. An acute oral
      administration of C1 improved blood glucose levels in treated versus placebo
      groups with areas under glucose curves 0-120 min being 72 +/- 17 versus 344 +/-
      10 mmol/L (P < 0.001) and 492 +/- 63 versus 862 +/- 55 mmol/L (P < 0.01) in W and
      GK rats, respectively. Plasma insulin levels were increased by 2-fold in treated
      W and GK rats versus placebo group at 30 min (P < 0.05). C1 dose-dependently
      increased insulin secretion from W and GK isolated islets at 3.3 mM and 16.7 mM
      glucose. The perifusions of isolated islets indicated that C1 did not cause
      leakage of insulin by damaging islet beta cells (P < 0.001). Conclusion. This
      study provides evidence that borapetol B (C1) has antidiabetic properties mainly
      due to its stimulation of insulin release. 

PMID- 24319482
TI  - Attachment theory and spirituality: two threads converging in palliative care?
AB  - The aim of this paper is to discuss and explore the interrelation between two
      concepts, attachment theory and the concept of spirituality, which are important
      to palliative care and to founding a multivariate understanding of the patient's
      needs and challenges. Both concepts have been treated by research in diverse and
      multiform ways, but little effort has yet been made to integrate them into one
      theoretical framework in reference to the palliative context. In this paper, we
      begin an attempt to close this scientific gap theoretically. Following the lines
      of thought in this paper, we assume that spirituality can be conceptualized as an
      adequate response of a person's attachment pattern to the peculiarity of the
      palliative situation. Spirituality can be seen both as a recourse to securely
      based relationships and as an attempt to explore the ultimate unknown, the
      mystery of one's own death. Thus, spirituality in the palliative context
      corresponds to the task of attachment behavior: to transcend symbiosis while
      continuing bonds and thus to explore the unknown environment independently and
      without fear. Spiritual activity is interpreted as a human attachment behavior
      option that receives special quality and importance in the terminal stage of
      life. Implications for clinical practice and research are discussed in the final
      section of the paper. 

PMID- 24319484
TI  - Effects of low level laser therapy on ovalbumin-induced mouse model of allergic
      rhinitis.
AB  - Introduction. This study was designed to investigate the effects of low level
      laser therapy (LLLT) on experimental allergic rhinitis (AR) models induced by
      ovalbumin. Materials and Methods. AR was induced by 1% ovalbumin in mice. Twenty
      four mice were divided into 4 groups: normal, control, low, and high dose
      irradiation. Low and high dose LLLT were irradiated once a day for 7 days. Total
      IgE, cytokines concentrations (IL-4 and IFN- gamma ), and thymus and activation
      regulated chemokine (TARC) were measured. Histological changes in the nasal
      mucosal tissue by laser irradiation were examined. Results. LLLT significantly
      inhibited total IgE, IL-4, and TARC expression in ovalbumin-induced mice at low
      dose irradiation. The protein expression level of IL-4 in spleen was inhibited in
      low dose irradiation significantly. IL-4 expression in EL-4 cells was inhibited
      in a dose dependent manner. Histological damages of the epithelium in the nasal
      septum were improved by laser irradiation with marked improvement at low dose
      irradiation. Conclusion. These results suggest that LLLT might serve as a new
      therapeutic tool in the treatment of AR with more effectiveness at low dose
      irradiation. To determine the optimal dose of laser irradiation and action
      mechanisms of laser therapy, further studies will be needed. 

PMID- 24319483
TI  - Prunus mume and Lithospermum erythrorhizon Extracts Synergistically Prevent
      Visceral Adiposity by Improving Energy Metabolism through Potentiating
      Hypothalamic Leptin and Insulin Signalling in Ovariectomized Rats.
AB  - We investigated the antiobesity and hypoglycemic properties of Prunus mume Sieb.
      et Zucc (PMA; Japanese apricot) and Lithospermum erythrorhizon Sieb. et Zucc
      (LES; gromwell) extracts in ovariectomized (OVX) rats that impaired energy and
      glucose homeostasis. OVX rats consumed either 5% dextrose, 5% PMA extract, 5% LES
      extract, or 2.5% PMA+2.5% LES extract in the high fat diet. After 8 weeks of
      treatment, PMA+LES prevented weight gain and visceral fat accumulation in OVX
      rats by lowering daily food intake and increasing energy expenditure and fat
      oxidation. PMA+LES prevented the attenuation of leptin and insulin signaling by
      increasing the expression of leptin receptor in the hypothalamus in OVX rats.
      PMA+LES significantly reversed the decrease of energy expenditure in OVX rats by
      increasing expression of UCP-1 in the brown adipose tissues and UCP-2 and UCP-3
      in the quadriceps muscles. PMA+LES also increased CPT-1 expression and decreased
      FAS, ACC, and SREBP-1c in the liver and quadriceps muscles to result in reducing
      triglyceride accumulation. PMA+LES improved insulin sensitivity in OVX rats. In
      conclusion, PMA+LES synergistically prevented the impairment of energy, lipid,
      and glucose metabolism by OVX through potentiating hypothalamic leptin and
      insulin signaling. PMA+LES may be a useful intervention for alleviating the
      symptoms of menopause in women. 

PMID- 24319485
TI  - Postischemic Long-Term Treatment with Qiangli Tianma Duzhong Capsule Improves
      Brain Functional Recovery via the Improvement of Hemorrheology and the Inhibition
      of Platelet Aggregation in a Rat Model of Focal Cerebral Ischemia.
AB  - Qiangli Tianma Duzhong capsule (TMDZ), a Chinese herbal drug, is clinically used
      to improve functional outcome in patients with ischemic stroke in China. This
      study was conducted to establish whether postischemic long-term treatment with
      TMDZ could reduce the loss of injured hemisphere and confer the improvements of
      neurological outcome in chronic survival of rats with 2 h middle cerebral artery
      occlusion (MCAO)/reperfusion brain injury and its primary mechanisms. We found
      that TMDZ (44.5, 89, or 178 mg/kg), administered per os 6 h after the onset of
      ischemia and for 28 consecutive days, significantly improved the behavior
      deficits, beginning on day 7, and further improved later. TMDZ treatment also
      markedly reduced the tissue loss of the injured hemisphere and improved
      histopathology. In the meantime, TMDZ treatment could improve hemorrheology and
      inhibit platelet aggregation. These results provide the first evidence that post
      ischemic long-term treatment with TMDZ confers the improvements of neurological
      outcome and the loss of injured hemisphere in an animal ischemic stroke model,
      and its mechanisms might be associated with the improvements of hemorrheology and
      the inhibition of platelet aggregation. 

PMID- 24319486
TI  - Combination Therapy of Sophoraflavanone B against MRSA: In Vitro Synergy Testing.
AB  - Sophoraflavanone B (SPF-B), a known prenylated flavonoid, was isolated from the
      roots of Desmodium caudatum. The aim of this study was to determine the
      antimicrobial synergism of SPF-B combined with antibiotics against methicillin
      resistant Staphylococcus aureus (MRSA). MRSA, a multidrug-resistant pathogen,
      causes both hospital- and community-acquired infections worldwide. The
      antimicrobial activity of SPF-B was assessed by the broth microdilution method,
      checkerboard dilution test, and time-kill curve assay. The MIC of SPF-B for 7
      strains of S. aureus ranges from 15.6 to 31.25  MU g/mL determined. In the
      checkerboard method, the combinations of SPF-B with antibiotics had a synergistic
      effect; SPF-B markedly reduced the MICs of the beta -lactam antibiotics:
      ampicillin (AMP) and oxacillin (OXI); aminoglycosides gentamicin (GET);
      quinolones ciprofloxacin (CIP) and norfloxacin (NOR) against MRSA. The time-kill
      curves assay showed that a combined SPF-B and selected antibiotics treatment
      reduced the bacterial counts below the lowest detectable limit after 24 h. These
      data suggest that the antibacterial activity of SPF-B against MRSA can be
      effectively increased through its combination with three groups of antibiotics (
      beta -lactams, aminoglycosides, and quinolones). Our research can be a valuable
      and significant source for the development of a new antibacterial drug with low
      MRSA resistance. 

PMID- 24319487
TI  - Effects of Korean Red Ginseng and HAART on vif Gene in 10 Long-Term Slow
      Progressors over 20 Years: High Frequency of Deletions and G-to-A Hypermutation.
AB  - To investigate if Korean red ginseng (KRG) affects vif gene, we determined vif
      gene over 20 years in 10 long-term slowly progressing patients (LTSP) who were
      treated with KRG alone and then KRG plus HAART. We also compared these data with
      those of 21 control patients who did not receive KRG. Control patient group
      harbored only one premature stop codon (PSC) (0.9%), whereas the 10 LTSP revealed
      78 defective genes (18.1%) (P < 0.001). The frequency of small in-frame deletions
      was found to be significantly higher in patients who received KRG alone (10.5%)
      than 0% in the pre-KRG or control patients (P < 0.01). Regarding HAART, vif genes
      containing PSCs were more frequently detected in patients receiving KRG plus
      HAART than patients receiving KRG alone or control patients (P < 0.01). In
      conclusion, our current data suggest that the high frequency of deletions and PSC
      in the vif gene is associated with KRG intake and HAART, respectively. 

PMID- 24319488
TI  - A review on bioactivities of perilla: progress in research on the functions of
      perilla as medicine and food.
AB  - Perilla is a useful pharmaceutical and food product and is empirically consumed
      by humans. However, its properties have not been evaluated extensively. In this
      review, we summarize the progress made in research, focusing on the bioactivities
      of perilla. There are many in vitro and animal studies on the cytostatic activity
      and antiallergic effects, respectively, of perilla and its constituents. However,
      its influence on humans remains unclear. Hence, investigating and clarifying the
      physiological effects of perilla and its constituents on humans are imperative in
      the future to adhere to the ideals of evidence-based medicine. 

PMID- 24319489
TI  - Antiobesity effect of caraway extract on overweight and obese women: a
      randomized, triple-blind, placebo-controlled clinical trial.
AB  - Caraway (Carum carvi L.), a potent medicinal plant, is traditionally used for
      treating obesity. This study investigates the weight-lowering effects of caraway
      extract (CE) on physically active, overweight and obese women through a
      randomized, triple-blind, placebo-controlled clinical trial. Seventy overweight
      and obese, healthy, aerobic-trained, adult females were randomly assigned to two
      groups (n = 35 per group). Participants received either 30 mL/day of CE or
      placebo without changing their diet or physical activity. Subjects were examined
      at baseline and after 90 days for changes in body composition, anthropometric
      indices, and clinical and paraclinical variables. The treatment group, compared
      with placebo, showed a significant reduction of weight, body mass index, body fat
      percentage, and waist-to-hip ratio. No changes were observed in lipid profile,
      urine-specific gravity, and blood pressure of subjects. The results suggest that
      a dietary CE with no restriction in food intake, when combined with exercise, is
      of value in the management of obesity in women wishing to lower their weight,
      BMI, body fat percentage, and body size, with no clinical side effects. In
      conclusion, results of this study suggest a possible phytotherapeutic approach
      for caraway extract in the management of obesity. This trial is registered with
      NCT01833377. 

PMID- 24319490
TI  - Identification of immunomodulatory signatures induced by american ginseng in
      murine immune cells.
AB  - Background. American ginseng (Panax quinquefolius, AG) has been used for more
      than 300 years. Some of its claimed benefits can be attributed to the
      immunomodulatory activities, whose molecular mechanisms are largely unknown.
      Methods. Murine splenic cells from adult male C57BL/6 (B6) mice were isolated and
      divided into 4 groups to mimic 4 basic pathophysiological states: (1) normal
      naive; (2) normal activated; (3) deficient naive; (4) deficient activated. Then,
      different AG extracts were added to all groups for 24 h incubation. MTT
      proliferation assays were performed to evaluate the phenotypic features of cells.
      Finally, microarray assays were carried out to identify differentially expressed
      genes associated with AG exposure. Real-time PCR was performed to validate the
      expression of selected genes. Results. Microarray data showed that most of gene
      expression changes were identified in the deficient naive group, suggesting that
      the pathophysiological state has major impacts on transcriptomic changes
      associated with AG exposure. Specifically, this study revealed downregulation of
      interferon- gamma signaling pathway in the deficient group of cells. Conclusion.
      Our study demonstrated that only specific groups of immune cells responded to AG
      intervention and immunocompromised cells were more likely regulated by AG
      treatment. 

PMID- 24319491
TI  - PAMAM Dendrimers as Quantized Building Blocks for Novel Nanostructures.
AB  - The desire to synthesize soft supramolecular structures with size scales similar
      to biological systems has led to work in assembly of polymeric nanomaterials.
      Recent advances in the isolation of generationally homogenous poly(amidoamine)
      (PAMAM) dendrimer enables their use as quantized building blocks. Here, we report
      their assembly into precise nanoclusters. In this work, click-functional ligands
      are stochastically conjugated to monomeric generation 5 PAMAM dendrimer and
      separated via reverse-phase HPLC to isolate dendrimers with precise numbers of
      click ligands per dendrimer particle. The click-ligand/dendrimer conjugates are
      then employed as modular building blocks for the synthesis of defined
      nanostructures. Complimentary click chemistry employing dendrimers with 1, 2, 3,
      or 4 ring-strained cyclooctyne ligands and dendrimers with 1 azide ligand were
      utilized to prepare megamer structures containing 2 to 5 ~30,000 kDa monomer
      units as characterized by mass spectrometry, size exclusion chromatography, and
      reverse-phase liquid chromatography. The resulting structures are flexible with
      masses ranging from 60,000 to 150,000 kDa, and are soluble in water, methanol,
      and dimethylsulfoxide.

PMID- 24319492
TI  - Universality in network dynamics.
AB  - Despite significant advances in characterizing the structural properties of
      complex networks, a mathematical framework that uncovers the universal properties
      of the interplay between the topology and the dynamics of complex systems
      continues to elude us. Here we develop a self-consistent theory of dynamical
      perturbations in complex systems, allowing us to systematically separate the
      contribution of the network topology and dynamics. The formalism covers a broad
      range of steady-state dynamical processes and offers testable predictions
      regarding the system's response to perturbations and the development of
      correlations. It predicts several distinct universality classes whose
      characteristics can be derived directly from the continuum equation governing the
      system's dynamics and which are validated on several canonical network-based
      dynamical systems, from biochemical dynamics to epidemic spreading. Finally, we
      collect experimental data pertaining to social and biological systems,
      demonstrating that we can accurately uncover their universality class even in the
      absence of an appropriate continuum theory that governs the system's dynamics.

PMID- 24319493
TI  - Material discrimination based on K-edge characteristics.
AB  - Spectral/multienergy CT employing the state-of-the-art energy-discriminative
      photon-counting detector can identify absorption features in the multiple ranges
      of photon energies and has the potential to distinguish different materials based
      on K-edge characteristics. K-edge characteristics involve the sudden attenuation
      increase in the attenuation profile of a relatively high atomic number material.
      Hence, spectral CT can utilize material K-edge characteristics (sudden
      attenuation increase) to capture images in available energy bins (levels/windows)
      to distinguish different material components. In this paper, we propose an
      imaging model based on K-edge characteristics for maximum material discrimination
      with spectral CT. The wider the energy bin width is, the lower the noise level
      is, but the poorer the reconstructed image contrast is. Here, we introduce the
      contrast-to-noise ratio (CNR) criterion to optimize the energy bin width after
      the K-edge jump for the maximum CNR. In the simulation, we analyze the
      reconstructed image quality in different energy bins and demonstrate that our
      proposed optimization approach can maximize CNR between target region and
      background region in reconstructed image. 

PMID- 24319494
TI  - Electromagnetic tissue properties imaging for biomedical applications.

PMID- 24319495
TI  - Theoretical Hill-type muscle and stability: numerical model and application.
AB  - The construction of artificial muscles is one of the most challenging
      developments in today's biomedical science. The application of artificial muscles
      is focused both on the construction of orthotics and prosthetics for
      rehabilitation and prevention purposes and on building humanoid walking machines
      for robotics research. Research in biomechanics tries to explain the functioning
      and design of real biological muscles and therefore lays the fundament for the
      development of functional artificial muscles. Recently, the hyperbolic Hill-type
      force-velocity relation was derived from simple mechanical components. In this
      contribution, this theoretical yet biomechanical model is transferred to a
      numerical model and applied for presenting a proof-of-concept of a functional
      artificial muscle. Additionally, this validated theoretical model is used to
      determine force-velocity relations of different animal species that are based on
      the literature data from biological experiments. Moreover, it is shown that an
      antagonistic muscle actuator can help in stabilising a single inverted pendulum
      model in favour of a control approach using a linear torque generator. 

PMID- 24319496
TI  - Haptic-based neurorehabilitation in poststroke patients: a feasibility
      prospective multicentre trial for robotics hand rehabilitation.
AB  - Background. Haptic robots allow the exploitation of known motor learning
      mechanisms, representing a valuable option for motor treatment after stroke. The
      aim of this feasibility multicentre study was to test the clinical efficacy of a
      haptic prototype, for the recovery of hand function after stroke. Methods. A
      prospective pilot clinical trial was planned on 15 consecutive patients enrolled
      in 3 rehabilitation centre in Italy. All the framework features of the haptic
      robot (e.g., control loop, external communication, and graphic rendering for
      virtual reality) were implemented into a real-time MATLAB/Simulink environment,
      controlling a five-bar linkage able to provide forces up to 20 [N] at the end
      effector, used for finger and hand rehabilitation therapies. Clinical (i.e., Fugl
      Meyer upper extremity scale; nine hold pegboard test) and kinematics (i.e., time;
      velocity; jerk metric; normalized jerk of standard movements) outcomes were
      assessed before and after treatment to detect changes in patients' motor
      performance. Reorganization of cortical activation was detected in one patient by
      fMRI. Results and Conclusions. All patients showed significant improvements in
      both clinical and kinematic outcomes. Additionally, fMRI results suggest that the
      proposed approach may promote a better cortical activation in the brain. 

PMID- 24319497
TI  - Synchronous bilateral breast cancer in a male.
AB  - Male breast cancer, which represents only 1% of all breast cancers, is
      occasionally associated with a family history of breast cancer. Sporadic male
      breast cancers presenting with another primary breast cancer are extremely rare.
      In this article, we report on a 70-year-old male patient with bilateral
      multifocal and synchronous breast cancer and without a family history of breast
      cancer. 

PMID- 24319499
TI  - A Sensitized Emission Based Calibration of FRET Efficiency for Probing the
      Architecture of Macromolecular Machines.
AB  - Macromolecular machines participate in almost every cell biological function.
      These machines can take the form of well-defined protein structures such as the
      kinetochore, or more loosely organized protein assemblies like the endocytic
      coat. The protein architecture of these machines-the arrangement of multiple
      copies of protein subunits at the nanoscale, is necessary for understanding their
      cell biological function and biophysical mechanism. Defining this architecture in
      vivo presents a major challenge. High density of protein molecules within
      macromolecular machines severely limits the effectiveness of super-resolution
      microscopy. However, this density is ideal for Forster Resonance Energy Transfer
      (FRET), which can determine the proximity between neighboring molecules. Here, we
      present a simple FRET quantitation scheme that calibrates a standard
      epifluorescence microscope for measuring donor-acceptor separations. This
      calibration can be used to deduce FRET efficiency fluorescence intensity
      measurements. This method will allow accurate determination of FRET efficiency
      over a wide range of values and FRET pair number. It will also allow dynamic FRET
      measurements with high spatiotemporal resolution under cell biological
      conditions. Although the poor maturation efficiency of genetically encoded
      fluorescent proteins presents a challenge, we show that its effects can be
      alleviated. To demonstrate this methodology, we probe the in vivo architecture of
      the gamma-Tubulin Ring. Our technique can be applied to study the architecture
      and dynamics of a wide range of macromolecular machines.

PMID- 24319500
TI  - A case report of segmental arterial mediolysis in which computed tomography
      angiography was useful for diagnosis.
AB  - A 48-year-old male presented to our hospital with abdominal pain. Laboratory
      studies showed no abnormality, the severity of his abdominal pain decreased, and
      the patient was discharged. Five days later, the patient visited a neighborhood
      clinic because of fever with a 3-day history of temperatures of approximately 38 
      degrees C. The patient was admitted to our hospital 6 days after his initial
      visit. Laboratory investigation revealed a C-reactive protein level of 18.2
      mg/dL. Abdominal computed tomography (CT) showed an 80 * 60 mm hematoma behind
      the descending colon, but no extravasation was detected. Thin-slice maximum
      intensity-projection images from CT angiography (CTA) showed irregular narrowing
      and intermittent fusiform dilatations of the left colonic artery, suggesting a
      vascular disease, such as segmental arterial mediolysis (SAM). Digital
      subtraction angiography showed local irregularity, and 'beading and narrowing' of
      the left colonic artery, similar to the findings on CTA. Left hemicolectomy was
      electively performed on the twenty-fifth hospital day. Histological findings were
      consistent with SAM. Thus, CTA was a useful modality for the early diagnosis of
      SAM. 

PMID- 24319498
TI  - Quantitative analysis of structural neuroimaging of mesial temporal lobe
      epilepsy.
AB  - Mesial temporal lobe epilepsy (MTLE) is the most common of the surgically
      remediable drug-resistant epilepsies. MRI is the primary diagnostic tool to
      detect anatomical abnormalities and, when combined with EEG, can more accurately
      identify an epileptogenic lesion, which is often hippocampal sclerosis in cases
      of MTLE. As structural imaging technology has advanced the surgical treatment of
      MTLE and other lesional epilepsies, so too have the analysis techniques that are
      used to measure different structural attributes of the brain. These techniques,
      which are reviewed here and have been used chiefly in basic research of epilepsy
      and in studies of MTLE, have identified different types and the extent of
      anatomical abnormalities that can extend beyond the affected hippocampus. These
      results suggest that structural imaging and sophisticated imaging analysis could
      provide important information to identify networks capable of generating
      spontaneous seizures and ultimately help guide surgical therapy that improves
      postsurgical seizure-freedom outcomes.

PMID- 24319501
TI  - Solitary rib recurrence of hilar cholangiocarcinoma 10 years after resection:
      report of a case.
AB  - A 61-year-old female underwent right hemihepatectomy and caudate lobectomy for
      hilar cholangiocarcinoma in 1999. Ten years later, increasing serum carbohydrate
      19-9 was detected by routine follow-up. Subsequent positron emission tomography
      revealed an asymptomatic lesion in the right 11th rib. As the mass steadily grew
      in size, the lesion was resected en bloc with the affected rib and muscle. The
      histopathological findings closely resembled those of the primary
      cholangiocarcinoma. Thus, the tumor was diagnosed as a metastatic recurrence 10
      years after resection of the primary tumor. There have been a few reports of
      cholangiocarcinoma recurrence in long-term survivors at the surgical margins,
      peritoneum, or transhepatic drainage route. However, there are no reports of
      solitary extra-abdominal recurrence. This case highlights the need for careful
      follow-up of patients with cholangiocarcinoma and nodal metastasis, even in the
      absence of recurrence for >5 years after curative resection. 

PMID- 24319502
TI  - Docking Studies of Methylthiomorpholin Phenols (LQM300 Series) with Angiotensin
      Converting Enzyme (ACE).
AB  - A main target in the treatment of hypertension is the angiotensin-converting
      enzyme (ACE). This enzyme is responsible for producing angiotensin II, a potent
      vasoconstrictor. Therefore, one of the targets in the treatment of hypertension
      is to inhibit ACE activity. Hence, this study's aim is to use computational
      studies to demonstrate that the proposed heterocyclic compounds have a molecular
      affinity for ACE and that, furthermore, these heterocyclic compounds are capable
      of inhibiting ACE activity, thus avoiding the production of the vasopressor
      Angiotensin II. All this using computer-aided drug design, and studying the
      systems, with the proposed compounds, through molecular recognition process and
      compared with the compounds already on the market for hypertension. 

PMID- 24319503
TI  - Modeling the evolution of gene regulatory networks for spatial patterning in
      embryo development.
AB  - A central question in evolutionary biology concerns the transition between
      discrete numbers of units (e.g. vertebrate digits, arthropod segments). How do
      particular numbers of units, robust and characteristic for one species, evolve
      into another number for another species? Intermediate phases with a diversity of
      forms have long been theorized, but these leave little fossil or genomic data. We
      use evolutionary computations (EC) of a gene regulatory network (GRN) model to
      investigate how embryonic development is altered to create new forms. The
      trajectories are epochal and non-smooth, in accord with both the observed
      stability of species and the evolvability between forms.

PMID- 24319504
TI  - The editorial process: Conflicts of interest.

PMID- 24319506
TI  - What has the CUA done for you lately?

PMID- 24319507
TI  - Canadian guidelines for postoperative surveillance of upper urinary tract
      urothelial carcinoma.

PMID- 24319508
TI  - Neoadjuvant chemotherapy should be administered to fit patients with newly
      diagnosed, potentially resectable muscle-invasive urothelial cancer of the
      bladder (MIBC): A 2013 CAGMO Consensus Statement and Call for a Streamlined
      Referral Process.
AB  - Neoadjuvant chemotherapy (NC) improves overall survival in patients with
      resectable muscle-invasive urothelial cancer of the bladder (MIBC). However
      uptake of NC in Canada is dis-appointingly low. Following a detailed literature
      review and in consultation with urologic oncology, the Canadian Association of
      Genitourinary Medical Oncologists (CAGMO) has developed a consensus statement for
      the use of NC in MIBC. Our primary goal is to increase the uptake of NC for MIBC
      in Canada and improve patient outcomes. 

PMID- 24319510
TI  - Evaluation and screening for hereditary renal cell cancers.

PMID- 24319509
TI  - Canadian guideline on genetic screening for hereditary renal cell cancers.
AB  - BACKGROUND: Hereditary renal cell cancer (RCC) is an ideal model for germline
      genetic testing. We propose a guideline of hereditary RCC specific criteria to
      suggest referral for genetic assessment. METHODS: A review of the literature and
      stakeholder resources for existing guidelines or consensus statements was
      performed. Referral criteria were developed by expert consensus. RESULTS: The
      criteria included characteristics for patients with RCC (age <=45 years,
      bilateral or multifocal tumours, associated medical conditions and non-clear cell
      histologies with unusual features) and for patients with or without RCC, but a
      family history of specific clinical or genetic diagnoses. CONCLUSIONS: This
      guideline represents a practical RCC-specific reference to allow healthcare
      providers to identify patients who may have a hereditary RCC syndrome, without
      extensive knowledge of each syndrome. RCC survivors and their families can also
      use the document to guide their discussions with healthcare providers about their
      need for referral. The criteria refer to the most common hereditary renal tumour
      syndromes and do not represent a comprehensive or exclusive list. Prospective
      validation of the criteria is warranted.

PMID- 24319512
TI  - Reporting the Canadian robotic experience: The outcomes and how we report them.

PMID- 24319511
TI  - Perioperative, oncological and functional outcomes of the first robotic
      prostatectomy program in Quebec: Single fellowship-trained surgeon's experience
      of 250 cases.
AB  - BACKGROUND: Robotic-assisted radical prostatectomy (RARP) is being increasingly
      done in Canada. Despite this, the Canadian literature lacks publications on the
      oncologic and functional outcomes of RARP. The objective of this study is to
      report the longest single surgeon experience in the province of Quebec. METHODS:
      We collected prospective data from 250 consecutive patients who underwent RARP by
      a single fellowship trained surgeon (AEH) from October 2006 to October 2012. Mean
      follow-up was 28 months (range: 1-72). The D'Amico risk stratification
      distribution was 34% in low-risk, 48% in intermediate-risk and 18% in high-risk
      groups. RESULTS: The mean operation time (+/-SD) was 194 +/- 60.6 minutes, and
      estimated blood loss 318 +/- 179 mL. The transfusion rate was only 0.4%. All
      procedures were completed robotically. The mean hospital stay was 1.2 days, and
      88% of patients were discharged on postoperative day 1. The mean catheterization
      time was 7 days (range: 6-13). There were 2% major (Clavien III-IV) and 7.2%
      minor (Clavien I-II) postoperative complications, and no mortalities. On final
      pathology, 76% of patients were organ-confined and 70% specimen-confined.
      Pathological Gleason sum >=7 accounted for 86%. Return of urinary continence (0
      pads) at 3, 6, 12, and 24 months was 73.3%, 83.5%, 92.3%, 96.5%, respectively.
      Potency rate (successful penetration with or without medication) at 6, 12, and 24
      months was 49.3%, 85%, and 95.3%, respectively. Operative time and positive
      surgical margin (PSM) in organ-con-fined disease (pT2) decreased significantly
      after 50 cases. Seventeen patients (6.8%) had no undetectable prostate-specific
      antigen (PSA) at first visit (PSA <0.1 ng/mL). Of remaining 233 patients,
      biochemical recurrence (PSA >0.2 ng/mL) was 4.7% (11 patients), and another 3.4%
      (8 patients) received early salvage radiotherapy (rising PSA, but <0.2 ng/mL). No
      patients with undetectable PSA required salvage treatments within 6 months
      postoperatively. CONCLUSIONS: Our results compare favourably with high-volume
      RARP programs, despite mainly intermediate- to high-risk disease. Initial
      learning curve was estimated to be 50 cases. Fellowship training was instrumental
      in achieving adequate functional and oncological outcomes, while maintaining low
      complications rate.

PMID- 24319513
TI  - A prospective trial of GreenLight PVP (HPS120) versus transurethral resection of
      the prostate in the treatment of lower urinary tract symptoms in Ontario, Canada.
AB  - BACKGROUND: Photoselective vaporization of the prostate (PVP) is a bloodless,
      relatively painless alternative to transurethral resection of the prostate (TURP)
      for relief of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia
      (BPH). OBJECTIVE: We compare the effectiveness, safety and cost-effectiveness of
      Greenlight Laser PVP (HPS-120) and TURP. METHODS: We conducted a prospective, non
      randomized trial in 3 Ontario centres from March 2008 to February 2011.
      Assessments were completed at baseline, 1 and 6 months following surgery at the
      physicians' offices and at 12 and 24 months by phone. The primary outcome was the
      change in International Prostate Symptoms Score (IPSS) score at 6 months versus
      baseline. Secondary outcomes were changes in flow rate, postvoid residual (PVR),
      prostate-specific antigen (PSA) and sexual health inventory for men (SHIM)
      scores. Adverse events, health-related quality of life (HRQoL), resource
      utilization and productivity losses were collected. RESULTS: Although the IPSS
      decreased in both arms (n = 140 for PVP and n = 24 for TURP) between baseline and
      6 months, the difference in change over time between the groups was not
      statistically significant (p = 0.718). Other outcomes improved equally from
      baseline and 6 months (Qmax, SHIM, PSA and HRQoL), with only changes in PVR
      favouring PVP (p = 0.018). There were no statistical differences in serious
      adverse events. In total, 130 of 140 PVP patients were outpatients, all TURP
      subjects were inpatients. PVP was less costly than TURP ($3891 vs. $4863; p <
      0.001) with similar quality-adjusted life years (0.448 vs. 0.441; p = 0.658).
      CONCLUSION: Greenlight Laser PVP (HPS-120) is a safe and cost-effective
      alternative to TURP for outpatient treatment of LUTS and can be completed as an
      outpatient with minimal blood loss.

PMID- 24319514
TI  - A prospective analysis of consultation for difficult urinary catheter insertion
      at tertiary care centres in Northern Alberta.
AB  - BACKGROUND: Difficult urinary catheterization (DUC) is a frequent reason for
      urologic consultation. Literature regarding DUC is limited. The objective of the
      study is to examine the current practice pattern of DUC and identify strategies
      to reduce its incidence and related adverse events. METHODS: This is a
      prospective observational study of consultation for DUC at tertiary care centres
      in Edmonton, Alberta between October 2010 and February 2011. All urologic
      consultations for DUC in adults at the 2 tertiary hospitals were enrolled.
      Patients were managed according to the current regional standard of care
      established prior to the study. A clinical encounter questionnaire (CEQ) was
      completed by the urology service regarding details of the consultation and
      patient factors. CEQ results were tabulated and analyzed for trends, areas of
      strengths and weakness in the consultation process. RESULTS: In total, 89
      patients were accrued to the study. Mean age was 67 years and 91% were male.
      Seventeen percent of patients had history of previous DUC and 65% had urologic
      history. Forty-two percent of patients had catheter placement without any
      auxiliary tools. Adverse events, including urosepsis, bladder perforation,
      hydrouterus, paraphimosis and urethral trauma, were experienced by 37% of
      patients. Significant urethral injury as a result of catheterization attempts
      occurred in 32%. Forty-one percent of consultations were classified as
      inappropriate and 53% occurred between 5 pm and 6:30 am. CONCLUSION: DUC is
      associated with significant patient morbidity and may often be preventable. This
      study highlights the need for implementation of preventive strategies, widespread
      education and increased awareness regarding catheter care.

PMID- 24319516
TI  - Northeastern Section of the American Urological Association 65(th) Annual
      Meeting, Saratoga Springs, NY Scientific Program.

PMID- 24319515
TI  - Robot-assisted laparoscopic partial nephrectomy: Early single Canadian
      institution experience.
AB  - BACKGROUND: Although robot-assisted partial nephrectomy (RALPN) has been
      increasingly adopted, open procedures continue to be the reference nephron
      sparing technique. We describe our initial surgical outcomes of RALPN in our
      single institution robotic program. METHODS: Between January 2011 and February
      2013, 65 consecutive patients underwent a RALPN by 2 surgeons. Preoperative
      characteristics, including the R.E.N.A.L. nephrometry score, perioperative
      parameters, and postoperative course, including renal function, were assessed
      from a retrospective database. The mean follow-up was 12 months. RESULTS: The
      mean age was 60.2 years and the mean tumour size was 3.9 cm. According to the
      R.E.N.A.L. nephrometry score, the tumours were classified moderately and highly
      complex tumours in 51% and 18.5% of cases, respectively. Median warm ischemia
      time (WIT) was 21 minutes. Factors associated with WIT were R.E.N.A.L.
      nephrometry score, tumour size, complication rates and surgeon experience. No
      conversion or grade 4 to 5 complications were reported. The mean hospital stay
      was 3 days. The overall complication rate was 24.6% (re-admission rate 7.7%), and
      decreased to 12% after 20 cases. After these initial 20 cases, a trifecta rate
      (no margins, preserved renal function, no complications) of 64.3% was achieved in
      moderately and highly complex tumours. The mean change in estimated glomerular
      filtration rate was 6.7 mL/min without severe postoperative renal failure.
      INTERPRETATION: RALPN is a safe and feasible procedure with low specific
      morbidity, even in moderately or highly complex renal masses. The WIT depends on
      tumour characteristics, mainly determined by the R.E.N.A.L. nephrometry score and
      is improved by surgeon experience. Longer follow-up is needed to assess the
      oncologic mid-term safety of the procedure.

PMID- 24319517
TI  - Rapid mutation of Spirulina platensis by a new mutagenesis system of atmospheric
      and room temperature plasmas (ARTP) and generation of a mutant library with
      diverse phenotypes.
AB  - In this paper, we aimed to improve the carbohydrate productivity of Spirulina
      platensis by generating mutants with increased carbohydrate content and growth
      rate. ARTP was used as a new mutagenesis tool to generate a mutant library of S.
      platensis with diverse phenotypes. Protocol for rapid mutation of S. platensis by
      60 s treatment with helium driven ARTP and high throughput screening method of
      the mutants using the 96-well microplate and microplate reader was established. A
      mutant library of 62 mutants was then constructed and ideal mutants were selected
      out. The characteristics of the mutants after the mutagenesis inclined to be
      stable after around 9(th) subculture, where the total mutation frequency and
      positive mutation frequency in terms of specific growth rate reached 45% and 25%,
      respectively. The mutants in mutant library showed diverse phenotypes in terms of
      cell growth rate, carbohydrate content and flocculation intensity. The positive
      mutation frequency in terms of cellular carbohydrate content with the increase by
      more than 20% percent than the wild strain was 32.3%. Compared with the wild
      strain, the representative mutants 3-A10 and 3-B2 showed 40.3% and 78.0% increase
      in carbohydrate content, respectively, while the mutant 4-B3 showed 10.5%
      increase in specific growth rate. The carbohydrate contents of the representative
      mutants were stable during different subcultures, indicating high genetic
      stability. ARTP was demonstrated to be an effective and non-GMO mutagenesis tool
      to generate the mutant library for multicellular microalgae. 

PMID- 24319518
TI  - Ions Transport and Adsorption Mechanisms in Porous Electrodes During Capacitive
      Mixing Double Layer Expansion (CDLE).
AB  - A model of the electro-diffusion of ions in porous electrodes is applied to
      analyze the dynamics of capacitive-mixing extraction of energy from salinity
      gradients with carbon porous electrodes. The complex time-evolution of the cell
      voltage observed in experiments is satisfactorily described. The asymmetry on the
      duration of the solution-change steps performed in open circuit is found to be
      due to the nonlinear voltage-concentration relationship of the electric double
      layers and to a current that redistributes the counterions along the depth of the
      electrode leading to nonuniform charge and salt adsorption. The validated model
      is an essential tool for the design and optimization of renewable energy
      extraction by this technique.

PMID- 24319519
TI  - Effectiveness of electronic aids for smoking cessation.
AB  - Tobacco use continues to be the leading cause of preventable death in the world,
      and though current evidence-based approaches have substantially reduced rates of
      smoking, these rates remain disturbingly high. Two recent technological
      advancements, the electronic cigarette (e-cigarette) and mobile health (mHealth)
      interventions, may offer smokers an alternative way to quit smoking. E-cigarettes
      continue to be fiercely debated. Preliminary evidence suggests that e-cigarettes
      are likely much safer than regular cigarettes and are helpful to some smokers as
      a means of reducing or quitting smoking. Questions, however, still remain as to
      how they will affect overall public health-if they will be used as a "gateway"
      product or reduce motivation to quit smoking, to name but a few. Similarly,
      mHealth interventions appear to be effective and accepted by users. However,
      mobile 'apps' have yet to be tested in randomized trials and there are concerns
      about violations of users privacy and state jurisdictions.

PMID- 24319520
TI  - Three-dimensional spectral domain optical coherence tomography in Stargardt
      disease and fundus flavimaculatus.

PMID- 24319521
TI  - [Presentations of tuberculous adenitis of the head and neck at the University
      Hospital of Bobo-Dioulasso, Burkina Faso].

PMID- 24319522
TI  - [Particular evolution of complex cytogenetic variants of chronic myeloid leukemia
      treated with imatinib].

PMID- 24319524
TI  - [Pemphigus vegetans: a rare dermatosis of the folds].

PMID- 24319523
TI  - Validity of serum adenosine deaminase in diagnosis of tuberculosis.
AB  - INTRODUCTION: Tuberculosis is one of the most important infectious causes of
      death worldwide. Ziehl-Neelsen staining of sputum has high specificity in
      tuberculosis endemic countries, but modest sensitivity which varies among
      laboratories. This study was set up to investigate the diagnostic value of serum
      Adenosine deaminase in diagnosis of tuberculosis. METHODS: In a cross sectional
      and prospective study Serums of 200 patients of positive sputum smear, negative
      sputum smear, extra-pulmonary tuberculosis and bacterial community acquired
      pneumonia collected from March 2011 to May 2012 were evaluated. The data were
      analyzed using SPSS software and P-value of <0.05 was considered significant.
      RESULTS: A total of 200 subjects were included in the study designed in four
      groups. In cut-off value of >=24 U/l for ADA in smear positive patients defined
      the sensitivity, specificity and positive predictive value 12%, 98% and 86%
      respectively. In smear negative patients defined the 6%, 98% and 75%, and in
      extra-pulmonary tuberculosis patients defined the sensitivity 14%, 98% and 88%
      respectively. CONCLUSION: This study indicated that measurement of serum ADA
      level do not have enough sensitivity to assist in the diagnoses of tuberculosis
      patients from other respiratory diseases and not evaluated perform well enough to
      replace sputum smear microscopy. Thus, this tests have little role in the
      diagnosis of pulmonary tuberculosis.

PMID- 24319525
TI  - Correlation between dipstick urinalysis and urine sediment microscopy in
      detecting haematuria among children with sickle cell anaemia in steady state in
      Ilorin, Nigeria.
AB  - INTRODUCTION: Haematuria is one of the clinical manifestations of sickle cell
      nephropathy. Although dipstick urinalysis detects haemoglobin and by extension
      haematuria; it does not confirm haematuria. Urine sediment microscopy confirms
      haematuria and constitutes a non-invasive "renal biopsy". The need to correlate
      dipstick urinalysis and urine sediment microscopy findings becomes important
      because of the cheapness, quickness and simplicity of the former procedure.
      METHODS: Dipstick urinalysis and urine sediment microscopy were carried (both on
      first contact and a month after) among consecutive steady state sickle cell
      anaemia children attending sickle cell clinic at the University of Ilorin
      Teaching Hospital between October 2004 and July 2005. RESULTS: A total of 75
      sickle cell anemia children aged between 1-17 years met the inclusion criteria.
      Haematuria was found in 12 children (16.0%) and persistent haematuria in 10
      children 13.3%. Age and gender did not have significant relationship with
      haematuria both at first contact (p values 0.087 and 0.654 respectively) and at
      follow-up (p values 0.075 and 0.630 respectively). Eumorphic haematuria was
      confirmed in all the children with persistent haematuria with Pearson correlation
      +0.623 and significant p value of 0.000. CONCLUSION: The study has revealed a
      direct significant correlation for haematuria detected on dipstick urinalysis and
      at urine sediment microscopy. It may therefore be inferred that dipstick
      urinalysis is an easy and readily available tool for the screening of haematuria
      among children with sickle cell anaemia and should therefore be done routinely at
      the sickle cell clinics.

PMID- 24319526
TI  - Primary non-Hodgkin's lymphoma of the bladder: case report and literature review.
AB  - Primary non-Hodgkin's lymphoma (NHL) of the bladder is a very rare entity. The
      clinical, radiological and endoscopic signs are not specifics. The diagnosis is
      exclusively histological. Chemotherapy, radiotherapy and surgery are the
      different therapeutic options used either alone or in combination. We report a 57
      years old patient treated with chemotherapy (6 cycles of R-CHOP) for primary NHL
      of the bladder with a complete response while discussing the different
      specificities of this disease. 

PMID- 24319527
TI  - What is killing? People's knowledge about coronary heart disease, attitude
      towards prevention and main risk reduction barriers in Ismailia, Egypt
      (descriptive cross-sectional study).
AB  - INTRODUCTION: Cardiovascular diseases are a public health concern everywhere,
      especially ischemic or coronary heart diseases (CHD) which are on top of causes
      list of mortality and morbidity in both genders globally. From which nearly 80%
      can be because of modifiable risks. In Egypt, there is a lack of studies on the
      knowledge of people about coronary heart diseases and its modifiable risks. So,
      this research reported here we designed to measure the dimensions of peoples
      knowledge about CHD and their attitude towards prevention, and to identify the
      main risk reduction barriers. METHODS: By using comprehensive cross-sectional,
      descriptive research design, all adult individuals attending the family health
      clinic at Suez Canal University Hospital were eligible for inclusion with total
      number 125 participants. An interview questionnaire designed and used to collect
      data. RESULTS: The study revealed that (10.4%) of participants had a history of
      CHD, and (7.2%) had a family history of CHD. 79.2% Had a satisfactory total
      knowledge about CHD, and (94.4%) had a positive total attitude towards
      prevention. Risk reduction barriers as a medical setting barriers were (24%),
      patient related barriers were (22.4%). Community-societal barriers were almost
      the same as knowledge barriers which were around (16%). At last the systemic
      organizational barriers were (9.6%). CONCLUSION: The findings settled that, total
      knowledge about CHD was satisfactory but lower than the level total of attitude.
      More effort the health system needs to improve the settings and engage patients
      in their plans and breaking related barriers, with development of health
      education programs based on needs assessment. Further studies we recommend to
      explore the reasons and follow up the changes.

PMID- 24319528
TI  - Additive hazards regression and partial likelihood estimation for ecological
      monitoring data across space.
AB  - We develop continuous-time models for the analysis of environmental or ecological
      monitoring data such that subjects are observed at multiple monitoring time
      points across space. Of particular interest are additive hazards regression
      models where the baseline hazard function can take on flexible forms. We consider
      time-varying covariates and take into account spatial dependence via
      autoregression in space and time. We develop statistical inference for the
      regression coefficients via partial likelihood. Asymptotic properties, including
      consistency and asymptotic normality, are established for parameter estimates
      under suitable regularity conditions. Feasible algorithms utilizing existing
      statistical software packages are developed for computation. We also consider a
      simpler additive hazards model with homogeneous baseline hazard and develop
      hypothesis testing for homogeneity. A simulation study demonstrates that the
      statistical inference using partial likelihood has sound finite-sample properties
      and offers a viable alternative to maximum likelihood estimation. For
      illustration, we analyze data from an ecological study that monitors bark beetle
      colonization of red pines in a plantation of Wisconsin.

PMID- 24319529
TI  - Generalized seizures as the first manifestation of multihormonal pituitary
      hormone deficiency causing normovolemic hyponatremia.
AB  - PATIENT: Female, 14 FINAL DIAGNOSIS: Multiple pituitary hormone deficiency
      Symptoms: Hyponatremia Medication: - Clinical Procedure: Endovascular embolectomy
      Specialty: Endocrinology and Metabolic Objective: PATIENT complains/malpractice.
      BACKGROUND: Hyponatremia is one of the most common electrolyte disorders.
      Depending on the patient's hydration status, hyponatremia can be classified as
      hypovolemic, hypervolemic, or normovolemic. The last type is caused by the
      syndrome of 'inappropriate' secretion of antidiuretic hormone (SIADH), and more
      rarely by SIADH-like syndrome, in which oversecretion of ADH is caused by adrenal
      or thyroid insufficiency. CASE REPORT: This report presents the case of a girl
      who, at the age of 14 years and 4 months, presented with severe normovolemic
      hyponatremia (Na 110 mmol/L) due to decompensation of previously undiagnosed
      secondary adrenal insufficiency due to a respiratory tract infection.
      Hyponatremia was worsened by concomitant hypothyroidism and valproic acid
      therapy. This case is a rare example in clinical practice of multiple pituitary
      hormone deficiency, that despite typical symptoms such as short stature, adrenal
      insufficiency (hypoglycemia, hyponatremia, and low blood pressure), or delayed
      puberty, was diagnosed only after the development of adrenal crisis (severe
      symptomatic hyponatremia and hypoglycemia). CONCLUSIONS: In prepubertal pediatric
      patients with severe hyponatremia, multiple pituitary hormone deficiency must be
      considered. PATIENTs with hypothyroidism, as well as concomitant epilepsy treated
      with valproic acid, are at risk of severe hyponatremia, which may cause symptoms
      mimicking an epileptic attack.

PMID- 24319530
TI  - Minimally invasive enucleation with zero ischemia for malignancies. The Cluj
      Napoca experience.

PMID- 24319531
TI  - Malarial infection of female BWF1 lupus mice alters the redox state in kidney and
      liver tissues and confers protection against lupus nephritis.
AB  - Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease
      characterized by an imbalanced redox state and increased apoptosis. Tropical
      infections, particularly malaria, may confer protection against SLE. Oxidative
      stress is a hallmark of SLE. We have measured changes in the levels of nitric
      oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced
      glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an
      experimental model of SLE, after infection with either live or gamma-irradiated
      malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues
      after infection of lupus mice with live malaria. Similarly, the levels of NO and
      H2O2 were significantly decreased in the liver tissues of lupus mice after
      infection with live malaria. Conversely, GSH levels were obviously increased in
      both kidney and liver tissues after infection of lupus mice with either live or
      gamma-irradiated malaria. Liver and kidney functions were significantly altered
      after infection of lupus mice with live malaria. We further investigated the
      ultrastructural changes and detected the number of apoptotic cells in kidney and
      liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal
      that infection of lupus mice with malaria confers protection against lupus
      nephritis. 

PMID- 24319533
TI  - CLASSIFICATION OF TUMOR HISTOPATHOLOGY VIA SPARSE FEATURE LEARNING.
AB  - Our goal is to decompose whole slide images (WSI) of histology sections into
      distinct patches (e.g., viable tumor, necrosis) so that statistics of distinct
      histopathology can be linked with the outcome. Such an analysis requires a large
      cohort of histology sections that may originate from different laboratories,
      which may not use the same protocol in sample preparation. We have evaluated a
      method based on a variation of the restricted Boltzmann machine (RBM) that learns
      intrinsic features of the image signature in an unsupervised fashion. Computed
      code, from the learned representation, is then utilized to classify patches from
      a curated library of images. The system has been evaluated against a dataset of
      small image blocks of 1k-by-1k that have been extracted from glioblastoma
      multiforme (GBM) and clear cell kidney carcinoma (KIRC) from the cancer genome
      atlas (TCGA) archive. The learned model is then projected on each whole slide
      image (e.g., of size 20k-by-20k pixels or larger) for characterizing and
      visualizing tumor architecture. In the case of GBM, each WSI is decomposed into
      necrotic, transition into necrosis, and viable. In the case of the KIRC, each WSI
      is decomposed into tumor types, stroma, normal, and others. Evaluation of 1400
      and 2500 samples of GBM and KIRC indicates a performance of 84% and 81%,
      respectively.

PMID- 24319532
TI  - Accelerated aging during chronic oxidative stress: a role for PARP-1.
AB  - Oxidative stress plays a major role in the pathophysiology of chronic
      inflammatory disease and it has also been linked to accelerated telomere
      shortening. Telomeres are specialized structures at the ends of linear
      chromosomes that protect these ends from degradation and fusion. Telomeres
      shorten with each cell division eventually leading to cellular senescence.
      Research has shown that poly(ADP-ribose) polymerase-1 (PARP-1) and subtelomeric
      methylation play a role in telomere stability. We hypothesized that PARP-1 plays
      a role in accelerated aging in chronic inflammatory diseases due to its role as
      coactivator of NF-kappab and AP-1. Therefore we evaluated the effect of chronic
      PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured
      under normal conditions and under conditions of chronic oxidative stress, induced
      by tert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under
      normal culturing conditions accelerated the rate of telomere shortening. However,
      under conditions of chronic oxidative stress, PARP-1 inhibition did not show
      accelerated telomere shortening. We also observed a strong correlation between
      telomere length and subtelomeric methylation status of HF cells. We conclude that
      chronic PARP-1 inhibition appears to be beneficial in conditions of chronic
      oxidative stress but may be detrimental under relatively normal conditions.

PMID- 24319534
TI  - Evaluation of the effect of genetic variation on the relationship between
      statins, cardiovascular disease and cancer.
AB  - Statins are a class of medications that are competitive inhibitors of Hydroxy
      Methyl Glutaryl Co-enzyme A (HMG-CoA) reductase which is the rate-limiting enzyme
      in the cholesterol bio-synthesis pathway. As a result, statins lower total
      cholesterol and low density lipoprotein (LDL) cholesterol thus impacting
      cardiovascular mortality. The downstream effects of statins are not limited to
      inhibition of cholesterol synthesis alone. Statins have anti-inflammatory effects
      thought to be important in the setting of acute myocardial infarction which also
      may be a mechanism involved in anti-carcinogenic properties of statins.
      Furthermore, statin inhibition of the mevalonate pathway may impact Ras and
      RhoGTPases that are important in cell proliferation, migration and apoptosis.
      These alterations may also play a role in the anti-cancer effect of statins. In
      this article we will review the literature on how genetic variation modifies the
      effect of statins on the risk of cardiovascular disease and how genetic variation
      may impact the relationship between statins and the risk of a number of different
      cancers. 

PMID- 24319535
TI  - Fine mapping of variants associated with endometriosis in the WNT4 region on
      chromosome 1p36.
AB  - Genome-wide association studies show strong evidence of association with
      endometriosis for markers on chromosome 1p36 spanning the potential candidate
      genes WNT4, CDC42 and LINC00339. WNT4 is involved in development of the uterus,
      and the expression of CDC42 and LINC00339 are altered in women with
      endometriosis. We conducted fine mapping to examine the role of coding variants
      in WNT4 and CDC42 and determine the key SNPs with strongest evidence of
      association in this region. We identified rare coding variants in WNT4 and CDC42
      present only in endometriosis cases. The frequencies were low and cannot account
      for the common signal associated with increased risk of endometriosis. Genotypes
      for five common SNPs in the region of chromosome 1p36 show stronger association
      signals when compared with rs7521902 reported in published genome scans. Of
      these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA
      sequences with potential functional roles including overlap with transcription
      factor binding sites for FOXA1, FOXA2, ESR1, and ESR2. Functional studies will be
      required to identify the gene or genes implicated in endometriosis risk. 

PMID- 24319537
TI  - Common sequence variants in chemokine-related genes and risk of breast cancer in
      post-menopausal women.
AB  - Chemokines are small molecules that when secreted by tissues under pathological
      conditions such as inflammation are believed to be involved in carcinogenesis.
      Recent reports have found that the genetic variation in chemokine encoding genes
      are associated with risk of breast cancer. METHODS: Using data from a population
      based case-control study of 845 invasive breast cases and 807 controls, we
      genotyped 34 single nucleotide polymorphisms (SNPs) in 8 chemokine candidate
      genes (CCL3, CCL4, CCL5, CCL20, CCR5, CCR6, CXCL12 and CXCR4). Associations with
      breast cancer were computed for individual SNPs, groups of SNPs within genes, and
      in a gene-set analysis. We also performed a meta-analysis of CXCL12 rs1801157 and
      a haplotype analysis for two SNPs: CXCR4 rs2228014 and CXCL12 rs1801157. RESULTS:
      We found no significant associations between the risk of breast cancer and any
      individual SNPs, single genes, or combined gene sets. Some individual variants
      were marginally associated with some histologic subtypes, but these associations
      were not significant after adjustment for multiple comparisons. In the meta
      analysis of five studies of European ancestry, CXCL12 rs1801157 was marginally
      associated with breast cancer risk (OR=1.14, 95% CI: 1.00, 1.30). CONCLUSIONS:
      Our findings suggest that genetic variants in the 8 candidate genes coding for
      chemotactic cytokines have little influence in the risk of breast cancer in
      postmenopausal women. Additional examination of the relationship between CXCL12
      rs1801157 and breast cancer risk is warranted.

PMID- 24319536
TI  - CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population.
AB  - Urinary bladder cancer incidence in Lebanon ranks among the highest in the world.
      Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N
      Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the
      metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated
      in bladder cancer. The present study attempts to investigate the role of these
      DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and
      106 controls were recruited from two hospitals in Beirut. An interview-based
      questionnaire was administered to assess suspected environmental and occupational
      risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs
      genotypes. Associations between bladder cancer and putative risk factors were
      measured using adjusted odds ratios (ORs) and their 95% confidence intervals
      (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for
      bladder cancer. No significant differences in frequency distribution of the NQO1
      genotypes were found in cases versus controls. The odds of carrying the CYP2E1
      c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95%
      CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times
      higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study
      suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for
      bladder cancer in Lebanese. Further studies with larger samples must be conducted
      to confirm these findings. 

PMID- 24319538
TI  - LHRH and LHR genotypes and prostate cancer incidence and survival.
AB  - Despite their crucial role in initiating steroid-hormone synthesis, the
      hypothalamic and pituitary hormones (LH, LHRH) and their receptors have received
      scant attention in genetic studies of hormone-related diseases. This study
      included 1,170 men diagnosed with prostate cancer (PC) in Los Angeles County
      between 1999 and 2003. LHRH and LH receptor genotypes were examined for
      association with PC survival. Additionally, associations with PC incidence were
      examined by comparing PC cases to control men of similar age and race/ethnicity.
      The LHR 312 G allele was found to be associated with increased PC mortality
      (p=0.01). Ten years after diagnosis, 16% of men carrying two copies of the G
      allele (genotype GG) had died of PC, compared to 11% of those with genotype AG
      and 9% of those with AA. In a case-control comparison, this same allele was
      significantly associated with decreased PC risk: OR=0.68 (95% CI: 0.49, 0.93) for
      genotype GG vs. AA. These results suggest that androgens may play opposing roles
      in PC initiation and progression, and highlight the need to include these
      important but overlooked genes in future studies of PC etiology, prognosis, and
      treatment. 

PMID- 24319539
TI  - Epidermal growth factor receptor (EGFR) polymorphisms and breast cancer among
      Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities
      Study.
AB  - The epidermal growth factor receptor (EGFR), a member of the ErbB family of
      receptor tyrosine kinases, functions in cellular processes essential to the
      development of cancer. Overexpression of EGFR in primary breast tumors has been
      linked with poor prognosis. We investigated the associations between 34 EGFR
      tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703
      Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health
      Disparities Study. We evaluated associations with risk of breast cancer defined
      by estrogen/progesterone receptor (ER/PR) tumor phenotype. Only one association
      remained statistically significant after adjusting for multiple comparisons.
      Rs2075112GA/AA was associated with reduced risk for ER-/PR+ tumor phenotype (odds
      ratio (OR), 0.34; 95% confidence interval (CI) 0.18-0.63, p adj=0.01). All
      additional results were significant prior to adjustment for multiple comparisons.
      Two of the EGFR polymorphisms were associated with breast cancer risk in the
      overall study population (rs11770531TT: OR, 0.56, 95% CI 0.37-0.84; and
      rs2293348AA: OR, 1.20, 95% CI 1.04-1.38) and two polymorphisms were associated
      with risk among Hispanics: rs6954351AA: OR, 2.50, 95% CI 1.32-4.76; and
      rs845558GA/AA: OR, 1.15, 95% CI 1.01-1.30. With regard to breast cancer-specific
      mortality, we found positive associations with rs6978771TT hazard ratio (HR),
      1.68; 95% CI 1.11-2.56; rs9642391CC HR, 1.64; 95% CI 1.04-2.58; rs4947979AG/GG
      HR, 1.36; 95% CI 1.03-1.79; and rs845552GG HR, 1.62; 95% CI 1.05-2.49. Our
      findings provide additional insight for the role of EGFR in breast cancer
      development and prognosis. Further research is needed to elucidate EGFR's
      contribution to ethnic disparities in breast cancer. 

PMID- 24319540
TI  - Intrafamilial spread of hepatitis B virus in Guilan Province-North of Iran.
AB  - The aim of the present study was to determine the intrafamilial spread of HBV in
      the family members of patients with Hepatitis B in Guilan Province, North of
      Iran. In a descriptive-comparative study, 156 patients with Hepatitis B, 415
      family members of the index cases and 599 age and gender matched people as a
      control group were enrolled. Blood samples were taken from the participants and
      were checked for HBs Ag, HBC Ab, HBs Ab, and HBV DNA. Totally 44 (10.6%) of
      family members and only 1 (0.2%) of control group were HBs Ag positive (P=0.0001,
      OR=70.92). The overall prevalence in members of the original family was 5.3%
      (1.2% of the mothers, 2.2% of the brothers, 1.9% of the sisters), in sexual
      partners it was 1.4%, in offsprings it was 2.4% and in other households it was
      1.4%. The mean age of HBs Ag positive family members was 35.3 +/- 12.9 years old.
      Among them 27 (61.4%) were female. Only 8 (18.2%) of all HBsAg-positive reported
      previous HBV vaccination but just one person had the vaccine titer checked. The
      present survey indicates that there is a significant difference in the prevalence
      of Hepatitis B in the general population and family members of Hepatitis B
      patients and this is an evidence for horizontal transmission of HBV in household
      contacts. 

PMID- 24319541
TI  - Association of SERPINA9 gene variants with carotid artery atherosclerosis: the
      Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.
AB  - The SNP rs11628722 in the SERPINA9 gene was previously associated with incident
      ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.
      Centerin, the protein encoded by SERPINA9, is involved in maturation and
      maintenance of naive B cells, which play a role in atherogenesis. We investigated
      whether 21 tag SNPs in the SERPINA9 gene are associated with features of carotid
      artery atherosclerotic plaque measured by magnetic resonance imaging (MRI).
      Carotid MRI data were obtained from 1,282 European Americans and 341 African
      Americans of the ARIC Carotid MRI study, which recruited participants from ARIC
      by a stratified sampling plan that over-sampled participants with carotid intima
      media thickening. Five MRI measures, focused on carotid wall volume, wall
      thickness, and lipid core, were analyzed. Genetic associations between the MRI
      measurements and each of the 21 SNPs were analyzed in linear regression models
      with adjustment for sample weights and traditional risk factors. Rs11628722 was
      tested a priori. In African Americans, rs11628722 was significantly associated
      with carotid wall volume (p < 0.05). Among the other 20 SNPs, adjusted for
      multiple testing, rs4905204, which encodes an Ala to Val amino acid change, was
      significantly associated with maximum wall thickness (p < 0.000625) and
      suggestively associated with total wall volume (p < 0.0026) in European
      Americans. In conclusion, SNPs in the SERPINA9 gene showed race-specific
      associations with characteristics of carotid atherosclerotic plaques.
      Replications in other populations are needed to validate findings of this study
      and to establish the SERPINA9 gene as a candidate in the etiology of carotid
      atherosclerosis. 

PMID- 24319542
TI  - In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs).
AB  - RNA interference (RNAi) has considerable potential as a therapeutic strategy, but
      the development of efficient in vivo RNA delivery methods remains challenging. To
      this end, we designed and synthesized chemically modified interfering
      nanoparticles (iNOPs) composed of functionalized poly-l-lysine dendrimers
      modified with reducible spacers to facilitate release of small interfering RNAs
      (siRNAs) in vivo. We show that the novel siRNA-iNOP complexes mediate efficient
      gene-specific RNAi in cultured cells and in mice, where they display enhanced
      tissue-targeting capabilities. At a clinically feasible dose of 1 mg kg-1,
      apolipoprotein B (apoB) siRNA-iNOP complexes achieved ~40-45% reduction of liver
      apoB mRNA and plasma apoB protein levels within 48 h of administration to mice,
      without apparent toxicity. Collectively, these findings demonstrate that siRNA
      delivery by the modified reducible iNOPs can provide a clinically significant and
      potentially tissue-specific new approach for RNAi therapy.

PMID- 24319543
TI  - C-6 Ceramide Induces p53 Dependent Apoptosis in Human Astrocytoma Grade4
      (Glioblastoma Multiforme) Cells.
AB  - Ceramide is composed of sphingosine and a fatty acid found in large concentration
      within the cell membrane and often acts as a signaling molecule for various
      functions including programmed cell death. In the present investigation, we
      observed that C6-ceramide induces p53-dependent apoptosis and effectively killed
      the Astrocytoma grade4 (Glioblastoma Multiforme) HTB12 cell lines. Ceramide
      induced cell death was confirmed by Trypan blue assay which showed about 65%
      cells dying from ceramide treatment. Apoptosis was confirmed by Caspase3 ELISA
      assay and DNA fragmentation assay. The p53 induction was confirmed by immunoblot
      studies. Since C6 Ceramide induces apoptosis in Glioblastoma cells, it may be
      employed in chemotherapeutic strategy to treat this highly malignant brain
      cancer.

PMID- 24319544
TI  - Human Breast Cancer Stem Cells Have Significantly Higher Rate of Clathrin
      Independent and Caveolin-Independent Endocytosis than the Differentiated Breast
      Cancer Cells.
AB  - Breast Cancer Stem (BCS) cells play critical roles in self-renewal, Multi Drug
      Resistance (MDR), differentiation and generation of secondary tumors.
      Conventional chemotherapy may efficiently kill the bulk of differentiated drug
      sensitive breast cancer cells, but not the MDR self-renewable BCS cells, leading
      to enrichment of the MDR BCS cells. In order to target the MDR BCS cells, we have
      isolated: 1) BCS cells from either breast cancer cell lines or fresh breast
      cancer specimens; 2) ATP binding cassette (ABC) transporter group G number 2
      (ABCG2)-specific aptamers; and 3) BCS cell-binding aptamers. Interestingly, ABCG2
      specific aptamers labeled the membrane surface of the ABCG2-expressing baby
      hamster kidney (BHK) cells, but stained whole cells of the BCS cells derived from
      mammospheres, implying that BCS cells might have much higher rate of endocytosis
      than the ABCG2-expressing BHK cells. In addition, 5D3, a monoclonal antibody that
      recognizes the extracellular loops of ABCG2 protein, also stained whole BCS
      cells. Furthermore, BCS cell-binding aptamers stained whole BCS cells, but not
      the differentiated breast cancer MCF-7 cells. All these results support above
      conclusion that BCS cells might have high rate of endocytosis. Further
      experiments performed with aptamers and human transferrin or lactosylceramide
      showed that BCS cells do have much higher endocytosis rate than the
      differentiated breast cancer cells. Interestingly, clathrin dependent endocytosis
      inhibitors, such as monodansylcadaverine or sucrose, or caveolin-dependent
      endocytosis inhibitors, such as methyl-beta-cyclodextrin or genistein, can
      inhibit the internalization of transferrin or lactosylceramide into the
      differentiated breast cancer cells, but cannot block the internalization of these
      compounds into the BCS cells, suggesting that BCS cells undergo clathrin
      independent and caveolin-independent endocytosis. Taken together, our data
      suggest that BCS cells have high rate of endocytosis and open the possibilities
      for delivering therapeutic agents directly into the MDR BCS cells with aptamer
      coated liposomes.

PMID- 24319545
TI  - Variation in the Effect of Communities That Care on Community Adoption of a
      Scientific Approach to Prevention.
AB  - Tested and effective approaches are available to prevent mental, emotional, and
      behavioral problems in youth, but such approaches are underused. Communities That
      Care (CTC) is a coalition-based strategy that aims to increase the use of tested
      and effective programs by combining the use of scientific evidence and
      stakeholder consensus to support the community adoption of a scientific approach
      to preventing mental, emotional, and behavioral problems in youth. A community
      randomized trial of CTC was conducted with a sample of 24 communities matched in
      pairs and assigned randomly to a control or an intervention condition. The
      findings demonstrate that CTC significantly increases the community-wide adoption
      of a science-based approach to prevention. Using a meta-analysis technique, this
      study shows that despite uniformly high-fidelity implementation of CTC in
      intervention communities, the effect of CTC on the adoption of a scientific
      approach to prevention varies significantly across the 12 community pairs.
      Understanding the extent of variation in the effect of CTC on adopting a science
      based approach to prevention lays a foundation for identifying aspects of
      coalition structure, functioning, or capacity that not only may help explain
      variation in adoption, but may in turn be targeted to strengthen the effect of
      CTC on the adoption of a science-based approach to prevention within communities.

PMID- 24319546
TI  - Appetite control and gastrointestinal hormonal behavior (CCK, GLP-1, PYY 1-36)
      following low doses of a whey protein-rich nutraceutic.
AB  - Whey proteins represent the most satiating nutrients. In particular, their
      effects are due to enterohormonal changes (CCK, GLP-1 and PYY 1-36) observed
      after their exclusive ingestion. Glucomannan has important satiety property due
      to volume increase following gelification. The aim of the study is the evaluation
      of subjective rate of hunger and enterohormone concentrations (CCK, GLP-1, PYY 1
      36) following oral loading of a mixture containing WP (8 g) or casein (8 g) plus
      glucomannan (1 g) (Colordiet(r), Inpha DUEMILA Srl Lecco, Italy). The study was
      conducted as a double-blind crossover with five healthy volunteers (BMI 22-26
      kg/m2 aging 18-65 years) in acute and a wash-out period of 1 week between the
      first and the second evaluation. From the analysis of the data, we observe that
      the load with WP induces a significant decrease in the desire to eat after 90 min
      (P < 0.0446) when compared with casein. As far as plasma hormones are concerned,
      there was a significant increase only in GLP-1 at 90 min after WP (P < 0.00166)
      and 180 min after casein (T0 vs. T180 P = 0.000129). There is a significant
      correlation between the increase in GLP-1 and decrease of desire to eat (R = 
      0.93). There is a tendency to the increasing of CCK after 90 min, which is not
      significant (P = 0.091). These results could be due to (a) the low number of
      cases or (b) the low dose of protein used. The present study suggests that a
      mixture of WP plus glucomannan exerts a decrease in the desire to eat which is
      correlated to enterohormonal modification (GLP-1 increase) despite the low
      content of protein (8 g) and the presence of glucomannan, which could reduce the
      fast absorption of WP in relation to the net forming during the gelification of
      the gastric environment.

PMID- 24319548
TI  - National program of health-care for the elderly in India: a hope for healthy
      ageing.

PMID- 24319547
TI  - A concise review of carbon nanotube's toxicology.
AB  - Carbon nanotubes can be either single-walled or multi-walled, each of which is
      known to have a different electron arrangement and as a result have different
      properties. However, the shared unique properties of both types of carbon
      nanotubes (CNT) allow for their potential use in various biomedical devices and
      therapies. Some of the most common properties of these materials include the
      ability to absorb near-infra-red light and generate heat, the ability to deliver
      drugs in a cellular environment, their light weight, and chemical stability.
      These properties have encouraged scientists to further investigate CNTs as a tool
      for thermal treatment of cancer and drug delivery agents. Various promising data
      have so far been obtained about the usage of CNTs for cancer treatment; however,
      toxicity of pure CNTs represents a major challenge for clinical application.
      Various techniques both in vivo and in in vitro have been conducted by a number
      of different research groups to establish the factors which have a direct effect
      on CNT-mediated cytotoxicity. The main analysis techniques include using Alamar
      blue, MTT, and Trypan blue assays. Successful interpretation of these results is
      difficult because the CNTs can significantly disrupt the emission of the certain
      particles, which these assays detect. In contrast, in vivo studies allow for the
      measurement of toxicity and pathology caused by CNTs on an organismal level.
      Despite the drawbacks of in vitro studies, they have been invaluable in
      identifying important toxicity factors, such as size, shape, purity, and
      functionalisation, the latter of which can attenuate CNT toxicity. 

PMID- 24319549
TI  - Meta-Analysis of Prevalence of Smoking in 15-64-year-old Population of West of
      Iran.
AB  - BACKGROUND: Cigarette Smoking is a recognized cause of systemic disorders such as
      bronchogenic, carcinoma, and cardiovascular diseases and hence prompt and
      effective interventions are required for its elimination. Thus, This Meta
      analysis was carried out for an adult population of west of Iran in order to
      estimate of prevalence smoking in this area. METHODS: We examined related to
      documentation by searching in published and non-electronic databases. Data were
      extracted based on variables such as the year of the study, sex, age group, and
      the prevalence of smoking. Based on the results of heterogeneity, we used fixed
      or random effects model to assessment the overall prevalence of cigarette
      smoking. All analyses were accomplished via STATA 11 software. RESULTS: Totally,
      25,990 subjects (13005 males) were investigated. Meta-analysis in men and women
      indicated prevalence of 22.9 (20.6-25.2) and 0.6 (0.3-0.9) respectively.
      CONCLUSIONS: It was found that more than one-fifth of men from 15 year to 64-year
      old of west of Iran smoked cigarette. Providing an education on harmful effects
      of smoking to the adult population would be a valuable means for reducing
      destructive consequences of smoking.

PMID- 24319550
TI  - The Relationship between Trait Anxiety and Driving Behavior with Regard to Self
      reported Iranian Accident Involving Drivers.
AB  - BACKGROUND: THE AIMS OF THIS STUDY INCLUDED: Determination of the most common
      driver behavior in drivers and also analyzing the relationship between trait
      anxiety (TA) with subscale of driving behavior (lapses, errors, ordinary and
      aggressive violations). METHODS: This cross-sectional study was conducted on 168
      drivers that having crash. The self-reporting of the drivers was determined by
      using Manchester driving behavior questionnaire (DBQ) and Spielberger State-Trait
      Anxiety Inventory. RESULTS: Independent t-test showed that violations factor
      (ordinary and aggressive) are the most common behavior in drivers, Pearson
      correlation revealed that TA had a significant direct positive relation with all
      DBQ subscales especially error and lapses factor (P < 0.01) also Pearson
      correlation showed that age had a negative significant relation with factors of
      DBQ. CONCLUSIONS: It can be concluded from the results (according to the relation
      between TA with error and lapses factor) that the rate of TA is destructive
      effective on the memory performance and process in the drivers and cause absent
      minded and memory imperfect function and process in these people during the
      driving.

PMID- 24319551
TI  - The Spatial Distribution of Cancer Incidence in Fars Province: A GIS-Based
      Analysis of Cancer Registry Data.
AB  - BACKGROUND: Cancer is a major health problem in the developing countries.
      Variations of its incidence rate among geographical areas are due to various
      contributing factors. This study was performed to assess the spatial patterns of
      cancer incidence in the Fars Province, based on cancer registry data and to
      determine geographical clusters. METHODS: In this cross sectional study, the new
      cases of cancer were recorded from 2001 to 2009. Crude incidence rate was
      estimated based on age groups and sex in the counties of the Fars Province. Age
      standardized incidence rates (ASR) per 100,000 was calculated in each year.
      Spatial autocorrelation analysis was performed in measuring the geographic
      patterns and clusters using geographic information system (GIS). Also,
      comparisons were made between ASRs in each county. RESULTS: A total of 28,411 new
      cases were diagnosed with cancer during 2001-2009 in the Fars Province, 55.5% of
      which were men. The average age was 61.6 +/- 0.5 years. The highest ASR was
      observed in Shiraz, which is the largest county in Fars. The Moran's Index of
      cancer was significantly clustered in 2004, 2005, and 2006 in total, men, and
      women. The type of spatial clustering was high-high cluster, that to indicate
      from north-west to south-east of Fars Province. CONCLUSIONS: Analysis of the
      spatial distribution of cancer shows significant differences from year to year
      and between different areas. However, a clear spatial autocorrelation is
      observed, which can be of great interest and importance to researchers for future
      epidemiological studies, and to policymakers for applying preventive measures.

PMID- 24319552
TI  - Brewer's Yeast Improves Glycemic Indices in Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Brewer's yeast may have beneficial effects on insulin receptors
      because of itsglucose tolerance factor in diabetic patients. This study was
      conducted to investigate the effects of brewer's yeast supplementation on
      glycemic indices in patients with type 2 diabetes mellitus. METHODS: In a
      randomized double-blind controlled clinical trial, 84 adults (21 men and 63
      women) aged 46.3 +/- 6.1 years old with type 2 diabetes mellitus were recruited
      and divided randomly into two groups: Supplement group receiving brewer's yeast
      (six 300mg tablets/day, total 1800 mg) and control group receiving placebo (six
      300mg tablets/day) for 12 weeks. Body weight, height, body mass index, food
      consumption (based on 24h food record), fasting blood sugar (FBS), glycosylated
      hemoglobin, insulin sensitivity, and insulin resistance were measured before and
      after the intervention. Data analysis was performed using the Statistical Package
      for Social Sciences (version 18.0). RESULTS: The changes in FBS, glycosylated
      hemoglobin, and insulin sensitivity were significantly different between the two
      groups during the study (respectively P < 0.001, P < 0.001, P = 0.02 independent
      sample t-test). There was a significant difference in FBS, glycosylated
      hemoglobin, and insulin sensitivity at the end of the study between the two
      groups after removing the effects of baseline values (respectively P = 0.002, P <
      0.001, P = 0.02, analysis of covariance). Changes in body mass index, 24h food
      record, insulin resistance were not significant. CONCLUSIONS: Dietary
      supplementation with brewer>s yeast besides the usual treatment of diabetes can
      ameliorate blood glucose variables in type 2 diabetes mellitus.

PMID- 24319553
TI  - N-acetylcysteine Prevents Kidney and Lung Disturbances in Renal
      Ischemia/Reperfusion Injury in Rat.
AB  - BACKGROUND: One of the most common causes of acute kidney injury (AKI) is kidney
      ischemia/reperfusion injury (IRI). The distant organ injury such as acute lung
      injury is one of the side effects of AKI or kidney IRI. In this study, we
      performed bilateral renal IRI in rats and the protective role of N-acetylcysteine
      (NAC) in kidney and lung was investigated. METHODS: Rats (n = 30) were randomly
      assigned to four experiment groups. The group 1 was assigned as sham-operated
      group. Before kidney IRI performance, the others groups were treated with saline
      (group 2), 150 mg/kg (group 3) or 500 mg/kg (group 4) of NAC, and the treatment
      were continued daily after IRI for next 3 days. At day 3, the all groups' animals
      were subjected for the measurements. RESULTS: The serum level of blood urea
      nitrogen (BUN) and creatinine (Cr) in the control group increased significantly
      (P < 0.05), and administration of NAC (150 mg/kg) decreased the serum levels of
      Cr and BUN. However, only the serum level of Cr decreased significantly (P <
      0.05). NAC did not improve kidney weight and damage; however, its low dose (150
      mg/kg) attenuated the lung injury score (P < 0.05) when compared with the control
      group. No significant differences were observed in lung water content and
      endothelial permeability, serum levels of malondialdehyde and nitrite between the
      groups. CONCLUSIONS: Low dose of NAC as a protectant agent may protect the kidney
      function and lung tissue damage after kidney IRI.

PMID- 24319554
TI  - Cardiac Strain between Normal Weight and Overweight Workers in Hot/Humid Weather
      in the Persian Gulf.
AB  - BACKGROUND: In hot weather, overweight and obesity are considered as significant
      risk factors for the incidence of cardiac strain in workers. This study was aimed
      to compare cardiac strain among overweight and normal-weight workers in hot,
      humid conditions in the south of Iran. METHODS: This cross-sectional study was
      conducted on 71 workers in the south of Iran in summer 2010. The heart rate was
      measured at rest and at actual work. Cardiac strain based on working heart rate
      (WHR), the relative cardiac cost (RCC), the net cardiac cost (NCC), load relative
      cardiovascular (CVL), and heart rate reduction was analyzed in 35 normal-weight
      people (body mass index (BMI) <25 kg/m(2)) and 36 overweight people (BMI >25
      kg/m(2)) using descriptive statistics. RESULTS: In 42% of the total workers, BMI
      was >25 kg/m(2). The average of Wet Bulb Globe Temperature Index (WBGT Index) in
      the two groups was not significantly different. The mean WHR in the two groups
      was 101 +/- 20.3 and 112 +/- 18.9, respectively (P = 0.026). Percentages exceeded
      the acceptable limits in the parameters NCC, RCC, WHR, CVL, and Brouha index,
      which were significantly higher in overweight people than in those with normal
      weight. CONCLUSIONS: Based on the study results, it is concluded that the
      severity of cardiac strain was higher in overweight workers compared with that in
      normal weight workers. Hence, in order to decrease the cardiac strain, selecting
      overweight individuals for these jobs should be avoided and also some vital
      intervention for losing weight should be implemented such as nutrition education
      and encouraging them regarding physical activity.

PMID- 24319555
TI  - Comparing Tobacco Use Knowledge, Attitudes and Practices between Engineering
      Students at a Public and Islamic Azad University in Shiraz, Iran 2011.
AB  - BACKGROUND: To compare the level of knowledge, the attitudes, and practices with
      regards to tobacco use between Iranian students at a public (PBU) and Islamic
      Azad (IAU) university. METHODS: A cross-sectional design was used in this study.
      As the number of students at the IAU were three times greater than that of the
      PBU, we selected 150 students from the PBU and 450 students from the IAU using
      simple random sampling. A 57-item survey instrument was utilized for this study.
      The collected data were recorded by SPSS version 15 software and then it
      underwent statistical analysis using descriptive statistics and ANOVA to compare
      the difference between means of knowledge, attitude and practice scores. Logistic
      regression analysis was conducted to identify variables that have an independent
      association with students smoking and to describe possible variations in these
      relationships. The P value level for statistical significance was set at 0.05.
      RESULTS: From participants, 46.8% were females, 10% of 327 students reported
      being daily smokers; of these, 84% were from the IAU. Totally, among the 107
      smokers, 61 (57%) and 29 (27.1%) were water pipe and cigarettes smokers,
      respectively. Ninety-three IAU students (21.7%) and 30 PBU students (20.7%)
      reported smoking during the past 30 days. The mean of the knowledge items between
      the students of IAU was lower than PBU students. Female gender, smoking in the
      home, and allowing visitors to smoke in the home were significant predictors of
      smoking in the past 30 days in PBU, respectively. In IAU, female gender, smoking
      by friends, and health status were predictors for smoking in the past 30 days.
      CONCLUSIONS: Future studies should assess the factors affecting smoking
      initiation, as well as effective techniques for the prevention of smoking
      initiation and substance abuse in Iranian adolescents and young adults.

PMID- 24319556
TI  - Clinical Effectiveness of Co-trimoxazole vs. Amoxicillin in the Treatment of Non
      Severe Pneumonia in Children in India: A Randomized Controlled Trial.
AB  - BACKGROUND: Acute respiratory infection (ARI) in young children is responsible
      for an estimated 4.1 million deaths worldwide of which approximately 90% are due
      to pneumonia. To study the clinical effectiveness of co-trimoxazole versus
      amoxicillin in the treatment of non-severe pneumonia, as defined by WHO, in
      children in the age group of 02 months to 5 years. Randomized Control Trial study
      was conducted in out patient department of a large tertiary care hospital after
      taking consent from parents and ethical committee clearance. METHODS: Children in
      study group were treated with amoxicillin (40 mg/kg/day in 3 divided doses) and
      those in control group were treated with co-trimoxazole (8 mg/kg/day of
      trimethoprim in 2 divided doses). All cases were reviewed on second and fifth
      day. The effectiveness and therapy failure were decided on the basis of clinical,
      radiological and complete blood count results. RESULTS: Two hundred and four
      cases of non severe pneumonia were studied. All cases were diagnosed on the basis
      of clinical criteria, as defined by WHO. Treatment failure was seen in 8.09%
      cases with amoxicillin and 39.05% cases with co-trimoxazole. Cost of one complete
      course with amoxicillin was 2.3 times higher than with co-trimoxazole. Compliance
      of therapy to co-trimoxazole (90.47%) was better than to amoxicillin (83.84%).
      CONCLUSIONS: The response to treatment with amoxicillin is faster, however,
      compliance is slightly poorer and cost of treatment high. In order to improve the
      compliance, better counseling and more studies are required to ascertain the
      efficacy of amoxicillin in higher dosage over a shorter period of time.

PMID- 24319557
TI  - Can Sex-hormone Binding Globulin Considered as a Predictor of Response to
      Pharmacological Treatment in Women with Polycystic Ovary Syndrome?
AB  - BACKGROUND: This study aims to evaluate the sex hormone binding globulin (SHBG)
      level as a predictor of response to pharmacological treatment in women with
      polycystic ovary syndrome (PCOS). METHODS: This study was conducted in 2009-2012
      in Isfahan, Iran. Anovulatory women with a diagnosis of PCOSwere studied.
      Metformin was started at 500 mg three times a day. If no ovulation occurred,
      Clomiphene citrate was added. RESULTS: The study comprised273 infertile women
      with PCOS completed the study, 75 (28%) of them became pregnant 6 months after
      treatment (7.36% with metformin and 20.14% with metformin and clomiphene
      citrate). Patients who responded to metformin treatment had significantly lower
      mean SHBG levels compared to those who did not (0.88+0.32vs. 0.2642+0.44 nmol/L,
      respectively, P<0.0001). The area under the ROC curve (AUC) for prediction the
      response to treatment was 0.85. The baseline level of 27was the most appropriate
      cut of point HSBG for the prediction of conception. HSBG had a sensitivity of
      88%, and specificity of 73.6%. It had a false positive level of 26.4% and false
      negative level of 12%. Its positive predictive value was 56.4% and its negative
      predictive value was 94%. The chance of conception increased for reducing a unit
      of fpg (OR = 0.69; 95% CI = 0.54-0.86; P = .002), as well as reducing of every
      unit of HSBG (OR = 0.47; 95% CI = 0.39-0.56; P <0.001), and for reducing each
      unit of insulin in (OR = 0.082; 95% CI = 1.021-0.33; P <0.001). CONCLUSION: HSBG
      test is suggested as an appropriate test for predicting pregnancy achievement of
      PCOs women after pharmacological treatment.

PMID- 24319558
TI  - Is alcohol consumption associated with poor academic achievement in university
      students?
AB  - BACKGROUND: We assessed associations between educational achievement and alcohol
      consumption. METHODS: We employed five alcohol consumption measures (length of
      time of and amount consumed during most recent drinking occasion, frequency of
      alcohol consumption, heavy episodic drinking, problem drinking); and three
      educational achievement indicators (students' subjective importance of achieving
      good grades, students' appraisal of their academic performance in comparison with
      peers, students' actual module mark). RESULTS: Males were positively associated
      with all five alcohol consumption measures. Age was negatively associated with
      three alcohol consumption measures. While students' importance of good grades was
      negatively associated with three alcohol consumption measures, academic
      performance in comparison with peers was negatively associated with heavy
      episodic drinking. Actual module mark was not associated with any alcohol
      consumption measure. CONCLUSIONS: Alcohol consumption showed negative
      associations with motivation for and subjectively achieved academic performance.
      University alcohol prevention activities might have positive impact on students'
      academic success.

PMID- 24319559
TI  - Assessment of health-promoting behavior and lifestyle of adolescents of a north
      Indian city.
AB  - BACKGROUND: Several health-compromising behaviors (e.g., smoking, alcohol) as
      well as health-enhancing behaviors (e.g., physical exercise, nutrition) are
      adopted in adolescence and they often persist into adulthood. Thus, there is a
      definite need to investigate the health behavior of adolescents rather than focus
      on adults since it will be far more difficult for adults to change their
      unhealthy habits adopted in their youth. Therefore, the present study was
      conducted to ascertain health-promoting behavior and lifestyle of university
      graduates of Chandigarh. METHODS: The present cross-sectional pilot study was
      conducted in Chandigarh during 2009 among university graduates of Chandigarh aged
      17-20 years. A semi-structured, pretested questionnaire comprising of 28 items
      was used to get information from students regarding their involvement in diet,
      physical exercise, spirituality and philanthropy. Height, weight, waist and hip
      circumference of the respondents were measured using standardized equipments and
      procedures. RESULTS: Mean score of health-promoting lifestyle profile of
      university graduates was found to be 67.5 +/- 12.1 (maximum attainable score =
      106). Fourteen students were found to be overweight. Frequent intake of fast food
      and less consumption of fruits and vegetables was reported by the students.
      Majority of students exercised as part of their daily routine. CONCLUSIONS: The
      result of the study showed that North Indian students had reasonably good
      orientations toward health behaviors, with a mean score of 67.5. The topics
      related to diet, physical exercise, spiritual growth and philanthropy promotion
      should be incorporated within the curriculum of students for their all round
      personality development.

PMID- 24319560
TI  - Schools' Cafeteria Status: Does it Affect Snack Patterns? A Qualitative Study.
AB  - BACKGROUND: The aim of this study was to evaluate patterns of students' snacks
      habits regarding to their schools' cafeteria status in Tehran by focus group
      discussion (FGD) technique. METHODS: Participants were 240 students (12-15 years
      old), selected from12 middle-schools in Tehran. The field study consisted of 24
      FGDs sessions; involving 8-10 participants. Collected data were coded,
      categorized and analyzed using constant comparative method. RESULTS: Over half of
      the students believed that snack consumption is necessary. Although, majority of
      students believed that their schools' cafeterias are not acceptable, they noted
      them as one of the necessary parts of school. Nearly half of the children were
      complaining of unvaried and expensive food items. The most purchased items were:
      Cookies, sandwiches with mayonnaise and ketchup, soft drinks and chocolate milk.
      Most of the students were interested in having roles in their cafeterias.
      CONCLUSIONS: Schools' cafeteria are significant sources of supplying adolescents'
      snacks, so developing hygienic stores containing healthy and nutritious food
      items is a key element to affect their snack selection positively. Reaching this
      goal requires a multi disciplinary approach through participation of students,
      school staff, parents, and the support of community and media.

PMID- 24319561
TI  - Educational needs assessment for psychiatry residents to prevent suicide: a
      qualitative approach.
AB  - BACKGROUND: Suicide is a commonly encountered and stressful event in professional
      life of any psychiatrist. Suicide risk assessment is a major gateway to patient
      treatment and management. It is a core competency requirement in training of
      psychiatry. The present study designed to assesseducational needsfor suicide
      prevention in residents of psychiatry in two medical schools in Iran, Isfahan
      University of Medical Sciences (IUMS) and Shahid Beheshti Medical University
      (SBUMS) inTehran. METHODS: This was a qualitative triangulation study, conducted
      in two steps. The first step was based on a phenomenological approach and the
      second was based on focus groups. The studied population was the psychiatric
      residents of IUMS and SBUMS. Purposive sampling was implemented until saturation.
      Interviews were performed. Colaizzi method was used to analyze the data. In the
      second step, participants attended a session, in which all final codes of the
      first step were discussed, and regarding the views, educational priorities and
      needs were listed. RESULTS: A total of 2047 codes, extracted from 31 interviews,
      analyzed through Colaizzi method, were categorized in three groups: Educational,
      facilities and processes, human resources. CONCLUSIONS: According to defects of
      current educational program, we suggest regular reevaluations and revisions of
      clinical training programs according to current needs.

PMID- 24319562
TI  - Symmetric Peripheral Gangrene Associated with H1N1 Infection.
AB  - More and more cases of H1N1 influenza are being detected in India and so also the
      variety of complications this virus can cause. Here, we report a case of
      symmetric peripheral gangrene following H1N1 infection. 

PMID- 24319563
TI  - Prevention of more complications in patients with head trauma.
AB  - Head trauma and brain injuries are common causes of emergency admission and
      usually predispose multiple psychiatric complications. In turn, the traumas often
      occur after some psychiatric disorders. Therefore, the complicated interaction of
      these factors often causes difficulties in diagnosis and management of the
      patients. The side-effects of surgical and medical treatments may also complicate
      these processes more, as well. In this study, we present a case of a young
      patient with these complex factors and discuss the diagnosis and management. 

PMID- 24319564
TI  - Iron and Folic Acid Consumption by the Ante-natal Mothers in a Rural Area of
      India in 2010.
AB  - BACKGROUND: The average rural Indian women enter her reproductive life,
      particularly in pregnancy, suffer from nutritional anemia due to iron deficiency.
      National program of India had implemented a strategy for supplementation of iron
      folic acid by means of iron folic acid (IFA) tablets at least 3 months during
      antenatal period. The study had been conducted to assess the proportion of
      pregnant mothers consumes the IFA tablets and the factors determine compliance.
      METHODS: A cross-sectional, community-based study was conducted in rural area of
      India on 50 antenatal mothers by multistage sampling technique. The data were
      analyzed by using SPSS 16 (Statistical Package for the Social Sciences, ver. 16),
      Chicago, considering the level of significance at 95%. RESULTS: The IFA tablet
      was adequately consumed by 62% mother among the study population. The consumption
      is more among the mother who were explained properly than those who were not
      explained by the health worker (chi(2)= 4.529, P < 0.05). CONCLUSIONS: The
      compliance of iron folic acid tablets was still far behind to reach the National
      Goal though the service component are quite strong by the front line workers and
      health providers. An effort should be given at the level of front line health
      workers by training and re-training them to improve the compliance of IFA
      consumption.

PMID- 24319565
TI  - Demographical and psychological determinants of depression, among a sample of
      Iranian male adolescents.
AB  - BACKGROUND: The prevalence of depression especially among youths is increasingly
      high. The present study is aimed to identify some demographic and psychological
      factors such as self-efficacy and perceived stress that may be related to
      depression among male adolescents. METHODS: Overall, 402 adolescent were selected
      for participation in the study using multistage sampling method. The participants
      completed a questionnaire including demographic, depression, self-efficacy, and
      perceived stress data. A multiple regression analysis and the Pearson correlation
      test were used for data analysis. SPSS version 17 software was used for
      performing analyses. RESULTS: The mean age of the adolescents was 15.44 (SD =
      0.68) years. The total mean score of depression was 16.02 +/- 9.14 and 153
      (38.1%) of participants showed depressive symptoms. Results showed that high
      levels of depression were associated with low level of self-efficacy and high
      level of perceived stress; also some demographic variables such as fathers' job
      and academic situation can be related to depression among male adolescents.
      CONCLUSIONS: Self-efficacy and perceived stress can be related to depression but
      the role of stress and self-efficacy in the etiology and forming of depression in
      adolescent are discussed. Therefore, more studies for approval of these
      associations should be considered.

PMID- 24319566
TI  - Health-care of Elderly: Determinants, Needs and Services.

PMID- 24319567
TI  - Comment on: Protective Role of Recombinant Human Erythropoietin in Kidney and
      Lung Injury Following Renal Bilateral Ischemia-reperfusion in Rat Model.

PMID- 24319568
TI  - LQTS-associated mutation A257G in alpha1-syntrophin interacts with the intragenic
      variant P74L to modify its biophysical phenotype.
AB  - The SNTA1-encoded alpha1-syntrophin (SNTA1) missense mutation, p.A257G, causes
      long QT syndrome (LQTS) by pathogenic accentuation of Nav1.5's sodium current
      (INa). Subsequently, we found p.A257G in combination with the SNTA1 polymorphism,
      p.P74L in 4 victims of sudden infant death syndrome (SIDS) as well as in 3 adult
      controls. We hypothesized that p.P74L-SNTA1 could functionally modify the
      pathogenic phenotype of p.A257G-SNTA1, thus explaining its occurrence in non-LQTS
      populations. The SNTA1 variants p.P74L, p.A257G, and the combination variant
      p.P74L/p.A257G were engineered using PCR-based overlap-extension and were co
      expressed heterologously with SCN5A in HEK293 cells. INa was recorded using the
      whole-cell method. Compared to wild-type (WT), the significant increase in peak
      INa and window current found with p.A257G was reversed by the intragenic variant
      p.P74L (p.P74L/p.A257G). These results report for the first time the intragenic
      rescue of an LQT-associated SNTA1 mutation when found in combination with the
      SNTA1 polymorphism p.P74L, suggesting an ever-increasing picture of complexity in
      terms of genetic risk stratification for arrhythmia.

PMID- 24319569
TI  - Improved neonatal survival through economically sustainable reorganization of a
      neonatal care unit in a developing country: 7-year experience in the Centre
      Medical Saint Camille (CMSC) of Ouagadougou, Burkina Faso.

PMID- 24319570
TI  - Diffuse large B-cell lymphoma in adults aged 75 years and older: a single
      institution analysis of cause-specific survival and prognostic factors.
AB  - BACKGROUND: Very elderly patients (75 years and older) with diffuse large B-cell
      lymphoma (DLBCL) will be increasingly considered for cancer treatment as the
      population ages, but are underrepresented in clinical trials. Here we report
      outcomes of very elderly DLBCL patients treated in the modern era at the Oregon
      Health and Science University (OHSU). METHODS: We queried the OHSU Tumor Registry
      for DLBCL cases treated since 2002. A total of 73 patients aged 75 years or older
      were analyzed under Institutional Review Board approval. RESULTS: With a median
      follow up of 31 months, cause-specific survival was 58% and overall survival 51%
      at 3 years. Incorporation of an anthracycline did not influence outcomes. More
      than one extranodal site or poor-risk disease by Revised International Prognostic
      Index score were adversely prognostic, but pathologic features studied were not.
      CONCLUSIONS: Very elderly patients with DLBCL require prospective studies, which
      employ novel risk stratification and therapeutic approaches.

PMID- 24319571
TI  - From clinical trials to clinical practice: single-agent carfilzomib adverse
      events and their management in patients with relapsed and/or refractory multiple
      myeloma.
AB  - Multiple myeloma is characterized by periods of remission followed by relapse,
      and eventually the disease becomes refractory to treatment. While patients with
      multiple myeloma frequently receive multiple lines of treatment, antimyeloma
      agents are associated with a number of toxicities that can impact their use and
      influence future treatment options. Patients with relapsed and/or refractory
      multiple myeloma are particularly challenging to treat due to the advanced state
      of their disease, typically greater resistance to treatment, and the presence of
      disease- and treatment-related comorbidities. An understanding of the safety
      profile of the therapeutic agents used in treating multiple myeloma is thus
      crucial for appropriate patient management. Single-agent carfilzomib has been
      approved in the United States for the treatment of patients with relapsed and
      refractory multiple myeloma, and has been shown to be efficacious and well
      tolerated in this setting. This review examines the frequency of common and
      significant hematologic and nonhematologic adverse events following
      administration of single-agent carfilzomib in four phase II trials in relapsed
      and/or refractory multiple myeloma, and provides practical recommendations for
      their management. 

PMID- 24319575
TI  - In vitro neuraotropic growth of cholangiocarcinoma: an experimental study.
AB  - OBJECTIVE: Perineural invasion of cholangiocarcinoma happens in the early stage
      of the disease but is often not recognized until its later stages. Research about
      the behaviour and mechanism of perineural invasion by cholangiocarcinoma is
      urgently needed for a useful new model. The aim of this work is to establish a
      novel model to address the problem. DESIGN: Neural cells and cholangiocarcinoma
      cells were co-cultured to mimic the neurotropic invasion of cholangiocarcinoma.
      SETTING: Human embryonic stem cells were induced to form neural cells by glial
      cell-derived neurotropic factor and retinoic acid; neural cells and
      cholangiocarcinoma cells were co-cultured in Transwell chamber. PARTICIPANTS:
      Human embryonic stem cells and cholangiocarcinoma cells were applied. MAIN
      OUTCOME MEASURES: Paired t-test was used to compare the counts of penetrating
      cholangiocarcinoma cells in co-culture and control group. RESULTS: Formation of
      neurospheres and neural-like cells were observed following induction at 24 and 48
      h, respectively; synapses were viewed to protrude from neural-like cell bodies
      after incubation for 96 h. Forty-eight hours after incubation, immunocytochemical
      staining of the cells showed that synaptophysin and glial fibrillary acidic
      protein were expressed in the neuron-like cells and gliocytes-like cells,
      respectively. The cholangiocarcinoma cells that had penetrated through the
      Matrigel/polyethylene terephthalate membrane from the upper chamber to the lower
      chamber of the Transwell in the co-culture group were significantly more numerous
      than those in the control group (68 +/- 8.3/field versus 46 +/- 5.7/field, P <
      0.05). CONCLUSION: The novel model is a valuable tool to study the perineural
      invasion of cholangiocarcinoma.

PMID- 24319572
TI  - Treatment and management of graft-versus-host disease: improving response and
      survival.
AB  - Graft-versus-host disease (GVHD) is a significant cause of morbidity and
      mortality following allogenic haematopoietic stem-cell transplantation and thus
      the focus of much ongoing research. Despite considerable advances in our
      understanding of the pathophysiology, diagnosis and predisposing factors for both
      acute and chronic forms of the disease, a standardised therapeutic strategy is
      still lacking. There is good evidence for initial treatment of both acute and
      chronic forms of the disease with corticosteroid therapy. However, the most
      effective approach to steroid-refractory disease remains controversial, with
      current practice based mainly on smaller studies and varying considerably between
      local institutions. Timely diagnosis, multidisciplinary working and good
      supportive care, including infection prophylaxis, are clearly important in
      optimizing response and survival in such patients. It is hoped that in the future
      systematic research strategies and the identification of novel therapeutic
      targets may improve outcome further. The following review aims to outline some of
      the existing options for the treatment and management of acute and chronic GVHD. 

PMID- 24319576
TI  - Right lower lobectomy following inhalation of a toy traffic cone.

PMID- 24319577
TI  - Histological evaluation of retrieved Copeland re-surfacing shoulder
      arthroplasties.

PMID- 24319578
TI  - Distribution of breast cancer subtypes among Jordanian women and correlation with
      histopathological grade: molecular subclassification study.
AB  - OBJECTIVE: To evaluate the hormone receptor status and human epidermal growth
      factor receptor 2 (HER2)/neu gene expression among Jordanian women with breast
      cancer. To classify our patients into molecular subtypes and to correlate the
      results with age of the patients and tumour grade. DESIGN: Evaluation of estrogen
      receptor (ER), PR and HER2/neu was done by standard immunohistochemical technique
      and subclassification into molecular subtypes. SETTING: Jordan University
      Hospital, Amman, Jordan. PARTICIPANTS: One hundred and ninety-three cases of
      breast cancer diagnosed at Jordan University Hospital. MAIN OUTCOME MEASURES:
      Molecular subtypes of breast cancer, age and tumour grade. RESULTS: ALL THE CASES
      WERE DIVIDED INTO TWO GROUPS: the young age group less or equal 50 years of age
      and the older age group more than 50 years of age. The cases were subclassified
      into luminal A, luminal B, basal cell like (BCL) and Her2/neu+. In older age
      group, the most common subtype was luminal A (72%). In this age group, most of
      the cases (48%) were of grade II. In younger age group, 47% of the cases were of
      luminal A subclass. In this age group, 42% were of grade I. CONCLUSIONS:
      Molecular subtyping of breast cancer is an essential predicting factor of tumour
      response to hormonal therapy. This fact puts increased stress on the urgent need
      for the development of reliable and reproducible classification systems.

PMID- 24319579
TI  - The challenges of obtaining ethics approval for a randomized, double-blind,
      placebo-controlled research study in Jersey.
AB  - BACKGROUND AND OBJECTIVE: A PhD project involving designing and implementing a
      small-scale clinical trial at Jersey General Hospital encountered a variety of
      difficulties in obtaining ethics approval due to Jersey's unique legal and
      constitutional position. Clarification of the necessary route of application took
      some 28 months. It was established that only local ethics approval is required
      for clinical trials taking place in the Channel Islands and that there is no need
      for Medicines and Healthcare products Regulatory Agency (MHRA) approval in the
      form of Clinical Trials Authorization (CTA), because Jersey falls outside the
      existing legal and regulatory framework. The experiences and findings gained from
      this project would prove of use to other researchers planning to conduct clinical
      trials in the Channel Islands.

PMID- 24319580
TI  - Relative age effect on Nobel laureates in the UK.

PMID- 24319581
TI  - How distressing is it to participate in medical research? A calibration study
      using an everyday events questionnaire.
AB  - OBJECTIVES: To investigate how distressing participating in medical research is
      perceived to be, compared to everyday events. DESIGN: Anonymous questionnaire.
      SETTING: Scotland and New Zealand. PARTICIPANTS: One hundred members of the
      Scottish general public, 94 University of Auckland students, 22 New Zealand
      Ministry of Health ethics committee members. MAIN OUTCOME MEASURES: Distress
      ratings made on a 0-10 scale for everyday events and common medical research
      procedures. RESULTS: Both general population and student samples generally rated
      the distress caused by participating in various medical research procedures as
      low or very low. Most research procedures were rated less than the distress
      caused by not being able to find a car park at a supermarket. In contrast, the
      ethics committee members rated the distress caused by most of the medical
      research procedures at a significantly higher level than the ratings of the
      student and general population samples. Ethics committee members overestimated
      the distress caused by interview or questionnaire assessments (M = 203.31%, SE =
      11.42, 95% CI [179.79, 226.83]) more than medical testing for research (M =
      158.06%, SE = 12.33, 95% CI [132.66, 183.46], p = 0.04) and everyday events (M =
      133.10%, SE = 7.80, 95% CI [117.03, 149.16], p < 0.001). CONCLUSIONS: Common
      medical research procedures are not rated as particularly distressing by the
      general public, and ethics committees may be adopting an over-protective role
      when evaluating research applications that involve the use of questionnaire or
      survey methodology.

PMID- 24319582
TI  - Electromagnetic hypersensitivity (EHS) in the media - a qualitative content
      analysis of Norwegian newspapers.
AB  - OBJECTIVES: Electromagnetic hypersensitivity (EHS) is a condition characterized
      by experiencing symptoms after perceived exposure to weak electromagnetic fields
      (EMFs). There is substantial debate concerning the aetiology of EHS, but
      experimental data indicate no association between EHS and actual presence of
      EMFs. Newspapers play a key role in shaping peoples' understanding of health
      related issues. The aim of this study was to describe the content of newspaper
      articles concerning aetiology and treatment of EHS. DESIGN: Qualitative content
      analysis of newspaper articles. SETTING: Norwegian newspaper articles were
      identified using a comprehensive electronic media archive. PARTICIPANTS:
      Norwegian newspaper articles published between 1 February 2006 and 11 August
      2010. MAIN OUTCOME MEASURES: Statements coded according to source of information,
      whether it was pro or con scientific evidence on EHS aetiology, and type of
      intervention presented as treatment option for EHS. RESULTS: Of the statements
      concerning EHS aetiology (n = 196), 35% (n = 69) were categorized as pro
      evidence, 65% (n = 127) as con evidence. Of the statements about EHS
      interventions assessed, 78% (n = 99) were categorized as 'radiance reduction', 4%
      (n = 5) as 'complementary medicine', and 18% (n = 23) as 'other'. Cognitive
      behavioural therapy (CBT) and psychotropic drugs were never presented as possible
      treatment options for EHS. CONCLUSIONS: The newspaper media discourse of EHS
      aetiology and recommended treatment interventions is much in conflict with the
      current evidence in the field. The majority of statements concerning aetiology
      convey that EHS is related to the presence of weak EMFs, and radiance reduction
      as the most frequently conveyed measure to reduce EHS-related symptoms.

PMID- 24319583
TI  - Increasing patients' ability to identify their physicians with a photo album: a
      prospective study.
AB  - OBJECTIVES: Patients in teaching hospitals often encounter difficulty in
      correctly identifying their physicians. We hypothesized that a photo album of
      physicians might increase the ability of patients to correctly identify their
      physicians and hence conducted this study to test the hypothesis. DESIGN: A
      prospective study was conducted. SETTING: Department of Surgery, The Third
      XiangYa Hospital. PARTICIPANTS: THE PATIENTS WERE DIVIDED INTO TWO GROUPS ON
      ADMISSION: group A as intervention group (n = 75) and group B as control group (n
      = 94). All the patients were verbally informed of their medical team but only the
      patients in group A (the intervention group) were also shown the photos of their
      medical team. MAIN OUTCOME MEASURES: One day before being discharged, the
      patients in group A (the intervention group) were asked to return the photo
      albums, and all the patients from both groups were asked to give the names of
      their caring physicians prior to departure from the hospital. RESULTS: Only 53%
      of the patients (50 out of 94) in group B (the control group) could give at least
      one of their physicians' name, while 85% of the patients (64 out of 75) in group
      A (the intervention group) could tell at least one of their physicians' name;
      there is a significant difference (p < 0.005, 95% CI, 17.4-44.7%). CONCLUSION:
      Patients' ability to identify their physicians can be significantly increased
      with a photo album.

PMID- 24319584
TI  - Beyond a prolonged QT interval.

PMID- 24319585
TI  - Hypertension, sweating and palpitation in a psychotic patient - don't miss the
      somatic cause.

PMID- 24319586
TI  - Atypical anaphylaxis using 'dual technique' during sentinel lymph node biopsy.

PMID- 24319587
TI  - Bilateral patellar tendon rupture.

PMID- 24319588
TI  - Retropharyngeal abscess in a six-week-old child: an approach to management.

PMID- 24319589
TI  - Acute myeloid leukemia: potential for new therapeutic approaches targeting mRNA
      translation pathways.
AB  - Despite advances in molecular research related to acute myeloid leukemia (AML)
      and a better understanding of the mechanisms of leukemogenesis and
      pathophysiology of the disease, the pharmacological agents used in the treatment
      of AML have remained essentially unchanged for the last three decades. Advances
      in the clinical management of AML patients have been achieved by defining better
      molecular prognostic markers, but there remains a need for new targeted drugs
      that disrupt non-overlapping pathways in leukemia cells. The mTOR cellular
      cascade is critical for cell metabolism, growth, proliferation and survival.
      Extensive preclinical work suggests that targeting mTOR may provide a powerful
      approach to block AML precursor cells, while other findings suggest enhanced
      antileukemic effects by combining mTOR inhibitors with traditional chemotherapy.
      Such combinations may increase antileukemic responses further, offering unique
      ways to overcome leukemic cell resistance and to eliminate primitive leukemic
      precursors.

PMID- 24319590
TI  - HEARING, PSYCHOPHYSICS, AND COCHLEAR IMPLANTATION: EXPERIENCES OF OLDER
      INDIVIDUALS WITH MILD SLOPING TO PROFOUND SENSORY HEARING LOSS.
AB  - In a previous paper we reported the frequency selectivity, temporal resolution,
      nonlinear cochlear processing, and speech recognition in quiet and in noise for 5
      listeners with normal hearing (mean age 24.2 years) and 17 older listeners (mean
      age 68.5 years) with bilateral, mild sloping to profound sensory hearing loss
      (Gifford et al., 2007). Since that report, 2 additional participants with hearing
      loss completed experimentation for a total of 19 listeners. Of the 19 with
      hearing loss, 16 ultimately received a cochlear implant. The purpose of the
      current study was to provide information on the pre-operative psychophysical
      characteristics of low-frequency hearing and speech recognition abilities, and on
      the resultant postoperative speech recognition and associated benefit from
      cochlear implantation. The current preoperative data for the 16 listeners
      receiving cochlear implants demonstrate: 1) reduced or absent nonlinear cochlear
      processing at 500 Hz, 2) impaired frequency selectivity at 500 Hz, 3) normal
      temporal resolution at low modulation rates for a 500-Hz carrier, 4) poor speech
      recognition in a modulated background, and 5) highly variable speech recognition
      (from 0 to over 60% correct) for monosyllables in the bilaterally aided
      condition. As reported previously, measures of auditory function were not
      significantly correlated with pre- or post-operative speech recognition - with
      the exception of nonlinear cochlear processing and preoperative sentence
      recognition in quiet (p=0.008) and at +10 dB SNR (p=0.007). These correlations,
      however, were driven by the data obtained from two listeners who had the highest
      degree of nonlinearity and preoperative sentence recognition. All estimates of
      postoperative speech recognition performance were significantly higher than
      preoperative estimates for both the ear that was implanted (p<0.001) as well as
      for the best-aided condition (p<0.001). It can be concluded that older
      individuals with mild sloping to profound sensory hearing loss have very little
      to no residual nonlinear cochlear function, resulting in impaired frequency
      selectivity as well as poor speech recognition in modulated noise. These same
      individuals exhibit highly significant improvement in speech recognition in both
      quiet and noise following cochlear implantation. For older individuals with mild
      to profound sensorineural hearing loss who have difficulty in speech recognition
      with appropriately fitted hearing aids, there is little to lose in terms of
      psychoacoustic processing in the low-frequency region and much to gain with
      respect to speech recognition and overall communication benefit. These data
      further support the need to consider factors beyond the audiogram in determining
      cochlear implant candidacy, as older individuals with relatively good low
      frequency hearing may exhibit vastly different speech perception abilities -
      illustrating the point that signal audibility is not a reliable predictor of
      performance on supra-threshold tasks such as speech recognition.

PMID- 24319591
TI  - Essential role of thioredoxin 2 in mitigating oxidative stress in retinal
      epithelial cells.
AB  - The retina is constantly subjected to oxidative stress, which is countered by
      potent antioxidative systems present in retinal pigment epithelial (RPE) cells.
      Disruption of these systems leads to the development of age-related macular
      degeneration. Thioredoxin 2 (Trx2) is a potent antioxidant, which acts directly
      on mitochondria. In the present study, oxidative stress was induced in the human
      RPE cell line (ARPE-19) using 4-hydroxynonenal (4-HNE) or C2-ceramide. The
      protective effect of Trx2 against oxidative stress was investigated by assessing
      cell viability, the kinetics of cell death, mitochondrial metabolic activity, and
      expression of heat shock proteins (Hsps) in Trx2-overexpressing cell lines
      generated by transfecting ARPE cells with an adeno-associated virus vector
      encoding Trx2. We show that overexpression of Trx2 reduced cell death induced by
      both agents when they were present in low concentrations. Moreover, early after
      the induction of oxidative stress Trx2 played a key role in the maintenance of
      the cell viability through upregulation of mitochondrial metabolic activity and
      inhibition of Hsp70 expression. 

PMID- 24319592
TI  - Acute effects of an energy drink on myocardial function assessed by conventional
      echo-Doppler analysis and by speckle tracking echocardiography on young healthy
      subjects.
AB  - Purpose. Previous studies have underlined the effects of the energy drinks
      containing caffeine end taurine on the cardiovascular system. The aim of this
      study was to determine acute changes on echocardiographic parameters assessed by
      conventional echo-Doppler analysis and by speckle tracking echocardiography after
      the consumption of an energy drink in a young healthy population. Methods.
      measurement of blood pressure, electrocardiographic, and echocardiographic
      examination were performed on 35 healthy subjects (mean age 25 +/- 2 years, 16
      men), at baseline and one hour after the consumption of a body surface area
      indexed amount of an energy drink (168 mL/m(2)) containing caffeine (0.03%) and
      taurine (0.4%). Results. The analysis of left ventricular function showed a
      significant increase of mean relative values of MAPSE (+11%; P < 0.001), global
      longitudinal strain (+10%, P = 0.004), and left ventricular twisting (+22%, P <
      0.0001) in respect to baseline. Also, right ventricular function parameters
      appeared significantly increased after energy drink consumption, as TAPSE (+15%,
      P < 0.0001), global, and free wall right ventricular longitudinal strain (+8%, P
      = 0.001; +5%, P = 0.1, resp.). Conclusion. In conclusion, the consumption of the
      ED in our population showed a significant increase of right and left ventricular
      myocardial function, suggesting a possible positive inotropic effect related to
      the substances contained therein. 

PMID- 24319593
TI  - Updates on morphea: role of vascular injury and advances in treatment.
AB  - Morphea and systemic sclerosis are fibrosing disorders of the skin that share
      common inflammatory and immunologic pathways that are responsible for the
      vascular changes, increased collagen production, and extracellular matrix
      proliferation seen in both conditions. Recent advances in molecular biology
      techniques have furthered our knowledge of the potential underlying pathogenic
      mechanisms and offer new and provocative areas of research for novel diagnostic
      and therapeutic interventions. This review focuses on the role of vascular injury
      in the development of morphea, the use of ultrasonography as a diagnostic
      modality, and well-established and newly proposed treatments. 

PMID- 24319594
TI  - Exergaming as a strategic tool in the fight against childhood obesity: a
      systematic review.
AB  - Improper use of electronic media is considered a major contributing factor to
      childhood obesity. However, exergames, a new generation of active games, have
      made it possible to combine electronic entertainment with physical exercise. The
      purpose of this systematic review was to analyze the use of exergaming as a
      strategic tool in the fight against childhood obesity. Information was retrieved
      from the databases SciELO, LILACS, Pubmed, Ebsco, and Science Direct, using the
      search words "egames," "exergames," "exergaming," "new generation of video
      games," "active video games," "energy expenditure," "body composition," and
      "physical activity" in English and Portuguese, covering the period January 2008
      to April 2012. Nine articles met the inclusion criteria. Exergaming was found to
      increase physical activity levels, energy expenditure, maximal oxygen uptake,
      heart rate, and percentage of physical activity engaged in and to reduce waist
      circumference and sedentary screen time. Thus, exergaming may be considered a
      highly relevant strategic tool for the adoption of an active and healthy
      lifestyle and may be useful in the fight against childhood obesity. 

PMID- 24319595
TI  - Newspaper coverage effects on the promotion of a lifestyle intervention program.
AB  - The study's purpose was to measure the impact of an individually designed
      lifestyle intervention program on the readers of a regional newspaper. A
      newspaper with 180,000 daily readers covered a story about three untrained and
      overweight adults who participated in an individually designed lifestyle
      intervention program. Their goals were to become physically fit and run a half
      marathon (21.1 km) after 14 weeks of training. The newspaper published on average
      three weekly articles throughout the project period, including the weekly
      training program and a record of the physical improvements made by the
      participants. The number of hits on the project's web site was recorded. Spin-off
      effects on the responses of readers were mapped. The project's web site had
      25,000 unique weekly hits. Significant spin-off effects included the
      establishment of training groups which were still active after two years and the
      launch of a similar project by another regional newspaper. This individually
      designed lifestyle intervention program was successfully scaled up and reached a
      large number of the newspaper's readers. The collaboration between a newspaper
      and exercise researchers could also be adapted to other press media and
      represents a novel approach to improve participation in physical activities. 

PMID- 24319596
TI  - Efficacy of micromobile foot compression device in increasing lower limb venous
      blood flow.
AB  - Background. A novel, micromobile foot compression device (MMC) has been developed
      to reduce the risk of venous thromboembolism associated with prolonged seated
      immobility. Objective. To compare the efficacy of the MMC with graduated
      compression stockings in augmenting lower limb venous blood flow.
      Patients/Methods. Twenty participants were randomised to wear the MMC or a
      graduated compression stocking (GCS) on either the left or right leg while
      seated. Doppler ultrasound measurements of popliteal vein blood flow and leg
      circumference measurements were made -30 and -10 minutes (baseline) and +30 and
      +60 minutes following application of the interventions. The primary outcome
      variable was peak systolic velocity. A mixed linear model was used, with
      covariates including baseline measurement, randomised side, time, and a time by
      interaction term. Results. The mean popliteal vein peak systolic velocity at 60
      minutes with the MMC was 20.1 cm/s which was significantly higher than with the
      GCS (difference 14.1 cm/s 95% CI 12.1-16.2), representing a 3.8-fold increase
      from baseline. Conclusion. The MMC resulted in a marked increase in lower limb
      venous blood flow which suggests that it may have efficacy in reducing the risk
      of venous thromboembolism associated with prolonged seated immobility, such as
      long distance air travel. 

PMID- 24319597
TI  - Carotid atherosclerosis as a surrogate maker of cardiovascular disease in
      diabetic patients.
AB  - Many studies have shown that carotid intima-media thickness (IMT) is associated
      with cardiovascular disease (CVD). Although it remains inconclusive whether
      assessment of carotid IMT is useful as a screening test for CVD in Japanese
      diabetic patients, a total of 271 patients (151 men aged 66 +/- 10 (standard
      deviation) years and 220 women aged 71 +/- 8 years) were divided into two groups
      based on the presence of CVD. We cross-sectionally assessed the ability of
      carotid IMT to identify CVD corresponding to treatment that was examined by
      receiver-operating characteristic (ROC) curve analyses. Among the 271 diabetic
      patients, 199 non-CVD and 72 CVD patients were examined. Multiple linear
      regression analysis using the presence of CVD as an objective variable showed
      that carotid IMT (beta = 0.259, P < 0.001) as well as other confounding factors
      was a significant independent contributing factor. The ROC curve analysis showed
      that the best marker of CVD was carotid IMT, with an area under the ROC curve of
      0.718 (95% confidence interval (CI), 0.650-0.785). The greatest sensitivity and
      specificity were obtained when the cut-off value of mean carotid IMT was set at
      0.95 mm (sensitivity = 0.71, specificity = 0.60, and accuracy = 0.627). Our study
      suggests that carotid IMT may be useful for screening diabetic patients with CVD.

PMID- 24319598
TI  - Low-level laser on hearing: is there an effect?

PMID- 24319599
TI  - Making memories: the development of long-term visual knowledge in children with
      visual agnosia.
AB  - There are few reports about the effects of perinatal acquired brain lesions on
      the development of visual perception. These studies demonstrate nonseverely
      impaired visual-spatial abilities and preserved visual memory. Longitudinal data
      analyzing the effects of compromised perceptions on long-term visual knowledge in
      agnosics are limited to lesions having occurred in adulthood. The study of
      children with focal lesions of the visual pathways provides a unique opportunity
      to assess the development of visual memory when perceptual input is degraded. We
      assessed visual recognition and visual memory in three children with lesions to
      the visual cortex having occurred in early infancy. We then explored the time
      course of visual memory impairment in two of them at 2  years and 3.7  years from
      the initial assessment. All children exhibited apperceptive visual agnosia and
      visual memory impairment. We observed a longitudinal improvement of visual memory
      modulated by the structural properties of objects. Our findings indicate that
      processing of degraded perceptions from birth results in impoverished memories.
      The dynamic interaction between perception and memory during development might
      modulate the long-term construction of visual representations, resulting in less
      severe impairment.

PMID- 24319601
TI  - Soft tissue management and prosthetic rehabilitation in a tongue cancer patient.
AB  - One major challenge in treating head and neck oncologic patients is to achieve an
      acceptable recovery of physiologic functions compatible with the complete tumor
      excision. However, after tumor resection, some patients present a surgically
      altered anatomy incompatible with prosthetic rehabilitation, unless some soft
      tissue correction is carried out. The aim of the present study is to describe the
      overall mandibular prosthetic rehabilitation of a postoncologic patient focusing
      on the possibility of soft tissue correction as a part of the treatment. A 72
      year-old woman, who undergone a hemiglossectomy for squamous cell carcinoma
      several years before, was referred to our department needing a new prosthesis.
      The patient presented partial mandibular edentulism, defects in tongue mobility,
      and a bridge of scar tissue connecting one side of the tongue to the alveolar
      ridge. A diode laser (980 nm) was used to remove the fibrous scar tissue. After
      reestablishing a proper vestibular depth and soft tissue morphology, two implants
      were placed in the interforaminal region of the mandible to support an
      overdenture. 

PMID- 24319602
TI  - Aesthetic rehabilitation of oligodontia in primary dentition with adhesive
      partial denture.
AB  - The primary teeth are essential for bone development and establishment of the
      arches on occlusion. Thus, the congenitally absence of teeth may trigger a shift
      in the balance of the occlusion, promoting disharmony in the structures of the
      maxilla-mandibular system. However, some interventions are possible to be
      performed in these cases even in pediatric patients, to redirect growth,
      preventing growth deviations and reestablishing the aesthetic. The aim of this
      paper is to report the treatment of a 4-year-old child presenting congenitally
      absence of mandibular central and lateral incisors and maxilla lateral incisors,
      which consequently compromises aesthetics, occlusal function, and the development
      and the functional growth of the bones. The oral rehabilitation was performed
      with an adhesive partial denture, which was able to restore the aesthetic and the
      occlusal function, therefore being a viable alternative in the treatment of this
      patient of little age. 

PMID- 24319603
TI  - Nonsyndromic familial oligodontia with multiple dens invaginatus: a case report
      of an unusual case.
AB  - Oligodontia is a rare dental anomaly with a prevalence of 0.3% in permanent teeth
      and much less frequency in the primary dentition. Familial oligodontia represents
      an absence of varying numbers of primary and/or secondary teeth as an isolated
      trait. It is a complex and multifactorial condition. Many explanations
      evolutionary, genetic, and environmental-have been proposed as the etiology.
      Simultaneous with oligodontia are often the different positional changes of the
      existing teeth, their morphology, size, and growth disturbances of the
      maxillofacial skeleton. Early recognition is vital to provide adequate treatment
      and prevent squeal. Multidisciplinary referral or consultation is thus important
      in treatment planning to improve function and esthetics. The present paper
      reports a rare case of familial oligodontia associated with multiple dense
      invaginatus and microdontia. 

PMID- 24319600
TI  - Translational approach to behavioral learning: lessons from cerebellar
      plasticity.
AB  - The role of cerebellar plasticity has been increasingly recognized in learning.
      The privileged relationship between the cerebellum and the inferior olive offers
      an ideal circuit for attempting to integrate the numerous evidences of neuronal
      plasticity into a translational perspective. The high learning capacity of the
      Purkinje cells specifically controlled by the climbing fiber represents a major
      element within the feed-forward and feedback loops of the cerebellar cortex.
      Reciprocally connected with the basal ganglia and multimodal cerebral domains,
      this cerebellar network may realize fundamental functions in a wide range of
      behaviors. This review will outline the current understanding of three main
      experimental paradigms largely used for revealing cerebellar functions in
      behavioral learning: (1) the vestibuloocular reflex and smooth pursuit control,
      (2) the eyeblink conditioning, and (3) the sensory envelope plasticity. For each
      of these experimental conditions, we have critically revisited the chain of
      causalities linking together neural circuits, neural signals, and plasticity
      mechanisms, giving preference to behaving or alert animal physiology. Namely,
      recent experimental approaches mixing neural units and local field potentials
      recordings have demonstrated a spike timing dependent plasticity by which the
      cerebellum remains at a strategic crossroad for deciphering fundamental and
      translational mechanisms from cellular to network levels. 

PMID- 24319604
TI  - Application of a Stability-Indicating HPTLC Method for Simultaneous Quantitative
      Determination of Olmesartan Medoxomil and Hydrochlorothiazide in Pharmaceutical
      Dosage Forms.
AB  - A rapid, precise, sensitive, economical, and validated high performance thin
      layer chromatographic method is developed for simultaneous quantification of
      olmesartan medoxomil and hydrochlorothiazide in combined tablet dosage form. The
      method used amlodipine as internal standard (IS). Chromatographic separations
      were achieved on silica gel 60 F254 plates using toluene-methanol-ethyl acetate
      acetone (2.5 : 1 : 0.5 : 2, v/v/v/v) as mobile phase. Densitometric analysis was
      carried out in the reflectance mode at 258 nm. Calibration curves were linear
      over a range of 80-480 ng/band for olmesartan medoxomil and 25-150 ng/band for
      hydrochlorothiazide. The detection and quantification limits were found to be
      18.12 and 56.35 ng/band for olmesartan medoxomil and 6.31 and 18.56 ng/band for
      hydrochlorothiazide, respectively. Intra- and interassay precision provided
      relative standard deviations lower than 2% for both analytes. Recovery from 99.60
      to 101.22% for olmesartan medoxomil and 98.30 to 99.32% for hydrochlorothiazide
      show good accuracy. Both the drugs were also subjected to acid, alkali,
      oxidation, heat, and photodegradation studies. The degradation products obtained
      were well resolved from pure drugs with significantly different R f values. As
      the method could effectively separate the drugs from their degradation products,
      it can be used for stability-indicating analysis. Validation of the method was
      carried out as per international conference on harmonization (ICH) guidelines. 

PMID- 24319605
TI  - Implementing the international health regulations (2005) in the World Health
      Organization Western Pacific Region.

PMID- 24319606
TI  - The legacies of SARS - international preparedness and readiness to respond to
      future threats in the Western Pacific Region.

PMID- 24319607
TI  - Human resources for health: lessons from the cholera outbreak in Papua New
      Guinea.
AB  - ISSUE: Papua New Guinea is striving to achieve the minimum core requirements
      under the International Health Regulations in surveillance and outbreak response,
      and has experienced challenges in the availability and distribution of health
      professionals. CONTEXT: Since mid-2009, a large cholera outbreak spread across
      lowland regions of the country and has been associated with more than 15 500
      notifications at a case fatality ratio of 3.2%. The outbreak placed significant
      pressure on clinical and public health services. ACTION: We describe some of the
      challenges to cholera preparedness and response in this human resource-limited
      setting, the strategies used to ensure effective cholera management and lessons
      learnt. OUTCOME: Cholera task forces were useful to establish a clear system of
      leadership and accountability for cholera outbreak response and ensure
      efficiencies in each technical area. Cholera outbreak preparedness and response
      was strongest when human resource and health systems functioned well before the
      outbreak. Communication relied on coordination of existing networks and methods
      for empowering local leaders and villagers to modify behaviours of the
      population. DISCUSSION: In line with the national health emergencies plan, the
      successes of human resource strategies during the cholera outbreak should be
      built upon through emergency exercises, especially in non-affected provinces.
      Population needs for all public health professionals involved in health emergency
      preparedness and response should be mapped, and planning should be implemented to
      increase the numbers in relevant areas. Human resource planning should be
      integrated with health emergency planning. It is essential to maintain and
      strengthen the human resource capacities and experiences gained during the
      cholera outbreak to ensure a more effective response to the next health
      emergency.

PMID- 24319608
TI  - The Pacific experience: supporting small island countries and territories to meet
      their 2012 International Health Regulations (2005) commitments.
AB  - ISSUE: By 15 June 2012, States Parties to the International Health Regulations
      (2005), or IHR (2005), were required to have established the core capacities
      required to implement Annex 1 of IHR (2005). CONTEXT: The Pacific is home to 10
      million people spread over 21 Pacific island countries and territories. Seven of
      those have populations of less than 25 000 people; 14 of the 21 Pacific island
      countries and territories are States Parties to the IHR (2005). ACTION: The World
      Health Organization Division of the South Pacific embarked on an initiative to
      support Pacific Island States Parties meet their 15 June 2012 IHR obligations. We
      adapted the 2012 IHR Monitoring Questionnaire (IHRMQ) to assist Pacific island
      countries and territories determine if they had met the capacities required to
      implement Annex 1 of the IHR (2005). If a Pacific island country or territory
      determined that it had not yet met the requirements, it could use the assessment
      outcome to develop a plan to address identified gaps. OUTCOME: Direct support was
      provided to 19 of 21 (91%) Pacific island countries and territories including 13
      of 14 (93%) States Parties. Twelve of 14 (86%) fulfilled their requirements by 15
      June 2012; those that had not yet met the requirements requested extensions and
      submitted plans describing how the IHR core capacities would be met. DISCUSSION:
      Adapting the 2012 IHRMQ for this purpose provided an efficient tool for assessing
      national capacity to implement Annex 1 of IHR (2005) and provided clear
      indication of what capacities required strengthening.

PMID- 24319609
TI  - Event-based surveillance in Papua New Guinea: strengthening an International
      Health Regulations (2005) core capacity.
AB  - Under the International Health Regulations (2005), Member States are required to
      develop capacity in event-based surveillance (EBS). The Papua New Guinea National
      Department of Health established an EBS system during the influenza pandemic in
      August 2009. We review its performance from August 2009 to November 2012, sharing
      lessons that may be useful to other low-resource public health practitioners
      working in surveillance. We examined the EBS system's event reporting, event
      verification and response. Characteristics examined included type of event,
      source of information, timeliness, nature of response and outcome. Sixty-one
      records were identified. The median delay between onset of the event and date of
      reporting was 10 days. The largest proportion of reports (39%) came from
      Provincial Health Offices, followed by direct reports from clinical staff (25%)
      and reports in the media (11%). Most (84%) of the events were substantiated to be
      true public health events, and 56% were investigated by the Provincial Health
      Office alone. A confirmed or probable etiology could not be determined in 69% of
      true events. EBS is a simple strategy that forms a cornerstone of public health
      surveillance and response particularly in low-resource settings such as Papua New
      Guinea. There is a need to reinforce reporting pathways, improve timeliness of
      reporting, expand sources of information, improve feedback and improve diagnostic
      support capacity. For it to be successful, EBS should be closely tied to
      response. 

PMID- 24319610
TI  - International Health Regulations (2005): public health event communications in
      the Western Pacific Region.

PMID- 24319611
TI  - Ongoing outbreak of dengue serotype-3 in Solomon Islands, January to May 2013.
AB  - INTRODUCTION: In January 2013, clinicians in Honiara, Solomon Islands noted
      several patients presenting with dengue-like illness. Serum from three cases
      tested positive for dengue by rapid diagnostic test. Subsequent increases in
      cases were reported, and the outbreak was confirmed as being dengue serotype-3 by
      further laboratory tests. This report describes the ongoing outbreak
      investigation, findings and response. METHODS: Enhanced dengue surveillance was
      implemented in the capital, Honiara, and in the provinces. This included training
      health staff on dengue case definitions, data collection and reporting. Vector
      surveillance was also conducted. RESULTS: From 3 January to 15 May 2013, 5254
      cases of suspected dengue were reported (101.8 per 10 000 population), including
      401 hospitalizations and six deaths. The median age of cases was 20 years (range
      zero to 90), and 86% were reported from Honiara. Both Aedes aegyti and Aedes
      albopictus were identified in Honiara. Outbreak response measures included
      clinical training seminars, vector control activities, implementation of
      diagnostic and case management protocols and a public communication campaign.
      DISCUSSION: This was the first large dengue outbreak documented in Solomon
      Islands. Factors that may have contributed to this outbreak include a largely
      susceptible population, the presence of a highly efficient dengue vector in
      Honiara, a high-density human population with numerous breeding sites and
      favourable weather conditions for mosquito proliferation. Although the number of
      cases has plateaued since 1 April, continued enhanced nationwide surveillance and
      response activities are necessary.

PMID- 24319612
TI  - A family cluster of nitrite poisoning, Suzhou City, Jiangsu Province, China,
      2013.
AB  - BACKGROUND: In April 2013, a hospital in Suzhou City notified authorities of a
      patient with nitrite poisoning with two other family members who had similar
      toxic symptoms five days prior. We investigated the event to identify the cause,
      source and possible route of contamination. METHODS: A case was defined as any
      person living in the Yang Shan Hua Yuan community who had been diagnosed with
      cyanoderma and food poisoning symptoms from 15 to 25 April 2013. Active case
      finding was conducted by interviewing community residents and reviewing medical
      records from local clinics; information was then retrospectively collected on the
      patient's food history, cooking procedures and food sources. RESULTS: We
      identified three nitrite poisoning cases, one male and two females, from the same
      family. The time between dinner and onset of illness was less than an a hour. A
      retrospective survey showed that a substance presumed to be sugar mixed with
      asparagus on 17 April and with stir-fried asparagus on 21 April was the suspected
      contaminant. The presumed sugar came from a clean-up of a neighbouring rental
      house. Nitrite was detected in a vomitus sample, the sugar substance and two
      leftover food samples. CONCLUSION: This family cluster of nitrite poisoning
      resulted from the mistaken use of nitrite as sugar to cook dishes. We recommend
      that sodium nitrite be dyed a bright colour to prevent such a mistake and that
      health departments strengthen food hygiene education to alert people about the
      danger of eating unidentified food from an unknown source.

PMID- 24319613
TI  - Ongoing rubella outbreak among adults in Tokyo, Japan, June 2012 to April 2013.
AB  - INTRODUCTION: A large rubella outbreak has been occurring in Tokyo, Japan since
      June 2012. Rubella vaccination, introduced in Japan in 1976, has targeted
      different age groups, resulting in a large proportion of the current population
      being unvaccinated. METHODS: Rubella cases reported in Tokyo from 2 January 2012
      to 21 April 2013 were analysed. A clinical case had generalized maculopapular
      rash, fever and lymphadenopathy; a laboratory-confirmed case was a clinical case
      with a positive serology or polymerase chain reaction test for rubella. A
      descriptive analysis of cases by age, sex, vaccination history and other
      epidemiological information was conducted. RESULTS: A total of 2382 cases were
      reported from all areas of Tokyo. Three-quarters were male (n = 1823; 76.5%); the
      highest number of cases occurred among males aged 35-39 years and females aged 20
      24 years. About a third of males (27%) and females (32%) reported never receiving
      rubella vaccination, with 68% and 56%, respectively, having an unknown
      vaccination status. DISCUSSION: This outbreak reflects the changing, yet
      incomplete, immunization policies for rubella in Japan that may increase the risk
      of congenital rubella syndrome (CRS). To suppress the outbreak of rubella and
      prevent CRS cases, we recommend vaccination for the entire susceptible
      population.

PMID- 24319614
TI  - Epidemiology of the 2012 influenza season in Victoria, Australia.
AB  - OBJECTIVE: To assess the magnitude and severity of the 2012 influenza season in
      Victoria, Australia using surveillance data from five sources. METHODS: Data from
      influenza notifications, sentinel general practices, a sentinel hospital network,
      a sentinel locum service and strain typing databases for 2012 were descriptively
      analysed. RESULTS: Influenza and influenza-like illness activity was moderate
      compared to previous years, although a considerable increase in notified
      laboratory-confirmed influenza was observed. Type A influenza comprised between
      83% and 87% of cases from the general practitioners, hospitals and notifiable
      surveillance data. Influenza A/H3 was dominant in July and August, and most
      tested isolates were antigenically similar to the A/Perth/16/2009 virus used in
      the vaccine. There was a smaller peak of influenza type B in September. No tested
      viruses were resistant to any neuraminidase inhibitor antivirals. Higher
      proportions of type A/H3, hospitalized cases and those with a comorbid condition
      indicated for influenza vaccination were aged 65 years or older. Influenza
      vaccination coverage among influenza-like illness patients was 24% in sentinel
      general practices and 50% in hospitals. DISCUSSION: The 2012 influenza season in
      Victoria was average compared to previous years, with an increased dominance of
      A/H3 accompanied by increases in older and hospitalized cases. Differences in
      magnitude and the epidemiological profile of cases detected by the different data
      sources demonstrate the importance of using a range of surveillance data to
      assess the relative severity of influenza seasons.

PMID- 24319616
TI  - Vibrio cholerae antimicrobial drug resistance, Papua New Guinea, 2009-2011.

PMID- 24319617
TI  - Management of simultaneous bilateral neck of femur fractures in an elderly
      patient.
AB  - Simultaneous bilateral neck of femur fracture is rare. There have been few
      reports of such a condition in the literature. This uncommon pattern of injury
      has been associated with high-energy trauma, underlying bone disease, and seizure
      disorders. We describe our experience of such a condition involving an elderly
      patient with significant cardiovascular comorbidity. The operative approach
      involved single-stage repair of both the involved joints. Bilateral uncemented
      hemi-arthroplasty was performed using a single tray of sterile surgical
      instruments and 2 sterile drapes. We report a satisfactory outcome. Uncemented
      arthroplasty should be considered in such a case so as to minimize the risk of a
      possible bone cement implantation syndrome. 

PMID- 24319615
TI  - Seasonal influenza vaccine policies, recommendations and use in the World Health
      Organization's Western Pacific Region.
AB  - OBJECTIVE: Vaccination is the most effective way to prevent seasonal influenza
      and its severe outcomes. The objective of our study was to synthesize information
      on seasonal influenza vaccination policies, recommendations and practices in
      place in 2011 for all countries and areas in the Western Pacific Region of the
      World Health Organization (WHO). METHODS: Data were collected via a questionnaire
      on seasonal influenza vaccination policies, recommendations and practices in
      place in 2011. RESULTS: Thirty-six of the 37 countries and areas (97%) responded
      to the survey. Eighteen (50%) reported having established seasonal influenza
      vaccination policies, an additional seven (19%) reported having recommendations
      for risk groups for seasonal influenza vaccination only and 11 (30%) reported
      having no policies or recommendations in place. Of the 25 countries and areas
      with policies or recommendations, health-care workers and the elderly were most
      frequently recommended for vaccination; 24 (96%) countries and areas recommended
      vaccinating these groups, followed by pregnant women (19 [76%]), people with
      chronic illness (18 [72%]) and children (15 [60%]). Twenty-six (72%) countries
      and areas reported having seasonal influenza vaccines available through public
      funding, private market purchase or both. Most of these countries and areas
      purchased only enough vaccine to cover 25% or less of their populations.
      DISCUSSION: In light of the new WHO position paper on influenza vaccines
      published in 2012 and the increasing availability of country-specific data,
      countries and areas should consider reviewing or developing their seasonal
      influenza vaccination policies to reduce morbidity and mortality associated with
      annual epidemics and as part of ongoing efforts for pandemic preparedness.

PMID- 24319618
TI  - Avascular necrosis of femoral head: a rare complication of a common fracture in
      an octogenarian.
AB  - Avascular necrosis (AVN) of the femoral head is a relatively uncommon
      complication following an extracapsular hip fracture. Although it can occur
      following fixation of unstable 3-part or 4-part intertrochanteric fractures with
      significant posteromedial and posterolateral comminution, it remains a rare
      complication. We present a case of AVN of the femoral head following fixation of
      a stable 2-part intertrochanteric fracture in spite of good healing at the hip
      fracture site. This is a rare but eminently treatable cause of persisting hip
      pain after hip fracture surgery, and primary or secondary care physicians should
      be aware of this possibility. 

PMID- 24319619
TI  - Factors associated with emergency department length of stay for patients with hip
      fracture.
AB  - Time to surgery, which includes time in the emergency department (ED), is
      important for all patients with hip fracture. We hypothesized that patients with
      hip fracture spend significantly more time in the ED than do patients with the
      top 5 most common conditions. In addition, we hypothesized that there are
      patient, physician, and hospital factors that affect the length of time spent in
      the ED. We retrospectively reviewed our institution's hip fracture database and
      identified 147 elderly patients with hip fractures who presented to our ED from
      December 18, 2005, through April 30, 2009. We reviewed their records for patient,
      practitioner, and hospital factors of interest associated with ED time and for 6
      specified time intervals. Average working, boarding (waiting for an inpatient
      room), and total times were calculated and compared with respective averages for
      admitted ED patients with the top 5 most common conditions. Univariate and
      multivariate analyses were performed before and after adjusting for confounders
      (significance, P = .05). The mean total ED time (7 hours and 25 minutes) and
      working time (4 hours and 31 minutes) for patients with hip fracture were similar
      to the respective overall averages for admitted ED patients. However, the average
      boarding time for patients with hip fracture was 2 hours 44 minutes, longer than
      that for other patients admitted through the ED. Factors significantly associated
      with longer ED times were a history of hypertension, history of atrial
      fibrillation, the number of computed tomography scans ordered, and the occupancy
      rate. Admission to the hip fracture service decreased working time but not
      overall time. Substantial multidisciplinary work among the ED, hospital admission
      services, and physicians is needed to dramatically decrease the boarding time and
      thus the overall time to surgery. 

PMID- 24319620
TI  - Failure of cement-augmented pedicle screws in the osteoporotic spine: a case
      report.
AB  - The treatment of patients with osteoporosis and spinal abnormalities that require
      surgical intervention is difficult because of the challenge of achieving fixation
      in osteoporotic bone. As the population ages, this challenge is becoming a common
      problem in the field of spinal surgery. Although numerous publications exist
      about the biomechanical benefits of various fixation devices and techniques, no
      standard of care has emerged that offers a clear method for accomplishing spinal
      stabilization in such patients. This case presents the failure mode of cement
      augmented pedicle screws in a patient with severe osteoporosis, a description of
      the methods used to attain fixation and spinal stability during the revision
      surgery, and the outcome achieved for the patient 1 year after surgery. An 82
      year-old female with a T9 burst fracture and a history of osteoporosis underwent
      minimally invasive instrumentation from T5 to T12, fusion from T7 to T11, and
      decompression from T8 to T10. Four weeks after surgery, the patient returned to
      the hospital because of back pain. Imaging studies showed that the pedicle screws
      at T11 and T12, which were augmented with polymethylmethacrylate (PMMA), had
      pulled out of the vertebral bodies. The pedicle screws failed by disengaging from
      the PMMA and displacing posteriorly and inferiorly. The PMMA did not appear to
      move during this process. A revision surgery was performed, in which the
      posterior construct was extended caudally and cephalad, the pedicle screws were
      augmented with PMMA, and a titanium hook and woven polyester band were used to
      increase the points of fixation. At 1-year follow-up after revision, our patient
      showed radiographic evidence of fusion, and the construct continued to maintain
      stability in the osteoporotic spine. 

PMID- 24319621
TI  - Patients' response toward an automated orthopedic osteoporosis intervention
      program.
AB  - Osteoporosis is overshadowed in an era of chronic illnesses, and a care gap
      exists between physicians and patients. The aim of this study was to determine
      the effectiveness of implementing an automated system for identifying and sending
      a letter to patients at high risk for osteoporosis. Patients 50 years of age and
      older were tagged with an International Classification of Diseases, Ninth
      Revision, diagnostic code upon initial visit to the emergency department (ED),
      identifying potential fragility fractures. Automatically generated letters were
      sent via our osteoporosis database system to each patient 3 months after the
      initial visit to the ED. The letter indicated that he or she was at risk for
      osteoporosis and suggested that the patient schedule a follow-up appointment with
      a physician. Patients were subsequently telephoned 3 months after receiving the
      letter and asked about their current plan for follow-up. The control group did
      not receive a letter after departure from the ED. In the control group, 84
      (85.71%) individuals of the total 98 did not have any follow-up but the remaining
      14 (14.29%) sought a follow-up. In the intervention group, 62 (60.19%)
      individuals of 103 did schedule a follow-up, while the remaining 41 (39.81%) did
      not seek a follow-up. Thus, the patient follow-up response rate after fracture
      treatment improved with intervention (P < .0001). Current literature has
      demonstrated the low rate of follow-up care addressing osteoporosis in patients
      experiencing fragility fractures (1%-25% without intervention). Research has
      shown the effectiveness of various types of intervention programs for improving
      the continuum of care for these high-risk patients. Nonautomated intervention
      programs can have a multitude of human-related system failures in identifying
      these patients. Our study successfully implements an automated system that is
      able to be applied to most hospitals with minimal cost and resources. 

PMID- 24319622
TI  - Aldehyde Decarbonylases: Enigmatic Enzymes of Hydrocarbon Biosynthesis.

PMID- 24319623
TI  - Temporal Trends and Changing Racial/ethnic Disparities in Alcohol Problems:
      Results from the 2000 to 2010 National Alcohol Surveys.
AB  - BACKGROUND: Economic conditions and drinking norms have been in considerable flux
      over the past 10 years. Accordingly, research is needed to evaluate both overall
      trends in alcohol problems during this period and whether changes within
      racial/ethnic groups have affected racial/ethnic disparities. METHODS: We used 3
      cross-sectional waves of National Alcohol Survey data (2000, 2005, and 2010) to
      examine a) temporal trends in alcohol dependence and consequences overall and by
      race/ethnicity, and b) the effects of temporal changes on racial/ethnic
      disparities. Analyses involved bivariate tests and multivariate negative binomial
      regressions testing the effects of race/ethnicity, survey year, and their
      interaction on problem measures. RESULTS: Both women and men overall showed
      significant increases in dependence symptoms in 2010 (vs. 2000); women also
      reported increases in alcohol-related consequences in 2010 (vs. 2000). (Problem
      rates were equivalent across 2005 and 2000.) However, increases in problems were
      most dramatic among Whites, and dependence symptoms actually decreased among
      Latinos of both genders in 2010. Consequently, the long-standing disparity in
      dependence between Latino and White men was substantially reduced in 2010. Post
      hoc analyses suggested that changes in drinking norms at least partially drove
      increased problem rates among Whites. CONCLUSIONS: Results constitute an
      important contribution to the literature on racial/ethnic disparities in alcohol
      problems. Findings are not inconsistent with the macroeconomic literature
      suggesting increases in alcohol problems during economic recession, but the
      pattern of effects across race/ethnicity and findings regarding norms together
      suggest, at the least, a revised understanding of how recessions affect drinking
      patterns and problems.

PMID- 24319624
TI  - Comparison of the Development Diabetic Induced Renal Disease in Strains of Goto
      Kakizaki Rats.
AB  - This study compared temporal changes in renal hemodynamics, proteinuria and the
      development of renal disease in Goto-Kakizaki (GK) type II diabetic rats that are
      resistant to the development of diabetic nephropathy and a genetically modified
      GK substrain (T2DN) carrying the mitochondrial genome and other alleles from Fawn
      hooded-hypertensive (FHH) rats is more susceptible to the development of renal
      injury. Both GK and T2DN rats were diabetic (>250 mg/ dL) and blood glucose
      levels were not significantly different at 3, 6 and 18 months of age. Blood
      pressure was also similar in both strains at all 3 ages. Renal blood flow (RBF)
      was 45% higher in 3 month old T2DN rats than GK rats but glomerular filtration
      rate (GFR) was similar. T2DN rats exhibited a progressive increase in proteinuria
      from 41 +/- 2 to 524 +/- 50 mg/day and 57% fall in GFR as they aged from 3 to 18
      months of age. In contrast, proteinuria only increased to 162 +/- 31 mg/day in GK
      rats and GFR remained unaltered. The kidneys from 18 month old T2DN rats
      exhibited severe glomerulosclerosis, interstitial fibrosis and tubular necrosis
      while kidneys from GK rats did not. Plasma creatinine levels were 2.4 fold higher
      in 18 month old T2DN than in GK rats. These data demonstrate that T2DN rats
      develop most of the features of diabetic nephropathy including progressive
      proteinuria and chronic kidney disease whereas the closely related GK strain does
      not, even though blood pressure and the level of hyperglycemia are similar.

PMID- 24319625
TI  - A Parametric Survival Model When a Covariate is Subject to Left-Censoring.
AB  - PROBLEM STATEMENT: Modeling survival data with a set of covariates usually
      assumes that the values of the covariates are fully observed. However, in a
      variety of applications, some values of a covariate may be left-censored due to
      inadequate instrument sensitivity to quantify the biospecimen. When data are left
      censored, the true values are missing but are known to be smaller than the
      detection limit. The most commonly used ad-hoc method to deal with nondetect
      values is to substitute the nondetect values by the detection limit. Such ad-hoc
      analysis of survival data with an explanatory variable subject to left-censoring
      may provide biased and inefficient estimators of hazard ratios and survivor
      functions. METHOD: We consider a parametric proportional hazards model to analyze
      time-to-event data. We propose a likelihood method for the estimation and
      inference of model parameters. In this likelihood approach, instead of replacing
      the nondetect values by the detection limit, we adopt a numerical integration
      technique to evaluate the observed data likelihood in the presence of a left
      censored covariate. Monte Carlo simulations were used to demonstrate various
      properties of the proposed regression estimators including the consistency and
      efficiency. RESULTS: The simulation study shows that the proposed likelihood
      approach provides approximately unbiased estimators of the model parameters. The
      proposed method also provides estimators that are more efficient than those
      obtained under the ad-hoc method. Also, unlike the ad-hoc estimators, the
      coverage probabilities of the proposed estimators are at their nominal level.
      Analysis of a large cohort study, genetic and inflammatory marker of sepsis
      study, shows discernibly different results based on the proposed method.
      CONCLUSION: Naive use of detection limit in a parametric survival model may
      provide biased and inefficient estimators of hazard ratios and survivor
      functions. The proposed likelihood approach provides approximately unbiased and
      efficient estimators of hazard ratios and survivor functions.

PMID- 24319626
TI  - Cell-Based Therapies as an Adjunct to Revascularization in Experimental
      Atherosclerotic Reno Vascular Disease.

PMID- 24319627
TI  - Nutritional Supplement-5 with a Combination of Proteasome Inhibitors
      (Resveratrol, Quercetin, delta-Tocotrienol) Modulate Age-Associated Biomarkers
      and Cardiovascular Lipid Parameters in Human Subjects.
AB  - BACKGROUND: Age-associated altered redox imbalances and dysregulated immune
      function, contribute to the development of a variety of age associated diseases.
      Inflammatory markers and lipid profiles are useful prognostic indicators of a
      variety of age-associated and cardiovascular diseases. We have previously studied
      the impact of several proteasome inhibitors on several markers of inflammation
      and lipid profiles in vitro, in vivo, in cell lines, animal models, and in human
      subjects. The current study represents an extension of this work. Our main
      hypothesis is that a combination of various naturally-occurring proteasome
      inhibitors, which inhibits nitric oxide (NO), and C-reactive protein (CRP)
      mediated inflammation, will have better efficacy in the prevention and treatment
      of age-associated disorders including cardiovascular disease. METHODS: Two double
      blind, randomized, placebo-controlled cross-over trials were conducted to
      determine the impact of a mixture of NS-5 (resveratrol, pterostilbene, quercetin,
      delta-tocotrienol, nicotinic acid) on serum NO, CRP, gamma-glutamyl-transferase
      (gamma-GT) activity, total antioxidant status (TAS), total cholesterol, LDL
      cholesterol, HDL-cholesterol and triglycerides levels. Healthy seniors (Group-1;
      n = 32) free-living (A, B; 16/group), and hypercholesterolemic (Group-2; n = 64)
      subjects on AHA-Step-1-diet were divided into two groups (C, D; 32/group).
      Baseline levels were established for parameters as mentioned above. Groups A, C
      were administered 4-capsules/d of NS-5 and groups B, D, placebo (starch) for 6
      weeks. Groups were crossed-over, followed by a 2-week wash-out period. Groups A,
      C were given 4-capsules/d of placebo and groups B, D, 4-capsules/d of NS-5 for 6
      weeks. Groups C, D were continued on AHA-Step-1-diet. RESULTS: All the subjects
      completed each phase in both studies without any complaints. There were
      significant ( P < 0.01 - 0.05) decreases in the serum levels of NO (30%, 26%),
      CRP (29%, 21%), gamma-GT activity (14%, 17%), and blood pressure
      (systolic/diastolic, 3/6%, 3/3%) of Groups A and B, respectively, of free-living
      healthy seniors without affecting the total, HDL-, LDL-cholesterol or
      triglycerides compared to their respective baseline values. However, serum levels
      of NO (36%, 43%), CRP (31%, 48%), gamma-GT (17%, 20%), total cholesterol (19%,
      15%), LDL-cholesterol (28%, 20%), triglycerides (11%, 18%) of Groups C and D were
      significantly ( P < 0.01-0.05) decreased with NS-5 treatment of
      hypercholesterolemic subjects compared to baseline values, without affecting the
      serum HDL-cholesterol levels. The serum levels of total antioxidant status (TAS)
      were increased (10%, 14%; P < 0.05) in Groups A and B, increased (19%, 24%; P <
      0.02), and blood pressure (systolic/diastolic, 5/6%, 3/5%) in Groups C and D with
      NS-5 treatment, compared to respective baseline values. CONCLUSIONS: The
      consumption of NS-5 mixture decreased significantly serum NO, CRP and gamma-GT
      levels, improved TAS and lipid profiles at risk cardiovascular and hold promise
      for delaying onset of age-associated diseases.

PMID- 24319629
TI  - Improved Adeno-associated Viral Gene Transfer to Murine Glioma.
AB  - Glioblastoma (GBM) is a deadly primary brain tumor. Current treatment, consisting
      of surgical removal of the tumor mass followed by chemotherapy and/or
      radiotherapy, does not significantly prolong survival. Gene therapies for GBM are
      being developed in clinical trials, for example using adenoviral vectors. While
      adeno-associated virus (AAV) represents an alternative vector system, limited
      gene transfer to glioma cells has hampered its use. Here, we evaluated newly
      emerged variants of AAV capsid for gene delivery to murine glioma. We tested a
      mutant AAV2 capsid devoid of 3 surface-exposed tyrosine residues, AAV2 (Y444-500
      730F), and a "shuffed" capsid (ShH19, containing sequences from several
      serotypes) that had previously been selected for enhanced glial gene delivery.
      AAV2 (Y-F) and ShH19 showed improved transduction of murine glioma GL261 cells in
      vitro by 2- to 6-fold, respectively, over AAV2. While AAV2 gene transfer to GL261
      cells in established tumors in brains of syngeneic mice was undetectable,
      intratumoral injection of AAV2 (Y-F) or ShH19 resulted in local transduction of
      approximately 10% of tumor cells. In addition, gene transfer to neurons adjacent
      to the tumor was observed, while microglia were rarely transduced. Use of self
      complementary vectors further increased transduction of glioma cells. Together,
      the data demonstrate the potential for improved AAV-based gene therapy for glioma
      using recently developed capsid variants.

PMID- 24319628
TI  - Angiogenic Factors and Cytokines in Diabetic Retinopathy.
AB  - Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and
      type-2 diabetes. The recent success of treatments inhibiting the function of
      vascular endothelial growth factor (VEGF) demonstrates that specific targeting of
      a growth factor responsible for vascular permeability and growth is an effective
      means of treating DR-associated vascular dysfunction, edema and angiogenesis.
      This has stimulated research of alternative therapeutic targets involved in the
      control of retinal vascular function. However, additional treatment options and
      preventative measures are still needed and these require a greater understanding
      of the pathological mechanisms leading to the disturbance of retinal tissue
      homeostasis in DR. Although severe DR can be treated as a vascular disease,
      abundant data suggests that inflammation is also occurring in the diabetic
      retina.Thus, anti-inflammatory therapies may also be useful for treatment and
      prevention of DR. Herein, the evidence for altered expression of angiogenic
      factors and cytokines in DR is reviewed and possible mechanisms by which the
      expression of VEGF and cytokines may be increased in the diabetic retina are
      examined. In addition, the potential role for microglial activation in diabetic
      retinal neuroinflammation is explored.

PMID- 24319630
TI  - Ectopic platelet-delivered factor (F) VIII for the treatment of Hemophilia A:
      Plasma and platelet FVIII, is it all the same?
AB  - Hemophilia A is the most common inherited bleeding diathesis and is due to a
      deficiency of functional coagulation factor (F) VIII. Most patients have a severe
      deficiency and require a program of prophylactic plus acute infusions of
      recombinant FVIII to prevent significant joint and other target organ damage. One
      of the greatest challenges remaining in the care of these patients is that one
      fifth to third of the patients develop inhibitors to the infused proteins. While
      a significant portion of such inhibitors can be either overcome or the inhibitors
      eliminated, some patients with persistent and significant titers of inhibitors
      need to rely on second tier therapies that are not as effective at preventing
      significant bleeding morbidity or mortality. A number of groups have been
      developing therapeutic strategies for FVIII gene therapy for this disorder.
      Virtually all of these therapies have in common a rise in the plasma level of
      FVIII, and interpretation of their efficacy is straightforward related to levels
      achieved. However, several groups have also shown that FVIII can be ectopically
      expressed in developing megakaryocytes, where although plasma FVIII levels remain
      undetectable, this FVIII can be released and be effective at sites of platelet
      activation. Moreover, it is clear that this platelet (p) FVIII is protected to a
      degree from inhibitors, making pFVIII a particularly attractive strategy for gene
      therapy for hemophilia A. Yet at the same time, we have shown that pFVIII has a
      different availability and distribution in a growing thrombus than plasma FVIII.
      The clinical implications and challenges of these findings as murine and canine
      hemophilia A preclinical studies go forward with pFVIII are discussed.

PMID- 24319631
TI  - Systems and Network Pharmacology Approaches to Cancer Stem Cells Research and
      Therapy.
AB  - The cancer stem cell (CSC) hypothesis is increasingly being accepted as a model
      to explain for the functional heterogeneity that is commonly observed in solid
      tumors. According to this hypothesis, there exists a hierarchical organization of
      cells within the tumor, in which a differential subpopulation of stem-like cells
      is responsible for sustaining and recurrence of tumor growth. CSCs have been
      shown to exist in a variety of solid tumors especially those with known resistant
      phenotypes such as breast, prostate and pancreatic adenocarcinoma (PDAC). In all
      these models, the commonality of deregulation of three crucial pathways; Wnt,
      notch and hedgehog that maintain CSC self-renewal capacity is emerging.
      Collectively these major pathways and have been linked to the observed resistance
      of CSC to chemotherapy and radiotherapy. The existing lack of knowledge and our
      incomplete understanding of the molecular signatures associated with CSCs
      highlight the need for better approaches in both isolation and identification of
      unique pathways associated with these cells. In this direction, computational
      biology, especially systems and network approaches, have proven to be of great
      utility in unraveling pathway complexities such as those associated with CSCs.
      With highlights on the most up-to-date molecular, network, cellular, clinical,
      and therapeutic cancer research findings, this article tends to provide a wealth
      of insights on systems and network biology approaches to CSC marker
      identification, the mechanism through which they evade treatment as well as
      therapeutic approaches that will help in conquering these elusive cells in
      incurable and refractory malignancies.

PMID- 24319632
TI  - Cancer-associated fibroblasts and macrophages: Friendly conspirators for
      malignancy.
AB  - Inflammation, which is now recognized as an hallmark of cancer, is intimately
      linked to the reactivity of stromal fibroblasts. Accumulating evidence indicate
      that cancer-associated fibroblasts not only drive the epithelial-mesenchymal
      transition and metabolically sustain the growth of cancer cells, but also engage
      in a reciprocal relationship with M2 macrophages that dramatically boost
      malignancy.

PMID- 24319633
TI  - Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor
      infiltrating lymphocytes for adoptive T-cell therapy.
AB  - Co-stimulation through members of the tumor necrosis factor receptor (TNFR)
      family appears to be critical for the generation of T cells with optimal effector
      memory properties for adoptive cell therapy. Our work suggests that continuous 4
      1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal
      therapeutic profile and that the administration of 4-1BB agonists upon adoptive
      cell transfer further improves antitumor T-cell functions.

PMID- 24319635
TI  - Mutations in glioblastoma oncosuppressive pathways pave the way for
      oncomodulatory activity of cytomegalovirus.
AB  - Over the last decade, cytomegalovirus (CMV) has been suggested to promote the
      development of glioblastoma multiforme (GBM). Recent evidence demonstrates that
      CMV contributes to the progression of GBM in the context of oncosuppressor gene
      mutations. This finding provides further insights into the mechanisms whereby CMV
      exacerbates the malignancy of GBM.

PMID- 24319636
TI  - Zoledronate-pulsed dendritic cell-based anticancer vaccines.
AB  - The addition of zoledronate to tumor-associated antigen (TAA)-loaded dendritic
      cells (DCs) promotes the activation of interferon gamma-secreting Vgamma9
      gammadelta T cells, in turn eliciting TAA-specific CD8+ T-cell responses.
      Immunological responses induced by zoledronate-pulsed DC-based vaccines have been
      associated with therapeutic effects in clinical trials.

PMID- 24319637
TI  - Radiation-induced tumor dormancy reflects an equilibrium between the
      proliferation and T lymphocyte-mediated death of malignant cells.
AB  - Despite its efficacy and widespread use, radiation therapy is often associated
      with local or distal tumor relapse. We have recently found that CD8+ T cells and
      their cytokines are essential for maintaining irradiated neoplasms under control.
      In line with this notion, enhancing T-cell functions by means of immune
      checkpoint inhibitors can tilt the balance toward tumor rejection.

PMID- 24319638
TI  - CX3CL1 at the crossroad of EGF signals: Relevance for the progression of ERBB2+
      breast carcinoma.
AB  - Inflammatory mediators can play a dual role in oncogenesis and tumor progression.
      CX3CL1, a chemokine previously implicated in natural killer cell- and CD8+ T cell
      mediated antitumor immune responses, has now been identified as a promoter of
      ERBB2-expressing breast carcinomas as it cross-activates members of the epidermal
      growth factor receptor family.

PMID- 24319634
TI  - Trial Watch: Anticancer radioimmunotherapy.
AB  - Radiotherapy has extensively been employed as a curative or palliative
      intervention against cancer throughout the last century, with a varying degree of
      success. For a long time, the antineoplastic activity of X- and gamma-rays was
      entirely ascribed to their capacity of damaging macromolecules, in particular
      DNA, and hence triggering the (apoptotic) demise of malignant cells. However,
      accumulating evidence indicates that (at least part of) the clinical potential of
      radiotherapy stems from cancer cell-extrinsic mechanisms, including the
      normalization of tumor vasculature as well as short- and long-range bystander
      effects. Local bystander effects involve either the direct transmission of lethal
      signals between cells connected by gap junctions or the production of diffusible
      cytotoxic mediators, including reactive oxygen species, nitric oxide and
      cytokines. Conversely, long-range bystander effects, also known as out-of-field
      or abscopal effects, presumably reflect the elicitation of tumor-specific
      adaptive immune responses. Ionizing rays have indeed been shown to promote the
      immunogenic demise of malignant cells, a process that relies on the
      spatiotemporally defined emanation of specific damage-associated molecular
      patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of
      other treatment modalities such as surgery (both in neo-adjuvant and adjuvant
      settings) or chemotherapy. Moreover, at least under some circumstances,
      radiotherapy may potentiate anticancer immune responses as elicited by various
      immunotherapeutic agents, including (but presumably not limited to)
      immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell
      based interventions and Toll-like receptor agonists. Here, we review the
      rationale of using radiotherapy, alone or combined with immunomodulatory agents,
      as a means to elicit or boost anticancer immune responses, and present recent
      clinical trials investigating the therapeutic potential of this approach in
      cancer patients.

PMID- 24319639
TI  - Improving macrophage responses to therapeutic antibodies by molecular engineering
      of SIRPalpha variants.
AB  - CD47 transduces inhibitory signals through signal-regulatory protein alpha
      (SIRPalpha), a plasma membrane receptor expressed by macrophages. Many cancers
      upregulate CD47 to evade immunosurveillance. We have recently engineered
      SIRPalpha variants that potently antagonize CD47 for use as anticancer
      immunotherapeutics. These high-affinity SIRPalpha variants synergize with
      antineoplastic antibodies by lowering the threshold for macrophage-mediated
      destruction of malignant cells.

PMID- 24319640
TI  - A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel
      adenosinergic loop in human T lymphocytes.
AB  - The tumor microenvironment is characterized by of high levels of extracellular
      nucleotides that are metabolized through the dynamic and sequential action of
      cell surface enzymes (ectoenzymes). These ectoenzymes operate according to their
      spatial arrangement, as part of (1) continuous (molecules on the same cell) or
      (2) discontinuous (molecules on different cells) pathways, the latter being
      facilitated by restricted cellular microenvironment. The outcome of this
      catabolic activity is an increase in the local concentration of adenosine, a
      nucleoside involved in the control of inflammation and immune responses. The aim
      of the work presented here was to demonstrate that a previously unexplored
      enzymatic pathway may be an alternate route to produce extracellular adenosine.
      Our data show that this new axis is driven by the nucleotide-metabolizing
      ectoenzymes CD38 (an NAD+ nucleosidase), the ecto-nucleotide
      pyrophosphatase/phosphodiesterase 1 (NPP1, also known as CD203a or PC-1) and the
      5' ectonucleotidase (5'-NT) CD73, while bypassing the canonical catabolic pathway
      mediated by the nucleoside tri- and diphosphohydrolase (NTPDase) CD39. To
      determine the relative contributions of these cell surface enzymes to the
      production of adenosine, we exploited a human T-cell model allowing for the
      modular expression of the individual components of this alternative pathway upon
      activation and transfection. The biochemical analysis of the products of these
      ectoenzymes by high-performance liquid chromatography (HPLC) fully substantiated
      our working hypothesis. This newly characterized pathway may facilitate the
      emergence of an adaptive immune response in selected cellular contexts.
      Considering the role for extracellular adenosine in the regulation of
      inflammation and immunogenicity, this pathway could constitute a novel strategy
      of tumor evasion, implying that these enzymes may represent ideal targets for
      antibody-mediated therapy.

PMID- 24319641
TI  - Interventions to Improve Walking in Older Adults.
AB  - Interventions to improve walking in older adults have historically been
      multifactorial (i.e. strengthening, endurance and flexibility programs) focusing
      on improving the underlying impairments. These impairment-based programs have
      resulted in only modest improvements in walking. In older adults, walking is
      slow, less stable, inefficient, and the timing and coordination of stepping with
      postures and phases of gait is poor. We argue the timing and coordination
      problems are evidence of the loss of motor skill in walking. Taking a lesson from
      the sports world and from neurorehabilitation, task-oriented motor learning
      exercise is an essential component of training to improve motor skill and may be
      a beneficial approach to improving walking in older adults. In this article we:
      1) briefly review the current literature regarding impairment-based interventions
      for improving mobility, 2) discuss why the results have been only modest, and 3)
      suggest an alternative approach to intervention (i.e. task oriented motor
      learning).

PMID- 24319642
TI  - Aging, circadian rhythms and depressive disorders: a review.
AB  - INTRODUCTION: Aging is typically associated with impairing behavioral patterns
      that are frequently and inappropriately seen as normal. Circadian rhythm changes
      and depressive disorders have been increasingly proposed as the two main
      overlapping and interpenetrating changes that take place in older age. This study
      aims to review the state of the art on the subject concerning epidemiology,
      pathophysiological mechanism, clinical findings and relevance, as well as
      available treatment options. MATERIALS AND METHODS: A nonsystematic review of all
      English language PubMed articles published between 1995 and December 2012 using
      the terms "circadian rhythms", "mood disorders", "depression", "age", "aging",
      "elderly" and "sleep". DISCUSSION AND CONCLUSION: Sleep disorders, mainly
      insomnia, and depression have been demonstrated to be highly co-prevalent and
      mutually precipitating conditions in the elderly population. There is extensive
      research on the pathophysiological mechanisms through which age conditions
      circadian disruption, being the disruption of the Melatonin system one of the
      main changes. However, research linking clearly and unequivocally circadian
      disruption and mood disorders is still lacking. Nonetheless, there are
      consistently described molecular changes on shared genes and also several
      proposed pathophysiological models linking depression and sleep disruption, with
      clinical studies also suggesting a bi-directional relationship between these
      pathologies. In spite of this suggested relation, clinical evaluation of these
      conditions in elderly patients consistently reveals itself rather complicated due
      to the frequently co-existing co-morbidities, some of them having been
      demonstrated to alter sleep and mood patters. This is the case of strokes, forms
      of dementia such as Alzheimer and Parkinson, several neurodegenerative disorders,
      among others. Although there are to the present no specific treatment guidelines,
      available treatment options generally base themselves on the premise that
      depression and sleep disturbances share a bidirectional relationship and so, the
      adoption of measures that address specifically one of the conditions will
      reciprocally benefit the other. Treatment options range from Cognitive Behavioral
      Therapy, Chronotherapy, and Light therapy, to drugs such as Melatonin/Melatonin
      agonists, antidepressants and sedatives.

PMID- 24319644
TI  - Diversity of pathological features other than Lewy bodies in familial Parkinson's
      disease due to SNCA mutations.
AB  - The clinical features of the genetically determined forms of familial Parkinson's
      disease (PD) have been described in multiple reports, but there have been few
      comparative neuropathologic studies. Five familial PD cases, with mutations in
      SNCA, were matched for age, sex, and Alzheimer type pathology with sporadic PD
      cases. Immunohistochemistry for phospho-tau and alpha-synuclein was performed in
      8 brain regions. The frequency of tau pathology and the morphologic features of
      alpha-synuclein pathology in familial PD were compared with sporadic PD using
      semi-quantitative methods. In familial PD, there were significantly more tau
      positive extra-perikaryal spheroid-like and thread-like lesions than in the
      sporadic PD. There was no significant difference in the amount of alpha-synuclein
      positive neuronal perikaryal pathology between familial PD and sporadic PD, but
      alpha-synuclein positive oligodendroglial and neuritic lesions were significantly
      greater in familial PD compared to sporadic PD. In the substantia nigra, familial
      PD had more marked neuronal loss and fewer residential neurons with Lewy bodies
      than the sporadic PD, suggesting a close relationship between the severity of
      neuronal loss and Lewy body formation. The results show a diversity of
      pathological features of genetically determined familial PD, and they draw
      attention to the possible role of tau protein in neurodegeneration. Moreover, the
      presence of oligodendroglial inclusions at the light and electron microscopic
      levels in familial PD suggests that PD and multiple system atrophy form a
      continuum of alpha-synuclein pathology. 

PMID- 24319643
TI  - ER-stress in Alzheimer's disease: turning the scale?
AB  - Pathogenic mechanisms of Alzheimer's disease (AD) are intensely investigated as
      it is the most common form of dementia and burdens society by its costs and
      social demands. While key molecules such as A-beta peptides and tau have been
      identified decades ago, it is still enigmatic what drives the disease in its
      sporadic manifestation. Synthesis of A-beta peptides as well as phosphorylation
      of tau proteins comprise normal cellular functions and occur in principle in the
      healthy as well as in dementia-affected persons. Dyshomeostasis of Amyloid
      Precursor Protein (APP) cleavage, energy metabolism or kinase/phosphatase
      activity due to stressors has been suggested as a trigger of the disease. One way
      for cells to escape stress based on dysfunction of ER is the unfolded protein
      response - the UPR. This pathway is composed out of three different routes that
      differ in proteins involved, targets and consequences for cell fate: activation
      of transmembrane ER resident kinases IRE1-alpha and PERK or monomerization of
      membrane-anchored activating transcription factor 6 (ATF6) induce activation of
      versatile transcription factors (XBP-1, eIF2-alpha/ATF4 and ATF6 P50). These bind
      to specific DNA sequences on target gene promoters and on one hand attenuate
      general ER-prone protein synthesis and on the other equip the cell with tools to
      de-stress. If cells fail in stress compensation, this signaling also is able to
      evoke apoptosis. In this review we summarized knowledge on how APP processing and
      phosphorylation of tau might be influenced by ER-stress signaling. In addition,
      we depicted the effects UPR itself seems to have on molecules closely related to
      AD and describe what is known about UPR in AD animal models as well as in human
      patients. 

PMID- 24319645
TI  - Frontotemporal dementia with a C9ORF72 expansion in a Swedish family: clinical
      and neuropathological characteristics.
AB  - BACKGROUND: In 2011 the C9ORF72 repeat expansion was identified as the most
      frequent genetic mutation underlying FTD and ALS. The main aim of this study was
      to investigate clinical characteristics in a large C9ORF72-positive FTD family,
      and to compare these with the neuropathological findings. METHODS: The clinical
      records of 12 related FTD patients were thoroughly evaluated. The five
      neuropathologically examined cases were revised using additional TDP-43 immuno
      stainings. Four cases were screened for the C9ORF72 expansion. RESULTS: All 12
      patients fulfilled the criteria for bvFTD. Restlessness and social neglect were
      often among the first reported symptoms. Psychotic symptoms were reported in 8
      patients. Somatic complaints were seen in 7 cases. All the neuropathologically
      examined cases were TDP-43 positive. CONCLUSIONS: The phenotype of this C9ORF72
      hexanucleotide expansion carrier family was bvFTD. The clinical symptom profile
      was strikingly homogenous. Psychotic symptoms and somatic complaints were
      observed in most of the cases.

PMID- 24319646
TI  - GWAS risk factors in Parkinson's disease: LRRK2 coding variation and genetic
      interaction with PARK16.
AB  - Parkinson's disease (PD) is a multifactorial movement disorder characterized by
      progressive neurodegeneration. Genome-wide association studies (GWAS) have
      nominated over fifteen distinct loci associated with risk of PD, however the
      biological mechanisms by which these loci influence disease risk are mostly
      unknown. GWAS are only the first step in the identification of disease genes: the
      specific causal variants responsible for the risk within the associated loci and
      the interactions between them must be identified to fully comprehend their impact
      on the development of PD. In the present study, we first attempted to replicate
      the association signals of 17 PD GWAS loci in our series of 1381 patients with PD
      and 1328 controls. BST1, SNCA, HLA-DRA, CCDC62/HIP1R and MAPT all showed a
      significant association with PD under different models of inheritance and LRRK2
      showed a suggestive association. We then examined the role of coding LRRK2
      variants in the GWAS association signal for that gene. The previously identified
      LRRK2 risk mutant p.M1646T and protective haplotype p.N551K-R1398H-K1423K did not
      explain the association signal of LRRK2 in our series. Finally, we investigated
      the gene-gene interaction between PARK16 and LRRK2 that has previously been
      proposed. We observed no interaction between PARK16 and LRRK2 GWAS variants, but
      did observe a non-significant trend toward interaction between PARK16 and LRRK2
      variants within the protective haplotype. Identification of causal variants and
      the interactions between them is the crucial next step in making biological sense
      of the massive amount of data generated by GWAS studies. Future studies combining
      larger sample sizes will undoubtedly shed light on the complex molecular
      interplay leading to the development of PD. 

PMID- 24319647
TI  - Differences between early and late onset Alzheimer's disease.
AB  - Previous studies comparing early-onset Alzheimer's disease (EOAD) and late-onset
      AD (LOAD) have been limited by cross-sectional design and a focus on isolated
      clinical variables. This study aims to explore differentials in clinical features
      between EOAD and LOAD and to examine longitudinally trends in cognitive function.
      Data from 3,747 subjects with AD from C-Path Online Data Repository was used to
      compare demographics, body mass index (BMI), mean arterial pressure (MAP),
      biochemistry and cognitive assessments, including mini-mental state examination
      (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog),
      between EOAD and LOAD. The baseline differences were examined by binominal
      proportion test and t-test. The trends of cognitive functions, evaluating by MMSE
      and ADAS-Cog, were examined by the mixed model, controlling for the effect of
      repeated measures of the same person. No significant difference was found in BMI
      and MAP. C-reactive protein, creatinine and blood urea nitrogen (BUN) (p<0.05)
      were significantly higher in LOAD. The APOE epsilon4 alleles was more likely to
      be found among LOAD compared to APOE epsilon2 or APOE epsilon3. EOAD had
      significantly lower MMSE at baseline and this difference significantly increased
      over time. Despite an insignificant differential in ADAS-Cog between EOAD and
      LOAD at baseline, the differential was enlarged gradually and became more
      significant with time. Our findings suggest that elevated inflammatory markers,
      impaired renal function and APOE epsilon4 alleles are overrepresented in LOAD,
      possibly indicating that different factors determine the development of EOAD and
      its more rapid cognitive deterioration. 

PMID- 24319648
TI  - Matrix Producing Cells in Chronic Kidney Disease: Origin, Regulation, and
      Activation.
AB  - Chronic injury to the kidney causes kidney fibrosis with irreversible loss of
      functional renal parenchyma and leads to the clinical syndromes of chronic kidney
      disease (CKD) and end-stage renal disease (ESRD). Regardless of the type of
      initial injury, kidney disease progression follows the same pathophysiologic
      processes characterized by interstitial fibrosis, capillary rarefaction and
      tubular atrophy. Myofibroblasts play a pivotal role in fibrosis by driving
      excessive extracellular matrix (ECM) deposition. Targeting these cells in order
      to prevent the progression of CKD is a promising therapeutic strategy, however,
      the cellular source of these cells is still controversial. In recent years, a
      growing amount of evidence points to resident mesenchymal cells such as pericytes
      and perivascular fibroblasts, which form extensive networks around the renal
      vasculature, as major contributors to the pool of myofibroblasts in renal
      fibrogenesis. Identifying the cellular origin of myofibroblasts and the key
      regulatory pathways that drive myofibroblast proliferation and
      transdifferentiation as well as capillary rarefaction is the first step to
      developing novel anti-fibrotic therapeutics to slow or even reverse CKD
      progression and ultimately reduce the prevalence of ESRD. This review will
      summarize recent findings concerning the cellular source of myofibroblasts and
      highlight recent discoveries concerning the key regulatory signaling pathways
      that drive their expansion and progression in CKD.

PMID- 24319649
TI  - Management strategies to reduce risk of postoperative infections.
AB  - Postoperative infections, although rare, are still of great concern to the
      ophthalmologist. The incidence of post-cataract endophthalmitis is low, with a
      range of .28 per 1,000 to 2.99 per 1000. In addition to intraoperative
      considerations such as poor wound construction, vitreous loss, topical
      anesthesia, and prolonged surgical time, other risk factors include preoperative
      factors such as a diseased ocular surface and systemic immunosuppression.
      Potential methods of reducing risk of endophthalmitis after anterior segment
      surgery are discussed and available literature is summarized.

PMID- 24319650
TI  - Pathway analyses and understanding disease associations.
AB  - High throughput technologies have been applied to investigate the underlying
      mechanisms of complex diseases, identify disease-associations and help to improve
      treatment. However it is challenging to derive biological insight from
      conventional single gene based analysis of "omics" data from high throughput
      experiments due to sample and patient heterogeneity. To address these challenges,
      many novel pathway and network based approaches were developed to integrate
      various "omics" data, such as gene expression, copy number alteration, Genome
      Wide Association Studies, and interaction data. This review will cover recent
      methodological developments in pathway analysis for the detection of dysregulated
      interactions and disease-associated subnetworks, prioritization of candidate
      disease genes, and disease classifications. For each application, we will also
      discuss the associated challenges and potential future directions.

PMID- 24319651
TI  - The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream
      RNA targets in cortical neurons.
AB  - TDP-43 and FUS are linked to amyotrophic lateral sclerosis (ALS) and
      frontotemporal lobar degeneration (FTLD), and loss of function of either protein
      contributes to these neurodegenerative conditions. To elucidate the TDP-43- and
      FUS-regulated pathophysiological RNA metabolism cascades, we assessed the
      differential gene expression and alternative splicing profiles related to
      regulation by either TDP-43 or FUS in primary cortical neurons. These profiles
      overlapped by >25% with respect to gene expression and >9% with respect to
      alternative splicing. The shared downstream RNA targets of TDP-43 and FUS may
      form a common pathway in the neurodegenerative processes of ALS/FTLD. 

PMID- 24319652
TI  - Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non
      hypertrophic and non-failing transgenic mouse hearts expressing N-terminal
      truncated cardiac troponin I.
AB  - We previously reported that a restrictive N-terminal truncation of cardiac
      troponin I (cTnI-ND) is up-regulated in the heart in adaptation to hemodynamic
      stresses. Over-expression of cTnI-ND in the hearts of transgenic mice revealed
      functional benefits such as increased relaxation and myocardial compliance. In
      the present study, we investigated the subsequent effect on myocardial
      remodeling. The alpha-smooth muscle actin (alpha-SMA) isoform is normally
      expressed in differentiating cardiomyocytes and is a marker for myocardial
      hypertrophy in adult hearts. Our results show that in cTnI-ND transgenic mice of
      between 2 and 3 months of age (young adults), a significant level of alpha-SMA is
      expressed in the heart as compared with wild-type animals. Although blood vessel
      density was increased in the cTnI-ND heart, the mass of smooth muscle tissue did
      not correlate with the increased level of alpha-SMA. Instead, immunocytochemical
      staining and Western blotting of protein extracts from isolated cardiomyocytes
      identified cardiomyocytes as the source of increased alpha-SMA in cTnI-ND hearts.
      We further found that while a portion of the up-regulated alpha-SMA protein was
      incorporated into the sarcomeric thin filaments, the majority of SMA protein was
      found outside of myofibrils. This distribution pattern suggests dual functions
      for the up-regulated alpha-SMA as both a contractile component to affect
      contractility and as possible effector of early remodeling in non-hypertrophic,
      non-failing cTnI-ND hearts. 

PMID- 24319653
TI  - Mast cell deficiency results in the accumulation of preadipocytes in adipose
      tissue in both obese and non-obese mice.
AB  - Mast cells have been suggested to play key roles in adipogenesis. We herein show
      that the expression of preadipocyte, but not adipocyte, marker genes increases in
      the white adipose tissue of mast cell-deficient (Kit(W-sh/W-sh) ) mice under both
      obese and non-obese conditions. In vitro culturing with adipogenic factors
      revealed increased adipocytes differentiated from the Kit(W-sh/W-sh) stromal
      vascular fraction, suggesting the accumulation of preadipocytes. Moreover, the
      increased expression of preadipocyte genes was restored by mast cell
      reconstitution in the Kit(W-sh/W-sh) mice. These results suggest positive effects
      of mast cells on the preadipocyte to adipocyte transition under both
      physiological and pathological conditions. 

PMID- 24319654
TI  - White matter tract integrity metrics reflect the vulnerability of late
      myelinating tracts in Alzheimer's disease.
AB  - Post-mortem and imaging studies have observed that white matter (WM) degenerates
      in a pattern inverse to myelin development, suggesting preferential regional
      vulnerabilities influencing cognitive decline in AD. This study applied novel WM
      tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to
      examine WM tissue properties in AD within this framework. Using data from
      amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal
      control (NC; n = 15) subjects, mixed models revealed interaction effects:
      specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water
      fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e.
      superior and inferior longitudinal fasciculi) changed in the course of disease,
      but were stable in the initial stages for early-myelinating tracts (i.e.
      posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late
      myelinating tracts correlated with semantic verbal fluency, a cognitive function
      known to decline in AD. These findings corroborate the preferential vulnerability
      of late-myelinating tracts, and illustrate an application of WMTI metrics to
      characterizing the regional course of WM changes in AD. 

PMID- 24319655
TI  - Altered anterior visual system development following early monocular enucleation.
AB  - PURPOSE: Retinoblastoma is a rare eye cancer that generally occurs before 5 years
      of age and often results in enucleation (surgical removal) of the cancerous eye.
      In the present study, we sought to determine the consequences of early monocular
      enucleation on the morphological development of the anterior visual pathway
      including the optic chiasm and lateral geniculate nucleus. METHODS: A group of
      adults who had one eye enucleated early in life due to retinoblastoma was
      compared to binocularly intact controls. Although structural changes have
      previously been reported in late enucleation, we also collected data from one
      late enucleated participant to compare to our early enucleated participants.
      Measurements of the optic nerves, optic chiasm, optic tracts and lateral
      geniculate nuclei were evaluated from T1 weighted and proton density weighted
      images collected from each participant. RESULTS: The early monocular enucleation
      group exhibited overall degeneration of the anterior visual system compared to
      controls. Surprisingly, however, optic tract diameter and geniculate volume
      decreases were less severe contralateral to the remaining eye. Consistent with
      previous research, the late enucleated participant showed no asymmetry and
      significantly larger volume decreases in both geniculate nuclei compared to
      controls. CONCLUSIONS: The novel finding of an asymmetry in morphology of the
      anterior visual system following long-term survival from early monocular
      enucleation indicates altered postnatal visual development. Possible mechanisms
      behind this altered development include recruitment of deafferented cells by
      crossing nasal fibres and/or geniculate cell retention via feedback from primary
      visual cortex. These data highlight the importance of balanced binocular input
      during postnatal maturation for typical anterior visual system morphology.

PMID- 24319656
TI  - Pathomechanisms and compensatory efforts related to Parkinsonian speech.
AB  - Voice and speech in Parkinson's disease (PD) patients are classically affected by
      a hypophonia, dysprosody, and dysarthria. The underlying pathomechanisms of these
      disabling symptoms are not well understood. To identify functional anomalies
      related to pathophysiology and compensation we compared speech-related brain
      activity and effective connectivity in early PD patients who did not yet develop
      voice or speech symptoms and matched controls. During fMRI 20 PD patients ON and
      OFF levodopa and 20 control participants read 75 sentences covertly, overtly with
      neutral, or with happy intonation. A cue-target reading paradigm allowed for
      dissociating task preparation from execution. We found pathologically reduced
      striato-prefrontal preparatory effective connectivity in early PD patients
      associated with subcortical (OFF state) or cortical (ON state) compensatory
      networks. While speaking, PD patients showed signs of diminished monitoring of
      external auditory feedback. During generation of affective prosody, a reduced
      functional coupling between the ventral and dorsal striatum was observed. Our
      results suggest three pathomechanisms affecting speech in PD: While diminished
      energization on the basis of striato-prefrontal hypo-connectivity together with
      dysfunctional self-monitoring mechanisms could underlie hypophonia, dysarthria
      may result from fading speech motor representations given that they are not
      sufficiently well updated by external auditory feedback. A pathological interplay
      between the limbic and sensorimotor striatum could interfere with affective
      modulation of speech routines, which affects emotional prosody generation.
      However, early PD patients show compensatory mechanisms that could help improve
      future speech therapies. 

PMID- 24319657
TI  - Robust self-renewal of rat embryonic stem cells requires fine-tuning of glycogen
      synthase kinase-3 inhibition.
AB  - Germline-competent embryonic stem cells (ESCs) have been derived from mice and
      rats using culture conditions that include an inhibitor of glycogen synthase
      kinase 3 (GSK3). However, rat ESCs remain susceptible to sporadic
      differentiation. Here, we show that unsolicited differentiation is attributable
      to overinhibition of GSK3. The self-renewal effect of inhibiting GSK3 is mediated
      via beta-catenin, which abrogates the repressive action of TCF3 on core
      pluripotency genes. In rat ESCs, however, GSK3 inhibition also leads to
      activation of differentiation-associated genes, notably lineage specification
      factors Cdx2 and T. Lowered GSK3 inhibition reduces differentiation and enhances
      clonogenicity and self-renewal. The differential sensitivity of rat ESCs to GSK3
      inhibition is linked to elevated expression of the canonical Wnt pathway effector
      LEF1. These findings reveal that optimal GSK3 inhibition for ESC propagation is
      influenced by the balance of TCF/LEF factors and can vary between species. 

PMID- 24319658
TI  - Dissecting the roles of miR-302/367 cluster in cellular reprogramming using TALE
      based repressor and TALEN.
AB  - MicroRNAs are important gene regulators involved in many biological processes,
      including stemness maintenance and cellular reprogramming. Current methods used
      in loss-of-function studies of microRNAs mainly include locked nucleic acid (LNA)
      oligonucleotides and miRZip inhibitors, which have several limitations. Due to
      their unique gene structures and small sizes, there is no efficient or simple
      strategy to knock down or knock out microRNAs or whole microRNA clusters. Here,
      we demonstrate knockdown of the miR-302/367 cluster by using the Kruppel
      associated box repressor domain fused with specific transcription activator-like
      effectors (TALEs) designed to bind the miR-302/367 cluster promoter. We also
      designed two pairs of TALE nucleases (TALENs) to efficiently delete the miR
      302/367 cluster in primary human fibroblasts and determined that knockout of the
      miR-302/367 cluster completely blocked induced pluripotent stem cell (iPSC)
      generation. Together, our results demonstrate that TALE-based transcriptional
      repressor and TALENs are two promising approaches for loss-of-function studies of
      microRNA clusters in somatic cells and pluripotent stem cells. 

PMID- 24319659
TI  - Genetic correction of tauopathy phenotypes in neurons derived from human induced
      pluripotent stem cells.
AB  - Tauopathies represent a group of neurodegenerative disorders characterized by the
      accumulation of pathological TAU protein in brains. We report a human neuronal
      model of tauopathy derived from induced pluripotent stem cells (iPSCs) carrying a
      TAU-A152T mutation. Using zinc-finger nuclease-mediated gene editing, we
      generated two isogenic iPSC lines: one with the mutation corrected, and another
      with the homozygous mutation engineered. The A152T mutation increased TAU
      fragmentation and phosphorylation, leading to neurodegeneration and especially
      axonal degeneration. These cellular phenotypes were consistent with those
      observed in a patient with TAU-A152T. Upon mutation correction, normal neuronal
      and axonal morphologies were restored, accompanied by decreases in TAU
      fragmentation and phosphorylation, whereas the severity of tauopathy was
      intensified in neurons with the homozygous mutation. These isogenic TAU-iPSC
      lines represent a critical advancement toward the accurate modeling and
      mechanistic study of tauopathies with human neurons and will be invaluable for
      drug-screening efforts and future cell-based therapies. 

PMID- 24319660
TI  - Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state.
AB  - Direct reprogramming of adult somatic cells into alternative cell types has been
      shown for several lineages. We previously showed that GATA4, MEF2C, and TBX5
      (GMT) directly reprogrammed nonmyocyte mouse heart cells into induced
      cardiomyocyte-like cells (iCMs) in vitro and in vivo. However, GMT alone appears
      insufficient in human fibroblasts, at least in vitro. Here, we show that GMT plus
      ESRRG and MESP1 induced global cardiac gene-expression and phenotypic shifts in
      human fibroblasts derived from embryonic stem cells, fetal heart, and neonatal
      skin. Adding Myocardin and ZFPM2 enhanced reprogramming, including sarcomere
      formation, calcium transients, and action potentials, although the efficiency
      remained low. Human iCM reprogramming was epigenetically stable. Furthermore, we
      found that transforming growth factor beta signaling was important for, and
      improved the efficiency of, human iCM reprogramming. These findings demonstrate
      that human fibroblasts can be directly reprogrammed toward the cardiac lineage,
      and lay the foundation for future refinements in vitro and in vivo. 

PMID- 24319661
TI  - TBX3 Directs Cell-Fate Decision toward Mesendoderm.
AB  - Cell-fate decisions and pluripotency are dependent on networks of key
      transcriptional regulators. Recent reports demonstrated additional functions of
      pluripotency-associated factors during early lineage commitment. The T-box
      transcription factor TBX3 has been implicated in regulating embryonic stem cell
      self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed
      during specification of the mesendoderm lineages in differentiating embryonic
      stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo.
      Forced TBX3 expression in ESCs promotes mesendoderm specification by directly
      activating key lineage specification factors and indirectly by enhancing
      paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus
      underline its requirement for mesendoderm lineage commitment. Moreover, we
      uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus
      gastrulation. Taken together, we define further facets of TBX3 actions and map
      TBX3 as an upstream regulator of the mesendoderm transcriptional program during
      gastrulation.

PMID- 24319662
TI  - Transcriptome analysis identifies regulators of hematopoietic stem and progenitor
      cells.
AB  - Hematopoietic stem cells (HSCs) maintain blood homeostasis and are the functional
      units of bone marrow transplantation. To improve the molecular understanding of
      HSCs and their proximal progenitors, we performed transcriptome analysis within
      the context of the ImmGen Consortium data set. Gene sets that define steady-state
      and mobilized HSCs, as well as hematopoietic stem and progenitor cells (HSPCs),
      were determined. Genes involved in transcriptional regulation, including a group
      of putative transcriptional repressors, were identified in multipotent
      progenitors and HSCs. Proximal promoter analyses combined with ImmGen module
      analysis identified candidate regulators of HSCs. Enforced expression of one
      predicted regulator, Hlf, in diverse HSPC subsets led to extensive self-renewal
      activity ex vivo. These analyses reveal unique insights into the mechanisms that
      control the core properties of HSPCs. 

PMID- 24319663
TI  - iPSC-Based cell therapy: an important step forward.
AB  - Morizane et al. (2013) show that donor-matched differentiated derivatives of
      induced pluripotent stem cells (iPSC) do not cause an immune response after
      transplantation, whereas transplantation of HLA-mismatched iPSC derivatives to
      the same site clearly does. The importance of these results is discussed in this
      commentary as we assess how best to move forward with iPSC-based cell therapy. 

PMID- 24319664
TI  - Direct comparison of autologous and allogeneic transplantation of iPSC-derived
      neural cells in the brain of a non-human primate.
AB  - Induced pluripotent stem cells (iPSCs) provide the potential for autologous
      transplantation using cells derived from a patient's own cells. However, the
      immunogenicity of iPSCs or their derivatives has been a matter of controversy,
      and up to now there has been no direct comparison of autologous and allogeneic
      transplantation in the brains of humans or nonhuman primates. Here, using
      nonhuman primates, we found that the autologous transplantation of iPSC-derived
      neurons elicited only a minimal immune response in the brain. In contrast, the
      allografts caused an acquired immune response with the activation of microglia
      (IBA-1(+)/MHC class II(+)) and the infiltration of leukocytes (CD45(+)/CD3(+)).
      Consequently, a higher number of dopaminergic neurons survived in the autografts.
      Our results suggest that the autologous transplantation of iPSC-derived neural
      cells is advantageous for minimizing the immune response in the brain compared
      with allogeneic grafts. 

PMID- 24319665
TI  - Generation of multipotent foregut stem cells from human pluripotent stem cells.
AB  - Human pluripotent stem cells (hPSCs) could provide an infinite source of
      clinically relevant cells with potential applications in regenerative medicine.
      However, hPSC lines vary in their capacity to generate specialized cells, and the
      development of universal protocols for the production of tissue-specific cells
      remains a major challenge. Here, we have addressed this limitation for the
      endodermal lineage by developing a defined culture system to expand and
      differentiate human foregut stem cells (hFSCs) derived from hPSCs. hFSCs can self
      renew while maintaining their capacity to differentiate into pancreatic and
      hepatic cells. Furthermore, near-homogenous populations of hFSCs can be obtained
      from hPSC lines which are normally refractory to endodermal differentiation.
      Therefore, hFSCs provide a unique approach to bypass variability between
      pluripotent lines in order to obtain a sustainable source of multipotent endoderm
      stem cells for basic studies and to produce a diversity of endodermal derivatives
      with a clinical value. 

PMID- 24319666
TI  - L-Proline induces a mesenchymal-like invasive program in embryonic stem cells by
      remodeling H3K9 and H3K36 methylation.
AB  - Metabolites are emerging as key mediators of crosstalk between metabolic flux,
      cellular signaling, and epigenetic regulation of cell fate. We found that the
      nonessential amino acid L-proline (L-Pro) acts as a signaling molecule that
      promotes the conversion of embryonic stem cells into mesenchymal-like, spindle
      shaped, highly motile, invasive pluripotent stem cells. This embryonic-stem-cell
      to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling
      of the H3K9 and H3K36 methylation status. Consistently, L-Pro-induced esMT is
      fully reversible either after L-Pro withdrawal or by addition of ascorbic acid
      (vitamin C), which in turn reduces H3K9 and H3K36 methylation, promoting a
      mesenchymal-like-to-embryonic-stem-cell transition (MesT). These findings suggest
      that L-Pro, which is produced by proteolytic remodeling of the extracellular
      matrix, may act as a microenvironmental cue to control stem cell behavior. 

PMID- 24319667
TI  - Long-term self-renewal of human ES/iPS-derived hepatoblast-like cells on human
      laminin 111-coated dishes.
AB  - The establishment of self-renewing hepatoblast-like cells (HBCs) from human
      pluripotent stem cells (PSCs) would realize a stable supply of hepatocyte-like
      cells for medical applications. However, the functional characterization of human
      PSC-derived HBCs was not enough. To purify and expand human PSC-derived HBCs,
      human PSC-derived HBCs were cultured on dishes coated with various types of human
      recombinant laminins (LN). Human PSC-derived HBCs attached to human laminin-111
      (LN111)-coated dish via integrin alpha 6 and beta 1 and were purified and
      expanded by culturing on the LN111-coated dish, but not by culturing on dishes
      coated with other laminin isoforms. By culturing on the LN111-coated dish, human
      PSC-derived HBCs were maintained for more than 3 months and had the ability to
      differentiate into both hepatocyte-like cells and cholangiocyte-like cells. These
      expandable human PSC-derived HBCs would be manageable tools for drug screening,
      experimental platforms to elucidate mechanisms of hepatoblasts, and cell sources
      for hepatic regenerative therapy. 

PMID- 24319668
TI  - Analysis of induced pluripotent stem cells from a BRCA1 mutant family.
AB  - Understanding BRCA1 mutant cancers is hampered by difficulties in obtaining
      primary cells from patients. We therefore generated and characterized 24 induced
      pluripotent stem cell (iPSC) lines from fibroblasts of eight individuals from a
      BRCA1 5382insC mutant family. All BRCA1 5382insC heterozygous fibroblasts, iPSCs,
      and teratomas maintained equivalent expression of both wild-type and mutant BRCA1
      transcripts. Although no difference in differentiation capacity was observed
      between BRCA1 wild-type and mutant iPSCs, there was elevated protein kinase C
      theta (PKC-theta) in BRCA1 mutant iPSCs. Cancer cell lines with BRCA1 mutations
      and hormone-receptor-negative breast cancers also displayed elevated PKC-theta.
      Genome sequencing of the 24 iPSC lines showed a similar frequency of
      reprogramming-associated de novo mutations in BRCA1 mutant and wild-type iPSCs.
      These data indicate that iPSC lines can be derived from BRCA1 mutant fibroblasts
      to study the effects of the mutation on gene expression and genome stability. 

PMID- 24319669
TI  - Fast quantitative real-time PCR-based screening for common chromosomal
      aneuploidies in mouse embryonic stem cells.
AB  - Chromosomal integrity has been known for many years to affect the ability of
      mouse embryonic stem cells (mESCs) to contribute to the germline of chimeric
      mice. Abnormal chromosomes are generally detected by standard cytogenetic
      karyotyping. However, this method is expensive, time consuming, and often omitted
      prior to blastocyst injection, consequently reducing the frequency of mESC
      derived offspring. Here, we show a fast, accurate, and inexpensive screen for
      identifying the two most common aneuploidies (Trisomy 8 and loss of chromosome Y)
      in genetically manipulated mESCs using quantitative real-time PCR (qPCR).
      Screening against these two aneuploidies significantly increases the fraction of
      normal mESC clones. Our method is extremely sensitive and can detect as low as
      10% aneuploidy among a large population of mESCs. It greatly expedites the
      generation of mutant mice and provides a quick tool for assessing the aneuploidy
      percentages of any mESC line. 

PMID- 24319671
TI  - Differences in Risk Aversion between Young and Older Adults.
AB  - Research on decision-making strategies among younger and older adults suggests
      that older adults may be more risk averse than younger people in the case of
      potential losses. These results mostly come from experimental studies involving
      gambling paradigms. Since these paradigms involve substantial demands on memory
      and learning, differences in risk aversion or other features of decision-making
      attributed to age may in fact reflect age-related declines in cognitive
      abilities. In the current study, older and younger adults completed a simpler,
      paired lottery choice task used in the experimental economics literature to
      elicit risk aversion. A similar approach was used to elicit participants'
      discount rates. The older adult group was more risk averse than younger adults (p
      < .05) and also had a higher discount rate (15.6-21.0% vs. 10.3-15.5%, p < .01),
      indicating lower expected utility from future income. Risk aversion and implied
      discount rates were weakly correlated. It may be valuable to investigate
      developmental changes in neural correlates of decision-making across the
      lifespan.

PMID- 24319670
TI  - Identifying division symmetry of mouse embryonic stem cells: negative impact of
      DNA methyltransferases on symmetric self-renewal.
AB  - Cell division is a process by which a mother cell divides into genetically
      identical sister cells, although sister cells often display considerable
      diversity. In this report, over 350 sister embryonic stem cells (ESCs) were
      isolated through a microdissection method, and then expression levels of 48 key
      genes were examined for each sister cell. Our system revealed considerable
      diversities between sister ESCs at both pluripotent and differentiated states,
      whereas the similarity between sister ESCs was significantly elevated in a 2i
      (MEK and GSK3b inhibitors) condition, which is believed to mimic the ground state
      of pluripotency. DNA methyltransferase 3a/3b were downregulated in 2i-grown ESCs,
      and the loss of DNA methyltransferases was sufficient to generate nearly
      identical sister cells. These results suggest that DNA methylation is a major
      cause of the diversity between sister cells at the pluripotent states, and thus
      demethylation per se plays an important role in promoting ESC's self-renewal. 

PMID- 24319672
TI  - Efficacy of Long-term Effect and Repeat Intraarticular Botulinum toxin in
      Patients with Painful Total Joint Arthroplasty: A Retrospective Study.
AB  - OBJECTIVE: Based on recent success of intra-articular (IA) Botulinum neurotoxin
      type A (BoNT/A; OnabotulinumtoxinA) in patients with osteoarthritis, we examined
      if repeat IA-BoNT/A is an effective antinociceptive in patients with refractory
      arthroplasty pain. METHODS: 11 patients with refractory chronic arthroplasty
      joint pain without any evidence of infection or prosthesis loosening were
      referred by orthopedic surgeons. After discussion of off-label use, each patient
      underwent IA injection of BoNT/A, repeated based on return of pain on numeric
      rating scale (NRS) and functional limitation on composite validated scales,
      Western Ontario McMaster Osteoarthritis index (WOMAC) or Shoulder Pain and
      Disability (SPADI). RESULTS: 11 patients (10 men, 1 woman) with 14 painful
      arthroplasty joints (3 bilateral; 12 knee and 2 shoulder) underwent >=1 IA-BoNT/A
      injections (8 joints injected once, one joint injected twice only, five joints
      injected thrice) with doses ranging 100-300 units. Mean age was 68 years
      (standard deviation, 12) and follow-up ranged 1-28 months. Clinically meaningful
      reduction of 2-units in pain severity and really meaningful reduction in pain
      severity (50% reduction) were reported by 6/11 patients (6/13 joints) and 3/11
      patients (3/13 joints), respectively, 1 month after the first IA-BoNT/A (100
      units each). Significant improvements were noted in composite functional scales
      (WOMAC/SPADI). Pain relief was sustained at 3-4 month follow-up and was
      reproducible in those who received repeat injections. No significant adverse
      events were seen in any patients. CONCLUSIONS: A single intra-articular injection
      of BoNT/A improved pain and function in patients with chronic, refractory painful
      knee or shoulder arthroplasty, which sustained with repeat injections. Patients
      who were refractory to the first injection, did not respond to subsequent
      injections of higher dose of IA-BoNT/A.

PMID- 24319673
TI  - Interaction of streptococcal plasminogen binding proteins with the host
      fibrinolytic system.
AB  - The ability to take advantage of plasminogen and its activated form plasmin is a
      common mechanism used by commensal as well as pathogenic bacteria in interaction
      with their respective host. Hence, a huge variety of plasminogen binding proteins
      and activation mechanisms exist. This review solely focuses on the genus
      Streptococcus and, in particular, on the so-called non-activating plasminogen
      binding proteins. Based on structural and functional differences, as well as on
      their mode of surface linkaging, three groups can be assigned: M-(like) proteins,
      surface displayed cytoplasmatic proteins with enzymatic activities ("moonlighting
      proteins") and other surface proteins. Here, the plasminogen binding sites and
      the interaction mechanisms are compared. Recent findings on the functional
      consequences of these interactions on tissue degradation and immune evasion are
      summarized. 

PMID- 24319674
TI  - XRCC7 rs#7003908 Polymorphism and Helicobacter pylori Infection-Related Gastric
      Antrum Adenocarcinoma.
AB  - The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA
      repair that protects against genetic instability and carcinogenesis. To determine
      whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter
      pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we
      conducted a hospital-based case-control study, including 642 patients with
      pathologically confirmed GAA and 927 individually matched controls without any
      evidence of tumours or precancerous lesions, among Guangxi population. Increased
      risks of GAA were observed for individuals with cagA positive (odds ratio (OR)
      6.38; 95% confidence interval (CI) 5.03-8.09). We also found that these
      individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG)
      featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the
      homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did
      appear to differ more significantly among individuals featuring cagA-positive
      status, whose adjusted ORs (95% CIs) were 15.74 (10.89-22.77) for XRCC7-TG and
      38.49 (22.82-64.93) for XRCC7-GG, respectively. Additionally, this polymorphism
      multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC
      risk (ORinteraction = 1.49). These results suggest that XRCC7P may be associated
      with the risk of Guangxiese GAA related to cagA. 

PMID- 24319675
TI  - Slack, Slick and Sodium-Activated Potassium Channels.
AB  - The Slack and Slick genes encode potassium channels that are very widely
      expressed in the central nervous system. These channels are activated by
      elevations in intracellular sodium, such as those that occur during trains of one
      or more action potentials, or following activation of non-selective cationic
      neurotransmitter receptors such as AMPA receptors. This review covers the
      cellular and molecular properties of Slack and Slick channels and compares them
      with findings on the properties of sodium-activated potassium currents (termed
      KNa currents) in native neurons. Human mutations in Slack channels produce
      extremely severe defects in learning and development, suggesting that KNa
      channels play a central role in neuronal plasticity and intellectual function.

PMID- 24319676
TI  - Exogenous nucleotides antagonize the developmental toxicity of ethanol in vitro.
AB  - The objective of this study was to assess whether nucleotides supplementation in
      vitro could suppress ethanol-induced developmental toxicity in mouse. The models
      of whole embryo culture (WEC) and midbrain (MB) cell micromass culture were used
      in this study. In WEC system, exposure to 4.0 mg/mL ethanol for 48 h yielded
      various developmental malformations of the mice embryos. Nucleotides
      supplementation (0.16, 0.80, 4.00, 20.00, and 100.00 mg/L) improved the growth
      parameters to some extent, and the protective effects peaked at 4.00 mg/L. In MB
      cell micromass culture system, exposure to 4.0 mg/mL ethanol for 5 days resulted
      in suppression of proliferation and differentiation. Supplementation of
      nucleotides (0.16, 0.80, 4.00, 20.00, and 100.00 mg/L) showed some protective
      effects, which peaked at 4.00 mg/L, too. The present research indicated that
      nucleotides supplementation might be of some benefit in the prevention of ethanol
      induced birth defects; however, appropriate dosage requires attention.

PMID- 24319677
TI  - Ocular dominance and visual function testing.
AB  - PURPOSE: To show the distribution of ocular dominance as measured with sensory
      and eye sighting methods and its potential relationship with high and low
      contrast LogMAR visual acuity in presbyopic subjects. METHOD: Forty-four
      presbyopes (48.5 +/- 3.5 years) participated in this study. Ocular dominance was
      determined by eye sighting (hole-in-card) and sensorial (+1.50 D lens induced
      blur) methods. According to the dominance detected with each method (RE: right
      eye or LE: left eye), patients were classified in dominance type 1 (RE/RE), type
      2 (RE/LE), type 3 (LE/RE) and type 4 (LE/LE). RESULTS: Baseline refractive error
      (MSE) was RE:-0.36 +/- 1.67 D and LE:-0.35 +/- 1.85 D (P = 0.930). RE was the
      dominant eye in 61.4% and 70.5% of times as obtained from sensorial and sighting
      methods, respectively. Most frequent dominance was of type 1 (52.3%), in this
      case the RE showed statistically significant better distance low contrast LogMAR
      VA (0.04 LogMAR units) compared to the LE (P < 0.05). CONCLUSIONS: The dominance
      was more frequent in RE in this sample. The eye sighting and sensorial methods to
      define ocular dominance agreed in more than half of cases. Amount of MSE was not
      significantly different between dominant and non-dominant eye. But in case of
      right dominance, the RE presented better distance low contrast VA compared to the
      LE.

PMID- 24319678
TI  - Mesenchymal stem cell-like cells derived from mouse induced pluripotent stem
      cells ameliorate diabetic polyneuropathy in mice.
AB  - BACKGROUND: Although pathological involvements of diabetic polyneuropathy (DPN)
      have been reported, no dependable treatment of DPN has been achieved. Recent
      studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we
      demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC
      like cells and investigate the therapeutic potential of the MSC-like cell
      transplantation on DPN. RESEARCH DESIGN AND METHODS: For induction into MSC-like
      cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by
      adherent culture for 4 months. The MSC-like cells, characterized with flow
      cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin
      diabetic mice. Three weeks after the transplantation, neurophysiological
      functions were evaluated. RESULTS: The MSC-like cells expressed MSC markers and
      angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb
      muscles and peripheral nerves, and some transplanted cells expressed S100 beta in
      the nerves. Impairments of current perception thresholds, nerve conduction
      velocities, and plantar skin blood flow in the diabetic mice were ameliorated in
      limbs with the transplanted cells. The capillary number-to-muscle fiber ratios
      were increased in transplanted hindlimbs of diabetic mice. CONCLUSIONS: These
      results suggest that MSC-like cell transplantation might have therapeutic effects
      on DPN through secreting angiogenic/neurotrophic factors and differentiation to
      Schwann cell-like cells.

PMID- 24319679
TI  - Biohydrogen production and kinetic modeling using sediment microorganisms of
      Pichavaram mangroves, India.
AB  - Mangrove sediments host rich assemblages of microorganisms, predominantly mixed
      bacterial cultures, which can be efficiently used for biohydrogen production
      through anaerobic dark fermentation. The influence of process parameters such as
      effect of initial glucose concentration, initial medium pH, and trace metal
      (Fe(2+)) concentration was investigated in this study. A maximum hydrogen yield
      of 2.34, 2.3, and 2.6 mol H2 mol(-1) glucose, respectively, was obtained under
      the following set of optimal conditions: initial substrate concentration-10,000
      mg L(-1), initial pH-6.0, and ferrous sulphate concentration-100 mg L(-1),
      respectively. The addition of trace metal to the medium (100 mg L(-1) FeSO4
      .7H2O) enhanced the biohydrogen yield from 2.3 mol H2 mol(-1) glucose to 2.6 mol
      H2 mol(-1) glucose. Furthermore, the experimental data was subjected to kinetic
      analysis and the kinetic constants were estimated with the help of well-known
      kinetic models available in the literature, namely, Monod model, logistic model
      and Luedeking-Piret model. The model fitting was found to be in good agreement
      with the experimental observations, for all the models, with regression
      coefficient values >0.92.

PMID- 24319680
TI  - Occupational allergic diseases in kitchen and health care workers: an
      underestimated health issue.
AB  - OBJECTIVE: This study evaluated the frequencies of allergic symptoms and rate of
      upper respiratory infections during the past year in the general population,
      kitchen workers (KW) and health care workers (HCW). METHODS: The European
      Community Respiratory Health Survey (ECRHS) was used to inquire retrospectively
      about asthma and asthma-like symptoms and the number of treatments required for
      previous upper respiratory tract infections (URTI: acute pharyngitis, acute
      sinusitis, etc.) during the past year for health care workers, kitchen workers,
      and members of the general population. Adjusted odds ratios by gender, age, and
      smoking status were calculated. RESULTS: 579 subjects (186 from the general
      population, 205 KW, and 188 HCW; 263 females, 316 males) participated in the
      study. Noninfectious (allergic) rhinitis was significantly higher in the HCW and
      KW groups than in the general population (P < 0.001). Cumulative asthma was
      significantly higher only in the HCW group (P < 0.05). In addition, the HCW and
      KW groups had significantly higher risks of >=2/year URTI (OR: 1.59, 95% CI: 1.07
      2.38 versus OR: 1.57, 95% CI: 1.05-2.38) than the general population. CONCLUSION:
      Occupational allergic respiratory diseases are an important and growing health
      issue. Health care providers should become familiar with workplace environments
      and environmental causes of occupational rhinitis and asthma.

PMID- 24319681
TI  - Changes in frequency-doubling perimetry in patients with type I diabetes prior to
      retinopathy.
AB  - PURPOSE: To evaluate the ability of frequency-doubling technology (FDT) perimetry
      in detecting visual field defects in young adults with type I diabetes prior to
      retinopathy or with minor retinovascular changes. METHODS: This comparative cross
      sectional study included 30 healthy subjects and 73 age-matched patients with
      type I diabetes mellitus. All subjects underwent a full ocular examination
      including an FDT with the threshold C-20-5 strategy. Only one eye per subject was
      randomly included in the statistical analysis. FDT results and time to perform
      the test were compared between the groups. RESULTS: The mean age was 27.1 years
      in the control group and 26.6 years in the diabetic group (P = 0.875). The mean
      period from the onset of diabetes was 12.6 +/- 6.7 years, while minimal
      retinovascular changes were observed in 18 eyes. Mean deviation of FDT did not
      differ between the groups. Although global indices of FDT were within normal
      limits, pattern standard deviation of FDT was higher in the diabetic group (P =
      0.035). The area under the receiver operating characteristic curve was 0.647 for
      pattern standard deviation of FDT (standard error = 0.052; P = 0.017).
      CONCLUSION: FDT can detect retinal dysfunctions in diabetic patients prior to the
      onset of significant vascular complications.

PMID- 24319682
TI  - Growth arrest on inhibition of nonsense-mediated decay is mediated by noncoding
      RNA GAS5.
AB  - Nonsense-mediated decay is a key RNA surveillance mechanism responsible for the
      rapid degradation of mRNAs containing premature termination codons and hence
      prevents the synthesis of truncated proteins. More recently, it has been shown
      that nonsense-mediated decay also has broader significance in controlling the
      expression of a significant proportion of the transcriptome. The importance of
      this mechanism to the mammalian cell is demonstrated by the observation that its
      inhibition causes growth arrest. The noncoding RNA growth arrest specific
      transcript 5 (GAS5) has recently been shown to play a key role in growth arrest
      induced by several mechanisms, including serum withdrawal and treatment with the
      mTOR inhibitor rapamycin. Here we show that inhibition of nonsense-mediated decay
      in several human lymphocyte cell lines causes growth arrest, and siRNA-mediated
      downregulation of GAS5 in these cells significantly alleviates the inhibitory
      effects observed. These observations hold true for inhibition of nonsense
      mediated decay both through RNA interference and through pharmacological
      inhibition by aminoglycoside antibiotics gentamycin and G418. These studies have
      important implications for ototoxicity and nephrotoxicity caused by gentamycin
      and for the proposed use of NMD inhibition in treating genetic disease. This
      report further demonstrates the critical role played by GAS5 in the growth arrest
      of mammalian cells. 

PMID- 24319683
TI  - Estrogen signaling through estrogen receptor beta and G-protein-coupled estrogen
      receptor 1 in human cerebral vascular endothelial cells: implications for
      cerebral aneurysms.
AB  - Little is known about estrogen receptors and their signaling mechanisms in human
      cerebral vascular endothelial cells, which is important for understanding
      cerebral aneurysm pathogenesis in menopausal and postmenopausal women. Estrogen
      receptor beta (ERbeta) and G-protein-coupled receptor 1 (GPER1) were
      immunocytochemically identified in human cerebral vascular endothelial cells
      (HCVECs). ERbeta was mainly located at the nuclei of the cells while GPER1 was
      located at the plasma membrane. Interaction events between 17beta-estradiol and
      ERbeta or GPER1 in HCVECs were evaluated by in situ proximity ligation assay. The
      number of interaction events between 17beta-estradiol and ERbeta was positively
      correlated with 17beta-estradiol concentrations (r = 0.9614, P < 0.01). The
      interaction events between 17beta-estradiol and GPER1 were dose responsive. Our
      data support HCVECs to serve as a suitable cellular model for studying cerebral
      aneurysm pathogenesis in menopausal and postmenopausal women. Subtypes of
      estrogen receptors and their signaling mechanisms identified in HCVECs could be
      applicable for developing estrogen-like compounds to specifically bind to a
      subtype of estrogen receptors with greater specific action on the cerebral
      arteries, without the estrogen-dependent side effects on the reproductive organs,
      to prevent cerebral aneurysm formation in menopausal and postmenopausal woman.

PMID- 24319684
TI  - Magnetic retraction of bowel by intraluminal injectable cyanoacrylate-based
      magnetic glue.
AB  - Magnetic retraction offers advantages over physical retraction by graspers
      because of reduced tissue trauma. The objectives of this study are to investigate
      a novel method of magnetisation of bowel segments by intraluminal injection of
      magnetic glue and to demonstrate the feasibility of magnetic retraction of bowel
      with sufficient force during minimal access surgery. Following an initial
      materials characterisation study, selected microparticles of stainless steel
      (SS410- MU Ps) were mixed with chosen cyanoacrylate glue (Loctite 4014). During
      intraluminal injection of the magnetic glue using ex vivo porcine colonic
      segments, a magnetic probe placed at the injected site ensured that the SS410
      MUPs aggregated during glue polymerisation to form an intraluminal mucosally
      adherent coagulum. The magnetised colonic segments were retracted by magnetic
      probes (5 and 10 mm) placed external to the bowel wall. A tensiometer was used to
      record the retraction force. With an injected volume of 2 mL in a particle
      concentration of 1 g/mL, this technique produced maximal magnetic retraction
      forces of 2.24 +/- 0.23 N and 5.11 +/- 0.34 N (n = 20), with use of 5 and 10 mm
      probes, respectively. The results indicate that the formation of an intraluminal
      coagulum based on SS410- MUPs and Loctite 4014 produces sufficient magnetic
      retraction for bowel retraction.

PMID- 24319685
TI  - Comparison of new technology integrated and nonintegrated arterial filters used
      in cardiopulmonary bypass surgery: a randomized, prospective, and single blind
      study.
AB  - BACKGROUND: Innovative cardiopulmonary bypass (CPB) settings have been developed
      in order to integrate the concepts of "surface-coating," "blood-filtration," and
      "miniaturization." OBJECTIVES: To compare integrated and nonintegrated arterial
      line filters in terms of peri- and postoperative clinical variables, inflammatory
      response, and transfusion needs. MATERIAL AND METHODS: Thirty-six patients who
      underwent coronary bypass surgery were randomized into integrated (Group In) and
      nonintegrated arterial line filter (Group NIn) groups. Arterial blood samples for
      the assessments of complete hemogram, biochemical screening, interleukin-6,
      interleukin-2R, and C-reactive protein were analyzed before and after surgery.
      Need for postoperative dialysis, inotropic therapy and transfusion, in addition
      to extubation time, total amount of drainage (mL), length of intensive care unit,
      and hospital stay, and mortality rates was also recorded for each patient.
      RESULTS: Prime volume was significantly higher and mean intraoperative hematocrit
      value was lower in Group NIn, but need for erythrocyte transfusion was
      significantly higher in Group NIn. C-reactive protein values did not differ
      significantly except for postoperative second day's results, which were found
      significantly lower in Group In than in Group NIn. CONCLUSION: Intraoperative
      hematocrit levels were higher and need for postoperative erythrocyte transfusion
      was decreased in Group In.

PMID- 24319686
TI  - Long-term effects of nilvadipine against progression of the central visual field
      defect in retinitis pigmentosa: an extended study.
AB  - PURPOSE: To assess the long-term effects of nilvadipine on the progression of
      central visual field defect in retinitis pigmentosa (RP). METHODS: Patients with
      RP were randomly divided into a treated group receiving oral nilvadipine and a
      control group. Progression of RP was evaluated with MD slope and the average
      sensitivity of the central 2 degrees  (DeltaCENT4). RESULTS: The mean MD slopes
      were -0.55/-0.39 (right/left eyes, n = 19) dB/year in the treated group and 
      1.37/-1.15 (right/left eyes, n = 22) dB/year in the control group (P =
      0.016/0.050, resp.). In both eyes, however, no statistical difference was
      observed between the two groups for the DeltaCENT4 values. CONCLUSION: Although
      we confirmed that nilvadipine significantly retarded the progression of the
      average of MD value defects in the central 10 degrees , it was not specific for
      the central 2 degrees  of the visual field in RP.

PMID- 24319687
TI  - CD59 underlines the antiatherosclerotic effects of C-phycocyanin on mice.
AB  - The effects of C-phycocyanin (C-PC) on atherosclerosis and the regulatory effects
      of CD59 gene on anti-atherosclerotic roles of C-PC were investigated.
      Apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into four
      groups: control group, C-PC treatment group, CD59 transfection group and C
      PC+CD59 synergy group. The mice were fed with high-fat-diet and treated with drug
      intervention at the same time. Results showed the atherosclerotic mouse model was
      successfully established. CD59 was over-expressed in blood and tissue cells.
      Single CD59 or C-PC could reduce blood lipid levels and promote the expression of
      anti-apoptotic Bcl-2 but inhibit pro-apoptotic Fas proteins in endothelial cells.
      The expression levels of cell cycle protein D1 (Cyclin D1) and mRNA levels of
      cyclin dependent protein kinase 4 (CDK4) in smooth muscle cells were restrained
      by CD59 and C-PC. CD59 or C-PC alone could inhibit the formation of
      atherosclerotic plaque by suppressing MMP-2 protein expression. In addition, C-PC
      could promote CD59 expression. So both CD59 and C-PC could inhibit the progress
      of atherosclerosis, and the anti-atherosclerotic effects of C-PC might be
      fulfilled by promoting CD59 expression, preventing smooth muscle cell
      proliferation and the apoptosis of endothelial cells, reducing blood fat levels,
      and at last inhibiting the development of atherosclerosis. 

PMID- 24319688
TI  - Therapies for neovascular age-related macular degeneration: current approaches
      and pharmacologic agents in development.
AB  - As one of the leading causes of blindness, age-related macular degeneration (AMD)
      has remained at the epicenter of clinical research in ophthalmology. During the
      past decade, focus of researchers has ranged from understanding the role of
      vascular endothelial growth factor (VEGF) in the angiogenic cascades to
      developing new therapies for retinal vascular diseases. Anti-VEGF agents such as
      ranibizumab and aflibercept are becoming increasingly well-established therapies
      and have replaced earlier approaches such as laser photocoagulation or
      photodynamic therapy. Many other new therapeutic agents, which are in the early
      phase clinical trials, have shown promising results. The purpose of this paper is
      to briefly review the available treatment modalities for neovascular AMD and then
      focus on promising new therapies that are currently in various stages of
      development. 

PMID- 24319690
TI  - Role of NADPH oxidase-mediated reactive oxygen species in podocyte injury.
AB  - Proteinuria is an independent risk factor for end-stage renal disease (ESRD)
      (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury
      and implications for potential treatment strategies in proteinuric kidney
      diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals
      which are closely associated with the development and progression of glomerular
      sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS
      production and prominently expressed in podocytes (Zhang et al., 2010). In the
      last decade, it has become evident that NADPH oxidase-derived ROS overproduction
      is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system
      activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition
      (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review
      focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under
      different pathophysiological conditions. In addition, we also reviewed the
      therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte
      injury. 

PMID- 24319689
TI  - The roles of genetic polymorphisms and human immunodeficiency virus infection in
      lipid metabolism.
AB  - Dyslipidemia has been frequently observed among individuals infected with human
      immunodeficiency virus type 1 (HIV-1), and factors related to HIV-1, the host,
      and antiretroviral therapy (ART) are involved in this phenomenon. This study
      reviews the roles of genetic polymorphisms, HIV-1 infection, and highly active
      antiretroviral therapy (HAART) in lipid metabolism. Lipid abnormalities can vary
      according to the HAART regimen, such as those with protease inhibitors (PIs).
      However, genetic factors may also be involved in dyslipidemia because not all
      patients receiving the same HAART regimen and with comparable demographic,
      virological, and immunological characteristics develop variations in the lipid
      profile. Polymorphisms in a large number of genes are involved in the synthesis
      of structural proteins, and enzymes related to lipid metabolism account for
      variations in the lipid profile of each individual. As some genetic polymorphisms
      may cause dyslipidemia, these allele variants should be investigated in HIV-1
      infected patients to identify individuals with an increased risk of developing
      dyslipidemia during treatment with HAART, particularly during therapy with PIs.
      This knowledge may guide individualized treatment decisions and lead to the
      development of new therapeutic targets for the treatment of dyslipidemia in these
      patients. 

PMID- 24319692
TI  - QPLOT: a quality assessment tool for next generation sequencing data.
AB  - BACKGROUND: Next generation sequencing (NGS) is being widely used to identify
      genetic variants associated with human disease. Although the approach is cost
      effective, the underlying data is susceptible to many types of error.
      Importantly, since NGS technologies and protocols are rapidly evolving, with
      constantly changing steps ranging from sample preparation to data processing
      software updates, it is important to enable researchers to routinely assess the
      quality of sequencing and alignment data prior to downstream analyses. RESULTS:
      Here we describe QPLOT, an automated tool that can facilitate the quality
      assessment of sequencing run performance. Taking standard sequence alignments as
      input, QPLOT generates a series of diagnostic metrics summarizing run quality and
      produces convenient graphical summaries for these metrics. QPLOT is
      computationally efficient, generates webpages for interactive exploration of
      detailed results, and can handle the joint output of many sequencing runs.
      CONCLUSION: QPLOT is an automated tool that facilitates assessment of sequence
      run quality. We routinely apply QPLOT to ensure quick detection of diagnostic of
      sequencing run problems. We hope that QPLOT will be useful to the community as
      well.

PMID- 24319691
TI  - Changes in Otx2 and parvalbumin immunoreactivity in the superior colliculus in
      the platelet-derived growth factor receptor-beta knockout mice.
AB  - The superior colliculus (SC), a relay nucleus in the subcortical visual pathways,
      is implicated in socioemotional behaviors. Homeoprotein Otx2 and beta subunit of
      receptors of platelet-derived growth factor (PDGFR- beta ) have been suggested to
      play an important role in development of the visual system and development and
      maturation of GABAergic neurons. Although PDGFR- beta -knockout (KO) mice
      displayed socio-emotional deficits associated with parvalbumin (PV
      )immunoreactive (IR) neurons, their anatomical bases in the SC were unknown. In
      the present study, Otx2 and PV-immunolabeling in the adult mouse SC were
      investigated in the PDGFR- beta KO mice. Although there were no differences in
      distribution patterns of Otx2 and PV-IR cells between the wild type and PDGFR-
      beta KO mice, the mean numbers of both of the Otx2- and PV-IR cells were
      significantly reduced in the PDGFR- beta KO mice. Furthermore, average diameters
      of Otx2- and PV-IR cells were significantly reduced in the PDGFR- beta KO mice.
      These findings suggest that PDGFR- beta plays a critical role in the functional
      development of the SC through its effects on Otx2- and PV-IR cells, provided
      specific roles of Otx2 protein and PV-IR cells in the development of SC neurons
      and visual information processing, respectively. 

PMID- 24319693
TI  - Incidence of Japanese encephalitis among acute encephalitis syndrome cases in
      West Bengal, India.
AB  - BACKGROUND AND OBJECTIVES: Japanese encephalitis (JE) is the most important cause
      of acute and epidemic viral encephalitis. Every year sporadic JE cases are
      reported from the various districts of West Bengal, indicating its endemicity in
      this state. JE vaccination programme has been undertaken by the State Health
      Department of West Bengal. This study was aimed at seeing the present scenario of
      JE among acute encephalitis syndrome (AES) cases in West Bengal. MATERIALS AND
      METHODS: Blood and/or CSF samples were referred from suspected AES cases to the
      referral virology laboratory of the Calcutta School of Tropical Medicine from
      different hospitals of Kolkata. IgM antibody capture ELISA was performed on the
      CSF and serum samples by JE virus MAC ELISA kit supplied by the National
      Institute of Virology, Pune. RESULTS: The present study reveals that 22.76% and
      5% of the AES cases were positive for JE IgM in 2011 and 2012, respectively. JE
      is mainly prevalent in children and adolescents below 20 years of age with no
      gender predilection. Although the percentages of JE positive cases were high in
      2011, it sharply decreased thereafter possibly due to better awareness programs,
      due to mass vaccination, or simply due to natural epidemiological niche
      periodicity due to herd immunity.

PMID- 24319694
TI  - Efficient haplotype block partitioning and tag SNP selection algorithms under
      various constraints.
AB  - Patterns of linkage disequilibrium plays a central role in genome-wide
      association studies aimed at identifying genetic variation responsible for common
      human diseases. These patterns in human chromosomes show a block-like structure,
      and regions of high linkage disequilibrium are called haplotype blocks. A small
      subset of SNPs, called tag SNPs, is sufficient to capture the haplotype patterns
      in each haplotype block. Previously developed algorithms completely partition a
      haplotype sample into blocks while attempting to minimize the number of tag SNPs.
      However, when resource limitations prevent genotyping all the tag SNPs, it is
      desirable to restrict their number. We propose two dynamic programming
      algorithms, incorporating many diversity evaluation functions, for haplotype
      block partitioning using a limited number of tag SNPs. We use the proposed
      algorithms to partition the chromosome 21 haplotype data. When the sample is
      fully partitioned into blocks by our algorithms, the 2,266 blocks and 3,260 tag
      SNPs are fewer than those identified by previous studies. We also demonstrate
      that our algorithms find the optimal solution by exploiting the nonmonotonic
      property of a common haplotype-evaluation function. 

PMID- 24319695
TI  - Antibacterial activity of defensin PaDef from avocado fruit (Persea americana
      var. drymifolia) expressed in endothelial cells against Escherichia coli and
      Staphylococcus aureus.
AB  - Antimicrobial therapy is a useful tool to control infectious diseases in general
      and rising antibiotic resistant microorganisms in particular. Alternative
      strategies are desirable, and antimicrobial peptides (AMP) represent attractive
      control agents. Mexican avocado (Persea americana var. drymifolia) is used in
      traditional medicine; however, the AMP production has not been reported in this
      plant. We obtained a cDNA library from avocado fruit and clone PaDef was
      identified, which has a cDNA (249 bp) encoding a protein (78 aa) homologous with
      plant defensins (>80%). We expressed the defensin PaDef cDNA (pBME3) in the
      bovine endothelial cell line BVE-E6E7. Polyclonal and clonal populations were
      obtained and their activity was evaluated against Escherichia coli,
      Staphylococcus aureus, and Candida albicans. E. coli viability was inhibited with
      100 MUg/mL of total protein from clones (>55%). Also, S. aureus viability was
      inhibited from 50 MUg/mL total protein (27-38%) but was more evident at 100
      MUg/mL (52-65%). This inhibition was higher than the effect showed by polyclonal
      population (~23%). Finally, we did not detect activity against C. albicans. These
      results are the first report that shows antimicrobial activity of a defensin
      produced by avocado and suggest that this AMP could be used in the control of
      pathogens.

PMID- 24319696
TI  - Skeletal muscle-specific CPT1 deficiency elevates lipotoxic intermediates but
      preserves insulin sensitivity.
AB  - OBJECTIVE: By specific knockout of carnitine palmitoyl transferase 1b (CPT1b) in
      skeletal muscles, we explored the effect of CPT1b deficiency on lipids and
      insulin sensitivity. METHODS: Mice with specific knockout of CPT1b in skeletal
      muscles (CPT1b M-/-) were used for the experiment group, with littermate C57BL/6
      as controls (CPT1b). General and metabolic profiles were measured and compared
      between groups. mRNA expression and CPT1 activity were measured in skeletal
      muscle tissues and compared between groups. Mitochondrial fatty acid oxidation
      (FAO), triglycerides (TAGs), diglycerides (DAGs), and ceramides were examined in
      skeletal muscles in two groups. Phosphorylated AKT (pAkt) and glucose transporter
      4 (Glut4) were determined with real-time polymerase chain reaction (RT-PCR).
      Insulin tolerance test, glucose tolerance test, and pyruvate oxidation were
      performed in both groups. RESULTS: CPT1b M-/- model was successfully established,
      with impaired muscle CPT1 activity. Compared with CPT1b mice, CPT1b M-/- mice had
      similar food intake but lower body weight or fat mass and higher lipids but
      similar glucose or insulin levels. Their mitochondrial FAO of skeletal muscles
      was impaired. There were lipids accumulations (TAGs, DAGs, and ceramides) in
      skeletal muscle. However, pAkt and Glut4, insulin sensitivity, glucose tolerance,
      and pyruvate oxidation were preserved. CONCLUSION: Skeletal muscle-specific CPT1
      deficiency elevates lipotoxic intermediates but preserves insulin sensitivity.

PMID- 24319697
TI  - Roles of Mitochondrial DNA Changes on Cancer Initiation and Progression.

PMID- 24319698
TI  - Designing Online Resources in Preparation for Authentic Laboratory Experiences.
AB  - Professional development for science teachers can be benefited through active
      learning in science laboratories. However, how online training materials can be
      used to complement traditional laboratory training is less understood. This paper
      explores the design of online training modules to teach molecular biology and
      user perception of those modules that were part of an intensive molecular biology
      "boot camp" targeting high school biology teachers in the State of Hawaii. The
      John A. Burns School of Medicine at the University of Hawaii had an opportunity
      to design and develop professional development that prepares science teachers
      with an introduction of skills, techniques, and applications for their students
      to conduct medical research in a laboratory setting. A group of 29 experienced
      teachers shared their opinions of the online materials and reported on how they
      used the online materials in their learning process or teaching.

PMID- 24319699
TI  - Designing and Developing Online Materials for Molecular Biology: Building Online
      Programs for Science.
AB  - A well-accepted form of educational training offered in molecular biology is
      internships in research laboratories. However, the number of available research
      laboratories severely limits access by most students. Addressing this need, the
      University of Hawaii launched a project to expand this model to include newly
      developed online training materials in addition to a hands-on laboratory
      experience. This paper explores the design and development process of the online
      learning materials. This case study looks at the roles of the instructional
      designer, multimedia specialist, and research faculty who were the subject matter
      experts. The experiences of the design teams are shared in an effort to gain
      insight on how the collaborative efforts of the project group led to a successful
      deployment of the online learning materials.

PMID- 24319700
TI  - Age-related peculiarities of adrenergic regulation of cardiac chronotropic action
      after I f blockage.
AB  - The effects of norepinephrine on the heart rate were studied in 1-, 3-, 6-, and
      20-week-old rats before and after blockade of hyperpolarization-activated
      currents (I f , I h ). In animals with mature sympathetic regulation of cardiac
      activity (6- and 20-week-old animals), I f blockage decreased the severity of
      norepinephrine-induced tachycardia. In newborn rats lacking sympathetic
      innervation of the heart, norepinephrine only slightly affected heart rate before
      and after I f blockage. In 3-week-old animals, I f blockage after norepinephrine
      pretreatment increased tachycardia.

PMID- 24319701
TI  - Effect of gold nanoparticles on production of reactive oxygen species by human
      peripheral blood leukocytes stimulated with opsonized zymosan.
AB  - We studied the effect of gold nanoparticles on ROS production by leukocytes. ROS
      production was detected by luminol-dependent chemiluminescence (LDCL) of human
      peripheral blood leukocytes stimulated with opsonized zymosan. Nanoparticle size
      was 5, 10 and 30 nm. Simultaneous addition of nanoparticles and opsonized zymosan
      showed that 5-nm nanoparticles inhibited LDCL intensity in comparison with the
      control, when LDCL recording was conducted in the presence of opsonized zymosan.
      Increasing nanoparticle size from 5 up to 30 nm enhanced LDCL intensity.
      Preincubation of gold nanoparticles with autologous blood plasma increased LDCL
      intensity. In the control (without gold nanoparticles), blood plasma produced no
      activating effect on LDCL. We found that the effect of gold nanoparticles on
      leukocyte LDCL depended on nanoparticle size: 10- and 30-nm nanoparticles
      inhibited LDCL intensity in comparison with the control (incubation in the
      absence of nanoparticles) irrespective of the duration of incubation, while 5-nm
      gold nanoparticles had no effect on LDCL intensity. Incubation of gold
      nanoparticles with autologous plasma increased LDCL intensity if nanoparticle
      size was 30 and 10 nm. 

PMID- 24319702
TI  - Pathogenic role of melatonin in sleep disorders in menopausal women.
AB  - The data on circadian rhythms of melatonin secretion in women of perimenopausal
      (n=39) and postmenopausal (n=52) age are presented. Each group was divided into
      control (without sleep disorders) and main group (with sleep disorders). The
      saliva was collected 4 times a day (6.00-7.00, 12.00-13.00, 18.00-19.00, 23.00
      24.00). The study revealed an association between sleep disorders and decreased
      level of melatonin only in women of perimenopausal age. 

PMID- 24319703
TI  - Dynamics of morpho-physiological changes in endocrine glands in pigs in postnatal
      period after treatment with biogenic substances.
AB  - Structural and functional features of the thyroid and adrenal glands of boars and
      hogs in postnatal period were determined by administration of bioactive
      substances Trepel and Suvar.

PMID- 24319704
TI  - Role of matrix metalloproteinases and their inhibitor in the development of early
      pulmonary fibrosis in mice infected with influenza A/H5N1
      A/goose/Krasnoozerskoye/627/05 virus.
AB  - High levels of macrophages and fibroblasts expressing MMP-2, MMP-9, and MMP-10
      against the background of progressing early fibrosis of the lungs (manifesting in
      an increase in volume density of type I, III, IV, and VI collagens) were found in
      C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus.
      Progressing fibrosis of the lungs in infected mice was associated with imbalance
      of collagen synthesis and degradation processes conjugated with high levels of
      macrophages and fibroblasts expressing TIMP-2. 

PMID- 24319705
TI  - The expression of matrix metalloproteinases in placental tissue depends on the
      severity of undifferentiated connective tissue dysplasia.
AB  - Immunohistochemical study of MMP-2 and MMP-9 expression in placental tissue of
      pregnant patients with undifferentiated connective tissue dysplasia of different
      severity showed that more severe condition was associated with higher expression
      of these MMP, this underlying the development of pregnancy and labor
      complications. The most pronounced elevation of the studied MMP levels was found
      in the basal plate decidual cells in women with undifferentiated connective
      tissue dysplasia of more than 18 score. 

PMID- 24319706
TI  - Method of cytogenetic assay of mouse oocytes.
AB  - We developed an original method of isolation and analysis of cytogenetic
      micropreparations of mouse oocytes including treatment with buffered hypotonic
      saline, paraformaldehyde fixation, and fluorescent staining. The method had
      several advantages, including high quality of sections and low labour intensity. 

PMID- 24319707
TI  - Therapeutic effect of mesenchymal multipotent stromal cells on memory in animals
      with Alzheimer-type neurodegeneration.
AB  - Transplantation of human mesenchymal multipotent stromal cells improved spatial
      memory in bulbectomized mice with Alzheimer-type neurodegeneration. The positive
      effect was observed in 1 month after intracerebral transplantation and in 3
      months after systemic injection of mesenchymal multipotent stromal cells. No
      cases of malignant transformation were noted. These findings indicate prospects
      of using mesenchymal multipotent stromal cells for the therapy of Alzheimer
      disease and the possibility of their systemic administration for attaining the
      therapeutic effect. 

PMID- 24319708
TI  - Adenoviral transduction of multipotent mesenchymal stromal cells from human
      adipose tissue with bone morphogenetic protein BMP-2 gene.
AB  - We determined conditions for effective transduction of multipotent mesenchymal
      stromal cells from human adipose tissue with adenoviral constructs carrying the
      gene of human bone morphogenetic protein BMP-2. The peak of transgene
      transcription and BMP-2 protein secretion in the transduced cultures was observed
      on day 6 after infection. The maximum transcription of BMP-2 gene and genes of
      osteogenic markers (bone sialoprotein, osteopontin, and osteocalcin) was observed
      in the medium containing sodium beta-glycerophosphate and ascorbic acid. Addition
      of D 3 vitamin did not enhance the expression of BMP-2 gene in transduced cells.
      The obtained cell cultures with high osteogenic potential can be used in bone
      tissue engineering. 

PMID- 24319709
TI  - Characteristics of cardiac cell cultures derived from human myocardial explants.
AB  - Primary cell cultures derived from human myocardial explants were obtained and
      characterized. The explant cultures contained cardiac stem cells (c-kit(+); ~
      4%), microvascular cells (endothelial cells and pericytes), fibroblasts, and
      myofibroblasts. It was demonstrated that culturing of cardiac cells in
      cardiospheres did not promote enrichment of the cell culture with stem cells.
      MACS-sorted c-kit(+) cells from the explant culture were characterized by limited
      proliferative capacity and were capable of cardiomyogenic differentiation. The
      presence of microvascular cells determined general angiogenic potential of the
      culture.

PMID- 24319710
TI  - Differentiation of dissociated rat embryonic brain after allotransplantation into
      damaged nerve.
AB  - Fragments of the dorsolateral wall of the anterior brain vesicle from rat embryos
      on embryonic day 15 were dissociated and the resultant suspension containing
      single cells and cell aggregates was injected into the proximal segment of
      crushed sciatic nerve of adult animals for evaluation of their engrafting and
      differentiation under conditions of changed microenvironment. On days 1 and 21
      postoperation, Msi-1, GFAP, NeuN, vimentin, and PCNA were detected by
      immunohistochemical methods. Small clusters of Msi-1-immunopositive cells were
      detected in the nerve trunks on the next day after transplantation. On day 21
      after surgery, these precursors differentiate into nerve cells, astrocytes, and
      primarily ependymocytes. 

PMID- 24319711
TI  - Cell therapy of refractory Crohn's disease.
AB  - We analyzed medium-term efficiency and safety of biological therapy of Crohn's
      disease, in particular transplantation of allogenic mesenchymal stromal bone
      marrow cells and anticytokine therapy with selective immunosuppressive agents. It
      was found that both methods of biological therapy of refractory Crohn's disease
      resulted in clinical and in some cases endoscopic remission. In most cases,
      clinical remission was maintained without steroid hormone therapy. Thus, both
      methods produce comparable clinical results. It was concluded that
      transplantation of mesenchymal stromal bone marrow cells could be considered as a
      promising method in the therapy of refractory Crohn's disease comparable by its
      efficiency with infliximab therapy. 

PMID- 24319712
TI  - Human platelet lysate as a promising growth-stimulating additive for culturing of
      stem cells and other cell types.
AB  - We compared the composition and biological activity of fetal calf serum and
      platelet lysate from donor platelet concentrate. In platelet lysate, the
      concentrations of alkaline phosphatase, lactate dehydrogenase, creatinine, and
      mineral metabolism parameters were lower, while parameters of lipid and protein
      metabolism were higher than in fetal calf serum. The concentrations of growth
      factors (platelet-derived (AA, AB, BB), vascular endothelial, insulin-like, and
      transforming growth factor beta) in platelet lysate 1.7-148.7-fold surpassed the
      corresponding parameters in fetal calf serum. After replacement of fetal calf
      serum with platelet lysate in the culture medium (0, 25, 50, 75, and 100%), the
      count of multipotent mesenchymal stromal cells on day 7 (in comparison with day
      1) increased by 154.8, 206.6, 228.2, 367.7, and 396.5%, respectively. Thus,
      platelet lysate can be an adequate non-xenogenic alternative for fetal calf
      serum.

PMID- 24319713
TI  - Role of cytochrome P450-dependent monooxygenases and polymorphic variants of
      GSTT1 and GSTM1 genes in the formation of brain lesions in individuals
      chronically exposed to mercury.
AB  - The metabolic test with antipyrine was performed, the relationship between
      genotypes of GSTT1 and GSTM1 polymorphisms were studied, and cotinine level was
      measured in 116 men chronically exposed to mercury. The individuals were divided
      in 4 groups depending on the diagnosis of chronic mercury intoxication. The
      changes in the parameters of antipyrine test were studied in linked samples
      (N=62, 4 year interval); in patients with chronic mercury intoxication, the
      disease stage was taken into account. Inhibition of antipyrine metabolism,
      increased frequency of combination of GSTT1(0/0)/GSTM1(+) genotypes in patients
      with chronic mercury intoxication, and the specificity of cytochrome P450
      inhibition with mercury suggest that disease progression is related to inhibition
      of cytochrome P450 isoforms in the brain that catalyze regulation of endogenous
      substrates. 

PMID- 24319714
TI  - Modification of collagen formation by mesenchymal stem cells isolated from human
      adipose tissue in culture and after autotransplantation for abdominal hernia
      plasty.
AB  - Mesenchymal stem cells from the adipose tissue of patients with postoperative
      hernias produce excessive amounts of collagen III, which shifts the balance
      between type III and type I collagens. The proposed technique of
      pretransplantation preparation allows in vitro stimulation collagen formation
      processes with predominant activation of collagen I synthesis and normalization
      of proportion between different collagen types. Abdominal wall repair with
      polypropylene surgical mesh in combination with autotransplantation of
      mesenchymal stem cells reduced the collagen III to collagen I ratio due to
      activation of collagen I synthesis and suppression of collagen III production,
      which had a positive effect on the structure of in vivo formed connective tissue.

PMID- 24319715
TI  - Effect of placenta secretory products on migration activity of endothelial
      EA.Hy926 cells.
AB  - We studied the influence of factors secreted by the placenta in physiological and
      preeclampsia-complicated pregnancy on migration activity of endothelial EA.Hy926
      cells. It was found that migration of endothelial cells was more intensive in the
      presence of secretory factors from trimester I placentas in comparison with
      trimester III placentas and was lower in the presence of placental factors in
      preeclampsia in comparison with physiological pregnancy. 

PMID- 24319716
TI  - Effect of mature dendritic cells primed with autologous tumor antigens from
      patients with epithelial ovarian cancer on stimulation of the cytotoxic immune
      response in culture of mononuclear cells.
AB  - For modulation of antitumor cytotoxic activity of mononuclear cells in vitro,
      autologous dendritic cells loaded with tumor lysate antigens were cultured with
      peripheral blood mononuclear cells from patients with epithelial ovarian cancer
      in the presence or absence of IL-12 and IL-18. The efficiency of modulation was
      evaluated by cytotoxic activity of mononuclear cells against autologous tumor
      cells, by the production of IFN-gamma, IL-4, and by the count of perforin
      containing lymphocytes. It was demonstrated that dendritic cells stimulated
      cytotoxic immune response in mononuclear cell culture. Maximum induction of
      cytotoxic activity of mononuclear cells was attained in case of dendritic cells
      combination with IL-12 and IL-18 (increased death of autologous tumor cells,
      accumulation of perforin-positive lymphocytes, enhanced production of IFN-gamma).

PMID- 24319717
TI  - Characteristics of new monomolecular chimeric T-cell receptors to
      carcinoembryonic antigen.
AB  - We described two original genetic constructs encoding chimeric monomolecular T
      cell receptors, where the effector T-cell receptor fragment was linked with the
      antigen-recognizing part consisting of two variable fragments of two different
      antibodies to carcinoembryonic antigen. Following transfection, these receptors
      were expressed on the cell surface and bound carcinoembryonic antigen. Human
      peripheral blood lymphocytes transfected with the above constructs demonstrated
      high cytotoxic activity against HCT116 cells expressing carcinoembryonic antigen.

PMID- 24319719
TI  - Saccadic movements of the eyes in children with attention deficit and
      hyperactivity syndrome.
AB  - Saccadic movements of the eyes were analyzed in children with the attention
      deficit and hyperactivity syndrome. Saccadic movements of the eyes were recorded
      by a special method for their isolated registration without involvement of the
      head and in coordination tests (eye-head, eye-hand, and eye-head-hand).
      Comparative analysis of saccadic movements in children with attention deficit and
      hyperactivity and in normal subjects was carried out. Saccades recorded in each
      participant in complex tests with one or two additional motor acts, such as
      movements of the head and hand, were compared and the changes were analyzed for
      the group. Children with attention deficit and hyperactivity syndrome had problem
      with gaze fixation on the peripheral target after the end of the saccade and
      these changes augmented in more complex tasks with one or two additional acts.
      This could be due to discrepancy between the difficulty of the task and the
      potentialities of the frontal cortex, more immature in these patients than in
      healthy children. The changes could form the objective base for disorders in the
      formation of reading and writing habits, often observed in children with
      attention deficit and hyperactivity syndrome. 

PMID- 24319718
TI  - Effect of metalloproteinase inhibitor on early postinfarction remodeling in the
      most acute phase of myocardial infarction.
AB  - Echocardiography in control narcotized rats (n=12) revealed that acute single
      stage ligation of coronary artery induced a rapid and significant decrease in
      systolic function of the heart, which attained minimum to postischemic minutes 10
      20 and then gradually restored during 60 min after coronary occlusion. Matrix
      proteinase inhibitor doxycycline (40 mg/kg/day intragastrically for 3 days prior
      to the experiment) prevented dramatic impairment of systolic function in the left
      ventricle during first 20 min of ischemia and then all the indices characterizing
      the state of pumping function of the left ventricle in the experimental
      (doxycycline) group (n=9) surpassed the control. Thus, matrix proteinase
      inhibitor doxycycline prevented early postischemic remodeling of the heart during
      the most acute phase of experimental myocardial infarction. 

PMID- 24319720
TI  - Effects of glucocorticoid antagonist on protein carbonylation in rat liver after
      daily 1-hour immobilizations.
AB  - Daily (for 3 days) 1-hour immobilizations were followed by an increase in protein
      oxidative modification and leukocyte infiltration in the liver, and a decrease in
      monoamine oxidase B activity. Receptor antagonist of glucocorticoids RU38486
      limited the stress-induced increase in protein carbonylation and decrease in
      monoamine oxidase B activity in the organ and enhanced leukocyte infiltration of
      the liver. 

PMID- 24319721
TI  - Effects of erythrocyte microvesicles on the coagulation process stages.
AB  - We studied the effect of erythrocyte microvesicles on various stages of platelet
      free autoplasma coagulation process. The erythrocyte microvesicles not only
      exhibited procoagulant activity, but also produced a pronounced anticoagulant
      effect by inhibiting fibrin formation process. The effects of microvesicles
      isolated from erythrocytes after 24- and 48-hour cell storage on plasma
      coagulation were different. The hemocoagulation effects of the "light" and
      "heavy" microvesicles were studied. 

PMID- 24319722
TI  - Effects of dehydroepiandrosterone sulfate on blood pressure and aldosterone level
      via MU-opioid receptors.
AB  - Dehydroepiandrosterone sulfate (30 mg/kg) produced a hypotensive effect by
      preventing stress-induced surge of hypertensive hormone aldosterone in rats after
      manifold repeated, but not single stress exposure. Both effects were realized via
      MU-opioid receptors. Thus, MU-opioid mechanism of blockage of aldosterone surge
      can underlay the hypotensive effects of dehydroepiandrosterone sulfate at least
      under conditions of manifold repeated exposures. 

PMID- 24319723
TI  - Dopamine disorganizes the rhythm of protein synthesis disrupting self
      organization of hepatocytes in vitro.
AB  - We studied dense 24-hour cultures of rat hepatocytes in serum-free medium on
      collagen-coated slides. As before, a circahoralian rhythm of protein synthesis
      was observed in control cultures in a fresh medium. No rhythm was found after
      addition of 1-10 MUM dopamine to the medium containing such cultures. The rhythm
      was observed after addition of 0.3 MUM ganglioside to pretreated-dopamine
      cultures. Dopamine is likely to influence the conditioning of intercellular
      medium with gangliosides. Deficit of this endogenous synchronizing factor in the
      intercellular medium blocks self-organization of the protein synthesis rhythm.
      Thus, in contrast to previously studied norepinephrine and serotonin, as well as
      gangliosides, which organized the population rhythm of protein synthesis,
      dopamine disorganized the rhythm, impairing direct intercellular interactions. 

PMID- 24319724
TI  - Aminopyridine lengthened the plateau phase of action potentials in mouse
      sinoatrial node cells.
AB  - Duration of the plateau phase (phase 2) of action potentials in pacemaker cells
      in mouse sinoatrial node characterized by low upstroke rate during the rapid
      depolarization (dV/dt max <7 V/sec, phase 0) and in atrial-like cells with dV/dt
      max <100 V/sec were prolonged by 50% with 4-aminopyridine in concentrations of
      0.7 and 0.1 mM, respectively. This blocker did not lengthen the terminal
      repolarization (phase 3). The above changes were accompanied by a 20-80% decrease
      in dV/dt max in comparison to the control. It is hypothesized that the short-term
      (transient) outward current Ito takes a part in the plateau formation and
      modulates the duration of the rapid depolarization phase of action potentials in
      mouse sinoatrial node cells.

PMID- 24319725
TI  - Influence of singlet oxygen inhalation on the state of blood pro- and antioxidant
      systems and energy metabolism.
AB  - Activity of lactate dehydrogenase in direct and reverse reactions, activity of
      aldehyde dehydrogenase, blood lactate and glucose levels, pro- and antioxidant
      balance in the blood were analyzed in rats after inhalations of singlet oxygen
      for 10 days. The course of inhalations improves antioxidant reserve of the blood
      and activity of blood oxidoreductases in healthy animals, thus strengthening the
      adaptive potential of the body. 

PMID- 24319726
TI  - Aptamer RA36 inhibits of human, rabbit, and rat plasma coagulation activated with
      thrombin or snake venom coagulases.
AB  - RA36 DNA aptamer is a direct anticoagulant prolonging clotting time of human,
      rabbit, and rat plasma in the thrombin time test. Anticoagulant activity of RA36
      is lower than that of recombinant hirudin. During inhibition of human plasma
      clotting activated with echitox (coagulase from Echis multisquamatus venom), the
      aptamer presumably binds to meisothrombin exosite I. The sensitivity of human
      plasma to the aptamer 5-fold surpasses that of rat plasma. Analysis of RA36
      binding to coagulase of Agkistrodon halys venom (ancistron) is required for
      proving the effect of aptamer on polymerization of human fibrinogen. 

PMID- 24319727
TI  - Effect of toll-like receptor agonists on the formation of macrophage/foam cells
      upon acute peritonitis in mice.
AB  - We studied effects of zymosan, double-stranded RNA, LPS of E. coli and bacterial
      CpG DNA, agonists of toll-like receptor TLR2, TLR3, TLR4 and TLR9, respectively,
      on the formation of macrophage/foam cells 24 h after induction of acute
      peritonitis. Administration of agonists led to transformation of peritoneal
      macrophages into foam cells and significant activation of cell biosynthesis and
      increased the content of triglycerides and cholesterol esters in the absence of
      LDL and irrespective of the capacity of TLR agonists to stimulate neutrophil
      infiltration and TNF-alpha production in the peritoneal cavity. 

PMID- 24319728
TI  - Anti-inflammatory and antifibrotic effects of a combination of spiperone and
      immobilized hyaluronidase on partially reversible and irreversible toxic
      pneumofibrosis.
AB  - The possibility of boosting antifibrotic activity of testicular hyaluronidase
      immobilized on polyethylene oxide with spiperone was studied on the bleomycin
      models of a single (partially reversible pneumofibrosis) and repeated
      (irreversible pneumofibrosis) injuries to the alveolar epithelium in C57Bl/6
      mice. The antifibrotic effect was more pronounced after successive treatment with
      immobilized hyaluronidase and spiperone than after individual treatment with each
      of the compounds: no collagen deposition in the parenchyma of bleomycin-damaged
      lungs was found. The decrease in inflammatory cell (lymphocytes, macrophages,
      neutrophils, plasma cells) infiltration of the alveoli and alveolar tracts
      interstitium in mice treated by immobilized hyaluronidase and spiperone did not
      differ from the anti-inflammatory effect of spiperone monotherapy. 

PMID- 24319729
TI  - Neuroprotective effects of heptapeptide mystixin.
AB  - Neuroprotective effects of heptapeptide mystixin were studied on the neurons of
      the olfactory cortex in cultured slices of rat brain. Repeated applications of
      mystixin in doses of 100 mg/ml on brain slices rapidly reduced the amplitudes of
      AMPA and NMDA receptor-dependent processes. The effects were reversible and
      activities of these processes partly restored after washout. The peptide in a
      dose of 250 mg/ml suppressed epileptic discharges induced by chemical convulsive
      agent pentylenetetrazole. Thus, heptapeptide mystixin exhibited significant
      neuroprotective properties. 

PMID- 24319730
TI  - Effects of simvaglyzin and atorvaglyzin on the expression of 3-hydroxy-3-methyl
      glutaryl-CoA reductase in rat liver.
AB  - Activity and levels of protein and mRNA of 3-hydroxy-3-methyl-glutaryl-CoA
      reductase were estimated in rat liver after the administration of atorvastatin
      and simvastatin and their complexes with glycyrrhizic acid (atorvaglyzin and
      simvaglyzin). The amount of 3-hydroxy-3-methyl-glutaryl-CoA reductase protein in
      rats decreased by 13 and 25% (p<0.05) 24 h after treatment with atorvaglyzin and
      simvaglyzin, respectively. Activity of this enzyme decreased by 46% in rats
      treated with atorvaglyzin. The amount of messenger RNA in these groups
      significantly increased as compared to control group (untreated animals).

PMID- 24319731
TI  - Effects of activation of maternal immune system at early stages of pregnancy on
      antitumor immunity of the progeny.
AB  - The effects of maternal immune system on the formation and functioning of the
      fetus is an important problem. Single stimulation of immune system of female
      C57Bl/6 mice with concanavalin A at the early stages of pregnancy before the
      formation of fetal immune organs was followed by impairment of antitumor immunity
      in the progeny by the time of puberty. These changes manifested in the increased
      survival rate of B16 melanoma, high rate of death of tumor-bearing animals, and
      low cytotoxic activity of spleen cells on L-929 fibrosarcoma cells. 

PMID- 24319732
TI  - Effect of interleukin-4 on antioxidant protection of the brain in rats during
      acute emotional stress.
AB  - We studied the effect of IL-4 on antioxidant enzyme activity in brain structures
      (hypothalamus, sensorimotor cortex, and amygdala) in behaviorally passive and
      active rats. One-hour immobilization of animals with simultaneous delivery of
      subthreshold electrocutaneous stimulation was used as the model of acute stress.
      Intraperitoneal injection of IL-4 (5 MUg/kg) was followed by an increase in
      activities of glutathione peroxidase and Cu/Zn SOD in the hypothalamus of non
      stressed rats. Activities of glutathione peroxidase and Cu/Zn SOD in the amygdala
      were shown to decrease. Administration of IL-4 was accompanied by activation of
      glutathione peroxidase (active and passive rats), glutathione reductase (passive
      rats), and Cu/Zn SOD (active rats) in the sensorimotor cortex. These data
      indicate that the efficiency of antioxidant protection increases in the
      hypothalamus and sensorimotor cortex, but decreases in the amygdala of rats
      receiving IL-4. Pretreatment with IL-4 abolished a poststress increase in
      glutathione peroxidase activity in the sensorimotor cortex of passive animals. 

PMID- 24319733
TI  - Integral approach to evaluation of the pathogenic activity of Trypanosoma cruzi
      clones as exemplified by the Mexican strain.
AB  - Comparative histopathological study and analysis of parasite load in different
      muscle groups were carried out in BALB/c mice during the acute phase of Chagas
      disease. Activities of C104 clone of T. cruzi strain TPAP/MX/2002/Albarrada and
      the parental strain were compared. Panoramic 2D-microscopy imaging of sample
      surface was used and quantitative analysis of parasitism and pathologic damage
      was performed. The infection rates in various muscle groups were as follows:
      myocardium=abdominal muscles=lumbar muscles=femoral muscles<--diaphragm for the
      clone and myocardium!abdominal muscles=lumbar muscles=femoral muscles-->diaphragm
      for the parental strain.

PMID- 24319734
TI  - Proliferative activity and subpopulation pattern of cells in murine thymus and
      spleen on the model of graft-versus-host chronic reaction under various diurnal
      regimens of IL-2 administration.
AB  - We studied the effects of IL-2 administration at different times of day to female
      B6D2F1 mice with experimental immunopathology, graft-versus-host chronic reaction
      induced by the administration of lymphoid cells from parental female DBA/2 mice.
      Recombinant murine IL-2 was injected subcutaneously at 10.00 (group 1) or 16.00
      (group 2) after the first cell transfer. Evening administration of IL-2 in
      contrast to its morning injection prevented cell proliferation in the thymus and
      spleen, decreased the number of apoptotic splenocytes, significantly stimulated
      differentiation processes in the thymus, increased the amount of CD4 (+) 25
      (high) thymocytes, and decreased the number of CD4 (+) 27 (low) splenocytes.
      These findings can serve as a prerequisite for the development of
      chronotherapeutic schemes for immunocorrection. 

PMID- 24319735
TI  - Comparative phenotypic and cytochemical characteristics of lymphocytes of Wistar
      rats and rats with genetic predisposition to catalepsy after retabolil
      administration.
AB  - We studied the possibility of using anabolic steroid retabolil injections for
      complex correction of behavioral and immune parameters in rats with genetic
      predisposition to catalepsy. Subpopulation composition of lymphoid organ and
      blood cells was compared in rats with genetic predisposition to catalepsy and
      Wistar rats after retabolil administration. In rats predisposed to catalepsy,
      retabolil reduced the total content of thymus cells and increased absolute count
      of CD8 (+) thymocytes. In Wistar rats, retabolil increased the total cell count
      and the content of CD4 (+) thymocytes, but reduced the number of CD8 (+) cells.
      Therefore, changes in the subpopulation composition of thymus cells after
      retabolil administration were opposite in rats with genetic predisposition to
      catalepsy and Wistar rats. Retabolil injections reduced the severity of catalepsy
      response in rats with genetic predisposition. However, the time of freezing in
      Wistar rats significantly increased under these conditions. 

PMID- 24319736
TI  - Relationship between the argyrophilic proteins of the nucleolar organizer region
      and stage of squamous-cell carcinoma of the lung.
AB  - Argyrophilic proteins associated with chromosome nucleolar organizer regions (Ag
      NOR proteins) were studied in lung squamous-cell carcinoma cells. After routine
      staining with silver nitrate, the area index and coefficient of variations of Ag
      NOR protein were estimated by computer-aided image analysis. The Ag-NOR protein
      area indexes of tumor cells differed in clinical morphological variants of
      squamous-cell cancer (differing by T and N parameters, size of the primary node
      <3 cm or larger, by disease stage, and differentiation degree). Ag-NOR protein
      variation coefficient can be used for discriminating the tumors by size (<3 cm
      and larger), presence/absence of metastases, and evaluation of squamous-cell
      cancer differentiation degree. Ag-NOR protein area index and variation
      coefficient can be used as additional objective differential diagnostic criteria
      of clinical and morphological forms of squamous-cell carcinoma of the lung. 

PMID- 24319737
TI  - Activation of cathepsins B and L in mouse lymphosarcoma tissue under the effect
      of cyclophosphamide is associated with apoptosis induction and infiltration by
      mononuclear phagocytes.
AB  - We analyzed activities of lysosomal cystein cathepsins B and L in mouse LS
      lymphosarcoma and its drug-resistant RLS 40 strain and their correlations with
      the dynamics of the percentage of cells with fragmented DNA and CD14 (+)
      phagocytes over 3 days after cyclophosphamide injection. LS regression and
      inhibition of RLS 40 growth after cyclophosphamide injection were paralleled by
      an increase in cathepsins B and L activities in tumor tissues. The antitumor
      effect of cyclophosphamide associated with apoptosis intensity and protease
      activities were significantly higher in LS. Positive correlations between
      activities of cathepsins B and L and the LS tissue content of cells with
      fragmented DNA and CD14 (+) phagocytes and negative correlations thereof with
      tumor weight were detected. It seems that the increase in cathepsins B and L
      activities in LS tissues was caused by cyclophosphamide induction of apoptosis
      and depended on the level of tumor cell infiltration with mononuclear phagocytes.

PMID- 24319738
TI  - Effects of low-dose radiation on glutamate dehydrogenase activity in tissues of
      rats with transplanted Guerin's carcinoma.
AB  - Glutamate dehydrogenase activity in mitochondrial fraction of the liver and
      muscle tissue of tumor-bearing rats was studied in the dynamics of Guerin's
      carcinoma growth and after preliminary low-dose irradiation. At the initial
      stages of Guerin's carcinoma growth, maximum activity of glutamate dehydrogenase
      was observed in the liver, while in the muscle tissue, catabolic transformations
      of amino acids was activated at the logarithmic phase of carcinogenesis and
      tended to inhibition at the terminal stages. Low-dose irradiation was followed by
      activation glutamate dehydrogenase in mitochondrial fraction of the liver and
      inhibition of this enzyme in mitochondrial fraction of the muscle tissue. 

PMID- 24319739
TI  - Blood microvesicles during chronic lymphoproliferative diseases.
AB  - The levels of CD19 (+) and CD20(+) microvesicles were estimated in the blood of
      patients with B-cell chronic lymphocytic leukemia and indolent non-Hodgkin
      lymphoma by flow cytometry method. It was found that the number of B cell
      microvesicles is several times higher in patients than in volunteers. The level
      of CD20 (+) microvesicles directly correlated with the number of CD20(+)
      lymphocytes in patients with chronic lymphoproliferative diseases. Extramedullary
      tumors cells can be a source of CD19 (+) microvesicles. 

PMID- 24319740
TI  - Serum metabolic profiles of pregnant women with burdened obstetrical history.
AB  - The content of low-molecular-weight components in blood serum was studied by
      tandem mass-spectrometry in pregnant women. Serum metabolic profiles of patients
      with a grave obstetrical history were detected. The most significant changes were
      observed for the concentrations of low-molecular-weight substances involved in
      glucogenesis and beta-oxidation processes and in metabolic chains involving
      carbohydrates, carnitines, amino acids, and lipids. 

PMID- 24319741
TI  - Inotropic effect of dopamine on rat heart during postnatal ontogeny.
AB  - We studied the effect of dopamine in concentrations of 10(-9), 10(-8), 10(-7),
      10(-6), and 10(-5) M on contraction strength of isolated myocardial strips from
      the right atrium and right ventricle of rats aging 21, 42, 56, and 100 days.
      Dopamine in a concentration of 10(-9) M had a positive inotropic effect in rats
      of various ages. Increasing the concentration of dopamine to 10(-7)-10(-5) M was
      accompanied by a negative inotropic effect on the heart. 

PMID- 24319742
TI  - Effect of mifepristone on glucocorticoid receptor gene expression in the liver of
      rats with streptozotocin-induced diabetes.
AB  - The effects of mifepristone on activity of the adrenocortical system, expression
      of glucocorticoid receptor gene, and tyrosine aminotransferase activity in the
      liver were studied in rats with streptozotocin-induced diabetes. Administration
      of glucocorticoid receptor blocker mifepristone to rats without diabetes was
      followed by a 1.9-fold increase in serum corticosterone concentration and a 1.2
      fold increase in tyrosine aminotransferase activity in the liver in comparison
      with the baseline values. In rats with streptozotocin-induced diabetes,
      mifepristone produced a less pronounced increase in the corticosterone
      concentration (by 1.5 times) and more drastic increase in enzyme activity (by 1.7
      times). Mifepristone administration did not change the content of glucocorticoid
      receptor mRNA in the liver of rats without diabetes, but increase this parameter
      by 1.4 times in rats with streptozotocin-induced diabetes. The enhanced
      expression of glucocorticoid receptor gene in the liver of rats with
      streptozotocin-induced diabetes correlated with increased activity of tyrosine
      aminotransferase after mifepristone treatment. 

PMID- 24319743
TI  - Cytochrome P450 4F2 polymorphism in patients with liver cirrhosis.
AB  - 1297C/T polymorphism of CYP4F2 gene was studied in 108 patients with chronic
      liver diseases. No significant correlation with predisposition to rapid liver
      cirrhosis was revealed without consideration for cirrhosis etiology (OR=0.93, 95%
      CI=0.28-2.99, p=0.885). In patients with viral cirrhosis, a tendency to
      association of 1297T allele genotypes with rapid cirrhosis development was found
      (OR=6.0, 95% CI=0.28-382.64, p=0.222). At the same time, CYP4F2 1297T allele was
      associated with mild (Child-Pugh class A-B) cirrhosis (OR=2.9, p=0.044). 

PMID- 24319744
TI  - Comparative study of changes in energy metabolism in rat cardiomyocytes in
      postinfarction cardiosclerosis and diabetes mellitus.
AB  - Cardiomyocyte energy metabolism in experimental unfolding postinfarction
      cardiosclerosis and diabetes mellitus was studied. Postinfarction cardiosclerosis
      formed 6 weeks after coronary artery occlusion. Diabetes mellitus was induced by
      intraperitoneal injection of streptozotocin (60 mg/kg). The rate of oxygen
      consumption in postinfarction cardiosclerosis and diabetes increased by 3.4 and
      4.2 times, respectively. Stimulation of mitochondrial respiration (ATP, palmitic
      acid) significantly increased oxygen consumption in animals with postinfarction
      cardiosclerosis and significantly reduced this process in diabetes. The content
      of LDH and SDH in the myocardium of animals with diabetes and postinfarction
      cardiosclerosis was significantly below the control. Hence, the development of
      postinfarction cardiosclerosis and diabetes mellitus were characterized by
      reduced generation of ATP in anaerobic and aerobic pathways and oxidative
      phosphorylation in cardiomyocytes. 

PMID- 24319745
TI  - Correlation between circulating corticosterone and protein carbonylation in the
      liver after short-term hypokinesia.
AB  - We studied the correlation of the concentration of circulating corticosterone and
      parameters of dexamethasone suppression test with the level of protein
      carbonylation in the liver after short-term hypokinesia. Increasing hypokinesia
      duration was followed by worsening of disturbances in the hypothalamic-pituitary
      adrenal system via a negative feedback mechanism and enhanced protein
      carbonylation in the liver. 

PMID- 24319746
TI  - Role of cytochrome b5 and alpha-tocopherol to microsomal and mitochondrial
      oxidation.
AB  - The existence of lipid-radical cycles in membranes as an LPO alternative has been
      proven. Cytochrome b5 seems to play the key role in the formation of these
      cycles. The functional role of lipid-radical cycles in cell metabolism, including
      the positive effect on microsomal and mitochondrial oxidation, is discussed. 

PMID- 24319747
TI  - Effects of zinc on the content of chemical elements in the liver of rats during
      early stages of obesity.
AB  - In rats with slight alimentary obesity, the content of chemical elements in the
      liver did not differ from normal, but the correlations between these elements
      were changed, which attested to metabolic disorders. Additional zinc dose
      administered to rats receiving lipid-rich rations did not affect animal body
      weights and content of chemical elements (including zinc) in the liver, but
      corrected correlations between the elements. Active contribution of strontium,
      bromine, and rubidium to interactions between the elements in the liver
      necessitates studies of their role in biological processes, specifically, in
      initiation and development of obesity. 

PMID- 24319748
TI  - Changes of protein profile of human urine after long-term orbital flights.
AB  - We analyzed protein profile of urine samples obtained from 7 Russian cosmonauts
      (age 35-51 years), participants of space flights on the International Space
      Station lasting for 169-199 days. Gradient chromatography with linear increase of
      eluent proportion was carried out in a system consisting of an Agilent 1100
      chromatograph (Agilent Technologies Inc.) and a hybrid mass-spectrometer LTQ-FT
      Ultra (Thermo). The obtained results help to understand changes in the human body
      induced by space flight factors. 

PMID- 24319749
TI  - Effects of endogenous regulators of endothelial NO synthase on nitric oxide
      homeostasis and blood serum lipoproteins during experimental diabetes mellitus.
AB  - Experimental diabetes mellitus was associated with the development of oxidative
      stress and a decrease in blood concentration of total nitric oxide (NO)
      metabolites. Administration of L-arginine induced positive changes in the LPO
      antioxidant enzyme system and elevated NO concentration in blood serum, whereas L
      NAME, inhibitor of eNOS (NOS-III) increased LPO intensity via SOD inhibition and
      reduced NO content. Combined administration of Q10 and L-arginine led the
      suppression of oxidative stress and significant increase in NO level. Combined
      treatment with Q10 and L-NAME partly abolished the effects of the inhibitor on
      the parameters of the LPO-antioxidant enzyme system and NO concentration. In all
      variants of the study, Q10 stimulated eNOS expression and increases NO
      bioavailability by reducing the levels of total cholesterol and LDL and
      increasing HDL content in blood serum. 

PMID- 24319750
TI  - Effect of long-term treatment with beta-adrenoceptor antagonists on blood lipid
      composition and survival of rats with heart failure of different severity.
AB  - Plasma LDL content increased in rats with mild chronic heart failure, but
      decreased in animals with severe pathology. The lipid profile of beta
      adrenoceptor antagonists depended on their selectivity. The most selective
      antagonists of beta-adrenoceptors had little effect on the lipid composition.
      Nonselective beta-adrenoceptor antagonists increased the index of plasma
      atherogenicity, which did not depend on the severity of a pathological process.
      In mild chronic heart failure, these changes were associated with a decrease in
      HDL concentration, while in severe chronic heart failure; they were related to a
      tendency towards a decrease in HDL content and an increase in LDL concentration.
      The increase in survival rate was associated with true antagonism of the agent to
      beta-adrenoceptors (the absence of intrinsic sympathomimetic activity) and, to a
      lesser extent, with nonselective blockade of beta-adrenoceptors. 

PMID- 24319751
TI  - Ridostin induces transcription of a wide spectrum of interferon genes in human
      cells.
AB  - The effects of Ridostin on the transcription of IFN family genes in human
      fibroblasts and lymphocytes were studied by quantitative real-time PCR. The
      degree of gene induction by Ridostin was most pronounced in fibroblasts, and was
      significantly higher than the induction by Kagocel: transcription of IFN-beta,
      oligoadenylate synthetase, and double-stranded RNA-dependent protein kinase genes
      increased by about 2000, 100, and 20 times, respectively. In lymphocytes,
      Ridostin also activated a wide variety of IFN family genes, including genes of
      IFN-beta, IFN-gamma, and IFN-dependent enzymes, but this induction was less
      pronounced than in the fibroblasts. It was shown that gene response in lymphocyte
      from a child with cancer is reduced in comparison with that of adult healthy
      participant. Ridostin, and even more so Reaferon up-regulated activities of beta
      actin, glycerophosphate dehydrogenase, and beta2-microglobulin genes, thus making
      impossible or limiting their use as constitutive stable reference genes
      (standards) in PCR-assays of IFN and their inductors. 

PMID- 24319752
TI  - Contra-insular effect of calcitonin on glucose metabolism.
AB  - We studied the effects of Russian preparation of porcine calcitonin (Calcitrinum,
      1 U/100 g) on the level of glucose and total calcium, glycogen concentration in
      the liver, and glucose consumption by the muscle and adipose tissues in vivo and
      in vitro. The basal level of insulin and secretion of insulin in the dynamics of
      glucose tolerance test were studied after treatment with calcitonin. In addition
      to hypocalcemic effect, this substance produced significant hyperglycemic
      effects, decreased glycogen amount in the liver, inhibited insulin-induced
      glucose consumption by muscular and adipose tissues in vivo and in vitro, slowed
      down insulin secretion during glucose load, and impaired glucose tolerance. Thus,
      calcitonin had contra-insular effects on glucose metabolism. 

PMID- 24319753
TI  - In vivo analysis of antioxidant and prooxidant properties of retinol acetate.
AB  - Analysis of the effects of retinol acetate on LPO processes in vivo revealed
      antioxidant effects under normal conditions and during experimental free-radical
      pathology (toxic hepatosis-hepatitis). The concentration inversion of antioxidant
      effects of retinol acetate into prooxidant effects were observed only under
      normal conditions. 

PMID- 24319754
TI  - Mechanisms of intracellular defense and activity of free radical oxidation in rat
      myocardium in the dynamics of chronic fluorine intoxication.
AB  - The mechanisms of intracellular defense and activity of free radical oxidation in
      the myocardium were studied in the dynamics of chronic fluorine intoxication. At
      the early stages of fluorine intoxication (day 3-week 3), the concentrations of
      defense proteins HIF-1alpha, HSC73, and HOx-2 and activity of the main metabolic
      enzymes increased, which promoted maintenance of cardiomyocyte structure and
      function at the normal physiological level. At late stages of fluorine
      intoxication (weeks 6 and 9), metabolic changes in the myocardium attest to high
      strain of the adaptive mechanisms. 

PMID- 24319755
TI  - Role of cAMP and IKK-2-dependent signaling in the realization of growth potential
      of mesenchymal progenitor cells.
AB  - We studied the role of cAMP- and IKK-2-mediated pathways in the realization of
      growth potential of mesenchymal progenitor cells in vitro. It had been found that
      adenylate cyclase inhibitor 2',5'-dideoxyadenosine had no effect on the
      proliferation and differentiation of fibroblastic CFU. A decrease in
      differentiation rate of progenitor cells was observed after the treatment with
      specific IKK-2 blocker inhibitor-kinase complex. 

PMID- 24319756
TI  - Biopolymeric film containing bioactive naphthoquinone (shikonin) in combined
      therapy of inflammatory destructive lesions in the buccal mucosa.
AB  - Clinical morphological efficiency of local application of a new biopolymeric film
      was studied. The film was based on methylcellulose derivatives and contained
      shikonin (preparation of plant origin) and its esters isolated from Lithospermum
      erythrorhizon L. cell culture. Combined therapy of 30 patients (34-72 years) with
      erosive ulcerative lichen planus and leukoplakia of the buccal mucosa was carried
      out. Local application of the new drug led to more rapid pain relief,
      epithelialization of the inflammatory destructive foci in the buccal mucosa, and
      reduced the intensity of morphological signs of lesions in the studied patient
      population. 

PMID- 24319757
TI  - Effects of thyroxin and mercazolyl on immunological parameters of blood
      lymphocytes and lymphoid organs.
AB  - Changes in the cellular and humoral immunity parameters were revealed in animals
      receiving thyroxin and mercazolyl per os for 2 weeks. Specific features of
      effects of the hormone and its inhibitor on the parameters of immune system were
      found. 

PMID- 24319758
TI  - Oxygen-dependent metabolism of intact and activated neutrophil granulocytes of
      the saliva.
AB  - The effects of phorbol-12-myristate-13-acetate on functional activity and
      viability of neutrophil granulocytes in the saliva of women at various phases of
      menstrual cycle were studied using NBT-test and method for detection of
      neutrophil traps in mucosa secretions. The activator increased the number of
      neutrophil traps and parameters of neutrophil NBT-test. 

PMID- 24319760
TI  - The incidence of breast tumor during experimental hyperthyroidism.
AB  - The incidence of breast tumor in inbred C3H-A mice (virgin female) from
      hyperthyroid, hypothyroid, and euthyroid control groups at week 44 of the
      experiment was 86.67, 30, and 62.5%, respectively. The percentage of metastatic
      lymph nodes in these groups was 65.9+/-16.7, 35.9+/-5.9, and 53.9+/-7.2%,
      respectively (p<0.005). It was shown that hyperthyroidism was associated with
      increased incidence and aggressiveness of breast tumor, while hypothyroidism was
      associated with lower incidence of breast tumor in comparison with the control. 

PMID- 24319759
TI  - Changes in proteasome chymotrypsin-like activity during the development of human
      mammary and thyroid carcinomas.
AB  - Changes in the proteasome chymotrypsin-like activity in mammary and thyroid
      carcinomas in comparison with the adjacent tissue were studied at stages T(1
      4)N(0-3)M(0) and T(2-3)N(0-1)M(0), respectively. The activities changed in a wave
      like manner over the course of mammary carcinoma growth in cases with and without
      metastases. The minimum increment of the activity in the tumor was recorded
      during the T(2)N(0) stage in the absence of local metastases. The increment of
      the activity reached the peak in N(1) tumors of the same size with metastases.
      The activities in the tumor and adjacent tissues virtually did not differ during
      the T(3-4)N(1-3) stages. The time course of proteasome activity changes in
      thyroid tumors of the studied stages was similar to that in mammary carcinoma.
      The results can be used for development of methods for evaluating the
      aggressiveness of mammary and thyroid tumors.

PMID- 24319761
TI  - Role of anaerobic bacteria in simian enteric diseases.
AB  - Screening of monkeys for anaerobic bacteria showed that the incidence of non
      spore-forming anaerobes was 2.0-2.5 times higher than that of clostridia. The
      overwhelming majority of isolated anaerobes were saprophytes and opportunistic
      bacteria. The incidence of C. perfringens was higher in monkeys with enteric
      infections of obscure etiology and dead from these diseases than in healthy
      animals (48.2 vs. 36.8%). 

PMID- 24319762
TI  - The use of nanocomposite coatings with various physicochemical properties in
      tissue engineering.
AB  - We studied the effect of nanocomposite coatings with various physicochemical
      properties on the structural and functional properties (adhesion potential,
      phenotype, gene expression) of mesenchymal stem cells. Of all tested nanocoatings
      (Al2O3, ZrO2, Ta2O5), oxide coating Al2O3 enriched in vitro monolayer bone marrow
      cell culture with cells carrying mesenchymal stem cells phenotype markers and
      stimulated expression of ido gene, which can confer new therapeutic potencies to
      these cells and extend their application in clinical practice. 

PMID- 24319763
TI  - Estimation of mutagenic effect and modifications of mitosis by silver
      nanoparticles.
AB  - We analyzed mutagenic and mitosis-modifying effects of silver nanoparticles
      (Allium test). Chromosome aberrations and laggings and micronuclei were
      simultaneously registered in the same sample. Mitotic and phase indexes were
      calculated. No mutagenic effects were detected after treatment with silver
      nanoparticles in doses of 1.0, 2.5, 5.0, and 50 mg/liter. Silver nanoparticles in
      a concentration of 50 mg/liter significantly increased the mitotic index.
      Nanoparticles in a dose of 5 mg/liter induced slight, but significant increase in
      mitotic index, but did not affect the ratio of phase indexes. Exposure to silver
      nanoparticles in concentrations of 1.0 and 2.5 mg/liter was not followed by
      modification of mitosis. 

PMID- 24319764
TI  - Comparative analysis of the kinetics of DNA synthesis after exposure during
      different phases of the cell cycle S period.
AB  - The kinetics of DNA synthesis in the mitotic cycle of mouse corneal epithelial
      cells was studied after a single gamma-irradiation of cells in a dose of 4 Gy at
      different S-phase points. Normally, corneal epitheliocyte S phase consists of S1
      and S2 phases separated by an interval during which no DNA is synthesized. The
      duration of each phase was lengthened after single irradiation due to reparation
      of injuries in the cells at the expense of the time normally occupied by g1
      period of the mitotic cycle. The first event during reparation is excision of
      damaged complex from the DNA molecule; this complex consists of labeled daughter
      fragment and matrix site of DNA chain that was used for the synthesis of the
      daughter fragment. Presumably, the entire reparation process in the cell consists
      of two stages: "reparative" synthesis and "additional" synthesis. The reparative
      synthesis, in turn, includes two stages: de novo synthesis of matrix fragment in
      the DNA chain at the site of the gap formation and de novo synthesis of the
      daughter fragment after the synthesis of the new matrix fragment is over. 

PMID- 24319765
TI  - Morphometric evaluation of vascularization of hepatic focal nodular hyperplasia.
AB  - Comparative morphometric evaluation of the quantitative characteristics of
      vessels in hepatic focal nodular hyperplasia tissue was carried out on
      preparations stained with hematoxylin and eosin and by immunohistochemical
      detection of CD34 and CD105. Analysis of histological preparations stained with
      hematoxylin and eosin allowed the most ample characterization.
      Immunohistochemical detection of CD34 promoted better visualization of
      endotheliocytes, but just some sinusoids in the preparations were labeled.
      Expression of CD105 visualized the active endothelial cells and hence, helped to
      evaluate neoangiogenesis. 

PMID- 24319767
TI  - Morphological and immunohistochemical changes in the liver in coarctation of the
      aorta during compensation and decompensation stages.
AB  - Compensated coarctation of the aorta is accompanied by a decrease in the tone of
      hepatic vessels, thinning of the vascular walls, and moderate expression of alpha
      SMA. Bundles of intimal muscles, myoelastic sphincters, and polyp-like pads form
      in the arteries; the muscle rolls in the efferent veins degenerate. Hepatocyte
      changes are presented by focal involvement of the organelles. Decompensated
      coarctation is characterized by more pronounced atrophy of hepatic vascular walls
      and regulatory structures. The expression of alpha-SMA in the arteries increases,
      sclerosis develops, and signs of CD34 expression in the sinusoids and
      perisinusoidal fibrosis emerge. All these shifts are associated with coarse
      ultrastructural changes in hepatocytes. 

PMID- 24319766
TI  - Expression of mRNA of apolipoprotein E, apolipoprotein A-IV, and matricellular
      proteins in the myocardium and intensity of fibroplastic processes during
      experimental hypercholesterolemia.
AB  - The expression of mRNA of matricellular proteins (osteopontin, and lumican),
      apolipoproteins E and A-IV, and microsomal triglyceride transfer protein, and the
      intensity of fibroplastic processes were studied in the myocardium of rats during
      experimental chronic hypercholesterolemia. We have found that the development of
      chronic hypercholesterolemia was followed by an increase in volume density of
      interstitial connective tissue in the myocardium reflecting the activation of
      fibroplastic processes. A slight positive correlation was observed between the
      connective tissue density in the myocardium and expression of osteopontin mRNA
      (r=0.408) and lumican mRNA (r=0.470). Myocardium remodeling during
      hypercholesterolemia is realized against the background of increased expression
      of apolipoproteins E and A-IV mRNA and microsomal triglyceride transfer protein
      mRNA involved in transport and metabolism of lipoproteins in several tissues and
      probably play a pivotal role in the regulation of lipoprotein transport and
      metabolism in the myocardium. We concluded that the increase in the expression of
      apolipoproteins (E and A-IV) and microsomal triglyceride transfer protein play
      adaptive and compensatory role and is related to the increase in lipoprotein
      utilization by macrophages. 

PMID- 24319768
TI  - Role of lipid infiltration of hepatocytes in the morphogenesis of chronic
      hepatitis C.
AB  - Immunohistochemical and PCR analysis of the structure of lipid-containing
      hepatocytes and replication of chronic hepatitis C viral particles revealed no
      positive correlation between the presence of HCV RNA in blood specimens, number
      of infected hepatocytes (by expression of HCV NS3Ag) with clinical biochemical
      parameters and intensity of structural changes in biopsy specimens. Small
      vesicular subcytolemmal lipid infiltration of hepatocytes was detected,
      presumably associated with hepatitis C virus replication phase. Characteristic
      subcytolemmal location of the lipid droplets can reflect their involvement in
      virus transport from the cell and indicate a virus-induced nature of lipid
      metabolism disorders. 

PMID- 24319769
TI  - Effects of composition of biocomposite materials implanted into hole defects of
      the metaphysis on the reparative regeneration and mineralization of bone tissue.
AB  - We carried out a comparative analysis of morphological pattern and element
      composition of regenerated bone tissue forming in the metaphysis defects after
      substitution of these defects with calcium phosphate substance containing low
      molecular non-collagen bone proteins with various affinities to ion exchangers.
      We have found that regenerated tissue in the defects grew from the edges to the
      center and its element composition depended on the maturity of newly formed bone
      tissue. Implantation material containing non-collagen bone proteins with various
      affinities to ion exchangers induced no significant changes in the content of
      analyzed elements of bone tissue around the defect. The content of analyzed
      elements in the areas distant from the defect area did not change during the
      experiment. 

PMID- 24319770
TI  - Soft contact lenses as prospective transport systems for ophthalmology.
AB  - The time course of drug adsorption and desorption, exposure of soft contact
      lenses in a drug solution needed for maximum saturation, and the duration of lens
      wearing during which the drug was transported from the lens and exhibited its
      therapeutic activity were studied. The possibility of using computer simulation
      for the choice of material, carrier for the drug (myramistin hydrochloride), was
      evaluated. Due to use of this method, the volume of experimental studies could be
      reduced and the data systematized. 

PMID- 24319772
TI  - Detection of drugs in lifted cyanoacrylate-developed latent fingermarks using two
      laser desorption/ionisation mass spectrometric methods.
AB  - This paper describes a method for lifting cyanoacrylate (CNA)-developed latent
      fingermarks from a glass surface and the detection of five drugs in lifted marks
      from fingers that had been in contact with the drugs, using Surface Assisted
      Laser Desorption Ionisation Time of Flight Mass Spectrometry (SALDI-TOF-MS) or
      Matrix Assisted Laser Desorption Ionisation TOF-MS (MALDI-TOF-MS). Two drugs of
      abuse (cocaine and methadone) and three therapeutic drugs (aspirin, paracetamol
      and caffeine) were used as contact residues. Latent fingermarks spiked with the
      drugs were subjected to CNA fuming followed by dusting with ARRO SupraNanoTM MS
      black magnetic powder (SALDI-TOF-MS) or 2,5-dihydroxybenzoic acid (DHB) (MALDI
      TOF-MS). The dusted mark was then exposed to solvent vapour before lifting with a
      commercial fingerprint lifting tape following established procedures. The
      presence of the drugs was then confirmed by direct analysis on the tape without
      further processing using SALDI- or MALDI-TOF-MS. The black magnetic fingerprint
      powder provided visual enhancement of the CNA-fingermark while no visual
      enhancement was observed for marks dusted with DHB powder. Similar [M + H](+)
      peaks for all the drug analytes were observed for both methods along with some
      sodium and potassium adducts for SALDI-MS and some major fragment ions but the
      SALDI signals were generally more intense. Simple exposure to acetone vapour of
      the CNA-developed marks enabled their effective transfer onto the tape which was
      crucial for subsequent MS detection of the analytes.

PMID- 24319773
TI  - A multidisciplinary approach to managing invasive fungal disease. Introduction
      and aims.

PMID- 24319774
TI  - A multidisciplinary approach to managing invasive fungal disease. Preface.

PMID- 24319775
TI  - River blindness elimination in Columbia.

PMID- 24319777
TI  - The dual mucus defence.

PMID- 24319780
TI  - The Editor-in-Chief responds.

PMID- 24319778
TI  - Immunological functions of the  neuropilins and plexins as receptors  for
      semaphorins.
AB  - Semaphorins were originally identified as axon-guidance molecules that function
      during neuronal development. However, cumulative evidence indicates that
      semaphorins also participate in immune responses, both physiological and
      pathological, and they are now considered to be potential diagnostic and/or
      therapeutic targets for a range of diseases. The primary receptors for
      semaphorins are neuropilins and plexins, which have cell type-specific patterns
      of expression and are involved in multiple signalling responses. In this Review,
      we focus on the roles of neuropilin 1 (NRP1) and plexins in the regulation of the
      immune system, and we summarize recent advances in our understanding of their
      pathological implications.

PMID- 24319781
TI  - Social media and physician learning: is it all twitter?

PMID- 24319782
TI  - Infectious disease/CDC update. Vital signs: Listeria illnesses, deaths, and
      outbreaks-United States, 2009-2011.

PMID- 24319783
TI  - Retraction.

PMID- 24319779
TI  - Immune regulation by atypical  chemokine receptors.
AB  - Chemokines have fundamental roles in regulating immune and inflammatory
      responses, primarily through their control of leukocyte migration and
      localization. The biological functions of chemokines are typically mediated by
      signalling through G protein-coupled chemokine receptors, but chemokines are also
      bound by a small family of atypical chemokine receptors (ACKRs), the members of
      which are unified by their inability to initiate classical signalling pathways
      after ligand binding. These ACKRs are emerging as crucial regulatory components
      of chemokine networks in a wide range of developmental, physiological and
      pathological contexts. In this Review, we discuss the biochemical and
      immunological properties of ACKRs and the potential unifying themes in this
      family, and we highlight recent studies that identify novel roles for these
      molecules in development , homeostasis, inflammatory disease, infection and
      cancer.

PMID- 24319785
TI  - Monthly report on dracunculiasis cases, January-September 2013.

PMID- 24319784
TI  - Validation of maternal and neonatal tetanus elimination in Cameroon, 2012.

PMID- 24319786
TI  - Donald Stewart Malcolm.

PMID- 24319787
TI  - Thakshan Lal Udayamitta Fernando.

PMID- 24319788
TI  - Grants for States for construction or acquisition of State homes. Final rule.
AB  - This rule adopts as final, without change, an interim final rule amending the
      Department of Veterans Affairs (VA) regulations governing prioritization of State
      applications for VA grants for the construction or acquisition of State home
      facilities that furnish domiciliary, nursing home, or adult day health care to
      veterans. As amended, the regulation gives preference to State applications that
      would use grant funds solely or primarily (under certain circumstances) to remedy
      cited life or safety deficiencies. This rulemaking also makes certain necessary
      technical amendments to regulations governing State home grants.

PMID- 24319789
TI  - Progress towards poliomyelitis eradication in Pakistan, January 2012- September
      2013.

PMID- 24319790
TI  - [Lower G.I./colon and rectum cancer].

PMID- 24319791
TI  - [I. Molecular targeted therapy for unresectable wild type K-ras recurrent colon
      cancer].

PMID- 24319792
TI  - [II. Which is the better choice for second- line treatment?; BEV or anti-EGFR
      after BEV treatment in patients with unresectable wild type K-ras colon cancer].

PMID- 24319793
TI  - [III.Is adjuvant chemotherapy effective for unresectable metastatic liver
      cancer?].

PMID- 24319794
TI  - [Economic crisis does not skip veterinarians].

PMID- 24319795
TI  - [Buying cheap is expensive].

PMID- 24319796
TI  - [Surveillance].

PMID- 24319797
TI  - [Results from a 5 year manure research study on coccidiosis in calves].

PMID- 24319798
TI  - [Containment of the Schmallenbergvirus].

PMID- 24319799
TI  - [CPSE test to screen for benign prostate hyperplasia in the dog: insane?].

PMID- 24319800
TI  - [Better diagnosis for airway infections in calves].

PMID- 24319801
TI  - [Sick because of conflict at work].

PMID- 24319803
TI  - [Intervision as long term vision].

PMID- 24319802
TI  - [Is dehorning really so standard?].

PMID- 24319804
TI  - [Welfare large domestic animals between morale and biology].

PMID- 24319805
TI  - [Judging pain in pets is serious].

PMID- 24319806
TI  - The best relevant articles in pediatric hospital medicine.

PMID- 24319807
TI  - The challenge of pediatric hospital medicine research.

PMID- 24319808
TI  - Traditional measures of hospital utilization may not accurately reflect dynamic
      patient demand: findings from a children's hospital.
AB  - OBJECTIVES: Hospital crowding adversely affects access to emergent and elective
      care, quality and safety, patient and staff satisfaction, and trainee education.
      Reliable and valid measurements are crucial to operational planning and
      improvement, but traditional measures of hospital utilization may not accurately
      describe dynamic demand at hospitals. The goal of this study was to determine how
      effectively traditional measures express demand for hospital services and to
      describe the dynamic nature of patient flow in children's hospitals compared with
      alternative measures. METHODS: This was a retrospective administrative data
      review conducted at an urban, tertiary care children's hospital. A total of 28045
      inpatients (22310 from fiscal year 2008 and 5735 from 2 months in the fall of
      2009 during the H1N1 influenza surge [October 16, 2009-November 18, 2009]) were
      reviewed. Admission-discharge-transfer data were abstracted from a total of 14
      months (1 fiscal year and a separate 2 months including an influenza surge).
      Hourly hospital census and occupancy were determined. Measures of mean and median
      length of stay (LOS) were compared. Turnover was calculated by summing
      admissions, discharges, and interunit transfers. Coefficient of variation
      (SD/mean) was used to describe variation. RESULTS: Midnight occupancy was
      generally closer to minimum occupancy than peak. Peak was usually between 10 AM
      and 12 PM and was a mean of 40/% points higher than midnight (but as large as 13%
      points). Median LOS was 58% shorter than average LOS. There was a high level of
      turnover, and patient-days did not express the wide variation in how demand was
      generated by day of week. CONCLUSIONS: Traditional metrics for hospital
      utilization do not accurately express the true extent and dynamic nature of
      patient flow and inpatient demand at a children's hospital. Hospitals and
      government regulatory agencies should consider additional means of measuring
      utilization to accurately determine demand, including its variation, and thus
      assist in budgeting, staffing, and capacity planning.

PMID- 24319809
TI  - Hospitalist and nonhospitalist adherence to evidence-based quality metrics for
      bronchiolitis.
AB  - OBJECTIVES: Hospitalists are a new subgroup of pediatricians. However, data
      comparing quality of care between hospitalists and nonhospitalists are limited.
      Bronchiolitis, a common cause of pediatric hospital admission, is an appropriate
      condition for evaluating inpatient quality of care. The goal of this study was to
      identify quality indicators for the evaluation and treatment of children
      hospitalized with bronchiolitis based on the 2006 American Academy of Pediatrics
      guidelines and to assess differences in adherence rates to these indicators
      between hospitalist and nonhospitalist pediatricians. METHODS: This was a
      retrospective chart review of children admitted to 2 academic centers in 2007 and
      2008. Reviewers selected charts with a discharge diagnosis of bronchiolitis and
      collected data on evaluation, treatment, length of stay, readmission, and adverse
      outcomes. RESULTS: Reviewers analyzed 713 charts. In children without objective
      response to bronchodilator therapy, hospitalists and nonhospitalists discontinued
      albuterol and racemic epinephrine similarly. Hospitalists discontinued
      unnecessary systemic corticosteroid therapy (75.0% vs 42.4%; P= .001) and
      antibiotic therapy (71.0% vs 48.6%; P= .007) more frequently than
      nonhospitalists. CONCLUSIONS: These data suggest hospitalists better adhere to
      selected portions of the American Academy of Pediatrics bronchiolitis guidelines,
      thus providing higher quality of care. Quality indicators used in this study can
      distinguish physician performance in the inpatient management of bronchiolitis.

PMID- 24319810
TI  - Admission screening for secondhand tobacco smoke exposure.
AB  - OBJECTIVES: Secondhand smoke (SHS) exposure is an important and preventable cause
      of mortality and morbidity among children; hospitalization represents a sentinel
      event that may offer opportunities for intervention. The goal of this study was
      to determine the frequency and validity of SHS exposure screenings by emergency
      department (ED) providers, residents, and nurses. METHODS: A total of 140
      inpatient pediatric families consented to a salivary cotinine measurement, in
      person SHS exposure interview, and chart review to assess ED provider, pediatric
      resident, and nurse SHS exposure screenings and documentation validity. RESULTS:
      ED providers documented screening for SHS exposure 46% of the time, pediatric
      residents 42% of the time, and nurses 79% of the time. ED providers, pediatric
      residents, and nurses reported 18%, 38%, and 12% of patients exposed to SHS,
      respectively, whereas 46% of patients were identified as smoke-exposed according
      to cotinine level and/or parent report. Those with SHS exposure outside the home
      were least likely to be identified as exposed. CONCLUSIONS: The majority of smoke
      exposed children were not identified as exposed based on documentation of
      admission screenings. Future research is important to identify accurate and
      efficient methods of screening for and identifying SHS exposure among children
      admitted to the hospital.

PMID- 24319811
TI  - Perceptions of physician bedside handoff with nurse and family involvement.
AB  - OBJECTIVE: Physician-to-physician handoffs have been identified as a high-risk
      area of patient care. Few data exist to support any specific handoff process as
      being superior. We developed a handoff process entitled physician bedside handoff
      (PBH), which is unique for allowing all stakeholders, including the parents of
      patients, to be involved in the handoff at the bedside. Our goal was to compare
      stakeholder perceptions of PBH with traditional physician handoff and to learn
      which factors stakeholders believe are important for improving handoffs in
      general. METHODS: A convenience sample of 34 stakeholders (including attending
      physicians, residents, nurses, patient care attendants, patient parents, and
      medical students) participated in 1 of 3 group level assessments IGLAs), a
      participatory method in which valid data are generated regarding an issue of
      importance through an interactive and collaborative process. RESULTS: In
      comparing PBH and traditional handoffs, participants uniformly perceived that
      both processes have value and that neither is superior in all cases; individual
      circumstances and parental preference should dictate which is used. Participation
      of all stakeholders was identified as being essential in improving handoffs in
      general. Other themes included that handoffs should occur in both verbal and
      written formats, and that providers and learners, specifcally medical students
      and residents, should be comfortable with both types of handoffs. CONCLUSIONS:
      Participants identified that including all stakeholders is essential to improve
      handoffs, that PBH is not superior to traditional handoffs, and that both
      processes have value. Further research should be conducted to determine if
      including all stakeholders in the handoff process results in improved quality of
      care and safety.

PMID- 24319812
TI  - Hiring pediatric hospitalists: the process matters.

PMID- 24319813
TI  - Is it time to change how I diagnose, treat, and manage young children with
      urinary tract infections?

PMID- 24319814
TI  - All that wheezes....

PMID- 24319816
TI  - Standing up for the ethics of health care.

PMID- 24319815
TI  - From intensive to primary care: bridging the gap for better medicine.

PMID- 24319817
TI  - Tea room.

PMID- 24319818
TI  - Professional accountability.

PMID- 24319819
TI  - Worrying signs from an immature government.

PMID- 24319820
TI  - Parting thoughts.

PMID- 24319821
TI  - Evidence-based practice readiness of ASORN members.
AB  - Due to the importance of evidence-based practice and its impact on patient
      outcomes, a research study was conducted in early 2013 soliciting participation
      of ASORN members. Findings indicate the collegiality and curiosity of nurses, who
      identify a gap in practice due to lack of knowledge/skills and organizational
      barriers. Since nurses value EBP and research, as noted in study findings and
      ASORN Board of Directors support, efforts to advance the art and science of
      ophthalmic nursing will continue in the future.

PMID- 24319822
TI  - Handle avastin and lucentis with care.

PMID- 24319824
TI  - ASORN recommended practice: use of multi-dose medications.

PMID- 24319823
TI  - Flash sterilization conversion to complete sterilization process.

PMID- 24319825
TI  - Subperiosteal hematoma of the orbit.

PMID- 24319826
TI  - Computer vision syndrome.

PMID- 24319827
TI  - Benefits of certification for the ophthalmic registered nurse.

PMID- 24319829
TI  - Top articles in pediatric hospital medicine.

PMID- 24319828
TI  - Imelda Kelly, RN, CRNO.

PMID- 24319830
TI  - Length of stay and readmission among late preterm infants: an instrumental
      variable approach.
AB  - OBJECTIVE: Evidence to guide safe discharge for late preterm infants (34-36
      weeks' gestation) is lacking. Previous studies have demonstrated the increased
      risk of neonatal readmission for these infants compared with those born at term
      (> or =37 weeks' gestation). The purpose of this study was to estimate the effect
      of length of stay (LOS) on 7-day readmissions in this population. METHODS: This
      was a retrospective study using hospital discharge data linked with vital records
      for late preterm infants delivered vaginally in California from 1993 to 2005.
      Exclusion criteria included complications likely requiring neonatal intensive
      care. The effect of LOS was assessed by using birth hour as an instrumental
      variable to account for unmeasured confounding. By using a matching algorithm, we
      created pairs of infants with different LOS based on birth hour but otherwise
      matched on known confounders for readmission risk, including birth year,
      hospital, and clinical and demographic covariates such as gestational age, birth
      weight, race, and insurance. RESULTS: We produced 80600 matched pairs of infants
      with different LOS based on birth hour. In 122 pairs, both infants were
      readmitted within 7 days, and in 75362 pairs, neither infant was readmitted. Of
      the remaining 5116 matched pairs in which only 1 infant was readmitted, 2456
      infants with long LOS and 2660 infants with short LOS were readmitted. We found
      no evidence that longer LOS reduces the odds of readmission (1-sided P value =
      .99). CONCLUSIONS: By using an instrumental variable approach and matching
      algorithm, longer LOS was not associated with decreased readmission within 7 days
      of discharge for these late preterm infants.

PMID- 24319831
TI  - Are there risks associated with empiric acid suppression treatment of infants and
      children suspected of having gastroesophageal reflux disease?
AB  - BACKGROUND: It has become common practice to empirically treat infants and
      children who have suspected gastroesophageal reflux disease by using acid
      suppressive medications. However, evidence to support the effectiveness of these
      medications in the pediatric population is limited. With multiple studies in
      adult patients indicating increased risk of infection, we reviewed the literature
      to determine the association between acid-suppressive medications and serious
      adverse effects in infants and children. METHODS: We conducted a PubMed search on
      the adverse effects of H2 antagonists and proton pump inhibitors in pediatric
      patients. The studies selected were original research and systematic reviews with
      control groups and study objectives evaluating the relationship between acid
      suppressive medications and serious adverse effects (namely, infections).
      RESULTS: Fourteen studies met our inclusion criteria. The majority of studies
      found a significant association between acid-suppressive medications and the risk
      of necrotizing enterocolitis, sepsis/bacteremia, pneumonia, and gastrointestinal
      infections in infants and children. CONCLUSIONS: Given the questionable efficacy
      of H2 antagonists and proton pump inhibitors and the growing evidence of
      increased risk of serious infections, acid-suppressive medications should be used
      cautiously in infants and children suspected of having gastroesophageal reflux
      disease.

PMID- 24319832
TI  - Relationship between caloric intake and length of hospital stay for infants with
      bronchiolitis.
AB  - OBJECTIVE: Poor oral intake is a common presenting symptom among infants
      hospitalized with bronchiolitis. The prevalence, degree, and duration of
      iminished caloric intake in these infants have not been studied. Our goal was to
      determine the daily caloric intake among infants admitted with bronchiolitis and
      to evaluate the relationship between early hospital caloric intake and length of
      stay (LOS). METHODS: We conducted a retrospective chart review of infants aged <1
      year admitted to Children's Hospital of Wisconsin with bronchiolitis who were
      placed in the bronchiolitis treatment protocol during the 2004-2005 season.
      Patient-, disease-, respiratory-, and nutrition-specific data were abstracted.
      RESULTS: A total of 273 patients with bronchiolitis were admitted between
      November 1, 2004, and April 15, 2005; placed on the bronchiolitis protocol; and
      included in the study. Median caloric intake was diminished on day 1 (53 kcal/kg
      per day) and day 2 (64 kcal/kg per day). Caloric intake was slower to normalize
      in infants with progressively longer LOS, and a slower rate of increase from day
      1 to day 2 was significantly correlated with longer LOS (r= -0.18; P= .002).
      Subgroup analysis revealed significant correlations between hospital day 2
      caloric intake and LOS in formula-fed infants, breastfed infants, infants aged
      <183 days, and infants aged > or =183 days. CONCLUSIONS: Caloric intake was
      diminished in the early course of hospitalization for infants who had
      bronchiolitis and slowest to normalize in infants with the longest LOS.
      Interventions aimed at decreasing LOS among infants admitted with bronchiolitis
      should consider the potential significance of nutrition for severely affected
      infants with this condition.

PMID- 24319833
TI  - A time-motion study of inpatient rounds using a family-centered rounds model.
AB  - OBJECTIVE: Family-centered rounds (FCR) have become increasingly prevalent in
      pediatric hospital settings. The objective of our study was to describe time use
      and discrete events during pediatric inpatient rounds by using a FCR model.
      METHODS: We conducted a prospective observational study at Children's National
      Medical Center between September 2010 and February 2011. Investigators directly
      observed rounds on hospitalist and neurology services. Events were timed, and key
      features were recorded by using a Microsoft Access-based program. Associations
      with increased time spent during rounds were determined by using regression
      analyses. RESULTS: One hundred fifty-nine rounding encounters were observed.
      Rounds lasted 7.9 minutes on average per patient. An average of 1.3 minutes was
      spent between patients during rounds. Eighty-six (54%) encounters occurred
      outside the patient's room, 3% of the time because of the family's request.
      Infectious isolation was associated with rounds occurring outside the room
      (P<.0001). Participation of the parent, location of rounds inside or outside the
      patient's room, most teaching behaviors, and interruptions were not significantly
      associated with increased time spent during rounds. Teaching physical examination
      techniques by allowing multiple trainees to examine the patient was associated
      with increased rounding time (P= .02). CONCLUSIONS: The majority of rounds
      occurred outside the patient's room, yet rarely at the parent's request. Patients
      on infectious isolation were more likely to have rounds occur outside the
      patient's room. Neither parental participation nor most teaching behaviors were
      associated with increased time spent on rounds. These findings will enrich the
      evidence base needed to establish FCR best practices.

PMID- 24319834
TI  - A preliminary screening instrument for early detection of medical child abuse.
AB  - OBJECTIVE: The goal of this research was to develop a screening instrument for
      early identification among hospitalized children of medical child abuse (MCA).
      METHODS: We developed a preliminary screening instrument for the early
      identification of MCA. Items were chosen based on published characteristics of
      MCA, including caregiver, patient, and illness information. Each item in the
      instrument was scored with 1 point if positive. This instrument was tested by
      reviewing the hospital charts of child protective services-confirmed MCA patients
      and comparing the results with charts of children with admissions for apnea,
      vomiting/diarrhea, and seizures who were not diagnosed with MCA. Nineteen cases
      and 389 controls were used for analysis. We used receiver operating
      characteristic curves, starting with items most highly associated with MCA in our
      sample. Predictive values and strengths of association were assessed by using
      chi2 and Fisher's exact tests, as appropriate. RESULTS: From an initial 46
      questions, we determined that 26 items showed a statistically significant
      difference between cases and control patients. From these, an instrument with 15
      items maximized the area under the receiver operating characteristic curve, and a
      score of > or =4 had a sensitivity of 0.947 and a specificity of 0.956 (P<.05) in
      detecting MCA. CONCLUSIONS: This chart review screening instrument identified
      differences in characteristics of children, caregivers, and illness during
      hospitalization that may allow for earlier detection of MCA and referral for
      further assessment to the multidisciplinary team.

PMID- 24319835
TI  - A quality improvement project to improve compliance with the joint commission
      children's asthma care-3 measure.
AB  - BACKGROUND AND OBJECTIVE: Since the initiation of the Children's Asthma Care
      (CAC) core measures in 2008, hospitals have struggled to achieve a high rate of
      compliance with the CAC-3 measure of the Home Management Plan of Care (HMPC). At
      inception of this project in 2009, the national average was 65% compliance, which
      has now increased to 80%. These rates are below the Hospital Corporation of
      America's goal of 90% compliance. Our objective was to identify potential
      pitfalls that interfere with compliance on CAC-3 at our institution and to devise
      solutions to increase compliance to >90%. METHODS: Inpatient pediatric patients
      at a community teaching hospital in a predominantly rural state were included in
      our interrupted time-series quality improvement project from 2008 to 2011.
      Patients were between 2 and 17 years of age with an International Classification
      of Diseases, Ninth Revision (ICD-9), primary diagnosis code of asthma at time of
      discharge. We identified potential stumbling blocks that interfered with
      compliance of CAC measures and then implemented repeated Plan-Do-Study-Act (PDSA)
      cycles to improve processes, including redesign of the HMPC form, education, and
      electronic documentation tied to the discharge medication reconciliation form,
      which is also required by The Joint Commission. RESULTS: We started with an
      average quarterly compliance of 43% with CAC-3 before our PDSA cycles. We have
      improved our compliance after the 2 PDSA cycles to an average of 97%.
      CONCLUSIONS: By linking the HMPC form to the discharge medication reconciliation
      form, we were able to achieve and maintain >90% compliance with CAC-3.

PMID- 24319836
TI  - Successful implementation of a referral-based academic pediatric hospitalist
      service.
AB  - OBJECTIVE: St Louis Children's Hospital (SLCH) developed Service for Hospital
      Admissions by Referring Physicians (SHARP) in January 2008 as an inpatient
      referral service for pediatricians who previously admitted their own patients. We
      hypothesized that use of SHARP would make hospitalization more efficient and cost
      effective compared with the general pediatric medicine (GM) service. METHODS:
      Admission volumes, diagnoses, length of stay (LOS), costs, and physician billing
      data were abstracted from SLCH information systems and the Pediatric Health
      Information System database. We compared admissions for SHARP and GM from January
      2008 through June 2010. RESULTS: SHARP had lower LOS and costs versus GM, with no
      change in 7-day readmission rate. Median LOS was 2 days for SHARP and 3 days for
      GM (P<.001). Median hospital cost per patient was $2719 for SHARP and $3062 for
      GM (P<.001). Over the study period, the admission rate increased 37% and daily
      patient encounters increased 39%. Physician billing revenue increased 25% in the
      first 6 months, then continued to increase steadily. Total physicians and
      geographic referral area using SHARP increased, and referring physician
      satisfaction was high. CONCLUSIONS: SHARP approaches financial independence and
      provides a cost savings to SLCH. LOS decreased by a statistically significant
      amount compared with GM with no change in readmission rate. Referring physician
      satisfaction was high, likely allowing for growth in referrals to SLCH. SHARP
      hospitalists' collaboration with referring physicians, ensuring excellent follow
      up, provides decreased duration of hospitalization and resource utilization. Our
      availability throughout the day to reassess patients increases efficiency. We
      project that we must average 12.6 daily encounters to be financially independent.

PMID- 24319837
TI  - A qualitative description of the development and evaluation of our voice, a
      health promotion magazine created by pediatric patients for hospitalized
      pediatric patients.
AB  - OBJECTIVES: To facilitate a peer-developed health promotion magazine that
      provides health education and engages hospitalized pediatric patients during a
      hospital admission. To evaluate patient satisfaction with the content and layout
      of the magazine and its impact on patients' attitudes toward healthy living.
      METHODS: A pediatric resident-led multidisciplinary team collaborated with the
      Children's Council at The Hospital for Sick Children to create a health promotion
      magazine for inpatients. Articles included a scavenger hunt, healthy recipes,
      physical activities, hospital staff interviews, and patient stories. Patients 7
      to 18 years of age admitted to Pediatric Medicine or Respirology were invited to
      read the magazine and complete a questionnaire 24 hours later on their
      satisfaction with the magazine and their attitudes regarding healthy living.
      RESULTS: Thirty-seven patients received a copy of the magazine, and 24 patients
      completed the questionnaire (mean 13.4 years, 54% female, 25% overweight/obese).
      Eleven of 24 (46%) read the entire magazine, and 19 of 23 (83%) reported
      learning. The exercises, recipes, and patient stories were most liked. Ten of 24
      (42%) participants performed the exercises; the most common reason for not trying
      an exercise was pain. After reading the magazine, 15 of 24 (65%) patients
      reported that they will try to be more active, and 11 of 23 (48%) reported that
      they will try to eat more fruits and vegetables. Eighty-three percent were
      interested in a future edition. CONCLUSIONS: A health promotion magazine created
      by patients for patients changed patient-reported attitudes about healthy living.
      Peer-led interventions in the inpatient setting may be an important opportunity
      to promote healthy lifestyles and require further study.

PMID- 24319838
TI  - Challenging cases: how do we intervene with pediatric med/psych issues?

PMID- 24319839
TI  - One approach to facial swelling: tooth or fiction.

PMID- 24319840
TI  - In defense of my lazy and entitled generation: an open letter to my elders.

PMID- 24319841
TI  - What's in a name?

PMID- 24319842
TI  - Praise the bridge that carried you over.

PMID- 24319843
TI  - Postpartum depression among Thai women: a national survey.
AB  - OBJECTIVE: To determine prevalence rates and associated factors of postpartum
      depression among Thai women. MATERIAL AND METHOD: A cross- sectional national
      survey and descriptive study of 1, 731 women was done. The participants were
      required to complete a self-administered questionnaire consisting of inquiries on
      social demographic data, obstetric data, maternal and child health, stressful
      life events within the past 12 months, support system, and 10 items of the
      Edinburgh Postnatal Depression Scale-Thai version. The prevalence and associated
      factors of postpartum depression (PPD) were evaluated RESULTS: The prevalence of
      PPD among Thai women was 8.4%. In the multivariate model, the factors
      independently associated with PPD included maternal health, marital conflict,
      economic burden, stressful life events, and previous depression. Support from
      their families was a protective factor from postpartum depression. CONCLUSION:
      The present study found that PPD was 8.4%. Screening for depression in women
      after giving birth should be taken into consideration. Public health intervention
      targeted for population with PPD may be needed to reduce the prevalence of PPD
      and its impacts.

PMID- 24319844
TI  - Trend in mode of delivery in Rajavithi Hospital: a ten-year analysis (2002-2011).
AB  - OBJECTIVE: To create trends in mode of delivery both public and private service
      at Rajavithi Hospital. MATERIAL AND METHOD: The medical records of singleton
      pregnant women delivered between January 1, 2002 and December 31, 2011 were
      retrospectively analyzed for mode of delivery, indication of operative
      obstetrics, and modality of services (public and private service). RESULTS:
      During the study period, total singleton deliveries gradually decreased from
      9,418 to 6,023 while the spontaneous vaginal delivery rate fluctuated, and the
      cesarean delivery rate increased from 25.48% to 34.70%. Vaginal operative
      deliveries steadily declined such as, forceps extraction 3.83% to 0.95%, vacuum
      extraction, 1.72% to 0.85%, and vaginal breech delivery 0.92 to 0.28%.
      CONCLUSION: The cesarean delivery rate increased in contrast with the decline of
      the vaginal operative delivery rate.

PMID- 24319845
TI  - Factors determining the appropriateness of ceftriaxone usage at the emergency
      room of a university hospital in Thailand.
AB  - BACKGROUND: Ceftriaxone is one of the most common empirical antibiotics
      prescribed at emergency rooms in Thailand. Inappropriate prescriptions of
      antibiotics have been frequently reported. The authors aimed to study factors
      that determine the appropriateness ofceftriaxone usage at an emergency room ofa
      university hospital in Thailand. MATERIAL AND METHOD: A cross-sectional study was
      conducted among patients with age of> 15 years old who received ceftriaxone as
      empirical treatment at the emergency room between April 1 and May 31, 2010.
      Appropriateness ofceftriaxone usage was considered according to local
      recommendations and current published guidelines. RESULTS: During the 2-months
      period, 278 patients for whom ceftriaxone was prescribed were included in the
      analysis. Of these, 109 (39.2%) were men and a median (interquartile range; IQR)
      age of 62.2 (45.2-75.7) years. Ceftriaxone usage was considered appropriate in
      162 (58.3%) cases. By multiple logistic regression, female gender [odds ratio
      (OR) 1.96, 95% confidence interval (CI) 1.03-3. 70], fever (OR 3.12, 95% CI 1.3
      6.11), had signs and symptoms of infections (OR 2.92, 95% CI 1.37-6.28), and
      suspicion of sepsis (OR 7.90, 95% CI 3.67-17.07), were associated with
      appropriateness of ceftriaxone usage, while diagnosis of gastrointestinal tract
      infection was associated with inappropriate ceftriaxone usage (OR 0.20, 95% CI
      0.05-0.77). CONCLUSION: Proportion of appropriate use of ceftriaxone is fair. As
      assessed by established criteria, clinical suspicion of infection was associated
      with appropriateness of ceftriaxone usage for empirical treatment in an emergency
      room setting. Interventions to improve appropriateness of ceftriaxone
      prescription should focus on these factors.

PMID- 24319846
TI  - Hospital tuberculosis control activities and treatment success in Thailand during
      the implementation year of the admission policy for new smear positive pulmonary
      tuberculosis patients.
AB  - OBJECTIVE: To demonstrate the tuberculosis (TB) control activities in hospital
      and treatment success rate during the implementation year of the admission
      policy. MATERIAL AND METHOD: The hospital-based survey was conducted in 12
      provinces, five hospitals of each province. The medical records of hospitalized
      patients, with new sputum smear positive (NSS+) pulmonary tuberculosis (PTB),
      registered between October 2008 and September 2009 were reviewed, as well as the
      TB control activities. RESULTS: Fifty-one hospitals with complete hospital
      information were included Of 2,290 patients, less than half(46.1%) were
      hospitalized, while the treatment success rate was 83.8% (1,921 patients). This
      is slightly lower than World Health Organization target of 85%. In 2009, the six
      main control activities implemented in the studied hospital as part of the
      National Tuberculosis Program guideline of 15 items were 1) annual plan project
      for TB control program (51/51 hospitals, 100%), 2) protective equipment to
      prevent TB infection for personnel (50/51 hospitals, 98.0%), 3) appointment of
      committee in hospital for TB control program (49/51, 96.0%), 4) surveillance TB
      infection system in hospital for personnel (49/51, 96.0%), 5) protective
      equipment protection TB infection (mask) for patients and relatives (48/51
      hospitals, 94.1%), and 6) intensive health education for NSS+ PTB patients with
      admission (48/51 hospitals, 94.1%). CONCLUSION: During the implementation year of
      admission policy, the hospitalization rate was low and treatment success rate was
      not as high as expected. However the enhanced effect of program activities on
      admission and treatment success was not fully supported by the present study.

PMID- 24319847
TI  - Anal fissures in infants may be a pathognomonic sign of infants with cow's milk
      allergy.
AB  - OBJECTIVE: To study the association between analfissures and cow's milk allergy
      (CMA) in infants. METHODS AND METHOD: In a prospective study, 72 confirmed cases
      of CMA in infants were examined for anal fissure by pediatricians with five
      years' experience. A positive finding was defined as when an anal fissure was
      detected by at least two out of three examiners. RESULTS: Of infants with CMA
      with and without gastrointestinal GI symptoms, 79% and 83% had anal fissures,
      respectively The prevalence of anal fissure in these infants is significantly
      higher than in normal infants. CONCLUSION: Anal fissure may be a pathognomonic
      sign of cow's milk allergy in infants.

PMID- 24319848
TI  - Reliability and validity of thai version ROME III questionnaire for children with
      functional gastrointestinal disorders.
AB  - BACKGROUND: The ROME III diagnostic questionnaireforpediatric functional
      gastrointestinal disorders (FGIDs) is widely accepted as an essential tool for
      the diagnosis ofFGIDs in children and as a research tool. However, the
      questionnaire has not been translated into Thai. OBJECTIVE: To transpose the ROME
      III diagnostic questionnaire and to determine its validity and reliability in the
      Thai cultural setting. MATERIAL AND METHOD: The original English ROME III
      diagnostic questionnaire, composed of 71 items, was translated into Thai
      following permission from the ROME foundation. The ROME III questionnaire, Thai
      version was then translated back to English by a bi-lingual expert. The original
      English and the back-translation versions were compared and the validity was
      analyzed using Index ofl Item-Objective Congruence (IOC). Finally, the Thai
      questionnaire was tested with 50 healthy school-children aged four to 15 years
      old who had no serious illness. The questionnaire was answered by parents for
      children aged four to 10 years, and self-answered by children aged over 10 years.
      The reliability was evaluated by Cronbach's alpha coefficient. RESULTS: Item to
      item comparison between the original English and the back-translation versions
      valued by IOC was 0.94, which indicated high validity. The Cronbach's alpha
      coefficient of the overall 71 items was 0.98, which indicated high reliability.
      Moreover the alpha of reliability for self-report and parent-report was 0.96 and
      0.97 respectively. CONCLUSION: The ROME III diagnostic questionnaire in Thai is
      valid and reliable for the diagnosis of FGIDs in Thai children.

PMID- 24319849
TI  - Performance of motor imitation in children with and without dyspraxia.
AB  - BACKGROUND: Motor imitation is truly essential for young children to learn new
      motor skills, social behavior and skilled acts or praxis. The present study aimed
      to investigate motor imitation ability between typically-developing children and
      dyspraxic children and to examine the development trends in both children groups.
      MATERIAL AND METHOD: The comparison ofmotor imitation was studied in 55 typically
      developing children and 59 dyspraxic children aged 5 to 8 years. The Motor
      Imitation subtest consisted of two sections, imitation of postures and imitation
      of verbal instructions. Typically-developing children and dyspraxic children were
      examined for developmental trends. The independent samples t-test was used to
      analyze the differences between both groups. Two-way analysis of variance (ANOVA)
      was used to analyze inter-age differences for each age group. RESULTS: The
      results revealed significant differences between dyspraxic and typically
      developing children. Both typically-developing and dyspraxic children
      demonstrated age trends. The older children scored higher than younger children.
      CONCLUSION: Imitation is a primary learning strategy of young children. It is
      essential that children with dyspraxia receive early detection and need effective
      intervention. Typically-developing children and dyspraxic children showed higher
      mean score on the Imitation of Posture section than the Verbal Instructions
      section. Motor imitation competency, therefore, changes and improves with age.

PMID- 24319850
TI  - Retrospective long term outcome following microvascular decompression surgery in
      Thai patients with trigeminal neuralgia.
AB  - OBJECTIVE: To retrospectively evaluate 5-year pain-free symptoms and clinical
      outcome for trigeminal neuralgia (TN) patient population after microvascular
      decompression. MATERIAL AND METHOD: The authors reviewed the medical records of
      all Thai TN cases admitted at Ramathibodi Hospital, Mahidol University, and
      Ramkhamhaeng Hospital between 2001 and 2006. The 5-year pain-free symptoms and
      clinical outcome was determined using marginal homogeneity test (Stuart-Maxwell).
      RESULTS: There were 99 cases with TN. Women (75.6%) were affected more than men
      (24.4%). More often, the facial pain occurred on the right side of the face
      (72.8%) than on the left (27.2%). In 78.8% of cases, the facial pain was located
      along the mandibular division of the trigeminal nerve. In 19.2% of cases, the
      facial pain was located along the maxilla division ofthe trigeminal nerve and 30%
      of cases reported the pain along the combination ofthe maxilla and the mandibular
      division of the trigeminal nerve. Two percent of cases located pain along all
      three divisions. In 65.7% of cases, they reported their triggerpoints. Sixty-one
      cases (61.6%) were operated at Ramkhamhaeng Hospital and 38 cases (38.4%)
      [corrected] were diagnosed and treated at Ramathibodi Hospital, Mahidol
      University. Microvascular decompression surgery was the treatment of choice in
      all cases. As a final point, 97.9% of all cases who were pain free at the 5-year
      follow-up were significantly different between before and after treatment (p<
      0.001). CONCLUSION: In Thai TN patients, the mandibular division of the
      trigeminal nerve was most commonly involved, in concordance with other population
      group studies. In the present study, microvascular decompression surgery is the
      treatment of choice in TN patient. In the 97.9% of all cases that were pain free
      at the 5-year follow-up, they were significantly different between before and
      after treatment (p< 0. 001).

PMID- 24319851
TI  - Risk-associated mortality in patients with peritonitis due to Sandorica Koetjape
      seed ingestion: a retrospective study.
AB  - OBJECTIVE: To identify the factor associated with the mortality ofpatients with
      peritonitis due to Sandoricum koetjape seed ingestion. MATERIAL AND METHOD:
      Thirty patients who presented with peritonitis and had a history of Sandorica
      seed ingestion between September 2009 and August 2012 were retrospectively
      reviewed. Gender, age, comorbid, number of ingested seed, duration of symptom,
      body temperature, shock at initial admission, extent ofperitonitis, presence
      offree air under the dome of the diaphragm, white blood cell count, serum
      bicarbonate levels, resuscitation time, severity of intraabdominal contamination,
      perforated wound size, and operation methods were analyzed for their association
      with the mortality using Fisher s exact test. Odds ratio (OR) and 95% confidence
      interval (CI) were calculated to determine the strength of association. RESULTS:
      All patients received a definite diagnosis of Sandorica seed-induced colon
      perforation intraoperatively. Six of 30 patients died during 28-day
      hospitalization. The result showed that shock at initial admission (OR 35.0, 95%
      CI 2.9-411.4, p= 0.002), serum bicarbonate levels less than 15 mmol/L (OR 19.0,
      95% CI 1.7-201.6, p = 0.009), and severe intraabdominal contamination (OR 10.0,
      95% CI 1.3-74.5, p = 0.029) were the significant factors associated with the
      mortality. CONCLUSION: The factor-associated mortality in patients with
      peritonitis due to Sandorica seed ingestion was consistent with a clinical
      picture of septic shock. Early recognition and treatment of hypotensive episode
      accompanying with surgical correction and control of infection is therefore a key
      to improve the mortality outcome of this group of patients.

PMID- 24319852
TI  - The result of surgical treatment in patients with cerebral aneurysms in Maharaj
      Nakorn Chiang Mai Hospital: a report of 225 cases.
AB  - OBJECTIVE: Evaluate the result of intracranial aneurysm surgery in Maharaj Nakorn
      Chiang Mai Hospital. MATERIAL AND METHOD: A retrospective study ofpatients who
      underwent surgery for intracranial aneurysms between 2003 and 2007. The
      patients'age, gender, signs and symptoms, CT brain findings, Subarachnoid
      hemorrhage (SAH), World Federation of Neurosurgical Society grading (WFNS), and
      aneurysm location were studied and correlated with outcome after surgery.
      RESULTS: Two hundred twenty five patients ofintracranial aneurysm were operated
      on between 2003 and 2007. Two hundred nine patients (92%) had anterior
      circulation aneurysms and 18 (8%) had posterior circulation aneurysms. The
      outcome, as evaluated by Glasgow Outcome Scale (GOS), showed good recovery and
      moderate disability patients (142, 62.9%) were classified as favorable outcome
      group whereas patients with severe disability, vegetative state, and dead (83,
      36.9%) were classified as unfavorable outcome. According to WFNS grading, the
      patients with unruptured aneurysm and WFNS grade 1-2 had favorable outcome in 116
      patients (78.37%) and unfavorable outcome in 32 patients (21.62%). Whereas the
      patients with WFNS grade 3-5 had favorable outcome in 32 patients (33.76%) and
      unfavorable outcome in 51 patients (66.23%). CONCLUSION: This study of 225 cases
      revealed 142 cases with favorable outcome and 83 cases with unfavorable outcome.
      Factors that affected the outcome were WFNS grading and age.

PMID- 24319853
TI  - Video-assisted thoracic surgery lobectomy for lung cancer in Ramathibodi
      Hospital.
AB  - BACKGROUND: Although the public perceives video-assisted thoracic surgery (VATS)
      as advantageous because it is less invasive than a standard thoracotomy There are
      questioned the safety of VATS lobectomy and its adequacy as a cancer operation.
      This study is reviewed to assess this issue. MATERIAL AND METHOD: This
      retrospective study was performed between January 2009 and June 2011 in 58
      patients who underwent VATS for a standard anatomic lobectomy with lymph node
      sampled or dissection for lung cancer 43 women (74%) and 15 men (26%) and mean
      age 60.28+/-11.14 years. None of this study group had any pleural effusion or
      pleural dissemination. RESULTS: The most symptom and sign of patients with lung
      cancer were normal [48 cases (83%), 54 cases (93%) respectively]. The most risk
      factor was smoking [12 cases (20%)]. The most lobectomy of VATS lobectomy was
      right upper lobectomy [17 cases (29%)] and the longest duration of VATS lobectomy
      was left upper lobectomy was 237.00+/-38.60 minutes. Thirty-one patients (53.4%)
      were adenocarcinoma. The VATS lobectomy was adequate for lung cancer surgery
      because malignant cells were not found from cytologic study of pleural lavages.
      The conversion rate from VATS to standard thoracotomy lobectomy was seven cases
      (12%), which the common causes were pleural symphysis and inadequate one lung
      ventilation. The postoperative courses showed minimal blood transfusion (0.11+/
      0. 37u), intensive care unit (ICU) stay (0.61+/-0.56 days) and intercostal
      drainage (ICD) duration (6.10+/-5.79 days). There were no intra-and post
      operative death. Seven cases (12%) had many complications; the most complication
      was bacteria pneumonia. A case needed re-thoracotomy due to medical treatment
      failure for chylothorax. CONCLUSION: VATS lobectomy (anatomic lobectomy and lymph
      nodes sampled or dissection)for lung cancer can be performed with low morbidity
      and no mortality.

PMID- 24319854
TI  - Pain management after cardiac surgery: are we underestimating post sternotomy
      pain?
AB  - OBJECTIVE: Good pain management can improve the outcome of patient care after
      cardiac surgery. The intensity of pain after cardiac surgery is often underrated.
      Inadequate pain control can result in increased morbidity and length of hospital
      stay as well as lead to chronic pain. Therefore, the authors conducted a study to
      identify the prevalence and risk factors of moderate to severe pain after cardiac
      surgery including treatment and complication. MATERIAL AND METHOD: The present
      study was prospectively performed in the patients undergoing cardiac surgery with
      median sternotomy in Siriraj Hospital, a tertiary care center between July 2009
      and November 2010. Pain was assessed by numerical rating scale (NRS, 0-10) whilst
      NRS >4 was defined as moderate to severe pain. Pain score was recorded until 48
      hours after surgery. Demographic data, history ofprevious cardiac and non-cardiac
      surgery, chronic pain history, details of the operation, and intra-and
      postoperative analgesia were recorded, including complication ofpain treatment.
      In addition, pain expectation and experience were compared and the patient
      satisfaction was evaluated RESULTS: Two hundred ninety patients were enrolled,
      95.5% ASA physical status III, with mean duration of surgery 243.8 minutes (95
      600) and cardiopulmonary bypass time 112.8 minutes (33-500). The prevalence of
      moderate to severe pain in the patients after cardiac surgery was 61.4%. The
      duration of cardiopulmonary bypass less than 60 minutes decreased numbers of
      patients with moderate to severe pain with adjusted OR ratio of 0.40, 95% CI =
      0.16,1.004, (p<0.001). Complications of pain treatment were respiratory
      depression (0.7%), nausea (25.6%), vomiting (11.4%), pruritus (4.1%), and urinary
      retention (0.3%). The majority of the patients were satisfied with pain control
      (81.4%). CONCLUSION: The prevalence of moderate to severe pain in the present
      study was high and duration of cardiopulmonary bypass was the only factor
      affected Still, most patients were satisfied with the pain treatment.

PMID- 24319855
TI  - Sonographic findings of hepatocellular carcinoma detected in ultrasound
      surveillance of cirrhotic patients.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is associated with high mortality.
      Patients with hepatitis B or C viral cirrhosis have an increased risk of
      developing HCC. Ultrasound is the most widely used screening method, and is
      recommended by many guidelines. OBJECTIVE: To study the sonographic findings
      ofHCC detected in ultrasound surveillance of cirrhotic patients. MATERIAL AND
      METHOD: Retrospective assessment of ultrasoundfindings of all nodules that were
      diagnosed HCC by either dynamic imaging (CTor MRI) or biopsy between October 2008
      and July 2011. Nodules were classified based on echogenicity and other
      sonographic characteristics. RESULTS: Of 92 nodules, 42 (45.7%) were hyperechoic,
      29 (31.5%) hypoechoic, 20 (21.7%) heterogeneous echoic and 1 (1.1%) isoechoic.
      Heteroechoic nodules were more common among nodules over 3.0 cm (p = 0.0037)
      while hypoechoic nodules tended to be the smaller ones. About half (48/92) of the
      nodules had a hypoechoic halo and occurred significantly more commonly among
      hyperechoic and heteroechoic nodules (p< 0. 001). Posterior enhancement was found
      in 54 nodules (58. 7%0), also more common in nodules >3.0 cm (p = 018). Lateral
      shadowing occurred in 40 nodules (43.5%). CONCLUSION: The sonographic findings of
      HCC nodules in the present studies varied, but the prevalence of hyperechoic
      nodules was higher than in most of other studies. The authors emphasize the
      necessity of performing dynamic imaging for any nodule detected in a cirrhotic
      liver in order to exclude their neoplastic nature, no matter what it may look
      like.

PMID- 24319856
TI  - The influence of MR imaging on changes in patient counseling in obstetric
      patients with suspected fetal anomalies by ultrasound.
AB  - OBJECTIVE: To determine the frequency of additional information provided by
      magnetic resonance (MR) imaging in supplement to ultrasound (US) in patients with
      fetal anomaly and to determine the influence of MR imaging findings on patient
      counseling. MATERIAL AND METHOD: MR imaging offetus was performed in 26 patients
      who have abnormal ultrasound results. Referring obstetricians were asked about
      how the additional information provided by MR imaging have effect on their
      decision marking, patient counseling, and case management. RESULTS: MR imaging in
      23 of 26 fetuses was technically successful. MR imaging provided additional
      information in 14/23 (60.9%) cases. In the other nine (39.1%) cases, MR imaging
      confirmed US diagnosis but did not give supplementary information. Additional
      information from MR imaging affected patient counseling in five (21.7%) cases and
      did not affect patient counseling in the other nine (39.1%) cases. In 14 cases
      with additional information from MR imaging, there were isolated CNS involvement
      in five (35.7%) cases, isolated extra-CNS involvement in two (14.3%) cases,
      multisystem involvement in five (35.7%) cases, and other-category in two (14.3%)
      case. CONCLUSION: MR imaging can provide additional information that have
      influence on patient counseling and patient care, particularly in cases with CNS
      and multisystem anomaly.

PMID- 24319857
TI  - The sensitivity and specificity of a urine leukocyte esterase dipstick test for
      the diagnosis of urinary tract infection in the outpatient clinic of Rajavithi
      Hospital.
AB  - BACKGROUND: Urinary tract infection (UTI) is frequentlyfound in family physician
      clinics. The present study was designed to assess the reliability of a leukocyte
      esterase urine dipstick test in detecting UTI. OBJECTIVE: Compare the performance
      and reliability ofleukocyte esterase dipstick urinalysis with microscopic
      examination for detection of clinically suspected UTI. MATERIAL AND METHOD: A
      retrospective descriptive study was conducted on 109 patients who visited the
      outpatient clinic with a clinical suspicion of UTI between November 2010 and July
      2011. The subjects consisted ofpatients from the age of 15 years and over
      regardless of gender A dipstick test (Combur-Test Mstrip, Roche) was used. All
      dipstick-positive samples were processed to microscopic examination and urine
      culture was used as gold standard. Sensitivity, specificity, and predictive
      values were analyzed for the dipstick test (leukocyte esterase) as compared to
      microscopic examination. Statistical analysis was performed by using the t-test.
      RESULTS: The sensitivity of leukocyte esterase test and the combined leukocyte
      esterase and nitrite test were 63.6% and 66.7%, respectively. The presence of
      pyuria demonstrated the highest sensitivity (95.6%) and specificity (60.9%) for
      positive urine culture compared to the dipstick test. Statistical analysis
      revealed a significant correlation between the dipstick test (leukocyte esterase)
      and microscopic examination (p< 0. 001). CONCLUSION: Pyuria can be used to detect
      UTI instead of urine culture due to its significant incidence. In the present
      study, the presence of pyuria had a higher specificity (60.9%) compared to the
      dipstick test (44.2%). However the significantly positive dipstick and pyuria
      results make the combined test more useful than the single test, and there is a
      statistically significant correlation between the dipstick test (leukocyte
      esterase) and the microscopic examination (p< 0. 001). Therefore, the dipstick
      test (leukocyte esterase) can be used as a diagnostic tool in detecting UTI
      cases.

PMID- 24319858
TI  - Follow-up the outcome of treatment of inhalant users in Northeastern Thailand.
AB  - BACKGROUND: Drug treatment in Thailand is categorized into three types, namely
      voluntary system, correctional system, and compulsory system. The latter is under
      Inhalants Law and Drug Addict Rehabilitation Act 2002 A.D. OBJECTIVE: Follow-up
      the outcome of the compulsory system treatment in inhalant user on probation
      program and evaluate hospital referrals and the process of follow-up in
      community. MATERIAL AND METHOD: A survey questionnaire adopted from KKU-VOUDIT
      was used in the present study in nine selected provinces of Thailand. Nine
      hundred ninety two people formed the study population and were divided into 95
      administrators, 71 stakeholders, and 760 inhalant users. RESULTS: Inhalant users
      were classified as experimental (56.8%), harmful (24.2%), dependent (13.9%), and
      psychosis (5.1%). Majority of inhalant users were male (95.0%), 12 to 19 (61.3%),
      single (83.4%). In this group, 15.5% were students while 45.1% were temporarily
      employed, and 40.3% were unemployed. Most inhalant users never reused (72.2%).
      However some users re-used but were not incarcerated (12.2%) while others re-used
      and were incarcerated (15.5%). CONCLUSION: As the targets are youths, sub
      district administrative organization, basic education office, and primary
      healthcare organizations should come together to bring about necessary changes.

PMID- 24319859
TI  - Using MoCA-Thai to evaluate cognitive impairment in patients with schizophrenia.
AB  - BACKGROUND: Schizophrenia is a chronic devastating illness with specific effects
      on cognitive function. A few studies have been performed on Asian patients.
      OBJECTIVE: To examine prevalence of cognitive impairment and associated factors
      in Thai patients with schizophrenia. MATERIAL AND METHOD: A descriptive cross
      sectional study of patients with schizophrenia that were selected consecutively
      from a psychiatric outpatient clinic at Srinagarind Hospital, Khon Kaen
      University between June 2008 andDecember 2009 was conducted. The Montreal
      Cognitive Assessment-Thai version (MoCA-T) test was used to evaluate cognitive
      functions. Associated factors such as age of onset, type of antipsychotics were
      assessed by collecting data from medical records. Data analysis used descriptive
      statistics, and univariate analysis used Chi-square. RESULTS: Seventy-five
      patients with schizophrenia were recruited The majority of cases was single,
      male, had low education, and manifested paranoia. The prevalence of cognitive
      impairment was 81.3%. Significant factors associated with cognitive impairment
      were the year of education lower than 12 (OR = 9.25, 95% CI 1.90-45.03, p =
      0.002) and those who had taken typical and combined antipsychotic drugs (OR =
      5.97, 95% CI 1.66-21.55, p = 0.005). CONCLUSION: Thai patients with schizophrenia
      showed a high prevalence of cognitive impairment. Therefore, clinicians should
      assess cognitive function and cognitive remedy

PMID- 24319860
TI  - Massive hemothorax due to intrathoracic extramedullary hematopoiesis in a patient
      with beta thalassemia hemoglobin E disease.
AB  - Case report of a 28-year-old man with beta thalassemia/hemoglobin E disease who
      developed a massive hemothorax due to bleeding from multiple large intrathoracic,
      paraspinal hematopoietic masses. Initially, a thoracotomy was required for the
      control of bleeding. Postoperatively, the patient received 2,000 ml of packed red
      cells but he continued bleeding after the blood chemistries and coagulopathy
      specimen were corrected. The decision was made to return to the operating room
      for a thoracotomy to control the bleeding. However, before re-operating, the
      patient underwent a collapse and failed resuscitation. This complication has
      never been previously reported in Thailand.

PMID- 24319861
TI  - Hypoimmunoglobulinemia and protein C deficiency in a girl with Jacobsen syndrome:
      a case report.
AB  - Jacobsen syndrome is a rare contiguous gene syndrome caused by partial deletion
      of the long arm of chromosome 11. The typical clinical manifestations include
      physical growth retardation, mental retardation,facial dysmorphisms, congenital
      heart disease, thrombocytopenia, or pancytopenia. A Thai-Australian girl was born
      with multiple abnormalities. Typical features and her karyotype, 46, XX, del(ll)
      (q23-qter), confirmed Jacobson syndrome. She had many uncommon findings including
      upslanting palpebral fissures, tortuousity of retinal vessels and
      hypogammaglobulinemia. In addition, this case also presented with protein C
      deficiency, which has not been reported previously in Jacobsen syndrome. The
      patient was treated with phototherapy, intravenous antibiotic injection, and
      platelet transfusion in neonatal period. Cranioplasty was performed for
      prevention of the increased intracranial pressure at three months of age.
      Surgical correction for strabismus was in the treatment plan.

PMID- 24319862
TI  - Epstein-Barr Virus associated primary intracranial smooth muscle tumor in HIV
      positive patient: case report and review of the literature.
AB  - The authors report a case of HIV-positive patient with primary intracranial
      smooth muscle tumor Evidence of Epstein-Barr Virus (EB V) infection in this tumor
      is proven by in situ hybridization for EBV-encoded RNA (EBER). Review of the
      literature shows that the occurring of smooth muscle tumor at intracranial site
      is extremely rare and most cases are HIV-infected patient. It also shows an
      association with EBV infection.

PMID- 24319863
TI  - Helping you meet the new--and some of the old--demands of healthcare delivery in
      2014.

PMID- 24319864
TI  - Processes for documenting self-pay patients.

PMID- 24319865
TI  - MGMA comments on proposed 2014 Medicare physician fee schedule.

PMID- 24319866
TI  - Coding differences between ICD-9 and ICD-10. A look at the musculoskeletal
      system.

PMID- 24319867
TI  - Brainstorming is dead: 3 more-effective approaches to generating ideas.

PMID- 24319868
TI  - Bigger is usually better: in the right circumstances, large groups outperform
      their smaller peers.

PMID- 24319869
TI  - Digging for gold. Data mining yields better health outcomes and profits for
      practice professionals who seek improvements to care delivery.

PMID- 24319870
TI  - Jumping into the deep end of the data pool.

PMID- 24319871
TI  - Patient portals improve satisfaction and streamline processes.

PMID- 24319872
TI  - Leaders among you: MGMA award-winners drive improvement.

PMID- 24319873
TI  - Patient satisfaction survey leads to operational changes.

PMID- 24319874
TI  - Is it flirtation or real love?

PMID- 24319875
TI  - A clear new lens.

PMID- 24319876
TI  - The workplace condition. Dos and don'ts for increasing morale.

PMID- 24319877
TI  - Heroes. Are we a little too loosey-goosey with that word?

PMID- 24319878
TI  - An ounce of prevention. Recommendations for improving employee hiring practices.

PMID- 24319879
TI  - 'About to die'. Motor vehicle crash patient presents puzzling trauma injury.

PMID- 24319880
TI  - Within reach. The possibilities are endless when imagining the ambulance of the
      future.

PMID- 24319881
TI  - Potentially fatal mistakes. Why pediatric dosing errors happen & how to avoid
      them.
AB  - Calls involving critically ill or injured children are some of the most stressful
      situations EMS providers encounter. Their anxiety can be exponentially compounded
      with the sudden realization that precise mathematical equations must be rapidly
      performed "in the moment," making a challenging situation even worse at a time
      when there is no room for error. To help avoid these potentially devastating
      mistakes, all providers need to be aware of their vulnerability to pediatric
      dosing errors, and organizations need to support personnel with the training and
      resources necessary to mitigate these risks as much as possible.

PMID- 24319882
TI  - First-hand approach. A novel method to rapidly calculate pediatric drug dosages.
AB  - ROSC should ideally be achieved prior to departure from the scene. Airway
      maintenance and post-resuscitation care become top priorities en route to the
      closest appropriate facility. The entire sequence should appear effortless and
      smooth, creating the perception of impeccable excellence. Giving providers a
      method of calculation prior to arrival on the scene of a pediatric resuscitation
      helps them focus on the essential aspects of the call. With improved confidence,
      these essentials are accomplished rapidly on scene without hesitation or
      trepidation, and, most importantly, without the need for calculation of drug
      dosages.

PMID- 24319883
TI  - Respect your elders. Special considerations for EMS response to geriatric
      patients.
AB  - A variety of chronic pathologies often come along with the aging process and are
      experienced by many patients in late adulthood. EMS providers must be aware of
      the various challenges of transporting the geriatric population. And although an
      emphasis is often placed on the physical and medical issues associated with this
      population, it's also imperative to look at the whole picture to help prevent
      issues before they become an emegent problem. This includes being vigilant for
      elder abuse and neglect, as well as potential home hazards-including fall
      potentials and maintaining colder home temperatures-and dangerous cost-cutting
      measures, such as sharing medications. Prevention is key to helping older
      patients avoid potentially devastating situations, such as falls, medication
      errors and urban hyperthermia. But when those situations happen and providers are
      called to care for an older patient, compassion and demeanor are necessary to
      make this more vulnerable patient population comfortable and safe.

PMID- 24319884
TI  - Keeping it open. Emphasizing physical restraint when teaching advanced airway
      management.
AB  - An unrecognized advanced airway displacement is one of the most devastating
      events a critically ill or injured patient can suffer. Teaching our students to
      properly restrain the airway and limit neck and body movement every time they
      practice the skill is essential. Combining these skills with proper monitoring
      and documentation ensures the best possible outcome for our patients, and protect
      themselves from a potentially devastating clinical error. As educators, we can
      improve this important part of airway management.

PMID- 24319885
TI  - Flexed & perplexed. A guide to EMS assessment of injuries to the hand & wrist.

PMID- 24319886
TI  - Strugging to breathe. Decision making in the assessment & treatment of acute
      respiratory distress.
AB  - Acute respiratory distress is a common and often serious emergency. Good patient
      outcomes require rapid and skilled assessment of the airway, breathing and
      oxygenation. The ability to assess work of breathing and knowing when and how to
      intervene before a patient with acute respiratory distress tires will enhance
      your ability to care for this challenging complaint.

PMID- 24319887
TI  - Deep trauma. The detection, assessment & treatment of chest wounds.

PMID- 24319888
TI  - Ties that bind us. Putting up with a patient's family members.

PMID- 24319889
TI  - [Raising problem awareness of the "nutrition" topic].

PMID- 24319890
TI  - ["Nursing does not have the status it deserves". Pro].

PMID- 24319891
TI  - ["Nursing chambers are a costly placebo". Contra].

PMID- 24319892
TI  - [The biggest concern is a possible need for nursing care].

PMID- 24319893
TI  - [Better health for body and soul].

PMID- 24319894
TI  - [A core responsibility of nursing].

PMID- 24319895
TI  - [Hand in hand].

PMID- 24319896
TI  - [Promoting oral feeding].

PMID- 24319897
TI  - ["I have no appetite"].

PMID- 24319898
TI  - [For the purpose and benefit of the patient].

PMID- 24319899
TI  - [Exposure to aggressive patient behaviour and its' association with the nurses'
      "work ability" in Germany].
AB  - BACKGROUND: Aggressive behavior and violence in patients, residents or clients
      are growing challenges in nursing. Aggressive behavior can have both, physical
      and psychological consequences for nurses and can lead to a reduced performance
      at work, demotivation, sickness absence and the premature exit from the nursing
      profession. To develop purposive strategies and to deal with aggressive behavior
      and health promotion programs, it is crucial to know more about the prevalence of
      aggressive behavior from patients and the effect on the work ability of nurses in
      different types of institutions. METHOD: Data of 1735 German nurses was derived
      from the European NEXT-Study. Description and analysis of variance for each
      working area (hospital ward, Intensive Care Unit, psychiatric ward, nursing home
      and home care) were conducted. The work ability was measured with the Work
      Ability Index (WAI). The aggressive behavior was measured by one item developed
      by the NEXT Study Group. Linear regression models were applied to analyze the
      effect of aggressive behavior on the work ability of nurses in a comparison of
      the five different working areas. RESULTS: A total of 84.9 percent of the nurses
      were "sometimes" or "often/always" confronted with aggressive behavior from
      patients. In the comparison of the five working areas, nurses were exposed to
      different levels of aggressive behavior, while differences in the work ability of
      nurses were also observed. It was found that aggressive behavior from patients
      was associated with reduced work ability in nurses working in hospital wards,
      nursing homes and home care, but not nurses working in ICUs and psychiatric
      wards. CONCLUSIONS: The findings indicate that many nurses in Germany are exposed
      to aggressive behavior from patients, which has negative effect on the nurses'
      work ability. However, it is assumed that strategies to deal with aggressive
      behavior could play a buffer role between aggressive behavior and work ability of
      nurses, highlighting one possibility of intervention in future.

PMID- 24319900
TI  - [Dialysis patients: screening by nursing staff shall prevent malnutrition].

PMID- 24319901
TI  - [Obesity and overweight in elderly disabled patients].

PMID- 24319902
TI  - [Reducing and rationing].

PMID- 24319903
TI  - [Improved regulation for chronic patients].

PMID- 24319904
TI  - [Up to 70 hours of duty per week].

PMID- 24319905
TI  - [Why we get cancer - and why not].

PMID- 24319906
TI  - [What does not help also harms nothing?!].

PMID- 24319907
TI  - Getting off to a good start.

PMID- 24319908
TI  - The evolution of mental health care.
AB  - By eliminating the historic separation between behavioral and physical health
      care, providers are delivering better care faster and at less expense.

PMID- 24319910
TI  - A trustee's guide to common ACA questions.

PMID- 24319909
TI  - Parallel paths to realignment.
AB  - Consolidation patterns in the commercial banking industry offer lessons for
      health care leaders.

PMID- 24319911
TI  - In search of a perfect partner.
AB  - When a financially stable sole community provider sought to affiliate with
      another hospital, its leaders encountered unexpected complications.

PMID- 24319912
TI  - Inspiring a greener future.
AB  - Thee board can lead the change to a culture of sustainability.

PMID- 24319913
TI  - Ready for the unthinkable.

PMID- 24319914
TI  - Mission-driven population health.

PMID- 24319915
TI  - Quality measures in pediatric hospital medicine: Moneyball or looking for Fabio?

PMID- 24319916
TI  - Parental attitudes toward obesity and overweight screening and communication for
      hospitalized children.
AB  - OBJECTIVE: Many studies have evaluated BMI screening, communication, and follow
      up recommendations in the outpatient setting. However, few studies have examined
      parental attitudes toward using the inpatient setting as a time to screen and
      counsel families regarding their child's BMI. We sought to study parental
      attitudes about overweight and obesity screening in the inpatient setting.
      METHODS: Parents (N= 101) of children aged 2 to 18 years admitted to a general
      pediatric hospital or surgical service were queried regarding their attitudes
      about screening and counseling for overweight and obesity. Children's age,
      gender, height, weight, and diagnosis codes were extracted from electronic
      medical records and billing databases. BMI was calculated, plotted, and
      categorized according to standard Centers for Disease Control and Prevention
      growth charts and expert recommendation. RESULTS: Fourteen percent of children in
      the study were overweight, and 17% were obese. Parents of overweight and obese
      children underestimated their child's weight status 68% of the time. The majority
      believed admitted children should always have their BMI calculated. Almost all
      parents (90%) indicated that their inpatient physician should inform them if
      their child were overweight or obese and that primary care providers should be
      informed of the results of BMI screening. CONCLUSIONS: Parents of children
      admitted to the hospital believed their children should have their BMI screened.
      If their child was overweight or obese, parents believed they should be informed,
      and counseling should be initiated. These findings support using the inpatient
      time to screen and communicate BMI.

PMID- 24319917
TI  - Prevalence, characteristics, and opinions of pediatric rapid response teams in
      the United States.
AB  - OBJECTIVE: Rapid response teams (RRTs) have been proposed as patient safety
      initiatives for hospitalized children. The aim of this study was to determine the
      prevalence, characteristics, and opinions of RRTs in hospitals with PICUs in the
      United States. METHODS: This study was conducted as a cross-sectional survey of
      PICU physicians in adult and children's hospitals that care for children. One
      survey was sent to the PICU medical director in each hospital. The primary
      outcome was the presence of an RRT. Other outcomes included RRT characteristics
      and beliefs regarding their impact on patient safety. RESULTS: The survey
      response rate was 64% (134 of 210). Of the responding institutions, 79% (103) had
      an RRT; most of these teams were implemented in the last 5 years. Family
      activation was present in 69%, and automatic triggers existed in 34% of cases.
      RRTs included a median of 3 members and were composed of physicians in 77%,
      nurses in 100%, and respiratory therapists in 89% of institutions. Respondents
      with RRTs were more likely to agree that RRTs improve patient safety than
      respondents without RRTs (76% vs 52%) and more likely to disagree that they are
      not worth the money invested (82% vs 63%). CONCLUSIONS: Although the evidence and
      opinions on the benefit of RRTs are mixed, the majority of US hospitals with
      PICUs have implemented RRTs. These systems demonstrate variability in activation
      mechanisms and team composition. Hospitals may be empirically adopting these
      initiatives without knowledge of the specific characteristics that are optimal
      for patient outcomes.

PMID- 24319918
TI  - Career satisfaction and the role of mentorship: a survey of pediatric
      hospitalists.
AB  - BACKGROUND AND OBJECTIVE: Attending physicians' career satisfaction is associated
      with higher patient satisfaction, better patient care, and even medical student
      career choice. Previous studies indicate that adequate mentorship improves job
      satisfaction, but finding mentors may be challenging for some hospitalists.
      Little is known about pediatric hospitalist career satisfaction or the role of
      mentorship. The goal of this study was to assess career satisfaction among
      pediatric hospitalists, determine which interventions may improve satisfaction,
      and investigate the role of mentorship in satisfaction. METHODS: This study
      included the use of an anonymous electronic cross-sectional survey sent to the
      American Academy of Pediatrics' Section on Hospital Medicine Listserv between
      November 2009 and January 2010. RESULTS: A total of 222 pediatric hospitalists
      responded; 92% agreed with the statement, "Overall, I am pleased with my work."
      Of the 23 satisfaction statements, "I have adequate mentorship in my career" was
      rated lowest (< or = .001); only 44% agreed. Adequate mentorship was
      significantly correlated with overall career satisfaction, having sufficient
      opportunity for promotion, feeling valued by one's administration, and wishing to
      remain at one's current hospital. Adequate mentorship was negatively correlated
      with planning to change specialty or leave clinical medicine. Mentorship
      satisfaction did not differ by age, years as a hospitalist, gender, or practice
      setting. Of the 15 potential interventions, creating a formal mentorship program
      ranked in the top 5. Only increasing base salary received a significantly higher
      score. CONCLUSIONS: Although surveyed hospitalists have substantial overall
      career satisfaction, lack of mentorship is a significant problem that spans the
      demographic spectrum. Establishing a mentorship program may be an effective way
      for hospitalist groups to improve satisfaction.

PMID- 24319919
TI  - Pediatric hospitalist research productivity: predictors of success at presenting
      abstracts and publishing peer-reviewed manuscripts among pediatric hospitalists.
AB  - OBJECTIVE: To identify factors associated with research productivity among
      pediatric hospitalists. METHODS: We performed a cross-sectional online survey of
      pediatric hospitalists recruited from the American Academy of Pediatrics Section
      on Hospital Medicine from May to August 2009. We used abstract presentations at a
      national meeting (intermediate outcome) and 22 first-author peer-reviewed
      manuscripts (primary outcome) to measure research productivity. Information was
      also collected on environmental and physician characteristics. Stepwise logistic
      regression was performed to identify independent associations with research
      productivity. RESULTS: Two hundred fifteen pediatric hospitalists completed the
      survey. The respondents included 82% in an academic environment, 150% fellowship
      trained, 25% with additional degrees, and 67% with no protected time for
      research. Fifty-six percent presented an abstract, and 17% had 2 or more
      publications. After adjusting for potential confounders, pediatric hospitalists
      were more likely to have presented an abstract if they had fellowship training,
      an additional degree, were "very interested" or "interested" in performing
      research, or worked in a free-standing children's hospital or children's hospital
      within a hospital. Pediatric hospitalists were more likely to have 2 or more
      publications if they had an additional degree or had presented an abstract.
      CONCLUSIONS: Among pediatric hospitalists, obtaining an additional degree and
      presenting an abstract at a national meeting are associated with research
      productivity. A minority of this group of pediatric hospitalists had fellowship
      training, degree training, or 2 or more first-author manuscripts published even
      though the majority are in an academic environment. These results suggest that
      structured training and a focus on abstract presentations at meetings could be a
      programmatic solution.

PMID- 24319920
TI  - Pediatric renal abscess: a 10-year single-center retrospective analysis.
AB  - OBJECTIVE: The objective of this retrospective series is to describe the
      demographics and treatment of patients with renal abscesses and to determine if
      abscess size influences management. METHODS: We reviewed all pediatric cases of
      renal abscesses treated over a 10-year period in our medical center. Clinical,
      laboratory, imaging data, and treatment modalities were analyzed. RESULTS: Thirty
      six patients were evaluated, with renal abscesses found in all age groups. The
      median age was 9.3 years, and 64% of patients affected were female. Fever and
      abdominal pain were the most common clinical symptoms. A premorbid genitourinary
      condition was present in 310/a of patients. Previous urinary tract infection was
      documented in 31% of the cases. Initial elevation of C-reactive protein or
      erythrocyte sedimentation rate, when obtained, was observed in >80% of cases.
      Abnormal urinalysis was recognized in two-thirds of encounters. Escherichia coli,
      the most common microorganism isolated, was found in half the cases.
      Staphylococcus aureus was isolated in 11%. Ultrasound and computed tomography
      were the most used diagnostic imaging modalities. Eighty-nine percent of the
      patients who received intravenous antibiotics alone as an initial treatment
      regimen did not require percutaneous drainage or surgery. CONCLUSIONS: Ten of the
      14 patients with an abscess size > or =3 cm had an invasive intervention, but
      only 1 of these 10 had an initial 48-hour trial of antibiotics alone. In
      contrast, only 2 of the 22 patients who had an abscess size <3 cm received an
      invasive intervention (Fisher P= .0002). We conclude that conservative treatment
      with intravenous antibiotics may be a reasonable initial approach.

PMID- 24319921
TI  - When should DVT be suspected in children with osteomyelitis?
AB  - BACKGROUND: There is increasing recognition that deep venous thrombosis (DVT) is
      a complicating factor in some children with acute hematogenous osteomyelitis. The
      similarity in signs and symptoms of osteomyelitis and DVT make clinical
      recognition of this complicating condition difficult. It would be helpful to the
      clinician to identify by other means which children with osteomyelitis are at
      greatest risk for DVT. We reviewed the available literature regarding
      osteomyelitis and DVT in children to identify potential characteristics of
      children with osteomyelitis that puts them at risk for concurrent DVT. METHODS:
      We performed searches of the PubMed, Cochrane, CINAHL, and National Guideline
      Clearinghouse databases on the topic of osteomyelitis and thrombosis in children
      0 to 18 years of age from 2001 to the present. RESULTS: Four studies were
      included: 3 retrospective and 1 prospective. Studies varied in terms of clinical,
      laboratory, and imaging parameters evaluated. Overall they suggest trends toward
      increased incidence of DVT in children who were critically ill at presentation,
      had positive blood cultures, were infected with methicillin-resistant
      Staphylococcus aureus, had an elevated C-reactive protein, and had central venous
      catheters placed. CONCLUSIONS: Strong consideration should be given to evaluating
      children with osteomyelitis for DVT if they are critically ill at presentation,
      particularly if they have pulmonary findings, are persistently bacteremic,
      especially with methicillin-resistant S aureus.

PMID- 24319922
TI  - Enterovirus meningitis with marked pleocytosis.

PMID- 24319923
TI  - How should I manage a patient with presumed encephalitis and neuropsychiatric
      symptoms?

PMID- 24319924
TI  - An approach to teaching interdisciplinary health care to preclerkship medical
      students.

PMID- 24319925
TI  - My journey toward mindfulness: a personal narrative.

PMID- 24319926
TI  - Changing pitch of sounds alters perceived visual motion trajectory.
AB  - Several studies have examined the effects of auditory stimuli on visual
      perception. In studies of cross-modal correspondences, auditory pitch has been
      shown to modulate visual motion perception. In particular, low-reliability visual
      motion stimuli tend to be affected by metaphorically or physically congruent or
      incongruent sounds. In the present study, we examined the modulatory effects of
      auditory pitch on visual perception of motion trajectory for visual inputs of
      varying reliability. Our results indicated that an auditory pitch implying the
      illusory motion toward the outside of the visual field-modulated perceived motion
      trajectory. In contrast, auditory pitch implying the illusory motion toward the
      central visual field did not affect the perception of motion trajectory. This
      asymmetrical effect of auditory stimuli occurred depending on the reliability of
      the visual input. Moreover, sounds that corresponded in terms of their pitch
      elevation mapping altered the perception of the trajectory of visual motion when
      apparent motion could be perceived smoothly. Therefore, the present results
      demonstrate that auditory stimuli modulate visual motion perception especially
      when smooth motion is perceived in the peripheral visual field.

PMID- 24319927
TI  - A mechanism for detecting coincidence of auditory and visual spatial signals.
AB  - Information about the world is captured by our separate senses, and must be
      integrated to yield a unified representation. This raises the issue of which
      signals should be integrated and which should remain separate, as inappropriate
      integration will lead to misrepresentation and distortions. One strong cue
      suggesting that separate signals arise from a single source is coincidence, in
      space and in time. We measured increment thresholds for discriminating spatial
      intervals defined by pairs of simultaneously presented targets, one flash and one
      auditory sound, for various separations. We report a 'dipper function', in which
      thresholds follow a 'U-shaped' curve, with thresholds initially decreasing with
      spatial interval, and then increasing for larger separations. The presence of a
      dip in the audiovisual increment-discrimination function is evidence that the
      auditory and visual signals both input to a common mechanism encoding spatial
      separation, and a simple filter model with a sigmoidal transduction function
      simulated the results well. The function of an audiovisual spatial filter may be
      to detect coincidence, a fundamental cue guiding whether to integrate or
      segregate.

PMID- 24319928
TI  - Auditory-visual aversive stimuli modulate the conscious experience of fear.
AB  - In a natural environment, affective information is perceived via multiple senses,
      mostly audition and vision. However, the impact of multisensory information on
      affect remains relatively undiscovered. In this study, we investigated whether
      the auditory-visual presentation of aversive stimuli influences the experience of
      fear. We used the advantages of virtual reality to manipulate multisensory
      presentation and to display potentially fearful dog stimuli embedded in a natural
      context. We manipulated the affective reactions evoked by the dog stimuli by
      recruiting two groups of participants: dog-fearful and non-fearful participants.
      The sensitivity to dog fear was assessed psychometrically by a questionnaire and
      also at behavioral and subjective levels using a Behavioral Avoidance Test (BAT).
      Participants navigated in virtual environments, in which they encountered virtual
      dog stimuli presented through the auditory channel, the visual channel or both.
      They were asked to report their fear using Subjective Units of Distress. We
      compared the fear for unimodal (visual or auditory) and bimodal (auditory-visual)
      dog stimuli. Dog-fearful participants as well as non-fearful participants
      reported more fear in response to bimodal audiovisual compared to unimodal
      presentation of dog stimuli. These results suggest that fear is more intense when
      the affective information is processed via multiple sensory pathways, which might
      be due to a cross-modal potentiation. Our findings have implications for the
      field of virtual reality-based therapy of phobias. Therapies could be refined and
      improved by implicating and manipulating the multisensory presentation of the
      feared situations.

PMID- 24319929
TI  - The time-course of the cross-modal semantic modulation of visual picture
      processing by naturalistic sounds and spoken words.
AB  - The time-course of cross-modal semantic interactions between pictures and either
      naturalistic sounds or spoken words was compared. Participants performed a
      speeded picture categorization task while hearing a task-irrelevant auditory
      stimulus presented at various stimulus onset asynchronies (SOAs) with respect to
      the visual picture. Both naturalistic sounds and spoken words gave rise to cross
      modal semantic congruency effects (i.e., facilitation by semantically congruent
      sounds and inhibition by semantically incongruent sounds, as compared to a
      baseline noise condition) when the onset of the sound led that of the picture by
      240 ms or more. Both naturalistic sounds and spoken words also gave rise to
      inhibition irrespective of their semantic congruency when presented within 106 ms
      of the onset of the picture. The peak of this cross-modal inhibitory effect
      occurred earlier for spoken words than for naturalistic sounds. These results
      therefore demonstrate that the semantic priming of visual picture categorization
      by auditory stimuli only occurs when the onset of the sound precedes that of the
      visual stimulus. The different time-courses observed for naturalistic sounds and
      spoken words likely reflect the different processing pathways to access the
      relevant semantic representations.

PMID- 24319930
TI  - Vestibular perception is slow: a review.
AB  - Multisensory stimuli originating from the same event can be perceived
      asynchronously due to differential physical and neural delays. The transduction
      of and physiological responses to vestibular stimulation are extremely fast,
      suggesting that other stimuli need to be presented prior to vestibular
      stimulation in order to be perceived as simultaneous. There is, however, a recent
      and growing body of evidence which indicates that the perceived onset of
      vestibular stimulation is slow compared to the other senses, such that vestibular
      stimuli need to be presented prior to other sensory stimuli in order to be
      perceived synchronously. From a review of this literature it is speculated that
      this perceived latency of vestibular stimulation may reflect the fact that
      vestibular stimulation is most often associated with sensory events that occur
      following head movement, that the vestibular system rarely works alone, that
      additional computations are required for processing vestibular information, and
      that the brain prioritizes physiological response to vestibular stimulation over
      perceptual awareness of stimulation onset. Empirical investigation of these
      theoretical predictions is encouraged in order to fully understand this
      surprising result, its implications, and to advance the field.

PMID- 24319931
TI  - 2013 AHIMA Triumph Award winners.

PMID- 24319932
TI  - Keeping information clean. New information governance efforts challenge him to
      sort out dirty data.

PMID- 24319933
TI  - Medical records' dynamic nature. If it isn't written down, it didn't happen. And
      if it is written down, it might not be what it seems.

PMID- 24319934
TI  - Often mismatched shoes of healthcare.

PMID- 24319935
TI  - Five risky HIE practices that threaten data integrity.

PMID- 24319936
TI  - Step inside the physician's head. EHRs can enhance a physician's cognitive
      processing and eliminate diagnostic errors, with some HIM-led changes.

PMID- 24319937
TI  - Checking in on accounting of disclosures.

PMID- 24319938
TI  - Information governance's privacy and security component.

PMID- 24319939
TI  - Resolving problem list problems. HIM's role in maintaining an effective EHR
      problem list.

PMID- 24319940
TI  - Governance apples and oranges. Differences exist between information governance,
      data governance, and IT governance.

PMID- 24319941
TI  - Data standards, data quality, and interoperability (updated).

PMID- 24319943
TI  - Coding root operations with ICD-10-PCS. Understanding bypass, inspection, and
      map.

PMID- 24319942
TI  - New and revised ICD-10-CM obstetric guidelines.

PMID- 24319944
TI  - [Subcellular localization of severe fever with thrombocytopenia syndrome virus in
      macrophages].
AB  - OBJECTIVE: To study the subcellular localization of severe fever with
      thrombocytopenia syndrome virus (SFTSV) in macrophages and understand the
      replication and assembly mechanism of SFTSV in host cells. METHODS: Using two
      types of human macrophage cell lines THP-1 and U937, the study analyzed the
      intracellular colocalization of SFTSV with Golgi apparatus and endoplasmic
      reticulum by immunefluorescence staining and confocal microscopy. RESULTS: SFTSV
      infected macrophage cell lines THP-1 and U937. Immunofluorescence staining showed
      that the SFTSV nuclear protein colocalized with Golgi apparatus and closely
      surrounded by endoplasmic reticulum in the perinuclear region. CONCLUSION: The
      results suggested that Golgi complex and endoplasmic reticulum are probably the
      sites for formation and maturation of SFTSV viral particles.

PMID- 24319945
TI  - [The epidemiological characteristics of group C rotavirus in Lulong area and the
      analysis of diversity of VP6 gene].
AB  - OBJECTIVE: To study the epdimiology characteristics and the diversity of VP6 gene
      of GCRV in Lulong, and to provide the basis for GCRV in-depth research. METHODS:
      793 stool specimens from porcine with diarrhea or not from Lulong in 2007 and
      2008. GCRV was detected by nested multiple reverse transcription- polymerase
      chain reaction (nested RT-PCR) , and analyzed the identity and conducted
      phylogenetic tree by the seqences. RESULTS: The positive rate of GCRV was 16.65%.
      Porcine GCRV strains of Lulong had significant homology differences. Phylogenetic
      analysis indicated porcine GCRVs were with significant diversity. Amino acid
      analysis showed GCRV strains with the same host shared the nearest kinship.
      CONCLUSION: The infection rate of GCRV was high from 2007 to 2008 in Lulong.
      Homology and phylogenetic analysis showed that VP6 gene diversity was widespread.
      The experimental data provided basis for molecular characteristics of porcine
      GCRVs.

PMID- 24319946
TI  - [Molecular and epidemiological study of human adenovirus among infants with
      diarrhea in Nanjing].
AB  - OBJECTIVE: To study the prevalence, clinic features and epidemiologic
      characteristics of human adenovirus diarrhea in Nanjing. METHODS: 730 stool
      specimens were collected from children with diarrhea in Nanjing Children's
      Hospital of Nanjing Medical University from June 2009 to June 2011. Polymerase
      chain reaction (PCR) was employed to detect human adenovirus. The total positive
      PCR products were typed by nest-PCR or multiple PCR. RESULTS: 21 samples (21/730)
      were positive for human adenovirus of all 730 samples from June 2009 to June 2011
      and enteric HAdV-41 is the predominant stain. CONCLUSION: Enteric HAdV-41 and non
      enteric adenovirus were the major etiological agents of viral diarrhea among
      infants and children in Nanjing from 2009 to 2011. We should take the long-term
      systematic surveillance seriously.

PMID- 24319947
TI  - [Sero-epidemiological analysis for entervirus 71 infection of adults in Beijing].
AB  - OBJECTIVE: To evaluate the enterovirus 71 (EV 71) protective antibody level of
      health adults people in Beijing. METHODS: Serum samples and information of
      participants were collected from hospitals in Beijing. EV71 IgG was tested by
      enzyme-linked immunoadsordent assay (ELISA). EV 71 neutralization antibody was
      evaluated by micro-cytopathic effect neutralization test (MCPENT). RESULTS: 486
      participants were enrolled. Age range was 19-62 years old. The average EV 71 IgG
      positive rate was 40. 3% , there are no significant difference between the EV 71
      IgG positive rate of male and female. The rate of EV 71 neutralization antibody
      which title high than 1:256 is 13.3%. The rate of EV 71 IgG and the titile of EV
      71 neutralization antibody are decreasing by the age. CONCLUSION: 40% of health
      adults of Beijing area have EV71 protective antibody. But the title higher than
      1:256 is only 13.3%. EV 71 protective antibody decreases significantly with the
      age.

PMID- 24319948
TI  - [The correlation study of HBV serological index in neonate's venus, cord blood
      and mother's venus blood].
AB  - OBJECTIVE: In this study, we discussed the consistency and correlation of HBV
      serological indexes between neonates' venous blood and cord blood whose mothers
      had chronical HBV infection, as well as the correlation of thoses indexes with
      the mothers'. METHOD: Chronically HBV infected mothers who were postive of both
      HBsAg and HBeAg and also had a HBV DNA virus load above 10(5) copies/ ml and
      their infants were enrolled. The mothers' venous blood were collected before
      delivery. The neonates' cord blood were collected at birth after removal of
      contaminants and disinfected with alcohol on the cord's surface, and the venous
      blood were collected before hepatitis B virus immune globin(HBIG) and hepatitis B
      vaccine were given. The levels of HBsAg, anti-HBs, HBeAg and anti-HBeAg were
      tested with Abbott microparticle chemiluminescence method (Abbott Laboratories,
      Abbott Architac i2000). HBV DNA quantification were tested by COBAS TagMan real
      time PCR Assay. RESULTS: 383 mothers and their infants were enrolled. The
      positive rates of HBsAg in cord blood and venous blood were 61.2% and 63.9%. The
      positive rates of HBeAg level in cord blood and venous blood were 83.2% and
      83.5%. The positive rates of HBV DNA level in cord blood and venous blood were
      56.0% and 59.4%. The state of HBsAg, HBeAg and HBV DNA in cord blood and venous
      blood were consistency, and significant correlation was observed in their levels
      with correlation coefficients of 0.766, 0.857, and 0.692, respectively (P <
      0.000). Significant correlation of the HBeAg levels were observed between
      mothers' venous blood and neonates' venous blood, as well as neonates' cord blood
      with correlation coefficients of 0.362 and 0.352 (P < 0.000). However, there was
      no significant correlation of HBsAg levels between them (r = 0.023, P = 0.785; r
      = 0.04, P = 0.604). CONCLUSIONS: The HBV serological index of neonate's cord
      blood could reflect the HBV serological indexes in venous blood because of the
      good correlation and consistency between them.

PMID- 24319949
TI  - [Selection pressure analysis of H3N2 influenza virus from China between 1992 and
      2012].
AB  - OBJECTIVE: In order to investigate the relationship between selection pressure
      and the prevalence of antigenic clusters, we sequenced and analyzed the H3N2
      influenza virus from China between 1992 and 2012. METHODS: The H3N2 influenza
      virus (n = 1206) in China from 1992 to 2012 was analyzed, include global
      selection pressure and sites positive selection pressure analysis. RESULTS:
      Considering all the H3N2 influenza viruses during these 21 years, a total of four
      amino acid sites subject to positive selection. The global selection pressure
      varies with the variation of different antigenic clusters and three years with
      peak bottom selection pressure were identified. CONCLUSION: The global selection
      pressure rise from the peak bottom, a new antigenic clusters will appear
      andprevalent in the population, indicating the best time to replace the vaccine
      strain.

PMID- 24319950
TI  - [Full sequence analysis and characterization of the Shenzhen Norovirus strain
      SZ2010422].
AB  - OBJECTIVE: To obtain information on viral molecular structural and evolutionary
      characteristics, we conducted the SZ2010422 full-length genomic analysis.
      METHODS: Primers were designed by New Orleans full sequence, SZ2010422 full
      genome was amplified by RT-PCR, the whole genome sequence and the capsid domain
      amino acid sites was analysised after cloned and sequenced. RESULTS: The genome
      of G II-4 Norovirus SZ2010422 strain was consist of 7559 bp, it revealed three
      ORFs composites of the whole genome, ORF1 (5100 bp), ORF2 (1623 bp), ORF3 (807
      bp) respectively, ORF1 and ORF2 had 19 nucleotide overlap. By evolutionary
      comparative analysis found SZ2010422 genomic nucleotide sequences with reference
      strains of G II-4 New Orleans1805 strains the highest homology with a total
      length of homology was 99.3%, of ORF1 (99.5%), ORF2 (99.2%), ORF3 (98.6%).
      Phylogenetic analyses showed SZ2010422 belonging to G II-4 New Orleans variant.
      Date of 541 amino acid analyses showed: New Orleans variant strains of popular
      sites: aa310N or K, --> S aa341D --> of N, aa359T--> S, aa396H --> P, aa460H -->
      Y. CONCLUSION: Norovirus SZ2010422 belonged to the G II-4 New Orleans variant. In
      This study, SZ2010422 full sequence can be used not only as a full-length NoV
      variant sequence standard for future comparison studies, but also as useful
      material for the public health field by enabling the diagnosis, vaccine
      development, and prediction of new emerging variants. Noroviruses; Genes;
      Sequence analysis

PMID- 24319951
TI  - [Genetic characterization of G II.12 norovirus in Beijing from 2008 to 2009].
AB  - OBJECTIVE: To reveal the genetic characteristics of GII.12 Norovirus strains
      isolating from stool samples of adults with diarrhea in Beijing during 2008-2009.
      METHODS: RdRp, ORF2, ORF3 and ORF1/ORF2 overlap region were respectively
      amplified by primers using RT-PCR. The products were purified, cloned, sequenced
      and then aligned, phylogenetic and recombinant analyzed by softwares of DNAStar,
      MEGA and SimPlot. RESULTS: According to the phylogenetic analysis, 11 strains
      belonged to G II.g in the RdRp region,while GII.12 in the ORF2 and ORF3. SimPlot
      analysis further confirmed the 11 strains were recombinant strains ( G II.g
      [RdRp]/G II.12 [capsid]). CONCLUSION: G II.12 Norovirus prevailing in Beijing and
      other regions of the world belonged to the same strain, and we identified the
      genetic characteristics of G II.12 Norovirus in Beijing.

PMID- 24319952
TI  - [Evolutionary and transmission characteristics of rabies viruses in Asia].
AB  - OBJECTIVE: To understand the rabies virus (RABV) evolutionary relationship
      between the strains of China and Asia and to know the evolution and transmission
      characteristics of RABV in Asia. METHODS: The G sequences of representative
      strains from China were selected and combined the sequences of other countries in
      Asia to analyze using BEAST and MigraPhyla software. RESULTS: The phylogenetic
      analysis showed that six groups (China I-VI) of China had different epidemic
      range: China I , II and V groups just cycled in our country; China VI group, from
      Guangxi and Yunnan provinces, crossed with Southeast Asian strains; China III
      group and IV group also have closer genetic relationship with Asian country
      strains. CONCLUSION: Geographic migration in Asia showed that Thailand and India
      may be two rabies transmission centers in Asia.

PMID- 24319953
TI  - [The expression of interferon-lambda1 in CHO cell].
AB  - OBJECTIVE: To construct the eukaryotic expression vector PCI-dhfr-lambda1 and PCI
      dhfr-SP163-lambda1 which linked the enhancer SP163 with interferon lambda1. Then
      express the interferon lambda1 in CHO (dhfr-) cells. METHODS: Using PCR method to
      introduce the restriction enzyme sites and through the fusion PCR binding the
      enhancer with the interferon Lambda1. After sequenced, lambda1 and SP163-lambda1
      was inserted into PCI-dhfr forming the expression vector PCI-dhfr-lambda1 and PCI
      dhfr-SP163-lambda1 which was constructed successfully confirming by sequencing.
      Then the expressing vectors were transfected into CHO (dhfr-) cells using
      liposome transfection method and interferon lambda1 protein was assayed with
      indirect immunofluorescence and Western Blot. Using cytopathic effect inhibition
      evaluated the antiviral activity of interferon lambda1. RESULTS: Successfully
      constructing the eukaryotic expression vectors of interferon lambda and the
      vectors could express interferon lambda1. The result of immunofluorescence showed
      the enhancer developed the expression of interferon lambda1. Detecting the
      interferon lambda1 in CHO (dhfr-) cells after transfecting 48 hour using Western
      Blot. The cytopathic effect inhibition showed the expressed interferon lambda1
      has the antiviral activity. CONCLUSION: Successfully expressed the interferon
      lambda1 in CHO (dhfr-) cells and the protein possesses antiviral activity, which
      may supply a valuable basis for building the stable cell line of interferon
      lambda1.

PMID- 24319954
TI  - [HBV genotype and liver histology effect of peginterferon alpha treatment of
      HBeAg-position chronic hepatitis B].
AB  - OBJECTIVE: To investigate the efficacy of PEG-interferon alpha (PEG-IFN alpha)
      treatment of HBeAg-positive chronic hepatitis B and HBV genotypes and liver
      tissues effect of HBeAg seroconversion. METHODS: 54 cases confirmed by liver
      biopsy, genotype clear HBeAg positive chronic hepatitis B (CHB) patients
      according to body weight, respectively, subcutaneous injection of PEG-IFN-alpha2a
      135 microg or 180 microg, or PEG-IFN-alpha2b 50 microg, 80 microg or 100 microg
      once weekly treatment for 48 weeks and followed for 24 weeks after
      discontinuation. Statistics of HBeAg seroconvertion, HBV genoty pes and liver
      histology e antigen seroconversion after the end of treatment. RESULTS: 54
      patients were followed up at the end of HBeAg seroconversion rate was 29.63%
      (16/54). Genotype B patients with HBeAg seroconversion rate was 35.29%, 27.03%
      higher than the C-type patients, but the difference was not statistically
      significant (chi2 = 0.382, P = 0.537). Inflammation of the liver activity highter
      ( > G2) , the degree of fibrosis heavier ( > S1) HBeAg seroconversion rate
      (50.00% vs. 25.00%, 40.90% vs. 21.88%), but were not statistically significant
      (chi2 = 1.391, 1.444, P = 0.238, 0.229). Activity of HBV genotype, liver
      inflammation, liver fibrosis and other factors by multivariate Logistic
      regression analysis, only liver inflammation activity of the important factors of
      HBeAg seroconversion. CONCLUSION: Important factors, liver inflammation activity
      of PEG-interferon alpha treatment of HBeAg-position chronic hepatitis B patients
      and HBV genotypes and liver fibrosis may be of little significance.

PMID- 24319955
TI  - [The therapeutic effects of pegasys in chronic hepatitis B patients with low
      level ALT].
AB  - OBJECTIVE: To observe the therapeutic effects of Pegasys (pegylated interferon
      alpha-2a) in chronic hepatitis B (CHB) patients with low-level alanine
      transaminase (ALT) < 2 x upper limit of normal (ULN). METHODS: One hundred and
      seven CHB patients were randomized enrolled including 52 with ALT < 2 x ULN and
      liver tissues inflammation activity > or = G2 as observational group and 55 with
      ALT > 2 x ULN as control group. All the enrolled patients received pegasys
      treatment for 48 weeks and the responses between two groups were compared.
      Measurement data were analyzed using t test and numeration data were analyzed
      using chi square test. RESULTS: The reductions of HBV DNA in observational group
      at different time points were all less than control group (all P < 0.05). At the
      end of treatment, the HBV DNA negative rate, HBeAg seroconversion rate and HBsAg
      loss rate in the observational group were 51.9%, 48.8% and 1.9% , respectively,
      which were all lower than control group (67.3% , 66.7% and 7. 3% , respectivley)
      ( all P <0. 05). The ALT normalization rates of two groups were 75% and 76.4% (P
      > 0. 05). CONCLUSION: Pegasys is efficient for CHB patients with ALT < 2 x ULN
      and liver tissues inflammation activity > or = G2, while it is still inferior to
      those with ALT > 2 x ULN.

PMID- 24319956
TI  - [Assessment of healthy related quality of life in patients with HBV induced liver
      cirrhosis].
AB  - OBJECTIVE: To assess healthy related quality of life in patients with HBV induced
      liver cirrhosis. METHODS: A total of 103 cases of patients with HBV induced liver
      cirrhosis were recruited from shenzhen Third People's Hospital during January
      2009 to January 2012. The health related quality of life were assess using the
      most commonly used SF-36 scale questionnaire in all 103 patiemts. Sixty patients
      were further chosen for health related quality assessment using qualitive
      research method. RESULTS: The quality of life of chronic hepatitis B patients
      with cirrhosis Child classification, four score of each group general health,
      vitality, social functioning, mental health was statistically significant (P <
      0.05). Depth interviews found that the disease affects the psychological burden
      of the social needs of the three major affect quality of life factors.
      CONCLUSION: Qualitative research with the SF-36 scale associated to a better
      understanding of the needs of life of patients with chronic hepatitis B
      cirrhosis, provide a reference for subsequent targeted medical services.

PMID- 24319957
TI  - [To explore the safety testing evaluation index of breast-feeding by hepatitis B
      positive mothers].
AB  - OBJECTIVE: To explore the safety testing evaluation index of breast-feeding by
      hepatitis B-positive mothers. METHODS: HBV DNA from serum and breast milk of 252
      hepatitis B-positive mothers were detected with the real-time quantitative PCR.
      RESULTS: The total positive rate of HBV DNA in serum had no difference with that
      in breast milk in hepatitis B-positive mothers (P > 0.05). The positive rate of
      HBV DNA in serum and breast milk of positive HBeAg were significantly higher than
      that of hepatitis B-positive mothers with negative HBeAg (P < 0.01). CONCLUSION:
      To detecte HBeAg and HBV DNA in serum and breast milk have important significance
      for guiding of breast feeding of hepatitis B-positive mothers.

PMID- 24319958
TI  - [Dynamic analysis of the lymphocyte subsets in HCV children with different
      genotypes during treatment].
AB  - OBJECTIVE: To discuss the changes of lymphocyte subsets in HCV children with
      different genotypes during treatment with pegylated interferon alfa-2b and
      ribavirin. METHODS: The genotype of 45 HCV infected children were identified by
      real time PCR. The lymphocyte subsets were dynamically detected by BD FACSCalibur
      flow cytometer with four color MultiTEST IMK Kit during the treatment. RESULTS:
      For the children with 1b genotype, after 24 weeks, the CD4+ T cells were higher
      than pre-treatment (P < 0.05). For the children with 2a genotype, after 12 weeks
      and after 24 weeks, the CD3+ T cells and CD4+ T cells significantly increased
      while the NK cells decreased than pre-treatment (P < 0.05). CONCLUSIONS: The
      lymphocyte subsets of HCV children with 2a genotype were different from 1b
      genotype during trentment with pegylated interferon alfa-2b and ribavirin.

PMID- 24319959
TI  - [Analysis of 11 cases of mycoplasma pneumoniae infection combined with Kawasaki
      disease].
AB  - OBJECTIVE: To study the clinical characteristics of pediatric Kawasaki disease
      complicating mycoplasma pneumoniae pneumonia. METHODS: Retrospective analysis was
      conducted on 11 children who had been diagnosed with Kawasaki disease with
      Mycoplasma pneumoniae pneumonia. RESULTS: The 11 cases presented with varying
      degrees of fever, conjunctival congestion, skin rashes, lymphadenectasis, distal
      extremities lesions, heart and lung lesions. 8 of them were standartly treated
      with azithromycin, while 3 of them were treatad with azithromycin and
      erythromycin. 2 patients with pleural effusion complicated by lobar pneumonia
      consolidation were treated with gamma globulin combined aspirin. All of the 11
      patients were healed. CONCLUSION: Infections are common at the diagonosis of KD.
      Reasonable examination and antibiotics is useful to cure KD with MPP.

PMID- 24319960
TI  - [The treatment effect of immunoglobulin in AIDS with Guillain-Barre syndrome].
AB  - OBJECTIVE: To discuss the treatment effect of immunoglobulin in acquired immune
      deficiency syndrome (AIDS) with Guillain-Barre syndrome (GBS). METHODS: The
      clinical data of AIDS with GBS, diagnosed by clinical and laboratory methods,
      were retrospectively analyzed, and literature retrieval analyzed. RESULTS: After
      treatment by immunoglobulin and antiviral. The patient's peripheral nerve injury
      recovered, and the number of HIV decreased. CONCLUSION: Immunoglobulin has a
      therapeutic effect for HIV infection related GBS, and beneficial to antiviral
      treatment.

PMID- 24319961
TI  - [Value of high risk human papilloma virus detection in screening and diagnosing
      cervical lesion in littoral of Zhejiang province].
AB  - OBJECTIVE: To analyse the infection of high-risk human papiliomavirus (HR-HPV) in
      cervical lesion wome, and evaluate the significance of high-risk human
      pappilomavirus detection by hybrid capture II (HV-II) in screening and diagnosing
      cervical lesion, especially high grade cervical intraepithelial neoplasia (CIN).
      METHODS: A series of 1130 patients of cervical lesion were preliminarily
      diagnosed by cervical cytological examination, HR-HPV detection by HC-II ,
      colposcopy and biopsy under the colposcopy between June 2009 and December 2008,
      including 212 CIN I and (or) condyloma (CIN I/HPV I), 442 CIN II/III, 28 invasive
      cervical cancer. cervical cytological examination is by thin prep liquid-based
      cytology test(TCT),and HR-HPV detection is by HC-II. RESULTS: In 1130 cases the
      positive of HR-HPV was 65.84% (744/1130). Unusual cytology result were 862 cases,
      with 356 ASCUS, 84 ASCH, 216 LSIL, 184HSIL and 22 cancer. The number of biopsy >
      or = CINI/HPVI was 682, positive rate of HR-HPV was 78.59% (536/682). In
      screening CIN II or above, sensitivity, specificity, PPV and NPV of TCT were
      88.94%, 32.73%, 48.49%, 80.60%, of HR-HPV DNA detectiort by HC-II were 90.21%,
      51.82%, 57.14%, 88.14%, and of HR-HPV detection combined with cytology were
      97.45%, 22.42%, 47.22%, 92.50%. CONCLUSION: The infection rate of HR-HPV in
      cervical lesions is higher in each age group. Infection rate of HR-HPV is
      ascending with serious degree of cervical lesion. HR-HPV detection by HC- II is
      an important method in screening cervical lesion. HR-HPV detection is a viable
      option in the management of women with ASCUS and LSIL of TCT, with higher
      sensitivity and NPV.

PMID- 24319963
TI  - [A novel SELEX method for screening of HIV-1 P24 antigen].
AB  - OBJECTIVE: To screen aptamers that can bind P24 antigen tightly and specificly,
      and verify its specificity and affinity. METHODS: Polycarbonate PCR plate was
      coated with P24 antigen and SELEX technology was used to screen aptamer on the
      PCR plate. The primary and secondary structure of these aptamers was analyzed by
      software. Through HRP labeled streptavidin and biotin labeled aptamers, the
      affinity and specificity of obtained aptamers were verified by ELISA. RESULTS:
      The polycarbonate PCR plate could be coated with P24 antigen. Electrophoretic
      analysis showed the aptamers had been enriched. Sequence aligment analysis showed
      that these aptamers have consensus sequence and their apatial structure was
      multiple; ELISA verified that aptamers had high affinity with P24 antigen.
      CONCLUSION: A simple method was established for screening aptamers that can bind
      HIV-1 P24 antigen specificly and tightly.

PMID- 24319962
TI  - [A double antibody sandwich ELISA based assay for titration of severe fever with
      thrombocytopenia syndrome virus].
AB  - OBJECTIVE: To develop an assay for titration of severe fever with
      thrombocytopenia syndrome virus (SFTSV) based on double antibody sandwich ELISA.
      METHODS: A double antibody sandwich ELISA was developed for detection of SFTSV
      based on SFTSV nucleocapsid (N) protein specific poly- and monoclonal antibodies,
      procedures were optimized and evaluated. This ELISA based titration assay was
      compared with fluorescence assasy and plaque assay based titration method.
      RESULTS: The results suggested that the titers obtained by ELISA based method are
      consistent with those obtained by IFA based method (R = 0.999) and the plaque
      assay titration method (R = 0.949). CONCLUSION: The novel ELISA based titration
      method with high sensitivity and specificity is easy to manage and perform, and
      can overcome the subjectivity associated with result determination of the
      fluorescence assay and plaque assay based methods. The novel ELISA based
      titration method can also be applied to high throughput detection.

PMID- 24319964
TI  - [Comparison of ELISA diagnostic kits used in China for hepatitis C virus IgG
      antibody detection].
AB  - OBJECTIVE: To compare the commercial diagnostic reagent available in China for
      hepatitis C virus ( HCV) IgG antibody detection in order to provide some useful
      information for HCV prevention. METHODS: The HCV-IgG detection reagents produced
      by six different Enterprises named A, B, C, D, E and F were chosen and applied to
      detect 160 HCV specious sera samples. HCV-IgG reagent from ABBOTT was adopted as
      gold-standard and the samples in gray zone were determined by RIBA method
      finally. RESULTS: 160 sera samples comprised 88 positive samples and 72 negative
      samples. The total conformity ranged from 88.13% to 98.13% and the Youden indexes
      ranged from 0.74 to 0.96 when the reagents from six different Enterprises were
      compared with gold-standard. The highest conformity was 98.13%, observed in D
      reagent with the highest Youden index of 0.96. CONCLUSION: The total conformity
      rates were more than 88% when the HCV-IgG antibody detection reagents from six
      different Enterprises were compared with ABBOTT reagent. It was highly
      conformable. However, some reagent proved to be less conformable in negative
      samples detection.

PMID- 24319965
TI  - [Development of EV71, CA16 and other enterovirus vrial real-time qualitative PCR
      diagnostic kit].
AB  - OBJECTIVE: A novel multiplex real-time RT-PCR kit was developed to detect EV71,
      CoxA16 and other human enteroviruses simultaneously with an internal
      amplification control to avoids false negatives, which used for hand, foot and
      mouth disease in the clinical diagnosis and epidemiological surveillance.
      METHODS: Design specific primers and probes of EV71, CA16, other intestinal virus
      and internal amplification control, improve the extraction method of virus
      nucleic acid. Optimization the detection system of real-time quantitative PCR.
      Research the products of the accuracy, stability, precision, amplification
      efficiency and detection of linear range. RESULTS: The primers and probes had
      high spicificity. The Viral RNA extraction effect of this Kit is as same as that
      of QIAamp Viral RNA mini Kit (QIAGEN company), but less reagent cost. The optimal
      concentrations of primers and probes are 0.2 micromol/L for all the upstream and
      downstream primers, 0.06 micromol/L for probes of other human enteroviruse, 0.08
      micromol/L for probes of EV71 and CA16 respectively. The kit has good stability,
      accuracy and precision. The amplification efficiencies of EV71, CoxA16 and other
      human enteroviruses are 106% ,101% and 105% and the detection of linear range is
      from 10(9) copies/microl-10(2) copies/microl. CONCLUSION: The novel multiplex
      real-time RT-PCR kit for detecting EV71, CoxA16 and other human enteroviruses
      simultaneously with an internal amplification control has good stability,
      accuracy, precision and amplification efficiencies. So it has great value in
      clinical application.

PMID- 24319966
TI  - [Construction and characterization of EGFP reporter gene labeled Sindbis virus].
AB  - OBJECTIVE: To construct and characterize EGFP reporter gene labeled Sindbis virus
      (SINV). METHODS: The reporter gene EGFP was inserted into the genome of
      infectious clone pBR-XJ160 by using multi-fusion long fragment PCR method. Then
      apply reverse genetic manipulation technique to rescue and obtain EGFP labeled
      SINV. RESULTS: We successively obtained labeled SINV, which has good fluorescent
      expression characteristics and genetic stability. CONCLUSION: The labeled virus
      can be seen in living cells and living body, and this serves as a good tool for
      cell and tissue tropism and biological function study of viruses. This study laid
      a foundation for further studying the cell tropism, biological functions and
      infection mechanism of SINV.

PMID- 24319967
TI  - [Cloning and expressing of tissue inhibitor of metalloproteinases I gene fragment
      and preparation of monoclonal antibodies against the recombinant protein].
AB  - OBJECTIVE: To prepare the monoclonal antibody (mAb) against tissue inhibitor of
      metalloproteinases I (TIMP-I) fusion protein. METHODS: TIMP-I gene was amplified
      from fibrotic human liver tissue by RT-PCR, then ligated with pQE31 to form
      recombinant plasmid pQE-TIMP-I and transformed into E. coli BL21. The protein
      induced by IPTG was purified by 6 x His-tag and used to immunize the BALB/c mice.
      The specific monoclonal antibodies (mAbs) were prepared by the cell fusion
      technique. Western Blot were used to detect specificity of mAbs. RESULTS: The
      prokaryotic plasmid expressing the recombinant protein was constructed, and the
      TIMP-I recombinant protein was expressed and purified. Four hybridoma cell lines
      that secreted anti-TIMP-I mAbs were obtained. 3 of 4 mAbs were the IgG1 subtype.
      Western Blot indicated the mAbs showed specific combination with TIMP-I protein.
      CONCLUSION: The TIMP-I recombinant protein is highly purified and has strong
      antigenicity. The anti- TIMP-I mAbs were prepared successfully.

PMID- 24319968
TI  - [Microbial alpha-amylases: physicochemical properties, substrate specificity and
      domain structure].
AB  - The current literature data on producers, physico-chemical properties and
      substrate specificity of a-amylases produced by microbes from different taxonomic
      groups such as bacteria, fungi and yeasts are discussed in the survey. Synthesis
      of alpha-amylase majority is an inducible process which is stimulated in the
      presence of starch or products of its hydrolysis. It is possible to increase
      enzymes activity level by optimization of cultivation conditions of strains
      producers. alpha-Amylases, isolated from different sources are distinguished in
      their physico-chemical properties, particularly in their molecular weights, pH-
      and thermooptimums, inhibitors and activators. The enzymes hydrolyse soluble
      starch, amylose, amylopectin, glycogen, maltodextrins, alpha- and beta3
      cyclodextrins and other carbohydrate substrates. It is well known that alpha
      amylases belong to GH-13 family of glycosyl-hydrolases, which contain the
      catalytic domain A as (beta/alpha)8-barrel. In addition to domain A, alpha
      amylases contain two other domains: B and C, which are localized approximately on
      opposite sides of (beta/alpha)8-barrel. Most of the known alpha-amylases contain
      calcium ion, which is located on the surface between domains A and B and plays an
      important role in stability and activity of the enzyme.

PMID- 24319969
TI  - [Kinetic properties of calixarene C-90 action on the myometrial plasma membrane
      Ca2+,Mg2+-Atpase activity and on the Ca2+ concentration in unexcited cells of the
      myometrium].
AB  - Plasma membrane Ca2+,Mg2+-ATPase is an important element of general myometrium
      tonus control mechanism, which also makes a contribution to muscle tension
      relaxation after its contraction. Expiriments were done on the myometrial cell
      plasma membrane suspension, which was treated with 0.1% digitonin solution. The
      authors have investigated the inhibitory action of calix[4]arene C-90 (5,11,17,23
      tetra(trifluor) methyl(phenylsulphonylimino)-methylamino-25,26,27,28-tetra
      propoxi-calix[4]arene) on the Ca2+,Mg2+-ATPase activity (the magnitude of 10.5
      was 20.2 +/- 0.5 mkM). The inhibitory action of calix[4]arene C-90 on the
      activity of Ca2+, Mg2+-ATPase is explained as cooperative action of four
      trifluormethyl(phenylsulfonylimino)methylamino groups that are spatially oriented
      on the calix[4]-arene base rather than with the action of tetra-phenol macrocycle
      or separate pharmacophore sulphonilamidin groups. Considering established kinetic
      pattern of calix[4]arene C-90 inhibitory action on the plasma membrane Ca2+,Mg2+
      ATPase activity, stationary kinetical model of basal calcium concentration
      control in unexcited uterus myocytes was developed. It is assumed that obtained
      results may be promising for creation of new generation ("supramolecular")
      pharmacological agent - uterus basal tonus stimulator - on the base of calix[4]
      arene C-90.

PMID- 24319970
TI  - [Ca2+ accumulation study in isolated smooth muscle mitochondria using fluo-4 AM].
AB  - The opportunity of Ca2+-sensitive fluorescent dye Fluo-4 AM and
      spectrofluorimetry method application for the study of energy-dependent Ca2+
      accumulation in mitochondria from uterus smooth muscle is proved. It has been
      found that the presence of mitochondrial preparation increases time-dependent
      fluorescent response considerably and this effect depends on Ca2+ concentration
      in the medium. Thus, in these conditions, deesterification active probe is formed
      which is sensitive to Ca2+. It is shown that the accumulation of calcium ions in
      mitochondria in the presence of Mg-ATP and succinate depends on exogenous Ca2+
      concentration and is characterized by substrate saturating. The apparent
      activation constant of Ca2+ accumulation is 53.9 +/- 6.9 mM, which corresponds to
      the physiological concentration of the cation in the cell next to mitochondria.
      Transit addition of Ca2+-ionophore A23187 to the incubation me- dium caused a
      rapid release of ionized cation from mitochondria. When proton gradient on the
      inner mitochondrial membrane is dissipated by protonophore CCCP, in the case of
      suppressing the generation of the gradient by oligomycin and in the presence of
      ruthenium red that inhibits Ca2+ mitochondrial accumulation systems, Ca2+ entry
      is significantly reduced. The results indicate the prospects of using Fluo-4 AM
      to study the properties of the Ca2+ accumulation system in isolated mitochondria
      of the myometrium.

PMID- 24319971
TI  - [Activity of the glutathione system of antioxidant defense in rats under the
      action of L-glutamic acid].
AB  - The data on the effects of glutamic acid (L-Glu), which is one of three amino
      acid - precursors ofglutathione on animals organism is quite controversial
      because research in this area remain relevant. The aim of our research was to
      find out what impact the additional introduction of L-Glu on the activity
      glutathione system of antioxidant defence and the content of lipid peroxidation
      products in various organs and tissues of rats. The effect of additional (285 and
      715 mg/kg, respectively) introduction to the diet of L-Glu on the activity of
      antioxidant enzymes and intensity of peroxidation processes in various tissues of
      rats was studied. It is shown that in the liver, spleen and kidneys of rats which
      received additional 715 mg/kg of L-Glu content of reduced glutathione and
      glutathione peroxidase activity increased. A decrease of the content of lipid
      hydroperoxides and TBA-active products in tissues of animals which received
      additional 285 and 715 mg/kg of L-Glu into the diet was found. We have also found
      that the enrichment of rat's diet by L-Glu during 30 days resulted in a change of
      glutathione part of antioxidant system and intensity of lipid peroxidation. More
      intensive changes in these indices were observed in animals which received
      additional 715 mg/kg of L-Glu into the diet.

PMID- 24319972
TI  - [Influence of Ca2+ on kinetic parameters of pancreatic acinar mitochondria in
      situ respiration].
AB  - The dependence of respiration rate of rat permeabilized acinar pancreacytes on
      oxidative substrates concentration was studied at various [Ca2+] - 10-8-10-6 M.
      Pancreacytes were permeabilized with 50 microg of digitonin per 1 million cells.
      Respiration rate was measured polarographically using the Clark electrode at
      oxidation of succinate or pyruvate either glutamate in the presence of malate.
      Parameters of Michaelis-Menten equation were calculated by the method of Cornish
      Bowden or using Idi-Hofsti coordinates and parameters of Hill equation - using
      coordinates {v; v/[S]h}. In the studied range of [Ca2+] the kinetic dependence of
      respiration at pyruvate oxidation is described by the Michaelis-Menten equation,
      and at oxidation of succinate or glutamate - by Hill equation with h = 1.11-1.43
      and 0.50-0.85, respectively. The apparent constant of respiration half-activation
      (K0.5) did not significantly change in the studied range of [Ca2+] while at 10-7
      M Ca2+ it was 0.90 +/- 0.06 mM for succinate, 0.096 +/- 0.007 mM for pyruvate and
      0.34 +/- 0.03 mM for glutamate. Maximum respiration rate Vax at pyruvate
      oxidation increased from 0.077 +/- 0.002 to 0.119 +/- 0.002 and 0.140 +/- 0.002
      nmol O2/(s.million cells) due to the increase of [Ca2+] from 10-7 to 5x10-7 or 10
      6 M, respectively. At oxidation of succinate or glutamate Ca2+ did not
      significantly affect Vmax Thus, the increase of [Ca2+] stimulates respiration of
      mitochondria in situ of acinar pancreacytes at oxidation of exogenous pyruvate
      (obviously due to pyruvate dehydrogenase activation), but not at succinate or
      glutamate oxidation.

PMID- 24319973
TI  - [Correlation between basal concentration of C-reactive protein in the blood,
      levels of serum antiendotoxin antibodies and endotoxin-binding capacity of
      monocytes and granulocytes in healthy people].
AB  - The associative links between base concentration of C-reactive protein (hsCRP),
      levels of serum antiendotoxin antibodies of different classes and endotoxin
      binding capacity of monocytes and granulocytes of healthy volunteers were
      investigated by cluster analysis. In the group of healthy volunteers with
      increased base concentration of hsCRP in blood the levels of serum antiendotoxin
      antibodies of different classes and endotoxin-binding capacity of monocytes and
      granulocytes were reduced. Thus, the disbalance of detoxification and clearance
      of endotoxin by humoral and cellular mechanisms can be one of the possible causes
      of development of low intensity inflammation and increase of hsCRP concentration
      in blood.

PMID- 24319974
TI  - [Influence of antihypertensive and metabolic drugs on fatty acids content of
      lipids in cardiomyocytes of rats with spontaneous hypertension].
AB  - Changes in fatty acid composition of lipids are an important factor in the
      development of arterial hypertension. Therefore, this is very important to
      research the role of fatty acid spectrum of the blood and tissues in the
      development of hypertension. The search for effective metabolic drugs and
      antihypertensive drugs which would have the additional ability to influence the
      fatty acid composition of lipids in cells is also important today. We have found
      that hypertensive rats demonstrate the essential decrease of the amount of
      saturated fatty acids (sFA) and high content of unsaturated fatty acids (usFA).
      Application of amlodipine increases the level of sFA compared with animals
      without treatment and the level of usFA tends to decrease. A similar pattern is
      observed when using bisoprolol and combination of amlodipine with bisoprolol,
      although the combination is characterized by more significant changes in FA
      composition of lipids in cardiomyocytes. Treatment with metabolic drug elgacin
      leads to full recovery of saturated and unsaturated fatty acids in the
      cardiomyocytes. During the treatment with combinations of amlodipine with elgacin
      and bisoprolol with elgacin the level of both types of AF was not significantly
      different from the elgacin action in monotherapy. This study demonstrates the
      modification of the FA composition of lipids in cardiomyocytes of the
      spontaneously hypertensive rats. The investigated drugs exhibit a normalizing
      influence on the ratio between sFA and usFA in cardiomyocytes of the hypertensive
      rats.

PMID- 24319975
TI  - [Activity of NAD.H-generating enzymes and cytochrome content in mitochondria from
      rat liver and myocardium under artificial hypobiosis].
AB  - The modification particularities of the structural and functional state of the
      inner mitochondrial membrane of the rat liver and myocardium were observed in
      conditions of artificial hypobiosis, which was created using hypoxic and
      hypercapnic gas medium with a body temperature reduction. Under the artificial
      hypobiosis the activity of NAD.H-generating enzymes of the Krebs cycle of the
      liver mitochondria decreases. The established changes of the enzymes activity and
      cytochromes content of the inner mitochondrial membrane indicate the decrease of
      the oxidative activity of a respiratory chain, that can be limited on a terminal
      (cytochrome c oxidase) site and leads to the decrease (by 49% at an average) of
      the H+-ATPase activity of the liver mitochondria. Under the artificial hypobiosis
      the detected increase of the succinate-KoQ-oxidoreductase activity (by 65% at
      average) causes the maintaining of the functional activity of a mitochondrial
      respiratory chain, considering the high (relative to control) cytochrome c
      oxidase and H+-ATPase activities of the mitochondria of the rats' myocardium. The
      structural changes of the inner mitochondrial membrane of the liver and
      myocardium in experimental conditions are accompanied by the increase of
      hydrophobicity of tryptophan residues microenvironment and the intramolecular
      modifications of protein molecules.

PMID- 24319976
TI  - [Influence of methanol on the content of NAD(P)H, free amino acids and protein in
      the cells of Chlamydomonas reinhartdii].
AB  - It is known that the addition of methanol to the culture medium stimulates the
      photosynthetic productivity of some species of microalgae, but its influence on
      the biochemical composition of the biomass has not been investigated. The aim of
      the present work is to determine the effect of methanol (50 mM) on the content of
      free amino acids, soluble proteins and reduced nicotinamide coenzyme NAD(P)H in
      C. reinhartdii cells. It is shown that in case of illumination of C. reinhardtii
      methanol raises intracellular content of NAD(P)H four times more efficiently than
      in the darkness. Total content of free amino acids is increased and their ratio
      is changed. The concentration of glutamic acid, glutamine, alanine, serine and
      tyrosine also increases. The concentration of valine and methionine is reduced.
      Growth of culture with methanol is followed by an increase in the content of
      intracellular protein by 30% after 20 hours of cultivation. The obtained data
      indicate that methanol stimulates growth of C. reinhardtii, not only as a result
      of additional carbon utilization, but also due to improved nitrogen assimilation
      and the impact on the energy metabolism of cells.

PMID- 24319977
TI  - [Influence of metanandamide on steroidogenesis in rat adrenocorticocytes in
      vitro].
AB  - It is known from literature about antioxidant, anti-inflammatory, membrane
      protective and adreniregulatory properties of N-acetylethanolamines, but data
      concerning their participation in regulation of steroidogenesis are insufficient.
      In order to study the influence of a synthetic analogue of endogenous canabinoid
      anandamide - metanandamide - on the intensity of steroidogenesis the influence of
      different concentrations of the drug on the contents of 11
      hydroxicorticosteroides (11-HCS) in the culture medium after incubation of
      adrenal tissue in rats of both sexes was investigated. The quantitative
      determination of 11-HCS was conducted by fluorometric micromethod. It was shown
      that the incubation of tissue sections with metanandamide leads to a reduction of
      11-HCS in males and an increase of their content in females. It was concluded
      that the inhibition of corticosteroid secretion and synthesis in males may be due
      to reduction of cAMP and inhibition of cAMP-dependent protein kinase A (PKA)
      under the effect of metanandamide. The opposite and dose-dependent effects of the
      preparation in females may be connected with the estrogen influence on the
      mechanisms of drug effect realization.

PMID- 24319978
TI  - [Distribution of 5-fluorouracil between lymphocytes and blood plasma].
AB  - In blood plasma of 8 healthy volunteers with resuspended lymphocytes incubated
      with 5-fluorouracil (5-FU) the drug distribution between cells and liquid was
      assessed by means of HPLC. Rapid accumulation of 5-FU in lymphocytes was proved
      (the drug concentration on the 3-rd minute is 2.5-fold higher than in plasma) as
      well as the absence of temporal changes of 5-FU content both in lymphocytes and
      blood plasma during 30 minutes of experiment.

PMID- 24319979
TI  - [Under what conditions does G.C Watson-Crick DNA base pair acquire all four
      configurations characteristic for A.T Watson-Crick DNA base pair?].
AB  - At the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory it was
      established for the first time, that the Lowdin's G*.C* DNA base pair formed by
      the mutagenic tautomers can acquire, as the A-T Watson-Crick DNA base pair, four
      biologically important configurations, namely: Watson-Crick, reverse Watson
      Crick, Hoogsteen and reverse Hoogsteen. This fact demonstrates rather unexpected
      role of the tautomerisation of the one of the Watson-Crick DNA base pairs, in
      particular, via double proton transfer: exactly the G.C-->G*.C* tautomerisation
      allows to overcome steric hindrances for the implementation of the above
      mentioned configurations. Geometric, electron-topological and energetic
      properties of the H-bonds that stabilise the studied pairs, as well as the
      energetic characteristics of the latters are presented.

PMID- 24319980
TI  - [Structural and energetic properties of the four configurations of the A.T and
      G.C DNA base pairs].
AB  - Using the methods of non-empirical quantum chemistry at the MP2/6
      311++G(2df,pd)// B3LYP/6-311++G(d,p) level of theory it was established for the
      first time, that Hoogsteen, reverse Hoogsteen, Watson-Crick and reverse Watson
      Crick configurations of the A.T and G.C DNA base pairs are isoelectronic and
      isomorphic structures with similar dynamic properties. Based on these results,
      non-ionisation mechanism of the Hoogsteen <"breathing" of the G*.C* DNA base
      pair, namely transformation of the tautomerised (Lowdin's) G-C base pair with
      Watson-Crick geometry into the Hoogsteen electroneutral G*.C* H base pair
      stabilized by the three O6H...N4, N3H...N7 and C8H...02 H-bonds, was postulated.
      It is suggested that such scenario activates only in those cases, when DNA is not
      located in aqueous solution, but works together with proteins and cytosine
      protonation at the N3 atom is precluded.

PMID- 24319981
TI  - [Development and optimization of the methods for determining activity of
      plasminogen activator inhibitor-1 in plasma].
AB  - The activity and content of plasminogen activator inhibitor-1 (PAI-1) are
      important indicators of pathological processes, because its content in plasma
      increases at acute myocardium infarction, tumor, diabetes mellitus, etc. The
      present work is dedicated to the development and optimization of the methods of
      PAI-1 activity definition, which can be used in clinical practice. We have
      proposed the modification of the method COATEST PAI with the usage of chromogenic
      substrate S2251. According to our modification, the cyanogen bromide fragments of
      human fibrinogen have been changed into bovine desAB-fibrin. We have also
      developed the method with the usage of fibrin films. In this method fibrin is
      used as a stimulator of activation reaction and as a substrate at the same time.
      Using fibrin, the native substrate of plasmin, we provide high specificity of the
      reaction and exclude the cross-reaction with other plasma enzymes.

PMID- 24319982
TI  - [Laureates of the Palladin Prize of the National Academy of Sciences of Ukraine
      (1989-1990)].

PMID- 24319983
TI  - Provider attitudes toward oral preexposure prophylaxis for HIV prevention among
      high-risk men who have sex with men in Lima, Peru.
AB  - Oral preexposure prophylaxis (PrEP) was the first biomedical intervention to
      demonstrate efficacy in preventing HIV infection among men who have sex with men
      (MSM). Healthcare providers' attitudes toward PrEP will be critical in
      translating this finding into effective public health rollout programs. In a
      convenience sample of 186 healthcare providers in Peru, we assessed knowledge,
      barriers, and attitudes to prescribe and monitor HIV PrEP for high-risk MSM and
      transgender women, the populations with the highest HIV incidence in this
      setting. A total of 57.5% reported awareness of PrEP, and awareness was
      independently associated with caring for more than 50 MSM (OR: 3.67, p<0.002).
      Lack of local guidelines, concern about increased high-risk behavior,
      antiretroviral drug resistance, and limited availability of antiretrovirals for
      HIV-infected individuals were the most common barriers to prescribing PrEP. Of
      all physicians 44.6% indicated that they would be likely to prescribe oral PrEP
      now; likelihood to prescribe was higher if PrEP were supported by local
      guidelines (70.3%, p<0.001), if more trials supported its effectiveness (68.5%,
      p<0.001), and if intermittent use were shown to be effective (62.2%, p=0.019).
      Physicians were more likely to prescribe PrEP now if they care for more than 50
      MSM (OR: 6.62, p=0.010). Infectious disease specialists were less likely to
      prescribe PrEP (OR: 0.10, p=0.003) than nonspecialists. Successful large-scale
      implementation of PrEP in Peru will require focused educational campaigns to
      increase awareness and address concerns among healthcare providers.

PMID- 24319984
TI  - Vertical convective coassembly of refractory YSZ inverse opals from crystalline
      nanoparticles.
AB  - A facile deposition method of 3D photonic crystals made of yttrium-stabilized
      zirconia (YSZ) was developed. YSZ nanoparticles with primary particle size below
      10 nm and cubic crystalline phase were synthesized by hydrothermal treatment of
      solutions of zirconyl nitrate, yttrium nitrate and acetylacetone. Before
      coassembly with polystyrene (PS) microspheres, a dispersant Dolapix CE64 was
      added to the dialyzed sol of YSZ nanoparticles to render their surface negatively
      charged. Vertical convective coassembly resulted in 3D ordered YSZ/PS hybrid
      films, which were inverted at 500  degrees C in air to produce inverse opals. The
      linear shrinkage of the coatings was in the range 15-20%, below previously
      reported values for YSZ. The obtained coatings demonstrated pronounced photonic
      properties and retained their ordered structure after annealing at 1000  degrees
      C for 2 h. Increasing the filling fraction of crystalline nanoparticles in the
      templates should enable production of fully functional 3D photonic crystals for
      applications in high-temperature photonics. 

PMID- 24319985
TI  - Dissimilatory antimonate reduction and production of antimony trioxide
      microcrystals by a novel microorganism.
AB  - Antimony (Sb) is a metalloid that has been exploited by humans since the
      beginning of modern civilization. The importance of Sb to such diverse industries
      as nanotechnology and health is underscored by the fact that it is currently the
      ninth-most mined metal worldwide. Although its toxicity mirrors that of its Group
      15 neighbor arsenic, its environmental chemistry is very different, and, unlike
      arsenic, relatively little is known about the fate and transport of Sb,
      especially with regard to biologically mediated redox reactions. To further our
      understanding of the interactions between microorganisms and Sb, we have isolated
      a bacterium that is capable of using antimonate [Sb(V)] as a terminal electron
      acceptor for anaerobic respiration, resulting in the precipitation of antimonite
      [Sb(III)] as microcrystals of antimony trioxide. The bacterium, designated strain
      MLFW-2, is a sporulating member of a deeply branching lineage within the order
      Bacillales (phylum Firmicutes). This report provides the first unequivocal
      evidence that a bacterium is capable of conserving energy for growth and
      reproduction from the reduction of antimonate. Moreover, microbiological
      antimonate reduction may serve as a novel route for the production of antimony
      trioxide microcrystals of commercial significance to the nanotechnology industry.

PMID- 24319986
TI  - pH-induced reversible wetting transition between the underwater
      superoleophilicity and superoleophobicity.
AB  - Surfaces with controlled oil wettability in water have great potential for
      numerous underwater applications. In this work, we report a smart surface with pH
      responsive oil wettability. The surface shows superoleophilicity in acidic water
      and superoleophobicity in basic water. Reversible transition between the two
      states can be achieved through alteration of the water pH. Such smart ability of
      the surface is due to the cooperation between the surface chemistry variation and
      hierarchical structures on the surface. Furthermore, we also extended this
      strategy to the copper mesh substrate and realized the selective oil/water
      separation on the as-prepared film. This paper reports a new surface with
      excellently controllable underwater oil wettability, and we believe such a
      surface has a lot of applications, for instance, microfluidic devices,
      bioadhesion, and antifouling materials. 

PMID- 24319987
TI  - Total synthesis of (-)-calyciphylline N.
AB  - The total synthesis of the architecturally complex Daphniphyllum alkaloid (-)
      calyciphylline N has been achieved. Highlights of the synthesis include a Et2AlCl
      promoted, highly stereoselective, susbtrate-controlled intramolecular Diels-Alder
      reaction, a transannular enolate alkylation, an effective Stille
      carbonylation/Nazarov cyclization sequence, and a high-risk diastereoselective
      hydrogenation of a fully substituted conjugated diene ester. 

PMID- 24319988
TI  - Reactive perforating leprosy: pustular erythema nodosum leprosum with epidermal
      perforation and liberation of Mycobacterium leprae.

PMID- 24319989
TI  - A systematic approach to obtain validated partial least square models for
      predicting lipoprotein subclasses from serum NMR spectra.
AB  - A systematic approach is described for building validated PLS models that predict
      cholesterol and triglyceride concentrations in lipoprotein subclasses in fasting
      serum from a normolipidemic, healthy population. The PLS models were built on
      diffusion-edited (1)H NMR spectra and calibrated on HPLC-derived lipoprotein
      subclasses. The PLS models were validated using an independent test set. In
      addition to total VLDL, LDL, and HDL lipoproteins, statistically significant PLS
      models were obtained for 13 subclasses, including 5 VLDLs (particle size 64-31.3
      nm), 4 LDLs (particle size 28.6-20.7 nm) and 4 HDLs (particle size 13.5-9.8 nm).
      The best models were obtained for triglycerides in VLDL (0.82 < Q(2) <0.92) and
      HDL (0.69 < Q(2) <0.79) subclasses and for cholesterol in HDL subclasses (0.68 <
      Q(2) <0.96). Larger variations in the model performance were observed for
      triglycerides in LDL subclasses and cholesterol in VLDL and LDL subclasses. The
      potential of the NMR-PLS model was assessed by comparing the LPD of 52 subjects
      before and after a 4-week treatment with dietary supplements that were
      hypothesized to change blood lipids. The supplements induced significant (p <
      0.001) changes on multiple subclasses, all of which clearly exceeded the
      prediction errors. 

PMID- 24319990
TI  - Total syntheses of the monoterpene indole alkaloids (+/-)-alstilobanine A and E
      and (+/-)-angustilodine.
AB  - A synthetic strategy has been developed culminating in stereoselective total
      syntheses of the small class of unusual monoterpenoid indole alkaloids
      exemplified by alstilobanines A (3) and E (2) and angustilodine (1). A pivotal
      step includes a novel intermolecular Michael-type addition of an indole ester
      dianion to a piperidine-derived nitrosoalkene to form the C15, C16 bond of the
      alkaloids. In addition, an application of the Romo protocol for effecting a
      stereoselective intramolecular nucleophile-assisted aldol-lactonization was
      employed, leading to a beta-lactone incorporating the requisite cis-fused 2
      azadecalin moiety and also setting the C15, C19, C20 relative stereochemistry of
      the metabolites. It was then possible to stereoselectively effect an aldolization
      of a dianion derived from this indole ester beta-lactone intermediate with
      formaldehyde to introduce the requisite C16 hydroxymethyl group. Further
      manipulations of the system ultimately led to the three alkaloids in racemic
      form. 

PMID- 24319991
TI  - Conservative treatment for interstitial monochorionic twin pregnancy: case report
      and review of the published work.
AB  - Interstitial pregnancy is considered one of the most hazardous types of ectopic
      pregnancies, with a mortality rate of 2-2.5%. We describe a case of a viable
      monochorionic twin pregnancy in a 35-year-old woman successfully treated with
      systemic methotrexate associated with bilateral uterine arteries' embolization.
      beta-hCG was undetectable 67 days after the first administration of methotrexate
      and the ultrasonography performed on day 67 showed the remnant of the gestational
      sac in the right uterine horn, a thin endometrium and a normal myometrial
      vascularization. Conservative treatment allowed us to avoid surgical treatment
      and to preserve the patient's fertility. 

PMID- 24319992
TI  - The synergistic effects of fibroblast growth factor-2 and mineral trioxide
      aggregate on an osteogenic accelerator in vitro.
AB  - AIM: To examine the effects of mineral trioxide aggregate (MTA)/fibroblast growth
      factor-2 (FGF-2) on material properties and in vitro human dental pulp cell
      (hDPCs) behaviour. METHODOLOGY: The setting time and diametral tensile strength
      (DTS) of MTA and MTA/FGF-2 were measured. The structure of specimens before and
      after soaking in DMEM was examined under a scanning electron microscope. Alamar
      Blue was used for evaluating hDPCs proliferation. An enzyme-linked immunosorbent
      assay was employed to determine ALP and osteocalcin (OC) expression in hDPCs
      cultured on cements. The effect of small interfering RNA (siRNA) transfection
      targeting fibroblast growth factor receptor (FGFR) was also evaluated. One-way
      analysis of variance was used to evaluate the significance of the differences
      between the mean values. RESULTS: Setting time and DTS data were not found to be
      significant (P > 0.05) between MTA with and without FGF-2. Cell proliferation and
      differentiation increased significantly (P < 0.05) with FGF-2 mixed MTA. After
      siRNA transfection with FGFR, the proliferation and differentiation behaviour of
      the hDPCs appreciably decreased when cultured on an MTA/FGF-2 composite. In
      contrast, no significant amounts (P > 0.05) of ALP and OC were secreted by hDPCs
      seeded on MTA. CONCLUSIONS: Mineral trioxide aggregate with FGF-2 content
      enhanced the higher expression of hDPCs proliferation and osteogenic
      differentiation as compared to pure MTA cement.

PMID- 24319995
TI  - Prediction of shot success for basketball free throws: visual search strategy.
AB  - In ball games, players have to pay close attention to visual information in order
      to predict the movements of both the opponents and the ball. Previous studies
      have indicated that players primarily utilise cues concerning the ball and
      opponents' body motion. The information acquired must be effective for observing
      players to select the subsequent action. The present study evaluated the effects
      of changes in the video replay speed on the spatial visual search strategy and
      ability to predict free throw success. We compared eye movements made while
      observing a basketball free throw by novices and experienced basketball players.
      Correct response rates were close to chance (50%) at all video speeds for the
      novices. The correct response rate of experienced players was significantly above
      chance (and significantly above that of the novices) at the normal speed, but was
      not different from chance at both slow and fast speeds. Experienced players gazed
      more on the lower part of the player's body when viewing a normal speed video
      than the novices. The players likely detected critical visual information to
      predict shot success by properly moving their gaze according to the shooter's
      movements. This pattern did not change when the video speed was decreased, but
      changed when it was increased. These findings suggest that temporal information
      is important for predicting action outcomes and that such outcomes are sensitive
      to video speed.

PMID- 24319993
TI  - Mitochondrial function and energy metabolism in neuronal HT22 cells resistant to
      oxidative stress.
AB  - BACKGROUND AND PURPOSE: The hippocampal cell line HT22 is an excellent model for
      studying the consequences of endogenous oxidative stress. Extracellular glutamate
      depletes cellular glutathione by blocking the glutamate/cystine antiporter system
      xc-. Glutathione depletion induces a well-defined programme of cell death
      characterized by an increase in reactive oxygen species and mitochondrial
      dysfunction. EXPERIMENTAL APPROACH: We compared the mitochondrial shape, the
      abundance of mitochondrial complexes and the mitochondrial respiration of HT22
      cells, selected based on their resistance to glutamate, with those of the
      glutamate-sensitive parental cell line. KEY RESULTS: Glutamate-resistant
      mitochondria were less fragmented and displayed seemingly contradictory features:
      mitochondrial calcium and superoxide were increased while high-resolution
      respirometry suggested a reduction in mitochondrial respiration. This was
      interpreted as a reverse activity of the ATP synthase under oxidative stress,
      leading to hydrolysis of ATP to maintain or even elevate the mitochondrial
      membrane potential, suggesting these cells endure ineffective energy metabolism
      to protect their membrane potential. Glutamate-resistant cells were also
      resistant to oligomycin, an inhibitor of the ATP synthase, but sensitive to
      deoxyglucose, an inhibitor of hexokinases. Exchanging glucose with galactose
      rendered resistant cells 1000-fold more sensitive to oligomycin. These results,
      together with a strong increase in cytosolic hexokinase 1 and 2, a reduced
      lactate production and an increased activity of glucose-6-phosphate
      dehydrogenase, suggest that glutamate-resistant HT22 cells shuttle most available
      glucose towards the hexose monophosphate shunt to increase glutathione recovery.
      CONCLUSIONS AND IMPLICATIONS: These results indicate that mitochondrial and
      metabolic adaptations play an important role in the resistance of cells to
      oxidative stress.

PMID- 24319996
TI  - Clinical relevance of melatonin in ovarian and placental physiology: a review.
AB  - Within the last decade, the synthesis of melatonin in and its functions at the
      level of the peripheral reproductive organs has come into better focus. Melatonin
      is produced at several reproductive organ sites, e.g., the oocyte, ovarian
      follicular cells and the placental cytotrophoblasts. Moreover, these cells also
      contain membrane receptors for this indoleamine. In addition, via the free
      radical scavenging activity of melatonin and its metabolites, oxidative stress is
      reduced in all reproductive organ cells ensuring their optimal function.
      Enhancement of oocyte maturation and preservation of oocyte quality may be major
      functions of melatonin. Oocyte damage reduces successful fertilization and the
      development of a healthy fetus. The findings that melatonin protects the oocyte
      from toxic oxygen species have implications for improving the outcome of in vitro
      fertilization-embryo transfer procedures, as already shown in two published
      reports. Some actions of melatonin in the placenta may be context specific. Thus,
      melatonin is believed to function in the maintenance of optimal placental
      homeostasis by deferring apoptosis of villous cytotrophoblasts, while protecting
      syncytiotrophoblasts from oxidative damage. Melatonin reduces oxidative damage in
      the placenta and may improve hemodynamics and nutrient transfer at the placental
      uterine interface. The use of melatonin to treat preeclampsia should also be
      considered.

PMID- 24319994
TI  - The interaction between eukaryotic initiation factor 1A and eIF5 retains eIF1
      within scanning preinitiation complexes.
AB  - Scanning of the mRNA transcript by the preinitiation complex (PIC) requires a
      panel of eukaryotic initiation factors, which includes eIF1 and eIF1A, the main
      transducers of stringent AUG selection. eIF1A plays an important role in start
      codon recognition; however, its molecular contacts with eIF5 are unknown. Using
      nuclear magnetic resonance, we unveil eIF1A's binding surface on the carboxyl
      terminal domain of eIF5 (eIF5-CTD). We validated this interaction by observing
      that eIF1A does not bind to an eIF5-CTD mutant, altering the revealed eIF1A
      interaction site. We also found that the interaction between eIF1A and eIF5-CTD
      is conserved between humans and yeast. Using glutathione S-transferase pull-down
      assays of purified proteins, we showed that the N-terminal tail (NTT) of eIF1A
      mediates the interaction with eIF5-CTD and eIF1. Genetic evidence indicates that
      overexpressing eIF1 or eIF5 suppresses the slow growth phenotype of eIF1A-NTT
      mutants. These results suggest that the eIF1A-eIF5-CTD interaction during
      scanning PICs contributes to the maintenance of eIF1 within the open PIC. 

PMID- 24319997
TI  - Toward green dialysis: focus on water savings.
AB  - Hemodialysis is one of the most water and energy-hungry medical procedures, and
      thus represents a clear opportunity where improvements should be made concerning
      the consumption and wastage of water. Three levels were investigated on which
      there are potential savings: the precise adjustment of water production according
      to specific needs, the reuse of reverse osmosis rejected water, and finally the
      huge volumes of post-patient dialysate effluent. The "AURAL" (Association pour
      l'Utilisation du Rein Artificiel a Lyon), main unit in Lyon, was the site of
      investigation for this study, which cares for 173 chronic hemodialysis patients.
      Evaluation of the 3 levels described earlier was undertaken on this particular
      building, and on the water treatment currently used. Volumes of produced water
      can be improved by different hydraulic systems or by adjusting the pure water
      conductivity used for dialysis. Concerning the reject water, reuse for building
      sanitation became the focus of further attention. The technical feasibility,
      volume of saved water, and applicable work costs were considered. The results
      suggest that out of a possible 2834 m(3)/year of reject water, 1200 m(3)/year may
      be reused and return on investment recovered within 5.8 years. Finally, the
      reprocessing and feasibility of reuse of dialysate effluent were investigated.
      Initial calculations show that although technical solutions are available, such
      processing of the wastewater production is not profitable in the short term.
      Regarding the significant prior authorization and risk management analysis
      necessary for such a project, this avenue was pursued no further. From the
      perspective of a "green dialysis," the reuse of reject water into sanitation is
      both viable and profitable in our unit, and must be the next step of our project.
      More widely, improvements can be made by defining a more precise range of pure
      water conductivity for dialysis and by applying reuse water project to new or to
      be renovated units.

PMID- 24319998
TI  - Binding patterns and structure-affinity relationships of food azo dyes with
      lysozyme: a multitechnique approach.
AB  - Food dyes serve to beguile consumers: they are often used to imitate the presence
      of healthful, colorful food produce such as fruits and vegetables. But
      considering the hurtful impact of these chemicals on the human body, it is time
      to thoroughly uncover the toxicity of these food dyes at the molecular level. In
      the present contribution, we have examined the molecular reactions of protein
      lysozyme with model food azo compound Color Index (C.I.) Acid Red 2 and its
      analogues C.I. Acid Orange 52, Solvent Yellow 2, and the core structure of
      azobenzene using a combination of biophysical methods at physiological
      conditions. Fluorescence, circular dichroism (CD), time-resolved fluorescence, UV
      vis absorption as well as computer-aided molecular modeling were used to analyze
      food dye affinity, binding mode, energy transfer, and the effects of food dye
      complexation on lysozyme stability and conformation. Fluorescence emission
      spectra indicate complex formation at 10(-5) M dye concentration, and this
      corroborates time-resolved fluorescence results showing the diminution in the
      tryptophan (Trp) fluorescence mainly via a static type (KSV = 1.505 * 10(4) M(
      1)) and Forster energy transfer. Structural analysis displayed the participation
      of several amino acid residues in food dye protein adducts, with hydrogen bonds,
      pi-pi and cation-pi interactions, but the conformation of lysozyme was unchanged
      in the process, as derived from fluorescence emission, far-UV CD, and synchronous
      fluorescence spectra. The overall affinity of food dye is 10(4) M(-1) and there
      exists only one kind of binding domain in protein for food dye. These data are
      consistent with hydrophobic probe 8-anilino-1-naphthalenesulfonic acid (ANS)
      displacement, and molecular modeling manifesting the food dye binding patch was
      near to Trp-62 and Trp-63 residues of lysozyme. On the basis of the computational
      analyses, we determine that the type of substituent on the azobenzene structure
      has a powerful influence on the toxicity of food dyes. Results from this work
      testify that model protein, though an indirect method, provides a more
      comprehensive profile of the essence of toxicity evaluation of food dyes. 

PMID- 24319999
TI  - Fatigue effects on the electromechanical delay components during the relaxation
      phase after isometric contraction.
AB  - AIM: By a combined electromyographic (EMG), mechanomyographic (MMG) and force (F)
      analysis, the electromechanical delay during muscle relaxation (R-DelayTOT ) was
      partitioned into electrochemical and mechanical components. The study aimed to
      evaluate the effects of fatigue on R-DelayTOT components and to assess their
      intersession and interday reliability Intraclass correlation coefficient (ICC).
      METHODS: During tetanic stimulations, EMG, MMG and F were recorded from the human
      gastrocnemius medialis muscle before and after fatigue. The latency between EMG
      and MMG ripple cessations (R-Deltat EMG-MMGR , electrochemical R-DelayTOT
      component); between MMG ripple cessation and F decay onset (R-Deltat MMGR -F,
      first R-DelayTOT mechanical component); and between F decay onset and maximum MMG
      negative peak (R-Deltat F-MMGp-p , second R-DelayTOT mechanical component) was
      calculated. RESULTS: Before fatigue, R-Deltat F-MMGp-p was the major contributor
      (61.9 +/- 1.7 ms, 75%) to R-DelayTOT (82.7 +/- 1.0 ms), while R-Deltat EMG-MMGR
      and R-Deltat MMGR -F accounted for 16% (13.3 +/- 1.2 ms) and 9% (7.5 +/- 1.0 ms)
      respectively. After fatigue, R-DelayTOT , R-Deltat EMG-MMGR and R-Deltat MMGR -F
      increased by 11, 41 and 67%, respectively (P < 0.05), whereas R-Deltat F-MMGp-p
      did not change. Consequently, the relative contribution of R-Deltat EMG-MMGR , R
      Deltat MMGR -F and R-Deltat F-MMGp-p , to R-DelayTOT changed to 20 +/- 2, 12 +/-
      1 and 68 +/- 2% respectively. Measurement reliability was always from high to
      very high (ICC 0.705-0.959). CONCLUSION: Fatigue altered the processes between
      neuromuscular activation cessation and force decay onset, but not the second
      mechanical component (cross-bridges detachment rate and series elastic components
      release). This combined approach provided reliable measurement of the different R
      DelayTOT components and it may represent a valid tool to get more insights on
      muscle electromechanical behaviour.

PMID- 24320000
TI  - Terahertz spectral domain computational analysis of hydration shell of proteins
      with increasingly complex tertiary structure.
AB  - Solvation dynamics of biomolecules and water in a hydration shell have been
      studied by different methods; however, a clear picture of this process is not yet
      established. Terahertz (THz) studies of molecular behavior in binary solutions
      present unique information on the picosecond motions of molecules. A complete
      mechanical interpretation of THz absorption spectra associated with solvated
      biomolecules remains a challenging task. The Gromacs molecular dynamics (MD)
      simulation package is used here to examine the spectral characteristics of water
      molecules in close proximity to biomolecules using vibrational density of states
      (VDOS). Systematic simulation of solvation dynamics of proteins of different size
      and tertiary structure are presented. The following have been selected for
      analysis. They range from less to more complex tertiary structure (corresponding
      to an increased number of secondary structure elements): TRP-cage13-20 peptide,
      TRP-cage, BPTI, and lysozyme. The initial study predicts that the depth of the
      hydration shell, determined by VDOS of water, extends to approximately 10 A and
      does not depend on protein size. Furthermore the integral perturbation
      coefficient of the whole solvation layer is found to be increased for larger
      proteins due to a higher retardation rate of water molecules in their shells.
      Differences in solvation dynamics among the proteins considered originate
      primarily from the water molecules buried in the interior of the protein and not
      from the on-surface molecules. 

PMID- 24320001
TI  - Pharmaceutical and pharmacokinetic characteristics of different types of
      fenofibrate nanocrystals prepared by different bottom-up approaches.
AB  - Low dissolution rate of a poorly water soluble drug often leads to low and
      variable oral bioavailability. Formulating drugs as nanocrystals can help to
      overcome these problems by increasing the solubility and dissolution velocity.
      But different preparation approaches may result in different nanocrystals with
      different characteristics. In this study, three types of fenofibrate nanocrystals
      (FNT-NCs) were prepared by bottom-up methods, antisolvent and thermal
      precipitation under different conditions. These FNT-NCs were characterized by
      scanning electron micrography, dissolution testing, differential scanning
      calorimetry and powder X-ray diffractometry. A significant increase of
      dissolution rate was observed in the drug nanocrystals compared to the crude FNT
      powder (from 20% to 80% in 5 min). The crystallinity of the FNT-NCs prepared by
      antisolvent precipitation increased slightly, while that by thermal precipitation
      decreased. The oral bioavailability of two types of FNT-NCs prepared by
      antisolvent precipitation in rats increased notably compared to that of the crude
      powder (5.5-folds and 5.0-folds, respectively). However, the oral absorption of
      FNT-NCs prepared by thermal precipitation did not increase, although its
      dissolution rate was higher than that of the crude powder. In conclusion,
      different bottom-up methods produce different FNT-NCs with different
      crystallinity, which results in different oral bioavailability. Namely, a careful
      study and rational choice on preparation approaches are significant for the
      nanocrystal techniques.

PMID- 24320002
TI  - Large postauricular defects.

PMID- 24320003
TI  - Detection of ferrocenemethanol and molecular oxygen based on electrogenerated
      chemiluminescence quenching at a bipolar electrode.
AB  - Small molecules, such as ferrocenemethanol (FcMeOH) and O2, that are capable of
      quenching the Ru(bpy)3(2+) excited state via energy or electron transfer can be
      quantitatively detected in a bipolar electrochemical cell based on the
      attenuation of steady-state electrogenerated chemiluminescence (ECL). FcMeOH
      quenches ECL generated by the Ru(bpy)3(2+) oxalate coreactant system, exhibiting
      a linear dependence on [FcMeOH] with a Stern-Volmer slope of 921 M(-1),
      corresponding to a quenching rate constant of 2 * 10(9) M(-1) s(-1). We used the
      bipolar ECL quenching platform to measure dissolved O2 and validated the results
      using a standard Clark electrode. The detection limit for local [O2] measured
      using ECL quenching was found to be 300 ppb. This work opens up the possibility
      of utilizing ECL quenching at bipolar electrodes for a wide range of
      applications. 

PMID- 24320004
TI  - Diagnosing the severity of buccal caries lesions in orthodontic patients at de
      bonding using digital photographs.
AB  - OBJECTIVE: The aims of this study were (1) to evaluate the severity of buccal
      caries lesions according to the International Caries Detection and Assessment
      System (ICDAS) criteria via scoring buccal caries lesions on digital photographs
      at the time of de-bonding and (2) to compare this method with clinical
      examination. MATERIALS AND METHODS: In total, 89 patients treated with upper and
      lower fixed appliances were clinically examined immediately after de-bonding by
      the first author and buccal caries were scored according to the ICDAS-II. Close
      up digital photographs were taken of 245 teeth with different buccal caries
      lesion scores according to the ICDAS-II. Thirteen postgraduate orthodontics
      students independently scored the buccal caries lesions in the digital
      photographs using the modified clinical criteria (ICDAS-II). Intra- and inter
      examiner reliabilities were evaluated by calculating the weighted kappa. To
      evaluate the validity of diagnosing the severity of buccal caries lesions using
      digital photographs compared to clinical examination, Spearman's correlation
      coefficient was calculated. RESULTS: Intra-examiner reliability and the
      reliability between each examiner and the clinical examination showed moderate-to
      excellent agreement, with kappa values of 0.52-0.83. Scoring buccal caries
      lesions via clinical examinations and scoring via photographs were well
      correlated according to the modified ICDAS-II criteria (Spearman's correlation
      coefficient, 0.76). CONCLUSIONS: Thus, scoring buccal caries lesions on digital
      photographs according to ICDAS-II criteria is a reliable and valid method for
      assessing the severity of buccal caries lesions.

PMID- 24320005
TI  - Clinical and neuropathological variability in clinically isolated central nervous
      system Whipple's disease.
AB  - Central nervous system Whipple's disease (CNS-WD) with clinically isolated
      neurological involvement is a rare condition fatal without an early diagnosis. We
      aimed to present clinical and neuropathological features of three cases of pre-
      or post-mortem polymerase chain reaction confirmed CNS-WD with distinct clinical
      presentation, outcome and pathological findings. One patient had an acute onset
      with spinal and brainstem involvement and died without CNS-WD diagnosis after 14
      weeks. Neuropathology showed extensive inflammatory and necrotizing lesions with
      abundant foamy periodic-acid-Schiff (PAS)+ macrophages. The second patient had a
      subacute evolution with late CNS-WD diagnosis and death occurring 18 months after
      onset despite antibiotic treatment. Brain examination showed inflammatory lesions
      in the brainstem, thalamus and cerebellum, and abundant foamy PAS+ macrophages.
      The third case was diagnosed within 4 weeks of onset and treated with an
      excellent response. He died after a disease-free period of 24 months of unrelated
      causes. Neuropathology showed cystic residual lesions devoid of microorganisms
      without inflammatory reaction. CNS-WD may have an acute or subacute course with
      variable response to treatment. Accordingly, subjacent lesions may be those of a
      severe acute necrotizing encephalitic process or subacute inflammatory lesions
      involving diencephalic, brainstem, cerebellar and spinal regions. Chronic,
      cavitary brain lesions may be sequelae of a successful treatment. Early diagnosis
      should allow appropriate treatment and improve prognosis. 

PMID- 24320006
TI  - Histopathological assessment of fatal ipsilateral intraparenchymal hemorrhages
      after the treatment of supraclinoid aneurysms with the Pipeline Embolization
      Device.
AB  - OBJECT: Delayed ipsilateral intraparenchymal hemorrhage has been observed
      following aneurysm treatment with the Pipeline Embolization Device (PED). The
      relationship of this phenomenon to the device and/or procedure remains unclear.
      The authors present the results of histopathological analyses of the brain
      sections from 3 patients in whom fatal ipsilateral intracerebral hemorrhages
      developed several days after uneventful PED treatment of supraclinoid aneurysms.
      METHODS: Microscopic analyses revealed foreign material occluding small vessels
      within the hemorrhagic area in all patients. Further analyses of the embolic
      materials using Fourier transform infrared (FTIR) spectroscopy was conducted on
      specimens from 2 of the 3 patients. Although microscopically identical, the
      quantity of material recovered from the third patient was insufficient for FTIR
      spectroscopy. RESULTS: FTIR spectroscopy showed that the foreign material was
      polyvinylpyrrolidone (PVP), a substance that is commonly used in the coatings of
      interventional devices. CONCLUSIONS: These findings are suggestive of a potential
      association between intraprocedural foreign body emboli and post-PED treatment
      delayed ipsilateral intraparenchymal hemorrhage.

PMID- 24320007
TI  - Learning about the internal structure of categories through classification and
      feature inference.
AB  - Previous research on category learning has found that classification tasks
      produce representations that are skewed toward diagnostic feature dimensions,
      whereas feature inference tasks lead to richer representations of within-category
      structure. Yet, prior studies often measure category knowledge through tasks that
      involve identifying only the typical features of a category. This neglects an
      important aspect of a category's internal structure: how typical and atypical
      features are distributed within a category. The present experiments tested the
      hypothesis that inference learning results in richer knowledge of internal
      category structure than classification learning. We introduced several new
      measures to probe learners' representations of within-category structure.
      Experiment 1 found that participants in the inference condition learned and used
      a wider range of feature dimensions than classification learners. Classification
      learners, however, were more sensitive to the presence of atypical features
      within categories. Experiment 2 provided converging evidence that classification
      learners were more likely to incorporate atypical features into their
      representations. Inference learners were less likely to encode atypical category
      features, even in a "partial inference" condition that focused learners'
      attention on the feature dimensions relevant to classification. Overall, these
      results are contrary to the hypothesis that inference learning produces superior
      knowledge of within-category structure. Although inference learning promoted
      representations that included a broad range of category-typical features,
      classification learning promoted greater sensitivity to the distribution of
      typical and atypical features within categories. 

PMID- 24320008
TI  - Enantioselective oxidation of 1,2-diols with quinine-derived urea organocatalyst.
AB  - Quinine-derived urea has been identified as a highly efficient organocatalyst for
      the enantioselective oxidation of 1,2-diols using bromination reagents as the
      oxidant. This simple procedure utilizes readily available reagents and operates
      at ambient temperature to yield a wide range of alpha-hydroxy ketones in good
      yield (up to 94%) and excellent enantioselectivity (up to 95% ee). 

PMID- 24320009
TI  - Confocal microscopy for healthy and pathological nail.
AB  - Nail diseases are often annoying for the patient and diagnostically challenging
      for dermatologists. New imaging techniques are of high interest in the diagnosis
      of nail disorders to reduce the number of nail biopsies. Confocal microscopy is a
      high-resolution emerging imaging technique that can be used to explore the entire
      body surface, including skin, mucosa, hair and nails. A systematic review of the
      literature concerning the use of confocal microscopy for the study of either
      healthy or pathological nail has been performed to evaluate the current use of
      this technique and possible future applications. Confocal microscopy is
      particularly suitable for nails because it allows a non-invasive in vivo
      examination of this sensitive body area, and nail plate transparency permits to
      image up to the nail bed with an easy identification of corneocytes. Confocal
      microscopy can play a role in the diagnosis of onychomycosis and melanonichia,
      and in the study of drug penetration through the nail plate. It could be used in
      the future as a non-invasive procedure for the investigation of different nail
      diseases, such as psoriasis and lichen planus. Further application could be the
      intra-operative ex vivo examination of nail specimens to outline tumour margins
      to assist surgery. 

PMID- 24320010
TI  - Early timing of endovascular treatment for aneurysmal subarachnoid hemorrhage
      achieves improved outcomes.
AB  - Timing of treatment of aneurysmal subarachnoid hemorrhage has been controversial.
      This retrospective study was designed to access the safety and efficacy among
      cohorts of different timing of endovascular treatment patients with aneurysmal
      subarachnoid hemorrhage. A database of patients with aneurysmal subarachnoid
      hemorrhage was analyzed who were confirmed by CT, and underwent endovascular
      treatment between January 2005 and January 2012,. The patients were grouped into
      four cohorts according to the timing of treatment: ultra-early cohort (within 24
      hours of onset which was confirmed by CT), early cohort (between 24 and 72 hours
      of onset which was confirmed by CT), intermediate cohort (between 4 and 10 days
      of onset which was confirmed by CT) and delayed cohort (after 11 days of onset
      which was confirmed by CT). Patient demographics, aneurysms features and clinical
      outcomes were analyzed to evaluate safety and efficacy for timing of endovascular
      treatment among four cohorts. In our series of 664 patients, 269 patients were
      grouped into ultra-early cohort, 62 patients in early cohort, 218 patients in
      intermediate cohort, and 115 patients in delayed cohort. The patient
      demographics, aneurysm characteristics and neurological conditions on admission
      among groups showed no statistical significance. As a result of the 9-month
      follow-up with 513 patients, good outcome (mRS<2) was achieved in 78% patients in
      "ultra-early" cohort compared with that of 57% in the "intermediate"
      group(p=0.000), whereas other comparisons showed no statistical
      significance(p<0.05) among the four groups. Dividing the patients with
      dichotomized mRS into "good outcome" group and "poor outcome" group (mRS<2) at
      the 9-month follow-up, the results showed lower Hunt-Hess scores (p=0.000) and
      smaller size of aneurysms (p=.001) which were correlated with the good outcome.
      Hypertension (p=0.776), age (p=0.327), sex (p=0.551) and location (p=0.901)
      showed no statistical significance between groups. Endovascular treatment of
      aneurysmal subarachnoid hemorrhage which was confirmed by CT within 72 hours
      achieved better outcomes than that confirmed after 72 hours, especially in those
      patients treated within 24 hours of onset in comparison with patients treated
      between 4 and 10 days.

PMID- 24320011
TI  - Early warning indicators for first-line virologic failure independent of
      adherence measures in a South African urban clinic.
AB  - We sought to develop individual-level Early Warning Indicators (EWI) of virologic
      failure (VF) for clinicians to use during routine care complementing WHO
      population-level EWI. A case-control study was conducted at a Durban clinic.
      Patients after >= 5 months of first-line antiretroviral therapy (ART) were
      defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and
      controls (2:1) if they had VL <= 1000 copies/mL. Pharmacy refills and pill counts
      were used as adherence measures. Participants responded to a questionnaire
      including validated psychosocial and symptom scales. Data were also collected
      from the medical record. Multivariable logistic regression models of VF included
      factors associated with VF (p<0.05) in univariable analyses. We enrolled 158
      cases and 300 controls. In the final multivariable model, male gender, not having
      an active religious faith, practicing unsafe sex, having a family member with
      HIV, not being pleased with the clinic experience, symptoms of depression,
      fatigue, or rash, low CD4 counts, family recommending HIV care, and using a
      TV/radio as ART reminders (compared to mobile phones) were associated with VF
      independent of adherence measures. In this setting, we identified several key
      individual-level EWI associated with VF including novel psychosocial factors
      independent of adherence measures.

PMID- 24320012
TI  - The reproductive health behaviors of HIV-infected young women in the United
      States: A literature review.
AB  - HIV-infected young women in the United States have important reproductive health
      needs that are made more complex by their HIV status. We searched Pubmed and
      relevant bibliographies to identify 32 articles published from 2001 to July 2012
      that described the prevalence, correlates, and characteristics of the sexual
      activity, relationships, pregnancy intentions, HIV status disclosure, and
      contraceptive and condom use among US HIV-infected adolescents and young women.
      Our synthesis of those articles found that, like youth not infected with HIV,
      substantial proportions of HIV-infected youth were sexually active, and most
      sought romantic or sexual relationships, though their serostatus may have
      affected the pace of physical and emotional intimacy. Disclosure was difficult,
      and large proportions of HIV-infected youth had not disclosed their serostatus to
      recent partners. A few studies suggest that most HIV-infected young women hoped
      to have children in the future, but many wanted to avoid pregnancy until later.
      Only one study described contraceptive use among this population in detail and
      found that condoms were a primary method of contraception. The results point to
      substantial gaps in published research, particularly in the areas of pregnancy
      intentions and contraceptive use. Much more needs to be done in research and
      health services to better understand and meet the complex health needs of HIV
      infected young women.

PMID- 24320014
TI  - Prospective cohort study of the impact of antiretroviral therapy on employment
      outcomes among HIV clients in Uganda.
AB  - This study evaluates the impact of antiretroviral treatment (ART) on employment
      related outcomes using prospective, longitudinal analysis. Starting in January
      2008, 602 treatment-naive clients in one rural clinic and in one clinic in the
      capital Kampala were interviewed about their medical history, and psychosocial
      and socioeconomic adjustment at baseline and at months 6 and 12. Half of the
      sample was eligible to receive ART, while the other half was also in HIV care,
      but not yet eligible for ART, therefore providing a comparison group that is
      similar to the treatment group in that its members are HIV-positive and have made
      the decision to enroll in HIV care. We found improvements in general health,
      reduction in the incidence of pain and health interfering with work, as well as
      improvements in work-related self-efficacy for both groups over time, but
      significantly more so for the group receiving ART treatment. At baseline, less
      than half of the people in the ART group worked, but after 6 months more than
      three quarters of them were working, surpassing the fraction of people working in
      the control group after 1 year. Another key finding of the study was the
      importance of mental health as a key mediator for employment-related outcomes.
      These data indicate that ART clients experience greater improvements compared to
      pre-ART clients, and not only with regard to general health, but also in
      restoring confidence in their ability to work, as well as actual work status.

PMID- 24320017
TI  - Identification of ethylene oxide in herbs, spices and other dried vegetables
      imported into Italy.
AB  - Gas chromatography-mass spectrometry was used to analyse ethylene oxide (EO) in
      63 samples of dried vegetable materials for food use derived from import
      commodities and subjected to quality control for three food-transformation
      industries. EO residues were quantified through the determination of ethylene
      chlorohydrin (ECH). About 29% of the samples analysed contained more than 0.3 mg
      kg(-1) of EO. Thus, this specific analytical control limited to 20% of import
      aromatic matters needs to be increased. This paper demonstrates the importance of
      this specific control considering the banned use of microbial decontamination EO
      treatment in the European Union.

PMID- 24320018
TI  - Difference in diet between a general population national representative sample
      and individuals with alcohol use disorders, but not individuals with depressive
      or anxiety disorders.
AB  - BACKGROUND: Mental disorders influence diet and food consumption, but there is a
      lack of consistent findings. AIMS: To investigate food consumption, nutrient
      intakes and serum metabolic biomarkers in depressive, anxiety and alcohol use
      disorders in comparison with the remaining from a population-based nationwide
      sample. METHODS: The study was based on the Health 2000 Survey data of which 5504
      subjects aged 30 and over (3009 women and 2495 men) were used for the analysis.
      Depressive disorder, anxiety disorders and alcohol use disorders were diagnosed
      using the Composite International Diagnostic Interview (M-CIDI). The consumption
      of food and beverage items, and nutrient intakes were measured with a validated
      food frequency questionnaire, and the concentrations of biomarkers were
      determined in blood samples. RESULTS: Overall, no similar differences with both
      genders were found in the intakes of energy, dietary fibre or macronutrients or
      in biomarkers in depressive or anxiety disorders. Women suffering from depressed
      disorder consumed more soft drinks (P = 0.034) and women suffering from anxiety
      disorders consumed more oils (P = 0.001), polyunsaturated fatty acids (P = 0.001)
      and less potatoes (P = 0.002) than the remaining participants. Men suffering from
      depressive disorder consumed less sweets and chocolate (P = 0.001) and men with
      anxiety disorder consumed more tea (P = 0.033) compared with the remaining
      participants. In alcohol use disorders, the intake of carbohydrate was lower in
      both genders (P = 0.001 for women, P = 0.001 for men). CONCLUSIONS: A difference
      in the usual diet exists between individuals with alcohol use disorders and the
      remaining participants on a population level. No consistent difference in both
      genders between those with depressive or anxiety disorders and the remaining was
      found.

PMID- 24320019
TI  - Cluster A personality pathology in social anxiety disorder: a comparison with
      panic disorder.
AB  - BACKGROUND: Social anxiety disorder (SAD) has been associated with cluster A
      personality disorder (PD) traits, mainly paranoid and schizoid traits. AIM: The
      aim of the study was to further investigate cluster A personality pathology in
      patients with SAD. METHODS: Self-reported PD traits were investigated in a
      clinical sample of 161 participants with SAD and in a clinical comparison group
      of 145 participants with panic disorder with or without agoraphobia (PAD).
      RESULTS: A diagnosis of SAD was associated with more paranoid and schizotypal PD
      traits, and an association between depression and personality pathology could
      indicate a state-effect of depression on PD traits. CONCLUSIONS: Patients with
      SAD had more cluster A personality pathology than patients with PAD, with the
      most solid indication for paranoid personality pathology.

PMID- 24320020
TI  - Comparison of patterns and strength of adult attachment in patients with Axis I,
      Axis I+II disorders and a community sample.
AB  - BACKGROUND: Adult attachment patterns influence the quality of close
      relationships, and they are therefore important for treatment planning in
      psychiatry. AIM: This study compares the patterns and strength of adult
      attachment in patients with Axis I, Axis I+II disorders and individuals of a
      general population sample. METHODS: Patients were recruited from a psychiatric
      outpatient clinic, 72 with Axis I disorders and 72 with Axis I+II disorders. The
      patients and a normative community sample (n = 437) filled in the Experiences in
      Close Relationships questionnaire. RESULTS: The proportion of insecure attachment
      differed significantly between all groups: 40% in the community sample, 64% in
      the Axis I group and 90% in the Axis I+II group. On the dimensional anxiety and
      avoidance subscales, a similar significant gradient was observed related to the
      strength of attachment. CONCLUSION: A definite gradient was observed concerning
      patterns and strength of attachment in relation to the severity of
      psychopathology.

PMID- 24320021
TI  - A new patch material for tympanic membrane perforation by trauma: the membrane of
      a hen egg shell.
AB  - CONCLUSION: The egg shell membrane (ESM) patch may promote tympanic membrane (TM)
      healing in acute traumatic TM perforation. OBJECTIVE: To evaluate the use of ESM
      for treating acute traumatic TM perforation. METHODS: We reviewed charts of
      patients with traumatic TM injury from 2008 to 2011. Treatments were an ESM patch
      or a perforation edge approximation. We divided patients into two groups
      according to the treatment used. Each patient was matched by treatment onset and
      perforation size. We compared healing ratio, healing time, and frequency of
      otorrhea between the perforation edge approximation group and the ESM patch
      group. Matched t tests were used for analysis. RESULTS: The healing ratio of the
      TM showed no significant difference between the two groups, but the time to heal
      was significantly shorter in the ESM patch group than in the perforation edge
      approximation group.

PMID- 24320013
TI  - Antiretroviral treatment interruption and loss to follow-up in two HIV cohorts in
      Australia and Asia: implications for 'test and treat' prevention strategy.
AB  - Both antiretroviral treatment interruption (TI) and cessation have been strongly
      discouraged since 2006. We describe the incidence, duration, and risk factors for
      TI and loss-to-follow-up (LTFU) rates across 13 countries. All 4689 adults (76%
      men) in two large HIV cohorts in Australia and Asia commencing combination
      antiretroviral therapy (ART) to March 2010 were included. TI was defined by ART
      cessation >30 days, then recommencement, and loss to follow-up (LTFU) by no visit
      since 31 March 2009 and no record of death. Survival analysis and Poisson
      regression methods were used. With median follow-up of 4.4 years [interquartile
      range (IQR):2.1-6.5], TI incidence was 6.7 per 100 person years (PY) (95% CI:6.1
      7.3) pre-2006, falling to 2.0 (95% CI:1.7-2.2) from 2006 (p<0.01). LTFU incidence
      was 3.5 per 100 PY (95% CI:3.1-3.9) pre-2006, and 4.1 (95% CI:3.5-4.9) from 2006
      (p=0.22). TIs accounted for 6.4% of potential time on ART pre-2006 and 1.2% from
      2006 (p<0.01), and LTFU 4.7% of potential time on ART pre-2006 and 6.6% from 2006
      (p<0.01). Median TI duration was 163 (IQR: 75-391) days pre-2006 and 118 (IQR: 67
      270) days from 2006 (p<0.01). Independent risk factors for the first TI were:
      Australia HIV Observational Database participation; ART initiation pre-2006; ART
      regimens including stavudine and didanosine; three nucleoside analogue reverse
      transcriptase inhibitors; >=7 pills per day; and ART with food restrictions
      (fasting or with food). In conclusion, since 2006, 7.8% of patients had
      significant time off treatment, which has the potential to compromise any 'test
      and treat' policy as during the interruption viral load will rebound and increase
      the risk of transmission.

PMID- 24320022
TI  - Comorbid insomnia in patients with chronic pain: a study based on the Swedish
      quality registry for pain rehabilitation (SQRP).
AB  - PURPOSE: This study investigates the prevalence of insomnia and its relationship
      to other symptoms and health aspects in patients with chronic pain. METHODS:
      Patients with chronic pain conditions (n = 845) referred to a multidisciplinary
      pain centre completed surveys provided by the Swedish quality registry for pain
      rehabilitation (SQRP). The SQRP collects data on socio-demographics, health
      status, symptoms of pain, mood and insomnia and life satisfaction. RESULTS: The
      majority of patients (65.3%) had clinical insomnia according to the insomnia
      severity index (ISI). Insomnia correlated significantly but weakly with pain,
      depression, anxiety and coping; the strongest multivariate correlations were
      found with depression and anxiety followed by pain interference and pain
      severity. Pain intensity, depression and anxiety correlated stronger than ISI
      with respect to the two investigated aspects of health. CONCLUSIONS: The
      prevalence of insomnia is high in patients with chronic pain conditions, but the
      level of importance in relation to other symptoms for health aspects is low, and
      the associations with other important symptoms are relatively weak. One way to
      increase the effects of multimodal rehabilitation programs may be to provide
      interventions directed specifically at insomnia rather than focusing only on
      interventions that address pain, depression and anxiety. Implications for
      Rehabilitation The prevalence of insomnia is high in patients with complex
      chronic pain conditions. Relatively low correlations existed between insomnia and
      pain intensity, depression, anxiety and other psychological aspects. Pain
      intensity, anxiety and depression were more important for perceived health
      aspects than insomnia. One way to increase the effects of multimodal
      rehabilitation programs may be to also include interventions directed directly to
      insomnia.

PMID- 24320023
TI  - An integrated methods study of the experiences of youth with severe disabilities
      in leisure activity settings: the importance of belonging, fun, and control and
      choice.
AB  - PURPOSE: The aim was to examine the leisure activity setting experiences of two
      groups of youth with severe disabilities - those with complex continuing care
      (CCC) needs and those who have little functional speech and communicate using
      augmentative and alternative communication (AAC). METHOD: Twelve youth took part
      in a mixed methods study, in which their experiences were ascertained using
      qualitative methods (observations, photo elicitation and interviews) and the
      measure of Self-Reported Experiences of Activity Settings (SEAS). Data
      integration occurred using a "following a thread" technique and case-by-case
      analysis. RESULTS: The analysis revealed several highly valued aspects of leisure
      activity setting experiences for youth, including engagement with others,
      enjoying the moment, and control and choice in selection and participation in
      activity settings. CONCLUSIONS: The findings provide preliminary insights into
      the nature of optimal activity settings for youth with severe disabilities, and
      the mediators of these experiences. Compared to other youth, the data illustrate
      both the commonalities of experiences and differences in the ways in which these
      experiences are attained. Implications for research concern the utility of mixed
      methods approaches in understanding the complex nature of participation
      experiences. Implications for clinical practice concern the importance of not
      assuming the nature of youths' experiences.

PMID- 24320024
TI  - Disability studies in Sri Lanka: priorities for action.
AB  - PURPOSE: To review the published literature relating to disability in Sri Lanka,
      identify research gaps and inform priorities for action. METHODS: A narrative
      literature review was undertaken and relevant articles extracted using electronic
      databases such as Medline and PubMed. The available literature was examined in
      relation to the nine key recommendations of the World Report on Disability.
      RESULTS: Over the past 30 years, published disability research in Sri Lanka has
      primarily focussed on mental health, visual impairment and healthcare delivery.
      Significant gaps were apparent in evidence relating to the status and services
      for people with intellectual disability, policies and their impact, provider
      attitudes, barriers to education and employment, health workforce training and
      access to healthcare. CONCLUSIONS: While published studies provide insights on
      several dimensions of disability, there are important research gaps pointing to
      unmet needs that require attention to support the health and wellbeing of people
      living with disability in Sri Lanka. To address these gaps, it is imperative that
      a critical mass of multi-disciplinary researchers including people living with
      disabilities collaborate on a strategic program of research using effective
      participatory approaches that engage all sectors and communities relevant to
      uphold the rights of people living with disability. Implications for
      Rehabilitation All nine key recommendations in the World Report on Disability are
      highly pertinent to the needs and status of people living with disabilities in
      Sri Lanka. Significant gaps in research on disability-related health issues exist
      and warrant more focussed attention by researchers, funders and policy makers. It
      is imperative that national stakeholders including the Ministries of Health and
      Social Welfare, organisations representing people living with disability and
      related advocacy groups, work collaboratively to identify and implement a
      research strategy that would better inform disability policies and programmes
      that have access and equity as core principles. Implementation of a national
      disability survey by the Department of Census and Statistics, will help
      prioritize disability research in the country.

PMID- 24320025
TI  - Development of the Spanish version of the Spinal Cord Independence Measure
      version III: cross-cultural adaptation and reliability and validity study.
AB  - PURPOSE: To provide a translation and cross-cultural adaptation of the Spinal
      Cord Independence Measure (SCIM) version III for Spain and to validate the
      Spanish version of the SCIM III (eSCIM III). PATIENTS AND METHODS: Development of
      eSCIM III has involved translation, back-translation and assessment of cultural
      equivalence procedures. eSCIM version III, was administered to 64 patients with
      spinal cord injury, admitted to our hospital. Investigation of the psychometric
      characteristics included: (1) study of the inter-rater reliability, (2) internal
      consistency (Cronbach's alpha), (3) validation and confirmation of the
      correlation between eSCIM III and Functional Independence Measure (FIM), and (4)
      sensitivity to change. RESULTS: The reliability of eSCIM III showed an intra
      class coefficient value >0.97 in the different subscales assessed. Internal
      consistency of eSCIM III was shown by a Cronbach's alpha value of 0.93. The
      validity of eSCIM III was confirmed by the close correlation with FIM (r = 0.94,
      p < 0.0001). The sensitivity to change of eSCIM III was also confirmed.
      CONCLUSIONS: eSCIM III was found to be culturally equivalent to the original
      version, as reliability and validity of this tool were demonstrated. It can be
      used in Spain for functional assessment of patients with spinal cord injury.

PMID- 24320026
TI  - Ipsilateral cerebral hemorrhage following deployment of the Pipeline Embolization
      Device.

PMID- 24320027
TI  - Implementing psychophysiology in clinical assessments of adolescent social
      anxiety: use of rater judgments based on graphical representations of
      psychophysiology.
AB  - Social stressor tasks induce adolescents' social distress as indexed by low-cost
      psychophysiological methods. Unknown is how to incorporate these methods within
      clinical assessments. Having assessors judge graphical depictions of
      psychophysiological data may facilitate detections of data patterns that may be
      difficult to identify using judgments about numerical depictions of
      psychophysiological data. Specifically, the Chernoff Face method involves
      graphically representing data using features on the human face (eyes, nose,
      mouth, and face shape). This method capitalizes on humans' abilities to discern
      subtle variations in facial features. Using adolescent heart rate norms and
      Chernoff Faces, we illustrated a method for implementing psychophysiology within
      clinical assessments of adolescent social anxiety. Twenty-two clinic-referred
      adolescents completed a social anxiety self-report and provided
      psychophysiological data using wireless heart rate monitors during a social
      stressor task. We graphically represented participants' psychophysiological data
      and normative adolescent heart rates. For each participant, two undergraduate
      coders made comparative judgments between the dimensions (eyes, nose, mouth, and
      face shape) of two Chernoff Faces. One Chernoff Face represented a participant's
      heart rate within a context (baseline, speech preparation, or speech-giving). The
      second Chernoff Face represented normative heart rate data matched to the
      participant's age. Using Chernoff Faces, coders reliably and accurately
      identified contextual variation in participants' heart rate responses to social
      stress. Further, adolescents' self-reported social anxiety symptoms predicted
      Chernoff Face judgments, and judgments could be differentiated by social stress
      context. Our findings have important implications for implementing
      psychophysiology within clinical assessments of adolescent social anxiety. 

PMID- 24320028
TI  - Bioaccumulation of Nanosilver by Chlamydomonas reinhardtii-nanoparticle or the
      free ion?
AB  - The bioavailability of a small silver nanoparticle (nAg; nominal size of 5 nm
      with a polyacrylate coating) by the green alga C. reinhardtii was investigated in
      order to assess the contributions of Ag(+) and nAg to cellular internalization.
      Upon exposure to nAg, Ag biouptake exceeded what was predicted based upon
      measured Ag(+) concentrations. Indeed, although Ag biouptake was greatly reduced
      when excess cysteine was added to the nAg, it was nonetheless significantly above
      control levels. For both exposures to nAg and Ag(+), expression levels of the
      Copper Transport Protein 2 (CTR2) indicated that Ag biouptake could be attributed
      to the internalization of Ag(+). Exposure to Ag(+) or nAg increased CTR2
      expression, even when cysteine was present with the nAg. Darkfield microscopy
      coupled with hyperspectral imagery showed that the presence of silver
      nanoparticles inside the cells was more likely due to the rereduction of Ag(+)
      than to the internalization of nAg. The weight of evidence indicated that nAg
      increased Ag biouptake by locally increasing the surface concentrations of Ag(+).

PMID- 24320029
TI  - Editorial: Managing the cardiovascular risk associated with the metabolic
      syndrome.

PMID- 24320030
TI  - Beneficial effects of the Mediterranean diet on metabolic syndrome.
AB  - The metabolic syndrome (MetS) represents a cluster of medical disorders, such as
      hyperglycemia, dyslipidemia, hypertension, and abdominal obesity that, when
      occurring together, increase the risk of developing cardiovascular disease. The
      role of food and nutrients in the aetiology of chronic diseases has become
      clearer over the last 15 years. In this review we collected evidence on the
      beneficial impact of the Mediterranean diet on MetS by analyzing epidemiological
      reports documenting its prevalence in subjects who have adopted this dietary
      pattern. We also explored the role of the individual components of the diet on
      the specific aspects characterizing the MetS (i.e. metabolic indices, body weight
      and blood pressure). There is ample evidence showing that subjects adherent to
      the Mediterranean diet have lower prevalence and incidence rates of MetS than non
      adherent. Moreover, it has been widely documented that specific components of
      this dietary pattern play a role in the prevention of several morbid conditions
      related to the MetS.

PMID- 24320031
TI  - Pharmacologic therapy for cardiovascular risk reduction in patients with the
      metabolic syndrome.
AB  - The metabolic syndrome (MetS) is associated with a higher risk for both, type 2
      diabetes mellitus and cardiovascular disease. The cornerstone of treatment is
      lifestyle modification, encompassing weight reduction and physical exercise.
      However, pharmacotherapy is usually also required to achieve the recommended
      target values for the various components of the MetS, such as hypertension,
      dysglycemia and dyslipidemia. Regarding lipid treatment, statins are the main
      therapeutic agents while in blood pressure control a significant amount of
      pathophysiological and clinical evidence would suggest the use, as first line
      agents, of ACE inhibitors or angiotensin receptor blockers. Metformin seems to be
      the drug of choice for dysglycemia, specially since recent evidence questions the
      safety of thiazolidinediones. New drugs, targeting multiple components of the
      MetS, are under development but no data are currently available regarding their
      long-term efficacy and safety profile. In general, a multifactorial approach is
      recommended to decrease cardiovascular risk in patients with the MetS.

PMID- 24320032
TI  - The metabolic syndrome and chronic liver disease.
AB  - The prevalence of the metabolic syndrome (MetS), a cluster of cardiovascular risk
      factors associated with obesity and insulin resistance, is dramatically
      increasing in Western and developing countries. This disorder is not only
      associated with a higher risk of appearance of type 2 diabetes and cardiovascular
      events, but impacts on the liver in different ways. Nonalcoholic fatty liver
      disease (NAFLD) is considered the hepatic manifestation of MetS, and is
      characterized by triglyceride accumulation and a variable degree of hepatic
      injury, inflammation, and repair. In the presence of significant hepatocellular
      injury and inflammation, the picture is defined 'nonalcoholic steatohepatitis'
      (NASH), that has the potential to progress to advanced fibrosis and cirrhosis.
      Diagnosis of NASH is based on a liver biopsy, and active search for noninvasive
      tests is ongoing. Progression of steatohepatitis to advanced fibrosis or
      cirrhosis has been shown in at least one third of patients followed with paired
      biopsies. Presence of NASH is associated with lower life expectancy, both due to
      liver-related death and to an increase in cardiovascular events. The appearance
      of NAFLD is mainly dependent on increased flow of fatty acids derived from an
      excess of lipolysis from insulin-resistant adipose tissue. Development of NASH is
      based on lipotoxicity and is influenced by signals derived from outside the liver
      and from intrahepatic activation of inflammatory and fibrogenic pathways. The
      presence of the MetS is also associated with worse outcomes in patients with
      cirrhosis due to any causes, and has complex interactions with hepatitis C virus
      infection. Moreover, MetS poses a higher risk of development of hepatocellular
      carcinoma, not necessarily through the development of NASH-related cirrhosis. In
      conclusion, the presence of metabolic alterations has a severe and multifaceted
      impact on the liver, and is responsible for a higher risk of liver-dependent and 
      independent mortality.

PMID- 24320033
TI  - Cell-free nucleic acids as a non-invasive route for investigating
      atherosclerosis.
AB  - Metabolic syndrome is directly linked with atherosclerotic burden and cell-free
      nucleic acids (cf-NA) analysis has recently emerged as a novel research tool in
      atherosclerosis practice and research. cf-NA are nucleic acids (DNA, mRNA, miRNA,
      mitochondrial DNA) found in plasma and cell-free fractions of various other
      biological fluids. They have all the characteristics of the nucleic acids in the
      cells of their origin, thus constituting an emerging field for non-invasive
      assessment. Initially, quantitative and qualitative analysis of cf-NA has been
      accepted as clinically useful in non-invasive prenatal diagnosis, and in the
      diagnosis and monitoring of numerous cancers. As to atherosclerosis, cf-NA
      analysis poses an important challenge in diagnosis and prognostic evaluation of
      acute coronary syndrome, in prediction of cardiovascular disease, in non-invasive
      early detection of atherosclerosis and understanding its pathological mechanism
      in vivo, in assessing various issues of treatment for atherosclerosis in vivo,
      and in the unique simultaneous measurement of mRNA levels and protein
      concentrations in a single sample of plasma. Examples of its use are presented in
      this review. Besides the advances in technologies, the precise evaluation and
      optimization of pre-analytical and analytical aspects of cf-NA analysis have
      impacted importantly on the reliability of test results. We have, therefore,
      reviewed the most important analytical considerations. Further clinical studies
      and analytical improvements will answer the question as to whether cf-NA, as
      novel biomarkers, can be reliably applied clinically in non-invasive, early
      diagnosis and monitoring of the vulnerable atherosclerotic plaques of patients
      who could suffer from acute coronary syndrome. 

PMID- 24320034
TI  - The metabolic syndrome and HIV infection.
AB  - The metabolic syndrome (MetS), a cluster of risk factors for cardiovascular
      disease and type 2 diabetes, has become an important public health problem.
      Considerable differences in the prevalence of the MetS in human immunodeficiency
      virus (HIV)-infected subjects have been reported, as a consequence of several
      limitations regarding the diagnostic critera for MetS. New evidence suggests that
      the use of optimal waist cut-off points specific for the various ethnic
      populations could represent a step forward in overcoming these limitations. Also
      the use of specific cut-off points for measuring upper trunk fat as an adjunctive
      criterion of MetS in HIV patients with lipodystrophy could represent an
      interesting new research topic. Although metabolic disorders have been associated
      indirectly with highly active antiretroviral therapy (HAART), directly with HIV
      infection per se or with host conditions, current circumstances could change the
      framework of MetS in the HIV setting: For example, the aging HIV population and
      newer, less metabolically toxic antiretroviral drugs. Lipotoxicity and adipokines
      have been focused as key issues for explaining MetS in HIV patients. Several
      studies have investigated the pathophysiology of MetS and cardiovascular
      complications in HIV infection. Evidence shows that both HIV infection per se and
      HIV-related chronic immune activation despite antiretroviral therapy are critical
      factors linking MetS and cardiovascular complications. Current epidemiological
      and pathogenetic data on MetS in HIV infection, prevention strategies and
      therapeutic options for all MetS components are reviewed in the light of the
      recent Adult Treatment Panel IV recommendations and the new antiretroviral drugs.

PMID- 24320035
TI  - The role of the heme oxygenase system in the metabolic syndrome.
AB  - Molecular chaperones and the heat shock response play a major role in the
      maintenance of cellular homeostasis under various pathological conditions. In
      particular, their role is to regulate protein conformation, protect proteins from
      misfolding and aggregation, and maintain signalling and organellarnetworks. Among
      variousheat shock proteins, Hsp32 also known as heme oxygenase-1 (HO-1), has
      demonstrated an important role in metabolic syndrome. In particular, the HO
      system seems to play a major role in the complex pathophysiological cascade
      involved in insulin resistance mechanisms, and adipocyte functions as measured by
      the release of important adipokynes. The aim of the present review is to point
      out the role of HO-1 in metabolic syndrome, and how to exploit its beneficial
      effects as a therapeutic strategy to prevent complicationsof andto improve
      insulin sensitivity.

PMID- 24320036
TI  - Resistin: an inflammatory cytokine. Role in cardiovascular diseases, diabetes and
      the metabolic syndrome.
AB  - Resistin is an adipocyte- and monocyte-derived cytokine which has been implicated
      in the modulation of insulin action, energy, glucose and lipid homeostasis.
      Resistin has been associated with insulin resistance and many of its known
      complications. As a molecular link between metabolic signals, inflammation, and
      vascular dysfunction, resistin can be proposed as playing a significant role in
      the heightened inflammatory state induced by metabolic stress linked to excessive
      caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type
      2 diabetes (T2DM), and cardiovascular diseases (CVD). In this review, we
      highlighted the role of resistin, as an inflammatory cytokine, in the development
      of CVD, T2DM and the MetS.

PMID- 24320037
TI  - Incretin-based therapies, glucometabolic health and endovascular inflammation.
AB  - Incretin peptides are a group of gastrointestinal hormones that play a prominent
      role in the regulation of glucose metabolism. Incretin-based therapies (IBTs)
      have recently emerged as an important treatment option for patients with type 2
      diabetes mellitus (T2DM). These pharmaceutical agents may be specially well
      suited for patients who are overweight or obese with primarily post-meal glucose
      peaks, and in whom traditional first-line oral agents have failed to maintain
      adequate glycemic control. There are 2 classes of IBTs: the dipeptidyl peptidase
      4 (DPP-4) inhibitors and the glucagon-like peptide 1 (GLP-1) receptor agonists.
      The ultimate effect of both types of agents is to augment GLP-1 signaling, which
      results in enhanced glucose-dependent insulin secretion, inhibition of glucagon
      secretion and decreased appetite. This leads to improved regulation of glucose
      homeostasis accompanied by either no increase in body weight (with DPP-4
      inhibitors) or a reduction (with GLP-1 receptor agonists). GLP-1 inhibits food
      intake and the increased GLP-1 response may contribute as a satiety signal.
      Although data regarding the effect of GLP-1 agonists and DPP-4 inhibitors on
      levels of peptides involved in the regulation of food intake in T2DM are few, an
      indirect effect of IBT on weight loss is possible (e.g. Exendin-4 induces
      adiponectin secretion in vitro). Results from animal models indicate reduction of
      food intake and body weight by GLP-1 agonists, but follow-up studies are
      required. A growing amount of evidence suggests that these peptides may also
      impact the cardiovascular system, including beneficial effects on myocardial
      cells, lipid profiles and blood pressure as well as reduced markers of systemic
      inflammation and improved endothelial dysfunction. The potential role of these
      agents in improving components of the metabolic syndrome and retardation of
      atherosclerosis needs to be fully elucidated. Although IBTs are currently
      recommended only for use in the early treatment of T2DM, the 'non-glycemic'
      actions of these drugs may have far reaching therapeutic implications. It is
      hoped that future studies will elucidate their potential strengths and weaknesses
      for use in various metabolic conditions.

PMID- 24320038
TI  - Metabolic syndrome and non-cardiac vascular diseases: an update from human
      studies.
AB  - The metabolic syndrome (MetS) is characterized by a cluster of risk factors
      including central obesity, hypertension, dyslipidemia and insulin resistance, The
      MetS is associated with an increased risk for cardiovascular disease (CVD) and
      type 2 diabetes mellitus (T2DM). Several international organizations have defined
      MetS using different diagnostic criteria that produced discrepancies in the
      results of previous studies, thus leading to the latest Joint Interim Societies
      (JIS) MetS definition. Other risk factors than the diagnostic criteria that have
      been associated with MetS include lipid abnormalities, uric acid, liver function,
      prothrombotic factors, cytokines, adipokines, vitamin D, arterial stiffness,
      polycystic ovary syndrome and obstructive sleep apnea. Apart from CVD and T2DM,
      MetS has been related to non-cardiac vascular diseases and in particular to
      stroke, carotid artery disease, peripheral artery disease, chronic kidney
      disease, atherosclerotic renal artery stenosis and abdominal aortic aneurysms. In
      this narrative review, the associations of these diseases with MetS and its
      components will be discussed. These associations may further increase CVD risk in
      MetS patients, highlighting the importance of treating such high-risk individuals
      early and "to target". In this context, multifactorial treatment including a
      statin has been proven beneficial, and thus should be considered, in MetS
      patients.

PMID- 24320039
TI  - Successful treatment of scrotal verruciform xanthoma with shave debulking and
      fractionated carbon dioxide laser therapy.

PMID- 24320040
TI  - Prevalence of periradicular periodontitis in a Scottish subpopulation found on
      CBCT images.
AB  - AIM: To investigate the prevalence of periradicular periodontitis (PRP) using
      cone-beam computed tomography (CBCT) scans in a retrospective cross-sectional
      epidemiological study in a Scottish subpopulation. METHODOLOGY: Of the 319 CBCT
      scans performed at Dundee Dental Hospital between November 2009 and July 2012,
      245 dentate scans of patients over 18 years of age were included and 3595 teeth
      examined. Odds ratios were calculated, and the association between root filling
      and posts with PRP was determined. RESULTS: Radiological signs of PRP were
      detected in 209 teeth (5.8%) in 96 patients (male = 53, female = 43) of which 145
      (69.4%) were measurable and 64 (30.6%) appeared as periapical widening. Most
      lesions were seen in the 46-55-year age group and in maxillary anterior teeth
      (35.4%); 47.4% (n = 81) of the total root filled teeth (n = 171) had PRP. Of the
      root filled teeth with lesions, approximately half (50.6%) had an inadequate root
      filling. Teeth with crowns, but not root filled, accounted for 17.7% of PRP.
      Periapical changes were detected on a high proportion of teeth with post-retained
      crowns (70.7%). The presence of a root filling was significantly associated with
      PRP (z = 17.689 P < 0.0001; odds ratio 16.36 < 23.17 < 32.83, 95% CI) and the
      presence of a post (z = 10.901 P < 0.0001; odds ratio 21.36 < 41.8021 < 81.78,
      95% CI). CONCLUSIONS: The prevalence of PRP in a Scottish subpopulation was 5.8%.
      The presence of a root filling or a post-retained crown was significantly
      associated with the presence of PRP as determined by CBCT scans. The prevalence
      of periradicular disease in root filled teeth remains high in the Scottish
      population.

PMID- 24320041
TI  - Assessing the safety of co-exposure to food packaging migrants in food and water
      using the maximum cumulative ratio and an established decision tree.
AB  - Food contact materials can release low levels of multiple chemicals (migrants)
      into foods and beverages, to which individuals can be exposed through food
      consumption. This paper investigates the potential for non-carcinogenic effects
      from exposure to multiple migrants using the Cefic Mixtures Ad hoc Team (MIAT)
      decision tree. The purpose of the assessment is to demonstrate how the decision
      tree can be applied to concurrent exposures to multiple migrants using either
      hazard or structural data on the specific components, i.e. based on the
      acceptable daily intake (ADI) or the threshold of toxicological concern. The tree
      was used to assess risks from co-exposure to migrants reported in a study on non
      intentionally added substances (NIAS) eluting from food contact-grade plastic and
      two studies of water bottles: one on organic compounds and the other on ionic
      forms of various elements. The MIAT decision tree assigns co-exposures to
      different risk management groups (I, II, IIIA and IIIB) based on the hazard
      index, and the maximum cumulative ratio (MCR). The predicted co-exposures for all
      examples fell into Group II (low toxicological concern) and had MCR values of 1.3
      and 2.4 (indicating that one or two components drove the majority of the
      mixture's toxicity). MCR values from the study of inorganic ions (126 mixtures)
      ranged from 1.1 to 3.8 for glass and from 1.1 to 5.0 for plastic containers. The
      MCR values indicated that a single compound drove toxicity in 58% of the
      mixtures. MCR values also declined with increases in the hazard index for the
      screening assessments of exposure (suggesting fewer substances contributed as
      risk potential increased). Overall, it can be concluded that the data on co
      exposure to migrants evaluated in these case studies are of low toxicological
      concern and the safety assessment approach described in this paper was shown to
      be a helpful screening tool. 

PMID- 24320042
TI  - Prevalence of celiac disease in Iranian patients with irritable bowel syndrome: a
      cross-sectional study.
AB  - OBJECTIVE: This study was aimed to determine the prevalence of celiac disease
      (CD) in irritable bowel syndrome (IBS) and its subtypes in a group of Iranian
      patients. METHODS: From March 2007 to June 2009, 465 consecutive patients who
      were referred to the gastroenterology clinic of Jundishapur University of Medical
      Sciences and fulfilled the Rome III criteria for IBS were included.
      Immunoglobulin A (IgA) anti-tissue transglutaminase (IgA-tTG) and anti-gliadin
      antibody (AGA) levels were measured. CD was confirmed by gastroduodenoscopy and
      biopsy in patients with abnormal antibodies. RESULTS: Five patients had only
      elevated IgA-tTG, 26 with only elevated AGA, and in 16 patients abnormal results
      for both antibodies were reported. Duodenal biopsies from these 47 patients
      confirmed CD in 13 (2.8%, 95% CI 1.6-4.0%) according to the Marsh criteria. Two
      CD patients had normal IgA-tTG concentrations while only one patient with normal
      AGA was proven to have CD. CD was most prevalent in unsubtyped IBS (4.9%, 95% CI
      1.1-8.7%), followed by mixed IBS (4.7%, 95% CI 0.3-9.1%). In multiple comparison,
      CD was less common in diarrhea-predominant IBS than in unsubtyped IBS, although
      this did not reach statistical significance (1.0% vs. 4.9%, P = 0.057).
      CONCLUSIONS: CD in unsubtyped IBS had a growing trend to be more common than in
      diarrhea-predominant IBS. Evaluation of IBS patients for CD is advisable.

PMID- 24320044
TI  - Regioselective derivatization of C84 by Diels-Alder reactions: applications to
      photovoltaic solar cells and fullerene polymerization.
AB  - Regioselective properties of a D2d-C84 in multistep [4 + 2] cycloadditions and
      the applications of bis-functional C84 derivatives were investigated. Density
      functional calculations demonstrate that an indene-C84 bisadduct is a promising
      electron acceptor in organic solar cells and a C84-bis-anthracene copolymer can
      be utilized as a charge-transfer material. 

PMID- 24320043
TI  - A unique megaplasmid contributes to stress tolerance and pathogenicity of an
      emergent Salmonella enterica serovar Infantis strain.
AB  - Of all known Salmonella enterica serovars, S. Infantis is one of the most
      commonly isolated and has been recently emerging worldwide. To understand the
      recent emergence of S. Infantis in Israel, we performed extensive comparative
      analyses between pre-emergent and the clonal emergent S. Infantis populations. We
      demonstrate the fixation of adaptive mutations in the DNA gyrase (gyrA) and
      nitroreductase (nfsA) genes, conferring resistance to quinolones and nitrofurans,
      respectively, and the carriage of an emergent-specific plasmid, designated pESI.
      This self-transferred episome is a mosaic megaplasmid (~280 kb), which increases
      bacterial tolerance to environmental mercury (mer operon) and oxidative stress,
      and provides further resistance to tetracycline, sulfamethoxazole and
      trimethoprim, most likely due to the presence of tetRA, sulI and dfrA genes
      respectively. Moreover, pESI carries the yersiniabactin siderophore system and
      two novel chaperone-usher fimbriae. In vitro studies established that pESI
      conjugation into a plasmidless S. Infantis strain results in superior biofilm
      formation, adhesion and invasion into avian and mammalian host cells. In vivo
      mouse infections demonstrated higher pathogenicity and increased intestinal
      inflammation caused by an S. Infantis strain harboring pESI compared with the
      plasmidless parental strain. Our results indicate that the presence of pESI that
      was found only in the emergent population of S. Infantis in Israel contributes
      significantly to antimicrobials tolerance and pathogenicity of its carrier. It is
      highly likely that pESI plays a key role in the successful spread of the emergent
      clone that replaced the local S. Infantis community in the short time of only 2-3
      years. 

PMID- 24320045
TI  - Selective synthesis of multisubstituted olefins utilizing gem- and vic
      diborylated vinylsilanes prepared by silylborylation of an alkynylboronate and
      diborylation of alkynylsilanes.
AB  - The synthesis of a series of gem- and vic-diborylated vinylsilanes was
      accomplished via highly selective transition-metal-catalyzed syn-dimetalation to
      the alkynylmetal species. This protocol served as a general synthetic method
      toward regio- and stereodefined multisubstituted olefins. The key steps are the
      diastereoselective Suzuki-Miyaura cross-coupling reactions of gem- and vic
      diborylated vinylsilanes, in which the two boron groups showed discrete
      reactivities to afford diverse precursors of multisubstituted olefins. 

PMID- 24320046
TI  - Relationship between local neuroimmune impairment and diabetic foot: the
      immunocompromised district theory.
AB  - BACKGROUND: Diabetic foot (DF) can be defined as an infection and/or an
      ulceration with or without destruction of deep tissues associated with
      neurological abnormalities and varying degrees of peripheral vascular disease of
      the lower limb in patients with diabetes. Both neuropathy and vascular disease,
      along with the well-known impairment of immune function in patients with
      diabetes, contribute to polymicrobial foot infections, which further aggravate
      the already severe clinical manifestations of diabetes. DISCUSSION: The
      immunocompromised district (ICD) is a novel pathogenic concept referring to a
      site in which there is an obstacle to the normal trafficking of immunocompetent
      cells through lymphatic channels, and/or interference with the signals that
      neuropeptides and neurotransmitters, released by peripheral nerves, send to cell
      membrane receptors of immunocompetent cells. These loci minoris resistentiae have
      the propensity to develop a secondary disease, which may occur after an extremely
      variable length of time. CONCLUSIONS: In this work, we provide an overview of
      etiopathogenetic mechanisms of DF and propose a unifying view of this topic based
      on the concept of the ICD.

PMID- 24320047
TI  - Associated analysis of DNA methylation for cancer detection using CCP-based FRET
      technique.
AB  - This paper describes an associated analysis method of DNA methylation for the
      detection of cancer using an optically amplifying cationic conjugated polymer
      (CCP, poly{(1,4-phenylene)-2,7-[9,9-bis(6'-N,N,N-trimethyl ammonium)-hexyl
      fluorene] dibromide)}. Genomic DNA is digested by methylation-sensitive
      restriction endonuclease, followed by PCR amplification to incorporate
      fluorescein-labeled dNTP. Only methylated DNA can be amplified by PCR, and the
      methylation level is detected through fluorescence resonance energy transfer
      (FRET) between CCP and fluorescein that is incorporated into the PCR product. The
      methylation levels of RASSF1A, OPCML, and HOXA9 promoters of 35 ovarian cancer
      samples and 11 normal samples were assayed. In accordance with the degree of
      methylation levels, they are clustered to three sections and assigned a value.
      Through an associated analysis, we acquired a threshold for cancer detection with
      a sensitivity of 85.7%. The assay takes about 20 h to obtain the detection
      results and shows great potential as a useful tool for diagnostic and screening
      of cancer. 

PMID- 24320049
TI  - Mechanism of N2 reduction to NH3 by aqueous solvated electrons.
AB  - Recently a novel approach to the photocatalytic reduction of molecular nitrogen
      under ambient conditions was reported in which hydrated electrons generated from
      ultraviolet illumination of diamond served as the reducing agent [Zhu, D.; Zhang,
      L.; Ruther, R. E.; Hamers, R. J. Photo-Illuminated Diamond as a Solid-State
      Source of Solvated Electrons in Water for Nitrogen Reduction. Nat. Mater. 2013,
      12, 836-841]. This surprising reduction of N2 by aqueous solvated electrons is
      absent from the vast existing radiolysis literature and thus has little
      mechanistic precedent. In this work, a combination of experimental and
      computational approaches is used to elucidate the detailed molecular-level
      mechanistic pathway from nitrogen to ammonia. A variety of approaches, including
      electronic structure calculations, molecular dynamics simulations, kinetic
      modeling, and pH-dependent experimental measures of NH3 and competing H2
      production, implicate a hydrogen atom addition mechanism at early reduction steps
      and sequential protonation/direct reduction by a solvated electron at later
      steps, thus involving both direct and indirect reactions with solvated electrons.
      This work provides a framework for understanding the possible application of
      solvated electrons as energetic reducing agents for chemically inert species
      under mild conditions.

PMID- 24320048
TI  - Binding interactions between long noncoding RNA HOTAIR and PRC2 proteins.
AB  - Long noncoding RNAs (lncRNAs) play a key role in the epigenetic regulation of
      cells. Many of these lncRNAs function by interacting with histone repressive
      proteins of the Polycomb group (PcG) family, recruiting them to gene loci to
      facilitate silencing. Although there are now many RNAs known to interact with the
      PRC2 complex, little is known about the details of the molecular interactions.
      Here, we show that the PcG protein heterodimer EZH2-EED is necessary and
      sufficient for binding to the lncRNA HOTAIR. We also show that protein
      recognition occurs within a folded 89-mer domain of HOTAIR. This 89-mer
      represents a minimal binding motif, as further deletion of nucleotides results in
      substantial loss of affinity for PRC2. These findings provide molecular insights
      into an important system involved in epigenetic regulation. 

PMID- 24320050
TI  - Toward gene therapy for growth hormone deficiency via salivary gland expression
      of growth hormone.
AB  - OBJECTIVES: Salivary glands are useful targets for gene therapeutics. After gene
      transfer into salivary glands, regulated secretory pathway proteins, such as
      human growth hormone, are secreted into saliva, whereas constitutive secretory
      pathway proteins, such as erythropoietin, are secreted into the bloodstream.
      Secretion of human growth hormone (hGH) into the saliva is not therapeutically
      useful. In this study, we attempted to redirect the secretion of transgenic hGH
      from the saliva to the serum by site-directed mutagenesis. MATERIALS AND METHODS:
      We tested hGH mutants first in vitro with AtT20 cells, a model endocrine cell
      line that exhibits polarized secretion of regulated secretory pathway proteins.
      Selected mutants were further studied in vivo using adenoviral-mediated gene
      transfer to rat submandibular glands. RESULTS: We identified two mutants with
      differences in secretion behavior compared to wild-type hGH. One mutant, DeltaN1
      6 , was detected in the serum of transduced rats, demonstrating that expression
      of this mutant in the salivary gland resulted in its secretion through the
      constitutive secretory pathway. CONCLUSION: This study demonstrates that
      mutagenesis of therapeutic proteins normally destined for the regulated secretory
      pathway may result in their secretion via the constitutive secretory pathway into
      the circulation for potential therapeutic benefit.

PMID- 24320051
TI  - Measuring adhesion forces in powder collectives by inertial detachment.
AB  - One way of measuring adhesion forces in fine powders is to place the particles on
      a surface, retract the surface with a high acceleration, and observe their
      detachment due to their inertia. To induce detachment of micrometer-sized
      particles, an acceleration in the order of 500,000g is required. We developed a
      device in which such high acceleration is provided by a Hopkinson bar and
      measured via laser vibrometry. Using a Hopkinson bar, the fundamental limit of
      mechanically possible accelerations is reached, since higher values cause
      material failure. Particle detachment is detected by optical video microscopy.
      With subsequent automated data evaluation a statistical distribution of adhesion
      forces is obtained. To validate the method, adhesion forces for ensembles of
      single polystyrene and silica particles on a polystyrene coated steel surface
      were measured under ambient conditions. We were able to investigate more than 150
      individual particles in one experiment and obtained adhesion values of particles
      in a diameter range of 3-13 MUm. Measured adhesion forces of small particles
      agreed with values from colloidal probe measurements and theoretical predictions.
      However, we observe a stronger increase of adhesion for particles with a diameter
      larger than roughly 7-10 MUm. We suggest that this discrepancy is caused by
      surface roughness and heterogeneity. Large particles adjust and find a stable
      position on the surface due to their inertia while small particles tend to remain
      at the position of first contact. The new device will be applicable to study a
      broad variety of different particle-surface combinations on a routine basis,
      including strongly cohesive powders like pharmaceutical drugs for treatment of
      lung diseases.

PMID- 24320052
TI  - Third-harmonic generation in ultrathin films of MoS2.
AB  - We observe optical third-harmonic generation in atomically thin films of MoS2 and
      deduce effective third-order nonlinear susceptibilities on the order of 10(-19)
      m(2)/V(2), which is comparable to that of commonly used semiconductors under
      resonant conditions. By measuring the susceptibility as a function of light
      wavelength, we find significant enhancements of the susceptibility by excitonic
      resonances. The demonstrated third-harmonic generation can be used for nonlinear
      optical identification of MoS2 atomic layers with high contrast, better
      distinguishing power of multilayers, and less restrictions to substrate
      selections. The size of the third-order nonlinear susceptibility suggests
      feasibility of exploring other types of third-order nonlinear optical effects of
      MoS2 two-dimensional crystals. 

PMID- 24320055
TI  - Longitudinal effects on mental health of moving to greener and less green urban
      areas.
AB  - Despite growing evidence of public health benefits from urban green space there
      has been little longitudinal analysis. This study used panel data to explore
      three different hypotheses about how moving to greener or less green areas may
      affect mental health over time. The samples were participants in the British
      Household Panel Survey with mental health data (General Health Questionnaire
      scores) for five consecutive years, and who relocated to a different residential
      area between the second and third years (n = 1064; observations = 5320). Fixed
      effects analyses controlled for time-invariant individual level heterogeneity and
      other area and individual level effects. Compared to premove mental health
      scores, individuals who moved to greener areas (n = 594) had significantly better
      mental health in all three postmove years (P = .015; P = .016; P = .008),
      supporting a "shifting baseline" hypothesis. Individuals who moved to less green
      areas (n = 470) showed significantly worse mental health in the year preceding
      the move (P = .031) but returned to baseline in the postmove years. Moving to
      greener urban areas was associated with sustained mental health improvements,
      suggesting that environmental policies to increase urban green space may have
      sustainable public health benefits. 

PMID- 24320053
TI  - Role of 53BP1 in the regulation of DNA double-strand break repair pathway choice.
AB  - The p53-binding protein 1 (53BP1) is a well-known DNA damage response (DDR)
      factor, which is recruited to nuclear structures at the site of DNA damage and
      forms readily visualized ionizing radiation (IR) induced foci. Depletion of 53BP1
      results in cell cycle arrest in G2/M phase as well as genomic instability in
      human as well as mouse cells. Within the DNA damage response mechanism, 53BP1 is
      classified as an adaptor/mediator, required for processing of the DNA damage
      response signal and as a platform for recruitment of other repair factors. More
      recently, specific 53BP1 contributions to DSB repair pathway choice have been
      recognized and are being characterized. In this review, we have summarized recent
      advances in understanding the role of 53BP1 in regulating DNA DSBs repair pathway
      choice, variable diversity joining [V(D)J] recombination and class-switch
      recombination (CSR). 

PMID- 24320054
TI  - Acute and fractionated exposure to high-LET (56)Fe HZE-particle radiation both
      result in similar long-term deficits in adult hippocampal neurogenesis.
AB  - Astronauts on multi-year interplanetary missions will be exposed to a low,
      chronic dose of high-energy, high-charge particles. Studies in rodents show
      acute, nonfractionated exposure to these particles causes brain changes such as
      fewer adult-generated hippocampal neurons and stem cells that may be detrimental
      to cognition and mood regulation and thus compromise mission success. However,
      the influence of a low, chronic dose of these particles on neurogenesis and stem
      cells is unknown. To examine the influence of galactic cosmic radiation on
      neurogenesis, adult-generated stem and progenitor cells in Nestin-CreER(T2)/R26R
      YFP transgenic mice were inducibly labeled to allow fate tracking. Mice were then
      sham exposed or given one acute 100 cGy (56)Fe-particle exposure or five
      fractionated 20 cGy (56)Fe-particle exposures. Adult-generated hippocampal
      neurons and stem cells were quantified 24 h or 3 months later. Both acute and
      fractionated exposure decreased the amount of proliferating cells and immature
      neurons relative to sham exposure. Unexpectedly, neither acute nor fractionated
      exposure decreased the number of adult neural stem cells relative to sham
      expsoure. Our findings show that single and fractionated exposures of (56)Fe
      particle irradiation are similarly detrimental to adult-generated neurons.
      Implications for future missions and ground-based studies in space radiation are
      discussed. 

PMID- 24320056
TI  - Linoleic and alpha linolenic acids ameliorate streptozotocin-induced diabetes in
      mice.
AB  - Streptozotocin (STZ)-induced diabetes in mice progresses with decreased
      desaturase activities and alterations in the metabolism of essential fatty acids
      (EFA). OBJECTIVES: Based on our previous studies with soybean oil that
      ameliorated the STZ damage in mice, we tested here the accountability of its main
      EFA components, i.e. linoleic acid (LA) and alpha linolenic acid (ALA), in the
      prevention of pancreas damage and Delta6 desaturase decrease. MATERIALS AND
      METHODS: Seven days after injection with STZ and EFA gavage, ICR mice were
      sacrificed. Plasma glucose and insulin levels, pancreas histology and liver fatty
      acid desaturases were analysed. RESULTS: EFA reduced pancreas damage, insulin and
      glucose plasma levels and restored Delta6 desaturase activity and mRNA expression
      levels. DISCUSSION: By reducing pancreas damage, EFA ameliorated insulin levels,
      Delta6 desaturase and fatty acid metabolism. LA further enhanced Fads2 promoter
      activity. CONCLUSION: EFA ameliorate STZ induced diabetes in mice.

PMID- 24320057
TI  - The use of sunscreen starting on the first day after ablative fractional skin
      resurfacing.
AB  - BACKGROUND: The most common side-effect of ablative fractional skin resurfacing
      in Asians is post inflammatory hyperpigmentation (PIH). Various attempts have
      been made to reduce the occurrence of PIH after laser treatment including sun
      avoidance, the use of preoperative and postoperative treatment regimens, and
      treatment using conservative energy settings and epidermal protection.
      OBJECTIVES: To determine whether the use of broad-spectrum sunscreen with anti
      inflammatory agents starting on the first day after fractional CO2 laser skin
      resurfacing reduces the incidence of post laser PIH. MATERIALS AND METHODS:
      Thirty patients were treated with ablative fractional CO2 resurfacing on both
      sides of their faces at 10 mJ and 10% density. Each subject was randomly treated
      on one side of the face with petrolatum ointment four times a day for the first
      week after laser treatment and on the other side of the face with petrolatum
      ointment four times a day plus broad-spectrum sunscreen with anti-inflammatory
      agents in the morning starting on the first day after laser treatment.
      Transepidermal water loss was recorded at baseline and every day for 1 week.
      Melanin and erythema indexes were measured at baseline, 1-, 2-week, 1-, 2- and at
      3-month post treatment. RESULTS: Of the 30 patients involved in the study, 26
      received the treatment and attended 1-, 2-week, 1-, 2- and 3-month post-treatment
      visits. Four patients were withdrawn from the study because they could not attend
      every follow-up visit. There was no statistically significant difference in
      transepidermal water loss at baseline, immediately after laser treatment, or at
      the D1 to D7 follow-up visits. Erythema index had no significantly statistical
      difference at baseline, 1-, 2- and at 3-month after laser treatment. Furthermore,
      there was a statistically significant difference in melanin index at 1-week post
      laser treatment between both sides (P = 0.001). Melanin index at the 1-week
      follow-up visit on the side treated with broad-spectrum sunscreen with anti
      inflammatory agents starting on the first day after laser treatment was
      significantly less than the control side. CONCLUSION: The use of broad-spectrum
      sunscreen with anti-inflammatory agents starting on the first day after ablative
      fractional skin resurfacing can decrease the incidence of PIH after laser
      treatment at 1-week postoperatively.

PMID- 24320058
TI  - Prognostic factors and status of hormone receptors and angiogenic factors in
      uterine carcinosarcoma.
AB  - AIM: To determine novel prognostic factors and treatment modalities for uterine
      carcinosarcoma (UCS). METHODS: We performed immunohistochemical staining of
      estrogen receptor (ER)-alpha, ER-beta, progesterone receptor, gonadotropin
      releasing hormone receptor, vascular endothelial growth factor (VEGF), platelet
      derived endothelial cell growth factor (PD-ECGF) and platelet-derived growth
      factor receptor (PDGFR)-beta in a clinicopathological study of 15 UCS patients.
      RESULTS: No significant differences were found between the sarcomatous and
      carcinomatous components with respect to expression of ER-alpha, ER-beta and
      progesterone receptor. However, VEGF was significantly more frequently expressed
      in the carcinomatous component, while PD-ECGF and PDGFR-beta were significantly
      more frequently expressed in the sarcomatous component. Only one patient showed
      gonadotropin-releasing hormone receptor expression in the sarcomatous component.
      Moreover, ER-beta expression in resected specimens, increased serum levels of
      carbohydrate antigen (CA)-125 and C-reactive protein (CRP), and thrombocytosis
      were determined as significant UCS prognostic factors. CONCLUSION: Combination of
      anti-VEGF therapy and anti-PD-ECGF or anti-PDGFR-beta therapy would be expected
      in advanced or recurrent UCS. Furthermore, careful monitoring for early detection
      of recurrence should be performed when UCS patients showed preoperative increase
      in serum CA-125 levels, CRP and platelet counts, and ER-beta expression in
      biopsied or surgically resected specimens.

PMID- 24320059
TI  - Commentary: the endocrown: an alternative approach for restoring extensively
      damaged molars.

PMID- 24320060
TI  - Commentary: the effect of a modeling resin and thermocycling on the surface
      hardness, roughness, and color of different resin composites.

PMID- 24320061
TI  - clinical evaluation of enamel microabrasion for the aesthetic management of mild
      to-severe dental fluorosis.
AB  - STATEMENT OF THE PROBLEM: The clinical performance of enamel microabrasion alone
      for aesthetic management of dental fluorosis is debatable. PURPOSE OF THE STUDY:
      This study aimed to compare the clinical efficacy of enamel microabrasion for the
      aesthetic management of mild-to-severe dental fluorosis. METHODS/MATERIALS: A
      total of 154 fluorosed incisors and canines in 14 patients on the basis of the
      fluorosis were included; the teeth were classified as mild (group I, n = 53),
      moderate (group II, n = 56), and severe (group III, n = 45). All teeth were
      treated with enamel microabrasion (Opalustre, Ultradent Products, South Jordan,
      UT, USA). "Improvement in appearance," "changes in brown stains," "changes in
      opaque white areas," and "requirement for further treatments" were assessed by
      using visual scale systems. The data were analyzed using nonparametric tests
      (alpha = 0.05). RESULTS: The "improvement in appearance" score was the worst for
      group III (p < 0.05), whereas the "changes in opaque white areas" score was the
      best for group I (p < 0.05). Groups II and III did not differ with respect to
      "changes in brown stains." The proportion of patients who needed further
      treatment was the highest in Group III (p < 0.05). CONCLUSIONS: The severity of
      fluorosis affected the clinical performance of enamel microabrasion except for
      its performance of removing brown stains. Increase in fluorosis severity led to
      increased requirements for further treatments. CLINICAL SIGNIFICANCE: The
      clinical performance of enamel microabrasion is affected by the severity of
      dental fluorosis, except for its performance of removing brown stains. Even
      though its performance of improving appearance decreases with the increase in
      severity of fluorosis, it may not only remove the fluorosis stains but also may
      increase the success of additional subsequent treatment.

PMID- 24320062
TI  - Commentary: clinical evaluation of enamel microabrasion for the esthetic
      management of mild-to-severe dental fluorosis.

PMID- 24320063
TI  - Critical appraisal: dental amalgam update--part II: biological effects.
AB  - Dental amalgam restorations have been controversial for over 150 years. In Part I
      of this Critical Appraisal, the clinical efficacy of dental amalgam was updated.
      Here in Part II, the biological effects of dental amalgam are addressed. 

PMID- 24320064
TI  - Improvement of colonic healing by preoperative oral partially hydrolyzed guar gum
      (Benefiber) in rats which underwent preoperative radiotherapy.
AB  - Abstract Background: Neoadjuvant radiotherapy in rectal cancer could interfere
      with anastomotic healing. We investigated the effects of preoperative oral
      administration of Benefiber on the healing irradiated colonic anastomosis.
      Methods: Forty male Wistar rats were divided into four groups. Group I (control
      group), Group II (Benefiber(r) pretreatment group), Group III (preoperative
      radiotherapy group) and Group IV (preoperative radiotherapy and Benefiber(r)
      pretreatment group). All animals underwent 1 cm left colon resection and primary
      anastomosis. On the 3rd and 7th postoperative days, all the rats were
      anesthetized to assess the anastomotic healing clinically, mechanically,
      histologically and biochemically. Results: The mean bursting pressure was
      significantly lower in-group III and significantly higher in-group II on day 7.
      The histologic parameters of anastomotic healing, such as epithelial regeneration
      and formation of granulation tissue, were significantly improved by use of
      preoperative Benefiber(r) on day 7. The amount of acid-soluble collagen
      concentrations significantly increased in-group IV compared to group III on day
      3. The amount of salt-soluble collagen concentrations significantly increased in
      group II compared to group III on day 3. Conclusions: Colonic anastomotic healing
      can be adversely affected by preoperative radiotherapy, but orogastric feeding
      with Benefiber may improve the healing process.

PMID- 24320065
TI  - Moral elevation reduces prejudice against gay men.
AB  - Disgust is linked to social evaluation. People with higher disgust sensitivity
      exhibit more sexual prejudice, and inducing disgust increases sexual prejudice.
      We tested whether inducing moral elevation, the theoretical opposite of disgust,
      would reduce sexual prejudice. In four studies (N = 3622), we induced elevation
      with inspiring videos and then measured sexual prejudice with implicit and
      explicit measures. Compared to control videos that elicited no particular
      affective state, we found that elevation reduced implicit and explicit sexual
      prejudice, albeit very slightly. No effect was observed when the target of social
      evaluation was changed to race (Black-White). Inducing amusement, another
      positive emotion, did not significantly affect sexual prejudice. We conclude that
      elevation weakly but reliably reduces prejudice towards gay men. 

PMID- 24320066
TI  - Reconceptualizing resistance: sociology and the affective dimension of
      resistance.
AB  - This paper re-examines the sociological study of resistance in light of growing
      interest in the concept of affect. Recent claims that we are witness to an
      'affective turn' and calls for a 'new sociological empiricism' sensitive to
      affect indicate an emerging paradigm shift in sociology. Yet, mainstream
      sociological study of resistance tends to have been largely unaffected by this
      shift. To this end, this paper presents a case for the significance of affect as
      a lens by which to approach the study of resistance. My claim is not simply that
      the forms of actions we would normally recognize as resistance have an affective
      dimension. Rather, it is that the theory of affect broadens 'resistance' beyond
      the purview of the two dominant modes of analysis in sociology; namely, the study
      of macropolitical forms, on the one hand, and the micropolitics of everyday
      resistance on the other. This broadened perspective challenges the persistent
      assumption that ideological forms of power and resistance are the most pertinent
      to the contemporary world, suggesting that much power and resistance today is of
      a more affective nature. In making this argument, it is a Deleuzian reading of
      affect that is pursued, which opens up to a level of analysis beyond the common
      understanding of affect as emotion. I argue that an affective approach to
      resistance would pay attention to those barely perceptible transitions in power
      and mobilizations of bodily potential that operate below the conscious
      perceptions and subjective emotions of social actors. These affective transitions
      constitute a new site at which both power and resistance operate. 

PMID- 24320067
TI  - Self, career and nationhood: the contrasting aspirations of British and French
      elite graduates.
AB  - There is increasing interest in the emergence of a 'global middle class' in which
      high achieving young graduates increasingly look to develop careers that
      transcend national boundaries. This paper explores this issue through comparing
      and contrasting the aspirations and orientations of two 'elite' cohorts of
      graduates. Interviews with students at the University of Oxford, England, and
      Sciences-Po, France, reveal very different ambitions and allegiances. Our Oxford
      respondents portray their futures as projects of self-fulfilment as they build
      portfolio careers by moving from job to job and from country to country with
      limited social allegiances - epitomizing the nomadic worker of the transnational
      elite. Our Parisian respondents, on the other hand, display strong allegiances to
      the nation, state and civic duty. Their projects of the self involve reconciling
      their personal aspirations with strong allegiances to France. The paper concludes
      by discussing the significance of these differences. It argues that the enduring
      role of education in the formation of national identities should not be
      overlooked and that more detailed research is needed on the contextual specifity
      of transnationalism and the (re)production of elites. 

PMID- 24320068
TI  - A Christian identity for the liberal state?
AB  - It seems to be impossible for the liberal state to embrace a Christian identity,
      because 'liberalism' is exactly a device for separating state and religion.
      Discussing the implications of a recent decision of the European Court of Human
      Rights, Lautsi v. Italy (2011), I argue that this is not necessarily so. If
      paired with a liberal commitment to pluralism, a Christian identity might even be
      more inclusive of minority religions than a narrowly 'liberal' state identity,
      which has been the dominant response in Western Europe to the challenge of
      immigrant diversity, especially that of Muslim origins. 

PMID- 24320069
TI  - Reifications of the intellectual: representations, organization and agency in
      revolutionary China.
AB  - How did 'intellectuals' evolve from a class of subjects in Marxian thoughts to
      highly visible populations under communism? Such 'reifications of the
      intellectual' have deeply affected subjectivity, conflict and organization, but
      received little attention in the political sociology of communism. This essay
      draws on research on classifications and social boundaries to address the
      objective and subjective foundations of the reifications and their impact on
      communist rule. The intellectual is viewed as an identification formed and
      performed around multiple social axes (most notably family background,
      educational achievement, occupational history, institutional affiliation and
      revolutionary rank) that reflected broader patterns of communist political
      domination. I use the Chinese Communist movement to demonstrate that (1)
      interaction of political contests, ruling strategies and institutional
      developments turned a diversity of persons into 'intellectuals' who were
      allegedly imbued with reprehensible interests and habits linked to privileged
      economic classes; (2) constant competitions for power and organizational changes
      led to classificatory ambiguities and, in turn, allowed individuals some control
      over their identifications; and (3) the developments profoundly influenced
      identity, state and class formation. Focusing on the dynamics that produced a
      highly visible but fluid population of 'intellectuals' opens new pathways for
      comparative research on communism. 

PMID- 24320070
TI  - Class habitus and perception of the future: recession, employment insecurity and
      temporality.
AB  - This paper examines the consequences of the recent economic downturn and UK
      government spending cuts, as exacerbations of prevailing trends in neoliberal
      employment policy, on temporal perception, specifically as it relates to the
      adaptation of subjective anticipations of and projections into the future to
      objective prospects of unemployment by class. Grounded in a phenomenologically
      minded Bourdieusian conceptualization of class and time and contextualized by
      statistics on chances of job loss, it draws on qualitative research with 57
      individuals from across the class structure to chart differing dispositions
      toward the future. In particular, it distinguishes three orientations - the
      future as controllable, the future as uncontrollable and the future as reasonably
      controllable - which appear to correspond with resources possessed. 

PMID- 24320071
TI  - The class-origin wage gap: heterogeneity in education and variations across
      market segments.
AB  - This paper uses unique population-level matched employer-employee data on monthly
      wages to analyse class-origin wage gaps in the Swedish labour market. Education
      is the primary mediator of class origin advantages in the labour market, but
      mobility research often only considers the vertical dimension of education. When
      one uses an unusually detailed measure of education in a horizontal dimension,
      the wage gap between individuals of advantaged and disadvantaged class origin is
      found to be substantial (4-5 per cent), yet considerably smaller than when
      measures are used which only control for level of education and field of study.
      This is also the case for models with class or occupation as outcome. The class
      origin wage gap varies considerably across labour market segments, such as those
      defined by educational levels, fields of education, industries and occupations in
      both seemingly unsystematic and conspicuous ways. The gap is small in the public
      sector, suggesting that bureaucracy may act as a leveller. 

PMID- 24320072
TI  - Class and ideological orientations revisited: an exploration of class-based
      mechanisms.
AB  - Studies of the relationship between class position and political outlooks still
      only have a limited understanding of the class-related mechanisms that matter for
      ideological orientations. This article presents a comprehensive analysis of the
      mechanisms that link class position and left/right and authoritarian/libertarian
      orientations. Besides main factors such as income, career prospects, job
      security, education, class origin and class identification, the significance of
      work-related factors such as work autonomy, working in a team, a physically
      demanding job and a mentally demanding job is studied. The findings are based on
      a survey specifically designed for this purpose and collected in Sweden in
      2008/2009. A great deal of the association between class position and left/right
      orientations is explained by socio-economic conditions; different classes
      sympathize with policies that will benefit them economically. Another important
      factor is class identification. Work-related factors also have relevance, but the
      effect of class position on left/right orientations works mainly through the
      remuneration system. Class position is also related to authoritarian/libertarian
      orientations. However, this relationship is less explained by socio-economic
      position per se, but is rather an effect of the educational system and its
      allocation of the workforce into different class positions. It also turns out
      that work-related factors do not explain the class effects; however, a physically
      demanding job shows a unique effect. Overall, our findings suggest that besides
      factors such as class position, income, education and class identification, we
      need to consider work-related aspects to derive a more complete understanding of
      the distribution of ideological orientations in Western societies. 

PMID- 24320073
TI  - Techno economic systems and excessive consumption: a political economy of
      'pathological' gambling.
AB  - This article argues that gambling is a paradigmatic form of consumption that
      captures the intensified logic at the heart of late modern capitalist societies.
      As well as a site of intensified consumption, it claims that gambling has also
      become the location of what has been described as a new form of 'social
      pathology' related to excess play. Drawing on Castells' (1996) notion of techno
      economic systems, it explores the ways that intersections between technology,
      capital and states have generated the conditions for this situation, and
      critiques the unequal distribution of gambling environments that result. It
      argues that, while the products of these systems are consumed on a global scale,
      the risks associated with them tend to be articulated in bio-psychological
      discourses of 'pathology' which are typical of certain types of knowledge that
      have salience in neo-liberal societies, and which work to conceal wider
      structural relationships. We argue that a deeper understanding of the political
      and cultural economy of gambling environments is necessary, and provide a
      synoptic overview of the conditions upon which gambling expansion is based. This
      perspective highlights parallels with the wider global economy of finance
      capital, as well as the significance of intensified consumption, of which
      gambling is an exemplary instance. It also reveals the existence of a geo
      political dispersal of 'harms', conceived as deteriorations of financial,
      temporal and social relationships, which disproportionately affect vulnerable
      social groups. From this, we urge an understanding of commercial gambling based
      on a critique of the wider social body of gambling environments within techno
      economic systems, rather than the (flawed) individual bodies within them. 

PMID- 24320074
TI  - On the almost inconceivable misunderstandings concerning the subject of value
      free social science.
AB  - A value judgment says what is good or bad, and value-free social science simply
      means social science free of value judgments. Yet many sociologists regard value
      free social science as undesirable or impossible and readily make value judgments
      in the name of sociology. Often they display confusion about such matters as the
      meaning of value-free social science, value judgments internal and external to
      social science, value judgments as a subject of social science, the relevance of
      objectivity for value-free social science, and the difference between the human
      significance of social science and value-free social science. But why so many
      sociologists are so value-involved - and generally so unscientific - is
      sociologically understandable: The closest and most distant subjects attract the
      least scientific ideas. And during the past century sociologists have become
      increasingly close to their human subject. The debate about value-free social
      science is also part of an epistemological counterrevolution of humanists
      (including many sociologists) against the more scientific social scientists who
      invaded and threatened to expropriate the human subject during the past century. 

PMID- 24320075
TI  - Cross-lagged relations among parenting, children's emotion regulation, and
      psychosocial adjustment in early adolescence.
AB  - Numerous studies have reported substantive correlations between indicators of
      parenting, children's emotion regulation (ER), and children's psychosocial
      adjustment. However, studies on underlying mechanisms are scarce. Particularly in
      early adolescence, it is still unclear whether relations between parenting and ER
      are caused by adolescent behavior, by parent behavior, or by reciprocal
      processes. Moreover, it is unclear whether ER can be seen as an antecedent or a
      consequence of psychosocial adjustment. The aim of this study was to examine
      predictive relations among parenting and adolescents' ER, and adolescents' ER and
      psychosocial adjustment, respectively. We collected longitudinal, multiple
      informant data at two measurement occasions (Grade 6, Grade 7). All told, 1,100
      adolescents (10-14 years) and their parents filled out questionnaires assessing
      responsiveness and psychological control, adolescents' anger regulation, and
      adolescents' problem and prosocial behavior. Cross-lagged analyses revealed
      reciprocal effects between parenting, ER, and adjustment for the parent and
      boys', but not for the girls', report. Moreover, relations were different for
      adolescents with versus without clinically elevated symptoms of psychopathology.
      Our findings support the assumption that reciprocal relations between parenting,
      ER, and psychosocial adjustment are likely to persist until early adolescence.
      Nevertheless, the moderating role of gender and psychopathology should be taken
      into account. Possible reasons for the different findings, and practical
      implications, are discussed. 

PMID- 24320076
TI  - Asymmetric conjugate addition to alpha-substituted enones/enolate trapping.
AB  - An NHC-Cu complex catalyzed the asymmetric conjugate addition (ACA) of various
      Grignard reagents to nonactivated alpha-substituted cyclic enones to give 2,3
      dialkylated cyclopentanones and cyclohexanones. The Michael addition features the
      formation of a magnesium enolate intermediate. One-pot diastereoselective
      trapping of this enolate by alkyl, propargyl, allyl, and benzyl halides led to
      ketones with contiguous alpha-quaternary and beta-tertiary centers. 

PMID- 24320077
TI  - Modified locking horizontal mattress suture.

PMID- 24320078
TI  - Ablation of the creA regulator results in amino acid toxicity, temperature
      sensitivity, pleiotropic effects on cellular development and loss of virulence in
      the filamentous fungus Beauveria bassiana.
AB  - For most organisms, carbon and nitrogen uptake are essential for growth,
      development and, where applicable, pathogenesis. The role of the carbon
      catabolite repressor transcription factor homologue BbcreA in the
      entomopathogenic fungus Beauveria bassiana was investigated. Deletion of BbcreA
      resulted in pleiotropic effects, including nutrient toxicity, leading to a novel
      cell lytic phenotype. Fungal growth in rich media and minimal media containing
      select amino acids/peptides was severely compromised, with microscopic
      examination revealing conidial-base germ tube degeneration and cell lysis
      occurring during growth, a phenomenon exacerbated at higher temperatures (32
      degrees C). Depending upon nutrient conditions, growth, pigment and aerial
      mycelium production, sporulation and dimorphic transition to blastospore
      production were also impaired in the DeltaBbcreA strain. Although loss of BbcreA
      resulted in de-repression of secreted protease and lipase, enzymes critical in
      mediating pathogenesis, insect bioassays indicated severe defects in virulence
      using both topical and intra-haemocoel injection assays, with eruption and
      subsequent sporulation on host cadavers greatly reduced in the mutant. These data
      suggest that BbcreA functions as more than a carbon repressor and plays important
      roles in nutrient utilization, cell homeostasis and virulence. In particular,
      BbcreA is required for proper assimilation of select amino acids and peptides,
      including asparagine, arginine and proline. 

PMID- 24320079
TI  - Actinic cheilitis: clinicopathologic profile and association with degree of
      dysplasia.
AB  - BACKGROUND: Actinic cheilitis (AC) is a potentially malignant disorder of the lip
      caused by exposure to solar radiation. OBJECTIVES: This study was conducted to
      evaluate the clinicopathologic profile of cases of AC and to verify associations
      with the degree of dysplasia. METHODS: This retrospective study analyzed data for
      40 patients with AC. Demographic, clinical, and histopathologic data were
      evaluated. Sections measuring 5 MUm in thickness were cut, deparaffinized, and
      stained with hematoxylin and eosin for histologic examination. The degree of
      epithelial dysplasia was graded using the criteria defined by the World Health
      Organization. Two calibrated oral pathologists analyzed the slides. RESULTS:
      Analysis of the AC patients sampled showed that 75.0% were male (P=0.002), 80.0%
      were aged>=40 years (P<0.001), 74.3% were Caucasian (P=0.004), and 68.6% had
      occupational exposure to sunlight (P=0.028). The most common clinical
      manifestation was white lesions (55.0%), and 40.0% of patients had no dysplasia.
      No significant associations emerged between the histologic grading of AC and
      gender (P=1.000), age (P=1.000), ethnicity (P=0.416), occupational exposure to
      sunlight (P=1.000), and clinical presentation (P=0.467). CONCLUSIONS: The degree
      of dysplasia in AC was not statistically associated with gender, age, ethnicity,
      occupational exposure to sunlight, or clinical appearance. This study provides
      some support for the hypothesis that clinicopathologic features are not related
      to the degree of dysplasia in AC.

PMID- 24320080
TI  - Ab initio molecular dynamics simulation of proton hopping in a model polymer
      membrane.
AB  - We report the results of ab initio molecular dynamics simulations of a model
      Nafion polymer membrane initially equilibrated using classical molecular dynamics
      simulations. We studied three hydration levels (lambda) of 3, 9, and 15 H2O/SO3(
      ) corresponding to dry, hydrated, and saturated fuel cell membrane, respectively.
      The barrier for proton transfer from the SO3(-)-H3O(+) contact ion pair to a
      solvent-separated ion pair decreased from 2.3 kcal/mol for lambda = 3 to 0.8
      kcal/mol for lambda = 15. The barrier for proton transfer between two water
      molecules was in the range from 0.7 to 0.8 kcal/mol for the lambda values
      studied. The number of proton shuttling events between a pair of water molecules
      is an order of magnitude more than the number of proton hops across three
      distinct water molecules. The proton diffusion coefficient at lambda = 15 is
      about 0.9 * 10(-5) cm(2)/s, which is in good agreement with experiment and our
      previous quantum hopping molecular dynamics simulations. 

PMID- 24320081
TI  - Polybrominated Diphenyl Ethers (PBDEs) in paired human hair and serum from e
      waste recycling workers: source apportionment of hair PBDEs and relationship
      between hair and serum.
AB  - Human hair has been widely used as a bioindicator for human persistent organic
      pollutants (POPs) exposure, but studies on the sources of hair POPs and the
      relationship between hair and body burden are limited. This study analyzed the
      possible source apportionment of hair PBDEs and examined the relationship between
      PBDE concentrations in paired hair and serum from e-waste recycling workers.
      Using the ratio of BDE 99/47 and BDE 209/207 as indices, we calculated that only
      15% of the highly brominated congeners (nona- and deca-BDE congeners) comes from
      exogenous (external) exposure for both female and male hair, but an average of
      64% and 55% of the lower-brominated congeners (tetra- to penta-BDE congeners)
      come from exogenous exposure for female and male hair, respectively. The higher
      contribution of exogenous exposure for less-brominated congeners could be related
      to their relatively lower log KOW and higher volatility than higher-brominated
      congeners, which make them more readily to evaporate from dust and then to be
      adsorbed on hair. Higher hair PBDE levels and higher exogenous exposure of less
      brominated congeners in females than in males can be attributed to a longer
      exogenous exposure time for females than males. Significant positive
      relationships were found in tri- to hepta-BDE congeners (BDE 28, 47, 66, 85, 100,
      153, 154, and 183) (R = 0.36-0.55, p < 0.05) between hair and serum, but this
      relationship was not found for octa- to deca-BDE. Difference in the half-lives
      between highly brominated congeners and less-brominated congeners could be a
      reason. This result also implied that we should treat the results of correlation
      analyses between hair and other organs cautiously. 

PMID- 24320082
TI  - Efficient role of BacTN635 on the safety properties, sensory attributes, and
      texture profile of raw minced meat beef and chicken breast.
AB  - Bacteriocin BacTN635, produced by Lactobacillus plantarum sp. TN635, was purified
      and characterised in previous work. In this study we report the biotechnological
      application of this bacteriocin as a biopreservative during storage at 4 degrees
      C of raw minced meat beef and chicken breast. Overall, the results obtained
      showed that the addition of the semi-purified BacTN635 at 500 or 1000 AU g(-1) in
      raw minced meat beef and chicken breast can delay the proliferation of spoilage
      microorganisms, suppress the growth of the pathogenic microorganism Listeria
      monocytogenes, improve sensory quality, texture attributes, and extend the shelf
      life of these two meat products during refrigerated storage. BacTN635 at 1000 AU
      g(-1) could extend the shelf-life, and the meat showed good sensory
      characteristics. Therefore, treatment with semi-purified BacTN635 can be used as
      a safe method for preservation of raw minced meat beef and chicken breast.

PMID- 24320083
TI  - Methyl coenzyme M reductase (mcrA) gene abundance correlates with activity
      measurements of methanogenic H2 /CO2 -enriched anaerobic biomass.
AB  - Biologically produced methane (CH4) from anaerobic digesters is a renewable
      alternative to fossil fuels, but digester failure can be a serious problem.
      Monitoring the microbial community within the digester could provide valuable
      information about process stability because this technology is dependent upon the
      metabolic processes of microorganisms. A healthy methanogenic community is
      critical for digester function and CH4 production. Methanogens can be surveyed
      and monitored using genes and transcripts of mcrA, which encodes the alpha
      subunit of methyl coenzyme M reductase - the enzyme that catalyses the final step
      in methanogenesis. Using clone libraries and quantitative polymerase chain
      reaction, we compared the diversity and abundance of mcrA genes and transcripts
      in four different methanogenic hydrogen/CO2 enrichment cultures to function, as
      measured by specific methanogenic activity (SMA) assays using H2 /CO2 . The mcrA
      gene copy number significantly correlated with CH4 production rates using H2 /CO2
      , while correlations between mcrA transcript number and SMA were not significant.
      The DNA and cDNA clone libraries from all enrichments were distinctive but
      community diversity also did not correlate with SMA. Although hydrogenotrophic
      methanogens dominated these enrichments, the results indicate that this
      methodology should be applicable to monitoring other methanogenic communities in
      anaerobic digesters. Ultimately, this could lead to the engineering of digester
      microbial communities to produce more CH4 for use as renewable fuel.

PMID- 24320085
TI  - Serum paraoxonase 1 status and its association with atherogenic indexes in
      gentamicin-induced nephrotoxicity in rats treated with coenzyme Q10.
AB  - Coenzyme Q10 is a natural antioxidant and scavenger of free radicals. In the
      present study, we examined the effect of coenzyme Q10 on paraoxonase 1 (PON1)
      activity, lipid profile, atherogenic indexes and relationship of PON 1 activity
      by high-density lipoprotein (HDL) and atherogenic indexes in gentamicin (GM)
      induced nephrotoxicity rats. Thirty Sprague-Dawley rats were divided into three
      groups to receive saline; GM, 100 mg/kg/d; and GM plus coenzyme Q10 by 15 mg/kg
      i.p daily, respectively. After 12 days, animals were anaesthetized, blood samples
      were also collected before killing to measure the levels of triglyceride (TG),
      cholesterol (C), low-density lipoprotein (LDL), very low density lipoprotein
      (VLDL), HDL, atherogenic indexes and the activities of PON1 of all groups were
      analyzed. Data were analyzed by non-parametric Mann-Whitney test (using SPSS 13
      software). Coenzyme Q10 significantly decreased TG, C, LDL, VLDL, atherogenic
      index, atherogenic coefficient and cardiac risk ratio. HDL level and PON1
      activity were significantly increased when treated with coenzyme Q10. Also, the
      activity of PON 1 correlated positively with HDL and negatively with atherogenic
      coefficient, cardiac risk ratio 1 and cardiac risk ratio 2. This study showed
      that coenzyme Q10 exerts beneficial effects on PON1 activity, lipid profile,
      atherogenic index and correlation of PON 1 activity with HDL and atherogenic
      index in GM -induced nephrotoxicity rats.

PMID- 24320086
TI  - Resveratrol suppresses inflammatory responses in endometrial stromal cells
      derived from endometriosis: a possible role of the sirtuin 1 pathway.
AB  - AIM: Endometriosis is a chronic inflammatory disease. Sirtuin 1 (SIRT1) plays a
      role in regulation of inflammation. The role of SIRT1 in endometriosis remains
      unknown. We here addressed the anti-inflammatory effects of SIRT1 on
      endometriosis. METHODS: The expression of SIRT1 in human ovarian endometriomas
      and eutopic endometria were examined using immunohistochemistry and reverse
      transcription polymerase chain reaction (RT-PCR). Endometriotic stromal cells
      (ESC) obtained from endometriomas were exposed to either resveratrol or sirtinol,
      an activator or inhibitor of sirtuins, respectively, and tumor necrosis factor
      (TNF)-alpha-induced interleukin (IL)-8 release from the ESC was assessed at mRNA
      and protein levels. RESULTS: Both immunochemistry and RT-PCR demonstrated that
      SIRT1 was expressed in ESC and normal endometrial stromal cells. Resveratrol
      suppressed TNF-alpha-induced IL-8 release from the ESC in a dose-dependent manner
      while sirtinol increased IL-8 release. CONCLUSION: These opposing effects of
      SIRT1-related agents suggest that IL-8 release from the ESC is modulated through
      the SIRT1 pathway. Resveratrol may have the potential to ameliorate local
      inflammation in endometriomas.

PMID- 24320087
TI  - Control of outflow resistance by soluble adenylyl cyclase.
AB  - Abstract Glaucoma is a leading cause of blindness in the United States affecting
      as many as 2.2 million Americans. All current glaucoma treatment strategies aim
      to reduce intraocular pressure, even in patients with normal tension glaucoma.
      Typically, this is accomplished by reducing the rate of aqueous flow by limiting
      aqueous production or enhancing drainage using drugs and surgery. Whereas these
      strategies are effective in diminishing vision loss, some patients continue to
      lose vision and many discontinue use of their medications because of undesirable
      side effects. Drugs known to be effective in altering conventional outflow have
      for the most part been abandoned from modern clinical practice due to undesirable
      side effects. Identification of new drugs that could enhance conventional
      outflow, would offer additional options in the treatment of glaucoma and ocular
      hypertension. To this end, our laboratory has recently uncovered a novel pathway
      for regulation of conventional outflow by the ciliary body. This pathway is
      dependent on soluble adenylyl cyclase, an enzyme that catalyzes the generation of
      cyclic adenosine 3',5' monophosphate (cAMP) in response to bicarbonate. 

PMID- 24320088
TI  - A comparison of trabecular meshwork sphingolipids and ceramides of ocular
      normotensive and hypertensive states of DBA/2J mice.
AB  - PURPOSE: To determine the differential profiles of sphingomyelin, sphingoid base,
      sphingoid base-1-phosphate, and ceramide and their quantitative differences
      between trabecular meshwork (TM) derived from normotensive and hypertensive
      intraocular pressure states of DBA/2J mice. METHODS: Normotensive and
      hypertensive state TM were collected from mice and analyzed. Lipid extraction was
      performed using the Bligh and Dyer method, and the protein concentrations were
      determined using the Bradford method. The lipids were identified and quantified
      using appropriate standards with a TSQ Quantum Access Max triple quadrupole mass
      spectrometer applying class-specific lipid identification settings. RESULTS: The
      comparative profiles of sphingomyelin, sphingoid base, sphingoid base-1
      phosphate, and ceramide between normotensive and hypertensive TM showed several
      species unique to a phase and as well common between states. CONCLUSION: The
      presence or absence of several sphingolipids and ceramides in the normotensive or
      hypertensive states may contribute to better understanding of the glaucomas.

PMID- 24320089
TI  - Critical appraisal of evidence supporting the placement of dental implants in
      patients with neurodegenerative diseases.
AB  - OBJECTIVE: To assess the available scientific evidence regarding the
      effectiveness and complications associated with using dental implants in patients
      with neurodegenerative diseases. MATERIALS AND METHODS: PubMed, EMBASE, Biosis
      Citation Index, CINAHL, Web of Science and LILACS electronic databases were
      searched, with the last search performed on 20 May 2013. Reference lists of the
      included systematic reviews were manually reviewed. No restriction regarding the
      study design or publication language was applied for study inclusion. Only
      studies involving human subjects were included. In case randomised or other
      controlled trials were identified, methodological assessment of included studies
      was planned. RESULTS: Fifty-eight potential papers were initially retrieved from
      the electronic databases. Eleven papers were finally included. No randomised
      controlled trial or other controlled trial was found. Eight papers were case
      reports and three were case series. The sample included three types of
      neurodegenerative diseases: dementia, Parkinson's disease and Huntington's
      disease. Generally, the reports showed improvements in chewing function and
      quality of life after the placement of implants and prostheses. Nevertheless, the
      follow-up time was typically short (<=12 months), and the overall sample size was
      small (N = 22 patients). Inclusion of studies without controls prevented a more
      robust methodological assessment from being performed. CONCLUSIONS: The results
      of the included reports suggest positive outcomes for dental implant use in
      patients with neurodegenerative diseases. Nevertheless, more robust studies, with
      better design and longer follow-ups, are needed to set strategies to prevent and
      treat potential complications in patients with neurodegenerative disorders
      treated with dental implants.

PMID- 24320090
TI  - Tongue-tie-the disease du jour.

PMID- 24320092
TI  - Inducible offences affect predator-prey interactions and life-history plasticity
      in both predators and prey.
AB  - Phenotypic plasticity can have strong impacts on predator-prey interactions.
      Although much work has examined the effects of inducible defences, less
      understood is how inducible offences in predators affect predator-prey
      interactions and predator and prey phenotypes. Here, we examine the impacts of an
      inducible offence on the interactions and life histories of a cohort of predatory
      Hynobius retardatus salamander larvae and their prey, Rana pirica tadpoles. We
      examined larval (duration, survival) and post-metamorphic (size) traits of both
      species after manipulating the presence/absence of tadpoles and salamanders with
      offensive (broadened gape width) or non-offensive phenotypes in pond enclosures.
      Offensive phenotype salamanders reduced tadpole survival and metamorph emergence
      by 58% compared to tadpole-only treatments, and by over 30% compared to non
      offensive phenotypes. Average time to metamorphosis of frogs was delayed by 30%
      in the presence of salamanders, although this was independent of salamander
      phenotype. Thus, offensive phenotype salamanders reduced the number of tadpoles
      remaining in the pond over time by reducing tadpole survival, not by altering
      patterns of metamorph emergence. Offensive phenotypes also caused tadpoles to
      metamorphose 19% larger than no salamander treatments and 6% larger than non
      offensive phenotype treatments. Pooled across salamander treatments, tadpoles
      caused salamanders to reach metamorphosis faster and larger. Moreover, in the
      presence of tadpoles, offensive phenotype salamanders metamorphosed 25% faster
      and 5% larger than non-offensive phenotype salamanders, but in their absence,
      neither their size nor larval period differed from non-offensive phenotype
      individuals. To our knowledge, this study is the first to demonstrate that
      inducible offences in predators can have strong impacts on predator and prey
      phenotypes across multiple life stages. Since early metamorphosis at a larger
      size has potential fitness advantages, the impacts of offensive phenotypes on
      frog and salamander life histories likely have significant consequences for
      individuals and populations. Furthermore, increased predation on tadpoles likely
      causes offensive phenotype individuals to have strong impacts on pond
      communities. Future studies should examine the fitness consequences of
      morphological and life-history plasticity across multiple life stages and should
      address the population and community level consequences of offensive phenotypes. 

PMID- 24320091
TI  - ABM Clinical Protocol #5: Peripartum breastfeeding management for the healthy
      mother and infant at term, revision 2013.
AB  - A central goal of The Academy of Breastfeeding Medicine is the development of
      clinical protocols for managing common medical problems that may impact
      breastfeeding success. These protocols serve only as guidelines for the care of
      breastfeeding mothers and infants and do not delineate an exclusive course of
      treatment or serve as standards of medical care. Variations in treatment may be
      appropriate according to the needs of an individual patient.

PMID- 24320093
TI  - Syntheses of fused tetracyclic quinolines via Ugi-variant MCR and Pd-catalyzed
      bis-annulation.
AB  - Diversity-oriented synthesis of fused tetracyclic 6,11-dihydroquinoxalino[2,3
      b]quinolines is described via a sequential Ugi-variant multicomponent reaction
      and Pd-catalyzed bis-annulation in one-pot process. 

PMID- 24320094
TI  - Mothers' cognitive references to 2-year-olds predict theory of mind at ages 6 and
      10.
AB  - Mothers' mental-state references predict individual differences in preschoolers'
      false-belief (FB) understanding; less is known about the origins of corresponding
      variation in school-age children. To address this gap, 105 children completed
      observations with their mothers at child ages 2 and 6, three FB tasks and a
      verbal comprehension test at age 3, and five FB tasks at age 6. Seventy-seven of
      these children completed five Strange Stories at age 10. Individual differences
      in mothers' cognitive references at child age 2 predicted variation in children's
      FB understanding at age 6 and Strange Stories scores at age 10 (controlling for
      number of mothers' turns and children's mental-state references, verbal
      comprehension and FB understanding at age 3, and mothers' cognitive references at
      child age 6). 

PMID- 24320095
TI  - Understanding and meeting the needs of women in the postpartum period: the
      Perinatal Maternal Health Promotion Model.
AB  - A new model for the care of women in the postpartum focuses on the development of
      life skills that promote complete well-being. The year following childbirth is a
      time of significant transition for women. In addition to the physiologic changes
      associated with the postpartum period, a woman undergoes marked psychosocial
      changes as she transitions into a motherhood role, reestablishes relationships,
      and works to meet the physical and emotional needs of her infant and other family
      members. It is a time when women are vulnerable to health problems directly
      related to childbirth and to compromised self-care, which can manifest in the
      development or reestablishment of unhealthy behaviors such as smoking and a
      sedentary lifestyle. In addition to long-term implications for women, compromised
      maternal health in the postpartum period is associated with suboptimal health and
      developmental outcomes for infants. Maternal health experts have called for a
      change in how care is provided for women in the postpartum period. This article
      presents the rationale for a health promotion approach to meeting the needs of
      women in the postpartum period and introduces the Perinatal Maternal Health
      Promotion Model. This conceptual framework is built around a definition of
      maternal well-being that asserts that health goes beyond merely the absence of
      medical complications. In the model, the core elements of a healthy postpartum
      are identified and include not only physical recovery but also the ability to
      meet individual needs and successfully transition into motherhood. These goals
      can best be achieved by helping women develop or strengthen 4 key individual
      health-promoting skills: the ability to mobilize social support, self-efficacy,
      positive coping strategies, and realistic expectations. While the model focuses
      on the woman, the health promotion approach takes into account that maternal
      health in this critical period affects and is affected by her family, social
      network, and community. Clinical implications of the model are addressed,
      including specific health promotion strategies that clinicians can readily
      incorporate into antepartum and postpartum care. 

PMID- 24320096
TI  - Distribution and chemical speciation of arsenic in ancient human hair using
      synchrotron radiation.
AB  - Pre-Columbian populations that inhabited the Tarapaca mid river valley in the
      Atacama Desert in Chile during the Middle Horizon and Late Intermediate Period
      (AD 500-1450) show patterns of chronic poisoning due to exposure to geogenic
      arsenic. Exposure of these people to arsenic was assessed using synchrotron-based
      elemental X-ray fluorescence mapping, X-ray absorption spectroscopy, X-ray
      diffraction and Fourier transform infrared spectromicroscopy measurements on
      ancient human hair. These combined techniques of high sensitivity and specificity
      enabled the discrimination between endogenous and exogenous processes that has
      been an analytical challenge for archeological studies and criminal
      investigations in which hair is used as a proxy of premortem metabolism. The high
      concentration of arsenic mainly in the form of inorganic As(III) and As(V)
      detected in the hair suggests chronic arsenicism through ingestion of As-polluted
      water rather than external contamination by the deposition of heavy metals due to
      metallophilic soil microbes or diffusion of arsenic from the soil. A decrease in
      arsenic concentration from the proximal to the distal end of the hair shaft
      analyzed may indicate a change in the diet due to mobility, though chemical or
      microbiologically induced processes during burial cannot be entirely ruled out. 

PMID- 24320097
TI  - The effect of nutrition intervention in lung cancer patients undergoing
      chemotherapy and/or radiotherapy: a systematic review.
AB  - The prevalence of malnutrition in lung cancer patients across a variety of
      treatment modalities and disease stages ranges from 45% to 69%. Malnutrition is
      associated with poorer clinical outcomes in cancer patients. This systematic
      review examined whether dietary counseling or oral supplements during
      chemotherapy and/or radiotherapy in patients with lung cancer affect patient or
      clinical outcomes. Relevant nutrition intervention studies from 1980 to March
      2012 were identified. Articles meeting predetermined inclusion/exclusion criteria
      were critically appraised and included in the review. The outcomes of interest
      included dietary intake, weight, nutritional status, quality of life, functional
      status, treatment response, and survival. Five eligible studies were identified
      including 3 randomized controlled trials, 1 historical cohort, and 1 case series.
      These studies suggest dietary counseling improves energy and protein intake
      during chemotherapy in patients with lung cancer but has no benefit to other
      outcomes during chemotherapy. There is insufficient evidence regarding the effect
      on patient or clinical outcomes during radiotherapy. Randomized trials examining
      dietary counseling in patients with lung cancer during radiotherapy are required.

PMID- 24320098
TI  - One-pot regiospecific synthesis of imidazo[1,2-a]pyridines: a novel, metal-free,
      three-component reaction for the formation of C-N, C-O, and C-S bonds.
AB  - A novel transition-metal-free three-component reaction for the construction of
      imidazo[1,2-a]pyridines has been developed. It represents a facile approach for
      the formation of C-N, C-O, and C-S bonds from ynals, pyridin-2-amines, and
      alcohols or thiols. 

PMID- 24320099
TI  - Seropositivity of HPV 16 E6 and E7 and the risk of oral cancer.
AB  - OBJECTIVES: The objective of the study was to determine the prevalence of HPV
      seropositivity among patients with oral squamous cell carcinoma (OSCC) and
      healthy individuals and to correlate the association between HPV 16
      seropositivity and risk of OSCC. MATERIALS AND METHODS: HPV 16 E6 and E7 plasmids
      were constructed for the production of recombinant protein, which was used as the
      antigen in ELISA. HPV ELISA was performed on serum samples from 50 healthy
      individuals and 50 patients with OSCC. RESULTS: Using the HPV ELISA, 30% (OR =
      2.25, 95% CI = 0.85-5.93) and 18% (OR = 1.61, 95% CI = 0.53-4.92) of patients
      with oral cancer were found to be HPV 16 E6 and E7 seropositive, respectively.
      Significant association was found between HPV 16 seropositivity and increased
      risk of OSCC in men, but not in male subjects. A similar trend was observed in
      non-betel quid chewers. CONCLUSIONS: Potential associations between HPV 16 E6/E7
      seropositivity and oral cancer were revealed in men and non-betel quid chewer
      subjects, suggesting a possible etiological role of HPV 16 in subgroup of
      patients with OSCC in Malaysia.

PMID- 24320100
TI  - Systemic sarcoidosis with specific cutaneous lesions located at insulin injection
      sites for diabetes mellitus.

PMID- 24320101
TI  - The future is here: a review of foresight systems in anxiety and depression.
AB  - Cognitive models of anxiety and depression have long suggested a central role for
      future-oriented thinking in these disorders. Experimental studies suggest that
      anxiety and depression are characterised by distinct future-oriented thinking
      profiles, and that these profiles are markedly different from those of
      asymptomatic adults. In this paper, we review these profiles and propose two
      explanatory models marked by two different neurocognitive systems. The
      Reconstructive Memory Model emphasises a role for emotionally driven learning and
      retrieval in episodic foresight (i.e., the construction of future-oriented
      scenarios), and the Valuation Model proposes that an overweighing of risk and
      uncertainty estimates can be invoked to explain the future-oriented thought
      patterns. We consider the effectiveness of interventions aimed at altering such
      thought patterns. We suggest that future research aimed at elucidating the
      neurobiological underpinnings of future-oriented thinking in anxiety and
      depression can play an important role in advancing development of effective
      biological and psychosocial interventions for these disorders. 

PMID- 24320102
TI  - Long-term oncological and reproductive outcomes of fertility-sparing
      cytoreductive surgery in females aged 25 years and younger with malignant ovarian
      germ cell tumors.
AB  - AIM: To evaluate the long-term oncological and reproductive outcomes of patients
      aged 25 years and younger who were treated by fertility-sparing cytoreductive
      surgery (FSCS) plus adjuvant chemotherapy (ACT) or observation alone for
      malignant ovarian germ cell tumors (MOGCT). METHODS: Records of 42 eligible
      female patients treated for MOGCT between 1 May 1995 and 31 December 2010 at two
      centers were analyzed retrospectively. A telephone questionnaire was performed to
      gather reproductive and menstrual history. RESULTS: One patient was treated
      without FSCS and two patients were lost to follow-up. The mean age of the
      remaining 39 patients was 18.4 +/- 3.2 years. Eighteen of the tumors were
      histologically pure dysgerminomas (PD) and 21 were non-dysgerminomatous tumors
      (non-DT). Thirteen patients (33%) presented with stage II-III disease. Optimal
      cytoreduction was achieved in 34 of the 39 patients (87%). Systematic pelvic and
      para-aortic lymphadenectomy was performed in 31 of the 39 patients (79.5%). The
      frequency of lymph node metastasis was 29% (9/31). Twenty-seven patients (69.2%)
      received ACT. Disease recurred in six (15.3%) patients, all in the non-DT group.
      Four of six underwent secondary optimal FSCS followed by chemotherapy.
      Retroperitoneal nodal recurrence was detected in two of these four patients
      (50%). Four deaths occurred, three due to chemoresistant aggressive disease and
      one due to secondary acute myelocytic leukemia. The overall survival rates for
      patients with PD and non-DT were 100% and 81.4%, respectively. Twenty-three of 27
      patients who received ACT continued their regular menses. Sixteen spontaneous
      pregnancies and one pregnancy by intrauterine insemination were achieved by 21
      patients who attempted conception. CONCLUSION: Either primary or secondary FSCS
      followed by ACT seems to be a feasible and safe approach to preserving future
      fertility and hormonal function in young patients with MOGCT.

PMID- 24320103
TI  - Hemipelvectomy: modified surgical technique and clinical experiences from a
      retrospective study.
AB  - OBJECTIVE: To report a technique for hemipelvectomy surgery in the dog and cat.
      STUDY DESIGN: Descriptive report. ANIMALS: Dogs and cats. METHODS: To describe
      patient selection and an anatomically based surgical technique for
      hemipelvectomy. RESULTS: Surgery of the pelvis requires detailed anatomic
      knowledge of the pelvic region. Hemipelvectomy is a major surgical procedure with
      potential for substantial hemorrhage because of transection through large muscle
      groups and proximity to major vessels. The anatomic dissection may enable better
      adherence to principles of compartmental resection of tumors and reduced patient
      morbidity. CONCLUSIONS: When performed with appropriate care, preoperative
      planning, and good anesthesia support, hemipelvectomy can be performed safely and
      is effective for radical excision of various tumor types arising from or near the
      pelvis.

PMID- 24320104
TI  - Targeted thermosensitive liposomes: an attractive novel approach for increased
      drug delivery to solid tumors.
AB  - INTRODUCTION: Currently available chemotherapy is hampered by a lack in tumor
      specificity and resulting toxicity. Small and long-circulating liposomes can
      preferentially deliver chemotherapeutic drugs to tumors upon extravasation from
      tumor vasculature. Although clinically used liposomal formulations demonstrated
      significant reduction in toxicity, enhancement of therapeutic activity has not
      fully met expectations. AREAS COVERED: Low drug bioavailability from liposomal
      formulations and limited tumor accumulation remain major challenges to further
      improve therapeutic activity of liposomal chemotherapy. The aim of this review is
      to highlight strategies addressing these challenges. A first strategy uses
      hyperthermia and thermosensitive liposomes to improve tumor accumulation and
      trigger liposomal drug bioavailability. Image-guidance can aid online monitoring
      of heat and drug delivery and further personalize the treatment. A second
      strategy involves tumor-specific targeting to enhance drug delivery specificity
      and drug internalization. In addition, we review the potential of combinations of
      the two in one targeted thermosensitive-triggered drug delivery system. EXPERT
      OPINION: Heat-triggered drug delivery using thermosensitive liposomes as well as
      the use of tumor vasculature or tumor cell-targeted liposomes are both promising
      strategies to improve liposomal chemotherapy. Preclinical evidence has been
      encouraging and both strategies are currently undergoing clinical evaluation. A
      combination of both strategies rendering targeted thermosensitive liposomes
      (TTSL) may appear as a new and attractive approach promoting tumor drug delivery.

PMID- 24320105
TI  - The effect of topical virgin coconut oil on SCORAD index, transepidermal water
      loss, and skin capacitance in mild to moderate pediatric atopic dermatitis: a
      randomized, double-blind, clinical trial.
AB  - Atopic dermatitis (AD) is a chronic skin disease characterized by defects in the
      epidermal barrier function and cutaneous inflammation, in which transepidermal
      water loss (TEWL) is increased and the ability of the stratum corneum to hold
      water is impaired, causing decreased skin capacitance and hydration. This study
      investigated the effects of topical virgin coconut oil (VCO) and mineral oil,
      respectively, on SCORAD (SCORing of Atopic Dermatitis) index values, TEWL, and
      skin capacitance in pediatric patients with mild to moderate AD, using a
      randomized controlled trial design in which participants and investigators were
      blinded to the treatments allocated. Patients were evaluated at baseline, and at
      2, 4, and 8 weeks. A total of 117 patients were included in the analysis. Mean
      SCORAD indices decreased from baseline by 68.23% in the VCO group and by 38.13%
      in the mineral oil group (P < 0.001). In the VCO group, 47% (28/59) of patients
      achieved moderate improvement and 46% (27/59) showed an excellent response. In
      the mineral oil group, 34% (20/58) of patients showed moderate improvement and
      19% (11/58) achieved excellent improvement. The VCO group achieved a post
      treatment mean TEWL of 7.09 from a baseline mean of 26.68, whereas the mineral
      oil group demonstrated baseline and post-treatment TEWL values of 24.12 and
      13.55, respectively. In the VCO group, post-treatment skin capacitance rose to
      42.3 from a baseline mean of 32.0, whereas that in the mineral oil group
      increased to 37.49 from a baseline mean of 31.31. Thus, among pediatric patients
      with mild to moderate AD, topical application of VCO for eight weeks was superior
      to that of mineral oil based on clinical (SCORAD) and instrumental (TEWL, skin
      capacitance) assessments.

PMID- 24320106
TI  - Accumulation kinetics and equilibrium partitioning coefficients for semivolatile
      organic pollutants in forest litter.
AB  - Soils are important stores of environmentally cycling semivolatile organic
      contaminants (SVOCs) and represent relevant atmospheric secondary sources
      whenever environmental conditions favor re-emission. The exchange between air and
      soil is controlled by resistances posed by interfacial matrices such as the
      ubiquitously distributed vegetation litter. For the first time, this study
      focused on the experimental characterization of accumulation parameters for SVOCs
      in litter under real field conditions. The logarithm of the litter-air
      equilibrium partitioning coefficient ranged 6.8-8.9 and had a similar dependence
      on logKOA as that of plant foliage and soil data. Uptake and release rates were
      also KOA dependent with values (relevant for real environmental conditions)
      ranging 30,000-150,000 d(-1) and 0.0004-0.0134 d(-1), respectively. The overall
      mass transfer coefficient v controlling litter-air exchange (0.03-1.4 cm s(-1))
      was consistent with previously reported data of v for foliage in forest canopies
      after normalization on leaf area index. Obtained data suggest that litter holds
      the potential for influencing atmospheric fugacity in proximity to soil, likely
      affecting overall exchange of SVOCs between the soil reservoir and the
      atmosphere. 

PMID- 24320107
TI  - Guitar-string sutures to reduce a large surgical defect prior to skin grafting or
      flap movement.

PMID- 24320108
TI  - Preparation and performance of hydroxypropyl methylcellulose esters of
      substituted succinates for in vitro supersaturation of a crystalline hydrophobic
      drug.
AB  - We prepared hydroxypropyl methylcellulose (HPMC) esters of substituted succinates
      and examined their performance for improving the aqueous solubility of
      crystalline hydrophobic drugs in spray-dried dispersions (SDDs). From one HPMC,
      we synthesized five HPMC esters using various monosubstituted succinic
      anhydrides. These HPMC esters along with a commercial HPMC acetate succinate
      (HPMCAS) were spray-dried from solutions with phenytoin. The SDDs with different
      matrices at 10 wt % loading had very similar bulk properties with a minimal
      amount of detectable crystalline phenytoin as revealed by scanning electron
      microscopy (SEM), powder X-ray diffraction (powder XRD), and differential
      scanning calorimetry (DSC). In solution, while the SDD with HPMCAS was very
      effective at achieving high levels of phenytoin supersaturation initially, it was
      not competent at maintaining such supersaturation due to the rapid
      crystallization of the dissolved phenytoin. Alternatively, SDDs with several
      synthesized HPMC esters of substituted succinates not only achieved rather high
      initial supersaturation but also maintained high concentrations for extended time
      (i.e., 1.5 h and longer). Such maintenance was largely ascribed to the inhibition
      of phenytoin nucleation. Structure-property relationships were established, and
      the most successful systems contained a high degree of substitution and a
      combination of a thioether with neighboring weak electron-withdrawing groups in
      the substituted succinic anhydrides. The effective maintenance of supersaturated
      solutions was only found in SDDs with rather low drug loadings, which indicates
      the significance of sufficiently high concentrations of polymer additives in the
      dissolution media. 

PMID- 24320109
TI  - Tonotopic reorganization and spontaneous firing in inferior colliculus during
      both short and long recovery periods after noise overexposure.
AB  - BACKGROUND: Noise induced injury of the cochlea causes shifts in activation
      thresholds and changes of frequency response in the inferior colliculus (IC).
      Noise overexposure also induces pathological changes in the cochlea, and is
      highly correlated to hearing loss. However, the underlying mechanism has not been
      fully elucidated. In this study, we hypothesized that overexposure to noise
      induces substantial electrophysiological changes in the IC of guinea pigs.
      RESULTS: During the noise exposure experiment, the animals were undergoing a
      bilateral exposure to noise. Additionally, various techniques were employed
      including confocal microscopy for the detection of cochlea hair cells and single
      neuron recording for spontaneous firing activity measurement. There were
      alterations among three types of frequency response area (FRA) from sound
      pressure levels, including V-, M-, and N-types. Our results indicate that
      overexposure to noise generates different patterns in the FRAs. Following a short
      recovery (one day after the noise treatment), the percentage of V-type FRAs
      considerably decreased, whereas the percentage of M-types increased. This was
      often caused by a notch in the frequency response that occurred at 4 kHz (noise
      frequency). Following a long recovery from noise exposure (11-21 days), the
      percentage of V-types resumed to a normal level, but the portion of M-types
      remained high. Interestingly, the spontaneous firing in the IC was enhanced in
      both short and long recovery groups. CONCLUSION: Our data suggest that noise
      overexposure changes the pattern of the FRAs and stimulates spontaneous firing in
      the IC in a unique way, which may likely relate to the mechanism of tinnitus.

PMID- 24320110
TI  - Do neutrophil gelatinase-associated lipocalin and interleukin-18 predict renal
      dysfunction in patients with familial Mediterranean fever and amyloidosis?
AB  - BACKGROUND: The aim of this study was to evaluate whether neutrophil gelatinase
      associated lipocalin (NGAL) and interleukin-18 (IL-18) predict renal disfunction
      in patients with familial Mediterranean fever (FMF). METHODS: This prospective
      study consisted of 102 patients with FMF in attack-free period, and 40 matched
      healthy controls. Of the patients, nine were diagnosed as amyloidosis. The
      patients were divided into two groups according to eGFR as below 120 mL per
      minute and above 120 mL per minute. Also, patients were divided into three groups
      according to the degree of urinary albumin excretion as normoalbuminuric,
      microalbuminuric, and macroalbuminuric. The serum levels of IL-18 (sIL-18) and
      NGAL (sNGAL), and urinary levels of IL-18 (uIL-18) and NGAL (uNGAL) were measured
      by using ELISA kits. RESULTS: The levels of sIL-18, sNGAL, uIL-18, and uNGAL were
      detected significantly higher in FMF patients, particularly in patients with
      amyloidosis, when compared to controls. sNGAL, uIL-18, and uNGAL were
      significantly higher in patients with eGFR < 120 mL per minute than in patients
      with eGFR >= 120 mL per minute. sNGAL, uIL-18, and uNGAL were correlated
      significantly with urinary albumin excretion, additionally, were inverse
      correlated with eGFR. The most remarkable findings of this study are of the
      higher values of sIL-18, sNGAL, uIL-18, and uNGAL in both normoalbuminuric FMF
      patients and patients with eGFR >= 120 mL per minute. CONCLUSIONS: The results of
      this study suggest that sIL-18, uIL-18, sNGAL, and uNGAL are reliable markers of
      early renal disfunction in FMF patients, and may let us take measures from the
      early stage of renal involvement.

PMID- 24320112
TI  - Predicting individual variation in language from infant speech perception
      measures.
AB  - There are increasing reports that individual variation in behavioral and
      neurophysiological measures of infant speech processing predicts later language
      outcomes, and specifically concurrent or subsequent vocabulary size. If such
      findings are held up under scrutiny, they could both illuminate theoretical
      models of language development and contribute to the prediction of communicative
      disorders. A qualitative, systematic review of this emergent literature
      illustrated the variety of approaches that have been used and highlighted some
      conceptual problems regarding the measurements. A quantitative analysis of the
      same data established that the bivariate relation was significant, with
      correlations of similar strength to those found for well-established
      nonlinguistic predictors of language. Further exploration of infant speech
      perception predictors, particularly from a methodological perspective, is
      recommended. 

PMID- 24320113
TI  - Early sequence of events triggered by the interaction of Neisseria meningitidis
      with endothelial cells.
AB  - Neisseria meningitidis is a bacterium responsible for severe sepsis and
      meningitis. Following type IV pilus-mediated adhesion to endothelial cells,
      bacteria proliferating on the cellular surface trigger a potent cellular response
      that enhances the ability of adhering bacteria to resist the mechanical forces
      generated by the blood flow. This response is characterized by the formation of
      numerous 100 nm wide membrane protrusions morphologically related to filopodia.
      Here, a high-resolution quantitative live-cell fluorescence microscopy procedure
      was designed and used to study this process. A farnesylated plasma membrane
      marker was first detected only a few seconds after bacterial contact, rapidly
      followed by actin cytoskeleton reorganization and bulk cytoplasm accumulation.
      The bacterial type IV pili-associated minor pilin PilV is necessary for the
      initiation of this cascade. Plasma membrane composition is a key factor as
      cholesterol depletion with methyl-beta-cyclodextrin completely blocks the
      initiation of the cellular response. In contrast membrane deformation does not
      require the actin cytoskeleton. Strikingly, plasma membrane remodelling
      undermicrocolonies is also independent of common intracellular signalling
      pathways as cellular ATP depletion is not inhibitory. This study shows that
      bacteria-induced plasma membrane reorganization is a rapid event driven by a
      direct cross-talk between type IV pili and the plasma membrane rather than by the
      activation of an intracellular signalling pathway that would lead to actin
      remodelling. 

PMID- 24320114
TI  - Pd-catalyzed oxidative coupling of arene C-H bonds with benzylic ethers as acyl
      equivalents.
AB  - A palladium-catalyzed oxidative coupling of arene C-H bonds with benzylic ethers
      via C-H bond activation is described. The reaction proceeds efficiently with a
      broad range of substrates bearing conventional directing groups with excellent
      functional group compatibility. This protocol potentially provides opportunities
      to use dibenzyl ethers as new acyl equivalents for catalytic acylation reactions.

PMID- 24320115
TI  - Abstracts of the 58th Annual Meeting of the Scientific and Standardization
      Committee of the International Society on Thrombosis and Haemostasis. June 27-30,
      2012.

PMID- 24320116
TI  - Glycans in regeneration.
AB  - Glycans participate in many key cellular processes during development and in
      physiology and disease. In this review, the functional role of various glycans in
      the regeneration of neurons and body parts in adult metazoans is discussed.
      Understanding glycosylation may facilitate research in the field of stem cell
      biology and regenerative medicine. 

PMID- 24320117
TI  - Important interactional strategies for everyday public health nursing practice.
AB  - This Clinical Concepts article concerns the relational tools required by public
      health nurses to establish relationships with single mothers living on public
      assistance, mothers who are vulnerable and often stigmatized. The implications of
      stigmatization for relationship building are highlighted based on previous
      research investigating how public health nurses working in Canadian jurisdictions
      establish professional caring relationships with this cohort of mothers. Public
      health nurses employed interactional strategies including engaging in a positive
      manner and offering verbal commendations which served as effective relational
      tools to break through mothers' walls of defensiveness and to resume the dynamic
      process of relationship building. Building Relationship is a key practice
      standard for public health nurses and is instrumental to their work at both
      individual and community levels to improve social determinants of health. The
      author concludes with recommendations to facilitate building relationships during
      everyday public health nursing practice. 

PMID- 24320118
TI  - True ectopic ovary in the right iliac fossa mimicking acute appendicitis and
      associated with ipsilateral renal agenesis.
AB  - Ectopic ovarian tissue is a rare gynecologic condition. The presence of ectopic
      ovary may be accompanied by maldevelopments of the genital and urinary tract. We
      report an extremely rare case of a 39-year-old woman presenting with abdominal
      pain localized in the right lower quadrant. During the preoperative investigation
      and the exploratory laparotomy, an ectopic ovary in contact with the appendix
      accompanied by a single left kidney was found. The present report also includes a
      review of the related published work. To the best of our knowledge, this is one
      of the very few cases reported describing the co-occurrence of true ovarian
      ectopia and ipsilateral renal agenesis. 

PMID- 24320120
TI  - Hidden patients: the relatives of patients in need of palliative care.
AB  - BACKGROUND: When identifying patients for palliative care, medical specialists
      find it necessary to disclose "hidden" patients: the patient's relatives. The
      issue has been discussed sporadically in Bulgaria; the present study was part of
      a larger investigation that examined the opinion of medical specialists,
      patients, and their relatives. METHOD: The study protocol was explained to
      participants who gave written informed consent. Patients (n=211) were followed up
      on by their general practitioners (GPs) (n=42) during one year. All relatives
      were invited, and 173 (82%) agreed and participated. A questionnaire created by
      the authors was used. The data were analyzed by frequency distribution
      (descriptive statistics) and nonparametric tests (Pearson's chi(2)) and
      statistically processed using SPSS 17.0 (SPSS Inc., Chicago, IL). RESULTS:
      Relatives providing care were predominantly women, two-thirds over 60 years of
      age. There was a one-to-one ratio between caregivers for oncological and
      nononcological patients. The duration of care was more than one year in 53% of
      cases. Most relatives reported their loved ones found physical suffering "very
      hard to bear" (53%), while approximately 17% could not assess the extent of
      psychological suffering. The vast majority stated that they had difficulties in
      providing care, and 68% had financial problems in that respect. CONCLUSION:
      Including relatives as users and part of the palliative care team has been
      discussed in the literature. In Bulgaria, participation is solely due to the lack
      of organized services for palliative care. Relatives participate in activities
      that are performed by trained staff in countries with developed palliative care;
      these activities, along with negative emotional experiences and economic
      difficulties, overburden these caregiving relatives significantly.

PMID- 24320121
TI  - Elemental bioimaging of nanosilver-coated prostheses using X-ray fluorescence
      spectroscopy and laser ablation-inductively coupled plasma-mass spectrometry.
AB  - The distribution of different chemical elements from a nanosilver-coated bone
      implant was visualized, combining the benefits of two complementary methods for
      elemental bioimaging, the nondestructive micro X-ray fluorescence (MU-XRF), and
      laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).
      Challenges caused by the physically inhomogeneous materials including bone and
      soft tissues were addressed by polymer embedding. With the use of MU-XRF, fast
      sample mapping was achieved obtaining titanium and vanadium signals from the
      metal implant as well as phosphorus and calcium signals representing hard bone
      tissue and sulfur distribution representing soft tissues. Only by the use of LA
      ICP-MS, the required high sensitivity and low detection limits for the
      determination of silver were obtained. Metal distribution within the part of
      cancellous bone was revealed for silver as well as for the implant constituents
      titanium, vanadium, and aluminum. Furthermore, the detection of coinciding high
      local zirconium and aluminum signals at the implant surface indicates remaining
      blasting abrasive from preoperative surface treatment of the nanosilver-coated
      device. 

PMID- 24320122
TI  - The first 5 years of Bioanalysis: a story of growth and evolution.

PMID- 24320123
TI  - How has screening of harmful drinking changed over the years?

PMID- 24320125
TI  - Conference report: hot topics in antibody-drug conjugate development.
AB  - American Association of Pharmaceutical Scientists National Biotechnology
      Conference Sheraton San Diego Hotel and Marina, San Diego, CA, USA, 19-23 May
      2013 The National Biotechnology Conference, is a premier meeting for
      biotechnology professionals covering a broad range of hot topics in the
      biotechnology industry. Attracting participants from academia, industry and
      regulatory, this meeting features sessions that aim to address emerging subjects
      of interest and allows for open exchange between scientists. The 2013 conference
      featured leading researchers in the fields of antibody-drug conjugates (ADCs) and
      immunogenicity. Herein, we present a summary of the ADC hot topics, including
      bioanalytical and PK considerations, quantitative evaluation of the impact of
      immunogenicity and ADME to understand ADC drug-drug interactions, and clinical
      considerations for ADC development. This article aims to summarize the
      recommendations that were made by the speakers during various sessions throughout
      the conference. 

PMID- 24320126
TI  - Detection and quantification of dermorphin and selected analogs in equine urine.
AB  - BACKGROUND: Dermorphin, a hepta-peptide with potent analgesic properties, is
      classified as a doping agent in equine racing. Since its discovery, a number of
      biologically active structural analogs have been synthesized and made
      commercially available so there is a need for reliable methods of detection.
      METHODOLOGY/RESULTS: A sensitive detection method was developed for dermorphin
      and six analogs in equine urine. Peptide enrichment was achieved using weak
      cation exchange with subsequent separation and detection by nano-UHPLC-MS/MS.
      Method validation parameters included: specificity, linearity (5-10000 pg/ml),
      recovery (58-93%), intra and inter-assay repeatability, LOD (5-50 pg/ml) and
      matrix effects. CONCLUSION: The presented method will facilitate the control of
      the abuse of dermorphin and selected analogs in equine sports.

PMID- 24320128
TI  - Folate determination in human health: UPLC-MS/MS is the emerging methodology of
      choice.
AB  - This Perspective provides a brief description of the essential role that folates
      play in human health, together with an overview of the various analytical methods
      that have been used for quantitation of folates in human populations over the
      past few decades. Essentially, folate methodology has evolved from
      microbiological assay-based, to binding-based technology and, more recently, to
      separation-based methodology. Separation-based methods initially used traditional
      LC in conjunction with various detection techniques, with the most recent methods
      utilizing UPLC-MS/MS. Current UPLC methods offer exceptional speed, sensitivity
      and quantitation ability for the monoglutamate folate isoforms. It appears that
      the only limitation to properly quantifying all folates as polyglutamates, some
      40-50 species, is the current lack of corresponding stable-isotope standards.
      Clearly, UPLC-MS/MS is emerging as the 'method of choice' for the determination
      of folates, whether in support of basic research, clinical investigations or
      population studies. 

PMID- 24320127
TI  - Human platelets as a platform to monitor metabolic biomarkers using stable
      isotopes and LC-MS.
AB  - BACKGROUND: Intracellular metabolites such as CoA thioesters are modulated in a
      number of clinical settings. Their accurate measurement from surrogate tissues
      such as platelets may provide additional information to current serum and urinary
      biomarkers. METHODS: Freshly isolated platelets from healthy volunteers were
      treated with rotenone, propionate or isotopically labeled metabolic tracers.
      Using a recently developed LC-MS-based methodology, absolute changes in short
      chain acyl-CoA thioesters were monitored, as well as relative metabolic labeling
      using isotopomer distribution analysis. RESULTS: Consistent with in vitro
      experiments, isolated platelets treated with rotenone showed decreased
      intracellular succinyl-CoA and increased beta-hydroxybutyryl-CoA, while
      propionate treatment resulted in increased propionyl-CoA. In addition,
      isotopomers of the CoAs were readily detected in platelets treated with the
      [(13)C]- or [(13)C(15)N]-labeled metabolic precursors. CONCLUSION: Here, we show
      that human platelets can provide a powerful ex vivo challenge platform with
      potential clinical diagnostic and biomarker discovery applications.

PMID- 24320129
TI  - The bioanalytical challenge of determining unbound concentration and protein
      binding for drugs.
AB  - Knowledge regarding unbound concentrations is of vital importance when exploring
      the PK and PD of a drug. The accurate and reproducible determination of plasma
      protein binding and unbound concentrations for a compound/drug is a serious
      challenge for the bioanalytical laboratory. When the drug is in equilibrium with
      the binding protein(s), this equilibrium will shift when physiological conditions
      are not met. Furthermore, the true unbound fraction/concentration is unknown, and
      there are numerous publications in the scientific literature reporting and
      discussing data that have been produced without sufficient control of the
      parameters influencing the equilibrium. In this Review, different parameters
      affecting the equilibrium and analysis are discussed, together with suggestions
      on how to control these parameters in order to produce as trustworthy results for
      unbound concentrations/fractions as possible. 

PMID- 24320130
TI  - Alternative sample diluents in bioanalytical LC-MS.
AB  - The problem of sample diluent in bioanalytical LC-MS is reviewed with a special
      focus on large-volume injections and non-miscible solvents with mobile phase
      components. These issues are related to the sample preparation approach, which in
      many instances provides the sample diluent before injecting this into the
      chromatographic column. The sample volume influences the quantitation limit of
      the chromatographic method, while its nature may influence the retention process
      of the injected analytes. The literature reports a few papers that are focused on
      alternative sample diluents in bioanalytical LC-MS that are generally non
      miscible with mobile phase. The principle of this approach and some of its
      current bioanalytical applications from literature are discussed. However, more
      applications and more publications from HPLC users and vendors are expected in
      this field, which could prove its analytical importance and potential in
      bioanalysis. 

PMID- 24320131
TI  - Recent trends in the determination of vitamin D.
AB  - The occurrence of vitamin D deficiency has become an issue of serious concern in
      the worldwide population. As a result numerous analytical methods have been
      developed, for a variety of matrices, during the last few years to measure
      vitamin D analogs and metabolites. This review employs a comprehensive search of
      all vitamin D methods developed during the last 5 years for all applications,
      using ISI Web of Science((r)), Scifinder((r)), Science Direct, Scopus and PubMed.
      Particular emphasis is given to sample-preparation methods and the different
      forms of vitamin D measured across different fields of applications such as
      biological fluids, food and pharmaceutical preparations. This review compares and
      critically evaluates a wide range of approaches and methods, and hence it will
      enable readers to access developments across a number of applications and to
      select or develop the optimal analytical method for vitamin D for their
      particular application. 

PMID- 24320132
TI  - Rapid diagnosis of TB using GC-MS and chemometrics.
AB  - The search continues for a rapid diagnostic test for TB that has high sensitivity
      and specificity and is useable in sophisticated environments and in deprived
      regions with poor infrastructure. We discuss here the modern bioanalytical
      techniques that can be used to discover biomarkers of infection with
      Mycobacterium tuberculosis, focusing on techniques using GC. We will also discuss
      the use of GC-MS to identify volatile organic compounds in the headspace of
      bacterial culture or in samples of breath, serum or urine. Biomarkers discovered
      in the 'clean' environment of culture may differ from those in patients. A number
      of biomarkers have been found in patients, with little consistency in the various
      studies to date. Reproducibility is difficult; the impressive results found
      initially with a few patients are rarely repeatable when a larger sample series
      is tested. Mycobacterial lipids offer promise for distinguishing M. tuberculosis
      from nontuberculous mycobacteria directly in sputum. 

PMID- 24320134
TI  - Role of FGF10 on tumorigenesis by MS-K.
AB  - Murine MS-K and NFSA cell lines formed tumor after inoculation into mouse and
      both cell lines expressed high level of vascular endothelial growth factor-A
      (vegf-A) and produced same level of VEGF-A. However, poor blood vessel formation,
      and necrosis was significantly observed in NFSA-tumor, contrary to well-developed
      blood vessel formation in MS-K tumor. The microarray analysis showed high
      expression of fibroblast growth factor-10 (fgf-10) in MS-K than NFSA. In this
      report, the role of fgf-10 on tumor growth was studied. MS-K enhanced more
      proliferation of endothelial cells by direct co-culture than NFSA, and rFGF10
      supported the proliferation of HUVEC in combination with VEGF-A. fgf-10-knocked
      down MS-K, MS-K (fgf-10-KD), proliferated slower in vitro and the tumorigenicity
      of them was also slower than control. The blood vessel formation in these MS-K
      (fgf-10-KD) clones was reduced compared with the MS-K (normal). qPCR analysis
      showed the suppression of vegf-A, vegf-C and fgfr-1-expression in the MS-K (fgf
      10-KD) clones. Taken together, these results indicated that FGF10, which was
      produced from tumor cells, was essential for the proliferation of tumor cell
      itself and also supports proliferation of endothelial cells. Thus, FGF10 plays an
      important role for tumor growth by both paracrine and autocrine manner.

PMID- 24320135
TI  - 6-Phosphorylated phenanthridines from 2-isocyanobiphenyls via radical C-P and C-C
      bond formation.
AB  - A C-P bond and a C-C bond are formed in the synthesis of 6-phosphorylated
      phenanthridines starting with readily prepared 2-isocyanobiphenyls and
      commercially available P-radical precursors. The radical cascade reaction
      comprises addition of an oxidatively generated P-centered radical to the
      isonitrile functionality and subsequent homolytic aromatic substitution. Various
      6-phosphorylated phenanthridines are formed in moderate to excellent yield. In
      contrast to the currently intensively investigated direct arene phosphorylation,
      the arene core is constructed with concomitant phosphorylation using this
      approach. 

PMID- 24320136
TI  - Carotid artery remodelling in relation to body fat distribution, inflammation and
      sustained weight loss in obesity.
AB  - BACKGROUND: Obesity is known to be associated with carotid artery remodelling,
      but less is known about how body fat distribution, inflammation and weight loss
      may affect this relation. METHODS: Ultrasonography, dual-energy X-ray
      absorptiometry and computed tomography were performed to evaluate carotid artery
      intima-media thickness (IMT), body composition and fat distribution,
      respectively. Participants were divided into three matched study groups (n = 44
      per group): obese patients with sustained weight loss 10 years after bariatric
      surgery [surgery group, body mass index (BMI) 31.5 kg m(-2)]; obese patients who
      maintained stable weight during the same time period (obese group, BMI 42.5 kg m(
      2)); and normal weight subjects (lean group, BMI 24.4 kg m(-2)). RESULTS:
      Patients in the surgery group, compared with those in the obese group, had
      slightly lower common carotid artery (CCA) IMT (0.75 +/- 0.18 vs. 0.78 +/- 0.17
      mm) and common carotid bulb (CCB) IMT (0.92 +/- 0.32 vs. 0.97 +/- 0.32 mm);
      however, these differences were not statistically significant. Lean individuals,
      compared with those in the surgery group, had significantly lower CCA and CCB IMT
      values (P < 0.001). In forward stepwise multiple regression analyses including
      all subjects (n = 132), CCA IMT was predicted mainly by visceral adipose tissue,
      but was also related to blood pressure and levels of triglycerides and high
      sensitivity C-reactive protein. Carotid lumen diameter was primarily influenced
      by lean body mass. CONCLUSION: Visceral adiposity was the main determinant of
      premature carotid artery atherosclerosis, possibly through elevated blood
      pressure, dyslipidaemia and inflammation. Lean body mass predicted carotid artery
      lumen diameter. Obese patients with long-term sustained weight loss did not have
      thinner carotid artery walls compared with their weight-stable obese
      counterparts.

PMID- 24320137
TI  - A processing fluency-account of funniness: running gags and spoiling punchlines.
AB  - Earlier theories on humour assume that funniness stems from the incongruity
      resolution of the surprising punchline and thus an insight into the joke's
      meaning. Applying recent psychological theorising that insight itself draws on
      processing fluency being the ease and speed with which mental content is
      processed, it is predicted that increasing the fluency of processing the
      punchline of a joke increases funniness. In Experiments 1 and 2, significant
      nouns from the punchlines or from the beginnings of jokes were presented before a
      joke was rated in funniness. Pre-exposing punchline words 15 minutes and even
      only 1 minute before the eventual joke led to increased funniness ratings. In
      contrast, pre-exposing punchline words directly before a joke led to decreased
      funniness ratings. Furthermore, pre-exposing the beginning of a joke 1 minute
      before the joke had no effects on funniness. Experiment 3 ruled out exposure
      facilitated punchline anticipation as alternative mechanism, and Experiment 4
      replicated this fluency effect with typing font as manipulation. These findings
      also show that pre-exposing a punchline, which in common knowledge should spoil a
      joke, can actually increase funniness under certain conditions. 

PMID- 24320138
TI  - Accumulation of perfluoroalkyl compounds in tibetan mountain snow: temporal
      patterns from 1980 to 2010.
AB  - The use of snow and ice cores as recorders of environmental contamination is
      particularly relevant for per- and polyfluoroalky substances (PFASs) given their
      production history, differing source regions and varied mechanisms driving their
      global distribution. In a unique study perfluoroalkyl acids (PFAAs) were analyzed
      in dated snow-cores obtained from high mountain glaciers on the Tibetan Plateau
      (TP). One snow core was obtained from the Mt Muztagata glacier (accumulation
      period of 1980-1999), located in western Tibet and a second core from Mt.
      Zuoqiupo (accumulation period: 1996-2007) located in southeastern Tibet, with
      fresh surface snow collected near Lake Namco in 2010 (southern Tibet). The higher
      concentrations of ?PFAAs were observed in the older Mt Muztagata core and
      dominated by perfluorooctanesulfonic acid (PFOS) (61.4-346 pg/L) and
      perfluorooctanoic acid (PFOA) (40.8-243 pg/L), whereas in the Mt Zuoqiupu core
      the concentrations were lower (e.g., PFOA: 37.8-183 pg/L) with PFOS below
      detection limits. These differences in PFAA concentrations and composition
      profile likely reflect the upwind sources affecting the respective sites (e.g.,
      European/central Asian sources for Mt Muztagata and India sources for Mt
      Zuoqiupu). Perfluorobutanoic acid (PFBA) dominated the recent surface snowpack of
      Lake Namco which is mainly associated with India sources where the shorter chain
      volatile PFASs precursors predominate. The use of snow cores in different parts
      of Tibet provides useful recorders to examine the influence of different PFASs
      source regions and reflect changing PFAS production/use in the Northern
      Hemisphere. 

PMID- 24320139
TI  - Chemopreventive effect of quercetin in MNU and testosterone induced prostate
      cancer of Sprague-Dawley rats.
AB  - Prostate cancer becomes an ideal target for chemoprevention because of its high
      incidence and extended natural history. The consumption of quercetin (plant
      flavonoid) in diet is associated with decreased risk of disease and many cancers
      but then this was not elucidated in prostate malignancy. Hence, a study in which
      the male Sprague-Dawley rats were induced prostate cancer by hormone
      (testosterone) and carcinogen (MNU) and simultaneously supplemented with
      quercetin (200 mg/Kg body weight) thrice a week, was conducted. After the
      treatment period, rats were killed; ventral and dorsolateral lobes of the
      prostate were dissected. Histology and oxidative stress markers LPO, H2O2, and
      antioxidant GSH level were measured in both lobes. The lipid peroxidation, H2O2,
      in (MNU+T) treated rats were increased and GSH level was decreased, whereas
      simultaneous quercetin-treated rats reverted back to normal level in both ventral
      and dorsolateral regions. The different patterns of PIN were observed with
      associated hyperplasia and dysplasia; changes in these regions and the occurrence
      of this lesion were reduced in simultaneous quercetin-treated rats. The study
      concluded that dietary quercetin prevented MNU + T-induced prostate
      carcinogenesis on both ventral and dorsolateral lobes of Sprague-Dawley rats. 

PMID- 24320140
TI  - Tinea versicolor in dark-skinned individuals.
AB  - In this article, we review the salient features of tinea versicolor and describe
      the epidemiology, clinical presentation, and histopathology of this mycosis in
      dark-skinned individuals. Tinea versicolor is caused by an overgrowth of the
      Malassezia genus. It manifests clinically as asymptomatic hypopigmented macules,
      hyperpigmented macules, or a combination of the two. Under light microscopy,
      Malassezia presents as a dimorphic fungus - in both the hyphal and yeast form.
      Most clinicians have found that the majority of dark-skinned patients present
      solely with hypopigmented lesions. Under light microscopy, lesions on dark skin
      involved with tinea versicolor tend to have a thicker stratum corneum, more
      tonofilaments in the granulosum, and more sequestered melanosomes. Differential
      diagnosis includes confluent and reticulated papillomatosis, seborrheic
      dermatitis, pityriasis rosea, pityriasis alba, and vitiligo. Tinea versicolor can
      be successfully managed in most cases with topical antifungal treatments. Cases
      of recurrence, such as those seen in immunocompromised patients, may necessitate
      scheduled oral or topical therapy. 

PMID- 24320142
TI  - Current status of antiangiogenic therapies for glioblastomas.
AB  - INTRODUCTION: Glioblastoma (GBM), the most common primary malignant brain tumor
      in adults, lacks effective long-term treatment. The tumor is dependent on
      neovascularization for survival, making angiogenesis an attractive target for
      therapeutic intervention. The exact mechanism underlying the effects of
      antiangiogenic agents on GBM remains debatable, although it likely involves
      vascular endothelial growth factor (VEGF), and other proangiogenic growth
      factors. Early studies in the recurrent GBM setting were promising and prompted
      two multinational randomized phase three trials (AVAglio and RTOG 0825)
      investigating the effect of bevacizumab, an anti-VEGF monoclonal antibody, in
      newly diagnosed GBM. AREAS COVERED: In this article, the authors discuss the
      basic mechanisms of angiogenesis and antiangiogenic resistance. The authors
      additionally summarize the current state of clinical research and how it will
      impact both future research and the development antiangiogenic therapies. EXPERT
      OPINION: The ultimate utility of antiangiogenic therapy in the management of GBM
      remains unclear. In an effort to improve outcomes, there remains an urgent need
      to better understand the biology underlying angiogenesis and tumor survival, as
      well as mechanisms of antiangiogeneic resistance. Ultimately, combinatorial
      approaches using antiangiogenic agents, targeted molecular therapy, immunotherapy
      or cytotoxics may be needed to improve treatment outcomes.

PMID- 24320141
TI  - Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in
      pre-menopausal women.
AB  - BACKGROUND: Low serum vitamin D levels have been associated with several
      autoimmune diseases, but their association with thyroid autoimmunity is unclear.
      We evaluated the association of serum vitamin D levels with the prevalence of
      autoimmune thyroid disease (AITD). METHODS: Our cross-sectional study included
      subjects who underwent routine health checkups, which included assays of serum 25
      hydroxy vitamin D3 [25(OH)D3] and anti-thyroid peroxidase antibody (TPO-Ab), as
      well as thyroid ultrasonography (US) between 2008 and 2012 at the Asan Medical
      Center. We defined AITD according to the levels of TPO-Ab and US findings.
      RESULTS: A total of 6685 subjects (58% male; 42% female) were enrolled for this
      study. Overall prevalence of TPO-Ab positivity and both TPO-Ab/US positivity were
      10.1% (6.3% male; 15.3% female) and 5.4% (2.3% male; 9.7% female) respectively.
      In female subjects, mean serum 25(OH)D3 levels were significantly lower in the
      TPO-Ab(+) (22.0 vs. 23.5 ng/mL, p=0.030) and TPO-Ab(+)/US(+) groups (21.6 vs.
      23.4 ng/mL, p=0.027) compared with the control group, respectively. According to
      the levels of serum 25(OH)D3, the prevalence of TPO-Ab positivity (21.2%, 15.5%,
      and 12.6% in deficient, insufficient, and sufficient group, respectively;
      p=0.001) and both TPO-Ab and US positivity (14.7%, 9.9%, and 7.1% in deficient,
      insufficient, and sufficient group, respectively; p<0.001) decreased in female
      subjects. Interestingly, this pattern was significant only in pre-menopausal
      women (p=0.003 and p<0.001; respectively), but not in postmenopausal women.
      Multivariate analysis indicated that the adjusted odds ratios (OR) for AITD among
      those in the 25(OH)D3-deficient [TPO-Ab(+): OR 1.95, p=0.001; TPO-Ab(+)/US(+): OR
      2.36, p<0.001] and -insufficient groups [TPO-Ab(+): OR 1.31, p=0.043; TPO
      Ab(+)/US(+): OR 1.50, p=0.017] were significantly increased when compared with
      the sufficient group. CONCLUSIONS: The levels of serum vitamin D were
      significantly lower in pre-menopausal women with AITD. Vitamin D deficiency and
      insufficiency were significantly associated with AITD in pre-menopausal women.

PMID- 24320143
TI  - Ligand-based virtual screening to predict inhibitors against metastatic lymph
      node 64.
AB  - Conversion of cholesterol to pregnenolone is the rate-limiting step in
      steroidogenesis, which is mediated by StAR protein. The mammalian genome contains
      15 START domain proteins (StARD1-StARD15) of which C-terminal cytosolic START
      domain of metastatic lymph node 64 (MLN64 or StARD3), is known to mobilize
      cholesterol and proposed to participate in steroidogenesis. Being a key in
      steroidogenesis, it is of interest to identify new inhibitors that are able to
      bind MLN64 protein. In the present study, we used ligand-based virtual screening
      approach to identify ligands from the ZINC database with D(-)-Tartaric Acid (TAR)
      serving as a template.

PMID- 24320144
TI  - Distinct signaling pathways leading to the induction of human beta-defensin 2 by
      stimulating an electrolyticaly-generated acid functional water and double strand
      RNA in oral epithelial cells.
AB  - Defensins, a major family of cationic antimicrobial peptides, play important
      roles in innate immunity. In the present study, we investigated whether double
      stranded RNA (dsRNA), a by-product of RNA virus replication, can induce human
      beta-defensins-2 (hBD-2) expression in oral epithelial cells (OECs). We also
      examined the hBD-2-inducible activity of acid-electrolyzed functional water (FW).
      The results indicated that both dsRNA- and FW-induced hBD-2 expression in OECs.
      The induction efficiency was much higher for FW than for dsRNA. FW-induced
      production of hBD-2 was clearly observed by immunofluorescence staining. A
      luciferase assay was performed with 1.2 kb of the 5'-untranslated region (5'-UTR)
      of the hBD-2 gene. The results indicated that the nuclear factor-kappa B (NF
      kappaB)-binding site proximal to the translation initiation site was
      indispensable for dsRNA-stimulated hBD-2 expression, but not in the case of FW.
      Moreover, FW-stimulated hBD-2 expression did not depend on NF-kappaB activity;
      instead, FW inhibited NF-kappaB activity. Pretreatment of the cells with specific
      inhibitors against NF-kappaB further confirmed NF-kappaB-independent hBD-2
      induction by FW. In analogy to the results for intestinal epithelial cells
      (IECs), the dsRNA signal, but not FW, was sensed by toll-like receptor 3 (TLR3)
      in OECs. These results suggested that hBD-2 expression induced by dsRNA and FW is
      regulated by distinct mechanisms in OECs.

PMID- 24320145
TI  - Evaluation and management of multiple miliary osteoma cutis: case series of 11
      patients and literature review.

PMID- 24320146
TI  - "They were only joking": efforts to decrease LGBTQ bullying and harassment in
      seattle public schools.
AB  - BACKGROUND: Seattle Public Schools has implemented policies and programs to
      increase safety, family involvement, and student achievement for lesbian, gay,
      bisexual, transgender, and questioning (LGBTQ) youth. This case study examines
      students' perceptions of bullying and harassment in the school environment, and
      teacher intervention when these problems arise in the presence of strong district
      policies and programs aimed at reducing LGBTQ bullying and harassment in schools.
      METHODS: We surveyed students in Gay-Straight Alliance (GSA) groups at 13
      secondary schools (N = 107). We also conducted focus groups with GSA students and
      students not involved in the GSAs in 7 of 13 schools (N = 16 groups, including
      154 students). RESULTS: GSA students who were lesbian, gay, bisexual, or
      questioning (LGBQ) were significantly more likely than straight students to
      experience several types of harassment. On the basis of student report, the 2
      most common intervention strategies by teachers for verbal harassment included
      stopping the harassment and explaining why it is wrong; teachers intervened in
      physical harassment by trying to stop the harassment. Students provided input on
      how to strengthen teacher interventions, including the need for more consistency
      in responding and following up. Students also noted a need for more focus on
      educating those who harass, rather than just asking them to stop. CONCLUSIONS:
      Seattle Public Schools has made great strides in creating safe and welcoming
      schools for LGBTQ students, but still have to work further toward reaching this
      goal. Data from students on how they experience their school environment can help
      identify areas for improvement.

PMID- 24320147
TI  - New evidence: data documenting parental support for earlier sexuality education.
AB  - BACKGROUND: Numerous studies document support for sexuality education to be
      taught in high school, and often, in middle school. However, little research has
      been conducted addressing support for sexuality education in elementary schools.
      METHODS: As part of the state Behavioral Risk Factor Surveillance System (BRFSS)
      Survey administration, the Florida Department of Health conducted the Florida
      Child Health Survey (FCHS) by calling back parents who had children in their home
      and who agreed to participate (N = 1715). RESULTS: Most parents supported the
      following sexuality education topics being taught specifically in elementary
      school: communication skills (89%), human anatomy/reproductive information (65%),
      abstinence (61%), human immunodeficiency virus (HIV)/sexually transmitted
      infections (STIs) (53%), and gender/sexual orientation issues (52%). Support was
      even greater in middle school (62-91%) and high school (72-91%) for these topics
      and for birth control and condom education. Most parents supported comprehensive
      sexuality education (40.4%), followed by abstinence-plus (36.4%) and abstinence
      only (23.2%). Chi-square results showed significant differences in the type of
      sexuality education supported by almost all parent demographic variables analyzed
      including sex, race, marital status, and education. CONCLUSIONS: Results add
      substantial support for age-appropriate school-based sexuality education starting
      at the elementary school level, the new National Sexuality Education Standards,
      and funding to support evidence-based abstinence-plus or comprehensive sexuality
      education.

PMID- 24320148
TI  - Survey of new Mexico school health professionals regarding preparedness to
      support sexual minority students.
AB  - BACKGROUND: For schools to be safe and supportive for students, school health
      professionals should be aware of the particular challenges lesbian, gay,
      bisexual, transgender, or questioning (LGBTQ) students face, especially the risk
      for discrimination, violent victimization, and depression in the school setting.
      We assessed school health professionals' preparedness to address needs of LGBTQ
      students. METHODS: We conducted a secondary analysis of data collected during a
      New Mexico school health conference. This analysis focused on the preparedness of
      183 school nurses, counselors, and social workers to address needs of LGBTQ
      students. Data were analyzed by using chi-square tests, other non-parametric
      tests, and logistic regression. RESULTS: Social workers (84.6%) and counselors
      (81.5%) were more likely than school nurses (55.8%) to report moderate or high
      knowledge of LGBTQ youth health risks, including suicide and depression (p <
      .001). Approximately half of school counselors and social workers reported no or
      low knowledge of LGBTQ community-based organizations or knowledge of counselors
      experienced with LGBTQ concerns. CONCLUSION: School health professionals in New
      Mexico do not appear prepared to address needs of LGBTQ students. Schools should
      consider integrating specific content about LGBTQ health risks and health
      disparities in trainings regarding bullying, violence, cultural competency, and
      suicide prevention.

PMID- 24320149
TI  - Substance use and sexual risk behaviors among american Indian and alaska native
      high school students.
AB  - BACKGROUND: We describe the prevalence of behaviors that put American Indian and
      Alaska Native (AI/AN) high school students at risk for teen pregnancy and
      sexually transmitted infections (STIs) and the relationships among race/ethnicity
      and these behaviors. METHODS: We analyzed merged 2007 and 2009 data from the
      national Youth Risk Behavior Survey, a biennial, self-administered, school-based
      survey of US students in grades 9-12 (N = 27,912). Prevalence estimates and
      logistic regression, controlling for sex and grade, were used to examine the
      associations between race/ethnicity, and substance use, and sexual risk
      behaviors. RESULTS: Of the 26 variables studied, the adjusted odds ratios (AOR)
      were higher among AI/AN than White students for 18 variables (ranging from 1.4 to
      2.3), higher among AI/AN than Black students for 13 variables (ranging from 1.4
      to 4.2), and higher among AI/AN than Hispanic students for 5 variables (ranging
      from 1.4 to 1.5). Odds were lower among AI/AN than Black students for many of the
      sexual risk-related behaviors. CONCLUSIONS: The data suggest it is necessary to
      develop targeted, adolescent-specific interventions aimed at reducing behaviors
      that put AI/AN high school students at risk for teen pregnancy, STI/HIV, and
      other health conditions.

PMID- 24320150
TI  - Associations among text messaging, academic performance, and sexual behaviors of
      adolescents.
AB  - BACKGROUND: Text messaging is an increasingly common mode of communication,
      especially among adolescents, and frequency of texting may be a measure of one's
      sociability. This study examined how text messaging ("texting") frequency and
      academic performance are associated with adolescent sexual behaviors. METHODS: A
      cross-sectional survey was administered to students at a public charter high
      school in Los Angeles County, CA. Two hundred fifty-six high school students aged
      14-20 years participated. Outcome measures were history of vaginal sex, condom
      use, and worries about pregnancy. The main predictors were text messaging
      frequency and self-reported academic performance. RESULTS: In general, students
      with lower grades were more likely to have had vaginal sex. Greater texting
      frequency, however, was associated with vaginal sex only among students with
      higher grades. In addition, despite similar rates of condom use, sexually active
      students who both had good grades and texted frequently were more likely than
      others to have thought they or their partner might be pregnant. CONCLUSIONS: The
      association between texting and sexual behaviors may vary based on adolescent's
      academic performance. Adolescent sexual health interventions may benefit from
      using a combination of sociability measures (such as texting frequency) and
      academic performance as risk predictors.

PMID- 24320152
TI  - Relationship of weight-based teasing and adolescents' psychological well-being
      and physical health.
AB  - BACKGROUND: To date, research has focused primarily on psychological correlates
      of weight-based teasing. In this study, we extended previous work by also
      examining physical health-related variables (eg, physical self-concept and
      physical fitness [PF]). METHODS: Participants included 1419 middle school
      students (637 boys and 782 girls). Of these, 245 (17.3%) reported being teased
      about being overweight. Participants completed measures of self-esteem,
      depression, physical self-concept, physical activity (PA) self-efficacy, and self
      report physical and sedentary activities. Participants also completed PF testing.
      RESULTS: After controlling for demographic characteristics, participants who were
      teased about being overweight had higher scores on depression and lower scores on
      self-esteem, physical self-concept, PA self-efficacy, and health-related measures
      of PF in comparison to participants who were not teased. CONCLUSIONS: The results
      of this study support previous research indicating relationships between teasing
      and low levels of psychological well-being, physical self-concept, and PA self
      efficacy, and establishes one between weight-based teasing and different types of
      PF. Research is needed to determine the potential causal nature of the
      relationships between teasing and fitness and evidence-based interventions are
      needed to reduce weight-based teasing and its potential effects on health and
      well-being.

PMID- 24320151
TI  - Health and academic achievement: cumulative effects of health assets on
      standardized test scores among urban youth in the United States.
AB  - BACKGROUND: The Institute of Medicine (2012) concluded that we must "strengthen
      schools as the heart of health." To intervene for better outcomes in both health
      and academic achievement, identifying factors that impact children is essential.
      Study objectives are to (1) document associations between health assets and
      academic achievement, and (2) examine cumulative effects of these assets on
      academic achievement. METHODS: Participants include 940 students (grades 5 and 6)
      from 12 schools randomly selected from an urban district. Data include physical
      assessments, fitness testing, surveys, and district records. Fourteen health
      indicators were gathered including physical health (eg, body mass index [BMI]),
      health behaviors (eg, meeting recommendations for fruit/vegetable consumption),
      family environment (eg, family meals), and psychological well-being (eg, sleep
      quality). Data were collected 3-6 months prior to standardized testing. RESULTS:
      On average, students reported 7.1 health assets out of 14. Those with more health
      assets were more likely to be at goal for standardized tests
      (reading/writing/mathematics), and students with the most health assets were 2.2
      times more likely to achieve goal compared with students with the fewest health
      assets (both p < .001). CONCLUSIONS: Schools that utilize nontraditional
      instructional strategies to improve student health may also improve academic
      achievement, closing equity gaps in both health and academic achievement.

PMID- 24320153
TI  - Factors influencing school closure and dismissal decisions: influenza A (H1N1),
      Michigan 2009.
AB  - BACKGROUND: In fall 2009, many US communities experienced school closures during
      the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567
      closures. We conducted an investigation in Michigan to describe pH1N1-related
      school policies, practices, and identify factors related to school closures.
      METHODS: We distributed an online survey to all Michigan K-12 school principals.
      Descriptive statistics and chi-square tests summarize school policies, practices,
      adherence to government guidelines, and differences between schools that closed
      and those that remained open during the pandemic. RESULTS: Of 4441 traditional K
      12 Michigan schools, 937 (21%) principals responded to our survey representing
      approximately 374,000 students and 17,700 teachers. The majority (88%) of schools
      had influenza preparedness plans and followed government school influenza
      guidelines. Among respondents, 15% (137/937) of schools closed in fall 2009 with
      high absenteeism as the primary reason for closure. Schools that closed reported
      significant illness in their school, had <300 students, and had invested
      substantial resources preparing and responding to influenza. CONCLUSIONS:
      Adherence to government guidelines for schools appears high in Michigan. Closures
      occurred in schools that reported significant illness and were likely motivated
      by excessive absenteeism. Understanding factors related to closures during pH1N1
      may inform future pandemic preparedness efforts.

PMID- 24320154
TI  - Learning from successful school-based vaccination clinics during 2009 pH1N1.
AB  - BACKGROUND: The 2009 H1N1 vaccination campaign was the largest in US history.
      State health departments received vaccines from the federal government and sent
      them to local health departments (LHDs) who were responsible for getting vaccines
      to the public. Many LHD's used school-based clinics to ensure children were the
      first to receive limited vaccine supplies, but the success of school-based
      distribution strategies varied in different locations. The goal of this project
      was to identify and learn from high-performing school-based vaccination clinics
      in order to share successes and improve performance in future school-based
      vaccination campaigns. METHODS: We used a combination of process mapping and
      comparative analysis to identify and derive lessons from positive outlier cases
      observed during 2009 H1N1 school-based vaccination clinic implementation. We
      created process maps to identify the activities of LHDs conducting school-based
      vaccinations and used them as the basis for in-depth interviews of LHD staff. We
      asked interviewees to describe their activities during the 2009 H1N1 pandemic
      (pH1N1) school-based vaccination campaign with a focus on successful processes.
      RESULTS: We identified positive deviants, that is, those that performed better
      than expected, and categorized qualitative data from in-depth interviews with 13
      successful LHDs according to the process maps. Key mechanisms for school-based
      vaccination success included having a relationship with local school authorities,
      communicating effectively with parents, and ensuring clinic logistics allowed for
      an easy flow of students through the vaccination process. CONCLUSIONS: Utilizing
      rigorous methodology, we defined and learned lessons from successful LHDs when
      conducting school-based vaccination clinics, which can be applied to future
      school-based vaccination campaigns.

PMID- 24320155
TI  - I know who my friends are, but do you? Predictors of self-reported and peer
      inferred relationships.
AB  - Using social network data, this study examines which features of social and
      spatial proximity predict self-reported, or "real," and peer-reported, or
      "inferred," relationships among 2,695 pairwise combinations of African American
      second- through fourth-grade students (aged 7-11). Relationships were more likely
      to exist, and more likely to be inferred to exist by peers, between pairs of
      children who were the same sex, sat near one another, shared a positive academic
      orientation, or shared athletic ability. Sex similarity had a dramatically larger
      effect on peers' inferences about relationships than on self-reported real
      relationships, suggesting that children overestimate the importance of gender in
      their inferences about relationships. Results were stable across different grade
      levels in middle childhood and for boys and girls. 

PMID- 24320157
TI  - Atomic structure of an ultrathin Fe-silicate film grown on a metal: a monolayer
      of clay?
AB  - Ultrathin Fe-doped silicate films were prepared on a Ru(0001) surface and, as a
      function of the Fe/Si ratio, structurally characterized by low-energy electron
      diffraction, X-ray photoelectron spectroscopy, infrared reflection-absorption
      spectroscopy, and scanning tunneling microscopy. Density functional theory (DFT)
      was used to identify the atomic structure. The results show that uniform
      substitution of Si by Fe in the silicate bilayer frame is thermodynamically
      unfavorable: the film segregates into a pure silicate and an Fe-silicate phase.
      The DFT calculations reveal that the Fe-silicate film with an Fe/Si = 1:1 ratio
      consists of a monolayer of [SiO4] tetrahedra on top of an iron oxide monolayer.
      As such, it closely resembles the structure of the clay mineral nontronite, a
      representative of the Fe-rich smectites. Furthermore, the DFT calculations
      predict formation of bridging Fe-O-Ru bonds between the Fe-silicate film and the
      Ru substrate accompanied by charge transfer from the metal substrate to the film,
      so that iron is in the oxidation state +III as in nontronite. 

PMID- 24320158
TI  - A review of clinical manifestations in adolescent and young adults after use of
      synthetic cannabinoids.
AB  - PURPOSE: The purpose of this review is to heighten the awareness of the increased
      use and risks of synthetic cannabinoids (SCs) and associated clinical
      manifestations among adolescents and young adults. CONCLUSIONS: Reviewed case
      studies suggest that the use of SCs have unpredictable negative psychological and
      physiological effects. Predominant manifestations reported were anxiety,
      agitation, paranoia, hallucinations, tachycardia, nausea and vomiting, and
      diaphoresis. PRACTICE IMPLICATIONS: Nurses provide the most direct and supportive
      care to patients who present for medical treatment after the use of SCs.
      Knowledge of clinical manifestations can facilitate supportive management of
      patients suspected of SCs use.

PMID- 24320159
TI  - Are bedtime nutritional strategies effective in preventing nocturnal
      hypoglycaemia in patients with type 1 diabetes?
AB  - Hypoglycaemia remains the major limiting factor for adequate diabetes control for
      patients with type 1 diabetes (T1D), especially during the night-time. Although
      nutritional strategies for nocturnal hypoglycaemia (NH) prevention are regularly
      suggested in clinical practice, there is no evidence-based recommendation for the
      usefulness and optimal composition of a bedtime snack. The aim of this narrative
      review was to analyse the current state of knowledge on nutritional strategies to
      prevent NH in individuals with T1D. A literature search was conducted, using
      PubMed and Medline (1946 to 2013); 16 studies were retrieved. Overall, the level
      of evidence was low. Results indicated that a calibrated bedtime snack based on
      bedtime blood glucose (BG) level could be effective to reduce NH occurrence for
      patients treated with human or animal insulin (short-acting combined with lente,
      ultralente and/or intermediate-acting insulin), but there is no evidence for
      patients treated with insulin analogues as part of multiple daily injections or
      insulin pump regimen. Some evidence suggests that including uncooked cornstarch
      or alanine in the bedtime snack composition could provide some benefits for the
      prevention of NH. Individualized recommendations of a bedtime snack intake for
      patients or situations at high risk for NH (long standing diabetes, hypoglycaemia
      unawareness, prior physical activity, alcohol consumption, bedtime BG close to
      hypoglycaemia threshold) appear as a prudent recommendation. On the basis of the
      available evidence, a bedtime snack cannot be recommended systematically but it
      might be useful if prescribed in an individualized fashion; further research is
      needed to evaluate these strategies. 

PMID- 24320156
TI  - DNA transposon-based gene vehicles - scenes from an evolutionary drive.
AB  - DNA transposons are primitive genetic elements which have colonized living
      organisms from plants to bacteria and mammals. Through evolution such parasitic
      elements have shaped their host genomes by replicating and relocating between
      chromosomal loci in processes catalyzed by the transposase proteins encoded by
      the elements themselves. DNA transposable elements are constantly adapting to
      life in the genome, and self-suppressive regulation as well as defensive host
      mechanisms may assist in buffering 'cut-and-paste' DNA mobilization until
      accumulating mutations will eventually restrict events of transposition. With the
      reconstructed Sleeping Beauty DNA transposon as a powerful engine, a growing list
      of transposable elements with activity in human cells have moved into biomedical
      experimentation and preclinical therapy as versatile vehicles for delivery and
      genomic insertion of transgenes. In this review, we aim to link the mechanisms
      that drive transposon evolution with the realities and potential challenges we
      are facing when adapting DNA transposons for gene transfer. We argue that DNA
      transposon-derived vectors may carry inherent, and potentially limiting, traits
      of their mother elements. By understanding in detail the evolutionary journey of
      transposons, from host colonization to element multiplication and inactivation,
      we may better exploit the potential of distinct transposable elements. Hence,
      parallel efforts to investigate and develop distinct, but potent, transposon
      based vector systems will benefit the broad applications of gene transfer.
      Insight and clever optimization have shaped new DNA transposon vectors, which
      recently debuted in the first DNA transposon-based clinical trial. Learning from
      an evolutionary drive may help us create gene vehicles that are safer, more
      efficient, and less prone for suppression and inactivation. 

PMID- 24320161
TI  - Hsa-miR-196a2 functional SNP is associated with the risk of ESCC in individuals
      under 60 years old.
AB  - BACKGROUND AND AIM: The miR-196a2 gene contains a C/T polymorphism (rs11614913).
      Its presence could change the conformation of secondary structure of miR-196a2
      RNA, and directly affect the binding to target mRNAs and the miRNA maturation
      process. Both of which eventually alter protein expression and contributed to
      cancer susceptibility. This study assessed whether the rs11614913 single
      nucleotide polymorphism (SNP) could affect an individual's susceptibility to
      esophageal squamous cell carcinomas (ESCC). METHODS: SNP rs11614913 was genotyped
      by polymerase chain reaction ligase detection reaction (PCR-LDR) in 597 ESCC
      patients and 597 control subjects. RESULTS: Overall, there were no significant
      differences in the frequency of the miRNA-196a2 SNP rs11614913 genotype between
      the ESCC cases and the controls (chi(2) = 1.395, p = 0.498). The TT genotype, CT
      genotype and CT/TT combined genotype (dominant model) did not modify the risk of
      ESCC as compared with the CC genotype. Comparisons of the TT genotype to the
      CT/CC combined genotype did not reveal a significant association to ESCC, too.
      However, further analyses revealed an increased risk of ESCC in the dominant
      model (OR = 1.56, 95% CI = 1.08-2.26) and the allele frequency comparison (OR =
      1.31, 95% CI = 1.06-1.63) in the <=60-year-old group. CONCLUSIONS: These results
      suggest that the miRNA-196a2 functional polymorphism rs11614913 might be an
      effective genetic marker for ESCC risk assessment in individuals younger than 60
      years of age from a region of high ESCC incidence in northern China.

PMID- 24320160
TI  - Profiling substrates of protein arginine N-methyltransferase 3 with S-adenosyl-L
      methionine analogues.
AB  - Protein arginine N-methyltransferase 3 (PRMT3) belongs to the family of type I
      PRMTs and harbors the activity to use S-adenosyl-l-methionine (SAM) as a methyl
      donor cofactor for protein arginine labeling. However, PRMT3's functions remain
      elusive with the lacked knowledge of its target scope in cellular settings.
      Inspired by the emerging Bioorthogonal Profiling of Protein Methylation (BPPM)
      using engineered methyltransferases and SAM analogues for target identification,
      the current work documents the endeavor to systematically explore the SAM-binding
      pocket of PRMT3 and identify suitable PRMT3 variants for BPPM. The M233G single
      point mutation transforms PRMT3 into a promiscuous alkyltransferase using sp(2)
      beta-sulfonium-containing SAM analogues as cofactor surrogates. Here the
      conserved methionine was defined as a hot spot that can be engineered alone or in
      combination with nearby residues to render cofactor promiscuity of multiple type
      I PRMTs. With this promiscuous variant and the matched 4-propargyloxy-but-2-enyl
      (Pob)-SAM analogue as the BPPM reagents, more than 80 novel proteins were readily
      uncovered as potential targets of PRMT3 in the cellular context. Subsequent
      target validation and functional analysis correlated the PRMT3 methylation to
      several biological processes such as cytoskeleton dynamics, whose roles might be
      compensated by other PRMTs. These BPPM-revealed substrates are primarily
      localized but not restricted in cytoplasm, the preferred site of PRMT3. The broad
      localization pattern may implicate the diverse roles of PRMT3 in the cellular
      setting. The revelation of PRMT3 targets and the transformative character of BPPM
      for other PRMTs present unprecedented pathways toward elucidating physiological
      and pathological roles of diverse PRMTs. 

PMID- 24320162
TI  - Multiple MAGE-A genes as surveillance marker for the detection of circulating
      tumor cells in patients with ovarian cancer.
AB  - Ovarian cancer is a leading cause of death among gynecologic malignancies. In
      this study, we reported the expression of melanoma-associated antigens A (MAGE-A)
      genes in peripheral blood from 80 patients with ovarian cancer and 30 healthy
      donors. MAGE-As expression was associated with the factors indicating poor
      prognosis. The expressions of MAGE-As and each individual MAGE-A genes were also
      associated with low overall survival of patients with ovarian cancer. Our results
      suggested MAGE-A genes may have the potential to be surveillance markers for the
      detection of circulating tumor cells and represent a poor prognosis for patients
      with ovarian cancer.

PMID- 24320163
TI  - Tissue-specific alternative splicing analysis reveals the diversity of chromosome
      18 transcriptome.
AB  - The Chromosome-centric Human Proteome Project (C-HPP) is aimed to identify the
      variety of protein products and transcripts of the number of chromosomes. The
      Russian part of C-HPP is devoted to the study of the human chromosome 18. Using
      widely accepted Tophat and SpliceGrapher, a tool for accurate splice sites and
      alternative mRNA isoforms prediction, we performed the extensive mining of the
      splice variants of chromosome 18 transcripts and encoded protein products in
      liver, brain, lung, kidney, blood, testis, derma, and skeletal muscles. About 6.1
      billion of the reads represented by 450 billion of the bases have been analyzed.
      The relative frequencies of splice events as well as gene expression profiles in
      normal tissues are evaluated. Using ExPASy PROSITE, the novel features and
      possible functional sites of previously unknown splice variants were highlighted.
      A set of unique proteotypic peptides enabling the identification of novel
      alternative protein species using mass-spectrometry is constructed. The revealed
      data will be integrated into the gene-centric knowledgebase of the Russian part
      of C-HPP available at http://kb18.ru and http://www.splicing.zz.mu/.

PMID- 24320165
TI  - Improvements in health status after Massachusetts health care reform.
AB  - CONTEXT: Massachusetts enacted health care reform in 2006 to expand insurance
      coverage and improve access to health care. The objective of our study was to
      compare trends in health status and the use of ambulatory health services before
      and after the implementation of health reform in Massachusetts relative to that
      in other New England states. METHODS: We used a quasi-experimental design with
      data from the Behavioral Risk Factor Surveillance System from 2001 to 2011 to
      compare trends associated with health reform in Massachusetts relative to that in
      other New England states. We compared self-reported health and the use of
      preventive services using multivariate logistic regression with difference-in
      differences analysis to account for temporal trends. We estimated predicted
      probabilities and changes in these probabilities to gauge the differential
      effects between Massachusetts and other New England states. Finally, we conducted
      subgroup analysis to assess the differential changes by income and
      race/ethnicity. FINDINGS: The sample included 345,211 adults aged eighteen to
      sixty-four. In comparing the periods before and after health care reform relative
      to those in other New England states, we found that Massachusetts residents
      reported greater improvements in general health (1.7%), physical health (1.3%),
      and mental health (1.5%). Massachusetts residents also reported significant
      relative increases in rates of Pap screening (2.3%), colonoscopy (5.5%), and
      cholesterol testing (1.4%). Adults in Massachusetts households that earned up to
      300% of the federal poverty level gained more in health status than did those
      above that level, with differential changes ranging from 0.2% to 1.3%. Relative
      gains in health status were comparable among white, black, and Hispanic residents
      in Massachusetts. CONCLUSIONS: Health care reform in Massachusetts was associated
      with improved health status and the greater use of some preventive services
      relative to those in other New England states, particularly among low-income
      households. These findings may stem from expanded insurance coverage as well as
      innovations in health care delivery that accelerated after health reform.

PMID- 24320167
TI  - Commentary: "the Lake Wobegon effect, a natural human tendency to overestimate
      one's capabilities" (Wikipedia).

PMID- 24320166
TI  - The Lake Wobegon effect: are all cancer patients above average?
AB  - CONTEXT: When elderly patients face a terminal illness such as lung cancer, most
      are unaware that what we term in this article "the Lake Wobegon effect" taints
      the treatment advice imparted to them by their oncologists. In framing treatment
      plans, cancer specialists tend to intimate that elderly patients are like the
      children living in Garrison Keillor's mythical Lake Wobegon: above average and
      thus likely to exceed expectations. In this article, we use the story of our
      mother's death from lung cancer to investigate the consequences of elderly
      people's inability to reconcile the grave reality of their illness with the
      overly optimistic predictions of their physicians. METHODS: In this narrative
      analysis, we examine the routine treatment of elderly, terminally ill cancer
      patients through alternating lenses: the lens of a historian of medicine who also
      teaches ethics to medical students and the lens of an actuary who is able to
      assess physicians' claims for the outcome of medical treatments. FINDINGS: We
      recognize that a desire to instill hope in patients shapes physicians' messages.
      We argue, however, that the automatic optimism conveyed to elderly, dying
      patients by cancer specialists prompts those patients to choose treatment that is
      ineffective and debilitating. Rather than primarily prolong life, treatments most
      notably diminish patients' quality of life, weaken the ability of patients and
      their families to prepare for their deaths, and contribute significantly to the
      unsustainable costs of the U.S. health care system. CONCLUSIONS: The case
      described in this article suggests how physicians can better help elderly,
      terminally ill patients make medical decisions that are less damaging to them and
      less costly to the health care system.

PMID- 24320168
TI  - Hospital board oversight of quality and patient safety: a narrative review and
      synthesis of recent empirical research.
AB  - CONTEXT: Recurring problems with patient safety have led to a growing interest in
      helping hospitals' governing bodies provide more effective oversight of the
      quality and safety of their services. National directives and initiatives
      emphasize the importance of action by boards, but the empirical basis for
      informing effective hospital board oversight has yet to receive full and careful
      review. METHODS: This article presents a narrative review of empirical research
      to inform the debate about hospital boards' oversight of quality and patient
      safety. A systematic and comprehensive search identified 122 papers for detailed
      review. Much of the empirical work appeared in the last ten years, is from the
      United States, and employs cross-sectional survey methods. FINDINGS: Recent
      empirical studies linking board composition and processes with patient outcomes
      have found clear differences between high- and low-performing hospitals,
      highlighting the importance of strong and committed leadership that prioritizes
      quality and safety and sets clear and measurable goals for improvement. Effective
      oversight is also associated with well-informed and skilled board members.
      External factors (such as regulatory regimes and the publication of performance
      data) might also have a role in influencing boards, but detailed empirical work
      on these is scant. CONCLUSIONS: Health policy debates recognize the important
      role of hospital boards in overseeing patient quality and safety, and a growing
      body of empirical research has sought to elucidate that role. This review finds a
      number of areas of guidance that have some empirical support, but it also exposes
      the relatively inchoate nature of the field. Greater theoretical and
      methodological development is required if we are to secure more evidence-informed
      governance systems and practices that can contribute to safer care.

PMID- 24320169
TI  - Medical home implementation: a sensemaking taxonomy of hard and soft best
      practices.
AB  - CONTEXT: The patient-centered medical home (PCMH) model of care is currently a
      central focus of U.S. health system reform, but less is known about the model's
      implementation in the practice of everyday primary care. Understanding its
      implementation is key to ensuring the approach's continued support and success
      nationally. This article addresses this gap through a qualitative examination of
      the best practices associated with PCMH implementation for older adult patients
      in primary care. METHODS: I used a multicase, comparative study design that
      relied on a sensemaking approach and fifty-one in-depth interviews with
      physicians, nurses, and clinic support staff working in six accredited medical
      homes located in various geographic areas. My emphasis was on gaining descriptive
      insights into the staff's experiences delivering medical home care to older adult
      patients in particular and then analyzing how these experiences shaped the
      staff's thinking, learning, and future actions in implementing medical home care.
      FINDINGS: I found two distinct taxonomies of implementation best practices, which
      I labeled "hard" and "soft" because of their differing emphasis and content. Hard
      implementation practices are normative activities and structural interventions
      that align well with existing national standards for medical home care. Soft best
      practices are more relational in nature and derive from the existing practice
      social structure and everyday interactions between staff and patients. Currently,
      external stakeholders are less apt to recognize, encourage, or incentivize soft
      best practices. CONCLUSIONS: The results suggest that there may be no
      standardized, one-size-fits-all approach to making medical home implementation
      work, particularly for special patient populations such as the elderly. My study
      also raises the issue of broadening current PCMH assessments and reward systems
      to include implementation practices that contain heavy social and relational
      components of care, in addition to the emphasis now placed on building structural
      supports for medical home work. Further study of these softer implementation
      practices and a continued call for qualitative methodological approaches that
      gain insight into everyday practice behavior are warranted.

PMID- 24320173
TI  - Test of long-term uterine survival after allogeneic transplantation in rabbits.
AB  - AIM: To see if: (i) a large vessel aortocaval vascular patch technique may bring
      about long-term graft survival after allogeneic uterine transplantation (UTn) in
      a rabbit model; and (ii) fertility can be achieved following natural mating post
      allogeneic UTn. METHODS: Allogeneic uterine cross transplantations were performed
      in New Zealand white rabbits using an aortocaval macrovascular patch harvested as
      part of the uterine allograft. Five rabbit recipients received a uterine graft
      from five unrelated donor rabbits. All female rabbits were unrelated and were of
      proven fertility with at least one previous litter each. Tacrolimus was
      administrated for immunosuppression post-transplant. Natural mating was attempted
      if long-term survival had been achieved. The main outcome measures were: (i) long
      term recipient survival; (ii) long-term adequate uterine perfusion; and (iii)
      successful pregnancy post-UTn. RESULTS: All five recipient animals survived the
      surgery with satisfactory immediate postoperative recovery. Recipients 1, 2 and 4
      died within the first 4 postoperative days. Both long-term survivors failed to
      conceive following introduction of a proven male breeder despite evidence of
      mating. Necropsy at 9 and 11 months showed a lack of patency of uterine cornua at
      the point of anastomosis, albeit a small uterus in recipient 3 and a reddish
      brown amorphous material at the site of the transplanted uterus in recipient 5.
      CONCLUSION: We have demonstrated the feasibility of uterine allotransplantation
      using a macrovascular patch technique, but could not demonstrate conception
      because of blocked cornua. To address this, we propose using embryo transfer
      techniques in order to achieve conception.

PMID- 24320170
TI  - Behavior change interventions to improve the health of racial and ethnic minority
      populations: a tool kit of adaptation approaches.
AB  - CONTEXT: Adapting behavior change interventions to meet the needs of racial and
      ethnic minority populations has the potential to enhance their effectiveness in
      the target populations. But because there is little guidance on how best to
      undertake these adaptations, work in this field has proceeded without any firm
      foundations. In this article, we present our Tool Kit of Adaptation Approaches as
      a framework for policymakers, practitioners, and researchers interested in
      delivering behavior change interventions to ethnically diverse, underserved
      populations in the United Kingdom. METHODS: We undertook a mixed-method program
      of research on interventions for smoking cessation, increasing physical activity,
      and promoting healthy eating that had been adapted to improve salience and
      acceptability for African-, Chinese-, and South Asian-origin minority
      populations. This program included a systematic review (reported using PRISMA
      criteria), qualitative interviews, and a realist synthesis of data. FINDINGS: We
      compiled a richly informative data set of 161 publications and twenty-six
      interviews detailing the adaptation of behavior change interventions and the
      contexts in which they were undertaken. On the basis of these data, we developed
      our Tool Kit of Adaptation Approaches, which contains (1) a forty-six-item
      Typology of Adaptation Approaches; (2) a Pathway to Adaptation, which shows how
      to use the Typology to create a generic behavior change intervention; and (3)
      RESET, a decision tool that provides practical guidance on which adaptations to
      use in different contexts. CONCLUSIONS: Our Tool Kit of Adaptation Approaches
      provides the first evidence-derived suite of materials to support the
      development, design, implementation, and reporting of health behavior change
      interventions for minority groups. The Tool Kit now needs prospective, empirical
      evaluation in a range of intervention and population settings.

PMID- 24320174
TI  - Development of a novel method for detection of Clostridium difficile using HS
      SPME-GC-MS.
AB  - AIMS: A novel method has been developed that allows successful differentiation
      between Clostridium difficile culture-positive and culture-negative stool samples
      based on volatile organic compound (VOC) evolution and detection by headspace
      solid-phase microextraction coupled with gas chromatography mass spectrometry (HS
      SPME-GC-MS). METHODS AND RESULTS: The method is based on the activation of p
      hydroxyphenylacetate decarboxylase produced by Cl. difficile and the detection of
      a specific VOC, that is 2-fluoro-4-methylphenol from an enzyme substrate. In
      addition, other VOCs were good indicators for Cl. difficile, that is isocaproic
      acid and p-cresol, although they could not be used alone for identification
      purposes. One hundred stool samples were tested, of which 77 were positive by
      culture. Detection using HS-SPME-GC-MS allowed confirmation of the presence of
      Cl. difficile within 18 h with a sensitivity and specificity of 83.1 and 100%,
      respectively. CONCLUSIONS: It is recommended that this new approach could be used
      alongside conventional methods for Cl. difficile detection, including toxin
      detection methods, which would allow any false-negative results to be eliminated.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to identify Cl. difficile
      positive stool samples by the analysis of VOCs could allow the development of a
      VOC detection device which could allow rapid diagnosis of disease and hence
      prompt treatment with appropriate antibiotics.

PMID- 24320175
TI  - Relationship effort, satisfaction, and stability: differences across union type.
AB  - Relationship satisfaction and stability are two commonly studied outcomes in
      marriage and family research. Majority of studies address socio demographic
      variability and differences across union type in these outcomes. We extend this
      literature by addressing how the amount of effort one puts into their
      relationship is associated with stability and satisfaction. Specifically, we
      focus on how effort impacts these measures of quality in four union types:
      premarital cohabitation, first marriage, post-divorce cohabitation, and second
      marriage following divorce. Furthermore, we make union type comparisons in the
      strength of effort's association with satisfaction and stability. Using data from
      8,006 respondents in the Relationship Evaluation Survey, our results show that
      effort was strongly and positively associated with satisfaction and stability in
      all four unions. Although effort is more strongly associated with satisfaction in
      first marriage than cohabiting relationships, no union type differences in the
      role of effort on stability were observed. Clinical and research implications of
      these findings are discussed. 

PMID- 24320177
TI  - Atmospheric helium capillary dielectric barrier discharge for soft ionization:
      determination of atom number densities in the lowest excited and metastable
      States.
AB  - The populations of the lowest excited helium states 2s 3S1, 2s 1S, 2p 3P0 J, and
      2p 1P0 created in an atmospheric helium capillary dielectric barrier discharge
      were determined by means of optical emission spectroscopy. The emitted
      intensities of 388, 501, 587, and 667 nm lines were measured side-on and end-on
      with respect to the discharge axis. The comparison of optically thin side-on
      spectra with end-on spectra, which exhibited the absorption effects in the line
      kernels, enabled the determination of the average values of the number densities
      n1 in the considered He states along the plasma length L. The field of the
      theoretical profiles for a series of the n1L parameters pertinent to the
      experimental conditions was calculated for each line. By introducing the
      experimental data into the field of calculated curves, n1L corresponding to the
      particular state could be obtained. The measurements of the emission profiles
      were done as a function of the discharge voltage in the range covering
      homogeneous as well as filamentary DBD operation mode. Due to nonuniformity of
      the excited atom density distribution along the plasma, the values of n1 could be
      obtained only in the homogeneous operation mode where the nonuniformity was
      small. The following maximum values were found for the number densities in the
      investigated states: n1 av (2s 3S1) = (2.9 +/- 1.1) * 1013 cm-3, n1 av (2s 1S) =
      (1.4 +/- 0.5) * 1013 cm-3, n1 av (2p 3P0 J) = (1.1 +/- 0.4) * 1013 cm-3, n1 av
      (2p 1P0) = (4.2 +/- 1.6) * 1012 cm-3, and they represent the average populations
      along the plasma column in the capillary.

PMID- 24320178
TI  - Helix-loop-helix protein Id2 stabilizes mammalian circadian oscillation under
      constant light conditions.
AB  - The mammalian circadian oscillator is composed of interacting positive and
      negative transcription events. The clock proteins PER1 and PER2 play essential
      roles in a negative limb of the feedback loop that generates the circadian rhythm
      in mammals. In addition, the proteins CLOCK and BMAL1 (also known as ARNTL) form
      a heterodimer that drives the Per genes via the E-box consensus sequences within
      their promoter regions. In the present study, we demonstrate that Id2 is involved
      in stabilization of the amplitudes of the circadian oscillations by suppressing
      transcriptional activation of clock genes Clock and Bmal1. Id2 shows dynamic
      oscillation in the SCN, with a peak in the late subjective night. Under constant
      dark conditions (DD), Id2(-/-) mice showed no apparent difference in locomotor
      activity, however, under constant light conditions (LL), Id2(-/-) mice exhibit
      aberrant locomotor activity, with lower circadian oscillation amplitudes,
      although the free running periods in Id2(-/-) mice show no differences from those
      in either wild type or heterozygous mice. Id2(-/-) animals also exhibit
      upregulation of Per1 in constant light, during both the subjective night and day.
      In wild type mice, Id2 is upregulated by constant light exposure during the
      subjective night. We propose that Id2 expression in the SCN contributes to
      maintenance of dynamic circadian oscillations. 

PMID- 24320176
TI  - Prospective registry of symptomatic severe aortic stenosis in octogenarians: a
      need for intervention.
AB  - OBJECTIVE: To study the factors associated with choice of therapy and prognosis
      in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN:
      Prospective, observational, multicenter registry. Centralized follow-up included
      survival status and, if possible, mode of death and Katz index. SETTING:
      Transnational registry in Spain. SUBJECTS: We included 928 patients aged >=80
      years with severe symptomatic AS. INTERVENTIONS: Aortic-valve replacement (AVR),
      transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN
      OUTCOME MEASURES: All-cause death. RESULTS: Mean age was 84.2 +/- 3.5 years, and
      only 49.0% were independent (Katz index A). The most frequent planned management
      was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and
      AVR in 244 (26%). The main reason against recommending AVR in 684 patients was
      high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient
      refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35
      (5.1%)]. The mean time from treatment decision to AVR was 4.8 +/- 4.6 months and
      to TAVI 2.1 +/- 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357
      patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%,
      72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple
      propensity score, was associated with lower mortality when compared with planned
      conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI]
      0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION:
      Octogenarians with symptomatic severe AS are frequently managed conservatively.
      Planned conservative management is associated with a poor prognosis.

PMID- 24320179
TI  - Sex differences in stress reactivity of hippocampal BDNF in mice are associated
      with the female preponderance of decreased locomotor activity in response to
      restraint stress.
AB  - The incidence and prevalence of depression is higher in women than in men, but
      the cause of this sex discrepancy remains unknown. Brain-derived neurotrophic
      factor (BDNF) is a key protein for maintaining neuronal integrity. The purpose of
      this study was to investigate the female preponderance in behavioral responsivity
      to restraint stress focusing on the stress reactivity of BDNF in the hippocampus.
      Male and female ICR mice were exposed to a 3-h session of restraint stress.
      Plasma corticosterone was measured by high-performance liquid chromatography.
      BDNF mRNA expression in the whole hippocampus was measured by quantitative real
      time reverse transcription-polymerase chain reaction. Wheel-running activity was
      monitored during the dark period. In response to restraint stress, the increase
      in levels of serum corticosterone was higher in female than in male mice.
      Restraint stress resulted in decreased voluntary wheel-running behavior that was
      greater in female than male animals. In addition to these sex differences in
      stress reactivity, we found a significant sex difference in BDNF levels in the
      hippocampus of restraint-stressed mice; total BDNF levels significantly decreased
      in female mice, but not in male mice in response to the stress. Furthermore, BDNF
      exon I and IV mRNA expression also showed the same tendency. These data indicate
      that the reduction in levels of voluntary wheel-running activity in response to
      stress can be significantly influenced by sex. Moreover, our findings suggest a
      link between the sex differences in this behavioral response to stress and
      differential stress reactivity in the production of BDNF in the hippocampus. 

PMID- 24320180
TI  - Rutting vocalizations of Formosan sika deer Cervus nippon taiouanus-acoustic
      structure, seasonal and diurnal variations, and individuality.
AB  - In sika deer Cervus nippon, rutting vocalizations play an important role in
      breeding behavior. This study investigated two types of rutting vocalizations,
      the moan and the howl, of the Formosan sika deer C. n. taiouanus, including the
      acoustic characteristics of the vocalizations, the diurnal and seasonal
      variations of vocal activity, and individual acoustic variation and
      identification. The results showed that the sound levels were approximately 81-88
      dB(A) for the moan and 92-96 dB(A) for the howl, at a distance of 7 m from the
      sources. From October 2006 to January 2007, eight days of continuous observations
      were conducted to record the type and amount of vocalizations. Both moan and howl
      began to occur in the middle of October and reached peaks in the middle and end
      of November. Thereafter, few vocalizations were recorded until mid-January 2007.
      Moreover, we found that 74.5% of the first portion of moan, 65.3% of the second
      portion of moan, and 64.2% of howl could be identified on an individual basis by
      using discriminant analysis with 200 iterations of cross-validation test. These
      results revealed that the sounds differed among individuals, and also that they
      could be correctly identified. Our findings add to the scientific knowledge of
      sika deer behavior and provide the basis for a novel method of monitoring sika
      deer populations. 

PMID- 24320181
TI  - Evaluation of canine bone marrow-derived mesenchymal stem cells after long-term
      cryopreservation.
AB  - Autologous bone marrow-derived mesenchymal stem cell (BMSCs)-based therapies show
      great potential in regenerative medicine. However, long-term storage and
      preservation of BMSCs for clinical use is still a great clinical challenge. The
      present study aimed to analyze the effect of long-term cryopreservation on the
      regenerative ability of BMSCs. After cryopreservation of BMSCs from beagle dogs
      for three years, cell viability, and quantitative analysis of alkaline
      phosphatase (ALP) activity, surface adherence, and mineralized nodule formation
      were analyzed. BMSCs in cell-scaffold complex were then implanted into nude mice.
      There was no significant difference in cell viability and ALP activity between
      osteogenic differentiation and non-osteogenic differentiation of BMSCs, and BMSCs
      in cell-scaffold complex retained osteogenic differentiation ability in vivo.
      These results indicate that long-term cryopreserved BMSCs maintain their have
      capacity to contribute to regeneration. 

PMID- 24320182
TI  - In vitro thermal effects on embryonic cells of endangered hawksbill turtle
      Eretmochelys imbricata.
AB  - The hawksbill turtle is an ectotherm, whose sex is determined by temperature
      during embryonic development. This study aimed to determine whether embryonic
      hawksbill turtle cells respond differently to temperature than mammalian cells.
      Embryonic hawksbill turtle cells were established in culture, and thermal effects
      on these cells were investigated in vitro. Cells were maintained in Dulbecco's
      Modified Eagle Medium supplemented with non-essential amino acids, vitamin
      solution, sodium pyruvate, and 10% fetal bovine serum at 33 degrees C and cell
      proliferation occurred at 25-33 degrees C. When cells were incubated at 37
      degrees C (the temperature of mammalian cell culture) for 24 h, cell growth was
      completely inhibited. This growth inhibition was evidently recovered by changing
      the incubation temperature back to 33 degrees C. Expression of heat shock protein
      was found to increase with elevating culture temperature from 25 to 33 degrees C.

PMID- 24320184
TI  - Courtship patterns in the Drosophila montium species subgroup: repeated loss of
      precopulatory courtship?
AB  - During precopulatory courtship, male Drosophila typically produce wing vibration
      to generate species-specific songs before mounting females. Three species in the
      lini clade of the montium species subgroup have been found to produce species
      specific sine song only after mounting and during copulation. Here we
      investigated and analyzed the courtship behavior of 29 species in the montium
      subgroup from video and song recordings and measured the duration of wing
      vibration. We describe a great diversity of courtship behavior in the montium
      subgroup. The courtship patterns can be categorized into four types in the
      montium subgroup: 1) type P/C, species with both precopulatory and copulatory
      courtship, such as D. parvula and D. nikananu, 2) type P-/C, species with
      sporadic precopulatory and mainly copulatory courtship, such as D. auraria and D.
      triauraria. 3) type C, species with only copulatory courtship, such as D. tani
      and D. pectinifera, 4) type C-, species with only very brief copulatory
      courtship, such as D. rufa and D. asahinai. According to a phylogenetic tree
      based on sequences of mitochondrial COI and COII, and the nuclear Adh, both
      precopulatory courtship and copulatory courtship were present in the most basal
      species D. parvula. Each of two branches in the montium subgroup contains four
      types of courtship behavior. Type C is present in each sub-branch. These results
      suggest that the courtship behavior initially involved both precopulatory and
      copulatory courtship, but that subsequently precopulatory courtship has gradually
      been lost in the montium subgroup. We suggest reasons why precopulatory behavior
      might come to be lost in the montium subgroup. 

PMID- 24320183
TI  - Molecular cloning and gene expression of mummichog (Fundulus heteroclitus) Runx2
      during embryogenesis.
AB  - In our previous study, we clarified the toxicity of 2,2'-dipyridyldisulfide
      [(PS)2], one of photodegradation products of a metal pyrithione that is used as
      an alternative antifouling paint biocides to organotin compounds in Japan. In
      early life stage toxicity tests, we exposed the mummichog, (Fundulus
      heteroclitus) to (PS)2, and the hatched larvae subsequently displayed notochord
      undulations and skeletal deformities ( Mochida et al., 2012 ). Runx2, a
      transcription factor of the runt family, is a key regulator in skeletal
      development in mammals. It is possible that (PS)2 inhibits Runx2 gene expression,
      inducing the skeletal deformities in mummichog. In the present study, we cloned
      two Runx2 cDNAs (type I and type II) from mummichog embryos. The deduced amino
      acid sequences of type I and type II contain an open reading frame encoding 450
      and 464 amino acid residues, respectively. The derived amino acid sequence of
      Fundulus Runx2 type I showed the highest identity (93.8%) with Takifugu Runx2
      type I, and Fundulus Runx2 type II showed 94.6% homology with medaka Runx2. The
      expression level of Runx2 mRNA in the early stage series was measured using a
      real-time quantitative PCR assay. Expression levels tended to increase in both
      the blastula-gastrula and the retinal pigmentation stage. To examine the effect
      of toxic compounds on skeletal formation, mummichog embryos in the late blastula
      to retinal pigmentation stage were exposed to (PS)2. After exposure to (PS)2 for
      one week, the expression level of Runx2 mRNA was unchanged. These results suggest
      that there is no inhibition of Runx2 gene expression due to (PS)2 exposure. 

PMID- 24320185
TI  - How far from water? terrestrial dispersal and nesting sites of the freshwater
      turtle Phrynops hilarii in the floodplain of the Parana River (Argentina).
AB  - Terrestrial environments surrounding aquatic resources are important and
      intensively used by semi-aquatic species. In the present work, terrestrial
      dispersal and nesting sites of the freshwater turtle Phrynops hilarii were
      analyzed in the floodplain of the Parana River, using field data and variables
      obtained from remote sensing. A total of 112 turtles and 44 nests were recorded
      during road sampling for one year (covered a total of 786 km in 30 surveys).
      Individuals were at a mean distance of 171.45 m from water, with a negative
      correlation between number of turtles and distance from water bodies. No
      significant differences in distance of turtles from water were observed among
      seasons. Phrynops hilarii nested at a mean distance of 136.51 m from water,
      showing a negative correlation between number of nests and distance from water
      bodies. Mean elevation of nests relative to maximum level of water body nearest
      each record was 1.13 m. The correlation between number of nests and elevation of
      the nearest water body was positive and significant. The landscape surrounding
      wetlands is important for P. hilarii to complete the life cycle, as nesting is
      done in this environment. Our results show that the habitat selected for nesting
      and terrestrial dispersal was proportionally different from that available in the
      entire study area, with a higher proportion of wetlands, grasslands and forests. 

PMID- 24320186
TI  - Annual changes in fecal sex hormones with corresponding changes in reproductive
      behaviors in Thai sarus crane, black-headed Ibis, and Lesser Adjutant Stork.
AB  - We monitored annual fecal sex hormones and reproductive displays of five
      individuals of males and females Thai sarus crane (Grus antigone sharpii), a
      flock of five males and females black-headed Ibis (Threskiornis melanocephalus),
      and five pair bonded lesser adjutant stork (Leptoptilos javanicus), all
      maintained in captivity at Bangprha Waterbird Breeding Research Center.
      Reproductive behaviors were observed during 0600-1800 h, for four days during the
      second week of each month and feces were collected monthly to determine annual
      male total testosterone (mTT) and female estradiol (fE2) levels by
      radioimmunoassay. Thai sarus crane exhibited a peak mTT in August following a
      fE2, with a surge in July. Black-headed ibis demonstrated a peak mTT in January
      prior to a fE2 with a surge in March. Lesser adjutant stork showed a maximal mTT
      coincidently with fE2 with a surge in October. Thai sarus crane frequently
      displayed courtship in May-October, corresponding well with higher mTT rather
      than fE2 levels. Black-headed ibis showed courtship-copulation displays in
      January, simultaneously with mTT, but not with fE2 surge. Lesser adjutant stork
      often displayed courtship-copulation in October-January, seemingly corresponded
      with higher mTT and fE2 levels during October-December and October-November,
      respectively. Male and female lesser adjutant stork displayed egg-incubation and
      chick-rearing behaviors in November-January and December-June, respectively. We
      suggest that mTT and/or fE2 apparently played an important role in regulation of
      courtship-copulation displays but did not relate to both egg-incubation and
      chickrearing behaviors. 

PMID- 24320187
TI  - Identification and distribution of three gonadotropin-releasing hormone (GnRH)
      isoforms in the brain of a clupeiform fish, Engraulis japonicus.
AB  - To gain a better understanding of the reproductive endocrinology of a primitive
      order clupeiform fish (Japanese anchovy, Engraulis japonicus), cDNAs encoding
      three gonadotropin-releasing hormone (GnRH) isoforms were isolated from the
      brain, and their distribution was analyzed using insitu hybridization (ISH). The
      three GnRH isoforms include GnRH1 (herring GnRH), GnRH2 (chicken GnRH-ll) and
      GnRH3 (salmon GnRH), and their full-length cDNAs encode 88, 86, and 89 deduced
      amino acids (aa), respectively. Alignment analysis of Japanese anchovy GnRH
      isoforms showed lower identities with other teleost fish. The major population of
      GnRH1 neurons was localized in the ventral telencephalon (VT) and nucleus
      preopticus (NPO) of the preoptic area (POA) with minor population in the anterior
      olfactory bulb (OB). GnRH2 neurons were restricted to the midbrain tegmentum
      (MT), specific to the nucleus of the medial longitudinal fasciculus (nMLF). GnRH3
      neurons were localized in the olfactory nerve (ON), ventral OB, and transitional
      area between OB and ON. Interestingly, GnRH1 neurons were also localized in the
      olfactory bulb, in addition to its major population in the preoptic area. These
      results indicate the differential distribution of three GnRH isoforms expressed
      in the brain of the Japanese anchovy. 

PMID- 24320188
TI  - Loss of genetic diversity at an MHC locus in the endangered Tokyo bitterling
      Tanakia tanago (Teleostei: Cyprinidae).
AB  - Genetic diversity at a major histocompatibility complex (MHC) class II B gene was
      examined for two wild and three captive populations of the endangered Tokyo
      bitterling Tanakia tanago. A specific primer set was first developed to amplify
      the MHC II B exon 2 locus. Using single strand conformation polymorphism (SSCP)
      and sequencing analysis, 16 DAB3 alleles were detected with 56 nucleotide
      substitutions in the 276-bp region. In the putative antigen-binding sites of exon
      2, the rate of nonsynonymous substitutions was significantly higher than that of
      synonymous substitutions (dN/dS = 2.79), indicating positive selection on the
      retention of polymorphism. The population from the Handa Natural Habitat
      Conservation Area and that from the Tone River system exhibited low variation
      (one and three alleles, respectively), whereas the captive population that
      originated from a mix of three distinct populations had the highest amounts of
      variation (14 alleles). The levels of heterozygosity at the MHC varied
      considerably among populations and showed significant correlations with those at
      putative neutral microsatellite markers, suggesting that genetic drift following
      a bottleneck has affected MHC variability in some populations. Comparisons
      between endangered and non-endangered fish species in previous reports and the
      present results indicate that the number of MHC alleles per population is on
      average 70% lower in endangered species than non-endangered species. Considering
      the functional consequence of this locus, attention should be paid to captive and
      wild endangered fish populations in terms of further loss of MHC alleles. 

PMID- 24320189
TI  - Whole egg and alevin changes of cortisol and interrenal tissue differences in
      rainbow trout Oncorhynchus mykiss exposed to different stocking densities during
      early development.
AB  - Cortisol level changes in response to stocking density in the early stages of
      rainbow trout were measured. Eggs were exposed to low, normal, and high (2.55,
      5.10 and 7.65 eggs cm(-2)) densities during the incubation period. Cortisol of
      maternal origin was found in pre-fertilized eggs (5.09 +/- 0.12 ng g(-1)) of
      rainbow trout. In newly fertilized eggs, resting Cortisol levels (3.68 +/- 0.14
      ng g(-1)) decreased to 0.58 +/- 0.08, 0.60 +/- 0.12, and 0.57 +/- 0.16 ng g(-1)
      at low, normal and high densities by day 10 (organo-genesis), respectively.
      Resting Cortisol levels remained constant until the eyed stage (day 18). Then,
      Cortisol showed an increase at hatching to 1.16 +/- 0.11, 1.20 +/- 0.12, and 1.21
      +/- 0.14 ng g(-1) at low, normal, and high densities, respectively. The pattern
      of change in Cortisol level was similar in all three densities. Interrenal cells
      were observed in 1-day old alevins at all three densities. Hematopoietic tissue,
      renal tubules and nucleated red blood cells were clarified through the head part
      of kidney. Higher numbers and larger interrenal cells were observed at high
      density groups. Chronic density stress test conducted on embryonic stages of
      rainbow trout revealed no differences in Cortisol levels, but had an effect on
      the abundance and size of the interrenal cells. Densities were equaled after
      hatching (200 alevins per replicate) to investigate the different densities of
      eggs on stress indices in rainbow trout alevins. An acute stress (air exposure of
      eggs for five minutes) was applied in three treatments two weeks after hatching,
      and samples were taken at 0, 1, 3, 6, and 24 hps (hours post stress). Cortisol
      content increased under low density in 1 hps and reached from 5.21 +/- 0.13 ng g(
      1) to 6.01 +/- 0.18 ng g(-1) (P < 0.05). Cortisol levels increased under normal
      density in 1 hps from 6.03 +/- 0.28 ng g(-1) to 10.84 +/- 0.18 ng g(-1) (P <
      0.05). In high density also Cortisol increased from 6.83 +/- 0.23 ng g(-1) to
      8.86 +/- 0.26 ng g(-1) (P < 0.05). At 3 hps;, Cortisol level was returned to
      basal level under low (P > 0.05) and normal (P > 0.05) densities, but
      significantly decreased (P < 0.05) under high density. Results revealed that the
      Cortisol biosynthesis was observed in rainbow trout between eyeing to the
      hatching stage. An increase in the density of eggs until 7.65 egg cm(-2) impaired
      Cortisol secretion and feedback system in alevins. However, more studies are
      needed to identify the exact time for Cortisol synthesis ability from eyeing to
      hatching in this species. 

PMID- 24320190
TI  - Capacitation and acrosome reaction induction on thawed Dama dama deer
      spermatozoa: glycine effect as cryopreservation diluent supplement.
AB  - The aim of this research was to evaluate two different diluents for sperm
      cryopreservation and to study functional parameters in relation to the response
      to heparin, lysophosphatidylcholine and progesterone, in frozen-thawed semen of
      fallow deer (Dama dama) during the reproductive season (brama). In this way,
      fallow deer can be used as a biological model of endangered cervids. Semen was
      obtained by electroejaculation. Heparin, progesterone and lysophosphatidylcholine
      were used as capacitation and acrosome reaction inducers, respectively.
      Capacitation and acrosome reaction were evaluated by chlorotetracycline
      epifluorescence technique (CTC), membrane integrity by Hypo-osmotic swelling test
      (HOS) and viability and acrosome integrity by trypan blue stain/DIC. Data was
      analyzed by ANOVA and Tukey Test (P < 0.05). Semen was cryopreserved in different
      diluents and Fructose-Tris-Glycine extender was selected. Capacitation with
      heparin at different incubation times determined that the highest capacitation
      percentage was obtained at 45 minutes incubation. Progesterone (1 'M) and
      lysophosphatidylcholine in heparin capacitated sperm induced acrosome reaction (P
      < 0.05). This study contributes to improve cryopreservation methods and to
      increase the knowledge about capacitation and acrosome reaction in vitro in deer
      spermatozoa, allowing an advance in the development of reproductive
      biotechnologies. 

PMID- 24320191
TI  - Synthesis of spiroaminals and spiroketals with bimetallic relay catalysis.
AB  - A novel tandem metal relay catalytic system was developed by combining gold
      catalyzed cycloisomerization with an early transition-metal-catalyzed inverse
      electron-demand hetero-Diels-Alder (IED-HDA) reaction. Various biologically
      important spiroaminals and spiroketals were obtained with very high efficiency
      under mild conditions. 

PMID- 24320192
TI  - Viability and adaptation potential of indigenous microorganisms from natural gas
      field fluids in high pressure incubations with supercritical CO2.
AB  - Carbon Capture and Storage (CCS) is currently under debate as large-scale
      solution to globally reduce emissions of the greenhouse gas CO2. Depleted gas or
      oil reservoirs and saline aquifers are considered as suitable reservoirs
      providing sufficient storage capacity. We investigated the influence of high CO2
      concentrations on the indigenous bacterial population in the saline formation
      fluids of a natural gas field. Bacterial community changes were closely examined
      at elevated CO2 concentrations under near in situ pressures and temperatures.
      Conditions in the high pressure reactor systems simulated reservoir fluids i)
      close to the CO2 injection point, i.e. saturated with CO2, and ii) at the outer
      boundaries of the CO2 dissolution gradient. During the incubations with CO2,
      total cell numbers remained relatively stable, but no microbial sulfate reduction
      activity was detected. After CO2 release and subsequent transfer of the fluids,
      an actively sulfate-respiring community was re-established. The predominance of
      spore-forming Clostridiales provided evidence for the resilience of this taxon
      against the bactericidal effects of supercritical (sc)CO2. To ensure the long
      term safety and injectivity, the viability of fermentative and sulfate-reducing
      bacteria has to be considered in the selection, design, and operation of CCS
      sites. 

PMID- 24320193
TI  - Shared care combined with telecare improves glycemic control of diabetic patients
      in a rural underserved community.
AB  - OBJECTIVE: To investigate the effectiveness of shared care combined with telecare
      in type 2 diabetic patients in an underserved community in Asia. RESEARCH DESIGN
      AND METHODS: In total, 95 patients with type 2 diabetes who had a glycosylated
      hemoglobin (HbA1c) level of >7% were recruited from six community health centers
      in remote areas in Changhua County, Taiwan. All patients were randomly divided
      into intervention (shared care combined with telecare) and usual-care groups and
      followed up for 6 months. RESULTS: The decrease in HbA1c level was significantly
      greater in the intervention group than in the usual-care group (0.7 +/- 1.3%
      versus 0.1 +/- 1.0%, p=0.03). There were no significant differences in lipid
      profiles and blood pressure changes between the two groups. CONCLUSIONS: Shared
      care combined with telecare could significantly reduce HbA1c levels in type 2
      diabetic patients with poor glycemic control in underserved rural communities.
      Further studies should be conducted to clarify the target users and to develop
      cost-effective interventions.

PMID- 24320194
TI  - Development and evaluation of a self-regulating alternating pressure air cushion.
AB  - PURPOSE: To investigate the effect of alternating air cells of a newly developed
      dynamic cushion on interface pressure and tissue oxygenation levels. METHOD: This
      cross-over experimental study included 19 healthy volunteers. The dynamic cushion
      used has an automatic self-regulating alternating pressure air-cell system with
      35 small and four large air cells for maintaining posture while seated. This
      cushion also has 17 bottoming-out detectors that automatically inflate the air
      cells to release a high interface pressure. To assess the effect of this
      alternating system, participants sat on the new cushion with an alternating
      system or static system for 30 min and then performed push-ups. The interface
      pressure was monitored by pressure-sensitive and conductive ink film sensors and
      tissue oxygenation levels were monitored by near-infrared spectroscopy. A
      reactive hyperaemia indicator was calculated using tissue oxygenation levels as
      an outcome measure. RESULTS: The peak interface pressure was not significantly
      different between the groups. The reactive hyperaemia indicator was significantly
      higher in the static group than in the alternating group. CONCLUSIONS: An
      alternating system has beneficial effects on blood oxygenation levels without
      increasing interface pressure. Therefore, our new cushion is promising for
      preventing pressure ulcers with patients with limited ability to perform push
      ups. Implications for Rehabilitation A dynamic cushion was developed, which
      consists of a uniquely-designed air-cell layout, detectors for bottoming out, and
      an alternating system with multiple air-cell lines. The alternating system did
      not increase interface pressure and it significantly reduced reactive hyperaemia
      after 30 min of sitting in healthy volunteers. This cushion is a new option for
      individuals who require stable posture but have limitations in performing
      scheduled push-ups for prevention of pressure ulcers.

PMID- 24320195
TI  - Review on design and control aspects of ankle rehabilitation robots.
AB  - Ankle rehabilitation robots can play an important role in improving outcomes of
      the rehabilitation treatment by assisting therapists and patients in number of
      ways. Consequently, few robot designs have been proposed by researchers which
      fall under either of the two categories, namely, wearable robots or platform
      based robots. This paper presents a review of both kinds of ankle robots along
      with a brief analysis of their design, actuation and control approaches. While
      reviewing these designs it was observed that most of them are undesirably
      inspired by industrial robot designs. Taking note of the design concerns of
      current ankle robots, few improvements in the ankle robot designs have also been
      suggested. Conventional position control or force control approaches, being used
      in the existing ankle robots, have been reviewed. Apparently, opportunities of
      improvement also exist in the actuation as well as control of ankle robots.
      Subsequently, a discussion on most recent research in the development of novel
      actuators and advanced controllers based on appropriate physical and cognitive
      human-robot interaction has also been included in this review. Implications for
      Rehabilitation Ankle joint functions are restricted/impaired as a consequence of
      stroke or injury during sports or otherwise. Robots can help in reinstating
      functions faster and can also work as tool for recording rehabilitation data
      useful for further analysis. Evolution of ankle robots with respect to their
      design and control aspects has been discussed in the present paper and a novel
      design with futuristic control approach has been proposed.

PMID- 24320196
TI  - Dermoscopic patterns of cutaneous melanoma metastases.
AB  - In 2-8% of patients with melanoma, the first clinical manifestation of the
      disease may be skin metastasis. In these cases, differential diagnosis with the
      primary melanoma, benign melanocytic lesions, and other malignant and benign skin
      growths is particularly challenging. For this reason, the dermatologist's
      approach to cutaneous metastases of malignant melanoma calls for knowledge of the
      great morphological variety of these lesions. Dermoscopic characteristics
      associated with CMMMs have not yet been codified. The aim of the present review
      is to provide additional information about dermoscopic aspects of these skin
      lesions. 

PMID- 24320197
TI  - Acquired dyskeratotic leukoplakia of the lip and conjunctiva.

PMID- 24320198
TI  - Oral infestation with leech Limnatis nilotica in two mixed-breed dogs.
AB  - Leeches are bloodsucking hermaphroditic parasites that attach to tissues using
      two muscular suckers, ingest large amounts of blood and may cause severe anaemia
      in the host. Two four-month-old mixed-breed dogs (one bitch and one male) were
      referred with anorexia, retching, hypersalivation and bleeding from the oral
      cavity. On physical examination, two live leeches were detected on the ventral
      aspect of the tongue of the bitch and one in a similar position in the male. The
      leeches were gently detached and removed using Adson tissue forceps after
      applying vinegar over the area. Microcytic hypochromic anaemia was detected in
      the bitch and mild leukocytosis in the dog. One month after treatment both
      animals were re-examined and a complete blood count was normal. Given that
      infestation with leeches as described here is associated with contaminated water,
      the use of clean and safe drinking water is recommended to avoid such diseases. 

PMID- 24320201
TI  - Outcome of patients with microscopic and macroscopic metastatic nodal Merkel cell
      carcinoma: an Australian experience.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy
      with a high rate of nodal metastasis. The American Joint Committee on Cancer
      staging system subclassifies nodal disease into microscopic and macroscopic
      groups based on prognosis. OBJECTIVE: To compare the outcome of patients with
      microscopic and macroscopic nodal metastases. MATERIALS AND METHODS: Patients
      were identified from a database of 180 patients with MCC who presented to
      Westmead Hospital, Sydney, Australia, from 1980 to 2013. Disease-free survival
      (DFS), overall survival (OS), and follow-up were calculated using Kaplan-Meier
      curves and compared using the log-rank (Mantel-Cox) test. RESULTS: Forty-one
      patients were diagnosed with node-positive MCC; 11 patients had microscopic nodal
      metastases, with five (45%) relapsing, and 30 had macroscopic disease, with 17
      (57%) relapsing. There was no significant difference in DFS (p = .93) or OS (p =
      .63) between the two groups. CONCLUSION: The nonsignificant difference in DFS and
      OS suggest that even microscopic nodal metastases can predict a poor outcome.
      Because more than half of patients subsequently relapse, often at a distant site,
      there is a need to develop an effective systemic treatment.

PMID- 24320199
TI  - Amblyomma cajennense (Fabricius, 1787) (Acari: Ixodidae), the Cayenne tick:
      phylogeography and evidence for allopatric speciation.
AB  - BACKGROUND: Amblyomma cajennense F. is one of the best known and studied ticks in
      the New World because of its very wide distribution, its economical importance as
      pest of domestic ungulates, and its association with a variety of animal and
      human pathogens. Recent observations, however, have challenged the taxonomic
      status of this tick and indicated that intraspecific cryptic speciation might be
      occurring. In the present study, we investigate the evolutionary and demographic
      history of this tick and examine its genetic structure based on the analyses of
      three mitochondrial (12SrDNA, d-loop, and COII) and one nuclear (ITS2) genes.
      Because A. cajennense is characterized by a typical trans-Amazonian distribution,
      lineage divergence dating is also performed to establish whether genetic
      diversity can be linked to dated vicariant events which shaped the topology of
      the Neotropics. RESULTS: Total evidence analyses of the concatenated mtDNA and
      nuclear + mtDNA datasets resulted in well-resolved and fully congruent
      reconstructions of the relationships within A. cajennense. The phylogenetic
      analyses consistently found A. cajennense to be monophyletic and to be separated
      into six genetic units defined by mutually exclusive haplotype compositions and
      habitat associations. Also, genetic divergence values showed that these lineages
      are as distinct from each other as recognized separate species of the same genus.
      The six clades are deeply split and node dating indicates that they started
      diverging in the middle-late Miocene. CONCLUSIONS: Behavioral differences and the
      results of laboratory cross-breeding experiments had already indicated that A.
      cajennense might be a complex of distinct taxonomic units. The combined and
      congruent mitochondrial and nuclear genetic evidence from this study reveals that
      A. cajennense is an assembly of six distinct species which have evolved
      separately from each other since at least 13.2 million years ago (Mya) in the
      earliest and 3.3 Mya in the latest lineages. The temporal and spatial
      diversification modes of the six lineages overlap the phylogeographical history
      of other organisms with similar extant trans-Amazonian distributions and are
      consistent with the present prevailing hypothesis that Neotropical diversity
      often finds its origins in the Miocene, after the Andean uplift changed the
      topology and consequently the climate and ecology of the Neotropics.

PMID- 24320202
TI  - Do blood pressure levels and other patient characteristics influence native
      fistula patency?
AB  - Arteriovenous fistulas (AVFs) play an important role in access for hemodialysis,
      yet premature thrombosis is a challenge. This study identifies factors
      influencing primary patency in a series of AVF creations. Postoperative systolic
      blood pressure (BP) was of principal interest; demographical information,
      comorbidities, smoking status, warfarin, aspirin, clopidogrel, and statins were
      considered. A retrospective review of AVF creations performed by one surgeon
      between January 2008 and September 2010 was conducted. Fistula patency was
      denoted by a bruit and measured at 3 weeks and 12 months after surgery. One
      hundred and fifty-one AVF creations were studied; 134 fistulas (88.7%) were
      patent at 3 weeks and 85 (56.3%) at 12 months. The odds ratio (OR) for thrombosis
      at 12 months was 0.16 (95% CI: 0.04, 0.62; p = 0.008) among patients with a
      postoperative systolic BP of 120-139 mmHg compared with those with a BP of <= 119
      mmHg. Patients taking warfarin yielded an OR of 5.71 at 3 weeks (95% CI: 1.20,
      27.11; p = 0.028), and 3.33 at 12 months (95% CI: 1.01, 10.99; p = 0.048). No
      other variables were statistically significant. Patients with postoperative
      systolic BP of 120-139 mmHg showed a reduction in fistula thromboses compared
      with patients with a systolic BP of <= 119 mmHg. Patients on warfarin were less
      likely to maintain a patent fistula.

PMID- 24320203
TI  - Assessment of sublingual misoprostol as first-line treatment for primary post
      partum hemorrhage: results of a multicenter trial.
AB  - AIM: The study investigated the effectiveness of sublingual misoprostol when used
      as primary treatment of primary post-partum hemorrhage (PPH) in a low-income
      country. METHODS: Maternity care providers in three Nigerian hospitals
      administrated 800 MUm sublingual misoprostol to women experiencing PPH. The
      outcome variables were estimated blood loss and the need for additional
      uterotonic drugs after initial treatment with misoprostol. Entry criteria
      included women in term spontaneous labor, while exclusion criteria were women
      with operative delivery and those experiencing PPH not due to atonic uterus.
      RESULTS: One hundred and thirty-one women with PPH were treated over 6 months.
      Estimated blood loss ranged 500-2500 mL. Twenty women (15.3%) required additional
      uterotonic drugs to control continuing blood loss. There were no maternal deaths,
      while seven perinatal deaths were recorded. CONCLUSION: We conclude that although
      sublingual misoprostol is effective in reducing blood loss due to PPH, it does
      not effectively treat all forms of PPH. Additional uterotonics and other
      ancillary treatments would be required.

PMID- 24320204
TI  - Protective effect of an egg yolk-derived immunoglobulin (IgY) against Prevotella
      intermedia-mediated gingivitis.
AB  - AIMS: To investigate the effects of an egg yolk-derived immunoglobulin (IgY)
      specific to Prevotella intermedia in vitro and in vivo. METHODS AND RESULTS: An
      IgY specific to P. intermedia was produced by immunizing hens with formaldehyde
      inactivated P. intermedia and showed high titres when subjected to an ELISA. The
      obtained IgY inhibited the growth of P. intermedia in a dose-dependent manner at
      concentrations from 1 to 20 mg ml(-1) in Center for Disease Control and
      Prevention liquid medium. Forty rats were challenged with P. intermedia on
      gingivae and then randomly divided into four groups, which were syringed
      respectively with phosphate-buffered saline, 1 mg ml(-1) of tinidazole, 20 mg ml(
      1) of nonspecific IgY and 20 mg ml(-1) of the IgY specific to P. intermedia at a
      dosage of 300 MUl per day. Gingival index (GI), plaque index (PI), bleeding on
      probing (BOP), counts of white blood cell (WBC) and histopathological slide of
      the gums were measured after treatment for 15 days. The gingivitis rats treated
      with the IgY specific to P. intermedia showed significantly decreased GI, PI, BOP
      and WBC (P < 0.05). Gum histopathology of the treated rats demonstrated a
      superior protective effect of the specific IgY on P. intermedia-mediated
      gingivitis. CONCLUSIONS: A new immunoglobulin specific to P. intermedia was
      developed from egg yolk. This specific IgY can dose-dependently inhibit the
      growth of P. intermedia and protect rats from gingivitis induced by P.
      intermedia. SIGNIFICANCE AND IMPACT OF THE STUDY: The new IgY has potential for
      the treatment of P. intermedia-mediated gingivitis.

PMID- 24320205
TI  - Socio-spatial patterning of off-sale and on-sale alcohol outlets in a Texas city.
AB  - INTRODUCTION AND AIMS: To examine the socio-spatial patterning of off-sale and on
      sale alcohol outlets following a policy change that ended prohibition of off-sale
      outlets in Lubbock, Texas. DESIGN AND METHODS: The spatial patterning of alcohol
      outlets by licensing type was examined using the k-function difference (D
      statistic) to compare the relative degree of spatial aggregation of the two types
      of alcohol outlets and by the spatial scan statistic to identify statistically
      significant geographic clusters of outlets. The sociodemographic characteristics
      of the areas containing clusters of outlets were compared with the rest of the
      city. In addition, the socioeconomic characteristics of census block groups with
      and without existing on-sale outlets were compared, as were the socioeconomic
      characteristics of census block groups with and without the newly issued off-sale
      licenses. RESULTS: The existing on-sale premises in Lubbock and the newly
      established off-sale premises introduced as a result of the 2009 policy change
      displayed different spatial patterns, with the latter being more spatially
      dispersed. A large cluster of on-sale outlets identified in the north-east of the
      city was located in a socially and economically disadvantaged area of the city.
      DISCUSSION AND CONCLUSION: The findings support the view that it is important to
      understand the local context of deprivation within a city when examining the
      location of alcohol outlets and add to the existing research by drawing attention
      to the importance of geographic scale in assessing such relationships.

PMID- 24320206
TI  - Bidirectional barbed suture in laparoscopic myomectomy: clinical features.
AB  - OBJECTIVE: To compare bidirectional knotless barbed suture versus standard
      sutures, with either extracorporeal or intracorporeal knots, and to assess the
      feasibility, safety, and rapidity in repairing a uterine wall defect after
      laparoscopic myomectomy. SUBJECTS AND METHODS: This was a randomized clinical
      study having a Canadian Task Force Classification of I. In tertiary-care
      university-based teaching hospitals, 117 women who underwent laparoscopic
      myomectomy were enrolled. In accord with randomization, uterine wall defects were
      closed with either extracorporeal (poliglecaprone 25; MonocrylTM-1; Ethicon Inc.,
      Somerville, NJ) or intracorporeal (polyglactin 910; VicrylTM-1; Ethicon Inc.)
      knots or a bidirectional knotless barbed suture (QuillTM-0; Angiotech
      Pharmaceuticals, Inc., Vancouver, BC, Canada). RESULTS: Time required to suture
      was significantly lower in the group operated on with a bidirectional suture than
      in groups with traditional sutures (P<.001). No significant difference was
      observed in operative time among the study groups. The degree of surgical
      difficulty was significantly lower in the Quill group than in the other groups.
      CONCLUSIONS: Use of barbed sutures reduces the time required to repair a uterine
      wall defect during laparoscopic myomectomy. In a follow-up of patients carried
      out at 3 months, 6 months, and 1 year after the surgery, there were no wound
      dehiscence, no bleeding, and no other potential major complications.

PMID- 24320208
TI  - Multiple, disparate redox pathways exhibited by a tris(pyrrolido)ethane iron
      complex.
AB  - Iron(III) complexes of the tris(pyrrolide)ethane trianion have been synthesized
      by reaction of one- and two-electron oxidants with [(tpe)Fe(THF)][Li(THF)4] (tpe
      = tris(5-mesitylpyrrolyl)ethane). X-ray crystallography, (57)Fe Mossbauer, (1)H
      NMR and EPR spectroscopy, SQUID magnetometry, and density functional theory
      calculations were employed to rigorously establish the iron 3+ oxidation state.
      All oxidants employed are proposed to operate via an inner-sphere electron
      transfer mechanism. Dialkyl peroxides and dibenzyldisulfide served to oxidize
      iron by one electron, and group transfer of an aryl nitrene unit to the Fe(2+)
      starting material resulted in formation of Fe(3+) amido species following H-atom
      abstraction by a presumed nitrenoid intermediate. Single electron transfer to and
      from diphenyldiazoalkane was also observed to yield a diphenyldiazomethanyl
      radical anion antiferromagnetically coupled to the S = 5/2 Fe(3+). Isolation of
      Fe(3+) complexes of tpe, in comparison with previous results wherein the tpe
      ligand was the redox active moiety, presents an unusual juxtaposition of two
      noncommunicating redox reservoirs, each accessible via different reaction
      pathways (namely, inner- and outer-sphere electron transfer). 

PMID- 24320209
TI  - Two novel anti-inflammatory 21-nordammarane saponins from tetraploid Jiaogulan (
      Gynostemma pentaphyllum ).
AB  - Two novel 20-oxo-21-nordammar-22, 24-diene saponins, 21-norgypenosides A (1) and
      B (2), were characterized from the aerial parts of tetraploid Jiaogulan (
      Gynostemma pentaphyllum ), a popular tea ingredient. Their structures, including
      the absolute configurations, were comprehensively elucidated by HRESIMS, 1D and
      2D NMR data, chemical degradation, and through comparison of the experimental and
      calculated electronic circular dichroism (ECD) spectra. The two compounds
      suppressed the expression of interleukin (IL)-1beta, cyclooxygenase (COX)-2, and
      tumor necrosis factor (TNF)-alpha mRNAs in the lipopolysaccharide-induced RAW
      264.7 mouse macrophage cells at 10 and 100 MUg/mL, suggesting their potential
      anti-inflammatory effects. 

PMID- 24320210
TI  - Accounting for population variation in targeted proteomics.
AB  - Individual proteomes typically differ from the reference human proteome at
      ~10,000 single amino acid variants. When viewed on the population scale, this
      individual variation results in a wide variety of protein sequences. In targeted
      proteomics experiments, such variability can confound accurate protein
      quantification. To assist researchers in identifying target peptides with high
      variability within the human population, we have created the Population Variation
      plug-in for Skyline, which provides easy access to the polymorphisms stored in
      dbSNP. Given a set of peptides, the tool reports minor allele frequency for
      common polymorphisms. We highlight the importance of considering genetic
      variation by applying the tool to public data sets.

PMID- 24320211
TI  - Provisional stimulus level corrections for low frequency bone-conduction ABR in
      babies under three months corrected age.
AB  - OBJECTIVE: To estimate bone-conduction stimulus level corrections by testing the
      auditory brainstem response (ABR) of normally-hearing newborns. The stimuli used
      were low frequency tone pips calibrated to reference levels derived from ISO 389
      values. DESIGN: Tone pips were presented via supra-aural earphones and a B71
      Radioear bone vibrator at 0.5 or 1 kHz. ABR thresholds from both transducers were
      compared at each frequency. STUDY SAMPLE: twenty-seven newborn hearing screening
      referrals (33 ears) who passed an ABR discharge criterion at 4 kHz. RESULTS:
      Median air- and bone-conduction ABR threshold differences were 30 dB at 0.5 kHz
      and 20 dB at 1 kHz. CONCLUSION: The 0.5 kHz data from this study and previous
      studies were compared. Previous studies suggested lower figures for the bone
      conduction stimulus level correction. Likely sources of this discrepancy are
      discussed. The average 0.5 kHz bone-conduction correction value for infants < 3
      months old is about 28 dB. The correction for 1 kHz is 20 dB. We recommend that
      calibration reference levels used in this study be adopted and that appropriate
      corrections be applied to bone conduction ABR thresholds in infants < 3 months
      old before calculation of any air-bone gap and subsequent clinical
      interpretation.

PMID- 24320212
TI  - Genetic association between NOD2 polymorphism and infection status by
      Mycobacterium avium ssp. paratuberculosis in German Holstein cattle.
AB  - The aim of the study was the analysis of the nucleotide-binding oligomerization
      domain containing 2 (NOD2, formerly CARD15) as a candidate gene for Mycobacterium
      avium ssp. paratuberculosis infection in cattle. Eleven SNPs in the NOD2 gene
      were identified, and finally, four SNPs were included in a case-control study
      using 324 German Holstein cows tested for paratuberculosis using fecal culture
      and ELISA. The SNP (GenBank) AY518738S04:g.521G>A in exon 4 showed a significant
      association between the fecal culture status of the animals and NOD2 allele
      variants. The other three SNPs showed no associations in German Holstein cows. 

PMID- 24320213
TI  - Design and syntheses of highly emissive aminobenzopyrano-xanthene dyes in the
      visible and far-red regions.
AB  - New derivatives of aminobenzopyrano-xanthene (ABPX) dyes have been designed and
      synthesized with high fluorescence quantum yields in the visible and far-red
      regions. It was kinetically demonstrated that the structurally rigid conjugation
      of the xanthene moiety, which is closely related to the reduction of the
      nonradiative deactivation process, is an effective molecular design for the
      drastic enhancement of fluorescence emission efficiency. 

PMID- 24320214
TI  - Erythema induratum of Bazin induced by tuberculin skin test.

PMID- 24320215
TI  - Allosteric regulation of epoxide opening cascades by a pair of epoxide hydrolases
      in monensin biosynthesis.
AB  - Multistep catalysis of epoxide hydrolase/cyclase in the epoxide opening cascade
      is an intriguing issue in polyether biosynthesis. A pair of structurally
      homologous epoxide hydrolases was found in gene clusters of ionophore polyethers.
      In the epoxide opening reactions with MonBI and MonBII involved in monensin
      biosynthesis, we found that MonBII and catalytically inactive MonBI mutant
      catalyzed two-step reactions of bisepoxide substrate analogue to afford bicyclic
      product although MonBII alone catalyzed only the first cyclization. The X-ray
      crystal structure of MonBI dimers suggested the importance of the KSD motif in
      MonBI/MonBI interaction, which was further supported by gel filtration
      chromatography of wild-type MonBI and mutant MonBI. The involvement of the KSD
      motif in heterodimer formation was confirmed by in vitro assay. Direct evidence
      of MonBI/MonBII interaction was obtained by native mass spectrometry. Its
      dissociation constant was determined as 2.21 * 10(-5) M by surface plasmon
      resonance. Our results suggested the involvement of an allosteric regulation
      mechanism by MonBI/MonBII interaction in monensin skeletal construction. 

PMID- 24320216
TI  - Angina bullosa hemorrhagica-like lesions: a rare presentation of drug-induced
      thrombocytopenia.

PMID- 24320217
TI  - Alkylperoxy radical photochemistry in organic aerosol formation processes.
AB  - Recent studies have shown that 254 nm light can be used to generate organic
      aerosol from iodoalkane/air mixtures via photodissociation of the C-I bond and
      subsequent oxidation of the alkyl radical. We examine organic aerosol formed from
      the 1-iodooctane photolysis at this wavelength using high-performance liquid
      chromatography (HPLC) with derivatization to selectively probe carbonyl- and
      hydroxyl-containing molecules. Tandem mass spectrometry reveals that the product
      distributions are much more complex than a traditional low-NOx peroxy-peroxy
      oxidation mechanism from a single parent isomer would justify. We propose that
      this difference is due to peroxy radical photochemistry, leading to two major
      channels: direct peroxy radical isomerization via internal H-abstraction and
      reverse dissociation to form alkyl radical and O2. The complexity of the product
      spectrum is derived from both scrambling of the radical site in the alkyl radical
      and the additional oxidation of otherwise stable peroxy radicals as a result of
      the isomerization. A branching ratio for these channels is estimated using a
      canonical representation of the internal energy distribution. Lifetime estimates
      using extrapolated ethyl peroxy absorption cross sections and the actinic flux
      near 310 nm show that peroxy radical photochemistry may play a role in defining
      the composition of atmospheric secondary organic aerosol formed in pristine (low
      NOx) environments. 

PMID- 24320218
TI  - Development of a model webserver for breed identification using microsatellite
      DNA marker.
AB  - BACKGROUND: Identification of true to breed type animal for conservation purpose
      is imperative. Breed dilution is one of the major problems in sustainability
      except cases of commercial crossbreeding under controlled condition. Breed
      descriptor has been developed to identify breed but such descriptors cover only
      "pure breed" or true to the breed type animals excluding undefined or admixture
      population. Moreover, in case of semen, ova, embryo and breed product, the breed
      cannot be identified due to lack of visible phenotypic descriptors. Advent of
      molecular markers like microsatellite and SNP have revolutionized breed
      identification from even small biological tissue or germplasm. Microsatellite DNA
      marker based breed assignments has been reported in various domestic animals.
      Such methods have limitations viz. non availability of allele data in public
      domain, thus each time all reference breed has to be genotyped which is neither
      logical nor economical. Even if such data is available but computational methods
      needs expertise of data analysis and interpretation. RESULTS: We found Bayesian
      Networks as best classifier with highest accuracy of 98.7% using 51850 reference
      allele data generated by 25 microsatellite loci on 22 goat breed population of
      India. The FST values in the study were seen to be low ranging from 0.051 to
      0.297 and overall genetic differentiation of 13.8%, suggesting more number of
      loci needed for higher accuracy. We report here world's first model webserver for
      breed identification using microsatellite DNA markers freely accessible at
      http://cabin.iasri.res.in/gomi/. CONCLUSION: Higher number of loci is required
      due to less differentiable population and large number of breeds taken in this
      study. This server will reduce the cost with computational ease. This methodology
      can be a model for various other domestic animal species as a valuable tool for
      conservation and breed improvement programmes.

PMID- 24320219
TI  - Comprehensive laboratory evaluation of a highly specific lateral flow assay for
      the presumptive identification of ricin in suspicious white powders and
      environmental samples.
AB  - Ricin, a heterodimeric toxin that is present in the seeds of the Ricinus communis
      plant, is the biothreat agent most frequently encountered by law enforcement
      agencies in the United States. Even in untrained hands, the easily obtainable
      seeds can yield a highly toxic product that has been used in various types of
      threats, including "white-powder" letters. Although the vast majority of these
      threats are hoaxes, an impediment to accurate hazard assessments by first
      responders is the unreliability of rapid detection assays for ricin, such as
      lateral flow assays (LFAs). One of the complicating factors associated with LFAs
      is the incorporation of antibodies of poor specificity that cross-react with near
      neighbors or with plant lectins that are capable of nonspecifically cross-linking
      the capture and detector antibodies. Because of the compelling and critical need
      to promote the interests of public safety and public health, the Department of
      Homeland Security conducted a comprehensive laboratory evaluation study of a
      commercial LFA for the rapid detection of ricin. This study was conducted using
      comprehensive inclusivity and exclusivity panels of ricin and near-neighbor plant
      materials, along with panels of lectins and "white-powders," to determine the
      specificity, sensitivity, limits of detection, dynamic range, and repeatability
      of the assay for the specific intended use of evaluating suspicious white powders
      and environmental samples in the field. 

PMID- 24320220
TI  - Effect of amphetamine on corrected-QT interval change during methadone
      maintenance treatment in Taiwan: a prospective cohort study.
AB  - INTRODUCTION AND AIMS: Previous studies have suggested that methadone is
      associated with prolonged corrected-QT (QTc) interval, but published prospective
      research studies in this area are relatively scarce. This study investigates QTc
      interval change among methadone maintenance patients and possible associated risk
      factors. One of the aims is to explore the effect of amphetamines. DESIGN AND
      METHODS: This prospective cohort study with six-month follow up assesses the
      effect of methadone on QTc interval among a sample (n = 170) of heroin users in a
      methadone maintenance treatment program in Taiwan. Demographic data, substance
      use history, medical history and laboratory studies were collected at study
      enrollment. Twelve-lead electrocardiograms were performed for all participants
      both at study enrollment and six months later. RESULTS: The median daily
      methadone dose was 41 mg. A mean increase of QTc interval (17.1 ms, SD = 50.0, P
      < 0.001) was found at six-month follow up. QTc interval prolongation in the
      sample at baseline was 2.9%, and at six months was 12.4%. A positive correlation
      was found between comorbid amphetamine use frequency in the past month and QTc
      interval change. Methadone dose was not associated with QTc change. DISCUSSION
      AND CONCLUSIONS: An increase of mean QTc interval was found among methadone
      maintenance patients at six-month follow up. Electrocardiogram monitoring should
      be performed among patients who are at risk of frequently using amphetamines
      during methadone maintenance treatment.

PMID- 24320221
TI  - Formulation and characterization of nanoemulsion intranasal adjuvants: effects of
      surfactant composition on mucoadhesion and immunogenicity.
AB  - The development of effective intranasal vaccines is of great interest due to
      their potential to induce both mucosal and systemic immunity. Here we produced
      oil-in-water nanoemulsion (NE) formulations containing various cationic and
      nonionic surfactants for use as adjuvants for the intranasal delivery of vaccine
      antigens. NE induced immunogenicity and antigen delivery are believed to be
      facilitated through initial contact interactions between the NE droplet and
      mucosal surfaces which promote prolonged residence of the vaccine at the site of
      application, and thus cellular uptake. However, the details of this mechanism
      have yet to be fully characterized experimentally. We have studied the
      physicochemical properties of the NE droplet surfactant components and
      demonstrate that properties such as charge and polar headgroup geometry influence
      the association of the adjuvant with the mucus protein, mucin. Association of NE
      droplets with mucin in vitro was characterized by various biophysical and imaging
      methods including dynamic light scattering (DLS), zeta potential (ZP), and
      surface plasmon resonance (SPR) measurements as well as transmission electron
      microscopy (TEM). Emulsion surfactant compositions were varied in a systematic
      manner to evaluate the effects of hydrophobicity and polar group charge/size on
      the NE-mucin interaction. Several cationic NE formulations were found to
      facilitate cellular uptake of the model antigen, ovalbumin (OVA), in a nasal
      epithelial cell line. Furthermore, fluorescent images of tissue sections from
      mice intranasally immunized with the same NEs containing green fluorescent
      protein (GFP) antigen demonstrated that these NEs also enhanced mucosal layer
      penetration and cellular uptake of antigen in vivo. NE-mucin interactions
      observed through biophysical measurements corresponded with the ability of the NE
      to enhance cellular uptake. Formulations that enhanced antigen uptake in vitro
      and in vivo also led to the induction of a more consistent antigen specific
      immune response in mice immunized with NEs containing OVA, linking NE-facilitated
      mucosal layer penetration and cellular uptake to enhancement of the immune
      response. These findings suggest that biophysical measurement of the mucoadhesive
      properties of emulsion based vaccines constitutes an effective in vitro strategy
      for selecting NE candidates for further evaluation in vivo as mucosal adjuvants. 

PMID- 24320222
TI  - Outcomes of single-stage compared to two-stage basilic vein transposition
      fistulae.
AB  - Basilic vein transposition (BVT) fistulae are increasing in prevalence in the
      United States. We examined outcomes of BVT fistulae created in a single stage
      compared to those created in two stages. Prospective QA databases identified a
      consecutive cohort of 144 patients with BVT fistulae. Of these, 42% were created
      in one stage and 58% in two stages. Fistula maturation rates, mean time to
      fistula use and intensity of percutaneous interventions were compared; patency
      rates were compared from time of first intervention. Maturation rates (including
      assisted maturation) were 90% among 1-stage and 75% among 2-stage BVT (p = 0.02).
      Mean time to initiation of fistula use was 142 days (1-stage) and 146 days (2
      stage) (p = 0.92). Intensity of percutaneous interventions was 1.84/patient-year
      of dialysis (PYD) (1-stage) and 2.15/PYD (2-stage) (p = 0.57). Secondary patency
      at 1, 2, 3, and 4 years for 1-stage BVT was 86%, 75%, 69%, and 57%; secondary
      patency at 1, 2, 3, and 4 years for 2-stage BVT was 76%, 71%, 49%, and 25%,
      respectively (p = 0.12). BVT creation in two stages confers only a modest
      reduction in maturation rates and secondary patency and therefore should be
      considered over a synthetic graft in patients with basilic veins deemed
      inadequate for 1-stage BVT.

PMID- 24320223
TI  - Validity and acceptability of a high-fidelity physical simulation model for
      training of laparoscopic pyeloplasty.
AB  - PURPOSE: The objective was to determine the acceptability and preliminary
      construct validity for a high-fidelity synthetic renal pelvis/ureter tissue
      analogue model for use as a simulation model for training of laparoscopic
      pyeloplasty. MATERIALS AND METHODS: The pyeloplasty model was designed with
      incorporated assessment lines for use in post-task Black Light Assessment of
      Surgical Technique (BLAST)TM. Practicing urologists participating in the 2011 and
      2012 American Urological Association Mentored Renal Laparoscopy courses performed
      a simulated laparoscopic pyeloplasty procedure and completed a post-task
      evaluation of the model. RESULTS: Practicing urologists found the model
      acceptable and rated the model favorably in terms of content and face validity.
      Urologists who had performed a laparoscopic pyeloplasty procedure in the last 5
      years outperformed those who had not by demonstrating increased patency (P<0.05),
      decreased twisting (P<0.05), and decreased leakage (P<0.10) at the anastomosis.
      CONCLUSIONS: The BLASTTM pyeloplasty model demonstrated evidence of acceptability
      and content, face, and construct validity for training practicing urologists to
      perform laparoscopic pyeloplasty.

PMID- 24320225
TI  - Synthesis, structure, and reactivity of a terminal organozinc fluoride compound:
      hydrogen bonding, halogen bonding, and donor-acceptor interactions.
AB  - [Tris(2-pyridylthio)methyl]zinc fluoride, [kappa(4)-Tptm]ZnF, the first example
      of an organozinc compound that features a terminal fluoride ligand, may be
      obtained by the reactions of either [Tptm]ZnX (X = H, OSiMe3) with Me3SnF or
      [kappa(4)-Tptm]ZnI with [Bu(n)4N]F. Not only is the fluoride ligand of [kappa(4)
      Tptm]ZnF susceptible to coordination by B(C6F5)3 to give the adduct [kappa(4)
      Tptm]ZnFB(C6F5)3, but it is also an effective hydrogen bond and halogen bond
      acceptor. For example, X-ray diffraction studies demonstrate that [kappa(4)
      Tptm]ZnF forms an adduct with water in which hydrogen bonding between the
      fluoride ligands and water molecules serves to link pairs of [kappa(4)-Tptm]ZnF
      molecules with a [F...(H-O-H)2...F] motif. Furthermore, (1)H and (19)F NMR
      spectroscopic studies provide evidence for hydrogen bonding and halogen bonding
      interactions with indole and C6F5I, respectively. 

PMID- 24320224
TI  - South-East Asia is the center of origin, diversity and dispersion of the rice
      blast fungus, Magnaporthe oryzae.
AB  - * Inferring invasion routes and identifying reservoirs of diversity of plant
      pathogens are essential in proposing new strategies for their control.
      Magnaporthe oryzae, the fungus responsible for rice blast disease, has invaded
      all rice growing areas. Virulent genotypes regularly (re)emerge, causing rapid
      resistance breakdowns. However, the world-wide genetic subdivision of M. oryzae
      populations on rice and its past history of invasion have never been elucidated.
      * In order to investigate the centers of diversity, origin and migration of M.
      oryzae on rice, we analyzed the genetic diversity of 55 populations from 15
      countries. * Three genetic clusters were identified world-wide. Asia was the
      center of diversity and the origin of most migrations to other continents. In
      Asia, two centers of diversity were revealed in the Himalayan foothills: South
      China-Laos-North Thailand, and western Nepal. Sexual reproduction persisted only
      in the South China-Laos-North Thailand region, which was identified as the
      putative center of origin of all M. oryzae populations on rice. * Our results
      suggest a scenario of early evolution of M. oryzae on rice that matches the past
      history of rice domestication. This study confirms that crop domestication may
      have considerable influence on the pestification process of natural enemies.

PMID- 24320226
TI  - Prospective study of the MD-twin score for antepartum evaluation of monochorionic
      diamniotic twins and its correlation with perinatal outcomes.
AB  - AIM: To assess the outcome of monochorionic diamniotic (MD) twins with the aid of
      the MD-twin score. METHODS: We enrolled 112 MD-twin women in a tertiary perinatal
      center from 1997 to 2009. The MD-twin score was prospectively applied once per
      week to women who did not have twin-to-twin transfusion syndrome (TTTS) after 26
      weeks of gestation. The MD-twin score consists of five variables: (i) fetal
      weight discordance; (ii) amniotic fluid discordance; (iii) hydrops fetalis; (iv)
      umbilical cord insertion; and (v) fetal heart rate monitoring. Normal was
      assigned a value of 0, abnormal was assigned 1, and total score was used for
      evaluation. Women with scores of 2 at 26 weeks gestation were managed expectantly
      until the score reached 3. Outcome measures were fetal death, neonatal death and
      neurological sequelae. The incidence of poor outcome according to score was
      investigated. The characteristics of MD twins with poor outcome were
      investigated. RESULTS: MD-twin scores were applied to 90 women. Among them, 79
      had scores of 2 or less and all had good outcomes. There were 11 women with a
      score of 3, four of whom had adverse outcome for at least one twin. Neonates born
      to women with scores of 0-2 had good outcomes without respect to birthweight
      percentile, while neonates with scores of 3 had poor outcomes when their
      birthweight percentile was less than the third percentile. CONCLUSION: The MD
      twin score is applicable to 90% of MD twins without TTTS. An MD-twin score of 2
      is reassuring, while a score of 3 indicates increased risks for adverse outcome.

PMID- 24320227
TI  - Structural characterization of a novel polysaccharide from pulp tissues of Litchi
      chinensis and its immunomodulatory activity.
AB  - A novel polysaccharide (LCP50W) with a molecular weight of 4.72 * 10(4) Da was
      isolated from the pulp tissues of Litchi chinensis . The chemical structure of
      LCP50W was characterized using physicochemical and instrumental analyses. The
      results indicated that the main chain of LCP50W consisted of (1->3)-linked beta-L
      rhamnopyranosyl, (1->6)-linked alpha-D-glucopyranosyl, and (1->2,6)-linked alpha
      D-glucopyranosyl residues, which branched at O-6. The three branches consisted of
      (1->2)-linked alpha-L-rhamnopyranosyl, (1->3)-linked alpha-D-galactopyranosyl,
      and (1->3)-linked alpha-L-mannopyranosyl residues, terminated with (1->)-linked
      alpha-L-arabinopyranosyl residues, respectively. The in vitro immunomodulatory
      assay revealed that LCP50W promoted the proliferation of mouse splenocytes and
      enhanced the cytotoxicity of NK cells. LCP50W boosted the secretion of Th1
      cytokine IFN-gamma while it inhibited the secretion of Th2 cytokine IL-4; it also
      enhanced the expression of T-bet while it inhibited the expression of GATA-3.
      Additionally, LCP50W promoted the development of cell cycle toward the S phase.

PMID- 24320228
TI  - A frameshift mutation in the melanophilin gene causes the dilute coat colour in
      rabbit (Oryctolagus cuniculus) breeds.
AB  - In rabbit, the dilute locus is determined by a recessive mutated allele (d) that
      causes the dilution of both eumelanic and pheomelanic pigmentations. In mice,
      similar phenotypes are determined by mutations in the myosin VA, Rab27a and
      melanophilin (MLPH) genes. In this study, we investigated the rabbit MLPH gene
      and showed that a mutation in this gene appears responsible for the dilute coat
      colour in this species. Checkered Giant F1 families segregating for black and
      grey (diluted or blue) coat colour were first genotyped for a complex indel in
      intron 1 of the MLPH gene that was completely associated with the coat colour
      phenotype (theta = 0.00; LOD = 4.82). Then, we sequenced 6357 bp of the MLPH gene
      in 18 rabbits of different coat colours, including blue animals. A total of 165
      polymorphisms were identified: 137 were in non-coding regions and 28 were in
      coding exons. One of them was a frameshift deletion in exon 5. Genotyping the
      half-sib families confirmed the complete cosegregation of this mutation with the
      blue coat colour. The mutation was analysed in 198 rabbits of 23 breeds. All Blue
      Vienna and all other blue/grey/ash rabbits in other breeds (Californian, Castor
      Rex, Checkered Giant, English Spot, Fairy Marburg and Fairy Pearly) were
      homozygous for this deletion. The identification of MLPH as the responsible gene
      for the dilute locus in rabbit provides a natural animal model for human
      Griscelli syndrome type 3 and a new mutant to study the role of this gene on
      pigmentation.

PMID- 24320229
TI  - The mechanism by which the phenothiazine thioridazine contributes to cure
      problematic drug-resistant forms of pulmonary tuberculosis: recent patents for
      "new use".
AB  - At this moment, over half million patients suffer from multi-drug resistant
      tuberculosis (MDR-TB) according to the data from the WHO. A large majority is
      terminally ill with essentially incurable pulmonary tuberculosis. This herein
      mini-review provides the experimental and observational evidence that a specific
      phenothiazine, thioridazine, will contribute to cure any form of drug-resistant
      tuberculosis. This antipsychotic agent is no longer under patent protection for
      its initial use. The reader is informed on the recent developments in patenting
      this compound for "new use" with a special emphasis on the aspects of drug
      resistance. Given that economic motivation can stimulate the use of this drug as
      an antitubercular agent, future prospects are also discussed. 

PMID- 24320230
TI  - Novel quercetin glycosides as potent anti-MRSA and anti-VRE agents.
AB  - Each year in the United States, at least 2 million people become infected with
      bacteria that are resistant to antibiotics and at least 23,000 people die each
      year as a direct result of these infections (Threat report 2013). Vancomycin is
      an FDA approved antibiotic and is growing importance in the treatment of hospital
      infections, with particular emphasis on its value to fight against methicillin
      resistant Staphylococcus aureus (MRSA). The increasing use of vancomycin to treat
      infections caused by the Gram-positive MRSA in the 1970s selected for drug
      resistant enterococci, less potent than staphylococci but opportunistic in the
      space vacated by other bacteria and in patients with compromised immune systems.
      The dramatic rise of antibiotic-resistant bacteria over the past two decades has
      stressed the need for completely novel classes of antibacterial agents. This
      paper reports the recent patent review on the strategy for finding novel
      quercetinglycoside type antibacterial agents against vancomycin-resistant
      bacterial strains. 

PMID- 24320231
TI  - Histologic outcomes of excised moderate and severe dysplastic nevi.
AB  - BACKGROUND: Dysplastic nevi (DN) have been a matter of controversy since their
      initial description in 1978 because of differences in the clinical and
      histological terminology, and large studies on histological outcomes of excising
      moderate to severely DN have not previously been described. OBJECTIVE: To
      determine the clinical characteristics of DN and histologic outcomes of excised
      moderate and severe DN. METHODS: Retrospective chart review of patients with DN
      or Clark's nevi at the Dermatology Department at Rutgers-Robert Wood Johnson
      Medical School in Somerset, New Jersey, from January 2009 to June 2012. Three
      hundred ninety-three lesions from 380 patients were included in this study. MAIN
      OUTCOME MEASURE: Histologic results of excised moderate and severe DN. RESULTS:
      Thirty-four percent of DN were excised because of the presence of moderate or
      severe atypia, personal history of melanoma, or both. None of the excised lesions
      showed evidence of melanoma; 81.6% of excisions showed scar or granulation
      tissue. Only 14% of excised lesions were found to have residual lesions, and 4.4%
      showed recurrent nevi. CONCLUSION: In 134 excisions of moderate to severe DN, no
      melanoma was identified. Most of the excisions showed scar or granulation tissue.
      The rate of residual lesions after shave biopsy of moderate or severe DN was
      lower than after punch biopsy.

PMID- 24320232
TI  - In vivo neuron-wide analysis of synaptic vesicle precursor trafficking.
AB  - During synapse development, synaptic proteins must be targeted to sites of
      presynaptic release. Directed transport as well as local sequestration of
      synaptic vesicle precursors (SVPs), membranous organelles containing many
      synaptic proteins, might contribute to this process. Using neuron-wide time-lapse
      microscopy, we studied SVP dynamics in the DA9 motor neuron in Caenorhabditis
      elegans. SVP transport was highly dynamic and bi-directional throughout the
      entire neuron, including the dendrite. While SVP trafficking was anterogradely
      biased in axonal segments prior to the synaptic domain, directionality of SVP
      movement was stochastic in the dendrite and distal axon. Furthermore, frequency
      of movement and speed were variable between different compartments. These data
      provide evidence that SVP transport is differentially regulated in distinct
      neuronal domains. It also suggests that polarized SVP transport in concert with
      local vesicle capturing is necessary for accurate presynapse formation and
      maintenance. SVP trafficking analysis of two hypomorphs for UNC-104/KIF1A in
      combination with mathematical modeling identified directionality of movement,
      entry of SVPs into the axon as well as axonal speeds as the important
      determinants of steady-state SVP distributions. Furthermore, detailed dissection
      of speed distributions for wild-type and unc-104/kif1a mutant animals revealed an
      unexpected role for UNC-104/KIF1A in dendritic SVP trafficking. 

PMID- 24320233
TI  - Organic synthesis of maize starch-based polymer using Rhizopus oryzae lipase,
      scale up, and its characterization.
AB  - The industrial utilization of native starches is limited because of their inherit
      nature, with characteristics such as water insolubility and their tendency to
      form unstable pastes and gels. In this investigation, a lipase produced from
      Rhizopus oryzae was used for modification of maize starch with palmitic acid at a
      reaction temperature of 45 degrees C for 18 hr in the presence of dimethyl
      sulfoxide (DMSO). The synthesis of maize starch palmitate was confirmed by
      Fourier-transform infrared (FT-IR) and (1)H-nuclear magnetic resonance (NMR)
      spectra with a higher degree of substitution (DS) of 1.68. Thermal gravimetric
      analysis (TGA) showed that the maize starch palmitate is more stable even up to
      496 degrees C as compared to unmodified maize starch (231.4 degrees C). Maize
      starch palmitate possesses high degree of substitution and thermal properties and
      thus can be widely used in food and pharmaceutical industry.

PMID- 24320234
TI  - Evaluation of biotechnological potentials of some industrial fungi in economical
      lipid accumulation and biofuel production as a field of use.
AB  - Considering the vast number of scientific reports on various potential uses of
      fungi, there was an attempt to select the best lipid producer of some fungi at
      optimized conditions (Aspergillus versicolor, Rhizopus oryzae, Rhizopus arrhizus,
      Tramates versicolor). The aim was to offer new fields of use to the industries
      already culturing and using such materials. Aspergillus versicolor mycelia were
      found to be accumulating the highest amount of lipids. Experiments to improve
      lipid accumulation and transesterification properties were performed in molasses
      medium; the first steps were testing the effects of different pH values and
      different nitrogen sources on lipid accumulation. Various concentrations of
      KNO(3) (0.5, 1.0, 1.5 gL(-1)) and molasses (6%, 8%, 10%) were tried in order to
      find the optimum carbon and nitrogen requirements. Maximum lipid content was
      22.8% in the samples containing 6% molasses solution and 1.0 gL(-1) KNO(3) at pH
      4 after 10 days of incubation. The highest fatty acid ethyl ester yield of these
      samples was 77% (5.0 ethanol:oil, 0.4 sulfuric acid:oil at 30 degrees C for 6
      hr). Since the crude lipids were rich in C16 and C18 fatty acids, this was
      considered as suitable feedstock for biodiesel production.

PMID- 24320235
TI  - Optimization of medium composition for cis,cis-muconic acid production by a
      Pseudomonas sp. mutant using statistical methods.
AB  - cis,cis-Muconic acid (CCMA) is used as a platform chemical for the production of
      several high-value compounds. For this article, an optimization strategy has been
      used to optimize medium composition for CCMA production from fairly cheap
      benzoate by Pseudomonas sp. 1167. The effect of different concentrations of
      medium components on CCMA production was studied. CCMA yields obtained from
      Plackett-Burman design (PBD) showed wide variation (3.95-5.87 g/L), and the first
      order model indicated that (NH(4))(2)SO(4) (P < 0.01) and K(2)HPO(4) . 3H(2)O (P
      < 0.02) were the significant components for CCMA production. Then the
      optimization was performed by steepest ascent design (SAD) and central composite
      design (CCD), and a validation experiment was conducted to verify the predicted
      value. The optimal medium composition was: 12 g/L sodium benzoate, 2.5 g/L sodium
      succinate, 0.7932 g/L (NH(4))(2)SO(4), 1.5612 g/L K(2)HPO(4) . 3H(2)O, 1.2 g/L
      MgSO(4) . 7H(2)O, 0.4 g/L yeast extract, 0.08 g/L FeCl(3) . 6H(2)O, and 0.08 g/L
      ethylenediamine tetraacetic acid (EDTA). Under these conditions, a maximum of
      7.18 g/L CCMA was produced per 12 g/L benzoate with a highly efficient process
      within 11 hr and a molecular conversion yield of 61%. Altogether, our results
      provide valuable insights into nutritional supplementation of CCMA production by
      using statistical methods, which may benefit a cost-competitive industrial fed
      batch fermentation process using a cheap substrate.

PMID- 24320236
TI  - Carotene production from agro-industrial wastes by Arthrobacter globiformis in
      shake-flask culture.
AB  - Industrial waste substrates, sugarcane molasses, and corn steep liquor were used
      for production of carotenes by Arthrobacter globiformis in this study. At the
      first stage, a one-factor-at-a-time approach was used for optimization of
      different media components such as carbon, nitrogen, MgSO(4) . 7H(2)O, and
      KH(2)PO(4), as well as pH, temperature, liquid medium volume, and inoculums
      level. The response surface method was further applied to determination of
      optimum values of process variables for maximum carotenes concentration. Results
      showed that the optimum combination for carotenes formation was as follows (g/L):
      sugarcane molasses, 40.00; corn steep liquor, 50.00; MgSO(4) . 7H(2)O, 0.75;
      KH(2)PO(4), 1.00. The maximum carotene concentration of 1.19 +/- 0.02 mg/g dry
      biomass, about 113% of 1.05 +/- 0.02 mg/g dry biomass growing in basal medium,
      was demonstrated by confirmatory experiments to be the optimum in liquid medium
      at 100 rpm, 30 degrees C, initial pH of 7.5, and cultivation for 60 hr. In a
      second stage, detailed studies showed about 1.64-fold and 1.43-fold increase in
      carotene concentration (mg/g dry biomass) in the presence of addition of ethanol
      (4%, v/v) and addition of hydrogen peroxide (4%, v/v) at 40 hr, and 32 hr in
      liquid medium, separately.

PMID- 24320237
TI  - Efficient production of Staphylococcus simulans lysostaphin in a benchtop
      bioreactor by recombinant Escherichia coli.
AB  - Lysostaphin is an enzyme with bactericidal activity against Staphylococcus aureus
      and other staphylococcal species. In spite of many advantages and promising
      results of preliminary research, the enzyme is still not widely used in medicine,
      veterinary medicine, or as a food preservative. One of the most important factors
      limiting application of the enzyme in clinical or technological practice is the
      high cost of its production. In this study we have determined the optimal
      conditions for lysostaphin production in a 5-L batch bioreactor. The enzyme
      production was based on a heterologous, Escherichia coli expression system
      designated as pBAD2Lys and constructed earlier in our laboratory. An evident
      influence of physicochemical conditions of the process (areation, pH and
      temperature) and composition of the growing media on the amount and activity of
      produced enzyme was noticed. Efficiency of production of about 13,000 U/L has
      been achieved in the optimal conditions of the production process: low aeration
      (400 rpm of mechanical stirrer), pH 6, and temperature 37 degrees C in classical
      LB medium. Further, about twofold improvement in the production efficiency of the
      enzyme was achieved as a result of modification of composition of growing media.
      Finally, more than 80,000 units of lysostaphin were obtained from one (batch)
      bioreactor with 3 L of culture of E. coli TOP10F' transformed with pBAD2Lys
      plasmid. To the best of our knowledge, this is the most efficient method of
      production of recombinant lysostaphin in E. coli expression systems described to
      date.

PMID- 24320238
TI  - Production and characterization of L-fucose dehydrogenase from newly isolated
      Acinetobacter sp. strain SA-134.
AB  - Microorganisms producing L-fucose dehydrogenase were screened from soil samples,
      and one of the isolated bacterial strains SA-134 was identified as Acinetobacter
      sp. by 16S rDNA gene analysis. The strain grew well utilizing L-fucose as a sole
      source of carbon, but all other monosaccharides tested such as D-glucose and D
      arabinose did not support the growth of the strain in the absence of L-fucose. D
      Arabinose inhibited the growth even in the culture medium containing L-fucose.
      Although the strain grew on some organic acids and amino acids such as citric
      acid and L-alanine as sole sources of carbon, the enzyme was produced only in the
      presence of L-fucose. The fucose dehydrogenase was purified to apparently
      homogeneity from the strain, and the native enzyme was a monomer of 25 kD. L
      Fucose and D-arabinose were good substrates for the enzyme, but L-galactose was a
      poor substrate. The enzyme acted on both NAD(+) and NADP(+) in the similar
      manner.

PMID- 24320239
TI  - Cost-effective endo-mannanase from Bacillus sp. CFR1601 and its application in
      generation of oligosaccharides from guar gum and as detergent additive.
AB  - The indigenous bacteria Bacillus sp. CFR1601 produced significant levels of endo
      mannanase when grown on agro-wastes, namely, green gram husk and sunflower oil
      cake (25.6 IU/mL), used as sole carbon and nitrogen sources, respectively. Under
      immobilized cell system, synthetic supports (polyurethane foam, scotch brite,
      polyester; up to 33.2 IU/mL) were found marginally superior as compared to
      natural supports (cotton and silk; up to 28.2 IU/mL) for endo-mannanase
      production. Cooperative interactions between L-lysine HCl (0.3% w/v), Tween 60
      (0.3% v/v), and sunflower oil cake (3.0% w/v) in central composite design
      response surface methodology ameliorated (1.61-fold) endo-mannanase titers to
      48.0 IU/mL. Partially purified endo-mannanase was tested for its ability to
      produce oligosaccharides from guar gum. These oligosaccharides were tested in
      vitro for their ability to promote growth of Lactobacillus plantarum MTCC 5422
      and Lactobacillus salivarius CHS 1E. Results indicated that low-molecular-weight
      degraded products from guar gum were (1) able to support the growth of tested
      strains [increased O.D600nm up to 2.3-fold and decrease in pH (<6.3) due to
      production of short chain fatty acid (SCFA)] when used as sole carbon source; and
      (2) after purification and analysis by electron spray ionization-mass
      spectrometry (ESI-MS) were found to be composed of mainly disaccharide and
      tetrasaccharide. The compatibility of endo-mannanase with various detergents
      together with wash performance test confirmed its potential applicability for
      laundry industry. 

PMID- 24320240
TI  - A quick, efficient, and cost-effective method for isolating high-quality total
      RNA from tomato fruits, suitable for molecular biology studies.
AB  - Tomato (Solanum lycopersicum L.) is the primary model for the study of fleshy
      fruits, and research on this species has elucidated many aspects of fruit
      physiology, development, and metabolism. However, for advancing such studies at
      molecular biology levels, the RNA isolation from fruit tissues is often
      essential. The RNA isolation from tomato fruits is complicated because of the
      presence of high levels of polysaccharides, polyphenolics, pigments, and
      secondary metabolites and also the varying water content during development.
      Here, we present an optimized protocol for the isolation of total RNA from the
      fruit tissues at different developmental stages. In comparison to the previous
      methods described for the RNA isolation from tomato fruit, this method has the
      advantages that it does not involve the use of guanidine salts, lyophilizers, and
      commercial reagents, reduces the time and cost of extraction, overcomes the high
      water content problem, and promotes RNA quality by inhibiting RNA degradation and
      minimizing the gDNA, polyphenolic and polysaccharide contaminations. Using this
      method, high yields of high-purity and intact RNA samples were obtained as
      confirmed by the spectrophotometric readings and the electrophoresis on
      denaturing agarose gels. The isolated RNA was employed as a robust template for
      cDNA synthesis, reverse transcriptase-polymerase chain reaction (RT-PCR), and
      temporal gene expression analysis. The functionality of the isolated RNA was
      further demonstrated through cloning full-length cDNAs encoding beta
      galactosidase proteins by RT-PCR and sequencing. 

PMID- 24320241
TI  - How does the therapeutic alliance develop throughout cognitive behavioral therapy
      for panic disorder? Sawtooth patterns, sudden gains, and stabilization.
AB  - OBJECTIVE: There has been little research on the development of the therapeutic
      alliance in cognitive behavioral therapy (CBT). This study aims to examine the
      development of therapeutic alliance in CBT for panic disorder. METHOD: Nineteen
      patients were treated with CBT for panic disorder. Pre- and post-session data of
      the therapeutic alliance and panic symptoms and cognitions were collected.
      RESULTS: Several patterns were observed, including a sawtooth pattern (within
      session improvements followed by decline between sessions; 63% of the patients),
      sudden gains in the alliance (58%), and late stabilization (89%). The sawtooth
      pattern was related to less symptom reduction between sessions (explained
      variance = 20-48%). Though not statistically significant, there were moderate
      effect sizes for the relationships between outcomes and early alliance and sudden
      gains (explained variance = 13-17%). CONCLUSIONS: Overall, results suggest that
      intensive data collection is likely to yield understanding of the relationship
      between therapy processes and outcomes.

PMID- 24320242
TI  - Order-disorder transition and weak ferromagnetism in the perovskite metal formate
      frameworks of [(CH3)2NH2][M(HCOO)3] and [(CH3)2ND2][M(HCOO)3] (M = Ni, Mn).
AB  - We report the synthesis, crystal structure, thermal, dielectric, Raman, infrared,
      and magnetic properties of hydrogen and deuterated divalent metal formates,
      [(CH3)2NH2][M(HCOO)3] and [(CH3)2ND2][M(HCOO)3], where M = Ni, Mn. On the basis
      of Raman and IR data, assignment of the observed modes to respective vibrations
      of atoms is proposed. The thermal studies show that for the Ni compounds
      deuteration leads to a decrease of the phase transition temperature Tc by 5.6 K,
      whereas it has a negligible effect on Tc in the Mn analogues. This behavior
      excludes the possibility of proton (deuteron) movement along the N-H...O (N
      D...O) bonds as the microscopic origin of the first-order phase transition
      observed in these crystals below 190 K. According to single-crystal X-ray
      diffraction, the dimethylammonium (DMA) cations are dynamically disordered at
      room temperature, because the hydrogen bonds between the NH2 (ND2) groups and the
      metal-formate framework are disordered. The highly dynamic nature of hydrogen
      bonds in the high-temperature phases manifests in the Raman and IR spectra
      through very large bandwidth of modes involving vibrations of the NH2 (ND2)
      groups. The abrupt decrease in the bandwidth and shifts of modes near Tc
      signifies the ordering of hydrogen bonds and DMA(+) cations as well as
      significant distortion of the metal-formate framework across the phase
      transition. However, some amount of motion is retained by the DMA(+) cation in
      the ferroelectric phase and a complete freezing-in of this motion occurs below
      100 K. The dielectric studies reveal pronounced dielectric dispersion that can be
      attributed to slow dynamics of large DMA(+) cations. The low-temperature studies
      also show that magnetic properties of the studied compounds can be explained
      assuming that they are ordered ferrimagnetically with nearly compensated magnetic
      moments of Ni and Mn. IR data reveal weak anomalies below 40 K that arise due to
      spin-phonon coupling. Our results also show that due to structural phase
      transition more significant distortion of the metal-formate framework occurs for
      the deuterated samples. 

PMID- 24320243
TI  - A closer look at depictions of Cosmas and Damian.

PMID- 24320245
TI  - Communication: a Jastrow factor coupled cluster theory for weak and strong
      electron correlation.
AB  - We present a Jastrow-factor-inspired variant of coupled cluster theory that
      accurately describes both weak and strong electron correlation. Compatibility
      with quantum Monte Carlo allows for variational energy evaluations and an
      antisymmetric geminal power reference, two features not present in traditional
      coupled cluster that facilitate a nearly exact description of the strong electron
      correlations in minimal-basis N2 bond breaking. In double-zeta treatments of the
      HF and H2O bond dissociations, where both weak and strong correlations are
      important, this polynomial cost method proves more accurate than either
      traditional coupled cluster or complete active space perturbation theory. These
      preliminary successes suggest a deep connection between the ways in which cluster
      operators and Jastrow factors encode correlation. 

PMID- 24320244
TI  - Effect of NaCl stress on health-promoting compounds and antioxidant activity in
      the sprouts of three broccoli cultivars.
AB  - Health-promoting compounds, antioxidant and myrosinase activity in the sprouts of
      three broccoli cultivars under 40 mM, 80 mM and 160 mM NaCl were investigated.
      LangYan (LY) sprouts had the richest health-promoting compounds among the
      evaluated cultivars. Treatment of 40 mM and 80 mM NaCl significantly decreased
      the content of ascorbic acid and total phenolic as well as antioxidant activity,
      but did not affect glucoraphanin, sulforaphane and myrosinase activity compared
      to the control. However, 160 mM NaCl treatment significantly enhanced the level
      of total phenolic, glucoraphanin, sulforaphane, antioxidant and myrosinase
      activity, while significantly decreased ascorbic acid content. The results
      suggest that 160 mM NaCl treatment would enhance antioxidant activity and
      sulforaphane yield in broccoli sprouts. The health-promoting value of broccoli
      sprouts depends on plant genotype and could be affected by NaCl stress.

PMID- 24320246
TI  - Communication: nuclear quadrupole moment-induced Cotton-Mouton effect in noble
      gas atoms.
AB  - New, high-sensitivity and high-resolution spectroscopic and imaging methods may
      be developed by exploiting nuclear magneto-optic effects. A first-principles
      electronic structure formulation of nuclear electric quadrupole moment-induced
      Cotton-Mouton effect (NQCME) is presented for closed-shell atoms. In NQCME,
      aligned quadrupole moments alter the index of refraction of the medium along with
      and perpendicular to the direction of nuclear alignment. The roles of basis-set
      convergence, electron correlation, and relativistic effects are investigated for
      three quadrupolar noble gas isotopes: (21)Ne, (83)Kr, and (131)Xe. The magnitude
      of the resulting ellipticities is predicted to be 10(-4)-10(-6) rad/(M cm) for
      fully spin-polarized nuclei. These should be detectable in the Voigt setup.
      Particularly interesting is the case of (131)Xe, in which a high degree of spin
      polarization can be achieved via spin-exchange optical hyperpolarization. 

PMID- 24320247
TI  - Communication: long-lived neutral H2 in hydrogen migration within methanol
      dication.
AB  - The ejection of triatomic hydrogen molecular ions HD2(+) and D3(+) from CD3OH(2+)
      is investigated by first-principle molecular dynamics simulation. Two C-D
      chemical bonds are found to be broken to form a neutral D2 moiety that vibrates,
      rotates, and moves for a relatively long period of time (20-330 fs) towards a
      transition state leading to the ejection of HD2(+) or D3(+). The formation of
      such a long-lived neutral D2 moiety within a hydrocarbon molecule interprets well
      the recent experimental findings of the long lifetime of doubly charged energized
      hydrocarbon molecules prior to the ejection of H3(+).

PMID- 24320248
TI  - Polyad quantum numbers and multiple resonances in anharmonic vibrational studies
      of polyatomic molecules.
AB  - In the theory of anharmonic vibrations of a polyatomic molecule, mixing the zero
      order vibrational states due to cubic, quartic and higher-order terms in the
      potential energy expansion leads to the appearance of more-or-less isolated
      blocks of states (also called polyads), connected through multiple resonances.
      Such polyads of states can be characterized by a common secondary integer quantum
      number. This polyad quantum number is defined as a linear combination of the zero
      order vibrational quantum numbers, attributed to normal modes, multiplied by non
      negative integer polyad coefficients, which are subject to definition for any
      particular molecule. According to Kellman's method [J. Chem. Phys. 93, 6630
      (1990)], the corresponding formalism can be conveniently described using vector
      algebra. In the present work, a systematic consideration of polyad quantum
      numbers is given in the framework of the canonical Van Vleck perturbation theory
      (CVPT) and its numerical-analytic operator implementation for reducing the
      Hamiltonian to the quasi-diagonal form, earlier developed by the authors. It is
      shown that CVPT provides a convenient method for the systematic identification of
      essential resonances and the definition of a polyad quantum number. The method
      presented is generally suitable for molecules of significant size and complexity,
      as illustrated by several examples of molecules up to six atoms. The polyad
      quantum number technique is very useful for assembling comprehensive basis sets
      for the matrix representation of the Hamiltonian after removal of all non
      resonance terms by CVPT. In addition, the classification of anharmonic energy
      levels according to their polyad quantum numbers provides an additional means for
      the interpretation of observed vibrational spectra. 

PMID- 24320249
TI  - Violation of the mass-action law in dilute chemical systems.
AB  - The mass-action law, which predicts the rates of chemical reactions, is widely
      used for modeling the kinetics of the chemical reactions and their stationary
      states, also for complex chemical reaction networks. However, violations of the
      mass-action equations have been reported in various cases: in confined systems
      with a small number of molecules, in non-ideally-stirred systems, when the
      reactions are limited by the diffusion, at high concentrations of reactants, or
      in chemical reaction networks with marginally stable mass-action equations. In
      this paper, I describe a new mechanism, leading to the violation of the mass
      action equations, that takes place at a low concentration of at least one of the
      reactants; in this limit, the reaction rates can be easily inferred from the
      chemical reaction network. I propose that this mechanism underlies the
      replication stability of the hypercycles, a class of chemical reaction networks
      hypothetically connected with abiogenesis. I provide two simple examples of
      chemical reaction networks in which the mechanism leading to the violation of the
      mass-action law is present. I study the two chemical reaction networks by means
      of a simulation performed with a cellular automaton model. The results have a
      general validity and represent a limitation of the validity of the mass-action
      law, which has been overlooked up to now in the studies about the chemical
      reaction networks. 

PMID- 24320251
TI  - Linear-scaling symmetry-adapted perturbation theory with scaled dispersion.
AB  - We present a linear-scaling symmetry-adapted perturbation theory (SAPT) method
      that is based on an atomic orbital (AO) formulation of zeroth-order SAPT (SAPT0).
      The non-dispersive terms are realized with linear-scaling cost using both the
      continuous fast multipole method (CFMM) and the linear exchange (LinK) approach
      for integral contractions as well as our efficient Laplace-based coupled
      perturbed self-consistent field method (DL-CPSCF) for evaluating response
      densities. The reformulation of the dispersion term is based on our linear
      scaling AO Moller-Plesset second-order perturbation theory (AO-MP2) method, that
      uses our recently introduced QQR-type screening [S. A. Maurer, D. S. Lambrecht,
      J. Kussmann, and C. Ochsenfeld, J. Chem. Phys. 138, 014101 (2013)] for
      preselecting numerically significant energy contributions. Similar to scaled
      opposite-spin MP2, we neglect the exchange-dispersion term in SAPT and introduce
      a scaling factor for the dispersion term, which compensates for the error and at
      the same time accounts for basis set incompleteness effects and intramonomer
      correlation. We show in extensive benchmark calculations that the new scaled
      dispersion (sd-)SAPT0 approach provides reliable results for small and large
      interacting systems where the results with a small 6-31G** basis are roughly
      comparable to supermolecular MP2 calculations in a triple-zeta basis. The
      performance of our method is demonstrated with timings on cellulose fragments,
      DNA systems, and cutouts of a protein-ligand complex with up to 1100 atoms on a
      single computer core.

PMID- 24320252
TI  - Characterizing N-dimensional anisotropic Brownian motion by the distribution of
      diffusivities.
AB  - Anisotropic diffusion processes emerge in various fields such as transport in
      biological tissue and diffusion in liquid crystals. In such systems, the motion
      is described by a diffusion tensor. For a proper characterization of processes
      with more than one diffusion coefficient, an average description by the mean
      squared displacement is often not sufficient. Hence, in this paper, we use the
      distribution of diffusivities to study diffusion in a homogeneous anisotropic
      environment. We derive analytical expressions of the distribution and relate its
      properties to an anisotropy measure based on the mean diffusivity and the
      asymptotic decay of the distribution. Both quantities are easy to determine from
      experimental data and reveal the existence of more than one diffusion
      coefficient, which allows the distinction between isotropic and anisotropic
      processes. We further discuss the influence on the analysis of projected
      trajectories, which are typically accessible in experiments. For the
      experimentally most relevant cases of two- and three-dimensional anisotropic
      diffusion, we derive specific expressions, determine the diffusion tensor,
      characterize the anisotropy, and demonstrate the applicability for simulated
      trajectories. 

PMID- 24320250
TI  - Calculating the binding free energies of charged species based on explicit
      solvent simulations employing lattice-sum methods: an accurate correction scheme
      for electrostatic finite-size effects.
AB  - The calculation of a protein-ligand binding free energy based on molecular
      dynamics (MD) simulations generally relies on a thermodynamic cycle in which the
      ligand is alchemically inserted into the system, both in the solvated protein and
      free in solution. The corresponding ligand-insertion free energies are typically
      calculated in nanoscale computational boxes simulated under periodic boundary
      conditions and considering electrostatic interactions defined by a periodic
      lattice-sum. This is distinct from the ideal bulk situation of a system of
      macroscopic size simulated under non-periodic boundary conditions with Coulombic
      electrostatic interactions. This discrepancy results in finite-size effects,
      which affect primarily the charging component of the insertion free energy, are
      dependent on the box size, and can be large when the ligand bears a net charge,
      especially if the protein is charged as well. This article investigates finite
      size effects on calculated charging free energies using as a test case the
      binding of the ligand 2-amino-5-methylthiazole (net charge +1 e) to a mutant form
      of yeast cytochrome c peroxidase in water. Considering different charge isoforms
      of the protein (net charges -5, 0, +3, or +9 e), either in the absence or the
      presence of neutralizing counter-ions, and sizes of the cubic computational box
      (edges ranging from 7.42 to 11.02 nm), the potentially large magnitude of finite
      size effects on the raw charging free energies (up to 17.1 kJ mol(-1)) is
      demonstrated. Two correction schemes are then proposed to eliminate these
      effects, a numerical and an analytical one. Both schemes are based on a continuum
      electrostatics analysis and require performing Poisson-Boltzmann (PB)
      calculations on the protein-ligand system. While the numerical scheme requires PB
      calculations under both non-periodic and periodic boundary conditions, the latter
      at the box size considered in the MD simulations, the analytical scheme only
      requires three non-periodic PB calculations for a given system, its dependence on
      the box size being analytical. The latter scheme also provides insight into the
      physical origin of the finite-size effects. These two schemes also encompass a
      correction for discrete solvent effects that persists even in the limit of
      infinite box sizes. Application of either scheme essentially eliminates the size
      dependence of the corrected charging free energies (maximal deviation of 1.5 kJ
      mol(-1)). Because it is simple to apply, the analytical correction scheme offers
      a general solution to the problem of finite-size effects in free-energy
      calculations involving charged solutes, as encountered in calculations
      concerning, e.g., protein-ligand binding, biomolecular association, residue
      mutation, pKa and redox potential estimation, substrate transformation,
      solvation, and solvent-solvent partitioning. 

PMID- 24320253
TI  - The instantaneous fluctuation theorem.
AB  - We give a derivation of a new instantaneous fluctuation relation for an arbitrary
      phase function which is odd under time reversal. The form of this new relation is
      not obvious, and involves observing the system along its transient phase space
      trajectory both before and after the point in time at which the fluctuations are
      being compared. We demonstrate this relation computationally for a number of
      phase functions in a shear flow system and show that this non-locality in time is
      an essential component of the instantaneous fluctuation theorem. 

PMID- 24320254
TI  - Asymptotic expansion of two-electron integrals and its application to Coulomb and
      exchange lattice sums in metallic, semimetallic, and nonmetallic crystals.
AB  - A simple, easily implemented, accurate, and efficient approximation of long-range
      electron-electron-repulsion and electron-nucleus-attraction integrals is
      proposed. It replaces each product of two atomic-orbital (AO) basis functions of
      an electron by a point charge centered at the midpoint of the two AO's. The
      magnitude of the point charge is equal to the overlap integral of the two AO's.
      Each integral is then rapidly evaluated in the direct algorithm as a Coulomb
      interaction between two point charges. This scheme is implemented in ab initio
      Hartree-Fock crystalline orbital theory and tested for one-, two-, and three
      dimensional solids of metallic, semimetallic, and nonmetallic electronic
      structures, in which the lattice sums of the direct Coulomb and/or exchange
      interactions are expected to be slowly convergent. It is shown that this
      approximation reduces operation and/or memory costs by up to an order of
      magnitude to achieve converged lattice sums, although the scaling (size
      dependence) of operation cost is unchanged. An improved criterion for truncating
      the exchange lattice sum is also proposed. 

PMID- 24320255
TI  - Assessment of G3(MP2)//B3 theory including a pseudopotential for molecules
      containing first-, second-, and third-row representative elements.
AB  - G3(MP2)//B3 theory was modified to incorporate compact effective potential (CEP)
      pseudopotentials, providing a theoretical alternative referred to as G3(MP2)//B3
      CEP for calculations involving first-, second-, and third-row representative
      elements. The G3/05 test set was used as a standard to evaluate the accuracy of
      the calculated properties. G3(MP2)//B3-CEP theory was applied to the study of 247
      standard enthalpies of formation, 104 ionization energies, 63 electron
      affinities, 10 proton affinities, and 22 atomization energies, comprising 446
      experimental energies. The mean absolute deviations compared with the
      experimental data for all thermochemical results presented an accuracy of 1.4
      kcal mol(-1) for G3(MP2)//B3 and 1.6 kcal mol(-1) for G3(MP2)//B3-CEP.
      Approximately 75% and 70% of the calculated properties are found with accuracy
      between +/-2 kcal mol(-1) for G3(MP2)//B3 and G3(MP2)//B3-CEP, respectively.
      Considering a confidence interval of 95%, the results may oscillate between +/
      4.2 kcal mol(-1) and +/-4.6 kcal mol(-1), respectively. The overall statistical
      behavior indicates that the calculations using pseudopotential present similar
      behavior with the all-electron theory. Of equal importance to the accuracy is the
      CPU time, which was reduced by between 10% and 40%. 

PMID- 24320256
TI  - Nonlinear intrinsic variables and state reconstruction in multiscale simulations.
AB  - Finding informative low-dimensional descriptions of high-dimensional simulation
      data (like the ones arising in molecular dynamics or kinetic Monte Carlo
      simulations of physical and chemical processes) is crucial to understanding
      physical phenomena, and can also dramatically assist in accelerating the
      simulations themselves. In this paper, we discuss and illustrate the use of
      nonlinear intrinsic variables (NIV) in the mining of high-dimensional multiscale
      simulation data. In particular, we focus on the way NIV allows us to functionally
      merge different simulation ensembles, and different partial observations of these
      ensembles, as well as to infer variables not explicitly measured. The approach
      relies on certain simple features of the underlying process variability to filter
      out measurement noise and systematically recover a unique reference coordinate
      frame. We illustrate the approach through two distinct sets of atomistic
      simulations: a stochastic simulation of an enzyme reaction network exhibiting
      both fast and slow time scales, and a molecular dynamics simulation of alanine
      dipeptide in explicit water. 

PMID- 24320257
TI  - Broken symmetry approach to density functional calculation of zero field
      splittings including anisotropic exchange interactions.
AB  - The broken symmetry approach to the calculation of zero field splittings (or
      magnetic anisotropies) of multinuclear transition metal complexes is further
      developed. A procedure is suggested how to extract spin Hamiltonian parameters
      for anisotropic exchange from a set of broken symmetry density functional
      calculations. For isotropic exchange coupling constants Jij, the established
      procedure is retrieved, and anisotropic (or pseudodipolar) exchange coupling
      tensors Dij are obtained analogously. This procedure only yields the sum of the
      individual single-ion zero field splitting tensors Di. Therefore, a procedure
      based on localized orbitals has been developed to extract the individual single
      ion contributions. With spin Hamiltonian parameters at hand, the zero field
      splittings of the individual spin multiplets are calculated by an exact
      diagonalization of the isotropic part, followed by a spin projection done
      numerically. The method is applied to the binuclear cation [LCr(OH)3CrL](3 +) (L
      = 1,4,7-trimethyl-1,4,7-triazanonane) for which experimental zero field
      splittings for all low-energy spin states are known, and to the single-molecule
      magnet [Fe4(CH3C(CH2O)3)2(dpm)6] (Hdpm = 2,2,6,6-tetramethylheptane-3,5-dione).
      In both these 3d compounds, the single-ion tensors mainly come from the spin
      orbit interaction. Anisotropic exchange is dominated by the spin-dipolar
      interaction only for the chromium compound. Despite the rather small isotropic
      exchange couplings in the iron compound, spin-orbit and spin-dipolar
      contributions to anisotropic exchange are of similar size here. 

PMID- 24320258
TI  - Shortcomings of the standard Lennard-Jones dispersion term in water models,
      studied with force matching.
AB  - In this work, ab initio parametrization of water force field is used to get
      insights into the functional form of empirical potentials to properly model the
      physics underlying dispersion interactions. We exploited the force matching
      algorithm to fit the interaction forces obtained with dispersion corrected
      density functional theory based molecular dynamics simulations. We found that the
      standard Lennard-Jones interaction potentials poorly reproduce the attractive
      character of dispersion forces. This drawback can be resolved by accounting for
      the distinctive short range behavior of dispersion interactions, multiplying the
      r(-6) term by a damping function. We propose two novel parametrizations of the
      force field using different damping functions. Structural and dynamical
      properties of the new models are computed and compared with the ones obtained
      from the non-damped force field, showing an improved agreement with reference
      first principle calculations. 

PMID- 24320259
TI  - Efficient calculation of many-body induced electrostatics in molecular systems.
AB  - Potential energy functions including many-body polarization are in widespread use
      in simulations of aqueous and biological systems, metal-organics, molecular
      clusters, and other systems where electronically induced redistribution of charge
      among local atomic sites is of importance. The polarization interactions, treated
      here via the methods of Thole and Applequist, while long-ranged, can be computed
      for moderate-sized periodic systems with extremely high accuracy by extending
      Ewald summation to the induced fields as demonstrated by Nymand, Sala, and
      others. These full Ewald polarization calculations, however, are expensive and
      often limited to very small systems, particularly in Monte Carlo simulations,
      which may require energy evaluation over several hundred-thousand configurations.
      For such situations, it shall be shown that sufficiently accurate computation of
      the polarization energy can be produced in a fraction of the central processing
      unit (CPU) time by neglecting the long-range extension to the induced fields
      while applying the long-range treatments of Ewald or Wolf to the static fields;
      these methods, denoted Ewald E-Static and Wolf E-Static (WES), respectively,
      provide an effective means to obtain polarization energies for intermediate and
      large systems including those with several thousand polarizable sites in a
      fraction of the CPU time. Furthermore, we shall demonstrate a means to optimize
      the damping for WES calculations via extrapolation from smaller trial systems. 

PMID- 24320260
TI  - N-body:Many-body QM:QM vibrational frequencies: application to small hydrogen
      bonded clusters.
AB  - We present an efficient method for reproducing CCSD(T) (i.e., the coupled-cluster
      method with single, double and perturbative connected triple excitations)
      optimized geometries and harmonic vibrational frequencies for molecular clusters
      with the N-body:Many-body QM:QM technique. In this work, all 1-body through N
      body interactions are obtained from CCSD(T) computations, and the higher-order
      interactions are captured at the MP2 level. The linear expressions from the many
      body expansion facilitate a straightforward evaluation of geometrical derivative
      properties (e.g., gradients and Hessians). For (H2O)n clusters (n = 3-7),
      optimized structures obtained with the 2-body:Many-body CCSD(T):MP2 method are
      virtually identical to CCSD(T) optimized geometries. Harmonic vibrational
      frequencies calculated with this 2-body:Many-body approach differ from CCSD(T)
      frequencies by at most a few cm(-1). These deviations can be systematically
      reduced by including more terms from the many-body expansion at the CCSD(T)
      level. Maximum deviations between CCSD(T) and 3-body:Many-body CCSD(T):MP2
      frequencies are typically only a few tenths of a cm(-1) for the H2O clusters
      examined in this work. These results are obtained at a fraction of the wall time
      of the supermolecular CCSD(T) computation, and the approach is well-suited for
      parallelization on relatively modest computational hardware. 

PMID- 24320261
TI  - Projected and hidden Markov models for calculating kinetics and metastable states
      of complex molecules.
AB  - Markov state models (MSMs) have been successful in computing metastable states,
      slow relaxation timescales and associated structural changes, and stationary or
      kinetic experimental observables of complex molecules from large amounts of
      molecular dynamics simulation data. However, MSMs approximate the true dynamics
      by assuming a Markov chain on a clusters discretization of the state space. This
      approximation is difficult to make for high-dimensional biomolecular systems, and
      the quality and reproducibility of MSMs has, therefore, been limited. Here, we
      discard the assumption that dynamics are Markovian on the discrete clusters.
      Instead, we only assume that the full phase-space molecular dynamics is
      Markovian, and a projection of this full dynamics is observed on the discrete
      states, leading to the concept of Projected Markov Models (PMMs). Robust
      estimation methods for PMMs are not yet available, but we derive a practically
      feasible approximation via Hidden Markov Models (HMMs). It is shown how various
      molecular observables of interest that are often computed from MSMs can be
      computed from HMMs/PMMs. The new framework is applicable to both, simulation and
      single-molecule experimental data. We demonstrate its versatility by applications
      to educative model systems, a 1 ms Anton MD simulation of the bovine pancreatic
      trypsin inhibitor protein, and an optical tweezer force probe trajectory of an
      RNA hairpin. 

PMID- 24320262
TI  - A new post-quantization constrained propagator for rigid tops for use in path
      integral quantum simulations.
AB  - In this paper, we extend the previously introduced Post-Quantization Constraints
      (PQC) procedure [G. Guillon, T. Zeng, and P.-N. Roy, J. Chem. Phys. 138, 184101
      (2013)] to construct approximate propagators and energy estimators for different
      rigid body systems, namely, the spherical, symmetric, and asymmetric tops. These
      propagators are for use in Path Integral simulations. A thorough discussion of
      the underlying geometrical concepts is given. Furthermore, a detailed analysis of
      the convergence properties of the density as well as the energy estimators
      towards their exact counterparts is presented along with illustrative numerical
      examples. The Post-Quantization Constraints approach can yield converged results
      and is a practical alternative to so-called sum over states techniques, where one
      has to expand the propagator as a sum over a complete set of rotational
      stationary states [as in E. G. Noya, C. Vega, and C. McBride, J. Chem. Phys. 134,
      054117 (2011)] because of its modest memory requirements. 

PMID- 24320263
TI  - Extreme density-driven delocalization error for a model solvated-electron system.
AB  - Delocalization (or charge-transfer) error is one of the scarce but spectacular
      failures of density-functional theory. It is particularly apparent in extensively
      delocalized molecules, and manifests in the calculation of bandgaps, reaction
      barriers, and dissociation limits. Even though delocalization error is always
      present in the self-consistent electron density, the differences from reference
      densities are often quite subtle and the error tends to be driven by the exchange
      correlation energy expression. In this article, we propose a model system (the
      Kevan model) where approximate density functionals predict dramatically different
      charge distributions because of delocalization error. The model system consists
      of an electron trapped in a water hexamer and is a finite representation of an
      experimentally observed class of solids: electrides. The Kevan model is of
      fundamental interest because it allows the estimation of charge transfer error
      without recourse to fractional charge calculations, but our results are also
      relevant in the context of the modeling of confined electrons in density
      functional theory. 

PMID- 24320264
TI  - Molecular electrostatic potentials by systematic molecular fragmentation.
AB  - A simple method is presented for estimating the molecular electrostatic potential
      in and around molecules using systematic molecular fragmentation. This approach
      estimates the potential directly from the electron density. The accuracy of the
      method is established for a set of organic molecules and ions. The utility of the
      approach is demonstrated by estimating the binding energy of a water molecule in
      an internal cavity in the protein ubiquitin. 

PMID- 24320265
TI  - Metrics for measuring distances in configuration spaces.
AB  - In order to characterize molecular structures we introduce configurational
      fingerprint vectors which are counterparts of quantities used experimentally to
      identify structures. The Euclidean distance between the configurational
      fingerprint vectors satisfies the properties of a metric and can therefore safely
      be used to measure dissimilarities between configurations in the high dimensional
      configuration space. In particular we show that these metrics are a perfect and
      computationally cheap replacement for the root-mean-square distance (RMSD) when
      one has to decide whether two noise contaminated configurations are identical or
      not. We introduce a Monte Carlo approach to obtain the global minimum of the RMSD
      between configurations, which is obtained from a global minimization over all
      translations, rotations, and permutations of atomic indices. 

PMID- 24320266
TI  - The critical compressibility factor of fluids from the global isomorphism
      approach.
AB  - The relation between the critical compressibility factors Zc of the Lennard-Jones
      fluid and the Lattice Gas (Ising model) is derived within the global isomorphism
      approach. On this basis, we obtain the alternative form for the value of the
      critical compressibility factor which is different from widely used
      phenomenological Timmermans relation. The estimates for the critical pressure Pc
      and Zc of the Lennard-Jones fluid are obtained in case of two and three
      dimensions. The extension of the formalism is proposed to include the Pitzer's
      acentric factor into consideration. 

PMID- 24320267
TI  - Enhanced sensitivity in H photofragment detection by two-color reduced-Doppler
      ion imaging.
AB  - Two-color reduced-Doppler (TCRD) and one-color velocity map imaging (VMI) were
      used for probing H atom photofragments resulting from the ~243.1 nm
      photodissociation of pyrrole. The velocity components of the H photofragments
      were probed by employing two counterpropagating beams at close and fixed
      wavelengths of 243.15 and 243.12 nm in TCRD and a single beam at ~243.1 nm,
      scanned across the Doppler profile in VMI. The TCRD imaging enabled probing of
      the entire velocity distribution in a single pulse, resulting in enhanced
      ionization efficiency, as well as improved sensitivity and signal-to-noise ratio.
      These advantages were utilized for studying the pyrrole photodissociation at
      ~243.1 and 225 nm, where the latter wavelength provided only a slight increase in
      the H yield over the self-signal from the probe beams. The TCRD imaging enabled
      obtaining high quality H(+) images, even for the low H photofragment yields
      formed in the 225 nm photolysis process, and allowed determining the velocity
      distributions and anisotropy parameters and getting insight into pyrrole
      photodissociation.

PMID- 24320268
TI  - Electron impact excitation of the low-lying 3s[3/2]1 and 3s'[1/2]1 levels in neon
      for incident energies between 20 and 300 eV.
AB  - Absolute differential cross sections (DCSs) for electron impact of the two lower
      lying 3s[3/2]1 ((3)P0) and 3s(')[1/2]1 ((1)P1) electronic states in neon (Ne)
      have been determined for eight incident electron energies in the range 20-300 eV.
      Comparisons between our results and previous measurements and calculations, where
      possible, are provided with best agreement being found with the recent large
      scale B-spline R-matrix computations [O. Zatsarinny and K. Bartschat, Phys. Rev.
      A 86, 022717 (2012)]. Based on these DCSs at 100, 200, and 300 eV, a generalised
      oscillator strength analysis enabled us to determine estimates for the optical
      oscillator strengths of the 3s[3/2]1 and 3s(')[1/2]1 levels. In this case,
      excellent agreement was found with a range of independent experiments and
      calculations, giving us some confidence in the validity of our measurement and
      analysis procedures. Integral cross sections, derived from the present DCSs, were
      presented graphically and discussed elsewhere [M. Hoshino, H. Murai, H. Kato, Y.
      Itikawa, M. J. Brunger, and H. Tanaka, Chem. Phys. Lett. 585, 33 (2013)], but are
      tabulated here for completeness. 

PMID- 24320269
TI  - Full dimensional potential energy surface for the ground state of H4(+) system
      based on triatomic-in-molecules formalism.
AB  - In this work, we present a global potential energy surface for the ground
      electronic state of the H4(+) based on ab initio calculations. The final fit is
      based on triatomics-in-molecules (TRIM) approximation and it includes extra four
      body terms for the better description of some discrepancies found on the TRIM
      model. The TRIM method itself allows a very accurate description of the
      asymptotic regions. The global fit uses more than 19,000 multireference
      configuration interaction ab initio points. The global potential energy surface
      has an overall root mean square error of 0.013 eV for energies up to 2 eV above
      the global minimum. This work presents an analysis of the stationary points,
      reactant and product channels, and crossing between the two lowest TRIM adiabatic
      states. It is as well included a brief description of the two first excited
      states of the TRIM matrix, concluding that TRIM method is a very good
      approximation not only for the ground state but also for at least two of the
      excited states of H4(+) system.

PMID- 24320270
TI  - Interaction of TiO2(-) with water: photoelectron spectroscopy and density
      functional calculations.
AB  - The interactions of titania with water molecules were studied via photoelectron
      spectroscopy and density functional calculations of TiO(OH)2(-) and
      Ti(OH)4(H2O)n(-) (n = 0-5) clusters which are corresponding to the TiO2(H2O)(-)
      and TiO2(H2O)n+2(-) (n = 0-5) systems, respectively. Experimental observation and
      theoretical calculations confirmed that TiO(OH)2(-) was produced when TiO2(-)
      interacts with one water molecule, and Ti(OH)4(H2O)n(-) (n = 0-5) were produced
      successively when TiO2(-) interacts with two or more water molecules. The
      structures of Ti(OH)4(H2O)n(-) with n = 4, 5 are slightly different from those of
      n = 1-3. The structures of Ti(OH)4(H2O)1-3(-) can be viewed as the water
      molecules interacting with the Ti(OH)4(-) core through hydrogen bonds; however,
      in Ti(OH)4(H2O)4,5(-), one of the water molecules interacts directly with the Ti
      atom via its oxygen atom instead of a hydrogen bond and distorted the Ti(OH)4(-)
      core.

PMID- 24320271
TI  - Ionization photophysics and spectroscopy of dicyanoacetylene.
AB  - Photoionization of dicyanoacetylene was studied using synchrotron radiation over
      the excitation range 8-25 eV, with photoelectron-photoion coincidence techniques.
      The absolute ionization cross-section and detailed spectroscopic aspects of the
      parent ion were recorded. The adiabatic ionization energy of dicyanoacetylene was
      measured as 11.80 +/- 0.01 eV. A detailed analysis of the cation spectroscopy
      involves new aspects and new assignments of the vibrational components to
      excitation of the quasi-degenerate A(2)Pig, B(2)Sigmag(+) states as well as the
      C(2)Sigmau(+) and D(2)Piu states of the cation. Some of the structured
      autoionization features observed in the 12.4-15 eV region of the total ion yield
      spectrum were assigned to vibrational components of valence shell transitions and
      to two previously unknown Rydberg series converging to the D(2)Piu state of
      C4N2(+). The appearance energies of the fragment ions C4N(+), C3N(+), C4(+),
      C2N(+), and C2(+) were measured and their heats of formation were determined and
      compared with existing literature values. Thermochemical calculations of the
      appearance potentials of these and other weaker ions were used to infer aspects
      of dissociative ionization pathways.

PMID- 24320272
TI  - Electron attachment to indole and related molecules.
AB  - Gas-phase formation of temporary negative ion states via resonance attachment of
      low-energy (0-6 eV) electrons into vacant molecular orbitals of indoline (I),
      indene (II), indole (III), 2-methylen-1,3,3-trimethylindoline (IV), and 2,3,3
      trimethyl-indolenine (V) was investigated for the first time by electron
      transmission spectroscopy (ETS). The description of their empty-level structures
      was supported by density functional theory and Hartree-Fock calculations, using
      empirically calibrated linear equations to scale the calculated virtual orbital
      energies. Dissociative electron attachment spectroscopy (DEAS) was used to
      measure the fragment anion yields generated through dissociative decay channels
      of the parent molecular anions of compounds I-V, detected with a mass filter as a
      function of the incident electron energy in the 0-14 eV energy range. The
      vertical and adiabatic electron affinities were evaluated at the B3LYP/6-31+G(d)
      level as the anion/neutral total energy difference. The same theoretical method
      is also used for evaluation of the thermodynamic energy thresholds for production
      of the negative fragments observed in the DEA spectra. The loss of a hydrogen
      atom from the parent molecular anion ([M-H](-)) provides the most intense signal
      in compounds I-IV. The gas-phase DEAS data can provide support for biochemical
      reaction mechanisms in vivo involving initial hydrogen abstraction from the
      nitrogen atom of the indole moiety, present in a variety of biologically
      important molecules. 

PMID- 24320273
TI  - Electron attachment to C2 fluorocarbon radicals at high temperature.
AB  - Thermal electron attachment to the radical species C2F3 and C2F5 has been studied
      over the temperature range 300-890 K using the Variable Electron and Neutral
      Density Attachment Mass Spectrometry technique. Both radicals exclusively undergo
      dissociative attachment to yield F(-). The rate constant for C2F5 shows little
      dependence over the temperature range, remaining ~4 * 10(-9) cm(3) s(-1). The
      rate constant for C2F3 attachment rises steeply with temperature from 3 * 10(-11)
      cm(3) s(-1) at 300 K to 1 * 10(-9) cm(3) s(-1) at 890 K. The behaviors of both
      species at high temperature are in agreement with extrapolations previously made
      from data below 600 K using a recently developed kinetic modeling approach.
      Measurements were also made on C2F3Br and C2F5Br (used in this work as precursors
      to the radicals) over the same temperature range, and, for C2F5Br as a function
      of electron temperature. The attachment rate constants to both species rise with
      temperature following Arrhenius behavior. The attachment rate constant to C2F5Br
      falls with increasing electron temperature, in agreement with the kinetic
      modeling. The current data fall in line with past predictions of the kinetic
      modeling approach, again showing the utility of this simplified approach.

PMID- 24320274
TI  - Energy level alignment and quantum conductance of functionalized metal-molecule
      junctions: density functional theory versus GW calculations.
AB  - We study the effect of functional groups (CH3*4, OCH3, CH3, Cl, CN, F*4) on the
      electronic transport properties of 1,4-benzenediamine molecular junctions using
      the non-equilibrium Green function method. Exchange and correlation effects are
      included at various levels of theory, namely density functional theory (DFT),
      energy level-corrected DFT (DFT+Sigma), Hartree-Fock and the many-body GW
      approximation. All methods reproduce the expected trends for the energy of the
      frontier orbitals according to the electron donating or withdrawing character of
      the substituent group. However, only the GW method predicts the correct ordering
      of the conductance amongst the molecules. The absolute GW (DFT) conductance is
      within a factor of two (three) of the experimental values. Correcting the DFT
      orbital energies by a simple physically motivated scissors operator, Sigma, can
      bring the DFT conductances close to experiments, but does not improve on the
      relative ordering. We ascribe this to a too strong pinning of the molecular
      energy levels to the metal Fermi level by DFT which suppresses the variation in
      orbital energy with functional group. 

PMID- 24320275
TI  - Assessment of charge-transfer excitations with time-dependent, range-separated
      density functional theory based on long-range MP2 and multiconfigurational self
      consistent field wave functions.
AB  - Charge transfer excitations can be described within Time-Dependent Density
      Functional Theory (TD-DFT), not only by means of the Coulomb Attenuated Method
      (CAM) but also with a combination of wave function theory and TD-DFT based on
      range separation. The latter approach enables a rigorous formulation of multi
      determinantal TD-DFT schemes where excitation classes, which are absent in
      conventional TD-DFT spectra (like for example double excitations), can be
      addressed. This paper investigates the combination of both the long-range Multi
      Configuration Self-Consistent Field (MCSCF) and Second Order Polarization
      Propagator Approximation (SOPPA) ansatze with a short-range DFT (srDFT)
      description. We find that the combinations of SOPPA or MCSCF with TD-DFT yield
      better results than could be expected from the pure wave function schemes. For
      the Time-Dependent MCSCF short-range DFT ansatz (TD-MC-srDFT) excitation energies
      calculated over a larger benchmark set of molecules with predominantly single
      reference character yield good agreement with their reference values, and are in
      general comparable to the CAM-B3LYP functional. The SOPPA-srDFT scheme is tested
      for a subset of molecules used for benchmarking TD-MC-srDFT and performs slightly
      better against the reference data for this small subset. Beyond the proof-of
      principle calculations comprising the first part of this contribution, we
      additionally studied the low-lying singlet excited states (S1 and S2) of the
      retinal chromophore. The chromophore displays multireference character in the
      ground state and both excited states exhibit considerable double excitation
      character, which in turn cannot be described within standard TD-DFT, due to the
      adiabatic approximation. However, a TD-MC-srDFT approach can account for the
      multireference character, and excitation energies are obtained with accuracy
      comparable to CASPT2, although using a much smaller active space. 

PMID- 24320276
TI  - Enhancement of strong-field multiple ionization in the vicinity of the conical
      intersection in 1,3-cyclohexadiene ring opening.
AB  - Nonradiative energy dissipation in electronically excited polyatomic molecules
      proceeds through conical intersections, loci of degeneracy between electronic
      states. We observe a marked enhancement of laser-induced double ionization in the
      vicinity of a conical intersection during a non-radiative transition. We measured
      double ionization by detecting the kinetic energy of ions released by laser
      induced strong-field fragmentation during the ring-opening transition between 1,3
      cyclohexadiene and 1,3,5-hexatriene. The enhancement of the double ionization
      correlates with the conical intersection between the HOMO and LUMO orbitals. 

PMID- 24320277
TI  - An investigation into electron scattering from pyrazine at intermediate and high
      energies.
AB  - Total electron scattering cross sections for pyrazine in the energy range 10-500
      eV have been measured with a new magnetically confined electron transmission-beam
      apparatus. Theoretical differential and integral elastic, as well as integral
      inelastic, cross sections have been calculated by means of a screening-corrected
      form of the independent-atom representation (IAM-SCAR) from 10 to 1000 eV
      incident electron energies. The present experimental and theoretical total cross
      sections show a good level of agreement, to within 10%, in the overlapping energy
      range. Consistency of these results with previous calculations (i.e., the R
      matrix and Schwinger Multichannel methods) and elastic scattering measurements at
      lower energies, below 10 eV, is also discussed. 

PMID- 24320278
TI  - Competition of the connectivity with the local and the global order in polymer
      melts and crystals.
AB  - The competition between the connectivity and the local or global order in model
      fully flexible chain molecules is investigated by molecular-dynamics simulations.
      States with both missing (melts) and high (crystal) global order are considered.
      Local order is characterized within the first coordination shell (FCS) of a
      tagged monomer and found to be lower than in atomic systems in both melt and
      crystal. The role played by the bonds linking the tagged monomer to FCS monomers
      (radial bonds), and the bonds linking two FCS monomers (shell bonds) is
      investigated. The detailed analysis in terms of Steinhardt's orientation order
      parameters Ql (l = 2 - 10) reveals that increasing the number of shell bonds
      decreases the FCS order in both melt and crystal. Differently, the FCS
      arrangements organize the radial bonds. Even if the molecular chains are fully
      flexible, the distribution of the angle formed by adjacent radial bonds exhibits
      sharp contributions at the characteristic angles theta ~ 70 degrees , 122 degrees
      , 180 degrees . The fractions of adjacent radial bonds with theta ~ 122 degrees ,
      180 degrees  are enhanced by the global order of the crystal, whereas the
      fraction with 70 degrees  ~/< theta ~/< 110 degrees  is nearly unaffected by the
      crystallization. Kink defects, i.e., large lateral displacements of the chains,
      are evidenced in the crystalline state.

PMID- 24320279
TI  - Spatiotemporal heterogeneity of local free volumes in highly supercooled liquid.
AB  - We discuss the spatiotemporal behavior of local density and its relation to
      dynamical heterogeneity in a highly supercooled liquid by using molecular
      dynamics simulations of a binary mixture with different particle sizes in two
      dimensions. To trace voids heterogeneously existing with lower local densities,
      which move along with the structural relaxation, we employ the minimum local
      density for each particle in a time window whose width is set along with the
      structural relaxation time. Particles subject to free volumes correspond well to
      the configuration rearranging region of dynamical heterogeneity. While the
      correlation length for dynamical heterogeneity grows with temperature decrease,
      no growth in the correlation length of heterogeneity in the minimum local density
      distribution takes place. A comparison of these results with those of normal mode
      analysis reveals that superpositions of lower-frequency soft modes extending over
      the free volumes exhibit spatial correlation with the broken bonds. This
      observation suggests a possibility that long-ranged vibration modes facilitate
      the interactions between fragile regions represented by free volumes, to induce
      dynamical correlations at a large scale. 

PMID- 24320280
TI  - Analytical equation of state with three-body forces: application to noble gases.
AB  - We developed an explicit equation of state (EOS) for small non polar molecules by
      means of an effective two-body potential. The average effect of three-body forces
      was incorporated as a perturbation, which results in rescaled values for the
      parameters of the two-body potential. These values replace the original ones in
      the EOS corresponding to the two-body interaction. We applied this procedure to
      the heavier noble gases and used a modified Kihara function with an effective
      Axilrod-Teller-Muto (ATM) term to represent the two- and three-body forces. We
      also performed molecular dynamics simulations with two- and three-body forces.
      There was good agreement between predicted, simulated, and experimental
      thermodynamic properties of neon, argon, krypton, and xenon, up to twice the
      critical density and up to five times the critical temperature. In order to
      achieve 1% accuracy of the pressure at liquid densities, the EOS must incorporate
      the effect of ATM forces. The ATM factor in the rescaled two-body energy is most
      important at temperatures around and lower than the critical one. Nonetheless,
      the rescaling of two-body diameter cannot be neglected at liquid-like densities
      even at high temperature. This methodology can be extended straightforwardly to
      deal with other two- and three-body potentials. It could also be used for other
      nonpolar substances where a spherical two-body potential is still a reasonable
      coarse-grain approximation. 

PMID- 24320281
TI  - Pressure-induced transformations in computer simulations of glassy water.
AB  - Glassy water occurs in at least two broad categories: low-density amorphous (LDA)
      and high-density amorphous (HDA) solid water. We perform out-of-equilibrium
      molecular dynamics simulations to study the transformations of glassy water using
      the ST2 model. Specifically, we study the known (i) compression-induced LDA-to
      HDA, (ii) decompression-induced HDA-to-LDA, and (iii) compression-induced
      hexagonal ice-to-HDA transformations. We study each transformation for a broad
      range of compression/decompression temperatures, enabling us to construct a "P-T
      phase diagram" for glassy water. The resulting phase diagram shows the same
      qualitative features reported from experiments. While many simulations have
      probed the liquid-state phase behavior, comparatively little work has examined
      the transitions of glassy water. We examine how the glass transformations relate
      to the (first-order) liquid-liquid phase transition previously reported for this
      model. Specifically, our results support the hypothesis that the liquid-liquid
      spinodal lines, between a low-density and high-density liquid, are extensions of
      the LDA-HDA transformation lines in the limit of slow compression. Extending
      decompression runs to negative pressures, we locate the sublimation lines for
      both LDA and hyperquenched glassy water (HGW), and find that HGW is relatively
      more stable to the vapor. Additionally, we observe spontaneous crystallization of
      HDA at high pressure to ice VII. Experiments have also seen crystallization of
      HDA, but to ice XII. Finally, we contrast the structure of LDA and HDA for the
      ST2 model with experiments. We find that while the radial distribution functions
      (RDFs) of LDA are similar to those observed in experiments, considerable
      differences exist between the HDA RDFs of ST2 water and experiment. The
      differences in HDA structure, as well as the formation of ice VII (a tetrahedral
      crystal), are a consequence of ST2 overemphasizing the tetrahedral character of
      water. 

PMID- 24320282
TI  - Computer simulation of liquid-vapor coexistence of confined quantum fluids.
AB  - The liquid-vapor coexistence (LV) of bulk and confined quantum fluids has been
      studied by Monte Carlo computer simulation for particles interacting via a
      semiclassical effective pair potential Veff(r) = VLJ + VQ, where VLJ is the
      Lennard-Jones 12-6 potential (LJ) and VQ is the first-order Wigner-Kirkwood (WK
      1) quantum potential, that depends on beta = 1/kT and de Boer's quantumness
      parameter Lambda=h/sigma?mepsilon, where k and h are the Boltzmann's and Planck's
      constants, respectively, m is the particle's mass, T is the temperature of the
      system, and sigma and epsilon are the LJ potential parameters. The non-conformal
      properties of the system of particles interacting via the effective pair
      potential Veff(r) are due to Lambda, since the LV phase diagram is modified by
      varying Lambda. We found that the WK-1 system gives an accurate description of
      the LV coexistence for bulk phases of several quantum fluids, obtained by the
      Gibbs Ensemble Monte Carlo method (GEMC). Confinement effects were introduced
      using the Canonical Ensemble (NVT) to simulate quantum fluids contained within
      parallel hard walls separated by a distance Lp, within the range 2sigma <= Lp <=
      6sigma. The critical temperature of the system is reduced by decreasing Lp and
      increasing Lambda, and the liquid-vapor transition is not longer observed for
      Lp/sigma < 2, in contrast to what has been observed for the classical system.

PMID- 24320283
TI  - Statistical mechanics of Roskilde liquids: configurational adiabats, specific
      heat contours, and density dependence of the scaling exponent.
AB  - We derive exact results for the rate of change of thermodynamic quantities, in
      particular, the configurational specific heat at constant volume, CV, along
      configurational adiabats (curves of constant excess entropy Sex). Such curves are
      designated isomorphs for so-called Roskilde liquids, in view of the invariance of
      various structural and dynamical quantities along them. The slope of the
      isomorphs in a double logarithmic representation of the density-temperature phase
      diagram, gamma, can be interpreted as one third of an effective inverse power-law
      potential exponent. We show that in liquids where gamma increases (decreases)
      with density, the contours of CV have smaller (larger) slope than configurational
      adiabats. We clarify also the connection between gamma and the pair potential. A
      fluctuation formula for the slope of the CV-contours is derived. The theoretical
      results are supported with data from computer simulations of two systems, the
      Lennard-Jones fluid, and the Girifalco fluid. The sign of dgamma/drho is thus a
      third key parameter in characterizing Roskilde liquids, after gamma and the
      virial-potential energy correlation coefficient R. To go beyond isomorph theory
      we compare invariance of a dynamical quantity, the self-diffusion coefficient,
      along adiabats and CV-contours, finding it more invariant along adiabats. 

PMID- 24320284
TI  - Shear propagation in the terahertz dynamics of water-glycerol mixtures.
AB  - Inelastic X-ray and neutron scattering techniques were jointly used to
      investigate the dynamics of water-glycerol mixtures at different concentrations
      and temperatures. It was observed that even relatively low concentrations of
      glycerol increase the damping of shear modes, as a consequence of the known
      ability of glycerol to disrupt the hydrogen bond network of water. A similar
      trend was observed when increasing the temperature, which suggests the presence
      of a locus in the concentration-temperature plane marking a crossover in the
      shear modulus. 

PMID- 24320285
TI  - Identifying Dirac cones in carbon allotropes with square symmetry.
AB  - A theoretical study is conducted to search for Dirac cones in two-dimensional
      carbon allotropes with square symmetry. By enumerating the carbon atoms in a unit
      cell up to 12, an allotrope with octatomic rings is recognized to possess Dirac
      cones under a simple tight-binding approach. The obtained Dirac cones are
      accompanied by flat bands at the Fermi level, and the resulting massless Dirac
      Weyl fermions are chiral particles with a pseudospin of S = 1, rather than the
      conventional S = 1/2 of graphene. The spin-1 Dirac cones are also predicted to
      exist in hexagonal graphene antidot lattices. 

PMID- 24320286
TI  - Electric force microscopy of semiconductors: theory of cantilever frequency
      fluctuations and noncontact friction.
AB  - An electric force microscope employs a charged atomic force microscope probe in
      vacuum to measure fluctuating electric forces above the sample surface generated
      by dynamics of molecules and charge carriers. We present a theoretical
      description of two observables in electric force microscopy of a semiconductor:
      the spectral density of cantilever frequency fluctuations (jitter), which are
      associated with low-frequency dynamics in the sample, and the coefficient of
      noncontact friction, induced by higher-frequency motions. The treatment is
      classical-mechanical, based on linear response theory and classical
      electrodynamics of diffusing charges in a dielectric continuum. Calculations of
      frequency jitter explain the absence of contributions from carrier dynamics to
      previous measurements of an organic field effect transistor. Calculations of
      noncontact friction predict decreasing friction with increasing carrier density
      through the suppression of carrier density fluctuations by intercarrier Coulomb
      interactions. The predicted carrier density dependence of the friction
      coefficient is consistent with measurements of the dopant density dependence of
      noncontact friction over Si. Our calculations predict that in contrast to the
      measurement of cantilever frequency jitter, a noncontact friction measurement
      over an organic semiconductor could show appreciable contributions from charge
      carriers. 

PMID- 24320287
TI  - Repulsive interactions of a lipid membrane with graphene in composite materials.
AB  - The van der Waals interaction between a lipid membrane and a substrate covered by
      a graphene sheet is investigated using the Lifshitz theory. The reflection
      coefficients are obtained for a layered planar system submerged in water. The
      dielectric response properties of the involved materials are also specified and
      discussed. Our calculations show that a graphene covered substrate can repel the
      biological membrane in water. This is attributed to the significant changes in
      the response properties of the system due to the monolayer graphene. It is also
      found that the van der Waals interaction is mostly dominated by the presence of
      graphene, while the role of the particular substrate is secondary. 

PMID- 24320288
TI  - Transversal thermal transport in single-walled carbon nanotube bundles: influence
      of axial stretching and intertube bonding.
AB  - Using reverse nonequilibrium molecular dynamics simulations the influence of
      intermolecular bridges on the thermal conductivity (lambda) in carbon nanotube
      (CNT) bundles has been investigated. The chosen cross linkers (CH2, O, CO)
      strengthen the transversal energy transport relative to the one in CNT bundles
      without bridges. The results showed that lambda does not increase linearly with
      the linker density. The efficiency of the heat transport is determined by the
      number of linkers in the direction of the heat flux, the type of the linker, and
      their spatial ordering. The influence of a forced axial stress on the transversal
      lambda has been also studied. The observed lambda reduction with increasing axial
      stretching in a neat CNT bundle can be (over)compensated by cross linkers. The
      present computational data emphasize the contribution of phonons to the
      transversal heat transport in CNT bundles with intertube bonds. 

PMID- 24320289
TI  - Six-dimensional quantum dynamics study for the dissociative adsorption of HCl on
      Au(111) surface.
AB  - The six-dimensional quantum dynamics calculations for the dissociative
      chemisorption of HCl on Au(111) are carried out using the time-dependent wave
      packet approach, based on an accurate PES which was recently developed by neural
      network fitting to density functional theory energy points. The influence of
      vibrational excitation and rotational orientation of HCl on the reactivity is
      investigated by calculating the exact six-dimensional dissociation probabilities,
      as well as the four-dimensional fixed-site dissociation probabilities. The
      vibrational excitation of HCl enhances the reactivity and the helicopter
      orientation yields higher dissociation probability than the cartwheel
      orientation. A new interesting site-averaged effect is found for the title
      molecule-surface system that one can essentially reproduce the six-dimensional
      dissociation probability by averaging the four-dimensional dissociation
      probabilities over 25 fixed sites. 

PMID- 24320290
TI  - Near-edge band structures and band gaps of Cu-based semiconductors predicted by
      the modified Becke-Johnson potential plus an on-site Coulomb U.
AB  - Diamond-like Cu-based multinary semiconductors are a rich family of materials
      that hold promise in a wide range of applications. Unfortunately, accurate
      theoretical understanding of the electronic properties of these materials is
      hindered by the involvement of Cu d electrons. Density functional theory (DFT)
      based calculations using the local density approximation or generalized gradient
      approximation often give qualitative wrong electronic properties of these
      materials, especially for narrow-gap systems. The modified Becke-Johnson (mBJ)
      method has been shown to be a promising alternative to more elaborate theory such
      as the GW approximation for fast materials screening and predictions. However,
      straightforward applications of the mBJ method to these materials still encounter
      significant difficulties because of the insufficient treatment of the localized d
      electrons. We show that combining the promise of mBJ potential and the spirit of
      the well-established DFT + U method leads to a much improved description of the
      electronic structures, including the most challenging narrow-gap systems. A
      survey of the band gaps of about 20 Cu-based semiconductors calculated using the
      mBJ + U method shows that the results agree with reliable values to within +/-0.2
      eV. 

PMID- 24320291
TI  - Orbital dependent Rashba splitting and electron-phonon coupling of 2D Bi phase on
      Cu(100) surface.
AB  - A monolayer of bismuth deposited on the Cu(100) surface forms a highly ordered
      c(2*2) reconstructed phase. The low energy single particle excitations of the
      c(2*2) Bi/Cu(100) present Bi-induced states with a parabolic dispersion in the
      energy region close to the Fermi level, as observed by angle-resolved
      photoemission spectroscopy. The electronic state dispersion, the charge density
      localization, and the spin-orbit coupling have been investigated combining
      photoemission spectroscopy and density functional theory, unraveling a two
      dimensional Bi phase with charge density well localized at the interface. The Bi
      induced states present a Rashba splitting, when the charge density is strongly
      localized in the Bi plane. Furthermore, the temperature dependence of the
      spectral density close to the Fermi level has been evaluated. Dispersive
      electronic states offer a large number of decay channels for transitions coupled
      to phonons and the strength of the electron-phonon coupling for the Bi/Cu(100)
      system is shown to be stronger than for Bi surfaces and to depend on the
      electronic state symmetry and localization.

PMID- 24320292
TI  - Non-dissociative activation of chemisorbed dinitrogen on Ni{110} by co-adsorbed
      lithium.
AB  - Weakening the intramolecular N-N bond is essential to promote direct
      hydrogenation of adsorbed N2 on catalyst surfaces. The interaction of N2 with Li
      on Ni{110} surfaces has been investigated. We show that the N-N bond is
      significantly weakened with increasing Li coverage, evidenced by large redshifts
      in N-N stretch frequency of up to 380 cm(-1) compared to the gas phase. Some
      increased thermal stability of the most weakened N2,ads states is also observed.
      We speculate that the various observed redshifts in N-N stretch frequency are
      associated with an enhanced backfilling of the 2pi* antibonding orbital of N2 due
      to both the Li-induced surface electrostatic field, and the formation of Lix(N2)y
      surface complexes.

PMID- 24320293
TI  - Temperature effect on the small-to-large crossover lengthscale of hydrophobic
      hydration.
AB  - The thermodynamics of hydration is expected to change gradually from entropic for
      small solutes to enthalpic for large ones. The small-to-large crossover
      lengthscale of hydrophobic hydration depends on the thermodynamic conditions of
      the solvent such as temperature, pressure, presence of additives, etc. We attempt
      to shed some light on the temperature dependence of the crossover lengthscale by
      using a probabilistic approach to water hydrogen bonding that allows one to
      obtain an analytic expression for the number of bonds per water molecule as a
      function of both its distance to a solute and solute radius. Incorporating that
      approach into the density functional theory, one can examine the solute size
      effects on its hydration over the entire small-to-large lengthscale range at a
      series of different temperatures. Knowing the dependence of the hydration free
      energy on the temperature and solute size, one can also obtain its enthalpic and
      entropic contributions as functions of both temperature and solute size. These
      functions can provide some interesting insight into the temperature dependence of
      the crossover lengthscale of hydrophobic hydration. The model was applied to the
      hydration of spherical particles of various radii in water in the temperature
      range from T = 293.15 K to T = 333.15 K. The model predictions for the
      temperature dependence of the hydration free energy of small hydrophobes are
      consistent with the experimental and simulational data on the hydration of simple
      molecular solutes. Three alternative definitions for the small-to-large crossover
      length-scale of hydrophobic hydration are proposed, and their temperature
      dependence is obtained. Depending on the definition and temperature, the small-to
      large crossover in the hydration mechanism is predicted to occur for hydrophobes
      of radii from one to several nanometers. Independent of its definition, the
      crossover length-scale is predicted to decrease with increasing temperature. 

PMID- 24320294
TI  - Modifying ceria (111) with a TiO2 nanocluster for enhanced reactivity.
AB  - Modification of ceria catalysts is of great interest for oxidation reactions such
      as oxidative dehydrogenation of alcohols. Improving the reactivity of ceria based
      catalysts for these reactions means that they can be run at lower temperatures
      and density functional theory (DFT) simulations of new structures and
      compositions are proving valuable in the development of these catalysts. In this
      paper, we have used DFT+U (DFT corrected for on-site Coulomb interactions) to
      examine the reactivity of a novel modification of ceria, namely, modifying with
      TiO2, using the example of a Ti2O4 species adsorbed on the ceria (111) surface.
      The oxygen vacancy formation energy in the Ti2O4-CeO2 system is significantly
      reduced over the bare ceria surfaces, which together with previous work on ceria
      titania indicates that the presence of the interface favours oxygen vacancy
      formation. The energy gain upon hydrogenation of the catalyst, which is the rate
      determining step in oxidative dehydrogenation, further points to the improved
      oxidation power of this catalyst structure. 

PMID- 24320295
TI  - Determination of the individual atomic site contribution to the electronic
      structure of 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA).
AB  - We have studied the element and orbital-specific electronic structure of thin
      films of 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) using a
      combination of synchrotron radiation-exited resonant x-ray emission spectroscopy,
      x-ray absorption spectroscopy, x-ray photoelectron spectroscopy, as well as
      density functional theory calculations. Resonant and non-resonant x-ray emission
      spectroscopies were used to measure the C and O 2p partial densities of state in
      PTCDA. Furthermore, resonant x-ray emission at the C and O K-edges is shown to be
      able to measure the partial densities of states associated with individual atomic
      sites. The flat molecular orientation of PTCDA on various substrates is explained
      in terms of the carbonyl O atom acting as a hydrogen-bond acceptor leading to
      multiple in-plane intermolecular C=O...H-C hydrogen bonding between carbonyl
      groups and the perylene core of the neighboring PTCDA molecules. We support this
      conclusion by comparison of our calculations to measurements of the electronic
      structure using element-, site-, and orbital-selective C and O K-edge resonant x
      ray emission spectroscopy, and photoemission spectroscopy.

PMID- 24320296
TI  - On the infrared fluorescence of monolayer 13CO:NaCl(100).
AB  - Computations are presented to describe and analyze the high levels of infrared
      laser induced vibrational excitation of a monolayer of absorbed (13)CO on a
      NaCl(100) surface. Extending the vibrational site-to-site surface hopping
      technique of Corcelli and Tully, kinetic Monte Carlo computations are used to
      incorporate single-quantum vibrational pooling and depooling of the (13)CO by
      phonon excitation to allow up to the n = 45 vibrational state under different
      lasing conditions. Previously unpredicted pooling peaks at n > 16 are calculated
      and, under the highest fluence conditions, pooling up to the n = 32 state is
      found in the calculation. These results lead to the prediction of a secondary
      local maximum in the dispersed fluorescence of monolayer CO:NaCl(100) under
      sufficiently high fluence excitation conditions. At times on the order of ms, we
      recover similar behavior for both high and low fluence results. The calculations
      confirm that, for situations where the Debye frequency limited n domain
      restriction approximately holds, the vibrational state population deviates from a
      Boltzmann population linearly in n, a result that we have derived earlier
      theoretically for a domain of n restricted to one-phonon transfers. This
      theoretically understood term, linear in n, dominates the Boltzmann term and is
      responsible for the inversion of the population of vibrational states, Pn. 

PMID- 24320297
TI  - Tuning patterning conditions by co-adsorption of gases: Br2 and H2 on Si(001).
AB  - We have studied the co-adsorption of Br2 and H2 on Si(001), and obtained co
      adsorption energies and the surface phase diagram as a function of the chemical
      potential and pressure of the two gases. To do this, we have used density
      functional theory calculations in combination with ab initio atomistic
      thermodynamics. Over large ranges of bromine and hydrogen chemical potentials,
      the favored configuration is found to be either one with only Br atoms adsorbed
      on the surface, at full coverage, in a (3 * 2) pattern, or a fully H-covered
      surface in a (2 * 1) structure. However, we also find regions of the phase
      diagram where there are configurations with either only Br atoms, or Br and H
      atoms, arranged in a two-atom-wide checkerboard pattern with a (4 * 2) surface
      unit cell. Most interestingly, we find that by co-adsorbing with H2, we bring
      this pattern into a region of the phase diagram corresponding to pressures that
      are significantly higher than those where it is observed with Br2 alone. We also
      find small regions of the phase diagram with several other interesting patterns. 

PMID- 24320298
TI  - Phase behaviors of supramolecular graft copolymers with reversible bonding.
AB  - Phase behaviors of supramolecular graft copolymers with reversible bonding
      interactions were examined by the random-phase approximation and real-space
      implemented self-consistent field theory. The studied supramolecular graft
      copolymers consist of two different types of mutually incompatible yet reactive
      homopolymers, where one homopolymer (backbone) possesses multifunctional groups
      that allow second homopolymers (grafts) to be placed on. The calculations carried
      out show that the bonding strength exerts a pronounced effect on the phase
      behaviors of supramolecular graft copolymers. The length ratio of backbone to
      graft and the positions of functional groups along the backbone are also of
      importance to determine the phase behaviors. Phase diagrams were constructed at
      high bonding strength to illustrate this architectural dependence. It was found
      that the excess unbounded homopolymers swell the phase domains and shift the
      phase boundaries. The results were finally compared with the available
      experimental observations, and a well agreement is shown. The present work could,
      in principle, provide a general understanding of the phase behaviors of
      supramolecular graft copolymers with reversible bonding. 

PMID- 24320299
TI  - Phase behavior of the modified-Yukawa fluid and its sticky limit.
AB  - Simple model systems with short-range attractive potentials have turned out to
      play a crucial role in determining theoretically the phase behavior of proteins
      or colloids. However, as pointed out by D. Gazzillo [J. Chem. Phys. 134, 124504
      (2011)], one of these widely used model potentials, namely, the attractive hard
      core Yukawa potential, shows an unphysical behavior when one approaches its
      sticky limit, since the second virial coefficient is diverging. However, it is
      exactly this second virial coefficient that is typically used to depict the
      experimental phase diagram for a large variety of complex fluids and that, in
      addition, plays an important role in the Noro-Frenkel scaling law [J. Chem. Phys.
      113, 2941 (2000)], which is thus not applicable to the Yukawa fluid. To overcome
      this deficiency of the attractive Yukawa potential, D. Gazzillo has proposed the
      so-called modified hard-core attractive Yukawa fluid, which allows one to
      correctly obtain the second and third virial coefficients of adhesive hard
      spheres starting from a system with an attractive logarithmic Yukawa-like
      interaction. In this work we present liquid-vapor coexistence curves for this
      system and investigate its behavior close to the sticky limit. Results have been
      obtained with the self-consistent Ornstein-Zernike approximation (SCOZA) for
      values of the reduced inverse screening length parameter up to 18. The accuracy
      of SCOZA has been assessed by comparison with Monte Carlo simulations. 

PMID- 24320300
TI  - Micellar interactions in water-AOT based droplet microemulsions containing
      hydrophilic and amphiphilic polymers.
AB  - We investigate the influence of addition of hydrophilic and amphiphilic polymer
      on percolation behavior and micellar interactions in AOT-based water-in-oil
      droplet microemulsions. We focus on two series of samples having constant molar
      water to surfactant ratio W = 20 and constant droplet volume fraction Phi = 30%,
      respectively. From dielectric spectroscopy experiments, we extract the bending
      rigidity of the surfactant shell by percolation temperature measurements.
      Depending on droplet size, we find stabilization and destabilization of the
      surfactant shell upon addition of hydrophilic poly(ethylene glycol) (PEG) (Mn =
      3100 g mol(-1)) and amphiphilic poly(styrene)-b-poly(ethylene glycol) copolymer
      with comparable length of the hydrophilic block. Complementary small angle X-ray
      scattering experiments corroborate the finding of stabilization for smaller
      droplets and destabilization of larger droplets. Subsequent analysis of
      dielectric spectra enables us to extract detailed information about micellar
      interactions and clustering by evaluating the dielectric high frequency shell
      relaxation. We interpret the observed results as a possible modification of the
      inter-droplet charge transfer efficiency by addition of PEG polymer, while the
      amphiphilic polymer shows a comparable, but dampened effect. 

PMID- 24320301
TI  - Chain conformations of ring polymers under theta conditions studied by Monte
      Carlo simulation.
AB  - We studied equilibrium conformations of trivial-, 31-knot, and 51-knot ring
      polymers with finite chain length at their theta-conditions using a Monte Carlo
      simulation. The polymer chains treated in this study were composed of beads and
      bonds on a face-centered-cubic lattice respecting the excluded volume. The
      Flory's critical exponent nu in Rg ~ N(nu) relationship was obtained from the
      dependence of the radius of gyration, Rg, on the segment number of polymers, N.
      In this study, the temperatures at which nu equal 1/2 are defined as theta
      temperatures of several ring molecules. The theta-temperatures for trivial-, 31
      knot, and 51-knot ring polymers are lower than that for a linear polymer in N <=
      4096, where their topologies are fixed by their excluded volumes. The radial
      distribution functions of the segments in each molecule are obtained at their
      theta-temperatures. The functions of linear- and trivial-ring polymers have been
      found to be expressed by those of Gaussian and closed-Gaussian chains,
      respectively. At the theta-conditions, the excluded volumes of chains and the
      topological-constraints of trivial-ring polymers can be apparently screened by
      the attractive force between segments, and the <Rg(2)> values for trivial ring
      polymers are larger than the half of those for linear polymers. In the finite N
      region the topological-constraints of 31- and 51-knot rings are stronger than
      that of trivial-ring, and trajectories of the knotted ring polymers cannot be
      described as a closed Gaussian even though they are under theta-conditions.

PMID- 24320302
TI  - Density functional theory study of neutral and oxidized thiophene oligomers.
AB  - The effect of oxidation on the energetics and structure of thiophene (Th)
      oligomers is studied with density functional theory at the B3PW91/6-311++G(d,p)
      level. Neutral n-Th oligomers (2 < n < 13) are gently curved planar chains.
      Ionization potential and electron affinity results show that n-Th oligomers are
      easier to be oxidized as their chain length increases. Oxidation states +2, +4,
      +6, and +8 are energetically stable in 12-Th. Upon oxidation the conjugated
      backbone of 12-Th switches from extended benzenoid phase to quinoid phase
      localized on groups of monomers regularly spaced along the chain. Oxidized states
      +2, +4, +6, and +8 of 12-Th display two +1e localized at the ends of their chains
      only because of the finite size of the chains. In 12-Th this end-effect extends
      over the two terminal monomers forming a positive-negative charge duet. This
      peculiar charge localization makes n-Th oligomers different from other conducting
      polymers with similar structure, such as polypyrrole. The spectrum of single
      electron molecular states of oxidized 12-Th displays two localized single
      electron states in the HOMO-LUMO energy gap per +2 oxidation state.
      Oligothiophene 12-Th doped with F atoms at 1:2 concentration presents a charge
      transfer of 3.4 e from oligomer to dopants that increases to 4.8 e in the
      presence of solvent. The charge distribution in these F-doped oligomers is
      similar to the +4 oxidation state of 12-Th. It is predicted that dopants produce
      an enhanced charge transfer localized in the proximity of their locations
      enhancing the formation of bipolarons in the central part of the oligomer chain. 

PMID- 24320303
TI  - Graph representation of protein free energy landscape.
AB  - The thermodynamics and kinetics of protein folding and protein conformational
      changes are governed by the underlying free energy landscape. However, the
      multidimensional nature of the free energy landscape makes it difficult to
      describe. We propose to use a weighted-graph approach to depict the free energy
      landscape with the nodes on the graph representing the conformational states and
      the edge weights reflecting the free energy barriers between the states. Our
      graph is constructed from a molecular dynamics trajectory and does not involve
      projecting the multi-dimensional free energy landscape onto a low-dimensional
      space defined by a few order parameters. The calculation of free energy barriers
      was based on transition-path theory using the MSMBuilder2 package. We compare our
      graph with the widely used transition disconnectivity graph (TRDG) which is
      constructed from the same trajectory and show that our approach gives more
      accurate description of the free energy landscape than the TRDG approach even
      though the latter can be organized into a simple tree representation. The
      weighted-graph is a general approach and can be used on any complex system. 

PMID- 24320304
TI  - Note: transient negative ions as initiators of oxygen fixation in <20 eV electron
      irradiated DNA.

PMID- 24320307
TI  - Communication: reduced density matrices in molecular systems: grand-canonical
      electron states.
AB  - Grand-canonical like descriptions of many electron atomic and molecular open
      systems which are characterized by a non-integer number of electrons are
      presented. Their associated reduced density matrices (RDMs) are obtained by
      introducing the contracting mapping for this type of distributions. It is shown
      that there is loss of information when connecting RDMs of different order by
      partial contractions. The energy convexity property of these systems simplifies
      the description. Consequently, this formulation opens the possibility to a new
      look for chemical descriptors such as chemical potential and reactivity among
      others. Examples are presented to discuss the theoretical aspects of this work. 

PMID- 24320308
TI  - Communication: two-component ring-coupled-cluster computation of the correlation
      energy in the random-phase approximation.
AB  - Within the framework of density-functional theory, the correlation energy is
      computed in the random-phase approximation (RPA) using spinors obtained from a
      two-component relativistic Kohn-Sham calculation accounting for spin-orbit
      interactions. Ring-coupled-cluster equations are solved to obtain the two
      component RPA correlation energy. Results are presented for the hydrides of the
      halogens Br, I, and At as well as of the coinage metals Cu, Ag, and Au, based on
      two-component relativistic exact-decoupling Kohn-Sham calculations. 

PMID- 24320309
TI  - Communication: electronic and transport properties of molecular junctions under a
      finite bias: a dual mean field approach.
AB  - We show that when a molecular junction is under an external bias, its properties
      cannot be uniquely determined by the total electron density in the same manner as
      the density functional theory for ground state properties. In order to correctly
      incorporate bias-induced nonequilibrium effects, we present a dual mean field
      (DMF) approach. The key idea is that the total electron density together with the
      density of current-carrying electrons are sufficient to determine the properties
      of the system. Two mean fields, one for current-carrying electrons and the other
      one for equilibrium electrons can then be derived. Calculations for a graphene
      nanoribbon junction show that compared with the commonly used ab initio transport
      theory, the DMF approach could significantly reduce the electric current at low
      biases due to the non-equilibrium corrections to the mean field potential in the
      scattering region. 

PMID- 24320310
TI  - Linear-scaling explicitly correlated treatment of solids: periodic local MP2-F12
      method.
AB  - Theory and implementation of the periodic local MP2-F12 method in the 3*A fixed
      amplitude ansatz is presented. The method is formulated in the direct space,
      employing local representation for the occupied, virtual, and auxiliary orbitals
      in the form of Wannier functions (WFs), projected atomic orbitals (PAOs), and
      atom-centered Gaussian-type orbitals, respectively. Local approximations are
      introduced, restricting the list of the explicitly correlated pairs, as well as
      occupied, virtual, and auxiliary spaces in the strong orthogonality projector to
      the pair-specific domains on the basis of spatial proximity of respective
      orbitals. The 4-index two-electron integrals appearing in the formalism are
      approximated via the direct-space density fitting technique. In this procedure,
      the fitting orbital spaces are also restricted to local fit-domains surrounding
      the fitted densities. The formulation of the method and its implementation
      exploits the translational symmetry and the site-group symmetries of the WFs.
      Test calculations are performed on LiH crystal. The results show that the
      periodic LMP2-F12 method substantially accelerates basis set convergence of the
      total correlation energy, and even more so the correlation energy differences.
      The resulting energies are quite insensitive to the resolution-of-the-identity
      domain sizes and the quality of the auxiliary basis sets. The convergence with
      the orbital domain size is somewhat slower, but still acceptable. Moreover,
      inclusion of slightly more diffuse functions, than those usually used in the
      periodic calculations, improves the convergence of the LMP2-F12 correlation
      energy with respect to both the size of the PAO-domains and the quality of the
      orbital basis set. At the same time, the essentially diffuse atomic orbitals from
      standard molecular basis sets, commonly utilized in molecular MP2-F12
      calculations, but problematic in the periodic context, are not necessary for LMP2
      F12 treatment of crystals. 

PMID- 24320311
TI  - Self-interaction corrected density functional calculations of molecular Rydberg
      states.
AB  - A method is presented for calculating the wave function and energy of Rydberg
      excited states of molecules. A good estimate of the Rydberg state orbital is
      obtained using ground state density functional theory including Perdew-Zunger
      self-interaction correction and an optimized effective potential. The total
      energy of the excited molecule is obtained using the Delta Self-Consistent Field
      method where an electron is removed from the highest occupied orbital and placed
      in the Rydberg orbital. Results are presented for the first few Rydberg states of
      NH3, H2O, H2CO, C2H4, and N(CH3)3. The mean absolute error in the energy of the
      33 molecular Rydberg states presented here is 0.18 eV. The orbitals are
      represented on a real space grid, avoiding the dependence on diffuse atomic basis
      sets. As in standard density functional theory calculations, the computational
      effort scales as NM(2) where N is the number of orbitals and M is the number of
      grid points included in the calculation. Due to the slow scaling of the
      computational effort with system size and the high level of parallelism in the
      real space grid approach, the method presented here makes it possible to estimate
      Rydberg electron binding energy in large molecules. 

PMID- 24320312
TI  - Reversible diffusion-influenced reactions of an isolated pair on some two
      dimensional surfaces.
AB  - We investigate reversible diffusion-influenced reactions of an isolated pair in
      two dimensions. To this end, we employ convolution relations that permit deriving
      the survival probability of the reversible reaction directly in terms of the
      survival probability of the irreversible reaction. Furthermore, we make use of
      the mean reaction time approximation to write the irreversible survival
      probability in restricted spaces as a single exponential. In this way, we obtain
      exact and approximative expressions in the time domain for the reversible
      survival probability for three different two dimensional spatial domains: The
      infinite plane, the annular domain, and the surface of a sphere. Our obtained
      results should prove useful in the context of membrane-bound reversible diffusion
      influenced reactions in cell biology. 

PMID- 24320313
TI  - Charge transfer interaction using quasiatomic minimal-basis orbitals in the
      effective fragment potential method.
AB  - The charge transfer (CT) interaction, the most time-consuming term in the general
      effective fragment potential method, is made much more computationally efficient.
      This is accomplished by the projection of the quasiatomic minimal-basis-set
      orbitals (QUAMBOs) as the atomic basis onto the self-consistent field virtual
      molecular orbital (MO) space to select a subspace of the full virtual space
      called the valence virtual space. The diagonalization of the Fock matrix in terms
      of QUAMBOs recovers the canonical occupied orbitals and, more importantly, gives
      rise to the valence virtual orbitals (VVOs). The CT energies obtained using VVOs
      are generally as accurate as those obtained with the full virtual space canonical
      MOs because the QUAMBOs span the valence part of the virtual space, which can
      generally be regarded as "chemically important." The number of QUAMBOs is the
      same as the number of minimal-basis MOs of a molecule. Therefore, the number of
      VVOs is significantly smaller than the number of canonical virtual MOs,
      especially for large atomic basis sets. This leads to a dramatic decrease in the
      computational cost. 

PMID- 24320314
TI  - The Jastrow antisymmetric geminal power in Hilbert space: theory, benchmarking,
      and application to a novel transition state.
AB  - The Jastrow-modified antisymmetric geminal power (JAGP) ansatz in Hilbert space
      successfully overcomes two key failings of other pairing theories, namely, a lack
      of inter-pair correlations and a lack of multiple resonance structures, while
      maintaining a polynomially scaling cost, variational energies, and size
      consistency. Here, we present efficient quantum Monte Carlo algorithms that
      evaluate and optimize the JAGP energy for a cost that scales as the fifth power
      of the system size. We demonstrate the JAGP's ability to describe both static and
      dynamic correlation by applying it to bond stretching in H2O, C2, and N2 as well
      as to a novel, multi-reference transition state of ethene. JAGP's accuracy in
      these systems outperforms even the most sophisticated single-reference methods
      and approaches that of exponentially scaling active space methods. 

PMID- 24320315
TI  - General active space commutator-based coupled cluster theory of general
      excitation rank for electronically excited states: implementation and application
      to ScH.
AB  - We present a new implementation of general excitation rank coupled cluster theory
      for electronically excited states based on the single-reference multi-reference
      formalism. The method may include active-space selected and/or general higher
      excitations by means of the general active space concept. It may employ molecular
      integrals over the four-component Levy-Leblond Hamiltonian or the relativistic
      spin-orbit-free four-component Hamiltonian of Dyall. In an initial application to
      ground- and excited states of the scandium monohydride molecule we report
      spectroscopic constants using basis sets of up to quadruple-zeta quality and up
      to full iterative triple excitations in the cluster operators. Effects due to
      spin-orbit interaction are evaluated using two-component multi-reference
      configuration interaction for assessing the accuracy of the coupled cluster
      results. 

PMID- 24320316
TI  - Effect of an external electric field on the diffusion-influenced geminate
      reversible reaction of a neutral particle and a charged particle in three
      dimensions. III. Ground-state ABCD reaction.
AB  - In the presence of an external electric field, the ground-state A+B(q)<->C(q)+D
      diffusion-influenced reversible reaction for a geminate pair, a neutral and a
      charged particle, is investigated in three dimensions. The probability density
      functions, the rates of reactions, and the survival probabilities of individual
      particles are analytically derived in the Laplace domain in terms of series
      solutions. The long-time kinetics of probability density functions and rates of
      reactions in rescaled forms shows a kinetic transition behavior from a t(-3/2)
      power law to a t(-3/2)e(t) increase when the condition D1F1 (2)<=D2F2 (2), which
      depends on the diffusivities of particles and the external electric fields,
      changes to D1F1 (2)>D2F2 (2). In the transition region D1F1 (2)=D2F2 (2), the
      long-time behavior also shows a t(-3/2) power law decay but with a different
      value of the prefactor. The rescaled survival probabilities only exhibit an
      exponentially increasing behavior at long times with no dependence on the various
      values of parameters.

PMID- 24320317
TI  - A second-order multi-reference perturbation method for molecular vibrations.
AB  - We present a general multi-reference framework for treating strong correlation in
      vibrational structure theory, which we denote the vibrational active space self
      consistent field (VASSCF) approach. Active configurations can be selected
      according to excitation level or the degrees of freedom involved, or both. We
      introduce a novel state-specific second-order multi-configurational perturbation
      correction that accounts for the remaining weak correlation between the
      vibrational modes. The resulting VASPT2 method is capable of accurately and
      efficiently treating strong correlation in the form of large anharmonic
      couplings, at the same time as correctly resolving resonances between states.
      These methods have been implemented in our new dynamics package DYNAMOL, which
      can currently treat up to four-body Hamiltonian coupling terms. We present a
      pilot application of the VASPT2 method to the trans isomer of formic acid. We
      have constructed a new analytic potential that reproduces frozen core
      CCSD(T)(F12*)/cc-pVDZ-F12 energies to within 0.25% RMSD over the energy range 0
      15 000 cm(-1). The computed VASPT2 fundamental transition energies are accurate
      to within 9 cm(-1) RMSD from experimental values, which is close to the accuracy
      one can expect from a CCSD(T) potential energy surface.

PMID- 24320319
TI  - Adaptive spectral clustering with application to tripeptide conformation
      analysis.
AB  - A decomposition of a molecular conformational space into sets or functions
      (states) allows for a reduced description of the dynamical behavior in terms of
      transition probabilities between these states. Spectral clustering of the
      corresponding transition probability matrix can then reveal metastabilities. The
      more states are used for the decomposition, the smaller the risk to cover
      multiple conformations with one state, which would make these conformations
      indistinguishable. However, since the computational complexity of the clustering
      algorithm increases quadratically with the number of states, it is desirable to
      have as few states as possible. To balance these two contradictory goals, we
      present an algorithm for an adaptive decomposition of the position space starting
      from a very coarse decomposition. The algorithm is applied to small data
      classification problems where it was shown to be superior to commonly used
      algorithms, e.g., k-means. We also applied this algorithm to the conformation
      analysis of a tripeptide molecule where six-dimensional time series are
      successfully analyzed. 

PMID- 24320318
TI  - Multiscale multiphysics and multidomain models--flexibility and rigidity.
AB  - The emerging complexity of large macromolecules has led to challenges in their
      full scale theoretical description and computer simulation. Multiscale
      multiphysics and multidomain models have been introduced to reduce the number of
      degrees of freedom while maintaining modeling accuracy and achieving
      computational efficiency. A total energy functional is constructed to put
      energies for polar and nonpolar solvation, chemical potential, fluid flow,
      molecular mechanics, and elastic dynamics on an equal footing. The variational
      principle is utilized to derive coupled governing equations for the above
      mentioned multiphysical descriptions. Among these governing equations is the
      Poisson-Boltzmann equation which describes continuum electrostatics with atomic
      charges. The present work introduces the theory of continuum elasticity with
      atomic rigidity (CEWAR). The essence of CEWAR is to formulate the shear modulus
      as a continuous function of atomic rigidity. As a result, the dynamics complexity
      of a macromolecular system is separated from its static complexity so that the
      more time-consuming dynamics is handled with continuum elasticity theory, while
      the less time-consuming static analysis is pursued with atomic approaches. We
      propose a simple method, flexibility-rigidity index (FRI), to analyze
      macromolecular flexibility and rigidity in atomic detail. The construction of FRI
      relies on the fundamental assumption that protein functions, such as flexibility,
      rigidity, and energy, are entirely determined by the structure of the protein and
      its environment, although the structure is in turn determined by all the
      interactions. As such, the FRI measures the topological connectivity of protein
      atoms or residues and characterizes the geometric compactness of the protein
      structure. As a consequence, the FRI does not resort to the interaction
      Hamiltonian and bypasses matrix diagonalization, which underpins most other
      flexibility analysis methods. FRI's computational complexity is of O(N(2)) at
      most, where N is the number of atoms or residues, in contrast to O(N(3)) for
      Hamiltonian based methods. We demonstrate that the proposed FRI gives rise to
      accurate prediction of protein B-Factor for a set of 263 proteins. We show that a
      parameter free FRI is able to achieve about 95% accuracy of the parameter
      optimized FRI. An interpolation algorithm is developed to construct continuous
      atomic flexibility functions for visualization and use with CEWAR. 

PMID- 24320320
TI  - Dehydrogenation of N2HX (X=2-4) by nitrogen atoms: thermochemical and kinetics.
AB  - Thermochemical and kinetics of sequential hydrogen abstraction reactions from
      hydrazine by nitrogen atoms were studied. The dehydrogenation was divided in
      three steps, N2H4 + N, N2H3 + N, and N2H2 + N. The thermal rate constants were
      calculated within the framework of canonical variational theory, with zero and
      small curvature multidimensional tunnelling corrections. The reaction paths were
      computed with the BB1K/aug-cc-pVTZ method and the thermochemical properties were
      improved with the CCSD(T)/CBS//BB1K/aug-cc-pVTZ approach. The first
      dehydrogenation step presents the lowest rate constants, equal to 1.22 * 10(-20)
      cm(3) molecule(-1) s(-1) at 298 K. 

PMID- 24320321
TI  - A search for the sulphur hexafluoride cation with intense, few cycle laser
      pulses.
AB  - It is well established that upon ionization of sulphur hexafluoride, the SF6(+)
      ion is never observed in mass spectra. Recent work with ultrashort intense laser
      pulses has offered indications that when strong optical field are used, the
      resulting "bond hardening" can induce changes in the potential energy surfaces of
      molecular cations such that molecular ions that are normally unstable may,
      indeed, become metastable enough to enable their detection by mass spectrometry.
      Do intense, ultrashort laser pulses permit formation of SF6(+)? We have utilized
      intense pulses of 5 fs, 11 fs, and 22 fs to explore this possibility. Our results
      are negative: no evidence is discovered for SF6(+). However, multiply charged
      sulphur and fluorine ions from highly charged SF6(q+) ions are observed that
      enable us to resolve the controversy regarding the kinetic energy release
      accompanying formation of F(+) fragment ions. Quantum chemical computations of
      field-distorted potential energy curves of SF6 and its molecular ion enable us to
      rationalize our non-observation of SF6(+). Our findings have implications for
      high harmonic generation from SF6 in the few-cycle regime.

PMID- 24320322
TI  - Electronic transitions of palladium dimer.
AB  - The laser induced fluorescence spectrum of palladium dimer (Pd2) in the visible
      region between 480 and 700 nm has been observed and analyzed. The gas-phase Pd2
      molecule was produced by laser ablation of palladium metal rod. Eleven
      vibrational bands were observed and assigned to the [17.1](3)Pig-X(3)Sigmau(+)
      transition system. The bond length (ro) and vibrational frequency (DeltaG1/2) of
      the ground X(3)Sigmau(+) state were determined to be 2.47(4) A and 211.4(5) cm(
      1), respectively. A molecular orbital energy level diagram was used to understand
      the observed ground and excited electronic states. This is the first gas-phase
      experimental investigation of the electronic transitions of Pd2.

PMID- 24320323
TI  - Ab initio potential energy surface for the highly nonlinear dynamics of the KCN
      molecule.
AB  - An accurate ab initio quantum chemistry study at level of quadratic configuration
      interaction method of the electronic ground state of the KCN molecule is
      presented. A fitting of the results to an analytical series expansion was
      performed to obtain a global potential energy surface suitable for the study of
      the associated vibrational dynamics. Additionally, classical Poincare surfaces of
      section for different energies and quantum eigenstates were calculated, showing
      the highly nonlinear behavior of this system. 

PMID- 24320324
TI  - Chemical reaction versus vibrational quenching in low energy collisions of
      vibrationally excited OH with O.
AB  - Quantum scattering calculations are reported for state-to-state vibrational
      relaxation and reactive scattering in O + OH(v = 2 - 3, j = 0) collisions on the
      electronically adiabatic ground state (2)A'' potential energy surface of the HO2
      molecule. The time-independent Schrodinger equation in hyperspherical coordinates
      is solved to determine energy dependent probabilities and cross sections over
      collision energies ranging from ultracold to 0.35 eV and for total angular
      momentum quantum number J = 0. A J-shifting approximation is then used to compute
      initial state selected reactive rate coefficients in the temperature range T = 1 
      400 K. Results are found to be in reasonable agreement with available
      quasiclassical trajectory calculations. Results indicate that rate coefficients
      for O2 formation increase with increasing the OH vibrational level except at low
      and ultralow temperatures where OH(v = 0) exhibits a slightly different trend. It
      is found that vibrational relaxation of OH in v = 2 and v = 3 vibrational levels
      is dominated by a multi-quantum process. 

PMID- 24320325
TI  - Resonant photoelectron spectroscopy of Au2(-) via a Feshbach state using high
      resolution photoelectron imaging.
AB  - Photodetachment cross sections are measured across the detachment threshold of
      Au2(-) between 1.90 and 2.02 eV using a tunable laser. In addition to obtaining a
      more accurate electron affinity for Au2 (1.9393 +/- 0.0003 eV), we observe eight
      resonances above the detachment threshold, corresponding to excitations from the
      vibrational levels of the Au2(-) ground state (X(2)Sigmau(+)) to those of a
      metastable excited state of Au2(-) (or Feshbach resonances) at an excitation
      energy of 1.9717 +/- 0.0003 eV and a vibrational frequency of 129.1 +/- 1.5 cm(
      1). High-resolution photoelectron spectra of Au2(-) are obtained using
      photoelectron imaging to follow the autodetachment processes by tuning the
      detachment laser to all the eight Feshbach resonances. We observe significant non
      Franck-Condon behaviors in the resonant photoelectron spectra due to
      autodetachment from a given vibrational level of the Feshbach state to selective
      vibrational levels of the neutral final state. Using the spectroscopic data for
      the ground states of Au2(-) (X(2)Sigmau(+)) and Au2(X(1)Sigmag(+)), we estimate
      an equilibrium bond distance of 2.53 +/- 0.02 A for the Feshbach state of Au2(-)
      by simulating the Franck-Condon factors for the resonant excitation and
      autodetachment processes.

PMID- 24320326
TI  - Solvent dependent branching between C-I and C-Br bond cleavage following 266 nm
      excitation of CH2BrI.
AB  - It is well known that ultraviolet photoexcitation of halomethanes results in
      halogen-carbon bond cleavage. Each halogen-carbon bond has a dominant ultraviolet
      (UV) absorption that promotes an electron from a nonbonding halogen orbital (nX)
      to a carbon-halogen antibonding orbital (sigma*C-X). UV absorption into specific
      transitions in the gas phase results primarily in selective cleavage of the
      corresponding carbon-halogen bond. In the present work, broadband ultrafast UV
      visible transient absorption studies of CH2BrI reveal a more complex
      photochemistry in solution. Transient absorption spectra are reported spanning
      the range from 275 nm to 750 nm and 300 fs to 3 ns following excitation of CH2BrI
      at 266 nm in acetonitrile, 2-butanol, and cyclohexane. Channels involving
      formation of CH2Br + I radical pairs, iso-CH2Br-I, and iso-CH2I-Br are
      identified. The solvent environment has a significant influence on the branching
      ratios, and on the formation and stability of iso-CH2Br-I. Both iso-CH2Br-I and
      iso-CH2I-Br are observed in cyclohexane with a ratio of ~2.8:1. In acetonitrile
      this ratio is 7:1 or larger. The observation of formation of iso-CH2I-Br
      photoproduct as well as iso-CH2Br-I following 266 nm excitation is a novel result
      that suggests complexity in the dissociation mechanism. We also report a solvent
      and concentration dependent lifetime of iso-CH2Br-I. At low concentrations the
      lifetime is >4 ns in acetonitrile, 1.9 ns in 2-butanol and ~1.4 ns in
      cyclohexane. These lifetimes decrease with higher initial concentrations of
      CH2BrI. The concentration dependence highlights the role that intermolecular
      interactions can play in the quenching of unstable isomers of dihalomethanes.

PMID- 24320327
TI  - Many-body Green's function GW and Bethe-Salpeter study of the optical excitations
      in a paradigmatic model dipeptide.
AB  - We study within the many-body Green's function GW and Bethe-Salpeter formalisms
      the excitation energies of a paradigmatic model dipeptide, focusing on the four
      lowest-lying local and charge-transfer excitations. Our GW calculations are
      performed at the self-consistent level, updating first the quasiparticle
      energies, and further the single-particle wavefunctions within the static Coulomb
      hole plus screened-exchange approximation to the GW self-energy operator.
      Important level crossings, as compared to the starting Kohn-Sham LDA spectrum,
      are identified. Our final Bethe-Salpeter singlet excitation energies are found to
      agree, within 0.07 eV, with CASPT2 reference data, except for one charge-transfer
      state where the discrepancy can be as large as 0.5 eV. Our results agree best
      with LC-BLYP and CAM-B3LYP calculations with enhanced long-range exchange, with a
      0.1 eV mean absolute error. This has been achieved employing a parameter-free
      formalism applicable to metallic or insulating extended or finite systems. 

PMID- 24320328
TI  - Exact quantum scattering calculations of transport properties for the H2O-H
      system.
AB  - Transport properties for collisions of water with hydrogen atoms are computed by
      means of exact quantum scattering calculations. For this purpose, a potential
      energy surface (PES) was computed for the interaction of rigid H2O, frozen at its
      equilibrium geometry, with a hydrogen atom, using a coupled-cluster method that
      includes all singles and doubles excitations, as well as perturbative
      contributions of connected triple excitations. To investigate the importance of
      the anisotropy of the PES on transport properties, calculations were performed
      with the full potential and with the spherical average of the PES. We also
      explored the determination of the spherical average of the PES from radial cuts
      in six directions parallel and perpendicular to the C2 axis of the molecule.
      Finally, the computed transport properties were compared with those computed with
      a Lennard-Jones 12-6 potential. 

PMID- 24320329
TI  - Electronic structure and UV spectrum of hexachloroplatinate dianions in vacuo.
AB  - We present a joint experimental and theoretical study of the electronic spectrum
      of hexachloroplatinate dianion. We have measured electronic photodissociation and
      photodetachment spectra of mass-selected PtCl6(2-) ions in vacuo and compare
      these with calculated band positions from time-dependent density functional
      theory and from relativistic calculations. Excitation of an electronic transition
      of the dianion leads to resonant enhancement of the photodetachment cross section
      superimposed on direct detachment. Photoexcitation results in loss of Cl(-) and
      Cl(0), depending on photon energy. The photofragmentation spectrum for formation
      of the PtCl4(-) fragment ion mirrors the UV/vis absorption spectrum of PtCl6(2-)
      in solution with a small solvatochromic shift.

PMID- 24320330
TI  - A density functional theory study of magneto-electric Jones birefringence of
      noble gases, furan homologues, and mono-substituted benzenes.
AB  - We report on the results of a systematic ab initio study of the Jones
      birefringence of noble gases, of furan homologues, and of monosubstituted
      benzenes, in the gas phase, with the aim of analyzing the behavior and the trends
      within a list of systems of varying size and complexity, and of identifying
      candidates for a combined experimental/theoretical study of the effect. We resort
      here to analytic linear and nonlinear response functions in the framework of time
      dependent density functional theory. A correlation is made between the observable
      (the Jones constant) and the atomic radius for noble gases, or the permanent
      electric dipole and a structure/chemical reactivity descriptor as the para
      Hammett constant for substituted benzenes. 

PMID- 24320331
TI  - Low-pressure line-shape study in molecular oxygen with absolute frequency
      reference.
AB  - We present a line-shape analysis of the rovibronic R1 Q2 transition of the oxygen
      B band resolved by the Pound-Drever-Hall-locked frequency-stabilized cavity ring
      down spectroscopy technique in the low pressure range. The frequency axis of the
      spectra is linked by the ultra-narrow diode laser to the optical frequency comb
      in order to measure the absolute frequency at each point of the recorded spectra.
      Experimental spectra are fitted with various line-shape models: the Voigt
      profile, the Galatry profile, the Nelkin-Ghatak profile, the speed-dependent
      Voigt profile, and the speed-dependent Nelkin-Ghatak profile with quadratic and
      hypergeometric approximations for the speed dependence of collisional broadening
      and shifting. The influences of Dicke narrowing, speed-dependent effects, and
      correlation between phase- and velocity-changing collisions on the line shape are
      investigated. Values of line-shape parameters, including the absolute frequency
      of the transition 435685.24828(46) GHz, are reported. 

PMID- 24320332
TI  - Generation and reactivity of putative support systems, Ce-Al neutral binary oxide
      nanoclusters: CO oxidation and C-H bond activation.
AB  - Both ceria (CeO2) and alumina (Al2O3) are very important catalyst support
      materials. Neutral binary oxide nanoclusters (NBONCs), CexAlyOz, are generated
      and detected in the gas phase and their reactivity with carbon monoxide (CO) and
      butane (C4H10) is studied. The very active species CeAlO4 (?) can react with CO
      and butane via O atom transfer (OAT) and H atom transfer (HAT), respectively.
      Other CexAlyOz NBONCs do not show reactivities toward CO and C4H10. The
      structures, as well as the reactivities, of CexAlyOz NBONCs are studied
      theoretically employing density functional theory (DFT) calculations. The ground
      state CeAlO4 (?) NBONC possesses a kite-shaped structure with an OtCeObObAlOt
      configuration (Ot, terminal oxygen; Ob, bridging oxygen). An unpaired electron is
      localized on the Ot atom of the AlOt moiety rather than the CeOt moiety: this Ot
      centered radical moiety plays a very important role for the reactivity of the
      CeAlO4 (?) NBONC. The reactivities of Ce2O4, CeAlO4 (?), and Al2O4 toward CO are
      compared, emphasizing the importance of a spin-localized terminal oxygen for
      these reactions. Intramolecular charge distributions do not appear to play a role
      in the reactivities of these neutral clusters, but could be important for charged
      isoelectronic BONCs. DFT studies show that the reaction of CeAlO4 (?) with C4H10
      to form the CeAlO4H?C4H9 (?) encounter complex is barrierless. While HAT
      processes have been previously characterized for cationic and anionic oxide
      clusters, the reported study is the first observation of a HAT process supported
      by a ground state neutral oxide cluster. Mechanisms for catalytic oxidation of CO
      over surfaces of AlxOy/MmOn or MmOn/AlxOy materials are proposed consistent with
      the presented experimental and theoretical results. 

PMID- 24320333
TI  - Liquid chloroform structure from computer simulation with a full ab initio
      intermolecular interaction potential.
AB  - We have calculated the intermolecular interaction energies of the chloroform
      dimer in 12 orientations using the second-order Moller-Plesset perturbation
      theory. Single point energies of important geometries were calibrated by the
      coupled cluster with single and double and perturbative triple excitation method.
      Dunning's correlation consistent basis sets up to aug-cc-pVQZ have been employed
      in extrapolating the interaction energies to the complete basis set limit values.
      With the ab initio potential data we constructed a 5-site force field model for
      molecular dynamics simulations. We compared the simulation results with recent
      experiments and obtained quantitative agreements for the detailed atomwise radial
      distribution functions. Our results were also consistent with previous results
      using empirical force fields with polarization effects. Moreover, the calculated
      diffusion coefficients reproduced the experimental data over a wide range of
      thermodynamic conditions. To the best of our knowledge, this is the first ab
      initio force field which is capable of competing with existing empirical force
      fields for liquid chloroform.

PMID- 24320334
TI  - Room temperature compressibility and diffusivity of liquid water from first
      principles.
AB  - The isothermal compressibility of water is essential to understand its anomalous
      properties. We compute it by ab initio molecular dynamics simulations of 200
      molecules at five densities, using two different van der Waals density
      functionals. While both functionals predict compressibilities within ~30% of
      experiment, only one of them accurately reproduces, within the uncertainty of the
      simulation, the density dependence of the self-diffusion coefficient in the
      anomalous region. The discrepancies between the two functionals are explained in
      terms of the low- and high-density structures of the liquid.

PMID- 24320335
TI  - Potential energy landscapes for the 2D XY model: minima, transition states, and
      pathways.
AB  - We describe a numerical study of the potential energy landscape for the two
      dimensional XY model (with no disorder), considering up to 100 spins and central
      processing unit and graphics processing unit implementations of local
      optimization, focusing on minima and saddles of index one (transition states). We
      examine both periodic and anti-periodic boundary conditions, and show that the
      number of stationary points located increases exponentially with increasing
      lattice size. The corresponding disconnectivity graphs exhibit funneled
      landscapes; the global minima are readily located because they exhibit relatively
      large basins of attraction compared to the higher energy minima as the lattice
      size increases. 

PMID- 24320336
TI  - Effects of dilute aqueous NaCl solution on caffeine aggregation.
AB  - The effect of salt concentration on association properties of caffeine molecule
      was investigated by employing molecular dynamics simulations in isothermal
      isobaric ensemble of eight caffeine molecules in pure water and three different
      salt (NaCl) concentrations, at 300 K temperature and 1 atm pressure. The
      concentration of caffeine was taken almost at the solubility limit. With
      increasing salt concentration, we observe enhancement of first peak height and
      appearance of a second peak in the caffeine-caffeine distribution function.
      Furthermore, our calculated solvent accessible area values and cluster structure
      analyses suggest formation of higher order caffeine cluster on addition of salt.
      The calculated hydrogen bond properties reveal that there is a modest decrease in
      the average number of water-caffeine hydrogen bonds on addition of NaCl salt.
      Also observed are: (i) decrease in probability of salt contact ion pair as well
      as decrease in the solvent separated ion pair formation with increasing salt
      concentration, (ii) a modest second shell collapse in the water structure, and
      (iii) dehydration of hydrophobic atomic sites of caffeine on addition of NaCl. 

PMID- 24320337
TI  - Intermolecular potentials and the accurate prediction of the thermodynamic
      properties of water.
AB  - The ability of intermolecular potentials to correctly predict the thermodynamic
      properties of liquid water at a density of 0.998 g/cm(3) for a wide range of
      temperatures (298-650 K) and pressures (0.1-700 MPa) is investigated. Molecular
      dynamics simulations are reported for the pressure, thermal pressure coefficient,
      thermal expansion coefficient, isothermal and adiabatic compressibilities,
      isobaric and isochoric heat capacities, and Joule-Thomson coefficient of liquid
      water using the non-polarizable SPC/E and TIP4P/2005 potentials. The results are
      compared with both experiment data and results obtained from the ab initio-based
      Matsuoka-Clementi-Yoshimine non-additive (MCYna) [J. Li, Z. Zhou, and R. J.
      Sadus, J. Chem. Phys. 127, 154509 (2007)] potential, which includes polarization
      contributions. The data clearly indicate that both the SPC/E and TIP4P/2005
      potentials are only in qualitative agreement with experiment, whereas the
      polarizable MCYna potential predicts some properties within experimental
      uncertainty. This highlights the importance of polarizability for the accurate
      prediction of the thermodynamic properties of water, particularly at temperatures
      beyond 298 K. 

PMID- 24320338
TI  - The dissociative chemisorption of methane on Ni(100) and Ni(111): classical and
      quantum studies based on the reaction path Hamiltonian.
AB  - Electronic structure methods based on density functional theory are used to
      construct a reaction path Hamiltonian for CH4 dissociation on the Ni(100) and
      Ni(111) surfaces. Both quantum and quasi-classical trajectory approaches are used
      to compute dissociative sticking probabilities, including all molecular degrees
      of freedom and the effects of lattice motion. Both approaches show a large
      enhancement in sticking when the incident molecule is vibrationally excited, and
      both can reproduce the mode specificity observed in experiments. However, the
      quasi-classical calculations significantly overestimate the ground state
      dissociative sticking at all energies, and the magnitude of the enhancement in
      sticking with vibrational excitation is much smaller than that computed using the
      quantum approach or observed in the experiments. The origin of this behavior is
      an unphysical flow of zero point energy from the nine normal vibrational modes
      into the reaction coordinate, giving large values for reaction at energies below
      the activation energy. Perturbative assumptions made in the quantum studies are
      shown to be accurate at all energies studied. 

PMID- 24320339
TI  - Solid-solid collapse transition in a two dimensional model molecular system.
AB  - Solid-solid collapse transition in open framework structures is ubiquitous in
      nature. The real difficulty in understanding detailed microscopic aspects of such
      transitions in molecular systems arises from the interplay between different
      energy and length scales involved in molecular systems, often mediated through a
      solvent. In this work we employ Monte-Carlo simulation to study the collapse
      transition in a model molecular system interacting via both isotropic as well as
      anisotropic interactions having different length and energy scales. The model we
      use is known as Mercedes-Benz (MB), which, for a specific set of parameters,
      sustains two solid phases: honeycomb and oblique. In order to study the
      temperature induced collapse transition, we start with a metastable honeycomb
      solid and induce transition by increasing temperature. High density oblique solid
      so formed has two characteristic length scales corresponding to isotropic and
      anisotropic parts of interaction potential. Contrary to the common belief and
      classical nucleation theory, interestingly, we find linear strip-like nucleating
      clusters having significantly different order and average coordination number
      than the bulk stable phase. In the early stage of growth, the cluster grows as a
      linear strip, followed by branched and ring-like strips. The geometry of growing
      cluster is a consequence of the delicate balance between two types of
      interactions, which enables the dominance of stabilizing energy over
      destabilizing surface energy. The nucleus of stable oblique phase is wetted by
      intermediate order particles, which minimizes the surface free energy. In the
      case of pressure induced transition at low temperature the collapsed state is a
      disordered solid. The disordered solid phase has diverse local quasi-stable
      structures along with oblique-solid like domains. 

PMID- 24320340
TI  - Quantitative interpretation of the transition voltages in gold-poly(phenylene)
      thiol-gold molecular junctions.
AB  - The transition voltage of three different asymmetric Au/poly(phenylene) thiol/Au
      molecular junctions in which the central molecule is either benzene thiol,
      biphenyl thiol, or terphenyl thiol is investigated by first-principles quantum
      transport simulations. For all the junctions, the calculated transition voltage
      at positive polarity is in quantitative agreement with the experimental values
      and shows weak dependence on alterations of the Au-phenyl contact. When compared
      to the strong coupling at the Au-S contact, which dominates the alignment of
      various molecular orbitals with respect to the electrode Fermi level, the
      coupling at the Au-phenyl contact produces only a weak perturbation. Therefore,
      variations of the Au-phenyl contact can only have a minor influence on the
      transition voltage. These findings not only provide an explanation to the
      uniformity in the transition voltages found for pi-conjugated molecules measured
      with different experimental methods, but also demonstrate the advantage of
      transition voltage spectroscopy as a tool for determining the positions of
      molecular levels in molecular devices. 

PMID- 24320341
TI  - Multivalent ion screening of charged glass surface studied by streaming potential
      measurements.
AB  - We used streaming potential technique to measure zeta potentials for glass as a
      function of Co(NH3)6Cl3 concentration, KCl concentration, and pH. Charge
      inversion was observed only at high surface charge densities and was inhibited by
      increased KCl concentration. Measured zeta potentials were compared with
      predictions from a recent theory by dos Santos et al. [J. Chem. Phys. 132, 104105
      (2010)] that models multivalent ions adsorbed to the charged surface as a strong
      coupled liquid (SCL). The location of shear plane was determined independent of
      the SCL theory, allowing a rigorous experimental test of the theory with no
      fitting parameters. We found that SCL predictions agree quantitatively with our
      experimental data. 

PMID- 24320342
TI  - A hybrid perturbed-chain SAFT density functional theory for representing fluid
      behavior in nanopores: mixtures.
AB  - The perturbed-chain statistical associating fluid theory (PC-SAFT) density
      functional theory developed in our previous work was extended to the description
      of inhomogeneous confined behavior in nanopores for mixtures. In the developed
      model, the modified fundamental measure theory and the weighted density
      approximation were used to represent the hard-sphere and dispersion free energy
      functionals, respectively, and the chain free energy functional from interfacial
      statistical associating fluid theory was used to account for the chain
      connectivity. The developed model was verified by comparing the model prediction
      with molecular simulation results, and the agreement reveals the reliability of
      the proposed model in representing the confined behaviors of chain mixtures in
      nanopores. The developed model was further used to predict the adsorption of
      methane-carbon dioxide mixtures on activated carbons, in which the parameters of
      methane and carbon dioxide were taken from the bulk PC-SAFT and those for solid
      surface were determined from the fitting to the pure-gas adsorption isotherms
      measured experimentally. The comparison of the model prediction with the
      available experimental data of mixed-gas adsorption isotherms shows that the
      model can reliably reproduce the confined behaviors of physically existing
      mixtures in nanopores. 

PMID- 24320343
TI  - Properties of the low-spin high-spin interface during the relaxation of spin
      crossover materials, investigated through an electro-elastic model.
AB  - The present work is devoted to the spatio-temporal investigations of spin
      crossover lattices during their thermal relaxation from high- to low-spin state.
      The analysis is performed using Monte Carlo simulations on a distortable 2D
      lattice the sites of which are occupied by high-spin (HS) or low-spin (LS) atoms.
      The lattice is circular in shape and the HS to LS transformation results in
      single domain nucleation followed by growth and propagation processes. The
      evolution of the LS:HS interface is monitored during the relaxation process,
      through the mapping of spin states, displacement fields, local stresses, and
      elastic energy. The results show a curved interface, the curvature of which is
      reversed at the mid-transformation. The local stresses and elastic energy peak at
      the vicinity of the HS:LS interface, with sizeable dependence upon the position
      along the front line which evidences the edge effects. 

PMID- 24320344
TI  - Controllable atomistic graphene oxide model and its application in hydrogen
      sulfide removal.
AB  - The determination of an atomistic graphene oxide (GO) model has been challenging
      due to the structural dependence on different synthesis methods. In this work we
      combine temperature-programmed molecular dynamics simulation techniques and the
      ReaxFF reactive force field to generate realistic atomistic GO structures. By
      grafting a mixture of epoxy and hydroxyl groups to the basal graphene surface and
      fine-tuning their initial concentrations, we produce in a controllable manner the
      GO structures with different functional groups and defects. The models agree with
      structural experimental data and with other ab initio quantum calculations. Using
      the generated atomistic models, we perform reactive adsorption calculations for
      H2S and H2O/H2S mixtures on GO materials and compare the results with experiment.
      We find that H2S molecules dissociate on the carbonyl functional groups, and H2O,
      CO2, and CO molecules are released as reaction products from the GO surface. The
      calculation reveals that for the H2O/H2S mixtures, H2O molecules are
      preferentially adsorbed to the carbonyl sites and block the potential active
      sites for H2S decomposition. The calculation agrees well with the experiments.
      The methodology and the procedure applied in this work open a new door to the
      theoretical studies of GO and can be extended to the research on other amorphous
      materials. 

PMID- 24320345
TI  - Adsorption configurations and scanning voltage determined STM images of small
      hydrogen clusters on bilayer graphene.
AB  - By density functional theory calculations, the scanning tunneling microscopy
      (STM) images of various hydrogen clusters adsorbed on bilayer-graphene are
      systematically simulated. The hydrogen configurations of the STM images observed
      in the experiments have been thoroughly figured out. In particular, two kinds of
      hydrogen dimers (ortho-dimer, para-dimer) and two kinds of tetramers (tetramer-A,
      -B) are determined to be the hydrogen configurations corresponding to the
      ellipsoidal-like STM images with different structures and sizes. One particular
      hexamer (hexamer-B) is the hydrogen configuration generating the star-like STM
      images. For each hydrogen cluster, the simulated STM images show unique voltage
      dependent features, which provides a feasible way to determine hydrogen
      adsorption states on graphene or graphite surface in the experiments by varying
      voltage measurements. Stability analysis proves that the above determined
      hydrogen configurations are quite stable on graphene, hence they are likely to be
      detected in the STM experiments. Consequently, through systematic analysis of the
      STM images and the stability of hydrogen clusters on bilayer graphene, many
      experimental observations have been consistently explained. 

PMID- 24320346
TI  - Adsorption and dissociation of oxygen molecules on Si(111)-(7*7) surface.
AB  - The adsorption and dissociation of O2 molecules on Si(111)-(7*7) surface have
      been studied by first-principles calculations. Our results show that all the O2
      molecular species adsorbed on Si(111)-(7*7) surface are unstable and dissociate
      into atomic species with a small energy barrier about 0.1 eV. The single O2
      molecule adsorption tends to form an ins*2 or a new metastable ins*2* structure
      on the Si adatom sites and the further coming O2 molecules adsorb on those
      structures to produce an ad-ins*3 structure. The ad-ins*3 structure is indeed
      highly stable and kinetically limited for diving into the subsurface layer to
      form the ins*3-tri structure by a large barrier of 1.3 eV. Unlike the previous
      views, we find that all the ad-ins, ins*2, and ad-ins*3 structures show bright
      images, while the ins*2*, ins*3, and ins*3-tri structures show dark images. The
      proposed oxidation pathways and simulated scanning tunneling microscope images
      account well for the experimental results and resolve the long-standing confusion
      and issue about the adsorption and reaction of O2 molecules on Si(111) surface. 

PMID- 24320347
TI  - Simulations of solid-liquid friction at ice-I(h)/water interfaces.
AB  - We have investigated the structural and dynamic properties of the basal and
      prismatic facets of the ice Ih/water interface when the solid phase is drawn
      through the liquid (i.e., sheared relative to the fluid phase). To impose the
      shear, we utilized a velocity-shearing and scaling approach to reverse non
      equilibrium molecular dynamics. This method can create simultaneous temperature
      and velocity gradients and allow the measurement of transport properties at
      interfaces. The interfacial width was found to be independent of the relative
      velocity of the ice and liquid layers over a wide range of shear rates. Decays of
      molecular orientational time correlation functions gave similar estimates for the
      width of the interfaces, although the short- and longer-time decay components
      behave differently closer to the interface. Although both facets of ice are in
      "stick" boundary conditions in liquid water, the solid-liquid friction
      coefficients were found to be significantly different for the basal and prismatic
      facets of ice. 

PMID- 24320348
TI  - Ionic density distributions near the charged colloids: spherical electric double
      layers.
AB  - We have studied the structure of the spherical electric double layers on charged
      colloids by a density functional perturbation theory, which is based both on the
      modified fundamental-measure theory for the hard spheres and on the one-particle
      direct correlation functional (DCF) for the electronic residual contribution. The
      contribution of one-particle DCF has been approximated as the functional
      integration of the second-order correlation function of the ionic fluids in a
      bulk phase. The calculated result is in very good agreement with the computer
      simulations for the ionic density distributions and the zeta potentials over a
      wide range of macroion sizes and electrolyte concentrations, and compares with
      the results of Yu et al. [J. Chem. Phys. 120, 7223 (2004)] and modified Poisson
      Boltzmann approximation [L. B. Bhuiyan and C. W. Outhwaite, Condens. Matter Phys.
      8, 287 (2005)]. The present theory is able to provide interesting insights about
      the charge inversion phenomena occurring at the interface. 

PMID- 24320349
TI  - Surface-induced liquid-gas transition in salt-free solutions of model charged
      colloids.
AB  - We report a novel phenomenon of a surface-induced phase transition in salt-free
      solutions of charged colloids. We develop a theory of this effect and confirm it
      by Molecular Dynamics simulations. To describe the colloidal solution we apply a
      primitive model of electrolyte with a strong asymmetry of charge and size of the
      constituent particles - macroions and counterions. To quantify interactions of
      the colloidal particles with the neutral substrate we use a short-range potential
      which models dispersion van der Waals forces. These forces cause the attraction
      of colloids to the surface. We show that for high temperatures and weak
      attraction, only gradual increase of the macroion concentration in the near
      surface layer is observed with increase of interaction strength. If however
      temperature drops below some threshold value, a new dense (liquid) phase is
      formed in the near-surface layer. It can be interpreted as a surface-induced
      first-order phase transition with a critical point. Using an appropriately
      adopted Maxwell construction, we find the binodal. Interestingly, the observed
      near-surface phase transition can occur at the absence of the bulk phase
      transition and may be seemingly classified as prewetting transition. The reported
      effect could be important for various technological applications where formation
      of colloidal particle layers with the desired properties is needed. 

PMID- 24320350
TI  - Phase separation of mixed polymer brushes on surfaces with nonuniform curvature.
AB  - Using numerical simulations and a simple scaling theory, we study the microphase
      separation of a mixture of polymer brushes with different chain lengths tethered
      to surfaces with nonuniform curvature. We measure the free energy difference of
      the phase separated configurations as a function of spheroid eccentricity and
      ordering of the microdomains formed on them. We find that there is a preference
      for the longer chains to locate in high curvature regions, and identify and
      quantify the driving forces associated with this phenomenon. We also find that
      nonuniform curvature typically limits the number of striped domains that would
      normally form on a spherical surface under identical physical conditions.
      Finally, we generalize the scaling theory developed for brushes on spherical
      surfaces to include prolate and oblate spheroids, and show explicitly that while
      immiscibility between the chains is required for phase separation to occur on
      spheroids, it is unnecessary for certain surfaces with regions of positive and
      negative curvature. We present a phase diagram showing the conditions under which
      curvature-driven phase separation of miscible, but lengthwise asymmetric chains
      is expected to occur. 

PMID- 24320351
TI  - Kinetics of lamellar formation on sparsely stripped patterns.
AB  - Chemical epitaxy based on the self-assembly of block copolymers is viewed as a
      promising technique to achieve ordered patterns on a large scale. Herein, we
      study the kinetics of lamellar formation of block copolymers under the direction
      of sparsely stripped patterns using cell dynamics simulations of the time
      dependent Ginzburg-Landau theory. First, a scaling law is unveiled with the
      ordering time of lamellae, tp, with respect to the multiples between the periods
      of lamellae and stripe patterns, which is consistent with the power law evolution
      of the correlation length existing in the bulk phase of lamellae. Second, the
      tolerative windows of perfect order, with deviation from integer multiples, are
      also estimated from the aspect of kinetics. The results of the ordering time and
      tolerative windows are of great interest for relevant experiments or
      applications. Finally, a two-stage evolution is explored during the pattern
      formation of chemical epitaxy by probing into the evolution of defects, which is
      of fundamental interest for us to understand the coarsening kinetics of block
      copolymers under the direction of chemical patterns. 

PMID- 24320352
TI  - Computational study of imperfect networks using a coarse-grained model.
AB  - The structural and mechanical properties of imperfect entangled polymer networks
      with various fractions of elastically active chains are studied using a generic
      coarse-grained model. Network topology is analyzed at various degrees of cross
      linking and correlated with the mechanical response under uniaxial deformation at
      various strain rates. We found excellent agreement between results obtained from
      the structural analysis and from fitting to stress relaxation data. The
      relaxation tensile modulus at various engineering strains was also calculated as
      a function of the fraction of active strands. Results indicate that the
      mechanical and viscoelastic properties of entangled polymer networks are
      susceptible to variation in the network structure, where defects can affect the
      mechanical response especially at low strain rates and the relaxation behavior at
      long times. 

PMID- 24320353
TI  - On the theory of double quantum NMR in polymer systems: the second cumulant
      approximation for many spin I = 1/2 systems.
AB  - General analytical expressions for Double Quantum Nuclear Magnetic Resonance (DQ
      NMR) kinetic curves of many-spin I = 1/2 systems are derived with an accuracy of
      the second cumulant approximation. The expressions obtained exactly describe the
      initial part of the kinetic curves and provide a reasonable approximation up to
      times of about the effective spin-relaxation time. For the case when the system
      contains two isolated spins, this result exactly reproduces known expressions. In
      the case of polymer melts, the intermolecular magnetic dipole-dipole interactions
      significantly influence the time dependence of the DQ NMR kinetic curves. 

PMID- 24320354
TI  - Note: on the relation between Lifson-Jackson and Derrida formulas for effective
      diffusion coefficient.

PMID- 24320356
TI  - Communication: The correct interpretation of surface hopping trajectories: how to
      calculate electronic properties.
AB  - In a recent paper, we presented a road map for how Tully's fewest switches
      surface hopping (FSSH) algorithm can be derived, under certain circumstances,
      from the mixed quantum-classical Liouville equation. In this communication, we
      now demonstrate how this new interpretation of surface hopping can yield
      significantly enhanced results for electronic properties in nonadiabatic
      calculations. Specifically, we calculate diabatic populations for the spin-boson
      problem using FSSH trajectories. We show that, for some Hamiltonians, without
      changing the FSSH algorithm at all but rather simply reinterpreting the ensemble
      of surface hopping trajectories, we recover excellent results and remove any and
      all ambiguity about the initial condition problem. 

PMID- 24320357
TI  - Communication: A reduced-space algorithm for the solution of the complex linear
      response equations used in coupled cluster damped response theory.
AB  - We present a reduced-space algorithm for solving the complex (damped) linear
      response equations required to compute the complex linear response function for
      the hierarchy of methods: coupled cluster singles, coupled cluster singles and
      iterative approximate doubles, and coupled cluster singles and doubles. The
      solver is the keystone element for the development of damped coupled cluster
      response methods for linear and nonlinear effects in resonant frequency regions. 

PMID- 24320358
TI  - Modeling and enhanced sampling of molecular systems with smooth and nonlinear
      data-driven collective variables.
AB  - Collective variables (CVs) are low-dimensional representations of the state of a
      complex system, which help us rationalize molecular conformations and sample free
      energy landscapes with molecular dynamics simulations. Given their importance,
      there is need for systematic methods that effectively identify CVs for complex
      systems. In recent years, nonlinear manifold learning has shown its ability to
      automatically characterize molecular collective behavior. Unfortunately, these
      methods fail to provide a differentiable function mapping high-dimensional
      configurations to their low-dimensional representation, as required in enhanced
      sampling methods. We introduce a methodology that, starting from an ensemble
      representative of molecular flexibility, builds smooth and nonlinear data-driven
      collective variables (SandCV) from the output of nonlinear manifold learning
      algorithms. We demonstrate the method with a standard benchmark molecule, alanine
      dipeptide, and show how it can be non-intrusively combined with off-the-shelf
      enhanced sampling methods, here the adaptive biasing force method. We illustrate
      how enhanced sampling simulations with SandCV can explore regions that were
      poorly sampled in the original molecular ensemble. We further explore the
      transferability of SandCV from a simpler system, alanine dipeptide in vacuum, to
      a more complex system, alanine dipeptide in explicit water. 

PMID- 24320359
TI  - Extended Lagrangian Born-Oppenheimer molecular dynamics in the limit of vanishing
      self-consistent field optimization.
AB  - We present an efficient general approach to first principles molecular dynamics
      simulations based on extended Lagrangian Born-Oppenheimer molecular dynamics [A.
      M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] in the limit of vanishing
      self-consistent field optimization. The reduction of the optimization requirement
      reduces the computational cost to a minimum, but without causing any significant
      loss of accuracy or long-term energy drift. The optimization-free first
      principles molecular dynamics requires only one single diagonalization per time
      step, but is still able to provide trajectories at the same level of accuracy as
      "exact," fully converged, Born-Oppenheimer molecular dynamics simulations. The
      optimization-free limit of extended Lagrangian Born-Oppenheimer molecular
      dynamics therefore represents an ideal starting point for robust and efficient
      first principles quantum mechanical molecular dynamics simulations. 

PMID- 24320360
TI  - Linear-scaling calculation of Hartree-Fock exchange energy with non-orthogonal
      generalised Wannier functions.
AB  - We present a method for the calculation of four-centre two-electron repulsion
      integrals in terms of localised non-orthogonal generalised Wannier functions
      (NGWFs). Our method has been implemented in the ONETEP program and is used to
      compute the Hartree-Fock exchange energy component of Hartree-Fock and Density
      Functional Theory (DFT) calculations with hybrid exchange-correlation
      functionals. As the NGWFs are optimised in situ in terms of a systematically
      improvable basis set which is equivalent to plane waves, it is possible to
      achieve large basis set accuracy in routine calculations. The spatial
      localisation of the NGWFs allows us to exploit the exponential decay of the
      density matrix in systems with a band gap in order to compute the exchange energy
      with a computational effort that increases linearly with the number of atoms. We
      describe the implementation of this approach in the ONETEP program for linear
      scaling first principles quantum mechanical calculations. We present extensive
      numerical validation of all the steps in our method. Furthermore, we find
      excellent agreement in energies and structures for a wide variety of molecules
      when comparing with other codes. We use our method to perform calculations with
      the B3LYP exchange-correlation functional for models of myoglobin systems bound
      with O2 and CO ligands and confirm that the same qualitative behaviour is
      obtained as when the same myoglobin models are studied with the DFT+U approach
      which is also available in ONETEP. Finally, we confirm the linear-scaling
      capability of our method by performing calculations on polyethylene and
      polyacetylene chains of increasing length. 

PMID- 24320361
TI  - An improved fragment-based quantum mechanical method for calculation of
      electrostatic solvation energy of proteins.
AB  - An efficient approach that combines the electrostatically embedded generalized
      molecular fractionation with conjugate caps (EE-GMFCC) method with conductor-like
      polarizable continuum model (CPCM), termed EE-GMFCC-CPCM, is developed for ab
      initio calculation of the electrostatic solvation energy of proteins. Compared
      with the previous MFCC-CPCM study [Y. Mei, C. G. Ji, and J. Z. H. Zhang, J. Chem.
      Phys. 125, 094906 (2006)], quantum mechanical (QM) calculation is applied to deal
      with short-range non-neighboring interactions replacing the classical treatment.
      Numerical studies are carried out for proteins up to 3837 atoms at the HF/6-31G*
      level. As compared to standard full system CPCM calculations, EE-GMFCC-CPCM shows
      clear improvement over the MFCC-CPCM method for both the total electrostatic
      solvation energy and its components (the polarized solute-solvent reaction field
      energy and wavefunction distortion energy of the solute). For large proteins with
      1000-4000 atoms, where the standard full system ab initio CPCM calculations are
      not affordable, the EE-GMFCC-CPCM gives larger relative wavefunction distortion
      energies and weaker relative electrostatic solvation energies for proteins, as
      compared to the corresponding energies calculated by the Divide-and-Conquer
      Poisson-Boltzmann (D&C-PB) method. Notwithstanding, a high correlation between EE
      GMFCC-CPCM and D&C-PB is observed. This study demonstrates that the linear
      scaling EE-GMFCC-CPCM approach is an accurate and also efficient method for the
      calculation of electrostatic solvation energy of proteins.

PMID- 24320362
TI  - Hamilton-Jacobi method for molecular distribution function in a chemical
      oscillator.
AB  - Using the Hamilton-Jacobi method, we solve chemical Fokker-Planck equations
      within the Gaussian approximation and obtain a simple and compact formula for a
      conditional probability distribution. The formula holds in general transient
      situations, and can be applied not only to a steady state but also to an
      oscillatory state. By analyzing the long time behavior of the solution in the
      oscillatory case, we obtain the phase diffusion constant along the periodic orbit
      and the steady distribution perpendicular to it. A simple method for numerical
      evaluation of these formulas are devised, and they are compared with Monte Carlo
      simulations in the case of Brusselator as an example. Some results are shown to
      be identical to previously obtained expressions. 

PMID- 24320363
TI  - Resummed thermodynamic perturbation theory for bond cooperativity in associating
      fluids.
AB  - We develop a resummed thermodynamic perturbation theory for bond cooperativity in
      associating fluids by extension of Wertheim's multi-density formalism. We
      specifically consider the case of an associating hard sphere with two association
      sites and both pairwise and triplet contributions to the energy, such that the
      first bond in an associated cluster receives an energy -epsilon((1)) and each
      subsequent bond in the cluster receives an energy -epsilon((2)). To test the
      theory we perform new Monte Carlo simulations for potentials of this type. Theory
      and simulation are found to be in excellent agreement. We show that decreasing
      the energetic benefit of hydrogen bonding can actually result in a decrease in
      internal energy in the fluid. We also predict that when epsilon((1)) = 0 and
      epsilon((2)) is nonzero there is a transition temperature where the system
      transitions from a fluid of monomers to a mixture of monomers and very long
      chains.

PMID- 24320364
TI  - Can we derive Tully's surface-hopping algorithm from the semiclassical quantum
      Liouville equation? Almost, but only with decoherence.
AB  - In this article, we demonstrate that Tully's fewest-switches surface hopping
      (FSSH) algorithm approximately obeys the mixed quantum-classical Liouville
      equation (QCLE), provided that several conditions are satisfied--some major
      conditions, and some minor. The major conditions are: (1) nuclei must be moving
      quickly with large momenta; (2) there cannot be explicit recoherences or
      interference effects between nuclear wave packets; (3) force-based decoherence
      must be added to the FSSH algorithm, and the trajectories can no longer
      rigorously be independent (though approximations for independent trajectories are
      possible). We furthermore expect that FSSH (with decoherence) will be most robust
      when nonadiabatic transitions in an adiabatic basis are dictated primarily by
      derivative couplings that are presumably localized to crossing regions, rather
      than by small but pervasive off-diagonal force matrix elements. In the end, our
      results emphasize the strengths of and possibilities for the FSSH algorithm when
      decoherence is included, while also demonstrating the limitations of the FSSH
      algorithm and its inherent inability to follow the QCLE exactly.

PMID- 24320365
TI  - Time dependent quantum thermodynamics of a coupled quantum oscillator system in a
      small thermal environment.
AB  - Simulations are performed of a small quantum system interacting with a quantum
      environment. The system consists of various initial states of two harmonic
      oscillators coupled to give normal modes. The environment is "designed" by its
      level pattern to have a thermodynamic temperature. A random coupling causes the
      system and environment to become entangled in the course of time evolution. The
      approach to a Boltzmann distribution is observed, and effective fitted
      temperatures close to the designed temperature are obtained. All initial pure
      states of the system are driven to equilibrium at very similar rates, with quick
      loss of memory of the initial state. The time evolution of the von Neumann
      entropy is calculated as a measure of equilibration and of quantum coherence. It
      is pointed out using spatial density distribution plots that quantum interference
      is eliminated only with maximal entropy, which corresponds thermally to infinite
      temperature. Implications of our results for the notion of "classicalizing"
      behavior in the approach to thermal equilibrium are briefly considered. 

PMID- 24320366
TI  - Efficient basis sets for non-covalent interactions in XDM-corrected density
      functional theory.
AB  - In the development and application of dispersion-corrected density-functional
      theory, the effects of basis set incompleteness have been largely mitigated
      through the use of very large, nearly-complete basis sets. However, the use of
      such large basis sets makes application of these methods inefficient for large
      systems. In this work, we examine a series of basis sets, including Pople-style,
      correlation-consistent, and polarization-consistent bases, for their ability to
      efficiently and accurately predict non-covalent interactions when used in
      conjunction with the exchange-hole dipole moment (XDM) dispersion model. We find
      that the polarization-consistent 2 (pc-2) basis sets, and two modifications
      thereof with some diffuse functions removed, give performance of comparable
      quality to that obtained with aug-cc-pVTZ basis sets, while being roughly 12 to
      23 times faster computationally. The behavior is explained, in part, by the role
      of diffuse functions in recovering small density changes in the intermolecular
      region. The general performance of the modified basis sets is tested by
      application of XDM to standard intermolecular benchmark sets at, and away from,
      equilibrium. 

PMID- 24320367
TI  - Self-consistent continuum solvation (SCCS): the case of charged systems.
AB  - The recently developed self-consistent continuum solvation model (SCCS) [O.
      Andreussi, I. Dabo, and N. Marzari, J. Chem. Phys. 136, 064102 (2012)] is applied
      here to charged species in aqueous solutions. Describing ions in solution
      represents a great challenge because of the large electrostatic interactions
      between the solute and the solvent. The SCCS model is tested over 106 monocharged
      species, both cations and anions, and we demonstrate its flexibility,
      notwithstanding its much reduced set of parameters, to describe charged species
      in solution. Remarkably low mean absolute errors are obtained with values of 2.27
      and 5.54 kcal/mol for cations and anions, respectively. These results are
      comparable or better than the state of the art to describe solvation of charged
      species in water. Finally, differences of behavior between cations and anions are
      discussed. 

PMID- 24320368
TI  - Proximal distributions from angular correlations: a measure of the onset of
      coarse-graining.
AB  - In this work we examine and extend the theory of proximal radial distribution
      functions for molecules in solution. We point out two formal extensions, the
      first of which generalizes the proximal distribution function hierarchy approach
      to the complete, angularly dependent molecular pair distribution function.
      Second, we generalize from the traditional right-handed solute-solvent proximal
      distribution functions to the left-handed distributions. The resulting neighbor
      hierarchy convergence is shown to provide a measure of the coarse-graining of the
      internal solute sites with respect to the solvent. Simulation of the test case of
      a deca-alanine peptide shows that this coarse-graining measure converges at a
      length scale of approximately 5 amino acids for the system considered. 

PMID- 24320369
TI  - A minimally-resolved immersed boundary model for reaction-diffusion problems.
AB  - We develop an immersed boundary approach to modeling reaction-diffusion processes
      in dispersions of reactive spherical particles, from the diffusion-limited to the
      reaction-limited setting. We represent each reactive particle with a minimally
      resolved "blob" using many fewer degrees of freedom per particle than standard
      discretization approaches. More complicated or more highly resolved particle
      shapes can be built out of a collection of reactive blobs. We demonstrate
      numerically that the blob model can provide an accurate representation at low to
      moderate packing densities of the reactive particles, at a cost not much larger
      than solving a Poisson equation in the same domain. Unlike multipole expansion
      methods, our method does not require analytically computed Green's functions, but
      rather, computes regularized discrete Green's functions on the fly by using a
      standard grid-based discretization of the Poisson equation. This allows for great
      flexibility in implementing different boundary conditions, coupling to fluid flow
      or thermal transport, and the inclusion of other effects such as temporal
      evolution and even nonlinearities. We develop multigrid-based preconditioners for
      solving the linear systems that arise when using implicit temporal
      discretizations or studying steady states. In the diffusion-limited case the
      resulting linear system is a saddle-point problem, the efficient solution of
      which remains a challenge for suspensions of many particles. We validate our
      method by comparing to published results on reaction-diffusion in ordered and
      disordered suspensions of reactive spheres. 

PMID- 24320370
TI  - The Stokes-Einstein relation at moderate Schmidt number.
AB  - The Stokes-Einstein relation for the self-diffusion coefficient of a spherical
      particle suspended in an incompressible fluid is an asymptotic result in the
      limit of large Schmidt number, that is, when momentum diffuses much faster than
      the particle. When the Schmidt number is moderate, which happens in most particle
      methods for hydrodynamics, deviations from the Stokes-Einstein prediction are
      expected. We study these corrections computationally using a recently developed
      minimally resolved method for coupling particles to an incompressible fluctuating
      fluid in both two and three dimensions. We find that for moderate Schmidt numbers
      the diffusion coefficient is reduced relative to the Stokes-Einstein prediction
      by an amount inversely proportional to the Schmidt number in both two and three
      dimensions. We find, however, that the Einstein formula is obeyed at all Schmidt
      numbers, consistent with linear response theory. The mismatch arises because
      thermal fluctuations affect the drag coefficient for a particle due to the
      nonlinear nature of the fluid-particle coupling. The numerical data are in good
      agreement with an approximate self-consistent theory, which can be used to
      estimate finite-Schmidt number corrections in a variety of methods. Our results
      indicate that the corrections to the Stokes-Einstein formula come primarily from
      the fact that the particle itself diffuses together with the momentum. Our study
      separates effects coming from corrections to no-slip hydrodynamics from those of
      finite separation of time scales, allowing for a better understanding of widely
      observed deviations from the Stokes-Einstein prediction in particle methods such
      as molecular dynamics. 

PMID- 24320371
TI  - Spin-free Dirac-Coulomb calculations augmented with a perturbative treatment of
      spin-orbit effects at the Hartree-Fock level.
AB  - A perturbative approach to compute second-order spin-orbit (SO) corrections to a
      spin-free Dirac-Coulomb Hartree-Fock (SFDC-HF) calculation is suggested. The
      proposed scheme treats the difference between the DC and SFDC Hamiltonian as
      perturbation and exploits analytic second-derivative techniques. In addition, a
      cost-effective scheme for incorporating relativistic effects in high-accuracy
      calculations is suggested consisting of a SFDC coupled-cluster treatment
      augmented by perturbative SO corrections obtained at the HF level. Benchmark
      calculations for the hydrogen halides HX, X = F-At as well as the coinage-metal
      fluorides CuF, AgF, and AuF demonstrate the accuracy of the proposed perturbative
      treatment of SO effects on energies and electrical properties in comparison with
      the more rigorous full DC treatment. Furthermore, we present, as an application
      of our scheme, results for the electrical properties of AuF and XeAuF. 

PMID- 24320372
TI  - Diffusion in narrow channels on curved manifolds.
AB  - In this work, we derive a general effective diffusion coefficient to describe the
      two-dimensional (2D) diffusion in a narrow and smoothly asymmetric channel of
      varying width, embedded on a curved surface, in the simple diffusion of non
      interacting, point-like particles under no external field. To this end, we extend
      the generalization of the Kalinay-Percus' projection method [J. Chem. Phys. 122,
      204701 (2005); Phys. Rev. E 74, 041203 (2006)] for the asymmetric channels
      introduced in [L. Dagdug and I. Pineda, J. Chem. Phys. 137, 024107 (2012)], to
      project the anisotropic two-dimensional diffusion equation on a curved manifold,
      into an effective one-dimensional generalized Fick-Jacobs equation that is
      modified according to the curvature of the surface. For such purpose we construct
      the whole expansion, writing the marginal concentration as a perturbation series.
      The lowest order in the perturbation parameter, which corresponds to the Fick
      Jacobs equation, contains an additional term that accounts for the curvature of
      the surface. We explicitly obtain the first-order correction for the invariant
      effective concentration, which is defined as the correct marginal concentration
      in one variable, and we obtain the first approximation to the effective diffusion
      coefficient analogous to Bradley's coefficient [Phys. Rev. E 80, 061142 (2009)]
      as a function of the metric elements of the surface. In a straightforward manner,
      we study the perturbation series up to the nth order, and derive the full
      effective diffusion coefficient for two-dimensional diffusion in a narrow
      asymmetric channel, with modifications according to the metric terms. This
      expression is given as
      D(xi)=D(0)/w'(xi)?(g(1)/g(2)){arctan[?(g(2)/g(1))(y(0)'(xi)+w'(xi)/2)]
      arctan[?(g(2)/g(1))(y(0)'(xi)-w'(xi)/2)]}, which is the main result of our work.
      Finally, we present two examples of symmetric surfaces, namely, the sphere and
      the cylinder, and we study certain specific channel configurations on these
      surfaces.

PMID- 24320374
TI  - Shape resonances in low-energy-electron collisions with halopyrimidines.
AB  - We report calculated cross sections for elastic collisions of low-energy
      electrons with halopyrimidines, namely, 2-chloro, 2-bromo, and 5-bromopyrimidine.
      We employed the Schwinger multichannel method with pseudopotentials to compute
      the cross sections in the static-exchange and static-exchange plus polarization
      levels of approximation for energies up to 10 eV. We found four shape resonances
      for each molecule: three of pi* nature localized on the ring and one of sigma*
      nature localized along the carbon-halogen bond. We compared the calculated
      positions of the resonances with the electron transmission spectroscopy data
      measured by Modelli et al. [J. Phys. Chem. A 115, 10775 (2011)]. In general the
      agreement between theory and experiment is good. In particular, our results show
      the existence of a pi* temporary anion state of A2 symmetry for all three
      halopyrimidines, in agreement with the dissociative electron attachment spectra
      also reported by Modelli et al. [J. Phys. Chem. A 115, 10775 (2011)].

PMID- 24320373
TI  - Observation of strongly forbidden solid effect dynamic nuclear polarization
      transitions via electron-electron double resonance detected NMR.
AB  - We present electron paramagnetic resonance experiments for which solid effect
      dynamic nuclear polarization transitions were observed indirectly via
      polarization loss on the electron. This use of indirect observation allows
      characterization of the dynamic nuclear polarization (DNP) process close to the
      electron. Frequency profiles of the electron-detected solid effect obtained using
      trityl radical showed intense saturation of the electron at the usual solid
      effect condition, which involves a single electron and nucleus. However, higher
      order solid effect transitions involving two, three, or four nuclei were also
      observed with surprising intensity, although these transitions did not lead to
      bulk nuclear polarization--suggesting that higher order transitions are important
      primarily in the transfer of polarization to nuclei nearby the electron. Similar
      results were obtained for the SA-BDPA radical where strong electron-nuclear
      couplings produced splittings in the spectrum of the indirectly observed solid
      effect conditions. Observation of high order solid effect transitions supports
      recent studies of the solid effect, and suggests that a multi-spin solid effect
      mechanism may play a major role in polarization transfer via DNP.

PMID- 24320375
TI  - Simulation of femtosecond "double-slit" experiments for a chromophore in a
      dissipative environment.
AB  - We performed simulations of the prototypical femtosecond "double-slit" experiment
      with strong pulsed laser fields for a chromophore in solution. The chromophore is
      modeled as a system with two electronic levels and a single Franck-Condon active
      underdamped vibrational mode. All other (intra- and inter-molecular) vibrational
      modes are accounted for as a thermal bath. The system-bath coupling is treated in
      a computationally accurate manner using the hierarchy equations of motion
      approach. The double-slit signal is evaluated numerically exactly without
      invoking perturbation theory in the matter-field interaction. We show that the
      strong-pulse double-slit signal consists of a superposition of N-wave-mixing (N =
      2, 4, 6...) responses and can be split into population and coherence
      contributions. The former reveals the dynamics of vibrational wave packets in the
      ground state and the excited electronic state of the chromophore, while the
      latter contains information on the dephasing of electronic coherences of the
      chromophore density matrix. We studied the influence of heat baths with different
      coupling strengths and memories on the double-slit signal. Our results show that
      the double-slit experiment performed with strong (nonperturbative) pulses yields
      substantially more information on the photoinduced dynamics of the chromophore
      than the weak-pulse experiment, in particular, if the bath-induced dephasings are
      fast.

PMID- 24320376
TI  - Thermal decomposition products of butyraldehyde.
AB  - The thermal decomposition of gas-phase butyraldehyde, CH3CH2CH2CHO, was studied
      in the 1300-1600 K range with a hyperthermal nozzle. Products were identified via
      matrix-isolation Fourier transform infrared spectroscopy and photoionization mass
      spectrometry in separate experiments. There are at least six major initial
      reactions contributing to the decomposition of butyraldehyde: a radical
      decomposition channel leading to propyl radical + CO + H; molecular elimination
      to form H2 + ethylketene; a keto-enol tautomerism followed by elimination of H2O
      producing 1-butyne; an intramolecular hydrogen shift and elimination producing
      vinyl alcohol and ethylene, a beta-C-C bond scission yielding ethyl and vinoxy
      radicals; and a gamma-C-C bond scission yielding methyl and CH2CH2CHO radicals.
      The first three reactions are analogous to those observed in the thermal
      decomposition of acetaldehyde, but the latter three reactions are made possible
      by the longer alkyl chain structure of butyraldehyde. The products identified
      following thermal decomposition of butyraldehyde are CO, HCO, CH3CH2CH2,
      CH3CH2CH=C=O, H2O, CH3CH2C=CH, CH2CH2, CH2=CHOH, CH2CHO, CH3, HC=CH, CH2CCH,
      CH3C=CH, CH3CH=CH2, H2C=C=O, CH3CH2CH3, CH2=CHCHO, C4H2, C4H4, and C4H8. The
      first ten products listed are direct products of the six reactions listed above.
      The remaining products can be attributed to further decomposition reactions or
      bimolecular reactions in the nozzle.

PMID- 24320377
TI  - Solvent effects on the ultrafast nonradiative deactivation mechanisms of thymine
      in aqueous solution: excited-state QM/MM molecular dynamics simulations.
AB  - On-the-fly excited-state quantum mechanics/molecular mechanics molecular dynamics
      (QM/MM-MD) simulations of thymine in aqueous solution are performed to
      investigate the role of solvent water molecules on the nonradiative deactivation
      process. The complete active space second-order perturbation theory (CASPT2)
      method is employed for a thymine molecule as the QM part in order to provide a
      reliable description of the excited-state potential energies. It is found that,
      in addition to the previously reported deactivation pathway involving the
      twisting of the C-C double bond in the pyrimidine ring, another efficient
      deactivation pathway leading to conical intersections that accompanies the out-of
      plane displacement of the carbonyl group is observed in aqueous solution. Decay
      through this pathway is not observed in the gas phase simulations, and our
      analysis indicates that the hydrogen bonds with solvent water molecules play a
      key role in stabilizing the potential energies of thymine in this additional
      decay pathway.

PMID- 24320378
TI  - Theoretical study of Al(n)V+ clusters and their interaction with Ar.
AB  - Recently, it has been experimentally elucidated whether a V impurity in Al(n)V(+)
      clusters occupies an external or an internal site by studying their interaction
      with argon as a function of cluster size [S. M. Lang, P. Claes, S. Neukermans,
      and E. Janssens, J. Am. Soc. Mass Spectrom. 22, 1508 (2011)]. In the work
      presented here we studied, by means of density functional theoretic calculations,
      the structural and electronic properties of Al(n)V(+) clusters with n = 14-21
      atoms, as well as the adsorption of a single Ar atom on them. For n < 17 the
      lowest energy structure of Al(n)V(+) is related to that of the pure Al(n+1)(+)
      cluster with the V atom substituting a surface Al atom. For n >= 17 the V
      impurity becomes embedded in the cluster, in agreement with the experimental
      results, and the clusters adopt a fcc-like structure instead of the icosahedral
      like skeleton of pure Al(n+1)(+). We have studied the binding energy per atom,
      the second energy difference, and the V and Al atom separation energies, in
      comparison with those of pure Al(n+1)(+). We also studied the adsorption of
      atomic Ar on endohedral and exohedral V doped clusters. The optimized Ar
      adsorption geometries are formed with Ar on top of a surface atom (V for n < 17,
      and Al for n >= 17) without noticeable structural distortion of the host cluster.
      At the critical size (n = 17) of the exohedral-endohedral transition, the
      calculated Ar adsorption energy exhibits a drop and the Ar-cluster distance
      increases drastically, indicating that Ar becomes physisorbed rather than
      chemisorbed. All these results confirm the assumptions made by the
      experimentalists when interpreting their measurements.

PMID- 24320379
TI  - Non-Markovian response of ultrafast coherent electronic ring currents in chiral
      aromatic molecules in a condensed phase.
AB  - Results of a theoretical study on non-Markov response for femtosecond laser
      driven coherent ring currents in chiral aromatic molecules embedded in a
      condensed phase are presented. Coherent ring currents are generated by coherent
      excitation of a pair of quasi-degenerated pi-electronic excited states. The
      coherent electronic dynamical behaviors are strongly influenced by interactions
      between the electronic system and phonon bath in a condensed phase. Here, the
      bath correlation time is not instantaneous but should be taken to be a finite
      time in ultrashort time-resolved experiments. In such a case, Markov
      approximation breaks down. A hierarchical master equation approach for an
      improved semiclassical Drude dissipation model was adopted to examine the non
      Markov effects on ultrafast coherent electronic ring currents of (P)-2,2'
      biphenol in a condensed phase. Time evolution of the coherent ring current
      derived in the hierarchical master equation approach was calculated and compared
      with those in the Drude model in the Markov approximation and in the static
      limit. The results show how non-Markovian behaviors in quantum beat signals of
      ring currents depend on the Drude bath damping constant. Effects of temperatures
      on ultrafast coherent electronic ring currents are also clarified.

PMID- 24320380
TI  - Trends in alkali metal hydrosulfides: a combined Fourier transform
      microwave/millimeter-wave spectroscopic study of KSH (X1A').
AB  - The pure rotational spectrum of KSH (X(1)A') has been measured using millimeter
      wave direct absorption and Fourier transform microwave (FTMW) techniques. This
      work is the first gas-phase experimental study of this molecule and includes
      spectroscopy of KSD as well. In the millimeter-wave system, KSH was synthesized
      in a DC discharge from a mixture of potassium vapor, H2S, and argon; a discharge
      assisted laser ablation source, coupled with a supersonic jet expansion, was used
      to create the species in the FTMW instrument. Five and three rotational
      transitions in the range 3-57 GHz were recorded with the FTMW experiment for KSH
      and KSD, respectively, in the K(a) = 0 component; in these data, potassium
      quadrupole hyperfine structure was observed. Five to six transitions with K(a) =
      0-5 were measured in the mm-wave region (260-300 GHz) for the two species. The
      presence of multiple asymmetry components in the mm-wave spectra indicates that
      KSH has a bent geometry, in analogy to other alkali hydrosulfides. The data were
      analyzed with an S-reduced asymmetric top Hamiltonian, and rotational,
      centrifugal distortion, and potassium electric quadrupole coupling constants were
      determined for both isotopolgues. The r0 geometry for KSH was calculated to be
      r(S-H) = 1.357(1) A, r(K-S) = 2.806(1) A, and theta(M-S-H) ( degrees ) = 95.0
      (1). FTMW measurements were also carried out on LiSH and NaSH; metal electric
      quadrupole coupling constants were determined for comparison with KSH. In
      addition, ab initio computations of the structures and vibrational frequencies at
      the CCSD(T)/6-311++G(3df,2pd) and CCSD(T)/aug-cc-pVTZ levels of theory were
      performed for LiSH, NaSH, and KSH. Overall, experimental and computational data
      suggest that the metal-ligand bonding in KSH is a combination of electrostatic
      and covalent forces.

PMID- 24320381
TI  - Energy and charge transfer in ionized argon coated water clusters.
AB  - We investigate the electron ionization of clusters generated in mixed Ar-water
      expansions. The electron energy dependent ion yields reveal the neutral cluster
      composition and structure: water clusters fully covered with the Ar solvation
      shell are formed under certain expansion conditions. The argon atoms shield the
      embedded (H2O)n clusters resulting in the ionization threshold above ~15 eV for
      all fragments. The argon atoms also mediate more complex reactions in the
      clusters: e.g., the charge transfer between Ar(+) and water occurs above the
      threshold; at higher electron energies above ~28 eV, an excitonic transfer
      process between Ar(+)* and water opens leading to new products Ar(n)H(+) and
      (H2O)(n)H(+). On the other hand, the excitonic transfer from the neutral Ar*
      state at lower energies is not observed although this resonant process was
      demonstrated previously in a photoionization experiment. Doubly charged fragments
      (H2O)(n)H2(2+) and (H2O)(n)(2+) ions are observed and Intermolecular Coulomb
      decay (ICD) processes are invoked to explain their thresholds. The Coulomb
      explosion of the doubly charged cluster formed within the ICD process is
      prevented by the stabilization effect of the argon solvent.

PMID- 24320382
TI  - Infrared spectra and tunneling dynamics of the N2-D2O and OC-D2O complexes in the
      v2 bend region of D2O.
AB  - The rovibrational spectra of the N2-D2O and OC-D2O complexes in the v2 bend
      region of D2O have been measured in a supersonic slit jet expansion using a rapid
      scan tunable diode laser spectrometer. Both a-type and b-type transitions were
      observed for these two complexes. All transitions are doubled, due to the heavy
      water tunneling within the complexes. Assuming the tunneling splittings are the
      same in K(a) = 0 and K(a) = 1, the band origins, all three rotational and several
      distortion constants of each tunneling state were determined for N2-D2O in the
      ground and excited vibrational states, and for OC-D2O in the excited vibrational
      state, respectively. The averaged band origin of OC-D2O is blueshifted by 2.241
      cm(-1) from that of the v2 band of the D2O monomer, compared with 1.247 cm(-1)
      for N2-D2O. The tunneling splitting of N2-D2O in the ground state is 0.16359(28)
      cm(-1), which is about five times that of OC-D2O. The tunneling splittings
      decrease by about 26% for N2-D2O and 23% for OC-D2O, respectively, upon
      excitation of the D2O bending vibration, indicating an increase of the tunneling
      barrier in the excited vibrational state. The tunneling splittings are found to
      have a strong dependence on intramolecular vibrational excitation as well as a
      weak dependence on quantum number K(a).

PMID- 24320383
TI  - A new look at the photodissociation of methyl iodide at 193 nm.
AB  - A new measurement of the photodissociation of CH3I at 193 nm is reported in which
      we use a combination of vacuum ultraviolet photoionization and velocity map ion
      imaging. The iodine photofragments are probed by single-photon ionization at
      photon energies above and below the photoionization threshold of I((2)P(3/2)).
      The relative I((2)P(3/2)) and I*((2)P(1/2)) photoionization cross sections are
      determined at these wavelengths by using the known branching fractions for the
      photodissociation at 266 nm. Velocity map ion images indicate that the branching
      fraction for I((2)P(3/2)) atoms is non-zero, and yield a value of 0.07 +/- 0.01.
      Interestingly, the translational energy distribution extracted from the image
      shows that the translational energy of the I((2)P(3/2)) fragments is
      significantly smaller than that of the I*((2)P(1/2)) atoms. This observation
      indicates the internal rotational/vibrational energy of the CH3 co-fragment is
      very high in the I((2)P(3/2)) channel. The results can be interpreted in a manner
      consistent with the previous measurements, and provide a more complete picture of
      the dissociation dynamics of this prototypical molecule.

PMID- 24320384
TI  - Lowest triplet (n,pi*) state of 2-cyclohexen-1-one: characterization by cavity
      ringdown spectroscopy and quantum-chemical calculations.
AB  - The cavity ringdown (CRD) absorption spectrum of 2-cyclohexen-1-one (2CHO) was
      recorded over the range 401.5-410.5 nm in a room-temperature gas cell. The very
      weak band system (epsilon <= 0.1 M(-1) cm(-1)) in this spectral region is due to
      the T1(n, pi*) <- S0 electronic transition. The 0(0)(0) origin band was assigned
      to the feature observed at 24,558.8 +/- 0.3 cm(-1). We have assigned 46 vibronic
      transitions in a region extending from -200 to +350 cm(-1) relative to the origin
      band. For the majority of these transitions, we have made corresponding
      assignments in the spectrum of the deuterated derivative 2CHO-2,6,6-d3. From the
      assignments, we determined fundamental frequencies for several vibrational modes
      in the T1(n, pi*) excited state of 2CHO, including the lowest ring-twisting (99.6
      cm(-1)) and ring-bending (262.2 cm(-1)) modes. These values compare to
      fundamentals of 122.2 cm(-1) and 251.9 cm(-1), respectively, determined
      previously for the isoconfigurational S1(n, pi*) excited state of 2CHO and 99 cm(
      1) and 248 cm(-1), respectively, for the S0 ground state. With the aid of quantum
      mechanical calculations, we have also ascertained descriptions for these two
      modes, thereby resolving ambiguities appearing in the previous literature. The
      ring-twisting mode (nu39) contains a significant contribution from O=C-C=C
      torsion, whereas the ring-bending mode (nu38 in the ground state) involves mainly
      the motion of C-5 with respect to the plane containing the other heavy atoms. The
      CRD spectroscopic data for the T1(n, pi*) state have allowed us to benchmark
      several computational methods for treating excited states, including time
      dependent density functional theory and an equation-of-motion coupled cluster
      method. In turn, the computational results provide an explanation for observed
      differences in the T1(n, pi*) vs. S1(n, pi*) ring frequencies.

PMID- 24320385
TI  - NMR T1 relaxation time measurements and calculations with translational and
      rotational components for liquid electrolytes containing LiBF4 and propylene
      carbonate.
AB  - Longitudinal relaxation (T1) measurements of (19)F, (7)Li, and (1)H in propylene
      carbonate/LiBF4 liquid electrolytes are reported. Comparison of T1 values with
      those for the transverse relaxation time (T2) confirm that the measurements are
      in the high temperature (low correlation time) limit of the T1 minimum. Using
      data from pulsed field gradient measurements of self-diffusion coefficients and
      measurements of solution viscosity measured elsewhere, it is concluded that
      although in general there are contributions to T1 from both translational and
      rotational motions. For the lithium ions, this is mainly translational, and for
      the fluorine ions mainly rotational. 

PMID- 24320386
TI  - The dynamical crossover in attractive colloidal systems.
AB  - We study the dynamical arrest in an adhesive hard-sphere colloidal system. We
      examine a micellar suspension of the Pluronic-L64 surfactant in the temperature
      (T) and volume fraction (phi) phase diagram. According to mode-coupling theory
      (MCT), this system is characterized by a cusp-like singularity and two glassy
      phases: an attractive glass (AG) phase and a repulsive glass (RG) phase. The T -
      phi phase diagram of this system as confirmed by a previous series of scattering
      data also exhibits a Percolation Threshold (PT) line, a reentrant behavior (AG
      liquid-RG), and a glass-to-glass transition. The AG phase can be generated out of
      the liquid phase by using T and phi as control parameters. We utilize viscosity
      and nuclear magnetic resonance (NMR) techniques. NMR data confirm all the
      characteristic properties of the colloidal system phase diagram and give evidence
      of the onset of a fractal-like percolating structure at a precise threshold. The
      MCT scaling laws used to study the shear viscosity as a function of phi and T
      show in both cases a fragile-to-strong liquid glass-forming dynamic crossover
      (FSC) located near the percolation threshold where the clustering process is
      fully developed. These results suggest a larger thermodynamic generality for this
      phenomenon, which is usually studied only as a function of the temperature. We
      also find that the critical values of the control parameters, coincident with the
      PT line, define the locus of the FSC. In the region between the FSC and the glass
      transition lines the system dynamics are dominated by clustering effects. We thus
      demonstrate that it is possible, using the conceptual framework provided by
      extended mode-coupling theory, to describe the way a system approaches dynamic
      arrest, taking into account both cage and hopping effects.

PMID- 24320387
TI  - Phase diagram of ammonium nitrate.
AB  - Ammonium Nitrate (AN) is a fertilizer, yet becomes an explosive upon a small
      addition of chemical impurities. The origin of enhanced chemical sensitivity in
      impure AN (or AN mixtures) is not well understood, posing significant safety
      issues in using AN even today. To remedy the situation, we have carried out an
      extensive study to investigate the phase stability of AN and its mixtures with
      hexane (ANFO-AN mixed with fuel oil) and Aluminum (Ammonal) at high pressures and
      temperatures, using diamond anvil cells (DAC) and micro-Raman spectroscopy. The
      results indicate that pure AN decomposes to N2, N2O, and H2O at the onset of the
      melt, whereas the mixtures, ANFO and Ammonal, decompose at substantially lower
      temperatures. The present results also confirm the recently proposed phase IV-IV'
      transition above 17 GPa and provide new constraints for the melting and phase
      diagram of AN to 40 GPa and 400 degrees C.

PMID- 24320388
TI  - The liquid surface of chiral ionic liquids as seen from molecular dynamics
      simulations combined with intrinsic analysis.
AB  - We present molecular-level insight into the liquid/gas interface of two chiral
      room-temperature ionic liquids (RTILs) derived from 1-n-butyl-3-methylimidazolium
      bromide ([bmim][Br]); namely, (R)-1-butyl-3-(3-hydroxy-2-methylpropyl)imidazolium
      bromide (hydroxypropyl) and 1-butyl-3-[(1R)-nopyl]imidazolium bromide (nopyl). We
      use our currently developed force field which was validated against the
      experimental bulk density, heat of vaporization, and surface tension of
      [bmim][Br]. The force field for the RTILs adopts the Chemistry at Harvard
      Molecular Mechanics (CHARMM) parameters for the intramolecular and repulsion
      dispersion interactions along with the reduced partial atomic charges based on ab
      initio calculations. The net charges of the ions are around +/-0.8e, which mimic
      the anion to cation charge transfer and many-body effects. Molecular dynamics
      simulations in the slab geometry combined with the intrinsic interface analysis
      are employed to provide a detailed description of the RTIL/gas interface in terms
      of the structural and dynamic properties of the interfacial, sub-interfacial, and
      central layers at a temperature of 300 K. The focus is on the comparison of the
      liquid/gas interface for the chiral RTILs with the interface for parent
      [bmim][Br]. The structure of the interface is elucidated by evaluating the
      surface roughness, intrinsic atomic density profiles, and orientation ordering of
      the cations. The dynamics of the ions at the interfacial region is characterized
      by computing the survival probability, and normal and lateral self-diffusion
      coefficients in the layers. 

PMID- 24320389
TI  - In situ self-assembled organic interface layers for the controlled growth of
      oligothiophene thin films on ferroelectric Pb(Zr(0.2)Ti(0.8))O3.
AB  - We introduce an in situ vacuum procedure for the optimal preparation and analysis
      of self-assembled monolayers (SAMs) as used in organic molecular electronics on
      ferroelectric lead zirconate titanate (PZT) substrates. Excellent ordering of
      oligothiophene semiconductor layers is heavily promoted through the presence of
      an interfacial bi-functional SAM layer that binds to both the oxidic PZT surface
      and the organic semiconductor molecules. The described method can be extended to
      other material combinations, featuring a variety of substrate materials and
      molecular functionalities. 

PMID- 24320390
TI  - Vapor condensation onto a non-volatile liquid drop.
AB  - Molecular dynamics simulations of miscible and partially miscible binary Lennard
      Jones mixtures are used to study the dynamics and thermodynamics of vapor
      condensation onto a non-volatile liquid drop in the canonical ensemble. When the
      system volume is large, the driving force for condensation is low and only a
      submonolayer of the solvent is adsorbed onto the liquid drop. A small degree of
      mixing of the solvent phase into the core of the particles occurs for the
      miscible system. At smaller volumes, complete film formation is observed and the
      dynamics of film growth are dominated by cluster-cluster coalescence. Mixing into
      the core of the droplet is also observed for partially miscible systems below an
      onset volume suggesting the presence of a solubility transition. We also develop
      a non-volatile liquid drop model, based on the capillarity approximations, that
      exhibits a solubility transition between small and large drops for partially
      miscible mixtures and has a hysteresis loop similar to the one observed in the
      deliquescence of small soluble salt particles. The properties of the model are
      compared to our simulation results and the model is used to study the formulation
      of classical nucleation theory for systems with low free energy barriers. 

PMID- 24320391
TI  - A fragment method for systematic improvement of anharmonic adsorbate vibrational
      frequencies: acetylene on Cu(001).
AB  - We suggest a novel method for systematic improvement of anharmonic adsorbate
      frequencies based on a fragment approach. The calculations are carried out by
      considering the adsorbed molecule separately and computing an energy correction
      using high-level ab initio method in addition to a standard calculation of the
      whole adsorbed system using quantum mechanical techniques with periodic boundary
      conditions. We demonstrate its reliability for a C2H2 molecule chemisorbed on a
      Cu(001) surface. We also show that the accuracy of the presented approach with a
      suitable description of the periodic surface depends mainly on the accuracy of
      the high-level ab initio method used to describe the adsorbate molecule.
      Moreover, our technique potentially allows to predict adsorbate vibrational
      spectra with spectroscopic accuracy. 

PMID- 24320392
TI  - Phase stabilities at a glance: stability diagrams of nickel dipnictides.
AB  - In the course of the recent advances in chemical structure prediction, a
      straightforward type of diagram to evaluate phase stabilities is presented based
      on an expedient example. Crystal structures and energetic stabilities of
      dipnictides NiPn2 (Pn = N, P, As, Sb, Bi) are systematically investigated by
      first principles calculations within the framework of density functional theory
      using the generalized gradient approximation to treat exchange and correlation.
      These dipnictides show remarkable polymorphism that is not yet understood
      systematically and offers room for the discovery of new phases. Relationships
      between the concerned structures including the marcasite, the pyrite, the
      arsenopyrite/CoSb2, and the NiAs2 types are highlighted by means of common
      structural fragments. Electronic stabilities of experimentally known and related
      AB2 structure types are presented graphically in so-called stability diagrams.
      Additionally, competing binary phases are taken into consideration in the
      diagrams to evaluate the stabilities of the title compounds with respect to
      decomposition. The main purpose of the stability diagrams is the introduction of
      an image that enables the estimation of phase stabilities at a single glance.
      Beyond that, some of the energetically favored structure types can be identified
      as potential new phases.

PMID- 24320393
TI  - Barrier height formation in organic blends/metal interfaces: case of
      tetrathiafulvalene-tetracyanoquinodimethane/Au(111).
AB  - The interface between the tetrathiafulvalene/tetracyanoquinodimethane (TTF-TCNQ)
      organic blend and the Au(111) metal surface is analyzed by Density Functional
      Theory calculations, including the effect of the charging energies on the
      molecule transport gaps. Given the strong donor and acceptor characters of the
      TTF and TCNQ molecules, respectively, there is a strong intermolecular
      interaction, with a relatively high charge transfer between the two organic
      materials, and between the organic layer and the metal surface. We find that the
      TCNQ LUMO peak is very close to the Fermi level; due to the interaction with the
      metal surface, the organic molecular levels are broadened, creating an important
      induced density of interface states (IDIS). We show that the interface energy
      level alignment is controlled by the charge transfer between TTF, TCNQ, and Au,
      and by the molecular dipoles created in the molecules because of their
      deformations when adsorbed on Au(111). A generalization of the Unified-IDIS
      model, to explain how the interface energy levels alignment is achieved for the
      case of this blended donor/acceptor organic layer, is presented by introducing
      matrix equations associated with the Charge Neutrality Levels of both organic
      materials and with their intermixed screening properties.

PMID- 24320394
TI  - Methane dissociative chemisorption and detailed balance on Pt(111): dynamical
      constraints and the modest influence of tunneling.
AB  - A dynamically biased (d-) precursor mediated microcanonical trapping (PMMT) model
      of the activated dissociative chemisorption of methane on Pt(111) is applied to a
      wide range of dissociative sticking experiments, and, by detailed balance, to the
      methane product state distributions from the thermal associative desorption of
      adsorbed hydrogen with coadsorbed methyl radicals. Tunneling pathways were
      incorporated into the d-PMMT model to better replicate the translational energy
      distribution of the desorbing methane product from the laser induced thermal
      reaction of coadsorbed hydrogen and methyl radicals occurring near T(s) = 395 K.
      Although tunneling is predicted to be inconsequential to the thermal dissociative
      chemisorption of CH4 on Pt(111) at the high temperatures of catalytic interest,
      once the temperature drops to 395 K the tunneling fraction of the reactive
      thermal flux reaches 15%, and as temperatures drop below 275 K the tunneling
      fraction exceeds 50%. The d-PMMT model parameters of {E0 = 58.9 kJ/mol, s = 2,
      eta(v) = 0.40} describe the apparent threshold energy for CH4/Pt(111)
      dissociative chemisorption, the number of surface oscillators involved in the
      precursor complex, and the efficacy of molecular vibrational energy to promote
      reaction, relative to translational energy directed along the surface normal.
      Molecular translations parallel to the surface and rotations are treated as
      spectator degrees of freedom. Transition state vibrational frequencies are
      derived from generalized gradient approximation-density functional theory
      electronic structure calculations. The d-PMMT model replicates the diverse range
      of experimental data available with good fidelity, including some new effusive
      molecular beam and ambient gas dissociative sticking measurements. Nevertheless,
      there are some indications that closer agreement between theory and experiments
      could be achieved if a surface efficacy less than one was introduced into the
      modeling as an additional dynamical constraint.

PMID- 24320395
TI  - Vibration responses of h-BN sheet to charge doping and external strain.
AB  - Based on density functional theory and density functional perturbation theory
      calculations, we systematically investigate the vibration responses of h-BN sheet
      to charge doping and external strains. It is found that under hole doping, the
      phonon frequencies of the ZO and TO branches at different wave vector q shift
      linearly with different slopes. Under electron doping, although the phonon
      frequencies shift irregularly, the shifting values are different at different
      phonon wave vectors. Interestingly, we find that external strain can restrain the
      irregular vibration responses of h-BN sheet to electron doping. The critical
      factor is revealed to be the relative position of the nearly free electron and
      boron p(z) states of h-BN sheet. Under external strains, the vibration responses
      of h-BN sheet are also found to be highly dependent on the phonon branches.
      Different vibration modes at different q points are revealed to be responsible
      for the vibration responses of h-BN sheet to charge doping and external strain.
      Our results point out a new way to detect the doping or strain status of h-BN
      sheet by measuring the vibration frequencies at different wave vector.

PMID- 24320396
TI  - Manipulating transport through a single-molecule junction.
AB  - Molecular Electronics deals with the realization of elementary electronic devices
      that rely on a single molecule. For electronic applications, the most important
      property of a single molecule is its conductance. Here we show how the
      conductance of a single octanethiol molecule can be measured and manipulated by
      varying the contact's interspace. This mechanical gating of the single molecule
      junction leads to a variation of the conductance that can be understood in terms
      of a tunable image charge effect. The image charge effect increases with a
      decrease of the contact's interspace due to a reduction of the effective
      potential barrier height of 1.5 meV/pm.

PMID- 24320397
TI  - Electronic excitations of bulk LiCl from many-body perturbation theory.
AB  - We present the quasiparticle band structure and the optical excitation spectrum
      of bulk LiCl, using many-body perturbation theory. Density-functional theory is
      used to calculate the ground-state geometry of the system. The quasiparticle band
      structure is calculated within the GW approximation. Taking the electron-hole
      interaction into consideration, electron-hole pair states and optical excitations
      are obtained by solving the Bethe-Salpeter equation for the electron-hole two
      particle Green function. The calculated band gap is 9.5 eV, which is in good
      agreement with the experimental result of 9.4 eV. And the calculated optical
      absorption spectrum, which contains an exciton peak at 8.8 eV and a resonant
      exciton peak at 9.8 eV, is also in good agreement with experimental data. 

PMID- 24320398
TI  - Microstructure and magnetic properties of magnetic fluids consisting of shifted
      dipole particles under the influence of an external magnetic field.
AB  - We investigate the structure of a recently proposed magnetic fluid consisting of
      shifted dipolar (SD) particles in an externally applied magnetic field via
      computer simulations. For standard dipolar fluids the applied magnetic field
      usually enhances the dipole-dipole correlations and facilitates chain formation
      whereas in the present system the effect of an external field can result in a
      break-up of clusters. We thoroughly investigate the origin of this phenomenon
      through analyzing first the ground states of the SD-particle systems as a
      function of an applied field. In a second step we quantify the microstructure of
      these systems as functions of the shift parameter, the effective interaction
      parameter, and the applied magnetic field strength. We conclude the paper by
      showing that with the proper choice of parameters, it is possible to create a
      system of SD-particles with highly interacting magnetic particles, whose initial
      susceptibility is below the Langevin susceptibility, and which remains spatially
      isotropic even in a very strong external magnetic field. 

PMID- 24320399
TI  - Binary mixed homopolymer brushes grafted on nanorod particles: a self-consistent
      field theory study.
AB  - We employ the self-consistent field theory to study phase structures of brush-rod
      systems composed of two chemically distinct linear homopolymers. The polymer
      chains are uniformly grafted on the surface of a nanorod particle of finite
      length and comparable radius to the polymer radius of gyration. A "masking"
      technique treating the cylindrical boundary is introduced to solve the modified
      diffusion equations with an efficient and high-order accurate pseudospectral
      method involving fast Fourier transform on an orthorhombic cell. A rich variety
      of structures for the phase separated brushes is predicted. Phase diagrams
      involving a series of system parameters, such as the aspect ratio of the nanorod,
      the grafting density, and the chain length are constructed. The results indicate
      that the phase structure of the mixed brush-rod system can be tailored by varying
      the grafted chain length and/or the aspect ratio of the rod to benefit the
      fabrication of polymeric nanocomposites.

PMID- 24320400
TI  - Conformation and elasticity of a charged polymer chain bridging two
      nanoparticles.
AB  - A complex composed of a charged flexible polymer chain irreversibly attached with
      its ends to surfaces of two nanoparticles was investigated using the Metropolis
      Monte Carlo method on a simple cubic lattice. The simulations were performed in
      the presence of explicit ions. The bridging chain and the nanoparticles bearing
      the same and the opposite sign charges were considered. Changes in the free
      energy of the complex upon its stretching or compression, together with the
      magnitude of the elastic force, were examined. The relative roles of energetic
      and entropic effects in determining the properties of the complex were
      identified. Also, the adsorption of charged monomers on the opposite-sign charged
      nanoparticles and its influence on the examined quantities was studied. Moreover,
      a simple semi-analytical approach to the thermodynamics of the polymer bridge was
      derived. 

PMID- 24320401
TI  - Crystallization mechanism in melts of short n-alkane chains.
AB  - We study crystallization in a model system for eicosane (C20) by means of
      molecular dynamics simulation and identify the microscopic mechanisms of
      homogeneous crystal nucleation and growth. For the nucleation process, we observe
      that chains first align and then straighten. Then the local density increases and
      finally the monomer units become ordered positionally. The subsequent crystal
      growth process is characterized by a sliding-in motion of the chains. Chains
      preferably attach to the crystalline cluster with one end and then move along the
      stems of already crystallized chains towards their final position. This process
      is cooperative, i.e., neighboring chains tend to get attached in clusters rather
      than independently. 

PMID- 24320402
TI  - Fluctuation effects on the order-disorder transition in polydisperse copolymer
      melts.
AB  - Using single chain in mean field simulation approach, we examine the influence of
      fluctuation effects on the order-disorder transition (ODT) of polydisperse
      copolymer systems. We consider two model systems: (i) molecular weight
      polydisperse systems represented by AB diblock copolymer melts having
      monodisperse A blocks and polydisperse B blocks; and (ii) compositionally
      polydisperse symmetric diblock copolymer systems. In each case, we present
      results for the fluctuation-induced shift in the ODT from the corresponding mean
      field predictions. In both models, an increase in polydispersity enhances the
      influence of fluctuations. Moreover, for compositionally polydisperse systems, we
      observe that the effects of fluctuations show similar trends in systems
      containing quenched and annealed representation of sequences. 

PMID- 24320403
TI  - Spatio-temporal hierarchy in the dynamics of a minimalist protein model.
AB  - A method for time series analysis of molecular dynamics simulation of a protein
      is presented. In this approach, wavelet analysis and principal component analysis
      are combined to decompose the spatio-temporal protein dynamics into contributions
      from a hierarchy of different time and space scales. Unlike the conventional
      Fourier-based approaches, the time-localized wavelet basis captures the
      vibrational energy transfers among the collective motions of proteins. As an
      illustrative vehicle, we have applied our method to a coarse-grained minimalist
      protein model. During the folding and unfolding transitions of the protein,
      vibrational energy transfers between the fast and slow time scales were observed
      among the large-amplitude collective coordinates while the other small-amplitude
      motions are regarded as thermal noise. Analysis employing a Gaussian-based
      measure revealed that the time scales of the energy redistribution in the
      subspace spanned by such large-amplitude collective coordinates are slow compared
      to the other small-amplitude coordinates. Future prospects of the method are
      discussed in detail. 

PMID- 24320404
TI  - Slow dynamics of a protein backbone in molecular dynamics simulation revealed by
      time-structure based independent component analysis.
AB  - We recently proposed the method of time-structure based independent component
      analysis (tICA) to examine the slow dynamics involved in conformational
      fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y.
      Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study
      focused on domain motions of the protein and examined its dynamics by using rigid
      body domain analysis and tICA. However, the protein changes its conformation not
      only through domain motions but also by various types of motions involving its
      backbone and side chains. Some of these motions might occur on a slow time scale:
      we hypothesize that if so, we could effectively detect and characterize them
      using tICA. In the present study, we investigated slow dynamics of the protein
      backbone using MD simulation and tICA. The selected target protein was lysine-,
      arginine-, ornithine-binding protein (LAO), which comprises two domains and
      undergoes large domain motions. MD simulation of LAO in explicit water was
      performed for 1 MUs, and the obtained trajectory of C(alpha) atoms in the
      backbone was analyzed by tICA. This analysis successfully provided us with slow
      modes for LAO that represented either domain motions or local movements of the
      backbone. Further analysis elucidated the atomic details of the suggested local
      motions and confirmed that these motions truly occurred on the expected slow time
      scale.

PMID- 24320405
TI  - Comment on "Molecular dynamics simulation study of nonconcatenated ring polymers
      in a melt. I. Statics" [J. Chem. Phys. 134, 204904 (2011)].

PMID- 24320406
TI  - Response to "Comment on 'Molecular dynamics simulation study of nonconcatenated
      ring polymers in a melt. I. Statics"' [J. Chem. Phys. 139, 217101 (2013)].

PMID- 24320407
TI  - Point/Counterpoint. The future h-index is an excellent way to predict scientists'
      future impact.

PMID- 24320408
TI  - A super-resolution ultrasound method for brain vascular mapping.
AB  - PURPOSE: High-resolution vascular imaging has not been achieved in the brain due
      to limitations of current clinical imaging modalities. The authors present a
      method for transcranial ultrasound imaging of single micrometer-size bubbles
      within a tube phantom. METHODS: Emissions from single bubbles within a tube
      phantom were mapped through an ex vivo human skull using a sparse hemispherical
      receiver array and a passive beamforming algorithm. Noninvasive phase and
      amplitude correction techniques were applied to compensate for the aberrating
      effects of the skull bone. The positions of the individual bubbles were estimated
      beyond the diffraction limit of ultrasound to produce a super-resolution image of
      the tube phantom, which was compared with microcomputed tomography (micro-CT).
      RESULTS: The resulting super-resolution ultrasound image is comparable to results
      obtained via the micro-CT for small tissue specimen imaging. CONCLUSIONS: This
      method provides superior resolution to deep-tissue contrast ultrasound and has
      the potential to be extended to provide complete vascular network imaging in the
      brain.

PMID- 24320409
TI  - Quantification of organ motion based on an adaptive image-based scale invariant
      feature method.
AB  - PURPOSE: The availability of corresponding landmarks in IGRT image series allows
      quantifying the inter and intrafractional motion of internal organs. In this
      study, an approach for the automatic localization of anatomical landmarks is
      presented, with the aim of describing the nonrigid motion of anatomo-pathological
      structures in radiotherapy treatments according to local image contrast. METHODS:
      An adaptive scale invariant feature transform (SIFT) was developed from the
      integration of a standard 3D SIFT approach with a local image-based contrast
      definition. The robustness and invariance of the proposed method to shape
      preserving and deformable transforms were analyzed in a CT phantom study. The
      application of contrast transforms to the phantom images was also tested, in
      order to verify the variation of the local adaptive measure in relation to the
      modification of image contrast. The method was also applied to a lung 4D CT
      dataset, relying on manual feature identification by an expert user as ground
      truth. The 3D residual distance between matches obtained in adaptive-SIFT was
      then computed to verify the internal motion quantification with respect to the
      expert user. Extracted corresponding features in the lungs were used as
      regularization landmarks in a multistage deformable image registration (DIR)
      mapping the inhale vs exhale phase. The residual distances between the warped
      manual landmarks and their reference position in the inhale phase were evaluated,
      in order to provide a quantitative indication of the registration performed with
      the three different point sets. RESULTS: The phantom study confirmed the method
      invariance and robustness properties to shape-preserving and deformable
      transforms, showing residual matching errors below the voxel dimension. The
      adapted SIFT algorithm on the 4D CT dataset provided automated and accurate
      motion detection of peak to peak breathing motion. The proposed method resulted
      in reduced residual errors with respect to standard SIFT, providing a motion
      description comparable to expert manual identification, as confirmed by DIR.
      CONCLUSIONS: The application of the method to a 4D lung CT patient dataset
      demonstrated adaptive-SIFT potential as an automatic tool to detect landmarks for
      DIR regularization and internal motion quantification. Future works should
      include the optimization of the computational cost and the application of the
      method to other anatomical sites and image modalities.

PMID- 24320410
TI  - The feasibility study and characterization of a two-dimensional diode array in
      "magic phantom" for high dose rate brachytherapy quality assurance.
AB  - PURPOSE: High dose rate (HDR) brachytherapy is a radiation treatment technique
      capable of delivering large dose rates to the tumor. Radiation is delivered using
      remote afterloaders to drive highly active sources (commonly (192)Ir with an air
      KERMA strength range between 20,000 and 40,000 U, where 1 U = 1 MUGy m(2)/h in
      air) through applicators directly into the patient's prescribed region of
      treatment. Due to the obvious ramifications of incorrect treatment while using
      such an active source, it is essential that there are methods for quality
      assurance (QA) that can directly and accurately verify the treatment plan and the
      functionality of the remote afterloader. This paper describes the feasibility
      study of a QA system for HDR brachytherapy using a phantom based two-dimensional
      11 * 11 epitaxial diode array, named "magic phantom." METHODS: The HDR
      brachytherapy treatment plan is translated to the phantom with two rows of 10 (20
      in total) HDR source flexible catheters, arranged above and below the diode array
      "magic plate" (MP). Four-dimensional source tracking in each catheter is based
      upon a developed fast iterative algorithm, utilizing the response of the diodes
      in close proximity to the (192)Ir source, sampled at 100 ms intervals by a fast
      data acquisition (DAQ) system. Using a (192)Ir source in a solid water phantom,
      the angular response of the developed epitaxial diodes utilized in the MP and
      also the variation of the MP response as a function of the source-to-detector
      distance (SDD) were investigated. These response data are then used by an
      iterative algorithm for source dwelling position determination. A measurement of
      the average transit speed between dwell positions was performed using the diodes
      and a fast DAQ. RESULTS: The angular response of the epitaxial diode showed a
      variation of 15% within 360 degrees , with two flat regions above and below the
      detector face with less than 5% variation. For SDD distances of between 5 and 30
      mm the relative response of the epitaxial diodes used in the MP is in good
      agreement (within 8%) with radial dose function measurements found within the TG
      43 protocol, with SDD of up to 70 mm showing a 40% over response. A method for
      four-dimensional localization of the HDR source was developed, allowing the
      source dwell position to be derived within 0.50 mm of the expected position. An
      estimation of the average transit speed for varying step sizes was determined and
      was found to increase from (12.8 +/- 0.3) up to (38.6 +/- 0.4) cm/s for a step
      size of 2.5 and 50 mm, respectively. CONCLUSIONS: Our characterization of the
      designed QA "magic phantom" with MP in realistic HDR photon fields demonstrates
      the promising performance for real-time source position tracking in four
      dimensions and measurements of transit times. Further development of this system
      will allow a full suite for QA in HDR brachytherapy and analysis, and for future
      in vivo tracking.

PMID- 24320411
TI  - A virtual phantom library for the quantification of deformable image registration
      uncertainties in patients with cancers of the head and neck.
AB  - PURPOSE: Deformable image registration (DIR) is being used increasingly in
      various clinical applications. However, the underlying uncertainties of DIR are
      not well-understood and a comprehensive methodology has not been developed for
      assessing a range of interfraction anatomic changes during head and neck cancer
      radiotherapy. This study describes the development of a library of clinically
      relevant virtual phantoms for the purpose of aiding clinicians in the QA of DIR
      software. These phantoms will also be available to the community for the
      independent study and comparison of other DIR algorithms and processes. METHODS:
      Each phantom was derived from a pair of kVCT volumetric image sets. The first
      images were acquired of head and neck cancer patients prior to the start-of
      treatment and the second were acquired near the end-of-treatment. A research
      algorithm was used to autosegment and deform the start-of-treatment (SOT) images
      according to a biomechanical model. This algorithm allowed the user to adjust the
      head position, mandible position, and weight loss in the neck region of the SOT
      images to resemble the end-of-treatment (EOT) images. A human-guided thin-plate
      splines algorithm was then used to iteratively apply further deformations to the
      images with the objective of matching the EOT anatomy as closely as possible. The
      deformations from each algorithm were combined into a single deformation vector
      field (DVF) and a simulated end-of-treatment (SEOT) image dataset was generated
      from that DVF. Artificial noise was added to the SEOT images and these images,
      along with the original SOT images, created a virtual phantom where the
      underlying "ground-truth" DVF is known. Images from ten patients were deformed in
      this fashion to create ten clinically relevant virtual phantoms. The virtual
      phantoms were evaluated to identify unrealistic DVFs using the normalized cross
      correlation (NCC) and the determinant of the Jacobian matrix. A commercial
      deformation algorithm was applied to the virtual phantoms to show how they may be
      used to generate estimates of DIR uncertainty. RESULTS: The NCC showed that the
      simulated phantom images had greater similarity to the actual EOT images than the
      images from which they were derived, supporting the clinical relevance of the
      synthetic deformation maps. Calculation of the Jacobian of the "ground-truth"
      DVFs resulted in only positive values. As an example, mean error statistics are
      presented for all phantoms for the brainstem, cord, mandible, left parotid, and
      right parotid. CONCLUSIONS: It is essential that DIR algorithms be evaluated
      using a range of possible clinical scenarios for each treatment site. This work
      introduces a library of virtual phantoms intended to resemble real cases for
      interfraction head and neck DIR that may be used to estimate and compare the
      uncertainty of any DIR algorithm.

PMID- 24320412
TI  - Fan-beam intensity modulated proton therapy.
AB  - PURPOSE: This paper presents a concept for a proton therapy system capable of
      delivering intensity modulated proton therapy using a fan beam of protons. This
      system would allow present and future gantry-based facilities to deliver state-of
      the-art proton therapy with the greater normal tissue sparing made possible by
      intensity modulation techniques. METHODS: A method for producing a divergent fan
      beam of protons using a pair of electromagnetic quadrupoles is described and
      particle transport through the quadrupole doublet is simulated using a
      commercially available software package. To manipulate the fan beam of protons, a
      modulation device is developed. This modulator inserts or retracts acrylic leaves
      of varying thickness from subsections of the fan beam. Each subsection, or beam
      channel, creates what effectively becomes a beam spot within the fan area. Each
      channel is able to provide 0-255 mm of range shift for its associated beam spot,
      or stop the beam and act as an intensity modulator. Results of particle transport
      simulations through the quadrupole system are incorporated into the MCNPX Monte
      Carlo transport code along with a model of the range and intensity modulation
      device. Several design parameters were investigated and optimized, culminating in
      the ability to create topotherapy treatment plans using distal-edge tracking on
      both phantom and patient datasets. RESULTS: Beam transport calculations show that
      a pair of electromagnetic quadrupoles can be used to create a divergent fan beam
      of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and
      48 cm, respectively, with transverse field gradients less than 20 T/m, which is
      within the range of water-cooled magnets for the quadrupole radii used. MCNPX
      simulations of topotherapy treatment plans suggest that, when using the distal
      edge tracking delivery method, many delivery angles are more important than
      insisting on narrow beam channel widths in order to obtain conformal target
      coverage. Overall, the sharp distal falloff of a proton depth-dose distribution
      was found to provide sufficient control over the dose distribution to meet
      objectives, even with coarse lateral resolution and channel widths as large as 2
      cm. Treatment plans on both phantom and patient data show that dose conformity
      suffers when treatments are delivered from less than approximately ten angles.
      Treatment time for a sample prostate delivery is estimated to be on the order of
      10 min, and neutron production is estimated to be comparable to that found for
      existing collimated systems. CONCLUSIONS: Fan beam proton therapy is a method of
      delivering intensity modulated proton therapy which may be employed as an
      alternative to magnetic scanning systems. A fan beam of protons can be created by
      a set of quadrupole magnets and modified by a dual-purpose range and intensity
      modulator. This can be used to deliver inversely planned treatments, with spot
      intensities optimized to meet user defined dose objectives. Additionally, the
      ability of a fan beam delivery system to effectively treat multiple beam spots
      simultaneously may provide advantages as compared to spot scanning deliveries.

PMID- 24320413
TI  - Extension of PENELOPE to protons: simulation of nuclear reactions and benchmark
      with Geant4.
AB  - PURPOSE: Describing the implementation of nuclear reactions in the extension of
      the Monte Carlo code (MC) PENELOPE to protons (PENH) and benchmarking with
      Geant4. METHODS: PENH is based on mixed-simulation mechanics for both elastic and
      inelastic electromagnetic collisions (EM). The adopted differential cross
      sections for EM elastic collisions are calculated using the eikonal approximation
      with the Dirac-Hartree-Fock-Slater atomic potential. Cross sections for EM
      inelastic collisions are computed within the relativistic Born approximation,
      using the Sternheimer-Liljequist model of the generalized oscillator strength.
      Nuclear elastic and inelastic collisions were simulated using explicitly the
      scattering analysis interactive dialin database for (1)H and ICRU 63 data for
      (12)C, (14)N, (16)O, (31)P, and (40)Ca. Secondary protons, alphas, and deuterons
      were all simulated as protons, with the energy adapted to ensure consistent
      range. Prompt gamma emission can also be simulated upon user request. Simulations
      were performed in a water phantom with nuclear interactions switched off or on
      and integral depth-dose distributions were compared. Binary-cascade and
      precompound models were used for Geant4. Initial energies of 100 and 250 MeV were
      considered. For cases with no nuclear interactions simulated, additional
      simulations in a water phantom with tight resolution (1 mm in all directions)
      were performed with FLUKA. Finally, integral depth-dose distributions for a 250
      MeV energy were computed with Geant4 and PENH in a homogeneous phantom with,
      first, ICRU striated muscle and, second, ICRU compact bone. RESULTS: For
      simulations with EM collisions only, integral depth-dose distributions were
      within 1%/1 mm for doses higher than 10% of the Bragg-peak dose. For central-axis
      depth-dose and lateral profiles in a phantom with tight resolution, there are
      significant deviations between Geant4 and PENH (up to 60%/1 cm for depth-dose
      distributions). The agreement is much better with FLUKA, with deviations within
      3%/3 mm. When nuclear interactions were turned on, agreement (within 6% before
      the Bragg-peak) between PENH and Geant4 was consistent with uncertainties on
      nuclear models and cross sections, whatever the material simulated (water,
      muscle, or bone). CONCLUSIONS: A detailed and flexible description of nuclear
      reactions has been implemented in the PENH extension of PENELOPE to protons,
      which utilizes a mixed-simulation scheme for both elastic and inelastic EM
      collisions, analogous to the well-established algorithm for electrons/positrons.
      PENH is compatible with all current main programs that use PENELOPE as the MC
      engine. The nuclear model of PENH is realistic enough to give dose distributions
      in fair agreement with those computed by Geant4.

PMID- 24320414
TI  - Source position verification and dosimetry in HDR brachytherapy using an EPID.
AB  - PURPOSE: Accurate treatment delivery in high dose rate (HDR) brachytherapy
      requires correct source dwell positions and dwell times to be administered
      relative to each other and to the surrounding anatomy. Treatment delivery
      inaccuracies predominantly occur for two reasons: (i) anatomical movement or (ii)
      as a result of human errors that are usually related to incorrect implementation
      of the planned treatment. Electronic portal imaging devices (EPIDs) were
      originally developed for patient position verification in external beam
      radiotherapy and their application has been extended to provide dosimetric
      information. The authors have characterized the response of an EPID for use with
      an (192)Ir brachytherapy source to demonstrate its use as a verification device,
      providing both source position and dosimetric information. METHODS:
      Characterization of the EPID response using an (192)Ir brachytherapy source
      included investigations of reproducibility, linearity with dose rate, photon
      energy dependence, and charge build-up effects associated with exposure time and
      image acquisition time. Source position resolution in three dimensions was
      determined. To illustrate treatment verification, a simple treatment plan was
      delivered to a phantom and the measured EPID dose distribution compared with the
      planned dose. RESULTS: The mean absolute source position error in the plane
      parallel to the EPID, for dwells measured at 50, 100, and 150 mm source to
      detector distances (SDD), was determined to be 0.26 mm. The resolution of the z
      coordinate (perpendicular distance from detector plane) is SDD dependent with 95%
      confidence intervals of +/- 0.1, +/- 0.5, and +/- 2.0 mm at SDDs of 50, 100, and
      150 mm, respectively. The response of the EPID is highly linear to dose rate. The
      EPID exhibits an over-response to low energy incident photons and this
      nonlinearity is incorporated into the dose calibration procedure. A distance
      (spectral) dependent dose rate calibration procedure has been developed. The
      difference between measured and planned dose is less than 2% for 98.0% of pixels
      in a two-dimensional plane at an SDD of 100 mm. CONCLUSIONS: Our application of
      EPID dosimetry to HDR brachytherapy provides a quality assurance measure of the
      geometrical distribution of the delivered dose as well as the source positions,
      which is not possible with any current HDR brachytherapy verification system.

PMID- 24320415
TI  - The use of computed radiography plates to determine light and radiation field
      coincidence.
AB  - PURPOSE: Photo-stimulable phosphor computed radiography (CR) has characteristics
      that allow the output to be manipulated by both radiation and optical light. The
      authors have developed a method that uses these characteristics to carry out
      radiation field and light field coincidence quality assurance on linear
      accelerators. METHODS: CR detectors from Kodak were used outside their cassettes
      to measure both radiation and light field edges from a Varian linear accelerator.
      The CR detector was first exposed to a radiation field and then to a slightly
      smaller light field. The light impinged on the detector's latent image, removing
      to an extent the portion exposed to the light field. The detector was then
      digitally scanned. A MATLAB-based algorithm was developed to automatically
      analyze the images and determine the edges of the light and radiation fields, the
      vector between the field centers, and the crosshair center. Radiographic film was
      also used as a control to confirm the radiation field size. RESULTS: Analysis
      showed a high degree of repeatability with the proposed method. Results between
      the proposed method and radiographic film showed excellent agreement of the
      radiation field. The effect of varying monitor units and light exposure time was
      tested and found to be very small. Radiation and light field sizes were
      determined with an uncertainty of less than 1 mm, and light and crosshair centers
      were determined within 0.1 mm. CONCLUSIONS: A new method was developed to
      digitally determine the radiation and light field size using CR photo-stimulable
      phosphor plates. The method is quick and reproducible, allowing for the
      streamlined and robust assessment of light and radiation field coincidence, with
      no observer interpretation needed.

PMID- 24320416
TI  - Correcting radiation survey data to account for increased leakage during
      intensity modulated radiotherapy treatments.
AB  - PURPOSE: Intensity modulated radiotherapy (IMRT) treatments require more beam-on
      time and produce more linac head leakage to deliver similar doses to
      conventional, unmodulated, radiotherapy treatments. It is necessary to take this
      increased leakage into account when evaluating the results of radiation surveys
      around bunkers that are, or will be, used for IMRT. The recommended procedure of
      applying a monitor-unit based workload correction factor to secondary barrier
      survey measurements, to account for this increased leakage when evaluating
      radiation survey measurements around IMRT bunkers, can lead to potentially costly
      overestimation of the required barrier thickness. This study aims to provide
      initial guidance on the validity of reducing the value of the correction factor
      when applied to different radiation barriers (primary barriers, doors, maze
      walls, and other walls) by evaluating three different bunker designs. METHODS:
      Radiation survey measurements of primary, scattered, and leakage radiation were
      obtained at each of five survey points around each of three different
      radiotherapy bunkers and the contribution of leakage to the total measured
      radiation dose at each point was evaluated. Measurements at each survey point
      were made with the linac gantry set to 12 equidistant positions from 0 degrees 
      to 330 degrees , to assess the effects of radiation beam direction on the
      results. RESULTS: For all three bunker designs, less than 0.5% of dose measured
      at and alongside the primary barriers, less than 25% of the dose measured outside
      the bunker doors and up to 100% of the dose measured outside other secondary
      barriers was found to be caused by linac head leakage. CONCLUSIONS: Results of
      this study suggest that IMRT workload corrections are unnecessary, for survey
      measurements made at and alongside primary barriers. Use of reduced IMRT workload
      correction factors is recommended when evaluating survey measurements around a
      bunker door, provided that a subset of the measurements used in this study are
      repeated for the bunker in question. Reduction of the correction factor for other
      secondary barrier survey measurements is not recommended unless the contribution
      from leakage is separately evaluated.

PMID- 24320417
TI  - Evaluation of the cone beam CT for internal target volume localization in lung
      stereotactic radiotherapy in comparison with 4D MIP images.
AB  - PURPOSE: To investigate whether the three-dimensional cone-beam CT (CBCT) is
      clinically equivalent to the four-dimensional computed tomography (4DCT) maximum
      intensity projection (MIP) reconstructed images for internal target volume (ITV)
      localization in image-guided lung stereotactic radiotherapy. METHODS: A ball
      shaped polystyrene phantom with built-in cube, sphere, and cone of known volumes
      was attached to a motor-driven platform, which simulates a sinusoidal movement
      with changeable motion amplitude and frequency. Target motion was simulated in
      the patient in a superior-inferior (S-I) direction with three motion periods and
      2 cm peak-to-peak amplitudes. The Varian onboard Exact-Arms kV CBCT system and
      the GE LightSpeed four-slice CT integrated with the respiratory-position
      management 4DCT scanner were used to scan the moving phantom. MIP images were
      generated from the 4DCT images. The clinical equivalence of the two sets of
      images was evaluated by comparing the extreme locations of the moving objects
      along the motion direction, the centroid position of the ITV, and the ITV volumes
      that were contoured automatically by Velocity or calculated with an imaging
      gradient method. The authors compared the ITV volumes determined by the above
      methods with those theoretically predicted by taking into account the physical
      object dimensions and the motion amplitudes. The extreme locations were
      determined by the gradient method along the S-I axis through the center of the
      object. The centroid positions were determined by autocenter functions. The
      effect of motion period on the volume sizes was also studied. RESULTS: It was
      found that the extreme locations of the objects determined from the two image
      modalities agreed with each other satisfactorily. They were not affected by the
      motion period. The average difference between the two modalities in the extreme
      locations was 0.68% for the cube, 1.35% for the sphere, and 0.5% for the cone,
      respectively. The maximum difference in the centroid position of the cylinder,
      sphere, and cone was less than 1.4 mm between the two modalities for all motion
      periods studied. For the ITV volume evaluation, the authors found that both MIP
      based and CBCT-based ITVs increased with increases of motion period. Furthermore,
      the MIP-based ITV volumes were generally larger than those determined from the
      CBCT images, with the difference in autocontoured volumes being 2.57%, 1.66%, and
      1.82% for the sphere, cylinder, and cone, respectively, while these differences
      increased to 9.57%, 3.52%, 8.71% for the above objects when the gradient method
      was used. The authors found that the autocontour method was accurate enough to
      predict the actual ITV values with the absolute differences less than 2.4%
      comparing to the theoretically predicted values. CONCLUSIONS: The extreme
      location and the centroid position of the objects agree with each other between
      the two image modalities when the breathing motion is sinusoidal. Although the
      ITV volumes delineated from both image modalities changed with the motion period,
      the differences in ITV between the two modalities were minimal when an optimized
      window level was used. The authors' results suggest that CBCT and MIP images are
      equivalent in determining an ITV's position in the conditions studied. The CBCT
      is adequate in providing imaging-guidance for lung cancer treatment.

PMID- 24320418
TI  - Evaluation of a new six degrees of freedom couch for radiation therapy.
AB  - PURPOSE: The aim of this work is to evaluate the geometric accuracy of a
      prerelease version of a new six degrees of freedom (6DoF) couch. Additionally, a
      quality assurance method for 6DoF couches is proposed. METHODS: The main
      principle of the performance tests was to request a known shift for the 6DoF
      couch and to compare this requested shift with the actually applied shift by
      independently measuring the applied shift using different methods (graph paper,
      laser, inclinometer, and imaging system). The performance of each of the six axes
      was tested separately as well as in combination with the other axes. Functional
      cases as well as realistic clinical cases were analyzed. The tests were performed
      without a couch load and with a couch load of up to 200 kg and shifts in the
      range between -4 and +4 cm for the translational axes and between -3 degrees  and
      +3 degrees  for the rotational axes were applied. The quality assurance method of
      the new 6DoF couch was performed using a simple cube phantom and the imaging
      system. RESULTS: The deviations (mean +/- one standard deviation) accumulated
      over all performance tests between the requested shifts and the measurements of
      the applied shifts were -0.01 +/- 0.02, 0.01 +/- 0.02, and 0.01 +/- 0.02 cm for
      the longitudinal, lateral, and vertical axes, respectively. The corresponding
      values for the three rotational axes couch rotation, pitch, and roll were 0.03
      degrees  +/- 0.06 degrees , -0.04 degrees  +/- 0.12 degrees , and -0.01 degrees 
      +/- 0.08 degrees , respectively. There was no difference found between the tests
      with and without a couch load of up to 200 kg. CONCLUSIONS: The new 6DoF couch is
      able to apply requested shifts with high accuracy. It has the potential to be
      used for treatment techniques with the highest demands in patient setup accuracy
      such as those needed in stereotactic treatments. Shifts can be applied
      efficiently and automatically. Daily quality assurance of the 6DoF couch can be
      performed in an easy and efficient way. Long-term stability has to be evaluated
      in further tests.

PMID- 24320419
TI  - Strategies for automatic online treatment plan reoptimization using clinical
      treatment planning system: a planning parameters study.
AB  - PURPOSE: Adaptive radiation therapy for prostate cancer using online
      reoptimization provides an improved control of interfractional anatomy
      variations. However, the clinical implementation of online reoptimization is
      currently limited by the low efficiency of current strategies and the
      difficulties associated with integration into the current treatment planning
      system. This study investigates the strategies for performing fast (~2 min)
      automatic online reoptimization with a clinical fluence-map-based treatment
      planning system; and explores the performance with different input parameters
      settings: dose-volume histogram (DVH) objective settings, starting stage, and
      iteration number (in the context of real time planning). METHODS: Simulated
      treatments of 10 patients were reoptimized daily for the first week of treatment
      (5 fractions) using 12 different combinations of optimization strategies. Options
      for objective settings included guideline-based RTOG objectives, patient-specific
      objectives based on anatomy on the planning CT, and daily-CBCT anatomy-based
      objectives adapted from planning CT objectives. Options for starting stages
      involved starting reoptimization with and without the original plan's fluence
      map. Options for iteration numbers were 50 and 100. The adapted plans were then
      analyzed by statistical modeling, and compared both in terms of dosimetry and
      delivery efficiency. RESULTS: All online reoptimized plans were finished within
      ~2 min with excellent coverage and conformity to the daily target. The three
      input parameters, i.e., DVH objectives, starting stage, and iteration number,
      contributed to the outcome of optimization nearly independently. Patient-specific
      objectives generally provided better OAR sparing compared to guideline-based
      objectives. The benefit in high-dose sparing from incorporating daily anatomy
      into objective settings was positively correlated with the relative change in OAR
      volumes from planning CT to daily CBCT. The use of the original plan fluence map
      as the starting stage reduced OAR dose at the mid-dose region, but increased the
      monitor units by 17%. Differences of only 2cc or less in OAR V50%/V70Gy/V76Gy
      were observed between 100 and 50 iterations. CONCLUSIONS: It is feasible to
      perform automatic online reoptimization in ~2 min using a clinical treatment
      planning system. Selecting optimal sets of input parameters is the key to
      achieving high quality reoptimized plans, and should be based on the individual
      patient's daily anatomy, delivery efficiency, and time allowed for plan
      adaptation.

PMID- 24320420
TI  - Spatial and temporal performance of 3D optical surface imaging for real-time head
      position tracking.
AB  - PURPOSE: The spatial and temporal tracking performance of a commercially
      available 3D optical surface imaging system is evaluated for its potential use in
      frameless stereotactic radiosurgery head tracking applications. METHODS: Both 3D
      surface and infrared (IR) marker tracking were performed simultaneously on a head
      phantom mounted on an xyz motion stage and on four human subjects. To allow
      spatial and temporal comparison on human subjects, three points were
      simultaneously monitored, including the upper facial region (3D surface), a
      dental plate (IR markers), and upper forehead (IR markers). RESULTS: For both
      static and dynamic phantom studies, the 3D surface tracker was found to have a
      root mean squared error (RMSE) of approximately 0.30 mm for region-of-interest
      (ROI) surface sizes greater than 1000 vertex points. Although, the processing
      period (1/fps) of the 3D surface system was found to linearly increase as a
      function of the number of ROI vertex points, the tracking accuracy was found to
      be independent of ROI size provided that the ROI was sufficiently large and
      contained features for registration. For human subjects, the RMSE between 3D
      surface tracking and IR marker tracking modalities was 0.22 mm left-right (x
      axis), 0.44 mm superior-inferior (y-axis), 0.27 mm anterior-posterior (z-axis),
      0.29 degrees  pitch (around x-axis), 0.18 degrees  roll (around y-axis), and 0.15
      degrees  yaw (around z-axis). CONCLUSIONS: 3D surface imaging has the potential
      to provide submillimeter level head motion tracking. This is provided that a
      highly accurate camera-to-LINAC frame of reference calibration can be performed
      and that the reference ROI is of sufficient size and contains suitable surface
      features for registration.

PMID- 24320421
TI  - Interplay effects between dose distribution quality and positioning accuracy in
      total marrow irradiation with volumetric modulated arc therapy.
AB  - PURPOSE: To evaluate the dosimetric consequences of inaccurate isocenter
      positioning during treatment of total marrow (lymph-node) irradiation (TMI-TMLI)
      using volumetric modulated arc therapy (VMAT). METHODS: Four patients treated
      with TMI and TMLI were randomly selected from the internal database. Plans were
      optimized with VMAT technique. Planning target volume (PTV) included all the body
      bones; for TMLI, lymph nodes and spleen were considered into the target, too.
      Dose prescription to PTV was 12 Gy in six fractions, two times per day for TMI,
      and 2 Gy in single fraction for TMLI. Ten arcs on five isocenters (two arcs for
      isocenter) were used to cover the upper part of PTV (i.e., from cranium to middle
      femurs). For each plan, three series of random shifts with values between -3 and
      +3 mm and three between -5 and +5 mm were applied to the five isocenters
      simulating involuntary patient motion during treatment. The shifts were applied
      separately in the three directions: left-right (L-R), anterior-posterior (A-P),
      and cranial-caudal (C-C). The worst case scenario with simultaneous random shifts
      in all directions simultaneously was considered too. Doses were recalculated for
      the 96 shifted plans (24 for each patient). RESULTS: For all shifts, differences
      <0.5% were found for mean doses to PTV, body, and organs at risk with volumes
      >100 cm(3). Maximum doses increased up to 15% for C-C shifted plans. PTV covered
      by the 95% isodose decreased of 2%-8% revealing target underdosage with the
      highest values in C-C direction. CONCLUSIONS: The correct isocenter repositioning
      of TMI-TMLI patients is fundamental, in particular in C-C direction, in order to
      avoid over- and underdosages especially in the overlap regions. For this reason,
      a dedicated immobilization system was developed in the authors' center to best
      immobilize the patient.

PMID- 24320422
TI  - A new concept of pencil beam dose calculation for 40-200 keV photons using
      analytical dose kernels.
AB  - PURPOSE: The advent of widespread kV-cone beam computer tomography in image
      guided radiation therapy and special therapeutic application of keV photons,
      e.g., in microbeam radiation therapy (MRT) require accurate and fast dose
      calculations for photon beams with energies between 40 and 200 keV. Multiple
      photon scattering originating from Compton scattering and the strong dependence
      of the photoelectric cross section on the atomic number of the interacting tissue
      render these dose calculations by far more challenging than the ones established
      for corresponding MeV beams. That is why so far developed analytical models of kV
      photon dose calculations fail to provide the required accuracy and one has to
      rely on time consuming Monte Carlo simulation techniques. METHODS: In this paper,
      the authors introduce a novel analytical approach for kV photon dose calculations
      with an accuracy that is almost comparable to the one of Monte Carlo simulations.
      First, analytical point dose and pencil beam kernels are derived for homogeneous
      media and compared to Monte Carlo simulations performed with the Geant4 toolkit.
      The dose contributions are systematically separated into contributions from the
      relevant orders of multiple photon scattering. Moreover, approximate scaling laws
      for the extension of the algorithm to inhomogeneous media are derived. RESULTS:
      The comparison of the analytically derived dose kernels in water showed an
      excellent agreement with the Monte Carlo method. Calculated values deviate less
      than 5% from Monte Carlo derived dose values, for doses above 1% of the maximum
      dose. The analytical structure of the kernels allows adaption to arbitrary
      materials and photon spectra in the given energy range of 40-200 keV.
      CONCLUSIONS: The presented analytical methods can be employed in a fast treatment
      planning system for MRT. In convolution based algorithms dose calculation times
      can be reduced to a few minutes.

PMID- 24320423
TI  - Sensitivity of volumetric modulated arc therapy patient specific QA results to
      multileaf collimator errors and correlation to dose volume histogram based
      metrics.
AB  - PURPOSE: This study investigates the impact of systematic multileaf collimator
      (MLC) positional errors on gamma analysis results used for quality assurance (QA)
      of Rapidarc treatments. In addition, this study evaluates the relationship of
      these gamma analysis results and clinical dose volume histogram metrics (DVH) for
      Rapidarc treatment plans. METHODS: Five prostate plans were modified by the
      introduction of systematic MLC errors. The MLC shifts to each individual active
      leaf introduced were 0.25, 0.5, 0.75, and 1 mm. All QA verification plans were
      delivered and estimated 3D patient dose or high density phantom dose were
      obtained based on the ArcCHECK measurement files. QA gamma analysis of 3%/3 mm
      and 2%/2 mm were implemented and relationships to dose differences in DVH metrics
      encountered due to MLC errors were determined. Tolerances of 3% and 5% for DVH
      metric were implemented to determine the sensitivity of gamma analysis to MLC
      errors. A calculation of sensitivity was determined from the number of incidences
      of false negative and false positive cases in gamma analysis results. RESULTS:
      The sensitivity of global gamma analysis for criteria of 3%/3 mm was 0.78 and for
      2%/2 mm was 0.82. A number of instances occurred for an acceptable VMAT QA gamma
      index which did not indicate a DVH metric dose error greater than 5%. The
      correlation between global gamma analysis using criteria 3%/3 mm and DVH metric
      dose error were all <0.8 indicating less than a strong correlation. CONCLUSIONS:
      There is a greater sensitivity for detection of dosimetric errors occurring in a
      Rapidarc plan using gamma criteria of 2%/2 mm than 3%/3 mm. However, there is
      lack of consistently strong correlation between global gamma indexes and clinical
      DVH metrics for PTV and bladder and rectum for Rapidarc plans. It is recommended
      that the sole use of gamma index for Rapidarc QA plan evaluation could be
      insufficient and a methodology for evaluation of delivered dose to patient is
      required.

PMID- 24320424
TI  - Physical and biological factors determining the effective proton range.
AB  - PURPOSE: Proton radiotherapy is rapidly becoming a standard treatment option for
      cancer. However, even though experimental data show an increase of the relative
      biological effectiveness (RBE) with depth, particularly at the distal end of the
      treatment field, a generic RBE of 1.1 is currently used in proton radiotherapy.
      This discrepancy might affect the effective penetration depth of the proton beam
      and thus the dose to the surrounding tissue and organs at risk. The purpose of
      this study was thus to analyze the impact of a tissue and dose dependent RBE of
      protons on the effective range of the proton beam in comparison to the range
      based on a generic RBE of 1.1. METHODS: Factors influencing the biologically
      effective proton range were systematically analyzed by means of treatment
      planning studies using the Local Effect Model (LEM IV) and the treatment planning
      software TRiP98. Special emphasis was put on the comparison of passive and active
      range modulation techniques. RESULTS: Beam energy, tissue type, and dose level
      significantly affected the biological extension of the treatment field at the
      distal edge. Up to 4 mm increased penetration depth as compared to the depth
      based on a constant RBE of 1.1. The extension of the biologically effective range
      strongly depends on the initial proton energy used for the most distal layer of
      the field and correlates with the width of the distal penumbra. Thus, the range
      extension, in general, was more pronounced for passive as compared to active
      range modulation systems, whereas the maximum RBE was higher for active systems.
      CONCLUSIONS: The analysis showed that the physical characteristics of the proton
      beam in terms of the width of the distal penumbra have a great impact on the RBE
      gradient and thus also the biologically effective penetration depth of the beam.

PMID- 24320425
TI  - The impact of leaf width and plan complexity on DMLC tracking of prostate
      intensity modulated arc therapy.
AB  - PURPOSE: Intensity modulated arc therapy (IMAT) is commonly used to treat
      prostate cancer. The purpose of this study was to evaluate the impact of leaf
      width and plan complexity on dynamic multileaf collimator (DMLC) tracking for
      prostate motion management during IMAT treatments. METHODS: Prostate IMAT plans
      were delivered with either a high-definition MLC (HDMLC) or a Millennium MLC (M
      MLC) (0.25 and 0.50 cm central leaf width, respectively), with and without DMLC
      tracking, to a dosimetric phantom that reproduced four prostate motion traces.
      The plan complexity was varied by applying leaf position constraints during plan
      optimization. A subset of the M-MLC plans was converted for delivery with the
      HDMLC, isolating the effect of the different leaf widths. The gamma index was
      used for evaluation. Tracking errors caused by target localization, leaf fitting,
      and leaf adjustment were analyzed. RESULTS: The gamma pass rate was significantly
      improved with DMLC tracking compared to no tracking (p < 0.001). With DMLC
      tracking, the average gamma index pass rate was 98.6% (range 94.8%-100%) with the
      HDMLC and 98.1% (range 95.4%-99.7%) with the M-MLC, using 3%, 3 mm criteria and
      the planned dose as reference. The corresponding pass rates without tracking were
      87.6% (range 76.2%-94.7%) and 91.1% (range 81.4%-97.6%), respectively. Decreased
      plan complexity improved the pass rate when static target measurements were used
      as reference, but not with the planned dose as reference. The main cause of
      tracking errors was leaf fitting errors, which were decreased by 42% by halving
      the leaf width. CONCLUSIONS: DMLC tracking successfully compensated for the
      prostate motion. The finer leaf width of the HDMLC improved the tracking accuracy
      compared to the M-MLC. The tracking improvement with limited plan complexity was
      small and not discernible when using the planned dose as reference.

PMID- 24320426
TI  - Demonstration of a software design and statistical analysis methodology with
      application to patient outcomes data sets.
AB  - PURPOSE: With emergence of clinical outcomes databases as tools utilized
      routinely within institutions, comes need for software tools to support automated
      statistical analysis of these large data sets and intrainstitutional exchange
      from independent federated databases to support data pooling. In this paper, the
      authors present a design approach and analysis methodology that addresses both
      issues. METHODS: A software application was constructed to automate analysis of
      patient outcomes data using a wide range of statistical metrics, by combining use
      of C#.Net and R code. The accuracy and speed of the code was evaluated using
      benchmark data sets. RESULTS: The approach provides data needed to evaluate
      combinations of statistical measurements for ability to identify patterns of
      interest in the data. Through application of the tools to a benchmark data set
      for dose-response threshold and to SBRT lung data sets, an algorithm was
      developed that uses receiver operator characteristic curves to identify a
      threshold value and combines use of contingency tables, Fisher exact tests, Welch
      t-tests, and Kolmogorov-Smirnov tests to filter the large data set to identify
      values demonstrating dose-response. Kullback-Leibler divergences were used to
      provide additional confirmation. CONCLUSIONS: The work demonstrates the viability
      of the design approach and the software tool for analysis of large data sets.

PMID- 24320427
TI  - Evaluation of an aSi-EPID with flattening filter free beams: applicability to the
      GLAaS algorithm for portal dosimetry and first experience for pretreatment QA of
      RapidArc.
AB  - PURPOSE: To demonstrate the feasibility of portal dosimetry with an amorphous
      silicon mega voltage imager for flattening filter free (FFF) photon beams by
      means of the GLAaS methodology and to validate it for pretreatment quality
      assurance of volumetric modulated arc therapy (RapidArc). METHODS: The GLAaS
      algorithm, developed for flattened beams, was applied to FFF beams of nominal
      energy of 6 and 10 MV generated by a Varian TrueBeam (TB). The amorphous silicon
      electronic portal imager [named mega voltage imager (MVI) on TB] was used to
      generate integrated images that were converted into matrices of absorbed dose to
      water. To enable GLAaS use under the increased dose-per-pulse and dose-rate
      conditions of the FFF beams, new operational source-detector-distance (SDD) was
      identified to solve detector saturation issues. Empirical corrections were
      defined to account for the shape of the profiles of the FFF beams to expand the
      original methodology of beam profile and arm backscattering correction. GLAaS for
      FFF beams was validated on pretreatment verification of RapidArc plans for three
      different TB linacs. In addition, the first pretreatment results from clinical
      experience on 74 arcs were reported in terms of gamma analysis. RESULTS: MVI
      saturates at 100 cm SDD for FFF beams but this can be avoided if images are
      acquired at 150 cm for all nominal dose rates of FFF beams. Rotational stability
      of the gantry-imager system was tested and resulted in a minimal apparent imager
      displacement during rotation of 0.2 +/- 0.2 mm at SDD = 150 cm. The accuracy of
      this approach was tested with three different Varian TrueBeam linacs from
      different institutes. Data were stratified per energy and machine and showed no
      dependence with beam quality and MLC model. The results from clinical
      pretreatment quality assurance, provided a gamma agreement index (GAI) in the
      field area for six and ten FFF beams of (99.8 +/- 0.3)% and (99.5 +/- 0.6)% with
      distance to agreement and dose difference criteria set to 3 mm/3% with 2 mm/2%
      thresholds, GAI resulted (95.7.0 +/- 2.3)% and (97.2 +/- 2.1)%. CONCLUSIONS: The
      GLAaS methodology, introduced in clinical practice for conventional flattened
      photon beams for machine, IMRT, and RapidArc quality assurance, was successfully
      adapted for FFF beams of Varian TrueBeam Linac. The detector saturation effects
      could be eliminated if the portal images acquired at 150 cm for all nominal dose
      rates of FFF beams.

PMID- 24320428
TI  - Daily dose monitoring with atlas-based auto-segmentation on diagnostic quality CT
      for prostate cancer.
AB  - PURPOSE: To evaluate the feasibility of daily dose monitoring using a patient
      specific atlas-based autosegmentation method on diagnostic quality verification
      images. METHODS: Seven patients, who were treated for prostate cancer with
      intensity modulated radiotherapy under daily imaging guidance of a CT-on-rails
      system, were selected for this study. The prostate, rectum, and bladder were
      manually contoured on the first six and last seven sets of daily verification
      images. For each patient, three patient specific atlases were constructed using
      manual contours from planning CT alone (1-image atlas), planning CT plus first
      three verification CTs (4-image atlas), and planning CT plus first six
      verification CTs (7-image atlas). These atlases were subsequently applied to the
      last seven verification image sets of the same patient to generate the auto
      contours. Daily dose was calculated by applying the original treatment plans to
      the daily beam isocenters. The autocontours and manual contours were compared
      geometrically using the dice similarity coefficient (DSC), and dosimetrically
      using the dose to 99% of the prostate CTV (D99) and the D5 of rectum and bladder.
      RESULTS: The DSC of the autocontours obtained with the 4-image atlases were 87.0%
      +/- 3.3%, 84.7% +/- 8.6%, and 93.6% +/- 4.3% for the prostate, rectum, and
      bladder, respectively. These indices were higher than those from the 1-image
      atlases (p < 0.01) and comparable to those from the 7-image atlases (p > 0.05).
      Daily prostate D99 of the autocontours was comparable to those of the manual
      contours (p = 0.55). For the bladder and rectum, the daily D5 were 95.5% +/- 5.9%
      and 99.1% +/- 2.6% of the planned D5 for the autocontours compared to 95.3% +/-
      6.7% (p = 0.58) and 99.8% +/- 2.3% (p < 0.01) for the manual contours.
      CONCLUSIONS: With patient specific 4-image atlases, atlas-based autosegmentation
      can adequately facilitate daily dose monitoring for prostate cancer.

PMID- 24320429
TI  - Experimental validation of the van Herk margin formula for lung radiation
      therapy.
AB  - PURPOSE: To validate the van Herk margin formula for lung radiation therapy using
      realistic dose calculation algorithms and respiratory motion modeling. The
      robustness of the margin formula against variations in lesion size, peak-to-peak
      motion amplitude, tissue density, treatment technique, and plan conformity was
      assessed, along with the margin formula assumption of a homogeneous dose
      distribution with perfect plan conformity. METHODS: 3DCRT and IMRT lung treatment
      plans were generated within the ORBIT treatment planning platform (RaySearch
      Laboratories, Sweden) on 4DCT datasets of virtual phantoms. Random and systematic
      respiratory motion induced errors were simulated using deformable registration
      and dose accumulation tools available within ORBIT for simulated cases of varying
      lesion sizes, peak-to-peak motion amplitudes, tissue densities, and plan
      conformities. A detailed comparison between the margin formula dose profile
      model, the planned dose profiles, and penumbra widths was also conducted to test
      the assumptions of the margin formula. Finally, a correction to account for
      imperfect plan conformity was tested as well as a novel application of the margin
      formula that accounts for the patient-specific motion trajectory. RESULTS: The
      van Herk margin formula ensured full clinical target volume coverage for all
      3DCRT and IMRT plans of all conformities with the exception of small lesions in
      soft tissue. No dosimetric trends with respect to plan technique or lesion size
      were observed for the systematic and random error simulations. However,
      accumulated plans showed that plan conformity decreased with increasing tumor
      motion amplitude. When comparing dose profiles assumed in the margin formula
      model to the treatment plans, discrepancies in the low dose regions were observed
      for the random and systematic error simulations. However, the margin formula
      respected, in all experiments, the 95% dose coverage required for planning target
      volume (PTV) margin derivation, as defined by the ICRU; thus, suitable PTV
      margins were estimated. The penumbra widths calculated in lung tissue for each
      plan were found to be very similar to the 6.4 mm value assumed by the margin
      formula model. The plan conformity correction yielded inconsistent results which
      were largely affected by image and dose grid resolution while the trajectory
      modified PTV plans yielded a dosimetric benefit over the standard internal target
      volumes approach with up to a 5% decrease in the V20 value. CONCLUSIONS: The
      margin formula showed to be robust against variations in tumor size and motion,
      treatment technique, plan conformity, as well as low tissue density. This was
      validated by maintaining coverage of all of the derived PTVs by 95% dose level,
      as required by the formal definition of the PTV. However, the assumption of
      perfect plan conformity in the margin formula derivation yields conservative
      margin estimation. Future modifications to the margin formula will require a
      correction for plan conformity. Plan conformity can also be improved by using the
      proposed trajectory modified PTV planning approach. This proves especially
      beneficial for tumors with a large anterior-posterior component of respiratory
      motion.

PMID- 24320430
TI  - Evaluating IMRT and VMAT dose accuracy: practical examples of failure to detect
      systematic errors when applying a commonly used metric and action levels.
AB  - PURPOSE: This study (1) examines a variety of real-world cases where systematic
      errors were not detected by widely accepted methods for IMRT/VMAT dosimetric
      accuracy evaluation, and (2) drills-down to identify failure modes and their
      corresponding means for detection, diagnosis, and mitigation. The primary goal of
      detailing these case studies is to explore different, more sensitive methods and
      metrics that could be used more effectively for evaluating accuracy of dose
      algorithms, delivery systems, and QA devices. METHODS: The authors present seven
      real-world case studies representing a variety of combinations of the treatment
      planning system (TPS), linac, delivery modality, and systematic error type. These
      case studies are typical to what might be used as part of an IMRT or VMAT
      commissioning test suite, varying in complexity. Each case study is analyzed
      according to TG-119 instructions for gamma passing rates and action levels for
      per-beam and/or composite plan dosimetric QA. Then, each case study is analyzed
      in-depth with advanced diagnostic methods (dose profile examination, EPID-based
      measurements, dose difference pattern analysis, 3D measurement-guided dose
      reconstruction, and dose grid inspection) and more sensitive metrics (2% local
      normalization/2 mm DTA and estimated DVH comparisons). RESULTS: For these case
      studies, the conventional 3%/3 mm gamma passing rates exceeded 99% for IMRT per
      beam analyses and ranged from 93.9% to 100% for composite plan dose analysis,
      well above the TG-119 action levels of 90% and 88%, respectively. However, all
      cases had systematic errors that were detected only by using advanced diagnostic
      techniques and more sensitive metrics. The systematic errors caused variable but
      noteworthy impact, including estimated target dose coverage loss of up to 5.5%
      and local dose deviations up to 31.5%. Types of errors included TPS model
      settings, algorithm limitations, and modeling and alignment of QA phantoms in the
      TPS. Most of the errors were correctable after detection and diagnosis, and the
      uncorrectable errors provided useful information about system limitations, which
      is another key element of system commissioning. CONCLUSIONS: Many forms of
      relevant systematic errors can go undetected when the currently prevalent metrics
      for IMRT/VMAT commissioning are used. If alternative methods and metrics are used
      instead of (or in addition to) the conventional metrics, these errors are more
      likely to be detected, and only once they are detected can they be properly
      diagnosed and rooted out of the system. Removing systematic errors should be a
      goal not only of commissioning by the end users but also product validation by
      the manufacturers. For any systematic errors that cannot be removed, detecting
      and quantifying them is important as it will help the physicist understand the
      limits of the system and work with the manufacturer on improvements. In summary,
      IMRT and VMAT commissioning, along with product validation, would benefit from
      the retirement of the 3%/3 mm passing rates as a primary metric of performance,
      and the adoption instead of tighter tolerances, more diligent diagnostics, and
      more thorough analysis.

PMID- 24320431
TI  - Time-resolved dose distributions to moving targets during volumetric modulated
      arc therapy with and without dynamic MLC tracking.
AB  - PURPOSE: The highly conformal doses delivered by volumetric modulated arc therapy
      (VMAT) may be compromised by intrafraction target motion. Although dynamic
      multileaf collimator (DMLC) tracking can mitigate the dosimetric impact of motion
      on the accumulated dose, residual errors still exist. The purpose of this study
      was to investigate the temporal evolution of dose errors throughout VMAT
      treatments delivered with and without DMLC tracking. METHODS: Tracking
      experiments were performed on a linear accelerator connected to prototype DMLC
      tracking software. A three-axis motion stage reproduced representative clinical
      trajectories of four lung tumors and four prostates. For each trajectory, two
      VMAT treatment plans (low and high modulation) were delivered with and without
      DMLC tracking as well as to a static phantom for reference. Dose distributions
      were measured continuously at 72 Hz using a dosimeter with biplanar diode arrays.
      During tracking, the MLC leaves were continuously refitted to the 3D target
      position measured by an electromagnetic transponder at 30 Hz. The dosimetric
      errors caused in the 32 motion experiments were quantified by a time-resolved
      3%/3 mm gamma-test. The erroneously exposed areas in treatment beam's eye view
      (BEV) caused by inadequate real-time MLC adaptation were calculated and compared
      with the time-resolved gamma failure rates. RESULTS: The transient gamma failure
      rate was on average 16.8% without tracking and 5.3% with tracking. The gamma
      failure rate correlated well with the erroneously exposed areas in BEV (mean of
      Pearson r = 0.83, p < 0.001). For the final accumulated doses, the mean gamma
      failure rate was 17.9% without tracking and 1.0% with tracking. With tracking the
      transient dose errors tended to cancel out resulting in the low mean gamma
      failure rate for the accumulated doses. CONCLUSIONS: Time-resolved measurements
      allow pinpointing of transient errors in dose during VMAT delivery as well as
      monitoring of erroneous dose evolution in key target positions. The erroneously
      exposed area in BEV was shown to be a good indicator of errors in the dose
      distribution during treatment delivery.

PMID- 24320432
TI  - Adaptation of the CVT algorithm for catheter optimization in high dose rate
      brachytherapy.
AB  - PURPOSE: An innovative, simple, and fast method to optimize the number and
      position of catheters is presented for prostate and breast high dose rate (HDR)
      brachytherapy, both for arbitrary templates or template-free implants (such as
      robotic templates). METHODS: Eight clinical cases were chosen randomly from a
      bank of patients, previously treated in our clinic to test our method. The 2D
      Centroidal Voronoi Tessellations (CVT) algorithm was adapted to distribute
      catheters uniformly in space, within the maximum external contour of the planning
      target volume. The catheters optimization procedure includes the inverse planning
      simulated annealing algorithm (IPSA). Complete treatment plans can then be
      generated from the algorithm for different number of catheters. The best plan is
      chosen from different dosimetry criteria and will automatically provide the
      number of catheters and their positions. After the CVT algorithm parameters were
      optimized for speed and dosimetric results, it was validated against prostate
      clinical cases, using clinically relevant dose parameters. The robustness to
      implantation error was also evaluated. Finally, the efficiency of the method was
      tested in breast interstitial HDR brachytherapy cases. RESULTS: The effect of the
      number and locations of the catheters on prostate cancer patients was studied.
      Treatment plans with a better or equivalent dose distributions could be obtained
      with fewer catheters. A better or equal prostate V100 was obtained down to 12
      catheters. Plans with nine or less catheters would not be clinically acceptable
      in terms of prostate V100 and D90. Implantation errors up to 3 mm were acceptable
      since no statistical difference was found when compared to 0 mm error (p > 0.05).
      No significant difference in dosimetric indices was observed for the different
      combination of parameters within the CVT algorithm. A linear relation was found
      between the number of random points and the optimization time of the CVT
      algorithm. Because the computation time decrease with the number of points and
      that no effects were observed on the dosimetric indices when varying the number
      of sampling points and the number of iterations, they were respectively fixed to
      2500 and to 100. The computation time to obtain ten complete treatments plans
      ranging from 9 to 18 catheters, with the corresponding dosimetric indices, was 90
      s. However, 93% of the computation time is used by a research version of IPSA.
      For the breast, on average, the Radiation Therapy Oncology Group recommendations
      would be satisfied down to 12 catheters. Plans with nine or less catheters would
      not be clinically acceptable in terms of V100, dose homogeneity index, and D90.
      CONCLUSIONS: The authors have devised a simple, fast and efficient method to
      optimize the number and position of catheters in interstitial HDR brachytherapy.
      The method was shown to be robust for both prostate and breast HDR brachytherapy.
      More importantly, the computation time of the algorithm is acceptable for
      clinical use. Ultimately, this catheter optimization algorithm could be coupled
      with a 3D ultrasound system to allow real-time guidance and planning in HDR
      brachytherapy.

PMID- 24320433
TI  - Is ExacTrac x-ray system an alternative to CBCT for positioning patients with
      head and neck cancers?
AB  - PURPOSE: To evaluate the usefulness of a six-degrees-of freedom (6D) correction
      using ExacTrac robotics system in patients with head-and-neck (HN) cancer
      receiving radiation therapy. METHODS: Local setup accuracy was analyzed for 12
      patients undergoing intensity-modulated radiation therapy (IMRT). Patient
      position was imaged daily upon two different protocols, cone-beam computed
      tomography (CBCT), and ExacTrac (ET) images correction. Setup data from either
      approach were compared in terms of both residual errors after correction and
      punctual displacement of selected regions of interest (Mandible, C2, and C6
      vertebral bodies). RESULTS: On average, both protocols achieved reasonably low
      residual errors after initial correction. The observed differences in shift
      vectors between the two protocols showed that CBCT tends to weight more C2 and C6
      at the expense of the mandible, while ET tends to average more differences among
      the different ROIs. CONCLUSIONS: CBCT, even without 6D correction capabilities,
      seems preferable to ET for better consistent alignment and the capability to see
      soft tissues. Therefore, in our experience, CBCT represents a benchmark for
      positioning head and neck cancer patients.

PMID- 24320434
TI  - Spatial frequency spectrum of the x-ray scatter distribution in CBCT projections.
AB  - PURPOSE: X-ray scatter is a source of significant image quality loss in cone-beam
      computed tomography (CBCT). The use of Monte Carlo (MC) simulations separating
      primary and scattered photons has allowed the structure and nature of the scatter
      distribution in CBCT to become better elucidated. This work seeks to quantify the
      structure and determine a suitable basis function for the scatter distribution by
      examining its spectral components using Fourier analysis. METHODS: The scatter
      distribution projection data were simulated using a CBCT MC model based on the
      EGSnrc code. CBCT projection data, with separated primary and scatter signal,
      were generated for a 30.6 cm diameter water cylinder [single angle projection
      with varying axis-to-detector distance (ADD) and bowtie filters] and two
      anthropomorphic phantoms (head and pelvis, 360 projections sampled every 1
      degrees , with and without a compensator). The Fourier transform of the resulting
      scatter distributions was computed and analyzed both qualitatively and
      quantitatively. A novel metric called the scatter frequency width (SFW) is
      introduced to determine the scatter distribution's frequency content. The
      frequency content results are used to determine a set basis functions, consisting
      of low-frequency sine and cosine functions, to fit and denoise the scatter
      distribution generated from MC simulations using a reduced number of photons and
      projections. The signal recovery is implemented using Fourier filtering (low-pass
      Butterworth filter) and interpolation. Estimates of the scatter distribution are
      used to correct and reconstruct simulated projections. RESULTS: The spatial and
      angular frequencies are contained within a maximum frequency of 0.1 cm(-1) and
      7/(2pi) rad(-1) for the imaging scenarios examined, with these values varying
      depending on the object and imaging setup (e.g., ADD and compensator). These data
      indicate spatial and angular sampling every 5 cm and pi/7 rad (~25 degrees ) can
      be used to properly capture the scatter distribution, with reduced sampling
      possible depending on the imaging scenario. Using a low-pass Butterworth filter,
      tuned with the SFW values, to denoise the scatter projection data generated from
      MC simulations using 10(6) photons resulted in an error reduction of greater than
      85% for the estimating scatter in single and multiple projections. Analysis
      showed that the use of a compensator helped reduce the error in estimating the
      scatter distribution from limited photon simulations by more than 37% when
      compared to the case without a compensator for the head and pelvis phantoms.
      Reconstructions of simulated head phantom projections corrected by the filtered
      and interpolated scatter estimates showed improvements in overall image quality.
      CONCLUSIONS: The spatial frequency content of the scatter distribution in CBCT is
      found to be contained within the low frequency domain. The frequency content is
      modulated both by object and imaging parameters (ADD and compensator). The low
      frequency nature of the scatter distribution allows for a limited set of sine and
      cosine basis functions to be used to accurately represent the scatter signal in
      the presence of noise and reduced data sampling decreasing MC based scatter
      estimation time. Compensator induced modulation of the scatter distribution
      reduces the frequency content and improves the fitting results.

PMID- 24320435
TI  - Volumetric quantification of lung nodules in CT with iterative reconstruction
      (ASiR and MBIR).
AB  - PURPOSE: Volume quantifications of lung nodules with multidetector computed
      tomography (CT) images provide useful information for monitoring nodule
      developments. The accuracy and precision of the volume quantification, however,
      can be impacted by imaging and reconstruction parameters. This study aimed to
      investigate the impact of iterative reconstruction algorithms on the accuracy and
      precision of volume quantification with dose and slice thickness as additional
      variables. METHODS: Repeated CT images were acquired from an anthropomorphic
      chest phantom with synthetic nodules (9.5 and 4.8 mm) at six dose levels, and
      reconstructed with three reconstruction algorithms [filtered backprojection
      (FBP), adaptive statistical iterative reconstruction (ASiR), and model based
      iterative reconstruction (MBIR)] into three slice thicknesses. The nodule volumes
      were measured with two clinical software (A: Lung VCAR, B: iNtuition), and
      analyzed for accuracy and precision. RESULTS: Precision was found to be generally
      comparable between FBP and iterative reconstruction with no statistically
      significant difference noted for different dose levels, slice thickness, and
      segmentation software. Accuracy was found to be more variable. For large nodules,
      the accuracy was significantly different between ASiR and FBP for all slice
      thicknesses with both software, and significantly different between MBIR and FBP
      for 0.625 mm slice thickness with Software A and for all slice thicknesses with
      Software B. For small nodules, the accuracy was more similar between FBP and
      iterative reconstruction, with the exception of ASIR vs FBP at 1.25 mm with
      Software A and MBIR vs FBP at 0.625 mm with Software A. CONCLUSIONS: The
      systematic difference between the accuracy of FBP and iterative reconstructions
      highlights the importance of extending current segmentation software to
      accommodate the image characteristics of iterative reconstructions. In addition,
      a calibration process may help reduce the dependency of accuracy on
      reconstruction algorithms, such that volumes quantified from scans of different
      reconstruction algorithms can be compared. The little difference found between
      the precision of FBP and iterative reconstructions could be a result of both
      iterative reconstruction's diminished noise reduction at the edge of the nodules
      as well as the loss of resolution at high noise levels with iterative
      reconstruction. The findings do not rule out potential advantage of IR that might
      be evident in a study that uses a larger number of nodules or repeated scans.

PMID- 24320436
TI  - Utility as a rationale for choosing observer performance assessment paradigms for
      detection tasks in medical imaging.
AB  - PURPOSE: Studies of lesion detectability are often carried out to evaluate
      medical imaging technology. For such studies, several approaches have been
      proposed to measure observer performance, such as the receiver operating
      characteristic (ROC), the localization ROC (LROC), the free-response ROC (FROC),
      the alternative free-response ROC (AFROC), and the exponentially transformed FROC
      (EFROC) paradigms. Therefore, an experimenter seeking to carry out such a study
      is confronted with an array of choices. Traditionally, arguments for different
      approaches have been made on the basis of practical considerations (statistical
      power, etc.) or the gross level of analysis (case-level or lesion-level). This
      article contends that a careful consideration of utility should form the
      rationale for matching the assessment paradigm to the clinical task of interest.
      METHODS: In utility theory, task performance is commonly evaluated with total
      expected utility, which integrates the various event utilities against the
      probability of each event. To formalize the relationship between expected utility
      and the summary curve associated with each assessment paradigm, the concept of a
      "natural" utility structure is proposed. A natural utility structure is defined
      for a summary curve when the variables associated with the summary curve axes are
      sufficient for computing total expected utility, assuming that the disease
      prevalence is known. RESULTS: Natural utility structures for ROC, LROC, FROC,
      AFROC, and EFROC curves are introduced, clarifying how the utilities of correct
      and incorrect decisions are aggregated by summary curves. Further, conditions are
      given under which general utility structures for localization-based methodologies
      reduce to case-based assessment. CONCLUSIONS: Overall, the findings reveal how
      summary curves correspond to natural utility structures of diagnostic tasks,
      suggesting utility as a motivating principle for choosing an assessment paradigm.

PMID- 24320437
TI  - Fully 3D iterative CT reconstruction using polar coordinates.
AB  - PURPOSE: This paper demonstrates the feasibility of fully 3D iterative computed
      tomography reconstruction of highly resolved fields of view using polar
      coordinates. METHODS: System matrix is computed using a ray-tracing approach in
      cylindrical or spherical coordinates. By using polar symmetries inherent to the
      acquisition geometry, the system matrix size can be reduced by a factor
      corresponding to the number of acquired projections. Such an important decrease
      in size allows the system matrix to be precomputed, and loaded all at once into
      memory prior to reconstruction. By carefully ordering the field of view voxels
      and the sinogram data, reconstruction speed is also enhanced by a cache-oblivious
      computer implementation. The reconstruction algorithm is also compatible with the
      ordered-subsets acceleration method. A final polar-to-Cartesian transformation is
      applied to the reconstructed image in order to allow proper visualization.
      RESULTS: The ray-tracing and reconstruction algorithms were implemented in polar
      representation. Large 3D system matrices were calculated in cylindrical and
      spherical coordinates, and the performance assessed against Cartesian ray-tracers
      in terms of speed and memory requirements. Images of analytical phantoms were
      successfully reconstructed in both cylindrical and spherical coordinates. Fully
      3D images of phantoms and small animals were acquired with a Gamma Medica Triumph
      X-O small animal CT scanner and reconstructed using the manufacturer's software
      and the proposed polar approach to demonstrate the accuracy and robustness of the
      later. The noise was found to be reduced while preserving the same level of
      spatial resolution, without noticeable polar artifacts. CONCLUSIONS: Under a
      reasonable set of assumptions, the memory size of the system matrix can be
      reduced by a factor corresponding to the number of projections. Using this
      strategy, iterative reconstruction from high resolution clinical and preclinical
      systems can be more easily performed using general-purpose personal computers.

PMID- 24320438
TI  - Correlation between human observer performance and model observer performance in
      differential phase contrast CT.
AB  - PURPOSE: With the recently expanding interest and developments in x-ray
      differential phase contrast CT (DPC-CT), the evaluation of its task-specific
      detection performance and comparison with the corresponding absorption CT under a
      given radiation dose constraint become increasingly important. Mathematical model
      observers are often used to quantify the performance of imaging systems, but
      their correlations with actual human observers need to be confirmed for each new
      imaging method. This work is an investigation of the effects of stochastic DPC-CT
      noise on the correlation of detection performance between model and human
      observers with signal-known-exactly (SKE) detection tasks. METHODS: The
      detectabilities of different objects (five disks with different diameters and two
      breast lesion masses) embedded in an experimental DPC-CT noise background were
      assessed using both model and human observers. The detectability of the disk and
      lesion signals was then measured using five types of model observers including
      the prewhitening ideal observer, the nonprewhitening (NPW) observer, the
      nonprewhitening observer with eye filter and internal noise (NPWEi), the
      prewhitening observer with eye filter and internal noise (PWEi), and the
      channelized Hotelling observer (CHO). The same objects were also evaluated by
      four human observers using the two-alternative forced choice method. The results
      from the model observer experiment were quantitatively compared to the human
      observer results to assess the correlation between the two techniques. RESULTS:
      The contrast-to-detail (CD) curve generated by the human observers for the disk
      detection experiments shows that the required contrast to detect a disk is
      inversely proportional to the square root of the disk size. Based on the CD
      curves, the ideal and NPW observers tend to systematically overestimate the
      performance of the human observers. The NPWEi and PWEi observers did not predict
      human performance well either, as the slopes of their CD curves tended to be
      steeper. The CHO generated the best quantitative agreement with human observers
      with its CD curve overlapping with that of human observer. Statistical
      equivalence between CHO and humans can be claimed within 11% of the human
      observer results, including both the disk and lesion detection experiments.
      CONCLUSIONS: The model observer method can be used to accurately represent human
      observer performance with the stochastic DPC-CT noise for SKE tasks with sizes
      ranging from 8 to 128 pixels. The incorporation of the anatomical noise remains
      to be studied.

PMID- 24320439
TI  - Urinary bladder segmentation in CT urography (CTU) using CLASS.
AB  - PURPOSE: The authors are developing a computerized system for bladder
      segmentation on CTU, as a critical component for computer aided diagnosis of
      bladder cancer. METHODS: A challenge for bladder segmentation is the presence of
      regions without contrast (NC) and filled with intravenous contrast (C). The
      authors have designed a Conjoint Level set Analysis and Segmentation System
      (CLASS) specifically for this application. CLASS performs a series of image
      processing tasks: preprocessing, initial segmentation, 3D and 2D level set
      segmentation, and postprocessing, designed according to the characteristics of
      the bladder in CTU. The NC and the C regions of the bladder were segmented
      separately in CLASS. The final contour is obtained in the postprocessing stage by
      the union of the NC and C contours. With Institutional Review Board (IRB)
      approval, the authors retrospectively collected 81 CTU scans, in which 40
      bladders contained lesions, 26 contained diffuse wall thickening, and 15 were
      considered to be normal. The bladders were segmented by CLASS and the performance
      was assessed by rating the quality of the contours on a 10-point scale (1 = "very
      poor," 5 = "fair," 10 = "perfect"). For 30 bladders, 3D hand-segmented contours
      were obtained and the segmentation accuracy of CLASS was evaluated and compared
      to that of a single level set method in terms of the average minimum distance,
      average volume intersection ratio, average volume error and Jaccard index.
      RESULTS: Of the 81 bladders, the average quality rating for CLASS was 6.5 +/-
      1.3. Thirty nine bladders were given quality ratings of 7 or above. Only five
      bladders had ratings under 5. The average minimum distance, average volume
      intersection ratio, average volume error, and average Jaccard index for CLASS
      were 3.5 +/- 1.3 mm, (79.0 +/- 8.2)%, (16.1 +/- 16.3)%, and (75.7 +/- 8.4)%,
      respectively, and for the single level set method were 5.2 +/- 2.6 mm, (78.8 +/-
      16.3)%, (8.3 +/- 33.1)%, (71.0 +/- 15.4)%, respectively. CONCLUSIONS: The results
      demonstrate the potential of CLASS for segmentation of the bladder.

PMID- 24320440
TI  - Development and validation of a measurement-based source model for kilovoltage
      cone-beam CT Monte Carlo dosimetry simulations.
AB  - PURPOSE: The purpose of this study is to adapt an equivalent source model
      originally developed for conventional CT Monte Carlo dose quantification to the
      radiation oncology context and validate its application for evaluating
      concomitant dose incurred by a kilovoltage (kV) cone-beam CT (CBCT) system
      integrated into a linear accelerator. METHODS: In order to properly characterize
      beams from the integrated kV CBCT system, the authors have adapted a previously
      developed equivalent source model consisting of an equivalent spectrum module
      that takes into account intrinsic filtration and an equivalent filter module
      characterizing the added bowtie filtration. An equivalent spectrum was generated
      for an 80, 100, and 125 kVp beam with beam energy characterized by half-value
      layer measurements. An equivalent filter description was generated from bowtie
      profile measurements for both the full- and half-bowtie. Equivalent source models
      for each combination of equivalent spectrum and filter were incorporated into the
      Monte Carlo software package MCNPX. Monte Carlo simulations were then validated
      against in-phantom measurements for both the radiographic and CBCT mode of
      operation of the kV CBCT system. Radiographic and CBCT imaging dose was measured
      for a variety of protocols at various locations within a body (32 cm in diameter)
      and head (16 cm in diameter) CTDI phantom. The in-phantom radiographic and CBCT
      dose was simulated at all measurement locations and converted to absolute dose
      using normalization factors calculated from air scan measurements and
      corresponding simulations. The simulated results were compared with the physical
      measurements and their discrepancies were assessed quantitatively. RESULTS:
      Strong agreement was observed between in-phantom simulations and measurements.
      For the radiographic protocols, simulations uniformly underestimated measurements
      by 0.54%-5.14% (mean difference = -3.07%, SD = 1.60%). For the CBCT protocols,
      simulations uniformly underestimated measurements by 1.35%-5.31% (mean difference
      = -3.42%, SD = 1.09%). CONCLUSIONS: This work demonstrates the feasibility of
      using a measurement-based kV CBCT source model to facilitate dose calculations
      with Monte Carlo methods for both the radiographic and CBCT mode of operation.
      While this initial work validates simulations against measurements for simple
      geometries, future work will involve utilizing the source model to investigate kV
      CBCT dosimetry with more complex anthropomorphic phantoms and patient specific
      models.

PMID- 24320441
TI  - CT image assessment by low contrast signal detectability evaluation with unknown
      signal location.
AB  - PURPOSE: To devise a new methodology for CT image quality evaluation in order to
      assess the dose reduction potential of new iterative reconstruction algorithms
      (IRA). METHODS: Because of the nonlinear behavior of IRA, the authors propose a
      task-based methodology consisting of measuring the detectability of small, low
      contrast signals at random locations. The authors test, via simulations, a
      phantom design that facilitates human and numerical observer studies in such
      conditions. The setup allows for the random selection of regions of interest
      (ROI) around each signal, so that the relative signal location is unknown if the
      ROIs are shown separately. With such a setup one can perform signal detectability
      measurements with a variety of image reading arrangements and data analysis
      methods. In this work, the authors demonstrate the use of the localization
      relative operating characteristic method. The phantom design also allows for
      efficient image evaluation utilizing an automatic signal search technique and a
      recently developed nonparametric data analysis method using the exponential
      transformation of the free response characteristic curve. RESULTS: The authors
      present the application of these methods by performing a comparison between the
      filtered back projection (FBP) algorithm and a polychromatic iterative image
      reconstruction algorithm. In this generic illustration of the image evaluation
      framework, the expected improved performance of the IRA over FBP is confirmed.
      CONCLUSIONS: The results demonstrate the ability of these methods to determine
      signal detectability indices with good accuracy with only a small number, of the
      order of a few tens, of image samples.

PMID- 24320442
TI  - Dimensionality and noise in energy selective x-ray imaging.
AB  - PURPOSE: To develop and test a method to quantify the effect of dimensionality on
      the noise in energy selective x-ray imaging. METHODS: The Cramer-Rao lower bound
      (CRLB), a universal lower limit of the covariance of any unbiased estimator, is
      used to quantify the noise. It is shown that increasing dimensionality always
      increases, or at best leaves the same, the variance. An analytic formula for the
      increase in variance in an energy selective x-ray system is derived. The formula
      is used to gain insight into the dependence of the increase in variance on the
      properties of the additional basis functions, the measurement noise covariance,
      and the source spectrum. The formula is also used with computer simulations to
      quantify the dependence of the additional variance on these factors. Simulated
      images of an object with three materials are used to demonstrate the trade-off of
      increased information with dimensionality and noise. The images are computed from
      energy selective data with a maximum likelihood estimator. RESULTS: The increase
      in variance depends most importantly on the dimension and on the properties of
      the additional basis functions. With the attenuation coefficients of cortical
      bone, soft tissue, and adipose tissue as the basis functions, the increase in
      variance of the bone component from two to three dimensions is 1.4 * 10(3). With
      the soft tissue component, it is 2.7 * 10(4). If the attenuation coefficient of a
      high atomic number contrast agent is used as the third basis function, there is
      only a slight increase in the variance from two to three basis functions, 1.03
      and 7.4 for the bone and soft tissue components, respectively. The changes in
      spectrum shape with beam hardening also have a substantial effect. They increase
      the variance by a factor of approximately 200 for the bone component and 220 for
      the soft tissue component as the soft tissue object thickness increases from 1 to
      30 cm. Decreasing the energy resolution of the detectors increases the variance
      of the bone component markedly with three dimension processing, approximately a
      factor of 25 as the resolution decreases from 100 to 3 bins. The increase with
      two dimension processing for adipose tissue is a factor of two and with the
      contrast agent as the third material for two or three dimensions is also a factor
      of two for both components. The simulated images show that a maximum likelihood
      estimator can be used to process energy selective x-ray data to produce images
      with noise close to the CRLB. CONCLUSIONS: The method presented can be used to
      compute the effects of the object attenuation coefficients and the x-ray system
      properties on the relationship of dimensionality and noise in energy selective x
      ray imaging systems.

PMID- 24320443
TI  - Development of novel imaging probe for optical/acoustic radiation imaging (OARI).
AB  - PURPOSE: Optical/acoustic radiation imaging (OARI) is a novel imaging modality
      being developed to interrogate the optical and mechanical properties of soft
      tissues. OARI uses acoustic radiation force to generate displacement in soft
      tissue. Optical images before and after the application of the force are used to
      generate displacement maps that provide information about the mechanical
      properties of the tissue under interrogation. Since the images are optical
      images, they also represent the optical properties of the tissue as well. In this
      paper, the authors present the first imaging probe that uses acoustic radiation
      force in conjunction with optical coherence tomography (OCT) to provide
      information about the optical and mechanical properties of tissues to assist in
      the diagnosis and staging of epithelial cancers, and in particular bladder
      cancer. METHODS: The OARI prototype probe consisted of an OCT probe encased in a
      plastic sheath, a miniaturized transducer glued to a plastic holder, both of
      which were encased in a 10 cm stainless steel tube with an inner diameter of 10
      mm. The transducer delivered an acoustic intensity of 18 W/cm(2) and the OCT
      probe had a spatial resolution of approximately 10-20 MUm. The tube was filled
      with deionized water for acoustic coupling and covered by a low density
      polyethylene cap. The OARI probe was characterized and tested on bladder wall
      phantoms. The phantoms possessed Young's moduli ranging from 10.2 to 12 kPa, mass
      density of 1.05 g/cm(3), acoustic attenuation coefficient of 0.66 dB/cm MHz,
      speed of sound of 1591 m/s, and optical scattering coefficient of 1.80 mm(-1).
      Finite element model (FEM) theoretical simulations were performed to assess the
      performance of the OARI probe. RESULTS: The authors obtained displacements of
      9.4, 8.7, and 3.4 MUm for the 3%, 4%, and 5% bladder wall phantoms, respectively.
      This shows that the probe is capable of generating optical images, and also has
      the ability to generate and track displacements in tissue. This will provide
      information about the optical and mechanical properties of the tissue to assist
      in epithelial cancer detection. The corresponding theoretical FEM displacement
      was 5.8, 5.4, and 5.0 MUm for the 3%, 4%, and 5% phantoms, respectively.
      Deviation between OARI displacement and FEM displacement is due to the resolution
      of the crosscorrelation algorithm used to track the displacement. To the authors'
      knowledge, this is the first probe that successfully combines OCT with a source
      of acoustic radiation force. CONCLUSIONS: The OARI probe has the ability to
      provide information about the mechanical and optical properties of phantoms and
      soft tissue. This could prove useful in early epithelial cancer detection.
      Because the probe is 10 mm in diameter, it is currently only useful for skin and
      oral applications. The probe would have to be reduced in size to make it
      applicable for cancer detection in other internal sites. Future work will focus
      on utilizing phase-sensitive optical coherence elastography to obtain the
      resulting OARI displacements, improving the resolution of the probe, and enable
      physicians to better evaluate the mechanical properties of soft tissues.

PMID- 24320444
TI  - Oblique reconstructions in tomosynthesis. I. Linear systems theory.
AB  - PURPOSE: By convention, slices in a tomosynthesis reconstruction are created on
      planes parallel to the detector. It has not yet been demonstrated that slices can
      be generated along oblique directions through the same volume, analogous to
      multiplanar reconstructions in computed tomography (CT). The purpose of this work
      is to give a proof-of-principle justification for oblique reconstructions in
      tomosynthesis, which acquires projection images over a smaller angular range than
      CT. METHODS: To investigate the visibility of individual frequencies in an
      oblique reconstruction, a theoretical framework is developed in which the
      reconstruction of a sinusoidal input is calculated. The test frequency is pitched
      at an angle in a 2D parallel-beam acquisition geometry. Reconstructions are
      evaluated along the pitch of the object. The modulation transfer function (MTF)
      is calculated from the relative signal at various test frequencies. The MTF
      determines whether modulation is within detectable limits in oblique
      reconstructions. In the previous linear systems (LS) model [B. Zhao and W. Zhao,
      "Three-dimensional linear system analysis for breast tomosynthesis," Med. Phys.
      35(12), 5219-5232 (2008)], the MTF was calculated only in reconstructed slices
      parallel to the detector. This paper generalizes the MTF calculation to
      reconstructed slices at all possible pitches. Unlike the previous LS model, this
      paper also analyzes the effect of object thickness on the MTF. A second test
      object that is considered is a rod whose long axis is pitched similar to the
      sinusoidal input. The rod is used to assess whether the length of an object can
      be correctly estimated in oblique reconstructions. RESULTS: To simulate the
      conventional display of the reconstruction, slices are first created along a 0
      degrees  pitch. This direction is perpendicular to the rays of the central
      projection. The authors show that the input frequency of a pitched sinusoidal
      object cannot be determined using these slices. By changing the pitch of the
      slice to match the object, it is shown that the input frequency is properly
      resolved. To prove that modulation is preserved in pitched slices, the MTF is
      also calculated. Modulation is within detectable limits over a broad range of
      pitches if the object is thin, but is detectable over a narrower range of pitches
      if the object is thick. Turning next to the second test object, it is shown that
      the length of a pitched rod can be correctly determined in oblique
      reconstructions. Concordant with the behavior of the MTF, the length estimate is
      accurate over a broad range of pitches if the object is thin, but is correct over
      a narrower range of pitches if the object is thick. CONCLUSIONS: This work
      justifies the feasibility of oblique reconstructions in tomosynthesis. It is
      demonstrated that pitched test objects are most easily visualized with oblique
      reconstructions instead of conventional reconstructions. In order to achieve high
      image quality over a broad range of pitches, the object must be thin. By
      analyzing the effect of reconstruction pitch and object thickness on image
      quality, this paper generalizes the previous LS model for tomosynthesis.

PMID- 24320445
TI  - Oblique reconstructions in tomosynthesis. II. Super-resolution.
AB  - PURPOSE: In tomosynthesis, super-resolution has been demonstrated using
      reconstruction planes parallel to the detector. Super-resolution allows for
      subpixel resolution relative to the detector. The purpose of this work is to
      develop an analytical model that generalizes super-resolution to oblique
      reconstruction planes. METHODS: In a digital tomosynthesis system, a sinusoidal
      test object is modeled along oblique angles (i.e., "pitches") relative to the
      plane of the detector in a 3D divergent-beam acquisition geometry. To investigate
      the potential for super-resolution, the input frequency is specified to be
      greater than the alias frequency of the detector. Reconstructions are evaluated
      in an oblique plane along the extent of the object using simple backprojection
      (SBP) and filtered backprojection (FBP). By comparing the amplitude of the
      reconstruction against the attenuation coefficient of the object at various
      frequencies, the modulation transfer function (MTF) is calculated to determine
      whether modulation is within detectable limits for super-resolution. For
      experimental validation of super-resolution, a goniometry stand was used to
      orient a bar pattern phantom along various pitches relative to the breast support
      in a commercial digital breast tomosynthesis system. RESULTS: Using theoretical
      modeling, it is shown that a single projection image cannot resolve a sine input
      whose frequency exceeds the detector alias frequency. The high frequency input is
      correctly visualized in SBP or FBP reconstruction using a slice along the pitch
      of the object. The Fourier transform of this reconstructed slice is maximized at
      the input frequency as proof that the object is resolved. Consistent with the
      theoretical results, experimental images of a bar pattern phantom showed super
      resolution in oblique reconstructions. At various pitches, the highest frequency
      with detectable modulation was determined by visual inspection of the bar
      patterns. The dependency of the highest detectable frequency on pitch followed
      the same trend as the analytical model. It was demonstrated that super-resolution
      is not achievable if the pitch of the object approaches 90 degrees ,
      corresponding to the case in which the test frequency is perpendicular to the
      breast support. Only low frequency objects are detectable at pitches close to 90
      degrees . CONCLUSIONS: This work provides a platform for investigating super
      resolution in oblique reconstructions for tomosynthesis. In breast imaging, this
      study should have applications in visualizing microcalcifications and other
      subtle signs of cancer.

PMID- 24320446
TI  - Design optimization of MR-compatible rotating anode x-ray tubes for stable
      operation.
AB  - PURPOSE: Hybrid x-ray/MR systems can enhance the diagnosis and treatment of
      endovascular, cardiac, and neurologic disorders by using the complementary
      advantages of both modalities for image guidance during interventional
      procedures. Conventional rotating anode x-ray tubes fail near an MR imaging
      system, since MR fringe fields create eddy currents in the metal rotor which
      cause a reduction in the rotation speed of the x-ray tube motor. A new x-ray tube
      motor prototype has been designed and built to be operated close to a magnet. To
      ensure the stability and safety of the motor operation, dynamic characteristics
      must be analyzed to identify possible modes of mechanical failure. In this study
      a 3D finite element method (FEM) model was developed in order to explore possible
      modifications, and to optimize the motor design. The FEM provides a valuable tool
      that permits testing and evaluation using numerical simulation instead of
      building multiple prototypes. METHODS: Two experimental approaches were used to
      measure resonance characteristics: the first obtained the angular speed curves of
      the x-ray tube motor employing an angle encoder; the second measured the power
      spectrum using a spectrum analyzer, in which the large amplitude of peaks
      indicates large vibrations. An estimate of the bearing stiffness is required to
      generate an accurate FEM model of motor operation. This stiffness depends on both
      the bearing geometry and adjacent structures (e.g., the number of balls,
      clearances, preload, etc.) in an assembly, and is therefore unknown. This
      parameter was set by matching the FEM results to measurements carried out with
      the anode attached to the motor, and verified by comparing FEM predictions and
      measurements with the anode removed. The validated FEM model was then used to
      sweep through design parameters [bearing stiffness (1 * 10(5)-5 * 10(7) N/m),
      shaft diameter (0.372-0.625 in.), rotor diameter (2.4-2.9 in.), and total length
      of motor (5.66-7.36 in.)] to increase the fundamental frequency past the
      operating range at 50 Hz. RESULTS: The first large vibration during the prototype
      motor operation was obtained at 21.64 +/- 0.68 Hz in the power spectrum. An
      abrupt decrease in acceleration occurred at 21.5 Hz due to struggling against the
      resonance vibrations. A bearing stiffness of 1.2 * 10(5) N/m in the FEM
      simulation was used to obtain a critical speed of 21.4 Hz providing 1.1% error.
      This bearing stiffness value and the 3D model were then confirmed by the
      experiments with the anode removed, demonstrating an agreement within 6.4%
      between simulation results and measurements. A calculated first critical
      frequency (fundamental frequency) of 68.5 Hz was obtained by increasing the
      bearing stiffness to 1 * 10(7) N/m and increasing the shaft diameter by 68.0%.
      Reducing the number of bearings in the design permits decreasing the total length
      of the motor by 1.7 in., and results in a fundamental frequency of 68.3 Hz in
      concert with additional changes (shaft diameter of 0.625 in., rotor diameter of
      2.4 in., and bearing stiffness of 1 * 10(6) N/m). CONCLUSIONS: An FEM model of
      the x-ray tube motor has been implemented and experimentally validated. A
      fundamental frequency above the operational rotation speed can be achieved
      through modification of multiple design parameters, which allows the motor to
      operate stably and safely in the MR environment during the repeated
      acceleration/deceleration cycles required for an interventional procedure. The
      validated 3D FEM model can now be used to investigate trade-offs between
      generated torque, maximum speed, and motor inertia to further optimize motor
      design.

PMID- 24320447
TI  - CONRAD--a software framework for cone-beam imaging in radiology.
AB  - PURPOSE: In the community of x-ray imaging, there is a multitude of tools and
      applications that are used in scientific practice. Many of these tools are
      proprietary and can only be used within a certain lab. Often the same algorithm
      is implemented multiple times by different groups in order to enable comparison.
      In an effort to tackle this problem, the authors created CONRAD, a software
      framework that provides many of the tools that are required to simulate basic
      processes in x-ray imaging and perform image reconstruction with consideration of
      nonlinear physical effects. METHODS: CONRAD is a Java-based state-of-the-art
      software platform with extensive documentation. It is based on platform
      independent technologies. Special libraries offer access to hardware acceleration
      such as OpenCL. There is an easy-to-use interface for parallel processing. The
      software package includes different simulation tools that are able to generate up
      to 4D projection and volume data and respective vector motion fields. Well known
      reconstruction algorithms such as FBP, DBP, and ART are included. All algorithms
      in the package are referenced to a scientific source. RESULTS: A total of 13
      different phantoms and 30 processing steps have already been integrated into the
      platform at the time of writing. The platform comprises 74.000 nonblank lines of
      code out of which 19% are used for documentation. The software package is
      available for download at http://conrad.stanford.edu. To demonstrate the use of
      the package, the authors reconstructed images from two different scanners, a
      table top system and a clinical C-arm system. Runtimes were evaluated using the
      RabbitCT platform and demonstrate state-of-the-art runtimes with 2.5 s for the
      256 problem size and 12.4 s for the 512 problem size. CONCLUSIONS: As a common
      software framework, CONRAD enables the medical physics community to share
      algorithms and develop new ideas. In particular this offers new opportunities for
      scientific collaboration and quantitative performance comparison between the
      methods of different groups.

PMID- 24320448
TI  - Effects of sparse sampling schemes on image quality in low-dose CT.
AB  - PURPOSE: Various scanning methods and image reconstruction algorithms are
      actively investigated for low-dose computed tomography (CT) that can potentially
      reduce a health-risk related to radiation dose. Particularly, compressive-sensing
      (CS) based algorithms have been successfully developed for reconstructing images
      from sparsely sampled data. Although these algorithms have shown promises in low
      dose CT, it has not been studied how sparse sampling schemes affect image quality
      in CS-based image reconstruction. In this work, the authors present several
      sparse-sampling schemes for low-dose CT, quantitatively analyze their data
      property, and compare effects of the sampling schemes on the image quality.
      METHODS: Data properties of several sampling schemes are analyzed with respect to
      the CS-based image reconstruction using two measures: sampling density and data
      incoherence. The authors present five different sparse sampling schemes, and
      simulated those schemes to achieve a targeted dose reduction. Dose reduction
      factors of about 75% and 87.5%, compared to a conventional scan, were tested. A
      fully sampled circular cone-beam CT data set was used as a reference, and sparse
      sampling has been realized numerically based on the CBCT data. RESULTS: It is
      found that both sampling density and data incoherence affect the image quality in
      the CS-based reconstruction. Among the sampling schemes the authors investigated,
      the sparse-view, many-view undersampling (MVUS)-fine, and MVUS-moving cases have
      shown promising results. These sampling schemes produced images with similar
      image quality compared to the reference image and their structure similarity
      index values were higher than 0.92 in the mouse head scan with 75% dose
      reduction. CONCLUSIONS: The authors found that in CS-based image reconstructions
      both sampling density and data incoherence affect the image quality, and suggest
      that a sampling scheme should be devised and optimized by use of these
      indicators. With this strategic approach, one can acquire optimally sampled
      sparse data so that the CS-based algorithms can best perform in terms of image
      quality.

PMID- 24320449
TI  - A full-spectral Bayesian reconstruction approach based on the material
      decomposition model applied in dual-energy computed tomography.
AB  - PURPOSE: Dual-energy computed tomography (DECT) makes it possible to get two
      fractions of basis materials without segmentation. One is the soft-tissue
      equivalent water fraction and the other is the hard-matter equivalent bone
      fraction. Practical DECT measurements are usually obtained with polychromatic x
      ray beams. Existing reconstruction approaches based on linear forward models
      without counting the beam polychromaticity fail to estimate the correct
      decomposition fractions and result in beam-hardening artifacts (BHA). The
      existing BHA correction approaches either need to refer to calibration
      measurements or suffer from the noise amplification caused by the negative-log
      preprocessing and the ill-conditioned water and bone separation problem. To
      overcome these problems, statistical DECT reconstruction approaches based on
      nonlinear forward models counting the beam polychromaticity show great potential
      for giving accurate fraction images. METHODS: This work proposes a full-spectral
      Bayesian reconstruction approach which allows the reconstruction of high quality
      fraction images from ordinary polychromatic measurements. This approach is based
      on a Gaussian noise model with unknown variance assigned directly to the
      projections without taking negative-log. Referring to Bayesian inferences, the
      decomposition fractions and observation variance are estimated by using the joint
      maximum a posteriori (MAP) estimation method. Subject to an adaptive prior model
      assigned to the variance, the joint estimation problem is then simplified into a
      single estimation problem. It transforms the joint MAP estimation problem into a
      minimization problem with a nonquadratic cost function. To solve it, the use of a
      monotone conjugate gradient algorithm with suboptimal descent steps is proposed.
      RESULTS: The performance of the proposed approach is analyzed with both simulated
      and experimental data. The results show that the proposed Bayesian approach is
      robust to noise and materials. It is also necessary to have the accurate spectrum
      information about the source-detector system. When dealing with experimental
      data, the spectrum can be predicted by a Monte Carlo simulator. For the materials
      between water and bone, less than 5% separation errors are observed on the
      estimated decomposition fractions. CONCLUSIONS: The proposed approach is a
      statistical reconstruction approach based on a nonlinear forward model counting
      the full beam polychromaticity and applied directly to the projections without
      taking negative-log. Compared to the approaches based on linear forward models
      and the BHA correction approaches, it has advantages in noise robustness and
      reconstruction accuracy.

PMID- 24320450
TI  - Patient dose simulations for scanning-beam digital x-ray tomosynthesis of the
      lungs.
AB  - PURPOSE: An improved method of image guidance for lung tumor biopsies could help
      reduce the high rate of false negatives. The aim of this work is to optimize the
      geometry of the scanning-beam digital tomography system (SBDX) for providing real
      time 3D tomographic reconstructions for target verification. The unique geometry
      of the system requires trade-offs between patient dose, imaging field of view
      (FOV), and tomographic angle. METHODS: Tomosynthetic angle as a function of tumor
      to-detector distance was calculated. Monte Carlo Software (PCXMC) was used to
      calculate organ doses and effective dose for source-to-detector distances (SDDs)
      from 90 to 150 cm, patient locations with the tumor at 20 cm from the source to
      20 cm from the detector, and FOVs centered on left lung and right lung as well as
      medial and distal peripheries of the lungs. These calculations were done for two
      systems, a SBDX system and a GE OEC-9800 C-arm fluoroscopic unit. To evaluate the
      dose effect of the system geometry, results from PCXMC were calculated using a
      scan of 300 mAs for both SBDX and fluoroscopy. The Rose Criterion was used to
      find the fluence required for a tumor SNR of 5, factoring in scatter, air-gap,
      system geometry, and patient position for all models generated with PCXMC. Using
      the calculated fluence for constant tumor SNR, the results from PCXMC were used
      to compare the patient dose for a given SNR between SBDX and fluoroscopy.
      RESULTS: Tomographic angle changes with SDD only in the region near the detector.
      Due to their geometry, the source array and detector have a peak tomographic
      angle for any given SDD at a source to tumor distance that is 69.7% of the SDD
      assuming constant source and detector size. Changing the patient location in
      order to increase tomographic angle has a significant effect on organ dose
      distribution due to geometrical considerations. With SBDX and fluoroscopy
      geometries, the dose to organs typically changes in an opposing manner with
      changing patient location. When tumor SNR is held constant (i.e., x-ray fluence
      is scaled appropriately), SBDX gives 2-10 times less dose than fluoroscopy for
      the same conditions within the typical range of patient locations. The relative
      position of the patient (as a percent of SDD) has a much more significant impact
      on dose than either SDD or patient position. The patient position providing the
      minimum dose for a given tumor SNR and SDD is approximately the same as the
      position of maximum tomographic angle. CONCLUSIONS: SBDX offers a significant
      dose advantage over currently used C-arm fluoroscopy. The patient location with
      lowest dose coincides with the location of maximum tomographic angle. In order to
      provide adequate space for the patient and for the pulmonologists' equipment, a
      SDD of 100 cm is recommended.

PMID- 24320451
TI  - Utilizing a simple CT dosimetry phantom for the comprehension of the operational
      characteristics of CT AEC systems.
AB  - PURPOSE: To investigate the utility of the nested polymethylacrylate (PMMA)
      phantom (which is available in many CT facilities for CTDI measurements), as a
      tool for the presentation and comparison of the ways that two different CT
      automatic exposure control (AEC) systems respond to a phantom when various scan
      parameters and AEC protocols are modified. METHODS: By offsetting the two
      phantom's components (the head phantom and the body ring) half-way along their
      longitudinal axis, a phantom with three sections of different x-ray attenuation
      was created. Scan projection radiographs (SPRs) and helical scans of the three
      section phantom were performed on a Toshiba Aquilion 64 and a Philips Brilliance
      64 CT scanners, with different scan parameter selections [scan direction, pitch
      factor, slice thickness, and reconstruction interval (ST/RI), AEC protocol, and
      tube potential used for the SPRs]. The dose length product (DLP) values of each
      scan were recorded and the tube current (mA) values of the reconstructed CT
      images were plotted against the respective Z-axis positions on the phantom.
      Furthermore, measurements of the noise levels at the center of each phantom
      section were performed to assess the impact of mA modulation on image quality.
      RESULTS: The mA modulation patterns of the two CT scanners were very dissimilar.
      The mA variations were more pronounced for Aquilion 64, where changes in any of
      the aforementioned scan parameters affected both the mA modulations curves and
      DLP values. However, the noise levels were affected only by changes in pitch,
      ST/RI, and AEC protocol selections. For Brilliance 64, changes in pitch affected
      the mA modulation curves but not the DLP values, whereas only AEC protocol and
      SPR tube potential selection variations affected both the mA modulation curves
      and DLP values. The noise levels increased for smaller ST/RI, larger weight
      category AEC protocol, and larger SPR tube potential selection. CONCLUSIONS: The
      nested PMMA dosimetry phantom can be effectively utilized for the comprehension
      of CT AEC systems performance and the way that different scan conditions affect
      the mA modulation patterns, DLP values, and image noise. However, in depth
      analysis of the reasons why these two systems exhibited such different behaviors
      in response to the same phantom requires further investigation which is beyond
      the scope of this study.

PMID- 24320452
TI  - Algorithmic scatter correction in dual-energy digital mammography.
AB  - PURPOSE: Small calcifications are often the earliest and the main indicator of
      breast cancer. Dual-energy digital mammography (DEDM) has been considered as a
      promising technique to improve the detectability of calcifications since it can
      be used to suppress the contrast between adipose and glandular tissues of the
      breast. X-ray scatter leads to erroneous calculations of the DEDM image. Although
      the pinhole-array interpolation method can estimate scattered radiations, it
      requires extra exposures to measure the scatter and apply the correction. The
      purpose of this work is to design an algorithmic method for scatter correction in
      DEDM without extra exposures. METHODS: In this paper, a scatter correction method
      for DEDM was developed based on the knowledge that scattered radiation has small
      spatial variation and that the majority of pixels in a mammogram are
      noncalcification pixels. The scatter fraction was estimated in the DEDM
      calculation and the measured scatter fraction was used to remove scatter from the
      image. The scatter correction method was implemented on a commercial full-field
      digital mammography system with breast tissue equivalent phantom and
      calcification phantom. The authors also implemented the pinhole-array
      interpolation scatter correction method on the system. Phantom results for both
      methods are presented and discussed. The authors compared the background DE
      calcification signals and the contrast-to-noise ratio (CNR) of calcifications in
      the three DE calcification images: image without scatter correction, image with
      scatter correction using pinhole-array interpolation method, and image with
      scatter correction using the authors' algorithmic method. RESULTS: The authors'
      results show that the resultant background DE calcification signal can be
      reduced. The root-mean-square of background DE calcification signal of 1962 MUm
      with scatter-uncorrected data was reduced to 194 MUm after scatter correction
      using the authors' algorithmic method. The range of background DE calcification
      signals using scatter-uncorrected data was reduced by 58% with scatter-corrected
      data by algorithmic method. With the scatter-correction algorithm and denoising,
      the minimum visible calcification size can be reduced from 380 to 280 MUm.
      CONCLUSIONS: When applying the proposed algorithmic scatter correction to images,
      the resultant background DE calcification signals can be reduced and the CNR of
      calcifications can be improved. This method has similar or even better
      performance than pinhole-array interpolation method in scatter correction for
      DEDM; moreover, this method is convenient and requires no extra exposure to the
      patient. Although the proposed scatter correction method is effective, it is
      validated by a 5-cm-thick phantom with calcifications and homogeneous background.
      The method should be tested on structured backgrounds to more accurately gauge
      effectiveness.

PMID- 24320453
TI  - Dose equations for tube current modulation in CT scanning and the interpretation
      of the associated CTDIvol.
AB  - PURPOSE: The scanner-reported CTDI(vol) for automatic tube current modulation
      (TCM) has a different physical meaning from the traditional CTDI(vol) at constant
      mA, resulting in the dichotomy "CTDI(vol) of the first and second kinds" for
      which a physical interpretation is sought in hopes of establishing some
      commonality between the two. METHODS: Rigorous equations are derived to describe
      the accumulated dose distributions for TCM. A comparison with formulae for
      scanner-reported CTDI(vol) clearly identifies the source of their differences.
      Graphical dose simulations are also provided for a variety of TCM tube current
      distributions (including constant mA), all having the same scanner-reported
      CTDI(vol). RESULTS: These convolution equations and simulations show that the
      local dose at z depends only weakly on the local tube current i(z) due to the
      strong influence of scatter from all other locations along z, and that the "local
      CTDI(vol)(z)" does not represent a local dose but rather only a relative i(z) =
      mA(z). TCM is a shift-variant technique to which the CTDI-paradigm does not apply
      and its application to TCM leads to a CTDI(vol) of the second kind which lacks
      relevance. CONCLUSIONS: While the traditional CTDI(vol) at constant mA conveys
      useful information (the peak dose at the center of the scan length), CTDI(vol) of
      the second kind conveys no useful information about the associated TCM dose
      distribution it purportedly represents and its physical interpretation remains
      elusive. On the other hand, the total energy absorbed E ("integral dose") as well
      as its surrogate DLP remain robust between variable i(z) TCM and constant current
      i0 techniques, both depending only on the total mAs = {i}t0 = i0t0 during the
      beam-on time t0.

PMID- 24320454
TI  - Characteristics of flattening filter free beams at low monitor unit settings.
AB  - PURPOSE: Newer linear accelerators (linacs) have been equipped to deliver
      flattening filter free (FFF) beams. When FFF beams are used for step-and-shoot
      intensity-modulated radiotherapy (IMRT), the stability of delivery of small
      numbers of monitor units (MU) is important. The authors developed automatic
      measurement techniques to evaluate the stability of the dose profile, dose
      linearity, and consistency. Here, the authors report the performance of the
      ArtisteTM accelerator (Siemens, Erlangen, Germany) in delivering low-MU FFF
      beams. METHODS: A 6 MV flattened beam (6X) with 300 MU/min dose rate and FFF
      beams of 7 (7XU) and 11 MV (11XU), each with a 500 MU/min dose rate, were
      measured at 1, 2, 3, 5, 8, 10, and 20 MU settings. For the 2000 MU/min dose rate,
      the 7 (7XUH) and 11 MV (11XUH) beams were set at 10, 15, 20, 25, and 30 MU
      because of the limits of the minimum MU settings. Beams with 20 * 20 and 10 * 10
      cm(2) field sizes were alternately measured ten times in intensity modulated (IM)
      mode, with which Siemens linacs regulate beam delivery for step-and-shoot IMRT.
      The in- and crossplane beam profiles were measured using a ProfilerTM Model 1170
      (Sun Nuclear Corporation, Melbourne, FL) in multiframe mode. The frames of 20 *
      20 cm(2) beams were identified at the off-axis profile. The 6X beam profile was
      normalized at the central axis. The 7 and 11 MV FFF beam profiles were rescaled
      to set the dose at the central axis at 145% and 170%, respectively. Point doses
      were also measured using a Farmer-type ionization chamber and water-equivalent
      solid phantom to evaluate the linearity and consistency of low-MU beam delivery.
      The values displayed on the electrometer were recognized with a USB-type camera
      and read with open-source optical character recognition software. RESULTS: The
      symmetry measurements of the 6X, 7XU, and 11XU beam profiles were better than 2%
      for beams >= 2 MU and improved with increasing MU. The variations in flatness of
      FFF beams >= 2 MU were +/- 5%. The standard deviation of the symmetry and
      flatness also decreased with increasing MU. The linearity of the 6X beam was +/-
      1% and +/- 2% for the beams of >= 5 and >= 3 MU, respectively. The 7XU and 11XU
      beams of >= 2 MU showed linearity with +/- 2% except the 7XU beam of 8 MU
      (+2.9%). The profiles of the FFF beams with 2000 and 500 MU/min dose rate were
      similar. CONCLUSIONS: The characteristics of low-MU beams delivered in IM mode
      were evaluated using an automatic measurement system developed in this study. The
      authors demonstrated that the profiles of FFF beams of the ArtisteTM linac were
      highly stable, even at low MU. The linearity of dose output was also stable for
      beams >= 2 MU.

PMID- 24320455
TI  - Development and implementation of a remote audit tool for high dose rate (HDR) Ir
      192 brachytherapy using optically stimulated luminescence dosimetry.
AB  - PURPOSE: The aim of this work was to create a mailable phantom with measurement
      accuracy suitable for Radiological Physics Center (RPC) audits of high dose-rate
      (HDR) brachytherapy sources at institutions participating in National Cancer
      Institute-funded cooperative clinical trials. Optically stimulated luminescence
      dosimeters (OSLDs) were chosen as the dosimeter to be used with the phantom.
      METHODS: The authors designed and built an 8 * 8 * 10 cm(3) prototype phantom
      that had two slots capable of holding Al2O3:C OSLDs (nanoDots; Landauer,
      Glenwood, IL) and a single channel capable of accepting all (192)Ir HDR
      brachytherapy sources in current clinical use in the United States. The authors
      irradiated the phantom with Nucletron and Varian (192)Ir HDR sources in order to
      determine correction factors for linearity with dose and the combined effects of
      irradiation energy and phantom characteristics. The phantom was then sent to
      eight institutions which volunteered to perform trial remote audits. RESULTS: The
      linearity correction factor was kL = (-9.43 * 10(-5) * dose) + 1.009, where dose
      is in cGy, which differed from that determined by the RPC for the same batch of
      dosimeters using (60)Co irradiation. Separate block correction factors were
      determined for current versions of both Nucletron and Varian (192)Ir HDR sources
      and these vendor-specific correction factors differed by almost 2.6%. For the
      Nucletron source, the correction factor was 1.026 [95% confidence interval (CI) =
      1.023-1.028], and for the Varian source, it was 1.000 (95% CI = 0.995-1.005).
      Variations in lateral source positioning up to 0.8 mm and distal/proximal source
      positioning up to 10 mm had minimal effect on dose measurement accuracy. The
      overall dose measurement uncertainty of the system was estimated to be 2.4% and
      2.5% for the Nucletron and Varian sources, respectively (95% CI). This
      uncertainty was sufficient to establish a +/- 5% acceptance criterion for source
      strength audits under a formal RPC audit program. Trial audits of four Nucletron
      sources and four Varian sources revealed an average RPC-to-institution dose ratio
      of 1.000 (standard deviation = 0.011). CONCLUSIONS: The authors have created an
      OSLD-based (192)Ir HDR brachytherapy source remote audit tool which offers
      sufficient dose measurement accuracy to allow the RPC to establish a remote audit
      program with a +/- 5% acceptance criterion. The feasibility of the system has
      been demonstrated with eight trial audits to date.

PMID- 24320456
TI  - A BrachyPhantom for verification of dose calculation of HDR brachytherapy
      planning system.
AB  - PURPOSE: To develop a calibration phantom for (192)Ir high dose rate (HDR)
      brachytherapy units that renders possible the direct measurement of absorbed dose
      to water and verification of treatment planning system. METHODS: A phantom,
      herein designated BrachyPhantom, consists of a Solid WaterTM 8-cm high cylinder
      with a diameter of 14 cm cavity in its axis that allows the positioning of an
      A1SL ionization chamber with its reference measuring point at the midheight of
      the cylinder's axis. Inside the BrachyPhantom, at a 3-cm radial distance from the
      chamber's reference measuring point, there is a circular channel connected to a
      cylindrical-guide cavity that allows the insertion of a 6-French flexible plastic
      catheter from the BrachyPhantom surface. The PENELOPE Monte Carlo code was used
      to calculate a factor, P(sw)(lw), to correct the reading of the ionization
      chamber to a full scatter condition in liquid water. The verification of dose
      calculation of a HDR brachytherapy treatment planning system was performed by
      inserting a catheter with a dummy source in the phantom channel and scanning it
      with a CT. The CT scan was then transferred to the HDR computer program in which
      a multiple treatment plan was programmed to deliver a total dose of 150 cGy to
      the ionization chamber. The instrument reading was then converted to absorbed
      dose to water using the N(gas) formalism and the P(sw)(lw) factor. Likewise, the
      absorbed dose to water was calculated using the source strength, Sk, values
      provided by 15 institutions visited in this work. RESULTS: A value of 1.020
      (0.09%, k = 2) was found for P(sw)(lw). The expanded uncertainty in the absorbed
      dose assessed with the BrachyPhantom was found to be 2.12% (k = 1). To an
      associated Sk of 27.8 cGy m(2) h(-1), the total irradiation time to deliver 150
      cGy to the ionization chamber point of reference was 161.0 s. The deviation
      between the absorbed doses to water assessed with the BrachyPhantom and those
      calculated by the treatment plans and using the Sk values did not exceed +/- 3%
      and +/- 1.6%, respectively. CONCLUSIONS: The BrachyPhantom may be conveniently
      used for quality assurance and/or verification of HDR planning system with a
      priori threshold level to spot problems of 2% and +/- 3%, respectively, and in
      the long run save time for the medical physicist.

PMID- 24320457
TI  - Fast B1 mapping based on interleaved-three-flip-angle (ITFA) excitation.
AB  - PURPOSE: Fast B1 mapping based on short-TR sequences is prone to T1-induced
      errors. The purpose of this study is to develop a novel fast B1 mapping method
      that is less prone to T1-induced errors. METHODS: The authors acquired three
      gradient echoes by applying three RF pulses of different flip angles in an
      interleaved manner. The new method, named interleaved-three-flip-angle (ITFA)
      method, employs a short TR for fast scan. Since the pixel intensity of the
      gradient echo images is dependent on both B1 and T1, the authors could compute a
      B1 map from the three gradient echo images with excluding the T1-effects. The
      authors simulated the proposed B1 mapping method for various T1 values, and they
      found optimal flip angles for ITFA experiments for a given repetition time. To
      evaluate the B1 mapping performance, the authors made a human-brain-mimicking
      phantom that had six compartments with different T1 and T2. The authors performed
      B1 mapping experiments at 3T on the phantom and a volunteer using the ITFA
      method, the actual flip angle imaging (AFI) method, and the double angle method
      (DAM), and then, the authors compared the B1 mapping results. RESULTS: Using a
      birdcage coil as a transceiver at 3T, the authors performed ITFA scans of the
      phantom and a volunteer with TR of 60 ms and the nominal flips angles of (25
      degrees , 70 degrees , 80 degrees ). The authors also performed AFI scans with
      TR1/TR2 of 30/150 ms and the nominal flip angle of 60 degrees . In both the
      phantom and human head imaging performed with the same scan times for ITFA and
      AFI, ITFA showed smaller average B1 errors than AFI when they were compared to
      DAM. CONCLUSIONS: ITFA excitations made it possible to reduce the T1-effects on
      B1 mapping of the human-brain-mimicking phantom and the human brain at 3T. The
      authors expect the ITFA method can be used for B1 shimming once the optimal flip
      angles have been predetermined for the target imaging region and for the
      preferred TR.

PMID- 24320458
TI  - Direct water and fat determination in two-point Dixon imaging with flexible echo
      times.
AB  - PURPOSE: Identifying water and fat unambiguously in multipoint Dixon imaging
      often requires phase correction, which can be challenging and may fail. The
      purpose of this work is to present a geometric interpretation of the two-point
      Dixon method with flexible echo times (TEs) and to investigate the conditions
      under which water and fat can be determined directly without phase correction.
      METHODS: Geometrically, the equation for the magnitude of the acquired signal at
      a given TE represents an ellipse in the water-fat plane centered at the origin.
      Determining water and fat in two-point Dixon imaging thus amounts to finding the
      correct intercept between two ellipses from the signals at two TEs. At the right
      TE combinations, the physicality requirement that water and fat be non-negative
      can be used to select a unique water and fat solution. Systematic computer
      simulations were conducted to examine the ranges of the TEs for which this
      approach is feasible and how different noise levels impact the feasibility.
      Phantom and in vivo experiments on a 1.5-T whole-body MRI scanner were used to
      validate the computer simulations. RESULTS: In simulation and phantom
      experiments, nearly all pixels of pure water or pure fat were reliably identified
      based on the physicality requirement alone for a range of practically useful TE
      combinations (e.g., around 3 ms/6 ms at 1.5 T) and at moderate to high SNR levels
      (>= 25). At other TE combinations, finding the correct solution based on the
      physicality requirement alone was not feasible or became sensitive to noise. In
      vivo findings were in overall agreement with the simulation and phantom studies,
      although the percentage of pixels that were correctly determined was lower.
      CONCLUSIONS: The problem of direct water and fat determination without phase
      correction can be understood geometrically. Using the physicality requirement, it
      is possible to identify the different TE combinations and imaging conditions
      under which water and fat imaging can be performed either completely without
      phase correction or by generating a first-pass solution that can be used to
      improve the processing reliability of a phase-correction based method.

PMID- 24320459
TI  - Novel magnetomechanical MR compatible vibrational device for producing
      kinesthetic illusion during fMRI.
AB  - PURPOSE: Functional MRI (fMRI) can provide insights into the functioning of the
      sensorimotor system, which is of particular interest in studying people with
      movement disorders or chronic pain conditions. This creates a demand for
      manipulanda that can fit and operate within the environment of a MRI scanner.
      Here, the authors present a magnetomechanical device that delivers a vibrotactile
      sensation to the skin with a force of approximately 9 N. METHODS: MRI
      compatibility of the device was tested in a 3 T scanner using a phantom to
      simulate the head. Preliminary investigation into the effectiveness of the device
      at producing cortical and subcortical activity was also conducted with a group of
      seven healthy subjects. The vibration was applied to the right extensor carpi
      ulnaris tendon to induce a kinesthetic illusion of flexion and extension of the
      wrist. RESULTS: The MRI compatibility tests showed the device did not produce
      image artifacts and the generated electromagnetic field did not disrupt the
      static magnetic field of the scanner or its operation. The subject group results
      showed activity in the contralateral putamen, premotor cortex, and dorsal lateral
      prefrontal cortex. Ipsilaterally, there was increased activity in the superior
      and inferior parietal lobules. Areas that activated bilaterally included the
      thalamus, anterior cingulate, secondary somatosensory areas (S2), temporal lobes,
      and visual association areas. CONCLUSIONS: This device offers an effective tool
      with precise control over the vibratory stimulus, delivering higher forces than
      some other types of devices (e.g., piezoelectric actuators). It can be useful for
      investigating sensory systems and sensorimotor integration.

PMID- 24320460
TI  - Design and performance of a compact and stationary microSPECT system.
AB  - PURPOSE: Over the last ten years, there has been an extensive growth in the
      development of microSPECT imagers. Most of the systems are based on the
      combination of conventional, relatively large gamma cameras with poor intrinsic
      spatial resolution and multipinhole collimators working in large magnification
      mode. Spatial resolutions range from 0.58 to 0.76 mm while peak sensitivities
      vary from 0.06% to 0.4%. While pushing the limits of performance is of major
      importance, the authors believe that there is a need for smaller and less complex
      systems that bring along a reduced cost. While low footprint and low-cost systems
      can make microSPECT available to more researchers, the ease of operation and
      calibration and low maintenance cost are additional factors that can facilitate
      the use of microSPECT in molecular imaging. In this paper, the authors simulate
      the performance of a microSPECT imager that combines high space-bandwidth
      detectors and pinholes with truncated projection, resulting in a small and
      stationary system. METHODS: A system optimization algorithm is used to determine
      the optimal SPECT systems, given our high resolutions detectors and a fixed field
      of-view. These optimal system geometries are then used to simulate a Defrise disk
      phantom and a hot rod phantom. Finally, a MOBY mouse phantom, with realistic
      concentrations of Tc99m-tetrofosmin is simulated. RESULTS: Results show that the
      authors can successfully reconstruct a Defrise disk phantom of 24 mm in diameter
      without any rotating system components or translation of the object.
      Reconstructed spatial resolution is approximately 800 MUm while the peak
      sensitivity is 0.23%. Finally, the simulation of the MOBY mouse phantom shows
      that the authors can accurately reconstruct mouse images. CONCLUSIONS: These
      results show that pinholes with truncated projections can be used in small
      magnification or minification mode to obtain a compact and stationary microSPECT
      system. The authors showed that they can reach state-of-the-art system
      performance and can successfully reconstruct images with realistic noise levels
      in a preclinical context. Such a system can be useful for dynamic SPECT imaging.

PMID- 24320461
TI  - Quantitative Monte Carlo-based holmium-166 SPECT reconstruction.
AB  - PURPOSE: Quantitative imaging of the radionuclide distribution is of increasing
      interest for microsphere radioembolization (RE) of liver malignancies, to aid
      treatment planning and dosimetry. For this purpose, holmium-166 ((166)Ho)
      microspheres have been developed, which can be visualized with a gamma camera.
      The objective of this work is to develop and evaluate a new reconstruction method
      for quantitative (166)Ho SPECT, including Monte Carlo-based modeling of photon
      contributions from the full energy spectrum. METHODS: A fast Monte Carlo (MC)
      simulator was developed for simulation of (166)Ho projection images and
      incorporated in a statistical reconstruction algorithm (SPECT-fMC). Photon
      scatter and attenuation for all photons sampled from the full (166)Ho energy
      spectrum were modeled during reconstruction by Monte Carlo simulations. The
      energy- and distance-dependent collimator-detector response was modeled using
      precalculated convolution kernels. Phantom experiments were performed to
      quantitatively evaluate image contrast, image noise, count errors, and activity
      recovery coefficients (ARCs) of SPECT-fMC in comparison with those of an energy
      window-based method for correction of down-scattered high-energy photons (SPECT
      DSW) and a previously presented hybrid method that combines MC simulation of
      photopeak scatter with energy window-based estimation of down-scattered high
      energy contributions (SPECT-ppMC+DSW). Additionally, the impact of SPECT-fMC on
      whole-body recovered activities (A(est)) and estimated radiation absorbed doses
      was evaluated using clinical SPECT data of six (166)Ho RE patients. RESULTS: At
      the same noise level, SPECT-fMC images showed substantially higher contrast than
      SPECT-DSW and SPECT-ppMC+DSW in spheres >= 17 mm in diameter. The count error was
      reduced from 29% (SPECT-DSW) and 25% (SPECT-ppMC+DSW) to 12% (SPECT-fMC). ARCs in
      five spherical volumes of 1.96-106.21 ml were improved from 32%-63% (SPECT-DSW)
      and 50%-80% (SPECT-ppMC+DSW) to 76%-103% (SPECT-fMC). Furthermore, SPECT-fMC
      recovered whole-body activities were most accurate (A(est) = 1.06 * A - 5.90 MBq,
      R(2) = 0.97) and SPECT-fMC tumor absorbed doses were significantly higher than
      with SPECT-DSW (p = 0.031) and SPECT-ppMC+DSW (p = 0.031). CONCLUSIONS: The
      quantitative accuracy of (166)Ho SPECT is improved by Monte Carlo-based modeling
      of the image degrading factors. Consequently, the proposed reconstruction method
      enables accurate estimation of the radiation absorbed dose in clinical practice.

PMID- 24320462
TI  - An automated voxelized dosimetry tool for radionuclide therapy based on serial
      quantitative SPECT/CT imaging.
AB  - PURPOSE: To create an accurate map of the distribution of radiation dose
      deposition in healthy and target tissues during radionuclide therapy. METHODS:
      Serial quantitative SPECT/CT images were acquired at 4, 24, and 72 h for 28
      (177)Lu-octreotate peptide receptor radionuclide therapy (PRRT) administrations
      in 17 patients with advanced neuroendocrine tumors. Deformable image registration
      was combined with an in-house programming algorithm to interpolate
      pharmacokinetic uptake and clearance at a voxel level. The resultant cumulated
      activity image series are comprised of values representing the total number of
      decays within each voxel's volume. For PRRT, cumulated activity was translated to
      absorbed dose based on Monte Carlo-determined voxel S-values at a combination of
      long and short ranges. These dosimetric image sets were compared for mean
      radiation absorbed dose to at-risk organs using a conventional MIRD protocol
      (OLINDA 1.1). RESULTS: Absorbed dose values to solid organs (liver, kidneys, and
      spleen) were within 10% using both techniques. Dose estimates to marrow were
      greater using the voxelized protocol, attributed to the software incorporating
      crossfire effect from nearby tumor volumes. CONCLUSIONS: The technique presented
      offers an efficient, automated tool for PRRT dosimetry based on serial post
      therapy imaging. Following retrospective analysis, this method of high-resolution
      dosimetry may allow physicians to prescribe activity based on required dose to
      tumor volume or radiation limits to healthy tissue in individual patients.

PMID- 24320464
TI  - Effect of 176Lu intrinsic radioactivity on dual head PET system imaging and data
      acquisition, simulation, and experimental measurements.
AB  - PURPOSE: In this work, the authors aim for the estimation of the effect of
      (176)Lu intrinsic radioactivity on the performance of a dual head PET system
      dedicated to small animal imaging. METHODS: A prototype camera has been used as a
      reference system in order to validate two GATE simulation models, which were used
      for the investigation. The first model includes the (176)Lu intrinsic
      radioactivity, while the second does not. The two models have been designed in
      order to provide similar sensitivities, in terms of count rate performance and
      scatter fraction, in the linear range of activities. In addition, the model with
      the (176)Lu intrinsic radioactivity, has been validated in terms of background
      count rate. Different acquisition schemes have been examined in order to
      determine the optimum conditions to minimize the (176)Lu effects, while
      maintaining a high trues count rate. In addition, the effect on the image
      quality, in terms of spatial resolution, signal-to-noise ratio, and minimum
      detectable activity, was investigated. RESULTS: Both models are in good agreement
      with the measured data. While, the presence of the (176)Lu altered the dead time
      of the model, it also affected the singles, trues, and randoms count rates. The
      noise equivalent count rate curves of the two models indicate that for low
      activities, the lack of (176)Lu radioactivity leads to better noise properties
      due to the underestimation of the randoms. Signal-to-noise ratio measurement on
      coincidence images confirm the aforementioned claim, since the model without the
      (176)Lu provides better less noisy images. Furthermore, the spatial resolution
      and the minimum detectable activity are overestimated. CONCLUSIONS: It has been
      proven that the lack of the (176)Lu intrinsic radioactivity has an impact on the
      design of the simulation model's dead time. Even if there is an alignment with
      experimental results still the noise properties, for a wide range of activities,
      are overestimated. In addition, for low activities, better image quality, is
      presented, mainly due to the lack of the (176)Lu photons which blur the images.
      Furthermore, it was shown that the use of a high hardware threshold allows the
      application of a wide energy window, which improves the statistics without a
      significant compromise on the quality of the detected photons, mainly, due to the
      early rejection of the low energy photons and the low scatter factor.

PMID- 24320463
TI  - Use of MRI to assess the prediction of heart motion with gross body motion in
      myocardial perfusion imaging by stereotracking of markers on the body surface.
AB  - PURPOSE: The aim of this study is to determine using MRI in volunteers whether
      the rigid-body-motion (RBM) model can be approximately used to estimate the gross
      body-motion of the heart from that of external markers on patient's chest. Our
      target clinical application is to use a visual-tracking-system (VTS) which
      employs stereoimaging to estimate heart motion during SPECT/CT and PET/CT
      myocardial perfusion imaging. METHODS: To investigate body-motion separate from
      the respiration the authors had the volunteers hold their breath during the
      acquisition of a sequence of two sets of EKG-triggered MRI sagittal slices. The
      first set was acquired pre-motion, and the second postmotion. The motion of the
      heart within each breath-hold set of slices was estimated by registration to the
      semiautomatic 3D segmentation of the heart region in a baseline set acquired
      using the Navigator technique. The motion of the heart between the pre- and
      postmotion sets was then determined as the difference in the individual motions
      in comparison to the Navigator sets. An analysis of the combined motion of the
      individual markers on the chest was used to obtain an estimate of the six-degree
      of-freedom RBM from the VTS system. The metric for judging agreement between the
      motion estimated by MRI and the VTS was the average error. This was defined as
      the average of the magnitudes of the differences in the vector displacements of
      all voxels in the heart region. Studies with the Data Spectrum Anthropomorphic
      Phantom and "No-Motion" studies in which the volunteer did not intentionally move
      were used to establish a baseline for agreement. With volunteer studies a t-test
      was employed to determine when statistically significant differences in Average
      Errors occurred compared to the No-motion studies. RESULTS: For phantom
      acquisitions, the Average Error when the motion was just translation was 0.1 mm.
      With complex motions, which included a combination of rotations and translations,
      the Average Error increased to 3.6 mm. In the volunteers the Average Error
      averaged over all No-Motion acquisitions was 1.0 mm. For the case of
      translational motion, which might be expected to be RBM, the Average Error
      averaged over all volunteer studies increased to 2.6 mm, which was statistically
      different from the No-Motion studies. For the case of bends and twists of the
      torso, which would be expected to challenge the RBM model, the Average Error
      averaged over all such volunteer studies was 4.9 mm and was again statistically
      different. Investigations of motion of the arm including just bending at the
      elbow and leg motion resulted in Average Errors which were not statistically
      different from the No-Motion studies. However, when shoulder movement was
      included with arm motion the Average Error was near that of torso bends and
      twists, and statistically different. CONCLUSIONS: Use of the RBM model with VTS
      predictions of heart motion during reconstruction should decrease the extent of
      artifacts for the types of patient motion studied. The impact of correction would
      be less for torso bends and twists, and arm motion which includes the shoulders.

PMID- 24320465
TI  - Investigation of realistic PET simulations incorporating tumor patient's
      specificity using anthropomorphic models: creation of an oncology database.
AB  - PURPOSE: The GATE Monte Carlo simulation toolkit is used for the implementation
      of realistic PET simulations incorporating tumor heterogeneous activity
      distributions. The reconstructed patient images include noise from the
      acquisition process, imaging system's performance restrictions and have limited
      spatial resolution. For those reasons, the measured intensity cannot be simply
      introduced in GATE simulations, to reproduce clinical data. Investigation of the
      heterogeneity distribution within tumors applying partial volume correction (PVC)
      algorithms was assessed. The purpose of the present study was to create a
      simulated oncology database based on clinical data with realistic intratumor
      uptake heterogeneity properties. METHODS: PET/CT data of seven oncology patients
      were used in order to create a realistic tumor database investigating the
      heterogeneity activity distribution of the simulated tumors. The anthropomorphic
      models (NURBS based cardiac torso and Zubal phantoms) were adapted to the CT data
      of each patient, and the activity distribution was extracted from the respective
      PET data. The patient-specific models were simulated with the Monte Carlo Geant4
      application for tomography emission (GATE) in three different levels for each
      case: (a) using homogeneous activity within the tumor, (b) using heterogeneous
      activity distribution in every voxel within the tumor as it was extracted from
      the PET image, and (c) using heterogeneous activity distribution corresponding to
      the clinical image following PVC. The three different types of simulated data in
      each case were reconstructed with two iterations and filtered with a 3D Gaussian
      postfilter, in order to simulate the intratumor heterogeneous uptake.
      Heterogeneity in all generated images was quantified using textural feature
      derived parameters in 3D according to the ground truth of the simulation, and
      compared to clinical measurements. Finally, profiles were plotted in central
      slices of the tumors, across lines with heterogeneous activity distribution for
      visual assessment. RESULTS: The accuracy of the simulated database was assessed
      against the original clinical images. The PVC simulated images matched the
      clinical ones best. Local, regional, and global features extracted from the PVC
      simulated images were closest to the clinical measurements, with the exception of
      the size zone variability and the mean intensity values, where heterogeneous
      tumors showed better reproducibility. The profiles on PVC simulated tumors after
      postfiltering seemed to represent the more realistic heterogeneous regions with
      respect to the clinical reference. CONCLUSIONS: In this study, the authors
      investigated the input activity map heterogeneity in the GATE simulations of
      tumors with heterogeneous activity distribution. The most realistic heterogeneous
      tumors were obtained by inserting PVC activity distributions from the clinical
      image into the activity map of the simulation. Partial volume effect (PVE) can
      play a crucial role in the quantification of heterogeneity within tumors and have
      an important impact on applications such as patient follow-up during treatment
      and assessment of tumor response to therapy. The development of such a database
      incorporating patient anatomical and functional variability can be used to
      evaluate new image processing or analysis algorithms, while providing control of
      the ground truth, which is not available when dealing with clinical datasets. The
      database includes all images used and generated in this study, as well as the
      sinograms and the attenuation phantoms for further investigation. It is freely
      available to the interested reader of the journal at
      http://www.med.upatras.gr/oncobase/.

PMID- 24320466
TI  - Event-by-event respiratory motion correction for PET with 3D internal-1D external
      motion correlation.
AB  - PURPOSE: Respiratory motion during PET/CT imaging can cause substantial image
      blurring and underestimation of tracer concentration for both static and dynamic
      studies. In this study, the authors developed an event-by-event respiratory
      motion correction method that used three-dimensional internal-one-dimensional
      external motion correlation (INTEX3D) in listmode reconstruction. The authors aim
      to fully correct for organ/tumor-specific rigid motion caused by respiration
      using all detected events to eliminate both intraframe and interframe motion, and
      investigate the quantitative improvement in static and dynamic imaging. METHODS:
      The positional translation of an internal organ or tumor during respiration was
      first determined from the reconstructions of multiple phase-gated images. A level
      set (active contour) method was used to segment the targeted internal
      organs/tumors whose centroids were determined. The mean displacement of the
      external respiratory signal acquired by the Anzai system that corresponded to
      each phase-gated frame was determined. Three linear correlations between the 1D
      Anzai mean displacements and the 3D centroids of the internal organ/tumor were
      established. The 3D internal motion signal with high temporal resolution was then
      generated by applying each of the three correlation functions to the entire Anzai
      trace (40 Hz) to guide event-by-event motion correction in listmode
      reconstruction. The reference location was determined as the location where CT
      images were acquired to facilitate phase-matched attenuation correction and
      anatomical-based postfiltering. The proposed method was evaluated with a NEMA
      phantom driven by a QUASAR respiratory motion platform, and human studies with
      two tracers: pancreatic beta cell tracer [(18)F]FP(+)DTBZ and tumor hypoxia
      tracer [(18)F]fluoromisonidazole (FMISO). An anatomical-based postreconstruction
      filter was applied to the motion-corrected images to reduce noise while
      preserving quantitative accuracy and organ boundaries in the patient studies.
      RESULTS: The INTEX3D method yielded an increase of 5%-9% and 32%-40% in contrast
      recovery coefficient on the hot spheres in the NEMA phantom, compared to the
      reconstructions with only 1D motion correction (INTEX1D) and no motion
      correction, respectively. The proposed method also increased the mean activities
      of the pancreas and kidney by 9.3% and 11.2%, respectively, across three subjects
      in the FPDTBZ studies, and the average lesion-to-blood ratio by 20% across three
      lesions in the FMISO study, compared to the reconstructions without motion
      correction. In addition, the proposed method reduced intragate motion as compared
      to phase-gated images. The application of the anatomical-based postreconstruction
      filter further reduced noise in the background by >50% compared to
      reconstructions without postfiltering, while preserving quantitative accuracy and
      organ boundaries. Finally, the measurements of the time-activity curves from a
      subject with FPDTBZ showed that INTEX3D yielded 18% and 11% maximum increases in
      tracer concentration in the pancreas and kidney cortex, respectively.
      CONCLUSIONS: These results suggest that the proposed method can effectively
      compensate for both intragate and intergate respiratory motion while preserving
      all the counts, and is applicable to dynamic studies.

PMID- 24320467
TI  - Thermochromic phase-transitions of GafChromic films studied by z-scan and
      temperature-dependent absorbance measurements.
AB  - PURPOSE: Upon irradiation the active diacetylene layer of radiochromic films
      undergoes dose-dependent polymerization in the blue polydiacetylene form. Dose
      assessment is currently based on linear absorbance measurements. The scope of the
      present study was designed for the further understanding of the linear and, in
      particular, the nonlinear optical characteristics of such films and the
      utilization of these characteristics for devising alternative "reading"
      procedures. METHODS: The nonlinear optical interactions of laser light with
      previously irradiated GafChromic((r)) HD-810 and MD55-2 films were studied by z
      scan techniques. The focused laser beam strikes on the film, which is located at
      various distances from the focal spot. The beam induces linear and nonlinear
      absorption and refraction. The measurement of the transmitted power (open
      aperture z-scan) allows the study of the nonlinear absorption. On the other hand,
      the measurement of the axial region of the transmitted beam (closed-aperture z
      scan) is related to both nonlinear absorption and refraction effects. A 10 mW,
      633 nm, linearly polarized He/Ne laser was employed as the light source. The
      transmittance measurements were coupled with absorbance measurements carried out
      over the whole visible spectrum and at various reading temperatures, in an
      attempt to clarify the underlying mechanisms dictating the observed effects.
      These effects were incorporated to an open-aperture z-scan model, developed for
      the purpose of comparison to the corresponding experimental curves. RESULTS: The
      transmittance data obtained by both open- and closed-aperture z-scan were found
      to be dose-dependent, thus allowing such transmittance techniques to be employed
      for dose assessment. Low power open-aperture z-scan measurements (sensitive to
      absorptive nonlinearities) revealed a stepwise two-photon excitation of the
      active layer, through an intermediate state. At higher laser intensities (and/or
      absorbed dose), the shapes of the z-scan curves were found to be more
      complicated. These shapes were attributed to a temperature-dependent
      (thermochromic) transition from the blue form to the conformer red form of the
      active material, a transition which appears to be irreversible at high
      intensities. This transition was incorporated into the open-aperture z-scan model
      which reproduced satisfactorily the corresponding experimental curves. Finally,
      the use of a chopped laser beam in the closed-aperture z-scan technique allowed
      artifact-free, high spatial resolution dose measurements using a laser beam of
      relatively high power. CONCLUSIONS: The model developed in the present study
      elucidates some of the effects related to film reading and the causes of some of
      the artifacts reported in the literature. Two-dimensional dose distributions can
      be assessed by z-scan; however, the merits of such a technique relative to those
      currently in use have to be further investigated.

PMID- 24320469
TI  - Automatic localization of the fetal cerebellum on 3D ultrasound volumes.
AB  - PURPOSE: Assessment of the fetal cerebellar volume on 3D ultrasound data sets is
      very important in the clinical evaluation of the fetal growth and health.
      However, the irregular shape of the cerebellum and the strong artifacts of
      ultrasound images complicate the segmentation without manual intervention. In
      this paper, the authors propose an approach to locate the cerebellum
      automatically, which is considered as a prework of the segmentation. METHODS: The
      authors present a weighted Hough transform and a constrained randomized Hough
      transform to detect the fetal brain midline and the skull, respectively. By
      combining the location information of these two structures with local image
      features, a constrained probabilistic boosting tree is then proposed to search
      the cerebellum. RESULTS: This algorithm was tested on ultrasound volumes of the
      fetal head with the gestational age ranging from 20 to 33 weeks. Compared with
      manual measurements, this algorithm obtained a satisfactory performance with the
      mean Dice similarity coefficient of 0.92 and the average processing time of 0.75
      s per case. CONCLUSIONS: The results demonstrate that the proposed method is an
      automatic, fast, and accurate tool for searching the fetal cerebellum on
      ultrasound volumes.

PMID- 24320468
TI  - Integrated ultrasound and magnetic resonance imaging for simultaneous temperature
      and cavitation monitoring during focused ultrasound therapies.
AB  - PURPOSE: Ultrasound can be used to noninvasively produce different bioeffects via
      viscous heating, acoustic cavitation, or their combination, and these effects can
      be exploited to develop a wide range of therapies for cancer and other disorders.
      In order to accurately localize and control these different effects, imaging
      methods are desired that can map both temperature changes and cavitation
      activity. To address these needs, the authors integrated an ultrasound imaging
      array into an MRI-guided focused ultrasound (MRgFUS) system to simultaneously
      visualize thermal and mechanical effects via passive acoustic mapping (PAM) and
      MR temperature imaging (MRTI), respectively. METHODS: The system was tested with
      an MRgFUS system developed for transcranial sonication for brain tumor ablation
      in experiments with a tissue mimicking phantom and a phantom-filled ex vivo
      macaque skull. In experiments on cavitation-enhanced heating, 10 s continuous
      wave sonications were applied at increasing power levels (30-110 W) until
      broadband acoustic emissions (a signature for inertial cavitation) were evident.
      The presence or lack of signal in the PAM, as well as its magnitude and location,
      were compared to the focal heating in the MRTI. Additional experiments compared
      PAM with standard B-mode ultrasound imaging and tested the feasibility of the
      system to map cavitation activity produced during low-power (5 W) burst
      sonications in a channel filled with a microbubble ultrasound contrast agent.
      RESULTS: When inertial cavitation was evident, localized activity was present in
      PAM and a marked increase in heating was observed in MRTI. The location of the
      cavitation activity and heating agreed on average after registration of the two
      imaging modalities; the distance between the maximum cavitation activity and
      focal heating was -3.4 +/- 2.1 mm and -0.1 +/- 3.3 mm in the axial and transverse
      ultrasound array directions, respectively. Distortions and other MRI issues
      introduced small uncertainties in the PAM/MRTI registration. Although there was
      substantial variation, a nonlinear relationship between the average intensity of
      the cavitation maps, which was relatively constant during sonication, and the
      peak temperature rise was evident. A fit to the data to an exponential had a
      correlation coefficient (R(2)) of 0.62. The system was also found to be capable
      of visualizing cavitation activity with B-mode imaging and of passively mapping
      cavitation activity transcranially during cavitation-enhanced heating and during
      low-power sonication with an ultrasound contrast agent. CONCLUSIONS: The authors
      have demonstrated the feasibility of integrating an ultrasound imaging array into
      an MRgFUS system to simultaneously map localized cavitation activity and
      temperature. The authors anticipate that this integrated approach can be utilized
      to develop controllers for cavitation-enhanced ablation and facilitate the
      optimization and development of this and other ultrasound therapies. The
      integrated system may also provide a useful tool to study the bioeffects of
      acoustic cavitation.

PMID- 24320470
TI  - A 3D ultrasound scanning system for image guided liver interventions.
AB  - PURPOSE: Two-dimensional ultrasound (2D US) imaging is commonly used for
      diagnostic and intraoperative guidance of interventional liver procedures;
      however, 2D US lacks volumetric information that may benefit interventional
      procedures. Over the past decade, three-dimensional ultrasound (3D US) has been
      developed to provide the missing spatial information. 3D US image acquisition is
      mainly based on mechanical, electromagnetic, and freehand tracking of
      conventional 2D US transducers, or 2D array transducers available on high-end
      machines. These approaches share many problems during clinical use for
      interventional liver imaging due to lack of flexibility and compatibility with
      interventional equipment, limited field-of-view (FOV), and significant capital
      cost compared to the benefits they introduce. In this paper, a novel system for
      mechanical 3D US scanning is introduced to address these issues. METHODS: The
      authors have developed a handheld mechanical 3D US system that incorporates
      mechanical translation and tilt sector sweeping of any standard 2D US transducer
      to acquire 3D images. Each mechanical scanning function can be operated
      independently or may be combined to allow for a hybrid wide FOV acquisition. The
      hybrid motion mode facilitates registration of other modalities (e.g., CT or MRI)
      to the intraoperative 3D US images by providing a larger FOV in which to acquire
      anatomical information. The tilting mechanism of the developed mover allows image
      acquisition in the intercostal rib space to avoid acoustic shadowing from bone.
      The geometric and volumetric scanning validity of the 3D US system was evaluated
      on tissue mimicking US phantoms for different modes of operation. Identical
      experiments were performed on a commercially available 3D US system for direct
      comparison. To replicate a clinical scenario, the authors evaluated their 3D US
      system by comparing it to CT for measurement of angle and distance between
      interventional needles in different configurations, similar to those used for
      percutaneous ablation of liver tumors. RESULTS: The mean geometrical hybrid 3D
      reconstruction error measured from scanning of a known string phantom was less
      than 1 mm in two directions and 2.5 mm in the scanning direction, which was
      comparable or better than the same measurements obtained from a commercially
      available 3D US system. The error in volume measurements of spherical phantom
      models depended on depth of the object. For a 20 cm(3) model at a depth of 15 cm,
      a standard depth for liver imaging, the mean error was 3.6% +/- 4.5% comparable
      to the 2.3% +/- 1.8% error for the 3D US commercial system. The error in 3D US
      measurement of the tip distance and angle between two microwave ablation antennas
      inserted into the phantom was 0.9 +/- 0.5 mm and 1.1 degrees  +/- 0.7 degrees ,
      respectively. CONCLUSIONS: A 3D US system with hybrid scanning motions for large
      field-of-view 3D abdominal imaging has been developed and validated. The superior
      spatial information provided by 3D US might enhance image-guidance for
      percutaneous interventional treatment of liver malignancies. The system has
      potential to be integrated with other liver procedures and has application in
      other abdominal organs such as kidneys, spleen, or adrenals.

PMID- 24320471
TI  - Dedicated 3D photoacoustic breast imaging.
AB  - PURPOSE: To report the design and imaging methodology of a photoacoustic scanner
      dedicated to imaging hemoglobin distribution throughout a human breast. METHODS:
      The authors developed a dedicated breast photoacoustic mammography (PAM) system
      using a spherical detector aperture based on our previous photoacoustic
      tomography scanner. The system uses 512 detectors with rectilinear scanning. The
      scan shape is a spiral pattern whose radius varies from 24 to 96 mm, thereby
      allowing a field of view that accommodates a wide range of breast sizes. The
      authors measured the contrast-to-noise ratio (CNR) using a target comprised of 1
      mm dots printed on clear plastic. Each dot absorption coefficient was
      approximately the same as a 1-mm thickness of whole blood at 756 nm, the output
      wavelength of the Alexandrite laser used by this imaging system. The target was
      immersed in varying depths of an 8% solution of stock Liposyn II-20%, which
      mimics the attenuation of breast tissue (1.1 cm(-1)). The spatial resolution was
      measured using a 6 MUm-diameter carbon fiber embedded in agar. The breasts of
      four healthy female volunteers, spanning a range of breast size from a brassiere
      C cup to a DD cup, were imaged using a 96-mm spiral protocol. RESULTS: The CNR
      target was clearly visualized to a depth of 53 mm. Spatial resolution, which was
      estimated from the full width at half-maximum of a profile across the PAM image
      of a carbon fiber, was 0.42 mm. In the four human volunteers, the vasculature was
      well visualized throughout the breast tissue, including to the chest wall.
      CONCLUSIONS: CNR, lateral field-of-view and penetration depth of our dedicated
      PAM scanning system is sufficient to image breasts as large as 1335 mL, which
      should accommodate up to 90% of the women in the United States.

PMID- 24320472
TI  - Blood vessel-based liver segmentation using the portal phase of an abdominal CT
      dataset.
AB  - PURPOSE: Blood vessel (BV) information can be used to guide body organ
      segmentation on computed tomography (CT) imaging. The proposed method uses
      abdominal BVs (ABVs) to segment the liver through the portal phase of an
      abdominal CT dataset. This method aims to address the wide variability in liver
      shape and size, separate liver from other organs of similar intensity, and
      segment hepatic low-intensity tumors (LITs). METHODS: Thin ABVs are enhanced
      using three-dimensional (3D) opening. ABVs are extracted and classified into
      hepatic BVs (HBVs) and nonhepatic BVs (non-HBVs) with a small number of
      interactions, and HBVs and non-HBVs are used for constraining automatic liver
      segmentation. HBVs are used to individually segment the core region of the liver.
      To separate the liver from other organs, this core region and non-HBVs are used
      to construct an initial 3D boundary surface. To segment LITs, the core region is
      classified into non-LIT- and LIT-parts by fitting the histogram of the core
      region using a variational Bayesian Gaussian mixture model. Each part of the core
      region is extended based on its corresponding component of the mixture, and
      extension is completed when it reaches a variation in intensity or the
      constructed boundary surface, which is reconfirmed to fit robustly between the
      liver and neighboring organs of similar intensity. A solid-angle technique is
      used to refine main BVs at the entrances to the inferior vena cava and the portal
      vein. RESULTS: The proposed method was applied to 80 datasets: 30 Medical Image
      Computing and Computer Assisted Intervention (MICCAI) and 50 non-MICCAI; 30
      datasets of non-MICCAI data include tumors. Our results for MICCAI-test data were
      evaluated by sliver07 (http://www.sliver07.org/) organizers with an overall score
      of 85.7, which ranks best on the site as of July 2013. These results (average +/-
      standard deviation) include the five error measures of the 2007 MICCAI workshop
      for liver segmentation as follows. Results for volume overlap error, relative
      volume difference, average symmetric surface distance, root mean square symmetric
      surface distance, and maximum symmetric surface distance were 4.33 +/- 0.73, 0.28
      +/- 0.87, 0.63 +/- 0.16, 1.19 +/- 0.28, and 14.01 +/- 2.88, respectively; and
      when applying our method to non-MICCAI data, results were 3.21 +/- 0.75, 0.06 +/-
      1.29, 0.45 +/- 0.17, 0.98 +/- 0.26, and 12.69 +/- 3.89, respectively. These
      results demonstrate high performance of the method when applied to different CT
      datasets. CONCLUSIONS: BVs can be used to address the wide variability in liver
      shape and size, as BVs provide unique details for the structure of each studied
      liver. Constructing a boundary surface using HBVs and non-HBVs can separate liver
      from its neighboring organs of similar intensity. By fitting the histogram of the
      core region using a variational Bayesian Gaussian mixture model, LITs are
      segmented and measuring the volumetry of non-LIT- and LIT-parts becomes possible.
      Further examination of the proposed method on a large number of datasets is
      required for clinical applications, and development of the method for full
      automation may be possible and useful in the clinic.

PMID- 24320473
TI  - Breast Imaging Reporting and Data System (BI-RADS) breast composition
      descriptors: automated measurement development for full field digital
      mammography.
AB  - PURPOSE: The Breast Imaging Reporting and Data System (BI-RADS) breast
      composition descriptors are used for standardized mammographic reporting and are
      assessed visually. This reporting is clinically relevant because breast
      composition can impact mammographic sensitivity and is a breast cancer risk
      factor. New techniques are presented and evaluated for generating automated BI
      RADS breast composition descriptors using both raw and calibrated full field
      digital mammography (FFDM) image data. METHODS: A matched case-control dataset
      with FFDM images was used to develop three automated measures for the BI-RADS
      breast composition descriptors. Histograms of each calibrated mammogram in the
      percent glandular (pg) representation were processed to create the new BR(pg)
      measure. Two previously validated measures of breast density derived from
      calibrated and raw mammograms were converted to the new BR(vc) and BR(vr)
      measures, respectively. These three measures were compared with the radiologist
      reported BI-RADS compositions assessments from the patient records. The authors
      used two optimization strategies with differential evolution to create these
      measures: method-1 used breast cancer status; and method-2 matched the reported
      BI-RADS descriptors. Weighted kappa (kappa) analysis was used to assess the
      agreement between the new measures and the reported measures. Each measure's
      association with breast cancer was evaluated with odds ratios (ORs) adjusted for
      body mass index, breast area, and menopausal status. ORs were estimated as per
      unit increase with 95% confidence intervals. RESULTS: The three BI-RADS measures
      generated by method-1 had kappa between 0.25-0.34. These measures were
      significantly associated with breast cancer status in the adjusted models: (a) OR
      = 1.87 (1.34, 2.59) for BR(pg); (b) OR = 1.93 (1.36, 2.74) for BR(vc); and (c) OR
      = 1.37 (1.05, 1.80) for BR(vr). The measures generated by method-2 had kappa
      between 0.42-0.45. Two of these measures were significantly associated with
      breast cancer status in the adjusted models: (a) OR = 1.95 (1.24, 3.09) for
      BR(pg); (b) OR = 1.42 (0.87, 2.32) for BR(vc); and (c) OR = 2.13 (1.22, 3.72) for
      BR(vr). The radiologist-reported measures from the patient records showed a
      similar association, OR = 1.49 (0.99, 2.24), although only borderline
      statistically significant. CONCLUSIONS: A general framework was developed and
      validated for converting calibrated mammograms and continuous measures of breast
      density to fully automated approximations for the BI-RADS breast composition
      descriptors. The techniques are general and suitable for a broad range of
      clinical and research applications.

PMID- 24320474
TI  - Separate modal analysis for tumor detection with a digital image elasto
      tomography (DIET) breast cancer screening system.
AB  - PURPOSE: It is estimated that every year, 1 * 10(6) women are diagnosed with
      breast cancer, and more than 410,000 die annually worldwide. Digital Image Elasto
      Tomography (DIET) is a new noninvasive breast cancer screening modality that
      induces mechanical vibrations in the breast and images its surface motion with
      digital cameras to detect changes in stiffness. This research develops a new
      automated approach for diagnosing breast cancer using DIET based on a modal
      analysis model. METHODS: The first and second natural frequency of silicone
      phantom breasts is analyzed. Separate modal analysis is performed for each region
      of the phantom to estimate the modal parameters using imaged motion data over
      several input frequencies. Statistical methods are used to assess the likelihood
      of a frequency shift, which can indicate tumor location. Phantoms with 5, 10, and
      20 mm stiff inclusions are tested, as well as a homogeneous (healthy) phantom.
      Inclusions are located at four locations with different depth. RESULTS: The
      second natural frequency proves to be a reliable metric with the potential to
      clearly distinguish lesion like inclusions of different stiffness, as well as
      providing an approximate location for the tumor like inclusions. The 10 and 20 mm
      inclusions are always detected regardless of depth. The 5 mm inclusions are only
      detected near the surface. The homogeneous phantom always yields a negative
      result, as expected. CONCLUSIONS: Detection is based on a statistical likelihood
      analysis to determine the presence of significantly different frequency response
      over the phantom, which is a novel approach to this problem. The overall results
      show promise and justify proof of concept trials with human subjects.

PMID- 24320475
TI  - Computer-aided detection and quantification of cavitary tuberculosis from CT
      scans.
AB  - PURPOSE: To present a computer-aided detection tool for identifying, quantifying,
      and evaluating tuberculosis (TB) cavities in the infected lungs from computed
      tomography (CT) scans. METHODS: The authors' proposed method is based on a novel
      shape-based automated detection algorithm on CT scans followed by a fuzzy
      connectedness (FC) delineation procedure. In order to assess interaction between
      cavities and airways, the authors first roughly identified air-filled structures
      (airway, cavities, esophagus, etc.) by thresholding over Hounsfield unit of CT
      image. Then, airway and cavity structure detection was conducted within the
      support vector machine classification algorithm. Once airway and cavities were
      detected automatically, the authors extracted airway tree using a hybrid
      multiscale approach based on novel affinity relations within the FC framework and
      segmented cavities using intensity-based FC algorithm. At final step, the authors
      refined airway structures within the local regions of FC with finer control.
      Cavity segmentation results were compared to the reference truths provided by
      expert radiologists and cavity formation was tracked longitudinally from serial
      CT scans through shape and volume information automatically determined through
      the authors' proposed system. Morphological evolution of the cavitary TB were
      analyzed accordingly with this process. Finally, the authors computed the minimum
      distance between cavity surface and nearby airway structures by using the linear
      time distance transform algorithm to explore potential role of airways in cavity
      formation and morphological evolution. RESULTS: The proposed methodology was
      qualitatively and quantitatively evaluated on pulmonary CT images of rabbits
      experimentally infected with TB, and multiple markers such as cavity volume,
      cavity surface area, minimum distance from cavity surface to the nearest
      bronchial-tree, and longitudinal change of these markers (namely, morphological
      evolution of cavities) were determined precisely. While accuracy of the authors'
      cavity detection algorithm was 94.61%, airway detection part of the proposed
      methodology showed even higher performance by 99.8%. Dice similarity coefficients
      for cavitary segmentation experiments were found to be approximately 99.0% with
      respect to the reference truths provided by two expert radiologists (blinded to
      their evaluations). Moreover, the authors noted that volume derived from the
      authors' segmentation method was highly correlated with those provided by the
      expert radiologists (R(2) = 0.99757 and R(2) = 0.99496, p < 0.001, with respect
      to the observer 1 and observer 2) with an interobserver agreement of 98%. The
      authors quantitatively confirmed that cavity formation was positioned by the
      nearby bronchial-tree after exploring the respective spatial positions based on
      the minimum distance measurement. In terms of efficiency, the core algorithms
      take less than 2 min on a linux machine with 3.47 GHz CPU and 24 GB memory.
      CONCLUSION: The authors presented a fully automatic method for cavitary TB
      detection, quantification, and evaluation. The performance of every step of the
      algorithm was qualitatively and quantitatively assessed. With the proposed
      method, airways and cavities were automatically detected and subsequently
      delineated in high accuracy with heightened efficiency. Furthermore, not only
      morphological information of cavities were obtained through the authors' proposed
      framework, but their spatial relation to airways, and longitudinal analysis was
      also provided to get further insight on cavity formation in tuberculosis disease.
      To the authors' best of knowledge, this is the first study in computerized
      analysis of cavitary tuberculosis from CT scans.

PMID- 24320476
TI  - Investigation of the effects of cell model and subcellular location of gold
      nanoparticles on nuclear dose enhancement factors using Monte Carlo simulation.
AB  - PURPOSE: The authors' aims were to model how various factors influence radiation
      dose enhancement by gold nanoparticles (AuNPs) and to propose a new modeling
      approach to the dose enhancement factor (DEF). METHODS: The authors used Monte
      Carlo N-particle (MCNP 5) computer code to simulate photon and electron transport
      in cells. The authors modeled human breast cancer cells as a single cell, a
      monolayer, or a cluster of cells. Different numbers of 5, 30, or 50 nm AuNPs were
      placed in the extracellular space, on the cell surface, in the cytoplasm, or in
      the nucleus. Photon sources examined in the simulation included nine
      monoenergetic x-rays (10-100 keV), an x-ray beam (100 kVp), and (125)I and
      (103)Pd brachytherapy seeds. Both nuclear and cellular dose enhancement factors
      (NDEFs, CDEFs) were calculated. The ability of these metrics to predict the
      experimental DEF based on the clonogenic survival of MDA-MB-361 human breast
      cancer cells exposed to AuNPs and x-rays were compared. RESULTS: NDEFs show a
      strong dependence on photon energies with peaks at 15, 30/40, and 90 keV. Cell
      model and subcellular location of AuNPs influence the peak position and value of
      NDEF. NDEFs decrease in the order of AuNPs in the nucleus, cytoplasm, cell
      membrane, and extracellular space. NDEFs also decrease in the order of AuNPs in a
      cell cluster, monolayer, and single cell if the photon energy is larger than 20
      keV. NDEFs depend linearly on the number of AuNPs per cell. Similar trends were
      observed for CDEFs. NDEFs using the monolayer cell model were more predictive
      than either single cell or cluster cell models of the DEFs experimentally derived
      from the clonogenic survival of cells cultured as a monolayer. The amount of
      AuNPs required to double the prescribed dose in terms of mg Au/g tissue decreases
      as the size of AuNPs increases, especially when AuNPs are in the nucleus and the
      cytoplasm. For 40 keV x-rays and a cluster of cells, to double the prescribed x
      ray dose (NDEF = 2) using 30 nm AuNPs, would require 5.1 +/- 0.2, 9 +/- 1, 10 +/-
      1, 10 +/- 1 mg Au/g tissue in the nucleus, in the cytoplasm, on the cell surface,
      or in the extracellular space, respectively. Using 50 nm AuNPs, the required
      amount decreases to 3.1 +/- 0.3, 8 +/- 1, 9 +/- 1, 9 +/- 1 mg Au/g tissue,
      respectively. CONCLUSIONS: NDEF is a new metric that can predict the radiation
      enhancement of AuNPs for various experimental conditions. Cell model, the
      subcellular location and size of AuNPs, and the number of AuNPs per cell, as well
      as the x-ray photon energy all have effects on NDEFs. Larger AuNPs in the nucleus
      of cluster cells exposed to x-rays of 15 or 40 keV maximize NDEFs.

PMID- 24320477
TI  - International workshop on non-ionizing radiation protection in medicine.
AB  - An international workshop brought together a range of stakeholders to consider
      protection from non-ionizing radiation used in medicine, research and cosmetics.
      Presentations on specific topics were followed by a general discussion on
      possible improvements in protection. Participants considered that adherence to
      science-based, harmonized exposure guidelines to limit exposures for clinical
      staff and other workers was a key prerequisite to safety in all situations. In
      addition, to engender an awareness of the risks involved to both the patient as
      well as the operator, equipment should be operated only by suitably qualified
      persons who have received appropriate training in the safe use of that device.
      This training should be carried out under the auspices of an accredited safety
      provider, and preferably offer a recognized qualification. Specific advice
      included the necessity for correct eye protection with higher power optical
      radiation sources, and avoiding the use of ultrasound for all exposures without
      medical benefit. Finally, the possibility of a harmonized approach to safety for
      both non-ionizing and ionizing radiation was considered worthy of further
      discussion. 

PMID- 24320478
TI  - Comment on "Transconvolution and the virtual positron emission tomograph: A new
      method for cross calibration in quantitative PET/CT imaging" [Med. Phys. 40,
      062503 (15pp.) (2013)].

PMID- 24320479
TI  - Response to "Comment on 'Transconvolution and the virtual positron emission
      tomograph (vPET): a new method for cross calibration in quantitative PET/CT
      imaging' " [Med. Phys. 40, 062503 (15pp.) (2013)].

PMID- 24320486
TI  - Point/counterpoint. Resolution modeling enhances PET imaging.

PMID- 24320487
TI  - A technique for estimating 4D-CBCT using prior knowledge and limited-angle
      projections.
AB  - PURPOSE: To develop a technique to estimate onboard 4D-CBCT using prior
      information and limited-angle projections for potential 4D target verification of
      lung radiotherapy. METHODS: Each phase of onboard 4D-CBCT is considered as a
      deformation from one selected phase (prior volume) of the planning 4D-CT. The
      deformation field maps (DFMs) are solved using a motion modeling and free-form
      deformation (MM-FD) technique. In the MM-FD technique, the DFMs are estimated
      using a motion model which is extracted from planning 4D-CT based on principal
      component analysis (PCA). The motion model parameters are optimized by matching
      the digitally reconstructed radiographs of the deformed volumes to the limited
      angle onboard projections (data fidelity constraint). Afterward, the estimated
      DFMs are fine-tuned using a FD model based on data fidelity constraint and
      deformation energy minimization. The 4D digital extended-cardiac-torso phantom
      was used to evaluate the MM-FD technique. A lung patient with a 30 mm diameter
      lesion was simulated with various anatomical and respirational changes from
      planning 4D-CT to onboard volume, including changes of respiration amplitude,
      lesion size and lesion average-position, and phase shift between lesion and body
      respiratory cycle. The lesions were contoured in both the estimated and "ground
      truth" onboard 4D-CBCT for comparison. 3D volume percentage-difference (VPD) and
      center-of-mass shift (COMS) were calculated to evaluate the estimation accuracy
      of three techniques: MM-FD, MM-only, and FD-only. Different onboard projection
      acquisition scenarios and projection noise levels were simulated to investigate
      their effects on the estimation accuracy. RESULTS: For all simulated patient and
      projection acquisition scenarios, the mean VPD (+/-S.D.)/COMS (+/-S.D.) between
      lesions in prior images and "ground-truth" onboard images were 136.11% (+/
      42.76%)/15.5 mm (+/-3.9 mm). Using orthogonal-view 15 degrees -each scan angle,
      the mean VPD/COMS between the lesion in estimated and "ground-truth" onboard
      images for MM-only, FD-only, and MM-FD techniques were 60.10% (+/-27.17%)/4.9 mm
      (+/-3.0 mm), 96.07% (+/-31.48%)/12.1 mm (+/-3.9 mm) and 11.45% (+/-9.37%)/1.3 mm
      (+/-1.3 mm), respectively. For orthogonal-view 30 degrees -each scan angle, the
      corresponding results were 59.16% (+/-26.66%)/4.9 mm (+/-3.0 mm), 75.98% (+/
      27.21%)/9.9 mm (+/-4.0 mm), and 5.22% (+/-2.12%)/0.5 mm (+/-0.4 mm). For single
      view scan angles of 3 degrees , 30 degrees , and 60 degrees , the results for MM
      FD technique were 32.77% (+/-17.87%)/3.2 mm (+/-2.2 mm), 24.57% (+/-18.18%)/2.9
      mm (+/-2.0 mm), and 10.48% (+/-9.50%)/1.1 mm (+/-1.3 mm), respectively. For
      projection angular-sampling-intervals of 0.6 degrees , 1.2 degrees , and 2.5
      degrees  with the orthogonal-view 30 degrees -each scan angle, the MM-FD
      technique generated similar VPD (maximum deviation 2.91%) and COMS (maximum
      deviation 0.6 mm), while sparser sampling yielded larger VPD/COMS. With equal
      number of projections, the estimation results using scattered 360 degrees  scan
      angle were slightly better than those using orthogonal-view 30 degrees -each scan
      angle. The estimation accuracy of MM-FD technique declined as noise level
      increased. CONCLUSIONS: The MM-FD technique substantially improves the estimation
      accuracy for onboard 4D-CBCT using prior planning 4D-CT and limited-angle
      projections, compared to the MM-only and FD-only techniques. It can potentially
      be used for the inter/intrafractional 4D-localization verification.

PMID- 24320488
TI  - Evaluation of the dosimetric properties of a synthetic single crystal diamond
      detector in high energy clinical proton beams.
AB  - PURPOSE: To investigate the dosimetric properties of a synthetic single crystal
      diamond Schottky diode for accurate relative dose measurements in large and small
      field high-energy clinical proton beams. METHODS: The dosimetric properties of a
      synthetic single crystal diamond detector were assessed by comparison with a
      reference Markus parallel plate ionization chamber, an Exradin A16
      microionization chamber, and Exradin T1a ion chamber. The diamond detector was
      operated at zero bias voltage at all times. Comparative dose distribution
      measurements were performed by means of Fractional depth dose curves and lateral
      beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm
      square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass
      collimators. ICRU Report No. 78 recommended beam parameters were used to compare
      fractional depth dose curves and beam profiles obtained using the diamond
      detector and the reference ionization chamber. Warm-up/stability of the detector
      response and linearity with dose were evaluated in a 250 MeV proton beam and dose
      rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the
      azimuthal angle dependence of the diode response were also evaluated. RESULTS: A
      maximum deviation in diamond detector signal from the average reading of less
      than 0.5% was found during the warm-up irradiation procedure. The detector
      response showed a good linear behavior as a function of dose with observed
      deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response
      was dose rate independent, with deviations below 0.5% in the investigated dose
      rates ranging from 85 to 300 cGy/min. Stem effect and azimuthal angle dependence
      of the diode signal were within 0.5%. Fractional depth dose curves and lateral
      beam profiles obtained with the diamond detector were in good agreement with
      those measured using reference dosimeters. CONCLUSIONS: The observed dosimetric
      properties of the synthetic single crystal diamond detector indicate that its
      behavior is proton energy independent and dose rate independent in the
      investigated energy and dose rate range and it is suitable for accurate relative
      dosimetric measurements in large as well as in small field high energy clinical
      proton beams.

PMID- 24320489
TI  - Dynamic rotating-shield brachytherapy.
AB  - PURPOSE: To present dynamic rotating shield brachytherapy (D-RSBT), a novel form
      of high-dose-rate brachytherapy (HDR-BT) with electronic brachytherapy source,
      where the radiation shield is capable of changing emission angles during the
      radiation delivery process. METHODS: A D-RSBT system uses two layers of
      independently rotating tungsten alloy shields, each with a 180 degrees  azimuthal
      emission angle. The D-RSBT planning is separated into two stages: anchor plan
      optimization and optimal sequencing. In the anchor plan optimization, anchor
      plans are generated by maximizing the D90 for the high-risk clinical-tumor-volume
      (HR-CTV) assuming a fixed azimuthal emission angle of 11.25 degrees . In the
      optimal sequencing, treatment plans that most closely approximate the anchor
      plans under the delivery-time constraint will be efficiently computed. Treatment
      plans for five cervical cancer patients were generated for D-RSBT, single-shield
      RSBT (S-RSBT), and (192)Ir-based intracavitary brachytherapy with supplementary
      interstitial brachytherapy (IS + ICBT) assuming five treatment fractions.
      External beam radiotherapy doses of 45 Gy in 25 fractions of 1.8 Gy each were
      accounted for. The high-risk clinical target volume (HR-CTV) doses were escalated
      such that the D2cc of the rectum, sigmoid colon, or bladder reached its tolerance
      equivalent dose in 2 Gy fractions (EQD2 with alpha/beta = 3 Gy) of 75 Gy, 75 Gy,
      or 90 Gy, respectively. RESULTS: For the patients considered, IS + ICBT had an
      average total dwell time of 5.7 minutes/fraction (min/fx) assuming a 10 Ci(192)Ir
      source, and the average HR-CTV D90 was 78.9 Gy. In order to match the HR-CTV D90
      of IS + ICBT, D-RSBT required an average of 10.1 min/fx more delivery time, and S
      RSBT required 6.7 min/fx more. If an additional 20 min/fx of delivery time is
      allowed beyond that of the IS + ICBT case, D-RSBT and S-RSBT increased the HR-CTV
      D90 above IS + ICBT by an average of 16.3 Gy and 9.1 Gy, respectively.
      CONCLUSIONS: For cervical cancer patients, D-RSBT can boost HR-CTV D90 over IS +
      ICBT and S-RSBT without violating the tolerance doses to the bladder, rectum, or
      sigmoid. The D90 improvements from D-RSBT depend on the patient, the delivery
      time budget, and the applicator structure.

PMID- 24320490
TI  - Modeling the dosimetry of organ-at-risk in head and neck IMRT planning: an
      intertechnique and interinstitutional study.
AB  - PURPOSE: To build a statistical model to quantitatively correlate the anatomic
      features of structures and the corresponding dose-volume histogram (DVH) of head
      and neck (HN) Tomotherapy (Tomo) plans. To study if the model built upon one
      intensity modulated radiation therapy (IMRT) technique (such as conventional
      Linac) can be used to predict anticipated organs-at-risk (OAR) DVH of patients
      treated with a different IMRT technique (such as Tomo). To study if the model
      built upon the clinical experience of one institution can be used to aid IMRT
      planning for another institution. METHODS: Forty-four Tomotherapy intensity
      modulate radiotherapy plans of HN cases (Tomo-IMRT) from Institution A were
      included in the study. A different patient group of 53 HN fixed gantry IMRT (FG
      IMRT) plans was selected from Institution B. The analyzed OARs included the
      parotid, larynx, spinal cord, brainstem, and submandibular gland. Two major
      groups of anatomical features were considered: the volumetric information and the
      spatial information. The volume information includes the volume of target, OAR,
      and overlapped volume between target and OAR. The spatial information of OARs
      relative to PTVs was represented by the distance-to-target histogram (DTH).
      Important anatomical and dosimetric features were extracted from DTH and DVH by
      principal component analysis. Two regression models, one for Tomotherapy plan and
      one for IMRT plan, were built independently. The accuracy of intratreatment
      modality model prediction was validated by a leave one out cross-validation
      method. The intertechnique and interinstitution validations were performed by
      using the FG-IMRT model to predict the OAR dosimetry of Tomo-IMRT plans. The
      dosimetry of OARs, under the same and different institutional preferences, was
      analyzed to examine the correlation between the model prediction and planning
      protocol. RESULTS: Significant patient anatomical factors contributing to OAR
      dose sparing in HN Tomotherapy plans have been analyzed and identified. For all
      the OARs, the discrepancies of dose indices between the model predicted values
      and the actual plan values were within 2.1%. Similar results were obtained from
      the modeling of FG-IMRT plans. The parotid gland was spared in a comparable
      fashion during the treatment planning of two institutions. The model based on FG
      IMRT plans was found to predict the median dose of the parotid of Tomotherapy
      plans quite well, with a mean error of 2.6%. Predictions from the FG-IMRT model
      suggested the median dose of the larynx, median dose of the brainstem and D2 of
      the brainstem could be reduced by 10.5%, 12.8%, and 20.4%, respectively, in the
      Tomo-IMRT plans. This was found to be correlated to the institutional differences
      in OAR constraint settings. Re-planning of six Tomotherapy patients confirmed the
      potential of optimization improvement predicted by the FG-IMRT model was correct.
      CONCLUSIONS: The authors established a mathematical model to correlate the
      anatomical features and dosimetric indexes of OARs of HN patients in Tomotherapy
      plans. The model can be used for the setup of patient-specific OAR dose sparing
      goals and quality control of planning results.The institutional clinical
      experience was incorporated into the model which allows the model from one
      institution to generate a reference plan for another institution, or another IMRT
      technique.

PMID- 24320491
TI  - Impact of the MLC on the MRI field distortion of a prototype MRI-linac.
AB  - PURPOSE: To cope with intrafraction tumor motion, integrated MRI-linac systems
      for real-time image guidance are currently under development. The multileaf
      collimator (MLC) is a key component in every state-of-the-art radiotherapy
      treatment system, allowing for accurate field shaping and tumor tracking. This
      work quantifies the magnetic impact of a widely used MLC on the MRI field
      homogeneity for such a modality. METHODS: The finite element method was employed
      to model a MRI-linac assembly comprised of a 1.0 T split-bore MRI magnet and the
      key ferromagnetic components of a Varian Millennium 120 MLC, namely, the leaves
      and motors. Full 3D magnetic field maps of the system were generated. From these
      field maps, the peak-to-peak distortion within the MRI imaging volume was
      evaluated over a 30 cm diameter sphere volume (DSV) around the isocenter and
      compared to a maximum preshim inhomogeneity of 300 MUT. Five parametric studies
      were performed: (1) The source-to-isocenter distance (SID) was varied from 100 to
      200 cm, to span the range of a compact system to that with lower magnetic
      coupling. (2) The MLC model was changed from leaves only to leaves with motors,
      to determine the contribution to the total distortion caused by MLC leaves and
      motors separately. (3) The system was configured in the inline or perpendicular
      orientation, i.e., the linac treatment beam was oriented parallel or
      perpendicular to the magnetic field direction. (4) The treatment field size was
      varied from 0 * 0 to 20*20 cm(2), to span the range of clinical treatment fields.
      (5) The coil currents were scaled linearly to produce magnetic field strengths B0
      of 0.5, 1.0, and 1.5 T, to estimate how the MLC impact changes with B0. RESULTS:
      (1) The MLC-induced MRI field distortion fell continuously with increasing SID.
      (2) MLC leaves and motors were found to contribute to the distortion in
      approximately equal measure. (3) Due to faster falloff of the fringe field, the
      field distortion was generally smaller in the perpendicular beam orientation. The
      peak-to-peak DSV distortion was below 300 MUT at SID>=130 cm (perpendicular) and
      SID>=140 cm (inline) for the 1.0 T design. (4) The simulation of different
      treatment fields was identified to cause dynamic changes in the field
      distribution. However, the estimated residual distortion was below 1.2 mm
      geometric distortion at SID>=120 cm (perpendicular) and SID>=130 cm (inline) for
      a 10 mT/m frequency-encoding gradient. (5) Due to magnetic saturation of the MLC
      materials, the field distortion remained constant at B0>1.0 T. CONCLUSIONS: This
      work shows that the MRI field distortions caused by the MLC cannot be ignored and
      must be thoroughly investigated for any MRI-linac system. The numeric distortion
      values obtained for our 1.0 T magnet may vary for other magnet designs with
      substantially different fringe fields, however the concept of modest increases in
      the SID to reduce the distortion to a shimmable level is generally applicable.

PMID- 24320492
TI  - Predicting objective function weights from patient anatomy in prostate IMRT
      treatment planning.
AB  - PURPOSE: Intensity-modulated radiation therapy (IMRT) treatment planning
      typically combines multiple criteria into a single objective function by taking a
      weighted sum. The authors propose a statistical model that predicts objective
      function weights from patient anatomy for prostate IMRT treatment planning. This
      study provides a proof of concept for geometry-driven weight determination.
      METHODS: A previously developed inverse optimization method (IOM) was used to
      generate optimal objective function weights for 24 patients using their
      historical treatment plans (i.e., dose distributions). These IOM weights were
      around 1% for each of the femoral heads, while bladder and rectum weights varied
      greatly between patients. A regression model was developed to predict a patient's
      rectum weight using the ratio of the overlap volume of the rectum and bladder
      with the planning target volume at a 1 cm expansion as the independent variable.
      The femoral head weights were fixed to 1% each and the bladder weight was
      calculated as one minus the rectum and femoral head weights. The model was
      validated using leave-one-out cross validation. Objective values and dose
      distributions generated through inverse planning using the predicted weights were
      compared to those generated using the original IOM weights, as well as an average
      of the IOM weights across all patients. RESULTS: The IOM weight vectors were on
      average six times closer to the predicted weight vectors than to the average
      weight vector, using l2 distance. Likewise, the bladder and rectum objective
      values achieved by the predicted weights were more similar to the objective
      values achieved by the IOM weights. The difference in objective value performance
      between the predicted and average weights was statistically significant according
      to a one-sided sign test. For all patients, the difference in rectum V54.3 Gy,
      rectum V70.0 Gy, bladder V54.3 Gy, and bladder V70.0 Gy values between the dose
      distributions generated by the predicted weights and IOM weights was less than 5
      percentage points. Similarly, the difference in femoral head V54.3 Gy values
      between the two dose distributions was less than 5 percentage points for all but
      one patient. CONCLUSIONS: This study demonstrates a proof of concept that patient
      anatomy can be used to predict appropriate objective function weights for
      treatment planning. In the long term, such geometry-driven weights may serve as a
      starting point for iterative treatment plan design or may provide information
      about the most clinically relevant region of the Pareto surface to explore.

PMID- 24320493
TI  - Patient-specific QA and delivery verification of scanned ion beam at NIRS-HIMAC.
AB  - PURPOSE: To evaluate a patient-specific QA program and system for constancy
      checking of a scanning delivery system developed at the National Institute of
      Radiological Sciences. METHODS: For the patient-specific QA, all the planned
      beams are recalculated on a water phantom with treatment planning software (TPS).
      The recalculated dose distributions are compared with the measured distributions
      using a 2D ionization chamber array at several depths, and evaluated using gamma
      index analysis with criteria of 3% and 3 mm and a pass rate of 90%. For the
      constancy check, the authors developed the multiwire proportional chamber (MWPC),
      which can record the delivered 2D fluence images in a slice-by-slice manner.
      During irradiation for dosimetric QA with the 2D ionization chamber array and an
      accordion-type water phantom, the 2D fluence images are recorded using the MWPC
      in the delivery system. These recorded images are then compared to those taken in
      the treatment session to check the constancy check. This analysis also employs
      gamma index analysis using the same criteria as in the patient-specific QA. These
      patient-specific QA and constancy check evaluations were performed using the data
      of 122 patients. RESULTS: In the patient-specific QA, the measured dose
      distributions agreed well with those calculated by the TPS, and the QA criteria
      were satisfied in all measurements. The additional check of the fluence
      comparison ensured the constancy of the delivered field during each treatment
      irradiation. CONCLUSIONS: The authors established a patient-specific QA program
      and additional check of delivery constancy in every treatment session. Fluence
      comparison is a strong tool for constancy checking of the delivery system.

PMID- 24320495
TI  - I-125 ROPES eye plaque dosimetry: validation of a commercial 3D ophthalmic
      brachytherapy treatment planning system and independent dose calculation software
      with GafChromic(r) EBT3 films.
AB  - PURPOSE: The purpose of this study was to measure the dose distributions for
      different Radiation Oncology Physics and Engineering Services, Australia (ROPES)
      type eye plaques loaded with I-125 (model 6711) seeds using GafChromic((r)) EBT3
      films, in order to verify the dose distributions in the Plaque SimulatorTM (PS)
      ophthalmic 3D treatment planning system. The brachytherapy module of RADCALC((r))
      was used to independently check the dose distributions calculated by PS.
      Correction factors were derived from the measured data to be used in PS to
      account for the effect of the stainless steel ROPES plaque backing on the 3D dose
      distribution. METHODS: Using GafChromic((r)) EBT3 films inserted in a specially
      designed Solid WaterTM eye ball phantom, dose distributions were measured three
      dimensionally both along and perpendicular to I-125 (model 6711) loaded ROPES eye
      plaque's central axis (CAX) with 2 mm depth increments. Each measurement was
      performed in full scatter conditions both with and without the stainless steel
      plaque backing attached to the eye plaque, to assess its effect on the dose
      distributions. Results were compared to the dose distributions calculated by
      Plaque SimulatorTM and checked independently with RADCALC((r)). RESULTS: The EBT3
      film measurements without the stainless steel backing were found to agree with PS
      and RADCALC((r)) to within 2% and 4%, respectively, on the plaque CAX. Also,
      RADCALC((r)) was found to agree with PS to within 2%. The CAX depth doses
      measured using EBT3 film with the stainless steel backing were observed to result
      in a 4% decrease relative to when the backing was not present. Within
      experimental uncertainty, the 4% decrease was found to be constant with depth and
      independent of plaque size. Using a constant dose correction factor of T = 0.96
      in PS, where the calculated dose for the full water scattering medium is reduced
      by 4% in every voxel in the dose grid, the effect of the plaque backing was
      accurately modeled in the planning system. Off-axis profiles were also modeled in
      PS by taking into account the three-dimensional model of the plaque backing.
      CONCLUSIONS: The doses calculated by PS and RADCALC((r)) for uniformly loaded
      ROPES plaques in full and uniform scattering conditions were validated by the
      EBT3 film measurements. The stainless steel plaque backing was observed to
      decrease the measured dose by 4%. Through the introduction of a scalar correction
      factor (0.96) in PS, the dose homogeneity effect of the stainless steel plaque
      backing was found to agree with the measured EBT3 film measurements.

PMID- 24320494
TI  - Improving spot-scanning proton therapy patient specific quality assurance with
      HPlusQA, a second-check dose calculation engine.
AB  - PURPOSE: The purpose of this study was to validate the use of HPlusQA, spot
      scanning proton therapy (SSPT) dose calculation software developed at The
      University of Texas MD Anderson Cancer Center, as second-check dose calculation
      software for patient-specific quality assurance (PSQA). The authors also showed
      how HPlusQA can be used within the current PSQA framework. METHODS: The authors
      compared the dose calculations of HPlusQA and the Eclipse treatment planning
      system with 106 planar dose measurements made as part of PSQA. To determine the
      relative performance and the degree of correlation between HPlusQA and Eclipse,
      the authors compared calculated with measured point doses. Then, to determine how
      well HPlusQA can predict when the comparisons between Eclipse calculations and
      the measured dose will exceed tolerance levels, the authors compared gamma index
      scores for HPlusQA versus Eclipse with those of measured doses versus Eclipse.
      The authors introduce the alphabetagamma transformation as a way to more easily
      compare gamma scores. RESULTS: The authors compared measured and calculated dose
      planes using the relative depth, z/R * 100%, where z is the depth of the
      measurement and R is the proton beam range. For relative depths than less than
      80%, both Eclipse and HPlusQA calculations were within 2 cGy of dose measurements
      on average. When the relative depth was greater than 80%, the agreement between
      the calculations and measurements fell to 4 cGy. For relative depths less than
      10%, the Eclipse and HPlusQA dose discrepancies showed a negative correlation, 
      0.21. Otherwise, the correlation between the dose discrepancies was positive and
      as large as 0.6. For the dose planes in this study, HPlusQA correctly predicted
      when Eclipse had and had not calculated the dose to within tolerance 92% and 79%
      of the time, respectively. In 4 of 106 cases, HPlusQA failed to predict when the
      comparison between measurement and Eclipse's calculation had exceeded the
      tolerance levels of 3% for dose and 3 mm for distance-to-agreement. CONCLUSIONS:
      The authors found HPlusQA to be reasonably effective (79% +/- 10%) in determining
      when the comparison between measured dose planes and the dose planes calculated
      by the Eclipse treatment planning system had exceeded the acceptable tolerance
      levels. When used as described in this study, HPlusQA can reduce the need for
      patient specific quality assurance measurements by 64%. The authors believe that
      the use of HPlusQA as a dose calculation second check can increase the efficiency
      and effectiveness of the QA process.

PMID- 24320496
TI  - Motion-map constrained image reconstruction (MCIR): application to four
      dimensional cone-beam computed tomography.
AB  - PURPOSE: Utilization of respiratory correlated four-dimensional cone-beam
      computed tomography (4DCBCT) has enabled verification of internal target motion
      and volume immediately prior to treatment. However, with current standard CBCT
      scan, 4DCBCT poses challenge for reconstruction due to the fact that multiple
      phase binning leads to insufficient number of projection data to reconstruct and
      thus cause streaking artifacts. The purpose of this study is to develop a novel
      4DCBCT reconstruction algorithm framework called motion-map constrained image
      reconstruction (MCIR), that allows reconstruction of high quality and high phase
      resolution 4DCBCT images with no more than the imaging dose as well as
      projections used in a standard free breathing 3DCBCT (FB-3DCBCT) scan. METHODS:
      The unknown 4DCBCT volume at each phase was mathematically modeled as a
      combination of FB-3DCBCT and phase-specific update vector which has an associated
      motion-map matrix. The motion-map matrix, which is the key innovation of the MCIR
      algorithm, was defined as the matrix that distinguishes voxels that are moving
      from stationary ones. This 4DCBCT model was then reconstructed with compressed
      sensing (CS) reconstruction framework such that the voxels with high motion would
      be aggressively updated by the phase-wise sorted projections and the voxels with
      less motion would be minimally updated to preserve the FB-3DCBCT. To evaluate the
      performance of our proposed MCIR algorithm, we evaluated both numerical phantoms
      and a lung cancer patient. The results were then compared with the (1) clinical
      FB-3DCBCT reconstructed using the FDK, (2) 4DCBCT reconstructed using the FDK,
      and (3) 4DCBCT reconstructed using the well-known prior image constrained
      compressed sensing (PICCS). RESULTS: Examination of the MCIR algorithm showed
      that high phase-resolved 4DCBCT with sets of up to 20 phases using a typical FB
      3DCBCT scan could be reconstructed without compromising the image quality.
      Moreover, in comparison with other published algorithms, the image quality of the
      MCIR algorithm is shown to be excellent. CONCLUSIONS: This work demonstrates the
      potential for providing high-quality 4DCBCT during on-line image-guided radiation
      therapy (IGRT), without increasing the imaging dose. The results showed that (at
      least) 20 phase images could be reconstructed using the same projections data,
      used to reconstruct a single FB-3DCBCT, without streak artifacts that are caused
      by insufficient projections.

PMID- 24320497
TI  - Tomotherapy treatment plan quality assurance: the impact of applied criteria on
      passing rate in gamma index method.
AB  - PURPOSE: Pretreatment patient plan verification with gamma index (GI) metric
      analysis is standard procedure for intensity modulated radiation therapy (IMRT)
      treatment. The aim of this paper is to evaluate the variability of the local and
      global gamma index obtained during standard pretreatment quality assurance (QA)
      measurements for plans performed with Tomotherapy unit. The QA measurements were
      performed with a 3D diode array, using variable passing criteria: 3%/3 mm, 2%/2
      mm, 1%/1 mm, each with both local and global normalization. METHODS: The authors
      analyzed the pretreatment QA results for 73 verifications; 37 were prostate
      cancer plans, 16 were head and neck plans, and 20 were other clinical sites. All
      plans were treated using the Tomotherapy Hi-Art System. Pretreatment QA plans
      were performed with the commercially available 3D diode array ArcCHECKTM. This
      device has 1386 diodes arranged in a helical geometry spaced 1 cm apart. The dose
      measurements were acquired on the ArcCHECKTM and then compared with the
      calculated dose using the standard gamma analysis method. The gamma passing rate
      (%GP), defined as the percentage of points satisfying the condition GI < 1, was
      calculated for different criteria (3%/3 mm, 2%/2 mm, 1%/1 mm) and for both global
      and local normalization. In the case of local normalization method, the authors
      set three dose difference threshold (DDT) values of 2, 3, and 5 cGy. Dose
      difference threshold is defined as the minimum absolute dose error considered in
      the analysis when using local normalization. Low-dose thresholds (TH) of 5% and
      10% were also applied and analyzed. RESULTS: Performing a paired-t-test, the
      authors determined that the gamma passing rate is independent of the threshold
      values for all of the adopted criteria (5%TH vs 10%TH, p > 0.1). Our findings
      showed that mean %GPs for local (or global) normalization for the entire study
      group were 93% (98%), 84% (92%), and 66% (61%) for 3%/3 mm, 2%/2 mm, and 1%/1 mm
      criteria, respectively. DDT was equal to 2 cGy for the local normalization
      analysis cases. The authors observed great variability in the resulting %GP. With
      3%/3 mm gamma criteria, the overall passing rate with local normalization was
      4.6% less on the average than with global one, as expected. The wide difference
      between %GP calculated with global or local approach is also confirmed by an
      unpaired t-test statistical analysis. CONCLUSIONS: The variability of %GP
      obtained confirmed the necessity to establish defined agreement criteria that
      could be universal and comparable between institutions. In particular, while the
      gamma passing rate does not depend on the choice of threshold, the choice of DDT
      strongly influences the gamma passing rate for local calculations. The difference
      between global and local %GP was statistically significant for prostate and other
      treatment sites when DDT was changed from 2 to 3 cGy.

PMID- 24320498
TI  - Patient-specific quantification of respiratory motion-induced dose uncertainty
      for step-and-shoot IMRT of lung cancer.
AB  - PURPOSE: The objective of this study was to quantify respiratory motion-induced
      dose uncertainty at the planning stage for step-and-shoot intensity-modulated
      radiation therapy (IMRT) using an analytical technique. METHODS: Ten patients
      with stage II/III lung cancer who had undergone a planning four-dimensional (4D)
      computed tomographic scan and step-and-shoot IMRT planning were selected with a
      mix of motion and tumor size for this retrospective study. A step-and-shoot IMRT
      plan was generated for each patient. The maximum and minimum doses with
      respiratory motion were calculated for each plan, and the mean deviation from the
      4D dose was calculated, taking delivery time, fractionation, and patient
      breathing cycle into consideration. RESULTS: For all patients evaluated in this
      study, the mean deviation from the 4D dose in the planning target volume (PTV)
      was <2.5%, with a standard deviation <1.2%, and maximum point dose variation from
      the 4D dose was <6.2% in the PTV assuming delivery dose rate of 200 MU/min and
      patient breathing cycle of 8 s. The motion-induced dose uncertainty is a function
      of motion, fractionation, MU (plan modulation), dose rate, and patient breathing
      cycle. CONCLUSIONS: Respiratory motion-induced dose uncertainty varies from
      patient to patient. Therefore, it is important to evaluate the dose uncertainty
      on a patient-specific basis, which could be useful for plan evaluation and
      treatment strategy determination for selected patients.

PMID- 24320499
TI  - Four-dimensional Monte Carlo simulations demonstrating how the extent of
      intensity-modulation impacts motion effects in proton therapy lung treatments.
AB  - PURPOSE: To compare motion effects in intensity modulated proton therapy (IMPT)
      lung treatments with different levels of intensity modulation. METHODS: Spot
      scanning IMPT treatment plans were generated for ten lung cancer patients for
      2.5Gy(RBE) and 12Gy(RBE) fractions and two distinct energy-dependent spot sizes
      (sigma ~8-17 mm and ~2-4 mm). IMPT plans were generated with the target
      homogeneity of each individual field restricted to <20% (IMPT20%). These plans
      were compared to full IMPT (IMPTfull), which had no restriction on the single
      field homogeneity. 4D Monte Carlo simulations were performed upon the patient
      4DCT geometry, including deformable image registration and incorporating the
      detailed timing structure of the proton delivery system. Motion effects were
      quantified via comparison of the results of the 4D simulations (4D-IMPT20%, 4D
      IMPTfull) with those of a 3D Monte Carlo simulation (3D-IMPT20%, 3D-IMPTfull)
      upon the planning CT using the equivalent uniform dose (EUD), V95 and D1-D99. The
      effects in normal lung were quantified using mean lung dose (MLD) and V90%.
      RESULTS: For 2.5Gy(RBE), the mean EUD for the large spot size is 99.9% +/- 2.8%
      for 4D-IMPT20% compared to 100.1% +/- 2.9% for 4D-IMPTfull. The corresponding
      values are 88.6% +/- 8.7% (4D-IMPT20%) and 91.0% +/- 9.3% (4D-IMPTfull) for the
      smaller spot size. The EUD value is higher in 69.7% of the considered deliveries
      for 4D-IMPTfull. The V95 is also higher in 74.7% of the plans for 4D-IMPTfull,
      implying that IMPTfull plans experience less underdose compared to IMPT20%.
      However, the target dose homogeneity is improved in the majority (67.8%) of plans
      for 4D-IMPT20%. The higher EUD and V95 suggests that the degraded homogeneity in
      IMPTfull is actually due to the introduction of hot spots in the target volume,
      perhaps resulting from the sharper in-target dose gradients. The greatest
      variations between the IMPT20% and IMPTfull deliveries are observed for patients
      with the largest motion amplitudes. These patients would likely be treated using
      gating or another motion mitigation technique, which was not the focus of this
      study. CONCLUSIONS: For the treatment parameters considered in this study, the
      differences between IMPTfull and IMPT20% are only likely to be clinically
      significant for patients with large (>20 mm) motion amplitudes.

PMID- 24320500
TI  - Monte Carlo and analytical model predictions of leakage neutron exposures from
      passively scattered proton therapy.
AB  - PURPOSE: Stray neutron radiation is of concern after radiation therapy,
      especially in children, because of the high risk it might carry for secondary
      cancers. Several previous studies predicted the stray neutron exposure from
      proton therapy, mostly using Monte Carlo simulations. Promising attempts to
      develop analytical models have also been reported, but these were limited to only
      a few proton beam energies. The purpose of this study was to develop an
      analytical model to predict leakage neutron equivalent dose from passively
      scattered proton beams in the 100-250-MeV interval. METHODS: To develop and
      validate the analytical model, the authors used values of equivalent dose per
      therapeutic absorbed dose (H/D) predicted with Monte Carlo simulations. The
      authors also characterized the behavior of the mean neutron radiation-weighting
      factor, wR, as a function of depth in a water phantom and distance from the beam
      central axis. RESULTS: The simulated and analytical predictions agreed well. On
      average, the percentage difference between the analytical model and the Monte
      Carlo simulations was 10% for the energies and positions studied. The authors
      found that wR was highest at the shallowest depth and decreased with depth until
      around 10 cm, where it started to increase slowly with depth. This was consistent
      among all energies. CONCLUSION: Simple analytical methods are promising
      alternatives to complex and slow Monte Carlo simulations to predict H/D values.
      The authors' results also provide improved understanding of the behavior of wR
      which strongly depends on depth, but is nearly independent of lateral distance
      from the beam central axis.

PMID- 24320501
TI  - Three independent one-dimensional margins for single-fraction frameless
      stereotactic radiosurgery brain cases using CBCT.
AB  - PURPOSE: Setting a proper margin is crucial for not only delivering the required
      radiation dose to a target volume, but also reducing the unnecessary radiation to
      the adjacent organs at risk. This study investigated the independent one
      dimensional symmetric and asymmetric margins between the clinical target volume
      (CTV) and the planning target volume (PTV) for linac-based single-fraction
      frameless stereotactic radiosurgery (SRS). METHODS: The authors assumed a Dirac
      delta function for the systematic error of a specific machine and a Gaussian
      function for the residual setup errors. Margin formulas were then derived in
      details to arrive at a suitable CTV-to-PTV margin for single-fraction frameless
      SRS. Such a margin ensured that the CTV would receive the prescribed dose in 95%
      of the patients. To validate our margin formalism, the authors retrospectively
      analyzed nine patients who were previously treated with noncoplanar conformal
      beams. Cone-beam computed tomography (CBCT) was used in the patient setup. The
      isocenter shifts between the CBCT and linac were measured for a Varian Trilogy
      linear accelerator for three months. For each plan, the authors shifted the
      isocenter of the plan in each direction by +/-3 mm simultaneously to simulate the
      worst setup scenario. Subsequently, the asymptotic behavior of the CTV V80% for
      each patient was studied as the setup error approached the CTV-PTV margin.
      RESULTS: The authors found that the proper margin for single-fraction frameless
      SRS cases with brain cancer was about 3 mm for the machine investigated in this
      study. The isocenter shifts between the CBCT and the linac remained almost
      constant over a period of three months for this specific machine. This confirmed
      our assumption that the machine systematic error distribution could be
      approximated as a delta function. This definition is especially relevant to a
      single-fraction treatment. The prescribed dose coverage for all the patients
      investigated was 96.1% +/- 5.5% with an extreme 3-mm setup error in all three
      directions simultaneously. It was found that the effect of the setup error on
      dose coverage was tumor location dependent. It mostly affected the tumors located
      in the posterior part of the brain, resulting in a minimum coverage of
      approximately 72%. This was entirely due to the unique geometry of the posterior
      head. CONCLUSIONS: Margin expansion formulas were derived for single-fraction
      frameless SRS such that the CTV would receive the prescribed dose in 95% of the
      patients treated for brain cancer. The margins defined in this study are machine
      specific and account for nonzero mean systematic error. The margin for single
      fraction SRS for a group of machines was also derived in this paper.

PMID- 24320502
TI  - Repopulation of interacting tumor cells during fractionated radiotherapy:
      stochastic modeling of the tumor control probability.
AB  - PURPOSE: Optimal treatment planning for fractionated external beam radiation
      therapy requires inputs from radiobiology based on recent thinking about the
      "five Rs" (repopulation, radiosensitivity, reoxygenation, redistribution, and
      repair). The need is especially acute for the newer, often individualized,
      protocols made feasible by progress in image guided radiation therapy and dose
      conformity. Current stochastic tumor control probability (TCP) models
      incorporating tumor repopulation effects consider "stem-like cancer cells" (SLCC)
      to be independent, but the authors here propose that SLCC-SLCC interactions may
      be significant. The authors present a new stochastic TCP model for repopulating
      SLCC interacting within microenvironmental niches. Our approach is meant mainly
      for comparing similar protocols. It aims at practical generalizations of previous
      mathematical models. METHODS: The authors consider protocols with complete
      sublethal damage repair between fractions. The authors use customized open-source
      software and recent mathematical approaches from stochastic process theory for
      calculating the time-dependent SLCC number and thereby estimating SLCC
      eradication probabilities. As specific numerical examples, the authors consider
      predicted TCP results for a 2 Gy per fraction, 60 Gy protocol compared to 64 Gy
      protocols involving early or late boosts in a limited volume to some fractions.
      RESULTS: In sample calculations with linear quadratic parameters alpha = 0.3 per
      Gy, alpha/beta = 10 Gy, boosting is predicted to raise TCP from a dismal 14.5%
      observed in some older protocols for advanced NSCLC to above 70%. This prediction
      is robust as regards: (a) the assumed values of parameters other than alpha and
      (b) the choice of models for intraniche SLCC-SLCC interactions. However, alpha =
      0.03 per Gy leads to a prediction of almost no improvement when boosting.
      CONCLUSIONS: The predicted efficacy of moderate boosts depends sensitively on
      alpha. Presumably, the larger values of alpha are the ones appropriate for
      individualized treatment protocols, with the smaller values relevant only to
      protocols for a heterogeneous patient population. On that assumption, boosting is
      predicted to be highly effective. Front boosting, apart from practical advantages
      and a possible advantage as regards iatrogenic second cancers, also probably
      gives a slightly higher TCP than back boosting. If the total number of SLCC at
      the start of treatment can be measured even roughly, it will provide a highly
      sensitive way of discriminating between various models and parameter choices.
      Updated mathematical methods for calculating repopulation allow credible
      generalizations of earlier results.

PMID- 24320503
TI  - Resolution enhancement of lung 4D-CT via group-sparsity.
AB  - PURPOSE: 4D-CT typically delivers more accurate information about anatomical
      structures in the lung, over 3D-CT, due to its ability to capture visual
      information of the lung motion across different respiratory phases. This helps to
      better determine the dose during radiation therapy for lung cancer. However, a
      critical concern with 4D-CT that substantially compromises this advantage is the
      low superior-inferior resolution due to less number of acquired slices, in order
      to control the CT radiation dose. To address this limitation, the authors propose
      an approach to reconstruct missing intermediate slices, so as to improve the
      superior-inferior resolution. METHODS: In this method the authors exploit the
      observation that sampling information across respiratory phases in 4D-CT can be
      complimentary due to lung motion. The authors' approach uses this locally
      complimentary information across phases in a patch-based sparse-representation
      framework. Moreover, unlike some recent approaches that treat local patches
      independently, the authors' approach employs the group-sparsity framework that
      imposes neighborhood and similarity constraints between patches. This helps in
      mitigating the trade-off between noise robustness and structure preservation,
      which is an important consideration in resolution enhancement. The authors
      discuss the regularizing ability of group-sparsity, which helps in reducing the
      effect of noise and enables better structural localization and enhancement.
      RESULTS: The authors perform extensive experiments on the publicly available DIR
      Lab Lung 4D-CT dataset [R. Castillo, E. Castillo, R. Guerra, V. Johnson, T.
      McPhail, A. Garg, and T. Guerrero, "A framework for evaluation of deformable
      image registration spatial accuracy using large landmark point sets," Phys. Med.
      Biol. 54, 1849-1870 (2009)]. First, the authors carry out empirical parametric
      analysis of some important parameters in their approach. The authors then
      demonstrate, qualitatively as well as quantitatively, the ability of their
      approach to achieve more accurate and better localized results over bicubic
      interpolation as well as a related state-of-the-art approach. The authors also
      show results on some datasets with tumor, to further emphasize the clinical
      importance of their method. CONCLUSIONS: The authors have proposed to improve the
      superior-inferior resolution of 4D-CT by estimating intermediate slices. The
      authors' approach exploits neighboring constraints in the group-sparsity
      framework, toward the goal of achieving better localization and noise robustness.
      The authors' results are encouraging, and positively demonstrate the role of
      group-sparsity for 4D-CT resolution enhancement.

PMID- 24320504
TI  - Automated evaluation of setup errors in carbon ion therapy using PET: feasibility
      study.
AB  - PURPOSE: To investigate the possibility of detecting patient mispositioning in
      carbon-ion therapy with particle therapy positron emission tomography (PET) in an
      automated image registration based manner. METHODS: Tumors in the head and neck
      (H&N), pelvic, lung, and brain region were investigated. Biologically optimized
      carbon ion treatment plans were created with TRiP98. From these treatment plans,
      the reference beta(+)-activity distributions were calculated using a Monte Carlo
      simulation. Setup errors were simulated by shifting or rotating the computed
      tomography (CT). The expected beta(+) activity was calculated for each plan with
      shifts. Finally, the reference particle therapy PET images were compared to the
      "shifted" beta(+)-activity distribution simulations using the Pearson's
      correlation coefficient (PCC). To account for different PET monitoring options
      the inbeam PET was compared to three different inroom scenarios. Additionally,
      the dosimetric effects of the CT misalignments were investigated. RESULTS: The
      automated PCC detection of patient mispositioning was possible in the
      investigated indications for cranio-caudal shifts of 4 mm and more, except for
      prostate tumors. In the rather homogeneous pelvic region, the generated beta(+)
      activity distribution of the reference and compared PET image were too much
      alike. Thus, setup errors in this region could not be detected. Regarding lung
      lesions the detection strongly depended on the exact tumor location: in the
      center of the lung tumor misalignments could be detected down to 2 mm shifts
      while resolving shifts of tumors close to the thoracic wall was more challenging.
      Rotational shifts in the H&N and lung region of +6 degrees  and more could be
      detected using inroom PET and partly using inbeam PET. Comparing inroom PET to
      inbeam PET no obvious trend was found. However, among the inroom scenarios a
      longer measurement time was found to be advantageous. CONCLUSIONS: This study
      scopes the use of various particle therapy PET verification techniques in four
      indications. The automated detection of patients' setup errors was investigated
      in a broad accumulation of data sets. The evaluation of introduced setup errors
      is performed automatically, which is of utmost importance to introduce highly
      required particle therapy monitoring devices into the clinical routine.

PMID- 24320505
TI  - Experimental validation of the TOPAS Monte Carlo system for passive scattering
      proton therapy.
AB  - PURPOSE: TOPAS (TOol for PArticle Simulation) is a particle simulation code
      recently developed with the specific aim of making Monte Carlo simulations user
      friendly for research and clinical physicists in the particle therapy community.
      The authors present a thorough and extensive experimental validation of Monte
      Carlo simulations performed with TOPAS in a variety of setups relevant for proton
      therapy applications. The set of validation measurements performed in this work
      represents an overall end-to-end testing strategy recommended for all clinical
      centers planning to rely on TOPAS for quality assurance or patient dose
      calculation and, more generally, for all the institutions using passive
      scattering proton therapy systems. METHODS: The authors systematically compared
      TOPAS simulations with measurements that are performed routinely within the
      quality assurance (QA) program in our institution as well as experiments
      specifically designed for this validation study. First, the authors compared
      TOPAS simulations with measurements of depth-dose curves for spread-out Bragg
      peak (SOBP) fields. Second, absolute dosimetry simulations were benchmarked
      against measured machine output factors (OFs). Third, the authors simulated and
      measured 2D dose profiles and analyzed the differences in terms of field flatness
      and symmetry and usable field size. Fourth, the authors designed a simple
      experiment using a half-beam shifter to assess the effects of multiple Coulomb
      scattering, beam divergence, and inverse square attenuation on lateral and
      longitudinal dose profiles measured and simulated in a water phantom. Fifth,
      TOPAS' capabilities to simulate time dependent beam delivery was benchmarked
      against dose rate functions (i.e., dose per unit time vs time) measured at
      different depths inside an SOBP field. Sixth, simulations of the charge deposited
      by protons fully stopping in two different types of multilayer Faraday cups
      (MLFCs) were compared with measurements to benchmark the nuclear interaction
      models used in the simulations. RESULTS: SOBPs' range and modulation width were
      reproduced, on average, with an accuracy of +1, -2 and +/-3 mm, respectively. OF
      simulations reproduced measured data within +/-3%. Simulated 2D dose-profiles
      show field flatness and average field radius within +/-3% of measured profiles.
      The field symmetry resulted, on average in +/-3% agreement with commissioned
      profiles. TOPAS accuracy in reproducing measured dose profiles downstream the
      half beam shifter is better than 2%. Dose rate function simulation reproduced the
      measurements within ~2% showing that the four-dimensional modeling of the
      passively modulation system was implement correctly and millimeter accuracy can
      be achieved in reproducing measured data. For MLFCs simulations, 2% agreement was
      found between TOPAS and both sets of experimental measurements. The overall
      results show that TOPAS simulations are within the clinical accepted tolerances
      for all QA measurements performed at our institution. CONCLUSIONS: Our Monte
      Carlo simulations reproduced accurately the experimental data acquired through
      all the measurements performed in this study. Thus, TOPAS can reliably be applied
      to quality assurance for proton therapy and also as an input for commissioning of
      commercial treatment planning systems. This work also provides the basis for
      routine clinical dose calculations in patients for all passive scattering proton
      therapy centers using TOPAS.

PMID- 24320506
TI  - Multicriteria optimization of the spatial dose distribution.
AB  - PURPOSE: Treatment planning for radiation therapy involves trade-offs with
      respect to different clinical goals. Typically, the dose distribution is
      evaluated based on few statistics and dose-volume histograms. Particularly for
      stereotactic treatments, the spatial dose distribution represents further
      criteria, e.g., when considering the gradient between subregions of volumes of
      interest. The authors have studied how to consider the spatial dose distribution
      using a multicriteria optimization approach. METHODS: The authors have extended a
      stepwise multicriteria optimization approach to include criteria with respect to
      the local dose distribution. Based on a three-dimensional visualization of the
      dose the authors use a software tool allowing interaction with the dose
      distribution to map objectives with respect to its shape to a constrained
      optimization problem. Similarly, conflicting criteria are highlighted and the
      planner decides if and where to relax the shape of the dose distribution.
      RESULTS: To demonstrate the potential of spatial multicriteria optimization, the
      tool was applied to a prostate and meningioma case. For the prostate case, local
      sparing of the rectal wall and shaping of a boost volume are achieved through
      local relaxations and while maintaining the remaining dose distribution. For the
      meningioma, target coverage is improved by compromising low dose conformality
      toward noncritical structures. A comparison of dose-volume histograms illustrates
      the importance of spatial information for achieving the trade-offs. CONCLUSIONS:
      The results show that it is possible to consider the location of conflicting
      criteria during treatment planning. Particularly, it is possible to conserve
      already achieved goals with respect to the dose distribution, to visualize
      potential trade-offs, and to relax constraints locally. Hence, the proposed
      approach facilitates a systematic exploration of the optimal shape of the dose
      distribution.

PMID- 24320507
TI  - Investigation of various energy deposition kernel refinements for the
      convolution/superposition method.
AB  - PURPOSE: Several simplifications used in clinical implementations of the
      convolution/superposition (C/S) method, specifically, density scaling of water
      kernels for heterogeneous media and use of a single polyenergetic kernel, lead to
      dose calculation inaccuracies. Although these weaknesses of the C/S method are
      known, it is not well known which of these simplifications has the largest effect
      on dose calculation accuracy in clinical situations. The purpose of this study
      was to generate and characterize high-resolution, polyenergetic, and material
      specific energy deposition kernels (EDKs), as well as to investigate the
      dosimetric impact of implementing spatially variant polyenergetic and material
      specific kernels in a collapsed cone C/S algorithm. METHODS: High-resolution,
      monoenergetic water EDKs and various material-specific EDKs were simulated using
      the EGSnrc Monte Carlo code. Polyenergetic kernels, reflecting the primary
      spectrum of a clinical 6 MV photon beam at different locations in a water
      phantom, were calculated for different depths, field sizes, and off-axis
      distances. To investigate the dosimetric impact of implementing spatially variant
      polyenergetic kernels, depth dose curves in water were calculated using two
      different implementations of the collapsed cone C/S method. The first method uses
      a single polyenergetic kernel, while the second method fully takes into account
      spectral changes in the convolution calculation. To investigate the dosimetric
      impact of implementing material-specific kernels, depth dose curves were
      calculated for a simplified titanium implant geometry using both a traditional
      C/S implementation that performs density scaling of water kernels and a novel
      implementation using material-specific kernels. RESULTS: For our high-resolution
      kernels, we found good agreement with the Mackie et al. kernels, with some
      differences near the interaction site for low photon energies (<500 keV). For our
      spatially variant polyenergetic kernels, we found that depth was the most
      dominant factor affecting the pattern of energy deposition; however, the effects
      of field size and off-axis distance were not negligible. For the material
      specific kernels, we found that as the density of the material increased, more
      energy was deposited laterally by charged particles, as opposed to in the forward
      direction. Thus, density scaling of water kernels becomes a worse approximation
      as the density and the effective atomic number of the material differ more from
      water. Implementation of spatially variant, polyenergetic kernels increased the
      percent depth dose value at 25 cm depth by 2.1%-5.8% depending on the field size,
      while implementation of titanium kernels gave 4.9% higher dose upstream of the
      metal cavity (i.e., higher backscatter dose) and 8.2% lower dose downstream of
      the cavity. CONCLUSIONS: Of the various kernel refinements investigated,
      inclusion of depth-dependent and metal-specific kernels into the C/S method has
      the greatest potential to improve dose calculation accuracy. Implementation of
      spatially variant polyenergetic kernels resulted in a harder depth dose curve and
      thus has the potential to affect beam modeling parameters obtained in the
      commissioning process. For metal implants, the C/S algorithms generally
      underestimate the dose upstream and overestimate the dose downstream of the
      implant. Implementation of a metal-specific kernel mitigated both of these
      errors.

PMID- 24320508
TI  - Monte Carlo calculations for reference dosimetry of electron beams with the PTW
      Roos and NE2571 ion chambers.
AB  - PURPOSE: To investigate recommendations for reference dosimetry of electron beams
      and gradient effects for the NE2571 chamber and to provide beam quality
      conversion factors using Monte Carlo simulations of the PTW Roos and NE2571 ion
      chambers. METHODS: The EGSnrc code system is used to calculate the absorbed dose
      to-water and the dose to the gas in fully modeled ion chambers as a function of
      depth in water. Electron beams are modeled using realistic accelerator
      simulations as well as beams modeled as collimated point sources from realistic
      electron beam spectra or monoenergetic electrons. Beam quality conversion factors
      are calculated with ratios of the doses to water and to the air in the ion
      chamber in electron beams and a cobalt-60 reference field. The overall ion
      chamber correction factor is studied using calculations of water-to-air stopping
      power ratios. RESULTS: The use of an effective point of measurement shift of 1.55
      mm from the front face of the PTW Roos chamber, which places the point of
      measurement inside the chamber cavity, minimizes the difference between R50, the
      beam quality specifier, calculated from chamber simulations compared to that
      obtained using depth-dose calculations in water. A similar shift minimizes the
      variation of the overall ion chamber correction factor with depth to the
      practical range and reduces the root-mean-square deviation of a fit to calculated
      beam quality conversion factors at the reference depth as a function of R50.
      Similarly, an upstream shift of 0.34 rcav allows a more accurate determination of
      R50 from NE2571 chamber calculations and reduces the variation of the overall ion
      chamber correction factor with depth. The determination of the gradient
      correction using a shift of 0.22 rcav optimizes the root-mean-square deviation of
      a fit to calculated beam quality conversion factors if all beams investigated are
      considered. However, if only clinical beams are considered, a good fit to results
      for beam quality conversion factors is obtained without explicitly correcting for
      gradient effects. The inadequacy of R50 to uniquely specify beam quality for the
      accurate selection of kQ factors is discussed. Systematic uncertainties in beam
      quality conversion factors are analyzed for the NE2571 chamber and amount to
      between 0.4% and 1.2% depending on assumptions used. CONCLUSIONS: The calculated
      beam quality conversion factors for the PTW Roos chamber obtained here are in
      good agreement with literature data. These results characterize the use of an
      NE2571 ion chamber for reference dosimetry of electron beams even in low-energy
      beams.

PMID- 24320509
TI  - Physiologically guided approach to characterizing respiratory motion.
AB  - PURPOSE: To characterize radiation therapy patient breathing patterns based on
      measured external surrogate information. METHODS: Breathing surrogate data were
      collected during 4DCT from a cohort of 50 patients including 28 patients with
      lung cancer and 22 patients without lung cancer. A spirometer and an abdominal
      pneumatic bellows were used as the surrogates. The relationship between these
      measurements was assumed to be linear within a small phase difference. The
      signals were correlated and drift corrected using a previously published method
      to convert the signal into tidal volume. The airflow was calculated with a first
      order time derivative of the tidal volume using a window centered on the point of
      interest and with a window length equal to the CT gantry rotation period. The
      airflow was compared against the tidal volume to create ellipsoidal patterns that
      were binned into 25 ml * 25 ml/s bins to determine the relative amount of time
      spent in each bin. To calculate the variability of the maximum inhalation tidal
      volume within a free-breathing scan timeframe, a metric based on percentile
      volume ratios was defined. The free breathing variability metric (kappa) was
      defined as the ratio between extreme inhalation tidal volumes (defined as >93
      tidal volume percentile of the measured tidal volume) and normal inhalation tidal
      volume (defined as >80 tidal volume percentile of the measured tidal volume).
      RESULTS: There were three observed types of volume-flow curves, labeled Types 1,
      2, and 3. Type 1 patients spent a greater duration of time during exhalation with
      kappa = 1.37 +/- 0.11. Type 2 patients had equal time duration spent during
      inhalation and exhalation with kappa = 1.28 +/- 0.09. The differences between the
      mean peak exhalation to peak inhalation tidal volume, breathing period, and the
      85th tidal volume percentile for Type 1 and Type 2 patients were statistically
      significant at the 2% significance level. The difference between kappa and the
      98th tidal volume percentile for Type 1 and Type 2 patients was found to be
      statistically significant at the 1% significance level. Three patients did not
      display a breathing stability curve that could be classified as Type 1 or Type 2
      due to chaotic breathing patterns. These patients were classified as Type 3
      patients. CONCLUSIONS: Based on an observed volume-flow curve pattern, the cohort
      of 50 patients was divided into three categories called Type 1, Type 2, and Type
      3. There were statistically significant differences in breathing characteristics
      between Type 1 and Type 2 patients. The use of volume-flow curves to classify
      patients has been demonstrated as a physiological characterization metric that
      has the potential to optimize gating windows in radiation therapy.

PMID- 24320510
TI  - Measuring uncertainty in dose delivered to the cochlea due to setup error during
      external beam treatment of patients with cancer of the head and neck.
AB  - PURPOSE: To use Cone Beam CT scans obtained just prior to treatments of head and
      neck cancer patients to measure the setup error and cumulative dose uncertainty
      of the cochlea. METHODS: Data from 10 head and neck patients with 10 planning CTs
      and 52 Cone Beam CTs taken at time of treatment were used in this study. Patients
      were treated with conventional fractionation using an IMRT dose painting
      technique, most with 33 fractions. Weekly radiographic imaging was used to
      correct the patient setup. The authors used rigid registration of the planning CT
      and Cone Beam CT scans to find the translational and rotational setup errors, and
      the spatial setup errors of the cochlea. The planning CT was rotated and
      translated such that the cochlea positions match those seen in the cone beam
      scans, cochlea doses were recalculated and fractional doses accumulated.
      Uncertainties in the positions and cumulative doses of the cochlea were
      calculated with and without setup adjustments from radiographic imaging. RESULTS:
      The mean setup error of the cochlea was 0.04 +/- 0.33 or 0.06 +/- 0.43 cm for RL,
      0.09 +/- 0.27 or 0.07 +/- 0.48 cm for AP, and 0.00 +/- 0.21 or -0.24 +/- 0.45 cm
      for SI with and without radiographic imaging, respectively. Setup with
      radiographic imaging reduced the standard deviation of the setup error by roughly
      1-2 mm. The uncertainty of the cochlea dose depends on the treatment plan and the
      relative positions of the cochlea and target volumes. Combining results for the
      left and right cochlea, the authors found the accumulated uncertainty of the
      cochlea dose per fraction was 4.82 (0.39-16.8) cGy, or 10.1 (0.8-32.4) cGy, with
      and without radiographic imaging, respectively; the percentage uncertainties
      relative to the planned doses were 4.32% (0.28%-9.06%) and 10.2% (0.7%-63.6%),
      respectively. CONCLUSIONS: Patient setup error introduces uncertainty in the
      position of the cochlea during radiation treatment. With the assistance of
      radiographic imaging during setup, the standard deviation of setup error reduced
      by 31%, 42%, and 54% in RL, AP, and SI direction, respectively, and consequently,
      the uncertainty of the mean dose to cochlea reduced more than 50%. The authors
      estimate that the effects of these uncertainties on the probability of hearing
      loss for an individual patient could be as large as 10%.

PMID- 24320511
TI  - A comprehensive investigation of the accuracy and reproducibility of a
      multitarget single isocenter VMAT radiosurgery technique.
AB  - PURPOSE: Recent trends in stereotactic radiosurgery use multifocal volumetric
      modulated arc therapy (VMAT) plans to simultaneously treat several distinct
      targets. Conventional verification often involves low resolution measurements in
      a single plane, a cylinder, or intersecting planes of diodes or ion chambers.
      This work presents an investigation into the consistency and reproducibility of
      this new treatment technique using a comprehensive commissioned high-resolution
      3D dosimetry system (PRESAGE((r))/Optical-CT). METHODS: A complex VMAT plan
      consisting of a single isocenter but five separate targets was created in Eclipse
      for a head phantom containing a cylindrical PRESAGE((r)) dosimetry insert of 11
      cm diameter and height. The plan contained five VMAT arcs delivering target doses
      from 12 to 20 Gy. The treatment was delivered to four dosimeters positioned in
      the head phantom and repeated four times, yielding four separate 3D dosimetry
      verifications. Each delivery was completely independent and was given after image
      guided radiation therapy (IGRT) positioning using Brainlab ExacTrac and cone beam
      computed tomography. A final delivery was given to a modified insert containing a
      pin-point ion chamber enabling calibration of PRESAGE((r)) 3D data to dose.
      Dosimetric data were read out in an optical-CT scanner. Consistency and
      reproducibility of the treatment technique (including IGRT setup) was
      investigated by comparing the dose distributions in the four inserts, and with
      the predicted treatment planning system distribution. RESULTS: Dose distributions
      from the four dosimeters were registered and analyzed to determine the mean and
      standard deviation at all points throughout the dosimeters. A dose standard
      deviation of <3% was found from dosimeter to dosimeter. Global 3D gamma maps show
      that the predicted and measured dose matched well [3D gamma passing rate was
      98.0% (3%, 2 mm)]. CONCLUSIONS: The deliveries of the irradiation were found to
      be consistent and matched the treatment plan, demonstrating high accuracy and
      reproducibility of both the treatment machine and the IGRT procedure. The
      complexity of the treatment (multiple arcs) and dosimetry (multiple strong
      gradients) pose a substantial challenge for comprehensive verification. 3D
      dosimetry can be uniquely effective in this scenario.

PMID- 24320512
TI  - Texture analysis improves level set segmentation of the anterior abdominal wall.
AB  - PURPOSE: The treatment of ventral hernias (VH) has been a challenging problem for
      medical care. Repair of these hernias is fraught with failure; recurrence rates
      ranging from 24% to 43% have been reported, even with the use of biocompatible
      mesh. Currently, computed tomography (CT) is used to guide intervention through
      expert, but qualitative, clinical judgments, notably, quantitative metrics based
      on image-processing are not used. The authors propose that image segmentation
      methods to capture the three-dimensional structure of the abdominal wall and its
      abnormalities will provide a foundation on which to measure geometric properties
      of hernias and surrounding tissues and, therefore, to optimize intervention.
      METHODS: In this study with 20 clinically acquired CT scans on postoperative
      patients, the authors demonstrated a novel approach to geometric classification
      of the abdominal. The authors' approach uses a texture analysis based on Gabor
      filters to extract feature vectors and follows a fuzzy c-means clustering method
      to estimate voxelwise probability memberships for eight clusters. The memberships
      estimated from the texture analysis are helpful to identify anatomical structures
      with inhomogeneous intensities. The membership was used to guide the level set
      evolution, as well as to derive an initial start close to the abdominal wall.
      RESULTS: Segmentation results on abdominal walls were both quantitatively and
      qualitatively validated with surface errors based on manually labeled ground
      truth. Using texture, mean surface errors for the outer surface of the abdominal
      wall were less than 2 mm, with 91% of the outer surface less than 5 mm away from
      the manual tracings; errors were significantly greater (2-5 mm) for methods that
      did not use the texture. CONCLUSIONS: The authors' approach establishes a
      baseline for characterizing the abdominal wall for improving VH care. Inherent
      texture patterns in CT scans are helpful to the tissue classification, and
      texture analysis can improve the level set segmentation around the abdominal
      region.

PMID- 24320513
TI  - Constancy of built-in luminance meter measurements in diagnostic displays.
AB  - PURPOSE: Liquid crystal displays used to interpret medical images are often
      equipped with built-in luminance meters to evaluate luminance response and
      Grayscale Standard Display Function conformance. This work evaluates agreement
      between luminance reported by the built-in meters and external measurements.
      METHODS: The white level luminance was measured using a built-in meter and an
      external meter for 93 primary review workstations (Models MFGD 3420 and MDCG 3120
      CB) with between 117 and 49,336 backlight hours (BLH). Measured luminance values
      were compared via t-test for displays with less than 25,000 BLH and those with
      more than 25,000 BLH. Bias between meters was also evaluated. Changes in
      luminance uniformity with increasing backlight hours were explored by determining
      the maximum luminance deviation (MLD) for subsets of these displays with less
      than 800 BLH and greater than 35,000 BLH. RESULTS: The mean difference between
      built-in and external luminance measurements was 5.84% and 38.92% for displays
      with less than 25,000 and greater than 25,000 BLH, respectively, with a
      statistically significant difference in the means (p < 0.001). For displays with
      low BLH, a statistically significant bias was observed (p < 0.001) between built
      in and external measurements. A high degree of correlation was observed between
      measurements made with two separate external meters (r = 0.999). The mean MLD was
      9.5% and 11.2% for MDCG 3120-CB displays with less than 800 and greater than
      35,000 BLH, respectively. The difference in the mean values was not statistically
      significant (p < 0.001). CONCLUSIONS: Disagreement between the white level
      luminance measured using the built-in and external meter increased with BLH.
      Consequently, reliance on values reported by the built-in luminance meter may
      result in a reduction in image contrast with time. Recommendations have been
      proposed regarding luminance response testing and corrective action for failing
      displays.

PMID- 24320514
TI  - Pulmonary lobe segmentation based on ridge surface sampling and shape model
      fitting.
AB  - PURPOSE: Performing lobe-based quantitative analysis of the lung in computed
      tomography (CT) scans can assist in efforts to better characterize complex
      diseases such as chronic obstructive pulmonary disease (COPD). While airways and
      vessels can help to indicate the location of lobe boundaries, segmentations of
      these structures are not always available, so methods to define the lobes in the
      absence of these structures are desirable. METHODS: The authors present a fully
      automatic lung lobe segmentation algorithm that is effective in volumetric
      inspiratory and expiratory computed tomography (CT) datasets. The authors rely on
      ridge surface image features indicating fissure locations and a novel approach to
      modeling shape variation in the surfaces defining the lobe boundaries. The
      authors employ a particle system that efficiently samples ridge surfaces in the
      image domain and provides a set of candidate fissure locations based on the
      Hessian matrix. Following this, lobe boundary shape models generated from
      principal component analysis (PCA) are fit to the particles data to discriminate
      between fissure and nonfissure candidates. The resulting set of particle points
      are used to fit thin plate spline (TPS) interpolating surfaces to form the final
      boundaries between the lung lobes. RESULTS: The authors tested algorithm
      performance on 50 inspiratory and 50 expiratory CT scans taken from the COPDGene
      study. Results indicate that the authors' algorithm performs comparably to
      pulmonologist-generated lung lobe segmentations and can produce good results in
      cases with accessory fissures, incomplete fissures, advanced emphysema, and low
      dose acquisition protocols. Dice scores indicate that only 29 out of 500 (5.85%)
      lobes showed Dice scores lower than 0.9. Two different approaches for evaluating
      lobe boundary surface discrepancies were applied and indicate that algorithm
      boundary identification is most accurate in the vicinity of fissures detectable
      on CT. CONCLUSIONS: The proposed algorithm is effective for lung lobe
      segmentation in absence of auxiliary structures such as vessels and airways. The
      most challenging cases are those with mostly incomplete, absent, or near-absent
      fissures and in cases with poorly revealed fissures due to high image noise.
      However, the authors observe good performance even in the majority of these
      cases.

PMID- 24320515
TI  - Automated registration of multispectral MR vessel wall images of the carotid
      artery.
AB  - PURPOSE: Atherosclerosis is the primary cause of heart disease and stroke. The
      detailed assessment of atherosclerosis of the carotid artery requires high
      resolution imaging of the vessel wall using multiple MR sequences with different
      contrast weightings. These images allow manual or automated classification of
      plaque components inside the vessel wall. Automated classification requires all
      sequences to be in alignment, which is hampered by patient motion. In clinical
      practice, correction of this motion is performed manually. Previous studies
      applied automated image registration to correct for motion using only
      nondeformable transformation models and did not perform a detailed quantitative
      validation. The purpose of this study is to develop an automated accurate 3D
      registration method, and to extensively validate this method on a large set of
      patient data. In addition, the authors quantified patient motion during scanning
      to investigate the need for correction. METHODS: MR imaging studies (1.5T,
      dedicated carotid surface coil, Philips) from 55 TIA/stroke patients with
      ipsilateral <70% carotid artery stenosis were randomly selected from a larger
      cohort. Five MR pulse sequences were acquired around the carotid bifurcation,
      each containing nine transverse slices: T1-weighted turbo field echo, time of
      flight, T2-weighted turbo spin-echo, and pre- and postcontrast T1-weighted turbo
      spin-echo images (T1W TSE). The images were manually segmented by delineating the
      lumen contour in each vessel wall sequence and were manually aligned by applying
      throughplane and inplane translations to the images. To find the optimal
      automatic image registration method, different masks, choice of the fixed image,
      different types of the mutual information image similarity metric, and
      transformation models including 3D deformable transformation models, were
      evaluated. Evaluation of the automatic registration results was performed by
      comparing the lumen segmentations of the fixed image and moving image after
      registration. RESULTS: The average required manual translation per image slice
      was 1.33 mm. Translations were larger as the patient was longer inside the
      scanner. Manual alignment took 187.5 s per patient resulting in a mean surface
      distance of 0.271 +/- 0.127 mm. After minimal user interaction to generate the
      mask in the fixed image, the remaining sequences are automatically registered
      with a computation time of 52.0 s per patient. The optimal registration strategy
      used a circular mask with a diameter of 10 mm, a 3D B-spline transformation model
      with a control point spacing of 15 mm, mutual information as image similarity
      metric, and the precontrast T1W TSE as fixed image. A mean surface distance of
      0.288 +/- 0.128 mm was obtained with these settings, which is very close to the
      accuracy of the manual alignment procedure. The exact registration parameters and
      software were made publicly available. CONCLUSIONS: An automated registration
      method was developed and optimized, only needing two mouse clicks to mark the
      start and end point of the artery. Validation on a large group of patients showed
      that automated image registration has similar accuracy as the manual alignment
      procedure, substantially reducing the amount of user interactions needed, and is
      multiple times faster. In conclusion, the authors believe that the proposed
      automated method can replace the current manual procedure, thereby reducing the
      time to analyze the images.

PMID- 24320516
TI  - The effects of gantry tilt on breast dose and image noise in cardiac CT.
AB  - PURPOSE: This study investigated the effects of tilted-gantry acquisition on
      image noise and glandular breast dose in females during cardiac computed
      tomography (CT) scans. Reducing the dose to glandular breast tissue is important
      due to its high radiosensitivity and limited diagnostic significance in cardiac
      CT scans. METHODS: Tilted-gantry acquisition was investigated through computer
      simulations and experimental measurements. Upon IRB approval, eight voxelized
      phantoms were constructed from previously acquired cardiac CT datasets. Monte
      Carlo simulations quantified the dose deposited in glandular breast tissue over a
      range of tilt angles. The effects of tilted-gantry acquisition on breast dose
      were measured on a clinical CT scanner (CT750HD, GE Healthcare) using an
      anthropomorphic phantom with MOSFET dosimeters in the breast regions. In both
      simulations and experiments, scans were performed at gantry tilt angles of 0
      degrees -30 degrees , in 5 degrees  increments. The percent change in breast dose
      was calculated relative to the nontilted scan for all tilt angles. The percent
      change in noise standard deviation due to gantry tilt was calculated in all
      reconstructed simulated and experimental images. RESULTS: Tilting the gantry
      reduced the breast dose in all simulated and experimental phantoms, with
      generally greater dose reduction at increased gantry tilts. For example, at 30
      degrees  gantry tilt, the dosimeters located in the superior, middle, and
      inferior breast regions measured dose reductions of 74%, 61%, and 9%,
      respectively. The simulations estimated 0%-30% total breast dose reduction across
      the eight phantoms and range of tilt angles. However, tilted-gantry acquisition
      also increased the noise standard deviation in the simulated phantoms by 2%-50%
      due to increased pathlength through the iodine-filled heart. The experimental
      phantom, which did not contain iodine in the blood, demonstrated decreased breast
      dose and decreased noise at all gantry tilt angles. CONCLUSIONS: Tilting the
      gantry reduced the dose to the breast, while also increasing noise standard
      deviation. Overall, the noise increase outweighed the dose reduction for the
      eight voxelized phantoms, suggesting that tilted gantry acquisition may not be
      beneficial for reducing breast dose while maintaining image quality.

PMID- 24320517
TI  - Individually optimized uniform contrast enhancement in CT angiography for the
      diagnosis of pulmonary thromboembolic disease--a simulation study.
AB  - PURPOSE: To improve the diagnostic quality of CT pulmonary angiography (CTPA) by
      individually optimizing a biphasic contrast injection function to achieve
      targeted uniform contrast enhancement. To compare the results against a
      previously reported discrete Fourier transform (DFT) approach. METHODS: This
      simulation study used the CTPA datasets of 27 consecutive patients with pulmonary
      thromboembolic disease (PE). An optimization approach was developed consisting of
      (1) computation of the impulse enhancement function (IEF) based on a test bolus
      scan, and (2) optimization of a biphasic contrast injection function using the
      IEF in order to achieve targeted uniform enhancement. The injection rates and
      durations of a biphasic contrast injection function are optimized by minimizing
      the difference between the resulting contrast enhancement curve and the targeted
      uniform enhancement curve, while conforming to the clinical constraints of
      injection rate and total contrast volume. The total contrast volume was limited
      first to the clinical standard of 65 ml, and then to the same amount used in the
      DFT approach for comparison. The optimization approach and the DFT approach were
      compared in terms of the root mean square error (RMSE) and total contrast volume
      used. RESULTS: When the total contrast volume was limited to 65 ml, the
      optimization approach produced significantly better contrast enhancement (closer
      to the targeted uniform contrast enhancement) than the DFT approach (RMSE 17 HU
      vs 56 HU, p < 0.00001). On average, the optimization approach used 63 ml
      contrast, while the DFT approach used 50 ml with four patients exceeding 65 ml.
      When equivalent total contrast volume was used for individual patient, the
      optimization approach still generated significantly better contrast enhancement
      (RMSE 44 HU vs 56 HU, p < 0.01). Constraints for the injection function could be
      easily accommodated into the optimization process when searching for the optimal
      biphasic injection function. CONCLUSIONS: The optimization approach generated
      individually optimized biphasic injection functions yielding significantly better
      contrast enhancement compared to the DFT approach. This new approach has the
      potential to improve the diagnostic quality of CTPA for PE.

PMID- 24320518
TI  - Distance-preserving rigidity penalty on deformable image registration of multiple
      skeletal components in the neck.
AB  - PURPOSE: This study aims at developing and testing a novel rigidity penalty
      suitable for the deformable registration of tightly located skeletal components
      in the head and neck from planning computed tomography (CT) and daily cone-beam
      CT (CBCT) scans of patients undergoing radiotherapy. METHODS: The proposed
      rigidity penalty is designed to preserve intervoxel distances within each bony
      structure. This penalty was tested in the intensity-based B-spline deformable
      registration of five cervical vertebral bodies (C1-C5). The displacement vector
      fields (DVFs) from the registrations were compared to the DVFs generated by using
      rigid body motions of the cervical vertebrae, measured by the surface
      registration of vertebrae delineated on CT and CBCT images. Twenty five pairs of
      planning CT (reference) and treatment CBCTs (target) from five patients were
      aligned without and with the penalty. An existing penalty based on the
      orthonormality of the deformation gradient tensor was also tested and the effects
      of the penalties compared. RESULTS: The mean magnitude of the maximum
      registration error with the proposed distance-preserving penalty was (0.86, 1.12,
      1.33) mm compared to (2.11, 2.49, 2.46) without penalty and (1.53, 1.64, 1.64)
      with the existing orthonormality-based penalty. The improvement in the accuracy
      of the deformable image registration was also verified by comparing the
      Procrustes distance between the DVFs. With the proposed penalty, the average
      distance was 0.11 (sigma 0.03 mm) which is smaller than 0.53 (0.1 mm) without
      penalty and 0.28 (0.04 mm) with the orthonormality-based penalty. CONCLUSIONS:
      The accuracy of aligning multiple bony elements was improved by using the
      proposed distance-preserving rigidity penalty. The voxel-based statistical
      analysis of the registration error shows that the proposed penalty improved the
      integrity of the DVFs within the vertebral bodies.

PMID- 24320519
TI  - Novel multimodality segmentation using level sets and Jensen-Renyi divergence.
AB  - PURPOSE: Positron emission tomography (PET) is playing an increasing role in
      radiotherapy treatment planning. However, despite progress, robust algorithms for
      PET and multimodal image segmentation are still lacking, especially if the
      algorithm were extended to image-guided and adaptive radiotherapy (IGART). This
      work presents a novel multimodality segmentation algorithm using the Jensen-Renyi
      divergence (JRD) to evolve the geometric level set contour. The algorithm offers
      improved noise tolerance which is particularly applicable to segmentation of
      regions found in PET and cone-beam computed tomography. METHODS: A steepest
      gradient ascent optimization method is used in conjunction with the JRD and a
      level set active contour to iteratively evolve a contour to partition an image
      based on statistical divergence of the intensity histograms. The algorithm is
      evaluated using PET scans of pharyngolaryngeal squamous cell carcinoma with the
      corresponding histological reference. The multimodality extension of the
      algorithm is evaluated using 22 PET/CT scans of patients with lung carcinoma and
      a physical phantom scanned under varying image quality conditions. RESULTS: The
      average concordance index (CI) of the JRD segmentation of the PET images was 0.56
      with an average classification error of 65%. The segmentation of the lung
      carcinoma images had a maximum diameter relative error of 63%, 19.5%, and 14.8%
      when using CT, PET, and combined PET/CT images, respectively. The estimated
      maximal diameters of the gross tumor volume (GTV) showed a high correlation with
      the macroscopically determined maximal diameters, with a R(2) value of 0.85 and
      0.88 using the PET and PET/CT images, respectively. Results from the physical
      phantom show that the JRD is more robust to image noise compared to mutual
      information and region growing. CONCLUSIONS: The JRD has shown improved noise
      tolerance compared to mutual information for the purpose of PET image
      segmentation. Presented is a flexible framework for multimodal image segmentation
      that can incorporate a large number of inputs efficiently for IGART.

PMID- 24320520
TI  - Compensator models for fluence field modulated computed tomography.
AB  - PURPOSE: Fluence field modulated computed tomography (FFMCT) presents a novel
      approach for acquiring CT images, whereby a patient model guides dynamically
      changing fluence patterns in an attempt to achieve task-based, user-prescribed,
      regional variations in image quality, while also controlling dose to the patient.
      This work aims to compare the relative effectiveness of FFMCT applied to
      different thoracic imaging tasks (routine diagnostic CT, lung cancer screening,
      and cardiac CT) when the modulator is subject to limiting constraints, such as
      might be present in realistic implementations. METHODS: An image quality plan was
      defined for a simulated anthropomorphic chest slice, including regions of high
      and low image quality, for each of the thoracic imaging tasks. Modulated fluence
      patterns were generated using a simulated annealing optimization script, which
      attempts to achieve the image quality plan under a global dosimetric constraint.
      Optimization was repeated under different types of modulation constraints (e.g.,
      fixed or gantry angle dependent patterns, continuous or comprised of discrete
      apertures) with the most limiting case being a fixed conventional bowtie filter.
      For each thoracic imaging task, an image quality map (IQMsd) representing the
      regionally varying standard deviation is predicted for each modulation method and
      compared to the prescribed image quality plan as well as against results from
      uniform fluence fields. Relative integral dose measures were also compared.
      RESULTS: Each IQMsd resulting from FFMCT showed improved agreement with planned
      objectives compared to those from uniform fluence fields for all cases.
      Dynamically changing modulation patterns yielded better uniformity, improved
      image quality, and lower dose compared to fixed filter patterns with optimized
      tube current. For the latter fixed filter cases, the optimal choice of tube
      current modulation was found to depend heavily on the task. Average integral dose
      reduction compared to a uniform fluence field ranged from 10% using a bowtie
      filter to 40% or greater using an idealized modulator. CONCLUSIONS: The results
      support that FFMCT may achieve regionally varying image quality distributions in
      good agreement with user-prescribed values, while limiting dose. The imposition
      of constraints inhibits dose reduction capacity and agreement with image quality
      plans but still yields significant improvement over what is afforded by
      conventional dose minimization techniques. These results suggest that FFMCT can
      be implemented effectively even when the modulator has limited modulation
      capabilities.

PMID- 24320521
TI  - Generation of virtual monochromatic CBCT from dual kV/MV beam projections.
AB  - PURPOSE: To develop a novel on-board imaging technique which allows generation of
      virtual monochromatic (VM) cone-beam CT (CBCT) with a selected energy from
      combined kilovoltage (kV)/megavoltage (MV) beam projections. METHODS: With the
      current orthogonal kV/MV imaging hardware equipped in modern linear accelerators,
      both MV projections (from gantry angle of 0 degrees -100 degrees ) and kV
      projections (90 degrees -200 degrees ) were acquired as gantry rotated a total of
      110 degrees . A selected range of overlap projections between 90 degrees  to 100
      degrees  were then decomposed into two material projections using experimentally
      determined parameters from orthogonally stacked aluminum and acrylic step-wedges.
      Given attenuation coefficients of aluminum and acrylic at a predetermined energy,
      one set of VM projections could be synthesized from two corresponding sets of
      decomposed projections. Two linear functions were generated using projection
      information at overlap angles to convert kV and MV projections at nonoverlap
      angles to approximate VM projections for CBCT reconstruction. The contrast-to
      noise ratios (CNRs) were calculated for different inserts in VM CBCTs of a
      CatPhan phantom with various selected energies and compared with those in kV and
      MV CBCTs. The effect of overlap projection number on CNR was evaluated.
      Additionally, the effect of beam orientation was studied by scanning the CatPhan
      sandwiched with two 5 cm solid-water phantoms on both lateral sides and an
      electronic density phantom with two metal bolt inserts. RESULTS: Proper selection
      of VM energy [30 and 40 keV for low-density polyethylene (LDPE),
      polymethylpentene, 2 MeV for Delrin] provided comparable or even better CNR
      results as compared with kV or MV CBCT. An increased number of overlap kV and MV
      projection demonstrated only marginal improvements of CNR for different inserts
      (with the exception of LDPE) and therefore one projection overlap was found to be
      sufficient for the CatPhan study. It was also evident that the optimal CBCT image
      quality was achieved when MV beams penetrated through the heavy attenuation
      direction of the object. CONCLUSIONS: A novel technique was developed to generate
      VM CBCTs from kV/MV projections. This technique has the potential to improve CNR
      at selected VM energies and to suppress artifacts at appropriate beam
      orientations.

PMID- 24320522
TI  - Interactive initialization of 2D/3D rigid registration.
AB  - PURPOSE: Registration is one of the key technical components in an image-guided
      navigation system. A large number of 2D/3D registration algorithms have been
      previously proposed, but have not been able to transition into clinical practice.
      The authors identify the primary reason for the lack of adoption with the
      prerequisite for a sufficiently accurate initial transformation, mean target
      registration error of about 10 mm or less. In this paper, the authors present two
      interactive initialization approaches that provide the desired accuracy for x
      ray/MR and x-ray/CT registration in the operating room setting. METHODS: The
      authors have developed two interactive registration methods based on visual
      alignment of a preoperative image, MR, or CT to intraoperative x-rays. In the
      first approach, the operator uses a gesture based interface to align a volume
      rendering of the preoperative image to multiple x-rays. The second approach uses
      a tracked tool available as part of a navigation system. Preoperatively, a
      virtual replica of the tool is positioned next to the anatomical structures
      visible in the volumetric data. Intraoperatively, the physical tool is positioned
      in a similar manner and subsequently used to align a volume rendering to the x
      ray images using an augmented reality (AR) approach. Both methods were assessed
      using three publicly available reference data sets for 2D/3D registration
      evaluation. RESULTS: In the authors' experiments, the authors show that for x
      ray/MR registration, the gesture based method resulted in a mean target
      registration error (mTRE) of 9.3 +/- 5.0 mm with an average interaction time of
      146.3 +/- 73.0 s, and the AR-based method had mTREs of 7.2 +/- 3.2 mm with
      interaction times of 44 +/- 32 s. For x-ray/CT registration, the gesture based
      method resulted in a mTRE of 7.4 +/- 5.0 mm with an average interaction time of
      132.1 +/- 66.4 s, and the AR-based method had mTREs of 8.3 +/- 5.0 mm with
      interaction times of 58 +/- 52 s. CONCLUSIONS: Based on the authors' evaluation,
      the authors conclude that the registration approaches are sufficiently accurate
      for initializing 2D/3D registration in the OR setting, both when a tracking
      system is not in use (gesture based approach), and when a tracking system is
      already in use (AR based approach).

PMID- 24320523
TI  - Estimating nonrigid motion from inconsistent intensity with robust shape
      features.
AB  - PURPOSE: To develop a nonrigid motion estimation method that is robust to
      heterogeneous intensity inconsistencies amongst the image pairs or image
      sequence. METHODS: Intensity and contrast variations, as in dynamic contrast
      enhanced magnetic resonance imaging, present a considerable challenge to
      registration methods based on general discrepancy metrics. In this study, the
      authors propose and validate a novel method that is robust to such variations by
      utilizing shape features. The geometry of interest (GOI) is represented with a
      flexible zero level set, segmented via well-behaved regularized optimization. The
      optimization energy drives the zero level set to high image gradient regions, and
      regularizes it with area and curvature priors. The resulting shape exhibits high
      consistency even in the presence of intensity or contrast variations.
      Subsequently, a multiscale nonrigid registration is performed to seek a regular
      deformation field that minimizes shape discrepancy in the vicinity of GOIs.
      RESULTS: To establish the working principle, realistic 2D and 3D images were
      subject to simulated nonrigid motion and synthetic intensity variations, so as to
      enable quantitative evaluation of registration performance. The proposed method
      was benchmarked against three alternative registration approaches, specifically,
      optical flow, B-spline based mutual information, and multimodality demons. When
      intensity consistency was satisfied, all methods had comparable registration
      accuracy for the GOIs. When intensities among registration pairs were
      inconsistent, however, the proposed method yielded pronounced improvement in
      registration accuracy, with an approximate fivefold reduction in mean absolute
      error (MAE = 2.25 mm, SD = 0.98 mm), compared to optical flow (MAE = 9.23 mm, SD
      = 5.36 mm), B-spline based mutual information (MAE = 9.57 mm, SD = 8.74 mm) and
      mutimodality demons (MAE = 10.07 mm, SD = 4.03 mm). Applying the proposed method
      on a real MR image sequence also provided qualitatively appealing results,
      demonstrating good feasibility and applicability of the proposed method.
      CONCLUSIONS: The authors have developed a novel method to estimate the nonrigid
      motion of GOIs in the presence of spatial intensity and contrast variations,
      taking advantage of robust shape features. Quantitative analysis and qualitative
      evaluation demonstrated good promise of the proposed method. Further clinical
      assessment and validation is being performed.

PMID- 24320524
TI  - Simultaneous reduction of radiation dose and scatter for CBCT by using
      collimators.
AB  - PURPOSE: On-board cone-beam CT (CBCT) imaging has been widely available in
      radiotherapy clinic for target localization. However, the extra radiation dose
      from CBCT is always a concern for its frequent use. Additionally, the relatively
      large scatter in CBCT often degrades the image quality. By using collimators,
      some of the X-rays can be stopped from reaching the patient and the detectors,
      hence both the scatter and the patient doses are simultaneously reduced. The
      authors show in this work that the collimated CBCT data can be reconstructed
      without any noticeable artifacts for certain collimator blocking ratios and
      blocking patterns, and the focus of this work is to study the relationship
      between the image quality and these two collimator factors. METHODS: A CBCT
      system with collimators was simulated following the typical geometry used in
      clinic. Different collimator designs were tested by varying the size and the
      number of the collimator slits, and at the same time, the ratio of transmitted
      beams to total beams was varied from 100% to 10%, resulting in hundreds of
      different simulation scenarios. Lung and pelvis phantoms created from patients CT
      images were used in the simulations, and an iterative reconstruction algorithm
      using the compressed sensing technique was adopted. The image quality was
      examined by root mean square errors (RMSEs) and compared with the conventional
      CBCT images. RESULTS: The CBCT image quality increases as the amount of beams
      passing through the collimators increases, and decreases as the size of the
      collimator slits increases. With ultra-high resolution collimators, the RMSEs
      were comparable to the conventional CBCT image quality until the beam
      transmission rate is reduced below 25%. CONCLUSIONS: Collimators can reduce the
      scatters and radiation dose, however, the collimated CBCT image quality is
      strongly dependent on both the collimator blocking ratio and the blocking
      pattern. To achieve image quality comparable to the conventional CBCT, the amount
      of information and data format must be adequate.

PMID- 24320525
TI  - Prospects for in vivo estimation of photon linear attenuation coefficients using
      postprocessing dual-energy CT imaging on a commercial scanner: comparison of
      analytic and polyenergetic statistical reconstruction algorithms.
AB  - PURPOSE: Accurate patient-specific photon cross-section information is needed to
      support more accurate model-based dose calculation for low energy photon-emitting
      modalities in medicine such as brachytherapy and kilovoltage x-ray imaging
      procedures. A postprocessing dual-energy CT (pDECT) technique for noninvasive in
      vivo estimation of photon linear attenuation coefficients has been experimentally
      implemented on a commercial CT scanner and its accuracy assessed in idealized
      phantom geometries. METHODS: Eight test materials of known composition and
      density were used to compare pDECT-estimated linear attenuation coefficients to
      NIST reference values over an energy range from 10 keV to 1 MeV. As statistical
      image reconstruction (SIR) has been shown to reconstruct images with less random
      and systematic error than conventional filtered backprojection (FBP), the pDECT
      technique was implemented with both an in-house polyenergetic SIR algorithm,
      alternating minimization (AM), as well as a conventional FBP reconstruction
      algorithm. Improvement from increased spectral separation was also investigated
      by filtering the high-energy beam with an additional 0.5 mm of tin. The law of
      propagated uncertainty was employed to assess the sensitivity of the pDECT
      process to errors in reconstructed images. RESULTS: Mean pDECT-estimated linear
      attenuation coefficients for the eight test materials agreed within 1% of NIST
      reference values for energies from 1 MeV down to 30 keV, with mean errors rising
      to between 3% and 6% at 10 keV, indicating that the method is unbiased when
      measurement and calibration phantom geometries are matched. Reconstruction with
      FBP and AM algorithms conferred similar mean pDECT accuracy. However, single
      voxel pDECT estimates reconstructed on a 1 * 1 * 3 mm(3) grid are shown to be
      highly sensitive to reconstructed image uncertainty; in some cases pDECT
      attenuation coefficient estimates exhibited standard deviations on the order of
      20% around the mean. Reconstruction with the statistical AM algorithm led to
      standard deviations roughly 40% to 60% less than FBP reconstruction. Additional
      tin filtration of the high energy beam exhibits similar pDECT estimation accuracy
      as the unfiltered beam, even when scanning with only 25% of the dose. Using the
      law of propagated uncertainty, low Z materials are found to be more sensitive to
      image reconstruction errors than high Z materials. Furthermore, it is estimated
      that reconstructed CT image uncertainty must be limited to less than 0.25% to
      achieve a target linear-attenuation coefficient estimation uncertainty of 3% at
      28 keV. CONCLUSIONS: That pDECT supports mean linear attenuation coefficient
      measurement accuracies of 1% of reference values for energies greater than 30 keV
      is encouraging. However, the sensitivity of the pDECT measurements to noise and
      systematic errors in reconstructed CT images warrants further investigation in
      more complex phantom geometries. The investigated statistical reconstruction
      algorithm, AM, reduced random measurement uncertainty relative to FBP owing to
      improved noise performance. These early results also support efforts to increase
      DE spectral separation, which can further reduce the pDECT sensitivity to
      measurement uncertainty.

PMID- 24320526
TI  - Comparative performance of modern digital mammography systems in a large breast
      screening program.
AB  - PURPOSE: To compare physical measures pertaining to image quality among digital
      mammography systems utilized in a large breast screening program. To examine
      qualitatively differences in these measures and differences in clinical cancer
      detection rates between CR and DR among sites within that program. METHODS: As
      part of the routine quality assurance program for screening, field measurements
      are made of several variables considered to correlate with the diagnostic quality
      of medical images including: modulation transfer function, noise equivalent
      quanta, d' (an index of lesion detectability) and air kerma to allow estimation
      of mean glandular dose. In addition, images of the mammography accreditation
      phantom are evaluated. RESULTS: It was found that overall there were marked
      differences between the performance measures of DR and CR mammography systems. In
      particular, the modulation transfer functions obtained with the DR systems were
      found to be higher, even for larger detector element sizes. Similarly, the noise
      equivalent quanta, d', and the phantom scores were higher, while the failure
      rates associated with low signal-to-noise ratio and high dose were lower with DR.
      These results were consistent with previous findings in the authors' program that
      the breast cancer detection rates at sites employing CR technology were, on
      average, 30.6% lower than those that used DR mammography. CONCLUSIONS: While the
      clinical study was not large enough to allow a statistically powered system-by
      system assessment of cancer detection accuracy, the physical measures expressing
      spatial resolution, and signal-to-noise ratio are consistent with the published
      finding that sites employing CR systems had lower cancer detection rates than
      those using DR systems for screening mammography.

PMID- 24320528
TI  - Quality assurance of asymmetric jaw alignment using 2D diode array.
AB  - PURPOSE: A method using a 2D diode array is proposed to measure the junction gap
      (or overlap) and dose with high precision for routine quality assurance of the
      asymmetric jaw alignment. METHODS: The central axis (CAX) of the radiation field
      was determined with a 15 * 15 cm(2) photon field at four cardinal collimator
      angles so that the junction gap (or overlap) can be measured with respect to the
      CAX. Two abutting fields having a field size of 15 cm (length along the axis
      parallel to the junction) * 7.5 cm (width along the axis perpendicular to the
      junction) were used to irradiate the 2D diode array (MapCHECK2) with 100 MU
      delivered at the photon energy of 6 MV. The collimator was slightly rotated at 15
      degrees  with respect to the beam central axis to increase the number of diodes
      effective on the measurement of junction gap. The junction gap and dose measured
      in high spatial resolution were compared to the conventional methods using an
      electronic portal imaging device (EPID) and radiochromic film, respectively. In
      addition, the reproducibility and sensitivity of the proposed method to the
      measurements of junction gap and dose were investigated. RESULTS: The junction
      gap (or overlap) and dose measured by MapCHECK2 agreed well to those measured by
      the conventional methods of EPID and film (the differences ranged from -0.01 to 0
      cm and from -1.34% to 0.6% for the gap and dose, respectively). No variation in
      the repeat measurements of the junction gap was found whereas the measurements of
      junction dose were found to vary in quite a small range over the days of
      measurement (0.21%-0.35%). While the sensitivity of the measured junction gap to
      the actual junction gap applied was the ideal value of 1 cm/cm as expected, the
      sensitivity of the junction dose to the actual junction gap increased as the
      junction gap (or overlap) decreased (maximum sensitivity: 201.7%/cm).
      CONCLUSIONS: The initial results suggest that the method is applicable for a
      comprehensive quality assurance of the asymmetric jaw alignment.

PMID- 24320527
TI  - High quality machine-robust image features: identification in nonsmall cell lung
      cancer computed tomography images.
AB  - PURPOSE: For nonsmall cell lung cancer (NSCLC) patients, quantitative image
      features extracted from computed tomography (CT) images can be used to improve
      tumor diagnosis, staging, and response assessment. For these findings to be
      clinically applied, image features need to have high intra and intermachine
      reproducibility. The objective of this study is to identify CT image features
      that are reproducible, nonredundant, and informative across multiple machines.
      METHODS: Noncontrast-enhanced, test-retest CT image pairs were obtained from 56
      NSCLC patients imaged on three CT machines from two institutions. Two machines
      ("M1" and "M2") used cine 4D-CT and one machine ("M3") used breath-hold helical
      3D-CT. Gross tumor volumes (GTVs) were semiautonomously segmented then pruned by
      removing voxels with CT numbers less than a prescribed Hounsfield unit (HU)
      cutoff. Three hundred and twenty eight quantitative image features were extracted
      from each pruned GTV based on its geometry, intensity histogram, absolute
      gradient image, co-occurrence matrix, and run-length matrix. For each machine,
      features with concordance correlation coefficient values greater than 0.90 were
      considered reproducible. The Dice similarity coefficient (DSC) and the Jaccard
      index (JI) were used to quantify reproducible feature set agreement between
      machines. Multimachine reproducible feature sets were created by taking the
      intersection of individual machine reproducible feature sets. Redundant features
      were removed through hierarchical clustering based on the average correlation
      between features across multiple machines. RESULTS: For all image types, GTV
      pruning was found to negatively affect reproducibility (reported results use no
      HU cutoff). The reproducible feature percentage was highest for average images
      (M1 = 90.5%, M2 = 94.5%, M1?M2 = 86.3%), intermediate for end-exhale images (M1 =
      75.0%, M2 = 71.0%, M1?M2 = 52.1%), and lowest for breath-hold images (M3 =
      61.0%). Between M1 and M2, the reproducible feature sets generated from end
      exhale images were relatively machine-sensitive (DSC = 0.71, JI = 0.55), and the
      reproducible feature sets generated from average images were relatively machine
      insensitive (DSC = 0.90, JI = 0.87). Histograms of feature pair correlation
      distances indicated that feature redundancy was machine-sensitive and image type
      sensitive. After hierarchical clustering, 38 features, 28 features, and 33
      features were found to be reproducible and nonredundant for M1?M2 (average
      images), M1?M2 (end-exhale images), and M3, respectively. When blinded to the
      presence of test-retest images, hierarchical clustering showed that the selected
      features were informative by correctly pairing 55 out of 56 test-retest images
      using only their reproducible, nonredundant feature set values. CONCLUSIONS:
      Image feature reproducibility and redundancy depended on both the CT machine and
      the CT image type. For each image type, the authors found a set of cross-machine
      reproducible, nonredundant, and informative image features that would be useful
      for future image-based models. Compared to end-exhale 4D-CT and breath-hold 3D
      CT, average 4D-CT derived image features showed superior multimachine
      reproducibility and are the best candidates for clinical correlation.

PMID- 24320529
TI  - Application of the optically stimulated luminescence (OSL) technique for mouse
      dosimetry in micro-CT imaging.
AB  - PURPOSE: Micro-CT is considered to be a powerful tool to investigate various
      models of disease on anesthetized animals. In longitudinal studies, the radiation
      dose delivered by the micro-CT to the same animal is a major concern as it could
      potentially induce spurious effects in experimental results. Optically stimulated
      luminescence dosimeters (OSLDs) are a relatively new kind of detector used in
      radiation dosimetry for medical applications. The aim of this work was to assess
      the dose delivered by the CT component of a micro-SPECT (single-photon emission
      computed tomography)/CT camera during a typical whole-body mouse study, using
      commercially available OSLDs based on Al2O3:C crystals. METHODS: CTDI (computed
      tomography dose index) was measured in micro-CT with a properly calibrated pencil
      ionization chamber using a rat-like phantom (60 mm in diameter) and a mouse-like
      phantom (30 mm in diameter). OSLDs were checked for reproducibility and linearity
      in the range of doses delivered by the micro-CT. Dose measurements obtained with
      OSLDs were compared to those of the ionization chamber to correct for the
      radiation quality dependence of OSLDs in the low-kV range. Doses to tissue were
      then investigated in phantoms and cadavers. A 30 mm diameter phantom,
      specifically designed to insert OSLDs, was used to assess radiation dose over a
      typical whole-body mouse imaging study. Eighteen healthy female BALB/c mice
      weighing 27.1 +/- 0.8 g (1 SD) were euthanized for small animal measurements.
      OLSDs were placed externally or implanted internally in nine different locations
      by an experienced animal technician. Five commonly used micro-CT protocols were
      investigated. RESULTS: CTDI measurements were between 78.0 +/- 2.1 and 110.7 +/-
      3.0 mGy for the rat-like phantom and between 169.3 +/- 4.6 and 203.6 +/- 5.5 mGy
      for the mouse-like phantom. On average, the displayed CTDI at the operator
      console was underestimated by 1.19 for the rat-like phantom and 2.36 for the
      mouse-like phantom. OSLDs exhibited a reproducibility of 2.4% and good linearity
      was found between 60 and 450 mGy. The energy scaling factor was calculated to be
      between 1.80 +/- 0.16 and 1.86 +/- 0.16, depending on protocol used. In phantoms,
      mean doses to tissue over a whole-body CT examination were ranging from 186.4 +/-
      7.6 to 234.9 +/- 7.1 mGy. In mice, mean doses to tissue in the mouse trunk
      (thorax, abdomen, pelvis, and flanks) were between 213.0 +/- 17.0 and 251.2 +/-
      13.4 mGy. Skin doses (3 OSLDs) were much higher with average doses between 350.6
      +/- 25.3 and 432.5 +/- 34.1 mGy. The dose delivered during a topogram was found
      to be below 10 mGy. Use of the multimouse bed of the system gave a significantly
      20%-40% lower dose per animal (p < 0.05). CONCLUSIONS: Absorbed doses in micro-CT
      were found to be relatively high. In micro-SPECT/CT imaging, the micro-CT unit is
      mainly used to produce a localization frame. As a result, users should pay
      attention to adjustable CT parameters so as to minimize the radiation dose and
      avoid any adverse radiation effects which may interfere with biological
      parameters studied.

PMID- 24320530
TI  - Dependence with air density of the response of the PTW SourceCheck ionization
      chamber for low energy brachytherapy sources.
AB  - PURPOSE: Air-communicating well ionization chambers are commonly used to assess
      air kerma strength of sources used in brachytherapy. The signal produced is
      supposed to be proportional to the air density within the chamber and, therefore,
      a density-independent air kerma strength is obtained when the measurement is
      corrected to standard atmospheric conditions using the usual temperature and
      pressure correction factor. Nevertheless, when assessing low energy sources, the
      ionization chambers may not fulfill that condition and a residual density
      dependence still remains after correction. In this work, the authors examined the
      behavior of the PTW 34051 SourceCheck ionization chamber when measuring the air
      kerma strength of (125)I seeds. METHODS: Four different SourceCheck chambers were
      analyzed. With each one of them, two series of measurements of the air kerma
      strength for (125)I selectSeed(TM) brachytherapy sources were performed inside a
      pressure chamber and varying the pressure in a range from 747 to 1040 hPa (560 to
      780 mm Hg). The temperature and relative humidity were kept basically constant.
      An analogous experiment was performed by taking measurements at different
      altitudes above sea level. RESULTS: Contrary to other well-known ionization
      chambers, like the HDR1000 PLUS, in which the temperature-pressure correction
      factor overcorrects the measurements, in the SourceCheck ionization chamber they
      are undercorrected. At a typical atmospheric situation of 933 hPa (700 mm Hg) and
      20  degrees C, this undercorrection turns out to be 1.5%. Corrected measurements
      show a residual linear dependence on the density and, as a consequence, an
      additional density dependent correction must be applied. The slope of this
      residual linear density dependence is different for each SourceCheck chamber
      investigated. The results obtained by taking measurements at different altitudes
      are compatible with those obtained with the pressure chamber. CONCLUSIONS:
      Variations of the altitude and changes in the weather conditions may produce
      significant density corrections, and that effect should be taken into account.
      This effect is chamber-dependent, indicating that a specific calibration is
      necessary for each particular chamber. To our knowledge, this correction has not
      been considered so far for SourceCheck ionization chambers, but its magnitude
      cannot be neglected in clinical practice. The atmospheric pressure and
      temperature at which the chamber was calibrated need to be taken into account,
      and they should be reported in the calibration certificate. In addition, each
      institution should analyze the particular response of its SourceCheck ionization
      chamber and compute the adequate correction factors. In the absence of a suitable
      pressure chamber, a possibility for this assessment is to take measurements at
      different altitudes, spanning a wide enough air density range.

PMID- 24320531
TI  - Verification of Gamma Knife extend system based fractionated treatment planning
      using EBT2 film.
AB  - PURPOSE: This paper presents EBT2 film verification of fractionated treatment
      planning with the Gamma Knife (GK) extend system, a relocatable frame system for
      multiple-fraction or serial multiple-session radiosurgery. METHODS: A human head
      shaped phantom simulated the verification process for fractionated Gamma Knife
      treatment. Phantom preparation for Extend Frame based treatment planning involved
      creating a dental impression, fitting the phantom to the frame system, and
      acquiring a stereotactic computed tomography (CT) scan. A CT scan (Siemens,
      Emotion 6) of the phantom was obtained with following parameters: Tube voltage-
      110 kV, tube current--280 mA, pixel size--0.5 * 0.5 and 1 mm slice thickness. A
      treatment plan with two 8 mm collimator shots and three sectors blocking in each
      shot was made. Dose prescription of 4 Gy at 100% was delivered for the first
      fraction out of the two fractions planned. Gafchromic EBT2 film (ISP Wayne, NJ)
      was used as 2D verification dosimeter in this process. Films were cut and placed
      inside the film insert of the phantom for treatment dose delivery. Meanwhile a
      set of films from the same batch were exposed from 0 to 12 Gy doses for
      calibration purposes. An EPSON (Expression 10000 XL) scanner was used for
      scanning the exposed films in transparency mode. Scanned films were analyzed with
      inhouse written MATLAB codes. RESULTS: Gamma index analysis of film measurement
      in comparison with TPS calculated dose resulted in high pass rates >90% for
      tolerance criteria of 1%/1 mm. The isodose overlay and linear dose profiles of
      film measured and computed dose distribution on sagittal and coronal plane were
      in close agreement. CONCLUSIONS: Through this study, the authors propose
      treatment verification QA method for Extend frame based fractionated Gamma Knife
      radiosurgery using EBT2 film.

PMID- 24320532
TI  - Template-based automatic breast segmentation on MRI by excluding the chest
      region.
AB  - PURPOSE: Methods for quantification of breast density on MRI using semiautomatic
      approaches are commonly used. In this study, the authors report on a fully
      automatic chest template-based method. METHODS: Nonfat-suppressed breast MR
      images from 31 healthy women were analyzed. Among them, one case was randomly
      selected and used as the template, and the remaining 30 cases were used for
      testing. Unlike most model-based breast segmentation methods that use the breast
      region as the template, the chest body region on a middle slice was used as the
      template. Within the chest template, three body landmarks (thoracic spine and
      bilateral boundary of the pectoral muscle) were identified for performing the
      initial V-shape cut to determine the posterior lateral boundary of the breast.
      The chest template was mapped to each subject's image space to obtain a subject
      specific chest model for exclusion. On the remaining image, the chest wall muscle
      was identified and excluded to obtain clean breast segmentation. The chest and
      muscle boundaries determined on the middle slice were used as the reference for
      the segmentation of adjacent slices, and the process continued superiorly and
      inferiorly until all 3D slices were segmented. The segmentation results were
      evaluated by an experienced radiologist to mark voxels that were wrongly included
      or excluded for error analysis. RESULTS: The breast volumes measured by the
      proposed algorithm were very close to the radiologist's corrected volumes,
      showing a % difference ranging from 0.01% to 3.04% in 30 tested subjects with a
      mean of 0.86% +/- 0.72%. The total error was calculated by adding the inclusion
      and the exclusion errors (so they did not cancel each other out), which ranged
      from 0.05% to 6.75% with a mean of 3.05% +/- 1.93%. The fibroglandular tissue
      segmented within the breast region determined by the algorithm and the
      radiologist were also very close, showing a % difference ranging from 0.02% to
      2.52% with a mean of 1.03% +/- 1.03%. The total error by adding the inclusion and
      exclusion errors ranged from 0.16% to 11.8%, with a mean of 2.89% +/- 2.55%.
      CONCLUSIONS: The automatic chest template-based breast MRI segmentation method
      worked well for cases with different body and breast shapes and different density
      patterns. Compared to the radiologist-established truth, the mean difference in
      segmented breast volume was approximately 1%, and the total error by considering
      the additive inclusion and exclusion errors was approximately 3%. This method may
      provide a reliable tool for MRI-based segmentation of breast density.

PMID- 24320533
TI  - Automated fibroglandular tissue segmentation and volumetric density estimation in
      breast MRI using an atlas-aided fuzzy C-means method.
AB  - PURPOSE: Breast magnetic resonance imaging (MRI) plays an important role in the
      clinical management of breast cancer. Studies suggest that the relative amount of
      fibroglandular (i.e., dense) tissue in the breast as quantified in MR images can
      be predictive of the risk for developing breast cancer, especially for high-risk
      women. Automated segmentation of the fibroglandular tissue and volumetric density
      estimation in breast MRI could therefore be useful for breast cancer risk
      assessment. METHODS: In this work the authors develop and validate a fully
      automated segmentation algorithm, namely, an atlas-aided fuzzy C-means (FCM
      Atlas) method, to estimate the volumetric amount of fibroglandular tissue in
      breast MRI. The FCM-Atlas is a 2D segmentation method working on a slice-by-slice
      basis. FCM clustering is first applied to the intensity space of each 2D MR slice
      to produce an initial voxelwise likelihood map of fibroglandular tissue. Then a
      prior learned fibroglandular tissue likelihood atlas is incorporated to refine
      the initial FCM likelihood map to achieve enhanced segmentation, from which the
      absolute volume of the fibroglandular tissue (|FGT|) and the relative amount
      (i.e., percentage) of the |FGT| relative to the whole breast volume (FGT%) are
      computed. The authors' method is evaluated by a representative dataset of 60 3D
      bilateral breast MRI scans (120 breasts) that span the full breast density range
      of the American College of Radiology Breast Imaging Reporting and Data System.
      The automated segmentation is compared to manual segmentation obtained by two
      experienced breast imaging radiologists. Segmentation performance is assessed by
      linear regression, Pearson's correlation coefficients, Student's paired t-test,
      and Dice's similarity coefficients (DSC). RESULTS: The inter-reader correlation
      is 0.97 for FGT% and 0.95 for |FGT|. When compared to the average of the two
      readers' manual segmentation, the proposed FCM-Atlas method achieves a
      correlation of r = 0.92 for FGT% and r = 0.93 for |FGT|, and the automated
      segmentation is not statistically significantly different (p = 0.46 for FGT% and
      p = 0.55 for |FGT|). The bilateral correlation between left breasts and right
      breasts for the FGT% is 0.94, 0.92, and 0.95 for reader 1, reader 2, and the FCM
      Atlas, respectively; likewise, for the |FGT|, it is 0.92, 0.92, and 0.93,
      respectively. For the spatial segmentation agreement, the automated algorithm
      achieves a DSC of 0.69 +/- 0.1 when compared to reader 1 and 0.61 +/- 0.1 for
      reader 2, respectively, while the DSC between the two readers' manual
      segmentation is 0.67 +/- 0.15. Additional robustness analysis shows that the
      segmentation performance of the authors' method is stable both with respect to
      selecting different cases and to varying the number of cases needed to construct
      the prior probability atlas. The authors' results also show that the proposed FCM
      Atlas method outperforms the commonly used two-cluster FCM-alone method. The
      authors' method runs at ~5 min for each 3D bilateral MR scan (56 slices) for
      computing the FGT% and |FGT|, compared to ~55 min needed for manual segmentation
      for the same purpose. CONCLUSIONS: The authors' method achieves robust
      segmentation and can serve as an efficient tool for processing large clinical
      datasets for quantifying the fibroglandular tissue content in breast MRI. It
      holds a great potential to support clinical applications in the future including
      breast cancer risk assessment.

PMID- 24320534
TI  - An RF dosimeter for independent SAR measurement in MRI scanners.
AB  - PURPOSE: The monitoring and management of radio frequency (RF) exposure is
      critical for ensuring magnetic resonance imaging (MRI) safety. Commercial MRI
      scanners can overestimate specific absorption rates (SAR) and improperly restrict
      clinical MRI scans or the application of new MRI sequences, while underestimation
      of SAR can lead to tissue heating and thermal injury. Accurate scanner
      independent RF dosimetry is essential for measuring actual exposure when SAR is
      critical for ensuring regulatory compliance and MRI safety, for establishing RF
      exposure while evaluating interventional leads and devices, and for routine MRI
      quality assessment by medical physicists. However, at present there are no
      scanner-independent SAR dosimeters. METHODS: An SAR dosimeter with an RF
      transducer comprises two orthogonal, rectangular copper loops and a spherical MRI
      phantom. The transducer is placed in the magnet bore and calibrated to
      approximate the resistive loading of the scanner's whole-body birdcage RF coil
      for human subjects in Philips, GE and Siemens 3 tesla (3T) MRI scanners. The
      transducer loop reactances are adjusted to minimize interference with the
      transmit RF field (B1) at the MRI frequency. Power from the RF transducer is
      sampled with a high dynamic range power monitor and recorded on a computer. The
      deposited power is calibrated and tested on eight different MRI scanners. Whole
      body absorbed power vs weight and body mass index (BMI) is measured directly on
      26 subjects. RESULTS: A single linear calibration curve sufficed for RF dosimetry
      at 127.8 MHz on three different Philips and three GE 3T MRI scanners. An RF
      dosimeter operating at 123.2 MHz on two Siemens 3T scanners required a separate
      transducer and a slightly different calibration curve. Measurement accuracy was
      ~3%. With the torso landmarked at the xiphoid, human adult whole-body absorbed
      power varied approximately linearly with patient weight and BMI. This indicates
      that whole-body torso SAR is on average independent of the imaging subject,
      albeit with fluctuations. CONCLUSIONS: Our 3T RF dosimeter and transducers
      accurately measure RF exposure in body-equivalent loads and provide scanner
      independent assessments of whole-body RF power deposition for establishing safety
      compliance useful for MRI sequence and device testing.

PMID- 24320535
TI  - High spatial resolution brain functional MRI using submillimeter balanced steady
      state free precession acquisition.
AB  - PURPOSE: One of the technical advantages of functional magnetic resonance imaging
      (fMRI) is its precise localization of changes from neuronal activities. While
      current practice of fMRI acquisition at voxel size around 3 * 3 * 3 mm(3)
      achieves satisfactory results in studies of basic brain functions, higher spatial
      resolution is required in order to resolve finer cortical structures. This study
      investigated spatial resolution effects on brain fMRI experiments using balanced
      steady-state free precession (bSSFP) imaging with 0.37 mm(3) voxel volume at 3.0
      T. METHODS: In fMRI experiments, full and unilateral visual field 5 Hz flashing
      checkerboard stimulations were given to healthy subjects. The bSSFP imaging
      experiments were performed at three different frequency offsets to widen the
      coverage, with functional activations in the primary visual cortex analyzed using
      the general linear model. Variations of the spatial resolution were achieved by
      removing outer k-space data components. RESULTS: Results show that a reduction in
      voxel volume from 3.44 * 3.44 * 2 mm(3) to 0.43 * 0.43 * 2 mm(3) has resulted in
      an increase of the functional activation signals from (7.7 +/- 1.7)% to (20.9 +/-
      2.0)% at 3.0 T, despite of the threefold SNR decreases in the original images,
      leading to nearly invariant functional contrast-to-noise ratios (fCNR) even at
      high spatial resolution. Activation signals aligning nicely with gray matter
      sulci at high spatial resolution would, on the other hand, have possibly been
      mistaken as noise at low spatial resolution. CONCLUSIONS: It is concluded that
      the bSSFP sequence is a plausible technique for fMRI investigations at
      submillimeter voxel widths without compromising fCNR. The reduction of partial
      volume averaging with nonactivated brain tissues to retain fCNR is uniquely
      suitable for high spatial resolution applications such as the resolving of
      columnar organization in the brain.

PMID- 24320536
TI  - Breast density quantification using magnetic resonance imaging (MRI) with bias
      field correction: a postmortem study.
AB  - PURPOSE: Quantification of breast density based on three-dimensional breast MRI
      may provide useful information for the early detection of breast cancer. However,
      the field inhomogeneity can severely challenge the computerized image
      segmentation process. In this work, the effect of the bias field in breast
      density quantification has been investigated with a postmortem study. METHODS: T1
      weighted images of 20 pairs of postmortem breasts were acquired on a 1.5 T breast
      MRI scanner. Two computer-assisted algorithms were used to quantify the
      volumetric breast density. First, standard fuzzy c-means (FCM) clustering was
      used on raw images with the bias field present. Then, the coherent local
      intensity clustering (CLIC) method estimated and corrected the bias field during
      the iterative tissue segmentation process. Finally, FCM clustering was performed
      on the bias-field-corrected images produced by CLIC method. The left-right
      correlation for breasts in the same pair was studied for both segmentation
      algorithms to evaluate the precision of the tissue classification. Finally, the
      breast densities measured with the three methods were compared to the gold
      standard tissue compositions obtained from chemical analysis. The linear
      correlation coefficient, Pearson's r, was used to evaluate the two image
      segmentation algorithms and the effect of bias field. RESULTS: The CLIC method
      successfully corrected the intensity inhomogeneity induced by the bias field. In
      left-right comparisons, the CLIC method significantly improved the slope and the
      correlation coefficient of the linear fitting for the glandular volume
      estimation. The left-right breast density correlation was also increased from
      0.93 to 0.98. When compared with the percent fibroglandular volume (%FGV) from
      chemical analysis, results after bias field correction from both the CLIC the FCM
      algorithms showed improved linear correlation. As a result, the Pearson's r
      increased from 0.86 to 0.92 with the bias field correction. CONCLUSIONS: The
      investigated CLIC method significantly increased the precision and accuracy of
      breast density quantification using breast MRI images by effectively correcting
      the bias field. It is expected that a fully automated computerized algorithm for
      breast density quantification may have great potential in clinical MRI
      applications.

PMID- 24320537
TI  - A line-source method for aligning on-board and other pinhole SPECT systems.
AB  - PURPOSE: In order to achieve functional and molecular imaging as patients are in
      position for radiation therapy, a robotic multipinhole SPECT system is being
      developed. Alignment of the SPECT system-to the linear accelerator (LINAC)
      coordinate frame and to the coordinate frames of other on-board imaging systems
      such as cone-beam CT (CBCT)-is essential for target localization and image
      reconstruction. An alignment method that utilizes line sources and one pinhole
      projection is proposed and investigated to achieve this goal. Potentially, this
      method could also be applied to the calibration of the other pinhole SPECT
      systems. METHODS: An alignment model consisting of multiple alignment parameters
      was developed which maps line sources in three-dimensional (3D) space to their
      two-dimensional (2D) projections on the SPECT detector. In a computer-simulation
      study, 3D coordinates of line-sources were defined in a reference room coordinate
      frame, such as the LINAC coordinate frame. Corresponding 2D line-source
      projections were generated by computer simulation that included SPECT blurring
      and noise effects. The Radon transform was utilized to detect angles (alpha) and
      offsets (rho) of the line-source projections. Alignment parameters were then
      estimated by a nonlinear least squares method, based on the alpha and rho values
      and the alignment model. Alignment performance was evaluated as a function of
      number of line sources, Radon transform accuracy, finite line-source width,
      intrinsic camera resolution, Poisson noise, and acquisition geometry.
      Experimental evaluations were performed using a physical line-source phantom and
      a pinhole-collimated gamma camera attached to a robot. RESULTS: In computer
      simulation studies, when there was no error in determining angles (alpha) and
      offsets (rho) of the measured projections, six alignment parameters (three
      translational and three rotational) were estimated perfectly using three line
      sources. When angles (alpha) and offsets (rho) were provided by the Radon
      transform, estimation accuracy was reduced. The estimation error was associated
      with rounding errors of Radon transform, finite line-source width, Poisson noise,
      number of line sources, intrinsic camera resolution, and detector acquisition
      geometry. Statistically, the estimation accuracy was significantly improved by
      using four line sources rather than three and by thinner line-source projections
      (obtained by better intrinsic detector resolution). With five line sources,
      median errors were 0.2 mm for the detector translations, 0.7 mm for the detector
      radius of rotation, and less than 0.5 degrees  for detector rotation, tilt, and
      twist. In experimental evaluations, average errors relative to a different,
      independent registration technique were about 1.8 mm for detector translations,
      1.1 mm for the detector radius of rotation (ROR), 0.5 degrees  and 0.4 degrees 
      for detector rotation and tilt, respectively, and 1.2 degrees  for detector
      twist. CONCLUSIONS: Alignment parameters can be estimated using one pinhole
      projection of line sources. Alignment errors are largely associated with limited
      accuracy of the Radon transform in determining angles (alpha) and offsets (rho)
      of the line-source projections. This alignment method may be important for
      multipinhole SPECT, where relative pinhole alignment may vary during rotation.
      For pinhole and multipinhole SPECT imaging on-board radiation therapy machines,
      the method could provide alignment of SPECT coordinates with those of CBCT and
      the LINAC.

PMID- 24320539
TI  - Evaluation of a semiautomated lung mass calculation technique for internal
      dosimetry applications.
AB  - PURPOSE: The authors sought to evaluate a simple, semiautomated lung mass
      estimation method using computed tomography (CT) scans obtained using a variety
      of acquisition techniques and reconstruction parameters for mass correction of
      medical internal radiation dose-based internal radionuclide radiation absorbed
      dose estimates. METHODS: CT scans of 27 patients with lung cancer undergoing
      stereotactic body radiation therapy treatment planning with PET/CT were analyzed
      retrospectively. For each patient, free-breathing (FB) and respiratory-gated 4DCT
      scans were acquired. The 4DCT scans were sorted into ten respiratory phases,
      representing one complete respiratory cycle. An average CT reconstruction was
      derived from the ten-phase reconstructions. Mid expiration breath-hold CT scans
      were acquired in the same session for many patients. Deep inspiration breath-hold
      diagnostic CT scans of many of the patients were obtained from different scanning
      sessions at similar time points to evaluate the effect of contrast administration
      and maximum inspiration breath-hold. Lung mass estimates were obtained using all
      CT scan types, and intercomparisons made to assess lung mass variation according
      to scan type. Lung mass estimates using the FB CT scans from PET/CT examinations
      of another group of ten male and ten female patients who were 21-30 years old and
      did not have lung disease were calculated and compared with reference lung mass
      values. To evaluate the effect of varying CT acquisition and reconstruction
      parameters on lung mass estimation, an anthropomorphic chest phantom was scanned
      and reconstructed with different CT parameters. CT images of the lungs were
      segmented using the OsiriX MD software program with a seed point of about -850 HU
      and an interval of 1000. Lung volume, and mean lung, tissue, and air HUs were
      recorded for each scan. Lung mass was calculated by assuming each voxel was a
      linear combination of only air and tissue. The specific gravity of lung volume
      was calculated using the formula (lung HU - air HU)/(tissue HU - air HU), and
      mass = specific gravity * total volume * 1.04 g/cm(3). RESULTS: The range of
      calculated lung masses was 0.51-1.29 kg. The average male and female lung masses
      during FB CT were 0.80 and 0.71 kg, respectively. The calculated lung mass varied
      across the respiratory cycle but changed to a lesser degree than did lung volume
      measurements (7.3% versus 15.4%). Lung masses calculated using deep inspiration
      breath-hold and average CT were significantly larger (p < 0.05) than were some
      masses calculated using respiratory-phase and FB CT. Increased voxel size and
      smooth reconstruction kernels led to high lung mass estimates owing to partial
      volume effects. CONCLUSIONS: Organ mass correction is an important component of
      patient-specific internal radionuclide dosimetry. Lung mass calculation
      necessitates scan-based density correction to account for volume changes owing to
      respiration. The range of lung masses in the authors' patient population
      represents lung doses for the same absorbed energy differing from 25% below to
      64% above the dose found using reference phantom organ masses. With proper
      management of acquisition parameters and selection of FB or midexpiration breath
      hold scans, lung mass estimates with about 10% population precision may be
      achieved.

PMID- 24320538
TI  - A method to synchronize signals from multiple patient monitoring devices through
      a single input channel for inclusion in list-mode acquisitions.
AB  - PURPOSE: This technical note documents a method that the authors developed for
      combining a signal to synchronize a patient-monitoring device with a second
      physiological signal for inclusion into list-mode acquisition. Our specific
      application requires synchronizing an external patient motion-tracking system
      with a medical imaging system by multiplexing the tracking input with the ECG
      input. The authors believe that their methodology can be adapted for use in a
      variety of medical imaging modalities including single photon emission computed
      tomography (SPECT) and positron emission tomography (PET). METHODS: The authors
      insert a unique pulse sequence into a single physiological input channel. This
      sequence is then recorded in the list-mode acquisition along with the R-wave
      pulse used for ECG gating. The specific form of our pulse sequence allows for
      recognition of the time point being synchronized even when portions of the pulse
      sequence are lost due to collisions with R-wave pulses. This was achieved by
      altering our software used in binning the list-mode data to recognize even a
      portion of our pulse sequence. Limitations on heart rates at which our pulse
      sequence could be reliably detected were investigated by simulating the mixing of
      the two signals as a function of heart rate and time point during the cardiac
      cycle at which our pulse sequence is mixed with the cardiac signal. RESULTS: The
      authors have successfully achieved accurate temporal synchronization of our
      motion-tracking system with acquisition of SPECT projections used in 17 recent
      clinical research cases. In our simulation analysis the authors determined that
      synchronization to enable compensation for body and respiratory motion could be
      achieved for heart rates up to 125 beats-per-minute (bpm). CONCLUSIONS:
      Synchronization of list-mode acquisition with external patient monitoring devices
      such as those employed in motion-tracking can reliably be achieved using a simple
      method that can be implemented using minimal external hardware and software
      modification through a single input channel, while still recording cardiac gating
      signals.

PMID- 24320541
TI  - A quantification strategy for missing bone mass in case of osteolytic bone
      lesions.
AB  - PURPOSE: Most of the patients who died of breast cancer have developed bone
      metastases. To understand the pathogenesis of bone metastases and to analyze
      treatment response of different bone remodeling therapies, preclinical animal
      models are examined. In breast cancer, bone metastases are often bone
      destructive. To assess treatment response of bone remodeling therapies, the
      volumes of these lesions have to be determined during the therapy process. The
      manual delineation of missing structures, especially if large parts are missing,
      is very time-consuming and not reproducible. Reproducibility is highly important
      to have comparable results during the therapy process. Therefore, a computerized
      approach is needed. Also for the preclinical research, a reproducible measurement
      of the lesions is essential. Here, the authors present an automated segmentation
      method for the measurement of missing bone mass in a preclinical rat model with
      bone metastases in the hind leg bones based on 3D CT scans. METHODS: The affected
      bone structure is compared to a healthy model. Since in this preclinical rat
      trial the metastasis only occurs on the right hind legs, which is assured by
      using vessel clips, the authors use the left body side as a healthy model. The
      left femur is segmented with a statistical shape model which is initialised using
      the automatically segmented medullary cavity. The left tibia and fibula are
      segmented using volume growing starting at the tibia medullary cavity and
      stopping at the femur boundary. Masked images of both segmentations are mirrored
      along the median plane and transferred manually to the position of the affected
      bone by rigid registration. Affected bone and healthy model are compared based on
      their gray values. If the gray value of a voxel indicates bone mass in the
      healthy model and no bone in the affected bone, this voxel is considered to be
      osteolytic. RESULTS: The lesion segmentations complete the missing bone
      structures in a reasonable way. The mean ratio vr/vm of the reconstructed bone
      volume vr and the healthy model bone volume vm is 1.07, which indicates a good
      reconstruction of the modified bone. CONCLUSIONS: The qualitative and
      quantitative comparison of manual and semi-automated segmentation results have
      shown that comparing a modified bone structure with a healthy model can be used
      to identify and measure missing bone mass in a reproducible way.

PMID- 24320540
TI  - The application of sparse arrays in high frequency transcranial focused
      ultrasound therapy: a simulation study.
AB  - PURPOSE: Transcranial focused ultrasound is an emerging therapeutic modality that
      can be used to perform noninvasive neurosurgical procedures. The current clinical
      transcranial phased array operates at 650 kHz, however the development of a
      higher frequency array would enable more precision, while reducing the risk of
      standing waves. However, the smaller wavelength and the skull's increased
      distortion at this frequency are problematic. It would require an order of
      magnitude more elements to create such an array. Random sparse arrays enable
      steering of a therapeutic array with fewer elements. However, the tradeoffs
      inherent in the use of sparsity in a transcranial phased array have not been
      systematically investigated and so the objective of this simulation study is to
      investigate the effect of sparsity on transcranial arrays at a frequency of 1.5
      MHz that provides small focal spots for precise exposure control. METHODS:
      Transcranial sonication simulations were conducted using a multilayer Rayleigh
      Sommerfeld propagation model. Element size and element population were varied and
      the phased array's ability to steer was assessed. RESULTS: The focal pressures
      decreased proportionally as elements were removed. However, off-focus hotspots
      were generated if a high degree of steering was attempted with very sparse
      arrays. A phased array consisting of 1588 elements 3 mm in size, a 10%
      population, was appropriate for steering up to 4 cm in all directions. However, a
      higher element population would be required if near-skull sonication is desired.
      CONCLUSIONS: This study demonstrated that the development of a sparse,
      hemispherical array at 1.5 MHz could enable more precision in therapies that
      utilize lower intensity sonications.

PMID- 24320542
TI  - An elastography method based on the scanning contact resonance of a piezoelectric
      cantilever.
AB  - PURPOSE: Most tissues may become significantly stiffer than their normal states
      when there are lesions inside. The tissue's modulus can then act as an
      identification parameter for clinic diagnosis of tumors or fibrosis, which leads
      to elastography. This study introduces a novel elastography method that can be
      used for modulus imaging of superficial organs. METHODS: This method is based on
      the scanning contact-resonance of a unimorph piezoelectric cantilever. The
      cantilever vibrates in its bending mode with the tip pressed tightly on the
      sample. The contact resonance frequency of the cantilever-sample system is
      tracked at each scanning point, from which the sample's modulus can be derived
      based on a beam dynamic model and a contact mechanics model. Scanning is
      performed by a three-dimensional motorized stage and the whole system is
      controlled by a homemade software program based on LabVIEW. RESULTS: Testing on
      in vitro beef tissues indicates that the fat and the muscle can be easily
      distinguished using this system, and the accuracy of the modulus measurement can
      be comparable with that of nanoindentation. Imaging on homemade gelatin phantoms
      shows that the depth information of the abnormalities can be qualitatively
      obtained by varying the pressing force. The detection limit of this elastography
      method is specially examined both experimentally and numerically. Results show
      that it can detect the typical lesions in superficial organs with the depth of
      several centimeters. The lateral resolution of this elastography method/system is
      better than 0.5 mm, and could be further enhanced by using more scanning points.
      CONCLUSIONS: The proposed elastography system can be regarded as a sensitive
      palpation robot, which may be very promising in early diagnosis of tumors in
      superficial organs such as breast and thyroid.

PMID- 24320543
TI  - Inter-slice bidirectional registration-based segmentation of the prostate gland
      in MR and CT image sequences.
AB  - PURPOSE: Accurate segmentation and volume estimation of the prostate gland in
      magnetic resonance (MR) and computed tomography (CT) images are necessary steps
      in diagnosis, treatment, and monitoring of prostate cancer. This paper presents
      an algorithm for the prostate gland volume estimation based on the semiautomated
      segmentation of individual slices in T2-weighted MR and CT image sequences.
      METHODS: The proposed Inter-Slice Bidirectional Registration-based Segmentation
      (iBRS) algorithm relies on interslice image registration of volume data to
      segment the prostate gland without the use of an anatomical atlas. It requires
      the user to mark only three slices in a given volume dataset, i.e., the first,
      middle, and last slices. Next, the proposed algorithm uses a registration
      algorithm to autosegment the remaining slices. We conducted comprehensive
      experiments to measure the performance of the proposed algorithm using three
      registration methods (i.e., rigid, affine, and nonrigid techniques). RESULTS: The
      results with the proposed technique were compared with manual marking using
      prostate MR and CT images from 117 patients. Manual marking was performed by an
      expert user for all 117 patients. The median accuracies for individual slices
      measured using the Dice similarity coefficient (DSC) were 92% and 91% for MR and
      CT images, respectively. The iBRS algorithm was also evaluated regarding user
      variability, which confirmed that the algorithm was robust to interuser
      variability when marking the prostate gland. CONCLUSIONS: The proposed algorithm
      exploits the interslice data redundancy of the images in a volume dataset of MR
      and CT images and eliminates the need for an atlas, minimizing the computational
      cost while producing highly accurate results which are robust to interuser
      variability.

PMID- 24320544
TI  - Respiratory effort correction strategies to improve the reproducibility of lung
      expansion measurements.
AB  - PURPOSE: Four-dimensional computed tomography (4DCT) can be used to make
      measurements of pulmonary function longitudinally. The sensitivity of such
      measurements to identify change depends on measurement uncertainty. Previously,
      intrasubject reproducibility of Jacobian-based measures of lung tissue expansion
      was studied in two repeat prior-RT 4DCT human acquisitions. Difference in
      respiratory effort such as breathing amplitude and frequency may affect
      longitudinal function assessment. In this study, the authors present
      normalization schemes that correct ventilation images for variations in
      respiratory effort and assess the reproducibility improvement after effort
      correction. METHODS: Repeat 4DCT image data acquired within a short time interval
      from 24 patients prior to radiation therapy (RT) were used for this analysis.
      Using a tissue volume preserving deformable image registration algorithm,
      Jacobian ventilation maps in two scanning sessions were computed and compared on
      the same coordinate for reproducibility analysis. In addition to computing the
      ventilation maps from end expiration to end inspiration, the authors investigated
      the effort normalization strategies using other intermediated inspiration phases
      upon the principles of equivalent tidal volume (ETV) and equivalent lung volume
      (ELV). Scatter plots and mean square error of the repeat ventilation maps and the
      Jacobian ratio map were generated for four conditions: no effort correction,
      global normalization, ETV, and ELV. In addition, gamma pass rate was calculated
      from a modified gamma index evaluation between two ventilation maps, using
      acceptance criterions of 2 mm distance-to-agreement and 5% ventilation
      difference. RESULTS: The pattern of regional pulmonary ventilation changes as
      lung volume changes. All effort correction strategies improved reproducibility
      when changes in respiratory effort were greater than 150 cc (p < 0.005 with
      regard to the gamma pass rate). Improvement of reproducibility was correlated
      with respiratory effort difference (R = 0.744 for ELV in the cohort with tidal
      volume difference greater than 100 cc). In general for all subjects, global
      normalization, ETV and ELV significantly improved reproducibility compared to no
      effort correction (p = 0.009, 0.002, 0.005 respectively). When tidal volume
      difference was small (less than 100 cc), none of the three effort correction
      strategies improved reproducibility significantly (p = 0.52, 0.46, 0.46
      respectively). For the cohort (N = 13) with tidal volume difference greater than
      100 cc, the average gamma pass rate improves from 57.3% before correction to
      66.3% after global normalization, and 76.3% after ELV. ELV was found to be
      significantly better than global normalization (p = 0.04 for all subjects, and p
      = 0.003 for the cohort with tidal volume difference greater than 100 cc).
      CONCLUSIONS: All effort correction strategies improve the reproducibility of the
      authors' pulmonary ventilation measures, and the improvement of reproducibility
      is highly correlated with the changes in respiratory effort. ELV gives better
      results as effort difference increase, followed by ETV, then global. However,
      based on the spatial and temporal heterogeneity in the lung expansion rate, a
      single scaling factor (e.g., global normalization) appears to be less accurate to
      correct the ventilation map when changes in respiratory effort are large.

PMID- 24320547
TI  - A new site of milia en plaque: report of a case and review of the literature.

PMID- 24320548
TI  - Reaction of NO(2) with selected conjugated alkenes.
AB  - The gas phase reactions of selected alkenes (isoprene, myrcene, ocimene, and 1,3
      cyclohexadiene) with NO2 under dark condition have been investigated at T ~ 298 K
      and P ~ 760 Torr of purified air. The kinetic studies were performed under pseudo
      first-order conditions using a large excess of NO2 concentration to those of the
      alkenes. The rate coefficients (in 10(-19) cm(3) molecule(-1) s(-1)) obtained are
      1.1 +/- 0.2 for isoprene, 2.5 +/- 0.3 for myrcene, 8.5 +/- 1.2 for ocimene, and
      15 +/- 1 for 1,3-cyclohexadiene. Several products were identified by using in
      situ Fourier transform infrared (FT-IR) spectrometry, and acetone was found to be
      the major product from the reactions of NO2 with myrcene and ocimene, with a
      formation yield of 22 +/- 3% and 26 +/- 7%, respectively. The oxidation products
      from the reactions of NO2 with isoprene and 1,3-cyclohexadiene were found to be
      mainly nitro compounds identified by FT-IR spectroscopy. Reaction mechanisms were
      proposed to account for the products observed. 

PMID- 24320546
TI  - A detailed gene expression study of the Miscanthus genus reveals changes in the
      transcriptome associated with the rejuvenation of spring rhizomes.
AB  - BACKGROUND: The Miscanthus genus of perennial C4 grasses contains promising
      biofuel crops for temperate climates. However, few genomic resources exist for
      Miscanthus, which limits understanding of its interesting biology and future
      genetic improvement. A comprehensive catalog of expressed sequences were
      generated from a variety of Miscanthus species and tissue types, with an emphasis
      on characterizing gene expression changes in spring compared to fall rhizomes.
      RESULTS: Illumina short read sequencing technology was used to produce
      transcriptome sequences from different tissues and organs during distinct
      developmental stages for multiple Miscanthus species, including Miscanthus
      sinensis, Miscanthus sacchariflorus, and their interspecific hybrid Miscanthus *
      giganteus. More than fifty billion base-pairs of Miscanthus transcript sequence
      were produced. Overall, 26,230 Sorghum gene models (i.e., ~ 96% of predicted
      Sorghum genes) had at least five Miscanthus reads mapped to them, suggesting that
      a large portion of the Miscanthus transcriptome is represented in this dataset.
      The Miscanthus * giganteus data was used to identify genes preferentially
      expressed in a single tissue, such as the spring rhizome, using Sorghum bicolor
      as a reference. Quantitative real-time PCR was used to verify examples of
      preferential expression predicted via RNA-Seq. Contiguous consensus transcript
      sequences were assembled for each species and annotated using InterProScan.
      Sequences from the assembled transcriptome were used to amplify genomic segments
      from a doubled haploid Miscanthus sinensis and from Miscanthus * giganteus to
      further disentangle the allelic and paralogous variations in genes. CONCLUSIONS:
      This large expressed sequence tag collection creates a valuable resource for the
      study of Miscanthus biology by providing detailed gene sequence information and
      tissue preferred expression patterns. We have successfully generated a database
      of transcriptome assemblies and demonstrated its use in the study of genes of
      interest. Analysis of gene expression profiles revealed biological pathways that
      exhibit altered regulation in spring compared to fall rhizomes, which are
      consistent with their different physiological functions. The expression profiles
      of the subterranean rhizome provides a better understanding of the biological
      activities of the underground stem structures that are essentials for
      perenniality and the storage or remobilization of carbon and nutrient resources.

PMID- 24320550
TI  - Population genomic analyses from low-coverage RAD-Seq data: a case study on the
      non-model cucurbit bottle gourd.
AB  - Restriction site-associated DNA sequencing (RAD-Seq), a next-generation
      sequencing-based genome 'complexity reduction' protocol, has been useful in
      population genomics in species with a reference genome. However, the application
      of this protocol to natural populations of genomically underinvestigated species,
      particularly under low-to-medium sequencing depth, has not been well justified.
      In this study, a Bayesian method was developed for calling genotypes from an F2
      population of bottle gourd [Lagenaria siceraria (Mol.) Standl.] to construct a
      high-density genetic map. Low-depth genome shotgun sequencing allowed the
      assembly of scaffolds/contigs comprising approximately 50% of the estimated
      genome, of which 922 were anchored for identifying syntenic regions between
      species. RAD-Seq genotyping of a natural population comprising 80 accessions
      identified 3226 single nuclear polymorphisms (SNPs), based on which two sub-gene
      pools were suggested for association with fruit shape. The two sub-gene pools
      were moderately differentiated, as reflected by the Hudson's F(ST) value of 0.14,
      and they represent regions on LG7 with strikingly elevated F(ST) values. Seven
      fold reduction in heterozygosity and two times increase in LD (r2) were observed
      in the same region for the round-fruited sub-gene pool. Outlier test suggested
      the locus LX3405 on LG7 to be a candidate site under selection. Comparative
      genomic analysis revealed that the cucumber genome region syntenic to the high
      FST island on LG7 harbors an ortholog of the tomato fruit shape gene OVATE. Our
      results point to a bright future of applying RAD-Seq to population genomic
      studies for non-model species even under low-to-medium sequencing efforts. The
      genomic resources provide valuable information for cucurbit genome research.

PMID- 24320549
TI  - Fluorescence and piezoresistive cantilever sensing of trinitrotoluene by an upper
      rim tetrabenzimidazole conjugate of calix[4]arene and delineation of the features
      of the complex by molecular dynamics.
AB  - A new benzimidazole-functionalized calix[4]arene receptor (R) was synthesized and
      characterized. The receptor R shows better selectivity toward trinitrotoluene
      (TNT) compared to the other nitro explosives in solution, which also retains its
      effectiveness for solid-phase detection. The chemical interactions of the
      molecule with different nitro explosive analytes were studied by fluorescence
      spectroscopy and by a molecular dynamics approach. The molecular dynamics studies
      show a 1:3 complex between R and TNT, and hence high sensitivity was imparted by
      fluorescence studies. The detection of explosive vapors in ambient conditions was
      tested by using a sensitive coating layer of R on an SU-8/CB-based piezoresistive
      cantilever surface. The developed device showed large sensitivity toward TNT
      compared to cyclotrimethylenetrinitramine (RDX) and pentaerythritol tetranitrate
      (PETN) in the solid state at their respective vapor pressures at room
      temperature. The detection sensitivity of the device was estimated to be 35 mV
      for TNT at ambient conditions. Moreover, the sensor does not show a response when
      exposed to humidity. These results demonstrate that R can be used as one of the
      coating materials for a cantilever for the detection of TNT using
      piezoresistivity measurement. R can also detect the explosives in solution with
      high sensitivity and selectivity by fluorescence spectroscopy. 

PMID- 24320551
TI  - Comparison of single 1-day-old chick vaccination using a Newcastle disease virus
      vector with a prime/boost vaccination scheme against a highly pathogenic avian
      influenza H5N1 challenge.
AB  - Avian influenza (AI) vaccines should be used as part of a whole comprehensive AI
      control programme. Vectored vaccines based on Newcastle disease virus (NDV) are
      very promising, but are so far licensed in only a few countries. In the present
      study, the immunogenicity and protection against a highly pathogenic H5N1
      influenza challenge were evaluated after vaccination with an enterotropic NDV
      vector expressing an H5 haemagglutinin (rNDV-H5) in 1-day-old specific pathogen
      free chickens inoculated once, twice or once followed by a heterologous boost
      with an inactivated H5N9 vaccine (iH5N9). The heterologous prime/boost rNDV
      H5/iH5N9 combination afforded the best level of protection against the H5N1
      challenge performed at 6 weeks of age. Two rNDV-H5 administrations conferred a
      good level of protection after challenge, although only a cellular H5-specific
      response could be detected. Interestingly, a single administration of rNDV-H5
      gave the same level of protection as the double administration but without any
      detectable H5-specific immune response. In contrast to AI immunity, a high
      humoral, mucosal and cellular NDV-specific immunity could be detected up to 6
      weeks post vaccination after using the three different vaccination schedules. NDV
      specific mucosal and cellular immune responses were slightly higher after double
      rNDV-H5 vaccination when compared with single inoculation. Finally, the
      heterologous prime/boost rNDV-H5/iH5N9 combination induced a broader detectable
      immunity including systemic, mucosal and cellular AI and NDV-specific responses. 

PMID- 24320552
TI  - Mathematical modeling of the in vitro hepatic disposition of mycophenolic acid
      and its glucuronide in sandwich-cultured human hepatocytes.
AB  - In recent years, it has become increasingly important to test the safety of
      circulating metabolites of novel drugs as part of drug discovery and development
      programs. Accordingly, it is essential to develop suitable methods for
      identifying the major metabolites and their disposition in animal species and in
      humans. Mycophenolic acid (MPA), a selective inosine-5'-monophosphate
      dehydrogenase (IMPDH) inhibitor, is metabolized by glucuronidation and
      enterohepatic circulation of MPA-glucuronides is an important factor in the
      continuous systemic exposure of MPA. In humans, about 90% of the administered MPA
      dose is finally excreted as MPA phenyl-glucuronide (MPAG) in urine. Notably, the
      plasma concentration of MPAG is much higher than that of MPA. These factors
      suggest that, after its formation in hepatocytes, MPAG is excreted into bile and
      is also transported across the basolateral membrane to enter the circulation. In
      the present study, we performed metabolic/hepatobiliary transport studies of MPA
      and MPAG using sandwich-cultured human hepatocytes (SCHH) and constructed
      mathematical models of their hepatic disposition. We also performed vesicular
      transport studies to identify which human multidrug resistance-associated
      proteins (MRPs) are involved in the transport of MPAG from hepatocytes. MPAG was
      a preferred substrate for the biliary excretion transporter MRP2 and the hepatic
      basolateral transporters MRP3 and MRP4 in conventional and
      metabolic/hepatobiliary transport studies using SCHH and vesicular transport
      studies using human MRP-expressing membrane vesicles. The resulting mathematical
      model suggested that the basolateral transport plays an important role in the
      hepatic disposition of MPAG formed in hepatocytes. Our findings suggest that
      mathematical modeling of metabolic/hepatobiliary transport studies using SCH will
      provide useful information for determining the fate of metabolites formed in
      hepatocytes. 

PMID- 24320553
TI  - Noninvasive imaging for the diagnosis and prognosis of pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is a major cause of morbidity and mortality, but it
      often presents with nonspecific symptoms, thereby delaying diagnosis and
      treatment. While invasive cardiac catheterization is essential to confirm the
      diagnosis, patients with breathlessness are commonly encountered in clinical
      practice creating a demand for noninvasive screening methods. Preliminary
      investigations such as the electrocardiogram and chest radiograph lack
      sensitivity even in advanced cases. Echocardiography is used to screen patients;
      however, over-reliance on a single estimation of pulmonary artery systolic
      pressure is unwise, instead multiple parameters should be assessed. Once a
      diagnosis of PH is made, radionuclide imaging should be performed to exclude
      chronic thromboembolic disease, and computed tomography is vital for eliminating
      parenchymal lung disease as a potential etiology. Currently, the primary
      contribution of cardiac MRI is the accurate assessment of right ventricular size
      and function. In this respect, cardiac MRI may be supportive during diagnosis of
      PH, but the main importance of this is in defining prognosis although new outcome
      variables are anticipated. 

PMID- 24320554
TI  - Responses to tonic heat pain in the ongoing EEG under conditions of controlled
      attention.
AB  - To confirm the existence of an ongoing electroencephalogram (EEG) pattern that is
      truly suggestive of pain, tonic heat pain was induced by small heat pulses at 1 
      degrees C above the pain threshold and compared to slightly less intense tonic
      non-painful heat pulses at 1  degrees C below the pain threshold. Twenty healthy
      subjects rated the sensation intensity during thermal stimulation. Possible
      confounding effects of attention were thoroughly controlled for by testing in
      four conditions: (1) focus of attention directed ipsilateral or (2) contralateral
      to the side of the stimulation, (3) control without a side preference, and (4) no
      control of attention at all. EEG was recorded via eight leads according to the
      10/20 convention. Absolute power was computed for the frequency bands delta (0.5
      4 Hz), theta (4-8 Hz), alpha1 (8-11 Hz), alpha2 (11-14 Hz), beta1 (14-25 Hz), and
      beta2 (25-35 Hz). Ratings were clearly distinct between the heat and pain
      conditions and suggestive for heat and pain sensations. Manipulation of attention
      proved to be successful by producing effects on the ratings and on the EEG
      activity (with lower ratings and lower EEG activity (theta, beta1, 2) over
      central areas for side-focused attention). During pain stimulation, lower central
      alpha1 and alpha2 activity and higher right-parietal and right-occipital delta
      power were observed compared to heat stimulation. This EEG pattern was not
      influenced by the manipulation of attention. Since the two types of stimuli
      (pain, heat) were subjectively felt differently although stimulation intensities
      were nearby, we conclude that this EEG pattern is clearly suggestive of pain.

PMID- 24320555
TI  - Rapid evolution of an invasive weed.
AB  - Trade-offs between performance and the ability to tolerate abiotic and biotic
      stress have been suggested to explain both the success of invasive species and
      phenotypic differentiation between native and invasive populations. It is
      critical to sample broadly across both ranges and to account for latitudinal
      clines and maternal effects when testing this premise. Wild-collected Centaurea
      diffusa seeds were grown in benign and stressful conditions (drought, flooding,
      nutrient stress and simulated herbivory), to evaluate whether native and
      introduced individuals differ in performance or life history phenotypes. A second
      experiment used glasshouse-grown seeds to evaluate whether patterns remain
      comparable when maternal environment is consistent. Many traits differed between
      ranges, and in all cases but one, invasive individuals grew larger, performed
      better, or matured later. No trade-off in performance with herbivore defense was
      evident. Invasive populations may have been released from a trade-off between
      growth and drought tolerance apparent in the native range. Larger individuals
      with delayed maturity and greater reproductive potential have evolved in invasive
      populations, a pattern evident across broad population sampling, and after
      latitude and maternal environment were considered. Release from abiotic stress
      tolerance trade-offs may be important for the invasion success of Centaurea
      diffusa. 

PMID- 24320556
TI  - The use of signal analyses of ventricular tachycardia electrograms to predict the
      response of antitachycardia pacing in patients with implantable cardioverter
      defibrillators.
AB  - INTRODUCTION: Antitachycardia pacing (ATP), a quick, painless, and effective
      therapy available in implantable cardioverter-defibrillators (ICDs), can
      terminate most, but not all, sustained ventricular tachycardias (VTs). This study
      investigated the possible ventricular electrogram (EGM) factors for predicting
      the effectiveness of ATP therapy from ICD recordings. METHODS AND RESULTS: In
      this study, we analyzed 113 EGMs of VT episodes acquired from 20 patients who
      received ATP or shock to terminate tachyarrhythmias during follow-up after ICD
      implantations. The relationship between the outcome of ATP and VT EGM features
      (such as voltage, width, cycle length, and beat-to-beat morphologic variation)
      was investigated. The divergence (beat-to-beat morphologic variation) of the VT
      EGMs was determined by calculating the total deviation of all EGMs away from the
      average template after all VT EMGs were aligned. In total, 72 (63.7%) successful
      (Group I) and 41 (36.3%) unsuccessful (Group II) ATP therapy episodes were
      analyzed. The mean amplitude, cycle length, and EGM width were similar between
      these 2 groups (P > 0.05). A multivariate analysis demonstrated that the only
      predictor of successful ATP was the divergence among the VT EGMs (0.56 +/- 0.32
      vs 1.07 +/- 0.64, P < 0.001, for Groups 1 and 2, respectively). The optimal
      cutoff value for determining a successful ATP therapy was 0.73 (with an area
      under the curve of 0.769, sensitivity of 81.9% [95% CI = 71.1-90.0], and
      specificity of 65.9% [95% CI = 49.4-79.9], P < 0.0001). CONCLUSION: Signal
      analyses from stored EGMs of VT can predict the response of ATP therapy in
      patients with ICD implantations. A lesser ventricular beat-to-beat morphologic
      variation in the intracardiac recordings from ICDs correlated with a higher
      probability of a successful ATP.

PMID- 24320557
TI  - Support curvature and conformational freedom control chemical reactivity of
      immobilized species.
AB  - We show that bimolecular reactions between species confined to the surfaces of
      nanoparticles can be manipulated by the nature of the linker, as well as by the
      curvature of the underlying particles. 

PMID- 24320558
TI  - Lymphoma-associated skin cancer: incidence, natural history, and clinical
      management.
AB  - The link between immunosuppression and skin cancer has been well described. The
      two most common situations involving immunosuppression-associated skin cancer are
      solid organ transplantation and non-Hodgkin lymphoma (NHL), including chronic
      lymphocytic leukemia (CLL). Patients with lymphoma are more likely to have
      development of a secondary malignancy, with skin cancer being the most common.
      The most common types of skin cancer in patients with NHL/CLL include melanoma,
      squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Many
      skin cancers demonstrate increased aggressiveness in patients with NHL/CLL and
      are associated with higher recurrence rates, increased regional metastasis, and
      death secondary to skin cancer metastases. This review delineates the current
      research regarding the relationship between NHL/CLL and cutaneous malignancy.
      Immunosuppressed patients with skin cancer should be treated promptly and
      aggressively to decrease recurrence and metastases. Regular skin self
      examinations, dermatologic examinations, sun-protective habits, and education may
      prove beneficial in this high-risk patient population. 

PMID- 24320559
TI  - Interlaboratory comparison of a general method to screen foods for pesticides
      using QuEChERs extraction with high performance liquid chromatography and high
      resolution mass spectrometry.
AB  - An interlaboratory comparison of a multipesticide residue analytical method is
      reported. The goal of the comparison was to evaluate the potential for liquid
      chromatography/high resolution mass spectrometry along with a specific automated
      screening procedure to allow the determination of the presence or absence of a
      set of targeted compounds without additional manual review. The method utilized
      an off the shelf QuEChERs based extraction followed by analysis with an orbitrap
      mass spectrometer with the data evaluated by ToxID. The method was tested at
      three laboratories, with three produce matrices (spinach, carrots, and oranges),
      and three levels of spiked pesticides with all analyses in triplicate. A series
      of 247 compounds were tested, and it was found that the three laboratories
      produced consistent data; however, manual review was still necessary. The data
      was shown to have no false negatives for 211 compounds in the three produce
      matrixes at 200 ppb. Of these 211 compounds, 189 had no false negatives at 50
      ppb, and 129 had no false negatives at 10 ppb. The HRMS method was shown to be
      robust with similar data being achieved by all three laboratories and detectable
      concentrations only slightly above the range shown for triple quadrupole MS/MS. 

PMID- 24320560
TI  - Tramadol versus fentanyl during propofol-based deep sedation for uterine
      dilatation and curettage: a prospective study.
AB  - AIM: Dilatation and curettage (D&C) is a common day-care procedure in obstetrics
      and gynecology, with patients discharged after a brief hospital stay on the same
      day of the surgery. Although it has a short duration, severe pain occurs during
      the procedure. Therefore, this surgical procedure requires an anesthetic to
      provide adequate analgesia, rapid onset, and rapid recovery. The main objective
      of the present study was to compare the analgesic effectiveness and safety of
      tramadol with those of fentanyl during D&C. METHODS: The study comprised 100
      women with American Society of Anesthesiologists classification I-II who were
      scheduled for a D&C procedure. Baseline anesthesia was maintained with 1 mg/kg
      propofol, and the patients were then randomly allocated to receive tramadol 1
      mg/kg (Group T, n = 50) or fentanyl 1 MUg/kg (Group F, n = 50). Hemodynamic
      variables, sedation, pain, the Aldrete recovery score, and side-effects were
      recorded. RESULTS: SpO2 levels in Group F in the 5th min and at the end of the
      procedure were significantly lower than those in Group T (P = 0.024 and 0.021,
      respectively). CONCLUSION: Tramadol provides similar analgesic efficacy to
      fentanyl. Furthermore, tramadol may provide better respiratory stability in
      patients undergoing a D&C procedure.

PMID- 24320561
TI  - The chaperonin CCT interacts with and mediates the correct folding and activity
      of three subunits of translation initiation factor eIF3: b, i and h.
AB  - eIF3 (eukaryotic initiation factor 3) is the largest and most complex eukaryotic
      mRNA translation factor in terms of the number of protein components or subunits.
      In mammals, eIF3 is composed of 13 different polypeptide subunits, of which five,
      i.e. a, b, c, g and i, are conserved and essential in vivo from yeasts to
      mammals. In the present study, we show that the eukaryotic cytosolic chaperonin
      CCT [chaperonin containing TCP-1 (tailless complex polypeptide 1)] binds to newly
      synthesized eIF3b and promotes the correct folding of eIF3h and eIF3i.
      Interestingly, overexpression of these last two subunits is associated with
      enhanced translation of specific mRNAs over and above the general enhancement of
      global translation. In agreement with this, our data show that, as CCT is
      required for the correct folding of eIF3h and eIF3i subunits, it indirectly
      influences gene expression with eIF3i overexpression enhancing both cap- and IRES
      (internal ribosome entry segment)-dependent translation initiation, whereas eIF3h
      overexpression selectively increases IRES-dependent translation initiation.
      Importantly, these studies demonstrate the requirement of the chaperonin
      machinery for the correct folding of essential components of the translational
      machinery and provide further evidence of the close interplay between the cell
      environment, cell signalling, cell proliferation, the chaperone machinery and
      translational apparatus.

PMID- 24320563
TI  - Stem cells in the canine pituitary gland and in pituitary adenomas.
AB  - Cushing's disease (CD) or pituitary-dependent hypercortisolism is a common
      endocrinopathy in dogs, with an estimated prevalence of 1 or 2 in 1000 dogs per
      year. It is caused by an adrenocorticotropic hormone secreting adenoma in the
      pars distalis or pars intermedia of the pituitary gland. The pituitary gland is a
      small endocrine gland located in the pituitary fossa. In the postnatal
      individual, the hypothalamus-pituitary axis plays a central role in maintaining
      homeostatic functions, like control of metabolism, reproduction, and growth. Stem
      cells are suggested to play a role in the homeostatic adaptations of the adult
      pituitary gland, such as the rapid specific cell-type expansion in response to
      pregnancy or lactation. Several cell populations have been suggested as pituitary
      stem cells, such as Side Population cells and cells expressing Sox2 or Nestin.
      These cell populations are discussed in this review. Also, stem and progenitor
      cells are thought to play a role in pituitary tumorigenesis, such as the
      development of pituitary adenomas in dogs. There are limited reports on the role
      of stem cells in pituitary adenomas, especially in dogs. Further studies are
      needed to identify and characterize this cell population and to develop specific
      cell targeting therapeutic strategies as a new way of treating canine CD. 

PMID- 24320562
TI  - A selective sweep in a microsporidian parasite Nosema-tolerant honeybee
      population, Apis mellifera.
AB  - Nosema is a microsporidian parasite of the honeybee, which infects the epithelial
      cells of the gut. In Denmark, honeybee colonies have been selectively bred for
      the absence of Nosema over decades, resulting in a breeding line that is tolerant
      toward Nosema infections. As the tolerance toward the Nosema infection is a
      result of artificial selection, we screened chromosome 14 for a selective sweep
      with microsatellite markers, where a major quantitative trait locus (QTL) had
      been identified to be involved in the reduction in Nosema spores in the
      honeybees. By comparing the genetic variability of 10 colonies of the selected
      honeybee strain with a population sample from 22 unselected colonies, a selective
      sweep was revealed within the previously identified QTL region. The genetic
      variability of the swept loci was not only reduced in relation to the flanking
      markers on chromosome 14 within the selected strain but also significantly
      reduced compared with the same region in the unselected honeybees. This confirmed
      the results of the previous QTL mapping for reduced Nosema infections. The
      success of the selective breeding may have driven the selective sweep found in
      our study. 

PMID- 24320564
TI  - The contribution of glycemic control to impaired growth during puberty in young
      people with type 1 diabetes and microalbuminuria.
AB  - BACKGROUND: In adults with type 1 diabetes (T1D), short stature has been
      associated with risk for cardiovascular disease and nephropathy. However, there
      are no available data on the potential relationship between growth patterns
      during puberty and the development of vascular complications. Our aim was to
      assess whether pubertal growth is impaired in young people with T1D who develop
      microalbuminuria (MA). METHODS: Repeated height measurements performed during
      adolescence were available for 206 young people (107 boys) with T1D followed in
      the Oxford Regional Prospective Study. Longitudinal data on albumin-creatinine
      ratios and hemoglobin A1c (HbA1c) were also collected from the study
      participants. Height standard deviations score (SDS) was compared between
      subjects with (MA+; n = 66) and without MA (MA-; n = 140). RESULTS: In the group
      as a whole, mean [95% CI] height SDS progressively declined during puberty, from
      0.145 [0.015; 0.274] to -0.003 [-0.145; 0.138], p < 0.001. However, the decline
      in height SDS was significantly different between the MA+ and MA- groups (p =
      0.023), with a mean difference in final height of 4.29 [1.87; 6.72] cm, p =
      0.001. Final height was inversely associated with MA (HR [95%CI]: 0.942 [0.908;
      0.979], p = 0.002), although this association was no longer significant after
      adjusting for HbA1c, which was higher in the MA+ group. CONCLUSION: In this
      study, we found a significant impairment in growth during puberty in young people
      with T1D, particularly in those developing MA. Poor glycemic control as well as
      other genetic or environmental factors could explain these associations.

PMID- 24320565
TI  - P-wave abnormality predicts recurrence of atrial fibrillation after electrical
      cardioversion: a prospective study.
AB  - BACKGROUND: Maintenance of atrial fibrillation (AF) is related to atrial
      electrical inhomogeneity and resultant chaotic reentry. Our aim was to test the
      hypothesis that abnormalities of P morphology on the surface electrocardiogram
      (ECG) predict recurrent AF following electrical cardioversion (ECV). METHODS: A
      12-lead ECG was recorded after ECV for persistent AF in 77 patients (51 men, 65
      +/- 10 years) and repeated 1 month later. P-wave duration was obtained in each
      lead using blinded on-screen measurement. Maximum P-wave duration (P-max) was
      defined as the longest measurable P-wave duration in any lead. P-wave dispersion
      (PWd) was calculated as the maximum-minimum P-wave duration. RESULTS: One month
      after ECV, 29 (38%) patients maintained sinus rhythm. Compared with the sinus
      rhythm group, those with recurrent AF had significantly greater PWd (66 +/- 19 vs
      57 +/- 16 ms, P = 0.024) and included more patients with P-max >=142 ms (65% vs
      38%, P = 0.023). Using a cutoff of >=62 ms for PWd and >=142 ms for P-max, both
      indices had similar predictive value (sensitivity 66.7 and 64.6%, specificity
      58.6 and 62.1%, respectively). In multiple regression analysis, including
      established clinical predictors, P-max >=142 ms was the only independent
      predictor of AF recurrence (P = 0.025). CONCLUSION: A prolonged P-wave duration
      measured by 12-lead ECG predicts recurrent AF within 1 month after ECV.

PMID- 24320566
TI  - Effect of local structure distortion on superconductivity in Mg- and F-codoped
      LaOBiS2.
AB  - La1-xMgxO1-2xF2xBiS2 (x = 0.1-0.35) were synthesized, and their superconductive
      properties were investigated. The superconducting transition temperature (Tc)
      increased below the codoping level (x <= 0.25). La1-xMgxOBiS2 (x = 0-0.2) and La1
      xMgxO0.6F0.4BiS2 (x = 0.1-0.3) were further prepared to explore the effect of
      Mg(2+). We found that the introduction of Mg(2+) and F(-) leads to local
      structure distortion. Larger distortion is beneficial for superconductivity in
      LaOBiS2, which was further confirmed by the results in La1-xCaxO1-2xF2xBiS2 (x =
      0.2, 0.3). 

PMID- 24320567
TI  - Complete mitochondrial genome of the entomopathogenic fungus Beauveria
      pseudobassiana (Ascomycota, Cordycipitaceae).
AB  - The complete mitochondrial genome of the entomopathogenic fungus Beauveria
      pseudobassiana (Ascomycota, Cordycipitaceae) was determined and found to be
      28,006 bp in length. It encodes genes for 14 proteins, 2 ribosomal RNA subunits,
      25 transfer RNAs with the synteny identical to those of B. bassiana and B.
      brongniartii. The overall base composition is 36.7% A, 35.8% T, 15.3% C and 12.2%
      G with an AT content of 72.5%. Group-I introns were found in large rRNA gene
      (rnl) and cox2 gene that include rps3 gene and putative GIY-YIG homing
      endonuclease, respectively. The mitochondrial genome of B. pseudobassiana will
      contribute to the investigation of the phylogenetic relationship, taxonomic
      resolution and biogeography of Beauveria.

PMID- 24320568
TI  - A case for APRIL/BLyS directed therapy not eosinophil directed therapy for
      alloantibody elimination.

PMID- 24320570
TI  - What an understanding of the dynamics of gossip has to teach about group dynamics
      and group leadership.
AB  - Although what transpires in group therapy is not gossip per se-except perhaps
      when absent or former members are discussed-listening to group interaction
      through an understanding of the dynamics of gossip can contribute to a greater
      appreciation of group dynamics and group leadership as well as enlarge
      therapeutic space. After examining the interpersonal dynamics of gossip, this
      paper discusses six ways in which an understanding of these dynamics can inform
      group leadership and shed light on group psychotherapy. Central features of
      gossip that appear in group interactions are explored: These include projection,
      displacement, self-esteem regulation, clarification of motivation, unself
      consciousness, social comparison and bonding, avoidance of psychic pain, and
      making the ego-syntonic dystonic. The lively use of imagination in the mature
      phase of group therapy is conceived of as the time when the darker side of human
      nature-imagined gossip harnessed for therapeutic purposes-can be welcomed in and
      processed in a kind, playful, and compassionate manner.

PMID- 24320571
TI  - Trauma group therapy: the role of attachment and therapeutic alliance.
AB  - Attachment has increasingly been identified as central to therapy process and
      outcome. Attachment theory proposes that an individual's prior interactions with
      attachment figures develop into templates that will guide the way they form
      connections and perceive their relationships with others. This study examined
      clients' ratings of their relationship with the therapist as well as their
      ratings of group climate at multiple discrete points during treatment. These
      variables were examined in relation to attachment classification prior to
      therapy. Participants were 62 women attending the Women Recovering from Abuse
      Program (WRAP), a primarily group-based day-treatment program for childhood
      interpersonal trauma, at Women's College Hospital in Toronto, Ontario, Canada.
      Results demonstrated that clients' perceptions of relationships in group therapy
      varied as a function of attachment classification.

PMID- 24320572
TI  - Consciousness-raising in a gender conflict group.
AB  - This article describes the main processes and themes in consciousness-raising
      gender conflict groups for undergraduate students who study in parallel a course
      on gender and psychology. The main theme of the course is that gender is a
      classification system that influences individuals, interactions between
      individuals, and social institutions. The aim of the groups is to provide
      students with a safe environment to discuss their thoughts and feelings following
      the encounter of these ideas. Group leading is based on a combination of
      principles derived from consciousness-raising groups from the 1970s and a model
      for working with groups in conflict.

PMID- 24320573
TI  - A psychodynamic approach: commentary on "consciousness-raising in a gender
      conflict group".

PMID- 24320574
TI  - The personal is political: gender stereotypes in the unconscious life of groups:
      commentary on "consciousness-raising in a gender conflict group".

PMID- 24320575
TI  - Response to Nina K. Thomas and J. Scott Rutan: is the personal political? And who
      benefits from believing it is not?

PMID- 24320576
TI  - Excitement in shame: the price we pay.
AB  - This paper explores the role of excitement in shame, extending the theoretical
      underpinnings of my work (Aledort, 2002, 2003, 2008, 2009) on narcissism and the
      omnipotent child syndrome. Shame, excitement, and early narcissistic self-states
      are complexly intermingled, each influencing the other. Empathy alone is
      insufficient; the passion connected to shame can be easily hidden. Detailed case
      studies describe a model for working with the excitement in shame, how it
      functions, and how it gets resolved.

PMID- 24320577
TI  - What are we hiding and whom are we hiding from?

PMID- 24320579
TI  - Body-awareness and movement-based group treatments for stress.

PMID- 24320582
TI  - Letter to the editor.

PMID- 24320585
TI  - [Smoking and breast cancer].
AB  - BACKGROUND: Investigation of the relationship between smoking and breast cancer
      risk did not show a consensus in results - some studies described smoking as a
      risk factor, while others found its effects protective. PURPOSE: The newest
      studies explain these differences by the genetic polymorphism. Cigarette smoke
      contains at least 20 chemical carcinogens, which are deposited and metabolically
      activated in the breast and surrounding adipose tissues. The substances are
      further detected in the nipple discharge or as smoking  specific DNA adducts in
      breast tissue. Several studies postulate significantly higher risk of breast
      cancer among women who started smoking at an early age and/ or before their first
      delivery. Some studies from Japan, China, California have shown that longterm
      exposure to passive smoking could significantly increase the risk of breast
      cancer in never smokers, while other scientist reject the evidence of this
      association as inconsistent. A possible protective effect of smoking on the
      incidence of breast cancer is explained by antiestrogenic activity of smoking,
      namely nicotine. CONCLUSION: Smoking may play a role in the breast cancer
      incidence. Due to a wide spectrum of harmful effects of smoking, and with regards
      to the worse prognosis of breast cancer among smoking patients, the common
      recommendations for cancer prevention are similarly plausible in case of breast
      cancer - no  smoking, no alcohol, fruit and vegetable consumption, physical
      activity and body weight control.

PMID- 24320586
TI  - [Radiobiological pitfalls of new techniques in radiotherapy].
AB  - Radiotherapy techniques in the last decade evolved to the stage where the
      potential dose distribution significantly differs from earlier practices.
      Rotational IMRT, robotic radiotherapy or proton radiotherapy enables extremely
      precise dose delivery to target volumes, on the other hand, these techniques can
      yield a number of problems. As for photon radiotherapy, this concerns primarily
      the effect of large volume irradiation with doses of 0.10.5 Gy. In this range,
      the hypersensitivity to low doses and the bystander effect may play an important
      role. Proton therapy is upredictable in its radiobiological effect at the end of
      the Bragg curve and there is also uncertainty about the peaks exact location.
      These effects should be taken into account when choosing among the irradiation
      techniques or when applying tolerance doses to critical organs in clinical
      practice, especially in younger patients with long survival expectation.

PMID- 24320587
TI  - [Oncogenic potential of papillomaviruses].
AB  - Papillomaviruses belong to a group of viruses with double-stranded DNA (dsDNA).
      These viruses are believed to induce benign as well as malignant tumour growth.
      Thanks to professor zur Hausen, the connection between the infection by human
      papillomaviruses (HPV) and cervix cancer was described in detail a few years ago.
      However, there exist certain types of HPV viruses, in which no association with
      malignancies was ever demonstrated. Hence, we can divide HPV into "high-risk"
      (HR) and "low-risk" (LR) group. Our work describes the life cycle of HPV,
      molecular mechanisms of oncogenesis and aims to compare HR HPV and LR HPV within
      these terms.

PMID- 24320588
TI  - [The assessment of quality of life of patients at oncological clinic - pilot
      study].
AB  - BACKGROUND: In oncological care the main emphasis should not be put only on
      prolonging a patients life, but also on its quality. The aim of the study was to
      assess the quality of life of patients hospitalized at the oncology clinic of the
      University Hospital of Ostrava (UHO), who exhausted all the anticancer treatment
      options. PATIENTS (SAMPLE) AND METHODS: In a pilot study the sample consisted of
      93 patients from the oncological clinic of UHO with Karnofsky score < 60. A
      questionnaire EORTC QOL C30 was used to evaluate the quality of life. RESULTS:
      The overall score of quality of life was 49%. Repeated measurement showed a
      significant decrease of the score to 37% (p < 0.001). Assessing the quality of
      life on a functioning scale, role functioning (47.3; 95% CI 42.6- 52.1) and
      social functioning (48.0; 95% CI 42.5- 53.5) were assessed the worst. When
      judging on a symptoms scale, patients reported the major problem was fatigue
      (48.8; 95% CI 44.8- 52.8) and pain (44.5; 95% CI 39.2- 48.8). Repeated
      measurement showed a statistically significant decrease in quality of life on the
      scale of functioning in all areas. On the symptoms scale there was similarly a
      decline of quality in fatigue, pain and breathlessness categories (p < 0.01).
      Furthermore, we observed a correlation between lower overall quality of life and
      a worse level of physical functions (r = 0.8047), social relationships (r =
      0.7796), fatigue (r = 0.8166) and pain intensity (r = 0.8282). CONCLUSION:
      Palliative care patients admitted to the oncology clinic perceive their quality
      of life as inferior. Home palliative care or a hospice appears to be a more
      suitable environment for the management of terminal care.

PMID- 24320589
TI  - [Five-year results of IMRT for prostate cancer - toxicity].
AB  - BACKGROUND: Intensity modulated radiotherapy (IMRT) plays a crucial role in the
      treatment of prostate cancer thanks to its capacity for healthy tissue sparing.
      This work reports on the acute and late toxicity rates among 233 patients treated
      with high-dose IMRT. MATERIAL AND METHODS: From June 2003 to December 2007, 233
      men with clinically localized prostate cancer underwent radical radiotherapy. One
      hundred sixty patients were treated with IMRT to the prostate and the base of
      seminal vesicles to 78 Gy in 39 fractions, 73 patients underwent simultaneous
      integrated boost. Prescribed doses were 82 Gy and 73,8 Gy in 41 fractions to the
      prostate and seminal vesicles, respectively. Late toxicity was evaluated
      prospectively using a RTOG/FC-LENT score. RESULTS: Thirty patients (12.8%)
      experienced acute Grade 2 gastrointestinal (GI) toxicity. No acute Grade 3 or 4
      GI toxicity developed. Forty two patients (18.1%) experienced acute Grade 2
      genitourinary toxicity and 23 patients (9.9%) had Grade 3 GU toxicity. Grade 4
      Genitourinary toxicity was observed in nine (3.8%) patients, due to a need of
      short-term urinary catheterization. With a median follow-up of 49.2 months, the
      estimated 5-year cumulative incidence of Grade 2 gastrointestinal toxicity was
      22.4%. The estimated 5-year cumulative incidence of Grade 2 genitourinary
      toxicity was 17.7%. CONCLUSION: Intensity modulated radiotherapy enables dose
      escalation to 78-82 Gy with an acceptable toxicity.

PMID- 24320590
TI  - [Five-year results of IMRT for prostate cancer - tumor control].
AB  - BACKGROUND: Intensity-modulated radiation therapy (IMRT) is the method of choice
      in external-beam radiotherapy tolocalized prostate cancer. This work analyses
      five year results of IMRT with a dose of 78/82 Gy. PATIENTS AND METHODS: From
      June 2003 to December 2007, the IMRT technique was employed to treat 233 patients
      with T1-3 N0 M0 prostate cancer. It was supplemented by hormone therapy
      especially in high-risk patients. Two IMRT techniques were applied - IMRT with a
      dose of 78 Gy in 39 fractions to prostate and seminal vesicles (SV) (IMRT 78) and
      IMRT with simultaneous integrated 82 Gy boost to prostate concurrently with 73,8
      Gy in 41 fractions to SV (IMRT SIB 82). The IMRT 78 technique was used in 160
      patients (69%). Seventy-three (31%) patients with intermediate (IR) or high-risk
      (HR) prostate cancer without SV involvement were treated with IMRT SIB 82
      technique. The PSA relapse was defined as an increase in PSA of at least 2.0
      ng/mL above the nadir or in comparison to the value at the initiation of hormone
      therapy. Clinical relapse was defined as an occurence of distant metastases
      and/or local recurrence. RESULTS: The median follow-up of our patients'
      population was 4.3 years (range 0.6-8.9 years). The estimated 5-year PSA relapse
      free survival in low-risk (LR), IR and HR patients was 86%, 89% and 83%,
      respectively (p = NS). In a multivariate analysis, Gleason score (GS) 8-10 was
      associated with significantly higher risk of PSA relapse (RR 2.76), while higher
      age at the time of diagnosis significantly decreased the PSA relapse risk (RR
      0.94). The estimated 5-year clinical relapse-free survival in LR, IR and HR
      patients was 100%, 99% and 95%, respectively (p = NS). In a univariate analysis,
      both GS and PSA had a significant impact on the 5-year clinical relapse-free
      survival - GS 2-7 97 % vs GS 8-10 88 % (p = 0.03), PSA 20 98 % vs PSA > 20 85 %
      (p < 0.01). CONCLUSION: Treatment of localized prostate cancer using IMRT with a
      dose 78/82 Gy yielded an excellent 5-year tumour control with a risk of clinical
      relapse being less than 5%.

PMID- 24320591
TI  - Bilateral germ-cell testicular cancer - long-term experience.
AB  - BACKGROUND: Germ cell testicular cancer (TC) patients have an increased risk of
      developing a contralateral TC. This paper presents a retrospective analysis of
      patients with bilateral TC from a database of a single center and aims to
      highlight the need for an individual approach. MATERIAL AND METHODS: In the study
      period from January 1970 to June 2013, a total of 1,438 patients with primary TC
      were diagnosed. The group comprised of 1,370 patients with unilateral TC and 68
      patients with bilateral TC. Bilateral TC patients were evaluated regarding the
      age at presentation and the histology of tumor and then compared with the group
      of patients with unilate-ral TC. RESULTS: The mean age of the patients with
      unilateral TC was 31.7 years. This group of patients consisted of 408 patients
      with seminoma and 962 patients with non-seminomatous TC. The group of 68 patients
      with bilateral TC involved 63 patients with metachronous disease and five
      patients who developed TCs simultaneously. The mean age at diagnosis of primary
      tumor in patients with metachronous bilateral TC (25.8 years) was significantly
      earlier in comparison to patients with unilateral disease. Among 24 patients with
      seminoma there were 17 patients who subsequently developed a second malignancy of
      an identical histological type. In the group of 39 patients with initial non
      seminomatous TC there were 15 patients with discordant histology of the second
      tumor. In the metachronous disease group, patients with primary seminoma were
      significantly older than those with initial non-seminomas. CONCLUSIONS: All
      patients with unilateral TC have an increased risk of developing a contralateral
      TC, years and even decades after the initial diagnosis. Management of subsequent
      TC should be individualized for each patient according to the histology and
      clinical stage of the primary tumor, as well as the therapeutic strategy applied
      initially. The further management should involve a long-term follow-up and life
      long testosterone substitution.

PMID- 24320592
TI  - [OPERa Study].
AB  - BACKGROUND: On the whole, most European and international guidelines recommend
      prophylactic use of granulocyte-colony stimulating factors (G-CSFs) when the risk
      of chemotherapy-induced febrile neutropenia (FN) in cancer patients exceeds 20%.
      In patients treated with intermediate-risk chemotherapy regimens the recent EORTC
      guidelines recommend to consider supplementary patient-related adverse risk
      factors such as elderly age ( 65 years) prior to administrating each cycle of
      chemotherapy. The primary objective of our study is to describe the most
      important FN risk factors that underlie the use of pegfilgrastim PP in daily
      practice in the Czech Republic; secon-dary endpoints include FN incidence,
      chemotherapy dose intensity, anti-infective agents admini-stration,
      hospitalization length and safety of chemotherapy regimens. PATIENTS AND METHODS:
      This prospective, multicenter, non-interventional study enrolled patients
      receiving a chemotherapy with high FN risk ( 20% according to EORTC guidelines)
      based on investigators' assessment. RESULTS: Data were collected on a total of
      333 patients treated for breast cancer (69%), lymphoma (20%), ovarian (5%), lung
      (4%) and testicular cancer (1%). The most frequent indications for G-CSF
      prophylaxis were myelotoxic chemotherapy regimen (96%), elderly age (36%),
      advanced stage disease (35%), female gender (30%), cancer type (15%) and previous
      FN episode (12%). The overall FN incidence was 3% in patients receiving primary
      pegfilgrastim prophylaxis (n = 210) and 12% in patients with no pegfilgrastim PP
      (n = 123). CONCLUSION: The myelotoxicity of a chemotherapeutic regimen was the
      most significant FN risk factor identified by the inquired physicians. The second
      most compelling FN risk factor was elderly age and advanced stage disease. FN
      incidence in patients who received pegfilgrastim PP was relatively low in
      comparison to the commonly expected FN incidence in a population of patients
      receiving a chemotherapy regimen with high risk of FN.

PMID- 24320593
TI  - [Syndrome of vena cava obstruction in oncology].
AB  - BACKGROUND: Superior vena cava syndrome (SVCO) is caused by compression of
      superior vena cava and restriction of blood flow to the heart. The most common
      underlying condition in cancer patients is lung cancer or other malignancy
      expanding in the upper mediastinum. SVCO belongs to oncological emergencies and
      requires a prompt dia-gnostic work up and treatment. CASE 1: A 79year old man
      with a history of right sided stage IIIB nonsmall cell lung cancer, after two
      cycles of chemotherapy, was admitted to hospital with clinical signs of SVCO. The
      initial radiotherapy brought no relief of symptoms and due to deterioration of
      patients status during the treatment we proceeded to self expanding caval stent
      insertion. This was followed by immediate resolution of SVCO symptoms. CASE 2: In
      the second case we describe a 56year old female with a newly dia-gnosed diffuse
      large B cell lymphoma who presented with SVCO symptoms when referred to our
      outpatient chemotherapy department. She had no history of previous treatment and
      she complained of a rapid face and eyelid edema and intractable cough in the last
      two days. CT scan revealed mediastinal mass compressing the superior vena cava.
      Urgent antilymphoma chemotherapy (RCHOP schedule) was commenced and yielded quick
      resolution of her symp-toms. CONCLUSION: Superior vena cava syndrome is a medical
      emergency in oncological patients usually caused by external compression of cava
      by lung cancer, lymphoma, other tumors, less frequently, from a thrombosis of
      indwelling central venous catheter. Multidiscip-linary cooperation among
      radiation and medical oncologists and interventional radiologists is needed in
      order to provide an early treatment without an undue delay.

PMID- 24320594
TI  - [Is preoperative bone scintigraphy in early stage of breast cancer T1N0 indicated
      and meaningful?].
AB  - In the Czech Republic bone scintigraphy has still been performed routinely as a
      part of preoperative staging examinations of early breast carcinomas, which had
      been in 42% diagnosed in the national breast cancer screening program. The
      incidence of synchronnous distant metastases was analysed for a subgroup of T1N0
      breast carcinomas using the database of the Czech National Cancer Registry. Out
      of 21,675 women with T1N0 breast carcinomas diagnosed in the decade of 2001-2010
      the potential occurence of various distant metastases (M1) was estimated in 147
      cases (0,68%). Since only approximately 40% of all distant metastases were
      skeletal (M1 OSS), the pro-bability of bone metastases in T1N0 breast cancer does
      not exceed 0,3-0,4%. Distant metastases were present in 0,5% in a subgroup of
      well and moderately differentiated carcinomas and up to 1,2% in poorly
      differentiated and anaplastic tumors, however, only a minor part (0,2% and 0,5%,
      respectively) involved bones. We conclude that preoperative bone scintigraphy is
      overused and undue in more than 99% of Czech women with early breast cancer T1N0.
      Skeletal scintigraphy as a staging procedure for small breast carcinoma T1N0 may
      perhaps be recommended only postoperatively and very selectively with regards to
      individual risk factors and symptomatology.

PMID- 24320596
TI  - Lichenoid cutaneous chronic GvHD following Blaschko lines.

PMID- 24320595
TI  - Automated workflow-based exploitation of pathway databases provides new insights
      into genetic associations of metabolite profiles.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified many common
      single nucleotide polymorphisms (SNPs) that associate with clinical phenotypes,
      but these SNPs usually explain just a small part of the heritability and have
      relatively modest effect sizes. In contrast, SNPs that associate with metabolite
      levels generally explain a higher percentage of the genetic variation and
      demonstrate larger effect sizes. Still, the discovery of SNPs associated with
      metabolite levels is challenging since testing all metabolites measured in
      typical metabolomics studies with all SNPs comes with a severe multiple testing
      penalty. We have developed an automated workflow approach that utilizes prior
      knowledge of biochemical pathways present in databases like KEGG and BioCyc to
      generate a smaller SNP set relevant to the metabolite. This paper explores the
      opportunities and challenges in the analysis of GWAS of metabolomic phenotypes
      and provides novel insights into the genetic basis of metabolic variation through
      the re-analysis of published GWAS datasets. RESULTS: Re-analysis of the published
      GWAS dataset from Illig et al. (Nature Genetics, 2010) using a pathway-based
      workflow (http://www.myexperiment.org/packs/319.html), confirmed previously
      identified hits and identified a new locus of human metabolic individuality,
      associating Aldehyde dehydrogenase family1 L1 (ALDH1L1) with serine/glycine
      ratios in blood. Replication in an independent GWAS dataset of phospholipids
      (Demirkan et al., PLoS Genetics, 2012) identified two novel loci supported by
      additional literature evidence: GPAM (Glycerol-3 phosphate acyltransferase) and
      CBS (Cystathionine beta-synthase). In addition, the workflow approach provided
      novel insight into the affected pathways and relevance of some of these gene
      metabolite pairs in disease development and progression. CONCLUSIONS: We
      demonstrate the utility of automated exploitation of background knowledge present
      in pathway databases for the analysis of GWAS datasets of metabolomic phenotypes.
      We report novel loci and potential biochemical mechanisms that contribute to our
      understanding of the genetic basis of metabolic variation and its relationship to
      disease development and progression.

PMID- 24320597
TI  - Boron bridging of rhamnogalacturonan-II, monitored by gel electrophoresis, occurs
      during polysaccharide synthesis and secretion but not post-secretion.
AB  - The cell-wall pectic domain rhamnogalacturonan-II (RG-II) is cross-linked via
      borate diester bridges, which influence the expansion, thickness and porosity of
      the wall. Previously, little was known about the mechanism or subcellular site of
      this cross-linking. Using polyacrylamide gel electrophoresis (PAGE) to separate
      monomeric from dimeric (boron-bridged) RG-II, we confirmed that Pb(2+) promotes
      H3 BO3 -dependent dimerisation in vitro. H3 BO3 concentrations as high as 50 mm
      did not prevent cross-linking. For in-vivo experiments, we successfully cultured
      'Paul's Scarlet' rose (Rosa sp.) cells in boron-free medium: their wall-bound
      pectin contained monomeric RG-II domains but no detectable dimers. Thus pectins
      containing RG-II domains can be held in the wall other than via boron bridges. Re
      addition of H3 BO3 to 3.3 MUm triggered a gradual appearance of RG-II dimer over
      24 h but without detectable loss of existing monomers, suggesting that only newly
      synthesised RG-II was amenable to boron bridging. In agreement with this, Rosa
      cultures whose polysaccharide biosynthetic machinery had been compromised (by
      carbon starvation, respiratory inhibitors, anaerobiosis, freezing or boiling)
      lost the ability to generate RG-II dimers. We conclude that RG-II normally
      becomes boron-bridged during synthesis or secretion but not post-secretion.
      Supporting this conclusion, exogenous [(3) H]RG-II was neither dimerised in the
      medium nor cross-linked to existing wall-associated RG-II domains when added to
      Rosa cultures. In conclusion, in cultured Rosa cells RG-II domains have a brief
      window of opportunity for boron-bridging intraprotoplasmically or during
      secretion, but secretion into the apoplast is a point of no return beyond which
      additional boron-bridging does not readily occur.

PMID- 24320598
TI  - Broiler lines divergently selected for digestive efficiency also differ in their
      susceptibility to colibacillosis.
AB  - Increasing feed efficiency of broiler chickens by selective breeding could lead
      to decreased feed cost and reduced environmental impact of poultry production. At
      INRA, two broiler chicken lines (D+/D-) were divergently selected for their
      digestive efficiency. Strong differences were shown between both lines for the
      anatomy and histology of the digestive tract, and for the intestinal microbiota
      composition. In the present study, we investigated whether this selection also
      had an effect on susceptibility to colibacillosis, which is one of the main
      causes of economic losses in poultry production. The broiler lines D+/D- were
      challenged with an avian pathogenic Escherichia coli strain. A first experiment
      was conducted to assess the 50% lethal dose by subcutaneous infection of
      hatchlings, whereas a second experiment reproduced colibacillosis by infecting
      air sacs of 23-day-old chicks. The 50% lethal dose was very low for both lines.
      However, the line with the higher digestive efficiency (D+) was the less
      susceptible to colibacillosis. This result is interesting for selection purposes
      and opens the way to integrative genetic studies of the interactions between
      digestion efficiency and resistance to colibacillosis. 

PMID- 24320600
TI  - Carbon-wrapped Fe3O4 nanoparticle films grown on nickel foam as binder-free
      anodes for high-rate and long-life lithium storage.
AB  - Carbon-wrapped Fe3O4 nanoparticle films on nickel foam were simply prepared by a
      hydrothermal synthesis with sucrose as a precursor of subsequent carbonization.
      The as-prepared samples were directly used as binder-free anodes for lithium-ion
      batteries which exhibited enhanced rate performance and excellent cyclability. A
      reversible capacity of 543 mA h g(-1) was delivered at a current density as high
      as 10 C after more than 2000 cycles. The superior electrochemical performance can
      be attributed to the formation of a thin carbon layer which constructs a 3D
      network structure enwrapping the nanosized Fe3O4 particles. Such an architecture
      can facilitate the electron transfer and accommodate the volume change of the
      active materials during discharge/charge cycling. 

PMID- 24320599
TI  - Synthesis, physicochemical characterization, and cytocompatibility of
      bioresorbable, dual-gelling injectable hydrogels.
AB  - Injectable, dual-gelling hydrogels were successfully developed through the
      combination of physical thermogellation at 37  degrees C and favorable
      amine:epoxy chemical cross-linking. Poly(N-isopropylacrylamide)-based
      thermogelling macromers with a hydrolyzable lactone ring and epoxy pendant groups
      and a biodegradable diamine-functionalized polyamidoamine cross-linker were
      synthesized, characterized, and combined to produce nonsyneresing and
      bioresorbable hydrogels. Differential scanning calorimetry and oscillatory
      rheometry demonstrated the rapid and dual-gelling nature of the hydrogel
      formation. The postgelation dimensional stability, swelling, and mechanical
      behavior of the hydrogel system were shown to be easily tuned in the synthesis
      and formulation stages. The leachable products were found to be cytocompatible
      under all conditions, while the degradation products demonstrated a dose- and
      time-dependent response due to solution osmolality. Preliminary encapsulation
      studies showed mesenchymal stem cell viability could be maintained for 7 days.
      The results suggest that injectable and thermally and chemically cross-linkable
      hydrogels are promising alternatives to prefabricated biomaterials for tissue
      engineering applications, particularly for cell delivery. 

PMID- 24320601
TI  - Storage capacity and vibration frequencies of guest molecules in CH4 and CO2
      hydrates by first-principles calculations.
AB  - Using first-principle calculations at B97-D/6-311++G(2d,2p) level, we
      systematically explore the gas capacity of five standard water cavities (5(12),
      4(3)5(6)6(3), 5(12)6(2), 5(12)6(4), and 5(12)6(8)) in clathrate hydrate and study
      the inclusion complexes to infer general trends in vibrational frequencies of
      guest molecules as a function of cage size and number of guest molecules. In
      addition, the Raman spectra of hydrates from CO2/CH4 gases are simulated. From
      our calculations, the maximum cage occupancy of the five considered cages (5(12),
      4(3)5(6)6(3), 5(12)6(2), 5(12)6(4), and 5(12)6(8)) is one, one, two, three, and
      seven for both CH4 and CO2 guest molecules, respectively. Meanwhile, the optimum
      cage occupancy are one, one, one, two, and four for CO2 molecules and one, one,
      two, three, and five for CH4 molecules, respectively. Both the C-H stretching
      frequency of CH4 and the C-O stretching frequency of CO2 gradually decrease as
      size of the water cages increases. Meanwhile, the C-H stretching frequency
      gradually increases as the amount of CH4 molecules in the water cavity (e.g.,
      5(12)6(8)) increases. 

PMID- 24320602
TI  - Vitamin D and multiple sclerosis: where do we go from here?
AB  - This article briefly introduces the basics of multiple sclerosis' (MS) clinical
      hallmarks and pathophysiology. Vitamin D is presented, including its metabolism
      and effects on the immune system. The epidemiological observations linking
      vitamin D to MS range from a half century old findings of latitude gradients and
      migrational risk patterns to modern, nested, case-control biobank studies. These
      observations show an association without doubt although causation has yet to be
      proven. Vitamin D as a treatment for MS is an emerging concept and both current
      and anticipated data will be covered. Lastly, we discuss future challenges, ideas
      on how to move from association to causation, and the prospect of primary
      prevention of this disabling disease. 

PMID- 24320603
TI  - Sex differences in cardiovascular and subjective stress reactions: prospective
      evidence in a realistic military setting.
AB  - Evidence points to heightened physiological arousal in response to acute stress
      exposure as both a prospective indicator and a core characteristic of
      posttraumatic stress disorder (PTSD). Because females may be at higher risk for
      PTSD development, it is important to evaluate sex differences in acute stress
      reactions. This study characterized sex differences in cardiovascular and
      subjective stress reactions among military survival trainees. One hundred and
      eighty-five military members (78% males) were studied before, during, and 24 h
      after stressful mock captivity. Cardiovascular (heart rate [HR], systolic blood
      pressure [SBP], diastolic blood pressure [DBP]) and dissociative states were
      measured at all three time points. Psychological impact of mock captivity was
      assessed during recovery. General linear modeling with repeated measures
      evaluated sex differences for each cardiovascular endpoint, and causal steps
      modeling was used to explore interrelationships among sex, cardiovascular
      reactions and psychological impact of mock captivity. Although females had lower
      SBP than males at all three time points, the difference was most pronounced at
      baseline and during stress. Accordingly, females showed greater residual
      elevation in SBP during recovery. Females had lower DBP at all three time points.
      In addition, females reported greater psychological impact of mock captivity than
      males. Exploratory causal steps modeling suggested that stress-induced HR may
      partially mediate the effect of sex on psychological impact of mock captivity. In
      conclusion, this study demonstrated sex-specific cardiovascular stress reactions
      in military personnel, along with greater psychological impact of stress exposure
      in females. This research may elucidate sex differences in PTSD development.

PMID- 24320604
TI  - Base-pairing energies of proton-bound heterodimers of cytosine and modified
      cytosines: implications for the stability of DNA i-motif conformations.
AB  - The DNA i-motif conformation was discovered in (CCG)*(CGG)n trinucleotide
      repeats, which are associated with fragile X syndrome, the most widespread
      inherited cause of mental retardation in humans. The DNA i-motif is a four
      stranded structure whose strands are held together by proton-bound dimers of
      cytosine (C(+)*C). The stronger base-pairing interactions in C(+)*C proton-bound
      dimers as compared to Watson-Crick G*C base pairs are the major forces
      responsible for stabilization of i-motif conformations. Methylation of cytosine
      results in silencing of the FMR1 gene and causes fragile X syndrome. However, the
      influence of methylation or other modifications such as halogenation of cytosine
      on the base-pairing energies (BPEs) in the i-motif remains elusive. To address
      this, proton-bound heterodimers of cytosine and 5-methylcytosine, 5
      fluorocytosine, 5-bromocytosine, and 5-iodocytosine are probed in detail.
      Experimentally, the BPEs of proton-bound heterodimers of cytosine and modified
      cytosines are determined using threshold collision-induced dissociation (TCID)
      techniques. All modifications at the 5-position of cytosine are found to lower
      the BPE and therefore would tend to destabilize DNA i-motif conformations.
      However, the BPEs in these proton-bound heterodimers still significantly exceed
      those of the Watson-Crick G*C and neutral C*C base pairs, suggesting that C(+)*C
      mismatches are still energetically favored such that i-motif conformations are
      preserved. Excellent agreement between TCID measured BPEs and B3LYP calculated
      values is found with the def2-TZVPPD and 6-311+G(2d,2p) basis sets, suggesting
      that calculations at these levels of theory can be employed to provide reliable
      energetic predictions for related systems. 

PMID- 24320605
TI  - Synthetic antimalarial drugs and the triggering of psoriasis - do we need disease
      specific guidelines for the management of patients with psoriasis at risk of
      malaria?
AB  - BACKGROUND: Alpha distinct side effect of the synthetic quinolinic antimalarial
      drugs, still widely used for the treatment and prophylaxis of malaria, is the
      induction of psoriasis in predisposed or susceptible individuals. OBJECTIVE: To
      describe two patients that had induction and exacerbation of psoriasis due to the
      administration of hydroxychloroquine, to adapt pertinent literature on the
      pathophysiology of this side effect, to review psoriasis-triggered cases by
      newer, non-quinolinic antimalarials, and to propose malaria treatment and
      prophylaxis guidelines for psoriatic patients. PATIENTS AND METHODS: Two
      patients, a 40-year-old female with unknown history of psoriasis and a 37-year
      old primigravida with an established history of psoriasis, were treated with
      hydroxychloroquine for a newly diagnosed lichen planopilaris and for an
      exacerbation of psoriatic arthritis, respectively. PubMed was searched (last
      accessed 20 October 2012) employing as search strategy the keywords (psoriasis)
      AND (drug), where "drug" is the name of each of the newer, non-quinolinic
      antimalarials. RESULTS: Psoriasis was controlled in both patients. The
      primigravida gave birth to a healthy child at 39 weeks of gestation. The
      literature review returned no articles that linked the newer antimalarials with
      psoriasis. CONCLUSION: Despite the increased awareness, antimalarials-triggered
      psoriasis is still diagnosed. Fortunately, the current artemisinin-based
      antimalarial treatment can be safely offered to susceptible individuals.
      Additionally, prophylaxis with doxycycline or the combination atovaquone
      proguanil could be a safe suggestion for malaria prophylaxis in psoriatic
      patients.

PMID- 24320606
TI  - Role of arrhythmogenic superior vena cava on atrial fibrillation.
AB  - BACKGROUND: It is well known that superior vena cava (SVC) is one of the
      important non-pulmonary vein (PV) foci of atrial fibrillation (AF). However,
      little is known regarding the role of arrhythmogenic SVC in AF. METHODS AND
      RESULTS: Among 1,425 patients who underwent AF ablation in 2 centers, PV antrum
      isolation was performed in all and SVC isolation was added in 74 (5.2%) patients
      with arrhythmogenic SVC (58 +/- 10 years; 54 males) when the latter was
      identified as an AF source. The arrhythmogenicity was identified at the 1st, 2nd,
      and 3rd procedures in 62 (83.8%), 7 (9.5%), and 5 (6.7%) patients, respectively.
      In 7 (9.5%), 26 (35.1%), and 14 (18.9%) patients, it was identified following
      adenosine injection, isoproterenol infusion, and electrical cardioversion,
      respectively. SVC triggering AF was identified in 58 out of 74 (78.4%) patients.
      In this subset, AF initiated from SVC; however, AF cycle length was longer in SVC
      than in the right atrium once AF persisted, which suggested its role as an
      initiator. In 24 (32.4%) patients following the isolation of SVC, AF terminated
      or converted to atrial flutter and/or confined SVC tachycardia/fibrillation was
      observed, which suggested its role as a perpetuator. Sixty-four (86.5%) of 74
      patients were free from any atrial tachyarrhythmias without antiarrhythmic drugs
      mean 12.1 +/- 9.4 months after the last ablation procedure (mean 1.38
      procedures/patient). CONCLUSIONS: In a subset of patients, SVC plays a role in AF
      not only as an initiator/trigger but also as a driver/perpetuator.

PMID- 24320607
TI  - Testing the link between community structure and function for ectomycorrhizal
      fungi involved in a global tripartite symbiosis.
AB  - Alnus trees associate with ectomycorrhizal (ECM) fungi and nitrogen-fixing
      Frankia bacteria and, although their ECM fungal communities are uncommonly host
      specific and species poor, it is unclear whether the functioning of Alnus ECM
      fungal symbionts differs from that of other ECM hosts. We used exoenzyme root tip
      assays and molecular identification to test whether ECM fungi on Alnus rubra
      differed in their ability to access organic phosphorus (P) and nitrogen (N) when
      compared with ECM fungi on the non-Frankia host Pseudotsuga menziesii. At the
      community level, potential acid phosphatase (AP) activity of ECM fungal root tips
      from A. rubra was significantly higher than that from P. menziesii, whereas
      potential leucine aminopeptidase (LA) activity was significantly lower for A.
      rubra root tips at one of the two sites. At the individual species level, there
      was no clear relationship between ECM fungal relative root tip abundance and
      relative AP or LA enzyme activities on either host. Our results are consistent
      with the hypothesis that ECM fungal communities associated with Alnus trees have
      enhanced organic P acquisition abilities relative to non-Frankia ECM hosts. This
      shift, in combination with the chemical conditions present in Alnus forest soils,
      may drive the atypical structure of Alnus ECM fungal communities. 

PMID- 24320608
TI  - Screening for the presence of patulin in molded fresh produce and evaluation of
      its stability in the production of tomato products.
AB  - A screening for the presence of patulin in molded fresh produce was conducted.
      Patulin was present in 11% of the sweet bell peppers and in 8% of the soft red
      fruits, but not in onions. Patulin was also found in tomatoes, but could not be
      detected in derived tomato products. When the production process of tomato
      concentrates was simulated, none of the evaluated hypotheses could however
      explain a complete degradation of patulin. It was thus concluded that the tomato
      varieties used for further processing are probably less susceptible to
      infestation by patulin-producing molds compared to tomatoes used for the fresh
      market. This was confirmed by screening for patulin throughout the production
      process of tomato concentrate, gazpacho, and salmorejo in three different
      countries; all 191 samples were negative for patulin. Therefore, it can be
      concluded that no health risk can be associated with derived tomato products
      considering this particular mycotoxin. 

PMID- 24320609
TI  - Hysteroscopy and suction evacuation of cesarean scar pregnancies: a case report
      and review.
AB  - Implantation of a pregnancy into the scar of a prior cesarean is an uncommon type
      of ectopic pregnancy. The incidence of cesarean scar pregnancy is thought to be
      one in 1800-2216 pregnancies. The increase in the incidence of cesarean scar
      pregnancy is thought to be a consequence of the increasing rates of cesarean
      delivery. The natural history of cesarean scar pregnancy is unknown. However, if
      such a pregnancy is allowed to continue, uterine scar rupture with hemorrhage and
      possible hysterectomy seem likely. Two early diagnosed cesarean scar pregnancies
      were treated with hysteroscopy and suction curettage removal. One required
      intramuscular methotrexate to resolve a persistent cesarean scar ectopic
      pregnancy. It would seem reasonable that simple suction evacuation would
      frequently leave chorionic villi imbedded within the cesarean scar, as the
      pregnancy is not within the endometrial cavity. 

PMID- 24320610
TI  - Neuroendocrine carcinoma of the breast - a pilot study of a Danish population of
      240 breast cancer patients.
AB  - Neuroendocrine carcinoma of the breast - a very recent diagnosis, which was not
      recognized by WHO until 2003 - has lately been the subject of increasing
      attention. It is defined as a primary breast cancer with morphologic features
      similar to other types of neuroendocrine tumors of the lung and gastrointestinal
      tract combined with positive neuroendocrine immunohistochemical markers. While
      much information has been gathered during the last decade, most studies suffer
      from poor statistics due to a low incidence, and there are still fundamental open
      questions regarding etiology and prognosis. Furthermore, apparent limitations of
      the WHO definition appear to influence diagnosis. Here, we present our own
      results obtained from 13 cases and furthermore review previous reports with
      particular reference to incidence, clinical, histological, and prognostic
      features.

PMID- 24320611
TI  - Physiological expression of the PI3K-activating mutation Pik3ca(H1047R) combines
      with Apc loss to promote development of invasive intestinal adenocarcinomas in
      mice.
AB  - PIK3CA, the gene encoding the p110alpha catalytic subunit of PI3K
      (phosphoinositide 3-kinase), is mutated in approximately 20% of sporadic CRCs
      (colorectal cancers), but the role of these mutations in the pathogenesis of CRC
      remains unclear. In the present study we used a novel mouse model to investigate
      the role of the Pik3caH1047R mutation, the most common PIK3CA mutation in CRC,
      during the development and progression of intestinal cancer. Our results
      demonstrate that Pik3caH1047R, when expressed at physiological levels, is
      insufficient to initiate intestinal tumorigenesis; however, in the context of Apc
      (adenomatous polyposis coli) loss, which is observed in 80% of CRCs and by itself
      results in benign intestinal adenomas, the Pik3caH1047R mutation promotes the
      development of highly aggressive and invasive adenocarcinomas in both the small
      and large intestines. The results of the present study show that an activating
      Pik3ca mutation can act in tandem with Apc loss to drive the progression of
      gastrointestinal cancer and thus this disease may be susceptible to therapeutic
      targeting using PI3K pathway inhibitors. 

PMID- 24320612
TI  - Video-assisted unilateral cricoarytenoid laryngoplasty in 14 dogs with bilateral
      idiopathic laryngeal paralysis.
AB  - BACKGROUND: Unilateral cricoarytenoid laryngoplasty is commonly performed for
      treatment of idiopathic laryngeal paralysis in dogs. Determination of the
      appropriate tension applied to the suture can be difficult, particularly for the
      novice surgeon. OBJECTIVE: To describe a technique for video-assisted unilateral
      cricoarytenoid laryngoplasty (VAUCAL) and to report short-term outcome in dogs
      undergoing VAUCAL. ANIMALS AND METHODS: Dogs (n = 14) with bilateral idiopathic
      laryngeal paralysis undergoing VAUCAL between August 2011 and May 2013 were
      evaluated. A cricoarytenoid suture was tensioned under video observation of the
      rima glottidis using a 5-mm rigid endoscope. Real-time visualization of arytenoid
      abduction during suture tensioning, and final arytenoid position were assessed.
      Requirement for additional intravenous anesthestic, intra- and post-operative
      complications and short-term outcomes were documented. RESULTS: Adequate, real
      time visualization of the larynx during tensioning of the cricoarytenoid suture
      was accomplished in 13/14 dogs. Additional intravenous anesthesia was required in
      5/14 dogs to facilitate reintubation. Final arytenoid position was considered
      inadequate in two dogs on post-operative trans-oral laryngeal examination.
      Recurrence of clinical signs occurred in one dog three months following initial
      surgery. Owner outcome was deemed good (n = 8) or excellent (n = 6). CONCLUSIONS:
      VAUCAL is a feasible technique to permit direct real-time visualization of the
      larynx during tensioning of the cricoarytenoid suture, and enables assessment of
      final arytenoid position intra-operatively by the operating surgeon. CLINICAL
      IMPORTANCE: VAUCAL allows the operating surgeon to assess arytenoid abduction
      intra-operatively, at the time of knot placement. This technique may be
      particularly useful for the novice surgeon or surgeon in training.

PMID- 24320613
TI  - Perfluorooctanoate exposure in a highly exposed community and parent and teacher
      reports of behaviour in 6-12-year-old children.
AB  - BACKGROUND: In toxicology studies, perfluorinated compounds affect fetal growth,
      development, viability, and postnatal growth. There are limited epidemiologic
      studies on child development. METHODS: We recruited and evaluated 321 children
      who participated in the C8 Health Project, a 2005-06 survey in a mid-Ohio Valley
      community highly exposed to perfluorooctanoate (PFOA) through contaminated
      drinking water. We examined associations between measured childhood PFOA serum
      concentration and mother and teacher reports of executive function (Behaviour
      Rating Inventory of Executive Function), attention deficit hyperactivity disorder
      (ADHD)-like behaviour (Conner's ADHD Diagnostic and Statistical Manual of Mental
      Disorders IV Scales), and behavioural problems (Behaviour Assessment System for
      Children) assessed 3 to 4 years later at ages 6-12 years. RESULTS: Overall,
      neither reports from mothers nor teachers provided clear associations between
      exposure and child behaviour. Mother reports, however, did suggest favourable
      associations between exposure and behaviour among boys and adverse associations
      among girls. On the composite scale from the Behaviour Rating Inventory of
      Executive Function (n = 318), PFOA exposure had a favourable association among
      boys (highest vs. lowest quartile beta = -6.39; 95% confidence interval [CI] 
      11.43, -1.35) and an adverse association among girls (highest vs. lowest quartile
      beta = 4.42; 95% CI -0.03, 8.87; interaction P = 0.01). Teacher reports (n = 189)
      replicated some, but not all of the sex interactions observed in mothers'
      reports. CONCLUSIONS: Aggregate results did not suggest adverse effects of PFOA
      on behaviour, but sex-specific results raise the possibility of differing
      patterns by sex. Results are not consistent between mothers' and teachers'
      reports. Effect modification by sex may warrant further investigation.

PMID- 24320614
TI  - Soluble receptor for advanced glycation end products independently predicts
      cardiometabolic syndrome in Latino youth.
AB  - OBJECTIVE: The soluble receptor for advanced glycation end products (sRAGE) has
      anti-atherogenic properties in adults, however, little is known about the
      relationship between sRAGE and cardiometabolic disease risk in pediatric
      populations. Therefore, the purpose of this investigation is to examine the
      relationship between sRAGE and cardiometabolic risk factors in Latino youth.
      RESEARCH DESIGN AND METHODS: Data from 133 Latino youth (58% female; age 16.3 +/-
      2.8 yr) enrolled in the Arizona Insulin Resistance Registry were analyzed.
      Cardiometabolic syndrome was determined using a continuous risk score normalized
      to the population. Components included waist circumference, high-density
      lipoprotein cholesterol (HDL-c), triglycerides, mean arterial pressure (MAP), and
      homeostatic assessment of insulin resistance (HOMA-IR). sRAGE levels were
      determined from fasting serum using an enzyme-linked immunosorbent assay.
      RESULTS: In univariate analysis, sRAGE was inversely associated with waist
      circumference (r = -0.22, p = 0.01), MAP (r = -0.15, p = 0.09), and HOMA-IR (r = 
      0.29, p < 0.01) and positively associated with HDL-c (r = 0.19, p < 0.05). In
      multiple regression analysis with age, sex, and BMI, sRAGE remained an
      independent predictor of cardiometabolic syndrome risk score (R(2) = 0.55, p <
      0.001). CONCLUSIONS: These data suggest that sRAGE may be an early independent
      biomarker of cardiometabolic disease risk in youth. Prospective studies are
      needed to establish the predictive utility of sRAGE for long-term disease
      outcomes.

PMID- 24320615
TI  - Pudendal nerve stimulation and block by a wireless-controlled implantable
      stimulator in cats.
AB  - OBJECTIVE: The study aims to determine the functionality of a wireless-controlled
      implantable stimulator designed for stimulation and block of the pudendal nerve.
      MATERIALS AND METHODS: In five cats under alpha-chloralose anesthesia, the
      stimulator was implanted underneath the skin on the left side in the lower back
      along the sacral spine. Two tripolar cuff electrodes were implanted bilaterally
      on the pudendal nerves in addition to one bipolar cuff electrode that was
      implanted on the left side central to the tripolar cuff electrode. The stimulator
      provided high-frequency (5-20 kHz) biphasic stimulation waveforms to the two
      tripolar electrodes and low-frequency (1-100 Hz) rectangular pulses to the
      bipolar electrode. Bladder and urethral pressures were measured to determine the
      effects of pudendal nerve stimulation (PNS) or block. RESULTS: The maximal (70
      100 cmH2O) urethral pressure generated by 20-Hz PNS applied via the bipolar
      electrode was completely eliminated by the pudendal nerve block induced by the
      high-frequency stimulation (6-15 kHz, 6-10 V) applied via the two tripolar
      electrodes. In a partially filled bladder, 20-30 Hz PNS (2-8 V, 0.2 ms) but not 5
      Hz stimulation applied via the bipolar electrode elicited a large sustained
      bladder contraction (45.9 +/- 13.4 to 52.0 +/- 22 cmH2O). During cystometry, the
      5 Hz PNS significantly (p < 0.05) increased bladder capacity to 176.5 +/- 27.1%
      of control capacity. CONCLUSIONS: The wireless-controlled implantable stimulator
      successfully generated the required waveforms for stimulation and block of
      pudendal nerve, which will be useful for restoring bladder functions after spinal
      cord injury.

PMID- 24320617
TI  - Complete mitochondrial DNA genome of the medicinal mushroom Cordyceps militaris
      (Ascomycota, Cordycipitaceae).
AB  - In this study, the complete mitochondrial genome of the medicinal mushroom
      Cordyceps militaris (Ascomycota, Cordycipitaceae) was sequenced. This
      mitochondrial genome is 33,277 bp in length and consisted of 14 protein-coding
      genes, 2 ribosomal RNA subunits and 27 transfer RNAs. The overall nucleotide
      composition of is 36.98% A, 26.23% T, 15.21% G and 11.59% C, with an AT bias of
      73.21%. The mtDNA of C. militaris contains a total of eight group-I introns of
      which total size is 11,052 bp in length and four of them are in the rnl gene. The
      mitochondrial genome of C. militaris presented here provides the complete genome
      information of C. militaris.

PMID- 24320618
TI  - Lung and serum teicoplanin concentration after aerosol and intravenous
      administration in a rat model.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) caused by methicillin-resistant
      Staphylococcus aureus is a major cause of mortality in mechanically ventilated
      patients. Nebulization of teicoplanin is an alternative way of administration
      that may provide higher lung tissue concentrations than intravenous (IV)
      delivery. The aim of this study was to compare the administration of teicoplanin
      via aerosol with the IV route by measuring the lung and the serum teicoplanin
      concentrations in a rat model. METHODS: Eighty healthy male Sprague-Dawley rats
      were anesthetized and received a single dose of teicoplanin by the IV or aerosol
      route. After sacrifice, lung and blood samples were collected and teicoplanin
      concentrations were measured with fluorescence polarization. A noncompartmental
      approach was used. The area under the concentration curve/minimal inhibition
      concentration ratio (AUC/MIC), AUC, absorbed fraction, mean residence time (MRT),
      and mean absorption time (MAT) of teicoplanin were calculated. RESULTS: Mean+/-SD
      lung tissue concentrations of teicoplanin in the aerosol group were significantly
      higher than those in the IV group (p<0.0001). The mean lung tissue concentration
      achieved at 15 min was 1.94+/-1.33 mg/g in the aerosol group and 0.04+/-0.01 mg/g
      in the IV group. The mean AUClung was 67.4 mg hr(-1)g(-1) after aerosol and 0.8
      mg hr(-1)g(-1) after the IV route. In the aerosol group, AUCserum/MIC ratio was
      605/2, and in the IV route, AUCserum/MIC ratio was 682/2. MAT was longer after
      aerosol than after the IV route (0.91 hr versus 0.06 hr), and MRT was longer
      after aerosol than after IV bolus administration (6.52 hr versus 5.61 hr).
      CONCLUSION: Teicoplanin concentrations in the lung tissue of the rat model were
      significantly higher by the aerosol route than by the IV route. The AUClung after
      nebulization was 84 times higher than delivery by the IV route, and the
      AUClung/MIC ratio after nebulization met the recommended target to eradicate
      Staphylococcus aureus. Administration of teicoplanin by the aerosol route could
      represent one of the new therapeutic weapons of the treatment of the VAP.

PMID- 24320616
TI  - Beyond modules and hubs: the potential of gene coexpression networks for
      investigating molecular mechanisms of complex brain disorders.
AB  - In a research environment dominated by reductionist approaches to brain disease
      mechanisms, gene network analysis provides a complementary framework in which to
      tackle the complex dysregulations that occur in neuropsychiatric and other
      neurological disorders. Gene-gene expression correlations are a common source of
      molecular networks because they can be extracted from high-dimensional disease
      data and encapsulate the activity of multiple regulatory systems. However, the
      analysis of gene coexpression patterns is often treated as a mechanistic black
      box, in which looming 'hub genes' direct cellular networks, and where other
      features are obscured. By examining the biophysical bases of coexpression and
      gene regulatory changes that occur in disease, recent studies suggest it is
      possible to use coexpression networks as a multi-omic screening procedure to
      generate novel hypotheses for disease mechanisms. Because technical processing
      steps can affect the outcome and interpretation of coexpression networks, we
      examine the assumptions and alternatives to common patterns of coexpression
      analysis and discuss additional topics such as acceptable datasets for
      coexpression analysis, the robust identification of modules, disease-related
      prioritization of genes and molecular systems and network meta-analysis. To
      accelerate coexpression research beyond modules and hubs, we highlight some
      emerging directions for coexpression network research that are especially
      relevant to complex brain disease, including the centrality-lethality
      relationship, integration with machine learning approaches and network
      pharmacology. 

PMID- 24320619
TI  - Defect closure in the paranasal region: an enduring challenge.
AB  - BACKGROUND: The paranasal region constitutes a demanding issue for the
      reconstructive surgeon. Its complex anatomy, with concavity in close contact with
      convexity, and a high density of functional and aesthetically important facial
      components demands specific concern. Due to such complexity, numerous procedures
      for the reconstruction of paranasal defects have been published, including skin
      grafts and flaps in random pattern or axial style from the glabella, upper lid,
      nasal root, or cheek. OBJECTIVES: In this review, we recall classical
      reconstructive procedures and compare them with innovative procedures that could
      possibly gain importance in the following years. METHODS: We contrast the pros
      and cons concerning donor site morbidity, surgical elaborateness, and functional
      and aesthetic outcome, and substantiate our findings with photographic results
      from our own patient material. RESULTS AND CONCLUSION: The reconstruction of
      paranasal defects remains a challenge; nevertheless, the growing toolbox of
      reconstructive instruments facilitates a perfect reconstructive result.

PMID- 24320620
TI  - SIS8, a putative mitogen-activated protein kinase kinase kinase, regulates sugar
      resistant seedling development in Arabidopsis.
AB  - Sugar signaling pathways have been evolutionarily conserved among eukaryotes and
      are postulated to help regulate plant growth, development and responses to
      environmental cues. Forward genetic screens have identified sugar signaling or
      response mutants. Here we report the identification and characterization of
      Arabidopsis thaliana sugar insensitive8 (sis8) mutants, which display a sugar
      resistant seedling development phenotype. Unlike many other sugar insensitive
      mutants, sis8 mutants exhibit wild-type responses to the inhibitory effects of
      abscisic acid and paclobutrazol (an inhibitor of gibberellin biosynthesis) on
      seed germination. Positional cloning of the SIS8 gene revealed that it encodes a
      putative mitogen-activated protein kinase kinase kinase (MAPKKK; At1g73660).
      SIS8mRNA is expressed ubiquitously among Arabidopsis organs. A UDP
      glucosyltransferase, UGT72E1 (At3g50740), was identified as an interacting
      partner of SIS8 based on a yeast two-hybrid screen and in planta bimolecular
      fluorescence complementation. Both SIS8-yellow fluorescent protein (YFP) and
      UGT72E1-YFP fusion proteins localize to the nucleus when transiently expressed in
      tobacco leaf cells. T-DNA insertions in At3g50740 cause a sugar-insensitive
      phenotype. These results indicate that SIS8, a putative MAPKKK, is a regulator of
      sugar response in Arabidopsis and interacts with a UDP-glucosyltransferase in the
      nucleus. 

PMID- 24320621
TI  - Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2
      diabetes: a meta-analysis of randomized clinical trials.
AB  - AIMS: Sodium glucose co-transport-2 (SGLT-2) inhibitors, a new class of glucose
      lowering agents, reduce tubular glucose reabsorption, producing a reduction of
      blood glucose without stimulating insulin release. The aim of the present meta
      analysis is the assessment of the overall efficacy and safety profile of these
      drugs. METHODS: A meta-analysis was performed including all trials with a
      duration of at least 12 weeks, comparing a SGLT-2 inhibitor with a non-SGLT-2
      inhibitor agent in type 2 diabetes. The principal outcome of this analysis was
      the effect of SGLT-2 inhibitors on HbA1c at 12, 24 and 52 weeks. Hypoglycaemia,
      genital and urinary infections were retrieved and combined to calculate Mantel
      Haenszel odds ratio (MH-OR). Furthermore, data on body mass index (BMI), endpoint
      fasting plasma glucose, systolic and diastolic blood pressure, creatinine,
      hematocrit and lipid profile were collected. RESULTS: Among placebo-controlled
      trials, HbA1c reduction at 12, 24 and 52 weeks was 0.5 [0.4; 0.6], 0.6 [0.6; 0.5]
      and 0.6 [0.7; 0.5]%. In placebo-controlled studies, 24-week reduction of HbA1c
      with SGLT-2 inhibitors was greater in trials enrolling patients with a lower mean
      age and duration of diabetes, and a higher baseline BMI, HbA1c and fasting
      glucose. In placebo-controlled trials, SGLT-2 inhibitors determined a weight loss
      during the first 24 weeks, which was maintained up to 52 weeks. CONCLUSIONS: SGLT
      2 inhibitors are effective in the treatment of type 2 diabetes, providing
      additional benefits, such as weight loss, reduction of blood pressure and
      increase in high-density lipoprotein (HDL)-cholesterol. Apart from genital and
      urinary infections, rather frequent but usually mild, SGLT-2 inhibitors appear to
      be well tolerated.

PMID- 24320623
TI  - Loop-mediated isothermal amplification assay for detection of Histomonas
      meleagridis infection in chickens targeting the 18S rRNA sequences.
AB  - Histomonas meleagridis is the causative agent of histomonosis, a disease of
      gallinaceous fowl characterized by necrotic typhlitis, hepatitis, and high
      mortality. To develop a rapid and sensitive method for specific detection of H.
      meleagridis, an assay based on loop-mediated isothermal amplification (LAMP)
      targeting the 18S rRNA gene was established. The detection limit of the LAMP
      assay was 10 copies for standard plasmids containing an 18S rRNA gene fragment,
      which was superior to that of a classical PCR method. Specificity tests revealed
      that there was no cross-reaction with other protozoa such as Trichomonas
      gallinae, Blastocytis sp, Tetratrichomonas gallinarum, Plasmodium gallinaceum,
      Toxoplasma gondii, Eimeria tenella, Leucocytozoon caulleryi and Leucocytozoon
      sabrazesi. The assay was evaluated for its diagnostic utility using liver and
      caeca samples collected from suspected field cases, the detection rate was 100
      and 97.92%, respectively. These results indicate that the LAMP assay may be a
      useful tool for rapid detection and identification of H. meleagridis in poultry. 

PMID- 24320622
TI  - Comparative transcriptional profiling analysis of olive ripe-fruit pericarp and
      abscission zone tissues shows expression differences and distinct patterns of
      transcriptional regulation.
AB  - BACKGROUND: In fleshy fruit, abscission of fully ripe fruit is a process
      intimately linked to the ripening process. In many fruit-tree species, such as
      olive (Olea europaea L. cv. Picual), there is a coupling of the full ripening and
      the activation of the abscission-zone (AZ). Although fully ripe fruit have marked
      physiological differences with respect to their AZs, dissimilarities in gene
      expression have not been thoroughly investigated. The present study examines the
      transcriptome of olive fruit and their AZ tissues at the last stage of ripening,
      monitored using mRNA-Seq. RESULTS: Roche-454 massive parallel pyrosequencing
      enabled us to generate 397,457 high-quality EST sequences, among which 199,075
      were from ripe-fruit pericarp and 198,382 from AZ tissues. We assembled these
      sequences into 19,062 contigs, grouped as 17,048 isotigs. Using the read amounts
      for each annotated isotig (from a total of 15,671), we identified 7,756
      transcripts. A comparative analysis of the transcription profiles conducted in
      ripe-fruit pericarp and AZ evidenced that 4,391 genes were differentially
      expressed genes (DEGs) in fruit and AZ. Functional categorization of the DEGs
      revealed that AZ tissue has an apparently higher response to external stimuli
      than does that of ripe fruit, revealing a higher expression of auxin-signaling
      genes, as well as lignin catabolic and biosynthetic pathway, aromatic amino acid
      biosynthetic pathway, isoprenoid biosynthetic pathway, protein amino acid
      dephosphorylation, amino acid transport, and photosynthesis. By contrast, fruit
      enriched transcripts are involved in ATP synthesis coupled proton transport,
      glycolysis, and cell-wall organization. Furthermore, over 150 transcripts
      encoding putative transcription-factors (TFs) were identified (37 fruit TFs and
      113 AZ TFs), of which we randomly selected eight genes and we confirmed their
      expression patterns using quantitative RT-PCR. CONCLUSION: We generated a set of
      EST sequences from olive fruit at full ripening, and DEGs between two different
      olive tissues, ripe fruit and their AZ, were also identified. Regarding the cross
      talk between fruit and AZ, using qRT-PCR, we confirmed a set of TF genes that
      were differentially expressed, revealing profiles of expression that have not
      previously been reported, this offering a promising beginning for studies on the
      different transcription regulation in such tissues.

PMID- 24320624
TI  - Mechanisms of ultrafast excited-state deactivation in adenosine.
AB  - Recently, resonant two-photon ionization experiments on isolated adenine and
      adenosine suggested that adenosine exhibits a significantly shorter excited-state
      lifetime than adenine, which indicates the existence of an efficient excited
      state deactivation mechanism in adenosine that is not existent in adenine. We
      report on ab initio investigations on a syn and an anti conformer of adenosine
      exhibiting an intramolecular O-H...N3 hydrogen bond. For both conformers, we have
      identified the existence of a barrierless excited-state deactivation mechanism
      that involves the forward-backward transfer of a proton along the intramolecular
      hydrogen bond and ultrafast radiationless deactivation through conical
      intersections. The S1/S0 conical intersection associated with the proton-transfer
      process is lower in energy than the known S1/S0 conical intersections associated
      with the excited-state deactivation processes inherent to the adenine moiety.
      These results support the conjecture that the photochemistry of hydrogen bonds
      plays a decisive role for the photostability of the molecular building blocks of
      RNA and DNA, which have been selected at the earliest stages of the chemical
      evolution of life. 

PMID- 24320625
TI  - A comparative study of nano-SiO2 and nano-TiO2 fillers on proton conductivity and
      dielectric response of a silicotungstic acid-H3PO4-poly(vinyl alcohol) polymer
      electrolyte.
AB  - The effects of nano-SiO2 and nano-TiO2 fillers on a thin film silicotungstic acid
      (SiWA)-H3PO4-poly(vinyl alcohol) (PVA) proton conducting polymer electrolyte were
      studied and compared with respect to their proton conductivity, environmental
      stability, and dielectric properties, across a temperature range from 243 to 323
      K. Three major effects of these fillers have been identified: (a) barrier effect;
      (b) intrinsic dielectric constant effect; and (c) water retention effect.
      Dielectric analyses were used to differentiate these effects on polymer
      electrolyte-enabled capacitors. Capacitor performance was correlated to
      electrolyte properties through dielectric constant and dielectric loss spectra.
      Using a single-ion approach, proton density and proton mobility of each polymer
      electrolyte were derived as a function of temperature. The results allow us to
      deconvolute the different contributions to proton conductivity in SiWA-H3PO4-PVA
      based electrolytes, especially in terms of the effects of fillers on the dynamic
      equilibrium of free protons and protonated water in the electrolytes. 

PMID- 24320626
TI  - Novel presentation of lepromatous leprosy in an erythema gyratum repens-like
      pattern.
AB  - OBJECTIVES: Leprosy can have diverse cutaneous and occasionally perplexing
      presentations. We report an unusual case of lepromatous leprosy (LL) with annular
      lesions resembling erythema gyratum repens. REPORT: A 55-year-old man presented
      with a symmetrical, hypopigmented, and erythematous rash of bizarre appearance
      over the lateral aspect of the upper arm, and anterior and posterior aspects of
      the trunk of two months' duration. He gave a history of self-resolving episodes
      of bilateral pedal edema, and numbness and pricking sensations in both the hands
      and feet, which had occurred intermittently over the previous six years. An ulcer
      measuring 2 cm in size was present over the adjacent surface of the right first
      and second toes. The bilateral ulnar and radial cutaneous nerves were
      symmetrically thickened. RESULTS: Slit-skin smears revealed numerous acid-fast
      bacilli. Skin biopsy from the trunk showed collections of histiocytes,
      lymphocytes, and plasma cells in the dermis and around the blood vessels. The
      patient was diagnosed with LL and started on multibacillary multi-drug therapy.
      CONCLUSIONS: Lepromatous leprosy can have varied clinical manifestations and is
      often a great imitator. However, the skin smear positivity, even in normal skin,
      symmetrical cutaneous and peripheral nerve involvement, and histopathology in the
      present patient were indicative of LL. This report highlights a rare presentation
      of leprosy. Clinicians should be aware of these rare manifestations as
      lepromatous cases still occur in certain regions.

PMID- 24320627
TI  - Value of maternal procalcitonin levels for predicting subclinical intra-amniotic
      infection in preterm premature rupture of membranes.
AB  - AIM: To determine whether procalcitonin (ProCT) levels can be used to predict
      subclinical intra-amniotic infection by comparing maternal plasma levels in
      preterm premature rupture of membranes (PPROM) and premature rupture of membranes
      (PROM) at term with the levels in healthy pregnant women. METHODS: The mean
      plasma ProCT levels of 32 patients with PPROM, 35 patients with PROM at term, 24
      healthy women at preterm gestation and 30 healthy women at term were compared. In
      the PPROM group, the presence or absence of histological chorioamnionitis and
      neonatal infection were used as a reference to analyze ProCT levels. RESULTS: The
      mean ProCT level of patients in the PPROM group was significantly higher than
      those in the PROM group and healthy controls. Patients in the PPROM group
      diagnosed with histological chorioamnionitis had significantly higher ProCT
      levels than those of the remaining patients. At a cut-off of 0.054 ng/mL, the
      sensitivity and specificity of ProCT to predict histological chorioamnionitis
      were 92.3% and 68.4%, respectively. CONCLUSION: ProCT levels were significantly
      higher in patients with PPROM, and facilitate identification of those who require
      expectant management.

PMID- 24320628
TI  - Microporous organic network hollow spheres: useful templates for nanoparticulate
      Co(3)O(4) hollow oxidation catalysts.
AB  - Hollow microporous organic networks (H-MONs) were prepared by a template method
      using silica spheres. The shell thickness was delicately controlled by changing
      the synthetic conditions. The H-MONs were used as a template for the synthesis of
      nanoparticulate Co3O4 hollows which showed excellent catalytic performance in
      H2O2 oxidation. 

PMID- 24320629
TI  - Efficient photosensitization by a chlorin-polyoxometalate supramolecular complex.
AB  - The 4:1 supramolecular complexed ionic salt between pyridinium chlorin and
      polyanionic [alpha-SiMo12O40](4-) exhibits significantly enhanced photodynamic
      activity against A549 cell lines because of increased singlet oxygen
      photogeneration through high cellular penetration and localization of the chlorin
      molecules on the ionic salt into the cancer cell. Confocal laser scanning
      microscopy images clearly represent a higher uptake and photodynamic effect of
      this supramolecular complex corresponding to the lower IC50 value compared to the
      free chlorin. 

PMID- 24320648
TI  - Race talk: the psychology of racial dialogues.
AB  - Constructive dialogues on race have been proposed as a means to heal racial and
      ethnic divides, reduce prejudice and misinformation, increase racial literacy,
      and foster improved race relations. Studies on the psychology of racial dialogues
      indicate social and academic norms that dictate against race talk between White
      Americans and persons of color: (a) the politeness protocol, (b) the academic
      protocol, and (c) the color-blind protocol. These protocols discourage race talk
      and allow society to enter into a conspiracy of silence regarding the detrimental
      impact oppression plays on persons of color. Facilitating difficult dialogues on
      race requires educators to recognize what makes such discussions difficult. For
      people of color, engaging in race talk exposes them to microaggressions that
      invalidate and assail their racial/ethnic identities. For Whites, honest
      discussions are impeded by fears of appearing racist, of realizing their racism,
      of acknowledging White privilege, and of taking responsibility to combat racism.

PMID- 24320634
TI  - It's all connected: Pathways in visual object recognition and early noun
      learning.
AB  - A developmental pathway may be defined as the route, or chain of events, through
      which a new structure or function forms. For many human behaviors, including
      object name learning and visual object recognition, these pathways are often
      complex and multicausal and include unexpected dependencies. This article
      presents three principles of development that suggest the value of a
      developmental psychology that explicitly seeks to trace these pathways and uses
      empirical evidence on developmental dependencies among motor development, action
      on objects, visual object recognition, and object name learning in 12- to 24
      month-old infants to make the case. The article concludes with a consideration of
      the theoretical implications of this approach. (PsycINFO Database Record (c) 2013
      APA, all rights reserved). 

PMID- 24320650
TI  - Faith to move mountains: religious coping, spirituality, and interpersonal trauma
      recovery.
AB  - Interpersonal trauma is pervasive globally and may result in long-term
      consequences physically, cognitively, behaviorally, socially, and spiritually
      (Bryant-Davis, 2005b). One of the protective factors that have emerged in the
      literature is religious coping. Religious coping, spirituality, and faith-based
      approaches to trauma recovery include endorsement of beliefs, engagement in
      behaviors, and access to support from faith communities. Compared with negative
      religious coping, spirituality and positive religious coping have been associated
      with decreased psychological distress, a finding established with survivors of
      child abuse, sexual violence, intimate partner violence, community violence, and
      war. This article focuses on spiritual and religious coping among survivors of
      child abuse, sexual violence, and war; however, research demonstrates increased
      use of positive religious coping among some survivors with higher rates of
      posttraumatic stress disorder. Much of the scholarship in this area includes
      qualitative studies with populations who face increased vulnerability to
      interpersonal trauma. Research in this area covers the life span from childhood
      to later adulthood and encompasses both domestic and international studies. The
      implications of research findings are explored, and future research needs are
      described. This line of research supports the American Psychological Association
      (2010) ethical standards that note the recognition of spiritual and religious
      faith traditions as important aspects of the provision of ethical treatment.
      Researchers, clinicians, and advocates for trauma survivors are encouraged to
      attend to the faith traditions and beliefs of persons confronting the potential
      devastation of traumatic events.

PMID- 24320653
TI  - Echoes of Bedford: a 20-year social psychology memoir on participatory action
      research hatched behind bars.
AB  - Responding to Martin Luther King Jr.'s 1968 address at the American Psychological
      Association calling for a psychology that would educate Whites about racial
      injustice, this article challenges the widening epistemological gap between those
      who suffer from inequality and those who conduct social policy research on
      inequality. In this 20-year memoir on the echoes of a single piece of
      participatory policy research, Changing Minds: The Impact of College in a Maximum
      Security Prison (Fine et al., 2001), readers are invited to explore how deep
      critical participation by a collaborative team of university and prisoner
      researchers has facilitated theoretical and methodological complexity, enhanced
      contextual and construct validity, thickened commitments to ethics and action,
      and fueled the political sustainability and generalizability of the findings over
      time and space.

PMID- 24320656
TI  - Quality education in professional psychology: flowers blooming, Flexner, and the
      future.
AB  - The educational system in professional psychology is reviewed, including how it
      utilizes its mission and core values to ensure quality-based educational
      experiences that graduate a quality "product" who ultimately provides quality
      health care services for consumers of psychological care. Education and training
      in, and the practice of, professional psychology must adopt and adapt to changes
      in accountability and quality expectations in the evolving health care system
      brought about by the implementation of the Patient Protection and Affordable Care
      Act. Definitions of "psychologist" and "specialist" are discussed, along with a
      rationale for a clearly articulated educational core that operationalizes
      learning objectives needed to be a competent, successful psychologist.
      Implications for quality assurance, including questions of educational outcomes
      and their impact on clinical outcomes of health care services, are related to the
      education and training sequence. Competency-based education, "pre-psych"
      requirements, evidenced-based care, specialization, and interprofessionalism,
      each a key component of a successful future for professional psychology, are also
      discussed.

PMID- 24320663
TI  - The maintenance of behavioral change: the case for long-term follow-ups.
AB  - This article discusses response maintenance, the durability of behavior change
      after therapy, treatment, or training ends. Response maintenance is one of the
      three forms of generalized behavior change, with the others being
      setting/situation generalization and response generalization. Long-term
      maintenance of treatment effects is an important issue after behavior change has
      taken place and is the goal of most programs. Areas discussed include factors
      affecting the study of maintenance, techniques for programming it, and analyzing
      and evaluating strategies for promoting it. This article presents a number of
      long-term follow-ups of programs designed to treat the addictive behaviors of
      typical adults (Foxx, 1982; Foxx, Brown, & Katz, 1981) and to teach social skills
      (Foxx & Faw, 1992) and language (Foxx & Faw, 1990) to individuals with
      intellectual disabilities and autism as well as to decrease their severe
      maladaptive behaviors (Foxx, 1990; Foxx & Livesay, 1984). In the process, various
      factors that appeared to contribute to long-term maintenance are identified. The
      article concludes with some recommendations regarding the study of maintenance.

PMID- 24320672
TI  - Contributions to the study and promotion of resilience in socially vulnerable
      children.
AB  - Young children are particularly susceptible to the adverse effects of social
      vulnerability. Resilient children are those who resist adversity, manage to cope
      with uncertainty, and are able to recover successfully from trauma. Becoming
      familiar with the characteristics of naturally resilient children allows
      preventive intervention policies to be designed. Given that resilience
      interventions are an integrative process, it is necessary to work in different
      environments: family, school, and neighborhood. Interventions addressing the
      resources of socially vulnerable children appear to have quite an important role
      when children are faced with threats. But for the intervention's effects on the
      child's resources to be maintained or improved, the intervention needs to be
      intensive and continued over time. The child's age when the intervention begins
      is also an important factor. It has been determined that the earlier the
      intervention begins, the better the obtained results will be. (PsycINFO Database
      Record (c) 2013 APA, all rights reserved). 

PMID- 24320674
TI  - Contributions of internationalization to psychology: toward a global and
      inclusive discipline.
AB  - In this article I define and describe the current state of internationalization
      in psychology. Internationalization refers here to the approach in which existing
      or new psychological theories, methods, procedures, or data across cultures are
      synthesized so as to create a more culture-informed, inclusive, and globally
      applicable science and profession. This approach is essential to advance
      psychology beyond its Euro-American context of development and to achieve a more
      global applicability of its theories and professional procedures.
      Internationalization already has led to a better integration of cultural aspects
      in various psychological theories, to more insight into how to deal with
      methodological aspects of intact group comparisons (such as bias and
      equivalence), and to the development of guidelines in areas such as test
      development, test adaptations, ethics codes, and Internet testing. I review
      systemic and scientific climate factors in psychology that thwart the progress of
      internationalization, and conclude by suggesting methods of enhancing
      internationalization, which is essential for developing a truly universal
      psychology.

PMID- 24320677
TI  - Participatory and action research as a transformative praxis: responding to
      humanitarian crises from the margins.
AB  - This article reports on a small set of community-based participatory projects
      designed collaboratively by and for survivors directly affected by armed conflict
      in Guatemala and some of their family members in the North (i.e., in New Orleans,
      Louisiana, and New England). Local protagonists deeply scarred by war and gross
      violations of human rights drew on indigenous beliefs and practices, creativity,
      visual performance arts, and participatory and action research strategies to
      develop and perform collaborative community-based actions. These initiatives
      constitute a people's psychosocial praxis. Through their individual and
      collective narratives and actions, Mayan and African American women and Latinas
      perform a psychology from the "two-thirds world," one that draws on postcolonial
      theory and methodology to retheorize trauma and resilience. These voices,
      creative representations, and actions of women from the Global South transform
      earlier, partial efforts to decenter EuroAmerican epistemologies underlying
      dominant models of trauma that reduce complex collective phenomena to individual
      pathology, refer to continuous trauma as past, are ahistorical, and universalize
      culturally particular realities.

PMID- 24320678
TI  - Study of mutation and misfolding of Cu-Zn SOD1 protein.
AB  - The main objective of this work is to determine the mechanism for misfolding and
      aggregation as a result of mutations in Cu-Zn superoxide dismutase1. The quantum
      mechanical approach is beneficial for investigating the early stages of mutation,
      misfolding, and loss of protection of the native structures involved in the neuro
      degeneration disease Amyotrophic Lateral Sclerosis. All the structures were
      optimized using density functional theory (B3LYP) with 6-31G* and LANL2DZ basis
      sets. The binding energies of the metal ions with their associated residues in
      the active site loop and metal binding loop have been investigated for native and
      metal-bound mutated structures. The metal ion affinity (MIA) was computed for all
      the structures. The binding energy and MIA in gas phase reveal the nature of
      interaction of active site residues with the metal cations. The electronic effect
      prevailing between the side chains of the residues in the active site governing
      the intermolecular interactions is given by the polarizability studies. The role
      of the bridging residue His 63 in the active site of the protein in the native
      and metal-bound mutated structures have been studied using ONIOM method to reveal
      the changes that takes place in the structural parameters during mutation. The
      molecular dynamics simulation is used to explore different dynamic properties of
      active site in native and metal-bound mutated structures. The structural
      information provided by the molecular dynamics simulation illustrates the
      structural consequences in the mutated structures. 

PMID- 24320679
TI  - Intravitreal injections: a review of the evidence for best practice: response.

PMID- 24320680
TI  - Assessment of water droplet evaporation mechanisms on hydrophobic and
      superhydrophobic substrates.
AB  - Evaporation rates are predicted and important transport mechanisms identified for
      evaporation of water droplets on hydrophobic (contact angle ~110 degrees ) and
      superhydrophobic (contact angle ~160 degrees ) substrates. Analytical models for
      droplet evaporation in the literature are usually simplified to include only
      vapor diffusion in the gas domain, and the system is assumed to be isothermal. In
      the comprehensive model developed in this study, evaporative cooling of the
      interface is accounted for, and vapor concentration is coupled to local
      temperature at the interface. Conjugate heat and mass transfer are solved in the
      solid substrate, liquid droplet, and surrounding gas. Buoyancy-driven convective
      flows in the droplet and vapor domains are also simulated. The influences of
      evaporative cooling and convection on the evaporation characteristics are
      determined quantitatively. The liquid-vapor interface temperature drop induced by
      evaporative cooling suppresses evaporation, while gas-phase natural convection
      acts to enhance evaporation. While the effects of these competing transport
      mechanisms are observed to counterbalance for evaporation on a hydrophobic
      surface, the stronger influence of evaporative cooling on a superhydrophobic
      surface accounts for an overprediction of experimental evaporation rates by ~20%
      with vapor diffusion-based models. The local evaporation fluxes along the liquid
      vapor interface for both hydrophobic and superhydrophobic substrates are
      investigated. The highest local evaporation flux occurs at the three-phase
      contact line region due to proximity to the higher temperature substrate, rather
      than at the relatively colder droplet top; vapor diffusion-based models predict
      the opposite. The numerically calculated evaporation rates agree with
      experimental results to within 2% for superhydrophobic substrates and 3% for
      hydrophobic substrates. The large deviations between past analytical models and
      the experimental data are therefore reconciled with the comprehensive model
      developed here.

PMID- 24320681
TI  - Factors associated with successful completion in an adolescent-only day hospital
      program for eating disorders.
AB  - The purpose of this study was to examine factors associated with completion of an
      adolescent-only eating disorder day hospital program. A total of 65 adolescents
      were included. Completers were compared to non-completers on multiple variables
      including diagnosis, weight, and medication use. Adolescents who completed the
      program were more likely to have been prescribed antidepressants and less likely
      to purge. The two groups did not differ significantly on other variables. Few
      factors differentiated completers from non-completers of the eating disorder day
      hospital program. Further research is needed to determine the role medications or
      purging may play in completing treatment. 

PMID- 24320682
TI  - The association between parity and birthweight in a longitudinal consecutive
      pregnancy cohort.
AB  - BACKGROUND: Nulliparity is associated with lower birthweight, but few studies
      have examined how within-mother changes in risk factors impact this association.
      METHODS: We used longitudinal electronic medical record data from a hospital
      based cohort of consecutive singleton live births from 2002-2010 in Utah. To
      reduce bias from unobserved pregnancies, primary analyses were limited to 9484
      women who entered nulliparous from 2002-2004, with 23,380 pregnancies up to
      parity 3. Unrestricted secondary analyses used 101,225 pregnancies from 45,212
      women with pregnancies up to parity 7. We calculated gestational age and sex
      specific birthweight z-scores with nulliparas as the reference. Using linear
      mixed models, we estimated birthweight z-score by parity adjusting for pregnancy
      specific sociodemographics, smoking, alcohol, prepregnancy body mass index,
      gestational weight gain, and medical conditions. RESULTS: Compared with
      nulliparas', infants of primiparas were larger by 0.20 unadjusted z-score units
      [95% confidence interval (CI) 0.18, 0.22]; the adjusted increase was similar at
      0.18 z-score units [95% CI 0.15, 0.20]. Birthweight continued to increase up to
      parity 3, but with a smaller difference (parity 3 vs. 0 beta = 0.27 [95% CI 0.20,
      0.34]). In the unrestricted secondary sample, there was significant departure in
      linearity from parity 1 to 7 (P < 0.001); birthweight increased only up to parity
      4 (parity 4 vs. 0 beta = 0.34 [95% CI 0.31, 0.37]). CONCLUSIONS: The association
      between parity and birthweight was non-linear with the greatest increase observed
      between first- and second-born infants of the same mother. Adjustment for changes
      in weight or chronic diseases did not change the relationship between parity and
      birthweight.

PMID- 24320683
TI  - Generative topographic mapping-based classification models and their
      applicability domain: application to the biopharmaceutics Drug Disposition
      Classification System (BDDCS).
AB  - Earlier (Kireeva et al. Mol. Inf. 2012, 31, 301-312), we demonstrated that
      generative topographic mapping (GTM) can be efficiently used both for data
      visualization and building of classification models in the initial D-dimensional
      space of molecular descriptors. Here, we describe the modeling in two-dimensional
      latent space for the four classes of the BioPharmaceutics Drug Disposition
      Classification System (BDDCS) involving VolSurf descriptors. Three new
      definitions of the applicability domain (AD) of models have been suggested: one
      class-independent AD which considers the GTM likelihood and two class-dependent
      ADs considering respectively, either the predominant class in a given node of the
      map or informational entropy. The class entropy AD was found to be the most
      efficient for the BDDCS modeling. The predominant class AD can be directly
      visualized on GTM maps, which helps the interpretation of the model. 

PMID- 24320684
TI  - Which patients are not suitable for a subcutaneous ICD: incidence and predictors
      of failed QRS-T-wave morphology screening.
AB  - BACKGROUND: The subcutaneous cardioverter-defibrillator (S-ICD) relies on a pre
      implantation QRS-T morphology screening (TMS) of the ECG to assure that it
      reliably detects the QRS complexes and T waves. The prevalence and clinical
      characteristics of the patients who fail this TMS is unknown. METHODS AND
      RESULTS: QRS-TMS was done in 230 consecutive ICD outpatients (75% male, age 57 +/
      15 years) without an indication for cardiac pacing, using an ECG simulating the
      3 sensing vectors of the S-ICD (TMS-ECG). Patients were defined suitable when at
      least 1 sensing vector was considered appropriate in both supine and standing
      position. In total, 7.4% of patients, who were all male, were considered not
      suitable for a S-ICD according to the TMS-ECG. Independent predictors for TMS
      failure were hypertrophic cardiomyopathy (HCM; odds ratio [OR] 12.6), a heavy
      weight (OR 1.5), a prolonged QRS duration (OR 1.5) and a R:T ratio <3 in the lead
      with the largest T wave on a standard 12-lead surface ECG (OR 14.6). CONCLUSION:
      In patients without an indication for pacing, 7.4% would have been not suitable
      for a S-ICD according to the TMS. HCM, a heavy weight, a prolonged QRS duration
      and a R:T ratio <3 in the ECG lead with the largest T wave were independently
      associated with TMS failure. These data might alert physicians that selection of
      patients for a S-ICD should be considered with special caution in certain patient
      groups, because they may not satisfy ECG criteria for adequate sensing.

PMID- 24320685
TI  - Identification of a novel HLA-A*02 allele, HLA-A*02:06:13, in a Chinese
      individual.
AB  - The novel HLA-A*02:06:13 allele shows one nucleotide difference from A*02:06:01
      in exon 4 at nucleotide position 657 (T->C). 

PMID- 24320686
TI  - Camel milk inhibits inflammatory angiogenesis via downregulation of proangiogenic
      and proinflammatory cytokines in mice.
AB  - Camel milk has traditionally been used to treat cancer, but this practice awaits
      scientific scrutiny, in particular its role in tumor angiogenesis, the key step
      involved in tumor growth and metastasis. We aimed to investigate the effects of
      camel milk on key components of inflammatory angiogenesis in sponge implant
      angiogenesis model. Polyester-polyurethane sponges, used as a framework for
      fibrovascular tissue growth, were implanted in Swiss albino mice and camel milk
      (25, 50 and 100 mg/kg/day) was administered for 14 days through installed
      cannula. The implants collected at day 14 post-implantation were processed for
      the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase
      (NAG), and collagen, which were used as indices for angiogenesis, neutrophil, and
      macrophage accumulation and extracellular matrix deposition, respectively.
      Relevant inflammatory, angiogenic, and fibrogenic cytokines were also determined.
      Camel milk treatment attenuated the main components of the fibrovascular tissue,
      wet weight, vascularization (Hb content), macrophage recruitment (NAG activity),
      collagen deposition and the levels of vascular endothelial growth factor (VEGF),
      interleukin (IL)-1beta, IL-6, IL-17, tumor necrosis factor-alpha, and
      transforming growth factor-beta. A regulatory function of camel milk on multiple
      parameters of the main components of inflammatory angiogenesis has been revealed,
      giving insight into the potential therapeutic benefit underlying the anti-cancer
      actions of camel milk.

PMID- 24320688
TI  - Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa clinical
      strains isolated from western Algeria between 2009 and 2012.
AB  - Infections caused by carbapenem-resistant Pseudomonas aeruginosa strains
      represent a major therapeutic and epidemiological problem. The aim of this study
      was to characterize carbapenem resistance in 89 clinical strains of P. aeruginosa
      isolated from three hospitals in western Algeria between October 2009 and
      November 2012. Minimum inhibitory concentrations (MICs) of imipenem were
      determined by the Etest method. Screening for metallo-beta-lactamase (MbetaL) was
      performed using Etest MbetaL strips, and a PCR was conducted to detect
      carbapenemase-encoding genes. The amplification of the oprD gene followed by a
      sequencing reaction was performed for all strains resistant to imipenem. The
      clonality of 53 P. aeruginosa strains was demonstrated using multilocus sequence
      typing (MLST). Among the 89 isolates, 35 (39.33%) were found to be resistant to
      IMP (MICs >=16 MUg/ml). The blaVIM-2 gene was detected in two strains. The
      remaining imipenem-resistant isolates showed the presence of oprD mutations. The
      MLST analysis differentiated strains into various clones and the strains from the
      same clone had an identical sequence of the oprD gene. We report the second
      detection in 2010 of blaVIM-2 in Algerian P. aeruginosa strains. We also found
      that oprD mutations were the major determinant of high-level imipenem resistance.
      We demonstrate that these oprD mutations can be used as a tool to study the
      clonality in P. aeruginosa isolates.

PMID- 24320687
TI  - Differential polymer structure tunes mechanism of cellular uptake and
      transfection routes of poly(beta-amino ester) polyplexes in human breast cancer
      cells.
AB  - Successful gene delivery with nonviral particles has several barriers, including
      cellular uptake, endosomal escape, and nuclear transport. Understanding the
      mechanisms behind these steps is critical to enhancing the effectiveness of gene
      delivery. Polyplexes formed with poly(beta-amino ester)s (PBAEs) have been shown
      to effectively transfer DNA to various cell types, but the mechanism of their
      cellular uptake has not been identified. This is the first study to evaluate the
      uptake mechanism of PBAE polyplexes and the dependence of cellular uptake on the
      end group and molecular weight of the polymer. We synthesized three different
      analogues of PBAEs with the same base polymer poly(1,4-butanediol diacrylate-co-4
      amino-1-butanol) (B4S4) but with small changes in the end group or molecular
      weight. We quantified the uptake and transfection efficiencies of the pDNA
      polyplexes formulated from these polymers in hard-to-transfect triple negative
      human breast cancer cells (MDA-MB 231). All polymers formed positively charged
      (10-17 mV) nanoparticles of ~200 nm in size. Cellular internalization of all
      three formulations was inhibited the most (60-90% decrease in cellular uptake) by
      blocking caveolae-mediated endocytosis. Greater inhibition was shown with
      polymers that had a 1-(3-aminopropyl)-4-methylpiperazine end group (E7) than the
      others with a 2-(3-aminopropylamino)-ethanol end group (E6) or higher molecular
      weight. However, caveolae-mediated endocytosis was generally not as efficient as
      clathrin-mediated endocytosis in leading to transfection. These findings indicate
      that PBAE polyplexes can be used to transfect triple negative human breast cancer
      cells and that small changes to the same base polymer can modulate their cellular
      uptake and transfection routes. 

PMID- 24320689
TI  - Antimicrobial resistance of Campylobacter jejuni and Campylobacter coli from
      poultry in Italy.
AB  - This study was aimed at assessing the antimicrobial resistance (AMR) of
      Campylobacter isolates from broilers and turkeys reared in industrial farms in
      Northern Italy, given the public health concern represented by resistant
      campylobacters in food-producing animals and the paucity of data about this topic
      in our country. Thirty-six Campylobacter jejuni and 24 Campylobacter coli
      isolated from broilers and 68 C. jejuni and 32 C. coli from turkeys were tested
      by disk diffusion for their susceptibility to apramycin, gentamicin,
      streptomycin, cephalothin, cefotaxime, ceftiofur, cefuroxime, ampicillin,
      amoxicillin+clavulanic acid, nalidixic acid, flumequine, enrofloxacin,
      ciprofloxacin, erythromycin, tilmicosin, tylosin, tiamulin, clindamycin,
      tetracycline, sulfamethoxazole+trimethoprim, chloramphenicol. Depending on the
      drug, breakpoints provided by Comite de l'antibiogramme de la Societe Francaise
      de Microbiologie, Clinical and Laboratory Standards Institute, and the
      manufacturer were followed. All broiler strains and 92% turkey strains were
      multidrug resistant. Very high resistance rates were detected for quinolones,
      tetracycline, and sulfamethoxazole+trimethoprim, ranging from 65% to 100% in
      broilers and from 74% to 96% in turkeys. Prevalence of resistance was observed
      also against ampicillin (97% in broilers, 88% in turkeys) and at least three
      cephalosporins (93-100% in broilers, 100% in turkeys). Conversely, no isolates
      showed resistance to chloramphenicol and tiamulin. Susceptibility prevailed for
      amoxicillin+clavulanic acid and aminoglycosides in both poultry species, and for
      macrolides and clindamycin among turkey strains and among C. jejuni from
      broilers, whereas most C. coli strains from broilers (87.5%) were resistant.
      Other differences between C. jejuni and C. coli were observed markedly in broiler
      isolates, with the overall predominance of resistance in C. coli compared to C.
      jejuni. This study provides updates and novel data on the AMR of broiler and
      turkey campylobacters in Italy, revealing the occurrence of high resistance to
      several antimicrobials, especially key drugs for the treatment of human
      campylobacteriosis, representing a potential risk for public health. 

PMID- 24320690
TI  - Interval training does not modulate diastolic function in heart transplant
      recipients.
AB  - OBJECTIVES: This study investigates the effect of aerobic interval training on
      diastolic function at rest and during exercise in stable heart transplant (HTx)
      recipients. DESIGN: Twenty-three stable HTx recipients (74% males, mean age 50 +/
      14.9 years) were recruited to a training programme. Intervention was 8 weeks
      intensive training or control in a randomized controlled design. RESULTS: At
      baseline, participants had normal or mild diastolic dysfunction at rest. During
      exercise, mean E/e' increased from 9.0 (+/- 2.8) to 12.8 (+/- 7.7) (p = 0.09),
      E/A increased from 2.1 (+/- 0.6) to 2.6 (+/- 0.7) (p = 0.02), and deceleration
      time decreased by over 50 ms, all markers of increased filling pressure. There
      were no correlations between diastolic function and VO 2 peak at baseline. After
      intervention VO 2 peak increased from 23.9 (+/- 4.5) to 28.3(+/- 6) ml/kg/min in
      the training group (difference between groups p = 0.0018). No consistent pattern
      of improvement in diastolic function at rest or during exercise was seen.
      CONCLUSION: The study does not support a role of diastolic dysfunction in the
      limited exercise capacity of HTx recipients and suggests that in these patients
      peripheral factors are of greater importance.

PMID- 24320691
TI  - Association of homocysteine with type 2 diabetes: a meta-analysis implementing
      Mendelian randomization approach.
AB  - BACKGROUND: We tested the hypothesis that elevated homocysteine (Hcy) level is
      causally associated with increased risk of type 2 diabetes mellitus (T2DM).
      RESULTS: The meta-analysis and Mendelian randomization analysis were performed
      among 4011 cases and 4303 controls. The absolute pooled mean Hcy concentration in
      subjects with MTHFR 677TT was 5.55 MUmol/L (95% CI, 1.33 to 9.77) greater than
      that in subjects with MTHFR 677CC in T2DM. Overall, the T allele of the MTHFR 677
      C > T conferred a greater risk for T2DM [Random effect (RE) OR = 1.31(1.17-1.64),
      I2 = 41.0%, p = 0.055]. The random effect (RE) pooled OR associated with T2DM for
      MTHFR 677TT relative to the 677CC was [RE OR = 1.38(1.18-1.62)]. The fixed-effect
      pooled OR of the association for the MTHFR 677 TT vs CT was 1.29 (95% CI, 1.09
      1.51). MTHFR 677 TT showed a significantly higher risk for T2DM compared with
      MTHFR 677 CC + CT [Fixed effect (FE) OR = 1.32(1.14-1.54), I2 = 0.0%, p = 0.686].
      The absolute pooled mean Hcy concentration in individuals with T2DM was 0.94
      MUmol/L (95% CI, 0.40-1.48) greater than that in control subjects. The estimated
      causal OR associated with T2DM was 1.29 for 5 MUmol/L increment in Hcy.
      CONCLUSIONS: Our findings provided strong evidence on the causal association of
      Hcy level with the development of T2DM.

PMID- 24320692
TI  - SMALL GRAIN 1, which encodes a mitogen-activated protein kinase kinase 4,
      influences grain size in rice.
AB  - Although grain size is one of the most important components of grain yield,
      little information is known about the mechanisms that determine final grain size
      in crops. Here we characterize rice small grain1 (smg1) mutants, which exhibit
      small and light grains, dense and erect panicles and comparatively slightly
      shorter plants. The short grain and panicle phenotypes of smg1 mutants are caused
      by a defect in cell proliferation. The smg1 mutations were identified, using a
      map-based cloning approach, in mitogen-activated protein kinase kinase 4
      (OsMKK4). Relatively higher expression of OsMKK4/SMG1 was detected in younger
      organs than in older ones, consistent with its role in cell proliferation. Green
      fluorescent protein (GFP)-OsMKK4/SMG1 fusion proteins appear to be distributed
      ubiquitously in plant cells. Further results revealed that OsMKK4 influenced
      brassinosteroid (BR) responses and the expression of BR-related genes. Thus, our
      findings have identified OsMKK4 as a factor for grain size, and suggest a
      possible link between the MAPK pathways and BRs in grain growth.

PMID- 24320693
TI  - Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2-
      and P450 2E1-knockout mouse liver and lung microsomes.
AB  - Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent
      metabolic activation. P450 2E1 and P450 2F2 are considered to be two main
      cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective
      of the current study was to determine the correlation between the formation of
      styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary
      toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic
      decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2
      null mouse lung microsomes relative to that in the wild-type mouse lung
      microsomes; however, no significant difference in the production of the styrene
      metabolites was observed between lung microsomes obtained from Cyp2e1-null and
      the wild-type mice. The knockout and wild-type mice were treated with styrene
      (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage
      fluids were monitored to evaluate the pulmonary toxicity induced by styrene.
      Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar
      to that of the wild-type animals; however, Cyp2f2-null mice were resistant to
      styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are
      responsible for the metabolic activation of styrene. The latter enzyme plays an
      important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4
      vinylphenol are suggested to participate in the development of lung injury
      induced by styrene. 

PMID- 24320694
TI  - Controlled porosity osmotic pump system for the delivery of diclofenac sodium: in
      vitro and in-vivo evaluation.
AB  - The objective of this study was to develop controlled porosity osmotic pump
      (CPOP) tablets of diclofenac sodium (DS). The influence of different cores
      (polymers and osmogens) and coats (thickness and porosigen content) on DS release
      were studied. Results revealed that decreasing HPMC viscosity grade from 4000cp
      (K4M) to 15cp (E15) increased DS release. While increasing the tablet coat
      thickness decreased DS release. The presence of osmogen increased DS release in
      the following rank: mannitol > lactose > avicel. There was a direct relationship
      between increasing PEG-400 in the coating solution and the amount of drug
      released in all formulations studied, except in one condition. A comparative
      bioavailability study using a selected CPOP formulation (T) versus the innovator
      product (R) revealed that CPOP tablet maintained a less fluctuated DS plasma
      concentration for up to 24 h with a detected mean Cmax of 836.8 +/- 142.4 and
      445.0 +/- 81.0 ng/mL for R and T, respectively. There were no statistically
      significant differences between R and T, concerning AUC0-24 and AUC0-infinity.
      Moreover, the appearance of the multi-peak phenomenon, which is frequently
      observed with DS absorption, was found in only 25% of volunteers in case of T
      versus 75% in case of R.

PMID- 24320695
TI  - Functional magnetic stimulation using a parabolic coil for dysphagia after
      stroke.
AB  - OBJECTIVES: Recently, the usefulness of neuromuscular electrical stimulation and
      repetitive transcranial magnetic stimulation for poststroke dysphagia has been
      reported. However, there is no report that describes the effectiveness of
      functional magnetic stimulation (FMS) for dysphagia. The purpose of this study is
      to clarify the effectiveness of FMS for poststroke dysphagia. METHODS: Twenty
      poststroke dysphagic patients (age at treatment: 51-80 years; interval between
      onset of stroke and treatment: 6 to 36 months) were randomly assigned to a real
      group or a sham group. In the real group, FMS of 30 Hz was applied for suprahyoid
      muscles in a 20-sec train using a parabolic coil for 10 min (total 1200 pulses).
      In the sham group, sham stimulation was applied for 10 min at the same site.
      Swallowing function was evaluated by the timed water swallow test, interswallow
      interval (ISI), swallowing volume velocity (speed), and volume per swallow
      (capacity) were measured before and after stimulation. RESULTS: All patients
      completed the stimulation and none showed any adverse reactions throughout the
      stimulation. The improvement of speed and capacity of swallowing after
      stimulation was significantly larger in the real group compared with the sham
      group (all p < 0.05). However, no significant difference in the ISI was found
      between the groups. CONCLUSIONS: FMS using a parabolic coil can potentially
      improve swallowing function in poststroke dysphagic patients.

PMID- 24320696
TI  - Facile method for fabricating flexible substrates with embedded, printed silver
      lines.
AB  - Insertion, curing and delamination is presented as a simple and scalable method
      for creating flexible substrates with embedded, printed silver lines. In a
      sequential process, aerosol-jet printed silver lines are transferred from a donor
      substrate to a thin reactive polymer that is directly adhered to a flexible
      substrate. Due to the unique ability of the aerosol jet to print continuous lines
      on a low energy surface, a 100% transfer of the printed electrodes is obtained,
      as confirmed by electrical measurements. Moreover, the root-mean-square roughness
      of the embedded electrodes is less than 10 nm, which is much lower than that for
      their as-printed form. The embedded electrodes are robust and do not show a
      significant degradation in electrical performance after thousands of bending
      cycles. 

PMID- 24320697
TI  - Photoinhibition of cyanobacteria and its application in cultural heritage
      conservation.
AB  - Light has bilateral effects on phototrophic organisms. As cyanobacteria in Roman
      hypogea are long acclimatized to dim environment, moderate intensity of
      illumination can be used to alleviate biodeterioration problems on the stone
      substrata. Moderate intensity of light inactivates cyanobacteria by causing
      photoinhibition, photobleaching and photodamage to the cells. The effectiveness
      of light depends not only on its intensity but also on the composition and
      pigmentation of the component cyanobacteria in the biofilms. Red light is the
      most effective for the species rich in phycocyanin and allophycocyanin, such as
      Leptolyngbya sp. and Scytonema julianum, whereas green light is effective to
      inhibit the species rich in phycoerythrin, like Oculatella subterranea. White
      light is effective to control the grayish and the black cyanobacteria, such as
      Symphyonemopsis sp. and Eucapsis sp. abundant in all of these pigments. Blue
      light is the least effective. 150 MUmol photons m(-2)  s(-1) of blue light cannot
      cause biofilm damage while the same intensity of red, green or white irradiation
      for 14 days can severely damage the cyanobacterial cells in the biofilms due to
      ROS formation. Electron spin resonance spectroscopy detected the formation of
      radicals in different cyanobacterial cellular extracts exposed to 80 MUmol
      photons m(-2)  s(-1) of light. 

PMID- 24320698
TI  - Clinical considerations on Buruli ulcer employing two molecular tests for the
      detection of Mycobacterium ulcerans in 100 skin biopsies.
AB  - OBJECTIVES: Buruli ulcer (BU) is an infected cutaneous lesion, the etiological
      agent of which is Mycobacterium ulcerans. Diagnosis is confirmed by the
      identification of acid-fast bacilli and culture. In clinically suspicious forms
      with negative bacteriological or Ziehl-Neelsen (ZN) findings, molecular tests are
      used. This study compared the concordance of nested polymerase chain reaction
      (PCR) (targeting IS2404) and PCR (targeting IS2606) in different clinical
      situations. METHODS: A total of 57 samples were sourced from 39 BU patients.
      Control samples (n = 43) were obtained from non-BU ulcers in 38 patients. Samples
      were divided into two pieces and submitted to, respectively, histological
      examination and ZN staining, and PCR. Subsamples submitted to PCR were divided
      and submitted to nested PCR IS2404 and PCR IS2606, respectively. RESULTS: Of the
      57 BU biopsies, positive results were obtained by nested PCR in 18 (31.6%) and by
      IS2606 PCR in 37 (64.9%) cases. Sequencing of the positive samples confirmed the
      specificity of amplicons in all nested PCR samples and in 26 of 37 (70.2%)
      samples positive to IS2606. Hence, nested PCR was more specific (100% vs. 93%)
      and less sensitive (32% vs. 46%) than IS2606 PCR. In the BU samples, nested PCR
      was negative in 15 instances, and IS2606 PCR was negative in 11 instances in
      which ZN histology had been positive (false negatives). Both PCRs were positive
      in six ZN-negative smears. CONCLUSIONS: We considered 57 samples from 39 BU
      patients in various clinical stages and at different times after the beginning of
      therapy. These provided positive results in 18 cases with IS2404 nested PCR and
      in 37 cases with PCR IS2606; only 26 of the latter remained positive subsequent
      to sequencing. Hence, even if IS2404 PCR is considered more specific, in subjects
      who appear to fail to respond to therapy, it is advisable to also carry out
      IS2606 PCR. A possible interpretation of the discordance between the two
      techniques due to unavoidable technical errors as well as to different
      sensitivity of the two tests at M. ulcerans DNA low concentration (i.e. in recent
      infection and in well-treated cases) is discussed.

PMID- 24320699
TI  - An historical account of dermatology in Buddhist Sri Lankan literature.

PMID- 24320700
TI  - Cardiovascular safety of sulphonylurea: comment on the study by Monami et al.

PMID- 24320701
TI  - Prostate stem cell antigen - novel biomarker and therapeutic target?
AB  - Prostate stem cell antigen gene was originally identified through an analysis of
      genes upregulated in the human prostate cancer LAPC-4 xenograft model. PSCA was
      named inaccurately since it is not a marker for a stem cell population nor is it
      exclusively expressed in the prostate. The function of PSCA in normal cellular
      processes or carcinogenesis is currently unknown. 

PMID- 24320702
TI  - Surface structural dynamics of enzymatic cellulose degradation, revealed by
      combined kinetic and atomic force microscopy studies.
AB  - Highly heterogeneous and usually weakly defined substrate morphologies complicate
      the study of enzymatic cellulose hydrolysis. The cellulose surface has a non
      uniform shape in particular, with consequent impacts on cellulase adsorption and
      activity. We have therefore prepared a cellulosic model substrate which is shown
      by atomic force microscopy (AFM) to display a completely smooth surface, the
      residual squared mean roughness being 10 nm or lower, and applied it for kinetic
      analysis of cellulase action. The substrate consists of an amorphous cellulose
      matrix into which variably sized crystalline fibers are distributed in apparently
      irregular fashion. Its conversion into soluble sugars by Trichoderma sp.
      cellulase at 50  degrees C proceeded without apparent limitation up to 70%
      completion and was paralleled by a steady increase in cellulase adsorption to the
      cellulose. Individual cellulase components (CBH I, CBH II, EG) also showed
      strongly enhanced adsorption with progressing cellulose conversion, irrespective
      of their preference for degrading the amorphous or crystalline substrate parts as
      revealed by AFM. The specific activity of the adsorbed cellulases, however,
      decreased concomitantly. Cellulose surface morphologies evolving as a consequence
      of cellulase action were visualized by AFM. Three-dimensional surface degradation
      by the cellulases resulted in a large increase in cellulose surface area for
      enzyme adsorption. However, the decline in enzyme specific activity during
      conversion was caused by factors other than surface ablation and disruption.
      Based on kinetic evidence for enzymatic hydrolyses of the smooth-surface model
      substrate and microcrystalline cellulose (Avicel), we hypothesize that, due to
      gradual loss of productive dynamics in their interactions with the cellulose
      surface, individual cellulases get progressively confined to substrate parts
      where they are no longer optimally active. This eventually leads to an overall
      slow-down of hydrolysis. 

PMID- 24320703
TI  - An insight into the ribonucleolytic and antiangiogenic activity of buffalo
      lactoferrin.
AB  - Lactoferrin (LF) has several biological effects ranging from ribonuclease
      activity to antiangiogenic activity. It thus serves as a potential target protein
      for studies related to ribonucleolytic activity in association with its
      antiangiogenic activity. We have isolated buffalo LF and checked the
      ribonucleolytic activity via an agarose gel-based assay and precipitation assay.
      The ribonucleolytic activity of LF is lower compared to RNase A and the pH
      profile is a bell-shaped curve, with a pK1 value of 5.43 and pK2 of 7.65. The
      ribonuclease inhibitor that inhibits many ribonuclease-type proteins by forming a
      tight complex is unable to inhibit the ribonucleolytic property of LF. Fe(III)
      behaves as a noncompetitive inhibitor for the ribonucleolytic activity of
      protein. The superoxide-scavenging activity of the protein has also been
      measured. Histidine modification by diethylpyrocarbonate was monitored by UV-Vis
      spectroscopy at pH 7 and pH 8 and the effect towards the ribonucleolytic activity
      was determined. The antiangiogenic property of LF was investigated by the
      chorioallantoic membrane assay. Finally, the possible active site was analyzed
      via docking studies and correlated with the experimental study. 

PMID- 24320704
TI  - Are there any differences in psychiatric symptoms and eating attitudes between
      pregnant women with hyperemesis gravidarum and healthy pregnant women?
AB  - AIM: We aimed to determine the relationship between eating attitudes and
      psychiatric symptoms in women with hyperemesis gravidarum (HG) and to compare
      these women with healthy control subjects. METHODS: The study sample included 48
      women with HG, and the control group had 44 pregnant women. The patients were
      selected from women with HG hospitalized in the obstetric inpatient clinic. All
      of the participants were in the first trimester of pregnancy. The participants'
      sociodemographic and clinical characteristics were recorded in the obstetric
      clinic. All of the participants completed a Beck Depression Inventory (BDI), Beck
      Anxiety Inventory (BAI), Eating Attitudes Test (EAT) and Body Image Scale (BIS).
      RESULTS: Women with HG were more likely to have had a history of HG during their
      previous pregnancy (P<0.05). There was no significant difference between the
      study and control groups regarding obstetric history. Women with HG were more
      influenced by food that induced nausea. There was no significant difference
      between the study and control groups for pre-pregnancy nausea, food craving and
      the initial BMI (P>0.05). Depression and anxiety scores were significantly higher
      in women with HG (P<0.05). However, there was no significant difference between
      the study and control groups for body image score and eating attitude test scores
      (P>0.05). CONCLUSION: We suggest that HG appears to be associated with depression
      and anxiety symptoms rather than deterioration of eating attitudes and body
      image. However, these results should be confirmed by prospective and clinical
      studies.

PMID- 24320705
TI  - A cyanide-bridged molybdenum bis(maleonitriledithiolate) square.
AB  - [Et4N]2[Mo(IV)O(mnt)2] (mnt = maleonitriledithiolate) reacts, as a synthon, with
      Me3SiCN under an acidic medium to produce the square complex [Et4N]4[Mo4(MU
      CN)4(mnt)8] (1) in high yield. Complex 1 shows strong antiferromagnetic
      interactions between adjacent Mo atoms in the cluster. The presence of redox
      active mnt as a capping ligand strongly influences the magnetic property of 1.
      The physicochemical properties of 1 have been rationalized by density functional
      theory level of calculations. 

PMID- 24320706
TI  - Brain death increases COX-1 and COX-2 expression in the renal medulla in a pig
      model.
AB  - BACKGROUND: Brain death is linked to a systemic inflammatory response that
      includes prostaglandins and cytokines among its mediators. The levels of
      cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) affect graft survival,
      but it remains unknown whether these enzymes are modified during brain death. The
      aims of this study were to investigate the organ expression of COX and to analyse
      the cytokine response in the plasma, cerebrospinal fluid (CSF), and organs in a
      porcine model of intracerebral haemorrhage and brain death. METHODS: Twenty pigs
      were randomly assigned to either a brain death group or a control group. Brain
      death was induced by an intracerebral injection of blood, and the animals were
      observed over the next 8 h. Tissue samples were tested for COX-1, COX-2 messenger
      RNA (mRNA) expression (heart, lung, and kidney), haeme oxygenase-1 (HO-1)
      (kidney), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10, and tumour necrosis
      factor-alpha. These cytokines were also measured at eight time points in the
      plasma and CSF. RESULTS: At the organ level, the levels of COX-1 and COX-2 mRNA
      expression were increased only in the renal medulla (P = 0.03 and P = 0.02,
      respectively). The cytokine levels in the tissue, plasma, and CSF revealed no
      differences between the groups. HO-1 expression decreased (P = 0.0088).
      CONCLUSION: Brain death increases the expression of COX-1 and COX-2 mRNA in the
      renal medulla. The release of cytokines into the plasma and CSF did not vary
      between the groups.

PMID- 24320707
TI  - Shape and size control of Cu nanoparticles by tailoring the surface morphologies
      of TiN-coated electrodes for biosensing applications.
AB  - A method for controlling the shapes and sizes of Cu nanoparticles during
      electrodeposition has been developed by tailoring the surface morphologies of TiN
      coated electrodes. Larger octahedral Cu NPs grew on a granular TiN film; smaller,
      irregular Cu NPs formed on a pyramidal TiN film. The surface morphology of the
      TiN film affected the accumulation of Cu(2+) and hexadecyltrimethylammonium
      (CTA(+)) ions, leading to the different shapes and sizes of the resulting Cu NPs.
      The significant steric effect of the CTA(+) ions was confirmed when using the
      film of pyramidal TiN as the electrode in the CTAB-containing electrolyte; it
      contributed to the growth of the smaller, irregular Cu NPs. The sensitivity of
      the smaller, irregular Cu NPs in the detection of glucose was better than that of
      the larger, octahedral Cu NPs because of the former's greater increase in the
      Cu(2+)-to-Cu(0) ratio. 

PMID- 24320708
TI  - Enhanced electron transport in Nb-doped TiO2 nanoparticles via pressure-induced
      phase transitions.
AB  - Anatase TiO2 is one of the most important energy materials but suffers from poor
      electrical conductivity. Nb doping has been considered as an effective way to
      improve its performance in the applications of photocatalysis, solar cells, Li
      batteries, and transparent conducting oxide films. Here, we report the further
      enhancement of electron transport in Nb-doped TiO2 nanoparticles via pressure
      induced phase transitions. The phase transition behavior and influence of Nb
      doping in anatase Nb-TiO2 have been systematically investigated by in situ
      synchrotron X-ray diffraction and Raman spectroscopy. The bulk moduli are
      determined to be 179.5, 163.3, 148.3, and 139.0 GPa for 0, 2.5, 5.0, and 10.0 mol
      % Nb-doped TiO2, respectively. The Nb-concentration-dependent stiffness variation
      has been demonstrated: samples with higher Nb concentrations have lower
      stiffness. In situ resistance measurements reveal an increase of 40% in
      conductivity of quenched Nb-TiO2 in comparison to the pristine anatase phase. The
      pressure-induced conductivity evolution is discussed in detail in terms of the
      packing factor model, which provides direct evidence for the rationality of the
      correlation of packing factors with electron transport in semiconductors.
      Pressure-treated Nb-doped TiO2 with unique properties surpassing those in the
      anatase phase holds great promise for energy-related applications. 

PMID- 24320710
TI  - Use of emergency departments and primary care visits for asthma related
      conditions in the 3 years following an asthma education program.
AB  - BACKGROUND: This study examines changes in Primary Care Visits (PCVs) and
      Emergency Department Visits (EDVs) among 1918 patients with asthma who attended
      either two visits, one visit or were no-show referrals at the Dr. Patrick Gill
      Asthma Education Center (AEC) in Charlottetown Prince Edward Island (PEI) between
      January 1, 2003 and March 31, 2008 compared to 2799 controls selected from a list
      of PEI asthma patients developed for the Canadian Chronic Disease Surveillance
      System (CCDSS). METHODS: Hurdle regression was used to model counts of PCVs and
      negative binomial models were used to model counts of EDVs at 12 months prior to
      AEC contact and 0-1, >1 to 2 and >2 to 3 years after AEC contact. The PEI
      Research Board approved the project. RESULTS: No-show referrals had a significant
      increase in pediatric EDVs and PCVs in the first year after referral. The higher
      rates of PCVs and EDVs prior to contact with the AEC in patients referred to the
      AEC were reduced after contact with the AEC, although they remained significantly
      higher than the CCDSS controls. CONCLUSIONS: Compared to patients who attended
      the AEC, referred patients who did not attend the AEC did not achieve similar
      reductions in pediatric EDVs and PCVs in the first year after referral.

PMID- 24320709
TI  - Single parent households and increased child asthma morbidity.
AB  - OBJECTIVES: To characterize whether single parent households are associated with
      pediatric asthma-related repeat healthcare utilization and to examine family
      level psychosocial variables that may explain this relationship. METHODS: We
      analyzed a prospective cohort of 526 children aged 1-16 years hospitalized for
      asthma or bronchodilator-responsive wheezing whose caregivers self-reported their
      marital status. Those reporting being "single" were considered the at-risk
      category. The outcome was repeat asthma-related utilization (emergency room (ER)
      revisit or hospital readmission) within 12 months. We assessed, a priori, four
      psychosocial variables (household income, caregiver risk of psychological
      distress, ratio of in-home children to adults, and regular attendance at
      childcare or a secondary home). RESULTS: Among all children enrolled in the
      cohort, 40% returned to the ER or hospital for asthma within 12 months. Of all
      caregivers, 59% self-identified as single. Single status was significantly
      associated with each psychosocial variable. Children in households with lower
      incomes and higher ratios of children to adults were both more likely to return
      to the ER or hospital than children with higher incomes and lower ratios,
      respectively (each p < 0.05). Patients in single parent households were
      significantly more likely to reutilize than those in married parent households
      (OR 1.44, 95% CI 1.00-2.07, p < 0.05). When adjusted for income, the relationship
      between single parent households and reutilization became non-significant.
      CONCLUSIONS: Children admitted for asthma from single parent households were more
      likely to have asthma-related reutilization within 12 months than children from
      homes with married parents. This was driven, in large part, by underlying
      differences in household income.

PMID- 24320711
TI  - The emerging field of affective science.
AB  - This commentary discusses the emerging field of affective science. The authors
      note that there have been more publications containing the phrase "affective
      science" in the past few years than in all prior years combined. The importance
      accorded to this field is evidenced by the attention it is now receiving in our
      field's highest tier journals, most notably right here in the pages of Emotion,
      as well as in the several dozen recent volumes on affective science, not to
      mention the growing number of journals dedicated to research in affective
      science. To provide an integrated professional home for the emerging field of
      affective science, the Society for Affective Science was founded in 2012, and
      will host its first meeting in April 2014 in Washington DC. The authors remark
      that these are exciting times in affective science, and it is very clear that the
      best is yet to come.

PMID- 24320712
TI  - Don't start what you can't stop: differentiating individual differences in
      ruminative onset and ruminative persistence, and their contributions to
      dysphoria.
AB  - There is much evidence to suggest that rumination and dysphoria share a close
      relationship. The tendency to ruminate is considered a stable individual
      difference, reflecting variation in repetitive thoughts concerning the causes and
      consequences of distress. In the present study, we evaluated the veracity of a
      proposed distinction between 2 hypothetical dimensions of ruminative tendency,
      which plausibly represent dissociable facets of dispositional rumination, and
      whose interactive influence may make a particularly strong contribution to
      dysphoria. These dimensions are ruminative onset, the probability of experiencing
      ruminative symptoms when feeling upset, and ruminative persistence, the
      continuation of ruminative symptoms once initiated. The findings indicate that
      ruminative onset and ruminative persistence do indeed represent dissociable
      dimensions of ruminative disposition. Furthermore, as hypothesized, it is the
      interaction between these 2 facets of rumination that makes the greatest
      contribution to the prediction of variance in dysphoria.

PMID- 24320713
TI  - Role of adolescent and maternal depressive symptoms on transactional emotion
      recognition: context and state affect matter.
AB  - Depressive symptomatology is associated with impaired recognition of emotion.
      Previous investigations have predominantly focused on emotion recognition of
      static facial expressions neglecting the influence of social interaction and
      critical contextual factors. In the current study, we investigated how youth and
      maternal symptoms of depression may be associated with emotion recognition biases
      during familial interactions across distinct contextual settings. Further, we
      explored if an individual's current emotional state may account for youth and
      maternal emotion recognition biases. Mother-adolescent dyads (N = 128) completed
      measures of depressive symptomatology and participated in three family
      interactions, each designed to elicit distinct emotions. Mothers and youth
      completed state affect ratings pertaining to self and other at the conclusion of
      each interaction task. Using multiple regression, depressive symptoms in both
      mothers and adolescents were associated with biased recognition of both positive
      affect (i.e., happy, excited) and negative affect (i.e., sadness, anger,
      frustration); however, this bias emerged primarily in contexts with a less strong
      emotional signal. Using actor-partner interdependence models, results suggested
      that youth's own state affect accounted for depression-related biases in their
      recognition of maternal affect. State affect did not function similarly in
      explaining depression-related biases for maternal recognition of adolescent
      emotion. Together these findings suggest a similar negative bias in emotion
      recognition associated with depressive symptoms in both adolescents and mothers
      in real-life situations, albeit potentially driven by different mechanisms.

PMID- 24320714
TI  - Expression and prognostic significance of Oct4 and Nanog in neuroblastoma.
AB  - Neuroblastoma is the most common extracranial solid tumor of children, accounting
      for an estimated 15% cancer-related deaths in this period. It has been
      hypothesized that drug resistance of cancer stem cells may be responsible for
      chemotherapy failure, sustained tumor growth, and recurrence in many solid
      tumors. In this study, we investigated the expression of Octamer-binding
      transcription factor 4 (Oct4) and Nanog, two stem cell markers, in 47
      neuroblastic tumors by immunohistochemistry and correlated their expression by
      other prognostic factors especially with NMYC amplification using both
      fluorescent and chromogenic in situ hybridization methods. Twenty three cases
      (48.9%) showed Oct4 signals and eight cases (17%) showed Nanog expression. All
      Nanog positive tumors showed Oct4 expression. Seven cases (14.1%) had NMYC
      amplification. There was also no association between positive Oct4 and Nanog
      reactivity and tumor morphology, age, mitosis-karyorrhexis index, NMYC
      amplification, favorable or unfavorable histology, and risk groups (p > 0.05).
      Cancer stem cells hypothesis is a challenging issue and controversies exist about
      their significance. Although our study did not show strong association between
      prognostic factors and expression of stem cell markers, performing of further
      large-scale studies of various neuroblastic tumors with various stages is
      suggested. 

PMID- 24320715
TI  - Acting to let someone die.
AB  - This paper examines the recent prominent view in medical ethics that withdrawing
      life-sustaining treatment (LST) is an act of killing. I trace this view to the
      rejection of the traditional claim that withdrawing LST is an omission rather
      than an act. Although that traditional claim is not as problematic as this recent
      prominent view suggests, my main claim is that even if we accepted that
      withdrawing LST should be classified as an act rather than as an omission, it
      could still be classified as letting die rather than killing. Even though
      omissions are contrasted with acts, letting die need not be, for one can let die
      by means of acts. The remainder of the paper is devoted to establishing this
      claim and addresses certain objections to it. 

PMID- 24320716
TI  - Thin or overweight women's fat talk: which is worse for other women's body
      satisfaction?
AB  - Fat talk is not merely correlated with, but appears to be one of the causes of
      body dissatisfaction in other women. Moderators of fat talk's deleterious
      effects, however, have not yet been identified. This experiment tested whether
      the body type of the fat-talker affects listeners' body satisfaction. Women
      viewed photos of either noticeably thin or overweight women making either fat
      talk or positive body statements. Fat talk by thin and overweight women both had
      a negative impact on women's body satisfaction, but dissatisfaction was highest
      after exposure to photos of thin women making fat talk statements. Statistically
      indistinguishable from this latter effect, however, was the negative effect of
      thin women making positive body statements. Results are considered within a
      social comparison framework. Theoretical implications for the thin-ideal and fat
      talk literatures are presented, as are clinical implications for work with
      clients. 

PMID- 24320717
TI  - Pleistocene Chinese cave hyenas and the recent Eurasian history of the spotted
      hyena, Crocuta crocuta.
AB  - The living hyena species (spotted, brown, striped and aardwolf) are remnants of a
      formerly diverse group of more than 80 fossil species, which peaked in diversity
      in the Late Miocene (about 7-8 Ma). The fossil history indicates an African
      origin, and morphological and ancient DNA data have confirmed that living spotted
      hyenas (Crocuta crocuta) of Africa were closely related to extinct Late
      Pleistocene cave hyenas from Europe and Asia. The current model used to explain
      the origins of Eurasian cave hyena populations invokes multiple migrations out of
      Africa between 3.5-0.35 Ma. We used mitochondrial DNA sequences from radiocarbon
      dated Chinese Pleistocene hyena specimens to examine the origin of Asian
      populations, and temporally calibrate the evolutionary history of spotted hyenas.
      Our results support a far more recent evolutionary timescale (430-163 kya) and
      suggest that extinct and living spotted hyena populations originated from a
      widespread Eurasian population in the Late Pleistocene, which was only
      subsequently restricted to Africa. We developed statistical tests of the
      contrasting population models and their fit to the fossil record. Coalescent
      simulations and Bayes Factor analysis support the new radiocarbon-calibrated
      timescale and Eurasian origins model. The new Eurasian biogeographic scenario
      proposed for the hyena emphasizes the role of the vast steppe grasslands of
      Eurasia in contrast to models only involving Africa. The new methodology for
      combining genetic and geological data to test contrasting models of population
      history will be useful for a wide range of taxa where ancient and historic
      genetic data are available.

PMID- 24320718
TI  - Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective
      multicenter study.
AB  - OBJECTIVES: The goal of this study was to evaluate the long-term efficacy and
      safety of peripheral nerve field stimulation (PNFS) for chronic low back pain
      (cLBP). MATERIALS AND METHODS: In this prospective, multicenter observational
      study, 118 patients were admitted to 11 centers throughout Austria and
      Switzerland. After a screening visit, all patients underwent a trial stimulation
      period of at least seven days before implantation of the permanent system. Leads
      were placed in the subcutaneous tissues of the lower back directly in the region
      of greatest pain. One hundred five patients were implanted with a permanent
      stimulating system. Patients' evaluation of pain and functional levels were
      completed before implantation and one, three, and six months after implantation.
      Adverse events, medication usage, and coverage of the painful area and predictive
      value of transcutaneous electrical nerve stimulation (TENS) were monitored.
      RESULTS: All pain and quality-of-life measures showed statistically significant
      improvement during the treatment period. These included the average pain visual
      analog scale, the Oswestry Disability Questionnaire, the Becks Depression
      Inventory, and the Short Form-12 item Health survey. Additionally, medication
      usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants
      showed a highly significant reduction. Complications requiring surgical
      intervention were reported in 9.6% of the patients. The degree of coverage of
      painful areas seems to be an important criterion for efficacy of PNFS, whereas
      TENS is presumably no predictor. CONCLUSIONS: This prospective, multicenter study
      confirms that PNFS is an effective therapy for the management of cLBP.
      Significant improvements in many aspects of the pain condition were measured, and
      complications were minimal.

PMID- 24320719
TI  - On the nanoengineering of superhydrophobic and impalement resistant surface
      textures below the freezing temperature.
AB  - The superhydrophobic behavior of nano- and microtextured surfaces leading to
      rebound of impacting droplets is of great relevance to nature and technology. It
      is not clear however, if and under what conditions this behavior is maintained
      when such surfaces are severely undercooled possibly leading to the formation of
      frost and icing. Here we elucidate key aspects of this phenomenon and show that
      the outcome of rebound or impalement on a textured surface is affected by air
      compression underneath the impacting drop and the time scale allowing this air to
      escape. Remarkably, drop impalement occurred at identical impact velocities, both
      at room and at very low temperatures (-30  degrees C) and featured a ringlike
      liquid meniscus penetration into the surface texture with an entrapped air bubble
      in the middle. At low temperatures, the drop contact time and receding dynamics
      of hierarchical surfaces were profoundly influenced by both an increase in the
      liquid viscosity due to cooling and a partial meniscus penetration into the
      texture. For hierarchical surfaces with the same solid fraction in their
      roughness, minimizing the gap between the asperities (both at micro- and
      nanoscales) yielded the largest resistance to millimetric drop impalement. The
      best performing surface impressively showed rebound at -30  degrees C for drop
      impact velocity of 2.6 m/s. 

PMID- 24320720
TI  - Physiological and molecular characterization of Si uptake in wild rice species.
AB  - Cultivated rice (Oryza sativa) accumulates high concentration of silicon (Si),
      which is required for its high and sustainable production. High Si accumulation
      in cultivated rice is achieved by a high expression of both influx (Lsi1) and
      efflux (Lsi2) Si transporters in roots. Herein, we physiologically investigated
      Si uptake, isolated and functionally characterized Si transporters in six wild
      rice species with different genome types. Si uptake by the roots was lower in
      Oryza rufipogon, Oryza barthii (AA genome), Oryza australiensis (EE genome) and
      Oryza punctata (BB genome), but similar in Oryza glumaepatula and Oryza
      meridionalis (AA genome) compared with the cultivated rice (cv. Nipponbare).
      However, all wild rice species and the cultivated rice showed similar
      concentration of Si in the shoots when grown in a field. All species with AA
      genome showed the same amino acid sequence of both Lsi1 and Lsi2 as O. sativa,
      whereas species with EE and BB genome showed several nucleotide differences in
      both Lsi1 and Lsi2. However, proteins encoded by these genes also showed
      transport activity for Si in Xenopus oocyte. The mRNA expression of Lsi1 in all
      wild rice species was lower than that in the cultivated rice, whereas the
      expression of Lsi2 was lower in O. rufipogon and O. barthii but similar in other
      species. Similar cellular localization of Lsi1 and Lsi2 was observed in all wild
      rice as the cultivated rice. These results indicate that superior Si uptake, the
      important trait for rice growth, is basically conserved in wild and cultivated
      rice species. 

PMID- 24320721
TI  - Food companies are not social service agencies.

PMID- 24320722
TI  - Policy and system changes in marketing foods to children.

PMID- 24320723
TI  - Cooking with Kids positively affects fourth graders' vegetable preferences and
      attitudes and self-efficacy for food and cooking.
AB  - BACKGROUND: Cooking with Kids (CWK), an experiential school-based food education
      program, has demonstrated modest influence on fruit and vegetable preference,
      food and cooking attitudes (AT), and self-efficacy (SE) among fourth-grade,
      mostly low-income Hispanic students in a quasiexperimental study with an
      inconsistent baseline. Effect was notably strong for boys and those without
      previous cooking experience. The aim of this project was to assess the effect of
      CWK with a mostly non-Hispanic white sample that assured no previous CWK
      exposure. METHODS: The randomized, controlled assessment of CWK effect on fourth
      graders was conducted with 257 students in 12 classes in four public schools. CWK
      included a 1-hour introductory lesson, three 2-hour cooking classes, and three 1
      hour fruit and vegetable tasting sessions led by trained food educators during
      the school day for one semester. Fruit preference, vegetable preference, and
      cooking AT and SE were assessed with a tested 35-item measure, shown to have test
      retest reliability. Univariate analyses considered gender and previous cooking
      experience. RESULTS: Intervention efficacy was confirmed in this mostly white
      sample (75%; 79% with previous cooking experience; 54% girls). Increases in
      vegetable preference, AT, and SE were all significantly greater in CWK students
      with etap (2) of 0.03, 0.02, and 0.06, respectively. CWK most strongly improved
      AT and SE for boys without previous cooking experience. CONCLUSIONS: CWK
      significantly improved fourth-grade students' vegetable preferences, AT, and SE
      toward food and cooking, which are factors important to healthful eating and
      obesity prevention. Noncookers, especially boys, benefitted from this
      intervention.

PMID- 24320724
TI  - Promoting "healthy" food in the context of internal regulation of eating: comment
      on Slusser et al.

PMID- 24320725
TI  - Enhanced catalysis of oxime-based bioconjugations by substituted anilines.
AB  - The conjugation of biomolecules by chemoselective oxime ligation is of great
      interest for the site-specific modification of proteins, peptides, nucleic acids,
      and carbohydrates. These conjugations proceed optimally at a reaction pH of 4-5,
      but some biomolecules are not soluble or stable under these conditions. Aniline
      can be used as a nucleophilic catalyst to enhance the rate of oxime formation,
      but even in its presence, the reaction rate at neutral pH can be slower than
      desired, particularly at low reagent concentrations and/or temperature. Recently,
      alternative catalysts with improved properties were reported, including
      anthranilic acid derivatives for small molecule ligations, as well as m
      phenylenediamine at high concentrations for protein conjugations. Here, we report
      that p-substituted anilines containing an electron-donating ring substituent are
      superior catalysts of oxime-based conjugations at pH 7. One such catalyst, p
      phenylenediamine, was studied in greater detail. This catalyst was highly
      effective at neutral pH, even at the low concentration of 2 mM. In a model oxime
      ligation using aminooxy-functionalized PEG, catalysis at pH 7 resulted in a 120
      fold faster rate of protein PEGylation as compared to an uncatalyzed reaction,
      and 19-fold faster than the equivalent aniline-catalyzed reaction. p
      Phenylenediamine (10 mM) was also an effective catalyst under acidic conditions
      and was more efficient than aniline throughout the pH range 4-7. This catalyst
      allows efficient oxime bioconjugations to proceed under mild conditions and low
      micromolar concentrations, as demonstrated by the PEGylation of a small protein. 

PMID- 24320726
TI  - A clinical prediction rule to identify patients at heightened risk for early
      demise following cardiac resynchronization therapy.
AB  - BACKGROUND: In patients with advanced heart failure, the decision of whether to
      pursue cardiac resynchronization therapy (CRT) or to proceed directly to advanced
      heart failure therapies can be challenging. We sought to create a prediction rule
      to identify patients with advanced systolic heart failure at heightened risk of
      rapid deterioration despite receiving CRT. METHODS: Clinical data were collected
      on consecutive patients with advanced heart failure presenting for a new CRT
      device at the Cleveland Clinic between February 12, 2002 and July 8, 2008. Early
      demise was defined as death, left ventricular assist device, or heart transplant
      within 6 months following CRT implant. Using a multivariate model, variables
      associated with early demise were identified and a prediction rule created.
      RESULTS: A total of 879 patients were included of whom 47 met criteria for early
      demise. Using forward stepwise regression followed by a bootstrapping analysis,
      the final model included: left ventricular end-diastolic diameter >=6.5 cm (OR
      3.23 [1.72-6.06 g], P < 0.001), the presence of a non-left bundle branch block
      (non-LBBB) morphology (OR 2.18 [1.18-4.04, P = 0.013]), creatinine >=1.5 mg/dL
      (OR 2.98 [1.52-5.49], P < 0.001), and lack of or intolerance to beta-blocker use
      (OR 2.80 [1.46-5.39], P = 0.002). The specificity for >=2 and >=3 risk factors
      was 72.6% and 94.6%, respectively. CONCLUSIONS: Left ventricular dilatation, the
      presence of a non-LBBB morphology, renal dysfunction, and lack of or intolerance
      to beta-blockers are associated with early demise following CRT. In patients with
      at least 3 of these factors, bypassing CRT with early adoption of advanced heart
      failure therapies may be considered given the high specificity for rapid decline.

PMID- 24320728
TI  - Clinical effectiveness and safety of cetirizine versus rupatadine in chronic
      spontaneous urticaria: a randomized, double-blind, 6-week trial.
AB  - BACKGROUND: Urticaria is a distressing condition associated with diverse clinical
      presentations. Chronic spontaneous urticaria (CsU) is characterized by wheals and
      angioedema. Its treatment requires an algorithmic approach to identify the
      optimum medication. OBJECTIVES: Cetirizine is commonly used in the treatment of
      urticaria. Rupatadine is a selective non-sedating H1 -antihistamine approved for
      the treatment of CsU. This trial was conducted to ascertain whether the
      properties of rupatadine offer advantages over cetirizine. METHODS: Seventy
      patients with CsU were enrolled. Parameters assessed included: (i) mean number of
      wheals (MNW); (ii) pruritus; (iii) mean total symptom score (MTSS); (iv) size of
      wheal; (v) interference of wheals with sleep; and (vi) sedation. Patients with
      CsU were divided randomly into two groups. Routine investigations were performed
      at baseline and at the end of the study. RESULTS: Evaluations of MTSS, MNW, and
      pruritus revealed statistically significant differences at week 3 compared with
      baseline in the cetirizine group. However, greater reductions in these parameters
      were obtained with rupatadine. In patients receiving rupatadine, reductions in
      the MNW, size of wheals, and intensity of erythema were also significant at six
      weeks (P < 0.001) and were significantly greater than those in the cetirizine
      group (P < 0.05). CONCLUSIONS: Improvements in MTSS, MNW, size of wheals,
      intensity of erythema, and differential eosinophil count imply that rupatadine is
      a particularly attractive therapeutic modality compared with cetirizine for the
      treatment of CsU.

PMID- 24320727
TI  - Mitochondrial uncoupling protein 2 induces cell cycle arrest and necrotic cell
      death.
AB  - Uncoupling protein 2 (UCP2) is a mitochondrial membrane protein that regulates
      energy metabolism and reactive oxygen species (ROS) production. We generated
      mouse carboxy- and amino-terminal green fluorescent protein (GFP)-tagged UCP2
      constructs to investigate the effect of UCP2 expression on cell proliferation and
      viability. UCP2-transfected Hepa 1-6 cells did not show reduced cellular
      adenosine triphosphate (ATP) but showed increased levels of glutathione. Flow
      cytometry analysis indicated that transfected cells were less proliferative than
      nontransfected controls, with most cells blocked at the G1 phase. The effect of
      UCP2 on cell cycle arrest could not be reversed by providing exogenous ATP or
      oxidant supply, and was not affected by the chemical uncoupler carbonyl cyanide-p
      trifluoromethoxyphenylhydrazone (FCCP). However, this effect of UCP2 was
      augmented by treatment with genistein, a tyrosine kinase inhibitor, which by
      itself did not affect cell proliferation on control hepatocytes. Western blotting
      analysis revealed decreased expression levels of CDK6 but not CDK2 and D-type
      cyclins. Examination of cell viability in UCP2-transfected cells with Trypan Blue
      and Annexin-V staining revealed that UCP2 transfection led to significantly
      increased cell death. However, characteristics of apoptosis were absent in UCP2
      transfected Hepa 1-6 cells, including lack of oligonucleosomal fragmentation
      (laddering) of chromosomal DNA, release of cytochrome c from mitochondria, and
      cleavage of caspase-3. In conclusion, our results indicate that UCP2 induces cell
      cycle arrest at G1 phase and causes nonapoptotic cell death, suggesting that UCP2
      may act as a powerful influence on hepatic regeneration and cell death in the
      steatotic liver.

PMID- 24320729
TI  - Assessment of the activity of photocatalytic paint using a simple smart ink
      designed for high activity surfaces.
AB  - The use of an acid violet 7 (AV7) smart ink to assess the activity of
      photocatalytic paint is demonstrated. A linear correlation is established between
      the change in oxidized dye concentration, as measured by diffuse reflectance, and
      the change in the green component of the RGB color values, obtained using a
      portable hand-held scanner, suggesting that such tests can be monitored easily
      using an inexpensive piece of hand-held office equipment, as opposed to an
      expensive lab-based instrument, such as a diffuse reflectance UV/vis
      spectrophotometer. The bleaching of the AV7 follows first order kinetics, at a
      rate that is linearly dependent upon the UVA irradiance (0.30-3.26 mW cm(-2)). A
      comparison of relative rate of bleaching of the AV7 ink with the relative rate of
      removal of NOx, as determined using the ISO test (ISO 22197-1:2007), established
      a linear relationship between the two sets of results and the relevance of this
      correlation is discussed briefly. 

PMID- 24320732
TI  - New approach to Tolman's electronic parameter based on local vibrational modes.
AB  - Tolman's electronic parameter (TEP) derived from the A1-symmetrical CO stretching
      frequency of nickel-phosphine-tricarbonyl complexes, R3PNi(CO)3, is brought to a
      new, improved level by replacing normal with local vibrational frequencies. CO
      normal vibrational frequencies are always flawed by mode-mode coupling especially
      with metal-carbon stretching modes, which leads to coupling frequencies as large
      as 100 cm(-1) and can become even larger when the transition metal and the number
      of ligands is changed. Local TEP (LTEP) values, being based on local CO
      stretching force constants rather than normal mode frequencies, no longer suffer
      from mode coupling and mass effects. For 42 nickel complexes of the type
      LNi(CO)3, it is shown that LTEP values provide a different ordering of ligand
      electronic effects as previously suggested by TEP and CEP values. The general
      applicability of the LTEP concept is demonstrated. 

PMID- 24320731
TI  - Cytoplasmic genome substitution in wheat affects the nuclear-cytoplasmic cross
      talk leading to transcript and metabolite alterations.
AB  - BACKGROUND: Alloplasmic lines provide a unique tool to study nuclear-cytoplasmic
      interactions. Three alloplasmic lines, with nuclear genomes from Triticum
      aestivum and harboring cytoplasm from Aegilops uniaristata, Aegilops tauschii and
      Hordeum chilense, were investigated by transcript and metabolite profiling to
      identify the effects of cytoplasmic substitution on nuclear-cytoplasmic signaling
      mechanisms. RESULTS: In combining the wheat nuclear genome with a cytoplasm of H.
      chilense, 540 genes were significantly altered, whereas 11 and 28 genes were
      significantly changed in the alloplasmic lines carrying the cytoplasm of Ae.
      uniaristata or Ae. tauschii, respectively. We identified the RNA maturation
      related process as one of the most sensitive to a perturbation of the nuclear
      cytoplasmic interaction. Several key components of the ROS chloroplast retrograde
      signaling, together with the up-regulation of the ROS scavenging system, showed
      that changes in the chloroplast genome have a direct impact on nuclear
      cytoplasmic cross-talk. Remarkably, the H. chilense alloplasmic line down
      regulated some genes involved in the determination of cytoplasmic male sterility
      without expressing the male sterility phenotype. Metabolic profiling showed a
      comparable response of the central metabolism of the alloplasmic and euplasmic
      lines to light, while exposing larger metabolite alterations in the H. chilense
      alloplasmic line as compared with the Aegilops lines, in agreement with the
      transcriptomic data. Several stress-related metabolites, remarkably raffinose,
      were altered in content in the H. chilense alloplasmic line when exposed to high
      light, while amino acids, as well as organic acids were significantly decreased.
      Alterations in the levels of transcript, related to raffinose, and the
      photorespiration-related metabolisms were associated with changes in the level of
      related metabolites. CONCLUSION: The replacement of a wheat cytoplasm with the
      cytoplasm of a related species affects the nuclear-cytoplasmic cross-talk leading
      to transcript and metabolite alterations. The extent of these modifications was
      limited in the alloplasmic lines with Aegilops cytoplasm, and more evident in the
      alloplasmic line with H. chilense cytoplasm. We consider that, this finding might
      be linked to the phylogenetic distance of the genomes.

PMID- 24320733
TI  - The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin
      do not impair innate and adaptive immune responses.
AB  - Inhibitors of dipeptidylpeptidase IV (DPP-IV) represent a novel class of
      frequently used anti-diabetic drugs. In addition to its function in metabolic
      regulation, DPP-IV also plays a role in the immune system. Whether the DPP-IV
      inhibitors sitagliptin, vildagliptin or saxagliptin impair immune responses is,
      however, currently unknown. Here, we investigated the effect of these agents on
      both innate and adaptive immunity. We found that the DPP-IV inhibitors did not
      affect the innate immune response induced by Toll-like receptor (TLR) ligands, as
      cytokine secretion and induction of co-stimulatory molecules by human blood
      mononuclear cells was not impaired. Furthermore, proliferation of T cells and
      suppressive function of regulatory T cells was preserved. Mice treated with
      vildagliptin showed normal cytokine production, immune cell activation and
      lymphocyte trafficking upon TLR activation. Thus, crucial immunological
      parameters remain unaffected upon treatment with DPP-IV inhibitors, a fact that
      is reassuring with respect to safety of these drugs. 

PMID- 24320734
TI  - Dyschromatosis universalis hereditaria: a case report.

PMID- 24320735
TI  - Criterion and convergent validity of the Montreal cognitive assessment with
      screening and standardized neuropsychological testing.
AB  - OBJECTIVES: To compare the validity of the Montreal Cognitive Assessment (MoCA)
      with the criterion standard of standardized neuropsychological testing and to
      compare the convergent validity of the MoCA with that of existing screening tools
      and global measures of cognition. DESIGN: Cross-sectional observational study.
      SETTING: Tertiary care hospital-based cognitive neurology subspecialty clinic.
      PARTICIPANTS: A convenience sample of 107 individuals with mild Alzheimer's
      disease (AD, n=75) or mild cognitive impairment (MCI, n=32) from the Sunnybrook
      Dementia Study. MEASUREMENTS: In addition to the MoCA, all participants completed
      the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale (DRS),
      and detailed neuropsychological testing. RESULTS: Convergent validity was
      supported, with MoCA scores correlating well with the MMSE (correlation
      coefficient (r)=0.66, P<.001) and the DRS (r=0.77, P<.001) and the MoCA better
      associated with the DRS than did the MMSE. Criterion validity was supported, with
      MoCA subscores according to cognitive domain correlating well with analogous
      neuropsychological tests and, in the case of memory (area under the receiver
      operating characteristic curve (AUC)=0.86), executive (AUC=0.79), and
      visuospatial function (AUC=0.79), being reasonably sensitive to impairment in
      those domains. CONCLUSION: The MoCA is a valid assessment of cognition that shows
      good agreement with existing screening tools and global measures (convergent
      validity) and was superior to the MMSE in this regard. The MoCA domain-specific
      subscores align with performance on more-detailed neuropsychological tests,
      suggesting not only good criterion validity for the MoCA, but also that it may be
      useful in guiding further neuropsychological testing.

PMID- 24320736
TI  - Role of single nucleotide polymorphisms in estrogen-metabolizing enzymes and
      susceptibility to uterine leiomyoma in Han Chinese: a case-control study.
AB  - AIM: To explore the relationship between estrogen metabolism enzyme gene
      polymorphism and susceptibility to uterine fibroids, and to seek the screening
      molecular markers for genetic traits in uterine fibroid populations. METHODS: A
      total of 300 female Han Chinese patients and 300 healthy female Han Chinese
      volunteers in Nanjing (age range, 30-50 years) were recruited from Zhongda
      Hospital, Southeast University from February 2011 to March 2012. The single
      nucleotide polymorphisms (SNP) of estrogen-metabolizing enzyme genes from the two
      groups of women were examined by polymerase chain reaction denaturing high
      performance liquid chromatography, which were four COMT gene loci including
      rs3087869, rs165774, rs165599 and rs4680, three CYP1A1 gene loci including
      rs1048943, rs4646421 and rs4646422, and three CYP1B1 gene loci including
      rs1056827, rs1056836 and rs1056837. Genotype frequencies among cases and controls
      were calculated and analyzed by binary logistic regression. RESULTS: Regression
      analysis of SNP showed that COMT IVS1+2329C>T (odds ratio [OR], 2.872; 95% CI,
      1.690-4.882) and Val158Met (OR, 2.593; 95% CI, 1.546-4.350), CYP1A1 Ile462Val
      (OR, 2.383; 95% CI, 1.418-4.005) and Gly45Asp (OR, 2.489; 95% CI, 1.49-4.159),
      and CYP1B1 Ala119Ser (OR, 3.361; 95% CI, 2.035-5.552) and Leu432Val (OR, 0.164;
      95% CI, 0.061-0.441) influenced uterine fibroids significantly (P < 0.05). Allele
      and genotype frequencies among cases and control were calculated and examined to
      match the Hardy-Weinberg equilibrium with the chi2-test. CONCLUSION: The genetic
      polymorphisms of IVS1+2329C>T and Val158Met loci in COMT, Ile462Val and Gly45Asp
      loci in CYP1A1 and Ala119Ser loci in CYP1B1 were risk factors for uterine
      leiomyoma development, and Leu432Val locus in CYB1B1 may be a protective factor.
      The results provide a theoretical basis for genetic screening and early
      intervention for uterine leiomyoma-susceptible populations.

PMID- 24320737
TI  - Overlimiting current and shock electrodialysis in porous media.
AB  - Most electrochemical processes, such as electrodialysis, are limited by
      diffusion, but in porous media, surface conduction and electroosmotic flow also
      contribute to ionic flux. In this article, we report experimental evidence for
      surface-driven overlimiting current (faster than diffusion) and deionization
      shocks (propagating salt removal) in a porous medium. The apparatus consists of a
      silica glass frit (1 mm thick with a 500 nm mean pore size) in an aqueous
      electrolyte (CuSO4 or AgNO3) passing ionic current from a reservoir to a cation
      selective membrane (Nafion). The current-voltage relation of the whole system is
      consistent with a proposed theory based on the electroosmotic flow mechanism over
      a broad range of reservoir salt concentrations (0.1 mM to 1.0 M) after accounting
      for (Cu) electrode polarization and pH-regulated silica charge. Above the
      limiting current, deionized water (~10 MUM) can be continuously extracted from
      the frit, which implies the existence of a stable shock propagating against the
      flow, bordering a depleted region that extends more than 0.5 mm across the
      outlet. The results suggest the feasibility of shock electrodialysis as a new
      approach to water desalination and other electrochemical separations. 

PMID- 24320738
TI  - An examination of comorbid asthma and obesity: assessing differences in physical
      activity, sleep duration, health-related quality of life and parental distress.
AB  - OBJECTIVE: Compare youth with comorbid asthma and obesity to youth with obesity
      only to determine if differences exist in body mass index, dietary intake, levels
      of physical activity, sleep duration and health-related quality of life. Levels
      of parent distress were also compared. METHODS: Participants included 248
      children (n = 175 in Obesity group; n = 73 in Asthma + Obesity group) with a BMI
      >= 85th percentile for age and gender, and their participating parent(s) or legal
      guardian(s). Measures of child height and weight were obtained by study personnel
      and Z-scores for child body mass index were calculated using age- and gender
      specific norms. Child physical activity and sleep duration were measured via
      accelerometers. Dietary intake, health-related quality of life and parent
      distress were assessed via self-report. RESULTS: The Asthma + Obesity group
      evidenced significantly higher body mass index scores, and had lower sleep
      duration. There was a non-statistically significant trend for lower levels of
      physical activity among children in the Asthma + Obesity group. Dietary intake,
      health-related quality of life and parent distress did not differ between groups.
      CONCLUSIONS: Youth with comorbid asthma and obesity are at increased risk for
      negative health and psychosocial difficulties compared to youth who are
      overweight or obese only. Professionals providing treatment for youth with asthma
      are encouraged to assess the implications of weight status on health behaviors
      and family psychosocial adjustment.

PMID- 24320739
TI  - Quality of care factors associated with unplanned readmissions of older medical
      patients: a case-control study.
AB  - BACKGROUND: Unplanned readmissions befall up to 25% of acutely hospitalised older
      patients, and many may be potentially preventable. AIM: To assess the type and
      prevalence of quality of care factors associated with potentially preventable
      readmissions to a tertiary hospital general medicine service. METHODS: A
      retrospective case-control study was undertaken of hospital records of patients
      65 years or older admitted acutely between 1 January 2005 and 31 December 2010.
      Readmissions up to 30 days postdischarge (cases) were purposively sampled
      according to frequencies of primary discharge diagnoses coded during the study
      period. Non-readmitted patients (controls), matched according to age, sex and
      primary discharge diagnosis on index admission, were selected in a 1.7:1 ratio.
      RESULTS: One hundred and thirteen cases and 198 controls were analysed, the
      former demonstrating a significantly higher comorbidity burden (mean (+/-standard
      deviation) comorbidity score 6.6 (+/-2.2) vs 5.6 (+/-2.4), P = 0.003) and a
      higher proportion of individuals with one or more hospitalisations over the
      preceding 6 months (55.7% vs 8.1%, P < 0.001). Among readmitted patients, 50
      (44.3%) were associated with one or more quality factors versus 23 (11.6%)
      controls (P < 0.001). The most common were: failure to develop/activate an
      advance care plan (18, 15.9% vs 2, 1.0%; P < 0.001); suboptimal management of
      presenting illness (13, 11.4% vs 0, 0%; P < 0.001); inadequate assessment of
      functional limitations (11, 9.7% vs 0, 0%; P < 0.001); and potentially
      preventable complication of therapy (8, 7.1% vs 1, 0.5%, P = 0.002). CONCLUSIONS:
      Quality of care factors are more common among readmitted than among non
      readmitted older patients suggesting potential for remedial strategies. Such
      strategies may still have limited effects as older, frail patients with advanced
      diseases and multimorbidity will likely retain a high propensity for readmission
      despite optimal care.

PMID- 24320741
TI  - Procedure for microbial identification based on Matrix-Assisted Laser
      Desorption/Ionization-Time of Flight Mass Spectrometry from screening-positive
      urine samples.
AB  - Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry is a
      widely used proteomic technique in clinical microbiology laboratories, and
      enables microbial identification directly from clinical samples. This study seeks
      to establish a protocol for bacterial identification from monomicrobial urine
      samples that have tested positive in the screening with Sysmex UF-1000i (Sysmex
      Corporation, Kobe, Japan). Sysmex UF-1000i counts >=1 * 10(7) bacteria/mL
      indicate a sufficient bacterial concentration to allow direct identification from
      urine, with 87.5% sensitivity. Microbial identification from urine with Sysmex UF
      1000i counts between 1 * 10(5) and 1 * 10(7) bacteria/ml requires preincubation
      to obtain the adequate amount of bacteria needed for analysis, and 91.7%
      sensitivity thus being achieved. 

PMID- 24320740
TI  - Versatile photocatalytic systems for H2 generation in water based on an efficient
      DuBois-type nickel catalyst.
AB  - The generation of renewable H2 through an efficient photochemical route requires
      photoinduced electron transfer (ET) from a light harvester to an efficient
      electrocatalyst in water. Here, we report on a molecular H2 evolution catalyst
      (NiP) with a DuBois-type [Ni(P2(R')N2(R"))2](2+) core (P2(R')N2(R") = bis(1,5-R'
      diphospha-3,7-R"-diazacyclooctane), which contains an outer coordination sphere
      with phosphonic acid groups. The latter functionality allows for good solubility
      in water and immobilization on metal oxide semiconductors. Electrochemical
      studies confirm that NiP is a highly active electrocatalyst in aqueous
      electrolyte solution (overpotential of approximately 200 mV at pH 4.5 with a
      Faradaic yield of 85 +/- 4%). Photocatalytic experiments and investigations on
      the ET kinetics were carried out in combination with a phosphonated Ru(II)
      tris(bipyridine) dye (RuP) in homogeneous and heterogeneous environments. Time
      resolved luminescence and transient absorption spectroscopy studies confirmed
      that directed ET from RuP to NiP occurs efficiently in all systems on the nano-
      to microsecond time scale, through three distinct routes: reductive quenching of
      RuP in solution or on the surface of ZrO2 ("on particle" system) or oxidative
      quenching of RuP when the compounds were immobilized on TiO2 ("through particle"
      system). Our studies show that NiP can be used in a purely aqueous solution and
      on a semiconductor surface with a high degree of versatility. A high TOF of 460
      +/- 60 h(-1) with a TON of 723 +/- 171 for photocatalytic H2 generation with a
      molecular Ni catalyst in water and a photon-to-H2 quantum yield of approximately
      10% were achieved for the homogeneous system.

PMID- 24320742
TI  - Hematopoietic stem cells: do they have a role in keloid pathogenesis?
AB  - Keloids are slow growing neoplasms characterized by benign proliferation of
      fibroblasts that is due, at least in part, to altered cytokine profiles. Stem
      cells were claimed to play a role in skin tumor development. However, their role
      in keloid formation is unclear. The current study investigated the
      immunoreactivity of CD34 and c-KIT antibodies in 30 cases with keloid lesions
      together with normal skin biopsies of 30, sex and age-matched subjects
      representing the control group. Examined keloid sections showed positive dermal
      stromal immunoreactivity for CD34 in 76.7% of cases. CD34 expression intensity
      and H score were upregulated in keloid tissue relative to normal skin (p <
      0.0001, p = 0.0002, respectively) and in perilesional relative to lesional tissue
      (p = 0.03, p < 0.001, respectively). c-KIT showed positive dermal stromal
      expression in all cases. Dermal c-KIT expression intensity and H score were
      upregulated in keloid tissue relative to normal skin (p < 0.008, p < 0.001,
      respectively) and in perilesional relative to lesional tissue (p < 0.0001, p <
      0.001, respectively). Lesional skin showed more staining of basal keratinocytes
      when compared to perilesional tissue (p < 0.0001). Hematopoietic stem cells may
      share in keloid pathogenesis. Further studies are warranted to gain firmer
      conclusion about the exact role played by these cells and the significance of
      their perilesional accumulation. The future therapy of keloid scars may have to
      target this stem cell population in order to deprive these tumors of their
      regenerative cell pools.

PMID- 24320743
TI  - Down syndrome and neurofibromatosis: a case report.
AB  - BACKGROUND: The dental management of a patient presenting with both Down syndrome
      and neurofibromatosis type 1 (NF1) has not previously been described well in the
      dental literature. CASE DESCRIPTION: A 20-year-old male with both of these
      genetic anomalies sought comprehensive treatment at the Special Needs Dental
      clinic at the Arizona School of Dentistry and Oral Health. He presented with
      multiple decayed surfaces, retained primary teeth, and intra/extra oral soft
      tissue tumors. Dental extractions and tumor reduction surgery took place at a
      private dental office due to the need for intravenous sedation for patient
      management. At the conclusion of the patient's -treatment, while his oral health
      was improved, there was little improvement in the facial aesthetics of his case.
      CLINICAL IMPLICATIONS: Coordinating care among health care providers in a patient
      with Trisomy 21 and NF1 is essential for a reliable and predictable outcome.
      However, as neurofibromas are often known to recur, the treatment risks and
      advantages should be reviewed prior to surgical intervention.

PMID- 24320744
TI  - Magnetic resonance imaging findings associated with lateral cerebral
      ventriculomegaly in English Bulldogs.
AB  - Multiple congenital or developmental anomalies associated with the central
      nervous system have been reported in English Bulldogs. The purpose of this
      retrospective study was to identify and describe the prevalence and MRI
      characteristics of these anomalies and their association with presence and degree
      of cerebral ventriculomegaly. Magnetic resonance imaging studies of 50 English
      Bulldogs were evaluated. Forty-eight dogs had some degree of cerebral
      ventriculomegaly, 27 of which had an otherwise normal brain. Presence of lateral
      ventriculomegaly was not significantly associated with presence of another
      intracranial lesion. Appearance of the septum pellucidum was variable, ranging
      from intact to incomplete or completely absent. The corpus callosum was
      subjectively thinned in all but three dogs, two of which had normal lateral
      ventricles. Fusion of the rostral colliculi was not found in any dog. A
      persistent craniopharyngeal canal was identified in one dog. Aqueductal stenosis
      caused by fusion of the rostral colliculi was not identified in any dog. Findings
      indicated that cerebral ventriculomegaly is a common finding in English Bulldogs
      with or without other intracranial lesions, aqueductal stenosis caused by fusion
      of the rostral colliculi is unlikely to be a common etiology leading to
      obstructive hydrocephalus, and a large craniopharyngeal canal is a rare finding
      that has unknown clinical significance at this time.

PMID- 24320745
TI  - Transcranial direct current stimulation in de novo artistic ability after stroke.

PMID- 24320746
TI  - Differential effects of ocean acidification on carbon acquisition in two bloom
      forming dinoflagellate species.
AB  - Dinoflagellates represent a cosmopolitan group of phytoplankton with the ability
      to form harmful algal blooms. Featuring a Ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RubisCO) with very low CO2 affinities, photosynthesis of
      this group may be particularly prone to carbon limitation and thus benefit from
      rising atmospheric CO2 partial pressure (pCO2) under ocean acidification (OA).
      Here, we investigated the consequences of OA on two bloom-forming dinoflagellate
      species, the calcareous Scrippsiella trochoidea and the toxic Alexandrium
      tamarense. Using dilute batch incubations, we assessed growth characteristics
      over a range of pCO2 (i.e. 180-1200 uatm). To understand the underlying
      physiology, several aspects of inorganic carbon acquisition were investigated by
      membrane-inlet mass spectrometry. Our results show that both species kept growth
      rates constant over the tested pCO2 range, but we observed a number of species
      specific responses. For instance, biomass production and cell size decreased in
      S. trochoidea, while A. tamarense was not responsive to OA in these measures. In
      terms of oxygen fluxes, rates of photosynthesis and respiration remained
      unaltered in S. trochoidea whereas respiration increased in A. tamarense under
      OA. Both species featured efficient carbon concentrating mechanisms (CCMs) with a
      CO2-dependent contribution of HCO3(-) uptake. In S. trochoidea, the CCM was
      further facilitated by exceptionally high and CO2-independent carbonic anhydrase
      activity. Comparing both species, a general trade-off between maximum rates of
      photosynthesis and respective affinities is indicated. In conclusion, our results
      demonstrate effective CCMs in both species, yet very different strategies to
      adjust their carbon acquisition. This regulation in CCMs enables both species to
      maintain growth over a wide range of ecologically relevant pCO2 .

PMID- 24320747
TI  - A comparison of incidence and risk factors for serious adverse events in
      rheumatoid arthritis patients with etanercept or adalimumab in Korea and Japan.
AB  - OBJECTIVE: To compare the incidence and risk factors of serious adverse events
      (SAEs) in rheumatoid arthritis (RA) patients treated with etanercept (ETN) or
      adalimumab (ADA) between Korean and Japanese registries. METHODS: We recruited
      416 RA patients [505.2 patient-years (PYs)] who started ETN or ADA from Korean
      registry and 537 RA patients (762.0 PY) from Japanese registry. The patient
      background, incidence rate (IR) of SAE in 2 years, and risk factors for SAEs were
      compared. RESULTS: Korean patients were younger and used more nonbiologic DMARDs,
      higher doses of methotrexate, and lower doses of prednisolone (PSL). The IR of
      SAEs (/100 PY) was higher in the Japanese registry compared to the Korean [13.65
      vs. 6.73]. In both registries, infection was the most frequently reported SAE.
      The only significant risk factor for SAEs in Korean registry was age by decade
      [1.45]. In Japanese registry, age by decade [1.54], previous use of nonbiologic
      DMARDs >= 4 [1.93], and concomitant use of oral PSL >= 5 mg/day [2.20] were
      identified as risk factors for SAEs. CONCLUSIONS: The IR of SAE in Japan,
      especially infection, was higher than that of Korea, which was attributed to the
      difference of demographic and clinical characteristics of RA patients and
      treatment profiles.

PMID- 24320748
TI  - Modulation of cell wall synthesis and susceptibility to vancomycin by the two
      component system AirSR in Staphylococcus aureus NCTC8325.
AB  - BACKGROUND: Vancomycin has been the medication of last resort to cure infections
      caused by Staphylococcus aureus since the increase in the prevalence of
      methicillin-resistant Staphylococcus aureus (MRSA). Some strains have developed
      vancomycin-intermediate resistance, which is generally associated with altered
      expression of or mutations in some part of the two-component system (TCS), such
      as GraSR, VraSR, and WalKR. RESULTS: We deleted the AirSR TCS in S. aureus
      NCTC8325 and compared the resultant transcript levels with those of its parent
      strain using microarray analysis. The results indicated that more than 20 genes
      that are related to cell wall metabolism were down-regulated in the airSR mutant.
      The airSR mutant exhibited reduced autolysis rates and reduced viability in the
      presence of vancomycin. Real-time reverse transcription PCR and DNA mobility
      shift assays verified that AirR can directly bind to and regulate genes that
      function in cell wall metabolism (cap, pbp1, and ddl) and autolysis (lytM).
      CONCLUSIONS: AirSR acts as a positive regulator in cell wall biosynthesis and
      turnover in Staphylococcus aureus NCTC8325.

PMID- 24320749
TI  - Mechanistic characterization of a 2-thioxanthine myeloperoxidase inhibitor and
      selectivity assessment utilizing click chemistry--activity-based protein
      profiling.
AB  - Myeloperoxidase (MPO) is a heme peroxidase that catalyzes the production of
      hypochlorous acid. Despite a high level of interest in MPO as a therapeutic
      target, there have been limited reports about MPO inhibitors that are suitable
      for evaluating MPO in pharmacological studies. 2-Thioxanthine, 3-(2-ethoxypropyl)
      2-thioxo-2,3-dihydro-1H-purin-6(9H)-one (A), has recently been reported to
      inhibit MPO by covalently modifying the heme prosthetic group. Here we report a
      detailed mechanistic characterization demonstrating that A possesses all the
      distinguishing features of a mechanism-based inactivator. A is a time-dependent
      MPO inhibitor and displays saturable inactivation kinetics consistent with a two
      step mechanism of inactivation and a potency (k(inact)/K(I) ratio) of 8450 +/-
      780 M-1 s-1. MPO inactivation by A is dependent on MPO catalysis and is protected
      by substrate. A reduces MPO compound I to compound II with a second-order rate
      constant of (0.801 +/- 0.056) * 106 M-1 s-1, and its irreversible inactivation of
      MPO occurs prior to release of the activated inhibitory species. Despite its
      relatively high selectivity against a broad panel of more than 100 individual
      targets, including enzymes, receptors, transporters, and ion channels, we
      demonstrate that A labels multiple other protein targets in the presence of MPO.
      By synthesizing an alkyne analogue of A and utilizing click chemistry-activity
      based protein profiling, we present that the MPO-activated inhibitory species can
      diffuse away to covalently modify other proteins, as reflected by the relatively
      high partition ratio of A, which we determined to be 15.6. This study highlights
      critical methods that can guide the discovery and development of next-generation
      MPO inhibitors.

PMID- 24320750
TI  - Clinical utility of a biopsy-based cell cycle gene expression assay in localized
      prostate cancer.
AB  - OBJECTIVE: The CCP signature test (Prolaris) quantifies a patient's risk of
      disease progression and prostate cancer specific mortality using a gene
      expression-based cell cycle progression (CCP) score. This study evaluated the
      potential clinical utility of the CCP test in a US-based clinical setting.
      METHODS: Urologists who participated in a prospective clinical study were sent a
      retrospective questionnaire to assess the value of the CCP test result. Fifteen
      board-certified urologists participated in the study, representing 15 distinct
      community urology group practices. Questionnaires were received for 294 evaluable
      patients. All patients had localized prostate cancer (T1-T3b, N0, M0). RESULTS:
      Physicians found the CCP score valuable and indicated that 55% of tests generated
      a mortality risk that was either higher or lower than expected. Physicians also
      indicated that 32% of test results would lead to a definite or possible change in
      treatment. The data suggest that the test would have the net effect of shifting
      patients from more aggressive treatment to more conservative treatment. This was
      evidenced by the significant association between change in treatment and lower
      CCP scores (p < 0.002) and by the fact that 62% of tests likely to lead to a
      definite or possible change in treatment had mortality risks lower than the
      physician expected versus only 10% with risks higher than expected. STUDY
      LIMITATIONS: This study measured the retrospectively assessed likelihood of
      change in treatment as estimated by the physician, not the actual change in
      treatment. CONCLUSIONS: The CCP score adds meaningful new information to risk
      assessment for localized prostate cancer patients. Real-world use of the test is
      likely to lead to a change in treatment in a significant portion of tested
      patients, particularly by shifting patients towards more conservative management.
      This could reduce overtreatment of patients with less aggressive disease,
      decreasing patient morbidity and costs for payers and the healthcare system.

PMID- 24320751
TI  - Hyperbaric oxygen treatment of tissue-engineered mucosa enhances secretion of
      angiogenic factors in vitro.
AB  - The survival of tissue-engineered mucosa (TEM) after implantation is mostly
      dependent on the presence of blood vessels for continuous oxygen supply.
      Therefore the stimulation of vascularization of TEM is essential to improve
      survival in vivo. Hyperbaric oxygen (HBO) treatment, used to improve wound
      healing, stimulates the secretion of angiogenic factors. In this study we
      evaluated the effect of daily HBO treatments on TEM for 1, 3, or 5 consecutive
      days. Overall histology with hematoxylin-eosin staining showed no apparent
      changes after one treatment. After three and five HBO treatments, the basal layer
      became irregular and pyknotic cells were observed. Measurements of the viable
      epithelium showed significant thinning after one and five treatments, however,
      proliferation was not affected. The angiogenic factors keratinocyte growth factor
      (KGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGFbasic),
      and placental growth factor (PlGF) were significantly increased after one HBO
      treatment, whereas after three treatments a significant decrease of FGFbasic and
      PlGF was seen. After five treatments KGF, PlGF, and vascular endothelial growth
      factor (VEGF) were significantly increased. One HBO treatment of TEM enhances the
      secretion of important angiogenic factors, hereby potentially improving the
      survival rate after in vivo implantation. 

PMID- 24320752
TI  - Enhanced field emission from reduced graphene oxide polymer composites.
AB  - Results on electron field emission (FE) from reduced graphene oxide (rGO):poly(3
      hexylthiophene) (P3HT) composite layers are presented. Three different FE
      cathodes were tested and compared: rGO layers on (a) n(+)-Si, (b) composite films
      with different rGO:P3HT ratios, (c) rGO layers on composite films with different
      rGO:P3HT ratios. Experiments show that there is a critical rGO:P3HT ratio in
      which the field-emission performance is remarkably improved. Notably, such
      performance is always superior to that of the optimum rGO/n(+)-Si cathode. On the
      contrary, it is inferior to that attained upon deposition of a second rGO layer
      on top of the rGO:P3HT composite showed the best FE performance that showed turn
      on field of as low as ~0.9 V/MUm and field enhancement factor of ~1900. The
      contributions of the composite film morphology as well as the role of rGO sheet
      substrate interaction on the emission performance are evaluated and discussed.

PMID- 24320753
TI  - Association between IL16 gene polymorphisms and susceptibility to alopecia areata
      in the Korean population.
AB  - BACKGROUND: Alopecia areata (AA) is a chronic disease that presents as non
      scarring hair loss. It is thought to be an organ-specific autoimmune disease
      characterized by T cell infiltrates and cytokine production around anagen-stage
      hair follicles. Interleukin-16 (IL-16) is a T cell-specific chemoattractant known
      to be associated with autoimmune disease. OBJECTIVES: This study was conducted to
      determine whether variation in the IL16 gene contributes to risk for AA in the
      Korean population. METHODS: A total of 270 control subjects and 229 AA patients
      were enrolled. Genomic DNA was prepared from peripheral blood. Four single
      nucleotide polymorphisms (SNPs) (rs17875486 [promoter], rs17875491 [promoter],
      rs11073001 [exon], rs1803275 [exon]) of the IL16 gene were selected. Genotypes
      were determined by direct sequencing. Sequence data were analyzed. Multiple
      logistic regression models were calculated. RESULTS: A significant difference
      emerged between the AA group and the control group for one SNP (rs17875491) of
      IL16. A further significant difference was found between patients with and
      without a family history of AA for a second SNP (rs11073001). CONCLUSIONS: The
      present study found significant differences pertaining to two SNPs of the IL16
      gene between, respectively, AA patients and controls (rs17875491) and AA patients
      with and without a family history of AA (rs11073001). Thus, IL16 polymorphisms
      may play a role in the pathophysiology of AA or in the expression of AA
      phenotypes. Further studies are required to elucidate the role of IL-16 in the
      pathogenesis and clinical manifestation of AA.

PMID- 24320754
TI  - Predictive value of diffusion-weighted magnetic resonance imaging during
      chemoradiotherapy for uterine cervical cancer.
AB  - AIM: The purpose of this study was to evaluate the efficacy of diffusion-weighted
      (DW) magnetic resonance (MR) imaging to predict the tumor response to
      chemoradiotherapy (CRT) of uterine cervical cancer. METHODS: Twenty-five
      consecutive patients with pathologically confirmed uterine cervical cancer
      underwent 1.5-T MR imaging including DW imaging before and during CRT. MR images
      were reviewed for the size and apparent diffusion coefficient (ADC). Pathological
      evaluation of the therapeutic effect was performed 3 months after finishing CRT,
      and we divided the subjects into two groups: complete remission (CR) (n=16) and
      residual tumor (n=9). RESULTS: ADC was lower before CRT than during CRT (0.89 +/-
      0.12 and 1.25 +/- 0.22 * 10-3 mm2/s, respectively) (P<0.01). ADC change between
      before and during CRT (DeltaADC) showed a moderate positive correlation (r=0.435,
      P<0.05) with the tumor regression rates. DeltaADC was higher in the CR group than
      in the residual tumor group (0.43 +/- 0.23 and 0.25 +/- 0.15 * 10-3 mm2/s,
      respectively) (P<0.05). The CR rates were higher in the high DeltaADC group
      (DeltaADC  >= 0.50) than in the low DeltaADC group (DeltaADC <0.49) (100% and
      53%, respectively) but marginally significant (P=0.057). The local control rates
      were not statistically different between high and low DeltaADC groups (83.3% and
      73.7%, respectively) (P=0.602). CONCLUSION: DW imaging including ADC measurement
      may be useful for prediction and early assessment of pathological response to CRT
      for uterine cervical cancer, but its impact on local disease-free survival was
      limited.

PMID- 24320755
TI  - Crystal-chemistry guidelines for noncentrosymmetric A2BO4 Ruddlesden-Popper
      oxides.
AB  - Noncentrosymmetric (NCS) phases are seldom seen in layered A2BO4 Ruddlesden
      Popper (214 RP) oxides. In this work, we uncover the underlying crystallographic
      symmetry restrictions that enforce the spatial parity operation of inversion and
      then subsequently show how to lift them to achieve NCS structures. Simple
      octahedral distortions alone, while impacting the electronic and magnetic
      properties, are insufficient. We show using group theory that the condensation of
      two distortion modes, which describe suitable symmetry unique octahedral
      distortions or a combination of a single octahedral distortion with a
      "compositional" A or B cation ordering mode, is able to transform the
      centrosymmetric aristotype into a NCS structure. With these symmetry guidelines,
      we formulate a data-driven model founded on Bayesian inference that allows us to
      rationally search for combinations of A- and B-site elements satisfying the
      inversion symmetry lifting criterion. We describe the general methodology and
      apply it to 214 iridates with A(2+) cations, identifying RP-structured Ca2IrO4 as
      a potential NCS oxide, which we evaluate with density functional theory. We find
      a strong energetic competition between two closely related polar and nonpolar low
      energy crystal structures in Ca2IrO4 and suggest pathways to stabilize the NCS
      structure. 

PMID- 24320756
TI  - Deposition of non-spherical particles in bifurcating airways.
AB  - Particle morphology plays an important role in pulmonary drug delivery. Not only
      does particle shape affect how particles flow and deposit, the shape also
      influences the drug release rate from the particles. In this work, a semi
      theoretical relationship is developed to describe deposition efficiency as a
      function of fluid and particle properties, incorporating the effect of particle
      shape. For the 10 different particle types studied (with aerodynamic diameters
      between 1 and 10 um), three key deposition mechanisms are identified. All
      particles deposit through inertial impaction, and additionally deposit via
      sedimentation or diffusion, depending on the particle specific momentum.

PMID- 24320757
TI  - Preparation and properties of a pH sensitive carrier based on three kinds of
      polymer blend to control the release of 5-amino salicylic acid.
AB  - CONTEXT: High concentration of 5-amino salicylic acid (5-ASA) in the distal ileum
      and colon is necessary for the treatment of inflammatory bowel disease (IBD). The
      control of small molecules, drugs, released from a polymeric matrix remains a
      great challenge. OBJECTIVE: To study the preparation and properties of a pH
      sensitive carrier for targeting delivery of 5-ASA. MATERIALS AND METHODS: The
      carrier was prepared by ternary blends method based on polyvinyl alcohol (PVA),
      sodium alginate (SA) and polylactic acid. It was characterized by infrared
      spectrometry and scanning electronic microscopy. The adsorption and release of 5
      ASA in different pH media were investigated. RESULTS: We found out the best ratio
      of the materials for synthetic carrier. The vector exhibited good performance by
      the controlled release of the target drug experiment. The adsorption capacity of
      the carrier for 5-ASA was 70.34% in phosphate buffer saline at pH 1.00, and the
      release rate was 100.49% in phosphate buffer solution at pH 6.80. DISCUSSION AND
      CONCLUSION: PVA is vector backbone of the carrier, and SA plays key role in its
      pH performance. It is a promising material to effectively deliver 5-ASA to the
      specific sites of IBD.

PMID- 24320758
TI  - Differing effects of liraglutide on gastric emptying in Japanese patients with
      type 2 diabetes.
AB  - This study was performed to clarify the influence of liraglutide on gastric
      emptying in Japanese patients with type 2 diabetes. In 16 patients, the [(13) C]
      acetate breath test was performed to compare gastric emptying before and after
      liraglutide treatment. We found two patterns of response, with gastric emptying
      being delayed by liraglutide in seven patients (delayers) and not delayed in nine
      patients (non-delayers). The mean increase of the maximum gastric emptying time
      was 31 +/- 4 min (p < 0.01 vs. baseline) in the delayers, while it was only 2 +/-
      3 min (p = 0.60 vs. baseline) in the non-delayers. The delayers showed a greater
      early decrease of AUC-PG from 0 to 60 min, despite no increase of the plasma
      insulin level compared with non-delayers. In conclusion, the effect of
      liraglutide treatment on gastric emptying shows heterogeneity, and patients can
      be classified as delayers or non-delayers. 

PMID- 24320759
TI  - Bullous congenital ichthyosiform erythroderma with rickets: a rare association.

PMID- 24320760
TI  - Evaluation of the serum levels of soluble IL-2 receptor and endothelin-1 in
      children with Crimean-Congo hemorrhagic fever.
AB  - We aimed to assess the association between serum levels of soluble IL-2 receptor
      (sIL-2r) and endothelin-1 and severe infection in children with Crimean-Congo
      hemorrhagic fever (CCHF). Fifty-two patients under 18 years of age with a
      laboratory- confirmed diagnosis of CCHF and 38 healthy controls were enrolled in
      the study. Patients were classified into two groups based on disease severity
      (severe group and non-severe group). The sIL-2r and endothelin-1 levels were
      observed to be significantly higher in patients with severe CCHF compared with
      those with non-severe CCHF and the control group (p < 0.05). In addition, those
      with non-severe CCHF were also found to have a significantly higher sIL-2r level
      relative to the control group (p < 0.001). Although there was a positive
      correlation between sIL-2r and endothelin-1 levels, serum levels of both sIL-2r
      and endothelin-1 were negatively correlated with the platelets count. In children
      with CCHF, serum levels of sIL-2r and endothelin-1 were increased, and this
      increase is related to the severity of the disease. In this study, we concluded
      through prognosis that serum levels of sIL-2r and endothelin-1 might be related,
      and that hemophagocytic lymphohistiocytosis and endothelial injury might
      contribute to a pathogenesis of the disease.

PMID- 24320761
TI  - Relationship between persistent pain and 5-year mortality: a population-based
      prospective cohort study.
AB  - OBJECTIVES: To assess the association between self-reported noncancer pain and 5
      year mortality. DESIGN: Cohort. SETTING: Community-dwelling older adults.
      PARTICIPANTS: Canadian Study of Health and Aging 1996 wave. MEASUREMENTS:
      Registrar of Vital Statistics-established 5-year mortality. Noncancer pain was
      assessed using the 5-point verbal descriptor scale, dichotomized into no or very
      mild versus moderate, severe, or very severe pain. Frailty was the accumulation
      of health deficits. Cognitive status (Modified Mini-Mental State Examination) and
      depressed mood (five-item mental health screening questionnaire) were also
      assessed. Multivariable logistic regression and Cox proportional hazards were
      used to analyze the relationship between pain and 5-year mortality. RESULTS: Of
      5,703 participants, 4,694 (82.3%) had complete data for analysis; 1,663 of these
      (35.4%) reported moderate, severe, or very severe pain, and 1,343 (28.6%) had
      died at 5-year follow-up. Four hundred ninety-six of those who died (29.8%)
      reported moderate, severe, or very severe pain and 847 (27.9%) no or very mild
      pain. Multivariate logistic analysis found that individuals with moderate,
      severe, or very severe pain had lower odds of 5-year mortality than those with no
      or very mild pain (odds ratio=0.78, 95% confidence interval (CI)=0.66-0.92;
      P<.001). The risk of death was lower in persons reporting moderate or greater
      pain than in those with no or very mild pain (HR=0.85, 95% CI=0.75-0.96; P=.01).
      An interaction between pain and sex explained this effect. Men with pain were not
      significantly more likely than men without pain to die (HR=1.00, 95% CI=0.84
      1.19; P=.99), whereas women without pain (HR=0.54, 95% CI=0.47-0.63; P<0.01) and
      women with pain (HR=0.40; CI=0.33-0.47; P<.01) had less risk of death than men
      without and with pain, respectively. CONCLUSION: Older women with pain were less
      likely to die within 5 years than older women without pain, men in pain, or men
      without pain.

PMID- 24320762
TI  - Clarifying the content coverage of differing psychopathy inventories through
      reference to the triarchic psychopathy measure.
AB  - The triarchic model of psychopathy (Patrick, Fowles, & Krueger, 2009) was
      formulated as an integrative framework for reconciling differing conceptions of
      psychopathy. The model characterizes psychopathy in terms of 3 distinguishable
      phenotypic components: boldness, meanness, and disinhibition. Data from a large
      mixed-gender undergraduate sample (N = 618) were used to examine relations of
      several of the best known measures for assessing psychopathic traits with scores
      on the Triarchic Psychopathy Measure (TriPM), an inventory developed to
      operationalize the triarchic model through separate facet scales. Analyses
      revealed that established inventories of psychopathy index components of the
      model as indexed by the TriPM to varying degrees. Although each inventory
      provided effective coverage of meanness and disinhibition components, instruments
      differed in their representation of boldness. Present results demonstrate the
      heuristic value of the triarchic model for delineating commonalities and
      differences among alternative measures of psychopathy and provide support for the
      utility of the triarchic model as a framework for reconciling alternative
      conceptions of psychopathy.

PMID- 24320763
TI  - Validation of interpersonal support evaluation list-12 (ISEL-12) scores among
      English- and Spanish-speaking Hispanics/Latinos from the HCHS/SOL Sociocultural
      Ancillary Study.
AB  - The Interpersonal Support Evaluation List-12 (ISEL-12; Cohen, Mermelstein,
      Kamarck, & Hoberman, 1985) is broadly employed as a short-form measure of the
      traditional ISEL, which measures functional (i.e., perceived) social support. The
      ISEL-12 can be scored by summing the items to create an overall social support
      score; three subscale scores representing appraisal, belonging, and tangible
      social support have also been proposed. Despite extensive use, studies of the
      psychometric properties of ISEL-12 scores have been limited, particularly among
      Hispanics/Latinos, the largest and fastest growing ethnic group in the United
      States. The current study investigated the reliability and structural and
      convergent validity of ISEL-12 scores using data from 5,313 Hispanics/Latinos who
      participated in the Hispanic Community Health Study/Study of Latinos
      Sociocultural Ancillary Study. Participants completed measures in English or
      Spanish and identified their ancestry as Dominican, Central American, Cuban,
      Mexican, Puerto Rican, or South American. Cronbach's alphas suggested adequate
      internal consistency for the total score for all languages and ancestry groups;
      coefficients for the subscale scores were not acceptable. Confirmatory factor
      analyses revealed that the one-factor and three-factor models fit the data
      equally well. Results from multigroup confirmatory factor analyses supported a
      similar one-factor structure with equivalent response patterns and variances
      between language groups and ancestry groups. Convergent validity analyses
      suggested that the total social support score related to scores of social network
      integration, life engagement, perceived stress, and negative affect (depression,
      anxiety) in the expected directions.

PMID- 24320764
TI  - Defining clinical severity in pediatric obsessive-compulsive disorder.
AB  - Despite extensive use of the Children's Yale Brown Obsessive Compulsive Scale
      (CYBOCS; Scahill et al., 1997), the lack of normative data impedes interpretation
      of individual CYBOCS scores. Consequently, psychometrics on CYBOCS severity
      scores from 815 treatment-seeking youth with obsessive-compulsive disorder (OCD)
      are presented, across age and sex, so that normative comparisons of obsessive,
      compulsive, and combined obsessive-compulsive severity could be calculated. Our
      findings suggest no evidence for marked age or sex differences. Further,
      obsessive-compulsive symptom severity scores (measured via the CYBOCS) appear
      consistent with global OCD syndrome severity (measured via the Clinician Global
      Impression-Severity scale [CGI-S; Guy, 1976]; r = .58). This study contributes
      the 1st empirically based guidelines for interpreting obsessive-compulsive
      symptom severity scores. After a diagnosis of OCD is determined, the CYBOCS can
      be used to determine severity of illness (however, categories of severity
      proposed by this article should not be used in the screening of OCD symptoms).
      Findings can facilitate clinicians' and investigators' ability to draw
      comparisons across obsessive-compulsive severity scores.

PMID- 24320766
TI  - Characteristics of current tasks that contribute to mentalizing judgments: does
      the engagement of the participants in the social interaction matter? Comment on
      Achim et al. (2013).
AB  - In a recent article, Achim et al. (2013) discussed the different sources of
      information that contribute to mentalizing judgments in current theory-of-mind
      (ToM) tasks. The authors rightly emphasized the dynamic aspect of real-life
      social interaction, suggesting that taking account of the ongoing changes
      occurring during social interaction would make ToM tasks more ecological. They
      proposed a framework (i.e., the Eight Sources of Information Framework) that
      specifies the 8 sources of information we get from the environment and/or from
      our memories to attribute mental states to others. Nevertheless, we believe that
      a central aspect of ToM is missing in this framework: the engagement (or not) of
      the participant in the social interaction during ToM assessment. Indeed, this
      framework fails to consider how the participant who takes part in the ToM task
      manages this information, depending on the fact that he or she is involved in the
      interaction or not and how the information concerning the agent may impact the
      participant attribution of mental states. We reviewed several arguments and
      results from the ToM literature suggesting that merely observing a social
      interaction is not equivalent to participating in an interaction in terms of
      cognitive processes involved in the attribution of mental states to others.

PMID- 24320765
TI  - Optimizing efficiency of psychopathology assessment through quantitative
      modeling: development of a brief form of the Externalizing Spectrum Inventory.
AB  - The Externalizing Spectrum Inventory (ESI; Krueger, Markon, Patrick, Benning, &
      Kramer, 2007) provides for integrated, hierarchical assessment of a broad range
      of problem behaviors and traits in the domain of deficient impulse control. The
      ESI assesses traits and problems in this domain through 23 lower order facet
      scales organized around 3 higher order dimensions, reflecting general
      disinhibition, callous aggression, and substance abuse. The full-form ESI
      contains 415 items, and a shorter form would be useful for questionnaire
      screening studies or multimethod research protocols. In the current work, we
      employed item response theory and structural modeling methods to create a 160
      item brief form (ESI-BF) that provides for efficient measurement of the ESI's
      lower order facets and quantification of its higher order dimensions either as
      scale-based factors or as item-based composites. The ESI-BF is recommended for
      use in research on psychological or neurobiological correlates of problems such
      as risk-taking, delinquency, aggression, and substance abuse, and studies of
      general and specific mechanisms that give rise to problems of these kinds.

PMID- 24320767
TI  - Real-life interactions and the eight sources of information framework (8-SIF): a
      reply to Champagne-Lavau and Moreau (2013).
AB  - In this response to the comment by Champagne-Lavau and Moreau (2013), we
      acknowledge the importance of ecological mentalizing assessments that allow
      direct interactions between the agent and the person to whom mental states are
      attributed. Furthermore, we clarify that our model, the 8 sources of information
      framework (8-SIF; Achim, Guitton, Jackson, Boutin, & Monetta, 2013), aims to
      document the sources of information on which mentalizing processes can act,
      rather than specifying the numerous affective and cognitive processes involved in
      mentalizing. We argue that the sources of information that can contribute to
      mentalizing judgments during real or realistic interactions are included in the 8
      SIF. The interaction may have an impact on the amount of information from each
      source that is available to the agent, but gaining additional information from a
      given source does not change the type of information or its classification to a
      specific source in the 8-SIF. The point raised by Champagne-Lavau and Moreau
      calls for a new comprehensive model of social cognition that focuses on the
      mentalizing processes, which would nicely complement our model of the sources of
      information on which these processes can act, the 8-SIF.

PMID- 24320773
TI  - Ion-specific effects modulate the diffusive mobility of colloids in an
      extracellular matrix gel.
AB  - The diffusion of colloids in complex biological hydrogels is regulated by a broad
      range of factors including geometric constraints and different types of physical
      interactions between the particles and the hydrogel constituents. As a
      consequence, the particle mobility depends not only on the hydrogel
      microarchitecture but also on the detailed chemical composition of the hydrogel
      solvent. Here, we employ single particle tracking techniques to quantify the
      diffusion behavior of submicrometer-sized particles in such a biological
      hydrogel. We observe three states of colloid mobility: free diffusion, tightly
      and weakly bound particles, and transitions between those states. Finally, by
      comparing the efficiency of particle trapping in Matrigel as a function of the
      ionic strength of the hydrogel buffer, we show that ion-specific effects regulate
      the efficiency of this trapping process. 

PMID- 24320775
TI  - "In theory there is no difference between theory and practice - in practice there
      is" (Yogi Berra).

PMID- 24320774
TI  - Anatomical, physiological and transcriptional responses of two contrasting poplar
      genotypes to drought and re-watering.
AB  - Populus * euramericana (Pe) displays higher stable carbon isotope composition
      (delta(13)C) and intrinsic water use efficiency (WUEi) than Populus cathayana
      (Pc) under unlimited water conditions, rendering us to hypothesize that Pe is
      better acclimated to water deficiency than Pc. To examine this hypothesis,
      saplings of Pc and Pe were exposed to drought and subsequently re-watered. Pc and
      Pe exhibited distinct anatomical, physiological and transcriptional responses in
      acclimation to drought and re-watering, mainly due to stronger responsiveness of
      transcriptional regulation of genes encoding plasma membrane intrinsic proteins
      (PIPs), higher starch accumulation, delta(13)C, stable nitrogen isotope
      composition (delta(15)N) and WUEi , and lower reactive oxygen species (ROS)
      accumulation and scavenging in Pe. In acclimation to drought, both poplar
      genotypes demonstrated altered anatomical properties, declined height growth,
      differential expression of PIPs, activation of ABA signaling pathway, decreased
      total soluble sugars and starch, increased delta(13)C, delta(15)N and WUEi , and
      shifted homeostasis of ROS production and scavenging, and these changes can be
      recovered upon re-watering. These data indicate that Pe is more tolerant to
      drought than Pc, and that anatomical, physiological and transcriptional
      acclimation to drought and re-watering is essential for poplars to survive and
      grow under projected dry climate scenarios in the future.

PMID- 24320776
TI  - Cell tube: a new technique for making cell blocks from needle rinses.

PMID- 24320777
TI  - Pretty in pink. Canine fine needle aspirates of extracellular matrix.

PMID- 24320778
TI  - ASVCP guidelines: quality assurance for point-of-care testing in veterinary
      medicine.
AB  - Point-of-care testing (POCT) refers to any laboratory testing performed outside
      the conventional reference laboratory and implies close proximity to patients.
      Instrumental POCT systems consist of small, handheld or benchtop analyzers. These
      have potential utility in many veterinary settings, including private clinics,
      academic veterinary medical centers, the community (eg, remote area veterinary
      medical teams), and for research applications in academia, government, and
      industry. Concern about the quality of veterinary in-clinic testing has been
      expressed in published veterinary literature; however, little guidance focusing
      on POCT is available. Recognizing this void, the ASVCP formed a subcommittee in
      2009 charged with developing quality assurance (QA) guidelines for veterinary
      POCT. Guidelines were developed through literature review and a consensus
      process. Major recommendations include (1) taking a formalized approach to POCT
      within the facility, (2) use of written policies, standard operating procedures,
      forms, and logs, (3) operator training, including periodic assessment of skills,
      (4) assessment of instrument analytical performance and use of both statistical
      quality control and external quality assessment programs, (5) use of properly
      established or validated reference intervals, (6) and ensuring accurate patient
      results reporting. Where possible, given instrument analytical performance, use
      of a validated 13s control rule for interpretation of control data is
      recommended. These guidelines are aimed at veterinarians and veterinary
      technicians seeking to improve management of POCT in their clinical or research
      setting, and address QA of small chemistry and hematology instruments. These
      guidelines are not intended to be all-inclusive; rather, they provide a minimum
      standard for maintenance of POCT instruments in the veterinary setting. 

PMID- 24320779
TI  - ASVCP guidelines: allowable total error guidelines for biochemistry.
AB  - As all laboratory equipment ages and contains components that may degrade with
      time, initial and periodically scheduled performance assessment is required to
      verify accurate and precise results over the life of the instrument. As
      veterinary patients may present to general practitioners and then to referral
      hospitals (both of which may each perform in-clinic laboratory analyses using
      different instruments), and given that general practitioners may send samples to
      reference laboratories, there is a need for comparability of results across
      instruments and methods. Allowable total error (TEa ) is a simple comparative
      quality concept used to define acceptable analytical performance. These
      guidelines are recommendations for determination and interpretation of TEa for
      commonly measured biochemical analytes in cats, dogs, and horses for equipment
      commonly used in veterinary diagnostic medicine. TEa values recommended herein
      are aimed at all veterinary settings, both private in-clinic laboratories using
      point-of-care analyzers and larger reference laboratories using more complex
      equipment. They represent the largest TEa possible without generating laboratory
      variation that would impact clinical decision making. TEa can be used for (1)
      assessment of an individual instrument's analytical performance, which is of
      benefit if one uses this information during instrument selection or assessment of
      in-clinic instrument performance, (2) Quality Control validation, and (3) as a
      measure of agreement or comparability of results from different laboratories (eg,
      between the in-clinic analyzer and the reference laboratory). These guidelines
      define a straightforward approach to assessment of instrument analytical
      performance. 

PMID- 24320780
TI  - Disease distribution in canine patients with acanthocytosis: 123 cases.
AB  - BACKGROUND: An acanthocyte is an abnormally shaped erythrocyte. In veterinary
      medicine, acanthocytes have historically been associated with canine
      hemangiosarcoma. In human medicine, acanthocytes are rarely observed with
      neoplastic disease and are more commonly associated with a variety of hereditary
      and acquired diseases. OBJECTIVES: The purpose of the study was to determine what
      disease processes are associated with the presence of acanthocytes in the
      peripheral blood of dogs. METHODS: Medical records for dogs presented to the
      Veterinary Teaching Hospital of Colorado State University during January 2004
      through June 2008 with acanthocytes documented in their CBCs were retrospectively
      reviewed. RESULTS: A total of 123 dogs were included, 66 of which were diagnosed
      with neoplastic disease, most commonly hemangiosarcoma (n = 12), osteosarcoma (n
      = 11), and lymphoma (n = 11). The remaining 57 dogs had nonneoplastic disease,
      most commonly observed were gastrointestinal (n = 13), musculoskeletal (n = 8),
      renal (n = 8), and immune-mediated diseases (n = 7). No statistically significant
      difference was detected between percent acanthocytes present in dogs with
      neoplastic and nonneoplastic diseases. CONCLUSION: Acanthocytosis was observed
      with a variety of neoplastic and nonneoplastic diseases. While clearly commonly
      associated, the presence of acanthocytes in a blood smear should not be
      considered pathognomonic for hemangiosarcoma in dogs.

PMID- 24320781
TI  - Comparison of plasma free metanephrines between healthy dogs and 3 dogs with
      pheochromocytoma.
AB  - BACKGROUND: Adrenomegaly and hypertension are common clinical entities in canine
      medicine for which testing for pheochromocytoma is recommended. Yet, a validated
      biochemical test for the diagnosis of pheochromocytoma in dogs does not exist. In
      human medicine, plasma free metanephrine testing is the diagnostic standard for
      the biochemical diagnosis of pheochromocytoma. OBJECTIVES: The purpose of this
      study was to investigate the utility of measurement of plasma free metanephrines
      in dogs for the diagnosis of pheochromocytoma. METHODS: Plasma free metanephrines
      were measured in 11 healthy dogs and in 3 dogs confirmed to have a
      pheochromocytoma. The metanephrine assays were performed at a reference
      laboratory using high-performance liquid chromatography with electrochemical
      detection. RESULTS: The plasma free metanephrine and normetanephrine
      concentrations in 11 healthy dogs were normally distributed and were used to
      create tentative reference intervals. All 3 dogs with histologically confirmed
      pheochromocytoma clearly had higher concentrations of plasma free metanephrines.
      CONCLUSIONS: This pilot study demonstrates the potential utility of plasma free
      metanephrines levels for the biochemical diagnosis of pheochromocytoma in dogs.

PMID- 24320782
TI  - Interference of an algal nutritional supplement with a urinary metabolic
      screening test for glycosaminoglycans in a dog suspected to have a storage
      disease.
AB  - The finding of excess urinary glycosaminoglycans (GAG) is the first step in the
      laboratory diagnosis of mucopolysaccharidosis (MPS). Urinary screening tests are
      based upon the binding of GAG to dimethylmethylene blue. Alternatively, paper
      spot tests using toluidine blue are used in human and veterinary laboratory
      medicine. Positive samples undergo GAG isolation for subsequent characterization.
      Here, we describe a 3-year-old English Cocker Spaniel with a positive urinary GAG
      test, but without other clinical signs of MPS. Urine samples were strongly
      positive with the dimethylmethylene blue test, and isolated GAG subjected to
      electrophoresis on cellulose acetate revealed a band co-migrating with dermatan
      sulfate. However, the isolated GAG were resistant to digestion with
      chondroitinase ABC, suggesting that the band did not represent dermatan sulfate.
      This was confirmed by mobility of the isolated GAG different from dermatan
      sulfate on agarose gel electrophoresis. MPS types VI and VII were excluded by
      enzyme assay. To test the hypothesis of a nutritional source, a healthy control
      dog was fed the same dog food as the index case. His urine showed a comparable
      abnormal GAG screening test and electrophoretic pattern. In addition, the
      analysis of an algal supplement present in the administered dog food showed a
      similar electrophoretic GAG pattern. The Cocker Spaniel was not available for
      further testing after withdrawal of the supplement. Algae contain highly sulfated
      fucans and galactans, and it appears that commercial dog food containing such
      algal, and possibly other, supplements can give rise to false-positive urinary
      MPS screening tests. 

PMID- 24320783
TI  - A mycobacterial coinfection in a dog suspected on blood smear.
AB  - A 4-year-old neutered female crossbred Shepherd was referred for a history of 10
      days of anorexia, polyuria, polydipsia, polyadenomegaly, and diarrhea. On
      physical examination, the dog appeared quiet, responsive, and apyretic, with
      generalized and severe lymphadenomegaly. Hematologic abnormalities included
      neutrophilic leukocytosis with left shift, and lymphopenia. Blood smears revealed
      intracytoplasmic bacilli negatively stained with May-Grunwald-Giemsa in
      neutrophils and monocytes. Lymph node smears revealed pyogranulomatous adenitis
      with calcified deposits and many negative-staining rod structures, both within
      the cytoplasm of neutrophils and macrophages, and free in the background. An acid
      fast stain (Ziehl-Neelsen) confirmed the diagnosis of mycobacterial infection.
      The dog was euthanized for public health and ethical reasons, and the postmortem
      examination revealed severe and generalized granulomatous and necrotizing
      lymphadenitis, panniculitis, and hepatitis, and infiltration of epithelioid
      macrophages in the lungs, colon, and spleen. Numerous acid-fast bacilli,
      consistent with mycobacterial infection, were observed both in the cytoplasm of
      epithelioid macrophages and giant cells, and free in the background.
      Mycobacterium bovis was first confirmed by conventional PCR of organ extracts.
      Mycobacterium avium was detected in a culture of the same organs. Further PCR
      amplifications and sequencing revealed a coinfection with 2 different species of
      mycobacterium, one belonging to the Mycobacterium avium complex and the other to
      the Mycobacterium tuberculosis complex.

PMID- 24320784
TI  - Proportion of mast cells in normal canine hepatic cytologic specimens: comparison
      of 2 staining methods.
AB  - BACKGROUND: Although the presence of mast cells is considered a normal finding in
      canine hepatic tissue, the normal proportion of these cells in cytologic
      specimens from normal livers was not previously established. OBJECTIVES: The
      objective of this study was to determine the normal proportion of hepatic mast
      cells in cytologic specimens from normal canine liver by the use and comparison
      of the May-Grunwald-Giemsa and the Toluidine Blue staining methods. METHODS: The
      cytologic specimens obtained from fine-needle aspirates of livers of 13 healthy
      dogs were investigated by counting of hepatocytes and mast cells per high-power
      field (HPF, x40 objective). The ratio of mast cells/100 hepatocytes was then
      compared between the 2 staining methods. RESULTS: A median of 0.17 (range: 0
      0.33) mast cells/100 hepatocytes and of 0.47 (range: 0-0.86) mast cells/100
      hepatocytes was obtained with May-Grunwald-Giemsa and Toluidine Blue stains,
      respectively. CONCLUSIONS: Toluidine Blue stain detects more hepatic mast cells
      than May-Grunwald-Giemsa in normal canine livers. With both stains, < 1% mast
      cells were detected in normal canine liver samples.

PMID- 24320785
TI  - Recent trends in brand-name and generic drug competition.
AB  - OBJECTIVE: To provide evidence on recent trends in: (1) market exclusivity
      periods (MEPs, the time between launch of a brand-name drug and its first generic
      competitor) for new molecular entities (NMEs); (2) the likelihood and timing of
      patent challenges under Paragraph IV of the Hatch-Waxman Act; and (3) generic
      drug penetration. METHODS: IMS Health National Sales Perspectives data were used
      to calculate MEPs for the 257 NMEs experiencing initial generic entry between
      January 1995 and September 2012 and the number of generic competitors for 12
      months afterwards, by level of annual sales prior to generic entry and time
      period. The likelihood and timing of Paragraph IV challenge were calculated using
      data from Abbreviated New Drug Approval (ANDA) approval letters, the FDA website,
      and public information searches to identify drugs experiencing Paragraph IV
      filings, and the first filing date. RESULTS: For drugs experiencing initial
      generic entry in 2011-2012, the MEP was 12.6 years for drugs with sales greater
      than $100 million (in 2008 dollars) in the year prior to generic entry, 12.9
      years overall. After generic entry, the brand rapidly lost sales, with average
      brand unit share of 16% at 1 year; 11% for NMEs with pre-generic entry sales of
      at least $250 million (in 2008 dollars). Over 80% of NMEs experiencing 2011-2012
      initial generic entry had faced at least one Paragraph IV challenge from a
      generic manufacturer. These challenges were filed relatively early in the brand
      name drug life cycle: within 7 years after brand launch, on average. LIMITATIONS:
      Analyses, including Paragraph IV calculations, were restricted to NMEs where
      generic entry had occurred. CONCLUSION: Pharmaceutical competition continues to
      evolve; while the average MEP below 13 years for 2011-2012 remains consistent
      with prior research, Paragraph IV challenges are increasingly frequent and occur
      earlier, and generic share erosion has intensified.

PMID- 24320786
TI  - Stern layer formation induced by hydrophobic interactions: a molecular level
      study.
AB  - The molecular ionic surface structure and charge of the electric double layer
      around a nanodroplet and its structural change induced by hydrophobic effects are
      measured using vibrational coherent surface scattering spectroscopy, second
      harmonic scattering, and electrokinetic mobility measurements. Tetraalkylammonium
      chloride salts were added to negatively charged nanoscopic oil droplets in water.
      When we vary the alkyl chain length of the cation from CH3 to C4H10, both the
      size of the cation and its hydrophobic interaction are increased. We find that
      tetramethylammonium ions change the electrokinetic potential and the water
      structure but do not detectably adsorb to the interface. Tetrapropylammonium and
      tetrabutylammonium ions clearly adsorb to the interface. The corresponding
      (Stern) layer appears to be a mixed monolayer of anions and cations. An estimate
      of the amount of cations in the Stern layer is also made. 

PMID- 24320787
TI  - Is buprenorphine transdermal patch equally safe and effective in younger and
      elderly patients with osteoarthritis-related pain? Results of an age-group
      controlled study.
AB  - OBJECTIVE: A recent pharmacokinetic study with buprenorphine transdermal patches
      showed similar systemic exposures of buprenorphine in subjects aged >=75 and 50
      60 years. The current prospective, open-label study aimed to verify this in a
      clinical setting by evaluating efficacy and safety of buprenorphine patches in
      patients with chronic osteoarthritis (OA) pain. METHODS: Patients with chronic,
      moderate to severe osteoarthritic pain (hip and/or knee) were enrolled: 50-60
      years (younger group, N = 65) and >=75 years (elderly group, N = 57). After 2
      weeks on paracetamol only, patients received buprenorphine patches (5-40 ug/h)
      for 12 weeks. Paracetamol rescue was provided. Primary endpoint was the Box-Scale
      11 (BS-11) score for pain on average over the last week. WOMAC OA Index, EQ-5D,
      Patients' and Investigators' Global Assessment of Pain Relief, rescue medication
      use, sleep disturbance and quality of sleep were secondary efficacy endpoints.
      RESULTS: Both groups showed a statistically significant (p < 0.0001) and
      clinically relevant change from baseline to last visit in BS-11 score, with no
      significant difference between groups. The least squares (LS) mean change from
      baseline was 2.20 in elderly and 1.87 in younger patients, with an age group
      difference of 0.33 (95% CI: -0.42, 1.07). Non-inferiority of the elderly versus
      the younger group was shown. Both age groups showed a significant improvement in
      WOMAC total score, patients' overall health state (EQ-5D visual analogue scale)
      and sleep quality, and a significant reduction in rescue use and nights woken due
      to pain, with no significant differences between groups. Elderly patients
      tolerated buprenorphine patches at least as well as younger patients.
      CONCLUSIONS: Efficacy and tolerability of buprenorphine patches was demonstrated
      in chronic pain patients, regardless of age, supporting the conclusion that no
      age-related dose adjustment of transdermal buprenorphine is needed. A study
      limitation is lack of active control but no other opioid was appropriate in
      elderly patients or this indication.

PMID- 24320788
TI  - Element misidentification in X-ray crystallography: a reassessment of the
      [MCl2(diazadiene)] (M = Cr, Mo, W) series.
AB  - A series of reports describing the syntheses and structures of [MCl2(diazadiene)]
      (M = Cr, Mo, W) complexes is reassessed in the context of known chemistry of low
      valent Group VI metal complexes, crystallographic trends such as M-Cl bond
      lengths and unit cell volumes, and calculated metal-ligand bond lengths.
      Crystallographic data and computational results are inconsistent with any of
      these species being second or third row transition metal complexes. A review of
      the crystallographic information files accompanying the [MCl2(diazadiene)] (M =
      Mo, W) published structures reveals that the metal atoms were inappropriately
      treated with partial site occupancy factors (0.775 for Mo; 0.4005 and 0.417 for
      W), the effect of which was to manifest lighter-element behavior and better
      refinement in accord with the metal atoms' correct identity. A deliberate
      synthesis and characterization by X-ray diffraction of [ZnCl2((Mes)dad(Me))]
      ((Mes)dad(Me) = 1,4-bis(2,4,6-trimethylphenyl)-2,3-dimethyl-1,4-diaza-1,3
      butadiene) are reported. Refinement of this structure with the same combination
      of second or third row metal and offsetting partial site occupancy is shown to
      provide final refinement statistics essentially the same as with the correct
      model employing M = Zn at site occupancy 1.00. Use of the published method for
      synthesis of [WCl2(diazadiene)] with (Mes)dad(Me) and [WBr4(MeCN)2] in lieu of
      [WCl4(MeCN)2] is shown to produce [ZnBr2((Mes)dad(Me))], which has also been
      characterized by X-ray diffraction. It is concluded that the unusual putative 12
      electron [MCl2(diazadiene)] (M = Cr, Mo, W) complexes are in all cases the
      corresponding [ZnCl2(diazadiene)] complexes, Zn having been commonly employed as
      reducing agent in their synthesis. 

PMID- 24320789
TI  - Utilisation of beds on the general medical unit by 'non-acute medical' patients:
      a retrospective study of incidence and cost in two Tasmanian regional medical
      hospital units.
AB  - BACKGROUND: Demand for healthcare services threatens to overwhelm the Australian
      healthcare system. Public hospitals have the largest component of expenditure
      growth and as such represent the largest opportunity for efficiency gains.
      Utilisation of inpatient hospital beds and in particular those on general medical
      units has not been studied in Australia. AIM: To undertake a retrospective
      patient medical record review of 200 sequential admissions to the medical wards
      in two regional Tasmanian hospitals to determine the incidence of non-acute
      medical patient admission to the medical unit, and the subsequent days in
      hospital that were not required for medical reasons. The cost of these days was
      estimated. RESULTS: Sixteen patient admissions (8%) could not be justified on
      medical grounds. Forty-eight (24%) patient admissions had at least one day
      hospital day that could not be justified on medical grounds. Of the 1438 total
      bed days, 475 (33%) were for non-medical reasons. The estimated cost of those non
      medical bed days for this cohort was $764 800. CONCLUSIONS: The incidence of non
      acute medical admissions and non-acute medical bed days to the medical unit and
      associated cost was significant. Further research is needed to design alternative
      care provision for such patients particularly in regional Australia. The
      potential savings to the Australian healthcare system could be significant.

PMID- 24320790
TI  - Peptide conjugation of 2'-O-methyl phosphorothioate antisense oligonucleotides
      enhances cardiac uptake and exon skipping in mdx mice.
AB  - Antisense oligonucleotide (AON)-mediated exon skipping is a promising therapeutic
      approach for Duchenne muscular dystrophy that is currently being tested in
      various clinical trials. This approach is based on restoring the open reading
      frame of dystrophin transcripts resulting in shorter but partially functional
      dystrophin proteins as found in patients with Becker muscular dystrophy. After
      systemic administration, a large proportion of AONs ends up in the liver and
      kidneys. Therefore, enhancing AON uptake by skeletal and cardiac muscle would
      improve the AONs' therapeutic effect. For phosphorodiamidate morpholino oligomer,
      AONs use nonspecific positively charged cell penetrating peptides to enhance
      efficacy. However, this is challenging for negatively charged 2'-O-methyl
      phosphorothioate oligomer. Therefore, we screened a 7-mer phage display peptide
      library to identify muscle and heart homing peptides in vivo in the mdx mouse
      model and found a promising candidate peptide capable of binding muscle cells in
      vitro and in vivo. Upon systemic administration in dystrophic mdx mice,
      conjugation of a 2'-O-methyl phosphorothioate AON to this peptide indeed improved
      uptake in skeletal and cardiac muscle, and resulted in higher exon skipping
      levels with a significant difference in heart and diaphragm. Based on these
      results, peptide conjugation represents an interesting strategy to enhance the
      therapeutic effect of exon skipping with 2'-O-methyl phosphorothioate AONs for
      Duchenne muscular dystrophy. 

PMID- 24320791
TI  - Imaging diagnosis-an atypical presentation of diffuse idiopathic skeletal
      hyperostosis (dish) in a dog.
AB  - A 10-year-old female spayed Dalmatian was evaluated for progressive cervical
      scoliosis and stiffness. This imaging report describes the imaging and postmortem
      findings for this patient. A diagnosis of an atypical manifestation of diffuse
      idiopathic skeletal hyperostosis (DISH) was made based on imaging and additional
      diagnostics. This report serves to increase awareness of DISH in the veterinary
      community, as well as to describe a unique presentation of the disease with
      atypical lesion distribution and severity. In addition, this report contrasts the
      pathophysiology and imaging characteristics of DISH with spondylosis deformans,
      which can appear comparable radiographically. 

PMID- 24320792
TI  - Immunization of N terminus of enterovirus 71 VP4 elicits cross-protective
      antibody responses.
AB  - BACKGROUND: Enterovirus 71 (EV71) is major cause of hand, foot and mouth disease.
      Large epidemics of EV71 infection have been recently reported in the Asian
      Pacific region. Currently, no vaccine is available to prevent EV71 infection.
      RESULTS: The peptide (VP4N20) consisting of the first 20 amino acids at the N
      terminal of VP4 of EV71 genotype C4 were fused to hepatitis B core (HBcAg)
      protein. Expression of fusion proteins in E. coli resulted in the formation of
      chimeric virus-like particles (VLPs). Mice immunized with the chimeric VLPs
      elicited anti-VP4N20 antibody response. In vitro microneutralization experiments
      showed that anti-chimeric VLPs sera were able to neutralize not only EV71 of
      genotype C4 but also EV71 of genotype A. Neonatal mice model confirmed the
      neutralizing ability of anti-chimeric VLPs sera. Eiptope mapping led to the
      identification of a "core sequence" responsible for antibody recognition within
      the peptide. CONCLUSIONS: Immunization of chimeric VLPs is able to elicit
      antibodies displaying a broad neutralizing activity against different genotypes
      of EV71 in vitro. The "core sequence" of EV71-VP4 is highly conserved across EV71
      genotypes. The chimeric VLPs have a great potential to be a novel vaccine
      candidate with a broad cross-protection against different EV71 genotypes.

PMID- 24320794
TI  - Antenatal calcium intake in Malaysia.
AB  - AIM: To determine the adequacy of antenatal calcium intake in Malaysia, and the
      influencing factors. METHODS: A cross-sectional study was conducted among
      postnatal women who delivered in two tertiary hospitals. Data were collected from
      antenatal cards, hospital documents and diet recall on daily milk and calcium
      intake during pregnancy. SPSS version 19.0 was used for statistical analyses.
      RESULTS: A total of 150 women were studied. The total daily calcium intake was
      834 +/- 43 mg (mean +/- standard error of the mean), but the calcium intake
      distribution curve was skewed to the right with a median intake of 725 mg daily.
      When calcium intake from milk and calcium supplements was excluded, the daily
      dietary calcium intake was only 478 +/- 25 mg. Even with inclusion of milk and
      calcium supplements, more than a third (n=55 or 36.7%) of the women consumed less
      than 600 mg calcium in their daily diet. The adequacy of daily calcium intake was
      not influenced by maternal age, ethnicity, income or maternal job or educational
      status as well as parity. CONCLUSION: The daily dietary calcium intake of the
      Malaysian antenatal population is far from adequate without the addition of
      calcium supplements and milk.

PMID- 24320793
TI  - Construction of tissue-engineered small-diameter vascular grafts in fibrin
      scaffolds in 30 days.
AB  - Tissue-engineered small-diameter vascular grafts have been developed as a
      promising alternative to native veins or arteries for replacement therapy.
      However, there is still a crucial need to improve the current approaches to
      render the tissue-engineered blood vessels more favorable for clinical
      applications. A completely biological blood vessel (3-mm inner diameter) was
      constructed by culturing a 50:50 mixture of bovine smooth muscle cells (SMCs)
      with neonatal human dermal fibroblasts in fibrin gels. After 30 days of culture
      under pulsatile stretching, the engineered blood vessels demonstrated an average
      burst pressure of 913.3+/-150.1 mmHg (n=6), a suture retention (53.3+/-15.4 g)
      that is suitable for implantation, and a compliance (3.1%+/-2.5% per 100 mmHg)
      that is comparable to native vessels. These engineered grafts contained
      circumferentially aligned collagen fibers, microfibrils and elastic fibers, and
      differentiated SMCs, mimicking a native artery. These promising mechanical and
      biochemical properties were achieved in a very short culture time of 30 days,
      suggesting the potential of co-culturing SMCs with fibroblasts in fibrin gels to
      generate functional small-diameter vascular grafts for vascular reconstruction
      surgery. 

PMID- 24320795
TI  - Immobilization of water-soluble HRP within poly-N-isopropylacrylamide microgel
      particles for use in organic media.
AB  - In the present work, the immobilization of enzymes within poly-N
      isopropylacrylamide (p-NIPAM) microgels using the method of solvent exchange is
      applied to the enzyme horseradish peroxidase (HRP). When the solvent is changed
      from water to isopropanol, HRP is embedded within the polymer structure. After
      the determination of the immobilized amount of enzyme, an enhanced specific
      activity of the biocatalyst in isopropanol can be observed. Karl Fischer
      titration is used to determine the amount of water within the microgel particles
      before and after solvent exchange, leading to the conclusion that an "aqueous
      cage" remains within the polymer structure. This represents the driving force for
      the immobilization due to the high affinity of HRP for water. Beside, confocal
      laser scanning microscopy (CLSM) images show that HRP is located within the
      microgel network after immobilization. This gives the best conditions for HRP to
      be protected against chemical and mechanical stress. We were able to transfer a
      water-soluble enzyme to an organic phase by reaching a high catalytic activity.
      Hence, the method of solvent exchange displays a general method for immobilizing
      enzymes within p-NIPAM microgels for use in organic solvents. With this strategy,
      enzymes that are not soluble in organic solvents such as HRP can be used in such
      polar organic solvents. 

PMID- 24320796
TI  - Demographic, clinical, and radiologic signs and treatment responses of lipoid
      proteinosis patients: a 10-case series from Sanliurfa.
AB  - OBJECTIVES: Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis
      characterized by mucocutaneous lesions and hoarseness that develop in early
      childhood. This paper presents the clinical and radiologic characteristics and
      treatment responses of 10 LP patients from five different families. METHODS: Ten
      LP patients followed in our university clinic in Sanliurfa, Turkey, were
      evaluated. Clinical features, as well as histopathologic and radiologic findings,
      were analyzed. Diagnoses were established based on clinical features, with
      histopathologic confirmation in nine cases. The patients were started on
      acitretin at a dose of 0.5 mg/kg/day for six months. RESULTS: Typical cutaneous
      signs of LP and hoarseness of the voice were observed in all patients. No side
      effects associated with the drug were found during treatment. At the end of the
      sixth month, the cutaneous papules and plaques were diminished in seven patients.
      Hoarseness receded in seven patients (particularly in three), vesiculobullous
      lesions were reduced in three patients, and the frequency of oral ulcers
      decreased in three patients. In a patient with palmoplantar hyperkeratosis,
      lesions were found to disappear completely. CONCLUSIONS: We believe acitretin is
      quite effective and reliable in the treatment of cutaneous lesions and hoarseness
      in patients with LP.

PMID- 24320797
TI  - Comparison of antimicrobial susceptibility among Clostridium difficile isolated
      from an integrated human and swine population in Texas.
AB  - Clostridium difficile can be a major problem in hospitals because the bacterium
      primarily affects individuals with an altered intestinal flora; this largely
      occurs through prolonged antibiotic use. Proposed sources of increased community
      acquired infections are food animals and retail meats. The objective of this
      study was to compare the antimicrobial resistance patterns of C. difficile
      isolated from a closed, integrated population of humans and swine to increase
      understanding of the bacterium in these populations. Swine fecal samples were
      collected from a vertically flowing swine population consisting of farrowing,
      nursery, breeding, and grower/finisher production groups. Human wastewater
      samples were collected from swine worker and nonworker occupational group
      cohorts. Antimicrobial susceptibility testing was performed on 523 C. difficile
      strains from the population using the commercially available agar diffusion
      Epsilometer test (Etest((r))) for 11 different antimicrobials. All of the swine
      and human strains were susceptible to amoxicillin/clavulanic acid,
      piperacillin/tazobactam, and vancomycin. In addition, all of the human strains
      were susceptible to chloramphenicol. The majority of the human and swine strains
      were resistant to cefoxitin and ciprofloxacin. Statistically significant
      differences in antimicrobial susceptibility were found among the swine production
      groups for ciprofloxacin, tetracycline, amoxicillin/clavulanic acid, and
      clindamycin. No significant differences in antimicrobial susceptibility were
      found across human occupational group cohorts. We found that 8.3% of the swine
      strains and 13.3% of the human strains exhibited resistance to metronidazole. The
      finding of differences in susceptibility patterns between human and swine strains
      of C. difficile provides evidence that transmission between host species in this
      integrated population is unlikely.

PMID- 24320798
TI  - Survival of methicillin-resistant Staphylococcus aureus during thermal processing
      of frankfurters, summer sausage, and ham.
AB  - Infections from antibiotic-resistant bacteria are a major concern for human
      health professionals around the world. Methicillin-resistant Staphylococcus
      aureus (MRSA) is just one of the resistant organisms of concern. MRSA prevalence
      has also been recently reported in retail meat products at rates higher than
      originally thought. Although the risk of contracting an infection from handling
      contaminated meat products is thought to be low, very little is known about this
      organism from a food safety perspective. The objective of this study was to
      determine the survival of MRSA during thermal processing of frankfurters, summer
      sausage, and boneless ham. Frankfurters, summer sausage, and boneless ham were
      manufactured using formulations and processing procedures developed at the Iowa
      State University meat laboratory. Thermal processing resulted in a significant
      log reduction (p<0.05) for boneless ham, summer sausage, and frankfurters when
      compared to uncooked, positive controls for each of the three processed meat
      products. All products were thermally processed to an internal temperature of 70
      degrees C and promptly cooled to 7.2 degrees C. Boneless ham showed the highest
      log reduction (7.28 logs) from cooking, followed by summer sausage (6.75 logs)
      and frankfurters (5.53 logs). The results of this study indicate that thermal
      processing of ham, summer sausage, and frankfurters to 70 degrees C is sufficient
      to reduce the risk of MRSA as a potential food safety hazard.

PMID- 24320799
TI  - Surface plasmon enhanced organic solar cells with a MoO3 buffer layer.
AB  - High-efficiency surface plasmon enhanced 1,1-bis-(4-bis(4-methyl-phenyl)-amino
      phenyl)-cyclohexane:C70 small molecular bulk heterojunction organic solar cells
      with a MoO3 anode buffer layer have been demonstrated. The optimized device based
      on thermal evaporated Ag nanoparticles (NPs) shows a power conversion efficiency
      of 5.42%, which is 17% higher than the reference device. The improvement is
      attributed to both the enhanced conductivity and increased absorption due to the
      near-field enhancement of the localized surface plasmon resonance of Ag NPs. 

PMID- 24320800
TI  - Staphylococcal biofilm formation as affected by type acidulant.
AB  - Staphylococcal growth and biofilm formation in culture medium where pH was
      lowered with weak organic (acetic and lactic) or strong inorganic (hydrochloric)
      acids were studied. The effects were evaluated by biomass measurements, cell
      surface hydrophobicity, scanning electron microscopy (SEM), and confocal laser
      scanning microscopy (CLSM). The results demonstrated that the inhibition was
      related to type of acidulant and pH value. At pH 5.0, the antibacterial effect
      was more pronounced in the presence of acetic acid (58-60% growth reduction)
      compared with that in the presence of lactic (7-16% growth reduction) and
      hydrochloric acids (23-24% reduction). The biofilm biomass of Staphylococcus
      aureus and Staphylococcus epidermidis was reduced by 92, 85, 63, and 93, 87, 81%
      after exposition to acetic, lactic, and hydrochloric acids, respectively.
      Increasing the pH from 5.0 to 6.0 resulted in a noticeable reduction in the
      effectiveness of acids. A minor cells hydrophobic character was also documented.
      The SEM and CLSM revealed a poorly structured and thinner biofilm compared with
      the dense and multilayered control. Acidic environment could have important
      implications for food-processing system to prevent bacterial colonization and
      control biofilm formation. The findings of this study lead to consider the
      rational use of the type of acid to achieve acidic environments.

PMID- 24320801
TI  - Effects of low-level laser therapy on biceps braquialis muscle fatigue in young
      women.
AB  - OBJECTIVE: This study aims to investigate the effects of low-level laser therapy
      (LLLT) on biceps brachi muscular fatigue in 20 young females. BACKGROUND DATA:
      Exhausting physical activity leads to muscular fatigue, which could decrease
      muscular strength, and may cause impairment in motor control and muscle pain.
      Several biochemical and biophysical resources have been studied in an attempt to
      accelerate the recovery of muscle fatigue. Among these, LLLT is emphasized.
      METHODS: Twenty subjects were randomized in one laser group and one placebo group
      in two sessions of a crossover design experimental procedure; the second session
      taking place within 7 days of the first. In the first session, subjects underwent
      a collection of surface electromyographic (SEMG) data of the biceps brachii
      muscle, followed by active or placebo LLLT at the same muscle, followed then by
      another EMG sample of biceps brachii. Blood samples were collected five times
      during the experimental procedure. Second session procedures were identical to
      the first, with exception of LLLT, which was the opposite of the first session.
      The fatigue protocol consisted of 60 sec of elbow flexion-extension movement
      performed with 75% of one maximum repetition. Blood lactate, EMG fatigue, and the
      number of elbow flexion-extension repetitions during the fatigue protocol were
      used to evaluate the effects of laser therapy (808 nm wavelength, 100 mW output
      power, power density of 35.7 W/cm(2), 70 sec each point and 7 J/point on eight
      points). RESULTS: No statistical differences were found for eletromyographic
      fatigue and blood lactate values between groups. Mean numbers of elbow flexion
      extension repetitions were 22.6 +/- 7.58 after placebo, and 25.1 +/- 9.89 after
      active LLLT group, but these differences were not statistically significant
      (p=0.342). CONCLUSIONS: LLLT had limited effects on delaying muscle fatigue in a
      young female sample, although a tendency was observed in the active laser group
      toward showing lower electromyography fatigue of biceps brachii muscle. No
      intergroup differences were found in the number of muscle contractions and
      lactate concentration.

PMID- 24320802
TI  - A retrospective evaluation of benign prostatic hyperplasia treatment by
      transurethral vaporization using a 1470 nm laser.
AB  - OBJECTIVE: This article aims to evaluate the safety and efficacy of a new diode
      laser at a wavelength of 1470 nm, in the surgical treatment of benign prostatic
      hyperplasia (BPH). BACKGROUND DATA: BPH is very common. Laser surgeries, such as
      photoselective vaporization of the prostate (PVP), have gained interest over the
      past decade because of their satisfying clinical results and reduced morbidity.
      METHODS: A total of 24 patients who underwent transurethral vaporization of the
      prostate with a new diode laser prototype at a wavelength of 1470 nm were
      included in this retrospective study. The baseline characteristics of patients
      and treatment outcomes were evaluated at 4 weeks after the operation with the
      International Prostate Symptoms Score (IPSS), duration of catheterization, and
      maximum urinary flow rate (Qmax). RESULTS: The mean age of patients was 69 +/-
      8.6 years. The mean time of operation and hospitalization were 97 +/- 39 min and
      5.3 +/- 5.2 days, respectively. The mean duration of catheterization after
      surgery was 3.1 +/- 2.7 days. No recatheterizations or secondary surgeries were
      required. IPSS and Qmax at 4 weeks postoperatively were significantly changed
      compared with the baseline (p<0.001). CONCLUSIONS: Transurethral vaporization of
      the prostate using a 1470 nm laser is effective to treat benign prostatic
      hyperplasia.

PMID- 24320806
TI  - The sarcoidal variant of annular elastolytic granuloma.

PMID- 24320807
TI  - Connect the dots.

PMID- 24320808
TI  - Hypopigmented mycosis fungoides in childhood and adolescence: a long-term
      retrospective study.
AB  - Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than
      those with classic MF. Our goal was to describe the clinical presentation,
      histopathologic features and long-term outcome in patients who developed HMF
      before the age of 21. It was observed that among 69 pediatric patients diagnosed
      with MF between 1992 and 2010, 50 had HMF. Thirty-five patients had clinical
      follow-up. There were 37 males and 32 females with a mean age of 13.6 years. Most
      patients were African American or Hispanic and presented with multiple
      hypopigmented patches. All biopsies showed epidermotropism of T-lymphocytes,
      whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested
      were CD8+. Treatment modalities included topical steroids, narrow band
      ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1
      12 years. Most children responded to treatment, but recurrence rates were high.
      One patient progressed to plaque/tumor stage. Others did not progress; however,
      many were lost to follow-up. We present a large cohort of children with HMF and
      report on the features of disease and progression. A major difference in
      histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably
      because of presentation in the early patch stage. Most patients have a waxing-and
      waning course and relapse after discontinuation of therapy, requiring repetitive
      treatment. 

PMID- 24320809
TI  - Panfollicular carcinoma or trichoblastic carcinoma with panfollicular
      differentiation?
AB  - Herein, we report two cases of a follicular neoplasm with panfollicular
      differentiation showing architectural and cytologic findings suggestive of a
      malignancy. Immunohistochemical analysis of beta-catenin expression in the
      neoplasm showed nuclear and cytoplasmic immunoreactivity, with no reactivity in
      the transitional and shadow cells, consistent with beta-catenin expression of
      pilomatrical tumors. Staining for BerEp4 was positive at the periphery of both
      neoplasms, suggesting germinative differentiation of the neoplastic cells,
      whereas staining for the follicular stem-cell marker PHLDA-1 (TDAG51) showed
      strong focal expression in the tumor cells of both cases. Given these findings,
      these neoplasms show features of both panfollicular neoplasms and basal cell
      carcinoma with panfollicular/matrical differentiation. These are the first cases
      of this neoplasm reported to date. More reports are needed to assess their
      malignant potential. 

PMID- 24320810
TI  - Measuring and monitoring blood utilization.

PMID- 24320811
TI  - Platelet transfusion volume reduction: it can be done, but why do it?

PMID- 24320812
TI  - Fresh blood or old blood? How shall we manage the inventories?

PMID- 24320813
TI  - Transfusion medicine illustrated: Transfusion interference by cold agglutinins.

PMID- 24320814
TI  - How we view and approach transfusion-associated circulatory overload:
      pathogenesis, diagnosis, management, mitigation, and prevention.

PMID- 24320815
TI  - Red blood cell alloimmunization in sickle cell disease-prevalence and trends: a
      single-center cross-sectional study from United Kingdom.

PMID- 24320816
TI  - Why do thrombocytopenic patients bleed?

PMID- 24320817
TI  - High-resolution mass spectrometric investigation of the phase I and II
      metabolites of finasteride in pig plasma, urine and bile.
AB  - 1. The metabolite profile of the 5alpha-reductase type II inhibitor finasteride
      has been studied in pig plasma, urine and bile using high-resolution mass
      spectrometry. The porcine biotransformation products were compared to those
      formed by human liver microsomes and to literature data of recently identified
      human in vivo metabolites. The objective of this study was to gain further
      evidence for the validity of using pigs for advanced, invasive drug-drug
      interaction studies that are not possible to perform in humans. 2. The use of
      high-resolution mass spectrometry with accurate mass measurements enabled
      identification of the metabolites by calculation of their elemental compositions
      as well as their fragmentation patterns. 3. There was an excellent match between
      the porcine and human metabolic profiles, corroborating the pig as a model of
      human drug metabolism. The glucuronides of the two recently described human
      hydroxylated metabolites MX and MY and the carboxylated metabolite M3 were
      identified as the major biotransformation products of finasteride in pig urine
      and bile. 4. Furthermore, the CYP enzymes involved in the formation of the
      hydroxylated metabolites were characterized. Human recombinant CYP3A4 could
      produce the two major hydroxylated metabolites MX and MY, whereas human
      recombinant CYP2D6 formed MY only.

PMID- 24320818
TI  - Adams-Oliver syndrome.

PMID- 24320819
TI  - Health-related quality of life and functional status quality indicators for older
      persons with multiple chronic conditions.
AB  - OBJECTIVES: To explore central challenges with translating self-reported
      measurement tools for functional status and health-related quality of life
      (HRQOL) into ambulatory quality indicators for older people with multiple chronic
      conditions (MCCs). DESIGN: Review. SETTING: Sources including the National
      Quality Measures Clearinghouse and National Quality Forum were reviewed for
      existing ambulatory quality indicators relevant to functional status, HRQOL, and
      people with MCCs. PARTICIPANTS: Seven informants with expertise in indicators
      using functional status and HRQOL. MEASUREMENTS: Informant interviews were
      conducted to explore knowledge about these types of indicators, particularly
      usability and feasibility. RESULTS: Nine important existing indicators were
      identified in the review. For process, identified indicators addressed whether
      providers assessed functional status; outcome indicators addressed quality of
      life. In interviews, informants agreed that indicators using self-reported data
      were important in this population. Challenges identified included concerns about
      usability due to inability to discriminate quality of care adequately between
      organizations and feasibility concerns regarding high data collection burden,
      with a correspondingly low response rate. Validity was also a concern because
      evidence is mixed that healthcare interventions can improve HRQOL or functional
      status for this population. As a possible first step, a structural standard could
      be systematic collection of these measures in a specific setting. CONCLUSION:
      Although functional status and HRQOL are important outcomes for older people with
      MCCs, few relevant ambulatory quality indicators exist, and there are concerns
      with usability, feasibility, and validity. Further research is needed on how best
      to incorporate these outcomes into quality indicators for people with MCCs.

PMID- 24320820
TI  - Increased diverticular complications with nonsteriodal anti-inflammatory drugs
      and other medications: a systematic review and meta-analysis.
AB  - AIM: Complications of colonic diverticula, perforation and bleeding are a source
      of morbidity and mortality. A variety of drugs have been implicated in these
      complications. We present a systemic review and meta-analysis of the literature
      to assess the importance of this relationship. METHOD: A systematic review of
      articles in PubMed, Cochrane Reviews, Embase and Google Scholar was undertaken in
      February 2013. An initial literature search yielded 2916 results that were
      assessed for study design and topicality. Twenty-three articles were included in
      the review. A qualitative data synthesis was conducted using forest plots of
      studies comparing single medication with complications. RESULTS: Individual
      studies demonstrated the odds of perforation and abscess formation with
      nonsteridal anti-inflammatory drugs (NSAIDs) (1.46-10.30), aspirin (0.66-2.40),
      steroids (2.17-31.90) and opioids (1.80-4.51) and the odds of bleeding with
      NSAIDs (2.01-12.60), paracetamol (0-3.75), aspirin (1.14-3.70) and steroids (0.57
      5.40). Pooled data showed significantly increased odds of perforation and abscess
      formation with NSAIDs (OR = 2.49), steroids (OR = 9.08) and opioids (OR = 2.52).
      They also showed increased odds of diverticular bleeding from NSAIDs (OR = 2.69),
      aspirin (OR = 3.24) and calcium-channel blockers (OR = 2.50). Most studies did
      not describe the duration or dosage of medication used and did not systematically
      describe the severity of diverticular complications. CONCLUSION: Various common
      medications are implicated in complications of diverticular disease.

PMID- 24320821
TI  - Role of absorbed solvent in polymer pen lithography.
AB  - We report on the dynamic role of solvents in molecular printing and show that
      material transport can be mediated by both environmental solvent (i.e., humidity)
      and solvent absorbed in the pen. To explore the transport of materials in the
      absence of environmental solvent, a hydrophobic polymer was patterned using a
      polydimethylsiloxane (PDMS) pen array that had been soaked in undecane, a
      nonpolar solvent that readily absorbs into PDMS. We also explored the patterning
      of the hydrophilic polymer polyethylene glycol (PEG) and found that, even though
      PDMS only absorbs trace amounts of water, soaking a PDMS pen array in water
      enables PEG deposition in completely dry environments for over 2 h. We find that
      the length of time one can pattern in a dry environment is determined by the
      availability of absorbed solvent, a relationship that we elucidate by comparing
      the performance of pens with varying ability to absorb water. Furthermore, a
      calculation accounting for the dynamics of retained water captures these effects
      completely, allowing for generalization of this result to other solvents and
      providing a way to tune the desired solvent retention profile. Taken together,
      this work explores the subtle and dynamic role of solvent on molecular printing
      and provides an alternative to strict environmental humidity control for reliable
      molecular printing. 

PMID- 24320822
TI  - Objective measurements for grading the nasal esthetics on Basal view in
      individuals with secondary cleft nasal deformity.
AB  - OBJECTIVE: The purpose of this study is to ascertain objective nasal measurements
      from the basal view that are predictive of nasal esthetics in individuals with
      secondary cleft nasal deformity. DESIGN: Thirty-three patients who had undergone
      unilateral cleft lip repair were retrospectively reviewed in this study. The
      degree of nasal deformity was subjectively ranked by seven surgeons using
      standardized basal-view measurements. Nine physical objective parameters
      including angles and ratios were measured. Correlations and regressions between
      these objective and subjective measurements were then analyzed. RESULTS: There
      was high concordance in subjective measurements by different surgeons (Kendall's
      harmonious coefficient = W = .825, P = .006). The strongest predictive factors
      for nasal aesthetics were the ratio of length of nasal alar (r = .370, P = .034)
      and the degree of deviation of the columnar axis (r = .451, P = .008). The
      columellar angle had a more powerful effect in rating nasal esthetics.
      CONCLUSION: There was reliable concordance in subjective ranking of nasal
      esthetics by surgeons. Measurement of the columnar angle may serve as an
      independent, objective predictor of esthetics of the nose.

PMID- 24320823
TI  - Carbon dioxide capture by an amine functionalized ionic liquid: fundamental
      differences of surface and bulk behavior.
AB  - Carbon dioxide (CO2) absorption by the amine-functionalized ionic liquid (IL)
      dihydroxyethyldimethylammonium taurinate at 310 K was studied using surface- and
      bulk-sensitive experimental techniques. From near-ambient pressure X-ray
      photoelectron spectroscopy at 0.9 mbar CO2, the amount of captured CO2 per mole
      of IL in the near-surface region is quantified to ~0.58 mol, with ~0.15 mol in
      form of carbamate dianions and ~0.43 mol in form of carbamic acid. From
      isothermal uptake experiments combined with infrared spectroscopy, CO2 is found
      to be bound in the bulk as carbamate (with nominally 0.5 mol of CO2 bound per 1
      mol of IL) up to ~2.5 bar CO2, and as carbamic acid (with nominally 1 mol CO2
      bound per 1 mol IL) at higher pressures. We attribute the fact that at low
      pressures carbamic acid is the dominating species in the near-surface region,
      while only carbamate is formed in the bulk, to differences in solvation in the
      outermost IL layers as compared to the bulk situation.

PMID- 24320824
TI  - Health status, late effects and long-term survivorship of allogeneic bone marrow
      transplantation: a retrospective study.
AB  - BACKGROUND: Survival after allogeneic haemopoietic stem cell transplantation
      (allo-HSCT) has improved because of advancements in allo-HSCT. Allo-HSCT has been
      performed in Australia since the late 1970s. However, there are few published
      data about health problems of allo-HSCT survivors in Australia. AIMS: Identify
      health issues in long-term survivors of allo-HSCT in an Australian centre to
      manage better and prevent long-term complications. METHODS: The health records of
      all patients of allo-HSCT in a single centre from January 2000 to December 2007
      and survived beyond 2 years were assessed. RESULTS: Ninety-nine of the 200 allo
      HSCT patients survived beyond 2 years, and the median time from allo-HSCT was 74
      months. Twenty-eight per cent died at a median of 37 months after allo-HSCT
      because of relapsed malignancy (12%), stroke (1%), infection (3%), chronic graft
      versus host disease (9%), secondary malignancy (2%) and unknown cause (1%).
      Ninety-one per cent reported one or more chronic health conditions. Health issues
      were chronic graft versus host disease (70%); respiratory (66%), ophthalmic
      (40%), bone (33%), and renal (26%) problems; and malignancies (14% skin, 3% solid
      organ). Seventy-nine per cent resumed vocation at full or reduced capacity 2
      years after allo-HSCT. Clinicians identified 40% with quality of life (QOL)
      issues, but survivors' self-reported QOL was comparable with the general
      Australian population. CONCLUSION: This study shows that allo-HSCT patients are
      living with high burdens of chronic diseases that warrant lifelong surveillance
      and engagement with healthcare. Structured, multi-disciplinary care as
      recommended by published guidelines for allo-HSCT survivors may reduce long-term
      effects and improve their outcomes.

PMID- 24320826
TI  - Biphasic self-assembly pathways and size-dependent photophysical properties of
      perylene bisimide dye aggregates.
AB  - The concentration-dependent absorption and temperature-dependent fluorescence of
      the perylene bisimide dye PBI 1 in methylcyclohexane point to a biphasic
      aggregation behavior. At intermediate concentrations and temperatures,
      respectively, a dimer with low fluorescence yield dominates, which cannot be
      extended to longer aggregates. Those are formed at high concentrations and low
      temperatures, respectively, via a second, energetically unfavorable dimer species
      that acts as a nucleus. A corresponding aggregation model reproduces accurately
      the concentration dependence and allows extracting the equilibrium constants and
      spectra of the distinct species. The differences in the photophysical properties
      indicate H-type excitonic coupling for the favored dimer and J-type
      characteristics for the extended aggregates which could be related to structural
      models based on DFT calculations. The energetics can be understood by considering
      hydrogen-bonding and pi-pi-stacking interactions. 

PMID- 24320825
TI  - Recellularization of well-preserved acellular kidney scaffold using embryonic
      stem cells.
AB  - For chronic kidney diseases, there is little chance that the vast majority of
      world's population will have access to renal replacement therapy with dialysis or
      transplantation. Tissue engineering would help to address this shortcoming by
      regeneration of damaged kidney using naturally occurring scaffolds seeded with
      precursor renal cells. The aims of the present study were to optimize the
      production of three-dimensional (3D) rat whole-kidney scaffolds by shortening the
      duration of organ decellularization process using detergents that avoid nonionic
      compounds, to investigate integrity of extracellular matrix (ECM) structure and
      to enhance the efficacy of scaffold cellularization using physiological perfusion
      method. Intact rat kidneys were successfully decellularized after 17 h perfusion
      with sodium dodecyl sulfate. The whole-kidney scaffolds preserved the 3D
      architecture of blood vessels, glomeruli, and tubuli as shown by transmission and
      scanning electron microscopy. Micro-computerized tomography (micro-CT) scan
      confirmed integrity, patency, and connection of the vascular network. Collagen
      IV, laminin, and fibronectin staining of decellularized scaffolds were similar to
      those of native kidney tissues. After infusion of whole-kidney scaffolds with
      murine embryonic stem (mES) cells through the renal artery, and pressure
      controlled perfusion with recirculating cell medium for 24 and 72 h, seeded cells
      were almost completely retained into the organ and uniformly distributed in the
      vascular network and glomerular capillaries without major signs of apoptosis.
      Occasionally, mES cells reached peritubular capillary and tubular compartment. We
      observed the loss of cell pluripotency and the start of differentiation toward
      meso-endodermal lineage. Our findings indicate that, with the proposed optimized
      protocol, rat kidneys can be efficiently decellularized to produce renal ECM
      scaffolds in a relatively short time, and rapid recellularization of vascular
      structures and glomeruli. This experimental setup may open the possibility to
      obtain differentiation of stem cells with long lasting in vitro perfusion. 

PMID- 24320827
TI  - Nickel affects xylem Sap RNase a and converts RNase A to a urease.
AB  - BACKGROUND: Nickel (Ni) is an essential micronutrient; however, its metabolic or
      physiological functions in plants and animals are largely uncharacterized. The
      ribonucleases (RNase, e.g., RNase A) are a large family of hydrolases found in
      one form or many forms facilitating nitrogen (N) cycling. It is currently unknown
      how either a deficiency or excess of Ni influences the functionality of
      ribonucleases, like RNase A. This is especially true for perennial crops
      possessing relatively high Ni requirements. RESULTS: We report that the 'rising'
      xylem sap of pecan [Carya illinoinensis (Wangenh.) K. Koch, a long-lived tree] at
      bud break contains a 14 kDa RNase A (aka, RNase 1), which amount has a 33%
      greater in Ni-deficient as in Ni-sufficient trees when exposed to Ni ions
      exhibits ureolytic activity. The homologous 13.4 kDa bovine pancreatic RNase A
      likewise exhibits ureolytic activity upon exposure to Ni ions. Ni therefore
      affects enzymatic function of a typically non-metalloenzyme, such as it
      transforms to an enzyme capable of hydrolyzing a linear amide; thus, converting
      an endonuclease esterase into a urease. CONCLUSIONS: We conclude that Ni
      potentially affects the level and activity of RNase A present in the spring xylem
      sap of pecan trees, and probably in other crops, it has the same influence. The
      catalytic property of RNase A appears to shift from a nuclease to a urease
      relying on Ni exposure. This is suggestive that RNase A might possess novel
      metabolic functionality regarding N-metabolism in perennial plants. The ability
      of Ni to convert the activity of plant and animal RNase A from that of a
      ribonuclease to a urease indicates a possible unrecognized beneficial metabolic
      function of Ni in organisms, while also identifying a potential detrimental
      effect of excessive Ni on N related metabolic activity if there is sufficient
      disruption of Ni homeostasis.

PMID- 24320828
TI  - Association between oral DNA-HPV and genital DNA-HPV.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is one of the most common
      sexually transmitted diseases worldwide and is observed in both men and women.
      The presence of the virus is often associated with benign and malignant neoplasms
      of the oral cavity. We wished to investigate whether HPV infection in the
      genitalia was associated with HPV infection in the oral mucosa. METHODS: The
      prevalence of HPV in the oral cavity and genitalia was evaluated by DNA
      extraction from genital and oral cavity samples of 105 women, followed by nested
      PCR. RESULTS AND CONCLUSIONS: The prevalence of HPV in the oral cavity was
      significantly higher in women who had genital HPV (P < 0.0001). Oral sex,
      alcohol, and tobacco consumption were not associated with the oral HPV infection.

PMID- 24320829
TI  - Stochastic adhesion of hydroxylated atomic force microscopy tips to supported
      lipid bilayers.
AB  - This work reports results of an atomic force microscopy (AFM) study of adhesion
      force between hydroxylated AFM tips and supported lipid bilayers (SLBs) of
      phosphatidylcholine in phosphate buffer saline solution at neutral pH. Silicon
      nitride AFM probes were hydroxylated by treatment in water vapor plasma and used
      in force spectroscopy measurements of adhesion force on SLBs with control of
      contact loading force and residence time. The measurements showed a stochastic
      behavior of adhesion force that was attributed to stochastic formation of
      hydrogen bonds between the hydroxyl groups on the AFM tip and oxygen atoms from
      the phosphate groups of the phosphatidylcholine molecules. Analysis of a large
      number of force curves revealed a very low probability of hydrogen bond
      formation, a probability that increased with the increase of contact loading
      force and residence time. The variance and mean values of adhesion force showed a
      linear dependence on each other, which indicated that hydrogen bond formation
      obeyed the Poisson distribution of probability. This allowed for the quantitative
      determination of the rupture force per hydrogen bond of about 40 pN and showed
      the absence of other nonspecific interaction forces. 

PMID- 24320830
TI  - Introduction to the special issue on illness self-management.
AB  - The active involvement of consumers with a serious mental illness as partners in
      their own treatment and the facilitation of illness self-management strategies
      are hallmarks of recovery-oriented services. The articles in this special issue
      are evidence of the explosion in the development, evaluation, adaptation, and
      implementation of programs aimed at improving the ability of consumers to manage
      psychiatric, medical, and substance use disorders in collaboration with others.
      Illness self-management is a critical ingredient to consumers taking control over
      their own lives and fostering genuine collaboration with professionals in their
      treatment.

PMID- 24320831
TI  - Consumer and provider responses to a computerized version of the Illness
      Management and Recovery Program.
AB  - OBJECTIVE: To explore mental health consumer and provider responses to a
      computerized version of the Illness Management and Recovery (IMR) program.
      METHOD: Semistructured interviews were conducted to gather data from 6 providers
      and 12 consumers who participated in a computerized prototype of the IMR program.
      An inductive-consensus-based approach was used to analyze the interview
      responses. RESULTS: Qualitative analysis revealed consumers perceived various
      personal benefits and ease of use afforded by the new technology platform.
      Consumers also highly valued provider assistance and offered several suggestions
      to improve the program. The largest perceived barriers to future implementation
      were lack of computer skills and access to computers. Similarly, IMR providers
      commented on its ease and convenience, and the reduction of time intensive
      material preparation. Providers also expressed that the use of technology creates
      more options for the consumer to access treatment. CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: The technology was acceptable, easy to use, and well-liked by
      consumers and providers. Clinician assistance with technology was viewed as
      helpful to get clients started with the program, as lack of computer skills and
      access to computers was a concern. Access to materials between sessions appears
      to be desired; however, given perceived barriers of computer skills and computer
      access, additional supports may be needed for consumers to achieve full benefits
      of a computerized version of IMR.

PMID- 24320832
TI  - A randomized controlled trial of an adapted Illness Management and Recovery
      program for people with schizophrenia awaiting discharge from a psychiatric
      hospital.
AB  - OBJECTIVE: Most research on the Illness Management and Recovery (IMR) program for
      people with severe mental illnesses has focused on individuals with stable
      symptoms living in the community, with less attention to persons being treated in
      an inpatient setting. We evaluated the feasibility and effects of an IMR program
      adapted for individuals with schizophrenia who were awaiting discharge into the
      community. METHOD: A randomized controlled trial was conducted at 2 hospitals in
      Taiwan to compare the adapted IMR program with treatment as usual (TAU). Ninety
      seven individuals with schizophrenia were randomized to the adapted IMR program
      or TAU. Four outcome indicators including illness-management knowledge, attitudes
      toward medication, insight, and symptoms were assessed at baseline,
      posttreatment, and at a 1-month follow-up following discharge from the hospital.
      RESULTS: Participants in the adapted IMR group showed significantly greater
      improvements at posttreatment and 1-month follow-up in illness-management
      knowledge, attitudes toward medication, insight, and negative symptoms on the
      Brief Psychiatric Rating Scale (BPRS) than individuals in the TAU group. There
      were no significant differences between the 2 groups on other subscales of the
      BPRS. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This is the first controlled
      evaluation of a version of the IMR program in an East Asian culture, and the
      first to evaluate it in an acute care inpatient setting. Our findings support the
      feasibility and potential benefits of implementing an adapted IMR program,
      focused on the prevention of relapses and rehospitalizations, during the
      discharge period of an inpatient treatment stay to prepare individuals to reenter
      the community.

PMID- 24320833
TI  - Impact of Wellness Recovery Action Planning on service utilization and need in a
      randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to assess the impact of a mental illness
      self-management intervention, called Wellness Recovery Action Planning (WRAP), on
      the use of and need for mental health services over time compared with nutrition
      and wellness education. METHOD: Participants were recruited from outpatient
      community mental health settings in Chicago, Illinois. Using a single-blind,
      randomized controlled trial design, 143 individuals were assigned to WRAP or to a
      nutrition education course and assessed at baseline and at 2-month and 8-month
      follow-up. The WRAP intervention was delivered by peers in recovery from serious
      mental illness who were certified WRAP educators over nine weekly sessions
      lasting 2.5 hrs. The nutrition education curriculum was taught by trained non
      peer educators using the same schedule. Mixed-effects random regression analysis
      tested for differences between the two interventions in (a) self-reported use of
      19 clinical, rehabilitation, peer, emergent, and ancillary services; and (b) self
      reported need for these services. RESULTS: Results of mixed-effects random
      regression analysis indicated that, compared with controls, WRAP participants
      reported significantly greater reduction over time in service utilization (total,
      individual, and group), and service need (total and group services). Participants
      in both interventions improved significantly over time in symptoms and recovery
      outcomes. DISCUSSION: Training in mental illness self-management reduced the self
      reported need for and use of formal mental health services over time. This
      confirms the importance of WRAP in an era of dwindling behavioral health service
      availability and access.

PMID- 24320834
TI  - Integrating personal medicine into service delivery: empowering people in
      recovery.
AB  - OBJECTIVE: Illness management and recovery strategies are considered evidence
      based practices. The article describes how a web-based application, CommonGround,
      has been used to support implementation of such strategies in outpatient mental
      health services and assess its impact. The specific focus of this article is
      Personal Medicine, self-management strategies that are a salient component of the
      CommonGround intervention. METHOD: With support from counties and a not-for
      profit managed care organization, CommonGround has been introduced in 10
      medication clinics, one Assertive Community Treatment (ACT) team, and one peer
      support center across Pennsylvania. Methods include analysis of data from the
      application's database and evaluation of health functioning, symptoms, and
      progress toward recovery. RESULTS: Health functioning improved over time and use
      of self-management strategies was associated with fewer concerns about medication
      side effects, fewer concerns about the impact of mental health medicine on
      physical health, more reports that mental health medicines were helping, and
      greater progress in individuals' recovery. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Using Personal Medicine empowers individuals to work with their
      prescribers to find a "right balance" between what they do to be well and what
      they take to be well. This program helps individuals and their service team focus
      on individual strengths and resilient self-care strategies. More research is
      needed to assess factors that may predict changes in outcomes and how a web-based
      tool focused on self-management strategies may moderate those factors.

PMID- 24320835
TI  - Implementation of illness management and recovery in the Veterans Administration:
      an on-line survey.
AB  - OBJECTIVE: This study explores the implementation of illness management and
      recovery (IMR) across Veterans Affairs Medical Centers (VAMCs). The
      implementation of illness management programming has been mandated in certain
      programs within VAMCs. IMR is consistent with the Department of Veteran Affairs
      (VA) emphasis on recovery-oriented, evidence-based treatments. This study
      examines both the penetration of IMR within the VA system and the barriers and
      facilitators to implementation. METHODS: An online survey was sent to local
      recovery coordinators, who, in turn, identified other local IMR experts. RESULTS:
      Respondents from 107 clinics (representing 101 VAMCs) answered the survey. Less
      than half of VAMCs provide IMR services. Psychosocial Rehabilitation and Recovery
      Centers (PRRC), which specialize in services for Veterans with psychiatric
      disabilities, are more likely to provide IMR; however, more than one third do
      not. Few respondents had access to IMR implementation tools such as training,
      consultation, or fidelity monitoring. Only about one fifth of IMR providers have
      been trained in IMR. Respondents reported several facilitators to implementation,
      such as knowledgeable staff members and peer support. Common barriers to
      implementation included limited staff availability and "intimidating" workbook
      materials. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The VA is well underway in
      its implementation of IMR; however, there is room for expansion. Implementation
      tools such as training and consultation are needed to ensure dissemination and
      quality within VA. Given the comparative resources and infrastructure of VA, it
      is likely that equal or greater implementation tools are necessary in other
      systems of care.

PMID- 24320836
TI  - Illness self-management for individuals in acute psychiatric care settings in
      Japan: cross-cultural adaptation of an American program.
AB  - OBJECTIVE: To examine whether the challenges of a cross-national adaptation of an
      American, evidence-based, illness self-management module for people with serious
      mental illnesses could be met. The UCLA Medication Management Module was adapted
      for use in Japan with individuals experiencing short-stay, acute care in an
      inpatient setting. METHOD: Two evaluations were conducted with 37 and 63 persons
      diagnosed as having schizophrenia and bipolar disorder, respectively, to test the
      feasibility and impact of the module as an intervention for illness self-
      management in an academic, Japanese psychiatric unit. RESULTS: The short-term
      feasibility was demonstrated by consumers' enhanced comprehension of the value
      and benefits of antipsychotic medication as well as their gaining positive,
      therapeutic attitudes toward use of medication. A second evaluation of the module
      revealed that consumers who participated in the skills training developed better
      understanding of the purposes of medication, more positive attitudes toward
      medication, and superior coping skills in dealing with medication side effects
      than their counterparts who received standard treatment. The greater benefits
      achieved from participating in the module persisted for 7 months postdischarge.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: While preliminary, these studies
      suggest the applicability of the Medication Management Module for illness
      management for Japanese hospital practice.

PMID- 24320838
TI  - The importance of fidelity in peer-based programs: the case of the Wellness
      Recovery Action Plan.
AB  - TOPIC: This article reflects on the importance of fidelity in the delivery of the
      peer-based Wellness Recovery Action Plan. PURPOSE: The purpose of this account is
      to describe efforts being made to preserve the evidenced-based practice of the
      Wellness Recovery Action Plan in ways that sustain the core value of self
      determination, maintain fidelity to its copyrighted curriculum, and support its
      positive impact for all people. SOURCES USED: The writing is based on personal
      knowledge and research literature related to the Wellness Recovery Action Plan.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The implementation and training of
      facilitators committed to the value of self-determination is critical to the
      fidelity of the evidence-based, peer-delivered Wellness Recovery Action Plan.
      Value-based training and WRAP standards are essential to ensure that WRAP
      continues to contribute substantially to transformative change.

PMID- 24320839
TI  - Personal narrative as a teaching tool.
AB  - Recovery-oriented service systems explicitly value including people with lived
      experiences of a mental and substance use diagnosis in the design, delivery, and
      evaluation of those services. Including first-person accounts as part of the
      education and training of service providers "demonstrates" recovery is possible,
      promotes empathy, offers insights into the lives of service users, and models a
      person-centered, person-first approach. More important, it serves as a visual and
      experiential example of the collegial relationships required for services that
      are truly recovery-oriented. This column provides recommendations for carefully
      planning in-person personal narratives as an effective teaching tool.

PMID- 24320837
TI  - Feasibility and effectiveness of an automated telehealth intervention to improve
      illness self-management in people with serious psychiatric and medical disorders.
AB  - OBJECTIVE: Effective monitoring and treatment are needed to address the elevated
      rates of medical comorbidity among individuals with serious mental illnesses.
      This study examined the feasibility and potential effectiveness of an automated
      telehealth intervention, supported by nurse health-care management, among adults
      with serious mental illnesses and chronic medical conditions. METHODS: We
      conducted a single-arm pilot trial with 70 individuals with serious mental
      illnesses and chronic medical conditions who were medically unstable (determined
      by treatment team or defined as multiple emergency room visits/hospitalizations
      within the past year). The telehealth intervention was delivered for 6 months
      with feasibility and acceptability as the primary outcomes. Measures of illness
      management self-efficacy, psychiatric symptoms, subjective health status, health
      indicators, and service use were also collected at baseline and at 6 months.
      RESULTS: Most individuals (n = 62; 89%) participated in at least 70% of the
      telehealth sessions. Participation was associated with improvements in self
      efficacy for managing depression and diastolic blood pressure. Almost all
      participants (n = 68; 98%) rated their understanding of their medical condition
      as "much better" or "somewhat better" postintervention. Among a subgroup of
      individuals with diabetes, decreases in fasting blood glucose were achieved, and
      among those with diabetes and major depression or bipolar disorder there were
      reductions in urgent care and primary care visits. CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: These results demonstrate the feasibility and acceptability of
      automated telehealth supported by a nurse care manager and the potential
      effectiveness of this technology in improving self-management of psychiatric
      symptoms and chronic health conditions among these high-risk individuals.

PMID- 24320840
TI  - Stereotyped beliefs about male and female OB-GYNS: relationship to provider
      choice and patient satisfaction.
AB  - BACKGROUND: Up to 60% of women prefer a female obstetrician-gynecologist (OB
      GYN), perhaps in part due to holding negative stereotypes of male providers.
      However, provider gender stereotypes have not been directly examined. The purpose
      of the current studies was to evaluate women's stereotypes of male and female OB
      GYN providers and the impact of these stereotypes on provider evaluations.
      METHODS: First, stereotypes of male and female OB-GYNs were elicited from 96
      undergraduate women who described the attributes and behaviors of a typical male
      or female OB-GYN. Next, 126 undergraduate women were randomized to review
      recordings depicting male or female OB-GYNs engaging in male or female-stereotype
      congruent behaviors during a well-woman visit. RESULTS: Participants overall had
      positive stereotypes of female OB-GYNs (e.g. knowledgeable, easy to talk to) but
      some negative stereotypes of males (e.g. unable to fully understand women's
      health issues). However, male and female OB-GYNs who engaged in female stereotype
      congruent behaviors were similarly preferred over providers who engaged in male
      stereotype congruent behavior. CONCLUSION: Women generally regard female OB-GYNs
      as highly competent, whereas some believe that being male is a disadvantage in
      providing OB-GYN care. However, providers who engage in behaviors associated with
      high quality care are evaluated positively, regardless of the provider's gender.

PMID- 24320841
TI  - Left ventricular systolic asynchrony: an important sign for cardiac involvement
      in plaque-type psoriasis.
AB  - Psoriasis is associated with cardiovascular diseases (CVD). The purpose of this
      study was to evaluate the relationship between Left Ventricular (LV) asynchrony
      and psoriasis. Asynchrony was assessed in 31 patients with psoriasis without
      evidence of CVD and 25 healthy subjects. All the patients and controls were
      subjected to tissue synchronization imaging (TSI), and conventional and tissue
      Doppler echocardiography. The time to regional peak systolic tissue velocity (Ts)
      in LV by the six-basal-six-midsegmental model was measured on ejection phase TSI
      images, and four TSI parameters of systolic asynchrony were computed. C-reactive
      protein (CRP) and erythrocyte sedimentation rate (ESR) levels in psoriatic
      patients were measured. All TSI parameters of LV asynchrony increased in
      psoriatic patients compared to the controls: the standard deviation (SD) of the
      12 LV segments Ts (37.3 +/- 14.8 vs. 24.6 +/- 11.1, P = 0.002); the maximal
      difference in Ts between any two of the 12 LV segments (112.7 +/- 39.8 vs. 83.1
      +/- 38.1, P = 0.01), the SD of the six basal LV segments (36.2 +/- 17.3 vs. 23.2
      +/- 14.5, P = 0.008); and the maximal difference in Ts between any two of the six
      basal LV segments (91.3 +/- 43.5 vs. 60.5 +/- 37.3, P = 0.01). LV asynchrony was
      observed in 67.7% of psoriatic patients. Higher CRP (1.9 +/- 1.3 vs. 0.92 +/-
      1.4, P = 0.04) and ESR (34.8 +/- 17.3 vs. 20 +/- 15.3, P = 0.03) levels were
      determined in patients with LV asynchrony. Regression analysis showed LV systolic
      asynchrony (P = 0.02), Tei index (P = 0.03), EF (P = 0.04), and E/A ratio (P =
      0.04) were independently associated with psoriasis. LV asynchrony firstly
      described in patients with psoriasis may be an important finding of cardiac
      involvement in psoriasis. 

PMID- 24320842
TI  - Imaging diagnosis-paraganglioma of the cauda equina: MR findings.
AB  - The magnetic resonance imaging features of a cauda equina paraganglioma in a 5
      year-old dog are described. Imaging revealed a well-defined, strongly contrast
      enhancing mass invading the adjacent vertebral body and infiltrating the
      intervertebral foramen bilaterally. Flow void, compatible with increased drainage
      veins around the mass, and macroscopically visible neovessels in contrast
      enhanced magnetic resonance angiography, as reported in numerous human studies,
      were not visible in this single case. The tumor recurred despite aggressive
      surgery and radiotherapy. This neoplasm should be considered in the differential
      diagnosis of cauda equina abnormalities in dogs. 

PMID- 24320843
TI  - Cold-induced rashes.

PMID- 24320845
TI  - Robust subspace discovery via relaxed rank minimization.
AB  - This letter examines the problem of robust subspace discovery from input data
      samples (instances) in the presence of overwhelming outliers and corruptions. A
      typical example is the case where we are given a set of images; each image
      contains, for example, a face at an unknown location of an unknown size; our goal
      is to identify or detect the face in the image and simultaneously learn its
      model. We employ a simple generative subspace model and propose a new formulation
      to simultaneously infer the label information and learn the model using low-rank
      optimization. Solving this problem enables us to simultaneously identify the
      ownership of instances to the subspace and learn the corresponding subspace
      model. We give an efficient and effective algorithm based on the alternating
      direction method of multipliers and provide extensive simulations and experiments
      to verify the effectiveness of our method. The proposed scheme can also be used
      to tackle many related high-dimensional combinatorial selection problems. 

PMID- 24320846
TI  - A parallel dual matrix method for blind signal separation.
AB  - A parallel dual matrix method that considers all cases of numerical relations
      between a mixing matrix and a separating matrix is proposed in this letter.
      Different constrained terms are used to construct cost function for every
      subalgorithm. These constrained terms reflect numerical relation. Therefore, a
      number of undesired solutions are excluded, the search region is reduced, and the
      convergence efficiency of the algorithm is ultimately improved. Moreover, any
      parallel subalgorithm is proven to converge to a desired separating matrix only
      if its cost function converges to zero. Computer simulations indicate that the
      algorithm efficiently performs blind signal separation. 

PMID- 24320844
TI  - Predictor of mortality in patients with amniotic fluid embolism.
AB  - AIM: The purpose of this study was to evaluate the possibility of establishing
      predictors of mortality in women with amniotic fluid embolism. METHODS: Our
      previous report identified eight factors associated with amniotic fluid embolism
      (AFE) fatality: dyspnea, cardiac arrest, loss of consciousness, serum sialyl Tn
      greater than 47 U/mL, serum interleukin-8 greater than 100 pg/mL, vaginal
      delivery, multiparity and term delivery. The ratio of the number of positive
      fatal factors to the number of possible fatal factors in the same case was
      calculated as the abundance ratio, which was used because information regarding
      all eight factors was not retrievable for all the patients at the time of
      registration. The patient group was divided into four quartiles based on this
      abundance ratio, and the mortality rate in each quartile was compared with the
      overall mortality rate among the 130 patients with AFE enrolled between 1992 and
      2006. The validity of this approach was confirmed in another dataset from a
      cohort of 38 patients with AFE in 2007. RESULTS: A statistically significant
      positive correlation was observed between the abundance ratio and the mortality
      in each quartile (P<0.01) for the patients with AFE enrolled between 1992 and
      2006. This result was also found in the AFE patients enrolled in 2007 (P<0.05).
      Thus, an increased in the abundance ratio of the eight fatal factors resulted in
      an increased case fatality rate. CONCLUSION: These data suggested that the
      abundance ratio of fatal factors may be a useful predictor of mortality and
      therefore may be expected to improve prognostic accuracy in the future.

PMID- 24320847
TI  - Approximate, computationally efficient online learning in Bayesian spiking
      neurons.
AB  - Bayesian spiking neurons (BSNs) provide a probabilistic interpretation of how
      neurons perform inference and learning. Online learning in BSNs typically
      involves parameter estimation based on maximum-likelihood expectation
      maximization (ML-EM) which is computationally slow and limits the potential of
      studying networks of BSNs. An online learning algorithm, fast learning (FL), is
      presented that is more computationally efficient than the benchmark ML-EM for a
      fixed number of time steps as the number of inputs to a BSN increases (e.g., 16.5
      times faster run times for 20 inputs). Although ML-EM appears to converge 2.0 to
      3.6 times faster than FL, the computational cost of ML-EM means that ML-EM takes
      longer to simulate to convergence than FL. FL also provides reasonable
      convergence performance that is robust to initialization of parameter estimates
      that are far from the true parameter values. However, parameter estimation
      depends on the range of true parameter values. Nevertheless, for a
      physiologically meaningful range of parameter values, FL gives very good average
      estimation accuracy, despite its approximate nature. The FL algorithm therefore
      provides an efficient tool, complementary to ML-EM, for exploring BSN networks in
      more detail in order to better understand their biological relevance. Moreover,
      the simplicity of the FL algorithm means it can be easily implemented in
      neuromorphic VLSI such that one can take advantage of the energy-efficient spike
      coding of BSNs. 

PMID- 24320848
TI  - Guaranteed classification via regularized similarity learning.
AB  - Learning an appropriate (dis)similarity function from the available data is a
      central problem in machine learning, since the success of many machine learning
      algorithms critically depends on the choice of a similarity function to compare
      examples. Despite many approaches to similarity metric learning that have been
      proposed, there has been little theoretical study on the links between similarity
      metric learning and the classification performance of the resulting classifier.
      In this letter, we propose a regularized similarity learning formulation
      associated with general matrix norms and establish their generalization bounds.
      We show that the generalization error of the resulting linear classifier can be
      bounded by the derived generalization bound of similarity learning. This shows
      that a good generalization of the learned similarity function guarantees a good
      classification of the resulting linear classifier. Our results extend and improve
      those obtained by Bellet, Habrard, and Sebban (2012). Due to the techniques
      dependent on the notion of uniform stability (Bousquet & Elisseeff, 2002), the
      bound obtained there holds true only for the Frobenius matrix-norm
      regularization. Our techniques using the Rademacher complexity (Bartlett &
      Mendelson, 2002) and its related Khinchin-type inequality enable us to establish
      bounds for regularized similarity learning formulations associated with general
      matrix norms, including sparse L1-norm and mixed (2,1)-norm.

PMID- 24320849
TI  - Noise-robust speech recognition through auditory feature detection and spike
      sequence decoding.
AB  - Speech recognition in noisy conditions is a major challenge for computer systems,
      but the human brain performs it routinely and accurately. Automatic speech
      recognition (ASR) systems that are inspired by neuroscience can potentially
      bridge the performance gap between humans and machines. We present a system for
      noise-robust isolated word recognition that works by decoding sequences of spikes
      from a population of simulated auditory feature-detecting neurons. Each neuron is
      trained to respond selectively to a brief spectrotemporal pattern, or feature,
      drawn from the simulated auditory nerve response to speech. The neural population
      conveys the time-dependent structure of a sound by its sequence of spikes. We
      compare two methods for decoding the spike sequences--one using a hidden Markov
      model-based recognizer, the other using a novel template-based recognition
      scheme. In the latter case, words are recognized by comparing their spike
      sequences to template sequences obtained from clean training data, using a
      similarity measure based on the length of the longest common sub-sequence. Using
      isolated spoken digits from the AURORA-2 database, we show that our combined
      system outperforms a state-of-the-art robust speech recognizer at low signal-to
      noise ratios. Both the spike-based encoding scheme and the template-based
      decoding offer gains in noise robustness over traditional speech recognition
      methods. Our system highlights potential advantages of spike-based acoustic
      coding and provides a biologically motivated framework for robust ASR
      development.

PMID- 24320850
TI  - Feature selection for ordinal text classification.
AB  - Ordinal classification (also known as ordinal regression) is a supervised
      learning task that consists of estimating the rating of a data item on a fixed,
      discrete rating scale. This problem is receiving increased attention from the
      sentiment analysis and opinion mining community due to the importance of
      automatically rating large amounts of product review data in digital form. As in
      other supervised learning tasks such as binary or multiclass classification,
      feature selection is often needed in order to improve efficiency and avoid
      overfitting. However, although feature selection has been extensively studied for
      other classification tasks, it has not for ordinal classification. In this
      letter, we present six novel feature selection methods that we have specifically
      devised for ordinal classification and test them on two data sets of product
      review data against three methods previously known from the literature, using two
      learning algorithms from the support vector regression tradition. The
      experimental results show that all six proposed metrics largely outperform all
      three baseline techniques (and are more stable than these others by an order of
      magnitude), on both data sets and for both learning algorithms. 

PMID- 24320851
TI  - Dopamine ramps are a consequence of reward prediction errors.
AB  - Temporal difference learning models of dopamine assert that phasic levels of
      dopamine encode a reward prediction error. However, this hypothesis has been
      challenged by recent observations of gradually ramping stratal dopamine levels as
      a goal is approached. This note describes conditions under which temporal
      difference learning models predict dopamine ramping. The key idea is
      representational: a quadratic transformation of proximity to the goal implies
      approximately linear ramping, as observed experimentally. 

PMID- 24320852
TI  - The ageing anaesthetist.

PMID- 24320853
TI  - The tiring anaesthetist.

PMID- 24320854
TI  - The ailing anaesthetist.

PMID- 24320855
TI  - Ultrasound-guided needle handling using a guidance positioning system in a
      phantom.
AB  - The SonixGPSTM needle guidance positioning system provides navigation assistance
      to facilitate needle handling during ultrasound-guided procedures. Each of 20
      inexperienced nurse anaesthetists performed 12 different ultrasound-guided tasks
      in a porcine phantom. Using both in-plane and out-of-plane approaches, they
      inserted a needle and made contact with metal rods at depths of 2, 4 and 6 cm. We
      compared their performances without and with navigation as paired observations.
      Using the out-of-plane approach, navigation yielded shorter execution times (26 s
      vs 14 s, respectively; p = 0.01) and fewer needle repositionings (8 vs 3,
      respectively; p = 0.001). Using the in-plane approach, the needle was more
      visible with navigation assistance: 24% vs 52% of execution time, respectively
      (95% CI: 44%-12%; p = 0.0025). Better needle visibility was associated with
      shorter execution times and fewer needle repositionings. Combining ultrasound
      guided techniques with the needle guidance positioning system may reduce tissue
      manipulation, thus improving patient comfort and safety.

PMID- 24320856
TI  - The analgesic efficiency of combined pregabalin and ketamine for total hip
      arthroplasty: a randomised, double-blind, controlled study.
AB  - Ketamine and pregabalin each provide postoperative analgesia, although the
      combination has yet to be evaluated. One hundred and forty-two patients
      undergoing total hip arthroplasty were randomly assigned to receive ketamine
      alone, pregabalin alone, ketamine and pregabalin combined, or placebo. Pain
      scores at rest and on movement, morphine consumption, side-effects, pressure pain
      thresholds and secondary hyperalgesia were evaluated. Mean (SD) total 48-h
      morphine use was reduced in patients given ketamine alone (52 (22) mg) and
      pregabalin alone (44 (20) mg) compared with placebo (77 (36) mg) p < 0.001.
      Morphine use was further reduced in patients given both ketamine and pregabalin
      (38 (19) mg) with an interaction between ketamine and pregabalin (ANOVA
      factorial; p = 0.028). Secondary hyperalgesia was reduced by ketamine. There were
      no differences between groups in pain scores after surgery, pressure pain
      thresholds or side-effects. The combination of pregabalin and ketamine has a
      small, beneficial clinical effect.

PMID- 24320857
TI  - An assessment of oropharyngeal airway position using a fibreoptic bronchoscope.
AB  - Selecting the appropriate oropharyngeal airway for safe and effective airway
      management is important in clinical practice. In this prospective observational
      study, we examined the position of the distal end of oropharyngeal airways using
      a fibreoptic bronchoscope. We enrolled 149 adults (72 men and 77 women). The
      correct airway size was determined by inserting four adult sizes Guedel airway
      (Hudson RCI; Teleflex Medical, Research Triangle, Park, NC, USA) (sizes 8, 9, 10
      and 11) sequentially in anaesthetised patients. The 'best fit' airway was size 10
      in 45 (62%) men, and size 9 in 58 (75%) women. However, when these airways were
      inserted, the distal end of the airway either touched or passed beyond the
      epiglottis tip in 20 (27%) men and six (8%) women, respectively. When a size-9
      airway was inserted in men and a size-8 airway inserted in women, the distal ends
      were obstructed by the tongue in three (2%) patients. In conclusion, a size-9
      airway in men and a size-8 airway in women are the most acceptable sizes for
      adults of average height. 

PMID- 24320858
TI  - Happy glove balloons.

PMID- 24320859
TI  - Isolated forearm technique and consciousness.

PMID- 24320860
TI  - A reply.

PMID- 24320861
TI  - Assessment of dental injury.

PMID- 24320862
TI  - Learning the 'traceback' approach for interscalene block.

PMID- 24320863
TI  - A reply.

PMID- 24320864
TI  - Intrapleural blocks for chest wall surgery.

PMID- 24320865
TI  - Pre-operative femoral nerve block vs fascia iliaca block for femoral neck
      fracture - a reply.

PMID- 24320866
TI  - Problems with saline flush for arterial lines.

PMID- 24320867
TI  - A reply.

PMID- 24320868
TI  - Contamination of arterial blood samples by flushing solution.

PMID- 24320869
TI  - Hypoglycaemia associated with the use of incorrect arterial flush solutions.

PMID- 24320870
TI  - Evidence for an unprecedented histidine hydroxyl modification on D2-His336 in
      Photosystem II of Thermosynechoccocus vulcanus and Thermosynechoccocus elongatus.
AB  - The electron density map of the 3D crystal of Photosystem II from
      Thermosynechococcus vulcanus with a 1.9 A resolution (PDB: 3ARC ) exhibits, in
      the two monomers in the asymmetric unit cell, an, until now, unidentified and
      uninterpreted strong difference in electron density centered at a distance of
      around 1.5 A from the nitrogen Ndelta of the imidazole ring of D2-His336. By
      MALDI-TOF/MS upon tryptic digestion, it is shown that ~20-30% of the fragments
      containing the D2-His336 residue of Photosystem II from both Thermosynechococcus
      vulcanus and Thermosynechococcus elongatus bear an extra mass of +16 Da. Such an
      extra mass likely corresponds to an unprecedented post-translational or chemical
      hydroxyl modification of histidine.

PMID- 24320871
TI  - Titania nanocoating on MnCO3 microspheres via liquid-phase deposition for
      fabrication of template-assisted core-shell- and hollow-structured composites.
AB  - A novel class of core-shell- and hollow-structured MnCO3/TiO2 composites was
      synthesized by titania nanocoating on MnCO3 microspheres via two-step liquid
      phase deposition at room temperature. Morphological change from core-shell to
      hollow microparticles was possible in the prepared samples by controlling
      prereaction time of MnCO3 and [NH4]2TiF6. Upon the prereaction process, the core
      of the core-shell MnCO3/TiO2 became highly porous, and a honeycomb-like surface
      that resembled the orientation of self-assembled MnCO3 nanocrystals was
      developed. The MnCO3 core was completely removed after 6 h prereaction.
      Calcination at 600  degrees C resulted in the transformation of both core-shell-
      and hollow-structured composites to Mn2O3/TiO2 anatase microspheres that retained
      their original morphologies. X-ray diffraction, field-emission scanning electron
      microscopy, Fourier transform infrared spectroscopy, transmission electron
      microscopy, and electron probe microanalysis were employed for microsphere
      characterization. As the first trial for application of the synthesized
      materials, solid-extraction of organics from aqueous media was examined using
      methylene blue (MB). Both types of Mn2O3/TiO2 composites showed very fast
      adsorption of MB with high extraction values of 5.2 and 6.4 MUmol g(-1) for the
      core-shell and hollow structures, respectively. Current work provides a new
      approach for facile fabrication of titania-metal oxide nanocomposites with unique
      morphological features and promising application possibilities. 

PMID- 24320872
TI  - Modeling complex metabolic reactions, ecological systems, and financial and legal
      networks with MIANN models based on Markov-Wiener node descriptors.
AB  - The use of numerical parameters in Complex Network analysis is expanding to new
      fields of application. At a molecular level, we can use them to describe the
      molecular structure of chemical entities, protein interactions, or metabolic
      networks. However, the applications are not restricted to the world of molecules
      and can be extended to the study of macroscopic nonliving systems, organisms, or
      even legal or social networks. On the other hand, the development of the field of
      Artificial Intelligence has led to the formulation of computational algorithms
      whose design is based on the structure and functioning of networks of biological
      neurons. These algorithms, called Artificial Neural Networks (ANNs), can be
      useful for the study of complex networks, since the numerical parameters that
      encode information of the network (for example centralities/node descriptors) can
      be used as inputs for the ANNs. The Wiener index (W) is a graph invariant widely
      used in chemoinformatics to quantify the molecular structure of drugs and to
      study complex networks. In this work, we explore for the first time the
      possibility of using Markov chains to calculate analogues of node distance
      numbers/W to describe complex networks from the point of view of their nodes.
      These parameters are called Markov-Wiener node descriptors of order k(th) (W(k)).
      Please, note that these descriptors are not related to Markov-Wiener stochastic
      processes. Here, we calculated the W(k)(i) values for a very high number of nodes
      (>100,000) in more than 100 different complex networks using the software MI
      NODES. These networks were grouped according to the field of application.
      Molecular networks include the Metabolic Reaction Networks (MRNs) of 40 different
      organisms. In addition, we analyzed other biological and legal and social
      networks. These include the Interaction Web Database Biological Networks
      (IWDBNs), with 75 food webs or ecological systems and the Spanish Financial Law
      Network (SFLN). The calculated W(k)(i) values were used as inputs for different
      ANNs in order to discriminate correct node connectivity patterns from incorrect
      random patterns. The MIANN models obtained present good values of
      Sensitivity/Specificity (%): MRNs (78/78), IWDBNs (90/88), and SFLN (86/84).
      These preliminary results are very promising from the point of view of a first
      exploratory study and suggest that the use of these models could be extended to
      the high-throughput re-evaluation of connectivity in known complex networks
      (collation).

PMID- 24320873
TI  - Arctic root-associated fungal community composition reflects environmental
      filtering.
AB  - There is growing evidence that root-associated fungi have important roles in
      Arctic ecosystems. Here, we assess the diversity of fungal communities associated
      with roots of the ectomycorrhizal perennial herb Bistorta vivipara on the Arctic
      archipelago of Svalbard and investigate whether spatial separation and
      bioclimatic variation are important structuring factors of fungal community
      composition. We sampled 160 plants of B. vivipara from 32 localities across
      Svalbard. DNA was extracted from entire root systems, and 454 pyrosequencing of
      ITS1 amplicons was used to profile the fungal communities. The fungal communities
      were predominantly composed of Basidiomycota (55% of reads) and Ascomycota (35%),
      with the orders Thelephorales (24%), Agaricales (13.8%), Pezizales (12.6%) and
      Sebacinales (11.3%) accounting for most of the reads. Plants from the same site
      or region had more similar fungal communities to one another than plants from
      other sites or regions, and sites clustered together along a weak latitudinal
      gradient. Furthermore, a decrease in per-plant OTU richness with increasing
      latitude was observed. However, no statistically significant spatial
      autocorrelation between sites was detected, suggesting that environmental
      filtering, not dispersal limitation, causes the observed patterns. Our analyses
      suggest that while latitudinal patterns in community composition and richness
      might reflect bioclimatic influences at global spatial scales, at the smaller
      spatial scale of the Svalbard archipelago, these changes more likely reflect
      varied bedrock composition and associated edaphic factors. The need for further
      studies focusing on identifying those specific bioclimatic and edaphic factors
      structuring root-associated fungal community composition at both global and local
      scales is emphasized.

PMID- 24320874
TI  - Active tunable absorption enhancement with graphene nanodisk arrays.
AB  - If not for its inherently weak optical absorption at visible and infrared
      wavelengths, graphene would show exceptional promise for optoelectronic
      applications. Here we show that by nanopatterning a graphene layer into an array
      of closely packed graphene nanodisks, its absorption efficiency can be increased
      from less than 3% to 30% in the infrared region of the spectrum. We examine the
      dependence of the enhanced absorption on nanodisk size and interparticle spacing.
      By incorporating graphene nanodisk arrays into an active device, we demonstrate
      that this enhanced absorption efficiency is voltage-tunable, indicating strong
      potential for nanopatterned graphene as an active medium for infrared electro
      optic devices. 

PMID- 24320875
TI  - Growth factor and proteinase profile of Vivostat(r) platelet-rich fibrin linked
      to tissue repair.
AB  - BACKGROUND AND OBJECTIVES: Autologous platelet-rich fibrin (PRF((r))) is prepared
      by the automatic Vivostat((r)) system. Conflicting results with Vivostat PRF in
      acute wound healing prompted us to examine its cellular and biomolecular
      composition. Specifically, platelets, selected growth factors and matrix
      metalloproteinase (MMP)-9 were quantified using novel analytical methods.
      MATERIALS AND METHODS: Ten healthy non-thrombocytopenic volunteers donated blood
      for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood
      and serum procured in parallel served as baseline controls. Leucocyte,
      erythrocyte and platelet counts in whole blood and fibrin-I were determined by
      automated haematology analyser. Platelet concentration in PRF was quantified
      manually by stereologic analysis of Giemsa-stained tissue sections, and the total
      content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays.
      RESULTS: The number of leucocytes and erythrocytes was reduced (P < 0.001),
      whereas platelets increased (P < 0.001) in fibrin-I versus whole blood. PRF
      contained 982 +/- 206 * 10(9) platelets/l representing 3.9-fold (P < 0.001)
      enrichment relative to whole blood. Growth factor abundance in Vivostat PRF and
      serum was in descending order: transforming growth factor-beta1 [5.1-fold higher
      in PRF than serum, P < 0.001] > platelet-derived growth factor (PDGF)-AB [2.5
      fold, P < 0.01] > PDGF-BB [1.6-fold, P < 0.05] > vascular endothelial growth
      factor > basic fibroblast growth factor [75-fold, P < 0.001]. MMP-9 was reduced
      139-fold (P < 0.001) compared with serum, reflecting leucocyte depletion in PRF.
      CONCLUSION: The gained knowledge on platelet enrichment and biomolecular
      constituents may guide clinicians in their optimal use of Vivostat PRF for tissue
      regenerative applications.

PMID- 24320876
TI  - Resin glycosides from Porana duclouxii.
AB  - A new intact resin glycoside (3) and two glycosidic acids (1 and 2), all having a
      common trisaccharide moiety and (11S)-hydroxytetradecanoic acid or (3S,11S)
      dihydroxytetradecanoic acid as the aglycone, were obtained from the roots of
      Porana duclouxii. Their structures were elucidated by spectroscopic analyses and
      chemical correlations. These compounds represent the first examples of resin
      glycosides from the genus Porana. 

PMID- 24320877
TI  - Retinal ganglion cell distribution and visual acuity in alpacas (Vicugna pacos).
AB  - OBJECTIVE: To investigate the distribution of retinal ganglion cells (RGCs) and
      visual acuity in alpacas (Vicugna pacos) through Brn-3a immunofluorescent
      labeling. PROCEDURES: Five eyes from four healthy alpacas with normal ophthalmic
      examination findings were included in the study. The axial length of the globes
      was measured before fixation. All five retinas were treated with Brn-3a
      antibodies to label RGCs. Images taken with a fluorescent microscope were used
      for RGC counting. RGC density maps were reconstructed by computer software.
      Visual acuity was estimated based on the results of peak RGC density and ocular
      anatomical parameters. RESULTS: The reconstructed retinal maps from Brn-3a
      labeling showed a horizontal streak across the retinal meridian superior to the
      optic nerve head with a temporal, upward extension. The highest RGC densities
      were in the temporal retinas. The maximal visual acuity was located in the
      temporal retina and was estimated to range between 12.5 and 13.4 cycles per
      degree. CONCLUSIONS: Alpacas have a horizontal streak across the retinal meridian
      superior to the optic disk with a temporal, upward extension based on the Brn-3a
      labeling of RGCs. The maximal visual acuity was located in the temporal retina.
      The reconstructed retinal maps indicate the RGC topography of alpacas is similar
      to that of other herbivores, but is different from that of dromedary camels.

PMID- 24320878
TI  - 68Ga-labeled gold glyconanoparticles for exploring blood-brain barrier
      permeability: preparation, biodistribution studies, and improved brain uptake via
      neuropeptide conjugation.
AB  - New tools and techniques to improve brain visualization and assess drug
      permeability across the blood-brain barrier (BBB) are critically needed. Positron
      emission tomography (PET) is a highly sensitive, noninvasive technique that
      allows the evaluation of the BBB permeability under normal and disease-state
      conditions. In this work, we have developed the synthesis of novel water-soluble
      and biocompatible glucose-coated gold nanoparticles (GNPs) carrying BBB-permeable
      neuropeptides and a chelator of the positron emitter (68)Ga as a PET reporter for
      in vivo tracking biodistribution. The small GNPs (2 nm) are stabilized and
      solubilized by a glucose conjugate. A NOTA ligand is the chelating agent for the
      (68)Ga, and two related opioid peptides are used as targeting ligands for
      improving BBB crossing. The radioactive labeling of the GNPs is completed in 30
      min at 70  degrees C followed by purification via centrifugal filtration. As a
      proof of principle, a biodistribution study in rats is performed for the
      different (68)Ga-GNPs. The accumulation of radioactivity in different organs
      after intravenous administration is measured by whole body PET imaging and gamma
      counter measurements of selected organs. The biodistribution of the (68)Ga-GNPs
      varies depending on the ligands, as GNPs with the same gold core size show
      different distribution profiles. One of the targeted (68)Ga-GNPs improves BBB
      crossing near 3-fold (0.020 +/- 0.0050% ID/g) compared to nontargeted GNPs
      (0.0073 +/- 0.0024% ID/g) as measured by dissection and tissue counting. 

PMID- 24320880
TI  - Sustained-release pellets of nifedipine using microcrystals combined with MCC
      based matrix.
AB  - The purpose of this study was to prepare sustained-release pellets of nifedipine
      (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques
      were employed to prepare the microcrystals and pellets, respectively. The drug
      release mechanism and the influencing factors were investigated. After milled
      with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM)
      was 5 MUm, which is 15-fold smaller than that of raw material. DSC, X-ray powder
      diffraction and microscopic observation confirmed the microcrystals of drug were
      maintained in the CGM. With increased milling time and the content of HPMC, the
      dissolution rate was greatly enhanced compared with the raw material. The NSPs
      prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5%
      HPMC solution for 210 min, exhibited sustained release pattern within 8 h.
      Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely
      related to the microstructure of pellet. High stability of NSPs was confirmed
      after 6 months of accelerated stability test. Using commercially available
      sustained product as reference, bioequivalence study in beagle dogs was executed
      and two formulations were bioequivalent. This sustained release pellet
      formulation of nifedipine was advantageous with convenient and easy scaled-up
      preparation process.

PMID- 24320879
TI  - Low-oxygen culture conditions extend the multipotent properties of human retinal
      progenitor cells.
AB  - PURPOSE: Development of an effective cell-based therapy is highly dependent upon
      having a reproducible cell source suitable for transplantation. One potential
      source, isolated from the developing fetal neural retina, is the human retinal
      progenitor cell (hRPC). One limiting factor for the use of hRPCs is their in
      vitro expansion limit. As such, the aim of this study was to determine whether
      culturing hRPCs under 3% O2 would support their proliferative capacity while
      maintaining multipotency. METHODS: To determine the effect of low oxygen on the
      ability of hRPCs to self-renew, rates of proliferation and apoptosis, telomerase
      activity, and expression of proliferative, stemness, and differentiation markers
      were assessed for hRPCs cultured in 3% and 20% oxygen conditions. RESULTS:
      Culture under 3% oxygen increases the proliferation rate and shifts the
      proliferation limit of hRPCs to greater 40 divisions. This increased capacity for
      proliferation is correlated with an upregulation of Ki67, CyclinD1, and
      telomerase activity and a decrease in p53 expression and apoptosis. Increased
      expression of cMyc, Klf4, Oct4, and Sox2 in 3% O2 is correlated with
      stabilization of both HIF1alpha and HIF2alpha. The eye field development markers
      Pax6, Sox2, and Otx2 are present in hRPCs up to passage 16 in 3% O2 . Following
      in vitro differentiation hRPCs expanded in the 3% O2 were able to generate
      specialized retinal cells, including rods and cones. CONCLUSIONS: Low-oxygen
      culture conditions act to maintain both multipotency and self-renewal properties
      of hRPCs in vitro. The extended expansion limits permit the development of a
      clinical-grade reagent for transplantation.

PMID- 24320881
TI  - Feasibility of poly (epsilon-caprolactone-co-DL-lactide) as a biodegradable
      material for in situ forming implants: evaluation of drug release and in vivo
      degradation.
AB  - The purpose of this study was to evaluate the technical feasibility of poly
      (epsilon-caprolactone-co-DL-lactide), P (CL/DL-LA), for injectable in situ
      forming implants (ISFI). The ISFI was prepared by dissolving P (CL/DL-LA) in N
      methyl-2-pyrrolidone (NMP), and Testosterone undecanoate (TU) was used as model
      drug. The effect of various polymer concentrations, molecular weights (Mws) and
      drug loads on the drug release from the TU-loaded ISFI systems was investigated
      in vitro. The release of TU-loaded ISFI was also evaluated in rats. In addition,
      a subcutaneous rabbit model was used to evaluate the degradation and foreign-body
      reaction of P (CL/DL-LA) ISFI. The use of higher concentration of P (CL/DL-LA)
      with higher molecule weight and larger CL:DL-LA monomer ratio for the TU-loaded
      ISFI gave a slower drug release. The ISFI of 80/20 P (CL/DL-LA) (Mw 61 753):NMP
      20:80 with 16% TU formulation increased serum testosterone levels in rats over a
      period of three months. The in vivo degradation and biocompatibility study of
      ISFI shows that P (CL/DL-LA) degrades by a process of bulk degradation and that
      the foreign-body reaction of this biomaterial is relatively mild. In summary, our
      investigations demonstrate that in situ parenteral drug delivery systems can be
      obtained from P (CL/DL-LA) solutions.

PMID- 24320882
TI  - Global analysis of cis-natural antisense transcripts and their heat-responsive
      nat-siRNAs in Brassica rapa.
AB  - BACKGROUND: Brassica rapa includes several important leaf vegetable crops whose
      production is often damaged by high temperature. Cis-natural antisense
      transcripts (cis-NATs) and cis-NATs-derived small interfering RNAs (nat-siRNAs)
      play important roles in plant development and stress responses. However, genome
      wide cis-NATs in B. rapa are not known. The NATs and nat-siRNAs that respond to
      heat stress have never been well studied in B. rapa. Here, we took advantage of
      RNA-seq and small RNA (sRNA) deep sequencing technology to identify cis-NATs and
      heat responsive nat-siRNAs in B. rapa. RESULTS: Analyses of four RNA sequencing
      datasets revealed 1031 cis-NATs B. rapa ssp. chinensis cv Wut and B. rapa ssp.
      pekinensis cv. Bre. Based on sequence homology between Arabidopsis thaliana and
      B. rapa, 303 conserved cis-NATs in B. rapa were found to correspond to 280 cis
      NATs in Arabidopsis; the remaining 728 novel cis-NATs were identified as Brassica
      specific ones. Using six sRNA libraries, 4846 nat-siRNAs derived from 150 cis
      NATs were detected. Differential expression analysis revealed that nat-siRNAs
      derived from 12 cis-NATs were responsive to heat stress, and most of them showed
      strand bias. Real-time PCR indicated that most of the transcripts generating heat
      responsive nat-siRNAs were upregulated under heat stress, while the transcripts
      from the opposite strands of the same loci were downregulated. CONCLUSIONS: Our
      results provide the first subsets of genome-wide cis-NATs and heat-responsive nat
      siRNAs in B. rapa; these sRNAs are potentially useful for the genetic improvement
      of heat tolerance in B. rapa and other crops.

PMID- 24320884
TI  - The metabolic fate of [14C]-fenclozic acid in the hepatic reductase null (HRN)
      mouse.
AB  - 1. The distribution, metabolism, excretion and hepatic effects of fenclozic acid
      were investigated following a single oral dose of 10 mg/kg to hepatic reductase
      null (HRN) mice. 2. The majority of the [(14)C]-fenclozic acid was eliminated via
      the urine/aqueous cage wash, (55%) with a smaller portion excreted in the faeces,
      (5%). The total recovery of radioactivity in the excreta over the 72 h period
      studied was ca. 60%. 3. Metabolism of fenclozic acid in the HRN mice was entirely
      to the carboxylic acid function and was dominated by amino acid conjugation to
      glycine and taurine, with lesser amounts of an acyl glucuronide. 4. Whole body
      autoradiography of mice showed general distribution into all tissues except the
      brain. Radioactivity was still detectable in the kidney and liver of the HRN mice
      at 72 h post-dose. Covalent binding studies showed evidence of binding to kidney,
      liver and plasma proteins however, the degree of binding was less than 50 pmol
      equiv/mg protein for all tissues. 5. The HRN mouse appears to be a useful in vivo
      model for the study of the Phase II conjugation metabolism of fenclozic acid in
      the absence of hepatic cytochrome P450-related oxidative metabolism.

PMID- 24320885
TI  - Chimeric rodents with humanized liver: bridging the preclinical/clinical trial
      gap in ADME/toxicity studies.
AB  - 1. Immunocompromised mice with humanized livers were developed in the mid-1990s
      to allow the study of human hepatotropic viruses, which normally replicate only
      in higher primates. The production of the uPA/SCID mouse was the vanguard of
      these models and remains the most widely worked upon model for an ever increasing
      range of applications. 2. Since toxicology is conducted in laboratory animal
      species with the implicit intent of predicting the outcome of accidental, or
      intentional, human exposure, the potential for using an in vivo model with a
      humanised metabolism opens up the possibility of better predicting the human
      response following exposure to drugs and industrial chemicals. Chimeric humanised
      mice provide the tool for bridging between the non-clinical laboratory safety and
      metabolism studies, carried out in rodent and non-rodent species, and the first
      in man clinical trials. 3. Chimeric mice carrying a human liver have now been
      validated against a wide range of different drugs and chemical classes, and have
      been shown to clearly differentiate metabolically from the recipient mouse, and
      to show metabolic pathways more similar to those expected from human liver. 4.
      This review critically appraises the available animal models carrying human
      livers and where future developments would improve the existing systems.

PMID- 24320886
TI  - Controlled seeding of laser deposited Ta:TiO2 nanobrushes and their performance
      as photoanode for dye sensitized solar cells.
AB  - Hexagonal patterned indium tin oxide (ITO) with a height of 1.5 MUm was
      fabricated on fluorinated SnO2 (FTO) substrate via nanoimprint lithography and
      pulsed laser deposition (PLD). Tantalum doped TiO2 was deposited on the patterned
      substrate by PLD. The film of Ta:TiO2 grew vertically and separately on the
      patterned ITO and formed a brush-like structure. Dye-sensitized solar cells with
      the Ta:TiO2 film deposited on the patterned substrate as well as flat FTO
      substrate for comparison were fabricated and tested. The device with the
      patterned substrate showed a 25% increase in short circuit current (Jsc) compared
      to the one with flat FTO substrate. Optical and photoelectrochemical
      characterization techniques were performed to investigate the improvement. The
      increase of Jsc was attributed to the enhancements of light absorption in the 600
      750 nm range and collection of excited electrons by the brush-like structure and
      the patterned ITO, respectively. 

PMID- 24320887
TI  - Experience of care home residents with Parkinson's disease: Reason for admission
      and service use.
AB  - AIM: The care needs of people with Parkinson's disease (PD) are poorly
      understood. We aimed to investigate the factors that precipitate entry to
      institutional care, and on-going care needs once in care, within a representative
      cohort of community-dwelling people with PD. METHOD: All people with idiopathic
      PD, Parkinson's plus syndromes and vascular parkinsonism under the care of the
      Northumbria Healthcare NHS Foundation Trust PD service who were living in care
      homes on 1 January 2013 were included. Disease severity (Hoehn and Yahr stage)
      and demographic data were collected. Admissions to hospital over the previous 2
      years and in the year before institutional care admission were documented.
      RESULTS: A total of 90 patients (51 females) with a mean age of 81.3 years were
      included. During care home stay, the median number of emergency department
      attendances, the median number of hospital admissions and the median length of
      stay for those admitted per year were significantly lower than before care home
      admission. Both before care home admission and during care home stay, falls were
      the most common diagnoses in people attending emergency departments, with 32 of
      65 (49.2%) admissions before and 34 of 59 (57.6%) admissions during care home
      stay having falls recorded as a cause of attendance. CONCLUSIONS: Hospital
      attendances and admissions were relatively common, even after institutional care
      home placement. Events precipitating admission, such as falls, might be
      preventable. PD nurse specialists could be an effective way to help train staff
      in homes where someone is known to have PD.

PMID- 24320888
TI  - Annual review issue: soft tissue tumour pathology.

PMID- 24320889
TI  - The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review.
AB  - Many soft tissue sarcomas have chromosomal translocations with resultant
      formation of new fusion genes. Among the genes that can be rearranged, the EWSR1
      gene has been identified as a partner in a wide variety of clinically and
      pathologically diverse sarcomas as well as some non-mesenchymal tumours. The
      former include Ewing sarcoma and similar (Ewing-like) small round cell sarcomas,
      desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid
      chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft
      tissue and clear cell sarcoma-like tumours of the gastrointestinal tract, primary
      pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic
      examples of low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma
      and mesothelioma. EWSR1 is a 'promiscuous' gene that can fuse with many different
      partner genes, but sometimes this results in phenotypically identical tumours.
      EWSR1 can, conversely, partner with the same genes in morphologically and
      behaviourally different neoplasms. This paper reviews the diversity of the
      several soft tissue tumour types that are associated with rearrangement of the
      EWSR1 gene. 

PMID- 24320890
TI  - Evolving techniques for gene fusion detection in soft tissue tumours.
AB  - Chromosomal rearrangements resulting in the fusion of coding parts from two genes
      or in the exchange of regulatory sequences are present in approximately 20% of
      all human neoplasms. More than 1000 such gene fusions have now been described,
      with close to 100 of them in soft tissue tumours. Although little is still known
      about the functional outcome of many of these gene fusions, it is well
      established that most of them have a major impact on tumorigenesis. Furthermore,
      the strong association between type of gene fusion and morphological subtype
      makes them highly useful diagnostic markers. Until recently, the vast majority of
      gene fusions were identified through molecular cytogenetic characterization of
      rearrangements detected at chromosome banding analysis, followed by use of the
      reverse transcriptase-polymerase chain reaction (RT-PCR) and Sanger sequencing.
      With the advent of next-generation sequencing (NGS) technologies, notably of
      whole transcriptomes or all poly-A(+) mRNA molecules, the possibility of
      detecting new gene fusions has increased dramatically. Already, a large number of
      novel gene fusions have been identified through NGS approaches and it can be
      predicted that these technologies soon will become standard diagnostic clinical
      tools. 

PMID- 24320891
TI  - Direct thiol-ene photocoating of polyorganosiloxane microparticles.
AB  - This work presents the modification of polyorganosiloxane microparticles by
      surface-initiated thiol-ene photochemistry. By this photocoating, we prepared
      different core/shell particles with a polymeric shell within narrow size
      distributions (PDI = 0.041-0.12). As core particle, we used highly monodisperse
      spherical polyorganosiloxane particles prepared from (3
      mercaptopropyl)trimethoxysilane (MPTMS) with a radius of 0.49 MUm. We utilize the
      high surface coverage of mercaptopropyl functions to generate surface-localized
      radicals upon irradiation with UVA-light without additional photoinitiator. The
      continuous generation of radicals was followed by a dye degradation experiment
      (UV/vis spectroscopy). Surface-localized radicals were used as copolymer
      anchoring sites ("grafting-onto" deposition of different PB-b-PS diblock
      copolymers) and polymerization initiators ("grafting-from" polymerization of PS).
      Photocoated particles were characterized for their morphology (SEM, TEM), size,
      and size distribution (DLS). For PS-coated particles, the polymer content (up to
      24% in 24 h) was controlled by the polymerization time upon UVA exposure. The
      coating thickness was evaluated by thermogravimetric analysis (TGA) using a
      simple analytical core/shell model. Raman spectroscopy was applied to directly
      follow the time-dependent consumption of thiols by photoinitiation. 

PMID- 24320892
TI  - Exploring beta-hydroxy gamma-amino acids (statines) in the design of hybrid
      peptide foldamers.
AB  - The synthesis and characterization of syn and anti beta-hydroxy gamma-amino acid
      (statine) diastereoisomers, their utilization in the design of hybrid peptide
      foldamers, and their single crystal conformations are studied. 

PMID- 24320893
TI  - The technology revolution is here - are you prepared for it?

PMID- 24320894
TI  - Management of fear and anxiety in the dental clinic: a review.
AB  - People who are highly anxious about undergoing dental treatment comprise
      approximately one in seven of the population and require careful and considerate
      management by dental practitioners. This paper presents a review of a number of
      non-pharmacological (behavioural and cognitive) techniques that can be used in
      the dental clinic or surgery in order to assist anxious individuals obtain needed
      dental care. Practical advice for managing anxious patients is provided and the
      evidence base for the various approaches is examined and summarized. The
      importance of firstly identifying dental fear and then understanding its
      aetiology, nature and associated components is stressed. Anxiety management
      techniques range from good communication and establishing rapport to the use of
      systematic desensitization and hypnosis. Some techniques require specialist
      training but many others could usefully be adopted for all dental patients,
      regardless of their known level of dental anxiety. It is concluded that
      successfully managing dentally fearful individuals is achievable for clinicians
      but requires a greater level of understanding, good communication and a phased
      treatment approach. There is an acceptable evidence base for several non
      pharmacological anxiety management practices to help augment dental practitioners
      providing care to anxious or fearful children and adults. 

PMID- 24320895
TI  - Clinical guidelines for oral appliance therapy in the treatment of snoring and
      obstructive sleep apnoea.
AB  - The purpose of this review is to provide guidelines for the use of oral
      appliances (OAs) for the treatment of snoring and obstructive sleep apnoea (OSA)
      in Australia. A review of the scientific literature up to June 2012 regarding the
      clinical use of OAs in the treatment of snoring and OSA was undertaken by a
      dental and medical sleep specialists team consisting of respiratory sleep
      physicians, an otolaryngologist, orthodontist, oral and maxillofacial surgeon and
      an oral medicine specialist. The recommendations are based on the most recent
      evidence from studies obtained from peer reviewed literature. Oral appliances can
      be an effective therapeutic option for the treatment of snoring and OSA across a
      broad range of disease severity. However, the response to therapy is variable.
      While a significant proportion of subjects have a near complete control of the
      apnoea and snoring when using an OA, a significant proportion do not respond, and
      others show a partial response. Measurements of baseline and treatment success
      should ideally be undertaken. A coordinated team approach between medical
      practitioner and dentist should be fostered to enhance treatment outcomes.
      Ongoing patient follow-up to monitor treatment efficacy, OA comfort and side
      effects are cardinal to long-term treatment success and OA compliance. 

PMID- 24320896
TI  - Maxillary implant overdentures: current controversies.
AB  - Mandibular implant overdentures have established and predictable benefits over
      traditional mucosa-borne mandibular dentures and now form part of mainstream
      dentistry. Maxillary implant overdentures present a number of different
      challenges. This selective review highlights the paucity of evidence and
      inconsistent findings in the maxillary implant overdenture literature. 

PMID- 24320897
TI  - Cervicofacial subcutaneous emphysema associated with dental laser treatment.
AB  - Cervicofacial subcutaneous emphysema is a rare complication of dental procedures.
      Although most cases of emphysema occur incidentally with the use of a high-speed
      air turbine handpiece, there have been some reports over the past decade of cases
      caused by dental laser treatment. Emphysema as a complication caused by the air
      cooling spray of a dental laser is not well known, even though dental lasers
      utilize compressed air just as air turbines and syringes do. In this study, we
      comprehensively reviewed cases of emphysema attributed to dental laser treatment
      that appeared in the literature between January 2001 and September 2012, and we
      included three such cases referred to us. Among 13 cases identified in total,
      nine had cervicofacial subcutaneous and mediastinal emphysema. Compared with past
      reviews, the incidence of mediastinal emphysema caused by dental laser treatment
      was higher than emphysema caused by dental procedure without dental laser use.
      Eight patients underwent CO2 laser treatment and two underwent Er:YAG laser
      treatment. Nine patients had emphysema following laser irradiation for soft
      tissue incision. Dentists and oral surgeons should be cognizant of the potential
      risk for iatrogenic emphysema caused by the air cooling spray during dental laser
      treatment and ensure proper usage of lasers. 

PMID- 24320899
TI  - The all-ceramic, inlay supported fixed partial denture. Part 5. Extended finite
      element analysis validation.
AB  - BACKGROUND: This study is the last in a series detailing an investigation into
      the all-ceramic, inlay supported fixed partial denture, the major concern of
      which has been the examination of the stress responses of the bridge via the use
      of finite element analysis (FEA) and its validation. The progression from a
      classic FEA to the current extended or enriched FEA (XFEA) will be described and
      the validation performed. METHODS: XFEA modelling was compared and validated
      against the experimental model analysis (EMA) as described in a previous study.
      RESULTS: The two EMA load case fracture strengths of 160 N and 313 N compared
      favourably with the best two fracture predictions from the XFEA of 185 N and 213
      N (maximum principal stress criterion) respectively, with the origin of fracture
      and overall trajectory and pattern of crack propagation agreeing very well.
      CONCLUSIONS: XFEA load prediction is within 15% of the EMA in the best case. The
      sensitivity of the bridges to loading position variations was accurately
      predicted by the XFEA, together with the change in fracture origin from the molar
      to premolar embrasures. With this, the authors believe that they have provided a
      convincing validation, both qualitatively and quantitatively, of an anatomically
      realistic dental bridge.

PMID- 24320898
TI  - Assessment of residual active chlorine in sodium hypochlorite solutions after
      dissolution of porcine incisor pulpal tissue.
AB  - BACKGROUND: In previous studies, surfactant-containing Hypochlor brands of sodium
      hypochlorite showed better tissue solubilizing abilities than Milton; differences
      not explained by original active chlorine content or presence of surfactant. It
      was postulated that exhaustion of active chlorine content could explain
      differences. This study aimed to assess whether Milton's poorer performance was
      due to exhaustion of active chlorine. Parallel experiments assessed the influence
      of titration methods, and the presence of chlorates, on active chlorine
      measurements. METHODS: Time required to dissolve one or groups of 10 samples of
      porcine incisor pulp samples in Milton was determined. Residual active chlorine
      was assessed by thermometric titration. Iodometric and thermometric titration was
      carried out on samples of Milton. Chlorate content was also measured. RESULTS:
      Dissolution of single and 10 pulp samples caused a mean loss of 1% and 3%
      respectively of active chlorine, not being proportional to tissue dissolved.
      Thermometric ammonium ion titration resulted in 10% lower values than iodometric
      titration. Chlorate accounted for much of this difference. CONCLUSIONS: Depletion
      of active chlorine is not the reason for differences in tissue dissolving
      capabilities of Milton. Thermometric ammonium ion titration gives more accurate
      measurement of active chlorine content than iodometric titration.

PMID- 24320900
TI  - Reduction in prevalence of Archaea after periodontal therapy in subjects with
      generalized aggressive periodontitis.
AB  - BACKGROUND: There is evidence of a possible relationship between Archaea and
      periodontal disease; however, to date few studies have assessed the changes in
      prevalence of this domain after periodontal therapy. The aim of this randomized
      double-blind and placebo-controlled study was to assess if periodontal treatment
      with or without systemic antibiotic would change the prevalence of Archaea after
      periodontal therapy. METHODS: Thirty subjects were randomly assigned to receive
      scaling and root planing (SRP) alone or combined with metronidazole (MTZ) +
      amoxicillin (AMX) for 14 days. Clinical and microbiological examinations were
      performed at baseline and at six months post-SRP. Nine subgingival plaque samples
      per subject were analysed for the presence of Archaea. RESULTS: SRP alone or
      combined with MTZ + AMX significantly reduced the prevalence of subjects
      colonized by Archaea at six months post-therapy. However, no significant
      differences between treatment groups were observed (p > 0.05). Both therapies led
      to a statistically significant decrease in the mean percentage of sites colonized
      by Archaea (p < 0.05). A negative Spearman correlation was observed between the
      presence of Archaea and the mean clinical attachment gain at six months post
      therapy (r(2) = -0.61; 95% CI -0.80- -0.31; p = 0.003). CONCLUSIONS: SRP alone or
      combined with MTZ + AMX provides a similar reduction in the prevalence of Archaea
      in the subgingival biofilm of subjects with generalized aggressive periodontitis.

PMID- 24320901
TI  - Effect of G-Coat Plus on the mechanical properties of glass-ionomer cements.
AB  - BACKGROUND: Although various mechanical properties of tooth-coloured materials
      have been described, little data have been published on the effect of ageing and
      G-Coat Plus on the hardness and strength of the glass-ionomer cements (GICs).
      METHODS: Specimens were prepared from one polyacid-modified resin composite
      (PAMRC; Freedom, SDI), one resin-modified glass-ionomer cement; (RM-GIC; Fuji II
      LC, GC), and one conventional glass-ionomer cement; (GIC; Fuji IX, GC). GIC and
      RM-GIC were tested both with and without applying G-Coat Plus (GC). Specimens
      were conditioned in 37  degrees C distilled water for either 24 hours, four and
      eight weeks. Half the specimens were subjected to a shear punch test using a
      universal testing machine; the remaining half was subjected to Vickers Hardness
      test. RESULTS: Data analysis showed that the hardness and shear punch values were
      material dependent. The hardness and shear punch of the PAMRC was the highest and
      GIC the lowest. Applying the G-Coat Plus was associated with a significant
      decrease in the hardness of the materials but increase in the shear punch
      strength after four and eight weeks. CONCLUSIONS: The mechanical properties of
      the restorative materials were affected by applying G-Coat Plus and distilled
      water immersion over time. The PAMRC was significantly stronger and harder than
      the RM-GIC or GIC.

PMID- 24320902
TI  - The effect of caries excavation methods on the bond strength of etch-and-rinse
      and self-etch adhesives to caries affected dentine.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of
      chemomechanical caries removal and conventional caries excavation on the
      microtensile bond strength of three different dentine adhesive systems. METHODS:
      Thirty extracted human mandibular molars with radiographic signs of dental caries
      extending up to the middle third of dentine were sectioned longitudinally through
      the centre of the carious lesion in a buccolingual direction to yield two
      sections. One half of each tooth was excavated by tungsten carbide bur and the
      other half was chemomechanically treated with Carisolv((r)) . Three dentine
      bonding systems: an etch-and-rinse single bottle adhesive (Single Bond, 3M ESPE);
      a two bottle, two-step self-etch bonding system (One Coat Self Etching Bond,
      Coltene Whaledent); and a single-step, single bottle self-etch adhesive (Adper
      Easy Bond Self-Etch Adhesive, 3M ESPE) were applied and composite build-up was
      done. The specimens were tested for microtensile bond strength. Data were
      analysed using two-way analysis of variance and pair-wise multiple comparisons
      were done using the Holm-Sidak method. RESULTS: The etch-and-rinse adhesive and
      two bottle self-etch system showed significantly higher bond strength than the
      single bottle self-etch system. Caries excavation method had no influence on bond
      strength values. CONCLUSIONS: Carisolv((r)) did not affect the microtensile bond
      strength values of different adhesive systems tested to the caries affected
      dentine.

PMID- 24320903
TI  - Micro-computerized tomography assessment of fluorescence aided caries excavation
      (FACE) technology: comparison with three other caries removal techniques.
AB  - BACKGROUND: The aim of this study was to determine the caries removal
      effectiveness (CRE) and minimal invasiveness potential (MIP) of four dentine
      caries removal methods. METHODS: After carious molars were scanned using micro
      computerized tomography (micro-CT), dentine caries were removed by fluorescence
      aided caries excavation (FACE) technology, laser induced fluorescence (LIF),
      chemomechanical excavation (CME), and conventional excavation (CE). Micro-CT was
      then repeated. CRE was determined based on the volume of residual caries/initial
      caries (RC/IC) and the mean mineral density (MD) at the cavity floor. MIP was
      determined by measuring the volume of the prepared cavity/initial cavity (PC/IC).
      RESULTS: Among the four groups, the LIF group had the smallest RC/IC (0.08), the
      highest mean MD at the cavity floor (1.32 g/cm(3) ) and the highest MIP (4.47).
      The CME group had the highest RC/IC (0.24), the lowest mean MD (1.01 g/cm(3) )
      and the lowest MIP (2.23). The CE group exhibited a more acceptable CRE (RC/IC =
      0.13, mean MD = 1.21 g/cm(3) ) but had a higher MIP (3.95). Both the CRE and MIP
      parameters of FACE technology were the second most acceptable (RC/IC = 0.12, mean
      MD = 1.13 g/cm(3) , MIP = 3.20) and did not differ significantly from the most
      acceptable. CONCLUSIONS: FACE is an effective caries removal technology for
      removing infected dentine without significantly increasing cavity size.

PMID- 24320904
TI  - A laboratory investigation of colour changes in two contemporary resin composites
      on exposure to spices.
AB  - BACKGROUND: The aim of this study was to evaluate colour stability upon exposure
      to spices of a nano-filled and a micro-hybrid resin composite finished either
      with Sof-LexTM discs (SLD) or against plastic strips (PS). METHODS: Forty
      cylindrical specimens of 3 mm thickness were fabricated from Filtek Supreme XT TM
      (FS) and Gradia Direct XTM (GD). The top surface of each specimen was polished
      with SLD while the bottom surface was finished against PS. All samples were
      immersed in staining solutions (0.1% weight turmeric, paprika and tamarind) and
      distilled water at 37  degrees C. Colour after 0, 24, 72 and 168 hours of
      immersion was recorded with a reflection spectrophotometer using CIE L*a*b*
      parameters and the results were statistically analysed with repeated measures of
      ANOVA and Bonferroni post hoc tests. RESULTS: Among all the staining solutions
      tested, the highest colour deviation was obtained in the turmeric group. FS
      finished against PS showed significantly more colour changes compared to
      specimens polished with SLD, while GD finished against PS were found to be more
      resistant to colour changes. CONCLUSIONS: Within the limitations of this study
      all the spices tested have the potential to stain resin composites with turmeric
      causing the most significant discolouration. Micro-hybrid and nano-filled resin
      composites appeared to respond differently to staining by spices when either
      finished with PS or polished with SLD.

PMID- 24320905
TI  - Role of arginine and fluoride in the prevention of eroded enamel: an in vitro
      model.
AB  - BACKGROUND: The aim of this study was to investigate the effect of arginine and
      fluoride on the reduction of erosive wear. METHODS: Bovine enamel blocks were
      randomly allocated into four groups (n = 20) and exposed to: ESPR group (8%
      arginine, 1450 ppm sodium monofluorophosphate, calcium carbonate and titanium
      dioxide); ESen group (1450 ppm sodium monofluorophosphate, 5% potassium citrate);
      positive control PC group (1500 ppm sodium monofluorophosphate) and negative
      control NC group (water). The samples were submitted to six alternating cycles of
      demineralization-remineralization (cola, 10 minutes; artificial saliva, 1 hour,
      respectively). Before and between cyclic demineralization and remineralization,
      blocks were treated with slurries of the respective toothpastes or water (1
      minute). Erosive tissue loss was analysed by microhardness and profilometry. Data
      were analysed by ANOVA and Tukey tests for individual comparisons among the
      groups (p < 0.05). RESULTS: In microhardness, the ESPR (217.46 +/- 55.45) group
      was significantly better than the other treatment groups (PC = 302.76 +/- 96.10;
      ESen = 315.56 +/- 74.56; p < 0.001). The ESPR group showed a similar loss to NC
      group (NC = 210.8 +/- 49.98; p = 0.991). The mean erosion depth (+/- SE, MUm) was
      detected between NC (14.37 +/- 1.72) and dentifrices tested (ESPR (4.11 +/-
      1.34), ESen group (7.64 +/- 1.61) and PC (8.20 +/- 2.19) (p = 0.000).
      CONCLUSIONS: From the results of the present study, the effectiveness of
      Sensitive Pro Relief in the prevention of erosive surface loss seems to be
      attributed to the possible effect of the arginine associated with fluoride.

PMID- 24320906
TI  - Clinical efficacy of a herbal dentifrice on dentinal hypersensitivity: a
      randomized controlled clinical trial.
AB  - BACKGROUND: Dentinal hypersensitivity is a common problem and there is a growing
      interest in herbal based formulations for the treatment of oral diseases. This
      study was conducted to assess the efficacy of a commercially available novel
      herbal dentifrice in reduction of dentinal hypersensitivity. METHODS: A total of
      73 subjects (38 males and 35 females; aged 25-60 years) were randomly divided
      into two groups: Group 1 - a placebo dentifrice (The Himalaya Drug Company
      Research and Development, Makali, Bangalore) and Group 2 - (test group), a
      commercially available herbal dentifrice (Hi Ora K, The Himalaya Drug Company
      Research and Development, Makali, Bangalore). Sensitivity scores for controlled
      air stimulus and cold water were recorded at baseline, 6 weeks and 12 weeks.
      RESULTS: The test group was found to be significantly better compared to the
      placebo group at the end of 6 and 12 weeks in reduction of dentinal
      hypersensitivity. CONCLUSIONS: The novel herbal dentifrice can be recommended for
      treatment of dentinal hypersensitivity.

PMID- 24320907
TI  - Effect of L-arginine dietary supplementation on salivary urea concentration and
      pH in physically active individuals.
AB  - BACKGROUND: The aim of this study was to assess if the consumption of 3 g of a
      commercially available L-arginine dietary supplement causes a postabsorptive rise
      in urea concentration or pH of unstimulated saliva in a group of physically
      active individuals. METHODS: Salivary urea and pH were determined for 117
      participants in a randomized double-blinded placebo-controlled study. Samples
      were collected by 'spitting' method in fasting conditions. One hour prior to
      their second visit, participants consumed three tablets of L-arginine or placebo.
      RESULTS: Urea concentration was significantly lower at second measurement for
      both the study and control group. The magnitude of the change was not significant
      between the groups. pH was higher for both groups at second measurement, but only
      significant for the study group. The magnitude of the change was significant
      between the groups. Participants who intermittently ingested protein dietary
      supplements and those with a Body Mass Index (BMI) higher than 25 had
      significantly higher basal urea concentration. CONCLUSIONS: The results of this
      study did not confirm the hypothesis. Further studies are needed to determine the
      effects of different doses of L-arginine supplements on the biochemical
      composition of saliva and the influence of their long-term consumption on the
      risk of developing dental diseases.

PMID- 24320908
TI  - Individual dental expenditure by Australian adults.
AB  - BACKGROUND: While dental service use in Australia has been extensively reported,
      little is known about associated costs. The aim of this article was to describe
      the annual individual dental expenditure of Australian adults. METHODS: Self
      reported service use and expenditure data were sourced from a sample of 3000
      adults aged 30 to 61 years who were randomly selected from the electoral roll.
      Bivariate associations between total individual dental expenditure and out-of
      pocket expenditure (fees less insurance rebate) and a range of participant
      characteristics were explored. RESULTS: Response rate for the baseline
      questionnaire was 39.4% and of these, 53.1% responded at 12-month follow-up. The
      mean total dental expenditure was $702 and mean out-of-pocket expenditure was
      $489. Toothache was associated with total dental expenditure; adults experiencing
      toothache had higher median expenditure ($445) than adults who hardly ever/never
      had toothache ($308) (p < 0.05). Dental insurance status was not associated with
      total expenditure, but insured had lower median out-of-pocket expenditure ($146)
      than uninsured adults ($320) (p < 0.01). CONCLUSIONS: Affordability variables
      typically associated with access to dental care, such as insurance status, were
      not associated with total expenditure, while poorer oral health was associated
      with higher total expenditures.

PMID- 24320909
TI  - Factors associated with colonization of Streptococcus mutans in 8- to 32-month
      old children: a cohort study.
AB  - BACKGROUND: The factors involved in Streptococcus mutans colonization in young
      children are not clear. The aim of this study was to determine the factors
      associated with S. mutans colonization in 8- to 32-month-old children. METHODS: A
      group of 225 caries-free 8-month-old children was recruited for the study. They
      were examined every six months until they were 32 months old to investigate their
      environmental factors, host factors and bacterial transmission factors. At
      baseline and during each examination, their teeth were checked for the presence
      of dental plaque and developmental defects of enamel, and S. mutans plaque status
      was assessed using a real-time PCR test. RESULTS: Eight children (3.6%) showed S.
      mutans colonization by the age of 8 months. The percentages of colonization were
      6.0% at 14 months, 16.2% at 20 months, 26.7% at 26 months, and 33.5% at 32
      months. The results showed that females (p = 0.006), children with enamel
      hypoplasia (p = 0.024), children with low birth weights (p = 0.005), those who
      consume more sweets (p < 0.001), and those with a higher proportion of visible
      plaque (p = 0.020 and p = 0.041) were more likely to be colonized by S. mutans.
      CONCLUSIONS: Streptococcus mutans colonization in young children was associated
      with gender, tooth enamel hypoplasia, low birth weight, frequent consumption of
      sweets and poor oral hygiene.

PMID- 24320910
TI  - Failure analysis of the ball bearings of dental air turbine handpieces.
AB  - BACKGROUND: The aim of this study was to identify the nature and causes of
      deterioration and failure in dental handpiece ball bearings and thus provide
      guidance for clinical handling for service longevity. METHODS: The bearings of 36
      turbine assemblies were dismantled for visual inspection, documented using a
      digital camera, and examined using scanning electron microscopy, as appropriate.
      RESULTS: For the metal parts of the ball bearing assembly, defects observed were
      mainly wear arising from the running load and corrosion. This was in the form of
      scratches and discoloured circumferential bands on the balls, and dull or worn
      surfaces extending around the circumference of the raceways. Cage damage
      including cracking, fracture, surface rubbing and distortion occurred, in varying
      degrees, in every failed turbine. CONCLUSIONS: Dental ball bearing failure modes
      have been identified. Cumulative effects of damage from corrosion and mechanical
      factors lead to handpiece deterioration. The cage was found to be very vulnerable
      to damage, and this may be the key limitation on bearing lifetime. Autoclaving
      may contribute to that, as it does to corrosion in the absence of adequate
      lubrication, but this seems to be minor in comparison to the effects of abuse.
      There is no justification for failing to observe usage and sterilization
      instructions.

PMID- 24320911
TI  - Superficial skin necrosis and neurological complications following administration
      of local anaesthetic: a case report.
AB  - Local anaesthesia is used routinely throughout dentistry. Complications are,
      however, relatively uncommon. A unique case of superficial skin necrosis and
      neurological symptoms following administration of local anaesthesia for dental
      treatment is reported and the possible mechanisms behind this unusual
      presentation are discussed. Awareness of this possible complication and its
      mechanism helps clinicians diagnose and manage patients with similar problems
      appropriately. 

PMID- 24320912
TI  - Oral health impact on quality of life among adults with disabilities: carer
      perceptions.

PMID- 24320916
TI  - Diabetes, wound healing and complications.

PMID- 24320917
TI  - Diabetes, wound healing and complications: authors' reply.

PMID- 24320918
TI  - Top 10 thoughts for dentistry in Australia.

PMID- 24320919
TI  - Developmental enamel defects in the primary dentition.

PMID- 24320920
TI  - Developmental enamel defects in the primary dentition: authors' reply.

PMID- 24320921
TI  - Jaw necrosis after herpes zoster infection due to HIV/AIDS as underlining
      disease.

PMID- 24320922
TI  - Efficacy of tooth mousse.

PMID- 24320923
TI  - Efficacy of tooth mousse: authors' reply.

PMID- 24320924
TI  - Tooth mousse in the prevention of ecc.

PMID- 24320925
TI  - Tooth mousse in the prevention of ecc: authors' reply.

PMID- 24320927
TI  - Change practice now! Using atraumatic needles to prevent post lumbar puncture
      headache.
AB  - BACKGROUND AND PURPOSE: Lumbar puncture (LP) is a key diagnostic procedure in
      medicine. Post lumbar puncture headache (PLPHA) is a well recognized complication
      of LP. Evidence suggests that using atraumatic needles for diagnostic LP (ATNLP)
      reduces risk of PLPHA. However, clinicians in Europe and the USA routinely use
      traumatic needles for diagnostic LP (TNLP). The occurrence of PLPHA following
      ATNLP and TNLP was compared in a clinical setting. Further, a survey was
      performed exploring use of ATNLP amongst UK neurologists. METHODS: Service
      development study. Patients were followed up 2 and 7 days after LP using blinded
      telephone assessment. A questionnaire was developed to assess use of ATNLP
      amongst UK neurologists. Frequency, onset, duration and severity of PLPHA were
      recorded as were use of analgesia, general practitioner consultations, hospital
      readmissions, days off work due to PLPHA and cost. Neurologists were asked about
      their familiarity with, and use of, ATNLP. RESULTS: One hundred and nine
      participants attending the Royal London Hospital were included, and 74 attendees
      of the Association of British Neurologists 2012 conference completed an on-site
      questionnaire. ATNLP reduced the rate of PLPHA (27.1% vs. 60.4%; P < 0.01). In
      those participants who developed PLPHA symptoms were short lived (mean 50 h vs.
      94 h, P = 0.02) and less severe after ATNLP. Use of ATNLP led to significant cost
      savings. Only one in five UK neurologists regularly use ATNLP stating lack of
      training and availability of atraumatic needles as main reasons. CONCLUSIONS:
      ATNLP significantly reduces the risk of PLPHA. Training is required 3 to
      facilitate a change from TNLP to ATNLP amongst clinicians.

PMID- 24320928
TI  - Acquired silky African hair, malnutrition, and chronic diseases.

PMID- 24320929
TI  - Environmental gradients predict the genetic population structure of a coral reef
      fish in the Red Sea.
AB  - The relatively recent fields of terrestrial landscape and marine seascape
      genetics seek to identify the influence of biophysical habitat features on the
      spatial genetic structure of populations or individuals. Over the last few years,
      there has been accumulating evidence for the effect of environmental
      heterogeneity on patterns of gene flow and connectivity in marine systems. Here,
      we investigate the population genetic patterns of an anemonefish, Amphiprion
      bicinctus, along the Saudi Arabian coast of the Red Sea. We collected nearly one
      thousand samples from 19 locations, spanning approximately 1500 km, and genotyped
      them at 38 microsatellite loci. Patterns of gene flow appeared to follow a
      stepping-stone model along the northern and central Red Sea, which was disrupted
      by a distinct genetic break at a latitude of approximately 19 degrees N. The Red
      Sea is characterized by pronounced environmental gradients along its axis,
      roughly separating the northern and central from the southern basin. Using mean
      chlorophyll-a concentrations as a proxy for this gradient, we ran tests of
      isolation by distance (IBD, R(2) = 0.52) and isolation by environment (IBE, R(2)
      = 0.64), as well as combined models using partial Mantel tests and multiple
      matrix regression with randomization (MMRR). We found that genetic structure
      across our sampling sites may be best explained by a combined model of IBD and
      IBE (Mantel: R(2) = 0.71, MMRR: R(2) = 0.86). Our results highlight the potential
      key role of environmental patchiness in shaping patterns of gene flow in species
      with pelagic larval dispersal. We support growing calls for the integration of
      biophysical habitat characteristics into future studies of population genetic
      structure. 

PMID- 24320930
TI  - Variable selection and prediction using a nested, matched case-control study:
      Application to hospital acquired pneumonia in stroke patients.
AB  - Matched case-control designs are commonly used in epidemiologic studies for
      increased efficiency. These designs have recently been introduced to the setting
      of modern imaging and genomic studies, which are characterized by high
      dimensional covariates. However, appropriate statistical analyses that adjust for
      the matching have not been widely adopted. A matched case-control study of 430
      acute ischemic stroke patients was conducted at Massachusetts General Hospital
      (MGH) in order to identify specific brain regions of acute infarction that are
      associated with hospital acquired pneumonia (HAP) in these patients. There are
      138 brain regions in which infarction was measured, which introduce nearly 10,000
      two-way interactions, and challenge the statistical analysis. We investigate
      penalized conditional and unconditional logistic regression approaches to this
      variable selection problem that properly differentiate between selection of main
      effects and of interactions, and that acknowledge the matching. This neuroimaging
      study was nested within a larger prospective study of HAP in 1915 stroke patients
      at MGH, which recorded clinical variables, but did not include neuroimaging. We
      demonstrate how the larger study, in conjunction with the nested, matched study,
      affords us the capability to derive a score for prediction of HAP in future
      stroke patients based on imaging and clinical features. We evaluate the proposed
      methods in simulation studies and we apply them to the MGH HAP study. 

PMID- 24320931
TI  - Type 2 segmental Hailey-Hailey disease with systematized bilateral arrangement.

PMID- 24320932
TI  - Characterization of the role of a highly conserved sequence in ATP binding
      cassette transporter G (ABCG) family in ABCG1 stability, oligomerization, and
      trafficking.
AB  - ATP-binding cassette transporter G1 (ABCG1) mediates cholesterol and oxysterol
      efflux onto lipidated lipoproteins and plays an important role in macrophage
      reverse cholesterol transport. Here, we identified a highly conserved sequence
      present in the five ABCG transporter family members. The conserved sequence is
      located between the nucleotide binding domain and the transmembrane domain and
      contains five amino acid residues from Asn at position 316 to Phe at position 320
      in ABCG1 (NPADF). We found that cells expressing mutant ABCG1, in which Asn316,
      Pro317, Asp319, and Phe320 in the conserved sequence were replaced with Ala
      simultaneously, showed impaired cholesterol efflux activity compared with wild
      type ABCG1-expressing cells. A more detailed mutagenesis study revealed that
      mutation of Asn316 or Phe 320 to Ala significantly reduced cellular cholesterol
      and 7-ketocholesterol efflux conferred by ABCG1, whereas replacement of Pro317 or
      Asp319 with Ala had no detectable effect. To confirm the important role of Asn316
      and Phe320, we mutated Asn316 to Asp (N316D) and Gln (N316Q), and Phe320 to Ile
      (F320I) and Tyr (F320Y). The mutant F320Y showed the same phenotype as wild type
      ABCG1. However, the efflux of cholesterol and 7-ketocholesterol was reduced in
      cells expressing ABCG1 mutant N316D, N316Q, or F320I compared with wild type
      ABCG1. Further, mutations N316Q and F320I impaired ABCG1 trafficking while having
      no marked effect on the stability and oligomerization of ABCG1. The mutant N316Q
      and F320I could not be transported to the cell surface efficiently. Instead, the
      mutant proteins were mainly localized intracellularly. Thus, these findings
      indicate that the two highly conserved amino acid residues, Asn and Phe, play an
      important role in ABCG1-dependent export of cellular cholesterol, mainly through
      the regulation of ABCG1 trafficking. 

PMID- 24320933
TI  - Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for
      the treatment of hepatitis C virus infection.
AB  - A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole
      difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was
      discovered. Optimization of antiviral potency and pharmacokinetics led to the
      identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31
      pM) has an extended plasma half-life of 37-45 h in healthy volunteers and
      produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg
      or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has
      been shown to be safe and efficacious, with SVR12 rates up to 100% when used in
      combination with direct-acting antivirals having complementary mechanisms.

PMID- 24320934
TI  - Five new compounds from Rhododendron mariae Hance.
AB  - Five new compounds (-)-(7R,8S,7'R,8'S)-4,9,4',9'-tetrahydroxy-3,3'-dimethoxy-7,7'
      epoxylignan 9-O-beta-d-xylopyranoside (1), (-)-(7'R,8'S)-5'-methoxyl(dimeric
      coniferyl acetate) (2), (+)-(1R,2S)-1,2-bis(4-hydroxy-3-methoxyphenyl)-3-acetyl
      1,3-propanediol (3), (-)-3-((2R,3R)-2-ethoxy-3-(hydroxymethyl)-7-methoxy-2,3
      dihydrobenzofuran-5-yl)propan-1-ol (4), and (+)-3-((2S,3S)-2-ethoxy-3
      (hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl)propan-1-ol (5), together
      with 12 known compounds, were isolated from an ethanol extract of the dried stems
      of Rhododendron mariae Hance. Their structures were elucidated by NMR, HR-MS, CD,
      ORD experiments and chemical methods. Compounds 2, 3, 6, and 17 exhibited
      significant inhibitory effects on the nitric oxide production in
      lipopolysaccharide activated C57BL6/J mouse macrophages. 

PMID- 24320936
TI  - Dynamics of an ultrafast folding subdomain in the context of a larger protein
      fold.
AB  - Small fast folding subdomains with low contact order have been postulated to
      facilitate the folding of larger proteins. We have tested this idea by
      determining how the fastest folding linear beta-hairpin, CLN025, which folds on
      the nanosecond time scale, folds within the context of a two-hairpin WW domain
      system, which folds on the microsecond time scale. The folding of the wild type
      FBP28 WW domain was compared to constructs in which each of the loops was
      replaced by CLN025. A combination of FTIR spectroscopy and laser-induced
      temperature-jump coupled with infrared spectroscopy was used to probe changes in
      the peptide backbone. The relaxation dynamics of the beta-sheets and beta-turn
      were measured independently by probing the corresponding bands assigned in the
      amide I region. The folding rate of the CLN025 beta-hairpin is unchanged within
      the larger protein. Insertion of the beta-hairpin into the second loop results in
      an overall stabilization of the WW domain and a relaxation lifetime five times
      faster than the parent WW domain. In both mutants, folding is initiated in the
      turns and the beta-sheets form last. These results demonstrate that fast folding
      subdomains can be used to speed the folding of more complex proteins, and that
      the folding dynamics of the subdomain is unchanged within the context of the
      larger protein. 

PMID- 24320935
TI  - Chondrocyte culture in three dimensional alginate sulfate hydrogels promotes
      proliferation while maintaining expression of chondrogenic markers.
AB  - The loss of expression of chondrogenic markers during monolayer expansion remains
      a stumbling block for cell-based treatment of cartilage lesions. Here, we
      introduce sulfated alginate hydrogels as a cartilage biomimetic biomaterial that
      induces cell proliferation while maintaining the chondrogenic phenotype of
      encapsulated chondrocytes. Hydroxyl groups of alginate were converted to sulfates
      by incubation with sulfur trioxide-pyridine complex (SO3/pyridine), yielding a
      sulfated material cross-linkable with calcium chloride. Passage 3 bovine
      chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up
      to 35 days. Cell proliferation was five-fold higher in alginate sulfate compared
      with alginate (p=0.038). Blocking beta1 integrins in chondrocytes within alginate
      sulfate hydrogels significantly inhibited proliferation (p=0.002). Sulfated
      alginate increased the RhoA activity of chondrocytes compared with unmodified
      alginate, an increase that was blocked by beta1 blocking antibodies (p=0.017).
      Expression and synthesis of type II collagen, type I collagen, and proteoglycan
      was not significantly affected by the encapsulation material evidenced by
      quantitative reverse transcription polymerase chain reaction (qRT-PCR) and
      immunohistochemistry. Alginate sulfate constructs showed an opaque appearance in
      culture, whereas the unmodified alginate samples remained translucent. In
      conclusion, alginate sulfate provides a three dimensional microenvironment that
      promotes both chondrocyte proliferation and maintenance of the chondrogenic
      phenotype and represents an important advance for chondrocyte-based cartilage
      repair therapies providing a material in which cell expansion can be done in
      situ. 

PMID- 24320937
TI  - Trends in mortality rates from coronary heart disease in Belgrade (Serbia) during
      the period 1990-2010: a joinpoint regression analysis.
AB  - BACKGROUND: Coronary heart disease (CHD) causes an estimated 7 million deaths
      worldwide each year. In the last few decades, mortality from CHD has been
      decreasing in many countries. The aim of this study was to analyze the trends of
      mortality from CHD and myocardial infarction (MI) in the population of Belgrade
      during the period 1990-2010. METHODS: Mortality data for CHD and MI were obtained
      from the Municipal Institute of Statistics in Belgrade and used to calculate age-
      and sex-specific and age-adjusted mortality rates. Joinpoint regression analysis
      was used to estimate annual percent changes (APCs) in mortality and to identify
      points in time where significant changes in trend occur. RESULTS: Trends in CHD
      mortality rates showed significant decline in men during the period studied (APC 
      0.5%, no joinpoints detected), but no significant change among women (APC +0.4%,
      no joinpoints detected). While we observed significant declines in CHD mortality
      in men aged 35-44, 55-64 and 65-74 and women aged 55-64, there was a significant
      increase in mortality in men aged >=85 and women aged 75-84 and >=85. Trends in
      MI mortality rates showed similar patterns in both genders, with a significant
      decline from the mid-1990s. Significant decline in MI mortality was observed in
      almost all age groups, except the two oldest (75-84 and >=85) in women
      population. CONCLUSIONS: Given that CHD and MI mortality trends showed different
      patterns during the period studied, especially in women, our results imply that
      further observation of trend is needed.

PMID- 24320938
TI  - Hexanoic acid protects tomato plants against Botrytis cinerea by priming defence
      responses and reducing oxidative stress.
AB  - Treatment with the resistance priming inducer hexanoic acid (Hx) protects tomato
      plants from Botrytis cinerea by activating defence responses. To investigate the
      molecular mechanisms underlying hexanoic acid-induced resistance (Hx-IR), we
      compared the expression profiles of three different conditions: Botrytis-infected
      plants (Inf), Hx-treated plants (Hx) and Hx-treated + infected plants (Hx+Inf).
      The microarray analysis at 24 h post-inoculation showed that Hx and Hx+Inf plants
      exhibited the differential expression and priming of many Botrytis-induced genes.
      Interestingly, we found that the activation by Hx of other genes was not altered
      by the fungus at this time point. These genes may be considered to be specific
      targets of the Hx priming effect and may help to elucidate its mechanisms of
      action. It is noteworthy that, in Hx and Hx+Inf plants, there was up-regulation
      of proteinase inhibitor genes, DNA-binding factors, enzymes involved in plant
      hormone signalling and synthesis, and, remarkably, the genes involved in
      oxidative stress. Given the relevance of the oxidative burst occurring in plant
      pathogen interactions, the effect of Hx on this process was studied in depth. We
      showed by specific staining that reactive oxygen species (ROS) accumulation in
      Hx+Inf plants was reduced and more restricted around infection sites. In
      addition, these plants showed higher ratios of reduced to oxidized glutathione
      and ascorbate, and normal levels of antioxidant activities. The results obtained
      indicate that Hx protects tomato plants from B. cinerea by regulating and priming
      Botrytis-specific and non-specific genes, preventing the harmful effects of
      oxidative stress produced by infection. 

PMID- 24320939
TI  - Going the distance: Memory and control processes in active dependency
      construction.
AB  - Filler-gap dependencies make strong demands on working memory in language
      comprehension because they cannot always be immediately resolved. In a series of
      three reading-time studies, we test the idea that these demands can be decomposed
      into active maintenance processes and retrieval events. Results indicate that the
      fact that a displaced phrase exists and the identity of its basic syntactic
      category both immediately impact comprehension at potential gap sites. In
      contrast, specific lexical details of the displaced phrase show an immediate
      effect only for short dependencies and a much later effect for longer
      dependencies. We argue that coarse-grained information about the filler is
      actively maintained and is used to make phrase structure parsing decisions,
      whereas finer grained information is more quickly released from active
      maintenance and consequently has to be retrieved at the gap site.

PMID- 24320940
TI  - Nano Ag-deposited BaTiO3 hybrid particles as fillers for polymeric dielectric
      composites: toward high dielectric constant and suppressed loss.
AB  - Nano Ag-deposited BaTiO3 (BT-Ag) hybrid particles usable as fillers for flexible
      polymeric composites to obtain high dielectric constant, low conductivity, and
      low dielectric loss were developed. BT-Ag hybrid particles were synthesized via a
      seed-mediated growing process by a redox reaction between silver nitrate and
      ethylene glycol. Nano Ag particles with a size less than 20 nm were discretely
      grown on the surface of the 100 nm BaTiO3. The similar lattice spacing of the (1
      1 1) planes of BT and Ag led to the hetero-epitaxial growth of Ag on the BT
      surface. The thickness of the coherent interface was about 3 nm. The adhesion of
      Ag to BT efficiently prevented the continuous contact between Ag particles in the
      polyvinylidene fluoride (PVDF) matrix and suppressed the formation of the
      conducting path in the composite. As a result, with a filler loading of 43.4 vol
      %, the composite exhibited a dielectric constant (Dk) value of 94.3 and
      dielectric loss (tan delta) of 0.06 at 1 kHz. An even higher Dk value of 160 at 1
      kHz (16 times larger than that of PVDF) was obtained when the content of BT-Ag
      was further increased, with low conductivity (sigma < 10(-5) S m(-1)) and low
      dielectric loss (tan delta = 0.11), demonstrating promising applications in the
      electronic devices. 

PMID- 24320941
TI  - Low concordance of biomarkers in histopathological and cytological material from
      breast cancer.
AB  - AIMS: The aim of this study was to investigate in primary breast cancer the
      congruency of routine clinical predictive biomarker evaluations, including ER, PR
      and Ki67, obtained using immunocytochemistry (ICC) and immunohistochemistry
      (IHC). METHODS AND RESULTS: Clinicopathological data were collected on all women
      diagnosed with primary breast cancer at Karolinska University Hospital in 2011. A
      total of 346 patients were included in a retrospective paired comparison of
      predictive biomarker evaluations on direct smear ICC and IHC. This showed a low
      congruency between findings with the two methods, especially evident for Ki67
      (kappa = 0.35-0.42). By suggested adjustments to ICC cut-offs, we managed to
      improve the inter-rater agreement of Ki67 classification slightly to kappa =
      0.46. CONCLUSIONS: Our findings suggest that routine clinical ICC and IHC
      evaluations of predictive biomarkers produce discordant results. Consequently,
      basing therapeutic decisions on cytology with cut-offs defined for IHC induces a
      risk that patients will receive suboptimal therapy. However, our analysis shows
      that local adjustments to biomarker cut-off levels may improve congruency and
      increase the probability of correct classifications.

PMID- 24320942
TI  - Traumatic brain injury and PTSD screening efforts evaluated using latent class
      analysis.
AB  - OBJECTIVE: To empirically identify latent classes of service members according to
      persistent postconcussive symptom patterns and to characterize the identified
      classes relative to other postdeployment variables including posttraumatic stress
      disorder (PTSD) and mild traumatic brain injury (TBI) screening results. Such
      comparisons may directly inform policy regarding these routine assessments and
      translate to improved treatment decisions. METHOD: Self-report data were obtained
      for 12,581 combat-exposed male U.S. Navy and Marine Corps personnel who returned
      from deployment in 2008-2009 and completed a Post-Deployment Health Assessment
      (PDHA) and an associated Post-Deployment Health Reassessment (PDHRA). Persistent
      postconcussive symptoms indicated on the PDHRA were used as manifest variables in
      a latent class analysis yielding 4 distinct classes: systemic,
      cognitive/behavioral, comorbid, and nonpresenting. RESULTS: Although the
      nonpresenting class endorsed few or no postconcussive symptoms, the systemic and
      cognitive/behavioral classes displayed elevated likelihoods of neurological and
      mental health symptoms, respectively. Members of the comorbid class had an
      increased probability of reporting a wide range of symptoms across both domains.
      Characterization of identified classes suggested that class membership may
      indicate the presence or absence of persistent conditions resulting from head
      injury and/or mental health issues. Under this assumption, estimated class
      membership probabilities implied a rate of probable neurological injury among
      this sample to be 17.9%, whereas the standard assessments aimed at identifying
      repercussions of mild TBI reported a positive screening rate of only 13.1%.
      CONCLUSIONS: Findings suggest that the routinely administered PDHA and PDHRA
      appear to underestimate the true prevalence of service members experiencing
      postdeployment health problems. Supplemental items or an alternative screening
      algorithm incorporating persistent postconcussive symptoms may enable
      identification of additional cases requiring treatment following return from
      deployment.

PMID- 24320943
TI  - The personal importance of being independent: associations with changes in
      disability and depressive symptoms.
AB  - OBJECTIVE: This study examined the role of independence centrality (the personal
      importance of being functionally independent) in adapting to functional
      disability in persons with spinal cord injury (SCI). We assessed how changes in
      disability related to changes in depressive symptoms, the association between
      independence centrality and depressive symptoms, and the role of independence
      centrality in moderating the association between changes in disability and
      changes in depressive symptoms. METHOD: Using data from a randomized controlled
      trial, we focused on 173 survivors of SCI who completed baseline and 12-month
      follow-up measures of independence centrality, disability (activities of daily
      living and instrumental activities of daily living needs), and depressive
      symptoms. RESULTS: Consistent with our predictions, increased disability was
      related to increased depressive symptoms, and higher independence centrality was
      associated with more depressive symptoms at baseline. Consistent with the life
      span theory of control, SCI survivors with high independence centrality
      experienced more depressive symptoms when disability increased, but less
      depressive symptoms when disability decreased. Survivors of SCI with low
      independence centrality were less affected by changing levels of disability.
      CONCLUSION: Persons with SCI with high independence centrality have higher levels
      of depressive symptoms and are more responsive to changes in functional status.
      Given the functional status trajectories of survivors of SCI, having low
      independence centrality may be adaptive because it facilitates disengagement from
      unattainable goals.

PMID- 24320944
TI  - Social support as a moderator of functional disability's effect on depressive
      feelings in early rheumatoid arthritis: a four-year prospective study.
AB  - OBJECTIVE: To examine associations of depressive feelings with disease-related
      variables and explore the moderating effect of social support on depressive
      feelings in individuals with early rheumatoid arthritis (RA) prospectively over 4
      years. METHOD: Data were collected annually over 4 years. The sample consisted of
      124 individuals with diagnosed RA (85.5% women; mean age 47.9 years; mean disease
      duration 22.2 months). The strength of cross-sectional and prospective
      associations of sociodemographic, disease-related variables and the direct and
      moderating effects of social support on depression were tested using
      correlations, multilevel models, and hierarchical linear regressions. RESULTS:
      The study showed that emotional support moderated the influence of functional
      disability on depressive feelings in individuals with RA. This was not detected
      for instrumental support. Further prospective associations between functional
      status, marital status, and depressive feelings were also found. Overall, the
      strongest association was found between initial depressive feelings and
      depressive feelings over time. CONCLUSIONS: Initial depression seemed to be a
      risk factor in explaining later depressive feelings, but emotional support might
      be prospectively beneficial, especially for individuals with higher levels of
      disability. Early detection of individuals at risk for depression and providing
      interventions aimed at the specific functions of social support might help to
      decrease mental health problems.

PMID- 24320945
TI  - Exploring the longitudinal stability of the CSQ24 in a back pain population.
AB  - OBJECTIVE: The CSQ24 is a shortened version of the Coping Strategies
      Questionnaire and includes 24 items and four factors-Catastrophizing, Diversion,
      Reinterpreting, and Cognitive Coping. The factor structure of the CSQ has been a
      matter for debate for some time. This study aimed to explore the stability of the
      factor structure of the CSQ24 using repeated measurements in a back pain
      population at assessment, after physiotherapy treatment, and at 6 and 12 months
      after treatment. METHOD: A consecutive sample of 194 adults with chronic low back
      pain was recruited over 24 months. They completed the CSQ24, with other measures
      of pain, disability and mood, on 4 occasions. Ninety-six participants
      satisfactorily completed and returned both 6- and 12-month longitudinal follow-up
      questionnaires. RESULTS: Exploratory Factor Analysis showed, at each time point,
      a 4-factor structure of Catastrophizing, Cognitive Coping, Diversion, and
      Reinterpreting. Within each factor, the factor scores at each time point were
      significantly correlated and showed good internal reliability. This stability was
      demonstrated against a background of significant change in measures of pain,
      disability, and mood. CONCLUSIONS: These results provide support for the 4-factor
      structure of the CSQ24 and its longitudinal stability. Argument is provided for
      the need to explore the longitudinal stability of related tools in populations
      that undergo change as a result of treatment.

PMID- 24320946
TI  - Self-efficacy as a predictor of self-reported physical, cognitive, and social
      functioning in multiple sclerosis.
AB  - OBJECTIVE: The objective of this study was to investigate whether self-efficacy
      is associated with physical, cognitive, and social functioning in individuals
      with multiple sclerosis (MS) when controlling for disease-related characteristics
      and depressive symptomatology. METHOD: Study subjects were 81 individuals between
      the ages of 29 and 67 with a diagnosis of clinically definite MS. Hierarchical
      regression analysis was used to examine the relationships between self-efficacy
      and self-reported physical, cognitive, and social functioning. RESULTS: Self
      efficacy is a significant predictor of self-reported physical, cognitive, and
      social functioning in MS after controlling for variance due to disease-related
      factors and depressive symptomatology. CONCLUSIONS: Self-efficacy plays a
      significant role in individual adjustment to MS across multiple areas of
      functional outcome beyond that which is accounted for by disease-related
      variables and symptoms of depression.

PMID- 24320948
TI  - Pigmentation in Xiphophorus: an emerging system in ecological and evolutionary
      genetics.
AB  - The genus Xiphophorus has great potential to contribute to the study of
      vertebrate pigmentation and elucidating the relative influence of ecology,
      physiology, and behavior on evolution at the molecular level. More importantly,
      the association between pigmentation and a functional oncogene offers the
      potential to understand the evolution and maintenance of cancer-causing genetic
      elements. Using criteria laid out recently in the literature, I demonstrate the
      power of the Xiphophorus system for studying pigment evolution through
      integrative organismal biology. Using the most recent phylogeny, the phylogenetic
      distribution of several important pigmentation loci are reevaluated. I then
      review support for existing hypotheses of the functional importance of
      pigmentation. Finally, new observations and hypotheses regarding some of the
      characteristics of pigment patterns in natural populations and open questions and
      future directions in the study of the evolution of these traits are discussed.

PMID- 24320947
TI  - Thrombolytic therapy with intravenous recombinant tissue plasminogen activator in
      Japanese older patients with acute ischemic stroke: Fukuoka Stroke Registry.
AB  - AIM: The present study aimed to determine the efficacy and safety of thrombolytic
      therapy with recombinant tissue plasminogen activator (rt-PA) therapy in older
      patients compared with younger patients. METHODS: Using the Fukuoka Stroke
      Registry, a prospective multicenter study for acute stroke in Japan, we analyzed
      data of 401 patients with acute ischemic stroke (aged 74.5 +/- 13.1 years)
      treated with thrombolytic therapy using rt-PA. Patients were categorized into two
      groups according to age: those aged >= 75 years (n=240) and <75 years (n=161).
      Neurological improvement was defined as a decrease in the National Institute of
      Health Stroke Scale (NIHSS) score of >= 4 during hospitalization or an NIHSS
      score of 0 at discharge. Good functional outcome was defined as a modified Rankin
      scale score of 0-2 at 3 months after onset. RESULTS: Neurological symptoms at
      admission were more severe in older patients than in younger patients. Old age
      (>= 75 years) was not associated with neurological deterioration (multivariate
      adjusted odds ratio [OR] 0.90, 95% confidence interval [CI] 0.46-1.77),
      neurological improvement (multivariate-adjusted OR 0.91, 95% CI 0.54-1.53) and
      symptomatic intracranial hemorrhage (multivariate-adjusted OR 1.11, 95% CI 0.19
      8.87). Old age was negatively associated with good functional outcome
      (multivariate-adjusted OR 0.29, 95% CI 0.16-0.52) and positively associated with
      in-hospital mortality (multivariate-adjusted OR 19.3, 95% CI 2.4-474.9).
      CONCLUSIONS: In patients treated with rt-PA, old age is associated with poor
      functional outcome and in-hospital mortality. However, the probability of
      neurological improvement and symptomatic intracranial hemorrhage in older
      patients is comparable with that in younger patients.

PMID- 24320949
TI  - Total synthesis of the marine alkaloid Mansouramycin D.
AB  - Mansouramycin D, a cytotoxic alkaloid was isolated from a marine Streptomyces sp.
      in 2009. The first, simple, and concise route to the total synthesis of
      Mansouramycin D is reported. The core structure of the isoquinoline ring has been
      constructed from iminoannulation of 2-alkynylbenzaldehyde followed by
      oxidation/deprotection and oxidative amination via a three-step sequence from
      easily accessible starting materials. 

PMID- 24320950
TI  - Oxidative damage in MauG: implications for the control of high-valent iron
      species and radical propagation pathways.
AB  - The di-heme enzyme MauG catalyzes the oxidative biosynthesis of a tryptophan
      tryptophylquinone cofactor on a precursor of the enzyme methylamine dehydrogenase
      (preMADH). Reaction of H2O2 with the diferric form of MauG, or reaction of O2
      with diferrous MauG, forms the catalytic intermediate known as bis-Fe(IV), which
      acts as the key oxidant during turnover. The site of substrate oxidation is more
      than 40 A from the high-spin heme iron where H2O2 initially reacts, and catalysis
      relies on radical hopping through an interfacial residue, Trp199 of MauG. In the
      absence of preMADH, the bis-Fe(IV) intermediate is remarkably stable, but
      repeated exposure to H2O2 results in suicide inactivation. Using mass
      spectrometry, we show that this process involves the oxidation of three Met
      residues (108, 114, and 116) near the high-spin heme through ancillary electron
      transfer pathways engaged in the absence of substrate. The mutation of a
      conserved Pro107 in the distal pocket of the high-spin heme results in a dramatic
      increase in the level of oxidation of these Met residues. These results
      illustrate structural mechanisms by which MauG controls reaction with its high
      valent heme cofactor and limits uncontrolled oxidation of protein residues and
      loss of catalytic activity. The conservation of Met residues near the high-spin
      heme among MauG homologues from different organisms suggests that eventual
      deactivation of MauG may function in a biological context. That is, methionine
      oxidation may represent a protective mechanism that prevents the generation of
      reactive oxygen species by MauG in the absence of preMADH. 

PMID- 24320951
TI  - A Bayesian extension of the hypergeometric test for functional enrichment
      analysis.
AB  - Functional enrichment analysis is conducted on high-throughput data to provide
      functional interpretation for a list of genes or proteins that share a common
      property, such as being differentially expressed (DE). The hypergeometric P-value
      has been widely used to investigate whether genes from pre-defined functional
      terms, for example, Gene Ontology (GO), are enriched in the DE genes. The
      hypergeometric P-value has three limitations: (1) computed independently for each
      term, thus neglecting biological dependence; (2) subject to a size constraint
      that leads to the tendency of selecting less-specific terms; (3) repeated use of
      information due to overlapping annotations by the true-path rule. We propose a
      Bayesian approach based on the non-central hypergeometric model. The GO
      dependence structure is incorporated through a prior on non-centrality
      parameters. The likelihood function does not include overlapping information. The
      inference about enrichment is based on posterior probabilities that do not have a
      size constraint. This method can detect moderate but consistent enrichment
      signals and identify sets of closely related and biologically meaningful
      functional terms rather than isolated terms. We also describe the basic ideas of
      assumption and implementation of different methods to provide some theoretical
      insights, which are demonstrated via a simulation study. A real application is
      presented. 

PMID- 24320952
TI  - Effects of the local alcohol environment on adolescents' drinking behaviors and
      beliefs.
AB  - AIMS: To examine relationships between characteristics of the local alcohol
      environment and adolescent alcohol use and beliefs in 50 California cities.
      DESIGN: The study used longitudinal survey data collected from adolescents; city
      level measures of local alcohol policy comprehensiveness, policy enforcement,
      adult drinking and bar density; and multi-level modeling with three levels (city,
      individual, time), allowing for random effects. Models included interaction terms
      (time * alcohol environment characteristics) and main effects, controlling for
      city and youth demographic characteristics. Analyses also examined possible
      mediating effects of alcohol-related beliefs. SETTING: Fifty California cities
      (50000-500000 population). PARTICIPANTS: Random samples of 1478 adolescents and
      8553 adults. MEASUREMENTS: Past-year alcohol use and heavy drinking, and alcohol
      related beliefs (e.g. perceived alcohol availability) among adolescents; past 28
      day alcohol use among adults; ratings of local alcohol control policies; funding
      for enforcement activities; bars per roadway mile. FINDINGS: Local alcohol policy
      comprehensiveness and enforcement were associated with lower levels of past-year
      alcohol use (betas=-0.003 and -0.085, P<0.05). Bar density was associated with a
      higher level of past-year alcohol use (beta=1.086, P<0.01). A greater increase in
      past-year alcohol use and heavy drinking over time was observed among adolescents
      living in cities with higher levels of adult drinking (betas=0.224 and 0.108,
      P<0.01). Effects of bar density appeared to be mediated through perceived alcohol
      availability and perceived approval of alcohol use. CONCLUSIONS: Adolescent
      alcohol use and heavy drinking are related to characteristics of the local
      alcohol environment, including alcohol control policies, enforcement, adult
      drinking and bar density. Change in adolescents' drinking appears to be
      influenced by community-level adult drinking. Bar density effects appear to be
      mediated through perceived alcohol availability and approval of alcohol use.

PMID- 24320953
TI  - Modifiable risk factors in periodontitis: at the intersection of aging and
      disease.
AB  - Chronic inflammation is a prominent feature of aging and of common age-related
      diseases, including atherosclerosis, cancer and periodontitis. This volume
      examines modifiable risk factors for periodontitis and other chronic inflammatory
      diseases. Oral bacterial communities and viral infections, particularly with
      cytomegalovirus and other herpesviruses, elicit distinct immune responses and are
      central in the initiation of periodontal diseases. Risk of disease is dynamic and
      changes in response to complex interactions of genetic, environmental and
      stochastic factors over the lifespan. Many modifiable risk factors, such as
      smoking and excess caloric intake, contribute to increases in systemic markers of
      inflammation and can modify gene regulation through a variety of biologic
      mechanisms (e.g. epigenetic modifications). Periodontitis and other common
      chronic inflammatory diseases share multiple modifiable risk factors, such as
      tobacco smoking, psychological stress and depression, alcohol consumption,
      obesity, diabetes, metabolic syndrome and osteoporosis. Interventions that target
      modifiable risk factors have the potential to improve risk profiles for
      periodontitis as well as for other common chronic diseases.

PMID- 24320954
TI  - Composition and development of oral bacterial communities.
AB  - The oral bacterial microbiome encompasses approximately 700 commonly occurring
      phylotypes, approximately half of which can be present at any time in any
      individual. These bacteria are largely indigenous to the oral cavity; this
      limited habitat range suggests that interactions between the various phylotypes,
      and between the phylotypes and their environment, are crucial for their
      existence. Molecular cataloging has confirmed many basic observations on the
      composition of the oral microbiome that were formulated well before ribosomal RNA
      based systematics, but the power and the scope of molecular taxonomy have
      resulted in the discovery of new phylotypes and, more importantly, have made
      possible a level of bacterial community analysis that was unachievable with
      classical methods. Bacterial community structure varies with location within the
      mouth, and changes in community structure are related to disease initiation and
      disease progression. Factors that influence the formation and the evolution of
      communities include selective adherence to epithelial or tooth surfaces, specific
      cell-to-cell binding as a driver of early community composition, and
      interorganismal interaction leading to alteration of the local environment, which
      represents the first step on the road to oral disease. A comprehensive
      understanding of how these factors interact to drive changes in the composition
      of the oral microbial community can lead to new strategies for the inhibition of
      periodontal diseases and dental caries.

PMID- 24320955
TI  - Biology and pathogenesis of cytomegalovirus in periodontal disease.
AB  - Human periodontitis is associated with a wide range of bacteria and viruses and
      with complex innate and adaptive immune responses. Porphyromonas gingivalis,
      Tannerella forsythia, Aggregatibacter actinomycetemcomitans, Treponema denticola,
      cytomegalovirus and other herpesviruses are major suspected pathogens of
      periodontitis, and a combined herpesvirus-bacterial periodontal infection can
      potentially explain major clinical features of the disease. Cytomegalovirus
      infects periodontal macrophages and T-cells and elicits a release of interleukin
      1beta and tumor necrosis factor-alpha. These proinflammatory cytokines play an
      important role in the host defense against the virus, but they also have the
      potential to induce alveolar bone resorption and loss of periodontal ligament.
      Gingival fibroblasts infected with cytomegalovirus also exhibit diminished
      collagen production and release of an increased level of matrix
      metalloproteinases. This article reviews innate and adaptive immunity to
      cytomegalovirus and suggests that immune responses towards cytomegalovirus can
      play roles in controlling, as well as in exacerbating, destructive periodontal
      disease.

PMID- 24320957
TI  - Influence of sex steroids on inflammation and bone metabolism.
AB  - Sex steroids are central to sexual development and reproduction, exerting
      pleiotropic effects on multiple tissues and organs throughout the lifespan of
      humans. Sex steroids are fundamental to skeletal development, bone homeostasis
      and immune function. The composite effect of sex-specific genetic architecture
      and circulating levels of sex-steroid hormones closely parallels differences in
      the immune response and may account for corresponding sex-related differences in
      risk for chronic periodontitis, with men exhibiting greater susceptibility than
      women. Age-associated reductions in sex steroids also provide insight into
      apparent temporal increases in susceptibility to periodontitis and alveolar bone
      loss, particularly among women. Chronic infection and inflammatory conditions,
      such as periodontal disease, provide a unique platform for exploring the
      interface of sex steroids, immunity and bone metabolism.

PMID- 24320958
TI  - Modifiable risk factors in periodontal disease: epigenetic regulation of gene
      expression in the inflammatory response.
AB  - Epigenetics as a modifiable risk factor in periodontal diseases has been
      investigated in light of the current knowledge of how chronic infection and
      inflammation can affect gene-specific epigenetic reprogramming in periodontal
      tissues. Epigenomic programming might be particularly sensitive to environmental
      influences, and a combination of physiological stressors and environmental
      exposures appears to affect the epigenomic program acquired by a cell during
      differentiation and throughout the cellular lineage lifespan. Viral and bacterial
      infections can establish several types of epigenetic modifications, which
      sometimes engage in a complex epigenetic crosstalk also reflecting in the
      establishment and progress of periodontal diseases. The inflammatory and
      metabolic states of the periodontal tissues are driven by the infectious stimuli,
      and the magnitude of the cellular and molecular signature response is further
      dictated by the host genetic and epigenetic traits associated with various
      systemic exposures, including smoking, obesity and diabetes/hyperglycemia. This
      review discusses the advances in epigenetics, focusing on the role of DNA
      methylation in the pathogenesis of periodontal disease and the potential of
      epigenetic therapy.

PMID- 24320959
TI  - Smoking and inflammation: evidence for a synergistic role in chronic disease.
AB  - Tobacco smoking is the most important preventable risk factor for periodontitis;
      however, the underlying biological mechanisms responsible for the detrimental
      effects of smoking on periodontal health remain largely unclear. It is also well
      established that smoking has a negative impact on several inflammatory diseases,
      including rheumatoid arthritis, multiple sclerosis and inflammatory bowel
      disease. The aim of this paper was to review smoking-related changes in local and
      systemic host responses with a focus on cellular and molecular effects that could
      explain a hyperinflammatory response leading to periodontal destruction.
      Biological mechanisms that may be common to periodontal disease and other chronic
      inflammatory diseases were also explored, together with gene-smoking
      interactions. An epidemiologic perspective on the burden of smoking on
      periodontal health and the potential for smoking cessation is also presented.
      Tobacco smoking seems to induce changes ranging from decreased leukocyte
      chemotaxis to decreased production of immunoglobulins. Smoking also seems to
      cause a stronger inflammatory reaction with an increased release of potentially
      tissue-destructive substances (e.g. reactive oxygen species, collagenase, serine
      proteases and proinflammatory cytokines). These findings support a hypothesis
      that periodontitis is a hyperinflammatory condition rather than a hypo
      inflammatory condition.

PMID- 24320960
TI  - Role of chronic stress and depression in periodontal diseases.
AB  - An extensive body of experimental and clinical evidence documents the negative
      impact of chronic psychological stress and depression on the immune system and
      health. Chronic stress and depression can result in general dysregulation of the
      immune system, of both cellular and humoral pathways, which may contribute to
      pathogenic infection and concomitant periodontal tissue destruction. In general,
      the evidence is consistent with the hypothesis that stress can modify the host
      defense and progression of periodontal infections in patients susceptible to
      periodontitis. However, substantial evidence also indicates that these conditions
      can mediate risk for disease, including periodontitis, through changes in health
      related behaviors, such as oral hygiene, smoking and diet. The unequivocal
      interpretation of studies has also been hampered, in part, by issues related to
      conceptualization of stress and depression, as well as commonly associated
      comorbidities, such as diabetes, that can modify the onset and progression of
      periodontal disease. In addition, stress and depression appear to fall into a
      spectrum, ranging from mild to severe, involving a complex interaction of genetic
      background, coping strategies and environment. Differences in the
      conceptualization of stress and depression are probably important in assessing
      associations with other biologic and clinical measures. Future studies are
      necessary to clarify the complex interactions of chronic stress and depression in
      periodontal diseases. 

PMID- 24320961
TI  - Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared
      pathology via oxidative stress and mitochondrial dysfunction?
AB  - As many diseases have been shown to have several or indirect causes (i.e. are
      multifactorial) the question is what is the relative importance of each factor in
      a given disease? Also, what happens when some diseases, although apparently
      disparate, share causative factors and/or tissue pathologies? Host inflammation
      response mechanisms are largely shared by the body's different tissues and
      systems and only recently has special attention been paid to the possible
      linkages among chronic periodontitis and other chronic systemic diseases. The aim
      of this review was to consider and discuss the mounting evidence that the basis
      for the inter-relationships between chronic periodontitis and atheromatous
      disease and diabetes lie at a fundamental intracellular level, namely oxidative
      stress and mitochondrial dysfunction, as a meeting background among such chronic
      diseases and periodontitis.

PMID- 24320956
TI  - Inflammatory and immune pathways in the pathogenesis of periodontal disease.
AB  - The pathogenesis of periodontitis involves a complex immune/inflammatory cascade
      that is initiated by the bacteria of the oral biofilm that forms naturally on the
      teeth. The susceptibility to periodontitis appears to be determined by the host
      response; specifically, the magnitude of the inflammatory response and the
      differential activation of immune pathways. The purpose of this review was to
      delineate our current knowledge of the host response in periodontitis. The role
      of innate immunity, the failure of acute inflammation to resolve (thus becoming
      chronic), the cytokine pathways that regulate the activation of acquired immunity
      and the cells and products of the immune system are considered. New information
      relating to regulation of both inflammation and the immune response will be
      reviewed in the context of susceptibility to, and perhaps control of,
      periodontitis.

PMID- 24320962
TI  - Nutrigenomics: the role of nutrients in gene expression.
AB  - Improved understanding of the mechanism behind periodontal tissue destruction,
      the potential protective role of nutrients and the advent of modern genomic
      measurement tools has led to an increased interest in the association between
      nutrition and periodontal disease. To date, evidence for a direct link between
      periodontal disease and nutrition has come mainly from large observational cross
      sectional studies or very small double-blind randomized supplementation trials,
      with a large proportion finding no significant association between the nutrient
      being analyzed and markers of periodontal disease status. The advent of the
      'genomic era' has introduced the concept of nutrigenomic studies, which aim to
      reveal the relationship between nutrition and the genome to provide a scientific
      basis for improved public health through dietary means. Used alongside relatively
      inexpensive high-throughput technology, this will allow the effect of diet on the
      etiology of periodontal disease to be studied in greater detail. As it is
      extremely likely that interactions between genotype and diet are important in
      determining the risk of the most common complex diseases, it is highly probable
      that these interactions will be important in determining periodontal disease
      risk. Numerous nutritional genetic studies where the outcome measures have been
      markers of disease risk, most notably cardiovascular disease and cancer, provide
      proof of principle, highlight the importance of understanding these interactions
      and illustrate where the effect of dietary modification on periodontal disease
      progression may have been overlooked previously by observational studies.

PMID- 24320963
TI  - Dietary modulation of the inflammatory cascade.
AB  - Dietary supplementation has traditionally consisted of adding vitamins and/or
      minerals to correct or prevent a nutritional deficiency. When supplementing the
      diet with other inflammatory mediators, such as essential fatty acids, there is
      an adjunctive benefit to the standard therapies used in the control of chronic
      inflammatory diseases such as Crohn's disease or rheumatoid arthritis. This
      review focuses on the strategies utilized for therapeutic modulation of the
      inflammatory cascade through dietary supplementation with specific biomolecules.
      Examples of how these biomolecules affect local and systemic immune responses to
      chronic inflammation are examined. In particular, an overview of the literature
      identifying the potential to modify the host response to chronic periodontitis is
      provided.

PMID- 24320964
TI  - Systemic medication and the inflammatory cascade.
AB  - Periodontal disease is caused by inflammatory processes initiated by the presence
      of a biofilm. The management of this disease process is largely achieved by
      disrupting the biofilm to allow regression of inflammation and healing. As our
      patients are living for longer they are likely to have been exposed to systemic
      medications that aim to reduce inflammation. These drugs have been shown to
      decrease inflammation within the periodontal tissues despite not being a primary
      function of their use. This paper aims to review the relative effects of common
      systemic medications on the periodontal tissues by analyzing their modes of
      action and discussing current research and the implications for periodontal
      treatment.

PMID- 24320965
TI  - Targeting receptor tyrosine kinase MET in cancer: small molecule inhibitors and
      clinical progress.
AB  - The HGF/MET signaling pathway is critical in mediating a wide range of normal
      physiological functions including embryological development, wound healing, and
      tissue regeneration. Aberrant activation of the pathway has frequently been found
      in human cancers via protein overexpression, mutation, gene amplification, and
      also paracrine or autocrine up-regulation. In addition, the activation of HGF/MET
      signaling confers resistance to the effects of cancer treatments. Therefore,
      inhibition of the HGF/MET signaling pathway has great potential for therapeutic
      intervention in cancer. Currently, there are three approaches toward modulating
      HGF/MET signaling in human clinical studies of cancer: anti-HGF monoclonal
      antibodies, MET monoclonal antibodies, and small molecule MET inhibitors.
      Preliminary clinical benefit from inhibition of HGF or MET has been reported.
      This Perspective will provide an overview of the HGF/MET signaling pathway in
      cancer and then will review the development of small molecule MET inhibitors and
      their progress in clinical applications. 

PMID- 24320966
TI  - Histopathological study of cutaneous manifestations in HIV and AIDS patients.
AB  - OBJECTIVES: Most human immunodeficiency virus (HIV)-infected patients develop
      various skin diseases. These skin manifestations not only act as markers but also
      reflect the patient's underlying immune status. Investigating CD4 counts is
      costly and not always possible. Thus, the potential value to be gained by using
      skin manifestations as predictors of low CD4 counts and disease progression
      should be explored. The present study attempted to correlate the association of
      various cutaneous disorders found in HIV patients with CD4 and CD8 counts, the
      CD4 : CD8 ratio and stage of HIV infection. METHODS: This was a prospective study
      involving 61 patients who were HIV-positive and demonstrated skin lesions. Punch
      biopsies of skin were taken for histopathological diagnosis. CD4 and CD8 T cell
      counts were performed. RESULTS: The study sample included a majority of male
      patients, most of whom were aged 21-40 years. Pruritic papular dermatitis was the
      most common skin manifestation, followed by molluscum contagiosum, eosinophilic
      folliculitis, and Hansen's disease. Most of the lesions were associated with CD4
      counts of <220/MUl (n = 38). All skin lesions associated with HIV or acquired
      immune deficiency syndrome (AIDS) showed a CD4 : CD8 ratio of <0.50. CONCLUSIONS:
      The study findings demonstrate an inverse relationship between CD4 counts and the
      occurrence of skin lesions. The majority of lesions were associated with stage 3
      or stage 4 infection. Thus, specific cutaneous manifestations can be considered
      as good clinical indicators for predicting underlying immune status in resource
      poor countries.

PMID- 24320967
TI  - Challenges in predicting which oral mucosal potentially malignant disease will
      progress to neoplasia.
AB  - Probably the greatest challenge to those managing patients with oral diseases is
      the dilemma of attempting to predict which oral erythroplakias, leukoplakias,
      lichenoid and other potentially malignant mucosal disease (PMD) such as oral
      submucous fibrosis will progress to neoplasia--notably oral squamous cell
      carcinoma (OSCC). The paper reviews progress over the past decade and the
      application to the clinical situation.

PMID- 24320968
TI  - Urban legend series: mucous membrane pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune
      subepithelial blistering diseases affecting primarily mucous membranes showing
      marked degree of clinical and immunological variability. We investigated four
      controversial topics: (i) Does oral pemphigoid (OP) really exist as a separate
      entity? (ii) Is mucous membrane pemphigoid curable? (iii) What is the best
      therapeutic option for MMP? (iv) Does exclusive oral IgA dermatitis exist as a
      distinct entity from MMP? Results from extensive literature searches suggested
      that (i) it is still unclear whether patients with OP could be considered as a
      distinct subset of MMP with specific clinical and immunological features; (ii) it
      is uncertain whether treatment regimens that get MMP under control can be
      eliminated to allow patients to be in drug-free remission or they should be
      continuously administered in some capacities; (iii) there is a concerning paucity
      of good-quality trials on MMP and available recommendations are solely based on
      generally small patients' cohorts or case series. Some of the 2002 consensus
      experts' opinions should be possibly updated, particularly regarding the safety
      of sulfa drugs; (iv) we did not find any strong evidence to support an exclusive
      oral (and perhaps also mucosal) form of LAD as a separate entity. 

PMID- 24320969
TI  - Control of metal catalyst selectivity through specific noncovalent molecular
      interactions.
AB  - The specificity of chemical reactions conducted over solid catalysts can
      potentially be improved by utilizing noncovalent interactions to direct reactant
      binding geometry. Here we apply thiolate self-assembled monolayers (SAMs) with an
      appropriate structure to Pt/Al2O3 catalysts to selectively orient the reactant
      molecule cinnamaldehyde in a configuration associated with hydrogenation to the
      desired product cinnamyl alcohol. While nonspecific effects on the surface active
      site were shown to generally enhance selectivity, specific aromatic stacking
      interactions between the phenyl ring of cinnamaldehyde and phenylated SAMs
      allowed tuning of reaction selectivity without compromising the rate of desired
      product formation. Infrared spectroscopy showed that increased selectivity was a
      result of favorable orientation of the reactant on the catalyst surface. In
      contrast, hydrogenation of an unsaturated aldehyde without a phenyl ring showed a
      nontunable improvement in selectivity, indicating that thiol SAMs can improve
      reaction selectivity through a combination of nonspecific surface effects and
      ligand-specific near-surface effects. 

PMID- 24320970
TI  - Lung-protective ventilation in emergency department patients with severe sepsis.

PMID- 24320972
TI  - Outer membrane protein assembly factor YaeT (omp85) and GroEL proteins of
      Edwardsiella tarda are immunogenic antigens for Labeo rohita (Hamilton).

PMID- 24320973
TI  - POEMS syndrome with an unusual dermatologic manifestation: immunopathology of
      skin lesions.

PMID- 24320974
TI  - Red cell distribution width is associated with long-term prognosis in patients
      with stable coronary artery disease.
AB  - BACKGROUND: Data regarding the association between red cell distribution width
      (RDW) values and mortality in patients with stable coronary artery disease are
      scarce. We aimed to investigate the link between mortality and RDW in patients
      with stable coronary artery disease undergoing percutaneous coronary intervention
      (PCI). METHODS: We analyzed 2550 consecutive patients with stable coronary artery
      disease who underwent PCI between 2007 and 2011 at our institution. The patients
      were divided into four groups according to RDW quartiles. The association between
      the RDW values and the outcomes was assessed using Cox proportional regression
      analysis after adjusting for clinical, echocardiographic, hemodynamic and
      laboratory data in the whole population and in subgroups stratified by gender,
      presence of diabetes, anemia or heart failure. RESULTS: In the entire population,
      there was a stepwise relationship between RDW intervals and comorbidities.
      Patients with the highest RDW values were older and more often burdened with
      diabetes, heart failure and chronic kidney disease. There was an almost 4-fold
      increase in mortality during an average of 2.5 years of follow-up between the
      group of patients with RDW values lower than 13.1% (25th percentile) and the
      group with RDW values higher than 14.1% (75th percentile), (4.3% vs. 17.1%, p <
      0.0001). After adjusting for the covariates, RDW remained significantly
      associated with mortality in the whole cohort (HR-1.23 [95% CI (1.13-1.35), p <
      0.0001]) and in the subgroups stratified by gender, age (over and under 75
      years), presence of anemia, diabetes, heart failure and chronic kidney disease.
      CONCLUSION: Higher RDW values correspond to higher comorbidity burdens and higher
      mortality. RDW is an independent predictor of mortality in patients with stable
      coronary artery disease.

PMID- 24320975
TI  - One-step fabrication of self-assembled peptide thin films with highly dispersed
      noble metal nanoparticles.
AB  - Fabrication of organic thin films with highly dispersed inorganic nanoparticles
      is a very challenging topic. In this work, a new approach that combines electron
      induced molecular self-assembly with simultaneous nanoparticle formation by room
      temperature electron reduction was developed to prepare peptide thin films with
      highly dispersed noble metal nanoparticles. Argon glow discharge was employed as
      the resource of electrons. The peptide motif KLVFF (Abeta16-20) self-assembled
      into two-dimensional membranes under the influence of hydrated electrons, while
      the metal ions in solution can be simultaneously reduced by electrons to form
      nanoparticles. Our TEM imaging reveals that metal nanoparticles were well
      distributed in the resulting peptide thin films. Our results also suggest that
      the size of metal nanoparticles can be tuned by varying the initial concentration
      of the metal ion. This simple approach can be viewed as a promising strategy to
      create hybrid thin films that integrate functional inorganics into biomolecule
      scaffolds. 

PMID- 24320976
TI  - Nursing in the 21st century: is there a place for nursing philosophy?

PMID- 24320977
TI  - Three dialogues concerning robots in elder care.
AB  - The three dialogues in this contribution concern 21st century application of life
      like robots in the care of older adults. They depict conversations set in the
      near future, involving a philosopher (Dr Phonius) and a nurse (Dr Myloss) who
      manages care at a large facility for assisted living. In their first dialogue,
      the speakers discover that their quite different attitudes towards human-robot
      interaction parallel fundamental differences separating their respective concepts
      of consciousness. The second dialogue similarly uncovers deeply contrasting
      notions of personhood that appear to be associated with respective communities of
      nursing and robotics. The additional key awareness that arises in their final
      dialogue links applications of life-like robots in the care of older adults with
      potential transformations in our understandings of ourselves - indeed, in our
      understandings of the nature of our own humanity. This series of dialogues,
      therefore, appears to address a topic in nursing philosophy that merits our
      careful attention. 

PMID- 24320978
TI  - The nature of reality represented in high fidelity human patient simulation:
      philosophical perspectives and implications for nursing education.
AB  - Simulation technology is increasingly being used in nursing education. Previously
      used primarily for teaching procedural, instrumental, or critical incident types
      of skills, simulation is now being applied to training related to more dynamic,
      complex, and interpersonal human contexts. While high fidelity human patient
      simulators have significantly increased in authenticity, human responses have
      greater complexity and are qualitatively different than current technology
      represents. This paper examines the texture of representation by simulation.
      Through a tracing of historical and contemporary philosophical perspectives on
      simulation, the nature and limits of the reality of human health responses
      represented by high fidelity human patient simulation (HF-HPS) are explored.
      Issues concerning nursing education are raised around the nature of reality
      represented in HF-HPS. Drawing on Waks, a framework for guiding pedagogical
      considerations around simulation in nursing education is presented for the
      ultimate purpose of promoting an educative experience with simulation. 

PMID- 24320979
TI  - What is nursing in the 21st century and what does the 21st century health system
      require of nursing?
AB  - It is frequently claimed that nursing is vital to the safe, humane provision of
      health care and health service to our populations. It is also recognized however,
      that nursing is a costly health care resource that must be used effectively and
      efficiently. There is a growing recognition, from within the nursing profession,
      health care policy makers and society, of the need to analyse the contribution of
      nursing to health care and its costs. This becomes increasingly pertinent and
      urgent in a situation, such as that existing in Ireland, where the current
      financial crisis has lead to public sector employment moratoria, staff cuts and
      staffing deficits, combined with increased patient expectation, escalating health
      care costs, and a health care system restructuring and reform agenda. Such
      factors, increasingly common internationally, make the identification and
      effective use of the nursing contribution to health care an issue of
      international importance. This paper seeks to explore the nature of nursing and
      the function of the nurse within a 21st century health care system, with a focus
      on the Irish context. However, this analysis fits into and is relevant to the
      international context and discussion regarding the nursing workforce. This paper
      uses recent empirical studies exploring the domains of activity and focus of
      nursing, together with nurses perceptions of their role and work environment, in
      order to connect those findings with core conceptual questions about the nature
      and function of nursing. 

PMID- 24320971
TI  - Skeletal muscle tissue engineering: methods to form skeletal myotubes and their
      applications.
AB  - Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective
      skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular
      disease. However, two decades after the introduction of SMTE, the engineering of
      functional skeletal muscle in the laboratory still remains a great challenge, and
      numerous techniques for growing functional muscle tissues are constantly being
      developed. This article reviews the recent findings regarding the methodology and
      various technical aspects of SMTE, including cell alignment and differentiation.
      We describe the structure and organization of muscle and discuss the methods for
      myoblast alignment cultured in vitro. To better understand muscle formation and
      to enhance the engineering of skeletal muscle, we also address the molecular
      basics of myogenesis and discuss different methods to induce myoblast
      differentiation into myotubes. We then provide an overview of different coculture
      systems involving skeletal muscle cells, and highlight major applications of
      engineered skeletal muscle tissues. Finally, potential challenges and future
      research directions for SMTE are outlined. 

PMID- 24320980
TI  - Nursing and human freedom.
AB  - Debates over how to conceptualize the nursing role were prominent in the nursing
      literature during the latter part of the twentieth century. There were, broadly,
      two schools of thought. Writers like Henderson and Orem used the idea of a self
      care deficit to understand the nurse as doing for the patient what he or she
      could not do alone. Later writers found this paternalistic and emphasized the
      importance of the patient's free will. This essay uses the ideas of positive and
      negative freedom to explore the differing conceptions of autonomy which are
      implicit in this debate. The notion of positive freedom has often been criticized
      as paternalistic, and the criticisms of self-care in the nursing literature echo
      criticisms from political philosophy. Recent work on relational autonomy and on
      the relationship between autonomy and identity are used to address these
      objections. This essay argues for a more nuanced conception of the obligation to
      support autonomy that includes both positive (freedom to) and negative (freedom
      from) dimensions. This conception of autonomy provides a moral foundation for
      conceptualizing nursing in something like Henderson's terms: as involving the
      duty to expand the patient's capacities. The essay concludes by generalizing the
      lesson. Respect for autonomy on the part of any health care provider requires
      both respect for the patient's choices and a commitment to expand the patient's
      ability to actualize their choices. 

PMID- 24320981
TI  - Contemporary nursing wisdom in the UK and ethical knowing: difficulties in
      conceptualising the ethics of nursing.
AB  - This paper's philosophical ideas are developed from a General Nursing Council for
      England and Wales Trust-funded study to explore nursing knowledge and wisdom and
      ways in which these can be translated into clinical practice and fostered in
      junior nurses. Participants using Carper's (1978) ways of knowing as a framework
      experienced difficulty conceptualizing a link between the empirics and ethics of
      nursing. The philosophical problem is how to understand praxis as a moral entity
      with intrinsic value when so much of value seems to be technical and extrinsic
      depending on desired ends. Using the Aristotelian terms poesis and praxis can
      articulate the concerns that the participants as well as Carper (1978) and
      Dreyfus (in Flyvbjerg, 1991) among others share that certain actions or ways of
      knowing important for nursing are being devalued and deformed by the importance
      placed on quantitative data and measurable outcomes. The sense of praxis is a
      moralized one and most of what nurses do is plausibly on any account of normative
      ethics a morally good thing; the articulation of the idea of praxis can go some
      way in showing how it is a part of the discipline of nursing. Nursing's acts as
      poesis can be a part of how practitioners come to have praxis as phronesis or
      practical wisdom. So to be a wise nurse, one needs be a wise person. 

PMID- 24320982
TI  - Is there nursing phenomenology after Paley? Essay on rigorous reading.
AB  - At the bedside, nurses are expected to be precise when they read indications on
      screens and on the bodies of patients and decide on the meaning of words framed
      by the context of acute care. In academia, although there is no incident report
      to fill when we misread or misrepresent complex philosophical ideas, the
      consequences of inaccurate reading include misplaced epistemological claims and
      poor scholarship. A long and broad convention of nursing phenomenological
      research, in its various forms, claims a philosophical grounding in the ideas of
      Husserl, Heidegger, and other thinkers. But for nearly two decades, nurse
      phenomenologists' knowledge claims have been challenged by well-informed
      criticisms, most notably by John Paley. At the heart of criticism lies an
      observation that Continental phenomenological thought is misrepresented in many
      nursing sources and that nursing phenomenology, both descriptive and
      interpretive, cannot appeal to the authority of either Husserl or Heidegger.
      Taking these criticisms seriously, I am asking, Is phenomenology after Paley
      possible? If misreading seems to be an issue, how can - or should - we read
      rigorously? My thinking through these questions is influenced by the ideas of
      Jacques Derrida. Under a condition of a play of language, of Derridian
      differance, when meaning is never self-identical and never fully arrives, I
      suggest that one has to negotiate meanings through reading for differences. I
      develop this idea in relation to the methodological conventions of
      phenomenological nursing research and argue for a careful rereading of the whole
      field of phenomenological nursing research. Such rereading presupposes and
      necessitates interdisciplinary engagement between nursing and the humanities and
      interpretive social sciences. Greater familiarity with research practices of
      those disciplines that stress theoretical and writing rigour might make visible
      the limits of nursing research approaches and their quality criteria. An
      understanding of philosophical and theoretical works - a condition of quality
      scholarship - depends on our reading of both originary texts and contemporary
      literature from the humanities and the social sciences. This understanding, far
      from obliging researchers to always trace (often erroneously) their work to its
      philosophical roots, opens other, often more sound, methodological possibilities.

PMID- 24320983
TI  - Domesticating Paley: how we misread Paley (and phenomenology).

PMID- 24320984
TI  - Effect of self-association of bovine serum albumin on the stability of surfactant
      induced aggregates of allylamine-capped silicon quantum dots.
AB  - The concentration-dependent self-association of bovine serum albumin (BSA) and
      subsequent altered interaction with sodium dodecyl sulfate (SDS) has been
      explored by means of photoluminescence (PL) spectroscopy, dynamic light
      scattering (DLS), circular dichroism (CD), PL imaging, and atomic force
      microscopy (AFM). By using an extrinsic luminescent probe, allylamine-capped
      silicon quantum dots (Si-QDs), we have demonstrated the unusual concentration
      dependent altered BSA-SDS interaction. Allylamine-capped Si-QDs forms ordered
      aggregates in the presence of 1 mM SDS due to hydrogen bonding with the
      surfactants head groups at pH 7.4. Although these aggregates remain stable in the
      presence of monomeric BSA in the concentration range 1-8 MUM, they form typical
      ring-shaped doughnut-like structures due to "necklace and bead"-like complex
      formation. However, beyond 10 MUM BSA, these aggregates of Si-QDs slowly
      dissociate and complete dissociation occurs at 150 MUM BSA. These anomalous
      results have been explained by considering the altered hydrophilicity of self
      associated BSA. 

PMID- 24320985
TI  - Analysis of fatty acids, aliphatic esters, and in vitro studies of antioxidant
      and antimicrobial activities for Recineckea carnea and Tupistra chinensis from
      the Guizhou Province.
AB  - Recineckea carnea and Tupistra chinensis collected from the Guizhou province
      (China) were evaluated in this study. Petroleum ether fractions from the two
      herbs were subjected to gas chromatography-mass spectrometry analysis; 10
      species, which were fatty acids or aliphatic esters, were identified. The
      antimicrobial activities of a variety of extracts were evaluated against four
      microorganisms. The methanol extract (ME), chloroform fraction, and ethyl acetate
      fraction from T. chinensis exhibited antimicrobial activities comparable to
      standard antibiotics, whereas none of the investigated extracts from R. carnea
      demonstrated any antimicrobial activities. The antioxidant potential was
      evaluated in vitro using ferric-reducing antioxidant power (FRAP) and the 2,2
      diphenyl-1-picrylhydrazil (DPPH) radical method. The FRAP value of the ME from T.
      chinensis (4.19+/-0.088 mmol/g) was found to be significantly higher than the
      analogous extract from R. carnea (2.39+/-0.092 mmol/g); the EC50 of the ME from
      R. carnea (0.32+/-0.011 mg/mL) was found to be significantly higher than that of
      T. chinensis (0.30+/-0.015 mg/mL). Total phenolic content was estimated by the
      Folin-Ciocalteu's colorimetric method. A positive correlation was found between
      total phenolic content and antioxidant activities (FRAP value and the reciprocal
      of EC50). The results suggested that the phenolic compounds contributed
      significantly to the antioxidant capacity of R. carnea and T. chinensis.

PMID- 24320986
TI  - Essential oil composition and antibacterial activity of Origanum vulgare subsp.
      glandulosum Desf. at different phenological stages.
AB  - Variation in the quantity and quality of the essential oil (EO) of wild
      population of Origanum vulgare at different phenological stages, including
      vegetative, late vegetative, and flowering set, is reported. The oils of air
      dried samples were obtained by hydrodistillation. The yield of oils (w/w%) at
      different stages were in the order of late vegetative (2.0%), early vegetative
      (1.7%), and flowering (0.6%) set. The oils were analyzed by gas chromatography
      (GC) and GC-mass spectrometry (GC-MS). In total, 36, 33, and 16 components were
      identified and quantified in vegetative, late vegetative, and flowering set,
      representing 94.47%, 95.91%, and 99.62% of the oil, respectively. Carvacrol was
      the major compound in all samples. The ranges of major constituents were as
      follows: carvacrol (61.08-83.37%), p-cymene (3.02-9.87%), and gamma-terpinene
      (4.13-6.34%). Antibacterial activity of the oils was tested against three Gram
      positive and two Gram-negative bacteria by the disc diffusion method and
      determining their diameter of inhibition and the minimum inhibitory concentration
      (MIC) values. The inhibition zones and MIC values for bacterial strains, which
      were sensitive to the EO of O. vulgare subsp. glandulosum, were in the range of 9
      36 mm and 125-600 MUg/mL, respectively. The oils of various phenological stages
      showed high activity against all tested bacteria, of which Bacillus subtilis was
      the most sensitive and resistant strain, respectively. Thus, they represent an
      inexpensive source of natural antibacterial substances that exhibited potential
      for use in pathogenic systems.

PMID- 24320987
TI  - Effects of porcine hemoglobin on serum lipid content and fecal lipid excretion in
      rats.
AB  - The purpose of this study was to elucidate the effects of dietary hemoglobin on
      serum and liver lipid contents in rats, and the ability of hemoglobin
      hydrolysates to disrupt lipid absorption. After rats had been fed on casein- or
      porcine hemoglobin-containing diets for 4 weeks, their serum and liver lipid
      contents and fecal cholesterol, bile acid, and nitrogen excretion were measured.
      To elucidate the mechanism of lipid absorption by dietary hemoglobin, we also
      examined lipase activity, micellar solubility of cholesterol, and bile acid
      binding activity in the presence of hemoglobin hydrolysates. Dietary hemoglobin
      decreased serum and liver triglyceride and cholesterol contents and increased
      fecal fatty acid, cholesterol, and bile acid excretion. In addition, hemoglobin
      hydrolysates inhibited lipase activity compared with casein hydrolysates in an in
      vitro study. These results suggested that the hypolipidemic effect of hemoglobin
      is mediated by increased fecal lipid excretion, and that decreased lipase
      activity by hemoglobin is at least partially responsible for this result. The
      observed effects were documented with an 8 g/kg hemoglobin diet, which is lower
      than in other studies; therefore. hemoglobin may be useful in the prevention of
      lifestyle-related diseases.

PMID- 24320988
TI  - A-1012G promoter polymorphism of vitamin D receptor gene is associated with
      psoriasis risk and lower allele-specific expression.
AB  - Psoriasis is caused by a combination of genetic, immunologic, and environmental
      factors. The vitamin D receptor (VDR) is involved in antiproliferative and
      prodifferentiation pathways in keratinocytes and exerts immunosuppressive
      effects. We aimed to investigate possible associations between VDR polymorphisms
      and psoriasis susceptibility and to evaluate functional effects of potential
      psoriasis-associated polymorphisms. We genotyped 108 patients with psoriasis and
      268 healthy controls at 5 VDR polymorphisms (A-1012G, FokI, BsmI, ApaI, and TaqI)
      by TaqMan allelic-discrimination real-time polymerase chain reaction. We found a
      significant increased overall risk of psoriasis for the VDR A-1012G promoter
      polymorphism (odds ratio [OR]=2.43, 95% confidence interval [CI]: 1.15-5.13;
      p=0.05). A significant higher frequency (p=0.035) of the A allele was found in
      psoriatic cases compared with controls. In a case-case analysis, a statistically
      significant association between A-1012G and family history emerged (p=0.033).
      Furthermore, a significant association of A-1012G risk genotypes with a lower
      expression of VDR mRNA emerged (p=0.0028). Our data show that VDR promoter A
      1012G polymorphism is associated with psoriasis risk and suggest that this
      polymorphism may modulate psoriasis risk by affecting VDR expression.

PMID- 24320989
TI  - Ecology drives intragenomic conflict over menopause.
AB  - Menopause is the transition from reproductive to non-reproductive life well
      before natural death. Rather than involving a smooth, rapid change, it is
      normally preceded by a long period of erratic hormonal fluctuation that is
      accompanied by a plethora of unpleasant symptoms. Here, we (1) suggest that this
      turbulent period owes to conflict, between a woman's maternally inherited (MI)
      and paternally inherited (PI) genes, over the trade-off between reproduction and
      communal care; (2) perform a theoretical analysis to show that this conflict is
      resolved either through silencing or fluctuating expression of one of the genes;
      (3) highlight which of the symptoms preceding menopause may result from
      antagonistic co-evolution of MI and PI genes; (4) argue that ecological
      differences between ancestral human populations may explain the variability in
      menopause among different ethnic groups; (5) discuss how these insights may be
      used to inform family planning and cancer risk assessment based on a woman's
      ancestral background. 

PMID- 24320990
TI  - Perioperative corticosteroids administration as a risk factor for pressure ulcers
      in cardiovascular surgical patients: a retrospective study.
AB  - The aim of this study was to investigate the relationship between perioperative
      corticosteroids administration and the incidence of pressure ulcers (PUs) in
      cardiovascular surgical patients. A retrospective analysis was performed on data
      from consecutive patients who had cardiac surgery in 2012. Univariate and
      multivariate logistic regression analyses were performed to evaluate the
      relationship between perioperative corticosteroid administration and the
      incidence of surgery-related PU (SRPU). A total of 286 cardiac surgery patients
      were included in this study; of these, 47 patients developed 57 SRPUs, an
      incidence of 16.4% [95% confidence interval (CI): 12.3-21.2%). The SRPU incidence
      was significantly higher in corticosteroid-administered group compared with
      groups not receiving corticosteroids (43.8% versus 14.8%, Pearson's chi(2)  =
      9.209, P = 0.002). The crude odds ratio (OR) was 4.472 (95% CI: 1.576-12.694).
      After performing multivariate logistic regression analysis, the adjusted OR was
      2.808 (95% CI: 1.062-11.769). This result showed that perioperative
      corticosteroid administration was an independent risk factor for PUs in
      cardiovascular surgical patients. Therefore, it is recommended that in order to
      prevent PU perioperative corticosteroids should be administered with caution to
      cardiovascular surgical patients. 

PMID- 24320991
TI  - Ce-doped YAG nanophosphor and red emitting CuInS2/ZnS core/shell quantum dots for
      warm white light-emitting diode with high color rendering index.
AB  - In this work, we report the solvothermal synthesis of Ce-doped YAG (YAG:Ce)
      nanoparticles (NPs) and their association with a free-Cd CuInS2/ZnS (CIS/ZnS)
      core/shell QDs for application into white light emitting diode (WLED). 1500 
      degrees C-annealed YAG:Ce NPs and CIS/ZnS core/shell QDs exhibited intense yellow
      and red emissions band with maxima at 545 and 667 nm, respectively. Both YAG:Ce
      nanophosphor and CIS/ZnS QDs showed high photoluminescence quantum yield (PL QY)
      of about 50% upon 460 nm excitation. YAG:Ce nanophosphor layer and bilayered
      YAG:Ce nanophosphor-CIS/ZnS QDs were applied on blue InGaN chip as converter
      wavelength to achieve WLED. While YAG:Ce nanophosphor converter layer showed low
      color rendering index (CRI) and cold white light, bilayered YAG:Ce nanophosphor
      CIS/ZnS QDs displayed higher CRI of about 84 and warm white light with a
      correlated color temperature (CCT) of 2784 K. WLED characteristics were measured
      as a function of forward current from 20 to 1200 mA. The white light stability of
      bilayered nanophosphor-QDs-based WLED operated at 200 mA was also studied as a
      function of operating time up to 40 h. Interestingly, CRI and CCT of such device
      tend to remain constant after 7 h of operating time suggesting that layer-by
      layer structure of YAG:Ce phosphor and red-emitting CIS/ZnS QDs could be a good
      solution to achieve stable warm WLED, especially when high current density is
      applied. 

PMID- 24320992
TI  - The effects of clinical and statistical heterogeneity on the predictive values of
      results from meta-analyses.
AB  - Variance between studies in a meta-analysis will exist. This heterogeneity may be
      of clinical, methodological or statistical origin. The last of these is
      quantified by the I(2) -statistic. We investigated, using simulated studies, the
      accuracy of I(2) in the assessment of heterogeneity and the effects of
      heterogeneity on the predictive value of meta-analyses. The relevance of
      quantifying I(2) was determined according to the likely presence of heterogeneity
      between studies (low, high, or unknown) and the calculated I(2) (low or high).
      The findings were illustrated by published meta-analyses of selective digestive
      decontamination and weaning protocols. As expected, I(2) increases and the
      likelihood of drawing correct inferences from a meta-analysis decreases with
      increasing heterogeneity. With low levels of heterogeneity, I(2) does not appear
      to be predictive of the accuracy of the meta-analysis result. With high levels of
      heterogeneity, even meta-analyses with low I(2) -values have low predictive
      values. Most commonly, the level of heterogeneity in a meta-analysis will be
      unknown. In these scenarios, I(2) determination may help to identify estimates
      with low predictive values (high I(2) ). In this situation, the results of a meta
      analysis will be unreliable. With low I(2) -values and unknown levels of
      heterogeneity, predictive values of pooled estimates may range extensively, and
      findings should be interpreted with caution. In conclusion, quantifying
      statistical heterogeneity through I(2) -statistics is only helpful when the
      amount of clinical heterogeneity is unknown and I(2) is high. Objective methods
      to quantify the levels of clinical and methodological heterogeneity are urgently
      needed to allow reliable determination of the accuracy of meta-analyses. 

PMID- 24320993
TI  - Sesquiterpene lactones from Ferula oopoda and their cytotoxic properties.
AB  - Two new sesquiterpene lactones, namely feruhodin A and feruhodin B, together with
      six known compounds, daucoeudesmanolactone, dehydrooopodin, oopodin, badkhysin, 7
      demethylplastochromenol, and scoparone, were isolated from the roots of Ferula
      oopoda. The structures of these compounds were elucidated by 1D and 2D NMR
      techniques as well as high-resolution mass spectrometry. Cytotoxic effects of
      these compounds were evaluated against two human cancer cell lines including
      MCF7and K562 using the Alamar blue assay. The results showed that dehydrooopodin
      possessed significant cytotoxic effects with IC50 values of 15 and 5 MUM against
      MCF7 and K562, respectively.

PMID- 24320995
TI  - Infection with bacteroides thetaiotaomicron during posterior decompression and
      dynamic stabilization of the lumbar spine: a case report and review of the
      literature.
AB  - Patient and surgical risk factors have often been implicated for postoperative
      posterior spinal wound infection. A 56-year-old male with widely disseminated
      multiple myeloma presented with severe back pain and lower extremity weakness as
      a result of fracture and collapse of the L4 vertebral body. Posterior
      decompression involving bilateral pedicle resection and partial L4 corpectomy was
      performed. Stabilization was performed by Dynesys instrumentation of L3-5, screw
      supplementation with polymethylmethacrylate, and posterolateral fusion was
      performed. Postoperatively, the patient suffered from multiple infections,
      including Bacteroides thetaiotaomicron, which were eventually resolved with
      antibiotic as well as incision and debridement treatment regimens. In cases with
      numerous perioperative risk factors for infections, the best therapeutic approach
      may be a preventative one. An understanding of the relevant risk factors may
      enable the physician to facilitate a perioperative condition best suited for
      optimal treatment. A case report of infection with Bacteroides thetaiotaomicron
      during lumbar decompression and dynamic stabilization as well as a review of the
      literature regarding infection risk factors are presented.

PMID- 24320994
TI  - Guidelines for establishing a telemental health program to provide evidence-based
      therapy for trauma-exposed children and families.
AB  - Although similar rates of traumatic experiences exist in both rural and urban
      settings, mental health resources available to those living in rural areas are
      often scarce. Limited resources pose a problem for children and families living
      in rural areas, and several barriers to service access and utilization exist
      including reduced anonymity, few "after hours" services, decreased availability
      of evidence-based treatments, few specialty clinics, and expenses associated with
      travel, taking time off work, and provision of childcare. As a solution, the
      authors discuss the utility, use, and set-up of a telemental health program
      within an existing community outreach program. Suggestions for establishing a
      telemental health clinic are presented along with guidelines for the delivery of
      trauma-focused, cognitive-behavioral therapy (TF-CBT) via telemental health
      videoconferencing technology. Specific guidelines discussed include (1)
      establishing and using community partnerships, (2) Memoranda of Understanding
      (MOU), (3) equipment setup and technological resources, (4) videoconferencing
      software, (5) physical setup, (6) clinic administration, (7) service
      reimbursement and start-up costs, (8) therapy delivery modifications, and (9)
      delivering culturally competent services to rural and remote areas.

PMID- 24320996
TI  - Protein dynamics are influenced by the order of ligand binding to an antibiotic
      resistance enzyme.
AB  - The aminoglycoside N3 acetyltransferase-IIIb (AAC) is responsible for conferring
      bacterial resistance to a variety of aminoglycoside antibiotics. Nuclear magnetic
      resonance spectroscopy and dynamic light scattering analyses revealed a
      surprising result; the dynamics of the ternary complex between AAC and its two
      ligands, an antibiotic and coenzyme A, are dependent upon the order in which the
      ligands are bound. Additionally, two structurally similar aminoglycosides,
      neomycin and paromomycin, induce strikingly different dynamic properties when
      they are in their ternary complexes. To the best of our knowledge, this is the
      first example of a system in which two identically productive pathways of forming
      a simple ternary complex yield significant differences in dynamic properties.
      These observations emphasize the importance of the sequence of events in
      achieving optimal protein-ligand interactions and demonstrate that even a minor
      difference in molecular structure can have a profound effect on biochemical
      processes. 

PMID- 24320997
TI  - Synergistic Au/Ga catalysis in ambient Nakamura reaction.
AB  - The gold-catalyzed intermolecular addition of 1,3-dicarbonyl compounds to
      unactivated 1-alkynes (Nakamura reaction) is achieved at room temperature for the
      first time through synergistic gold/gallium catalysis. The developed system is
      highly efficient with a gold catalyst loading that can be as low as 500 ppm. 

PMID- 24320998
TI  - Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists
      resulting in a clinical candidate for the treatment of cancer (AZD5582).
AB  - A series of dimeric compounds based on the AVPI motif of Smac were designed and
      prepared as antagonists of the inhibitor of apoptosis proteins (IAPs).
      Optimization of cellular potency, physical properties, and pharmacokinetic
      parameters led to the identification of compound 14 (AZD5582), which binds
      potently to the BIR3 domains of cIAP1, cIAP2, and XIAP (IC50 = 15, 21, and 15 nM,
      respectively). This compound causes cIAP1 degradation and induces apoptosis in
      the MDA-MB-231 breast cancer cell line at subnanomolar concentrations in vitro.
      When administered intravenously to MDA-MB-231 xenograft-bearing mice, 14 results
      in cIAP1 degradation and caspase-3 cleavage within tumor cells and causes
      substantial tumor regressions following two weekly doses of 3.0 mg/kg.
      Antiproliferative effects are observed with 14 in only a small subset of the over
      200 cancer cell lines examined, consistent with other published IAP inhibitors.
      As a result of its in vitro and in vivo profile, 14 was nominated as a candidate
      for clinical development.

PMID- 24321000
TI  - Access and surgical approach to the isolated intranasal basal cell carcinoma.
AB  - Primary intranasal basal cell carcinoma (BCC) is a rare tumour that presents a
      therapeutic challenge. Here we present two cases illustrating the lateral
      alarotomy to gain access to an isolated BCC involving only the intranasal lining.
      Successful intranasal access was achieved in both cases using the alarotomy
      technique. We also review other methods of repair for the isolated intranasal
      lining defect. The presentation of intranasal BCC purely as an isolated entity
      without cutaneous involvement is rare, and our surgical approach via alarotomy
      allows optimum visibility for tumour resection. 

PMID- 24320999
TI  - The effects of Zumba training on cardiovascular and neuromuscular function in
      female college students.
AB  - The present study examined the effects of Zumba training (group fitness based on
      salsa and aerobics) on endurance, trunk strength, balance, flexibility, jumping
      performance and quality of life (QoL) in female college students. Thirty female
      participants were randomly assigned (strata: age, BMI and physical activity) to
      an intervention (INT, n = 15: age: 21.0 +/- 2.3 years; BMI: 21.8 +/- 3.0 kg/m(2);
      physical activity (PA): 7.6 +/- 4.6 h/week) or control group (CON, n = 14: age:
      21.0 +/- 2.8 years; BMI: 21.0 +/- 2.1 kg/m(2); PA: 7.3 +/- 3.6 h/week).
      Instructed Zumba training was provided twice a week for 8 weeks (training
      attendance: 100%). QoL was assessed using the WHO-QoL-BREF questionnaire.
      Endurance was measured with the 6-min walking test (6MWT). Trunk flexibility was
      assessed with the stand-and-reach-test and lower-extremity strength with the jump
      and-reach-test. The star excursion balance test (SEBT) was employed to assess
      dynamic balance. Trunk strength endurance was examined using the Swiss global
      trunk strength test in prone and lateral (left, right) positions. All testings
      were performed before and after the training period. We observed large
      statistically significant between-group effects of total QoL score (INT: +9.8%,
      CON: +0.4%, p < 0.001; partial eta squared [Formula: see text]), 6MWT distance
      (INT: +21%, CON: -2%, p < 0.001, [Formula: see text]), trunk strength endurance
      (prone, INT: +48%, CON: +11%, p = 0.04, [Formula: see text]; lateral-left, INT:
      +71%, CON: +11%, p = 0.01, [Formula: see text], lateral-right, INT: +54%, CON:
      +11%, p = 0.01, [Formula: see text]) and dynamic balance (all eight reaching
      distances of the SEBT, INT: +11-26%, CON: +1.1-3.8%, 0.001 < p < 0.04, 0.14 <
      [Formula: see text]) with significantly larger improvements for INT. Flexibility
      and jump performance were not relevantly affected (p > 0.05). Instructed Zumba
      training can be applied to improve well-being, aerobic fitness and neuromuscular
      function in female college students.

PMID- 24321001
TI  - Microcystic urothelial carcinoma: morphology, immunohistochemistry and clinical
      behaviour.
AB  - AIMS: To report on the clinicopathological features of 20 cases of microcystic
      urothelial bladder carcinoma. METHODS AND RESULTS: The extent of microcystic
      component varied from 50-100% of the specimens. The cysts were round-oval and of
      varying sizes; the periphery of large cysts was frequently punctuated by many
      smaller cysts. The cysts were lined by urothelial, low columnar cells or by a
      single layer of flattened epithelium of low-intermediate nuclear grade. Focal
      high-grade conventional urothelial carcinoma was present in eight cases.
      Immunohistochemistry demonstrated variable positivity for cytokeratins 7 and 20,
      MUC1, MUC5AC, p63 and GATA3. Extent of expression of Ki67, p53 and p27(kip1)
      ranged from 20-60%, 10-40% and 10-30% of cells, respectively. On follow-up, 11
      patients died of disease at 11-56 months and three patients were alive with
      disease at 26-37 months. Univariate survival analysis showed no differences for
      microcystic carcinoma versus conventional urothelial carcinoma (P = 0.548).
      CONCLUSIONS: Microcystic urothelial carcinoma may pose diagnostic difficulties,
      especially in limited biopsy samples, where it may be mistaken for cystitis
      glandularis or adenocarcinoma of the bladder. Histological features, clinical
      history and appropriate immunohistochemical studies should help to distinguish it
      from its mimics. Aggressiveness seems to be related to higher stage at diagnosis.

PMID- 24321002
TI  - Gastric adenocarcinoma of fundic gland type with unusual behavior.

PMID- 24321003
TI  - New tools for estimating the EMS transport interval: implications for policy and
      patient care.

PMID- 24321004
TI  - Prostate specific antigen testing in family practice: a cross sectional survey of
      self-reported rates of and reasons for testing participation and risk disclosure.
AB  - BACKGROUND: Despite controversy about the benefits of routine prostate specific
      antigen (PSA) testing, rates of participation continue to rise. It is important
      to ensure that men are fully informed about the potential risks associated with
      this test. Little is known about the processes of shared decision making for PSA
      testing in the family practice setting. This study aimed to explore men's
      experiences of PSA testing participation and risk disclosure for PSA testing.
      METHODS: A cross-sectional survey of male family practice attendees aged 40 years
      or older, with no previous history of prostate cancer, between June 2010 and
      November 2011. Questions related to whether participants had undertaken PSA
      testing or discussed this with their doctor over the past 5 years, whether the
      patient or doctor had initiated the discussion, reasons for undergoing testing,
      and whether their doctor had discussed particular risks associated with PSA
      testing. RESULTS: Sixty-seven percent (215/320) of men recalled having a PSA test
      in the past five years. Of the respondents who reported not having a test, 14%
      had discussed it with their doctor. The main reasons for having a PSA test were
      doctor recommendation and wanting to keep up to date with health tests. Thirty
      eight percent or fewer respondents reported being advised of each potential risk.
      CONCLUSIONS: Despite debate over the benefits of routine PSA testing, a high
      proportion of male family practice attendees report undertaking this test. Risks
      associated with testing appear to be poorly disclosed by general practitioners.
      These results suggest the need to improve the quality of informed consent for PSA
      testing in the family practice setting.

PMID- 24321005
TI  - CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of
      infantile spasms.
AB  - OBJECTIVE: Infantile spasms (IS) have poor outcomes and limited treatment
      options, including vigabatrin, a gamma-aminobutyric acid (GABA) aminotransferase
      inactivator. Vigabatrin has been associated with retinal toxicity. A high
      affinity vigabatrin analogue (CPP-115; Catalyst Pharmaceutical Partners, Inc.,
      Coral Gables, FL, U.S.A.) has shown lower risk of retinal toxicity. Here, we test
      the efficacy of CPP-115 in reducing spasms and its tolerability in the multiple
      hit rat model of IS, in which daily vigabatrin reduced spasms for only one day,
      but was not well tolerated. METHODS: Male rats were treated with the protocol of
      the multiple-hit model of IS on postnatal day 3 (PN3). Using a randomized,
      blinded, vehicle-controlled, dose-response study design, CPP-115 (0.1, 1, or 5
      mg/kg intraperitoneally [i.p.]) or vehicle was given daily (PN4-12) or as a
      single injection (PN7) after spasm onset. Intermittent video- or video
      electroencephalography (EEG) monitoring was done. Secondary end points included
      the following: daily weights, survival, performance on open field activity,
      surface righting time, and negative geotaxis (PN3-20), horizontal bar (PN13-20),
      and Barnes maze (PN16-19). Statistics used a linear mixed model of raw or
      normalized log-transformed data, taking into account the repeated observations on
      each animal. RESULTS: The lower CPP-115 doses (0.1-1 mg/kg/day, PN4-12) reduced
      spasms between PN6 and 7 without increasing mortality. CPP-115 at 5 mg/kg/day
      (PN4-12) reduced spasms earlier (PN5), but was eventually lethal. A single CPP
      115 injection (1 mg/kg, i.p.) decreased electroclinical spasms acutely but
      transiently. CPP-115 transiently improved the probability to >50% reduction of
      spasms, but did not accelerate spasm cessation. CPP-115 did not alter
      neurodevelopmental outcomes or visuospatial learning. SIGNIFICANCE: We provide
      proof-of-concept evidence that CPP-115, a vigabatrin analogue, decreases spasms
      in the multiple-hit rat model of IS at considerably lower and better tolerated
      doses than vigabatrin did in our previous studies. Further optimization of the
      treatment protocol is needed. CPP-115 may be a promising new candidate treatment
      for IS with better tolerability than vigabatrin.

PMID- 24321007
TI  - Gestational weight gain in relation to offspring obesity over the life course: a
      systematic review and bias-adjusted meta-analysis.
AB  - Gestational weight gain (GWG) is considered one of the risk factors for future
      obesity in the offspring. However, the direction and strength of this association
      at different periods of offspring life is relatively unknown. This study
      investigates whether excess or inadequate maternal GWG during pregnancy
      influences the risk of offspring obesity at different stages in life. A
      systematic review of published articles was undertaken after a comprehensive
      search of different databases, and extracted data were meta-analysed. To quantify
      offspring obesity estimates in relation to GWG, we stratified obesity estimates
      within three life stages of the offspring age: <5 years, 5 to <18 years and 18+
      years. Our meta-analysis showed that, compared with offspring of women with
      adequate GWG, offspring of women who gained inadequate gestational weight were at
      a decreased risk of obesity (relative risk [RR]: 0.86; 95% confidence interval
      [CI]: 0.78-0.94), and offspring of women who gained excess weight were at an
      increased risk of obesity (RR: 1.40; 95% CI: 1.23-1.59). These relationships were
      similar after stratification by life stage. Findings of this study therefore
      suggest that excess GWG does influence offspring obesity over the short- and long
      term, and should therefore be avoided. 

PMID- 24321006
TI  - Parental monitoring trajectories and gambling among a longitudinal cohort of
      urban youth.
AB  - AIM: To test the strength of the association between parental monitoring
      trajectories throughout early adolescence (ages 11-14) and gambling behaviours by
      young adulthood (age 22). DESIGN: Longitudinal cohort design. SETTING: Baltimore,
      Maryland. PARTICIPANTS: The sample of 514 participants with gambling data between
      ages 16-22 and parental monitoring data between ages 11-14 were predominantly
      African American and received subsidized lunches at age 6. MEASUREMENTS: The
      South Oaks Gambling Screen and South Oaks Gambling Screen-Revised for Adolescents
      collected self-reports on annual gambling and gambling problems between ages 16
      22. The Parental Monitoring Subscale of the Structured Interview of Parent
      Management Skills and Practices-Youth Version collected self-reports on annual
      parental monitoring between ages 11-14. FINDINGS: General growth mixture
      modelling identified two parental monitoring trajectories: (i) 'stable' class
      (84.9%) began with a high level of parental monitoring at age 11 that remained
      steady to age 14; (ii) 'declining' class (15.1%) began with a significantly lower
      level of parental monitoring at age 11 and experienced a significant to through
      age 14. The declining class had increased significantly unadjusted (OR = 1.91;
      95% CI = 1.59, 2.23; P <= 0.001) and adjusted (aOR = 1.57; 95% CI = 1.24, 1.99; P
      = 0.01) odds of problem gambling compared with non-gambling. CONCLUSION: Low
      and/or declining parental monitoring of children between the ages of 11 and 14 is
      associated significantly with problem gambling when those children reach young
      adulthood.

PMID- 24321008
TI  - Inhibition of return affects contrast sensitivity.
AB  - Inhibition of return (IOR)-a slow response to targets at recently attended
      locations, is believed to play an important role in guiding behaviour. In the
      attention literature it has been shown that attentional capture by an exogenous
      cue affects contrast sensitivity so that it alters the appearance of low-contrast
      stimuli. Despite a significant amount of work over the last quarter century on
      IOR, it is not yet clear whether IOR operates in the same way. In the current
      study we examined the effect of IOR on contrast sensitivity-a very early, low
      level perceptual process. We found in both a detection task and an orientation
      discrimination task that lower contrast was needed to detect the stimulus
      (Experiment 1) and determine its orientation (Experiment 2) at the cued location
      than at the uncued location, at short cue-target delays, while higher contrast
      was needed at long delays-reflecting IOR. These results clearly demonstrate that
      IOR affects contrast sensitivity in a similar way as attentional capture does and
      suggest that IOR increases perceived contrast of an object in the uncued
      location.

PMID- 24321010
TI  - Measurement and analysis of adhesion property of lithium-ion battery electrodes
      with SAICAS.
AB  - The adhesion strength of lithium-ion battery (LIB) electrodes consisting of
      active material, a nanosized electric conductor, and a polymeric binder is
      measured with a new analysis tool, called the Surface and Interfacial Cutting
      Analysis System (SAICAS). Compared to the conventional peel test with the same
      electrode, SAICAS gives higher adhesion strength owing to its elaborate cutting
      based measurement system. In addition, the effects on the adhesion property of
      the polymeric binder type and content, electrode density, and measuring point are
      also investigated to determine whether SAICAS provides reliable results. The
      findings confirm SAICAS as an effective and promising tool to measure and analyze
      the adhesion properties of LIB electrodes. 

PMID- 24321009
TI  - Two new alkaloids from Portulaca oleracea and their cytotoxic activities.
AB  - Two new alkaloids named (3R)-3,5-bis(3-methoxy-4-hydroxyphenyl)-2,3-dihydro-2(1H)
      pyridinone (1) and 1,5-dimethyl-6-phenyl-1,2-dihydro-1,2,4-triazin-3(2H)-one (2),
      together with two known compounds (7'R)-N-feruloyl normetanephrine (3) and N
      trans-feruloyl tyramine (4) were isolated from the air-dried aerial parts of
      Portulaca oleracea L. Their structures and configurations were elucidated by
      spectroscopic methods including 1D NMR, 2D NMR, and HR-MS techniques. In
      addition, compounds 1-4 were tested for in vitro cytotoxic activities against
      human lung (K562 and A549) and breast (MCF-7 and MDA-MB-435) cancer cell lines.

PMID- 24321011
TI  - Theoretical and experimental study of inclusion complexes formed by isoniazid and
      modified beta-cyclodextrins: 1H NMR structural determination and antibacterial
      activity evaluation.
AB  - Me-beta-cyclodextrin (Me-betaCD) and HP-beta-cyclodextrin (HP-betaCD) inclusion
      complexes with isoniazid (INH) were prepared with the aim of modulating the
      physicochemical and biopharmaceutical properties of the guest molecule, a well
      known antibuberculosis drug. The architectures of the complexes were initially
      proposed according to NMR data Job plot and ROESY followed by density functional
      theory (DFT) calculations of (1)H NMR spectra using the PBE1PBE functional and 6
      31G(d,p) basis set, including the water solvent effect with the polarizable
      continuum model (PCM), for various inclusion modes, providing support for the
      experimental proposal. An analysis of the (1)H NMR chemical shift values for the
      isoniazid (H6',8' and H5',9') and cyclodextrins (H3,5) C(1)H hydrogens, which are
      known to be very adequately described by the DFT methodology, revealed them to be
      extremely useful, promptly confirming the inclusion complex formation. An
      included mode which describes Me-betaCD partially enclosing the hydrazide group
      of the INH is predicted as the most favorable supramolecular structure that can
      be used to explain the physicochemical properties of the encapsulated drug.
      Antibacterial activity was also evaluated, and the results indicated the
      inclusion complexes are a potential strategy for tuberculosis treatment. 

PMID- 24321012
TI  - Avocado/soybean unsaponifiables: a novel regulator of cutaneous wound healing,
      modelling and remodelling.
AB  - We investigated the effects of avocado/soybean unsaponifiables (ASU) on the
      healing response of cutaneous wound defect in rats. Sixty male rats were randomly
      divided into three groups including control, vehicle and treatment (n = 20 in
      each group). A 2 * 2 cm(2) wound defect was made on the dorsum. The control,
      vehicle and treatment groups were treated daily with topical application of
      saline, cream and cream/ASU for 10 days, respectively. The wounds were monitored
      daily. The animals were euthanised at 10, 20 and 30 days post injury (D). The dry
      matter, hydroxyproline, collagen, n-acetyl glucosamine (NAGLA) and n-acetyl
      galactosamine (NAGAA) contents of the skin samples were measured and the
      histopathological and biomechanical characteristics of the samples were
      investigated. Statistics of P < 0.05 was considered significant. Treatment
      significantly increased tissue glycosaminoglycans and collagen contents at
      various stages of wound healing compared to controls. Treatment modulated
      inflammation, improved fibroplasia and produced high amounts of scar tissue at
      short term. At long term, treatment reduced the scar tissue size and increased
      the quality and rate of wound contraction and reepithelisation compared to
      controls. The treated lesions were more cosmetically pleasing and had
      significantly higher biomechanical characteristics than controls. ASU was
      effective in rat wound healing. 

PMID- 24321013
TI  - Post-kala-azar dermal leishmaniasis mimicking leprosy relapse: a diagnostic
      dilemma.
AB  - OBJECTIVES: Post-kala-azar dermal leishmaniasis (PKDL) is well recognized in the
      Indian subcontinent and is not infrequently confused with leprosy. The present
      report describes findings in an unusual case of PKDL. METHODS: We report an adult
      male who presented with firm nodules on the face and extremities, along with
      hypopigmented macules on the neck with deformity and hypoesthesia over the right
      upper extremity. The patient had experienced similar lesions seven years
      previously and had used multibacillary multi-drug therapy for leprosy with
      complete resolution of the nodules. RESULTS: At the current presentation, skin
      smears from ear lobes and nodules were negative on Ziehl-Neelsen staining.
      Histopathological examination revealed a dermal lymphohistiocytic infiltrate with
      plasma cells. Giemsa staining of a tissue smear revealed Leishmania donovani
      bodies, and an rK39 antigen test was positive. The patient responded well to oral
      miltefosine. CONCLUSIONS: This case is noteworthy because the patient exhibited
      an unusual combination of healed leprosy sequelae and active PKDL lesions, which
      caused a diagnostic dilemma.

PMID- 24321014
TI  - Self-emulsifying drug delivery system and the applications in herbal drugs.
AB  - Herbal drugs have been used for thousands of years in the east and have had a
      recent resurgence in popularity among consumers in the west. However, most of
      herbal drug are poorly soluble and have hydrophobic properties and poor
      distribution, leading to reduced bioavailability and hence decreased treatment
      efficacy, requiring repeated administration or increased dose. In the past few
      decades, considerable attention has been focused on the development of self
      emulsifying drug delivery system (SEDDS) for herbal drugs. SEDDS is isotropic and
      thermodynamically stable solutions consisting of oil, surfactant, co-surfactant
      and drug that can spontaneously form oil-in-water micro/nanoemulsion when mixed
      with water under gentle stirring. The formulation can be a viable alternative to
      classical formulations to take advantage of their lipophilic nature and to solve
      their problems of poor solubility, poor bioavailability, low oral absorption and
      instability. The mechanism of self-emulsification, solubility studies,
      construction of phase diagram, optimization and characterization of herbal drugs
      loaded SEDDS formulation and in situ absorption evaluation of herbal drugs in rat
      intestine are presented in our article. 

PMID- 24321015
TI  - Use of fibrin monomer complex for screening for venous thromboembolism in the
      late pregnancy and post-partum period.
AB  - AIM: We measured fibrin monomer complex (FMC) levels in all subjects who gave
      birth at our hospital and evaluated the feasibility of using FMC for screening
      for venous thromboembolism (VTE) in patients during late pregnancy and the post
      partum period. METHODS: From August 2010 to January 2012, all women who gave
      birth at our hospital were included. FMC and D-dimer levels were determined
      during the late pregnancy and post-partum periods. Compression ultrasonography of
      the lower extremities was performed in women with high FMC values. RESULTS: Of
      the 673 women enrolled, measurements were performed in 595 women (88.4%) during
      late pregnancy and in 610 women (90.6%) during the post-partum period. The FMC
      levels were normal during late pregnancy in 400 women (67.2%) and during the post
      partum period in 399 women (78.5%) having vaginal delivery and 83 women (81.4%)
      who underwent a cesarean section. The FMC levels were abnormal during late
      pregnancy in 50 women (8.4%) and during the post-partum period in nine women
      (1.8%) having vaginal delivery and in none (0%) who underwent a cesarean section.
      Ultrasonography detected thrombi in three (6.0%) women during late pregnancy. The
      FMC levels were strongly correlated with D-dimer levels (R = 0.726, P < 0.0001,
      in late pregnancy; and R = 0.888, P < 0.0001, in the post-partum period following
      vaginal delivery). CONCLUSION: FMC levels could identify pregnancy-related
      abnormalities requiring compression ultrasonography examination, without changing
      the cut-off values for non-pregnant individuals. Thus, this marker may be used to
      screen for VTE.

PMID- 24321016
TI  - Phosphine-mediated regio- and stereoselective hydrocarboxylation of enynes.
AB  - A phosphine-mediated regio- and stereoselective addition reaction of diverse
      nucleophiles to yne-enones leading to polysubstituted 1,3-diene scaffolds in
      moderate to good yields has been reported. 

PMID- 24321017
TI  - Dielectrophoretic coassembly of binary colloidal mixtures in AC electric fields.
AB  - We report the novel use of dielectrophoresis (DEP) for fabricating a new class of
      composite structures composed of binary mixtures of micrometer-sized colloidal
      particles. Latex-latex and latex-yeast cells have been coassembled in a
      combinatorial manner into one- (1D) and two-dimensional (2D) architectures in
      spatially varying external alternating current (AC) electric fields using two
      different electrode geometries. The effects of voltage, frequency, particle size,
      particle concentration, and particle type are investigated in detail to determine
      how the relative polarizabilities of the particles can be tuned to influence the
      overall coassembly process. Our observations reveal key differences in the latex
      latex and latex-yeast cell assembly behavior especially in the case of 2D
      structure formation arising mainly due to the intrinsically high polarizability
      and polydispersity of the cells. This study is useful for making a potpourri of
      new hybrid structures with advanced functionalities for photonic and biosensing
      applications. 

PMID- 24321018
TI  - Fe-S cluster biogenesis in Gram-positive bacteria: SufU is a zinc-dependent
      sulfur transfer protein.
AB  - The biosynthesis of Fe-S clusters in Bacillus subtilis and other Gram-positive
      bacteria is catalyzed by the SufCDSUB system. The first step in this pathway
      involves the sulfur mobilization from the free amino acid cysteine to a sulfur
      acceptor protein SufU via a PLP-dependent cysteine desulfurase SufS. In this
      reaction scheme, the formation of an enzyme S-covalent intermediate is followed
      by the binding of SufU. This event leads to the second half of the reaction where
      a deprotonated thiol of SufU promotes the nucleophilic attack onto the persulfide
      intermediate of SufS. Kinetic analysis combined with spectroscopic methods
      identified that the presence of a zinc atom tightly bound to SufU (Ka = 10(17) M(
      1)) is crucial for its structural and catalytic competency. Fe-S cluster assembly
      experiments showed that despite the high degree of sequence and structural
      similarity to the ortholog enzyme IscU, the B. subtilis SufU does not act as a
      standard Fe-S cluster scaffold protein. The involvement of SufU as a dedicated
      agent of sulfur transfer, rather than as an assembly scaffold, in the biogenesis
      of Fe-S clusters in Gram-positive microbes indicates distinct strategies used by
      bacterial systems to assemble Fe-S clusters. 

PMID- 24321019
TI  - Long-term outcome at age 7-10 years after extreme prematurity - a prospective,
      two centre cohort study of children born before 25 completed weeks of gestation
      (1999-2003).
AB  - OBJECTIVE: We aimed to determine the long-term neurodevelopmental outcome in
      extremely preterm infants of 22-23 completed weeks' gestation as compared to
      infants of 24 weeks with immediate postnatal life support born in two German
      tertiary perinatal centres between 1999 and 2003. METHODS: Children were assessed
      for cognitive and neurological outcomes at the age of 7-10 years. The test
      battery included a neurological examination, the Wechsler Intelligence Scale for
      children (WISC-IV) and the Frostigs Developmental Test of Visual Perception (DTVP
      2). Gross motor function was classified according to the GMFCS and functional
      activity was assessed with the Lincoln Oseretzky Motor Development Scale (LOS KF
      18). RESULTS: Outcome data were available for 79/105 children. 75.9% of the
      entire study cohort showed no or mild impairment. There was no difference seen
      between the two gestational age groups. Risk factors for moderate or severe
      impairment were an intracerebral haemorrhage >II degrees  and/or periventricular
      leukomalacia or a retinopathy of prematurity >II degrees . Neither the
      gestational age (GA) nor the birth weight was associated with long-term outcome.
      CONCLUSIONS: Gestational age was not a predictor for long-term impairment of
      preterm infants born <25 completed weeks' GA. Other prognostic factors should be
      taken into account for counselling in the grey zone of viability.

PMID- 24321020
TI  - Antibody therapy for acute myeloid leukaemia.
AB  - Novel therapies with increased efficacy and decreased toxicity are desperately
      needed for the treatment of acute myeloid leukaemia (AML). The anti CD33
      immunoconjugate, gemtuzumab ozogamicin (GO), was withdrawn with concerns over
      induction mortality and lack of efficacy. However a number of recent trials
      suggest that, particularly in AML with favourable cytogenetics, GO may improve
      overall survival. This data and the development of alternative novel monoclonal
      antibodies (mAb) have renewed interest in the area. Leukaemic stem cells (LSC)
      are identified as the subset of AML blasts that reproduces the leukaemic
      phenotype upon transplantation into immunosuppressed mice. AML relapse may be
      caused by chemoresistant LSC and this has refocused interest on identifying and
      targeting antigens specific for LSC. Several mAb have been developed that target
      LSC effectively in xenogeneic models but only a few have begun clinical
      evaluation. Antibody engineering may improve the activity of potential new
      therapeutics for AML. The encouraging results seen with bispecific T cell
      engaging mAb-based molecules against CD19 in the treatment of B-cell acute
      lymphobalstic leukaemia, highlight the potential efficacy of engineered
      antibodies in the treatment of acute leukaemia. Potent engineered mAb, possibly
      targeting novel LSC antigens, offer hope for improving the current poor prognosis
      for AML. 

PMID- 24321021
TI  - Combination therapy of infliximab and thalidomide for refractory entero-Behcet's
      disease: a case report.
AB  - BACKGROUND: Behcet's disease (BD) is a systemic inflammatory disease with the
      histopathological features of leukocytoclastic vasculitis that affects nearly all
      organs and systems. When it involves the intestine, it is called entero-Behcet's
      disease (entero-BD). CASE PRESENTATION: Here we described a 23-year-old man with
      entero-BD refractory to conventional therapies who responded well to the
      combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-alpha
      antibody, and thalidomide. After combination treatment, the patient's symptoms
      improved greatly and his Crohn's Disease Activity Index (CDAI) score decreased
      from 344 to 52 points, accompanied by a body weight increase from 53 kg to 64 kg.
      A follow-up endoscopy performed 10 weeks after the treatment showed significant
      improvement and the patient's multiple ulcers had healed well. CONCLUSION: The
      combination therapy of infliximab and thalidomide appears to be clinically
      effective in a patient with refractory entero-BD. However, further studies need
      to be performed to evaluate the efficacy of this combination therapy.

PMID- 24321023
TI  - ED care: available, competent, affordable.

PMID- 24321022
TI  - A cross-sectional study assessing Australian general practice patients'
      intention, reasons and preferences for assistance with losing weight.
AB  - BACKGROUND: The high prevalence of overweight and obesity in the population is
      concerning, as these conditions increase an individual's risk of various chronic
      diseases. General practice is an ideal setting to target the reduction of
      overweight or obesity. Examining general practice patients' intentions to lose
      weight and preferences for assistance with managing their weight is likely to be
      useful in informing weight management care provided in this setting. Thus, this
      study aimed to: 1) identify the proportion and characteristics of patients
      intending to change weight in the next six months; 2) reasons for intending to
      change weight and preferences for different modes of weight management assistance
      in overweight and obese patients. METHODS: A cross-sectional study was conducted
      with 1,306 Australian adult general practice patients. Consenting patients
      reported via a touchscreen computer questionnaire their demographic
      characteristics, intention to lose weight in the next six months, reasons for
      wanting to lose weight, preferred personnel to assist with weight loss and
      willingness to accept support delivered via telephone, mobile and internet.
      RESULTS: Fifty six percent (n = 731) of patients intended to lose weight in the
      next six months. Females, younger patients, those with a level of education of
      trade certificate and above or those with high cholesterol had significantly
      higher odds of intending to lose weight. "Health" was the top reason for wanting
      to lose weight in normal weight (38%), overweight (57%) and obese (72%) patients.
      More than half of overweight (61%) or obese (74%) patients reported that they
      would like help to lose weight from one of the listed personnel, with the
      dietitian and general practitioner (GP) being the most frequently endorsed person
      to help patients with losing weight. Almost 90% of overweight or obese
      participants indicated being willing to accept support with managing their weight
      delivered via the telephone. CONCLUSIONS: Most overweight or obese general
      practice patients intended to lose their weight in the next six months for health
      reasons. Younger females, with higher level of education or had high cholesterol
      had significantly higher odds of reporting intending to lose weight in the next
      six months. An opportunity exists for GPs to engage patients in weight loss
      discussions in the context of improving health. Interventions involving GP and
      dietitians with weight management support delivered via telephone, should be
      explored in future studies in this setting.

PMID- 24321024
TI  - Flow volumes of internal jugular veins are significantly reduced in patients with
      cerebral venous sinus thrombosis.
AB  - The aim of this study was to investigate the flow volumes of the internal jugular
      veins (IJVs) in patients with cerebral venous sinus thrombosis (CVST) using
      Doppler ultrasonography (DUS) and to compare the findings with the control group.
      Forty patients diagnosed with CVST between 2008 and 2010 were included in the
      study. The patients diagnosed with a thrombosis via MRV and MRI underwent a
      bilateral examination of the IJVs by DUS. The patients were divided into three
      groups: Group I (n=29) unilateral total thrombosis; Group II (n= 6) bilateral
      diffuse thrombosis; and Group III (n=5) unilateral partial thrombosis. The IJV
      flow volumes of each group were compared to that of the control group (n=20). In
      Group I, the average flow volume was 53 ml/min on the side of the thrombosis. In
      Group II, the mean volume of the right and left IJV was 265 ml/min, and in Group
      III, the mean volume on the side of the partial thrombosis was 160 ml/min. The
      flow volume on the thrombosed side in Group I and Group III and the mean of the
      total bilateral flow volume in Group II were significantly lower than that of the
      control group. IJV flow volumes in the CVST group were significantly lower
      compared to the control group. Reduced flow volumes of the IJV may be diagnostic
      for CVST or an additional parameter to be considered with the use of MRI.

PMID- 24321025
TI  - Characterization of Lin-ve CD34 and CD117 cell population reveals an increased
      expression in bone marrow derived stem cells.
AB  - The purpose of the study was to evaluate the expression of CD45, CD34, Sca-1 and
      CD117 in mouse bone marrow, Lin-ve and Lin+ve population. Bone marrow cells were
      isolated from C57/BL6J mouse and mononuclear population was separated from rest
      of the cell population. With the help of Magnetic associated cell sorter (MACS),
      Linve and Lin+ve cells were separated from the bone marrow. The expression of
      CD45, CD34, Sca1 and CD117 was evaluated in bone marrow, Lin-ve and Lin+ve
      population by flow cytometry. We found a significant increase in the expression
      of CD34 and CD117 in Lin-ve as compared to the bone marrow and Lin+ve population.
      These findings suggest that Lin-ve population has higher expression of stem cell
      progenitor markers and could be useful for tissue repair and regeneration. 

PMID- 24321028
TI  - Reduced fetal growth in methadone-maintained pregnancies is not fully explained
      by smoking or socio-economic deprivation.
AB  - AIM: To determine if reduced fetal growth in infants of opioid-dependent mothers
      prescribed methadone maintenance in pregnancy is explained by cigarette smoking
      or socio-economic deprivation. DESIGN: Retrospective cohort study. SETTING: Inner
      city maternity unit in Scotland. PARTICIPANTS: A total of 366 singleton infants
      of methadone-prescribed opioid-dependent mothers compared with the Scottish birth
      population (n=103 366) as a whole. MEASUREMENTS: Primary outcome measures were
      birth weight and head circumference. FINDINGS: In infants of methadone-prescribed
      opioid-dependent mothers mean birth weight was 259 g [95% confidence interval
      (CI) 214-303 g; P<0.0001] less, and mean head circumference 1.01 cm (95% CI 0.87
      1.15 cm; P<0.0001) less than in controls, allowing for gestation, cigarette
      smoking, area deprivation, infant sex and maternal age and parity. This
      represents an adjusted difference of -0.61 (95% CI -0.52--0.71; P<0.0001) Z-score
      in mean birth weight and -0.77 (95% CI -0.66--0.89; P<0.0001) Z-score in mean
      head circumference. CONCLUSIONS: Reduced fetal growth in infants of opioid
      dependent mothers prescribed methadone maintenance in pregnancy is not fully
      explained by cigarette smoking, area deprivation, maternal age or parity.

PMID- 24321029
TI  - Spouses' reflections on implantable cardioverter defibrillator treatment with
      focus on the future and the end-of-life: a qualitative content analysis.
AB  - AIM: To explore future reflections of spouses living with an implantable
      cardioverter defibrillator recipient with focus on the end-of-life phase in an
      anticipated palliative phase. BACKGROUND: A history of or risk for life
      threatening arrhythmias may require an implantable cardioverter defibrillator.
      Despite the life-saving capacity of the device, eventually life will come to an
      end. As discussion about preferences of shock therapy at end-of-life phase seldom
      takes place in advance, the implantable cardioverter defibrillator recipients may
      face defibrillating shocks in the final weeks of their lives, adding to stress
      and anxiety in patients and their families. DESIGN: Qualitative study with in
      depth interviews analysed with a content analysis. METHODS: Interviews were
      performed with 18 spouses of medically stable implantable cardioverter
      defibrillator recipients during 2011-2012. RESULTS: The spouses described how
      they dealt with changes in life and an uncertain future following the implantable
      cardioverter defibrillator implantation. Six subcategories conceptualized the
      spouses' concerns: Aspiring for involvement; Managing an altered relationship;
      Being attentive to warning signs; Worries for deterioration in the partner's
      health; Waiting for the defibrillating shock; and Death is veiled in silence.
      CONCLUSION: Despite the partner's serious state of health; terminal illness or
      death and the role of the device was seldom discussed with healthcare
      professionals or the implantable cardioverter defibrillator recipient. Open and
      honest communication was requested as important to support coping with an
      unpredictable life situation and to reduce worries and uncertainty about the
      future and end-of-life.

PMID- 24321030
TI  - Abstracts of the 2nd Biennial Meeting of the Middle East Society for Sexual
      Medicine. Dubai, United Arab Emirates. October 31-November 2, 2013.

PMID- 24321031
TI  - Sensitivity of different assays for the serological diagnosis  of epidermolysis
      bullosa acquisita: analysis of a cohort of 24  Italian patients.
AB  - BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering
      disease characterized by tissue-bound and circulating autoantibodies to the
      dermal-epidermal junction. The autoantibody target is type VII collagen (Col VII)
      which is involved in dermal-epidermal adhesion. Diagnosis is made by clinical and
      histopathological findings, linear deposition of autoantibodies at the dermal
      epidermal junction detected by direct immunofluorescence, and binding to the
      dermal side of salt-split skin by indirect immunofluorescence (IIF). However, the
      detection of specific anti-Col VII reactivity has an important confirmatory
      value. METHODS: The humoral immune response in EBA sera was analysed by (i) IIF
      on human skin, (ii) a commercial Col VII ELISA, and (iii) immunoblotting on Col
      VII produced by an epithelial cell line. OBJECTIVE: The aim of this study was to
      compare the sensitivity of different approaches for the serological diagnosis of
      EBA. RESULTS: The vast majority of EBA sera (79.2%) bound to the Col VII non
      collagenous domains by a commercial ELISA, while a small proportion of patients
      (12.5%) exclusively reacted to the collagenous domain by immunoblotting. Of note,
      the autoantibodies reactivity to Col VII was more frequently detected by IB
      (91.7%) than by IIF (83.3%) and ELISA (79.2%). Interestingly, 2 out of 24 sera
      recognized Col VII epitopes undetectable in the native secreted protein but
      present in the context of extracellular matrix proteins, as assessed by
      immunomapping on Col VII-deficient skin. CONCLUSION: Our findings show that the
      use of multiple assays allows to improve diagnostic performance. An algorithm for
      efficient serological diagnosis of EBA is proposed.

PMID- 24321032
TI  - Task-switching cost and repetition priming: two overlooked confounds in the first
      set procedure of the Sternberg paradigm and how they affect memory set-size
      effects.
AB  - Subjects performed Sternberg-type memory recognition tasks (Sternberg paradigm)
      in four experiments. Category-instance names were used as learning and testing
      materials. Sternberg's original experiments demonstrated a linear relation
      between reaction time (RT) and memory-set size (MSS). A few later studies found
      no relation, and other studies found a nonlinear relation (logarithmic) between
      the two variables. These deviations were used as evidence undermining Sternberg's
      serial scan theory. This study identified two confounding variables in the fixed
      set procedure of the paradigm (where multiple probes are presented at test for a
      learned memory set) that could generate a MSS RT function that was either flat or
      logarithmic rather than linearly increasing. These two confounding variables were
      task-switching cost and repetition priming. The former factor worked against
      smaller memory sets and in favour of larger sets whereas the latter factor worked
      in the opposite way. Results demonstrated that a null or a logarithmic RT-to-MSS
      relation could be the artefact of the combined effects of these two variables.
      The Sternberg paradigm has been used widely in memory research, and a thorough
      understanding of the subtle methodological pitfalls is crucial. It is suggested
      that a varied-set procedure (where only one probe is presented at test for a
      learned memory set) is a more contamination-free procedure for measuring the MSS
      effects, and that if a fixed-set procedure is used, it is worthwhile examining
      the RT function of the very first trials across the MSSs, which are presumably
      relatively free of contamination by the subsequent trials.

PMID- 24321033
TI  - Silences and moral narratives: infanticide as reproductive disruption.
AB  - Infanticide is a widespread practice, yet few ethnographic and theoretical works
      examine this. Drawing on ethnographic research conducted in the Indian Himalayas,
      I argue that infanticide is a form of reproductive disruption that elicits both
      public moral judgments and private silences. In this Himalayan context, the
      stigmas of abortion and premarital sex prevent community acknowledgement of
      infanticide and baby abandonment. Unmarried women hide their pregnancies, deliver
      and abandon their babies, and later are rushed to the hospital with postdelivery
      complications. While biomedical doctors deal with the debris of infanticide
      (postpartum hemorrhage), there is no formal accounting of the practice. I argue
      that by regarding infanticide as a form of reproductive disruption, we can open
      up women's narratives of pain and suffering that are silenced because of moral
      repugnance. 

PMID- 24321035
TI  - Enhanced membrane protein expression by engineering increased intracellular
      membrane production.
AB  - BACKGROUND: Membrane protein research is frequently hampered by the low natural
      abundance of these proteins in cells and typically relies on recombinant gene
      expression. Different expression systems, like mammalian cells, insect cells,
      bacteria and yeast are being used, but very few research efforts have been
      directed towards specific host cell customization for enhanced expression of
      membrane proteins. Here we show that by increasing the intracellular membrane
      production by interfering with a key enzymatic step of lipid synthesis, enhanced
      expression of membrane proteins in yeast is achieved. RESULTS: We engineered the
      oleotrophic yeast, Yarrowia lipolytica, by deleting the phosphatidic acid
      phosphatase, PAH1, which led to massive proliferation of endoplasmic reticulum
      (ER) membranes. For all eight tested representatives of different integral
      membrane protein families, we obtained enhanced protein accumulation levels and
      in some cases enhanced proteolytic integrity in the ?pah1 strain. We analysed the
      adenosine A2AR G-protein coupled receptor case in more detail and found that
      concomitant induction of the unfolded protein response in the ?pah1 strain
      enhanced the specific ligand binding activity of the receptor. These data
      indicate an improved quality control mechanism for membrane proteins accumulating
      in yeast cells with proliferated ER. CONCLUSIONS: We conclude that redirecting
      the metabolic flux of fatty acids away from triacylglycerol- and sterylester
      storage towards membrane phospholipid synthesis by PAH1 gene inactivation,
      provides a valuable approach to enhance eukaryotic membrane protein production.
      Complementary to this improvement in membrane protein quantity, UPR co-induction
      further enhances the quality of the membrane protein in terms of its proper
      folding and biological activity. Importantly, since these pathways are conserved
      in all eukaryotes, it will be of interest to investigate similar engineering
      approaches in other cell types of biotechnological interest, such as insect cells
      and mammalian cells.

PMID- 24321034
TI  - Contributions of major smoking-related diseases to reduction in life expectancy
      associated with smoking in Chinese adults: a cross-sectional study.
AB  - BACKGROUND: Cigarette smoking is a prominent risk factor for a wide range of
      diseases. The current study aimed to evaluate the impact of smoking on deaths
      from major smoking-related diseases (neoplasms, vascular diseases and respiratory
      diseases) in Chinese adults by estimating the potential gains in life expectancy
      (LE) that would accrue from eliminating deaths from these diseases, and to
      determine the contribution of each disease to the reduction in LE associated with
      smoking. METHODS: Two cohorts of Chinese smokers and non-smokers were constructed
      from a retrospective national mortality survey that had been conducted in 1989
      1991 and included one million all-cause deaths among adults during 1986-1988 in
      103 geographical regions. For each cohort, potential gains in LE by eliminating
      deaths from each major smoking-related disease were estimated. The contributions
      of each disease to smoking-associated reduction in LE were assessed using the LE
      decomposition approach. RESULTS: Among the major smoking-related diseases, it was
      estimated that elimination of vascular diseases would provide the greatest
      potential gain in LE (years), regardless of smoking status. The gains for smokers
      versus non-smokers in populations of urban men, urban women, rural men and rural
      women aged 35 years were 3.5 vs. 4.3, 3.8 vs. 4.1, 2.4 vs. 3.0, and 2.6 vs. 2.9
      years, respectively. Respiratory diseases contributed most to smoking-associated
      LE reductions in urban women, rural men and rural women of 43.6%, 46.4%, and
      62.9%, respectively. In urban men, neoplasms contributed most to smoking
      associated LE reduction, their contribution being estimated as 45.8%.
      CONCLUSIONS: Respiratory disease has the greatest influence on the LE reduction
      associated with smoking. Thus, smoking prevention could significantly reduce
      deaths from respiratory disease and improve LE.

PMID- 24321036
TI  - Omentin serum levels and omentin gene Val109Asp polymorphism in patients with
      psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disease of uncertain
      pathogenesis. Omentin is a new adipokine with anti-inflammatory properties;
      however, the relationship between psoriasis and omentin has not been fully
      established yet. OBJECTIVES: This study was designed to evaluate the relationship
      between psoriasis and omentin serum levels and Val109Asp polymorphism in exon 4
      of the omentin gene. METHODS: Forty-nine patients with plaque-type psoriasis and
      39 healthy subjects were included in the study. Omentin concentrations were
      determined by using enzyme-linked immunosorbent assay. Val109Asp polymorphism in
      exon 4 of the omentin gene was assessed by the polymerase chain reaction
      restriction fragment length polymorphism method. Genotypes were determined
      according to the bands formed in agarose electrophoresis gels. In the statistical
      analysis, the level of significance was set at P < 0.05. RESULTS: The serum
      omentin levels of the patients with psoriasis (354.2 +/- 152.0) were found to be
      significantly lower than those in the control group (488.7 +/- 190.3) (P =
      0.001). A moderate level negative correlation was determined between serum
      omentin level and body mass index and waist circumference. No significant
      differences were observed between the patient and control groups in terms of the
      genotype and allele frequency of Val109Asp polymorphism in exon 4 of the omentin
      gene (P > 0.05). CONCLUSIONS: Omentin serum levels were determined to be low in
      patients with psoriasis. No significant difference was found regarding Val109Asp
      polymorphism of the omentin gene. To the best of our knowledge, our study is the
      first clinical study to examine the relationship between psoriasis and omentin in
      terms of serum and genomic levels.

PMID- 24321037
TI  - FCS study of the structural stability of lysozyme in the presence of morpholinium
      salts.
AB  - Ability of the ionic liquids to alter the structural stability of proteins in
      aqueous solution is a topic of considerable interest in modern bioscientific
      research because of possible applications of these substances in protein
      purification and as refolding agents. A few early studies involving the
      imidazolium ionic liquids have demonstrated their role as both denaturants and
      refolding agents. As the influence of an ionic liquid on a given protein depends
      on the identity of both species, it is necessary to extend the studies to a wider
      number of ionic liquids and proteins to obtain insight into the mechanism of
      interaction between the two and to arrive at a comprehensive picture. It is in
      this context that we have studied the effect of two morpholinium salts,
      [Mor1,2][Br] and [Mor1,4][Br], differing in the alkyl chain length of cation, on
      chicken egg white lysozyme in its native and chemically denatured states
      employing primarily the fluorescence correlation spectroscopy (FCS) technique.
      Fluorescence signal of Alexa488-labeled lysozyme (A488-Lysz) has been used to
      determine the changes in hydrodynamic radius of protein in the presence of
      additives. The results reveal a conformational dynamics of lysozyme with a time
      constant of 56 +/- 10 MUs in its native state. It is observed, when in its native
      state, both the morpholinium salts induce structural changes of lysozyme.
      However, when in its unfolded state, [Mor1,4][Br] at low concentration compacts
      the protein, but at higher concentration, it stabilizes the unfolded state,
      unlike [Mor1,2][Br], which compacts lysozyme at both low and high concentrations.
      A comparison of the effect of these salts and arginine, a protein stabilizer, on
      lysozyme indicates that [Mor1,2][Br] is a superior compacting agent for the
      unfolded state of the protein compared to arginine. 

PMID- 24321038
TI  - Menstrual and fertility outcomes following the surgical management of postpartum
      haemorrhage: a systematic review.
AB  - BACKGROUND: Uterine-sparing surgical interventions have long been practiced as an
      alternative to hysterectomy in the management of severe postpartum haemorrhage
      (PPH); however, the risks of impairment of subsequent fertility from such
      procedures are unclear. OBJECTIVE: To evaluate the menstrual and fertility
      outcomes following radiological or conservative surgical interventions for severe
      PPH. SEARCH STRATEGY: A systematic review of English and non-English articles
      using the Cochrane Library 2012, PubMed (1950-2012), Embase (1980-2012), and the
      National Research Register. The keywords used for our search included
      'fertility', 'reproductive outcome', 'postpartum haemorrhage', 'embolisation',
      'hypogastric artery ligation', 'B-Lynch suture', 'stepwise uterine
      devascularisation', 'tamponade', and 'uterine compression sutures'. SELECTION
      CRITERIA: Studies including human female subjects with at least five cases. DATA
      COLLECTION AND ANALYSIS: Independent extraction of articles by two authors using
      predefined data fields, including study quality indicators. MAIN RESULTS: We
      identified 402 publications and after exclusions, 28 studies were included in the
      systematic review. Seventeen studies (675 women) reported on the fertility
      outcomes after uterine artery embolisation, five studies (195 women) reported on
      the fertility outcomes after uterine devascularisation, and six studies (125
      women) reported on the fertility outcomes following uterine compression sutures.
      Overall, 553 out of 606 (91.25%) women resumed menstruation within 6 months of
      delivery. One hundred and eighty-three out of 235 (77.87%) women who desired
      another pregnancy achieved conception. AUTHOR'S CONCLUSIONS: Uterine-sparing
      radiological and surgical techniques for the management of severe PPH do not
      appear to adversely affect the menstrual and fertility outcomes in most women;
      however, the number of studies and the quality of the available evidence is of
      concern.

PMID- 24321040
TI  - Investigation of the interactions involved in the formation of nanotubes from
      organogelators.
AB  - Investigations into the formation of nanosized structures, particularly
      nanotubes, by a diamide ester compound are reported. Two aspects are concurrently
      examined: the role of the solvent and the role of the alkyl chain. The former is
      addressed by using a benzene derivative (o-xylene) and a totally saturated double
      ring (trans-decahydronaphthalene) whereas the latter is achieved by replacing the
      hydrogenous alkyl chain with its fluorinated counterpart while keeping the
      overall architecture the same. The thermodynamic behavior by differential
      scanning calorimetry, the morphology by transmission electron microscopy, and the
      structure by X-ray scattering and small-angle neutron scattering are studied.
      Despite the identical architecture, the fluorinated molecule does not produce any
      nanotubes, unlike its totally hydrogenous counterpart. Also, o-xylene prevents
      the hydrogenous molecule from forming nanotubes, while nanotapes are produced
      instead. Conversely, the fluorinated molecule produces regularly twisted
      protostructures in either solvent. Neutron scattering experiments show that the
      fluorinated alky chain is located within the core of this structure. This
      suggests that the prerequisite for forming nanotubes relies on the necessity of
      the alkyl group to point outward. 

PMID- 24321039
TI  - Effect of cytochrome P-450 epoxygenase and hydroxylase metabolites on rat
      myometrium contractility in non-pregnancy, late pregnancy and late pregnancy
      under inflammatory conditions.
AB  - AIM: The aim of the present experimental study was to assess the tocolytic effect
      of eicosanoids on myometrium from non-pregnant and pregnant rats with or without
      an induced inflammatory condition. METHODS: Three hundred myometrial rings were
      obtained by median laparotomy from 50 Sprague-Dawley rats divided into three
      groups: (i) non-pregnant (n = 15); (ii) pregnant in absence (n = 20); or (iii)
      pregnant in presence (n = 15) of lipopolysaccharide treatment, timed at 22 days
      of pregnancy. Spontaneous contractile activities were compared by isometric
      tension measurements. The effects of epoxy- and hydroxyeicosanoids derived from
      arachidonic acid as well as specific enzyme inhibitors were assessed. Changes
      were expressed as percentage of basal activity by calculating the area under the
      curve as a function of drug concentration and compared to the effect of the
      vehicle. RESULTS: A decrease in contractile activity ranging 10-25% was observed
      upon addition of epoxy- and hydroxyeicosanoids. Increasing epoxyeicosanoid
      bioavailability by inhibiting their degradation induced a tocolytic effect in the
      non-pregnant group (20%) and in inflammation-induced condition (40%). There was a
      significant difference in reactivity between groups and pregnancy condition.
      Semiquantification of metabolic enzymes that produce (cytochrome P-450
      epoxygenase) and degrade (soluble epoxide hydrolase) epoxyeicosanoids by western
      blot analysis revealed that these enzymes were mainly detected in the non
      pregnant group. CONCLUSION: Eicosanoids can modify myometrial reactivity and
      their presence and effects are amplified in non-pregnant and in inflammation
      induced condition. Our data suggest that in contrast to prostaglandins,
      epoxyeicosatrienoic acids are likely involved in the quiescence phase of
      parturition because they reduce the rhythmic contractile activity of uterine
      tissues in pregnant rats.

PMID- 24321041
TI  - Fetal death and reduced birth rates associated with exposure to lead-contaminated
      drinking water.
AB  - This ecologic study notes that fetal death rates (FDR) during the Washington DC
      drinking water "lead crisis" (2000-2004) peaked in 2001 when water lead levels
      (WLLs) were highest, and were minimized in 2004 after public health interventions
      were implemented to protect pregnant women. Changes in the DC FDR vs neighboring
      Baltimore City were correlated to DC WLL (R(2) = 0.72). Birth rates in DC also
      increased versus Baltimore City and versus the United States in 2004-2006, when
      consumers were protected from high WLLs. The increased births in DC neighborhoods
      comparing 2004 versus 2001 was correlated to the incidence of lead pipes (R(2) =
      0.60). DC birth rates from 1999 to 2007 correlated with proxies for maternal
      blood lead including the geometric mean blood lead in DC children (R(2) = 0.68)
      and the incidence of lead poisoning in children under age 1.3 years (R(2) =
      0.64). After public health protections were removed in 2006, DC FDR spiked in
      2007-2009 versus 2004-2006 (p < 0.05), in a manner consistent with high WLL
      health risks to consumers arising from partial lead service line replacements,
      and DC FDR dropped to historically low levels in 2010-2011 after consumers were
      protected and the PSLR program was terminated. Re-evaluation of a historic
      construction-related miscarriage cluster in the USA Today Building (1987-1988),
      demonstrates that high WLLs from disturbed plumbing were a possible cause.
      Overall results are consistent with prior research linking increased lead
      exposure to higher incidence of miscarriages and fetal death, even at blood lead
      elevations (~5 MUg/dL) once considered relatively low. 

PMID- 24321042
TI  - Specific recognition of reproductive parasite workers by nest-entrance guards in
      the bumble bee Bombus terrestris.
AB  - BACKGROUND: The impact of social parasites on their hosts' fitness is a strong
      selective pressure that can lead to the evolution of adapted defence strategies.
      Guarding the nest to prevent the intrusion of parasites is a widespread response
      of host species. If absolute rejection of strangers provides the best protection
      against parasites, more fine-tuned strategies can prove more adaptive. Guarding
      is indeed costly and not all strangers constitute a real threat. That is
      particularly true for worker reproductive parasitism in social insects since only
      a fraction of non-nestmate visitors, the fertile ones, can readily engage in
      parasitic reproduction. Guards should thus be more restrictive towards fertile
      than sterile non-nestmate workers. We here tested this hypothesis by examining
      the reaction of nest-entrance guards towards nestmate and non-nestmate workers
      with varying fertility levels in the bumble bee Bombus terrestris. Because social
      recognition in social insects mainly relies on cuticular lipids (CLs), chemical
      analysis was also conducted to examine whether workers' CLs could convey the
      relevant information upon which guards could base their decision. We thus aimed
      to determine whether an adapted defensive strategy to worker reproductive
      parasitism has evolved in B. terrestris colonies. RESULTS: Chemical analysis
      revealed that the cuticular chemical profiles of workers encode information about
      both their colony membership and their current fertility, therefore providing
      potential recognition cues for a suitable adjustment of the guards' defensive
      decisions. We found that guards were similarly tolerant towards sterile non
      nestmate workers than towards nestmate workers. However, as predicted, guards
      responded more aggressively towards fertile non-nestmates. CONCLUSION: Our
      results show that B. terrestris guards discriminate non-nestmates that differ in
      their reproductive potential and respond more strongly to the individuals that
      are a greatest threat for the colony. Cuticular hydrocarbons are the probable
      cues underlying the specific recognition of reproductive parasites, with the
      specific profile of highly fertile bees eliciting the agonistic response when
      combined with non-colony membership information. Our study therefore provides a
      first piece of empirical evidence supporting the hypothesis that an adapted
      defensive strategy against worker reproductive parasitism exists in B. terrestris
      colonies.

PMID- 24321044
TI  - Utility of multimaterial 3D printers in creating models with pathological
      entities to enhance the training experience of neurosurgeons.
AB  - The advent of multimaterial 3D printers allows the creation of neurosurgical
      models of a more realistic nature, mimicking real tissues. The authors used the
      latest generation of 3D printer to create a model, with an inbuilt pathological
      entity, of varying consistency and density. Using this model the authors were
      able to take trainees through the basic steps, from navigation and planning of
      skin flap to performing initial steps in a craniotomy and simple tumor excision.
      As the technology advances, models of this nature may be able to supplement the
      training of neurosurgeons in a simulated operating theater environment, thus
      improving the training experience. 

PMID- 24321043
TI  - Tax posttranslational modifications and interaction with calreticulin in MT-2
      cells and human peripheral blood mononuclear cells of human T cell lymphotropic
      virus type-I-associated myelopathy/tropical spastic paraparesis patients.
AB  - The human retrovirus human T cell lymphotropic virus type-I (HTLV-1) is the
      etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP). Axonal degeneration in HAM/TSP patients occurs without neuron
      infection, with the secreted viral Tax protein proposed to be involved. We
      previously found that Tax secreted into the culture medium of MT-2 cells (HTLV-1
      infected cell line) produced neurite retraction in neuroblastoma cells
      differentiated to neuronal type. To assess the relevance of Tax posttranslational
      modifications on this effect, we addressed the question of whether Tax secreted
      by MT-2 cells and peripheral blood mononuclear cells (PBMCs) of HTLV-1-infected
      subjects is modified. The interaction of Tax with calreticulin (CRT) that
      modulates intracellular Tax localization and secretion has been described. We
      studied Tax localization and modifications in MT-2 cells and its interaction with
      CRT. Intracellular Tax in MT-2 cells was assessed by flow cytometry,
      corresponding mainly to a 71-kDa protein followed by western blot. This protein
      reported as a chimera with gp21 viral protein-confirmed by mass spectrometry
      showed no ubiquitination or SUMOylation. The Tax-CRT interaction was determined
      by confocal microscopy and coimmunoprecipitation. Extracellular Tax from HAM/TSP
      PBMCs is ubiquitinated according to western blot, and its interaction with CRT
      was shown by coimmunoprecipitation. A positive correlation between Tax and CRT
      secretion was observed in HAM/TSP PBMCs and asymptomatic carriers. For both
      proteins inhibitors and activators of secretion showed secretion through the
      endoplasmic reticulum-Golgi complex. Tax, present in PBMC culture medium,
      produced neurite retraction in differentiated neuroblastoma cells. These results
      suggest that Tax, whether ubiquitinated or not, is active for neurite retraction.

PMID- 24321045
TI  - In situ control of local pH using a boron doped diamond ring disk electrode:
      optimizing heavy metal (mercury) detection.
AB  - A novel electrochemical approach to modifying aqueous solution pH in the vicinity
      of a detector electrode in order to optimize the electrochemical measurement
      signal is described. A ring disk electrode was employed where electrochemical
      decomposition of water on the ring was used to generate a flux of protons which
      adjusts the local pH controllably and quantifiably at the disk. Boron doped
      diamond (BDD) functioned as the electrode material given the stability of this
      electrode surface especially when applying high potentials (to electrolyze water)
      for significant periods of time. A pH sensitive iridium oxide electrode
      electrodeposited on the disk electrode demonstrated that applied positive
      currents on the BDD ring, up to +50 MUA, resulted in a local pH decrease of over
      4 orders of magnitude, which remained stable over the measurement time of 600 s.
      pH generation experiments were found to be in close agreement with finite element
      simulations. The dual electrode arrangement was used to significantly improve the
      stripping peak signature for Hg in close to neutral conditions by the generation
      of pH = 2.0, locally. With the ability to create a localized pH change
      electrochemically in the vicinity of the detector electrode, this system could
      provide a simple method for optimized analysis at the source, e.g., river and sea
      waters. 

PMID- 24321046
TI  - Effect of genotype on duodenal expression of nutrient transporter genes in dairy
      cows.
AB  - BACKGROUND: Studies have shown clear differences between dairy breeds in their
      feed intake and production efficiencies. The duodenum is critical in the
      coordination of digestion and absorption of nutrients. This study examined gene
      transcript abundance of important classes of nutrient transporters in the
      duodenum of non lactating dairy cows of different feed efficiency potential,
      namely Holstein-Friesian (HF), Jersey (JE) and their F1 hybrid. Duodenal
      epithelial tissue was collected at slaughter and stored at -80 degrees C. Total
      RNA was extracted from tissue and reverse transcribed to generate cDNA. Gene
      expression of the following transporters, namely nucleoside; amino acid; sugar;
      mineral; and lipid transporters was measured using quantitative real-time RT-PCR.
      Data were statistically analysed using mixed models ANOVA in SAS. Orthogonal
      contrasts were used to test for potential heterotic effects and spearman
      correlation coefficients calculated to determine potential associations amongst
      gene expression values and production efficiency variables. RESULTS: While there
      were no direct effects of genotype on expression values for any of the genes
      examined, there was evidence for a heterotic effect (P < 0.05) on ABCG8, in the
      form of increased expression in the F1 genotype compared to either of the two
      parent breeds. Additionally, a tendency for increased expression of the amino
      acid transporters, SLC3A1 (P = 0.072), SLC3A2 (P = 0.081) and SLC6A14 (P = 0.072)
      was also evident in the F1 genotype. A negative (P < 0.05) association was
      identified between the expression of the glucose transporter gene SLC5A1 and
      total lactational milk solids yield, corrected for body weight. Positive
      correlations (P < 0.05) were also observed between the expression values of genes
      involved in common transporter roles. CONCLUSION: This study suggests that
      differences in the expression of sterol and amino acid transporters in the
      duodenum could contribute towards the documented differences in feed efficiency
      between HF, JE and their F1 hybrid. Furthermore, positive associations between
      the expression of genes involved in common transporter roles suggest that these
      may be co-regulated. The study identifies potential candidates for investigation
      of genetic variants regulating nutrient transport and absorption in the duodenum
      in dairy cows, which may be incorporated into future breeding programmes.

PMID- 24321048
TI  - Corrigendum.

PMID- 24321047
TI  - IgG4 related disease - a retrospective descriptive study highlighting Canadian
      experiences in diagnosis and management.
AB  - BACKGROUND: Appreciating the utility of published diagnostic criteria for
      autoimmune pancreatitis, when compared to the characteristics of patients
      clinically managed as having disease, informs and refines ongoing clinical
      practice. METHODS: Comparative retrospective descriptive evaluation of patients
      with autoimmune pancreatitis including dedicated radiology review. RESULTS: 66
      subjects with radiographic OR clinical features of autoimmune pancreatitis were
      initially identifiable (Male: n = 50), with 55 confirmed for evaluation. The most
      common presentation included pain (67%), weight loss (65%), and jaundice (62%).
      Diffuse enlargement of the pancreas was evident in 38%, whilst multifocal, focal,
      or atrophic changes were seen in 7%, 33% and 9% respectively. 13% had no
      pancreatic parenchymal involvement. Peripheral rim enhancement was seen in 23
      patients (42%). Where discernible, disease was a) Sclerosing pancreatitis and
      cholangitis, n = 21; b) Sclerosing cholangitis, n = 9; c) Sclerosing
      pancreatitis, n = 4; d) Sclerosing pancreatitis and cholangitis with pancreatic
      pseudotumour, n = 7; e) Sclerosing cholangitis with hepatic pseudotumour, n = 3;
      f) Sclerosing pancreatitis with pancreatic pseudotumour, n = 1. 56% of the
      patients had systemic manifestations and the median serum IgG4 at diagnosis was
      5.12 g/L. The Korean criteria identified most patients (82%) compared to HISORt
      (55%) or the Japan Pancreas Society (56%). The majority (HISORt 60%; Japan
      Pancreas Society 55%; Korean 58%) met diagnostic criterion by radiological
      findings and elevated serum IgG4. Treatment and response did not differ when
      stratified by diagnostic criteria. CONCLUSION: Our descriptive and retrospective
      dataset confirms that in non-expert practice settings, autoimmune pancreatitis
      scoring systems with a focus on radiology and serology capture most patients who
      are clinically felt to have disease.

PMID- 24321049
TI  - A practical method for preparation of pneumococcal and nontypeable Haemophilus
      influenzae inocula that preserves viability and immunostimulatory activity.
AB  - BACKGROUND: Convenience is a major reason for using killed preparations of
      bacteria to investigate host-pathogen interactions, however, host responses to
      such preparations can result in different outcomes when compared to live
      bacterial stimulation. We investigated whether cryopreservation of Streptococcus
      pneumoniae and nontypeable Haemophilus influenzae (NTHi) permitted investigation
      of host responses to infection without the complications of working with freshly
      prepared live bacteria on the day of experimental challenge. FINDINGS: S.
      pneumoniae and NTHi retained >90% viability following cryopreservation in fetal
      calf serum for at least 8 weeks. Host responses to live, cryopreserved (1 week
      and 4 weeks), heat-killed or ethanol-killed S. pneumoniae and NTHi were assessed
      by measuring cytokine release from stimulated peripheral blood mononuclear cells
      (PBMCs). We found that cryopreserved bacteria, in contrast to heat-killed and
      ethanol-killed preparations, resulted in comparable levels of inflammatory
      cytokine release from PBMCs when compared with fresh live bacterial cultures.
      CONCLUSION: Cryopreservation of S. pneumoniae and NTHi does not alter the
      immunostimulatory properties of these species thereby enabling reproducible and
      biologically relevant analysis of host responses to infection. This method also
      facilitates the analysis of multiple strains on the same day and allows
      predetermination of culture purity and challenge dose.

PMID- 24321050
TI  - High hopes for CB(2) receptors in neurogenesis.
AB  - During life, new neurons are continually added to hippocampal circuitry, with
      evidence suggesting that these adult-born neurons are functionally linked to
      cognition and emotion. The mammalian brain contains actively dividing neural stem
      cells in discrete regions, including the subventricular zone of the lateral
      ventricles and the subgranular zone of the dentate gyrus. Once mature, these
      neurons integrate into neuronal networks, forming synaptic connections with
      interneurons, mossy cells and CA3 pyramidal cells LINKED ARTICLE: This article is
      a commentary on Avraham et al., pp. 468-479 of volume 171 issue 2. To view this
      paper visit http://dx.doi.org/10.1111/bph.12478.

PMID- 24321051
TI  - Adolescent predictors and environmental correlates of young adult alcohol use
      problems.
AB  - AIMS: To examine the rates of young adult alcohol and drug use and alcohol
      problems, adolescent predictors of young adult alcohol problems and correlations
      with young adult social, work and recreational environments. DESIGN: Adolescents
      were followed longitudinally into young adulthood. Predictors were measured in
      grade 9 (average age 15), and environmental correlates and outcomes in young
      adulthood (average age 21). SETTING: Students recruited in Victoria, Australia in
      2002, were resurveyed in 2010/11. PARTICIPANTS: Analytical n=2309, 80% retention.
      MEASUREMENTS: Adolescent self-report predictors included past-month alcohol use.
      Young adults completed the Alcohol Use Disorders Identification Test (AUDIT)
      together with reports of environmental influences. FINDINGS: Comparisons to
      United States national school graduate samples revealed higher rates of alcohol,
      tobacco and illicit drug use (other than cannabis) in Victoria. For example,
      rates of past month use at age 21-22 were: alcohol 69.3% US versus 84.9%, 95%
      confidence interval (CI) 81.3-88.6% Victoria; illicit drugs (other than cannabis)
      8.8 versus 12.7%, CI 9.7-15.7%. AUDIT alcohol problems (scored 8+) were
      identified for 41.2%, CI 38.8-43.6% of young adults in Victoria. The likelihood
      of young adult alcohol problems was higher for frequent adolescent alcohol users
      and those exposed to environments characterized by high alcohol use and problems
      in young adulthood. CONCLUSIONS: High rates of alcohol problems are evident in
      more than two in five Australian young adults, and these problems appear to be
      influenced both by earlier patterns of adolescent alcohol use and by young adult
      social, work and recreational environments.

PMID- 24321052
TI  - Novel polymorphisms in the promoter region of the perforin gene among distinct
      Brazilian populations and their functional impact.
AB  - Cytotoxic T lymphocytes and natural killer cells play a crucial role in
      eliminating tumour and virus-infected cells. The perforin is a key part of the
      arsenal that these cells use to destroy their targets. In this study, we
      characterized single-nucleotide polymorphisms (SNPs) located in the promoter
      region of the perforin gene among distinct Brazilian ethnic groups. The study was
      carried out by sequencing this region in three groups: European, African and
      Asian descents. We demonstrated for the first time the occurrence of three new
      polymorphisms in the promoter region of gene PRF1: 494A/G (rs78058707), 720G/A
      (rs75925789) and 1176C/T (rs75183511). Three other SNPs already described in the
      literature 63A/G (rs35401316), 112A/G (rs10999428) and 1012C/T (rs35069510) were
      also detected. The SNPs are distributed differently in the ethnic groups studied.
      The 112G allele was observed at high frequency, especially among Asian descents
      (48.1%). The 1012T allele was detected only among European descents, the 494G
      allele only among Asian descents and 1176T allele only in African descents. Based
      on the association between the polymorphisms described, ten new haplotypes were
      originated. In functional analysis, we noticed that SNPs present in most common
      haplotypes cannot induce significant differences in expression levels of perforin
      alone. In conclusion, this study demonstrates for the first time the existence of
      three new polymorphisms in perforin promoter and, contrary to what was stated,
      the presence of these SNPs does not alter the levels of protein expression. 

PMID- 24321053
TI  - Multiple eruptive dermatofibromas related to imatinib treatment.

PMID- 24321054
TI  - Determinants and protective behaviours regarding tick bites among school children
      in the Netherlands: a cross-sectional study.
AB  - BACKGROUND: Lyme borreliosis (LB) is the most common tick-borne disease in the
      United States and Europe. The incidence is 13.4 per 100,000 inhabitants in the
      United States and more than 300 per 100,000 inhabitants in Europe. Children are
      at highest risk of LB. In the Netherlands in 2007, the incidence of tick bites in
      children between 10-14 years varied from 7,000 -11,000 per 100,000, depending on
      age. This study among Dutch school children aimed to examine the knowledge,
      perceived threat, and perceived importance of protective behaviour in relation to
      tick bites and their potential consequences. METHODS: In April 2012, the
      municipal health services (MHS) contacted primary schools to recruit children 9
      13 years by telephone, e-mail, or advertisement in MHS newsletters. In total,
      1,447 children from 40 schools participated in this study by completing a
      specifically developed and pretested compact paper questionnaire. Regression
      models were used to determine which covariates (e.g. forest cover, previous
      education, knowledge) are associated with our response variables. RESULTS: 70% (n
      = 1,015) of the children answered at least six out of seven knowledge questions
      correctly. The vast majority (93%; n = 1345) regarded body checks as very or
      somewhat important, 18% (n = 260) was routinely checked by their parents. More
      frequent body checks were associated with good knowledge about ticks and tick
      borne diseases and knowing persons who got ill after tick bite. Children in areas
      with a higher forest cover were more likely to be checked frequently.
      CONCLUSIONS: Most children have a good knowledge of ticks and the potential
      consequences of tick bites. Knowing persons who personally got ill after tick
      bite is associated with a good knowledge score and leads to higher susceptibility
      and better appreciation of the need for body checks. Perceived severity is
      associated with a good knowledge score and with knowing persons who got ill after
      tick-bite. Is seems to be useful to additionally address children in health
      education regarding ticks and tick-borne diseases. The relationship between
      health education programs for children (and their parents) about ticks and their
      possible consequences and prevention of these deserves further study.

PMID- 24321055
TI  - Gender-specific distribution of mefloquine in the blood following the
      administration of therapeutic doses.
AB  - BACKGROUND: The objectives of the study were to elucidate the gender-specific
      distribution of mefloquine in cellular and fluid blood compartments when given at
      therapeutic dosage, to assess its correlation with the occurrence of treatment
      related adverse events, and to explore the necessity of adjusting treatment
      guidelines for females. METHODS: The distribution of mefloquine following the
      administration of standard therapeutic doses (1,250 mg mefloquine in split dose)
      to 22 healthy Caucasian volunteers was assessed in whole blood, serum, plasma,
      red blood cells (RBCs), white blood cells, and platelets using high performance
      liquid chromatography. RESULTS: Plasma mefloquine concentrations after 14 hours
      were considerably higher in female subjects than in males (2,778 vs 1,017 ng/ml
      at H14), concordant with a significantly higher frequency, duration, and severity
      of adverse reactions. However, mean drug concentrations of RBC appeared slightly
      higher in male volunteers (857 vs 719 ng/ml). At H48, a similar situation
      prevailed, and at H168 the mefloquine concentrations in plasma continued to be
      higher in females compared to males (1,353 vs 666 ng/ml), while the
      concentrations of RBC were similar in females (389 vs 375 ng/ml). Since the
      observations relate to healthy individuals, they do not take into account
      selective uptake of mefloquine by Plasmodium-infected erythrocytes as in the case
      of therapeutic drug use. CONCLUSION: Although plasma mefloquine concentrations in
      female healthy volunteers are considerably higher and the concentrations of the
      RBCs are initially lower compared to males, they do not seem to justify an
      adjustment of treatment guidelines for mefloquine in female Caucasian
      individuals.

PMID- 24321056
TI  - SOS liver damage; calling all haematopoietic stem cells.

PMID- 24321057
TI  - Assessment of portal pressure in cirrhosis: how and when can we sedate?

PMID- 24321058
TI  - Steady-state kinetic isotope effects support a complex role of Arg226 in the
      proposed desulfonation mechanism of alkanesulfonate monooxygenase.
AB  - The alkanesulfonate monooxygenase system catalyzes the desulfonation of
      alkanesulfonates through proposed acid-base mechanistic steps that involves the
      abstraction of a proton from the alkane peroxyflavin intermediate and protonation
      of the FMN-O(-) intermediate. Both solvent and kinetic isotope studies were
      performed to define the proton transfer steps involved in the SsuD reaction.
      Substitution of the protium at the C1 position of octanesulfonate with deuterium
      resulted in an observed primary isotope effect of 3.0 +/- 0.2 on the kcat
      parameter, supporting abstraction of the alpha-proton from the alkane
      peroxyflavin as the rate-limiting step in catalysis. Previous studies implicated
      Arg226 as the acid involved in the reprotonation of the hydroxyflavin
      intermediate. Solvent isotope kinetic studies gave an inverse isotope effect on
      (D2O)kcat of 0.75 +/- 0.04 with no observable effect on (D2O)kcat/Km. This
      resulted in equivalent solvent isotope effects on (D2O)kcat and (D2O)(kcat)D,
      suggesting a solvent equilibrium isotope effect on a step occurring after the
      first irreversible step through product release. Data from proton inventory
      studies on kcat were best fit to a dome-shaped curve consistent with a
      conformational change to an open conformation during product release. The solvent
      isotope effect data coupled with the corresponding proton inventory results
      support and extend our previous observations that Arg226 donates a proton to the
      FMN-O(-) intermediate, triggering a conformational change that opens the enzyme
      to solvation and promotes product release. 

PMID- 24321059
TI  - Extragonadal sclerosing stromal tumor: a rare case report.
AB  - Sclerosing stromal tumor is a rare, benign, sex cord stromal tumor of the ovary.
      We report a case of extragonadal sclerosing stromal tumor in a 45-year-old woman
      who presented with menstrual irregularity and vague pelvic pain. Imaging studies
      showed a well-defined mass between the posterior wall of the bladder and uterus,
      suspected of being a pedunculated leiomyoma. The histopathological and
      immunohistochemical study was consistent with sclerosing stromal tumor. No
      ovarian tissue was found on representative sectioning. This is the first case of
      sclerosing stromal tumor in an extragonadal location. 

PMID- 24321061
TI  - Enhanced synthesis of 5-hydroxy-l-tryptophan through tetrahydropterin
      regeneration.
AB  - 5-Hydroxy-l-tryptophan (5-HTP) is a naturally occurring aromatic amino acid
      present in the seeds of the African plant Griffonia simplicifolia. Although 5-HTP
      has therapeutic effects in various symptoms, efficient method of producing 5-HTP
      has not been established. In this study, we developed a novel cofactor
      regeneration process to achieve enhanced synthesis of 5-HTP by using modified l
      phenylalanine 4-hydroxylase of Chromobacterium violaceum. For the synthesis of 5
      HTP using Escherichia coli whole cell bioconversion, l-tryptophan and 5-HTP
      degradation by E. coli endogenous catabolic enzymes should be considered. The
      tryptophanase gene was disrupted using the lambda red recombination system, since
      tryptophanase is postulated as an initial enzyme for the degradation of l
      tryptophan and 5-HTP in E. coli. For regeneration of the cofactor pterin, we
      screened and investigated several key enzymes, including dihydropteridine
      reductase from E. coli, glucose dehydrogenase from Bacillus subtilis, and pterin
      4alpha-carbinolamine dehydratase from Pseudomonas syringae. Genes encoding these
      three enzymes were overexpressed in an E. coli tryptophanase-deficient host,
      resulting in the synthesis of 0.74 mM 5-HTP in the presence of 0.1 mM pterin and
      the synthesis of 0.07 mM 5-HTP in the absence of regeneration of pterin. These
      results clearly indicated the successful regeneration of pterin. Following
      optimization of the reaction conditions, 2.5 mM 5-HTP was synthesized with
      cofactor regeneration, while 0.8 mM 5-HTP was recovered without cofactor
      regeneration under the same reaction conditions, suggesting that the principle
      described here provides a new method for cofactor regeneration. 

PMID- 24321062
TI  - [Relationship of reduced lung function with Th1/Th2 polarization, STAT4/6
      expression in rats of chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To study the correlations between lung function and Th1/Th2
      polarization, signal transducer and activator of transcription (STAT) proteins in
      rats of chronic obstructive pulmonary disease (COPD). METHODS: Sixty rats were
      randomly divided into normal control group, sham group and model group. The COPD
      rat models were developed by lipopolysaccharide (LPS). The changes of pulmonary
      function were detected at 28 d after modeling. The lung tissues of rats were
      observed by HE staining, and serum IFN-gamma, IL-4, IL-12, and IL-13 were
      determined by ELISA. The mRNA expressions of IFN-gamma and IL-4 were examined by
      PCR, and STAT4, STAT6 proteins in lung tissues were detected by Western blotting.
      RESULTS: Inflammation of lung tissues was more serious, the levels of serum IFN
      gamma, IL-12 and Th1/Th2, IFN-gamma mRNA and STAT4 protein in lung tissues were
      higher, and lung function, the levels of serum IL-4 and IL-13, IL-4 mRNA and
      STAT6 protein in lung tissues were lower in model group than those in normal
      control and sham groups (P < 0.05 or P < 0.01). Correlation analysis showed that
      there were negative correlations between pulmonary function parameters and IFN
      gamma, Th1/Th2, STAT4 protein, and positive correlations between pulmonary
      function parameters and IL-4, IL-13, IL-4 mRNA, STAT6 protein (P < 0.01 or P <
      0.05). CONCLUSION: The reduced lung function was found related to airway
      inflammation, cell Th1/Th2 imbalance in COPD. STAT4 and STAT6 involve in the
      regulation of Th1/Th2 cells. All of the above factors lead to the occurrence of
      COPD in rats.

PMID- 24321063
TI  - [Compound nutrients promote liver rehabilitation and regeneration in rats with
      CCl4;-induced liver cirrhosis].
AB  - OBJECTIVE: To explore the effects of compound nutrients on liver rehabilitation
      and regeneration in rats with CCl4;-induced liver cirrhosis. METHODS: The rat
      cirrhotic models were prepared by injecting intraperitoneally the mixture of
      CCl4; (40%) and oil (60%) by 2 mL/kg body weight twice a week for 12 weeks. The
      nutrition treatment group was treated with compound nutrients and the spontaneous
      recovery group was not treated with nutrients after stopping CCl4; injection.
      Then liver tissues and blood samples were harvested to detect the expressions of
      augmenter of liver regeneration (ALR) and proliferating cell nuclear antigen
      (PCNA) by immunohistochemistry, the level of hepatocyte growth factor (HGF) by
      ELISA, the levels of albumin (ALB), alanine aminotransferase (ALT), total
      bilirubin (TBIL), glucose, triglyceride (TG) and cholesterol (CHOL) by automatic
      biochemical analyzer, and the levels of amino acids in blood plasma by mass
      spectrometry. RESULTS: The expressions of ALR and PCNA were higher in nutrition
      treatment group than in spontaneous recovery group. The level of HGF in serum was
      higher in nutrition treatment group than in spontaneous recovery group (98.92 +/-
      2.42 vs 60.99 +/- 27.63, t = 3.349, P = 0.020). The levels of ALT (60.18 +/- 6.39
      vs 84.6 +/- 17.91, t = 3.146, P = 0.019) and TBIL (2.08 +/- 0.46 vs 6.97 +/-
      2.58, t = 4.56, P = 0.001) were lower in nutrition treatment group than in
      spontaneous recovery group. The level of ALB was higher in nutrition treatment
      group than in spontaneous recovery group (33.15 +/- 1.36 vs 24.62 +/- 2.48, t =
      7.39, P=0.000). The level of branched chain amino acids (BCAA) in blood plasma
      was higher in nutrition treatment group than in spontaneous recovery group
      (381.53 +/- 35.86 vs 283.05 +/- 79.14, t = 2.78, P = 0.02). CONCLUSION: Compound
      nutrients can be good for liver rehabilitation and regeneration in CCl4;-induced
      cirrhotic rat model, and the liver regeneration may relate to high BCAA level in
      blood plasma.

PMID- 24321064
TI  - [Reduning injection inhibits replication and proliferation of mouse
      cytomegalovirus and down-regulates the expressions of IFN-gamma and IL-6 in mouse
      cytomegalovirus pneumonia].
AB  - OBJECTIVE: To investigate the antiviral and immuno-regulatory effects of Reduning
      injection on mouse cytomegalovirus (MCMV) pneumonia. METHODS: BALB/c mice were
      divided randomly into five groups: blank control group, immunosuppressive control
      group, MCMV pneumonia group, Reduning treatment group, and ganciclovir treatment
      group. Acute MCMV interstitial pneumonia models were established in the latter
      three groups. Lung pathological changes were observed with HE staining, MCMV-DNA
      content in the lung tissue was detected by qRT-PCR, and the levels of interferon
      gamma (IFN-gamma) and interleukin-6 (IL-6) in the lung tissue were determined by
      ELISA. RESULTS: Compared with MCMV pneumonia group, the lung injuries in Reduning
      treatment and ganciclovir treatment groups were ameliorated, and the MCMV-DNA
      expression in the two treatment groups decreased, and the changes in ganciclovir
      treatment group were more obvious (P < 0.05). Compared with MCMV pneumonia group,
      the levels of IFN-gamma and IL-6 in Reduning treatment group rose by 1.4 times
      and dropped by 30.2%, respectively; and IFN-gamma increased by 1.6 times and IL-6
      decreased by 47.6% in ganciclovir treatment group (P < 0.05); the differences
      between the two treatment groups were statistically significant (P < 0.05). IFN
      gamma/IL-6 ratio in Reduning treatment group was higher than that in MCMV
      pneumonia group, and approached the level of immunosuppressive control group.
      CONCLUSION: Reduning injection might exert antiviral activity through inhibiting
      MCMV replication and proliferation in lung tissue directly, and down-regulating
      the expressions of IFN-gamma and IL-6.

PMID- 24321065
TI  - [The combined effects of insulin and selenium in improving insulin signal
      transduction in skeletal muscles of diabetic rats].
AB  - OBJECTIVE: To investigate the combined effects of insulin and selenium in
      improving the physiological parameters and insulin signal transduction in the
      skeletal muscles of diabetic rats. METHODS: 35 male SD rats were randomly divided
      into five groups: normal, diabetes, diabetes with insulin treatment (D-In group),
      diabetes with sodium selenite treatment (D-In-S group), and diabetes with insulin
      and sodium combination treatment (D-In-Se group), 7 rats in each group. The
      levels of blood glucose were measured using One Touch Sure Step Blood Glucose
      Meter. HbA1C levels were measured using microcolumn assay. The levels of insulin
      receptor substrate 1(IRS-1), phosphatidylinositol-3 kinase (PI3K) and glucose
      transporter 4(GLUT4) in skeletal muscle were examined by Western blotting and
      immunohistochemistry. RESULTS: Insulin combined with selenium could significantly
      lower blood glucose levels and markedly restore the diminished expression of in
      IRS-1, PI3K and GLUT4 levels in skeletal muscles of diabetic rats. CONCLUSION:
      There was positive cooperativity between insulin and selenium in reducing blood
      glucose levels in diabetic rats. The combined treatment of insulin and selenium
      may decrease blood glucose by upregulating IRS-1, PI3K and GLUT4 levels in
      skeletal muscles of diabetic rats.

PMID- 24321066
TI  - [Immune regulatory effect of citalopram on microglial cells].
AB  - OBJECTIVE: To investigate the effects of antidepressant citalopram on the gene
      expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL
      1beta), and to discuss the impacts of citalopram on p38 and c-jun N-terminal
      kinase (JNK) of mitogen-activated protein kinase (MAPK) family in microglial
      cells. METHODS: BV2 cells were induced by lipopolysaccharide (LPS) to produce TNF
      alpha and IL-1beta. After pretreatment with citalopram (20 MUmol/L) for 4 h, the
      mRNA levels of TNF-alpha and IL-1beta were measured by quantitative real-time PCR
      (qRT-PCR); after pretreatment for 24 h, the protein levels of TNF-alpha and IL
      1beta were analyzed by ELISA; the effects of citalopram on the phosphorylation of
      p38MAPK and JNK were observed after pretreatment for 30 min. RESULTS: Citalopram
      significantly inhibited the mRNA and protein expressions of TNF-alpha and IL
      1beta, and the phosphorylation of p38MAPK and JNK. CONCLUSION: Citalopram may
      play the anti-inflammatory role by inhibiting MAPK pathway in microglial cells.

PMID- 24321067
TI  - [Role of oxidized low-density lipoprotein in NF-kappaB signal pathway].
AB  - OBJECTIVE: To explore the effects of oxidized low-density lipoprotein (ox-LDL) on
      P65, P50, tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) of
      human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were randomly
      divided into several groups as follows: the control group, the ox-LDL stimulated
      groups (different concentrations: 15, 30, 60, 120 MUg/mL ox-LDL stimulation for
      24 hours, and 30 MUg/mL ox-LDL stimulation for different time periods: 12, 24, 48
      hours), and the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC)
      intervention group (100 MUmol/L PDTC pretreatment for 1 h before 30 MUg/mL ox-LDL
      stimulation for 24 hours). Nucleoprotein was extracted to detect P65 and P50
      protein expression of NF-kappaB signaling pathway by Western blotting, and the
      concentrations of TNF-alpha and IL-6 in cell supernatants were measured by ELISA.
      RESULTS: Western blotting showed that the expressions of P65 and P50 increased
      under the induction of ox-LDL in a time- and concentration-dependent manner, and
      the differences were statistically significant among groups (P < 0.05), while
      they were reduced significantly by PDTC intervention (P < 0.05). ELISA showed
      that the concentrations of TNF-alpha and IL-6 in the supernatants of HUVECs
      stimulated by ox-LDL for 24 hours were significantly higher than those in the
      control group, while they were reduced significantly by PDTC intervention. There
      were significant statistical differences among the different treated groups (P <
      0.05). CONCLUSION: Ox-LDL can enhance the activity of NF-kappaB signaling pathway
      in a time- and concentration-dependent manner through increasing the expressions
      of TNF-alpha and IL-6.

PMID- 24321068
TI  - [Preparation and characterization of the recombinant hFGF21-containing
      lentiviral].
AB  - OBJECTIVE: To package the lentiviral particles carrying human fibroblast growth
      factor 21 (hFGF21) and identify the morphological characteristics and
      transduction capability for the target gene of human embryo kidney 293T (HEK293T)
      cells. METHODS: After sequencing identification, the lentiviral recombinant
      plasmid Lv105-hFGF21 was packaged and concentrated in HEK293T cells, and then
      identified by RT-PCR and electron microscopy. The titer of recombinant lentivirus
      was determined by real-time quantitative PCR. The expression of hFGF21 at both
      mRNA and protein levels was detected by RT-PCR and immunofluorescence,
      respectively in lentivirus-infected Vero cells. RESULTS: RT-PCR demonstrated that
      hFGF21 mRNA could be transcribed in Lv105-hFGF21 infected HEK293T cells. The
      typical lentiviral particle was seen under the electron microscope. The diameter
      of virus particles was 40-70 nm. The title of the virus was substantially
      elevated from 3.68 * 10(8); VG/mL to 1.25 * 10(9); VG/mL after concentration. The
      expression of hFGF21 was detected in Lv-hFGF21 infected Vero cells by means of
      both RT-PCR and immunofluorescence. CONCLUSION: The hFGF21 lentiviral particles
      have been packaged successfully and hFGF21 can be expressed in the infected Vero
      cells.

PMID- 24321069
TI  - [RANKL and OPG expression in bone marrow-derived mesenchymal stem cells of
      ovariectomied promotes osteoclast development and enhances its function].
AB  - OBJECTIVE: To investigate the expression of receptor activator of nuclear factor
      kappa B lig (RANKL), osteoprotegerin (OPG) in bone marrow mesenchymal stem cells
      (BMSCs) and its impact on osteoclast formation and function in the ovariectomied
      mice. METHODS: An animal model of osteoporosis was established by ovariectomy
      (OVX bilateral ovarian resection) in 8-week-old healthy female mice. The sham
      group was the 8-week-old healthy female mice with bilateral resection.
      Macrophages from mice were inducted by M-CSF and RANKL, and co-cultured with the
      BMSCs collected from mice in the OVX group and sham group, respectively. The
      osteoclast numbers of the two groups were compared by TRAP staining. The
      resorption pits were measured by toluidine blue staining. The level of RANKL/OPG
      expression was detected by RT-PCR and Western blotting. RESULTS: TRAP assay and
      toluidine blue staining showed that the numbers of osteoclasts and resorption
      pits in OVX group were more than that in the sham group. The expression of RANKL
      in BMSC was lower in sham group than that of the OVX group. On the contrary, the
      expression of OPG in BMSCs was higher in the shame group than that of the OVX
      group. CONCLUSION: Expression of RANKL/OPG are regulated by estrogen in BMSCs.
      RANKL and OPG expression promotes osteoclast development and enhances its
      function under the condition of estrogen deficiency.

PMID- 24321070
TI  - [Role of bone marrow-derived mesenchymal stem cells in treating estrogen
      deficiency induced osteoporosis].
AB  - OBJECTIVE: To investigate the therapeutic effects of bone marrow-derived
      mesenchymal stem cells (BMSCs) from C57BL/6 mice on estrogen deficiency induced
      osteoporosis. METHODS: Mouse models of estrogen deficiency induced osteoporosis
      were set up through ovariectomy (OVX) operation and sham operation group was set
      up as controls. BMSCs were injected via caudal veins. Micro-CT scanning of the
      femurs was conducted to detect the therapeutic effects of BMSCs. ELISA was used
      to test the expression level of TNF-alpha in serum before and after the injection
      of BMSCs. In the meantime, T cell apoptosis was also tested by flow cytometry
      combined with FITC-annexin V/7-amino actimycin D staining. RESULTS: Compared with
      the sham operation group, the trabecular volume (BV/TV), bone mineral density
      (BMD) and trabecular number (Tb.N/mm) of osteoporosis mice set up by OVX were
      reduced significantly, and serum TNF-alpha was up-regulated a little. After the
      injection of BMSCs, the BV/TV, Tb.Th, Tb.N and T cell apoptosis in the
      osteoporosis mice increased, and the level of TNF-alpha decreased. CONCLUSION:
      With the ability of immunoregulation, BMSCs might play a critical role in
      treating estrogen deficiency induced osteoporosis.

PMID- 24321071
TI  - [The effect of leptin and its mechanisms on the migration and invasion of human
      breast cancer MCF-7 cells].
AB  - OBJECTIVE: To investigate the effect and the relevant molecular mechanisms of
      leptin on the migration and invasion of human breast cancer MCF-7 cells. METHODS:
      The expression of OB-R in MCF-7 cells was measured by RT-PCR and Western
      blotting. The effects of leptin (100 ng/mL) on the the phosphorylation of a few
      key cell signaling proteins, p-ERK1/2, p-STAT3, p-AKT in MCF-7 cells were
      examined by Western blotting. Cell scratch assay and Transwell(TM); assay were
      utilized to measure the effects of leptin on the migration and invasion
      capability of MCF-7 cells, respectively. The effects of leptin on the mRNA and
      protein expression of matrix metalloproteinas 9 (MMP-9) and transforming growth
      factor beta (TGF-beta) were measured by RT-PCR and Western blotting. RESULTS:
      Both OB-Rb and OB-Rt were expressed in MCF-7 cells. This indicated that leptin
      may have significant activities in MCF7 cells. Indeed, leptin increased the
      phosphorylation of p-ERK1/2, p-STAT3, and p-AKT in MCF-7 cells (P < 0.05).
      Further, leptin promoted migration and invasion of MCF-7 cells, which were
      attenuated by the JAK/STAT inhibitor AG490 (50 MUmol/L), and the PI3K/AKT
      inhibitor LY294002 (10 MUmol/L) (P < 0.05). Similarly, leptin also increased the
      mRNA and protein expression of MMP-9 and TGF-beta, and these effects were blocked
      by AG490 and LY294002 as well (P < 0.05). CONCLUSION: Leptin promoted the
      migration and invasion capabilities of MCF-7 cells. These activities may be
      achieved by the upregulation of MMP-9 and TGF-beta through JAK/STAT and PI3K/AKT
      signaling pathways.

PMID- 24321072
TI  - [Overexpression of Wnt3a inhibited the apoptosis of mouse embryonic liver stem
      cells].
AB  - OBJECTIVE: To study the effect of Wnt3a on the apoptosis and the expressions of
      apoptosis-related proteins in mouse embryonic liver stem cells (ELSCs). METHODS:
      The mouse ELSC14.5 cells were randomly divided into two groups: control group and
      experimental group, which were infected with two adenovirus vectors expressing
      green fluorescent protein, Ad-GFP and Ad-GFP-wnt3a, respectively. The mRNA and
      protein expressions of Wnt3a and apoptosis-related factors Bcl-2, Mcl-1 and Bax
      were examined by real-time quantitative PCR (qRT-PCR) and Western blotting
      respectively. Cell apoptosis was tested by annexin-PE/7-ADD and Hoechst 33258
      staining method. RESULTS: qRT-PCR and Western blotting showed Wnt3a was
      effectively expressed in ELSC14.5 cells, indicating the adenovirus vector Ad
      Wnt3a had been successfully transferred into the targeted cells. Compared with
      the control group, the experimental group presented the increased mRNA and
      protein expressions of the anti-apoptotic factor Bcl-2 and Mcl-1, and the
      decreased expression of pro-apoptotic factor Bax (P < 0.05). Hoechst 33258
      staining method combined with annexin-PE/7-ADD method showed that the ELSC14.5
      cells highly expressing Ad-Wnt3a, whose nuclei were dense, hyperchromatic, or
      fragmented, were very rare, and that the rate of cell apoptosis was reduced.
      CONCLUSION: Wnt3a inhibites the mouse ELSC apoptosis by up-regulating the Bcl-2
      family's anti-apoptotic and down-regulating pro-apoptotic factors to prolong its
      survival.

PMID- 24321073
TI  - [An increased of Th17 cells and IL-23 and IL-17 in the lymph and blood of rats
      with bronchial asthma].
AB  - OBJECTIVE: To investigate whether immune response could change the number of
      CD4(+);IL-17(+);Th17 cells and the concentrations of IL-17 and IL-23 in the serum
      and lymph of asthmatic rats. METHODS: Both serum and lymph CD4(+);IL-17(+);Th17
      cell numbers were measured by flow cytometry. The concentrations of IL-17 and IL
      23 in the serum and lymph were assayed by ELISA. The expression of IL-23 p19 mRNA
      was examined by quantitative real-time PCR. RESULTS: Mononuclear cells (MNC) were
      collected from the blood and lymph of rats 0, 24 and 48 hours after final
      ovalbumin stimulation and were subsequently cultured for 18 hours. The serum and
      lymph of the asthma group produced higher amounts of CD4(+);IL-17(+);Th17 cells,
      and higher levels of IL-23p19 mRNA, than those of the healthy controls (P <
      0.05). In addition, compared to lymph, serum had significantly lower amounts of
      CD4(+);IL-17(+);Th17 cells, decreased expression of IL-23p19 mRNA, and reduced IL
      23 and IL-17 concentratons (P < 0.05). Cytokines and cell numbers of Th17 cells
      from the asthma group significantly increased compared with that of control
      group. CONCLUSION: These data suggested that asthma-driven CD4(+);IL-17(+);Th17
      cell proliferation and release of IL-17 and IL-23 may be associated with
      different immune activities between the serum and lymph.

PMID- 24321074
TI  - [Preparation and characterization of monoclonal antibodies against FlhF protein
      of Campylobacter jejuni].
AB  - OBJECTIVE: To develop a prokaryotic expression system for Campylobacrer jejuni
      FlhF protein and prepare monoclonal antibodies(mAb) against this protein.
      METHODS: The C. jejuni flhF gene was amplified and inserted into the expression
      plasmids, pET-30a(+) and pGEX-6p-1. Then the rHis-FlhF protein and rGST-FlhF
      protein were expressed and purified by affinity column chromatography. They were
      subsequently used as immunogen and detecting antigen to screen antibodies
      produced by hybridoma cells against these proteins. The titers of the mAbs were
      measured by indirect ELISA, and the specificities of the mAbs was evaluated by
      Dot-ELISA and Western blot analysis. RESULTS: The recombinant expression plasmids
      pET-30a(+)-flhF and pGEX-6p-1-flhF were successfully constructed, and the fusion
      proteins rHis-FlhF and rGST-FlhF were produced at sufficient quantities. Two
      hybridoma cell lines were screened, designated 2C12 and 7A9, which secrete mAbs
      against FlhF stably. Their immunoglobulin subclasses were both IgG1. The titers
      of the ascites fluid were 1*10(9); and 2*10(7); respectively. Western blot
      analyses confirmed that the two mAbs both reacted with the rHis-FlhF fusion
      protein with good sensitivity. The Dot-ELISA results demonstrated that the two
      mAbs reacted specifically with Campylobacrer jejuni. CONCLUSION: The mAbs against
      Campylobacrer jejuni FlhF protein with high specificity were successfully
      prepared.

PMID- 24321075
TI  - [Preparation and biological activity analysis of chimeric antibody against
      capsular F1 antigen of Yersinia pestis].
AB  - OBJECTIVE: To express human-mouse chimeric antibody against Yersinia pestis F1
      capsular antigen (F1 antigen) and analyze its biological activities. METHODS: The
      heavy chain gene of the chimeric antibody was obtained by fusing the variable
      region gene of the mouse mAb heavy chain with human IgG1 constant region gene.
      The light chain gene of the chimeric antibody was obtained by fusing the variable
      region gene of the mouse mAb light chain with the human kappa constant region
      gene. Both the heavy and light chain genes of the chimeric antibody were further
      verified by sequencing. The chimeric antibody heavy and light chain genes were
      inserted into EcoR I/Not I of pcDNA3.1 (+) to construct expression plasmids
      termed pcDNA3.1-L and pcDNA3.1-H, respectively. Then, two plasmids were mixed and
      transfected into CHO-S cells. Finally, the stable cell clone secreting chimeric
      antibody was obtained by G418 selection. The culture supernatants of serum-free
      medium were collected and the chimeric antibody was purified by MabSelect SuRe
      affinity chromatography. The purified chimeric antibody was analyzed by SDS-PAGE,
      Western blotting, ELISA and evaluated in the protective effect in vivo. RESULTS:
      PCR and sequencing analysis proved that plasmids pcDNA3.1-H and pcDNA3.1-L were
      correctly constructed. Dot blot showed that a cell line with high-level
      expression of chimeric antibody was obtained. SDS-PAGE and western blot showed
      that the chimeric antibody was successfully purified. ELISA showed that the
      chimeric antibody could specifically bind to F1 antigen. In vivo activity assay
      showed that 80% BALB/c mice treated with the chimeric antibody survived from 36
      MLD virulent Yersinia pestis. CONCLUSION: The chimeric antibody against F1
      antigen with neutralizing activity was successfully expressed in CHO-S cells,
      which laid a foundation for the preparation of anti-plague passive immunity
      agents.

PMID- 24321076
TI  - [The percentage of regulatory T cells in peripheral blood of chronic lymphocytic
      leukemia patients and the correlations with clinical prognosis].
AB  - OBJECTIVE: To explore the percentage of CD4(+);CD25(+);Foxp3(+); regulatory T
      cells (Treg) in peripheral blood of chronic lymphocytic leukemia (CLL) patients
      and the correlations with clinical prognosis. METHODS: The study enrolled 30
      healthy individuals and 28 CLL patients. The CD4(+);CD25(+); Treg and
      CD4(+);CD25(+);Foxp3(+); Treg were detected by the flow cytometry in their
      peripheral blood. Of the 28 CLL patients, 19 received treatment and follow-up.
      RESULTS: The number of CD4(+);CD25(+); Treg in the pre-treated cases (n = 28) was
      higher than that in the healthy controls (n = 30) with significant statistical
      difference (P < 0.05). The number of CD4(+);CD25(+);Foxp3(+); Treg was higher in
      the pre-treated cases (n = 28) than that in the treated cases (n = 19) and in the
      healthy controls (n = 30) (P < 0.05). Compared with the healthy controls, the
      treated cases (n = 19) had the higher level of CD4(+);CD25(+);Foxp3(+); Treg (P <
      0.05). The CD4(+);CD25(+);Foxp3(+); Treg was positively correlated with the
      expressions of CD38, beta2-microglobulin (beta(2);-MG), zeta-associated protein
      70(ZAP-70) and the clinical Binet and Rai stages. CONCLUSION: The
      CD4(+);CD25(+);Foxp3(+); Treg might be a valuable indicator for assessing the
      therapeutic efficacy, disease progression and prognosis of the CLL patients.

PMID- 24321077
TI  - [Isolation, primary culture and characterization of mouse glomerular mesangial
      cells].
AB  - OBJECTIVE: To establish a method for the isolation, primary culture and
      characterization of mouse mesangial cells (MCs). METHODS: We used two-layer
      micropore filter device to isolate glomeruli, and the MCs were cultured with
      eugenic selection method. Cell structures of MCs were observed by inverted phase
      contrast microscope, HE staining, scanning electron microscope and transmission
      electron microscope. Expressions of alpha-smooth muscle actin (alpha-SMA and
      nephrin were investigated by immunofluorescent cytochemistry. We used angiotensin
      II to stimulate MCs and observed the biological characteristics of the cells. The
      growth curve of MCs was examined by CCK-8 assay. RESULTS: After 20-30 days, the
      primary cultured MCs gradually covered the bottom of the dish. The mouse MCs
      usually attached to the surface 6-10 hours after passage, followed by the
      exponential phase in 2-3 days and the platform period in 3-5 days.
      Immunofluorescent staining showed that the expression of alpha-SMA was positive
      and nephrin was negative. MCs contraction was observed after the cells were
      stimulated by angiotensin II for 15 minutes. CONCLUSION: A method for the
      isolation, culture and characterization of mouse mesangial cells has been
      successfully established.

PMID- 24321078
TI  - [Prediction of the B cell epitopes of hemagglutinin and neuraminidase of human
      infected avian influenza A H7N9 virus].
AB  - OBJECTIVE: To predict the B cell epitopes of hemagglutinin (HA) and neuraminidase
      (NA) of human-infected avian influenza A H7N9 virus by bioinformatics software.
      METHODS: The B cell epitopes of HA and NA proteins were predicted comprehensively
      by bioinformatics software such as Protean, PORTER, MEGA based on the amino acid
      sequences of HA and NA, and further screened by Wu Yuzhang's average antigen
      index strategies. RESULTS: The most possible epitopes of HA were located on its N
      terminal No. 53-57, 179-183. The N-terminal No. 62-66, 98-101, 164-166, 315-320,
      424-426, 443-445, 493-496 might have the B cell epitopes of HA protein. The most
      possible epitopes of NA were located on its N-terminal No. 321-329, 379-386.
      There were possible B cell epitopes located on the N-terminal No. 46-48, 52-54,
      74-78, 136-141, 145-150, 160-164, 194-197, 246-248, 333-343, 426-431. CONCLUSION:
      The prediction of B cell epitopes of HA and NA proteins with multiple methods
      benefits the research and development of B cell epitope vaccine against human
      infection with avian influenza A H7N9 virus.

PMID- 24321079
TI  - [An indirect ELISA using Legionella pneumophila recombinant MOMP protein and its
      application in serological diagnosis].
AB  - OBJECTIVE: To express and purify the recombinant major outer membrane protein
      (MOMP) of Legionella pneumophila (Lp) as diagnostic antigen, and explore its
      practical value in the serological diagnosis of Lp infection. METHODS: The
      recombinant plasmid pET-momp was transformed into the E.coli BL21 competent
      cells. The recombinant MOMP was induced to express, and then analyzed by SDS-PAGE
      electrophoresis, purified by affinity chromatography. We screened and obtained 58
      positive blood serum and 32 negative blood serum using the DRG (Germany,
      IgG/IgM/IgA) Lp kit. The blood serum samples were detected for IgG, IgM, IgA
      antibody levels by indirect ELISA that we had established with the purified MOMP
      as the coating antigen, as well as by R&D (USA, IgG/IgM/IgA) Lp kit. Then using
      the receiver operating characteristic (ROC) curve, we compared these two methods
      in the sensitivity, specificity and consistency of the test results, for
      evaluating the application value of the indirect ELISA of recombinant MOMP.
      RESULTS: The approximately 45 000 recombinant MOMP was successfully expressed and
      purified. Compared with the indirect ELISA we established with the R&D Lp kit for
      detecting Lp antibody IgG, IgM and IgA in blood serum, the sensitivity of the
      indirect ELISA of recombinant MOMP to IgG was 90.9%, the specificity was 91.7%,
      the Kappa value was 0.784 (P < 0.05), and the area under the ROC curve was 0.913;
      the sensitivity to IgM was 91.4% and the specificity was 90.6%, the Kappa value
      was 0.809 (P < 0.05), and the area under the ROC curve was 0.910; the sensitivity
      to IgA was 92.1% and the specificity was 88.9%, the Kappa value was 0.793(P <
      0.05), and the area under the ROC curve was 0.905. CONCLUSION: The recombinant
      MOMP was successfully induced to express and purified. The indirect ELISA we
      established with the recombinant MOMP protein as a diagnostic antigen showed good
      specificity, sensitivity and consistency, which laid a foundation for the
      development of serological diagnosis kit of Legionnaires' disease.

PMID- 24321080
TI  - Lipids in metabolic diseases.

PMID- 24321081
TI  - Brain-computer interface controlled robotic gait orthosis.
AB  - BACKGROUND: Excessive reliance on wheelchairs in individuals with tetraplegia or
      paraplegia due to spinal cord injury (SCI) leads to many medical co-morbidities,
      such as cardiovascular disease, metabolic derangements, osteoporosis, and
      pressure ulcers. Treatment of these conditions contributes to the majority of SCI
      health care costs. Restoring able-body-like ambulation in this patient population
      can potentially reduce the incidence of these medical co-morbidities, in addition
      to increasing independence and quality of life. However, no biomedical solution
      exists that can reverse this loss of neurological function, and hence novel
      methods are needed. Brain-computer interface (BCI) controlled lower extremity
      prostheses may constitute one such novel approach. METHODS: One able-bodied
      subject and one subject with paraplegia due to SCI underwent electroencephalogram
      (EEG) recordings while engaged in alternating epochs of idling and walking
      kinesthetic motor imagery (KMI). These data were analyzed to generate an EEG
      prediction model for online BCI operation. A commercial robotic gait orthosis
      (RoGO) system (suspended over a treadmill) was interfaced with the BCI computer
      to allow for computerized control. The subjects were then tasked to perform five,
      5-min-long online sessions where they ambulated using the BCI-RoGO system as
      prompted by computerized cues. The performance of this system was assessed with
      cross-correlation analysis, and omission and false alarm rates. RESULTS: The
      offline accuracy of the EEG prediction model averaged 86.30% across both subjects
      (chance: 50%). The cross-correlation between instructional cues and the BCI-RoGO
      walking epochs averaged across all subjects and all sessions was 0.812 +/- 0.048
      (p-value <10(-4)). Also, there were on average 0.8 false alarms per session and
      no omissions. CONCLUSION: These results provide preliminary evidence that
      restoring brain-controlled ambulation after SCI is feasible. Future work will
      test the function of this system in a population of subjects with SCI. If
      successful, this may justify the future development of BCI-controlled lower
      extremity prostheses for free overground walking for those with complete motor
      SCI. Finally, this system can also be applied to incomplete motor SCI, where it
      could lead to improved neurological outcomes beyond those of standard
      physiotherapy.

PMID- 24321082
TI  - Procedural justice and the judge-probationer relationship in a co-occurring
      disorders court.
AB  - Although a considerable amount of research has been conducted on treatment-based
      courts, there is little quantitative evidence that describes the relationship
      between the judge and the probationer. The present study examines perceptions of
      the judge-probationer relationship (JPR), procedural justice, and outcome
      satisfaction within a co-occurring disorders court (CODC) in Orange County,
      California. Based on interview and survey data from a sample of probationers
      within the CODC (n=24), this article argues that perceptions of procedural
      justice are linked to perceptions of relationship quality between the judge and
      probationer. Analysis of the data found that probationers in the CODC have very
      positive views of their relationships with the judge, and elements of
      relationship quality are significantly linked with perceptions of procedural
      justice. Procedural justice is also a predictor of satisfaction with outcome in
      this sample. The results show promise that procedural justice and the quality of
      the judge-probationer relationship can positively affect probationers with co
      occurring disorders in specialty courts. 

PMID- 24321083
TI  - The impact of judge-defendant communication on mental health court outcomes.
AB  - Previous research has shown that mental health courts have been successful in
      reducing the rates of recidivism among mentally ill offenders. However, none of
      these studies, to date, have examined exactly what aspects of the courts reduce
      these rates of recidivism and what makes them successful. The current study
      utilized a sample of 291 mentally ill criminal offenders participating in a
      mental health court to examine whether those participants who were addressed by
      and communicated with the judge had a reduction in recidivism rates and the
      severity of new charges in comparison to those who did not. The hypotheses
      regarding greater judge-defendant communication and recidivism were not
      supported. This suggests that communication in and of itself is not sufficient to
      reduce recidivism. Future research of a qualitative nature is essential to
      identify if the frequency, tone, and valence of the communication results in
      improved outcomes. In addition, these results may indicate a necessity for more
      stringent training and guidelines for the maintenance of Mental Health Courts.
      Results of the current study suggested differences between genders, such that
      females were spoken to by the judge more frequently than were men. 

PMID- 24321084
TI  - A mixed quantum-classical molecular dynamics study of anti-tetrol and syn-tetrol
      dissolved in liquid chloroform: hydrogen-bond structure and its signature on the
      infrared absorption spectrum.
AB  - The intramolecular hydrogen-bond structure of stereoselectively synthesized syn
      tetrol and anti-tetrol dissolved in deuterated chloroform is investigated via a
      mixed quantum-classical molecular dynamics simulation. An extensive
      conformational analysis is performed in order to determine the dominant
      conformations, the distributions among them, and their sensitivity to the method
      for assigning partial charges (RESP vs AM1-BCC). The signature of the
      conformational distribution and method of assigning partial charges on the
      infrared absorption spectra is analyzed in detail. The relationship between the
      spectra and the underlying hydrogen-bond structure is elucidated. 

PMID- 24321085
TI  - Rapid prenatal diagnosis of common numerical chromosomal abnormalities by high
      resolution melting analysis of segmental duplications.
AB  - BACKGROUND: Rapid aneuploidy detection (RAD) methods constitute important
      complements to karyotyping in prenatal diagnosis. We evaluated the effectiveness
      of a method called high-resolution melting analysis of segmental duplications (SD
      HRM) to serve as an alternative RAD method in prenatal diagnosis of common
      numerical chromosomal abnormalities (NCAs). METHODS: We designed eight primary SD
      HRM assays for the detection of chromosomes 13, 18, 21, X, and Y; 50 chorionic
      villus, 1105 amniotic fluid, and 395 cord blood samples were examined using these
      eight assays. For diagnosing samples that could not be diagnosed using primary
      assays, additional assays were designed for each target chromosome. RESULTS: The
      success rate of eight primary SD-HRM assays ranged from 99.7% to 100%. For the
      distinguishable analyses, these eight assays attained high diagnostic
      sensitivities (100%) and specificities (99.9-100%). We differentiated 53 cases of
      NCAs from 1550 clinical samples; subsequent reference tests revealed that these
      assays attained 100% clinical sensitivity and specificity. The mosaic ratio of a
      45,X/46,XX sample was also precisely calculated. CONCLUSIONS: The SD-HRM method
      was able to effectively detect common NCAs in 1550 prenatal samples. We propose
      that SD-HRM could serve as an effective alternative option to the currently used
      prenatal RAD methods.

PMID- 24321086
TI  - [Fever and thrombocytopenia in a 40-year-old man].

PMID- 24321087
TI  - [Serious clinical manifestations of vitamin deficiency after a "sleeve"
      gastrectomy: role of psychogenic anorexia].
AB  - INTRODUCTION: Morbid obesity is an emerging condition in the general population.
      Bariatric surgery, which has demonstrated its effectiveness for weight loss,
      mortality and morbidity related to obesity, is required in some patients.
      However, it may be associated with various adverse effects, including vitamin
      deficiencies. CASE REPORT: We report a 33-year old man who presented central and
      peripheral neurological deficits and cardiac manifestations related to multiple
      vitamin deficiencies, following "sleeve" gastrectomy. The vitamin deficiencies
      were related to insufficient ingesta secondary to psychogenic anorexia. The
      patient improved with vitamins, antidepressant drugs and atypical neuroleptics.
      CONCLUSION: Post-operative complications of "sleeve" gastrectomy include vitamin
      deficiencies that can develop in the context of psychogenic anorexia and ingesta
      reduction, in the absence of any digestive malabsorption.

PMID- 24321088
TI  - [Infectious thoracic aortic aneurysms: 7 cases and literature review].
AB  - PURPOSE: Infectious aortic aneurysms are rare conditions, being responsible of 2%
      of aortic aneurysms. Most published results are surgical case series concerning
      infected abdominal aorta. In this retrospective study, we assessed clinical
      features and outcome of patients presenting infectious thoracic aortic aneurysms.
      PATIENTS AND METHODS: Diagnosis was based upon a combination of imaging evidence
      for thoracic aorta aneurysm and evidence for an infective aetiology including a
      culture of a causative pathogen, or a favourable outcome with anti-infective
      therapy. Retrospective case series. RESULTS: Six men and one woman were included,
      with a mean age of 66 years. All the patient presented at least one
      cardiovascular risk factor or atherosclerosis localisation. Fever (71%) and chest
      pain (42%) were the most common clinical presenting manifestations. The causative
      pathogens were: Staphylococcus aureus (N=1), Salmonella enteritidis (N=3) and
      Candida albicans (N=1). The contrast-enhanced computed-tomography disclosed an
      aneurysm whose diameter reached more than 50 mm (N=5), that increased rapidly in
      size (N=5), or presented an inflammatory aspect of the aortic wall (N=4).
      Management was both medical and interventional: surgery (N=3) or endoluminal
      repair (N=4). Outcome was favourable in six patients; one patient died from
      aneurysm-related complications. CONCLUSION: Clinical manifestations revealing an
      infectious thoracic aneurysm are variable. Diagnosis should be considered in
      patients presenting a rapidly-growing aneurysm, especially in the presence of
      elevated acute phase reactants. Endoluminal repair constitutes a treatment
      option. The role of FDG-PET for diagnosis and follow-up remains to be defined.

PMID- 24321089
TI  - Inhibition of tumour angiogenesis and growth by small hairpin HIF-1alpha and IL-8
      in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Hypoxia-inducible factor-1alpha (HIF-1alpha), a key
      transcription factor in the cellular response to hypoxia, and interleukin 8 (IL
      8), a key mediator of angiogenesis, are important in cancerous tumour growth. In
      this study, we evaluated the effects of HIF-1alpha and IL-8 knockdown on
      angiogenesis and tumour growth in hepatocellular carcinoma (HCC). METHODS:
      Hepatocellular carcinoma cell lines were infected with adenoviruses expressing
      small-hairpin RNA (shRNA) specific for HIF-1alpha or IL-8, cultured under hypoxic
      conditions (1% O2), and examined for their levels of HIF-1alpha, IL-8, and
      angiogenesis factors using immunoblot. The effects of adenovirus-mediated shRNA
      induced HIF-1alpha and IL-8 knockdown on tumour growth and angiogenesis were also
      investigated in a subcutaneous Hep3B-tumour mouse model. RESULTS: Hypoxia
      inducible factor-1alpha knockdown directly repressed tumour growth, whereas IL-8
      knockdown indirectly repressed tumour growth. Combined knockdown of HIF-1alpha
      and IL-8 increased survival rates of mice. HIF-1alpha and IL-8 knockdown also
      decreased microvessel density and tumour volume in vivo. Similarly, HIF-1alpha
      and IL-8 knockdown inhibited the angiogenic effects of HCC cell-conditioned media
      on tube formation and invasion by endothelial cells in vitro. CONCLUSION: These
      findings indicate that shRNA-induced HIF-1alpha and IL-8 knockdown inhibit
      angiogenesis and tumour growth in HCC. Further development of HIF-1alpha and IL-8
      shRNA technologies could lead to effective therapies for HCC.

PMID- 24321090
TI  - Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in
      mice.
AB  - BACKGROUND: Saturated fatty acids are thought to be of relevance for the
      development of non-alcoholic fatty liver disease and obesity. However, the
      underlying mechanisms are poorly understood. In previous studies we found that
      food-derived carbohydrates such as fructose alter the intestinal serotonergic
      system while inducing fatty liver disease in mice. Here, we examined the effect
      of fatty acid quantity (11% versus 15%) and quality (saturated, monounsaturated,
      or polyunsaturated fatty acids) on hepatic fat accumulation, intestinal barrier
      and the intestinal serotonergic system. METHODS: C57BL/6 mice had free access to
      diets enriched with one of the three fatty acids or standard diet, for 8 weeks.
      In an additional experiment mice were fed diets enriched with saturated,
      monounsaturated fatty acids or standard diet supplemented with tryptophan (0.4
      g/(kg.d), 8 weeks) or not. Hepatic fat accumulation, small intestinal barrier
      impairment and components of the serotonergic system were measured with RT-PCR,
      western blot or immunoassays. For statistical analysis t-test and one-way ANOVA
      with Tukey's post hoc test and Bartlett's test for equal variances was used.
      RESULTS: Hepatic triglycerides, liver weight and liver to body weight ratio were
      significantly changed depending on the fat quality but not fat quantity. In
      contrast, fat quantity but not quality decreased the expression of the tight
      junction proteins occludin and claudin-1 in the small intestine. These changes
      seemed to result in enhanced portal vein endotoxin concentrations and fatty liver
      disease after feeding diet enriched with saturated and monounsaturated fatty
      acids but not polyunsaturated fatty acids. Neither fatty acid quantity nor
      quality significantly influenced the intestinal serotonergic system. Similarly,
      tryptophan supplementation had no impact on small intestinal barrier or fatty
      liver disease. CONCLUSION: In conclusion, diets rich in saturated or
      monounsaturated fatty acids promote the development of fatty liver disease in
      mice, likely by a dysfunction of the small intestinal mucosal barrier.

PMID- 24321091
TI  - Experiences on recruitment and retention of volunteers in the first HIV vaccine
      trial in Dar es Salam, Tanzania - the phase I/II HIVIS 03 trial.
AB  - BACKGROUND: Eventual control of HIV/AIDS is believed to be ultimately dependent
      on a safe, effective and affordable vaccine. Participation of sub-Saharan Africa
      in the conduct of HIV trials is crucial as this region still experiences high HIV
      incidences. We describe the experience of recruiting and retaining volunteers in
      the first HIV vaccine trial (HIVIS03) in Tanzania. METHODS: In this trial
      enrolled volunteers from amongst Police Officers (POs) in Dar es Salaam were
      primed with HIV-1 DNA vaccine at months 0, 1 and 3; and boosted with HIV-1 MVA
      vaccine at months 9 and 21. A stepwise education provision/sensitization approach
      was employed to eventual recruitment. Having identified a "core" group of POs
      keen on HIV prevention activities, those interested to participate in the vaccine
      trial were invited for a first screening session that comprised of provision of
      detailed study information and medical evaluation. In the second screening
      session results of the initial assessment were provided and those eligible were
      assessed for willingness to participate (WTP). Those willing were consented and
      eventually randomized into the trial having met the eligibility criteria.
      Voluntary participation was emphasized throughout. RESULTS: Out of 408 POs who
      formed the core group, 364 (89.0%) attended the educational sessions. 263 out of
      364 (72.2%) indicated willingness to participate in the HIV vaccine trial. 98% of
      those indicating WTP attended the pre-screening workshops. 220 (85.0%) indicated
      willingness to undergo first screening and 177 POs attended for initial
      screenings, of whom 162 (91.5%) underwent both clinical and laboratory
      screenings. 119 volunteers (73.5%) were eligible for the study. 79 were
      randomized into the trial, while 19 did not turn up, the major reason being
      partner/family advice. 60 volunteers including 15 females were recruited during a
      one-year period. All participated in the planned progress updates workshops.
      Retention into the schedule was: 98% for the 3 DNA/placebo vaccinations, while it
      was 83% and 73% for the first and second MVA/placebo vaccinations respectively.
      CONCLUSION: In this first HIV vaccine trial in Tanzania, we successfully
      recruited the volunteers and there was no significant loss to follow up. Close
      contact and updates on study progress facilitated the observed retention rates.
      TRIAL REGISTRATION NUMBERS: ISRCTN90053831 ISRNCT01132976 and
      ATMR2009040001075080.

PMID- 24321092
TI  - Seasonal changes in the antibody responses against Plasmodium falciparum
      merozoite surface antigens in areas of differing malaria endemicity in Indonesia.
AB  - BACKGROUND: The transmission of malaria in Indonesia is highly heterogeneous
      spatially and seasonally. Anti-malaria antibody responses can help characterize
      this variation. In the present study antibody responses to Plasmodium falciparum
      MSP-1 and AMA-1 were measured to assess the transmission intensity in a hypo
      endemic area of Purworejo and a meso-endemic area of Lampung during low and high
      transmission seasons. METHODS: Filter-paper blood spot samples collected from
      Purworejo and Lampung by cross-sectional survey during high and low transmission
      season were stored at -20 degrees C. Indirect ELISA assays were carried out using
      PfMSP1-19 and PfAMA1 antigens. A positivity threshold was determined by samples
      from local unexposed individuals, and the differences in seroprevalence, antibody
      level and correlation between antibody level and age in each site were
      statistically analysed. RESULTS: Prevalence of antibodies to either PfMSP1-19 or
      PfAMA1 was higher in Lampung than in Purworejo in both the low (51.3 vs 25.0%)
      and high transmission season (53.9 vs 37.5%). The magnitude of antibody responses
      was associated with increasing age in both sites and was higher in Lampung. Age
      adjusted seroconversion rates showed an approximately ten-fold difference between
      Lampung and Purowejo. Two different seroconversion rates were estimated for
      Lampung suggesting behaviour-related differences in exposure. In both settings
      antibody responses to PfMSP1-19 were significantly lower in the low season
      compared to the high season. CONCLUSION: Seasonal changes may be detectable by
      changes in antibody responses. This is particularly apparent in lower
      transmission settings and with less immunogenic antigens (in this case PfMSP1
      19). Examination of antibody levels rather than seroprevalence is likely to be a
      more sensitive indicator of changes in transmission. These data suggest that sero
      epidemiological analysis may have a role in assessing short-term changes in
      exposure especially in low or seasonal transmission settings.

PMID- 24321093
TI  - Bone chips, fibrin glue, and osteogeneration following lateral suboccipital
      craniectomy: a case report.
AB  - BACKGROUND: Suboccipital craniectomy is a conventional approach for exploring
      cerebellopontine angle lesions. A variety of techniques have been successfully
      employed to reconstruct a craniectomy. This is the first report about the
      histological findings after performing a cranioplasty by using a mixture of
      autologous bone chips and human allogenic fibrin glue. CASE PRESENTATION: A 53
      year-old German woman underwent left lateral suboccipital retrosigmoidal
      craniectomy for treatment of trigeminal neuralgia in 2008. Cranioplasty was
      perfomed by using a mixture of autologous bone chips and human allogenic fibrin
      glue. Due to recurrent neuralgia, a second left lateral suboccipital craniectomy
      was performed in 2012. The intraoperative findings revealed a complete
      ossification of the former craniotomy including widely mature trabecular bone
      tissue in the histological examination. CONCLUSION: A mixture of autologous bone
      chips and human allogenic fibrin glue seems to provide sufficient bone
      regeneration revealed by histological and neuroradiological examinations.

PMID- 24321094
TI  - NOTCH1 signaling regulates the BMP2/DLX-3 directed osteogenic differentiation of
      dental follicle cells.
AB  - Dental follicle cells (DFCs) are dental stem/progenitor cells and the genuine
      precursors of alveolar osteoblasts and dental cementoblasts. A previous study
      showed that the transcription factor DLX3 (distal less homeobox 3) supports the
      osteogenic differentiation in DFCs via a positive feedback loop with the bone
      morghogenetic protein (BMP) 2. Until today, however, the control of this
      BMP2/DLX3 pathway by additional signaling pathways remains elusive. Previous
      studies also suggested that the NOTCH signaling pathway plays a role in the
      osteogenic differentiation of DFCs. In this study we showed that DLX3
      overexpression and the initiation of the osteogenic differentiation by BMP2 or
      dexamethasone induced the NOTCH signaling pathway in DFCs. However, the induction
      of NOTCH-signaling impaired not only the osteogenic differentiation (ALP activity
      and mineralized nodules) but also the expression of the transcription factor DLX3
      and the activation of the BMP-signaling pathway. So, NOTCH signaling plays a
      regulatory role for the osteogenic differentiation of DFCs. In conclusion,
      results of our study suggest that the NOTCH-signaling pathway, which is activated
      during the osteogenic differentiation of DFCs, regulates the BMP2/DLX3 directed
      differentiation of DFCs via a negative feed-back loop. 

PMID- 24321095
TI  - Shikonin shortens the circadian period: possible involvement of Top2 inhibition.
AB  - The naphthoquinone pigment, shikonin, is a natural product derived from
      Lithospermum erythrorhizon and an active component of a Chinese traditional
      herbal therapeutic. We identified shikonin as a candidate for shortening the
      circadian period using real-time reporter gene assays based on NIH3T3-derived
      stable reporter cells. Period length that became shortened in cells incubated
      with shikonin or etoposide reverted to that of control cells after continued
      incubation without these compounds. These findings indicated that shikonin and
      etoposide shorten the circadian period reversibly and through similar mechanisms.
      Topoisomerase II (Top2)-specific decatenation assays confirmed that shikonin,
      liker etoposide, is a Top2 inhibitor. Shikonin was incorporated into the nucleus
      and Top2 was located in the Bmal1 promoter, suggesting the relationship between
      Bmal1 transcription and Top2 inhibition. Top2a siRNA also shortened period
      length, suggesting that Top2 is involved in this process. Promoter assays showed
      that Top2a siRNA, etoposide and shikonin reduce Bmal1 promoter activity. These
      findings indicated that Top2 is involved in Bmal1 transcription and influences
      the circadian period, and that shikonin is a novel contributor to the control of
      period length in mammalian cells. 

PMID- 24321096
TI  - SREBP-2 negatively regulates FXR-dependent transcription of FGF19 in human
      intestinal cells.
AB  - Sterol regulatory element-binding protein-2 (SREBP-2) is a basic helix-loop-helix
      leucine zipper transcription factor that positively regulates transcription of
      target genes involved in cholesterol metabolism. In the present study, we have
      investigated a possible involvement of SREBP-2 in human intestinal expression of
      fibroblast growth factor (FGF)19, which is an endocrine hormone involved in the
      regulation of lipid and glucose metabolism. Overexpression of constitutively
      active SREBP-2 decreased FGF19 mRNA levels in human colon-derived LS174T cells.
      In reporter assays, active SREBP-2 overexpression suppressed GW4064/FXR-mediated
      increase in reporter activities in regions containing the IR-1 motif (+848 to
      +5200) in the FGF19 gene. The suppressive effect disappeared in reporter
      activities in the region containing the IR-1 motif when the mutation was
      introduced into the IR-1 motif. In electrophoretic mobility shift assays, binding
      of the FXR/retinoid X receptor alpha heterodimer to the IR-1 motif was attenuated
      by adding active SREBP-2, but SREBP-2 binding to the IR-1 motif was not observed.
      In chromatin immunoprecipitation assays, specific binding of FXR to the IR-1
      containing region of the FGF19 gene (+3214 to +3404) was increased in LS174T
      cells by treatment with cholesterol and 25-hydroxycholesterol. Specific binding
      of SREBP-2 to FXR was observed in glutathione-S-transferase (GST) pull-down
      assays. These results suggest that SREBP-2 negatively regulates the FXR-mediated
      transcriptional activation of the FGF19 gene in human intestinal cells. 

PMID- 24321097
TI  - Luteolin exhibits anti-inflammatory effects by blocking the activity of heat
      shock protein 90 in macrophages.
AB  - Septic diseases represent the prevalent complications in intensive care units.
      Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however,
      the molecular mechanism beneath luteolin mediated immune modulation remains
      unclear. Here in vitro investigations showed that luteolin dose-dependently
      inhibited LPS-triggered secretion and relocation of high mobility group B-1
      (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-alpha) and
      nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that
      luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed
      HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein
      level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun
      and Akt. In vivo investigations showed that luteolin effectively protected mice
      from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study
      suggested that luteolin may act as a potential therapeutic reagent for treating
      septic diseases. 

PMID- 24321098
TI  - The N-terminal strand modulates immunoglobulin light chain fibrillogenesis.
AB  - It has been suggested that the N-terminal strand of the light chain variable
      domain (V(L)) protects the molecule from aggregation by hindering spurious
      intermolecular contacts. We evaluated the impact of mutations in the N-terminal
      strand on the thermodynamic stability and kinetic of fibrillogenesis of the V(L)
      protein 6aJL2. Mutations in this strand destabilized the protein in a position
      dependent manner, accelerating the fibrillogenesis by shortening the lag time; an
      effect that correlated with the extent of destabilization. In contrast, the
      effect on the kinetics of fibril elongation, as assessed in seeding experiments
      was of different nature, as it was not directly dependant on the degree of
      destabilization. This finding suggests different factors drive the nucleation
      dependent and elongation phases of light chain fibrillogenesis. Finally, taking
      advantage of the dependence of the Trp fluorescence upon environment, four single
      Trp substitutions were made in the N-terminal strand, and changes in solvent
      exposure during aggregation were evaluated by acrylamide-quenching. The results
      suggest that the N-terminal strand is buried in the fibrillar state of 6aJL2
      protein. This finding suggest a possible explanation for the modulating effect
      exerted by the mutations in this strand on the aggregation behavior of 6aJL2
      protein.

PMID- 24321100
TI  - Primary cutaneous follicle center lymphoma arising adjacent to silicone breast
      implant.

PMID- 24321101
TI  - Usefulness of magnetic resonance in patients with invasive cancer eligible for
      breast conservation: a comparative study.
AB  - BACKGROUND: The role of magnetic resonance imaging (MRI) in newly detected breast
      cancer remains controversial. We investigated the impact of preoperative MRI on
      surgical management of infiltrating breast carcinoma (IBC). METHODS: We reviewed
      data of 237 patients with IBC who were suitable for breast-conserving surgery
      (BCS) between 2009 and 2011. Of these patients, 109 underwent preoperative MRI
      (46%; MRI group) and 128 did not (54%; no-MRI group). We analyzed MRI-triggered
      changes in surgical plan and compared differences in rates of positive margins
      and mastectomy. RESULTS: Tumor size was larger in the MRI group (16.8 mm vs. 13.9
      mm; P < .001). MRI changed the initial surgical planning in 18 of 109 patients
      (16.5%) because of detection of larger tumor diameter requiring wider resection
      (8 patients [7.3%]) or additional malignant lesions in the ipsilateral (9
      patients [8.2%]) or contralateral breast (1 patient [0.9%]). MRI-triggered
      treatment changes included mastectomy (n = 12), wider excision (n = 5), and
      contralateral BCS (n = 1). Reoperation rates for positive margins after BCS
      appeared higher in the no-MRI group (4.1% vs. 8.6%), but the difference missed
      statistical significance (P = .9). Overall mastectomy rates were higher in the
      MRI group (13.7% vs. 7.0%; P < .05). The likelihood of having a change of
      treatment resulting from MRI was significantly higher for patients with tumors >
      15 mm and for those with positive lymph nodes. CONCLUSION: Lymph node positivity
      and tumor size > 15 mm may predict an MRI-triggered change in surgical plan.
      Preoperative MRI resulted in higher mastectomy rates justified by biopsy-proven
      additional foci of carcinoma and did not significantly reduce reoperation rates
      for positive margins.

PMID- 24321102
TI  - Prospective study of the effect of the 21-gene assay on adjuvant clinical
      decision-making in Japanese women with estrogen receptor-positive, node-negative,
      and node-positive breast cancer.
AB  - BACKGROUND: In this study we investigated if the 21-gene assay result affects
      adjuvant decision-making in Japanese women with ER+ invasive EBC. PATIENTS AND
      METHODS: A total of 124 consecutive eligible patients with ER+, HER2-negative EBC
      and 0 to 3 positive lymph nodes were enrolled. Treatment recommendations,
      physicians' confidence and patients' decisional conflict before and after
      knowledge of the Recurrence Score results of the 21-gene assay were recorded.
      RESULTS: One-hundred four patients (84%) had N0 disease, including
      micrometastases, and 20 (16%) had N+ disease. Overall, recommendations changed in
      33% (95% CI, 24%-43%) of N0 and 65% (95% CI, 41%-85%) of N+ patients. In 27 of 48
      (56%) of N0 and 13 of 15 (87%) of N+ patients an initial recommendation for
      chemohormonal therapy was revised to only hormonal therapy after assay results,
      and in 7 of 56 (13%) of N0 and 0 of 5 N+ patients from only hormonal to combined
      chemohormonal therapy. Decisions appeared to follow the Recurrence Score results
      for low and high values. For patients with intermediate Recurrence Score values,
      overall recommendations for chemohormonal treatment tended to decrease after
      assay results. Physicians' confidence increased in 106 of 124 (85.5%; 95% CI, 78%
      91%) cases. Patients' decisional conflict significantly improved as indicated by
      changes in the total score and the 5 defined subscores (P = .014 for Informed
      Subscore; P < .001 for all others). CONCLUSION: Results from this prospective
      study in a Japanese population confirm an effect of the 21-gene assay results on
      adjuvant treatment decision-making, consistent with reported experiences from the
      United States and Europe.

PMID- 24321103
TI  - Genetic diagnosis and genetic counseling for androgen-insensitivity syndrome: a
      report of three cases.
AB  - AIM: In order to verify androgen-insensitivity syndrome (AIS) for three
      individuals and their mothers, genetic diagnosis was performed after genetic
      counseling. METHODS: Polymerase chain reaction analysis was used for each exon of
      the androgen receptor (AR Xq11-q12) gene. The amplified DNA fragments were
      detected by gel electrophoresis. The DNA fragments were sequenced and their
      sequences were compared with those in a database (The Androgen Receptor Gene
      Mutations Database World Wide Web Server). RESULTS: A missense mutation was
      identified in exon 7 in case 1, deletions of exons 1 and 2 were identified in
      case 2, and a nonsense mutation was identified in the triplet repeat region of
      exon 1 in case 3. The mothers of the patients were also verified to be carriers
      of the mutations. CONCLUSION: Genetic diagnosis is a very useful method for
      diagnosing AIS. However, genetic counseling, including emotional support for the
      mother, is an essential component of genetic diagnosis.

PMID- 24321105
TI  - Study of PKRBD in HCV genotype 3a infected patients in response to interferon
      therapy in Pakistani population.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver cirrhosis and
      hepatocellular carcinoma and infects about 3% world population. Response to
      interferon therapy depends upon the genotype of the virus and factors associated
      with the host. Despite a good response to interferon therapy, a considerable
      number of genotype 3a infected patients remains unalleviated. RESULTS: In total
      forty-nine patients including twenty-five non-responders (non-SVR) and twenty
      four responders (SVR) were recruited. Patients were tested for viral status at
      different intervals and the isolated RNA was sequenced for the NS5A region in
      both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients
      did not confirm any significant difference in the number of mutations. However,
      when the sequence downstream to the PKRBD of NS5A was compared, two important
      statistically significant mutations were observed; at positions 2309 (Ala to Ser)
      and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein
      structure and important structural changes were observed. Statistically
      significant difference was also observed when age groups of patients were
      compared; younger patients showed better response than the older ones.
      CONCLUSIONS: The region between PKRBD and IRRDR may be important for prediction
      of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any
      involvement in treatment response. Further functional analyses of these findings
      can help in understanding the involvement of the NS5A region in interferon
      treatment of HCV-3a infected patients.

PMID- 24321104
TI  - Subchondral bone in osteoarthritis: insight into risk factors and microstructural
      changes.
AB  - Osteoarthritis (OA) is a major cause of disability in the adult population. As a
      progressive degenerative joint disorder, OA is characterized by cartilage damage,
      changes in the subchondral bone, osteophyte formation, muscle weakness, and
      inflammation of the synovium tissue and tendon. Although OA has long been viewed
      as a primary disorder of articular cartilage, subchondral bone is attracting
      increasing attention. It is commonly reported to play a vital role in the
      pathogenesis of OA. Subchondral bone sclerosis, together with progressive
      cartilage degradation, is widely considered as a hallmark of OA. Despite the
      increase in bone volume fraction, subchondral bone is hypomineralized, due to
      abnormal bone remodeling. Some histopathological changes in the subchondral bone
      have also been detected, including microdamage, bone marrow edema-like lesions
      and bone cysts. This review summarizes basic features of the osteochondral
      junction, which comprises subchondral bone and articular cartilage. Importantly,
      we discuss risk factors influencing subchondral bone integrity. We also focus on
      the microarchitectural and histopathological changes of subchondral bone in OA,
      and provide an overview of their potential contribution to the progression of OA.
      A hypothetical model for the pathogenesis of OA is proposed.

PMID- 24321106
TI  - C4a-hydroperoxyflavin formation in N-hydroxylating flavin monooxygenases is
      mediated by the 2'-OH of the nicotinamide ribose of NADP+.
AB  - Flavin-dependent monooxygenases must stabilize a C4a-hydroperoxyflavin
      intermediate to hydroxylate their respective substrates. Formation and decay of
      the C4a-hydroperoxyflavin were monitored under rapid reaction kinetic conditions
      in SidA, an N-hydroxylating monooxygenase involved in siderophore biosynthesis.
      Solvent kinetic isotope effect studies of flavin oxidation indicate that both
      hydrogen peroxide elimination and water elimination occur via abstraction of
      hydrogen from the N5 of the flavin. Kinetic isotope effect and density functional
      theory results are consistent with the transfer of a proton from the 2'-OH of the
      nicotinamide ribose of nicotinamide adenine dinucleotide phosphate (NADP+) to the
      C4a-peroxyflavin to form the C4a-hydroperoxyflavin. This represents a novel role
      for NADP+ in the reaction of flavin-dependent enzymes.

PMID- 24321107
TI  - Bortezomib in multiple myeloma: a practice guideline.
AB  - AIMS: Bortezomib (VelcadeTM, PS-341), a first-in-class proteasome inhibitor, has
      been extensively studied either alone or in combination with other agents for the
      treatment of multiple myeloma. We created a provincial guideline for the use of
      bortezomib, in newly diagnosed individuals (both eligible and ineligible for
      transplant) and in individuals with relapsed or refractory multiple myeloma.
      MATERIALS AND METHODS: A systematic review was conducted searching MEDLINE,
      EMBASE, the Cochrane Library and relevant meeting abstracts. Outcomes of interest
      were survival, disease control, response rate, response duration, quality of life
      and adverse effects. Members of the Cancer Care Ontario Hematology Disease Site
      Group (CCO HDSG), comprising physicians with content expertise, epidemiologists
      and consumers, developed a guideline through a systematic process that involved
      assessment of the best available evidence, consensus interpretation of the
      evidence and a validation process involving practitioners across the province.
      RESULTS: The CCO HDSG recommends the use of bortezomib-based combinations in
      previously untreated patients with multiple myeloma who are candidates for
      autologous stem cell transplantation and in individuals who are ineligible for
      autologous stem cell transplantation. The group further recommends the use of
      bortezomib, alone or in combination, for patients with relapsed/refractory
      disease. The evidence did not establish a subgroup of patients with myeloma that
      should be uniquely targeted for therapy with bortezomib. Qualifying statements by
      the HDSG address alternative dosing options, the management of cytopenias and the
      prevention of toxicities, including herpes zoster reactivation. CONCLUSIONS:
      Bortezomib alone or in combination with other agents can be recommended for both
      previously untreated or relapsed/refractory patients with multiple myeloma.
      Guidelines for monitoring and reducing toxicity are provided.

PMID- 24321108
TI  - Generalized eruptive keratoacanthomas of Grzybowski.
AB  - BACKGROUND: The initial patient with generalized eruptive keratoacanthomas was
      described by Grzybowski in 1950. The condition presents as hundreds to thousands
      of small (1-5 mm), flesh-colored to erythematous papules. OBJECTIVE: To review
      the clinical characteristics and treatments of generalized eruptive
      keratoacanthomas of Grzybowski. MATERIALS AND METHODS: We retrospectively
      reviewed the medical literature using PubMed, searching the terms "eruptive,"
      "generalized," "Grzybowski," "keratoacanthoma," and "multiple." Patient reports
      and previous reviews of the subject were critically assessed and the salient
      features presented to the best of our knowledge. RESULTS: Generalized eruptive
      keratoacanthomas of Grzybowski typically present in the fifth to seventh decades
      of life and display an equal preponderance for both men and women. The
      keratoacanthomas are pruritic and predominately appear in sun-exposed regions,
      such as the face (in which they often demonstrate the sign of Zorro) and the
      upper trunk; the tumors also show a predilection for intertriginous areas.
      Topical, intralesional, and systemic treatment modalities have been used; oral
      retinoids are considered the preferred method of treatment. CONCLUSION:
      Generalized eruptive keratoacanthomas of Grzybowski is a rare form of
      keratoacanthoma and is considered a serious condition because the eruptions are
      diffuse, persistent, and recurrent. Constant pruritus, ectropion, visceral
      neoplasms, and unsatisfactory response to treatment are ominous prognostic
      factors. Successful management of this condition has been observed in patients
      treated with systemic retinoids, such as acitretin.

PMID- 24321109
TI  - Experiences of Kenyan healthcare workers providing services to men who have sex
      with men: qualitative findings from a sensitivity training programme.
AB  - INTRODUCTION: Men who have sex with men (MSM) in Kenya are at high risk for HIV
      and may experience prejudiced treatment in health settings due to stigma. An on
      line computer-facilitated MSM sensitivity programme was conducted to educate
      healthcare workers (HCWs) about the health issues and needs of MSM patients.
      METHODS: Seventy-four HCWs from 49 ART-providing health facilities in the Kenyan
      Coast were recruited through purposive sampling to undergo a two-day MSM
      sensitivity training. We conducted eight focus group discussions (FGDs) with
      programme participants prior to and three months after completing the training
      programme. Discussions aimed to characterize HCWs' challenges in serving MSM
      patients and impacts of programme participation on HCWs' personal attitudes and
      professional capacities. RESULTS: Before participating in the training programme,
      HCWs described secondary stigma, lack of professional education about MSM, and
      personal and social prejudices as barriers to serving MSM clients. After
      completing the programme, HCWs expressed greater acknowledgement of MSM patients
      in their clinics, endorsed the need to treat MSM patients with high professional
      standards and demonstrated sophisticated awareness of the social and behavioural
      risks for HIV among MSM. CONCLUSIONS: Findings provide support for this approach
      to improving health services for MSM patients. Further efforts are needed to
      broaden the reach of this training in other areas, address identified barriers to
      HCW participation and evaluate programme effects on patient and HCW outcomes
      using rigorous methodology.

PMID- 24321110
TI  - HIV among men who have sex with men in Malawi: elucidating HIV prevalence and
      correlates of infection to inform HIV prevention.
AB  - INTRODUCTION: There are limited data characterizing the burden of HIV among men
      who have sex with men (MSM) in Malawi. Epidemiologic research and access to HIV
      prevention, treatment and care services have been traditionally limited in Malawi
      by criminalization and stigmatization of same-sex practices. To inform the
      development of a comprehensive HIV prevention intervention for Malawian MSM, we
      conducted a community-led assessment of HIV prevalence and correlates of
      infection. METHODS: From April 2011 to March 2012, 338 MSM were enrolled in a
      cross-sectional study in Blantyre, Malawi. Participants were recruited by
      respondent-driven sampling methods (RDS), reaching 19 waves. Trained staff
      administered the socio-behavioural survey and HIV and syphilis voluntary
      counselling and testing. RESULTS: Crude HIV and syphilis prevalence estimates
      were 15.4% (RDS-weighted 12.5%, 95% confidence interval (CI): 7.3-17.8) and 5.3%
      (RDS-weighted 4.4%, 95% CI: 3.1-7.6), respectively. Ninety per cent (90.4%,
      unweighted) of HIV infections were reported as being previously undiagnosed.
      Participants were predominantly gay-identified (60.8%) or bisexually identified
      (36.3%); 50.7% reported recent concurrent relationships. Approximately half
      reported consistent condom use (always or almost always) with casual male
      partners, and proportions were relatively uniform across partner types and
      genders. The prevalence of perceived and experienced stigma exceeded 20% for
      almost all variables, 11.4% ever experienced physical violence and 7% were ever
      raped. Current age >25 years (RDS-weighted adjusted odds ratio (AOR) 3.9, 95% CI:
      1.2-12.7), single marital status (RDS-weighted AOR: 0.3; 95% CI: 0.1-0.8) and age
      of first sex with a man <16 years (RDS-weighted AOR: 4.3, 95% CI: 1.2-15.0) were
      independently associated with HIV infection. CONCLUSIONS: Results demonstrate
      that MSM represent an underserved, at-risk population for HIV services in Malawi
      and merit comprehensive HIV prevention services. Results provide a number of
      priorities for research and prevention programmes for MSM, including providing
      access to and encouraging regular confidential HIV testing and counselling, and
      risk reduction counselling related to anal intercourse. Other targets include the
      provision of condoms and compatible lubricants, HIV prevention information, and
      HIV and sexually transmitted infection treatment and adherence support.
      Addressing multiple levels of HIV risk, including structural factors, may help to
      ensure that programmes have sufficient coverage to impact this HIV epidemic among
      MSM.

PMID- 24321111
TI  - Men who have sex with men sensitivity training reduces homoprejudice and
      increases knowledge among Kenyan healthcare providers in coastal Kenya.
AB  - INTRODUCTION: Healthcare workers (HCWs) in Africa typically receive little or no
      training in the healthcare needs of men who have sex with men (MSM), limiting the
      effectiveness and reach of population-based HIV control measures among this
      group. We assessed the effect of a web-based, self-directed sensitivity training
      on MSM for HCWs (www.marps-africa.org), combined with facilitated group
      discussions on knowledge and homophobic attitudes among HCWs in four districts of
      coastal Kenya. METHODS: We trained four district "AIDS coordinators" to provide a
      two-day training to local HCWs working at antiretroviral therapy-providing
      facilities in coastal Kenya. Self-directed learning supported by group
      discussions focused on MSM sexual risk practices, HIV prevention and healthcare
      needs. Knowledge was assessed prior to training, immediately after training and
      three months after training. The Homophobia Scale assessed homophobic attitudes
      and was measured before and three months after training. RESULTS: Seventy-four
      HCWs (68% female; 74% clinical officers or nurses; 84% working in government
      facilities) from 49 health facilities were trained, of whom 71 (96%) completed
      all measures. At baseline, few HCWs reported any prior training on MSM anal
      sexual practices, and most HCWs had limited knowledge of MSM sexual health needs.
      Homophobic attitudes were most pronounced among HCWs who were male, under 30
      years of age, and working in clinical roles or government facilities. Three
      months after training, more HCWs had adequate knowledge compared to baseline (49%
      vs. 13%, McNemar's test p<0.001); this was most pronounced in those with clinical
      or administrative roles and in those from governmental health providers. Compared
      to baseline, homophobic attitudes had decreased significantly three months after
      training, particularly among HCWs with high homophobia scores at baseline, and
      there was some evidence of correlation between improvements in knowledge and
      reduction in homophobic sentiment. CONCLUSIONS: Scaling up MSM sensitivity
      training for African HCWs is likely to be a timely, effective and practical means
      to improve relevant sexual health knowledge and reduce personal homophobic
      sentiment among HCWs involved in HIV prevention, testing and care in sub-Saharan
      Africa.

PMID- 24321112
TI  - "They are human beings, they are Swazi": intersecting stigmas and the positive
      health, dignity and prevention needs of HIV-positive men who have sex with men in
      Swaziland.
AB  - INTRODUCTION: Despite the knowledge that men who have sex with men (MSM) are more
      likely to be infected with HIV across settings, there has been little
      investigation of the experiences of MSM who are living with HIV in sub-Saharan
      Africa. Using the framework of positive health, dignity and prevention, we
      explored the experiences and HIV prevention, care and treatment needs of MSM who
      are living with HIV in Swaziland. METHODS: We conducted 40 in-depth interviews
      with 20 HIV-positive MSM, 16 interviews with key informants and three focus
      groups with MSM community members. Qualitative analysis was iterative and
      included debriefing sessions with a study staff, a stakeholders' workshop and
      coding for key themes using Atlas.ti. RESULTS: The predominant theme was the
      significant and multiple forms of stigma and discrimination faced by MSM living
      with HIV in this setting due to both their sexual identity and HIV status. Dual
      stigma led to selective disclosure or lack of disclosure of both identities, and
      consequently a lack of social support for care-seeking and medication adherence.
      Perceived and experienced stigma from healthcare settings, particularly around
      sexual identity, also led to delayed care-seeking, travel to more distant clinics
      and missed opportunities for appropriate services. Participants described
      experiences of violence and lack of police protection as well as mental health
      challenges. Key informants, however, reflected on their duty to provide non
      discriminatory services to all Swazis regardless of personal beliefs.
      CONCLUSIONS: Intersectionality provides a framework for understanding the
      experiences of dual stigma and discrimination faced by MSM living with HIV in
      Swaziland and highlights how programmes and policies should consider the specific
      needs of this population when designing HIV prevention, care and treatment
      services. In Swaziland, the health sector should consider providing specialized
      training for healthcare providers, distributing condoms and lubricants and
      engaging MSM as peer outreach workers or expert clients. Interventions to reduce
      stigma, discrimination and violence against MSM and people living with HIV are
      also needed for both healthcare workers and the general population. Finally,
      research on experiences and needs of MSM living with HIV globally can help inform
      comprehensive HIV services for this population.

PMID- 24321114
TI  - HIV prevalence and factors associated with HIV infection among men who have sex
      with men in Cameroon.
AB  - INTRODUCTION: Despite men who have sex with men (MSM) being a key population for
      HIV programming globally, HIV epidemiologic data on MSM in Central Africa are
      sparse. We measured HIV and syphilis prevalence and the factors associated with
      HIV infection among MSM in Cameroon. METHODS: Two hundred and seventy-two and 239
      MSM aged >= 18 from Douala and Yaounde, respectively, were recruited using
      respondent-driven sampling (RDS) for this cross-sectional surveillance study in
      2011. Participants completed a structured questionnaire and HIV and syphilis
      testing. Statistical analyses, including RDS-weighted proportions, bootstrapped
      confidence intervals and logistic regressions, were used. RESULTS: Crude and RDS
      weighted HIV prevalence were 28.6% (73/255) and 25.5% (95% CI 19.1-31.9) in
      Douala, and 47.3% (98/207) and 44.4% (95% CI 35.7-53.2) in Yaounde. Active
      syphilis prevalence in total was 0.4% (2/511). Overall, median age was 24 years,
      62% (317/511) of MSM identified as bisexual and 28.6% (144/511) identified as
      gay. Inconsistent condom use with regular male partners (64.1%; 273/426) and
      casual male and female partners (48.5%; 195/402) was common, as was the
      inconsistent use of condom-compatible lubricants (CCLs) (26.3%; 124/472). In
      Douala, preferring a receptive sexual role was associated with prevalent HIV
      infection [adjusted odds ratio (aOR) 2.33, 95% CI 1.02-5.32]. Compared to MSM
      without HIV infection, MSM living with HIV were more likely to have ever accessed
      a health service targeting MSM in Douala (aOR 4.88, 95% CI 1.63-14.63). In
      Yaounde, MSM living with HIV were more likely to use CCLs (aOR 2.44, 95% CI 1.19
      4.97). CONCLUSIONS: High HIV prevalence were observed and condoms and CCLs were
      used inconsistently indicating that MSM are a priority population for HIV
      prevention, treatment and care services in Douala and Yaounde. Building the
      capacity of MSM community organizations and improving the delivery and scale-up
      of multimodal interventions for MSM that are sensitive to concerns about
      confidentiality and the complex individual, social, community-level and policy
      challenges are needed to successfully engage young MSM in the continuum of HIV
      care. In addition to scaling up condom and CCL access, evaluating the feasibility
      of novel biomedical interventions, including antiretroviral pre-exposure
      prophylaxis and early antiretroviral therapy for MSM living with HIV in Cameroon,
      is also warranted.

PMID- 24321113
TI  - Epidemiology of HIV among female sex workers, their clients, men who have sex
      with men and people who inject drugs in West and Central Africa.
AB  - INTRODUCTION: The West and Central Africa (WCA) sub-region is the most populous
      region of sub-Saharan Africa (SSA), with an estimated population of 356 million
      living in 24 countries. The HIV epidemic in WCA appears to have distinct dynamics
      compared to the rest of SSA, being more concentrated among key populations such
      as female sex workers (FSWs), men who have sex with men (MSM), people who inject
      drugs (PWID) and clients of FSWs. To explore the epidemiology of HIV in the
      region, a systematic review of HIV literature among key populations in WCA was
      conducted since the onset of the HIV epidemic. METHODS: We searched the databases
      PubMed, CINAHL and others for peer-reviewed articles regarding FSWs, MSM and PWID
      in 24 countries with no date restriction. Inclusion criteria were sensitive and
      focused on inclusion of any HIV prevalence data among key populations. HIV
      prevalence was pooled, and in each country key themes were extracted from the
      literature. RESULTS: The search generated 885 titles, 214 abstracts and 122 full
      articles, of which 76 met inclusion and exclusion criteria providing HIV
      prevalence data. There were 60 articles characterizing the burden of disease
      among FSWs, eight for their clients, one for both, six for MSM and one for PWID.
      The pooled HIV prevalence among FSWs was 34.9% (n=14,388/41,270), among their
      clients was 7.3% (n=435/5986), among MSM was 17.7% (n=656/3714) and among PWID
      from one study in Nigeria was 3.8% (n=56/1459). CONCLUSIONS: The disproportionate
      burden of HIV among FSWs appears to be consistent from the beginning of the HIV
      epidemic in WCA. While there are less data for other key populations such as
      clients of FSWs and MSM, the prevalence of HIV is higher among these men compared
      to other men in the region. There have been sporadic reports among PWID, but
      limited research on the burden of HIV among these men and women. These data
      affirm that the HIV epidemic in WCA appears to be far more concentrated among key
      populations than the epidemics in Southern and Eastern Africa. Evidence-based HIV
      prevention, treatment and care programmes in WCA should focus on engaging
      populations with the greatest burden of disease in the continuum of HIV care.

PMID- 24321115
TI  - A pilot cohort study to assess the feasibility of HIV prevention science research
      among men who have sex with men in Dakar, Senegal.
AB  - INTRODUCTION: Men who have sex with men (MSM) are disproportionately burdened by
      HIV in Senegal, across sub-Saharan Africa and throughout the world. This is
      driven in part by stigma, and limits health achievements and social capital among
      these populations. To date, there is a limited understanding of the feasibility
      of prospective HIV prevention studies among MSM in Senegal, including HIV
      incidence and cohort retention rates. METHODS: One hundred and nineteen men who
      reported having anal sex with another man in the past 12 months were randomly
      selected from a sampling frame of 450 unique members of community groups serving
      MSM in Dakar. These men were enrolled in a 15-month pilot cohort study
      implemented by a community-based partner. The study included a structured survey
      instrument and biological testing for HIV, syphilis and hepatitis B virus at two
      time points. RESULTS: Baseline HIV prevalence was 36.0% (43/114), with cumulative
      HIV prevalence at study end being 47.2% (51/108). The annualized incidence rate
      was 16% (8/40 at risk for seroconversion over 15 months of follow-up, 95%
      confidence interval 4.6-27.4%). Thirty-seven men were lost to follow up,
      including at least four deaths. Men who were able to confide in someone about
      health, emotional distress and sex were less likely to be HIV positive (OR 0.36,
      p < 0.05, 95% CI 0.13, 0.97). CONCLUSIONS: High HIV prevalence and incidence, as
      well as mortality in this young population of Senegalese MSM indicate a public
      health emergency. Moreover, given the high burden of HIV and rate of incident HIV
      infections, this population appears to be appropriate for the evaluation of novel
      HIV prevention, treatment and care approaches. Using a study implemented by
      community-based organizations, there appears to be feasibility in implementing
      interventions addressing the multiple levels of HIV risk among MSM in this
      setting. However, low retention across arms of this pilot intervention, and in
      the cohort, will need to be addressed for larger-scale efficacy trials to be
      feasible.

PMID- 24321116
TI  - Outcomes of a community-based HIV-prevention pilot programme for township men who
      have sex with men in Cape Town, South Africa.
AB  - INTRODUCTION: Men who have sex with men (MSM) in Cape Town's townships remain in
      need of targeted HIV-prevention services. In 2012, a pilot community-based HIV
      prevention programme was implemented that aimed to reach MSM in five Cape Town
      townships, disseminate HIV-prevention information and supplies, and promote the
      use of condoms and HIV services. METHODS: Convenience sampling was used to
      recruit self-identified MSM who were 18 years old or older in five Cape Town
      townships. The six-month pilot programme trained five community leaders who,
      along with staff, provided HIV-prevention information and supplies to MSM through
      small-group meetings, community-based social activities and inter-community
      events. After the completion of the pilot programme, in-depth interviews and
      focus group discussions (FGDs) were conducted with a subset of conveniently
      sampled participants and with each of the community leaders. Qualitative data
      were then analyzed thematically. RESULTS: Overall, 98 mostly gay-identified black
      MSM consented to participate, 57 community-based activities were facilitated and
      9 inter-community events were conducted. Following their enrollment, 60% (59/98)
      of participants attended at least one pilot activity. Of those participants, 47%
      (28/59) attended at least half of the scheduled activities. A total of 36
      participants took part in FGDs, and five in-depth interviews were completed with
      community leaders. Participants reported gaining access to MSM-specific HIV
      prevention information, condoms and water-based lubricant through the small-group
      meetings. Some participants described how their feelings of loneliness, social
      isolation, self-esteem and self-efficacy were improved after taking part.
      CONCLUSIONS: The social activities and group meetings were viable strategies for
      disseminating HIV-prevention information, condoms and water-based lubricant to
      MSM in this setting. Many MSM were also able to receive social support, reduce
      social isolation and improve their self-esteem. Further research is needed to
      explore factors affecting attendance and the sustainability of these activities.
      Perspectives of MSM who did not attend pilot activities regularly were not
      equally represented in the final qualitative interviews, which could bias the
      findings. The use of community-based activities and small-group meetings should
      be explored further as components to ongoing HIV-prevention interventions for MSM
      in this setting.

PMID- 24321117
TI  - A cross-sectional assessment of the burden of HIV and associated individual- and
      structural-level characteristics among men who have sex with men in Swaziland.
AB  - INTRODUCTION: Similar to other Southern African countries, Swaziland has been
      severely affected by HIV, with over a quarter of its reproductive-age adults
      estimated to be living with the virus, equating to an estimate of 170,000 people
      living with HIV. The last several years have witnessed an increase in the
      understanding of the potential vulnerabilities among men who have sex with men
      (MSM) in neighbouring countries with similarly widespread HIV epidemics. To date,
      there are no data characterizing the burden of HIV and the HIV prevention,
      treatment and care needs of MSM in Swaziland. METHODS: In 2011, 324 men who
      reported sex with another man in the last 12 months were accrued using respondent
      driven sampling (RDS). Participants completed HIV testing using Swazi national
      guidelines as well as structured survey instruments administered by trained
      staff, including modules on demographics, individual-level behavioural and
      biological risk factors, social and structural characteristics and uptake of HIV
      services. Population and individual weights were computed separately for each
      variable with a data-smoothing algorithm. The weights were used to estimate RDS
      adjusted univariate estimates with 95% bootstrapped confidence intervals (BCIs).
      Crude and RDS-adjusted bivariate and multivariate analyses were completed with
      HIV as the dependent variable. RESULTS: Overall, HIV prevalence was 17.6%
      (n=50/284), although it was strongly correlated with age in bivariate- [odds
      ratio (OR) 1.2, 95% BCI 1.15-1.21] and multivariate-adjusted analyses (adjusted
      OR 1.24, 95% BCI 1.14-1.35) for each additional year of age. Nearly, 70.8%
      (n=34/48) were unaware of their status of living with HIV. Condom use with all
      sexual partners and condom-compatible-lubricant use with men were reported by
      1.3% (95% CI 0.0-9.7). CONCLUSIONS: Although the epidemic in Swaziland is driven
      by high-risk heterosexual transmission, the burden of HIV and the HIV prevention,
      treatment and care needs of MSM have been understudied. The data presented here
      suggest that these men have specific HIV acquisition and transmission risks that
      differ from those of other reproductive-age adults. The scale-up in HIV services
      over the past decade has likely had limited benefit for MSM, potentially
      resulting in a scenario where epidemics of HIV among MSM expand in the context of
      slowing epidemics in the general population, a reality observed in most of the
      world.

PMID- 24321118
TI  - Building the evidence base for urgent action: HIV epidemiology and innovative
      programming for men who have sex with men in sub-Saharan Africa.
AB  - While still an understudied area, there is a growing body of studies highlighting
      epidemiologic data on men who have sex with men (MSM) in sub-Saharan Africa (SSA)
      which challenge the attitudes of complacency and irrelevancy among donors and
      country governments that are uncomfortable in addressing key populations (KPs).
      While some of the past inaction may be explained by ignorance, new data document
      highly elevated and sustained HIV prevalence that is seemingly isolated from
      recent overall declines in prevalence. The articles in this series highlight new
      studies which focus on the stark epidemiologic burden in countries from
      concentrated, mixed and generalized epidemic settings. The issue includes
      research from West, Central, East and Southern Africa and explores the pervasive
      impact of stigma and discrimination as critical barriers to confronting the HIV
      epidemic among MSM and the intersecting stigma and marginalization found between
      living with HIV and sexual minority status. Interventions to remove barriers to
      service access, including those aimed at training providers and mobilizing
      communities even within stigmatized peri-urban settings, are featured in this
      issue, which further demonstrates the immediate need for comprehensive action to
      address HIV among MSM in all countries in the region, regardless of epidemic
      classification. 

PMID- 24321120
TI  - Mutational analysis of Plasmodium falciparum dihydrofolate reductase and
      dihydropteroate synthase genes in the interior division of Sabah, Malaysia.
AB  - BACKGROUND: The sulphadoxine/pyrimethamine (SDX/PYR) combination had been chosen
      to treat uncomplicated falciparum malaria in Malaysia for more than 30 years. Non
      silent mutations in dihydrofolate reductase (dhfr) and dihydropteroate synthase
      (dhps) genes are responsible for the resistance to pyrimethamine and
      sulphadoxine, respectively. This study reports the mutational analysis of pfdhfr
      and pfdhps in single Plasmodium falciparum infection isolates from the interior
      division of Sabah, Malaysian Borneo. METHODS: A total of 22 P. falciparum single
      infection isolates collected from two districts of the interior division of Sabah
      from February to November 2010 were recruited for the mutational study of pfdhfr
      and pfdhps. Both genes were amplified by nested PCR prior to DNA sequencing and
      mutational analysis. RESULTS: A total of three pfdhfr and four pfdhps alleles
      were identified. The most prevalent pfdhfr allele is ANRNL (86%) involving triple
      mutation at position 108(S to N), 59(C to R) and 164(I to L). In pfdhps, two
      novel alleles, SGTGA (73%) and AAKAA (5%) were identified. Alleles involving
      triple mutation in both pfdhfr (ANRNL) and pfdhps (SGTGA), which were absent in
      Sabah in a study conducted about 15 years ago, are now prevalent. CONCLUSIONS:
      High prevalence of mutations in SDX/PYR associated drug resistance genes are
      reported in this study. This mutational study of pfdhps and pfdhfr indicating
      that SDX/PYR should be discontinued in this region.

PMID- 24321121
TI  - Parenteral organophosphorus poisoning in a rural emergency department: a case
      report.
AB  - BACKGROUND: Poisoning is a common presentation in the emergency department. Oral
      exposures to organophosphorus compounds are especially frequent in rural and
      agricultural regions of South Asia and throughout the developing world. CASE
      PRESENTATION: Here we report a case of deliberate self-harm with an
      organophosphorus pesticide via the relatively uncommon parenteral route. A young
      woman injected herself with chlorpyriphos. Although the cholinergic effects were
      mild, cellulitis and abscess development were noted as a result. CONCLUSION:
      Resource limited agricultural countries like Nepal present health care workers
      with numerous challenges in poisoning management. This case represents a rare but
      potentially morbid method of agrochemical poison exposure.

PMID- 24321122
TI  - Protein engineering.

PMID- 24321123
TI  - Features and treatment modality of iliopsoas abscess and its outcome: a 6-year
      hospital-based study.
AB  - BACKGROUND: Percutaneous drainage (PCD) and surgical intervention are two primary
      treatment options for iliopsoas abscess (IPA). However, there is currently no
      consensus on when to use PCD or surgical intervention, especially in patients
      with gas-forming IPA. This study compared the characteristics of patients with
      gas-forming and non-gas forming IPA and their mortality rates under different
      treatment modalities. An algorithm for selecting appropriate treatment for IPA
      patients is proposed based on our findings. METHODS: Eighty-eight IPA patients
      between July 2007 and February 2013 were enrolled in this retrospective study.
      Patients < 18 years of age or with an incomplete course of treatment were
      excluded. Demographic information, clinical characteristics, and outcomes of
      different treatment approaches were compared between gas-forming IPA and non-gas
      forming IPA patients. RESULTS: Among the 88 enrolled patients, 27 (31%) had gas
      forming IPA and 61 (69%) had non-gas forming IPA. The overall intra-hospital
      mortality rate was 25%. The gas-forming IPA group had a higher intra-hospital
      mortality rate (12/27, 44.0%) than the non-gas forming IPA group (10/61, 16.4%)
      (P < 0.001). Only 2 of the 13 patients in the gas-forming IPA group initially
      accepting PCD had a good outcome (success rate = 15.4%). Three of the 11 IPA
      patients with failed initial PCD expired, and 8 of the 11 patients with failed
      initial PCD accepted salvage operation, of whom 5 survived. Seven of the 8 gas
      forming IPA patients accepting primary surgical intervention survived (success
      rate = 87.5%). Only 1 of the 6 gas-forming IPA patients who accepted antibiotics
      alone, without PCD or surgical intervention, survived (success rate = 16.7%). In
      the non-gas forming IPA group, 23 of 61 patients initially accepted PCD, which
      was successful in 17 patients (73.9%). The success rate of PCD was much higher in
      the non-gas forming group than in the gas-forming group (P <0.01). CONCLUSIONS:
      Based on the high failure rate of PCD and the high success rate of surgical
      intervention in our samples, we recommend early surgical intervention with
      appropriate antibiotic treatment for the patients with gas-forming IPA. Either
      PCD or primary surgical intervention is a suitable treatment for patients with
      non-gas forming IPA.

PMID- 24321124
TI  - Molecular modeling and analysis of hepatitis E virus (HEV) papain-like cysteine
      protease.
AB  - The biochemical or biophysical characterization of a papain-like cysteine
      protease in HEV ORF1-encoded polyprotein still remains elusive. Very recently, we
      have demonstrated the indispensability of ORF1 protease-domain cysteines and
      histidines in HEV replication, ex vivo (Parvez, 2013). In this report, the
      polyprotein partial sequences of HEV strains and genetically-related RNA viruses
      were analyzed, in silico. Employing the consensus-prediction results of RUBV
      p(150) protease as structural-template, a 3D model of HEV-protease was deduced.
      Similar to RUBV-p(150), a 'papain-like beta-barrel fold' structurally confirmed
      the classification of HEV-protease. Further, we recognized a catalytic 'Cys434
      His443' dyad homologue of RUBV-p(150) (Cys1152-His1273) and FMDV-L(pro) (Cys51
      His148) in line with our previous mutational analysis that showed essentiality of
      'His443' but not 'His590' in HEV viability. Moreover, a RUBV 'Zn(2+) binding
      motif' (Cys1167-Cys1175-Cys1178-Cys1225-Cys1227) equivalent of HEV was identified
      as 'Cys457-His458-Cys459 and Cys481-Cys483' residues within the 'beta-barrel
      fold'. Notably, unlike RUBV, 'His458' also clustered therein, that was in
      conformity with the consensus cysteine protease 'Zn(2+)-binding motif'. By
      homology, we also proposed an overlapping 'Ca(2+)-binding site' 'D-X-[DNS]
      [ILVFYW]-[DEN]-G-[GP]-XX-DE' signature, and a 'proline-rich motif' interacting
      'tryptophan (W437-W472)' module in the modeled structure. Our analysis of the
      predicted model therefore, warrants critical roles of the 'catalytic dyad' and
      'divalent metal-binding motifs' in HEV protease structural-integrity, ORF1 self
      processing, and RNA replication. This however, needs further experimental
      validations. 

PMID- 24321125
TI  - Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel
      pancreatic lipase inhibitor.
AB  - BACKGROUND: There is completely no report about both hen egg anti-lipase
      immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate
      and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover,
      we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase
      activity in vitro, and examined its ability to prevent obesity in a murine high
      fat diet-induced obesity model. METHODS: We determined the inhibitory action of
      Anti-lipase IgY on lipase activity in vitro. We also focused our evaluation on
      the anti-obesity properties of Anti-lipase IgY in a murine high fat diet-induced
      obesity model. RESULTS: Anti-lipase IgY blocked porcine lipase activity with an
      IC50 of 0.49 MUM. Supplementing the high fat diet with only 0.2% (w/w) of Anti
      lipase IgY for 35 days significantly decreased the weights of intraperitoneal
      adipose tissues, epididymal, mesenteric, retroperitoneal and perirenal adipose
      tissues, and the amounts of hepatic total lipid, triglyceride, and cholesterol.
      This was accompanied by a significant increase in the fecal excretion of
      triglyceride in the absence of diarrhea. Furthermore, Anti-lipase IgY treatment
      restored body weight gain to levels similar to mice fed with Control IgY.
      CONCLUSIONS: This study provides the first report of the development of anti
      lipase IgY and the direct evidence that inhibition of pancreatic lipase using
      Anti-lipase IgY is an effective anti-obesity treatment due to the associated
      increase in fecal excretion of triglyceride.

PMID- 24321126
TI  - Alterations in coxsackievirus and adenovirus receptor confer susceptibility to
      ventricular arrhythmia with an ischemic event.

PMID- 24321127
TI  - Progranulin antibodies entertain a proinflammatory environment in a subgroup of
      patients with psoriatic arthritis.
AB  - INTRODUCTION: Psoriatic arthritis (PsA) is a distinctive inflammatory arthritis
      which may typically develop in a subgroup of individuals suffering from
      psoriasis. We recently described progranulin autoantibodies (PGRN-Abs) in the
      sera of patients with different autoimmune diseases including seronegative
      polyarthritis. In the present study we investigated the occurrence of PGRN-Abs in
      PsA. METHODS: PGRN-Abs were determined in 260 patients with PsA, 100 patients
      with psoriasis without arthritic manifestations (PsC) and 97 healthy controls
      using a recently described ELISA. PGRN plasma levels were determined from
      subgroups by a commercially available ELISA-kit. Possible functional effects of
      PGRN-antibodies were analysed in vitro by tumour necrosis factor (TNF)-alpha
      mediated cytotoxicity assays using WEHI-S and HT1080 cells. RESULTS: PGRN-Abs
      were detected with relevant titres in 50/260 (19.23%) patients with PsA, but in
      0/100 patients with psoriasis without arthritic manifestations (P = 0.0001). All
      PGRN-Abs belonged to immunoglobulin G (IgG). PGRN-Abs were significantly more
      frequent in PsA patients with enthesitis or dactylitis. PGRN-Abs were also more
      frequent in PsA patients receiving treatment with TNF-alpha-blockers than in
      patients treated without TNF-alpha-blockers (20.8% versus 17.4%; P = 0.016). PGRN
      plasma levels were significantly lower in PGRN-Ab-positive patients with PsA than
      in healthy controls and patients with psoriasis without arthritic manifestations
      (P < 0.001), indicating a neutralizing effect of PGRN-Abs. Moreover cytotoxicity
      assays comparing PGRN-antibody positive with negative sera from matched patients
      with PsA, clearly showed a proinflammatory effect of PGRN antibodies. CONCLUSION:
      Neutralizing PGRN-Abs occur with relevant titres in a subgroup of patients with
      PsA, but not in patients without arthritic manifestations (PsC). PGRN-Ab-positive
      patients had more frequent enthesitis or dactylitis. TNF-alpha-induced
      cytotoxicity assays demonstrated that the protective effects of progranulin were
      inhibited by serum containing PGRN-Abs. This suggests that PGRN-Ab might not only
      be useful as a diagnostic and prognostic marker, but may provide a
      proinflammatory environment in a subgroup of patients with PsA.

PMID- 24321128
TI  - Sesamoid ossicle of the nuchal ligament.

PMID- 24321130
TI  - Clinical and radiological results 6 years after treatment of traumatic
      thoracolumbar burst fractures with pedicle screw instrumentation and balloon
      assisted endplate reduction.
AB  - BACKGROUND CONTEXT: When used to fixate traumatic thoracolumbar burst fractures,
      pedicle screw constructs may fail in the presence of severe vertebral body
      comminution as the intervertebral disc can creep through the fractured endplates
      leading to insufficient anterior column support. Balloon-assisted endplate
      reduction (BAER) and subsequent calcium phosphate cement augmentation may prevent
      this event by restoring the disc space boundaries. The results of the first
      studies using BAER after pedicle screw fixation are encouraging, showing good
      fracture reduction, few complications, and minimal loss of correction at 2 years
      of follow-up. PURPOSE: To present the clinical and radiological outcome of 20
      patients treated for traumatic thoracolumbar burst fractures with pedicle screws
      and BAER after a minimum of 6 years follow-up. STUDY DESIGN: Prospective trial.
      PATIENT SAMPLE: Twenty consecutive neurologically intact adult patients with
      traumatic thoracolumbar burst fractures were included. OUTCOME MEASURES:
      Radiological parameters (wedge/Cobb angle on plain radiographs and mid-sagittal
      anterior/central vertebral body height on magnetic resonance imaging scans) and
      patient reported parameters (EQ-5D and Oswestry Disability Index) were used.
      METHODS: All patients had previously undergone pedicle screw fixation and BAER
      with calcium phosphate cement augmentation. The posterior instrumentation was
      removed approximately 1.5 years after index surgery. Radiographs were obtained
      preoperatively, postoperatively, after removal of the pedicle screws, and at
      final follow-up (minimum 6 years post-trauma). Magnetic resonance imaging scans
      were obtained preoperatively, 1 month after index surgery, and 1 month after
      pedicle screw removal. Health questionnaires were filled out during the last
      outpatient visit. RESULTS: The pedicle screw instrumentation was removed
      uneventfully in all patients and posterolateral fusion was observed in every
      case. The mean wedge and Cobb angle converged to almost identical values (5.3
      degrees  and 5.8 degrees , respectively) and the mid-sagittal anterior and
      central endplates were reduced to approximately 90% and 80% of the estimated
      preinjury vertebral body height, respectively; this reduction was sustained at
      follow-up. Patient-reported outcomes showed favorable results in 79% of the
      patients. One patient required (posterior) reoperation due to adjacent
      osteoporotic vertebral body collapse after pedicle screw removal. CONCLUSIONS:
      Balloon-assisted endplate reduction is a safe and low-demanding adjunct to
      pedicle screw fixation for the treatment of traumatic thoracolumbar burst
      fractures. It may help achieve minimal residual deformity and reduce the number
      of secondary (anterior) procedures. Despite these positive findings, one in five
      patients experienced daily discomfort and disability.

PMID- 24321129
TI  - Complications, revision fusions, readmissions, and utilization over a 1-year
      period after bone morphogenetic protein use during primary cervical spine
      fusions.
AB  - BACKGROUND CONTEXT: Nationwide estimates examining bone morphogenetic protein
      (BMP) use with cervical spine fusions have been limited to perioperative
      outcomes. PURPOSE: To determine the 1-year risk of complications, cervical
      revision fusions, hospital readmissions, and health care services utilization.
      STUDY DESIGN: A retrospective cohort study from 2002 to 2009 using a nationwide
      claims database. PATIENT SAMPLE: There were 61,937 primary cervical spine fusions
      of which 1,677 received BMP. OUTCOME MEASURES: Complications, revision fusions,
      30-day hospital readmission, and health care utilization. METHODS: Data for these
      analyses come from the Thomson Reuters MarketScan Commercial Claims and
      Encounters Database 2010. Patients were aged 18 to 64 years, receiving and not
      receiving BMP with a primary (C2-C7) cervical spine fusion. All outcomes were
      defined by International Classification of Diseases, 9th edition Clinical
      Modification and Current Procedural and Terminology, 4th edition codes.
      Complications were analyzed as any complication and stratified by nervous system,
      wound, and dysphagia or hoarseness. Cervical revision fusions were determined in
      the 1-year follow-up. Hospital readmission discharge records defined 30-day
      hospital readmission and reason for the readmission. The utilization of at least
      one health care service of cervical spine imaging, epidural usage or
      rehabilitation service was examined. Poisson regression models were used to
      estimate the relative risk and 95% confidence interval (CI). Linear regression
      was used to determine the time to hospital readmission. Results were stratified
      by anterior or posterior and circumferential approaches. RESULTS: Patients
      receiving BMP were 29% more likely to have a complication (adjusted relative risk
      [aRR]=1.29 [95% CI, 1.14-1.46]) and a nervous system complication (aRR=1.42 [95%
      CI, 1.10-1.83]). Cervical revision fusions were more likely among patients
      receiving BMP (aRR=1.69 [95% CI, 1.35-2.13]). The risk of 30-day readmission was
      greater with BMP use (aRR=1.37 [95% CI, 1.07-1.73]) and readmission occurred
      27.4% sooner on an average. Patients receiving BMP were more likely to receive
      computed tomography scans (aRR=1.34 [95% CI, 1.06-1.70]) and epidurals with
      anterior surgical approaches (aRR=1.29 [95% CI, 1.00-1.65]). CONCLUSIONS: These
      findings question both the safety and effectiveness of off-label BMP use in
      primary cervical spine fusions.

PMID- 24321131
TI  - The development of a dynamic, six-axis spine simulator.
AB  - BACKGROUND CONTEXT: Although a great deal of research has been completed to
      characterize the stiffness of spinal specimens, there remains a limited
      understanding of the spine in 6 df and there is a lack of data from dynamic
      testing in six axes. PURPOSE: This study details the development and validation
      of a dynamic six-axis spine simulator. STUDY DESIGN: Biomechanical study.
      METHODS: A synthetic spinal specimen was used for the purpose of tuning the
      simulator, completing positional accuracy tests, and measuring frequency response
      under physiological conditions. The spine simulator was used to complete
      stiffness matrix tests of an L3-L4 lumbar porcine functional spinal unit. Five
      testing frequencies were used, ranging from quasistatic (0.00575 Hz) to dynamic
      (0.5 Hz). Tests were performed without an axial preload and with an axial preload
      of 500 N. RESULTS: The validation tests demonstrated that the simulator is
      capable of producing accurate positioning under loading at frequencies up to 0.5
      Hz using both sine and triangle waveforms. The porcine stiffness matrix tests
      demonstrated that the stiffness matrix is not symmetrical about the principal
      stiffness diagonal. It was also shown that while an increase in test frequency
      generally increased the principal stiffness terms, axial preload had a much
      greater effect. CONCLUSIONS: The spine simulator is capable of characterizing the
      dynamic biomechanics of the spine in six axes and provides a means to better
      understand the complex behavior of the spine under physiological conditions.

PMID- 24321132
TI  - A systematic review of the literature on family functioning across all eating
      disorder diagnoses in comparison to control families.
AB  - The objectives of this review were to systematically identify and evaluate
      quantitative research comparing family functioning (a) in eating disorder
      families with control families, (b) in families with different eating disorder
      diagnoses (c) perceptions of different family members and (d) the relationship
      between family functioning and recovery. This adds to the findings of previous
      reviews of family functioning by including data from control families, the range
      of diagnoses, and focusing on recovery. Findings were considered in relation to
      models of family functioning. Using specific search criteria, 17 research papers
      were identified and evaluated. Findings indicated that eating disorder families
      reported worse family functioning than control families but there was little
      evidence for a typical pattern of family dysfunction. A consistent pattern of
      family dysfunction for different diagnoses was not suggested but patients
      consistently rated their family as more dysfunctional than one or both of their
      parents. With respect to outcome and recovery, those with more positive
      perceptions of family functioning generally had more positive outcomes,
      irrespective of severity of eating disorder. Conclusions were limited by
      inconsistent findings and methodological issues. Further research is needed into
      the relationship between family functioning and outcome and the assessment of
      family functioning beyond self-report. 

PMID- 24321133
TI  - Epidemiology and awareness of hypertension in a rural Ugandan community: a cross
      sectional study.
AB  - BACKGROUND: Hypertension is one of the largest causes of preventable morbidity
      and mortality worldwide. There are few population-based studies on hypertension
      epidemiology to guide public health strategies in sub-Saharan Africa. Using a
      community-based strategy that integrated screening for HIV and non-communicable
      diseases, we determined the prevalence, awareness, treatment rates, and
      sociodemographic factors associated with hypertension in rural Uganda. METHODS: A
      household census was performed to enumerate the population in Kakyerere parish in
      Mbarara district, Uganda. A multi-disease community-based screening campaign for
      hypertension, diabetes, and HIV was then conducted. During the campaign, all
      adults received a blood pressure (BP) measurement and completed a survey
      examining sociodemographic factors. Hypertension was defined as elevated BP (>=
      140/>= 90 mmHg) on the lowest of three BP measurements or current use of
      antihypertensives. Prevalence was calculated and standardized to age
      distribution. Sociodemographic factors associated with hypertension were
      evaluated using a log-link Poisson regression model with robust standard errors.
      RESULTS: Community participation in the screening campaign was 65%, including
      1245 women and 1007 men. The prevalence of hypertension was 14.6%; awareness of
      diagnosis (38.1%) and current receipt of treatment (20.6%) were both low. Age
      standardized to the WHO world standard population, hypertension prevalence was
      19.8%, which is comparable to 21.6% in the US and 18.4% in the UK.
      Sociodemographic factors associated with hypertension included increasing age,
      male gender, overweight, obesity, diabetes, alcohol consumption, and family
      history. Prevalence of modifiable factors was high: 28.3% women were
      overweight/obese and 24.1% men consumed >= 10 alcoholic drinks per month.
      CONCLUSIONS: We found a substantial burden of hypertension in rural Uganda.
      Awareness and treatment of hypertension is low in this region. Enhanced community
      based education and prevention efforts tailored to addressing modifiable factors
      are needed.

PMID- 24321134
TI  - The role of multilevel factors in geographic differences in bicycle crash risk: a
      prospective cohort study.
AB  - BACKGROUND: Regular cycling plays an important role in increasing physical
      activity levels but raises safety concerns for many people. While cyclists bear a
      higher risk of injury than most other types of road users, the risk differs
      geographically. Auckland, New Zealand's largest urban region, has a higher injury
      risk than the rest of the country. This paper identified underlying factors at
      individual, neighbourhood and environmental levels and assessed their relative
      contribution to this risk differential. METHODS: The Taupo Bicycle Study involved
      2590 adult cyclists recruited in 2006 and followed over a median period of 4.6
      years through linkage to four national databases. The Auckland participants were
      compared with others in terms of baseline characteristics, crash outcomes and
      perceptions about environmental determinants of cycling. Cox regression modelling
      for repeated events was performed with multivariate adjustments. RESULTS: Of the
      2554 participants whose addresses could be mapped, 919 (36%) resided in Auckland.
      The Auckland participants were less likely to be Maori but more likely to be
      socioeconomically advantaged and reside in an urban area. They were less likely
      to cycle for commuting and off-road but more likely to cycle in the dark and in a
      bunch, use a road bike and use lights in the dark. They had a higher risk of on
      road crashes (hazard ratio: 1.47; 95% CI: 1.22, 1.76), of which 53% (95% CI: 20%,
      72%) was explained by baseline differences, particularly related to cycling off
      road, in the dark and in a bunch and residing in urban areas. They were more
      concerned about traffic volume, speed and drivers' behaviour. CONCLUSIONS: The
      excess crash risk in Auckland was explained by cycling patterns, urban residence
      and factors associated with the region's car-dominated transport environment.

PMID- 24321135
TI  - Constrictive pleuropericarditis: a dominant clinical manifestation in Whipple's
      disease.
AB  - BACKGROUND: Whipple's disease is a rare, multisystemic, chronic infectious
      disease which classically presents as a wasting illness characterized by
      polyarthralgia, diarrhea, fever, and lymphadenopathy. Pleuropericardial
      involvement is a common pathologic finding in patients with Whipple's disease,
      but rarely causes clinical symptoms. We report the first case of severe fibrosing
      pleuropericarditis necessitating pleural decortication in a patient with
      Whipple's disease. CASE PRESENTATION: Our patient, an elderly gentleman, had a
      chronic inflammatory illness dominated by constrictive pericarditis and later
      severe fibrosing pleuritis associated with a mildly elevated serum IgG4 level. A
      pericardial biopsy showed dense fibrosis without IgG4 plasmacytic infiltration.
      The patient received immunosuppressive therapy for possible IgG4-related disease.
      His poor response to this therapy prompted a re-examination of the diagnosis,
      including a request for the pericardial biopsy tissue to be stained for
      Tropheryma whipplei. CONCLUSIONS: Despite a high prevalence of pleuropericardial
      involvement in Whipple's disease, constrictive pleuropericarditis is rare,
      particularly as the dominant disease manifestation. The diagnosis of Whipple's
      disease is often delayed in such atypical presentations since the etiologic
      agent, Tropheryma whipplei, is not routinely sought in histopathology specimens
      of pleura or pericardium. A diagnosis of Whipple's disease should be considered
      in middle-aged or elderly men with polyarthralgia and constrictive pericarditis,
      even in the absence of gastrointestinal symptoms. Although Tropheryma whipplei
      PCR has limited sensitivity and specificity, especially in the analysis of
      peripheral blood samples, it may have diagnostic value in inflammatory disorders
      of uncertain etiology, including cases of polyserositis. The optimal approach to
      managing constrictive pericarditis in patients with Whipple's disease is
      uncertain, but limited clinical experience suggests that a combination of
      pericardiectomy and antibiotic therapy is of benefit.

PMID- 24321137
TI  - Identification of a novel pentatricopeptide repeat subfamily with a C-terminal
      domain of bacterial origin acquired via ancient horizontal gene transfer.
AB  - BACKGROUND: Pentatricopeptide repeat (PPR) proteins are a large family of
      sequence-specific RNA binding proteins involved in organelle RNA metabolism. Very
      little is known about the origin and evolution of these proteins, particularly
      outside of plants. Here, we report the identification of a novel subfamily of PPR
      proteins not found in plants and explore their evolution. RESULTS: We identified
      a novel subfamily of PPR proteins, which all contain a C-terminal tRNA guanine
      methyltransferase (TGM) domain, suggesting a predicted function not previously
      associated with PPR proteins. This group of proteins, which we have named the PPR
      TGM subfamily, is found in distantly related eukaryotic lineages including
      cellular slime moulds, entamoebae, algae and diatoms, but appears to be the first
      PPR subfamily absent from plants. Each PPR-TGM protein identified is predicted to
      have different subcellular locations, thus we propose that these proteins have
      roles in tRNA metabolism in all subcellular locations, not just organelles. We
      demonstrate that the TGM domain is not only similar to bacterial TGM proteins,
      but that it is most similar to chlamydial TGMs in particular, despite the absence
      of PPR proteins in bacteria. Based on our data, we postulate that this subfamily
      of PPR proteins evolved from a TGM-encoding gene of a member of the Chlamydiae,
      which was obtained via ancient prokaryote-to-eukaryote horizontal gene transfer.
      Following its acquisition, the N-terminus of the encoded TGM protein must have
      been extended to include PPR motifs, possibly to confer additional functions to
      the protein, giving rise to the PPR-TGM subfamily. CONCLUSIONS: The
      identification of a unique PPR subfamily which originated from the Chlamydiae
      group of bacteria offers novel insight into the origin and evolution of PPR
      proteins not previously considered. It also provides further understanding into
      their roles in non-organellar RNA metabolism.

PMID- 24321138
TI  - Effects of diesel exposure on lung function and inflammation biomarkers from
      airway and peripheral blood of healthy volunteers in a chamber study.
AB  - BACKGROUND: Exposure to diesel exhaust causes inflammatory responses. Previous
      controlled exposure studies at a concentration of 300 MUg/m(3) of diesel exhaust
      particles mainly lasted for 1 h. We prolonged the exposure period and
      investigated how quickly diesel exhaust can induce respiratory and systemic
      effects. METHODS: Eighteen healthy volunteers were exposed twice to diluted
      diesel exhaust (PM1 ~300 MUg/m(3)) and twice to filtered air (PM1 ~2 MUg/m(3))
      for 3 h, seated, in a chamber with a double-blind set-up. Immediately before and
      after exposure, we performed a medical examination, spirometry, rhinometry, nasal
      lavage and blood sampling. Nasal lavage and blood samples were collected again 20
      h post-exposure. Symptom scores and peak expiratory flow (PEF) were assessed
      before exposure, and at 15, 75, and 135 min of exposure. RESULTS: Self-rated
      throat irritation was higher during diesel exhaust than filtered air exposure.
      Clinical signs of irritation in the upper airways were also significantly more
      common after diesel exhaust exposure (odds ratio = 3.2, p<0.01). PEF increased
      during filtered air, but decreased during diesel exhaust exposure, with a
      statistically significant difference at 75 min (+4 L/min vs. -10 L/min, p =
      0.005). Monocyte and total leukocyte counts in peripheral blood were higher after
      exposure to diesel exhaust than filtered air 20 h post-exposure, and a trend (p =
      0.07) towards increased serum IL-6 concentrations was also observed 20 h post
      exposure. CONCLUSIONS: Diesel exhaust induced acute adverse effects such as
      symptoms and signs of irritation, decreased PEF, inflammatory markers in healthy
      volunteers. The effects were first seen at 75 min of exposure.

PMID- 24321139
TI  - BTLA as a biomarker and mediator of sepsis-induced immunosuppression.
AB  - Recent research indicates that T-lymphocyte dysfunction may contribute to sepsis
      associated morbidity and mortality. B and T lymphocyte attenuator (BTLA) is a co
      inhibitory receptor expressed by T lymphocytes and B lymphocytes that is
      important in regulating lymphocyte activation during inflammation and infection.
      Shubin and colleagues report that higher mean BTLA expression in critically ill
      patients may have value in identifying patients with infection. Further studies
      provide evidence that BTLA activation contributes to T-lymphocyte apoptosis
      during sepsis. Although this study will require follow-up and further
      investigation, the results advance current knowledge regarding potential
      mechanisms underlying sepsis-induced immunosuppression and identify BTLA as a
      candidate biomarker and mediator of T-cell dysfunction during sepsis. 

PMID- 24321140
TI  - Quantitative measurements of the ciliary body in eyes with malignant glaucoma
      after trabeculectomy using ultrasound biomicroscopy.
AB  - PURPOSE: To evaluate and compare the structural differences of the ciliary body
      in eyes with and without malignant glaucoma. DESIGN: Cross-sectional study.
      PARTICIPANTS: Twenty-seven consecutive patients diagnosed with malignant glaucoma
      in 1 eye after trabeculectomy were recruited. They were all originally diagnosed
      with primary angle closure (PAC) or PAC glaucoma (PACG). Twenty-seven PAC/PACG
      eyes of 27 patients who had undergone uneventful trabeculectomy in the same
      period were also recruited. They were comparable with the fellow eyes of the
      malignant glaucoma patients in terms of surgical type, glaucoma type, and stage.
      METHODS: A-scan ultrasonography and ultrasound biomicroscopy measurements were
      performed on the eyes with malignant glaucoma, the fellow eyes of the patients
      with malignant glaucoma, and the matched eyes. MAIN OUTCOME MEASUREMENTS: Ciliary
      body parameters included maximum ciliary body thickness (CBTmax), ciliary body
      thickness at the point of the scleral spur (CBT0) and 1000 MUm from the scleral
      spur (CBT1000), anterior placement of the ciliary body (APCB), and the trabecular
      ciliary process angle (TCA). Biometric measurements including axial length,
      central anterior chamber depth (ACD), pupil diameter (PD), anterior chamber
      width, and lens vault (LV) were also recorded. RESULTS: Average CBTmax were
      0.545+/-0.088 (mean +/- standard deviation), 0.855+/-0.170, and 0.960+/-0.127 mm
      in eyes with malignant glaucoma, their fellow eyes, and the matched eyes,
      respectively. Average APCB were 0.860+/-0.176, 0.608+/-0.219, and 0.427+/-0.139
      mm, respectively. Average TCA were 18.49+/-4.12, 41.79+/-17.27, and 48.53+/-10.38
      degrees, respectively. The CBTmax, CBT0, CBT1000, and TCA were smaller, whereas
      APCB was larger in eyes with malignant glaucoma compared with their fellow eyes
      (P < 0.01). The fellow eyes had larger APCB and smaller CBTmax and CBT0 than the
      matched eyes (P < 0.05). The ACD, anterior chamber width, and PD were smaller,
      whereas LV was larger in eyes with malignant glaucoma compared with their fellow
      eyes (P < 0.05). No differences were found in the ACD, anterior chamber width,
      PD, or LV between the fellow eyes of malignant glaucoma and matched eyes (P >
      0.1). CONCLUSIONS: The ciliary bodies were thinner and more anteriorly rotated in
      eyes with malignant glaucoma as well as in their fellow eyes, which may be the
      predisposing factor for malignant glaucoma.

PMID- 24321141
TI  - Diagnosing ocular surface squamous neoplasia in East Africa: case-control study
      of clinical and in vivo confocal microscopy assessment.
AB  - OBJECTIVE: To examine the reliability of clinical examination and in vivo
      confocal microscopy (IVCM) in distinguishing ocular surface squamous neoplasia
      (OSSN) from benign conjunctival lesions. DESIGN: Case-control study.
      PARTICIPANTS: Sixty individuals with conjunctival lesions (OSSN and benign) and
      60 age-matched controls with normal conjunctiva presenting to Kilimanjaro
      Christian Medical Centre, Moshi, Tanzania. METHODS: Participants were examined
      and photographed, and IVCM was performed. Patients with conjunctival lesions were
      offered excisional biopsy with histopathology and a human immunodeficiency virus
      (HIV) test. The IVCM images were read masked to the clinical appearance and
      pathology results. Images were graded for several specific features and given an
      overall categorization (normal, benign, or malignant). A group of 8
      ophthalmologists were shown photographs of conjunctival lesions and asked to
      independently classify as OSSN or benign. MAIN OUTCOME MEASURES: Comparison of
      the histopathology diagnosis with the clinical and IVCM diagnosis. RESULTS: Fifty
      two cases underwent excisional biopsy with histopathology; 34 were on the OSSN
      spectrum, 17 were benign, and 1 was lymphoma. The cases and controls had
      comparable demographic profiles. Human immunodeficiency syndrome infection was
      more common in OSSN compared with benign cases (58.8% vs. 5.6%; odds ratio, 24.3,
      95% confidence interval [CI], 2.8-204; P = 0.003). Clinically, OSSN lesions more
      frequently exhibited feeder vessels and tended to have more leukoplakia and a
      gelatinous appearance. Overall, the ophthalmologists showed moderate agreement
      with the histology result (average kappa = 0.51; 95% CI, 0.36-0.64). The masked
      grading of IVCM images reliably distinguished normal conjunctiva. However, IVCM
      was unable to reliably distinguish between benign lesions and OSSN because of an
      overlap in their appearance (kappa = 0.44; 95% CI, 0.32-0.57). No single feature
      was significantly more frequent in OSSN compared with benign lesions. The
      sensitivity and specificity of IVCM for distinguishing OSSN from benign
      conjunctival lesions were 38.5% and 66.7%, respectively. CONCLUSIONS: In East
      Africa, conjunctival pathology is relatively common and can present significant
      diagnostic challenges for the clinician. In this study, neither clinical
      examination nor IVCM was found to reliably distinguish OSSN from benign
      conjunctival pathology because of an overlap in the features of these groups.
      Therefore, IVCM cannot currently replace histopathology, and management decisions
      should continue to rely on careful clinical assessment supported by
      histopathology as indicated.

PMID- 24321143
TI  - Results of toric intraocular lenses for post-penetrating keratoplasty
      astigmatism.
AB  - PURPOSE: Evaluate the usefulness of toric intraocular lens (IOL) implantation
      during cataract surgery in patients after penetrating keratoplasty (PKP). DESIGN:
      Retrospective case review. PARTICIPANTS: A total of 21 eyes of 16 patients with
      prior PKP and moderate to high regular astigmatism after full suture removal
      underwent phacoemulsification and implantation of a single-piece acrylic toric
      IOL (SN6AT series; Alcon, Fort Worth, TX). METHODS: Patients underwent
      comprehensive examinations at standard intervals, including visual acuity,
      manifest refraction, and corneal topography. MAIN OUTCOME MEASURES: Uncorrected
      distance visual acuity (UDVA) and corrected distance visual acuity (CDVA)
      expressed as the logarithm of the minimum angle of resolution (logMAR) and
      manifest refraction astigmatism. RESULTS: From preoperatively to the last visit
      (mean, 14.7 +/- standard deviation 12.8 months), the 21 eyes had significant
      improvement in UDVA (logMAR, 0.90 +/- 0.48 to 0.23 +/- 0.25; P = 0.0001) and CDVA
      (logMAR, 0.31 +/- 0.14 to 0.08 +/- 0.13; P = 0.0001). A total of 14 of 21 eyes
      (67%) and 17 of 21 eyes (81%) had UDVA and CDVA of >= 20/30, respectively.
      Preoperative topographic astigmatism was 4.57 +/- 2.05 diopters (D).
      Postoperative manifest refraction astigmatism was 1.58 +/- 1.25 D overall, but
      lower (0.75 +/- 0.54 D) in the T7-T9 subgroup (excluding 1 outlier whose corneal
      astigmatism doubled after surgery) than in the T4-T6 subgroup (1.88 +/- 1.28 D; P
      = 0.013). A total of 16 of all 21 eyes (76.2%) and 8 of 9 eyes (89%) in the T7-T9
      subgroup were within 1 D of postoperative manifest astigmatism as predicted or
      better. CONCLUSIONS: Toric IOLs placed during cataract surgery after PKP and full
      suture removal can reduce manifest refraction cylinder to predictably low levels
      with corresponding improvement in UDVA and CDVA in patients with moderate to high
      regular preoperative topographic astigmatism.

PMID- 24321142
TI  - Incidence, types, and lifetime risk of adult-onset strabismus.
AB  - OBJECTIVE: To describe the incidence and types of adult-onset strabismus in a
      geographically defined population. DESIGN: Retrospectively reviewed population
      based cohort. PARTICIPANTS: All adult (>=19 years of age) residents of Olmsted
      County, Minnesota, diagnosed with new-onset adult strabismus from January 1,
      1985, through December 31, 2004. METHODS: The medical records of all potential
      cases identified by the resources of the Rochester Epidemiology Project were
      reviewed. MAIN OUTCOME MEASURES: Incidence rates for adult-onset strabismus and
      its types. RESULTS: Seven hundred fifty-three cases of new-onset adult strabismus
      were identified during the 20-year period, yielding an annual age- and gender
      adjusted incidence rate of 54.1 cases (95% confidence interval, 50.2-58.0) per
      100 000 individuals 19 years of age and older. The 4 most common types of new
      onset strabismus were paralytic (44.2% of cases), convergence insufficiency
      (15.7%), small-angle hypertropia (13.3%), and divergence insufficiency (10.6%).
      The incidence of adult-onset strabismus overall and its 4 most common forms
      significantly increased with age (P <0.001 for all), with a peak incidence in the
      eighth decade of life. The lifetime risk of being diagnosed with adult-onset
      strabismus was 4.0% in women and 3.9% in men. CONCLUSIONS: Paralytic strabismus
      was the most common subtype of new-onset adult strabismus in this population
      based cohort. All of the most common forms of adult-onset strabismus increased
      with age, especially after the sixth decade of life. Further characterization of
      strabismus types found in this study is warranted to better define this disorder.

PMID- 24321144
TI  - Differentiating mild papilledema and buried optic nerve head drusen using
      spectral domain optical coherence tomography.
AB  - PURPOSE: To evaluate the clinical utility of spectral domain optical coherence
      tomography (SD-OCT) in differentiating mild papilledema from buried optic nerve
      head drusen (ONHD). DESIGN: Comparative case series. PARTICIPANTS: Sixteen eyes
      of 9 patients with ultrasound-proven buried ONHD, 12 eyes of 6 patients with less
      than or equal to Frisen grade 2 papilledema owing to idiopathic intracranial
      hypertension. Two normal fellow eyes of patients with buried ONHD were included.
      METHODS: A raster scan of the optic nerve and analysis of the retinal nerve fiber
      layer (RNFL) thickness was performed on each eye using SD-OCT. Eight eyes
      underwent enhanced depth imaging SD-OCT. Images were assessed qualitatively and
      quantitatively to identify differentiating features between buried ONHD and
      papilledema. Five clinicians trained with a tutorial and masked to the underlying
      diagnosis independently reviewed the SD-OCT images of each eye to determine the
      diagnosis. MAIN OUTCOME MEASURES: Differences in RNFL thickness in each quadrant
      between the 2 groups and diagnostic accuracy of 5 independent clinicians based on
      the SD-OCT images alone. RESULTS: We found no difference in RNFL thickness
      between buried ONHD and papilledema in any of the 4 quadrants. Diagnostic
      accuracy among the readers was low and ranged from 50% to 64%. The kappa
      coefficient of agreement among the readers was 0.35 (95% confidence interval,
      0.19-0.54). CONCLUSIONS: We found that SD-OCT is not clinically reliable in
      differentiating buried ONHD and mild papilledema.

PMID- 24321146
TI  - Detection and isolation of 2009 pandemic influenza A/H1N1 virus in commercial
      piggery, Lagos Nigeria.
AB  - WHO declared pandemic of A/H1N1 influenza in 2009 following global spread of the
      newly emerged strain of the virus from swine. Presently there is a dearth of data
      on the ecology of pandemic influenza H1N1 required for planning of intervention
      measures in sub Saharan Africa. Herein we report isolation of 2009 pandemic
      influenza A/H1N1 in an intensive mega piggery farms operation in South West
      Nigeria. Sentinel surveillance was carried out in a cohort of intensively reared
      pigs over a period of two years. Nasal swab specimens were collected at monthly
      interval from observed clinical cases of influenza like illness in pigs and pig
      handlers. Samples were analyzed by real time RT-PCR and isolation in chicken
      embryonated eggs. A total of 227 clinical cases of influenza like illness were
      observed among pigs out of which 31 (13.7%) were positive for influenza A matrix
      gene by real time RT-PCR. Virus isolation yielded 29 (12%) isolates out of which
      18 (18%) were identified as influenza A/H1N1 by Heamaglutination Inhibition test
      using H1 antisera. RT-PCR positive samples were subtyped as 2009 pandemic A/H1N1
      with subtype specific primers and probes. This is the first report of detection
      and isolation of pandemic influenza H1N1 from pigs in Nigeria. Continuous
      circulation of this virus in pigs may cause reassortments with seasonal influenza
      or mutations and substitutions in the gene that may result in the emergence of
      novel or pandemic influenza virus of economic and public health importance.
      Nigeria is considered a geographical hotspot of zoonotic diseases, which
      necessitate active surveillance and monitoring of emerging pandemic threats.

PMID- 24321147
TI  - Asymptomatic MS.
AB  - "Asymptomatic multiple sclerosis (MS)" or "subclinical MS" describes "a
      clinically silent disease state of MS" discovered by chance either by imaging or
      at autopsy, or with incidental findings shown by other diagnostic tools that are
      consistent or suggestive of MS, and that cannot be explained by any other disease
      or condition. Since the early 1960s there have been a number of autopsy studies
      reporting cases, in which histopathological brain changes consistent with MS were
      found, despite that none had any clinical symptom or sign of the disease during
      their lifetime. Several reports have also shown that asymptomatic first-degree
      relatives of MS patients may have oligoclonal bands in their cerebrospinal fluids
      or may turn out to have abnormal evoked potential studies. With the extensive
      availability of MRI lately, the incidence of individuals having these studies
      performed for indications other than suspicion of inflammatory demyelinating
      disease of the central nervous system (CNS) such as primary headaches or trauma,
      revealing unsuspected brain and/or spinal cord lesions compatible with MS had
      raised. A number of such case-series reported recently had resulted in increased
      awareness of this finding and to its relationship to clinical multiple sclerosis.
      This situation is now referred as "radiologically isolated syndrome (RIS)" and is
      the most common type of "asymptomatic MS". Since it is well known that MS has an
      asymptomatic period of unknown duration in many individuals preceding its initial
      presentation, either as a clinically isolated syndrome or in rare instances as
      primary progressive-MS, it is likely that a number of MS patients will be
      diagnosed by chance as RIS at an early stage before converting to clinical
      disease. Currently this issue has gained a wide interest as there are no
      established protocols regarding how to study and follow these individuals or
      whether they should be treated or not! However, not all patients with RIS are
      predestined to develop clinical disease and it was recently shown that the rate
      of conversion to clinical MS is about one-third of RIS cases at five years.
      Although that there may be some risk factors suggestive of a higher or earlier
      conversion to clinical disease, none are definite and the current evidence is not
      supportive of initiating treatment in patients diagnosed as RIS. 

PMID- 24321145
TI  - Body composition and arsenic metabolism: a cross-sectional analysis in the Strong
      Heart Study.
AB  - OBJECTIVE: The objective of this study was to evaluate the association between
      measures of body composition and patterns of urine arsenic metabolites in the
      1989-1991 baseline visit of the Strong Heart Study, a cardiovascular disease
      cohort of adults recruited from rural communities in Arizona, Oklahoma, North
      Dakota and South Dakota. METHODS: We evaluated 3,663 Strong Heart Study
      participants with urine arsenic species above the limit of detection and no
      missing data on body mass index, % body fat and fat free mass measured by
      bioelectrical impedance, waist circumference and other variables. We summarized
      urine arsenic species patterns as the relative contribution of inorganic (iAs),
      methylarsonate (MMA) and dimethylarsinate (DMA) species to their sum. We modeled
      the associations of % arsenic species biomarkers with body mass index, % body
      fat, fat free mass, and waist circumference categories in unadjusted regression
      models and in models including all measures of body composition. We also
      considered adjustment for arsenic exposure and demographics. RESULTS: Increasing
      body mass index was associated with higher mean % DMA and lower mean % MMA before
      and after adjustment for sociodemographic variables, arsenic exposure, and for
      other measures of body composition. In unadjusted linear regression models, % DMA
      was 2.4 (2.1, 2.6) % higher per increase in body mass index category (< 25, >=25
      & <30, >=30 & <35, >=35 kg/m2), and % MMA was 1.6 (1.4, 1.7) % lower. Similar
      patterns were observed for % body fat, fat free mass, and waist circumference
      measures in unadjusted models and in models adjusted for potential confounders,
      but the associations were largely attenuated or disappeared when adjusted for
      body mass index. CONCLUSION: Measures of body size, especially body mass index,
      are associated with arsenic metabolism biomarkers. The association may be related
      to adiposity, fat free mass or body size. Future epidemiologic studies of arsenic
      should consider body mass index as a potential modifier for arsenic-related
      health effects.

PMID- 24321148
TI  - Profile of depression, experienced distress and capacity for coping with stress
      in multiple sclerosis patients--a different perspective.
AB  - Multiple sclerosis (MS) can result in significant changes in psychological
      functioning. Depression and cognitive deficits are commonly present. In addition
      personality changes have been described. A growing body of research is showing
      negative impact of psychological stress on disease course. Our study focused on
      the profile of depression, capacity for coping with stress and experienced
      distress in patients with MS measured by a performance based method for
      personality assessment-the Rorschach Inkblot Method (RIM). We included 95
      patients with MS and 44 healthy controls. RIM was used with all participants and
      was scored by the Exner Comprehensive system. Compared to healthy controls MS
      patients had statistically significantly lower capacity for coping with stress,
      complexity of information processing, body image, willingness to process
      emotional stimulation and interpersonal interest. Surprisingly patients had lower
      experienced distress than controls. We propose that the profile of depression in
      advanced MS disease might be better described in terms of negative symptoms such
      as emotional withdrawal and apathy and less with the profile of positive symptoms
      such as rumination and worry. RIM variables were not significantly associated
      with the EDSS. Interventions from which patients could benefit are discussed. 

PMID- 24321149
TI  - Subjective and perceptual analysis of voice quality and relationship with
      neurological disfunction in multiple sclerosis patients.
AB  - OBJECTIVE: The aim of the present study was to evaluate subjective voice changes
      by voice handicap index (VHI) and voice related quality of life questionnaire
      (VRQL) and perceptual voice changes by Grade Roughness Breathiness Asthenia
      Strain (GRBAS) scale and to compare these findings with expanded disability
      status scale (EDSS) in multiple sclerosis (MS) patients. METHODS: The patient
      group was composed of 36 MS patients, (mean age 45.2 +/- 12.9, 13 male and 23
      female) and compared with 32 healthy sex and age match individuals without
      neurological and voice symptoms. RESULTS: The mean VHI was significantly higher
      in patients group (15.64 to 5.43; p=0.043). Forty-four percent of MS patients
      (52% of female patients) report voice problems. According to the GRBAS scale,
      differences between two groups were significant for Grade, Roughness, Breathiness
      and Strain items. The mean EDSS was 2.69 +/- 1.1, for a male patients 2.54 +/-
      1.1 and for female 2.78 +/- 1.3. There was no correlation between the EDSS and
      the total VHI score, between the EDSS and each of the three item of VHI, between
      the EDSS and VRQL, nor between the EDSS and components of GRBAS scale except for
      EDSS and asthenia item, (r=-0.5213, p=0.011). CONCLUSIONS: Significant number of
      MS patients experienced voice problems. We did not establish any significant
      correlation between the intensity of the voice disorders and EDSS, except between
      EDSS and asthenia item of the GRBAS scale. The patients with low EDSS may have
      serious voice problems and vice versa.

PMID- 24321150
TI  - Treatment of multiple sclerosis and neuromyelitis optica in children and
      adolescents.
AB  - Paediatric multiple sclerosis (MS) accounts for up to 5% of all MS cases. No
      therapies have been formally approved for paediatric patients with MS. However,
      there is published experience on the use of disease modifying therapies in
      children and adolescents with MS. Neuromyelitis optica (NMO) is an autoimmune
      inflammatory disease preferentially targeting the optic nerves and spinal cord.
      This devastating disease usually requires preventive therapy with a range of
      immunosuppressive medications. There are limited studies informing the use of
      these medications in children with NMO. This review provides a comprehensive
      analysis of the published literature on therapeutic interventions in children and
      adolescents with MS and NMO. 

PMID- 24321151
TI  - Challenges in multiple sclerosis; how to define occurence of progression.
AB  - The challenges in MS are related to number of controversies in various aspects of
      disease but the relationship between relapses and disability progression, or
      aspects of MS as an inflammatory and/or neurodegenerative disease are extremely
      important because of its implications on prognosis and therapy of MS. MS was
      classically regarded as white matter inflammatory disease, while disability
      progression, brain and spinal cord atrophy were regarded as a consequence of
      global inflammation of NAWM and secondary involvement of grey matter. More recent
      histopathology studies, but also new, modern MRI techniques changed this view in
      MS as a prominent grey and white matter disease. Inflammatory demyelination of
      grey matter occurs early in MS sometimes even before occurrence of white matter
      lesions. Inspite of early therapy of MS with immunomodulatory drugs disability
      progression and neurodegeneration are still important and common part of MS
      pathogenesis. This indicate that treatment is not adequate to the predicted
      severity of MS, or perhaps to the basic pathogenetic mechanisms in MS. Beside
      acute clinical symptoms, conclusions about the severity of the disease are
      reflection of MRI sensitivity to detect focal WM lesions and insensitivity to
      detect grey matter lesions which correlate better with clinical symptoms. All
      presented studies and evaluations point to the necessity of changing the
      established diagnostic evaluation and treatment in MS. At the earliest stage of
      MS as well as in follow up of disease it would be necessary to apply a new MRI
      techniques more available for clinical practice such as DIR brain MR imaging at
      3T because of their sensitivity to detect grey matter lesions. In patient with
      present cortical lesions even in earliest stages of MS depending on severity of
      grey matter involvement more efficacious therapy like second or even third line
      therapy should start. 

PMID- 24321152
TI  - Acute disseminated encephalomyelitis associated with hepatitis B virus
      reinfection--consequence or coincidence?
AB  - Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory
      demyelinating disease of the CNS that is particularly difficult to differentiate
      from the first episode of multiple sclerosis. ADEM typically occurs as a post
      infectious phenomenon, and usually presents a monophasic episode, but also
      includes recurrent and multiphasic forms. We report a case of ADEM associated
      with hepatitis B virus (HBV) reinfection. After steroid and IV immunoglobulin
      treatment, neurologic symptoms were improved. We suppose that the HBV reinfection
      was the cause of ADEM, but possible pathogenetic mechanism is still obscure. 

PMID- 24321153
TI  - Recent insights into the pathology of multiple sclerosis and neuromyelitis
      optica.
AB  - Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of
      the central nervous system. Traditionally, demyelinating lesions in the white
      matter have been regarded as the most important pathological feature in MS, but
      recent pathological and imaging studies confirmed substantial changes in grey
      matter and normal-appearing white matter. MS lesions are characterized by
      inflammation, demyelination, axonal damage and astrogliosis. During early MS
      lesion formation acute axonal injury is extensive and correlates with
      inflammation. In addition to focal lesions, diffuse wide-spread changes including
      neuroaxonal degeneration and compartmentalized inflammation are likely to
      contribute to increasing disability in progressive MS. Neuromyelitis optica (NMO)
      is classically characterized by severe transverse myelitis and optic neuritis,
      but brain lesions are also present in the majority of NMO patients. The discovery
      of the NMO-specific antibody demonstrated that NMO is a disease entity distinct
      from MS. This antibody binds to aquaporin-4 expressed in astrocytes and ependymal
      cells. NMO lesions are characterized by inflammation, demyelination, axonal
      damage and a marked loss of aquaporin-4. Early NMO lesions demonstrate a
      pronounced humoral inflammatory response and astrocytic cell death with loss of
      aquaporin-4, followed by inflammatory demyelination and axonal damage. These
      recent findings contribute to a better understanding of different mechanisms
      leading to inflammatory demyelination. 

PMID- 24321154
TI  - Development of gray matter atrophy in relapsing-remitting multiple sclerosis is
      not gender dependent: results of a 5-year follow-up study.
AB  - OBJECTIVES: The aim of this study was to explore the evolution of MRI related
      gender differences in patients with relapsing-remitting (RR) multiple sclerosis
      (MS) who participated in a clinical trial over the 5 years. METHODS: 181 patients
      (39 males and 142 females) were assessed for clinical and neuroradiological
      disease activity over a period of 5 years. Clinical and MRI examination were
      performed at the baseline, 6, 12, 24, 36, 48 and 60 months. Longitudinal
      percentage volume changes in whole brain (PBVC), gray matter (PGMVC) white matter
      (PWMVC) cortex (PCVC), and lateral ventricles (PLVVC) were calculated by using
      direct methods (SIENA and SIENAX-multitimepoint). Absolute tissue volume changes
      of subcortical deep GM structures including caudate, putamen, globus pallidus,
      thalamus, hippocampus, amygdala and nucleus accumbens were estimated using FIRST,
      a model based segmentation/registration tool. T2 lesion volume (T2-LV) and lesion
      activity analyses were performed, using a contouring-threshold and subtraction
      techniques. All clinical and MRI variables were analyzed between males and
      females. RESULTS: Global (PBVC) and tissue specific (PGMVC, PWMVC, PCVC, PLVVC)
      brain volume changes showed no significant gender differences over the 5-year
      follow-up period. Although total subcortical deep GM, caudate, putamen, globus
      palidus, thalamus and nucleus accumbens normalized volumes were significantly
      larger in male subjects at baseline, the follow-up analysis showed no differences
      over the 5 years. There were no gender differences in lesion activity or T2-LV
      changes over the 5 years. CONCLUSION: No MRI lesion, global, tissue specific or
      regional brain volume gender change differences were found over the 5-year follow
      up.

PMID- 24321155
TI  - Retinal nerve fiber thickness and MRI white matter abnormalities in healthy
      relatives of multiple sclerosis patients.
AB  - OBJECTIVES: To compare retinal nerve fiber (RNFL) thickness and conventional and
      non-conventional MRI characteristics of healthy controls (HCs) from the general
      population (non-fHC) to healthy relatives of multiple sclerosis (MS) patients
      (fHC). METHODS: Sixty-eight (68) HCs underwent optical coherence tomography (OCT)
      and 3T MRI examination. Subjects were classified based on whether or not there
      was a family history of MS. The study enrolled 40 non-fHC who had no relatives
      with MS and 28 fHC with at least one relative affected with MS. The associations
      between OCT parameters and conventional and non-conventional MRI measures were
      investigated. RESULTS: There were no significant OCT or conventional and non
      conventional MRI measureable differences between the non-fHC and fHC groups.
      Periventricular localization and total volume of white matter (WM) signal
      abnormalities (SA) were more common in the fHC group but the differences did not
      reach a level of significance. A significant association between decreased RNFL
      thickness with increased volume (p=0.001), number (p=0.003) and frequency of >= 9
      T2 (p=0.003) WM SAs on MRI was found in the fHC group. No association between OCT
      and MRI parameters was detected in the non-fHC group. CONCLUSION: There is an
      association between decreased RNFL thickness on OCT and increased WM injury in
      healthy relatives of MS patients. Further studies should explore the
      pathophysiology of these findings.

PMID- 24321156
TI  - Perspectives of an innovative ophthalmological technology: optical coherence
      tomography (OCT)--what should be of interest to the neurologist?
AB  - Ocular coherence tomography has revolutionised the prospects of measuring the
      loss of retinal ganglion cells secondary to degenerative diseases and monitoring
      time-dependent changes of optic disc morphology, since the resolution has been
      improved considerably and the time required has been reduced. Although the non
      invasive technique promises a high inter-session reproducibility, the limitations
      of retinal imaging and the problems of segmenting of the retinal layers have to
      be taken into account. While the first studies were limited to single sessions in
      small groups, further trials will elucidate how the retinal nerve fibre layer
      (RNFL) is altered in the course of different episodic forms of multiple
      sclerosis. This review points out that the examination technique already provides
      comprehensive information, valuable in the daily care of neurological patients. 

PMID- 24321157
TI  - Adherence to disease-modifying therapies and attitudes regarding disease in
      patients with multiple sclerosis.
AB  - Although currently there is no cure for MS the course of the disease can be
      influenced by disease modifying therapy (DMT). For therapy to be sufficiently
      efficient, it is crucial that patients take their medication regularly as
      prescribed. Adherence describes the extent to which a patient acts in accordance
      with the prescribed timing, dosing, and frequency of medication administration.
      To date, there are no known data about adherence rates among patients with MS in
      Slovenia. We wanted to assess adherence in patients with MS, who are treated with
      first line DMTs and discover reasons for non-adherence. A number of 451 patients
      were invited to participate. They received two questionnaires via post mail. The
      adherence rate and putative reasons for non-adherence were assessed by the use of
      standardized self-report Multiple Sclerosis Treatment Experience Questionnaire
      (MSTEQ). Patients' attitudes regarding disease, therapy and relationship with
      their physician were assessed by another questionnaire. The analysis of results
      included 299 patients. Among the patients 18.5% missed at least one medication
      dose in the past 28 days. Patients taking Avonex were significantly more adherent
      then patients on other DMTs (p=0.005). Our study showed a higher then expected
      adherence among Slovenian patients with MS (81.5%). Our research did not confirm
      the influence of side effects or patients' attitudes regarding illness and
      therapy on adherence. However we found unexpectedly high percentage (71.8%) of
      patients belief that psychological factors are involved in MS aetiology. 

PMID- 24321158
TI  - Management of fingolimod in clinical practice.
AB  - The efficacy of the innovative oral drug fingolimod has been proven in the
      largest study program in multiple sclerosis (MS) demonstrating reduced relapse
      and reduced disability progression in relapsing-remitting MS patients. Based on
      the extensive safety data of all clinical trials and the natural distribution
      pattern of fingolimod interacting receptors in organism, careful clinical
      monitoring is recommend and reviewed in this paper. Safety and tolerability data
      from clinical studies as well as current post-marketing experience present with
      high tolerability and easy-to-perform management of fingolimod. Here we present
      the recommended management of fingolimod in clinical practice starting with
      preparatory steps, first-dose application and long-term treatment period with
      fingolimod. This management of fingolimod in clinical practice ensure a safe
      treatment algorithm using fingolimod. We recommend documentation of fingolimod
      patients in clinical registries to generate postmarketing data on efficacy and
      safety of fingoilimod. 

PMID- 24321160
TI  - Delay in the diagnosis of multiple sclerosis in Croatia.
AB  - BACKGROUND: The National Institute for Health and Clinical Excellence (NICE)
      guidelines for multiple sclerosis (MS) recommend the time from initial
      presentation to first neurological evaluation to be no longer than 6 weeks, and a
      further 6 weeks until any necessary investigations are completed. The aim of this
      study was to evaluate how many patients with MS are diagnosed within the NICE
      timelines in two settings specific for Croatia. PATIENTS AND METHODS: All
      patients with the final diagnosis of clinically isolated syndrome (CIS) or MS in
      a 6 months period were retrospectively reviewed. We calculated time from first
      symptom to first neurological evaluation, time from first symptom to MRI scan,
      time from first neurological evaluation to MRI scan, time from first neurological
      evaluation to lumbar puncture (LP), time from first symptom to diagnosis and time
      from first neurological evaluation to diagnosis. We also calculated the
      percentage of patients fulfilling the NICE timelines. RESULTS: This study showed
      that only 61.5% of MS patients in Croatia see neurologist within 6 weeks of first
      symptoms, and 64.1% are diagnosed within next 6 weeks. However, 80% and 100% of
      patients presented to the emergency room of our hospital (where a visit to a MS
      clinic can be automatically made) met the NICE guidelines for time from first
      symptom to first neurological evaluation and time from first neurological
      evaluation to diagnosis, respectively. CONCLUSION: A specifically designed
      demyelinating disease diagnostic clinic offers a better service than other
      existing models in the diagnosis and management of MS patients.

PMID- 24321159
TI  - Interferon-beta and disability progression in relapsing-remitting multiple
      sclerosis.
AB  - OBJECTIVE: To assess the impact of interferon (IFN)-beta treatment on the
      progression of unremitting disability in IFN-beta treated and untreated relapsing
      remitting (RR) patients with multiple sclerosis (MS) using prospective cohort
      study. METHODS: A cohort of 419 RRMS (236 IFN-beta-treated and 183 untreated)
      patients was followed for up to 7 years. Cox proportional hazards regression
      models adjusted for the number of relapses in the last year before first visit
      was used to assess the differences between the two groups for the three end
      points: secondary progression (SP), and sustained Expanded Disability Status
      Scale (EDSS) score 4 and 6. Time from disease onset was used as survival time
      variable. RESULTS: The IFN-beta-treated group showed a highly significant
      reduction (hazard ratio [HR], 0.34, 95% confidence interval [CI] 0.19-0.61,
      p<0.001) in the risk of SP when compared with untreated patients. There were
      significant differences in favor of the IFN-beta-treated group for the end point
      EDSS score of 4 (HR=0.45, 95%CI 0.28-0.73, p=0.001) and EDSS score of 6 (HR=0.34,
      95%CI 0.16-0.75, p=0.007). CONCLUSION: This observational study further supports
      the notion that IFN-beta could have potential beneficial effect on disease
      progression in RRMS.

PMID- 24321161
TI  - Autonomic dysfunction in multiple sclerosis.
AB  - Multiple sclerosis (MS) is the leading cause of neurological disability in young
      adults. Since the pathophysiology of MS is characterized by dissemination in
      space, as well as in time, the autonomic nervous system is inevitably damaged in
      the course of the disease in many patients and the proportion of affected
      patients increases with disease duration. Autonomic dysfunction (AD) in MS is
      explained by lesions in regions responsible for autonomic regulation such as
      nuclei in the periventricular region of fourth ventricle in the brainstem as well
      as medullar lesions. Reports about frequency of AD in MS patients vary notably
      between groups. Nevertheless its impact on quality of life is substantial but,
      unfortunately, often overlooked. The aim of this article is to present a concise
      review of various symptoms and signs of autonomic system dysfunction in MS. 

PMID- 24321162
TI  - Interferons beta have vasoconstrictive and procoagulant effects: a woman who
      developed livedo reticularis and Raynaud phenomenon in association with
      interferon beta treatment for multiple sclerosis.
AB  - A 31-year-old woman with MS developed livedo reticularis and secondary Raynaud
      phenomenon 2.5 years after introduction of interferon beta-1b. The symptoms
      disappeared after withdrawal of the drug. Livedo reticularis and Raynaud
      phenomenon as well as pulmonary arterial hypertension, venous sinus thrombosis,
      pulmonary embolism and renal thrombotic microangiopathy have all been described
      in association with interferon beta therapy. These complications strongly suggest
      that type I interferons have vasoconstrictive and procoagulant effects with
      potentially serious systemic complications. 

PMID- 24321163
TI  - Pathophysiological background and clinical characteristics of sleep disorders in
      multiple sclerosis.
AB  - Sleep disorders in multiple sclerosis (MS) are more common than in general
      population and are considered to be one of the important etiological factors in
      development of fatigue, most common and debilitating symptom of MS. Although
      almost all of the major subgroups of sleep disorders such as insomnia, sleep
      disordered breathing, REM sleep behavior disorder, narcolepsy and restless legs
      syndrome have been described in the MS patients their higher prevalence in MS
      population than in healthy controls in some of the sleep disorders is not fully
      elucidated. Immunological background in disease development in both multiple
      sclerosis and sleep disorders have been proposed as possible common
      pathophysiological mechanism and recent findings of disrupted melatonin pathways
      in MS patients suggest multi-level causative mechanism of the development of
      sleep disorders in MS. 

PMID- 24321164
TI  - Evaluating the effects of amantadin, modafinil and acetyl-L-carnitine on fatigue
      in multiple sclerosis--result of a pilot randomized, blind study.
AB  - OBJECTIVE: Fatigue affects more than 60% of multiple sclerosis (MS) patients and
      is one of the most troublesome symptoms of the disease. Current treatment options
      for MS fatigue include amantadine, modafinil and acetyl-l-carnitine (ALCAR). The
      aim of our study was to compare efficacy of amantadine, modafinil and ALCAR with
      placebo in patients with MS. METHODS: Patients with MS and a disability level <=
      5.5 on the Kurtzke Expanded Disability Status Scale (EDSS) and fatigue were
      included in the study. Patients were assigned to a one month treatment with
      either amantadine 200mg, ALCAR 2g, modafinil 200mg or placebo. Efficacy of the
      treatment was evaluated by using the modified fatigue impact scale (MFIS).
      RESULTS: Sixty patients were included in the study (39 females). The mean age of
      patients was 38 +/- 6.7 years and the mean disease duration was 6.6 +/- 1.2
      years. Contrast analysis showed significantly lower mean MFIS score after one
      month in patients on amantadine compared to placebo (mean difference=17.3,
      p=0.001). There was also a trend of a lower MFIS score in ALCAR group in
      comparison to placebo (mean difference=12.4, p=0.05, with Keppel-corrected alpha
      of 0.046). The quality of life measured as SF 36 - PCS and SF 36 - MCS proved to
      be significantly influenced by treatment. CONCLUSION: One month treatment with
      amantadine improved fatigue in patients with relapsing-remitting MS as evaluated
      by MFIS. No or only a trend of improvement was seen in patients treated with
      modafinil or ALCAR, respectively.

PMID- 24321165
TI  - Teriflunomide for the treatment of multiple sclerosis.
AB  - Teriflunomide is a new active drug which has recently been approved as a first
      line treatment of relapsing forms of MS in the US, Australia, Argentina, and the
      European Union. It is characterized by a once-daily oral application and a well
      established long-term safety profile. The main therapeutic effect is considered
      to be mediated via the inhibition of the de novo synthesis of pyrimidine in
      proliferating immune cells. Two phase III clinical trials (TEMSO, TOWER) tested
      teriflunomide in patients with relapsing forms of MS: efficacy was shown, with
      positive effects on relapse rates and disease progression for 14 mg/day. Overall,
      the safety profile in these studies was favorable. In patients treated with
      teriflunomide, the regular monitoring of blood cell counts and liver enzymes is
      required. Teriflunomide must not be used during pregnancy. In this article, we
      review recent phase II and phase III clinical trial data, and discuss the
      potential of teriflunomide for the treatment of relapsing forms of MS.

PMID- 24321166
TI  - Development and evaluation of simulation-based fever management module for
      children with febrile convulsion.
AB  - BACKGROUND: A reliable and valid checklist for the evaluation of simulation
      learning outcomes has great value in nursing education. This study focuses on
      simulation-based fever management module including checklist for febrile
      convulsion in pediatric nursing. PURPOSES: This study has two aims; (a) to
      develop a simulation-based fever management module for treating children with
      febrile convulsion, and (b) to evaluate students' performance and satisfaction.
      PARTICIPANTS: A convenient sample of 147 senior nursing students from two nursing
      schools in South Korea participated in this study from April 29 to June 14, 2013.
      METHODS: This study was a three-stage process: developing the simulation-based
      module including algorithm with scenarios, items in checklist, and contents of
      debriefing (Stage I), performing simulation and debriefing for nursing students
      (Stage II), and evaluating the evaluation checklist of simulation performance and
      satisfaction of nursing students (Stage III). Student satisfaction was measured
      using the Satisfaction of Simulations Experience [SSE] scale. Debriefing data
      were analyzed using the Matrix Method. RESULTS: A scenario script was created to
      treat the patient's health issues. The algorithm proceeded as follows:
      identification of patient's condition (Step I), nursing interventions (Step II),
      and outcome evaluation and feedback (Step III). The total mean score of the
      evaluation checklist was 2.67 (+/-.32). The debriefing categories were as
      follows: non-technical skills, self-efficacy, critical thinking, and technical
      skills. The total mean score of the SSE was 4.48 (+/-.42). CONCLUSION: This study
      provides a blueprint for simulation-based practice for both nursing educators and
      nursing students. Further studies of checklists used in different contexts would
      be valuable for expanding upon this research.

PMID- 24321167
TI  - Type III dens fracture with vertical distraction.

PMID- 24321168
TI  - Diffusion tensor imaging of somatosensory tract in cervical spondylotic
      myelopathy and its link with electrophysiological evaluation.
AB  - BACKGROUND AND CONTEXT: Abnormal somatosensory evoked potential (SEP) (ie,
      prolonged latency) has been associated with poor surgical prognosis of cervical
      spondylotic myelopathy (CSM). PURPOSE: To further characterize the extent of
      microstructural damage to the somatosensory tract in CSM patients using diffusion
      tensor imaging (DTI). STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE:
      A total of 40 volunteers (25 healthy subjects and 15 CSM patients). OUTCOME
      MEASURES: Clinical, electrophysiological, and radiological evaluations were
      performed using the modified Japanese Orthopedic Association (mJOA) scoring
      system, SEP, and cord compression ratio in anatomic magnetic resonance (MR)
      images, respectively. Axial diffusion MR images were taken using a pulsed
      gradient, spin-echo-echo-planar imaging sequence with a 3-T MR system. The
      diffusion indices in different regions of the spinal cord were measured. METHODS:
      Comparison of diffusion indices among healthy and myelopathic spinal cord with
      intact and impaired SEP responses were performed using one-way analysis of
      variance. RESULTS: In healthy subjects, fractional anisotropy (FA) values were
      higher in the dorsal (0.73+/-0.11) and lateral columns (0.72+/-0.13) than in the
      ventral column of white matter (0.58+/-0.10) (eg, at C4/5) (p<.05). FA was
      dramatically dropped in the dorsal (0.54+/-0.16) and lateral columns (0.51+/
      0.13) with little change in the ventral column (0.48+/-0.15) at the compressive
      lesions in CSM patients. There were no significant differences in the mJOA scores
      or cord compression ratios between CSM patients with or without abnormal SEP.
      However, patients with abnormal SEP showed an FA decrease in the dorsal column
      cephalic to the lesion (0.56+/-0.06) (ie, at C1/2, compared with healthy subjects
      [0.66+/-0.02]), but the same decrease was not observed for those without a SEP
      abnormality (0.67+/-0.02). CONCLUSION: Spinal tracts were not uniformly affected
      in the myelopathic cervical cord. Changes in diffusion indices could delineate
      focal or extensive myelopathic lesions in CSM, which could account for abnormal
      SEP. DTI analysis of spinal tracts might provide additional information not
      available from conventional diagnostic tools for prognosis of CSM.

PMID- 24321169
TI  - Determination of humeral head size in anatomic shoulder replacement for
      glenohumeral osteoarthritis.
AB  - BACKGROUND: We hypothesized that a sphere mapped to specific preserved
      nonarticular landmarks of the proximal humerus can accurately predict native
      humeral head radius of curvature (ROC) and head height (HH) in the
      osteoarthritic, deformed humeral head. METHODS: Three consistent nonarticular
      landmarks were defined with a 3-dimensional sphere (and 2-dimensional circle in
      midcoronal plane) placed along the articular surface in 31 normal cadaveric
      humeri. Side-to-side differences in ROC and HH were determined in 22 pairs of
      normal shoulders. Using the nonarticular landmarks and sphere method, 3
      independent blinded observers performed 2 sets of measurements in 22 pairs of
      shoulders with unilateral glenohumeral osteoarthritis. The predicted native ROC
      and HH in the pathologic shoulder were compared with the normal side control.
      RESULTS: The mean side-to-side difference in normal shoulders was 0.2 mm (ROC)
      and 0.6 mm (HH). In the unilateral osteoarthritis cases, the intraobserver mean
      differences for the normal side were 0.3 mm (ROC) and 0.9 mm (HH). The pathologic
      side ROC and HH, defined by the sphere, exhibited intraobserver differences of
      0.5 mm (ROC) and 1.0 mm (HH). The mean side-to-side differences between the
      normal and pathologic sides were 0.5 mm (ROC) with concordance correlation
      coefficient of 0.95 and 1.3 mm (HH) with concordance correlation coefficient of
      0.66. CONCLUSION: A sphere mapped to preserved nonarticular bone landmarks can be
      used for accurate preoperative measurement of premorbid humeral head size and
      therefore the selection of an anatomically sized prosthetic head. This is
      applicable postoperatively, as is a circle method for 2-dimensional assessment of
      anatomic humeral reconstruction in the coronal plane.

PMID- 24321170
TI  - Development of a clinician reputation metric to identify appropriate problem
      medication pairs in a crowdsourced knowledge base.
AB  - BACKGROUND: Correlation of data within electronic health records is necessary for
      implementation of various clinical decision support functions, including patient
      summarization. A key type of correlation is linking medications to clinical
      problems; while some databases of problem-medication links are available, they
      are not robust and depend on problems and medications being encoded in particular
      terminologies. Crowdsourcing represents one approach to generating robust
      knowledge bases across a variety of terminologies, but more sophisticated
      approaches are necessary to improve accuracy and reduce manual data review
      requirements. OBJECTIVE: We sought to develop and evaluate a clinician reputation
      metric to facilitate the identification of appropriate problem-medication pairs
      through crowdsourcing without requiring extensive manual review. APPROACH: We
      retrieved medications from our clinical data warehouse that had been prescribed
      and manually linked to one or more problems by clinicians during e-prescribing
      between June 1, 2010 and May 31, 2011. We identified measures likely to be
      associated with the percentage of accurate problem-medication links made by
      clinicians. Using logistic regression, we created a metric for identifying
      clinicians who had made greater than or equal to 95% appropriate links. We
      evaluated the accuracy of the approach by comparing links made by those
      physicians identified as having appropriate links to a previously manually
      validated subset of problem-medication pairs. RESULTS: Of 867 clinicians who
      asserted a total of 237,748 problem-medication links during the study period, 125
      had a reputation metric that predicted the percentage of appropriate links
      greater than or equal to 95%. These clinicians asserted a total of 2464 linked
      problem-medication pairs (983 distinct pairs). Compared to a previously validated
      set of problem-medication pairs, the reputation metric achieved a specificity of
      99.5% and marginally improved the sensitivity of previously described knowledge
      bases. CONCLUSION: A reputation metric may be a valuable measure for identifying
      high quality clinician-entered, crowdsourced data.

PMID- 24321172
TI  - Chance and necessity of simultaneous HBsAg and anti-HBs detection in the serum of
      chronic HBsAg carriers.

PMID- 24321171
TI  - An intervention to improve mental health care for conflict-affected forced
      migrants in low-resource primary care settings: a WHO MhGAP-based pilot study in
      Sri Lanka (COM-GAP study).
AB  - BACKGROUND: Inadequacy in mental health care in low and middle income countries
      has been an important contributor to the rising global burden of disease. The
      treatment gap is salient in resource-poor settings, especially when providing
      care for conflict-affected forced migrant populations. Primary care is often the
      only available service option for the majority of forced migrants, and
      integration of mental health into primary care is a difficult task. The proposed
      pilot study aims to explore the feasibility of integrating mental health care
      into primary care by providing training to primary care practitioners serving
      displaced populations, in order to improve identification, treatment, and
      referral of patients with common mental disorders via the World Health
      Organization Mental Health Gap Action Programme (mhGAP). METHODS/DESIGN: This
      pilot randomized controlled trial will recruit 86 primary care practitioners
      (PCP) serving in the Puttalam and Mannar districts of Sri Lanka (with displaced
      and returning conflict-affected populations). The intervention arm will receive a
      structured training program based on the mhGAP intervention guide. Primary
      outcomes will be rates of correct identification, adequate management based on
      set criteria, and correct referrals of common mental disorders. A qualitative
      study exploring the attitudes, views, and perspectives of PCP on integrating
      mental health and primary care will be nested within the pilot study. An economic
      evaluation will be carried out by gathering service utilization information.
      DISCUSSION: In post-conflict Sri Lanka, an important need exists to provide
      adequate mental health care to conflict-affected internally displaced persons who
      are returning to their areas of origin after prolonged displacement. The proposed
      study will act as a local demonstration project, exploring the feasibility of
      formulating a larger-scale intervention study in the future, and is envisaged to
      provide information on engaging PCP, and data on training and evaluation
      including economic costs, patient recruitment, and acceptance and follow-up
      rates. The study should provide important information on the WHO mhGAP
      intervention guide to add to the growing evidence base of its implementation.
      TRIAL REGISTRATION: SLCTR/2013/025.

PMID- 24321174
TI  - Characterization of the peripheral blood transcriptome in a repeated measures
      design using a panel of healthy individuals.
AB  - A repeated measures microarray design with 22 healthy, non-smoking volunteers
      (aging 32+/-5years) was set up to study transcriptome profiles in whole blood
      samples. The results indicate that repeatable data can be obtained with high
      within-subject correlation. Probes that could discriminate between individuals
      are associated with immune and inflammatory functions. When investigating
      possible time trends in the microarray data, we have found no differential
      expression within a sampling period (within-season effect). Differential
      expression was observed between sampling seasons and the data suggest a weak
      response of genes related to immune system functioning. Finally, a high number of
      probes showed significant season-specific expression variability within subjects.
      Expression variability increased in springtime and there was an association of
      the probe list with immune system functioning. Our study suggests that the blood
      transcriptome of healthy individuals is reproducible over a time period of
      several months. 

PMID- 24321173
TI  - Combined genomic expressions as a diagnostic factor for oral squamous cell
      carcinoma.
AB  - Trends in genetics are transforming in order to identify differential
      coexpressions of correlated gene expression rather than the significant
      individual gene. Moreover, it is known that a combined biomarker pattern improves
      the discrimination of a specific cancer. The identification of the combined
      biomarker is also necessary for the early detection of invasive oral squamous
      cell carcinoma (OSCC). To identify the combined biomarker that could improve the
      discrimination of OSCC, we explored an appropriate number of genes in a combined
      gene set in order to attain the highest level of accuracy. After detecting a
      significant gene set, including the pre-defined number of genes, a combined
      expression was identified using the weights of genes in a gene set. We used the
      Principal Component Analysis (PCA) for the weight calculation. In this process,
      we used three public microarray datasets. One dataset was used for identifying
      the combined biomarker, and the other two datasets were used for validation. The
      discrimination accuracy was measured by the out-of-bag (OOB) error. There was no
      relation between the significance and the discrimination accuracy in each
      individual gene. The identified gene set included both significant and
      insignificant genes. One of the most significant gene sets in the classification
      of normal and OSCC included MMP1, SOCS3 and ACOX1. Furthermore, in the case of
      oral dysplasia and OSCC discrimination, two combined biomarkers were identified.
      The combined expression revealed good performance in the validation datasets. The
      combined genomic expression achieved better performance in the discrimination of
      different conditions than a single significant gene. Therefore, it could be
      expected that accurate diagnosis for cancer could be possible with a combined
      biomarker. 

PMID- 24321175
TI  - Community-acquired diarrhea among children and adults in urban settings in
      Senegal: clinical, epidemiological and microbiological aspects.
AB  - BACKGROUND: Only limited data are available relating to the etiology of diarrhea
      in children and adults in Senegal. The aim of this prospective study was to
      describe the epidemiology and etiology of community-acquired diarrheal infections
      in children and adults living in urban settings. METHODS: A prospective study was
      carried out from March 2009 to December 2010, in the urban region of Dakar,
      Senegal. Patients with acute diarrhea were enrolled, interviewed to collect their
      clinical history, and their stools were tested for bacteria, virus and parasites.
      RESULTS: A total of 223 patients (including 112 children younger than five years
      old) with diarrhea were included. At least one enteropathogen was detected in 81%
      (180/223) of the patients: 29% (64/223) had bacterial infections (mainly
      diarrheagenic E. coli and Shigella spp), 21% (39/185) viral infections (mainly
      rotavirus) and 14% (31/223) parasitic infections. Co-infection was identified in
      17.8% (32/180) of the patients. Viral infection was significantly more frequent
      in children under five years old during the dry season. Bacteria and parasites
      were equally frequent in all age groups. There was a seasonal variation of
      bacterial infections during the study period, with a higher proportion of
      infections being bacterial, and due to Salmonella spp. in particular, during the
      rainy season. CONCLUSION: Our study suggests that in urban settings in Senegal,
      rotavirus is the principal cause of pediatric diarrhea during the dry season and
      that the proportion of bacterial infections seems to be higher during the rainy
      season. Further work is needed to document the burden of diarrheal diseases in
      sub-Saharan urban communities and to identify risk factors, including those
      linked to the rapid and unplanned urbanization in Africa.

PMID- 24321176
TI  - Seasonal variation in the degu (Octodon degus) endocrine stress response.
AB  - Many wild animals show seasonal variation in circulating levels of stress
      hormones. Seasonal changes in the stress response may help animals better cope
      with the different challenges faced during each life history stage. We determined
      the seasonal stress profile of wild, free-living degus in Chile. Female degus
      were sampled during non-breeding (January), mating/early gestation (July), late
      gestation (August), and lactation (1st litter-September, 2nd litter-January).
      Male degus were sampled during the first three time-points. We measured baseline
      cortisol (CORT), stress-induced CORT, and negative feedback efficacy using a
      dexamethasone suppression test. While we found that neither males nor females
      showed seasonal variation in baseline CORT or negative feedback levels, we did
      find significant seasonal variation in stress-induced CORT levels of both sexes.
      Male stress-induced CORT was lowest during mating while female stress-induced
      CORT was highest during late gestation and lactation. Overall, females had higher
      stress-induced CORT compared to males. Our data suggest that stress-induced
      levels of CORT are highest during periods with increased chance of stressor
      exposure or times of positive energy balance. Consequently, CORT responses to
      stress appear to be regulated according to different life history needs. 

PMID- 24321177
TI  - Thyroid hormone concentrations in relation to age, sex, pregnancy, and perinatal
      loss in bottlenose dolphins (Tursiops truncatus).
AB  - This study evaluated circulating concentrations of thyroid hormones in relation
      to age, sex, pregnancy status, and perinatal loss in bottlenose dolphins
      (Tursiops truncatus) under human care. A total of 373 blood samples were
      collected from 60 individual dolphins housed at nine aquariums/oceanariums. Serum
      concentrations of total and free thyroxine (T4) and triiodothyronine (T3) were
      analyzed with commercial RIA kits validated for use with dolphins. While the
      effect of age was indicated by higher (P<0.0001) concentrations of total and free
      T4 and T3 in juveniles than adults, the effect of sex on thyroid hormones was
      inconclusive. The effect of pregnancy was indicated by higher (P<0.035) total and
      free T4 and T3 during early pregnancy compared to non-pregnancy. For both
      successful and unsuccessful pregnancy outcomes, maternal concentrations of
      thyroid hormones were highest during early, intermediate during mid, and lowest
      during late pregnancy (P<0.07 to P<0.0001). Compared to live and thriving births,
      concentrations of total and free T4 and total T3 were lower (P<0.08 to P<0.001)
      in dolphins with perinatal loss. Lower concentrations ranged from 10% to 14%
      during early, 11% to 18% during mid, and 23% to 37% during late pregnancy. In
      conclusion, the effects of age, reproductive status and stage of pregnancy on
      thyroid hormone concentrations are necessary factors to take into account when
      assessing thyroid gland function. Since perinatal loss may be associated with
      hypothyroidism in dolphins, analysis of serum T4 and T3 should be considered for
      those dolphins that have a history of pregnancy loss. 

PMID- 24321178
TI  - Growth and endocrine effect of growth hormone transgene dosage in diploid and
      triploid coho salmon.
AB  - Growth-hormone transgene dosage, polyploidy, and parental effects on growth and
      endocrine responses have been assessed in coho salmon. Diploid fry with one or
      two transgene doses grew equally, whereas later-stage juvenile homozygotes grew
      faster than hemizygotes. In contrast, homozygotes and hemizygotes grew equally
      after smoltification, both in sea water and fresh water. Triploid transgenic
      salmon showed impaired growth which could not be fully overcome with additional
      transgene copies. Levels of muscle GH mRNA were elevated in two vs. one transgene
      dose diploids, but in triploids, a dosage effect was observed in muscle but not
      for animals carrying three transgene doses. IGF-I mRNA levels were elevated in
      transgenic vs. non-transgenic animals, but a dosage effect was not observed.
      Diploids and triploids with two transgenes had higher plasma GH levels than one
      dose animals, but three-dose triploids showed no further elevation. Circulating
      IGF-I levels also showed a dosage effect in diploids, but not among any transgene
      doses in triploids. The present study reveals complex interactions among
      transgene dosage, maternal effects, developmental stage, and ploidy on growth and
      endocrine parameters in GH transgenic coho salmon. Specifically, GH transgenes do
      not always express nor have effects on growth that are directly correlated with
      the number of transgenes. Further, the reduced growth rate seen in triploid
      transgenic animals could not be fully overcome by increasing transgene dosage.
      The findings have relevance for understanding growth physiology, transgene
      function, and for environmental risk assessments that require understanding
      phenotypes of hemizygous vs. homozygous transgenic animals in populations. 

PMID- 24321179
TI  - Tilapia male urinary pheromone stimulates female reproductive axis.
AB  - Mozambique tilapia males congregate in leks where they establish dominance
      hierarchies and attract females to spawn in sandy pits. Dominant males store more
      urine than subordinates and the pattern of urination and the high sensitivity of
      females to male urine suggest chemical signalling via the urine. Here we show
      that pre-ovulated and post-spawn females when exposed to dominant male urine
      increased significantly, in less than 1h, the release rate of the maturation
      inducing steroid 17,20beta-dihydroxypregn-4-en-3-one which is maintained elevated
      for at least 6h. This indicates a pheromonal role for male urine in the
      synchronisation of spawning. Furthermore, we show that the lack of affinity of
      17,20betaP to sex steroid binding globulin explains, at least partly, its rapid
      release and lack of detection in the blood. Thus tilapia urine involvement in
      several communication processes confirms that cichlids have evolved a
      sophisticated chemical signalling system together with their complex visual,
      acoustic and behavioural displays. 

PMID- 24321180
TI  - Unmarried male migrants and sexual risk behavior: a cross-sectional study in
      Shanghai, China.
AB  - BACKGROUND: In China, there is increasing concern because of the rapid increase
      in HIV infection recorded over recent years. Migrant workers are recognized as
      one of the groups most affected. In this study, HIV/AIDS-related knowledge,
      attitudes, and behavior among unmarried migrant workers in Shanghai are
      investigated, with the aim of providing critical information for policy makers
      and sex educators to reinforce sexual health services and sex health education
      targeting the behavior and sexual health of unmarried male migrants. METHODS: A
      cross-sectional survey was conducted among unmarried male migrant workers in
      Shanghai, China's largest city and housing the most migrants. A self
      administered, anonymous questionnaire was used to collect information on
      knowledge, attitudes, and behavior associated with increased risk of HIV/AIDS.
      RESULTS: A total of 2254 subjects were questioned, with a response rate of 91.3%.
      Among those interviewed, 63.5% reported sexual activities. Misconceptions
      regarding HIV transmission, poor perception of HIV infection, and low use of
      condoms were not uncommon. Among those who had sexual intercourse, 73.7% had not
      used condoms in their last sexual intercourse, and 28.6% reported having engaged
      in sexual risk behavior (defined as having at least one non-regular partner).
      Multivariate logistic regression analyses identified several indicators of sexual
      risk behavior, including younger age at first sexual intercourse (OR: 0.67, 95%
      CI: 0.31-0.91 for older age at first sexual intercourse), more cities of
      migration (OR: 2.91, 95% CI: 2.17-3.81 for high level; OR: 1.15, 95% CI: 1.06
      1.29 for medium level), poor perception of acquiring HIV/AIDS (OR: 1.52, 95% CI:
      1.33-1.96 for unlikely; OR: 2.38, 95% CI: 1.61-3.70 for impossible), frequent
      exposure to pornography (OR: 0.33, 95% CI: 0.11-0.43 for never; OR: 0.69, 95% CI:
      0.60-1.81 for less frequently), not knowing someone who had or had died of
      HIV/AIDS and related diseases (OR: 2.13, 95% CI: 1.70-2.53 for no), and having
      peers who engaged in sex with a non-regular sex partner (OR: 4.40, 95% CI: 3.37
      5.56 for yes). CONCLUSIONS: Today, it is necessary to reinforce sex health
      education among unmarried migrants and sexual health services should target
      vulnerable migrant young people.

PMID- 24321181
TI  - A comparative study of extraction techniques for maximum recovery of glutamate
      decarboxylase (GAD) from Aspergillus oryzae NSK.
AB  - BACKGROUND: gamma-Amino butyric acid (GABA) is a major inhibitory
      neurotransmitter of the mammalian central nervous system that plays a vital role
      in regulating vital neurological functions. The enzyme responsible for producing
      GABA is glutamate decarboxylase (GAD), an intracellular enzyme that both food and
      pharmaceutical industries are currently using as the major catalyst in trial
      biotransformation process of GABA. We have successfully isolated a novel strain
      of Aspergillus oryzae NSK that possesses a relatively high GABA biosynthesizing
      capability compared to other reported GABA-producing fungal strains, indicating
      the presence of an active GAD. This finding has prompted us to explore an
      effective method to recover maximum amount of GAD for further studies on the
      GAD's biochemical and kinetic properties. The extraction techniques examined were
      enzymatic lysis, chemical permeabilization, and mechanical disruption. Under the
      GAD activity assay used, one unit of GAD activity is expressed as 1 MUmol of GABA
      produced per min per ml enzyme extract (U/ml) while the specific activity was
      expressed as U/mg protein. RESULTS: Mechanical disruption by sonication, which
      yielded 1.99 U/mg of GAD, was by far the most effective cell disintegration
      method compared with the other extraction procedures examined. In contrast, the
      second most effective method, freeze grinding followed by 10% v/v toluene
      permeabilization at 25 degrees C for 120 min, yielded only 1.17 U/mg of GAD,
      which is 170% lower than the sonication method. Optimized enzymatic lysis with 3
      mg/ml Yatalase(r) at 60 degrees C for 30 min was the least effective. It yielded
      only 0.70 U/mg of GAD. Extraction using sonication was further optimized using a
      one-variable-at-a-time approach (OVAT). Results obtained show that the yield of
      GAD increased 176% from 1.99 U/mg to 3.50 U/mg. CONCLUSION: Of the techniques
      used to extract GAD from A. oryzae NSK, sonication was found to be the best.
      Under optimized conditions, about 176% of GAD was recovered compared to recovery
      under non optimized conditions. The high production level of GAD in this strain
      offers an opportunity to conduct further studies on GABA production at a larger
      scale.

PMID- 24321182
TI  - Improving ascertainment and communication of prognosis in intracerebral
      hemorrhage.
AB  - Prognostication after intracerebral hemorrhage remains a significant challenge
      for the field of neurocritical care. Despite several available tools that can
      predict mortality and, to some degree, functional outcomes, deciding which
      prediction score to use and how best to translate the resultant population-based
      value to the individual level is not always clear. As more and more scores are
      published, we need to give due attention to the qualitative aspect of
      prognostication and explore how best to move this critical aspect of our field
      forward. 

PMID- 24321183
TI  - Effects of atorvastatin on biomarkers of inflammation in chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with inflammation. The
      effects of atorvastatin on biomarkers of inflammation were assessed in CKD
      patients in the LORD trial. METHODS: 117 patients with serum creatinine >120
      MUmol/L were randomized to receive atorvastatin 10 mg/day (56) or placebo (61)
      and followed for a mean of 2.5 years. 33 individuals with normal kidney function
      were controls. Outcomes included comparison of changes in pentraxin-3 (PTX3), TNF
      alpha, CRP, IL-6, IL-8, and IL-10 between atorvastatin and placebo-treated
      patients. RESULTS: At baseline, compared with controls, CKD patients had
      increased PTX3 (mean, 1.08 vs. 0.58 ng/mL; p < 0.001), CRP (4.9 vs. 1.5 mg/L; p <
      0.001), IL-8 (6.00 vs. 4.58 pg/mL; p = 0.001), IL-10 (59.0 vs. 17.6 pg/mL; p =
      0.007), and TNF-alpha (18.0 vs. 5.6 ng/mL; p < 0.001). In patients with raised
      baseline plasma IL-6/8/10 and/or PTX3 the eGFR decline during the trial was
      significantly less in those treated with atorvastatin compared to placebo (mean
      change, -3.36; vs. + 1.25 mL/min/1.73 m2/year; difference, 4.61 95% CI 0.98 -
      8.25; p = 0.002), whilst those without raised inflammatory biomarkers showed no
      difference. Placebo treated patients with raised TNF-alpha levels had no eGFR
      decline (p > 0.90), whereas in atorvastatin-treated patients eGFR declined (p =
      0.05). CONCLUSIONS: CKD patients with inflammation treated with atorvastatin had
      significantly less eGFR decline. Larger studies using statin therapy,
      specifically enrolling CKD patients with inflammation, may be worthwhile
      exploring.

PMID- 24321184
TI  - The impact of glucose load on left ventricular mass in peritoneal dialysis
      patients.
AB  - BACKGROUND: Cardiovascular (CV) complications are the main cause of morbidity and
      mortality in peritoneal dialysis (PD) patients. Left ventricular hypertrophy
      (LVH) is a well-known major CV risk factor. AIM: To evaluate the impact of
      peritoneal glucose load on left ventricular mass (LVM) in PD patients. METHODS:
      In this cross sectional study the glucose load and LVM were evaluated in 43
      stable patients on maintenance PD for 24 - 78 months. Glucose load was calculated
      using a unique peritoneal glucose load index (PGLI) referred to g/kg/day glucose
      given in the daily PD prescription. LVM index (LVMI) was calculated using the
      Devereux et al. formula. RESULTS: The PGLI was positively correlated with HbA1c
      and LVMI (p < 0.001). Patients with PGLI > 3 g/kg/day had higher HbA1c and LVMI
      compared to those with PGLI <= 3 g/kg/day (p < 0.001). CONCLUSIONS: Higher PGLI
      values were associated with worse glycemic control and increased LVMI. Efforts
      should be made to minimize the PGL. All other risk factors that may contribute to
      the development of LVH in PD patients should be identified and treated.
      Additional multicenter, randomized control trials are needed to determine the
      target objectives of PGLI.

PMID- 24321185
TI  - Low sensitivity of the exit site scoring system in detecting exit site infections
      in peritoneal dialysis patients.
AB  - INTRODUCTION: To evaluate the utility of the exit site scoring system in
      diagnosing exit site infections, we compared its scores to the well established
      exit site categories outlined by Twardowski and Prowant. METHODS: We examined the
      exit sites of 50 patients on peritoneal dialysis. Each exit site was given a
      score ranging from "zero" to ">= 4" according to the exit site scoring system.
      Exit sites were simultaneously classified into one of the exit site diagnostic
      categories outlined by Twardowski and Prowant. The sensitivity and specifity of
      the exit site scoring system in diagnosing exit site infection was then
      calculated in reference to the exit sites classified as infected according to
      Twardowski criteria. RESULTS: The proportions of perfect, good, equivocal, and
      infected exit sites were 24%, 22%, 32%, and 22%, respectively. 21 exit sites had
      an exit site score of zero. Of those, 12 (57.1%) were perfect, 7 (33.3%) were
      good, 1 (4.8%) was equivocal, and 1 (4.8%) was actually infected. 21 exit sites
      had an exit site score ranging from 1 to 3 without purulent discharge. Of those,
      4 (18.2%) were good, 15 (68.2%) were equivocal, and 3 (13.6%) were infected. The
      specifity of the exit site scoring system in diagnosing exit site infection was
      100%, but its sensitivity was only 63.6%. CONCLUSION: The exit site scoring
      system is not a sensitive tool for diagnosing exit site infection mainly because
      it ignores evaluation of the sinus for granulation tissue. Exuberant granulation
      tissue in the sinus tract is not always accompanied by purulent drainage.

PMID- 24321186
TI  - Lipopolysaccharide in ovarian follicular fluid influences the steroid production
      in large follicles of dairy cows.
AB  - In postpartum dairy cows, various inflammatory diseases depress reproductive
      performance. Lipopolysaccharide (LPS) derived from infections of the uterus or
      mammary gland with Gram-negative bacteria was shown to suppress steroid
      production in the granulosa cells of follicles in vitro. The aim of the study was
      to investigate the relationship between LPS in ovarian follicular fluid and
      steroidogenesis by the theca and granulosa cells of the large follicles in vivo.
      Bovine ovaries were collected from a slaughterhouse, and the largest (F1) and the
      second largest (F2) follicles were used (>8 mm in diameter, n=38). LPS
      concentration in the follicular fluid was measured using quantitative kinetic
      assay. Follicular steroidogenesis was evaluated by measuring the estradiol (E2)
      and progesterone (P4) concentration in follicular fluid and by analysing
      transcription levels of steroidogenesis-related genes in theca and granulosa
      cells. LPS concentration detected in follicular fluid ranged from 0.2 to 2.0
      EU/mL. In follicles with a high level of LPS (>0.5 EU/mL, n=15), the
      concentration of E2 was lower and that of P4 was higher when compared to those in
      follicles with a low level of LPS (<0.5 EU/mL, n=23), which was observed both in
      F1 and F2 follicles. Furthermore, in follicles with a high level of LPS,
      transcripts of steroidogenic enzymes such as CYP17 and P450arom were lower. In
      those follicles, the expression of caspase-3 was high, suggesting an association
      with follicular atresia. These findings indicate that LPS present in follicular
      fluid may cause ovarian dysfunction by inhibiting follicular activity.

PMID- 24321187
TI  - A multicentre clinical study on the injection of ceftriaxone/sulbactam compared
      with cefoperazone/sulbactam in the treatment of respiratory and urinary tract
      infections.
AB  - OBJECTIVE: This clinical study was designed to evaluate the efficacy and safety
      of this therapy in the treatment of respiratory and urinary infections caused by
      ceftriaxone-resistant bacteria in comparison with the effect of
      cefoperazone/sulbactam on cefoperazone-resistant bacteria. METHODS: A total of
      285 patients aged from 18 to 65 years old, with a respiratory or urinary tract
      bacterial infection, were enrolled into this multicentre, open-label, controlled
      clinical study, and bacteria that were either ceftriaxone-resistant or
      cefoperazone-resistant were isolated from the patients, whose condition had not
      improved after three days of treatment with ceftriaxone or cefoperazone. To be
      selected for the study, bacterial cultures obtained from the patients had to be
      positive before enrolment, and all of the isolates were required to be beta
      lactamase-positive. Of these patients, 253 completed the trial, and 263 were
      enrolled into the intention-to-treat (ITT) analysis. All of the 285 patients were
      included in the safety analysis. RESULTS: The cure and effective rates were
      39.55% and 85.07% in the ceftriaxone/sulbactam group and 36.43% and 79.84% in the
      cefoperazone/sulbactam group; the bacterial eradication rates were 83.58% and
      83.72%; and the adverse-event rates were 7.48% and 7.80%, respectively. There
      were no significant differences between the two groups (p > 0.05). CONCLUSION:
      Ceftriaxone/sulbactam is as effective and well-tolerated as
      cefoperazone/sulbactam for the treatment of intermediate and severe bacterial
      infections caused by resistant strains.

PMID- 24321188
TI  - Energy and protein intakes of hospitalised patients with acute respiratory
      failure receiving non-invasive ventilation.
AB  - BACKGROUND & AIM: Nutritional intake of patients in acute respiratory failure
      receiving non-invasive ventilation has not previously been described, and no
      protocols have been developed to guide practice to optimise nutritional status.
      We aimed to measure energy and protein intakes of patients in acute respiratory
      failure requiring non-invasive ventilation receiving standard hospital
      nutritional care. METHODS: Food and fluid intake forms were completed by nursing
      staff for all meals and mid meals for patients admitted with respiratory failure
      commencing on non-invasive ventilation. Intake was converted from quartiles of
      food consumed into energy and protein to enable comparison with estimated daily
      requirements using descriptive statistics. Multinomial stepwise regression
      analysis was used to determine factors associated with inadequate protein and
      energy intake. RESULTS: Over 283 total days of intake, 36 participants (67%
      female, aged 65 +/- 9 years) achieved on average 1434 +/- 627 kcal and 63 +/- 29
      g protein daily. Overall, 28 patients (78%, 95% CI: 61-90%) met less than 80% of
      estimated energy requirements and 27 patients (75%, 95% CI: 58-88%) met less than
      80% of estimated protein requirements. Being fed orally, longer time on non
      invasive ventilation and higher BMI were associated with poorer intakes. Better
      nutritional status on admission and measuring intake closer to hospital discharge
      was associated with improved intakes. CONCLUSION: Patients with acute respiratory
      failure requiring non-invasive ventilation often had inadequate oral intake,
      particularly with increasing time on non-invasive ventilation, and earlier during
      their hospital admission. Development of protocols to optimise nutritional intake
      for these patients may improve outcomes and reduce regular readmission rates.

PMID- 24321190
TI  - Reassessment of the current American Joint Committee on Cancer staging system for
      pancreatic neuroendocrine tumors.
AB  - BACKGROUND: Adopting a unified staging system for pancreatic neuroendocrine
      tumors (PNETs) has been challenging. Currently, the American Joint Committee on
      Cancer (AJCC) recommends use of the pancreatic adenocarcinoma staging system for
      PNETs. We sought to explore the prognostic usefulness of the pancreatic
      adenocarcinoma staging system for PNETs. STUDY DESIGN: The Surveillance,
      Epidemiology, and End Results program data were used to identify patients with
      PNETs who underwent curative-intent surgical resection from 1983 to 2008. The
      discriminatory ability of the AJCC system was examined and a new TNM system was
      devised using extent of disease variables. RESULTS: In 1,202 patients identified,
      lymph node metastasis was associated with worse 10-year overall survival after
      resection (51% vs 63%; p < 0.0001), as was the presence of distant metastatic
      disease (35% vs 62%; p < 0.0001). The current AJCC system (recorded by the
      Surveillance, Epidemiology, and End Results program in 412 patients since 2004)
      distinguished 5-year overall survival only between stages I and II (p = 0.01),
      but not between stages II and III (p = 0.97), or stages III and IV (p = 0.36). By
      modifying the T stage to be based on size alone (0.1 to 1.0 cm, 1.1 to 2.0 cm,
      2.1 to 4.0 cm, and >4.0 cm) and revising the TNM subgroups, we propose a novel
      TNM system with improved discriminatory ability between disease stages (stages I
      vs II; p = 0.16; II vs III; p < 0.0001; and III vs IV; p = 0.008). CONCLUSIONS:
      In this study evaluating the current AJCC staging system for PNETs, there were no
      significant differences detected between stages II and III or stages III and IV.
      We propose a novel TNM system that might better discriminate between outcomes
      after surgical resection of PNETs.

PMID- 24321189
TI  - Enhanced angiotensin-converting enzyme activity and systemic reactivity to
      angiotensin II in normotensive rats exposed to a high-sodium diet.
AB  - A high salt diet is associated with reduced activity of the renin-angiotensin
      aldosterone system (RAAS). However, normotensive rats exposed to high sodium do
      not show changes in systemic arterial pressure. We hypothesized that, despite the
      reduced circulating amounts of angiotensin II induced by a high salt diet, the
      cardiovascular system's reactivity to angiotensin II is increased in vivo,
      contributing to maintain arterial pressure at normal levels. Male Wistar rats
      received chow containing 0.27% (control), 2%, 4%, or 8% NaCl for six weeks. The
      high-sodium diet did not lead to changes in arterial pressure, although plasma
      levels of angiotensin II and aldosterone were reduced in the 4% and 8% NaCl
      groups. The 4% and 8% NaCl groups showed enhanced pressor responses to
      angiotensin I and II, accompanied by unchanged and increased angiotensin
      converting enzyme activity, respectively. The 4% NaCl group showed increased
      expression of angiotensin II type 1 receptors and reduced expression of
      angiotensin II type 2 receptors in the aorta. In addition, the hypotensive effect
      of losartan was reduced in both 4% and 8% NaCl groups. In conclusion these
      results explain, at least in part, why the systemic arterial pressure is
      maintained at normal levels in non-salt sensitive and healthy rats exposed to a
      high salt diet, when the functionality of RAAS appears to be blunted, as well as
      suggest that angiotensin II has a crucial role in the vascular dysfunction
      associated with high salt intake, even in the absence of hypertension. 

PMID- 24321191
TI  - Thyroid volume, goiter prevalence, and selenium levels in an iodine-sufficient
      area: a cross-sectional study.
AB  - BACKGROUND: Selenium (Se) is a necessary element for the biosynthesis of thyroid
      hormones. We investigated the relationship between selenium status, thyroid
      volume, and goiter in a cross-sectional study in an iodine-sufficient area.
      METHODS: We selected residents of Chengdu (over 18 years old and living in the
      city for more than 5 years) using a stratified cluster sampling technique.
      Fifteen hundred subjects were selected for the study, which involved a
      questionnaire survey, physical examination, thyroid ultrasound, serum thyroid
      function test, and determination of serum selenium level. Thyroid volume was
      calculated from the thickness, width, length, and a corrective factor for each
      lobe. Ultimately, 1,205 subjects completed the investigation and were included in
      our study. Additionally, 80 school-age children were selected to provide urine
      samples for urinary iodine analysis. We analyzed the data using appropriate
      nonparametric and parametric statistical tests. RESULTS: The median urinary
      iodine value was 184 MUg/L in school-age children, indicating iodine sufficiency.
      The median serum selenium level of the 1,205 subjects was 52.63 (interquartile
      range [IQR] : 40.40-67.00) MUg/L. The median thyroid volume was 9.93 (IQR: 7.71
      12.57) mL; both log-transformed serum selenium and log-transformed thyroid volume
      were Gaussian distributions (P = .638 and P = .046, respectively). The
      prevalences of goiter and thyroid nodules were 8.8% and 18.6%. The prevalences of
      positive thyroid autoantibodies, thyroperoxidase autoantibodies and thyroglobulin
      autoantibodies were 16.7%, 12.0%, and 11.1%, respectively. In the general linear
      regression model, there were positive associations between serum selenium and
      age, and body mass index. We found no association between serum selenium and
      thyroid-stimulating hormone. In simple linear regression analyses, we found no
      association between thyroid volume and serum selenium. There were no significant
      differences in serum selenium between persons with or without goiter. Serum
      selenium was not a risk factor for goiter. CONCLUSION: In our study population,
      serum selenium was neither associated with thyroid volume nor with goiter in an
      iodine-sufficient area. More studies should be conducted by following non
      goitrous persons over time and monitoring their selenium status.

PMID- 24321193
TI  - Nonagenarians: questions and answers. Reply.

PMID- 24321192
TI  - Early loading of hydrophilic titanium implants inserted in low-mineralized (D3
      and D4) bone: one year results of a prospective clinical trial.
AB  - INTRODUCTION: Pure titanium is the material of choice for contemporary dental
      implants. However, superficial reaction of the moderately rough titanium surface
      with atmospheric components decreases its hydrophilicity. INICELL(r) represents a
      chemical alteration and hydrophilization of a moderately rough i. e. sand-blasted
      and acid-etched titanium surface. The hydrophilicity leads to a more homogenous
      adsorption of proteins on the implant surface in-vitro, supporting the activation
      of a higher number of platelets and the generation of a homogenous, complete
      fibrin matrix in the early phases of osseointegration. This in turn helps to
      reduce the healing time and enhances the predictability of osseointegration in
      compromised bony situations.The objective of this case series trial was therefore
      to investigate if early loading (after 8 weeks) of hydrophilic INICELL implants
      is feasible in patients with reduced bone quality. METHODS: In 10 patients, 35
      hydrophilic implants were placed in sites revealing bone quality class 3 and 4,
      and uncovered after 4 weeks. Eight weeks later implants were released for loading
      if the tactile resistance was >=35 Ncm. Lower resistances resulted in 12 weeks
      initial healing period. Insertion torque, ISQ, tactile resistance and vertical
      bone level were evaluated at implant installation, after 4 weeks (uncovering), 8
      or 12 weeks (loading), and 12 weeks and one year after loading. RESULTS: Mean
      implant insertion torque was 21 Ncm. 31 (88.6%) showed a tactile resistance of
      >35 Ncm after eight weeks and were released for prosthetic loading. Eight weeks
      after insertion, one implant (2.9%) had to be removed following a soft tissue
      complication. One implant had to be removed after 4 weeks due to a technical
      complication (fractured Osstell-abutment), it was therefore excluded from the
      analysis.33 of 34 implants (97%) were loaded to occlusion and were in
      situ/functional one year after implantation. ISQs increased from 43 at baseline
      to 63 at eight weeks, and 72 at three months after loading. Then, ISQ remained
      constant until one year after loading. CONCLUSIONS: Within the limitations of
      this prospective case series, hydrophilic implants may allow for shortening of
      the initial healing period even in bone with compromised density.

PMID- 24321194
TI  - A novel CLDN16 mutation in a large family with familial hypomagnesaemia with
      hypercalciuria and nephrocalcinosis.
AB  - BACKGROUND: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is
      a rare tubulopathy leading to renal calcification and progressive renal failure.
      CASE PRESENTATION: We report a consanguineous Arab family (of Qatari origin) with
      7 affected siblings with variable phenotypes including hypomagnesaemia,
      hypercalciuria, nephrocalcinosis and renal stones. Presenting features included
      haematuria and recurrent urinary tract infections. As the biochemical and
      clinical phenotypes of this family resembled familial hypomagnesaemia with
      hypercalciuria and nephrocalcinosis, we performed genetic investigation in order
      to provide a precise molecular diagnosis. We screened all coding regions of the
      CLDN16 gene and identified a novel mutation (c.G647A, p.R216H) which was found
      homozygously in the six severely affected cases, who manifested significant
      nephrocalcinosis, often nephrolithiasis and sometimes reduced GFR. Parents were
      both heterozygous for the mutation and, together with children carrying the
      mutation in its heterozygous state, exhibited mild or no biochemical phenotypes.
      CONCLUSION: Mutations in CLDN16 underlie familial hypomagnesaemia with
      hypercalciuria and nephrocalcinosis but remain a rare cause of nephrocalcinosis
      and nephrolithiasis. Management includes reduction of hypercalciuria with
      thiazide diuretics, correction of serum magnesium and close monitoring of renal
      function given the significant risk of end stage renal failure with this
      inherited form of nephrocalcinosis.

PMID- 24321196
TI  - PPAR-gamma activation limits angiotensin II-mediated atrial remodeling: one drug
      fits all AF patients?

PMID- 24321195
TI  - Fibroblasts in myocardial infarction: a role in inflammation and repair.
AB  - Fibroblasts do not only serve as matrix-producing reparative cells, but exhibit a
      wide range of functions in inflammatory and immune responses, angiogenesis and
      neoplasia. The adult mammalian myocardium contains abundant fibroblasts enmeshed
      within the interstitial and perivascular extracellular matrix. The current review
      manuscript discusses the dynamic phenotypic and functional alterations of cardiac
      fibroblasts following myocardial infarction. Extensive necrosis of cardiomyocytes
      in the infarcted heart triggers an intense inflammatory reaction. In the early
      stages of infarct healing, fibroblasts become pro-inflammatory cells, activating
      the inflammasome and producing cytokines, chemokines and proteases. Pro
      inflammatory cytokines (such as Interleukin-1) delay myofibroblast
      transformation, until the wound is cleared from dead cells and matrix debris.
      Resolution of the inflammatory infiltrate is associated with fibroblast
      migration, proliferation, matrix protein synthesis and myofibroblast conversion.
      Growth factors and matricellular proteins play an important role in myofibroblast
      activation during the proliferative phase of healing. Formation of a mature cross
      linked scar is associated with clearance of fibroblasts, as poorly-understood
      inhibitory signals restrain the fibrotic response. However, in the non-infarcted
      remodeling myocardium, local fibroblasts may remain activated in response to
      volume and pressure overload and may promote interstitial fibrosis. Considering
      their abundance, their crucial role in cardiac inflammation and repair, and their
      involvement in myocardial dysfunction and arrhythmogenesis, cardiac fibroblasts
      may be key therapeutic targets in cardiac remodeling. This article is part of a
      Special Issue entitled Myocyte-Fibroblast Signalling in Myocardium. 

PMID- 24321197
TI  - Prose reading in neglect.
AB  - Prose reading has been shown to be a very sensitive measure of Unilateral Spatial
      Neglect. However, little is known about the relationship between prose reading
      and other measures of neglect and its severity, or between prose reading and
      single word reading. Thirty participants with a first stroke in the right
      hemisphere and clear symptoms of spatial neglect in everyday life were assessed
      with tests of prose reading (text in one column book-like, and in two columns
      magazine-like), single words reading, and a battery of 13 tests investigating
      neglect. Seventy percent of these participants omitted words at the beginning of
      the text (left end), showing Prose Reading Neglect (PRN). The participants
      showing PRN differed from those not showing PRN only for the overall severity of
      neglect, and had a lesion centred on the insula, putamen and superior temporal
      gyrus. Double dissociations emerged between PRN and single word reading neglect,
      suggesting different cognitive requirements between the two tests: parallel
      processing in single word reading vs. serial analysis in text reading. Notably,
      the pattern of neglected text varied dramatically across participants presenting
      with PRN, including dissociations between reading performance of one and two
      columns text. Prose reading proved a complex and unique task which should be
      directly investigated to predict the effects of unilateral neglect. The outcome
      of this study should also inform clinical assessment and advises given to
      patients and care-givers. 

PMID- 24321198
TI  - Assessment of cognitive function across pregnancy using CANTAB: a longitudinal
      study.
AB  - Significant changes in endogenous plasma hormone levels are required to sustain
      pregnancy which provides a unique opportunity to study their effect on cognitive
      function. Four carefully selected tests from the Cambridge Neuropsychological
      Automated Test Battery (CANTAB) were administered to assess the cognitive
      function of a group of 23 women during each trimester of pregnancy and at three
      months following birth. Test scores were compared with a control group of 24 non
      pregnant women. The Edinburgh Postnatal Depression Scale was administered to
      assess anxiety and risk of depression. The National Adult Reading Test (NART) was
      used as a measure of verbal intelligence. Plasma hormone levels were measured at
      each time-point. The pregnant group scored significantly lower than the control
      group on the Spatial Recognition Memory (SRM) test at the second trimester and
      postpartum assessments (p?0.004). A significant pregnant group-time interaction
      (p=0.005) for SRM performance was demonstrated. Compared to their first trimester
      assessment, the pregnant group scored on average 11.7% less on each subsequent
      SRM test. The pregnant group reported more symptoms of anxiety and depression
      compared to the control group (EPDS-4 point increase in mean score at each
      assessment, p=0.002). There were no plasma hormone levels and test score
      associations identified. These data suggest SRM performance is adversely affected
      by pregnancy. Other aspects of executive function seem to be unaffected. Although
      the pregnant group reported more symptoms of anxiety and depression compared to
      the control group, analysis indicates that this confounder is not responsible for
      the SRM differences. 

PMID- 24321199
TI  - Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory
      in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis.
AB  - Epilepsy is characterized by the occurrence of repetitive seizures and can
      greatly affect a patient's cognition, particularly in terms of learning and
      memory. Orexin-A is an excitatory neuropeptide produced by the lateral
      hypothalamus that has been shown to be involved in learning and memory. A
      reduction in the levels of orexin-A after seizures may underlie the learning and
      memory impairments induced by epilepsy. Thus, we used pentylenetetrazol (PTZ)
      kindled rats to investigate the effects of orexin-A on learning and memory and
      the involvement of neurogenesis in the dentate gyrus in OX1R-mediated ERK1/2
      activation. A Morris water maze test revealed reduced escape latencies, prolonged
      times in the target quadrant and an increased number of platform crossings in PTZ
      kindled rats exposed to orexin-A. These ameliorating effects of orexin-A on
      spatial learning and memory were attenuated by the intracerebroventricular
      injection of the OX1R antagonist SB334867 or the ERK1/2 inhibitor U0126. Further
      studies using bromodeoxyuridine (BrdU) revealed that orexin-A increased the
      number of BrdU-positive cells, doublecortin (DCX)/BrdU levels and the number of
      NeuN/BrdU double-positive nuclei in the dentate gyrus of PTZ-kindled rats.
      However, these effects were inhibited by treatment with SB334867 or U0126. Taken
      together, these data suggest that orexin-A attenuated the impairment of spatial
      learning and memory in PTZ-kindled rats and that this attenuation involved
      neurogenesis in the dentate gyrus via OX1R-mediated ERK1/2 activation. 

PMID- 24321200
TI  - Influence of BCL2 gene in major depression susceptibility and antidepressant
      treatment outcome.
AB  - BACKGROUND: Our recent work indicated that low-expression of the anti-apoptotic
      protein B-cell/lymphoma 2 (Bcl-2) mRNA was observed among untreated major
      depressive disorder (MDD) patients, and the subsequent altered level of Bcl-2 was
      found to be close to the antidepressant treatment outcome. The primary aim of
      this present study was to examine whether a particular gene, encoding Bcl-2
      (BCL2) confers risk to MDD, and likewise to investigate whether this gene acts as
      an indicator of antidepressant treatment outcome. METHODS: We enrolled 178
      treatment-resistant depression (TRD) and 612 non-treatment-resistant depression
      (NTRD) patients as well as 725 healthy controls. In total, three selected tagging
      SNPs (tagSNPs) of BCL2 (rs2279115, rs1801018 and rs1564483) were genotyped to
      test for possible association. Using TaqMan relative quantitative real-time
      polymerase chain reaction (PCR), we analyzed leukocytic expression of BCL2 mRNA
      in 47 healthy subjects. RESULTS: Of the three SNPs, we observed no significant
      differences in genotype and allele frequencies between the MDD and control groups
      as well as between the TRD and NTRD groups. However, we found a significant
      association between the rs2279115C allele and TRD in males (corrected P=0.048)
      but not in females. Further real-time quantitative PCR analysis in healthy
      subjects revealed that the rs2279115 polymorphism significantly influenced BCL2
      mRNA expression (P=0.03). LIMITATIONS: This is a preliminary investigation with
      relatively small sample size and cross-sectional design. CONCLUSIONS: These
      initial findings strengthen the hypothesis that BCL2 may play an important role
      in mediating the outcome of antidepressant treatment, a result that may further
      be confirmed by future genetic studies from large-scale populations that can
      overcome the limited sample size of this preliminary finding.

PMID- 24321201
TI  - An increase in red blood cell distribution width from baseline predicts mortality
      in patients with severe sepsis or septic shock.
AB  - INTRODUCTION: A potential independent association was recently demonstrated
      between high red blood cell distribution width (RDW) and the risk of all-cause
      mortality in critically ill patients, although the mechanism underlying this
      relationship remains unclear. Little is known about the impact changes in RDW may
      have on survival in critically ill patients. Therefore, we investigated the
      prognostic significance of changes in RDW during hospital stay in patients with
      severe sepsis or septic shock. METHODS: We prospectively enrolled 329 patients
      who were admitted to the emergency department (ED) and received a standardized
      resuscitation algorithm (early-goal directed therapy) for severe sepsis or septic
      shock. The relationship between the changes in RDW during the first 72 hours
      after ED admission and all-cause mortality (28-day and 90-day) were analyzed by
      categorizing the patients into four groups according to baseline RDW value and
      DeltaRDW72hr-adm (RDW at 72 hours - RDW at baseline). RESULTS: The 28-day and 90
      day mortality rates were 10% and 14.6%, respectively. Patients with increased RDW
      at baseline and DeltaRDW72hr-adm >0.2% exhibited the highest risks of 28-day and
      90-day mortality, whereas the patients with normal RDW level at baseline and
      DeltaRDW72hr-adm <=0.2% (the reference group) had the lowest mortality risks. For
      90-day mortality, a significantly higher mortality risk was observed in the
      patients whose RDW increased within 72 hours of ED admission (normal RDW at
      baseline and DeltaRDW72hr-adm >0.2%), compared to the reference group. These
      associations remained unaltered even after adjusting for age, sex, Sequential
      Organ Failure Assessment (SOFA) score, Charlson Comorbidity Index, renal
      replacement therapy, albumin, hemoglobin, lactate, C-reactive protein and
      infection sites in multivariable models. CONCLUSIONS: We found that an increase
      in RDW from baseline during the first 72 hours after hospitalization is
      significantly associated with adverse clinical outcomes. Therefore, a combination
      of baseline RDW value and an increase in RDW can be a promising independent
      prognostic marker in patients with severe sepsis or septic shock.

PMID- 24321202
TI  - Enterobacteriaceae bacteremia: risk factors for ESBLPE.
AB  - OBJECTIVES: The increasing prevalence of extended spectrum beta-lactamase
      producing enterobacteriaceae (ESBLPE) requires defining the use of carbapenems in
      first intention. We analyzed the associations between enterobacteriaceae
      bacteremia (EbBact) and ESBLPE carriage during 10 years in a 950-bed teaching
      hospital. METHODS: We analyzed a 10-year (July 2001 to June 2011) prospective
      collection of bacteremia cases including 2 databases: (1) EbBact and (2) a
      computerized database of patients carrying EBLSE. Only one episode of EbBact was
      analyzed per patient and hospital stay. Factors associated with ESBLPE bacteremia
      were assessed by univariate and multivariate logistic regression analysis.
      RESULTS: Overall, 2355 cases of EbBact were identified, among which 135 (5.7%)
      were ESBLPE (2001-05: 1.4%, 2006-09: 7.6%, 2010-11: 14.2%). ESBLPE bacteremia was
      observed in 52 of the 88 (59%) patients carrying ESBLPE and in 83/2267 (3.7%)
      patients not known to be colonized with ESBLPE. Factors associated with ESBLPE
      bacteremia in patients not known to be colonized were: female gender (ORa=0.56,
      CI95% [0.34-0.91]), hospitalization in the ICU (ORa=2.51 [1.27-5.05]) or
      medical/surgical wards (ORa=1.83 [1.04-3.38]), the period (2006-09, ORa=4.08
      [2.21-8.16]; 2010-11, ORa=8.17 [4.14-17.06] compared to 2001-05), and history of
      EbBact (ORa=2.29 [0.97-4.79]). CONCLUSION: In case of EbBact, patients known to
      be colonized with ESBLPE present with ESBLPE bacteremia in more than half of the
      cases, requiring carbapenems as empirical antibiotic treatment. The global
      prevalence of ESBLPE among patients presenting with EbBact not known to be
      colonized with ESBLPE was 3.7%.

PMID- 24321203
TI  - How many suffice? A computational framework for sizing sentinel surveillance
      networks.
AB  - BACKGROUND: Data from surveillance networks help epidemiologists and public
      health officials detect emerging diseases, conduct outbreak investigations,
      manage epidemics, and better understand the mechanics of a particular disease.
      Surveillance networks are used to determine outbreak intensity (i.e., disease
      burden) and outbreak timing (i.e., the start, peak, and end of the epidemic), as
      well as outbreak location. Networks can be tuned to preferentially perform these
      tasks. Given that resources are limited, careful site selection can save costs
      while minimizing performance loss. METHODS: We study three different site
      placement algorithms: two algorithms based on the maximal coverage model and one
      based on the K-median model. The maximal coverage model chooses sites that
      maximize the total number of people within a specified distance of a site. The K
      median model minimizes the sum of the distances from each individual to the
      individual's nearest site. Using a ground truth dataset consisting of two million
      de-identified Medicaid billing records representing eight complete influenza
      seasons and an evaluation function based on the Huff spatial interaction model,
      we empirically compare networks against the existing Iowa Department of Public
      Health influenza-like illness network by simulating the spread of influenza
      across the state of Iowa. RESULTS: We show that it is possible to design a
      network that achieves outbreak intensity performance identical to the status quo
      network using two fewer sites. We also show that if outbreak timing detection is
      of primary interest, it is actually possible to create a network that matches the
      existing network's performance using 59% fewer sites. CONCLUSIONS: By simulating
      the spread of influenza across the state of Iowa, we show that our methods are
      capable of designing networks that perform better than the status quo in terms of
      both outbreak intensity and timing. Additionally, our results suggest that
      network size may only play a minimal role in outbreak timing detection. Finally,
      we show that it may be possible to reduce the size of a surveillance system
      without affecting the quality of surveillance information produced.

PMID- 24321204
TI  - Validity of the new A1 and A2 criteria for DSM-5 intermittent explosive disorder.
AB  - A disorder of impulsive aggression has been in the Diagnostic and Statistical
      Manual for Mental Disorders (DSM) since the first edition. In DSM-III, this
      disorder was codified as Intermittent Explosive Disorder (IED) and was thought to
      be rare. However, DSM criteria for IED were poorly operationalized and empiric
      research in IED was limited until the past decade when research criteria were
      developed. Subsequently, renewed interest in disorders of impulsive aggression
      led to a recent series of community based studies that have now documented IED to
      be as common as many other psychiatric disorders. Recent research indicates that
      the core of IED (A criteria) can be captured with new criteria that identify high
      frequency/low intensity aggressive outbursts (A1) and low frequency/hi intensity
      outbursts (A2). This paper presents new data regarding the phenomenology,
      comorbidity/life course of IED as a function of A1 and A2 criteria. Together with
      reanalysis of previously published data regarding family history, biomarkers, and
      treatment response in individuals with recurrent, problematic, impulsive
      aggression, these data provide empirical support for both A1 and A2 criteria for
      DSM-5 IED. 

PMID- 24321205
TI  - Predictors of remission from chronic depression: a prospective study in a
      nationally representative sample.
AB  - PURPOSE: The aims of this study were to identify predictors of remission from
      chronic depression in a prospective longitudinal general population survey;
      second, to determine the relative level functioning and well-being of those in
      remission. METHODS: The sample included respondents who met the criteria for
      major depressive disorder from Wave 1 (2001-2002) and through Wave 2 (2004-2005)
      of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
      RESULTS: Panic Disorder, Generalized Anxiety Disorder, Cluster B personality
      disorders and a history of Physical Abuse were correlated with reduced likelihood
      of chronic depression remission. The functioning and well-being of the remitted
      group was below the norm. CONCLUSIONS: These prognostic factors are similar to
      those found in clinical samples. Despite remission from chronic depression, a
      significant proportion have impairments in functioning.

PMID- 24321206
TI  - Characteristics of invasive Staphylococcus aureus infections in three regions of
      Korea, 2009-2011: a multi-center cohort study.
AB  - BACKGROUND: Despite the importance of invasive Staphylococcus aureus (ISA)
      infection, its overall burden in non-selected populations has only been defined
      in a small number of studies in Europe and North America. To define the
      characteristics of ISA infections in Korea, we conducted a multi-center cohort
      study to estimate population-based incidence rates. METHODS: We conducted a
      multicenter prospective cohort study at nine university-affiliated active
      surveillance core centers (ASCs) in three regions of Korea. To cover all
      available clinical microbiologic laboratories, we classified the laboratories in
      these regions into three groups according to their clinical environment as: 1)
      Nine ASCs, 2) Five major commercial laboratories and 3) Forty-four acute-care
      hospital-affiliated microbiology laboratories. We requested all the laboratories
      to report prospectively their numbers of cases of S. aureus isolated from
      normally sterile sites. Detailed clinical information was collected about the
      cases in the nine ASCs. RESULTS: From 1 July 2009 to 30 June 2011, a total of
      1,198 cases of ISA infection were identified at the nine ASCs, including 748
      (62%) methicillin-resistant S. aureus (MRSA) infections. Most (81%) ISA
      infections were healthcare-associated (HCA): 653 (55%) hospital-onset and 322
      (27%) community-onset. 223 (19%) were community-associated infections. The most
      common primary diagnosis was catheter-associated infection (225 cases, 19%).
      Respiratory tract infection (160, 13%), skin & soft tissue (152, 13%) and bone &
      joint infections (120, 10%) were also common. 30-day and 12-week mortality rates
      were 25.6% (262/1,024) and 36.5% (314/860), respectively. Complications,
      including metastatic infection within 12 weeks, occurred in 17.8% of ISA
      infections. The most common site of metastatic infection was the lung (9.8%,
      84/860). Based on the total of 2,806 observed cases of ISA infection, estimated
      annual rates of ISA and invasive MRSA infections were 43.3 and 27.7 per 100,000
      populations, respectively. CONCLUSIONS: Our data provide important information
      about the clinical characteristics of ISA infections. We estimate that over
      21,000 ISA infections and 13,000 invasive MRSA infections occurred in Korea in
      2010.

PMID- 24321208
TI  - Ursodeoxycholic acid and diets higher in fat prevent gallbladder stones during
      weight loss: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND & AIMS: The prevalence of gallstones is increasing in association with
      the obesity epidemic, but rapid weight loss also increases the risk of stone
      formation. We conducted a systematic review of the efficacy of strategies to
      prevent gallbladder stones in adults as they lose weight. METHODS: Randomized
      controlled trials of nonsurgical strategies to prevent gallstones were identified
      by electronic and manual searches. Our final analysis included 13 trials,
      comprising 1836 participants undergoing weight loss through dieting (8 trials) or
      bariatric surgery (5 trials). The trials compared ursodeoxycholic acid (UDCA) or
      high-fat weight loss diets with control interventions. We performed random
      effects meta-analyses and evaluated heterogeneity and bias with subgroup,
      sensitivity, regression, and sequential analysis. RESULTS: UDCA reduced the risk
      of ultrasound-verified gallstones compared with control interventions (risk
      ratio, 0.33; 95% confidence interval [CI], 0.18-0.60; number needed to treat, 9).
      This effect was significantly larger in trials of diets alone (risk ratio, 0.17;
      95% CI, 0.11-0.25) than in trials of patients who underwent bariatric surgery
      (risk ratio, 0.42; 95% CI, 0.21-0.83) (test for subgroup differences, P =.03).
      UDCA reduced the risk of cholecystectomy for symptomatic stones (risk ratio,
      0.20; 95% CI, 0.07-0.53). Diets high in fat content also reduced gallstones,
      compared with those with low fat content (risk ratio, 0.09; 95% CI, 0.01-0.61).
      The meta-analyses were confirmed in trials with a low risk of bias but not in
      sequential analysis. No additional beneficial or harmful outcomes were
      identified. CONCLUSIONS: On the basis of a meta-analysis of randomized controlled
      trials, during weight loss, UDCA and/or higher dietary fat content appear to
      prevent formation of gallstones.

PMID- 24321207
TI  - Post-treatment levels of alpha-fetoprotein predict incidence of hepatocellular
      carcinoma after interferon therapy.
AB  - BACKGROUND & AIMS: In patients with chronic hepatitis C virus (HCV) infection,
      lack of sustained virologic response (SVR) 24 weeks after the end of interferon
      therapy is a significant risk factor for hepatocellular carcinoma (HCC). Although
      many pretreatment factors are known to affect HCC incidence, less is known about
      post-treatment factors-many change during the course of interferon therapy.
      METHODS: We performed a prospective study, collecting data from 2659 patients
      with chronic hepatitis C without a history of HCC who had been treated with
      pegylated interferon (Peg-IFN) plus ribavirin from 2002 through 2008 at hospitals
      in Japan. Biopsy specimens were collected before treatment; all patients received
      Peg-IFN plus ribavirin for 48 to 72 weeks (HCV genotype 1) or 24 weeks (HCV
      genotype 2). Hematologic, biochemical, and virologic data were collected every 4
      weeks during treatment and every 6 months after treatment. HCC was diagnosed
      based on angiography, computed tomography, and/or magnetic resonance imaging
      findings. RESULTS: HCC developed in 104 patients during a mean observation period
      of 40 months. Older age, male sex, lower platelet counts and higher levels of
      alpha-fetoprotein at baseline, and lack of an SVR were significant risk factors
      for HCC. The cumulative incidence of HCC was significantly lower in patients
      without SVRs who relapsed than those with no response to treatment. Levels of
      alpha-fetoprotein 24 weeks after the end of treatment (AFP24) were significantly
      lower than levels of alpha-fetoprotein at baseline in patients with SVRs and
      those who relapsed, but not in nonresponders. Post-treatment risk factors for HCC
      among patients with SVRs included higher AFP24 level and older age; among those
      without SVRs, risk factors included higher AFP24 level, integrated level of
      alanine aminotransferase, older age, and male sex. AFP24 (>=10 ng/mL, 10-5 ng/mL,
      and then <5 ng/mL) was a better predictor of HCC incidence than pretreatment
      level of AFP among patients with and without SVRs. CONCLUSIONS: In patients with
      chronic HCV infection, levels of alpha-fetoprotein decrease during interferon
      therapy. High post-treatment levels of alpha-fetoprotein predict HCC, regardless
      of whether patients achieve an SVR. University Hospital Medical Information
      Network Clinical Trials Registry: C000000196, C000000197.

PMID- 24321209
TI  - Good maternal and fetal outcomes for pregnant women with primary biliary
      cirrhosis.
AB  - BACKGROUND & AIMS: Up to 25% of patients diagnosed with primary biliary cirrhosis
      (PBC) are of childbearing age. However, little is known about disease course
      during pregnancy. METHODS: We performed a retrospective analysis of women with
      PBC during pregnancy using a representative large cohort of patients attending
      the Liver Center at Toronto Western hospital from January 1979 through June 2009
      (n = 306). Statistical analysis was performed by using R statistical software.
      RESULTS: We identified 32 women (50 pregnancies) who either became pregnant after
      a diagnosis of PBC or in whom pregnancy led to diagnosis. Liver biochemistry
      remained stable in most patients (70%) throughout pregnancy. However, 23 of 32
      patients (72%) had a flare in biochemical disease activity post partum, which was
      unrelated to biochemical disease activity before conception (P = .53), or during
      the gestational period (P = .14). No adverse maternal events were observed during
      pregnancy or post partum, and only 2 of 32 of women (6%) developed progressive
      disease after delivery. De novo pruritus developed during pregnancy in 17 of 32
      women (53%), whereas itch that existed before conception worsened for 4 patients.
      Fifteen of 21 women (71%) with pregnancy-related pruritus required symptom
      specific therapy. Twenty-nine of 32 women (91%) had at least 1 successful live
      birth; adverse fetal outcome was not influenced by biochemical disease activity
      before conception (P = .24) or during pregnancy (P = 1.00). CONCLUSION: Pregnancy
      in women with PBC is frequently symptomatic but mostly uneventful. The majority
      of women maintain stable liver biochemistry during pregnancy, although postpartum
      biochemical exacerbations are common.

PMID- 24321210
TI  - Vascular endothelia growth factor targeted therapy may improve the effect of
      dendritic cell-based cancer immune therapy.

PMID- 24321211
TI  - Drug resistance mediated changes in lymphendothelial tumor cell intravasation.

PMID- 24321212
TI  - Intestinal inflammation in a murine model of autism spectrum disorders.
AB  - Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders
      characterized by impairments in communication, social interest and stereotypical
      behaviour. Dysfunction of the intestinal tract is reported in patients with ASD
      and implicated in the development and severity of ASD symptoms. However, more
      research is required to investigate the association of intestinal problems with
      ASD and the potential underlying mechanisms. The purpose of this study was to
      investigate comorbid symptoms of intestinal inflammation in a murine model of ASD
      induced by prenatal exposure to valproic acid (VPA). Pregnant BALB/c females were
      treated subcutaneously with 600 mg/kg VPA or phosphate buffered saline on
      gestational day 11. Offspring were housed with their mother until weaning on
      postnatal day 21 (P21). All pups were exposed to a social behaviour test on P28.
      Inflammatory correlates and activity of the serotonergic system were measured in
      brain and intestinal tissue. Here we demonstrate, in addition to reduced social
      behaviour and increased expression of neuroinflammatory markers in the brain,
      that VPA in utero- exposed male offspring showed epithelial cell loss and
      neutrophil infiltration in the intestinal tract. Furthermore, reduced levels of
      serotonin were not only observed the prefrontal cortex and amygdala of VPA in
      utero- exposed males, but also in the small intestine. Overall, we demonstrate
      that gender-specific inflammatory conditions are present in the small intestines
      of VPA in utero- exposed mice and are accompanied by a disturbed serotonergic
      system in the brain as well as in the intestinal tract.

PMID- 24321214
TI  - Sarm1, a neuronal inflammatory regulator, controls social interaction,
      associative memory and cognitive flexibility in mice.
AB  - Impaired neurodevelopment leads to several psychiatric disorders, including
      autism, schizophrenia and attention deficiency hyperactivity disorder. Our prior
      study showed that sterile alpha and TIR motif-containing 1 protein (Sarm1)
      regulates neuronal morphogenesis through at least two pathways. Sarm1 controls
      neuronal morphogenesis, including dendritic arborization, axonal outgrowth and
      establishment of neuronal polarity, through the MKK-JNK pathway. Neuronally
      expressed Sarm1 also regulates the expression of inflammatory cytokines in the
      brain, which have also been shown to impact brain development and function.
      Because the reduction of Sarm1 expression negatively influences neuronal
      development, here we investigated whether Sarm1 controls mouse behaviors. We
      analyzed two independent Sarm1 transgenic mouse lines using a series of
      behavioral assays, and found that the reduction of Sarm1 protein levels had a
      limited effect on locomotion and anxiety. However, Sarm1 knockdown mice exhibited
      impairments in cued and contextual fear conditioning as well as cognitive
      flexibility. Moreover, the three-chambered social test, reciprocal social
      interaction and social transmission of food preference further illustrated
      deficiencies in Sarm1 knockdown mice in social interaction. These findings
      suggest that Sarm1, a molecule that regulates innate immunity and neuronal
      morphogenesis, regulates social behaviors and cognition. We conclude that Sarm1
      is involved in immune response, neural development and psychiatric disorders. 

PMID- 24321215
TI  - Toxoplasma gondii impairs memory in infected seniors.
AB  - Almost 30% of humans present a Toxoplasma gondii positive antibody status and its
      prevalence increases with age. The central nervous system is the main target.
      However, little is known about the influence of asymptomatic i.e. latent
      Toxoplasmosis on cognitive functions in humans. To investigate neurocognitive
      dysfunctions in asymptomatic older adults with T. gondii positive antibody status
      a double-blinded neuropsychological study was conducted. The participants were
      classified from a population-based sample (N=131) of healthy participants with an
      age of 65 years and older into two groups with 42 individuals each: Toxoplasmosis
      positive (T-pos; IgG>50 IU/ml) and Toxoplasmosis negative (T-neg; IgG=0 IU/ml).
      The outcome measures were a computer-based working-memory test (2-back) and
      several standardized psychometric tests of memory and executive cognitive
      functions. T-pos seniors showed an impairment of different aspects of memory. The
      rate of correctly detected target symbols in a 2-back task was decreased by
      nearly 9% (P=0.020), corresponding to a performance reduction of about 35% in
      working memory relative to the T-neg group. Moreover, T-pos seniors had a lower
      performance in a verbal memory test, both regarding immediate recall (10%
      reduction; P=0.022), delayed recognition (6%; P=0.037) and recall from long-term
      memory assessed by the word fluency tests (12%; P=0.029). In contrast, executive
      functions were not affected. The effects remained mostly unchanged after
      controlling for medication. The impairment of memory functions in T-pos seniors
      was accompanied by a decreased self-reported quality of life. Because of the high
      prevalence of asymptomatic Toxoplasmosis and an increasing population of older
      adults this finding is of high relevance for public health.

PMID- 24321213
TI  - Adrenomedullin protects from experimental autoimmune encephalomyelitis at
      multiple levels.
AB  - Adrenomedullin is a neuropeptide known for its cardiovascular activities and anti
      inflammatory effects. Here, we investigated the effect of adrenomedullin in a
      model of experimental autoimmune encephalomyelitis (EAE) that mirrors chronic
      progressive multiple sclerosis. A short-term systemic treatment with
      adrenomedullin reduced clinical severity and incidence of EAE, the appearance of
      inflammatory infiltrates in spinal cord and the subsequent demyelination and
      axonal damage. This effect was exerted at multiple levels affecting both early
      and late events of the disease. Adrenomedullin decreased the presence/activation
      of encephalitogenic Th1 and Th17 cells and down-regulated several inflammatory
      mediators in peripheral lymphoid organs and central nervous system. Noteworthy,
      adrenomedullin inhibited the production by encephalitogenic cells of osteopontin
      and of Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), two critical
      cytokines in the development of EAE. At the same time, adrenomedullin increased
      the number of IL-10-producing regulatory T cells with suppressive effects on the
      progression of EAE. Furthermore, adrenomedullin generated dendritic cells with a
      semi-mature phenotype that impaired encephalitogenic responses in vitro and in
      vivo. Finally, adrenomedullin regulated glial activity and favored an active
      program of neuroprotection/regeneration. Therefore, the use of adrenomedullin
      emerges as a novel multimodal therapeutic approach to treat chronic progressive
      multiple sclerosis. 

PMID- 24321216
TI  - Adrenergic and glucocorticoid modulation of the sterile inflammatory response.
AB  - Exposure to an intense, acute stressor, in the absence of a pathogen, alters
      immune function. Exposure to a single bout of inescapable tail shock increases
      plasma and tissue concentrations of cytokines, chemokines, and the danger
      associated molecular pattern (DAMP) Hsp72. Although previous studies have
      demonstrated that adrenergic receptor (ADR) and glucocorticoid receptor (GCR)
      mediated pathways alter pathogen or microbial associated molecular pattern (MAMP)
      evoked levels of cytokines, chemokines, and Hsp72, far fewer studies have tested
      the role of these receptors across multiple inflammatory proteins or tissues to
      elucidate the differences in magnitude of stress-evoked sterile inflammatory
      responses. The goals of the current study were to (1) compare the sterile
      inflammatory response in the circulation, liver, spleen, and subcutaneous (SQ)
      adipose tissue by measuring cytokine, chemokine, and DAMP (Hsp72) responses; and
      (2) to test the role of alpha-1 (alpha1), beta-1 (beta1), beta-2 (beta2), and
      beta-3 (beta3) ADRs, as well as GCRs in signaling the sterile inflammatory
      response. The data presented indicate plasma and SQ adipose are significantly
      more stress responsive than the liver and spleen. Further, administration of ADR
      and GCR-specific antagonists revealed both similarities and differences in the
      signaling mechanisms of the sterile inflammatory response in the tissues studied.
      Finally, given the selective increase in the chemokine monocyte chemotactic
      protein-1 (MCP-1) in SQ tissue, it may be that SQ adipose is an important site of
      leukocyte migration, possibly in preparation for infection as a consequence of
      wounding. The current study helps further our understanding of the tissue
      specific differences of the stress-induced sterile inflammatory response. 

PMID- 24321218
TI  - A clinical study of non-parkinsonian tremor in Moroccan patients.
AB  - OBJECTIVE: To report the characteristics of the most frequent tremors in a
      population of Moroccan patients. BACKGROUND: Tremor is the most common movement
      disorder. It implies a wide variety of disorders with Parkinson's disease and
      essential tremor being the most frequent. METHODS: A retrospective study of 148
      patients with tremor referred to our movement disorders outpatient clinic was
      performed. Clinical features and treatment regimens were analyzed. Patients with
      parkinsonian tremor were excluded. RESULTS: We included 62 patients with non
      parkinsonian tremor. The etiologies were as follows: essential tremor (54.8%),
      dystonic tremor (19.4%), tremor associated with dystonia (14.5%), enhanced
      physiological tremor (3.2%), cerebellar tremor (3.2%), psychogenic tremor (3.2%)
      and Holmes' tremor (1.6%). The characteristics of essential tremor patients were
      analyzed. Female patients accounted for 67.6% of patients. Mean age at the onset
      of tremor was 52.2 +/- 16.4 years. Family history of tremor was reported in 17.6%
      of cases. Tremor affected the arms (94.1%), head (52.9%), voice (35.3%) and legs
      (8.8%). Tremor was bilateral in 87.5% but was asymmetrical in 50% of patients.
      Patients had postural tremor (76.5%), kinetic tremor (79.4%) and rest tremor
      (associated in 11.8%). Treatment relied on propranolol (88.3%), primidone
      (14.7%), gabapentin (14.7%), clonazepam (14.7%), alprazolam (11.8%), topiramate
      (5.9%) and, in one patient, radiosurgery. CONCLUSIONS: Essential tremor was the
      predominant diagnosis, confirming its high prevalence. There was a predominance
      of female patients and a peak of age at onset in the fifth and sixth decades.
      Asymmetry of the disease was noted in half of patients.

PMID- 24321219
TI  - Optimizing emergency department imaging utilization through advanced health
      record technology.

PMID- 24321217
TI  - "Causes of death in asthma, COPD and non-respiratory hospitalized patients: a
      multicentric study".
AB  - BACKGROUND: There is limited information on the causes of death in asthma
      patients.To determine the causes of death in hospitalized asthmatic patients and
      to compare with those observed in COPD patients and non-respiratory individuals,
      with a particular interest in associations with previous cardiovascular disease.
      METHODS: Retrospective case-control study which analyzed the deaths of all
      hospitalized patients admitted for any reason during January, April, July and
      October of 2008 in 13 Spanish centers. Medical records of deceased patients were
      reviewed, and demographic and clinical data were collected. RESULTS: A total of
      2,826 deaths (mean age 75 years, 56% men) were included in the analysis, of which
      82 (2.9%) were of patients with asthma and 283 (10%) with COPD.The most common
      causes of death in asthma patients were cardiovascular diseases (29.3%),
      malignancies (20.7%) and infections (14.6%); in COPD patients they were
      malignancies (26.5%), acute respiratory failure (25.8%) and cardiovascular
      diseases (21.6%). Asthma, compared to COPD patients, died significantly less
      frequently from acute respiratory failure and lung cancer. A multivariate
      logistic regression analysis failed to associate asthma with cardiovascular
      deaths. CONCLUSIONS: Cardiovascular disease is the most frequent cause of death
      among hospitalized asthma patients. The specific causes of death differ between
      asthma and COPD patients.

PMID- 24321220
TI  - The diversion of outpatient echocardiography from private offices to higher cost
      hospital facilities: an unanticipated effect of code bundling.
AB  - PURPOSE: In 2009, the add-on codes for spectral Doppler and color flow Doppler
      echocardiography were bundled into the code for primary transthoracic
      echocardiography. The relative value units for the new single code were
      substantially lower than the previous sum for the 3 codes. The purpose of this
      study was to see how this affected the distribution of outpatient
      echocardiographic studies between cardiology offices and hospital outpatient
      departments (HOPDs). METHODS: The 2005 to 2011 Medicare databases were used. All
      echocardiography Current Procedural Terminology codes were selected. Specialty
      codes identified those done by cardiologists (who do most echocardiographic
      studies). Place-of-service codes identified those done in offices and HOPDs.
      Procedure volumes and utilization rates per 1,000 were determined each year
      before and after bundling occurred in 2009. RESULTS: Cardiologists' office
      echocardiography utilization rate rose from 219.5 per 1,000 in 2005 to 257.1 in
      2008 (+17%), then dropped to 100.0 in 2009 (-61%) because of bundling. Their HOPD
      echocardiography rate rose from 72.2 in 2005 to 76.5 in 2008 (+6%), then dropped
      to 35.0 in 2009 (-54%). From 2009 to 2011, cardiologists' office echocardiography
      rate dropped again from 100.0 to 88.8 (-11%), while their HOPD rate increased
      from 35.0 to 46.1 (+32%). CONCLUSIONS: Echocardiography code bundling produced
      the expected sharp drop in outpatient claims from cardiologists in 2009. But
      after bundling, office echocardiography rates continued to drop, while HOPD rates
      increased. It seems that in this instance, code bundling led to the closure of
      many cardiology offices and a resultant shift of echocardiography from that lower
      cost setting to the higher cost HOPD setting.

PMID- 24321221
TI  - Current opinions on medical radiation: a survey of oncologists regarding
      radiation exposure and dose reduction in oncology patients.
AB  - PURPOSE: The aim of this study was to evaluate oncologists' opinions about the
      use of ionizing radiation in medical imaging of oncology patients. METHODS: An
      electronic survey was e-mailed to 2,725 oncologists at the top 50 National Cancer
      Institute-funded cancer centers. The survey focused on opinions on CT dose
      reduction in oncology patients and current philosophies behind long-term imaging
      in these patients. RESULTS: The response rate was 15% (415 of 2,725). Eighty-two
      percent of respondents stated that their patients or families have expressed
      anxiety regarding radiation dose from medical imaging. Although fewer than half
      of oncologists (48%) did not know whether CT dose reduction techniques were used
      at their institutions, only 25% were concerned that small lesions may be missed
      with low-dose CT techniques. The majority of oncologists (63%) follow National
      Comprehensive Cancer Network guidelines for imaging follow-up, while the
      remainder follow other national guidelines such as those of the Children's
      Oncology Group, the American Society of Clinical Oncology, or clinical trials.
      Ninety percent of respondents believe that long-term surveillance in oncology
      patients is warranted, particularly in patients with breast cancer, melanoma,
      sarcoma, and pediatric malignancies. The majority of oncologists would consider
      the use of low-dose CT imaging in specific patient populations: (1) children and
      young women, (2) those with malignancies that do not routinely metastasize to the
      liver, and (3) patients undergoing surveillance imaging. CONCLUSIONS: Cumulative
      radiation exposure is a concern for patients and oncologists. Among oncologists,
      there is support for long-term imaging surveillance despite lack of national
      guidelines.

PMID- 24321222
TI  - Dosimetric difference amongst 3 techniques: TomoTherapy, sliding-window intensity
      modulated radiotherapy (IMRT), and RapidArc radiotherapy in the treatment of late
      stage nasopharyngeal carcinoma (NPC).
AB  - To investigate the dosimetric difference amongst TomoTherapy, sliding-window
      intensity-modulated radiotherapy (IMRT), and RapidArc radiotherapy in the
      treatment of late-stage nasopharyngeal carcinoma (NPC). Ten patients with late
      stage (Stage III or IV) NPC treated with TomoTherapy or IMRT were selected for
      the study. Treatment plans with these 3 techniques were devised according to
      departmental protocol. Dosimetric parameters for organ at risk and treatment
      targets were compared between TomoTherapy and IMRT, TomoTherapy and RapidArc, and
      IMRT and RapidArc. Comparison amongst the techniques was done by statistical
      tests on the dosimetric parameters, total monitor unit (MU), and expected
      delivery time. All 3 techniques achieved similar target dose coverage.
      TomoTherapy achieved significantly lower doses in lens and mandible amongst the
      techniques. It also achieved significantly better dose conformity to the
      treatment targets. RapidArc achieved significantly lower dose to the eye and
      normal tissue, lower total MU, and less delivery time. The dosimetric advantages
      of the 3 techniques were identified in the treatment of late-stage NPC. This may
      serve as a guideline for selection of the proper technique for different clinical
      cases. 

PMID- 24321224
TI  - Ticks in the wrong boxes: assessing error in blanket-drag studies due to
      occasional sampling.
AB  - BACKGROUND: The risk posed by ticks as vectors of disease is typically assessed
      by blanket-drag sampling of host-seeking individuals. Comparisons of peak
      abundance between plots - either in order to establish their relative risk or to
      identify environmental correlates - are often carried out by sampling on one or
      two occasions during the period of assumed peak tick activity. METHODS: This
      paper simulates this practice by 're-sampling' from model datasets derived from
      an empirical field study. Re-sample dates for each plot are guided by either the
      previous year's peak at the plot, or the previous year's peak at a similar,
      nearby plot. Results from single, double and three-weekly sampling regimes are
      compared. RESULTS: Sampling on single dates within a two-month window of assumed
      peak activity has the potential to introduce profound errors; sampling on two
      dates (double sampling) offers greater precision, but three-weekly sampling is
      the least biased. CONCLUSIONS: The common practice of sampling for the abundance
      of host-seeking ticks on single dates in each plot-year should be strenuously
      avoided; it is recommended that field acarologists employ regular sampling
      throughout the year at intervals no greater than three weeks, for a variety of
      epidemiological studies.

PMID- 24321223
TI  - Do cleft lip and palate patients opt for secondary corrective surgery of upper
      lip and nose, frequently?
AB  - PURPOSE: This prospective study was aimed at assessing cleft lip and palate (CLP)
      patients' opinions and attitudes towards their upper lip and nose and the number
      of secondary corrective surgical interventions electively undertaken to upper lip
      and nose that were carried out during a 2 year follow-up period. MATERIALS AND
      METHODS: During a 2 year follow-up period CLP outpatients were recruited for the
      study who attended follow-up examinations at a cleft lip and palate craniofacial
      center and received a recommendation for secondary corrective facial surgery. The
      participants filled in a questionnaire that included questions regarding the
      patients' opinions and attitudes towards appearance of lip and nose and need for
      secondary corrective facial surgery. During an additional interval of 2 years the
      rate of patients who underwent secondary corrective surgery to lip and nose was
      documented. RESULTS: Out of 362 CLP patients 37 (mean age 13.6 +/- 7.6 years)
      received a recommendation for secondary corrective surgery to upper lip and/or
      nose. 22 patients (mean age 12.6 +/- 6.3 years) filled in the questionnaire
      (response rate of 62.1%). The satisfaction with the overall facial appearance
      following the first corrective operation was statistically significantly better
      than the satisfaction with the nose (p = .016). The satisfaction with facial
      symmetry (5.6 +/- 2.0) did not differ statistically significantly from the
      overall satisfaction with the facial appearance (6.2 +/- 1.8; p = .093).
      Significantly fewer patients (n = 9) opted for corrective surgery compared to the
      number of patients who got the recommendation to have secondary corrective
      surgery done (n = 22, p < .0005). CONCLUSIONS: The findings of the present study
      may reflect a high overall patient satisfaction with the primary treatment
      outcome following surgery for CLP. Perceived patient need for secondary operation
      for the lip/nose may be as low as 5%.

PMID- 24321225
TI  - Source-based morphometry of gray matter volume in patients with schizophrenia who
      have persistent auditory verbal hallucinations.
AB  - Abnormal structure of frontal and temporal brain regions has been suggested to
      occur in patients with schizophrenia who have frequent auditory verbal
      hallucinations (AVH). However, it is unknown whether this is specific to this
      patient subgroup. This study tested the hypothesis that frontotemporal gray
      matter volume changes would characterize patients with persistent AVH (pAVH) in
      contrast to healthy controls and patients without AVH. Using structural magnetic
      resonance imaging at 3T, we studied 20 patients with schizophrenia and 14 matched
      healthy controls. Ten patients were classified as having chronic and treatment
      resistant AVH, whereas the remaining 10 patients either never had AVH in the past
      or were in full remission with regard to AVH (nAVH). Using a multivariate
      statistical technique for structural data, i.e. "source-based morphometry" (SBM),
      we investigated naturally grouping patterns of gray matter volume variation among
      individuals, the magnitude of their expression between-groups and the
      relationship between gray matter volume and AVH-specific measures. SBM identified
      a reduction of medial and inferior frontal, insular and bilateral temporal gray
      matter volume between pAVH and nAVH. This pattern did not differ between nAVH
      patients and controls and was associated with "physical" AVH characteristics
      (such as symptom duration, location, frequency and intensity) in the pAVH patient
      group. These results suggest that a pattern of lower gray matter volume in medial
      frontal, insular and bilateral temporal cortical regions differentiates between
      patients with persistent AVH and non-hallucinating patients. Moreover, the data
      support a specific role of this neural pattern in AVH symptom expression. 

PMID- 24321226
TI  - Molecular and metabolic pattern classification for detection of brain glioma
      progression.
AB  - OBJECTIVES: The ability to differentiate between brain tumor progression and
      radiation therapy induced necrosis is critical for appropriate patient
      management. In order to improve the differential diagnosis, we combined fluorine
      18 2-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET), proton
      magnetic resonance spectroscopy ((1)H MRS) and histological data to develop a
      multi-parametric machine-learning model. METHODS: We enrolled twelve post-therapy
      patients with grade 2 and 3 gliomas that were suspicious of tumor progression.
      All patients underwent (18)F-FDG PET and (1)H MRS. Maximal standardized uptake
      value (SUVmax) of the tumors and reference regions were obtained. Multiple 2D
      maps of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) of the tumors
      were generated. A support vector machine (SVM) learning model was established to
      take imaging biomarkers and histological data as input vectors. A combination of
      clinical follow-up and multiple sequential MRI studies served as the basis for
      assessing the clinical outcome. All vector combinations were evaluated for
      diagnostic accuracy and cross validation. The optimal cutoff value of individual
      parameters was calculated using Receiver operating characteristic (ROC) plots.
      RESULTS: The SVM and ROC analyses both demonstrated that SUVmax of the lesion was
      the most significant single diagnostic parameter (75% accuracy) followed by Cho
      concentration (67% accuracy). SVM analysis of all paired parameters showed SUVmax
      and Cho concentration in combination could achieve 83% accuracy. SUVmax of the
      lesion paired with SUVmax of the white matter as well as the tumor Cho paired
      with the tumor Cr both showed 83% accuracy. These were the most significant
      paired diagnostic parameters of either modality. Combining all four parameters
      did not improve the results. However, addition of two more parameters, Cho and Cr
      of brain parenchyma contralateral to the tumor, increased the accuracy to 92%.
      CONCLUSION: This study suggests that SVM models may improve detection of glioma
      progression more accurately than single parametric imaging methods. RESEARCH
      SUPPORT: National Cancer Institute, Cancer Center Support Grant Supplement Award,
      Imaging Response Assessment Teams.

PMID- 24321227
TI  - Epidemic dynamics of a vector-borne disease on a villages-and-city star network
      with commuters.
AB  - We develop a star-network of connections between a central city and peripheral
      villages and analyze the epidemic dynamics of a vector-borne disease as
      influenced by daily commuters. We obtain an analytical solution for the global
      basic reproductive number R0 and investigate its dependence on key parameters for
      disease control. We find that in a star-network topology the central hub is not
      always the best place to focus disease intervention strategies. Disease control
      decisions are sensitive to the number of commuters from villages to the city as
      well as the relative densities of mosquitoes between villages and city. With more
      commuters it becomes important to focus on the surrounding villages. Commuting to
      the city paradoxically reduces the disease burden even when the bulk of
      infections are in the city because of the resulting diluting effects of
      transmissions with more commuters. This effect decreases with heterogeneity in
      host and vector population sizes in the villages due to the formation of
      peripheral epicenters of infection. We suggest that to ensure effective control
      of vector-borne diseases in star networks of villages and cities it is also
      important to focus on the commuters and where they come from. 

PMID- 24321228
TI  - Shame in patients with narcissistic personality disorder.
AB  - Shame has been described as a central emotion in narcissistic personality
      disorder (NPD). However, there is a dearth of empirical data on shame in NPD.
      Patients with NPD (N=28), non-clinical controls (N=34) and individuals with
      borderline personality disorder (BPD, N=31) completed self-report measures of
      state shame, shame-proneness, and guilt-proneness. Furthermore, the Implicit
      Association Test (IAT) was included as a measure of implicit shame, assessing
      implicit shame-self associations relative to anxiety-self associations.
      Participants with NPD reported higher levels of explicit shame than non-clinical
      controls, but lower levels than patients with BPD. Levels of guilt-proneness did
      not differ among the three study groups. The implicit shame-self associations
      (relative to anxiety-self associations) were significantly stronger among
      patients with NPD compared to nonclinical controls and BPD patients. Our findings
      indicate that shame is a prominent feature of NPD. Implications for diagnosis and
      treatment are discussed. 

PMID- 24321229
TI  - An investigation of gender differences in semantic processing in individuals with
      high schizotypy.
AB  - Semantic processing deficits may underlie thought disorder in schizophrenia.
      Cognitive Disorganisation (CD) in schizotypy is a thought disorder analogue. This
      study established CD was related to abnormal strategic semantic processing on an
      indirect semantic priming task. There were no gender differences. It also
      confirms the importance of replicating underpowered studies. 

PMID- 24321231
TI  - A biomechanical comparison of anterior cruciate ligament suspensory fixation
      devices in a porcine cadaver model.
AB  - BACKGROUND: Suspensory fixation use during anterior cruciate ligament
      reconstruction has increased due to ease of use and high pullout strength. We
      hypothesize that there are no significant differences in biomechanical
      performance among four types of suspensory fixation devices: Stryker VersiTomic G
      Lok, Smith & Nephew Endobutton, Biomet ToggleLoc, and Arthrex RetroButton.
      METHODS: Forty fresh frozen porcine femurs and flexor digitorum profundus tendons
      were obtained. Each tendon graft was sized to 8.5mm or 9.0mm. Ten of each device
      were used to fix the grafts in the femur at the 2 o'clock (left) or 10 o'clock
      (right) position. The graft-femur complex was secured to a servohydraulic test
      machine in line with the femoral tunnel. The graft was cyclically loaded from 50
      to 250 N for 1000 cycles at 1 Hz then loaded to failure at 20mm/min. Actuator
      load and displacement were recorded. Data were analyzed with multiple one-way
      ANOVA and Tukey HSD post-hoc tests. Bonferroni correction was applied resulting
      in P <= 0.005 considered statistically significant for ANOVA, P <= 0.05 for
      Tukey. FINDINGS: There were no significant differences in cyclic displacement
      among any of the groups (P=0.43). The only significant difference in failure
      properties is the Endobutton exhibited at least 50% greater displacement at
      failure than the other three devices. INTERPRETATION: Suspensory femoral soft
      tissue fixation devices are biomechanically similar with respect to failure load
      but differ in failure displacement. However, there was no significant difference
      in displacement after cyclic loading. All four fixation devices should withstand
      the forces associated with daily activities without failure.

PMID- 24321230
TI  - The role of intestinal mucosa injury induced by intra-abdominal hypertension in
      the development of abdominal compartment syndrome and multiple organ dysfunction
      syndrome.
AB  - INTRODUCTION: Abdominal distension is common in critical illness. There is a
      growing recognition that intra-abdominal hypertension (IAH) may complicate
      nonsurgical critical illness as well as after abdominal surgery. However, the
      pathophysiological basis of the injury to the intestinal mucosal barrier and its
      influence on the onset of abdominal compartment syndrome (ACS) and multiorgan
      dysfunction syndrome (MODS) remain unclear. We measured intestinal
      microcirculatory blood flow (MBF) during periods of raised intra-abdominal
      pressure (IAP) and examined how this influenced intestinal permeability, systemic
      endotoxin release, and histopathological changes. METHODS: To test different
      grades of IAH to the injury of intestinal mucosa, 96 New Zealand white rabbits
      aged 5 to 6 months were exposed to increased IAP under nitrogen pneumoperitoneum
      of 15 mmHg or 25 mmHg for 2, 4 or 6 hours. MBF was measured using a laser Doppler
      probe placed against the jejunal mucosa through a small laparotomy. Fluorescein
      isothiocyanate (FITC)-conjugated dextran was administered by gavage. Intestinal
      injury and permeability were measured using assays for serum FITC-dextran and
      endotoxin, respectively, after each increase in IAP. Structural injury to the
      intestinal mucosa at different levels of IAH was confirmed by light and
      transmission electron microscopy. RESULTS: MBF reduced from baseline by 40% when
      IAP was 15 mmHg for 2 hours. This doubled to 81% when IAP was 25 mmHg for 6
      hours. Each indicator of intestinal injury increased significantly,
      proportionately with IAP elevation and exposure time. Baseline serum FITC-dextran
      was 9.30 (+/- SD 6.00) MUg/ml, rising to 46.89 (+/-13.43) MUg/ml after 15 mmHg
      IAP for 4 hours (P <0.01), and 284.59 (+/- 45.18) MUg/ml after 25 mmHg IAP for 6
      hours (P <0.01). Endotoxin levels showed the same pattern. After prolonged
      exposure to increased IAP, microscopy showed erosion and necrosis of jejunal
      villi, mitochondria swelling and discontinuous intracellular tight junctions.
      CONCLUSIONS: Intra-abdominal hypertension can significantly reduce MBF in the
      intestinal mucosa, increase intestinal permeability, result in endotoxemia, and
      lead to irreversible damage to the mitochondria and necrosis of the gut mucosa.
      The dysfunction of the intestinal mucosal barrier may be one of the important
      initial factors responsible for the onset of ACS and MODS.

PMID- 24321232
TI  - Happy 50th anniversary Cortex!

PMID- 24321233
TI  - Nonsense-mediated mRNA decay due to a CACNA1C splicing mutation in a patient with
      Brugada syndrome.
AB  - BACKGROUND: Brugada syndrome (BrS) is an inherited cardiac arrhythmia associated
      with sudden death due to ventricular fibrillation. Mutations in genes related to
      the cardiac L-type calcium channel have been reported to be causative of BrS.
      Generally, the messenger RNA (mRNA) that contains a nonsense mutation is rapidly
      degraded via its decay pathway, which is known as nonsense-mediated mRNA decay
      (NMD). Previously, we reported a male patient with BrS who carried c.1896G>A (the
      first nucleotide of CACNA1C exon 14), which caused a synonymous mutation,
      p.R632R. OBJECTIVE: To examine how the synonymous CACNA1C mutation p.R632R
      produces the phenotype of BrS, with a special emphasis on the splicing error and
      NMD processes. METHODS: We extracted mRNA from leukocytes of the proband and his
      2 children and performed reverse transcription polymerase chain reaction.
      Complementary DNAs were checked by using direct sequencing and quantitative
      analysis. RESULTS: The subsequent sequence electropherogram of the complementary
      DNAs did not show the substitution of the nucleotide identified in the genomic
      DNA of the proband. In the mRNA quantification analysis, we confirmed that
      reduction in the CACNA1C expression level was suspected to be caused by NMD.
      CONCLUSIONS: Mutant mRNA with a c.1896G>A substitution may be diminished by NMD,
      and the resultant decrease in CACNA1C message leads to a novel mechanism for
      inducing BrS that is distinct from that reported previously.

PMID- 24321234
TI  - A wide QRS complex tachycardia: what is the mechanism?

PMID- 24321235
TI  - Inappropriate subcutaneous implantable cardioverter-defibrillator shocks due to T
      wave oversensing can be prevented: implications for management.
AB  - BACKGROUND: Inappropriate shocks (IASs) complicate implantable cardioverter
      defibrillator (ICD) therapy. The management of IASs in patients with a
      subcutaneous ICD (S-ICD) differs from that in patients with a conventional ICD
      because of different sensing algorithms and programming options. OBJECTIVE: To
      describe the management of IASs in patients with an S-ICD. METHODS: Patients were
      implanted with an S-ICD between February 2009 and July 2012. The prevalence data
      and clinical determinants of IASs were prospectively collected. In the case of T
      wave oversensing (TWOS), an exercise test was performed, and all possible sensing
      vectors were screened for TWOS. The absence of TWOS defined a suitable vector.
      RESULTS: Eleven of 69 patients (54% men; mean age 39 +/- 14 years; 73% primary
      prevention) received IASs after 8.9 +/- 10 months of implantation (10.8% annual
      incidence rate). In 8 cases, TWOS caused IASs. Seven of these IASs occurred
      during exercise and 1 during atrial fibrillation with a high ventricular rate. To
      manage TWOS, in 7 of 8 patients the sensing vector was changed and in 5 of 8
      patients the (un)conditional zone was changed. Hereafter, IASs recurred in 3 of 8
      patients, in 2 because of programming errors. Hence, after reprogramming, we
      observed no IASs in 87.5% of the patients with TWOS during a follow-up of 14.1 +/
      13 months. CONCLUSIONS: IASs due to TWOS in the S-ICD can be managed by
      reprogramming the sensing vector and/or the therapy zones of the device using a
      template acquired during exercise. Exercise-optimized programming can reduce
      future IASs, and standard exercise testing shortly after the implantation of an S
      ICD may be considered in patients at an increased risk for TWOS.

PMID- 24321236
TI  - Sequencing deeper to find the genetic mechanism of atrial fibrillation.

PMID- 24321237
TI  - Structural insight into concealed long QT type 1.

PMID- 24321238
TI  - Tissue velocity imaging of the left atrium predicts response to flecainide in
      patients with acute atrial fibrillation.
AB  - BACKGROUND: Acute atrial fibrillation (AF) is often treated with the
      administration of intravenous flecainide; however, this treatment may not always
      be successful and is potentially hazardous. Previous studies suggest that electro
      echocardiographic tissue velocity imaging (TVI) of the atrial wall may reflect
      atrial remodeling. OBJECTIVE: To study whether atrial TVI can be used to identify
      nonresponders of flecainide administered intravenously in patients with acute AF.
      METHODS: We used atrial TVI to measure atrial fibrillatory cycle length
      determined by using tissue velocity imaging (AFCL-TVI) and atrial fibrillatory
      wall motion velocity determined by using tissue velocity imaging (AFV-TVI) in the
      left atrium in 52 (55%) patients presenting with acute AF in the emergency
      department. These 2 parameters reflect electrical and structural remodeling,
      respectively. Standard baseline characteristics were recorded. RESULTS: Patients
      were predominantly men (76%) and 64 +/- 11 years old. Thirty-six (69%) patients
      had successful cardioversion after flecainide infusion. There were no significant
      differences in baseline characteristics between responders and nonresponders.
      Patients with a successful cardioversion had a longer mean AFCL-TVI and higher
      median (interquartile range) AFV-TVI compared with patients with failed
      cardioversion: 172 +/- 29 ms vs 137 +/- 35 ms (P < .001) and 4.2 (3.3-6.2) cm/s
      vs 2.3 (1.9-3.5) cm/s (P = .001). CONCLUSIONS: Electro-echocardiographic atrial
      TVI measurement is a promising noninvasive tool for predicting outcome of
      pharmacological cardioversion. A short AFCL-TVI and a low AFV-TVI are related to
      failure of cardioversion of AF using flecainide.

PMID- 24321239
TI  - Initial results of using a novel irrigated multielectrode mapping and ablation
      catheter for pulmonary vein isolation.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) as a cornerstone for catheter ablation
      of atrial fibrillation (AF) remains a complex and time-consuming procedure.
      OBJECTIVE: To assess feasibility, safety, and acute efficacy of a novel irrigated
      multielectrode ablation catheter guided by an electroanatomic mapping system for
      PVI in patients with paroxysmal AF. METHODS: Twenty-five consecutive patients (60
      +/- 10 years) with paroxysmal AF underwent PVI by using a novel decapolar mapping
      and ablation catheter (nMARQ catheter, Biosense Webster Inc, Diamond Bar, CA).
      Ablation was guided by electroanatomic mapping allowing radiofrequency (RF)
      energy delivery in the antral region of pulmonary veins (PVs) from 10 irrigated
      electrodes simultaneously. The day after ablation, cardiac magnetic resonance
      imaging was performed routinely in order to assess for potential acute PV
      stenosis. RESULTS: Overall, 97 of 97 (100%) targeted PVs could be isolated with a
      mean of 27 +/- 11 RF applications and a mean total burning time of 15 +/- 6
      minutes per patient. The total procedure time from femoral vein access to
      catheter withdrawal was 110 +/- 31 minutes, including a mean total fluoroscopy
      time of 23 +/- 9 minutes. On average, 6 +/- 3 RF impulses with a maximum of 25 W
      were applied per vein. After a short learning curve, procedure, fluoroscopy, and
      total burning times decreased to 94 +/- 16, 16 +/- 3, and 9 +/- 2 minutes,
      respectively (P < .05). Entrance and exit blocks could be verified by placing the
      ablation catheter into 90 of 97 (93%) PVs in 18 of 25 (72%) patients. No
      procedure-related complications were observed, especially no acute PV stenosis
      could be detected. CONCLUSIONS: The use of a novel irrigated multielectrode
      ablation system for PVI is feasible and safe, resulting in acute isolation of all
      targeted PVs with no complications and short procedure times. Sustainability of
      these initial results has to be confirmed in long-term efficacy and follow-up
      trials.

PMID- 24321240
TI  - Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and
      neutrophil elastase.
AB  - BACKGROUND: Tumor cells produce various cytokines and chemokines that attract
      leukocytes. Leukocytes can amplify parenchymal innate immune responses, and have
      been shown to contribute to tumor promotion. Neutrophils are among the first
      cells to arrive at sites of inflammation, and the increased number of tumor
      associated neutrophils is linked to poorer outcome in patients with lung cancer.
      RESULTS: We have previously shown that COPD-like airway inflammation promotes
      lung cancer in a K-ras mutant mouse model of lung cancer (CC-LR). This was
      associated with severe lung neutrophilic influx due to the increased level of
      neutrophil chemoattractant, KC. To further study the role of neutrophils in lung
      tumorigenesis, we depleted neutrophils in CC-LR mice using an anti-neutrophil
      antibody. This resulted in a significant reduction in lung tumor number. We
      further selectively inhibited the main receptor for neutrophil chemo-attractant
      KC, CXCR2. Similarly, this resulted in suppression of neutrophil recruitment into
      the lung of CC-LR mice followed by significant tumor reduction. Neutrophil
      elastase (NE) is a potent elastolytic enzyme produced by neutrophils at the site
      of inflammation. We crossed the CC-LR mice with NE knock-out mice, and found that
      lack of NE significantly inhibits lung cancer development. These were associated
      with significant reduction in tumor cell proliferation and angiogenesis.
      CONCLUSION: We conclude that lung cancer promotion by inflammation is partly
      mediated by activation of the IL-8/CXCR2 pathway and subsequent recruitment of
      neutrophils and release of neutrophil elastase. This provides a baseline for
      future clinical trials using the IL-8/CXCR2 pathway or NE inhibitors in patients
      with lung cancer.

PMID- 24321241
TI  - Composite pleomorphic xanthoastrocytoma-epithelioid glioneuronal tumor with BRAF
      V600E mutation - report of three cases.
AB  - We report three examples of a composite pleomorphic xanthoastrocytoma-epithelioid
      glioneuronal tumor (PXAEGT) occurring in an adolescent male and two young women.
      All were superficial and two were located in proximity to the optic nerves.
      Previously reported composite PXA-gangliogliomas (PXA-GG), have been considered
      "collision tumors" since little intermingling of the two elements has been
      present. In contrast, we hypothesized that the two elements of the PXA-EGT might
      instead derive from a common origin. To test this, we sampled the separate
      regions of these biphasic tumors and assessed each component for the BRAF V600E
      mutation, a genetic feature seen in two-thirds of pure PXAs. The BRAF mutation
      was found in both tumor areas in all cases, suggesting a common origin for the
      components, rather than a collision tumor. These biphasic PXA-EGT cases represent
      a new histomorphological combination of neuroepithelial neoplastic elements.
      These cases further expand the range of glial neoplasia in which epithelioid
      morphology is encountered, and add to the growing list of biphasic tumors
      harboring the BRAF V600E mutation. 

PMID- 24321242
TI  - Sentinel nodes identified by computed tomography-lymphography accurately stage
      the axilla in patients with breast cancer.
AB  - BACKGROUND: Sentinel node biopsy often results in the identification and removal
      of multiple nodes as sentinel nodes, although most of these nodes could be non
      sentinel nodes. This study investigated whether computed tomography-lymphography
      (CT-LG) can distinguish sentinel nodes from non-sentinel nodes and whether
      sentinel nodes identified by CT-LG can accurately stage the axilla in patients
      with breast cancer. METHODS: This study included 184 patients with breast cancer
      and clinically negative nodes. Contrast agent was injected interstitially. The
      location of sentinel nodes was marked on the skin surface using a CT laser light
      navigator system. Lymph nodes located just under the marks were first removed as
      sentinel nodes. Then, all dyed nodes or all hot nodes were removed. RESULTS: The
      mean number of sentinel nodes identified by CT-LG was significantly lower than
      that of dyed and/or hot nodes removed (1.1 vs 1.8, p <0.0001). Twenty-three
      (12.5%) patients had >=2 sentinel nodes identified by CT-LG removed, whereas 94
      (51.1%) of patients had >=2 dyed and/or hot nodes removed (p <0.0001).
      Pathological evaluation demonstrated that 47 (25.5%) of 184 patients had
      metastasis to at least one node. All 47 patients demonstrated metastases to at
      least one of the sentinel nodes identified by CT-LG. CONCLUSIONS: CT-LG can
      distinguish sentinel nodes from non-sentinel nodes, and sentinel nodes identified
      by CT-LG can accurately stage the axilla in patients with breast cancer.
      Successful identification of sentinel nodes using CT-LG may facilitate image
      based diagnosis of metastasis, possibly leading to the omission of sentinel node
      biopsy.

PMID- 24321243
TI  - Chronic periodontitis and its possible association with oral squamous cell
      carcinoma - a retrospective case control study.
AB  - INTRODUCTION: Different inflammatory processes may trigger the development of
      malignancies. Therefore, the aim of the present study was to evaluate a potential
      association between radiological determined chronic periodontitis (CPA) and oral
      squamous cell carcinoma (OSCC). METHODS: In a retrospective study, OSCC-patients
      and a control group without malignant tumors were radiographically examined for
      bone loss. Via telephone survey and questionnaire, general clinical data on the
      individual oral hygiene and concomitant diseases together with tobacco and
      alcohol use were assessed and data were compared between the groups. RESULTS: 178
      OSCC-patients and 123 controls were included. In univariate analysis, a
      statistically relevant higher mean bone loss was seen in the OSCC group (4.3 mm
      (SD: 1.8; 95% confidence interval (CI): 4-4.6) vs. 2.9 mm (SD: 0.7; 95% CI: 2.8
      3); p < 0.001)). This was confirmed in a multivariate regression model (OR: 2.4,
      95% CI: 1.5-3.8; p < 0.001). A history of periodontal treatment was associated
      with significantly reduced OSCC risk (p < 0.001; OR: 0.2, CI: 0.1-0.5).
      CONCLUSIONS: CPA is a common disease and the monitoring as well as the treatment
      of such a chronic oral inflammation may be beneficial in reducing one potential
      cause of OSCC. Therefore, further clinical studies on oral neoplasms should
      consider clinical periodontal parameters as well.

PMID- 24321244
TI  - Cathepsin K inhibitors increase distal femoral bone mineral density in rapidly
      growing rabbits.
AB  - BACKGROUND: Selective and reversible inhibitors of human Cathepsin K (CatK),
      including odanacatib (ODN), have been developed as potential therapeutics for the
      treatment of osteoporosis. Inhibitors of human CatK show significantly less
      potency for the rodent enzymes compared with that for the human or rabbit
      enzymes; thus the Schenk model in growing rabbit was developed as a screening
      assay for the in vivo activity of CatK inhibitors in blocking bone resorption.
      METHODS: In this study, the efficacy of the selective inhibitors L-833905, L
      006235, L-873724, and L-1037536 (ODN) of human CatK in the rapidly growing rabbit
      'Schenk' model (age seven weeks) was compared to vehicle, using the
      bisphosphonate, alendronate (ALN), as a positive control, to assess inhibition of
      bone resorption. An enzyme inhibition assay (EIA) and an in vitro bone resorption
      assay using rabbit osteoclasts on bovine cortical bone slices were performed to
      evaluate the potency of these CatK inhibitors. Bone mineral density of the distal
      femur (DFBMD) was measured after ten days of treatment using ex vivo DXA
      densitometry. RESULTS: Results of the EIA using rabbit CatK and the rabbit bone
      resorption assay showed that three of the four compounds (L-006235, L-873724, and
      ODN) had similar potencies in the reduction of collagen degradation. L-833905
      appeared to be a weaker inhibitor of CatK. Taking into account the respective in
      vitro potencies and pharmacokinetic profiles via oral administration, the
      efficacy of these four CatK inhibitors was demonstrated in a dose-related manner
      in the growing rabbit. Significant increases in DFBMD in animals dosed with the
      CatK inhibitors compared to vehicle were seen. CONCLUSIONS: Efficacy of the CatK
      inhibitors in the Schenk rabbit correlated well with that in the in vitro rabbit
      bone resorption assay and in the ovariectomized rabbit model as previously
      published. Hence, these studies validated the rabbit Schenk assay as a rapid and
      reliable in vivo model for prioritizing human CatK inhibitors as potential
      therapeutic agents.

PMID- 24321246
TI  - Estimation of between-trial variance in sequential meta-analyses: a simulation
      study.
AB  - Estimators for the variance between treatment effects from randomized clinical
      trials (RCTs) in a meta-analysis may yield divergent or even contradictory
      results. In a sequential meta-analysis (SMA), their properties are even more
      important, as they influence the point in time at which definite conclusions are
      drawn. In this study, we evaluated the properties of estimators of heterogeneity
      to be used in an SMA. We conducted an extensive simulation study with dichotomous
      and continuous outcome data and applied the estimators in real life examples.
      Bias and variance of the estimators were used as primary evaluation criteria, as
      well as the number of RCTs and patients from the accumulating trials needed to
      get stable estimates. The simulation studies showed that the well-known
      DerSimonian-Laird (DL) estimator largely underestimates the true value for
      dichotomous outcomes. The two-step DL (DL2) significantly improves this behavior.
      In general, the DL2 and Paule-Mandel (PM) estimators are recommended for both
      dichotomous and continuous outcome data for use in an SMA. 

PMID- 24321245
TI  - High glutamate permeability and distal localization of Best1 channel in CA1
      hippocampal astrocyte.
AB  - BACKGROUND: Glutamate is the major neurotransmitter that mediates a principal
      form of excitatory synaptic transmission in the brain. From the presynaptic
      terminals of neurons, glutamate is released upon exocytosis of the glutamate
      packaged vesicles. In recent years, astrocytes are also known to release
      glutamate via various routes to modulate synaptic transmission. In particular, we
      have characterized a glutamate-permeable Ca2+-activated anion channel encoded by
      Bestrophin 1 gene (Best1) that is responsible for Ca2+-dependent, channel
      mediated glutamate release in astrocyte. Best1 channel contains a large pore that
      is readily permeable to large molecules such as glutamate and GABA. In those
      studies we obtained permeability ratio of glutamate to Cl- in heterologously
      expressed mouse Best1 in HEK293T cells and in endogenously expressed mouse Best1
      in cultured astrocytes. However, up to now, glutamate permeability of the native
      Best1 channel in vivo has not been reported. FINDINGS: In whole-cell recordings
      of CA1 hippocampal astrocytes, we found that opening of Best1 channel upon
      activation of a Gq-coupled GPCR, protease-activated receptor 1 (PAR1) generated
      the anion current carried by glutamate via Ca2+ increase. This Ca2+-evoked
      glutamate-mediated anion current was unaffected by pretreatment of the inhibitors
      for a gap junction hemi-channel or Ca2+-activated K+ conductance. This astrocytic
      anion conductance carried by glutamate was mediated by Best1 channel expression
      in CA1 hippocampal astrocytes, because Best1 knock-down by shRNA expression
      eliminated astrocytic glutamate conductance by PAR-1 activation. However, we
      found that these astrocytes showed a deviation in reversal potential of Best1
      mediated current from the predicted value. By performing dual patch recording, we
      concluded that the deviation of reversal potential is due to incomplete space
      clamping arising from extremely leaky membrane (input resistance ranging 1-3
      MOmega), very low length constant of astrocytic processes, and the localization
      of Best1 channel in distal microdomains near synapses. Based on the relative
      shift of reversal potentials by ion substitutions, we estimated the permeability
      ratio of glutamate and Cl- (Pglutamate/PCl) as 0.53. CONCLUSIONS: Our study shows
      that Best1, located at the microdomains near the synaptic junctions, has a
      significantly high permeability to glutamate in vivo, serving as the prominent
      glutamate-releasing channel in astrocytes, mediating the release of various
      gliotransmitters in the brain, and playing an important role in modulating
      synaptic transmission.

PMID- 24321247
TI  - Removal of trace organics by anaerobic membrane bioreactors.
AB  - The biological removal of 38 trace organics (pharmaceuticals, endocrine
      disruptors, personal care products and pesticides) was studied in an anaerobic
      membrane bioreactor (AnMBR). This work presents complete information on the
      different removal mechanisms involved in the removal of trace organics in this
      process. In particular, it is focused on advanced characterization of the
      relative amount of TO accumulated within the fouling layers formed on the
      membranes. The results show that only 9 out of 38 compounds were removed by more
      than 90% while 23 compounds were removed by less than 50%. These compounds are
      therefore removed in an AnMBR biologically and partially adsorbed and retained by
      flocs and the deposition developed on the membranes, respectively. A total amount
      of 288 mg of trace organics was retained per m(2) of membrane, which were
      distributed along the different fouling layers. Among the trace organics
      analyzed, 17alpha-ethynylestradiol, estrone, octylphenol and bisphenol A were the
      most retained by the fouling layers. Among the fouling layers deposited on the
      membranes, the non-readily detachable layer has been identified as the main
      barrier for trace organics. 

PMID- 24321248
TI  - Strategic rehabilitation planning of piped water networks using multi-criteria
      decision analysis.
AB  - To overcome the difficulties of strategic asset management of water distribution
      networks, a pipe failure and a rehabilitation model are combined to predict the
      long-term performance of rehabilitation strategies. Bayesian parameter estimation
      is performed to calibrate the failure and replacement model based on a prior
      distribution inferred from three large water utilities in Switzerland. Multi
      criteria decision analysis (MCDA) and scenario planning build the framework for
      evaluating 18 strategic rehabilitation alternatives under future uncertainty.
      Outcomes for three fundamental objectives (low costs, high reliability, and high
      intergenerational equity) are assessed. Exploitation of stochastic dominance
      concepts helps to identify twelve non-dominated alternatives and local
      sensitivity analysis of stakeholder preferences is used to rank them under four
      scenarios. Strategies with annual replacement of 1.5-2% of the network perform
      reasonably well under all scenarios. In contrast, the commonly used reactive
      replacement is not recommendable unless cost is the only relevant objective.
      Exemplified for a small Swiss water utility, this approach can readily be adapted
      to support strategic asset management for any utility size and based on
      objectives and preferences that matter to the respective decision makers. 

PMID- 24321249
TI  - Validation of a simple method for predicting the disinfection performance in a
      flow-through contactor.
AB  - Despite its shortcomings, the T10 method introduced by the United States
      Environmental Protection Agency (USEPA) in 1989 is currently the method most
      frequently used in North America to calculate disinfection performance. Other
      methods (e.g., the Integrated Disinfection Design Framework, IDDF) have been
      advanced as replacements, and more recently, the USEPA suggested the Extended T10
      and Extended CSTR (Continuous Stirred-Tank Reactor) methods to improve the
      inactivation calculations within ozone contactors. To develop a method that fully
      considers the hydraulic behavior of the contactor, two models (Plug Flow with
      Dispersion and N-CSTR) were successfully fitted with five tracer tests results
      derived from four Water Treatment Plants and a pilot-scale contactor. A new
      method based on the N-CSTR model was defined as the Partially Segregated (Pseg)
      method. The predictions from all the methods mentioned were compared under
      conditions of poor and good hydraulic performance, low and high disinfectant
      decay, and different levels of inactivation. These methods were also compared
      with experimental results from a chlorine pilot-scale contactor used for
      Escherichia coli inactivation. The T10 and Extended T10 methods led to large over
      and under-estimations. The Segregated Flow Analysis (used in the IDDF) also
      considerably overestimated the inactivation under high disinfectant decay. Only
      the Extended CSTR and Pseg methods produced realistic and conservative
      predictions in all cases. Finally, a simple implementation procedure of the Pseg
      method was suggested for calculation of disinfection performance. 

PMID- 24321250
TI  - Screening level mixture risk assessment of pharmaceuticals in STP effluents.
AB  - We modeled the ecotoxicological risks of the pharmaceutical mixtures emitted from
      STP effluents into the environment. The classic mixture toxicity concept of
      Concentration Addition was used to calculate the total expected risk of the
      analytically determined mixtures, compare the expected impact of seven effluent
      streams and pinpoint the most sensitive group of species. The risk quotient of a
      single, randomly selected pharmaceutical is often more than a factor of 1000
      lower than the mixture risk, clearly indicating the need to systematically
      analyse the overall risk of all pharmaceuticals present. The MCR, which is the
      ratio between the most risky compound and the total mixture risk, varies between
      1.2 and 4.2, depending on the actual scenario and species group under
      consideration. The mixture risk quotients, based on acute data and an assessment
      factor of 1000, regularly exceed 1, indicating a potential risk for the
      environment, depending on the dilution in the recipient stream. The top 10
      mixture components explain more than 95% of the mixture risk in all cases. A
      mixture toxicity assessment cannot go beyond the underlying single substance
      data. The lack of data on the chronic toxicity of most pharmaceuticals as well as
      the very few data available for in vivo fish toxicity has to be regarded as a
      major knowledge gap in this context. On the other hand, ignoring Independent
      Action or even using the sum of individual risk quotients as a rough
      approximation of Concentration Addition does not have a major impact on the final
      risk estimate. 

PMID- 24321252
TI  - Allergen-induced production of IL-31 by canine Th2 cells and identification of
      immune, skin, and neuronal target cells.
AB  - The canine cytokine IL-31 induces pruritus in dogs and can be detected in dogs
      with atopic dermatitis; however very little is understood around its interactions
      with specific canine cells. We hypothesize that IL-31 is involved in the
      progression of allergic skin disease by coordinating the interaction between the
      immune system with skin and neuronal systems. The goal of the following work was
      to identify cells that produce IL-31 as well as cells that may respond to this
      cytokine. Peripheral blood mononuclear cells (PBMCs) were collected from naive
      and house dust mite (HDM) allergen-sensitized beagle dogs and used for ex vivo
      characterization of cytokine production assessed using ELISpot and quantitative
      immunoassay. Sensitization to HDM allergen induced a T-helper type 2 (Th2) cell
      phenotype characterized by an increase in the production of IL-4 protein.
      Interestingly, repeated allergen challenge over time also resulted in an increase
      in IFN-gamma. Further evaluation showed that co-stimulation of Th2 polarized
      cells with antigen and the bacterial component Staphylococcus enterotoxin B (SEB)
      produced higher levels of IL-31 compared to either stimulant alone. Production of
      IL-31 when PBMCs were stimulated by T cell mitogens suggests T cells as a source
      of IL-31. Quantitative real-time PCR was utilized to determine expression of the
      IL-31 receptor alpha chain in canine cell lines and tissue. Canine monocytic
      cells, keratinocytes, and dorsal root ganglia were shown to express the IL-31
      receptor alpha chain mRNA. In a multifaceted disease such as canine atopic
      dermatitis, the combination of Th2 polarization and microbial presence may lead
      to IL-31 mediated effects driving inflammation and pruritus by immune cells,
      keratinocytes, and direct neuronal stimulation.

PMID- 24321251
TI  - Galectin-9 prolongs the survival of septic mice by expanding Tim-3-expressing
      natural killer T cells and PDCA-1+ CD11c+ macrophages.
AB  - INTRODUCTION: Galectin-9 ameliorates various inflammatory conditions including
      autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC)
      functions. However, the effect of galectin-9 on polymicrobial sepsis has not been
      assessed. METHODS: We induced polymicrobial sepsis by cecal ligation and puncture
      (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated
      CLP mice. An ELISA was used to compare the levels of various cytokines in the
      plasma and culture supernatants. Fluorescence-activated cell sorting analysis was
      further performed to compare the frequencies of subpopulations of spleen cells.
      RESULTS: Galectin-9 exhibited a protective effect in polymicrobial sepsis as
      demonstrated in galetin-9 transgenic mice and therapeutic galectin-9
      administration. In contrast, such effect was not observed in nude mice,
      indicating the involvement of T cells in galectin-9-mediated survival
      prolongation. Galectin-9 decreased TNFalpha, IL-6, IL-10 and, high mobility group
      box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9
      increased the frequencies of natural killer T (NKT) cells and PDCA-1+ CD11c+
      macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8
      T cells, gammadeltaT cells or conventional DC. As expected, galectin-9 decreased
      the frequency of Tim-3+ CD4 T cells, most likely Th1 and Th17 cells.
      Intriguingly, many spleen NK1.1+ NKT cells and pDC-like macrophages expressed Tim
      3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1+ NKT cells and
      pDC-like macrophages. Galectin-9 further increased IL-17+ NK1.1+ NKT cells.
      CONCLUSION: These data suggest that galectin-9 exerts therapeutic effects on
      polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages
      and by modulating the production of early and late proinflammatory cytokines.

PMID- 24321253
TI  - The prostate-specific membrane antigen: lessons and current clinical implications
      from 20 years of research.
AB  - OBJECTIVE: Despite a multitude of detection and treatment advances in the past 2
      decades, prostate cancer remains the second leading cause of deaths due to cancer
      among men in the United States. Technological evolution and expanding knowledge
      of tumor biomarkers have invigorated exploration in prostate cancer therapeutics.
      Prostate-specific membrane antigen (PSMA) was one of the first prostate cancer
      biomarkers successfully cloned. Since then, it has been characterized as the
      prototypical cell-surface marker for prostate cancer and has been the subject of
      intense clinical inquiry. In this article, we review the relevant research in
      PSMA on the 20th anniversary of its cloning. METHODS AND MATERIALS: A PubMed
      search using the keywords "prostate-specific membrane antigen" or "glutamate
      carboxypeptidase II" provided 1019 results. An additional 3 abstracts were
      included from scientific meetings. Articles were vetted by title and abstract
      with emphasis placed on those with clinically relevant findings. RESULTS: Sixty
      articles were selected for inclusion. PSMA was discovered and cloned in 1993. Its
      structure and function were further delineated in the ensuing decade. Consensus
      sites of expression in normal physiology are prostate, kidney, nervous system,
      and small intestine. PSMA has been implicated in the neovasculature of several
      tumors including urothelial and renal cell carcinomas. In prostate cancer,
      expression of PSMA is directly related to the Gleason grade. PSMA has been tested
      both in imaging and therapeutics in a number of prostate cancer clinical trials.
      Several recent approaches to target PSMA include the use of small molecule
      inhibitors, PSMA-based immunotherapy, RNA aptamer conjugates, and PSMA-targeted
      prodrug therapy. Future study of PSMA in prostate cancer might focus on its
      intracellular functions and possible role in tumor neurogenesis. CONCLUSIONS:
      Twenty years from its discovery, PSMA represents a viable biomarker and treatment
      target in prostate cancer. Research to delineate its precise role in prostate
      carcinogenesis and within the therapeutic armamentarium for patients with
      prostate cancer remains encouraging.

PMID- 24321254
TI  - Essential elements of personalized medicine.
AB  - OBJECTIVES: Genomic information has been promoted as the basis for "personalized"
      health care. We considered the benefits provided by genomic testing in context of
      the concept of personalized medicine. MATERIALS AND METHODS: We evaluated current
      and potential uses of genomic testing in health care, using prostate cancer as an
      example, and considered their implications for individualizing or otherwise
      improving health care. RESULTS AND CONCLUSIONS: Personalized medicine is most
      accurately seen as a comprehensive effort to tailor health care to the
      individual, spanning multiple dimensions. While genomic tests will offer many
      potential opportunities to improve the delivery of care, including the potential
      for genomic research to offer opportunities to improve prostate cancer screening
      and treatment, such advances do not in themselves constitute a paradigm shift in
      the delivery of health care. Rather, personalized medicine is based on a
      partnership between clinician and patient that utilizes shared decision making to
      determine the best health care options among the available choices, weighing the
      patient's personal values and preferences together with clinical findings. This
      approach is particularly important for difficult clinical decisions involving
      uncertainty and trade-offs, such as those involved in prostate cancer screening
      and management. The delivery of personalized medicine also requires adequate
      health care access and assurance that basic health needs have been met.
      Substantial research investment will be needed to identify how genomic tests can
      contribute to this effort.

PMID- 24321255
TI  - A cross-sectional investigation of fatigue in advanced renal cell carcinoma
      treatment: results from the FAMOUS study.
AB  - OBJECTIVE: With an increasing choice of new treatment options, the management of
      side effects to maintain a chosen treatment if likely to be effective on the
      tumor remains important. The perception of side effects however varies between
      the physician and the patient, leading to possible wrong assumptions on
      tolerability that result in dose modifications, which may ultimately affect
      effectiveness. The aim was to assess fatigue in patients with advanced or
      metastatic renal cell carcinoma (RCC) by comparing the evaluation of the
      physician to the one provided by their respective patient. In addition, we aimed
      to assess possible influences of fatigue on parameters of quality of life.
      METHODS: Patients receiving systemic treatment for advanced RCC and their
      physicians were questioned independently regarding incidence and severity of
      fatigue and its effect on quality of life. RESULTS: Both physicians and patients
      completed 98 matching questionnaires. Patients were treated with sunitinib,
      sorafenib, bevacizumab combined with interferon alpha, temsirolimus, everolimus,
      or interferon alpha alone. Incidence and severity of fatigue was differently
      assessed by patients and physicians, with fatigue being more severe when reported
      by the patient. The severity of fatigue increased with progressing treatment
      lines. Quality of life was significantly lower in patients experiencing fatigue
      compared with patients without fatigue. Emotional, functional, and physical well
      being were all affected by fatigue, the latter being the most affected subscale.
      Social well-being was least affected. CONCLUSION: Fatigue is a complex and
      cumulative condition of patients treated for advanced RCC, and it considerably
      affects patient's quality of life. As many of its underlying causes may be
      treated, the divergent perception of occurrence and severity of fatigue should be
      integrated in treatment concepts. The active role of the patient in helping to
      manage ailments through assessment should be implemented when optimizing
      treatment of RCC.

PMID- 24321256
TI  - Clinical prognostic factors associated with outcome in patients with renal cell
      cancer with prior tyrosine kinase inhibitors or immunotherapy treated with
      everolimus.
AB  - BACKGROUND: The mTOR inhibitor, everolimus, is approved for the treatment of
      metastatic renal cell carcinoma (RCC). However, prognostic models are needed to
      determine the patients who would most benefit from this therapy. We have
      developed a model based on clinical parameters and patient stratification into
      risk groups to predict patients with RCC who will derive the most benefit from
      treatment with everolimus. METHODS: We assessed retrospective data on 57 patients
      with RCC who received everolimus after previous treatment with immunotherapy or
      tyrosine kinase inhibitors to identify prognostic factors for progression-free
      survival (PFS) and overall survival (OS). In the original phase II study,
      patients received 10mg of everolimus daily without interruption and were assessed
      every other week for the first 8 weeks on therapy and every 4 weeks thereafter.
      Kaplan-Meier analysis was used to calculate OS and PFS. Univariate and
      multivariate analyses were constructed using the Cox proportional hazards model
      and a stepwise procedure to validate the data. RESULTS: We grouped patients
      according to risk: 0 prognostic factors indicated favorable risk, 1 to 2 factors
      intermediate risk, and>=3 factors poor risk. We found notable differences in
      median OS (29.6 mo for favorable risk, 14.3 mo for intermediate risk, and 7.2 mo
      for poor risk). Three risk factors (prior radiation treatment, no lung metastasis
      present at the start of treatment, and lymphocytes<25cells/ul) in the
      multivariate analysis were found to be associated with PFS, and 4 risk factors
      were found to be associated with OS (bone metastasis at start of treatment,
      LDH>1.5*upper limit of normal, alkaline phosphatase>120U/l, and
      lymphocytes<25cells/ul). CONCLUSIONS: Our prognostic model includes 3 readily
      available clinical parameters for PFS and 4 readily available clinical parameters
      for OS to help stratify patients into poor, intermediate, and favorable prognosis
      groups for the treatment of everolimus in clear cell RCC. These intriguing
      results warrant further study in a larger patient population to validate the
      findings.

PMID- 24321257
TI  - Clinical and laboratory prognostic factors in patients with metastatic renal cell
      carcinoma treated with sunitinib and sorafenib after progression on cytokines.
AB  - OBJECTIVES: The aim of this retrospective study was to analyze prognostic factors
      in patients with metastatic renal cell carcinoma treated with tyrosine kinase
      inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy.
      MATERIALS AND METHODS: A national database of patients treated with targeted
      agents was used as the data source. A total of 319 patients treated with
      sunitinib (n = 181) or sorafenib (n = 138) after progression on cytokine therapy
      were analyzed. RESULTS: Prognostic factors significantly associated with poor
      overall survival in a multivariable Cox model included the time from diagnosis to
      the start of treatment with TKIs<1 year, increased neutrophil counts, increased
      lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status
      2 or higher. The parameters showing statistically significant association with
      progression-free survival included time from diagnosis to the beginning of
      treatment with TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology
      Cooperative Group performance status 2 or higher. We have also validated the
      International Metastatic Renal Cell Carcinoma Database Consortium prognostic
      model in our cohort of patients. CONCLUSION: We demonstrate that the
      International Database Consortium prognostic model performs well for European
      patients treated with TKIs, including sunitinib or sorafenib, after progression
      on cytokines and suggest that a reduction from original 6 down to 4 parameters is
      possible.

PMID- 24321258
TI  - Outcomes in patients with metastatic renal cell cancer treated with
      individualized sunitinib therapy: correlation with dynamic microbubble ultrasound
      data and review of the literature.
AB  - BACKGROUND: Increased sunitinib exposure (area under the curve) is associated
      with better outcome in metastatic renal cell cancer. Recommendations for dose
      modification do not take this into account. A treatment strategy, based on
      individual patient toxicity, was developed to maximize dose and minimize time
      without therapy for patients who could not tolerate the standard sunitinib
      schedule of 50mg given for 28 days with a 14-day break (50mg, 28/14). METHODS: A
      single-center retrospective review was conducted on patients with metastatic
      renal cell cancer treated from October 2005 to March 2010. Dose/schedule
      modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and
      gastrointestinal) at <= grade 2. DSM-1 was 50mg, 14 days on/7 days off with
      individualized increases in days on treatment. DSM-2 was 50mg, 7 days on/7 days
      off with individualized increase in days on treatment. DSM-3 was 37.5mg with
      individualized 7-day breaks. DSM-4 was 25mg with individualized 7-day breaks.
      Multivariable analysis was performed for outcome as a function of patient and
      treatment variables. RESULTS: Overall, 172 patients were included in the
      analysis. Most patients had clear cell histology (79.1%) with sunitinib given as
      a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a
      progression-free survival (PFS) (10.9-11.9 mo) and overall survival (OS) (23.4
      24.5 mo) that was significantly better than the PFS (5.3 mo; P<0.001) and OS
      (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50mg, 28/14). DCE-US in
      a subset of patients showed that maximum antiangiogenic activity was achieved
      after 14 days on therapy. CONCLUSIONS: Individualized sunitinib scheduling based
      on toxicity may improve PFS and OS. This hypothesis is supported by several other
      respective data that are reviewed. A confirmatory prospective trial is ongoing.

PMID- 24321259
TI  - Optimal timing of early versus delayed adjuvant radiotherapy following radical
      prostatectomy for locally advanced prostate cancer.
AB  - OBJECTIVES: Although post-radical prostatectomy (RP) adjuvant radiation therapy
      (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing
      remains unknown. Our objective is to characterize the outcomes and optimal timing
      of early vs. delayed ART. MATERIALS AND METHODS: From the Surveillance,
      Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963
      men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4
      12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we
      compared overall mortality, prostate cancer-specific mortality (PCSM), bone
      related events (BRE), salvage hormonal therapy utilization, and intervention for
      urethral stricture. We then used the maximal statistic approach to determine at
      what time post-RP ART had the most significant effect on outcomes of interest in
      men with pT3N0 disease. RESULTS: When compared with delayed ART in men with pT3
      disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per
      100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59
      events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is
      associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is
      associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated
      higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after
      9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042).
      CONCLUSION: Initiating ART less than 5 months after RP for pT3 is associated with
      improved PCSM. Early ART is also associated with fewer BRE and less use of
      salvage hormonal therapy if administered earlier than 3 and 4 months after RP,
      respectively. However, ART administered later than 9 months after RP is
      associated with fewer urethral strictures. Our population-based findings
      complement randomized trials designed with fixed ART timing.

PMID- 24321261
TI  - Surgery for early-stage lung cancer: post-operative 30-day versus 90-day
      mortality and patient-centred care.

PMID- 24321260
TI  - Policy statement on multidisciplinary cancer care.
AB  - BACKGROUND: Cancer care is undergoing an important paradigm shift from a disease
      focused management to a patient-centred approach, in which increasingly more
      attention is paid to psychosocial aspects, quality of life, patients' rights and
      empowerment and survivorship. In this context, multidisciplinary teams emerge as
      a practical necessity for optimal coordination among health professionals and
      clear communication with patients. The European Partnership for Action Against
      Cancer (EPAAC), an initiative launched by the European Commission in 2009,
      addressed the multidisciplinary care from a policy perspective in order to define
      the core elements that all tumour-based multidisciplinary teams (MDTs) should
      include. To that effect, a working group conference was held in January 2013
      within the EPAAC Work Package 7 (on Healthcare) framework. METHODS: The consensus
      group consisted of high-level representatives from the following European
      scientific societies, patient associations and stakeholders: European CanCer
      Organisation (ECCO), European SocieTy for Radiology & Oncology (ESTRO), European
      Society for Medical Oncology (ESMO), European Society of Surgical Oncology
      (ESSO), International Society of Geriatric Oncology (SIOG), European Association
      for Palliative Care (EAPC), European Oncology Nursing Society (EONS),
      International Psycho-Oncology Society (IPOS),European Cancer Patient Coalition
      (ECPC), EuropaColon, Europa Donna - The European Breast Cancer Coalition,
      Association of European Cancer Leagues (ECL), Organisation of European Cancer
      Institutes (OECI), EUSOMA - European Society of Breast Cancer Specialists,
      European Hospital and Healthcare Federation (HOPE) and EPAAC Work Packages 5
      (Health promotion and prevention), 7, 8 (Research), 9 (Information systems) and
      10 (Cancer plans). A background document with a list of 26 core issues drawn from
      a systematic review of the literature was used to guide the discussion. Five
      areas related to MDTs were covered: care objectives, organisation, clinical
      assessment, patients' rights and empowerment and policy support. Preliminary
      drafts of the document were widely circulated for consultation and amendments by
      the working group before final approval. RESULTS: The working group unanimously
      formulated a Policy Statement on Multidisciplinary Cancer Care to define the core
      elements that should be implemented by all tumour-based MDTs. This document
      identifies MDTs as the core component in cancer care organisation and sets down
      the key elements to guide changes across all European health systems. CONCLUSION:
      MDTs are an essential instrument of effective cancer care policy, and their
      continued development crucial to providing patients the care they need and
      deserve. While implementation must remain in local hands, European health systems
      can still benefit from having a basis for an effective multidisciplinary model of
      cooperation. This policy statement is intended to serve as a reference for
      policymakers and healthcare providers who wish to improve the services currently
      provided to the cancer patients whose lives and well-being depend on their
      action.

PMID- 24321262
TI  - Small renal cell carcinomas--how dangerous are they really? Results of a large
      multicenter study.
AB  - AIM OF THE STUDY: Modern diagnostic ultrasound and cross-sectional imaging has
      enabled the detection of increasing numbers of renal tumours. The aim of this
      study was to investigate the tumour- and patient-specific characteristics and
      prognosis of small renal cell carcinomas (RCCs) after surgical resection.
      METHODS: The study included 2197 patients who underwent surgical resection of
      histologically confirmed RCC ? 4 cm between 1990 and 2011. Median (mean) follow
      up was 56.2 (65.5) months. RESULTS: At the time of surgery, tumours were staged
      as pT ? 3a in 175 (8.0%) cases, 134 (6.2%) were poorly differentiated and 75
      (3.5%) were metastasised. The larger the tumour size, the higher was the risk of
      presenting with stage pT ? 3a (p<0.001), poor tumour differentiation (p = 0.004),
      microscopic vascular involvement (p = 0.001) and collecting system invasion (p =
      0.03). The 5-year cancer-specific survival (CSS) rate was 93.8% for stage pT1a
      versus 79.4% for stage pT ? 3a (p<0.001), and it was 93.7% for G1-2 versus 76.8%
      for G3-4 differentiation (p<0.001). Multivariate analysis identified age in years
      (hazard ratio (HR) 1.04, p<0.001), metastatic disease (HR 12.5, p < 0.001),
      tumour differentiation (HR 2.8, p<0.001) and non-clear cell histology (HR 0.51, p
      = 0.02) as independent prognosticators for CSS in patients with small RCC.
      Interestingly, the 5-year cancer-specific mortality rate for pT1a N/M0 patients
      was 5.8%. CONCLUSIONS: This large multicenter study has clearly shown that,
      though most small RCC have a low pathological stage and a good prognosis, there
      is also a small but significant subgroup of these tumours that are already
      locally advanced or poorly differentiated.

PMID- 24321264
TI  - Genotoxicity of silver and titanium dioxide nanoparticles in bone marrow cells of
      rats in vivo.
AB  - Although nanomaterials have the potential to improve human life, their sideline
      effects on human health seem to be inevitable and still remain unknown. This
      study aimed to investigate the cytotoxicity and genotoxicity of titanium dioxide
      (TiO2) and silver (Ag) nanoparticles (NPs) at different doses and particle sizes
      to bone marrow cells. Both types of nanoparticles were chosen due to their wide
      applications of them in consumer products. Rats were injected intravenously with
      a single dose of 5 or 10 mg/kg bw of 20 nm AgNPs or with 5 mg/kg bw 200 nm AgNPs
      or with 5 mg/kg bw 21 nm TiO2NPs. The samples were taken at 24 h, 1 week and 4
      weeks following the exposure. Micronucleus test and the Comet assay were used to
      detect DNA damage. Neither AgNPs nor TiO2NPs caused cytotoxicity to bone marrow
      red and white cells. The polychromatic erythrocytes are the main target of both
      nanoparticles. A single exposure to AgNPs induced significantly enhanced
      frequency of micronuclei not only at 24 h after exposure, but also 1 and 4 weeks
      later, whereas single exposure to TiO2NPs showed positive effect at 24 h only.
      Negative responses were shown in reticulocytes (micronuclei) and in leukocytes
      (Comet assay) of bone marrow. Results indicated that different bone marrow cells
      display different susceptibility toward genotoxicity mediated by both
      investigated nanoparticles. The use of materials containing nanoparticles and the
      potential health implication of them should be monitored.

PMID- 24321263
TI  - Newly-derived neuroblastoma cell lines propagated in serum-free media
      recapitulate the genotype and phenotype of primary neuroblastoma tumours.
AB  - Recently protocols have been devised for the culturing of cell lines from fresh
      tumours under serum-free conditions in defined neural stem cell medium. These
      cells, frequently called tumour initiating cells (TICs) closely retained
      characteristics of the tumours of origin. We report the isolation of eight newly
      derived neuroblastoma TICs from six primary neuroblastoma tumours and two bone
      marrow metastases. The primary tumours from which these TICs were generated have
      previously been fully typed by whole genome sequencing (WGS). Array comparative
      genomic hybridisation (aCGH) analysis showed that TIC lines retained essential
      characteristics of the primary tumours and exhibited typical neuroblastoma
      chromosomal aberrations such as MYCN amplification, gain of chromosome 17q and
      deletion of 1p36. Protein analysis showed expression for neuroblastoma markers
      MYCN, NCAM, CHGA, DBH and TH while haematopoietic markers CD19 and CD11b were
      absent. We analysed the growth characteristics and confirmed tumour-forming
      potential using sphere-forming assays, subcutaneous and orthotopic injection of
      these cells into immune-compromised mice. Affymetrix mRNA expression profiling of
      TIC line xenografts showed an expression pattern more closely mimicking primary
      tumours compared to xenografts from classical cell lines. This establishes that
      these neuroblastoma TICs cultured under serum-free conditions are relevant and
      useful neuroblastoma tumour models. 

PMID- 24321265
TI  - Endovascular management of radiotherapy-induced injury to brachiocephalic artery
      using covered stents.
AB  - Actinic vascular lesions tend to be stenotic-occlusive lesions. In this article,
      we present 2 exceptional cases of pseudoaneurysms caused by radionecrosis of the
      supra-aortic trunks. Both patients were treated by a retrograde carotid approach
      and deployment of a self-expanding covered stent. Proper exclusion of the
      pseudoaneurysm was attained in both cases; the first patient remained
      asymptomatic 12 months later; the second patient died of mediastinitis. Compared
      with conventional surgery, endovascular management is a viable, less invasive
      alternative in select patients, especially in life-threatening cases.

PMID- 24321267
TI  - Recurrent hematuria caused by nutcracker syndrome.
AB  - A 26-year-old woman presented to the emergency department complaining of left
      flank pain, and proteinuria and hematuria were detected during urinalysis. A
      renal ultrasound did not reveal any disorder, and after performing a computed
      tomography angiography scan, compression of the left renal vein between the
      superior mesenteric artery and the aorta was seen. This compression is known as
      Nutcracker syndrome. From among the different treatment options available, it was
      decided, with patient consensus, to use open surgical management, performing a
      transposition of the left renal vein to a more distal level in the inferior vena
      cava. The immediate postoperative care progressed without complications and the
      symptoms resolved; after 1 year of surveillance, the patient continues to be
      asymptomatic. Nutcracker syndrome is a rare phenomenon, with few cases described.
      There are different therapeutic options for the treatment of Nutcracker syndrome,
      such as open surgery, endovascular treatment, or conservative treatment; because
      of the low prevalence of this syndrome, there are no sufficiently large series at
      present or with the necessary long-term surveillance to decide on the most
      suitable treatment. Distal transposition of the left renal vein in the inferior
      cava vein has proved to offer good long-term results, and this option offers a
      higher chance of resolution without the need for as many postsurgery controls as
      would be required with endovascular treatment. 

PMID- 24321266
TI  - Carotid endarterectomy national trends over a decade: does sex matter?
AB  - BACKGROUND: The objective was to evaluate the difference in timing (if any) of in
      hospital carotid endarterectomy (CEA) or outcomes of CEA based on sex among men
      and women hospitalized for carotid artery disease. METHODS: This was a
      retrospective cross-sectional study using the Nationwide Inpatient Sample
      Database. All patients from 2000-2009 who underwent CEA during their
      hospitalization were examined. International Classification of Diseases, 9th
      revision codes were used to identify patients who underwent CEA during
      hospitalization, stratify asymptomatic and symptomatic patients, determine time
      in days from admission to CEA, and examine in-hospital complications, including
      perioperative stroke, cardiac events, and death. Statistical analysis was
      performed with chi-squared and t-tests. Linear and logistic regression models
      were used to evaluate relationships between sex and outcomes. The main outcome
      measures were time from admission to surgery, in-hospital mortality,
      complications, mean duration of stay, and discharge disposition. RESULTS: Two
      hundred twenty-one thousand two hundred fifty three patients underwent CEA during
      hospitalization. More than 9% (9.2%) had symptomatic carotid artery disease.
      Among symptomatic patients, bivariate analysis found that women had a longer mean
      time from admission to surgery (2.8 vs. 2.6 days; P < 0.001) and a longer
      duration of hospital stay (6.4 vs. 5.9 days; P < 0.001) than their male
      counterparts. However, there was no difference between men and women with regard
      to rates of perioperative stroke, cardiac complications, myocardial infarction,
      or death. Among asymptomatic patients, women had a longer mean time from
      admission to surgery (0.53 vs. 0.48 days; P < 0.001) and a trend toward increased
      perioperative stroke (0.6% vs. 0.5%; P = 0.06), but a lower rate of cardiac
      complications (1.5% vs. 1.7%; P = 0.01) and in-hospital mortality (0.26% vs.
      0.31%; P = 0.05). However, on multivariable analysis adjusting for differences in
      age, elective status, insurance, race, hospital location, hospital region, and
      hospital teaching status, there was no sex disparity in time from admission to
      surgery, regardless of symptomatic status. In addition, asymptomatic women were
      less likely than men to have a cardiac complication (odds ratio [OR]: 0.90; 95%
      confidence interval [CI]: 0.83-0.97) or in-hospital mortality (OR: 0.83; 95% CI:
      0.70-0.98). Symptomatic women were also less likely than men to have a cardiac
      complication (OR: 0.78; 95% CI: 0.63-0.97). CONCLUSIONS: In this decade-long
      national population-based study of hospitalized patients undergoing CEA, women
      had lower perioperative cardiac morbidity and mortality rates than men. After
      adjusting for patient, clinical, and hospital factors, there is no discernible
      difference in timing of CEA based on sex.

PMID- 24321268
TI  - Complex renal artery aneurysm managed with hand-assisted laparoscopic
      nephrectomy, ex vivo repair, and autotransplantation.
AB  - A 58-year-old woman had an incidentally found complex right renal artery aneurysm
      (RAA) during a clinical work-up for diverticulitis. The aneurysm measured 2.5 cm
      in diameter and was located at the right renal artery bifurcation. She was
      hospitalized and underwent hand-assisted laparoscopic nephrectomy with ex vivo
      repair of the RAA and autotransplantation into the right iliac fossa. The same
      incision was used to remove the kidney from the retroperitoneum as was used to
      transplant into the right lower quadrant. She tolerated the procedure well. Her
      postoperative course was uncomplicated. Hand-assisted laparoscopic nephrectomy
      with ex vivo repair of a complicated RAA and autotransplantation is feasible and
      safe.

PMID- 24321269
TI  - Isolation of adipose tissue mesenchymal stem cells without tissue destruction: a
      non-enzymatic method.
AB  - The conventional enzymatic method is widely used for mesenchymal stem cells
      (MSCs) isolation from adipose tissue. The method holds major drawbacks; it is
      costly, time-consuming and results in a heterogeneous cell population. Besides,
      digestion of extracellular matrix causes cell injury and compromise proliferation
      and differentiation of the cells. Also, because of over handling the samples are
      also prone to contamination. Here, we introduce a non-enzymatic method for MSCs
      isolation without disturbing the cells habitat. Small pieces of adipose tissue
      obtained from animal or human liposuction were explanted into a culture flask,
      immobilized by fetal bovine serum (FBS) and incubated overnight. The explants
      were then irrigated with DMEM containing FBS. Within few days, the fibroblast
      like cells migrated from the tissue and proliferated rapidly. When subconfluent,
      the cells were harvested, expanded through 3 passages and used for
      immunophenotyping and differentiation assays. As judged by flow cytometric
      analysis of surface markers (CD44(+), CD105(+), CD34(-), CD45(-)), Oil Red O and
      Alizarin Red staining, the MSCs isolated by our non-enzymatic method were
      pluripotent and exhibited the potential for differentiation into adipocyte and
      osteoblast. Great isolation yields, homogeneity of isolated cells, brief
      procedure, and high economy are the advantages of our method over the
      conventional protocol. 

PMID- 24321271
TI  - Functional interplay between stimulus-oriented and stimulus-independent attending
      during a prospective memory task.
AB  - Recent studies have suggested that medial (medBA10) and lateral (latBA10)
      portions of the Brodmann area 10 subserve respectively stimulus-oriented (SO) and
      stimulus-independent (SI) attending during prospective memory (PM) tasks. We
      investigated this dissociation by manipulating the saliency (SO) and the memory
      load (SI) of PM cues. Sixteen healthy subjects participated to a functional
      imaging protocol with a 2*2*2 experimental design, including the factors: task
      (ongoing target vs. PM cue), Saliency (high vs. low; with targets/cues either
      embedded or standing out from distracters), and memory load (high vs. low; with 1
      or 4 possible PM targets). We localized the medBA10 and latBA10 by means of a
      localizer task. In medBA10 we found a significant main effects of high Saliency
      and low memory load; whereas in the left latBA10, we found a significant
      task*load interaction, with maximal activation for PM cues presented in the high
      load condition. These results are in agreement with the gateway hypothesis:
      during a PM task medBA10 biases attention toward external salient stimuli, SO
      attending, while latBA10 biases attention toward internal mnemonic
      representations, SI attending. Additional whole-brain analyses highlighted
      activation of other areas besides BA10, consistent with recent proposals that
      emphasise the role of distributed networks during PM performance. 

PMID- 24321270
TI  - A TrkB-STAT3-miR-204-5p regulatory circuitry controls proliferation and invasion
      of endometrial carcinoma cells.
AB  - BACKGROUND: We previously identified TrkB as an oncogene involved in promoting
      metastasis in endometrial carcinoma (EC). Here, we sought to delineate the effect
      of changes in TrkB expression on the global profile of microRNAs (miRNAs) in EC
      cells and further investigated the correlation between the expression of certain
      miRNA and TrkB in the clinicopathologic characteristics of EC patients. METHODS
      AND RESULTS: Using quantitative reverse transcription-PCR (qRT-PCR), we found
      that expression of TrkB mRNA has no significant difference in transcript levels
      between normal endometrium and EC cells captured by laser capture
      microdissection, while immunohistochemistry results demonstrated a markedly
      higher expression of TrkB protein in EC tissues. The microRNA array showed that
      ectopic overexpression and knockdown of TrkB expression caused global changes in
      miRNA expression in EC cells. qRT-PCR results showed that elevated TrkB repressed
      miR-204-5p expression in EC cells. Furthermore, immunoblotting assays revealed
      that TrkB overexpression in IshikawaTrkB cells noticeably increased JAK2 and
      STAT3 phosphorylation, which, however, was aborted by TrkB knockdown in HEC
      1BshTrkB cells. Moreover, ChIP assays showed that phospho-STAT3 could directly
      bind to STAT3-binding sites near the TRPM3 promoter region upstream of miR-204
      5p. Interestingly, using bioinformatics analysis and luciferase assays, we
      identified TrkB was a novel target of miR-204-5p. Functionally, the MTT assays,
      clonogenic and Transwell assays showed that miR-204-5p significantly suppressed
      the clonogenic growth, migration and invasion of EC cells. Furthermore, miR-204
      5p also inhibited the growth of tumor xenografts bearing human EC cells.
      Importantly, we found lower miR-204-5p expression was associated with advanced
      FIGO stages, lymph node metastasis and probably a lower chance for survival in EC
      patients. CONCLUSIONS: This study uncovers a new regulatory loop involving
      TrkB/miR-204-5p that is critical to the tumorigenesis of EC and proposes that
      reestablishment of miR-204-5p expression could be explored as a potential new
      therapeutic target for this disease.

PMID- 24321272
TI  - Multiple thalamo-cortical disconnections in anterior thalamic infarction:
      implications for thalamic mechanisms of memory and language.
AB  - Amnesia and linguistic deficits that are associated with thalamic damage have
      attracted the attention of researchers interested in identifying the neural
      networks involved in memory and language. The Papez circuit, which is composed of
      the hippocampus, mammillary body and anterior thalamic nuclei, was first proposed
      to be critical for memory. However, subsequently, the roles of the neural circuit
      consisting of the rhinal/parahippocampal cortices and the mediodorsal thalamic
      nuclei became evident. The ventral lateral nuclei or its adjacent structures have
      been found to be involved in semantic processing, but the specific neural
      circuits dedicated to language functions have not been identified. Anterior
      thalamic infarcts, which affect very circumscribed regions of the ventral
      anterior portion of the thalamus, often cause paradoxically prominent memory and
      language deficits. We conducted tractography analyses in 6 patients with left
      anterior thalamic infarcts to identify neural connections or circuits in which
      disruptions are associated with memory and language deficits in this condition.
      The current study demonstrated that the mammillothalamic tract, which connects
      the mammillary body with the anterior thalamic nuclei, and the anterior and
      inferior thalamic peduncles, which contain neural fibers that extend from several
      thalamic nuclei to the anterior temporal, medial temporal and frontal cortices,
      are disrupted in anterior thalamic infarction. These extensive thalamo-cortical
      disconnections appear to be due to the dissection of the neural fibers that
      penetrate the ventral anterior nucleus of the thalamus. Our results suggest the
      following: (1) amnesia that is associated with anterior thalamic infarction is
      best interpreted in the context of dual/multiple-system theories of
      memory/amnesia that posit that multiple neural circuits connecting the anterior
      and mediodorsal thalamic nuclei with the hippocampus and rhinal/parahippocampal
      cortices work in concert to support memory function; and (2) the semantic
      deficits observed in this syndrome may be associated with thalamo-anterior
      temporal and thalamo-lateral frontal disconnections. 

PMID- 24321274
TI  - StrainInfo introduces electronic passports for microorganisms.
AB  - Microbiology builds upon biological material deposited in biological resource
      centers (BRCs) as a reference framework for collaborative research. BRCs assign
      so-called strain numbers to label the deposited material and are responsible for
      long-term preservation and worldwide distribution of the material. Cultured
      microorganisms can be deposited into multiple BRCs and BRCs also mutually
      exchange their holdings. As a result, many different strain numbers can be
      attached to biological material that stems from the same isolate. In practice,
      this material is considered equivalent and used interchangeably. This implies
      that finding information on given biological material requires all equivalent
      strain numbers to be used when searching. StrainInfo introduces strain passports
      for microorganisms: a uniform overview of information known about a given
      microbial strain. It contains all known equivalent strain numbers and information
      on the exchange history, sequences and related literature of the strain. Each
      passport has an associated strain browser that gives direct access to the
      underlying BRC catalog entries on which the passport was based. Taxon, sequence
      and literature passports are implemented in a similar manner. In addition to web
      pages that serve human users, integrated information is also offered in machine
      readable formats useful for automated, large-scale analysis. StrainInfo is
      envisioned to be an open platform integrating microbial information. This
      platform can form the basis for new methods of microbiological research,
      leveraging the vast amount of electronic information available online. StrainInfo
      is available from http://www.StrainInfo.net. 

PMID- 24321273
TI  - Sensory-guided motor tasks benefit from mental training based on serial
      prediction.
AB  - Mental strategies have been suggested to constitute a promising approach to
      improve motor abilities in both healthy subjects and patients. This behavioural
      effect has been shown to be associated with changes of neural activity in
      premotor areas, not only during movement execution, but also while performing
      motor imagery or action observation. However, how well such mental tasks are
      performed is often difficult to assess, especially in patients. We here used a
      novel mental training paradigm based on the serial prediction task (SPT) in order
      to activate premotor circuits in the absence of a motor task. We then tested
      whether this intervention improves motor-related performance such as sensorimotor
      transformation. Two groups of healthy young participants underwent a single
      blinded five-day cognitive training schedule and were tested in four different
      motor tests on the day before and after training. One group (N=22) received the
      SPT-training and the other one (N=21) received a control training based on a
      serial match-to-sample task. The results revealed significant improvements of the
      SPT-group in a sensorimotor timing task, i.e. synchronization of finger tapping
      to a visually presented rhythm, as well as improved visuomotor coordination in a
      sensory-guided pointing task compared to the group that received the control
      training. However, mental training did not show transfer effects on motor
      abilities in healthy subjects beyond the trained modalities as evident by non
      significant changes in the Jebsen-Taylor handfunctiontest. In summary, the data
      suggest that mental training based on the serial prediction task effectively
      engages sensorimotor circuits and thereby improves motor behaviour. 

PMID- 24321275
TI  - Reliability and validity of spinal coordination patterns during treadmill walking
      in persons with thoracic spine pain--a preliminary study.
AB  - BACKGROUND: Persons with low back pain fail to show the same transition as
      healthy individuals from in-phase to anti-phase rotation of the thorax and pelvis
      as walking speed increases. The purpose of this study was to determine if the
      relative phase of the thorax and pelvis during walking was a reliable (within day
      test-retest) and valid measure for persons with thoracic pain. METHODS: The time
      series motion of the spine over C7, T8 and sacrum were measured at five treadmill
      walking speeds (0.67, 0.89, 1.12, 1.34, 1.56 m/s) in 19 persons with thoracic
      spine pain and 19 healthy control subjects. After a 20 minute rest, all tests
      were repeated. The average relative phases of the transverse plane rotation
      between C7-T8, C7-sacrum and T8-sacrum during a one-minute walk were calculated.
      The standard error of measurement (SEM) and the intra-class correlation
      coefficient (ICC) were used to estimate test-retest reliability. Three-way
      repeated measures analyses of variance were performed to determine the influence
      of group, walking speed and session on the relative phases. RESULTS: The minimum
      transverse plane motion amplitudes, across all participants and speeds, for the
      C7-T8, C7-sacrum, and T8-sacrum were 2.9, 5.1 and 2.8 degrees, respectively. The
      C7-T8 relative phase changed little with speed. The C7-sacrum and T8-sacrum
      relative phases showed increases as subjects walked faster, but both groups had
      similar patterns of change. Only the C7-T8 relative phase at 0.67 and 0.89 m/s
      exhibited good reliability (ICC > 0.80, SEM 4.2-5.7, no significant time effects)
      for both groups. The C7-T8 and T8-sacrum relative phases demonstrated significant
      group by speed effects. CONCLUSIONS: The C7-T8 relative phase showed reasonable
      reliability and some discrimination between groups, but changes in response to
      walking speed were small. The T8-sacrum relative phase showed some discriminative
      ability, but reliability was not adequate.

PMID- 24321276
TI  - Immobilized cholinesterases capillary reactors on-flow screening of selective
      inhibitors.
AB  - The discovery of selective inhibitors for acetylcholinesterase (AChE) or
      butyrylcholinesterase (BChE) is extremely important for the development of drugs
      that can be used in the treatment of patients diagnosed with the Alzheimer's
      disease (AD). For this reason, there is a growing interest in developing rapid
      and effective assays techniques for cholinesterases (ChE) enzymes ligand
      screening. Herein is presented the results of selective screening assays of a
      coumarin derivatives library using BChE and AChE covalently immobilized onto
      silica fused capillaries (ICERs, 15 cm * 0.1 mm ID). The statistical comparison
      of the ICERs screening assay with that of the free enzymes is reported and
      highlights the advantages of the on-flow ICERs assay. Two out of 20 coumarin
      derivatives could be highlighted: compound 17 is more active toward BChE
      (IC50=109 +/- 21 MUM) and 19 showed activity against both enzymes (BChE IC50=128
      +/- 28 MUM and hu-AChE IC50=144 +/- 40 MUM). The statistical evaluation of the
      results of the ICERs and free enzyme assays showed no difference between them,
      further validating the ICERs assay model. The ICERs ability to recognize
      selective ligands and its use for characterization of the inhibition mechanisms
      of the hits consolidates the approach here reported.

PMID- 24321278
TI  - Regional differences in bronchial reactivity assessed by respiratory impedance.
AB  - We used the Impulse Oscillometric System (IOS) to gain information concerning the
      distribution of hyper-reactivity along the bronchial tree during methacholine
      challenge test (MCT). 37 subjects underwent MCT until reaching the provocative
      dose (PD20). At each dose, we estimated respiratory resistance at 5 and 20Hz (R5,
      R20), and reactance at 5Hz (X5). In non-responsive subjects (N=14) no changes in
      R5, R20, and X5 were observed during MCT. In responsive subjects, a wide spectrum
      of responses was found concerning frequency dependence and PD20. We describe two
      phenotypes representing the extremes of response. For PD20>400MUg (N=13), MCT
      caused equal changes of resistance/reactance on varying oscillation frequencies,
      suggesting a homogeneous bronchoconstriction along the bronchial tree. For
      PD20<200MUg (N=10), a remarkable frequency dependence was observed, with increase
      in R5, no change in R20, and decrease in X5, suggesting hyper-responsiveness of
      the distal airways paralleled by a change in visco-elastic properties of lung
      parenchyma. 

PMID- 24321279
TI  - Crystal structure of phosphoramide-phosphorylated thymidylate synthase reveals
      pSer127, reflecting probably pHis to pSer phosphotransfer.
AB  - Crystal structure is presented of the binary complex between potassium
      phosphoramidate-phosphorylated recombinant C. elegans thymidylate synthase and
      dUMP. On each monomer a single phosphoserine residue (Ser127) was identified,
      instead of expected phosphohistidine. As (31)P NMR studies of both the
      phosphorylated protein and of potassium phosphoramidate potential to
      phosphorylate different amino acids point to histidine as the only possible site
      of the modification, thermodynamically favored intermolecular phosphotransfer
      from histidine to serine is suggested. 

PMID- 24321280
TI  - Alternative ways of representing Zapotec and Cuicatec folk classification of
      birds: a multidimensional model and its implications for culturally-informed
      conservation in Oaxaca, Mexico.
AB  - BACKGROUND: We report on a comparative ethno-ornithological study of Zapotec and
      Cuicatec communities in Northern Oaxaca, Mexico that provided a challenge to some
      existing descriptions of folk classification. Our default model was the taxonomic
      system of ranks developed by Brent Berlin. METHODS: Fieldwork was conducted in
      the Zapotec village of San Miguel Tiltepec and in the Cuicatec village of San
      Juan Teponaxtla, using a combination of ethnographic interviews and pile-sorting
      tests. Post-fieldwork, Principal Component Analysis using NTSYSpc V. 2.11f was
      applied to obtain pattern variation for the answers from different participants.
      RESULTS AND CONCLUSION: Using language and pile-sorting data analysed through
      Principal Component Analysis, we show how both Zapotec and Cuicatec subjects
      place a particular emphasis on an intermediate level of classification.These
      categories group birds with non-birds using ecological and behavioral criteria,
      and violate a strict distinction between symbolic and mundane (or 'natural'), and
      between 'general-purpose' and 'single-purpose' schemes. We suggest that shared
      classificatory knowledge embodying everyday schemes for apprehending the world of
      birds might be better reflected in a multidimensional model that would also
      provide a more realistic basis for developing culturally-informed conservation
      strategies.

PMID- 24321277
TI  - Studies of metabolite-protein interactions: a review.
AB  - The study of metabolomics can provide valuable information about biochemical
      pathways and processes at the molecular level. There have been many reports that
      have examined the structure, identity and concentrations of metabolites in
      biological systems. However, the binding of metabolites with proteins is also of
      growing interest. This review examines past reports that have looked at the
      binding of various types of metabolites with proteins. An overview of the
      techniques that have been used to characterize and study metabolite-protein
      binding is first provided. This is followed by examples of studies that have
      investigated the binding of hormones, fatty acids, drugs or other xenobiotics,
      and their metabolites with transport proteins and receptors. These examples
      include reports that have considered the structure of the resulting solute
      protein complexes, the nature of the binding sites, the strength of these
      interactions, the variations in these interactions with solute structure, and the
      kinetics of these reactions. The possible effects of metabolic diseases on these
      processes, including the impact of alterations in the structure and function of
      proteins, are also considered. 

PMID- 24321281
TI  - Effect of BRCA1 on epidermal growth factor receptor in ovarian cancer.
AB  - BACKGROUND: Both BRCA1 and epidermal growth factor receptor (EGFR) play a
      critical role in ovarian cancer progression. However, the crosstalk between BRCA1
      and EGFR signaling pathways in ovarian cancer remains largely unknown. METHODS:
      The effect of BRCA1 on EGFR was assessed in 146 serous ovarian cancer patients
      (28 pairs of BRCA1-mutated or not, 23 pairs of BRCA2-mutated or not, and 22 pairs
      with hypermethylated BRCA1 promoter or not). BRCA1 promoter methylation was
      analyzed by bisulfite sequencing using primers flanking the core promoter region.
      Expression levels of BRCA1 and EGFR were assessed by immunohistochemistry and
      real-time PCR. The knockdown and overexpression of BRCA1 were achieved using a
      lentiviral vector in 293 T cells, SKOV3 ovarian cancer cells, and primary non
      mutated and BRCA1-mutated ovarian cancer cells. RESULTS: EGFR expression was
      increased in all cancer tissues compared to normal tissues. Additionally, EGFR
      expression was higher in normal tissues of BRCA1-mutated patients, and was
      further increased in cancer tissues; EGFR levels were also significantly elevated
      in ovarian cancer with promoter hypermethylation-mediated inactivation of BRCA1.
      BRCA1 knockdown was an effective way to activate EGFR expression in ovarian
      cancer cells. CONCLUSIONS: These results indicate that BRCA1 may be a potential
      trigger in transcriptional regulation of EGFR in the development of ovarian
      cancer.

PMID- 24321282
TI  - Dysfunction of alveolar macrophages after cardiac surgery and postoperative
      pneumonia?--An observational study.
AB  - INTRODUCTION: Patients undergoing cardiac surgery have an increased risk of
      postoperative pneumonia. Pulmonary immune dysfunction might be a contributing
      factor. We therefore determined changes of the surface molecules on alveolar
      macrophages (AMs). To characterize modulation in patients with pneumonia we
      correlated these changes to the development of postoperative pneumonia. METHODS:
      After ethical approval and written informed consent, 33 patients undergoing
      elective coronary bypass grafting surgery were included in this observational
      study. Peripheral blood cells and alveolar lavage fluid were collected directly
      after induction of anesthesia and two hours after separation from cardiopulmonary
      bypass (CPB). Human leukocyte antigen-DR (HLA-DR) and toll-like receptors (TLR)
      2/4 expression on monocytes and AM were assessed by flow cytometry. A total of
      three patients developed postoperative pneumonia determined according to the
      criteria of the Center of Disease Control. Statistical analysis was performed
      with the Mann-Whitney-U test and Wilcoxon test. RESULTS: We found significant
      changes of phenotypic and functional immune markers on AMs after cardiac surgery.
      HLA-DR expression on peripheral blood monocytes and AMs was significantly reduced
      compared to baseline in all patients (each approximately 30%). After surgery
      patients who developed postoperative pneumonia revealed a trend of stronger
      reduction of HLA-DR expression (83.7% versus 27.1%) and TLR4 expression on AMs
      (46.1% versus 9.9%) compared to patients without pneumonia. Already before
      surgery, the baseline of TLR2 expression on AM was significantly lower (27.7%) in
      patients who developed postoperative pneumonia. CONCLUSIONS: As far as we know
      this is the first study that shows an early impairment of lung cellular immune
      response after cardiac surgery. These findings can help to understand the role of
      cell-mediated immunosuppression and its association to the development of
      postoperative pneumonia.

PMID- 24321283
TI  - Algal sludge from Taihu Lake can be utilized to create novel PGPR-containing bio
      organic fertilizers.
AB  - Large amounts of refloated algal sludge from Taihu Lake result in secondary
      environmental pollution due to annual refloatation. This study investigated the
      possibility to produce bio-organic fertilizer (BIO) using algal sludge as a solid
      state fermentation (SSF) medium. Results showed that addition of algal sludge
      contributed to efficient SFF by a plant growth-promoting rhizobacteria (PGPR)
      strain SQR9 and improved the nutrient contents in the novel BIO. The optimum
      water content and initial inoculation size were 45% and 5%, respectively. After 6
      days of SSF, the biomass of strain SQR9 was increased to a cell density of more
      than 5 * 10(7) CFU g(-1). Microcystins were rapidly degraded, and a high
      germination index value was observed. Plant growth experiments showed that the
      produced BIO efficiently promoted plant growth. Additional testing showed that
      the novel SSF process was also suitable for other PGPR strains. This study
      provides a novel way of high-value utilization of algal sludge from Taihu Lake by
      producing low-cost but high-quality BIOs. 

PMID- 24321284
TI  - Treatment and decolorization of biologically treated Palm Oil Mill Effluent
      (POME) using banana peel as novel biosorbent.
AB  - Palm Oil Mill Effluent (POME) treatment has always been a topic of research in
      Malaysia. This effluent that is extremely rich in organic content needs to be
      properly treated to minimize environmental hazards before it is released into
      watercourses. The main aim of this work is to evaluate the potential of applying
      natural, chemically and thermally modified banana peel as sorbent for the
      treatment of biologically treated POME. Characteristics of these sorbents were
      analyzed with BET surface area and SEM. Batch adsorption studies were carried out
      to remove color, total suspended solids (TSS), chemical oxygen demand (COD),
      tannin and lignin, and biological oxygen demand (BOD) onto natural banana peel
      (NBP), methylated banana peel (MBP), and banana peel activated carbon (BPAC)
      respectively. The variables of pH, adsorbent dosage, and contact time were
      investigated in this study. Maximum percentage removal of color, TSS, COD, BOD,
      and tannin and lignin (95.96%, 100%, 100%, 97.41%, and 76.74% respectively) on
      BPAC were obtained at optimized pH of 2, contact time of 30 h and adsorbent
      dosage of 30 g/100 ml. The isotherm data were well described by the Redlich
      Peterson isotherm model with correlation coefficient of more than 0.99. Kinetic
      of adsorption was examined by Langergren pseudo first order, pseudo second order,
      and second order. The pseudo second order was identified to be the governing
      mechanism with high correlation coefficient of more than 0.99. 

PMID- 24321285
TI  - Enzyme activity as an indicator of soil-rehabilitation processes at a zinc and
      lead ore mining and processing area.
AB  - The activities of soil enzymes in relation to the changes occurring in the soil
      on a degraded area in southern Poland after zinc and lead mining were analyzed.
      An evaluation of the usefulness of urease and invertase activities for estimating
      the progress of the rehabilitation processes in degraded soil was performed. The
      data show that the soil samples differed significantly in organic carbon (0.68
      104.0 g kg(-1)) and total nitrogen (0.03-8.64 g kg(-1)) content in their surface
      horizons. All of the soil samples (apart from one covered with forest) had very
      high total concentrations of zinc (4050-10,884 mg kg(-1)), lead (959-6661 mg kg(
      1)) and cadmium (24.4-174.3 mg kg(-1)) in their surface horizons, and similar
      concentrations in their deeper horizons. Nevertheless, the amounts of the soluble
      forms of the above-mentioned heavy metals were quite low and they accounted for
      only a small percentage of the total concentrations: 1.4% for Zn, 0.01% for Pb
      and 2.6% for Cd. Urease activities were ranked as follows: soil from flotation
      settler (0.88-1.78 MUg N-NH4(+) 2h(-1) g(-1))<soil from old slag heaps (1.77-2.51
      MUg N-NH4(+) 2h(-1) g(-1))<soil undisturbed by mining activity (2.14-5.73 MUg N
      NH4(+) 2h(-1) g(-1)). Invertase activities were similar in soil that was
      undisturbed by mining and in soil from old slag heaps, ranging from 20.5 to
      77.1mg of the inverted sugar, but they were much lower in soil from the flotation
      settler (0.12-6.95 mg of the inverted sugar). The results demonstrated that heavy
      pollution with Zn, Pb and Cd slightly decreased the activities of urease and
      invertase. It is thought that it resulted from the enzyme reactions occurring in
      slightly acidic or alkaline soil conditions. Under such conditions, heavy metals
      occur mainly in insoluble forms. The activities of these enzymes are strongly
      dependent on the content and decomposition of organic matter in the soil.

PMID- 24321286
TI  - Criteria and indicators for the assessment of community forestry outcomes: a
      comparative analysis from Canada.
AB  - In Canada, there are few structured evaluations of community forestry despite
      more than twenty years of practice. This article presents a criteria and
      indicator framework, designed to elicit descriptive information about the types
      of socio-economic results being achieved by community forests in the Canadian
      context. The criteria and indicators framework draws on themes proposed by other
      researchers both in the field of community forestry and related areas. The
      framework is oriented around three concepts described as amongst the underlying
      objectives of community forestry, namely participatory governance, local economic
      benefits and multiple forest use. This article also presents the results of a
      field-based application of the criteria and indicators framework, comparing four
      case studies in three Canadian provinces. All four are community forests with
      direct tenure rights to manage and benefit from forestry activities. Results
      reveal that in terms of governance, the case studies adhere to two different
      models, which we name 'interest group' vs. 'local government'. Stronger
      participatory dimensions are evident in two case studies. In the area of local
      economic benefits, the four case studies perform similarly, with some of the
      strongest benefits being in employment creation, especially for those case
      studies that offer non-timber activities such as recreation and education. Two of
      four cases have clearly adopted a multiple-use approach to management. 

PMID- 24321287
TI  - Characterisation of the sintering behaviour of Waelz slag from electric arc
      furnace (EAF) dust recycling for use in the clay ceramics industry.
AB  - Waelz slag is an industrial by-product from the recovery of electric arc furnace
      (EAF) dust which is mainly sent to landfills. Despite the different chemical and
      mineralogical compositions of Waelz slag compared to traditional clays, previous
      experiments have demonstrated its potential use as a clay substitute in ceramic
      processes. Indeed, clayey products containing Waelz slag could improve mechanical
      and environmental performance, fixing most of the metallic species and moreover
      decreasing the release of some potential pollutants during firing. However, a
      deeper understanding of the complex phase transformations during its thermal
      treatment and the connection of this behaviour with the end properties is
      desirable in order to explain the role that is played by the Waelz slag and its
      potential contribution to the ceramic process. For this purpose, in the present
      study, the chemical, mineralogical, thermal and environmental behaviour of both
      (i) unfired powdered samples, and (ii) pressed specimen of Waelz slag fired up to
      different temperatures within the typical range of clay based ceramic production,
      has been studied. The effect of the heating temperature on the end properties of
      the fired samples has been assessed. In general, an increase of the firing
      temperature promotes sintering and densification of the products and decreases
      the open porosity and water absorption which also contributes to the fixation of
      heavy metals. On the contrary, an increase in the leaching of Pb, Cr and Mo from
      the fired specimens is observed. This can be attributed to the creation of Fe and
      Ca molybdates and chromates that are weakly retained in the alkali matrix. On the
      other side, at temperature above 950  degrees C a weight gain related to the
      emission of evolved gases is observed. In conclusion, the firing temperature of
      the ceramic process is a key parameter that affects not only the technical
      properties but also strongly affects the leaching behaviour and the process
      emissions. 

PMID- 24321288
TI  - Effect of residue combinations on plant uptake of nutrients and potentially toxic
      elements.
AB  - The aim of the plant pot experiment was to evaluate potential environmental
      impacts of combined industrial residues to be used as soil fertilisers by
      analysing i) element availability in fly ash and biosolids mixed with soil both
      individual and in combination, ii) changes in element phytoavailability in soil
      fertilised with these materials and iii) impact of the fertilisers on plant
      growth and element uptake. Plant pot experiments were carried out, using soil to
      which fresh residue mixtures had been added. The results showed that element
      availability did not correlate with plant growth in the fertilised soil with. The
      largest concentrations of K (3534 mg/l), Mg (184 mg/l), P (1.8 mg/l), S (760
      mg/l), Cu (0.39 mg/l) and Zn (0.58 mg/l) in soil pore water were found in the
      soil mixture with biosolids and MSWI fly ashes; however plants did not grow at
      all in mixtures containing the latter, most likely due to the high concentration
      of chlorides (82 g/kg in the leachate) in this ash. It is known that high
      salinity of soil can reduce germination by e.g. limiting water absorption by the
      seeds. The concentrations of As, Cd and Pb in grown plants were negligible in
      most of the soils and were below the instrument detection limit values. The
      proportions of biofuel fly ash and biosolids can be adjusted in order to balance
      the amount and availability of macronutrients, while the possible increase of
      potentially toxic elements in biomass is negligible seeing as the plant uptake of
      such elements was low. 

PMID- 24321289
TI  - Outcomes of tympanostomy tube placement in children with Down syndrome--a
      retrospective review.
AB  - OBJECTIVES: Tympanostomy tubes are commonly used for treatment of chronic otitis
      media with effusion (COME) or recurrent acute otitis media (RAOM) in patients
      with Down syndrome, but hearing outcomes in this population have been mixed, and
      complications appear to be common. We aim to characterize outcomes and
      complications associated with tympanostomy tube placement in this population.
      METHODS: Retrospective review. All patients with Down syndrome presenting to a
      tertiary academic pediatric otolaryngology practice over a ten year period from
      2002 to 2012 who received tympanostomy tubes for COME, RAOM, or hearing loss were
      reviewed. RESULTS: Long term follow up data was obtained in 102 patients, with
      average follow up 4.7 years. COME was the primary indication for tube placement
      in 100/102 (98%). Less than half of these patients (44%) initially failed their
      newborn hearing screen. Post operative hearing was found to be normal or near
      normal for the better hearing ear in 85/99 (85.9%), and normal to near normal in
      bilateral ears in 71/99 (71%). A majority (63.7%) of patients required two or
      more sets of tubes during the follow up period. Long term complications were
      common and were significantly increased if the patient required three or more
      sets of tubes, including chronic perforation (36.6% vs 8.2%, p<0.001),
      atelectasis (29.3% vs 1.6%, p<0.0001), and cholesteatoma (14.6% vs 0%, p=0.003).
      CONCLUSIONS: COME is a frequent problem in Down syndrome, and the majority of
      patients will require two or more sets of tubes during their childhood and
      achieve normal postoperative hearing. Long term complications of otitis media
      appear to be more common in this population and appear to correlate with
      increasing number of tubes placed. More investigation is required to determine
      optimal treatment strategies for COME in patients with Down syndrome.

PMID- 24321290
TI  - Time of injury affects urinary biomarker predictive values for acute kidney
      injury in critically ill, non-septic patients.
AB  - BACKGROUND: The predictive value of acute kidney injury (AKI) urinary biomarkers
      may depend on the time interval following tubular injury, thereby explaining in
      part the heterogeneous performance of these markers that has been reported in the
      literature. We studied the influence of timing on the predictive values of
      tubular proteins, measured before the rise of serum creatinine (SCr) in
      critically ill, non-septic patients. METHODS: Seven hundred adult critically ill
      patients were prospectively included for urine measurements at four time-points
      prior to the rise in serum creatinine (T = 0, -16, -20 and -24 h). Patients with
      sepsis and or AKI at ICU entry were excluded. The urinary excretion of the
      proteins, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury
      molecule-1 (KIM-1), which are up-regulated in the distal and proximal tubules,
      respectively, were measured as well as the constitutive cytoplasmatic enzymes, pi
      and alpha-glutathione-S-transferase (GST), which are released by the distal and
      proximal tubules, respectively. RESULTS: Five hundred and forty-three subjects
      were eligible for further analyses; however, 49 developed AKI in the first 48 h.
      Both NGAL (P = 0.001 at T = -24 vs. non-AKI patients) and KIM-1 (P < 0.0001 at T
      = 0 vs. non-AKI patients) concentrations gradually increased until AKI diagnosis,
      whereas pi- and alpha-GST peaked at T = -24 before AKI (P = 0.006 and P = 0.002,
      respectively vs. non-AKI patients) and showed a rapid decline afterwards. The
      predictive values at T = -24 prior to AKI were modest for pi- and alpha-GST,
      whereas NGAL sufficiently predicted AKI at T = -24 and its predictive power
      improved as the time interval to AKI presentation decreased (area under the
      receiver operating characteristic curve; AUC = 0.79, P < 0.0001). KIM-1 was a
      good discriminator at T = 0 only (AUC = 0.73, P < 0.0001). CONCLUSIONS: NGAL, KIM
      1, pi- and alpha-GST displayed unique and mutually incomparable time dependent
      characteristics during the development of non-sepsis related AKI. Therefore, the
      time-relationship between the biomarker measurements and the injurious event
      influences the individual test results.

PMID- 24321291
TI  - Neurochemical study of amino acids in rodent brain structures using an improved
      gas chromatography-mass spectrometry method.
AB  - The analysis of amino acid levels is crucial for neuroscience studies because of
      the roles of these molecules as neurotransmitters and their influence on
      behavior. The present study describes the distribution and levels of 16 amino
      acids (alanine, asparagine, aspartic acid, cysteine, glycine, glutamic acid,
      isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine,
      serine, valine, and threonine) in brain tissues (prefrontal cortex, striatum,
      hippocampus and cerebellum) and the serum. Neurochemical analysis was performed
      on Wistar rats and C57BL/6 mice using an efficient method for extraction, a fast
      microwave-assisted derivatization and gas chromatography-mass spectrometry
      analysis. The amino acid concentration varied across brain regions for 14 of the
      16 analyzed molecules, with detection limits ranging from 0.02+/-0.005MUmolL(-1)
      to 7.07+/-0.05MUmolL(-1). In rats, the concentrations of alanine, glycine,
      methionine, serine and threonine were higher in prefrontal cortex than in other
      areas, whereas in mice, the concentrations of glutamic acid, leucine and proline
      were highest in the hippocampus. In conclusion, this study provides a cerebral
      profile of amino acids in brain regions and the serum of rats and mice. 

PMID- 24321292
TI  - Lipid fermentation of corncob residues hydrolysate by oleaginous yeast
      Trichosporon cutaneum.
AB  - Corncob residues (CCR) are cellulose residues of corncob after xylan
      (hemicellulose) is extracted for production of xylitol. Here, an oleaginous yeast
      Trichosporon cutaneum ACCC 20271 was screened for lipid fermentation using CCR
      hydrolysate. The initial carbon-to-nitrogen molar ratio (C/N ratio) and the
      initial sugar concentration of the CCR hydrolysate were investigated in the lipid
      fermentation of T. cutaneum ACCC 20271. A C/N ratio gradient was generated by
      changing the corn steep liquor (CSL) addition and an optimal C/N ratio of 49.3
      was obtained. The different initial sugar concentration was obtained by changing
      the cellulase amount and the lipid titer was enhanced by the increased sugar
      concentration. To our knowledge, this is the first report on using CCR as the
      feedstock for lipid fermentation. The lipid titer of 12.3g/L and dry cell weight
      (DCW) of 38.4 g/L were the highest values among the studies using lignocellulose
      for lipid production.

PMID- 24321293
TI  - Effect of smear layer deproteinizing on resin-dentine interface with self-etch
      adhesive.
AB  - OBJECTIVES: This study aimed to investigate deproteinizing effect of sodium
      hypochlorite (NaOCl) and mild acidic hypochlorous-acid (HOCl) pretreatment on
      smear layer-covered dentine and to evaluate their effects on morphological
      characteristics of resin-dentine interface with self-etch adhesive. METHODS:
      Human coronal-dentine discs with standardized smear layer were pretreated with 6%
      NaOCl or 50ppm HOCl for 15s or 30s. Their deproteinizing effects at the treated
      smear layer-covered dentine surfaces were determined by the measurement of
      amide:phosphate ratio using ATR-FTIR analysis. In addition, using TEM,
      micromorphological alterations of hybridized complex and nanoleakage expression
      were evaluated at the interface of a self-etch adhesive (Clearfil SE Bond) to the
      pretreated dentine surface with or without subsequent application of a reducing
      agent (p-Toluenesulfinic acid salt; Accel((r))). RESULTS: Both pretreatments of
      NaOCl and HOCl significantly reduced the amide:phosphate ratio as compared with
      the no-pretreated group (p<0.05), coincident with the elimination of the
      hybridized smear layer on their bonded interfaces. Nanoleakage within the hybrid
      layer was found in the no-pretreated and NaOCl-pretreated groups, whereas the
      subsequent reducing agent application changed the reticular nanoleakage to
      spotted type. HOCl-pretreated groups showed less nanoleakage expression in a
      spotted pattern, regardless of reducing agent application. CONCLUSIONS: NaOCl and
      HOCl solutions could remove the organic component on the smear layer-covered
      dentine, which could eliminate the hybridized smear layer created by self-etch
      adhesive, leading to the reduction of nanoleakage expression within hybrid layer.
      CLINICAL SIGNIFICANCE: Smear layer deproteinizing could modify dentine surface,
      giving an appropriate substrate for bonding to self-etch adhesive system.

PMID- 24321294
TI  - Diagnostic accuracy of CBCT for tooth fractures: a meta-analysis.
AB  - OBJECTIVES: The objective of this meta-analysis was to determine the diagnostic
      accuracy of cone-beam computed tomography (CBCT) for tooth fractures in vivo.
      METHODS: PubMed, Embase, Web of Science, ProQuest Dissertations & Theses, CNKI
      and SIGLE were searched from January 1990 to April 2013 for eligible studies.
      Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was employed to
      assess the quality of the included studies. Meta-analyses were performed in
      MetaDisc 1.4, Stata 12.1 and StatsDirect 2.7.9. RESULTS: Finally, 12 studies were
      included in this meta-analysis. The pooled sensitivity, specificity, positive
      likelihood ratio, negative likelihood ratio and summary receiver operating
      characteristic were 0.92 (95% CI=0.89-0.94), 0.85 (95% CI=0.75-0.92), 5.68 (95%
      CI=3.42-9.45), 0.13 (95% CI=0.09-0.18) and 0.94 (95% CI=0.90-0.98), respectively.
      The pooled prevalence of tooth fractures in patients with clinically-suspected
      but periapical-radiography-undetected tooth fractures was 91% (95% CI=83%-97%).
      Positive and negative predictive values were 0.98 and 0.43 (subgroup analysis:
      0.98 and 0.28 for endodontically-treated teeth; 0.99 and 0.77 for non
      endodontically-treated teeth). CONCLUSION: We suggest that CBCT has a high
      diagnostic accuracy for tooth fractures and could be used in clinical settings.
      We can be very confident with positive test results but should be very cautious
      with negative test results, especially for endodontically treated teeth.

PMID- 24321295
TI  - Numerical study of the influence of material parameters on the mechanical
      behaviour of a rehabilitated edentulous mandible.
AB  - OBJECTIVES: The study dealt with full dental prosthetic reconstruction on four
      implants. The aim was to analyse the influence of material parameters on the
      mechanical behaviour of the restored mandible compared to the natural mandible.
      METHODS: A finite element model of an edentulous mandible with prosthetic
      rehabilitation was established. Four materials were investigated for the
      framework of the prosthesis (zirconia, titanium, gold and nickel-titanium
      (NiTi)), as well as three cortical bone thicknesses. Various muscles were
      employed to simulate the main stages of mastication. Three distinct phases of
      mastication were modelled: maximum intercuspation, incisal clench and unilateral
      molar clench. RESULTS: The zirconia framework demonstrated the highest stresses
      and NiTi the weakest. The highest stresses in the framework were obtained during
      maximum intercuspation. The highest stresses at the bone-implant interface were
      recorded on the working axial implant during unilateral molar clench and on
      tilted implants during maximum intercuspation. The influence of the framework's
      material stiffness on the stresses at the bone-implant interface was
      insignificant for axial implants (except the right implant during unilateral
      molar clench) and slightly more significant for tilted implants. Mandibular
      flexion decreased with an increase of the cortical bone thickness and the
      stiffness of the prosthetic framework's material. CONCLUSIONS: Among all
      materials, NiTi allowed a better preservation of the mandibular flexure, during
      all the mastication stages. Compared to stiffer materials, NiTi also permitted
      physiological mechanical conditions at the bone/implant interface, in almost all
      mastication stages.

PMID- 24321297
TI  - Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer
      cells.
AB  - BACKGROUND: Regulation of mRNAs is one way to control protein levels and thereby
      important cellular processes such as growth, invasion and apoptosis. G3BPs
      constitute a family of mRNA-binding proteins, shown to be overexpressed in
      several cancer types, including breast, colon and pancreas cancer. G3BP has been
      reported to both stabilize and induce degradation of specific mRNAs. RESULTS:
      Here, we show that G3BP1, but not G3BP2, supports proliferation of several breast
      cancer cell lines. Global gene expression analyses of G3BP1- and G3BP2-depleted
      cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA
      expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was
      significantly influenced by G3BP1 depletion which led to a 2-3 fold increased
      expression. Depletion of PMP22 resulted in increased proliferation and the G3BP1
      mediated effect on proliferation was not seen upon PMP22-depletion. CONCLUSIONS:
      This indicates a novel role for G3BP1 in the regulation of cell proliferation in
      breast cancer cells, perhaps via a regulatory effect on PMP22 expression.

PMID- 24321298
TI  - An exploration in acoustic radiation force experienced by cylindrical shells via
      resonance scattering theory.
AB  - In nonlinear acoustic regime, a body insonified by a sound field is known to
      experience a steady force that is called the acoustic radiation force (RF). This
      force is a second-order quantity of the velocity potential function of the
      ambient medium. Exploiting the sufficiency of linear solution representation of
      potential function in RF formulation, and following the classical resonance
      scattering theorem (RST) which suggests the scattered field as a superposition of
      the resonant field and a background (non-resonant) component, we will show that
      the radiation force is a composition of three components: background part,
      resonant part and their interaction. Due to the nonlinearity effects, each part
      contains the contribution of pure partial waves in addition to their mutual
      interaction. The numerical results propose the residue component (i.e.,
      subtraction of the background component from the RF) as a good indicator of the
      contribution of circumferential surface waves in RF. Defining the modal series of
      radiation force function and its components, it will be shown that within each
      partial wave, the resonance contribution can be synthesized as the Breit-Wigner
      form for adequately none-close resonant frequencies. The proposed formulation may
      be helpful essentially due to its inherent value as a canonical subject in
      physical acoustics. Furthermore, it may make a tunnel through the circumferential
      resonance reducing effects on radiation forces. 

PMID- 24321296
TI  - The effects of ageing on the biomechanical properties of root dentine and
      fracture.
AB  - OBJECTIVES: Knowledge of the mechanical behaviour of root dentine can facilitate
      better understanding of spontaneous vertical root fracture (VRF), an age-related
      disease initiated mainly at the root apex. We tested the hypothesis that the
      biomechanical properties of root dentine change with ageing. METHODS: Sixteen
      human premolars were divided into "old" (17-30 years) and "young" (50-80 years)
      groups. The elastic modulus, nano-hardness, micro-hardness, elemental contents,
      tubular density/area of root dentine in cervical, middle and apical root regions
      were evaluated using atomic force microscopy-based nano-indentation, Knoop
      indentation, scanning electron microscopy and energy dispersive X-ray
      spectroscopy, respectively. RESULTS: The apical dentine showed a lower nano
      hardness, a lower elastic modulus, a lower calcium content, a lower calcium-to
      phosphorus ratio and a smaller tubular density/area than the cervical dentine in
      both age groups, whereas spatial differences in micro-hardness were observed only
      in old roots. Compared with young dentine, old dentine showed a greater hardness,
      a higher elastic modulus, a greater mineral content and a smaller tubular size in
      the cervical portion, whereas the age-induced changes in tubular density were
      insignificant. Finite element analysis revealed that due to its higher elastic
      modulus, old apical dentine has a higher stress level than young dentine.
      CONCLUSIONS: The intrinsic material properties of root dentine have spatial
      variations, and they are altered by ageing. The higher stress level in old apical
      dentine may be one reason, if not the most important one, why spontaneous VRFs
      are more likely to occur in the elderly population.

PMID- 24321299
TI  - The effects of Ce6-mediated sono-photodynamic therapy on cell migration,
      apoptosis and autophagy in mouse mammary 4T1 cell line.
AB  - PURPOSE: Sono-Photodynamic therapy (SPDT) is an alternative therapy which claims
      to enhance the anti-cancer effects by combining sonodynamic therapy (SDT) with
      photodynamic therapy (PDT). In the present study, we investigated the effects of
      chlorin e6 (Ce6) mediated SPDT on migration, apoptosis and autophagy in mouse
      mammary 4T1 cancer cells, and its underlying mechanisms. MATERIALS: Cell
      migration was determined by wound healing assay. Apoptosis was analyzed using
      annexin V-PE/7-ADD staining as well as Hoechst 33342 staining. Changes of
      mitochondria membrane potential (MMP) was evaluated by flow cytometry. Formation
      of acidic vesicular organelles (AVOs) during autophagy was observed with
      fluorescence microscope by MDC staining. Immunofluorescence assays were performed
      to detect the co-localization of LC3 and Lamp2. Western blotting was employed to
      analyze the activity of the apoptosis related proteins Caspase-3, PARP, Bax and
      Bcl-2, as well as the autophagy associated processing of LC3-I to LC3-II and
      Beclin-1 expression. RESULTS: Ce6 mediated SPDT further enhanced cell migration
      inhibition, significantly triggered cell apoptosis, nuclear condensation and MMP
      drop. Cleaved Caspase-3 and PARP increased dramatically after Ce6-SPDT,
      accompanied by decreased Bcl-2 expression, while the expression of Bax remained
      stable. Additionally, AVOs formation, co-localization of LC3 and Lamp2 occurred
      following Ce6-SPDT and simultaneously accompanied by LC3-II processing and
      increased Beclin-1 expression. CONCLUSIONS: Ce6-SPDT could enhance cell migration
      inhibition, and induce mitochondria-dependent apoptosis as well as autophagy in
      4T1 cells.

PMID- 24321300
TI  - The controversy of peri-operative beta-blockade: what should I do?

PMID- 24321301
TI  - Prostate cancer in deceased organ donors: a review.
AB  - OBJECTIVE: To estimate the risk of prostate cancer transmission in relation with
      organ procurement. METHODS: A literature search from the Medline database using
      the following keywords-transplantation, prostate cancer, organ procurement, donor
      transmitted malignancies, disease transmission, staging, evaluation, and PSA-was
      conducted to select 16 articles written in English and French over the last 15
      years. RESULTS: The incidence of prostate cancer in deceased organ donors (DOD)
      has been estimated to be between 3% and 18.5%. There were more than 120 solid
      organ transplantations performed with organs coming from DOD with a proven
      prostate cancer without any case of cancer transmission or death related to
      malignancy and only 1 case of transmission by the donor after a heart transplant
      has been described. CONCLUSION: Transmission of prostate cancer by a transplanted
      organ seems incidental. When PSA is measured, it should be suspected only if the
      value is beyond 20 ng/ml and in all cases, should be interpreted taking digital
      rectal examination (DRE) into account. Organs from a DOD with a DRE proving a T3
      T4 prostate cancer should not be procured. Suspect iliac lymph nodes during the
      preparation of the vessels for cannulation must lead to the discontinuation of
      the procurement or a histological analysis.

PMID- 24321302
TI  - Urine proteomics in kidney transplantation.
AB  - The transplanted kidney, through its urinary output, provides a medium through
      which the molecular constitution can provide insight into either the healthy
      function or developing dysfunction of a newly transplanted organ. An assay that
      would detect the aberration of early biomarkers of allograft injury using only
      urine samples from patients would provide many advantages over the current use of
      creatinine and tissue biopsies, as these means are either relatively non-specific
      or very invasive. Several urine biomarkers have been correlated with allograft
      injury, including CXCL9, CXCL10, CCL2, NGAL, IL-18, cystatin C, KIM-1 and Tim-3.
      The recent results of the CTOT-01 trial serve to validate the predictive value of
      the CXCL9 biomarker as a non-invasive biomarker for rejection and a prognostic
      indicator of graft function. There is now a preponderance of evidence showing a
      value of urinary monitoring of CXCL9 and CXCL10 with respect to detection of
      acute kidney allograft rejection. The value of the assay has been validated as a
      means of reducing the need for kidney transplant biopsy and applying biopsy in a
      more targeted manner. Additional goals for non-invasive monitoring would include
      predictive value prior to creatinine elevation that in turn would permit earlier,
      preemptive treatment of rejection. 

PMID- 24321303
TI  - Innate immunity in renal transplantation: the role of mannose-binding lectin.
AB  - Innate immune system plays an important role in the modulation of the
      inflammatory response during infection and tissue injury/repair. Mannose-binding
      lectin (MBL) is a component of the innate immune system that activates complement
      via the lectin pathway. Different polymorphisms of the MBL gene are associated
      with MBL levels and MBL function. The relationship between MBL and disease is
      rather complex because MBL behaves as a double-edged sword. In the general
      population, low serum MBL levels are associated with higher risk of infection,
      type 2 diabetes, autoimmune and cardiovascular disease. However, in patients with
      diabetes or autoimmune disease, high MBL levels are associated with more severe
      renal and cardiovascular comorbidities. In renal transplantation, low MBL serum
      levels constitute a risk factor for infection, low grade inflammation, new onset
      diabetes after transplantation and subclinical rejection. Despite these
      associations suggest that low MBL levels should be associated with poorer renal
      allograft outcome, epidemiological studies evaluating the predictive value of MBL
      levels on graft survival are controversial. Taken together, these observations
      suggest that low MBL serum levels modulate chronic inflammatory response that may
      influence transplant outcome. 

PMID- 24321304
TI  - The role of mycophenolate mofetil in kidney transplantation revisited.
AB  - Since its regulatory approval in 1995, mycophenolate mofetil (MMF) has largely
      replaced azathioprine (AZA) as the anti-metabolite immunosuppressive of choice in
      kidney transplantation. While the initial industry-sponsored clinical trials
      suggested strong reductions in the incidence of acute rejection in the first six
      months post transplantation, long-term follow-up studies have failed to
      demonstrate a similar degree of benefit in overall graft and patient survival. In
      addition, several subsequent studies have raised questions on the potential
      attenuating effects of calcineurin inhibitor choice on MMF efficacy when compared
      to AZA. This review will revisit the question of whether the available evidence
      continues to support the superiority of MMF over AZA in kidney transplantation
      outcomes while comprehensively reviewing the available evidence from clinical
      trial data, systematic reviews, and registry studies. 

PMID- 24321305
TI  - Visceral leishmaniasis after kidney transplantation: report of a new case and a
      review of the literature.
AB  - Visceral leishmaniasis (VL) is a parasitic disease, caused by protozoa of the
      genus Leishmania, transmitted by the phlebotomies sand fly. In the last 20 years,
      the increasing frequency of organ transplantations and the improvement of
      associated immunosuppressive treatments have led to the recognition of several
      cases of VL complicating organ transplantation. Actually, less than 100 cases of
      VL after kidney transplantation are reported in the literature. In this context,
      VL is fatal without antileishmanial treatment which constitutes a difficult
      challenge. We report a case of VL in Tunisian renal transplant recipient treated
      successfully by liposomal amphotericin B (Ambisome(r), Gilead Sciences Inc).
      Also, we review the epidemiological, clinical, biological and therapeutic aspects
      of VL associated with renal transplantation reported in the literature. Our
      report identifies that VL should be suspected in renal transplant recipients
      presenting unexplained fever, splenomegaly and pancytopeny. It also suggests a
      serological testing for leishmaniasis in the pre-operative check-up of transplant
      patients and donors living or traveling in endemic areas of leishmaniasis.
      Moreover, recipients should be tested regularly for leishmaniasis after
      transplantation. Liposomal amphotericin B may be considered the treatment of
      choice of VL, since it has a lower incidence of side effects.

PMID- 24321306
TI  - A kernel machine-based fMRI physiological noise removal method.
AB  - Functional magnetic resonance imaging (fMRI) technique with blood oxygenation
      level dependent (BOLD) contrast is a powerful tool for noninvasive mapping of
      brain function under task and resting states. The removal of cardiac- and
      respiration-induced physiological noise in fMRI data has been a significant
      challenge as fMRI studies seek to achieve higher spatial resolutions and
      characterize more subtle neuronal changes. The low temporal sampling rate of most
      multi-slice fMRI experiments often causes aliasing of physiological noise into
      the frequency range of BOLD activation signal. In addition, changes of heartbeat
      and respiration patterns also generate physiological fluctuations that have
      similar frequencies with BOLD activation. Most existing physiological noise
      removal methods either place restrictive limitations on image acquisition or
      utilize filtering or regression based post-processing algorithms, which cannot
      distinguish the frequency-overlapping BOLD activation and the physiological
      noise. In this work, we address the challenge of physiological noise removal via
      the kernel machine technique, where a nonlinear kernel machine technique, kernel
      principal component analysis, is used with a specifically identified kernel
      function to differentiate BOLD signal from the physiological noise of the
      frequency. The proposed method was evaluated in human fMRI data acquired from
      multiple task-related and resting state fMRI experiments. A comparison study was
      also performed with an existing adaptive filtering method. The results indicate
      that the proposed method can effectively identify and reduce the physiological
      noise in fMRI data. The comparison study shows that the proposed method can
      provide comparable or better noise removal performance than the adaptive
      filtering approach. 

PMID- 24321307
TI  - Maximum likelihood estimation for second level fMRI data analysis with
      expectation trust region algorithm.
AB  - The trust region method which originated from the Levenberg-Marquardt (LM)
      algorithm for mixed effect model estimation are considered in the context of
      second level functional magnetic resonance imaging (fMRI) data analysis. We first
      present the mathematical and optimization details of the method for the mixed
      effect model analysis, then we compare the proposed methods with the conventional
      expectation-maximization (EM) algorithm based on a series of datasets (synthetic
      and real human fMRI datasets). From simulation studies, we found a higher damping
      factor for the LM algorithm is better than lower damping factor for the fMRI data
      analysis. More importantly, in most cases, the expectation trust region algorithm
      is superior to the EM algorithm in terms of accuracy if the random effect
      variance is large. We also compare these algorithms on real human datasets which
      comprise repeated measures of fMRI in phased-encoded and random block experiment
      designs. We observed that the proposed method is faster in computation and robust
      to Gaussian noise for the fMRI analysis. The advantages and limitations of the
      suggested methods are discussed. 

PMID- 24321308
TI  - Within a sample from a population, the distribution of the number of descendants
      of a subsample's most recent common ancestor.
AB  - Sample n individuals uniformly at random from a population, and then sample m
      individuals uniformly at random from the sample. Consider the most recent common
      ancestor (MRCA) of the subsample of m individuals. Let the subsample MRCA have j
      descendants in the sample (m ? j ? n). Under a Moran or coalescent model (and
      therefore under many other models), the probability that j = n is known. In this
      case, the subsample MRCA is an ancestor of every sampled individual, and the
      subsample and sample MRCAs are identical. The probability that j = m is also
      known. In this case, the subsample MRCA is an ancestor of no sampled individual
      outside the subsample. This article derives the complete distribution of j,
      enabling inferences from the corresponding p-value. The text presents
      hypothetical statistical applications pertinent to taxonomy (the gene flow
      between Neanderthals and anatomically modern humans) and medicine (the
      association of genetic markers with disease).

PMID- 24321309
TI  - Sequential bilateral testicular tumours presenting with intervals of 20 years and
      more.
AB  - BACKGROUND: About 3-5% of all patients with testicular germ cell tumour (GCT)
      develop a contralateral cancer, the majority of which arise within 10-15 years.
      Little is known about the risk of second GCTs after more than two decades. Here
      we present 3 cases with very late presenting contralateral GCT and provide a
      summary of similar cases reported previously. CASE PRESENTATIONS: (1) This white
      Caucasian man underwent right-sided orchiectomy for a nonseminomatous GCT at the
      age of 22 years. Additional treatment consisted of retroperitoneal lymph node
      dissection (RPLND) and chemotherapy with 4 cycles of vinblastin / bleomycin. 36
      years later, contralateral seminoma clinical stage 1 developed. Cure was achieved
      by orchiectomy. Histologically, testicular intraepithelial neoplasia (TIN;
      intratubular germ cell neoplasia) was detected in the tumour-surrounding
      tissue.(2) This white Caucasian male had right-sided orchiectomy for
      nonseminomatous GCT at the age of 29 years. Pathological stage 1 was confirmed by
      RPLND. 25 years later, he received left sided orchiectomy for seminoma stage 1.
      Histologically, TIN was found in the tissue adjacent to seminoma. Two brothers
      had testicular GCT, too, one with bilateral GCT. (3) This 21 year old white
      Caucasian man underwent left-sided orchiectomy for nonseminomatous GCT.
      Pathological stage 1 was confirmed by RPLND. 21 years later, he received organ
      preserving excision of a right-sided seminoma, followed by BEP chemotherapy for
      stage 3 disease. Histologically, TIN was found in the surrounding testicular
      tissue.22 cases of bilateral GCT with intervals of 20 or more years have
      previously been reported, thereof three with intervals of more than 30 years, the
      longest interval being 40 years. CONCLUSION: Apart from increased risks of
      cardiovascular diseases and non-testicular malignancies, patients with GCT face
      the specific probability of a second GCT in the long run. This risk persists life
      long and is not eliminated by chemotherapy. Contralateral testicular biopsy can
      identify patients at risk by revealing precursor cells of GCT though false
      negative biopsies may occur sporadically. However, in view of the multi-facetted
      late hazards of GCT patients, this minor surgical procedure might somewhat
      simplify the long-time care of these patients.

PMID- 24321310
TI  - Total spontaneous regression of a central giant cell granuloma after incisional
      biopsy: a four-year follow-up case report.
AB  - Central giant cell granuloma (CGCG) of the jaws represents a localized and benign
      neoplastic lesion sometimes characterized by aggressive osteolytic proliferation.
      The World Health Organization defines it as an intraosseous lesion composed of
      cellular and dense connective tissues that contain multiple hemorrhagic foci, an
      aggregation of multinucleated giant cells, and occasional bone tissue trabeculae.
      The origin of this lesion is uncertain; however, factors such as local trauma,
      inflammation, intraosseous hemorrhage, and genetic abnormalities have been
      identified as possible causes. CGCG generally affects those younger than 30 years
      and occurs more frequently in women (2:1). This lesion corresponds to
      approximately 7% of all benign tumors of the jaws, with prevalence in the
      anterior region of the jaw. Aggressive lesions are characterized by symptoms,
      such as pain, numbness, rapid growth, cortical perforation, root resorption, and
      a high recurrence rate after curettage. In contrast, nonaggressive CGCGs have a
      slow rate of growth, may contain sparse trabeculation, and are less likely to
      move teeth or cause root resorption or cortical perforation. Nonaggressive CGCGs
      are generally asymptomatic lesions and thus are frequently found on routine
      dental radiographs. Radiographically, the 2 forms of CGCG present as radiolucent,
      expansive, unilocular or multilocular masses with well-defined margins. The
      histopathology of CGCG is characterized by multinucleated giant cells, surrounded
      by round, oval, and spindle-shaped mononuclear cells, scattered in dense
      connective tissue with hemorrhagic and abundant vascularization foci. The final
      diagnosis is determined by histopathologic analysis of the biopsy specimen. The
      preferred treatment for CGCG consists of excisional biopsy, curettage with a
      safety margin, and partial or total resection of the affected bone. Conservative
      treatments include local injections of steroids, calcitonin, and antiangiogenic
      therapy. Drug treatment using antibiotics, painkillers, and corticosteroids and
      clinical and radiographic monitoring are necessary for approximately 10 days
      after surgery. There are only a few cases of spontaneous CGCG regression
      described in the literature; therefore, a detailed case report of CGCG regression
      in a 12-year-old boy with a 4-year follow-up is presented and compared with
      previous studies. 

PMID- 24321311
TI  - Composite three-layer closure of oral antral communication with 10 months follow
      up-a case study.
AB  - PURPOSE: We propose a 3-layer composite closure technique for an oral antral
      communication (OAC) while avoiding secondary donor site morbidity. PATIENTS AND
      METHODS: A patient had developed a 1-cm OAC after extraction of right maxillary
      first molar. The patient subsequently developed acute maxillary sinusitis. The
      patient was taken to the operating room, and a Caldwell-Luc procedure was
      performed. The bony window from the Caldwell-Luc was "press fit" over the bony
      OAC defect. Soft tissue closure was then achieved with a buccal fat pad flap and
      a buccal mucosal advancement flap. The patient was examined on postoperative day
      5 and 1, 2, 3, 6, and 10 months postoperatively. RESULTS: The acute sinusitis had
      resolved. The soft tissue closure was successful. The bone graft remained intact,
      prevented sinus pneumatization, and restored continuity to the floor of the
      maxillary sinus. CONCLUSIONS: The presented technique for 3-layer closure of OACs
      allows for the stability of a double-layer closure of OAC with the added benefit
      of bone grafting from single operative site, achieving stable oral antral
      closure, bone grafting, and the avoidance of secondary donor site morbidity.

PMID- 24321312
TI  - Alveolar sandwich osteotomy in resorbed alveolar ridge for dental implants: a 4
      year prospective study.
AB  - PURPOSE: To answer whether severe vertical alveolar defects can be resolved using
      the sandwich osteotomy technique with xenograft material as filler and to
      evaluate the predictability of this procedure. MATERIALS AND METHODS: Ten graft
      sites (5 mandibular and 5 maxillary) in 9 patients treated at the Department of
      Oral and Maxillofacial Surgery, Hadassah Medical Center, were included in the
      present study. The patients underwent vertical bone augmentation using the
      sandwich osteotomy technique filled with xenograft material. The degree of bone
      augmentation was analyzed clinically at surgery and 4 to 6 months later from the
      computed tomography images taken just before the sites had been rehabilitated
      using dental implant insertion. A trephine histologic analysis was performed
      during implantation at 1 maxillary site. RESULTS: The mean vertical bone gain in
      the interval between the sandwich osteotomy and implementation was 6 mm (range 4
      to 10), and it remained stable after 4 to 6 months. In 2 cases, additional
      horizontal bone augmentation was needed. All graft sites were rehabilitated using
      dental implants with satisfactory results. In 3 cases, gingival porcelain was
      required for the final prosthesis. Histologic examination revealed vital
      segmentized bone and remodeling of the filled gap. CONCLUSIONS: The
      interpositional alveolar bone graft using xenograft filler appears to be a viable
      and predictable alternative to block grafting or guided bone regeneration,
      resulting in good final results, with substantial vertical bone gain, even for
      challenging cases.

PMID- 24321313
TI  - Protein stability in stored decellularized heart valve scaffolds and diffusion
      kinetics of protective molecules.
AB  - Decellularized tissues can be used as matrix implants. The aims of this study
      were to investigate protein stability and solvent accessibility in decellularized
      pulmonary heart valve tissues. Protein denaturation profiles of tissues were
      studied by differential scanning calorimetry. Protein solvent accessibility of
      tissue exposed to D2O, and diffusion kinetics of various protective molecules
      were studied by Fourier transform infrared spectroscopy. Little changes were
      observed in the protein denaturation temperature during storage, at either 5 or
      40 degrees C. Glycerol was found to stabilize proteins; it increased the protein
      denaturation temperature. The stabilizing effect of glycerol disappeared after
      washing the sample with saline solution. Hydrogen-to-deuterium exchange rates of
      protein amide groups were fastest in leaflet tissue, followed by artery and
      muscle tissue. Diffusion of glycerol was found to be fastest in muscle tissue,
      followed by artery and leaflet tissue. Diffusion coefficients were derived and
      used to estimate the time needed to reach saturation. Fixation of tissue with
      glutaraldehyde had little effects on exchange and diffusion rates. Diffusion
      rates decreased with increasing molecular size. Proteins in decellularized heart
      valve tissue are stable during storage. Glycerol increases protein stability in a
      reversible manner. Solvent accessibility studies of protein amide groups provide
      an additional tool to study proteins in tissues. Diffusion coefficients can be
      derived to simulate diffusion kinetics of protective molecules in tissues. This
      study provides novel tools to evaluate protein stability and solvent
      accessibility in tissues, which can be used to develop biopreservation
      strategies. 

PMID- 24321315
TI  - Subglottic secretion drainage in prevention of ventilator-associated pneumonia:
      mind the gap between studies and reality.

PMID- 24321314
TI  - RHOB influences lung adenocarcinoma metastasis and resistance in a host-sensitive
      manner.
AB  - Lung adenocarcinoma (ADC) is the most common lung cancer subtype and presents a
      high mortality rate. Clinical recurrence is often associated with the emergence
      of metastasis and treatment resistance. The purpose of this study was to identify
      genes with high prometastatic activity which could potentially account for
      treatment resistance. Global transcriptomic profiling was performed by robust
      microarray analysis in highly metastatic subpopulations. Extensive in vitro and
      in vivo functional studies were achieved by overexpression and by silencing gene
      expression. We identified the small GTPase RHOB as a gene that promotes early and
      late stages of metastasis in ADC. Gene silencing of RHOB prevented metastatic
      activity in a systemic murine model of bone metastasis. These effects were highly
      dependent on tumor-host interactions. Clinical analysis revealed a marked
      association between high RHOB levels and poor survival. Consistently, high RHOB
      levels promote metastasis progression, taxane-chemoresistance, and contribute to
      the survival advantage to gamma-irradiation. We postulate that RHOB belongs to a
      novel class of "genes of recurrence" that have a dual role in metastasis and
      treatment resistance.

PMID- 24321316
TI  - Role of Rac GTPase activating proteins in regulation of NADPH oxidase in human
      neutrophils.
AB  - Precise spatiotemporal regulation of O2(-)-generating NADPH oxidases (Nox) is a
      vital requirement. In the case of Nox1-3, which depend on the small GTPase Rac,
      acceleration of GTP hydrolysis by GTPase activating protein (GAP) could represent
      a feasible temporal control mechanism. Our goal was to investigate the molecular
      interactions between RacGAPs and phagocytic Nox2 in neutrophilic granulocytes. In
      structural studies we revealed that simultaneous interaction of Rac with its
      effector protein p67(phox) and regulatory protein RacGAP was sterically possible.
      The effect of RacGAPs was experimentally investigated in a cell-free O2(-)
      generating system consisting of isolated membranes and recombinant p47(phox) and
      p67(phox) proteins. Addition of soluble RacGAPs decreased O2(-) production and
      there was no difference in the effect of four RacGAPs previously identified in
      neutrophils. Depletion of membrane-associated RacGAPs had a selective effect: a
      decrease in ARHGAP1 or ARHGAP25 level increased O2(-) production but a depletion
      of ARHGAP35 had no effect. Only membrane-localized RacGAPs seem to be able to
      interact with Rac when it is assembled in the Nox2 complex. Thus, in neutrophils
      multiple RacGAPs are involved in the control of O2(-) production by Nox2,
      allowing selective regulation via different signaling pathways. 

PMID- 24321317
TI  - A novel small molecule that induces oxidative stress and selectively kills
      malignant cells.
AB  - We have synthesized a novel molecule named XB05 (1-bromo-1,1-difluoro-non-2-yn-4
      ol) and evaluated its effects in a variety of human cell lines. XB05 displayed
      potent antiproliferative activity against cell lines derived from leukemia or
      solid tumors, but had less effect on nonmalignant cells. To identify factors that
      contribute to the cancer selectivity of XB05, we chose three cell lines that had
      high sensitivity to XB05 (U937 leukemia), moderate sensitivity (A549 lung
      cancer), or low sensitivity (Hs27 nonmalignant skin fibroblasts), and proceeded
      to assess cell death and oxidative stress in these cells. XB05 was found to
      induce cell death via both apoptotic and nonapoptotic mechanisms in U937 and A549
      cells, whereas it had no cytotoxicity against Hs27 cells at comparable
      concentrations. Treatment with XB05 caused an increase in reactive oxygen species
      in all cell lines tested, but levels were higher in malignant compared to
      nonmalignant cells. XB05 treatment also induced DNA damage exclusively in the
      malignant cells. Differences in antioxidant responses were observed between cell
      lines. For example, XB05 caused a decrease in levels of glutathione and nuclear
      Nrf2 in the most sensitive cells (U937), whereas the least sensitive cells (Hs27)
      displayed increased glutathione levels and no change in nuclear Nrf2. XB05 could
      react in vitro with cysteine and glutathione, but had much lower reactivity
      compared to typical thiol-reactive electrophiles, diethyl maleate and maleimide.
      In summary, XB05 is a novel compound that selectively kills malignant cells, most
      likely by disrupting cellular redox homeostasis, making it a promising candidate
      for development as a chemotherapeutic agent. 

PMID- 24321318
TI  - Proteome-wide profiling of carbonylated proteins and carbonylation sites in HeLa
      cells under mild oxidative stress conditions.
AB  - A number of oxidative protein modifications have been well characterized during
      the past decade. Presumably, reversible oxidative posttranslational modifications
      (PTMs) play a significant role in redox signaling pathways, whereas irreversible
      modifications including reactive protein carbonyl groups are harmful, as their
      levels are typically increased during aging and in certain diseases. Despite
      compelling evidence linking protein carbonylation to numerous disorders, the
      underlying molecular mechanisms at the proteome remain to be identified. Recent
      advancements in analysis of PTMs by mass spectrometry provided new insights into
      the mechanisms of protein carbonylation, such as protein susceptibility and exact
      modification sites, but only for a limited number of proteins. Here we report the
      first proteome-wide study of carbonylated proteins including modification sites
      in HeLa cells for mild oxidative stress conditions. The analysis relied on our
      recent strategy utilizing mass spectrometry-based enrichment of carbonylated
      peptides after DNPH derivatization. Thus a total of 210 carbonylated proteins
      containing 643 carbonylation sites were consistently identified in three
      replicates. Most carbonylation sites (284, 44.2%) resulted from oxidation of
      lysine residues (aminoadipic semialdehyde). Additionally, 121 arginine (18.8%),
      121 threonine (18.8%), and 117 proline residues (18.2%) were oxidized to reactive
      carbonyls. The sequence motifs were significantly enriched for lysine and
      arginine residues near carbonylation sites (+/-10 residues). Gene Ontology
      analysis revealed that 80% of the carbonylated proteins originated from
      organelles, 50% enrichment of which was demonstrated for the nucleus. Moreover,
      functional interactions between carbonylated proteins of kinetochore/spindle
      machinery and centrosome organization were significantly enriched. One-third of
      the 210 carbonylated proteins identified here are regulated during apoptosis. 

PMID- 24321319
TI  - Corrosion and runoff rates of Cu and three Cu-alloys in marine environments with
      increasing chloride deposition rate.
AB  - Bare copper sheet and three commercial Cu-based alloys, Cu15Zn, Cu4Sn and
      Cu5Al5Zn, have been exposed to four test sites in Brest, France, with strongly
      varying chloride deposition rates. The corrosion rates of all four materials
      decrease continuously with distance from the coast, i.e. with decreasing chloride
      load, and in the following order: Cu4Sn>Cu sheet>Cu15Zn>Cu5Al5Zn. The patina on
      all materials was composed of two main layers, Cu2O as the inner layer and
      Cu2(OH)3Cl as the outer layer, and with a discontinuous presence of CuCl in
      between. Additional minor patina constituents are SnO2 (Cu4Sn), Zn5(OH)6(CO3)2
      (Cu15Zn and Cu5Al5Zn) and Zn6Al2(OH)16CO3.4H2O/Zn2Al(OH)6Cl.2H2O/Zn5Cl2(OH)8.H2O
      and Al2O3 (Cu5Al5Zn). The observed Zn- and Zn/Al-containing corrosion products
      might be important factors for the lower sensitivity of Cu15Zn and Cu5Al5Zn
      against chloride-induced atmospheric corrosion compared with Cu sheet and Cu4Sn.
      Decreasing corrosion rates with exposure time were observed for all materials and
      chloride loads and attributed to an improved adherence with time of the outer
      patina to the underlying inner oxide. Flaking of the outer patina layer was
      mainly observed on Cu4Sn and Cu sheet and associated with the gradual
      transformation of CuCl to Cu2(OH)3Cl of larger volume. After three years only
      Cu5Al5Zn remains lustrous because of a patina compared with the other materials
      that appeared brownish-reddish. Significantly lower release rates of metals
      compared with corresponding corrosion rates were observed for all materials. Very
      similar release rates of copper from all four materials were observed during the
      fifth year of marine exposure due to an outer surface patina that with time
      revealed similar constituents and solubility properties.

PMID- 24321320
TI  - Ischaemic brain damage after cardiac arrest and induced hypothermia--a systematic
      description of selective eosinophilic neuronal death. A neuropathologic study of
      23 patients.
AB  - PURPOSE: Although well characterized in animals, brain damage in humans treated
      with hypothermia after cardiac arrest has not been systematically explored. In
      this study we aimed to describe the characteristic trait of selective
      eosinophilic neuronal death (SEND), and its correlation with time to return of
      spontaneous circulation (ROSC) in cardiac arrest patients who died after
      hypothermia treatment and were referred for autopsy. METHODS: Brain autopsy
      microscopic slides and clinical data were gathered from 23 non-survivors of
      cardiac arrest who were treated with hypothermia. Based on the percentage of
      eosinophilic neurons, a damage score 0-4 was given in 6 brain regions, and a
      total damage score was calculated. The damage score was correlated with time to
      ROSC and with neuron-specific enolase (NSE) in peripheral blood at 48 h post
      arrest. RESULTS: Hippocampus had the highest damage score with a median of 3
      (inter-quartile range 2-4) while the brainstem had the lowest median damage score
      of 0 (0-2). Total damage score showed the best correlation with time to ROSC
      (Spearman Rho=0.66). Serum NSE values >33 MUg/L (n=6) was associated with
      significantly higher mean damage score than NSE <33 MUg/L (n=9) (p=0.002).
      CONCLUSION: This is the first study to systematically describe regional SEND in
      patients treated with hypothermia after cardiac arrest. Hippocampus was the most
      vulnerable region whereas the brainstem was the most resistant. Although not
      directly compared here, the regional pattern of SEND seems not to be altered by
      hypothermia treatment, but maintains its profile distinctive for cardiac arrest
      pathogenesis.

PMID- 24321321
TI  - A comparison of actual to estimated weights in Australian children attending a
      tertiary children's' hospital, using the original and updated APLS, Luscombe and
      Owens, Best Guess formulae and the Broselow tape.
AB  - INTRODUCTION: During paediatric resuscitation it is essential to be able to
      estimate the child's weight as it determines drug doses and equipment sizes. Age
      and length-based estimations exist, with age-based estimations being especially
      useful in the preparation phase and the length-based Broselow tape having weight
      based drug doses and equipment already assigned via a colour code system. The aim
      of this study was to compare the actual recorded weights of Australian children
      to the predicted weights using the original and updated APLS, Luscombe and Owens
      and Best Guess formulae and the Broselow tape. METHOD: A retrospective
      observational study of children attending an Australian tertiary children's
      hospital. RESULTS: From 49,565 patients extracted from the database, 37,114
      children with age and weight and 37,091 children with age and height recorded
      were included in the analysis. Best Guess was the most accurate, with the
      smallest overall mean difference 0.86 kg. For <1 year old, Broselow tape was the
      most accurate (mean difference -0.43 kg), Best Guess was the most accurate for
      ages 1-5 years and 11-14 years (mean difference 0.27 and 0.20 kg respectively),
      and the updated APLS formula was the most accurate for 6-10 year-old (mean
      difference 0.42 kg). The Broselow tape was able to only classify 48.9% of
      children into the correct weight colour band. CONCLUSIONS: For an age-based
      weight estimation, in infants less than one year the new APLS formula is the most
      accurate and over one year the Best Guess formulae should be used.

PMID- 24321322
TI  - Lower incidence of unexpected in-hospital death after interprofessional
      implementation of a bedside track-and-trigger system.
AB  - BACKGROUND: In-hospital patients may suffer unexpected death because of
      suboptimal monitoring. Early recognition of deviating physiological parameters
      may enable staff to prevent unexpected in-hospital death. The aim of this study
      was to evaluate short- and long-term effects of systematic interprofessional use
      of early warning scoring, structured observation charts, and clinical algorithms
      for bedside action. METHODS: A prospective non-randomized controlled study of
      unexpected in-hospital death before and after implementation of a clinical
      intervention in a medical and surgical ward setting at an urban Danish university
      hospital. Information was obtained over three four-month study periods - a pre
      interventional one in 2009 (1st March-30th June), and two postinterventional ones
      in 2010 (1st September-31st December) and 2011 (1st March-30th June). The
      incidence of unexpected patient death, the primary study outcome, was calculated
      as the rate of unexpected patient mortality based on in-hospital risk time.
      RESULT: The adjusted unexpected patient mortality rate was significantly lower
      during the second postinterventional study period than before the intervention,
      17 versus 61 per 100 adjusted patient years (P=0.013), corresponding to a rate
      ratio of 0.271 (95% confidence interval (CI) 0.097-0.762). A tendency to reduced
      unexpected mortality was found during the first postinterventional study period
      (25 versus 61 per 100 adjusted patient years, P=0.053; rate ratio 0.404, CI 0.161
      1.012). CONCLUSION: Clinical intervention comprising systematic monitoring
      practice, early warning scoring, an observation chart, and an algorithm for
      bedside management, implemented by interprofessional teaching, training, and
      optimization of communication and collaboration, may significantly reduce
      unexpected in-hospital mortality.

PMID- 24321323
TI  - Identifying incidents of suboptimal care during paediatric emergencies-an
      observational study utilising in situ and simulation centre scenarios.
AB  - AIM: Life threatening paediatric emergencies are relatively uncommon events. When
      they do occur staff caring for these children must have the ability to recognise
      the deterioration, evaluate and simultaneously treat these patients. The aim of
      this study was to identify suboptimal care during standardised simulated
      scenarios and to identify the potential causation factors. METHODS: Participants
      were emergency department and operating theatre staff in Sydney, Australia.
      Incidents of suboptimal care were identified during scenarios and were analysed
      by thematic qualitative assessment methods. Potential causation factors were
      elicited both during and immediately after the scenarios and during facilitated
      debriefings. Causation factors were attributed to any of seven pre-defined
      categories. RESULTS: Seventy-three simulations occurred over 9 month period in
      2011. 270 doctors, 235 nurses and 11 students participated. 194 incidents of
      suboptimal care were observed and attributed to 325 causation factors. There were
      76 knowledge deficits, 39 clinical skill deficits, 36 leadership problems, 84
      communication failures, 20 poor resource utilisations, 23 preparation and
      planning failures and 47 incidents of a loss of situational awareness. Clinically
      important themes were: paediatric life support, drug choice and doses, advanced
      airway and ventilation, intravenous fluids and recognition of the deteriorating
      patient. Recurring incidents included the failure to recognise a cardiac arrest,
      inadequate fluid resuscitation and incorrect medication dose administration.
      CONCLUSIONS: During standardised paediatric simulations multiple incidents of
      suboptimal care have been identified and multiple causation factors attributed to
      these. Educators should use this information to adapt current training programs
      to encompass these factors.

PMID- 24321324
TI  - Regulation of angiotensin II type 1 receptor expression in ovarian cancer: a
      potential role for BRCA1.
AB  - BACKGROUND: Both BRCA1 and angiotensin II type 1 receptor (AGTR1) play a critical
      role in ovarian cancer progression. However, the crosstalk between BRCA1 and
      AGTR1 signaling pathways remains largely unknown. METHODS: BRCA1 promoter
      methylation was analyzed by bisulfite sequence using primers focused on the core
      promoter region. Expression levels of BRCA1 and AGTR1 were assessed by
      immunohistochemistry and real-time PCR. Regression analysis was used to examine
      the possible relationship between BRCA1 and AGTR1 protein levels. Knockdown or
      overexpression of BRCA1 was achieved by using a lentiviral vector in 293 T cells
      and SKOV3 ovarian carcinoma cells, and primary non-mutated and BRCA1-mutated
      ovarian cancer cells. RESULTS: BRCA1 dysfunction (BRCA1 mutation or
      hypermethylated BRCA1 promoter) ovarian cancer showed decreased AGTR1 levels
      compared to normal tissue. In contrast, AGTR1 expression was increased in non
      BRCA1-mutated ovarian cancer. Notably, BRCA1 activation was an effective way to
      induce AGTR1 expression in primary ovarian cancer cells and a positive
      correlation exists between BRCA1 and AGTR1 expression in human ovarian cancer
      specimens. CONCLUSIONS: These results indicate that BRCA1 may be a potential
      trigger involved in the transcriptional regulation of AGTR1 in the development of
      ovarian cancer.

PMID- 24321325
TI  - Retrospective study and immunohistochemical analysis of canine mammary sarcomas.
AB  - BACKGROUND: Canine mammary sarcomas (CMSs) are rarely diagnosed in female dogs,
      which explains the scarcity of immunohistochemical findings concerning those
      tumors. This paper presents the results of a retrospective study into CMSs and
      discusses the clinical features of the analyzed tumors, the expression of
      intermediate filaments CK, Vim, Des and alpha-SMA, and the expression of p63,
      Ki67, ERalpha, PR and p53 protein. RESULTS: Four percent of all canine mammary
      tumors (CMTs) were classified as CMSs, and they represented 5.1% of malignant
      CMTs. The mean age at diagnosis was 11.1 +/- 2.8 years. Large breed dogs were
      more frequently affected (38.7%). The majority of observed CMSs were
      fibrosarcomas (2.1%). All CMSs expressed vimentin, and higher levels of vimentin
      expression were noted in fibrosarcomas and osteosarcomas. Ki67 expression was
      significantly correlated with the grade of CMS. CONCLUSIONS: Our results revealed
      that CMSs form a heterogeneous group, therefore, immunohistochemical examinations
      could support differential and final diagnosis. Although this study analyzed a
      limited number of samples, the reported results can expand our knowledge about
      CMSs. Further work is required in this field.

PMID- 24321326
TI  - Exposure to anesthetic gases and Parkinson's disease: a case report.
AB  - BACKGROUND: The administration of anesthetics determines depression of the
      central nervous system and general anesthesia by inhalation may cause an
      environmental pollution of the operating rooms. It may therefore conceive a
      possible occupational etiology of Parkinson's Disease (PD). CASE PRESENTATION: In
      a Caucasian male aged 59 years, PD was diagnosed by brain scans with a
      presynaptic radioactive tracer of the dopaminergic system. Family history was
      negative for Parkinson's disease or essential tremor. He was a smoker, a moderate
      consumer of coffee and alcohol, and never exposed to pesticides/metals. For 30
      years (since the age of 29 until today), he worked as an anesthesiologist in
      private clinics in the Veneto (Northern Italy), exposed to anesthetic gases. The
      time elapsed from first exposure to onset of disease is 22 years, fulfilling the
      requirement of the induction/latency period. A literature search demonstrated
      unacceptable levels of anesthetic gases in public hospitals of the Veneto region
      from 1990 to 1999. This exposure was presumably high also in private hospitals of
      the region until at least 2007, when an overexposure to sevoflurane was
      repeatedly measured in this patient. The association between occupational
      exposure to anesthetic gases and risk of Parkinson's disease was supported by a
      case-control study (reporting a two-fold increase in the risk of PD associated
      with a clinical history of general anesthesia) and a cohort study comparing
      mortality from PD between US anesthesiologists and internists (showing a
      statistically significant excess (p=0.01) in anesthesiologists compared to
      internists). Numerous recent mechanistic studies (in vitro essays and in vivo
      short-term studies) strengthened the association between exposure to anesthetic
      gases (nitrous oxide, halothane, isoflurane, levoflurane) and PD. CONCLUSION: In
      view of the limited evidence of human studies and the sufficient evidence of
      experimental studies, the high exposure to anesthetic gases could have induced PD
      in the subject under study.

PMID- 24321327
TI  - Long-term cardiovascular outcomes in patients with atrial fibrillation and
      atherothrombosis in the REACH Registry.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) are at increased risk of
      thromboembolic events. The long-term prognostic implications of AF in patients
      with atherothrombosis are unknown. METHODS: We compared 4-year CV outcomes in
      patients with and without a history of AF recorded at their baseline visit in the
      REACH Registry, an international, prospective cohort of patients with established
      atherosclerotic arterial disease (CAD, CVD, PAD) or at least 3 risk factors
      (RFO). RESULTS: AF status and 4 year follow-up data were available on 44,518
      patients. The prevalence of AF at baseline was 10.3% (n=4582). Overall, patients
      with AF had approximately a 2-fold increase in the composite of CV death, MI, or
      stroke compared with patients without AF after adjustment for age, gender, prior
      ischemic event, vascular disease, congestive heart failure, diabetes, smoking,
      body mass index, region, aspirin and statin use (18.9% vs. 9.4%, p<0.0001). This
      increased risk was observed both in patients with established atherothrombosis
      (CAD: 15.5% vs. 8.0%, p=0.0001; CVD: 23.6% vs. 13.6%, p<0.0001; PAD: 24.3% vs.
      13.5%, p=0.089) and those with multiple risk factors (RFO: 12.1% vs. 5.9%,
      p=0.017). Only 52% of patients with a history of AF at baseline were receiving
      anticoagulation at 4 years. CONCLUSIONS: Patients with a history of both AF and
      atherothrombosis have particularly high long-term CV risk. Despite this increased
      risk, almost half of all patients with AF do not receive guideline recommended
      anticoagulation, highlighting an important public health priority.

PMID- 24321328
TI  - The silent sinus syndrome: protean manifestations of a rare upper respiratory
      disorder revisited.
AB  - Silent Sinus Syndrome (SSS) is known to be a rare clinical condition,
      characterized by spontaneous and progressive enophthalmos and hypoglobus
      associated with atelectasis of the maxillary sinus and alteration of the orbital
      floor. Most of the patients with this syndrome present with ophthalmological
      complaints without any nasal sinus symptoms, and it typically has a painless
      course and slow development, ergo the term "silent." Here we present a case
      report of a patient with occasional coughing spells as the presenting symptom of
      Silent Sinus Syndrome, which has not been previously described in the literature.
      The CT scan findings suggested chronic rhinosinusitis. The radiological findings
      were suggestive of maxillary sinus hypoplasia, with evidence of maxillary sinus
      atelectasis. Awareness of this syndrome is important for specialists who work
      with nasal sinus disease, since its management is different than chronic
      rhinosinusits. 

PMID- 24321329
TI  - Sequential application of chelating agents and innovative surfactants for the
      enhanced electroremediation of real sediments from toxic metals and PAHs.
AB  - This study focused on the sequential application of a chelating agent (citric
      acid) followed by a surfactant in the simultaneous electroremediation of real
      contaminated sediments from toxic metals and Polycyclic Aromatic Hydrocarbons
      (PAHs). Furthermore, the efficiency evaluation of two innovative non-ionic
      surfactants, commercially known as Poloxamer 407 and Nonidet P40, was
      investigated. The results indicated a removal efficacy of approximately 43% and
      48% for the summation of PAHs (SUM PAHs), respectively for the aforementioned
      surfactants, much better than the one obtained by the use of Tween 80 (nearly
      21%). Individual PAHs (e.g. fluorene) were removed in percentages that reached
      almost 84% and 92% in the respective electrokinetic experiments when these new
      surfactants were introduced. In addition, the combined-enhanced sequential
      electrokinetic treatment with citric acid improved dramatically the removal of Zn
      and As, compared to the unenhanced run, but did not favor the other toxic metals
      examined. Since no improvement in metal removal percentages occurred when Tween
      80 was used, significant contribution to this matter should also be attributed to
      the solubilization capacity of these innovative, in electrokinetic remediation,
      non-ionic surfactants. 

PMID- 24321330
TI  - Treatment of oil and grease in produced water by a pilot-scale constructed
      wetland system using biogeochemical processes.
AB  - Constructed wetland treatment systems (CWTSs) can effectively remove many
      constituents that limit beneficial use of oilfield produced water. The objectives
      of this investigation were: (1) to assess the effect of mass loadings of oil and
      grease (O & G) on treatment performance in pilot-scale subsurface flow and free
      water surface CWTS series having sequential reducing and oxidizing cells, and (2)
      to evaluate effects on treatment performance of adding a pilot-scale oil-water
      separator. Increase in O & G mass loading from 5 to 20 mg min(-1) caused
      decreases in both dissolved oxygen concentration and sediment redox potential,
      which affected treatment performance. Biogeochemical pathways for removal of O &
      G, iron, and manganese operate under oxidizing conditions, and removal rate
      coefficients for these constituents decreased (0.905-0.514 d(-1) for O & G, 0.773
      0.452 d(-1) for iron, and 0.970-0.518 d(-1) for manganese) because greater mass
      loading of O & G promoted reducing conditions. With increased mass loading,
      removal rate coefficients for nickel and zinc increased from 0.074 to 0.565 d(-1)
      and from 0.196 to 1.08 d(-1), respectively. Although the sequential reducing and
      oxidizing cells in the CWTS were very effective in treating the targeted
      constituents, an oil-water separator was added prior to wetland cells to enhance
      O & G removal at high inflow concentration (100 mg L(-1)). The oil-water
      separator removed approximately 50% of the O & G, and removal extents and
      efficiencies approximated those observed at 50 mg L(-1) inflow concentration
      during treatment without an oil-water separator.

PMID- 24321331
TI  - Development of USEtox characterisation factors for dishwasher detergents using
      data made available under REACH.
AB  - Because of the more and more stringent regulations and customer demand,
      dishwasher detergent manufacturers are constantly improving the composition of
      the products towards better environmental performances. In order to quantify the
      pros and cons of these changes on the lifecycle of detergents, as compared to
      conventional products, the use of Life Cycle Assessment (LCA) is a meaningful
      opportunity. However, the application of the methodology is hampered by the lack
      of Characterisation Factors (CFs) relative to the specific chemical substances
      included in the detergents composition, which cannot be included in the impact
      assessment of the effluent discharge. In this study we have tackled this problem,
      taking advantage of the specific case of three dishwasher detergents produced by
      the Chemolux/McBride group: phosphate-based, eco-labelled and phosphate-free
      formulations. Nine CFs for freshwater ecotoxicity and seven CFs for human
      toxicity have been developed, using the USEtox methodology and data made
      available under the REACH regulation. As a result, the dishwasher effluent
      composition could be characterised by more than 95% for freshwater ecotoxicity
      whereas for human toxicity the percentage was less than 36%, due to the lack of
      adequate and reliable repeated dose toxicity studies. The main contributing
      substances to freshwater ecotoxicity were found to be sodium percarbonate and
      sodium triphosphate, the latter confirming the pertinence of phosphates banning
      in the detergent industry. Regarding human toxicity, zinc shows the highest
      contribution. Further comparison to previous studies and sensitivity analysis
      substantiated the robustness of these conclusions. 

PMID- 24321332
TI  - Fates of chlorinated volatile organic compounds in aerobic biological treatment
      processes: the effects of aeration and sludge addition.
AB  - The emission of volatile organic compounds (VOCs) from wastewater treatment
      plants (WWTPs) is becoming an environmental issue of increasing concern. As
      biological treatment has been considered as one important approach for VOC
      removal, lab-scale batch experiments were conducted in this study to investigate
      the fates of four chlorinated hydrocarbons, including chloroform, carbon
      tetrachloride, trichloroethylene (TCE), and tetrachloroethylene (PERC), in the
      biological treatment processes with respect to the effects of aeration and sludge
      addition. The VOC concentrations in the phases of air, water, and sludge under
      four simulated treatment stages (the first sedimentation, the forepart and rear
      part of aerobic biological treatment, and the second sedimentation) were
      analyzed. The results were used to understand the three-phase partitioning of
      these compounds and to estimate their potentials for volatilization and
      biological sorption and degradation in these technologies with the concept of
      fugacity. It was observed that the VOCs were mainly present in the water phase
      through the experiments. The effects of aeration or sludge addition on the fates
      of these VOCs occurred but appeared to be relatively limited. The concentration
      distributions of the VOCs were well below the reported partitioning coefficients.
      It was suggested that these compounds were unsaturated in the air and sludge
      phases, enhancing their potentials for volatilization and biological
      sorption/degradation through the processes. However, the properties of these
      chlorinated VOCs such as the volatility, polarity, or even biodegradability
      caused by their structural characteristics (e.g., the number of chlorine,
      saturated or unsaturated) may represent more significant factors for their fates
      in the aerobic biological treatment processes. These findings prove the
      complication behind the current knowledge of VOC pollutions in WWTPs and are of
      help to manage the adverse impacts on the environment and public health by the
      VOCs from these particular sources. 

PMID- 24321333
TI  - Mitochondrial dysfunction induced by different concentrations of gadolinium ion.
AB  - Gadolinium-based compounds are the most widely used paramagnetic contrast agents
      in magnetic resonance imaging on the world. But the tricationic gadolinium ion
      (Gd(3+)) could induce cell apoptosis probably because of its effects on
      mitochondria. Until now, the mechanism about how Gd(3+) interacts with
      mitochondria is not well elucidated. In this work, mitochondrial swelling,
      collapsed transmembrane potential and decreased membrane fluidity were observed
      to be important factors for mitochondrial permeability transition pore (mtPTP)
      opening induced by Gd(3+). The protection effect of CsA (Cyclosporin A) could
      confirm high concentration of Gd(3+) (500 MUM) would trigger mtPTP opening.
      Moreover, mitochondrial outer membrane breakdown and volume expansion observed
      clearly by transmission electron microscopy and the release of Cyt c (Cytochrome
      c) could explain the mtPTP opening from another aspect. In addition, MBM(+)
      (monobromobimane(+)) and DTT (dithiothreitol) could protect thiol (-SH) groups
      from oxidation so that the toxicity of Gd(3+) might be resulted from the
      chelation of -SH of membrane proteins by free Gd(3+). Gd(3+) could inhibit the
      initiation of mitochondrial membrane lipid peroxidation, so it might interact
      with anionic lipids too. These findings will highly contribute to the safe
      applications of Gd-based agents.

PMID- 24321334
TI  - Impact of organic carbon and nutrients mobilized during chemical oxidation on
      subsequent bioremediation of a diesel-contaminated soil.
AB  - Remediation with in situ chemical oxidation (ISCO) impacts soil organic matter
      (SOM) and the microbial community, with deleterious effects on the latter being a
      major hurdle to coupling ISCO with in situ bioremediation (ISB). We investigate
      treatment of a diesel-contaminated soil with Fenton's reagent and modified
      Fenton's reagent coupled with a subsequent bioremediation phase of 187d, both
      with and without nutrient amendment. Chemical oxidation mobilized SOM into the
      liquid phase, producing dissolved organic carbon (DOC) concentrations 8-16 times
      higher than the untreated field sample. Higher aqueous concentrations of nitrogen
      and phosphorous species were also observed following oxidation; NH4(+) increased
      14-172 times. During the bioremediation phase, dissolved carbon and nutrient
      species were utilized for microbial growth-yielding DOC concentrations similar to
      field sample levels within 56d of incubation. In the absence of nutrient
      amendment, the highest microbial respiration rates were correlated with higher
      availability of nitrogen and phosphorus species mobilized by oxidation.
      Significant diesel degradation was only observed following nutrient amendment,
      implying that nutrients mobilized by chemical oxidation can increase microbial
      activity but are insufficient for bioremediation. While all bioremediation
      occurred in the first 28d of incubation in the biotic control microcosm with
      nutrient amendment, biodegradation continued throughout 187d of incubation
      following chemical oxidation, suggesting that chemical treatment also affects the
      desorption of organic contaminants from SOM. Overall, results indicate that
      biodegradation of DOC, as an alternative substrate to diesel, and biological
      utilization of mobilized nutrients have implications for the success of coupled
      ISCO and ISB treatments. 

PMID- 24321335
TI  - Biocompatibility and antibacterial activity of photolytic products of
      sulfonamides.
AB  - BACKGROUND: This study assessed the photochemical fate of nine sulfonamides
      (sulfamerazine, sulfanilamide, sulfamethoxypyridazine, sulfamethoxazole,
      sulfachloropyridazine, sulfamethazine, sulfadiazine, sulfathiazole and
      sulfadimethoxine) during a 6h irradiation period with UVA/UVB-light and UVA-light
      and over 7 days under natural (sunlight) conditions. The cell growth inhibition
      effect and cytotoxicity of sulfonamides and their photodegradation products was
      investigated over 24 and 48 h with murine fibroblasts and keratinocytes.
      Antibacterial activity of the degradation products was studied using the
      Geobacillus stearothermophilus var. Calidolactis C953 assay. RESULTS: UVA/UVB
      treatment of several sulfonamide solutions results in degradation of the
      compounds in different amounts with the highest degradation rate for
      sulfathiazole and sulfanilamide. The UVA/UVB light degradation products exhibit
      no antimicrobial activity. Sun light exposure over 7 days reveals a similar
      degradation pattern of the different sulfonamides, albeit to a different extent.
      Compared with UVA/UVB-irradiation, UVA-irradiated sulfonamides degrade to a
      lesser extent (except sulfamethazine). There was no impact on cell toxicity of
      the UVA/UVB-degrading products except for sulfanilamide, while a slight impact on
      cell proliferation was observed. CONCLUSIONS: All studied sulfonamides undergo
      photodegradation under UV-light exposure to a greater or lesser extent. The
      degradation products have no cytotoxic potential except sulfanilamide and have a
      slight impact on cell proliferation. All degradation products showed no
      antibacterial activity. Thus, UV-light exposure seems to represent an adequate
      method for inactivating sulfonamides with regard to their antimicrobial activity.

PMID- 24321336
TI  - The effects of rhodium on the renal function of female Wistar rats.
AB  - In recent years, the increased use of rhodium (Rh) as an active catalyst material
      in modern three-way automobile catalytic converters has led to a parallel rise in
      environmental levels of this metal. In spite of this, the literature contains few
      studies of the effects of Rh on human health. The aim of this study is to assess
      the effects of Rh on the renal function of female Wistar rats. Our findings show
      that sub-acute exposure to six increasing concentrations, ranging from 0.001 to 1
      mg L(-1), of Rh (III) chloride hydrate in drinking water does not induce
      alterations in urinary albumin levels, while, at concentrations from 0.1 to 1 mg
      L(-1), a significant rise in urinary levels of Retinol Binding Protein is evident
      and an increasing trend in urinary beta2-microglobulin, which becomes significant
      at 1 mg L(-1), is observed. These results therefore demonstrate a nephrotoxic
      action of Rh at tubular level in a wide range of doses. Interestingly, because of
      the recent increase in environmental Rh levels, these findings may have relevant
      implications both for occupationally exposed subjects and for the general
      population, especially children.

PMID- 24321337
TI  - Autonomous exercise game use improves metabolic control and quality of life in
      type 2 diabetes patients - a randomized controlled trial.
AB  - BACKGROUND: Lifestyle intervention in type 2 diabetes mellitus (T2DM) is
      effective but needs a special local setting and is costly. Therefore, in a
      randomized-controlled trial we tested the hypothesis that the autonomous use of
      the interactive exercise game Wii Fit Plus over a period of 12 weeks improves
      metabolic control, with HbA1c reduction as the primary outcome, and weight loss,
      reduction of cardiometabolic risk factors, physical activity and quality of life
      (secondary outcomes) in T2DM patients. METHODS: Participants (n = 220) were
      randomized into an intervention and a control group. The intervention group was
      provided with a Wii console, a balance board and the exercise game Wii Fit Plus
      for 12 weeks. The control group remained under routine care and received the
      items 12 weeks later. At baseline and after 12 weeks (and for the control group
      additionally after 12 weeks of intervention) the participants' health parameters,
      medication, physical activity and validated questionnaires for quality of life
      (PAID, SF12, WHO-5, CES-D) were requested and compared in a complete case
      analysis using the Mann-Whitney test and the Wilcoxon signed rank test. RESULTS:
      80% of participants completed the 12-week study. Patients in the intervention
      group significantly improved HbA1c (from 7.1 +/- 1.3% to 6.8 +/- 0.9%; -0.3 +/-
      1.1%; p = 0.0002) in comparison to the control group (from 6.8 +/- 0.9% to 6.7 +/
      0.7%; -0.1 +/- 0.5%) and also significantly reduced fasting blood glucose (from
      135.8 +/- 38.9 mg/dl to 126.6 +/- 36.6 mg/dl; p = 0.04), weight (from 97.6 +/-
      19.2 kg to 96.3 +/- 18.7 kg; p < 0.001) and body mass index (from 34.1 +/- 6.5
      kg/m2 to 33.5 +/- 6.5 kg/m2; p < 0.001). Daily physical activity increased
      significantly (p < 0.001). Diabetes-dependent impairment, mental health,
      subjective wellbeing and quality of life also improved significantly, and the
      number of patients with depression decreased. Similar improvements were seen in
      the control group after exercise game intervention. CONCLUSIONS: In this trial a
      low-threshold intervention with the interactive exercise game Wii Fit Plus was
      able to motivate T2DM patients to improve physical activity, glucometabolic
      control and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735643.

PMID- 24321338
TI  - Time course of systemic oxidative stress and inflammatory response induced by an
      acute exposure to Residual Oil Fly Ash.
AB  - It is suggested that systemic oxidative stress and inflammation play a central
      role in the onset and progression of cardiovascular diseases associated with the
      exposure to particulate matter (PM). The aim of this work was to evaluate the
      time changes of systemic markers of oxidative stress and inflammation, after an
      acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were
      intranasally instilled with a ROFA suspension (1.0mg/kg body weight) or saline
      solution, and plasma levels of oxidative damage markers [thiobarbituric acid
      reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced
      (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide
      dismutase (SOD) activity], cytokines levels, and intravascular leukocyte
      activation were evaluated after 1, 3 or 5h of exposure. Oxidative damage to
      lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early
      as 1h. Afterwards, increased protein oxidation, decreased ascorbic acid content
      and SOD activity were found in this group at 3h. The onset of an adaptive
      response was observed at 5h after the ROFA exposure, as indicated by decreased
      TBARS plasma content and increased SOD activity. The observed increase in
      oxidative damage to plasma macromolecules, together with systemic antioxidants
      depletion, may be a consequence of a systemic inflammatory response triggered by
      the ROFA exposure, since increased TNF-alpha and IL-6 plasma levels and
      polymorphonuclear leukocytes activation was found at every evaluated time point.
      These findings contribute to the understanding of the increase in cardiovascular
      morbidity and mortality, in association with environmental PM inhalation. 

PMID- 24321339
TI  - Precision-cut liver slices as a model for the early onset of liver fibrosis to
      test antifibrotic drugs.
AB  - Induction of fibrosis during prolonged culture of precision-cut liver slices
      (PCLS) was reported. In this study, the use of rat PCLS was investigated to
      further characterize the mechanism of early onset of fibrosis in this model and
      the effects of antifibrotic compounds. Rat PCLS were incubated for 48h, viability
      was assessed by ATP and gene expression of PDGF-B and TGF-beta1 and the fibrosis
      markers Hsp47, alphaSma and Pcol1A1 and collagen1 protein expressions were
      determined. The effects of the antifibrotic drugs imatinib, sorafenib and
      sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic
      acid, tetrandrine and pirfenidone, TGFbeta-pathway inhibitors, were determined.
      After 48h of incubation, viability of the PCLS was maintained and gene expression
      of PDGF-B was increased while TGF-beta1 was not changed. Hsp47, alphaSma and
      Pcol1A1 gene expressions were significantly elevated in PCLS after 48h, which was
      further increased by PDGF-BB and TGF-beta1. The increased gene expression of
      fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFbeta
      inhibitors showed marginal effects. The protein expression of collagen 1 was
      inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion,
      the increased gene expression of PDGF-B and the down-regulation of fibrosis
      markers by PDGF-pathway inhibitors, together with the absence of elevated TGF
      beta1 gene expression and the limited effect of the TGFbeta-pathway inhibitors,
      indicated the predominance of the PDGF pathway in the early onset of fibrosis in
      PCLS. PCLS appear a useful model for research of the early onset of fibrosis and
      for testing of antifibrotic drugs acting on the PDGF pathway. 

PMID- 24321340
TI  - Autophagy blockade sensitizes the anticancer activity of CA-4 via JNK-Bcl-2
      pathway.
AB  - Combretastatin A-4 (CA-4) has already entered clinical trials of solid tumors
      over ten years. However, the limited anticancer activity and dose-dependent
      toxicity restrict its clinical application. Here, we offered convincing evidence
      that CA-4 induced autophagy in various cancer cells, which was demonstrated by
      acridine orange staining of intracellular acidic vesicles, the degradation of
      p62, the conversion of LC3-I to LC3-II and GFP-LC3 punctate fluorescence.
      Interestingly, CA-4-mediated apoptotic cell death was further potentiated by
      pretreatment with autophagy inhibitors (3-methyladenine and bafilomycin A1) or
      small interfering RNAs against the autophagic genes (Atg5 and Beclin 1). The
      enhanced anticancer activity of CA-4 and 3-MA was further confirmed in the SGC
      7901 xenograft tumor model. These findings suggested that CA-4-elicited
      autophagic response played a protective role that impeded the eventual cell death
      while autophagy inhibition was expected to improve chemotherapeutic efficacy of
      CA-4. Meanwhile, CA-4 treatment led to phosphorylation/activation of JNK and JNK
      dependent phosphorylation of Bcl-2. Importantly, JNK inhibitor or JNK siRNA
      inhibited autophagy but promoted CA-4-induced apoptosis, indicating a key
      requirement of JNK-Bcl-2 pathway in the activation of autophagy by CA-4. We also
      identified that pretreatment of Bcl-2 inhibitor (ABT-737) could significantly
      enhance anticancer activity of CA-4 due to inhibition of autophagy. Taken
      together, our data suggested that the JNK-Bcl-2 pathway was considered as the
      critical regulator of CA-4-induced protective autophagy and a potential drug
      target for chemotherapeutic combination. 

PMID- 24321341
TI  - Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic
      programming alteration in second generation rats.
AB  - Our previous studies have demonstrated that prenatal caffeine ingestion induces
      an increased susceptibility to metabolic syndrome with alterations of glucose and
      lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth
      retardation (IUGR) rats, and the underlying mechanism is originated from a
      hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic
      programming alteration in utero. This study aims to investigate the
      transgenerational effects of this programming alteration in adult second
      generation (F2). Pregnant Wistar rats were administered with caffeine
      (120mg/kg.d) from gestational day 11 until delivery. Four groups in F2 were set
      according to the cross-mating between control and caffeine-induced IUGR rats. F2
      were subjected to a fortnight ice water swimming stimulus on postnatal month 4,
      and blood samples were collected before and after stress. Results showed that the
      majority of the activities of HPA axis and phenotypes of glucose and lipid
      metabolism were altered in F2. Particularly, comparing with the control group,
      caffeine groups had an enhanced corticosterone levels after chronic stress.
      Compared with before stress, the serum glucose levels were increased in some
      groups whereas the triglyceride levels were decreased. Furthermore, total
      cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol
      gain rates were decreased in most caffeine groups after stress. These
      transgenerational effects were characterized partially with gender and parental
      differences. Taken together, these results indicate that the reproductive and
      developmental toxicities and the neuroendocrine metabolic programming mechanism
      by prenatal caffeine ingestion have transgenerational effects in rats, which may
      help to explain the susceptibility to metabolic syndrome and associated diseases
      in F2. 

PMID- 24321343
TI  - Cytotoxic activity of gypenosides and gynogenin against non-small cell lung
      carcinoma A549 cells.
AB  - The activity of gypenosides and gynogenin of Gynostemma pentaphyllum against non
      small cell lung carcinoma (NSCLC) A549 cells was investigated to identify the
      structural characteristics of gypenosides and gynogenin to have anti-NSCLC
      activity. Of the tested dammarane-type compounds, 20S-dammar-24-en
      2alpha,3beta,12beta,20-tetrol showed the strongest activity against A549 cells.
      Based on the structure and cytotoxic activity relationships of gypenosides and
      gynogenin, the OH group in C-2, the connected sugar number and the configuration
      in C-20 were important for cytotoxic activity against A549 cells. 

PMID- 24321342
TI  - The inhibitory and combinative mechanism of HZ08 with P-glycoprotein expressed on
      the membrane of Caco-2 cell line.
AB  - Recently, the research and development of agents to reverse the phenomenon of
      multidrug resistance has been an attractive goal as well as a key approach to
      elevating the clinical survival of cancer patients. Although three generations of
      P-glycoprotein modulators have been identified, poor clearance and metabolism
      render these agents too toxic to be used in clinical application. HZ08, which has
      been under investigation for several years, shows a dramatic reversal effect with
      low cytotoxicity. For the first time, we aimed to describe the interaction
      between HZ08 and P-glycoprotein in Caco-2 cell line in which P-glycoprotein is
      overexpressed naturally. Cytotoxicity and multidrug resistance reversal assays,
      together with flow cytometry, fluorescence microscopy and siRNA interference as
      well as Caco-2 monolayer transport model were employed in this study to evaluate
      the interaction between HZ08 and P-glycoprotein. This study revealed that HZ08
      was capable of reversing adriamycin resistance mediated by P-glycoprotein as a
      result of intracellular enhancement of adriamycin accumulation, which was found
      to be superior to verapamil. In addition, we confirmed that HZ08 suppressed the
      transport of Rhodamine123 in the Caco-2 monolayer model but had little effect on
      P-glycoprotein expression. The transport of HZ08 was diminished by P-glycoprotein
      inhibitors (verapamil and LY335979) and its accumulation was increased via siRNA
      targeting MDR1 in Caco-2 cells. Furthermore, considering the binding site of P
      glycoprotein, verapamil performed as a competitive inhibitor with HZ08. In
      conclusion, as a P-glycoprotein substrate, HZ08 inhibited P-glycoprotein activity
      and may share the same binding site of verapamil to P-glycoprotein. 

PMID- 24321344
TI  - Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin
      (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands.
AB  - The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2
      and 3, were synthesized employing highly enantioselective PTC alkylation and
      evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the
      eutomer in binding affinity and functional activity. The agonism of compound 2R
      was comparable to that of RTX. Docking analysis of the chiral isomers of 3
      suggested the basis for its stereospecific activity and the binding mode of 3R. 

PMID- 24321345
TI  - Preparation and evaluation of deconstruction analogues of 7-deoxykalafungin as
      AKT kinase inhibitors.
AB  - The pyranonaphthoquinone (PNQ) lactone natural products, including 7
      deoxykalafungin, have been reported to be potent and selective covalent
      inhibitors of AKT kinase. In this work we seek to identify structural features of
      the natural product scaffold that are essential for potency and selectivity.
      Using a deconstruction approach, we designed and prepared simplified analogues of
      7-deoxykalafungin. Testing of the compounds for their ability to inhibit AKT and
      the closely related kinase PKA revealed that the 3,6-dihydro-2H-pyran ring of the
      PNQ lactones is required for potent and selective inhibition of AKT. We have also
      unexpectedly identified a new submicromolar inhibitor of PKA. 

PMID- 24321346
TI  - The triadic systems model perspective and adolescent risk taking.
AB  - In this special issue, Ernst (2014) outlines the triadic systems model, which
      focuses on the balanced interaction among three functional neural systems: the
      prefrontal cortex (regulation/control), striatum (motivation/approach), and
      amygdala (emotion/avoidance). Asynchrony in maturation timelines, coupled with
      less mature connectivity across brain regions, is thought to result in unique
      vulnerabilities for risk taking during the adolescent age period. Yet, the
      research evidence linking the triadic systems model to differences in risk taking
      across adolescence and adulthood is equivocal, and few studies have examined how
      neural development is associated with real-world behavior. In this commentary, we
      outline research on adolescent risk taking which highlights the importance of
      considering trait level and situational conditions when examining associations
      between neural systems and behavior, as well as the need to adopt a lifespan
      perspective. 

PMID- 24321347
TI  - Successful bioremediation of an aged and heavily contaminated soil using a
      microbial/plant combination strategy.
AB  - Bioremediation of an aged and heavily contaminated soil was performed using
      microbial remediation, phytoremediation, and microbial/phytoremediation. The
      removal efficiency of polycyclic aromatic hydrocarbons (PAHs) was in the order
      microbial/phytoremediation>microbial remediation~phytoremediation>control. The
      removal percentage of microbial/phytoremediation (69.6%) was twice that of
      control. Kocuria sp. P10 significantly enhanced PAH removal (P<0.05) and ryegrass
      growth (P<0.01). Dehydrogenase activity increased steadily and was negatively
      correlated with total PAH content. Successional changes in soil microbial
      communities were also detected by pyrosequencing. The results indicated that
      biodiversity of the soil bacterial community gradually increased with time and
      was slightly lower in control, as indicated by operational taxonomic unit (OTU)
      numbers and Shannon-Wiener indices. Proportions of Betaproteobacteria and
      Gammaproteobacteria were consistently high in all groups. Actinobacteridae were
      initially predominant (>37.8%) but rapidly decreased to <4%. The proportions of
      Acidobacteria increased greatly and this increase was positively correlated with
      PAH removal. These findings indicate a healthy ecological progression and a role
      of Acidobacteria as an indicator of the process. This study provides new insights
      into the dynamics of community structure during bioremediation process and a
      possible basis for ecological assessment for bioremediation on a large scale. 

PMID- 24321348
TI  - Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient
      vascular embolization.
AB  - Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for
      biomedical applications were readily prepared from poly(lactide-co-glycolide)
      (PLGA)-poly(ethylene glycol) (PEG)-PLGA crosslinker and PEGMA as a monomer using
      a suspension polymerization process. Additional co-monomers, methacrylic acid and
      2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation
      to improve the properties of the microspheres. All synthesized microspheres were
      spherical in shape, calibrated in the 300-500 MUm range, swelled in phosphate
      buffered saline (PBS) and easily injectable through a microcatheter. Hydrolytic
      degradation experiments performed in PBS at 37  degrees C showed that all of the
      formulations tested were totally degraded in less than 2 days. The resulting
      degradation products were a mixture of low-molecular-weight compounds (PEG,
      lactic and glycolic acids) and water-soluble polymethacrylate chains having
      molecular weights below the threshold for renal filtration of 50 kg mol(-1) for
      the microspheres containing MDO. Both the microspheres and the degradation
      products were determined to exhibit minimal cytotoxicity against L929
      fibroblasts. Additionally, in vivo implantation in a subcutaneous rabbit model
      supported the in vitro results of a rapid degradation rate of microspheres and
      provided only a mild and transient inflammatory reaction comparable to that of
      the control group.

PMID- 24321350
TI  - A tyrosine-rich amelogenin peptide promotes neovasculogenesis in vitro and ex
      vivo.
AB  - The formation of new blood vessels has been shown to be fundamental in the repair
      of many damaged tissues, and we have recently shown that the adult human
      periodontal ligament contains multipotent stem/progenitor cells that are capable
      of undergoing vasculogenic and angiogenic differentiation in vitro and ex vivo.
      Enamel matrix protein (EMP) is a heterogeneous mixture of mainly amelogenin
      derived proteins produced during tooth development and has been reported to be
      sometimes effective in stimulating these processes, including in clinical
      regeneration of the periodontal ligament. However, the identity of the specific
      bioactive component of EMP remains unclear. In the present study we show that,
      while the high-molecular-weight Fraction A of enamel matrix derivative (a heat
      treated form of EMP) is unable to stimulate the vasculogenic differentiation of
      human periodontal ligament cells (HPC) in vitro, the low-molecular-weight
      Fraction C significantly up-regulates the expression of the endothelial markers
      VEGFR2, Tie-1, Tie-2, VE-cadherin and vWF and markedly increases the
      internalization of low-density lipoprotein. Furthermore, we also demonstrate, for
      the first time, that the synthetic homolog of the 45-amino acid tyrosine-rich
      amelogenin peptide (TRAP) present in Fraction C is likely to be responsible for
      its vasculogenesis-inducing activity. Moreover, the chemically synthesized TRAP
      peptide is also shown here to be capable of up-regulating the angiogenic
      differentiation of the HPC, based on its marked stimulation of in vitro cell
      migration and tubule formation and of blood vessel formation assay in a chick
      embryo chorioallantoic membrane model ex vivo. This novel peptide, and modified
      derivatives, might thereby represent a new class of regenerative drug that has
      the ability to elicit new blood vessel formation and promote wound healing in
      vivo. 

PMID- 24321351
TI  - Design of a composite biomaterial system for tissue engineering applications.
AB  - Biomaterials that regulate vascularized tissue formation have the potential to
      contribute to new methods of tissue replacement and reconstruction. The goal of
      this study was to develop a porous, degradable tissue engineering scaffold that
      could deliver multiple growth factors and regulate vessel assembly within the
      porous structure of the material. Porous hydrogels of poly(ethylene glycol)-co-(L
      lactic acid) (PEG-PLLA) were prepared via salt leaching. The degradation time of
      the hydrogels could be controlled between 1 and 7 weeks, based on hydrogel
      composition. Fibrin was incorporated into the interconnected pores of the
      hydrogels to promote neovascularization and as a reservoir for rapid (<5 days)
      growth factor delivery. Poly(lactic-co-glycolic acid) (PLGA) microspheres were
      incorporated into the degradable polymeric hydrogel scaffold to allow sustained
      (>30 days) growth factor delivery. Fibroblast growth factor-1 (FGF-1) and
      platelet-derived growth factor-BB (PDGF-BB) were delivered from the system owing
      to their roles in the promotion of angiogenesis and vascular stabilization,
      respectively. Hydrogels tested in vivo with a subcutaneous implantation model
      were selected based on the results from in vitro degradation and growth factor
      release kinetics. Dual growth factor delivery promoted significantly more tissue
      ingrowth in the scaffold compared with blank or single growth factor delivery.
      The sequential delivery of FGF-1 following PDGF-BB promoted more persistent and
      mature blood vessels. In conclusion, a biomaterials system was developed to
      provide structural support for tissue regeneration, as well as delivery of growth
      factors that stimulate neovascularization within the structure prior to complete
      degradation.

PMID- 24321352
TI  - Risk factors and treatment outcomes of bloodstream infection caused by extended
      spectrum cephalosporin-resistant Enterobacter species in adults with cancer.
AB  - Treatment of Enterobacter infection is complicated due to its intrinsic
      resistance to cephalosporins. Medical records of 192 adults with cancer who had
      Enterobacter bacteremia were analyzed retrospectively to evaluate the risk
      factors for and the treatment outcomes in extended-spectrum cephalosporin (ESC)
      resistant Enterobacter bacteremia in adults with cancer. The main outcome measure
      was 30-day mortality. Of the 192 patients, 53 (27.6%) had bloodstream infections
      caused by ESC-resistant Enterobacter species. Recent use of a third-generation
      cephalosporin, older age, tumor progression at last evaluation, recent surgery,
      and nosocomial acquisition were associated with ESC-resistant Enterobacter
      bacteremia. The 30-day mortality rate was significantly higher in the resistant
      group. Multivariate analysis showed that respiratory tract infection, tumor
      progression, septic shock at presentation, Enterobacter aerogenes as the culprit
      pathogen, and diabetes mellitus were independent risk factors for mortality. ESC
      resistance was significantly associated with mortality in patients with E.
      aerogenes bacteremia, although not in the overall patient population. 

PMID- 24321353
TI  - Characterization of variables that may influence ozenoxacin in susceptibility
      testing, including MIC and MBC values.
AB  - Ozenoxacin is a new des-fluoro-(6)-quinolone active against pathogens involved in
      skin and skin structure infections, including Gram-positives resistant to
      fluoroquinolones. The in vitro bacteriostatic and bactericidal activity of
      ozenoxacin, ciprofloxacin, and levofloxacin was studied against 40 clinical
      isolates and 16 ATCC quality control strains under different test conditions,
      including cation supplementation, pH, inoculum size, inoculum preparation,
      incubation time, human serum, and CO2 incubation. The activity of ozenoxacin was
      unaffected by cation test medium supplementation, inoculum preparation,
      incubation time, and the increasing CO2 environment. On the contrary, ozenoxacin
      activity decreased by high inoculum (10(7) CFU/mL), increased presence of human
      serum in the medium, and increased pH. The last effect was different for
      ciprofloxacin and levofloxacin, which decreased activity when pH decreased. The
      bactericidal mode of action of ozenoxacin and control drugs was consistently
      maintained (MBC/MIC ratios <=4) in spite of variations of their activity under
      different test conditions. 

PMID- 24321349
TI  - Ability of new obturation materials to improve the seal of the root canal system:
      a review.
AB  - New obturation biomaterials have been introduced over the past decade to improve
      the seal of the root canal system. However, it is not clear whether they have
      really produced a three-dimensional impervious seal that is important for
      reducing diseases associated with root canal treatment. A review of the
      literature was performed to identify models that have been employed for
      evaluating the seal of the root canal system. In vitro and in vivo models are not
      totally adept at quantifying the seal of root canals obturated with classic
      materials. Thus, one has to resort to clinical outcomes to examine whether there
      are real benefits associated with the use of recently introduced materials for
      obturating root canals. However, there is no simple answer because endodontic
      treatment outcomes are influenced by a host of other predictors that are more
      likely to take precedence over the influence of obturation materials. From the
      perspective of clinical performance, classic root filling materials have stood
      the test of time. Because many of the recently introduced materials are so new,
      there is not enough evidence yet to support their ability to improve clinical
      performance. This emphasizes the need to translate anecdotal information into
      clinically relevant research data on new biomaterials. 

PMID- 24321354
TI  - Performance characteristics and clinical predictive value of the string test for
      detection of hepato-virulent Klebsiella pneumoniae isolated from blood cultures.
AB  - This study evaluated the phenotypic string test for identifying Klebsiella
      pneumoniae bacteraemic isolates associated with primary liver abscess. Test
      reproducibility and repeatability exceeded 95%, with varying sensitivity (66-90%)
      and specificity (64-67%) depending on cut-off values. The positive predictive
      value of a positive string test for identifying hepato-virulent isolates was
      <35%. 

PMID- 24321355
TI  - Genetic characterization of Staphylococcus aureus isolates causing bloodstream
      infections in Austria.
AB  - A total of 112 Staphylococcus aureus bloodstream isolates were genetically
      characterized. Spa typing and DNA microanalysis exhibited high diversity,
      resulting in 64 different spa types and 9 different SplitsTree clusters.
      Methicillin-resistant S. aureus (MRSA) were found in 6 cases only, including the
      first case of life-stock-associated MRSA (MRSA ST398) in bloodstream infection in
      Austria. 

PMID- 24321356
TI  - Therapeutic effects of garenoxacin in murine experimental secondary pneumonia by
      Streptococcus pneumoniae after influenza virus infection.
AB  - In a pneumococcal pneumonia murine model following influenza virus infection,
      garenoxacin was more effective than other fluoroquinolones and demonstrated high
      levels of bacterial eradication in the lung, low mortality, and potent
      histopathological improvements. Garenoxacin could potentially be used for the
      treatment of secondary pneumococcal pneumonia following influenza. 

PMID- 24321357
TI  - Multicenter validation of the VITEK MS v2.0 MALDI-TOF mass spectrometry system
      for the identification of fastidious gram-negative bacteria.
AB  - The VITEK MS v2.0 MALDI-TOF mass spectrometry system's performance in identifying
      fastidious gram-negative bacteria was evaluated in a multicenter study. Compared
      with the reference method (DNA sequencing), the VITEK MS system provided an
      accurate, species-level identification for 96% of 226 isolates; an additional 1%
      were accurately identified to the genus level. 

PMID- 24321358
TI  - Outcome accuracy of the Emergency Medical Dispatcher's initial selection of a
      diabetic problems protocol.
AB  - INTRODUCTION: Diabetes mellitus, although a chronic disease, also can cause
      acute, sudden symptoms requiring emergency intervention. In these cases,
      Emergency Medical Dispatchers (EMDs) must identify true diabetic complaints in
      order to determine the correct care. In 911 systems utilizing the Medical
      Priority Dispatch System (MPDS), International Academies of Emergency Dispatch
      certified EMDs determine a patient's chief complaint by matching the caller's
      response to an initial pre-scripted question to one of 37 possible chief
      complaints protocols. The ability of EMDs to identify true diabetic-triggered
      events reported through 911 has not been studied. OBJECTIVE: The primary
      objective of this study was to determine the percentage of EMD-recorded patient
      cases (using the Diabetic Problems protocol in the MPDS) that were confirmed by
      either attending paramedics or the hospital as experiencing a diabetic-triggered
      event. METHODS: This was a retrospective study involving six hospitals, one fire
      department, and one ambulance service in Salt Lake City, Utah USA. Dispatch data
      for one year recorded under the Diabetic Problems protocol, along with the
      associated paramedic and hospital outcome data, were reviewed/analyzed. The
      outcome measures were: the percentage of cases that had diabetic history,
      percentage of EMD-identified diabetic problems cases that were confirmed by
      Emergency Medical Services (EMS) and/or hospital records as true diabetic
      triggered events, and percentage of EMD-identified diabetic patients who also had
      other medical conditions. A diabetic-triggered event was defined as one in which
      the patient's emergency was directly caused by diabetes or its medical
      management. Descriptive statistics were used for categorical measures and
      parametric statistical methods assessed the differences between study groups, for
      continuous measures. RESULTS: Three-hundred ninety-three patient cases were
      assigned to the Diabetic Problems Chief Complaint protocol. Of the 367 (93.4%)
      patients who had a documented history of diabetes, 279 (76%) were determined to
      have had a diabetic-triggered event. However, only 12 (3.6%) initially assigned
      to this protocol did not have a confirmed history of diabetes. CONCLUSIONS: Using
      the MPDS to select the Diabetic Problems Chief Complaint protocol, the EMDs
      correctly identified a true diabetic-triggered event the majority of the time.
      However, many patients had other medical conditions, which complicated the
      initial classification of true diabetic-triggered events. Future studies should
      examine the associations between the five specific Diabetic Problems Chief
      Complaint protocol determinant codes (triage priority levels) and severity
      measures, eg, blood sugar level and Glasgow Coma Score.

PMID- 24321359
TI  - Management of adults with paediatric-onset chronic liver disease: strategic
      issues for transition care.
AB  - Advances in the management of children with chronic liver disease have enabled
      many to survive into adulthood with or without their native livers, so that the
      most common of these conditions are becoming increasingly common in adult
      hepatology practice. Because the aetiologies of chronic liver disease in children
      may vary significantly from those in adulthood, adults with paediatric-onset
      chronic liver disease may often present with clinical manifestations unfamiliar
      to their adulthood physician. Transition of medical care to adult practice
      requires that the adulthood medical staff (primary physicians and subspecialists)
      have a comprehensive knowledge of childhood liver disease and their implications,
      and of the differences in caring for these patients. Pending still unavailable
      Scientific Society guidelines, this article examines causes, presentation modes,
      evaluation, management, and complications of the main paediatric-onset chronic
      liver diseases, and discusses key issues to aid in planning a program of
      transition from paediatric to adult patients. 

PMID- 24321360
TI  - Exploring the "dark matter" of a mammalian proteome by protein structure and
      function modeling.
AB  - BACKGROUND: A growing body of evidence shows that gene products encoded by short
      open reading frames play key roles in numerous cellular processes. Yet, they are
      generally overlooked in genome assembly, escaping annotation because small
      protein-coding genes are difficult to predict computationally. Consequently,
      there are still a considerable number of small proteins whose functions are yet
      to be characterized. RESULTS: To address this issue, we apply a collection of
      structural bioinformatics algorithms to infer molecular function of putative
      small proteins from the mouse proteome. Specifically, we construct 1,743
      confident structure models of small proteins, which reveal a significant
      structural diversity with a noticeably high helical content. A subsequent
      structure-based function annotation of small protein models exposes 178,745
      putative protein-protein interactions with the remaining gene products in the
      mouse proteome, 1,100 potential binding sites for small organic molecules and 987
      metal-binding signatures. CONCLUSIONS: These results strongly indicate that many
      small proteins adopt three-dimensional structures and are fully functional,
      playing important roles in transcriptional regulation, cell signaling and
      metabolism. Data collected through this work is freely available to the academic
      community at http://www.brylinski.org/content/databases to support future studies
      oriented on elucidating the functions of hypothetical small proteins.

PMID- 24321361
TI  - The time-course of alpha neurofeedback training effects in healthy participants.
AB  - The time-course of alpha neurofeedback training (NFT) was investigated in 18
      healthy participants who received 15 sessions of training (eyes open), each
      consisting of three training periods (data are from Van Boxtel et al., 2012).
      Here we report on the within- and between-session training effects using
      multilevel analyses. Over sessions, total alpha power (8-12 Hz) increased up to
      the tenth session, after which low alpha power (8-10 Hz) remained at the same
      level, while high alpha power (10-12 Hz) decreased. Within each training session,
      total alpha power increased from the first to the second period, and then
      decreased again. This decrease, however, was caused by a decrease in high alpha
      power only; low alpha power remained up to the end of training. These effects are
      discussed in terms of attention and motivation, and suggest different
      trainability for low and high alpha power.

PMID- 24321362
TI  - Disgust, but not anger provocation, enhances levator labii superioris activity
      during exposure to moral transgressions.
AB  - Physical disgust is elicited by, and amplifies responses to, moral
      transgressions, suggesting that moral disgust may be a biologically expanded form
      of physical disgust. However, there is limited research comparing the effects of
      physical disgust to that of other emotions like anger, making it difficult to
      determine if the link between disgust and morality is unique. The current
      research evaluated the specificity of the relationship between disgust and
      morality by comparing links with anger, using state, physiological and trait
      measures of emotionality. Participants (N=90) were randomly allocated to have
      disgust, anger or no emotion induced. Responses to images depicting moral,
      negative non-moral, and neutral themes were then recorded using facial
      electromyography. Inducing disgust, but not anger, increased psychophysiological
      responses to moral themes. Trait disgust, but not trait anger, correlated with
      levator labii responses to moral themes. These findings provide strong evidence
      of a unique link between physical disgust and morality. 

PMID- 24321363
TI  - Evaluation of neurofeedback in ADHD: the long and winding road.
AB  - Among the clinical applications of neurofeedback, most research has been
      conducted in ADHD. As an introduction a short overview of the general history of
      neurofeedback will be given, while the main part of the paper deals with a review
      of the current state of neurofeedback in ADHD. A meta-analysis on neurofeedback
      from 2009 found large effect sizes for inattention and impulsivity and medium
      effects sizes for hyperactivity. Since 2009 several new studies, including 4
      placebo-controlled studies, have been published. These latest studies are
      reviewed and discussed in more detail. The review focuses on studies employing
      (1) semi-active, (2) active, and (3) placebo-control groups. The assessment of
      specificity of neurofeedback treatment in ADHD is discussed and it is concluded
      that standard protocols such as theta/beta, SMR and slow cortical potentials
      neurofeedback are well investigated and have demonstrated specificity. The paper
      ends with an outlook on future questions and tasks. It is concluded that future
      controlled clinical trials should, in a next step, focus on such known protocols,
      and be designed along the lines of learning theory. 

PMID- 24321364
TI  - Twenty years of functional near-infrared spectroscopy: introduction for the
      special issue.
AB  - Papers from four different groups were published in 1993 demonstrating the
      ability of functional near infrared spectroscopy (fNIRS) to non-invasively
      measure hemoglobin concentration responses to brain function in humans. This
      special issue commemorates the first 20years of fNIRS research. The 9 reviews and
      49 contributed papers provide a comprehensive survey of the exciting advances
      driving the field forward and of the myriad of applications that will benefit
      from fNIRS. 

PMID- 24321365
TI  - Three-dimensional anatomy of equine incisors: tooth length, enamel cover and age
      related changes.
AB  - BACKGROUND: Equine incisors are subjected to continuous occlusal wear causing
      multiple, age related changes of the extragingival crown. It is assumed that the
      occlusal wear is compensated by continued tooth elongation at the apical ends of
      the teeth. In this study, MUCT-datasets offered the opportunity to analyze the
      three-dimensional appearance of the extra- and intraalveolar parts of the enamel
      containing dental crown as well as of the enamel-free dental root. Multiple
      morphometric measurements elucidated age related, morphological changes within
      the intraalveolar part of the incisors. RESULTS: Equine incisors possess a unique
      enamel cover displaying large indentations on the mesial and distal sides. After
      eruption tooth elongation at the apical end outbalances occlusal wear for two to
      four years resulting in increasing incisor length in this period of time.
      Remarkably, this maximum length is maintained for about ten years, up to a tooth
      age of 13 to 15 years post eruption. Variances in the total length of individual
      teeth are related to different Triadan positions (central-, middle- and corner
      incisors) as well as to the upper and lower arcades. CONCLUSION: Equine incisors
      are able to fully compensate occlusal wear for a limited period of time. However,
      after this ability ceases, it is expected that a diminished intraalveolar tooth
      length will cause massive changes in periodontal biomechanics. The time point of
      these morphodynamic and biomechanical changes (13 to 15 years post eruption)
      occurs in coincidence with the onset of a recently described destructive disease
      of equine incisor (equine odontoclastic tooth resorption and hypercementosis) in
      aged horses. However, further biomechanical, cell biological and microbiological
      investigations are needed to elucidate a correlation between age related changes
      of incisor morphology and this disease.

PMID- 24321366
TI  - Evaluation of ultrasonography for measuring solar soft tissue thickness as a
      predictor of sole ulcer formation in Holstein-Friesian dairy cows.
AB  - The aim of this research was to investigate the correlation between the thickness
      of solar soft tissue (SST; i.e. the corium and subcutaneous tissue) in early
      lactation and sole ulcer formation in late lactation. Fifty Holstein-Friesian
      cows were examined three times: (1) 30 days after calving (locomotion scoring,
      trimming, claw examination, measurement of SST); (2) 70 days after calving
      (locomotion scoring); and (3) 180 days after calving (locomotion scoring,
      trimming, claw examination). SST thickness was measured using an 8 MHz linear
      probe, at two points (SST1 below the apex of the pedal bone, and SST2 below the
      flexor tubercle). Mean values for SST1 and SST2 were 3.26 +/- 0.43 mm and 4.35 +/
      0.46 mm, respectively; the two measures were positively correlated (r=0.95,
      P<0.001). At 180 days after calving, a sole ulcer was diagnosed in 12/50 cows
      (24%). Cows with a thinner SST had a higher risk of developing sole ulcers than
      those with a thicker SST. The optimal cut-off values of SST1 and SST2 in
      predicting cows with sole ulcers (as calculated by ROC analysis) was ? 3 mm for
      SST1 and ? 3.9 mm for SST2. The relative risk of a sole ulcer developing, based
      on those cut-off values was 4.25 (95 CI, 1.77-24.88) for SST1 ? 3 mm and 3.63 (95
      CI, 1.18-10.8) for SST2 ? 3.9 mm.

PMID- 24321367
TI  - Evaluation of a technique to measure heart rate variability in anaesthetised
      cats.
AB  - Analysis of heart rate (HR) and heart rate variability (HRV) are powerful tools
      to investigate cardiac diseases, but current methods, including 24-h Holter
      monitoring, can be cumbersome and may be compromised by movement artefact. A
      commercially available data capture and analysis system was used in anaesthetised
      healthy cats to measure HR and HRV during pharmacological manipulation of HR.
      Seven healthy cats were subjected to a randomised crossover study design with a 7
      day washout period between two treatment groups, placebo and atenolol (1mg/kg,
      IV), with the efficacy of atenolol to inhibit beta1 adrenoreceptors challenged by
      epinephrine. Statistical significance for the epinephrine challenge was set at
      P<0.0027 (Holm-Bonferroni correction), whereas a level of significance of P<0.05
      was set for other variables. Analysis of the continuous electrocardiography (ECG)
      recordings showed that epinephrine challenge increased HR in the placebo group
      (P=0.0003) but not in the atenolol group. The change in HR was greater in the
      placebo group than in the atenolol group (P=0.0004). Therefore, compared to cats
      pre-treated with placebo, pre-treatment with atenolol significantly antagonised
      the tachycardia while not significantly affecting HRV. The increased HR in the
      placebo group following epinephrine challenge was consistent with a shift of the
      sympathovagal balance towards a predominantly sympathetic tone. However, the
      small (but not significant at the critical value) decrease in the normalised high
      frequency component (HFnorm) in both groups of cats suggested that epinephrine
      induced a parasympathetic withdrawal in addition to sympathetic enhancement
      (increased normalised low frequency component or LFnorm). In conclusion, this
      model is a highly sensitive and repeatable model to investigate HRV in
      anaesthetised cats that would be useful in the laboratory setting for short-term
      investigation of cardiovascular disease and subtle responses to pharmacological
      agents in this species.

PMID- 24321368
TI  - A comparison of 3-T magnetic resonance imaging and computed tomography
      arthrography to identify structural cartilage defects of the fetlock joint in the
      horse.
AB  - Articular cartilage defects are prevalent in metacarpo/metatarsophalangeal
      (MCP/MTP) joints of horses. The aim of this study was to determine and compare
      the sensitivity and specificity of 3-Tesla magnetic resonance imaging (3-T MRI)
      and computed tomography arthrography (CTA) to identify structural cartilage
      defects in the equine MCP/MTP joint. Forty distal cadaver limbs were imaged by
      CTA (after injection of contrast medium) and by 3-T MRI using specific sequences,
      namely, dual-echo in the steady-state (DESS), and sampling perfection with
      application-optimised contrast using different flip-angle evolutions (SPACE).
      Gross anatomy was used as the gold standard to evaluate sensitivity and
      specificity of both imaging techniques. CTA sensitivity and specificity were 0.82
      and 0.96, respectively, and were significantly higher than those of MRI (0.41 and
      0.93, respectively) in detecting overall cartilage defects (no defect vs.
      defect). The intra and inter-rater agreements were 0.96 and 0.92, respectively,
      and 0.82 and 0.88, respectively, for CT and MRI. The positive predictive value
      for MRI was low (0.57). CTA was considered a valuable tool for assessing
      cartilage defects in the MCP/MTP joint due to its short acquisition time, its
      specificity and sensitivity, and it was also more accurate than MRI. However, MRI
      permits assessment of soft tissues and subchondral bone and is a useful technique
      for joint evaluation, although clinicians should be aware of the limitations of
      this diagnostic technique, including reduced accuracy. 

PMID- 24321369
TI  - Differences in natural antibody titres comparing free-ranging guanacos (Lama
      guanicoe) and capybaras (Hydrochoerus hydrochaeris).
AB  - Natural antibodies are an important component of innate humoral immunity but have
      not been investigated to any great extent in wild mammals. In the current study,
      serum natural antibody titres were measured by hemagglutination assay for two
      South American herbivores, the guanaco (Lama guanicoe) and the capybara
      (Hydrochoerus hydrochaeris). Results indicated that capybaras had antibody titres
      on average more than four times higher than guanacos (median titres 1:256 and
      1:4, respectively), suggesting differences in investment in constitutive humoral
      immunity between the two species.

PMID- 24321370
TI  - Chemical analysis, inhibition of biofilm formation and biofilm eradication
      potential of Euphorbia hirta L. against clinical isolates and standard strains.
AB  - BACKGROUND: The frequent occurrences of antibiotic-resistant biofilm forming
      pathogens have become global issue since various measures that had been taken to
      curb the situation led to failure. Euphorbia hirta, is a well-known
      ethnomedicinal plant of Malaysia with diverse biological activities. This plant
      has been used widely in traditional medicine for the treatment of
      gastrointestinal, bronchial and respiratory ailments caused by infectious agents.
      METHODS: In the present study, chemical compositions of methanol extract of E.
      hirta L. aerial part was analyzed by gas chromatography and gas chromatography
      coupled to mass spectrometry. A relevant in vitro model was developed to assess
      the potency of the E. hirta extract to inhibit the bacterial biofilm formation as
      well as to eradicate the established biofilms. Besides biofilm, E. hirta extract
      was also evaluated for the inhibition efficacy on planktonic cells using
      tetrazolium microplate assay. For these purposes, a panel of clinically resistant
      pathogens and American type culture collection (ATCC) strains were used. RESULTS:
      The methanolic extract of aerial part of E. hirta was predominantly composed of
      terpenoid (60.5%) which is often regarded as an active entity accountable for the
      membrane destruction and biofilm cell detachment. The highest antibacterial
      effect of crude E. hirta extract was observed in the clinical isolates of
      Pseudomonas aeruginosa with minimum inhibitory concentration (MIC) value of 0.062
      mg/ml. The extract also displayed potent biofilm inhibition and eradication
      activity against P. aeruginosa with minimum biofilm inhibition concentration
      (MBIC) and minimum biofilm eradication concentration (MBEC) values of 0.25 mg/ml
      and 0.5 mg/ml, respectively. CONCLUSIONS: The crude methanol extract of E. hirta
      has proven to have interesting and potential anti-biofilm properties. The
      findings from this study will also help to establish a very promising anti
      infective phytotherapeutical to be exploited in the pharmaceutical industries.

PMID- 24321371
TI  - Histone deacetylases in cardiac fibrosis: current perspectives for therapy.
AB  - Cardiac fibrosis is an important pathological feature of cardiac remodeling in
      heart diseases. The molecular mechanisms of cardiac fibrosis are unknown. Histone
      deacetylases (HDACs) are enzymes that balance the acetylation activities of
      histone acetyltransferases on chromatin remodeling and play essential roles in
      regulating gene transcription. In recent years, the role of HDACs in cardiac
      fibrosis initiation and progression, as well as the therapeutic effects of HDAC
      inhibitors, has been well studied. Moreover, numerous studies indicated that HDAC
      activity is associated with the development and progression of cardiac fibrosis.
      In this review, the innovative aspects of HDACs are discussed, with respect to
      biogenesis, their role in cardiac fibrosis. Furthermore, the potential
      applications of HDAC inhibitors in the treatment of cardiac fibrosis associated
      with fibroblast activation and proliferation. 

PMID- 24321372
TI  - Implementation of a school-wide prevention programme-teachers' and headmasters'
      perceptions of organizational capacity.
AB  - This study focuses on schools' organizational capacity to implement a Swedish
      school-wide programme, Prevention in School (PS). It is based on semi-structured
      interviews with seven headmasters and 13 teachers from seven Swedish schools. The
      interviews were analyzed by the use of qualitative content analysis. The findings
      show that the adoption of a comprehensive intervention like PS challenges the
      school organization as the staff encountered a variety of organizational barriers
      when implementing the programme. Factors connected to lack of consensus,
      collaboration and insufficient programme management were the main barriers that
      were identified. Teachers wanted a more extensive support from their headmasters
      in terms of participation in different programme activities. It was emphasized
      that peer coaches need to be prepared for their task, although the headmasters
      found it difficult to be able to choose those teachers who they perceived as the
      most suitable. It is concluded that leadership, coaching and staff selection need
      particular attention when implementing a programme like PS, since those factors
      have been defined as important implementation drivers, both in this study and
      previously. 

PMID- 24321373
TI  - Biocompatibility and antifouling: is there really a link?

PMID- 24321374
TI  - Pharmacokinetics and safety of single doses of drisapersen in non-ambulant
      subjects with Duchenne muscular dystrophy: results of a double-blind randomized
      clinical trial.
AB  - Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder
      caused by the absence of dystrophin protein due to mutations of the dystrophin
      gene. Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to
      skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA.
      This study assessed safety, tolerability, and pharmacokinetics of drisapersen
      after a single subcutaneous administration in non-ambulatory subjects. Eligible
      subjects were non-ambulant boys aged ?9years, in wheelchairs for ?1 to ?4years,
      with a diagnosis of DMD resulting from a mutation correctable by drisapersen
      treatment. Four dose cohorts were planned (3, 6, 9 and 12mg/kg), but study
      objectives were met with the 9mg/kg dose. Less than proportional increase in
      exposure was demonstrated over the 3-9mg/kg dose range, though post hoc analysis
      showed dose proportionality was more feasible over the 3-6mg/kg range. Single
      doses of drisapersen at 3 and 6mg/kg did not result in significant safety or
      tolerability concerns; however, at the 9mg/kg dose, pyrexia and transient
      elevations in inflammatory parameters were seen. The maximum tolerated dose of
      6mg/kg drisapersen was identified for further characterization in multiple dose
      studies in the non-ambulant DMD population. 

PMID- 24321375
TI  - Perceptions of postnatal care: factors associated with primiparous mothers
      perceptions of postnatal communication and care.
AB  - BACKGROUND: The aim of this study was to determine whether personality and/or
      psychological functioning affect mothers' perceptions of postnatal communication
      and their level of satisfaction with their postnatal care. Mothers' perceptions
      of the communication with health professionals prenatally and during birth may be
      affected by their personality traits and psychological functioning and are linked
      to the level of satisfaction they have in their healthcare. Little is known about
      factors that are associated with perceptions of communication within postnatal
      care and the impact this may have on satisfaction with care. METHODS: A cross
      sectional survey recruited 71 first-time mothers, who had given birth vaginally
      in the U.K., within the previous 12 months. The questionnaire assessed
      personality traits using the Big 5 Mini Marker set, levels of anxiety and
      depression using HADS, perceptions of communication experienced with health
      professionals and overall levels of satisfaction with postnatal care via the
      Satisfaction with Care Scale. Covariates such as demographic factors were
      investigated. RESULTS: Higher ratings of communication were found to be directly
      correlated with higher satisfaction, as were the personality traits;
      agreeableness, conscientiousness and emotional stability. Depression
      significantly lowered participants' ratings of communication experienced with
      health visitors and total satisfaction. Mothers who breastfed had significantly
      lower communication and satisfaction ratings. Multiple regression analysis
      revealed communication ratings explained 71.8% of the variance in the level of
      satisfaction and none of the remaining predictors significantly directly affected
      satisfaction ratings. CONCLUSION: Future research should focus on the utility of
      these findings for improving care for primiparous mothers.

PMID- 24321376
TI  - Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression
      predicts mortality after septic shock.
AB  - INTRODUCTION: Septic syndromes remain the leading cause of mortality in intensive
      care units (ICU). Septic patients rapidly develop immune dysfunctions, the
      intensity and duration of which have been linked with deleterious outcomes.
      Decreased mRNA expressions of major histocompatibility complex (MHC) class II
      related genes have been reported after sepsis. We investigated whether their mRNA
      levels in whole blood could predict mortality in septic shock patients. METHODS:
      A total of 93 septic shock patients were included. On the third day after shock,
      the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB,
      HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR
      (mHLA-DR) by flow cytometry. RESULTS: A significant correlation was found among
      MHC class II related gene expressions. Among mRNA markers, the best prognostic
      value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this
      parameter, the area under the receiver operating characteristic curve (AUC) was
      calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as
      well as the optimal cut-off value. After stratification based on this threshold,
      survival curves showed that a decreased CD74 mRNA level was associated with
      increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio =
      3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant
      after multivariate logistic regression analysis including usual clinical
      confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2
      to 9.8). CONCLUSION: Decreased CD74 mRNA expression significantly predicts 28-day
      mortality after septic shock. After validation in a larger multicentric study,
      this biomarker could become a robust predictor of death in septic patients.

PMID- 24321377
TI  - Twisting and ignoring facts on hydroxyethyl starch is not very helpful.
AB  - Large randomized trials on critically ill patients have related the use of
      hydroxyethyl starch (HES) to negative outcomes. In a recent comment we explained
      in detail why, from our point of view, transferring the results of VISEP, 6S and
      CHEST into daily ICU practice is as difficult as their extrapolation to
      perioperative treatment. Haase, Muller and Perner lately challenged this
      analysis. However, after having carefully read their letter to the editor we are
      happy to demonstrate that all points we made were absolutely correct. We agree
      with Haase et al. that a debate on HES safety is important, but has to be based
      on facts. The difference might be that we like to thoroughly discuss all of them,
      including the main one: VISEP, 6S and CHEST do not capture the initial
      stabilization of their hemodynamically instable patients. The vast majority,
      including those patients later assigned to the "crystalloid" groups, had been
      stabilized with colloids before study onset. This is not a big problem, but has
      to be discussed carefully and honestly to prevent the data from being
      misinterpreted by users and official authorities. 

PMID- 24321378
TI  - Adipose tissue, diet and aging.
AB  - Age related increase in body fat mass, visceral adipose tissue (AT), and ectopic
      fat deposition are strongly related to worse health conditions in the elderly.
      Moreover, with aging higher inflammation in adipose tissue may be observed and
      may contribute to inflammaging. Aging may significantly affect AT function by
      modifying the profile of adipokines produced by adipose cells, reducing
      preadipocytes number and their function and increasing AT macrophages
      infiltration. The initiating events of the inflammatory cascade promoting a
      greater AT inflammatory profile are not completely understood. Nutrients may
      determine changes in the amount of body fat, in its distribution as well as in AT
      function with some nutrients showing a pro-inflammatory effect on AT. Evidences
      are sparse and quite controversial with only a few studies performed in older
      subjects. Different dietary patterns are the result of the complex interaction of
      foods and nutrients, thus more studies are needed to evaluate the association
      between dietary patterns and changes in adipose tissue structure, distribution
      and function in the elderly. 

PMID- 24321379
TI  - Tracheal compression secondary to posterior sternoclavicular dislocation.

PMID- 24321380
TI  - Comparison of intermittent positive pressure breathing and temporary positive
      expiratory pressure in patients with severe chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Results supporting the use and the effectiveness of positive
      expiratory, pressure devices in chronic obstructive pulmonary disease (COPD)
      patients are still controversial, We have tested the hypothesis that adding TPEP
      or IPPB to standard pharmacological therapy may provide additional clinical
      benefit over, pharmacological therapy only in patients with severe COPD. METHODS:
      Fourty-five patients were randomized in three groups: a group was treated; with
      IPPB,a group was treated with TPEP and a group with pharmacological; therapy
      alone (control group). Primary outcome measures included the measurement of scale
      or, questionnaire concerning dyspnea (MRC scale),dyspnea,cough, and, sputum
      (BCSS) and quality of life (COPD assessment test) (CAT). Secondary, outcome
      measures were respiratory function testing,arterial blood gas,analysis,and
      hematological examinations. RESULTS: Both patients in the IPPB group and in the
      TPEP group showed a significant, improvement in two of three tests (MRC,CAT)
      compared to the control, group.However,in the group comparison analysis for, the
      same variables between IPPB group and TPEP group we observed a, significant
      improvement in the IPPB group (P<=.05 for MRC and P<=.01 for, CAT). The
      difference of action of the two techniques are evident in the results of,
      pulmonary function testing: IPPB increases FVC, FEV1, and MIP; this reflects, its
      capacity to increase lung volume. Also TPEP increases FVC and FEV1 (less, than
      IPPB), but increases MEP, while decreasing total lung capacity and, residual
      volume. CONCLUSIONS: The two techniques (IPPB and TPEP) improves significantly
      dyspnea; quality of; life tools and lung function in patients with severe COPD.
      IPPB demonstrated a greater effectiveness to improve dyspnea and quality of life
      tools (MRC, CAT) than TPEP.

PMID- 24321381
TI  - Oncolytic vaccinia virus in combination with radiation shows synergistic
      antitumor efficacy in pancreatic cancer.
AB  - Combining oncolytic viruses with conventional therapy such as radiation is an
      innovative option for pancreatic cancer. We demonstrated that combination of GLV
      1h151 and radiation yielded a synergistic cytotoxic effect, with the greatest
      effect achieved in the AsPC-1cell line. Combination treatment significantly
      increased apoptosis compared with either single treatment or the control group.
      In mice bearing human pancreatic tumor xenografts, combination treatment resulted
      in significantly enhanced inhibition of tumor growth. No evidence of toxicity was
      observed in mice. These results indicate that the combination of GLV-1h151 and
      radiation has great potential for translation into clinic practice.

PMID- 24321382
TI  - In-situ observation of equilibrium transitions in Ni films; agglomeration and
      impurity effects.
AB  - Dewetting of ultra-thin Ni films deposited on SiO2 layers was observed, in cross
      section, by in situ scanning transmission electron microscopy. Holes were
      observed to nucleate by voids which formed at the Ni/SiO2 interface rather than
      at triple junctions at the free surface of the Ni film. Ni islands were observed
      to retract, in attempt to reach equilibrium on the SiO2 layer. SiO2 layers with
      120 nm thickness were found to limit in situ heating experiments due to poor
      thermal conductivity of SiO2. The formation of graphite was observed during the
      agglomeration of ultra-thin Ni films. Graphite was observed to wet both the free
      surface and the Ni/SiO2 interface of the Ni islands. Cr forms surface oxide
      layers on the free surface of the SiO2 layer and the Ni islands. Cr does not
      prevent the dewetting of Ni, however it will likely alter the equilibrium shape
      of the Ni islands.

PMID- 24321383
TI  - Comparison of the performance of two spontaneous sedimentation techniques for the
      diagnosis of human intestinal parasites in the absence of a gold standard.
AB  - Performance evaluation of diagnostic tests is critical in the search for accurate
      diagnoses. A gold standard test is usually absent in parasitology, thus rendering
      satisfactory assessment of diagnostic accuracy difficult. Moreover, reliability
      (assessed by the study of repeatability) is a rarely studied characteristic of
      diagnostic tests. This study compared and evaluated the performance
      (repeatability, concordance and accuracy) of the spontaneous sedimentation
      technique (SST) and the Paratest for the diagnosis of Giardia lamblia, Entamoeba
      histolytica complex, Blastocystis spp., Ascaris lumbricoides, hookworm, Trichuris
      trichiura and Calodium hepaticum. Fecal samples of 143 individuals were separated
      into three replicates for each test. Concordance and homogeneity of the results
      between replicates of each test and between tests were evaluated. Proportions of
      positives, sensitivity and specificity were estimated using a Bayesian Latent
      Class Model. High repeatability of both tests was found for the detection of
      intestinal parasites, except for Blastocystis spp. and hookworm. Concordance
      between tests was generally high (concordance correlation coefficient, 0.72
      0.88), except for Blastocystis spp., hookworm and T. trichiura. The Paratest
      detected more cases of Blastocystis spp. and fewer of hookworm than the SST. The
      tests were quite discordant in the detection of T. trichiura. A low sensitivity
      (39.4-49.2% for SST, 35.8-53.8% for Paratest) and a high specificity (93.2-97.2%)
      were found for both tests. The Paratest presented a slightly higher sensitivity
      for the diagnosis of Blastocystis spp. (53.8%), and SST did so for hookworm
      (49.2%). This is the first study on repeatability and accuracy (using a Bayesian
      approach) of two spontaneous sedimentation techniques. These results suggest
      underdiagnosis of little dense parasitic forms due to technical limitations in
      both tests. We conclude that the combined study of repeatability, concordance and
      accuracy is a key strategy for better evaluation of the performance of tests and
      is also useful for the identification of technical limitations. 

PMID- 24321384
TI  - Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through
      interaction with exon 8.
AB  - Alternative splicing plays an important role in gene expression by producing
      different proteins from a gene. Caspase-2 pre-mRNA produces anti-apoptotic Casp
      2S and pro-apoptotic Casp-2L proteins through exon 9 inclusion or skipping.
      However, the molecular mechanisms of exon 9 splicing are not well understood.
      Here we show that knockdown of SRSF3 (also known as SRp20) with siRNA induced
      significant increase of endogenous exon 9 inclusion. In addition, overexpression
      of SRSF3 promoted exon 9 skipping. Thus we conclude that SRSF3 promotes exon 9
      skipping. In order to understand the functional target of SRSF3 on caspase-2 pre
      mRNA, we performed substitution and deletion mutagenesis on the potential SRSF3
      binding sites that were predicted from previous reports. We demonstrate that
      substitution mutagenesis of the potential SRSF3 binding site on exon 8 severely
      disrupted the effects of SRSF3 on exon 9 skipping. Furthermore, with the approach
      of RNA pulldown and immunoblotting analysis we show that SRSF3 interacts with the
      potential SRSF3 binding RNA sequence on exon 8 but not with the mutant RNA
      sequence. In addition, we show that a deletion of 26nt RNA from 5' end of exon 8,
      a 33nt RNA from 3' end of exon 10 and a 2225nt RNA from intron 9 did not
      compromise the function of SRSF3 on exon 9 splicing. Therefore we conclude that
      SRSF3 promotes exon 9 skipping of caspase-2 pre-mRNA by interacting with exon 8.
      Our results reveal a novel mechanism of caspase-2 pre-mRNA splicing. 

PMID- 24321385
TI  - Cohesin and CTCF differentially regulate spatiotemporal runx1 expression during
      zebrafish development.
AB  - Runx1 is a transcription factor essential for definitive hematopoiesis. In all
      vertebrates, the Runx1 gene is transcribed from two promoters: a proximal
      promoter (P2), and a distal promoter (P1). We previously found that runx1
      expression in a specific hematopoietic cell population in zebrafish embryos
      depends on cohesin. Here we show that zebrafish runx1 is directly bound by
      cohesin and CCCTC binding factor (CTCF) at the P1 and P2 promoters, and within
      the intron between P1 and P2. Cohesin initiates expression of runx1 in the
      posterior lateral mesoderm and influences promoter use, while CTCF represses its
      expression in the newly emerging cells of the tail bud. The intronic binding
      sites for cohesin and CTCF coincide with histone modifications that confer
      enhancer-like properties, and two of the cohesin/CTCF sites behaved as insulators
      in an in vivo assay. The identified cohesin and CTCF binding sites are likely to
      be cis-regulatory elements (CREs) for runx1 since they also recruit RNA
      polymerase II (RNAPII). CTCF depletion excluded RNAPII from two intronic CREs but
      not the promoters of runx1. We propose that cohesin and CTCF have distinct
      functions in the regulation of runx1 during zebrafish embryogenesis, and that
      these regulatory functions are likely to involve runx1 intronic CREs. Cohesin
      (but not CTCF) depletion enhanced RUNX1 expression in a human leukemia cell line,
      suggesting conservation of RUNX1 regulation through evolution. 

PMID- 24321386
TI  - Transcriptional regulation of human ferredoxin reductase through an intronic
      enhancer in steroidogenic cells.
AB  - Ferredoxin reductase (FDXR, also known as adrenodoxin reductase) is a
      mitochondrial flavoprotein that transfers electrons from NADPH to mitochondrial
      cytochrome P450 enzymes, mediating the function of an iron-sulfur cluster
      protein, ferredoxin. FDXR functions in various metabolic processes including
      steroidogenesis. It is well known that multiple steroidogenic enzymes are
      regulated by a transcription factor steroidogenic factor-1 (SF-1, also known as
      Ad4BP). Previously, we have shown that SF-1 transduction causes human mesenchymal
      stem cell differentiation into steroidogenic cells. Genome-wide analysis of
      differentiated cells, using a combination of DNA microarray and promoter tiling
      array analyses, showed that FDXR is a novel SF-1 target gene. In this study, the
      transcriptional regulatory mechanism of FDXR was examined in steroidogenic cells.
      A chromatin immunoprecipitation assay revealed that a novel SF-1 binding region
      was located within intron 2 of the human FDXR gene. Luciferase reporter assays
      showed that FDXR transcription was activated through the novel SF-1 binding site
      within intron 2. Endogenous SF-1 knockdown in human adrenocortical H295R and KGN
      cells decreased FDXR expression. In H295R cells, strong binding of two histone
      markers of active enhancers, histones H3K27ac and H3K4me2, were detected near the
      SF-1 binding site within intron 2. Furthermore, the binding of these histone
      markers was decreased concurrent with SF-1 knockdown in H295R cells. These
      results indicated that abundant FDXR expression in these steroidogenic cells was
      maintained through SF-1 binding to the intronic enhancer of the FDXR gene. 

PMID- 24321387
TI  - Analysis of drugs of abuse in wastewater from two Canadian cities.
AB  - Several drugs of abuse, including amphetamines, cocaine and its metabolite,
      benzoylecgonine and several opioid prescription drugs were detected in wastewater
      from two Canadian cities, a small community (75,000 population) and a large urban
      center (1.6 million population). The objective of this study was to evaluate
      community use of these drugs in two cities with large differences in population
      size and demographics. In addition, we evaluated the use of the Polar Organic
      Chemical Integrative Sampler (POCIS) as a monitoring tool for drugs of abuse.
      Heroin was not detected at either location, probably because this illicit drug is
      metabolized to morphine prior to excretion. Acetylcodeine and acetylmorphine were
      also not detected. Estimates of community consumption from wastewater analysis
      indicated that the most widely used drug was cocaine at a median level of
      consumption in the larger city of approximately 38 doses per day per 1000 people.
      Consumption of the substituted amphetamine, ephedrine, as well as methamphetamine
      was also higher in the larger city, at 21 and 1.8 doses per day per 1000 people,
      respectively. Use of amphetamine, MDMA and tramadol were similar in both centers,
      but use of oxycodone was greater in the smaller city. Use of MDMA (ecstasy)
      peaked on weekends. Ketamine was detected in wastewater from the larger city; the
      first report of abuse of this veterinary anesthetic in a North American city.
      POCIS sampling rates were determined for the first time for 7 of the target
      compounds. Comparing the time weighted average concentrations estimated from
      POCIS data to the concentrations obtained from 24-h composite samples, the data
      were generally comparable, except for some compounds which were not detected in
      POCIS deployed in the untreated wastewater, probably because of biofouling or
      accumulation of debris on the cages containing the POCIS. This study indicates
      that the size and demographics of population centers can influence the patterns
      of abuse of drugs.

PMID- 24321388
TI  - Mitigating arsenic crisis in the developing world: role of robust, reusable and
      selective hybrid anion exchanger (HAIX).
AB  - In trying to address the public health crisis from the lack of potable water,
      millions of tube wells have been installed across the world. From these tube
      wells, natural groundwater contamination from arsenic regularly puts at risk the
      health of over 100 million people in South and Southeast Asia. Although there
      have been many research projects, awards and publications, appropriate treatment
      technology has not been matched to ground level realities and water solutions
      have not scaled to reach millions of people. For thousands of people from Nepal
      to India to Cambodia, hybrid anion exchange (HAIX) resins have provided arsenic
      safe water for up to nine years. Synthesis of HAIX resins has been commercialized
      and they are now available globally. Robust, reusable and arsenic-selective, HAIX
      has been in operation in rural communities over numerous cycles of exhaustion
      regeneration. All necessary testing and system maintenance is organized by
      community-level water staff. Removed arsenic is safely stored in a scientifically
      and environmentally appropriate manner to prevent future hazards to animals or
      people. Recent installations have shown the profitability of HAIX-based arsenic
      treatment, with capital payback periods of only two years in ideal locations.
      With an appropriate implementation model, HAIX-based treatment can rapidly scale
      and provide arsenic-safe water to at-risk populations.

PMID- 24321389
TI  - [Domiciliary parenteral antibiotic therapy: a prospective analysis of the last 12
      years].
AB  - OBJETIVES: Parenteral antibiotic treatment has been classically developed in
      hospitals and is considered as a hospital procedure. The development of Hospital
      at Home Units (HHU) has led to an increase in outpatient parenteral antibiotic
      therapy (OPAT) in paediatrics patients. The objective of this study is to
      describe our experience, as an HHU integrated within a Paediatric Department, in
      home antimicrobial therapy over a period of 12 years. PATIENTS AND METHODS: This
      prospective and descriptive study included every patient with a disease requiring
      parenteral antimicrobial therapy who was admitted to our HHU from January 2000 to
      December 2012. RESULTS: During the study there were 163 cases on OPAT. The mean
      age of the patients was 11.1 years, and the sample group was comprised of 33
      males and 22 feamales. The main sources of the treated infections were
      respiratory tract (76%), catheter-related bloodstream (9.2%), and urinary tract
      infections (5.5%). Amikacin was the most widely used antibiotic. Almost all
      treatments (96.6%) were via an intravenous route. Catheter-associated
      complications were more common than drug-associated complications. Successful at
      home treatment was observed in 90.2% of cases. CONCLUSIONS: OPAT is a good and
      safe alternative in many paediatric diseases.

PMID- 24321390
TI  - Gastrointestinal Endoscopy Competency Assessment Tool: development of a procedure
      specific assessment tool for colonoscopy.
AB  - BACKGROUND: Ensuring competence remains a seminal objective of endoscopy training
      programs, professional organizations, and accreditation bodies; however, no
      widely accepted measure of endoscopic competence currently exists. OBJECTIVE: By
      using Delphi methodology, we aimed to develop and establish the content validity
      of the Gastrointestinal Endoscopy Competency Assessment Tool for colonoscopy.
      DESIGN: An international panel of endoscopy experts rated potential checklist and
      global rating items for their importance as indicators of the competence of
      trainees learning to perform colonoscopy. After each round, responses were
      analyzed and sent back to the experts for further ratings until consensus was
      reached. MAIN OUTCOME MEASUREMENTS: Consensus was defined a priori as >=80% of
      experts, in a given round, scoring >=4 of 5 on all remaining items. RESULTS:
      Fifty-five experts agreed to be part of the Delphi panel: 43 gastroenterologists,
      10 surgeons, and 2 endoscopy managers. Seventy-three checklist and 34 global
      rating items were generated through a systematic literature review and survey of
      committee members. An additional 2 checklist and 4 global rating items were added
      by Delphi panelists. Five rounds of surveys were completed before consensus was
      achieved, with response rates ranging from 67% to 100%. Seven global ratings and
      19 checklist items reached consensus as good indicators of the competence of
      clinicians performing colonoscopy. LIMITATIONS: Further validation required.
      CONCLUSION: Delphi methodology allowed for the rigorous development and content
      validation of a new measure of endoscopic competence, reflective of practice
      across institutions. Although further evaluation is required, it is a promising
      step toward the objective assessment of competency for use in colonoscopy
      training, practice, and research.

PMID- 24321391
TI  - Using efficiency analysis and targeted intervention to improve operational
      performance and achieve cost savings in the endoscopy center.
AB  - BACKGROUND: With an increasing demand for endoscopy services, there is a greater
      need for efficiency within the endoscopy center. A validated methodology is
      important for evaluating efficiency in the endoscopy unit. OBJECTIVE: To use the
      principles of operations management to establish a validated methodology for
      evaluating and enhancing operational performance in the endoscopy center. DESIGN:
      Biphasic prospective study with pre-intervention and post-intervention efficiency
      data and analysis. SETTING: Tertiary-care referral teaching hospital. PATIENTS:
      Scheduled outpatients undergoing endoscopy. INTERVENTION: Determination of the
      rate-limiting step, or bottleneck, of the endoscopy unit and reducing
      inefficiencies. MAIN OUTCOME MEASUREMENTS: Staffing costs and a novel performance
      metric, True Completion Time (TCT). RESULTS: Data were prospectively recorded for
      2248 patients undergoing a total of 2713 procedures (phase I: 255 EGD, 305
      colonoscopy, 91 EGD/colonoscopy, 375 EUS, 44 ERCP, 75 EUS/ERCP; phase II: 243
      EGD, 328 colonoscopy, 99 EGD/colonoscopy, 335 EUS, 38 ERCP, 109 EUS/ERCP). The
      bottleneck of the operation was identified as the 10-bed communal pre
      procedure/recovery room. On-time procedure starts increased by 51% (P < .001),
      and TCT was reduced by 12.2% (P < .001) across all cases studied. Overtime and
      per diem nursing costs were reduced by 30%, whereas full-time employee staff was
      reduced by 0.85. Annual cost savings were calculated as $312,618 or 11.02% of
      total operating expenses. LIMITATIONS: This study is not directly tied to quality
      outcomes, and inpatient procedures transported to the endoscopy unit were not
      directly studied. CONCLUSION: Room turnover time and room-to-endoscopist ratio
      are not necessarily the driving parameters behind endoscopy unit efficiency. A
      focus on developing a methodology for identifying factors constraining
      operational efficiency can improve performance and reduce costs in the endoscopy
      center.

PMID- 24321392
TI  - Risk factors for locoregional recurrence in patients with resected N1 non-small
      cell lung cancer: a retrospective study to identify patterns of failure and
      implications for adjuvant radiotherapy.
AB  - BACKGROUND: Meta-analysis of randomized trials has shown that postoperative
      radiotherapy (PORT) had a detrimental effect on overall survival (OS) in patients
      with resected N1 non-small cell lung cancer (NSCLC). Conversely, the locoregional
      recurrence (LR) rate is reported to be high without adjuvant PORT in these
      patients. We have evaluated the pattern of failure, actuarial risk and risk
      factors for LR in order to identify the subset of N1 NSCLC patients with the
      highest risk of LR. These patients could potentially benefit from PORT. METHODS:
      We conducted a retrospective study on 199 patients with pathologically confirmed
      T1-3N1M0 NSCLC who underwent surgery. None of the patients had positive surgical
      margins or received preoperative therapy or PORT. The median follow-up was 53.8
      months. Complete mediastinal lymph node (MLN) dissection and examination was
      defined as >=3 dissected and examined MLN stations; incomplete MLN dissection or
      examination (IMD) was defined as <3 dissected or examined MLN stations. The
      primary end point of this study was freedom from LR (FFLR). Differences between
      patient groups were compared and risk factors for LR were identified by
      univariate and multivariate analyses. RESULTS: LR was identified in 41 (20.6%)
      patients, distant metastasis (DM) was identified in 79 (39.7%) patients and
      concurrent LR and DM was identified in 25 (12.6%) patients. The 3- and 5-year OS
      rates in patients with resected N1 NSCLC were 78.4% and 65.6%, respectively. The
      corresponding FFLR rates were 80.8% and 77.3%, respectively. Univariate analyses
      identified that nonsmokers, <=23 dissected lymph nodes, visceral pleural invasion
      and lymph node ratio >10% were significantly associated with lower FFLR rates (P
      < 0.05). Multivariate analyses further confirmed positive lymph nodes at station
      10 and IMD as risk factors for LR (P < 0.05). The 5-year LR rate was highest in
      patients with both these risk factors (48%). CONCLUSIONS: The incidence of LR in
      patients with surgically resected T1-3N1M0 NSCLC is high. Patients with IMD and
      positive lymph nodes at station 10 have the highest risk of LR, and may therefore
      benefit from adjuvant PORT. Further investigations of PORT in this subset of
      patients are warranted.

PMID- 24321393
TI  - Comparison of the skin penetration of Garcinia mangostana extract in particulate
      and non-particulate form.
AB  - The aim of the present study was to solve the water insolubility limitation of
      the medically and cosmetically interesting substance Garcinia mangostana Linn
      (GML) extract by encapsulation, and to evaluate and investigate the penetration
      efficacy of free and encapsulated GML in two different vehicles (water and cream)
      in porcine ear skin. The follicular penetration depth was determined in 50 hair
      follicles for each of the four formulations by means of fluorescence microscopy.
      Tape stripping was used to compare the distribution properties of GML with all
      formulations on the stratum corneum. The results showed that encapsulated and
      free GML in the cream base penetrated deeper into hair follicles than if applied
      in an aqueous base. In addition, encapsulated GML could be distributed more
      homogeneously on the stratum corneum than the free GML. In conclusion, it was
      found that encapsulated GML in a cream base had the most effective penetration
      level in porcine ear skin. 

PMID- 24321395
TI  - Correction: Glycemic control and diabetes management in hospitalized patients in
      Brazil.

PMID- 24321394
TI  - Meta-analysis of the efficacy of pancreatoduodenectomy with extended
      lymphadenectomy in the treatment of pancreatic cancer.
AB  - BACKGROUND: The purpose of this meta-analysis is to compare the efficacy of
      pancreatoduodenectomy (PD) with extended lymphadenectomy (PD/ELND) versus
      standard PD in the treatment of pancreatic cancer, with the hope of providing
      evidence for clinical practice. METHODS: The retrieval of relevant literature
      published before September 2012 was carried out on PubMed, Medline, Embase, and
      Cochrane Central Register of Controlled Trials (CENTRAL) by computer. Information
      was extracted according to Cochrane systematic review methods, and analyzed using
      software Stata 11.0. RESULTS: Five prospective randomized controlled trials
      (RCTs) were included in this meta-analysis of 555 cases (278 in the PD/ELND group
      and 277 in the standard PD group). The PD/ELND group showed a significantly lower
      3-year survival rate (relative risk (RR) = 1.46, 95% confidence interval (CI)
      1.03 to approximately 2.06, P = 0.034), prolonged operative time (weighted mean
      difference WMD = -1.03, 95% CI -1.96 to approximately -0.10, P = 0.029) and
      higher incidence of postoperative complications (RR = 0.56, 95% CI 0.42 to
      approximately 0.77, P = 0.000) by comparing with standard PD group. Besides, no
      significant difference was observed in the 1-year survival rate (RR = 0.87, 95%
      CI 0.60 to approximately 1.25, P = 0.69), 5-year survival rate (RR = 1.04, 95% CI
      0.68 to approximately 1.58, P = 0.854), postoperative mortality (RR = 1.14, 95%
      CI 0.43 to approximately 3.00, P = 0.789), length of stay (WMD = -0.32, 95% CI 
      2.57 to approximately 1.94 , P = 0.784) and the amount of blood transfusions (WMD
      = -0.14, 95% CI -0.36 to approximately 0.08, P = 0.213). CONCLUSIONS: PD/ELND
      does not have an advantage over standard PD in the survival rate for patients
      with pancreatic cancer, but does increase operative time and incidences of
      postoperative complications.

PMID- 24321396
TI  - Human complement C3 deficiency: Th1 induction requires T cell-derived complement
      C3a and CD46 activation.
AB  - Human T helper type 1 (Th1) responses are essential in defense. Although T cell
      receptor (TCR) and co-stimulator engagement are indispensable for T cell
      activation, stimulation of additional receptor pathways are also necessary for
      effector induction. For example, engagement of the complement regulator CD46 by
      its ligand C3b generated upon TCR activation is required for IFN-gamma production
      as CD46-deficient patients lack Th1 responses. Utilizing T cells from two C3
      deficient patients we demonstrate here that normal Th1 responses also depend on
      signals mediated by the anaphylatoxin C3a receptor (C3aR). Importantly, and like
      in CD46-deficient patients, whilst Th1 induction are impaired in C3-deficient
      patients in vitro, their Th2 responses are unaffected. Furthermore, C3-deficient
      CD4(+) T cells present with reduced expression of CD25 and CD122, further
      substantiating the growing notion that complement fragments regulate interleukin
      2 receptor (IL-2R) assembly and that disturbance of complement-guided IL-2R
      assembly contributes to aberrant Th1 effector responses. Lastly, sustained
      intrinsic production of complement fragments may participate in the Th1
      contraction phase as both C3a and CD46 engagement regulate IL-10 co-expression in
      Th1 cells. These data suggest that C3aR and CD46 activation via intrinsic
      generation of their respective ligands is an integral part of human Th1 (but not
      Th2) immunity. 

PMID- 24321397
TI  - Assessment of naturally occurring covalent and total dimer levels in human IgG1
      and IgG2.
AB  - Antibody dimers, two self-associated monomers, have been detected on both
      recombinantly expressed and endogenous human IgG proteins. Nearly 10 years ago,
      Yoo et al. (2003) described low levels of IgG2 covalent dimer, in human serum,
      but did not quantify the levels. Here we quantify the total and covalent dimer
      levels of IgG2 and IgG1 in human blood, and study the origin of covalent dimer
      formation. Low levels (<1%) of total IgG1 and IgG2 dimers were measured in
      freshly prepared human plasma. Both IgG1 and IgG2 covalent dimers were also found
      in plasma. Whereas IgG1 covalent dimer levels were significantly reduced by steps
      intended to eliminate artifacts during sample preparation, IgG2 covalent dimer
      levels remain stable in such conditions. About 0.4% of IgG2 in plasma was in a
      covalent dimer form, yet very little (<0.03%) of IgG1 covalent dimer could be
      considered naturally occurring. IgG2 dimer also formed in vitro under conditions
      designed to mimic those in blood, suggesting that formation occurs in vivo during
      circulation. Thus, small amounts of covalent IgG2 dimer do appear to form
      naturally. 

PMID- 24321398
TI  - Ovarian cancer stem cells: are they real and why are they important?
AB  - The cancer stem cell hypothesis has been put forward as a paradigm to describe
      varying levels of aggressiveness in heterogeneous tumors. Specifically, many
      subpopulations have been clearly demonstrated to possess increased tumorigenicity
      in mice, broad differentiating capacity, and resistance to therapy. However, the
      extent to which these experimental findings are potentially clinically
      significant is still not clear. This review will describe the principles of this
      emerging hypothesis, ways in which it may be appropriate in ovarian cancer based
      on the clinical course of the disease, and how we might exploit it to improve
      outcomes in ovarian cancer patients. 

PMID- 24321399
TI  - A distinctive ovarian cancer molecular subgroup characterized by poor prognosis
      and somatic focal copy number amplifications at chromosome 19.
AB  - OBJECTIVE: High-grade serous ovarian cancer (HGS-OvCa), the most common
      epithelial ovarian cancer, is very complex and heterogeneous at the molecular
      level. The identification of intrinsic HGS-OvCa subgroups characterized by
      specific molecular alterations and aggressive behavior could improve patient
      treatment. METHODS: High-resolution copy number data for 560 HGS-OvCa patients
      and gene expression data obtained from the TCGA database were analyzed to
      identify distinct molecular subgroups based on significant focal somatic copy
      number alterations (SCNAs). RESULTS: Using unsupervised consensus clustering, a
      subgroup accounting for 26.8% of the patients (150/560 patients) characterized by
      focal somatic copy number amplification at chromosome 19 was identified. The
      subgroup was independently associated by multivariate Cox regression analysis
      with poor overall (HR, 1.61; P = 0.001) and progression-free survival (HR, 1.36;
      P = 0.036). The specific focal SCNA locations were 19p13.2, 19p13.12, 19p13.11,
      19q12, 19q13.12, and 19q13.2. The differential gene expression signature of the
      subgroup compared with that of the remaining patients also suggested that
      chromosome 19 was the mainly amplified region. The clinical significances of
      subgroup 2 were validated in independent data sets using the gene expression
      signature characteristics. In addition, the subgroup had a tendency toward mutual
      exclusivity with patients with BRCA1/2 mutations. The most significantly altered
      pathway of the subgroup was the cyclin and cell cycle regulation pathway.
      CONCLUSION: A unique molecular subgroup associated with poor survival was
      identified based on focal SCNAs and could aid the further molecular
      classification of ovarian cancers.

PMID- 24321400
TI  - Does neoadjuvant chemotherapy impair long-term survival for ovarian cancer
      patients? A nationwide Danish study.
AB  - OBJECTIVE: In Denmark, the proportion of women with ovarian cancer treated with
      neoadjuvant chemotherapy (NACT) has increased, and the use of NACT varies among
      center hospitals. We aimed to evaluate the impact of first-line treatment on
      surgical outcome and median overall survival (MOS). METHODS: All patients treated
      in Danish referral centers with stage IIIC or IV epithelial ovarian cancer from
      January 2005 to October 2011 were included. Data were obtained from the Danish
      Gynecological Cancer Database, the Danish National Patient Register and medical
      records. RESULTS: Of the 1677 eligible patients, 990 (59%) were treated with
      primary debulking surgery (PDS), 515 (31%) with NACT, and 172 (10%) received
      palliative treatment. Of the patients referred to NACT, 335 (65%) received
      interval debulking surgery (IDS). Patients treated with NACT-IDS had shorter
      operation times, less blood loss, less extensive surgery, fewer intraoperative
      complications and a lower frequency of residual tumor (p < 0.05 for all). No
      difference in MOS was found between patients treated with PDS (31.9 months) and
      patients treated with NACT-IDS (29.4 months), p = 0.099. Patients without
      residual tumor after surgery had better MOS when treated with PDS compared with
      NACT-IDS (55.5 and 36.7 months, respectively, p = 0.002). In a multivariate
      analysis, NACT-IDS was associated with increased risk of death after two years of
      follow-up (HR: 1.81; CI: 1.39-2.35). CONCLUSIONS: No difference in MOS was
      observed between PDS and NACT-IDS. However, patients without residual tumor had
      superior MOS when treated with PDS, and NACT-IDS could be associated with
      increased risk of death after two years of follow-up.

PMID- 24321401
TI  - The novel application of Benford's second order analysis for monitoring radiation
      output in interventional radiology.
AB  - Benford's law is an empirical observation which predicts the expected frequency
      of digits in naturally occurring datasets spanning multiple orders of magnitude,
      with the law having been most successfully applied as an audit tool in
      accountancy. This study investigated the sensitivity of the technique in
      identifying system output changes using simulated changes in interventional
      radiology Dose-Area-Product (DAP) data, with any deviations from Benford's
      distribution identified using z-statistics. The radiation output for
      interventional radiology X-ray equipment is monitored annually during quality
      control testing; however, for a considerable portion of the year an increased
      output of the system, potentially caused by engineering adjustments or
      spontaneous system faults may go unnoticed, leading to a potential increase in
      the radiation dose to patients. In normal operation recorded examination
      radiation outputs vary over multiple orders of magnitude rendering the
      application of normal statistics ineffective for detecting systematic changes in
      the output. In this work, the annual DAP datasets complied with Benford's first
      order law for first, second and combinations of the first and second digits.
      Further, a continuous 'rolling' second order technique was devised for trending
      simulated changes over shorter timescales. This distribution analysis, the first
      employment of the method for radiation output trending, detected significant
      changes simulated on the original data, proving the technique useful in this
      case. The potential is demonstrated for implementation of this novel analysis for
      monitoring and identifying change in suitable datasets for the purpose of system
      process control. 

PMID- 24321402
TI  - A randomized controlled trial of pre-conception treatment for periodontal disease
      to improve periodontal status during pregnancy and birth outcomes.
AB  - BACKGROUND: Evidence has suggested that periodontal disease is associated with an
      increased risk of various adverse pregnancy and birth outcomes. However, several
      large clinical randomized controlled trials failed to demonstrate periodontal
      therapy during pregnancy reduced the incidence of adverse pregnancy and birth
      outcomes. It has been suggested that the pre-conception period may be an optimal
      period for periodontal disease treatment rather than during pregnancy. To date,
      no randomized controlled trial (RCT) has examined if treating periodontal disease
      before pregnancy reduces adverse birth outcomes. This study aims to examine if
      the pre-conception treatment of periodontal disease will lead to improved
      periodontal status during late pregnancy and subsequent birth outcomes.
      METHODS/DESIGN: A sample of 470 (235 in each arm of the study) pre-conception
      women who plan to conceive within one year and with periodontal disease will be
      recruited for the study. All participants will be randomly allocated to the
      intervention or control group. The intervention group will receive free therapy
      including dental scaling and root planning (the standard therapy), supragingival
      prophylaxis, and oral hygiene education. The control group will only receive
      supragingival prophylaxis and oral hygiene education. Women will be followed
      throughout their pregnancy and then to childbirth. The main outcomes include
      periodontal disease status in late pregnancy and birth outcomes measured such as
      mean birth weight (grams), and mean gestational age (weeks). Periodontal disease
      will be diagnosed through a dental examination by measuring probing depth,
      clinical attachment loss and percentage of bleeding on probing (BOP) between
      gestational age of 32 and 36 weeks. Local and systemic inflammatory mediators are
      also included as main outcomes. DISCUSSION: This will be the first RCT to test
      whether treating periodontal disease among pre-conception women reduces
      periodontal disease during pregnancy and prevents adverse birth outcomes. If the
      effect of pre-pregnancy periodontal treatment is confirmed, this intervention
      could be recommended for application in low- or middle-income countries to
      improve both oral health and maternal and child health. TRIAL REGISTRATION: This
      trial is registered with Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC
      12001913.

PMID- 24321403
TI  - A text messaging intervention to promote medication adherence for patients with
      coronary heart disease: a randomized controlled trial.
AB  - OBJECTIVE: Pharmacologic treatment for secondary prevention of coronary heart
      disease (CHD) is critical to prevent adverse clinical outcomes. In a randomized
      controlled trial, we compared antiplatelet and statin adherence among patients
      with CHD who received: (1) text messages (TM) for medication reminders and
      education, (2) educational TM only, or (3) No TM. METHODS: A mobile health
      intervention delivered customized TM for 30 days. We assessed and analyzed
      medication adherence with electronic monitoring devices [Medication Event
      Monitoring System (MEMS)] by one-way ANOVA and Welch tests, two-way TM response
      rates by t-tests, and self-reported adherence (Morisky Medication Adherence
      Scale) by Repeated Measures ANOVA. RESULTS: Among 90 patients (76% male, mean age
      59.2 years), MEMS revealed patients who received TM for antiplatelets had a
      higher percentage of correct doses taken (p=0.02), percentage number of doses
      taken (p=0.01), and percentage of prescribed doses taken on schedule (p=0.01). TM
      response rates were higher for antiplatelets than statins (p=0.005). Self
      reported adherence revealed no significant differences among groups. CONCLUSION:
      TM increased adherence to antiplatelet therapy demonstrated by MEMS and TM
      responses. PRACTICE IMPLICATIONS: Feasibility and high satisfaction were
      established. Mobile health interventions show promise in promoting medication
      adherence.

PMID- 24321404
TI  - mRNA distribution of CGRP and its receptor components in the trigeminovascular
      system and other pain related structures in rat brain, and effect of
      intracerebroventricular administration of CGRP on Fos expression in the TNC.
AB  - Calcitonin gene-related peptide (CGRP) infusion in humans provokes headache
      resembling spontaneous migraine, and CGRP receptor antagonists are effective
      against acute migraine. We hypothesized that CGRP infusion in the lateral
      ventricle (LV) will induce neuronal activation reflected by increase in Fos
      expression in the trigeminal nucleus caudalis (TNC). CGRP was infused
      intracerebroventricularly (i.c.v.) in freely moving rats to circumvent factors
      like anaesthesia, acute surgery and severe hypotension, three confounding factors
      for Fos expression. TNCs were isolated 2h after CGRP infusion. The level of Fos
      protein expression in TNC was analysed by immunohistochemistry (IHC). mRNA
      expression of CGRP and its receptor components in trigeminovascular and other
      pain processing structures in the brain was also studied. CGRP i.c.v. infusion
      did not induce Fos activation in the TNC. mRNA expression profile showed that
      CGRP and its receptor components were widely distributed in trigeminovascular and
      other pain processing structures. The widespread presence of CGRP receptor mRNA
      in the various central pain pathways suggests that CGRP might play a role in
      migraine pathogenesis. 

PMID- 24321405
TI  - Selective inhibition of STAT1 reduces spinal cord injury in mice.
AB  - The signal transducer and activator of transcription 1 (STAT1) is associated with
      neuronal cell death after cerebral ischemia. However, the role of STAT1 in the
      spinal cord injury (SCI) remains unclear. Here, we examined whether STAT1
      blockade reduces neural tissue damage and locomotor impairment after SCI in mice.
      The small interfering RNA against STAT1 (STAT1 siRNA) or control non-targeting
      siRNA was injected intraperitoneally into SCI mice. Histological damage and
      locomotor function were evaluated. Inflammatory markers and apoptosis were
      determined. STAT1 siRNA treatment significantly decreased the histological damage
      following SCI. STAT1 siRNA-treated mice showed significantly improved locomotor
      function compared with the controls. Furthermore, TNF-alpha, IL-1beta, and IL-6
      levels at the injured site from the STAT1 siRNA-treated group were significantly
      reduced and IL-10 increased, in comparison with controls. The NF-kappaB
      activation and apoptosis in SCI were also inhibited. These results reveal that
      selective STAT1 inhibition reduced neural tissue damage and locomotor impairment
      by regulating inflammatory response and possibly apoptosis. STAT1 represents a
      novel therapeutic target after SCI. 

PMID- 24321406
TI  - Long-term potentiation by activation of group I metabotropic glutamate receptors
      at excitatory synapses in the spinal trigeminal subnucleus oralis.
AB  - In this study, I examined if activation of group I metabotropic glutamate
      receptors (mGluRs; mGluR1 and 5) induces long-term potentiation (LTP) at
      excitatory synapses in the ascending pathway from the spinal trigeminal subnuclei
      caudalis (Vc) to oralis (Vo), in which group I mGluRs are strongly expressed. As
      a result, the activation of group I mGluRs produced an initial short-lasting
      depression and subsequently a delayed type of long-term potentiation (LTP) of
      excitatory synaptic transmission. Analyses of paired pulse ratio and coefficient
      of variation indicated that the initial short-lasting depression was induced
      presynaptically, whereas LTP was expressed postsynaptically. In addition, the
      short-lasting depression and LTP were mostly mediated by mGluR1, and only
      partially by mGluR5 and the N-methyl-d-aspartate receptor. Thus, this study
      suggests that group I mGluRs play an important role in the expression of LTP in
      the Vc-to-Vo pathway. 

PMID- 24321407
TI  - BDNF in quinolinic acid lesioned rats after bone marrow cells transplant.
AB  - Brain-derived neurotrophic factor (BDNF) concentration was measured in the
      striatum and cortex after quinolinic acid intrastriatal lesion and
      transplantation of bone marrow cells (BMSC). The results showed a significant
      increase of the BDNF levels in the striatum and cortex of the lesioned animals
      and the ability of the transplanted cells to increase the levels of BDNF in both
      sites. This recovery of BDNF production and distribution might have beneficial
      effects and ameliorate the negative consequences of the striatal lesion, a
      mechanism of potential interest for the treatment of Huntington's disease (HD). 

PMID- 24321408
TI  - Distal enhancers: new insights into heart development and disease.
AB  - Advances in genome research have provided an unprecedented opportunity to
      investigate the function of non-coding DNA regulatory regions that control
      transcription. Large-scale studies have recently identified hundreds of thousands
      of distal enhancer elements; their discovery has revealed new insights into the
      mechanistic details of how tissue-specific gene expression patterns are
      established and maintained during development. Emerging evidence indicates that
      lineage-specific transcription factors and chromatin regulators coordinate the
      activation of distal enhancers to ensure robust control of gene expression
      programs in a cell type-specific manner. We discuss recent progress in the field
      and emphasize examples related to the cardiac lineage, where possible, as a model
      for understanding the contribution of enhancer biology to development and how
      disruption of enhancer function leads to disease. 

PMID- 24321409
TI  - Lifts and stops in proficient and dysgraphic handwriting.
AB  - In this study, the handwriting performances of dysgraphic children were compared
      to those of proficient children and adults. The task consisted in writing a
      single word at normal and fast speeds. A distinction was made between two kinds
      of pauses, which are often confounded: pen lifts, when the pen is above the
      paper, and pen stops, when it is immobile on the paper. The number and duration
      of lifts and stops were analyzed, together with the mean velocity. No difference
      in the number of lifts was observed between the three groups of writers, but the
      lift durations were shorter for adults. While dysgraphic children were able to
      write as fast as proficient children, their stops were more numerous and longer
      than those of proficient children who, themselves, made more stops than adults. A
      distinction was made between short, normal, and long, abnormal, stops. The
      results of this study suggest that pen stops are more appropriate than pen lifts
      in differentiating the handwriting fluency of dysgraphic and proficient children.

PMID- 24321410
TI  - The role of motion platform on postural instability and head vibration exposure
      at driving simulators.
AB  - This paper explains the effect of a motion platform for driving simulators on
      postural instability and head vibration exposure. The sensed head level-vehicle
      (visual cues) level longitudinal and lateral accelerations (ax,sensed=ax_head and
      ay,sensed=ay_head, ayv=ay_veh and ayv=ay_veh) were saved by using a motion
      tracking sensor and a simulation software respectively. Then, associated
      vibration dose values (VDVs) were computed at head level during the driving
      sessions. Furthermore, the postural instabilities of the participants were
      measured as longitudinal and lateral subject body centre of pressure (XCP and
      YCP, respectively) displacements just after each driving session via a balance
      platform. The results revealed that the optic-head inertial level longitudinal
      accelerations indicated a negative non-significant correlation (r=-.203,
      p=.154>.05) for the static case, whereas the optic-head inertial longitudinal
      accelerations depicted a so small negative non-significant correlation (r=-.066,
      p=.643>.05) that can be negligible for the dynamic condition. The XCP for the
      dynamic case indicated a significant higher value than the static situation
      (t(47), p<.0001). The VDVx for the dynamic case yielded a significant higher
      value than the static situation (U(47), p<.0001). The optic-head inertial lateral
      accelerations resulted a negative significant correlation (r=-.376, p=.007<.05)
      for the static platform, whereas the optic-head inertial lateral accelerations
      showed a positive significant correlation (r=.418, p=.002<.05) at dynamic
      platform condition. The VDVy for the static case indicated a significant higher
      value rather than the dynamic situation (U(47), p<.0001). The YCP for the static
      case yielded significantly higher than the dynamic situation (t(47),
      p=.001<0.05). 

PMID- 24321411
TI  - The reply.

PMID- 24321412
TI  - Too much exercise: right ventricular outflow tract tachycardia.

PMID- 24321413
TI  - Racial disparities in cardiac rehabilitation initiation and the effect on
      survival.
AB  - OBJECTIVES: To examine predictors of initiation and adherence, identify racial
      disparities, and compare the survival benefit of cardiac rehabilitation between a
      white and a unique predominantly non-white minority in an urban environment.
      DESIGN: A retrospective cohort study. SETTING: The outpatient cardiac
      rehabilitation program at Montefiore Medical Center, Bronx, New York. PATIENTS:
      Consecutive patients (n = 822) referred to outpatient cardiac rehabilitation were
      evaluated. METHODS: Baseline characteristics and outcomes were ascertained from
      medical records. Multivariate logistic regression was used to examine the
      association among initiation, age, gender, race, reason for referral, and
      copayment. Kaplan-Meier analysis was performed to evaluate mortality outcomes.
      MAIN OUTCOME MEASUREMENTS: Racial disparities in rates of initiation, adherence
      and completion, and survival benefit associated with cardiac rehabilitation.
      RESULTS: Among 822 patients referred (51.5% non-white minorities, 61.1% male),
      59.4% initiated cardiac rehabilitation. Non-white minorities initiated cardiac
      rehabilitation less often than did white patients (54.4% versus 65.2%, P = .003).
      After adjustment, white patients were 77.5% more likely to initiate cardiac
      rehabilitation (odds ratio 1.78; 95% confidence interval 1.13-2.80). Both white
      populations and non-white minorities who participated in cardiac rehabilitation
      had a lower risk of death (P = .0022). CONCLUSIONS: In a predominantly minority
      population, racial disparities exist among cardiac rehabilitation participants.
      Minorities were less likely to initiate cardiac rehabilitation. Gender, referral
      patterns, and the presence of copayment did not influence initiation. Cardiac
      rehabilitation initiation was associated with decreased mortality.

PMID- 24321414
TI  - Limb lengthening with fully implantable magnetically actuated mechanical nails
      (PHENIX((r)))-preliminary results.
AB  - Limb lengthening and deformity correction with fully implantable systems is
      becoming more and more widespread. Different actuation techniques are known and
      every system has its specific limitations in distraction control and/or
      stability. A new system with magnetic actuation offers outstanding options. The
      mechanism of the Phenix M2((r)) bone lengthening nail (Phenix Medical, France) is
      driven by a strong external magnet. The device can provide lengthening,
      shortening and bone transport. Between December 2011 and November 2012 we applied
      the nail in 10 patients with an average age of 25 years (range 15-40 years).
      There were 6 femoral and 4 tibial procedures. The intended distraction goal was
      achieved in 8 of 10 patients. In three cases we simultaneously corrected
      malalignment. Average lengthening was 4.6 cm (range 1.3-7.6 cm). Average
      distraction index was 0.85 mm/day (range 0.6-1.3mm/day). Average weight bearing
      index was 27 days/cm (range 16-37 days/cm). Three patients had revisions due to
      early distraction arrest. The early results are comparable to those of other
      intramedullary systems in the literature like the ISKD((r)), the Albizzia((r)) or
      the Fitbone((r)) system. All intramedullary procedures require accurate analysis
      and planning, advanced operative technique and close follow-up. The custom made
      design of the Phenix nail with unique options for size, stroke and locking
      provides new options for small bones and improved stability. The shortening
      option may be helpful for soft tissue problems, joint subluxation and additional
      stimulation of bone formation. Magnetic forces have to be considered and too much
      soft tissue around the nail might be a limiting factor. The magnetically actuated
      Phenix nail offers new therapeutic options in limb lengthening.

PMID- 24321415
TI  - The full spectrum of handlebar injuries in children: a decade of experience.
AB  - BACKGROUND: Traumatic paediatric handlebar injury (HBI) is known to occur with
      different vehicles, affect different body regions, and have substantial
      associated morbidity. However, previous handlebar injury research has focused on
      the specific combination of abdominal injury and bicycle riding. Our aim was to
      fully describe the epidemiology and resultant spectrum of injuries caused by a
      HBI. METHODS: Retrospective data analysis of all paediatric patients (<18 years)
      in a prospectively identified trauma registry over a 10-year period. Primary
      outcome was the HBI, its location and management. The effects of patient age,
      vehicle type, the impact region, and Injury Severity Score (ISS) were also
      evaluated. HBI patients were compared against a cohort injured while riding
      similar vehicles, but not having sustained a HBI. RESULTS: 1990 patients were
      admitted with a handlebar-equipped vehicle trauma; 236 (11.9%) having sustained a
      HBI. HBI patients were twice as likely to be aged between 6 and 14 years old
      compared with non-HBI patients (OR 2.2; 95% CI 1.5-3.2). 88.6% of the HBI
      patients sustained an isolated injury, and 45.3% had non-abdominal handlebar
      impact. There were no significant differences in median ISS (p=0.4) or need for
      operative intervention (OR 1.1; 95% CI 0.9-1.5) between HBI and non-HBI patients.
      HBI patients had a significantly longer LOS (1.8 days vs. 1.2 days; p=0.001), and
      more frequently required a major operation (OR 3.4; 95% CI 2.2-5.4). The majority
      of splenic, renal and hepatic injuries were managed conservatively. CONCLUSIONS:
      Although the majority of paediatric HBI is associated with both intra-abdominal
      injury and bicycle riding, it produces a spectrum of potentially serious injuries
      and patients are more likely to undergo major surgery. Therefore these patients
      should always be treated with a high degree of suspicion.

PMID- 24321416
TI  - Births: preliminary data for 2012.
AB  - Objectives-This report presents preliminary data for 2012 on births in the United
      States. U.S. data on births are shown by age, live-birth order, race, and
      Hispanic origin of mother. Data on marital status, cesarean delivery, preterm
      births, and low birthweight are also presented. Methods-Data in this report are
      based on 99.96% of 2012 births.Records for the few states with less than 100% of
      records received are weighted to independent control counts of all births
      received in state vital statistics offices in 2012. Comparisons are made with
      final 2011 data. Results-The preliminary number of births for the United States
      in 2012 was 3,952,937, essentially unchanged (not statistically significant) from
      2011; the general fertility rate was 63.0 births per 1,000 women aged 15-44, down
      only slightly from 2011, after declining nearly 3% a year from 2007 through 2010.
      The number of births and fertility rate either declined or were unchanged for
      most race and Hispanic origin groups from 2011 to 2012; however, both the number
      of births and the fertility rate for Asian or Pacific Islander women rose in 2012
      (7% and 4%, respectively). The birth rate for teenagers aged 15-19 was down 6% in
      2012 (29.4 births per 1,000 teenagers aged 15-19), yet another historic low for
      the United States, with rates declining for younger and older teenagers and for
      nearly all race and Hispanic origin groups. The birth rate for women in their
      early 20s also declined in 2012, to a new record low of 83.1 births per 1,000
      women. Birth rates for women in their 30s rose in 2012, as did the birth rate for
      women in their early 40s. The birth rate for women in their late 40s was
      unchanged. The nonmarital birth rate declined in 2012 (to 45.3 birth per 1,000
      unmarried women aged 15-44), whereas the number of births to unmarried women rose
      1% and the percentage of births to unmarried women was unchanged (at 40.7%). The
      cesarean delivery rate for the United States was unchanged in 2012 at 32.8%. The
      preterm birth rate fell for the sixth straight year in 2012 to 11.54%. The low
      birthweight rate also declined in 2012, to 7.99%. 

PMID- 24321417
TI  - Clinical Pregnancies and Live Births in women approaching ART: a follow-up
      analysis of 157 women after thrombophilia screening.
AB  - INTRODUCTION: The role of thrombophilia screening and antithrombotic therapy in
      unselected women undergone Assisted Reproductive Technologies (ART) is largely
      unknown. Nonetheless, in many Countries infertile women undergo thrombophilia
      screening and/or antithrombotic therapy. MATERIALS AND METHODS: We carried out a
      follow-up study. The original sample (n=1107) consisted of infertile women
      observed in 13 years. A cohort of 157 women with at least 1 cycle before
      thrombophilia test and 1 after test was investigated. All underwent thrombophilia
      screening; an antithrombotic treatment was prescribed in 216 out of 801 cycles.
      Clinical pregnancy and live birth rates were the main clinical objectives.
      RESULTS: Overall, 15 (9.6%) women carried thrombophilia. The Cox regression
      showed that LMWH alone or combined with ASA was significantly associated with the
      outcome "live birth" "live births" (p: 0.015, HR: 2.8, 95%CI: 1.2-6.6 for
      combined therapy), independently of the carriership of thrombophilia. Women with
      a lower number of attempts had a higher likelihood of delivering a live-born
      child using the combined therapy (p<0.001, HR: 0.7, 95%CI: 0.7-0.8),
      independently of the presence of thrombophilia. CONCLUSIONS: A potential benefit
      of LMWH in improving number of live births, independently of the presence of
      thrombophilia, is suggested. Universal thrombophilia screening before ART is not
      useful to discriminate women with a worse pregnancy prognosis.

PMID- 24321418
TI  - Prognostic implications of computed tomographic right ventricular dilation in
      patients with acute pulmonary embolism.
AB  - INTRODUCTION: Whether right ventricular (RV) dilation on computerized tomography
      (RVD-CT) is a useful predictor for clinical outcomes of acute pulmonary embolism
      (PE) remains debatable. Furthermore, data regarding the best combination of
      prognostic markers for predicting the adverse outcome of PE are limited.
      MATERIALS AND METHODS: The authors retrospectively reviewed 657 consecutive
      patients hospitalized at a tertiary referral center with a diagnosis of PE based
      on multi-detector row CT scan. RESULTS: Patients were allocated into an adverse
      outcome group (11% [n = 69]) or a low risk group (89% [n = 588]). Multivariate
      analysis showed that RVD-CT (RV/left ventricle [LV] diameter ratio >= 1), high
      pulmonary embolism severity index (PESI) score (class IV-V), high N-terminal-pro
      B-type natriuretic peptide (NT-proBNP,>= 1,136 pg/ml), and elevated troponin I
      (>= 0.05 ng/ml) significantly predicted an adverse outcome (odds ratio [OR] 6.26,
      95% confidence interval [CI] 2.74-14.31, p < 0.001; OR 4.71, 95% CI 2.00-11.07, p
      < 0.001; OR 2.71, 95% CI 1.15-6.39, p = 0.023; and OR 3.00, 95% CI 1.27-7.07, p =
      0.012, respectively). The addition of RVD-CT to PESI, NT-proBNP, troponin I or
      their combinations enhanced the positive predictive values and positive
      likelihood ratios of an adverse outcome. CONCLUSIONS: RVD-CT could be an
      independent prognostic factor of adverse outcomes in patients with acute PE, and
      provides additional prognostic value when combined with other prognostic factors.

PMID- 24321419
TI  - Risk factors for arterial thrombosis in antiphospholipid syndrome.
AB  - INTRODUCTION: Antiphospholipid syndrome (APS) is associated with the risk of both
      arterial and venous thrombosis. However, it is not known which factors might
      determine the location of thrombosis. MATERIALS AND METHODS: To retrospectively
      characterize factors associated with the risk of arterial thrombosis in a cohort
      of APS patients. Analysis included laboratory and clinical criteria of APS,
      together with classical cardiovascular risk factors and the possible role of
      platelet integrin alpha2beta1 (807 C/T) and alpha(IIb)beta3 (PI A1/2) genetic
      polymorphisms. We enrolled 163 APS patients (123 women and 40 men aged 21-75;
      mean age 43 years); 78 suffered from arterial thrombosis. RESULTS: There were no
      significant differences in the frequency or titers of different antiphospholipid
      antibodies with the exception of slightly increased frequency of IgG
      anticardiolipin antibodies (ACL) in the arterial thrombosis group. Livedo
      reticularis was observed significantly more often in the arterial thrombosis
      group, particularly in stroke patients. In univariate analysis arterial
      thrombosis was associated with male gender (OR-2,201; p=0,033), arterial
      hypertension (OR-2,81; p=0,002) and hypercholesterolemia (OR-3,69; p=0,001). On
      multivariate analysis arterial hypertension (OR=1,78; p=0,008) and
      hypercholesterolemia (OR=2,001; p=0,002) remained as independent risk factors for
      arterial thrombosis. Platelet glycoprotein polymorphisms studied did not show any
      significant associations with arterial thrombosis in APS patients. CONCLUSIONS:
      Among APS patients those with ACL IgG antibodies, having livedo reticularis, and
      suffering from hypertension an hypercholesterolemia are at the increased risk of
      arterial thrombosis.

PMID- 24321420
TI  - Economic evaluation of rFVIIa high initial dose compared to rFVIIa standard
      initial dose in patients with haemophilia with inhibitors using the Czech HemoRec
      registry.
AB  - INTRODUCTION: In the treatment of bleeds in haemophilia patients with inhibitors,
      a high initial dose of recombinant Factor VIIa (rFVIIa) provides at least equal
      efficacy and a similar safety profile to a standard initial dose. However, no
      pharmacoeconomic comparison between these dosing regimens has previously been
      performed. Here, we assess the pharmacoeconomics of high (>120 MUg/kg) versus
      standard (<=120 MUg/kg) initial rFVIIa dose in inhibitor patients and the impact
      of time to treatment initiation on costs and outcomes. METHODS: In a
      retrospective analysis, observational data on bleed characteristics, rFVIIa
      treatment, hospitalizations and outcomes were extracted from the Czech Republic
      HemoRec registry. Crude comparisons and generalized linear regression modelling
      (GLM; correcting for patient differences) were performed to compare costs and
      outcomes between the high and standard initial dosing groups. RESULTS: Of 314
      rFVIIa-treated bleeding episodes (12 inhibitor patients), most were spontaneous
      joint bleeds and 67.5% were treated with a high initial dose. In the crude
      comparison, high initial rFVIIa dosing was associated with a lower mean number of
      doses needed to achieve haemostasis compared with standard dosing (p<0.001), but
      higher total dose and costs (p <= 0.008). However, regression analyses revealed
      that high initial dose was associated with similar costs (p=0.891) and a shorter
      time to bleeding resolution (p=0.014). Increasing time to treatment initiation
      increased both time to bleeding resolution and total costs. CONCLUSION: Compared
      with a standard dose, a high initial rFVIIa dose may improve treatment outcomes
      without increasing costs. Early treatment initiation may reduce treatment costs.

PMID- 24321421
TI  - Efficacy of perioperative high-dose prednisolone therapy during thymectomy in
      myasthenia gravis patients.
AB  - BACKGROUND: This study aimed to investigate the benefits of administering
      perioperative high-dose prednisolone in conjunction with thymectomy in patients
      with myasthenia gravis. METHODS: We retrospectively reviewed data from patients
      with Myasthenia Gravis Foundation of America Clinical Class I to IIIB who had
      undergone an extended thymectomy between 1992 and 2009. Perioperative high-dose
      prednisolone was administered at starting doses of 10 to 20 mg and escalated up
      to 100 mg on alternate days. The treatment group comprised 70 patients receiving
      perioperative high-dose prednisolone, whereas the control group included 61
      patients not treated with preoperative steroids. The two groups were compared
      with respect to baseline clinical characteristics, incidence of postoperative
      complications, and follow-up disease status. RESULTS: Prednisolone-treated
      patients presented with more advanced disease compared to controls (Class IIB or
      greater, 42 [60.0%] versus 7 [11.3%], respectively; P < 0.001). Mean
      preoperative%FVC was lower and FEV1.0% was higher in treated patients than in
      controls (%FVC: 92.4 +/- 2.3% versus 99.5 +/- 2.4%, respectively; P = 0.037,
      FEV1.0%: 85.2 +/- 1.3% versus 81.4 +/- 0.9%, respectively; P = 0.017). The groups
      were similar in other variables including presence of thymoma, and operative
      procedure. In the treatment group, disease status was significantly improved only
      by the induction of high-dose prednisolone before the surgery (P < 0.001), and
      these patients discontinued anti-cholinesterase therapy more frequently than
      controls (P < 0.001). Moreover, the treatment group demonstrated markedly lower
      rates of postoperative crisis (12.2% versus 2.9%, respectively; P = 0.045). The
      incidence of infection, wound dehiscence, and diabetes mellitus were comparable
      between groups. Survival analysis demonstrated higher rates of treated patients
      with improved disease status at three and five years (92% and 96%, respectively)
      compared to controls (57% and 76%, respectively; P < 0.001). Likewise,
      significantly greater proportions of treated patients achieved complete stable
      remission or pharmacologic remission at three, five, and ten years (23%, 42%, and
      72%, respectively) compared to controls (10%, 20%, and 44%, respectively; P =
      0.002). CONCLUSIONS: Perioperative high-dose prednisolone therapy is a safe,
      promising strategy for managing patients with myasthenia gravis and may reduce
      the incidence of postoperative crisis while improving disease status.

PMID- 24321422
TI  - Anterior segment photography in pediatric eyes using the Lytro light field
      handheld noncontact camera.
AB  - PURPOSE: To compare anterior segment findings identified in young children using
      digital photographic images from the Lytro light field camera to those observed
      clinically. METHODS: This was a prospective study of children <9 years of age
      with an anterior segment abnormality. Clinically observed anterior segment
      examination findings for each child were recorded and several digital images of
      the anterior segment of each eye captured with the Lytro camera. The images were
      later reviewed by a masked examiner. Sensitivity of abnormal examination findings
      on Lytro imaging was calculated and compared to the clinical examination as the
      gold standard. RESULTS: A total of 157 eyes of 80 children (mean age, 4.4 years;
      range, 0.1-8.9) were included. Clinical examination revealed 206 anterior segment
      abnormalities altogether: lids/lashes (n = 21 eyes), conjunctiva/sclera (n = 28
      eyes), cornea (n = 71 eyes), anterior chamber (n = 14 eyes), iris (n = 43 eyes),
      and lens (n = 29 eyes). Review of Lytro photographs of eyes with clinically
      diagnosed anterior segment abnormality correctly identified 133 of 206 (65%) of
      all abnormalities. Additionally, 185 abnormalities in 50 children were documented
      at examination under anesthesia. CONCLUSIONS: The Lytro camera was able to
      document most abnormal anterior segment findings in un-sedated young children.
      Its unique ability to allow focus change after image capture is a significant
      improvement on prior technology.

PMID- 24321423
TI  - Stereoacuity norms for school-age children using the Frisby stereotest.
AB  - BACKGROUND: The Frisby stereotest and the TNO test for stereoscopic vision are
      popular clinical tests for assessing stereoacuity: however, reference data for
      school-age children for the Frisby stereotest are limited. This study compared
      stereoacuity results of both tests in a large sample of typically developing
      school-age children. METHODS: Primary (elementary school grades 1-6) and post
      primary (high school grades 7-11) students aged 6-16 years were recruited and
      assessed in schools. Stereoacuity thresholds were measured using the Frisby and
      TNO stereotests. Children with ocular pathology, anisometropia of >=1.00 D,
      interocular difference of visual acuity >=0.2 logMAR, or strabismus were
      excluded. RESULTS: A total of 212 children were recruited; data for 186 subjects
      were analyzed. Median Frisby stereoacuity scores were, for crossed disparity, 20
      arcsec for primary and 10 arcsec for post-primary children and, for uncrossed
      disparity, 25 arcsec (primary) and 10 arcsec (post-primary). TNO stereoacuity was
      60 arcsec for both age groups. For Frisby stereoacuity, scores of 85 arcsec
      (crossed) and 170 arcsec (uncrossed) or better were achieved by 95% of primary
      school children; scores of 85 arcsec (crossed and uncrossed) or better were
      achieved by 95% of post-primary subjects. A statistically significant difference
      in median stereoacuity scores was noted across age groups for the Frisby
      stereotest (crossed: z = 4.67, P < 0.0001; uncrossed: z = 4.67, P < 0.0001). No
      statistically significant difference in stereoacuity scores was noted with the
      TNO stereotest (z = 1.35, P = 0.18). A significant weak correlation was found
      between the Frisby and TNO stereotests (Frisby [crossed], r = 0.21 P < 0.005).
      CONCLUSIONS: These data describe normative values for the Frisby stereotest for
      children aged 6-16 years. Participants recorded significantly better stereoacuity
      scores with the Frisby stereotest than the TNO stereotest. The Frisby stereotest
      values are weakly correlated with the TNO stereoacuity test.

PMID- 24321424
TI  - Anomalous relation between axial length and retinal thickness in amblyopic
      children.
AB  - PURPOSE: To investigate the relationship between retinal thickness and axial
      length in amblyopic eyes compared to healthy eyes. METHODS: In this
      observational, transversal study, 36 amblyopic children and 30 healthy controls
      underwent full ophthalmological and orthoptic examinations, volume scanning of
      the macula with spectral domain optical coherence tomography (3D OCT-1000; Topcon
      Corporation, Tokyo, Japan), and measuring of axial length using the IOLMaster
      (Carl Zeiss Meditec AG, Jena, Germany). The average pericentral retinal thickness
      was calculated. RESULTS: A strong correlation was observed between the axial
      lengths of both eyes in the control group (R = 0.98, P < 0.01) and between the
      axial lengths of the amblyopic and fellow eye in the amblyopic group (R = 0.77, P
      < 0.01); the amblyopic and their fellow eyes were significantly shorter than the
      nonamblyopic control eyes. The pericentral retinal thickness of both eyes of an
      individual is highly correlated in nonamblyopic controls (R = 0.92, P < 0.01) and
      in amblyopic children (R = 0.82, P < 0.01). There is no significant difference in
      mean pericentral retinal thickness between healthy, amblyopic, and fellow eyes.
      In healthy eyes a moderate inverse correlation exists between axial length and
      pericentral retinal thickness (R = -0.41, P = 0.02); this relationship was not
      found in the amblyopic eyes or the normal fellow eye. CONCLUSIONS: In this
      patient cohort, there was an anomalous relation between the axial length and the
      pericentral retinal thickness in both amblyopic and their fellow eyes.

PMID- 24321425
TI  - Biomechanics of superior oblique Z-tenotomy.
AB  - BACKGROUND: A recent report suggests that 70%-80% Z-tenotomy of the superior
      oblique tendon is necessary to effectively treat A-pattern strabismus associated
      with over depression in adduction. To clarify the clinical effect, we compared
      the biomechanics of Z-tenotomy on the superior oblique tendon, superior rectus
      tendon, and isotropic latex material. METHODS: Fresh bovine superior oblique
      tendons were trimmed to 20 mm * 10 mm dimensions similar to human superior
      oblique tendon and clamped in a microtensile load cell under physiological
      conditions of temperature and humidity. Minimal preload was applied to avoid
      slackness. Tendons were elongated until failure following Z-tenotomies, made from
      opposite tendon margins, spaced 8 mm apart and each encompassing 0%, 20%, 40%,
      50%, 60%, or 80% tendon width. Digitally sampled failure force was monitored
      using a precision strain gauge. Control experiments were performed in similar
      sized specimens of bovine superior rectus tendon and isotropic latex. RESULTS:
      Progressively increasing Z-tenotomy of latex caused a linearly graded reduction
      in force. In contrast, Z-tenotomy of up to 50% in superior oblique and superior
      rectus tendons caused nonlinear reduction in force transmission that reached a
      negligible value at 50% tenotomy and greater. CONCLUSIONS: Z-tenotomy up to 50%
      progressively reduces extraocular tendon force transmission, but Z-tenotomy of
      >=50% is biomechanically equivalent in vitro to complete tenotomy.

PMID- 24321426
TI  - Congenital polycoria, trichomegaly, and hereditary congenital cataract.
AB  - We report a case of bilateral true polycoria with associated ocular and adnexal
      abnormalities in a 3-year-old boy whose family members had hereditary cataracts.
      The case was managed conservatively with optical correction and treatment for
      amblyopia. 

PMID- 24321427
TI  - Primary multifocal intraocular lens implantation for teenage-onset bilateral
      cataracts: visual results a decade after surgery in 3 siblings.
AB  - Three siblings developed bilateral, visually significant posterior subcapsular
      cataracts in their teenage years and were implanted with the SA40N Array
      Multifocal IOL. A recall examination was performed on the siblings at 12, 10, and
      9 years, respectively, after implantation. 

PMID- 24321428
TI  - Revesz syndrome masquerading as bilateral cicatricial retinopathy of prematurity.
AB  - Dyskeratosis congenita is a group of rare genetic bone marrow failure syndromes.
      Revesz syndrome, a variant disorder, is characterized by retinopathy, aplastic
      anemia, nail dystrophy, and cerebellar hypoplasia. We report the case of an 11
      month-old boy with bilateral cicatricial retinal detachments associated with
      fibrovascular proliferation. Genetic testing ultimately confirmed a diagnosis of
      Revesz syndrome, which can mimic cicatricial retinopathy of prematurity. Prompt
      referral to a hematologist expedites diagnosis and treatment. 

PMID- 24321429
TI  - Reply: To PMID 23622446.

PMID- 24321430
TI  - Reply: To PMID 23791414.

PMID- 24321431
TI  - Focal epilepsy with ictal abdominal pain: a case report.
AB  - Focal epilepsy with ictal abdominal pain is an unusual partial epilepsy
      characterized by paroxysmal episodes of abdominal or visceral pain, disturbance
      of awareness and electroencephalographic abnormalities. We describe a new case of
      ictal abdominal pain in which gastrointestinal complaints were the only
      manifestation of seizures and review the previously described pediatric patients.
      In our patient clinical findings, ictal EEG abnormalities, and a good response to
      antiepileptic drugs allowed us to make a diagnosis of focal epilepsy with ictal
      abdominal pain. This is a rare epileptic phenomenon that should be suspected in
      patients with unexplained paroxysmal abdominal pain and migraine-like symptoms.
      We suggest that, after the exclusion of more common etiologies, focal epilepsy
      with ictal abdominal pain should be considered in patients with paroxysmal
      abdominal pain and ictal EEG abnormalities. 

PMID- 24321432
TI  - A cycle of brain gain, waste and drain - a qualitative study of non-EU migrant
      doctors in Ireland.
AB  - BACKGROUND: Ireland is heavily reliant on non-EU migrant health workers to staff
      its health system. Shortages of locally trained health workers and policies which
      facilitate health worker migration have contributed to this trend. This paper
      provides insight into the experiences of non-EU migrant doctors in the Irish
      health workforce. METHOD: In-depth interviews were conducted with 37 non-EU
      migrant doctors in Ireland in 2011/2012. RESULTS: Respondents believed they had
      been recruited to fill junior hospital doctor 'service' posts. These posts are
      unpopular with locally trained doctors due to the limited career progression they
      provide. Respondents felt that their hopes for career progression and
      postgraduate training in Ireland had gone unrealised and that they were becoming
      de-skilled. As a result, most respondents were actively considering onward
      migration from Ireland. DISCUSSION & CONCLUSIONS: Failure to align the
      expectations of non-EU migrant doctors with the requirements of the health system
      has resulted in considerable frustration and a cycle of brain gain, waste and
      drain. The underlying reasons for high mobility into and out of the Irish medical
      workforce must be addressed if this cycle is to be broken. The heavy reliance on
      non-EU migrant doctors to staff the medical workforce has distracted from the
      underlying workforce challenges facing the Irish medical workforce.

PMID- 24321434
TI  - Chronic antidepressant treatment accelerates kindling epileptogenesis in rats.
AB  - OBJECTIVES: Due to the high comorbidity of epilepsy and depression,
      antidepressant treatment is commonly indicated for patients with epilepsy.
      Studies in humans and animal models suggest that selective serotonin reuptake
      inhibitors (SSRIs) may reduce seizure frequency and severity, and these drugs are
      generally considered safe for use in epilepsy. No studies have investigated the
      effects of SSRIs on epileptogenesis, the neurobiological process underlying the
      development of the epileptic state. METHODS: The effect of continuous infusion of
      the SSRI, fluoxetine (10mg/kg/day sc), versus vehicle control on amygdala
      kindling was examined in adult male Wistar rats. Seizure threshold and kindling
      rates were compared between SSRI-treated rats and controls. The study was then
      repeated examining the effect of a different SSRI, citalopram (10mg/kg/day sc),
      versus vehicle control. Hippocampal mRNA expression of the serotonin transporter
      (SERT) and the 5-HT1A receptor was examined in the brains of the rats post
      mortem. RESULTS: Treatment with either fluoxetine or citalopram significantly
      accelerated kindling epileptogenesis, as evidenced by fewer stimulations to reach
      Class V seizures compared to their respective vehicle-treated group (p<0.01 for
      both drugs). Seizure duration was also increased in fluoxetine-treated rats. No
      differences in seizure threshold were observed between treatments (p>0.05). mRNA
      analysis did not reveal any molecular changes which were common to both
      treatments. CONCLUSIONS: The rate of epileptogenesis in rats is enhanced by
      chronic treatment with SSRIs. This could potentially have implications regarding
      the effect of SSRIs on the development or progression of human epilepsy.

PMID- 24321433
TI  - Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in
      experimental acute liver failure.
AB  - Brain edema and associated astrocyte swelling leading to increased intracranial
      pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain
      levels of ammonia have been implicated in the development of brain edema in ALF.
      Cultured astrocytes treated with ammonia have been shown to undergo cell swelling
      and such swelling was associated with an increase in the plasma membrane
      expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in
      cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here,
      we examined the evolution of brain edema in AQP4-null mice and their wild type
      counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA)
      or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly
      increased brain water content in WT mice (by 1.6% +/- 0.3 and 2.3 +/- 0.4%,
      respectively). AQP4 protein was significantly increased in brain plasma membranes
      of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain
      water content did not increase in AQP4-null mice. Additionally, AQP4-null mice
      treated with either TAA or APAP showed a remarkably lesser degree of neurological
      deficits as compared to WT mice; the latter displayed an inability to maintain
      proper gait, and demonstrated a markedly reduced exploratory behavior, with the
      mice remaining in one corner of the cage with its head tilted downwards. These
      results support a central role of AQP4 in the brain edema associated with ALF.

PMID- 24321435
TI  - Longitudinal assessment of blood-brain barrier leakage during epileptogenesis in
      rats. A quantitative MRI study.
AB  - The blood-brain barrier (BBB) plays an important role in the homeostasis of the
      brain. BBB dysfunction has been implicated in the pathophysiology of various
      neurological disorders, including epilepsy in which it may contribute to disease
      progression. Precise understanding of BBB dynamics during epileptogenesis may be
      of importance for the assessment of future therapies, including BBB leakage
      blocking-agents. Longitudinal changes in BBB integrity can be studied with in
      vivo magnetic resonance imaging (MRI) in combination with paramagnetic contrast
      agents. Although this approach has shown to be suitable to detect major BBB
      leakage during the acute phase in experimental epilepsy models, so far no studies
      have provided information on dynamics of the extent of BBB leakage towards later
      phases. Therefore a sensitive and quantitative approach was used in the present
      study, involving fast T1 mapping (dynamic approach) during a steady-state
      infusion of gadobutrol, as well as pre- and post-contrast T1-weighted MRI (post
      pre approach). This was applied in an experimental epilepsy model in which
      previous MRI studies failed to detect BBB leakage during epileptogenesis. Adult
      male Sprague-Dawley rats were injected with kainic acid to induce status
      epilepticus (SE). MRI experiments were performed before SE (control) and during
      the acute (1 day) and chronic epileptic phases (6 weeks after SE). BBB leakage
      was quantified by fast T1 mapping (Look-Locker gradient echo MRI) with a time
      resolution of 48 s from 5 min before up to 45 min after 20 min step-down infusion
      of 0.2M gadobutrol. In addition, T1-weighted MRI was acquired before and 45 min
      after infusion. MRI data were compared to post-mortem microscopic analysis using
      the BBB tracer fluorescein. Our MRI data showed BBB leakage, which was evident at
      1 day and 6 weeks after SE in the hippocampus, entorhinal cortex, amygdala and
      piriform cortex. These findings were confirmed by microscopic analysis of
      fluorescein leakage. Furthermore, our MRI data revealed non-uniform BBB leakage
      throughout epileptogenesis. This study demonstrates BBB leakage in specific brain
      regions during epileptogenesis, which can be quantified using MRI. Therefore, MRI
      may be a valuable tool for experimental or clinical studies to elucidate the role
      of the BBB in epileptogenesis.

PMID- 24321436
TI  - Sirt1 and osteoarthritis. Comments on the paper by Gabay et al.: "Sirt1-deficient
      mice exhibit an altered cartilage phenotype", Joint Bone Spine 2013.

PMID- 24321437
TI  - Disseminated nocardiosis in a patient with rheumatoid arthritis treated with
      abatacept.

PMID- 24321438
TI  - Rosacea associated with etanercept.

PMID- 24321439
TI  - High pain catastrophizing scores in one-fourth of patients on biotherapy for
      spondylarthritis or rheumatoid arthritis.
AB  - OBJECTIVES: To measure catastrophizing scores in patients on biotherapy for
      spondyloarthritis (SpA) or rheumatoid arthritis (RA). METHODS: The first 140
      outpatients or day-hospital patients seen at a teaching hospital rheumatology
      department for biotherapy administration completed the validated French version
      of the Pain Catastrophizing Scale (PCS, total score ranging from 0 to 52); a
      questionnaire on perceived support and past, current, and future disease
      activity; and a questionnaire on perceived understanding of their disease by
      family and co-workers. RESULTS: PCS scores were significantly higher in the 54
      SpA patients than in the 86 RA patients (20.8 +/- 12.1 versus 17.0 +/- 13.6; P =
      0.08), as a result of a higher helplessness subscore (10.0 +/- 6.2 versus 7.8 +/-
      6.2; P = 0.046). The PCS score was >=30 in 14/54 (26%) SpA patients and in 19/86
      (22%) RA patients; physicians identified catastrophizing in only 17 of these 33
      patients. PCS scores showed moderate correlations with the AS-DAS and DAS-28 and
      slightly stronger correlations with the overall pain score (Pearson, +0.431; P =
      0.0001). SpA patients reported significantly worse understanding by their co
      workers than did RA patients (33.9 +/- 33.4 versus 53.9 +/- 36.3; P = 0.007).
      CONCLUSION: One-fourth of patients with SpA or RA had very high pain
      catastrophizing scores despite biotherapy. Pain catastrophizing was missed by the
      physicians in half the cases and was relatively independent from other follow-up
      parameters. Pain catastrophizing can jeopardize treatment outcomes and deserves
      specific management.

PMID- 24321441
TI  - Community awareness about risk factors, presentation and prevention and obstetric
      fistula in Nabitovu village, Iganga district, Uganda.
AB  - BACKGROUND: Obstetric fistula is a worldwide problem that is devastating for
      women in developing countries. The cardinal cause of obstetric fistula is
      prolonged obstructed labour and delay in seeking emergency obstetric care.
      Awareness about obstetric fistula is still low in developing countries. The
      objective was to assess the awareness about risk factors of obstetric fistulae in
      rural communities of Nabitovu village, Iganga district, Eastern Uganda. METHODS:
      A qualitative study using focus group discussion for males and females aged 18-49
      years, to explore and gain deeper understanding of their awareness of existence,
      causes, clinical presentation and preventive measures for obstetric fistula. Data
      was analyzed by thematic analysis. RESULTS: The majority of the women and a few
      men were aware about obstetric fistula, though many had misconceptions regarding
      its causes, clinical presentation and prevention. Some wrongly attributed fistula
      to misuse of family planning, having sex during the menstruation period, curses
      by relatives, sexually transmitted infections, rape and gender-based violence.
      However, others attributed the fistula to delays to access medical care, induced
      abortions, conception at an early age, utilization of traditional birth
      attendants at delivery, and some complications that could occur during surgical
      operations for difficult deliveries. CONCLUSION: Most of the community members
      interviewed were aware of the risk factors of obstetric fistula. Some
      respondents, predominantly men, had misconceptions/myths about risk factors of
      obstetric fistula as being caused by having sex during menstrual periods, poor
      usage of family planning, being a curse.

PMID- 24321440
TI  - Effects of 5-hydroxytryptamine 2C receptor agonist MK212 and 2A receptor
      antagonist MDL100907 on maternal behavior in postpartum female rats.
AB  - Maternal behavior in rats is a highly motivated and well-organized social
      behavior. Given the known roles of serotonin (5-HT) in emotion, motivation,
      social behavior, and major depression - and its known interaction with dopamine -
      it is likely that serotonin also plays a crucial role in this behavior. So far,
      there are surprisingly few studies focusing on 5-HT in maternal behavior, except
      for maternal aggression. In the present study, we examined the effects of 5-HT2C
      receptor agonism and 5-HT2A receptor antagonism on maternal behavior in
      postpartum female rats. We hypothesized that activation of 5-HT2C receptors and
      blockade of 5-HT2A receptors would produce a functionally equivalent disruption
      of maternal behavior because these two receptor subtypes often exert opposite
      effects on various brain functions and psychological processes relevant to rat
      maternal behavior. On postpartum Days 5, 7, and 9, Sprague-Dawley mother rats
      were given a single injection of 0.9% NaCl solution, the 5-HT2C agonist MK212
      (0.5, 1.0 or 2.0 mg/kg, ip), or the 5-HT2A antagonist MDL100907 (0.05, 0.5 or 2.0
      mg/kg, ip). Maternal behavior was tested 30 min before and 30 min, 120 min, 240
      min after injection. Acute injection of MK212 significantly disrupted pup
      retrieval, pup licking, pup nursing, and nest building in a dose-dependent
      fashion. At the tested doses, MDL100907 had little effect on various components
      of rat maternal behavior. Across the 3 days of testing, no apparent sensitization
      or tolerance associated with repeated administration of MK212 and MDL100907 was
      found. We concluded that rat maternal performance is critically dependent on 5
      HT2C receptors, while the role of 5-HT2A receptors is still inconclusive.
      Possible behavioral mechanisms of actions of 5-HT2C receptor in maternal behavior
      are discussed.

PMID- 24321443
TI  - A new measure for upright stability.
AB  - The control of balance is a primary objective in most human movements. In many
      cases, research or practice, it is essential to quantitatively know how good the
      balance is at a body posture or at every moment during a task. In this paper we
      suggest a new measure for postural upright stability which assigns a value to a
      body state based on the probability of avoiding a fall initiation from that
      state. The balance recovery problem is solved for a population sample using a
      strength database, and the probability of successfully maintaining the balance is
      found over the population and called the probability of recovery (PoR). It,
      therefore, describes an attribute of a body state: how possible the control of
      balance is, or how safe being at that state is. We also show the PoR calculated
      for a 3-link body model for all states on a plane, compare it to that found using
      a 2-link model, and compare it to a conventional metric: the margin of stability
      (MoS). It is shown, for example, that MoS may be very low at a state from which
      most of the people will be able to easily control their balance. 

PMID- 24321442
TI  - Impaired varus-valgus proprioception and neuromuscular stabilization in medial
      knee osteoarthritis.
AB  - Impaired proprioception and poor muscular stabilization in the frontal plane may
      lead to knee instability during functional activities, a common complaint in
      persons with knee osteoarthritis (KOA). Understanding these frontal plane
      neuromechanical properties in KOA will help elucidate the factors contributing to
      knee instability and aid in the development of targeted intervention strategies.
      The objectives of the study were to compare knee varus-valgus proprioception,
      isometric muscle strength, and active muscular contribution to stability between
      persons with medial KOA and healthy controls. We evaluated knee frontal plane
      neuromechanical parameters in 14 participants with medial KOA and 14 age- and
      gender-matched controls, using a joint driving device (JDD) with a customized
      motor and a 6-axis force sensor. Analysis of covariance with BMI as a covariate
      was used to test the differences in varus-valgus neuromechanical parameters
      between these two groups. The KOA group had impaired varus proprioception acuity
      (1.08+/-0.59 degrees  vs. 0.69+/-0.49 degrees , p<0.05), decreased normalized
      varus muscle strength (1.31+/-0.75% vs. 1.79+/-0.84% body weight, p<0.05), a
      trend toward decreased valgus strength (1.29+/-0.67% vs. 1.88+/-0.99%, p=0.054),
      and impaired ability to actively stabilize the knee in the frontal plane during
      external perturbation (4.67+/-2.86 vs. 8.26+/-5.95 Nm/degree, p<0.05). The knee
      frontal plane sensorimotor control system is compromised in persons with medial
      KOA. Our findings suggest varus-valgus control deficits in both the afferent
      input (proprioceptive acuity) and muscular effectors (muscle strength and
      capacity to stabilize the joint).

PMID- 24321444
TI  - The Dula dangerous driving index in China: an investigation of reliability and
      validity.
AB  - The aim of this study was to translate the Dula Dangerous Driving Index (DDDI)
      into Chinese and to verify its reliability and validity. A total of 246 drivers
      completed the Chinese version of the DDDI and the Driver Behavior Questionnaire
      (DBQ). Specific sociodemographic variables and traffic violations were also
      measured. A confirmatory factor analysis confirmed the internal structure of the
      DDDI, and the four-factor model was supported in China. Measures of convergent
      and criterion validity demonstrated that the Chinese DDDI was valid. Its
      convergent validity was supported by its positive relationship with the DBQ, and
      its criterion validity was tested using its relationship with self-reported
      accident involvement and traffic violations. Finally, score comparisons between
      different demographic groups revealed significant differences, thereby linking
      age and driving years to dangerous driving. 

PMID- 24321445
TI  - Role of autoimmunity in heart disease: is Chagas heart disease the definitive
      proof?

PMID- 24321447
TI  - Optical and structural properties of amorphous SexTe100-x aligned nanorods.
AB  - In the present work, we report studies on optical and structural phenomenon in as
      deposited thin films composed of aligned nanorods of amorphous SexTe100-x (x = 3,
      6, 9, and 12). In structural studies, field emission scanning electron
      microscopic (FESEM) images suggest that these thin films contain high yield of
      aligned nanorods. These nanorods show a completely amorphous nature, which is
      verified by X-ray diffraction patterns of these thin films. Optical studies
      include the measurement of spectral dependence of absorption, reflection, and
      transmission of these thin films, respectively. On the basis of optical
      absorption data, a direct optical band gap is observed. This observation of a
      direct optical band gap in these nanorods is interesting as chalcogenides
      normally show an indirect band gap, and due to this reason, these materials could
      not become very popular for semiconducting devices. Therefore, this is an
      important report and will open up new directions for the application of these
      materials in semiconducting devices. The value of this optical band gap is found
      to decrease with the increase in selenium (Se) concentration. The reflection and
      absorption data are employed to estimate the values of optical constants
      (extinction coefficient (k) and refractive index (n)). From the spectral
      dependence of these optical constants, it is found that the values of refractive
      index (n) increase, whereas the values of extinction coefficient (k) decrease
      with the increase in photon energy. The real and imaginary parts of dielectric
      constants calculated with the values of extinction coefficient (k) and refractive
      index (n), are found to vary with photon energy and dopant concentration. 

PMID- 24321446
TI  - Association of extremes of prepregnancy BMI with the clinical presentations of
      preterm birth.
AB  - OBJECTIVE: The purpose of this study was to examine associations between the
      prepregnancy maternal body mass index (BMI) across the 3 clinical presentations
      of preterm birth (PTB). STUDY DESIGN: We conducted a retrospective cohort study
      of the records of 11,726 women. The World Health Organization International
      Classification was used to categorize BMI. The primary outcome of the study was
      PTB (<37 weeks' gestation) presenting as spontaneous preterm labor, preterm
      premature rupture of the membranes, or a medical indication. We used univariable
      and multivariable logistic regression analysis to analyze the data (P < .05).
      RESULTS: We found (1) a significant increase in the overall incidence of PTB at
      the extremes of BMI, (2) a higher risk for PTB from spontaneous preterm labor at
      the lower extremes (low plus moderate thinness) of BMI (adjusted odds ratio
      [aOR], 2.4; 95% confidence interval [CI], 1.4-4.2; P = .003), (3) a higher risk
      for preterm premature rupture of the membranes at the upper extremes (obese class
      II plus III) of BMI (aOR, 1.6; 95% CI, 1.1-2.3; P = .02), and (4) a higher risk
      for a medically indicated PTB at the lower (aOR, 2.8; 95% CI, 1.4-5.6; P = .004)
      and upper (aOR, 1.5; 95% CI, 1.1-2.2; P = .02) extreme of BMI. CONCLUSION: Women
      at the extremes of prepregnancy BMI are at risk for PTB.

PMID- 24321448
TI  - Serum 25-hydroxyvitamin D in juvenile idiopathic arthritis patients in Finland.

PMID- 24321449
TI  - Knowledge, attitude and practice of antibiotics: a questionnaire study among 2500
      Chinese students.
AB  - BACKGROUND: Recently, many scientists including bacteriologists have begun to
      focus on social aspects of antibiotic management especially the knowledge,
      attitude and practice (KAP) among the general population regarding antibiotic
      use. However, relatively few works have published on the relationship between KAP
      and medical education. In this study, we analyze the present status of Chinese
      medical (MS)- and non-medical (NS) students' KAP on the use of antibiotics, and
      examine the influence of Chinese medical curriculum on the appropriate usage of
      antibiotics among medical students. METHODS: In this study, 2500 students from 3
      universities (including one medical university) in Northeastern China participate
      in the questionnaire survey on students' knowledge, attitude and practice toward
      antibiotic usage. Wilcoxon rank sum test and Chi square test were used to analyze
      questionnaire-related discrete and categorical variables respectively, in order
      to assess the impact of the medical curriculum on students' KAP towards
      antibiotics. RESULTS: 2088 (83.5%) respondents (MS-1236 and NS-852) were
      considered valid for analysis. The level of knowledge of MS on the proper use of
      antibiotics was significantly higher than that of NS (p < 0.0001). However, based
      on their responses on actual practice, MS were found to rely on antibiotics more
      than NS (p < 0.0001). Moreover, the knowledge and attitude of MS towards
      antibiotic use improved with the increase in grade with discriminate use of
      antibiotics concurrently escalating during the same period. CONCLUSIONS: This
      study indicates that Chinese medical curriculum significantly improves students'
      knowledge on antibiotics and raises their attention on antibiotic resistance that
      may result from indiscriminate use of antibiotics. The study also shows an
      excessive use of antibiotics especially among the more senior medical students,
      signifying a deficiency of antibiotics usage instruction in their curriculum.
      This might explain why there are frequent abuses of antibiotics in both hospital
      and community settings from a certain angle.

PMID- 24321450
TI  - Agronomic and genetic analysis of Suweon 542, a rice floury mutant line suitable
      for dry milling.
AB  - BACKGROUND: Producing rice flour of good quality by dry milling is necessary to
      reduce milling costs and promote the processed rice food industry. This study was
      conducted to evaluate the dry milling properties of Suweon 542, a floury
      endosperm mutant, and identify the chromosomal region responsible for the floury
      endosperm characteristics. RESULTS: Compared with the wild type, after dry
      milling process, the grain hardness of Suweon 542 was significantly lower because
      of its round and loosely packed starch granules. Also, the flour of Suweon 542
      had significantly smaller particles and less damaged starch than Namil and other
      rice cultivars and its particle size distribution was similar to a commercial
      wheat cultivar. Considering that the yield loss of Suweon 542 due to its floury
      endosperm was largely compensated for by an increased number of spikelets per
      panicle, Suweon 542 has potential value as a raw material for rice flour
      production. Association analysis using 70 genome-wide SSR markers and 94 F2
      plants derived from Suweon 542/Milyang 23 showed that markers on chromosome 5
      explained a large portion of the variation in floury grains percentage (FGP).
      Further analysis with an increased number of SSR markers revealed that the floury
      endosperm of Suweon 542 was directed by a major recessive locus, flo7(t), located
      in the 19.33-19.86 Mbp region of chromosome 5, with RM18639 explaining 92.2% of
      FGP variation in the F2 population. CONCLUSIONS: The floury endosperm of Suweon
      542 is suitable for dry milling, with a small flour particle size and low damaged
      starch content. Further physical mapping of flo7(t), the floury endosperm locus
      of Suweon 542, would facilitate efficient breeding of rice cultivars with proper
      dry milling adaptability that can be used in the processed rice food industry.

PMID- 24321451
TI  - Induced pluripotent stem cells from patients with human fibrodysplasia ossificans
      progressiva show increased mineralization and cartilage formation.
AB  - BACKGROUND: Abnormal activation of endochondral bone formation in soft tissues
      causes significant medical diseases associated with disability and pain.
      Hyperactive mutations in the bone morphogenetic protein (BMP) type 1 receptor
      ACVR1 lead to fibrodysplasia ossificans progressiva (FOP), a rare genetic
      disorder characterized by progressive ossification in soft tissues. However, the
      specific cellular mechanisms are unclear. In addition, the difficulty obtaining
      tissue samples from FOP patients and the limitations in mouse models of FOP
      hamper our ability to dissect the pathogenesis of FOP. METHODS: To address these
      challenges and develop a "disease model in a dish", we created human induced
      pluripotent stem cells (iPS cells) derived from normal and FOP dermal fibroblasts
      by two separate methods, retroviral integration or integration-free episomal
      vectors. We tested if the ability to contribute to different steps of
      endochondral bone formation was different in FOP vs. control iPS cells. RESULTS:
      Remarkably, FOP iPS cells showed increased mineralization and enhanced
      chondrogenesis in vitro. The mineralization phenotypes could be suppressed with a
      small-molecule inhibitor of BMP signaling, DMH1. Our results indicate that the
      FOP ACVR1 R206H mutation favors chondrogenesis and increases mineral deposition
      in vitro. CONCLUSIONS: Our findings establish a FOP disease cell model for in
      vitro experimentation and provide a proof-of-concept for using human iPS cell
      models to understand human skeletal disorders.

PMID- 24321452
TI  - The schizophrenia susceptibility gene DTNBP1 modulates AMPAR synaptic
      transmission and plasticity in the hippocampus of juvenile DBA/2J mice.
AB  - The dystrobrevin binding protein (DTNBP) 1 gene has emerged over the last decade
      as a potential susceptibility locus for schizophrenia. While no causative
      mutations have been found, reduced expression of the encoded protein, dysbindin,
      was reported in patients. Dysbindin likely plays a role in the neuronal
      trafficking of proteins including receptors. One important pathway suspected to
      be affected in schizophrenia is the fast excitatory glutamatergic transmission
      mediated by AMPA receptors. Here, we investigated excitatory synaptic
      transmission and plasticity in hippocampal neurons from dysbindin-deficient sandy
      mice bred on the DBA/2J strain. In cultured neurons an enhancement of AMPAR
      responses was observed. The enhancement of AMPAR-mediated transmission was
      confirmed in hippocampal CA3-CA1 synapses, and was not associated with changes in
      the expression of GluA1-4 subunits or an increase in GluR2-lacking receptor
      complexes. Lastly, an enhancement in LTP was also found in these mice. These data
      provide compelling evidence that dysbindin, a widely suspected susceptibility
      protein in schizophrenia, is important for AMPAR-mediated synaptic transmission
      and plasticity in the developing hippocampus. 

PMID- 24321453
TI  - Excitotoxic potential of exogenous ferritin and apoferritin: changes in ambient
      level of glutamate and synaptic vesicle acidification in brain nerve terminals.
AB  - Ferritin, an iron storage protein, is present in the serum and cerebrospinal
      fluid, has receptors on the cell surface, able to penetrate the brain-blood
      barrier, can be secreted from the cells, and leaks from destroyed cell in insult
      and brain trauma. The effect of exogenous ferritin on the key characteristic of
      glutamatergic neurotransmission was assessed in rat brain nerve terminals
      (synaptosomes). Exogenous ferritin (80 MUg/ml, iron content 0.7%) significantly
      increased the ambient level of L-[(14)C]glutamate (0.200+/-0.015 versus 0.368+/
      0.016 nmol/mg of protein) and endogenous glutamate (fluorimetric glutamate
      dehydrogenase assay) in the nerve terminals. This increase was not a result of
      augmentation of tonic release because the velocity of tonic release of L
      [(14)C]glutamate was not changed significantly in ferritin-treated synaptosomes
      as compared to the control. Ferritin caused a decrease in synaptic vesicle
      acidification that was shown using fluorescent dye acridine orange. Iron
      dependence of the effects of ferritin was analyzed with apoferritin (0.0025%
      residual iron). Apoferritin weakly affected the proton electrochemical gradient
      of synaptic vesicles but increased the ambient level and decreased the initial
      velocity of uptake of L-[(14)C]glutamate by synaptosomes, nevertheless these
      effects were ~30% lesser than those caused by ferritin. Exogenous ferritin can
      provoke the development of excitotoxicity increasing the ambient level of
      glutamate and lowering synaptic vesicle acidification and glutamate uptake in the
      nerve terminals, however these effects are not completely iron-dependent. Thus,
      in the CNS exogenous ferritin can act as a modulator of glutamate homeostasis in
      iron-dependent and iron-independent manner.

PMID- 24321455
TI  - Galphaz regulates BDNF-induction of axon growth in cortical neurons.
AB  - The disruption of neurotransmitter and neurotrophic factor signaling in the
      central nervous system (CNS) is implicated as the root cause of neuropsychiatric
      disorders, including schizophrenia, epilepsy, chronic pain, and depression.
      Therefore, identifying the underlying molecular mechanisms by which
      neurotransmitter and neurotrophic factor signaling regulates neuronal survival or
      growth may facilitate identification of more effective therapies for these
      disorders. Previously, our lab found that the heterotrimeric G protein, Gz,
      mediates crosstalk between G protein-coupled receptors and neurotrophin signaling
      in the neural cell line PC12. These data, combined with Galphaz expression
      profiles--predominantly in neuronal cells with higher expression levels
      corresponding to developmental times of target tissue innervation--suggested that
      Galphaz may play an important role in neurotrophin signaling and neuronal
      development. Here, we provide evidence in cortical neurons, both manipulated ex
      vivo and those cultured from Gz knockout mice, that Galphaz is localized to
      axonal growth cones and plays a significant role in the development of axons of
      cortical neurons in the CNS. Our findings indicate that Galphaz inhibits BDNF
      stimulated axon growth in cortical neurons, establishing an endogenous role for
      Galphaz in regulating neurotrophin signaling in the CNS.

PMID- 24321454
TI  - The Anaphase-Promoting Complex (APC) ubiquitin ligase regulates GABA transmission
      at the C. elegans neuromuscular junction.
AB  - Regulation of both excitatory and inhibitory synaptic transmission is critical
      for proper nervous system function. Aberrant synaptic signaling, including
      altered excitatory to inhibitory balance, is observed in numerous neurological
      diseases. The ubiquitin enzyme system controls the abundance of many synaptic
      proteins and thus plays a key role in regulating synaptic transmission. The
      Anaphase-Promoting Complex (APC) is a multi-subunit ubiquitin ligase that was
      originally discovered as a key regulator of protein turnover during the cell
      cycle. More recently, the APC has been shown to function in postmitotic neurons,
      where it regulates diverse processes such as synapse development and synaptic
      transmission at glutamatergic synapses. Here we report that the APC regulates
      synaptic GABA signaling by acting in motor neurons to control the balance of
      excitatory (acetylcholine) to inhibitory (GABA) transmission at the
      Caenorhabditis elegans neuromuscular junction (NMJ). Loss-of-function mutants in
      multiple APC subunits have increased muscle excitation at the NMJ; this phenotype
      is rescued by expression of the missing subunit in GABA neurons. Quantitative
      imaging and electrophysiological analyses indicate that APC mutants have
      decreased GABA release but normal cholinergic transmission. Consistent with this,
      APC mutants exhibit convulsions in a seizure assay sensitive to reductions in
      GABA signaling. Previous studies in other systems showed that the APC can
      negatively regulate the levels of the active zone protein SYD-2 Liprin-alpha.
      Similarly, we found that SYD-2 accumulates in APC mutants at GABAergic
      presynaptic sites. Finally, we found that the APC subunit EMB-27 CDC16 can
      localize to presynapses in GABA neurons. Together, our data suggest a model in
      which the APC acts at GABAergic presynapses to promote GABA release and inhibit
      muscle excitation. These findings are the first evidence that the APC regulates
      transmission at inhibitory synapses and have implications for understanding
      nervous system pathologies, such as epilepsy, that are characterized by
      misregulated GABA signaling. 

PMID- 24321456
TI  - The impact of product information and trials on demand for smokeless tobacco and
      cigarettes: evidence from experimental auctions.
AB  - INTRODUCTION: Epidemiological and toxicological evidence suggests lower risk of
      smokeless tobacco (ST) products compared to cigarettes. Less is known, however,
      about consumer perceptions and use of novel forms of ST, including snus and
      dissolvable tobacco. METHODS: In this study, we conducted in-person experimental
      auctions in Buffalo, NY, Columbia, SC, and Selinsgrove, PA with 571 smokers to
      test the impact of information and product trials on smokers' preferences.
      Auctions were conducted between November 2010-November 2011. RESULTS: We found no
      evidence of an impact of product trials on demand in our auctions. Anti-ST
      information increased demand for cigarettes when presented alone, but when
      presented with pro-ST information it decreased demand for cigarettes. It did not
      decrease demand for ST products. Anti-smoking information increased demand for ST
      products, but did not affect cigarette demand. CONCLUSIONS: These findings
      suggest that credible and effective communications about tobacco harm reduction
      should reinforce the negative effects of smoking.

PMID- 24321457
TI  - A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti
      TNF treatment in Japanese patients with rheumatoid arthritis.
AB  - OBJECTIVES: Recent genome-wide association studies disclosed that several single
      nucleotide polymorphisms (SNPs), including tumour necrosis factor (TNF) receptor
      associated factor 1 (TRAF1) (+16860A/G), are associated with the pathophysiology
      of rheumatoid arthritis (RA). We assessed the usefulness of TRAF1 genotyping as a
      genetic predictor of the response to anti-TNF treatment in Japanese RA patients.
      METHODS: TRAF1 (+16860A/G) was genotyped using the TaqMan SNP genotyping assay in
      101 Japanese RA patients treated with anti-TNF drugs for >24 weeks. We
      retrospectively analysed the association between SNP and the clinical response to
      treatment. TRAF1 mRNA and protein expression was also evaluated in CD4+, CD8+,
      CD14+, or CD19+ cells from 25 healthy subjects using quantitative polymerase
      chain reaction and intracellular staining flow cytometry, respectively. RESULTS:
      No statistical difference in DAS28-ESR at baseline was observed between the
      patient groups with the AA, AG, or GG genotype. The GG genotype was more frequent
      in non-responders than in good or moderate responders [odds ratio (OR) 7.4, 95%
      confidence interval (CI) 1.5-37.5]. The non-responders possessed the G allele
      more frequently than the good or moderate responders (OR 3.5, 95% CI 1.4-9.0).
      TRAF1 protein expression increased significantly in CD14+ monocytes from healthy
      subjects with the GG genotype compared with that in subjects with the AA or AG
      genotype. CONCLUSIONS: TRAF1 (+16860A/G) may be useful for predicting the
      clinical response to anti-TNF treatment and may contribute to resistance to
      treatment in RA patients with the GG genotype by increasing the TRAF1 expression
      in circulating inflammatory cells.

PMID- 24321458
TI  - Rapidly progressive quadriparesis heralding disseminated coccidioidomycosis in an
      immunocompetent patient.
AB  - Coccidioides species are dimorphic fungi endemic to southwestern USA and northern
      Mexico. Disseminated coccidioidomycosis is rare with an estimated incidence of 1%
      in affected individuals and usually presents as meningitis when the central
      nervous system is involved. Spinal involvement with coccidioidomycosis, though
      not uncommon, predominantly manifests as osseous involvement leading to
      osteomyelitis and epidural abscess formation. Progressive quadriparesis as a
      presenting symptom secondary to intramedullary spinal cord coccidioidomycosis is
      very unusual and to our knowledge has not been described. We report a patient
      with disseminated coccidioidomycosis who presented with rapidly progressive
      quadriparesis due to cervical intramedullary spinal cord involvement. The absence
      of known coccidioidomycosis with atypical clinical presentation made the
      diagnosis elusive, requiring emergent cervical laminectomies with dural biopsy
      for decompression of the spinal cord and confirmation of the diagnosis. The
      patient eventually succumbed to the progressive course of the disease. Although
      rare, disseminated coccidioidomycosis can present as new, rapidly progressing
      quadriparesis in patients who have traveled to endemic areas. A high index of
      suspicion in such patients with appropriately directed laboratory investigations
      and consideration of early biopsy might unravel the diagnosis facilitating early
      antifungal treatment with the potential to minimize morbidity and mortality
      associated with disseminated coccidioidomycosis. 

PMID- 24321459
TI  - Thromboembolic stroke associated with thoracic outlet syndrome.
AB  - Thoracic outlet syndrome occurs due to compression of the neurovascular
      structures as they exit the thorax. Subclavian arterial compression is usually
      due to a cervical rib, and is rarely associated with thromboembolic stroke. The
      mechanism of cerebral embolisation associated with the thoracic outlet syndrome
      is poorly understood, but may be due to retrograde propagation of thrombus or
      transient retrograde flow within the subclavian artery exacerbated by arm
      abduction. We report an illustrative patient and review the clinical features,
      imaging findings and management of stroke associated with thoracic outlet
      syndrome.

PMID- 24321461
TI  - Spectrum of renal pathology in adult patients with congenital renal anomalies-a
      series from a tertiary cancer center.
AB  - Congenital renal anomalies (CRAs) detected in adults include horseshoe kidney
      (HK), crossed renal ectopia, and malrotation. Congenital renal anomalies are
      rare, and renal lesions associated with CRA are rarer. Thirteen patients (11 men
      and 2 women) were referred to our center with renal masses in the context of
      CRAs, which included HK (10 cases), crossed renal ectopia (2 cases), and a pelvic
      kidney (1 case). The mean age at diagnosis was 60 years (37-76 years). All
      patients were treated with open surgery; 10, partial nephrectomies; 4, radical
      nephrectomies; and 1, nephroureterectomy with division of the renal isthmus.
      Pathology ranged from benign (simple cortical cysts, chronic pyelonephritis with
      secondary hydronephrosis) to malignant (12 cases of renal cell carcinomas [RCCs]
      and 1 case of urothelial carcinoma). Two patients of HKs presented with bilateral
      renal masses. The size of the RCC ranged from 2.5 to 13 cm. There were 11 cases
      of clear cell RCC, 1 case of papillary RCC (type 1), and 1 case of urothelial
      carcinoma. All the cases of RCC had negative surgical margins. Follow-up
      available in all patients ranged from 1 month up to 49 months. None of the
      patients developed any locoregional recurrences or distant metastases. In this
      patient cohort, the most common congenital anomaly associated with RCC is HK. All
      tumors behaved in an indolent fashion with prognosis related to pathologic tumor
      stage. Partial nephrectomy is a safe and effective procedure in appropriately
      selected patients. 

PMID- 24321462
TI  - The genetics of interdigitating dendritic cell sarcoma share some changes with
      Langerhans cell histiocytosis in select cases.
AB  - Histiocytic disorders have been noted to have evidence of transdifferentiation;
      examples of cases with combinations of different lineages have been shown. In our
      index case, we identified interdigitating dendritic cell (IDC) differentiation in
      a case of Langerhans cell histiocytosis (LCH). Little is currently known about
      the genetics of IDC sarcoma (IDCS) because they are exceedingly rare. Using array
      comparative genomic hybridization (aCGH), we evaluated 4 cases of IDCS and
      compared them with our index case, as well as genetic abnormalities previously
      found in LCH. Four cases of paraffin-embedded samples of IDCS and 1 case of LCH
      with IDC differentiation were evaluated using aCGH. Array CGH results showed no
      abnormalities in a case of LCH with interdigitating cell differentiation. In 3 of
      4 cases of IDCS, genetic abnormalities were identified; 1 case had no
      identifiable abnormalities. Interdigitating dendritic cell sarcoma case 1 had
      gains of 3q and 13q; IDCS case 2 had trisomy 12; IDCS case 3 had deletions of 7p,
      12p, 16p, 18q, 19q, and 22q; and IDCS case 4 had no detectable abnormalities. Our
      index case, LCH with IDC differentiation, showed no abnormalities by aCGH. A
      number of LCH cases do not have detectable genetic abnormalities. In contrast, 3
      of 4 cases of IDCS evaluated had identifiable abnormalities by aCGH. Furthermore,
      2 of these shared abnormalities, albeit of large genetic regions, with published
      abnormalities seen in LCH. No recurrent abnormalities were identified in the IDCS
      cases. However, the possibility of a relationship between IDCS and LCH cannot be
      entirely excluded by these results. 

PMID- 24321463
TI  - Immunohistochemistry-based subtyping of breast carcinoma in Egyptian women: a
      clinicopathologic study on 125 patients.
AB  - Breast carcinoma is a heterogeneous disease affected by patients' ethnicity. Gene
      expression analysis identified several molecular subtypes, and similar subtyping
      has now been found to be feasible using immunohistochemistry. This study
      estimated the distribution of intrinsic breast cancer subtypes using estrogen
      receptor, progesterone receptor, human epidermal growth factor receptor 2
      (Her2/neu), and cytokeratin 5/6 immunostaining in a cohort of 125 Egyptian women
      diagnosed as having invasive breast carcinoma. Associations with
      clinicopathologic variables and the prognostic markers Bcl-2 and Cyclin D1 were
      investigated and statistically analyzed. Population difference in breast cancer
      subtypes was detected, suggesting etiologic and genetic heterogeneity among
      demographic groups. As reported worldwide, most tumors were luminal A (39.2%),
      but basal-like and unclassified subtypes had higher proportions among our cohort
      (16.8% and 16%, respectively), particularly in premenopausal patients (P =
      .0001), in contrast to postmenopausal African Americans, premenopausal European
      Americans, and other populations. Her2-overexpressing subtype was the least
      common subtype (13.65%) among our patients, although it is more common in Asians.
      Basal-like and unclassified carcinomas were more frequently grade 3 neoplasms (P
      = .035). Lobular histology was distributed among luminal A, B and unclassified
      subtypes (P = .006). The highest frequency of nodal positivity was associated
      with Her2 overexpressing carcinomas (94.1%, P = .0001). Luminal and unclassified
      carcinomas more likely expressed Bcl-2 (P = .011) and Cyclin D1 (P = .0001),
      whereas basal and Her2 subtypes had the lowest expression levels.
      Immunohistochemistry-based subtyping can be helpful in separating breast
      carcinoma into subtypes that vary in distribution among different populations.
      These subtypes have distinct clinicopathologic features and diverse
      prognostication, which may imply different therapeutic options for each subtype. 

PMID- 24321460
TI  - Reproductive factors and risk of hormone receptor positive and negative breast
      cancer: a cohort study.
AB  - BACKGROUND: The association of reproductive factors with hormone receptor (HR)
      negative breast tumors remains uncertain. METHODS: Within the EPIC cohort, Cox
      proportional hazards models were used to describe the relationships of
      reproductive factors (menarcheal age, time between menarche and first pregnancy,
      parity, number of children, age at first and last pregnancies, time since last
      full-term childbirth, breastfeeding, age at menopause, ever having an abortion
      and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n
      = 3,567) breast tumors. RESULTS: A later first full-term childbirth was
      associated with increased risk of ER+PR+ tumors but not with risk of ER-PR-
      tumors (>=35 vs. <=19 years HR: 1.47 [95% CI 1.15-1.88] p(trend) < 0.001 for
      ER+PR+ tumors; >=35 vs. <=19 years HR: 0.93 [95% CI 0.53-1.65] p(trend) = 0.96
      for ER-PR- tumors; P(het) = 0.03). The risk associations of menarcheal age, and
      time period between menarche and first full-term childbirth with ER-PR-tumors
      were in the similar direction with risk of ER+PR+ tumors (p(het) = 0.50),
      although weaker in magnitude and statistically only borderline significant. Other
      parity related factors such as ever a full-term birth, number of births, age- and
      time since last birth were associated only with ER+PR+ malignancies, however no
      statistical heterogeneity between breast cancer subtypes was observed.
      Breastfeeding and OC use were generally not associated with breast cancer subtype
      risk. CONCLUSION: Our study provides possible evidence that age at menarche, and
      time between menarche and first full-term childbirth may be associated with the
      etiology of both HR-negative and HR-positive malignancies, although the
      associations with HR-negative breast cancer were only borderline significant.

PMID- 24321464
TI  - The role of immunohistochemistry in the diagnosis of flat urothelial lesions: a
      study using CK20, CK5/6, P53, Cd138, and Her2/Neu.
AB  - Although differentiating reactive urothelial atypia from urothelial carcinoma in
      situ (CIS) relies primarily on histologic evaluation, confirming the morphologic
      impression using immunohistochemistry (IHC) has been increasingly used in routine
      clinical practice. The aims of this study are to confirm the utility of commonly
      used markers (CK20, P53) and to test the performance of CK5/6, CD138, and
      Her2/Neu in the diagnosis of CIS. Using a tissue microarray comprising 52 cases
      of normal/reactive urothelium and 45 cases of CIS, the IHC evaluation of 5
      markers was undertaken. Although the individual specificity of CK20, P53, and
      Her2/Neu was high (94%, 90%, and 93%, respectively), their sensitivity for CIS
      detection was lower, with the most sensitive marker being HER2/Neu (63%). Whereas
      78% of CIS shows positivity of at least 2 of those 3 markers, only 1 case of
      reactive urothelium shows positivity for 2 of those 3 markers. The discriminatory
      performance of CK5/6 and CD138 was poor. In conclusion, HER2/Neu can be added to
      a panel of CK20 and P53 to help differentiate reactive atypia from CIS in
      difficult cases. Positive staining for at least 2 of the 3 antibodies (CK20, P53,
      and HER2/Neu) is strongly associated with CIS. However, the histologic findings
      should be a primary determinant in the diagnosis of flat urothelial lesions, with
      IHC playing a supportive confirmatory role. 

PMID- 24321465
TI  - Parotid and periparotid parathyroid ectopy.

PMID- 24321466
TI  - Outcomes of emergency or physical examination-indicated cerclage in twin
      pregnancies compared to singleton pregnancies.
AB  - OBJECTIVE: To report the obstetrical outcomes in patients with twin pregnancies
      who underwent an emergency/physical exam-indicated cerclage and to compare them
      to patients with singleton pregnancies undergoing the same procedure. STUDY
      DESIGN: Patients who underwent emergency/physical exam-indicated cerclage in the
      second trimester in one maternal-fetal medicine practice from July 1997 to March
      2012 were reviewed. We defined an emergency/physical exam-indicated cerclage as
      any cerclage placed in a patient with a dilated cervix on examination or
      membranes visible at the external cervical os on speculum examination. We
      compared outcomes between patients with singleton and twin pregnancies using non
      parametric testing. RESULTS: There were 43 patients (12 twin and 31 singleton
      pregnancies) who underwent emergency/physical exam-indicated cerclage placement.
      The median gestational age at cerclage placement, cervical dilation, maternal
      age, and cerclage type were similar between the groups. Comparing twins to
      singletons, the median time from cerclage placement to delivery was similar (92
      vs. 106 days, p=0.330), as was the median gestational age at delivery (33.5 vs.
      35.0 weeks, p=0.244). The likelihood of delivery at >32 weeks (75.0% vs. 71.0%,
      p>0.999) and the likelihood of neonatal survival to discharge (83.3% vs. 83.9%,
      p>0.999) were also similar. CONCLUSIONS: Emergency/physical exam-indicated
      cerclage in twin pregnancies can be associated with favorable outcomes, including
      a high likelihood of delivery at >32 weeks and a high likelihood of survival.
      Their outcomes appear similar to singleton pregnancies. Cerclage should be
      considered an option for patients with twin pregnancies and a dilated cervix in
      the second trimester.

PMID- 24321467
TI  - A comparative study of lung toxicity in rats induced by three types of
      nanomaterials.
AB  - The public is increasingly exposed to various engineered nanomaterials because of
      their mass production and wide application. Even when the biological effects of
      nanomaterials have been assessed, the underlying mechanisms of action in vivo are
      poorly understood. The present study was designed to seek a simple, effective,
      and oxidative stress-based biomarker system used for screening toxicity of
      nanomaterials. Nano-ferroso-ferric oxide (nano-Fe3O4), nano-silicon dioxide (nano
      SiO2), and single-walled carbon nanotubes (SWCNTs) were dispersed in corn oil and
      characterized using transmission electron microscopy (TEM). Rats were exposed to
      the three nanomaterials by intratracheal instillation once every 2 days for 5
      weeks. We investigated their lung oxidative and inflammatory damage by
      bronchoalveolar lavage fluid (BALF) detection and comparative proteomics by lung
      tissue. Two-dimensional electrophoresis (2-DE) of proteins isolated from the lung
      tissue, followed by matrix-assisted laser desorption-ionization time-of-flight
      mass spectrometry, was performed. In the present study, we chose to detect
      lactate dehydrogenase, total antioxidant capacity, superoxide dismutase, and
      malondialdehyde as the biomarker system for screening the oxidative stress of
      nanomaterials and IL-6 as the inflammatory biomarker in BALF. Proteomics analysis
      revealed 17 differentially expressed proteins compared with the control group:
      nine were upregulated and eight were downregulated. Our results indicated that
      exposure by intratracheal instillation to any of the three typical nanomaterials
      may cause lung damage through oxidative damage and/or an inflammatory reaction. 

PMID- 24321468
TI  - Diabetes in North America and the Caribbean: an update.
AB  - The North America and Caribbean (NAC) Region faces a high burden of diabetes. In
      2013, the number of children (aged 0-14 years) with type 1 diabetes was 108,600,
      with 16.7 new cases diagnosed per 100,000 children. Furthermore, there were
      36,755,500 individuals with diabetes (mostly type 2 diabetes) in adults (20-79
      years), and an additional 44,277,700 individuals had impaired glucose tolerance.
      The age-adjusted prevalence of diabetes in adults was 9.6%; the second highest
      among the seven Regions of the International Diabetes Federation. This estimate
      is expected to grow to 9.9% by 2035. There was some heterogeneity in the
      estimates within the Region with the age-adjusted prevalence for the USA
      estimated at 9.2%, 7.9% for Canada, 12.6% for Mexico, and 9.6% for the Caribbean
      islands. Mortality due to diabetes in the NAC Region is not limited to older age
      groups, with 37.6% of deaths occurring in people under the age of 60. The
      economic impact was also enormous, with healthcare expenditure due to diabetes
      estimated at 263.2 billion USD for 2013 - the highest of all IDF Regions.
      Diabetes threatens the public health and economies of countries in the NAC
      Region, and efforts in prevention and management must be intensified in order to
      surmount this growing problem. 

PMID- 24321469
TI  - Immunogammopathies and acquired vitelliform detachments: a report of four cases.
AB  - PURPOSE: To describe the nature and evolution of acquired macular detachments in
      patients with immunogammopathies and to propose a mechanism for their
      development. DESIGN: Retrospective observational case series. METHODS: Three
      patients with multiple myeloma and 1 with light chain deposition disease were
      diagnosed with vitelliform macular detachments based on clinical examination,
      fundus autofluorescence, fluorescein angiography, and optical coherence
      tomography. These patients were followed over time and their clinical
      examinations and imaging studies were compared and contrasted. RESULTS: Three
      patients (5 eyes) with multiple myeloma and 1 patient (2 eyes) with light chain
      deposition disease presented with acquired macular yellowish subretinal deposits
      on funduscopic examination that corresponded to hyperautofluorescent lesions on
      fundus autofluorescence imaging and subretinal hyperreflective material on
      spectral-domain optical coherence tomography. One patient (2 eyes) had diffuse
      serous retinal detachments involving not only the macular region but also the
      midperiphery of the retina. These acquired macular vitelliform detachments were
      not associated with signs of hyperviscosity retinopathy in 5 eyes and resolved
      after successful treatment of the multiple myeloma in 6 eyes. CONCLUSION:
      Patients with an immunogammopathy such as multiple myeloma or light chain
      deposition disease may develop serous elevations of the macula that we classify
      as acquired vitelliform detachments using multimodal imaging. Appropriate
      evaluation including serum protein electrophoresis and hematology consultation
      should be considered in the management of patients with acquired vitelliform
      detachments of uncertain etiology.

PMID- 24321470
TI  - Characteristics of rhegmatogenous retinal detachment after refractive surgery:
      comparison with myopic eyes with retinal detachment.
AB  - PURPOSE: To evaluate the characteristics of rhegmatogenous retinal detachment
      (RD) in patients with previous laser in situ keratomileusis (LASIK) and compare
      them to RD in patients with previous laser assisted subepithelial keratomileusis
      (LASEK) and myopic patients with no previous refractive surgery. DESIGN:
      Retrospective, comparative case series. METHODS: In 106 eyes of 106 patients with
      RD, patients with previous refractive surgery included 21 eyes after LASIK and 13
      eyes after LASEK; 72 myopic patients with refractive errors of -3.0 diopters or
      less were grouped as the R (-) group. Characteristics of RD included distribution
      of RD and associated retinal breaks, location and number of retinal breaks,
      presence of lattice degeneration, and axial lengths. RESULTS: The mean interval
      between refractive surgery and the onset of rhegmatogenous RD was 63.7 +/- 43.5
      months, occurring across a broad spectrum of time intervals. There were no
      significant differences among the LASIK group, the LASEK group, and the R (-)
      group in axial length (26.8 mm vs 26.4 mm vs 26.9 mm, respectively); in mean
      number of retinal holes/tears, (2.1/1.5, 0.9/1.4, 1.5/1.6, respectively); or in
      the presence of lattice degeneration (52.4% vs 46.2% vs 43.1%, respectively).
      Distribution of RD and associated retinal breaks were also not significantly
      different; retinal holes and tears were more prevalent in the temporal quadrants,
      and inferotemporal quadrants were the most commonly detached areas in both the
      LASEK and LASIK groups and in the R (-) group. CONCLUSIONS: Myopia is a well
      known risk factor for rhegmatogenous RD and may contribute more to the
      development of RD in myopic patients after refractive surgery, rather than
      refractive surgery itself.

PMID- 24321471
TI  - Clinic-based glaucoma care in the era of surgical subspecialization.
AB  - PURPOSE: To evaluate the impact of surgeon practice profile on clinic-based
      glaucoma care. DESIGN: Population-based study of glaucoma care patterns in
      Ontario, Canada from 2000-2010. METHODS: Using comprehensive physician services
      data from the Ontario Health Insurance Plan database, ophthalmologists were
      divided into 5 surgical practice subgroups. The role of each subgroup in the
      provision of glaucoma care was evaluated. Consultations and office visits were
      used to assess nonsurgical care, while laser trabeculoplasty procedures were used
      to assess clinic-based procedural care. RESULTS: Between 2000 and 2010, the
      population rate of glaucoma consultations and follow-up visits provided by
      ophthalmologists who do not perform incisional glaucoma surgery increased at
      average annual rates of 1.6% (P < .0002) and 3.3% (P < .0001), respectively. In
      contrast, no significant growth in the rate of glaucoma consultations or follow
      up visits provided by glaucoma surgeons was observed (0.8%/year [P = .2] for
      consultations; 0.2%/year [P = .6] for follow-up visits). Between 2000 and 2010,
      the rate of laser trabeculoplasty procedures provided by ophthalmologists who do
      not perform incisional glaucoma surgery increased 19.3% annually (P < .0001),
      while growth among glaucoma surgeons was more modest (annual growth of 9.2% [P =
      .0002]). CONCLUSIONS: While subspecialization is a growing reality in most areas
      of medicine, we found that the provision of clinic-based glaucoma care remains
      dependent on ophthalmologists who do not perform incisional glaucoma surgery.
      With increasing focus on integrated care, these findings will have important
      implications for residency education programs and their accrediting bodies and
      will inform decisions of health care policymakers, hospitals, and academic
      departments.

PMID- 24321472
TI  - DNA mismatch repair defects and microsatellite instability status in periocular
      sebaceous carcinoma.
AB  - PURPOSE: To characterize mismatch repair protein expression and the role of DNA
      repair abnormalities in sebaceous carcinomas of the ocular adnexa. DESIGN:
      Retrospective case-series study. METHODS: We reviewed 10 cases of sporadic
      sebaceous carcinoma and 1 case involving a patient with a family history
      consistent with Muir-Torre syndrome. Immunohistochemistry was used to analyze the
      presence of 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) in these
      tumors. DNA was extracted from 7 of the larger tumors as well as from adjacent
      normal control tissue and microsatellite instability (MSI) analysis using 5
      highly sensitive mononucleotides and 2 pentanucleotides was performed. RESULTS:
      All 10 sporadic periocular sebaceous carcinomas maintained strong staining of the
      4 mismatch repair genes, while tumor from the patient with Muir-Torre syndrome
      showed loss of staining for the mismatch repair genes MSH2 and MSH6. MSI testing
      of 7 tumors identified no changes in sporadic cases and yielded results
      supporting presence of repeat sequence instability in the Muir-Torre-associated
      case. CONCLUSIONS: Sporadic sebaceous carcinoma of the ocular adnexa is not
      commonly associated with a loss of mismatch repair genes or microsatellite
      instability.

PMID- 24321473
TI  - HLA-DR, DQ class II DNA typing in pediatric panuveitis and tubulointerstitial
      nephritis and uveitis.
AB  - PURPOSE: To describe chorioretinal lesions in pediatric uveitis that are
      associated strongly with the HLA-DR, DQ class II type associated with
      tubulointerstitial nephritis and uveitis (TINU). DESIGN: Retrospective,
      observational case series. METHODS:  SETTING: University-based clinic. PATIENT
      POPULATION: Fifteen consecutive patients with onset of bilateral panuveitis at
      less than 16 years of age who were seen between September 2004 and October 2012
      and 6 pediatric patients with confirmed TINU. OBSERVATION PROCEDURE: HLA-DR, DQ
      class II DNA typing. MAIN OUTCOME MEASURE: Detection of the HLA-DRB1*01 and HLA
      DQB1*05 risk alleles for TINU. RESULTS: Fourteen (93%) of the 15 patients with
      otherwise unexplained pediatric panuveitis typed HLA-DRB1*01-HLA-DQB1*05. Eleven
      (73.3%) of 15 patients had bilateral sharply demarcated, usually inferior, 200-
      to 300-MUm spots of chorioretinal atrophy, and 4 (27.7%) of 15 patients had
      bilateral clusters of 500- to 750-MUm poorly defined orange choroidal lesions
      without overlying atrophy of the retinal pigment epithelium. None had
      interstitial nephritis. Four of the 6 definite TINU cases had class II typing and
      TINU risk alleles; all 6 had bilateral panuveitis. The frequency of risk alleles
      was statistically higher in those with pediatric panuveitis than in the North
      American population and in nonpanuveitis pediatric uveitis patients assumed to
      have the North American HLA distribution (P < .0001, Fischer exact test).
      Positive likelihood ratios were 9.92 to 5.18, depending on assumptions regarding
      pretest probability of disease. CONCLUSIONS: Recognition of characteristic
      chorioretinal lesions in otherwise unexplained pediatric panuveitis, supported by
      selective HLA class II DNA typing, is useful in narrowing diagnostic
      possibilities and directing further evaluations. Panuveitis is underappreciated
      as a manifestation of TINU.

PMID- 24321474
TI  - Corneal cross-linking: intrastromal riboflavin concentration in iontophoresis
      assisted imbibition versus traditional and transepithelial techniques.
AB  - PURPOSE: To determine differences in riboflavin concentration in the anterior,
      intermediate, and posterior stroma after 3 corneal cross-linking imbibition
      techniques (standard epithelial [epi]-off, epi-on, and iontophoresis-assisted
      administration) of 0.1% riboflavin. DESIGN: Experimental laboratory investigation
      of human cadaver corneas not suitable for transplantation. METHODS: Ten corneas
      underwent imbibition with epi-on (n = 3), epi-off (n = 3), iontophoresis (n = 3),
      and saline exposure (control; n = 1). Femtosecond laser was used to produce 3 8
      mm discs of the superficial (0-150 MUm), intermediate (150-300 MUm), and deep
      stroma (>300 MUm). Riboflavin concentration was measured with high-performance
      liquid chromatography. The main outcome measure was riboflavin concentration at
      the 3 evaluated depths. RESULTS: The overall stromal concentration of riboflavin
      was 34.1 +/- 7.1 MUg/g in epi-off, 7.2 +/- 3.7 MUg/g in epi-on, and 15.0 +/- 5.1
      MUg/g in iontophoresis. The mean riboflavin content in the superficial slice in
      the epi-off group was about 2-fold greater than that of the iontophoresis group
      (50.5 +/- 5.3 MUg/g and 23.6 +/- 2.5 MUg/g, respectively) and 4-fold greater than
      that of the epi-on group (11.7 +/- 3.3 MUg/g). Similar differences among the 3
      groups were observed for the intermediate and posterior stromal slices,
      presenting an evident reduction of riboflavin concentration with increasing depth
      in all groups. Slice depth-dependent decrease in riboflavin concentration was
      statistically significant (general linear model (GLM); F1,6 = 62.265, P < .001),
      as was the group-dependent variation (GLM; F2,6 = 20.268, P = .002) and the slice
      depth group interaction (GLM; F2,6 = 18.004, P = .002). CONCLUSIONS: Corneal
      cross-linking transepithelial iontophoresis imbibition yielded greater and deeper
      riboflavin saturation with respect to conventional epi-on, while maintaining the
      advantages of avoiding epithelial removal and shorter procedure time, but did not
      reach concentrations obtained with standard epi-off.

PMID- 24321475
TI  - Comparison of wide-field fluorescein angiography and 9-field montage angiography
      in uveitis.
AB  - PURPOSE: To compare qualitatively and quantitatively Optos fundus camera
      fluorescein angiographic images of retinal vascular leakage with 9-field montage
      Topcon fluorescein angiography (FA) images in patients with uveitis. We
      hypothesized that Optos images reveal more leakage in patients with uveitis.
      DESIGN: Retrospective, observational case series. METHODS: Images of all patients
      with uveitis imaged with same-sitting Optos FA and 9-field montage FA during a 9
      month period at a single institution (52 eyes of 31 patients) were graded for the
      total area of retinal vascular leakage. The main outcome measure was area of
      fluorescein leakage. RESULTS: The area of apparent FA leakage was greater in
      Optos images than in 9-field montage images (median 22.5 mm(2) vs 4.8 mm(2), P <
      0.0001). Of the 49 (45%) eyes with gradable photos, 22 had at least 25% more
      leakage in the Optos image than in the montage image; 2 (4.1%) had at least 25%
      less leakage in Optos; and 25 (51%) were similar in the 2 modalities. There were
      2 eyes that had no apparent retinal vascular leakage in 9-field montage but were
      found to have apparent leakage in Optos images. Of the 49 eyes, 23 had posterior
      pole leakage, and of these, 17 (73.9%) showed more posterior pole leakage in the
      Optos image. A single 200-degree Optos FA image captured a mean 1.50* the area
      captured by montage photography. CONCLUSIONS: More retinal vascular pathology, in
      both the periphery and the posterior pole, is seen with Optos FA in patients with
      uveitis when compared with 9-field montage. The clinical implications of Optos FA
      findings have yet to be determined.

PMID- 24321476
TI  - Comparison of refractive stability after non-toric versus toric intraocular lens
      implantation during cataract surgery.
AB  - PURPOSE: To compare refractive state changes in eyes implanted with toric
      intraocular lenses (IOLs) vs non-toric IOLs, after cataract extraction. DESIGN:
      Retrospective, comparative. METHODS: In a single institution, 121 eyes underwent
      phacoemulsification and implantation with either non-toric IOLs or toric IOLs.
      The spherical value, cylindrical value, spherical equivalent (SE) of refractive
      error, and visual acuity were measured preoperatively and 1, 3, and 6 months
      after surgery. Main outcome measures were the pattern of changes of spherical,
      cylindrical, and SE values based on postoperative time, between different IOL
      types. RESULTS: The groups, which included patients who underwent surgery with
      SN60WF (Group I), SA6AT3 (Group II-3), SA6AT4 (Group II-4), and SA6AT5 lenses
      (Group II-5), contained 37, 29, 23, and 32 eyes, respectively. The cylindrical
      value was significantly decreased in all groups (P < .05). Before surgery, the SE
      of refractive errors was estimated as -0.21, -0.10, -0.20, and -0.22 in the
      respective groups. The actual remaining SE values were -0.19, -0.24, -0.42, and 
      0.56 at 1 month; -0.17, -0.26, -0.57, and -0.64 at 3 months; and -0.17, -0.26, 
      0.70, and -0.74 at 6 months postoperatively, respectively. The follow-up SE
      values in groups I and II-3 were similar (P > .05 in both groups); however,
      significant myopic changes were observed in Groups II-4 and II-5 after surgery,
      vs Group I (P < .05). CONCLUSION: Selection of toric IOLs for cataract surgery
      requires a refined formula to precisely determine necessary IOL power, especially
      in cases with high levels of astigmatism, to reliably and accurately prevent
      myopic outcomes.

PMID- 24321477
TI  - Neurophobia among medical students and non-specialist doctors in Sri Lanka.
AB  - BACKGROUND: Neurophobia is the fear of neurosciences held by medical students and
      doctors. The present study aims to identify whether Neurology is considered a
      difficult subject by medical students and non-specialist doctors from Sri Lanka
      and evaluate reasons for such perceived difficulties. METHODS: The study was
      conducted from May-June 2008. One hundred non-specialist doctors from the Colombo
      South Teaching Hospital and 150 medical students from the University of Sri
      Jayewardenepura were invited for the study. Data were collected by a pre-tested
      expert-validated self-administered questionnaire, designed to assess the degree
      of perceived difficulty, confidence, interest and knowledge of Neurology as
      compared to other subjects. It also evaluated reasons and probable strategies to
      overcome the perceived difficulties and/or lack of interests. RESULTS: All non
      specialist doctors and 148 medical students responded to the questionnaire
      (response rate-99.2%). The most favourite subject among medical students and non
      specialist doctors were Cardiology and Endocrinology respectively, while
      Neurology was ranked third. In all participants the current level of interest was
      most for Cardiology (3.52+/-1.36), while Neurology was the least interesting
      specialty for majority of medical students (18.5%) and non-specialist doctors
      (25.0%). The current level of knowledge among medical students was most for
      Cardiology (3.12+/-0.86), while Neurology (2.53+/-0.96) was ranked fifth. The
      most difficult specialty for majority of medical students (50.0%) and non
      specialist doctors (41.7%) was Neurology. All the participants were least
      confident when dealing with patients with headache (2.20+/-0.81), numbness of
      feet (2.07+/-0.79) and dizziness (2.07+/-0.78) when compared to dealing with
      other non-neurological complaints. The commonest reasons 'why Neurology was felt
      to be a difficult subject' were; the need to know basic neuro-anatomy and having
      a complex clinical examination. Participants' felt that clinical/hospital based
      teaching (3.49+/-0.65), case discussions (3.45+/-0.68) and teaching aids (3.10+/
      0.89) would be the most important teaching strategies to improve their competency
      in Neurology. CONCLUSION: Neurology is considered a difficult subject by
      undergraduates and non-specialist doctors of Sri Lanka. The main reason for the
      perceived difficulty was the lack of understanding of basic sciences and
      deficiencies in clinical teaching. This lack of confidence could have a
      significant impact on patient care.

PMID- 24321478
TI  - Genetic variation in GABRB3 is associated with Asperger syndrome and multiple
      endophenotypes relevant to autism.
AB  - BACKGROUND: Autism spectrum conditions (ASC) are associated with deficits in
      social interaction and communication, alongside repetitive, restricted, and
      stereotyped behavior. ASC is highly heritable. The gamma-aminobutyric acid (GABA)
      ergic system has been associated consistently with atypicalities in autism, in
      both genetic association and expression studies. A key component of the GABA
      ergic system is encoded by the GABRB3 gene, which has been previously implicated
      both in ASC and in individual differences in empathy. METHODS: In this study, 45
      genotyped single nucleotide polymorphisms (SNPs) within GABRB3 were tested for
      association with Asperger syndrome (AS), and related quantitative traits measured
      through the following tests: the Empathy Quotient (EQ), the Autism Spectrum
      Quotient (AQ), the Systemizing Quotient-Revised (SQ-R), the Embedded Figures Test
      (EFT), the Reading the Mind in the Eyes Test (RMET), and the Mental Rotation Test
      (MRT). Two-loci, three-loci, four-loci haplotype analyses, and one seven-loci
      haplotype analysis were also performed in the AS case-control sample. RESULTS:
      Three SNPs (rs7180158, rs7165604, rs12593579) were significantly associated with
      AS, and two SNPs (rs9806546, rs11636966) were significantly associated with EQ.
      Two SNP-SNP pairs, rs12438141-rs1035751 and rs12438141-rs7179514, showed
      significant association with variation in the EFT scores. One SNP-SNP pair,
      rs7174437-rs1863455, was significantly associated with variation in the MRT
      scores. Additionally, a few haplotypes, including a 19 kb genomic region that
      formed a linkage disequilibrium (LD) block in our sample and contained several
      nominally significant SNPs, were found to be significantly associated with AS.
      CONCLUSION: The current study confirms the role of GABRB3 as an important
      candidate gene in both ASC and normative variation in related endophenotypes.

PMID- 24321479
TI  - Simultaneous bilateral knee arthroplasty in octogenarians: can it be safe and
      effective?
AB  - Simultaneous bilateral knee arthroplasty (SBTKA) in octogenarians is
      controversial. Our purpose was to review the outcomes of octogenarians undergoing
      SBTKA. All patients greater than 80 years of age who underwent SBTKA by a single
      surgeon were retrospectively evaluated. Fifty-six patients with an average age of
      82.5 years were identified. Twelve postoperative complications occurred. Three
      were serious; two non-fatal PEs and one wound debridement. Minor complications
      included UTI, decubitus ulcer, DVT, confusion, transfusion reaction and ileus.
      Average postoperative survival was 7.4 years. No deaths occurred within 30 days
      postoperatively. Simultaneous bilateral total knee arthroplasty can be a safe and
      effective option for octogenarians. Complications and mortality are not higher
      for SBTKA compared to UTKA in this population.

PMID- 24321480
TI  - Powerful tumor cell growth-inhibiting activity of a synthetic derivative of
      atractyligenin: involvement of PI3K/Akt pathway and thioredoxin system.
AB  - BACKGROUND: The semi-synthetic ent-kaurane 15-ketoatractyligenin methyl ester
      (SC2017) has been previously reported to possess high antiproliferative activity
      against several solid tumor-derived cell lines. Our study was aimed at
      investigating SC2017 tumor growth-inhibiting activity and the underlying
      mechanisms in Jurkat cells (T-cell leukemia) and xenograft tumor models. METHODS:
      Cell viability was evaluated by MTT assay. Cell cycle progression, reactive
      oxygen species (ROS) elevation and apoptotic hallmarks were monitored by flow
      cytometry. Inhibition of thioredoxin reductase (TrxR) by biochemical assays.
      Levels and/or activation status of signaling proteins were assessed by western
      blotting. Xenograft tumors were generated with HCT 116 colon carcinoma cells.
      RESULTS: SC2017 displayed cell growth-inhibiting activity against Jurkat cells
      (half maximal inhibitory concentration values (IC50)<2MUM), but low cell-killing
      potential in human peripheral blood mononuclear cells (PBMC). The primary
      response of Jurkat cells to SC2017 was an arrest in G2 phase followed by caspase
      dependent apoptosis. Inhibition of PI3K/Akt pathway and TrxR activity by SC2017
      was demonstrated by biochemical and pharmacological approaches. At least, SC2017
      was found to inhibit xenograft tumor growth. CONCLUSIONS: Our results demonstrate
      that SC2017 inhibits tumor cell growth in in vitro and in vivo models, but
      displays moderate toxicity against PBMC. We also demonstrate that SC2017 promotes
      caspase-dependent apoptosis in Jurkat cells by affecting Akt activation status
      and TrxR functionality. GENERAL SIGNIFICANCE: Our observations suggest the semi
      synthetic ent-kaurane SC2017 as a promising chemotherapeutic compound. SC2017
      has, indeed, shown to possess tumor growth inhibiting activity and be able to
      counteract PI3K/Akt and Trx system survival signaling.

PMID- 24321481
TI  - Reply: To PMID 24321482.

PMID- 24321482
TI  - Editorial comment.

PMID- 24321483
TI  - Use of antegrade reverse-thermosensitive polymer during percutaneous
      nephrolithotomy to prevent fragment migration: initial experience.
AB  - INTRODUCTION: Our objective was to evaluate the feasibility and initial
      performance of Backstop reverse thermosensitive polymer to prevent antegrade
      stone fragment migration during percutaneous nephrolithotomy. TECHNICAL
      CONSIDERATIONS: Backstop was used during 5 percutaneous nephrolithotomy
      procedures to prevent stone migration into the ureter. Backstop was placed into
      the upper ureter under direct vision with a flexible nephroscope or with
      fluoroscopic guidance. Ultrasonic lithotripsy was then performed. Each patient
      was evaluated for the following: stone-free rate (postoperative computed
      tomography), rate of antegrade fragment migration, need for subsequent
      procedures, and complication rate. The average stone burden was 806 mm(2).
      Backstop was successfully deployed in all cases. Average procedure length was 106
      minutes. Three patients were rendered stone free, 1 patient retained 2 1-mm
      fragments in the kidney, and 1 patient retained multiple fragments in the kidney,
      distal ureter, and bladder, all of which were <3 mm. No patient required a
      secondary procedure, and there were no adverse events. CONCLUSION: Backstop
      appears to be feasible, safe, and easy to use. Backstop should be administered
      every 45 minutes for longer cases, and warm saline should be used during the case
      to prevent dissolution. A randomized controlled trial with a larger study
      population is needed to further evaluate these initial findings.

PMID- 24321484
TI  - Percutaneous microwave ablation of renal cell carcinoma is safe in patients with
      a solitary kidney.
AB  - OBJECTIVE: To present the results of clinical outcomes after microwave ablation
      (MWA) of renal cell carcinoma in patients with a solitary kidney without causing
      impairment to the uninvolved renal parenchyma and renal function. METHODS:
      Between 2006 and 2012, 14 solitary kidney patients with 16 tumors underwent
      percutaneous ultrasound-guided MWA at our institution. The tumor diameters ranged
      from 1.0 to 8.4 cm. The serum creatinine and urea levels of each patient before
      MWA, 1 day after MWA, and the most recent occasion on record at our institution
      were collected. Moreover, all the patients were followed up using contrast
      enhanced ultrasound and computed tomography or magnetic resonance imaging at 1,
      3, and 6 months and every 6 months thereafter. The technical success, survival
      rates, and complications were accessed. Patients were available for clinical and
      laboratory evaluations at a median follow-up time of 9.5 months (range, 1-56.4).
      RESULTS: Complete ablation was achieved in 15 of 16 (93.8%) lesions after 1 or 2
      MWA sessions; however, 2 of 14 (14.3%) patients died of widespread metastasis.
      The renal function was essentially preserved, and no patients require dialysis.
      No major complications were observed. CONCLUSION: MWA is a safe and effective
      treatment option for patients with a solitary kidney who suffer from inoperable
      renal cell carcinoma. The complication rate is low, and excellent tumor control
      can be achieved without deterioration of the residual renal function.

PMID- 24321486
TI  - Reinvestigation of growth of 'L-valine zinc sulphate' crystal.
AB  - A reinvestigation of the growth of l-valine zinc sulphate crystal is reported.
      The slow evaporation of an aqueous solution containing l-valine and zinc sulphate
      heptahydrate results in the fractional crystallization of l-valine and not the
      organic inorganic hybrid nonlinear optical l-valine zinc sulphate crystal, as
      reported by Puhal Raj and Ramachandra Raja (2012). 

PMID- 24321485
TI  - In silico to in vivo splicing analysis using splicing code models.
AB  - With the growing appreciation of RNA splicing's role in gene regulation,
      development, and disease, researchers from diverse fields find themselves
      investigating exons of interest. Commonly, researchers are interested in knowing
      if an exon is alternatively spliced, if it is differentially included in specific
      tissues or in developmental stages, and what regulatory elements control its
      inclusion. An important step towards the ability to perform such analysis in
      silico was made with the development of computational splicing code models. Aimed
      as a practical how-to guide, we demonstrate how researchers can now use these
      code models to analyze a gene of interest, focusing on Bin1 as a case study.
      Bridging integrator 1 (BIN1) is a nucleocytoplasmic adaptor protein known to be
      functionally regulated through alternative splicing in a tissue-specific manner.
      Specific Bin1 isoforms have been associated with muscular diseases and cancers,
      making the study of its splicing regulation of wide interest. Using AVISPA, a
      recently released web tool based on splicing code models, we show that many Bin1
      tissue-dependent isoforms are correctly predicted, along with many of its known
      regulators. We review the best practices and constraints of using the tool,
      demonstrate how AVISPA is used to generate high confidence novel regulatory
      hypotheses, and experimentally validate predicted regulators of Bin1 alternative
      splicing. 

PMID- 24321487
TI  - [5th Meeting of the Francophone Society of Peripheral Nerves / 5th Days of the
      Francophone Society of Peripheral Nerves: Foreword].

PMID- 24321488
TI  - Size and pH effects of chitooligomers on antibacterial activity against
      Staphylococcus aureus.
AB  - The antimicrobial activity of chitooligomers (COSs) has attracted considerable
      interest but there are few reports on antibacterial activity of each individual
      COS. This study focuses on investigating the size and pH effects of COS on its
      antibacterial activity against Staphylococcus aureus. Minimum inhibitory
      concentrations (MICs) of five single COSs and five COS fractions with narrow
      degrees of polymerization (DP) were determined at different pH mediums. The
      results revealed that the antibacterial activity of COS required structural
      essential with a DP of at least 5 and the inhibitory effect increased with
      increasing DP. Lower pH value could enhance the antibacterial activity of COS.
      The COS with DP>12 showed a MIC value of 62.5mg/mL at pH 6.0, while the MIC value
      increased to 500 and 1000 mg/mL at pH 6.5 and 7.0, respectively. The cell
      membrane integrity assay and SEM suggested that the COS with high DP could cause
      bacteria clustering and further lysis of cell.

PMID- 24321489
TI  - Antioxidant and immunological activity in vitro of polysaccharides from Phellinus
      nigricans mycelia.
AB  - Three polysaccharide fractions, namely, PNMP 1, PNMP2, and PNMP3, were isolated
      from Phellinus nigricans mycelia. The average molecular weights of PNMP1, PNMP2,
      and PNMP3 were approximately 28.4, 31.5, and 26.1 kDa, respectively. PNMP2 and
      PNMP3 comprised six monosaccharides: arabinose, fucose, glucose, galactose,
      mannose, and xylose. PNMP1 comprised only four monosaccharides: glucose,
      galactose, mannose, and xylose. In vitro antioxidant tests showed that PNMP2 and
      PNMP3 significantly scavenged superoxide radical, hydroxyl radical, and 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical. PNMP1 effectively inhibited DPPH
      radical. Lymphocyte proliferation was significantly increased by PNMP1, PNMP2,
      and PNMP3, particularly by PNMP2 and PNMP3 in the presence of concanavalin A or
      lipopolysaccharide as mitogens for lymphocytes.

PMID- 24321490
TI  - A novel quaternized chitosan-melamine-glutaraldehyde resin for the removal of
      nitrate and phosphate anions.
AB  - A terpolymer of chitosan-melamine-glutaraldehyde was prepared for the first time
      and it was quaternized with glycidyl trimethyl ammonium chloride (GTMAC). The
      quaternized chitosan-melamine-glutaraldehyde resin (QCMGR) was found to be
      effective for the removal of nitrate and phosphate oxyanions. The resin was
      characterised with FTIR, SEM, EDAX, TGA, DTA, XRD and water regain property.
      Batch method was followed to optimise the conditions for the removal of nitrate
      and phosphate. Chemical kinetics of the adsorption was well fitted by pseudo
      second order and particle diffusion models and the adsorption process followed
      the Freundlich isotherm model well. The nitrate and phosphate adsorption capacity
      of QCMGR from 1000 mg/L respective solutions were 97.5 and 112.5mg/g,
      respectively. Nitrate and phosphate anions adsorbed effectively on QCMGR by
      replacing Cl(-) ions at the quaternary ammonium group by exchange mechanism. Even
      after 10th regeneration cycle the adsorbent fully retained its adsorption
      efficiency. Nitrate and phosphate removal efficiency of QCMGR was also tested by
      column method.

PMID- 24321491
TI  - Huaier polysaccharides suppresses hepatocarcinoma MHCC97-H cell metastasis via
      inactivation of EMT and AEG-1 pathway.
AB  - We have recently reported that astrocyte elevated gene-1 (AEG-1) might be an
      epithelial-mesenchymal transition (EMT) associated biomarker in human
      hepatocellular carcinoma (HCC), and play an important role in the progression of
      hepatocellular carcinoma. To extend our study, we examined here the anti-invasive
      and metastatic effects of Huaier polysaccharide (HP) on human HCC cell line
      MHCC97-H and explored its possible mechanism of action. Treatment with HP dose
      dependently inhibited the proliferation, adhesion, migration and invasion of
      MHCC97-H cells in vitro. This was achieved not only by reducing the expression of
      AEG-1 and N-cadherin, but also by enhancing E-cadherin expression. Therefore,
      these data suggested that HP can inhibit the growth and metastatic potential of
      MHCC97-H cells through modulation of the AEG-1/EMT pathway. 

PMID- 24321492
TI  - Crystal structure of PfbA, a surface adhesin of Streptococcus pneumoniae,
      provides hints into its interaction with fibronectin.
AB  - PfbA is a surface adhesin and invasin of Streptococcus pneumoniae that binds to
      human fibronectin and plasminogen of the host extracellular matrix. It is a
      virulence factor for its pathogenesis. The crystal structure of recombinant
      PfbA150-607 from S. pneumoniae strain R6, was determined using multiwavelength
      anomalous dispersion (MAD) method and refined to 1.90A resolution. The structure
      of rPfbA150-607 revealed that residues Thr150 to Lys570 form a rigid parallel
      beta helix, followed by a short disordered region (571-607) that consists of beta
      hairpins. The structural organization of the beta helix resembles that of
      polysaccharide-modifying enzymes. The structural and sequence features essential
      for fibronectin-binding observed in the well characterized fibronectin-binding
      proteins such as FnBPA of Staphylococcus aureus, SfbI of Streptococcus pyogenes
      and BBK32 of Borrelia burgdorferi has been found in rPfbA150-607. Based on this,
      it is predicted that the disordered region following the beta helix could be the
      fibronectin-binding region in PfbA. PfbA150-607 contains relatively high number
      of surface exposed lysines and these residues are probably involved in binding
      plasmin(ogen) as observed in other plasminogen-binding proteins. 

PMID- 24321493
TI  - Construction and implementation of a TDCR system at ENEA.
AB  - A new 4pi (LS) TDCR system was built at ENEA-INMRI. Three photomultiplier tubes,
      arranged in a planar 120 degrees  geometry around a spherical optical chamber,
      were directly linked to a CAEN Desktop Digitizer DT5720. This module, based on
      the Field Programmable Gate Array (FPGA) technology for real time Digital Pulse
      Processing (DPP), allowed to replace all the classical TDCR electronics by only
      one device. The activity of (3)H and (63)Ni standard sources were successfully
      measured by the new detector. 

PMID- 24321494
TI  - Update of NIST half-life results corrected for ionization chamber source-holder
      instability.
AB  - As reported at the ICRM 2011, it was discovered that the source holder used for
      calibrations in the NIST 4pigamma ionization chamber (IC) was not stable. This
      has affected a large number of half-life measurement results previously reported
      and used in compilations of nuclear data. Corrections have been made on all of
      the half-life data based on the assumption that the changes to the ionization
      chamber response were gradual. The corrections are energy dependent and therefore
      radionuclide specific. This presentation will review our results and present the
      recommended changes in half-life values and/or uncertainties. 

PMID- 24321495
TI  - Development of a transfer standard for the measurement of low Rn-222 activity
      concentration in air.
AB  - A large volume transfer standard has been developed to calibrate commercial radon
      measurement devices in a homogeneous Rn-222 reference atmosphere. The transfer
      standard serves for the realization, maintenance and dissemination of the unit
      Bq/m(3) below 1 kBq/m(3). The transfer standard consists of a multi-wire impulse
      ionization chamber, electronic measurement equipment and the corresponding
      software. The multi-wire impulse ionization chamber is composed of two parallel
      printed boards. Between the boards, 478 vertical electrode wires are soldered in
      to include a volume of 10 L. In the dependency of the energy, the alpha-particles
      of Rn-222 and the decay products are detected in the active volume of the multi
      wire impulse ionization chamber. By means of the measurement software an alpha
      energy spectrum is produced. Via different algorithms, the activity concentration
      of the Rn-222 reference atmosphere is determined.

PMID- 24321496
TI  - Radon leakage as a source of additional uncertainty in simultaneous determination
      of 226Ra and 228Ra by gamma spectrometry--validation of analysis procedure.
AB  - A series of validation experiments was carried out to assess robustness,
      repeatability, and trueness of an analysis procedure for simultaneous
      determination of (226)Ra and (228)Ra in water samples. The study revealed
      instabilities in the radon holding capacity of the sample matrix (epoxy resin).
      The discovered effect is a new additional component in the uncertainty budget
      which should be considered when (226)Ra is measured via its progeny in similar
      sample matrices. 

PMID- 24321497
TI  - The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are
      unmasked by loss of p53 in murine embryonic fibroblasts.
AB  - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is characterized by the
      presence of a fusion protein EWS/WT1, arising from the t (11;22) (p13;q12)
      translocation. Here we examine the oncogenic properties of two splice variants of
      EWS/WT1, EWS/WT1-KTS and EWS/WT1 + KTS. METHODS: We over-expressed both EWS/WT1
      variants in murine embryonic fibroblasts (MEFs) of wild-type, p53+/- and p53-/-
      backgrounds and measured effects on cell-proliferation, anchorage-independent
      growth, clonogenicity after serum withdrawal, and sensitivity to cytotoxic drugs
      and gamma irradiation in comparison to control cells. We examined gene expression
      profiles in cells expressing EWS/WT1. Finally we validated our key findings in a
      small series of DSRCT. RESULTS: Neither isoform of EWS/WT1 was sufficient to
      transform wild-type MEFs however the oncogenic potential of both was unmasked by
      p53 loss. Expression of EWS/WT1 in MEFs lacking at least one allele of p53
      enhanced cell-proliferation, clonogenic survival and anchorage-independent
      growth. EWS/WT1 expression in wild-type MEFs conferred resistance to cell-cycle
      arrest after irradiation and daunorubicin induced apoptosis. We show DSRCT
      commonly have nuclear localization of p53, and copy-number amplification of
      MDM2/MDMX. Expression of either isoform of EWS/WT1 induced characteristic mRNA
      expression profiles. Gene-set enrichment analysis demonstrated enrichment of WNT
      pathway signatures in MEFs expressing EWS/WT1 + KTS. Wnt-activation was validated
      in cell lines with over-expression of EWS/WT1 and in DSRCT. CONCLUSION: In
      conclusion, we show both isoforms of EWS/WT1 have oncogenic potential in MEFs
      with loss of p53. In addition we provide the first link between EWS/WT1 and Wnt
      pathway signaling. These data provide novel insights into the function of the
      EWS/WT1 fusion protein which characterize DSRCT.

PMID- 24321499
TI  - Bone disease in systemic sclerosis: outcomes and associations.
AB  - OBJECTIVES: The relationship between systemic sclerosis (SSc) and low bone
      mineral density (BMD) is poorly understood. The aim of this study is to improve
      our understanding of low bone density in SSc and its potential consequences.
      METHODS: Fifty consecutive unselected SSc patients were approached. Demographics,
      disease manifestations, BMD (lumbar spine and femoral neck) were collected at
      baseline and occurrence of fracture and death were collected over 2 years. The 10
      year risk of osteoporotic fracture was estimated using the fracture risk
      assessment tool (FRAX) v2.0 with the Canadian population reference. Fisher's
      Exact and Student's t-tests were used to evaluate differences between patients
      with and without low BMD. Logistic regression was used for multivariate analysis.
      RESULTS: Forty-five patients had complete BMD data. Twenty-eight patients (62%)
      had low BMD, of those 10 (36%) had osteoporosis. There was no difference in age,
      sex, or disease duration between both groups. Low BMD was associated with non
      Caucasian race (57% vs. 18%, p=0.01), postmenopausal status (83% vs. 47%,
      p<0.01), low body mass index (24.5 vs. 26.2, p=0.05). The mean 10-year risk of
      developing a major osteoporotic fracture and a femoral neck fracture was higher
      in the low BMD group (10.2% vs. 4.8%, p=0.12) and (4.1% vs. 0.5%, p = 0.16)
      respectively. Fourteen percent (4/28) of SSc patients with low BMD had a
      fracture, compared to 6% (1/17) SSc patients without low BMD. Fracture-related
      mortality did not occur in any patients. CONCLUSIONS: Low BMD and fracture are
      frequently seen in SSc patients. A number of clinically relevant factors are
      associated with low BMD. Further research is needed to evaluate these factors and
      the role of bone-specific treatments in SSc.

PMID- 24321498
TI  - Toll-like receptor signaling adapter proteins govern spread of neuropathic pain
      and recovery following nerve injury in male mice.
AB  - BACKGROUND: Spinal Toll-like receptors (TLRs) and signaling intermediaries have
      been implicated in persistent pain states. We examined the roles of two major TLR
      signaling pathways and selected TLRs in a mononeuropathic allodynia. METHODS: L5
      spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and
      female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2,
      Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4
      /- female mice. We examined tactile allodynia using von Frey hairs. Iba-1
      (microglia) and GFAP (astrocytes) were assessed in spinal cords by
      immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the
      Bonferroni post hoc test was used. RESULTS: In WT male and female mice, SNL
      lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In
      males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly,
      but incompletely, reversed (approximately 50%) as compared to WT. This effect was
      not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP
      were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF,
      showed an approximately 50% reduction in withdrawal thresholds and reduced
      ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed
      a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of
      the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the
      TRIF-signaling deficient mice as compared to WT, but no significant increase in
      GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling
      deficient mice. Conversely, IFNbeta, released downstream to TRIF signaling,
      administered intrathecally, temporarily reversed the tactile allodynia.
      CONCLUSIONS: These observations suggest a critical role for the MyD88 pathway in
      initiating neuropathic pain, but a distinct role for the TRIF pathway and
      interferon in regulating neuropathic pain phenotypes in male mice.

PMID- 24321500
TI  - Childhood cancers: what is a possible role of infectious agents?
AB  - The etiology of childhood cancers has been studied for more than 40 years.
      However, most if not all cancers occurring in children are attributed to unknown
      causes. This review is focused on the role of infections in cancer development
      and progression in children. The main infectious agents include human
      herpesviruses, polyoma viruses, and human papilloma viruses. It is known that
      infections can lead to carcinogenesis through various mechanisms, and most likely
      act in addition to genetic and environmental factors. Given the importance of the
      infectious etiology of childhood cancers, clinical implications and possible
      prevention strategies are discussed. 

PMID- 24321501
TI  - Selective serotonin reuptake inhibitors in human pregnancy: on the way to
      resolving the controversy.
AB  - There has been an increase in the use of selective serotonin reuptake inhibitors
      (SSRIs) during pregnancy. However, in the last 10 years, in spite of a vast
      literature regarding use in pregnancy there seems to be some confusion as to the
      possible risk of these drugs, especially related to cardiovascular anomalies. In
      addition, there are data on developmental follow-up studies that raise the
      question of possible slight developmental and neurobehavioral problems. The
      purpose of the present review is therefore to critically summarize the current
      evidence for the risk/benefit analysis of SSRI use in human pregnancy. Although
      most studies have not shown an increase in the overall risk of major
      malformations, several have suggested that the use of SSRIs may be associated
      with a small increased risk for cardiovascular malformations. However, new
      compelling evidence shows that this apparent increased risk occurs also in women
      with untreated depression, highlighting the probable ascertainment bias involved
      in many of these studies. Persistent pulmonary hypertension of the newborn (PPHN)
      has also been described with an absolute risk of <1%; however, here too, higher
      rates were described among offspring of women with untreated depression. Poor
      neonatal adaptation has been described in up to 30% of neonates exposed to SSRIs
      late in pregnancy. Of the few postnatal developmental follow-up studies, there
      are no significant developmental problems. The literature on SSRIs in pregnancy
      is somewhat confusing but when analysing all prospective cohort data there seems
      to be no demonstrable increase in the rate of major anomalies or developmental
      disorders. When evaluating the risk/benefit ratio of SSRI treatment in pregnancy,
      the risk associated with treatment discontinuation - e.g. higher frequency of
      relapse, increased risk of preterm delivery and postpartum depression - appear to
      outweigh the potential, unproven risks of treatment. Moreover, maternal
      depression may negatively affect the child's development, emphasizing the
      importance of prevention by appropriate treatment during pregnancy with the least
      minimal effective dose. 

PMID- 24321502
TI  - EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and
      castration-resistant prostate cancer.
AB  - OBJECTIVE: To present a summary of the 2013 version of the European Association
      of Urology (EAU) guidelines on the treatment of advanced, relapsing, and
      castration-resistant prostate cancer (CRPC). EVIDENCE ACQUISITION: The working
      panel performed a literature review of the new data (2011-2013). The guidelines
      were updated, and levels of evidence and/or grades of recommendation were added
      to the text based on a systematic review of the literature that included a search
      of online databases and bibliographic reviews. EVIDENCE SYNTHESIS: Luteinising
      hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic
      prostate cancer (PCa). LHRH antagonists decrease testosterone without any
      testosterone surge, and they may be associated with an oncologic benefit compared
      with LHRH analogues. Complete androgen blockade has a small survival benefit of
      about 5%. Intermittent androgen deprivation results in noninferior oncologic
      efficacy when compared with continuous androgen-deprivation therapy (ADT) in well
      selected populations. In locally advanced and metastatic PCa, early ADT does not
      result in a significant survival advantage when compared with delayed ADT.
      Relapse after local therapy is defined by prostate-specific antigen (PSA) values
      >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and
      after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage
      RT (SRT) at PSA levels <0.5 ng/ml and SRP or cryosurgical ablation of the
      prostate in radiation failures. Endorectal magnetic resonance imaging and 11C
      choline positron emission tomography/computed tomography (PET/CT) are of limited
      importance if the PSA is <1.0 ng/ml; bone scans and CT can be omitted unless PSA
      is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone
      levels, and screening for cardiovascular disease and metabolic syndrome.
      Treatment of CRPC includes sipuleucel-T, abiraterone acetate plus prednisone
      (AA/P), or chemotherapy with docetaxel at 75mg/m(2) every 3 wk. Cabazitaxel,
      AA/P, enzalutamide, and radium-223 are available for second-line treatment of
      CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with
      CRPC and osseous metastases to prevent skeletal-related complications.
      CONCLUSIONS: The knowledge in the field of advanced, metastatic, and castration
      resistant PCa is rapidly changing. These EAU guidelines on PCa summarise the most
      recent findings and put them into clinical practice. A full version is available
      at the EAU office or at www.uroweb.org. PATIENT SUMMARY: We present a summary of
      the 2013 version of the European Association of Urology guidelines on treatment
      of advanced, relapsing, and castration-resistant prostate cancer (CRPC).
      Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in
      metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without
      any testosterone surge, and they might be associated with an oncologic benefit
      compared with LHRH analogues. Complete androgen blockade has a small survival
      benefit of about 5%. Intermittent androgen deprivation results in noninferior
      oncologic efficacy when compared with continuous androgen-deprivation therapy
      (ADT) in well-selected populations. In locally advanced and metastatic PCa, early
      ADT does not result in a significant survival advantage when compared with
      delayed ADT. Relapse after local therapy is defined by prostate-specific antigen
      (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above
      the nadir and after radiation therapy. Therapy for PSA relapse after RP includes
      salvage radiation therapy at PSA levels <0.5 ng/ml and salvage RP or cryosurgical
      ablation of the prostate in radiation failures. Multiparametric magnetic
      resonance imaging and 11C-choline positron emission tomography/computed
      tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone
      scans, and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should
      include analysis of PSA and testosterone levels, and screening for cardiovascular
      disease and metabolic syndrome. Treatment of castration-resistant CRPC includes
      sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with
      docetaxel 75 mg/m(2) every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223
      are available for second-line treatment of CRPC following docetaxel. Zoledronic
      acid and denosumab can be used in men with CRPC and osseous metastases to prevent
      skeletal-related complications. The guidelines reported should be adhered to in
      daily routine to improve the quality of care in PCa patients. As we have shown
      recently, guideline compliance is only in the area of 30-40%.

PMID- 24321503
TI  - How psychotherapists handle treatment errors -- an ethical analysis.
AB  - BACKGROUND: Dealing with errors in psychotherapy is challenging, both ethically
      and practically. There is almost no empirical research on this topic. We aimed
      (1) to explore psychotherapists' self-reported ways of dealing with an error made
      by themselves or by colleagues, and (2) to reconstruct their reasoning according
      to the two principle-based ethical approaches that are dominant in the ethics
      discourse of psychotherapy, Beauchamp & Childress (B&C) and Lindsay et al. (L).
      METHODS: We conducted 30 semi-structured interviews with 30 psychotherapists
      (physicians and non-physicians) and analysed the transcripts using qualitative
      content analysis. Answers were deductively categorized according to the two
      principle-based ethical approaches. RESULTS: Most psychotherapists reported that
      they preferred to an disclose error to the patient. They justified this by
      spontaneous intuitions and common values in psychotherapy, rarely using explicit
      ethical reasoning. The answers were attributed to the following categories with
      descending frequency: 1. Respect for patient autonomy (B&C; L), 2. Non
      maleficence (B&C) and Responsibility (L), 3. Integrity (L), 4. Competence (L) and
      Beneficence (B&C). CONCLUSIONS: Psychotherapists need specific ethical and
      communication training to complement and articulate their moral intuitions as a
      support when disclosing their errors to the patients. Principle-based ethical
      approaches seem to be useful for clarifying the reasons for disclosure. Further
      research should help to identify the most effective and acceptable ways of error
      disclosure in psychotherapy.

PMID- 24321504
TI  - pH sensitivity of chlorophyll fluorescence quenching is determined by the
      detergent/protein ratio and the state of LHCII aggregation.
AB  - Here we show how the protein environment in terms of detergent
      concentration/protein aggregation state, affects the sensitivity to pH of
      isolated, native LHCII, in terms of chlorophyll fluorescence quenching. Three
      detergent concentrations (200, 20 and 6MUM n-dodecyl beta-d-maltoside) have been
      tested. It was found that at the detergent concentration of 6MUM, low pH
      quenching of LHCII is close to the physiological response to lumen acidification
      possessing pK of 5.5. The analysis has been conducted both using arbitrary PAM
      fluorimetry measurements and chlorophyll fluorescence lifetime component
      analysis. The second led to the conclusion that the 3.5ns component lifetime
      corresponds to an unnatural state of LHCII, induced by the detergent used for
      solubilising the protein, whilst the 2ns component is rather the most
      representative lifetime component of the conformational state of LHCII in the
      natural thylakoid membrane environment when the non-photochemical quenching (NPQ)
      was absent. The 2ns component is related to a pre-aggregated LHCII that makes it
      more sensitive to pH than the trimeric LHCII with the dominating 3.5ns lifetime
      component. The pre-aggregated LHCII displayed both a faster response to protons
      and a shift in the pK for quenching to higher values, from 4.2 to 4.9. We
      concluded that environmental factors like lipids, zeaxanthin and PsbS protein
      that modulate NPQ in vivo could control the state of LHCII aggregation in the
      dark that makes it more or less sensitive to the lumen acidification. This
      article is part of a special issue entitled: photosynthesis research for
      sustainability: keys to produce clean energy.

PMID- 24321505
TI  - Characterization of the photosynthetic apparatus of the Eustigmatophycean
      Nannochloropsis gaditana: evidence of convergent evolution in the supramolecular
      organization of photosystem I.
AB  - Nannochloropsis gaditana belongs to Eustigmatophyceae, a class of eukaryotic
      algae resulting from a secondary endosymbiotic event. Species of this class have
      been poorly characterized thus far but are now raising increasing interest in the
      scientific community because of their possible application in biofuel production.
      Nannochloropsis species have a peculiar photosynthetic apparatus characterized by
      the presence of only chlorophyll a, with violaxanthin and vaucheriaxanthin esters
      as the most abundant carotenoids. In this study, the photosynthetic apparatus of
      this species was analyzed by purifying the thylakoids and isolating the different
      pigment-binding complexes upon mild solubilization. The results from the
      biochemical and spectroscopic characterization showed that the photosystem II
      antenna is loosely bound to the reaction center, whereas the association is
      stronger in photosystem I, with the antenna-reaction center super-complexes
      surviving purification. Such a supramolecular organization was found to be
      conserved in photosystem I from several other photosynthetic eukaryotes, even
      though these taxa are evolutionarily distant. A hypothesis on the possible
      selective advantage of different associations of the antenna complexes of
      photosystems I and II is discussed. 

PMID- 24321506
TI  - External loops at the ferredoxin-NADP(+) reductase protein-partner binding cavity
      contribute to substrates allocation.
AB  - Ferredoxin-NADP(+) reductase (FNR) is the structural prototype of a family of FAD
      containing reductases that catalyze electron transfer between low potential
      proteins and NAD(P)(+)/H, and that display a two-domain arrangement with an open
      cavity at their interface. The inner part of this cavity accommodates the
      reacting atoms during catalysis. Loops at its edge are highly conserved among
      plastidic FNRs, suggesting that they might contribute to both flavin
      stabilization and competent disposition of substrates. Here we pay attention to
      two of these loops in Anabaena FNR. The first is a sheet-loop-sheet motif,
      loop102-114, that allocates the FAD adenosine. It was thought to determine the
      extended FAD conformation, and, indirectly, to modulate isoalloxazine electronic
      properties, partners binding, catalytic efficiency and even coenzyme specificity.
      The second, loop261-269, contains key residues for the allocation of partners and
      coenzyme, including two glutamates, Glu267 and Glu268, proposed as candidates to
      facilitate the key displacement of the C-terminal tyrosine (Tyr303) from its
      stacking against the isoalloxazine ring during the catalytic cycle. Our data
      indicate that the main function of loop102-114 is to provide the inter-domain
      cavity with flexibility to accommodate protein partners and to guide the coenzyme
      to the catalytic site, while the extended conformation of FAD must be induced by
      other protein determinants. Glu267 and Glu268 appear to assist the conformational
      changes that occur in the loop261-269 during productive coenzyme binding, but
      their contribution to Tyr303 displacement is minor than expected. Additionally,
      loop261-269 appears a determinant to ensure reversibility in photosynthetic FNRs.

PMID- 24321507
TI  - Comparative effectiveness of senna to prevent problematic constipation in
      pediatric oncology patients receiving opioids: a multicenter study of clinically
      detailed administrative data.
AB  - CONTEXT: Pediatric oncology patients often receive prolonged courses of opioids,
      which can result in constipation. OBJECTIVES: Comparing patients who received
      senna matched with similar patients who received other oral bowel medications,
      determine the subsequent risk of "problematic constipation," assessed as the
      occurrence of the surrogate markers of receiving an enema, escalation of oral
      bowel medications, and abdominal radiographic imaging. METHODS: This was a
      retrospective cohort study of hospitalized pediatric oncology patients less than
      21 years of age in 78 children's and adult hospitals between 2006 and 2011 who
      were started on seven consecutive days or more of opioid therapy and were started
      on an oral bowel medication within the first two days of opioid therapy.
      Clinically detailed administrative data were used from the Pediatric Health
      Information System and the Premier Perspective Database. After performing
      propensity score matching of similar patients who started senna and who started a
      different oral bowel medication, Cox regression modeling was used to compare the
      subsequent hazard of the surrogate markers. RESULTS: The final matched sample of
      586 patients averaged 11.5 years of age (range 0-20 years); 41.8% (n = 245) had
      blood cancer, 50.3% (n = 295) had solid tumor cancer, and 7.9% (n = 46) had brain
      cancer. Initiating senna therapy within two days of starting the prolonged opioid
      course, compared with initiating another oral bowel medication, was significantly
      associated with a lower hazard during the ensuing five days for receipt of an
      enema (hazard ratio [HR], 0.31; 95% CI, 0.11-0.91) or undergoing abdominal
      radiographic imaging (HR, 0.74; 95% CI, 0.55-0.98), was marginally associated
      with a lower hazard of oral bowel medicine escalation (HR, 0.78; 95% CI, 0.59
      1.03), and overall was significantly associated with a lower hazard of the
      composite end point of problematic constipation (HR, 0.70; 95% CI, 0.56-0.88).
      CONCLUSION: Initiating senna therapy, compared with other oral bowel medications,
      diminishes the subsequent risk of surrogate markers of problematic constipation
      in this population.

PMID- 24321509
TI  - The bow tie model of 21st century palliative care.

PMID- 24321508
TI  - The influence of patients' quality of life at the end of life on bereaved
      caregivers' suicidal ideation.
AB  - CONTEXT: Recent studies have shown that patients' quality of life at the end of
      life (QOL@EOL) affects the psychosocial adjustment of bereaved family caregivers.
      OBJECTIVES: To examine the relationship between patients' QOL@EOL and the
      suicidal ideation of their surviving bereaved caregivers. METHODS: Data were
      derived from the Coping with Cancer (CwC1) Study, a U.S. National Cancer
      Institute-funded multicenter prospective cohort investigation of patients with
      advanced cancer and their caregivers, in which patients were enrolled September
      2002 to February 2008. CwC1 data were used to examine changes in suicidal
      ideation in family caregivers before and after the patient's death (N = 127).
      Caregiver baseline suicidal ideation was assessed using the Yale Evaluation of
      Suicidality (YES) Scale a median of 4.1 months pre-loss; caregivers' perception
      of patients' QOL@EOL was assessed a median of 1.9 months postloss; and caregiver
      suicidal ideation in bereavement was assessed using the YES a median of 6.5
      months postloss. Suicidal ideation was defined as a positive screen on the YES.
      We used multiple logistic regression analysis to examine the effect of
      caregivers' perceptions of patients' QOL@EOL on the suicidal ideation of bereaved
      caregiver's, adjusting for the caregiver's baseline suicidal ideation and
      confounding influences. RESULTS: Caregivers' perception of patients' QOL@EOL was
      significantly inversely related to caregivers' suicidal ideation postloss
      (adjusted odds ratio = 0.79, P = 0.023), after we adjusted for caregivers'
      baseline suicidal ideation, relationship to patient, and years of education.
      CONCLUSION: The more caregivers perceive their loved ones' QOL@EOL to be poor,
      the greater their risk for suicidal ideation in bereavement over and above prior
      levels of suicidal ideation. Caregivers of patients who have poor QOL@EOL appear
      to be a group of caregivers to target for reduction of suicidal risk.

PMID- 24321510
TI  - The impact of body mass index dynamics on survival of patients with advanced
      pancreatic cancer receiving chemotherapy.
AB  - CONTEXT: High body mass index (BMI) is linked to an increased risk of developing
      pancreatic cancer (PC). However, in patients with advanced PC (APC), especially
      those receiving palliative chemotherapy, the impact of BMI on survival has not
      been investigated fully. OBJECTIVES: To assess changes in BMI during the course
      of APC and their impact on patient survival, specifically for those receiving
      palliative chemotherapy. METHODS: Consecutive patients with APC, all of whom were
      treated with palliative chemotherapy, were enrolled during 2003-2010. Clinical
      characteristics and prognoses were analyzed. RESULTS: A total of 425 patients
      participated (median age, 60.1 years). At diagnosis of APC, patients' BMI
      distribution of patients was as follow: <18.5 (45, 10.6%); 18.5-19.9 (67, 15.8%);
      20.0-22.4 (156, 36.7%); 22.5-24.9 (107, 25.2%); 25.0-29.9 (49, 11.5%); and >=
      30.0 (1, 0.2%). Median overall survival (OS) was 8.1 months (95% confidence
      interval 7.2, 9.1). Precancer BMI and baseline BMI (at diagnosis) had no impact
      on OS. Weight loss at diagnosis (precancer weight minus weight at diagnosis) and
      weight loss during first-line chemotherapy (both stipulated as BMI change >= 1)
      were associated with shortened OS (hazard ratio, 1.300; P = 0.012 and hazard
      ratio, 1.367; P = 0.010, respectively). CONCLUSION: In patients with APC
      undergoing palliative chemotherapy, decreases in BMI at APC diagnosis and during
      chemotherapy are more hazardous for OS than precancer BMI or baseline BMI (at
      diagnosis) as absolute values. Further studies are needed to validate this
      finding and investigate strategies to maintain BMI during chemotherapy in this
      setting.

PMID- 24321513
TI  - RAADS-14 Screen: validity of a screening tool for autism spectrum disorder in an
      adult psychiatric population.
AB  - BACKGROUND: Autism spectrum disorder (ASD) can be difficult to distinguish from
      other psychiatric disorders. The clinical assessment of ASD is lengthy, and has
      to be performed by a specialized clinician. Therefore, a screening instrument to
      aid in the identification of patients who may have undiagnosed ASD should be
      useful. The purpose of this study was to develop such a screening instrument.
      METHODS: Based on the 80 item Ritvo Autism and Asperger Diagnostic Scale-Revised
      (RAADS-R), we developed a 14 item self-evaluation questionnaire, the RAADS-14
      Screen. In total, 135 adults with ASD and 508 psychiatric controls completed the
      abridged version of the RAADS-R. RESULTS: The RAADS-14 Screen score was
      significantly higher in the ASD group than in the control samples, with a median
      score of 32 for ASD, 15 for attention deficit hyperactivity disorder, and 11 for
      other psychiatric disorders (P < 0.001). A cut-off score of 14 or above reached a
      sensitivity of 97% and a specificity of 46 to 64%. A factor analysis identified
      three factors consistent with mentalizing deficits, social anxiety, and sensory
      reactivity relevant for the diagnosis of ASD. The psychometric properties of
      RAADS-14 Screen were shown to be satisfactory. CONCLUSIONS: The results of this
      study indicate that RAADS-14 Screen is a promising measure in screening for ASD
      in adult psychiatric outpatients.

PMID- 24321511
TI  - N-terminus regulation of VMAT2 mediates methamphetamine-stimulated efflux.
AB  - The 20 amino acid (AA) N-terminus of the vesicular monoamine transporter 2
      (VMAT2) was examined as a regulator of VMAT2 function. Removal of the first 16 or
      19 AAs of the N-terminus resulted in a molecule with reduced ability to sequester
      [(3)H]-5HT. A glutathione-S-transferase-construct of the N-terminus underwent
      phosphorylation in the presence of PKC at serines 15 and 18. These putative
      phosphorylation sites were examined for effects on function. Phospho-mimetic
      substitution of serines 15 and 18 with aspartate in the full-length VMAT2
      resulted in reduced [(3)H]-5HT sequestration and reduced methamphetamine (METH)
      stimulated efflux of preloaded [(3)H]-5HT. In contrast, mutation of serines 15
      and 18 to alanines maintained intact net substrate sequestration but eliminated
      METH-stimulated efflux of pre-accumulated [(3)H]-5HT. In summary, these data
      suggest a model in which the VMAT2 N-terminus regulates monoamine sequestration. 

PMID- 24321512
TI  - Congenital taurine deficiency in mice is associated with reduced sensitivity to
      nociceptive chemical stimulation.
AB  - The amino acid taurine is required for development and functioning of the central
      and peripheral nervous system where it exerts osmoregulatory, neuromodulatory and
      anti-apoptotic actions. It is subject to cellular import by the taurine
      transporter slc6a6. Absence of the transporter and consequently, absence of
      taurine leads to several neurologic deficits and sensory losses. In a slc6a6
      knock-out mouse model, consequences of congenital taurine deficiency were
      assessed in nociceptive sensory processes. The formalin assay, hot plate assay,
      and summated generator potentials in response to local nociceptive stimulation
      with gaseous CO2 were applied. Reduced responsiveness of slc6a6(-/-) mice to
      nociceptive stimulation was observed in particular to chemical nociceptive
      stimuli. Scl6a6 knock-out mice spent significantly less time licking the formalin
      injected paw and displayed smaller amplitudes of the nociceptive nasal mucosa
      potentials than wild-type mice (p=0.002 and 0.01 respectively). In contrast,
      withdrawal latencies on a hot plate did not significantly differ, suggesting that
      intracellular taurine deficits lead in particular to a hyposensitivity of
      nociceptive sensory neurons sensitive to noxious chemical stimulation. As
      hereditary absence of taurine affects biological processes of anatomical
      structure development, the altered nociceptive responses likely reflect
      consequences of compromised peripheral nervous system development. 

PMID- 24321514
TI  - Vaccination of channel catfish with extracellular products of Aeromonas
      hydrophila provides protection against infection by the pathogen.
AB  - Aeromonas hydrophila, a Gram-negative bacterium, is one of the economically
      important pathogens in modern aquaculture. Among various traits, extracellular
      products (ECP) secreted by the bacterium are considered to be essential factors
      for virulence. Whether vaccination with the ECP could produce immune protection
      in catfish against the pathogen was determined in this study. The results showed
      that fish vaccinated with ECP had 100% of relative percent survival (RPS) when
      challenged with the pathogen two weeks post vaccination. The anti-ECP serum from
      vaccinated fish could aggregate cells of homogeneous bacteria as well as other
      virulent strains (isolates) of A. hydrophila but not an A. veronii isolate and a
      low virulent field isolate. The agglutination titers increased from two weeks to
      four weeks post immunization and sustained a high level at week seven when the
      RPS remained at 100%. The anti-ECP serum could also provide naive fish with
      immediate protection against A. hydrophila as evidenced by passive immunization.
      Immunoblotting analysis showed that the anti-ECP serum contained antibodies that
      bound to specific targets, including protein and lipopolysaccharide-like
      molecules, in the ECP. Mass spectrometric analysis identified following putative
      proteins that may serve as important immunogens: chitinase, chitodextrinase,
      outer membrane protein85, putative metalloprotease, extracellular lipase,
      hemolysin and elastase. Findings revealed in this study suggest that, while ECP
      prepared in a conventional and convenient way could be a vaccine candidate,
      further characterization of antibody-mediated targets in the ECP would uncover
      quintessential antigens for the future development of highly efficacious
      vaccines. 

PMID- 24321515
TI  - Exploring nurses' confirmed expectations regarding health IT: a phenomenological
      study.
AB  - Health information technology (IT) benefits both patients and providers with
      respect to health care quality and perceived usefulness. Although existing
      research provides a preliminary understanding of nurses' perception of health IT,
      perceptions do not guide actions. This phenomenological study explored nurses'
      perceptions regarding electronic health records and bar code medication
      administration four months post implementation on a medical-surgical unit in an
      academic medical center. Ten staff nurses (8 females and 2 males) participated.
      We categorized the results into five themes from personal-level to organizational
      level confirmed expectations: (1) nurses' interaction with computer, (2) nursing
      performance regarding task accomplishment, (3) unit-specific teamwork, (4)
      interdisciplinary teamwork, and (5) quality of care. We discovered that effective
      health IT must be congruent with nursing expectations. IT professionals, nursing
      and organizational leaders may use findings to structure an environment
      supportive of effective health IT in nursing practice. 

PMID- 24321516
TI  - Metabolic pathways involved in Xin-Ke-Shu protecting against myocardial
      infarction in rats using ultra high-performance liquid chromatography coupled
      with quadrupole time-of-flight mass spectrometry.
AB  - Xin-Ke-Shu (XKS) is a patent drug used for coronary heart diseases in China. This
      study evaluated the protective effect of XKS against isoproterenol (ISO)-induced
      myocardial infarction (MI). For its underlying mechanism in rats with MI, a
      metabonomic approach was developed using ultra high-performance liquid
      chromatography coupled with quadrupole time-of-flight mass spectrometry
      (UPLC/QTOF-MS). Plasma metabolites were profiled in MI rats, pretreated orally
      with or without XKS. Two genres of metabolic biomarkers were used to elucidate
      the pharmacological action of XKS: pathological biomarkers and pharmaco
      biomarkers. Fifteen metabolites significantly varying between MI rats and normal
      rats were characterized as potential pathological biomarkers related to MI,
      including L-acetylcarnitine (1), L-isoleucyl-L-proline (2), tyramine (3),
      isobutyryl-L-carnitine (4), phytosphingosine (5), sphinganine (6), L
      palmitoylcarnitine (7), lysoPC(18:0) (8), uric acid (9), L-tryptophan (10),
      lysoPC(18:2) (11), lysoPC(16:0) (12), docosahexaenoic acid (13), arachidonic acid
      (14) and linoleic acid (15). Among them, eight (1-6, 9 and 10) were first
      reported as pathological biomarkers related to ISO-induced MI, which mainly
      involved into fatty acid beta-oxidation pathway, sphingolipid metabolism,
      proteolysis, tryptophan metabolism and purine metabolism. The metabolites
      significantly varying between MI rats with and without XKS pretreatment were
      considered as pharmaco biomarkers. A total of 17 pharmaco biomarkers were
      recognized, including 15 pathological biomarkers (1-15), hexanoylcarnitine (16)
      and tetradecanoylcarnitine (17). The results suggested that pretreatment of XKS
      protected metabolic perturbations in rats with MI, major via lipid pathways,
      amino acid metabolism and purine metabolism, which also provided a promising
      approach for evaluating the pharmacodynamics and mechanism of traditional Chinese
      medicines (TCM) formulas.

PMID- 24321517
TI  - Cumulative area pre-processing (CAP): a new treatment of UV data for the analysis
      of complex pharmaceutical mixtures.
AB  - A new approach to pre-processing of the UV spectral data in combination with
      chemometric techniques, aiming to obtain a significant amplification of the
      analytical information, is proposed. The single areas under the curve between two
      consecutive wavelengths were calculated along the full spectrum and therefore
      their cumulative sum was carried out. The method was called "cumulative area pre
      processing" (CAP) and applied to multicomponent pharmaceutical formulations to
      test its performance in improving the accuracy of the analysis. The proposed
      procedure has demonstrated high ability in the quantitative determination of the
      components present in very low amount compared to other. Three multicomponent
      drug formulations were analyzed by applying the partial least squares (PLS)
      algorithm to the UV data processed by CAP and the results compared with those
      carried out by using the same data without treatment and after derivative
      transformation. The best results in the determination of the components present
      in lower concentrations were obtained by applying the PLS models calculated on
      data processed by CAP and confirmed in the analysis of marketed drug products. 

PMID- 24321519
TI  - Association of vitamin D receptor gene polymorphisms with systemic lupus
      erythematosus: a meta-analysis.
AB  - OBJECTIVES: Vitamin D receptor gene polymorphisms has been shown to be associated
      with systemic lupus erythematosus (SLE). Several studies have been published
      which have investigated the association between VDR gene polymorphisms with SLE
      risk, but the results have been inconclusive. The study was designed to
      investigate whether the vitamin D receptor gene polymorphisms are associated with
      the risk of SLE. METHODS: A meta-analysis was conducted on associations between
      the vitamin D receptor gene polymorphisms and SLE using (1) allele contrast and
      (2) the recessive, (3) the dominant, and (4) the additive models. RESULTS: A
      total of 11 case-control studies of 1683 patients and 1883 unrelated healthy
      individuals were included. The results of meta-analysis indicated that the BsmI
      and FokI polymorphisms are associated with increased risk of SLE. The overall ORs
      are 2.14 [95%CI (1.20-3.82), p=0.01] ( BB + Bb vs. bb) and 1.75 [95%CI(1.03
      2.97), P=0.04]( FF + Ff vs. ff), respectively, while the ApaI and TaqI
      polymorphism were not associated. In subgroup analysis by ethnicity, the
      increased risk of SLE remained in the Asian subgroup for the BsmI and FokI
      polymorphism, whereas no significant association was found in other populations
      for other polymorphisms. CONCLUSIONS: The current study suggested that the BsmI
      and FokI polymorphism are associated with increased risk of SLE, especially in
      the Asian population, but further studies are needed to confirm our results.

PMID- 24321518
TI  - Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival.
AB  - BACKGROUND: The genetic changes in gastric adenocarcinoma are extremely complex
      and reliable tumor markers have not yet been identified. There are also
      remarkable geographical differences in the distribution of this disease. Our aim
      was to identify the most differentially regulated genes in 20 gastric
      adenocarcinomas from a Norwegian selection, compared to matched normal mucosa,
      and we have related our findings to prognosis, survival and chronic Helicobacter
      pylori infection. METHODS: Biopsies from gastric adenocarcinomas and adjacent
      normal gastric mucosa were obtained from 20 patients immediately following
      surgical resection of the tumor. Whole genome, cDNA microarray analysis was
      performed on the RNA isolated from the sample pairs to compare the gene
      expression profiles between the tumor against matched mucosa. The samples were
      microscopically examined to classify gastritis. The presence of H. pylori was
      examined using microscopy and immunohistochemistry. RESULTS: 130 genes showed
      differential regulation above a predefined cut-off level. Interleukin-8 (IL-8)
      and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the
      tumors. Very high CLDN1 expression in the tumor was identified as an independent
      and significant predictor gene of reduced post-operative survival. There were
      distinctly different expression profiles between the tumor group and the control
      mucosa group, and the histological subsets of mixed type, diffuse type and
      intestinal type cancer demonstrated further sub-clustering. Up-regulated genes
      were mapped to cell-adhesion, collagen-related processes and angiogenesis,
      whereas normal intestinal functions such as digestion and excretion were
      associated with down-regulated genes. We relate the current findings to our
      previous study on the gene response of gastric epithelial cells to H. pylori
      infection. CONCLUSIONS: CLDN1 was highly up-regulated in gastric cancer, and
      CLDN1 expression was independently associated with a poor post-operative
      prognosis, and may have important prognostic value. IL-8 and CLDN1 may represent
      central links between the gene response seen in acute H. pylori infection of
      gastric epithelial cells, and ultimately gastric cancer.

PMID- 24321520
TI  - Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from
      patients with Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in
      which abnormal Langerhans cells proliferate as either a localized lesion in a
      single bone or disseminated disease involving two or more organs or systems.
      Because the different LCH forms exhibit significantly elevated levels of
      inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading
      enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We
      looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues
      using quantitative real-time PCR and immunohistochemistry staining with anti
      MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV
      DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high
      risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all
      12 LCH-RO- patients (P = .029). With lower viral loads (0.002-0.033 copies/cell),
      an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in
      comparison with control tissues obtained from patients with reactive lymphoid
      hyperplasia (0/5; P = .0007), skin diseases not related to LCH in children
      younger than 2 years (0/11; P = .0007), or dermatopathic lymphadenopathy (5/20; P
      = .0002). The data, including frequent but lower viral loads and low large-T
      antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a
      reactive rather than a neoplastic process may be related to MCPyV infection. 

PMID- 24321521
TI  - Significance of Akt activation and AKT gene increases in soft tissue tumors.
AB  - To clarify the aberrations of AKT genes, their protein products and
      clinicopathologic significance in bone and soft tissue tumors, expression
      profiles of total Akt, its isoforms and activated Akt, and increases in copy
      number of AKT1/AKT2 genes were examined. Immunohistochemical analysis in 77 cases
      revealed overexpression of total Akt, Akt1, Akt2, and phosphorylated Akt in
      84.4%, 67.5%, 72.7%, and 71.4%, respectively. Positive results were also observed
      in benign lesions but at a lower frequency. Overexpression of Akt1 was more
      frequent than that of Akt2 in well-differentiated liposarcoma (6/7 versus 3/7
      cases) and schwannoma (4/4 versus 1/4 cases), whereas Akt2 overexpression and Akt
      activation were more frequent than Akt1 overexpression in malignant nerve sheath
      (3/4 and 4/4, respectively, versus 2/4 cases) and muscular tumors (8/9 and 8/9
      versus 4/9 cases). By fluorescence in situ hybridization analysis, increase of
      gene copy number was observed in 13.3% for AKT1 and in 25.0% for AKT2 due to
      polysomy of chromosome 14 or 19, respectively, but not gene amplification. One
      case of schwannoma exhibited polysomy of both chromosomes 14 and 19. Akt
      activation was correlated with total Akt cytoplasmic localization (P = .0031) and
      subsequent metastasis (P = .0454). Moreover, AKT2 gene increase correlated with
      tumor size (P = .0352) and metastasis (P = .0344). In conclusion, in a defined
      subset of bone and soft tissue tumors, including benign tumors, Akt was
      frequently overexpressed and activated, and AKT1/2 copy number was increased.
      Because abnormality of Akt/AKT correlated with clinicopathologic profiles, novel
      therapies targeting isoform-specific Akts may be useful for these particular
      types of tumors. 

PMID- 24321522
TI  - Histological analysis suggests an invasion-independent metastatic mechanism in
      alveolar soft part sarcoma.
AB  - Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor characterized by
      pseudoalveolar growths associated with abundant sinusoidal vessels. It has a high
      proclivity to blood-borne metastasis, but the exact mechanism of spread has not
      been widely discussed, and detailed histological analysis of vascular involvement
      is still lacking. In this study, we histologically analyzed 32 surgically
      resected ASPSs, with particular attention to the mode of vascular involvement.
      Among 188 instances of unequivocal vascular involvement, 184 (98%) were in the
      form of variously sized cohesive clusters that were completely enveloped by
      endothelial cells, confirmed by CD31 immunostaining. Discohesive intravascular
      tumor cells without endothelial wrapping were rare (2%). The clinical relevance
      of vascular involvement was supported by survival analysis where the average
      number of vascular involvements per slide was an independent risk factor for
      shorter progression-free survival. Our findings suggest that ASPSs do not
      actively break through the vascular walls to initiate the metastatic process.
      They instead suggest that ASPSs almost exclusively follow the recently postulated
      "invasion-independent mechanism" for entry into circulation, in which cancer
      cells are shed into vessels, while being completely enveloped by endothelial
      cells, and are subsequently entrapped at recipient organs. Because the latter
      mechanism is reportedly dependent on tumor angiogenesis and vascular remodeling,
      our data provide a morphological rationale for the use of anti-angiogenic therapy
      to treat ASPSs. 

PMID- 24321523
TI  - Tissue tablet method: an efficient tissue banking procedure applicable to both
      molecular analysis and frozen tissue microarray.
AB  - Frozen human tissues are necessary for research purposes, but tissue banking
      methods have not changed for more than a decade. Many institutions use cryovial
      tubes or plastic molds with an optimal cutting temperature compound. However,
      these methods are associated with several problems, such as samples sticking to
      one another and the need for a larger storing space. We established an efficient
      tissue freezing and storing procedure ("tissue tablet method") applicable to both
      molecular analysis and frozen tissue microarray. Tissue samples were chopped into
      tiny fragments and embedded into tablet-shaped frozen optimal cutting temperature
      compound using our original tissue-freezing plate. These tablets can be sectioned
      and stored in cryovial tubes. We compared the tissue quality of tablet-shaped
      samples with that of conventional optimal cutting temperature blocks and found no
      significant difference between them. Tissue microarray is a key method to utilize
      tissue-banking specimens. However, most tissue microarrays require the coring out
      of cylindrically shaped tissues from formalin-fixed, paraffin-embedded tissue
      blocks. Antigenic changes and mRNA degradation are frequently observed with
      formalin-fixed, paraffin-embedded samples. Therefore, we have applied tablet
      shaped samples to construct frozen tissue microarrays with our original mounting
      base. Constructed tissue microarray sections showed good morphology without
      obvious artifact and good immunohistochemistry and in situ hybridization results.
      These results suggest that the quality of arrayed samples was sufficiently
      appropriate for research purposes. In conclusion, the tissue tablet method and
      frozen tissue microarray procedure can save time, provides easy tissue handling
      and processing, and satisfies the demands of research methodologies and tissue
      banking. 

PMID- 24321524
TI  - Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of
      disease.
AB  - Cavitary pulmonary coccidioidomycosis is a difficult diagnosis to establish due
      to the poor sensitivity of serological tests and rarity of culture from sputum. A
      pathologic and clinical analysis was performed of 21 consecutive patients with
      surgically resected cavities that proved to be coccidioidomycosis. Ten patients
      (48%) had serological evidence of Coccidioides infection, and 1 patient cultured
      Coccidioides spp. from sputum. The definitive diagnosis of coccidioidomycosis was
      made in the remaining 10 patients (48%) upon microscopic examination of tissue.
      The pleura showed fibrous pleuritis in 7 patients (33%) and eosinophilic
      pleuritis in 4 cases (19%); granulomas without microorganisms were demonstrated
      in 4 cases (19%). The cavity wall showed chronic inflammation and occasional
      giant cells but no granulomas and no microorganisms. The cavity contents included
      a mycetoma in 6 cases (28%); the cavity lining showed neutrophils and caseous
      necrosis; Coccidioides hyphae were present in 13 (62%) and spherules in 16 (76%)
      cases but often were rare. Adjacent lung showed lymphoid hyperplasia with chronic
      bronchiolitis in all cases; satellite granulomas with diagnostic spherules were
      variably present. The histopathology of cavitary coccidioidomycosis is strikingly
      variable depending on what area is sampled by biopsy, and microorganisms may be
      rare. This may explain the high rate of failure of diagnosis by fine needle
      aspiration and bronchoalveolar lavage. Pathologists in nonendemic areas must be
      aware of these findings, as this disease is now diagnosed worldwide. 

PMID- 24321525
TI  - Different collagen types show distinct rates of increase from early to late
      stages of hepatitis C-related liver fibrosis.
AB  - During progression from normal liver to cirrhosis, total collagen increases
      nearly 10-fold with an abnormal increase in fibril-forming collagen and other
      extracellular matrix molecules. However, little is known regarding the changes
      each collagen type undergoes during fibrogenesis. We assessed the different
      collagen types by immunohistochemistry at various stages of hepatitis C-related
      liver fibrosis in core biopsies and compared changes in each with trichrome stain
      to better understand fibrogenesis. The possible utility in staging fibrosis was
      investigated. We found collagens III, IV, V, VI, vitronectin, and trichrome all
      showed statistically significant increases from early to late stages of fibrosis,
      but with temporal and quantitative differences. During the transition from early
      to late fibrosis, trichrome (stains primarily collagen I) and collagen IV showed
      the steepest increase and appear to be the most useful discriminators between
      early and late stages of fibrosis. Collagens V and VI have strong reactivity even
      in stage 1, which may be helpful in identifying early fibrosis when trichrome is
      weak or negative. Collagen III and vitronectin showed the most gradual increase.
      Interestingly, collagen V also showed increased staining in areas around
      inflammation/edema, which may overestimate established fibrosis as compared with
      trichrome. 

PMID- 24321526
TI  - Pleomorphic solid pseudopapillary neoplasm of the pancreas: degenerative change
      rather than high-grade malignant potential.
AB  - Solid pseudopapillary neoplasms (SPNs) are rare tumors of the pancreas
      characterized by poorly cohesive uniform cells with solid and pseudopapillary
      growth patterns. Nuclear pleomorphism is not a well-recognized feature of SPNs
      and may complicate differentiation from other pancreatic neoplasms. We compared
      histologic, immunohistochemical, and clinical features of 18 pleomorphic SPNs
      with 121 conventional SPNs. The prevalence of pleomorphic SPN was 12.9% (18/139).
      Pleomorphic SPNs arose in older patients (median, 45 years versus 32 years; P <
      .001), but no differences were found in sex, tumor location, recurrence, and
      metastasis when compared with conventional SPNs. Except for pleomorphic nuclei,
      other cytologic and histologic features of pleomorphic SPNs, such as growth
      pattern, tumor size, infiltrative pattern, tumor extension, mitosis, and Ki-67
      labeling index, were not different from those of conventional SPNs. Pleomorphic
      SPNs showed a significantly higher p53 protein expression (64.7% [11/17 cases])
      than that of conventional SPNs (1.8% [2/112 cases], P < .001). However,
      immunoreactivity for beta-catenin and E-cadherin was not different between
      pleomorphic and conventional SPNs. A TP53 gene mutation was observed in 2 of 3
      p53-immunoreactive pleomorphic SPNs. In summary, nuclear pleomorphism occurs in a
      subset of SPNs. They are more often p53 immunoreactive than SPNs without
      pleomorphism, and some harbor TP53 gene mutations. However, pleomorphic SPNs do
      not appear to be more aggressive than conventional SPNs. Low mitotic rate and Ki
      67 labeling index may suggest nuclear pleomorphisms as degenerative changes.
      Recognition of typical poorly cohesive tumor cells and immunohistochemical
      features could establish the correct diagnosis of SPNs. 

PMID- 24321527
TI  - Expression of tapasin in rainbow trout tissues and cell lines and up regulation
      in a monocyte/macrophage cell line (RTS11) by a viral mimic and viral infection.
AB  - Tapasin is a transmembrane glycoprotein that acts as a bridge between the
      transporter associated with antigen processing and the MHC class I receptor in
      mammals. Through the development of antibody against trout tapasin, this report
      demonstrates the detection of trout tapasin as a N-glycosylated 48 kDa protein.
      Tissue and cell line distribution revealed that tapasin protein is expressed
      mainly in immune system organs and in rainbow trout epithelial cell lines from
      gill (RTgill-W1), liver (RTL-W1), and intestine (RTgutGC). An additional 20 kDa
      band was observed in tissues and cell lines, and appeared to be most prominent in
      RTgutGC but was absent in peripheral blood leukocytes. Tapasin 48 kDa protein was
      most strongly expressed in RTS11 (monocyte/macrophage cell line) and its
      regulation following dsRNA stimulation was explored. Upon poly I:C treatment and
      Chum Salmon Reovirus (CSV) infection, tapasin protein expression was upregulated
      up to 3.5 fold and 3 fold respectively, in parallel with increased expression of
      the glycosylated MH class I heavy chain, whereas the expression of the 20 kDa
      form remained unchanged. Overall this work demonstrates the induction of tapasin
      protein by dsRNA stimulation, which implies its possible conserved regulation
      during viral infection in teleost cells.

PMID- 24321528
TI  - HIV integrase and the swan song of the CD4 T cells?
AB  - T cell apoptosis represents one pathophysiological mechanism associated with
      AIDS. Herein, we discuss the recent report published by A. Cooper et al. in
      Nature (June 2013) regarding HIV viral DNA integration-mediated apoptosis. 

PMID- 24321529
TI  - A sensitive in vitro assay for the detection of residual viable rabies virus in
      inactivated rabies vaccines.
AB  - Rabies is a viral disease transmitted through bites from rabid animals and can be
      prevented by vaccines. Clinically used rabies vaccines are prepared from
      inactivated rabies viruses grown in cell cultures or embryonated eggs. In Japan
      and across the world, tests that confirm complete inactivation, such as the in
      vivo suckling mouse assay, in which suckling mice are intracerebrally inoculated
      with vaccine products, are required for quality control. In this study, we
      developed a novel cell-based immunofluorescence assay that does not require mice
      for testing rabies vaccine inactivation for human use. The sensitivity of this
      cell-based in vitro assay was 5.7 times that of the in vivo suckling mouse assay,
      with a detection limit of one focus forming units per ml of test sample. This
      newly developed in vitro assay may replace the established in vivo suckling mouse
      assay for confirming viral vaccine inactivation. 

PMID- 24321530
TI  - Somatostatin enhances tooth-pulp-evoked cervical dorsal horn neuronal activity in
      the rat via inhibition of GABAergic interneurons.
AB  - A recent in vitro electrophysiological analysis combined with anatomical approach
      suggests that a potential disinhibitory mechanism involving somatostatin (SST),
      which is released by interneurons in the superficial dorsal horn, contributes to
      nociceptive transmission (Yasaka et al., 2010); however, whether this mechanism
      occurs in vivo remains to be determined. The aim of the present study was to
      investigate whether iontophoretic application of SST facilitates the excitability
      of nociceptive upper cervical spinal dorsal horn (C1) neurons through GABAergic
      disinhibiton, using extracellular electrophysiological recording with multibarrel
      electrodes and immunohistochemical techniques. Immunoreactivity of SST2A
      receptors was found in layer II of the C1 dorsal horn in the rat and most of
      these neurons co-expressed the GABA synthesizing enzyme glutamate decarboxylase
      67. Single-unit recordings were made from C1 neurons responding to tooth-pulp
      (TP) electrical stimulation in pentobarbital anesthestized rats. Iontophoretic
      application of SST significantly increased TP-evoked C1 neuronal discharges in
      layers I and II of the spinal dorsal horn and this effect occurred in a current
      dependent manner. The facilitation of this discharge by SST application was
      abolished with co-application of the SST2 receptor antagonist, Cyanamid 154806.
      Iontophoretic application of GABAA receptor antagonist, bicuculline, induced
      facilitation of TP-evoked C1 neuronal discharges. There was no significant
      difference in the relative number of spikes between SST and bicuculline
      applications. These results suggest that a local release of SST facilitates the
      excitability of trigeminal nocicepitve C1 neuronal activity via inhibition of
      GABAergic neurons. Therefore, SST2A receptors expressed in layer II GABAergic
      inhibitory interneurons play an important role in trigeminal nociceptive
      transmission and are a potential therapeutic target in the treatment of
      trigeminal pain, including hyperalgesia. 

PMID- 24321531
TI  - Defining futile life-prolonging treatments through Neo-Socratic Dialogue.
AB  - BACKGROUND: In Japan, people are negative towards life-prolonging treatments.
      Laws that regulate withholding or discontinuing life-prolonging treatments and
      advance directives do not exist. Physicians, however, view discontinuing life
      prolonging treatments negatively due to fears of police investigations. Although
      ministerial guidelines were announced regarding the decision process for end-of
      life care in 2007, a consensus could not be reached on the definition of end-of
      life and conditions for withholding treatment. We established a forum for
      extended discussions and consensus building on this topic. METHODS: We used the
      Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based
      on a case-study to address a question and formulate a consensus and answer in a
      group. The question chosen for the dialogue was: "What is a life-prolonging
      treatment?" A series of dialogues took place over a period of one and a half
      days. It was carried out by three groups in 2010 and 2011. Seven participants
      with diverse backgrounds were recruited per group. We analyzed the content of the
      discussion. RESULTS: Based on three case studies concerning different opinions
      about treatment options for an older dementia patient, a patient demanding
      chemotherapy, and a severely ill neonate, conditions for futile life-prolonging
      treatment were elucidated through NSD. Such treatments are those carried out for
      the sole purpose of prolonging life and are detrimental to the patient, and
      should be decided based foremost on the patient's lack of desire for treatment,
      the consensus of those involved, and through social acceptance. These arguments
      are essentially consistent with ones on medical futility in the United States. By
      expressing the objective of healthcare and the requirement of social acceptance,
      participants were also able to elucidate issues related to the awareness of those
      involved and the medical environment. Compared to the end-of-life guidelines in
      Japan, the objective of treatment, its effects, and benefits were more
      specifically discussed with the patient's intentions as the foremost
      consideration, rather than being limited to the terminal stage. CONCLUSIONS: This
      small study contributed to elucidating the conditions and current problems of
      futile life-prolonging treatment through NSD. They would suggest more substantial
      guidelines and improvements on the administration of the treatment.

PMID- 24321532
TI  - Obstructive sleep apnea and hypoxemia are associated with advanced liver
      histology in pediatric nonalcoholic fatty liver disease.
AB  - OBJECTIVE: To determine whether obstructive sleep apnea (OSA) and/or nocturnal
      hypoxemia are associated with the severity of liver injury in patients with
      pediatric nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: Obese children
      aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic,
      clinical, and laboratory data were collected, polysomnography was performed, and
      liver histology was scored. Subjects were divided into those with OSA/hypoxemia
      and those without OSA/hypoxemia for analysis. RESULTS: Of 25 subjects with NAFLD,
      OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 +/- 1.9 years; 68% male;
      88% Hispanic; mean body mass index z-score, 2.3 +/- 0.3). Subjects with and
      without OSA/hypoxemia had similar levels of serum aminotransferases, serum
      lipids, and inflammatory and insulin resistance markers. Although there were no
      differences between groups in the histological severity of steatosis,
      inflammation, ballooning degeneration, NAFLD activity score, or histological
      grade, subjects with OSA/hypoxemia had significantly more severe hepatic
      fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to
      hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level
      (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation <=90%
      was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic
      steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04),
      aspartate aminotransferase level (r = 0.56; P = .004), and alanine
      aminotransferase level (r = 0.44; P = .03). CONCLUSION: Moderate OSA/hypoxemia is
      common in pediatric patients with biopsy-proven NAFLD. OSA and the
      severity/duration of hypoxemia are associated with biochemical and histological
      measures of NAFLD severity.

PMID- 24321533
TI  - Bedside to bench: The risk of bleeding with parenteral omega-3 lipid emulsion
      therapy.
AB  - Our clinical experience led us to reassess the effect of sole omega-3 lipid
      therapy on hemostasis. We compared thromboelastography platelet mapping in
      neonatal piglets given sole omega-3 lipid. We identified abnormalities in
      reaction time (P = .025) and the arachidonic acid pathway (P = .025). The
      potential for bleeding complications from parenteral omega-3 lipid emulsion
      therapy in high-risk infants with liver disease has been dismissed but, on the
      basis of this data, should be reconsidered. 

PMID- 24321534
TI  - Clinical and molecular characteristics of mitochondrial DNA depletion syndrome
      associated with neonatal cholestasis and liver failure.
AB  - OBJECTIVE: To determine the frequency of mitochondrial DNA depletion syndrome
      (MDS) in infants with cholestasis and liver failure and to further clarify the
      clinical, biochemical, radiologic, histopathologic, and molecular features
      associated with MDS due to deoxyguanosine kinase (DGUOK) and MPV17 gene
      mutations. STUDY DESIGN: We studied 20 infants with suspected hepatocerebral MDS
      referred to our tertiary care center between 2007 and 2013. Genomic DNA was
      isolated from blood leukocytes, liver, and/or skeletal muscle samples by standard
      methods. Mitochondrial DNA copy number relative to nuclear DNA levels was
      determined in muscle and/or liver DNA using real-time quantitative polymerase
      chain reaction and compared with age-matched controls. Nuclear candidate genes,
      including polymerase gamma, MPV17, and DGUOK were sequenced using standard
      analyses. RESULTS: We identified pathogenic MPV17 and DGUOK mutations in 11
      infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis
      and 22% of the 50 cases of infantile liver failure referred to our center during
      the study period. All of the 11 patients manifested cholestasis that was followed
      by a rapidly progressive liver failure and death before 2 years of life.
      Mitochondrial DNA depletion was demonstrated in liver or muscle for 8 out of the
      11 cases where tissue was available. Seven patients had mutations in the MPV17
      gene (3 novel mutations), 4 patients had DGUOK mutations (of which 2 were novel
      mutations). CONCLUSION: Mutations in the MPV17 and DGUOK genes are present in a
      significant percentage of infants with liver failure and are associated with poor
      prognosis.

PMID- 24321535
TI  - Cumulative exposure to medical radiation for children requiring surgery for
      congenital heart disease.
AB  - OBJECTIVE: To describe cumulative radiation exposure in a large single-center
      cohort of children with congenital heart disease (CHD) and identify risk factors
      for greater exposure. STUDY DESIGN: A detailed medical radiation exposure history
      was collected retrospectively for patients aged <18 years who underwent surgery
      for CHD between January 1, 2001, and July 22, 2009. Cumulative per patient
      exposure was quantified as the effective dose in millisieverts (mSv) and
      annualized (mSv/year). RESULTS: A total of 4132 patients were subjected to
      134,715 radiation examinations at a median follow-up of 4.3 years (range, 0-8.6
      years). Exposure clustered around the time of surgery. The median exposure was 14
      radiologic tests (the majority of which were plain film radiographs) at an
      effective dose of 0.96 mSv (the majority of which was from cardiac
      catheterization), although this distribution had a very wide range. Almost three
      quarters (73.7%) were exposed to <3 mSv/year, and 5.3% were exposed to >20
      mSv/year. Neonates, children with genetic syndromes, and children requiring
      surgery for cardiomyopathy, pulmonary valve, single ventricle, or tricuspid valve
      diseases were more likely to have higher exposure levels, and those requiring
      surgery for aortic arch anomalies or atrioventricular septal defects were more
      likely to have lower levels. CONCLUSION: Children with CHD requiring surgery are
      exposed to numerous medical forms of ionizing radiation. Although the majority of
      patients receive <3 mSv/year, there are identifiable risk factors for higher
      exposure levels. This may have important health implications as these patients
      age.

PMID- 24321536
TI  - Puberty and plexiform neurofibroma tumor growth in patients with
      neurofibromatosis type I.
AB  - OBJECTIVE: To assess the relationship between pubertal progression and change in
      plexiform neurofibroma (PN) burden over time in pediatric and young adult
      patients with neurofibromatosis type 1 and PNs. STUDY DESIGN: Analyses accounted
      for sex, age, race, and chemotherapy. Forty-one patients with neurofibromatosis
      type 1 (15 female and 26 male patients) were studied at the National Institutes
      of Health. Tanner stage, testosterone, progesterone, estradiol, insulin-like
      growth factor -1, luteinizing hormone, and follicle-stimulating hormone were
      assessed. Tumor volume was measured using magnetic resonance imaging and lesion
      detection software developed locally. Patients were divided into 2 groups based
      on whether they were actively progressing through puberty (n = 16) or were
      peripubertal (n = 25) and were followed for an average of 20 months. Tumor growth
      rates in the puberty and peripubertal group were analyzed for a subset of
      patients. RESULTS: There was no statistically significant difference in tumor
      burden change over time (cm(2)/kg per month) between the pubertal and
      peripubertal groups (-0.16 +/- 0.34 vs 0.03 +/- 1.8, P = .31) and in the PN
      growth rates before and during puberty (P = .90). Change in tumor volume/patient
      weight/time did not correlate with testosterone change/time in males or estradiol
      change/time in females. CONCLUSION: These findings support that hormonal changes
      of puberty do not accelerate PN growth. Additional long-term follow-up of
      patients is necessary to further characterize the interaction between puberty and
      tumor growth.

PMID- 24321537
TI  - Functional outcomes in children with abusive head trauma receiving inpatient
      rehabilitation compared with children with nonabusive head trauma.
AB  - OBJECTIVE: To compare clinical features and functional outcomes of age- and sex
      matched children with abusive and nonabusive head trauma receiving inpatient
      rehabilitation. STUDY DESIGN: Children with abusive head trauma (n = 28) and age-
      and sex-matched children with nonabusive head trauma (n = 20) admitted to an
      inpatient pediatric rehabilitation unit from 1995-2012 were studied. Acute
      hospitalization and inpatient rehabilitation records were retrospectively
      reviewed for pertinent clinical data: initial Glasgow Coma Scale score, signs of
      increased intracranial pressure, neuroimaging findings, and presence of
      associated injuries. Functional status at admission to and discharge from
      inpatient rehabilitation was assessed using the Functional Independence Measure
      for Children. Outcome at discharge and outpatient follow-up were described based
      on attainment of independent ambulation and expressive language. RESULTS:
      Children with abusive and nonabusive head trauma had similar levels of injury
      severity, although associated injuries were greater in those with abusive head
      trauma. Functional impairment upon admission to inpatient rehabilitation was
      comparable, and functional gains during inpatient rehabilitation were similar
      between groups. More children with nonabusive than with abusive head trauma
      attained independent ambulation and expressive language after discharge from
      rehabilitation; the difference was no longer significant when only children aged
      >12 months at injury were examined. There was variability in delay to obtain
      these skills and in the quality of gained skills in both groups. CONCLUSIONS:
      Despite more associated injuries, children with abusive head trauma make
      significant functional gains during inpatient rehabilitation, comparable with an
      age- and sex-matched sample with nonabusive head trauma. Key functional skills
      may be gained by children in both groups following discharge from inpatient
      rehabilitation.

PMID- 24321538
TI  - Superior mesenteric artery blood flow velocities following medical treatment of a
      patent ductus arteriosus.
AB  - We examined superior mesenteric artery blood flow velocity in response to feeding
      in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during
      previous treatment for patent ductus arteriosus. Blood flow velocity increased
      earlier in the fed infants, but was similar in the 2 groups at 30 minutes after
      feeding. 

PMID- 24321539
TI  - Feasibility and safety of erythropoietin for neuroprotection after perinatal
      arterial ischemic stroke.
AB  - OBJECTIVE: To perform a feasibility and safety study with recombinant human
      erythropoietin (rhEPO) in neonates with perinatal arterial ischemic stroke. STUDY
      DESIGN: Neonates with a magnetic resonance imaging-confirmed perinatal arterial
      ischemic stroke (n = 21) were treated with 1000 IU/kg rhEPO immediately after
      diagnosis and at 24 and 48 hours after the first dose. Repeat magnetic resonance
      imaging was performed when the patients were 3 months of age. Coagulation and
      hematologic variables (red blood cells, white blood cells, platelet counts) were
      performed in the first week after initiation of treatment. We also compared 10
      patients who were treated with rhEPO with 10 historic infants with perinatal
      arterial ischemic stroke matched for the involved arterial branch to investigate
      whether rhEPO reduces the residual size of the infarction and subsequent brain
      growth between first and second scan. RESULTS: Seizures were a first symptom in
      20 of 21 neonates. Heart rate, blood pressure, and coagulation function were in
      the normal range, as were red blood cells, white blood cells, and platelet
      counts. In a subgroup of 10 rhEPO-treated neonates, no differences were detected
      in residual infarction volumes or neurodevelopmental outcome compared with their
      historical nontreated counterparts. CONCLUSIONS: rhEPO in neonates with perinatal
      arterial ischemic stroke had no adverse effects on red blood cells, white blood
      cells, platelets counts, or coagulation. rhEPO, 3000 IU/kg in total, given during
      a 3-day period, appears to be a safe therapy. The beneficial effects remains to
      be demonstrated in a larger, randomized, double-blind, placebo-controlled trial.

PMID- 24321540
TI  - Pulse oximetry is insufficient for timely diagnosis of hepatopulmonary syndrome
      in children with liver cirrhosis.
AB  - OBJECTIVE: To prospectively investigate the prevalence of hepatopulmonary
      syndrome (HPS), the importance of pulse oximetry in diagnosing HPS, and the
      longitudinal course after liver transplantation in children with cirrhosis
      referred for liver transplantation. STUDY DESIGN: Fifty-six patients aged 1-17
      years (mean age, 4.6 +/- 5.0 years) with liver cirrhosis were screened for HPS by
      hyperemic capillary blood gas (CBG) analysis and contrast-enhanced transthoracic
      echocardiography. Eleven patients were excluded owing to conditions that can
      produce cardiopulmonary dysfunction, including 5 with cystic fibrosis, 1 with
      pulmonary arterial hypertension, and 5 with an intracardial shunt. HPS was
      classified in accordance with the European Respiratory Society Task Force
      criteria on pulmonary-hepatic disorders. Patient groups were compared for
      biochemical and clinical characteristics. RESULTS: Eighteen children (40%) with
      cirrhosis were intrapulmonary vasodilatation (IPVD)-positive and had a pulse
      oximetry oxygen saturation level >98%. Two of these patients (11%) exhibited
      moderate HPS with an elevated alveolar arterial oxygen gradient >15 mm Hg and
      PaO2 <70 mm Hg; they died before undergoing liver transplantation. The
      sensitivity and specificity of CBG analysis for detecting elevated alveolar
      arterial oxygen gradient in children with IPVD was 94% and 53%, respectively. HPS
      was associated with late hepatoportoenterostomy (P < .04). Liver transplantation
      led to resolution of HPS in all patients. CONCLUSION: IPVD is frequent in
      children with liver cirrhosis (40%). Pulse oximetry is insufficient for timely
      HPS diagnosis. Pathological CBG analysis data indicate IPVD in the majority of
      cases, but are imprecise in children aged <2 years. Contrast-enhanced
      transthoracic echocardiography and CBG analysis are recommended for evaluation of
      HPS in children with cirrhosis, regardless of liver synthesis capacity and
      clinical chemistry data.

PMID- 24321541
TI  - A newborn with neurocutaneous melanocytosis and Dandy-Walker malformation.
AB  - BACKGROUND: Neurocutaneous melanocytosis is a rare congenital dysplasia of the
      neuroectodermal melanocyte precursor cells that leads to proliferation of melanin
      producing cells in the skin and leptomeninges. PATIENT: We describe a newborn
      with a giant congenital melanocytic nevus on his back, buttocks, and thighs. His
      brain magnetic resonance imaging study revealed bilateral T1 hyperintense lesions
      in the cerebellum and in the amygdala, hydrocephalus, and a Blake's pouch cyst,
      consistent with neurocutaneous melanocytosis and Dandy-Walker malformation.
      CONCLUSION: Neurocutaneous melanocytosis has a wide clinical spectrum that
      includes hydrocephalus, epilepsy, cranial nerve palsy, increased intracranial
      pressure, and sensorimotor deficits.

PMID- 24321542
TI  - Murine typhus as a cause of cognitive impairment: case report and a review of the
      literature.
AB  - BACKGROUND: Murine typhus is a systemic febrile illness caused by Rickettsia
      typhi, a gram-negative, obligate intracellular bacterium. It is found worldwide,
      including in the United States, where cases are concentrated in suburban areas of
      Texas and California. The disease manifests with fever, headache, and rash.
      Central nervous system involvement is rare in both adults and children. Aseptic
      meningitis and meningoencephalitis are the most common neurological
      presentations, occurring in 2% to 5% of cases. Neurological dysfunction,
      including memory impairment and behavioral alterations, can occur and usually are
      reversible. Long-term deficits are considered rare even in untreated cases and
      have not been described in the pediatric population. METHODS: Single case report.
      RESULTS: We describe a previously healthy 17-year-old girl infected with R. typhi
      who developed meningoencephalitis that resulted in chronic cognitive impairment
      despite treatment. CONCLUSION: Murine typhus should be considered in the
      differential diagnosis of aseptic meningitis and meningoencephalitis. Early
      diagnosis and treatment can prevent death and long-term morbidity.

PMID- 24321543
TI  - Management of pediatric migraine in a tertiary care versus community based
      emergency department: an observational pilot study.
AB  - BACKGROUND: Because of a lack of guidelines for the management of pediatric
      migraine in the emergency department setting, marked variations in treatment
      protocols exist between institutions. We aimed to characterize differences in
      management strategies for pediatric migraine treatment between a community-based
      and a tertiary care emergency department. METHODS: A retrospective cohort study
      was performed to include pediatric patients presenting with headache fulfilling
      the International Classification of Headache Disorders-2 migraine criteria in a
      tertiary care (site 1) and a community based (site 2) emergency department. The
      two sites were compared with respect to patient demographics and approach to
      treatment. RESULTS: A total of 158 patients at site 1 (mean age 13.6 years, 70%
      female, 68% African-American) and 63 patients at site 2 (mean age 16.7 years, 71%
      female, 100% Caucasian) were analyzed. Opiate use (7.6% vs. 33%), imaging (6.3%
      vs. 20.6%), use of nonsteroidal anti-inflammatory drugs/serotonin agonists at
      discharge (72.7% vs. 22.2%), and admission rates to hospital (22% vs. 0%) were
      significantly different. Logistic regression analysis indicated that the main
      predictors of hospital admission were use of opiates and intravenous combination
      abortive therapy. CONCLUSION: Low rates of intravenous combination therapy,
      antidopaminergic agent, and serotonin agonist use were noted across both hospital
      settings. Community-based physicians used opiates and obtained neuro-imaging more
      than those in the academic setting. Standardization of care in the emergency
      setting coupled with reliable acute care plans that are based on evidenced-based
      guidelines can allow for better control of episodic migraine and reduce emergency
      department visits.

PMID- 24321544
TI  - Recurrent Miller Fisher syndrome in children.
AB  - BACKGROUND: Miller Fisher syndrome is usually a monophasic disorder. Recurrent
      Miller Fisher syndrome is extremely rare, and all patients with recurrences have
      been adults. Although the optimal treatment for Miller Fisher syndrome has yet to
      be established, the typical therapy includes intravenous immunoglobulin or plasma
      exchange. The efficacy of steroids is still debated. PATIENTS: We describe two
      children with recurrent Miller Fisher syndrome. Episodes occurred at the age of
      11.5 and 13 years in patient 1 and at the age of 8 and 13 years in patient 2.
      RESULTS: Clinical patterns of the first and recurrent episodes of Miller Fisher
      syndrome were overlapping. In both patients, steroids were effective in
      controlling clinical deterioration of Miller Fisher syndrome recurrences.
      CONCLUSIONS: Recurrent Miller Fisher syndrome is a rare disorder that may occur
      in children. Our observations and a review of the literature suggest that there
      may be a small group of patients in whom steroids may be a therapeutic option
      when intravenous immunoglobulin fails to control clinical symptoms.

PMID- 24321545
TI  - SBML qualitative models: a model representation format and infrastructure to
      foster interactions between qualitative modelling formalisms and tools.
AB  - BACKGROUND: Qualitative frameworks, especially those based on the logical
      discrete formalism, are increasingly used to model regulatory and signalling
      networks. A major advantage of these frameworks is that they do not require
      precise quantitative data, and that they are well-suited for studies of large
      networks. While numerous groups have developed specific computational tools that
      provide original methods to analyse qualitative models, a standard format to
      exchange qualitative models has been missing. RESULTS: We present the Systems
      Biology Markup Language (SBML) Qualitative Models Package ("qual"), an extension
      of the SBML Level 3 standard designed for computer representation of qualitative
      models of biological networks. We demonstrate the interoperability of models via
      SBML qual through the analysis of a specific signalling network by three
      independent software tools. Furthermore, the collective effort to define the SBML
      qual format paved the way for the development of LogicalModel, an open-source
      model library, which will facilitate the adoption of the format as well as the
      collaborative development of algorithms to analyse qualitative models.
      CONCLUSIONS: SBML qual allows the exchange of qualitative models among a number
      of complementary software tools. SBML qual has the potential to promote
      collaborative work on the development of novel computational approaches, as well
      as on the specification and the analysis of comprehensive qualitative models of
      regulatory and signalling networks.

PMID- 24321546
TI  - Synthesis and antimicrobial activity of cysteine-free coprisin nonapeptides.
AB  - Coprisin is a 43-mer defensin-like peptide from the dung beetle, Copris
      tripartitus. CopA3 (LLCIALRKK-NH2), a 9-mer peptide containing a single free
      cysteine residue at position 3 of its sequence, was derived from the alpha
      helical region of coprisin and exhibits potent antibacterial and anti
      inflammatory activities. The single cysteine implies a tendency for dimerization;
      however, it remains unknown whether this cysteine residue is indispensible for
      CopA3's antimicrobial activity. To address this issue, in the present study we
      synthesized eight cysteine-substituted monomeric CopA3 analogs and two dimeric
      analogs, CopA3 (Dimer) and CopIK (Dimer), and evaluated their antimicrobial
      effects against bacteria and fungi, as well as their hemolytic activity toward
      human erythrocytes. Under physiological conditions, CopA3 (Mono) exhibits a 6/4
      (monomer/dimer) molar ratio in HPLC area percent, indicating that its effects on
      bacterial strains likely reflect a CopA3 (Mono)/CopA3 (Dimer) mixture. We also
      report the identification of CopW, a new cysteine-free nonapeptide derived from
      CopA3 that has potent antimicrobial activity with virtually no hemolytic
      activity. Apparently, the cysteine residue in CopA3 is not essential for its
      antimicrobial function. Notably, CopW also exhibited significant synergistic
      activity with ampicillin and showed more potent antifungal activity than either
      wild-type coprisin or melittin.

PMID- 24321547
TI  - PPAR-gamma agonist stabilizes KLF4 protein via activating Akt signaling and
      reducing KLF4 ubiquitination.
AB  - Peroxisome proliferator activated receptor gamma (PPAR-gamma) plays important
      roles in cell cycle regulation, differentiation and apoptosis. Kruppel-like
      factor 4 (KLF4) modulates vascular smooth muscle cell (VSMC) phenotype. Both KLF4
      and PPAR-gamma are involved in VSMC proliferation and differentiation. However,
      the actual relationship between KLF4 and PPAR-gamma in VSMCs is not clear. In
      this study, we found that PPAR-gamma agonist pioglitazone increases KLF4 protein
      levels but does not influence KLF4 gene transcription. PPAR-gamma overexpression
      increases, while PPAR-gamma knockdown reduces KLF4 expression, suggesting that
      the increase in KLF4 protein levels induced by pioglitazone is PPAR-gamma
      dependent. Further study showed that pioglitazone enhances KLF4 protein stability
      through reducing KLF4 ubiquitination. Furthermore, we demonstrated that
      stabilization of KLF4 by pioglitazone was related to the activation of Akt
      signaling pathway. Taken together, we revealed that PPAR-gamma agonist
      pioglitazone stabilizes KLF4 protein via activating Akt signaling and reducing
      KLF4 ubiquitination, providing further insights into PPAR-gamma and KLF4 in
      regulating each other's expression in VSMCs. 

PMID- 24321548
TI  - The multiple expression of Ca2+-activated Cl- channels via homo- and hetero-dimer
      formation of TMEM16A splicing variants in murine portal vein.
AB  - Ca(2+)-activated Cl(-) channel (CaCC) often plays substantial roles in the
      regulation of membrane excitability in smooth muscle cells (SMCs). TMEM16A, a
      member of the TMEM16 family, has been suggested as the molecular entity
      responsible for CaCC in several types of SMCs. In this study, the expression of
      TMEM16A splicing variants and their contribution to CaCC activity were examined
      in murine portal vein SMCs (mPVSMCs). Four transcripts of TMEM16A splicing
      variants, which include four alternatively spliced segments ("a" and "b" in N
      terminus and "c" and "d" in the first intracellular loop), were identified; the
      expression ratio of four transcripts of "abc", "acd", "abcd" and "ac" was 64.5,
      25.8, 4.8 and 4.8%, respectively. The immunostaining of isolated mPVSMCs with
      anti-TMEM16A antibody indicates the abundant expression of TMEM16A on the cell
      membrane. CaCC currents recorded in mPVSMCs were markedly reduced by T16A(inh)
      A01, a specific TMEM16A inhibitor. When the two major TMEM16A splicing variants,
      abc and acd isoforms, were expressed separately in HEK293 cells, the CaCC
      currents, which possess similar electrophysiological characteristics to those in
      mPVSMCs were observed. The single-molecule photobleaching analyses using total
      internal reflection fluorescence (TIRF) microscope indicated that the
      distribution of stepwise photobleaching events was fit well with a binomial
      distribution for homodimer. Additionally, the heterodimer formation was suggested
      by fluorescence resonance energy transfer (FRET) analyses in HEK293 cells co
      expressing CFP- or YFP-tagged variants. In conclusion, alternatively spliced
      variants of TMEM16A abc and acd in mPVSMCs are two major molecular entities of
      CaCC and may form hetero-/homo-dimers to be functional as CaCC in the regulation
      of membrane excitability and contractility in mPVSMCs.

PMID- 24321549
TI  - Inhibition of aldolase A blocks biogenesis of ATP and attenuates Japanese
      encephalitis virus production.
AB  - Viral replication depends on host proteins to supply energy and replication
      accessories for the sufficient production of viral progeny. In this study, we
      identified fructose-bisphosphate aldolase A as a binding partner of Japanese
      encephalitis virus (JEV) untranslated regions (UTRs) on the antigenome via RNA
      affinity capture and mass spectrometry. Direct interaction of aldolase A with JEV
      RNAs was confirmed by gel mobility shift assay and colocalization with active
      replication of double-stranded RNA in JEV-infected cells. Infection of JEV caused
      an increase in aldolase A expression of up to 33%. Knocking down aldolase A
      reduced viral translation, genome replication, and viral production
      significantly. Furthermore, JEV infection consumed 50% of cellular ATP, and the
      ATP level decreased by 70% in the aldolase A-knockdown cells. Overexpression of
      aldolase A in aldolase A-knockdown cells increased ATP levels significantly.
      Taken together, these results indicate that JEV replication requires aldolase A
      and consumes ATP. This is the first report of direct involvement of a host
      metabolic enzyme, aldolase A protein, in JEV replication. 

PMID- 24321550
TI  - Identification of novel dendritic cell subset markers in human blood.
AB  - Human dendritic cells (DC) are key regulators of innate and adaptive immunity
      that can be divided in at least three major subpopulations: plasmacytoid DC
      (pDC), myeloid type 1 DC (mDC1) and myeloid type 2 DC (mDC2) exhibiting different
      functions. However, research, diagnostic and cell therapeutic studies on human DC
      subsets are limited because only few DC subset markers have been identified so
      far. Especially mDC2 representing the rarest blood DC subset are difficult to be
      separated from mDC1 and pDC due to a paucity of mDC2 markers. We have combined
      multiparameter flow cytometry analysis of human blood DC subsets with systematic
      expression analysis of 332 surface antigens in magnetic bead-enriched blood DC
      samples. The initial analysis revealed eight novel putative DC subset markers
      CD26, CD85a, CD109, CD172a, CD200, CD200R, CD275 and CD301 that were subsequently
      tested in bulk peripheral blood mononuclear cell (PBMC) samples from healthy
      blood donors. Secondary analysis of PBMC samples confirmed three novel DC subset
      markers CD26 (dipeptidyl peptidase IV), CD85a (Leukocyte immunoglobulin-like
      receptor B3) and CD275 (inducible costimulator ligand). CD85a is specifically
      expressed in mDC1 and CD26 and CD275 represent novel mDC2 markers. These markers
      will facilitate human DC subset discrimination and additionally provide insight
      into potentially novel DC subset-specific functions. 

PMID- 24321552
TI  - Reciprocal regulation of LXRalpha activity by ASXL1 and ASXL2 in lipogenesis.
AB  - Liver X receptor alpha (LXRalpha), a member of the nuclear receptor superfamily,
      plays a pivotal role in hepatic cholesterol and lipid metabolism, regulating the
      expression of genes associated with hepatic lipogenesis. The additional sex comb
      like (ASXL) family was postulated to regulate chromatin function. Here, we
      investigate the roles of ASXL1 and ASXL2 in regulating LXRalpha activity. We
      found that ASXL1 suppressed ligand-induced LXRalpha transcriptional activity,
      whereas ASXL2 increased LXRalpha activity through direct interaction in the
      presence of the ligand. Chromatin immunoprecipitation (ChIP) assays showed ligand
      dependent recruitment of ASXLs to ABCA1 promoters, like LXRalpha. Knockdown
      studies indicated that ASXL1 inhibits, while ASXL2 increases, lipid accumulation
      in H4IIE cells, similar to their roles in transcriptional regulation. We also
      found that ASXL1 expression increases under fasting conditions, and decreases in
      insulin-treated H4IIE cells and the livers of high-fat diet-fed mice. Overall,
      these results support the reciprocal role of the ASXL family in lipid homeostasis
      through the opposite regulation of LXRalpha. 

PMID- 24321553
TI  - An assessment of existing models for individualized breast cancer risk estimation
      in a screening program in Spain.
AB  - BACKGROUND: The aim of this study was to evaluate the calibration and
      discriminatory power of three predictive models of breast cancer risk. METHODS:
      We included 13,760 women who were first-time participants in the Sabadell
      Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of
      risk were obtained at three and five years for invasive cancer using the Gail,
      Chen and Barlow models. Incidence and mortality data were obtained from the
      Catalan registries. The calibration and discrimination of the models were
      assessed using the Hosmer-Lemeshow C statistic, the area under the receiver
      operating characteristic curve (AUC) and the Harrell's C statistic. RESULTS: The
      Gail and Chen models showed good calibration while the Barlow model overestimated
      the number of cases: the ratio between estimated and observed values at 5 years
      ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the
      Barlow model. The 5-year projection for the Chen and Barlow models had the
      highest discrimination, with an AUC around 0.58. The Harrell's C statistic showed
      very similar values in the 5-year projection for each of the models. Although
      they passed the calibration test, the Gail and Chen models overestimated the
      number of cases in some breast density categories. CONCLUSIONS: These models
      cannot be used as a measure of individual risk in early detection programs to
      customize screening strategies. The inclusion of longitudinal measures of breast
      density or other risk factors in joint models of survival and longitudinal data
      may be a step towards personalized early detection of BC.

PMID- 24321551
TI  - Accumulation of nano-sized particles in a murine model of angiogenesis.
AB  - PURPOSE: To evaluate the ability of nm-scaled iron oxide particles conjugated
      with Azure A, a classic histological dye, to accumulate in areas of angiogenesis
      in a recently developed murine angiogenesis model. MATERIALS AND METHODS: We
      characterised the Azure A particles with regard to their hydrodynamic size, zeta
      potential, and blood circulation half-life. The particles were then investigated
      by Magnetic Resonance Imaging (MRI) in a recently developed murine angiogenesis
      model along with reference particles (Ferumoxtran-10) and saline injections.
      RESULTS: The Azure A particles had a mean hydrodynamic diameter of 51.8 +/- 43.2
      nm, a zeta potential of -17.2 +/- 2.8 mV, and a blood circulation half-life of
      127.8 +/- 74.7 min. Comparison of MR images taken pre- and 24-h post-injection
      revealed a significant increase in R2(*) relaxation rates for both Azure A and
      Ferumoxtran-10 particles. No significant difference was found for the saline
      injections. The relative increase was calculated for the three groups, and showed
      a significant difference between the saline group and the Azure A group, and
      between the saline group and the Ferumoxtran-10 group. However, no significant
      difference was found between the two particle groups. CONCLUSION: Ultrahigh-field
      MRI revealed localisation of both types of iron oxide particles to areas of
      neovasculature. However, the Azure A particles did not show any enhanced
      accumulation relative to Ferumoxtran-10, suggesting the accumulation in both
      cases to be passive.

PMID- 24321554
TI  - Neural systems for choice and valuation with counterfactual learning signals.
AB  - The purpose of this experiment was to test a computational model of reinforcement
      learning with and without fictive prediction error (FPE) signals to investigate
      how counterfactual consequences contribute to acquired representations of action
      specific expected value, and to determine the functional neuroanatomy and
      neuromodulator systems that are involved. 80 male participants underwent dietary
      depletion of either tryptophan or tyrosine/phenylalanine to manipulate serotonin
      (5HT) and dopamine (DA), respectively. They completed 80 rounds (240 trials) of a
      strategic sequential investment task that required accepting interim losses in
      order to access a lucrative state and maximize long-term gains, while being
      scanned. We extended the standard Q-learning model by incorporating both
      counterfactual gains and losses into separate error signals. The FPE model
      explained the participants' data significantly better than a model that did not
      include counterfactual learning signals. Expected value from the FPE model was
      significantly correlated with BOLD signal change in the ventromedial prefrontal
      cortex (vmPFC) and posterior orbitofrontal cortex (OFC), whereas expected value
      from the standard model did not predict changes in neural activity. The depletion
      procedure revealed significantly different neural responses to expected value in
      the vmPFC, caudate, and dopaminergic midbrain in the vicinity of the substantia
      nigra (SN). Differences in neural activity were not evident in the standard Q
      learning computational model. These findings demonstrate that FPE signals are an
      important component of valuation for decision making, and that the neural
      representation of expected value incorporates cortical and subcortical structures
      via interactions among serotonergic and dopaminergic modulator systems. 

PMID- 24321555
TI  - Exploring mechanisms of spontaneous functional connectivity in MEG: how delayed
      network interactions lead to structured amplitude envelopes of band-pass filtered
      oscillations.
AB  - Spontaneous (or resting-state) brain activity has attracted a growing body of
      neuroimaging research over the last decades. Whole-brain network models have
      proved helpful to investigate the source of slow (<0.1 Hz) correlated hemodynamic
      fluctuations revealed in fMRI during rest. However, the mechanisms mediating
      resting-state long-distance correlations and the relationship with the faster
      neural activity remain unclear. Novel insights coming from MEG studies have shown
      that the amplitude envelopes of alpha- and beta-frequency oscillations (~8-30 Hz)
      display similar correlation patterns as the fMRI signals. In this work, we
      combine experimental and theoretical work to investigate the mechanisms of
      spontaneous MEG functional connectivity. Using a simple model of coupled
      oscillators adapted to incorporate realistic whole-brain connectivity and
      conduction delays, we explore how slow and structured amplitude envelopes of band
      pass filtered signals - fairly reproducing MEG data collected from 10 healthy
      subjects at rest - are generated spontaneously in the space-time structure of the
      brain network. Our simulation results show that the large-scale neuroanatomical
      connectivity provides an optimal network structure to support a regime with
      metastable synchronization. In this regime, different subsystems may temporarily
      synchronize at reduced collective frequencies (falling in the 8-30 Hz range due
      to the delays) while the global system never fully synchronizes. This mechanism
      modulates the frequency of the oscillators on a slow time-scale (<0.1 Hz) leading
      to structured amplitude fluctuations of band-pass filtered signals. Taken
      overall, our results reveal that the structured amplitude envelope fluctuations
      observed in resting-state MEG data may originate from spontaneous synchronization
      mechanisms naturally occurring in the space-time structure of the brain.

PMID- 24321556
TI  - Temporal frequency tuning of cortical face-sensitive areas for individual face
      perception.
AB  - In a highly dynamic visual environment the human brain needs to rapidly
      differentiate complex visual patterns, such as faces. Here, we defined the
      temporal frequency tuning of cortical face-sensitive areas for face
      discrimination. Six observers were tested with functional magnetic resonance
      imaging (fMRI) when the same or different faces were presented in blocks at 11
      frequency rates (ranging from 1 to 12 Hz). We observed a larger fMRI response for
      different than same faces - the repetition suppression/adaptation effect - across
      all stimulation frequency rates. Most importantly, the magnitude of the
      repetition suppression effect showed a typical Gaussian-shaped tuning function,
      peaking on average at 6 Hz for all face-sensitive areas of the ventral occipito
      temporal cortex, including the fusiform and occipital "face areas" (FFA and OFA),
      as well as the superior temporal sulcus. This effect was due both to a maximal
      response to different faces in a range of 3 to 6 Hz and to a sharp drop of the
      blood oxygen level dependent (BOLD) signal from 6 Hz onward when the same face
      was repeated during a block. These observations complement recent scalp EEG
      observations (Alonso-Prieto et al., 2013), indicating that the cortical face
      network can discriminate each individual face when these successive faces are
      presented every 160-170 ms. They also suggest that a relatively fast 6 Hz rate
      may be needed to isolate the contribution of high-level face perception processes
      during behavioral discrimination tasks. Finally, these findings carry important
      practical implications, allowing investigators to optimize the stimulation
      frequency rates for observing the largest repetition suppression effects to faces
      and other visual forms in the occipito-temporal cortex.

PMID- 24321557
TI  - Additive genetic effect of APOE and BDNF on hippocampus activity.
AB  - Human memory is a highly heritable polygenic trait with complex inheritance
      patterns. To study the genetics of memory and memory-related diseases,
      hippocampal functioning has served as an intermediate phenotype. The importance
      of investigating gene-gene effects on complex phenotypes has been emphasized, but
      most imaging studies still focus on single polymorphisms. APOE epsilon4 and BDNF
      Met, two of the most studied gene variants for variability in memory performance
      and neuropsychiatric disorders, have both separately been related to poorer
      episodic memory and altered hippocampal functioning. Here, we investigated the
      combined effect of APOE and BDNF on hippocampal activation (N=151). No non
      additive interaction effects were seen. Instead, the results revealed decreased
      activation in bilateral hippocampus and parahippocampus as a function of the
      number of APOE epsilon4 and BDNF Met alleles present (neither, one, or both). The
      combined effect was stronger than either of the individual effects, and both gene
      variables explained significant proportions of variance in BOLD signal change.
      Thus, there was an additive gene-gene effect of APOE and BDNF on medial temporal
      lobe (MTL) activation, showing that a larger proportion of variance in brain
      activation attributed to genetics can be explained by considering more than one
      gene variant. This effect might be relevant for the understanding of normal
      variability in memory function as well as memory-related disorders associated
      with APOE and BDNF. 

PMID- 24321558
TI  - The similarity structure of distributed neural responses reveals the multiple
      representations of letters.
AB  - Most cognitive theories of reading and spelling posit modality-specific
      representations of letter shapes, spoken letter names, and motor plans as well as
      abstract, amodal letter representations that serve to unify the various modality
      specific formats. However, fundamental questions remain regarding the very
      existence of abstract letter representations, the neuro-topography of the
      different types of letter representations, and the degree of cortical selectivity
      for orthographic information. We directly test quantitative models of the
      similarity/dissimilarity structure of distributed neural representations of
      letters using Multivariate Pattern Analysis-Representational Similarity Analysis
      (MVPA-RSA) searchlight methods to analyze the BOLD response recorded from single
      letter viewing. These analyses reveal a left hemisphere ventral temporal region
      selectively tuned to abstract letter representations as well as substrates tuned
      to modality-specific (visual, phonological and motoric) representations of
      letters. The approaches applied in this research address various shortcomings of
      previous studies that have investigated these questions and, therefore, the
      findings we report serve to advance our understanding of the nature and format of
      the representations that occur within the various sub-regions of the large-scale
      networks used in reading and spelling. 

PMID- 24321559
TI  - MR vascular fingerprinting: A new approach to compute cerebral blood volume, mean
      vessel radius, and oxygenation maps in the human brain.
AB  - In the present study, we describe a fingerprinting approach to analyze the time
      evolution of the MR signal and retrieve quantitative information about the
      microvascular network. We used a Gradient Echo Sampling of the Free Induction
      Decay and Spin Echo (GESFIDE) sequence and defined a fingerprint as the ratio of
      signals acquired pre- and post-injection of an iron-based contrast agent. We then
      simulated the same experiment with an advanced numerical tool that takes a
      virtual voxel containing blood vessels as input, then computes microscopic
      magnetic fields and water diffusion effects, and eventually derives the expected
      MR signal evolution. The parameter inputs of the simulations (cerebral blood
      volume [CBV], mean vessel radius [R], and blood oxygen saturation [SO2]) were
      varied to obtain a dictionary of all possible signal evolutions. The best fit
      between the observed fingerprint and the dictionary was then determined by using
      least square minimization. This approach was evaluated in 5 normal subjects and
      the results were compared to those obtained by using more conventional MR
      methods, steady-state contrast imaging for CBV and R and a global measure of
      oxygenation obtained from the superior sagittal sinus for SO2. The fingerprinting
      method enabled the creation of high-resolution parametric maps of the
      microvascular network showing expected contrast and fine details. Numerical
      values in gray matter (CBV=3.1+/-0.7%, R=12.6+/-2.4MUm, SO2=59.5+/-4.7%) are
      consistent with literature reports and correlated with conventional MR
      approaches. SO2 values in white matter (53.0+/-4.0%) were slightly lower than
      expected. Numerous improvements can easily be made and the method should be
      useful to study brain pathologies. 

PMID- 24321560
TI  - Possible linkage between microscopic polyangiitis and thrombosis via neutrophil
      extracellular traps.

PMID- 24321561
TI  - Ommaya reservoir infections: a 16-year retrospective analysis.
AB  - OBJECTIVES: Ommaya reservoirs (OmR) are used in the treatment of cancer yet risk
      factors and outcome of infection are not well characterized. We therefore
      examined our experience with this device. METHODS: Using administrative
      databases, we identified all patients with OmR in situ between 1993 and 2008 at
      Memorial Sloan-Kettering Cancer Center. Charts were reviewed for laboratory,
      demographic, and clinical information. RESULTS: During the study period, 616
      patients with OmRs received care at MSKCC comprising 462,467 Ommaya-days. 34
      patients with OmR infection were identified (5.5% of patients, 0.74 infections
      per 10,000 Ommaya-days). 32% of infections occurred within 30 days of OmR
      placement. Most (74%) OmR infections occurring after 30 days post-placement were
      associated with OmR access in the preceding 30 days. Recovered organisms included
      coagulase-negative staphylococci (56%) and Propionibacterium acnes (24%). 70% of
      patients had fever and/or headache and 69% had cerebrospinal fluid pleocytosis.
      50% of patients had the reservoir removed during treatment of the infection.
      CONCLUSIONS: OmR infection occurs in one of every 20 persons with the device. A
      third of the infections appear related to OmR placement while the remainder may
      occur at any time and usually are associated with recent reservoir access.
      Treatment often includes device removal.

PMID- 24321562
TI  - Psychometric properties of the DCD-Q-07 in children ages to 4-6.
AB  - It is important to identify Developmental Coordination Disorder (DCD) early in a
      child's life to allow for proper and timely intervention and support, and to
      reduce the negative secondary consequences associated with this condition. In
      this study we assessed the psychometric properties (construct validity,
      concurrent validity, reliability and test accuracy) of the Developmental
      Coordination Disorder Questionnaire (DCD-Q-07) in preschool children. A community
      based sample of children ages 4-6 (n=181) were screened for motor difficulties
      using the Movement Assessment Battery for Children (M-ABC-2). Use of the M-ABC-2
      resulted in the identification of 29 children below the 15th percentile, which we
      classified as probable DCD. Parents of these children concurrently completed the
      DCD-Q-07 to report their child's motor performance. The DCD-Q-07 demonstrated
      high internal consistency for both the full scale (alpha=0.881) and each
      subscale: control during movement (alpha=0.813), fine motor and handwriting
      (alpha=0.869) and general coordination (alpha=0.728). Moderate correlations
      (r=0.47-0.63) were also seen between the subscales on the DCD-Q-07, the strongest
      correlation being between control during movement and general coordination
      (r=0.63). Based on published age and sex cut points, the DCD-Q-07 showed poor
      sensitivity (20.7%) but high specificity (92.1%) against the M-ABC-2. Overall
      agreement with the M-ABC-2 was low using ROC analysis (area under the
      curve=0.654). Although it is important to screen for DCD in young children, the
      DCD-Q-07 may not be the best choice as a screening tool for DCD in preschool
      children ages 4-6 due to its low test accuracy. 

PMID- 24321563
TI  - A comparative study of renal function in male and female spiny mice - sex
      specific responses to a high salt challenge.
AB  - BACKGROUND: There is a significant body of evidence to suggest that hormone
      levels, receptor density and structural differences between males and females can
      significantly alter renal hemodynamics. We compared the renal hemodynamic and
      excretory profile of female and male spiny mice under baseline conditions and in
      response to a high-NaCl diet. METHODS: Adult male and female spiny mice were fed
      either a normal or high salt diet for 7 days. Renal excretory profile was
      obtained from 24 h urine samples, and renal hemodynamic measurements using
      anaesthetised renal clearance techniques. Kidneys were excised, weighed and
      frozen for qPCR analysis. RESULTS: Under basal conditions, conscious and
      anaesthetised renal functions were similar between male and female spiny mice
      when adjusted for body weights. Male and female spiny mice on the high-NaCl diet
      had significantly greater GFR than sex matched controls (PDIET < 0.001). However
      the magnitude of the effect of salt was sex dependent (PSEX < 0.001; PINT <
      0.01). Male spiny mice showed a greater increase in GFR (84% higher than normal
      salt males) compared to females (33% higher than normal salt females), despite
      similar increases in renal plasma flow. In response to 7 days of high salt diet,
      female spiny mice showed a greater increase in 24-hour water consumption (45%
      more) and urinary output (50% more) compared to males (PINT < 0.01). These sex
      differences could not be explained by differences in renal expression of the V2R
      or AQP3 channel. CONCLUSION: These studies have identified major differences
      between male and female spiny mice in their renal response to a high-NaCl load
      suggesting that renal hemodynamics may be differentially regulated for the sexes.

PMID- 24321564
TI  - HIV integration and T cell death: additional commentary.
AB  - Estaquier et al. provide commentary on our paper that elucidated the mechanism by
      which HIV-1 causes cell death in activated CD4 T lymphocytes. We showed that
      proviral DNA integration triggers DNA-PK dependent death signaling, leading to
      p53 phosphorylation and cell demise (Cooper A et al. Nature 498:376-379, 2013).
      They have raised several hypothetical points that we further clarify here.

PMID- 24321565
TI  - Crohn's disease: a review of treatment options and current research.
AB  - Crohn's disease is an autoimmune disorder that affects nearly 1.4 million
      Americans. The etiology of Crohn's disease is not completely understood, however,
      research has suggested a genetic link. There is currently no known cure for
      Crohn's disease and, as a result, most government-funded research is being
      conducted to increase the quality of life of afflicted patients (i.e. reducing
      chronic inflammation and alleviating growth impairment in pediatric patients). A
      number of treatment options are available including an alpha-4 integrin inhibitor
      and several TNF-alpha inhibitors. Furthermore, research is being conducted on
      several alternative treatment options to help understand exactly which cellular
      mechanisms (i.e. inducing apoptosis in leukocytes) are required for clinical
      efficacy. This review seeks to chronicle the current available treatment options
      for patients affected by Crohn's disease to aid in understanding potential
      cellular mechanistic requirements for an efficacious drug, and shed light on
      potential options for future treatment. 

PMID- 24321566
TI  - Estrogen attenuates lipopolysaccharide-induced nitric oxide production in
      macrophages partially via the nongenomic pathway.
AB  - Steroid hormones exert genotropic effects through members of the nuclear hormone
      receptor family. In the present study, we examined the effects of 17beta
      estradiol (E2) on nitric oxide (NO) production following lipopolysaccharide (LPS)
      stimulation and investigated the mechanisms in mouse bone marrow-derived
      macrophages (BMMs). E2 alone did not affect NO production. In contrast, E2
      inhibited LPS-induced production of NO in BMMs. Using a cell-impermeable E2
      conjugated to BSA (E2-BSA), which has been used to investigate the nongenomic
      effects of estrogen, we found that the increase in NO production induced by LPS
      was also attenuated. In addition, the intracellular estrogen receptor blocker,
      ICI 182780, only partially antagonized the total effects of E2 on LPS-stimulated
      NO production capacity. E2 also attenuated the LPS activation of p38 mitogen
      activated protein kinase (MAPK) but not that of extracellular-regulated protein
      kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK). This attenuation was not
      abrogated by ICI 182780. Moreover, the p38 inhibitor, SB 203580, greatly reduced
      the LPS-induced NO production, and the remaining NO levels were no longer
      regulated by E2. Additionally, E2-BSA inhibited LPS-mediated changes in p38 MAPK
      activation to the same extent as E2. Moreover, E2 and E2-BSA inhibited LPS
      induced activation of nuclear factor-kappa B (NF-kappaB) and activator protein 1
      (AP-1). This inhibitory effect of E2 was only partially antagonized by ICI
      182780. Taken together, these results suggest that E2 has an inhibitory effect on
      LPS-induced NO production in BMMs through inhibition of p38 MAPK phosphorylation,
      and blockade of NF-kappaB and AP-1 activation. These effects are mediated at
      least in part via a nongenomic pathway. 

PMID- 24321567
TI  - Late perforation at the jejuno-jejunal anastomosis after laparoscopic gastric
      bypass for morbid obesity.
AB  - BACKGROUND: Although marginal ulceration and perforation at the gastrojejunal
      anastomosis is an established, albeit rare, risk after laparoscopic Roux-en-Y
      gastric bypass (LRYGB) for morbid obesity, little is known about the risk of late
      perforation at the jejuno-jejunal (J-J) anastomosis. The objective of this study
      was to identify the incidence of J-J perforation and describe management options
      and sequelae. METHODS: This is a retrospective review of the database of all
      patients who underwent LRYGB. The results are presented as mean (range) where
      appropriate. RESULTS: Between April 2002 and April 2012, 1652 patients underwent
      LRYGB (1577 primary and 75 revision procedures). The operative mortality was
      .18%. Three patients developed late perforation of the J-J anastomosis (.18%) at
      7, 9, and 18 weeks, respectively. Two patients were managed with resection and
      reanastomosis of the perforation by laparotomy, and a third patient was managed
      laparoscopically with peritoneal lavage and transcutaneous tube jejunostomy of
      the perforation. All patients recovered well postoperatively. However, the third
      patient represented 42 days later with sepsis and died secondary to recurrent J-J
      ulcer perforation. CONCLUSION: Perforation of the J-J anastomosis is a rare and
      life-threatening delayed complication after LRYGB and usually presents within 2-8
      months postoperatively. It poses difficulties with diagnosis and management and
      should be dealt with judiciously.

PMID- 24321568
TI  - Comment on: Is there a relation between number of adjustments and results after
      gastric banding?

PMID- 24321569
TI  - Laparoscopic gastric plication versus mini-gastric bypass surgery in the
      treatment of morbid obesity: a randomized clinical trial.
AB  - BACKGROUND: Laparoscopic gastric plication (LGP) is emerging as a safe and
      effective bariatric procedure. However, there are no reports on the comparison
      between the efficacy and complications of LGP and laparoscopic mini-gastric
      bypass (LMGB), which is still an investigational bariatric procedure. The
      objective of this study was to compare safety and efficacy of LGP and LMGB in the
      treatment of morbid obesity in a one-year follow-up study. METHODS: Forty
      patients met the National Institutes of Health criteria and were randomly
      assigned to receive either LGP (n = 20) or LMGB (n = 20) by a block randomization
      method. Early and late complications, body mass index (BMI), excess weight loss,
      and obesity-related co-morbidities were determined at the 1-year follow-up.
      RESULTS: Operative time and mean length of hospitalization were shorter in the
      LGP group (71.0 minutes versus 125.0 minutes, P<.001, and 1.6 days versus 5.2
      days; P<.001, respectively). The mean percentage of excess weight loss (%EWL) at
      12 months follow-up was 66.9% in the LMGB group and 60.8% in the LGP group (P =
      .34). Improvement was observed in all co-morbidities in both groups, with the
      exception of hyperlipidemia, which remained unresolved in 4 patients. Lower
      incidence of iron deficiency occurred in the LGP group (P = .035).
      Rehospitalization and reoperation were not required in any cases. Considering the
      cost of instruments used in the LMGB procedure and operative time, LGP saved
      approximately $2,500 per case compared with LMGB. CONCLUSION: Both LGP and LMGB
      are effective weight loss procedures. LGP proved to be a simpler and less costly
      procedure compared with LMGB with a lower risk of iron deficiency during a 1-year
      follow-up study.

PMID- 24321570
TI  - Protein and amino acid status before and after bariatric surgery: a 12-month
      follow-up study.
AB  - BACKGROUND: Patients with obesity submitted to bariatric surgery present altered
      ingestion of macronutrient and micronutrient levels and nutrients deficiency. The
      objective of this study was to evaluate the protein and amino acid nutritional
      status of obese adults before and after bariatric surgery, with emphasis on
      plasma free amino acids. METHODS: Thirty obese women were submitted to Roux-en-Y
      gastric shunt (bariatric surgery). Food and protein intake, anthropometric and
      bioimpedance data (body composition analysis), and serum total protein, albumin,
      and plasma amino acids levels were collected before the surgery (preoperative)
      and 3, 6, and 12 months after the surgical procedure. RESULTS: The mean protein
      intake was 47+/-2 g/day. The total weight loss during the study period was 39+/-8
      kg; the fat-free mass decreased 7+/-5 kg. The amino acid profile showed increased
      concentrations of most amino acids 3 months after surgery; at 6 months, glutamic
      acid, serine, arginine, alanine, methionine, valine, phenylalanine, isoleucine,
      and tyrosine concentrations decreased. The total protein and albumin
      concentrations dropped along the 12-month follow-up. CONCLUSION: The amino acid
      profile changes after RYGB are evidence that total protein and albumin levels may
      not be good indicators of protein profile after the surgery.

PMID- 24321571
TI  - Weight regain after Roux-en-Y gastric bypass: loss of restriction?

PMID- 24321573
TI  - Loneliness and Facebook motives in adolescence: a longitudinal inquiry into
      directionality of effect.
AB  - The increasing popularity of Facebook among adolescents has stimulated research
      to investigate the relationship between Facebook use and loneliness, which is
      particularly prevalent in adolescence. The aim of the present study was to
      improve our understanding of the relationship between Facebook use and
      loneliness. Specifically, we examined how Facebook motives and two relationship
      specific forms of adolescent loneliness are associated longitudinally. Cross
      lagged analysis based on data from 256 adolescents (64% girls, M(age) = 15.88
      years) revealed that peer-related loneliness was related over time to using
      Facebook for social skills compensation, reducing feelings of loneliness, and
      having interpersonal contact. Facebook use for making new friends reduced peer
      related loneliness over time, whereas Facebook use for social skills compensation
      increased peer-related loneliness over time. Hence, depending on adolescents'
      Facebook motives, either the displacement or the stimulation hypothesis is
      supported. Implications and suggestions for future research are discussed.

PMID- 24321574
TI  - Effects of acute exposures to mecoprop, mecoprop-p and their biodegradation
      product (2-MCP) on the larval stages of the Pacific oyster, Crassostrea gigas.
AB  - Studies have shown that pesticides are sometimes detected at rather high levels
      in seawater and it has been suggested that these chemical compounds could act as
      additional stress factor for oysters cultured in coastal environments. The
      effects of pesticides on marine molluscs could be particularly harmful in the
      early stages which correspond to critical life stages. This study aimed to assess
      the effects of mecoprop, mecoprop-p and their degradation compound 2-methyl-4
      chlorophenol on two larval stages of Crassostrea gigas. Embryotoxic effects were
      assessed on veliger larvae after 36 h exposures, and both percentages of normal
      larvae and types of abnormalities were taken into account. The effects of the
      three substances were evaluated on 21-day-old pediveliger larvae by calculating
      metamorphosis rates after 24h exposures. The results of the embryotoxicity assay
      indicated that 2-methyl-4-chlorophenol was more toxic (EC50: 10.81 mg L(-1)) than
      its parent compounds (EC50 mecoprop: 42.55 mg L(-1); EC50 mecoprop-p: 78.85 mg L(
      1)). Mecoprop in particular injured shell formation with an increase of shell
      abnormalities following herbicide concentrations. The active substances were not
      toxic to metamorphosis processes, but 2-MCP was revealed to be more toxic to the
      success of metamorphosis (EC50: 7.20 mg L(-1)) than to embryo-larval development.
      However, the toxic concentrations were several orders of magnitude higher than
      environmental concentrations.

PMID- 24321575
TI  - Is arsenic biotransformation a detoxification mechanism for microorganisms?
AB  - Arsenic (As) is extremely toxic to living organisms at high concentration. In
      aquatic systems, As exists in different chemical forms. The two major inorganic
      As (iAs) species are As(V), which is thermodynamically stable in oxic waters, and
      As(III), which is predominant in anoxic conditions. Photosynthetic microorganisms
      (e.g., phytoplankton and cyanobacteria) take up As(V), biotransform it to
      As(III), then biomethylate it to methylarsenic (MetAs) forms. Although As(III) is
      more toxic than As(V), As(III) is much more easily excreted from the cells than
      As(V). Therefore, majority of researchers consider the reduction of As(V) to
      As(III) as a detoxification process. The biomethylation process results in the
      conversion of toxic iAs to the less toxic pentavalent MetAs forms
      (monomethylarsonate; MMA(V), dimethylarsonate; DMA(V), and trimethylarsenic
      oxide; TMAO(V)) and trimethylarsine (TMAO(III)). However, biomethylation by
      microorganisms also produces monomethylarsenite (MMA(III)) and dimethylarsenite
      (DMA(III)), which are more toxic than iAs, as a result of biomethylation by the
      microorganisms, demonstrates the need to reconsider to what extent As
      biomethylation contributes to a detoxification process. In this review, we
      focused on the discussion of whether the biotransformation of As species in
      microorganisms is really a detoxification process with recent data. 

PMID- 24321576
TI  - Berberine metabolites could induce low density lipoprotein receptor up-regulation
      to exert lipid-lowering effects in human hepatoma cells.
AB  - Berberine (BBR) is an isoquinoline alkaloid isolated from several Chinese herbal
      medicines, such as Coptis chinensis, Berberis aristata, and Coptis japonica. It
      exhibits a lipid-lowering effect by up-regulating the hepatic low density
      lipoprotein receptor (LDLR) expression. However, the plasma concentration of BBR
      is very low after oral administration for the reason that BBR is poorly absorbed
      and rapidly metabolized. Therefore, it is hard to explain the pharmacological
      effects of BBR in vivo. Here, RT-PCR, Western blotting and Oil Red O staining
      were used to investigate the effects of four BBR metabolites on LDLR expression
      and lipid accumulation in human hepatoma Hep G2 cells. Our results suggested that
      BBR increased the LDLR mRNA and protein levels in a time- and dose-dependent
      manner. Four metabolites of BBR, jatrorrhizine, columbamine, berberrubine and
      demethyleneberberine, were found to be able to up-regulate LDLR mRNA and protein
      expression. Moreover, almost all the metabolites had potent effects on inhibiting
      cellular lipid accumulation. These results suggest that both BBR and its
      metabolites exhibit lipid-lowering effects by up-regulating LDLR expression, and
      BBR and its metabolites might be the in vivo active forms of BBR produced after
      oral administration. This study provides information to help us understand the
      mechanisms underlying the hypolipidemic effects of BBR in vivo. 

PMID- 24321577
TI  - Iridoid and phenylpropanoid glycosides from Scrophularia ningpoensis Hemsl. and
      their alpha-glucosidase inhibitory activities.
AB  - A new phenylpropanoid glycoside, designated Scrophuside (1) and two new iridoid
      glycosides, respectively named Ningposide I (2) and Ningposide II (3), along with
      twelve known (4-15) iridoid and phenylpropanoid glycosides were obtained from the
      roots of Scrophularia ningpoensis Hemsl. by various chromatographic techniques
      and their structures were established through chemical methods and spectroscopic
      analyses. Most of the obtained compounds have been screened for alpha-Glucosidase
      inhibitory activity, in which compounds 4, 5, 7, 11, 12, 13, and 14 show
      significant activity. 

PMID- 24321578
TI  - Effective isolation protocol for secondary metabolites from saffron: semi
      preparative scale preparation of crocin-1 and trans-crocetin.
AB  - Extracts from saffron, the dried stigmata from Crocus sativus L. are recognized
      as valuable tools for pharmaceutical development in neuroprotection and
      antidepressive therapy. One major lead compound is crocin-1 (1), which gets
      metabolized to the C20-dicarboxylic acid trans-crocetin (2) being responsible for
      potential NMDA-antagonistic effects in the central nervous system. Neither crocin
      1 nor crocetin are commercially available in sufficient quality and to a
      reasonable price. The following protocol describes effective methods to obtain
      both compounds from an EtOH-water extract (2:8) in good yields (about 43% related
      to the starting material). Crocin-1 (purity>90%) can be obtained from the extract
      by means of partition chromatography (FCPC) in a single run without fractionation
      of the mobile phase by using only the stationary phase and in yields of about
      48%, related to the saffron extract. Trans-crocetin can be obtained from the EtOH
      water extract by enzymatic deglycosylation of crocins using commercially
      available cheap glycosidase mixtures as e.g. Rohm Enzyme(r) or RohamentCL(r).
      Further polishing can be achieved by flash chromatography on MCI(r) stationary
      phase with yields between 6 and 11%. The protocols described provide effective
      isolation of crocin-1 and trans-crocetin reference compounds for further
      preclinical and analytical studies with saffron extracts. 

PMID- 24321579
TI  - Oleanane type glycosides from Paronychia anatolica subsp. balansae.
AB  - Four new oleanane-type triterpene glycosides were isolated from the methanol
      extract of the roots of Paronychia anatolica subsp. balansae along with three
      known oleanane-type triterpene glycosides. Structures of the new compounds were
      established as 3-O-beta-D-glucuronopyranosyl-28-O-[alpha-L-rhamnopyranosyl-(1->2)
      beta-D-quinovopyranoside] zahnic acid, 3-O-beta-D-glucuronopyranosyl-28-O-[beta-D
      xylopyranosyl-(1->4)-alpha-L-rhamnopyranosyl-(1->2)-beta-D-quinovopyranoside]
      zahnic acid, 3-O-beta-D-glucuronopyranosyl-28-O-[alpha-L-arabinofuranosyl-(1->2)
      beta-D-quinovopyranoside] zahnic acid, 28-O-[alpha-L-rhamnopyranosyl-(1->4)-beta
      D-glucopyranosyl-(1->6)-beta-D-glucopyranosyl]-medicagenic acid, by using 1D and
      2D-NMR techniques and mass spectrometry. The cytotoxic activity of the isolated
      compounds was evaluated against a small panel of cancer cell lines including
      human breast cancer (MCF-7), human lung adenocarcinoma (A549) and human leukemia
      (U937) cell lines.

PMID- 24321580
TI  - Three pairs of variecolortide enantiomers from Eurotium sp. with caspase-3
      inhibitory activity.
AB  - 7-O-methylvariecolortide A (1), variecolortide B (2), and variecolortide C (3),
      the rare variecolortides existing in racemic manner, were isolated from an
      endolichenic fungal strain Eurotium sp. (No. 17-11-8-1). With the chiral HPLC
      technology, (-)-(S)-7-O-methylvariecolortide A (1a), (+)-(R)-7-O
      methylvariecolortide A (1b), (-)-(S)-variecolortide B (2a), (+)-(R)
      variecolortide B (2b), (-)-(S)-variecolortide C (3a), and (+)-(R)-variecolortide
      C (3b) were successfully separated and obtained. Their absolute configurations
      were firstly assigned by ECD experiment and ECD calculation. According to the
      relation of isolated compounds, a plausible biosynthetic pathway for
      variecolortides was proposed. In caspase-3 enzymatic assay, compounds 1-3 showed
      inhibitory activity, with IC50 values of 1.7, 0.8 and 15.7 MUM, respectively.

PMID- 24321581
TI  - Vinorelbine in pemetrexed-pretreated patients with malignant pleural
      mesothelioma.
AB  - BACKGROUND: Pemetrexed-platinum chemotherapy is the standard first-line treatment
      of unresectable malignant pleural mesothelioma (MPM). At progression, patients
      are generally selected to experimental trials, when available, or, in every-day
      clinical practice, they are offered second-line chemotherapy. The optimal
      treatment has not yet been defined. The aim of this retrospective, single-center
      study was to evaluate the activity and toxicity of vinorelbine administered to a
      consecutive series of pemetrexed-pretreated MPM patients. METHODS: Vinorelbine 25
      mg/m(2) was administered intravenously as a single agent on days 1, 8 every three
      weeks, either as second-line (2L) or further-line (>2L) therapy. Treatment was
      repeated for a maximum of 6 cycles, until progression, or unacceptable toxicity.
      RESULTS: Fifty-nine patients were included in this analysis. Vinorelbine was
      given to 34 patients as 2L, and to 25 as > 2L treatment. The median age was 69
      years (range 45-80). Forty-two patients (71.2%) had a good EORTC prognostic
      score. Partial response was observed in 9 (15.2%) cases, stable disease in 20
      (33.9%). The overall disease control rate (DCR) was 49.1%. Median progression
      free survival (PFS) and overall survival (OS) were 2.3 and 6.2 months,
      respectively. ECOG performance status (PS) (HR(0 vs. 1-2) 0.50; 95%CI: 0.3-0.8; p
      = 0.014) and PFS >= 6 months following first-line (FL) chemotherapy (HR(FL-PFS>6
      ms vs. <6 ms) 0.50; 95%CI: 0.3-0.9; p = 0.031) were significantly associated to
      OS in multivariate analysis. No difference was observed in terms of DCR, PFS, and
      OS in relation to age, histology, sex, line of vinorelbine therapy, or response
      to FL treatment. Hematological toxicity was acceptable, with grade 3/4
      neutropenia occurring in 5 (8.4%) patients, and there were no cases of febrile
      neutropenia. The main non-hematological toxicities were grade 2 fatigue in 17
      (28.8%) and constipation in 7 (11.8%) patients. CONCLUSIONS: Vinorelbine was
      moderately active in pemetrexed-pretreated MPM patients, with an acceptable
      toxicity profile, particularly in patients with ECOG-PS0 and FL-PFS >= 6 months.

PMID- 24321582
TI  - Correlation of the Voice Handicap Index-10 (VHI-10) and Voice-Related Quality of
      Life (V-RQOL) in patients with dysphonia.
AB  - OBJECTIVES: This study examines the correlation between two voice-specific
      patient-reported outcome measures: the Voice Handicap Index-10 (VHI-10) and Voice
      Related Quality of Life (V-RQOL). STUDY DESIGN: Retrospective chart review.
      PARTICIPANTS: Eight hundred four patients presenting to our voice clinic between
      May 2009 and August 2011. All patients completed the VHI-10 and V-RQOL in a
      single sitting. METHODS: Correlation between the two scales was examined using
      Spearman rank analysis. Calculated VHI-10 score was derived from V-RQOL score by
      direct conversion equation and compared with measured VHI-10 score. Receiver
      Operating Characteristic (ROC) curves were derived for diagnostic groups.
      RESULTS: Spearman correlation coefficient between the VHI-10 and V-RQOL was -0.91
      (P < 0.0001). VHI-10 and V-RQOL scores were also significantly correlated among
      diagnostic categories. Calculated and measured VHI-10 scores were significantly
      different both for individuals and overall. Area under the curve (AUC) values
      from ROC curves were significantly different for the presbyphonia (V-RQOL AUC =
      0.586 [standard error, SE +/- 0.033]; VHI-10 AUC = 0.530 [SE +/- 0.031]; P =
      0.0014) and muscle tension dysphonia (V-RQOL AUC = 0.536 [SE +/- 0.026]; VHI-10
      AUC = 0.508 [SE +/- 0.26]; P = 0.018) groups, with the V-RQOL showing relatively
      greater sensitivity. CONCLUSIONS: The VHI-10 and V-RQOL are highly correlated.
      However, VHI-10 score cannot be calculated from V-RQOL score using the tested
      equation. The V-RQOL may be more sensitive than the VHI-10 in detecting the
      impact of presbyphonia and muscle tension dysphonia.

PMID- 24321583
TI  - Ambulatory phonation monitoring in a sample of 92 call center operators.
AB  - OBJECTIVES: The voice is a primary work tool for call center operators, but the
      main risk factors for voice disorders in this category have not yet been
      clarified. This study aimed to analyze the vocal behavior in call center
      operators and search for correlations between the daily voice dose and the self
      perceived voice-related handicap. STUDY DESIGN: Prospective. SUBJECTS AND
      METHODS: Ninety-two call center operators (aged 24-50 years) underwent ambulatory
      phonation monitoring during a working day and were administered the Voice
      Handicap Index (VHI) questionnaire and a questionnaire concerning smoking habits,
      symptoms, and extrawork activities requiring intensive voice use. RESULTS: Mean
      percentage phonation time (PT) during work was 14.74% and ranged from 4% to 31%.
      There was a significant difference between the percentage PT in working time and
      in extrawork time; however, subjects with high percentage PT in working time
      maintained a high value also in extrawork time. The mean PT was 87.5 +/- 35.8
      minutes and was not correlated with age, gender, number of work hours, symptoms,
      extraprofessional voice use, and VHI scores. The mean amplitude was significantly
      higher in subjects with longer PT and higher pitch (P < 0.001). VHI score (median
      = 9) was slightly higher than in the general population but not related to the
      number of work hours, indicating that work time was not a critical factor in
      causing the perception of voice problems. CONCLUSION: Our study provides data
      about the voice behavior of a large cohort of call center operators and
      demonstrates that the number of work hours and the percentage PT are not
      statistically related to the perception of voice disturbances in this working
      category.

PMID- 24321584
TI  - The effect of antireflux therapy on phonomicrosurgical outcomes: a preliminary
      retrospective study.
AB  - OBJECTIVE/HYPOTHESIS: Currently, no clinical standards exist with regard to
      antireflux medications in the perioperative period for patients undergoing
      surgery for benign vocal fold lesions. The present study sought to determine the
      clinical yield of these medications on operative outcomes in patients who
      underwent surgical treatment for benign vocal fold lesions. STUDY DESIGN:
      Retrospective, outcomes study. METHODS: Medical records were reviewed from a
      single surgeon database between January 2011 and June 2012 to quantify outcomes
      in patients taking antireflux medications compared with subjects not taking
      medications at the time of surgery. Voice Handicap Index (VHI)-10 and Reflux
      Symptom Index (RSI) scores were the primary dependent variables. The t test
      analyses were conducted to compare VHI-10 and RSI scores. Additional multivariate
      regression analyses were conducted to evaluate medication effects on VHI and RSI,
      adjusting for potential confounds. RESULTS: A total of 51 patients met inclusion
      criteria. Of these patients, 12 (23.5%) were using antireflux medication(s) at
      the time of surgery and 39 (76.5%) were not. The mean shifts in VHI-10 and RSI
      after surgery for the antireflux therapy (ART) group were -14.75 and -7.5,
      respectively. For the non-antireflux therapy (non-ART) group, mean DeltaVHI-10
      and DeltaRSI values were -9.87 and -5.05, respectively. Both t test and
      regression analyses confirmed no statistical difference between the ART and non
      ART groups for both DeltaVHI-10 and DeltaRSI. Additional regression analysis
      revealed a positive correlation between preoperative RSI score and DeltaRSI
      score. CONCLUSION: Antireflux medications did not significantly alter
      postoperative outcomes in this preliminary cohort of patients.

PMID- 24321585
TI  - The Amatsu's tracheoesophageal shunt: analysis of 84 cases.
AB  - INTRODUCTION: Amatsu's tracheoesophageal shunt can be indicated for vocal
      rehabilitation in candidates to total laryngectomy. It is performed in the period
      of the procedure of total laryngectomy and has been indicated due to its
      technical facility, exemption from the use of voice prosthesis, and lack of
      additional costs for its maintenance. OBJECTIVE: To evaluate the results obtained
      with the Amatsu's tracheoesophageal shunt, along 14 years of experience, in two
      Brazilian hospitals. STUDY DESIGN: Clinical retrospective. MATERIAL AND METHOD:
      From 1991 to 2005, eighty-four patients were submitted to the Amatsu's
      tracheoesophageal shunt. Seventy-seven (91.7%) were male and seven (8.3%) female,
      aged between 30 and 82 years, mean age of 57.5 years, and an average age of 52
      years. All patients had squamous cell carcinoma of larynx and/or hypopharynx.
      Sixty-eight (81.0%) were stage III or IV. They were submitted to total
      laryngectomy and the Amatsu's tracheoesophageal shunt was performed during the
      tumor removal surgery. The following variables were analyzed: acquisition of
      intelligible speech, vocal recovery time after surgery, and the occurrence of
      specific surgical complications of the shunt (pulmonary aspiration). RESULTS:
      Seventy-six patients were evaluated with respect to the effectiveness of the
      technique. Fifty-three patients (70.0%) presented vocalization by the shunt; in
      46 patients (60.5%), the speech was fully intelligible. The time required for
      restoration of speech was 12-87 postoperative days. Of the 83 patients evaluated
      in relation to the development of complications, 25 (30.1%) presented aspiration
      by the shunt during oral ingestion. In 23 patients (27.7%), the aspiration was
      managed conservatively without complications. Two patients (2.4%) required
      surgical closure of the shunt due to intractable aspiration. CONCLUSION: Vocal
      rehabilitation with the Amatsu's tracheoesophageal shunt is effective in most
      patients who underwent total laryngectomy. It can be evidenced by the acquisition
      of intelligible speech in most patients. The aspiration, although often, is not
      shown to be a limiting complication.

PMID- 24321586
TI  - Correlation between the length and sagittal projection of the upper and lower jaw
      and the fundamental frequency.
AB  - OBJECTIVE: To report on the correlation between the length and projection of the
      upper and lower jaw and the fundamental frequency (F0). STUDY DESIGN: Prospective
      study. MATERIALS AND METHODS: A total of 45 healthy subjects were included in
      this study. The facial skeletal measurements included: SNA, SNB, ANB, angles that
      reflect the position of the maxilla and mandible in relation to the base of skull
      and to each others, length of mandible Co-Gn, and length of maxilla PNS-ANS. All
      subjects underwent acoustic analysis using VISI-PITCH IV. RESULTS: The means for
      F0 and habitual frequency were 220.75 + 40.01 Hz and 216.99 + 43.9 Hz,
      respectively. The means for SNA, SNB, and ANB were 80.753 +/- 3.20, 77.409 +/-
      3.64, and 3.336 +/- 2.57, respectively. The mean length of the mandible and
      maxilla were 104.28 + 7.94 and 50.29 + 3.94, respectively. In the total group,
      there was a moderate negative correlation between F0 and habitual frequency and
      the length of the mandible (r = -0.528 and -0.577, respectively). There was also
      a moderate negative correlation between F0 and habitual frequency and the length
      of the maxilla (r = -0.473 and -0.519, respectively). Similar findings were
      present after excluding the pubertal subjects. With respect to the other
      cephalometric measurements, the correlation was poor (r value < 0.3).
      CONCLUSIONS: There is a moderate negative correlation between the length of the
      upper and lower jaw and the average F0 and habitual frequency. The remaining
      facial sagittal projection parameters do not correlate with the average F0 and
      habitual frequency.

PMID- 24321587
TI  - Dysphonia in performers: toward a clinical definition of laryngology of the
      performing voice.
AB  - OBJECTIVES: To identify causes of dysphonia in performers and compare causes and
      aspects of treatment of dysphonia in performers and nonperformers. STUDY DESIGN:
      Case-control study. METHODS: A chart review of all new patients presenting with a
      chief complaint of dysphonia over a 1-year period was performed. The prevalence
      of laryngeal disorders was reviewed and differences between performers and
      nonperformers were analyzed. The odds ratio of the prevalence of each disorder
      was computed against performer status as a risk factor. RESULTS: Four hundred
      seventy-six new patients complaining of dysphonia presented over 12 months; 74
      were vocal performers. The median duration of symptoms in performers was 90 days.
      Phonotraumatic lesions were significantly more prevalent in performers (63.5% vs.
      28.6%, P < 0.001), particularly bilateral mid-fold swelling (4-fold increase in
      performers), pseudocysts (3-fold increase), and vocal fold hemorrhage/ectasia.
      Neurologic disorders (vocal fold paralysis and spasmodic dysphonia), neoplastic
      pathologies, and age-related phenomena (atrophy/presbyphonia) were significantly
      more common in nonperformers. Overall and diagnosis-specific rates of surgical
      intervention were equal between the two groups. CONCLUSIONS: Phonotraumatic
      injury is responsible for the majority of dysphonia in vocal performers, to a
      significantly greater extent than in nonperformers and requires the
      implementation of standard therapeutic strategies. Awareness of the specific
      risks and management needs of the performer is of paramount importance to the
      practice of laryngology of the performing voice.

PMID- 24321588
TI  - Inflammatory myofibroblastic tumor of the larynx-a case report.
AB  - OBJECTIVES: Inflammatory myofibroblastic tumor (IMT) is a borderline neoplasm
      with uncertain malignant potential. It is a rare disease also referred to as an
      inflammatory pseudotumor, a plasma cell granuloma, and an inflammatory
      fibrosarcoma. IMT rarely also involves the head and neck region with only 50
      cases of laryngeal IMT reported in the literature, and this is the first case
      with reported magnetic resonance imaging (MRI) findings. METHODS: A 37-year-old
      man with a 1-year history of hoarseness, dysphagia, and fatigue presented with a
      right vocal fold submucosal mass and was treated conservatively. RESULTS: The MRI
      of the neck revealed a mildly spontaneously hyperintense right true vocal fold on
      GRE images and relative hyperintensity on fat-saturation T2-weighted images. A
      biopsy of the right-sided submucosal laryngeal mass was performed and the
      pathologic examination revealed a lesion consistent with an IMT. CONCLUSION: IMT
      is a borderline neoplasm with uncertain malignant potential. There are many
      variants of IMT and its etiology is not truly understood. In general, IMT of the
      larynx has a benign clinical course with low rates of recurrence.

PMID- 24321589
TI  - Scanning electron microscopy of the tongue, pharynx, and larynx of rats exposed
      to cigarette smoke.
AB  - OBJECTIVE: To examine, by using scanning electron microscopy, the surface of the
      tongue, pharynx, and larynx of animals exposed to tobacco. STUDY DESIGN:
      Experimental study. METHODS: Twenty rats were allocated to two groups: group I,
      control group: 10 rats not exposed to any inhaling pollutant and group II,
      tobacco group: 10 rats exposed to smoke from 10 cigarettes twice a day for 260
      days. Animals of both groups had no restriction of food or water. After those 260
      days, their aerodigestive segment was removed, and fragments of their tongue,
      hypopharynx, and right vocal fold were immersed in 2.5% glutaraldehyde and
      prepared for scanning electron microscopy. RESULTS: The filiform tongue papillae
      of the tobacco group were irregularly displayed, flattened, and adhered to each
      other. The hypopharynx mucosa was highly irregular, thickened, rough and had
      increased superficial peeling. The mucosa of the vocal folds had deep furrows
      surrounding the cells. These alterations were not identified for the control
      group. CONCLUSION: Several changes were recorded for the tongue, pharynx, and
      larynx of tobacco group animals, confirming the harmful effects of smoking to the
      respiratory and digestive epithelium.

PMID- 24321590
TI  - Aerodynamic and acoustic effects of ventricular gap.
AB  - PURPOSE: Supraglottic compression is frequently observed in individuals with
      dysphonia. It is commonly interpreted as an indication of excessive
      circumlaryngeal muscular tension and ventricular medialization. The purpose of
      this study was to describe the aerodynamic and acoustic impact of varying
      ventricular medialization in a canine model. METHODS: Subglottal air pressure,
      glottal airflow, electroglottograph, acoustic signals, and high-speed video
      images were recorded in seven excised canine larynges mounted in vitro for
      laryngeal vibratory experimentation. The degree of gap between the ventricular
      folds was adjusted and measured using sutures and weights. Data were recorded
      during phonation when the ventricular gap was narrow, neutral, and large. Glottal
      resistance was estimated by measures of subglottal pressure and glottal flow.
      RESULTS: Glottal resistance increased systematically as ventricular gap became
      smaller. Wide ventricular gaps were associated with increases in fundamental
      frequency and decreases in glottal resistance. Sound pressure level did not
      appear to be impacted by the adjustments in ventricular gap used in this
      research. CONCLUSIONS: Increases in supraglottic compression and associated
      reduced ventricular width may be observed in a variety of disorders that affect
      voice quality. Ventricular compression may interact with true vocal fold posture
      and vibration resulting in predictable changes in aerodynamic, physiological,
      acoustic, and perceptual measures of phonation. The data from this report
      supports the theory that narrow ventricular gaps may be associated with
      disordered phonation. In vitro and in vivo human data are needed to further test
      this association.

PMID- 24321591
TI  - Effects of septoplasty on speech and voice.
AB  - OBJECTIVES: The aim of this study was subjective and objective evaluation of
      changes in acoustic features of voice before and after septoplasty surgery. STUDY
      DESIGN: Prospective. METHODS: Twenty patients scheduled for septoplasty procedure
      were included in the study. Before and 1 and 3 months after septoplasty surgery,
      acoustic analysis were performed. The recordings of /a/ vowel were used to
      evaluate average fundamental frequency (F0), Jitter percent, and Shimmer percent.
      In spectrographic analyses, F3-F4 values for the vowels /i, e, a, o, and u/,
      nasal formant frequencies of the consonants /m/ and /n/ in the word /mana/, and
      four formant frequencies (F1, F2, F3, and F4) for nasalized /a/ vowel following a
      nasal consonant /n/ in the word /mana/ were compared. For the perceptual
      evaluation, the patients were asked to read the Turkish "Dere" passage. The
      differences in nasal resonance and subjective evaluations were rated. RESULTS: A
      statistically significant change was not observed in F0 (P=0.307), Jitter
      (P=0.919), and Shimmer (P=0.024) values measured before and after the operation
      for vowel /a/. Nasal formants measured before and after the operation for nasal
      formant /m/ and nasal formant /n/ in the word /mana/, which contains nasal
      consonants, and nasalized vowel /a/, which comes after a nasal consonant, did not
      differ statistically significant (P=0.096 and P=0.034, respectively). Comparisons
      among F1, F2, F3, and F4 values did not reveal a statistically significant change
      for nasalized vowel /a/, which comes after a nasal consonant in the word /mana/.
      CONCLUSIONS: Our study shows that a complete therapeutic approach to patients
      affected by nasal septum deviation do not reveal significant voice abnormalities.

PMID- 24321592
TI  - Can pharmacological and psychological treatment change brain structure and
      function in PTSD? A systematic review.
AB  - While there is evidence of clinical improvement of posttraumatic stress disorder
      (PTSD) with treatment, its neural underpinnings are insufficiently clear.
      Moreover, it is unknown whether similar neurophysiological changes occur in PTSD
      specifically after child abuse, given its enduring nature and the developmental
      vulnerability of the brain during childhood. We systematically reviewed PTSD
      treatment effect studies on structural and functional brain changes from PubMed,
      EMBASE, PsycINFO, PILOTS and the Cochrane Library. We included studies on adults
      with (partial) PTSD in Randomized Controlled Trials (RCT) or pre-post designs
      (excluding case studies) on pharmacotherapy and psychotherapy. Risk of bias was
      evaluated independently by two raters. Brain coordinates and effect sizes were
      standardized for comparability. We included 15 studies (6 RCTs, 9 pre-post), four
      of which were on child abuse. Results showed that pharmacotherapy improved
      structural abnormalities (i.e., increased hippocampus volume) in both adult
      trauma and child abuse related PTSD (3 pre-post studies). Functional changes were
      found to distinguish between groups. Adult-trauma PTSD patients showed decreased
      amygdala and increased dorsolateral prefrontal activations post-treatment (4
      RCTs, 5 pre-post studies). In one RCT, child abuse patients showed no changes in
      the amygdala, but decreased dorsolateral prefrontal, dorsal anterior cingulate
      and insula activation post-treatment. In conclusion, pharmacotherapy may reduce
      structural abnormalities in PTSD, while psychotherapy may decrease amygdala
      activity and increase prefrontal, dorsal anterior cingulate and hippocampus
      activations, that may relate to extinction learning and re-appraisal. There is
      some evidence for a distinct activation pattern in child abuse patients, which
      clearly awaits further empirical testing. 

PMID- 24321593
TI  - The impact of automated filtering of BLAST-determined homologs in the
      phylogenetic detection of horizontal gene transfer from a transcriptome assembly.
AB  - Phylomes (comprehensive sets of gene phylogenies for organisms) are built to
      investigate fundamental questions in genomics and evolutionary biology, such as
      those pertaining to the detection and characterization of horizontal gene
      transfer in microbes. To address these questions, phylome construction demands
      rigorous yet efficient phylogenetic methods. Currently, many sequence alignment
      and tree-building models can analyze several thousands of genes in a high
      throughput manner. However, the phylogenetics is complicated by variability in
      sequence divergence and different taxon sampling among genes. In addition,
      homolog selection for automated approaches often relies on arbitrary sequence
      similarity thresholds that are likely inappropriate for all genes in a genome. To
      investigate the effects of automated homolog selection on the detection of
      horizontal gene transfer using phylogenomics, we constructed the phylome of a
      transcriptome assembly of Alexandrium tamarense, a microbial eukaryote with a
      history of horizontal and endosymbiotic gene transfer, using seven sequence
      similarity thresholds for selecting putative homologs to be included in
      phylogenetic analyses. We show that no single threshold recovered informative
      trees for the majority of A. tamarense unigenes compared to the pooled results
      from all pipeline iterations. As much as 29% of trees built could have misleading
      phylogenetic relationships that appear biased in favor of those otherwise
      indicative of horizontal gene transfer. Perhaps worse, nearly half of the
      unigenes were represented by a single tree built at just one threshold, making it
      difficult to assess the validity of phylogenetic relationships recovered in these
      cases. However, combining the results from several pipeline iterations maximizes
      the number of informative phylogenies. Moreover, when the same phylogenetic
      relationship for a given unigene is recovered in multiple pipeline iterations,
      conclusions regarding gene origin are more robust to methodological artifact.
      Using these methods, the majority of A. tamarense unigenes showed evolutionary
      relationships indicative of vertical inheritance. Nevertheless, many other
      unigenes revealed diverse phylogenetic associations, suggestive of possible gene
      transfer. This analysis suggests that caution should be used when interpreting
      the results from phylogenetic pipelines implementing a single similarity
      threshold. Our approach is a practical method to mitigate the problems associated
      with automated sequence selection in phylogenomics. 

PMID- 24321594
TI  - Ecology limits the diversity of the Cape flora: phylogenetics and diversification
      of the genus Tetraria.
AB  - Understanding the ecology and evolution of the hyper-diverse Cape flora is
      dependent on developing an understanding of its component parts, best epitomized
      by the Cape floral clades that have diversified and are largely endemic to the
      region. Here we employ a new dated phylogenetic hypothesis for the sedge genus
      Tetraria, one of the smaller Cape floral clades, to develop an understanding of
      timing and rates of diversification in the group. Specifically, we test whether
      diversification in Tetraria slowed as the number of extant lineages increased,
      suggesting that available ecological niche space has become increasingly
      saturated through time. The radiation of Tetraria began approximately 18million
      years ago, concordant with that of many other Cape clades. Diversification rates
      in the genus showed no drastic shifts in response to major environmental changes,
      but declined as lineage diversity accumulated, indicative of ecological
      limitation on speciation rates. This allows the development of heuristic
      predictions about the composition of Tetraria assemblages at various spatial
      scales, and suggests that closely related species should either be ecologically
      differentiated or have non-overlapping geographic distributions. The question of
      whether ecological limitation of diversity is a common phenomenon in other Cape
      lineages has important implications for our understanding of the evolution and
      ecology of the contemporary Cape flora as a whole.

PMID- 24321595
TI  - Aberrant telomerase expression in the endometrium of infertile women with deep
      endometriosis.
AB  - BACKGROUND AND AIMS: Considering the complex cellular and molecular mechanisms
      involved in endometriosis formation and progression and the similarities
      concerning the association of endometriosis with tumorigenesis and metastasis, we
      hypothesized a possible relationship between telomerase and the
      development/progression of endometriosis. The present study aimed to evaluate the
      expression of telomerase in the endometrium and peritoneal endometriotic lesions
      from women with endometriosis and controls. METHODS: A case-control study was
      performed comprising 25 infertile women with endometriosis and 44 fertile women
      without endometriosis as controls. Samples of endometrium and endometriotic
      peritoneal lesions of the same patient were harvested in the late luteal phase of
      the cycle. The expression of hTERT and GAPDH genes was measured by mRNA using qRT
      PCR based on TaqMan methodology. Student t test was used to compare the values
      between the groups; p >0.05 was accepted as statistically significant. RESULTS:
      The mean expression of hTERT in the endometriosis group was significantly high
      when compared to the control group (1.24 +/- 4.67 vs. 0.31 +/- 1.10, p = 0.026).
      When the expression of hTERT was compared in relation to disease stage, the group
      of moderate/severe endometriosis showed increased expression in relation to
      control group (2.59 +/- 7.35 vs. 0.31 +/- 1.10, p = 0.026). Regarding
      endometriotic peritoneal lesions, only one 1/25 expressed hTERT mRNA. This
      patient had deep endometriosis. CONCLUSIONS: There was an association between the
      expression of telomerase (hTERT mRNA) and the genesis and progression of
      endometriosis.

PMID- 24321596
TI  - Plasma level of glucagon-like peptide 1 in obese Egyptians with normal and
      impaired glucose tolerance.
AB  - BACKGROUND AND AIMS: Low GLP-1 has been implicated in obesity and type 2
      diabetes. Some studies reported reduced post-prandial GLP-1 levels in type 2
      diabetics, whereas others reported GLP-1 levels not reduced in patients with
      impaired glucose tolerance (IGT) or type 2 diabetes. We undertook this study to
      evaluate the effect of obesity and pre-diabetes on GLP-1 levels in response to 75
      g oral glucose. METHODS: Eighty subjects comprised four groups: 20 control
      subjects (normal weight and normal glucose tolerance (NGT)), 20 obese with NGT,
      20 obese with impaired fasting glucose (IFG) and 20 obese with both IFG and
      impaired glucose tolerance (IGT). Laboratory tests included fasting blood glucose
      (FBG), 75 g glucose OGTT, fasting insulin and glucose-stimulated GLP-1 (30 min
      after 75 g glucose). Insulin resistance was quantified using HOMA-IR. RESULTS:
      GLP-1 levels were significantly decreased in obese subjects compared to controls
      (571.17 +/- 170.37 vs. 908.50 +/- 169.90 pg/mL, p <0.001) and it was negatively
      correlated with body mass index (BMI) and waist circumference in all studied
      groups. Levels of GLP-1 were negatively correlated with HOMA-IR in all obese
      groups (r = -0.75, p <0.001). No significant difference was found in GLP-1 levels
      between all obese subjects (611.50 +/- 187.96, 577.50 +/- 150.85, 524.50 +/-
      167.35 pg/mL respectively, p >0.05). Morbidly obese cases (n = 15) had a
      significantly higher fasting insulin (25.20 +/- 2.49 vs. 14 +/- 3.81 MUIU/ml),
      higher HOMA-IR (6.69 +/- 1.2 vs. 3.48 +/- 1.20), and lower GLP- 1 (212.0 +/-
      35.64 vs. 603.82 +/- 136.35 pg/mL) (p <0.001) compared to non-morbid obese cases
      (n = 45). CONCLUSIONS: Obesity reduces the GLP-1 levels. In insulin resistance,
      GLP-1 levels were reduced and it was related to the degree of insulin resistance.

PMID- 24321597
TI  - Ischemic preconditioning for cell-based therapy and tissue engineering.
AB  - Cell- and tissue-based therapies are innovative strategies to repair and
      regenerate injured hearts. Despite major advances achieved in optimizing these
      strategies in terms of cell source and delivery method, the clinical outcome of
      cell-based therapy remains unsatisfactory. The non-genetic approach of
      ischemic/hypoxic preconditioning to enhance cell- and tissue-based therapies has
      received much attention in recent years due to its non-invasive drug-free
      application. Here we discuss the current development of hypoxic/ischemic
      preconditioning to enhance stem cell-based cardiac repair and regeneration. 

PMID- 24321598
TI  - Ultrasound-assisted lipase-catalyzed synthesis of D-isoascorbyl palmitate:
      process optimization and Kinetic evaluation.
AB  - BACKGROUND: D-isoascorbic acid is a food antioxidant additive and used in
      accordance with Good Manufacturing Practice (GMP). High solubility in water
      (about 150 g/L at 25 degrees C) reduces its effectiveness in stabilizing fats and
      oils. Our research group had successfully synthesized D-isoascorbyl palmitate
      using immobilized lipase Novozym 435 as a biocatalyst. Low production efficiency
      of D-isoascorbyl palmitate is still a problem for industrial production due to
      the long reaction time of over 24 h. In the present work, ultrasonic treatment
      was applied for accelerating the reaction process. The operation parameters were
      optimized to obtain the maximum D-isoascorbyl palmitate conversion rate by using
      a 5-level-4-factor Central Composite Design (CCD) and Response Surface Methdology
      (RSM). The reaction apparent kinetic parameters under the ultrasound treatment
      and mechanical shaking conditions were also determined and compared. RESULTS:
      Results showed that ultrasound treatment decreased the reaction time by over 50%.
      D-isoascorbyl palmitate yielded to 94.32 +/- 0.17% and the productivity reached
      to 8.67 g L-1 h-1 under the optimized conditions as: 9% of enzyme load (w/w), 61
      degrees C of reaction temperature, 1:5 of D- isoascorbic-to-palmitic acid molar
      ratio, and 137 W of the ultrasound power. The immobilized lipase Novozym 435
      could be reused for 7 times with 65% of the remained D-isoascorbyl palmitate
      conversion rate. The reaction kinetics showed that the maximum apparent reaction
      rate (vmax) of the ultrasound-assisted reaction was 2.85 times higher than that
      of the mechanical shaking, which proved that ultrasound treatment significantly
      enhanced the reaction efficiency. CONCLUSION: A systematic study on ultrasound
      assisted enzymatic esterification for D-isoascorbyl palmitate production is
      reported. The results show a promising perspective of the ultrasound technique to
      reduce the reaction time and improve the production efficiency. The commercial D
      isoascorbyl palmitate synthesis will be potentially realized due to this
      ultrasound-promoted esters synthesis method.

PMID- 24321599
TI  - Intermediate term follow-up after a single-piece-acrylic intraocular lens
      implantation in the ciliary sulcus- a cross-sectional study.
AB  - BACKGROUND: Implantation of a single-piece-acrylic intraocular lens (SPA-IOL) in
      the ciliary sulcus during phacoemulsification complicated with posterior capsule
      tear (PCT) may be associated with severe complications. The purpose of this study
      was to report the efficacy and safety of sulcus implantation of a SPA-IOL,
      designed for both in-the-bag and sulcus positioning. METHODS: A prospective cross
      sectional study including 12 patients, who underwent phacoemulsification with PCT
      and sulcus implantation of SPA-IOL designed for both in-the-bag and sulcus
      positioning (Seelens AF, Hanita, Israel) between January 2009 and March 2012
      (follow-up 12-37 months). Preoperatively corrected distance visual acuity (CDVA),
      subjective refraction and intraocular pressure (IOP) were recorded. Postoperative
      evaluation included anamnesis for IOL edge symptoms and transient visual
      obscurations (TVO) along with CDVA, subjective refraction IOP, anterior segment
      biomicroscopy, gonioscopy, assessment of IOL centration, fundus biomicroscopy and
      spectral-domain optical coherence tomography of the macula. RESULTS:
      Preoperatively, mean CDVA was 0.84 +/- 0.60 LogMAR (Counting Finger-20/33)
      improving to 0.18 +/- 0.13 LogMAR (20/40-20/20) at last examination (p = 0.004),
      as all the patients gained better CDVA. Mean preoperative spherical equivalent
      was -0.2 +/- 2.5 Diopter (D) (-4.0D to +5.4D) reaching -1.9 +/- 0.9 (-4.0D to 
      0.6D) at last examination (p = 0.12). Mean preoperative refractive astigmatism
      magnitude was 1.0 +/- 0.6D (0.3D to 2.3D) changing to 1.1 +/- 1.0D (0.0D to 3.0D)
      at last examination (p = 0.88). Mean preoperative IOP was 14.7 +/- 3.2 mmHg (11
      23 mmHg) without medications reaching 15.9 +/- 3.3 mmHg (10-21 mmHg) at last
      follow up (p = 0.21). Postoperatively one patient required two medications for
      IOP control in his study and contralateral eyes. None of the patients had
      symptoms of IOL edge or TVO. There were no intraocular hemorrhages, inflammatory
      reactions, or pigment dispersion and the IOLs were well centered in all cases.
      Central foveal thickness was 280 +/- 33 MUm (193-310 MUm). CONCLUSIONS:
      Appropriately designed SPA-IOL may be implanted in the ciliary sulcus during
      phacoemulsification with PCT rather than switching to another backup IOL
      demanding wound enlargement.

PMID- 24321600
TI  - Intra-patient dose escalation in Ewing's sarcoma treated with vincristine,
      doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide: a
      retrospective review.
AB  - BACKGROUND: Data suggests that males experience less toxicity and poorer survival
      than females treated for Ewing's sarcoma. We instituted an intra-patient dose
      escalation (DE) policy with Vincristine/Doxorubicin/Cyclophosphamide (VDC)
      alternating with Ifosfamide/Etoposide (IE) based on hematological nadirs and
      report its feasibility and safety. METHODS: A retrospective review of adherence
      to DE guidelines and toxicities was conducted for patients who received DE with
      VDC/IE over 3 years at a single cancer center. Absolute neutrophil counts (ANC)
      was collected on days 8, 12 and 15 for cycles 1-6. DE of 10%/cycle was applied if
      ANC > 1.5*109/L and platelet > 100*109/L on all blood results. The primary
      endpoint was the proportion of patients who received appropriate DE. The
      secondary endpoint was to assess morbidity, changes in hematologic nadirs between
      gender and age and a comparison with a prior cohort of ESFT patients who did not
      receive DE. Gender comparisons were assessed via independent 2-sample t-tests
      assuming unequal variances. Within cycle changes in hematologic nadirs were
      assessed using repeated measures ANOVA. Relapse free survival and overall
      survival (OS) curves were estimated using the Kaplan-Meier method. RESULTS: 23
      patients were identified (mean age: 27; range 17-54). 91 decisions for DE were
      made (1 decision excluded because of progressive disease) with 90% concordance
      with guidelines. No adverse outcomes occurred as a result of the inappropriate
      escalation. Grade 3/4 febrile neutropenia (FN) during VDC and IE was 26.1% (6/23
      patients) and 17.4% respectively with no difference for those who were DE. Males
      were less neutropenic after C1 and C3 of VDC compared to females (P-value C1 =
      0.003; C3 = 0.005). VDC was associated with greater neutropenia on day 8 whereas
      IE had greater neutropenia on day 12 (P-value <0.001). During VDC, a non
      statistical difference in neutropenia was seen for individuals aged 15-25 (n =
      13) compared with older individuals (P-value = 0.09). OS comparison for those
      with localized disease with a prior cohort who were not DE showed similar
      outcomes (P-value = 0.37). CONCLUSIONS: DE is deliverable without increased
      adverse outcomes. Males have less myelosuppression during VDC, and should be
      especially considered for DE.

PMID- 24321601
TI  - Inactivation of dairy bacteriophages by commercial sanitizers and disinfectants.
AB  - Many commercial sanitizers and disinfectants have been used over the years to
      control microbial contamination but their efficacy on phages is often unknown.
      Here, 23 commercial chemical products, including 21 food-grade sanitizers were
      tested against virulent dairy phages. These food-grade chemicals included
      oxidizing agents, halogenated agents, alcohols, quaternary ammonium compounds,
      anionic acids, iodine-based acids, and an amphoteric chemical. Phage P008 was
      first exposed to each sanitizer for 2 and 15min at room temperature and at two
      different concentrations, namely the lowest and highest no-rinse sanitizing
      concentrations. Organic matter (whey or milk) was also added to the testing
      solutions. At the end of the exposure period, the test solution was neutralized
      and the number of infectious phages was determined by plaque assays. The five
      most efficient sanitizers against phage P008 (<4 log of inactivation) were then
      tested against virulent lactococcal phages P008, CB13, AF6, P1532 of the 936
      group, P001 (c2), Q54, and 1358 as well as Lactobacillus plantarum phage B1 and
      Streptococcus thermophilus phage 2972 using the same protocol. The oxidizing
      agents and the quaternary ammonium compounds were the most efficient against all
      phages although phages CB13 and P1532 were less sensitive to these chemicals than
      the other phages. This study may help in the selection of appropriate chemicals
      for controlling phage contamination in industrial factories and research
      laboratories. 

PMID- 24321602
TI  - Effects of gamma irradiation for inactivating Salmonella Typhimurium in peanut
      butter product during storage.
AB  - Three types (A, B, and C) of peanut butter product with different water
      activities (0.18, 0.39, and 0.65 aw) inoculated with a 3-strain mixture of
      Salmonella Typhimurium were subjected to gamma irradiation (60Co) treatment, with
      doses ranging from 0 to 3 kGy. The inactivation of S. Typhimurium in the 3 types
      of treated peanut butter product over a 14 day storage period and the influence
      of storage temperature at 4 (refrigerated) and 25  degrees C (ambient), and
      peanut butter product formulation were investigated. Three types of peanut butter
      product inoculated with S. Typhimurium to a level of ca. 6.6 log CFU/g and
      subjected to gamma irradiation experienced significant (p<0.05) reductions of 1.3
      to 1.9, 2.6 to 2.8, and 3.5 to 4.0 log CFU/g at doses of 1, 2, and 3 kGy,
      respectively. The time required to reduce S. Typhimurium in peanut butter product
      to undetectable levels was 14, 5, and 5 days at 25 degrees C after exposure to 3
      kGy for products A, B, and C, respectively, and 7 days at 25  degrees C following
      exposure to 2 kGy for product C. During storage at 4 and 25  degrees C, survival
      of S. Typhimurium was lowest in product C compared to products A and B. Water
      activity (a(w)) of peanut butter product was likely the most critical factor
      affecting pathogen survival. When a(w) is reduced, radiolysis of water is
      reduced, thereby decreasing antimicrobial action. Overall, death was more rapid
      at 25  degrees C versus 4  degrees C for all peanut butter products during 14 day
      storage. Following gamma irradiation, acid values of peanut butter product were
      not significantly different from the control, and general observations failed to
      detect changes in color and aroma, even though lightness observed using a
      colorimeter was slightly reduced on day 0. The use of gamma irradiation has
      potential in preventing spoilage of post-packaged food by destroying
      microorganisms and improving the safety and quality of foods without compromising
      sensory quality.

PMID- 24321603
TI  - Effects of chitosan from Cunninghamella elegans on virulence of post-harvest
      pathogenic fungi in table grapes (Vitis labrusca L.).
AB  - This study aimed to obtain chitosan (CHI) from Cunninghamella elegans cultivated
      in corn step liquid (CSL)-based medium under optimized conditions and to assess
      the efficacy of the obtained CHI in inhibiting Botrytis cinerea and Penicillium
      expansum in laboratory media and when applied as a coating on table grapes (Vitis
      labrusca L.). Moreover, the influence of CHI-based coatings on several physical,
      physicochemical and sensory characteristics of the fruits during storage was
      assessed. According to the surface response methodology, the best conditions for
      isolating CHI from C. elegans cultivated in CSL-medium yielded 8.8 g/100mL at pHs
      between 5.0 and 5.5 and at 180 rpm. CHI from C. elegans inhibited mycelial growth
      and spore germination and caused morphological changes in the spores of the
      tested fungal strains. The CHI coatings delayed the growth of the assayed fungal
      strains in artificially infected grapes. Applying a CHI coating preserved the
      quality of grapes, as measured by some physical, physicochemical and sensory
      attributes, throughout the assessed storage time. These results demonstrate the
      potential of CHI from C. elegans to control post-harvest pathogenic fungi in
      fruits, in particular, B. cinerea and P. expansum in table grapes.

PMID- 24321604
TI  - Anti-TNF-alpha therapy in the management of severe neurosarcoidosis: a report of
      five cases from a single centre and literature review.
AB  - Neurologic manifestations are found in 5-15 % of patients with sarcoidosis. This
      granulomatous disease may affect any part of the peripheral or the central
      nervous system, being potentially severe and difficult to treat. Corticosteroids
      are the cornerstone of therapy in sarcoidosis. However, some patients become
      resistant or experience side effects to corticosteroids. In these patients,
      second line therapies including immunosuppressive drugs such as methotrexate,
      azathioprine, mycophenolate, cyclophosphamide and leflunomide have been used.
      Anti-TNF-alpha drugs have been proposed as a therapeutic option for those who are
      refractory to immunosuppressive drugs or initially in cases of severe
      sarcoidosis. We report on 5 patients with neurosarcoidosis treated with anti-TNF
      alpha drugs in our center. A literature review of patients with neurosarcoidosis
      treated with anti-TNF-alpha drugs was conducted. In our series successful
      response to anti-TNF-alpha therapy was achieved. However, the high frequency of
      relapses following anti-TNF-alpha discontinuation makes necessary a close follow
      up of these patients when the biologic agent is stopped. 

PMID- 24321605
TI  - Thermal steam explosion pretreatment to enhance anaerobic biodegradability of the
      solid fraction of pig manure.
AB  - The assessment of the biodegradability of thermal steam-exploded pig manure was
      performed compared to untreated samples. The pre-treatment was performed under
      different combinations of temperature and time, ranging 150-180  degrees C and 5
      60 min, and used as substrate in a series of batch biochemical methane potential
      (BMP) tests. Results were analyzed in terms of methane yield, kinetic parameters
      and severity factor. In all the pre-treatment conditions, methane yield and
      degradation rates increased when compared to untreated pig slurry. An ANOVA study
      determined that temperature was the main factor, and the optimum combination of
      temperature-time of pretreatment was 170  degrees C -30 min, doubling methane
      production from 159 to 329 mL CH4/gVSfed. These operation conditions correspond
      to a severity factor of 3.54, which was considered an upper limit for the
      pretreatment due to the possible formation of inhibitory compounds, hindering the
      process if this limit is exceeded.

PMID- 24321606
TI  - An investigation of ultrasound effect on microalgal cell integrity and lipid
      extraction efficiency.
AB  - In this study, different ultrasound power intensities (0.1-0.5 W mL(-1)) were
      applied at a frequency of 30 kHz and for durations of 5-60 min to mixed
      microalgal cultures, one cultivated in BG11 medium, and the other in secondary
      effluent wastewater. The ultrasonic effect on cell disruption was revealed by
      increased concentrations of protein and carbohydrate released into the solution,
      and a decreased concentration of total suspended solids in cell suspension. The
      highest intercellular material release was achieved at an ultrasonic energy
      intensity of 0.4 kWh L(-1), while the effect of ultrasound on cell disruption was
      reduced at higher energy intensities. Additionally, the ultrasonic effect on
      lipid extraction efficiency was studied in the presence of two different
      solvents, n-hexane and chloroform/methanol mixture. The application of ultrasound
      at 0.4 kWh L(-1), provided 1.5-2.0-fold increase in lipid extraction yields in
      the presence of the solvents.

PMID- 24321607
TI  - Improvement of the fermentability of oxalic acid hydrolysates by detoxification
      using electrodialysis and adsorption.
AB  - A two-step detoxification process consisting of electrodialysis and adsorption
      was performed to improve the fermentability of oxalic acid hydrolysates. The
      constituents of the hydrolysate differed significantly between mixed hardwood and
      softwood. Acetic acid and furfural concentrations were high in the mixed
      hardwood, whereas 5-hydroxymethylfurfural (HMF) concentration was relatively low
      compared with that of the mixed softwood. The removal efficiency of acetic acid
      reached 100% by electrodialysis (ED) process in both hydrolysates, while those of
      furfural and HMF showed very low, due to non-ionizable properties. Most of the
      remaining inhibitors were removed by XAD-4 resin. In the mixed hardwood
      hydrolysate without removal of the inhibitors, ethanol fermentation was not
      completed. Meanwhile, both ED-treated hydrolysates successfully produced ethanol
      with 0.08 and 0.15 g/Lh ethanol productivity, respectively. The maximum ethanol
      productivity was attained after fermentation with 0.27 and 0.35 g/Lh of
      detoxified hydrolysates, which were treated by ED, followed by XAD-4 resin.

PMID- 24321608
TI  - Organosolv pretreatment of rice straw for efficient acetone, butanol, and ethanol
      production.
AB  - Acetone-butanol-ethanol (ABE) was produced from rice straw using a process
      containing ethanol organosolv pretreatment, enzymatic hydrolysis, and
      fermentation by Clostridium acetobutylicum bacterium. Pretreatment of the straw
      with 75% (v/v) aqueous ethanol containing 1% w/w sulfuric acid at 150  degrees C
      for 60 min resulted in the highest total sugar concentration of 31 g/L in the
      enzymatic hydrolysis. However, the highest ABE concentration and productivity
      (10.5 g/L and 0.20 g/Lh, respectively) were obtained from the straw pretreated at
      180  degrees C for 30 min. Enzymatic hydrolysis of the straw pretreated at 180 
      degrees C for 30 min with 5% solid loading resulted in glucose yield of 46.2%,
      which was then fermented to 80.3 g butanol, 21.1 g acetone, and 22.5 g ethanol,
      the highest overall yield of ABE production. Thus, the organosolv pretreatment
      can be applied for efficient production of the solvents from rice straw.

PMID- 24321609
TI  - Packed bed column studies on lead(II) removal from industrial wastewater by
      modified Agaricus bisporus.
AB  - Agaricus bisporus showed best performance in removing Pb(II) with a biosorption
      capacity of 86.4 mg g(-1) after modification with NaOH. In this work, the removal
      of Pb(II) from wastewater has been conducted in column mode. The metal removal
      was dependent on the flow rate, initial metal concentration, and bed height. The
      experimental data obtained from the biosorption process was successfully
      correlated with the Bohart-Adams, Thomas, and Yoon-Nelson models. Five
      biosorption-desorption cycles yielded 95.34%, 92.27%, 90.13%, 86.75%, and 81.52%
      regeneration, respectively. Pb(II) could be effectively removed from industrial
      wastewater; some metal ions and organics were also removed concomitantly, and the
      obtained effluent had characteristics of better quality. The results confirmed
      that modified A. bisporus could be applied for the removal of heavy metals from
      industrial wastewater in a continuous column process.

PMID- 24321610
TI  - Evaluating predictive modeling algorithms to assess patient eligibility for
      clinical trials from routine data.
AB  - BACKGROUND: The necessity to translate eligibility criteria from free text into
      decision rules that are compatible with data from the electronic health record
      (EHR) constitutes the main challenge when developing and deploying clinical trial
      recruitment support systems. Recruitment decisions based on case-based reasoning,
      i.e. using past cases rather than explicit rules, could dispense with the need
      for translating eligibility criteria and could also be implemented largely
      independently from the terminology of the EHR's database. We evaluated the
      feasibility of predictive modeling to assess the eligibility of patients for
      clinical trials and report on a prototype's performance for different system
      configurations. METHODS: The prototype worked by using existing basic patient
      data of manually assessed eligible and ineligible patients to induce prediction
      models. Performance was measured retrospectively for three clinical trials by
      plotting receiver operating characteristic curves and comparing the area under
      the curve (ROC-AUC) for different prediction algorithms, different sizes of the
      learning set and different numbers and aggregation levels of the patient
      attributes. RESULTS: Random forests were generally among the best performing
      models with a maximum ROC-AUC of 0.81 (CI: 0.72-0.88) for trial A, 0.96 (CI: 0.95
      0.97) for trial B and 0.99 (CI: 0.98-0.99) for trial C. The full potential of
      this algorithm was reached after learning from approximately 200 manually
      screened patients (eligible and ineligible). Neither block- nor category-level
      aggregation of diagnosis and procedure codes influenced the algorithms'
      performance substantially. CONCLUSIONS: Our results indicate that predictive
      modeling is a feasible approach to support patient recruitment into clinical
      trials. Its major advantages over the commonly applied rule-based systems are its
      independency from the concrete representation of eligibility criteria and EHR
      data and its potential for automation.

PMID- 24321611
TI  - Towards a simple objective framework for the investigation and treatment of
      cancer cachexia: the Glasgow Prognostic Score.
AB  - Progress in the treatment of progressive involuntary weight loss in patients with
      cancer (cancer cachexia) remains dismally slow. Cancer cachexia and its
      associated clinical symptoms, including weight loss, altered body composition,
      poor functional status, poor food intake, and poorer quality of life, have long
      been recognised as indicators of poorer prognosis in the patient with cancer. In
      order to make some progress a starting point is to have general agreement on what
      constitutes cancer cachexia. In recent years a plethora of different definitions
      and consensus statements have been proposed as a framework for investigation and
      treatment of this debilitating and terminal condition. However, there are
      significant differences in the criteria used in these and all include poorly
      defined or subjective criteria and their prognostic value has not been
      established. The aim of the present review was to examine the hypothesis that a
      systemic inflammatory response accounts for most of the effect of cancer cachexia
      and its associated clinical symptoms on poor outcome in patients with cancer.
      Furthermore, to put forward the case for the Glasgow Prognostic Score to act a
      simple objective framework for the investigation and treatment of cancer
      cachexia. 

PMID- 24321612
TI  - Uterine leiomyomata and cesarean birth risk: a prospective cohort with
      standardized imaging.
AB  - PURPOSE: To determine if women with leiomyomata detected using uniform ultrasound
      methods are at increased risk of cesarean birth, without regard to indication.
      METHODS: Women were enrolled in Right from the Start (2000-2010), a prospective
      pregnancy cohort. Leiomyomata were counted, categorized, and measured during
      first trimester ultrasounds. Women provided information about demographics and
      reproductive history during first trimester interviews. Route of delivery was
      extracted from medical records or vital records, if the former were unavailable.
      Generalized estimating equations were used to calculate risk ratios (RR) and 95%
      confidence intervals (CIs) for the risk of cesarean birth by leiomyoma presence
      and characteristics. RESULTS: Among 2635 women, the prevalences of leiomyomata
      and cesarean birth were 11.2% and 29.8%, respectively. Women with leiomyomata,
      compared with those without, had a 27% increase in cesarean risk (RR, 1.27; CI,
      1.17-1.37). The association was weaker following adjustment for maternal body
      mass index and age (adjusted risk ratio [ARR], 1.11; CI, 1.02-1.20). The adjusted
      risk was elevated for women with a single leiomyoma 3 cm or more in diameter
      (ARR, 1.22; CI, 1.14-1.32) and women with the largest total leiomyoma volumes
      (ARR, 1.59; CI, 1.44-1.76). CONCLUSIONS: Women with leiomyomata were at increased
      risk for cesarean birth particularly, those with larger tumor volumes.

PMID- 24321613
TI  - Behavioral effects of different enriched environments in mice treated with the
      cholinergic agonist PNU-282987.
AB  - Environmental enrichment is an experimental model in which rodents are housed in
      complex environments that favor lower levels of anxiety-like behavior. PNU-282987
      (PNU) is a alpha7 nicotinic acetylcholine receptor agonist with beneficial
      effects on learning though its effects on anxiety are unclear. Our main aim was
      to carry out a study of its effects in NMRI (n=96) mice reared in different
      environments: environmental enrichment (EE), MarlauTM cages (MC) and standard
      environment (SE). After a 4-month period, mice received acute treatment of PNU
      (2.5, 5 and 10mg/kg) and were evaluated in the elevated plus-maze (EPM) and hole
      board (HB). In the EPM, both EE and MC reared mice showed an increase in
      percentage of entries into open arms while those from EE group differed from SE
      in time spent on open arms. Mice treated with 2.5 and 10 mg/kg of PNU devoted
      less time to rearing into open arms. In the HB task, MC mice displayed higher
      exploratory activity reflected in more head-dips (HD) during the first minute
      than EE and SE, whereas EE displayed low exploration levels reflected in total HD
      (5 min). Further research is needed in order to clarify the behavioral effects of
      this nicotinic agonist in interaction with different environmental conditions.
      This article is part of a Special Issue entitled: insert SI title.

PMID- 24321614
TI  - Compressed classification learning with Markov chain samples.
AB  - In this article, we address the problem of compressed classification learning. A
      generalization bound of the support vector machines (SVMs) compressed
      classification algorithm with uniformly ergodic Markov chain samples is
      established. This bound indicates that the accuracy of the SVM classifier in the
      compressed domain is close to that of the best classifier in the data domain. In
      a sense, the fact that the compressed learning can avoid the curse of
      dimensionality in the learning process is shown. In addition, we show that
      compressed classification learning reduces the learning time at the price of
      decreasing the classification accuracy, but the decrement can be controlled. The
      numerical experiments further verify the results claimed in this article. 

PMID- 24321615
TI  - Finite time convergent learning law for continuous neural networks.
AB  - This paper addresses the design of a discontinuous finite time convergent
      learning law for neural networks with continuous dynamics. The neural network was
      used here to obtain a non-parametric model for uncertain systems described by a
      set of ordinary differential equations. The source of uncertainties was the
      presence of some external perturbations and poor knowledge of the nonlinear
      function describing the system dynamics. A new adaptive algorithm based on
      discontinuous algorithms was used to adjust the weights of the neural network.
      The adaptive algorithm was derived by means of a non-standard Lyapunov function
      that is lower semi-continuous and differentiable in almost the whole space. A
      compensator term was included in the identifier to reject some specific
      perturbations using a nonlinear robust algorithm. Two numerical examples
      demonstrated the improvements achieved by the learning algorithm introduced in
      this paper compared to classical schemes with continuous learning methods. The
      first one dealt with a benchmark problem used in the paper to explain how the
      discontinuous learning law works. The second one used the methane production
      model to show the benefits in engineering applications of the learning law
      proposed in this paper. 

PMID- 24321616
TI  - Cerebellar dentate nuclei lesions alter prefrontal cortex dendritic spine
      morphology.
AB  - Anatomical tracing studies in primates have revealed neural tracts from the
      cerebellar dentate nuclei to prefrontal cortex, implicating a cerebellar role in
      nonmotor processes. Experiments in rats examining the functional role of this
      cerebellothalamocortical pathway have demonstrated the development of
      visuospatial and motivational deficits following lesions of the dentate nuclei,
      in the absence of motor impairment. These behavioral deficits possibly occur due
      to structural modifications of the cerebral cortex secondary to loss of
      cerebellar input. The current study characterized morphological alterations in
      prefrontal cortex important for visuospatial and motivational processes following
      bilateral cerebellar dentate nuclei lesions. Rats received either bilateral
      electrolytic cerebellar dentate nuclei lesions or sham surgery followed by a 30
      day recovery. Randomly selected Golgi-impregnated neurons in prefrontal cortex
      were examined for analysis. Measures of branch length and spine density revealed
      no differences between lesioned and sham rats in either apical or basilar arbors;
      however, the proportion of immature to mature spines significantly decreased in
      lesioned rats as compared to sham controls, with reductions of 33% in the basilar
      arbor and 28% in the apical arbor. Although expected pruning of branches and
      spines did not occur, the results are consistent with the hypothesis that
      cerebellar lesions influence prefrontal morphology and support the possibility
      that functional deficits following cerebellar dentate nuclei lesions are related
      to prefrontal morphological alteration. 

PMID- 24321617
TI  - Combined treatment with acupuncture reduces effective dose and alleviates adverse
      effect of L-dopa by normalizing Parkinson's disease-induced neurochemical
      imbalance.
AB  - This study first showed the behavioural benefits of novel combination therapy of
      L-dopa with acupuncture on Parkinson's disease, and its underlying mechanisms
      within basal ganglia. The previous study reported that acupuncture may improve
      the motor function of a Parkinson's disease (PD) mouse model by increasing the
      dopamine efflux and turnover ratio of dopamine. Hence, we hypothesised that
      combining L-dopa with acupuncture would have a behavioural benefit for those with
      PD. We performed unilateral injections of 6-OHDA into the striatum of C57Bl/6
      mice to model hemi-Parkinsonian attributes. To test motor function and dyskinetic
      anomalies, we examined cylinder behaviour and abnormal involuntary movement
      (AIM), respectively. We found that (1) a 50% reduced dose of L-dopa (7.5 mg/kg)
      combined with acupuncture showed an improvement in motor function that was
      comparable to mice given the standard dose of L-dopa treatment (15 mg/kg) only,
      and that (2) the combination treatment (L-dopa +acupuncture) was significantly
      superior in reducing AIM scores when equivalent doses of L-dopa were used. The
      combination treatment also significantly reduces the abnormal increase of GABA
      contents in the substantia nigra compared to the standard L-dopa treatment.
      Furthermore, abnormal expression of FosB, the immediate early gene of L-dopa
      induced dyskinesia (LID), was mitigated in the striatum by the combination
      treatment. All of these results indicate that acupuncture enhances the benefits
      of L-dopa on motor function with reduced dose of L-dopa and alleviating LID by
      normalising neurochemical imbalance within the basal ganglia.

PMID- 24321618
TI  - Neuroanatomic pathway associated with attentional deficits after stroke.
AB  - We used magnetic resonance imaging (MRI) and the statistical parametric mapping
      (SPM) image analysis technique to localize lesions in post-stroke patients with
      attention deficits. SPM can be used to combine image data from multiple
      participants and correlate these images with other data sets. Magnetic resonance
      imaging acquisitions were obtained from 115 post-stroke patients, who were
      systemically assessed for attention deficits using a standardized test (the
      Clinical Assessment for Attention; CAT) that probes various domains of attention.
      We created an SPM that displayed an association between lesion location and
      attention deficit severity. The overlay plots were localized to the right
      hemisphere during a visual cancellation test, and were localized to the left
      hemisphere during other attention tests. Cortical lesion varied across specific
      test domain, whereas lesions from the thalamus to the basal ganglia on the
      dominant side were associated with performance across all attention
      tests/domains. Our findings are suggestive of a large-scale multimodal
      attentional network associated with the thalamus/basal ganglia. 

PMID- 24321619
TI  - Local injection versus surgery in carpal tunnel syndrome: neurophysiologic
      outcomes of a randomized clinical trial.
AB  - OBJECTIVE: The aim of our study was to characterize the neurophysiologic outcomes
      in a randomized clinical trial comparing local corticosteroid injection and
      decompressive surgery in idiopathic carpal tunnel syndrome. METHODS: Clinical and
      neurophysiologic assessments were done at baseline and 12 months after treatment.
      Four parameters were evaluated in the nerve conduction study (NCS): distal motor
      latency, motor amplitude, sensory conduction velocity and sensory amplitude.
      Statistic signification was established by the Student's t test, independent and
      paired samples, and Mann-Whitney test. Repeated measures analysis of variance was
      used by the three domains of symptoms. Correlations between the changes showed in
      clinical parameters and those evidenced by electromyography were calculated by
      the Pearson's test. RESULTS: Both groups of therapy were comparable at baseline.
      In 95 wrists, a second NCS was done 12 months post-treatment. Although clinical
      outcome improved in a similar way in both groups, we found statistically
      significant improvement in three (distal motor latency, sensory conduction
      velocity and sensory amplitude) of four neurophysiologic parameters only in the
      surgery group, when compared to baseline values. CONCLUSIONS: Although local
      corticosteroid injection and decompressive surgery are clinically effective in
      reducing symptoms of carpal tunnel syndrome, only surgery results in an
      improvement of the neurophysiologic parameters, at 12-months follow-up.
      SIGNIFICANCE: Only decompressive surgery allows resolution of neurophysiologic
      changes. The symptoms of the syndrome are resolved with corticosteroid
      injections.

PMID- 24321620
TI  - Impaired neural conduction in the auditory brainstem of high-risk very preterm
      infants.
AB  - OBJECTIVE: To test the hypothesis that neural conduction in the auditory
      brainstem is impaired in high-risk very preterm infants. METHODS: Eighty-two very
      preterm infants (gestation 28-32 weeks) with various perinatal problems or
      complications were studied at term using maximum length sequence (MLS) brainstem
      auditory evoked response (BAER) with click rates 91-910/s. The data were compared
      with those in 31 age-matched low-risk very preterm infants and 44 normal
      gestation (term) infants. RESULTS: High-risk very preterm infants showed a
      general increase in MLS BAER wave latencies and interpeak intervals. Wave V
      latency, and III-V and I-V intervals in high-risk very preterm infants were
      significantly longer than in normal term infants at all click rates, particularly
      higher rates. I-III interval was significantly longer, and III-V/I-III interval
      ratio was significantly greater at higher rates. These latency and intervals in
      high-risk very preterm infants were also longer, though relatively less
      significantly, than in low-risk very preterm infants. Click rate-related changes
      in major MLS BAER variables in high-risk infants were more significant than in
      the two groups of controls. CONCLUSIONS: There were major abnormalities in MLS
      BAER variables that mainly reflect central neural conduction in high-risk very
      preterm infants. The abnormalities were relatively less significant when compared
      with low-risk very preterm infants than with normal term infants. SIGNIFICANCE:
      Neural conduction in the auditory brainstem, mainly the more central regions, is
      impaired in high-risk very preterm infants. The impairment is largely attributed
      to the associated perinatal problems, and partially related to very preterm
      birth.

PMID- 24321621
TI  - Experimental Chagas disease. Innate immune response in Balb/c mice previously
      vaccinated with Trypanosoma rangeli. I. The macrophage shows immunological
      memory: Reality or fiction?
AB  - Chagas' disease, caused by Trypanosoma cruzi, is a major vector borne health
      problem in Latin America and an emerging or re-emerging infectious disease in
      several countries. Immune response to T. cruzi infection is highly complex and
      involves many components, both regulators and effectors. Although different
      parasites have been shown to activate different mechanisms of innate immunity, T.
      cruzi is often able to survive and replicate in its host because they are well
      adapted to resisting host defences. An experimental model for vaccinating mice
      with Trypanosoma rangeli, a parasite closely related to T. cruzi, but
      nonpathogenic to humans, has been designed in our laboratory, showing protection
      against challenge with T. cruzi infection. The aim of this work was to analyze
      some mechanisms of the early innate immune response in T. rangeli vaccinated mice
      challenged with T. cruzi. For this purpose, some interactions were studied
      between T. cruzi and peritoneal macrophages of mice vaccinated with T. rangeli,
      infected or not with T. cruzi and the levels of some molecules or soluble
      mediators which could modify these interactions. The results in vaccinated
      animals showed a strong innate immune response, where the adherent cells of the
      vaccinated mice revealed important phagocytic activity, and some soluble mediator
      (Respiratory Burst: significantly increase, p <= 0.03; NO: the levels of
      vaccinated animals were lower than those of the control group; Arginasa:
      significantly increase, p <= 0.04). The results showed an important role in the
      early elimination of the parasites and their close relation with the absence of
      histological lesions that these animals present with regard to the only infected
      mice. This behaviour reveals that the macrophages act with some type of memory,
      recognizing the antigens to which they have previously been exposed, in mice were
      vaccinated with T. rangeli, which shares epitopes with T. cruzi.

PMID- 24321622
TI  - Oral pretreatment with recombinant human lactoferrin limits trauma-hemorrhagic
      shock-induced gut injury and the biological activity of mesenteric lymph.
AB  - BACKGROUND: Lactoferrin (LF) is a pleiotropic glycoprotein that is found in
      bodily secretions and is postulated to enhance the gastrointestinal barrier and
      promote mucosal immunity. Thus, the ability of talactoferrin, an oral recombinant
      form of human LF, to limit gut injury and the production of biologically active
      gut-derived products was tested using a rat model of trauma-hemorrhagic shock
      (T/HS). METHODS: Male rats were orally dosed with vehicle or talactoferrin (1000
      mg/kg, every day) for 5 d before being subjected to T/HS or trauma-sham shock
      (T/SS). Subsequently, rats were subjected to a laparotomy (trauma) and
      hemorrhagic shock (mean arterial pressure, 30-35 mm Hg * 90 min) or to T/SS,
      followed by resuscitation with their shed blood. Before inducing shock, the
      mesenteric lymphatic duct was catheterized for collection of mesenteric lymph.
      Four hours after the end of the shock or sham-shock period, rats were sacrificed,
      a segment of the distal ileum was collected for morphologic analysis, and lymph
      samples were processed and frozen. Subsequently, lymph samples were tested in
      several pharmacodynamic assays, including endothelial cell permeability,
      neutrophil respiratory burst activity, and red blood cell (RBC) deformability.
      Total white blood cell counts in lymph samples were also quantified. RESULTS:
      Pretreatment with talactoferrin reduced the incidence of T/HS-induced morphologic
      injury of ileum to T/SS levels. Post-T/HS lymph from vehicle-treated rats
      increased endothelial monolayer permeability and neutrophil priming for an
      augmented respiratory burst, and induced loss of RBC deformability, compared with
      T/SS groups. Talactoferrin pretreatment significantly reduced the biological
      activity of T/HS lymph on respiratory burst activity and RBC deformability, but
      had no effect on the lymph cell count or endothelial cell permeability.
      CONCLUSIONS: These results provide a proof of principle that prophylactic dosing
      of oral talactoferrin can potentially protect the gut in a T/HS model and limit
      the production of biologically active factors in rat gastrointestinal tissue
      subjected to ischemia-reperfusion-type injuries.

PMID- 24321624
TI  - Water source and diarrhoeal disease risk in children under 5 years old in
      Cambodia: a prospective diary based study.
AB  - BACKGROUND: Despite claims that the Millennium Development Goals (MDG) targets on
      access to safe drinking water have been met, many 100 s of millions of people
      still have no access. The challenge remains how to provide these people and
      especially young children with safe drinking water. METHOD: We report a
      longitudinal study designed to assess the effectiveness of an intervention based
      on provided treated drinking water in containers on self-reported diarrhoea in
      children. The intervention was "1001 fontaines pour demain" (1001 F) is a non
      governmental not for profit organization (created in 2004 and based in Caluire,
      France) that helps local entrepreneurs treat package, and sell safe drinking
      water. Cases and controls were chosen at village and household level by
      propensity score matching Participants were visited twice a month over six months
      and asked to complete a diarrhoea health diary. RESULTS: In total 4275 follow-up
      visits were completed on 376 participants from 309 homes. Diarrhoea was reported
      in 20.4% of children on each visit, equating to an incidence rate estimate of
      5.32 episodes per child per year (95% confidence interval = 4.97 to 5.69).
      Compared to those drinking 1001 F water, children drinking surface water were 33%
      (95% CI -1 to 17%), those drinking protected ground water were 62% (95% CI 19 to
      120%) and those drinking other bottled water 57% (95% CI 15 to 114%) more likely
      to report diarrhoea. Children drinking harvested rainwater had similar rates of
      diarrhoea to Children drinking 1001 F water. CONCLUSION: Our study suggests that
      1001 F water provides a safer alternative to groundwater or surface water.
      Furthermore, our study raises serious concerns about the validity of assuming
      protected groundwater to be safe water for the purposes of assessing the MDG
      targets. By contrast our study provides addition evidence of the relative safety
      of rainwater harvesting.

PMID- 24321623
TI  - Preverbal infants identify emotional reactions that are incongruent with goal
      outcomes.
AB  - Identifying the goal of another agent's action allows an observer to make
      inferences not only about the outcomes the agent will pursue in the future and
      the means to be deployed in a given context, but also about the emotional
      consequences of goal-related outcomes. While numerous studies have characterized
      the former abilities in infancy, expectations about emotions have gone relatively
      unexplored. Using a violation of expectation paradigm, we present infants with an
      agent who attains or fails to attain a demonstrated goal, and reacts with
      positive or negative affect. Across several studies, we find that infants'
      attention to a given emotional display differs depending on whether that reaction
      is congruent with the preceding goal outcome. Specifically, infants look longer
      at a negative emotional display when it follows a completed goal compared to when
      it follows a failed goal. The present results suggest that infants' goal
      representations support expectations not only about future actions but also about
      emotional reactions, and that infants in the first year of life can relate
      different emotional reactions to conditions that elicit them. 

PMID- 24321625
TI  - Unraveling the characteristics of microRNA regulation in the developmental and
      aging process of the human brain.
AB  - BACKGROUND: Structure and function of the human brain are subjected to dramatic
      changes during its development and aging. Studies have demonstrated that
      microRNAs (miRNAs) play an important role in the regulation of brain development
      and have a significant impact on brain aging and neurodegeneration. However, the
      underlining molecular mechanisms are not well understood. In general, development
      and aging are conventionally studied separately, which may not completely address
      the physiological mechanism over the entire lifespan. Thus, we study the
      regulatory effect between miRNAs and mRNAs in the developmental and aging process
      of the human brain by integrating miRNA and mRNA expression profiles throughout
      the lifetime. METHODS: In this study, we integrated miRNA and mRNA expression
      profiles in the human brain across lifespan from the network perspective. First,
      we chose the age-related miRNAs by polynomial regression models. Second, we
      constructed the bipartite miRNA-mRNA regulatory network by pair-wise correlation
      coefficient analysis between miRNA and mRNA expression profiles. At last, we
      constructed the miRNA-miRNA synergistic network from the miRNA-mRNA network,
      considering not only the enrichment of target genes but also GO function
      enrichment of co-regulated target genes. RESULTS: We found that the average
      degree of age-related miRNAs was significantly higher than that of non age
      related miRNAs in the miRNA-mRNA regulatory network. The topological features
      between age-related and non age-related miRNAs were significantly different, and
      34 reliable age-related miRNA synergistic modules were identified using Cfinder
      in the miRNA-miRNA synergistic network. The synergistic regulations of module
      genes were verified by reviewing miRNA target databases and previous studies.
      CONCLUSIONS: Age-related miRNAs play a more important role than non age-related
      mrRNAs in the developmental and aging process of the human brain. The age-related
      miRNAs have synergism, which tend to work together as small modules. These
      results may provide a new insight into the regulation of miRNAs in the
      developmental and aging process of the human brain.

PMID- 24321626
TI  - Exploring why quality circles work in primary health care: a realist review
      protocol.
AB  - BACKGROUND: Quality circles (QCs) are commonly used in primary health care in
      Europe to consider and improve standard practice over time. They represent a
      complex social intervention that occurs within the fast-changing system of
      primary health care. Numerous controlled trials, reviews, and studies have shown
      small but unpredictable positive effect sizes on behavior change. Although QCs
      seem to be effective, stakeholders have difficulty understanding how the results
      are achieved and in generalizing the results with confidence. They also lack
      understanding of the active components of QCs which result in changes in the
      behavior of health care professionals. This protocol for a realist synthesis will
      examine how configurations of components and the contextual features of QCs
      influence their performance. METHODS/DESIGN: Stakeholder interviews and a scoping
      search revealed the processes of QCs and helped to describe their core components
      and underlying theories. After clarifying their historical and geographical
      distribution, a purposive and systematic search was developed to identify
      relevant papers to answer the research questions, which are: understanding why,
      how, and when QCs work, over what time frame, and in what circumstances. After
      selecting and abstracting appropriate data, configurations of contexts and
      mechanisms which influence the outcome of QCs within each study will be
      identified. Studies will be grouped by similar propositional statements in order
      to identify patterns and validation from stakeholders sought. Finally, theories
      will be explored in order to explain these patterns and to help stakeholders
      maintain and improve QC performance. DISCUSSION: Analyzing context-mechanism
      outcome (CMO) patterns will reveal how QCs work and how contextual factors
      interact to influence their outcome. The aim is to investigate unique
      configurations that enable them to improve the performance of health care
      professionals. Using a standardized reporting system, this realist review will
      allow the research questions to be answered to the satisfaction of key
      stakeholders and enable on-going critical examination and dissemination of the
      findings. STUDY REGISTRATION: PROSPERO registration number: CRD42013004826.

PMID- 24321627
TI  - Multi-well imaging of development and behavior in Caenorhabditis elegans.
AB  - BACKGROUND: The nematode Caenorhabditis elegans is widely used as a model for
      understanding the neuronal and genetic bases of behavior. Recent studies have
      required longitudinal assessment of individual animal's behavior over extended
      periods. NEW METHOD: Here we present a technique for automated monitoring of
      multiple worms for several days. Our method uses an array of plano-concave glass
      wells containing standard agar media. The concave well geometry allows worms to
      be imaged even at the edge of the agar surface and prevents them from burrowing
      under the agar. We transfer one worm or embryo into each well, and perform
      imaging of the array of wells using a single camera. Machine vision software is
      used to quantify size, activity, and/or fluorescence of each worm over time.
      RESULTS: We demonstrate the utility of our method in two applications: (1)
      quantifying behavioral quiescence and developmental rate in wild-type and mutant
      animals, and (2) characterizing differences in mating behavior between two C.
      elegans strains. COMPARISON WITH EXISTING METHOD(S): Current techniques for
      tracking behavior in identified worms are generally restricted to imaging either
      single animals or have not been shown to work with arbitrary developmental
      stages; many are also technically complex. Our system works with up to 24 animals
      of any stages and is technically simple. CONCLUSIONS: Our multi-well imaging
      method is a powerful tool for quantification of long-term behavioral phenotypes
      in C. elegans.

PMID- 24321629
TI  - Study on lockout procedures for the safety of workers intervening on equipment in
      the municipal sector in Quebec.
AB  - In Quebec, workers intervening in hazardous zones of machines, equipment and
      processes during maintenance, repairs and unjamming activities have to apply
      lockout procedures. Lockout procedures involve shutting down the equipment,
      isolating it, applying individual locks, releasing residual energies and
      verifying the absence of energies. Lockout has mostly been linked to industrial
      sectors. However, the municipal sector also faces challenges when it comes to
      controlling hazardous energies. The objectives of this research are to study
      serious accidents linked to our subject, study the application of lockout in
      different municipalities in Quebec, identify the specificities for the municipal
      sector and propose some means to support the application of lockout. We will show
      that lockout procedures are required in different locations in municipalities and
      that they are currently being implemented in the municipal sector in Quebec.
      Moreover, we propose a model which aims at facilitating the implementation of
      lockout procedures in the municipal sector. 

PMID- 24321628
TI  - Hospital admissions in Alicante (Spain): a comparative analysis of foreign
      citizens from high-income countries, immigrants from low-income countries, and
      Spanish citizens.
AB  - BACKGROUND: Over the last decade, the number of foreign citizens (FCs) in Spain
      has increased. There is no doubt that their health has become a relevant subject
      from the point of view of public healthcare. Our study aimed to describe hospital
      admission rates, diagnoses at hospital discharge, and mortality during hospital
      admissions in FCs from high-income countries (FCHICs), FCs from low-income
      countries (FCLICs), and autochthonous citizens (ACs). METHODS: A cross-sectional
      study was performed at two public hospitals in the city of Alicante (Spain) and
      its surrounding area. Utilization rates were estimated. Multivariate analysis
      adjusting for age and sex was performed on hospital admission rates, diagnoses at
      hospital discharge, service of admission, and mortality during hospital admission
      in FCHICs and FCLICs compared with ACs (adjusted odds ratio [AOR] with 95%
      confidence intervals [CI]). RESULTS: 42,839 patients >=15 years were discharged
      from the hospitals. The utilization rate was lower in FCs than ACs, whose crude
      rate ratio was 0.676 (95% CI: 0.656-0.696). FCHICs had more risk of being
      diagnosed at discharge in the categories of the circulatory system (AOR: 1.55;
      95% CI: 1.35-1.77), neoplasms (AOR: 1.21; 95% CI: 1.03-1.42), and injury and
      poisoning (AOR: 1.33; 95% CI: 1.11-1.58). FCLICs had more risk of being diagnosed
      in the categories of pregnancy, childbirth & puerperium (AOR: 1.33; 95% CI: 1.29
      1.59), and injury and poisoning (AOR: 1.19; 95% CI: 1.03-1.36), and less risk in
      the mental disorder category (AOR: 0.32; 95% CI: 0.22-0.45). The length of
      hospitalization (in days) was lower in FCLICs (median: 3; IQR: 2-6) than both ACs
      (median: 4; IQR: 2-8) and FCHICs (median: 4; IQR: 2-8) (p < 0.001). The mortality
      rates on admission of ACs, FCHICs, and FCLICs were 4.2%, 3.3%, and 1.3%,
      respectively, but after adjusting for age and sex, the mortality rate risks were
      similar in FCHICs and FCLICs. CONCLUSION: First, FCs utilized hospitalization
      less when compared with ACs. Second, the hospitalization profile for FCHICs was
      similar to ACs, with more problems in the circulatory system, and the
      hospitalization profile for FCLICs was different compared with ACs, with more
      admissions for pregnancy, childbirth & puerperium.

PMID- 24321630
TI  - Effects of physical and personal risk factors on sick leave due to
      musculoskeletal disorders.
AB  - The purpose of this study was to investigate the effects of physical and personal
      risk factors on sick leave due to musculoskeletal disorders in an Iranian car
      company. In this cross-sectional study, 234 workers participated and all of them
      had sick leave due to musculoskeletal disorders in the past year. A physical risk
      factor checklist and personal information questionnaire were used as data
      gathering tools. There was no significant relationship between physical risk
      factors and sick leave (p > .05). Cigarette smoking (p = .045), body mass index
      >30 (p = .046) and age (p = .044) showed a significant relationship with sick
      leave. Workers with lumbar deviation of 20 degrees -60 degrees  (OR 1.10) and >60
      degrees  (OR 1.11) were at greater risk. The ratios for workers with repetitive
      work (OR 1.30) and workers with force exertion (OR 1.36) were greater than for
      other workers. Taking preventive actions to improve the ergonomic working
      conditions of assembly workers and their lifestyle seems crucial. 

PMID- 24321631
TI  - Safety climate and prediction of ergonomic behavior.
AB  - One of the most important ways to prevent accidents is to consider safety climate
      or culture. Moreover, some studies suggest that behavior contributes to 86%-96%
      of all injuries. This cross-sectional study took place in an Iranian
      petrochemical company in 2010. Vinodkumar and Bhasi's safety climate
      questionnaire and an ergonomic behavior sampling checklist were the data
      collection tools. Cronbach's alpha for questionnaire reliability was .928. With
      reference to the results of a pilot study, a sample of 1755 was determined for
      behavior sampling. We used principal component analysis (PCA) to derive the
      coefficient of paths in the path model and the Anderson-Rabin method to calculate
      factor scores. The results showed that safety climate was an effective predictor
      of ergonomic behavior (p < .01). They also showed the importance of decreasing
      the number of workers with negative safety climate. Moreover, it is necessary to
      promote workers' ergonomic behaviors in the workplace. 

PMID- 24321632
TI  - Heuristic procedure for the assembly line balancing problem with postural load
      smoothness.
AB  - This paper presents a heuristic procedure for assigning assembly tasks to
      workstations where both productivity and ergonomics issues are considered
      concurrently. The procedure uses Kilbridge and Wester's algorithm to obtain an
      initial task-workstation assignment solution which minimizes the balance delay of
      an assembly line. A task reassignment algorithm was applied to improve the
      initial solution by exchanging assembly tasks, which smooth postural load among
      workers, between workstations. A composite index of variation was used to measure
      the effectiveness of the task-workstation assignment solution. On the basis of
      clothes assembling, it was found that the task-workstation assignment solution
      with a minimum composite index of variation can be obtained with relatively equal
      weights in balance delay and postural load. 

PMID- 24321633
TI  - A carpet-weaver's chair based on anthropometric data.
AB  - Ergonomic design of chairs has been well studied by ergonomists. Chair design
      based on anthropometric data analysis is recommended. Weavers in carpet-weaving
      workshops use chairs with backrests and armrests. An anthropometric survey was
      carried out among weavers in Tabriz, Iran, to design a flexible chair and to
      improve its comfort on the basis of design dimensions. This study focused on the
      design dimensions of a chair for weavers and its recommended dimensions. The
      developed chair needs to be tested for its effects on weavers' posture and
      comfort. 

PMID- 24321634
TI  - Respiratory impairment in cotton-ginning workers exposed to cotton dust.
AB  - Dust generated during the handling and processing of cotton causes ill health of
      ginning workers. The purpose of this study was to determine the prevalence of
      respiratory symptoms among cotton-ginning workers. This study involved 188
      workers of 10 cotton-ginning factories. Forced vital capacity (FVC), peak
      expiratory flow rate (PEFR), and forced expiratory volume in 1 s (FEV1) declined
      significantly with increasing duration of exposure (p < .001) of the cotton
      ginning workers. Results of a standard respirator medical evaluation
      questionnaire indicated that, depending on duration of exposure, 51%-71% of
      cotton-ginning workers suffered from chest tightness, 55%-62% experienced chest
      pain, while 33%-42% of the workers reported frequent cough. Blood tests of the
      workers showed higher values of erythrocyte sedimentation rate, eosinophils, and
      white blood cells when exposure was longer. Byssinosis symptoms were observed
      among the workers. We recommend regular periodical medical check-ups, compulsory
      use of personal protective equipment, and proper ventilation at the workplace. 

PMID- 24321635
TI  - Dental ergonomics to combat musculoskeletal disorders: a review.
AB  - Musculoskeletal disorders (MSDs) are significant workplace problems affecting
      occupational health, productivity and the careers of dental professionals. The
      prevalence of MSDs is on the rise for all types of dental workers. In spite of
      different patterns of work culture, there are parallel levels of symptoms in
      dentists across nations. Risk factors for MSDs are multifactorial. Symptoms
      appear very early in careers, with higher prevalence of MSDs even during
      educational training. Ergonomics improvements, health promotion and
      organizational interventions are necessary to reduce the risk. An
      interdisciplinary approach with progressive efforts should be taken to address
      MSDs in dental professionals. 

PMID- 24321636
TI  - Disparity of a seat cushion and its influence on postural control.
AB  - Properties of supporting surfaces of a seat have an influence on postural
      control. Centre of pressure (COP) displacement parameters reflect both the
      balance controlling process and movements of the centre of a mass of entire body.
      The subjects of the study were 9 healthy men. A seat cushion was examined with a
      2-force platform setup. Force exertion at a seat pan and feet and COP
      displacement at a seat pan were measured to analyse postural control. Analysis of
      variance determined the differences in postural control depending on a cushion
      type among the subjects. Significant differences in COP displacement parameters
      were in COP trajectory length, medio-lateral COP displacement and COP velocity.
      The results of the study showed that foam cushion ensures better postural
      control. 

PMID- 24321637
TI  - Postural stability of sitting women.
AB  - The study examined the utility of stabilometric dimensions and explored whether
      the changes in sitting postures were manifested in functional measures of
      postural control. Eleven women participated in the study, which used 11 chair
      sitting postures: arms on laps or arms right angled; armrest at a height of 17,
      20 and 23 cm; with or without backrest; slouch or straight back; legs right
      angled at knees or crossed legs. The backrest and armrest shifted 16.3% of body
      weight from a seat pan. The characteristics of stabilometric dimensions evaluated
      the influence of seat components and sitting behaviour on postural balance. The
      study attempted to evaluate stability and its application in human-seat interface
      design. 

PMID- 24321638
TI  - Electric versus hydraulic hospital beds: differences in use during basic nursing
      tasks.
AB  - Biomechanical, postural and ergonomic aspects during real patient-assisting tasks
      performed by nurses using an electric versus a hydraulic hospital bed were
      observed. While there were no differences in the flexed postures the nurses
      adopted, longer performance times were recorded when electric beds were used.
      Subjective effort, force exertion and lumbar shear forces exceeding safety limits
      proved electric beds were superior. Patients' dependency level seemed to
      influence the type of nurses' intervention (duration and force actions),
      irrespective of the bed used. The nurses greatly appreciated the electric bed.
      Its use seemed to reduce the level of effort perceived during care giving and the
      postural load during critical subtasks. Ergonomics and organizational problems
      related to adopting electric beds in hospital wards should be addressed further
      to make their use more efficient. 

PMID- 24321639
TI  - Cardiovascular strain of sawmill workers in South-Western Nigeria.
AB  - This study aimed to assess cardiovascular strain during sawmilling operations in
      terms of physical workload, based on heart rate changes. We measured resting and
      working heart rates and calculated cardiovascular load (%CVL), cardiovascular
      strain (%CVS) and relative heart rate (%RHR) in 35 sawmill workers. Based on
      heart rate only, the work in sawmills was classified as very heavy and extremely
      heavy. Similarly, a high-level category was recorded for %CVL and a very high
      range for %CVS. Thus, the workload in sawmill operations is usually very high and
      can lead to physiological strain of the workers. There is a need to redesign the
      work content of this occupation to prevent excessive strain in the workers, as
      this will increase their productivity and reduce their health risk. 

PMID- 24321640
TI  - Assessment of safety and health in the tea industry of Barak valley, Assam: a
      fuzzy logic approach.
AB  - Traditional safety and health system measurement procedures, practiced in various
      industries produce qualitative results with a degree of uncertainty. This paper
      presents a fuzzy-logic-based approach to developing a fuzzy model for assessing
      the safety and health status in the tea industry. For this, the overall safety
      and health status at a tea estate has been considered as a function of 4 inputs:
      occupational safety, occupational health, behavioral safety and competency. A set
      of fuzzy rules based on expert human judgment has been used to correlate
      different fuzzy inputs and output. Fuzzy set operations are used to calculate the
      safety and health status of the tea industry. Application of the developed model
      at a tea estate showed that the safety and health status belongs to the fuzzy
      class of good with a crisp value of 7.2. 

PMID- 24321641
TI  - Under-reporting of accidents involving biological material by nursing
      professionals at a Brazilian emergency hospital.
AB  - BACKGROUND: Pathogens can be transmitted to health professionals after contact
      with biological material. The exact number of infections deriving from these
      events is still unknown, due to the lack of systematic surveillance data and
      under-reporting. METHODS: A cross-sectional study was carried out, involving 451
      nursing professionals from a Brazilian tertiary emergency hospital between April
      and July 2009. Through an active search, cases of under-reporting of occupational
      accidents with biological material by the nursing team were identified by means
      of individual interviews. The Institutional Review Board approved the research
      project. RESULTS: Over half of the professionals (237) had been victims of one or
      more accidents (425 in total) involving biological material, and 23.76% of the
      accidents had not been officially reported using an occupational accident report.
      Among the underreported accidents, 53.47% were percutaneous and 67.33% were
      bloodborne. The main reason for nonreporting was that the accident had been
      considered low risk. CONCLUSIONS: The under-reporting rate (23.76%) was low in
      comparison with other studies, but most cases of exposure were high risk.

PMID- 24321642
TI  - Developing a questionnaire for measuring safety climate in the workplace in
      Serbia.
AB  - This study was conducted because a real method for measuring safety climate had
      never been developed and assessed in Serbian industry. The aim of this paper was
      to start the process of developing a safety climate questionnaire that could be
      used in Serbia. As a starting point a 21-item questionnaire was adopted after an
      extensive literature review. The questionnaire was distributed at several Serbian
      factories; 1098 workers responded. After a statistical analysis of the data
      obtained with the questionnaire and a critical comparison with the available
      reference results, a final questionnaire with 21 questions, divided into 7
      groups, was developed. The 7 groups of questions (factors) were safety awareness
      and competence, safety communication, organizational environment, management
      support, risk judgment and management reaction, safety precautions and accident
      prevention, and safety training. 

PMID- 24321643
TI  - Pulmonary functions of welders in gas transmission pipelines in Iran.
AB  - This study evaluated the influence of welding on pulmonary functions in welders.
      Spirometry tests were performed before and after work shift in 91 welders and 25
      clerks (control group). We examined forced vital capacity (FVC), forced
      expiratory volume in 1 s (FEV1), FEV1/FVC ratio and forced expiratory flow 25%
      75% (FEF 25-75). Significant differences were found for FVC and FEV1/FVC between
      welders and the control group in pre- and post-shift measurements (p < .001). In
      welders, smoking and nonsmoking habit had no significant effects on any pulmonary
      indices before or after shift. Work experience and fume concentrations also had
      no significant effects on the majority of spirometric indices (p > .05). Most
      welders had at least 1 of the respiratory symptoms. Significant differences were
      found between pre- and post-shift indices (as percentage of predicted values
      calculated with spirometer) and between the welders engaged in some welding tasks
      and the control group before work shift. This study documented work-related
      changes in pulmonary functions in the welders and marked drops in these functions
      without symptoms in some welders. 

PMID- 24321644
TI  - Cardiovascular load during summer work of two age groups of van-rickshaw pullers
      in West Bengal, India.
AB  - Van-rickshaw is a popular mode of transport of people and merchandise in
      developing countries. The purpose of this study was to assess the effect of age
      on cardiovascular load of van-rickshaw pullers in the summer season (March-June)
      in real situations. In 142 participants, divided into 2 age groups (25-40 and 41
      55 years), cardiovascular load was assessed on the basis of working and partial
      recovery heart rate (HR), predicted maximal HR, working maximal HR, average
      working HR, percentage of reserved HR, sum of recovery heart beats, percentage of
      recovery, relative and net cardiac cost, etc. Except for percentage of recovery,
      all parameters differed significantly between the groups and were significantly
      correlated with age. As this activity is very stressful, it places a heavy demand
      on the cardiovascular system. Therefore, age is an important factor for
      sustainability of the work, especially in a hot environment. Some ergonomic
      interventions are necessary to reduce cardiovascular load. 

PMID- 24321645
TI  - Estimation of aerobic capacity and determination of its associated factors among
      male workers of industrial sector of Iran.
AB  - INTRODUCTION: The aim of this study was to estimate maximal aerobic capacity (VO2
      max), to determine its associated factors among workers of industrial sector of
      Iran and to develop a regression equation for subjects' VO2 max. METHODS: In this
      study, 500 healthy male workers employed in Shiraz industries participated
      voluntarily. The subjects' VO2 max was assessed with the ergocycle test according
      to the Astrand protocol. Required data was collected with a questionnaire
      covering demographic details (i.e., age, job tenure, marital status, education,
      nature of work, shift work, smoking and weekly exercises). RESULTS: The subject's
      mean VO2 max was 2.69 +/- 0.263 l/min. The results showed that there was an
      association between VO2 max and age, BMI, hours of exercise and smoking, but
      there was no association between VO2 max and height, weight, nature of work and
      working schedule. On the basis of the results, regression equations were
      developed to estimate VO2 max. CONCLUSION: Final regression equation developed in
      this study may be used to estimate VO2 max reliably without the need to use other
      laboratory instruments for aerobic measurement.

PMID- 24321646
TI  - Manual material handling assessment among workers of Iranian casting workshops.
AB  - Manual material handling (MMH) tasks can be found in most workplaces and they may
      constitute a risk factor for work-related musculoskeletal disorders (WMSDs). This
      study was conducted to determine the prevalence of WMSDs and to compare MMH loads
      with the acceptable weight and force limits among Iranian casting workers. Data
      were collected from 50 workers of casting workshops who performed MMH tasks. The
      Nordic musculoskeletal disorders questionnaire and the Snook tables were used as
      tools for data collection. Hand/wrist symptoms were the most prevalent problems
      among the workers (84%). The results of the Snook tables showed that the loads in
      lifting (84%), lowering (86%), carrying (66%), pushing with initial (43%) and
      sustained force (59%), and pulling tasks with initial (48%) and sustained force
      (93%) exceeded recommended limits. WMSDs occurred in high rates among the workers
      and, thus, ergonomics interventions should focus on decreasing WMSDs and
      redesigning MMH tasks. 

PMID- 24321647
TI  - Cardiac surgery in Indigenous Australians--how wide is 'the gap'?
AB  - BACKGROUND: Cardiovascular disease remains the leading cause of mortality in the
      Indigenous Australian population. Limited research exists in regards to cardiac
      surgery in the Aboriginal and Torres Strait Islander (ATSI) population. We aimed
      to investigate risk profiles, surgical pathologies, surgical management and short
      term outcomes in a contemporary group of patients. METHODS: Variables were
      assessed for 557 consecutive patients who underwent surgery at our institution
      between August 2008 and March 2010. RESULTS: 19.2% (107/557) of patients were of
      Indigenous origin. ATSI patients were significantly younger at time of surgery
      (mean age 54.1+/-13.23 vs. 63.1+/-12.46; p=<0.001) with higher rates of
      preventable risk factors. Rheumatic heart disease (RHD) was the dominant valvular
      pathology observed in the Indigenous population. Significantly higher rates of
      left ventricular impairment and more diffuse coronary artery disease were
      observed in ATSI patients. A non-significant trend towards higher 30-day
      mortality was observed in the Indigenous population (5.6% vs. 3.1%; p=0.244).
      CONCLUSIONS: Cardiac surgery is generally required at a younger age in the
      Indigenous population with patients often presenting with more advanced disease.
      Despite often more advanced disease, surgical outcomes do not differ
      significantly from non-Indigenous patients. Continued focus on preventative
      strategies for coronary artery disease and RHD in the Indigenous population is
      required.

PMID- 24321648
TI  - Performance of risk stratification for acute coronary syndrome with two-hour
      sensitive troponin assay results.
AB  - BACKGROUND: Risk stratification processes for patients with possible acute
      coronary syndrome (ACS) recommend the use of serial sensitive troponin testing
      over at least 6h. Troponin assays vary in their analytical performance. Utility
      in accurate risk stratification at 2h post-presentation is unknown. METHODS: A
      diagnostic accuracy study of patients presenting to the emergency department (ED)
      with symptoms of ACS was performed. Troponin was measured at 0, 2 and 6h post
      presentation. Acute myocardial infarction (AMI) was adjudicated by cardiologists
      and incorporated the 0 and 6h troponin values measured by a sensitive troponin
      assay. Results were described using standard measures of test accuracy. RESULTS:
      Of the 685 patients, 51 (7.4%) had 30-day AMI or cardiac death, and 76 (11.1%)
      had secondary outcomes (all cause death, ACS and revascularisation procedures).
      There was no significant difference in the diagnostic accuracy of early versus
      late biomarker strategies when used with the current risk stratification
      processes. Incorporation of a significant delta did not improve the
      stratification at 2h post-presentation. CONCLUSIONS: Accelerated risk
      stratification of patients with ACS symptoms may occur at 2h post-presentation
      using troponin results measured by a sensitive assay. Incorporation of such a
      strategy could support improvements in patient flow within EDs.

PMID- 24321649
TI  - Effects of the antidepressant fluoxetine on the immune parameters and
      acetylcholinesterase activity of the clam Venerupis philippinarum.
AB  - Fluoxetine is an antidepressant used worldwide for the treatment of depression
      and other psychological disorders. The occurrence of fluoxetine in aquatic
      environments has been demonstrated. However, there is a lack of information about
      the effects of fluoxetine on non-target species, such as bivalve molluscs. In the
      present study, the effects of fluoxetine on the immune parameters of the clam
      Venerupis philippinarum were evaluated for the first time. Clams were exposed to
      various sublethal concentrations of fluoxetine (0, 1, 5, 25, 125, 625 MUg l-1)
      for 7 days, and the effects on the total haemocyte count (THC), the diameter and
      volume of haemocytes, haemocyte proliferation, Neutral Red uptake (NRU), and
      lysozyme activity in cell-free haemolymph (CFH) were evaluated. In addition,
      acetylcholinesterase (AChE) activity was measured in clam gills as a biomarker of
      neurotoxicity. A significant increase in THC values was observed in clams exposed
      to 25 MUg l-1 compared with controls, whereas no significant variations were
      recorded in either the diameter or the volume of haemocytes. Haemocyte
      proliferation increased significantly in animals exposed to 25, 125 and 625 MUg l
      1 compared with controls. NRU decreased significantly in the haemocytes of clams
      exposed to 1 or 5 MUg l-1, whereas NRU returned to control values in clams
      exposed to the highest fluoxetine concentrations tested (25-625 MUg l-1). No
      significant alterations were observed in CFH lysozyme activity, whereas gill AChE
      activity decreased significantly in clams exposed to 1 or 5 MUg l-1. Overall, the
      obtained results demonstrated that fluoxetine markedly affected immune parameters
      and AChE activity in clams.

PMID- 24321651
TI  - Diabetes in 2013. The new figures.

PMID- 24321688
TI  - Foam formation in a downstream digester of a cascade running full-scale biogas
      plant: Influence of fat, oil and grease addition and abundance of the filamentous
      bacterium Microthrix parvicella.
AB  - The microbial community composition in a full-scale biogas plant fed with sewage
      sludge and fat, oil and grease (FOG) was investigated over a 15-month period,
      including two foam formation events. Addition of FOG as a substrate in the biogas
      plant together with high abundances of Microthrix parvicella were found to
      promote foam formation in the downstream digester of a cascade of two biogas
      digesters. Genetic fingerprinting and quantitative PCR (qPCR) indicated a higher
      abundance of M. parvicella in the digester, when the digestion process was
      accompanied by excessive foaming relative to the reference digesters without
      disturbance. The creation of foam depended on the introduced proportion of FOG
      and the abundance of M. parvicella. Furthermore, shifts in the abundance of M.
      parvicella in the biogas plant were observed within the 15-month monitoring
      period corresponding to its seasonal abundance in the sludge of the wastewater
      treatment plant (WWTP). 

PMID- 24321689
TI  - Characterization of the Distal-less gene homologue, NlDll, in the brown
      planthopper, Nilaparvata lugens (Stal).
AB  - The brown planthopper, Nilaparvata lugens (Stal), is a globally devastating
      insect pest of rice, particularly in eastern Asia. Distal-less or Dll is a highly
      conserved and well studied transcription factor required for limb formation in
      invertebrates and vertebrates. We have identified a homologue of this gene,
      NlDll, and demonstrated that it is expressed in all life stages of N. lugens,
      particularly in adult brachypterous females. When we compared between specific
      adult tissues it was expressed most strongly in wings. Using RNAi techniques we
      demonstrated that downregulation of NlDll in the 3rd instar larvae led to the
      disrupted development of the leg, while downregulation of NlDll in the 5th instar
      larvae led to abnormal wing formation. Ectopic over-expression of NlDll in
      Drosophila melanogaster using the GAL4-UAS system led to fatal or visible
      phenotypic changes such as the loss of normal wing structure and disrupted
      haltere structure. Our work suggests that NlDll is a conserved homologue of
      Distal-less and is required for both leg development and wing structure. Since
      researches have shown that Dll is required for wing morphogenesis, understanding
      the role of NlDll during the wing development will further provide a basis for
      revealing the molecular mechanism of the wing dimorphism in brown planthopper. In
      the future, NlDll could be used as a target gene for brown planthopper pest
      management in the field. 

PMID- 24321650
TI  - From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and
      anxiety disorders.
AB  - Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a
      neutral cue to predict a biologically relevant event: after repeated predictive
      pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a
      bell, which caused them to salivate. Like sustenance, danger is biologically
      relevant, and neutral cues can take on great salience when they predict a threat
      to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD),
      this type of conditioned fear fails to extinguish, and reminders of traumatic
      events can cause pathological conditioned fear responses for decades after danger
      has passed. In this review, we use fear conditioning and extinction studies to
      draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain
      how rodent studies have informed neuroimaging studies of healthy humans and
      humans with PTSD. We describe several genes that have been linked to both PTSD
      and fear conditioning and extinction and explain how abnormalities in fear
      conditioning or extinction may reflect a general biomarker of anxiety disorders.
      Finally, we explore drug and neuromodulation treatments that may enhance
      therapeutic extinction in anxiety disorders.

PMID- 24321691
TI  - Establishment of a rapid, inexpensive protocol for extraction of high quality RNA
      from small amounts of strawberry plant tissues and other recalcitrant fruit
      crops.
AB  - Strawberry plant tissues and particularly fruit material are rich in
      polysaccharides and polyphenolic compounds, thus rendering the isolation of
      nucleic acids a difficult task. This work describes the successful modification
      of a total RNA extraction protocol, which enables the isolation of high quantity
      and quality of total RNA from small amounts of strawberry leaf, root and fruit
      tissues. Reverse-transcription polymerase chain reaction (RT-PCR) amplification
      of GAPDH housekeeping gene from isolated RNA further supports the proposed
      protocol efficiency and its use for downstream molecular applications. This novel
      procedure was also successfully followed using other fruit tissues, such as olive
      and kiwifruit. In addition, optional treatment with RNase A following initial
      nucleic acid extraction can provide sufficient quality and quality of genomic DNA
      for subsequent PCR analyses, as evidenced from PCR amplification of housekeeping
      genes using extracted genomic DNA as template. Overall, this optimized protocol
      allows easy, rapid and economic isolation of high quality RNA from small amounts
      of an important fruit crop, such as strawberry, with extended applicability to
      other recalcitrant fruit crops. 

PMID- 24321690
TI  - Comparative gene expression analysis of Dtg, a novel target gene of Dpp signaling
      pathway in the early Drosophila melanogaster embryo.
AB  - In the early Drosophila melanogaster embryo, Dpp, a secreted molecule that
      belongs to the TGF-beta superfamily of growth factors, activates a set of
      downstream genes to subdivide the dorsal region into amnioserosa and dorsal
      epidermis. Here, we examined the expression pattern and transcriptional
      regulation of Dtg, a new target gene of Dpp signaling pathway that is required
      for proper amnioserosa differentiation. We showed that the expression of Dtg was
      controlled by Dpp and characterized a 524-bp enhancer that mediated expression in
      the dorsal midline, as well as, in the differentiated amnioserosa in transgenic
      reporter embryos. This enhancer contained a highly conserved region of 48-bp in
      which bioinformatic predictions and in vitro assays identified three Mad binding
      motifs. Mutational analysis revealed that these three motifs were necessary for
      proper expression of a reporter gene in transgenic embryos, suggesting that short
      and highly conserved genomic sequences may be indicative of functional regulatory
      regions in D. melanogaster genes. Dtg orthologs were not detected in basal
      lineages of Dipterans, which unlike D. melanogaster develop two extra-embryonic
      membranes, amnion and serosa, nevertheless Dtg orthologs were identified in the
      transcriptome of Musca domestica, in which dorsal ectoderm patterning leads to
      the formation of a single extra-embryonic membrane. These results suggest that
      Dtg was recruited as a new component of the network that controls dorsal ectoderm
      patterning in the lineage leading to higher Cyclorrhaphan flies, such as D.
      melanogaster and M. domestica. 

PMID- 24321692
TI  - The goldfish hAT-family transposon Tgf2 is capable of autonomous excision in
      zebrafish embryos.
AB  - The goldfish (Carassius auratus) Tgf2 transposon is a vertebrate DNA transposon
      that belongs to the hAT transposon family. In this study, we constructed plasmids
      containing either the full-length Tgf2 transposon (pTgf2 plasmid) or a partially
      deleted Tgf2 transposon (DeltapTgf2 plasmid), and microinjected these plasmids
      into fertilized zebrafish (Danio rerio) eggs at the one- to two-cell stage. DNA
      extracted from the embryos was analyzed by PCR to assess transient excision, if
      any, of the exogenous plasmid and to verify whether Tgf2 is an autonomous
      transposon. The results showed that excision-specific bands were not detected in
      embryos injected with the DeltapTgf2 plasmid, while bands of 300-500bp were
      detected in embryos injected with pTgf2, which indicated that the full-length
      Tgf2-containing plasmid could undergo autonomous excision in zebrafish embryos.
      DNA cloned from 24 embryos injected with pTgf2 was sequenced, and the results
      suggested that Tgf2 underwent self-excision in zebrafish embryos. Cloning and PCR
      analysis of DNA extracted from embryos co-injected with DeltapTgf2 and in vitro
      transcribed transposase mRNA indicated that partially-deleted-Tgf2-containing
      DeltapTgf2 plasmid also underwent excision, in the presence of functional
      transposase mRNA. DNA cloned from 25 embryos co-injected with DeltapTgf2 and
      transposase mRNA was sequenced, and the results suggested that partially-deleted
      Tgf2 transposons plasmids were excised. These results demonstrated that excisions
      of Tgf2 transposons were mediated by the Tgf2 transposase, which in turn
      confirmed that Tgf2 is an autonomous transposon. 

PMID- 24321693
TI  - Differential gene expression in Giardia lamblia under oxidative stress:
      significance in eukaryotic evolution.
AB  - Giardia lamblia is a unicellular, early branching eukaryote causing giardiasis,
      one of the most common human enteric diseases. Giardia, a microaerophilic
      protozoan parasite has to build up mechanisms to protect themselves against
      oxidative stress within the human gut (oxygen concentration 60 MUM) to establish
      its pathogenesis. G. lamblia is devoid of the conventional mechanisms of the
      oxidative stress management system, including superoxide dismutase, catalase,
      peroxidase, and glutathione cycling, which are present in most eukaryotes. NADH
      oxidase is a major component of the electron transport chain of G. lamblia, which
      in concurrence with disulfide reductase, protects oxygen-labile proteins such as
      pyruvate: ferredoxin oxidoreductase against oxidative stress by sustaining a
      reduced intracellular environment. It also contains the arginine dihydrolase
      pathway, which occurs in a number of anaerobic prokaryotes, includes substrate
      level phosphorylation and adequately active to make a major contribution to ATP
      production. To study differential gene expression under three types of oxidative
      stress, a Giardia genomic DNA array was constructed and hybridized with labeled
      cDNA of cells with or without stress. The transcriptomic data has been analyzed
      and further validated using real time PCR. We identified that out of 9216 genes
      represented on the array, more than 200 genes encoded proteins with functions in
      metabolism, oxidative stress management, signaling, reproduction and cell
      division, programmed cell death and cytoskeleton. We recognized genes modulated
      by at least >= 2 fold at a significant time point in response to oxidative
      stress. The study has highlighted the genes that are differentially expressed
      during the three experimental conditions which regulate the stress management
      pathway differently to achieve redox homeostasis. Identification of some unique
      genes in oxidative stress regulation may help in new drug designing for this
      common enteric parasite prone to drug resistance. Additionally, these data
      suggest the major role of this early divergent ancient eukaryote in anaerobic to
      aerobic organism evolution.

PMID- 24321694
TI  - Two Y chromosomes with duplication of the distal long arm including the entire
      AZFc region.
AB  - Chromosome anomalies/rearrangements of the Y chromosome seldom threaten life and
      are quite common. The 4.5 Mb AZFc region on Yq11.2 is one of the most polymorphic
      regions in the human genome. AZFc partial deletion is almost inevitably
      associated with impaired fertility while the functional significance of AZFc
      partial duplications remains controversial. In this report, a large Y chromosome
      with one centromere and two heterochromatic blocks was identified incidentally in
      two men. The first case was ascertained through surveillance for recurrent
      miscarriage. The second case was ascertained through amniocytes of a fetus and
      his father. FISH and array-based comparative genomic hybridization showed
      duplications of the entire AZFc region as well as Yq euchromatic region. The
      duplications in Case 1 and Case 2 spanned 4.8 Mb and 6.2 Mb, respectively, of the
      Yq euchromatic region. These two cases suggest that complete AZFc duplication
      could be completely benign. It awaits further investigation whether this is a
      bona fide chromosomal polymorphism.

PMID- 24321695
TI  - Do offenders and victims drink for different reasons? Testing mediation of
      drinking motives in the link between bullying subgroups and alcohol use in
      adolescence.
AB  - OBJECTIVES: Previous studies have reported inconsistent evidence on associations
      between adolescents involved in different bullying subgroups (victims, offenders
      and offender-victims) and alcohol use. In addition, little is known about the
      underlying mechanisms between these bullying subgroups and alcohol use. The aim
      of this study was to clarify the association between the different bullying
      subgroups and alcohol use by investigating whether it is mediated by drinking
      motives. METHODS: Structural equation models were estimated based on a nationally
      representative sample of 2548 alcohol-experienced 12 to 17-year-olds who
      participated in the 2010 Health Behaviour in School-Aged Children survey in
      Switzerland. RESULTS: Consistent for both alcohol outcomes (drunkenness and
      drinking volume), male and female offenders presented higher levels of alcohol
      use than those not involved in bullying, not only per se (direct link) but also
      due to higher levels of enhancement and social drinking motives (indirect link).
      Victims, meanwhile, presented lower levels of alcohol use through an indirect
      link, with lower levels of enhancement (boys and girls) and social motives
      (boys). The higher levels of alcohol use among offender-victims were mediated by
      all four drinking motives among girls, and in particular by coping motives among
      boys. CONCLUSIONS: In most cases, different levels of alcohol use in the bullying
      subgroups are due to differences in drinking motives. For prevention, it is
      important to take account of the differences in drinking motives and problems of
      offenders, victims and offender-victims.

PMID- 24321696
TI  - Small financial incentives increase smoking cessation in homeless smokers: a
      pilot study.
AB  - Although over 70% of homeless individuals smoke, few studies have examined the
      effectiveness of smoking cessation interventions in this vulnerable population.
      The purpose of this pilot study was to compare the effectiveness of shelter-based
      smoking cessation clinic usual care (UC) to an adjunctive contingency management
      (CM) treatment that offered UC plus small financial incentives for smoking
      abstinence. Sixty-eight homeless individuals in Dallas, Texas (recruited in 2012)
      were assigned to UC (n=58) or UC plus financial incentives (CM; n=10) groups and
      were followed for 5 consecutive weeks (1 week pre-quit through 4 weeks post
      quit). A generalized linear mixed model regression analysis was conducted to
      compare biochemically-verified abstinence rates between groups. An additional
      model examined the interaction between time and treatment group. The participants
      were primarily male (61.8%) and African American (58.8%), and were 49 years of
      age on average. There was a significant effect of treatment group on abstinence
      overall, and effects varied over time. Follow-up logistic regression analyses
      indicated that CM participants were significantly more likely than UC
      participants to be abstinent on the quit date (50% vs. 19% abstinent) and at 4
      weeks post-quit (30% vs. 1.7% abstinent). Offering small financial incentives for
      smoking abstinence may be an effective way to facilitate smoking cessation in
      homeless individuals.

PMID- 24321697
TI  - Situational determinants of use and treatment outcomes in marijuana dependent
      adults.
AB  - Research and theory strongly support the importance of situational determinants
      of substance use as targets for intervention, but few studies have systematically
      examined situational use characteristics in marijuana dependent adults. The
      present study describes situational use of marijuana in a population of 87
      marijuana dependent adults and reports relationships with outcomes of treatment.
      Use in negative affective situations was independently associated with
      psychological distress, maladaptive coping strategies, lower self-efficacy, and
      poorer outcomes post-treatment. The findings were consistent with research on
      using drugs to cope with negative affect providing evidence of convergence
      between two different methods of assessing high risk situations for substance
      use. The results support continued emphasis on coping with negative affect as a
      target in treatments for marijuana dependence. 

PMID- 24321698
TI  - QSAR, docking, dynamic simulation and quantum mechanics studies to explore the
      recognition properties of cholinesterase binding sites.
AB  - A set of 84 known N-aryl-monosubstituted derivatives (42 amides: series 1 and 2,
      and 42 imides: series 3 an 4, from maleic and succinic anhydrides, respectively)
      that display inhibitory activity toward both acetylcholinesterase and
      butyrylcholinesterase (ChEs) was considered for Quantitative structure-activity
      relationship (QSAR) studies. These QSAR studies employed docking data from both
      ChEs that were previously submitted to molecular dynamics (MD) simulations.
      Donepezil and galanthamine stereoisomers were included to analyze their quantum
      mechanics properties and for validating the docking procedure. Quantum parameters
      such as frontier orbital energies, dipole moment, molecular volume, atomic
      charges, bond length and reactivity parameters were measured, as well as
      partition coefficients, molar refractivity and polarizability were also analyzed.
      In order to evaluate the obtained equations, four compounds: 1a (4-oxo-4
      (phenylamino)butanoic acid), 2a ((2Z)-4-oxo-4-(phenylamino)but-2-enoic acid), 3a
      (2-phenylcyclopentane-1,3-dione) and 4a (2-phenylcyclopent-4-ene-1,3-dione) were
      employed as independent data set, using only equations with r(m(test))2>0.5. It
      was observed that residual values gave low value in almost all series, excepting
      in series 1 for compounds 3a and 4a, and in series 4 for compounds 1a, 2a and 3a,
      giving a low value for 4a. Consequently, equations seems to be specific according
      to the structure of the evaluated compound, that means, series 1 fits better for
      compound 1a, series 3 or 4 fits better for compounds 3a or 4a. Same behavior was
      observed in the butyrylcholinesterase (BChE). Therefore, obtained equations in
      this QSAR study could be employed to calculate the inhibition constant (Ki) value
      for compounds having a similar structure as N-aryl derivatives described here.
      The QSAR study showed that bond lengths, molecular electrostatic potential and
      frontier orbital energies are important in both ChE targets. Docking studies
      revealed that despite the multiple conformations obtained through MD simulations
      on both ChEs, the ligand recognition properties were conserved. In fact, the
      complex formed between ChEs and the best N-aryl compound reproduced the binding
      mode experimentally reported, where the ligand was coupled into the choline
      binding site and stabilized through pi-pi interactions with Trp82 or Trp86 for
      BChE and AChE, respectively, suggesting that this compound could be an efficient
      inhibitor and supporting our model.

PMID- 24321699
TI  - Spatial reorganisation of muscle activity correlates with change in tangential
      force variability during isometric contractions.
AB  - The aim of this study was to quantify the effects of spatial reorganisation of
      muscle activity on task-related and tangential components of force variability
      during sustained contractions. Three-dimensional forces were measured from
      isometric elbow flexion during submaximal contractions (50s, 5-50% of maximal
      voluntary contraction (MVC)) and total excursion of the centre of pressure was
      extracted. Spatial electromyographic (EMG) activity was recorded from the biceps
      brachii muscle. The centroids of the root mean square (RMS) EMG and normalised
      mutual information (NMI) maps were computed to assess spatial muscle activity and
      spatial relationship between EMG and task-related force variability,
      respectively. Result showed that difference between the position of the centroids
      at the beginning and at the end of the contraction of the RMS EMG and the NMI
      maps were different in the medial-lateral direction (P<0.05), reflecting that
      muscle regions modulate their activity without necessarily modulating the
      contribution to the task-related force variability over time. Moreover, this
      difference between shifts of the centroids was positively correlated with the
      total excursion of the centre of pressure at the higher levels of contractions
      (>30% MVC, R(2)>0.30, P<0.05), suggesting that changes in spatial muscle activity
      could impact on the modulation of tangential forces. Therefore, within-muscle
      adaptations do not necessarily increase force variability, and this interaction
      can be quantified by analysing the RMS EMG and the NMI map centroids. 

PMID- 24321700
TI  - Inter-individual variation in reciprocal Ia inhibition is dependent on the
      descending volleys delivered from corticospinal neurons to Ia interneurons.
AB  - INTRODUCTION: We investigated the extent to which the corticospinal inputs
      delivered to Ia inhibitory interneurons influence the strength of disynaptic
      reciprocal Ia inhibition. METHODS: Seventeen healthy subjects participated in
      this study. The degree of reciprocal Ia inhibition was determined via short
      latency (condition-test interval: 1-3ms) suppression of Sol H-reflex by
      conditioning stimulation of common peroneal nerve. The effect of corticospinal
      descending inputs on Ia inhibitory interneurons was assessed by evaluating the
      conditioning effect of transcranial magnetic stimulation (TMS) on the Sol H
      reflex. Then, we determined the relationship between the degree of reciprocal Ia
      inhibition and the conditioning effect of TMS on the Sol H-reflex. RESULT: We
      found that the degree of reciprocal Ia inhibition and the extent of change in the
      amplitude of the TMS-conditioned H-reflex, which was measured from short latency
      facilitation to inhibition, displayed a strong correlation (r=0.76, p<0.01) in
      the resting conditions. CONCLUSION: The extent of reciprocal Ia inhibition is
      affected by the corticospinal descending inputs delivered to Ia inhibitory
      interneurons, which might explain the inter-individual variations in reciprocal
      Ia inhibition.

PMID- 24321701
TI  - The Colorado LEAP study: rationale and design of a study to assess the short term
      longitudinal effectiveness of a preschool nutrition and physical activity
      program.
AB  - BACKGROUND: The preschool years are a critical window for obesity prevention
      efforts; representing a time when children establish healthy eating habits and
      physical activity patterns. Understanding the context in which these behaviors
      develop is critical to formulating a model to address childhood obesity. The
      Colorado LEAP Study, an intervention study designed to prevent early childhood
      obesity, utilizes a social ecological approach to explore individual, family and
      environmental factors and their relationship to child weight status over a 3 year
      timeframe. METHODS: The study is located in 5 rural Colorado preschool centers
      and elementary schools (2 treatment and 3 control). Treatment sites receive The
      Food Friends nutrition (12 weeks) and physical activity (18 weeks) interventions
      during preschool. Observational measures assess 3 layers of the social ecological
      model including individual, family and organizational inputs. Children's food
      preferences, food intake, gross motor skills, physical activity
      (pedometers/accelerometers), cognitive, physical and social self-competence and
      height/weight are collected. Parents provide information on feeding and activity
      practices, child's diet, oral sensory characteristics, food neophobia, home food
      and activity environment, height/weight and physical activity (pedometers).
      School personnel complete a school environment and policy assessment.
      Measurements are conducted with 3 cohorts at 4 time points - baseline, post
      intervention, 1- and 2-year follow-up. DISCUSSION: The design of this study
      allows for longitudinal exploration of relationships among eating habits,
      physical activity patterns, and weight status within and across spheres of the
      social ecological model. These methods advance traditional study designs by
      allowing not only for interaction among spheres but predictively across time.
      Further, the recruitment strategy includes both boys and girls from ethnic
      minority populations in rural areas and will provide insights into obesity
      prevention effects on these at risk populations. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01937481.

PMID- 24321702
TI  - Spectrometric analysis of mercury content in 549 skin-lightening products: is
      mercury toxicity a hidden global health hazard?
AB  - BACKGROUND: Cosmetic skin lightening is practiced worldwide. Mercury is a well
      documented melanotoxin added to some lightening products. However, mercury can
      cause many dermatologic, renal, and neurologic problems. The Food and Drug
      Administration limits the amount of mercury in cosmetic products to trace
      amounts, 1 ppm. OBJECTIVE: The objective of this study was to quantitatively
      evaluate a large international sample of lightening products for mercury content,
      focusing on products available to US consumers either online or in stores.
      METHODS: A total of 549 skin-lightening products, manufactured in 32 countries,
      were purchased online in the United States, Taiwan, and Japan and in stores in
      the United States, China, Taiwan, Thailand, Japan, and Sri Lanka. Cosmetics were
      screened for mercury content above 200 ppm using a low-cost portable x-ray
      fluorescence spectrometer. RESULTS: Of the 549 tested products, 6.0% (n = 33)
      contained mercury above 1000 ppm. In all, 45% of mercury-containing samples
      contained mercury in excess of 10,000 ppm. Of lightening products purchased in
      the United States, 3.3% were found to contain mercury in excess of 1000 ppm.
      LIMITATIONS: Our study did not evaluate creams for other melanosuppressive
      ingredients. Only 1 sample of each product was tested. CONCLUSION: Our study
      confirms the national and global presence of mercury in skin-lightening products.

PMID- 24321703
TI  - Non-HFE hemochromatosis: pathophysiological and diagnostic aspects.
AB  - Rare genetic iron overload diseases are an evolving field due to major advances
      in genetics and molecular biology. Genetic iron overload has long been confined
      to the classical type 1 hemochromatosis related to the HFE C282Y mutation.
      Breakthroughs in the understanding of iron metabolism biology and molecular
      mechanisms led to the discovery of new genes and subsequently, new types of
      hemochromatosis. To date, four types of hemochromatosis have been identified: HFE
      related or type1 hemochromatosis, the most frequent form in Caucasians, and four
      rare types, named type 2 (A and B) hemochromatosis (juvenile hemochromatosis due
      to hemojuvelin and hepcidin mutation), type 3 hemochromatosis (related to
      transferrin receptor 2 mutation), and type 4 (A and B) hemochromatosis
      (ferroportin disease). The diagnosis relies on the comprehension of the involved
      physiological defect that can now be explored by biological and imaging tools,
      which allow non-invasive assessment of iron metabolism. A multidisciplinary
      approach is essential to support the physicians in the diagnosis and management
      of those rare diseases. 

PMID- 24321704
TI  - Identification of vaccine-derived polioviruses using dual-stage real-time RT-PCR.
AB  - Vaccine-derived polioviruses (VDPVs) are associated with polio outbreaks and
      prolonged infections in individuals with primary immunodeficiencies. VDPV
      specific PCR assays for each of the three Sabin oral poliovirus vaccine (OPV)
      strains were developed, targeting sequences within the VP1 capsid region that are
      selected for during replication of OPV in the human intestine. Over 2400 Sabin
      related isolates and identified 755 VDPVs were screened. Sensitivity of all
      assays was 100%, while specificity was 100% for serotypes 1 and 3, and 76% for
      serotype 2. The assays permit rapid, sensitive identification of OPV-related
      viruses and flag programmatically important isolates for further characterization
      by genomic sequencing. 

PMID- 24321705
TI  - Cyclospora infection in a young woman with human immunodeficiency virus in Hong
      Kong: a case report.
AB  - BACKGROUND: Cyclospora is an uncommon pathogen. The diagnosis of Cyclospora
      infection can be difficult because of its scarcity in developed countries,
      intracellular mode of life, small size of the parasite and its inability to take
      up routine microscopic stains. However, it is endemic in many countries in Asia,
      Africa, Central and South America. With the increase in travels to these areas,
      the number of cases is expected to increase. Moreover, it is found to be
      associated with numerous food-borne outbreaks. CASE PRESENTATION: We encountered
      a patient with human immunodeficiency virus presented with 6 months of diarrhoea.
      The initial investigation was unrevealing. The diagnosis of Cyclospora infection
      was finally made on the histological sample obtained by colonoscopy. Moreover,
      the initial therapy with ciprofloxacin was not effective, while
      trimethoprim/sulfamethoxazole resulted in final cure of the disease. CONCLUSION:
      Travel and food histories are important for the suspicion of Cyclospora
      infection. Histological examination is more sensitive in making a diagnosis of
      Cyclospora infection of the gut than fecal microscopic examination.
      Trimethoprim/sulfamethoxazole is a more reliable therapy for Cyclospora infection
      in patients with human immunodeficiency virus.

PMID- 24321706
TI  - The effect of dose on rhBMP-2 signaling, delivered via collagen sponge, on
      osteoclast activation and in vivo bone resorption.
AB  - While recombinant human bone morphogenetic protein (rhBMP)-2-based bone therapy
      presents potential osteoinductivity, it also leads concern due to transient
      osteoclast activation during early healing periods, ultimately limiting its
      clinical use. Therefore, we investigated in vivo and in vitro rhBMP-2 signaling
      which mediates early bone resorbing effect, depending on the dose, and attempted
      to inhibit this resorption phenomenon using NFAT inhibitor as a target molecule.
      High-dose of rhBMP-2 (20 MUg/defect) enhanced osteoclast activation and the
      expression of bone resorption markers, compared to low dose (5 MUg/defect) at one
      week after surgery in collagen sponge-delivered rat calvarial defect models.
      Interestingly, this trend was also observed in the expression of bone formation
      markers. In particular, rhBMP-2 upregulated RANKL expression, while it
      downregulated osteoprotegerin (OPG) expression, resulting in a dose-dependent
      increase in the ratio of RANKL to OPG. NFAT inhibitor (150 MUm) treatment in vivo
      suppressed the high-dose effect of rhBMP-2 on both resorption and formation. In
      vitro results of rhBMP-2 signaling and NFAT inhibitor effects in rat mesenchymal
      stem cells showed similar trends as in vivo results. Microcomputer tomography
      based evaluation at 4 weeks showed that combined treatment of NFAT inhibitor with
      20 MUg rhBMP-2 in vivo increased bone volume (BV) more than 20 MUg rhBMP-2 alone,
      which showed little difference in BV compared to 5 MUg of rhBMP-2. These results
      demonstrated that rhBMP-2 implantation concurrently signalized into enhanced
      osteoclastogenesis and osteoblastogenesis in vivo, dose-dependently. Ratio of
      RANKL/OPG might be an index for early bone resorbing activity of implanted rhBMP
      2. A local cocktail treatment of NFAT inhibitor and high-dose rhBMP-2 might be an
      alternative to overcome early bone resorbing effects, thereby accelerating bone
      formation.

PMID- 24321707
TI  - Preservation of aortic root architecture and properties using a detergent
      enzymatic perfusion protocol.
AB  - Aortic valve degeneration and dysfunction is one of the leading causes for
      morbidity and mortality. The conventional heart-valve prostheses have significant
      limitations with either life-long anticoagulation therapeutic associated bleeding
      complications (mechanical valves) or limited durability (biological valves).
      Tissue engineered valve replacement recently showed encouraging results, but the
      unpredictable outcome of tissue degeneration is likely associated to the
      extensive tissue processing methods. We believe that optimized decellularization
      procedures may provide aortic valve/root grafts improved durability. We present
      an improved/innovative decellularization approach using a detergent-enzymatic
      perfusion method, which is both quicker and has less exposure of matrix
      degenerating detergents, compared to previous protocols. The obtained graft was
      characterized for its architecture, extracellular matrix proteins, mechanical and
      immunological properties. We further analyzed the engineered aortic root for
      biocompatibility by cell adhesion and viability in vitro and heterotopic
      implantation in vivo. The developed decellularization protocol was substantially
      reduced in processing time whilst maintaining tissue integrity. Furthermore, the
      decellularized aortic root remained bioactive without eliciting any adverse
      immunological reaction. Cell adhesion and viability demonstrated the scaffold's
      biocompatibility. Our optimized decellularization protocol may be useful to
      develop the next generation of clinical valve prosthesis with a focus on improved
      mechanical properties and durability.

PMID- 24321708
TI  - A tetracycline expression system in combination with Sox9 for cartilage tissue
      engineering.
AB  - Cartilage tissue engineering using controllable transcriptional therapy together
      with synthetic biopolymer scaffolds shows higher potential for overcoming
      chondrocyte degradation and constructing artificial cartilages both in vivo and
      in vitro. Here, the potential regulating tetracycline expression (Tet-on) system
      was used to express Sox9 both in vivo and in vitro. Chondrocyte degradation was
      measured in vitro and overcome by Soxf9 expression. Experiments confirmed the
      feasibility of the combined use of Sox9 and Tet-on system in cartilage tissue
      engineering. Engineered poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)
      scaffolds were seeded with recombinant chondrocytes which were transfected with
      Tet-induced Sox9 expression; the scaffolds were implanted under the skin of 8
      week-old rats. The experimental group was injected with Dox in the abdomen, while
      the control group was injected with normal saline. After 4 or 8 days of
      implantation in vivo, the newly formed pieces of articular chondrocytes were
      taken out and measured. Dox injection in vivo showed positive effect on
      recombinant chondrocytes, in which Sox9 expression was up-regulated by an
      inducible system with specific matrix proteins. The results demonstrate this
      controllable transcriptional therapy is a potential approach for tissue
      engineering.

PMID- 24321709
TI  - The effects of artificial E-cadherin matrix-induced embryonic stem cell
      scattering on paxillin and RhoA activation via alpha-catenin.
AB  - Mechanical forces have been shown to affect stem cell behavior in a large array
      of ways. However, our understanding of how these mechanical cues may regulate the
      behavior of embryonic stem cells (ESCs) remains in its infancy. Here, we aim to
      clarify the effect of cell scattering on the regulation of Rho family GTPases
      Rac1 and RhoA as well as paxillin. Allowing ESCs to spread and scatter on a
      synthetically designed E-cadherin substratum causes phosphorylation of paxillin
      on consensus phosphorylation sites leading to activation of Rac1 and inactivation
      of RhoA. By culturing cells in presence of RhoA activator or growing cells to a
      highly confluent state reverses the effect of cell scattering phenotype.
      Knockdown of E-cadherin-adapter protein alpha-catenin revealed that it negatively
      affects paxillin phosphorylation and up-regulates RhoA activity in compact
      cellular aggregates. Collectively these results indicate that cell scattering
      might cause a conformational change of alpha-catenin limiting its capacity to
      inhibit paxillin phosphorylation that causes an increase in Rac1 activation and
      RhoA deactivation. Understanding how synthetically designed extracellular matrix
      affect ESC signaling through mechanical cues brings a new aspect for stem cell
      engineers to develop technologies for controlling cell function. 

PMID- 24321710
TI  - MATRICS cognitive consensus battery (MCCB) performance in children, adolescents,
      and young adults.
AB  - BACKGROUND: Neurodevelopmental models of schizophrenia suggest that cognitive
      deficits may be observed during childhood and adolescence, long before the onset
      of psychotic symptoms. Elucidating the trajectory of normal cognitive development
      during childhood and adolescence may therefore provide a basis for identifying
      specific abnormalities related to the development of schizophrenia. The MATRICS
      Consensus Cognitive Battery (MCCB), which was designed for use in clinical trials
      targeting cognitive deficits most common in schizophrenia, may provide a
      mechanism to understand this trajectory. To date, however, there is no
      performance data for the MCCB in healthy children and adolescents. The present
      study sought to establish performance data for the MCCB in healthy children,
      adolescents, and young adults. METHODS: The MCCB was administered to a community
      sample of 190 healthy subjects between the ages of 8 and 23years. All MCCB domain
      scores were converted to T-scores using sample means and standard deviations and
      were compared for significant performance differences between sex and age strata.
      RESULTS: Analyses revealed age effects following quadratic trends in all MCCB
      domains, which is consistent with research showing a leveling off of childhood
      cognitive improvement upon approaching late adolescence. Sex effects after
      controlling for age only presented for one MCCB domain, with males exhibiting
      well-known spatial reasoning advantages. CONCLUSIONS: Utilizing this performance
      data may aid future research seeking to elucidate specific deficits that may be
      predictive of later development of SZ.

PMID- 24321712
TI  - The relationship between insight and theory of mind in schizophrenia.
AB  - INTRODUCTION: It has been proposed that theory of mind (ToM) deficits underlying
      difficulties in taking the perspective of others may substantially contribute to
      insight impairment in schizophrenia. The present study aimed to explore the
      effect of ToM deficits on insight impairment independently of co-existent
      neurocognitive deficits and symptom severity in chronic schizophrenia. METHODS:
      Fifty-eight chronic patients with schizophrenia and 56 matched healthy
      participants were assessed with the Schedule for the Assessment of Insight (SAI
      E) along with a series of ToM tasks and a comprehensive battery of
      neuropsychological measures. Symptoms were measured with the Positive and
      Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia.
      RESULTS: ToM impairment explained a substantial proportion of variance in overall
      insight and its three major components: awareness of illness, relabelling of
      symptoms and treatment compliance. Moreover, the effect of ToM deficits on
      insight remained significant even after controlling for all neurocognitive
      factors and symptom ratings. Regression analysis showed that symptoms and
      cognitive deficits also contribute to impaired insight in schizophrenia. General
      intellectual ability was negatively associated with both overall insight and
      relabelling of symptoms. Executive functions were negatively associated with
      relabelling. CONCLUSION: Our findings confirm that ToM deficits negatively affect
      insight independently of neurocognitive deficits and symptom severity in chronic
      schizophrenia. The effect of ToM deficits on insight should be further examined
      in the broader context of the failures in metacognition and their relationships
      with insight impairment in schizophrenia.

PMID- 24321713
TI  - Physical activity, exercise and diabetes.

PMID- 24321711
TI  - White matter abnormalities in 22q11.2 deletion syndrome: preliminary associations
      with the Nogo-66 receptor gene and symptoms of psychosis.
AB  - BACKGROUND: This study utilized diffusion tensor imaging (DTI) to analyze white
      matter tractography in the anterior limb of the internal capsule (ALIC), fornix,
      and uncinate fasciculus (UF) of individuals with 22q11.2 deletion syndrome and
      controls. Aberrations in these tracts have been previously associated with
      schizophrenia. With up to 25% of individuals with 22q11.2DS developing
      schizophrenia in adulthood, we hypothesized reduction in structural integrity of
      these tracts, including an association with prodromal symptoms of psychosis. We
      further predicted an association between allelic variation in a functional
      polymorphism of the Nogo-66 receptor gene and 22q11.2DS white matter integrity.
      METHODS: Tractography was conducted using fiber assignment by streamline tracking
      algorithm in DTI Studio. Subjects were genotyped for the rs701428 SNP of the Nogo
      66 receptor gene, and assessed for presence of prodromal symptoms. RESULTS: We
      found significant group differences between 22q11.2DS and controls in DTI metrics
      for all three tracts. DTI metrics of ALIC and UF were associated with prodromal
      symptoms in 22q11.2DS. Further, ALIC DTI metrics were associated with allelic
      variation of the rs701428 SNP of the Nogo-66 receptor gene in 22q11.2DS.
      CONCLUSIONS: Alterations in DTI metrics suggest white matter microstructural
      anomalies of the ALIC, fornix, and UF in 22q11.2DS. Structural differences in
      ALIC appear to be associated with the Nogo-66 receptor gene, which has been
      linked to myelin-mediated axonal growth inhibition. Moreover, the association
      between psychosis symptoms and ALIC and UF metrics suggests that the Nogo-66
      receptor gene may represent a susceptibility gene for psychosis through its
      disruption of white matter microstructure and myelin-associated axonal growth.

PMID- 24321714
TI  - The year in review: time to celebrate.

PMID- 24321715
TI  - Physical activity clinical practice guidelines: what's new in 2013?

PMID- 24321716
TI  - Exercise facilitators and barriers from adoption to maintenance in the diabetes
      aerobic and resistance exercise trial.
AB  - OBJECTIVE: We conducted a qualitative investigation of patients with type 2
      diabetes to determine their perceived facilitators and barriers to exercise at
      multiple time points while enrolled in a randomized exercise trial including
      aerobic, resistance or combined exercise. We explored differences in these themes
      over time, between intervention groups and by adherence level after intervention.
      METHODS: Interviews were conducted by telephone at 3 weeks (run-in period), and
      at 3 (midintervention), 6 (end of intervention) and 9 months (maintenance) after
      enrollment to assess factors that facilitated and hampered adherence to the
      exercise program. Audiotapes were transcribed verbatim and subjected to content
      analysis. RESULTS: Participants (n=28) with type 2 diabetes engaged in the
      interviews. Social support from family and the trainer, future health benefits, a
      sense of well-being and perceived fitness improvements were exercise
      facilitators. Experiencing illness or injury, work commitments and inclement
      weather were highlighted barriers. A sense of well-being, fitness improvements
      and enjoyment frequently were expressed by participants assigned to the combined
      and resistance exercise conditions. Participants who maintained prescribed
      exercise levels tended to be engaged in resistance exercise, and spoke of support
      from their personal trainers, the importance of strategies and enjoyment more
      frequently than those who did not maintain their exercise level. Exercise
      maintainers also cited more facilitators; no differences were found for barriers.
      CONCLUSIONS: Patients with type 2 diabetes require social support, including
      continued contact with exercise specialists. Patients need assistance with
      motivational enhancement and strategies to increase facilitators to maintain
      exercise behaviour. Incorporating resistance exercise improves well-being and
      enjoyment-2 important factors linked to exercise maintenance.

PMID- 24321717
TI  - Effects of aerobic exercise with or without metformin on plasma incretins in type
      2 diabetes.
AB  - OBJECTIVE: Despite positive effects of incretins on insulin secretion, little is
      known about the effect of exercise on these hormones. Metformin can affect
      incretin concentrations and is prescribed to a large proportion of people with
      diabetes. We, therefore, examined the effects of aerobic exercise and/or
      metformin on incretin hormones. METHODS: Ten participants with type 2 diabetes
      were recruited for this randomized crossover study. Metformin or placebo was
      given for 28 days, followed by the alternate treatment for 28 days. On the last 2
      days of each condition, participants were assessed during a non-exercise day and
      a subsequent exercise day. Aerobic exercise took place in the morning and blood
      samples were taken in the subsequent hours (before and after lunch). RESULTS:
      Aerobic exercise did not increase total plasma glucagon-like peptide-1 (GLP-1) or
      glucose-dependent insulinotropic polypeptide (GIP) in the pre- or post-lunch
      periods (all p>0.1). GLP-1 was higher in the pre-lunch (p=0.016) and post-lunch
      (p=0.018) periods of the metformin conditions compared with the placebo. Total
      plasma GIP was higher in the pre-lunch period (p=0.05), but not in the post-lunch
      period (p=0.95), with metformin compared with placebo. CONCLUSIONS: In contrast
      to our hypothesis, aerobic exercise did not acutely increase total GLP-1 and GIP
      levels in patients with type 2 diabetes. Metformin, independent of exercise,
      significantly increased total plasma GLP-1 and GIP concentrations in these
      patients.

PMID- 24321718
TI  - Increasing diabetes educators' confidence in physical activity and exercise
      counselling: the effectiveness of the "physical activity and exercise toolkit"
      training intervention.
AB  - OBJECTIVE: The objective of this action research was to examine the effectiveness
      of a comprehensive intervention (the toolkit) in improving diabetes educators'
      (DEs') perceptions of their abilities and their patients' abilities related to
      physical activity as part of regular diabetes self-management. METHODS: Two
      separate studies were conducted. Participants completed measures assessing
      confidence, attitudes and perceived difficulty. In study 1, a quasi-experimental
      design was used to examine the impact of the training intervention at 6 months.
      Cross-sectional sampling at baseline and 12 months then was used to assess the
      longer-term impact of the intervention. In study 2, a pre-post design was used to
      test the impact of the intervention at 12-months in a separate sample. RESULTS:
      The primary finding was a consistent increase in DEs' confidence in their ability
      to provide physical activity and exercise counselling with increases of up to 20%
      after the training intervention. Furthermore, DEs reported greater knowledge
      about physical activity (p<0.03) yet perceived physical activity counselling to
      be more difficult after receiving the training (p<0.05). In study 2, the DEs
      reported increases in perceived patient knowledge and confidence in their
      patients (p<0.03) after the intervention. Secondary analyses showed that
      frequently referring to the toolkit was associated with higher counselling
      efficacy and lower perceived difficulty (p<0.03). CONCLUSIONS: These findings
      suggest that the toolkit is an effective resource to improve DEs' confidence in
      the area of physical activity counselling. As a result of this work, the toolkit
      has been adopted as standard diabetes care across Nova Scotia and as a
      foundational resource for DEs across Canada.

PMID- 24321719
TI  - Predicting aerobic fitness improvements after participation in a hybrid
      supervised and home-based exercise program in people with type 2 diabetes.
AB  - OBJECTIVE: Structured, gym-based exercise training has been shown to be effective
      at improving aerobic fitness and glycemic control in persons with type 2
      diabetes. However, community-based diabetes programs more commonly incorporate
      less structured programming, promoting exercise at home. The objectives of this
      study were to evaluate a community-based, hybrid exercise program encouraging
      home-based exercise for improving aerobic fitness, and to examine the components
      of exercise prescription that contribute to this fitness change. METHODS: A
      retrospective analysis of 583 persons with type 2 diabetes who had participated
      in the Toronto Rehabilitation Institute's diabetes exercise program was
      performed. All subjects completed 6 months of structured aerobic and resistance
      exercise supervised once per week on-site, with 4 more unsupervised sessions per
      week completed at home. Cardiopulmonary fitness testing and anthropometric
      measures were performed at baseline and at program completion. A multivariate
      regression analysis examined the outcome of aerobic fitness (peak oxygen
      consumption), controlling for age, sex, body mass index, weight change, initial
      fitness at entry into the program and walking exercise performed (distance,
      duration and pace). RESULTS: Peak oxygen consumption improved significantly from
      19.1+/-0.2 at baseline to 21.9+/-0.3 mL.kg(-1).min(-1) at 6 months (p<0.001).
      Weight and body mass index also improved significantly (p<0.001). The regression
      model was able to predict 76.9% of the variance in aerobic fitness, with distance
      walked contributing the most to improved exercise capacity. CONCLUSIONS: A 6
      month hybrid exercise program delivered in a community rehabilitation program
      setting successfully improved aerobic fitness in people living with type 2
      diabetes.

PMID- 24321720
TI  - Use patterns of antidiabetic regimens by patients with type 2 diabetes.
AB  - OBJECTIVE: To describe the use patterns of metformin-based antidiabetic regimens
      in patients with type 2 diabetes and to identify predictors of initiating
      metformin monotherapy. METHODS: By using administrative databases from Alberta,
      Canada, we identified all metformin users ages 65 years and older between 1998
      and 2010. Rates of metformin use, either alone or in combination with other
      antidiabetic drugs, were evaluated at 6-month intervals. All rates were direct
      age- and sex-standardized using the 2006 Alberta census. Trends over time were
      assessed using Joinpoint regression software (National Cancer Institute, USA). In
      addition, a cohort of new users of antidiabetic drugs was identified and
      multivariable logistic regression models were constructed to identify independent
      predictors of receiving initial treatment with metformin monotherapy. RESULTS:
      Metformin monotherapy became the most common metformin-based regimen (508 of 1000
      persons in 2010). Sulfonylureas were the most prevalent add-on drug to metformin;
      however, their use significantly decreased from 548 of 1000 in 1998 to 182 of
      1000 persons in 2010 (67% reduction; p<0.001), with more patients using newer
      drugs, mainly thiazolidinediones (103 of 1000 persons in 2007). Combination
      therapy of metformin with glinides or insulin also significantly increased during
      the same period. Compared with patients starting sulfonylurea monotherapy,
      patients starting metformin monotherapy were younger, had fewer cardiovascular
      complications and lower healthcare use rates. CONCLUSIONS: In accordance with the
      clinical practice guidelines, patients with type 2 diabetes manage hyperglycemia
      mainly with metformin monotherapy and sulfonylureas are the most common add-on
      therapy. Older age and the presence of nephropathy, liver disease or congestive
      heart failure were important predictors for starting sulfonylurea monotherapy
      rather than metformin monotherapy.

PMID- 24321721
TI  - Oxidative stress-associated neuroretinal dysfunction and nitrosative stress in
      diabetic retinopathy.
AB  - OBJECTIVE: The present study was intended to investigate whether oxidative stress
      is the key regulator to alter neuroretinal biochemical homeostasis and in turn
      aggravate the process of diabetic retinopathy by inducing nitrosative stress in
      the retinal neurovascular unit. METHODS: Peripheral blood mononuclear cell
      reactive oxygen species level was measured by flow cytometry along with
      spectrophotometric detection of malondialdehyde (MDA) and glutamate from serum or
      plasma and a vitreous sample of study groups (i.e. subjects with proliferative
      diabetic retinopathy [PDR], type 2 diabetes without retinopathy [DNR] and healthy
      controls [HCs]). Further, nitrosative stress assessment was performed by
      spectrophotometric and enzyme-linked immunosorbent assay-based detection of serum
      and vitreous nitrite and nitrotyrosine concentrations, respectively. RESULTS: The
      plasma glutamate level remains insignificant between subjects with PDR and DNR
      (p=0.505) or in HC (p=0.1344) individuals. However, serum MDA (p=0.0004), nitrite
      (p=0.0147) and nitrotyrosine (p=0.0129) were found to be strikingly higher among
      PDR subjects compared with the DNR group. Significantly increased levels of
      peripheral blood mononuclear cell reactive oxygen species (p<0.0001), vitreous
      glutamate (p=0.0009, p<0.0001), MDA (p=0.0058, p=0.0003), nitrite (p=0.0014,
      p<0.0001) and nitrotyrosine (p=0.0008, p<0.0001) were found in PDR subjects
      compared with DNR and HC subjects, respectively. CONCLUSIONS: Our observation
      suggests that oxidative stress is associated with impairment in neuroretinal
      biochemical homeostasis among PDR subjects, which further augments retinal
      nitrosative stress and thus worsens the pathogenic process of retinopathy among
      PDR subjects.

PMID- 24321722
TI  - Psychological correlates of eating disorder symptoms and body image in
      adolescents with type 1 diabetes.
AB  - OBJECTIVE: To examine eating disorder symptoms and body image in adolescents with
      type 1 diabetes and to investigate the associations among social support, self
      esteem, health locus of control, eating disorder symptoms and body image.
      METHODS: Forty-six adolescents with type 1 diabetes and 27 healthy comparison
      adolescents completed questionnaires. RESULTS: No significant differences were
      identified in eating disorder symptoms and body image between adolescents with
      type 1 diabetes and healthy comparison adolescents. Regression analyses were
      completed with the full sample of adolescents with type 1 diabetes and healthy
      comparison adolescents. Higher levels of social support and being male were
      associated with a more positive body image, less body dissatisfaction and a lower
      drive for thinness. A belief by the adolescents that parents or healthcare
      providers (i.e. external powerful others locus of control) were in control of
      their health was associated with a more positive body image and less body
      dissatisfaction. Higher self-esteem was associated with a greater drive for
      thinness and a higher level of body dissatisfaction. CONCLUSIONS: Social support,
      health locus of control and self-esteem appear to be important correlates of
      eating disorder symptoms and body image in adolescents with diabetes and their
      typically developing peers.

PMID- 24321723
TI  - The Prediabetes Detection and Physical Activity Intervention Delivery (PRE-PAID)
      program.
AB  - Inspired by increases in the prevalence and incidence of prediabetes, the Pre
      diabetes Detection and Physical Activity Intervention Delivery Project (PRE-PAID)
      is a multiphasic program that identifies persons at high risk for developing type
      2 diabetes, provides an opportunity for culturally appropriate, community-based
      physical activity and facilitates training of qualified exercise professionals on
      diabetes screening as well as prediabetes-specific training recommendations. This
      article provides an overview of the PRE-PAID project and includes some
      preliminary screening data, as well as lessons learned from the implementation of
      community-based physical activity programs that target specific, high-risk
      ethnicities. Recommendations and special considerations involving physical
      activity that targets persons with prediabetes also are discussed. A total of 691
      individuals have undergone the PRE-PAID risk-identification process, which
      involves a brief questionnaire and point-of-care finger-prick hemoglobin A1C
      testing. The mean hemoglobin A1C level was 6.0+/-0.90% (mean +/- standard
      deviation). Questionnaire scores showed that, on average, the individuals
      screened had 3 to 5 typical risk factors for type 2 diabetes, such as high body
      mass index, waist circumference, physical inactivity or family history of
      diabetes. Community-specific breakdowns of these results also are presented in
      this article. Sharing experiences from the PRE-PAID project can help formulate a
      framework for future prediabetes screening and physical activity interventions
      that are community based, target persons with prediabetes and are culturally
      appropriate. 

PMID- 24321724
TI  - Resistance exercise in type 1 diabetes.
AB  - It is relatively well known that moderate-intensity aerobic exercise increases
      the risk of hypoglycemia in individuals with type 1 diabetes. Conversely, brief
      high-intensity (anaerobic) activity can cause post-exercise hyperglycemia. Recent
      evidence has indicated that including small amounts of anaerobic activity, either
      in the form of short sprints or as resistance exercise (weight lifting), during
      aerobic exercise sessions may decrease the drop in blood glucose levels
      associated with moderate-intensity aerobic exercise. This review discusses the
      recent developments in the area of exercise and type 1 diabetes, with a
      particular focus on the effects of resistance exercise. Practical exercise
      recommendations, as well as suggestions for the future direction of research in
      this area, are also provided. 

PMID- 24321725
TI  - Vigorous intensity exercise for glycemic control in patients with type 1
      diabetes.
AB  - Regular physical activity has substantial health benefits in persons with type 1
      diabetes, including reduced risk of complications and cardiovascular mortality as
      well as improved self-rated quality of life. Despite these benefits, individuals
      with type 1 diabetes are often less active than their peers without diabetes.
      When factors such as time constraints, work pressure and environmental conditions
      are often cited as barriers to physical activity in the general population, 2
      additional major factors may also explain the low rates of physical activity in
      young people with type 1 diabetes: (1) fear of hypoglycemia both during and after
      (particularly overnight) exercise and (2) a lack of empiric evidence for the
      efficacy of physical activity for achieving optimal glycemic control. A number of
      acute exercise trials recently showed that the inclusion of vigorous intensity
      physical activity in conventional moderate intensity (i.e. walking and light
      cycling) exercise sessions may overcome these barriers. No studies have tested
      the efficacy of high-intensity physical activity on glycemic control (A1C) or
      post-exercise hypoglycemia in a randomized controlled trial. This article
      summarizes the literature related to the role of physical activity for the
      management of blood glucose levels in individuals with type 1 diabetes and
      provides a rationale for the need of a randomized controlled trial examining the
      effects of vigorous-intensity physical activity on blood glucose control. 

PMID- 24321733
TI  - Metabolomics in diabetes.
AB  - Characterization of metabolic changes is key to early detection, treatment, and
      understanding molecular mechanisms of diabetes. Diabetes represents one of the
      most important global health problems. Approximately 90% of diabetics have type 2
      diabetes. Identification of effective screening markers is critical for early
      treatment and intervention that can delay and/or prevent complications associated
      with this chronic disease. Fortunately, metabolomics has introduced new insights
      into the pathology of diabetes as well as to predict disease onset and revealed
      new biomarkers to improve diagnostics in a range of diseases. Small-molecule
      metabolites have an important role in biological systems and represent attractive
      candidates to understand T2D phenotypes. Characteristic patterns of metabolites
      can be revealed that broaden our understanding of T2D disorder. This technique
      driven review aims to demystify the mechanisms of T2D, to provide updates on the
      applications of metabolomics in addressing T2D with a focus on metabolites based
      biomarker discovery. 

PMID- 24321734
TI  - A simplified approach for FSHD molecular testing.
AB  - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by
      complex genetics linked to DNA rearrangements in a polymorphic genomic region of
      tandemly repeated D4Z4 segments. A panel of FSHD biomarkers including contracted
      D4Z4 array repeat combined with the 4qA(159/161/168)PAS haplotype has been
      proposed as molecular signature for defining alleles causally related to FSHD.
      The aim of the present study was to develop a simple approach for FSHD molecular
      testing in order to extend studies related to the applicability of FSHD molecular
      signature in Greek population. METHODS AND RESULTS: The method comprises: (i)
      visual genotyping of the common 4qA and 10qA subtelomeric haplotypes by a
      multiplex assay in a dipstick format. (ii) Detection of 4qA161 haplotype in D4Z4
      contracted alleles by tri-primer PCR. (iii) Detection of PAS SNP in PLAM region
      and G>C SNP in the first proximal D4Z4 unit by tri-primer PCR. The method was
      evaluated by analysing DNA from monoallelic sources representing common 4q and
      10q haplotypes, samples from 3 FSHD families, 36 unrelated probands and 38
      control individuals of Greek origin. CONCLUSIONS: The proposed method could be a
      very useful tool for FSHD testing making it more accessible to clinical
      diagnostic laboratories and the wider FSHD community.

PMID- 24321735
TI  - Case against GP threatens whole system of healthcare.

PMID- 24321736
TI  - Attention-deficit hyperactivity disorder (ADHD) as a pyridoxine-dependent
      condition: urinary diagnostic biomarkers.
AB  - The data obtained in children with different forms of epilepsy allowed us to
      consider epilepsy as an inborn error of pyridoxine (vitamin B6) metabolism
      (Dolina et al., 2012). Mutual interconnections between ADHD and epilepsy indicate
      that such an approach is reasonable for ADHD. To check such an assumption we
      analyzed in ADHD patients the same parameters of pyridoxal phosphate (PLP)
      dependent tryptophan (TRP) degradation, which were analyzed in epileptic
      children. The level of TRP and concentrations of compounds formed or metabolized
      by TRP degradation, the ratios between some of them, and the level of 4-pyridoxic
      acid were HPLC detected in ADHD children and healthy controls. The data obtained,
      including low values of 4PA/TRP, IND/TRP and IND/KYN ratios, have evidenced
      dramatically impaired activity of pyridoxine-dependent enzymes in ADHD patients.
      Ritalin treatment did not change the general pattern of TRP degradation, but
      still created a kind of balance between some of detected metabolites. However,
      the 4PA/TRP, IND/TRP and IND/KYN ratios remained as low as in untreated patients,
      keeping the importance of diagnostic markers. Almost identical parameters of TRP
      degradation in untreated ADHD and epileptic patients allow to assume that inborn
      disorders of vitamin B6 metabolism are the common biochemical background of both
      diseases. The disturbed activity of PLP dependent enzymes apparently forms those
      profound disturbances of neurotransmitter systems, which are inherent in ADHD:
      low concentrations of monoamines and disordered amino acid metabolism. If vitamin
      B6 disorders are the core biochemical disturbances inherent in ADHD, then the
      long-term pyridoxine treatment is pathogenetically based replacement therapy of
      the disease. According to our data, multi-year pyridoxine treatment normalizes
      completely the pattern of ADHD behavior, without causing any serious side
      effects. 

PMID- 24321737
TI  - Biologic agents for rheumatoid arthritis: can we hypothesize new strategies of
      treatment?
AB  - Rheumatoid arthritis is a complex multifactorial disease, whose pathogenesis has
      not been fully elucidated. Biologic agents have revolutionized RA treatment, but
      a significant percentage of patients does not obtain an adequate response to the
      therapy. Most of the biologic agents do better if combined with conventional
      immunosuppressive DMARDs and they show a similar efficacy profile: most of the
      responders achieve the minimum desirable level of response (ACR20) and only few
      patients obtain a worthwhile clinical improvement (ACR70 or better). We need to
      identify new strategies of treatment, able to comply the non satisfied needs of
      RA patients. Taking inspiration from other medical fields, we could hypothesize a
      combined regimen in which biologic agents are administered simultaneously at a
      low or ultra-low dosage, targeting several pathogenetic mechanisms but avoiding
      important side effects. Alternatively it should be useful to identify rapid
      succession regimens in which biologic drugs are taken according to an established
      sequence. Research in this field is obviously not encouraged by pharmaceutical
      industries, but our efforts should be driven in this direction. According to
      these observations, adequate clinical trials should be designed to search for
      appropriate drugs associations and dosages. 

PMID- 24321738
TI  - Altered autonomic inputs as a cause of pancreatic beta-cell amyloid.
AB  - A partial loss of beta-cell mass and beta-cell dysfunction in Type 2 Diabetes
      Mellitus (T2DM) is associated with amyloid deposition but whether it is causal or
      consequential is debated. Although the in vitro polymerization of amylin has been
      studied in detail, the exact trigger for the mechanism in vivo has not been
      identified. One suggestion is that an increased load on beta-cells results in
      inefficient handling of proteins leading to misfolding and aggregation, but this
      hypothesis is faced with certain paradoxes. We suggest an alternative mechanism
      based on the assumption that polymerization is a spontaneous process. The
      concentration of the polypeptide in beta-cell granules is shown to be sufficient
      to allow polymerization. However if the rate of turnover in normal cells is
      greater than the rate of polymerization, amyloid deposition will not be observed.
      If this is true, it follows that amyloid deposition could be a result of
      increased retention time of amylin in the beta-cell granules. In T2D, the
      sympathetic inputs are known to increase which could result in suppression of the
      secretion process. The increase in the retention time due to this suppression can
      allow polymerization. In addition to this in a prediabetic state parasympathetic
      stimulation increases beta-cell proliferation. This reduces the insulin demand
      per cell thereby increasing the mean retention time. Thus a combination of
      contrasting actions of sympathetic and parasympathetic systems could lead to
      increase in the amyloid deposition. We suggest testable predictions of the
      alternative hypotheses and the lines of research needed to test them.

PMID- 24321739
TI  - Delayed culture conversion due to cigarette smoking in active pulmonary
      tuberculosis patients.
AB  - Although many studies have assessed factors affecting culture conversion during
      tuberculosis treatment, few have looked into the effect of tobacco smoking. This
      study included 89 active pulmonary tuberculosis patients with positive sputum
      culture upon presentation and collected information regarding smoking history and
      culture conversion after 60 days of therapy. Current smokers had a higher risk
      (OR 5.6; 95%CI 1.7-18.7) of non-conversion after two months of therapy when
      compared to never and ex-smokers. Cavities on chest X-ray and alcohol abuse were
      shown to confound this association. After adjustment for cavities on the chest X
      ray and alcohol abuse current smoking compared to current non-smoking remained
      significantly associated with culture non-conversion at 60 days of treatment
      (adjusted OR 6.9; 95%CI 1.8-26.7, p = 0.002) with a significant (p = 0.004) trend
      in adjusted OR with the number of cigarettes smoked daily to 11.6 (1.8-73.4)
      among those smoking more than 20 cigarettes per day. In conclusion tobacco
      smoking was found to delay culture conversion during treatment for pulmonary
      tuberculosis in a dose-dependent manner. More research is needed to elucidate the
      effects of smoking on tuberculosis treatment response, and of smoking cessation
      during tuberculosis treatment. 

PMID- 24321740
TI  - CD8 T cell independent immunity after single dose infection-treatment-vaccination
      (ITV) against Plasmodium yoelii.
AB  - Sporozoite vaccination of both humans and rodents elicits potent anti-malarial
      immunity, but the dose of sporozoites and the number of immunizations required
      varies with vaccination approach. Here we examine the immunological basis for
      superior protection afforded from single-dose vaccination with virulent
      sporozoites administered under prophylatic chloroquine-cover, referred to as
      infection-treatment-vaccination (ITV), compared to the well-studied approach of
      administering radiation-attenuated Plasmodium sporozoites (RAS). Earlier rodent
      studies utilizing ITV and RAS vaccination suggested a major role of CD8 T cells
      in reducing liver parasite burden after sporozoite challenge in a BALB/c mouse
      model. Consistent with this, we find that in C57Bl/6 mice ITV elicits
      substantially higher parasite-specific CD8 T cell responses than RAS vaccination
      and enhances immunity against P. yoelii infection. However, we show ITV-induced
      CD8 T cells are not necessary for protection following liver-stage sporozoite or
      blood-stage parasite challenge. Mechanistically, we found protection afforded
      from single-dose ITV is associated with low grade, transient parasitemia shortly
      following cessation of chloroquine treatment and generation of potent antibody
      responses to blood-stage parasites. Collectively, our data show the mechanistic
      basis for enhanced protective immunity against P. yoelli elicited by ITV in
      highly susceptible C57Bl/6 mice is independent of CD8 T cells. These studies may
      be relevant in understanding the potent immunity observed with ITV in humans. 

PMID- 24321741
TI  - Dietary fructose enhances the incidence of precancerous hepatocytes induced by
      administration of diethylnitrosamine in rat.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a risk for hepatocellular
      carcinoma (HCC), but the association between a high-fructose diet and HCC is not
      fully understood. In this study, we investigated whether a high-fructose diet
      affects hepatocarcinogenesis induced by administration of diethylnitrosamine
      (DEN). METHODS: Seven-week-old male Sprague-Dawley rats were fed standard chow
      (controls), a high-fat diet (54% fat), or a high-fructose diet (66% fructose) for
      8 weeks. All rats were given DEN at 50 MUg/L in drinking water during the same
      period. Precancerous hepatocytes were detected by immunostaining of the placental
      form of glutathione-S-transferase (GST-P). The number of GST-P-positive
      hepatocytes was assessed in liver specimens. RESULTS: Serum levels of total
      cholesterol were similar among the three groups, but serum triglyceride, fasting
      blood glucose, and insulin levels were higher in the high-fructose group compared
      to the high-fat group. In contrast, hepatic steatosis was more severe in the high
      fat group compared with the high-fructose and control groups, but the incidence
      of GST-P-positive specimens was significantly higher in the high-fructose group
      compared to the other two groups. The average number of GST-P-positive
      hepatocytes in GST-P positive specimens in the high-fructose group was also
      higher than those in the other two groups. This high prevalence of GST-P-positive
      hepatocytes was accompanied by higher levels of 8-hydroxydeoxyguanosine in serum
      and liver tissue. CONCLUSIONS: These results indicate that dietary fructose,
      rather than dietary fat, increases the incidence of precancerous hepatocytes
      induced by administration of DEN via insulin resistance and oxidative stress in
      rat. Thus, excessive fructose intake may be a potential risk factor for
      hepatocarcinogenesis.

PMID- 24321743
TI  - Retaining Hispanic dietetic undergraduate students through mentoring and
      professional development.

PMID- 24321742
TI  - Soda consumption during ad libitum food intake predicts weight change.
AB  - Soda consumption may contribute to weight gain over time. Objective data were
      used to determine whether soda consumption predicts weight gain or changes in
      glucose regulation over time. Subjects without diabetes (128 men, 75 women; mean
      age 34.3+/-8.9 years; mean body mass index 32.5+/-7.4; mean percentage body fat
      31.6%+/-8.6%) self-selected their food from an ad libitum vending machine system
      for 3 days. Mean daily energy intake was calculated from food weight. Energy
      consumed from soda was recorded as were food choices that were low in fat (<20%
      of calories from fat) or high in simple sugars (>30%). Food choices were
      expressed as percentage of daily energy intake. A subset of 85 subjects had
      measurement of follow-up weights and oral glucose tolerance (57 men, 28 women;
      mean follow-up time=2.5+/-2.1 years, range 6 months to 9.9 years). Energy
      consumed from soda was negatively related to age (r=-0.27, P=0.0001) and choosing
      low-fat foods (r=-0.35, P<0.0001), but positively associated with choosing solid
      foods high in simple sugars (r=0.45, P<0.0001) and overall average daily energy
      intake (r=0.46, P<0.0001). Energy intake from food alone did not differ between
      individuals who did and did not consume beverage calories (P=0.11). Total daily
      energy intake had no relationship with change in weight (P=0.29) or change in
      glucose regulation (P=0.38) over time. However, energy consumed from soda
      correlated with change in weight (r=0.21, P=0.04). This relationship was
      unchanged after adjusting for follow-up time and initial weight. Soda consumption
      is a marker for excess energy consumption and is associated with weight gain. 

PMID- 24321744
TI  - Prenatal buprenorphine exposure decreases neurogenesis in rats.
AB  - Perinatal opioid exposure has a negative effect on neurogenesis and produces
      neurological consequences. However, its mechanisms of action are incompletely
      understood. Buprenorphine, a mixed opioid agonist/antagonist, is an alternative
      medication for managing pregnant opioid addicts. This study provides evidence of
      decreased neurogenesis and depression-like consequences following prenatal
      exposure to buprenorphine and sheds light on mechanisms of action in a rat model
      involving administration of intraperitoneal injection to pregnant rats starting
      from gestation day 7 and lasting for 14 days and a cultured neurosphere model.
      Results of forced swimming test and tail suspension test showed that pups at
      postnatal day 21 had worse parameters of depression-like neurobehaviors,
      independent of gender. Neurobehavioral changes were accompanied by reduction of
      neuronal composition, biochemical parameters of neural stem/progenitor cells,
      brain-derived neurotrophic factor (BDNF) expression, tropomyosin-related kinase
      receptor type B phosphorylation, protein kinase A (PKA) activity, and cAMP
      response element-binding protein phosphorylation. Results of parallel cell
      studies further demonstrated a negative impact of buprenorphine on cultured
      neurospheres, including proliferation, differentiation, BDNF expression and
      signaling, and PKA activity. Taken together, our results suggest that prenatal
      exposure to buprenorphine might result in depression-like phenotypes associated
      with impaired BDNF action and decreased neurogenesis in the developing brain of
      weanlings. 

PMID- 24321745
TI  - Does total body irradiation conditioning improve outcomes of myeloablative human
      leukocyte antigen-identical sibling transplantations for chronic lymphocytic
      leukemia?
AB  - An allogeneic hematopoietic cell transplantation from an HLA-identical donor
      after high-dose (myeloablative) pretransplantation conditioning is an effective
      therapy for some people with chronic lymphocytic leukemia (CLL). Because CLL is a
      highly radiosensitive cancer, we hypothesized that total body irradiation (TBI)
      conditioning regimens may be associated with better outcomes than those without
      TBI. To answer this, we analyzed data from 180 subjects with CLL receiving
      myeloablative doses of TBI (n = 126) or not (n = 54), who received transplants
      from an HLA-identical sibling donor between 1995 and 2007 and reported to the
      Center for International Blood & Marrow Transplant Research. At 5 years,
      treatment-related mortality was 48% (95% confidence interval [CI], 39% to 57%)
      versus 50% (95% CI, 36% to 64%); P = NS. Relapse rates were 17% (95% CI, 11% to
      25%) versus 22% (95% CI, 11% to 35%); P = NS. Five-year progression-free survival
      and overall survival were 34% (95% CI, 26% to 43%) versus 28% (95% CI, 15% to
      42%); P = NS and 42% (95% CI, 33% to 51%) versus 33% (95% CI, 19% to 48%); P =
      NS, respectively. The single most common cause of death in both cohorts was
      recurrent/progressive CLL. No variable tested in the multivariate analysis was
      found to significantly affect these outcomes, including having failed
      fludarabine. Within the limitations of this study, we found no difference in HLA
      identical sibling transplantation outcomes between myeloablative TBI and
      chemotherapy pretransplantation conditioning in persons with CLL.

PMID- 24321746
TI  - Treatment of graft versus host disease with mesenchymal stromal cells: a phase I
      study on 40 adult and pediatric patients.
AB  - This phase I multicenter study was aimed at assessing the feasibility and safety
      of intravenous administration of third party bone marrow-derived mesenchymal
      stromal cells (MSC) expanded in platelet lysate in 40 patients (15 children and
      25 adults), experiencing steroid-resistant grade II to IV graft-versus-host
      disease (GVHD). Patients received a median of 3 MSC infusions after having failed
      conventional immunosuppressive therapy. A median cell dose of 1.5 * 10(6)/kg per
      infusion was administered. No acute toxicity was reported. Overall, 86 adverse
      events and serious adverse events were reported in the study, most of which
      (72.1%) were of infectious nature. Overall response rate, measured at 28 days
      after the last MSC injection, was 67.5%, with 27.5% complete response. The latter
      was significantly more frequent in patients exhibiting grade II GVHD as compared
      with higher grades (61.5% versus 11.1%, P = .002) and was borderline significant
      in children as compared with adults (46.7 versus 16.0%, P = .065). Overall
      survival at 1 and 2 years from the first MSC administration was 50.0% and 38.6%,
      with a median survival time of 1.1 years. In conclusion, MSC can be safely
      administered on top of conventional immunosuppression for steroid resistant GVHD
      treatment. Eudract Number 2008-007869-23, NCT01764100.

PMID- 24321747
TI  - CD34(+)-selected stem cell boost without further conditioning for poor graft
      function after allogeneic stem cell transplantation in patients with
      hematological malignancies.
AB  - We retrospectively analyzed outcomes of a CD34(+)-selected stem cell boost (SCB)
      without prior conditioning in 32 patients (male/22; median age of 54 years;
      range, 20 to 69) with poor graft function, defined as neutrophils <=1.5 x
      10(9)/L, and/or platelets <=30 x 10(9)/L, and/or hemoglobin <=8.5 g/dL). The
      median interval between stem cell transplantation and SCB was 5 months (range, 2
      to 228). The median number of CD34(+) and CD3(+) cells were 3.4 x 10(6)/kg (.96
      to 8.30) and 9 x 10(3)/kg body weight (range, 2 to 70), respectively.
      Hematological improvement was observed in 81% of patients and noted after a
      median of 30 days (range, 14 to 120) after SCB. The recipients of related grafts
      responded faster than recipients of unrelated grafts (20 versus 30 days, P =
      .04). The cumulative incidence of acute (grade II to IV) and chronic graft-versus
      host disease (GVHD) after SCB was 17% and 26%, respectively. Patients with acute
      GVHD received a higher median CD3(+) cell dose. The 2-year probability of overall
      survival was 45%. We suggest that SCB represents an effective approach to improve
      poor graft function post transplantation, but optimal timing of SCB
      administration, anti-infective, and GVHD prophylaxis needs further evaluation.

PMID- 24321748
TI  - Severe mucositis and Clostridium difficile infection in adult autologous stem
      cell recipients: another question of the chicken or the egg?

PMID- 24321749
TI  - The reversed internal magnet of cochlear implant after magnetic resonance
      imaging.
AB  - Cochlear implants (CI) have now become a standard method of treating severe to
      profound hearing loss. Recently, the number of patients with CI has been rapidly
      increasing as the big benefits of CI become more widely known. Magnetic resonance
      imaging (MRI) has also become a routine diagnostic imaging modality, used in the
      diagnosis of common conditions, including stroke, back pain, and headache. We
      report our recent experience with a case in which internal magnet of the cochlear
      implant was reversed after 1.5-T lumbar spine MRI. This complication is managed
      successfully by reversing the orientation of the external magnet in the head
      coil. 

PMID- 24321750
TI  - Cochlear implantation after resection of an intralabyrinthine schwannoma.
AB  - Intralabyrinthine schwannomas are rare tumors of the distal ends of the cochlear
      and vestibular nerve. Their presence can be debilitating secondary to symptoms of
      hearing loss, vertigo, tinnitus, and imbalance. Currently, treatment to restore
      hearing in those who have become profoundly deaf is not attempted. Additionally,
      resection in patients with functioning hearing is rare, as the surgery assures
      deafness. We report the first case demonstrating the feasibility of resection of
      an intralabyrinthine schwannoma with immediate cochlear implantation. This
      technique addresses the patients hearing status by taking into account advancing
      technology, allowing for an improved quality of life. 

PMID- 24321751
TI  - Verruca vulgaris of tympanic membrane treated with topical immunotherapy.
AB  - Verruca vulgaris is a common skin disease caused by human papillomavirus (HPV)
      infection, but it rarely involves the tympanic membrane. The current treatments
      for verruca are usually destructive and irreversible, should not be performed
      universally; the most relevant therapy will be variable subject to disease
      location, severity, and the patient's immune status. In this report, we
      demonstrated a case with verruca vulgaris of tympanic membrane, who had topical
      immunomodulatory agent treatment successfully with well-preserved hearing, and
      who has no any recurrence up to now for 3 years. In clinical, to cure verruca on
      the vulnerable tympanic membrane without hearing sequela is a dilemma, and there
      is no any treatment guideline due to its rarity. Topical immunomodulatory agent
      with high selectivity, showed great competence on this occasion and verified its
      practicability in treating verruca on unapproachable area, or where bearing vital
      functions; the convenient out-patient-based application also ensures good
      compliance. However, it does need longer duration and higher costs than the other
      routine treatment modalities.

PMID- 24321752
TI  - Jak-Stat signaling pathway may play a role in the pathogenesis of cholesteatoma.
AB  - PURPOSE: Jak-Stat signaling pathway is one of the major signal transduction
      cascades which regulates most of the cellular events such as cell proliferation,
      differentiation, cell migration and apoptosis. This study aims to determine the
      activity of Jak-Stat signaling pathway in the pathogenesis of cholesteatoma.
      MATERIALS AND METHODS: Cholesteatoma and skin samples were obtained from 10
      patients who underwent tympanomastoidectomy for chronic otitis media with
      cholesteatoma. Immunohistochemical analysis of cholesteatoma and skin was
      performed using anti-Jak1, anti-Jak2, anti-Jak3, anti-Stat1, anti-Stat2, anti
      Stat3, anti-Stat4 and anti-Stat5 antibodies. The immunoreactivities in
      cholesteatoma and skin were quantified using H-score measurement and statistical
      comparison was performed. RESULTS: Jak1, Jak2, Jak3, Stat1 and Stat3
      immunoreactivities were not detected in cholesteatoma; in contrast to the skin
      (129.8; 226.7; 33.0; 66.4;115.9). In addition, when H-score measurements of
      Stat2, Stat4 and Stat5 immunoreactivities were compared between cholesteatoma
      (172.8; 166.7; 120.0) and skin (400.0; 284.9; 292.0), statistically significant
      differences were found (p<0.0001, p<0.0001, p<0.0001). CONCLUSIONS: A remarkable
      deficiency in the family members of Jak-Stat signaling pathway was demonstrated
      in cholesteatoma. Therefore, perturbations in Jak-Stat signaling pathway may play
      a role in the pathogenesis of cholesteatoma.

PMID- 24321753
TI  - Effect of nimesulide on the growth of human laryngeal squamous cell carcinoma.
AB  - PURPOSE: To investigate the effect of nimesulide on the growth of human laryngeal
      squamous cell carcinoma. MATERIALS AND METHODS: The effect of NIM on Hep-2 cell
      proliferation was measured by the MTT assay. Flow cytometry was used to evaluate
      the cell cycle and apoptosis in Hep-2 cells. A Western blot analysis was used to
      detect changes in the protein expression levels of COX-2, Survivin and
      proliferating cell nuclear antigen (PCNA) in Hep-2 cells. A Hep-2 tumor xenograft
      model was established in nude mice to observe tumor growth. The changes in the
      xenograft tumors were observed after hematoxylin/eosin staining. The expression
      levels of COX-2, Survivin and PCNA proteins and mRNA were measured by
      immunohistochemical analysis and RT-PCR, respectively. RESULTS: NIM had time- and
      dose-dependent inhibitory effect on the proliferation of Hep-2 cells. NIM could
      prevent the progression of the cell cycle. After NIM treatment, COX-2, Survivin
      and PCNA protein levels were reduced in the Hep-2 cells. The volume and weight of
      the xenograft tumors in the NIM treatment group were significantly reduced. The
      NIM treatment group also exhibited significantly reduced expression levels of COX
      2, Survivin and PCNA at both the protein and mRNA levels. CONCLUSIONS: Our
      results suggested that NIM has significant inhibitory effects on the growth of
      Hep-2 cells and xenograft tumors in nude mice. Selective COX-2 inhibitors could
      potentially become part of a comprehensive treatment for laryngeal squamous cell
      carcinoma. Additional research and development will provide new and broader
      prospects for the prevention and treatment of laryngeal squamous cell carcinoma.

PMID- 24321754
TI  - Differences in neuronal damage and gliosis in the hippocampus between young and
      adult gerbils induced by long duration of transient cerebral ischemia.
AB  - Response to cerebral ischemia in young animals was very different from that in
      the adult. The aim of this study was to investigate differences in neuronal death
      and gliosis in the hippocampal CA1 region (CA1) between adult and young gerbils
      following 5 and 15 min of transient cerebral ischemia. Delayed neuronal death
      (DND) of pyramidal cells occurred in the CA1 was similar in all the adult gerbils
      after 5 and 15 min of ischemia: the DND occurred 4 days after ischemia. In the
      young groups, DND of pyramidal cells in the CA1 region occurred 7 and 3 days
      after 5 and 15 min of ischemia, respectively. On the other hand, the activation
      of GFAP-immunoreactive ((+)) astrocytes and Iba-1(+) microglia was different in
      the young groups from the adult groups after ischemia. The change pattern of GFAP
      immunoreactivity in the adult groups was similar in both the adult groups after
      ischemia; in the young groups, the activation of GFAP(+) astrocytes after 5 min
      of ischemia was much delayed than that after 15 min of ischemia. Activated Iba
      1(+) microglia were aggregated in the stratum pyramidale 4 days after ischemia in
      all the adult ischemia-operated groups; in the young groups, activated Iba-1(+)
      microglia were aggregated in the stratum pyramidale 7 days after 5 min of
      ischemia and 3 days after 15 min of ischemia. These observations indicate that
      DND in young animals is very different from the adult according to different
      duration of transient cerebral ischemia and glial activation is very different in
      young animals after different duration of transient ischemia.

PMID- 24321755
TI  - Oxidative balance, homocysteine, and uric acid levels in older patients with Late
      Onset Alzheimer's Disease or Vascular Dementia.
AB  - This study aimed to investigate whether Late Onset Alzheimer's Disease (LOAD) and
      Vascular Dementia (VAD) might be associated with a distinct profile of oxidative
      stress (OxS) peripheral markers. Serum levels of hydroperoxides, homocysteine,
      advanced oxidation protein products, uric acid, thiols, and total and residual
      antioxidant power were assessed in 103 mild cognitive impairment (MCI), 89 LOAD,
      54 VAD patients and 48 Controls. Compared with Controls, a similar oxidative
      unbalance (high hydroperoxides and low residual antioxidant power) was observed
      in MCI, LOAD and, although less pronounced, VAD. Moreover, individuals with
      simultaneously high levels of homocysteine and uric acid, both well-known risk
      factors for cardiovascular disease, had a high probability to be affected by VAD
      (O.R.:10.50; 95% C.I.: 2.33-47.2), but not LOAD (O.R.: 3.0; 95% C.I.:0.86-10.76)
      compared with individuals with normal values. Our data suggest that, although
      they might share a common OxS-related pathogenesis, VAD and LOAD might maintain
      some distinctive features, with a predominance of "vascular component" in VAD
      compared with LOAD. 

PMID- 24321756
TI  - Separation and enrichment of major quinolizidine type alkaloids from Sophora
      alopecuroides using macroporous resins.
AB  - Matrine (MT), oxymatrine (OM) and sophoridine (SP) are three bioactive alkaloids
      in Sophora alopecuroides. In the present study, the chromatographic
      characteristics of six widely used macroporous resins, namely NKA, NKA-9, HPD
      100, HPD-722, HPD-750, and AB-8, respectively, towards the separation and
      enrichment of the three alkaloids from the aqueous extract of S. alopecuroides
      are critically evaluated. The results indicated that AB-8 resin offered the best
      absorption and desorption capacity and its adsorption data fitted best to the
      Freundlich isotherm. Dynamic adsorption and desorption experiments on packed
      columns of AB-8 resin have been investigated for optimization of chromatographic
      parameters. The adsorption of the alkaloids on the resin was best achieved by 5
      bed volume (BV) of sample solution of pH 10 with a flow rate of 2BV/h. The
      desorption of the compounds from the resin was effectively completed by using 5BV
      of 80% ethanol in water at a flow rate of 2BV/h. After one run of adsorption and
      desorption, the contents of MT, OM, and SP were increased from 9.30, 8.39 and
      9.84% to 22.22, 21.44 and 28.02%, the recovery were 69.4, 78.3 and 72.6%,
      respectively. This method would provide useful information to the industrial
      production of the alkaloids from S. alopecuroides. 

PMID- 24321758
TI  - Liquid chromatography and ion trap mass spectrometry for simultaneous and
      multiclass analysis of antimicrobial residues in feed water.
AB  - This work firstly reported the development of liquid chromatography coupled to an
      ion trap mass spectrometer (LC-MS ion trap) for the simultaneous determination of
      nitrofurans (e.g. nitrofurazone (NFZ), nitrofurantoin (NFT), furazolidone (FZD)
      and furaltadone (FTD)), nitroimidazoles (e.g. metronidazole (MNZ), ronidazole
      (RNZ) and dimetridazole (DMZ)) and chloramphenicol (CAP) in feed water. Isotope
      labeled internal standards for the corresponding target analytes were employed to
      prevent matrix effects that might lead to signal suppression/enhancement. High
      performance liquid chromatography (HPLC) analysis was performed on a Prodigy ODS
      3 column, 2.0mm*150mm, 5MUm with a guard cartridge at a flow rate of 0.2mL/min,
      column oven temperature of 40 degrees C, and an injection volume of 10MUL. Solid
      phase extraction (SPE) procedures, factors affecting HPLC separation (e.g. buffer
      pH and concentrations) and mass spectrometry (MS) parameters were optimized.
      After an off-line SPE by the OASIS HLB cartridges (with an enrichment factor of
      400), the eight antimicrobial agents were separated in 18min using a gradient
      elution of acetonitrile in acidified water (pH 5.0). MS detection was by an ion
      trap MS coupled with electrospray ionization (ESI) in tandem mass spectrometry
      mode (MS/MS) using the nebulizer gas at 35psi, drying gas at 9L/min and drying
      temperature of 325 degrees C. Method linearity was good (r(2)=0.979-0.999) with
      acceptable precision (% RSDs=3.4-26.6%) and accuracy (%recovery=88.4-110.1%).
      Very low limits of detection (LOD) and quantitation (LOQ) were achieved in ranges
      of 0.002-0.06MUg/L and 0.005-0.25MUg/L, respectively. The established method is
      successfully employed by the Department of Livestock Development of Thailand for
      the monitoring of the drug residues in feed waterbecause of its convenience,
      reliability and high sensitivity. 

PMID- 24321757
TI  - Molecularly imprinted polymer coupled with dispersive liquid-liquid
      microextraction and injector port silylation: a novel approach for the
      determination of 3-phenoxybenzoic acid in complex biological samples using gas
      chromatography-tandem mass spectrometry.
AB  - A novel analytical approach based on molecularly imprinted solid phase extraction
      (MISPE) coupled with dispersive liquid-liquid microextraction (DLLME), and
      injector port silylation (IPS) has been developed for the selective
      preconcentration, derivatization and analysis of 3-phenoxybenzoic acid (3-PBA)
      using gas chromatography-tandem mass spectrometry (GC-MS/MS) in complex
      biological samples such as rat blood and liver. Factors affecting the synthesis
      of MIP were evaluated and the best monomer and cross-linker were selected based
      on binding affinity studies. Various parameters of MISPE, DLLME and IPS were
      optimized for the selective preconcentration and derivatization of 3-PBA. The
      developed method offers a good linearity over the calibration range of 0.02
      2.5ngmg(-1) and 7.5-2000ngmL(-1) for liver and blood respectively. Under
      optimized conditions, the recovery of 3-PBA in liver and blood samples were found
      to be in the range of 83-91%. The detection limit was found to be 0.0045ngmg(-1)
      and 1.82ngmL(-1) in liver and blood respectively. SRM transition of 271->227 and
      271->197 has been selected as quantifier and qualifier transition for 3-PBA
      derivative. Intra and inter-day precision for five replicates in a day and for
      five, successive days was found to be less than 8%. The method developed was
      successfully applied to real samples, i.e. rat blood and tissue for quantitative
      evaluation of 3-PBA. The analytical approach developed is rapid, economic,
      simple, eco-friendly and possess immense utility for the analysis of analytes
      with polar functional groups in complex biological samples by GC-MS/MS. 

PMID- 24321759
TI  - Efficient conversion of myricetin from Ampelopsis grossedentata extracts and its
      purification by MIP-SPE.
AB  - In this study, we developed an efficient conversion process of dihydromyricetin
      to myricetin from Ampelopsis grossedentata extracts. The content of myricetin
      increased from 2.38% to 85.57%, demonstrating the successful dehydrogenation of
      dihydromyricetin. Molecularly imprinted polymers (MIPs) were prepared by surface
      imprinting method using silica microspheres as the support matrices and myricetin
      as template. The MIPs were applied for the selective adsorption of myricetin. The
      chemical structure of the MIPs was characterized by Fourier transform infrared
      spectroscopy and scanning electron microscopy. Static, dynamic and selective
      adsorption experiments showed that the MIPs exhibited good adsorption ability,
      rather fast template rebinding kinetics, and appreciate selectivity over
      structurally related compounds. Accordingly, the MIPs were applied as the
      selective sorbent in SPE to purify myricetin obtained through dehydrogenation,
      followed by HPLC-UV analysis. The recoveries of myricetin and dihydromyricetin
      were 92.7% and 55.6%, respectively. This study demonstrates the feasibility of
      using the developed MIP-SPE method to purify and enrich myricetin in the natural
      products. 

PMID- 24321760
TI  - Magnetic solid phase extraction of mefenamic acid from biological samples based
      on the formation of mixed hemimicelle aggregates on Fe(3)O(4) nanoparticles prior
      to its HPLC-UV detection.
AB  - A novel and sensitive solid phase extraction method based on the adsorption of
      cetyltrimethylammonium bromide on the surface of Fe3O4 nanoparticles was
      developed for extraction and preconcentration of ultra-trace amounts of mefenamic
      acid in biological fluids. The remarkable properties of Fe3O4 nanoparticles
      including high surface area and strong magnetization were utilized in this SPE
      procedure so that a high enrichment factor (98) and satisfactory extraction
      recoveries (92-99%) were obtained using only 50mg of magnetic adsorbent.
      Furthermore, a fast separation time (about 15min) was achieved for a large sample
      volume (200mL) avoiding time-consuming column-passing process of conventional
      SPE. A comprehensive study on the parameters effecting the extraction recovery
      such of the amount of surfactant, pH value, the amount of Fe3O4 nanoparticles,
      sample volume, desorption conditions and ionic strength were also presented.
      Under the optimum conditions, the method was linear in the 0.2-200ngmL(-1) range
      and good linearity (r(2)>0.9991) was obtained for all calibration curves. The
      limit of detection was 0.097 and 0.087ngmL(-1) in plasma and urine samples,
      respectively. The relative standard deviation (RSD %) for 10 and 50ngmL(-1) of
      the analyte (n=5) were 1.6% and 2.1% in plasma and 1.2% and 1.9% in urine
      samples, respectively. Finally, the method was successfully applied to the
      extraction and preconcentration of mefenamic acid in human plasma and urine
      samples. 

PMID- 24321761
TI  - Investigation of volatile organic metabolites in lung cancer pleural effusions by
      solid-phase microextraction and gas chromatography/mass spectrometry.
AB  - Headspace solid-phase microextraction (HS-SPME) combined with gas
      chromatography/mass spectrometry (GC/MS) method was applied for the investigation
      of low molecular weight volatile organic metabolites (VOMs) in pleural effusion
      samples. Three important HS-SPME experimental parameters that influence
      extraction efficiency (fiber coating, extraction time and temperature of
      sampling) were optimized by a univariate optimization design. The highest
      extraction efficiency was obtained when sampling was performed at 50 degrees C
      for 10min under agitation using a carboxen/polydimethylsiloxane (CAR/PDMS) fiber.
      A total of 36 volatile metabolites belonging to nine distinct chemical classes
      were identified in 40 pleural effusion samples (20 malignant effusions from lung
      cancer patients and 20 benign effusions from inflammatory patients). Ketones,
      alcohols, and benzene derivatives were the main chemical classes for the
      metabolomic profile of malignant effusions. The average peak areas of ketones and
      alcohols were much higher in malignant group compared to benign group. Together
      with phenols, they exhibit significant differences (P<0.05) between the two
      groups. Particularly, the average peak areas of cyclohexanone and 2-ethyl-1
      hexanol in malignant effusions were significantly higher than those in benign
      ones. Furthermore, of the 36 identified metabolites, 5 compounds including
      cyclohexanone and 2-ethyl-1-hexanol were found to be statistically different
      (Student's t-test, P<0.05) between the two groups by statistical analysis based
      on the peak areas of all identified metabolites. Among them, cyclohexanone and 2
      ethyl-1-hexanol might be considered as candidate biomarkers of lung cancer to
      differentiate malignant from benign effusions. The results show that HS-SPME
      GC/MS is a simple, rapid, sensitive and solvent-free method for the determination
      of VOMs in pleural effusion samples. Pleural effusion is a valuable sample source
      for observation of changes in VOMs for differentiation between lung cancer
      patients and inflammatory individuals. 

PMID- 24321762
TI  - Relationship study of partition coefficients between ionic liquid and headspace
      for organic solvents by HS-GC.
AB  - A general study was carried out to investigate the relationship between analytes
      (organic solvents) and matrix medium (ionic liquids, ILs) by headspace gas
      chromatography (HS-GC) in order to provide a guidance to choose a suitable matrix
      medium during the process of experiment. Thirteen ILs contained different cations
      or anions and two kinds of organic solvents (alkylogens and aprotic solvents
      which involved ability of pro-proton) performed different interactions with ILs
      were chosen in this study. The concentrations of analytes in headspace were
      determined by HS-GC and then logK (the logarithm of concentration radio between
      matrix medium and headspace) was calculated respectively. Factors which affect
      logK, such as logPO/W (the logarithm of the octanol/water partition coefficient
      for a solvent) for different cations (including parent nucleus and alkyl chains)
      and anions of ILs, were investigated. The results indicated that the longer alkyl
      chains, the lower polarity of parent nucleus and the higher polarity of anions
      performed the higher headspace efficiency for alkylogens. Meanwhile, the shorter
      alkyl chains and the lower polarity of parent nucleus make the higher headspace
      efficiency for aprotic solvents which involved ability of pro-proton. For both
      kinds of organic solvents, anions of ILs performed little influences to headspace
      efficiency. The relationship between ILs and organic solvents was primarily
      investigated and a helpful guidance was provided for the application of ILs as
      matrix medium to analyze solvents by HS-GC. The model was successfully used to
      determine the organic residual solvents in ketoconanzale to choose a suitable
      ionic liquid during the process of HS-GC. 

PMID- 24321763
TI  - Enrichment and purification of total flavonoids from Flos Populi extracts with
      macroporous resins and evaluation of antioxidant activities in vitro.
AB  - Enrichment and purification of total flavonoids from Flos Populi extracts were
      studied using five macroporous resins. The static tests indicated that NKA-9
      resin was appropriate and its adsorption data were well fitted to the Langmuir
      and Freundlich isotherms. To optimize the separation process, dynamic adsorption
      and desorption tests were carried out. The optimal adsorption parameters were
      initial concentrations in sample solution of 7.64mg/mL, pH of 5.0, sample loading
      amount of 2.3BV, flow rate of 2BV/h, temperature of 25 degrees C. The optimal
      desorption parameters were deionized water and 20% ethanol each 5BV, then 60%
      ethanol of 10 BV, flow rate of 2BV/h. After one run treatment with NKA-9 resin,
      the content of total flavonoids in the product increased from 11.38% to 53.41%,
      and the recovery yield was 82.24%. The results showed that NKA-9 resin revealed a
      good ability to enrichment total flavonoids from Flos Populi, and the method can
      be referenced for the enrichment of total flavonoids from other materials. The
      antioxidant activities of the purified flavonoids were further evaluated in
      vitro. It showed that the DPPH radical scavenging increased from 59.46% to 82.63%
      at different concentrations (0.06-0.14mg/mL). At different concentrations (0.6
      1.4mg/mL), the hydroxyl radical scavenging increased from 35.39% to 74.12%.
      Moreover, the reducing ability and total oxidant capacity appeared to be dose
      dependent of flavonoids. It indicated that the purified flavonoids can be used as
      a source of potential antioxidant. 

PMID- 24321764
TI  - Determination of polybrominated diphenyl ethers and polychlorinated biphenyls in
      fishery and aquaculture products using sequential solid phase extraction and
      large volume injection gas chromatography/tandem mass spectrometry.
AB  - A new method was developed to determine polybrominated diphenyl ethers (PBDEs)
      and polychlorinated biphenyls (PCBs) in fishery and aquaculture products. Samples
      were extracted by an accelerated solvent extraction system and cleaned up by
      sequential solid phase extraction (SPE) including dispersive SPE (D-SPE) and
      tandem SPE. PBDEs and PCBs were analyzed by a large-volume injection gas
      chromatography triple quadrupole mass spectrometry (LVI-GC-QqQ-MS/MS). Good
      linearity (R(2)>=0.9958) was achieved. Method detection limits (MDLs) were 0.16
      3.3pgg(-1) (wet weight, ww) for PBDEs and 0.13-0.97pgg(-1)ww for PCBs. Mean
      recoveries were 60-140% with relative standard deviations (RSDs) of less than 20%
      in weever fish, scallop and shrimp samples spiked at a lower level of 13-31pgg(
      1)ww and a higher level of 50-125pgg(-1)ww. Certified reference materials were
      analyzed with acceptable results. The method reduced solvent consumption,
      analytical time and labor, and is suitable for the routine analysis of PBDEs and
      PCBs in fishery and aquaculture products. 

PMID- 24321765
TI  - Simultaneous determination of beta-lactam antibiotics and beta-lactamase
      inhibitors in bovine milk by ultra performance liquid chromatography-tandem mass
      spectrometry.
AB  - An ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS)
      method has been developed for the simultaneous determination of four beta-lactam
      antibiotics (amoxicillin, ampicillin, cefotaxime, and cefoperazone) and two beta
      lactamase inhibitors (tazobactam, sulbactam) in bovine milk. The analytes were
      extracted with water from bovine milk and purified with Oasis HLB solid phase
      extraction (SPE) cartridges. The analytes were determined in less than 3min by
      UPLC-MS/MS in positive and negative electrospray ionization (ESI) modes,
      separately. The method was linear over the range of 1-100MUg/L for tazobactam,
      sulbactam, ampicillin, and cefoperazone, and 2-100MUg/L for amoxicillin and
      cefotaxime. The recoveries for all six analytes in bovine milk ranged from 82.5
      to 98.3%. The limits of detection and the limits of quantitation were 0.1
      0.2MUg/L and 0.3-0.5MUg/L, respectively. The intra- and inter-day precisions were
      less than 6% for each compound. 

PMID- 24321766
TI  - LiSr4(BO3)3:Ce3+ phosphor as a new material for ESR dosimetry.
AB  - LiSr4(BO3)3:0.01Ce(3+) phosphor was investigated to assess its potential as a
      material for measurements of radiotherapeutic doses with electron spin resonance
      (ESR). The ESR spectrum of the phosphor irradiated with (60)Co features five ESR
      signals. An isochronal annealing experiment has shown that the strongest of these
      signals is associated with the same trap center as the 473 K peak on the TL glow
      curve of this material. The dose-response is linear in the studied range from
      0.89 to 90.30 Gy. Fading of the signal was also investigated.

PMID- 24321767
TI  - Tat transport of a Sec passenger leads to both completely translocated as well as
      membrane-arrested passenger proteins.
AB  - We have studied the membrane transport of the chimeric precursor protein 16/33,
      which is composed of the Tat(1)-specific transport signal of OEC16 and the Sec
      passenger protein OEC33, both subunits of the oxygen-evolving system associated
      with photosystem II. Protein transport experiments performed with isolated pea
      thylakoids show that the 16/33 chimera is transported in a strictly Tat-dependent
      manner into the thylakoid vesicles yielding mature OEC33 (mOEC33) in two
      different topologies. One fraction accumulates in the thylakoid lumen and is thus
      resistant to externally added protease. A second fraction is arrested during
      transport in an N-in/C-out topology within the membrane. Chase experiments
      demonstrate that this membrane-arrested mOEC33 moiety does not represent a
      translocation intermediate but instead an alternative end product of the
      transport process. Transport arrest of mOEC33, which is embedded in the membrane
      with a mildly hydrophobic protein segment, requires more than 26 additional and
      predominantly hydrophilic residues C-terminal of the membrane-embedded segment.
      Furthermore, it is stimulated by mutations which potentially affect the
      conformation of mOEC33 suggesting that at least partial folding of the passenger
      protein is required for complete membrane translocation. 

PMID- 24321768
TI  - GSTpi protects against angiotensin II-induced proliferation and migration of
      vascular smooth muscle cells by preventing signal transducer and activator of
      transcription 3 activation.
AB  - Angiotensin II (Ang II)-elicited excessive proliferation, hypertrophy and
      migration of vascular smooth muscle cells (VSMCs) are vital to the pathogenesis
      of atheroclerosis. Glutathione S-transferase pi (GSTpi) exists extensively in
      various kinds of cells and protects cells against different stresses. However,
      knowledge remains limited about what GSTpi acts in VSMCs. We investigated the
      effect of GSTpi on Ang II-induced VSMC proliferation, hypertrophy and migration
      and its latent mechanism. Overexpression and RNAi experiments demonstrated that
      GSTpi inhibited Ang II-induced proliferation, hypertrophy and migration of VSMCs
      and arrested progression of cell cycle from G0/G1 to S phase.
      Immunoprecipitation, mass spectrometry and confocal microscopy analyses showed
      that GSTpi directly associated with signal transducer and activator of
      transcription 3 (STAT3) to prevent Ang II-triggered binding of Src to STAT3 and
      thus suppressed Ang II-stimulated phosphorylation and nuclear translocation of
      STAT3, as well as cyclin D1 expression. In contrast, GSTpi didn't affect Ang II
      activated extracellular signal-regulated kinase (ERK1/2). GSTpi acts as a
      negative regulator to prevent Ang II-triggered proliferative signaling in VSMCs,
      suggesting that it may protect vessels against the stresses associated with
      atherosclerosis formation. 

PMID- 24321769
TI  - Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and
      embryonic exon-II-containing MBP isoforms.
AB  - The only known structural protein required for formation of myelin, produced by
      oligodendrocytes in the central nervous system, is myelin basic protein (MBP).
      This peripheral membrane protein has different developmentally-regulated
      isoforms, generated by alternative splicing. The isoforms are targeted to
      distinct subcellular locations, which is governed by the presence or absence of
      exon-Il, although their functional expression is often less clear. Here, we
      investigated the role of exon-Il-containing MBP isoforms and their link with cell
      proliferation. Live-cell imaging and FRAP analysis revealed a dynamic
      nucleocytoplasmic translocation of the exon-II-containing postnatal 21.5-kDa MBP
      isoform upon mitogenic modulation. Its nuclear export was blocked upon treatment
      with leptomycin B, an inhibitor of nuclear protein export. Next to the postnatal
      MBP isoforms, embryonic exon-II-containing MBP (e-MBP) is expressed in primary
      (immature) oligodendrocytes. The e-MBP isoform is exclusively present in OLN-93
      cells, a rat-derived oligodendrocyte progenitor cell line, and interestingly,
      also in several non-CNS cell lines. As seen for postnatal MBPs, a similar
      nucleocytoplasmic translocation upon mitogenic modulation was observed for e-MBP.
      Thus, upon serum deprivation, e-MBP was excluded from the nucleus, whereas re
      addition of serum re-established its nuclear localization, with a concomitant
      increase in proliferation. Knockdown of MBP by shRNA confirmed a role for e-MBP
      in OLN-93 proliferation, whereas the absence of e-MBP similarly reduced the
      proliferative capacity of non-CNS cell lines. Thus, exon-Il-containing MBP
      isoforms may regulate cell proliferation via a mechanism that relies on their
      dynamic nuclear import and export, which is not restricted to the oligodendrocyte
      lineage.

PMID- 24321770
TI  - Energy adaptive response during parthanatos is enhanced by PD98059 and involves
      mitochondrial function but not autophagy induction.
AB  - Parthanatos is a programmed necrotic demise characteristic of ATP (adenosine
      triphosphate) consumption due to NAD+ (nicotinamide adenine dinucleotide)
      depletion by poly(ADP-ribose) polymerase 1 (PARP1)-dependent poly(ADP
      ribosyl)ation on target proteins. However, how the bioenergetics is adaptively
      regulated during parthanatos, especially under the condition of macroautophagy
      deficiency, remains poorly characterized. Here, we demonstrated that the
      parthanatic inducer N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggered ATP
      depletion followed by recovery in mouse embryonic fibroblasts (MEFs). Notably,
      Atg5-/- MEFs showed great susceptibility to MNNG with disabled ATP-producing
      capacity. Moreover, the differential energy-adaptive responses in wild-type (WT)
      and Atg5-/- MEFs were unequivocally worsened by inhibition ofAMP-activated
      protein kinase (AMPK), sirtuin 1 (SIRT1), and mitochondrial activity.
      Importantly, Atg5-/- MEFs disclosed diminished SIRT1 and mitochondrial activity
      essential to the energy restoration during parthanatos. Strikingly, however,
      parthanatos cannot be exasperated by bafilomycin A1 and MNNG neither provokes
      microtubule-associated protein 1A/1B-light chain 3 (LC3) lipidation and p62
      elimination, suggesting that parthanatos does not induce autophagic flux.
      Intriguingly, we reported unexpectedly that PD98059, even at low concentration
      insufficient to inhibit MEK, can promote mitochondrial activity and facilitate
      energy-restoring process during parthanatos, without modulating DNA damage
      responses as evidenced by PARP1 activity, p53 expression, and gammaH2AX (H2A
      histone family, member X (H2AX), phosphorylated on Serine 139) induction.
      Therefore, we propose that Atg5 deficiency confers an infirmity to overcome the
      energy crisis during parthanatos and further underscore the deficits in
      mitochondrial quality control, but not incapability of autophagy induction, that
      explain the vulnerability in Atg5-deficient cells. Collectively, our results
      provide a comprehensive energy perspective for an improved treatment to alleviate
      parthanatos-related tissue necrosis and disease progression and also provide a
      future direction for drug development on the basis of PD98059 as an efficacious
      compound against parthanatos.

PMID- 24321771
TI  - Are Orai1 and Orai3 channels more important than calcium influx for cell
      proliferation?
AB  - Transformed and tumoral cells share the characteristic of being able to
      proliferate even when external calcium concentration is very low. We have
      investigated whether Human Embryonic Kidney 293 cells, human hepatoma cell Huh-7
      and HeLa cells were able to proliferate when kept 72h in complete culture medium
      without external calcium. Our data showed that cell proliferation rate was
      similar over a range of external calcium concentration (2MUM to 1.8mM).
      Incubation in the absence of external calcium for 72h had no significant effect
      on endoplasmic reticulum (ER) Ca(2+) contents but resulted in a significant
      decrease in cytosolic free calcium concentration in all 3 cell types. Cell
      proliferation rates were dependent on Orai1 and Orai3 expression levels in HEK293
      and HeLa cells. Silencing Orai1 or Orai3 resulted in a 50% reduction in cell
      proliferation rate. Flow cytometry analysis showed that Orai3 induced a small but
      significant increase in cell number in G2/M phase. RO-3306, a cdk-1 inhibitor,
      induced a 90% arrest in G2/M reversible in less than 15min. Our data showed that
      progression through G2/M phase after release from RO-3306-induced cell cycle
      arrest was slower in both Orai1 and Orai3 knock-downs. Overexpressing Orai1,
      Orai3 and the dominant negative non-permeant mutants E106Q-Orai1 and E81Q-Orai3
      induced a 50% increase in cell proliferation rate in HEK293 cells. Our data
      clearly demonstrated that Orai1 and Orai3 proteins are more important than
      calcium influx to control cell proliferation in some cell lines and that this
      process is probably independent of ICRAC and Iarc. 

PMID- 24321772
TI  - Ketamine-induced antidepressant effects are associated with AMPA receptors
      mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex.
AB  - Ketamine exerts fast acting, robust, and lasting antidepressant effects in a sub
      anesthetic dose, however, the underlying mechanisms are still not fully
      elucidated. Recent studies have suggested that ketamine's antidepressant effects
      are probably attributed to the activation of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors. The present study aimed to observe the
      effects of AMPA receptor modulators on mammalian target of rapamycin (mTOR) and
      brain-derived neurotrophic factor (BDNF) expression during the procedure of
      ketamine exerting antidepressant effects. Therefore, we pretreated rats with
      NBQX, an AMPA receptor antagonist, or CX546, an AMPA receptor agonist, and
      subsequently observed the immobility time during the forced swimming test (FST)
      and the hippocampal and prefrontal cortical levels of mTOR and BDNF. The results
      showed ketamine decreased the immobility time of rats during the FST and
      increased the hippocampal and prefrontal cortical mTOR and BDNF. NBQX
      pretreatment significantly increased the immobility time and decreased the levels
      of mTOR and BDNF when compared with vehicle 1 (DMSO) pretreatment. CX546
      pretreatment significantly decreased the immobility time and increased the levels
      of mTOR and BDNF when compared with vehicle 2 (DMSO+ethanol) pretreatment. Our
      results suggest ketamine-induced antidepressant effects are associated with AMPA
      receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and
      prefrontal cortex. 

PMID- 24321774
TI  - Changes in the perception of mental illness stigma in Germany over the last two
      decades.
AB  - PURPOSE: To examine the evolution of the perception of the stigma attached to
      mental illness in Germany since 1990 up to the present. SUBJECTS AND METHODS:
      Population surveys were conducted in the old German States (former Federal
      Republic of Germany) in 1990, 2001, and 2011. The perception of stigma attached
      to people with mental illness was assessed with the help of Link's perceived
      discrimination and devaluation scale. RESULTS: In the 2011 survey, less mental
      illness stigma was perceived by respondents than in the previous surveys. In the
      eyes of the German public, the devaluation and rejection of people with mental
      illness has substantially decreased since 1990. DISCUSSION: The perception of a
      decline of the stigmatization is in contrast to the development of the German
      public's attitudes towards persons with mental disorders, which remained
      unchanged or even worsened. CONCLUSION: Perceived and personal attitudes towards
      persons with mental illness have developed differently, and it remains to be seen
      whether perceptions of less public stigma will ultimately be followed by improved
      personal attitudes.

PMID- 24321773
TI  - Shared genetic factors influence risk for bipolar disorder and alcohol use
      disorders.
AB  - Bipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity,
      more than 50% of individuals with bipolar disorder also receive a diagnosis of
      AUD in their lifetimes. Although both disorders are heritable, it is unclear if
      the same genetic factors mediate risk for bipolar disorder and AUD. We examined
      733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate
      process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime
      AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an
      anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively
      more common among individuals with bipolar disorder than in their non-bipolar
      relatives. All illnesses were shown to be heritable and bipolar disorder was
      genetically correlated with AUD, nicotine dependence and anxiety disorders. The
      genetic correlation between bipolar and AUD remained when controlling for
      anxiety, suggesting that unique genetic factors influence the risk for comorbid
      bipolar and AUD independent of anxiety. Our findings provide evidence for shared
      genetic effects on bipolar disorder and AUD risk. Demonstrating that common
      genetic factors influence these independent diagnostic constructs could help to
      refine our diagnostic nosology. 

PMID- 24321775
TI  - Clotting factors to treat thrombolysis-related symptomatic intracranial
      hemorrhage in acute ischemic stroke.
AB  - BACKGROUND: Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after
      ischemic stroke therapy with tissue plasminogen activator (tPA). Clotting factor
      administration may be a treatment option. OBJECTIVE: To determine if treatment
      with clotting factors (fresh frozen plasma [FFP] or cryoprecipitate) was
      associated with improved outcomes in sICH. METHODS: We conducted a retrospective
      cohort study within University of Texas at Houston Stroke registry involving
      consecutive patients from February 1, 2007, to June 30, 2011, with tPA-related
      sICH, including cases with subsequent intra-arterial therapy. Outcomes were
      Modified Rankin Scale (mRS) score at discharge, death, and hematoma expansion.
      RESULTS: Of 921 patients treated with tPA, 48 (5.2%) had sICH and 45 met criteria
      for the study. Nineteen patients received clotting factors (42.2%; 18 received
      FFP and 7 received cryoprecipitate), whereas 26 (57.8%) patients received
      conservative management without clotting factors. None of the patients treated
      with clotting factors and only 2 of those who did not receive clotting factors
      had a good outcome, mRS score of 2 or less. All the patients treated with
      clotting factors and most of those not treated were left bedridden or dead (mRS
      score 4-6), 19 (100%) versus 22 (85%). Mortality was 9 (47.4%) versus 9 (34.6%),
      respectively. There was no difference in hematoma expansion between the 2 groups.
      CONCLUSIONS: We found no evidence that treatment for sICH with clotting factors
      has a favorable effect on clinical or radiological outcomes. However, the sample
      was small because of the low frequency of sICH. New treatments are urgently
      needed for this uncommon yet serious condition.

PMID- 24321776
TI  - A ruptured aneurysm arising at the leptomeningeal collateral circulation from the
      extracranial vertebral artery to the posterior inferior cerebellar artery
      associated with bilateral vertebral artery occlusion.
AB  - We report an extremely rare case of a small ruptured aneurysm of the
      leptomeningeal collateral circulation from the vertebral artery (VA) to the
      posterior inferior cerebellar artery (PICA); this aneurysm was associated with
      bilateral VA occlusion. A 72-year-old woman with sudden headache, nausea, and
      subarachnoid hemorrhage (SAH) was admitted to our hospital. On admission, no
      evidence of cerebral signs or cranial nerve palsy was found. Computed tomography
      imaging showed SAH predominantly in the posterior fossa, and digital subtraction
      angiography revealed bilateral VA occlusion and the left VA aneurysm located
      proximal to the VA union. In addition, a small aneurysm was observed at the
      leptomeningeal collateral circulation located between the extracranial left VA
      and the left PICA. The patient underwent radical surgery on the day of the onset
      of the symptoms associated with SAH. However, the VA aneurysm was unruptured and
      surgically trapped. The small aneurysm arising at the leptomeningeal collateral
      circulation was ruptured during the surgery and was electrocoagulated; the
      collateral circulation was preserved, and no neurologic deficits were observed.
      The postoperative course was uneventful. SAH with the occlusion of major vessels
      should be diagnosed with utmost caution to allow preoperative neurologic and
      radiological assessments. 

PMID- 24321777
TI  - Urachal anomalies in children: surgical or conservative treatment?
AB  - OBJECTIVE: To shed light on the current controversy regarding the best treatment
      option for managing urachal anomalies in children. PATIENTS AND METHODS: A
      retrospective follow-up of a case series comprising 13 children who were
      diagnosed with urachal anomalies was performed. All cases were diagnosed between
      2000 and 2011 and followed up at the Pediatric Urology Unit of San Cecilio
      University Hospital in Granada (Spain). Information about the baseline and follow
      up variables was collected from clinical records. RESULTS: Nine of the 13
      patients were symptomatic (6 patients with urachal cysts and 3 patients with
      urachal persistency). Conservative management was originally used in all but one
      case. During follow-up, reinfection appeared in two cases, and these patients
      were treated surgically. Spontaneous resolution was achieved in eight cases
      (61.5%). Two children with persistent urachal cysts are still being followed (4
      and 6 years after the diagnosis), although ultrasound monitoring reveals a
      gradual reduction in the size of the cysts. The median time between diagnosis and
      resolution was 16.5 months. CONCLUSION: With the exception of cases in which
      there is a clear indication for surgery (i.e. reinfection), a conservative
      approach based on regular monitoring may be useful.

PMID- 24321778
TI  - Retroperitoneoscopic left upper moiety heminephroureterectomy for dribbling
      incontinence.
AB  - A 7-year-old girl underwent a prone, retroperitoneoscopic left upper moiety
      heminephroureterectomy for a non-functioning upper moiety associated with a
      dilated, ectopic ureter. The dilated ureter was noted prenatally, but postnatal
      investigations failed to demonstrate the duplex system. The child remained
      asymptomatic until she represented at 6 years of age, with dribbling of urine.
      She went on to have an ultrasound scan, dimercaptosuccinic acid and magnetic
      resonance urogram, which identified a grossly-dilated fluid-filled structure in
      proximity of the left kidney, but failed to demonstrate the small non-functioning
      left upper moiety. A computed tomography urogram was more helpful in establishing
      the diagnosis. Retroperitoneoscopy via three 5-mm ports allowed clear
      visualisation of both the left duplex ureters, as well as the small non
      functioning upper moiety, which had been challenging on the pre-operative
      imaging. The procedure is described in the accompanying video. The child was
      discharged home the following day and has been completely well and dry at 6
      months' follow-up. 

PMID- 24321779
TI  - FOREWORD: The Birth of Redox Regulation.

PMID- 24321780
TI  - IFPA Meeting 2013 Workshop Report III: maternal placental immunological
      interactions, novel determinants of trophoblast cell fate, dual ex vivo perfusion
      of the human placenta.
AB  - Workshops are an important part of the IFPA annual meeting as they allow for
      discussion of specialised topics. At IFPA meeting 2013 there were twelve themed
      workshops, three of which are summarized in this report. These workshops related
      to various aspects of placental biology but collectively covered areas of
      placental function, cell turnover and immunology: 1) immunology; 2) novel
      determinants of placental cell fate; 3) dual perfusion of human placental tissue.

PMID- 24321781
TI  - Review: placental homeobox genes and their role in regulating human fetal growth.
AB  - The regulation of fetal growth is multifactorial and complex. Normal fetal growth
      is determined by the genetically predetermined growth potential and further
      modulated by maternal, fetal, placental, and environmental factors. The placenta
      provides critical transport functions between the maternal and fetal circulations
      during intrauterine development. Formation of this interface is controlled by
      several growth factors, cytokines and transcription factors including homeobox
      genes. This review summarizes our current knowledge regarding homeobox genes in
      the human placenta and their differential expression and functions in human
      idiopathic fetal growth restriction (FGR). The review also describes the research
      strategies that were used for the identification of homeobox genes, their
      expression in FGR, functional role and target genes of homeobox genes in the
      trophoblasts and the hormonal regulators of homeobox gene expression in vitro. A
      better understanding of molecular pathways driven by placental homeobox genes and
      further elucidation of signaling pathways underlying the hormone-mediated
      homeobox gene developmental programs may offer novel strategies of targeted
      therapy for improving feto-placental growth in idiopathic FGR pregnancies. 

PMID- 24321782
TI  - IFPA Meeting 2013 Workshop Report I: diabetes in pregnancy, maternal dyslipidemia
      in pregnancy, oxygen in placental development, stem cells and pregnancy
      pathology.
AB  - Workshops are an important part of the IFPA annual meeting as they allow for
      discussion of specialized topics. At IFPA meeting 2013 there were twelve themed
      workshops, four of which are summarized in this report. These workshops related
      to various aspects of placental biology but collectively covered areas of
      pregnancy pathologies and placental metabolism: 1) diabetes in pregnancy; 2)
      lipids, fatty acids and the placenta; 3) oxygen in placental development and
      pathologies; 4) stem cells and pathologies. 

PMID- 24321783
TI  - Interactive decision-support tool for risk-based radiation therapy plan
      comparison for Hodgkin lymphoma.
AB  - PURPOSE: To present a novel tool that allows quantitative estimation and
      visualization of the risk of various relevant normal tissue endpoints to aid in
      treatment plan comparison and clinical decision making in radiation therapy (RT)
      planning for Hodgkin lymphoma (HL). METHODS AND MATERIALS: A decision-support
      tool for risk-based, individualized treatment plan comparison is presented. The
      tool displays dose-response relationships, derived from published clinical data,
      for a number of relevant side effects and thereby provides direct visualization
      of the trade-off between these endpoints. The Quantitative Analyses of Normal
      Tissue Effects in the Clinic reports were applied, complemented with newer data
      where available. A "relevance score" was assigned to each data source, reflecting
      how relevant the input data are to current RT for HL. RESULTS: The tool is
      applied to visualize the local steepness of dose-response curves to drive the
      reoptimization of a volumetric modulated arc therapy treatment plan for an HL
      patient with head-and-neck involvement. We also use this decision-support tool to
      visualize and quantitatively evaluate the trade-off between a 3-dimensional
      conformal RT plan and a volumetric modulated arc therapy plan for a patient with
      mediastinal HL. CONCLUSION: This multiple-endpoint decision-support tool provides
      quantitative risk estimates to supplement the clinical judgment of the radiation
      oncologist when comparing different RT options.

PMID- 24321784
TI  - Use of bone scan during initial prostate cancer workup, downstream procedures,
      and associated Medicare costs.
AB  - PURPOSE: For patients with a high likelihood of having metastatic disease (high
      risk prostate cancer), bone scan is the standard, guideline-recommended test to
      look for bony metastasis. We quantified the use of bone scans and downstream
      procedures, along with associated costs, in patients with high-risk prostate
      cancer, and their use in low- and intermediate-risk patients for whom these tests
      are not recommended. METHODS AND MATERIALS: Patients in the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate
      cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason
      score, and clinical T stage were used to define D'Amico risk categories. We
      report use of bone scans from the date of diagnosis to the earlier of treatment
      or 6 months. In patients who underwent bone scans, we report use of bone-specific
      x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and
      bone biopsy within 3 months after bone scan. Costs were estimated using 2012
      Medicare reimbursement rates. RESULTS: In all, 31% and 48% of patients with
      apparent low- and intermediate-risk prostate cancer underwent a bone scan; of
      these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone
      biopsies were uncommon. Overall, <1% of low- and intermediate-risk patients were
      found to have metastatic disease. The annual estimated Medicare cost for bone
      scans and downstream procedures was $11,300,000 for low- and intermediate-risk
      patients. For patients with apparent high-risk disease, only 62% received a bone
      scan, of whom 14% were found to have metastasis. CONCLUSIONS: There is overuse of
      bone scans in patients with low- and intermediate-risk prostate cancers, which is
      unlikely to yield clinically actionable information and results in a potential
      Medicare waste. However, there is underuse of bone scans in high-risk patients
      for whom metastasis is likely.

PMID- 24321785
TI  - Quantification of esophageal tumor motion on cine-magnetic resonance imaging.
AB  - PURPOSE: To quantify the movement of esophageal tumors noninvasively on cine
      magnetic resonance imaging (MRI) by use of a semiautomatic method to visualize
      tumor movement directly throughout multiple breathing cycles. METHODS AND
      MATERIALS: Thirty-six patients with esophageal tumors underwent MRI. Tumors were
      located in the upper (8), middle (7), and lower (21) esophagus. Cine-MR images
      were collected in the coronal and sagittal plane during 60 seconds at a rate of 2
      Hz. An adaptive correlation filter was used to automatically track a previously
      marked reference point. Tumor movement was measured in the craniocaudal (CC),
      left-right (LR), and anteroposterior (AP) directions and its relationship along
      the longitudinal axis of the esophagus was investigated. RESULTS: Tumor
      registration within the individual images was typically done at a millisecond
      time scale. The mean (SD) peak-to-peak displacements in the CC, AP, and LR
      directions were 13.3 (5.2) mm, 4.9 (2.5) mm, and 2.7 (1.2) mm, respectively. The
      bandwidth to cover 95% of excursions from the mean position (c95) was also
      calculated to exclude outliers caused by sporadic movements. The mean (SD) c95
      values were 10.1 (3.8) mm, 3.7 (1.9) mm, and 2.0 (0.9) mm in the CC, AP, and LR
      dimensions. The end-exhale phase provided a stable position in the respiratory
      cycle, compared with more variety in the end-inhale phase. Furthermore, lower
      tumors showed more movement than did higher tumors in the CC and AP directions.
      CONCLUSIONS: Intrafraction tumor movement was highly variable between patients.
      Tumor position proved the most stable during the respiratory cycle in the end
      exhale phase. A better understanding of tumor motion makes it possible to
      individualize radiation delivery strategies accordingly. Cine-MRI is a successful
      noninvasive modality to analyze motion for this purpose in the future.

PMID- 24321787
TI  - The juggernaut of respiratory diseases gains momentum.

PMID- 24321786
TI  - Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung
      cancer cells through the promotion of TRAF6 ubiquitination.
AB  - Autophagy contributes to the pathogenesis of cancer, whereas toll-like receptors
      (TLRs) also play an important role in cancer development and immune escape.
      However, little is known about the potential interaction between TLR signaling
      and autophagy in cancer cells. Here we show that autophagy induced by TLR4 or
      TLR3 activation enhances various cytokine productions through promoting TRAF6
      (TNF receptor-associated factor 6, E3 ubiquitin protein ligase) ubiquitination
      and thus facilitates migration and invasion of lung cancer cells. Stimulation of
      TLR4 and TLR3 with lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid
      [poly(I:C)] respectively triggered autophagy in lung cancer cells. This was
      mediated by the adaptor protein, toll-like receptor adaptor molecule 1
      (TICAM1/TRIF), and was required for TLR4- and TLR3-induced increases in the
      production of IL6, CCL2/MCP-1 [chemokine (C-C motif) ligand 2], CCL20/MIP-3alpha
      [chemokine (C-C motif) ligand 20], VEGFA (vascular endothelial growth factor A),
      and MMP2 [matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type
      IV collagenase)]. These cytokines appeared to be necessary for enhanced migration
      and invasion of lung cancer cells upon TLR activation. Remarkably, inhibition of
      autophagy by chemical or genetic approaches blocked TLR4- or TLR3-induced Lys63
      (K63)-linked ubiquitination of TRAF6 that was essential for activation of MAPK
      and NFKB (nuclear factor of kappa light polypeptide gene enhancer in B-cells)
      pathways, both of which were involved in the increased production of the
      cytokines. Collectively, these results identify induction of autophagy by TLR4
      and TLR3 as an important mechanism that drives lung cancer progression, and
      indicate that inhibition of autophagy may be a useful strategy in the treatment
      of lung cancer. 

PMID- 24321788
TI  - Single inhaler as maintenance and reliever therapy--is it SMART?

PMID- 24321789
TI  - GOLD and ABCD--a good start, but now for the evidence?

PMID- 24321790
TI  - Future of fixed-dose longacting beta2-agonist and antimuscarinic combination
      therapy in COPD.

PMID- 24321791
TI  - HIV testing in people with presumptive tuberculosis: time for implementation.

PMID- 24321792
TI  - Respiratory vaccine uptake during pregnancy.

PMID- 24321793
TI  - China wakes up to the crisis of air pollution.

PMID- 24321794
TI  - Tuberculosis vaccine faces setbacks but optimism remains.

PMID- 24321795
TI  - Jobs, junk food, and geography--asthma risks mount up.

PMID- 24321796
TI  - Desert storm: the pulmonary legacies of Afghanistan and Iraq.

PMID- 24321797
TI  - Matthew Peters: an accidental advocate of tobacco control.

PMID- 24321798
TI  - Fears of a new wave of mesothelioma in home renovators?

PMID- 24321799
TI  - Fires and strikes: the politics of power.

PMID- 24321800
TI  - Black night.

PMID- 24321801
TI  - Beclometasone-formoterol as maintenance and reliever treatment in patients with
      asthma: a double-blind, randomised controlled trial.
AB  - BACKGROUND: According to international treatment guidelines, inhaled rapid-acting
      beta2 agonists should be used for the control of symptoms in patients with
      asthma. We compared the efficacy and safety of an extrafine combination inhaler
      containing a corticosteroid (beclometasone) plus a rapid-onset, long-acting beta2
      agonist (formoterol) with a short-acting beta2 agonist (salbutamol) as reliever
      strategies in patients taking beclometasone-formoterol combination as maintenance
      treatment. METHODS: In a double-blind trial undertaken in 183 centres in 14
      European countries over 48 weeks, patients (aged >=18 years) with asthma that was
      not fully controlled, with a forced expiratory volume in 1 s (FEV1) of at least
      60% predicted, had a 2-week run in. During this period, patients were treated
      with a combination of beclometasone 100 MUg and formoterol 6 MUg per one
      inhalation twice daily plus salbutamol 100 MUg as required delivered by use of a
      pressurised metered-dose inhaler. They were then randomly assigned in a 1:1 ratio
      with a computer-generated randomisation list to receive beclometasone 100 MUg
      plus formoterol 6 MUg or salbutamol 100 MUg as reliever in addition to
      maintenance with beclometasone 100 MUg plus formoterol 6 MUg twice daily. Primary
      outcome was the time to first severe exacerbation (admission to hospital or visit
      to emergency department, or use of systemic steroids for >=3 consecutive days).
      Secondary outcomes were number of severe exacerbations (events per 100 patients
      per year), time to and number of mild exacerbations, additional exacerbation
      variables, lung function, symptom scores, and asthma control. Analysis was by
      intention to treat. The study is registered with ClinicalTrials.gov, number
      NCT00861926. FINDINGS: 1714 patients were randomly assigned to the as-needed
      beclometasone-formoterol (n=857) and as-needed salbutamol groups (n=857), and
      1701 were analysed (852 and 849, respectively). 326 severe exacerbations were
      reported by 251 patients during the study, and 99 versus 152 patients had at
      least one exacerbation during the 48 weeks, respectively. Compared with
      beclometasone-formoterol plus salbutamol as needed, beclometasone-formoterol for
      both maintenance and reliever treatment significantly increased the time to first
      exacerbation (209 days vs 134 days) by 75 days, with a 36% reduction in risk
      (hazard ratio 0.64 [95% CI 0.49 to 0.82]; p=0.0005), and the estimated
      probability was 12% and 18%, respectively (p=0.0003). The number of days with
      mild asthma exacerbations was also lower with as-needed beclometasone-formoterol
      than with as-needed salbutamol (56.04 days per patient per year vs 65.11 days per
      patient per year; 0.86 [0.76 to 0.98]; p=0.021). From the run-in period to week
      48, both treatments improved symptoms (mean change -1.59 [-1.94 to -1.25] in the
      as-needed beclometasone-formoterol group vs -1.44 [-1.78 to -1.10] in the as
      needed salbutamol group, difference -0.15 [-0.60 to 0.30]; p=0.507), percentage
      of asthma control days (9.5% [7.3 to 11.8] vs 10.9% [8.7 to 13.1], respectively, 
      1.4 [-4.3 to 1.6]; p=0.359), use of reliever (-0.29 [-0.38 to -0.20] vs -0.27 [
      0.36 to -0.19], respectively, -0.02 [-0.13 to 0.10]; p=0.794), and lung function
      (FEV1, 0.090 [0.060 to 0.120] vs 0.090 [0.060-0.120], respectively, 0.001 [-0.040
      to 0.040]; p=0.969), and were well tolerated (patients with serious adverse
      events, 32 [4%] and 41 [5%], respectively). INTERPRETATION: Our results lend
      support to the use of the combination of a single inhaled corticosteroid plus a
      rapid-onset, long-acting beta2 agonist for maintenance and relief in patients
      with moderate to severe asthma and provide encouraging data for the formulation
      of beclometasone-formoterol for this use. FUNDING: Chiesi Farmaceutici.

PMID- 24321802
TI  - Efficacy and safety of maintenance and reliever combination budesonide-formoterol
      inhaler in patients with asthma at risk of severe exacerbations: a randomised
      controlled trial.
AB  - BACKGROUND: The Single combination budesonide-formoterol inhaler Maintenance And
      Reliever Therapy (SMART) regimen reduces severe asthma exacerbations in patients,
      but whether the high doses of corticosteroid and beta agonist increase the risk
      of adverse effects with both short-term and cumulative exposure is not certain.
      Our aim was to investigate whether the SMART regimen would reduce the risk of
      overuse of beta agonist, reduce the likelihood of patients to seek medical review
      when such episodes occurred, and if any reduction in severe asthma exacerbations
      would be at the cost of a higher burden of systemic corticosteroid. METHODS: In
      this 24-week trial undertaken at four primary health-care practices and one
      hospital in New Zealand, patients (aged 16-65 years) with a recent asthma
      exacerbation were randomly assigned in a 1:1 ratio to the SMART or standard fixed
      dose regimen. Treatment in the SMART group consisted of two actuations of
      budesonide-formoterol (200 MUg and 6 MUg, respectively, per actuation) twice
      daily, delivered through a combination metered dose inhaler (MDI), with one extra
      actuation as needed for relief of symptoms; treatment in the standard group
      consisted of two actuations of budesonide-formoterol (200 MUg and 6 MUg,
      respectively, per actuation) twice daily through a combination MDI with one to
      two actuations of salbutamol (100 MUg per actuation) by MDI as needed for relief
      of symptoms. MDIs were monitored electronically to measure actual use of
      medication. The allocation sequence for randomisation was computer generated,
      with a block size of eight per site. Participants, investigators, and the
      statistician were not masked to group assignment. The primary outcome was the
      proportion of participants with at least one high-use episode of beta agonist
      (more than eight actuations per day of budesonide-formoterol in addition to the
      four maintenance doses in the SMART group or more than 16 actuations per day of
      salbutamol in the standard group). Analysis was by intention to treat. This trial
      is registered with the Australian New Zealand Clinical Trials Registry, number
      ACTRN12610000515099. FINDINGS: 303 patients were randomly assigned to the SMART
      (n=151) or standard group (n=152). No significant difference was noted between
      the SMART and standard groups in the proportion of participants with at least one
      high-use episode of beta agonist (84 [56%] vs 68 [45%], respectively, relative
      risk 1.24 [95% CI 0.99-1.56]; p=0.058). There were fewer days of high use in the
      SMART group (mean 5.1 days [SD 14.3] vs 8.9 days [20.9], relative rate 0.58 [0.39
      0.88]; p=0.01). Of the patients who had at least one high-use episode, those in
      the SMART group had fewer days of high use without medical review (8.5 days
      [17.8] vs 18.3 days [24.8], 0.49 [0.31-0.75]; p=0.001). The SMART regimen
      resulted in higher inhaled corticosteroid exposure (943.5 MUg budesonide per day
      [1502.5] vs 684.3 MUg budesonide per day [390.5], respectively; ratio of means
      1.22 [1.06-1.41]; p=0.006), but reduced oral corticosteroid exposure (77.5 mg
      prednisone [240.5] vs 126.6 mg prednisone [382.1], respectively; p=0.011), with
      no significant difference in composite systemic corticosteroid exposure (793.7 mg
      prednisone equivalent per year [893.1] vs 772.1 mg prednisone equivalent per year
      [1062.7], respectively; 1.03 [0.86-1.22]; p=0.76). Participants in the SMART
      group had fewer severe asthma exacerbations (35 [weighted mean rate per year
      0.53] vs 66 [0.97]; relative rate 0.54 [0.36-0.82]; p=0.004). INTERPRETATION: The
      SMART regimen has a favourable risk-to-benefit profile and can be recommended for
      use in adults at risk of severe asthma exacerbations. FUNDING: Health Research
      Council of New Zealand.

PMID- 24321803
TI  - GOLD 2011 disease severity classification in COPDGene: a prospective cohort
      study.
AB  - BACKGROUND: The 2011 GOLD (Global Strategy for the Diagnosis, Management, and
      Prevention of Chronic Obstructive Pulmonary Disease [COPD]) consensus report uses
      symptoms, exacerbation history, and forced expiratory volume (FEV1)% to
      categorise patients according to disease severity and guide treatment. We aimed
      to assess both the influence of symptom instrument choice on patient category
      assignment and prospective exacerbation risk by category. METHODS: Patients were
      recruited from 21 centres in the USA, as part of the COPDGene study. Eligible
      patients were aged 45-80 years, had smoked for 10 pack-years or more, and had an
      FEV1/forced vital capacity (FVC) <0.7. Categories were defined with the modified
      Medical Research Council (mMRC) dyspnoea scale (score 0-1 vs >=2) and the St
      George's Respiratory Questionnaire (SGRQ; >=25 vs <25 as a surrogate for the COPD
      Assessment Test [CAT] >=10 vs <10) in addition to COPD exacerbations in the
      previous year (<2 vs >= 2), and lung function (FEV1% predicted >=50 vs <50).
      Statistical comparisons were done with k-sample permutation tests. This study
      cohort is registered with ClinicalTrials.gov, number NCT00608764. FINDINGS: 4484
      patients with COPD were included in this analysis. Category assignment using the
      mMRC scale versus SGRQ were similar but not identical. On the basis of the mMRC
      scale, 1507 (33.6%) patients were assigned to category A, 919 (20.5%) to category
      B, 355 (7.9%) to category C, and 1703 (38.0%) to category D; on the basis of the
      SGRQ, 1317 (29.4%) patients were assigned to category A, 1109 (24.7%) to category
      B, 221 (4.9%) to category C, and 1837 (41.0%) to category D (kappa coefficient
      for agreement, 0.77). Significant heterogeneity in prospective exacerbation rates
      (exacerbations/person-years) were seen, especially in the D subcategories,
      depending on the risk factor that determined category assignment (lung function
      only [0.89, 95% CI 0.78-1.00]), previous exacerbation history only [1.34, 1.0
      1.6], or both [1.86, 1.6-2.1; p<0.0001]). INTERPRETATION: The GOLD classification
      emphasises the importance of symptoms and exacerbation risk when assessing COPD
      severity. The choice of symptom measure influences category assignment. The
      relative number of patients with low symptoms and high risk for exacerbations
      (category C) is low. Differences in exacerbation rates for patients in the
      highest risk category D were seen depending on whether risk was based on lung
      function, exacerbation history, or both. FUNDING: National Heart, Lung, and Blood
      Institute, and the COPD Foundation through contributions from AstraZeneca,
      Boehringer Ingelheim, Novartis, and Sepracor.

PMID- 24321804
TI  - Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol
      fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE):
      a randomised, double-blind, parallel group study.
AB  - BACKGROUND: QVA149 is an inhaled fixed-dose combination therapy under development
      for the treatment of chronic obstructive pulmonary disease (COPD). It combines
      indacaterol (a longacting beta2-agonist) with glycopyrronium (a longacting
      muscarinic antagonist) as a dual bronchodilator. We aimed to compare the
      efficacy, safety, and tolerability of QVA149 versus salmeterol-fluticasone (SFC)
      over 26 weeks in patients with moderate-to-severe COPD. METHODS: In this
      multicentre double-blind, double-dummy, parallel-group study, 523 patients (age
      40 years or older, Global Initiative for Chronic Obstructive Lung Disease [GOLD]
      stages II-III, without exacerbations in the previous year) were randomly assigned
      (1:1; via automated, interactive response technology and stratified for smoking
      status) to once-daily QVA149 110/50 MUg or twice-daily SFC 50/500 MUg for 26
      weeks. Efficacy was assessed in the full analysis set (randomised patients who
      received at least one dose of study drug); safety was assessed in all patients
      who received at least one dose of study drug. The primary endpoint was to
      demonstrate the superiority of QVA149 compared with SFC for the standardised area
      under the curve from 0 to 12 h post dose for forced expiratory volume in 1 second
      (FEV1 AUC0-12h) after 26 weeks of treatment. This trial was registered at
      ClinicalTrial.gov, NCT01315249. FINDINGS: Between March 25, 2011, and March 12,
      2012, 259 patients were randomly assigned to receive QVA149 and 264 to receive
      SFC. At week 26, FEV1 AUC0-12h was significantly higher with QVA149 than with SFC
      (treatment difference 0.138 L; 95% CI 0.100-0.176; p<0.0001). Overall incidence
      of adverse events (including COPD exacerbations) was 55.4% (143 of 258) for the
      QVA149 group and 60.2% (159 of 264) for the SFC group. Incidence of serious
      adverse events was similar between treatment groups (QVA149, 13 of 258 [5.0%];
      SFC 14 of 264 [5.3%]); COPD worsening was the most frequent serious adverse event
      (one of 13 [0.4%] and three of 14 [1.1%], respectively). INTERPRETATION: Once
      daily QVA149 provides significant, sustained, and clinically meaningful
      improvements in lung function versus twice-daily SFC, with significant
      symptomatic benefit. These results indicate the potential of dual bronchodilation
      as a treatment option for non-exacerbating symptomatic COPD patients. FUNDING:
      Novartis Pharma AG.

PMID- 24321805
TI  - Obstructive sleep apnoea and cardiovascular disease.
AB  - Obstructive sleep apnoea (OSA) is a common health concern caused by repeated
      episodes of collapse of the upper airway during sleep. The events associated with
      OSA lead to brain arousal, intrathoracic pressure changes, and intermittent
      episodes of hypoxaemia and reoxygenation. These events activate pathways such as
      oxidative stress, sympathetic activation, inflammation, hypercoagulability,
      endothelial dysfunction, and metabolic dysregulation that predispose patients
      with OSA to hypertension and atherosclerosis. OSA is a common cause of systemic
      hypertension and should be suspected in hypertensive individuals, especially
      those with resistant hypertension. In patients with OSA, continuous positive
      airway pressure (CPAP) treatment reduces blood pressure, and its effects are
      related to compliance and baseline blood pressure. Evidence suggests that OSA is
      a risk factor for stroke and heart failure. An association between coronary heart
      disease and OSA seems to be limited to middle-aged men (30-70 years). Cardiac
      rhythm disorders occur in about half of patients with OSA, but their clinical
      relevance is still unknown. The association of OSA with cardiovascular risk is
      mainly based on studies in men, and an association has yet to be established in
      women. Data on older patients is similarly scarce. Currently, there is not enough
      evidence to support treatment with CPAP for primary or secondary prevention of
      cardiovascular disease. 

PMID- 24321806
TI  - Chronic obstructive pulmonary disease and comorbidities.
AB  - Results of epidemiological studies have shown that chronic obstructive pulmonary
      disease (COPD) is frequently associated with comorbidities, the most serious and
      prevalent being cardiovascular disease, lung cancer, osteoporosis, muscle
      weakness, and cachexia. Mechanistically, environmental risk factors such as
      smoking, unhealthy diet, exacerbations, and physical inactivity or inherent
      factors such as genetic background and ageing contribute to this association. No
      convincing evidence has been provided to suggest that treatment of COPD would
      reduce comorbidities, although some indirect indications are available. Clear
      evidence that treatment of comorbidities improves COPD is also lacking, although
      observational studies would suggest such an effect for statins, beta blockers,
      and angiotensin-converting enzyme blockers and receptor antagonists. Large-scale
      prospective studies are needed. Reduction of common risk factors seems to be the
      most powerful approach to reduce comorbidities. Whether reduction of so-called
      spill-over of local inflammation from the lungs or systemic inflammation with
      inhaled or systemic anti-inflammatory drugs, respectively, would also reduce COPD
      related comorbidities is doubtful. 

PMID- 24321807
TI  - Complex airway disease: an approach to assessment and management.
AB  - Research into new treatments for airway disease focuses on severe disease because
      morbidity, mortality, and health-care costs are substantial and the unmet need is
      greatest. One reason why outcomes are poor in these patients could be that the
      clinical expression of disease is heterogeneous and difficult to classify. As a
      result, guideline-based management algorithms fail. Additionally, difficulties
      with disease classification and misconceptions about the relation between
      different aspects of severe airway disease have hindered new drug development. A
      potential solution is to use a new approach to assess severe airway disease,
      which moves the diagnostic focus from categorisation of patients to
      identification and characterisation of the main drivers of disease. This approach
      will help rather than hinder identification of clinically important phenotypes of
      disease and will facilitate the development of new phenotype-specific treatment
      options. 

PMID- 24321808
TI  - Acute respiratory distress syndrome: from TRALI to trials.

PMID- 24321809
TI  - Mechanical ventilation: strategic improvements.

PMID- 24321810
TI  - Non-small-cell lung cancer: promising advances in treatment.

PMID- 24321811
TI  - Obstructive sleep apnoea: new associations and approaches.

PMID- 24321812
TI  - GOLD COPD categories are not fit for purpose in primary care.

PMID- 24321813
TI  - GOLD COPD categories are not fit for purpose in primary care--authors' reply.

PMID- 24321814
TI  - NICE guidance on inhaled mannitol for treatment of cystic fibrosis.

PMID- 24321815
TI  - Asthma: management of severe disease.

PMID- 24321816
TI  - Bronchiectasis: breaking the cycle of inflammation and infection.

PMID- 24321817
TI  - Chronic obstructive pulmonary disease: important advances.

PMID- 24321818
TI  - Drug-resistant tuberculosis: latest advances.

PMID- 24321820
TI  - Optical artefact characterization and correction in volumetric scintillation
      dosimetry.
AB  - The goals of this study were (1) to characterize the optical artefacts affecting
      measurement accuracy in a volumetric liquid scintillator detector, and (2) to
      develop methods to correct for these artefacts. The optical artefacts addressed
      were photon scattering, refraction, camera perspective, vignetting, lens
      distortion, the lens point spread function, stray radiation, and noise in the
      camera. These artefacts were evaluated by theoretical and experimental means, and
      specific correction strategies were developed for each artefact. The
      effectiveness of the correction methods was evaluated by comparing raw and
      corrected images of the scintillation light from proton pencil beams against
      validated Monte Carlo calculations. Blurring due to the lens and refraction at
      the scintillator tank-air interface were found to have the largest effect on the
      measured light distribution, and lens aberrations and vignetting were important
      primarily at the image edges. Photon scatter in the scintillator was not found to
      be a significant source of artefacts. The correction methods effectively
      mitigated the artefacts, increasing the average gamma analysis pass rate from 66%
      to 98% for gamma criteria of 2% dose difference and 2 mm distance to agreement.
      We conclude that optical artefacts cause clinically meaningful errors in the
      measured light distribution, and we have demonstrated effective strategies for
      correcting these optical artefacts. 

PMID- 24321821
TI  - Characterisation and expression of the biomineralising gene Lustrin A during
      shell formation of the European abalone Haliotis tuberculata.
AB  - The molluscan shell is a remarkable product of a highly coordinated
      biomineralisation process, and is composed of calcium carbonate most commonly in
      the form of calcite or aragonite. The exceptional mechanical properties of this
      biomaterial are imparted by the embedded organic matrix which is secreted by the
      underlying mantle tissue. While many shell-matrix proteins have already been
      identified within adult molluscan shell, their presence and role in the early
      developmental stages of larval shell formation are not well understood. In the
      European abalone Haliotis tuberculata, the shell first forms in the early
      trochophore larva and develops into a mineralised protoconch in the veliger.
      Following metamorphosis, the juvenile shell rapidly changes as it becomes
      flattened and develops a more complex crystallographic profile including an
      external granular layer and an internal nacreous layer. Amongst the matrix
      proteins involved in abalone shell formation, Lustrin A is thought to participate
      in the formation of the nacreous layer. Here we have identified a partial cDNA
      coding for the Lustrin A gene in H. tuberculata and have analysed its spatial and
      temporal expression during abalone development. RT-PCR experiments indicate that
      Lustrin A is first expressed in juvenile (post-metamorphosis) stages, suggesting
      that Lustrin A is a component of the juvenile shell, but not of the larval shell.
      We also detect Lustrin A mRNAs in non-nacre forming cells at the distal-most edge
      of the juvenile mantle as well as in the nacre-forming region of the mantle.
      Lustrin A was also expressed in 7-day-old post-larvae, prior to the formation of
      nacre. These results suggest that Lustrin A plays multiple roles in the shell
      forming process and further highlight the dynamic ontogenic nature of molluscan
      shell formation. 

PMID- 24321823
TI  - Objective duplex ultrasound evaluation of the extracranial circulation in
      multiple sclerosis patients undergoing venoplasty of internal jugular vein
      stenoses: a pilot study.
AB  - OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) is a condition
      associated with multiple sclerosis (MS) and manifested by stenoses in the
      extracranial venous circulation. There is a need for an objective non-invasive
      assessment of CCSVI that is able to accurately identify the location of stenoses
      and quantify physiological changes in blood flows following treatment. METHOD: A
      duplex ultrasound method, extracranial duplex ultrasound (ECDU), is described
      where the internal jugular veins (IJVs) and vertebral veins (VVs) were examined
      in the supine and sitting position before and after venoplasty in eight patients
      with clinically diagnosed MS. High-resolution B-mode imaging was used to detect
      obvious stenoses, intra-luminal membranes, valve abnormalities and vein wall
      thickening. ECDU was then used to assess blood flow including reflux. To assess
      obstruction, venous blood volume flows (BVFs) were taken bilaterally from the
      proximal (J1), mid (J2) and distal (J3) segments of the IJVs and the mid cervical
      VVs. To assess cerebral perfusion, bilateral BVF measurements were taken, in the
      supine position only, from the proximal internal carotid arteries (ICA) and mid
      cervical vertebral arteries (VA). The global arterial cerebral blood flow (GACBF)
      was then calculated as the sum of the ICA and VA measurements. RESULTS: Pre
      venography ECDU detected IJV stenoses or obstruction in all patients. Venography
      findings were consistent with those of the pre-treatment ECDU with the exception
      of the detection of bilateral IJV stenoses in two patients diagnosed with
      unilateral IJV stenosis by ECDU. A significant improvement in GACBF was evident
      following venoplasty (p < 0.05). A trend to improvement in the post-treatment
      BVFs of both the IJVs and the mid cervical VVs was also observed. This
      improvement was most marked in the left VVs (p = 0.052) and the J2 segment of
      right IJVs (p < 0.05). CONCLUSION: The ECDU examination described provides a
      reliable objective assessment of IJV and VV stenoses and, with the use of BVFs,
      can quantify the degree of obstruction. These results support the use of ECDU as
      a non-invasive post-operative assessment of the success of venoplasty. The
      ability of ECDU to measure GACBF provides an additional parameter to monitor
      vascular pathophysiology in MS patients. The current findings support the view
      that the early symptomatic benefits observed after venoplasty for stenoses in the
      extracranial venous circulation may be the result of increased cerebral
      perfusion.

PMID- 24321822
TI  - Vestibular receptors contribute to cortical auditory evoked potentials.
AB  - Acoustic sensitivity of the vestibular apparatus is well-established, but the
      contribution of vestibular receptors to the late auditory evoked potentials of
      cortical origin is unknown. Evoked potentials from 500 Hz tone pips were recorded
      using 70 channel EEG at several intensities below and above the vestibular
      acoustic threshold, as determined by vestibular evoked myogenic potentials
      (VEMPs). In healthy subjects both auditory mid- and long-latency auditory evoked
      potentials (AEPs), consisting of Na, Pa, N1 and P2 waves, were observed in the
      sub-threshold conditions. However, in passing through the vestibular threshold,
      systematic changes were observed in the morphology of the potentials and in the
      intensity dependence of their amplitude and latency. These changes were absent in
      a patient without functioning vestibular receptors. In particular, for the
      healthy subjects there was a fronto-central negativity, which appeared at about
      42 ms, referred to as an N42, prior to the AEP N1. Source analysis of both the
      N42 and N1 indicated involvement of cingulate cortex, as well as bilateral
      superior temporal cortex. Our findings are best explained by vestibular receptors
      contributing to what were hitherto considered as purely auditory evoked
      potentials and in addition tentatively identify a new component that appears to
      be primarily of vestibular origin. 

PMID- 24321819
TI  - Setting appropriate boundaries: fate, patterning and competence at the neural
      plate border.
AB  - The neural crest and craniofacial placodes are two distinct progenitor
      populations that arise at the border of the vertebrate neural plate. This border
      region develops through a series of inductive interactions that begins before
      gastrulation and progressively divide embryonic ectoderm into neural and non
      neural regions, followed by the emergence of neural crest and placodal
      progenitors. In this review, we describe how a limited repertoire of inductive
      signals-principally FGFs, Wnts and BMPs-set up domains of transcription factors
      in the border region which establish these progenitor territories by both cross
      inhibitory and cross-autoregulatory interactions. The gradual assembly of
      different cohorts of transcription factors that results from these interactions
      is one mechanism to provide the competence to respond to inductive signals in
      different ways, ultimately generating the neural crest and cranial placodes. 

PMID- 24321824
TI  - Effects of psychological stress on neutrophil phagocytosis and bactericidal
      activity in humans--a meta-analysis.
AB  - Several authors have reviewed the effects of psychological stress on lymphocyte
      activity. However the effect of psychological stress on neutrophil functions has
      not been reviewed. The present meta-analysis summarizes evidence of the effects
      of psychological stress on neutrophil phagocytosis and bactericidal activity
      collated from a MEDLINE search of the English literature. We searched the
      database to identify the relevant studies through April 30, 2013. Eleven studies
      met our inclusion criteria and we divided them into those addressing transient
      acute stress (3 studies, n=74), academic examinations (4 studies n=101) and
      chronic stress/life events (4 studies, n=193). We performed a meta-analysis of
      the data and calculated total standardized mean differences (SMD) to evaluate the
      effects of chronic stress. Transient acute stressors might both enhance and
      decrease these neutrophil functions. Academic examinations tended to elevate
      neutrophil functions. On the other hand, the total SMDs of neutrophil
      phagocytosis and bactericidal activity altered by chronic stress/life events were
      -0.589 (95% CI: -0.908 to -0.270, p<0.05) and -0.547 (95% CI: -0.845 to -0.248,
      p<0.05), respectively, indicating suppressive effects on these neutrophil
      functions. Further systematic review of more pooled studies is warranted to
      confirm that academic examinations might enhance, whereas chronic stress/life
      events might suppress these neutrophil functions. 

PMID- 24321825
TI  - Brain 18F-FDG PET imaging in the differential diagnosis of parkinsonism.
AB  - AIM: The aims in this study were to evaluate the role of brain F-FDG PET imaging
      in differential diagnosis of parkinsonism and to correlate brain metabolism
      findings with patients' clinical findings. METHODS: Brain F-FDG PET images were
      evaluated both visually and quantitatively using the NeuroQ software in 21
      parkinsonism patients in whom final clinical diagnoses were established. RESULTS:
      Final clinical diagnoses were idiopathic Parkinson disease in 7, multisystem
      atrophy (MSA) in 7, progressive supranuclear palsy (PSP) in 4, corticobasal
      degeneration in 2, and Lewy body disease in 1 patient. Asymmetrical cortical
      hypometabolism was observed in most of the patients in frontal and
      parietotemporal regions. Fifteen of 21 patients had basal ganglia involvement,
      which was bilateral in patients with MSA and more frequently unilateral in
      patients with idiopathic Parkinson disease and PSP. Four patients with PSP and 1
      patient with corticobasal degeneration had thalamic hypometabolism. Cerebellar
      hypometabolism was observed in 4 patients with MSA. The Unified Parkinson Disease
      Rating Scale motor and bradykinesia scores were higher in patients with basal
      ganglia involvement. CONCLUSIONS: Brain F-FDG PET findings in subcortical nuclei
      and cerebellum were found to be useful in differential diagnosis of patients with
      parkinsonism. The extent of cerebral cortical and basal ganglia hypometabolism
      showed correlation with the presentation and severity of clinical findings.

PMID- 24321826
TI  - Lipoma arborescens successfully treated with (90)Y synovectomy.
AB  - Lipoma arborescens (LA) in the knee is a benign intra-articular lipomatous
      proliferation of the synovial membrane, and data on treatment of LA by
      radionuclide therapy is sparse. We present a rare case of bilateral LA in the
      knees successfully treated with injection of Y-citrate colloid. We assessed the
      biodistribution of the radiopharmaceutical through the use of SPECT/CT imaging.
      Our images show slight redistribution of the radiocolloid in the knee joint,
      whereas most of the radioactivity remains localized around the LA. MRI scans
      confirmed the efficacy of this treatment, with a significant reduction in LA
      volume after 6 months. 

PMID- 24321827
TI  - MRI and FDG PET/CT findings in 3 cases of spinal infectious arachnoiditis.
AB  - Spinal arachnoiditis is a disease characterized by inflammation and scarring of
      the arachnoid membrane of the spinal cord. FDG PET/CT findings of spinal
      arachnoiditis have been rarely reported. We present 3 cases of spinal infectious
      arachnoiditis (1 pyogenic and 2 tuberculous). MRI was performed in these 3 cases
      showing thickened spinal meninges with marked enhancement. FDG PET/CT was
      performed in 2 cases showing intense linear FDG uptake along the spinal canal.
      The combination of MRI and FDG PET/CT may be helpful in identifying the
      infectious sites and evaluating the activity of the infection. 

PMID- 24321828
TI  - Metastatic renal cell carcinoma avid for 82Rb but not 18F-FDG.
AB  - Renal cell carcinoma has a variable uptake of F-FDG resulting in poor sensitivity
      and limited clinical application. There is intense interest in improved molecular
      imaging of this condition. We present a case of a 64-year-old man with known
      metastatic renal cell carcinoma found to have intense uptake of Rb but not F-FDG
      in multiple thoracic metastases seen on imaging performed to assess myocardial
      hibernation. 

PMID- 24321829
TI  - Potential role of FDG PET/CT in evaluating patients with hepatic incidentalomas.
AB  - This review article is focused on the role of FDG PET/CT in diagnosing and
      characterizing hepatic incidentalomas. A large variety of unsuspected lesions can
      be detected in the liver both with ultrasound and CT performed for other reasons;
      the prevalence of liver incidentalomas increases in patients with chronic liver
      disease or preexisting oncologic history. The major challenge is to discriminate
      benign from malignant lesions. There is a large body of literature indicating
      that FDG PET/CT is a useful tool to this purpose even if it is unspecific (ie, it
      cannot differentiate a primary tumor from a secondary lesion). Occasionally, FDG
      PET/CT can be useful for biopsy guidance. 

PMID- 24321830
TI  - Inadvertent intra-arterial injection of (123)I-MIBG in a patient with metastatic
      pheochromocytoma.
AB  - We present an interesting image of the inadvertent arterial injection of I-MIBG
      (metaiodobenzylguanidine) in a 36-year-old man with hereditary, metastatic
      pheochromocytoma, who underwent a diagnostic whole-body scan for the evaluation
      of extent of disease before possible I-MIBG therapy. During the tracer injection
      in the left antecubital area, the patient experienced tingling and skin redness
      in the left forearm and hand. 

PMID- 24321831
TI  - Quantitative PET factors predictive of the response to therapy in solid tumors:
      which is the best?

PMID- 24321832
TI  - Synthesis and evaluation of the antiparasitic activity of bis-(arylmethylidene)
      cycloalkanones.
AB  - A series of bis-(arylmethylidene)-cycloalkanones was synthesized by cross-aldol
      condensation. The activity of the compounds was evaluated against amastigotes
      forms of Trypanosoma cruzi and promastigotes forms of Leishmania amazonensis. The
      cytotoxicity of the active compounds on uninfected fibroblasts or macrophages was
      established in vitro to evaluate the selectivity of their antiparasitic effects.
      Six compounds displayed trypanocidal activity against amastigotes intracellular
      forms of T. cruzi with IC50 values ranging from 7.0 to 249 MUM. Besides these six
      compounds, eight other molecules exhibited significant leishmanicidal activity
      (IC50 values ranging from 0.6 to 110.4 MUM). Two compounds can be considered as
      promising antiparasitic lead molecules because they showed IC50 values in the low
      micromolar range (<=1.2 MUM) with an adequate SI (>=19.9). To understand the
      mechanism of action of these compounds, two possible molecular targets were
      investigated: trypanothione reductase (TR) and cruzain.

PMID- 24321833
TI  - A novel tamoxifen derivative, ridaifen-F, is a nonpeptidic small-molecule
      proteasome inhibitor.
AB  - In a survey of nonpeptide noncovalent inhibitors of the human 20S proteasome, we
      found that a novel tamoxifen derivative, RID-F (compound 6), inhibits all three
      protease activities of the proteasome at submicromolar levels. Structure-activity
      relationship studies revealed that a RID-F analog (RID-F-S*4, compound 25) is the
      smallest derivative compound capable of inhibiting proteasome activity, with a
      potency similar to that of RID-F. Kinetic analyses of the inhibition mode and
      competition experiments involving biotin-belactosin A (a proteasome inhibitor)
      binding indicated that the RID-F derivatives interact with the protease subunits
      in a different manner. Culturing of human cells with these compounds resulted in
      accumulation of ubiquitinated proteins and induction of apoptosis. Thus, the RID
      F derivatives may be useful lead chemicals for the generation of a new class of
      proteasome inhibitors. 

PMID- 24321834
TI  - Synthesis of novel pyrano[3,2-f]quinoline, phenanthroline derivatives and studies
      of their interactions with proteins: an application in mammalian cell imaging.
AB  - A series of tri-cyclic pyrano[3,2-f]quinoline and phenanthroline derivatives have
      been synthesized by a HCl-mediated 6-'endo-trig' Michael type ring closure
      reaction of 6-amino-5-(3-hydroxy-3-methylbut-1-ynyl)-2H-chromen-2-one in
      excellent yields. The process is very simple, facile and inexpensive and can
      provide a diverse range of substituted quinoline derivatives from simple and
      easily available starting materials. Moreover, the synthesized derivatives
      exhibit staining property to the cultured HeLa cells after fixing and can be used
      as fluorophores which can bind with protein molecule. 

PMID- 24321835
TI  - Synthesis and biological evaluation of novel substituted 1,3,4-thiadiazole and
      2,6-di aryl substituted imidazo [2,1-b] [1,3,4] thiadiazole derivatives.
AB  - A new series of N-[5-(4-(alkyl/aryl)-3-nitro-phenyl)-[1,3,4-thiadiazol-2-yl]-2,2
      dimethyl-propionamide 4 (a-l) and 6-(4-Methoxy-phenyl)-2-(4-alkyl/aryl)-3-nitro
      phenyl)-Imidazo [2,1-b] [1,3,4] thiadiazole 6 (a-l) were synthesized starting
      from 5-(4-Fluoro-3-nitro-phenyl)-[1,3,4] thiadiazole-2-ylamine. The synthesized
      compounds were characterized by IR, NMR, mass spectral and elemental analysis.
      All the compounds were tested for antibacterial and antifungal activities. The
      antimicrobial activities of the compounds were assessed by well plate method
      (zone of inhibition). Compounds 4a, 4c and 6e, 6g displayed appreciable activity
      at the concentration 0.5-1.0 mg/mL.

PMID- 24321836
TI  - The impact of job stressors on health-related quality of life of nursing
      assistants in long-term care settings.
AB  - This study aimed to investigate the relationship between various job stressors
      and health-related quality of life among female nursing assistants working in
      long-term care facilities. A cross-sectional study was conducted in Taiwan. Data
      were collected using a structured, well-designed, pre-tested questionnaire with
      background questions and questions about job stressors and health-related quality
      of life as measured by SF-12. Our empirical results show that nursing assistants
      with higher scores for job control and work-related social support tend to enjoy
      better mental health, as indicated by higher mental component summary scores.
      Additionally, nursing assistants with higher psychological demand scores tend to
      have worse overall health, as indicated by lower physical component summary and
      mental component summary scores. We suggest reducing selected job stressors and
      enhancing job control to improve nursing assistants' health-related quality of
      life. 

PMID- 24321838
TI  - Medical error and disclosure - a view from the U.K.
AB  - Whilst the steps for reacting to and communicating following a surgical error
      should be clear to all, actual practice is punctuated by a range of failures
      which lead to the harm done by the error being compounded by inadequacies in the
      disclosure and subsequent processes. This article outlines best practice at the
      current time within the United Kingdom when responding to a surgical error and it
      also reports the type of behaviours which result in poor levels of satisfaction
      from the patients' perspective - often resulting in litigation being invoked. 

PMID- 24321837
TI  - Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety
      like behavior: involvement of 5HT1A receptors and previous stressful experience.
AB  - The prelimbic medial prefrontal cortex (PL) is an important encephalic structure
      involved in the expression of emotional states. In a previous study, intra-PL
      injection of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present
      in the Cannabis sativa plant, reduced the expression of fear conditioning
      response. Although its mechanism remains unclear, CBD can facilitate 5HT1A
      receptor-mediated neurotransmission when injected into several brain structures.
      This study was aimed at verifying if intra-PL CBD could also induce anxiolytic
      like effect in a conceptually distinct animal model, the elevated plus maze
      (EPM). We also verified if CBD effects in the EPM and contextual fear
      conditioning test (CFC) depend on 5HT1A receptors and previous stressful
      experience. CBD induced opposite effects in the CFC and EPM, being anxiolytic and
      anxiogenic, respectively. Both responses were prevented by WAY100,635, a 5HT1A
      receptor antagonist. In animals that had been previously (24h) submitted to a
      stressful event (2h-restraint) CBD caused an anxiolytic, rather than anxiogenic,
      effect in the EPM. This anxiolytic response was abolished by previous injection
      of metyrapone, a glucocorticoid synthesis blocker. Moreover, restraint stress
      increased 5HT1A receptors expression in the dorsal raphe nucleus, an effect that
      was attenuated by injection of metyrapone before the restraint procedure. Taken
      together, these results suggest that CBD modulation of anxiety in the PL depend
      on 5HT1A-mediated neurotransmission and previous stressful experience. 

PMID- 24321839
TI  - Totally extraperitoneal laparoscopic hernioplasty versus open extraperitoneal
      approach for inguinal hernia repair: a meta-analysis of outcomes of our current
      knowledge.
AB  - BACKGROUND: The aim of this article is to explore the clinical effects between
      open extraperitoneal approaches and totally extraperitoneal laparoscopic
      hernioplasty (TEP) in the repair of inguinal hernias. METHODS: The electronic
      databases Pubmed, Medline, Embase, Web of science and the Cochrane Library were
      used to search for articles from January 1992 to March 2013. The present meta
      analysis pooled the effects of outcomes of a total of 1157 patients with 1377
      hernias enrolled into 10 randomized controlled trials and 2 comparative studies.
      The data was analyzed using the statistic software Stata12.0 and IBM SPSS
      Statistics 19. RESULTS: Significant advantages of totally extraperitoneal
      laparoscopic hernioplasty (TEP) compared to the open extraperitoneal approach
      include a lower incidence of total postoperative complications (Odds Ratio,
      0.544; 95% confidence interval, 0.369-0.803), a reduction in urinary problems
      (0.206[0.064,0.665]), an earlier return to normal activities or work (SMD = 
      1.798[-3.322,-0.275]), and a shorter length of hospital stay (-1.995 [-2.358,
      1.632]). No difference was found in operative time, the incidence of hernia
      recurrence, chronic pain, intraoperative complications, seromas or hematomas,
      wound infection and testicular problems between the two techniques. One
      significant advantage for the open extraperitoneal inguinal hernia repair was a
      lower incidence of peritoneal tears (46.504 [15.399,140.437]). CONCLUSIONS:
      Totally extraperitoneal laparoscopic hernioplasty (TEP) and open extraperitoneal
      mesh repair are equivalent in most of the analyzed outcomes. TEP is associated
      with shorter hospital stay, quicker return to normal activities or work, lower
      incidence of total postoperative complications and urinary problems, while the
      open extraperitoneal method has less incidence of peritoneal tears.

PMID- 24321840
TI  - Male sex and vascular risk factors affect cystatin C-derived renal function in
      older people without diabetes or overt vascular disease.
AB  - BACKGROUND/OBJECTIVES: to explore the effect of ageing on renal function with
      cystatin C as the marker of glomerular filtration rate (GFR) in the general
      population without vascular disease or diabetes. DESIGN: a cross-sectional
      analysis of a healthy subset from the Good Aging in Skane-cohort study
      representative of the Swedish general population. SUBJECTS: 1252 participants
      without vascular disease and diabetes (43.9% men) of whom 203 were over 80 years
      old were included from the original cohort of 2931. METHODS: plasma cystatin C
      and plasma creatinine were used as markers for GFR. Estimated GFR (eGFR) was
      calculated with three chronic kidney disease epidemiology collaboration (CKD-EPI)
      formulas involving cystatin C, creatinine or both. RESULTS: the median for plasma
      cystatin C was 0.93 mg/l (60-69 years old), 1.04 (70-79 years old) and 1.24 (80+
      years old). The difference in mg/l between the 5th and 95th percentile was 0.46,
      0.62 and 0.90 for these age groups. Male sex increased the age effect on plasma
      cystatin C levels with 0.004 mg/l/year (P = 0.03), adjusted for vascular risk
      factors. Smoking, lower HDL and higher diastolic blood pressure were associated
      with higher cystatin C levels. 54.7% (CKD-EPI creatinine) to 73.9% (CKD-EPI
      cystatin C) of the 80+ had an eGFR < 60 ml/min/1.73 m2. CONCLUSION: non-diabetics
      without overt vascular disease exhibit an age related but heterogeneous decline
      in renal function. The ageing effect is more pronounced in men. At least half of
      healthy 80+ years old could be expected to have at least CKD Stage 3 with eGFR <
      60 ml/min/1.73 m2.

PMID- 24321841
TI  - Falls prevention in hospitals and mental health units: an extended evaluation of
      the FallSafe quality improvement project.
AB  - BACKGROUND: inpatient falls are a major patient safety issue causing distress,
      injury and death. Systematic review suggests multifactorial assessment and
      intervention can reduce falls by 20-30%, but large-scale studies of
      implementation are few. This paper describes an extended evaluation of the
      FallSafe quality improvement project, which presented key components of
      multifactorial assessment and intervention as a care bundle. METHODS: : data on
      delivery of falls prevention processes were collected at baseline and for 18
      months from nine FallSafe units and nine control units. Data on falls were
      collected from local risk management systems for 24 months, and data on under
      reporting through staff surveys. RESULTS: : in FallSafe units, delivery of seven
      care bundle components significantly improved; most improvements were sustained
      after active project support was withdrawn. Twelve-month moving average of
      reported fall rates showed a consistent downward trend in FallSafe units but not
      controls. Significant reductions in reported fall rate were found in FallSafe
      units (adjusted rate ratio (ARR) 0.75, 95% confidence interval (CI) 0.68-0.84 P <
      0.001) in the 12 months following full implementation but not in control units
      (ARR 0.91, 95% CI 0.81-1.03 P = 0.13). No significant changes in injurious fall
      rate were found in FallSafe units (ARR 0.86, 95% CI 0.71-1.03 P = 0.11), or
      controls (ARR 0.88, 95% CI 0.72-1.08 P = 0.13). In FallSafe units, staff certain
      falls had been reported increased from 60 to 77%. CONCLUSION: : introducing
      evidence-based care bundles of multifactorial assessment and intervention using a
      quality improvement approach resulted in improved delivery of multifactorial
      assessment and intervention and significant reductions in fall rates, but not in
      injurious fall rates.

PMID- 24321842
TI  - Job strain in the public sector and hospital in-patient care use in old age: a 28
      year prospective follow-up.
AB  - BACKGROUND: high job strain increases the risk of health decline, but little is
      known about the specific consequences and long-term effects of job strain on old
      age health. OBJECTIVES: purpose was to investigate whether physical and mental
      job strain in midlife was associated with hospital care use in old age. METHODS:
      study population included 5,625 Finnish public sector employees aged 44-58 years
      who worked in blue- and white-collar professions in 1981. The number of in
      patient hospital care days was collected from the Finnish Hospital Discharge
      Register for the 28-year follow-up period. RESULTS: rates of hospital care days
      per 1,000 person-years for men were 7.78 (95% confidence interval [CI] 7.71-7.84)
      for low, 9.68 (95% CI 9.50-9.74) for intermediate and 12.56 (95% CI 12.47-12.66)
      for high physical job strain in midlife. The corresponding rates for women were
      6.63 (95% CI 6.57-6.68), 7.91 (95% CI 7.87-7.95) and 10.35 (95% CI 10.25-10.42),
      respectively. Rates were parallel but lower for mental job strain. Reporting high
      physical job strain in midlife increased the risk of hospital care in old age
      compared with those who reported low job strain, fully adjusted incidence rate
      ratio 1.17 (95% CI 1.00-1.38) for men and 1.42 (95% CI 1.25-1.61) for women.
      These associations were robust in analyses confined to hospital care that took
      place after the employees had turned 65 years. CONCLUSION: exposure to high
      mental and, particularly, high physical job strain in midlife may set employees
      on a higher healthcare use trajectory which persists into old age.

PMID- 24321843
TI  - The Hachinski ischemic scale and cognition: the influence of ethnicity.
AB  - OBJECTIVE: cardiovascular burden is considered a risk factor for the development
      of cognitive dysfunction and dementia. While this link is well established in the
      literature, implementing this work in primary care settings remains a challenge.
      The goal of this study is to examine the utility of the Hachinski Ischemic Scale
      (HIS) in identifying cognitive dysfunction and diagnosis of mild cognitive
      impairment (MCI) in an ethnically diverse sample. METHODS: data were analysed on
      517 participants (211 Mexican Americans and 306 non-Hispanic Whites) recruited
      from Project FRONTIER, a study of rural health. Neuropsychological measures were
      utilised to assess for cognitive functioning. RESULTS: among non-Hispanic Whites,
      HIS scores were significantly related to poorer performance on tasks of global
      cognition [B (SE) = -0.13 (0.06), P = 0.02], immediate memory [B (SE) = -0.85
      (0.26), P < 0.001], attention [B (SE) = -1.6 (0.36), P < 0.001] and executive
      functioning [B (SE) = 0.46 (0.12), P < 0.001], and significantly predicted
      diagnosis of MCI [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.2-1.6].
      For Mexican Americans, HIS scores were significantly related to immediate memory
      [B (SE) = -0.78 (0.28), P = 0.01], attention [B (SE) = -0.74 (0.36), P = 0.04]
      and executive functioning [B (SE) = 0.37 (0.14), P = 0.01]; however, HIS scores
      were not significantly related to diagnosis of MCI in Mexican Americans (OR =
      1.2, 95% CI = 0.96-1.4, P = 0.116). CONCLUSION: HIS scores were related to
      cognitive functioning; however, these results differed by ethnicity. It is
      possible that these findings indicate that vascular factors may increase risk for
      MCI among non-Hispanic Whites but not for Mexican Americans. These findings are
      consistent with past research that suggests risk factors for MCI may differ by
      ethnicity.

PMID- 24321845
TI  - A new IAEA handbook quantifying the transfer of radionuclides to wildlife for
      assessment tools.

PMID- 24321844
TI  - Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy
      accelerates murine cutaneous wound closure by attenuating pro-inflammatory
      factors and secreting IL-10.
AB  - Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy is under
      consideration for treating peripheral and cardiac ischemia. However, the
      therapeutic efficacy of nanofiber-expanded human umbilical cord blood-derived
      (NEHUCB) CD34+ cell therapy for wound healing and its mechanisms are yet to be
      established. Using an excision wound model in NOD/SCID mice, we show herein that
      NEHUCB-CD34+ cells home to the wound site and significantly accelerate the wound
      healing process compared to vehicle-treated control. Histological analysis
      reveals that accelerated wound closure is associated with the re
      epithelialization and increased angiogenesis. Additionally, NEHUCB-CD34+ cell
      therapy decreases expression of pro-inflammatory cytokines, such as TNF-alpha, IL
      1beta, IL-6 and NOS2A in the wound bed, and concomitantly increases expression of
      IL-10 compared to vehicle-treated control. These findings were recapitulated in
      vitro using primary dermal fibroblasts and NEHUCB-CD34+ cells. Moreover, NEHUCB
      CD34+ cells attenuate NF-kappaB activation and nuclear translocation in dermal
      fibroblasts through enhanced secretion of IL-10, which is known to bind to NF
      kappaB and suppress transcriptional activity. Collectively, these data provide
      novel mechanistic evidence of NEHUCB-CD34+ cell-mediated accelerated wound
      healing.

PMID- 24321846
TI  - A characterization study of resveratrol/sulfobutyl ether-beta-cyclodextrin
      inclusion complex and in vitro anticancer activity.
AB  - A resveratrol/sulfobutylether-beta-cyclodextrin inclusion complex was prepared
      using the freeze-drying method and characterized in solution through UV-vis
      spectroscopy, solubility phase studies and Job's plot methods. At the solid state
      it was characterized using the FTIR-ATR technique. Sulfobutylether-beta
      cyclodextrin has a high affinity for the drug, and forms an inclusion complex
      with a 1:1 molar ratio both in solution and as a solid sample. It also has a high
      stability constant (Kc, 10,114 M(-1)). Complexation strongly increases the water
      solubility of resveratrol (from 0.03 mg/ml to 1.1 mg/ml, at 25  degrees C) and
      positively influences its in vitro anticancer activity which was observed on a
      human breast cancer cell line (MCF-7). In solid phase, FTIR-ATR revealed itself
      as being a useful technique in elucidating the complexation mechanism, which it
      did by emphasizing the functional groups involved in the activation of non
      covalent "host-guest" interactions.

PMID- 24321847
TI  - Synthesis of highly fluorescent gold nanoclusters using egg white proteins.
AB  - Gold nanoclusters (AuNCs) have gained interest during the recent years because of
      their low toxicity and finer size for the bioimaging and biolabeling applications
      in comparison to the semiconductor quantum dot analogues. Diverse materials such
      as sulfur compounds, peptides, dendrimers, proteins, etc., are exploited for the
      preparation of AuNCs. Henceforth, highly fluorescent, water-soluble, and few atom
      containing gold nanoclusters are created using a rapid, straightforward, and
      green method. In this regard for the first time chicken egg white (CEW), one of
      the most unique materials, is utilized in an aqueous solution under basic
      conditions at physiological temperature for the preparation of AuNCs. Tyrosine
      and tryptophan amino acid residues are responsible for the conversion of Au ions
      to Au(0) under alkaline condtions. CEW contains four major proteins of which the
      main constituent protein, ovalbumin also leads to the formation of the AuNCs with
      a higher fluorescence emission compared to the CEW. The ratios between the
      different reaction partners are very crucial, along with temperature and time for
      the preparation of AuNCs with high photoluminescence emission. The limited
      vibrational motion of the proteins under alkaline condition and the bulkiness of
      the proteins help in the formation of AuNCs. 

PMID- 24321848
TI  - Anesthetic technique and acute kidney injury in endovascular abdominal aortic
      aneurysm repair.
AB  - OBJECTIVE: Prior studies suggest that general anesthesia (GA) is associated with
      worse cardiopulmonary outcomes after endovascular abdominal aortic aneurysm
      repair (EVAR). Patients undergoing EVAR are at a high risk of developing
      perioperative acute kidney injury (AKI), and the relationship between anesthetic
      technique and AKI in these patients is not well-characterized. The authors sought
      to determine if anesthetic technique affected the risk of AKI in patients
      undergoing EVAR. DESIGN: Retrospective, observational cohort study analyzed using
      a multivariate logistic regression model to assess the effects of anesthetic
      technique on renal outcome. SETTING: Multiple institutions, mainly in North
      America. PARTICIPANTS: Patients in the American College of Surgeons National
      Surgical Quality Improvement Program from 2005-2010 undergoing EVAR.
      INTERVENTIONS: The authors investigated the association between anesthetic
      techniques, comparing GA to alternative (non-GA) techniques, and AKI.
      MEASUREMENTS AND MAIN RESULTS: AKI was defined as an increase in the creatinine
      level of>2 mg/dL and/or dialysis. Of 13,026 patients, 84.4% underwent GA and
      15.6% underwent non-GA techniques. AKI developed in 2.0% of the GA group and 1.4%
      of the non-GA group (unadjusted odds ratio [OR] 1.43, p = 0.075; adjusted OR
      [aOR] 1.00, p = 0.99). Risk factors for AKI include ASA class, ruptured aneurysm,
      preoperative renal dysfunction, symptomatic cardiovascular disease, and
      perioperative blood transfusion. CONCLUSIONS: Anesthetic technique is not
      independently associated with the risk of AKI in patients undergoing EVAR.

PMID- 24321849
TI  - Mutagenicity of smoke condensates from Canadian cigarettes with different design
      features.
AB  - There is currently limited knowledge regarding the impact of different cigarette
      designs on the toxicological properties of cigarette smoke condensate (CSC). This
      study used the Salmonella Mutagenicity Assay to examine the mutagenic activity of
      mainstream CSCs from 11 commercial Canadian cigarette brands with different
      design features or tobacco blend. The brands were selected to include design
      features that are common for cigarettes sold in the Canadian market, as well as
      cigarettes with alternate filters (charcoal or MicroBlueTM), the super slim
      design, and cigarettes containing mixed blends of different tobacco types. CSCs
      were obtained using the International Organization for Standardization (ISO) and
      Health Canada Intense (HCI) smoking regimes, and mutagenic activity was assessed
      using Salmonella strains TA98, YG1041 and YG5185. Comparisons of the commercial
      brands to the Kentucky 3R4F, the Canadian Monitor 8 reference and a Canadian best
      seller revealed no significant reduction in CSC mutagenicity for cigarettes with
      alternate filters. However, the super slim design did afford some reduction in
      mutagenic potency. Nevertheless, since the study did not attempt to evaluate the
      impact of the cigarette designs on human health at the individual or population
      level, the super slim cigarettes cannot be considered 'reduced-harm' cigarettes. 

PMID- 24321850
TI  - Comparative toxicity of carbaryl, carbofuran, cypermethrin and fenvalerate in
      Metaphire posthuma and Eisenia fetida -a possible mechanism.
AB  - To establish the use of Metaphire posthuma as a sensitive test model for
      ecotoxicological studies, acute toxicity testing of carbaryl, carbofuran,
      cypermethrin and fenvalerate on Eisenia fetida and Metaphire posthuma were
      carried out. Two different types of bioassays, contact filter paper toxicity and
      soil toxicity bioassays were used to determine LC50 values for these
      insecticides. Among the tested chemicals, carbofuran was the most toxic to both
      the earthworm species. In paper contact method, 72 h-LC50 values of carbofuran in
      M. posthuma and E. fetida were found to be 0.08 MUg/cm(2) and 1.55 MUg/cm(2)
      respectively while in soil test, 14-d LC50 values were 0.49 mg/kg and 21.15 mg/kg
      respectively. On comparing the toxicity data of these chemicals for both the
      earthworm species, M. posthuma was found to be more sensitive than E. fetida.
      Based on the acute toxicity data, the order of toxicity of insecticides in both
      the test procedures was carbofuran>cypermethrin>carbaryl>fenvalerate for M.
      posthuma whereas for E. fetida it was
      carbofuran>carbaryl>fenvalerate>cypermethrin. Morphological changes also appeared
      in the organisms exposed to these chemicals which were more pronounced in M.
      posthuma at lower concentrations than E. fetida in both the test procedures. The
      results of the present study advocates the use of M. posthuma for ecotoxicity
      studies, being a more sensitive and reliable model than E. fetida. Based on the
      data on partial atomic charges, structural features and spectroscopic studies on
      carbaryl and carbofuran, a possible mechanism of toxicity of carbamate
      insecticides in earthworm was proposed.

PMID- 24321851
TI  - Comparison of serious adverse events between the original and a generic docetaxel
      in breast cancer patients.
AB  - BACKGROUND: Generic formulations are not necessarily identical to the original in
      terms of efficacy and adverse events. Generic docetaxel has been available in
      Canada since 2011. OBJECTIVE: To compare the occurrence of grade III to IV
      adverse events between original docetaxel and a generic formulation in breast
      cancer patients. METHODS: A consecutive series of 400 patients were assessed
      retrospectively: 200 who received the original docetaxel and 200 who received a
      generic formulation. Patients who received both formulations or received their
      chemotherapy outside our center were excluded. The primary outcome was the
      occurrence of grade III to IV adverse events related to docetaxel (febrile
      neutropenia, hand and foot syndrome, intestinal perforation, thrombotic event,
      and death). RESULTS: Three hundred-sixty-four patients were available for
      analysis (182/group). The use of a granulocyte colony-stimulating factor (G-CSF)
      was more frequent in the generic group (44.5% vs 28.8%), as well as treatment
      discontinuation (26.4% vs 14.8%). The occurrence of grade III to IV febrile
      neutropenia, hand and foot syndrome, intestinal perforation, thrombotic event,
      and docetaxel-related deaths were similar between the 2 formulations. However,
      grade IV febrile neutropenia was more frequent with the generic formulation
      (78.8% vs 56.3%). Limitations were the retrospective nature of the study and the
      variety of chemotherapy regimens. CONCLUSION: Adverse events occurrence was
      similar between the 2 formulations. However, febrile neutropenia was more serious
      with generic docetaxel, despite increased G-CSF use. Results suggest that the
      studied generic formulation may be safe, but more caution during treatments might
      be warranted, especially concerning febrile neutropenia events.

PMID- 24321852
TI  - Collaborative practice model between cardiologists and clinical pharmacists for
      management of patients with cardiovascular disease in an outpatient clinic.
AB  - The increasing prevalence of cardiovascular disease (CVD) has prompted leading
      cardiovascular organizations to advocate utilization of a team approach to
      patient care that includes nonphysician providers. In spite of that, the American
      College of Cardiology reported that nonphysician providers are underutilized in
      the management of patients with CVD. A survey of cardiologists revealed that the
      underutilization is a result of lack of understanding of how best to involve
      nonphysician providers in the health care team. Clinical pharmacists are one
      category of nonphysician providers that have recognized effectiveness in managing
      patients with CVD. No example of a comprehensive model of collaboration between
      cardiologists and clinical pharmacists is described in the literature that could
      serve to close this gap in understanding. The objective of this report is to
      describe a model of cardiologist-clinical pharmacist collaboration in the
      longitudinal management of patients with CVD that has been successfully
      implemented in 2 diverse settings. The implementation, evolution, scope of
      practice, required pharmacist training, logistical elements needed for success,
      and implementation barriers are reviewed. A summary of the patients referred to
      the clinic are examined as well. 

PMID- 24321853
TI  - Evaluation of impact of statin use on development of CPK elevation during
      daptomycin therapy.
AB  - BACKGROUND: Because both daptomycin and statins may increase creatine
      phosphokinase (CPK) levels, the manufacturer of daptomycin suggests considering
      holding statins during daptomycin therapy. Published evidence suggests potential
      detrimental effects of withdrawing statin therapy. OBJECTIVES: The objectives of
      this study were to determine the impact of concurrent statin therapy on peak CPK
      values, incidence of CPK elevation in patients receiving daptomycin therapy, and
      clinical factors associated with increased risk of developing CPK elevation.
      METHODS: This was a single-center, retrospective cohort study of patients >=18
      years of age who received daptomycin for >=72 hours and had >=1 follow-up CPK
      during a 5-year period. A Kaplan-Meier curve was used to evaluate time to CPK
      elevation. Cox regression analyses were used to compare the risk of developing
      elevated CPK between 3 study groups: those receiving daptomycin alone, daptomycin
      with concurrent statin therapy, and statin therapy held while on daptomycin.
      RESULTS: 498 patients were included in the study-384 received daptomycin alone,
      63 received daptomycin concurrent with statin, and 51 with statin held during
      daptomycin therapy. Cumulative incidence of CPK elevation was 5.1% and 12% at 7
      and 14 days. Those on daptomycin and statin concurrent therapy demonstrated an
      approximately 2-fold risk of CPK elevation compared with those having their
      statin therapy held, but the overall group effect was not statistically
      significant (P = .17). CONCLUSIONS: Our findings suggest that holding statin
      during daptomycin therapy may not be necessary, but may indicate need for
      increased frequency of CPK monitoring when these medications are used
      concurrently.

PMID- 24321854
TI  - House of care approach for patients with long term conditions works at the local
      level.

PMID- 24321855
TI  - First full-beam PET acquisitions in proton therapy with a modular dual-head
      dedicated system.
AB  - During particle therapy irradiation, positron emitters with half-lives ranging
      from 2 to 20 min are generated from nuclear processes. The half-lives are such
      that it is possible either to detect the positron signal in the treatment room
      using an in-beam positron emission tomography (PET) system, right after the
      irradiation, or to quickly transfer the patient to a close PET/CT scanner. Since
      the activity distribution is spatially correlated with the dose, it is possible
      to use PET imaging as an indirect method to assure the quality of the dose
      delivery. In this work, we present a new dedicated PET system able to operate in
      beam. The PET apparatus consists in two 10 cm * 10 cm detector heads. Each
      detector is composed of four scintillating matrices of 23 * 23 LYSO crystals. The
      crystal size is 1.9 mm * 1.9 mm * 16 mm. Each scintillation matrix is read out
      independently with a modularized acquisition system. The distance between the two
      opposing detector heads was set to 20 cm. The system has very low dead time per
      detector area and a 3 ns coincidence window, which is capable to sustain high
      single count rates and to keep the random counts relatively low. This allows a
      new full-beam monitoring modality that includes data acquisition also while the
      beam is on. The PET system was tested during the irradiation at the CATANA (INFN,
      Catania, Italy) cyclotron-based proton therapy facility. Four acquisitions with
      different doses and dose rates were analysed. In all cases the random to total
      coincidences ratio was equal or less than 25%. For each measurement we estimated
      the accuracy and precision of the activity range on a set of voxel lines within
      an irradiated PMMA phantom. Results show that the inclusion of data acquired
      during the irradiation, referred to as beam-on data, improves both the precision
      and accuracy of the range measurement with respect to data acquired only after
      irradiation. Beam-on data alone are enough to give precisions better than 1 mm
      when at least 5 Gy are delivered. 

PMID- 24321856
TI  - Updated treatment and prevention guidelines for pertussis.
AB  - Pertussis, commonly referred to as whooping cough, is one of the top 10 causes of
      death in children globally despite vaccine availability. Adhering to vaccination
      guidelines for both the primary childhood series as well as adolescent and adult
      boosters is crucial in preventing the spread of disease. However, due to vaccine
      failure, outbreaks occur every 3 to 5 years. As a result, early recognition and
      prompt treatment are instrumental in controlling the epidemic. 

PMID- 24321857
TI  - Molecular mechanisms of hyperthermia-induced apoptosis enhanced by withaferin A.
AB  - Hyperthermia is a good therapeutic tool for non-invasive cancer therapy; however,
      its cytotoxic effects are not sufficient. In the present study, withaferin A
      (WA), a steroidal lactone derived from the plant Withania somnifera Dunal, has
      been investigated for its possible enhancing effects on hyperthermia-induced
      apoptosis. In HeLa cells, treatment with 0.5 or 1.0MUM WA at 44 degrees C for
      30min induced significant apoptosis accompanied by decreased intracellular
      GSH/GSSG ratio and caspase-3 activation, while heat or WA alone did not induce
      such changes. The upregulation in apoptosis was significantly inhibited by
      glutathione monoethyl ester, a cell permeable glutathione precursor.
      Mitochondrial transmembrane potentials were dramatically decreased by the
      combined treatment, with increases in pro-apoptotic Bcl-2-family proteins tBid
      and Noxa, and downregulation of antiapoptotic Bcl-2 and Mcl-1. Combined treatment
      with hyperthermia and WA induced significant increases in JNK phosphorylation (p
      JNK), and decreases in the phosphorylation of ERK (p-ERK) compared with either
      treatment alone. These results suggest that WA enhances hyperthermia-induced
      apoptosis via a mitochondria-caspase-dependent pathway; its underlying mechanism
      involves elevated intracellular oxidative stress, mitochondria dysfunction, and
      JNK activation. 

PMID- 24321859
TI  - Plasmonic films based on colloidal lithography.
AB  - This paper reviews recent advances in the field of plasmonic films fabricated by
      colloidal lithography. Compared with conventional lithography techniques such as
      electron beam lithography and focused ion beam lithography, the unconventional
      colloidal lithography technique with advantages of low-cost and high-throughput
      has made the fabrication process more efficient, and moreover brought out novel
      films that show remarkable surface plasmon features. These plasmonic films
      include those with nanohole arrays, nanovoid arrays and nanoshell arrays with
      precisely controlled shapes, sizes, and spacing. Based on these novel
      nanostructures, optical and sensing performances can be greatly enhanced. The
      introduction of colloidal lithography provides not only efficient fabrication
      processes but also plasmonic films with unique nanostructures, which are
      difficult to be fabricated by conventional lithography techniques. 

PMID- 24321858
TI  - Mannose-binding lectin genetic analysis: possible protective role of the HYPA
      haplotype in the development of recurrent urinary tract infections in men.
AB  - Factors related to bacterial virulence and/or to the host have been implicated in
      the pathogenesis of recurrent urinary tract infections (rUTI), but in most cases
      the cause is unknown. Mannose binding lectin (MBL) is an acute phase glycoprotein
      that exerts immunological functions by binding to the surface of a variety of
      pathogens. Some human gene variants reduce MBL activity thereby predisposing the
      host to bacterial and viral infections. The aim of this study was to investigate
      MBL2 gene variants in relation to rUTI risk. Six MBL gene variants and seven
      haplotypes were analyzed by PCR and direct sequencing in rUTI patients (n = 83)
      and in healthy subjects from southern Italy (n = 642). The frequencies of the L
      allele (-550) and the HYPA haplotype were higher in controls than in patients
      stratified according to sex (p < 0.05). Our data indicate that the HYPA haplotype
      in the MBL2 gene could be associated with a minor risk of developing rUTI in
      males. 

PMID- 24321860
TI  - Surface shear rheology of monolayers at the surface of water.
AB  - The knowledge of surface shear rheology is important to understand and model flow
      in systems where interfaces are present: multiphase flow, wetting, foaming and
      others. The topic has been investigated for more than 100 years, but the
      knowledge accumulated is still partial. The experimental devices used for the
      measurement of the viscoelastic parameters are delicate to operate and the
      response of the monolayers is complex, usually non-linear and time dependent.
      Furthermore, it is difficult to decouple from the response of the bulk liquid.
      Important discrepancies between microscopic and macroscopic methods were reported
      and remain to be clarified. The knowledge of shear properties does not suffice in
      general to achieve proper descriptions of the flow behavior and measurements of
      compression properties are needed as well. This paper presents examples taken
      from the literature and discusses the current level of understanding.

PMID- 24321861
TI  - Stabilization of layer-by-layer engineered multilayered hollow microspheres.
AB  - Polymer multilayered hollow microspheres prepared by layer-by-layer (LbL) self
      assembly attract more and more interest due to their unique application,
      especially as drug delivery system (DDS). Unfortunately, the multilayered hollow
      microspheres assembled via weak linkages could fuse and/or aggregate in high
      ionic strength media or strong acidic or basic media. This severely restricts the
      practical applications of the multilayered hollow microspheres as DDS in human
      physiological medium. In the present work, the progress in stabilization of the
      multilayered hollow microspheres is reviewed, with emphasis on the assembling
      process and their crosslinking mechanism. 

PMID- 24321862
TI  - [Role of GnRH agonists in preserving female fertility].
AB  - The impact of cancer treatment on ovarian function and fertility has been known
      since the 70s. Preservation of fertility is now an important focus of care for
      patients of reproductive age with cancer. The beneficial role of GnRH agonists in
      fertility preservation is controversial since the early 2000s. Recent randomized
      studies come to overturn this role. The POEMS multicenter randomized trial with
      long-term follow-up is ongoing and will provide results that could help clarify
      the current uncertain indication of these compounds in this context. 

PMID- 24321863
TI  - Does the name really matter? The importance of botanical nomenclature and plant
      taxonomy in biomedical research.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medical research on plant-derived compounds
      requires a breadth of expertise from field to laboratory and clinical skills. Too
      often basic botanical skills are evidently lacking, especially with respect to
      plant taxonomy and botanical nomenclature. Binomial and familial names, synonyms
      and author citations are often misconstrued. The correct botanical name, linked
      to a vouchered specimen, is the sine qua non of phytomedical research. Without
      the unique identifier of a proper binomial, research cannot accurately be linked
      to the existing literature. Perhaps more significant, is the ambiguity of species
      determinations that ensues of from poor taxonomic practices. This uncertainty,
      not surprisingly, obstructs reproducibility of results-the cornerstone of
      science. MATERIALS AND METHODS: Based on our combined six decades of experience
      with medicinal plants, we discuss the problems of inaccurate taxonomy and
      botanical nomenclature in biomedical research. This problems appear all too
      frequently in manuscripts and grant applications that we review and they extend
      to the published literature. We also review the literature on the importance of
      taxonomy in other disciplines that relate to medicinal plant research. RESULTS
      AND DISCUSSION: In most cases, questions regarding orthography, synonymy, author
      citations, and current family designations of most plant binomials can be
      resolved using widely-available online databases and other electronic resources.
      Some complex problems require consultation with a professional plant taxonomist,
      which also is important for accurate identification of voucher specimens.
      Researchers should provide the currently accepted binomial and complete author
      citation, provide relevant synonyms, and employ the Angiosperm Phylogeny Group
      III family name. Taxonomy is a vital adjunct not only to plant-medicine research
      but to virtually every field of science. CONCLUSIONS: Medicinal plant researchers
      can increase the precision and utility of their investigations by following sound
      practices with respect to botanical nomenclature. Correct spellings, accepted
      binomials, author citations, synonyms, and current family designations can
      readily be found on reliable online databases. When questions arise, researcher
      should consult plant taxonomists.

PMID- 24321864
TI  - Chemical characterization of Centaurium erythrea L. and its effects on
      carbohydrate and lipid metabolism in experimental diabetes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythrea L. fam. Gentianaceae (CE) has
      been traditionally used for centuries in folk medicine of Balkans as a bitter
      medicinal herb for digestive complications and for treating febrile conditions
      and diabetes. The aim of this study was to gain insight into the chemical
      composition and underlying biochemical mechanism of action of the
      antihyperglycemic and antilipidemic activities of the dry extract of Centaurium
      erythrea L., wildly growing and traditionally used medicinal plant in the
      Republic of Macedonia. MATERIALS AND METHODS: An ultrasonic methanol maceration
      of the aerial parts of the dried plant was performed and the extract was freeze
      dried. HPLC-DAD-ESI-MS(n) was carried out on 150 mm * 4.6mm, 5 MUm RP-18 Eclipse
      XDB column, at 40  degrees C. Mobile phase: water with 1% formic acid (A) and
      methanol (B) with linear gradient starting with 10% B was used to reach 15% at 5
      min, 40% B at 25 min, 55% of B at 50 min and 100% at 60 min, with flow rate of
      0.4 mL min(-1). Normal and streptozotocin (STZ) hyperglycemic Wistar rats were
      used for assessment of the antihyperglycemic and antilipidemic activity by
      measurement of the key carbohydrate-related enzymes and substrates, as well as
      lipid state of the organism. RESULTS: HPLC-DAD-ESI-MS(n) analyses revealed
      presence of four different secoiridoids, seven flavonoid glycosides and seven
      xanthones in the freeze-dried extract of CE representing 53%, 25% and 22% of all
      compounds, respectively. The short-term (12 days) treatment of the STZ-diabetic
      rats with CE-extracts resulted in a 74% reduction of the produced hyperglycemia,
      which is only 6% less than the reduction caused by glibeclamide (GLB, positive
      control). The CE-extract had a significant impact on the hepatic carbohydrate
      metabolism enhancing the direct synthesis of glycogen, normalizing phosphorylase
      a activity and reducing the activity of glucose-6-phosphatase, which further
      causes reduction in production of blood glucose level. The long-term (45 days)
      treatment showed that the HbA1c in CE-treated group of animals was even lower
      than in the GLB-treated groups. The antilipidemic assessment of the CE-extract
      revealed decrease of total cholesterol, triglycerides, HDL and LDL level in the
      blood of the normal and STZ-hyperglycemic rats. CONCLUSION: The obtained results
      indicate that treatment with CE extract in STZ-diabetic rats regulates the
      elevated level of blood glucose and carbohydrate-related disturbances slightly
      better than the effect of glibenclamide. There was also regulation of the serum
      lipid status in diabetic rats. Identified groups of bitter compounds in the
      extract (flavonoides, iridoids and xanthones) probably have influence on the
      expressed antihyperglycaemic effect.

PMID- 24321865
TI  - Synthesis and biological evaluation of allylated and prenylated mono-carbonyl
      analogs of curcumin as anti-inflammatory agents.
AB  - Curcumin has been shown to possess anti-inflammatory activities but has been
      limited for its low stability and poor bioavailability. We have previously
      reported four series of 5-carbon linker-containing mono-carbonyl analogs of
      curcumin (MACs). In continuation of our ongoing research, we designed and
      synthesized 33 novel allylated or prenylated MACs here, and evaluated their anti
      inflammatory effects in RAW 264.7 macrophages. A majority of them effectively
      inhibited the LPS-induced expression of TNF-alpha and IL-6, especially IL-6. The
      preliminary SAR and quantitative SAR analysis were conducted. Compound 14q is the
      most potent analog among them, and exhibits significant protection against LPS
      induced death in septic mice. Together, these data present a series of new
      analogs of curcumin as promising anti-inflammatory agents. 

PMID- 24321866
TI  - On background radiation gradients--the use of airborne surveys when searching for
      orphan sources using mobile gamma-ray spectrometry.
AB  - Systematic background radiation variations can lead to both false positives and
      failures to detect an orphan source when searching using car-borne mobile gamma
      ray spectrometry. The stochastic variation at each point is well described by
      Poisson statistics, but when moving in a background radiation gradient the mean
      count rate will continually change, leading to inaccurate background estimations.
      Airborne gamma spectrometry (AGS) surveys conducted on the national level,
      usually in connection to mineral exploration, exist in many countries. These data
      hold information about the background radiation gradients which could be used at
      the ground level. This article describes a method that aims to incorporate the
      systematic as well as stochastic variations of the background radiation. We
      introduce a weighted moving average where the weights are calculated from
      existing AGS data, supplied by the Geological Survey of Sweden. To test the
      method we chose an area with strong background gradients, especially in the
      thorium component. Within the area we identified two roads which pass through the
      high-variability locations. The proposed method is compared with an unweighted
      moving average. The results show that the weighting reduces the excess false
      positives in the positive background gradients without introducing an excess of
      failures to detect a source during passage in negative gradients. 

PMID- 24321867
TI  - [Update on the management of acute viral bronchiolitis: proposed guidelines of
      Grand Ouest University Hospitals].
AB  - BACKGROUND AND OBJECTIVES: While our European and North American colleagues have
      recently updated their recommendations, the 2000 Consensus Conference remains the
      main guideline on management of acute viral bronchiolitis in France. We aimed to
      establish an updated inter-regional protocol on management of acute viral
      bronchiolitis in infants. METHOD: Pediatricians, pediatric pulmonologists, and
      emergency physicians of the Grand Ouest University Hospitals (France) gathered to
      analyze the recent data from the literature. RESULTS: Criteria to distinguish
      childhood asthma from acute viral bronchiolitis were established, then
      prescriptions of diagnostic tests, antibiotics, and chest physiotherapy were
      defined and reserved for very limited situations. Similarly, the modalities of
      oxygen therapy prescription and nutritional support were proposed. Finally, other
      therapeutics such as nebulized hypertonic saline seem promising, but their place
      in the treatment of acute bronchiolitis in infants remains unclear. CONCLUSION:
      This work has provided new proposals for management of acute viral bronchiolitis
      and helped standardize practices within the Grand Ouest University Hospitals.
      This local organization could lay the keystone for working toward guidelines
      initiated by learned societies at the national level.

PMID- 24321868
TI  - [L-2-hydroxyglutaric aciduria: report on two cases].
AB  - L-2-hydroxyglutaric aciduria is a rare genetic neurometabolic disease. It occurs
      in childhood with mental retardation, cerebellar ataxia, and epilepsy.
      Macrocephaly is present in half of the cases. Diagnosis is based on clinical
      symptoms, biological and radiological findings, and molecular testing. Specific
      treatments can improve the spontaneous progression of the disease. We examined
      two independent patients who presented with L-2-hydroxyglutaric aciduria.
      Clinical presentation led to cerebral MRI and urinary organic acid
      chromatography. The genetic analysis confirmed the diagnosis. Under specific
      treatment, the progression of the disease was subsequently stopped. L-2
      hydroxyglutaric aciduria shares common symptoms with other genetic and metabolic
      diseases. However, the association of a distinct phenotype and typical MRI
      abnormalities (such as a high signal in the subcortical white matter, pallidum,
      and dentate nuclei) should draw the clinician's attention to this diagnosis. It
      can easily be suspected with a simple urinary analysis and can then be confirmed
      by genetic testing. With this case report, we show the importance of genetic
      identification to begin treatment with riboflavin. Early detection of L-2
      hydroxyglutaric aciduria based on MRI abnormalities can enable rapid initiation
      of treatment and prevent disease progression. 

PMID- 24321869
TI  - [Place of socialization/communication learning groups in autism with moderate
      mental retardation].
AB  - Studies based on social skills training groups for people with autism always
      target people without mental retardation and the subjects are more often
      teenagers and adults than children. Quantitative and standardized psychometrics
      are not routinely studied. OBJECTIVES: Describing the changes in symptoms and
      social communication skills of five children with autism and moderate mental
      retardation, who participated in 20 sessions in a social skills training group
      appropriate to their developmental level. METHOD: Standardized scales to develop
      the target skills and applied behavioral analysis and structured techniques were
      implemented in these sessions. To measure changes, we assessed the children
      before and after the 20 sessions (Vineland Adaptative Behavior Scale and Autism
      Diagnostic Observation Schedule) and we noted whether or not of the target skills
      were achieved. RESULTS: The scores showed a significant improvement in autistic
      symptoms and social communication skills. CONCLUSION: The results show that this
      type of educational experience appears relevant to meeting objectives in social
      and communication skills. However, any conclusions as to a significant impact of
      the intervention are strongly limited by the absence of a control group.

PMID- 24321870
TI  - [Postinfectious family case of acute necrotizing encephalopathy caused by RANBP2
      gene mutation].
AB  - Acute necrotizing encephalopathy is a rare neurologic disease most often
      triggered by a febrile viral event affecting an otherwise healthy infant. The
      clinical course is characterized by rapid deterioration of the neurological
      condition that often leads to coma and requires intensive care. The diagnosis is
      usually suggested by MRI, which shows symmetrical and focal necrotic lesions of
      thalami. Acute necrotizing encephalopathy has been linked in recent studies to an
      autosomal-dominant mutation of the gene for the protein RAN-binding protein 2.
      CASE REPORT: We report three cases in siblings of Tunisian origin. Two of them
      presented with acute necrotizing encephalopathy at the age of 9 months in the
      immediate aftermath of a viral infection. The molecular study conducted in the
      family showed that both patients and their mother were carriers of the missense
      mutation gene RAN-binding protein 2. COMMENTS: Although the role of Ran BP2
      protein is incompletely known, mutation of the RANBP2 gene causes rare,
      reversible central neurologic disorders. Suspected diagnosis is facilitated by
      MRI, which shows specific lesions of multifocal, symmetric involvement of the
      thalami, brainstem tegmentum, supratentorial white matter, and cerebellum. Due to
      the low frequency of the disease and its non-specific clinical presentation, the
      diagnosis of acute necrotizing encephalopathy is a major challenge, while
      preventative measures can be proposed in familial mutation.

PMID- 24321871
TI  - [Evaluation of a new telephone counseling protocol used by the admission nurse of
      a pediatric emergency department].
AB  - INTRODUCTION: Telephone counseling is a daily occurrence in the pediatric
      emergency department (ED). It is difficult and has no legal framework. In 2010,
      we created a new protocol aimed at improving the telephone counseling given by
      the admission nurse at our pediatric emergency department: an index card is
      created for every call, color-coded according to severity with a list of clinical
      items, allowing for simple and reproducible advice. MATERIALS AND METHODS: The
      aim of this study was to evaluate the reliability of the cards. We conducted a
      prospective analysis, from June 2011 to January 2012, to analyze every card
      generated for seven major reasons for calling. The study was designed to: (a)
      measure the level of accurate completion of the cards by the admission nurse; (b)
      evaluate the quality of the advice given, as defined by the color coding.
      RESULTS: Of 3297 calls received, 1033 cards were included in the analysis: 504
      (49%) of these cards were correctly completed for optimal traceability (complete
      administrative and clinical data, correct color coding). The level of completion
      significantly increased for admission nurses who had filled in more than ten
      cards. Among these 504 calls, 386 cards (77%) delivered appropriate advice and 87
      (17%) inappropriate advice. Thirty-one cards (6%) could not be evaluated for the
      quality of the advice given. There was no significant difference between the
      different causes for calling. Overall, only ten calls (less than 2%) resulted in
      underestimation of the severity of the child's condition, and 9% in
      overestimation (leading to an unnecessary consultation in the ED). DISCUSSION:
      The quality of card completion needs to improve, especially since this study
      demonstrates how easy it is to use these cards. They ensure exhaustive
      questioning; guide the admission nurse toward safer advice, with appropriate
      advice given in 77% of cases. The rate of underestimated severity is low, and the
      initial severity of these cases is debatable because half of these cases
      consulted at the ED 12-24h after the initial call. CONCLUSION: These innovative
      color-coded cards make it possible to dispense reliable and harmonized advice.
      They ease the process of an otherwise difficult exercise.

PMID- 24321872
TI  - Temporal-spatial expression of ENOLASE after acute spinal cord injury in adult
      rats.
AB  - ENOLASE enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known
      for their role in glucose metabolism. Recent accumulation of evidence revealed
      that, in addition to its glycolytic function, enolase is also associated with
      ischemia, hypoxia and to be a neurotrophic factor. To analysis the certain
      expression and biological function in central nervous system, we performed an
      acute spinal cord contusion injury model in adult rats. Western blot analysis
      indicated a marked upregulation of ENOLASE after spinal cord injury (SCI).
      Immunohistochemistry revealed wide distribution of enolase in spinal cord,
      including neurons and glial cells. Double immunofluorescent staining for
      proliferating cell nuclear antigen and phenotype-specific markers showed
      increases of enolase expression in proliferating microglia and astrocytes. Our
      data suggest that enolase may be implicated in the proliferation of microglia and
      astrocytes after SCI. 

PMID- 24321873
TI  - How sensitive is Melissa officinalis to realistic ozone concentrations?
AB  - Lemon balm (Melissa officinalis, L.; Lamiaceae) was exposed to realistic ozone
      (O3) dosages (80 ppb for 5 h), because high background levels of O3 are
      considered to be as harmful as episodic O3 regimes. Temporal alterations of
      different ecophysiological, biochemical and structural parameters were
      investigated in order to test if this species can be considered as an O3
      bioindicator regarding changes in background concentrations. At the end of ozone
      exposure, the plants did not exhibit any visible foliar symptoms, as only at
      microscopic level a small number of dead cells were found. Photosynthetic
      processes, however, were significantly affected. During and after the treatment,
      ozone induced a reduction in CO2 fixation capacity (up to 52% after 12 h from the
      beginning of the treatment) due to mesophyllic limitations. Intercellular CO2
      concentration significantly increased in comparison to controls (+90% at the end
      of the post-fumigation period). Furthermore impairment of carboxylation
      efficiency (-71% at the end of the post-fumigation period compared to controls in
      filtered air) and membrane damage in terms of integrity (as demonstrated by a
      significant rise in solute leakage) were observed. A regulatory adjustment of
      photosynthetic processes was highlighted during the post-fumigation period by the
      higher values of qNP and (1-q(P)) and therefore suggests a tendency to reduce the
      light energy used in photochemistry at the expense of the capacity to dissipate
      the excess as excitation energy. In addition, the chlorophyll a/b ratio and the
      de-epoxidation index increased, showing a rearrangement of the pigment
      composition of the photosynthetic apparatus and a marked activation of
      photoprotective mechanisms.

PMID- 24321874
TI  - Carbon-nitrogen ratio and in vitro assimilate partitioning patterns in Cyrtanthus
      guthrieae L.
AB  - In response to variations in nutritional composition of the growth medium, plants
      often adjust their metabolism and progressively alter their growth patterns.
      Carbon (C) and nitrogen (N) constitute the major plant nutritional components
      influencing plant growth and development patterns. This study examined the growth
      dynamics and patterns of assimilate partitioning to primary and secondary
      metabolites in response to varying levels and combinations of C and N in the
      culture media of Cyrtanthus guthrieae. In vitro callus-derived C. guthrieae
      plantlets were cultured on solid Murashige and Skoog (MS) media with different
      concentrations and combinations of C and N. Relative growth rate (RGR) increased
      proportionally with an increase in C concentrations up to 88 mM sucrose (0.58 d(
      1)) beyond which it was hardly influenced by further increases in C. Growth was
      also significantly favoured in media with high concentrations of N at all C
      concentrations tested. In C-limited media regimes with growth saturating N
      conditions, alkaloid accumulation became favoured while polyphenol content
      increased with an increase in C levels in the medium, a characteristic pattern
      that appeared to be less influenced by the amount of N. Of the primary
      metabolites, only proteins showed small significant variations across different
      media treatments, with starch and soluble sugars increasing proportionately with
      C levels. In the medium with a high sucrose concentration (175 mM), soluble
      sugars, amino acids and polyphenols increased markedly, possibly as an adaptive
      response to the reduced osmotic potential in the media and/or a storage mechanism
      for excess C and N reserves in the media. From a medicinal perspective, with
      regard to polyphenolic compounds in C. guthrieae, growth medium conditions that
      allow for high levels of C pools in the tissue would thus be favourable for the
      enhanced synthesis of this group of compounds. The medium conditions with 175 mM
      sucrose and 10.3 mM NH4NO3 gave the highest total polyphenols, flavonoids and
      proanthocyanidins with a moderate growth rate.

PMID- 24321875
TI  - Low temperature inhibits pollen tube growth by disruption of both tip-localized
      reactive oxygen species and endocytosis in Pyrus bretschneideri Rehd.
AB  - Low temperature (LT) negatively affects fertilization processes of flowering
      plants. Pollen tube growth is generally inhibited under LT stress; however, the
      mechanism(s) underlying this inhibition remain(s) largely unknown. Pollen tubes
      are tip-growing and the presence of tip-localized reactive oxygen species (ROS)
      is necessary for cellular functioning. Disruption of tip-localized ROS was
      observed in pear pollen tubes in vitro under low temperature of 4  degrees C
      (LT4). Diphenylene iodonium chloride, an NADPH oxidase (NOX) inhibitor,
      suppressed hydrogen peroxide formation in the cell walls of the subapical region
      in pear pollen tubes. Under LT4 stress, ROS disruption in pear pollen tubes
      mainly resulted from decreased NOX activity in the plasma membrane, indicating
      that NOX was the main source of ROS in this process. Moreover, LT4 remarkably
      decreased mitochondrial oxygen consumption and intracellular ATP production. The
      endocytosis, an energy-dependent process, disruption in pear pollen tubes under
      LT4 may be mediated by mitochondrial metabolic dysfunctions. Our data showed ROS
      and endocytosis events in pear pollen tubes responding to LT4 stress.

PMID- 24321876
TI  - Genome-wide identification and characterization of polygalacturonase genes in
      Cucumis sativus and Citrullus lanatus.
AB  - Polygalacturonase (PG, EC3.2.1.15), one of the hydrolytic enzymes associated with
      the modification of pectin network in plant cell wall, has an important role in
      various cell-separation processes that are essential for plant development. PGs
      are encoded by a large gene family in plants. However, information on this gene
      family in plant development remains limited. In the present study, 53 and 62
      putative members of the PG gene family in cucumber and watermelon genomes,
      respectively, were identified by genome-wide search to explore the composition,
      structure, and evolution of the PG family in Cucurbitaceae crops. The results
      showed that tandem duplication could be an important factor that contributes to
      the expansion of the PG genes in the two crops. The phylogenetic and evolutionary
      analyses suggested that PGs could be classified into seven clades, and that the
      exon/intron structures and intron phases were conserved within but divergent
      between clades. At least 24 ancestral PGs were detected in the common ancestor of
      Arabidopsis and Cucumis sativus. Expression profile analysis by quantitative real
      time polymerase chain reaction demonstrated that most CsPGs exhibit specific or
      high expression pattern in one of the organs/tissues. The 16 CsPGs associated
      with fruit development could be divided into three subsets based on their
      specific expression patterns and the cis-elements of fruit-specific,
      endosperm/seed-specific, and ethylene-responsive exhibited in their promoter
      regions. Our comparative analysis provided some basic information on the PG gene
      family, which would be valuable for further functional analysis of the PG genes
      during plant development. 

PMID- 24321878
TI  - Effectiveness of influenza vaccination in institutionalized older adults: a
      systematic review.
AB  - INTRODUCTION: Influenza infection is common among institutionalized older adults.
      Many nonrandomized observational studies on influenza vaccination suggested that
      it could reduce influenza-related hospitalizations and mortality in
      institutionalized older adults. Criticism regarding the effectiveness of
      influenza vaccine estimated by nonrandomized observational studies include the
      frailty selection bias and use of nonspecific outcome, such as all-cause
      mortality. METHODS: We conducted a systematic review of studies of influenza
      vaccination in institutionalized older adults to determine the effects on
      clinical outcomes. We searched for studies from 3 databases from 1946 to June
      2013 assessing effectiveness against influenza infection. We selected studies
      with good comparability between vaccine group and control group. We expressed
      vaccine effectiveness (VE) as a proportion, using the formula VE = 1-relative
      risk or 1-odds ratio. We focused on the following outcomes: influenza-like
      illness (ILI), laboratory confirmed influenza, hospitalizations due to ILI, or
      pneumonia and death due to influenza or pneumonia. We did not include all-cause
      mortality. RESULTS: Eleven studies that satisfied the inclusion criteria were
      identified, representing 11,262 institutionalized older adults. After meta
      analysis, we found a significant reduction in pneumonia (VE: 37%, 95% confidence
      interval [CI]: 18%-53%, P = .001) and death due to pneumonia or influenza (VE:
      34%, CI: 10%-53%, P = .01). There was no significant heterogeneity between
      studies. There was no significant publication bias. CONCLUSION: Influenza
      vaccination in institutionalized older adults could reduce pneumonia and death
      due to pneumonia or influenza. Influenza vaccination is recommended for
      institutionalized older adults.

PMID- 24321879
TI  - Effects of bariatric surgery on cardiac structure and function: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Morbid obesity, a condition increasingly treated with bariatric
      procedures, is strongly associated with left ventricular (LV) hypertrophy and
      impaired LV function. We analyzed the literature to provide comprehensive
      information on cardiac structural and functional changes, as assessed by imaging
      techniques, after bariatric surgery. METHODS: The studies were identified by the
      following search terms: "bariatric surgery," "obesity," "left ventricle," "left
      ventricular hypertrophy," "cardiac hypertrophy," "ventricular dysfunction," "left
      ventricular hypertrophy regression," "echocardiography," "magnetic resonance
      imaging," and "cardiac imaging techniques." RESULTS: In a pooled population of
      1,022 obese subjects with preserved systolic function included in 23 studies,
      bariatric procedures induced (i) a decrease in LV mass (standardized mean
      difference (SMD) = -0.46; P < 0.001) and relative wall thickness (SMD = -0.20; P
      < 0.001); (ii) an improvement of LV diastolic function, as reflected by the
      increase in mitral flow E/A ratio (SMD = +0.39; P < 0.001); (iii) a decrease in
      left atrium diameter (SMD = -0.26; P < 0.001); or (iv) no changes in LV ejection
      fraction (SMD = +0.03; P = 0.46). CONCLUSIONS: The present meta-analysis, the
      largest to date focusing on cardiac structural and functional changes in morbidly
      obese subjects after bariatric surgery, documents that this therapeutic approach
      exerts important cardioprotective effects in terms of regression of LV
      hypertrophy, improvement of LV geometry and diastolic function, and reduction of
      left atrial size.

PMID- 24321880
TI  - Comparison of metal accumulation in the azooxanthellate scleractinian coral
      (Tubastraea coccinea) from different polluted environments.
AB  - The response of metal accumulation in coral Tubastraea coccinea to various
      degrees of metal enrichment was investigated from the Yin-Yang Sea (YYS)
      receiving abandoned mining effluents, the Kueishan Islet (KI) hydrothermal vent
      field, and the nearshore area of remoted Green Island (GI). The concentrations of
      most dissolved metals were highest in seawater at YYS, followed by KI, and then
      GI, showing the effects of anthropogenic and venting inputs on metal levels. Five
      metals (Co, Fe, Mn, Ni, and Zn) yielded significant differences (p<0.05) among
      the skeleton samples. We identified similar patterns in the metal-Ca ratios,
      indicating that the elevated metals in skeletons was a consequence of external
      inputs. The coral tissues were relatively sensitive in monitoring metal
      accumulation, showing significant differences among three locations for Cd, Co,
      Cu, Fe, Pb, Ni, and Zn. Specific bioconcentration factors provided strong support
      for the differential metal accumulation in skeletons and tissues. 

PMID- 24321881
TI  - Plastic debris retention and exportation by a mangrove forest patch.
AB  - An experiment observed the behavior of selected tagged plastic items deliberately
      released in different habitats of a tropical mangrove forest in NE Brazil in late
      rainy (September) and late dry (March) seasons. Significant differences were not
      reported among seasons. However, marine debris retention varied among habitats,
      according to characteristics such as hydrodynamic (i.e., flow rates and volume
      transported) and relative vegetation (Rhizophora mangle) height and density. The
      highest grounds retained significantly more items when compared to the borders of
      the river and the tidal creek. Among the used tagged items, PET bottles were more
      observed and margarine tubs were less observed, being easily transported to
      adjacent habitats. Plastic bags were the items most retained near the releasing
      site. The balance between items retained and items lost was positive,
      demonstrating that mangrove forests tend to retain plastic marine debris for long
      periods (months-years). 

PMID- 24321882
TI  - Self-powered biosensor for ascorbic acid with a Prussian blue electrochromic
      display.
AB  - We report on the development of a nanocarbon based anode for sensing of ascorbic
      acid (AA). The oxidation of AA on this anode occurs at a quite low overpotential
      which enables the anode to be connected to a biocathode to form an ascorbic
      acid/O2 biofuel cell that functions as a self-powered biosensor. In conjunction
      with a Prussian blue electrochromic display the anode can also work as a truly
      self-powered sensor. The oxidation of ascorbic acid at the anode leads to a
      reduction of the Prussian blue in the display. The reduced form of Prussian blue,
      called Prussian white, is transparent. The rate of change from blue to colourless
      is dependent on the concentration of ascorbic acid. The display can easily be
      regenerated by connecting it to the biocathode which returns the Prussian blue to
      its oxidized form. In this way we have created the first self-powered
      electrochromic sensor that gives quantitative information about the analyte
      concentration. This is demonstrated by measuring the concentration of ascorbic
      acid in orange juice. The reported quantitative read-out electrochromic display
      can serve as a template for the creation of cheap, miniturizable sensors for
      other relevant analytes. 

PMID- 24321883
TI  - Testing synthetic amyloid-beta aggregation inhibitor using single molecule atomic
      force spectroscopy.
AB  - Alzheimer's disease is a neurodegenerative disease with no known cure and few
      effective treatment options. The principal neurotoxic agent is an oligomeric form
      of the amyloid-beta peptide and one of the treatment options currently being
      studied is the inhibition of amyloid aggregation. In this work, we test a novel
      pseudopeptidic aggregation inhibitor designated as SG1. SG1 has been designed to
      bind at the amyloid-beta self-recognition site and prevent amyloid-beta from
      misfolding into beta sheet. We used atomic force spectroscopy, a nanoscale
      measurement technique, to quantify the binding forces between two single amyloid
      peptide molecules. For the first time, we demonstrate that single molecule atomic
      force spectroscopy can be used to assess the effectiveness of amyloid aggregation
      inhibitors by measuring the experimental yield of binding and can potentially be
      used as a screening technique for quick testing of efficacy of inhibitor drugs
      for amyloid aggregation. 

PMID- 24321884
TI  - Biosensing enhancement using passive mixing structures for microarray-based
      sensors.
AB  - The combination of microarray technologies with microfluidic sample delivery and
      real-time detection methods has the capability to simultaneously monitor 10-1000
      s of biomolecular interactions in a single experiment. Despite the benefits that
      microfluidic systems provide, they typically operate in the laminar flow regime
      under mass transfer limitations, where large analyte depletion layers act as a
      resistance to analyte capture. By locally stirring the fluid and delivering fresh
      analyte to the capture spot, the use of passive mixing structures in a microarray
      environment can reduce the negative effects of these depletion layers and enhance
      the sensor performance. Despite their large potential, little attention has been
      given to the integration of these mixing structures in microarray sensing
      environments. In this study, we use passive mixing structures to enhance the mass
      transfer of analyte to a capture spot within a microfluidic flow cell. Using
      numerical methods, different structure shapes and heights were evaluated as means
      to increase local fluid velocities, and in turn, rates of mass transfer to a
      capture spot. These results were verified experimentally via the real-time
      detection of 20-mer ssDNA for an array of microspots. Both numerical and
      experimental results showed that a passive mixing structure situated directly
      over the capture spot can significantly enhance the binding rate of analyte to
      the sensing surface. Moreover, we show that these structures can be used to
      enhance mass transfer in experiments regarding an array of capture spots. The
      results of this study can be applied to any experimental system using
      microfluidic sample delivery methods for microarray detection techniques.

PMID- 24321885
TI  - Sensitive and selective real-time electrochemical monitoring of DNA repair.
AB  - Unrepaired DNA damage can lead to mutation, cancer, and death of cells or
      organisms. However, due to the subtlety of DNA damage, it is difficult to sense
      the presence of damage repair with high selectivity and sensitivity. We have
      shown sensitive and selective electrochemical sensing of 8-oxoguanine and uracil
      repair glycosylase activity within DNA monolayers on gold by multiplexed analysis
      with silicon chips and low-cost electrospun nanofibers. Our approach compared the
      electrochemical signal of electroactive, probe-modified DNA monolayers containing
      a base defect versus the rational control of defect-free monolayers. We found
      damage-specific sensitivity thresholds on the order of femtomoles of proteins and
      dynamic ranges of over two orders of magnitude for each target. Temperature
      dependent kinetics were extracted, showing exponential signal loss with time
      constants of seconds. Damage specific detection in a mixture of enzymes and in
      response to environmental oxidative damage was also demonstrated. Nanofibers were
      shown to behave similarly to conventional gold-on-silicon devices, showing the
      potential of these low-cost devices for sensing applications. This device
      approach achieves a sensitive, selective, and rapid assay of repair protein
      activity, enabling a biological interrogation of DNA damage repair. 

PMID- 24321886
TI  - A label-free electrochemiluminescence aptasensor for thrombin detection based on
      host-guest recognition between tris(bipyridine)ruthenium(II)-beta-cyclodextrin
      and aptamer.
AB  - An ultrasensitive label-free electrochemiluminescence (ECL) aptasensor for the
      detection of thrombin was developed based on the specific recognition between
      tris(bipyridine)ruthenium(II)-beta-cyclodextrin (tris(bpyRu)-beta-CD) and the
      anti-thrombin aptamer (aptamer). The NH2-aptamer was first immobilized on the
      activated glassy carbon electrode (GCE) by coupling interaction. By use of the
      specific recognition between tris(bpyRu)-beta-CD and aptamer, tris(bpyRu)-beta-CD
      was then attached on the surface of GCE. Resulting from the outstanding
      photoactive properties of tris(bpyRu)-beta-CD, the fabricated GCE performed
      strong ECL signal with the coreactant of 2-(dibutylamino)ethanol (DBAE). However,
      in the presence of thrombin, aptamer-thrombin bioaffinity complexes were formed,
      which restricted the recognition activities between aptamer and tris(bpyRu)-beta
      CD. Thus, fewer tris(bpyRu)-beta-CD could be attached on the surface of GCE and
      led to an obvious decrease of ECL signal. Fortunately, the difference of ECL
      intensity before and after combination with thrombin was logarithmically linear
      with the concentration of thrombin in a wide range of 10 nM-1 pM. Meantime, a
      detection limit of 0.1 pM without any other signal labeling or amplifying
      procedures indicated that the biosensor performed excellent sensitivity,
      operability and simplicity.

PMID- 24321887
TI  - Multilocus sequence typing system (MLST) reveals a significant association of
      Entamoeba histolytica genetic patterns with disease outcome.
AB  - The relationship between parasite genotypes and outcome of amoebic infection is
      still a paradox and needed to be explored. Proper identification and genetic
      characterization of Entamoeba histolytica clinical isolates is an effective tool
      for exploring this relation. Along with conventional polymorphic marker
      (Chitinase), tRNA linked short tandem repeat (STR) loci has been employed as
      multilocus genotyping tool due to its better resolution and evolutionary
      significance. Some common as well as exclusive repeat patterns showing
      significant relation with disease outcome have been identified. Phylogenetic
      analysis revealed that repeat patterns exclusively found in asymptomatic and
      amoebic liver abscess derived isolates are placed in a common lineage and has
      similar association pattern with the disease outcome. Assumption can be made that
      isolates of E. histolytica remaining asymptomatic is genetically closer siblings
      of those causing liver abscess rather than the diarrheal isolates. 

PMID- 24321888
TI  - A novel anti-microbial function for a familiar Rab GTPase.
AB  - Salmonella enterica is a bacterial pathogen that closely interacts with its host
      and replicates intracellularly. It has evolved the ability to create an
      intracellular membrane vacuole where it can survive and replicate. The nature of
      the Salmonella vacuole is still poorly understood, and although it has some
      features in common with lysosomes, it serves as a suitable niche for its
      survival. In contrast to broad-host Salmonella enterica serovars, Salmonella
      enterica serovar Typhi (S. Typhi) is a host-adapted pathogen that does not have
      the ability to replicate in any species other than humans. Such host adaptation
      is manifested at the single cell level since this pathogen is unable to survive
      in non-human macrophages. We recently reported that a pathway dependent on the
      Rab GTPase Rab32 and its guanine-nucleotide exchange factor BLOC-3 restricts the
      growth and survival of S. Typhi in non-permissive macrophages. We also found that
      broad host Salmonellae, such as S. Typhimurium, are able to antagonize this
      pathway by delivering a bacterial effector protein that specifically cleaves
      Rab32 resulting in its degradation. 

PMID- 24321889
TI  - Ocular hypotensive efficacy of Src-family tyrosine kinase inhibitors via
      different cellular actions from Rock inhibitors.
AB  - We investigated the effects of Src-family tyrosine kinase (SFK) inhibitors on
      intraocular pressure (IOP) and trabecular meshwork (TM) cells. The SFK
      inhibitors, PP2, PP1, and damnacanthal, significantly lowered IOP from baseline
      following intracameral injection in ocular normotensive rabbits, and PP2
      decreased trans-epithelial electrical resistance (TEER) of TM cell layers in a
      dose-dependent manner ranging from 0.1 MUM to 100 MUM. The maximal efficacy of
      PP2 on TEER was a reduction to 71.7% relative to the vehicle-treated group at 100
      MUM. PP2 decreased the adhesion of TM cells to culture surfaces either uncoated
      with specific ECM proteins dose-dependently or coated with extracellular matrix
      proteins such as laminin I, fibronectin, collagen type I and basement membrane
      extraction. Tyrosine phosphorylation of focal adhesion kinase and p130(cas) was
      decreased by PP2. On the other hand, major changes in actin staining of TM cells
      were not able to be detected after PP2 treatment, although quantitative analysis
      showed that PP2 induced some morphological changes which were in the different
      direction to those caused by Y-27632, a Rock inhibitor. Y-27632 at 10 MUM
      increased the permeability of TM cell layers, but did not induce changes in the
      adhesion of TM cells. These results suggest that SFK inhibitors lower IOP, at
      least partly, by acting on TM cells in a manner that is distinct from Rock
      inhibitors. 

PMID- 24321890
TI  - Memory and orientation in the logopenic and nonfluent subtypes of primary
      progressive aphasia.
AB  - Memory and orientation were investigated as predictors of underlying Alzheimer's
      disease (AD) pathology in patients with logopenic (lv) and non-fluent (na)
      variants of primary progressive aphasia (PPA). Memory and orientation scores from
      Addenbrooke's Cognitive Examination were compared between 26 lv-PPA, 29 na-PPA,
      59 AD, and 90 controls using analysis of variance. Forty-five patients underwent
      Pittsburgh compound B (PiB) positron emission tomography scans. Patients with lv
      PPA performed poorer on memory and orientation than na-PPA and did not differ
      from the AD group. Post-hoc analysis on the PiB-scanned subgroup corroborated
      these results. Memory and orientation profiles may supplement language assessment
      in identifying patients with AD pathology. 

PMID- 24321891
TI  - Risk factors for cognitive decline in elderly people: findings from the two-year
      follow-up study in a Shanghai urban community.
AB  - BACKGROUND: The prevalence of cognitive impairment (CI) and its associated risk
      factors among elderly peoples in China has been investigated. However, dynamic
      studies revealing the risk factors associated with cognitive decline from follow
      up observations in China are rarely performed. OBJECTIVE: The present study aimed
      to identify factors predicting late-life cognitive decline in China. METHODS:
      Participants were 223 community-dwelling residents (>=65 years old) from the
      urban community of Shanghai with no CI upon comprehensive assessments at
      baseline. Cognitive decline at 2-year follow-up was defined as a drop of two or
      more points from baseline score in the Mini-Mental State Examination (MMSE).
      Associations with baseline demographic, lifestyle, health, and medical factors
      were then determined within the population. RESULTS: After 2 years, cognitive
      decline and incident CI developed in 75 (33.6%) and 25 (11.2%) participants,
      respectively. Across all participants, risk factors for cognitive decline
      included low education, high body mass index, and diabetes mellitus. Among
      participants with cognitive decline, points were predominantly lost in items
      relating to time orientation and complex commands in the MMSE. CONCLUSION: This
      study confirms the differences in risk factors between cross-sectional and
      longitudinal studies for cognitive decline among the elderly population in urban
      Shanghai. Interventions tailored to potential risk factors associated with
      cognitive decline may offer further benefits.

PMID- 24321877
TI  - The costs of dementia from the societal perspective: is care provided in the
      community really cheaper than nursing home care?
AB  - OBJECTIVE: To compare the costs of care for community-dwelling dementia patients
      with the costs of care for dementia patients living in nursing homes from the
      societal perspective. DESIGN: Cross-sectional bottom-up cost of illness study
      nested within the multicenter German AgeCoDe-cohort. SETTING: Community and
      nursing homes. PARTICIPANTS: One hundred twenty-eight community-dwelling dementia
      patients and 48 dementia patients living in nursing homes. INTERVENTION: None.
      MEASUREMENTS: Utilization and costs of medical care and long term care, including
      formal and informal social and nursing care based on proxy interviews. Informal
      care was valued using the replacement cost method. RESULTS: Unadjusted mean
      annual total costs including informal care were ?29,930 ($43,997) for community
      dwelling patients and ?33,482 ($49,218) for patients living in nursing homes.
      However, multiple regression analysis controlling for age, sex, deficits in basic
      and instrumental activities of daily living and comorbidity showed that living in
      the community significantly increased total costs by ?11,344 ($16,676; P < .01)
      compared with living in a nursing home, mainly due to higher costs of informal
      care (+?20,585; +$30,260; P < .001). CONCLUSION: From the societal perspective
      care for dementia patients living in the community tends to cost more than care
      in nursing homes when functional impairment is controlled for.

PMID- 24321892
TI  - Different adenosine A2A receptor expression in peripheral cells from elderly
      patients with vascular dementia and Alzheimer's disease.
AB  - The line between vascular dementia (VaD) and Alzheimer's disease (AD) is often
      blurred. In this study we investigated whether adenosine A2A receptor (A2AR)
      expression can be used to differentiate between VaD and AD. We evaluated the
      expression of this receptor in the peripheral blood mononuclear cells of patients
      with VaD, mild cognitive impairment, AD, and controls. We found statistically
      significant lower levels of A2AR mRNA in VaD compared to AD subjects. These data
      suggest that A2AR expression may help in the differential diagnosis between VaD
      and AD. 

PMID- 24321893
TI  - Dementia among elderly in Shanghai suburb: a rural community survey.
AB  - The number of elderly in the world is increasing rapidly, especially in China.
      The prevalence of dementia among elderly was investigated in a community of
      Sheshan town, located in the Southwest suburb of Shanghai, China. Face-to-face
      interviews were conducted to collect relevant information with prepared
      questionnaires. The Chinese version of the Mini-Mental Status Examination was
      used to screen subjects with cognitive impairment (CI). Physical examinations and
      neuropsychological assessments were carried out. Dementia and its major subtypes,
      Alzheimer's disease (AD) and vascular dementia (VaD), were diagnosed by senior
      neurologists according to relevant diagnostic criteria. In addition, magnetic
      resonance imaging and EEG (with P300) were performed for a number of cases with
      AD or VaD. There were 1,472 participants (666 males and 806 females) aged 60
      years and over in the study. A total of 167 subjects with CI were screened. Among
      them, dementia was recognized in 79 cases with a prevalence of 5.37% (95%
      confidence intervals: 4.22%-6.52%). The diagnosis of AD was made for 53 cases (16
      males and 37 females) with a prevalence of 3.60% (95% confidence intervals: 2.65%
      4.55%), and VaD for 21 cases (5 males and 16 females) with a prevalence of 1.43%
      (95% confidence intervals: 0.82%-2.03%); while the ratio of AD to VaD was 2.52.
      The prevalence rates of dementia among elderly from our study are higher than
      that previously reported from China, but in line with that reported from most
      world regions. A nationwide survey and surveillance system on the prevalence of
      dementia is recommended.

PMID- 24321894
TI  - Contextual moderators of momentary cortisol and negative affect in adolescents'
      daily lives.
AB  - PURPOSE: To use an ecological momentary assessment design to examine the links
      between momentary negative affect and cortisol in a sample of adolescents
      preparing to transition to college. Guided by a risk and resilience framework, we
      also explored whether important ecological factors, perceived discrimination and
      social support, moderated the momentary associations between negative affect and
      youths' cortisol. METHODS: Adolescents (N = 77) provided salivary samples and
      diary reports of affect and experiences five times a day over 3 days. They also
      completed self-report questionnaires on perceived discrimination and social
      support from family and friends. RESULTS: Within-person increases in momentary
      negative affect were associated with increases in cortisol. Perceived
      discrimination and social support from friends moderated this association.
      Adolescents who reported average and high levels of perceived discrimination
      experienced exaggerated cortisol responses to negative affect, whereas
      adolescents who reported low levels of perceived discrimination did not
      experience significant reactivity to negative affect. In contrast, adolescents
      who reported high levels of social support from friends experienced attenuated
      cortisol responses to negative affect compared with adolescents who reported
      average or low levels of social support from friends. CONCLUSIONS: This study
      contributes to our understanding of youths' daily socioemotional experiences and
      physiological reactivity by identifying how perceived discrimination and social
      support from friends amplified and attenuated, respectively, the effects of
      negative affect on cortisol reactivity. Examining these processes within
      adolescents' naturalistic environments advances our understanding of the
      moderating role of ecological characteristics in adolescents' everyday lives.

PMID- 24321895
TI  - Continuous venovenous hemofiltration after coronary procedures for the prevention
      of contrast-induced acute kidney injury in patients with severe chronic renal
      failure.
AB  - Continuous venovenous hemofiltration (CVVH) is a renal replacement therapy that
      has been successfully used in patients with severe chronic renal failure to
      prevent contrast-induced acute kidney injury (CI-AKI). In this study, we present
      a consecutive experience using a new CVVH protocol that has also been applied to
      patients with acute coronary syndrome (ACS). CVVH was performed in consecutive
      patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2) (mean +/-
      SD, 21.1 +/- 7.3 ml/min/1.73 m(2)) undergoing diagnostic or interventional
      coronary procedures starting after the angiographic procedures. Iopamidol was
      used as a contrast agent. In the first 6 patients, iopamidol removal by the CVVH
      hemofilter and kidney was calculated by measuring iopamidol concentrations in the
      blood, urine, and ultrafiltrate collected during the 6-hour CVVH session. In the
      second phase, the protocol was applied to 47 additional patients meeting the
      inclusion criteria. Six-hour CVVH resulted in iopamidol removal comparable with
      that of 12-hour diuresis (43 +/- 12% vs 42 +/- 15% of administered, p = NS). CI
      AKI occurred in 7.5% of patients in the whole population and no patients had
      acute pulmonary edema, need for dialysis, or any major bleeding. In conclusion,
      in a population including patients with ACS with severe chronic renal failure
      undergoing coronary angiographic procedures, 6-hour CVVH performed only after
      contrast medium exposure was able to remove an amount of contrast medium similar
      to that removed by the kidneys in 12 hours and resulted in a low rate of CI-AKI.

PMID- 24321896
TI  - Effect of genetic polymorphisms of vascular endothelial growth factor on left
      ventricular hypertrophy in patients with systemic hypertension.
AB  - Vascular endothelial growth factor (VEGF) is a cytokine involved in angiogenesis
      and upregulated during adaptive heart hypertrophy. Downregulation of VEGF seems
      to trigger the transition from adaptive to dilated cardiac hypertrophy. We
      investigated for the first time whether 3 clinically relevant polymorphisms in
      the VEGFA gene are associated with altered echocardiographic parameters in
      hypertensive patients. We determined genotypes for 3 polymorphisms in VEGFA
      promoter in 179 hypertensive patients and 169 healthy controls: g.-2578C>A
      (rs699947), g.-1154G>A (rs1570360), and g.-634G>C (rs2010963). Although the
      variant genotypes of the g.-634G>C (GC + CC) were associated with reduced left
      ventricular mass index (p = 0.030), the variant genotypes for the g.-1154G>A (GA
      + AA) were associated with reduced ejection fraction (p = 0.008). In addition, we
      found that VEGFA haplotypes were associated with altered ejection fraction (p =
      0.024). The AAG haplotype was associated with reduced ejection fraction (p =
      0.006), whereas the AGG haplotype was associated with increased ejection fraction
      (p = 0.010). Our results suggest that VEGF polymorphisms affect cardiac
      remodeling. Genotypes for VEGFA polymorphisms can be useful to help to identify
      hypertensive patients at greater intrinsic risk for heart failure.

PMID- 24321897
TI  - Usefulness of pharmacologic conversion of atrial fibrillation during dofetilide
      loading without the need for electrical cardioversion to predict durable response
      to therapy.
AB  - Conversion of persistent atrial fibrillation (AF) to sinus rhythm is frequently
      seen during the 3-day in-hospital loading period required during dofetilide
      initiation, but it is not known whether pharmacologic conversion (PC) without the
      need for electrical cardioversion (EC) is a predictor of long-term maintenance of
      sinus rhythm during continued therapy with dofetilide. We sought to test the
      hypothesis that PC predicts durable maintenance of sinus rhythm and determine
      additional predictors of long-term maintenance of sinus rhythm on dofetilide. We
      retrospectively reviewed all elective inpatient admissions for dofetilide loading
      from 2003 to 2011 at the University of Virginia. A multivariate Cox proportional
      hazards model was used to assess predictors of maintenance of sinus rhythm after
      in-hospital dofetilide loading. In all, 101 patients with a current duration of
      AF lasting for a median of 1.86 months (interquartile range 0.47 to 6.03) were
      included in the analysis. Forty-seven patients were in the PC group, whereas 54
      patients were in the EC group. Patients in the PC group remained longer in sinus
      rhythm compared with the patients in the EC group (log-rank p = 0.032). The
      seventy-fifth percentile for the current episode duration in the PC group was
      5.77 months, indicating that even long-standing persistent AF frequently
      converted pharmacologically. Hypertension and a longer duration of the current AF
      episode were also predictors of recurrence in the multivariate model. In
      conclusion, PC during in-hospital dofetilide loading is an important predictor of
      durable response even in long-standing persistent patients, which has important
      public health implications for choice of therapy.

PMID- 24321898
TI  - Cause and effects of decreasing coronary revascularization procedures in
      California hospitals, 2006 to 2010.
AB  - Coronary revascularization procedures decreased markedly in California after the
      introduction of drug-eluting stents and the initiation of public reporting in
      2003, resulting in a large number of low-volume heart programs. California
      hospital discharge data were analyzed from 2006 to 2010 to study the impact of
      this change. In-hospital mortality and hospital readmission for major adverse
      events at 90 days and 365 days were determined for patients who underwent
      isolated coronary artery bypass grafting (CABG) or percutaneous coronary
      intervention (PCI) either with acute coronary syndrome (ACS) or PCI without acute
      coronary syndrome (PCI-noACS). Three terciles were chosen by case volume as
      follows: high-volume (747 +/- 336 [SD]/yr total PCI, 210 +/- 130 isolated CABG),
      intermediate volume (362 +/- 47 PCI, 106 +/- 27 CABG), and low-volume (211 +/- 6
      PCI, 53 +/- 17 CABG) terciles were studied. PCI-noACS procedures decreased 33%
      and CABG 20%, whereas PCI-ACS procedures increased slightly. Risk-adjusted in
      hospital mortality was slightly better in high-volume compared with low-volume
      terciles for CABG (2.0% vs 2.6%) and PCI-noACS (0.64% vs 0.85%). There was no
      difference in major adverse events at 90 days or 365 days among volume terciles
      within procedure groups, and no change in event rates was noted over the 5-year
      period. Wide variation in outcomes, associated with low volume, contributed to
      poor statistical discrimination among providers. In conclusion, lower volume
      hospitals had similar overall outcomes with wider variation. Conservative
      treatment strategies apparently contributed to decreased procedure volume.
      Collaboration among hospitals of similar structure and case volume may be the
      most appropriate performance improvement model to reduce variability among
      providers. 

PMID- 24321899
TI  - High-quality crystallinity controlled ALD TiO2 for waveguiding applications.
AB  - We demonstrate a novel atomic layer deposition (ALD) process to make high-quality
      nanocrystalline titanium dioxide (TiO(2)) with intermediate Al(2)O(3) layers to
      limit the crystal size. The process is based on titanium chloride (TiCl(4))+water
      and trimethyl aluminum (TMA)+ozone processes at 250 degrees C deposition
      temperature. The waveguide losses measured using a prism coupling method for 633
      and 1551 nm wavelengths are as low as 0.2+/-0.1 dB/mm with the smallest crystal
      size, with losses increasing with crystal size. In comparison, plain TiO(2)
      deposited at 250 degrees C without the intermediate Al(2)O(3) layers shows high
      scattering losses and is not viable as waveguide material. The third-order
      optical nonlinearity decreases with smaller crystal size as verified by third
      harmonic generation microscopy but still remains high for all samples.
      Crystallinity controlled ALD-grown TiO(2) is an excellent candidate for various
      optical applications, where good thermal stability and high third-order optical
      nonlinearity are needed.

PMID- 24321900
TI  - On the capacity of M-distributed atmospheric optical channels.
AB  - In this Letter, closed-form expressions of ergodic capacity, outage probability,
      and outage rate are derived for an atmospheric optical communication link using
      intensity modulation and direct detection with unbounded optical wavefront
      propagating through a homogeneous and isotropic turbulent medium. The optical
      scintillation of the received signal is modeled with the recently proposed Malaga
      or M turbulence distribution. By taking advantage of this unifying statistical
      model, the expressions here presented are valid for all possible irradiance
      fluctuation conditions, leading to direct relationships between turbulence
      parameters and link capacity performance. 

PMID- 24321901
TI  - Activation effect of Ho3+ at 2.84 MUm MIR luminescence by Yb3+ ions in GGG
      crystal.
AB  - The use of Yb(3+) co-doping for the enhancement of Ho(3+):(5)I(6)->(5)I(7) mid-IR
      (MIR) emissions was investigated in GGG crystal for the first time. It is
      established that Yb(3+) highly increases Ho(3+) 2.84 MUm emissions by
      transforming pump energy from the Yb(3+):(2)F(5/2) level to the laser upper level
      (5)I(6) of Ho(3+). The energy-transfer efficiency from Yb(3+):(2)F(5/2) to
      Ho(3+):(5)I(6) is calculated to be 96.2%. The absorption cross section, emission
      cross section, and fluorescence quantum efficiency are estimated and discussed.
      It is concluded that the Yb, Ho:GGG crystal is promising material for an LD
      pumped 2.84 MUm laser application.

PMID- 24321902
TI  - Miniaturized tunable imaging system inspired by the human eye.
AB  - We demonstrate the combination of a tunable lens and tunable aperture in a
      compact imaging system whose structure is inspired by the human eye. The concept
      is based on innovative optical materials and tuning mechanisms including an
      optofluidic iris for a tunable aperture and an elastomer lens for focal length
      tuning. Wavefront and modulation transfer function analysis reveals a high
      imaging performance of both the individual elements and the complete system. Most
      significantly, the wavefront is not degraded (DeltaPV<lambda/10) when tuning the
      focal length (Deltaf=5.36%). 

PMID- 24321903
TI  - Potential energy profile of colloidal nanoparticles in optical confinement.
AB  - An optical bottle method is developed to determine the potential-energy profile
      of colloidal Rayleigh nanoparticles in an optical trap. The three-dimensional
      distribution of fluorescent particles in the trap is measured by laser scanning
      confocal fluorescence microscopy. At sufficiently low concentrations at which
      interactions between the particles are negligible, the single-particle trapping
      potential-energy profile is determined from the equilibrium number-density
      profile by use of the Boltzmann distribution. Fluorescence imaging as well as
      calculations based on a discrete dipole approximation show that effects due to
      scattering forces are negligible for polystyrene particles of size less than 10%
      of the wavelength of the trapping laser, thus justifying the assumption of
      conservative forces in the equilibrium potential-energy determinations. The new
      optical bottle method measures the entire two-dimensional trapping-potential
      profile for an individual nanoparticle without the restriction that only one
      particle be contained in the trap, thus obviating the need for high laser power. 

PMID- 24321904
TI  - Optical fiber magnetic field sensor based on single-mode-multimode-single-mode
      structure and magnetic fluid.
AB  - An optical fiber magnetic field sensor based on the single-mode-multimode-single
      mode (SMS) structure and magnetic fluid (MF) is proposed and demonstrated. By
      using a piece of no-core fiber as the multimode waveguide in the SMS structure
      and MF sealed in a capillary tube as the magnetic sensitive media, which totally
      immersing the no-core fiber, an all-fiber magnetic sensor was fabricated.
      Interrogation of the magnetic field strength can be achieved either by measuring
      the dip wavelength shift of the transmission spectrum or by detecting the
      transmission loss at a specific wavelength. A demonstration sensor with
      sensitivities up to 905 pm/mT and 0.748 dB/mT was fabricated and investigated. A
      theoretical model for the design of the proposed device was developed and
      numerical simulations were performed.

PMID- 24321905
TI  - Uniformly spaced lambda/4-shifted Bragg grating array with wafer-scale CMOS
      compatible process.
AB  - We report on an integrated lambda/4-shifted Bragg grating array using a wafer
      scale complementary metal-oxide semiconductor (CMOS) compatible process with
      silicon-nitride waveguides. A sidewall grating was used to simplify the
      fabrication process, and a sampled Bragg grating with equivalent phase-shift
      structure was employed to achieve an accurate lambda/4 phase shift. A four
      channel lambda/4-shifted Bragg grating array with highly uniform channel spacing
      was demonstrated with a measured channel spacing variation below 10 pm (1.25
      GHz). The high channel-spacing uniformity and the CMOS-compatibility of the
      demonstrated device hold promise for integrated distributed feedback laser arrays
      for various silicon photonic applications. 

PMID- 24321906
TI  - 1.32 MUm mode-locked bismuth-doped fiber laser operating in anomalous and normal
      dispersion regimes.
AB  - We demonstrate a 1.32 MUm mode-locked bismuth fiber laser operating in both
      anomalous and normal dispersion regimes. In anomalous dispersion regime, achieved
      by using 13 nm/cm linearly chirped fiber Bragg grating, the laser exhibits
      multiple soliton operation with pulse duration of 2.51 ps. With the net normal
      cavity dispersion, the single-pulse operation with higher power has been obtained
      by avoiding the limitations generic to conservative soliton systems.

PMID- 24321907
TI  - High-brightness fiber laser-pumped 68 fs-2.3 W Kerr-lens mode-locked Yb:CaF2
      oscillator.
AB  - By using a high-brightness fiber pump laser, we demonstrate a pure Kerr-lens mode
      locked (ML) Yb:CaF(2) oscillator. The laser delivers 68 fs pulses with 2.3 W
      average power at 73 MHz repetition rate and an optical-to-optical efficiency of
      33% is achieved. To the best of our knowledge, this is the first demonstration of
      Kerr-lens mode-locking in Yb:CaF(2). Incidentally, we report here the highest
      average power ever achieved for a sub-100-fs active Kerr-lens ML Yb-bulk
      oscillator.

PMID- 24321908
TI  - Wavefront improvement in an injection-seeded soft x-ray laser based on a solid
      target plasma amplifier.
AB  - The wavefront of an injection-seeded soft x-ray laser beam generated by
      amplification of high-harmonic pulses in a lambda=18.9 nm molybdenum plasma
      amplifier was measured by a Hartmann wavefront sensor with an accuracy of
      lambda/32 root mean square (rms). A significant improvement in wavefront
      aberrations of 0.51+/-0.03lambda rms to 0.23+/-0.01lambda rms was observed as a
      function of plasma column length. The variation of wavefront characteristic as a
      function time delay between the injection of the seed and peak of soft x-ray
      amplifier pump was studied. The measurements were used to reconstruct the soft x
      ray source and confirm its high peak brightness.

PMID- 24321909
TI  - Accurate measurement of out-of-plane particle displacement from the cross
      correlation of sequential digital in-line holograms.
AB  - A new method to quantify three-dimensional particle fields using digital in-line
      holography is presented. From sequentially recorded holograms, the maximum cross
      correlation of edge sharpness within local particle windows yields an accurate
      measurement of particle displacements. Experiments demonstrate out-of-plane
      displacement uncertainty of approximately 0.15 mean particle diameters, which is
      roughly an order-of-magnitude improvement compared with alternative methods.
      Application to shotgun pellets demonstrates robustness despite experimental
      noise. 

PMID- 24321910
TI  - Fiber in-line Mach-Zehnder interferometer based on near-elliptical core photonic
      crystal fiber for temperature and strain sensing.
AB  - A fiber in-line Mach-Zehnder interferometer is fabricated by selectively filling
      liquid into one air hole of the innermost layer of a photonic crystal fiber
      (PCF). The refractive index of the liquid is so close to that of the background
      silica in the wavelength range of 1300-1600 nm that the two-mode PCF evolves into
      multimode PCF with an elliptically shaped core. Due to the different propagation
      constants, interference can occur between the fundamental mode and higher-order
      modes of the liquid-filled PCF. Such a device is applied in temperature and
      strain measurements with high sensitivities of 16.49 nm/ degrees C and -14.595
      nm/N, respectively.

PMID- 24321911
TI  - Diffraction of radiation of any state of spatial coherence on media with periodic
      structure.
AB  - A general formula is derived for the spectral density distribution in the far
      zone, produced by the diffraction of a beam of any state of spatial coherence on
      a medium with a spatially periodic structure. The formula may be used to
      determine the structure of crystals from the diffraction of partially coherent x
      ray beams. 

PMID- 24321912
TI  - Spectral characterization of laser-driven solid-based high harmonics in the
      coherent wake emission regime.
AB  - Laser-produced surface high-harmonic generation is an attractive source of
      extreme ultraviolet radiation due to its coherent properties and high peak power.
      By operating at subrelativistic laser intensities in the coherent wake emission
      regime, the harmonic spectrum was experimentally studied versus laser properties.
      At higher laser intensities (>10(17) W/cm(2)) a higher spectral cutoff was
      observed, with accompanying blueshifting and spectral broadening of the
      individual orders. A model based on an expanding critical surface provides
      qualitative agreement with the observations.

PMID- 24321913
TI  - Hot-wire polysilicon waveguides with low deposition temperature.
AB  - We fabricated and measured the optical loss of polysilicon waveguides deposited
      using hot-wire chemical vapor deposition at a temperature of 240 degrees C. A
      polysilicon film 220 nm thick was deposited on top of a 2000 nm thick plasma
      enhanced chemical vapor deposition silicon dioxide layer. The crystalline volume
      fraction of the polysilicon film was measured by Raman spectroscopy to be 91%.
      The optical propagation losses of 400, 500, and 600 nm waveguides were measured
      to be 16.9, 15.9, and 13.5 dB/cm, respectively, for transverse electric mode at
      the wavelength of 1550 nm. Scattering loss is expected to be the major
      contributor to the propagation loss.

PMID- 24321914
TI  - Tunable nonlinear parity-time-symmetric defect modes with an atomic cell.
AB  - We propose a scheme of creating a tunable highly nonlinear defect in a one
      dimensional photonic crystal. The defect consists of an atomic cell filled in
      with two isotopes of three-level atoms. The probe-field refractive index of the
      defect can be made parity-time (PT) symmetric, which is achieved by proper
      combination of a control field and of Stark shifts induced by a far-off-resonance
      field. In the PT-symmetric system, families of stable nonlinear defect modes can
      be formed by the probe field. 

PMID- 24321915
TI  - Design principle of Au grating couplers for quantum-well infrared photodetectors.
AB  - Based on analytic formulas and numerical simulations, we investigate the
      enhancement effect of Au gratings with spoof plasmon resonances on quantum-well
      infrared photodetectors (QWIPs) operating between 2 and 30 MUm. It is found that
      a simple analytic formula can well estimate the resonant wavelengths of Au
      gratings. Using optimal grating parameters, the absorption in the QW active
      region can be enhanced by 4-5 times compared with that in the reference structure
      (without gratings and with an isotropic active region). For s-polarized light, a
      high enhancement (>1.4) can occur in a broad range of incident angle (|theta|<40
      degrees ). 

PMID- 24321916
TI  - Possible mechanisms of switching in symmetrical two-ports based on 2D photonic
      crystals with magneto-optical resonators.
AB  - We analyze possible mechanisms of switching in two-ports based on 2D photonic
      crystals (PhCs) with a magneto-optical resonator. The input and output waveguides
      can be side or front coupled with the resonator. The resonator operates with a
      dipole mode. In the switch with front coupling in the nonmagnetic state the
      standing dipole mode provides equal nonzero wave amplitudes in the input and
      output waveguides and therefore transmission of the signal from the input to
      output waveguides. This is the state on. The applied magnetic field normal to the
      plane of the PhC rotates the standing dipole mode by 90 degrees  setting the
      nodes in the input and output waveguides. This corresponds to the state off. On
      the contrary, in the switch with side coupling and nonmagnetized resonator, the
      standing dipole mode excited by a wave in the input waveguide has its node in the
      output waveguide. Therefore, the signal is reflected from the input port. This
      corresponds to the state off of the switch. Magnetization by a DC magnetic field
      produces a rotating dipole pattern in the cavity. Due to this rotating, the mode
      signal passes from the input port to the output one and this is the state on. 

PMID- 24321917
TI  - Asymmetric cryptosystem using random binary phase modulation based on mixture
      retrieval type of Yang-Gu algorithm: comment.
AB  - We comment on the recent Letter, by Liu et al. [Opt. Lett.38, 1651 (2013)] in
      which a method to improve the security strength of the asymmetric cryptosystem
      (ACS) by Qin and Peng [Opt. Lett.35, 118 (2010)] was proposed. However, in
      accordance with Liu's methodology, we could easily find other more efficient ways
      to achieve their purpose. More importantly, we think it is vitally necessary to
      point out that there exists a widespread, fundamental misunderstanding on the
      concept of ACS, which has also been studied in a series of related works. 

PMID- 24321918
TI  - Asymmetric cryptosystem using random binary phase modulation based on mixture
      retrieval type of Yang-Gu algorithm: reply.
AB  - We appreciate the comment by He et al. [Opt. Lett.38, 4044 (2013)] in the sense
      that it allows us to clarify our methodology of constructing an optical
      asymmetric cryptosystem, especially the relationship of the public encryption
      keys and private decryption keys. We also take this opportunity to provide a more
      detailed discussion to promote the research about the optical encryption schemes
      with asymmetric keys into a more correct direction. 

PMID- 24321919
TI  - Tunable optical parametric amplification of a single-frequency quantum cascade
      laser around 8 MUm in ZnGeP2.
AB  - We demonstrate optical parametric amplification in ZnGeP(2) (ZGP) of the
      radiation emitted by a single-frequency continuous-wave quantum cascade laser
      (QCL) in the range 7.8-8.4 MUm. The ZGP amplifier is pumped by a single-frequency
      parametric source at 2210 nm. For a pump energy of 6 mJ, we report an average
      gain of 50 over this range and a maximum gain of 111 for 7.5 mJ. An exponential
      trend is observed when changing the pump energy, with very good agreement with
      theory. These features are of valuable interest for increasing the standoff
      detection range of hazardous chemicals and explosives by QCL-based backscattering
      spectroscopy systems.

PMID- 24321920
TI  - Photonic band gaps induced by submicron acoustic plate waves in dielectric slab
      waveguides.
AB  - We generate photonic bandgaps (PBGs) in dielectric slab waveguides by exciting
      their acoustic plate eigenmodes of submicron wavelength. We investigate the
      optical forbidden bands below the light line where the slab interfaces and index
      of refraction are periodically modulated by the acoustic fields. Results show
      that multiple scattering through the enhanced periodic acousto-optic (AO)
      interaction opens Bragg PBGs. A tunable bandgap width and transmittance are
      achieved. Transmitted optical waves are found to incur strong nonlinear
      modulation through AO interaction by a multiphonon exchange mechanism. The
      applications include tunable optomechanical and AO devices. 

PMID- 24321921
TI  - Experimental demonstration of an integrated hybrid plasmonic polarization
      rotator.
AB  - We experimentally demonstrate an ultracompact (3.7 MUm long) hybrid plasmonic
      polarization rotator operating around 1.55 MUm for integrated silicon photonics
      circuits. The TM polarization of a silicon waveguide is rotated to the TE
      polarization with insertion losses as low as 1.5 dB and polarization extinction
      ratios larger than 13.5 dB.

PMID- 24321922
TI  - Three-dimensional imaging using continuously self-imaging gratings.
AB  - In this Letter, we propose a method to perform 3D imaging with a simple and
      robust imaging system only composed of a continuously self-imaging grating (CSIG)
      and a matrix detector. With a CSIG, the intensity pattern generated by an object
      source is periodic and propagation invariant, apart from a dilatation factor that
      depends on the distance of the object. We demonstrate, theoretically and
      experimentally, how to exploit this property to analyze a scene in three
      dimensions. Such an imaging system can be used, for example, for tomographic
      applications. 

PMID- 24321923
TI  - Atmospheric turbulence effects on the performance of a free space optical link
      employing orbital angular momentum multiplexing.
AB  - We experimentally investigate the performance of an orbital angular momentum
      (OAM) multiplexed free space optical (FSO) communication link through emulated
      atmospheric turbulence. The turbulence effects on the crosstalk and system power
      penalty of the FSO link are characterized. The experimental results show that the
      power of the transmitted OAM mode will tend to spread uniformly onto the
      neighboring mode in medium-to-strong turbulence, resulting in severe crosstalk at
      the receiver. The power penalty is found to exceed 10 dB in a weak-to-medium
      turbulence condition due to the turbulence-induced crosstalk and power
      fluctuation of the received signal. 

PMID- 24321924
TI  - Coherent total internal reflection dark-field microscopy: label-free imaging
      beyond the diffraction limit.
AB  - Coherent imaging is barely applicable in life-science microscopy due to multiple
      interference artifacts. Here, we show how these interferences can be used to
      improve image resolution and contrast. We present a dark-field microscopy
      technique with evanescent illumination via total internal reflection that
      delivers high-contrast images of coherently scattering samples. By incoherent
      averaging of multiple coherent images illuminated from different directions we
      can resolve image structures that remain unresolved by conventional (incoherent)
      fluorescence microscopy. We provide images of 190 nm beads revealing resolution
      beyond the diffraction limit and slightly increased object distances. An
      analytical model is introduced that accounts for the observed effects and which
      is confirmed by numerical simulations. Our approach may be a route to fast, label
      free, super-resolution imaging in live-cell microscopy. 

PMID- 24321925
TI  - Simultaneous measurement of curvature and strain based on fiber Bragg grating in
      two-dimensional waveguide array fiber.
AB  - We report on the fabrication of a fiber Bragg grating (FBG) with multiple
      resonances in a two-dimensional waveguide array microstructured optical fiber
      containing 91 cores. Theoretical investigation reveals that these resonances
      originate from the identical and nonidentical mode couplings between forward
      propagating and backward-propagating LP<sub>0m</sub>-like (m=1, 2, 3; LP refers
      to linearly polarized) supermodes. Since both the central wavelength and minimum
      transmission of these resonant dips respond differently to curvature and axial
      strain, this FBG can be applied in the simultaneous measurement of curvature and
      axial strain. 

PMID- 24321926
TI  - Sensitivity enhancement in high resolution stimulated Raman spectroscopy of gases
      with hollow-core photonic crystal fibers.
AB  - We show the first experimental evidence of the sensitivity enhancement that can
      be achieved in high resolution stimulated Raman spectroscopy of gases using
      hollow-core photonic crystal fibers (HCPCFs). Using low power cw lasers and a
      HCPCF containing the gas, we have observed more than four orders of magnitude
      enhancement of sensitivity when compared with the cw single focus regime, and a
      similar sensitivity to that achieved in the more sensitive quasi-cw setups with
      multipass cells. 

PMID- 24321927
TI  - Quantum entanglement in plasmonic waveguides with near-zero mode indices.
AB  - We investigate the quantum entanglement between two quantum dots (QDs) in a
      plasmonic waveguide with a near-zero mode index, considering the dependence of
      concurrence on interdot distance, QD waveguide frequency detuning, and coupling
      strength ratio. High concurrence is achieved for a wide range of interdot
      distances due to the near-zero mode index, which largely relaxes the strict
      requirement of interdot distance in conventional dielectric waveguides or metal
      nanowires. The proposed QD waveguide system with near-zero phase variation along
      the waveguide near the mode cutoff frequency shows very promising potential in
      quantum optics and quantum information processing. 

PMID- 24321928
TI  - Highly bright broadband red light produced by fluorescence polymer/InGaN hybrid
      light-emitting diodes.
AB  - The fabrication of fluorescence polymer/InGaN hybrid light-emitting diodes (LEDs)
      that emit highly bright broadband red light is presented in this Letter. The
      absorption peak of the fluorescence polymer was 455 nm, and the emission peak was
      640 nm. The light output power and external quantum efficiency of hybrid LEDs at
      a driving current of 100 mA were 46.6 mW and 24.1%, respectively. The emission
      spectrum of hybrid LEDs was located at a wavelength of 641 nm, with a broadband
      FWHM of 106 nm. Thus this study offers potential methods for enhancing the output
      power of commercial white-light-emitting devices. 

PMID- 24321929
TI  - Ultrahigh-order mode-assisted determination of enantiomeric excess in chiral
      liquids.
AB  - A chiral liquid, whose constituent molecules lack mirror symmetry, exhibits a
      minor differential refractive index (RI) between the two circular polarization
      components. Theoretical analysis shows that the ultrahigh-order modes excited in
      a symmetrical metal-cladding waveguide (SMCW) are polarization-independent and
      have a highly sensitive response to the RI variation. We report the observation
      of circular differential reflectivity in a chiral liquid-filled SMCW and propose
      an alternative simple technique capable of determining enantiomeric excess with
      high sensitivity. 

PMID- 24321930
TI  - Diode-side-pumped Nd:YLF laser emitting at 1313 nm based on DBMC technology.
AB  - Efficient lasers operating in the 1.3 MUm band are of interest in the health
      industry for frequency conversion to the visible spectral region and for Raman
      shifting to the eye-safe 1.5 MUm region. In this work, we demonstrate for the
      first time, to our knowledge, a side-pumped Nd:YLiF(4) laser emitting at 1.3 MUm.
      An output power of up to 14.9 W was obtained at 1313 nm with 54 W of absorbed
      pump power, representing 27.7% optical efficiency and a slope efficiency of 45%.

PMID- 24321931
TI  - All-optical bistable logic control based on coupled Tamm plasmons.
AB  - A method for realizing low-threshold all-optical bistable logic control is
      proposed based on Tamm plasmons (TPs), which are formed in an asymmetric
      dielectric Bragg reflector (DBR)-metal-DBR (ADMD) structure with a layer of Kerr
      medium embedded. The ADMD structure supports two TPs due to coupling of trapped
      modes at each metal-DBR interface, generating two dips in the structure's
      reflection spectrum. Thus, control (i.e., pump) and controlled (i.e., probe)
      light with wavelengths close to the two dips, respectively, can be imported. It
      is verified theoretically that, thanks to the enhanced Kerr nonlinearity related
      to excitation of high-quality TP, bistable switching at very low injection
      intensity can be initiated by strength or direction variation of the pump.
      Meanwhile, the probe changes correspondingly with the pump. Thus, all-optical
      bistable logic operation of the probe can be controlled by the pump. 

PMID- 24321932
TI  - Polarization sensitive camera by femtosecond laser nanostructuring.
AB  - A polarization imaging device based on a femtosecond laser nanostructured
      birefringent array is demonstrated. The device enables instant measurement of the
      distribution of the Stokes vectors in the visible spectrum. Polarimetric
      measurements with radially and circularly polarized light distributions are
      demonstrated. 

PMID- 24321933
TI  - Conical refraction as a tool for polarization metrology.
AB  - A method for polarization metrology based on the conical refraction (CR)
      phenomenon, occurring in biaxial crystals, is reported. CR transforms an input
      Gaussian beam into a light ring whose intensity distribution is linked to the
      incoming polarization. We present the design of a division-of-amplitude complete
      polarimeter composed of two biaxial crystals, whose measurement principle is
      based on the CR phenomenon. This design corresponds to a static polarimeter, that
      is, without mechanical movements or electrical signal addressing. Only one
      division-of-amplitude device is required, besides the two biaxial crystals, to
      completely characterize any state of polarization, including partially polarized
      and unpolarized states. In addition, a mathematical model describing the system
      is included. Experimental images of the intensity distribution related to
      different input polarization states are provided. These intensity patterns are
      compared with simulated values, proving the potential of polarimeters based on
      biaxial crystals. 

PMID- 24321934
TI  - Direct observation of Kramers-Kronig self-phasing in coherently combined fiber
      lasers.
AB  - A highly stable coherent beam-combining system has been designed to measure self
      phasing in fiber lasers due to nonlinear effects. Whereas self-phasing in
      previous coherent combination experiments has been principally attributed to
      wavelength shifting, these wavelength effects have been efficiently suppressed in
      our experiment by using a dual-core fiber with closely balanced optical path
      lengths. The self-phasing from nonlinear effects could then be measured
      independently and directly by common-path interferometry with a probe laser. The
      Kramers-Kronig effect in the fiber gain media was observed to induce a phase
      shift that effectively canceled the applied path length errors, resulting in
      efficient lasing under all phase conditions. This process was demonstrated to
      result in robust lasing over a large range of pump conditions. 

PMID- 24321935
TI  - Walsh modes and radial quantum correlations of spatially entangled photons.
AB  - Orthogonal sets of 2D transverse modes are key to controlling the spatial degree
      of freedom of light in a classical or quantum context. In contrast to the
      azimuthal part, which is easily accessible using orbital angular momentum modes,
      control of the radial part is more difficult. We show here that simple sets of
      orthogonal binary sequences, the Walsh functions, provide a workable solution for
      exploration of the radial space with phase-only spatial light modulation. We
      demonstrate this by measuring "sequency" quantum correlations between different
      radial Walsh modes of spatially entangled photon pairs and for numerically
      optimized versions thereof. 

PMID- 24321936
TI  - Time-resolved microscopy with random lasers.
AB  - We demonstrate that random lasers provide an outstanding strobe light source for
      time-resolved microscopy. Utilizing a random laser to illuminate a commercially
      available microscope enables single exposure, speckle-free time-resolved imaging.
      Aside from conventional optical transmission microscopy, we also perform time
      resolved investigations in phase contrast mode. We apply this method to the
      monitoring of fs-laser-induced microdot formation in bulk a-SIO(2). Time-resolved
      investigations show that microdot formation lasts over several microseconds after
      laser excitation.

PMID- 24321937
TI  - Low voltage tunable liquid crystal lens.
AB  - In this Letter, we report a method to prepare a liquid crystal (LC) lens based on
      a variable pretilt angle of a photoalignment (PA) layer. With precise control of
      the irradiance, such PA provides good control on the pretilt angle that can be
      tuned in the range of 1 degrees -89 degrees . Therefore, the precise control of
      the irradiance generates a spatially varying pretilt angle with any desired
      pretilt angle profile. Thus, the tunable LC lenses have been fabricated and
      characterized. With low voltage operations, easy fabrication, and relatively high
      switching speed, such lenses can be applied in many modern optical and photonic
      devices. 

PMID- 24321938
TI  - Development of a dual-path system for band-to-band registration of an acousto
      optic tunable filter-based imaging spectrometer.
AB  - Accurate band-to-band registration is crucial when an acousto-optic tunable
      filter (AOTF)-based imaging spectrometer is used to acquire spectral data on an
      unstable platform. However, it is difficult to registrate hyperspectral images
      accurately using traditional image registration algorithms, which will seriously
      affect the accurate acquisition of spectra and reduce the classification
      accuracy. Here we demonstrate an optical configuration that acquires the
      diffracted and undiffracted beam of the AOTF simultaneously. These two beams have
      identical geometrical optical characteristic and suffer from the same image
      motion caused by the platform jitter. Compared with the diffracted beam, however,
      the intensity of the undiffracted beam is changeless when tuning the AOTF.
      Therefore, the use of undiffracted beams allows accurate measurement of image
      motion in different bands. The experiment shows that this technique greatly
      improves the registration accuracy of spectral images with poor correlation and
      low SNR. 

PMID- 24321939
TI  - Enhancement strategy based on three-layer filtering for a single fringe pattern.
AB  - The quality enhancement of a single fringe pattern is a challenging task in
      speckle interferometry. Fringe patterns suffer greatly from three adverse
      variations (nonuniform background, speckle noise, and intensity modulation). In
      this Letter, we propose a three-layer filtering strategy for noisy fringe
      patterns. The first layer is aimed at high-frequency speckle noises and low
      frequency background. The second layer is for remaining speckle noises
      distributed in the middle-frequency band. The third layer will further implement
      quality enhancement by a phase-recovery technique. The proposed strategy is
      quantitatively evaluated by different indexes and verified to be effective
      through numerous comparative experiments. 

PMID- 24321940
TI  - Low-cost and wideband frequency tunable optoelectronic oscillator based on a
      directly modulated distributed feedback semiconductor laser.
AB  - A novel scheme to realize a low-cost and wideband frequency tunable
      optoelectronic oscillator based on a directly modulated distributed feedback
      (DFB) semiconductor laser is proposed and experimentally demonstrated. In the
      proposed scheme, neither an external modulator nor an electrical filter is used,
      and no more than 25 dB of the electrical loop gain is required due to the high
      modulation efficiency of the relaxation oscillation frequency of the DFB laser.
      Microwave signals with frequency coarsely tuned from 3.77 to 8.75 GHz are
      generated by changing the bias current and operation temperature of the DFB
      laser. The single sideband phase noise of the generated 6.97 GHz microwave signal
      is measured to be -103.6 dBc/Hz at 10 kHz offset.

PMID- 24321941
TI  - 28-W, 217 fs solid-state Yb:CAlGdO4 regenerative amplifiers.
AB  - A new high-performance Yb:CaAlGdO(4) (Yb:CALGO) regenerative amplifier is
      demonstrated. Pumped by 116 W at ~980 nm and seeded by means of a 92 fs
      oscillator, it generates as much as 36 W of average output power with chirped
      pulses, and 28 W with 217 fs compressed pulses at 500 kHz repetition rate. This
      corresponds to 56 MUJ of pulse energy and 258 MW peak power. The compressed
      pulses have a time-bandwidth product of 0.69 and could be shortened further with
      an improved compressor setup.

PMID- 24321942
TI  - Effects of persistent luminescence decay on mechanoluminescence phenomena of
      SrAl2O4:Eu2+, Dy3+ materials.
AB  - This Letter reveals for the first time, to the best of our knowledge, the effects
      of stress-free persistent luminescence (PL) decay on the mechanoluminescence (ML)
      phenomena and the effects of stresses and strain rates on the PL decay of
      SrAl(2)O(4):Eu(2+), Dy(3+) (SAOED) materials. Previous research on ML phenomena
      in this material has focused on the effects of strain rates and stress variations
      on ML light intensity. However, experimental evidence provided herein shows that
      the ML light emission is also related to the PL decay time elapsed until the
      onset of stressing and the PL decay rate is dependent on the stress, strain rate,
      and the stress-free PL decay time interval. For quantitative stress measurements
      using SAOED materials, understanding of ML light sensitivity and its dependence
      on critical factors (strain rate, stress-free PL decay time interval,
      photoexcitation time, instantaneous PL decay rate, etc.) is crucially important.
      This Letter provides new and important perspectives that are essential for
      developing predictive models and/or calibration procedures for ML stress sensors.

PMID- 24321943
TI  - Magic mode switching in Yb:CaGdAlO4 laser under high pump power.
AB  - We present unique spatial-mode switching in a cw Yb:CALGO laser when pumped at a
      multihundred-watts power level. It permits us to automatically stabilize to a
      TEM(00) mode from a highly spatial multimode regime. This stabilization is
      achievable thanks to polarization-mode switching allowed by the particular
      spectroscopic and thermal properties of Yb:CALGO crystal. This atypical and
      unexpected behavior is studied in detail in this Letter and explained by analysis
      of the thermo-optical coefficients for CALGO.

PMID- 24321944
TI  - Toward transduodenal diffuse optical tomography of proximal pancreas.
AB  - We demonstrate the feasibility of diffuse optical tomography (DOT) of the
      proximal pancreas by using optical applicator channels deployed longitudinally
      along the exterior surface of a duodenoscope. As the duodenum that nearly
      encircles the proximal pancreas forms a natural "C-loop" that is approximately
      three-quarters of a circle of 5-6 cm in diameter, a multichannel optical
      applicator attached to a duodenoscope has the potential to perform transduodenal
      DOT sampling of the bulk proximal pancreas wherein most cancers and many cystic
      lesions occur. The feasibility of transduodenal DOT is demonstrated on normal
      porcine pancreas tissues containing an introduced gelatinous inclusion of
      approximately 3 cm in diameter, by using nine source channels and six detector
      channels attached to a duodenoscope. Concurrent ultrasonography of the gelatinous
      inclusion in the porcine pancreas parenchyma provided a coarse, albeit
      indispensable, anatomic prior to transduodenal DOT in reconstructing a contrast
      of optical properties in the pancreas. 

PMID- 24321945
TI  - Laser demonstration with highly doped Yb:Gd2O3 and Yb:Y2O3 crystals grown by an
      original flux method.
AB  - We present, to the best of our knowledge, the first laser demonstration of an Yb
      doped Gd(2)O(3) cubic crystal. This crystal was obtained by the flux method using
      an original borate-based solvent, which was particularly well suited to the
      growth of rare earth sesquioxide crystals at half the working temperature of
      classical growth techniques. This flux method is a very interesting alternative
      for the production of laser sesquioxide crystals, not only because it provides
      access to new matrices of the cubic polymorph, but also because it permits high
      Yb(3+)-doping levels for these crystals. The first laser results of two highly
      Yb(3+)-doped sesquioxides, namely Gd(2)O(3) and Y(2)O(3), grown by this flux
      method are presented here, including the Ti:sapphire and diode pumping
      configurations. Laser efficiencies and emission spectra for these two crystals
      were studied and compared.

PMID- 24321946
TI  - High average power picosecond pulse and supercontinuum generation from a thulium
      doped, all-fiber amplifier.
AB  - We demonstrate a high-power, picosecond, thulium-doped, all-fiber master
      oscillator power amplifier with average power of 120.4 W. The compact fiber
      oscillator is carefully designed with high repetition rate for the purpose of
      overcoming the detrimental effects of fiber nonlinearity in the later fiber
      amplifiers. The pulse duration of 16 ps at 333.75 MHz repetition rate results in
      a peak power of 22.5 kW in the final fiber power amplifier. To the best of our
      knowledge, this is the first demonstration of average power exceeding 100 W from
      an ultrashort pulse laser at 2 MUm wavelength. On the other hand, by decreasing
      the fiber oscillator repetition rate and pulse duration for enhancing the fiber
      nonlinearity effects, we also demonstrate a high-power supercontinuum source with
      average power of 36 W from 1.95 MUm to beyond 2.4 MUm in the final fiber power
      amplifier. 

PMID- 24321947
TI  - Fiber optical parametric oscillator for coherent anti-Stokes Raman scattering
      microscopy.
AB  - We present a synchronously pumped fiber optical parametric oscillator for
      coherent anti-Stokes Raman scattering microscopy. Pulses from a 1 MUm Yb-doped
      fiber laser are amplified and frequency converted to 779-808 nm through normal
      dispersion four-wave mixing in a photonic crystal fiber. The idler frequency is
      resonant in the oscillator cavity, and we find that bandpass filtering the
      feedback is essential for stable, narrow-bandwidth output. Experimental results
      agree quite well with numerical simulations of the device. Transform-limited 2 ps
      pulses with energy up to 4 nJ can be generated at the signal wavelength. The
      average power is 180 mW, and the relative-intensity noise is much lower than that
      of a similar parametric amplifier. High-quality coherent Raman images of mouse
      tissues recorded with this source are presented. 

PMID- 24321948
TI  - Selective excitation of lowest-order transverse ring modes in a quasi-stadium
      laser diode.
AB  - For a two-dimensional quasi-stadium laser diode, we demonstrate stable excitation
      of the lowest-order transverse ring modes by optimally designing the confocal end
      mirrors of the laser cavity based on extended Fox-Li mode calculations. We
      observe kink-free light output versus injection current characteristics and
      highly directional single-peak emissions corresponding to the diamond-shaped
      trajectory in the cavity. These results provide convincing evidence for selective
      excitation of the lowest-order transverse modes. 

PMID- 24321949
TI  - Hybrid Raman/Brillouin-optical-time-domain-analysis-distributed optical fiber
      sensors based on cyclic pulse coding.
AB  - We experimentally demonstrate the use of cyclic pulse coding for distributed
      strain and temperature measurements in hybrid Raman/Brillouin optical time-domain
      analysis (BOTDA) optical fiber sensors. The highly integrated proposed solution
      effectively addresses the strain/temperature cross-sensitivity issue affecting
      standard BOTDA sensors, allowing for simultaneous meter-scale strain and
      temperature measurements over 10 km of standard single mode fiber using a single
      narrowband laser source only. 

PMID- 24321950
TI  - Integrated 1550 nm photoreceiver with built-in amplification and feedback
      mechanisms.
AB  - Sensitivity, dynamic range and detection efficiency are among the key figures of
      merit for 1550 nm wavelength detectors that find applications in communications,
      sensing, and imaging. Some fundamental material and device limits have added
      tremendous difficulties for a single device to achieve high sensitivity and
      dynamic range without significant trade-offs. We present a concept that can
      potentially overcome this performance bottleneck. Preliminary results have shown
      a sensitivity of 10 photons (six photons from the quantum limit) and a large
      dynamic range (in the sense that output increases monotonically with input). The
      concept opens up a new avenue for detecting single photons in non-Geiger-mode
      with near 100% detection efficiency. 

PMID- 24321951
TI  - Nanodiamonds with silicon vacancy defects for nontoxic photostable fluorescent
      labeling of neural precursor cells.
AB  - Nanodiamonds (NDs) containing silicon vacancy (SiV) defects were evaluated as a
      potential biomarker for the labeling and fluorescent imaging of neural precursor
      cells (NPCs). SiV-containing NDs were synthesized using chemical vapor deposition
      and silicon ion implantation. Spectrally, SiV-containing NDs exhibited extremely
      stable fluorescence and narrow bandwidth emission with an excellent signal to
      noise ratio exceeding that of NDs containing nitrogen-vacancy centers. NPCs
      labeled with NDs exhibited normal cell viability and proliferative properties
      consistent with biocompatibility. We conclude that SiV-containing NDs are a
      promising biomedical research tool for cellular labeling and optical imaging in
      stem cell research. 

PMID- 24321953
TI  - Fast thermal regeneration of fiber Bragg gratings.
AB  - In this Letter we report a fast thermal regeneration of Type I fiber Bragg
      gratings inscribed with a UV laser in up to four different optical fibers:
      hydrogenated standard fiber, hydrogenated highly Ge-doped fiber, hydrogenated
      photosensitive fiber, and nonhydrogenated fiber. The thermal treatment consists
      in directly introducing the optical fiber into a preheated oven. The preheat
      temperature depends on the type of fiber used and is high enough to erase the
      grating and regenerate it afterward. The best results are obtained with
      hydrogenated photosensitive fiber and highly Ge-doped fiber, whereas no
      satisfactory results were obtained with hydrogenated standard fiber and
      nonhydrogenated photosensitive fiber. A regenerated grating with only 1.6 dB of
      loss was obtained in 10 min, reducing the time needed by a factor of 5.7. By
      adjusting the temperature of the oven, regenerated gratings of 13.7 dB of loss in
      31 s and 5.8 dB of loss in 3 min were obtained. The factors of improvement in
      time are 110.3 and 19, respectively. 

PMID- 24321952
TI  - Coupled lasers: phase versus chaos synchronization.
AB  - The synchronization of chaotic lasers and the optical phase synchronization of
      light originating in multiple coupled lasers have both been extensively studied.
      However, the interplay between these two phenomena, especially at the network
      level, is unexplored. Here, we experimentally compare these phenomena by
      controlling the heterogeneity of the coupling delay times of two lasers. While
      chaotic lasers exhibit deterioration in synchronization as the time delay
      heterogeneity increases, phase synchronization is found to be independent of
      heterogeneity. The experimental results are found to be in agreement with
      numerical simulations for semiconductor lasers. 

PMID- 24321954
TI  - Low-haze light extraction from organic light-emitting diode lighting with
      auxiliary electrode by selective microlens arrays.
AB  - Improved out-coupling efficiency and low haze of organic light-emitting diode
      (OLED) lighting with an auxiliary electrode are demonstrated by selective
      microlens arrays (SMLAs). The microlens arrays, aligned with the auxiliary
      electrode, were selectively fabricated, since the fully packed microlens arrays
      lead to OLED lighting with high haze. The external quantum efficiency and power
      efficiency of the devices with the SMLAs increased by 32% when compared with the
      devices without these arrays. Using the SMLAs, dark grid lines in the emission
      region became brighter, with a low haze, and the spectra of the emitted light had
      no shift. 

PMID- 24321955
TI  - Digital signal processing based on inverse scattering transform.
AB  - Through numerical modeling, we illustrate the possibility of a new approach to
      digital signal processing in coherent optical communications based on the
      application of the so-called inverse scattering transform. Considering without
      loss of generality a fiber link with normal dispersion and quadrature phase shift
      keying signal modulation, we demonstrate how an initial information pattern can
      be recovered (without direct backward propagation) through the calculation of
      nonlinear spectral data of the received optical signal. 

PMID- 24321956
TI  - High-efficiency femtosecond Yb:Gd3Al(0.5)Ga(4.5)O12 mode-locked laser based on
      reduced graphene oxide.
AB  - A diode-pumped Yb-doped Gd(3)Al(0.5)Ga(4.5)O(12) mode-locked bulk laser based on
      chemically reduced graphene oxide (RGO) has been demonstrated for the first time
      to our best knowledge. Pulses with duration of 643 fs were produced at the
      central wavelength of 1041.1 nm. A maximum average output power of 0.8 W was
      obtained from the RGO mode-locked laser, corresponding to a slope efficiency of
      20.1% and a peak power of 27.6 kW. The results indicate that RGO is suitable for
      obtaining high-power and high-efficiency ultrafast lasers.

PMID- 24321957
TI  - Deep UV-induced near-infrared photodarkening of Er/Yb-doped and undoped phosphate
      fibers.
AB  - Photodarkening (PD) of Er/Yb-doped and undoped phosphate fibers caused by pulsed
      193 nm irradiation from an ArF excimer laser to form Bragg grating mirrors is
      investigated. Doped and undoped phosphate fibers exhibit the same level of
      significant UV-induced PD loss, which is associated with the formation of a color
      center band at 467 nm. The UV-induced absorption extends into the NIR and creates
      a loss on the order of 1 dB/cm across the C-band. Photo-bleaching by a high-power
      supercontinuum source, and thermal-bleaching processes are performed on
      photodarkened samples. Both bleaching processes are found effective to fully
      erase the UV-induced PD loss.

PMID- 24321958
TI  - Telecom technology based continuous wave terahertz photomixing system with 105
      decibel signal-to-noise ratio and 3.5 terahertz bandwidth.
AB  - A modified photoconductive receiver significantly improves the performance of
      photomixing-based continuous wave (cw) THz systems driven at the optical
      telecommunication wavelength of 1.5 MUm. The achieved signal-to-noise ratio of
      105 dB at 100 GHz and 70 dB at 1 THz, both for an integration time of 200 ms, are
      to our knowledge the highest numbers reported in literature for any
      optoelectronic cw THz system, including classical setups operating at 800 nm. The
      developed receiver allows for combining low cost and high performance in one
      system for the first time to our knowledge. 

PMID- 24321959
TI  - Light trapping and near-unity solar absorption in a three-dimensional photonic
      crystal.
AB  - We report what is to our knowledge the first observation of the effect of
      parallel-to-interface-refraction (PIR) in a three-dimensional, simple-cubic
      photonic-crystal. PIR is an acutely negative refraction of light inside a
      photonic-crystal, leading to light-bending by nearly 90 deg over broad
      wavelengths (lambda). The consequence is a longer path length of light in the
      medium and an improved light absorption beyond the Lambertian limit. As an
      illustration of the effect, we show near-unity total absorption (>=98%) in
      lambda=520-620 nm and an average absorption of ~94% over lambda=400-700 nm for
      our alpha-Si:H photonic-crystal sample of an equivalent bulk thickness of t~=450
      nm. Furthermore, we have achieved an ultra-wide angular acceptance of light over
      theta=0 degrees -80 degrees . This demonstration opens up a new door for light
      trapping and near-unity solar absorption over broad lambdas and wide angles.

PMID- 24321960
TI  - High-order harmonic generation from a dual-gas, multi-jet array with individual
      gas jet control.
AB  - We present a gas jet array for use in high-order harmonic generation experiments.
      Precise control of the pressure in each individual gas jet has allowed a thorough
      investigation into mechanisms contributing to the selective enhancement observed
      in the harmonic spectra produced by dual-gas, multi-jet arrays. Our results
      reveal that in our case, the dominant enhancement mechanism is the result of a
      compression of the harmonic-producing gas jet due to the presence of other gas
      jets in the array. The individual control of the gas jets in the array also
      provides a promising method for enhancing the harmonic yield by precise tailoring
      of the length and pressure gradient of the interaction region. 

PMID- 24321961
TI  - Formation of polarized beams in chains of dielectric spheres and cylinders.
AB  - Using numerical modeling, it is shown that chains of dielectric spheres and
      cylinders act as polarizers. The mechanism is based on gradual filtering of
      periodically focused modes with a certain polarization propagating with minimal
      losses due to Brewster angles conditions, whereas orthogonally polarized modes
      are strongly attenuated. It is shown that chains of cylinders filter linearly
      polarized beams, whereas chains of spheres filter radially polarized beams. In
      the geometrical optics limit, we show that in a range of sphere refractive
      indices 1.68-1.80 a degree of radial polarization in excess of 0.9 can be
      obtained in 10-sphere-long chains. 

PMID- 24321962
TI  - Direct laser writing of buried waveguide in As2S3 glass using a helical sample
      translation.
AB  - We report the fabrication and the characterization of buried waveguide in
      As(2)S(3) glass. It is well known that the interaction of femtosecond pulses with
      this material at high laser repetition rates results in a mainly negative
      refractive index variation, due to heat accumulation effect. However, we show
      here that a helical translation of the sample parallel to the laser beam, allows
      the inscription of a core of positive refractive variation, with full control
      over its magnitude and diameter. An example demonstrating the high symmetry of
      the guided mode is given.

PMID- 24321963
TI  - Efficient, octave-spanning difference-frequency generation using few-cycle pulses
      in simple collinear geometry.
AB  - We present experimental observations and corresponding numerical simulations
      illustrating the difference-frequency generation of mid-infrared radiation using
      few-cycle near-infrared-to-visible pulses, which yields conversion efficiencies
      above 12% in beta-barium borate crystal. Type I and type II phase-matching are
      shown to yield qualitatively different intensity-scaling behavior, with the
      former showing higher overall efficiency, especially with the addition of a zero
      order wave plate for modifying the polarization state of the pulse, and the
      latter having a better stability of the spectrum versus input intensity. 

PMID- 24321964
TI  - Compact and low-loss silicon power splitter based on inverse tapers.
AB  - A compact, low-loss, optical power splitter based on inverse tapers is proposed
      and fabricated on a silicon-on-insulator platform. High efficiency mode evolution
      between the fundamental mode of the input waveguide and the super mode of the
      output waveguides is realized using optimized tapers. A 1*4 splitter with
      insertion loss lower than 0.4 dB and uniformity better than 0.68 dB in a
      wavelength range from 1510 to 1550 nm are demonstrated within a footprint of only
      ~75 MUm(2). These properties are very promising for ultrahigh density photonic
      integration applications.

PMID- 24321965
TI  - Low-temperature growth of near-infrared luminescent Bi-doped SiO(x)N(y) thin
      films.
AB  - Bi-doped siliconoxynitride (SiON:Bi) thin films were prepared by a sputtering
      method and the photoluminescence (PL) properties were studied. Without any
      thermal treatments, broad Bi-related luminescence was observed in the near
      infrared (NIR) range. The luminescence efficiency depended strongly on the film
      composition. It was found that N atoms play a crucial role for the formation of
      Bi NIR luminescence centers. The effect of annealing on the luminescence
      efficiency was also studied. The optimum annealing temperature to have the
      largest number of Bi NIR luminescence centers depended strongly on the film
      composition and it was lower for films with lower N concentration. The PL
      excitation spectra revealed that two different Bi NIR luminescence centers exist
      in the films. 

PMID- 24321966
TI  - Tuning of surface plasmon polaritons beat length in graphene directional
      couplers.
AB  - We investigate the tuning of the coupling of surface plasmon polaritons between
      two spatially separated graphene layers. We demonstrate that by slightly changing
      the chemical potential, a graphene coupler can switch from the bar to the cross
      state; as a consequence, the coupling coefficient in such structures can be
      easily controlled by means of an applied electrical signal. 

PMID- 24321967
TI  - Power-controlled phase-matching and instability of CW propagation in multicore
      optical fibers with a central core.
AB  - We present modulation instability analysis including azimuthal perturbations of
      steady-state continuous wave (CW) propagation in multicore-fiber configurations
      with a central core. In systems with a central core, a steady CW evolution regime
      requires power-controlled phase matching, which offers interesting spatial
      division applications. Our results have general applicability and are relevant to
      a range of physical and engineering systems, including high-power fiber lasers,
      optical transmission in multicore fiber, and systems of coupled nonlinear
      waveguides. 

PMID- 24321968
TI  - Optical clearing agents improve photoacoustic imaging in the optical diffusive
      regime.
AB  - Acoustic resolution photoacoustic microscopy (AR-PAM) takes advantage of weak
      acoustic scattering to image fine structures, such as the subcutaneous
      microvasculature, providing a spatial resolution on the order of tens of
      micrometers. However, the amplitude of AR-PAM deteriorates sharply with depth, as
      a result of light scattering and acoustic attenuation caused by structures such
      as the skin. Optical clearing techniques can enhance optical transmittance by
      decreasing the scattering of light through tissues. However, it is unknown
      whether optical clearing agents (OCAs) can be used to improve AR-PAM. We applied
      different types of OCAs to rat dorsal skin in an ex vivo study to determine the
      effects of OCAs on photoacoustic detection. We identified three OCAs that
      improved the photoacoustic amplitude for further in vivo testing. With the use of
      an appropriate penetration enhancer, PEG-400 significantly improved the
      photoacoustic amplitude for detection of deep-sealed blood vessels, while
      glycerol alone improved the image quality of shallow vessels. In contrast, DMSO
      application resulted in decreased photoacoustic amplitude in the in vivo trials. 

PMID- 24321969
TI  - Multiple reversals of optical binding force in plasmonic disk-ring nanostructures
      with dipole-multipole Fano resonances.
AB  - We study the optical far-field and near-field characteristics, and the optical
      force effects of plasmonic disk-ring nanostructures. There are multiple Fano
      features resulting from the scattering interferences of the hybridized modes from
      the disk's dipole and the ring's higher-order modes. In particular, it is found
      that the optical binding force between the disk and the ring shows multiple sign
      reversals spectrally, from the dipole-quadrupole regime up to the dipole-decapole
      regime. We show that the zero-force points can be categorized into two types: the
      positive-to-negative ones resulting from the Fano dip and the negative-to
      positive ones associated with the transitions between dipole-multipole modes. The
      multiple sign reversals of the optical forces are tunable by the geometrical size
      and gap of the disk and ring. Such characters make it possible to organize
      unusual optical matters from individual plasmonic nanoparticles. 

PMID- 24321970
TI  - Reducing disorder-induced losses for slow light photonic crystal waveguides
      through Bloch mode engineering.
AB  - We present theory and measurements of disorder-induced losses for low loss 1.5 mm
      long slow light photonic crystal waveguides. A recent class of dispersion
      engineered waveguides increases the bandwidth of slow light and shows lower
      propagation losses for the same group index. Our theory and experiments explain
      how Bloch mode engineering can substantially reduce scattering losses for the
      same slow light group velocity regime. 

PMID- 24321971
TI  - Use of radiation pressure for measurement of high-power laser emission.
AB  - We demonstrate a paradigm in absolute laser radiometry where a laser beam's power
      can be measured from its radiation pressure. Using an off-the-shelf high-accuracy
      mass scale, a 530 W Yb-doped fiber laser, and a 92 kW CO(2) laser, we present
      preliminary results of absolute optical power measurements with inaccuracies of
      better than 7% to 13%. We find negligible contribution from radiometric (thermal)
      forces. We also identify this scale's dynamic-force noise floor for a 0.1 Hz
      modulation frequency as 4 MUN/Hz(1/2) or, as optical power sensitivity, 600
      W/Hz(1/2).

PMID- 24321972
TI  - Dip-in depletion optical lithography of three-dimensional chiral polarizers.
AB  - We combine the concepts of dip-in and stimulated-emission-depletion-inspired
      optical lithography for the first time to fabricate three-dimensional (3D)
      nanostructures for photonics. For depletion of the photoinitiator ITX we employ a
      fiber-coupled laser diode at 639 nm wavelength. To demonstrate the performance of
      the experimental setup, we have fabricated 3D chiral layer-by-layer twisted
      woodpile structures with a lattice constant reduced by more than a factor of 2
      compared to earlier results. The fabricated chiral photonic crystals serve as
      dual-band polarizers for circular polarization at visible and telecom
      wavelengths. Spectroscopic measurements agree well with scattering-matrix
      calculations. 

PMID- 24321973
TI  - Photonic generation of pulsed microwave signals with tunable frequency and phase
      based on spectral-shaping and frequency-to-time mapping.
AB  - A scheme for photonic generation of pulsed microwave signals with tunable
      frequency and phase based on optical spectral-shaping and frequency-to-time
      mapping is proposed and experimentally demonstrated. The spectral shaping is
      realized by a tunable optical comb filter consisting of a differential group
      delay (DGD) element, a polarization modulator (PolM), and a polarizer. By passing
      a short optical pulse through the tunable comb filter and a dispersive element
      (DE), a pulsed microwave signal is generated after optical-to-electrical
      conversion. The phase of the generated microwave signal can be continuously tuned
      by tuning the voltage applied to the PolM. The frequency of the microwave signal
      can be tuned by changing the DGD and/or the dispersion of the DE. An experiment
      is performed. The generation of a pulsed microwave signal with tunable frequency
      and phase is demonstrated. 

PMID- 24321974
TI  - Cryogenically cooled, 149 W, Q-switched, Yb:LiYF4 laser.
AB  - We demonstrate a 149 W Yb:LiYF(4) laser with diffraction-limited beam quality at
      995 nm. The laser, Q-switched at 10 kHz pulse repetition frequency, produces
      linearly polarized 52 ns pulses with a slope efficiency of 73%. The combination
      of cryogenic cooling and a low (3.5%) quantum defect results in minimal thermo
      optic effects and high thermal efficiency. The measured heat load to the cryogen
      is 0.15 W per watt of output. These results show the potential for significant
      power scaling of Q-switched Yb:YLF lasers with excellent beam quality.

PMID- 24321975
TI  - Anisotropic electro-optic effect on InGaAs quantum dot chain modulators.
AB  - We investigated the anisotropic electro-optic (EO) effect on InGaAs quantum dot
      (QD) chain modulators. The linear EO coefficients were determined as 24.3 pm/V
      (33.8 pm/V) along the [011] direction and 30.6 pm/V (40.3 pm/V) along the [011-]
      direction at 1.55 MUm (1.32 MUm) operational wavelength. The corresponding half
      wave voltages (Vpis) were measured to be 5.35 V (4.35 V) and 4.65 V (3.86 V) at
      1.55 MUm (1.32 MUm) wavelength. This is the first report on the anisotropic EO
      effect on QD chain structures. These modulators have 3 dB bandwidths larger than
      10 GHz.

PMID- 24321976
TI  - Implementation of HIV-related clinical research in the international setting.

PMID- 24321977
TI  - Addressing standards of care in resource-limited settings.
AB  - : The choice between "best-known" standards of care (SOC) or "best available"
      standards as the control arm in a clinical trial is a fundamental dilemma in
      clinical research in resource-limited settings (RLS). When the health system is
      delivering less than an optimal level of care, using highest standard of care in
      a clinical trial may produce results that cannot be implemented or sustained
      locally. On the other hand, using interventions that are more feasible in the
      local setting may involve suboptimal care, and clinical outcomes may be affected.
      The need for improved standards in health systems in RLS, and the difficulty in
      securing them, has led many researchers advocate for policy changes at the
      national or international level to improve clinical care more systemically. SOC
      decisions in a clinical trial affect the level of benefit provided to study
      participants and the policy implications of the trial findings. SOC choices
      should provide high-quality care to help advance the health care system in host
      countries participating in the trial, but balancing the scientific and ethical
      objectives of SOC choices is difficult, and there is no single formula for
      selecting the appropriate SOC. Despite the challenges, well-designed and
      conducted clinical trials can and should make significant contributions to health
      systems in RLS. 

PMID- 24321978
TI  - Infection control best practices in clinical research in resource-limited
      settings.
AB  - Infection control activities in the international research setting include the
      development of meaningful and effective policies on specific topics such as hand
      and respiratory hygiene. Prevention of infection in health care workers and
      management of occupational exposure to transmissible agents are important aspects
      of the role of an infection control practitioner. Hand hygiene reduces health
      care associated infections and practices may be implemented in the research
      setting.

PMID- 24321979
TI  - Optimizing the protection of research participants and personnel in HIV-related
      research where TB is prevalent: practical solutions for improving infection
      control.
AB  - Tuberculosis (TB) is a leading cause of death among persons with HIV globally.
      HIV-related research in TB endemic areas raises some unique and important ethical
      issues in infection control related to protecting both research participants and
      personnel. To address such concerns, this article provides practical guidance to
      help research teams develop strategies to prevent TB transmission in studies
      involving persons with HIV in TB endemic settings.

PMID- 24321980
TI  - Ethical issues in adolescent HIV research in resource-limited countries.
AB  - Globally, there are 5 million young people aged 15-24 years living with HIV, and
      many more millions are at risk for HIV acquisition. Compelling research questions
      exist that require the involvement of young people and other vulnerable
      populations in HIV-related research in diverse settings around the world. Despite
      this, there remains a reluctance to involve adolescent participants, including
      young women, in clinical research. Complex and, at times, contradictory legal and
      ethical requirements can be a challenge. Ethical benchmarks can be applied to
      ensure that research meets high-level standards and is planned for appropriately.

PMID- 24321981
TI  - Regulatory challenges associated with conducting multicountry clinical trials in
      resource-limited settings.
AB  - International public health and infectious diseases research has expanded to
      become a global enterprise transcending national and continental borders in
      organized networks addressing high-impact diseases. In conducting multicountry
      clinical trials, sponsors and investigators have to ensure that they meet
      regulatory requirements in all countries in which the clinical trials will be
      conducted. Some of these requirements include review and approval by national
      drug regulatory authorities and recognized research ethics committees. A limiting
      factor to the efficient conduct of multicountry clinical trials is the regulatory
      environment in each collaborating country, with significant differences
      determined by various factors including the laws and the procedures used in each
      country. The long regulatory processes in resource-limited countries may hinder
      the efficient implementation of multisite clinical trials, delaying research
      important to the health of populations in these countries and costing millions of
      dollars a year.

PMID- 24321982
TI  - Setting the research agenda in a resource-limited setting--viewpoint.
AB  - The phenomenon of disproportionately large allocations of global health research
      resources to relatively limited components of the global health burden is widely
      acknowledged. Factors contributing to this are explored. The development of a
      national or regional research agenda is a critical step toward attempting to
      redress this imbalance. Key areas to be considered are a broad vision, dialogue,
      and commitment from those stakeholders comprising the "health research triangle":
      national policy makers and decision makers, key personnel in both health research
      and health care, and community representatives. The interdependent roles of
      human, material, and community resources are further examined.

PMID- 24321983
TI  - Managing multiple funding streams and agendas to achieve local and global health
      and research objectives: lessons from the field.
AB  - Multiple funding sources provide research and program implementation
      organizations a broader base of funding and facilitate synergy, but also entail
      challenges that include varying stakeholder expectations, unaligned grant cycles,
      and highly variable reporting requirements. Strong governance and strategic
      planning are essential to ensure alignment of goals and agendas. Systems to track
      budgets and outputs, as well as procurement and human resources are required. A
      major goal of funders is to transition leadership and operations to local
      ownership. This article details successful approaches used by the newly
      independent nongovernmental organization, the Centre for Infectious Disease
      Research in Zambia.

PMID- 24321984
TI  - Laboratory challenges conducting international clinical research in resource
      limited settings.
AB  - There are many challenges to performing clinical research in resource-limited
      settings. Here, we discuss several of the most common laboratory issues that must
      be addressed. These include issues relating to organization and personnel,
      laboratory facilities and equipment, standard operating procedures, external
      quality assurance, shipping, laboratory capacity, and data management. Although
      much progress has been made, innovative ways of addressing some of these issues
      are still very much needed.

PMID- 24321985
TI  - Ensuring participant safety and trial integrity with clinical trials oversight.
AB  - Clinical trial oversight is a critical element that ensures the protection of
      research participants and integrity of the data collected. The trial sponsor, a
      local Institutional Review Board, and independent monitoring committees all
      contribute with complementary but overlapping responsibilities. Consistency among
      these groups is essential for the smooth conduct of a clinical trial but may be
      challenging in resource-limited settings (RLS). Capacity building and training
      for RLS may improve clinical trials oversight and ultimately medical management.
      In this article, we review the components necessary for optimal clinical trial
      oversight and the issues that arise in the RLS, with some suggested strategies
      for improvement.

PMID- 24321986
TI  - Supporting research sites in resource-limited settings: challenges in
      implementing information technology infrastructure.
AB  - As information and communication technology infrastructure becomes more reliable,
      new methods of electronic data capture, data marts/data warehouses, and mobile
      computing provide platforms for rapid coordination of international research
      projects and multisite studies. However, despite the increasing availability of
      Internet connectivity and communication systems in remote regions of the world,
      there are still significant obstacles. Sites with poor infrastructure face
      serious challenges participating in modern clinical and basic research,
      particularly that relying on electronic data capture and Internet communication
      technologies. This report discusses our experiences in supporting research in
      resource-limited settings. We describe examples of the practical and
      ethical/regulatory challenges raised by the use of these newer technologies for
      data collection in multisite clinical studies.

PMID- 24321988
TI  - Palladium catalysed beta-selective oxidative Heck reaction of an electron-rich
      olefin.
AB  - A palladium catalysed oxidative beta-arylation of an electron-rich olefin is
      described. The reaction was under mild conditions; meanwhile, additives and
      directing groups are not needed. Various arylboronic acids worked well under the
      standard conditions. 

PMID- 24321987
TI  - The Haiti research-based model of international public health collaboration: the
      GHESKIO Centers.
AB  - For 3 decades, GHESKIO (the Groupe Haitien d'Etude du Sarcome de Kaposi et des
      Infections Opportunistes), the Haitian Ministry of Health, and Weill Cornell have
      pursued a tripartite mission of service, training, and translational research.
      The initial focus was on AIDS and tuberculosis. The mission has expanded to
      include the local community and now provides maternal-child health, family
      planning, cancer prevention and treatment, immunizations (including human
      papillomavirus, cholera), and primary education through vocational and
      microcredit programs. Outcome measures include a reduction in HIV prevalence from
      6.2% to the current 2.2%, extensive tuberculosis and cholera prevention and
      treatment programs, and national training programs for biomedical and community
      health workers.

PMID- 24321989
TI  - Exome sequencing and diffusion tensor imaging in developmental disabilities.
AB  - BACKGROUND: We had previously shown that arcuate fasciculus is poorly developed
      in patients with intellectual and developmental disabilities (IDD) using
      diffusion tensor imaging (DTI). In the present study, we used exome sequencing to
      identify the candidate variants in IDD patients with and without DTI
      abnormalities. METHODS: Eighteen children with IDD (age: 67 +/- 36 mo, 9 females)
      were included in the present study. The DTI was used to determine the integrity
      of arcuate fasciculus. The next-generation sequencing was performed on the Solid
      4 platform. A novel, analytical strategy was developed to identify a set of
      candidate genes of interest. We then searched for novel, nonsynonymous variants
      in the patients within this subset of genes and in known IDD genes. RESULTS:
      Seven novel, nonsynonymous (all of them were heterozygous, missense) variants
      belonged to ultraconserved genes that are known to cause abnormal brain
      morphology in mutant mice. Similarly, three novel, nonsynonymous (all of them
      were heterozygous, missense) variants belonged to known IDD genes. Two patients
      with underdeveloped arcuate fasciculus had novel, nonsynonymous variants in genes
      (MID1 and EN2) regulating axon guidance pathway. CONCLUSION: Exome sequencing
      identified several new genetic causes of IDD.

PMID- 24321991
TI  - Impact of afterload reduction strategies on regional tissue oxygenation after the
      Norwood procedure for hypoplastic left heart syndrome.
AB  - OBJECTIVES: Low cerebral tissue oxygenation saturations have been observed by
      near-infrared spectroscopy (NIRS) after the Norwood procedure. Altered cerebral
      vascular resistance and pharmacological afterload reduction redirecting blood
      flow away from the cerebral circulation are possible mechanisms. METHODS: Two
      different afterload reduction strategies were evaluated in patients with
      hypoplastic left heart syndrome or variants after the Norwood procedure. In
      patients of Group 1 (n=34), afterload reduction was controlled with sodium
      nitroprusside or with the alpha-blocker phentolamine. In addition, a
      phosphodiesterase-III inhibitor was administered. Patients of Group 2 (n=34)
      received a phosphodiesterase-III inhibitor only. Cerebral and somatic tissue
      oxygenation saturations and routine intensive care monitoring data were recorded
      for 24 h before and 48 h after the Norwood procedure. Mean values of the last 4
      preoperative (baseline) and of the first and last 4 postoperative hours (early
      and late course) were calculated. RESULTS: Baseline, early and late cerebral
      saturations were 58+/-7, 52+/-9 and 60+/-6% for Group 1 and 58+/-7, 52+/-12 and
      61+/-7% for Group 2 and somatic saturations were 59+/-8, 76+/-10 and 67+/-9% and
      58+/-9, 78+/-8 and 69+/-10%, respectively. Regional saturations were not
      different between groups. The postoperative cerebral tissue oxygen saturation was
      below 40% for 50 (0-1040) min in Group 1 and for 45 (0-720) min in Group 2
      (P=1.00). Preoperative cerebral NIRS values (OR 0.85 [0.76-0.96], P=0.007), age
      at operation (OR 1.39 [1.02-1.88], P=0.034) and early postoperative diastolic
      blood pressure (OR 0.88 [0.78-0.99], P=0.038) were associated with cerebral
      tissue oxygen saturations below 40% for more than 60 min. Patients with a
      prolonged period of low cerebral tissue oxygen saturation had longer duration of
      mechanical ventilation (69 (37-192) vs 60 (33-238) h, P=0.039) and afterload
      reduction therapy was terminated later (95 (47-696) vs 74 (39-650) h, P=0.006).
      Early mortality was 9.4% (3 of 32) compared with 2.8% (1 of 36) in the remainder
      (P=0.336). CONCLUSIONS: The postoperative decline of cerebral tissue oxygen
      saturation was observed with both afterload reduction strategies. The difference
      between cerebral and somatic NIRS values may indicate a mismatch between cerebral
      and splanchnic oxygenation. Other strategies to improve cerebral tissue
      oxygenation are warranted.

PMID- 24321990
TI  - Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse
      lung.
AB  - BACKGROUND: Caffeine is a nonspecific adenosine receptor antagonist used in
      premature neonates to treat apnea of prematurity. While its use may reduce the
      incidence of bronchopulmonary dysplasia (BPD), the precise mechanisms remain
      unknown. Evidence of increased adenosine levels are noted in chronic lung
      diseases including tracheal aspirates of infants with BPD. Utilizing a well
      characterized newborn mouse model of alveolar hypoplasia, we hypothesized that
      hyperoxia-induced alveolar inflammation and hypoplasia is associated with
      alterations in the adenosine signaling pathway. METHODS: Newborn murine pups were
      exposed to a 14-d period of hyperoxia and daily caffeine administration followed
      by a 14-d recovery period in room air. Lungs were collected at both time points
      for bronchoalveolar lavage (BAL) analysis as well as histopathology and mRNA and
      protein expression. RESULTS: Caffeine treatment increased inflammation and
      worsened alveolar hypoplasia in hyperoxia-exposed newborn mice. These changes
      were associated with decreased alveolar type II (ATII) cell numbers, increased
      cell apoptosis, and decreased expression of A2A receptors. Following
      discontinuation of caffeine and hyperoxia, lung histology returned to baseline
      levels comparable to hyperoxia exposure alone. CONCLUSION: Results of this study
      suggest a potentially adverse role of caffeine on alveolar development in a
      murine model of hyperoxia-induced alveolar hypoplasia.

PMID- 24321992
TI  - Intrapulmonary aspergilloma in an old tuberculous cavity with access to the
      bronchial system.

PMID- 24321993
TI  - Surgical revision after percutaneous mitral valve repair by edge-to-edge device:
      when the strategy fails in the highest risk surgical population.
AB  - OBJECTIVES: Percutaneous edge-to-edge devices for non-surgical repair of mitral
      valve regurgitation are under clinical evaluation in high-risk patients deemed
      not suitable for conventional surgery. To address guidelines for initial therapy
      decision, we here report on 13 cases of surgery after failed percutaneous edge-to
      edge mitral valve repair or attempted repair, and discuss methodology and
      prognostic factors for operative outcome in this high-risk situation. METHODS:
      Thirteen patients referred to our cardiothoracic unit after failed percutaneous
      mitral valve repair or attempted repair using the edge-to-edge technique, were
      treated surgically for mitral valve failure between June 2010 and December 2012.
      Pathology of mitral valve before and after interventional mitral valve repair
      (especially prevalent mode of failure) was evaluated and classified for each
      individual patient by echocardiography and intraoperative direct visualization.
      Number of implanted edge-to-edge devices were identified. Preoperative risk
      scores were matched with intraoperative observations and histopathological
      findings of valve tissue. Postoperative morbidity and mortality were analysed
      with respect to mitral valve and patient-related data. RESULTS: Three of 10
      patients were referred with severe mitral valve regurgitation/stenosis after
      initially successful percutaneous edge-to-edge therapy or attempted therapy. In 3
      patients, >= 2 edge-to-edge devices were implanted leading to very tight edge-to
      edge leaflet connection and fibrosis. All patients underwent successful surgical
      mitral valve replacement and concomitant complete cardiac surgery (CABG, aortic
      or tricuspid valve surgery, ASD closure and pulmonary vein isolation for atrial
      fibrillation). The likelihood of repair was reduced with respect to multiple edge
      to-edge technology. One device could not be harvested surgically because of
      embolization. One patient died on the second postoperative day due to sepsis with
      multiple organ failure. The remaining 12 patients were discharged with excellent
      valve prosthesis function and followed up to 2 years post-surgery. The current
      long-term survival rate is 77%. CONCLUSION: Our series demonstrate that highest
      risk patients can survive mitral valve surgery after failed multiple edge-to-edge
      interventional mitral valve repair. As long-term results of the MitraClip therapy
      are pending, we recommend close meshed follow-up of patients treated with the
      MitraClip device, especially within the first year of the index procedure as
      delays in salvage management, interventional or surgical, when the index
      procedure fails may increase morbidity and mortality.

PMID- 24321994
TI  - Early clinical outcomes of robot-assisted surgery for anterior mediastinal mass:
      its superiority over a conventional sternotomy approach evaluated by propensity
      score matching.
AB  - OBJECTIVES: We performed this study to assess early clinical outcomes of robot
      assisted surgery for anterior mediastinal mass by comparing results of the robot
      group with those of the sternotomy group after propensity score matching.
      METHODS: Between 2008 and 2012, 145 patients underwent resection of anterior
      mediastinal mass. Robot-assisted surgery was performed in 37 patients, and
      conventional surgery by sternotomy in 108 patients. Propensity score matching was
      done between two groups with variables of age, sex, size of the mass, myasthenia
      gravis, resection of other organ and pathological diagnosis. Thirty-four patients
      from the robot group and 34 from the open group were matched, fitting the model.
      The clinical outcomes of matched groups were compared. RESULTS: In the robot
      group, mediastinal cyst consisted of 47.1% (16 of 34), thymoma 32.4% (11 of 34),
      thymic carcinoma 8.8% (3 of 34), thymic hyperplasia 8.8% (3 of 34) and
      liposarcoma 2.9% (1 of 34). The mean duration of follow-up was 1.11 +/- 0.21 and
      1.85 +/- 0.19 years for the robot and open groups, respectively. There were no
      mortality or recurrence in both groups during the follow-up. There were no
      significant differences in operation time, postoperative white blood cell and C
      reactive protein increase, maximum visual analogue scale score for pain as well
      as postoperative intensive care unit care between the two groups. The robot group
      revealed a lesser number of drains (1.09 +/- 0.1 vs 1.41 +/- 0.1) and 24-h tube
      drainage (189.4 +/- 20.5 vs 397.6 +/- 52.6 ml), lower haemoglobin loss (0.54 +/-
      0.4 vs 1.35 +/- 0.1 g/dl) and haematocrit decrease (1.92 +/- 0.5 vs 3.85 +/-
      0.4%), shorter chest tube days (1.53 +/- 0.2 vs 3.06 +/- 0.2) and length of
      hospital stay (2.65 +/- 0.2 vs 5.53 +/- 0.8) after operation, which were all
      statistically significant. Although statistically insignificant, there were no
      postoperative complications in the robot group, but there were 5 (14.7%) in the
      open group (P = 0.063). CONCLUSIONS: In carefully selected patients with
      relatively smaller sized masses, robot-assisted surgery resulted in excellent
      early clinical outcomes with lesser tube drainage, lower blood loss, shorter tube
      days and length of hospital stay without any postoperative complications,
      compared with the matched open group. Further investigation for long-term
      clinical outcomes and oncological outcomes is required for a robotic approach.
      Particularly, long-term follow-up for the local recurrence rate according to the
      pathological diagnoses is required.

PMID- 24321995
TI  - Carbonic anhydrase IX is associated with early pulmonary spreading of primary
      colorectal carcinoma and tobacco smoking.
AB  - OBJECTIVES: Pulmonary metastasectomy is performed routinely in selected patients
      with metastatic spreading to the lungs. According to current guidelines, the
      tumour biology should be taken into account when selecting patients for a
      resection. Carbonic anhydrase IX (CA9) expression has been shown to be a common
      feature in primary tumour growth and metastasis and it negatively affects the
      clinical outcome in various malignancies. Data on CA9 in pulmonary metastases are
      lacking. METHODS: Forty-four patients with primary colorectal cancer (CRC) who
      underwent curative pulmonary metastasectomy were included in this study. We
      determined the expression of CA9 in pulmonary metastases and corresponding
      primaries by immunohistochemistry. The expression level was correlated with
      clinical parameters and patients' smoking habits. Furthermore, the impact of
      nicotine treatment on phosphorylation of STAT3, HIF-1alpha and CA9 expression was
      assessed in HT29 cells. RESULTS: High expression of CA9 in resected pulmonary
      metastases and corresponding primary tumours correlated with early spreading to
      the lung (both P < 0.001). Moreover, CA9 expression was affected by the smoking
      habits of the patients. Treating HT29 cells with nicotine resulted in an
      induction of CA9 in vitro. This induction was associated with STAT3
      phosphorylation and was independent of HIF-1alpha. CONCLUSIONS: This study
      provides first evidence of CA9 expression in pulmonary metastases of CRC and
      suggests a role of CA9 as a prognostic marker. Moreover, our in vitro and in vivo
      data indicate an association between tobacco smoking and CA9 expression.
      Immunohistochemical assessment of CA9 expression might serve as an additional
      tool in decision-making for selecting patients for pulmonary metastasectomy.

PMID- 24321996
TI  - Segmentectomy or lobectomy for early stage lung cancer: a meta-analysis.
AB  - Early stage lung cancer is routinely treated by lobectomy whenever clinically
      feasible, whereas the role of segmentectomy is controversial. The purpose of this
      study was to investigate the benefits of segmentectomy vs lobectomy for early
      stage lung cancer through a meta-analysis of published data. Eligible studies
      were identified from MEDLINE through February 2013. The manual selection of
      relevant studies was based on the summary analysis. We used published hazard
      ratios (HRs) if available or estimates from the published survival data.
      Lobectomy was chosen as the reference in all HR calculations. We compared the
      effect of segmentectomy and lobectomy for Stage I, Stage IA, Stage IA with
      tumours larger than 2 cm but smaller than 3 cm in size and Stage IA with tumours
      of 2 cm or smaller in 22 observational studies. The HRs of overall and cancer
      specific survival indicated significant benefits of lobectomy for Stage I, Stage
      IA and Stage IA with tumours larger than 2 cm but smaller than 3 cm at 1.20 (95%
      confidence interval [CI] 1.04-1.38; P = 0.011), 1.24 (95% CI 1.08-1.42; P =
      0.002) and 1.41 (95% CI 1.14-1.71; P = 0.001), respectively. For tumours 2 cm or
      smaller, segmentectomy provided an effect equivalent to that of lobectomy (HR
      1.05; 95% CI 0.89-1.24; P = 0.550). No significant publication bias was detected
      in any part of the analysis. These findings should be interpreted in the context
      of the inherent limitations of meta-analyses of retrospective studies, including
      the heterogeneity of patient characteristics.

PMID- 24321997
TI  - Effect of preoperative symptoms on outcomes after valve repair for degenerative
      aortic insufficiency.
AB  - OBJECTIVES: This study evaluated the effect of preoperative symptoms on long-term
      survival and valve reintervention in patients undergoing aortic valve repair
      (AVr) for severe degenerative aortic insufficiency (AI). METHODS: Between March
      1996 and June 2010, 274 patients underwent AVr for severe AI. Seventy-seven were
      performed in asymptomatic patients (Group I) and 197 were performed in
      symptomatic (Group II). Patients in Group I were younger (43.9 +/- 15.0 vs 54.1
      +/- 15.5 years; P < 0.001) with a higher proportion of bicuspid valves (n = 40,
      51.9% vs n = 68, 30.4%; P = 0.008). Group II had more patients with impaired left
      ventricular (LV; n = 36, 18.3% vs n = 5, 6.4%; P = 0.013). The mean follow-ups
      for Group I and Group II were 43.0 +/- 34.0 and 61.3 +/- 39.5 months,
      respectively. RESULTS: There was no in-hospital mortality. Overall, leaflet
      repair and reimplantation were higher in Group I (P = < 0.001 and P = 0.002,
      respectively), whereas subcommissural annuloplasty for tricuspid AV was higher in
      Group II (P = 0.002). Leaflet shaving and plication were performed in more
      patients in Group I (P = 0.002 for both). There was no difference in early
      complications, but during follow-up atrial fibrillation was more frequent in
      Group II (P = 0.03). There were 10 late cardiac deaths, all in Group II (P =
      0.04). Overall, 10-year cardiac survival was better in Group I (100 vs 77.3 +/-
      8.6%) but not significant (P = 0.1). At 10 years, freedom from >= AI2+ was 63.2
      +/- 8.1 vs 56.4 +/- 4.5% (P = 0.4), and freedom from AV reintervention was 81.8
      +/- 7.1 vs 89.0 +/- 2.8% (P = 0.36), in Groups I and II, respectively. In the
      whole cohort, 10-year freedom from AV reintervention was greater in patients with
      an end-diastolic diameter of <60 mm (90.0 +/- 7.6 vs 76.3 +/- 5.5%; P = 0.003).
      Multivariate analysis identified increasing age as the only independent predictor
      of overall survival (P = 0.03). The incidence of valve-related complications was
      similar. CONCLUSION: In asymptomatic patients with severe degenerative AI, AVr is
      associated with excellent long-term outcomes, while symptoms are associated with
      reduced long-term survival. In dilated LV, freedom from reoperation is lower. If
      feasible, early AVr is recommended in experienced centres.

PMID- 24321998
TI  - Time to refine N2 staging? cN2alpha and cN2beta based on local regional
      involvement provide a more accurate prognosis in surgically treated IIIA non
      small-cell lung cancer than N2 alone or the number of node stations involved.
AB  - OBJECTIVES: The number of stations of N2 nodes involved has been considered to be
      one of the most important prognostic factors for lung cancer. However, most
      reports have dealt with the pathological nodal status rather than with the
      clinical nodal status. We investigated the relationship between the prognosis and
      the location of the primary tumour and nodes involved. METHODS: A retrospective
      study was conducted in 1257 patients with primary lung cancer, which were
      resected between 1996 and 2009. Among them, 78 patients (6.2%) had cN2, c-stage
      IIIA, pN2 and non-small-cell lung cancer. We defined cN2alpha as only involvement
      of an upper mediastinal lymph node (UMLN) for a main tumour located in the upper
      lobe or as that of a lower mediastinal lymph node (LMLN) for a main tumour
      located in the lower lobe. cN2beta was defined as involvement of an LMLN for a
      main tumour located in the upper lobe with or without metastatic UMLN or as that
      of a UMLN for a main tumour located in the lower lobe with or without metastatic
      LMLN. We analysed preoperative clinical factors, as well as overall and disease
      free survival. RESULTS: The overall 5-year survival rate was 30.6%, and the
      disease-free 5-year survival rate was 22.6%. The disease-free 5-year survival
      rate for a tumour located in an upper lobe was significantly better than that for
      a tumour located in a lower lobe (27.9 vs 11.1%, P = 0.007). A significant
      difference in survival was seen between cN2alpha and cN2beta (29.6 vs 0%, P <
      0.001), but not between cN2 single and multiple (23.4 vs 19.5%, P = 0.123). A
      multivariate analysis with Cox's proportional hazards model revealed that
      cN2alpha independently predicted good disease-free survival. The sensitivity,
      specificity and positive predictive value for pN2 single based on clinical CT
      findings were 72.7, 48.2 and 35.6%, respectively. CONCLUSIONS: Clinical
      mediastinal lymph node status based on the location of the primary tumour and the
      node involved was an important preoperative prognostic factor. Thus, this factor
      should be considered when planning and evaluating clinical trials. Another
      important finding was that clinical single-station N2 is not always pathological
      single-station N2 disease.

PMID- 24321999
TI  - Bacterial nucleoid structure probed by active drag and resistive pulse sensing.
AB  - Recent biophysical approaches have provided key insights into the enthalpic and
      entropic forces that compact the nucleoid in the cell. Our biophysical approach
      combines two complementary, non-invasive and label-free techniques: a precisely
      timed steerable optical trap and a high throughput microcapillary Coulter
      counter. We demonstrate the ability of the latter technique to probe the physical
      properties and size of many purified nucleoids, at the individual nucleoid level.
      The DNA-binding protein H-NS is central to the organization of the bacterial
      genome. Our results show that nucleoids purified from the Deltahns strain in the
      stationary phase expand approximately five fold more than the form observed in WT
      bacteria. This compaction is consistent with the role played by H-NS in
      regulating the nucleoid structure and the significant organizational changes that
      occur as the cell adapts to the stationary phase. We also study the permeability
      to the flow of ions and find that in the experiment nucleoids behave as solid
      colloids. 

PMID- 24322000
TI  - We need to get another life after retirement.

PMID- 24322001
TI  - Exploring the electrostatic energy landscape for tetraloop-receptor docking.
AB  - It has long been appreciated that Mg(2+) is essential for the stabilization of
      RNA tertiary structure. However, the problem of quantitative prediction for the
      ion effect in tertiary structure folding remains. By using the virtual bond RNA
      folding model (Vfold) to generate RNA conformations and the newly improved
      tightly bound ion model (TBI) to treat ion-RNA interactions, we investigate
      Mg(2+)-facilitated tetraloop-receptor docking. For the specific construct of the
      tetraloop-receptor system, the theoretical analysis shows that the Mg(2+)-induced
      stabilizing force for the docked state is predominantly entropic and the major
      contribution comes from the entropy of the diffusive ions. Furthermore, our
      results show that Mg(2+) ions promote tetraloop-receptor docking mainly through
      the entropy of the diffusive ions. The theoretical prediction agrees with
      experimental analysis. The method developed in this paper, which combines the
      theory for the (Mg(2+)) ion effects in RNA folding and RNA conformational
      sampling, may provide a useful framework for studying the ion effect in the
      folding of more complex RNA structures. 

PMID- 24322002
TI  - Influence of FcgammaRIIIA genetic polymorphism on T-lymphocyte depletion induced
      by rabbit antithymocyte globulins in kidney transplant patients.
AB  - INTRODUCTION: Polyclonal antithymocyte globulins (ATG) have been used in
      transplantation for several decades, but the sources of the interindividual
      variability of their effect are poorly understood. An influence of the FCGR3A
      158V/F genetic polymorphism on the horse ATG concentration-effect relationship
      was reported in kidney transplant patients. The objective of the present study
      was to confirm the influence of the FCGR3A polymorphism on the extent of
      lymphocyte depletion in kidney transplant patients treated with rabbit
      antithymocyte globulin (r-ATG). MATERIALS AND METHODS: Of the 194 transplant
      patients treated with r-ATG between 1998 and 2002 in our institution, 69 patients
      were eligible and included in this retrospective study. Biomarkers of response
      were CD3 and CD4 counts. Dose-effect data were analyzed using a population
      approach, and a two-compartment turnover model with stimulation of lymphocyte
      'output'. Since r-ATG concentrations were not available, a K-PD model was used.
      The influence of FCGR3A genotype on estimated parameters was investigated.
      RESULTS: The r-ATG infusion rate leading to a 50% stimulation of CD3+ output
      (EDK(50)), which is inversely related to patient sensitivity to r-ATG treatment,
      decreased with the number of V alleles (P=0.0016). CONCLUSION: The genetic
      polymorphism of FCGR3A influences r-ATG effect on CD3 count in kidney transplant
      patients, those with the V allele being more sensitive to antilymphocyte serum.
      These results also suggest that r-ATG act, at least in part, by antibody
      dependent cellular cytotoxicity.

PMID- 24322003
TI  - Single-nucleotide polymorphisms of ABCG2 increase the efficacy of tyrosine kinase
      inhibitors in the K562 chronic myeloid leukemia cell line.
AB  - OBJECTIVE: The tyrosine kinase inhibitors (TKIs) used in the treatment of chronic
      myeloid leukemia are substrates for the efflux transport protein ATP-binding
      cassette subfamily G member 2 (ABCG2). Variations in ABCG2 activity might
      influence pharmacokinetics and therapeutic outcome of TKIs. The role of ABCG2
      single-nucleotide polymorphisms (SNPs) in TKI treatment is not clear and
      functional in-vitro studies are lacking. The aim of this study was to investigate
      the consequences of ABCG2 SNPs for transport and efficacy of TKIs [imatinib, N
      desmethyl imatinib (CGP74588), dasatinib, nilotinib, and bosutinib]. MATERIALS
      AND METHODS: ABCG2 SNPs 34G>A, 421C>A, 623T>C, 886G>C, 1574T>G, and 1582G>A were
      constructed from ABCG2 wild-type cDNA and transduced to K562 cells by retroviral
      gene transfer. Variant ABCG2 expression in cell membranes was evaluated and the
      effects of ABCG2 SNPs on transport and efficacy of TKIs were measured as the
      ability of ABCG2 variants to protect against TKI cytotoxicity. RESULTS: Wild-type
      ABCG2 had a protective effect against the cytotoxicity of all investigated
      compounds except bosutinib. It was found that ABCG2 expression provided better
      protection against CGP74588 than its parent compound, imatinib. ABCG2 421C>A,
      623T>C, 886G>C, and 1574T>G reduced cell membrane expression of ABCG2 and the
      protective effect of ABCG2 against imatinib, CGP74588, dasatinib, and nilotinib
      cytotoxicity. CONCLUSION: These findings show that the ABCG2 SNPs 421C>A, 623T>C,
      886G>C, and 1574T>G increase the efficacy of investigated TKIs, indicating a
      reduced transport function that might influence TKI pharmacokinetics in vivo.
      Furthermore, the active imatinib metabolite CGP74588 is influenced by ABCG2
      expression to a greater extent than the parent compound.

PMID- 24322004
TI  - How effective and cost-effective was the national mass media smoking cessation
      campaign 'Stoptober'?
AB  - BACKGROUND: A national smoking cessation campaign based on behaviour change
      theory and operating through both traditional and new media was launched across
      England during late 2012 ('Stoptober'). In addition to attempting to start a
      movement in which smokers would quit at the same time in response to a positive
      mass quitting trigger, the campaign set smokers the goal of being smoke-free for
      October and embodied other psychological principles in a range of tools and
      communications. METHODS: Data on quit attempts were obtained from 31,566 past
      year smokers during nationally representative household surveys conducted monthly
      between 2007 and 2012. The effectiveness of the campaign was assessed by the
      increase in national quit attempt rate in October relative to other months in
      2012 vs. 2007-2011. RESULTS: Relative to other months in the year, more people
      tried to quit in October in 2012 compared with 2007-2011 (OR=1.79, 95%CI=1.20
      2.68). In 2012 there was an approximately 50% increase in quitting during October
      compared with other months of the same year (9.6% vs. 6.6%; OR=1.50, 95%CI=1.05
      2.15), whereas in 2007-2011 the rate in October was non-significantly less than
      in other months of the same period (6.4% vs. 7.5%; OR=0.84, 95%CI=0.70-1.00).
      Stoptober is estimated to have generated an additional 350,000 quit attempts and
      saved 10,400 discounted life years (DLY) at less than L415 per DLY in the modal
      age group. CONCLUSIONS: Designing a national public health campaign with a clear
      behavioural target (making a serious quit attempt) using key psychological
      principles can yield substantial behaviour change and public health impact.

PMID- 24322005
TI  - Adolescent illicit drug use and subsequent academic and psychosocial adjustment:
      an examination of socially-mediated pathways.
AB  - BACKGROUND: Questions remain regarding the consequences of illicit drug use on
      adolescent adjustment and the nature of mechanisms that may explain these
      consequences. In this study, we examined whether early-onset illicit drug use
      predicts subsequent academic and psychosocial adjustment and whether associations
      are socially-mediated by decreased school engagement and increased peer deviancy.
      METHOD: 4885 adolescents were followed throughout secondary school. We used
      regressions to determine whether illicit drug use in grade 7 predicted academic
      achievement, school dropout, depressive symptoms, and conduct problems in grades
      10-11, adjusting for potential confounders. We used path analysis to test whether
      significant associations were mediated by school engagement and peer deviancy in
      grade 8. RESULTS: Illicit drug use predicted conduct problems and school dropout,
      but not academic achievement and depressive symptoms. The association between
      illicit drug use and conduct problems was fully mediated by increased peer
      deviancy. The association between illicit drug use and school dropout was
      partially mediated by increased peer deviancy, but remained mostly direct. No
      indirect association via decreased school engagement was found. Examination of
      reverse pathways revealed that conduct problems and academic achievement in grade
      7 predicted drug use in grades 10-11. These associations were mediated by peer
      deviancy and school engagement (conduct problems only). CONCLUSION: Adolescent
      illicit drug use influences the risk of school dropout and conduct problems in
      part by contributing to deviant peer affiliation. Reciprocal social mediation
      characterizes the association between drug use and conduct problems. A reverse
      mechanism best explains the association with academic achievement.

PMID- 24322006
TI  - The fate of anticancer drug, ellipticine in DPPC and DMPC liposomes upon
      interaction with HSA: a photophysical approach.
AB  - Interaction of anticancer drug, ellipticine with Human Serum Albumin (HSA) and
      release of this encapsulated drug from two individual liposomes namely 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) upon addition of HSA have been studied by steady state and
      time resolved fluorescence spectroscopy. It was observed that HSA penetrates into
      the liposomes through hydrophobic interaction which reduces the packing order of
      the lipid bi-layer and leads to a quenching in fluorescence intensity of
      ellipticine. DPPC is more dehydrated hence more hydrophobic due to its higher
      phase transition temperature (42 degrees C) as compared to that of DMPC (23
      degrees C). Therefore, HSA exhibits more affinity towards DPPC than it does
      towards DMPC. The time resolved components revealed that penetration of HSA into
      liposomes results in migration of the drug molecules from liposomes to
      hydrophobic pocket of HSA. Incorporation of HSA in both the liposomes increases
      the rotational relaxation time of ellipticine. The fact confirms that HSA
      penetrates into the liposome and forms bigger complex. 

PMID- 24322007
TI  - The association between acetaminophen and asthma: is there anything to learn from
      the upper airways?
AB  - PURPOSE OF REVIEW: To examine the literature evidence for the association between
      acetaminophen (paracetamol) use and development of rhinitis. RECENT FINDINGS:
      Increased use of acetaminophen (paracetamol) as the favored antipyretic during
      pregnancy and infancy has been hypothesized to be a risk factor for the
      development of asthma. There is a paucity of well designed birth cohort studies
      to examine paracetamol as a risk factor in the development of rhinitis.
      Confounding by antibiotic use, viral infections, and recall bias are problematic
      for many of the studies that are published. SUMMARY: Prospective birth cohorts
      need to dedicate sufficient time and research personnel to adequately assess
      paracetamol exposure as a primary variable of interest rather than as an
      incidental exposure variable collected during routine questionnaire
      administration.

PMID- 24322009
TI  - Histone deacetylases and their inhibitors: new implications for asthma and
      chronic respiratory conditions.
AB  - PURPOSE OF REVIEW: The importance of the role of histone deacetylase enzymes in
      the pathogenesis of asthma and chronic respiratory diseases is increasingly being
      recognized. Similarly, the potential clinical utility of histone deacetylase
      enzymes in the treatment of disease is emerging. In this review, the role of
      histone deacetylases (HDAC) and their inhibitors in asthma and chronic
      obstructive pulmonary disease is discussed. RECENT FINDINGS: HDAC are able to
      catalyze the hydrolysis of acetyl groups on lysine residues of histones, causing
      the condensation and coiling of chromosomal DNA around histones, and therefore
      regulating gene expression. Histone deacetylase inhibitors act specifically or
      broadly on HDAC and also on nonhistone targets. Some have been used in the
      oncology therapeutic field for some years, but it is only more recently that they
      have been suggested in the treatment of asthma and other inflammatory lung
      diseases. SUMMARY: Important developments have been made in the understanding of
      histone deacetylase expression in normal and diseased airways and pulmonary
      tissue as well as effects of histone deacetylase inhibitors on structural and
      inflammatory cells in the lung, including cell proliferation, differentiation and
      apoptosis and senescence. Many of these discoveries may have implications in
      addressing airway inflammation, airway remodeling and airway hyperresponsiveness
      in asthma.

PMID- 24322010
TI  - The online social self: an open vocabulary approach to personality.
AB  - OBJECTIVE: We present a new open language analysis approach that identifies and
      visually summarizes the dominant naturally occurring words and phrases that most
      distinguished each Big Five personality trait. METHOD: Using millions of posts
      from 69,792 Facebook users, we examined the correlation of personality traits
      with online word usage. Our analysis method consists of feature extraction,
      correlational analysis, and visualization. RESULTS: The distinguishing words and
      phrases were face valid and provide insight into processes that underlie the Big
      Five traits. CONCLUSION: Open-ended data driven exploration of large datasets
      combined with established psychological theory and measures offers new tools to
      further understand the human psyche.

PMID- 24322011
TI  - Monitoring cognitive functioning: psychometric properties of the brief test of
      adult cognition by telephone.
AB  - Assessment of cognitive functioning is an important component of telephone
      surveys of health. Previous cognitive telephone batteries have been limited in
      scope with a primary focus on dementia screening. The Brief Test of Adult
      Cognition by Telephone (BTACT) assesses multiple dimensions central for effective
      functioning across adulthood: episodic memory, working memory, reasoning, verbal
      fluency, and executive function. The BTACT is the first instrument that includes
      measures of processing speed, reaction time, and task-switching/inhibitory
      control for use over the telephone. We administered the battery to a national
      sample (N = 4,268), age 32 to 84 years, from the study of Midlife in the United
      States (MIDUS) and examined age, education, and sex differences; reliability; and
      factor structure. We found good evidence for construct validity with a subsample
      tested in person. Implications of the findings are considered for efficient
      neuropsychological assessment and monitoring changes in cognitive aging, for
      clinical and research applications by telephone or in person.

PMID- 24322013
TI  - Enabling brain plasticity and neurological recovery in the ischemic brain: effect
      of age and vascular risk factors as confounders.
AB  - Cerebral plasticity and neurological recovery can be stimulated in the ischemic
      brain by exogenous pharmacological and cell-based treatments. Neurons,
      neuroblasts and endothelial cells synergistically interact with each other as a
      regenerative triad, creating an environment in which neurological recovery takes
      place. Developmental genetic programs are reactivated. Brain neurons and
      capillary cells are enabled to sprout, and glial cells support plasticity
      processes. Until now, the large majority of studies were performed in young,
      otherwise healthy animals, which lack the risk factors and co-morbidities
      associated with human stroke. Recent behavioral, histochemical and molecular
      biological studies have shown that restorative brain responses may differ between
      young and old animals, and that they are also modulated by vascular risk factors,
      such as hyperlipidemia and diabetes, which are highly prevalent in ischemic
      stroke. We claim that age aspects, vascular risk factors and co-morbidities
      should more intensively be examined in future experimental studies. Confounding
      effects of age, risk factors and co-morbidities should carefully be considered in
      clinical proof-of-concept trials. 

PMID- 24322012
TI  - Introducing the short Dark Triad (SD3): a brief measure of dark personality
      traits.
AB  - Three socially aversive traits-Machiavellianism, narcissism, and psychopathy-have
      been studied as an overlapping constellation known as the Dark Triad. Here, we
      develop and validate the Short Dark Triad (SD3), a brief proxy measure. Four
      studies (total N = 1,063) examined the structure, reliability, and validity of
      the subscales in both community and student samples. In Studies 1 and 2,
      structural analyses yielded three factors with the final 27 items loading
      appropriately on their respective factors. Study 3 confirmed that the resulting
      SD3 subscales map well onto the longer standard measures. Study 4 validated the
      SD3 subscales against informant ratings. Together, these studies indicate that
      the SD3 provides efficient, reliable, and valid measures of the Dark Triad of
      personalities. 

PMID- 24322014
TI  - Cutaneous metastases from breast carcinoma: calretinin expression and estrogen,
      progesterone and Her2/neu status of the metastases, compared to primary cutaneous
      apocrine tumors.
AB  - Recently, it has been demonstrated how apocrine glands, as well as several
      cutaneous apocrine tumors, do not express calretinin. In the current report, we
      studied calretinin immunoexpression in 33 cases of cutaneous metastases of ductal
      breast carcinoma, as well as in seven primary cutaneous apocrine tumors. We also
      tested the hormonal status of all cases for estrogen receptors (ER), progesterone
      receptors (PR), and ERRB2. From the 33 metastases, 26 (78.79%) cases were
      calretinin-negative and seven cases expressed the marker. Five (15.15%) cases
      were triple-negative (ER-, PR-, Herceptest-). Of these five cases, three cases
      were calretinin+ and two cases were calretinin-. Three out of the seven cases
      that expressed calretinin were triple-negative. From the seven primary cutaneous
      apocrine tumors, only one showed focal expression of calretinin, and six of them
      showed a triple-negative immunophenotype. Only the ER+, PR+ case showed
      morphologic features on an "in situ" apocrine carcinoma. We concluded that our
      findings support the value of calretinin in the differential diagnosis between a
      metastasis from breast carcinoma into the skin and a primary cutaneous apocrine
      carcinoma (CAC), especially in triple-negative cases. However, hormonal markers
      plus calretinin would not be sufficient to discriminate between both diagnostic
      possibilities, and they are probably better used when integrated in a wide
      immunohistochemical panel. 

PMID- 24322015
TI  - Assessment of CD105, alpha-SMA and VEGF expression in gastric carcinomas.
AB  - In this study, we analyzed the microvessel density (MVD) for CD105+ and alpha
      SMA+ vessels and the VEGF immunoexpression in 38 gastric carcinomas. CD105+ MVD
      had superior values at the advancing edge compared with the intratumoral area, no
      matter of the analyzed clinico-pathological parameters, the difference being
      significant only in intestinal type, moderate differentiated carcinomas as well
      as in T2-T3 carcinomas, without lymph node metastases (p<0.05). Intratumoral
      expression of CD105+ MVD indicated significant differences related to
      histological type (p=0.006), depth of invasion (p=0.027) and lymph node
      metastases (p=0.009), but without statistical association in case of the
      advancing edge or metastases. The assesses of alpha-SMA+ MVD indicated no
      differences between intratumoral and advancing edge areas, no matter of the
      analyzed parameters, excepting intestinal type carcinomas, which presented
      significant high values (p=0.003) at the advancing edge. VEGF score revealed
      significant differences related to histological type (p=0.020), differentiation
      degree of the intestinal type carcinomas (p=0.036) and depth of invasion
      (p=0.049). In case of metastases, the levels of VEGF expression were higher in
      the primary tumor, without statistically significant differences (p>0.05). It
      were significant differences of intratumoral VEGF expression depending on CD105+
      MVD values (p=0.019), but not with alpha-SMA+ MVD (p>0.05). Angiogenesis
      evaluated through the VEGF and MVD (CD105+ and alpha-SMA+) expression is
      correlated with the progression and metastasis of gastric cancer and could be
      considered a prognostic marker of these tumors. 

PMID- 24322016
TI  - Assessment of the relationship between Helicobacter pylori infection, endoscopic
      appearance and histological changes of the gastric mucosa in children with
      gastritis (a single center experience).
AB  - BACKGROUND: Helicobacter pylori infection is an important cause of gastritis in
      childhood, its role in the pathogenesis of peptic ulcer disease in adults and
      children being generally known. In some cases, there are therapeutic management
      issues, because they do not heal or they often relapse, although treatment
      regimens are applied as recommended. Our aim was to analyze the relationship
      between endoscopic appearance and histological changes of the gastric mucosa in
      children with gastritis associated with H. pylori infection, in which persistent
      infection after treatment was found. MATERIALS AND METHODS: It was a prospective
      study on 1332 children assessed in our Service (Ist Pediatric Clinic, Tirgu
      Mures, Romania), between January 2008 and January 2013, for gastritis with
      various etiologies. There were 609 cases of gastritis-associated with H. pylori
      infection. RESULTS: The average age of patients was 13.21 years; the higher
      incidence was noted in 13-18-year-old group, female gender and rural areas
      provenience; a number of 544 patients diagnosed with gastritis with H. pylori
      were reassessed subsequently; after treatment, gastritis has healed and the
      infection was eradicated in 88.23% cases after a month, while in 64 patients
      infection persisted. After a second regimen, endoscopic-histological
      modifications persisted in 31 (5.69%) cases; 1.28% cases remained positive for
      longer. CONCLUSIONS: H. pylori infection was associated with high age group, as
      well as with endoscopic modifications; also, the presence of H. pylori was
      correlated with histopathologic diagnostic. We try to emphasize the importance of
      assessing bacterial resistance to antibiotics, studying of bacterial genome and
      genetic susceptibility of human subjects.

PMID- 24322017
TI  - The poor prognosis factors in G2 neuroendocrine tumor.
AB  - BACKGROUND: The G2 neuroendocrine tumors (NET) or well-differentiated
      neuroendocrine carcinomas (2010 WHO Classification of Tumours of the Digestive
      System) embrace different types of evolution despite the fact that they actually
      are included in the same group of prognosis based on mitotic count and the Ki-67
      proliferation index. AIM: We studied the pathological and clinical aspects in
      patients with G2 NET. MATERIALS AND METHODS: This is a retrospective pilot
      observational study in patients admitted between January 2008 and January 2013 in
      "Constantin I. Parhon" National Institute of Endocrinology, Bucharest, Romania.
      They were evaluated based on the pathological report, imagistic scan, and
      neuroendocrine markers. RESULTS: Nine patients (female/male ratio: 5/4) with G2
      NET were included (mean age at diagnosis 54.11 years). Surgery was performed in
      66.66% of cases. 44.44% of tumors had unknown origin. 22.22% of patients had
      negative immunostain for chromogranin A. Synaptophysin was positive in all cases.
      Neuronal specific enolase (NSE) was performed in 44.44% of cases and it was
      positive in all these situations. 88.88% of patients had high neuroendocrine
      markers. Multiple tumors were found in two cases (follicular thyroid adenoma, and
      a carcinoma of the port vein, respective bilaterally pheochromocytomas). The
      youngest patient (39-year-old) had atypical onset with bilateral adrenal tumors
      (positive for CHROMO, EMA, CK-19, CK-20, negative for SOMATO, CK-7, S-100,
      glucagon, CD57, and a Ki-67 of 15%). Death was registered in two cases, both with
      bone metastases. DISCUSSION: Some poor prognosis factors may be taken into
      account as lack of CHROMO immunostain, young age at diagnosis, genetic
      background, and lack of therapy options as surgery. Larger databases will provide
      more information. CONCLUSIONS: It is possible that the G2 NET group of tumors
      actually includes some different subtypes or in fact, a late diagnosis of the
      tumor might be associated with a poor diagnosis.

PMID- 24322018
TI  - c-Kit expression in somatosensory nuclei of lower medulla oblongata.
AB  - Protein kinase signal-transduction pathways play critical roles in regulating
      nociception. The c-kit receptor contributes to pain regulation in the spinal cord
      and is present on both peripheral and central terminals. Expression of c-kit was
      demonstrated in human trigeminal and spinal ganglia. However, the brainstem
      expression of c-kit was overlooked. We aimed to evaluate it by
      immunohistochemistry, on eight samples of human lower medulla oblongata. We used
      two clones of CD117/c-kit antibodies, from different manufacturers, and
      neurofilament antibodies. Positive expression of CD117/c-kit was found within the
      spinal trigeminal nucleus, the gracilis, cuneate, and lateral cuneate nuclei, and
      within the olivary complex. CD117/c-kit positive interstitial networks of these
      nuclei were positively labeled with neurofilaments. CD117/c-kit labeled the
      olivary neurons, but not the magnocellular neurons of the trigeminal, gracilis
      and cuneate nuclei. c-kit interstitial systems of brainstem could play so an
      important role for the functional status along the somatosensory neural circuits.

PMID- 24322019
TI  - Immunofluorescence expression of Ki-67, p53 and cyclin inhibitors (p16ink4a, p21
      and p27) in low-grade cervical lesions versus high-grade cervical lesions.
      Research study on cell cultures.
AB  - OBJECTIVE: The aim of this research was to assess the immunofluorescence
      expression (IFE) of cell cycle regulators p16ink4a, p21, p27, in association with
      proliferation and prognosis factors Ki-67, p53 respectively, in cell cultures,
      obtained from different types of cervical intra-epithelial lesions. The final
      purpose was to distinguish a best marker able to identify with high accuracy the
      high-grade squamous intra-epithelial lesion. MATERIALS AND METHODS: The study was
      carried out on 68 epithelial cell cultures. Three senior specialists have
      analyzed 500 cells/case individually. The statistic analysis for correlation
      between used markers has been performed. RESULTS: The study batch revealed a very
      low expression of investigated parameters (<1%) in negative cases for malignancy
      and intraepithelial lesion (NMIL), a progressive exponential expression in low
      grade squamous intraepithelial lesion (LSIL), and a very high expression in high
      grade squamous intra-epithelial lesion (HSIL) and invasive squamous cervical
      carcinoma (ISCC). Ki-67 and p53 were overexpressed in nuclei both in LSIL and
      HSIL. A slightly direct correlation between p21 and Ki-67 (r=0.35, p<0.001) was
      observed in HSIL. Statistically significant correlations were noticed between
      some markers: p16ink4a and p27 (r=0.4, p=0.03), p16ink4a and Ki-67 (r=-0.4,
      p=0.002). CONCLUSIONS: The most reliable parameters for assessing HSIL and ISCC
      proved to be Ki-67 and p16ink4a. Both were with percentages and intensity of IFE
      around 100% and higher immunoexpression within the nucleus of cell cultures. Our
      study reveals that p27 cyclin inhibitor was not reliable in differentiating
      between LSIL and HSIL.

PMID- 24322020
TI  - Morphological and functional aspects of sciatic nerve regeneration after crush
      injury.
AB  - Experimental models for the investigation of nerve regeneration are critical in
      studying new strategies able to promote the repair process. The aim of the
      present work was to characterize morphological and functional aspects of sciatic
      nerve regeneration after mechanical crush injury in rodents. Morphological
      changes were assessed after a four minutes sciatic nerve injury induced by means
      of a standardized compression clip. Rat nerve samples were collected before
      injury and after 24 hours, four days, two weeks, and four weeks after injury,
      respectively. In an additional group with unilateral sciatic nerve injury,
      animals were evaluated for four weeks using walking track analysis and the
      sciatic static index (SSI) measured in both rearing and normal standing position.
      Histological study showed important axonal degeneration at four days and axonal
      regeneration at four weeks after injury. We observed no significant differences
      between SSI in rearing and normal standing stance and a strong correlation
      between SSI values measured in the two positions during the evaluation period.
      Positive correlations were also found for the footprint parameters. Our data
      provide a baseline characterization of the sciatic nerve crush injury that will
      further allow the investigation of peripheral nerve regeneration in the presence
      of potential neuroprotective agents in post-traumatic nerve repair. 

PMID- 24322021
TI  - Apoptotic markers in photoinduced cutaneous carcinoma.
AB  - Cutaneous carcinomas are malignant lesions, which most commonly occur on photo
      aggressed site. The purpose of our study was to evaluate the immunohistochemical
      expression of three apoptotic markers (p53, Bax, and Bcl-2) in photoinduced basal
      and squamous cell carcinoma. The study was performed on 24 patients diagnosed
      with these forms of cutaneous carcinoma localized on photoexposed regions: 14
      cases of basal cell carcinoma (BCC) and 10 cases of squamous cell carcinoma
      (SCC), classified accordingly WHO 2003. The immunohistochemical study performed
      on the three proteins involved in the apoptotic process revealed certain specific
      features in their manner of expression, which do not correlate or respect the
      critical determinant rule (Bcl-2/Bax>1). Basal cell carcinoma expresses higher
      levels of Bcl-2, with a better prognosis, a less aggressive evolution, and no
      metastasis. Squamous cell carcinoma, on the other hand, expresses lower levels of
      Bcl-2, but the clinical outcome is more aggressive, the tumor has a faster
      evolution and may metastasize. P53 protein respects the profile given in
      literature data, having a higher score in squamous cell carcinoma versus basal
      cell carcinoma. According to the tumor localization on photo-aggressed sites, we
      have considered that ultraviolet rays play an important role in initiation of
      carcinogenesis through still occult mechanisms that may induce these particular
      or rather "bizarre" expressions of apoptotic markers.

PMID- 24322022
TI  - Clinico-pathological and molecular subtypes of male breast carcinoma according to
      immunohistochemistry.
AB  - INTRODUCTION: Male breast carcinoma is a rare condition, but with a trend of
      increase frequency. In our study, we investigate the clinico-pathological
      features and overall survival at 35 male cases of primary invasive breast
      carcinoma correlated with molecular subtypes defined by immunohistochemical
      profile. METHODS: Based on immunohistochemical expression profiles of estrogen
      receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2)
      and Ki67, EGFR and CK5/6, the male breast cancers were classified into the
      following molecular subtypes: Luminal A, Luminal B, HER2+, triple negative and
      unclassified. RESULTS: In our study, we identified 65.7% as Luminal A subtype and
      28.6% as Luminal B subtype. The difference was represented by two (5.7%) cases of
      triple negative subtype, but due to low number of patients, no correlations or
      prognostic significance could be assessed in these cases. No HER2 or unclassified
      subtypes were identified. CONCLUSIONS: Luminal A tumors are the most frequent
      subtype in MBC, with a better outcome than Luminal B subtype. We recorded high
      levels of ER and PR expression, which predict a better response to adjuvant
      hormonal therapy. At the time of diagnosis, most of the patients were aged and
      with an advance clinical stage, this requiring implementation of screening
      programs and increase education of population in order to an early detection.

PMID- 24322023
TI  - Anatomical evidence regarding the existence of sustentaculum facies.
AB  - The face, seen as a unitary region is subject to the gravitational force. Since
      it is the main relational and socialization region of each individual, it
      presents unique ways of suspension. The elevation system of the face is complex,
      and it includes four different elements: the continuity with the epicranial
      fascia, the adhesion of superficial structures to the peri- and inter-orbital
      mimic muscles, ligaments adhesions and fixing ligaments of the superficial layers
      to the zygomatic process, and also to the facial fat pad. Each of these four
      elements were evaluated on 12 cephalic extremities, dissected in detail, layer by
      layer, and the images were captured with an informatics system connected to an
      operating microscope. The purchased mesoscopic images revealed the presence of a
      superficial musculo-aponeurotic system (SMAS) through which the anti-gravity
      suspension of the superficial facial structures become possible. This system acts
      against face aging and all four elevation structures form what the so-called
      sustentaculum facies. The participation of each of the four anatomic components
      and their approach in the facial rejuvenation surgeries are here in discussion. 

PMID- 24322024
TI  - Pilot preliminary study on the morpho-functional integration level of the auricle
      elastic cartilage transplanted in different tissue structures.
AB  - BACKGROUND: The nose is a complex and defining organ not only for its
      respiratory, olfactory and phonatory function but also for facial esthetics. It
      is plastic and reconstructive techniques are at the same time an
      otorhinolaryngological issue and an interdisciplinary one. MATERIALS AND METHODS:
      Among the materials used for reconstructive-reparatory surgery of the nose, we
      can distinguish the elastic ear cartilage transplant from patients own auricle.
      By analogy, we used in our experiment the rabbit ear as donor site and three
      radically different types of tissue as integrating structures. The modifications
      of the cartilages transplanted into abdominal subcutaneous tissue, muscles of the
      hip and under the skull periosteum were monitored through monthly sacrificing of
      the experimental animals. RESULTS: No matter of the presence or lack of own
      perichondrium coverage the cartilage pieces showed radical transformation to
      total changes in structure from perichondral fibrosis to endochondral
      ossification and even complete resorption. CONCLUSIONS: We consider that at least
      a part of the reconstructive and esthetic plastic surgery failure comes from not
      knowing these significant changes that take place on the insertion site of own
      transplanted cartilage. The future surgical guidelines should remember the
      phenomena described for the first time in our research.

PMID- 24322025
TI  - Patient, tumor and therapeutic features related to recurrence of ductal carcinoma
      in situ (DCIS).
AB  - To evaluate the correlations between patient, tumor and therapeutic features and
      DCIS recurrence after primary treatment, a cohort of 132 cases of DCISs, treated
      at "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania, between
      1999 and 2010, were studied. Present study showed that age <45 years at diagnosis
      and presence of the necrosis were significantly correlated with recurrence,
      meanwhile nuclear grade is significantly correlated with quicker relapse meaning
      that for high-grade lesions recurrence occurs usually during the first 36 months
      of follow-up, meanwhile for non-high-grade lesions recurrence usually occurs
      after 36 months of follow-up. Also, the study showed that a important factor
      correlated with recurrence (both local and overall) for patients treated with
      breast conservative surgery (BCS) was the status of the resection margins as well
      as the association of adjuvant radiotherapy. Overall recurrence rate was 9.(84)%
      and during a mean follow-up of 62.99 months with limits between 24 (imposed by
      study) and 153 months, standard deviation 29.28. 

PMID- 24322026
TI  - Endodontic configuration of the lower incisors in a Romanian population: a
      radiological study.
AB  - The significant rate of failure of endodontic treatment to lower incisors was
      attributed to poor knowledge of their endodontic morphology. As emphasized by
      Tinelli ME et al. (2011), the morphology of the endodontic system is strongly
      related to ethnicity, making possible the existence of important anatomical
      variations at different population groups. The present study analyzes, using
      radiological means, the endodontic anatomy of lower incisors extracted from a
      Romanian population. Five hundred seventy-five lower central and lateral incisors
      were radiographed and Weine's classification was used to evaluate their
      endodontic morphology. After processing the data, it was concluded that 81% of
      the studied teeth have one canal and the remaining 19% have two canals. In terms
      of endodontic configuration, 81% of 575 studied teeth are Weine Type I, 17% Type
      II, 1% Type III and 1% Type IV. Results obtained in this study are within
      existing international endodontic literature. Type II and IV configurations have
      a high degree of treatment difficulty. This requires thorough clinical and
      radiological examination of several incidents, possibly cone beam computed
      tomography (CBCT) and individualized therapeutic means to ensure treatment
      success. This study is the first of this magnitude in the Romanian specialty
      literature. 

PMID- 24322027
TI  - Anatomical and clinical considerations regarding the greater palatine foramen.
AB  - OBJECTIVE: In this study, we mapped the topography of the greater palatine
      foramen (GPF), within the South-Eastern European population, according to
      clinically identifiable anatomical landmarks. MATERIALS AND METHODS: We used 100
      dry adult human skulls, of which 75 were bilaterally dentate, whereas 25 were
      partially edentulous. RESULTS: The shape of the GPF was oval in 84% of the cases.
      The foramen was located internally from the third molar in 73% of the skulls. The
      greater palatine canal showed an antero-infero-medial direction in 82% of the
      cases. The average values of the distances between the GPF and the oral surfaces
      of the maxillary third molar, the medio-palatine suture, the posterior margin of
      the hard palate, the pterygoid hamulus and the pterygo-maxillary suture were 11.0
      (SD 1.5), 14.5 (SD 0.8), 4.4 (SD 1.1), 12.0 (SD 1.8) and 10.5 mm (SD 1.3),
      respectively. CONCLUSIONS: A thorough knowledge of GPF's various positions may
      assist the clinicians in providing improved surgical techniques in the area.

PMID- 24322028
TI  - Effect of diet and omega-3 fatty acids in NAFLD.
AB  - Nonalcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis to
      steatohepatitis (NASH) and cirrhosis. The aim of this study is to test beneficial
      effects of omega-3 fatty acids (DHA 130 mg, EPA 25 mg) treatment in NAFLD, in a
      mouse model of non-alcoholic fatty liver disease. As pretreatment, 50 mice were
      fed for one month with a high-fat diet to induce NAFLD. Then, the mice were
      divided in different groups according to diet (normo- or hypercaloric), with and
      without treatment with omega-3 fatty acids, for another month, forming the post
      treatment group. The liver and blood samples were collected for biochemical and
      histopathological analysis. Biochemical parameters including: glycemia, total
      cholesterol, triglycerides, uric acid, albumin, total plasma antioxidant capacity
      (TEAC) was measured in serum. Glutathione (GSH), total thiols and
      malonyldialdehyde (MDA) were determined in mouse liver homogenates. Mice from
      post-treatment group, on hypercaloric diet with or without omega-3 fatty acids
      treatment, had medium hepatopathy (granular and vacuolar degeneration of the
      hepatocytes) and hypertriglyceridemia. Omega-3 fatty acid treatment lowered the
      rise of triglycerides (p<0.03), glycemia (p<0.01) and cholesterol (p<0.02) in
      serum and MDA level of the liver (p<0.05). Mice from post-treatment group, on
      normocaloric diet with or without omega-3 fatty acid had different
      histopathological and biochemical results. Those with normocaloric/normolipidic
      diet and omega-3 fatty acids treatment had reversed liver histopathological
      results from NASH to normal aspect and had the best metabolic parameters results.
      In conclusion, omega-3 fatty acids treatment associated with a
      normocaloric/normolipidic diet has hepatoprotective action in nonalcoholic fatty
      liver disease.

PMID- 24322029
TI  - In vivo behavior of surface modified Ti6Al7Nb alloys used in selective laser
      melting for custom-made implants. A preliminary study.
AB  - The objectives of this study were to test the biocompatibility and to evaluate
      the osseointegration of Titanium-Aluminum-Niobium (Ti6Al7Nb) alloy used in the
      manufacturing of personalized implants with selective laser melting (SLM)
      technology and to compare the growth viability of osteoblastic-like cells on
      different Ti6Al7Nb alloy samples (plain, coated with hydroxyapatite or SiO2-TiO2)
      implanted into the cranial bone of Wistar rats. In terms of biocompatibility, the
      cone-beam computer-tomography head scans taken at the moment of sacrifice of each
      group (one, two and three months) showed no implant displacement, no osteolysis
      and no liquid collection around the implants. At one month, around all types of
      implants new bone formation was noticed, although around the plain Ti6Al7Nb
      implant a large amount of powder debris was present. Still, no inflammatory
      reaction was seen. At two months, the distance between the implants and the
      calvarial bone margins diminished. A thin layer of fibrous tissue was noticed
      around the Ti6Al7Nb implant coated with hydroxyapatite but no bone contact was
      achieved. In the group sacrificed at three months there was still no bone
      contact, but noticeable were the SiO2-TiO2. In the group sacrificed at three
      months SiO2-TiO2 particles detached from the implant and completely integrated in
      the tissue were noticeable. All results suggested that the Ti6Al7Nb alloy with or
      without infiltration is well biologically tolerated. 

PMID- 24322030
TI  - The process of ageing reflected by histological changes in the skin.
AB  - Structural and functional alterations, as well as changes occurring in the aspect
      of the skin during the ageing process, are due to some complex mechanisms,
      determined by intrinsic and extrinsic factors, which act synergistically. This
      study aims to analyze the histological changes of collagen and elastic fibers and
      of skin vasculature that occur in time, during the process of ageing. Fragments
      of skin have been collected from subjects of both sexes and of different ages,
      totaling 121 samples from different body regions. The following stains were used:
      Modified Goldner's Masson trichrome, Ferric Orcein-Hematoxylin and the combined
      stains Orcein-Goldner's trichrome. As the process of ageing advances, collagen
      fibers become thinner and change their aspect; at advanced age, the lysis of
      collagen fibers and their thickening in the deep dermis is present, as they
      become more fibrous. Elastic fibers show the tendency of fragmentation at more
      advanced age, gradually change their tinctorial affinity and reduce in amount; in
      the deep dermis, they tend to thicken progressively, in the presence of discrete
      elastolysis processes that evolve steadily and irreversibly. Thus, processes of
      elastic fibers degeneration and lysis run faster by comparison with those of
      collagen fibers degeneration. With ageing, a progressive reduction of dermis
      vasculature is present, due to a reduction in the number and size of vascular
      vessels, which is in its turn associated with the progressive alterations of
      vascular walls components, changes that advance until the function of the vessel
      ceases. 

PMID- 24322031
TI  - Gastric eosinophilia--clinical and morphological correlations.
AB  - Eosinophils of the gastrointestinal tract are involved in the host immune
      response that occurs in the presence of the pathogens in the digestive lumen,
      taking part in maintaining the homeostasis of the gastrointestinal epithelium.
      Their involvement in inflammatory processes of chronic gastritis is less known.
      In our study, we identified the presence of eosinophils in chorion gastric mucosa
      (lamina propria) in over 34% of chronic gastritis. Eosinophils were more numerous
      in atrophic gastritis with intestinal metaplasia. More than 65% of chronic
      gastritis associated with Helicobacter pylori also had eosinophils in the gastric
      mucosa. 

PMID- 24322032
TI  - Age influence on periodontal tissues: a histological study.
AB  - Oral mucosa becomes thinner, smooth and looses stippling aspect with aging. From
      histological standpoint appears: narrowing and alteration of gingival epithelium,
      modification of epithelial-connective interface and decreasing of keratinization.
      However, it cannot be detected significant histological alterations in size,
      shape or arrangement of epithelial cells that could be endorsed to aging process.
      Histological studies indicate: decreasing of keratinization, regressive changes
      in epithelium and fibrosis in underlying connective tissue. Parakeratosis is
      frequent with aging because of microtraumas, in many cases is expression of
      permanent inflammation. 

PMID- 24322034
TI  - A histological analysis of gingival condition associated with orthodontic
      treatment.
AB  - The aim of this histological study was to analyze the gingival reaction to fixed
      orthodontic appliances. Gingival specimens were obtained with minimal trauma from
      11 patients treated with fixed appliances in different intervals during the
      orthodontic treatment, including post-treatment periods. Serial sections were
      stained with Hematoxylin-Eosin. T- and B-cells were identified by specific
      antibodies, using a double staining technique with Avidin-Biotin method.
      Histological observations demonstrated and confirmed the presence of gingivitis
      during orthodontic treatment. According to the usual histological evaluation, the
      biopsies revealed the presence of hyperplastic chronic inflammatory changes from
      mild to moderate severity. The lack of rapid increase of CD20+ cells demonstrated
      that the gingival inflammation did not cause overall tissue destruction. 

PMID- 24322033
TI  - Correlation between histopathological aspects of periodontitis and biochemical
      changes of oxidative stress.
AB  - PURPOSE: The aim of this paper is to assess the histopathological changes and the
      condition of oxidative stress in the saliva of the patients with periodontal
      disease. MATERIALS AND METHODS: We have carried out our research on two groups of
      patients with periodontitis (a group of 16 patients with stage I periodontitis
      and a group of 16 patients with stage II periodontitis), who we have compared,
      using samples of saliva and serum, to a group of 15 volunteers without any dental
      restorations. To dose MDA, we used thiobarbituric acid method and for
      determination of ceruloplasmin the Ravin's method. For histopathological
      examination, the periodontal fragments were immediately underwent for fixation in
      10% neutral formalin solution and then, they were included in paraffin using the
      conventional histological technique. RESULTS: The group of patients with stage II
      periodontitis presented lower values of salivary MDA compared to the group of
      patients with stage I periodontitis. Patients with stage I periodontitis
      presented a significantly increased concentration of MDA in the serum compared to
      the control group, but considerably lower concentrations compared to patients
      with stage II periodontitis. The values of serum ceruloplasmin do not present
      statistically important changes in patients with stage I periodontitis compared
      to those suffering from stage II periodontitis and to those from the group
      control. CONCLUSIONS: MDA is not a product of blood filtration as the
      concentration of MDA in the bloodstream is bigger than in the saliva. Tissue
      changes and biochemical aspects are strongly connected. Removing dental plaque
      can prevent oral infections.

PMID- 24322035
TI  - Lichen planus secondary complications associated with the use of biologic therapy
      for rheumatoid arthritis.
AB  - OBJECTIVES: Biologic therapy such as Etanercept, which is a tumor necrosis factor
      alpha (TNF-alpha) inhibitor, has been extensively used as election therapy in
      rheumatoid arthritis. The purpose of this case presentation was to inform about
      the possibility that lichen planus lesions could potentially become complicated
      by secondary infections in patients treated with Etanercept. Furthermore, we
      aimed at analyzing if the complication of the cutaneous lesion was coincidental
      or it was due to the immunosuppressive systemic therapy, and whether the infected
      lesion would respond to antibiotic therapy. CASE SUMMARY: The patient was a 59
      year-old woman with rheumatoid arthritis and that have had lichen planus lesions
      for approximately 25 years. Only recently, she had been received
      immunosuppressive therapy (Etanercept and Methotrexate). Further on, the lichen
      planus flared up with a secondary infection determined by a Methicillin-sensitive
      Staphylococcus aureus. Uncommon myocardial complications were also characteristic
      of this case. RESULTS: While a case report described already the appearance of
      lichen planus following Etanercept therapy (Battistella M et al., 2008), the
      possibility that the lesion could become secondary complicated following this
      therapy was never reported before, according to our knowledge. Additionally, we
      describe in this case the interplay between Etanercept therapy and hypertrophic
      cardiomyopathy. CONCLUSIONS: Our case is not a lichen planus induced by
      Etanercept, but it is aggravated and secondary infected with Methicillin
      sensitive Staphylococcus during the therapy. The additional cardiac complication
      (hypertrophic cardiomyopathy) may represent solely an evolutive sign of
      rheumatoid arthritis and therefore not influenced by Etanercept.

PMID- 24322036
TI  - Sudden cardiac death due to triple myocardial bridging associated with atypical
      coronary topography.
AB  - Myocardial bridging (MB) is defined as the presence of an intramural course of a
      coronary artery, most likely caused by a defect in resorption of the musculature
      that encircles the epicardial arteries during morphogenesis. We present a case of
      the young man who died suddenly while playing professional football and whose
      cause of death was acute myocardial infarction associated with multiple
      myocardial bridges (1.8 cm on the anterior interventricular artery, 1.3 cm on the
      circumflex artery, and an intramyocardial trajectory of the posterior
      interventricular artery), and discuss the causes of death and possible
      consequences of this pathology. 

PMID- 24322037
TI  - Non-keratinizing undifferentiated carcinoma of the nasopharynx.
AB  - Nasopharyngeal carcinoma is the predominant tumor type arising in the nasopharynx
      with cervical lymph nodes present in 60-90% of all cases at the time of
      presentation. The most frequent pathological varieties include squamous cell
      carcinoma well-differentiated keratinizing, moderately differentiated non
      keratinizing and an undifferentiated type. We present a case of non-keratinizing
      undifferentiated carcinoma of the nasopharynx with parapharyngeal and middle
      cranial fossa space involvement in an 18-year-old male who has been admitted in
      our hospital for recurrent right ear otitis media. Symptoms consisted in mild
      conductive hearing loss, trigeminal V2 nerve anesthesia, right ear tinnitus, mild
      dysphagia, mild dysphonia, right hypoglossal nerve paralysis and right Claude
      Bernard-Horner's syndrome. Clinical examination revealed no lymph node masses,
      chest X-ray corresponding to a normal thoracic image. Cranial contrast enhanced
      CT scan showed a non-homogenous mass of 5.4/4.5/5.5 cm from the level of the
      right rhinopharyngeal wall, extending in the right parapharyngeal space, invading
      the right middle cranial fossa. Cranial MRI with contrast enhancement revealed a
      rhino- and parapharyngeal mass of 5.5/4.6/5.3 cm with intracerebral extension in
      the right cavernous sinus, right internal carotid artery being engulfed by the
      tumor mass with partial compression. Several lymph node masses of 1.7/1.2 cm were
      also revealed. We performed rhinopharyngeal biopsy, right tympanotomy and grommet
      tube insertion. The tissue specimens were processed with routine histological
      technique. Subsequent immunohistochemical reactions for pan-cytokeratin AE1/AE3
      and leukocytes common antigen were performed. The histological examination of
      routine stained slides showed that malignant tumor cells had a syncytial pattern
      of growth in a background of small lymphocytes. The positivity of tumor cells for
      pan-cytokeratin established the final diagnosis of non-keratinizing
      undifferentiated carcinoma. The age of onset, the clinical signs and symptoms and
      minimum involvement of lymph nodes represents the particular aspects of the case.

PMID- 24322038
TI  - Combination of six variations in a single arm.
AB  - Variations on the neuromuscular structures of the upper limb reflect the complex
      development of that region. Many of them may be important during surgical and/or
      diagnostic procedures; however, some of them are of academic interest. Here we
      report a case of six neuromuscular variations in a single upper limb. During
      routine educational dissection for the undergraduate medical students at the
      Department of Anatomy, Faculty of Medicine, Hacettepe University, Ankara, Turkey,
      we came across six variations on the left upper limb of a 43-year-old well-built
      male cadaver. We conformed to the steps described in Grant's Dissector during the
      dissection, and photographed the case with a Nikon Coolpix camera. The biceps
      brachii showed an accessory head that originated from the tendon of pectoralis
      major, ran downwards superficial to the long head and joined the distal 1/3 of
      the muscle mass. A thin muscle band accompanying the lateral side of the
      pectoralis major was identified as pectoralis quartus. It was originated from the
      sixth rib and inserted to the coracoid process. The coracobrachialis was double
      headed having a common origin from the coracoid process, separating into two
      after a short course and joining again at the middle level of the arm.
      Musculocutaneous nerve did not pierce the coracobrachialis. Instead, it ran
      beneath the two bellies of the muscle. The lateral cord of the brachial plexus
      passed between the two bellies of coracobrachialis; then divided into
      musculocutaneous nerve and the lateral root of the median nerve at a lower level
      than usual. The right upper limb showed no variations. The variations described
      here maybe commonly encountered individually; however, the combination of six of
      them in a single arm is previously unreported.

PMID- 24322039
TI  - Axillary basal cell carcinoma--a rare form of a frequent kind of carcinoma.
AB  - Basal cell carcinoma (BCC) is the most common cutaneous cancer. It seems that the
      most important prognostic factor is exposure to ultraviolet radiation (solar and
      artificial), correlated with other factors as well. In this article, we aimed to
      review basal cell carcinoma located in the axilla, referring to cases from our
      hospital. Axillary location of BCC is rare, with a very low number of cases
      quoted in the literature, compared to the high prevalence of basal cell carcinoma
      in the general population. During a period of two years, we detected only four
      cases of axillary basal cell carcinoma out of a total number of 921 cases
      diagnosed as BCC. We were interested in identifying certain factors involved in
      causing BCC, post-excision clinical evolution, histological type and
      aggressiveness of axillary basal cell carcinoma. Therefore, we quantified
      objectively the tumor and stromal expression of some immunological markers like:
      metalloproteinases MMP1, 3, 11, Ber-EP4 and Ki67. Histological types of tumors
      investigated here belong to the category of non-aggressive BCC, namely as nodular
      and superficial, although Ki67 index is greater than the average reported in the
      literature for this type of tumor. MMPs exhibited increased expression in tumors
      and stromal compartments, especially at the tumor invasion front, and was not
      associated with tumor ulceration or surrounding tissue remodeling-related
      changes. Our results confirm the literature data concerning the involvement of
      MMPs in BCC progression, whatever the tumor location is. 

PMID- 24322040
TI  - Modifications of the marginal paradentium to a case of Angle Class III/1
      malocclusion.
AB  - Angle Class III malocclusions are not so frequently met but they raise big
      problems of treatment. The analyzed case represents a 14-year-old patient that
      came to the dental consulting room with an Angle Class III malocclusion
      determined by the excess of the somatotropic pituitary hormone and a gingival
      hyperplasia more emphasized at the level of inferior frontal teeth. The patient
      followed a fixed appliance treatment, the straight-wire technique. All along the
      treatment and after it, the hyperplasia and the gingival inflammation not only
      maintained but they even got worse. Thus, an improper hygiene associated with a
      severe Angle Class III malocclusion maintains and aggravates the gingivitis. The
      histological and immunohistochemical study of the gingiva revealed important
      epithelial modifications that led to an epithelial hypertrophy with a tendency
      toward acanthosis and to severe epithelial erosions. An inflammatory chronic
      process (rich in lymphocytes, plasma cells and macrophages full of angiogenesis
      vessels) and an intense reaction of the fibroblastic cells appeared in the
      gingival corium. 

PMID- 24322041
TI  - A rare case of watermelon stomach in woman with continuous ambulatory peritoneal
      dialysis and systemic lupus erythematosus.
AB  - We report a case of a 42-year-old woman with systemic lupus erythematosus and
      chronic kidney disease stage 5 undergoing continuous ambulatory peritoneal
      dialysis, presenting asthenia, dizziness, abdominal pain and small efforts
      dyspnea. After a complete physical and clinical examination, including laboratory
      tests, esophagogastroduodenal endoscopy and gastric lesions biopsy, she was
      diagnosed with gastric antral vascular ectasia. We are facing a rare case of
      antral vascular ectasia in a patient associating both chronic kidney disease and
      autoimmune disease. 

PMID- 24322042
TI  - Particular aspects in endoscopic surgery for juvenile nasopharyngeal
      angiofibromas. Case reports and review of literature.
AB  - Juvenile nasopharyngeal angiofibromas (JNA) are rare, benign, highly vascular
      tumors which appear in proximity to the sphenopalatine foramen. The tumor arises
      most commonly in adolescent males suggesting that in could be hormonally
      responsive. Although it is histologically benign, it has a high destructive
      potential and a high grade of recurrence. It is a fibrous vascular tumor with
      vascular sources from branches of the external or internal carotid arteries.
      Modern treatment of JNA includes surgery and also radiotherapy, chemotherapy and
      hormone therapy. This paper presents two cases from the eight of our clinic's
      experience, with morphological features which made their treatment challenging. 

PMID- 24322043
TI  - Ossification of the choroid: three clinical cases and literature review of the
      pathogenesis of intraocular ossification.
AB  - OBJECTIVE: A presentation of the clinical and pathogenic aspects of choroidal
      ossification. CASES PRESENTATION: We report three clinical cases of choroidal
      ossification: choroidal osteoma, ossified choroidal hemangioma and total
      ossification of the choroid. The three patients underwent complete eye
      examination. The optical microscopy of a sample of ossified choroidal tissue
      revealed a spongy, osseous structure consisting of circular osseous lamellae,
      osteocytes, canaliculi and adipose tissue with microfoci of calcification.
      DISCUSSION: Choroidal ossification is characterized by reduced frequency of
      occurrence, accessible clinical diagnosis, and unspecified pathogenesis. Several
      of the factors identified in the pathogenesis of intraocular ossification may
      play a role in the ossification of the choroid: chronic inflammatory cells, bone
      morphogenetic proteins, growth factors and mesenchymal stem cells. In addition to
      these factors, pericytes have a special role in the pathogenesis of choroidal
      ossification. Under the influence of bone morphogenetic proteins and growth
      factors, mesenchymal stem cells differentiate into osteoblasts. They secrete bone
      matrix (osteoid), whose regeneration and remodeling lead to the formation of bone
      tissue. The spongy bone structure of choroidal tissue points to a model of
      endoconjunctive/desmal ossification. CONCLUSIONS: The knowledge of the clinical
      aspect of ossification of the choroids is required for the differential diagnosis
      with the posterior pole affections, and also for the prevention and treatment of
      secondary complications.

PMID- 24322044
TI  - Dens invaginatus in an impacted mesiodens: a morphological study.
AB  - Dens invaginatus (DI) is a dental anomaly originated from invagination of the
      enamel organ into the dental papilla, during odontogenesis. DI may be associated
      with other abnormalities such as dysmorphic mesiodens, and this unusual condition
      may be detected by chance on the conventional radiography. However, the three
      dimensional nature and the exact morphological patterns of DI are impossible to
      appreciate from this method. We present a morphological study of impacted
      mesiodens in a 9-year-old girl, which the three coronal invaginations were
      detected only by Cone-Beam Computed Tomography (CBCT) in the pre-surgical
      examination. CBCT, radiographic and microscopic reproductions allow transfer of
      images to facilitate cooperation of working groups, examination as well as for
      teaching purposes. 

PMID- 24322045
TI  - Littoral cell angioma of the spleen--a surprising cause of anemia.
AB  - Littoral cell angioma is a rare tumor of the spleen, usually being considered
      benign and typically discovered incidentally. There are three different
      modalities of presentation: tumoral splenomegaly, long-standing iron deficient
      anemia or thrombocytopenia due to hypersplenism. However, some of its
      manifestations could generate the suspicion of a lymphoma or other more serious
      condition. We present the case of a 46-year-old man with splenomegaly and iron
      deficiency anemia. The tumor affected the whole spleen, which was surgically
      removed. The histopathological examination, together with immunophenotyping,
      established the diagnosis. Six months after the procedure, the patient is in very
      good condition. Several differential diagnoses were discussed, as well as the
      prognostic factors. The case illustrates a rare cause of anemia and the
      importance of pathology in uncovering such unusual causes for this. 

PMID- 24322046
TI  - Giant maxillary cyst with intrasinusal evolution.
AB  - Giant maxillary cysts deserve one's attention, mainly because of all the
      complication they can originate, such as facial aesthetic changes, jaw fractures,
      infections and occasional but the most severe one the neoplasia of its
      epithelium. Here we present the case of a 51-year-old man who was sent to the
      Clinic of Oral and Maxillofacial Surgery of Timisoara, Romania, because of a
      facial asymmetry due to the hyper-dimension of the right superior genian and
      labial region, consecutive to the volume growth of the subjacent alveolar
      process. The clinical and paraclinical investigations, especially the fine-needle
      aspiration and the 3D imagistic investigation, most likely lead to the diagnosis
      of maxillary cyst with intrasinusal evolution, the lesion being caused by the
      untreated teeth of the superior right hemiarcade. The surgery was performed in
      general anesthesia and consisted of a cystectomy and the curettage of the right
      maxillary sinus, followed by the restoration of alveolar process with the help of
      bone graft materials. The histopathological examination of the lesion confirmed
      the diagnosis of maxillary radicular cyst. This case shows the frequently
      asimptomatic and long-term evolution of maxillary cysts, their growing volume
      causing massive bone destructions and affections of the neighboring anatomic
      structures. 

PMID- 24322047
TI  - Accessory cleido-occipitalis muscle: case report and review of the literature.
AB  - An aberrant muscular fascicle, the so-called "accessory cleido-occipital muscle",
      originated from the anterior border of the cleido-occipital portion of the right
      trapezius muscle, was detected during a routine dissection of a female cadaver.
      The aforementioned muscular bundle coursing in the posterior cervical triangle,
      almost parallel to the anterior border of the trapezius muscle, inserted
      ultimately to the clavicle's medial third. In addition, prior to its insertion,
      the muscle provided a fibrous arch attached to the midportion of clavicle,
      overlying the main trunk of supraclavicular nerves. We noted that during
      abduction of the right arm, the fibrous arch entrapped the supraclavicular nerve
      trunk, presumably leading to sensory disturbances in nerve's area distribution.
      We review the relative restricted data in the available literature concerning
      that muscular variant and elucidate its importance during differential diagnosis
      of a mass and surgical exploration of the posterior cervical triangle. 

PMID- 24322048
TI  - Cardiac metastasis and tumor embolism in a patient with adenocarcinoma of the
      colon presenting with paraneoplastic polymyositis.
AB  - Colorectal cancer usually presents with alterations in the bowel habit. Less
      commonly, the presenting symptoms may be part of a paraneoplastic syndrome.
      Metastasis can occur by lymphatic or hematogenous spread, most frequently to the
      lungs and liver. We present the case of a 56-year-old man admitted with
      paraneoplastic polymyositis due to a poorly differentiated colon adenocarcinoma.
      The evolution was unfavorable with death on the 19th day following admission due
      to pulmonary thromboembolism and subsequent pulmonary edema. Autopsy showed
      micrometastases with lymphatic and venous emboli to the heart, liver, kidney,
      adrenal gland and lung. The case highlights the diversity of manifestation that
      can occur in a colon adenocarcinoma. 

PMID- 24322049
TI  - The squamous cell carcinoma at the level of the cephalic extremity:
      epidemiological, clinical and histopathological aspects.
AB  - Malignant tumors represent one of the most important medical problems, due to the
      increased mortality rate, life quality alteration, and the lack of a curable
      treatment. Skin neoplasm ranks first most frequent top primary tumor, summing a
      higher percentage than any other neoplastic location. It is also known, the fact
      that, in our country, gastric adenocarcinoma represents the most encountered
      tumor of the digestive tube. Our case, male, 49-year-old, comes from a rural
      area, was diagnosed with and surgically treated, within one year, for gastric
      adenocarcinoma (intestinal type gastric carcinoma) and squamous cell carcinoma
      (at the level of the lower lip). A high number of etiologic agents are associated
      with different risks in developing a carcinoma with squamous cells at the level
      of the head and the neck, and a gastric carcinoma (our patient is known to suffer
      from gastric ulcer and Helicobacter pylori, for more than 20 years, and he is a
      chronic consumer of alcohol and nicotine). 

PMID- 24322050
TI  - Comment to the Letter to the Editor: Does "signet-ring stromal tumor" exist? In
      reply to the comments by Teresa Pusiol et al.

PMID- 24322051
TI  - Letter to the Editor. Attitude of Romanian medicine students towards plagiarism.

PMID- 24322052
TI  - Differentiation of somatic cells in the ovariuteri of the apoikogenic scorpion
      Euscorpius italicus (Chelicerata, Scorpiones, Euscorpiidae).
AB  - In apoikogenic scorpions, growing oocytes protrude from the gonad (ovariuterus)
      and develop in follicles exposed to the mesosomal (i.e. hemocoelic) cavity.
      During subsequent stages of oogenesis (previtellogenesis and vitellogenesis), the
      follicles are connected to the gonad surface by prominent somatic stalks. The aim
      of our study was to analyze the origin, structure and functioning of somatic
      cells accompanying protruding oocytes. We show that these cells differentiate
      into two morphologically distinct subpopulations: the follicular cells and stalk
      cells. The follicular cells gather on the hemocoelic (i.e. facing the hemocoel)
      surface of the oocyte, where they constitute a cuboidal epithelium. The
      arrangement of the follicular cells on the oocyte surface is not uniform;
      moreover, the actin cytoskeleton of these cells undergoes significant
      modifications during oocyte growth. During initial stages of the stalk formation
      the stalk cells elongate and form F-actin rich cytoplasmic processes by which the
      stalk cells are tightly connected to each other. Additionally, the stalk cells
      develop microvilli directed towards the growing oocyte. Our findings indicate
      that the follicular cells covering hemocoelic surfaces of the oocyte and the
      stalk cells represent two distinct subpopulations of epithelial cells, which
      differ in morphology, behavior and function. 

PMID- 24322053
TI  - Inhaled NO prevents hyperoxia-induced white matter damage in neonatal rats.
AB  - White matter damage (WMD) and bronchopulmonary dysplasia (BPD) are the two main
      complications occurring in very preterm infants. Inhaled nitric oxide (iNO) has
      been proposed to promote alveolarization in the developing lung, and we have
      reported that iNO promotes myelination and induces neuroprotection in neonatal
      rats with excitotoxic brain damage. Our hypothesis is that, in addition to its
      pulmonary effects, iNO may be neuroprotective in rat pups exposed to hyperoxia.
      To test this hypothesis, we exposed rat pups to hyperoxia, and we assessed the
      impact of iNO on WMD and BPD. Rat pups were exposed to either hyperoxia (80%
      FiO2) or to normoxia for 8 days. Both groups received iNO (5 ppm) or air. We
      assessed the neurological and pulmonary effects of iNO in hyperoxia-injured rat
      pups using histological, molecular and behavioral approaches. iNO significantly
      attenuated the severity of hyperoxia-induced WMD induced in neonatal rats.
      Specifically, iNO decreased white matter inflammation, cell death, and enhanced
      the density of proliferating oligodendrocytes and oligodendroglial maturation.
      Furthermore, iNO triggered an early upregulation of P27kip1 and brain-derived
      growth factor (BDNF). Whereas hyperoxia disrupted early associative abilities,
      iNO treatment maintained learning scores to a level similar to that of control
      pups. In contrast to its marked neuroprotective effects, iNO induced only small
      and transient improvements of BPD. These findings suggest that iNO exposure at
      low doses is specifically neuroprotective in an animal model combining injuries
      of the developing lung and brain that mimicked BPD and WMD in preterm infants.

PMID- 24322054
TI  - Interplay of PKA and Rac: fine-tuning of Rac localization and signaling.
AB  - Cellular membrane receptors sense environmental changes and relay the reshaped
      signal through spatially and temporally organized protein-protein interactions
      (PPI). Many of such PPI are transient and occur in a certain cell-dependent
      context. Molecular switches such as kinases and GTPases are engaged in versatile
      PPI. Recently, we have identified dynamic interaction and reciprocal regulation
      of cAMP-dependent protein kinase A (PKA) and Rho-GTPase Rac signaling. We
      demonstrated that GTP-activated Rac acts as a dual kinase-tuning scaffold for p21
      activated kinase (PAK) and PKA activities. We showed that receptor-triggered PKA
      trans-phosphorylation of GTP-Rac-organized PAK contributes to elevations of
      nuclear Erk1/2 signaling and proliferation. We discuss these recent observations
      and we provide additional insights how the cAMP-PKA axis might also participate
      in the regulation of Rac localization. 

PMID- 24322056
TI  - Post-mortem genetic testing in a family with long-QT syndrome and hypertrophic
      cardiomyopathy.
AB  - Pediatric sudden unexplained deaths are rare and tragic events that should be
      evaluated with all the tools available to the medical community. The current
      state of genetic testing is an excellent resource that improves our ability to
      diagnose cardiovascular disorders that can lead to sudden cardiac arrest. Post
      mortem genetic testing is not typically a covered benefit of health insurance and
      may not be offered to families in the setting of a negative autopsy. This unusual
      case includes two separate cardiovascular disorders that highlight the use of
      genetic testing and its role in diagnosis, screening, and risk stratification.
      The insurance company's decision to cover post-mortem testing demonstrated both
      compassion as well as an understanding of the long-term cost effectiveness. 

PMID- 24322059
TI  - Relationships between metals exposure and epidemiological parameters of two
      pathogens in urban pigeons.
AB  - Human activities often generate or increase concentration of chemical compounds
      including pesticides, hydrocarbons and metals that can potentially affect
      ecological interactions. We found that elevated levels of zinc in pigeon feathers
      were associated with both low prevalence of Chlamydiaceae (ornithosis disease)
      and low intensity of blood pathogens (Haemosporidian parasites). In contrast,
      high levels of lead in pigeon feathers were associated with high blood pathogens
      intensities. Our results suggest that metals linked to human activities in cities
      such as zinc and lead may play a significant role in the ecology of host-parasite
      interactions and could potentially affect the epidemiology of diseases in the
      urban environment.

PMID- 24322055
TI  - Antifibrotic response of cardiac fibroblasts in hypertensive hearts through
      enhanced TIMP-1 expression by basic fibroblast growth factor.
AB  - BACKGROUND: Cardiac fibroblasts (CFs) play a pivotal role in the development of
      myocardial fibrosis. We previously demonstrated that direct injection of basic
      fibroblast growth factor (bFGF) into the hypertensive Dahl salt-sensitive (DS)
      rat heart prevented systolic dysfunction and left ventricular dilation
      effectively. However, the precise role played by bFGF in fibrotic response of CFs
      remains unclear. We suggested potential effects of bFGF on the fibrotic response
      of CFs in vitro. METHODS AND RESULTS: Histopathologic assessment of cardiac
      fibrosis demonstrated a marked decline in the extent of perivascular and
      interstitial fibrosis in bFGF-injected hypertensive DS rat hearts. CFs harvested
      from the hearts of noninjected DS rats demonstrated a significantly increased
      messenger RNA (mRNA) expression of matrix metalloproteinase (MMP)-2, MMP-9, and
      both collagen I and III. In contrast, bFGF treatment in the CFs induced a marked
      increase in tissue inhibitor of MMP (TIMP)-1 expression and a marked decline in
      MMP-9 activation. bFGF also induced a decline in alpha-smooth muscle actin and
      collagen I and III mRNA expression in the CFs accompanied by inhibited
      differentiation of CFs into myofibroblasts. Small interfering RNA targeting FGF
      receptor 1 confirmed a specific interference of the mRNA expression changes
      elicited by bFGF. In vivo examination confirmed many TIMP-1-positive CFs in
      perivascular spaces of bFGF-injected hearts. CONCLUSIONS: Up-regulated TIMP-1
      expression and down-regulated MMP-9 activation by bFGF in CFs could prevent
      excessive ECM degradation and collagen deposition in perivascular spaces
      effectively, leading to prevention of cardiac fibrosis during hypertensive heart
      failure. SUMMARY: Cardiac fibroblasts (CFs) play a pivotal role in myocardial
      fibrosis. The precise role of CFs in fibrotic response played by growth factors
      remains unclear. Our results indicates that basic fibroblast growth factor could
      up-regulate TIMP-1 expression and down-regulate MMP-9 activation in CFs in
      perivascular spaces, leading to inhibited progression of cardiac fibrosis during
      hypertensive heart failure.

PMID- 24322061
TI  - The Arizona Sexual Experiences Scale: a validity and reliability assessment of
      the Thai translation (ASEX-Thai) in Parkinson's disease.
AB  - INTRODUCTION: Cultural sensitivities tend to limit assessments of sexual
      dysfunction (SD) in Parkinson's disease (PD). OBJECTIVE: To assess the validity
      and reliability of the Thai translation (ASEX-Thai) of the Arizona Sexual
      Experiences Scale (ASEX). METHOD: The validity and reliability of ASEX-Thai were
      assessed with a random sample of 40 PD patients. Back translation and cross
      cultural modifications assured content validity. Criterion validity used DSM-IV
      TR criteria and receiver operating characteristics (ROC) analysis was calculated
      for cutoff points plus sensitivity and specificity. Internal consistency was
      assessed with Cronbach's alpha coefficient. Test-retest reliability was assessed
      by Pearson's correlation at baseline and at a 2-month follow-up. RESULT:
      Criterion validity was conducted with a positive correlation between the clinical
      diagnosis of SD and DSM-IV-TR (r = 0.601; p < 0.001). The ROC analysis
      differentiated between SD and non-SD patients (p < 0.001). The cutoff point of
      ASEX-Thai at >=16 points effectively screened for SD (sensitivity 96.2%,
      specificity 92.9%). Reliability was documented with the Cronbach's alpha of all
      items at baseline and at a 2-month follow-up with values of 0.948 and 0.962
      respectively. The Pearson's correlation also showed highly significant test
      retest reliability [Item 1 (r = 0.959, p < 0.001), Item 2 (r = 0.914, p < 0.001),
      Item 3 (r = 0.944, p < 0.001), Item 4 (r = 0.992, p < 0.001), Item 5 (r = 0.930,
      p < 0.001), and total ASEX-Thai score (r = 0.883, p < 0.001)]. CONCLUSION: ASEX
      Thai is a valid and reliable instrument for the assessment of sexual dysfunction
      in Thai PD patients.

PMID- 24322060
TI  - Youth problem behaviors 8 years after implementing the communities that care
      prevention system: a community-randomized trial.
AB  - IMPORTANCE: Community-based efforts to prevent adolescent problem behaviors are
      essential to promote public health and achieve collective impact community wide.
      OBJECTIVE To test whether the Communities That Care (CTC) prevention system
      reduced levels of risk and adolescent problem behaviors community wide 8 years
      after implementation of CTC. DESIGN, SETTING, AND PARTICIPANTS: A community
      randomized trial was performed in 24 small towns in 7 states, matched within
      state, assigned randomly to a control or intervention group in 2003. All fifth
      grade students attending public schools in study communities in 2003-2004 who
      received consent from their parents to participate (76.4% of the eligible
      population) were included. A panel of 4407 fifth graders was surveyed through
      12th grade, with 92.5% of the sample participating at the last follow-up.
      INTERVENTIONS: A coalition of community stakeholders received training and
      technical assistance to install CTC, used epidemiologic data to identify elevated
      risk factors and depressed protective factors for adolescent problem behaviors in
      the community, and implemented tested and effective programs for youths aged 10
      to 14 years as well as their families and schools to address their community's
      elevated risks. MAIN OUTCOMES AND MEASURES Levels of targeted risk; sustained
      abstinence, and cumulative incidence by grade 12; and current prevalence of
      tobacco, alcohol, and other drug use, delinquency, and violence in 12th grade.
      RESULTS: By spring of 12th grade, students in CTC communities were more likely
      than students in control communities to have abstained from any drug use
      (adjusted risk ratio [ARR] = 1.32; 95% CI, 1.06-1.63), drinking alcohol (ARR =
      1.31; 95% CI, 1.09-1.58), smoking cigarettes (ARR = 1.13; 95% CI, 1.01-1.27), and
      engaging in delinquency (ARR = 1.18; 95% CI, 1.03-1.36). They were also less
      likely to ever have committed a violent act (ARR = 0.86; 95% CI, 0.76-0.98).
      There were no significant differences by intervention group in targeted risks,
      the prevalence of past-month or past-year substance use, or past-year delinquency
      or violence. CONCLUSIONS AND RELEVANCE: Using the CTC system continued to prevent
      the initiation of adolescent problem behaviors through 12th grade, 8 years after
      implementation of CTC and 3 years after study-provided resources ended, but did
      not produce reductions in current levels of risk or current prevalence of problem
      behavior in 12th grade. TRIAL REGISTRATION clinicaltrials.gov Identifier:
      NCT01088542.

PMID- 24322062
TI  - A clinical approach towards smell loss in Parkinson's disease.
AB  - Impairment of olfaction is a characteristic feature of Parkinson's disease (PD).
      Recent data indicate that >90% of patients with PD are diagnosed with significant
      olfactory loss. The olfactory loss in PD has a bilateral and general character
      and all olfactory domains are involved. By clinical measurements, the olfactory
      deficit in PD is independent of disease severity and duration. Imaging studies
      however, point out that the olfactory impairment may be progressive in the early
      motor stages. Deficits in the sense of smell may precede clinical motor symptoms
      by years and can be used to assess the risk for developing PD in otherwise
      asymptomatic individuals. Numerous studies suggest that olfactory disturbances in
      PD may have diagnostic utility for the differentiation of PD from other movement
      disorders. This review summarizes the available information about the character
      of olfactory function in PD and possible therapeutic strategies. It indicates the
      advantageous use of olfactory probes as a contribution to early and differential
      diagnosis. 

PMID- 24322063
TI  - Can cognitive remediation improve mobility in patients with Parkinson's disease?
      Findings from a 12 week pilot study.
AB  - BACKGROUND: Patients with Parkinson's disease (PD) suffer from impaired gait and
      mobility. These changes in motor function have been associated with cognitive
      deficits that also commonly co-occur in PD, especially executive function (EF)
      and attention. OBJECTIVE: We hypothesized that a cognitive remediation program
      would enhance gait and mobility. METHODS: The 18 PD patients in this study were
      assessed at baseline and again one and four weeks after completion of a 12 week
      long, home-based computerized cognitive training program. Subjects were asked to
      "play" computer games designed to improve EF and attention for 30 minutes a day,
      three times per week for 12 weeks, while seated. The Timed Up and Go (TUG), gait
      speed, and stride time variability quantified mobility. A previously validated,
      computerized neuropsychological battery quantified global cognitive function and
      its sub-domains. RESULTS: Compared to pre-training values, global cognitive
      scores and time to complete the TUG significantly improved after the training.
      TUG components of turning speed and duration also improved. Other TUG components,
      gait speed, and variability did not change after training. CONCLUSIONS: These
      initial findings suggest that computerized cognitive training can improve
      cognitive function and has a beneficial carryover effect to certain aspects of
      mobility in patients with PD. Additional studies are required to replicate these
      findings and more fully assess the underlying mechanisms. Nonetheless, the
      present results underscore the motor-cognitive link in PD and suggest that
      computerized cognitive training may be applied as a therapeutic option to enhance
      mobility in patients with PD.

PMID- 24322064
TI  - Lateral-shearing, delay-dithering Mach-Zehnder interferometer for spatial
      coherence measurement.
AB  - An image-shearing interferometer of Mach-Zehnder type with corner cubes is
      introduced for the purpose of measuring spatial coherence at the output of
      inhomogeneous optical sources, such as multimode fibers (MMFs). One arm of the
      interferometer is modulated in optical delay to produce dynamic interference
      fringes. Fringe visibility and the two individual intensities are measured nearly
      simultaneously to allow direct calculation of the modulus of the complex degree
      of coherence as a function of the lateral shear between the two interferometer
      arms. Spatial degree of coherence is measured for a step-index MMF pumped with
      monochromatic and broadband optical sources. 

PMID- 24322065
TI  - En face optical coherence tomography of transient light response at photoreceptor
      outer segments in living frog eyecup.
AB  - This study was designed to test the feasibility of en face mapping of the
      transient intrinsic optical signal (IOS) response at photoreceptor outer segments
      and to assess the effect of spatial resolution on functional IOS imaging of
      retinal photoreceptors. A line-scan optical coherence tomography (LS-OCT) was
      constructed to achieve depth-resolved functional IOS imaging of living frog
      eyecups. Rapid en face OCT revealed transient IOS almost immediately (<3 ms)
      after the onset of visible light flashes at photoreceptor outer segments.
      Quantitative analysis indicated that the IOS kinetics may reflect dynamics of G
      protein binding and releasing in early phases of visual transduction, and high
      resolution is essential to differentiate positive and negative IOS changes in
      adjacent locations.

PMID- 24322066
TI  - In vivo x-ray luminescence tomographic imaging with single-view data.
AB  - X-ray luminescence computed tomography (XLCT) is a new molecular imaging
      modality. In this Letter, we first in vivo tomographically image the near-IR
      emitting nanophosphor (Gd<sub>2</sub>O<sub>3</sub>:Eu<sup>3+</sup>) in nude mice
      (N=2). In practically, incorporating the compressive sensing technique, the XLCT
      reconstruction is performed only using single-view data. The experimental results
      indicate that the single-view reconstruction is feasible to image XLCT in vivo.
      The location error is less than 1.5 mm. Further, the imaging time can be greatly
      reduced compared with previous XLCT systems. Therefore, it is suited for imaging
      fast distribution of x-ray-excitable nanophosphors within a biological object. 

PMID- 24322067
TI  - Widely tunable all-fiber optical parametric oscillator based on a photonic
      crystal fiber pumped by a picosecond ytterbium-doped fiber laser.
AB  - We report on a fully fiber-integrated widely tunable optical parametric
      oscillator based on a photonic crystal fiber pumped by a picosecond ytterbium
      doped fiber laser. The output wavelength of the oscillator can be continuously
      tuned from 898 to 1047 nm and from 1086 to 1277 nm, which is as wide as 340 nm.
      In particular, a larger Raman gain peak is simultaneously observed when the pump
      wavelength is far from the zero-dispersion wavelength in the normal-dispersion
      regime. The bandwidth of the output of the oscillator can be tuned by slightly
      adjusting the pump power.

PMID- 24322068
TI  - Hybrid lightwave subcarrier CATV/16-QAM/16-QAM OFDM transmission system.
AB  - A hybrid lightwave subcarrier CATV/16-QAM/16-QAM orthogonal frequency-division
      multiplexing (OFDM) transmission system employing light injection/optoelectronic
      feedback techniques and photonic crystal fiber (PCF) is proposed and
      demonstrated. Good performance of carrier-to-noise ratio (CNR), composite second
      order, and composite triple beat were obtained for the CATV band, and high CNR
      and low bit error rate values were achieved for the 16-QAM and 16-QAM OFDM bands
      over a combination of 80 km single-mode fiber (SMF) and 2.86 km PCF transport.

PMID- 24322069
TI  - Gigahertz to terahertz tunable all-optical single-side-band microwave generation
      via semiconductor optical amplifier gain engineering.
AB  - We propose and demonstrate a technique to generate low-noise broadly tunable
      single-side-band microwaves using cascaded semiconductor optical amplifiers
      (SOAs) using no RF bias. The proposed technique uses no RF components and is
      based on polarization-state controlled gain-induced four-wave mixing in SOAs.
      Microwave generation from 40 to 875 GHz with a line-width ~22 KHz is
      experimentally demonstrated.

PMID- 24322070
TI  - Controlling pulse delay by light and low magnetic fields: slow light in emerald
      induced by transient spectral hole-burning.
AB  - Slow light based on transient spectral hole-burning is reported for emerald,
      Be(3)Al(2)Si(6)O(18):Cr(3+). Experiments were conducted in pi polarization on the
      R(1)(+/- 3/2) line (E2 <- A(2)4) at 2.2 K in zero field and low magnetic fields
      B||c. The hole width was strongly dependent on B||c, and this allowed us to
      smoothly tune the pulse delay from 40 to 154 ns between zero field and B||c =
      15.2 mT. The latter corresponds to a group velocity of 16 km/s. Slow light in
      conjunction with a linear filter theory can be used as a powerful and accurate
      technique in time-resolved spectroscopy, e.g., to determine spectral hole-widths
      as a function of time.

PMID- 24322071
TI  - Multi-gigahertz picosecond optical parametric oscillator pumped by 80-MHz Yb
      fiber laser.
AB  - We report a multi-gigahertz (GHz) repetition-rate picosecond optical parametric
      oscillator (OPO) based on MgO:PPLN, synchronously pumped by a Yb-fiber laser
      operating at 80 MHz, where the multiplication of repetition frequency is achieved
      using fractional increment in the OPO cavity length. Using this simple technique,
      we achieve OPO operation up to the 88th harmonic of the pump laser frequency,
      corresponding to a repetition rate as high as 7 GHz. Deploying a 5% output
      coupler, we are able to extract up to 960 mW of average signal power at the
      fundamental with 600 mW at the 88th harmonic (7 GHz), using a pump power of 5.6
      W. The measured relative standard deviations of the fundamental and fifth
      harmonic signal power are recorded to be 1.6% and 3.5%, respectively, while the
      fundamental signal pulse duration is measured to be 18.4 ps.

PMID- 24322072
TI  - On-chip sensor for light direction detection.
AB  - We present an on-chip optical sensor capable of detecting the direction of
      incident light. No off-chip optical or mechanical components or modifications-
      for example, baffles, slit structures, mirrors, etc.--are needed. The sensor was
      implemented in a standard 0.5 MUm complementary metal-oxide semiconductor
      process. A pair of on-chip photodiodes separated by a metal "wall" (created by
      stacking all metal layers, contacts, and vias available in the process) is used
      to detect the direction of the incident light. This metal stack wall creates on
      chip shadowing to facilitate detection so that the two photodiodes produce
      different amounts of photocurrent. A model for this device is presented. The
      analysis indicts that the ratio of the difference of these two currents to the
      larger of the two currents has a linear relationship with the angle of the
      incident light. Moreover, we also demonstrate this ratio is almost independent of
      the incident light intensity. Test results verify these two conclusions and show
      good sensitivity to light direction and immunity to light intensity. An accuracy
      of 1.6 deg over a 100 deg range is achieved by the linear relationship.

PMID- 24322073
TI  - Optical coherence tomography-based micro-particle image velocimetry.
AB  - We present a new application of optical coherence tomography (OCT), widely used
      in biomedical imaging, to flow analysis in near-wall hydrodynamics for marine
      research. This unique capability, called OCT micro-particle image velocimetry,
      provides a high-resolution view of microscopic flow phenomena and measurement of
      flow statistics within the first millimeter of a boundary layer. The technique is
      demonstrated in a small flow cuvette and in a water tunnel. 

PMID- 24322074
TI  - Quasi-Bragg conditions in Thue-Morse dielectric multilayers.
AB  - The existence of quasi-Bragg conditions (QBCs) in Thue-Morse dielectric
      multilayers (TMDMs), based on high reflectance and large forbidden gap regions in
      its transmission spectra, is presented. In contrast to a single traditional Bragg
      condition (TBC) in periodic bilayers, there are three QBCs in TMDMs. The formula
      for each of these QBCs is derived. The results show that one of these QBCs just
      overlaps the TBC. However, a singular point with perfect transmission exists in
      this QBC at the quarter-wave stack, at which high reflection exists in the
      periodic bilayers. 

PMID- 24322075
TI  - Split-probe hybrid femtosecond/picosecond rotational CARS for time-domain
      measurement of S-branch Raman linewidths within a single laser shot.
AB  - We introduce a multiplex technique for the single-laser-shot determination of S
      branch Raman linewidths with high accuracy and precision by implementing hybrid
      femtosecond (fs)/picosecond (ps) rotational coherent anti-Stokes Raman
      spectroscopy (CARS) with multiple spatially and temporally separated probe beams
      derived from a single laser pulse. The probe beams scatter from the rotational
      coherence driven by the fs pump and Stokes pulses at four different probe pulse
      delay times spanning 360 ps, thereby mapping collisional coherence dephasing in
      time for the populated rotational levels. The probe beams scatter at different
      folded BOXCARS angles, yielding spatially separated CARS signals which are
      collected simultaneously on the charge coupled device camera. The technique
      yields a single-shot standard deviation (1sigma) of less than 3.5% in the
      determination of Raman linewidths and the average linewidth values obtained for
      N(2) are within 1% of those previously reported. The presented technique opens
      the possibility for correcting CARS spectra for time-varying collisional
      environments in operando.

PMID- 24322076
TI  - Surface-enhanced fluorescence of a dye-doped polymer layer with plasmonic band
      edge tuning.
AB  - We investigated experimentally the influence of 1D rectangular Au gratings on
      fluorescence. The formation of a bandgap in the dispersion relation is confirmed
      by our experiment. At the edge of this bandgap, the fluorescence of the dye can
      be strongly enhanced due to the surface plasmon polaritons' large density of
      states. By structural design we tuned the plasmonic band edges to the wavelength
      of the fluorescence of the dye molecules. An optimized Au grating structure with
      a duty ratio of 3/4 is found to achieve up to 120 times stronger fluorescence
      than that of a planar metal surface. 

PMID- 24322078
TI  - Frequency downshift of Nd:YAG lasers and terahertz radiation.
AB  - The interaction between an intense laser and a cotraveling relativistic dense
      electron beam could result in the downshifting of the laser frequency. It is
      theoretically analyzed that this process can generate a coherent terahertz
      radiation. The radiation energy could reach the order of 1 mJ per shot in the
      duration of 100 ps, or a temporal radiation power of 10 MW, with a set of
      practically relevant parameters.

PMID- 24322077
TI  - Giant electro-optic effect in nanodisordered KTN crystals.
AB  - The electro-optic (EO) effect in nanodisordered potassium tantalate niobate (KTN)
      crystal is quantitatively investigated. It is found out that the EO coefficient
      of nanodisordered KTN crystal depends not only on the cooling temperature but
      also on the cooling rate. A larger EO coefficient can be obtained by employing a
      faster cooling rate. A Kerr EO efficient (s(11) - s(12) = 6.94 * 10(-14)
      m(2)/V(2)) is obtained at a cooling rate of 0.45  degrees C/s. The enhanced EO
      efficient by employing a faster cooling rate will be greatly beneficial for a
      variety of applications such as laser Q switches, laser pulse shaping, high-speed
      optical shutters, and modulating retroreflectors.

PMID- 24322079
TI  - Absolute frequency measurement of rubidium 5S-7S two-photon transitions.
AB  - We report the absolute frequency measurements of rubidium 5S-7S two-photon
      transitions with a cw laser digitally locked to an atomic transition and
      referenced to an optical frequency comb. The narrow, two-photon transition, 5S-7S
      (760 nm), insensitive to first-order in a magnetic field, is a promising
      candidate for frequency reference. The performed tests yielded more accurate
      transition frequencies than previously reported.

PMID- 24322080
TI  - Soliton pair generation in the interactions of Airy and nonlinear accelerating
      beams.
AB  - We investigate numerically the interactions of two in-phase and out-of-phase Airy
      beams and nonlinear (NL) accelerating beams in Kerr and saturable NL media, in
      one transverse dimension. We find that bound and unbound soliton pairs, as well
      as single solitons, can form in such interactions. If the interval between two
      incident beams is large relative to the width of their first lobes, the generated
      soliton pairs just propagate individually and do not interact. However, if the
      interval is comparable to the widths of the maximum lobes, the pairs interact and
      display varied behavior. In the in-phase case, they attract each other and
      exhibit stable bound, oscillating, and unbound states, after shedding some
      radiation initially. In the out-of-phase case, they repel each other and, after
      an initial interaction, fly away as individual solitons. While the incident beams
      display acceleration, the solitons or soliton pairs generated from those beams do
      not. 

PMID- 24322081
TI  - Probing structural inhomogeneity of graphene layers via nonlinear optical
      scattering.
AB  - Incoherent optical second harmonic generation (SHG) is studied from series of
      multilayer graphene samples of various thickness manufactured by chemical vapor
      deposition technique and deposited over 150 MUm thick glass slides. Two different
      values of the correlation lengths are obtained from the linear and SHG
      indicatrices and reveal the existence of two types of optical scatterers. The
      first one is associated with homogeneous graphene areas, while the second one
      originates from wrinkles at the interdomain boundaries. Second harmonic imaging
      microscopy used to map the distribution of the second-order polarization at the
      nanoscale confirms the results of the nonlinear scattering data.

PMID- 24322082
TI  - Divided-pulse nonlinear compression.
AB  - We report on the nonlinear pulse compression of temporally divided pulses, which
      is presented in a proof-of-principle experiment. A single 320 fs pulse is divided
      into four replicas, spectrally broadened in a solid-core fiber, and subsequently
      recombined. This approach makes it possible to reduce the nonlinearities in the
      fiber and therefore to use total input peak power of about 13.3 MW, which is more
      than three times higher than the self-focusing threshold. Finally, the combined
      output pulse could be compressed to sub-100 fs pulse duration. This general and
      universal approach holds promise for overcoming fundamental limitations of the
      pulse peak power that lead to destruction of the fiber or ionization limitations
      in high-energy hollow-core compression.

PMID- 24322083
TI  - Quantitative spectroscopy on individual wire, slot, bow-tie, rectangular, and
      square-shaped optical antennas.
AB  - By using a recently introduced approach combining a focus-modulation technique
      with a common-path interferometer, we measure quantitatively the extinction,
      scattering, and absorption cross-section spectra of individual optical antennas.
      The experimental results on thin-wire antennas, slot antennas, bow-tie antennas,
      rectangular antennas, and square-shaped antennas resonating at around 1.4 MUm
      wavelength are discussed. We find increased resonant scattering cross sections
      for the latter four antennas compared to the thin-wire antenna, both in absolute
      terms and relative to the absorption cross section. The square-shaped antenna's
      resonant extinction cross section approaches the limit of a coherent point
      dipole. However, the ratio of the resonant extinction cross section to the
      geometrical cross section of 38 is largest for the simple thin-wire antenna.

PMID- 24322084
TI  - Optical manipulation of aerosol droplets using a holographic dual and single beam
      trap.
AB  - We present optical trapping and manipulation of pure water and salt water
      airborne droplets of various sizes ranging from sub-micrometers up to several
      tens of micrometers in a holographic dual and single beam trap. In the dual beam
      trap, successful fusion of droplets as well as precise delivery of many droplets
      and manipulation of multiple droplets are demonstrated. Furthermore, employing
      the transfer of the orbital angular momentum of light from Laguerre-Gaussian
      beams, we show that the water droplets orbit around the beam propagation axis and
      their tangential speed can be controlled by beam waist magnitude. We also
      demonstrate that sub-micrometer sized pure water droplets can be trapped and
      manipulated by a single beam trap with a relatively low numerical aperture. In
      this case, multiple stable trapping positions were observed, both theoretically
      and experimentally, which were due to the optical intensity oscillations in the
      focal region of the laser beam. 

PMID- 24322085
TI  - A sensitive x-ray phase contrast technique for rapid imaging using a single phase
      grid analyzer.
AB  - Phase contrast x-ray imaging (PCXI) is a promising imaging modality, capable of
      sensitively differentiating soft tissue structures at high spatial resolution.
      However, high sensitivity often comes at the cost of a long exposure time or
      multiple exposures per image, limiting the imaging speed and possibly increasing
      the radiation dose. Here, we demonstrate a PCXI method that uses a single short
      exposure to sensitively capture sample phase information, permitting high speed x
      ray movies and live animal imaging. The method illuminates a checkerboard phase
      grid to produce a fine grid-like intensity reference pattern at the detector,
      then spatially maps sample-induced distortions of this pattern to recover
      differential phase images of the sample. The use of a phase grid is an
      improvement on our previous absorption grid work in two ways. There is minimal
      loss in x-ray flux, permitting faster imaging, and, a very fine pattern is
      produced for homogenous high spatial resolution. We describe how this pattern
      permits retrieval of five images from a single exposure; the sample phase
      gradient images in the horizontal and vertical directions, a projected phase
      depth image, an edge-enhanced image, and a type of scattering image. Finally, we
      describe how the reconstruction technique can achieve subpixel distortion
      retrieval and study the behavior of the technique in regard to analysis
      technique, Talbot distance, and exposure time. 

PMID- 24322086
TI  - High-temperature fiber-optic Fabry-Perot interferometric pressure sensor
      fabricated by femtosecond laser.
AB  - In this Letter, we report on a fiber-optic Fabry-Perot interferometric pressure
      sensor with its external diaphragm surface thinned and roughened by a femtosecond
      laser. The laser-roughened surface helps to eliminate outer reflections from the
      external diaphragm surface and makes the sensor immune to variations in the
      ambient refractive index. The sensor is demonstrated to measure pressure in a
      high-temperature environment with low-temperature dependence. 

PMID- 24322087
TI  - Etching rate enhancement by shaped femtosecond pulse train electron dynamics
      control for microchannels fabrication in fused silica glass.
AB  - The dependence of the etching rate on the ultrafast pulse shaping is observed
      when microchannels are fabricated in fused silica glass using the method of
      femtosecond laser irradiation followed by chemical etching. In comparison with
      the conventional femtosecond pulses, the temporally shaped pulse trains can
      greatly enhance the etching rate under the same processing conditions. The
      enhancement is mainly attributed to the localized transient electron dynamics
      control by shaping the ultrafast pulse, resulting in higher photon absorption
      efficiency and uniform photomodification zone. Furthermore, processing
      parameters, including pulse delay and pulse energy distribution ratio, have also
      been investigated to optimize microchannels fabrication. 

PMID- 24322088
TI  - Fiber-tip high-temperature sensor based on multimode interference.
AB  - A fiber-tip high-temperature sensor based on multimode interference is
      demonstrated both theoretically and experimentally. The temperature sensor
      presented can measure a broad temperature interval ranging from room temperature
      to 1089  degrees C. An average sensitivity of 11.4 pm/ degrees C is achieved
      experimentally.

PMID- 24322089
TI  - Widely time-dispersion-tuned fiber optical oscillator and frequency comb based on
      multiple nonlinear processes.
AB  - An all-fiber optical oscillator based on three nonlinear processes, namely
      stimulated Raman scattering and broad-band and narrow-band optical parametric
      amplification, is presented and experimentally characterized. The wavelength
      tuning is achieved by means of the time-dispersion technique and spans over 160
      nm. Through the same technique a fast tunable optical frequency comb has been
      realized exploiting cascaded four-wave mixing.

PMID- 24322090
TI  - Two-tone frequency-modulation spectroscopy in off-axis cavity.
AB  - As opposed to a conventional optical resonator, an off-axis-aligned cavity is
      able to transmit without distortion radiation modulated at a frequency even far
      above the cavity bandpass. This allows us to implement a simple spectroscopic
      technique that combines the cavity path-length enhancement of integrated cavity
      output spectroscopy (ICOS) and the noise reduction associated with radio
      frequency modulation (FM). An FM-ICOS spectrometer is demonstrated for the first
      time using a two-tone modulation technique. The performance is compared to the
      traditional ICOS by examining the acetylene absorption at 1543.77 nm. A signal-to
      noise ratio improvement by a factor 3.5 is found with our proof-of-concept setup.
      Larger improvements are expected in a more optimized setup.

PMID- 24322091
TI  - Strong magnetochiral dichroism of helical structures of garnet particles.
AB  - We report on the occurrence of strong nonreciprocal magnetochiral dichroism in
      helical structures of magnetic garnet spheres, which emerges as a result of the
      simultaneous lack of time-reversal and space-inversion symmetries, by means of
      rigorous full-electrodynamic calculations using the layer-multiple-scattering
      method. It is shown that a strong effect appears in flat band regions associated
      with enhanced natural and magnetic optical activity. 

PMID- 24322092
TI  - Mechanism of optical terahertz-transmission modulation in an organic/inorganic
      semiconductor interface and its application to active metamaterials.
AB  - Terahertz (THz) transmission modulation through copper phthalocyanine (CuPc)
      coated Si under various laser light irradiation conditions was investigated using
      THz time-domain spectroscopy. The charge carrier transfer from Si to CuPc is
      crucial for photo-induced metallization, and the thickness of the CuPc layer is a
      critical parameter for achieving high charge carrier density for metallization.
      Transmission through a split-ring resonator array metamaterial, fabricated on
      CuPc-coated Si, can be efficiently modulated by laser light irradiation. Our
      findings may open the way for various types of metamaterials using organic
      conjugated materials that are suitable for easy device fabrication using printing
      technologies. 

PMID- 24322093
TI  - Image storage in coumarin-based copolymer thin films by photoinduced
      dimerization.
AB  - We report a technique to encode grayscale digital images in thin films composed
      of copolymers containing coumarins. A nonlinear microscopy setup was implemented
      and two nonlinear optical processes were used to store and read information. A
      third-order process (two-photon absorption) was used to photoinduce a controlled
      dimer-to-monomer ratio within a defined tiny volume in the material, which
      corresponds to each recorded bit of data. Moreover, a second-order process
      (second-harmonic generation) was used to read the stored information, which has
      been found to be highly dependent upon the monomer-to-dimer ratio. 

PMID- 24322094
TI  - Concept for three-dimensional optical addressing by ultralow one-photon
      absorption method.
AB  - With respect to experimental condition, we have investigated the point spread
      function of a high numerical aperture objective lens, taking into account the
      absorption effect of the studied material. By using a material possessing an
      ultralow one-photon absorption (LOPA) coefficient at the excitation wavelength,
      the light beam can penetrate deeply inside the material and be tightly focused
      into a subwavelength spot, almost the same as in the absence of material.
      Combining tight focusing and ultralow absorption conditions, we show that LOPA
      based microscopy is thus capable of three-dimensional imaging and fabrication
      with long penetration depth up to 300 MUm. As compared to the commonly used two
      photon absorption microscope, the LOPA method allows simplification of the
      experimental setup and also minimization of the photodamaging or bleaching effect
      of materials.

PMID- 24322095
TI  - Disordered microstructure polymer optical fiber for stabilized coherent random
      fiber laser.
AB  - We have demonstrated the realization of a random polymer fiber laser (RPFL) based
      on laser dye Pyrromethene 597-doped one-dimensional disordered polymer optical
      fiber (POF). The stabilized coherent laser action for the disordered POF has been
      obtained by the weak optical multiple scattering of the polyhedral oligomeric
      silsesquioxanes nanoparticles in the core of the POF in situ formed during
      polymerization, which was enhanced by the waveguide confinement effect.
      Meanwhile, the threshold of our RPFL system is almost one order of magnitude
      lower than that of the liquid core random fiber laser reported previously, which
      promotes the development of random lasers. 

PMID- 24322096
TI  - Generating a three-dimensional dark focus from a single conically refracted light
      beam.
AB  - We report here the generation of a three-dimensional (3D) dark focus from a
      single focused monochromatic Gaussian beam that undergoes conical refraction when
      it propagates along one of the optic axes of a biaxial crystal. We study the
      resulting ring intensity pattern behind the crystal as a function of the ratio
      between the ring radius and the beam waist and derive the particular parameter
      values for which a 3D dark focus with null intensity at the ring center is
      formed. We have performed experiments with a KGd(WO(4))(2) biaxial crystal,
      reporting the generation of a bottle beam in full agreement with our theoretical
      investigations.

PMID- 24322097
TI  - Biphoton manipulation with a fiber-based pulse shaper.
AB  - We demonstrate spectral shaping of entangled photons in the telecom band with a
      programmable, fiber-based optical filter. The fine-resolution spectral control
      permits implementation of length-40 Hadamard codes, through which we are able to
      verify frequency anticorrelation with a 20-fold increase in total counts over
      that permitted by the equivalent pair of monochromators at the same input flux.
      By programming the complex spectral transmission function corresponding to a Mach
      Zehnder interferometer, we also construct variations on Franson interferometers
      that are free from mechanical instabilities, demonstrating spectral phase
      independence in the slow-detector limit, in which all temporal features are
      unobservable. Our configuration furnishes a single, compact arrangement for
      manipulating telecom biphotons and characterizing their quality. 

PMID- 24322098
TI  - Hybrid single quantum well InP/Si nanobeam lasers for silicon photonics.
AB  - We report on a hybrid InP/Si photonic crystal nanobeam laser emitting at 1578 nm
      with a low threshold power of ~14.7 MUW. Laser gain is provided from a single
      InAsP quantum well embedded in a 155 nm InP layer bonded on a standard silicon-on
      insulator wafer. This miniaturized nanolaser, with an extremely small modal
      volume of 0.375(lambda/n)(3), is a promising and efficient light source for
      silicon photonics.

PMID- 24322099
TI  - Measurement method of the relative propagation delay of two signals based on
      modified caliper ruler.
AB  - A novel measurement technique for the relative propagation delay of two signals
      based on a caliper ruler is proposed. The technique is applied to the chromatic
      dispersion measurements of single-mode fiber (SMF), dispersion-compensation
      fiber, and dispersion-shifted fiber. Compared to the conventional time-of-flight
      method, dispersion can be measured even when the delay difference is smaller than
      the measurement pulse's width. The sign of dispersion is preserved during
      measurement. The scheme also supports the usage of multiple wavelengths
      simultaneously for fast measurement. Measurement error of less than 0.2 ps/(km *
      nm) in SMF is experimentally demonstrated.

PMID- 24322100
TI  - Liquid crystal spatial light modulator with very large phase modulation operating
      in high harmonic orders.
AB  - Unusually large phase modulation in a commercial liquid crystal spatial light
      modulator (LCSLM) is reported. Such a situation is obtained by illuminating with
      visible light a device designed to operate in the infrared range. The phase
      modulation range reaches 6pi radians in the red region of the visible spectrum
      and 10pi radians in the blue region. Excellent diffraction efficiency in high
      harmonic orders is demonstrated despite a concomitant and non-negligible Fabry
      Perot interference effect. This type of SLM opens the possibility to implement
      diffractive elements with reduced chromatic dispersion or chromatic control. 

PMID- 24322101
TI  - Resonant excited state absorption and relaxation mechanisms in Tb3+-doped calcium
      aluminosilicate glasses: an investigation by thermal mirror spectroscopy.
AB  - Resonant excited state absorption (ESA) and relaxation processes in Tb(3+)-doped
      aluminosilicate glasses are quantitatively evaluated. A model describing the
      excitation steps and upconversion emission is developed and applied to interpret
      the results from laser-induced surface deformation using thermal mirror
      spectroscopy. The fluorescence quantum efficiency of level (5)D(4) was found to
      be close to unity and concentration independent while, for the level (5)D(3), it
      decreases with Tb(3+) concentration. Emission spectroscopy measurements supported
      these results. ESA cross sections are found to be more than three orders of
      magnitude higher than the ground state absorption cross section.

PMID- 24322102
TI  - Ultra-wideband three-dimensional optoacoustic tomography.
AB  - Broadband optoacoustic waves generated by biological tissues excited with
      nanosecond laser pulses carry information corresponding to a wide range of
      geometrical scales. Typically, the frequency content present in the signals
      generated during optoacoustic imaging is much larger compared to the frequency
      band captured by common ultrasonic detectors, the latter typically acting as
      bandpass filters. To image optical absorption within structures ranging from
      entire organs to microvasculature in three dimensions, we implemented
      optoacoustic tomography with two ultrasound linear arrays featuring a center
      frequency of 6 and 24 MHz, respectively. In the present work, we show that
      complementary information on anatomical features could be retrieved and provide a
      better understanding on the localization of structures in the general anatomy by
      analyzing multi-bandwidth datasets acquired on a freshly excised kidney.

PMID- 24322103
TI  - Superballistic growth of the variance of optical wave packets.
AB  - We experimentally demonstrate that hybrid ordered-disordered photonic lattices
      can generate faster than the ballistic growth of the second moment of a spreading
      wave packet for parametrically large time intervals. 

PMID- 24322104
TI  - Broadband infrared supercontinuum generation in hexagonal-lattice tellurite
      photonic crystal fiber with dispersion optimized for pumping near 1560 nm.
AB  - We report on supercontinuum generation (SG) in a hexagonal lattice tellurite
      photonic crystal fiber (PCF). The fiber has a regular lattice with a lattice
      constant Lambda = 2 MUm, linear filling factor d/Lambda = 0.75, and a solid core
      2.7 MUm in diameter. Dispersion, calculated from scanning electron microscope
      (SEM) image of drawn fiber, has zero dispersion wavelength (ZDW) at 1410 and 4236
      nm with a maximum of 193 ps/nm/km at 2800 nm. Under pumping with 150 fs/36
      nJ/1580 nm pulses, supercontinuum spectrum in a bandwidth from 800 nm to over
      2500 nm was observed in a 2 cm long PCF sample, which is comparable to results
      reported for suspended core tellurite PCFs pumped at wavelengths over 1800 nm.
      Measured spectrum is analyzed numerically with good agreement, and observed
      spectral broadening is interpreted. To our best knowledge, tellurite glass,
      regular lattice PCFs for successful SG in this bandwidth have not been reported
      before.

PMID- 24322105
TI  - Mid-infrared supercontinuum generation in fluoroindate fiber.
AB  - We report the generation of mid-infrared supercontinua in a step-index
      fluoroindate-based fiber. The large core of the fluoroindate fiber allows the
      guiding of multiwatt laser power over a broad spectral range. These fibers
      exhibit zero dispersion at 1.83 MUm, minimal loss of 0.1 dB/m at 3.2 MUm up to
      only 0.8 dB/m at 5 MUm. These specifications enable mid-infrared supercontinuum
      generation and propagation with low loss. By using mid-infrared ultrashort laser
      pulses from an optical parametric amplifier, we demonstrate generation of a 20 dB
      spectral flatness supercontinua from 2.7 to 4.7 MUm in the fluoroindate fiber,
      which is twice the spectral broadening compared to a ZBLAN fiber under similar
      conditions.

PMID- 24322106
TI  - High-peak-power, high-energy, high-average-power pulsed fiber laser system with
      versatile pulse duration and shape.
AB  - We present a pulsed fiber laser system with average power up to 265 W, pulse
      energy up to 10.6 mJ, pulse duration adjustable in the range 500 ps-500 ns,
      repetition rate fully controllable from single-shot operation up to 1 MHz, and
      the ability to control peak power independently of pulse energy. The system has a
      compact, all-spliced construction. Such a versatile laser will have wide
      applications in materials processing.

PMID- 24322107
TI  - Monitoring DNA hybridization using optical microcavities.
AB  - The development of DNA analysis methods is rapidly expanding as interest in
      characterizing subtle variations increases in biomedicine. A promising approach
      is based on evanescent field sensors that monitor the hybridization process in
      real time. However, one challenge is discriminating between nonspecific and
      specific attachment. Here, we demonstrate a hybridization sensor based on an
      integrated toroidal optical microcavity. The surface is functionalized with ssDNA
      using an epoxide method, and the evanescent wave of the microresonator excites a
      fluorescent label on the complementary ssDNA during hybridization. Based on a
      temporal analysis, the different binding regimes can be identified. 

PMID- 24322108
TI  - Spectrally multiplexed chromatic confocal multipoint sensing.
AB  - We present a concept for chromatic confocal distance sensing that employs two
      levels of spectral multiplexing for the parallelized evaluation of multiple
      lateral measurement points; at the first level, the chromatic confocal principle
      is used to encode distance information within the spectral distribution of the
      sensor signal. For lateral multiplexing, the total spectral bandwidth of the
      sensor is split into bands. Each band is assigned to a different lateral
      measurement point by a segmented diffractive element. Based on this concept, we
      experimentally demonstrate a chromatic confocal three-point sensor that is
      suitable for harsh production environments, since it works with a single-point
      spectrometer and does not require scanning functionality. The experimental system
      has a working distance of more than 50 mm, a measurement range of 9 mm, and an
      axial resolution of 50 MUm.

PMID- 24322109
TI  - Photocurrent limit in nanowires.
AB  - Square root photocurrent dependences of nanowires on light intensity were
      reported in the literature without clarification of the limiting effect. In this
      Letter, we derived a relation excellently fitting the observed nonlinearities
      and, intensifying the significance of the result, we demonstrated that the fit
      parameters involved can be employed to determine the impurity concentration and
      electronic response time of nano-sized semiconductors. 

PMID- 24322110
TI  - Experimental demonstration of localized Brillouin gratings with low off-peak
      reflectivity established by perfect Golomb codes.
AB  - Dynamic Brillouin gratings (DBGs), inscribed by comodulating two writing pump
      waves with a perfect Golomb code, are demonstrated and characterized
      experimentally. Compared with pseudo-random bit sequence (PRBS) modulation of the
      pump waves, the Golomb code provides lower off-peak reflectivity due to the
      unique properties of its cyclic autocorrelation function. Golomb-coded DBGs allow
      the long variable delay of one-time probe waveforms with higher signal-to-noise
      ratios, and without averaging. As an example, the variable delay of return-to
      zero, on-off keyed data at a 1 Gbit/s rate, by as much as 10 ns, is demonstrated
      successfully. The eye diagram of the reflected waveform remains open, whereas
      PRBS modulation of the pump waves results in a closed eye. The variable delay of
      data at 2.5 Gbit/s is reported as well, with a marginally open eye diagram. The
      experimental results are in good agreement with simulations.

PMID- 24322111
TI  - Characterization of 700 MUJ T rays generated during high-power laser solid
      interaction.
AB  - Laser-produced solid density plasmas are well-known as table-top sources of
      electromagnetic radiation. Recent studies have shown that energetic broadband
      terahertz pulses (T rays) can also be generated from laser-driven compact ion
      accelerators. Here we report the measurement of record-breaking T-Ray pulses with
      energies no less than 0.7 mJ. The terahertz spectrum has been characterized for
      frequencies ranging from 0.1-133 THz. The dependence of T-Ray yield on incident
      laser energy is linear and shows no tendencies of saturation. The noncollinear
      emission pattern and the high yield reveal that the T rays are generated by the
      transient field at the rear surface of the solid target.

PMID- 24322112
TI  - Time-to-space conversion of ultrafast waveforms at 1.55 MUm in a planar
      periodically poled lithium niobate waveguide.
AB  - We report the first demonstration, to our knowledge, of time-to-space conversion
      of subpicosecond pulses in a slab nonlinear waveguide. By vertically confining
      the nondegenerate sum-frequency generation interaction between a spatially
      dispersed 100 fs signal pulse at 1.55 MUm and a reference pulse in a titanium
      indiffused planar periodically poled lithium niobate crystal waveguide, we have
      attained a conversion efficiency of 0.1% and a conversion efficiency slope of 4%
      per watt of reference beam power. This was achieved while maintaining high
      conversion resolution, with a measured time window of operation of 48 ps
      resulting in a serial-to-parallel demultiplexing factor of 90.

PMID- 24322113
TI  - Optical-wireless-optical full link for polarization multiplexing quadrature
      amplitude/phase modulation signal transmission.
AB  - We propose and experimentally demonstrate an optical wireless integration system
      at the Q-band, in which up to 40 Gb/s polarization multiplexing multilevel
      quadrature amplitude/phase modulation (PM-QAM) signal can be first transmitted
      over 20 km single-mode fiber-28 (SMF-28), then delivered over a 2 m 2 * 2
      multiple-input multiple-output wireless link, and finally transmitted over
      another 20 km SMF-28. The PM-QAM modulated wireless millimeter-wave (mm-wave)
      signal at 40 GHz is generated based on the remote heterodyning technique, and
      demodulated by the radio-frequency transparent photonic technique based on
      homodyne coherent detection and baseband digital signal processing. The classic
      constant modulus algorithm equalization is used at the receiver to realize
      polarization demultiplexing of the PM-QAM signal. For the first time, to the best
      of our knowledge, we realize the conversion of the PM-QAM modulated wireless mm
      wave signal to the optical signal as well as 20 km fiber transmission of the
      converted optical signal.

PMID- 24322114
TI  - 39.1 MUJ picosecond ultraviolet pulses at 355 nm with 1 MHz repeat rate.
AB  - Based on our reliable high-power picosecond laser source with high beam
      qualities, we designed a compact and efficient third harmonic generation scheme
      by cascading a frequency doubling and a sum frequency generation using LBO as the
      nonlinear material. A maximum output of 39.1 W with a repeat rate of 1 MHz at 355
      nm was obtained, which implied a pulse energy of 39.1 MUJ, which was the highest
      picosecond UV pulse energy with an all-solid-state setup so far. The total
      conversion efficiency from infrared to UV was up to 46%. And the output UV has
      excellent beam qualities with an M-square factor less than 1.1.

PMID- 24322115
TI  - Single channel in-line multimodal digital holography.
AB  - We present a new single channel in-line setup for holographic recording that can
      properly record various objects that cannot be recorded by the Gabor holographic
      method. This configuration allows the recording of holograms based on several
      modalities while addressing important issues of the original Gabor setup,
      including the well-known twin-image problem and the weak scattering condition. 

PMID- 24322116
TI  - Structured illumination fluorescence microscopy with distorted excitations using
      a filtered blind-SIM algorithm.
AB  - Structured illumination microscopy (SIM) is a powerful technique for obtaining
      super-resolved fluorescence maps of samples, but it is very sensitive to
      aberrations or misalignments affecting the excitation patterns. Here, we present
      a reconstruction algorithm that is able to process SIM data even if the
      illuminations are strongly distorted. The approach is an extension of the recent
      blind-SIM technique, which reconstructs simultaneously the sample and the
      excitation patterns without a priori information on the latter. Our algorithm was
      checked on synthetic and experimental data using distorted and nondistorted
      illuminations. The reconstructions were similar to that obtained by up-to-date
      SIM methods when the illuminations were periodic and remained artifact-free when
      the illuminations were strongly distorted. 

PMID- 24322117
TI  - Cylindrical quasi-Gaussian beams.
AB  - Making use of the complex-source-point method in cylindrical coordinates, an
      exact solution representing a cylindrical quasi-Gaussian beam of arbitrary waist
      w(0) satisfying both the Helmholtz and Maxwell's equations is introduced. The
      Cartesian components of the electromagnetic field are derived stemming from
      different polarizations of the magnetic and electric vector potentials based on
      Maxwell's vectorial equations and Lorenz's gauge condition, without any
      approximations. Computations illustrate the theory for tightly focused and quasi
      collimated cylindrical beams. The results are particularly useful in beam-forming
      design using high-aperture or collimated cylindrical laser beams in imaging
      microscopy, particle manipulation, optical tweezers, and the study of scattering,
      radiation forces, and torque on cylindrical structures.

PMID- 24322118
TI  - Focusing and imaging of a virtual all-optical tunable terahertz Fresnel zone
      plate.
AB  - A virtual all-optical tunable terahertz Fresnel zone plate is achieved utilizing
      the localized distribution of the transient electron plasma on a silicon wafer.
      Its focusing and imaging performance are experimentally demonstrated.
      Experimental results show that the effect of the virtual zone plate is the same
      as an actual one. Adjusting the spatial pattern of the electron plasma, the
      central wavelength and the focal length of the virtual zone plate can be all
      optically dynamically steered. The research is a significant step to the
      development of tunable optical imaging elements. 

PMID- 24322119
TI  - High speed, high fidelity detection of an atomic hyperfine qubit.
AB  - Fast and efficient detection of the qubit state in trapped ion systems is
      critical for implementing quantum error correction and performing fundamental
      tests such as a loophole-free Bell test. In this work we present a simple qubit
      state detection protocol for a (171)Yb+ hyperfine atomic qubit trapped in a
      microfabricated surface trap, enabled by high collection efficiency of the
      scattered photons and low background photon count rate. We demonstrate average
      detection times of 10.5, 28.1, and 99.8 MUs, corresponding to state detection
      fidelities of 99%, 99.856(8)%, and 99.915(7)%, respectively.

PMID- 24322120
TI  - All-fiber, ultra-wideband tunable laser at 2 MUm.
AB  - We report a direct diode-pumped all-fiber tunable laser source at 2 MUm with a
      tuning range of more than 250 nm. A 3 dB power flatness of 200 nm with a maximum
      output power of 30 mW at 1930 nm was achieved. The laser has a high optical
      signal-to-noise ratio (OSNR) of more than 40 dB across the whole tuning range.

PMID- 24322121
TI  - Nondecaying surface plasmon polaritons in linear chains of silver nanospheroids.
AB  - We consider propagation of surface plasmon polaritons in linear chains of
      equidistant metallic nanospheroids. We show that, for suitably chosen parameters,
      the propagation is free of spatial decay in spite of the full account of
      absorptive losses in the metal. 

PMID- 24322122
TI  - Effect of correction of aberration dynamics on chaos in human ocular
      accommodation.
AB  - We used adaptive optics to determine the effect of monochromatic aberration
      dynamics on the level of chaos in the accommodation control system. Four
      participants viewed a stationary target while the dynamics of their aberrations
      were either left uncorrected, defocus was corrected, or all aberrations except
      defocus were corrected. Chaos theory analysis was used to discern changes in the
      accommodative microfluctuations. We found a statistically significant reduction
      in the chaotic nature of the accommodation microfluctuations during correction of
      defocus, but not when all aberrations except defocus were corrected. The Lyapunov
      exponent decreased from 0.71 +/- 0.07 D/s (baseline) to 0.55 +/- 0.03 D/s
      (correction of defocus fluctuations). As the reduction of chaos in physiological
      signals is indicative of stress to the system, the results indicate that for the
      participants included in this study, fluctuations in defocus have a more profound
      effect than those of the other aberrations. There were no changes in the power
      spectrum between experimental conditions. Hence chaos theory analysis is a more
      subtle marker of changes in the accommodation control system and will be of value
      in the study of myopia onset and progression.

PMID- 24322123
TI  - Angular-domain scattering interferometry.
AB  - We present an angular-scattering optical method that is capable of measuring the
      mean size of scatterers in static ensembles within a field of view less than 20
      MUm in diameter. Using interferometry, the method overcomes the inability of
      intensity-based models to tolerate the large speckle grains associated with such
      small illumination areas. By first estimating each scatterer's location, the
      method can model between-scatterer interference as well as traditional single
      particle Mie scattering. Direct angular-domain measurements provide finer angular
      resolution than digitally transformed image-plane recordings. This increases
      sensitivity to size-dependent scattering features, enabling more robust size
      estimates. The sensitivity of these angular-scattering measurements to various
      sizes of polystyrene beads is demonstrated. Interferometry also allows recovery
      of the full complex scattered field, including a size-dependent phase profile in
      the angular-scattering pattern.

PMID- 24322124
TI  - Dispersion of the resonant nonlinear optical susceptibility obtained with
      femtosecond time-domain coherent anti-Stokes Raman scattering.
AB  - We propose and experimentally demonstrate a method that is capable of resolving
      both real and imaginary parts of third-order nonlinearity (chi(3)) in the
      vicinity of Raman resonances. Dispersion of chi(3) can be obtained from a medium
      probed within microscopic volumes with a spectral resolution of better than 0.10
      cm(-1).

PMID- 24322125
TI  - Coupling of multiple LSP and SPP resonances: interactions between an elongated
      nanoparticle and a thin metallic film.
AB  - We study the coupling interactions between a progressively elongated silver
      nanoparticle and a silver film on a glass substrate. Specifically, we investigate
      how the coupling between localized surface plasmons (LSPs) and propagating
      surface plasmon polaritons (SPPs) is influenced by nanoparticle length. Although
      the multiple resonances supported by the nanoparticle are effectively standing
      wave surface plasmons, their interaction with the SPP continuum of the underlying
      Ag film indicates that their spectral response is still localized in nature. It
      is found that these LSP-SPP interactions are not limited to small particles, but
      that they are present as well for extremely long particles, with a transition to
      the SPP coupling interactions of a bilayer metallic film system beginning at a
      particle length of approximately 5 MUm.

PMID- 24322126
TI  - Preparing arbitrary pure states of spatial qudits with a single phase-only
      spatial light modulator.
AB  - Spatial qudits are D-dimensional (D >= 2) quantum systems carrying information
      encoded in the discretized transverse momentum and position of single photons. We
      present a proof-of-principle demonstration of a method for preparing arbitrary
      pure states of such systems by using a single phase-only spatial light modulator
      (SLM). The method relies on the encoding of the complex transmission function
      corresponding to a given spatial qudit state onto a preset diffraction order of a
      phase-only grating function addressed at the SLM. Fidelities of preparation above
      94% were obtained with this method, which is simpler, less costly, and more
      efficient than those that require two SLMs for the same purpose.

PMID- 24322127
TI  - Thermal behavior of resonant waveguide-grating mirrors in Yb:YAG thin-disk
      lasers.
AB  - We present the experimental investigations of different designs of resonant
      waveguide-grating (RWG) mirrors, used as intracavity folding mirrors in an Yb:YAG
      thin-disk laser (TDL). The investigation was focused on the rise of the surface
      temperature due to the coupling of the incident radiation to a waveguide mode as
      well as on laser efficiency, polarization, and wavelength selectivity. It was
      found that the damage threshold and efficiency can be increased significantly
      with a proper design of the structure in comparison to the simplest design with a
      single waveguide layer. So far, the presented RWG allow the generation of linear
      polarization with a narrow spectral linewidth down to 25 pm FWHM in a fundamental
      mode Yb:YAG TDL. Damage thresholds of 60 kW/cm(2) have been reached where only 63
      K of surface temperature increase was observed. This showed that the improved
      mirrors are suitable for the generation of kW-class narrow linewidth, linearly
      polarized Yb:YAG TDL.

PMID- 24322128
TI  - Plasmonic petal-shaped beam for microscopic phase-sensitive SPR biosensor with
      ultrahigh sensitivity.
AB  - Differential phase measurement between radially polarized (RP) and azimuthally
      polarized (AP) beams is an important technique in microscopic surface plasmon
      resonance (SPR) biosensors as reported in our earlier works [Opt. Lett.37, 2091
      (2012); Appl. Phys. Lett.102, 011114 (2013)]. However, such a technique suffers
      complex beam splitting, detection, and data processing procedures for RP and AP
      beams which may lower the accuracy of phase measurement. In this Letter, a novel
      plasmonic petal-shaped vector beam is proposed instead of RP and AP beams,
      greatly simplifying the sensor system and enabling single measurement in
      differential interferometry. Moreover, an improved ultrahigh sensitivity on the
      order of 10(-7) refractive index units (RIUs) is experimentally verified in the
      proposed system.

PMID- 24322129
TI  - Low cross-talk 2 * 2 silicon electro-optic switch matrix with a double-gate
      configuration.
AB  - In this study, a low cross-talk 2 * 2 silicon electro-optic switch matrix based
      on a double-gate configuration is proposed and experimentally demonstrated. The
      switch matrix consists of four Mach-Zehnder-based 2 * 2 switching elements with
      400 MUm long modulation arms. Low cross-talk values of -31 and -43 dB are,
      respectively, obtained for the "cross" and "bar" states over a 40 nm wide
      wavelength range around 1550 nm. The values for the total steady-state power
      consumption of the "cross" and "bar" states are 40.8 and 19.1 mW, respectively.

PMID- 24322130
TI  - Spatially resolved Stokes parameters of small-area vertical-cavity surface
      emitting lasers: experiment and simulation.
AB  - We present experimental investigations on spatially resolved Stokes parameters of
      vertical-cavity surface-emitting lasers (VCSELs) with a small aperture diameter
      of 3 MUm and a monolithically integrated surface grating on top of the structure
      to technologically control the polarization. As expected, the grating fixes the
      state of polarization, but still shows both a spatially nonuniform linear
      polarization distribution of the fundamental transverse mode as well as an
      interesting eight-lobe pattern of circular polarization in terms of change of
      sign. These experimental findings are reproduced by numerical simulations using a
      fully vectorial three-dimensional model.

PMID- 24322131
TI  - Multiple-frequency measurement based on serial photonic channelization using
      optical wavelength scanning.
AB  - A serial photonic channelized radio frequency (RF) measurement scheme is proposed
      and experimentally demonstrated. This scheme can be used for instantaneous
      multiple-frequency measurement and capturing key parameters of linear frequency
      modulation signals. Based on high-speed wavelength scanning, this photonic RF
      channelizer works serially in time domain, and each wavelength labels a certain
      RF channel. With only one low-bandwidth photodetector (PD), we can implement
      multiple channel RF frequency measurements, which have a much simpler structure
      compared with parallel channelized schemes using broadband filter-bank and
      multiple PDs. 

PMID- 24322132
TI  - Far-field polarization characterization of the fundamental modes of a strip
      silicon waveguide.
AB  - The fundamental quasi-TE and quasi-TM modes of a sub-wavelength strip silicon
      waveguide are not purely TE or TM as the plane waves in free space. We
      investigate theoretically and experimentally the far-field polarization
      compositions of the two waveguide modes after they emanate from the waveguide
      facet. The measured polarization extinction ratios (PERs) of 31 dB for the quasi
      TM mode and 26 dB for quasi-TE mode using free-space polarizers are consistent
      with our numerical analysis. Moreover, our far-field simulations show that the
      free-space measurement of PERs is influenced, and in many cases limited, by the
      sizes of various apertures in the experimental setup. This suggests a potential
      trade-off between achievable PERs and overall power detection/collection
      efficiency.

PMID- 24322133
TI  - Compact wavelength-selective optical switch based on digital optical phase
      conjugation.
AB  - In this Letter, we show that digital optical phase conjugation might be utilized
      to construct a new kind of wavelength-selective switches. When incorporated with
      a multimode interferometer, these switches have wide bandwidth, high tolerance
      for fabrication error, and low polarization dependency. They might help to build
      large-scale multiwavelength nonblocking switching systems, or even to fabricate
      an optical cross-connecting or routing system on a chip. 

PMID- 24322134
TI  - Highly efficient and compact cavity oscillator for high-power, optically pumped
      gas terahertz laser.
AB  - We demonstrate a highly efficient and compact terahertz cavity oscillator that is
      based on z-cut crystal quartz used as the dichroic beam splitter, for the first
      time to the best of our knowledge. With D(2)O gas as the active medium, pumped
      with a multitransverse mode TEACO(2) laser, experimental verification was also
      presented to demonstrate the advantages of this cavity oscillator. With the
      cavity length of 120 cm, 7.4 mJ pulse energy at pulse repetition frequency of 6
      Hz, pulse width of 90 ns, and peak power of 82.2 kW were achieved at a wavelength
      of 385 MUm. Photon conversion efficiency (PCE) of 44% was obtained at the maximum
      output level from this terahertz cavity oscillator. Furthermore, to our
      knowledge, this PCE is the highest efficiency ever reported in D(2)O gas, 385 MUm
      terahertz cavity laser systems. The beam quality or M(2) factor was found to be
      about 1.77.

PMID- 24322135
TI  - Gain-switched multicarrier transmitter in a long-reach UDWDM PON with a digital
      coherent receiver.
AB  - The authors report on the downlink performance of a 10 Gb/s long-reach and ultra
      dense wavelength-division multiplexed passive optical network, based on a
      multicarrier transmitter realized by using an externally injected gain-switched
      distributed-feedback laser diode. Each of the comb channels, spaced by 10 GHz, is
      modulated with a 3 Gbaud dual polarization quadrature phase shift keying signal
      that included a 20% overhead for forward error correction. Frequency selectivity
      and enhanced receiver sensitivity is achieved by employing a digital coherent
      receiver to receive the signal. Experimental results achieved in a back-to-back
      and 100 km transmission scenarios show an excellent worst case receiver
      sensitivity of -44 dBm.

PMID- 24322136
TI  - Wavefront sensorless modal deformable mirror correction in adaptive optics:
      optical coherence tomography.
AB  - We present a method for optimization of optical coherence tomography images using
      wavefront sensorless adaptive optics. The method consists of systematic
      adjustment of the coefficients of a subset of the orthogonal Zernike bases and
      application of the resulting shapes to a deformable mirror, while optimizing
      using image sharpness as a merit function. We demonstrate that this technique can
      compensate for aberrations induced by trial lenses. Measurements of the point
      spread function before and after compensation demonstrate near diffraction limit
      imaging. 

PMID- 24322137
TI  - 320 Gb/s all-optical clock recovery and time de-multiplexing after transmission
      enabled by single quantum dash mode-locked laser.
AB  - We report, to the best of our knowledge, the first demonstration of 320 Gb/s all
      optical clock recovery and all-optical time de-multiplexing after 51 km
      transmission by exploiting single-quantum dash mode-locked laser diode (QD-MLLD).
      Based on injection locking of the QD-MLLD, the 40 GHz synchronized optical clock
      pulses were recovered from the 320 Gb/s with a pulse width of 1.9 ps and timing
      jitter of 135 fs, which allowed directly time de-multiplexing of 320-40 Gb/s
      without additional complex optoelectronic circuitry. The 320-40 Gb/s all-optical
      de-multiplexing was achieved with averaging a power penalty of 4.5 dB at BER of
      1E-6.

PMID- 24322138
TI  - Vectorial van Cittert-Zernike theorem based on spatial averaging: experimental
      demonstrations.
AB  - The van Cittert-Zernike theorem is extended to the vectorial regime based on
      spatial averaging over the observation plane, and experimental demonstrations are
      presented. The theorem connects complex vectorial source structure to the degree
      of coherence and polarization of the spatially fluctuating vectorial field in the
      far field. Experimentation is carried out by making use of the space averages as
      a replacement of ensemble averages for the Gaussian stochastic field. For
      quantitative comparison with the theorem, analytical and experimental results are
      presented for a rectangular aperture with different vectorial source structures. 

PMID- 24322139
TI  - Phase retrieval from one partial derivative.
AB  - Phase objects can be characterized using well-known methods such as shear
      interferometry and deflectometry, which provide information on the partial
      derivatives of the phase. It is often believed that for phase retrieval it is
      strictly necessary to have knowledge of two partial derivatives in orthogonal
      directions. In the praxis, this implies that the measurements have to be
      performed along two dimensions, which often requires a rotation of the object or
      rotation of the shear direction. This is time consuming and errors can be easily
      generated from the process of rotation, especially for image registration in the
      axial direction. In the present Letter, we will demonstrate that only one partial
      derivative often suffices to recover the phase, and we will discuss under which
      conditions that is possible. Simulations and validation experiments are
      presented. 

PMID- 24322140
TI  - Control of the optical field coherence by spatiotemporal light modulation.
AB  - The novel spatiotemporal optical coherence manipulation technique, which allows
      one to tailor the second-order coherence properties of a light beam, is
      introduced. With the use of an interferometric setup we show that the basic
      measure of the contrast of interference fringes, i.e., Michelson's visibility,
      can be controlled across the interference pattern by modulating the phase of the
      spectral degree of coherence. 

PMID- 24322141
TI  - Experimental generation of nonuniformly correlated partially coherent light
      beams.
AB  - We report the experimental realization of nonuniformly correlated partially
      coherent light (NUCPCL) beams by passing laser beams through a phase-only spatial
      light modulator. The characteristics of NUCPCL beams whose coherence is of
      Gaussian distribution as well as inverse Gaussian distribution are studied
      theoretically and experimentally. It is shown that the experimental observations
      are in agreement with our theoretical analysis. NUCPCL beams may have some
      applications in optical manipulation. 

PMID- 24322142
TI  - Arrayed narrow linewidth erbium-doped waveguide-distributed feedback lasers on an
      ultra-low-loss silicon-nitride platform.
AB  - We demonstrate an array of erbium-doped waveguide-distributed feedback lasers on
      an ultra-low-loss Si(3)N(4) platform. Sidewall gratings providing the lasing
      feedback are defined in the silicon-nitride layer using 248 nm stepper
      lithography, while the gain is provided by a reactive co-sputtered erbium-doped
      aluminum-oxide layer. We observe lasing output over a 12 nm wavelength range
      (1531-1543 nm) from the array of five separate lasers. Output powers of 8 MUW and
      lasing linewidths of 501 kHz are obtained. Single-mode operation is confirmed,
      with side-mode suppression ratios over 35 dB for all designs.

PMID- 24322143
TI  - Calibration of a snapshot phase-resolved polarization-sensitive spectral
      reflectometer.
AB  - This Letter describes a universal calibration theory by which conventional
      interferometry can be extended to vibration robust snapshot polarization
      sensitive spectral reflectometry without any complicated optical components or
      active devices. Experiments for verifying the proposed calibration theory have
      been conducted by using a Michelson-interferometer-based normal incidence
      spectroellipsometric system, and also some key system design considerations for
      object 3D pose tolerant measurement capability have been drawn. The proposed
      solution enables us to extract the spectroscopic ellipsometric parameter Delta(k)
      of an anisotropic object within 10 ms with high accuracy.

PMID- 24322144
TI  - Generating squeezed vacuum field with nonzero orbital angular momentum with
      atomic ensembles.
AB  - We demonstrated that by using a pump field with nonzero orbital angular momentum
      (OAM) in the polarization self-rotation squeezing process it is possible to
      generate a squeezed vacuum optical field with the matching OAM. We found a
      similar level of maximum quantum noise reduction for a first-order Laguerre
      Gaussian pump beam and a regular Gaussian pump beam, even though the optimal
      operational conditions differed in these two cases. Also, we investigated the
      effect of self-defocusing on the level of the vacuum squeezing by simultaneously
      monitoring the minimum quantum noise level and the output beam transverse profile
      at various pump laser powers and atomic densities and found no direct
      correlations between the increased beam size and the degree of measured
      squeezing. 

PMID- 24322145
TI  - High-energy noncollinear optical parametric-chirped pulse amplification in LBO at
      800 nm.
AB  - The optical parametric-chirped pulse amplification (OPCPA) based on large
      aperture nonlinear optical crystals is promising for implementation of an
      ultrahigh peak-power laser system of 10 PW and beyond. We demonstrated the
      highest energy broadband OPCPA at 800 nm, to the best of our knowledge, by using
      an 80 mm in diameter LiB(3)O(5)(LBO) amplifier, with an output energy of 28.68 J,
      a bandwidth of 80 nm (FWHM), and conversion efficiency of 25.38%. After
      compression, a peak power of 0.61 PW with 33.8 fs pulse duration is produced.

PMID- 24322146
TI  - Characterization of stimulated Brillouin scattering in a few-mode fiber.
AB  - Characterization of stimulated Brillouin scattering (SBS) in a few-mode fiber
      (FMF) is experimentally demonstrated, where the Brillouin gain spectrum (BGS) of
      intramodal or intermodal SBS is analyzed for different pump-probe pairs of four
      LP modes--LP(01), LP(11), LP(21), and LP(02) modes--guided in the fiber. A mode
      division multiplexer composed of concatenated mode-selective couplers is applied
      for selective launching of each LP mode, and a differential measurement scheme is
      adopted for the analysis of the BGS. The intermodal SBS is observed in each pump
      probe pair of different modes, and the Brillouin gain is measured to be within
      14%-45% of that of the SBS between the LP(01) modes. The SBS threshold of each LP
      mode in the FMF is also evaluated.

PMID- 24322147
TI  - Quantitative phase imaging via Fourier ptychographic microscopy.
AB  - Fourier ptychographic microscopy (FPM) is a recently developed imaging modality
      that uses angularly varying illumination to extend a system's performance beyond
      the limit defined by its optical components. The FPM technique applies a novel
      phase-retrieval procedure to achieve resolution enhancement and complex image
      recovery. In this Letter, we compare FPM data to theoretical prediction and phase
      shifting digital holography measurement to show that its acquired phase maps are
      quantitative and artifact-free. We additionally explore the relationship between
      the achievable spatial and optical thickness resolution offered by a
      reconstructed FPM phase image. We conclude by demonstrating enhanced
      visualization and the collection of otherwise unobservable sample information
      using FPM's quantitative phase. 

PMID- 24322148
TI  - Suppression of free carrier absorption in silicon using multislot SiO2/nc-Si
      waveguides.
AB  - Free carrier absorption (FCA) in silicon is the major obstacle toward achieving
      optical gain in Si nanostructure systems. In this Letter, we present experimental
      results of pump-induced loss for TE and TM polarization in multislot SiO2/nc-Si
      waveguides. Continuous wavelength and ultrafast studies of carriers excited in
      the nc-Si multilayers reveal strong suppression of transmission loss related to
      FCA in Si nanostructures for TM-polarized probe light. We demonstrate
      theoretically and experimentally that FCA may be reduced under TM polarization as
      much as 9 times compared to TE polarization.

PMID- 24322149
TI  - Broadband light coupling to dielectric slot waveguides with tapered plasmonic
      nanoantennas.
AB  - We propose and theoretically verify an efficient mechanism of broadband coupling
      between incident light and on-chip dielectric slot waveguide by employing a
      tapered plasmonic nanoantenna. The nanoantenna receives free space radiation and
      couples it to a dielectric slot waveguide with the efficiency of up to 20% in a
      broad spectral range, having a small footprint as compared with the currently
      used narrowband dielectric grating couplers. We argue that the frequency
      selective properties of such nanoantennas also allow for using them as ultrasmall
      on-chip multiplexer/demultiplexer devices. 

PMID- 24322150
TI  - Widely tunable single-bandpass microwave photonic filter based on polarization
      processing of a nonsliced broadband optical source.
AB  - We propose a new scheme of microwave photonic filter (MPF) based on the
      polarization processing of a broadband optical source (BOS), which features
      single-bandpass response and a wide span of operation bandwidth. The BOS is
      orthogonally polarized by a polarization division multiplexing emulator (PDME)
      with a tunable time delay between the two polarization states and incident at +/-
      45 degrees  to one principle axis of a polarization modulator (PolM). The PDME
      cascades a PolM, and a polarizer realizes a microwave modulation making the phase
      of the carrier able to be tuned while +/- 1st sidebands remain unchanged, which
      after propagating in a dispersive medium results in a tunable single-bandpass
      response in the RF domain. We experimentally verify the MPF. By adjusting the
      time delay and the optical spectrum bandwidth, the passband center frequency is
      continuously tuned from DC to 20 GHz and the 3 dB passband bandwidth changes
      while the optical spectrum bandwidth ranges from 1 to 4 nm.

PMID- 24322151
TI  - Photonic-plasmonic-coupled nanoantennas for polarization-controlled multispectral
      nanofocusing.
AB  - We report on the design and experimental demonstration of array-enhanced
      nanoantennas for polarization-controlled multispectral nanofocusing in the near
      IR spectral range. We design plasmonic double bow-tie nanoantennas-coupled to
      multiple-periodic nanoparticle arrays to harvest radiation of designed
      wavelengths from a large spatial area and to focus it into a targeted nanoscale
      region. Near-field calculations were performed on a gold nanoantenna array using
      three-dimensional finite difference time domain simulations. Cross-shaped optical
      nanoantennas were fabricated on glass substrates using electron beam lithography.
      The optical characterization of the fabricated nanoantennas was performed using
      second harmonic excitation spectroscopy that demonstrates multiwavelength
      photonic coupling in good agreement with the antenna modeling. The nanoantenna
      structures introduced in this Letter provide the ability to focus optical energy
      into deep subwavelength areas and to address multiple spectral regions with
      polarization control. Such attributes are highly desirable in optical biosensing,
      enhanced Raman scattering, and for nonlinear plasmonic applications. 

PMID- 24322152
TI  - Resolution upgrade toward 6-bit optical quantization using power-to-wavelength
      conversion for photonic analog-to-digital conversion.
AB  - We demonstrate a resolution upgrade toward 6 bit optical quantization using a
      power-to-wavelength conversion without an increment of system parallelism.
      Expansion of a full-scale input range is employed in conjunction with reduction
      of a quantization step size with keeping a sampling-rate transparency
      characteristic over several 100 sGS/s. The effective number of bits is estimated
      to 5.74 bit, and the integral nonlinearity error and differential nonlinearity
      error are estimated to less than 1 least significant bit.

PMID- 24322153
TI  - 1.06-MUm InGaAs/GaAs multiple-quantum-well optical thyristor lasers with a PiNiN
      structure.
AB  - InGaAs/GaAs multiple quantum well (MQW)-depleted optical thyristor lasers
      operating at 1.06 MUm with a waveguide-type PiNiN structure is presented for the
      first time. The optical thyristor lasers clearly show nonlinear S-shaped current
      voltage and lasing characteristics. The measured switching voltage and current
      are 5 V and 1 mA, respectively. The holding voltage and current are 2.6 V and 3.6
      mA, respectively. A relatively high output light power of 30 mW per facet at room
      temperature is achieved. The lasing wavelength is 1.055 MUm at a bias current of
      80 mA at 25  degrees C.

PMID- 24322154
TI  - Spectral modulation of high-order harmonic generation from prealigned CO2
      molecules.
AB  - We demonstrate experimentally that prealigned molecules produce observable
      spectral redshift or blueshift on the high-order harmonic generation. We
      distinguish two effects of molecular alignment on the phase modulation of the
      harmonics; one is from the gradient of alignment degree and the other is the
      plasma density varied by the molecular alignment. The finding provides an insight
      on the spectral distribution of molecular harmonics and a method of fine-tuning
      the harmonic spectrum. 

PMID- 24322155
TI  - Strong three-dimensional field localization and enhancement on deep sinusoidal
      gratings with two-dimensional periodicity.
AB  - The study of total light absorption due to excitation of localized surface
      plasmons on deep metallic crossed gratings having a sinusoidal profile with a two
      dimensional periodicity shows a very strong increase in the electric field
      intensity, reaching 800 times the incident intensity. The region with high
      intensity is strongly localized at the groove top and is characterized by a
      volume much smaller than the diffraction limit, both in transverse direction
      along the grating plane, and in longitudinal direction when going away from the
      grating surface. The field enhancement and its localization are much more
      pronounced than in shallow gratings. 

PMID- 24322156
TI  - Conservative and PT-symmetric compactons in waveguide networks.
AB  - Stable discrete compactons in interconnected three-line waveguide arrays are
      found in linear and nonlinear limits in conservative and in parity-time (PT)
      symmetric models. The compactons result from the interference of the fields in
      the two lines of waveguides ensuring that the third (middle) line caries no
      energy. PT-symmetric compactons require not only the presence of gain and losses
      in the two lines of the waveguides but also complex coupling, i.e., gain and
      losses in the coupling between the lines carrying the energy and the third line
      with zero field. The obtained compactons can be stable and their branches can
      cross the branches of the dissipative solitons. Unusual bifurcations of branches
      of solitons from linear compactons are described. 

PMID- 24322157
TI  - Quantum simulation of decoherence in optical waveguide lattices.
AB  - We suggest that propagation of nonclassical light in lattices of optical
      waveguides can provide a laboratory tool to simulate quantum decoherence
      phenomena with high non-Markovian features. As examples, we study decoherence of
      optical Schrodinger cats in a lattice that mimics a dissipative quantum harmonic
      oscillator coupled to a quantum bath, showing fractional decoherence in the
      strong coupling regime, and Bloch oscillations of optical Schrodinger cats, where
      damped revivals of the coherence can be observed. 

PMID- 24322158
TI  - Empirical model of total internal reflection from highly turbid media.
AB  - We demonstrate, to the best of our knowledge, a first accurate empirical model
      for reflectance measurements from highly turbid media over the full range of
      incident angles, i.e., for reflectivity values going from unity in the total
      internal reflection regime to nearly zero when almost all the light is
      transmitted. Evidence that our model is accurate is provided by extraction of the
      particle size, followed by independent verification with dynamic light
      scattering. Our methodology is in direct contrast with the prevalent approach in
      turbid media of focusing on only the critical angle region, which is just a small
      subset of the entire reflectance data. 

PMID- 24322159
TI  - High-speed ultrawideband photonically enabled compressed sensing of sparse radio
      frequency signals.
AB  - We demonstrate a new architecture for high-speed compressed sensing using chirp
      processing with ultrafast laser pulses, presently applied to the measurement of
      sparse-frequency microwave signals. We spectrally encode highly chirped ultrafast
      laser pulses with pseudorandom bit sequences such that every laser pulse acquires
      a unique spectral pattern. The pulses are partially compressed in time, extending
      the effective sampling rate beyond the electronic limit, and then modulated with
      a sparse microwave signal. Finally the pulses are fully compressed and detected,
      effectively integrating the measurement. We achieve 100 usable features per
      pattern allowing for 100 points in the reconstructed microwave spectra and
      experimentally demonstrate reconstruction of two- and three-tone microwave
      signals spanning from 900 MHz to 14.76 GHz. These spectra are reconstructed by
      measuring the energy of only 23 to 38 consecutive laser pulses acquired in a
      single shot with a 500 MHz real-time oscilloscope.

PMID- 24322160
TI  - White light lateral shear interferometer with holographic shear lenses and
      spatial Fourier transform.
AB  - Lateral shear interferometer is a simple yet powerful method for testing
      wavefronts or measuring refractive index changes. Previously, we have reported a
      method of using two holographic lenses to obtain shear and to generate a spatial
      frequency carrier, which was used for quantitative analysis. This technique has
      some advantages such as stability and instantaneous measurements. In this Letter,
      we report a method of using white light with holographic gratings to obtain shear
      and also to perform wavefront analysis using the spatial carrier fringes
      generated at a specific selected wavelength from the white light spectrum. We
      show that the sensitivity of the setup can be changed by selecting different
      wavelengths from the spectrum. 

PMID- 24322161
TI  - Wideband optical vector network analyzer based on optical single-sideband
      modulation and optical frequency comb.
AB  - A novel approach to increase the measurement range of the optical vector network
      analyzer (OVNA) based on optical single-sideband (OSSB) modulation is proposed
      and experimentally demonstrated. In the proposed system, each comb line in an
      optical frequency comb (OFC) is selected by an optical filter and used as the
      optical carrier for the OSSB-based OVNA. The frequency responses of an optical
      device-under-test (ODUT) are thus measured channel by channel. Because the comb
      lines in the OFC have fixed frequency spacing, by fitting the responses measured
      in all channels together, the magnitude and phase responses of the ODUT can be
      accurately achieved in a large range. A proof-of-concept experiment is performed.
      A measurement range of 105 GHz and a resolution of 1 MHz is achieved when a five
      comb-line OFC with a frequency spacing of 20 GHz is applied to measure the
      magnitude and phase responses of a fiber Bragg grating. 

PMID- 24322162
TI  - Robust frequency stabilization of multiple spectroscopy lasers with large and
      tunable offset frequencies.
AB  - We have demonstrated a compact, robust device for simultaneous absolute frequency
      stabilization of three diode lasers whose carrier frequencies can be chosen
      freely relative to the reference. A rigid ULE multicavity block is employed, and,
      for each laser, the sideband locking technique is applied. A small lock error,
      computer control of frequency offset, wide range of frequency offset, simple
      construction, and robust operation are the useful features of the system. One
      concrete application is as a stabilization unit for the cooling and trapping
      lasers of a neutral-atom lattice clock. The device significantly supports and
      improves the clock's operation. The laser with the most stringent requirements
      imposed by this application is stabilized to a line width of 70 Hz, and a
      residual frequency drift less than 0.5 Hz/s. The carrier optical frequency can be
      tuned over 350 MHz while in lock.

PMID- 24322163
TI  - Fast mapping of absorbing defects in optical materials by full-field photothermal
      reflectance microscopy.
AB  - We report a technique for rapidly mapping absorbing defects in optical materials,
      which act as laser-induced damage precursors, based on full-field photothermal
      reflectance microscopy. An intensity-modulated pump beam heats absorbing defects
      in the optical sample, creating localized, modulated refractive-index variations
      around the defects. A probe beam then illuminates the defect sites, and the
      measured amplitude of the reflectance variation is used to map the distribution
      of defects in the medium. Measurements show that this method offers a faster
      defect mapping speed of about 0.03 mm(2) per minute and a detectivity of a few
      tens of nanometers comparable to that of conventional scanning photothermal
      deflection microscopy.

PMID- 24322164
TI  - Surface plasmon resonance sensor interrogation with a double-clad fiber coupler
      and cladding modes excited by a tilted fiber Bragg grating.
AB  - We present a novel optical fiber surface plasmon resonance (SPR) sensor scheme
      using reflected guided cladding modes captured by a double-clad fiber coupler and
      excited in a gold-coated fiber with a tilted Bragg grating. This new
      interrogation approach, based on the reflection spectrum, provides an improvement
      in the operating range of the device over previous techniques. The device allows
      detection of SPR in the reflected guided cladding modes and also in the
      transmitted spectrum, allowing comparison with standard techniques. The sensor
      has a large operating range from 1.335 to 1.432 RIU, and a sensitivity of 510.5
      nm/RIU. The device shows strong dependence on the polarization state of the
      guided core mode which can be used to turn the SPR on or off.

PMID- 24322165
TI  - Design and demonstration of high quality-factor H1-cavity in two-dimensional
      photonic crystal.
AB  - We introduce a method for designing an H1 photonic crystal cavity to enhance its
      quality factor (Q factor). The highest theoretical Q factor of 120,000 is
      obtained. The Fourier transformation of field distribution shows that the
      enhancement arises from the component reduction of a leaky mode. The Q-factor
      improvement has also been demonstrated experimentally with the highest value of
      11,700. Our design could be useful for studying light-matter interaction in an H1
      cavity as the mode volume only increases slightly. 

PMID- 24322166
TI  - Dynamics of microparticles trapped in a perfect vortex beam.
AB  - We analyze microparticle dynamics within a "perfect" vortex beam. In contrast to
      other vortex fields, for any given integer value of the topological charge, a
      "perfect" vortex beam has the same annular intensity profile with fixed radius of
      peak intensity. For a given topological charge, the field possesses a well
      defined orbital angular momentum density at each point in space, invariant with
      respect to azimuthal position. We experimentally create a perfect vortex and
      correct the field in situ, to trap and set in motion trapped microscopic
      particles. For a given topological charge, a single trapped particle exhibits the
      same local angular velocity moving in such a field independent of its azimuthal
      position. We also investigate particle dynamics in "perfect" vortex beams of
      fractional topological charge. This light field may be applied for novel studies
      in optical trapping of particles, atoms, and quantum gases. 

PMID- 24322167
TI  - Calibration of optical traps by dual trapping of one bead.
AB  - We introduce a method for optical trap calibration that is suitable for
      viscoelastic material. The method is designed for use on experimental setups with
      two optical tweezers and is based on pulling a trapped particle with one trap
      while holding it with the other. No piezo stage is needed, and only one optical
      trap must be movable with galvo mirrors, piezo mirrors, or acousto-optical
      deflectors. The method combines advantages of commonly known PSD-fitting and fast
      sweeping methods, allowing calibration of a completely fixed trap in a fluid of
      unknown viscosity/viscoelasticity. A detailed method description, a theoretical
      derivation, and an experimental comparison to other methods are reported. 

PMID- 24322168
TI  - 3 GHz, Yb-fiber laser-based, few-cycle ultrafast source at the Ti:sapphire laser
      wavelength.
AB  - We demonstrate a compact ultrafast source centered at 850 nm with >200 nm
      bandwidth (full width at half-maximum) based on a 3 GHz Yb-fiber master
      oscillator-power-amplifier system. The output pulses (with up to 13 W average
      power) from the laser system are coupled into short (<50 mm) pieces of photonic
      crystal fibers to excite broadband fiber-optic Cherenkov radiation; the resulting
      broad phase-matching bandwidth due to short fiber length produces an upconverted
      spectrum spanning in the wavelength range of 750-950 nm with average power of 94,
      184, and 380 mW for fiber length of 28, 37, and 48 mm, respectively. The spectrum
      generated from the 37 mm fiber is then dechirped by eight double-chirped mirrors,
      leading to compressed pulses ~14 fs in duration. Such an ultrafast source is a
      promising substitute of multigigahertz mode-locked Ti:sapphire lasers for
      applications in optical frequency metrology and multiphoton coherent microscopy.

PMID- 24322169
TI  - Wide optical spectrum range, subvolt, compact modulator based on an electro-optic
      polymer refilled silicon slot photonic crystal waveguide.
AB  - We design and demonstrate a compact and low-power, band-engineered, electro-optic
      (EO) polymer refilled silicon slot photonic crystal waveguide (PCW) modulator.
      The EO polymer is engineered for large EO activity and near-infrared
      transparency. A PCW step coupler is used for optimum coupling to the slow-light
      mode of the band-engineered PCW. The half-wave switching voltage is measured to
      be Vpi = 0.97 +/- 0.02 V over an optical spectrum range of 8 nm, corresponding to
      the effective in-device r(33) of 1199 pm/V and V(pi) * L = 0.291 +/- 0.006 V * mm
      in a push-pull configuration. Excluding the slow-light effect, we estimate that
      the EO polymer is poled with an efficiency of 89 pm/V in the slot.

PMID- 24322170
TI  - Strongly increased exposure of meloxicam in CYP2C9*3/*3 individuals.
AB  - OBJECTIVE: The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics
      and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects.
      METHODS: After oral administration of 15 mg meloxicam, the plasma concentrations
      of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3
      individuals, and three CYP2C9*3/*3 individuals. The pharmacodynamic effects were
      determined by measuring thromboxane B2 generated in blood. RESULTS: A nine-fold
      lower apparent oral clearance and an eight-fold higher AUC0-infinity of single
      dose meloxicam were observed in CYP2C9*3/*3 individuals when compared with
      CYP2C9*1/*1 individuals. CYP2C9*3/*3 individuals also showed markedly increased
      inhibition of thromboxane B2 generation by meloxicam. CONCLUSION: These results
      indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration
      dependent adverse effects during long-term treatment with standard doses of
      meloxicam.

PMID- 24322172
TI  - Brain development and scholastic achievement in the Education Quality Measurement
      System tests in Chilean school-aged children.
AB  - BACKGROUND: Head circumference (HC), the anthropometric index of both brain
      development and nutritional background, has been described to be significantly
      associated with scholastic achievement (SA). The aim of this study was to
      determine the impact of nutritional background and current nutritional status
      parameters on SA in the Education Quality Measurement System (SIMCE) tests.
      METHODS: A representative sample of 33 schools was randomly chosen in the
      Metropolitan Region of Chile. The sample consisted of 1,353 school-aged children
      of both sexes, from the fifth grade of elementary school and from the first grade
      of high school who in 2009 took the SIMCE tests. Nutritional status was assessed
      through anthropometric parameters. Brain development was measured through the HC
      expressed as HC-for-age Z-score (Z-HC). RESULTS: Students with Z-HC < -2 SD and
      >2 SD obtained low and high SA, respectively, both in the language and the
      mathematics tests (P < 0.001). In general, in both grades, those students with Z
      HC >= 0 SD increase more than double the probability to obtain language and
      mathematics SA scores >= the median (P < 0.0001). CONCLUSION: We confirm the
      hypothesis that HC is the most relevant physical index associated with SA;
      therefore, children with the lowest scores in the SIMCE tests probably have lower
      brain development.

PMID- 24322173
TI  - Multiply-twinned intermetallic AuCu pentagonal nanorods.
AB  - Monodispersed intermetallic AuCu pentagonal nanorods with controlled size and
      composition have been developed by a seed-mediated growth route. The AuCu/C
      nanomaterial catalyzed the coupling reaction of sulfonamide with benzyl alcohol
      in good to excellent yields. 

PMID- 24322174
TI  - SIRT3 expression as a biomarker for better prognosis in gastric cancer.
AB  - BACKGROUND: SIRT3-mitochondrial nicotinamide adenine dinucleotide-dependent
      deacetylase sirtuin-3-plays an important role in regulating cell metabolism and
      carcinogenesis. The role of SIRT3 in gastric cancer has not yet been
      investigated. METHODS: A total of 221 gastric cancer patients who underwent
      curative surgery were enrolled at the Department of Surgery, Taipei Veterans
      General Hospital. SIRT3 expression in gastric tissues and tumors were examined in
      these patients using immunohistochemical staining. Clinicopathologic
      characteristics and survival were analyzed and compared in gastric cancer
      patients with or without SIRT3 expression. RESULTS: The 5-year survival rates of
      patients with or without SIRT3 expression were 51.2 and 39.1 %, respectively (p =
      0.005). The 5-year disease-free survival rates of patients with or without SIRT3
      expression were 49.6 and 38.0 %, respectively (p = 0.010). Microscopic features
      showed that there are more poor cell differentiation (p = 0.001), more diffuse
      type Lauren's histology (p = 0.018), and more scirrhous-type stromal reactions (p
      = 0.027) in gastric cancer without SIRT expression. Multivariate analysis with
      overall survival as an endpoint showed that age (p < 0.001), Lauren's histology
      (p = 0.007), stromal reaction (p = 0.035), TNM pathologic N category (p < 0.001),
      and SIRT3 expression (p < 0.001) were significantly correlated with gastric
      cancer. CONCLUSIONS: Gastric cancer patients with SIRT3 expression have a better
      prognosis than those without. SIRT3 expression is an independent prognostic
      marker for overall survival and may act as a tumor suppressor in gastric cancer.

PMID- 24322175
TI  - Role of SDHAF2 and SDHD in von Hippel-Lindau associated pheochromocytomas.
AB  - BACKGROUND: Pheochromocytomas (PCCs) develop from the adrenal medulla and are
      often part of a hereditary syndrome such as von Hippel-Lindau (VHL) syndrome. In
      VHL, only about 30 % of patients with a VHL missense mutation develop PCCs. Thus,
      additional genetic events leading to formation of such tumors in patients with
      VHL syndrome are sought. SDHAF2 (previously termed SDH5) and SDHD are both
      located on chromosome 11q and are required for the function of mitochondrial
      complex II. While SDHAF2 has been shown to be mutated in patients with
      paragangliomas (PGLs), SDHD mutations have been found both in patients with PCCs
      and in patients with PGLs. MATERIALS AND METHODS: Because loss of 11q is a common
      event in VHL-associated PCCs, we aimed to investigate whether SDHAF2 and SDHD are
      targets. In the present study, 41 VHL-associated PCCs were screened for mutations
      and loss of heterozygosity (LOH) in SDHAF2 or SDHD. Promoter methylation, as well
      as mRNA expression of SDHAF2 and SDHD, was studied. In addition,
      immunohistochemistry (IHC) of SDHB, known to be a universal marker for loss of
      any part the SDH complex, was conducted. RESULTS AND CONCLUSIONS: LOH was found
      in more than 50 % of the VHL-associated PCCs, and was correlated with a
      significant decrease (p < 0.05) in both SDHAF2 and SDHD mRNA expression, which
      may be suggestive of a pathogenic role. However, while SDHB protein expression as
      determined by IHC in a small cohort of tumors was lower in PCCs than in the
      surrounding adrenal cortex, there was no obvious correlation with LOH or the
      level of SDHAF2/SDHD mRNA expression. In addition, the lack of mutations and
      promoter methylation in the investigated samples indicates that other events on
      chromosome 11 might be involved in the development of PCCs in association with
      VHL syndrome.

PMID- 24322176
TI  - Evaluation of modified estimation of physiologic ability and surgical stress in
      patients undergoing surgery for choledochocystolithiasis.
AB  - BACKGROUND: The incidence of complicated choledochocystolithiasis is increasing
      with the aging of society in Japan. We evaluated the utility of our prediction
      rule modified estimation of physiologic ability and surgical stress (mE-PASS) in
      predicting postoperative adverse events in patients with
      choledochocystolithiasis. METHODS: A total of 4,329 patients who underwent
      elective surgery for choledochocystolithiasis in 44 referral hospitals between
      April 1987 and April 2007 were analyzed for mE-PASS along with postoperative
      events. The discrimination power of mE-PASS was assessed by the area under the
      receiver operating characteristic curve (AUC). The correlation between ordinal
      and interval variables was quantified by the Spearman rank correlation (rho). The
      ratio of observed-to-estimated mortality rates (OE ratio) was used as a metric of
      surgical quality. RESULTS: Postoperative in-hospital mortality rates were 0 %
      (0/3,442) for laparoscopic cholecystectomy, 0.19 % (1/521) for open
      cholecystectomy, 1.6 % (1/63) for laparoscopic choledochotomy, 1.1 % (3/264) for
      open choledochotomy, and 5.1 % (2/39) for plasty or resection of the common bile
      duct. mE-PASS demonstrated a high discrimination power to predict in-hospital
      mortality; AUC, 95 % confidence interval (CI) of 0.96, 0.94-0.99. The predicted
      mortality rates significantly correlated with the severity of postoperative
      complications (rho = 0.278, p < 0.0001) and length of hospital stay (rho = 0.479,
      p < 0.0001). The OE ratios (95 % CI) improved slightly over time; 1.5 (0.25-9.0)
      between 1987 and 2000, and 0.40 (0.078-2.1) between 2001 and 2007. CONCLUSIONS:
      The present study suggests that mE-PASS can predict postoperative risks in
      patients who have undergone choledochocystolithiasis. mE-PASS may be useful in
      surgical decision making and evaluating the quality of care.

PMID- 24322171
TI  - Apolipoprotein E genotype and outcome in infants with hypoxic-ischemic
      encephalopathy.
AB  - BACKGROUND: Adults with the apolipoprotein E (APOE) gene alleles e4 and e2 are at
      high risk of poor neurological outcome after brain injury. The e4 allele has been
      associated with cerebral palsy (CP), and the e2 allele has been associated with
      worse neurological outcome with congenital heart disease. This study was done to
      test the hypothesis that the APOE genotype is associated with outcome among
      neonates who survive after hypoxic-ischemic encephalopathy (HIE). METHODS: We
      conducted a cohort study of infants who survived HIE and had 18-22 mo
      standardized neurodevelopmental evaluations to assess associations between
      disability and the APOE genotypes e3/e3, e4/-, and e2/-. RESULTS: A total of 139
      survivors were genotyped. Of these, 86 (62%) were of the e3/e3, 41 (29%) were of
      the e4/-, and 14 (10%) were of the e2/- genotypes. One hundred and twenty-nine
      infants had genotype and follow-up data; 26% had moderate or severe disabilities.
      Disability prevalence was 30 and 19% among those with and without the e3/e3
      genotype, 25 and 26% among those with and without the e2 allele, and 18 and 29%
      among those with and without the e4 allele, respectively. None of the differences
      were statistically significant. CP prevalence was also similar among genotype
      groups. CONCLUSION: Disability was not associated with the APOE genotype in this
      cohort of HIE survivors.

PMID- 24322178
TI  - Obstructive sleep apnoea does not lead to clinically significant erythrocytosis.

PMID- 24322177
TI  - Is current perioperative practice in hepatic surgery based on enhanced recovery
      after surgery (ERAS) principles?
AB  - BACKGROUND: The worldwide introduction of multimodal enhanced recovery programs
      has also changed perioperative care in patients who undergo liver resection. This
      study was performed to assess current perioperative practice in liver surgery in
      11 European HPB centers and compare it to enhanced recovery after surgery (ERAS)
      principles. METHODS: In each unit, 15 consecutive patients (N = 165) who
      underwent hepatectomy between 2010 and 2012 were retrospectively analyzed.
      Compliance was classified as "full," "partial," or "poor" whenever >= 80, >= 50,
      or <50 % of the 22 ERAS protocol core items were met. The primary study end point
      was overall compliance with the ERAS core program per unit and per perioperative
      phase. RESULTS: Most patients were operated on for malignancy (91 %) and 56 %
      were minor hepatectomies. The median number of implemented ERAS core items was 9
      (range = 7-12) across all centers. Compliance was partial in the preoperative
      (median 2 of 3 items, range = 1-3) and perioperative phases (median 5 of 10
      items, range: 4-7). Median postoperative compliance was poor (median 2 of 9
      items, range = 0-4). A statistically significant difference was observed between
      median length of stay and median time to recovery (7 vs. 5 days, P < 0.001).
      CONCLUSION: Perioperative care among centers that perform liver resections varied
      substantially. In current HPB surgical practice, some elements of the ERAS
      program, e.g., preoperative counselling and minimal fasting, have already been
      implemented. Elements in the perioperative phase (avoidance of drains and
      nasogastric tube) and postoperative phase (early resumption of oral intake, early
      mobilization, and use of recovery criteria) should be further optimized.

PMID- 24322181
TI  - New technologies for measuring single cell mass.
AB  - Characterizing the physical properties of single cells is of great interest for
      unraveling the heterogeneity in a cell population. Recent advances in micro
      systems technologies and quantitative imaging have enabled measurements of the
      mass and growth of single cells. So far, three classes of techniques have been
      reported for such measurements. These are suspended micro-channel resonators
      (SMR) sensors, quantitative phase imaging (QPI), and pedestal resonant sensors.
      Here we compare the unique merits of each method and discuss their potential to
      evolve into multi-modal platforms for answering fundamental questions in biology
      and medicine. 

PMID- 24322179
TI  - Immunotherapy of tumor with vaccine based on basic fibroblast growth factor
      activated fibroblasts.
AB  - PURPOSE: Cancer-associated fibroblasts play a key role in tumor progression. It
      is conceivable that the breaking of immune tolerance of "self-antigens"
      associated with tumor cells and tumor stromal is an attractive approach for tumor
      immunotherapy. To test this concept, we used basic fibroblast growth factor
      (bFGF) to activate normal fibroblasts and used these activated fibroblasts as one
      vaccine against tumor. METHODS: Normal fibroblasts were treated with bFGF; their
      expressions of a-SMA and FAP were assessed by Western blot. We immunized mice
      with bFGF-activated fibroblasts. Auto-antibodies were assessed by flow cytometric
      and Western blot analysis. The deposition of auto-antibodies within the tumor
      tissues was assessed. The inhibition of proliferation of tumor cells and
      fibroblasts by purified immunoglobulins was investigated. The anti-tumor effects
      of purified immunoglobulins and lymphocytes of immunized mice were assessed.
      RESULTS: The bFGF-activated fibroblasts were effective in affording protection
      from tumor onset, growth, and prolonging survival of tumor-bearing mice. The
      immunized sera exhibited positive staining for fibroblasts and tumor cells in
      FCAS and Western blot analysis. The purified immunoglobulins of immunized serum
      could inhibit the proliferation of tumor cells and fibroblasts in vitro and had
      the anti-tumor activity in vivo. There was the deposition of auto-antibodies
      within the tumor tissues. Adoptive transfer of lymphocytes of immunized mice
      revealed that cellular immune response is also involved. The anti-tumor activity
      could be abrogated by the depletion of CD4(+), CD8(+) T lymphocytes and NK cells.
      CONCLUSIONS: In summary, bFGF-activated fibroblasts could induce an autoimmune
      response which was simultaneously against both cancer-associated fibroblasts and
      tumor cells in a cross-reaction.

PMID- 24322180
TI  - Induction of antigen-specific immune responses by dendritic cells transduced with
      a recombinant lentiviral vector encoding MAGE-A3 gene.
AB  - PURPOSE: Melanoma antigen gene A3 (MAGE-A3) is aberrantly expressed in a number
      of cancer types. Because of its high specificity, MAGE-A3 has shown to be a
      promising candidate for cancer immunotherapy. Dendritic cells (DCs) have emerged
      as the natural agents for antigen delivery. DCs transduced with antigen may
      increase immune response and maintain immune durability. The aim of this study
      was to investigate the roles of DCs transduced with lentiviral vectors (LVs)
      encoding full-length MAGE-A3 gene in cancer immunotherapy . METHODS: A LV
      containing full-length MAGE-A3 gene (rLV/MAGE-A3) was constructed. Reverse
      transcriptase-polymerase chain reaction and direct DNA sequencing were performed
      to verify the construct. Human DCs derived from umbilical cord blood were then
      transduced with rLV/MAGE-A3. The potency of rLV/MAGE-A3-transduced DCs was
      examined by measurement of surface markers and mixed lymphocyte reaction. The
      MAGE-A3-specific T-cell response induced by DCs was detected using the lactate
      dehydrogenase release assay. RESULTS: rLV/MAGE-A3 was constructed successfully
      and used to transduce DCs efficiently. DCs transduced with rLV/MAGE-A3 stably
      expressed MAGE-A3 and yielded high percentage of cells expressing CD80, CD86, and
      HLA-DR. rLV/MAGE-A3 transduction did not impair DCs viability and maturation at a
      multiplicity of infection of 30. The rLV/MAGE-A3-transduced DCs induced MAGE-A3
      specific T lymphocytes that exhibited a significant lysis activity against MAGE
      A3-bearing tumor cell lines (HuH-7 and SGC-7901). CONCLUSIONS: DC-directed
      rLV/MAGE-A3 efficiently induced antigen-specific immune responses, indicating the
      possibility of DC-based MAGE-A3 antigen vaccine as a promising strategy for
      treatment of MAGE-A3-associated cancer.

PMID- 24322182
TI  - Correction of vitamin D insufficiency with combined strontium ranelate and
      vitamin D3 in osteoporotic patients.
AB  - OBJECTIVE: This study aims to investigate the efficacy and safety of oral fixed
      dose combination of strontium ranelate 2  g/vitamin D3 1000  IU daily vs
      strontium ranelate 2  g daily for correcting vitamin D insufficiency in
      osteoporosis. DESIGN: A 6-month international, randomized, double-blind, parallel
      group, phase 3 study. METHODS: A total of 518 men and postmenopausal women aged
      >=50 years with primary osteoporosis (T-score <=-2.5 s.d.) and serum 25
      hydroxyvitamin D (25(OH)D) >22.5 nmol/l were included. Patients were allocated to
      strontium ranelate 2 g/vitamin D3 1000  IU daily (n=413) or strontium ranelate 2
      g daily (n=105). The participants received calcium 1 g daily. The primary
      endpoint was serum 25(OH)D at last post-baseline evaluation during 3 months.
      RESULTS: Both groups were comparable at baseline. Mean baseline of 25(OH)D was
      44.1 +/- 14.6 nmol/l. After 3 months, the percentage of patients with 25(OH)D
      >=50 nmol/l was higher with strontium ranelate/vitamin D3 vs strontium ranelate
      (84 vs 44%, P<0.001; adjusted between-group odds ratio=6.7; 95% CI, 4.2-10.9).
      The efficacy of the fixed-dose combination on 25(OH)D was maintained at 6 months
      (86 vs 40%, P<0.001). Mean 25(OH)D was 65.1 and 49.5 nmol/l, respectively, after
      3 months and 66.9 and 45.4 nmol/l after 6 months. Physical performance improved
      in both groups. Falls were 17 and 20% in the strontium ranelate/vitamin D3 and
      strontium ranelate groups respectively. Parathyroid hormone levels were inversely
      correlated with 25(OH)D. No clinically relevant differences in safety were
      observed. CONCLUSIONS: This study confirms the efficacy and safety of fixed-dose
      combination of strontium ranelate 2 g/vitamin D3 1000 IU for correction of
      vitamin D insufficiency in osteoporotic patients.

PMID- 24322183
TI  - Increasing prevalence of Addison's disease in German females: health insurance
      data 2008-2012.
AB  - OBJECTIVE: Our objective was to investigate the epidemiology of autoimmune
      Addison's disease (AD) in Germany. DESIGN: Routine data were analyzed from the
      Statutory Health Insurance (SHI) database of the Techniker Krankenkasse (TK) for
      an observation period from 01/01/2008 to 31/12/2012. The TK is one of the largest
      German health care insurance providers covering more than 10% of the German
      population. SUBJECTS AND METHODS: Between 2008 and 2012, a total of 2477
      diagnoses of primary adrenal failure were recorded in the SHI database. After
      exclusion of secondary, iatrogenic or other non-idiopathic forms and after
      adjustment for incomplete data sets, 1364 diagnoses of autoimmune-mediated AD
      remained. RESULTS: The prevalence of AD in our cohort showed a steady increase
      from 82 per million in 2008 to 87 per million in 2012. On average, the prevalence
      rose about 1.8% per year, and due to a pronounced increase (2.7%) in females. The
      prevalence was lower in men (63-68 per million) than in women (96-108 per
      million). Autoimmune comorbidities were found in 46.5% of AD patients. Adrenal
      crises were documented with a frequency of 14-17/100 patient years. CONCLUSIONS:
      These data provide a first epidemiological profile of this rare and perilous
      endocrine disease in Germany. Although the prevalence of AD appears lower than in
      the Scandinavian countries, the increasing figures in females over the last 5
      years warrant further investigations. Furthermore, adrenal crises pose a
      considerable burden. Hereby, we can show that health insurance data provide a
      valuable tool for epidemiological studies in the absence of national registries.

PMID- 24322184
TI  - Thoughts on paper, the present and the future.

PMID- 24322185
TI  - Early functional results of biofeedback and its impact on quality of life of
      patients with anal incontinence.
AB  - CONTEXT: Biofeedback has been used successfully in the treatment of fecal
      incontinence, working mainly on rehabilitation of the sphincter muscle. However,
      there are few studies presenting objective results of biofeedback, in terms of
      functional results and those related to the quality of life. OBJECTIVES: The aims
      of this study was to evaluate the immediate results of biofeedback in the
      treatment of fecal incontinence and its impact on the quality of life of patients
      by using validated questionnaires, correlating the results with those related to
      functional parameters of quality of life and clinical variables. METHODS: We
      analyzed and compared the results of biofeedback in 52 patients with fecal
      incontinence before the start of the sessions and immediately after the end of
      them, by applying validated questionnaires assessing the degree of intensity of
      fecal incontinence (FISI - Fecal Incontinence Severity Index) and evaluation of
      quality of life related to fecal incontinence (FIQL - Faecal Incontinence Quality
      of Life Scale) as compared to clinical variables (age, onset of symptoms,
      etiology of the fecal incontinence, number of sessions of biofeedback and number
      and types of deliveries). RESULTS: The evaluation of the results of FISI showed a
      significant increase in the number of individuals who had low severity scores of
      symptoms before and after the biofeedback (from 48.1 to 65.4%) with P = 0.004.
      There was significant improvements in domains of the FIQL, behavior (P = 0.008),
      depression (P = 0.006) and embarrassment (P = 0.008) after biofeedback. There was
      no significant correlation between the improvement of functional parameters
      evaluated by FISI and the improvement of quality of life. Positive correlation
      was found between the improvements of the domains of FIQL. There was no
      significant correlation between the results obtained using the FISI and FIQL with
      clinical variables assessed. CONCLUSIONS: Biofeedback has proven to be an
      effective therapy in the treatment of fecal incontinence, improving symptoms
      and/or quality of life for most patients, regardless of clinical presentation of
      this functional disorder.

PMID- 24322186
TI  - Role of Helicobacter pylori infection and lifestyle habits in the development of
      gastroduodenal diseases in a population from the Brazilian Amazon.
AB  - CONTEXT: Although more than half of the world's population is colonized with
      Helicobacter pylori, it remains unknown why this organism is able to produce
      severe disease in some hosts and be innocuous in others. The clinical outcome of
      infection is determined by several factors, including differences in the host
      response to bacterial stimulation, specific virulence factors of the organism and
      environmental influences, or a combination of these factors. OBJECTIVES: This
      study compared the prevalence of H. pylori infection and risk factors (infection
      with CagA+ strains, excessive alcohol consumption, smoking, and inadequate eating
      habits) between patients with different gastrointestinal disorders and associated
      these risk factors with the histopathological findings. METHODS: In a prospective
      study, samples were collected from 442 patients and a standardized questionnaire
      regarding lifestyle habits (excessive alcohol consumption, smoking, and eating
      habits) was applied. The presence of H. pylori and of the cagA gene was
      investigated by polymerase chain reaction (PCR). Gastric biopsies were obtained
      for histological assessment. RESULTS: The frequency of alcohol consumption,
      smoking, inadequate diet and infection with CagA+ H. pylori was higher among
      patients with peptic ulcer and adenocarcinoma when compared to those with
      gastritis. Gastric inflammation was more pronounced in patients infected with
      CagA+ strains. CONCLUSION: We conclude that infection with CagA+ H. pylori
      strains, excessive alcohol consumption, smoking and inadequate eating habits
      increase the risk of developing peptic ulcer and gastric carcinoma.

PMID- 24322187
TI  - Are the spider angiomas skin markers of hepatopulmonary syndrome?
AB  - CONTEXT: Hepatopathies can significantly influence both veins and arteries, these
      changes may cause some cutaneous stigmas, such as spider angioma (SA) and some
      systemic vascular changes, such as those observed in hepatopulmonary syndrome
      (HPS). Based on this common pathophysiological root we can assume that the SA can
      be skin markers of HPS. OBJECTIVE: The objective of this study is to assess
      whether there is a relationship between the presence of SA and HPS. METHODS:
      Records of 40 patients with liver cirrhosis who underwent contrast
      echocardiography were evaluated, in which we researched the description of SA,
      physical examination, and other clinical and laboratory data. For diagnosis of
      HPS we use these signs of the disease: presence of liver disease (cirrhosis in
      the case), abnormalities in gas exchange by arterial blood gases, and evidence of
      pulmonary vasodilations by the contrast echocardiography. RESULTS: The SA were
      found in 21/40 (52.5%) patients and hepatopulmonary syndrome in 9/40 (22.5%). The
      HPS was observed in 8/21 (38.1%) of patients with SA and 1/19 (5.3%) patients
      were without this sign (P<0.01). We found no statistically significant difference
      between the SA and the presence of HPS with sex or age. Patients with SA had a
      higher hypoxemia [PaO2 84.8 +/- 11.5 mmHg and 19.8 +/- 14.7 mmHg alveolar
      arterial gradient of oxygen (AAG)] than those without SA (PaO2 90.8 +/- 10.7 mmHg
      and 10.9 +/- 11.7 AAG mmHg) (P<0.05). CONCLUSION: Our findings show a correlation
      between the presence of SA and HPS, suggesting that the SA may be cutaneous
      markers of HPS.

PMID- 24322188
TI  - Nonalcoholic fatty liver disease in menopausal women.
AB  - CONTEXT: Nonalcoholic Fatty Liver Disease (NAFLD) is common in postmenopausal
      women. It is associated with metabolic syndrome. However, the influence of
      hormone replacement therapy in NAFLD development in these women needs to be
      investigated. This study aimed to describe the clinical characteristics of NAFLD
      in postmenopausal women, and the relationship between hormone replacement therapy
      and this disease. METHODS: From April 2009 to April 2011, 292 postmenopausal
      women from National Health System from Northeast of Brazil were selected, and 251
      were included in this study. Menopause was defined as the absence of menstruation
      for 12 consecutive months in otherwise healthy women. Criteria to NAFLD included:
      presence of steatosis on abdominal ultrasound; history of alcohol consumption
      less than 20 g/day and exclusion of other liver diseases. All women underwent a
      clinical evaluation. Standard univariate and multivariate analyses were performed
      to evaluate the results. RESULTS: The mean age was 56.5 +/- 6.7 years. Hormone
      replacement therapy was referred by 21.1% (53) women and 78.9% (198) was not.
      Prevalence of NAFLD was 37.1% (93/251) in postmenopausal women, 26,4% (14/53) in
      the group with hormone replacement therapy and 39,9% (79/198) without hormone
      replacement therapy. Gamma-glutamyl transpeptidase (P = 0.001), alanine
      transaminase (P<0.01), ferritin (P<0.001) and insulin resistance (homeostatic
      model assessment of insulin resistance >=3) (P<0.001) were higher in the group of
      women with NAFLD diagnosis who did not referred the use of hormone replacement
      therapy. Metabolic syndrome was also more frequent in women with NAFLD, who did
      not refer hormone replacement therapy. CONCLUSION: In conclusion this data
      suggests elevated prevalence of NAFLD in postmenopausal women; negative
      association of hormone replacement therapy and NAFLD.

PMID- 24322189
TI  - Changes in quality of life after short and long term follow-up of Roux-en-Y
      gastric bypass for morbid obesity.
AB  - CONTEXT: It is unclear whether health-related quality of life (HRQL) is sustained
      in a long-term follow-up of morbidly obese patients who underwent Roux-en-Y
      gastric bypass (RYGB). Objective This study aims to analyze the HRQL changes
      following RYGB in short and long-term follow-up. METHODS: We compared the health
      related quality of life among three separate patient groups, using the Medical
      Outcomes Study 36-Item Short-Form Health Survey (SF-36). Group A - 50
      preoperative morbidly obese patients; Group B - 50 RYGB patients 1-2 years post
      surgery; Group C - 50 RYGB patients more than 7 years post-surgery. RESULTS: The
      groups were similar for gender, age and body mass index before surgery. We
      observed that physical functioning, social function, emotional role functioning
      and mental health scales did not vary between the three groups. The physical role
      functioning scale was unchanged in the short-term and decreased compared to the
      preoperative scale in the long-term follow-up. Bodily pain improved after the
      operation but returned to the initial level after 7 years. The vitality and
      general health perceptions improved after the operation and maintained these
      results after 7 years compared with the preoperative perceptions. CONCLUSIONS:
      RYGB improved health-related quality of life in three SF-36 domains (bodily pain,
      general health perceptions and vitality) in the short-term and two SF-36 domains
      (general health perceptions and vitality) in the long-term.

PMID- 24322190
TI  - Venous insufficiency and thromboembolic disease in bariatric surgery patients.
AB  - CONTEXT: Morbid obesity is associated with various co-morbidities, including
      chronic venous insufficiency. Bariatric surgery is the only effective treatment
      for morbid obesity, but with potential risks and possible complications,
      including venous thromboembolism. OBJECTIVE: To determine the prevalence of
      clinical and ultrasonographic signs of chronic venous insufficiency in morbid
      obese patients in preparation for bariatric surgery and the incidence of post
      operative venous thromboembolic disease. METHODS: Patients on work-up for
      bariatric surgery of Centro Terapeutico Especializado em Figado (CETEFI) and Pro
      Gastro surgical teams of the Hospital Beneficencia Portuguesa de Sao Paulo were
      included. The analysed data were pre-operative findings for venous insufficiency
      (CEAP - clinical, etiological, anatomical, physiopathologic - classification and
      venous ultrasonographic findings), type of surgery (open or laparoscopic),
      abdominal circumference, body mass index (BMI) and post-operative ultrasonography
      search for venous insufficiency and deep venous thrombosis. RESULTS: Between
      March 2007 and December 2009, 95 patient candidates for bariatric surgery had
      clinical and duplex scan evaluation of the lower limbs venous system. Of the 95
      patients, 53 were submitted to the surgical procedure. There was a predominance
      of women (77.9%), the average age was 38.5 years, average preoperative weight
      124.6 kg and average BMI of 45.5 kg/m2. Regarding obesity, 16.8% were obese, and
      83.1% were morbidly obese. In relation to the venous findings, 86.3% of the
      patients did fit CEAP classification less than 3 and 13.7% greater than or equal
      to 3. Among the post-operative complications, there were four cases of wound
      infection. Three patients developed post-operative distal venous thrombosis
      (7.5%), but no one had clinically manifested pulmonary embolism. CONCLUSION: No
      relation between BMI, CEAP classification and venous ultrasonographic findings
      were found. Although prophylaxis was used in all patients, the incidence of post
      operative distal venous thrombosis was considerably high.

PMID- 24322191
TI  - Effect of the consumption of a cheese enriched with probiotic organisms
      (Bifidobacterium lactis bi-07) in improving symptoms of constipation.
AB  - CONTEXT: Constipation is a very common symptom in the general population. One way
      of non-pharmacological treatment of constipation is through the addition of
      probiotics to food. OBJECTIVES: The aim of this study was to evaluate de effect
      of the consumption of a fresh cheese, enriched with Bifidobacterium lactis Bi-07
      on the symptoms of constipated women. METHODS: A randomized controlled trial,
      carried out in the Basic Health Units of Guapore's City - RS/Brazil, between
      January and May 2012, with 30 constipated women. The patients were randomized
      into two groups whom received, for 30 days, 30 g of fresh cheese enriched with
      Bifidobacterium lactis Bi-07 (n = 15) or regular fresh cheese (n = 15).
      Constipation symptoms were evaluated according to ROMA III Consensus, before and
      after the nutritional intervention. Also, data of clinical and anthropometric
      characteristics of the individuals were collected. Accepted level of significance
      5% (P<=0,05). RESULTS: The medium age of the studied population was 37,5+/-14,4
      years in the intervention group and 40,8+/-12,8 years in the control group. After
      30 days we observed that the ingestion of fresh cheese enriched with
      Bifidobacterium lactis Bi-07 promoted benefic effects on the symptoms of strength
      to evacuate. CONCLUSION: The consumption of 30g/day of a fresh cheese enriched
      with Bifidobacterium lactis Bi-07 has beneficial effects on constipation
      symptoms.

PMID- 24322192
TI  - Acupuncture effectiveness as a complementary therapy in functional dyspepsia
      patients.
AB  - CONTEXT: Functional dyspepsia represents a frequent gastrointestinal disorder in
      clinical practice. According to the Roma III criteria, functional dyspepsia can
      be classified into two types as the predominant symptom: epigastric pain and
      postprandial discomfort. Even though the pathophysiology is still uncertain, the
      functional dyspepsia seems to be related to multiple mechanisms, among them
      visceral hypersensitivity, changes in the gastroduodenal motility and gastric
      accommodation and psychological factors. OBJECTIVE: Evaluate the effectiveness of
      acupuncture as a complementary to conventional treatment in functional dyspepsia
      patients. METHODS: Randomized clinical trial in which were enrolled patients with
      functional dyspepsia patients in according with Rome III criteria. One group was
      submitted to drug therapy and specific acupuncture (GI) and the other to drug
      therapy and non-specific acupuncture (GII). The gastrointestinal symptoms,
      presence of psychiatric disorders and quality of life were evaluated, at the end
      and three months after treatment. RESULTS: After 4 weeks of treatment there was
      improvement of gastrointestinal symptoms in Group I (55 +/- 12 vs 29 +/- 8.8; P =
      0.001) and Group II (50.5 +/- 10.2 vs 46 +/- 10.5; P = 0.001). Quality of life
      was significantly better in Group I than group II (93.4 +/- 7.3 vs 102.4 +/- 5.1;
      P = 0.001). Anxiety (93.3% vs 0%; P = 0.001) and depression (46.7% vs 0%; P =
      0.004) were significantly lower in Group I than group II. When comparing the two
      groups after 4 weeks of treatment, gastrointestinal symptoms (29 +/- 8.8 vs 46 +/
      10.5; P<0.001) and quality of life (102.4 +/- 5.1 vs 96 +/- 6.1; P = 0.021) were
      significantly better in Group I than group II. Three months after the treatment,
      gastrointestinal symptoms remained better only in Group I, when compared to the
      pre-treatment values (38 +/- 11.3 vs 55 +/- 12; P = 0.001). CONCLUSION: In
      patients with functional dyspepsia the complementary acupuncture treatment is
      superior to conventional treatment. Further studies with more patients are needed
      to confirm these findings.

PMID- 24322193
TI  - Lung and liver changes due to the induction of cirrhosis in two experimental
      models.
AB  - CONTEXT: To evaluate lung and liver changes in two experimental models using
      intraperitoneal carbon tetrachloride (CCl4) and bile duct ligation (BDL).
      methods: Twenty-four male Wistar rats were divided into a control group (CO) and
      an experimental group (EX). We evaluated the liver transaminases (AST, ALT, AP),
      arterial blood gases (PaO2, PCO2 and SpO2) and lipid peroxidation by TBARS
      (substances that react to thiobarbituric acid) and chemiluminescence. We also
      evaluated the antioxidant enzyme superoxide dismutase (SOD) and histology of lung
      tissue and liver. RESULTS: There were significant differences in AST, ALT, ALP
      and PaO2 between CO group and EX group (P<0.05). The levels of TBARS,
      chemiluminescence and activity of enzyme superoxide dismutase were increased to
      different degrees in the CCl4 groups: CO and in the BDL -EX (P<0.05,
      respectively). In the lung histology, an increase in the wall thickness of the
      pulmonary artery and a diameter reduction in the CCl4 animal model were observed:
      comparing CO group with EX group, we observed a reduction in thickness and an
      increase in the diameter of the artery wall lung. CONCLUSION: Both experimental
      models have caused liver damage and alterations in the artery wall that are
      associated with major changes in pulmonary gas exchange.

PMID- 24322194
TI  - Laparoscopic pancreatic resection. From enucleation to pancreatoduodenectomy. 11
      year experience.
AB  - CONTEXT: Our experience with laparoscopic pancreatic resection began in 2001.
      During initial experience, laparoscopy was reserved for selected cases. With
      increasing experience more complex laparoscopic procedures such as central
      pancreatectomy and pancreatoduodenectomies were performed. OBJECTIVES: The aim of
      this paper is to review our personal experience with laparoscopic pancreatic
      resection over 11-year period. METHODS: All patients who underwent laparoscopic
      pancreatic resection from 2001 through 2012 were reviewed. Preoperative data
      included age, gender, and indication for surgery. Intraoperative variables
      included operative time, bleeding, blood transfusion. Diagnosis, tumor size,
      margin status were determined from final pathology reports. RESULTS: Since 2001,
      96 patients underwent laparoscopic pancreatectomy. Median age was 55 years old.
      60 patients were female and 36 male. Of these, 88 (91.6%) were performed totally
      laparoscopic; 4 (4.2%) needed hand-assistance, 1 robotic assistance. Three
      patients were converted. Four patients needed blood transfusion. Operative time
      varied according type of operation. Mortality was nil but morbidity was high,
      mainly due to pancreatic fistula (28.1%). Sixty-one patients underwent distal
      pancreatectomy, 18 underwent pancreatic enucleation, 7 pylorus-preserving
      pancreatoduodenectomies, 5 uncinate process resection, 3 central and 2 total
      pancreatectomies. CONCLUSIONS: Laparoscopic resection of the pancreas is a
      reality. Pancreas sparing techniques, such as enucleation, resection of uncinate
      process and central pancreatectomy, should be used to avoid exocrine and/or
      endocrine insufficiency that could be detrimental to the patient's quality of
      life. Laparoscopic pancreatoduodenectomy is a safe operation but should be
      performed in specialized centers by highly skilled laparoscopic surgeons.

PMID- 24322195
TI  - Melting curve analysis for the screening of hepatitis B virus genotypes A, D and
      F in patients from a general hospital in southern Brazil.
AB  - CONTEXT: Hepatitis B virus (HBV) can cause fulminant hepatitis, cirrhosis and
      hepatocellular carcinoma, and is one of the most common causes of acute and
      chronic liver failure. The genetic variants of HBV can be decisive for the
      evolution of these diseases as well as for the election of therapy. OBJECTIVES:
      The aim of this study was to evaluate and standardize an in house methodology
      based on the analysis of the melting curve polymerase chain reaction (PCR) of
      real-time (qPCR) to screen for genotypes A, D and F of HBV in patients from a
      hospital in Rio Grande do Sul, Brazil. METHODS: We evaluated 104 patients
      presumably with HBV chronic infection. Viral DNA was extracted from plasma and
      viral genotypes and different mutations were determined using PCR-based
      protocols. RESULTS: A PCR-based methodology was standardized for the analysis of
      genotypes A, D and F of HBV. The technique was based in a nested PCR with the
      final step consisting of a multiplex real-time PCR, using the melting curve as a
      tool for the differentiation of fragments. A higher frequency of genotype D
      (44.4%), followed by genotype A (22.2%) and genotype F (3.7%) was observed.
      CONCLUSION: The standardized assay, a nested PCR-multiplex qPCR using specific
      primers, provides a rapid and accurate method for the differentiation of HBV
      genotypes that are more frequent in Southern Brazil - A, D and F. This method can
      be applied in the clinical practice.

PMID- 24322196
TI  - Fructose malabsorption in children with functional digestive disorders.
AB  - CONTEXT: Fructose is a monosaccharide frequently present in natural and
      artificial juice fruits. When the concentration of fructose in certain food is
      present in excess of glucose concentration some individuals may develop fructose
      malabsorption. OBJECTIVES: To report the frequency of fructose malabsorption
      utilizing the hydrogen breath test in children with gastrointestinal and/or
      nutritional disorders. METHODS: Between July 2011 and July 2012, 43 patients with
      gastrointestinal and/or nutritional disorders, from both sexes, were
      consecutively studied, utilizing the hydrogen breath test with loads of the
      following carbohydrates: lactose, glucose, fructose and lactulose. Fructose was
      offered in a 10% aqueous solution in the dose of 1 g/kg body weight. Samples were
      collected fasting and at every 15 minutes after the intake of the aqueous
      solution for a 2 hour period. Malabsorption was considered when there was an
      increase of >20 ppm of hydrogen over the fasting level, and intolerance was
      diagnosed if gastrointestinal symptoms would appear. RESULTS: The age of the
      patients varied from 3 months to 16 years, 24 were boys. The following diagnosis
      were established: irritable bowel syndrome with diarrhea in 16, functional
      abdominal pain in 8, short stature in 10, lactose intolerance in 3, celiac
      disease in 1, food allergy in 1 and giardiasis in 1 patient. Fructose
      malabsorption was characterized in 13 (30.2%) patients, and intolerance in 1
      (2.3%) patient. The most frequent fructose malabsorption was characterized in 7
      (16.3%) patients with irritable bowel syndrome and in 4 (9.3%) patients with
      functional abdominal pain. CONCLUSIONS: Patients with irritable bowel syndrome
      and functional abdominal pain were the main cause of fructose malabsorption.

PMID- 24322197
TI  - Dermatitis herpetiformis, the celiac disease of the skin!

PMID- 24322198
TI  - Perioperative chemotherapy in locally advanced gastric cancer.
AB  - Gastric cancer is one of the most common cancers and a main cause of cancer
      related death worldwide, since the majority of patients suffering of this
      malignancy are usually faced with a poor prognosis due to diagnosis at later
      stages. In order to improve treatment outcomes, the association of surgery with
      chemo and/or radiotherapy (multimodal therapy) has become the standard treatment
      for locally advanced stages. However, despite several treatment options currently
      available for management of these tumors, perioperative chemotherapy has been
      mainly accepted for the comprehensive therapeutic strategy including an
      appropriated D2-gastrectomy. This manuscript presents a (nonsystematic) critical
      review about the use of perioperative chemotherapy, with a special focus on the
      drugs delivery. 

PMID- 24322200
TI  - White light upconversion in Yb-sensitized (Tm, Ho)-doped KLu(WO4)2 nanocrystals:
      the effect of Eu incorporation.
AB  - Monoclinic Yb-sensitized (Tm, Ho)-doped KLu(WO4)2 nanocrystals of ~100 nm size
      have been synthesized by the modified Pechini sol-gel method. Their diode laser
      near-infrared (~980 nm) excited upconversion emission properties have been
      characterized at power densities in the range 30-355 W cm(-2). Bright white light
      composed of blue ~475 nm, green ~540 nm, and red ~650 nm emissions, corresponding
      to Tm(3+ 1)G4 -> (3)H6, Ho(3+ 5)S2, (5)F4 -> (5)I8, and Ho(3+ 5)F5 -> (5)I8
      electronic transitions, respectively, was generated by adjusting the Yb, Tm, and
      Ho contents in KLu(WO4)2 nanocrystalline samples. Chromaticity coordinates of the
      emitted white light can be tuned by modifying the excitation power density. The
      effect of Tm and Ho on the luminescence dynamics has been described by analyzing
      the upconverted emission intensity dependence on the excitation power, as well as
      from Stokes and decay time measurements. The effect on upconversion properties of
      further codoping with Eu in these (Tm, Ho, Yb)-doped KLu(WO4)2 nanocrystals has
      also been studied.

PMID- 24322199
TI  - Retinal vascular caliber and the development of hypertension: a meta-analysis of
      individual participant data.
AB  - OBJECTIVE: Microvascular dysfunction has been suggested to be a major pathogenic
      factor for the development of hypertension. We examined the association between
      retinal vascular caliber, a marker of systemic microvascular dysfunction, and
      incident hypertension on a meta-analysis of individual participant data. METHODS:
      We performed a systematic review with relevant studies identified through a
      search of electronic databases, a review of reference lists, and correspondence
      with experts. Studies were included if participants were selected from a general
      population, retinal vascular caliber was measured from photographs using computer
      assisted methods at baseline, and individuals were followed up to ascertain the
      incidence of hypertension. Prespecified individual recorded data from six
      population-based prospective cohort studies were included. Discrete time
      proportional odds models were constructed for each study with adjustment for
      hypertension risk factors. Log odds ratios (ORs) per 20-MUm difference were
      pooled using random-effects meta-analysis. RESULTS: Among 10 229 participants
      without prevalent hypertension, diabetes, or cardiovascular disease, 2599
      developed new-onset hypertension during median follow-up periods ranging from 2.9
      to 10 years. Both narrower retinal arterioles [pooled multivariate-adjusted OR
      per 20-MUm difference 1.29, 95% confidence interval (CI) 1.20-1.39] and wider
      venules (OR per 20-MUm difference 1.14, 95% CI 1.06-1.23) were associated with an
      increased risk of hypertension. Each 20 MUm narrower arterioles at baseline were
      associated with a 1.12 mmHg (95% CI 0.25-1.99) greater increase in SBP over 5
      years. CONCLUSIONS: Retinal arteriolar narrowing and venular widening were
      independently associated with an increased risk of hypertension. These findings
      underscore the importance of microvascular remodeling in the pathogenesis of
      hypertension.

PMID- 24322202
TI  - Exploitation of the Streptomyces coelicolor A3(2) genome sequence for discovery
      of new natural products and biosynthetic pathways.
AB  - Streptomyces, and related genera of Actinobacteria, are renowned for their
      ability to produce antibiotics and other bioactive natural products with a wide
      range of applications in medicine and agriculture. Streptomyces coelicolor A3(2)
      is a model organism that has been used for more than five decades to study the
      genetic and biochemical basis for the production of bioactive metabolites. In
      2002, the complete genome sequence of S. coelicolor was published. This greatly
      accelerated progress in understanding the biosynthesis of metabolites known or
      suspected to be produced by S. coelicolor and revealed that streptomycetes have
      far greater potential to produce bioactive natural products than suggested by
      classical bioassay-guided isolation studies. In this article, efforts to exploit
      the S. coelicolor genome sequence for the discovery of novel natural products and
      biosynthetic pathways are summarized. 

PMID- 24322203
TI  - In vivo evidence for greater amphetamine-induced dopamine release in pathological
      gambling: a positron emission tomography study with [(11)C]-(+)-PHNO.
AB  - Drug addiction has been associated with deficits in mesostriatal dopamine (DA)
      function, but whether this state extends to behavioral addictions such as
      pathological gambling (PG) is unclear. Here we used positron emission tomography
      and the D3 receptor-preferring radioligand [(11)C]-(+)-PHNO during a dual-scan
      protocol to investigate DA release in response to oral amphetamine in
      pathological gamblers (n=12) and healthy controls (n=11). In contrast with human
      neuroimaging findings in drug addiction, we report the first evidence that PG is
      associated with greater DA release in dorsal striatum (54-63% greater [(11)C]-(+)
      PHNO displacement) than controls. Importantly, dopaminergic response to
      amphetamine in gamblers was positively predicted by D3 receptor levels (measured
      in substantia nigra), and related to gambling severity, allowing for construction
      of a mechanistic model that could help explain DA contributions to PG. Our
      results are consistent with a hyperdopaminergic state in PG, and support the
      hypothesis that dopaminergic sensitization involving D3-related mechanisms might
      contribute to the pathophysiology of behavioral addictions. 

PMID- 24322204
TI  - Genome-wide association study of bipolar disorder accounting for effect of body
      mass index identifies a new risk allele in TCF7L2.
AB  - Bipolar disorder (BD) is associated with higher body mass index (BMI) and
      increased metabolic comorbidity. Considering the associated phenotypic traits in
      genetic studies of complex diseases, either by adjusting for covariates or by
      investigating interactions between genetic variants and covariates, may help to
      uncover the missing heritability. However, obesity-related traits have not been
      incorporated in prior genome-wide analyses of BD as covariates or potential
      interacting factors. To investigate the genetic factors underlying BD while
      considering BMI, we conducted genome-wide analyses using data from the Genetic
      Association Information Network BD study. We analyzed 729,454 genotyped single
      nucleotide polymorphism (SNP) markers on 388 European-American BD cases and 1020
      healthy controls with available data for maximum BMI. We performed genome-wide
      association analyses of the genetic effects while accounting for the effect of
      maximum BMI, and also evaluated SNP-BMI interactions. A joint test of main and
      interaction effects demonstrated significant evidence of association at the
      genome-wide level with rs12772424 in an intron of TCF7L2 (P=2.85E-8). This SNP
      exhibited interaction effects, indicating that the bipolar susceptibility risk of
      this SNP is dependent on BMI. TCF7L2 codes for the transcription factor TCF/LF,
      part of the Wnt canonical pathway, and is one of the strongest genetic risk
      variants for type 2 diabetes (T2D). This is consistent with BD pathophysiology,
      as the Wnt pathway has crucial implications in neurodevelopment, neurogenesis and
      neuroplasticity, and is involved in the mechanisms of action of BD and depression
      treatments. We hypothesize that genetic risk for BD is BMI dependent, possibly
      related to common genetic risk with T2D.

PMID- 24322205
TI  - Modulation of behavioral networks by selective interneuronal inactivation.
AB  - Gamma-aminobutyric acid (GABA)-ergic disturbances are hallmark features of
      schizophrenia and other neuropsychiatric disorders and encompass multiple
      interneuronal cell types. Using bacterial artificial chromosome-driven, miRNA
      silencing technology we generated transgenic mouse lines that suppress glutamic
      acid decarboxylase 1 (GAD1) in either cholecystokinin (CCK)- or neuropeptide Y
      (NPY)-expressing interneurons. In situ lipidomic and proteomic analyses on brain
      tissue sections revealed distinct, brain region-specific profiles in each
      transgenic line. Behavioral analyses revealed that suppression of GAD1 in CCK+
      interneurons resulted in locomotor and olfactory sensory changes, whereas
      suppression in NPY+ interneurons affected anxiety-related behaviors and social
      interaction. Both transgenic mouse lines had altered sensitivity to amphetamine
      albeit in opposite directions. Together, these data argue that reduced GAD1
      expression leads to altered molecular and behavioral profiles in a cell type
      dependent manner, and that these subpopulations of interneurons are strong and
      opposing modulators of dopamine system function. Furthermore, our findings also
      support the hypothesis that neuronal networks are differentially controlled by
      diverse inhibitory subnetworks.

PMID- 24322207
TI  - Eutectics as improved pharmaceutical materials: design, properties and
      characterization.
AB  - Eutectics are a long known class of multi-component solids with important and
      useful applications in daily life. In comparison to other multi-component
      crystalline solids, such as salts, solid solutions, molecular complexes and
      cocrystals, eutectics are less studied in terms of molecular structure
      organization and bonding interactions. Classically, a eutectic is defined based
      on its low melting point compared to the individual components. In this article,
      we attempt to define eutectics not just based on thermal methods but from a
      structural organization view point, and discuss their microstructures and
      properties as organic materials vis-a-vis solid solutions and cocrystals. The X
      ray crystal structure of a cocrystal is different from that of the individual
      components whereas the unit cell of a solid solution is similar to that of one of
      the components. Eutectics are closer to the latter species in that their
      crystalline arrangement is similar to the parent components but they are
      different with respect to the structural integrity. A solid solution possesses
      structural homogeneity throughout the structure (single phase) but a eutectic is
      a heterogeneous ensemble of individual components whose crystal structures are
      like discontinuous solid solutions (phase separated). Thus, a eutectic may be
      better defined as a conglomerate of solid solutions. A structural analysis of
      cocrystals, solid solutions and eutectics has led to an understanding that
      materials with strong adhesive (hetero) interactions between the unlike
      components will lead to cocrystals whereas those having stronger cohesive
      (homo/self) interactions will more often give rise to solid solutions (for
      similar structures of components) and eutectics (for different structures of
      components). We demonstrate that the same crystal engineering principles which
      have been profitably utilized for cocrystal design in the past decade can now be
      applied to make eutectics as novel composite materials, illustrated by stable
      eutectics of the hygroscopic salt of the anti-tuberculosis drug ethambutol as a
      case study. A current gap in the characterization of eutectic microstructure may
      be fulfilled through pair distribution function (PDF) analysis of X-ray
      diffraction data, which could be a rapid signature technique to differentiate
      eutectics from their components. 

PMID- 24322208
TI  - Totally endoscopic robotic coronary artery bypass surgery.
AB  - PURPOSE OF REVIEW: To assess the current status and methods of robotic totally
      endoscopic coronary artery bypass (TECAB) surgery and discuss important
      anesthetic considerations. RECENT FINDINGS: Technological and surgical advances
      in robotics have led to the evolution of TECAB surgery from a single-vessel
      procedure to quadruple-vessel bypass. TECAB is now a reproducible technique, with
      a low incidence of mortality and morbidity and superior quality of life. Although
      early cohorts of patients are still being observed for long-term outcomes,
      initial and midterm outcomes are comparable to those of conventional coronary
      artery bypass. TECAB is also associated with specific challenges for the
      anesthesiologist. SUMMARY: TECAB surgery is a feasible alternative to open
      coronary artery bypass surgery in selected patient populations. Appropriate
      patient selection, team training, and stepwise application of the procedure are
      crucial. TECAB is associated with a unique set of challenges, requiring a skilled
      operative team. As robotic technology and surgical expertise evolve, this
      technology will find wider application in an increasing high-risk patient
      population that will require the support of a skilled anesthesiology team.

PMID- 24322206
TI  - Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia
      and affective disorders, and associations with SNPs in postmortem brain.
AB  - Dopamine 2 receptor (DRD2) is of major interest to the pathophysiology of
      schizophrenia (SCZ) both as a target for antipsychotic drug action as well as a
      SCZ-associated risk gene. The dopamine 1 receptor (DRD1) is thought to mediate
      some of the cognitive deficits in SCZ, including impairment of working memory
      that relies on normal dorsolateral prefrontal cortex (DLPFC) function. To better
      understand the association of dopamine receptors with SCZ, we studied the
      expression of three DRD2 splice variants and the DRD1 transcript in DLPFC,
      hippocampus and caudate nucleus in a large cohort of subjects (~700), including
      patients with SCZ, affective disorders and nonpsychiatric controls (from 14th
      gestational week to 85 years of age), and examined genotype-expression
      associations of 278 single-nucleotide polymorphisms (SNPs) located in or near
      DRD2 and DRD1 genes. Expression of D2S mRNA and D2S/D2-long (D2L) ratio were
      significantly increased in DLPFC of patients with SCZ relative to controls
      (P<0.0001 and P<0.0001, respectively), whereas D2L, D2Longer and DRD1 were
      decreased (P<0.0001). Patients with affective disorders showed an opposite
      pattern: reduced expression of D2S (major depressive disorder, P<0.0001) and
      increased expression of D2L and DRD1 (bipolar disorder, P<0.0001). Moreover, SCZ
      associated risk alleles at rs1079727, rs1076560 and rs2283265 predicted increased
      D2S/D2L expression ratio (P<0.05) in control individuals. Our data suggest that
      altered splicing of DRD2 and expression of DRD1 may constitute a
      pathophysiological mechanism in risk for SCZ and affective disorders. The
      association between SCZ risk-associated polymorphism and the ratio of D2S/D2L is
      consistent with this possibility. 

PMID- 24322209
TI  - Novel approaches to spinal cord protection during thoracoabdominal aortic
      interventions.
AB  - PURPOSE OF REVIEW: Spinal cord ischemia after thoracoabdominal aortic
      interventions is a devastating complication because it significantly worsens the
      perioperative morbidity and mortality. Long-term outcome is also affected because
      of medical complications which are directly related to the neural deficits.
      Paraplegia has significant medical, social, and financial aspects. Limited
      mobility, the need for assistance in activities of daily living, makes paraplegia
      an important target for prevention. An understanding of spinal cord blood supply,
      risk factors for spinal ischemia, and strategies for spinal cord rescue in this
      setting can help minimize the negative outcome effects of this important
      complication. RECENT FINDINGS: The vascular supply of the spinal cord is via an
      extensive collateral arterial network with multiple auxiliary arterial supplies.
      Risk factors for spinal cord ischemia include extensive aortic repair, prior
      aortic repair, spinal cord malperfusion on clinical presentation, systemic
      hypotension, acute anemia, prolonged aortic clamping, and vascular steal. Spinal
      rescue strategies include systemic hypothermia, endovascular aortic repair,
      permissive systemic hypertension, cerebrospinal fluid drainage, pharmacologic
      neuroprotection, and intensive neuromonitoring. SUMMARY: The progression of
      spinal cord ischemia after thoracoabdominal aortic interventions can frequently
      be arrested before irreversible infarction results. This spinal cord rescue
      depends on the early detection and immediate multimodal intervention to maximize
      spinal cord oxygen supply. The devastating outcomes associated with spinal
      infarction in this setting offset the risks and knowledge gaps currently
      associated with contemporary interventions.

PMID- 24322210
TI  - Pain and inflammatory response following off-pump coronary artery bypass
      grafting.
AB  - PURPOSE OF REVIEW: Inflammation and pain are two common clinical issues following
      cardiac surgery, which are important to patient outcomes. This article reviews
      the literature regarding inflammation and pain following cardiac surgery with
      special emphasis on off-pump cardiac surgery. RECENT FINDINGS: Off-pump surgery
      is associated with decreased intraoperative inflammatory response compared with
      procedures using cardiopulmonary bypass; however, the postoperative pattern of
      inflammatory response is similar to on-pump procedures. Multimodal analgesic
      regimens and protocol-based approaches to pain management improve analgesia
      compared to conventional approaches. SUMMARY: Off-pump cardiac surgeries although
      known to decrease the inflammatory burden do not appear to impact the overall
      patient outcomes. Recent evidence indicates the prothrombotic tendency following
      off-pump procedures, which could be related to the time course of inflammation
      following off-pump cardiac surgery. There might be some benefit of off-pump
      procedures regarding neurological and renal function that needs further studies.
      Pain management following off-pump procedures is similar to that of patients
      undergoing on-pump cardiac surgery. Better caregiver and patient education is
      crucial for improving pain control following cardiac surgery. Analgesic regimens
      need to consider adjuvants and regional analgesic techniques and patient
      controlled modalities while providing care.

PMID- 24322211
TI  - Bronchoscopic treatment of end-stage chronic obstructive pulmonary disease.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a progressive,
      debilitating disease that in its final stages cripples the patient. The
      disappointing results of the National Emphysema Treatment Trial study led to a
      decrease in the acceptance of lung volume reduction surgery as a therapy. Thus,
      it became clear that debilitated COPD patients would need innovative alternative
      nonsurgical procedures to potentially alleviate their symptoms. This review will
      address the various techniques of bronchoscopic lung volume reduction (BLVR).
      RECENT FINDINGS: In recent years, a variety of noninvasive BLVR procedures were
      developed in the hope of improving the respiratory status of these patients. BLVR
      aims to decrease the extent of hyperinflation due to emphysema and result in a
      beneficial effect similar to that from surgical resection. The most widely used
      BLVR devices are: endobronchial valves, foam sealant, metallic coils, airway
      bypass stents and vapor thermal ablation.In the USA, BLVR remains in the
      experimental phase. The treatment modalities should be individually tailored for
      each patient. Endobronchial valves are designed to exclude the most affected
      emphysematous regions from ventilation in order to induce lobar absorption
      atelectasis. Airway bypass stents target homogenous emphysema, whereas valves and
      thermal vapor ablation target heterogeneous emphysema. Biological sealants and
      endoscopic coil implants have been used in both homogenous and heterogeneous
      emphysema. SUMMARY: BLVR appears to be safer than surgery and presents an
      attractive alternative for the treatment of COPD patients. Unfortunately, the
      outcome data to date are inconclusive; the procedures remain experimental and any
      benefits unproven. However, the data that are emerging continue to appear
      promising.

PMID- 24322212
TI  - Preoperative diagnosis of the responsible level in CCM using CMAPs: comparison
      with SCEPs.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To elucidate the correlation
      between compound muscle action potentials (CMAPs) amplitudes and responsible
      level of compressive cervical myelopathy (CCM), and the accuracy of level
      diagnosis by using CMAPs. SETTING: This study was conducted at the Department of
      Orthopedic surgery, Yamaguchi University Graduate School of Medicine, Japan.
      METHOD: A total of 28 patients with CCM were investigated in this study. Erb's
      point-stimulated CMAPs were measured from deltoid, biceps, triceps in all
      patients as compared with 88 healthy subjects. We performed a level diagnosis on
      the basis of CMAPs amplitudes. We performed a level diagnosis on the basis of
      CMAPs amplitudes and using an index that measures the deviation of CMAPs
      amplitudes between triceps and deltoid or biceps. RESULTS: Significant
      correlations between the mean CMAPs amplitudes and responsible level were showed
      for deltoid (6.82+/-2.33 mV) at C3/4 (P<0.01) and biceps (8.75+/-4.42 mV) at C4/5
      (P=0.015). Despite considerable individual variability in CMAP amplitudes, there
      were correlations among CMAPs amplitudes for deltoid, biceps and triceps in the
      same individual. The sensitivity was 75.0%, specificity 75.0% in the index for
      diagnosis of C3/4. The sensitivity was 75.0%, specificity 66.7% in the index for
      diagnosis of C4/5. CONCLUSION: This study showed small CMAPs amplitudes in the
      deltoid indicated a C3/4 level of myelopathy and in biceps at the C4/5 level and
      could help exclude clinically silent cord compression and determine the surgical
      procedure to the suitable level of concern.

PMID- 24322213
TI  - Resilience, self-esteem and self-compassion in adults with spina bifida.
AB  - STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To examine factors that may
      enhance and promote resilience in adults with spina bifida. SETTING: Community
      based disability organisations within Australia. METHODS: Ninety-seven adults
      with a diagnosis of spina bifida (SB) completed a survey comprising of
      demographic questions in addition to standardised self-report measures of
      physical functioning (Craig Handicap Assessment and Reporting Technique),
      resilience (Connor-Davidson Resilience Scale, 10 item), self-esteem (Rosenberg
      Self-esteem Scale), self-compassion (Self-compassion Scale) and psychological
      distress (Depression Anxiety Stress Scales, 21 item). RESULTS: The majority (66%)
      of respondents reported moderate to high resilience. Physical disability impacted
      on coping, with greater CD-RISC 10 scores reported by individuals who were
      functionally independent in addition to those who experienced less medical co
      morbidities. Significant correlations between resilience and psychological traits
      (self-esteem r=0.36, P<0.01; self-compassion r=0.40, P<0.01) were also noted.
      However, the combined contribution of these variables only accounted for 23% of
      the total variance in resilience scores (R(2)=0.227, F(5,94)=5.23, P<0.01).
      CONCLUSION: These findings extend current understanding of the concept of
      resilience in adults with a congenital physical disability. The suggestion is
      that resilience involves a complex interplay between physical determinants of
      health and psychological characteristics, such as self-esteem and self
      compassion. It follows that cognitive behavioural strategies with a focus on self
      management may, in part, contribute to the process of resilience in this group.
      Further large-scale and longitudinal research will help to confirm these
      findings.

PMID- 24322214
TI  - Estimating the global incidence of traumatic spinal cord injury.
AB  - STUDY DESIGN: Population modelling--forecasting. OBJECTIVES: To estimate the
      global incidence of traumatic spinal cord injury (TSCI). SETTING: An initiative
      of the International Spinal Cord Society (ISCoS) Prevention Committee. METHODS:
      Regression techniques were used to derive regional and global estimates of TSCI
      incidence. Using the findings of 31 published studies, a regression model was
      fitted using a known number of TSCI cases as the dependent variable and the
      population at risk as the single independent variable. In the process of deriving
      TSCI incidence, an alternative TSCI model was specified in an attempt to arrive
      at an optimal way of estimating the global incidence of TSCI. RESULTS: The global
      incidence of TSCI was estimated to be 23 cases per 1,000,000 persons in 2007
      (179,312 cases per annum). World Health Organization's regional results are
      provided. DISCUSSION: Understanding the incidence of TSCI is important for health
      service planning and for the determination of injury prevention priorities. In
      the absence of high-quality epidemiological studies of TSCI in each country, the
      estimation of TSCI obtained through population modelling can be used to overcome
      known deficits in global spinal cord injury (SCI) data. The incidence of TSCI is
      context specific, and an alternative regression model demonstrated how TSCI
      incidence estimates could be improved with additional data. The results highlight
      the need for data standardisation and comprehensive reporting of national level
      TSCI data. A step-wise approach from the collation of conventional
      epidemiological data through to population modelling is suggested.

PMID- 24322215
TI  - Reliability and validity of the Turkish version of spinal cord lesion-related
      coping strategies.
AB  - OBJECTIVE: Spinal Cord Lesion-Related Coping Strategies Questionnaire (SCL CSQ)
      is a specific test that is developed for evaluating the coping strategies of the
      persons with spinal cord injury (SCI). The aim of this study was to evaluate the
      reliability and validity of the Turkish version of SCL CSQ (SCL CSQ-T) in persons
      with SCI. METHODS: One hundred persons with SCI were included in the study. All
      participants were evaluated with SCL CSQ-T and Brief Coping Styles Inventory
      (BCSI) at the baseline. SCL CSQ-T was repeated twice in 15 days. American Spinal
      Injury Association Impairment Scale and Functional Independence Measurement were
      used for the evaluation of the neurological loss severity and functional status.
      Emotional status was assessed by Hospital Anxiety and Depression Scale (HADS).
      Internal consistency reliability, test-retest reliability and construct validity
      of SCL CSQ-T were evaluated. RESULTS: Intraclass correlation coefficients of the
      SCL CSQ-T were between 0.51-0.86. Cronbach's alpha values and test-retest
      reliability of the acceptance, fighting spirit and social reliance subscales were
      good. Three factors were found in exploratory factor analysis. There was a
      positive correlation between the subscales of SCL CSQ-T. There was a
      statistically significant positive correlation between acceptance strategy of SCL
      CSQ-T and self-confidence and optimism of BCSI. The fighting spirit strategy
      positively correlated with self-confidence and optimistic strategies. The social
      reliance strategy positively correlated with helplessness and seeking social
      support. Coping strategies did not correlate with HADS. CONCLUSION: The results
      of this study revealed good internal consistency reliability, test-retest
      reliability and concurrent validity of the SCL CSQ-T factors acceptance and
      fighting spirit in relation to general coping strategies. The coping strategy
      social reliance needs revisions.

PMID- 24322216
TI  - The effect of arm position and bed adjustment on comfort and pressure under the
      shoulders in people with tetraplegia: a randomized cross-over study.
AB  - STUDY DESIGN: Randomized, within-in participant cross-over study. OBJECTIVE: The
      purpose of this study was to determine the effect on comfort and pressure of
      lying with the shoulders and bed in different positions for people with
      tetraplegia. SETTING: Rehabilitation hospital. METHODS: Twenty people with
      tetraplegia were tested lying supine with the shoulders and bed in seven
      different positions. The positions used a combination of three arm and two bed
      positions. Six of the positions reflected what is commonly recommended in acute
      spinal cord injury units including a crucifix-type position. The seventh position
      was selected by participants and reflected their preferred sleeping position.
      There were five outcomes: general comfort, shoulder comfort, participant choice
      of preferred position, peak pressure under the shoulders and areal pressure under
      the shoulders. Pressure was measured using a pressure mapping system and comfort
      using a visual analogue scale (VAS). RESULTS: The participants reported
      significantly higher (P<0.01) general comfort and shoulder comfort in their self
      selected position compared with all other positions. There was no statistical
      difference in peak pressure (P=0.15) or areal pressure (P=0.08) under the
      shoulders between the seven positions. Most participants indicated that they
      preferred to lie with their shoulders adducted and internally rotated and the
      hands either by their sides or on their stomachs. CONCLUSION: The position of the
      shoulders has little effect on pressure but a notable effect on comfort.
      Participants preferred to sleep with their arms beside their bodies, not with
      their arms in a crucifix position as commonly advocated.

PMID- 24322217
TI  - Sexual function and associated factors in Iranian patients with chronic low back
      pain.
AB  - STUDY DESIGN: Case-control study. OBJECTIVES: (i) To describe the prevalence of
      sexual dysfunction in chronic low back pain (CLBP) patients, (ii) to compare the
      range of sexual function outcomes between patients with CLBP and healthy controls
      and (iii) to investigate which factors are associated with sexual function within
      the cohort of individuals with CLBP. SETTING: Low back pain (LBP) clinic of
      Qazvin University of Medical Sciences, Qazvin, Iran. METHODS: A total of 702
      patients with CLBP and 888 healthy controls participated in the study. The Female
      Sexual Function Index (FSFI), International Index of Erectile Function (IIEF) and
      Premature Ejaculation Diagnostic Tool (PEDT) were used to evaluate sexual
      function. In addition, quality of life, anxiety, functional status and pain
      intensity were assessed in patients. Univariate and multiple linear regression
      analyses were performed for the identification of factors associated with sexual
      function. RESULTS: The prevalence of sexual problems in female patients with CLBP
      was 71.1% (n=177) while the corresponding figure for healthy women was 36.8%
      (n=161). Erectile dysfunction was present in 59.5% of male patients and in 24.5%
      of healthy males. Higher sexual function in both male and female patients with
      CLBP were being younger, lower duration of back pain, lower BMI, higher education
      level, being unemployed, physically active shorter sick leave, lower level of
      pain intensity, lower disability, higher family income, lower levels of
      depressive and anxiety symptoms, and higher psychical functioning and mental
      functioning. CONCLUSIONS: CLBP patients report considerably higher prevalences of
      sexual problems compared with healthy controls. Sex therapy and sexual management
      should be added to routine care and treatment of patients with CLBP.

PMID- 24322218
TI  - Phase retrieval with resolution enhancement by using structured illumination.
AB  - In this Letter, we present referenceless phase retrieval methods with resolution
      enhancement. Structured illuminations with different orientations and phase
      shifts are generated by a spatial light modulator and are used to illuminate the
      specimen. The generated diffraction patterns are recorded by a CCD camera, and
      the phase of the wavefront is reconstructed from these patterns. 

PMID- 24322219
TI  - Are the fluctuations in dynamic anterior surface aberrations of the human eye
      chaotic?
AB  - The purpose of the study is to measure chaos in dynamic anterior surface
      aberrations and examine how it varies between the eyes of an individual.
      Noninvasive tear breakup time and dynamic corneal surface aberrations were
      measured for two open-eye intervals of 15 s. The maximal Lyapunov exponent (MLE)
      was calculated to test the nature of the fluctuations of the dynamic anterior
      surface aberrations. The average MLE for total higher-order aberration (HOA) was
      found to be small (+0.0102+/-0.0072) MUm/s. No significant difference in MLE was
      found between the eyes for HOA (t-test; p=0.131). Data analysis was carried out
      for individual Zernike coefficients, including vertical prism as it gives a
      direct measure of the thickness of the tear film over time. The results show that
      the amount of chaos was small for each Zernike coefficient and not significantly
      correlated between the eyes.

PMID- 24322220
TI  - 2 GHz passively harmonic mode-locked fiber laser by a microfiber-based
      topological insulator saturable absorber.
AB  - We report on the generation of passive harmonic mode locking of a fiber laser
      using a microfiber-based topological insulator (TI) Bi(2)Te(3) saturable absorber
      (SA). The optical deposition method was employed to fabricate the microfiber
      based TISA. By virtue of the excellent nonlinear optical property of the proposed
      TISA, the fiber laser could operate at the pulse repetition rate of 2.04 GHz
      under a pump power of 126 mW, corresponding to the 418th harmonic of fundamental
      repetition frequency. The results demonstrate that the microfiber-based TI
      photonic device can operate as both the high nonlinear optical component and the
      SA in fiber lasers, and could also find other applications in the related fields
      of photonics.

PMID- 24322221
TI  - Fano resonances in metasurfaces made of linear trimers of plasmonic
      nanoparticles.
AB  - We investigate Fano resonances in planar two-dimensional periodic arrays of
      linear trimers of plasmonic nanoparticles that appear under plane wave incidence.
      The observed Fano resonances are associated to resonances belonging to the trimer
      (metamolecule) itself, where some are found to be strongly affected by the array
      periodicity. We observe that array-dependent resonances appearing for oblique
      incidence are resistant to losses, whereas narrow dipolar-like Fano resonances
      associated mainly to the metamolecule, which appear also under normal incidence,
      disappear when losses are too high. In particular, we prove the latter by
      theoretical (dipolar approximation) and full-wave simulations, in good agreement.
      We propose that the use of very low-loss plasmonic materials or the use of gain
      materials to mitigate plasmonic losses may lead to (high-quality factor) dipolar
      like Fano resonances under normal incidence, exhibiting a certain degree of
      fabrication defect tolerance, which might be employed to improve sensors, lasing,
      switching, and nonlinear devices, for example. 

PMID- 24322222
TI  - All-optical spectral linewidth reduction of lasers for coherent optical
      communication.
AB  - We propose and experimentally demonstrate an effective spectral linewidth
      suppression scheme for a commercial tunable laser source. By using a long-cavity,
      narrow-bandwidth stimulated Brillouin scattering filter and multifrequency
      selection mechanism simultaneously, a single-longitudinal-mode laser output with
      linewidth suppression from ~3 MHz to less than 20 kHz is successfully achieved in
      the whole C-band. Meanwhile, insertion loss of ~5 dB and a side-mode suppression
      ratio improvement of ~20 dB at a typical output wavelength of 1552.520 nm are
      obtained. The scheme is experimentally verified to be wavelength independent in
      the C-band and characterized with good performance of wavelength and power
      stability.

PMID- 24322223
TI  - Enhanced photoluminescence emission from anthracene-doped polyphenylsiloxane
      glass.
AB  - Anthracene-doped polyphenylsiloxane (PPS) glass containing silver nanoparticles
      (AgNPs) of appropriate size was synthesized in a form of solid thin films for
      modifying light emission characteristics. The photoluminescence (PL) emission
      from the anthracene molecules at ~2.95 eV was resonantly coupled to the localized
      surface plasmon (LSP) polariton modes that were induced by the excitation of ~30
      nm sized AgNPs. The increase in absorption of incident photons within a highly
      scattering medium, energy transfer from the localized excitons to the LSP modes,
      and the electrostatic Coulomb effects of the excitons in the presence of metal
      NPs all resulted in a significant enhancement of PL emission. The PL enhancement
      is dependent on the concentration of the anthracene molecules. The integrated PL
      intensity enhancement at the optimum concentration of anthracene molecules in the
      PPS glass with AgNPs is found to exceed 50.

PMID- 24322224
TI  - Absolute photoacoustic thermometry in deep tissue.
AB  - Photoacoustic thermography is a promising tool for temperature measurement in
      deep tissue. Here we propose an absolute temperature measurement method based on
      the dual temperature dependences of the Gruneisen parameter and the speed of
      sound in tissue. By taking ratiometric measurements at two adjacent temperatures,
      we can eliminate the factors that are temperature irrelevant but difficult to
      correct for in deep tissue. To validate our method, absolute temperatures of
      blood-filled tubes embedded ~9 mm deep in chicken tissue were measured in a
      biologically relevant range from 28 degrees C to 46 degrees C. The temperature
      measurement accuracy was ~0.6 degrees C. The results suggest that our method can
      be potentially used for absolute temperature monitoring in deep tissue during
      thermotherapy.

PMID- 24322225
TI  - One-way optical tunneling induced by nonreciprocal dispersion of Tamm states in
      magnetophotonic crystals.
AB  - We show that optical Tamm states (OTSs) with nonreciprocal dispersion can be
      formed at the boundary separating two different magnetophotonic crystals
      magnetized in the Voigt geometry. At the frequencies of the Tamm states, one-way
      optical tunneling can be achieved. The nonreciprocity features of OTSs originate
      from the simultaneous violation of reciprocity, time-reversal, and all related
      spatial symmetries in the system. Our predictions are confirmed by the
      nonreciprocal dispersion of interface modes, unidirectional transmission spectra,
      and field distributions for our system. Such theoretical results may provide a
      mechanism to create compact optical isolators. 

PMID- 24322226
TI  - Wide-field two-dimensional multifocal optical-resolution photoacoustic-computed
      microscopy.
AB  - Optical-resolution photoacoustic microscopy (OR-PAM) is an emerging technique
      that directly images optical absorption in tissue at high spatial resolution. To
      date, the majority of OR-PAM systems are based on single-focused optical
      excitation and ultrasonic detection, limiting the wide-field imaging speed. While
      1D multifocal OR-PAM (1D-MFOR-PAM) has been developed, the potential of microlens
      and transducer arrays has not been fully realized. Here we present the
      development of 2D multifocal optical-resolution photoacoustic-computed microscopy
      (2D-MFOR-PACM), using a 2D microlens array and a full-ring ultrasonic transducer
      array. The 10 mm*10 mm microlens array generates 1800 optical foci within the
      focal plane of the 512-element transducer array, and raster scanning the
      microlens array yields optical-resolution photoacoustic images. The system has
      improved the in-plane resolution of a full-ring transducer array from >=100 to 29
      MUm and achieved an imaging time of 36 s over a 10 mm*10 mm field of view. In
      comparison, the 1D-MFOR-PAM would take more than 4 min to image over the same
      field of view. The imaging capability of the system was demonstrated on phantoms
      and animals both ex vivo and in vivo.

PMID- 24322227
TI  - Reconfigurable orbital angular momentum and polarization manipulation of 100
      Gbit/s QPSK data channels.
AB  - We demonstrate reconfigurable orbital angular momentum (OAM) and polarization
      manipulation of OAM- and polarization-multiplexed 100 Gbit/s quadrature phase
      shift keying (QPSK) data channels. Each data channel's OAM value and its
      polarization state can be arbitrarily changed by taking advantage of the unique
      wavefront profile of OAM beams using liquid crystal on silicon-based spatial
      light modulators. The manipulation operation introduces a power penalty of <1 dB
      for 100 Gbit/s QPSK signals.

PMID- 24322228
TI  - Graphene-clad tapered fiber: effective nonlinearity and propagation losses.
AB  - We derive a pulse propagation equation for a graphene-clad optical fiber,
      treating the optical response of the graphene and nonlinearity of the dielectric
      fiber core as perturbations in asymptotic expansion of Maxwell equations. We
      analyze the effective nonlinear and attenuation coefficients due to the graphene
      layer. Based on the recent experimental measurements of the nonlinear graphene
      conductivity, we predict considerable enhancement of the effective nonlinearity
      for subwavelength fiber core diameters. 

PMID- 24322229
TI  - Ion migration assisted inscription of high refractive index contrast waveguides
      by femtosecond laser pulses in phosphate glass.
AB  - In this Letter, we report on the successful fabrication of low loss, high
      refractive index contrast waveguides via ion migration upon femtosecond laser
      writing in phosphate glass. Waveguides were produced in two different phosphate
      glass compositions with high and low La(2)O(3) content. In the La-rich glass, a
      large refractive index increase in the guiding region was observed due to the
      incoming migration of La accompanied by the out-diffusion of K. The much smaller
      refractive index change in the La-less glass is caused by rearrangements of the
      glass structure. These results confirm the feasibility of adapting the glass
      composition for enabling the laser writing of high refractive index contrast
      structures via spatially selective modification of the glass composition.

PMID- 24322230
TI  - Light-controlled perfect absorption of light.
AB  - We study coherent perfect absorption (CPA) of light in a Kerr nonlinear metal
      dielectric composite medium, illuminated from the opposite ends. Elementary
      symmetry considerations reveal that equality of the incident light intensities is
      a prerequisite to ensure CPA in both linear and nonlinear systems for specific
      system parameters. We also derive the sufficient conditions for having CPA. We
      further show that, while CPA in a linear system is insensitive to the incident
      power level, in a nonlinear system CPA can be achieved only for discrete
      intensities with interesting hysteretic responses. Our unified formulation of CPA
      and waveguiding identifies them as opposite scattering phenomena. We further
      investigate light-induced CPA in on-resonant and off-resonant systems. 

PMID- 24322231
TI  - Broadband all-optical microwave photonics phase detector.
AB  - A microwave photonics phase detector is conceived and practically demonstrated.
      The phase-detector system employs a semiconductor optical amplifier as a four
      wave mixer to enable phase detection over a broad frequency range. The system
      behavior is first mathematically modeled and then demonstrated practically. Phase
      measurement over a frequency range of 1-18 GHz is achieved. This phase detector
      is an excellent candidate for wideband applications such as frequency-agile
      radar.

PMID- 24322232
TI  - Nonlinear frequency conversion in a birefringent microstructured fiber tuned by
      externally applied hydrostatic pressure.
AB  - We studied vector frequency conversion in externally tuned microstructured fibers
      for applications as a novel, nonlinear fiber-optic sensor. We investigated both
      experimentally and numerically a possibility of shifting vector and scalar
      modulation instability gain bands by pressure-induced changes in the linear
      properties of a microstructured fiber. Our results show that polarization
      dependent vector nonlinear processes sensitive to variation of fiber group
      velocity difference (group birefringence) exhibit a clear advantage for pressure
      sensing applications compared with scalar nonlinear processes only sensitive to
      group velocity dispersion changes. Analytical predictions and numerical
      simulations confirm our measurement results. 

PMID- 24322233
TI  - In-line FINCH super resolution digital holographic fluorescence microscopy using
      a high efficiency transmission liquid crystal GRIN lens.
AB  - We report a new optical arrangement that creates high-efficiency, high-quality
      Fresnel incoherent correlation holography (FINCH) holograms using polarization
      sensitive transmission liquid crystal gradient index (TLCGRIN) diffractive
      lenses. In contrast, current universal practice in the field employs a reflective
      spatial light modulator (SLM) to separate sample and reference beams.
      Polarization sensitive TLCGRIN lenses enable a straight optical path, have >90%
      transmission efficiency, are not pixilated, and are free of many limitations of
      reflective SLM devices. For each sample point, two spherical beams created by a
      glass lens in combination with a polarization sensitive TLCGRIN lens interfere
      and create a hologram and resultant super resolution image. 

PMID- 24322234
TI  - Cryogenic measurements of mechanical loss of high-reflectivity coating and
      estimation of thermal noise.
AB  - We report on low-frequency measurements of the mechanical loss of a high-quality
      (transmissivity T<5 ppm at lambda(0)=1064 nm, absorption loss <0.5 ppm)
      multilayer dielectric coating of ion-beam-sputtered fused silica and titanium
      doped tantala in the 10-300 K temperature range. A useful parameter for the
      computation of coating thermal noise on different substrates is derived as a
      function of temperature and frequency.

PMID- 24322235
TI  - Experimental validation of optimum input polarization states for Mueller matrix
      determination with a dual photoelastic modulator polarimeter.
AB  - Dual photoelastic modulator polarimeters can measure light polarization, which is
      often described as a Stokes vector. By evaluating changes in polarization when
      light interacts with a sample, the sample Mueller matrix also can be derived,
      completely describing its interaction with polarized light. The choice of which
      and how many input Stokes vectors to use for sample investigation is under the
      experimenter's control. Previous work has predicted that sets of input Stokes
      vectors forming the vertices of platonic solids on the Poincare sphere allow for
      the most robust Mueller matrix determination. Further, when errors specific to
      the dual photoelastic modulator polarimeter are considered, simulations revealed
      that one specific shape and orientation of Stokes vectors (cube on the Poincare
      sphere with vertices away from principal sphere axes) allows for the most robust
      Mueller matrix determination. Here we experimentally validate the optimum input
      Stokes vectors for dual photoelastic modulator Mueller polarimetry, toward
      developing a robust polarimetric platform of increasing relevance to
      biophotonics. 

PMID- 24322236
TI  - Purely nonlinear disorder-induced localizations and their parametric
      amplification.
AB  - We investigate spatial localization in a quadratic nonlinear medium in the
      presence of randomness. By means of numerical simulations and theoretical
      analyses we show that, in the down conversion regime, the transverse random
      modulation of the nonlinear susceptibility generates localizations of the
      fundamental wave that grow exponentially in propagation. The localization length
      is optically controlled by the pump intensity that determines the amplification
      rate. The results also apply to cubic nonlinearities. 

PMID- 24322238
TI  - Steering and guiding light with light in a nanosuspension.
AB  - We experimentally demonstrate guiding of a low-power probe beam (633 nm
      wavelength) by means of a light-induced waveguide generated by the self-focusing
      of a strong pump beam (532 nm wavelength) in an artificial nonlinear medium,
      constituted by a colloidal suspension of dielectric nanoparticles. We also
      demonstrate optical steering of the probe beam by controlling the direction of
      propagation of the pump beam. The distance over which guiding is demonstrated (5
      mm) is remarkably long when compared with previous experiments.

PMID- 24322237
TI  - Comparison of line-scanned and point-scanned dual-axis confocal microscope
      performance.
AB  - The point-scanned dual-axis confocal (PS-DAC) microscope has been shown to
      exhibit superior capability to reject out-of-focus and multiply scattered light
      in comparison to its conventional single-axis counterpart. However, the slow
      frame rate (typically <5 Hz) resulting from point-by-point data collection makes
      these systems vulnerable to motion artifacts. While video-rate point-scanned
      confocal microscopy is possible, a line-scanned dual-axis confocal (LS-DAC)
      microscope provides a simpler means of achieving high-speed imaging through line
      by-line data collection, but sacrifices contrast due to loss of confocality along
      one dimension. Here we evaluate the performance trade-offs between an LS-DAC and
      PS-DAC microscope with identical spatial resolutions. Characterization
      experiments of the LS-DAC and PS-DAC microscopes with tissue phantoms, in
      reflectance mode, are shown to match results from Monte Carlo scattering
      simulations of the systems. Fluorescence images of mouse brain vasculature,
      obtained using resolution-matched LS-DAC and PS-DAC microscopes, demonstrate the
      comparable performance of LS-DAC and PS-DAC microscopy at shallow depths.

PMID- 24322239
TI  - Efficient and broadband Stokes wave generation by degenerate four-wave mixing at
      the mid-infrared wavelength in a silica photonic crystal fiber.
AB  - Based on degenerate four-wave mixing (FWM), the broadband Stokes waves are
      efficiently generated at the mid-infrared wavelength above 2 MUm, for the first
      time to our knowledge, by coupling the femtosecond pulses into the fundamental
      mode of a silica photonic crystal fiber designed and fabricated in our
      laboratory. Influences of the power and wavelength of pump pulses on the phase
      matched frequency conversion process are discussed. When pump pulses with central
      wavelength of 815 nm and average power of 300 mW are used, the output power ratio
      of the Stokes wave generated at 2226 nm and the residual pump wave P(s)/P(res) is
      estimated to be 10.8:1, and the corresponding conversion efficiency eta(s) and
      bandwidth B(s) of the Stokes wave can be up to 26% and 33 nm, respectively. The
      efficient and broadband Stokes waves can be used as the ultrashort pulse sources
      for mid-infrared photonics and spectroscopy.

PMID- 24322240
TI  - High conversion efficiency microwave photonic mixer based on stimulated Brillouin
      scattering carrier suppression technique.
AB  - A new microwave photonic mixer that can achieve a high conversion efficiency is
      presented. It is based on using the stimulated Brillouin scattering loss spectrum
      to suppress the optical carrier at the output of two optical phase modulators
      driven by the RF signal and the LO, respectively. Experimental results are
      presented, which demonstrate a high conversion efficiency of 11.3 dB
      corresponding to over 26 dB improvement compared to the conventional dual-series
      Mach-Zehnder modulator based microwave photonic mixer, and wide bandwidth of 0.2
      to 20 GHz mixing operation.

PMID- 24322241
TI  - Calculation of the volumetric diffracted field with a three-dimensional
      convolution: the three-dimensional angular spectrum method.
AB  - The first Rayleigh-Sommerfeld diffraction formula is treated in an exact form as
      a three-dimensional (3D) convolution in the spatial domain. Therefore, a 3D
      Fourier transform can be employed to convert the 3D diffracted electromagnetic
      field to the reciprocal space without approximations, which we call the 3D
      angular spectrum (3D-AS) method. It is also demonstrated that if evanescent waves
      are neglected, the 3D-AS method can be readily implemented numerically, with the
      results in good agreement with theoretical predictions. 

PMID- 24322242
TI  - Mutual interferometric characterization of a pair of independent electric fields.
AB  - We demonstrate a novel interferometric characterization scheme that allows the
      complete reconstruction of two interfering electric fields. The phase profiles of
      both beams, and their relative phase, can be retrieved simultaneously as a
      function of any degree of freedom in which it is possible to shear one of the
      beams. The method has applications in wavefront sensing or ultrashort-pulse
      measurement, especially also in the domain of extreme light sources where it is
      difficult to generate a reference field or to replicate the beam in order to
      perform a self-referencing measurement. We demonstrate the technique
      experimentally by measuring simultaneously two ultrashort pulses in a single
      laser shot. 

PMID- 24322243
TI  - Multifocal intraocular lens providing optimized through-focus performance.
AB  - A widespread type of multifocal intraocular lens (MIOL) is based on expanding the
      depth of focus with specific amounts of spherical aberration. However, knowing
      the optimal wavefront aberration for multifocality does not directly provide a
      MIOL geometry. To overcome this issue, we present a new strategy to design MIOLs.
      The method optimizes directly the IOL surface geometries (aspheres with
      aspherical coefficients up to tenth order) using a multisurface pseudophakic eye
      model and a multiconfiguration approach, where the merit function jointly
      considers the optical quality at different object plane locations. An example of
      MIOL [22 diopters (D) far distance correction] was designed. For this design, the
      ocular modulator transfer function (MTF) at 50 cycles per millimeter remained
      above 0.47 for all object locations. The design provides high optical quality
      performance for far and intermediate distances and peak optical performance at
      near distances (MTF>0.57). Additionally, the design shows good performance
      against pupil changes (3-5 mm pupil diameter range). Finally, when the MIOL was
      tested on pseudophakic eye models with corneal spherical aberrations within a
      typical population range, the high multifocal performance was maintained in
      almost 40% of potential patients (ignoring asymmetric aberrations effects).

PMID- 24322244
TI  - Distributed feedback lasing of commercial liquid scintillators.
AB  - It is shown that lasing can be achieved in commercial organic liquid
      scintillators. Using a dynamic grating induced by an interference pattern in the
      scintillator volume, distributed feedback lasing is shown to occur in four out of
      five commercial liquid scintillators that have been investigated. Although these
      scintillators are not designed for lasing application, their purpose being to
      measure radioactivity, induction of a laser effect, furthermore with a tuning
      range of approximately 30 nm, has been attained.

PMID- 24322245
TI  - Dielectric bow-tie nanocavity.
AB  - We propose a novel dielectric bow-tie (DBT) nanocavity consisting of two opposing
      tip-to-tip triangle semiconductor nanowires, whose end faces are coated by silver
      nanofilms. Based on the advantages of the dielectric slot and tip structures, and
      the high reflectivity of the silver mirror, light can be confined in this
      nanocavity with low loss. We demonstrate that at 4.5 K (300 K) around the
      resonance wavelength of 1550 nm, the mode excited in this nanocavity has a deep
      subwavelength mode volume of 2.8*10(-4) MUm3 and a high quality factor of
      4.9*10(4) (401.3), corresponding to an ultrahigh Purcell factor of 1.6*10(7)
      (1.36*10(5)). This DBT nanocavity may find applications for integrated
      nanophotonic circuits, such as high-efficiency single photon sources,
      thresholdless nanolasers, and strong coupling in cavity quantum electrodynamics
      experiments.

PMID- 24322246
TI  - Cavity-sensitive amplified spontaneous emission with radiation reabsorption.
AB  - We experimentally and numerically investigate amplified spontaneous emission
      (ASE) in the presence of radiation reabsorption by using an end-pumped ruby
      laser. From the fluorescence time decay in the axial direction, we find that the
      average path length of ASE is much larger than the reabsorption length and
      exhibits sharp variation near the semi-concentric cavity configuration; however,
      the side lifetime is independent of cavity configuration. In addition, an axial
      power bump corresponding to a side power valley and the enhanced fluorescence R
      line spectrum are observed and explained. 

PMID- 24322247
TI  - Local terahertz microspectroscopy with lambda/100 spatial resolution.
AB  - We have extended the spectral range of a differential method of infrared
      microspectroscopy in order to operate in the terahertz spectral region. We show
      on samples of graphite embedded in a matrix of polymers that the spatial
      resolution is practically independent of the wavelength and is at least
      lambda/100. This method aims at performing "chemical mapping" of various objects
      since it is sensitive only to the imaginary part of the index of refraction. 

PMID- 24322248
TI  - Experimental demonstration of vortex phase-induced reduction in scintillation of
      a partially coherent beam.
AB  - We carry out experimental measurement of the scintillation index of a partially
      coherent beam-carrying vortex phase (i.e., Gaussian-Schell model vortex beam)
      propagating through thermally induced turbulence. It is demonstrated that a
      Gaussian-Schell model vortex beam has appreciably smaller scintillation than a
      Gaussian-Schell model beam, which will be useful in free-space optical
      communication. 

PMID- 24322249
TI  - Cross-phase modulational instability induced by Raman scattering in highly
      birefringent fiber.
AB  - We report experimental and theoretical studies of Raman-induced cross-phase
      modulational instabilities (XPMI) in a high-birefringence, normally dispersive
      optical fiber. Experimental results reveal that the Raman-Stokes wave, generated
      by a quasi-CW pump beam, interacts with the latter to create a novel type of XPMI
      sidebands. These sidebands are characterized by a narrow gain bandwidth. The
      sideband frequencies are well reproduced by a linear stability analysis as well
      as by full numerical solutions of the coupled generalized nonlinear Schrodinger
      equations. 

PMID- 24322250
TI  - Pair-by-pair pulse shaping for optical arbitrary waveform generation by dual-comb
      heterodyne.
AB  - We present a novel optical arbitrary waveform generation approach based on pair
      by-pair pulse shaping. Based on the heterodyne between a pair of optical
      frequency combs with different repetition rates, the repetition rate of the
      generated signals can be flexibly tuned from MHz to GHz without changing the
      setup. The restriction of the spectral resolution of the optical spectrum
      processor is overcome by the pair-by-pair approach while the spectral resolution
      of the system can be improved to MHz by dual-comb heterodyne. Hyperfine control
      of a higher resolution spectrum at MHz is achieved, which benefits the generation
      of the ultrawideband signals. 

PMID- 24322251
TI  - Laser-speckle-based detection of fluid pulsation in the presence of motion
      artifacts: in vitro and in vivo study.
AB  - We have performed an in vitro and in vivo study, based on laser speckle contrast
      analysis, to detect fluid pulsation in the presence of artifacts caused by the
      relative motion between the sample and the illumination source. We observe that
      the pulsation signal is clearly detectable for a range of motion amplitudes and
      oscillation frequencies; however, for higher amplitudes and oscillation
      frequencies of motion, the signal, due to pulsation, becomes increasingly
      difficult to detect. 

PMID- 24322252
TI  - Incoherent resonant seeding of modulation instability in optical fiber.
AB  - We report control of the spectral and noise properties of spontaneous modulation
      instability (MI) in optical fiber using an incoherent seed with power at the 10(
      6) level relative to the pump. We sweep the seed wavelength across the MI gain
      band, and observe significant enhancement of MI bandwidth and improvement in the
      signal-to-noise ratio as the seed coincides with the MI gain peak. We also vary
      the seed bandwidth and find a reduced effect on the MI spectrum as the seed
      coherence decreases. Stochastic nonlinear Schrodinger equation simulations of
      spectral and noise properties are in excellent agreement with experiment.

PMID- 24322253
TI  - Broadband charge transfer dynamics in P3HT:PCBM blended film.
AB  - Broadband exciton dynamics in P3HT:PCBM blended film was observed by the
      femtosecond time-resolved photoluminescence sum-frequency technique. Onsager
      Braun theory is applied to analyze the distribution of charge transfer radius at
      different energy levels. In our evaluation, the optimal diameter of P3HT fiber is
      about 14.3 nm for achieving the best exciton dissociation in P3HT:PCBM blended
      films. This technique can be readily used in the optimization of high-efficiency
      organic photovoltaics.

PMID- 24322254
TI  - Transverse modes of a laser using volume Bragg grating as the cavity mirror.
AB  - A simulation and experiment were performed to demonstrate that a laser using
      volume Bragg grating as one of the cavity mirrors can achieve lasing even if the
      laser cavity length exceeds the traditional stable cavity condition. The laser
      transverse mode changes from a Gaussian beam into a ring-shaped mode as the laser
      cavity length increases from stable to unstable cavity conditions. At the same
      time, the effective modal reflectivity is reduced as the cavity length increases.

PMID- 24322255
TI  - Fiber-laser-based green-pumped picosecond MgO:sPPLT optical parametric
      oscillator.
AB  - We report a stable, high-power, picosecond optical parametric oscillator (OPO) at
      160 MHz repetition rate synchronously pumped by a frequency-doubled mode-locked
      Yb-fiber laser at 532 nm and tunable in the near-infrared, across 874-1008 nm
      (signal) and 1126-1359 nm (idler). Using a 30-mm-long MgO:sPPLT crystal, the OPO
      provides average output power up to 780 mW in the signal at 918.58 nm and 600 mW
      in the idler at 1242 nm. The device operates stably over many days, even close to
      degeneracy, exhibiting passive long-term power stability better than 1.8% rms in
      the signal and 2.4% rms in the idler over 2.5 h at a temperature of 55 degrees C.
      We investigate spectral and temporal characteristics of the signal pulses under
      different conditions and demonstrate cavity-length tuning enabled by the
      dispersion properties of MgO:sPPLT. The output signal pulses have a duration of
      2.4 ps at 967 nm.

PMID- 24322256
TI  - Demonstration of heterogeneous III-V/Si integration with a compact optical
      vertical interconnect access.
AB  - Heterogeneous III-V/Si integration with a compact optical vertical interconnect
      access is fabricated and the light coupling efficiency between the III-V/Si
      waveguide and the silicon nanophotonic waveguide is characterized. The III-V
      semiconductor material is directly bonded to the silicon-on-insulator (SOI)
      substrate and etched to form the III-V/Si waveguide for a higher light
      confinement in the active region. The compact optical vertical interconnect
      access is formed through tapering a III-V and an SOI layer in the same direction.
      The measured III-V/Si waveguide has a light coupling efficiency above ~90% to the
      silicon photonic layer with the tapering structure. This heterogeneous and light
      coupling structure can provide an efficient platform for photonic systems on
      chip, including passive and active devices.

PMID- 24322257
TI  - Reducing bit-error rate with optical phase regeneration in multilevel modulation
      formats.
AB  - We investigate theoretically the benefits of using all-optical phase regeneration
      in a long-haul fiber optic link. We also introduce a design for a device capable
      of phase regeneration without phase-to-amplitude noise conversion. We simulate
      numerically the bit-error rate of a wavelength division multiplexed optical
      communication system over many fiber spans with periodic reamplification and
      compare the results obtained with and without phase regeneration at half the
      transmission distance when using the new design or an existing design. Depending
      on the modulation format, our results suggest that all-optical phase regeneration
      can reduce the bit-error rate by up to two orders of magnitude and that the
      amplitude preserving design offers a 50% reduction in bit-error rate relative to
      existing technology. 

PMID- 24322258
TI  - Competing four-wave mixing processes in dispersion oscillating telecom fiber.
AB  - We experimentally study the dynamics of the generation of multiple sidebands by
      means of a quasi-phase-matched four-wave mixing (FWM) process occurring in a
      dispersion-oscillating, highly nonlinear optical fiber. The fiber under test is
      pumped by a ns microchip laser operating in the normal average group-velocity
      dispersion regime and in the telecom C band. We reveal that the growth of higher
      order sidebands is strongly influenced by the competition with cascade FWM
      between the pump and the first-order quasi-phase matched sidebands. The
      properties of these competing FWM processes are substantially affected when a
      partially coherent pump source is used, leading to a drastic reduction of the
      average power needed for sideband generation. 

PMID- 24322259
TI  - Photonic generation of a phase-coded microwave signal based on a single dual
      drive Mach-Zehnder modulator.
AB  - A compact scheme for photonic generation of a phase-coded microwave signal using
      a dual-drive Mach-Zehnder modulator (DMZM) is proposed and experimentally
      demonstrated. In the proposed scheme, the radio frequency (RF) carrier and the
      coding signal are sent to the two RF ports of the DMZM, respectively. By properly
      setting the amplitude of the coding signal and the bias voltage of the DMZM, an
      exact pi-phase-shift phase-coded microwave signal is generated. The proposed
      scheme has a simple structure since only a single DMZM is required. In addition,
      good frequency tunability is achieved because no frequency-dependent electrical
      devices or wavelength-dependent optical devices are applied. The feasibility of
      the proposed scheme is verified by experiment. 2 or 2.5 Gb/s phase-coded 10 and
      20 GHz microwave signals are successfully generated.

PMID- 24322260
TI  - Synchronous control of dual-channel all-optical multistate switching.
AB  - We have experimentally observed optical multistabilities (OMs) simultaneously on
      both the signal and generated Stokes fields in an optical ring cavity with a
      coherently prepared multilevel atomic medium. The two observed OMs, which are
      governed by different physical processes, are coupled via the multilevel atomic
      medium and exhibit similar threshold behaviors. By modulating the cavity input
      (signal) field with positive or negative pulses, dual-channel all-optical
      multistate switching has been realized and synchronously controlled, which can be
      useful for increasing communication and computation capacities. 

PMID- 24322261
TI  - Pump pulse width and temperature effects in lithium niobate for efficient THz
      generation.
AB  - We present a study on THz generation in lithium niobate pumped by a powerful and
      versatile Yb:CaF(2) laser. The unique laser system delivers transform-limited
      pulses of variable duration (0.38-0.65 ps) with pulse energies up to 15 mJ and
      center wavelength of 1030 nm. From previous theoretical investigations, it is
      expected that such laser parameters are ideally suited for efficient THz
      generation. Here, we present experimental results on both the conversion
      efficiency and the THz spectral shape for variable pump pulse durations and for
      different crystal temperatures, down to 25 K. We experimentally verify the
      optimum pump parameters for the most efficient and broadband THz generation.

PMID- 24322262
TI  - 2.8 W end-pumped Yb3+:LiYF4 waveguide laser.
AB  - Continuous wave, room temperature laser oscillation around 1 MUm is reported for
      the first time (to our knowledge) from an Yb(3+)-doped fluoride crystalline
      waveguide fabricated by using the liquid phase epitaxy technique. Maximum slope
      efficiencies of 76% and 41% were obtained for laser emissions at 994 and 1020 nm,
      respectively. A maximum output power of 2.8 W was obtained at 1020 nm by pumping
      around 980 nm with a high-brightness fiber laser in an 87 mm long V-shaped
      cavity.

PMID- 24322263
TI  - Ghost imaging with shaped incoherent sources.
AB  - We show that the image quality of ghost imaging (GI) can be controlled by the use
      of shaped incoherent sources. The formula for the point-spread function in the GI
      system has been derived and is determined by the Fourier transform of the source
      intensity distribution. Compared with the widely used Gaussian Schell-model
      source, we find that using a cosine-Gaussian Schell-model source can lead to the
      degradation of GI quality, while the quality of GI can be increased with a cosh
      Gaussian Schell-model source. Even under atmospheric turbulence, the image
      resolution of GI still can be improved by means of the cosh-Gaussian Schell-model
      source. 

PMID- 24322264
TI  - Optical fiber-based sensor for in situ monitoring of cadmium sulfide thin-film
      growth.
AB  - This work presents a scheme for in situ monitoring of thin-film growth. A fiber
      optic sensor based on Fabry-Perot interferometric technique has been established
      for the first time to monitor in situ growth of thin films. This was applied for
      determining thickness of cadmium sulfide (CdS) thin films during growth. The
      fabrication process of CdS film was carried out in 30 mM cadmium acetate and
      thioacetamide solution at 60 degrees C temperature. The estimated thickness
      determined during the growth was verified by scanning electron microscopy. This
      study shows that in situ measurement of the thickness of thin films is feasible
      by this new technique, and a close match of the estimated thickness was achieved.

PMID- 24322265
TI  - Super-resolution with complex masks using a phase-only LCD.
AB  - Two methods to achieve super-resolution with complex masks displayed in one-phase
      only liquid crystal display (LCD) are described. The first method decomposes the
      complex mask into two phase-only elements with a posterior recombination using an
      interferometer, and the second method simultaneously encodes the amplitude and
      the phase by modulating the amplitude of the carrier phase. Experimental results
      are presented using a liquid crystal on silicon spatial light modulator under
      reflection. 

PMID- 24322266
TI  - Extraordinary optical absorption based on guided-mode resonance.
AB  - We propose a novel structure that can achieve extraordinary optical absorption
      over the visible spectrum, based on the guided-mode resonance effect. An optical
      metal grating with moderate thickness and high filling factor can lead to
      coupling between the quasi-guided-mode and cavity mode. The resonant interaction
      between the two modes can influence the field distribution, such as the magnetic
      field near the grating, which results in extraordinary absorption. Absorption
      efficiency can be optimized up to 99.16%. We also show that the absorption peak
      can be readily tuned just by varying the subwavelength grating period. 

PMID- 24322267
TI  - Ultra-high temperature chirped fiber Bragg gratings produced by gradient
      stretching of viscoelastic silica.
AB  - By applying a suitable quadratic temperature distribution at a temperature within
      the viscoelastic softening region for silica, a regenerated chirped grating with
      bandwidth of 9.8 nm is produced from a uniform grating using post strain-tuning
      under load. Simulated and experimental results are in good agreement.

PMID- 24322268
TI  - Measuring mechanical strain and twist using helical photonic crystal fiber.
AB  - Solid-core photonic crystal fiber (PCF) with a permanent helical twist exhibits
      dips in its transmission spectrum at certain wavelengths. These are associated
      with the formation of orbital angular momentum states in the cladding. Here we
      investigate the tuning of these states with mechanical torque and axial tension.
      The dip wavelengths are found to scale linearly with both axial strain and
      mechanical twist rate. Analysis shows that the tension-induced shift in resonance
      wavelength is determined both by the photoelastic effect and by the change in
      twist rate, while the torsion-induced wavelength shift depends only on the change
      in twist rate. Twisted PCF can act as an effective optically monitored torque
      tension transducer, twist sensor, or strain gauge. 

PMID- 24322270
TI  - Quantifying genetically inserted fluorescent protein in single iPS cells to
      monitor Nanog expression using electroactive microchamber arrays.
AB  - Interest in the gene expression levels of pluripotent stem cells has increased in
      order to precisely understand cellular differentiation. Here, we propose a method
      utilizing a large number of arrayed microchambers to quantitatively measure an
      intracellular fluorescence protein that is genetically inserted to monitor a
      pluripotency marker protein, Nanog, in pluripotent stem cells. Individual cells
      are isolated and lysed by inducing an electric potential on the cell membrane
      within the tightly enclosed microchambers. The microchambers have a size that is
      comparable to the target cells, making it possible to trap single cells and
      restrict the dilution of the cell lysate. The amount of intracellular
      fluorescence proteins in a single cell is precisely quantified inside the well
      defined volume of each microchamber. Our method will be a useful tool for high
      throughput and parallelized read-outs of gene expression levels in individual
      cells in a large population of cells. 

PMID- 24322269
TI  - Drug labeling and exposure in neonates.
AB  - IMPORTANCE: Federal legislation has led to a notable increase in pediatric
      studies submitted to the Food and Drug Administration (FDA), resulting in new
      pediatric information in product labeling. However, approximately 50% of drug
      labels still have insufficient information on safety, efficacy, or dosing in
      children. Neonatal information in labeling is even scarcer because neonates
      comprise a vulnerable subpopulation for which end-point development is lagging
      and studies are more challenging. OBJECTIVE: To quantify progress made in
      neonatal studies and neonatal information in product labeling as a result of
      recent legislation. DESIGN, SETTING, AND PARTICIPANTS: We identified a cohort of
      drug studies between 1997 and 2010 that included neonates as a result of
      pediatric legislation using information available on the FDA website. We
      determined what studies were published in the medical literature, the legislation
      responsible for the studies, and the resulting neonatal labeling changes. We then
      examined the use of these drugs in a cohort of neonates admitted to 290 neonatal
      intensive care units (NICUs) (the Pediatrix Data Warehouse) in the United States
      from 2005 to 2010. EXPOSURE: Infants exposed to a drug studied in neonates as
      identified by the FDA website. MAIN OUTCOMES AND MEASURES: Number of drug studies
      with neonates and rate of exposure per 1000 admissions among infants admitted to
      an NICU. RESULTS: In a review of the FDA databases, we identified 28 drugs
      studied in neonates and 24 related labeling changes. Forty-one studies
      encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of
      the 24 neonatal labeling changes established safety and effectiveness. In a
      review of a cohort of 446,335 hospitalized infants, we identified 399 drugs used
      and 1,525,739 drug exposures in the first 28 postnatal days. Thirteen (46%) of
      the 28 drugs studied in neonates were not used in NICUs; 8 (29%) were used in
      fewer than 60 neonates. Of the drugs studied, ranitidine was used most often
      (15,627 neonates, 35 exposures per 1000 admissions). CONCLUSIONS AND RELEVANCE:
      Few drug labeling changes made under pediatric legislation include neonates. Most
      drugs studied are either not used or rarely used in US NICUs. Strategies to
      increase the study of safe and effective drugs for neonates are needed.

PMID- 24322271
TI  - From isotope labeled CH3CN to N2 inside single-walled carbon nanotubes.
AB  - The observation of one-dimensional N2 inside single-walled carbon nanotubes
      raises the questions, how are the N2 molecules formed and how do they manage to
      make their way to this peculiar place? We have used N(15) and C(13) isotope
      labeled acetonitrile during the synthesis of single-walled carbon nanotubes to
      investigate this process. The isotope shifts of phonons and vibrons are observed
      by Raman spectroscopy and X-ray absorption. We identify the catalytic
      decomposition of acetonitrile as the initial step in the reaction pathway to
      single-walled carbon nanotubes containing encapsulated N2.

PMID- 24322272
TI  - A comparison of methods for measuring rectal HIV levels suggests that HIV DNA
      resides in cells other than CD4+ T cells, including myeloid cells.
AB  - We compared different techniques for measuring gut HIV reservoirs and assessed
      for HIV in non-CD4 T cells. HIV DNA levels were similar when measured from rectal
      biopsies and isolated rectal cells, while HIV RNA tended to be higher in rectal
      cells. HIV DNA levels in total rectal cells were greater than those predicted
      from levels in sorted CD4 T cells, suggesting a reservoir in non-CD4 T cells, and
      HIV DNA was detected in sorted myeloid cells (7/7 subjects).

PMID- 24322273
TI  - Cistoid macular edema as first manifestation of sarcoidosis.
AB  - The purpose of this study is to report a case of cystoid macular edema (CME) as a
      rare first manifestation of ocular sarcoidosis after cataract surgery. A 60-year
      old male developed a CME following uneventful phacoemulsification cataract
      extraction on his left eye. It resolved with conventional medical therapy. One
      year later the patient was diagnosed with bilateral CME. Oral corticosteroid
      therapy produced a significant regression. His medical and ocular histories were
      unremarkable and all tests for etiological diagnosis were negative. There were
      inflammation recurrences in his left eye, which were also treated with steroids.
      Optical coherence tomography showed complete resolution of foveal thickening
      without improvement in vision. Four years later, the patient presented with CME
      in both eyes. The laboratory tests included high angiotensin-converting enzyme
      levels and a gallium scan which were also consistent with sarcoidosis.
      Azathioprine was needed for management of ocular involvement, but it was withheld
      due to side-effects. At the present time, the CME is controlled with low-dose
      corticoids. Ocular involvement in sarcoidosis occurs in 20-50 % of patients. CME
      is not often the initial manifestation of the disease, but ocular sarcoidosis may
      present with a wide variety of ocular symptoms in all parts of the eye.
      Therefore, sarcoidosis should be kept in mind when evaluating a patient with
      ocular inflammation.

PMID- 24322274
TI  - Sepsis and the innate-like response.
AB  - Innate-like lymphocytes are a recently described subset of the immune response
      with known antibacterial properties. This human trial in critically ill patients
      provides the first evidence of the drop in MAIT cells during bacterial sepsis,
      which compounds the already known immune defects. The persistent depletion and
      potential for nosocomial infections is an interesting finding and one likely to
      provide fertile grounds for future studies.

PMID- 24322275
TI  - Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill
      patients with severe infections.
AB  - PURPOSE: In between innate and adaptive immunity, the recently identified innate
      like mucosal-associated invariant T (MAIT) lymphocytes display specific
      reactivity to non-streptococcal bacteria. Whether they are involved in bacterial
      sepsis has not been investigated. We aimed to assess the number and the time
      course of circulating innate-like T lymphocytes (MAIT, NKT and gammadelta T
      cells) in critically ill septic and non-septic patients and to establish
      correlations with the further development of intensive care unit (ICU)-acquired
      infections. METHODS: We prospectively enrolled consecutive patients with severe
      sepsis and septic shock. Controls were critically ill patients with non-septic
      shock and age-matched healthy subjects. Circulating innate-like lymphocytes were
      enumerated using a flow cytometry assay at day 1, 4 and 7. RESULTS: One hundred
      and fifty six patients (113 severe bacterial infections, 36 non-infected patients
      and 7 patients with severe viral infections) and 26 healthy subjects were
      enrolled into the study. Patients with severe bacterial infections displayed an
      early decrease in MAIT cell count [median 1.3/mm(3); interquartile range (0.4
      3.2)] as compared to control healthy subjects [31.1/mm(3) (12.1-45.2)], but also
      to non-infected critically ill patients [4.3/mm(3) (1.4-13.2)] (P < 0.0001 for
      all comparisons). In contrast NKT and gammadelta T cell counts did not differ
      between patients groups. The multivariate analysis identified non-streptococcal
      bacterial infection as an independent determinant of decrease in MAIT cell count.
      Furthermore, the incidence of ICU-acquired infections was higher in patients with
      persistent MAIT cell depletion. CONCLUSIONS: This large human study provides
      valuable information about MAIT cells in severe bacterial infections. The
      persistent depletion of MAIT cells is associated with the further development of
      ICU-acquired infections.

PMID- 24322276
TI  - Mucosal associated invariant T (MAIT) cell: a novel cellular mechanism
      participating in post-aggressive immunodepression.

PMID- 24322277
TI  - Congenital Factor VII Deficiency in Children at Tertiary Health Care Facility in
      Pakistan.
AB  - This study presents the demographics, clinical spectrum, and outcome of patients
      with congenital factor VII (FVII) deficiency at a tertiary care center over a
      period of 12 years. Of the 49 patients, 27 (55%) patients were males.
      Consanguinity was found in 92% of the patients. The median age of symptom onset
      was 2.4 (interquartile range [IQR]: 1.1-6.5) years with a median age of 5.8 (IQR:
      3.1-10) years at diagnosis. Life-threatening complications like intracranial
      bleeding (ICB) and intra-abdominal bleeding (IAB) were observed in 8 (16.4%)
      patients. We found that 11 (55%) of the 20 patients with FVII coagulant activity
      (FVIIc) <1% were either asymptomatic or showed mild phenotype. In contrast, 9
      (53%) of the 17 patients with FVIIc >5% were affected by severe symptoms. Age <1
      year was the only identified risk factor associated with development of life
      threatening bleeding episodes (P = .042; odds ratio 6.46). Overall, 4 (8.2%) died
      as a consequence of ICB (3 patients) and IAB (1 patient).

PMID- 24322278
TI  - Can Admission Neutrophil to Lymphocyte Ratio Predict Infarct-Related Artery
      Patency in ST-Segment Elevation Myocardial Infarction.
AB  - OBJECTIVES: In this study, we aimed to investigate the relationship between
      neutrophil to lymphocyte ratio (NLR) and infarct-related artery (IRA) patency in
      patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A
      total of 349 patients with STEMI were recruited to this retrospective study.
      Baseline characteristics were reviewed. Patency of IRA was evaluated by
      thrombolysis in myocardial infarction flow grade. RESULTS: Of all patients, 293
      patients formed the occluded IRA group and 56 patients formed the patent IRA
      group. The NLR was significantly higher in occluded IRA group (4.4 +/- 4.1 vs 1.9
      +/- 1.1, P < .001). Glucose levels were also higher in occluded IRA group (171.3
      +/- 78.0 vs 144.7 +/- 49.7, P = .022). Regression analysis demonstrated admission
      NLR and plasma glucose levels as independent predictors of IRA patency.
      CONCLUSION: In this study, we found that admission NLR and glucose levels were
      higher in patients with occluded IRA than in patients with STEMI. We also found
      that NLR and glucose levels were independent predictors of IRA patency. Because
      hemogram is a cheap, fast, and widely available test, it can be used in daily
      practice as a predictor of IRA patency.

PMID- 24322279
TI  - [50th anniversary of the establishment of poliomyelitis vaccination campaigns in
      Spain].

PMID- 24322280
TI  - [Epidemiological studies on the poliomyelitis in Spain before the vaccination].
AB  - The eradication of polio in Spain is one of the most important health milestones
      of the twentieth century, not only for public health but also for the effect it
      had on scientific knowledge in our country, in the medical field. Knowledge of
      international literature by our epidemiologists and virologists, was important,
      as reflected in the studies of outbreaks, virological studies and clinical
      studies. For public health represented, throughout the twentieth century, an
      effort geared to make decisions based on scientific knowledge. For epidemiology
      represented the application of new ways of working and, therefore, its
      modernization. 

PMID- 24322281
TI  - [Poliovirus immunology: vaccines, problems for the prevention/eradication and
      future interventions].
AB  - Polio is a contagious disease that is caused by the poliovirus, an enterovirus in
      the family Picornaviridae. The virus enters through the oral mucosa and
      multiplies in epithelial cells of both the oropharynx as the gastrointestinal
      tract, releasing virus in oropharyngeal secretions and through the stool. The
      mode of transmission is fecal-oral and/or oral-oral. The virus preferentially
      infects children under 5 years. Most infections are asymptomatic and self
      limiting gastrointestinal tract. Eventually it spreads to the central nervous
      system and affects the anterior horn motor neurons of the spinal cord causing
      paralysis and even death. We will describe host-virus interaction and the natural
      history of infection which depends on many factors, including the type of viral
      inoculum (serotypes VP1, 2 and 3) and host factors, such as nutritional status,
      concurrent infections and the ability to induce protective immune responses, such
      as, humoral anti-viral antibody responses with neutralizing antibodies, mucosal
      immunity and systemic adaptative immune responses. We will discuss the relevant
      aspects of the immuno-pathogenesis of the infection by poliovirus and the
      problems related to the host-virus interactions in the subjects vaccinated, with
      the latest advances in the strategies to develop optimal protection with the
      different poliovirus vaccines that could allow the development of a more
      effective immunization with induction of the effect or mechanisms that would
      prevent development of the disease, transmission of the virus, out-breaks and
      eventually the poliovirus eradication. 

PMID- 24322282
TI  - [Gestation and conduct of the First National Campaign of oral polio vaccination
      in Spain].
AB  - This paper presents the intervention of Dr Luis Valenciano Clavel in the act that
      was held on July 2, 2013 under the title Celebrating the 50th anniversary of the
      establishment of poliovirus vaccination campaigns in Spain. (Tribute to Dr D
      Florencio Perez Gallardo), in Ernest Lluch Hall of the Ministry of Health, Social
      Services and Equality. Dr Luis Valenciano Clavel describes his experience and
      direct participation, along with Florencio Perez Gallardo, during the first oral
      polio vaccination campaign in Spain, after returning from his stay in health
      centers of Germany and assuming the leadership of the Polio Diagnostic Laboratory
      of theNational School of Public Health. The success of the polio vaccination
      campaign, it gave rise to the current National Center of Virology, pivot of the
      current Institute of Health Carlos III. 

PMID- 24322283
TI  - [Last phase: eradication].
AB  - This article presents what is considered the last phase of the eradication of
      polio in Spain, which took 25 years during the period 1963-1988, in the wake of
      the sharp decline that occurred in the incidence of the disease by introducing
      Sabin attenuated vaccine in 1963. This should have led to the disappearance of
      the disease in a short period of time, although it was not due to decreased
      vaccination and epidemiological surveillance until 1976. The last indigenous case
      was in 1988. In 1982 Rafael Najera assumed the leadership of the National Center
      of Microbiology, Virology and Immunology Health, the first goal of his team was
      the eradication of polio from our country, introducing the criteria of WHO
      classification and characterization studies of intertipica virus isolates. 

PMID- 24322284
TI  - [Role of the National Poliovirus Laboratory for the Program of eradication and
      poliomyelitis surveillance].
AB  - The Spanish acute flaccid paralysis surveillance network is coordinated by the
      National Poliovirus Laboratory (NPL), which, since 1998, carries out polioviruses
      (PV) and other enteroviruses detected characterization by cell culture and
      molecular techniques. A total of 110,725 (70046+40679) samples were studied
      between 1998-2012 and enteroviruses were detected in 8% of these. Among these
      enteroviruses 241 PV were characterized as PV Sabin-like, except samples belong
      to an imported poliomyelitis case, all of which were characterised as vaccine
      derived PV type 2. The NPL has carried out the serotyping and the intratypic
      differentiation of all the isolated PV in Spain of any syndrome. It is shown that
      wild PV has not circulated in our country during the 15 years studied and that
      has led to the signing of the Act of the "eradication of poliomyelitis in Spain"
      by WHO in 2001, and the /"certification of the eradication of wild PV free for
      European countries" on 21 June 2002. Currently only 3 countries have endemic
      transmission of wild PV (Pakistan, Afghanistan and Nigeria). Until a complete
      worldwide eradication, was achieved, Spain will actively continue to participate
      in the maintenance of the poliomyelitis eradication infrastructure by monitoring
      and vaccination as well as the wild PV containment plan to avoid the spread of
      wild PV.

PMID- 24322285
TI  - [Current phase of control of epidemiological surveillance of poliomyelitis in
      Spain].
AB  - In Spain, the last case of indigenous wild virus poliomyelitis occurred in 1988.
      Since then cases detected by the surveillance system are either imported cases,
      cases associated with vaccine or OPV derivatives (VDPV). The Plan of Action
      required for Certificate of Achievement of polio eradication began in 1997. The
      activities were agreed with the regions and approved by the Inter-territorial
      Council of Health. The plan integrates epidemiological surveillance and
      laboratory activities: - Implement an effective surveillance system acute flaccid
      paralysis (AFP) in children under 15 years - Achieve and maintain high
      immunization coverage (95% in the primary series in children under 2 years old). 
      Environmental monitoring through surveillance of enteroviruses. In the
      implementation of the Plan in Spain have remained high vaccination coverage and
      concern to avoid susceptible bags in vulnerable populations. Surveillance System
      Acute Flaccid Paralysis in children under 15 years has been consistently
      evaluated by the quality indicators related to the sensitivity, timeliness (in
      reporting and sampling) and the indicators for epidemiological research and
      laboratory. The challenges of polio surveillance are introducing cases: imported
      polio caused by wild poliovirus, vaccine-derived poliovirus (VDPV) or poliovirus
      vaccine. Therefore, all activities should continue until a polio-free world.

PMID- 24322286
TI  - [Polio vaccines, eradication and posterradication].
AB  - Vaccination against polio generates herd immunity (both with the attenuated (OPV)
      and inactivated (IPV) vaccines) and this will allow the eradication of the
      disease. The OPV vaccine produces 2-4 polio cases per cohort of one million
      children and therefore IPV is used in countries that can afford its cost (about
      15 times more expensive than OPV). In 1988 the World Health Assembly established
      the polio eradication goal as "interruption of wild poliovirus transmission". If
      the elimination of wild poliovirus were achieved, the use of OPV will produce
      annually between 250 and 500 cases of polio in the world. From 1999, it was clear
      that eradication would require ending of immunization with OPV. On the 25th of
      January, 2013 it is approved the plan for the eradication and containment of all
      polioviruses, wild or not, so that no child suffers paralytic poliomyelitis. The
      most important landmarks include the lack of wild polio cases after 2014, the
      introduction of at least one dose of IPV in all immunization programs and to
      cease the type 2 OPV vaccination by the end of 2016 and to stop the use of the
      oral bivalent vaccine in 2019. To achieve all this, a complex scientific work and
      economic solidarity will be required. 

PMID- 24322287
TI  - [The eradication of the poliomyelitis in the European Region of the World Health
      Organization].
AB  - Poliomyelitis was considered an important event for the public health since the
      end of XIX century when this disease became epidemic. As soon as vaccines were
      available member states of the World Health Organization (WHO) in the European
      Region started to implement vaccination programmes against polio with an
      important impact in the incidence in this disease. In May 1988, the World Health
      Assembly resolution for the global eradication of poliomyelitis was adopted and
      the mechanisms to oversee the progress in the different WHO Regions were
      established. This article briefly reviews the history of polio in the WHO
      European Region, the process for certification and maintenance, the strategies
      for eradication and the current situation in the European Region and globally.
      The European Region was certified polio-free in 2002. Nevertheless, there are
      still three endemic countries in the world, some others use live attenuated
      vaccines as well as countries in the Horn of Africa are recently suffering the
      reintroduction of wild poliovirus. Considering these circumstances, the risk of
      reintroduction of poliovirus and the generation of outbreaks in the European
      Region exists, therefore high vaccination coverage against polio and good quality
      surveillance systems are needed to be guaranteed in every member state. 

PMID- 24322288
TI  - [Polio paralytic. New problems: postpolio syndrome].
AB  - In 1875 M. Raymond described a progressive muscle wasting and weakness in 3
      individuals survivors of childhood acute poliomyelitis. Jean-Martin Charcot
      suggested that the initial injury should let these guys neurons more sensitive to
      develop posterior spinal diseases and new weakness was the result of overuse of
      the affected muscles. In 1979, after the publication of the description given by
      a 57 year old patient on motor difficulties that developed after suffering of
      polio in childhood, there was a very significant increase of comments of other
      individuals with similar symptoms, reaching wedged in the 80s the term of post
      polio syndrome. The term is reserved for describing the development of new
      neurological symptoms, especially for the development of muscle weakness, muscle
      atrophy and new muscle fatigue not explained by other medical causes, and appear
      after more than 15 years of infection acute. Is estimated to affect 20 to 85% of
      individuals with a history of polio in childhood. In 2000 first described the
      diagnostic criteria. This syndrome determines a change in the functional
      abilities. Its pathogenesis is unknown, may be associated with aging. It could
      also be due to an inflammatory persistent or be influenced by genetic factors.
      There is no effective drug treatment, so I can only recommend symptomatic and
      moderate muscle training.

PMID- 24322289
TI  - [Results of the Spanish National Campaign of oral vaccination polio 1963-1964:
      virological and epidemiological study].
AB  - BACKGROUND: From the results of epidemiological studies in 1958 was decided to
      use oral vaccine Sabinl type. The aim of this work is to evaluate the impact of
      the national vaccination campaign of 1963 and 1964. METHODS: The national
      campaign offering it to all Spanish children between two months and seven years.
      In the first phase of the national campaign was employed polio virus type 1 and
      4,400,000 children were vaccinated, ie 95% of the target population. In the
      second phase was trivalent vaccine types 1, 2 and 3 and covered 4,680,000
      children, representing 98.8 per 100. RESULTS: In the first phase 26 polio cases
      occurred in vaccinated children, 18 had been produced by the virus type 3 and
      type 2. In phase 2 were confirmed virologically 27. From 1 June to 31 December
      1964 14 cases were confirmed. 9 in unvaccinated people, 4 received a single dose
      of oral vaccine and one had received two doses of the campaign. From January 1 to
      October 1, 1965 were confirmed 18 cases, 8 children orally vaccinated and 7 had
      received only one dose of this vaccine, in 3 was unknown vaccination status. In
      children vaccinated with two doses of oral vaccine were 0 cases. CONCLUSION: The
      evolution of polio in our country changed radically since the introduction of
      oral polio vaccine. The annual numbers of cases dropped dramatically,
      disappearing completely seasonal rising incidence curve.

PMID- 24322290
TI  - Larvicidal, ovicidal, and adulticidal efficacy of Erythrina indica (Lam.)
      (Family: Fabaceae) against Anopheles stephensi, Aedes aegypti, and Culex
      quinquefasciatus (Diptera: Culicidae).
AB  - Mosquitoes are the major vector for the transmission of malaria, dengue fever,
      yellow fever, filariasis, schistosomiasis, and Japanese encephalitis. Mosquito
      control is facing a threat because of the emergence of resistance to synthetic
      insecticides. Insecticides of botanical origin may serve as suitable alternative
      biocontrol techniques in the future. In view of the recently increased interest
      in developing plant origin insecticides as an alternative to chemical
      insecticide, this study was undertaken to assess the larvicidal, ovicidal, and
      adulticidal potential of the crude hexane, benzene, chloroform, ethyl acetate,
      and methanol solvent extracts from the medicinal plant Erythrina indica against
      the medically important mosquito vectors, Anopheles stephensi, Aedes aegypti, and
      Culex quinquefasciatus (Diptera: Culicidae). The larval mortality was observed
      after 24 h of exposure. All extracts showed moderate larvicidal effects; however,
      the highest larval mortality was found in methanol extract of leaf of E. indica
      against the larvae of A. stephensi, A. aegypti, and C. quinquefasciatus with the
      LC50 and LC90 values of 69.43, 75.13, and 91.41 ppm and 125.49, 134.31, and
      167.14 ppm, respectively. The mean percent hatchability of the eggs was observed
      after 48 h post treatment. The percent hatchability was inversely proportional to
      the concentration of extract and directly proportional to the eggs. All the five
      solvent extracts showed moderate ovicidal activity; however, the methanol extract
      showed the highest ovicidal activity. The methanol extract of E. indica against
      A. stephensi, A. aegypti, and C. quinquefasciatus exerted 100 % mortality (zero
      hatchability) at 150, 200, and 250 ppm, respectively. Control eggs showed above
      99.3-100 % hatchability. The adult mortality was observed after 24 h recovery
      period. The plant crude extracts showed dose-dependent mortality. At higher
      concentrations, the adult showed restless movement for some times with abnormal
      wagging and then died. Among the extracts tested, the highest adulticidal
      activity was observed in methanol extract against A. stephensi followed by A.
      aegypti and C. quinquefasciatus with the LD50 and LD90 values of 88.76, 94.09,
      and 119.64 ppm and 160.83, 169.01, and 219.77 ppm, respectively. No mortality was
      recorded in the control. Our data suggest that the crude hexane, benzene,
      chloroform, ethyl acetate, and methanol solvent extracts of E. indica have the
      potential to be used as an eco-friendly approach for the control of the A.
      stephensi, A. aegypti, and C. quinquefasciatus.

PMID- 24322291
TI  - Influence of Plasmodium vivax malaria on the relations between the osmotic
      stability of human erythrocyte membrane and hematological and biochemical
      variables.
AB  - This study evaluated the influence of infection by Plasmodium vivax on the
      relations between hematological and biochemical variables and the osmotic
      stability of the erythrocyte membrane in a Brazilian Amazon population. A total
      of 72 patients with P. vivax malaria were included in the study and invited to
      return after 14 days, post-treatment with chloroquine and primaquine, for
      clinical and laboratorial reevaluations. The osmotic stability of the erythrocyte
      membrane was analyzed by nonlinear regression of the dependency of the absorbance
      of hemoglobin, released with hemolysis, as a function of the salt concentration,
      and it was represented by the inverse of the salt concentration at the midpoint
      of the curve (1/H 50) and by the variation of salt concentration, which promotes
      lysis (dX). Bivariate and multivariate methods were used in the analysis of the
      results. Prior to treatment of the disease, the erythrocytes showed greater
      stability, probably due to the natural selection of young and also more stable
      erythrocytes. The bivariate analysis showed that 1/H 50 was positively correlated
      with red cell distribution width (RDW), urea, triglycerides, and very low-density
      lipoprotein (VLDL)-cholesterol, but negatively associated with albumin, HDL
      cholesterol, and indirect bilirubin, while dX was negatively associated with the
      mean corpuscular hemoglobin concentration. These associations were confirmed by
      canonical correlation analysis. Stepwise multiple linear regression showed that
      albumin, urea, triglycerides, and VLDL-cholesterol are the variables with the
      highest abilities of predicting erythrocyte stability. The bivariate analysis
      also showed that the hematological index RDW was related to elevated levels of
      bilirubin and decreased levels of albumin and urea, associated with liver damage
      resulting from malaria.

PMID- 24322292
TI  - Gigantobilharzia melanoidis n.sp. (Trematoda: Schistosomatidae) from Melanoides
      tuberculata (Gastropoda: Thiaridae) in the United Arab Emirates.
AB  - Delicate filamentous schistosomatids detected in the intestinal veins of
      experimentally infected chickens are here described as a new parasite species,
      Gigantobilharzia melanoidis, and details of its life cycle are given. It is the
      first complete description of a schistosome species that uses Melanoides
      tuberculata as an intermediate host. Apharyngeate ocellate brevifurcate cercariae
      found in 65 out of 950 M. tuberculata collected in a pond in Al Aweer, United
      Arab Emirates were used as infection material. The new species can be
      distinguished from the other species of the genus by the following combination of
      characters: caecal reunion in males situated anterior to seminal vesicle, a very
      short gynecophoric canal (gynecophoric canal length/body length ratio lower than
      0.05) supported by 12-14 thickened bands. Cercariae of G. melanoidis can be
      distinguished from other Gigantobilharzia cercariae described in the literature
      based on the combination of these characters: flame cell formula 2[3 + 3 + (1)] =
      14 and relatively longer tail stem in relation to body (tail stem length/body
      length ratio = 2). Under laboratory conditions at a temperature between 24 and 26
      degrees C, M. tuberculata started to shed cercariae 7 weeks after exposure to
      miracidia. The prepatent period of G. melanoidis in experimentally infected
      chicken lasted between 43 and 49 days. The parasite inhabits the blood vessels
      mainly of the small intestine. Sections of adult worms and eggs were also found
      in histocuts of parenchymatous organs. Results of phylogenetic analysis
      corroborated that G. melanoidis is a distinct species; however, they also
      confirmed that the genus Gigantobilharzia is in need of revision and in future
      might be split into several genera.

PMID- 24322293
TI  - Changes in NK and NKT cells in mesenteric lymph nodes after a Schistosoma
      japonicum infection.
AB  - The mesenteric lymph node (MLN) is the main draining lymph node in mouse
      enterocoelia, which contains many types of immune cells. Among these cells,
      natural killer (NK) and natural killer T (NKT) cells belong to innate lymphoid
      cells (ILCs), which have potent activities for controlling a variety of
      pathogenic infections. In this study, C57BL/6 mice were infected with Schistosoma
      japonicum for 5-7 weeks. Lymphocytes were isolated from the MLN to detect changes
      in the phenotype and function of NK and NKT cells using a fluorescence activating
      cell sorter (FACS). These results demonstrated that a S. japonicum infection
      could significantly increase the percentage of NK cells in the mouse MLN, (P <
      0.05). We found an increase in the cell number of both NK and NKT cells. In
      addition, we found that NK and NKT cells from infected mice expressed higher
      levels of CD69 compared to normal mice (P < 0.05). These results demonstrated
      that a S. japonicum infection could induce MLN NK and NKT cell activation.
      Moreover, we found that the expression of CD4 was increased in infected MLN NK
      cells (P < 0.05). Furthermore, intracellular cytokine staining revealed that
      expression of IL-4 and IL-17 were significantly enhanced in both the NK and NKT
      cells of infected mice after phorbol 12-myristate 13-acetate (PMA) and ionomycin
      stimulation (P < 0.05). Taken together, these results indicated that infection
      induced MLN NK and NKT cells might play roles in modulating the classical T cell
      response. Finally, our results indicated that the expression of CD94 was
      decreased in NK cells, suggesting that the downregulation of CD94 expression
      might served as a mechanism in NK cell activation.

PMID- 24322294
TI  - SIOMICS: a novel approach for systematic identification of motifs in ChIP-seq
      data.
AB  - The identification of transcription factor binding motifs is important for the
      study of gene transcriptional regulation. The chromatin immunoprecipitation
      (ChIP), followed by massive parallel sequencing (ChIP-seq) experiments, provides
      an unprecedented opportunity to discover binding motifs. Computational methods
      have been developed to identify motifs from ChIP-seq data, while at the same time
      encountering several problems. For example, existing methods are often not
      scalable to the large number of sequences obtained from ChIP-seq peak regions.
      Some methods heavily rely on well-annotated motifs even though the number of
      known motifs is limited. To simplify the problem, de novo motif discovery methods
      often neglect underrepresented motifs in ChIP-seq peak regions. To address these
      issues, we developed a novel approach called SIOMICS to de novo discover motifs
      from ChIP-seq data. Tested on 13 ChIP-seq data sets, SIOMICS identified motifs of
      many known and new cofactors. Tested on 13 simulated random data sets, SIOMICS
      discovered no motif in any data set. Compared with two recently developed methods
      for motif discovery, SIOMICS shows advantages in terms of speed, the number of
      known cofactor motifs predicted in experimental data sets and the number of false
      motifs predicted in random data sets. The SIOMICS software is freely available at
      http://eecs.ucf.edu/~xiaoman/SIOMICS/SIOMICS.html. 

PMID- 24322296
TI  - PGC7 suppresses TET3 for protecting DNA methylation.
AB  - Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5
      hydroxylmethylcytosine. However, the molecular mechanism that regulates this
      biological process is not clear. Here, we show the evidence that PGC7 (also known
      as Dppa3 or Stella) interacts with TET2 and TET3 both in vitro and in vivo to
      suppress the enzymatic activity of TET2 and TET3. Moreover, lacking PGC7 induces
      the loss of DNA methylation at imprinting loci. Genome-wide analysis of PGC7
      reveals a consensus DNA motif that is recognized by PGC7. The CpG islands
      surrounding the PGC7-binding motifs are hypermethylated. Taken together, our
      study demonstrates a molecular mechanism by which PGC7 protects DNA methylation
      from TET family enzyme-dependent oxidation. 

PMID- 24322295
TI  - FeON-FeOFF: the Helicobacter pylori Fur regulator commutates iron-responsive
      transcription by discriminative readout of opposed DNA grooves.
AB  - Most transcriptional regulators bind nucleotide motifs in the major groove,
      although some are able to recognize molecular determinants conferred by the minor
      groove of DNA. Here we report a transcriptional commutator switch that exploits
      the alternative readout of grooves to mediate opposite output regulation for the
      same input signal. This mechanism accounts for the ability of the Helicobacter
      pylori Fur regulator to repress the expression of both iron-inducible and iron
      repressible genes. When iron is scarce, Fur binds to DNA as a dimer, through the
      readout of thymine pairs in the major groove, repressing iron-inducible
      transcription (FeON). Conversely, on iron-repressible elements the metal ion acts
      as corepressor, inducing Fur multimerization with consequent minor groove readout
      of AT-rich inverted repeats (FeOFF). Our results provide first evidence for a
      novel regulatory paradigm, in which the discriminative readout of DNA grooves
      enables to toggle between the repression of genes in a mutually exclusive manner.

PMID- 24322297
TI  - Causal inference of gene regulation with subnetwork assembly from genetical
      genomics data.
AB  - Deciphering the causal networks of gene interactions is critical for identifying
      disease pathways and disease-causing genes. We introduce a method to reconstruct
      causal networks based on exploring phenotype-specific modules in the human
      interactome and including the expression quantitative trait loci (eQTLs) that
      underlie the joint expression variation of each module. Closely associated eQTLs
      help anchor the orientation of the network. To overcome the inherent
      computational complexity of causal network reconstruction, we first deduce the
      local causality of individual subnetworks using the selected eQTLs and module
      transcripts. These subnetworks are then integrated to infer a global causal
      network using a random-field ranking method, which was motivated by animal
      sociology. We demonstrate how effectively the inferred causality restores the
      regulatory structure of the networks that mediate lymph node metastasis in oral
      cancer. Network rewiring clearly characterizes the dynamic regulatory systems of
      distinct disease states. This study is the first to associate an RXRB-causal
      network with increased risks of nodal metastasis, tumor relapse, distant
      metastases and poor survival for oral cancer. Thus, identifying crucial upstream
      drivers of a signal cascade can facilitate the discovery of potential biomarkers
      and effective therapeutic targets. 

PMID- 24322298
TI  - A critical switch in the enzymatic properties of the Cid1 protein deciphered from
      its product-bound crystal structure.
AB  - The addition of uridine nucleotide by the poly(U) polymerase (PUP) enzymes has a
      demonstrated impact on various classes of RNAs such as microRNAs (miRNAs),
      histone-encoding RNAs and messenger RNAs. Cid1 protein is a member of the PUP
      family. We solved the crystal structure of Cid1 in complex with non-hydrolyzable
      UMPNPP and a short dinucleotide compound ApU. These structures revealed new
      residues involved in substrate/product stabilization. In particular, one of the
      three catalytic aspartate residues explains the RNA dependence of its PUP
      activity. Moreover, other residues such as residue N165 or the beta-trapdoor are
      shown to be critical for Cid1 activity. We finally suggest that the length and
      sequence of Cid1 substrate RNA influence the balance between Cid1's processive
      and distributive activities. We propose that particular processes regulated by
      PUPs require the enzymes to switch between the two types of activity as shown for
      the miRNA biogenesis where PUPs can either promote DICER cleavage via short U
      tail or trigger miRNA degradation by adding longer poly(U) tail. The enzymatic
      properties of these enzymes may be critical for determining their particular
      function in vivo. 

PMID- 24322299
TI  - Characterization of two different Asf1 histone chaperones with distinct cellular
      localizations and functions in Trypanosoma brucei.
AB  - The anti-silencing function protein 1 (Asf1) is a chaperone that forms a complex
      with histones H3 and H4 facilitating dimer deposition and removal from chromatin.
      Most eukaryotes possess two different Asf1 chaperones but their specific
      functions are still unknown. Trypanosomes, a group of early-diverged eukaryotes,
      also have two, but more divergent Asf1 paralogs than Asf1 of higher eukaryotes.
      To unravel possible different functions, we characterized the two Asf1 proteins
      in Trypanosoma brucei. Asf1A is mainly localized in the cytosol but translocates
      to the nucleus in S phase. In contrast, Asf1B is predominantly localized in the
      nucleus, as described for other organisms. Cytosolic Asf1 knockdown results in
      accumulation of cells in early S phase of the cell cycle, whereas nuclear Asf1
      knockdown arrests cells in S/G2 phase. Overexpression of cytosolic Asf1 increases
      the levels of histone H3 and H4 acetylation. In contrast to cytosolic Asf1,
      overexpression of nuclear Asf1 causes less pronounced growth defects in parasites
      exposed to genotoxic agents, prompting a function in chromatin remodeling in
      response to DNA damage. Only the cytosolic Asf1 interacts with recombinant H3/H4
      dimers in vitro. These findings denote the early appearance in evolution of
      distinguishable functions for the two Asf1 chaperons in trypanosomes. 

PMID- 24322301
TI  - BiVO4 thin film photoanodes grown by chemical vapor deposition.
AB  - BiVO4 thin film photoanodes were grown by vapor transport chemical deposition on
      FTO/glass substrates. By controlling the flow rate, the temperatures of the Bi
      and V sources (Bi metal and V2O5 powder, respectively), and the temperature of
      the deposition zone in a two-zone furnace, single-phase monoclinic BiVO4 thin
      films can be obtained. The CVD-grown films produce global AM1.5 photocurrent
      densities up to 1 mA cm(-2) in aqueous conditions in the presence of a
      sacrificial reagent. Front illuminated photocatalytic performance can be improved
      by inserting either a SnO2 hole blocking layer and/or a thin, extrinsically Mo
      doped BiVO4 layer between the FTO and the CVD-grown layer. The incident photon to
      current efficiency (IPCE), measured under front illumination, for BiVO4 grown
      directly on FTO/glass is about 10% for wavelengths below 450 nm at a bias of +0.6
      V vs. Ag/AgCl. For BiVO4 grown on a 40 nm SnO2/20 nm Mo-doped BiVO4 back contact,
      the IPCE is increased to over 40% at wavelengths below 420 nm. 

PMID- 24322300
TI  - Identification of residues required for stalled-ribosome rescue in the codon
      independent release factor YaeJ.
AB  - The YaeJ protein is a codon-independent release factor with peptidyl-tRNA
      hydrolysis (PTH) activity, and functions as a stalled-ribosome rescue factor in
      Escherichia coli. To identify residues required for YaeJ function, we performed
      mutational analysis for in vitro PTH activity towards rescue of ribosomes stalled
      on a non-stop mRNA, and for ribosome-binding efficiency. We focused on residues
      conserved among bacterial YaeJ proteins. Additionally, we determined the solution
      structure of the GGQ domain of YaeJ from E. coli using nuclear magnetic resonance
      spectroscopy. YaeJ and a human homolog, ICT1, had similar levels of PTH activity,
      despite various differences in sequence and structure. While no YaeJ-specific
      residues important for PTH activity occur in the structured GGQ domain, Arg118,
      Leu119, Lys122, Lys129 and Arg132 in the following C-terminal extension were
      required for PTH activity. All of these residues are completely conserved among
      bacteria. The equivalent residues were also found in the C-terminal extension of
      ICT1, allowing an appropriate sequence alignment between YaeJ and ICT1 proteins
      from various species. Single amino acid substitutions for each of these residues
      significantly decreased ribosome-binding efficiency. These biochemical findings
      provide clues to understanding how YaeJ enters the A-site of stalled ribosomes. 

PMID- 24322302
TI  - Transmetallation as an effective strategy for the preparation of bimetallic CoPd
      and CuPd nanoparticles.
AB  - The preparation of palladium alloy nanoparticles is of great interest for many
      applications, especially in catalysis. Starting from presynthesized nanoparticles
      of a less noble metal, a transmetallation reaction involving a redox process at
      the nanoparticle surface can be exploited to modify the nanoparticle composition
      and crystalline phase. As an example, monodispersed epsilon-cobalt and face
      centered cubic copper nanoparticles were synthesized in organic solvents at high
      temperature and the as-formed nanoparticles were reacted with palladium(ii)
      hexafluoroacetylacetonate resulting in the formation of alloyed nanoparticles
      whose composition closely follows the reactant ratio. The oxidative state of the
      nanoparticle surface greatly affects the success of the transmetallation reaction
      and a reduction treatment was necessary to achieve the desired final product.
      Electron microscopy and X-ray diffraction showed that for cobalt a limiting
      palladium content for the epsilon-phase alloy is found, above which an fcc alloy
      nucleates, while for copper the fcc crystalline phase is preserved throughout the
      whole composition range. 

PMID- 24322303
TI  - Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal
      women.
AB  - The estrogen levels of Asian women are different from those of Western women, and
      this could affect estrogen receptor (ER) bioactivity and breast cancer risk. We
      conducted a case-control study in 169 postmenopausal breast cancer cases and 426
      matched controls nested within a population-based prospective cohort study, the
      Singapore Chinese Health Study, to evaluate the serum levels of estrogens and
      their receptor (ERalpha and ERbeta)-mediated estrogenic activities in relation to
      breast cancer risk. Breast cancer cases had higher levels of estrogens and ER
      mediated bioactivities in baseline serum than the controls. Compared with those
      in the lowest quartile, women in the highest quartile for estrone (E1) or ERalpha
      mediated bioactivity had increased breast cancer risk. After additional
      adjustment for ERbeta bioactivity, free estradiol, and E1 levels, serum ERalpha
      mediated bioactivity remained associated with increased breast cancer risk.
      Compared with those in the lowest quartile, women in the highest quartile for
      ERalpha-mediated bioactivity had an odds ratio of 2.39 (95% CI=1.17-4.88; P for
      trend=0.016). Conversely, the positive association between E1 and cancer risk
      became null after adjustment for ERalpha-mediated bioactivity, suggesting that
      the effect of E1 could be mediated through ERalpha. Factor(s) contributing to
      increased ERalpha-mediated estrogenic bioactivity in serum and its role as a
      predictor for breast cancer risk need to be validated in future studies. 

PMID- 24322304
TI  - Incidence of gastroenteropancreatic neuroendocrine tumours: a systematic review
      of the literature.
AB  - Based on the current medical literature, the worldwide incidence of
      neuroendocrine tumours (NETs) seems to have increased; however, a systematic
      literature overview is lacking. This study aimed to collect all available data on
      the incidence of gastroenteropancreatic (GEP)-NETs and characteristics of
      population to establish their epidemiology. A sensitive MEDLINE search was
      carried out. The papers were selected via a cascade process that restricted the
      initial pool of 7991 articles to 33, using predefined inclusion and exclusion
      criteria. Original articles evaluating the incidence of sporadic GEP-NETs in
      regional, institutional and national registries were considered. The majority of
      data originated from the US National Cancer Institute Surveillance, Epidemiology
      and End Results database and from national cancer registries in Western Europe.
      Generally, because of the retrospective nature of existing databases the outcomes
      of studies might be biased, which hinders the drawing of firm conclusions. The
      age-adjusted incidence of GEP-NETs has increased steadily over the past four
      decades (1973-2007), increasing 3.65-fold in the USA and 3.8- to 4.8-fold in the
      UK. Incidence has changed variably from one anatomical site to another. The
      greatest increase in incidence occurred for gastric and rectal NETs, while the
      smallest increase occurred for small intestine NETs. There were gender and racial
      differences, which differed site by site and, in some cases, changed over time.
      The incidence rates (IRs) of GEP-NETs have increased significantly in the last 40
      years. Data are only available from North America, Western Europe and Japan. A
      site-by-site analysis revealed that the IRs of some NETs increased more than
      those of others. 

PMID- 24322305
TI  - Factors associated with aggravation of esophageal varices after B-RTO for gastric
      varices.
AB  - PURPOSE: To retrospectively evaluate risk factors for aggravation of esophageal
      varices (EV) within 1 year after balloon-occluded retrograde transvenous
      obliteration (B-RTO) of gastric varices (GV) and to clarify suitable timing for
      upper endoscopy to detect EV aggravation after B-RTO. METHODS: Participants
      included 67 patients who underwent B-RTO for GV between January 2006 and December
      2010. Whether EV aggravation occurred within 1 year was evaluated, and the time
      interval from B-RTO to aggravation was calculated. Factors potentially associated
      with EV aggravation were analyzed. RESULTS: B-RTO was successfully performed in
      all patients. EV aggravation at 1 year after B-RTO was found in 38 patients (56.7
      %). Multivariate logistic regression analysis showed that total bilirubin (T-bil)
      (P = 0.032) and hepatic venous pressure gradient (HVPG) (P = 0.011) were
      significant independent risk factors for EV aggravation after B-RTO. Cutoff
      values of T-bil and HVPG yielding maximal combined sensitivity and specificity
      for EV aggravation were 1.6 mg/dL and 13 mmHg, respectively. The patients with T
      bil >= 1.6 mg/dL or HVPG >= 13 mmHg had a median aggravation time of 5.1 months.
      All five patients with ruptured EV belonged to this group. In contrast, patients
      with T-bil < 1.6 mg/dL and HVPG < 13 mmHg had a median aggravation time of 21
      months. CONCLUSION: T-bil and HVPG were significant independent risk factors for
      EV aggravation after B-RTO. The patients with T-bil >= 1.6 mg/dL or HVPG >= 13
      mmHg require careful follow-up evaluation, including endoscopy.

PMID- 24322306
TI  - Effect of pitavastatin on preventing ischemic complications with carotid artery
      stenting: a multicenter prospective study--EPOCH-CAS study.
AB  - PURPOSE: Periprocedural ischemic stroke is one problem associated with carotid
      artery stenting (CAS). This study was designed to assess whether preoperative
      statin therapy reduces the risk of periprocedural ischemic complications with
      CAS. METHODS: In this prospective study at 11 centers, patients with carotid
      artery stenosis (symptomatic >=50%, asymptomatic >=80%) and a high risk of
      carotid endarterectomy but without previous statin treatments were divided into
      two groups by low-density lipoprotein cholesterol (LDL-C) levels. With LDL-C
      >=120 mg/dl, the pitavastatin-treated (PS) group received pitavastatin at 4
      mg/day. With LDL-C <120 mg/dl, the non-PS group received no statin therapy. After
      4 weeks, both groups underwent CAS. Frequencies of new ipsilateral ischemic
      lesions on diffusion-weighted imaging within 72 h after CAS and cerebrovascular
      events (transient ischemic attack, stroke, or death) within 30 days were
      assessed. RESULTS: Among the 80 patients enrolled, 61 patients (PS group, n = 31;
      non-PS group, n = 30) fulfilled the inclusion criteria. New ipsilateral ischemic
      lesions were identified in 8 of 31 patients (25.8%) in the PS group and 16 of 30
      patients (53.3%) in the non-PS group (P = 0.028). Cerebrovascular events occurred
      in 0 patients in the PS group and in 3 of 30 patients (10.0%) in the non-PS group
      (P = 0.071). Multivariate analyses demonstrated the pitavastatin treatment (beta
      = 0.74, 95% confidence interval 0.070-1.48, P = 0.042) to be an independent
      factor for decreasing post-CAS ischemic lesions. CONCLUSION: Pretreatment with
      pitavastatin significantly reduced the frequency of periprocedural ischemic
      complications with CAS.

PMID- 24322307
TI  - Temporary distal balloon occlusion for hepatic embolization: a novel technique to
      treat what cannot be selected.
AB  - PURPOSE: Particle embolotherapy for liver cancers, such as chemoembolization and
      yttrium-90 radioembolization, depends on microcatheter selection of the treatment
      vessel for injection of the embolic. Individually selecting vessels with a
      microcatheter can be time-consuming and difficult, especially when multiple
      branches are present in the treatment zone. This article describes a technique to
      perform an "inverse" embolization-protection of the selected vessel and
      embolization of the unselected vessels-a technique that has not yet been
      described. MATERIALS AND METHODS: Two cases of hepatic chemoembolization that
      would require subselection of multiple branch vessels using conventional
      technique are reported. In both cases the proper hepatic artery was selected with
      a soft, nondissecting neurovascular guide catheter. The nontarget hepatic vessel
      was selected with a neurovascular microcatheter occlusion balloon, and the
      balloon was inflated to protect that vessel. Embolization to multiple target
      vessels was then achieved by way of a single injection through the guide
      catheter. RESULTS: Both procedures were technically successful without
      complication. Postembolization angiography confirmed normal parenchymal
      enhancement in the protected zone and expected paucity of enhancement in the
      treated zone. CONCLUSION: Temporary distal balloon occlusion is a useful
      technique to treat multiple artery branches with a single injection in cases
      where individual selection of the branches is difficult or time-consuming.
      Further study of this technique is warranted.

PMID- 24322308
TI  - [The influence of difference of surgical procedure for the young spontaneous
      pneumothorax to the recurrence rate after surgery].
AB  - INTRODUCTION: In spontaneous pneumothorax (SP) in patients under the age of 30,
      we studied the postoperative recurrence rate due to differences in the surgical
      procedures and the patient's age. MATERIALS AND METHODS: Between October 2003 and
      September 2012, 351 operations were performed for the young(30 years or
      younger)SP in our hospital. The recurrence rate was calculated in 2 age groups(
      under 20 or older) with different surgical procedures which were classified into
      5 groups on the basis of the combination of the covering site with the polyglycol
      acid (PGA) seat and the presence or absence of ligation at both ends of staple
      line. RESULTS: The mean age of all patients was 21.0+/-4.4, 320 were male. The
      recurrence rate of all was 8.8%.The group 20 years or younger in comparison with
      the group 21 years or older had significantly high recurrence rate after
      surgery(11.9% v.s. 5.1%;p=0.034).However, covering the staple-line with ligation
      of both ends and covering the staple-line and the bullae common site were both
      significantly lower recurrence rate compared with the group with covering only to
      the staple-line in 20 years or younger group(0% v.s. 23.8%;p=0.041, 4.9% v.s.
      23.8%;p=0.041). CONCLUSION: The results suggest that we need to choose the
      appropriate procedure of the surgery for SP considering the patient's age. The
      recurrence rate in the patient 20 years or younger can be reduced by covering the
      bullae common site and/or the ligating both ends of staple-line in addition to
      covering the staple-line.

PMID- 24322309
TI  - [Early outcomes of isolated aortic valve replacement in octogenarians].
AB  - We retrospectively studied early outcomes of isolated aortic valve replacement
      (AVR)in octogenarians. From November 2006 to October 2012, 70 patients underwent
      AVR and we divided them into 2 groups:group O (24 patients aged 80 years or
      older, 80~91 years;mean age, 85.0 years);and group Y(46 patients aged younger
      than 80, 39~79 years;mean age, 69.0 years). There were no significant differences
      in preoperative comorbidities between the groups, but the logistic EuroSCORE(
      13.5% in the group O, 5.3%in the group Y) and EuroSCORE II (4.5% in the group O,
      1.7% in the group Y) were significantly higher in the group O. The amount of
      blood transfusion needed was greater in the group O, but there were no
      differences between the groups with regard to the operation time, cardiopulmonary
      bypass time or aortic cross-clamp time. Operative mortality (4.2% in the group O,
      2.2%in the group Y)and postoperative complications were not significantly
      different between the groups. Early outcomes of AVR in octogenarians were good
      and the newly refined EuroSCORE II showed a good correlation within the studied
      population.

PMID- 24322310
TI  - [Ultrasound-guided percutaneous thrombin injection therapy for the treatment of
      iatrogenic brachial pseudoaneurysms].
AB  - Iatrogenic pseudoaneurysm could result in rupture or serious complications. The
      treatment of this condition involves the use of ultrasound-guided compression
      therapy;however, when this therapy is not effective, surgical intervention
      becomes necessary. Although ultrasound-guided compression therapy is a minimally
      invasive treatment, the patient might experience pain during the procedure and
      its effectiveness is decreased under anticoagulant therapy. Surgical repair is
      also invasive and is frequently accompanied by several complications. We
      successfully treated 3 cases of iatrogenic pseudoaneurysm on the brachial artery
      (size, 25~45mm) using the ultrasound-guided thrombin injection therapy after the
      ultrasound-guided compression therapy was unsuccessful. Ultrasound-guided
      thrombin injection therapy is an alternative treatment that is highly effective
      with the additional advantage of being a simple and quick procedure with lesser
      burden on the patient. 

PMID- 24322311
TI  - [Neuroleptic malignant syndrome after cardiac surgery].
AB  - A 64-year-old man without any psychiatric disease, including Parkinson's disease
      underwent aortic valve replacement and mitral valve replacement for rheumatic
      valvular disease. One day after the cardiac surgery, he developed hyperthermina,
      muscle rigidity, coma and delirium, and his serum creatine kinase (CK) level was
      elevated. In spite of his negative brain computed tomography(CT), his
      consciousness remained unclear. He had received diazepam, flunitrazepam and
      buprenorphine after the cardiac surgery because of his hyper-reactivity. Although
      these drugs were not typical antipsychotics' causing neuroleptic malignant
      syndrome (NMS), NMS was strongly suspected because of his clinical appearance.
      Dantrolene was administered in a dose of 60 mg per day and he recovered
      consciousness and his CK level began to decrease. We reported a case of
      neuroleptic malignant syndrome after cardiac surgery.

PMID- 24322312
TI  - [Aortic annulus repair with xenogeneic pericardial flap after extensive
      debridement in active prosthetic valve endocarditis associated with an aortic
      annular abscess].
AB  - Prosthetic aortic valve endocarditis(PVE) is one of the devastating diseases and
      some cases present with extensive annular destruction requiring complex surgical
      repair. We report 2 cases of PVE with more than one-half of aortic annular
      destruction after complete debridement of the infected tissue. In these patients
      we successfully performed mechanical valve implantation following annular repair
      using a square piece of xenogeneic pericardium that was soaked in highly
      concentrated vancomycin solution. To increase rigidity of an annulus, a square
      piece of xenogeneic pericardium was interposed into abscess cavity with some
      single interrupted sutures. Sutures were placed along the abscess cavity and tied
      to the fragile tissue carefully. Both patients were discharged from hospital and
      have been doing well without any signs of recurrent endocarditis at a year
      postoperatively. This procedure might enable us to avoid patch closure of the
      abscess cavity in some severe PVE patients. 

PMID- 24322313
TI  - [IgG4-related constrictive pericarditis treated by waffle procedure].
AB  - A 59-year-old man was admitted for evaluation of short of breath and bilateral
      leg edema that had progressively worsened over 3 months. Chest computed
      tomography revealed marked pericardial thickening. Cardiac echocardiography
      revealed right heart volume load and diastolic dysfunction. Cardiac
      catheterization revealed a dip-and-plateau pattern of the pressure curve of right
      ventricule (RV)without any coronary disease. On a diagnosis of heart failure due
      to pericardial constriction, he underwent pericardiectomy under cardiopulmonary
      bypass. Multiple longitudinal and transverse incisions like a waffle were made in
      the thickened epicardium and improved the hemodynamics. The symptoms improved
      after surgery. As serum level of immunoglobulin G(IgG)4 was elevated and IgG4
      positive plasma cells were recognized in the resected pericardium, diagnosis of
      constrictive pericarditis of hyper-IgG4 disease was made. 

PMID- 24322314
TI  - [Coronary Artery Bypass Grafting (CABG) and simultaneous cardiac
      resynchronization therapy in a patient with left ventricular noncompaction
      repeating heart failure].
AB  - Noncompaction of the left ventricular myocardium (NCLV) is a rare congenital
      cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis,
      and has been known as a disease of infants. However, some cases of NCLV in adults
      have been recently reported. We experienced an adult NCLV case repeating heart
      failure, and controlled it by surgery. The patient was 75-year-old man with NCLV
      and he had repeated heart failure and hospitalization. His heart failure had been
      barely control by infusion of human atrial natriuretic peptide (hANP). Coronary
      angiography revealed double vessel disease( #2 100%, #6 90).We performed coronary
      artery bypass grafting(CABG) with intraoperative cardiac resynchronization
      therapy. The heart failure was dramatically improved and the patient was
      discharged on foot 32 days after operation. However, careful observation of
      cardiac function is vital because of the possibility of progression to heart
      failure of NCLV.

PMID- 24322315
TI  - [Successful surgical treatment for catamenial pneumothorax at the time of
      menstruation].
AB  - A 39-year-old female was referred to our hospital due to repeated right
      pneumothorax. Each episode was related to the onset of menstruation, suggesting
      catamenial pneumothorax. Thoracoscopy showed multiple blue berry spots on the
      diaphragm. Partial resection of the diaphragm including these lesions were
      performed. But she had a recurrent right pneumothorax. Treatment with a
      gonadotropin-releasing hormone analogue was started, resulting in failure to
      introduce menopose and the pneumothorax repeatedly appeared again. Reoperation
      was intentionally done at the time of menstruation enable to find the lesion.
      Patient is free from pneumothorax more than 6 years after surgery.

PMID- 24322316
TI  - [Elderly Bochdalek hernia found out by intestinal obstruction].
AB  - A 78-year-old man, who had been pointed out elevation of the diaphragm by chest
      radiography, visited local physician complaining of abdominal pain and vomiting.
      He was referred to our hospital and was diagnosed as intestinal obstruction. The
      patient had neither respiratory symptoms nor findings of peritonitis. The
      radiography revealed intestinal gas with neveau formation in the left thorax. The
      computed tomography showed dilatation of the stomach and small intestine, and a
      diaphragmatic hernia was suspected. Although conservative treatment was started,
      radiographic and laboratory findings got worse on the 5th hospital day. The
      patient underwent surgery for a left diaphragmatic hernia with the intestinal
      obstruction. Diagnosis of Bochdalek hernia with hernia sac was established. The
      content of hernia was the perforated small intestine. Postoperative course was
      almost uneventful, and the patient was discharged on the 35th postoperative day
      without pyothorax. In treatment of adult Bochdalek hernia, early surgery is
      important because patients with incarceration or perforation often experience
      severe postoperative complication. 

PMID- 24322317
TI  - [Circulatory disturbance of middle lobe by bending of lobar pedicle after right
      upper lobectomy].
AB  - A 66-year-old man was diagnosed as lung cancer. We performed right upper
      lobectomy and lymphnode dissection. On the 1st postoperative day, a chest
      radiograph showed an opacification in the right upper lung field. Computed
      tomography (CT) showed a stenosis of the middle lobe bronchus and infiltrative
      shadow of the middle lobe on the 3rd postoperative day. Fiber optic bronchoscopic
      examination also revealed a bend and stenosis of the middle lobe bronchus, but
      tortion was not demonstrated. On the 6th postoperative day, chest radiographic
      findings was worsened. Torsion of the middle lobe was suspected, and
      rethoracotomy was performed on the 7th postoperative day. The right middle lobe
      was not rotated, but the lobar pedicle bend toward cranial. The middle lobe was
      highly congested necessitating lobectomy. 

PMID- 24322318
TI  - [Video-assisted thoracoscopic implantation of left ventricular pacing
      lead;usefulness of CARTO system;report of a case].
AB  - A 70-year-old man, with a history of broad anterior myocardial infarction and
      repeated several hospitalizations due to heart failure, was referred to our
      institution for cardiac resynchronization therapy. However, as intravenous
      implantation of the left ventricular pacemaker lead was not possible, the patient
      underwent video-assisted thoracoscopic (VAT) implantation. We noted broad
      myocardial scarring and patent grafts, along with previously bypassed left
      internal thoracic artery( LITA)-left anterior descending artery (LAD) and right
      internal thoracic artery (RITA)-D1;thus, the area suitable for implantation of
      the left ventricule (LV) pacemaker was believed to be restricted. Therefore, we
      decided to determine the viable myocardial area by using CARTO system and
      identify the appropriate access port positions for the subsequent VAT surgery.
      After the LV pacemaker lead was implanted, the recorded pacing threshold was
      found to be <1.2 V at 0.5 ms. Thus, the CARTO system might be useful to
      preoperatively identify an area suitable for surgical implantation of a LV
      pacemaker lead in patients with ischemic cardiomyopathy.

PMID- 24322319
TI  - [Successful postoperative percutaneous cardiopulmonary support( PCPS) for the
      right-heart failure in a patient with recurrent mitral valve stenosis and a
      calcified left atrium; report of a case].
AB  - A 79-year-old female underwent open mitral commissurotomy and thrombectomy for
      mitral valve stenosis and thrombus in the left atrium 21 years ago. She was
      admitted for congestive heart failure because of recurrent mitral valve stenosis.
      Cardiac echocardiography showed severe mitral valve stenosis and the
      calcification of the left atrium wall. We performed mitral valve replacement and
      removal of thrombus calcification in the left atrium. Cardiopulmonary bypass was
      weaned successfully. In the intensive care unit, her blood pressure (BP) dropped,
      central venous pressure (CVP) increased, and urine volume decreased. Cardiac
      echocardiography revealed functional deterioration and dilatation of the right
      ventricle. As medical therapy was not effective, percutaneous cardiopulmonary
      support(PCPS)was established through the femoral artery and vein. Then her BP
      increased, CVP decreased, and the right ventricular function and the dilatation
      improved. PCPS was removed after 3 days, and the respirator on the 13th
      postoperative day. She moved out of the intensive care unit on the 24th
      postoperative day. 

PMID- 24322320
TI  - [Extended total arch replacement with coronary artery bypass grafting( CABG) via
      left thoracotomy;report of a case].
AB  - The operative procedure of extensive aortic aneurysm with ischemic coronary
      artery disease is controversial. We report a case of arch and descending thoracic
      aortic aneurysm replacement with coronary artery bypass grafting(CABG)via left
      thoracotomy. A 70-year-old man followed up by hepatic disease was diagnosed with
      expanding aortic thoracic aneurysm at the other hospital. He had admission to our
      hospital for surgical intervention. Computed tomography(CT)revealed arch and
      descending thoracic aortic aneurysm, and coronary arteriography (CAG) revealed #7
      90% and #13 75% stenosis. We performed arch and descending thoracic aortic
      aneurysm replacement with CABG via left thoracotomy. Replaced synthetic graft and
      bypass grafts were patent on the postoperative CT. He was discharged at 15th
      postoperative day with no morbidity.

PMID- 24322321
TI  - [Concomitant off-pump coronary artery bypass and left lower lobectomy for lung
      cancer;report of a case].
AB  - A 58-year-old man had an abnormal shadow in the left lower lobe on his computed
      tomography, and also had stenosis of the coronary arteries. Preoperative coronary
      angiography revealed severe stenosis of right coronary artery (RCA), left
      anterior descending artery (LAD), and left circumflex branch(LCx). The diagnosis
      of lung cancer was made by transbronchial lung biopsy. Initially, we scheduled to
      undergo surgery of both the heart and lung in 2stage operation. However, before
      surgery, the infection of cavity was caused by tumor growing, so we performed the
      surgery in 1stage operation. Off-pump coronary artery bypass and left lower
      lobectomy with lymph node dissection was concomitantly performed. The
      postoperative course was uneventful. He was discharged after confirming the
      patent bypass grafting on the 13th postoperative day. Histopathological diagnosis
      was squamous cell carcinoma without lymph node metastasis. Lung cancer and
      ischemic heart disease can be surgically treated simultaneously, benefitting
      selected patients. 

PMID- 24322322
TI  - [Thymic mucosa-associated lymphoid tissue (MALT) lymphoma developing during long
      term follow-up for Sjogren's syndrome and idiopathic thrombocytopenic
      purpura;report of a case].
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of lymphoma that
      arises in small CD20-positive lymphocytes. We encountered a case of thymic MALT
      lymphoma treated with surgical intervention during long-term follow-up for
      Sjogren's syndrome and idiopathic thrombocytopenic purpura (ITP). Although
      symptomatic remission of Sjogren's syndrome and ITP had already been achieved,
      the levels of anti-SSA and anti-SSB antibodies remained high. Chronic stimulation
      by these antibodies may contribute to the development of MALT lymphoma. A careful
      follow-up may be indicated for this case with a complex immunological background.

PMID- 24322323
TI  - [Paratracheal lymph node metastasis from papillary thyroid carcinoma presented as
      a middle mediastinal cyst;report of a case].
AB  - The majority of middle mediastinal cysts are benign diseases. However, some cases
      of middle mediastinal cysts are revealed to be malignant tumor. We herein report
      a case of a middle mediastinal cyst, which proved to be a right paratracheal
      lymph node metastasis from the thyroid papillary carcinoma. The patient was a 67
      year-old lady who had underwent thyroidectomy and regional lymph node dissection
      for papillary thyroid carcinoma 6 years before. Follow-up computed tomography
      revealed a growing cyst at the right-side of the intrathoracic trachea.
      Metastasis from thyroid cancer was suspected from her history. The right upper
      mediastinal lymphadenectomy through thoracoscopy was performed. Pathologically,
      the cyst was diagnosed as a metastasis from thyroid cancer, showing cystic
      change. 

PMID- 24322324
TI  - [Recurrence of inflammatory myofibroblastic tumor of chest wall after radical
      resection;report of a case].
AB  - A 61-year-old male presented with an asymptomatic left chest wall (the 7th rib)
      tumor detected by positron emission tomography(PET). The increase of tumor size
      was indicated by computed tomography(CT) scan and complete resection including
      the 6th to 8th rib was performed due to intraoperative rapid diagnosis as
      sarcoma. The diagnosis of inflammatory myofibroblastic tumor (IMT) was
      established by final pathological diagnosis. Three years later, he had a relapse
      of 2 tumors in left chest wall (the 9th, 10th rib), and surgical resection was
      performed without chest wall resection. Histological findings of a relapse tumor
      showed a large size tumor cell and a decrease in the number of plasma cell
      compared to the 1st tumor. These changes may be related to a clinical aggressive
      behavior.

PMID- 24322325
TI  - Sequencing of five left-right cerebral asymmetry genes in a cohort of
      schizophrenia and schizotypal disorder patients from Russia.
AB  - OBJECTIVE: Schizophrenia is a severe psychiatric disorder, affecting ~1% of the
      human population. The genetic contribution to schizophrenia is significant, but
      the genetics are complex and many aspects of brain functioning, from neural
      development to synapse structure, seem to be involved in the pathogenesis. A
      novel way to study the molecular causes of schizophrenia is to study the genetics
      of left-right (LR) brain asymmetry, the disease feature often observed in
      schizophrenic patients. METHODS: In this study, we analyzed by sequencing five
      candidate LR cerebral asymmetry genes in a cohort of 95 schizophrenia and
      schizotypal disorder patients from Saint Petersburg, Russia. The gene list
      included LMO4, LRRTM1, FOXP2, the PCDH11X/Y gene pair, and SRY. RESULTS: We found
      17 previously unreported variants in the genes LRRTM1, FOXP2, LMO4, and PCDH11X
      in the 3'-UTR and 5'-UTR. The variants might contribute toward an altered mRNA
      processing, which could lead to altered mRNA amounts in developing neurons of the
      brain and establishment of an incorrect LR asymmetry profile. CONCLUSION: This is
      the first study in which multiple candidate genes for cerebral LR asymmetry and
      schizophrenia have been analyzed by sequencing. The approach to study the
      genetics of schizophrenia from the perspective of an LR cerebral asymmetry
      disturbance deserves more attention.

PMID- 24322326
TI  - Control over experience? Magnitude of the attentional blink depends on meditative
      state.
AB  - The information processing capacity of the human mind is limited, as is evidenced
      by the so-called 'attentional-blink' deficit. This deficit is believed to result
      from competition between stimuli for limited attentional resources. We examined
      to what extent advanced meditators can manipulate their attentional state and
      control performance on an attentional blink task. We compared the magnitude of
      the attentional blink between states of focused attention meditation (in which
      one focuses tightly on an object) and states of open monitoring meditation (in
      which one is simply aware of whatever comes into experience) in a sample of
      experienced meditators. We found a smaller attentional blink during open
      monitoring compared to focused attention meditation due to reduced T1 capture. Of
      note, this effect was only found for very experienced meditators (on average
      10,704 h of experience). These data may suggest that very advanced practitioners
      can exert some control over their conscious experience.

PMID- 24322327
TI  - Collective behaviours: from biochemical kinetics to electronic circuits.
AB  - In this work we aim to highlight a close analogy between cooperative behaviors in
      chemical kinetics and cybernetics; this is realized by using a common language
      for their description, that is mean-field statistical mechanics. First, we
      perform a one-to-one mapping between paradigmatic behaviors in chemical kinetics
      (i.e., non-cooperative, cooperative, ultra-sensitive, anti-cooperative) and in
      mean-field statistical mechanics (i.e., paramagnetic, high and low temperature
      ferromagnetic, anti-ferromagnetic). Interestingly, the statistical mechanics
      approach allows a unified, broad theory for all scenarios and, in particular,
      Michaelis-Menten, Hill and Adair equations are consistently recovered. This
      framework is then tested against experimental biological data with an overall
      excellent agreement. One step forward, we consistently read the whole mapping
      from a cybernetic perspective, highlighting deep structural analogies between the
      above-mentioned kinetics and fundamental bricks in electronics (i.e. operational
      amplifiers, flashes, flip-flops), so to build a clear bridge linking biochemical
      kinetics and cybernetics. 

PMID- 24322328
TI  - Evaluation of the glutamine 27 glutamic acid polymorphism in the adrenoceptor
      beta2 surface gene on obesity and metabolic phenotypes in Taiwan.
AB  - BACKGROUND: The single-nucleotide polymorphism (SNP), rs1042714 or glutamine 27
      glutamic acid (Gln27Glu), in the adrenoceptor beta2 surface (ADRB2) gene has
      previously been examined for association with obesity with inconclusive results.
      The objective of this study was to determine whether the ADRB2 rs1042714 SNP
      could influence obesity and obesity-related metabolic traits in a Taiwanese
      population. METHODS: The ADRB2 rs1042714 SNP and obesity-related metabolic traits
      including blood pressure, total cholesterol, triglyceride, fasting glucose, waist
      circumference, and body mass index (BMI) were examined in 967 individuals with
      general health examinations. RESULTS: Our data revealed that the ADRB2 rs1042714
      SNP exhibited a significant association with obesity among the subjects (P =
      0.021). Furthermore, the carriers of the GG genotype had a significantly higher
      BMI than those with the CC genotype (26.0 +/- 5.6 vs 24.3 +/- 3.8 kg/m; P =
      0.009) and those with the CG genotype (26.0 +/- 5.6 vs 23.6 +/- 3.3 kg/m; P =
      0.001). We also found a nominal association with systolic blood pressure (P =
      0.058) and triglyceride (P = 0.055) levels in the ADRB2 rs1042714 SNP.
      CONCLUSIONS: Our study indicates that the ADRB2 rs1042714 SNP may contribute to
      the risk of obesity and predict obesity-related metabolic traits such as BMI,
      triglyceride, and systolic blood pressure in Taiwanese subjects.

PMID- 24322329
TI  - Role of genetic variation in the cannabinoid receptor gene (CNR1) (G1359A
      polymorphism) on weight loss and cardiovascular risk factors after liraglutide
      treatment in obese patients with diabetes mellitus type 2.
AB  - BACKGROUND: A polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene
      was reported as a common polymorphism (rs1049353) with potential implications in
      weight loss. We decide to investigate the role of this polymorphism on metabolic
      changes and weight loss secondary to treatment with liraglutide. METHODS: A
      population of 86 patients with diabetes mellitus type 2 and obesity, unable to
      achieve glycemic control (hemoglobine glycate A1c >7%) with metformin alone or
      associated to sulfonylurea, who require initiation of liraglutide treatment in
      progressive dose to 1.8 mg/d subcutaneously, was analyzed. RESULTS: Fifty-one
      patients (59.3%) had the genotype G1359G, and 35 patients (40.7%) had G1359A (28
      patients, 32.6%) or A1359A (7 patients, 8.1%) (A allele carriers). In patients
      with both genotypes, basal glucose, HbA1c, body mass index, weight, fat mass,
      waist circumference, and systolic blood pressures decreased. In patients with
      G1359G genotype, total cholesterol and low-density lipoprotein cholesterol
      decreased, and in patients with A allele, homeostasis model assessment for
      insulin resistance decreased, too. CONCLUSIONS: There is an association of the A
      allele with an improvement of insulin resistance secondary to weight loss after
      liraglutide treatment in obese patients with diabetes mellitus type 2.
      Noncarriers of A allele showed an improvement in cholesterol levels after weight
      loss.

PMID- 24322330
TI  - Tobacco smoke-induced immunologic changes may contribute to oral carcinogenesis.
AB  - OBJECTIVE: The objective of this study was to determine if tobacco smoke (TS), a
      risk factor for cancers of the aerodigestive tract, may contribute to oral
      carcinogenesis, in part, by suppressing local immunity. METHODS: Mice were placed
      in Plexiglas holders in which they breathed TS through the nose and mouth for 1
      hour daily for 21 days. Control mice breathed room air in the same manner. One
      day after the last exposure, mice were immunized by application of oxazolone to
      each buccal mucosa. Control mice were mock immunized by application of vehicle
      alone. Five days later, all mice were challenged on the ears with oxazolone, and
      24-hour ear swelling assessed as contact hypersensitivity. RESULTS: Mice exposed
      to TS had a significantly smaller contact hypersensitivity response compared with
      controls. When subsequently reimmunized on the glabrous skin, mice originally
      primed through TS-exposed mucosa could not be fully immunized, indicating
      induction of immunologic tolerance by exposure to hapten through TS-perturbed
      mucosa. Immunocompetent mice exposed to TS in this manner and challenged by
      submucosal placement of a syngeneic malignant tumor had significantly increased
      tumor growth over time compared with controls. No difference in growth rate was
      observed when the experiment was performed with natural killer cell-deficient,
      SCID (severe combined immunodeficiency) mice. In addition, exposure of epidermal
      Langerhans cells in vitro to an aqueous extract of TS impaired their ability to
      undergo maturation and to present antigen to responsive T cells. CONCLUSIONS:
      Immunologic changes induced in the oral cavity by exposure to TS may play a role
      in the development of oral cancers.

PMID- 24322331
TI  - Therapeutic evaluation of Epstein-Barr virus-encoded latent membrane protein-1
      targeted DNAzyme for treating of nasopharyngeal carcinomas.
AB  - The ability of the 10-23 DNAzyme to specifically cleave RNA with high efficiency
      has fuelled expectation that this agent may have useful applications for targeted
      therapy. Here, we, for the first time, investigated the antitumor and
      radiosensitizing effects of a DNAzyme (DZ1) targeted to the Epstein-Barr virus
      (EBV)-LMP1 mRNA of nasopharyngeal carcinoma (NPC) in patients. Preclinical
      studies indicated that the DNAzyme was safe and well tolerated. A randomized and
      double-blind clinical study was conducted in 40 NPC patients who received DZ1 or
      saline intratumorally, in conjunction with radiation therapy. Tumor regression,
      patient survival, EBV DNA copy number and tumor microvascular permeability were
      assessed in a 3-month follow-up. The mean tumor regression rate at week 12 was
      significantly higher in DZ1 treated group than in the saline control group.
      Molecular imaging analysis showed that DZ1 impacted on tumor microvascular
      permeability as evidenced by a faster decline of the K(trans) in DZ1-treated
      patients. The percentage of the samples with undetectable level of EBV DNA copy
      in the DZ1 group was significantly higher than that in the control group. No
      adverse events that could be attributed to the DZ1 injection were observed in
      patients. 

PMID- 24322332
TI  - Intrathecal AAV serotype 9-mediated delivery of shRNA against TRPV1 attenuates
      thermal hyperalgesia in a mouse model of peripheral nerve injury.
AB  - Gene therapy for neuropathic pain requires efficient gene delivery to both
      central and peripheral nervous systems. We previously showed that an
      adenoassociated virus serotype 9 (AAV9) vector expressing short-hairpin RNA
      (shRNA) could suppress target molecule expression in the dorsal root ganglia
      (DRG) and spinal cord upon intrathecal injection. To evaluate the therapeutic
      potential of this approach, we constructed an AAV9 vector encoding shRNA against
      vanilloid receptor 1 (TRPV1), which is an important target gene for acute pain,
      but its role in chronic neuropathic pain remains unclear. We intrathecally
      injected it into the subarachnoid space at the upper lumbar spine of mice 3 weeks
      after spared nerve injury (SNI). Delivered shTRPV1 effectively suppressed mRNA
      and protein expression of TRPV1 in the DRG and spinal cord, and it attenuated
      nerve injury-induced thermal allodynia 10-28 days after treatment. Our study
      provides important evidence for the contribution of TRPV1 to thermal
      hypersensitivity in neuropathic pain and thus establishes intrathecal AAV9
      mediated gene delivery as an investigative and potentially therapeutic platform
      for the nervous system. 

PMID- 24322334
TI  - The dueling obligations of opioid stewardship.

PMID- 24322333
TI  - Maraba virus as a potent oncolytic vaccine vector.
AB  - The rhabdovirus Maraba has recently been characterized as a potent oncolytic
      virus. In the present study, we engineered an attenuated Maraba strain, defined
      as MG1, to express a melanoma-associated tumor antigen. Its ability to mount an
      antitumor immunity was evaluated in tumor-free and melanoma tumor-bearing mice.
      Alone, the MG1 vaccine appeared insufficient to prime detectable adaptive
      immunity against the tumor antigen. However, when used as a boosting vector in a
      heterologous prime-boost regimen, MG1 vaccine rapidly generated strong antigen
      specific T-cell immune responses. Once applied for treating syngeneic murine
      melanoma tumors, our oncolytic prime-boost vaccination protocol involving Maraba
      MG1 dramatically extended median survival and allowed complete remission in more
      than 20% of the animals treated. This work describes Maraba virus MG1 as a potent
      vaccine vector for cancer immunotherapy displaying both oncolytic activity and a
      remarkable ability to boost adaptive antitumor immunity. 

PMID- 24322335
TI  - Hemorrhagic radiation cystitis.
AB  - The optimal management of persistent hemorrhagic radiation cystitis is ill
      defined. Various options are available and include oral agents (ie, sodium
      pentosan polysulfate), intravenous drugs (ie, WF10), topical agents (ie,
      formalin), hyperbaric oxygen, and endoscopic procedures (ie, electrical cautery,
      argon plasma coagulation, laser coagulation). In general, it is best to manage
      patients conservatively and intervene only when necessary with the option least
      likely to exacerbate the cystitis. More aggressive measures should be employed
      only when more conservative approaches fail. Bladder biopsies should be avoided,
      unless findings suggest a bladder tumor, because they may precipitate a
      complication. 

PMID- 24322337
TI  - Extracorporeal membrane oxygenation in adult patients with acute respiratory
      distress syndrome.
AB  - PURPOSE OF REVIEW: To examine the role of extracorporeal membrane oxygenation
      (ECMO) as potential therapeutic option for severe cases of acute respiratory
      distress syndrome (ARDS). RECENT FINDINGS: The use of ECMO to treat acute
      respiratory failure dramatically increased. Factors that may explain this
      increase in the use of ECMO are H1N1 pandemic influenza, results of recent
      clinical trials and not lastly the technological development and consequently the
      commercial pressure of the industry. Under these circumstances, clinicians
      urgently need clinical trials and formal indication, contraindication and rules
      for implementation to provide reproducible results. SUMMARY: Guidelines from the
      Extracorporeal Life Support Organization still indicate ECMO for acute severe
      pulmonary failure potentially reversible and unresponsive to conventional
      management. The new definition of ARDS (Berlin definition) addresses clinicians
      to the best treatment options in respect of the severity of illness and allocates
      ECMO as a potential therapeutic option for patients with severe ARDS and a P/F
      ratio lower than 100 and proposed that the indication of ECMO may be shifted from
      the treatment of choice for refractory hypoxemia to the treatment of choice to
      minimize ventilator-induced lung injury.

PMID- 24322336
TI  - Phase I Study of Docetaxel Plus Nedaplatin in Patients With Metastatic or
      Recurrent Esophageal Squamous Cell Carcinoma After Cisplatin Plus 5-Fluorouracil
      Treatment.
AB  - OBJECTIVES: To date, no second-line chemotherapy regimen for esophageal squamous
      cell carcinoma (SCC) has been established. This clinical trial aimed to assess
      the optimum dose of docetaxel plus nedaplatin (cis-diammine-glycolate platinum)
      as second-line chemotherapy. METHODS: Patients with metastatic or recurrent
      esophageal SCC after treatment with cisplatin plus 5-fluorouracil received
      docetaxel (50 or 60 mg/m) plus nedaplatin (70 mg/m2) on day 1 every 4 weeks. The
      recommended dose was based on dose-limiting toxicities defined during the first
      cycle. RESULTS: From February 2009 to November 2011, 9 patients were enrolled in
      the study. Their median age was 62 years (range, 58 to 72 y). Six patients had
      undergone radiotherapy and 4 had undergone surgical resection of primary lesions.
      Dose-limiting toxicities were observed in 2 patients at dose level 1 (60 mg/m2
      docetaxel, 70 mg/m2 nedaplatin) but not at dose level 0 (50 mg/m2 docetaxel, 70
      mg/m nedaplatin). Thus, the maximum tolerated dose was established at dose level
      1. No severe nonhematological toxicity was observed. No patient achieved complete
      response, but 2 (22%; 95% confidence interval, 0%-49%) achieved partial response
      and 3 had stable disease. Median progression-free and overall survival times were
      2.1 and 9.5 months, respectively. CONCLUSIONS: Docetaxel plus nedaplatin
      chemotherapy seems to be a safe and feasible second-line regimen for the
      treatment of esophageal SCC. We recommend the administration of 50 mg/m2
      docetaxel (day 1) plus 70 mg/m2 nedaplatin (day 1) every 4 weeks in a phase II
      study.

PMID- 24322338
TI  - Dielectrophoretically-assisted electroporation using light-activated virtual
      microelectrodes for multiple DNA transfection.
AB  - Gene transfection is an important technology for various biological applications.
      The exogenous DNA is commonly delivered into cells by using a strong electrical
      field to form transient pores in cellular membranes. However, the high voltage
      required in this electroporation process may cause cell damage. In this study, a
      dielectrophoretically-assisted electroporation was developed by using light
      activated virtual microelectrodes in a new microfluidic platform. The DNA
      electrotransfection used a low applied voltage and an alternating current to
      enable electroporation and transfection. Single or triple fluorescence-carrying
      plasmids were effectively transfected into various types of mammalian cells, and
      the fluorescent proteins were successfully expressed in live transfected cells.
      Moreover, the multi-triangle optical pattern that was projected onto a
      photoconductive layer to generate localized non-uniform virtual electric fields
      was found to have high transfection efficiency. The developed
      dielectrophoretically-assisted electroporation platform may provide a simpler
      system for gene transfection and could be widely applied in many biotechnological
      fields. 

PMID- 24322339
TI  - An MR-compatible stereoscopic in-room 3D display for MR-guided interventions.
AB  - BACKGROUND AND METHODS: A commercial three-dimensional (3D) monitor was modified
      for use inside the scanner room to provide stereoscopic real-time visualization
      during magnetic resonance (MR)-guided interventions, and tested in a catheter
      tracking phantom experiment at 1.5 T. Brightness, uniformity, radio frequency
      (RF) emissions and MR image interferences were measured. RESULTS AND DISCUSSION:
      Due to modifications, the center luminance of the 3D monitor was reduced by 14%,
      and the addition of a Faraday shield further reduced the remaining luminance by
      31%. RF emissions could be effectively shielded; only a minor signal-to-noise
      ratio (SNR) decrease of 4.6% was observed during imaging. During the tracking
      experiment, the 3D orientation of the catheter and vessel structures in the
      phantom could be visualized stereoscopically.

PMID- 24322340
TI  - Long-term stem cell labeling by collagen-functionalized single-walled carbon
      nanotubes.
AB  - The monitoring of grafted stem cells is crucial to assess the efficiency,
      effectiveness and safety of such stem cell-based therapies. In this regard, a
      reliable and cytocompatible labeling method for stem cells is critically needed.
      In this study, the collagen-functionalized single-walled carbon nanotubes (Col
      SWCNTs) were used as imaging probes for labeling of human mesenchymal stem cells
      (hMSCs) and the inherent Raman scattering of SWCNTs was used to image the SWCNT
      labeled cells. The results showed that the Col-SWCNTs exhibit efficient cellular
      internalization by hMSCs without affecting their proliferation and
      differentiation. The prolonged dwell time of Col-SWCNTs in cells ensured the long
      term labeling for up to 2 weeks. This work reveals the potential of Col-SWCNTs as
      probes for long-term stem cell labeling. 

PMID- 24322341
TI  - Spontaneous splenic rupture in a patient with acute promyelocytic leukaemia
      during induction chemotherapy.
AB  - BACKGROUND: Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid
      leukaemia with high curability rates. However, it is often accompanied by severe
      coagulopathy and bleeding risk and thus represents a potentially fatal
      haematological emergency requiring immediate treatment. Spontaneous splenic
      rupture is a rare event in all haematological malignancies. Only two clinical
      cases have been described so far in a setting of APL. CASE REPORT: We report a
      patient with APL without preceding splenomegaly who underwent urgent splenectomy
      for spontaneously occurring splenic rupture during induction chemotherapy. After
      surgery the patient completed induction chemotherapy and achieved complete
      remission. CONCLUSION: This is the second case of spontaneous splenic rupture
      without preceding splenomegaly in a patient with APL during induction
      chemotherapy described so far. Our case demonstrates that emergent splenectomy
      can be lifesaving even in the unfavourable condition of patient with severe
      immune deficiency.

PMID- 24322342
TI  - Evaluation of biochemical markers and bone mineral density in patients with
      chronic kidney disease stage 5D at the start of hemodialysis treatment.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) have significant disorders
      of bone and mineral metabolism. In addition, they can also develop other bone
      disorders including osteoporosis. This study evaluated the bone mineral density
      (BMD) of patients at the start of hemodialysis treatment as well as the
      relationship between BMD and possible risk factors or biochemical markers.
      METHODS: The study was performed in 82 patients (28 females, 54 males). BMD was
      measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and the
      proximal femur. RESULTS: We found a high prevalence of 25-hydroxyvitamin D
      deficiency (96%; mean levels 30.0 +/- 17.7 nmol/L) and a reduction of BMD in
      comparison with gender- and age-matched normal population values at the total hip
      (Z-score = -0.31 +/- 1.11) and the femoral neck (Z-score = -0.48 +/- 1.16), but
      not at the lumbar spine (Z-score = 0.68 +/- 1.81). The prevalence of T-scores <= 
      2.5 SD in the group of patients over 50 years was 52.0% in females and 33.3% in
      males. BMD positively correlated: with male gender and calcium levels at all
      measured sites, with age at the lumbar spine and with weight or BMI at the
      proximal femur. CONCLUSION: CKD patients at the start of hemodialysis treatment
      had a high prevalence of low T-score values, corresponding to values for
      osteoporosis in the general population. BMD at the proximal femur was below the
      expected average for age and gender, but at the lumbar spine, BMD in hemodialysis
      patients was above average in persons without known CKD.

PMID- 24322343
TI  - Re-operation of idiopathic macular hole after failed initial surgery.
AB  - BACKGROUND: Persistent idiopathic macular hole (IMH) after initial pars plana
      vitrectomy (PPV) appears in approx. 12% of cases. It is, therefore, one of the
      most common complications. IMH re-operation results tend to be better in eyes
      where IMH had been closed, while IMH re-operations in cases when the initial
      surgery had failed tend to be less successful: IMH often becomes even larger and
      visual acuity decreases, anatomical success rate of closure is about 60% and the
      resulting postoperative visual acuity is about 20/100. AIMS: To establish
      anatomical and functional success rate of repeated operations of recurrent
      idiopathic macular hole. MATERIALS AND METHODS: We evaluated the retrospective
      results of re-operations of persisting IMH that is cases in which the initial
      surgery did not result in closure: 6 eyes in 6 patients out of the overall 55
      operated on IMH (primary PPV failed in almost 11% of cases). The follow-up period
      was 18 months (since the first surgery). RESULTS AND CONCLUSION: After the second
      PPV, the IMH was closed in 100% of operated eyes. It was not necessary to perform
      a third PPV during the follow-up period. In all cases the visual acuity improved.
      Anatomical and functional results of IMH treatment can be considered
      satisfactory. We consider the following combination of factors significant for
      the anatomical success rate of PPV: IMH size and stage, technical precision of
      the ILM peeling and the suction of the IMH contents, strict adherence to the
      recommended head positioning in early postoperative period, and IMH duration.

PMID- 24322344
TI  - A comparative cytogenetic study of miscarriages after IVF and natural conception
      in women aged under and over 35 years.
AB  - PURPOSE: To compare the frequency and the spectrum of karyotype abnormality in
      the first trimester miscarriages in women aged under and over 35 years, who
      conceived naturally (NC) and who conceived through in vitro fertilization (IVF).
      METHODS: Comparative analysis of cytogenetic data obtained by karyotyping of
      miscarriages in patients who conceived naturally, and who conceived through IVF.
      Patients were subcategorized by their age: <35 years (NC, n = 173; IVF, n = 108)
      and >= 35 years (NC, n = 107; IVF, n = 111). RESULTS: A total of 499 miscarriage
      karyotypes was analyzed. The spectrum and the relative proportions of different
      cytogenetic categories in karyotypically abnormal miscarriages differed neither
      between the NC and IVF patients aged <35 years, nor between the NC and IVF
      patients aged >= 35 years. In the patients aged <35 years, the incidence of
      abnormal miscarriage karyotype was lower in the IVF group (37.04 % vs 62.43%). In
      the patients aged >= 35 years, the incidence of miscarriages with cytogenetic
      pathology did not differ between the NC and the IVF group (75.70 % vs 58.56%).
      The lowest frequency of karyotypically abnormal miscarriages (29.82%) was
      detected in the young IVF-treated patients at <7 weeks of gestation. CONCLUSIONS:
      IVF does not increase the risk of a pregnancy loss because of abnormal embryonic
      karyotype, nor does it increase the preponderance for any specific type of
      cytogenetic abnormality in both patients aged under and over 35 years. In young
      IVF-treated women early pregnancy loss is generally caused by non-cytogenetic
      factors. Identification of a cytogenetically normal spontaneous abortion is
      clinically significant and reinforces the importance of developing an appropriate
      diagnosis and treatment strategies for IVF patients in order to reduce the risk
      of euploid pregnancy loss.

PMID- 24322345
TI  - The association of arylendosulfatase 1 (SULF1) gene polymorphism with recurrent
      miscarriage.
AB  - PURPOSE: One of the most common problems in reproductive medicine is recurrent
      miscarriage (RM). There is increasing evidence showing genetic susceptibility of
      women is an important risk factor in the occurrence of RM. In recent years, there
      is a growing interest in sulfate and its role in fetal development. A novel
      mechanism of SULF1 has been demonstrated for modifying the activities of some
      growth factors and signalling molecules that have major roles during
      embryogenesis. The aim of present study was to evaluate the association of SULF1
      gene polymorphism (rs6990375 G > A) in Iranian patients with RM. METHODS: We
      established a case-control study of 200 Iranian women: 100 patients with the
      history of two or more RM as cases and 100 healthy women with at least two cases
      of successful pregnancy and no history of miscarriage as controls. The
      polymorphism was examined by polymerase chain reaction restriction fragment
      length polymorphism (PCR-RFLP) method. RESULTS: The genotypic analysis between
      case and controls showed significant differences (p-value = 0.000). Allelic
      analysis showed no significant correlation (Chi2 = 3.36, p-value = 0.066). The
      heterozygous genetic variant was significantly higher among healthy women (OR =
      12.67, 95% CI = 6.47-24.79). CONCLUSIONS: Our data showed that rs6990375
      polymorphism of SULF1 gene could be among one of the factors related to RM in
      Iranian women. Further evaluation of this polymorphism may be important and need
      further studies.

PMID- 24322346
TI  - Molecular basis and evolutionary pattern of GA-GID1-DELLA regulatory module.
AB  - The tetracyclic diterpenoid carboxylic acids, gibberellins (GAs), orchestrate a
      broad spectrum of biological programs. In nature, GAs or GA-like substance is
      produced in bacteria, fungi, and plants. The function of GAs in microorganisms
      remains largely unknown. Phytohormones GAs mediate diverse growth and
      developmental processes through the life cycle of plants. The GA biosynthetic and
      metabolic pathways in bacteria, fungi, and plants are remarkably divergent. In
      vascular plants, phytohormone GA, receptor GID1, and repressor DELLA shape the GA
      GID1-DELLA module in GA signaling cascade. Sequence reshuffling, functional
      divergence, and adaptive selection are main driving forces during the evolution
      of GA pathway components. The GA-GID1-DELLA complex interacts with second
      messengers and other plant hormones to integrate environmental and endogenous
      cues, which is beneficial to phytohormones homeostasis and other biological
      events. In this review, we first briefly describe GA metabolism pathway,
      signaling perception, and its second messengers. Then, we examine the evolution
      of GA pathway genes. Finally, we focus on reviewing the crosstalk between GA-GID1
      DELLA module and phytohormones. Deciphering mechanisms underlying plant hormonal
      interactions are not only beneficial to addressing basic biological questions,
      but also have practical implications for developing crops with ideotypes to meet
      the future demand.

PMID- 24322347
TI  - Age distribution patterns of human gene families: divergent for Gene Ontology
      categories and concordant between different subcellular localizations.
AB  - The age distribution of gene duplication events within the human genome exhibits
      two waves of duplications along with an ancient component. However, because of
      functional constraint differences, genes in different functional categories might
      show dissimilar retention patterns after duplication. It is known that genes in
      some functional categories are highly duplicated in the early stage of vertebrate
      evolution. However, the correlations of the age distribution pattern of gene
      duplication between the different functional categories are still unknown. To
      investigate this issue, we developed a robust pipeline to date the gene
      duplication events in the human genome. We successfully estimated about three
      quarters of the duplication events within the human genome, along with the age
      distribution pattern in each Gene Ontology (GO) slim category. We found that some
      GO slim categories show different distribution patterns when compared to the
      whole genome. Further hierarchical clustering of the GO slim functional
      categories enabled grouping into two main clusters. We found that human genes
      located in the duplicated copy number variant regions, whose duplicate genes have
      not been fixed in the human population, were mainly enriched in the groups with a
      high proportion of recently duplicated genes. Moreover, we used a phylogenetic
      tree-based method to date the age of duplications in three signaling-related gene
      superfamilies: transcription factors, protein kinases and G-protein coupled
      receptors. These superfamilies were expressed in different subcellular
      localizations. They showed a similar age distribution as the signaling-related GO
      slim categories. We also compared the differences between the age distributions
      of gene duplications in multiple subcellular localizations. We found that the
      distribution patterns of the major subcellular localizations were similar to that
      of the whole genome. This study revealed the whole picture of the evolution
      patterns of gene functional categories in the human genome. 

PMID- 24322348
TI  - The effects of elastic fiber protein insufficiency and treatment on the modulus
      of arterial smooth muscle cells.
AB  - Elastic fibers are critical for the mechanical function of the large arteries.
      Mechanical effects of elastic fiber protein deficiency have been investigated in
      whole arteries, but not in isolated smooth muscle cells (SMCs). The elastic
      moduli of SMCs from elastin (Eln-/-) and fibulin-4 (Fbln4-/-) knockout mice were
      measured using atomic force microscopy. Compared to control SMCs, the modulus of
      Eln-/- SMCs is reduced by 40%, but is unchanged in Fbln4-/- SMCs. The Eln-/- SMC
      modulus is rescued by soluble or alpha elastin treatment. Altered gene
      expression, specifically of calponin, suggests that SMC phenotypic modulation may
      be responsible for the modulus changes. 

PMID- 24322349
TI  - [Can local administration of tranexamic acid reduce aspirin-induced bleeding in
      off-pump coronary artery bypass grafting( CABG) ?].
AB  - OBJECTIVES: We examined the effect of local administration of tranexamic acid(
      TA) on reducing aspirin-induced bleeding in off-pump coronary artery bypass
      grafting(CABG). METHODS: From July 2009 to January 2011, 88 cases with off-pump
      CABG were divided into 4 groups:group C including 19 cases without preoperative
      aspirin or local administration of TA, group A including 23 cases with
      preoperative aspirin alone, group T including 19 cases with local administration
      of TA alone, and group AT including 27 cases with both preoperative aspirin and
      local administration of TA. RESULTS: The bleeding volume after 24 hours in group
      A was significantly larger than that in group C(p=0.0085). The bleeding volume in
      group AT was significantly smaller than that in group A (p<0.0001), and the
      bleeding volume in group T was also significantly smaller than that in group C
      (p=0.0054). There was no significant difference between group T and AT.
      CONCLUSIONS: The use of local administration of tranexamic acid indicated the
      reduction of postoperative bleeding even in patients with preoperative aspirin
      use.

PMID- 24322350
TI  - [Examination of the postoperative change of pedicled pericardial fat pad for
      reinforcement of bronchial sutures by computed tomography].
AB  - A pedicled pericardial fat pad (PPFP) is often used in pulmonary resection to
      reinforce bronchial sutures. Here, we assessed the significance of PPFP by serial
      chest computed tomography (CT). Ten cases in which bronchial stump were covered
      with a PPFP in the past 6 years were reviewed. The procedures were pneumonectomy
      (3), lobectomy (6), and a segmentectomy. According to the CT value evaluated
      serially PPFP was recognized as fat tissue until 1~2 postoperative months. No
      cases of bronchopleural fistulae was encountered in this series. The coverage of
      the sutures with the PPFP was thought to contribute to the prevention of
      bronchial fistula by staying around bronchial stump for at least 1 to 2 months. 

PMID- 24322351
TI  - [Apico-aortic valved conduit for aortic stenosis in patients who could not
      tolerate median sternotomy].
AB  - This report presents 3 cases treated with an apico-aortic valved conduit. Cases
      1, 2:A 67-year-old female patient and a 60-year-old male patient what had
      undergone coronary artery bypass grafting were admitted to our hospital for
      severe aortic stenosis. Computed tomography showed a severe calcified ascending
      aorta, and coronary angiography revealed patent bypass graft. Case 3:A 71-year
      old male patient that had esophagectomy with retrosternal colonic interposition
      for esophagus cancer after distal gastrectomy. In addition, he had experienced
      anterior mediastinal drainagic therapy for anastomotic leak. All 3 patients were
      treated by implantation of an apico-aortic valved conduit. Operation:This
      procedure was performed through the 5th intercostal space under a beating heart
      with cardiopulmonary bypass. RESULT: Postoperative courses were uneventful. All
      patients are still alive without procedure-related events. CONCLUSION: This
      surgical procedure can be an effective alternative when conventional aortic valve
      replacement cannot be performed for aortic stenosis patients.

PMID- 24322352
TI  - [Nutritional treatment for bronchopleural fistula-promising effect of arginine as
      a pharmaconutrient].
AB  - Pharmaconutrition, which is a supportive nutritional care of surgical patients,
      has been proven to shorten hospital stay, decrease the incidence of infection,
      and reduce hospital costs in selected groups of patients. Arginine, one of the
      most essential pharmaconutrients, has also been proven to enhance would healing
      process. In severely malnourished patients like bronchopleural fistula with
      resultant empyema, aggressive nutritional approach should be mandatory. And
      management of the fistula is also important in stabilizing the ongoing infection.
      Our hypothesis was that basic nutritional support enhanced with arginine would be
      effective in not only improving the general condition including nutritional
      status but also in healing the fistula. We report a case of major bronchopleural
      fistula in which arginine-supplemented diet as well as aggressive nutritional
      support could accelerate the postoperative recovery after open thoracic window,
      ultimately leading to the healing of the fistula. 

PMID- 24322353
TI  - [Pulmonary sclerosing hemangioma with lymph node metastasis].
AB  - Sclerosing hemangioma is unusual pulmonary tumor. During a routine care
      evaluation, an abnormal shadow was detected in the chest X-ray films of a 38-year
      old woman. Chest computed tomography scanning showed a nodule, 3.9 cm in
      diameter, in the left S6 pulmonary segment. Bronchoscopy performed before the
      operation could not establish the diagnosis. Since low-grade malignant tumor
      wassuggested by frozen section analysis at surgery, segmentectomy of left S6 and
      sampling of interlober lymph node were performed. The tumor was diagnosed as a
      plmonary sclerosing hemangioma. Metastatic leasion in the interlober lymph node
      was pathologically confirmed. 

PMID- 24322354
TI  - [Feasibility of the use of absorbable sutures for closure of the sternum in adult
      cardiac surgery].
AB  - Steel wires are commonly used to close median sternotomy during adult cardiac
      surgery. Disruption or infection of the sternum can occure in 0.3~8% of those
      patients. We report the use of absorbable sutures for the closure of sternotomy.
      Three figure of 8 ligations were made. Cranial side suture was placed through the
      sternal manubrium. Other sutures were placed through the intercostal
      spaces.Sutures were tied 6 or 7 times. Braided #2 polyglactin suture were used in
      a consecutive 150 patients. Looped (double) #1 monofilament polyglyconate sutures
      were used in a subsequent 150 patients. Both sutures with blunt needle are
      commercially available. None of the patients in either group required re
      exploration of the sternum for bleeding and tamponade, and none developed wound
      infections or mediastinitis. Five patients in the polyglactin group developed
      seroma and/or instability of the sternum after more than 2 postoperative weeks,
      but none required surgical refixation of the sternum. These 5 patients had
      diabetes, chronic renal failure, autoimmune disease and/or chronic lung diseases.
      None of the patients in the polyglyconate group developed any trouble in their
      sternum. We conclude that polyglyconate sutures demonstrate good potential for
      use in closure of the sternum. 

PMID- 24322355
TI  - [Clinical experience of the articulating needle-holder for completely video
      assisted thoracoscopic surgery].
AB  - The autonomy Laparo-angle needle holder is a flexible device which has several
      articulating parts facilitating some traditionally difficult way of suture
      passage. This device is often used for laparoscopic surgery, and there have been
      few reports for video-assisted thoracic surgery (VATS). We used this device for
      complete VATS lobectomy and segmentectomy, and it enables us to suture a bronchus
      with the optimal direction even in the deep surgical field on complete VATS
      lobectomy and segmentectomy. Although some training may be needed to freely
      manipulate this device, it can be useful for minimallyinvasive video-assisted
      thoracic surgery. 

PMID- 24322356
TI  - [Y-graft replacement with left renal artery reconstruction for acute aortic
      dissection type B].
AB  - A 56-year-old male was admitted to our hospital for acute type B aortic
      dissection. He received conservative therapy but follow-up computed tomography
      (CT) revealed a low-enhanced left kidney and severe stenosis of the left common
      iliac artery due to the expansion of the false lumen. Serum blood urea nitrogen
      (BUN) and creatinine increased and renovascular hypertension worsened with severe
      intermittent claudication of the left leg. We performed Y-graft replacement with
      reconstruction of the left renal artery. Postoperative CT showed a well-enhanced
      left kidney and no stenosis of the left common iliac artery. Intermittent
      claudication and renal dysfunction improved and his hypertension became
      controllable. He was discharged on the 17th postoperative day. 

PMID- 24322357
TI  - [Multiple lung metastases from cutaneous adenoid cystic carcinoma resected 21
      years before].
AB  - A 79-year-old woman whose cutaneous tumor had been resected 21 years and 12 years
      (local recurrence)before pathologically confirmed as primary cutaneous adenoid
      cystic carcinoma (ACC), was referred to our hospital for the abnormal shadow on
      chest X-ray. Chest computed tomography (CT)revealed 3 nodules in the peripheral
      field of both lungs, which were diagnosed by echo-guided needle biopsy as
      metastasis from the cutaneous ACC, and were completely resected at 5 months
      intervals. Any recurrences have not been detected for 2 years after the lung
      resection. In primary cutaneous ACC, not only complete resection with adequate
      margin but long-term follow up is recommended. 

PMID- 24322358
TI  - [Fibrosing mediastinitis diagnosed by thoracoscopic biopsy].
AB  - We report a rare case of fibrosing mediastinitis diagnosed by thoracoscopic
      biopsy. A 56-year-old female visited our hospital with an abnormal mediastinal
      shadow on chest X ray. Chest computed tomography revealed a paravertebral tumor
      from Th9 to Th11. Pathological examination of thoracoscopic biopsy specimen
      showed fibrous tissue with mild inflammation and no malignant feature. Final
      diagnosis was idiopathic fibrosing mediastinitis. The paravertebral lesion
      shrinked spontaneously 5 months later after biopsy. 

PMID- 24322359
TI  - [Primary pulmonary malignant melanoma].
AB  - The patients was 63-year-old man. He had a chest abnormally shadow pointed out in
      examination of March, 2012 and referred to our hospital for a close inspection.
      The chest computed tomography(CT)revealed a mass shadow of 60 mm in left lung.
      Bronchoscopic examination was done and it was diagnosed as non-small-cell lung
      cancer by cytology. The clinical stage was cT2bN1M0 and video-assistedthoracic
      surgery (VATS) left pneumonectomy with mediastinal lymph node dissection was
      performed. A lot of neoplastic cells which contained melanin in cytoplasm were
      recognized by pathology and the diagnosis of malignant melanoma was comfirmed.
      Lymph node metastasis were recognized in #10, #11, #12 and the pathological stage
      of a disease was pT2bN1M0, pStage IIB. Further examination to find another lesion
      after surgery was in vain suggesting primary site to be left lung. A adjuvant
      chemotherapy has not been done. Surgical resection of primary pulmonary malignant
      melanoma is reported with reference to literatures. 

PMID- 24322360
TI  - [Open drainage with Vacuum Assisted Closure( VAC) therapy for Aspergillus empyema
      after left upper lobectomy with adjuvant radiotherapy].
AB  - A 59-year-old man was diagnosed as Aspergillus empyema with fistula after left
      upper lobectomy and radiation therapy. His pyrexia was continued after
      conservative treatment with antifungal agents. Initially, fenestration and vacuum
      assisted closure (VAC) therapy were performed. The Aspergillus terreusdisappeared
      and inflammatory reactions were normalized. Eight days after fenestration,
      pectoralis major muscle flap transposition was subsequently performed. His
      postoperative course was uneventful. No recurrent empyema was found 15 months
      after surgery. 

PMID- 24322361
TI  - [Aortic prosthetic valve endocarditis with aorto-left atrium fistula; report of a
      case].
AB  - An 83-year-old man had undergone aortic valve replacement (AVR)[CEP Magna 21 mm]
      and coronary aortic bypass grafting (CABG)[left internal thoracic artery (LITA)
      left anterier descending artery( LAD)] 2 years ago in our hospital. He was
      admitted for fever of unknown origin and developed a stroke to another hospital.
      The echocardiography and computerized tomography showed an abscessaround the
      aortic prosthetic valve. Prosthetic valve endocarditis (PVE) was diagnosed, and
      he was transferred to our hospital for surgical treatment. Three days after
      admission, acute heart failure developed that led to an emergency operation. When
      the ascending aorta was dissected, an aorto-left atrium fistula and vegetation
      were recognized. Aortic valve replacement and patch plasty of the aorto-left
      atrium fistula were performed successfully. This case was diagnosed as PVE with
      aorto-left atrium fistula, which is quite a rare complication of PVE. 

PMID- 24322362
TI  - [Primary left atrial myxofibrosarcoma; report of a case].
AB  - We herein report a very rare case of a primary left atrial myxofibrosarcoma. A 61
      year-old female presented with dyspnea and a wet cough. Chest X-ray film showed
      cardiomegaly and pulmonary congestion. Echocardiography and computed tomography
      revealed a left atrial tumor obstructing blood flow to the left ventricle. She
      was diagnosed with acute congestive heart failure due to functional
      mitralstenosis secondary to a left atrial tumor, and an emergency operation was
      performed. The tumor, which occupied left atrium, attached to the posterior wall
      of the left atrium and to the mitral valve, but had not invaded the left atrial
      wall. The tumor was removed from the left atrial wall, preserving the mitral
      valve and valve leaflets. The patient's post operative course was uneventful. The
      pathological diagnosis was myxofibrosarcoma, which rarely develops in the heart. 

PMID- 24322363
TI  - [Surgical repair for ascending aortic pseudoaneurysm derived from the proximal
      anastomotic site of saphenous vein graft after coronary artery bypass grafting;
      report of a case].
AB  - A 61-year-old male had undergone coronary artery bypass grafting (CABG) using a
      saphenous vein. Postoperative angiography represented an ascending aortic
      pseudoaneurysm derived from the proximal anastomotic site of the saphenous vein
      graft( SVG) which was connected to the obtuse marginal branch and left posterior
      descending branch sequentially. We performed the closure of tear and the
      plication of pseudoaneurysmal wall through median sternotomy on the 56th
      postoperative day. A 7mm length longitudinal tear in the ascending aorta close to
      the proximal anastomotic site of the SVG was observed. This tear was considered
      to be caused by the intimal injury during the anastomosis of SVG to ascending
      aorta. Aortic pseudoaneurysm formation close to the proximal anastomotic site of
      SVG is a rare and potentially lethal complication requiring urgent operation.
      Postoperative angiography or enhanced 3 dimensional computed tomography after
      CABG should be performed before hospital discharge. 

PMID- 24322364
TI  - [The surgical treatment using inverted graft insertion technique for left
      ventricular aneurysm combined with aortic stenosis; report of a case].
AB  - An 83-year-old female with congestive heart failure[ New York Heart
      Association(NYHA) classification III ] due to left ventricular aneurysm, aortic
      stenosis( AS) with an aortic valve area of 0.66 cm2 and moderate tricuspid
      regurgitation, underwent endoventricular circular patch plasty using inverted
      graft insertion technique, aortic valve replacement (AVR) and tricuspid
      annuloplasty (TAP) successfully. It is highly probable that moderate aortic
      stenosis and localized apical transmural infarction had been gradually getting
      worse and they coincidentally caused both progressed AS and ventricular
      aneurismal change in our case. 

PMID- 24322365
TI  - [Emergency surgery for coronary ostial occlusion and aortic root aneurysm
      associated with Takayasu's arteritis; report of a case].
AB  - We report a case of Takayasu's arteritis who underwent emergency surgery. A 39
      year-old female presented with severe back pain. Electrocardiogram demonstrated
      complete atrio-ventricular (AV) block and acute inferior myocardial infarction.
      Coronary angiography revealed ostial occlusion of the right coronary artery.
      Aortography and contrast-enhanced computed tomography revealed dilated and
      bizarre-shaped aortic root. The remainder of the aorta and its branches appeared
      normal. She underwent emergency aortic root replacement with valved conduit.
      Coronary artery bypass grafting to right coronary artery( RCA) using saphenous
      vein graft was performed concomitantly. Histologic findings of the aortic root
      were compatible with Takayasu's arteritis. Postoperative angiography showed graft
      patency. Takayasu arteritis should be considered for differential diagnosis of
      acute myocardial infarction in young woman. 

PMID- 24322366
TI  - [An ascending graft replacement surgery in acute aortic dissection with
      preoperative cerebral infarction responding to postoperative external and
      internal decompression; report of a case].
AB  - We report a case of a 71-year-old woman who had extensive cerebral infarction
      associated with acute type A aortic dissection. We urgently performed ascending
      aortic graft replacement. Postoperative computed tomography of the brain taken
      immediately after the aortic surgery showed further aggravation of the right
      cerebral edema and a midline shift. The patient underwent emergent internal and
      external decompression of the brain. Eventually, consciousness recovered to
      normal level though preoperative left paraplegia persisted. She was discharged
      150 days after the operation. We conclude that immediate internal and external
      cerebral decompression after surgery for acute type A dissection with
      preoperative cerebral malperfusion can prevent postoperative higher brain
      dysfunction. 

PMID- 24322367
TI  - Percutaneous cerclage wiring technique for phalangeal fractures.
AB  - Comminuted fractures of phalanx are challenging to reduce properly. Commonly, the
      fragments are distracted by various ligaments as well as flexor and extensor
      tendons. Splints, skeletal traction, Kirschner wire, plate and screws, and
      cerclage wires have all been used to manage such fractures. Among these, the
      cerclage wires are able to effectively contain the distracting forces and
      maintain a proper concentric reduction of the hollow tube structure of phalangeal
      bones. The resulting tissue-hardware construct is stable and allows early
      rehabilitation. Despite the obvious mechanical advantages, cerclage wiring of
      phalangeal fractures require open incisions. Inevitably, this approach leads to
      periosteal stripping, upon which the distracting forces exaggerate the
      displacement of comminuted fragments and the blood supply to the injured bone is
      compromised. To overcome the disadvantages of open approach, the authors have
      devised a minimally invasive technique in which the cerclage wire is introduced
      using a hypodermic needle for fractures of the proximal phalanx and distal
      phalanx base. 

PMID- 24322368
TI  - Processing strategies to obtain clean interleaved ultrafast 2D NMR spectra.
AB  - Ultrafast (UF) 2D NMR enables the acquisition of 2D spectra in a single-scan. In
      spite of its promising potential, the accessible spectral width is highly limited
      by the maximum gradient amplitude, which limits the general applicability of the
      method. A number of solutions have been recently described to deal with this
      limitation, among which stands the possibility to record several interleaved
      scans. However, this alternative acquisition scheme leads to numerous ghost peaks
      characteristic of interleaved acquisitions. These artefacts highly affect the
      readability of 2D spectra for structural elucidation, as well as their
      quantitative performance. Here, we propose several pre-FT or post-FT processing
      corrections to clean artefacts from interleaved ultrafast NMR spectra. Their
      performances are compared, and their potentialities are illustrated in a small
      organic molecule context. Post-FT processing corrections such as ArSub (Artefact
      Subtraction) or symmetrisation appear to be the most efficient ones in terms of
      artefact removal. While not purely single-scan, these strategies open new
      perspectives towards the routine use of UF 2D NMR for structural or quantitative
      analysis. 

PMID- 24322369
TI  - Fatty acids and epigenetics.
AB  - PURPOSE OF REVIEW: The purpose of this review is to assess the findings of recent
      studies on the effects of fatty acids on epigenetic process and the role of
      epigenetics in regulating fatty acid metabolism. RECENT FINDINGS: The DNA
      methylation status of the Fads2 promoter was increased in the liver of the
      offspring of mice fed an alpha-linolenic acid-enriched diet during pregnancy. In
      rats, increasing total maternal fat intake during pregnancy and lactation induced
      persistent hypermethylation of the Fads2 promoter in the liver and aortae of
      their offspring. However, increased fish oil intake in adult rats induced
      transient, reversible hypermethylation of Fads2. High-fat feeding in rodents also
      altered the levels of histone methylation in placentae and in adipose tissue.
      Dietary docosahexaenoic acid supplementation in pregnant women induced marginal
      changes in global DNA methylation in cord blood leukocytes. A high fat diet
      altered the DNA methylation status of specific genes in skeletal muscle in young
      men. SUMMARY: There are emerging findings that support the suggestion that fatty
      acids, in particular polyunsaturated fatty acids, can modify the epigenome.
      However, there is a need for rigorous investigations that assess directly the
      effect epigenetic modifications induced by fatty acids on gene function and
      metabolism.

PMID- 24322370
TI  - Influence of the Ba2+/Sr2+ content and oxygen vacancies on the stability of cubic
      Ba(x)Sr(1-x)Co(0.75)Fe(0.25)O(3-delta).
AB  - We present a theoretical and experimental study on the influence of the Ba/Sr and
      Co/Fe ratios as well as the oxygen-non-stoichiometry on the stability of
      Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF). Thin-layer depositions are analysed by
      looking at TEM images and EDX spectra. Bond-analytical calculations are performed
      to explain the stability difference between hexagonal and cubic BSCF. Finally,
      annealing experiments analysed using XRD give an insight into the differences of
      phase-fraction growth with respect to the Ba/Sr ratio. 

PMID- 24322371
TI  - Outcomes of a quality improvement project implementing stroke discharge advocacy
      to reduce 30-day readmission rates.
AB  - The purpose of this quality improvement project was to determine whether use of
      aspects of a transitional care model by nurse navigators would affect 30-day
      readmission rates in hospitalized ischemic stroke patients discharged home with
      self-care. Thirty-day readmission rates and emergency department (ED) visits were
      compared before, during, and after the implementation of the revised discharge
      process. Comparative analysis demonstrated reductions in readmissions and in ED
      visits. Thirty-day readmission rates to our hospital decreased from 9.39% to
      3.24% when comparing pre- with postintervention data. Thirty-day ED visit rates
      to all state hospitals decreased from 16.36% to 12.08% when comparing pre- with
      postintervention data. 

PMID- 24322373
TI  - In retrospect--a reflection on a 50-year research journey.
AB  - This essay is a personal review of a research journey extending over 50 years
      during which time the understanding of medical practice has changed out of all
      recognition and the quality and standing of the discipline of general practice
      has improved substantially. Three main bodies of work are reviewed and set
      against the reasons why they were undertaken. The first, on the pathology of the
      appendix and the management of possible appendicitis, was carried out almost
      entirely in the hospital setting. The second, about the prescribing of
      antibiotics for respiratory illnesses, and the third, about the determinants of
      good consulting practice, were carried out in general practice. The essay
      concludes with a reflection on the relevance of the work to some contemporary
      academic and health service issues. Although the work was carried out in the UK
      in the context of its National Health Service (NHS), the conclusions are widely
      generalizable and have contributed to health service and academic developments in
      many other countries. 

PMID- 24322372
TI  - Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic
      acid cycle of dendritic cell.
AB  - An imbalance of plasma amino acids (AA) is observed cirrhotic patients. Here we
      report that the imbalance suppresses the maturation of dendritic cells (DCs) by
      reducing the intracellular ATP due to interference with the mitochondrial
      tricarboxylic acid (TCA) cycle. We used serum-free culture medium consistent with
      the average concentration of the plasma AA from a healthy volunteer (HCM) and
      that from patients with advanced cirrhosis (ACM). We compared the function of DCs
      and the metabolism of glucose-amino acids under each medium. The maturation and
      intracellular ATP of immature DCs were lower under ACM in spite of the
      enhancement of mitochondrial respiratory chain complex genes. Metabolomics
      revealed that the TCA cycle metabolite, fumarate and 2-oxoglutarate were
      increased in DCs generated under ACM. Consistent with in vitro, In CD1c(+) or
      CD14(+) cells from cirrhotic patients, the gene expression of 2-oxoglutarate
      succinate-fumarate transition enzymes were significantly different from the cells
      of healthy controls. 

PMID- 24322374
TI  - Efficacy of concurrent chemoradiotherapy with 5-fluorouracil or gemcitabine in
      locally advanced biliary tract cancer.
AB  - PURPOSE: There is no established standard treatment for patients with locally
      advanced biliary tract cancer (BTC). METHODS: We analyzed the treatment results
      of locally advanced BTC from Jan 1995 to Dec 2010 at single institution of South
      Korea with retrospective study. One hundred and seventy-six patients were
      eligible to investigate the treatment response and toxicity. We treated these
      patients with 5-fluorouracil (5-FU)- or gemcitabine (GEM)-based concurrent
      chemoradiotherapy (CCRT) or best supportive care (BSC). The primary end point was
      overall survival. RESULTS: Of these locally advanced BTC patients, 106 patients
      received CCRT and 70 patients were treated with BSC. The median overall survival
      was 42.57 weeks (95 % confidence interval [CI], 35.85-49.30) in CCRT group and
      13.29 weeks (95 % CI 10.42-16.15) in BSC group (P < 0.001). Nausea and anemia
      were the most common toxicities observed. CONCLUSIONS: Patients with locally
      advanced BTC who were treated with 5-FU-based or GEM-based CCRT seem to have a
      better survival than those who received BSC. The treatment-related toxicity was
      mild. GEM-based or 5-FU-based CCRT showed similar survival advantages.

PMID- 24322375
TI  - Induction of DNA damage and p21-dependent senescence by Riccardin D is a novel
      mechanism contributing to its growth suppression in prostate cancer cells in
      vitro and in vivo.
AB  - PURPOSE: Our previous studies had shown that Riccardin D (RD) exhibited cytotoxic
      effects by induction of apoptosis and inhibition of angiogenesis and
      topoisomerase II. Here, we reported that apoptosis is not the sole mechanism by
      which RD inhibits tumor cell growth because low concentrations of RD caused
      cellular senescence in prostate cancer (PCa) cells. METHODS: Low concentrations
      of RD were used to treat PCa cells in vitro and in vivo, and senescence
      associated beta-galactosidase activity, DNA damage response markers, and/or
      colony-forming ability, cell cycle were analyzed, respectively. We then used
      siRNA knockdown to identify key factor in RD-triggered cellular senescence.
      RESULTS: RD treatment caused growth arrest at G0/G1 phase with features of
      cellular senescence phenotype such as enlarged and flattened morphology,
      increased senescence-associated-beta-galactosidase staining cells, and decreased
      cell proliferation in PCa cells. Induction of cellular senescence by RD occurred
      through activation of DNA damage response including increases in the phosphor
      H2AX, inactivation of Chk1/2, and suppression of repair-related Ku70/86 and
      phosphor-BRCA1 in PCa cells in vitro and in vivo. Analysis of expression levels
      of p53, p21(CIP1), p16(INK4a), p27(KIP1), pRb and E2F1 and genetic knockdown of
      p21(CIP1) demonstrated an important role of p21(CIP1) in RD-triggered cellular
      senescence. CONCLUSIONS: Involvement of the DNA damage response and p21(CIP1)
      defines a novel mechanism of RD action and indicates that RD could be further
      developed as a promising anticancer agent for cancer therapy.

PMID- 24322376
TI  - CA19-9 level as a prognostic and predictive factor of bevacizumab efficacy in
      metastatic colorectal cancer patients undergoing oxaliplatin-based chemotherapy.
AB  - PURPOSE: The prognostic and predictive values of carbohydrate antigen 19-9 (CA19
      9) levels in metastatic colorectal cancer (mCRC) remain unclear. We reviewed all
      mCRC patients at a single institution to evaluate the relationship between CA19-9
      levels and survival. METHODS: Two hundred and fifty-two patients underwent first
      line chemotherapy using oxaliplatin-based regimens between April 2005 and
      December 2009. The relationship between baseline CA19-9 levels and survival was
      analyzed. Moreover, we evaluated the relationship between baseline CA19-9 levels
      and clinicopathological factors. RESULTS: One hundred and fifty patients had
      elevated baseline CA19-9 levels (elevated group), and 79 patients had normal
      baseline CA19-9 (normal group) levels. Both KRAS and BRAF mutation rates were
      higher in the elevated group than in the normal group. Elevated CA19-9 level was
      a poor prognostic factor compared with normal CA19-9 levels (P = 0.0021). In the
      elevated group, the median survival time with bevacizumab was significantly
      longer with bevacizumab than without it (median OS, 27.8 vs. 15.3 months, P =
      0.0019). However, the median survival time was not different with or without
      bevacizumab in the normal group (median OS, 36.5 vs. 38.0 months, P = 0.9515).
      CONCLUSION: Our results suggest that baseline CA19-9 level is an independent
      prognostic factor in mCRC patients, and it correlated with the KRAS/BRAF mutation
      status. Bevacizumab exhibits clinical activity only for high CA19-9 levels in
      mCRC.

PMID- 24322377
TI  - Randomized controlled study of gemcitabine plus S-1 combination chemotherapy
      versus gemcitabine for unresectable pancreatic cancer.
AB  - PURPOSE: The aim of this study was to evaluate efficacy and safety of gemcitabine
      plus S-1 (GS) combination chemotherapy in patients with unresectable pancreatic
      cancer. METHODS: Patients were randomly assigned to receive GS (oral S-1 60
      mg/m(2) daily on days 1-15 every 3 weeks and gemcitabine 1,000 mg/m(2) on days 8
      and 15) or gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks). The
      primary endpoint was progression-free survival (PFS). RESULTS: One hundred and
      one patients were randomly assigned. PFS was significantly longer in the GS arm
      with an estimated hazard ratio (HR) of 0.65 (95 % CI 0.43-0.98; P = 0.039; median
      5.3 vs 3.8 months). Objective response rate (ORR) was also better in the GS arm
      (21.6 vs 6 %, P = 0.048). Median survival was 8.6 months for GS and 8.6 months
      for GEM (HR 0.93; 95 % CI 0.61-1.41; P = 0.714). Grade 3-4 neutropenia (44 vs
      19.6 %, P = 0.011) and thrombocytopenia (26 vs 8.7 %, P = 0.051) were more
      frequent in the GS arm. CONCLUSIONS: GS therapy improved PFS and ORR with
      acceptable toxicity profile in patients with unresectable pancreatic cancer.

PMID- 24322378
TI  - Results of a multicenter randomized controlled trial of the clinical
      effectiveness of schema therapy for personality disorders.
AB  - OBJECTIVE: The authors compared the effectiveness of 50 sessions of schema
      therapy with clarification-oriented psychotherapy and with treatment as usual
      among patients with cluster C, paranoid, histrionic, or narcissistic personality
      disorder. METHOD: A multicenter randomized controlled trial, with a single-blind
      parallel design, was conducted between 2006 and 2011 in 12 Dutch mental health
      institutes. A total of 323 patients with personality disorders were randomly
      assigned (schema therapy, N=147; treatment as usual, N=135; clarification
      oriented psychotherapy, N=41). There were two cohorts of schema therapy
      therapists, with the first trained primarily with lectures and the second
      primarily with exercises. The primary outcome was recovery from personality
      disorder 3 years after treatment started (assessed by blinded interviewers).
      Secondary outcomes were dropout rates and measures of personality disorder
      traits, depressive and anxiety disorders, general psychological complaints,
      general and social functioning, self-ideal discrepancy, and quality of life.
      RESULTS: A significantly greater proportion of patients recovered in schema
      therapy compared with treatment as usual and clarification-oriented
      psychotherapy. Second-cohort schema therapists had better results than first
      cohort therapists. Clarification-oriented psychotherapy and treatment as usual
      did not differ. Findings did not vary with specific personality disorder
      diagnosis. Dropout was lower in the schema therapy and clarification-oriented
      psychotherapy conditions. All treatments showed improvements on secondary
      outcomes. Schema therapy patients had less depressive disorder and higher general
      and social functioning at follow-up. While interview-based measures demonstrated
      significant differences between treatments, differences were not found with self
      report measures. CONCLUSIONS: Schema therapy was superior to treatment as usual
      on recovery, other interview-based outcomes, and dropout. Exercise-based schema
      therapy training was superior to lecture-based training.

PMID- 24322379
TI  - An integrated approach to realizing high-performance liquid-junction quantum dot
      sensitized solar cells.
AB  - Solution-processed semiconductor quantum dot solar cells offer a path towards
      both reduced fabrication cost and higher efficiency enabled by novel processes
      such as hot-electron extraction and carrier multiplication. Here we use a new
      class of low-cost, low-toxicity CuInSexS2-x quantum dots to demonstrate
      sensitized solar cells with certified efficiencies exceeding 5%. Among other
      material and device design improvements studied, use of a methanol-based
      polysulfide electrolyte results in a particularly dramatic enhancement in
      photocurrent and reduced series resistance. Despite the high vapour pressure of
      methanol, the solar cells are stable for months under ambient conditions, which
      is much longer than any previously reported quantum dot sensitized solar cell.
      This study demonstrates the large potential of CuInSexS2-x quantum dots as active
      materials for the realization of low-cost, robust and efficient photovoltaics as
      well as a platform for investigating various advanced concepts derived from the
      unique physics of the nanoscale size regime. 

PMID- 24322380
TI  - Furan fused V-shaped organic semiconducting materials with high emission and high
      mobility.
AB  - We report a facile synthetic protocol for preparation of dinaphtho[2,3-b:2',3'
      d]furan (DNF-V) derivatives. DNF-V derivatives showed high emissive behaviour in
      solid. A solution-crystallized transistor based on alkylated DNF-V derivatives
      showed an excellent carrier mobility of up to 1.3 cm(2) V(-1) s(-1), thereby
      proving to be a new solution-processable active organic semiconductor with high
      emission and high mobility. 

PMID- 24322381
TI  - The other genome: a systematic review of studies of mitochondrial DNA haplogroups
      and outcomes of HIV infection and antiretroviral therapy.
AB  - Mitochondrial toxicity is implicated in some treatment-limiting antiretroviral
      therapy complications, and reports of mitochondrial dysfunction in untreated HIV
      infection suggest antiretroviral therapy independent effects of HIV. Several
      studies have explored associations between mtDNA haplogroups (patterns of mtDNA
      polymorphisms) and outcomes of HIV infection and/or antiretroviral therapy, but
      findings have been inconsistent. We systematically reviewed published studies
      examining mtDNA haplogroups in HIV-infected persons to summarize reported outcome
      associations, and to highlight potential future research directions. We
      identified 21 articles published from 2005-2013. Multiple different phenotypes
      were studied; most were antiretroviral therapy associated metabolic outcomes
      (e.g. lipodystrophy, insulin resistance, and dyslipidemia). Haplogroup H was
      associated with the most outcomes, including AIDS progression, CD4 T-cell
      recovery, cirrhosis (in hepatitis C coinfection), and metabolic outcomes. This
      review is the first to focus on the emerging area of mtDNA haplogroups in HIV,
      and summarizes the published literature on associations between mtDNA haplogroups
      and clinical outcomes in populations of European and African descent. Several
      reported associations require replication and ideally biological verification
      before definitive conclusions can be drawn, but research in this area has the
      potential to explain outcome disparities and impact clinical management of
      patients. 

PMID- 24322383
TI  - Time to HIV-1 RNA suppression below 5 copies/ml during first-line protease
      inhibitor-based antiretroviral treatment - any impact of residual viremia on
      treatment success?
AB  - When antiretroviral treatment suppresses HIV RNA levels to below 50 copies/ml,
      traces of viremia may still be detected with more sensitive assays. In the
      ARTEMIS trial, 689 antiretroviral treatment-naive patients were randomized to
      tenofovir/emtricitabine plus either darunavir/ritonavir (n = 343) or
      lopinavir/ritonavir (n = 346). HIV-1 RNA was evaluated using the Roche
      Amplicor(r) Ultrasensitive assay: plasma samples with HIV RNA < 50 copies/ml were
      classified as either "No HIV RNA detected" (< 5 HIV RNA copies/ml, optical
      density = background) or HIV RNA detected (5-50 copies/ml). The percentage of
      patients in each arm with HIV RNA < 5 copies/ml rose progressively from week 2 to
      week 192. For patients with baseline HIV RNA >= 100,000, the percentage with HIV
      RNA < 5 copies/ml at week 192 was 66% for darunavir/ritonavir and 63% for
      lopinavir/ritonavir. For patients with baseline HIV RNA < 100,000 copies/ml, the
      percentage with HIV RNA < 5 copies/ml at week 192 was 79% for darunavir/ritonavir
      versus 77% for lopinavir/ritonavir. Of the patients on darunavir/ritonavir with
      HIV RNA < 50 copies/ml, 63% had levels < 5 copies/ml at week 48, versus 80% at
      week 192. In summary, HIV-1 RNA suppression to < 5 copies/ml is dependent on
      baseline HIV RNA levels. The HIV RNA levels can remain under quantification
      limits but still detectable after 2-4 years of antiretroviral treatment. 

PMID- 24322382
TI  - Implementing HIV-1 genotypic resistance testing in antiretroviral therapy
      programs in Africa: needs, opportunities, and challenges.
AB  - Tremendous progress has been made with the scale-up of antiretroviral therapy in
      Africa, with an estimated seven million people now receiving antiretroviral
      therapy in the region. The long-term success of antiretroviral therapy programs
      depends on appropriate strategies to deal with potential threats, one of which is
      the emergence and spread of antiretroviral drug resistance. Whilst public health
      surveillance forms the mainstay of the World Health Organization approach to
      antiretroviral drug resistance, there is likely to be increasing demand for
      access to drug resistance testing as programs mature and as HIV clinical
      management becomes more complex. African-owned research initiatives have helped
      to develop affordable resistance testing appropriate for use in the region, and
      have developed delivery models for resistance testing at different levels of the
      public health system. Some upper-middle-income countries such as Botswana and
      South Africa have introduced drug resistance testing for selected patient groups
      to guide clinical management. The scale-up of resistance testing will require
      substantial expansion of clinical and laboratory capacity in the region, but the
      expertise and resources exist in Africa to support this. The long-term population
      health impact and cost-effectiveness of resistance testing in the region will
      also require further investigation. 

PMID- 24322384
TI  - Cancer in HIV patients.
AB  - Starting antiretroviral therapy (ART) with low CD4 counts raises the likelihood
      of certain cancers, but others increase with longer time on therapy, reflecting
      the rising risk associated with older age. Researchers in the USA looked at
      patterns of cancer incidence and timing after ART initiation (Yanik, et al. Clin
      Infect Dis. 2013;57:756-64). The analysis included medical records from 11,485
      participants in eight U.S. HIV clinical cohorts who started ART between 1996 and
      2011. Around 80% were male and they started treatment at a median age of 38
      years. At the time of ART initiation, the median CD4 count was 202 cells/mm3.
      Nearly half started a protease inhibitor regimen. The authors looked at incidence
      rates for AIDS-defining cancers (Kaposi sarcoma [KS], non-Hodgkin's lymphoma, and
      cervical cancer) and non-AIDS cancers. They separately assessed cancers caused by
      viruses, such as hepatocellular carcinoma caused by hepatitis B or C, lymphoma
      related to Epstein-Barr virus, and cervical or anal cancer caused by human
      papillomavirus (HPV). 

PMID- 24322385
TI  - Once-daily raltegravir moving ahead.
AB  - Raltegravir is a highly potent antiretroviral agent, with arguably one of the
      most favorable adverse event profiles in the HIV armamentarium. However, its
      standard twice-daily (BID) dosing schedule makes it less convenient than once
      daily (QD) options. Although pharmacokinetic data suggest that QD raltegravir may
      provide adequate drug levels, the randomized phase III QDMRK trial (Eron, et al.
      Lancet Infect Dis. 2011;11:907-15) showed that 800 mg QD raltegravir failed to
      meet the criteria for non-inferiority when compared with 400 mg BID RAL in
      antiretroviral-naive HIV-infected individuals. 83% of patients in the QD arm
      achieved undetectable HIV viremia, in comparison with 89% in the BID arm. This
      was largely due to poorer efficacy among people with high baseline viral load (74
      vs. 84%, respectively). 

PMID- 24322387
TI  - [Medical ethics in the undergraduate medical curriculum and in the health care
      system].
AB  - In German speaking areas, in the scientific establishment which is occupied with
      medical ethics in the narrower and wider senses, a vehement discussion has
      developed as to whether or not medical practitioners must ultimately advocate
      that which is understood to be modern medical ethics. Against the background of
      this discussion, this article takes up a position on these questions, not only
      theoretically, but also with reference to the fields of practice of medical
      studies, hospitals, and the health system. The article presents the proposals of
      the Institute for Ethics and Law in Medicine (University of Vienna) for the
      evaluation and further development of the theme of ethics within the framework of
      the Medical Curriculum of Vienna (MCW). Among other things, this requires an
      integrated model of levels of ethical competence. 

PMID- 24322386
TI  - [What ethanol metabolites as biological markers tell us about alcohol use].
AB  - Alcohol and tobacco related disorders are the two leading and most expensive
      causes of illness in central Europe. In addition to self reports and
      questionnaires, biomarkers are of relevance in diagnosis and therapy of alcohol
      use disorders. Traditional biomarkers such as gamma glutamyl transpeptidase or
      mean corpuscular volume are indirect biomarkers and are subject to influence of
      age, gender and non alcohol related diseases, among others.Direct ethanol
      metabolites such as ethyl glucuronide (EtG), ethyl sulphate (EtS) and
      phosphatidylethanol (PEth) are direct metabolites of ethanol, that are positive
      after intake of ethyl alcohol. They represent useful diagnostic tools for
      identifying alcohol use even more accurately than traditional biomarkers. Each of
      these drinking indicators remains positive in serum and urine for a
      characteristic time spectrum after the cessation of ethanol intake--EtG and EtS
      in urine up to 7 days, EtG in hair for months after ethanol has left the body.
      Applications include clinical routine use, emergency room settings, proof of
      abstinence in alcohol rehabilitation programs, driving under influence offenders,
      workplace testing, assessment of alcohol intake in the context of liver
      transplantation and fetal alcohol syndrome.

PMID- 24322388
TI  - Intravesical instillations with polydeoxyribonucleotides reduce symptoms of
      radiation-induced cystitis in patients treated with radiotherapy for pelvic
      cancer: a pilot study.
AB  - PURPOSE: Chronic radiation cystitis (CRC) is a serious complication that can
      arise in patients with pelvic malignancies treated with radiotherapy.
      Polydeoxyribonucleotides (PDRNs) are known to reduce inflammation and improve
      tissue perfusion and angiogenesis. In this manuscript, we describe our
      observational experience regarding intravesical instillation of PDRNs in
      improving symptoms of CRC in subjects unresponsiveness to conventional medical
      therapy. METHODS: Eight patients with persistent and/or worsening CRC symptoms,
      despite conventional therapy, received biweekly intravesical instillation of
      PDRNs for two consecutive months. Symptoms were scored according to the Late
      Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA)
      scale, before, at the end, and after 4 months following the PDRNs treatment.
      RESULTS: Four months after instillations, a significant improvement in the
      subjective perception of CRC symptoms was experienced by participants. The mean
      LENT-SOMA score was reduced from 1.16+0.26 before to 0.34+0.035 after 4 months
      from instillations (p<0.001). No adverse effect related to instillations was
      reported. CONCLUSIONS: Subjective perception of persistent and/or worsening CRC
      symptoms, despite conventional therapy, is improved after intravesical
      instillation with PDRNs without adverse events. Even though we deduced suggestive
      insights, the results need to be collected and verified from a large-scale study.

PMID- 24322389
TI  - Combined QSAR and molecule docking studies on predicting P-glycoprotein
      inhibitors.
AB  - P-glycoprotein (P-gp) is an ATP-binding cassette multidrug transporter. The over
      expression of P-gp leads to the development of multidrug resistance (MDR), which
      is a major obstacle to effective treatment of cancer. Thus, designing effective P
      gp inhibitors has an extremely important role in the overcoming MDR. In this
      paper, both ligand-based quantitative structure-activity relationship (QSAR) and
      receptor-based molecular docking are used to predict P-gp inhibitors. The results
      show that each method achieves good prediction performance. According to the
      results of tenfold cross-validation, an optimal linear SVM model with only three
      descriptors is established on 857 training samples, of which the overall accuracy
      (Acc), sensitivity, specificity, and Matthews correlation coefficient are 0.840,
      0.873, 0.813, and 0.683, respectively. The SVM model is further validated by 418
      test samples with the overall Acc of 0.868. Based on a homology model of human P
      gp established, Surflex-dock is also performed to give binding free energy-based
      evaluations with the overall accuracies of 0.823 for the test set. Furthermore, a
      consensus evaluation is also performed by using these two methods. Both QSAR and
      molecular docking studies indicate that molecular volume, hydrophobicity and
      aromaticity are three dominant factors influencing the inhibitory activities.

PMID- 24322390
TI  - Sound-sensitive neurons innervate the ventro-lateral protocerebrum of the
      heliothine moth brain.
AB  - Many noctuid moth species perceive ultrasound via tympanic ears that are located
      at the metathorax. Whereas the neural processing of auditory information is well
      studied at the peripheral and first synaptic level, little is known about the
      features characterizing higher order sound-sensitive neurons in the moth brain.
      During intracellular recordings from the lateral protocerebrum in the brain of
      three noctuid moth species, Heliothis virescens, Helicoverpa armigera and
      Helicoverpa assulta, we found an assembly of neurons responding to transient
      sound pulses of broad bandwidth. The majority of the auditory neurons ascended
      from the ventral cord and ramified densely within the anterior region of the
      ventro-lateral protocerebrum. The physiological and morphological characteristics
      of these auditory neurons were similar. We detected one additional sound
      sensitive neuron, a brain interneuron with its soma positioned near the calyces
      of mushroom bodies and with numerous neuronal processes in the ventro-lateral
      protocerebrum. Mass-staining of ventral-cord neurons supported the assumption
      that the ventro-lateral region of the moth brain was the main target for the
      auditory projections ascending from the ventral cord. 

PMID- 24322391
TI  - cAMP with other signaling cues converges on Rac1 to stabilize the endothelial
      barrier- a signaling pathway compromised in inflammation.
AB  - cAMP is one of the most potent signaling molecules to stabilize the endothelial
      barrier, both under resting conditions as well as under challenge of barrier
      destabilizing mediators. The two main signaling axes downstream of cAMP are
      activation of protein kinase A (PKA) as well as engagement of exchange protein
      directly activated by cAMP (Epac) and its effector GTPase Rap1. Interestingly,
      both pathways activate GTP exchange factors for Rac1, such as Tiam1 and Vav2 and
      stabilize the endothelial barrier via Rac1-mediated enforcement of adherens
      junctions and strengthening of the cortical actin cytoskeleton. On the level of
      Rac1, cAMP signaling converges with other barrier-enhancing signaling cues
      induced by sphingosine-1-phosphate (S1P) and angiopoietin-1 (Ang1) rendering Rac1
      as an important signaling hub. Moreover, activation of Rap1 and inhibition of
      RhoA also contribute to barrier stabilization, emphasizing that regulation of
      small GTPases is a central mechanism in this context. The relevance of cAMP/Rac1
      mediated barrier protection under pathophysiologic conditions can be concluded
      from data showing that inflammatory mediators causing multi-organ failure in
      systemic inflammation or sepsis interfere with this signaling axis on the level
      of cAMP or Rac1. This is in line with the well-known efficacy of cAMP to abrogate
      the barrier breakdown in response to most barrier-compromising stimuli. New is
      the notion that the tight endothelial barrier under resting conditions is
      maintained by (1) continuous cAMP formation induced by hormones such as
      epinephrine or (2) by activation of Rac1 downstream of S1P that is secreted by
      erythrocytes and activated platelets. 

PMID- 24322392
TI  - Candidates for the light entrainment pathway to the circadian clock of the
      Madeira cockroach Rhyparobia maderae.
AB  - The circadian pacemaker controlling locomotor activity rhythms in the Madeira
      cockroach is located at the accessory medulla (AMe). The ipsi- and contralateral
      compound eyes provide light input to the AMe, possibly via the gamma-aminobutyric
      acid (GABA)-immunoreactive (-ir) distal tract, which connects the glomeruli of
      the AMe to the ipsilateral medulla and lamina. To identify possible light
      entrainment pathways, double-label immunocytochemistry was performed employing
      antibodies against GABA, myoinhibitory peptide (MIP), allatotropin (AT) and
      orcokinin (ORC). While all antisera tested, except the anti-ORC, prominently
      stained the glomeruli of the AMe, colocalization with anti-GABA was detected
      neither in the glomeruli nor in the distal tract. However, one median neuron that
      colocalized GABA-, AT- and MIP-immunoreactivity appeared to connect all glomeruli
      of the AMe to the medulla and lamina. Furthermore, one distal-frontoventral local
      neuron with arborizations in all glomeruli of the AMe colocalized anti-AT- and
      anti-MIP immunoreactivity. As candidates for contralateral light entrainment
      pathways, one ventromedian and one ventral neuron colocalized MIP- and ORC
      immunoreactivity, projecting via posterior and anterior commissures. Both
      branched in the interglomerular region of the AMe, where arborizations co-labeled
      with anti-ORC- and anti-MIP antisera. A possible role for MIP in light
      entrainment is supported also by injections of Rhyparobia maderae-specific MIP-2,
      which generated an all-advance phase-response curve late at night. Future
      experiments will challenge our hypothesis that GABA-, MIP- and AT-ir neurons
      provide ipsilateral light entrainment to all glomeruli, while MIP- and ORC-ir
      neurons carry contralateral light entrainment to the AMe's interglomerular
      region, either delaying or advancing AMe neurons light-dependently. 

PMID- 24322393
TI  - Multi-spectroscopic and molecular modeling studies on the interaction of
      antihypertensive drug; methyldopa with calf thymus DNA.
AB  - The interaction of methyldopa [(S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl
      propanoic acid] (MDP), antihypertensive drug, with calf thymus DNA (ct-DNA) was
      investigated by spectroscopic and viscometric techniques. According to the
      results arising from the fluorescence spectra, viscosity measurements and
      molecular modeling studies; we concluded that MDP is a minor groove binder of ct
      DNA and preferentially binds to AT rich regions. Ethidium bromide (EB)
      displacement studies revealed that MDP did not have any effect on EB bound DNA
      which is indicative of groove binding. This was substantiated by displacement
      studies with Hoechst 33258, a known minor groove binder. In addition, the
      thermodynamic and docking parameters showed that hydrophobic interaction via drug
      aromatic rings inside the DNA minor groove plays a major role in this binding. 

PMID- 24322394
TI  - Spatial distribution of cosmetic-procedure businesses in two U.S. cities: a pilot
      mapping and validation study.
AB  - Cosmetic procedures have proliferated rapidly over the past few decades, with
      over $11 billion spent on cosmetic surgeries and other minimally invasive
      procedures and another $2.9 billion spent on U.V. indoor tanning in 2012 in the
      United States alone. While research interest is increasing in tandem with the
      growth of the industry, methods have yet to be developed to identify and
      geographically locate the myriad types of businesses purveying cosmetic
      procedures. Geographic location of cosmetic-procedure businesses is a critical
      element in understanding the public health impact of this industry; however no
      studies we are aware of have developed valid and feasible methods for spatial
      analyses of these types of businesses. The aim of this pilot validation study was
      to establish the feasibility of identifying businesses offering surgical and
      minimally invasive cosmetic procedures and to characterize the spatial
      distribution of these businesses. We developed and tested three methods for
      creating a geocoded list of cosmetic-procedure businesses in Boston (MA) and
      Seattle (WA), USA, comparing each method on sensitivity and staff time required
      per confirmed cosmetic-procedure business. Methods varied substantially. Our
      findings represent an important step toward enabling rigorous health-linked
      spatial analyses of the health implications of this little-understood industry. 

PMID- 24322395
TI  - Radioactivity of drinking-water in the vicinity of nuclear power plants in China
      based on a large-scale monitoring study.
AB  - The public concern for radioactivity of drinking-water has been increasing in
      recent years after the rapid development of nuclear power plants, and especially
      after the Fukushima nuclear accident. In this study, the radioactivity of water
      samples collected in the vicinity of nuclear facilities from seven provinces in
      China was measured and an average annual equivalent effective dose derived from
      drinking-water ingestion was calculated. The results showed that, in winter and
      spring, the activities of gross alpha and beta ranged from 0.009 Bq/L to 0.200
      Bq/L and from 0.067 Bq/L to 0.320 Bq/L, respectively. While, in summer and
      autumn, the activities of gross a and beta varied from 0.002 Bq/L to 0.175 Bq/L
      and from 0.060 Bq/L to 0.334 Bq/L. Our results indicated that the gross a and
      beta activities in these measured water samples were below the WHO recommended
      values (0.5 Bq/L for gross alpha and 1.0 Bq/L for gross beta) and the annual
      equivalent effective dose derived from drinking-water ingestion was at a safe
      level. 

PMID- 24322396
TI  - Incorporating lag time to benefit into prevention decisions for older adults.

PMID- 24322397
TI  - Head injury as risk factor for psychiatric disorders: a nationwide register-based
      follow-up study of 113,906 persons with head injury.
AB  - OBJECTIVE: Studies investigating the relationship between head injury and
      subsequent psychiatric disorders often suffer from methodological weaknesses and
      show conflicting results. The authors investigated the incidence of severe
      psychiatric disorders following hospital contact for head injury. METHOD: The
      authors used linkable Danish nationwide population-based registers to investigate
      the incidence of schizophrenia spectrum disorders, unipolar depression, bipolar
      disorder, and organic mental disorders in 113,906 persons who had suffered head
      injuries. Data were analyzed by survival analysis and adjusted for gender, age,
      calendar year, presence of a psychiatric family history, epilepsy, infections,
      autoimmune diseases, and fractures not involving the skull or spine. RESULTS:
      Head injury was associated with a higher risk of schizophrenia (incidence rate
      ratio [IRR]=1.65, 95% CI=1.55-1.75), depression (IRR=1.59 95% CI=1.53-1.65),
      bipolar disorder (IRR=1.28, 95% CI=1.10-1.48), and organic mental disorders
      (IRR=4.39, 95% CI=3.86-4.99). This effect was larger than that of fractures not
      involving the skull or spine for schizophrenia, depression, and organic mental
      disorders, which suggests that the results were not merely due to accident
      proneness. Head injury between ages 11 and 15 years was the strongest predictor
      for subsequent development of schizophrenia, depression, and bipolar disorder.
      The added risk of mental illness following head injury did not differ between
      individuals with and without a psychiatric family history. CONCLUSIONS: This is
      the largest study to date investigating head injury and subsequent mental
      illness. The authors demonstrated an increase in risk for all psychiatric
      outcomes after head injury. The effect did not seem to be solely due to accident
      proneness, and the added risk was not more pronounced in persons with a
      psychiatric family history.

PMID- 24322400
TI  - Medicalising unhappiness: new classification of depression risks more patients
      being put on drug treatment from which they will not benefit.

PMID- 24322399
TI  - The burden of air pollution on years of life lost in Beijing, China, 2004-08:
      retrospective regression analysis of daily deaths.
AB  - OBJECTIVES: To better understand the burden of air pollution on deaths, we
      examined the effects of air pollutants on years of life lost (YLL) in Beijing,
      China. DESIGN: Retrospective regression analysis using daily time series.
      SETTING: 8 urban districts in Beijing, China. PARTICIPANTS: 80 515 deaths (48 802
      male, 31 713 female) recorded by the Beijing death classification system during
      2004-08. MAIN OUTCOME MEASURES: Associations between daily YLL and ambient air
      pollutants (particulate matter with aerodynamic diameter <2.5 um (PM2.5), PM10,
      SO2, and NO2), after adjusting for long term trends, seasonality, day of the
      week, and weather conditions. We also examined mortality risk related to air
      pollutants. RESULTS: Mean concentrations of daily PM2.5, PM10, SO2 and NO2 were
      105.1 MUg/m(3), 144.6 MUg/m(3), 48.6 MUg/m(3), and 64.2 MUg/m(3), respectively.
      All air pollutants had significant effects on years of life lost when we used
      single pollutant models. An interquartile range (IQR) increase in PM2.5, PM10,
      SO2, and NO2 was related to YLL increases of 15.8, 15.8, 16.2, and 15.1 years,
      respectively. The effects of air pollutants on YLL appeared acutely and lasted
      for two days (lag 0-1); these effects associated with an IQR increase in PM2.5
      were greater in women than men (11.1 (95% confidence interval 4.7 to 17.5) v 4.7
      (-2.9 to 12.3) YLL) and in people aged up to 65 years than those older than 65
      years (12.0 (2.9 to 21) v 3.8 (-0.9 to 8.6) YLL). The mortality risk associated
      with an IQR increase in PM2.5 was greater for people older than 65 years (2.5%
      (95% confidence interval 0.6% to 4.5%) increase of mortality) than those aged up
      to 65 years (0.7% (-0.8% to 2.2%)). CONCLUSIONS: YLL provides a complementary
      measure for examining the effect of air pollutants on mortality. Increased YLL
      are associated with increased air pollution. This study highlights the need to
      reduce air pollution in Beijing, China, to protect the health of the population.

PMID- 24322398
TI  - Role of diuretics, beta blockers, and statins in increasing the risk of diabetes
      in patients with impaired glucose tolerance: reanalysis of data from the
      NAVIGATOR study.
AB  - OBJECTIVE: To examine the degree to which use of beta blockers, statins, and
      diuretics in patients with impaired glucose tolerance and other cardiovascular
      risk factors is associated with new onset diabetes. DESIGN: Reanalysis of data
      from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes
      Research (NAVIGATOR) trial. SETTING: NAVIGATOR trial. PARTICIPANTS: Patients who
      at baseline (enrolment) were treatment naive to beta blockers (n=5640), diuretics
      (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium
      channel blocker was used as a metabolically neutral control. MAIN OUTCOME
      MEASURES: Development of new onset diabetes diagnosed by standard plasma glucose
      level in all participants and confirmed with glucose tolerance testing within 12
      weeks after the increased glucose value was recorded. The relation between each
      treatment and new onset diabetes was evaluated using marginal structural models
      for causal inference, to account for time dependent confounding in treatment
      assignment. RESULTS: During the median five years of follow-up, beta blockers
      were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353
      (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for
      baseline characteristics and time varying confounders, diuretics and statins were
      both associated with an increased risk of new onset diabetes (hazard ratio 1.23,
      95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively),
      whereas beta blockers and calcium channel blockers were not associated with new
      onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).
      CONCLUSIONS: Among people with impaired glucose tolerance and other
      cardiovascular risk factors and with serial glucose measurements, diuretics and
      statins were associated with an increased risk of new onset diabetes, whereas the
      effect of beta blockers was non-significant. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00097786.

PMID- 24322401
TI  - Patient perspective: mild depression must not be ignored.

PMID- 24322402
TI  - Michael Kidd on primary care's global challenge. Interview by Tiago Villanueva.

PMID- 24322403
TI  - A simple one-step PCR walking method and its application of bacterial rRNA for
      sequencing identification.
AB  - There are many PCR walking methods applied currently, and they all have examples
      of successful application in organisms which are more complex than bacteria.
      However, to a certain extent, it will be more convenient for researchers if the
      complicated operation and poor specificity for bacteria can be improved. Here, we
      introduced an improved one-step PCR walking method of bacteria. Using a specific
      primer of the known sequence together with a universal semirandom primer, the
      unknown sequence adjacent to a known sequence can be obtained easily by just one
      ordinary round PCR. The products can be gel purified and directly sequenced.
      Specific primers were designed according to the gene sequence of bacterial rRNA,
      and the variable and adjacent gene sequences were obtained by this method. The
      sequence analysis of the product showed that it can improve the resolution of
      bacterial identification to the species level. 

PMID- 24322404
TI  - Protein engineering of chit42 towards improvement of chitinase and antifungal
      activities.
AB  - The antagonism of Trichoderma strains usually correlates with the secretion of
      fungal cell wall degrading enzymes such as chitinases. Chitinase Chit42 is
      believed to play an important role in the biocontrol activity of Trichoderma
      strains as a biocontrol agent against phytopathogenic fungi. Chit42 lacks a
      chitin-binding domain (ChBD) which is involved in its binding activity to
      insoluble chitin. In this study, a chimeric chitinase with improved enzyme
      activity was produced by fusing a ChBD from T. atroviride chitinase 18-10 to
      Chit42. The improved chitinase containing a ChBD displayed a 1.7-fold higher
      specific activity than chit42. This increase suggests that the ChBD provides a
      strong binding capacity to insoluble chitin. Moreover, Chit42-ChBD transformants
      showed higher antifungal activity towards seven phytopathogenic fungal species. 

PMID- 24322405
TI  - Neutralizing activity induced by the attenuated coxsackievirus B3 Sabin3-like
      strain against CVB3 infection.
AB  - Coxsackievirus B3 (CVB3) causes viral myocarditis, and can ultimately result in
      dilated cardiomyopathy. There is no vaccine available for clinical use. In the
      present work, we assessed whether the Sabin3-like mutant of CVB3 could induce a
      protective immunity against virulent CVB3 Nancy and CVB4 E2 strains in mice by
      both oral and intraperitoneal (IP) routes. Serum samples, taken from mice
      inoculated with Sabin3-like, were assayed in vitro for their anti-CVB3
      neutralizing activity. CVB3 Sabin3-like was highly attenuated in vivo and was
      able to induce an anti-CVB3 activity of the serum. However, at 4 days post-CVB3
      challenge, significant increased titers of CVB3 neutralizing antibodies were
      detectable in the sera of immunized mice over the next 6 days. Non-immunized mice
      challenged with CVB3 Nancy had no anti-CVB3 activity in their sera until 10 days
      post-infection. CVB3 Nancy induced higher viral titers than did the mutant
      strain. There was no variation of the neutralizing activity of serum taken from
      mice immunized with CVB3 Sabin3-like and challenged with CVB4 E2, compared to non
      immunized mice. Despite the fact that CVB3 and CVB4 are closely related viruses,
      virus-neutralizing activity clearly distinguish between these viruses. A variable
      and limited amount of pancreatic inflammation was seen in some mice 10 days after
      Sabin3-like inoculation by IP route, whereas there was no evidence of pancreatic
      damage in mice inoculated by oral route. All immunized mice were protected from
      myocarditis and pancreatitis at 8 days post-challenge with CVB3 or CVB4 E2. These
      findings strongly suggest that the mutant strain could be considered a candidate
      for an attenuated CVB3 vaccine. 

PMID- 24322406
TI  - [Percutaneous renal mass biopsy after indeterminate diagnostic imaging results].
AB  - We conducted a retrospective study to examine the efficacy of renal mass biopsies
      in our hospital. Twenty-six patients (18 male, 8 female ; median age, 69 years ;
      range, 42-85 years) with renal masses were divided into two groups. Group 1 (n=9)
      underwent renal mass biopsies after completion of diagnostic imaging tests that
      needed a pathological diagnosis before treatment other than extirpative surgery,
      and group 2 (n=17) underwent renal mass biopsies after completion of
      indeterminate diagnostic imaging tests that did not rule out malignancy. The
      median tumor size was 2.8cm (range, 0.8-15 cm), and the median number of biopsy
      cores obtained was two (range, 2-4). There were no biopsy-associated
      complications that required intervention. In group 1, 100% (9 of 9) of the renal
      mass biopsies were diagnostic, and the pathological findings corresponded to the
      respective diagnosis obtained by imaging tests, most of which were clear cell
      carcinoma. In group 2, 59% (10 of 17) of the biopsies were diagnostic. The
      imaging characteristics of the seven nondiagnostic biopsies in group 2 were low
      blood flow and poor peripheral clarity. On the other hand, renal mass biopsies
      were indispensable for some patients in group 2 in whom the pathological findings
      led to a decision of treatment strategy. In conclusion, renal mass biopsies
      should be considered in view of their ability to compensate for limitations of
      imaging tests and their low frequency of complications.

PMID- 24322407
TI  - [A case of incidentally diagnosed retroperitoneal lymphangioleiomyomatosis with
      no respiratory symptoms].
AB  - A 39-year-old woman presented with a large retroperitoneal tumor found
      incidentally in a routine examination. The 138*37*26 mm mass was located in the
      left paraaortic region. Blood tests and urinalyses including endocrinological
      examinations revealed no abnormalities. A chest computed tomography revealed
      multiple thin-walled pulmonary cysts, which is a characteristic of
      lymphangioleiomyomatosis (LAM). Because the findings strongly suggested that the
      retroperitoneal tumor was an extrapulmonary manifestion of LAM, we performed
      laparoscopic resection of the tumor for diagnosis and treatment. The pathological
      diagnosis was LAM. The tumor cells were immunohistochemically positive for alpha 
      smooth muscle actin and weakly positive for HMB45, which is consistent with LAM.
      The cells were also positive for estrogen receptor (ER) and progesterone receptor
      (PgR). LAM is a rare progressive disease that affects mainly the lung, and leads
      to chronic respiratory failure. Extrapulmonary LAM without respiratory symptoms,
      is extremely rare. In the past, the prognosis of LAM was poor, with a median
      survival of 8-10 years, but now 85% survive more than 10 years. In the present
      case, deterioration of pulmonary lesions was not observed during the 10 months
      follow-up. Because ERand PgRfindings were positive, we will consider hormonal
      therapy as a treatment option, when the pulmonary lesions progress in the present
      case.

PMID- 24322408
TI  - [A case of bronchogenic cyst treated as retroperitoneal tumor].
AB  - A 66-year-old man presented with a retroperitoneal mass found in a routine
      medical examination. He had no complaints and no medical history. Computed
      tomography (CT) and magnetic resonance imaging (MRI) showed a cystic mass in the
      retroperitoneal space, attached to the left crus of the diaphragm, 5.5 cm in
      size. Retroperitoneal cystic tumor was diagnosed, and transperitoneal tumor
      resection was performed. Pathological findings revealed a cyst wall lined with
      ciliated epithelium and cartilage, diagnosed as a retroperitoneal bronchogenic
      cyst. The patient was in good health at 12 months after the surgery with no
      evidence of recurrence.

PMID- 24322409
TI  - [Subclinical Cushing's syndrome with primary aldosteronism with the developing
      symptom of complications : a case report].
AB  - A 42-year-old female patient had been receiving medication for hypertension. Her
      symptoms worsened in 2007. A computed tomography image revealed a 2.5 cm round
      mass in the right adrenal gland. According to a careful examination, the patient
      was diagnosed with primary aldosteronism and subclinical Cushing's syndrome.
      There were no remarkable physical features related to Cushing's syndrome. The
      patient chose a medical therapy instead of surgery. In 2012, regardless of strict
      diet therapy, however, the patient gained 10 kg weight in a year. The diagnosis
      was the same as that determined in 2007, except for exceeding value of cortisol
      over the criterion for Cushing's syndrome. A laparoscopic right adrenalectomy was
      performed to attenuate Cushing's syndrome. The histopathological examination
      revealed an adrenocortical adenoma. The patient lost 4.5 kg of weight 2 months
      after the surgery. 

PMID- 24322410
TI  - [Renal neuroendocrine tumor (carcinoid) : a case report].
AB  - A 32-year-old man was referred to our hospital for treatment of left renal cystic
      tumor, which was detected by computed tomographic (CT) scan 3 years ago. CT scan
      showed a multilocular cyst (5 cm in diameter) with a solid tumor in the left
      kidney which was enhanced with contrast. There was no evidence of extrarenal
      invasion or distant metastasis. We performed retroperitoneal laparoscopic radical
      nephrectomy. Pathological examinations revealed a cellular arrangement specific
      to carcinoid tumor and positive for CD56 (NCAM) and neuron-specific enolase. The
      cell proliferation rate was estimated to be under 2% with Ki67 staining. The
      pathological diagnosis was renal neuroendocrine tumor (carcinoid). At the 9-month
      follow up, he had no evidence of local recurrence or metastasis.

PMID- 24322411
TI  - [Solitary metastasis to the pancreas of renal cell carcinoma : a case report].
AB  - A 62-year-old man had undergone retroperitoneoscopic radical nephrectomy for left
      renal cell carcinoma at the age of 57 years. The histopathological diagnosis was
      clear cell carcinoma of the kidney (G2, pT2a, INF beta). Five years
      postoperatively, enhanced computed tomography demonstrated strongly enhanced
      tumors on the pancreatic head and body. No other metastatic lesion was detected.
      Pancreatic endocrine tumors were not ruled out. The patient underwent enucleation
      of the pancreatic head tumor and distal pancreatectomy. The histopathological
      diagnosis of the tumors was metastatic renal cell carcinoma. Patients with renal
      cell carcinoma should receive a long-term follow-up to detect possible metastatic
      lesions other than the common metastatic sites such as the lung and bones.

PMID- 24322412
TI  - [A case report of malignant fibrous histiocytoma arising from the renal capsule].
AB  - A 58-year-old woman was found to have a tumor of the left kidney by
      ultrasonography and x-ray at a medical examination. Computed tomography showed a
      mass with calcification adjacent to the left kidney. The patient was successfully
      treated with open nephrectomy. Pathological examination revealed the malignant
      fibrous histiocytoma (MFH) arising from the renal capsule, striform-pleomorphic
      type, low grade malignancy. She was free of disease at fourteen months
      postoperatively. To our knowledge, this is the 26th case of MFH arising from the
      renal capsule in Japan.

PMID- 24322413
TI  - [Granulocyte-colony stimulating factor-producing urothelial carcinoma of right
      renal pelvis : a case report].
AB  - A 78-year-old female patient with fever and general malaise was referred to our
      hospital. Laboratory examination showed the marked elevation of leukocyte and
      serum granulocyte-colony stimulating factor (GCSF) concentration without any
      infectious sign. A computed tomography scan demonstrated irregular enhanced mass
      of the right kidney with liver metastasis. The pathological findings of the
      needle biopsy was high-grade urothelial cancer with positive staining for G-CSF
      antibody. Systemic chemotherapy with gemcitabine and cisplatin was administered.
      The patient showed a partial response and the serum G-CSF level was normalized
      after 1 course of chemotherapy. After four courses of chemotherapy, the extent of
      liver metastasis increased and the G-CSF concentration became elevated. Although
      combined chemotherapy with paclitaxel and gemcitabine was administered, the
      patient died 7 months after her first visit. 

PMID- 24322414
TI  - [Postoperative vesico ureteral reflux recurrence diagnosed by positioning the
      instillation of contrast cystography : a case report].
AB  - A 5-year-old boy was diagnosed with febrile urinary tract infection (UTI) at the
      age of 2 months. Voiding cystourethrography (VCUG) showed grade IV reflux on the
      left side. Left ureterocystoneostomy was performed at 11 months because of
      recurrent febrile UTI under antibiotic prophylaxis. VCUG 1 year after surgery
      showed no reflux. The patient developed acute focal bacterial nephritis (AFBN)
      when he was 4 years and 2 months of age, and experienced 3 episodes of AFBN
      during the following 9 months. The patient had normal urinary and bowel habits.
      Although VCUG showed no recurrence of reflux, AFBN developed in spite of
      antibiotic prophylaxis. Positioning the instillation of contrast (PIC)
      cystography under general anesthesia demonstrated the left occult reflux.
      Endoscopic injection with Deflux?R was performed simultaneously. PIC cystography
      is a useful examination in patients with persistent, repeated UTI episodes
      without any signs of reflux employing conventional diagnostic modalities.

PMID- 24322415
TI  - [A case of prostate carcinosarcoma successfully treated with combined modality
      therapy].
AB  - A 58-year-old man was referred to our hospital with dysuria and elevation of
      prostate specific antigen (38.0 ng/ml). Prostate surface was smooth and elastic
      hard on digital rectal examination. Transrectal ultrasound (TRUS) indicated
      irregular boundary and low echoic area of the prostate. Prostate biopsy specimen
      included the components of adenocarcinoma (Gleason score 9) and sarcoma. The
      tumor had extended to the rectum and metastasized to bilateral obturator lymph
      nodes and right ischial bone (cT4N1M1b). We started hormone therapy for the
      adenocarcinoma component followed by total pelvic exenteration with colostomy and
      ileal conduit diversion for the sarcoma component. In addition, pelvic cavity and
      the bone metastasis were irradiated. The patient was free of recurrence at four
      and a half years after surgery. 

PMID- 24322416
TI  - [A case of testicular tumor of ovarian epithelial type].
AB  - Testicular tumors of ovarian epithelial types are rare, and their etiology is
      unknown. Moreover, a clear treatment policy has not become settled. Under the
      diagnosis of a testicular tumor, this patient underwent a high orchiectomy, and
      the pathology revealed testicular tumor of ovarian epithelial type. CA125 was
      elevated for three years post-operatively and a recurrence was discovered in the
      left inguinal region by positron emission tomography-computed tomography.
      Therefore, tumor extirpation was performed. The pathology result confirmed the
      recurrence of testicular tumor of ovarian epithelial type. After the surgery, the
      patient was given combined therapy with paclitaxel and carboplatin, which is a
      regimen of ovarian cancer, on a triweekly basis. After five courses of this
      therapy, the patient remains in remission.

PMID- 24322417
TI  - [A case of proximal type epithelioid sarcoma of the perineum].
AB  - Epithelioid sarcomas are rare soft tissue neoplasms which occur more often in
      young people. They tend to relapse, metastatize and show poor prognosis. Proximal
      type epithelioid sarcomas arise from the more proximal part of body and are more
      malignant than distal-type epithelioid sarcomas. We present a case of proximal
      type epithelioid sarcoma which occurred in the perineum. A 24-year-old male
      visited our hospital with the chief complaint of pain in the perineum. Computed
      tomography and magnetic resonance imaging showed a tumor 30*23*17 mm in diameter
      in the perineal region. The tumor was excised regionally and the pathological
      examination with immunohistochemical staining revealed that the tumor was
      proximal-type epithelioid sarcoma. The patient is free of recurrence and
      metastasis one year after local excision.

PMID- 24322418
TI  - The "battle" against paroxysmal atrial fibrillation: is there a role for left
      atrial mechanical dyssynchrony evaluated by speckle tracking?

PMID- 24322420
TI  - Adenosine triphosphate-induced atrial fibrillation: the clinical significance and
      relevance to spontaneous atrial fibrillation.
AB  - PURPOSE: Adenosine triphosphate (ATP) frequently triggers atrial fibrillation
      (AF), but the clinical significance of this phenomenon is unknown. The purpose of
      this study was to reveal the relevance between spontaneous AF and ATP-induced AF.
      METHODS: In 81 AF patients undergoing pulmonary vein isolation (PVI), we injected
      20 mg of ATP before PVI, and recorded triggering sites of the AF induced. We also
      injected 20 mg of ATP in 44 patients receiving ablation for atrioventricular
      reciprocating tachycardia (AVRT). RESULTS: ATP provoked AF in 24 (29.6 %) of the
      81 PVI patients and atrial ectopic beats in a further 48 (59.3 %). The trigger
      site of the AF was in the PV and the right atrium in 22 (91.7 %) and 2 patients,
      respectively. In 14 of those 24 patients, spontaneous AF arose from the same
      triggering site as the ATP-induced AF. In the 48 patients with ATP-provoked
      ectopic beats, spontaneous AF arose from the same site in 13. Conversely, among
      the 34 patients demonstrating spontaneous AF initiation, AF or ectopic beats were
      provoked by ATP from the same site in 14 (41.2 %) and 13 patients (38.2 %),
      respectively. ATP provoked AF in only 2 (4.5 %) of the AVRT patients. In summary,
      ATP provoked AF or atrial ectopic beats in 88.9 % of PVI patients, 36.1 % of
      whose triggering sites matched that of the spontaneous AF, while 79.4 % of
      spontaneous AF trigger sites matched ATP-provoked AF or ectopic beat sites.
      CONCLUSIONS: ATP-induced AF was strongly associated with clinical AF, and ATP is
      useful for identifying arrhythmogenic sites.

PMID- 24322419
TI  - The infrahisian conduction system and endocavitary cardiac structures: relevance
      for the invasive electrophysiologist.

PMID- 24322422
TI  - Global screening of CK2 kinase substrates by an integrated phosphoproteomics
      workflow.
AB  - Due to its constitutive activity and ubiquitous distribution, CK2 is the most
      pleiotropic kinase among the individual members of the protein kinase
      superfamily. Identification of CK2 substrates is vital to decipher its role in
      biological processes. However, only a limited number of CK2 substrates were
      identified so far. In this study, we developed an integrated phosphoproteomics
      workflow to identify the CK2 substrates in large scale. First, in vitro kinase
      reactions with immobilized proteomes were combined with quantitative
      phosphoproteomics to identify in vitro CK2 phosphorylation sites, which leaded to
      identification of 988 sites from 581 protein substrates. To reduce false
      positives, we proposed an approach by comparing these in vitro sites with the
      public databases that collect in vivo phosphorylation sites. After the removal of
      the sites that were excluded in the databases, 605 high confident CK2 sites
      corresponding to 356 proteins were retained. The CK2 substrates identified in
      this study were based on the discovery mode, in which an unbiased overview of CK2
      substrates was provided. Our result revealed that CK2 substrates were
      significantly enriched in the spliceosomal proteins, indicating CK2 might
      regulate the functions of spliceosome. 

PMID- 24322424
TI  - Beckwith-Wiedemann and Russell-Silver Syndromes: from new molecular insights to
      the comprehension of imprinting regulation.
AB  - PURPOSE OF REVIEW: The imprinted human 11p15.5 region encompasses two imprinted
      domains important for the control of fetal growth: the H19/IGF2 domain in the
      telomeric region and the KCNQ1OT1/CDKN1C domain in the centromeric region. These
      two domains are differentially methylated and each is regulated by its own
      imprinting control region (ICR): ICR1 in the telomeric region and ICR2 in the
      centromeric region. Aberrant methylation of the 11p15.5 imprinted region, through
      genetic or epigenetic mechanisms, leads to two clinical syndromes, with opposite
      growth phenotypes: Russell-Silver Syndrome (RSS; with severe fetal and postnatal
      growth retardation) and Beckwith-Wiedemann Syndrome (BWS; an overgrowth
      syndrome). RECENT FINDINGS: In this review, we discuss the recently identified
      molecular abnormalities at 11p15.5 involved in RSS and BWS, which have led to the
      identification of cis-acting elements and trans-acting regulatory factors
      involved in the regulation of imprinting in this region. We also discuss the
      multilocus imprinting disorders identified in various human syndromes, their
      clinical outcomes and their impact on commonly identified metabolism disorders.
      SUMMARY: These new findings and progress in this field will have direct
      consequence for diagnostic and predictive tools, risk assessment and genetic
      counseling for these syndromes.

PMID- 24322425
TI  - Trina Schroer: what's cooking on dynactin. Interview by Caitlin Sedwick.

PMID- 24322426
TI  - Review series: From uncertain beginnings: initiation mechanisms of clathrin
      mediated endocytosis.
AB  - Clathrin-mediated endocytosis is a central and well-studied trafficking process
      in eukaryotic cells. How this process is initiated is likely to be a critical
      point in regulating endocytic activity spatially and temporally, but the
      underlying mechanisms are poorly understood. During the early stages of
      endocytosis three components-adaptor and accessory proteins, cargo, and lipids
      come together at the plasma membrane to begin the formation of clathrin-coated
      vesicles. Although different models have been proposed, there is still no clear
      picture of how these three components cooperate to initiate endocytosis, which
      may indicate that there is some flexibility underlying this important event. 

PMID- 24322427
TI  - Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II
      antigen processing.
AB  - Antigen preservation for presentation is a hallmark of potent antigen-presenting
      cells. In this paper, we report that in human macrophages and dendritic cells, a
      subset of phagosomes gets coated with Atg8/LC3, a component of the molecular
      machinery of macroautophagy, and maintains phagocytosed antigens for prolonged
      presentation on major histocompatibility complex class II molecules. These
      Atg8/LC3-positive phagosomes are formed around the antigen with TLR2 agonists and
      require reactive oxygen species production by NOX2 for their generation. A
      deficiency in the NOX2-dependent formation of these antigen storage phagosomes
      could contribute to compromise antifungal immune control in chronic granulomatous
      disease patients. 

PMID- 24322428
TI  - FSGS3/CD2AP is a barbed-end capping protein that stabilizes actin and strengthens
      adherens junctions.
AB  - By combining in vitro reconstitution biochemistry with a cross-linking approach,
      we have identified focal segmental glomerulosclerosis 3/CD2-associated protein
      (FSGS3/CD2AP) as a novel actin barbed-end capping protein responsible for actin
      stability at the adherens junction. FSGS3/CD2AP colocalizes with E-cadherin and
      alpha-actinin-4 at the apical junction in polarized Madin-Darby canine kidney
      (MDCK) cells. Knockdown of FSGS3/CD2AP compromised actin stability and decreased
      actin accumulation at the adherens junction. Using a novel apparatus to apply
      mechanical stress to cell-cell junctions, we showed that knockdown of FSGS3/CD2AP
      compromised adhesive strength, resulting in tearing between cells and disruption
      of barrier function. Our results reveal a novel function of FSGS3/CD2AP and a
      previously unrecognized role of barbed-end capping in junctional actin dynamics.
      Our study underscores the complexity of actin regulation at cell-cell contacts
      that involves actin activators, inhibitors, and stabilizers to control adhesive
      strength, epithelial behavior, and permeability barrier integrity. 

PMID- 24322430
TI  - Comparison of torque and discomfort produced by sinusoidal and rectangular
      alternating current electrical stimulation in the quadriceps muscle at variable
      burst duty cycles.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of neuromuscular
      electrical stimulation burst duty cycle (BDC) and current type (sinusoidal
      alternating current [sAC] vs. rectangular alternating current [rAC]) on the
      electrically induced isometric torque (EIT) and discomfort. Pulsed current (PC)
      stimulation, which corresponds to one pulse rAC, was included in testing. DESIGN:
      A repeated-measures design was used. The left quadriceps of 22 healthy subjects
      (mean +/- SD age, 33 +/- 8 yrs) were stimulated alternately with sAC and rAC
      current bursts (4-kHz carrier frequency; 71 bursts per second burst frequency) to
      produce isometric contractions. A range of BDCs were tested for sAC (7%-50%) and
      rAC (2%-18%) stimulation at fixed intensities while EIT and discomfort were
      recorded. BDC presentation order was randomized. RESULTS: Overall, both current
      types elicited peak EIT at ~14% BDC (range, 7%-21%). Significantly more EIT was
      produced by rAC than by sAC stimulation (P < 0.005). Discomfort increased with
      BDC and was similar for both current types. CONCLUSIONS: The study confirmed
      previous findings that conventional sAC stimulation (50% BDC) and pulsed current
      stimulation (rAC with 2% BDC) used in sports and rehabilitation produce similar
      EIT levels. However, rAC stimulation at low BDC (7%-18%) was more effective (+35%
      torque produced with similar discomfort) than pulsed current or conventional sAC.

PMID- 24322429
TI  - Liprin-alpha/SYD-2 determines the size of dense projections in presynaptic active
      zones in C. elegans.
AB  - Synaptic vesicle (SV) release is spatially and temporally regulated by a network
      of proteins that form the presynaptic active zone (AZ). The hallmark of most AZs
      is an electron-dense projection (DP) surrounded by SVs. Despite their importance
      for our understanding of triggered SV release, high-resolution analyses of DP
      structures are limited. Using electron microscopy, we show that DPs at
      Caenorhabditis elegans neuromuscular junctions (NMJs) were highly structured,
      composed of building units forming bays in which SVs are docked to the AZ
      membrane. Furthermore, larger ribbonlike DPs that were multimers of the NMJ
      building unit are found at synapses between inter- and motoneurons. We also
      demonstrate that DP size is determined by the activity of the AZ protein SYD
      2/Liprin-alpha. Whereas loss of syd-2 function led to smaller DPs, syd-2 gain-of
      function mutants displayed larger ribbonlike DPs through increased recruitment of
      ELKS-1/ELKS. Therefore, our data suggest that a main role of SYD-2/Liprin-alpha
      in synaptogenesis is to regulate the polymerization of DPs. 

PMID- 24322431
TI  - A rare presentation of subacute progressive ascending myelopathy secondary to
      cement leakage in percutaneous vertebroplasty.
AB  - Percutaneous vertebroplasty is used to manage osteoporotic vertebral body
      compression fractures. Although it is relatively safe, complications after
      vertebroplasty ranging from minor to devastatingly major ones have been
      described. Cement leakage into the spinal canal is one such complication.
      Subacute progressive ascending myelopathy is an infrequent neurologic
      complication after spinal cord injury, typically presenting as ascending
      neurologic deficit within weeks after the initial insult. The precise cause of
      subacute progressive ascending myelopathy still remains an enigma, considering
      the rarity of this disorder. The authors present the case of a 62-yr-old woman
      with osteoporotic vertebral fracture who underwent percutaneous vertebroplasty
      and developed T6 complete paraplegia because of cement leakage. A few weeks
      later, the neurologic level ascended to higher cervical level (C3). To date, no
      case of subacute progressive ascending myelopathy secondary to cement leakage
      after percutaneous vertebroplasty has been reported. Literature is reviewed
      regarding subacute progressive ascending myelopathy, and the rehabilitation
      challenges in the management of this patient are discussed. 

PMID- 24322432
TI  - Alternatives to mouthpiece noninvasive ventilatory support to permit dental care.
AB  - Patients who are dependent on continuous noninvasive intermittent positive
      pressure ventilation for ventilatory support via angled mouthpiece interfaces
      during daytime hours often need dental interventions that are prevented by the
      presence of the mouthpiece. To permit dental interventions, however, the
      noninvasive intermittent positive pressure ventilation can most conveniently and
      safely be delivered via nasal interface using oximetry monitoring as long as both
      sedation and supplemental oxygen are avoided. Three mouthpiece continuous
      noninvasive intermittent positive pressure ventilation users are described who
      were switched to nasal noninvasive intermittent positive pressure ventilation to
      permit dental care. The most common mistake is to fail to cover the nasal
      interface exhalation portals when switching from ventilatory assistance by
      bilevel positive airway pressure devices with passive ventilator circuits to
      portable ventilators with active ventilator circuits and exhalation valves. 

PMID- 24322433
TI  - Efficacy of therapeutic ultrasound for the management of knee osteoarthritis: a
      randomized, controlled, and double-blind study.
AB  - OBJECTIVE: The aim of this study was to compare whether the effectiveness of
      continuous ultrasound (US) was superior against pulsed US and against sham US in
      knee osteoarthritis. DESIGN: A randomized controlled study was carried out on 60
      patients diagnosed with knee osteoarthritis according to American College of
      Rheumatology. The patients were randomized into the following three treatments:
      (1) continuous US (at a frequency of 1 MHz with intensity of 1 W/cm), (2) pulse
      US (same frequency and intensity on 1:4 pulse ratio), and (3) sham US. All
      treatments were applied with 5-cm head US device five times a week for 2 weeks in
      addition to home exercise program including quadriceps isometric exercise, muscle
      strength exercises, and stretching exercises of the lower extremity muscles for
      at least three times per week. Assessments were performed at baseline, at the end
      of the treatment, and at the end of the treatments and at the sixth month using
      the following measurements: Western Ontario and McMaster University
      Osteoarthritis Index-pain, stiffness, function, visual analog scale-pain at rest,
      visual analog scale-pain on movement, visual analog scale-disease severity, and
      20-m walking time. Among these parameters, the Western Ontario and McMaster
      University Osteoarthritis Index-pain was the primary outcome. RESULTS: All groups
      showed a significant improvement in all parameters in both following visits (P <
      0.05). However, there was no significant difference between the groups. Although
      the mean reduction percent in Western Ontario and McMaster University
      Osteoarthritis Index-pain was significantly higher in group I (continuous US)
      when compared to sham group (46.5% vs 28.9%, P < 0.05) at the end of the
      treatment, this result was not found in other pain parameters. CONCLUSIONS: The
      present study demonstrated that all assessment parameters significantly improved
      in all groups without a significant difference. This result suggested that
      therapeutic US provided no additional benefit in improving pain and functions in
      addition to exercise training.

PMID- 24322434
TI  - What physical attributes underlie self-reported vs. observed ability to walk 400
      m in later life? An analysis from the InCHIANTI Study.
AB  - OBJECTIVE: The aims of this study were to evaluate and contrast the physical
      attributes that are associated with self-reported vs. observed ability to walk
      400 m among older adults. DESIGN: Analysis of baseline and 3-yr data from 1026
      participants 65 yrs or older in the InCHIANTI (Invecchiare in Chianti) study was
      conducted. Observed and self-reported ability to walk 400 m at baseline and at 3
      yrs were primary outcomes. Predictors included leg speed, leg strength, leg
      strength symmetry, range of motion, balance, and kyphosis. RESULTS: Balance, leg
      speed, leg strength, kyphosis, leg strength symmetry, and knee range of motion
      were associated with self-reported ability to walk 400 m at baseline (P < 0.001,
      c = 0.85). Balance, leg speed, and knee range of motion were associated with
      observed 400-m walk (P < 0.001, c = 0.85) at baseline. Prospectively, baseline
      leg speed and leg strength were predictive of both self-reported (P < 0.001, c =
      0.79) and observed (P < 0.001, c = 0.72) ability to walk 400 m at 3 yrs.
      CONCLUSIONS: The profiles of attributes that are associated with self-reported
      vs. observed walking ability differ. The factor most consistently associated with
      current and future walking ability is leg speed. These results draw attention to
      important foci for rehabilitation.

PMID- 24322435
TI  - RE: Ultrasound-guided corticosteroid injection for the treatment of de Quervain's
      tenosynovitis.

PMID- 24322436
TI  - Re: Alternative medicines: yes; alternatives to medicine: no.

PMID- 24322437
TI  - Physical therapy modalities and rehabilitation techniques in the management of
      neuropathic pain.
AB  - Neuropathic pain is an important problem because of its complex natural history,
      unclear etiology, and poor response to standard physical therapy agents. It
      causes severe disability unrelated to its etiology. The primary goals of the
      management of neuropathic pain are to detect the underlying cause, to define the
      differential diagnosis and eliminate risk factors, and to reduce the pain. The
      physician should also know the functional and psychologic conditions of the
      patient. Therefore, a multimodal management plan in neuropathic pain is
      essential. This review aimed to reflect a diverse point of view about various
      physical therapy modalities and rehabilitation techniques. Physical therapy
      modalities and rehabilitation techniques are important options and must be
      considered when pharmacotherapy alone is not sufficient. In addition,
      psychosocial support and cognitive behavioral therapy could also be taken into
      consideration. It has been suggested that the importance of pain rehabilitation
      techniques will increase in time and these will take a larger part in the
      management of neuropathic pain. However, it is now early to comment on these
      methods because of the lack of adequate publications. 

PMID- 24322438
TI  - Re: Ultrasound-guided corticosteroid injection for the treatment of de Quervain's
      tenosynovitis.

PMID- 24322439
TI  - Re: Alternative medicines: yes; alternatives to medicine: no.

PMID- 24322440
TI  - Investigation of base pairs containing oxidized guanine using ab initio method
      and ABEEMsigmapi polarizable force field.
AB  - The integrity of the genetic information is constantly threatened by oxidizing
      agents. Oxidized guanines have all been linked to different types of cancers.
      Theoretical approaches supplement the assorted experimental techniques, and bring
      new sight and opportunities to investigate the underlying microscopic mechanics.
      Unfortunately, there is no specific force field to DNA system including oxidized
      guanines. Taking high level ab initio calculations as benchmark, we developed the
      ABEEMsigmapi fluctuating charge force field, which uses multiple fluctuating
      charges per atom. And it was applied to study the energies, structures and
      mutations of base pairs containing oxidized guanines. The geometries were
      obtained in reference to other studies or using B3LYP/6-31+G* level optimization,
      which is more rational and timesaving among 24 quantum mechanical methods
      selected and tested by this work. The energies were determined at MP2/aug-cc-pVDZ
      level with BSSE corrections. Results show that the constructed potential function
      can accurately simulate the change of H-bond and the buckled angle formed by two
      base planes induced by oxidized guanine, and it provides reliable information of
      hydrogen bonding, stacking interaction and the mutation processes. The
      performance of ABEEMsigmapi polarizable force field in predicting the bond
      lengths, bond angles, dipole moments etc. is generally better than those of the
      common force fields. And the accuracy of ABEEMsigmapi PFF is close to that of the
      MP2 method. This shows that ABEEMsigmapi model is a reliable choice for further
      research of dynamics behavior of DNA fragment including oxidized guanine. 

PMID- 24322442
TI  - Differential expression analysis of a subset of drought-responsive GmNAC genes in
      two soybean cultivars differing in drought tolerance.
AB  - The plant-specific NAC transcription factors play important roles in plant
      response to drought stress. Here, we have compared the expression levels of a
      subset of GmNAC genes in drought-tolerant DT51 and drought-sensitive MTD720 under
      both normal and drought stress conditions aimed at identifying correlation
      between GmNAC expression levels and drought tolerance degree, as well as
      potential GmNAC candidates for genetic engineering. The expression of 23 selected
      dehydration-responsive GmNACs was assessed in both stressed and unstressed root
      tissues of DT51 and MTD720 using real-time quantitative PCR. The results
      indicated that expression of GmNACs was genotype-dependent. Seven and 13 of 23
      tested GmNACs showed higher expression levels in roots of DT51 in comparison with
      MTD720 under normal and drought stress conditions, respectively, whereas none of
      them displayed lower transcript levels under any conditions. This finding
      suggests that the higher drought tolerance of DT51 might be positively correlated
      with the higher induction of the GmNAC genes during water deficit. The drought
      inducible GmNAC011 needs to be mentioned as its transcript accumulation was more
      than 76-fold higher in drought-stressed DT51 roots relative to MTD720 roots.
      Additionally, among the GmNAC genes examined, GmNAC085, 092, 095, 101 and 109
      were not only drought-inducible but also more highly up-regulated in DT51 roots
      than in that of MTD720 under both treatment conditions. These data together
      suggest that GmNAC011, 085, 092, 095, 101 and 109 might be promising candidates
      for improvement of drought tolerance in soybean by biotechnological approaches. 

PMID- 24322441
TI  - Establishment of metabolism and transport pathways in the rodent and human fetal
      liver.
AB  - The ultimate fate of drugs and chemicals in the body is largely regulated by
      hepatic uptake, metabolism, and excretion. The liver acquires the functional
      ability to metabolize and transport chemicals during the perinatal period of
      development. Research using livers from fetal and juvenile rodents and humans has
      begun to reveal the timing, key enzymes and transporters, and regulatory factors
      that are responsible for the establishment of hepatic phase I and II metabolism
      as well as transport. The majority of this research has been limited to relative
      mRNA and protein quantification. However, the recent utilization of novel
      technology, such as RNA-Sequencing, and the improved availability and refinement
      of functional activity assays, has begun to provide more definitive information
      regarding the extent of hepatic drug disposition in the developing fetus. The
      goals of this review are to provide an overview of the early regulation of the
      major phase I and II enzymes and transporters in rodent and human livers and to
      highlight potential mechanisms that control the ontogeny of chemical metabolism
      and excretion pathways. 

PMID- 24322443
TI  - A histone-like protein induces plasmid DNA to form liquid crystals in vitro and
      gene compaction in vivo.
AB  - The liquid crystalline state is a universal phenomenon involving the formation of
      an ordered structure via a self-assembly process that has attracted attention
      from numerous scientists. In this study, the dinoflagellate histone-like protein
      HCcp3 is shown to induce super-coiled pUC18 plasmid DNA to enter a liquid
      crystalline state in vitro, and the role of HCcp3 in gene condensation in vivo is
      also presented. The plasmid DNA (pDNA)-HCcp3 complex formed birefringent
      spherical particles with a semi-crystalline selected area electronic diffraction
      (SAED) pattern. Circular dichroism (CD) titrations of pDNA and HCcp3 were
      performed. Without HCcp3, pUC18 showed the characteristic B conformation. As the
      HCcp3 concentration increased, the 273 nm band sharply shifted to 282 nm. When
      the HCcp3 concentration became high, the base pair (bp)/dimer ratio fell below
      42/1, and the CD spectra of the pDNA-HCcp3 complexes became similar to that of
      dehydrated A-form DNA. Microscopy results showed that HCcp3 compacted the super
      coiled gene into a condensed state and that inclusion bodies were formed. Our
      results indicated that HCcp3 has significant roles in gene condensation both in
      vitro and in histone-less eukaryotes in vivo. The present study indicates that
      HCcp3 has great potential for applications in non-viral gene delivery systems,
      where HCcp3 may compact genetic material to form liquid crystals. 

PMID- 24322444
TI  - Carbon nanotube-induced pulmonary granulomatous disease: Twist1 and alveolar
      macrophage M1 activation.
AB  - Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to
      several environmental risk factors, among which are some that may favor carbon
      nanotube formation. Using gene array data, we initially observed that
      bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated
      mRNA of the transcription factor, Twist1, among many M1-associated genes compared
      to healthy controls. Based on this observation we hypothesized that Twist1 mRNA
      and protein expression might become elevated in alveolar macrophages from animals
      bearing granulomas induced by carbon nanotube instillation. To address this
      hypothesis, wild-type and macrophage-specific peroxisome proliferator-activated
      receptor gamma (PPARgamma) knock out mice were given oropharyngeal instillation
      of multiwall carbon nanotubes (MWCNT). BAL cells obtained 60 days later exhibited
      significantly elevated Twist1 mRNA expression in granuloma-bearing wild-type or
      PPARgamma knock out alveolar macrophages compared to sham controls. Overall,
      Twist1 expression levels in PPARgamma knock out mice were higher than those of
      wild-type. Concurrently, BAL cells obtained from sarcoidosis patients and healthy
      controls validated gene array data: qPCR and protein analysis showed
      significantly elevated Twist1 in sarcoidosis compared to healthy controls. In
      vitro studies of alveolar macrophages from healthy controls indicated that Twist1
      was inducible by classical (M1) macrophage activation stimuli (LPS, TNFalpha) but
      not by IL-4, an inducer of alternative (M2) macrophage activation. Findings
      suggest that Twist1 represents a PPARgamma-sensitive alveolar macrophage M1
      biomarker which is induced by inflammatory granulomatous disease in the MWCNT
      model and in human sarcoidosis. 

PMID- 24322446
TI  - A negative effect of a pathogen on its vector? A plant pathogen increases the
      vulnerability of its vector to attack by natural enemies.
AB  - Plant pathogens that are dependent on arthropod vectors for transmission from
      host to host may enhance their own success by promoting vector survival and/or
      performance. The effect of pathogens on vectors may be direct or indirect, with
      indirect effects mediated by increases in host quality or reductions in the
      vulnerability of vectors to natural enemies. We investigated whether the bird
      cherry-oat aphid Rhopalosiphum padi, a vector of cereal yellow dwarf virus (CYDV)
      in wheat, experiences a reduction in rates of attack by the parasitoid wasp
      Aphidius colemani when actively harboring the plant pathogen. We manipulated the
      vector status of aphids (virus carrying or virus free) and evaluated the impact
      on the rate of attack by wasps. We found that vector status did not influence the
      survival or fecundity of aphids in the absence of parasitoids. However, virus
      carrying aphids experienced higher rates of parasitism and greater overall
      population suppression by parasitoid wasps than virus-free aphids. Moreover,
      virus-carrying aphids were accepted as hosts by wasps more often than virus-free
      aphids, with a greater number of wasps stinging virus-carrying aphids following
      assessment by antennal palpations than virus-free aphids. Therefore, counter to
      the prevailing idea that persistent vector-borne pathogens enhance the
      performance of their vectors, we found that infectious aphids actively carrying a
      plant pathogen experience greater vulnerability to natural enemies. Our results
      suggest that parasitoids may contribute to the successful biological control of
      CYDV by disproportionately impacting virus-carrying vectors, and thus reducing
      the proportion of vectors in the population that are infectious. 

PMID- 24322447
TI  - A colour tunable microcavity by weak-to-strong coupling regime transition through
      a light-switchable material.
AB  - An organic based microcavity showing fully reversible colour tunability has been
      achieved for the first time. The emission output changes according to the
      modulation from pure photonic to polaritonic resonant modes through UV
      irradiation of the light-switchable matrix. 

PMID- 24322445
TI  - Characterization of a maize Wip1 promoter in transgenic plants.
AB  - The Maize Wip1 gene encodes a wound-induced Bowman-Birk inhibitor (BBI) protein
      which is a type of serine protease inhibitor, and its expression is induced by
      wounding or infection, conferring resistance against pathogens and pests. In this
      study, the maize Wip1 promoter was isolated and its function was analyzed.
      Different truncated Wip1 promoters were fused upstream of the GUS reporter gene
      and transformed into Arabidopsis, tobacco and rice plants. We found that (1)
      several truncated maize Wip1 promoters led to strong GUS activities in both
      transgenic Arabidopsis and tobacco leaves, whereas low GUS activity was detected
      in transgenic rice leaves; (2) the Wip1 promoter was not wound-induced in
      transgenic tobacco leaves, but was induced by wounding in transgenic rice leaves;
      (3) the truncated Wip1 promoter had different activity in different organs of
      transgenic tobacco plants; (4) the transgenic plant leaves containing different
      truncated Wip1 promoters had low GUS transcripts, even though high GUS protein
      level and GUS activities were observed; (5) there was one transcription start
      site of Wip1 gene in maize and two transcription start sites of GUS in Wip1::GUS
      transgenic lines; (6) the adjacent 35S promoter which is present in the
      transformation vectors enhanced the activity of the truncated Wip1 promoters in
      transgenic tobacco leaves, but did not influence the disability of truncated
      Wip1231 promoter to respond to wounding signals. We speculate that an ACAAAA
      hexamer, several CAA trimers and several elements similar to ACAATTAC octamer in
      the 5'-untranslated region might contribute to the strong GUS activity in Wip1231
      transgenic lines, meanwhile, compared to the 5'-untranslated region from Wip1231
      transgenic lines, the additional upstream open reading frames (uORFs) in the 5'
      untranslated region from Wip1737 transgenic lines might contribute to the lower
      level of GUS transcript and GUS activity. 

PMID- 24322448
TI  - Termination of paroxysmal supraventricular tachycardia with P6 acupressure.

PMID- 24322449
TI  - Intracardiac mass of the LAA during CPB for MVR.

PMID- 24322450
TI  - High-capacity antimony sulphide nanoparticle-decorated graphene composite as
      anode for sodium-ion batteries.
AB  - Sodium-ion batteries are an alternative to lithium-ion batteries for large-scale
      applications. However, low capacity and poor rate capability of existing anodes
      are the main bottlenecks to future developments. Here we report a uniform coating
      of antimony sulphide (stibnite) on graphene, fabricated by a solution-based
      synthesis technique, as the anode material for sodium-ion batteries. It gives a
      high capacity of 730 mAh g(-1) at 50 mA g(-1), an excellent rate capability up to
      6C and a good cycle performance. The promising performance is attributed to fast
      sodium ion diffusion from the small nanoparticles, and good electrical transport
      from the intimate contact between the active material and graphene, which also
      provides a template for anchoring the nanoparticles. We also demonstrate a
      battery with the stibnite-graphene composite that is free from sodium metal,
      having energy density up to 80 Wh kg(-1). The energy density could exceed that of
      some lithium-ion batteries with further optimization. 

PMID- 24322451
TI  - Comparison of national clinical practice guidelines and recommendations on
      vaccination of adult patients with autoimmune rheumatic diseases.
AB  - The aim of the study is to identify and compare national recommendations on
      vaccination of adult patients with autoimmune rheumatic diseases (ARDs) in
      Europe, North America, and Australia. We conducted a search for recommended
      immunizations in adult patients with ARDs in the Medline database and the Web
      sites of National Rheumatologic Societies, Ministries of Health, National
      Advisory Committees on Immunization, and other relevant National Scientific
      Societies. We compared national guidelines and identified points of agreement and
      differences. Guidelines on vaccination of adult patients with ARDs were
      identified in 21 countries. Points of agreement include administering influenza
      and pneumococcal vaccines in addition to inactivated age-appropriate or travel
      related vaccines, and avoiding the use of live vaccines in immunocompromised
      patients with ARDs. The most important differences concern the steroid dose that
      induces immunosuppression, the time interval between live vaccines and the
      initiation of immunosuppressive treatment, herpes zoster vaccination, and the
      preferred pneumococcal vaccine in patients with ARDs. We observed significant
      differences among national recommendations on immunizations in patients with
      ARDs, reflecting the lack of evidence-based data. 

PMID- 24322452
TI  - Are there differences in quality of life, symptomatology and functional capacity
      among different obesity classes in women with fibromyalgia? The al-Andalus
      project.
AB  - Obesity may influence fibromyalgia severity. The present study aimed to examine
      fibromyalgia (FM) symptomatology, quality of life (QoL), and functional capacity
      across obesity class categories. A total sample of 208 obese FM patients and 108
      obese control women were included in the study. The sample was further
      categorized following the international criteria for obesity classes: obesity I
      (BMI 30.0-34.99 kg/m(2)), obesity II (BMI 35.0-39.99 kg/m(2)), and obesity III
      (BMI >=40.0 kg/m(2)). QoL was assessed by means of the Short-Form-36 Health
      Survey (SF-36) and FM symptomatology with the Fibromyalgia Impact Questionnaire
      (FIQ). Standardized field-based fitness tests were used to assess
      cardiorespiratory fitness, muscular strength, flexibility, agility, and balance.
      All the dimensions of QoL, as measured by SF-36, were worse in obese FM patients
      compared to the obese control group (all p < 0.001). Obese FM patients also
      scored worse in the entire functional capacity tests studied (all p < 0.001).
      Except for the higher FIQ-depression across obesity status categories (p < 0.05),
      no differences between obesity status groups were found in QoL and FM impact.
      However, upper-body muscular strength and cardiorespiratory fitness were worse
      across obesity class categories and pairwise comparisons showed differences
      mainly between obesity I and II (p < 0.05, and p < 0.01, respectively). The
      absence of clear differences in QoL and FM symptomatology among obesity classes
      suggests that just avoiding any obese status may be a useful advice for a better
      management of the disease. Nevertheless, upper-body muscular strength and
      cardiorespiratory fitness, which are important health indicators highly related
      to the mortality risk, were worse across obesity categories.

PMID- 24322453
TI  - Cancer-associated myositis: a 35-year retrospective study of a monocentric
      cohort.
AB  - This study is aimed at retrospectively studying cancer-associated inflammatory
      myopathies (CAM) in a cohort of patients with inflammatory myopathies. CAM were
      diagnosed if the tumor was diagnosed 2 years before or after disease onset. One
      hundred and sixty-two patients were included, 27 (17 %) had CAM. A significant
      association was observed between CAM and dermatomyositis (DM), older age and
      dysphagia at disease onset. CAM have lower creatine kinase (CK) levels at onset
      and a low prevalence of autoantibodies. In conclusion, the association of male
      sex, older age, DM, dysphagia at onset, lower CK, and autoantibodies negativity
      carries a high suspicion of CAM.

PMID- 24322454
TI  - Increased risk of stroke among patients with ankylosing spondylitis: a population
      based matched-cohort study.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. Although
      two prior studies detected increased prevalence ratios of cerebrovascular disease
      among AS patients, the results of the two studies investigating AS and stroke are
      in conflict. Therefore, the present cohort study set out to estimate the risk of
      subsequent stroke in AS patients compared with matched controls using a
      population-based dataset in Taiwan. This investigation analyzed administrative
      claims data sourced from the Taiwan National Health Insurance Database. Our study
      consisted of a study cohort comprising 1,479 AS patients and a comparison cohort
      of 5,916 subjects without AS. Cox proportional hazards regressions were performed
      to estimate the risk of subsequent stroke during the follow-up period. We also
      conducted additional analyses investigating the risk of subsequent stroke by
      gender and pharmaceutical prescription. After adjusting for chronic lower
      respiratory diseases, type 2 diabetes mellitus, hypertension, hyperlipidemia,
      renal disease, coronary heart disease, atrial fibrillation, income, and
      urbanization, compared with comparison patients, the hazard ratio for subsequent
      stroke among patients with AS was 2.3 (95 % CI 1.9-2.8). We also stratified our
      results by both gender and pharmaceutical prescription, but did not find a
      statistically significant difference for the risk of subsequent stroke either
      between men and women, or between AS patients taking various pharmaceutical
      regimens and the overall AS population. This is the first study to report an
      increased hazard ratio for subsequent stroke among AS patients when compared with
      matched comparison patients without AS. 

PMID- 24322455
TI  - Prevalence and incidence of systemic lupus erythematosus in South Korea.
AB  - The aim of this study was to estimate the nationwide prevalence and incidence of
      systemic lupus erythematosus (SLE) in South Korea. National Health Insurance
      claims data covering almost all Koreans (~50 million) during 2006-2010 were
      analyzed. Individuals with SLE were identified if (1) they had experienced at
      least one hospitalization for SLE (International Classification of Diseases, 10th
      revision code M32), (2) they had taken at least one concomitant prescription of
      immunosuppressant and hydroxychloroquine, or (3) they had taken anti-dsDNA
      antibody (>=2) or complement tests (>=2) during each calendar year. Incident
      cases were defined only if they had not been SLE prevalent for the preceding 2
      years and had been SLE prevalent for 2 years consecutively thereafter. The annual
      prevalence (per 100,000) increased slightly from 20.6 [95% confidence interval
      (95% CI) 20.2-21.0] in 2006 to 26.5 (95% CI 26.0-27.0) in 2010, and the incidence
      (per 100,000) ranged between 2.5 (95% CI 2.4-2.6) in 2008 and 2.8 (95% CI 2.7
      2.9) in 2009. The number of SLE-prevalent female patients outnumbered SLE
      prevalent male patients by approximately sixfold, with a female-to-male incidence
      ratio of ~9:1. The prevalence and incidence of SLE increased significantly with
      age, regardless of sex, to a peak the age of 30-39 years. However, while both of
      them significantly decreased thereafter in females, this tendency was not
      observed in males.

PMID- 24322459
TI  - Our ongoing digital evolution.

PMID- 24322462
TI  - Illegally marketed drug ingredients are not dietary supplements.

PMID- 24322463
TI  - Differential diagnosis: distinguishing between ghostwriting and professional
      medical writing in biomedical journals.

PMID- 24322464
TI  - Illegally marketed drug ingredients are not dietary supplements--reply.

PMID- 24322465
TI  - Differential diagnosis: distinguishing between ghostwriting and professional
      medical writing in biomedical journals--reply.

PMID- 24322466
TI  - Impact of implantable cardioverter-defibrillator therapy on a secondary
      prevention population.

PMID- 24322467
TI  - The challenge of definition and moving creative arts therapy research forward.

PMID- 24322468
TI  - Impact of implantable cardioverter-defibrillator therapy on a secondary
      prevention population--reply.

PMID- 24322469
TI  - Treatment of nonmelanoma skin cancer.

PMID- 24322470
TI  - Treatment of nonmelanoma skin cancer.

PMID- 24322471
TI  - Treatment of nonmelanoma skin cancer.

PMID- 24322472
TI  - Treatment of nonmelanoma skin cancer--reply.

PMID- 24322473
TI  - Improving clinical practice guidelines.

PMID- 24322475
TI  - Nationwide registry-based analysis of cardiovascular risk factors and adverse
      outcomes in patients treated with strontium ranelate.
AB  - National registers showed that a large proportion of patients treated with
      strontium ranelate have conditions that may now contraindicate use. The risk of
      death in strontium ranelate-treated patients was significantly higher than that
      seen in users of other osteoporosis drugs even after adjusting for cardiovascular
      risk factor profile. INTRODUCTION: The European Medicines Agency (EMA) recently
      warned that strontium ranelate should be avoided in patients with ischaemic heart
      disease (IHD), peripheral vascular disease (PVD) or cerebrovascular disease
      (CVD), and in patients with uncontrolled hypertension. We investigated to what
      extent patients beginning strontium ranelate had cardiovascular conditions and
      determined the rates of MI, stroke and death. METHODS: Using the Danish National
      Prescription Database, we identified all 3,252 patients aged 50+ who began
      strontium ranelate in 2005-2007 and 35,606 users of other osteoporosis drugs as
      controls. Hospital contacts and causes of death were retrieved from national
      registers. RESULTS: Patients starting strontium were older than patients treated
      with other osteoporosis drugs and more likely to suffer from IHD, PVD or CVD
      (combined prevalence 19.2 % in female users and 29.5 % in male users). The
      adjusted risk of MI was not significantly increased (women: HR 1.05 [95 % CI 0.79
      1.41, p = 0.73]; men: 1.28 [0.74-2.20, p = 0.38]). For stroke, the adjusted HR
      was 1.23 (0.98-1.55, p = 0.07) in women and 1.64 (0.99-2.70, p = 0.05) in men.
      All-cause mortality was higher in strontium users (women: adjusted HR 1.20 [1.10
      1.30, p < 0.001]; men: adjusted HR 1.22 [1.03-1.45, p < 0.05]). CONCLUSION:
      Patients treated with strontium ranelate have an unfavourable cardiovascular risk
      profile compared with users of other osteoporosis drugs. However, only the risk
      of death differed significantly from the rates observed in users of other
      osteoporosis drugs adjusted for risk factor profile. A large proportion of
      patients currently treated with strontium ranelate have conditions that would now
      be considered contraindications according to EMA.

PMID- 24322474
TI  - An autocalibrating algorithm for non-invasive cardiac output determination based
      on the analysis of an arterial pressure waveform recorded with radial artery
      applanation tonometry: a proof of concept pilot analysis.
AB  - We aimed to describe and evaluate an autocalibrating algorithm for determination
      of cardiac output (CO) based on the analysis of an arterial pressure (AP)
      waveform recorded using radial artery applanation tonometry (AT) in a continuous
      non-invasive manner. To exemplarily describe and evaluate the CO algorithm, we
      deliberately selected 22 intensive care unit patients with impeccable AP
      waveforms from a database including AP data obtained with AT (T-Line system;
      Tensys Medical Inc.). When recording AP data for this prospectively maintained
      database, we had simultaneously noted CO measurements obtained from just
      calibrated pulse contour analysis (PiCCO system; Pulsion Medical Systems) every
      minute. We applied the autocalibrating CO algorithm to the AT-derived AP
      waveforms and noted the computed CO values every minute during a total of 15 min
      of data recording per patient (3 * 5-min intervals). These 330 AT-derived CO (AT
      CO) values were then statistically compared to the corresponding pulse contour CO
      (PC-CO) values. Mean +/- standard deviation for PC-CO and AT-CO was 7.0 +/- 2.0
      and 6.9 +/- 2.1 L/min, respectively. The coefficient of variation for PC-CO and
      AT-CO was 0.280 and 0.299, respectively. Bland-Altman analysis demonstrated a
      bias of +0.1 L/min (standard deviation 0.8 L/min; 95% limits of agreement -1.5 to
      1.7 L/min, percentage error 23%). CO can be computed based on the analysis of the
      AP waveform recorded with AT. In the selected patients included in this pilot
      analysis, a percentage error of 23% indicates clinically acceptable agreement
      between AT-CO and PC-CO.

PMID- 24322476
TI  - Ischaemic cardiac events and use of strontium ranelate in postmenopausal
      osteoporosis: a nested case-control study in the CPRD.
AB  - We explored the cardiac safety of the osteoporosis treatment strontium ranelate
      in the UK Clinical Practice Research Datalink. While known cardiovascular risk
      factors like obesity and smoking were associated with increased cardiac risk, use
      of strontium ranelate was not associated with any increase in myocardial
      infarction or cardiovascular death. INTRODUCTION: It has been suggested that
      strontium ranelate may increase risk for cardiac events in postmenopausal
      osteoporosis. We set out to explore the cardiac safety of strontium ranelate in
      the Clinical Practice Research Datalink (CPRD) and linked datasets. METHODS: We
      performed a nested case-control study. Primary outcomes were first definite
      myocardial infarction, hospitalisation with myocardial infarction, and
      cardiovascular death. Cases and matched controls were nested in a cohort of women
      treated for osteoporosis. The association with exposure to strontium ranelate was
      analysed by multivariate conditional logistic regression. RESULTS: Of the 112,445
      women with treated postmenopausal osteoporosis, 6,487 received strontium
      ranelate. Annual incidence rates for first definite myocardial infarction (1,352
      cases), myocardial infarction with hospitalisation (1,465 cases), and
      cardiovascular death (3,619 cases) were 3.24, 6.13, and 14.66 per 1,000 patient
      years, respectively. Obesity, smoking, and cardiovascular treatments were
      associated with significant increases in risk for cardiac events. Current or past
      use of strontium ranelate was not associated with increased risk for first
      definite myocardial infarction (odds ratio [OR] 1.05, 95 % confidence interval
      [CI] 0.68-1.61 and OR 1.12, 95 % CI 0.79-1.58, respectively), hospitalisation
      with myocardial infarction (OR 0.84, 95 % CI 0.54-1.30 and OR 1.17, 95 % CI 0.83
      1.66), or cardiovascular death (OR 0.96, 95 % CI 0.76-1.21 and OR 1.16, 95 % CI
      0.94-1.43) versus patients who had never used strontium ranelate. CONCLUSIONS:
      Analysis in the CPRD did not find evidence for a higher risk for cardiac events
      associated with the use of strontium ranelate in postmenopausal osteoporosis.

PMID- 24322477
TI  - Cardiovascular safety of strontium ranelate: real-life assessment in clinical
      practice.

PMID- 24322478
TI  - Changing trends in the epidemiology of hip fracture in Spain.
AB  - Temporal trends in hip fracture incidence have recently been reported in some
      developed countries. Such data in Spain has previously been incomplete; this
      study reports the stratified incidence of hip fractures in people over 65 in
      Spain during the last 14 years. INTRODUCTION: The main objective is to establish
      whether temporal trends in hip fracture incidence in Spain exist. METHODS:
      Ecological study with data from hospital discharges nationwide. The study
      includes patients aged >= 65 years during a 14-year period (1997-2010). The
      analysis compares two periods of four years: 1997-2000 (P1) and 2007-2010 (P2).
      RESULTS: There were 119,857 fractures in men and 415,421 in women. Comparing
      periods (P1 vs P2) over 10 years, the crude incidence rate/100,000
      inhabitant/year increased an average of 2.3%/year in men and 1.4% in women. After
      adjustment, the rate increased an average of 0.4%/year in men (p < 0.0001), but
      decreased 0.2%/year in women (p < 0.0001). In men, younger than 85, the decrease
      was not significant except in 70-74 years, and from 80 years, the adjusted rate
      increases significantly (p < 0.0001). In women under 80 years of age, the
      decrease in adjusted rate was significant; there was no change in 80-84 years,
      and the adjusted rate increased significantly in individuals 85 years and older
      (p < 0.0001). Mortality rates declined by 22% in both sexes, and the index of
      overaging population rises 30.1 % in men and 25.2% in women. CONCLUSIONS: This
      study supports other international studies by showing changes in the incidence of
      hip fractures after age-population adjustment, which denotes a decrease in the
      younger age groups and among women and shows an increase in both groups over 85
      years. The increase in the crude incidence rate of hip fracture in Spain reflects
      changes in population structure.

PMID- 24322480
TI  - Disability, anxiety and depression associated with medication-overuse headache
      can be considerably reduced by detoxification and prophylactic treatment. Results
      from a multicentre, multinational study (COMOESTAS project).
AB  - OBJECTIVE: The objective of this article is to investigate whether headache
      related disability, depression and anxiety can be reduced by detoxification and
      prophylactic treatment in patients with medication-overuse headache (MOH).
      METHODS: Patients with MOH were included from six centres in Europe and Latin
      America in a seven-month cohort study. Before and six months after treatment, the
      degree of disability was measured by the Migraine Disability Assessment (MIDAS)
      questionnaire, while anxiety and depression were measured by the Hospital Anxiety
      and Depression Scale (HADS). RESULTS: A total of 694 patients with MOH were
      included, of whom 492 completed the study. Headache days were reduced by 58.4%
      from 23.6 to 9.8 days per month at six months ( P < 0.001). The MIDAS score was
      reduced by 57.1% from baseline 59.9 to 25.7 ( P < 0.001). Number of patients with
      depression was reduced by 50.7% from 195 to 96 and number of those with anxiety
      was reduced by 27.1% from 284 to 207 (both P < 0.001). CONCLUSIONS: Disability,
      depression and anxiety were considerably reduced in patients with MOH by
      detoxification and prophylactic treatment. This emphasises the urgent need for
      increased awareness about avoiding overuse of headache medications and
      demonstrates that not only headache frequency but also disability are remarkably
      improved by adequate intervention.

PMID- 24322479
TI  - Nitric oxide signaling in mechanical adaptation of bone.
AB  - One of the most serious healthcare problems in the world is bone loss and
      fractures due to a lack of physical activity in elderly people as well as in
      bedridden patients or otherwise inactive youth. Crucial here are the osteocytes.
      Buried within our bones, these cells are believed to be the mechanosensors that
      stimulate bone formation in the presence of mechanical stimuli and bone
      resorption in the absence of such stimuli. Intercellular signaling is an
      important physiological phenomenon involved in maintaining homeostasis in all
      tissues. In bone, intercellular communication via chemical signals like NO plays
      a critical role in the dynamic process of bone remodeling. If bones are
      mechanically loaded, fluid flows through minute channels in the bone matrix,
      resulting in shear stress on the cell membrane that activates the osteocyte.
      Activated osteocytes produce signaling molecules like NO, which modulate the
      activity of the bone-forming osteoblasts and the bone-resorbing osteoclasts,
      thereby orchestrating bone adaptation to mechanical loading. In this review, we
      highlight current insights in the role of NO in the mechanical adaptation of bone
      mass and structure, with emphasis on its role in local bone gain and loss as well
      as in remodeling supervised by osteocytes. Since mechanical stimuli and NO
      production enhance bone strength and fracture resistance, these new insights may
      facilitate the development of novel osteoporosis treatments. 

PMID- 24322481
TI  - Phosphodiesterases 3 and 5 express activity in the trigeminal ganglion and co
      localize with calcitonin gene-related peptide.
AB  - BACKGROUND: Understanding of the neuropathology leading to migraine pain has
      centered on either a vascular or neuronal origin. Sildenafil, a specific
      inhibitor of phosphodiesterase 5 (PDE5), induces migraine-like headache in a
      human headache model without concomitant artery dilation. The presence and
      activity of PDE3 and PDE5 is known in cerebral arteries. However, the presence in
      the neuronal part of the trigeminovascular pathway, i.e. the trigeminal ganglion
      and the possible co-localization with calcitonin gene-related peptide (CGRP), is
      not known. METHODS: Rat trigeminal ganglia were isolated and immunohistochemistry
      and in situ hybridization was applied. Evaluations of cyclic adenosine
      monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) hydrolysis were
      performed using scintillation proximity assays. RESULTS: PDE3 and PDE5 were
      present and active in the trigeminal ganglia. A subset of PDE3- and PDE5-positive
      neurons contained CGRP. In contrast to cGMP, both sildenafil and cilostazol
      influenced cAMP hydrolysis. INTERPRETATION: Sildenafil may exert its effect on
      the neuronal part of the migraine pain pathway. In addition to the effects on
      cGMP signaling, sildenafil may indirectly affect cAMP signaling in the trigeminal
      ganglion. This result may suggest a common cAMP-related pathway for sildenafil,
      cilostazol, and CGRP in eliciting migraine pain.

PMID- 24322482
TI  - Treating medication overuse headache: more than improving headache.

PMID- 24322483
TI  - A randomized trial of telephone-based motivational interviewing for adolescent
      chronic headache with medication overuse.
AB  - INTRODUCTION: Nearly 2% of youths suffer from chronic migraine or chronic tension
      type headache (CTTH). A contributing factor in approximately 20%-50% of these
      youths is medication overuse, which involves taking analgesics three or more
      times per week for three months. The objective of this study was to test
      motivational interviewing (MI) as an approach to promote adherence to
      recommendations regarding not only analgesic overuse but also other aspects of
      treatment plans. METHODS: A randomized controlled trial was conducted comparing
      the experimental condition (standard of care clinic-based treatment with
      supplemental MI phone calls; N = 24) to a control condition (standard of care
      clinic-based treatment without these supplemental MI phone calls; N = 23). Four
      months after enrollment, a research assistant who was blinded to study condition
      telephoned adolescents inquiring about headache frequency, headache severity, and
      disability. RESULTS: Headache frequency was lower in the experimental condition
      versus control condition for those with relatively lower initial levels of
      headache frequency. In contrast, we did not find greater improvement in headache
      severity and disability for the experimental condition relative to the control
      condition. DISCUSSION: Our findings provided some preliminary, albeit limited,
      support for MI as an approach to improve outcomes for adolescent medication
      overuse headache (MOH).

PMID- 24322485
TI  - Cerebral microbleeds and cognition: the epidemiology of dementia in Singapore
      study.
AB  - Cerebral microbleeds (CMBs) are considered to be a novel marker of cerebral small
      vessel disease. However, the link with cognitive impairment remains unclear. We
      investigated whether CMBs-independent of other traditional markers of cerebral
      small vessel disease-are related to cognition. Chinese subjects from the
      population-based Singapore Chinese Eye Study, who failed an initial cognitive
      screening and were recruited into the ongoing Epidemiology of Dementia in
      Singapore Study, underwent neuropsychological testing and 3 T brain magnetic
      resonance imaging. The presence and number of CMBs were graded using Brain
      Observer Microbleed Scale on susceptibility-weighted images. Other magnetic
      resonance imaging lesions that were graded included presence of lacunes, white
      matter lesion, and total brain volumes. A comprehensive neuropsychological
      battery was administered and cognitive function was summarized as composite and
      domain-specific Z-scores. Among 282 subjects, 91 had any CMBs (32.3%), of whom 36
      (12.8%) had multiple CMBs. CMBs were-independent of cardiovascular risk factors
      and other markers of cerebral small vessel disease-significantly associated with
      poorer cognitive function as reflected by composite Z-score (mean difference per
      CMB increase: -0.06; 95% confidence interval: -0.11, -0.01] and with domain
      specific Z-scores including executive function, attention, and visuoconstruction.
      Among Chinese subjects CMBs were, independent of other concomitant markers of
      cerebral small vessel disease, associated with poorer cognitive function. 

PMID- 24322484
TI  - Facilitating Alzheimer disease research recruitment.
AB  - Alzheimer disease (AD) research faces challenges to successful enrollment,
      especially to clinical trials and biomarker studies. Failure to recruit the
      planned number of participants in a timely manner threatens the internal validity
      and success of clinical research, raising concerns about external validity and
      generalizability of results, and possibly leading to disparities in disease
      treatment. Methods to improve recruitment exist, but require varying levels of
      staff effort and financial resources, and evidence of effectiveness is often
      lacking or inconsistent. In this review, we summarize some of the available
      methods to improve AD research recruitment, the available literature to support
      or refute these strategies, and some of the experiences at the authors' AD
      Research Centers. We discuss the use of community-based participatory research
      principles and participant registries as a means to enhance research enrollment
      and increase diversity of research samples. 

PMID- 24322486
TI  - Advances in the diagnosis and treatment of eosinophilia.
AB  - PURPOSE OF REVIEW: Eosinophils play an important role in the pathogenesis of
      allergic, infectious and malignant diseases. Over the last decade, new diagnostic
      tools and treatment modalities have led to the re-evaluation of the existing
      definition of eosinophilic disorders. This review discusses a recent proposal for
      new terminology and classification of hypereosinophilia. The results of targeted
      therapy for hypereosinophilia-related disorders are also summarized. RECENT
      FINDINGS: A panel of multidisciplinary experts agreed on unifying definitions and
      criteria of eosinophilia-associated disorders and created a new classification of
      hypereosinophilia-related conditions based on clinical, haematological and
      laboratory findings as well as the underlying cause of hypereosinophilia. Recent
      results of the treatment of idiopathic hypereosinophilic syndrome (HES) with the
      anti-interleukin 5 monoclonal antibody mepolizumab showed its efficacy and
      manageable safety profile. The treatment of platelet-derived growth factor alpha
      (PDGFRA)-positive HES with imatinib demonstrated long-lasting efficacy and low
      likelihood of drug resistance. SUMMARY: The unifying terminology and definitions
      should aid physicians caring for patients with hypereosinophilia. Despite much
      progress, serum biomarkers correlate with disease severity and predict responses
      to treatment that are needed. There is also a great need for understanding and
      specific therapy for PDGFRA-negative HES.

PMID- 24322489
TI  - Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine
      and imidazacridine derivatives.
AB  - Thiazacridine and imidazacridine derivatives have shown promising results as
      tumors suppressors in some cancer cell lines. For a better understanding of the
      mechanism of action of these compounds, binding studies of 5-acridin-9
      ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2
      thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one
      and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by
      electronic absorption and fluorescence spectroscopy and circular dichroism
      spectroscopy were performed. The binding constants ranged from 1.46 * 10(4) to
      6.01 * 10(4) M(-1). UV-Vis, fluorescence and circular dichroism measurements
      indicated that the compounds interact effectively with ctDNA, both by
      intercalation or external binding. They demonstrated inhibitory activities to
      human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3
      thiazolidin-4-one. These results provide insight into the DNA binding mechanism
      of imidazacridines and thiazacridines.

PMID- 24322487
TI  - Neutropenia in the newborn.
AB  - PURPOSE OF REVIEW: The aim is to review normal blood neutrophil concentrations
      and the clinical approach to neutropenia in the neonatal period. A literature
      search on neonatal neutropenia was performed using the databases PubMed, EMBASE,
      and Scopus, and the electronic archive of abstracts presented at the annual
      meetings of the Pediatric Academic Societies. RECENT FINDINGS: The review
      summarizes current knowledge on the causes of neutropenia in premature and
      critically ill neonates, focusing on common causes such as maternal hypertension,
      neonatal sepsis, twin-twin transfusion, alloimmunization, and hemolytic disease.
      The article provides a rational approach to diagnosis and treatment of neonatal
      neutropenia, including current evidence on the role of recombinant hematopoietic
      growth factors. SUMMARY: Neutrophil counts should be carefully evaluated in
      premature and critically ill neonates. Although neutropenia is usually benign and
      runs a self-limited course in most neonates, it can be prolonged, and it
      constitutes a serious deficiency in antimicrobial defense in some infants.

PMID- 24322490
TI  - Synthesis and pharmacological activities of some new triazolo- and
      tetrazolopyrimidine derivatives.
AB  - A new series of fused triazolo- and tetrazolopyrimidine derivatives 2-14 were
      synthesized and their anti-inflammatory and ulcerogenic activities were
      evaluated. The pharmacological screening showed that many of these obtained
      compounds have good anti-inflammatory activities, comparable to the reference
      drug. The toxicity of the compounds was also assayed via the determination of
      their LD50 values. The structures of newly synthesized compounds were confirmed
      by IR, 1H-NMR, MS spectral data and elemental analysis. 

PMID- 24322491
TI  - Multicomponent click synthesis of new 1,2,3-triazole derivatives of pyrimidine
      nucleobases: promising acidic corrosion inhibitors for steel.
AB  - A series of new mono-1,2,3-triazole derivatives of pyrimidine nucleobases were
      synthesized by one-pot copper(I)-catalyzed 1,3-dipolar cycloaddition reactions
      between N-1-propargyluracil and thymine, sodium azide and several benzyl halides.
      The desired heterocyclic compounds were obtained in good yields and characterized
      by NMR, IR, and high resolution mass spectrometry. These compounds were
      investigated as corrosion inhibitors for steel in 1 M HCl solution, using
      electrochemical impedance spectroscopy (EIS) technique. The results indicate that
      these heterocyclic compounds are promising acidic corrosion inhibitors for steel.

PMID- 24322492
TI  - Syntheses of four enantiomers of 2,3-diendo- and 3-endo-aminobicyclo[2.2.2]oct-5
      ene-2-exo-carboxylic acid and their saturated analogues.
AB  - Ethyl 2,3-diendo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylate ((+/-)-1) was
      resolved with O,O'-dibenzoyltartaric acid via diastereomeric salt formation. The
      efficient synthesis of the enantiomers of 2,3-diendo-3-aminobicyclo[2.2.2]oct-5
      ene-2-carboxylic acid ((+)-7 and (-)-7), 3-endo-aminobicyclo[2.2.2]oct-5-ene-2
      exo-carboxylic acid ((+)-5 and (-)-5), cis- and trans-3-aminobicyclo[2.2.2]octane
      2-carboxylic acid ((+)-6, (-)-6, (+)-8 and (-)-8) was achieved via isomerization,
      hydrogenation and hydrolysis of the corresponding esters (-)-1 and (+)-1. The
      stereochemistry and relative configurations of the synthesized compounds were
      determined by NMR spectroscopy (based on the 3J(H,H) coupling constants) and X
      ray crystallography. 

PMID- 24322493
TI  - Maternal high fat feeding does not have long-lasting effects on body composition
      and bone health in female and male Wistar rat offspring at young adulthood.
AB  - High fat diets adversely affect body composition, bone mineral and strength, and
      alter bone fatty acid composition. It is unclear if maternal high fat (HF)
      feeding permanently alters offspring body composition and bone health. Female
      rats were fed control (CON) or HF diet for 10 weeks, bred, and continued their
      diets throughout pregnancy and lactation. Male and female offspring were studied
      at weaning and 3 months, following consumption of CON diet. At weaning, but not 3
      months of age, male and female offspring from dams fed HF diet had lower lean
      mass and higher fat and bone mass, and higher femur bone mineral density (females
      only) than offspring of dams fed CON diet. Male and female offspring femurs from
      dams fed HF diet had higher monounsaturates and lower n6 polyunsaturates at
      weaning than offspring from dams fed CON diet, where females from dams fed HF
      diet had higher saturates and lower n6 polyunsaturates at 3 months of age. There
      were no differences in strength of femurs or lumbar vertebrae at 3 months of age
      in either male or female offspring. In conclusion, maternal HF feeding did not
      permanently affect body composition and bone health at young adulthood in
      offspring. 

PMID- 24322494
TI  - Implications of partial conjugation of whey protein isolate to durian seed gum
      through Maillard reactions: foaming properties, water holding capacity and
      interfacial activity.
AB  - This paper deals with the conjugation of durian seed gum (DSG) with whey protein
      isolate (WPI) through Maillard reactions. Subsequently, the functional properties
      of durian seed gum in the non-conjugated (control sample) and conjugated forms
      were compared with several commercial gums (i.e., Arabic gum, sodium alginate,
      kappa carrageenan, guar gum, and pectin). The current study revealed that the
      conjugation of durian seed gum with whey protein isolate significantly (p < 0.05)
      improved its foaming properties. In this study, the conjugated durian seed gum
      produced the most stable foam among all samples. On the other hand, the emulsion
      stabilized with the conjugated durian seed gum also showed more uniform particles
      with a larger specific surface area than the emulsion containing the non
      conjugated durian seed gum. The conjugated durian seed gum showed significant
      different foaming properties, specific surface area, particle uniformity and
      water holding capacity (WHC) as compared to the target polysaccharide gums. The
      conjugated durian seed gum showed more similar functional properties to Arabic
      gum rather than other studied gums. 

PMID- 24322495
TI  - Polyketides from the halotolerant fungus Myrothecium sp. GS-17.
AB  - Two new polyketides, myrothecol (1) and 5-hydroxy-3-methyl-4-(1-hydroxylethyl)
      furan-2(5H)-one (2), were isolated from the fermentation broth of the
      halotolerant fungus Myrothecium sp. GS-17 along with three known compounds, 5
      hydroxyl-3-[(1S)-1-hydroxyethyl]-4-methylfuran-2(5H)-one (3), 3,5-dimethyl-4-
      hydroxylmethyl-5-methoxyfuran-2(5H)-one (4), and 3,5-dimethyl-4-hydroxymethyl-5-
      hydroxyfuran-2(5H)-one (5). Compound 1 is the first natural occurring polyketide
      with a unique furylisobenzofuran skeleton. The structures of these compounds were
      established via extensive spectroscopic analyses including 1D-, 2D-NMR, HRESI-MS,
      and crystal X-ray diffraction analysis.

PMID- 24322496
TI  - Toxicity and outcome of children and adolescents participating in phase I/II
      trials of novel anticancer drugs: the Royal Marsden experience.
AB  - Early phase trials are crucial in developing new therapies for poor prognosis
      childhood malignancies. Outcomes and toxicities of children treated on phase I/II
      trials at the Royal Marsden, one of the largest pediatric oncology early phase
      trial units in Europe, were examined to provide a baseline dataset and generate
      hypotheses. All patients recruited over a 10-year period to December 2011 were
      included. Variables including baseline characteristics, time on study, survival,
      toxicities, and admissions were collected. Seventy-two patients were recruited to
      21 trials (5 phase I, 16 phase II; overall 12 involved molecularly targeted
      agents). Median age at consent was 12.4 years. Dose-limiting toxicities were rare
      in phase I trial participants (2 of 15 evaluable patients, 13%); the most common
      reason for leaving trials was disease progression (76%), rather than drug
      toxicity (1.7%). Median time on trial was 1.3 months (phase I patients) and 3.3
      months (phase II). Early phase trials in children are safe and unexpected toxic
      side effects are infrequent. Patients and their families are willing to travel to
      access novel therapies, although the overall prognosis for these individuals is
      poor. Continued expansion of the portfolio is needed ultimately to improve the
      outcomes for those with resistant disease. 

PMID- 24322497
TI  - Health-related quality of life of Egyptian children with immune thrombocytopenia
      and their parents.
AB  - Health-related quality of life has been recognized as an important pediatric
      outcome measurement. Kid's ITP Tool was used to measure health-related quality of
      life of 80 Egyptian children with immune thrombocytopenia and their parents in
      relation to different disease parameters. A positive correlation between scores
      of child/proxy reports and parent report was found. Patients with newly diagnosed
      immune thrombocytopenia had significantly lower scores of both child/proxy
      reports and parent reports than chronic patients. Longer duration of illness was
      correlated with higher scores of child/proxy reports. Negative correlations were
      found between severity of bleeding and both scores of child/proxy reports and
      parent reports. Platelet count was positively correlated with parent report
      score. Regression analysis revealed that severity of bleeding had the highest
      significant impact on parent report score. Improving parents' knowledge about the
      pathogenesis and course of the disease may improve their quality of life. 

PMID- 24322498
TI  - Acute myocardial ischemia in association with acute respiratory acidosis in
      hemoglobin SC disease: a case report.

PMID- 24322499
TI  - Cytosine arabinoside and mitoxantrone followed by second allogeneic transplant
      for the treatment of children with refractory juvenile myelomonocytic leukemia.
AB  - Hematopoietic stem cell transplantation (HSCT) remains the only curative option
      for most patients with juvenile myelomonocytic leukemia (JMML). However,
      persistent disease and relapse rates after transplant range from 26% to 58%. We
      report the successful use of second HSCT after preparation with mitoxantrone and
      cytosine arabinoside (Ara-C) for patients with refractory or recurrent disease.
      Between 1993 and 2006, 5 children who underwent HSCT at our institution as
      initial therapy for JMML had persistent disease or relapsed. Pre-HSCT
      conditioning varied and donors were either HLA-matched siblings (n=2) or matched
      unrelated donors (n=3). After initial HSCT, they subsequently received high-dose
      Ara-C (3 g/m IV) every 12 hours on days -8 through -3 and mitoxantrone (10 mg/m/d
      IV) on days -8, -7, -6 followed by second HSCT from their original donors. All 5
      patients are alive at 88, 179, 199, 234, and 246 months with no evidence of JMML,
      no significant toxicity, and 100% donor chimera as determined by PCR short-tandem
      repeat analysis. Our experience supports second transplant utilizing high-dose
      Ara-C and mitoxantrone in children with JMML who do not respond or relapse after
      first transplant. 

PMID- 24322500
TI  - Comparison of long-term outcome between white and Vietnamese children treated for
      acute lymphoblastic leukemia according to the FRALLE 2000 protocol.
AB  - AIM OF THIS STUDY: To compare the relapse-free survival (RFS) in Vietnamese
      (n=141) and white (n=94) children living in Vietnam and Belgium, respectively,
      and treated in their own country for acute lymphoblastic leukemia according to
      the same FRALLE 2000 protocol. RESULTS: RFS was significantly worse in Vietnamese
      children (hazards ratio=4.48; 95% confidence interval [CI], 2.16-9.3; P<0.01).
      The 5-year RFS was 83.8% (95% CI, 76.3%-92.0%) and 47.8% (95% CI, 35.6%-64.2%)
      for white and Vietnamese children, respectively. In the latter group, relapses
      occurred in bone marrow and cerebrospinal fluid at a much earlier stage. The
      outcome was compared at first relapse only because of different treatments
      afterward, according to the country. Both series were similar for sex, age at
      diagnosis, initial white blood cell count, cytogenetic abnormalities, and
      corticosensitivity at day 8. Higher frequency of L2-acute lymphoblastic leukemia
      (P<0.001) but lower frequency of T-acute lymphoblastic leukemia (P=0.004) were
      observed in Vietnamese children. CONCLUSIONS: Several factors may contribute to
      the poor RFS in Vietnamese children, which include the time interval before the
      first intrathecal therapy and differences in the management of drug-related
      toxicity. However, additional contribution of socioeconomic factors and/or
      variations in pharmacogenetic polymorphisms in Vietnamese patients cannot
      currently be ruled out.

PMID- 24322501
TI  - Resolution of inflammatory colitis with pegfilgrastim treatment in a case of
      severe congenital neutropenia due to glucose 6 phosphatase catalytic subunit-3
      deficiency.
AB  - Glucose 6 phosphatase catalytic subunit-3 (G6PC3) deficiency is a heterogenous
      disorder characterized by severe congenital neutropenia and a variety of
      extrahematopoietic manifestations. Inflammatory bowel disease like colitis is an
      uncommon complication of G6PC3 deficiency, described only in adolescent and
      adults. Herein, we describe inflammatory colitis in a 10-year-old girl with
      severe congenital neutropenia due to G6PC3 deficiency while she was on a high
      dose filgrastim. Switching from filgrastim to (pegylated filgrastim)
      Pegfilgrastim led to rapid resolution of colitis, weight gain, and decreased
      infections. Pegfilgrastim seems to be a better remedy for treatment of G6PC3
      deficiency complicated with inflammatory bowel disease. 

PMID- 24322502
TI  - A case of NUT midline carcinoma with complete response to gemcitabine following
      cisplatin and docetaxel.
AB  - BACKGROUND: NUT midline carcinoma (NMC) is recognized as a very rare tumor that
      most often occurs around the midline and shows NUT rearrangement. This tumor
      affects children and younger adults, progresses rapidly, and shows an extremely
      poor prognosis, even with intensive chemotherapy. Very few reports have described
      effective treatment for this tumor. METHODS: A 12-year-old girl with NMC was
      treated using cisplatin (CDDP), docetaxel, gemcitabine, pemetrexed, and
      vinorelbine. RESULTS: Imaging showed partial response with CDDP and docetaxel,
      and complete response with gemcitabine. After reexacerbation of the tumor,
      although partial response was achieved with vinorelbine, the patient died 89
      weeks after onset because of reexacerbation. CONCLUSIONS: NMC is a very rare
      disease with poor prognosis. This study is the first to report response of NMC to
      gemcitabine and vinorelbine. The findings suggest that combination chemotherapies
      including CDDP, docetaxel, gemcitabine, and vinorelbine may be a choice in the
      treatment for NMC.

PMID- 24322503
TI  - Recognition and treatment of concurrent active and neurodegenerative langerhans
      cell histiocytosis: a case report.
AB  - Langerhans cell histiocytosis (LCH) is a disorder of dendritic cell proliferation
      with subsequent tissue damage often requiring chemotherapy. Neurodegenerative LCH
      presents with neuromuscular, cognitive, and behavioral alterations typically
      occurring years after diagnosis of active LCH. We present a male child with a 4
      year history of growth arrest, polyuria, polydipsia, recurrent otitis media, and
      seborrheic dermatitis. Cutaneous biopsies confirmed LCH and chemotherapy was
      initiated. During treatment for active LCH he developed neuropsychiatric decline.
      White matter changes on brain MRI were consistent with neurodegenerative LCH.
      Treatment was changed to cytarabine and intravenous immunoglobulin. After 1 year
      of therapy the patient experienced neuropsychological improvement. 

PMID- 24322504
TI  - Unusual genetic aberrations including a deletion of KLF6 tumor suppressor gene
      revealed by integrated cytogenetic approaches in a pediatric ewing sarcoma.
AB  - Ewing sarcoma is the third most common sarcoma in children and young adults. Its
      characteristic chromosomal rearrangement results in a chimerical EWSR1-ETS
      transcription factor. Secondary genetic alterations are very common. Membranous
      expression of CD99 is seen in almost all tumors. We report 2 unusual cytogenetic
      findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding
      CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor
      supressor gene KLF6. The latter has not been described previously in pediatric
      neoplasms. Molecular pathways in tumorigenesis and genetic complexity in cancer
      are discussed.

PMID- 24322505
TI  - Influence of phosphorus application and arbuscular mycorrhizal inoculation on
      growth, foliar nitrogen mobilization, and phosphorus partitioning in cowpea
      plants.
AB  - The present study was undertaken to evaluate the effects of phosphorus (P)
      application and arbuscular mycorrhizal (AM) fungi (Funneliformis mosseae) on
      growth, foliar nitrogen mobilization, and phosphorus partitioning in cowpea
      (Vigna unguiculata cv. Vita-5) plants. The experiment was conducted in a
      greenhouse in pots containing a mixture of vermiculite and sterilized quartz
      sand. Mycorrhizal and non-mycorrhizal cowpea plants were supplied with three
      levels of soluble P (0.1 (low P), 0.5 (medium P), or 1.0 mM (high P)).Cowpea
      plants supplied with low P fertilization showed significantly (p < 0.05) higher
      root colonization than those with medium and high P fertilization at both the
      vegetative and pod-filling stages. P uptake and growth parameters of cowpea
      plants were positively influenced by mycorrhizal inoculation only in the medium P
      fertilization treatment at the vegetative stage. Lack of these effects in the
      other treatments may be linked to either a very low P supply (in the low P
      treatment at the vegetative stage) or the availability of optimal levels of
      freely diffusible P in the substrate towards the pod-filling stage due to
      accumulation with time. The N concentration in leaves of all cowpea plants were
      lower at the pod-filling stage than at the vegetative stage, presumably as a
      result of N mobilization from vegetative organs to the developing pods. This was
      however not influenced by AM fungal inoculation and may be a consequence of the
      lack of an improved plant P acquisition by the fungus at the pod-filling stage.

PMID- 24322506
TI  - Continuous harvest of marine microalgae using electrolysis: effect of pulse
      waveform of polarity exchange.
AB  - Advances in harvesting of microalgae are needed for the efficient and economical
      production of microalgal biodiesel. In addition to improvements in recovery
      efficiency, developments in harvest technology should focus on reducing the
      adverse impact of subsequent processes, and should also allow water recycling. We
      investigated a continuous electrochemical approach for microalgal biodiesel
      production. Instead of conventional DC, pulsed DC was applied as a method of
      polarity exchange and its performance was analyzed in terms of recovery
      efficiency, electricity consumption, and residual Al concentration. Under
      optimized pulsed-DC conditions, 32 % less electricity was required and 7 % less
      Al was remained after continuous harvesting and there was no decrease in recovery
      efficiency compared to the continuous harvesting by conventional DC. We also
      examined the effect of this new protocol on biodiesel quality and water
      reusability. There were no differences in the microalgal oil composition before
      and after electrolytic harvesting. In addition, the harvested oil quality, based
      on four key parameters, was superior to that produced by other terrestrial crops.
      Lastly, there was no retardation of growth in recycled medium relative to that in
      fresh medium.

PMID- 24322508
TI  - Stereoselective synthesis of folded luminogens with arene-arene stacking
      interactions and aggregation-enhanced emission.
AB  - Tetraphenylethene derivatives with a folded Z-conformation and aggregation
      enhanced emission characteristics are synthesized from 2-arylbenzophenones. The
      intramolecular rotation of the folded luminogens is partially suppressed,
      resulting in improved emission efficiencies in solutions. 

PMID- 24322507
TI  - Rapid formation of multicellular spheroids in double-emulsion droplets with
      controllable microenvironment.
AB  - An attractive option for tissue engineering is to use of multicellular spheroids
      as microtissues, particularly with stem cell spheroids. Conventional approaches
      of fabricating spheroids suffer from low throughput and polydispersity in size,
      and fail to supplement cues from extracellular matrix (ECM) for enhanced
      differentiation. In this study, we report the application of microfluidics
      generated water-in-oil-in-water (w/o/w) double-emulsion (DE) droplets as pico
      liter sized bioreactor for rapid cell assembly and well-controlled
      microenvironment for spheroid culture. Cells aggregated to form size-controllable
      (30-80 MUm) spheroids in DE droplets within 150 min and could be retrieved via a
      droplet-releasing agent. Moreover, precursor hydrogel solution can be adopted as
      the inner phase to produce spheroid-encapsulated microgels after spheroid
      formation. As an example, the encapsulation of human mesenchymal stem cells
      (hMSC) spheroids in alginate and alginate-arginine-glycine-aspartic acid (-RGD)
      microgel was demonstrated, with enhanced osteogenic differentiation further
      exhibited in the latter case.

PMID- 24322509
TI  - Recombinant human erythropoietin for treating treatment-resistant depression: a
      double-blind, randomized, placebo-controlled phase 2 trial.
AB  - Pharmacological treatments for depression have insufficient efficacy in 30-40% of
      patients and fail to reverse cognitive deficits. Erythropoietin (EPO) has
      neurotrophic actions and aids neurocognitive function. The aim of this
      exploratory study was to determine whether recombinant human EPO improves mood
      and memory in treatment-resistant depression. Forty treatment-resistant depressed
      unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score >= 17
      were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a
      double-blind, placebo-controlled, parallel-group design. Patients were assessed
      at baseline and at weeks 5, 9, and 14. Primary outcome was reduction in HDRS-17
      score. Global assessment of function (GAF) was reported in addition. Secondary
      outcome was remission rate, and tertiary outcomes were changes in Rey Auditory
      Verbal Learning Test (RAVLT), Beck Depression Inventory-21 (BDI-21), and World
      Health Organization Quality of life-BREF (WHOQOL-BREF). Exploratory outcomes were
      depression and cognition composite scores. HDRS-17, GAF, and remission rates
      showed no effects of EPO over saline at week 9 (P-value >= 0.09). However, EPO
      improved BDI (P=0.02) and WHOQOL-BREF (P=0.01), and this was maintained at follow
      up week 14 (P-values <= 0.04). EPO enhanced verbal recall (P=0.02) and
      recognition (P=0.03), which was sustained at follow-up (P-values <= 0.04).
      Exploratory analysis in patients fulfilling depression severity criteria at trial
      start revealed ameliorated HDRS-17 in EPO (N=14) vs saline groups (N=17), which
      was sustained at week 14 (P-values <= 0.05). Exploratory analysis in the complete
      cohort showed that EPO reduced depression composite at weeks 9 and 14 (P
      values=0.02). The findings of this exploratory study highlight EPO as an
      interesting compound for treatment-resistant depression, which deserves further
      investigation.

PMID- 24322513
TI  - Oculomotor nerve palsy as the presenting symptom of gummatous neurosyphilis and
      human immunodeficiency virus infection: clinical response to treatment.

PMID- 24322510
TI  - Whole-body MRI with diffusion-weighted sequence for staging of patients with
      suspected ovarian cancer: a clinical feasibility study in comparison to CT and
      FDG-PET/CT.
AB  - OBJECTIVES: To evaluate whole-body MRI with diffusion-weighted sequence (WB
      DWI/MRI) for staging and assessing operability compared with CT and FDG-PET/CT in
      patients with suspected ovarian cancer. METHODS: Thirty-two patients underwent 3
      T WB-DWI/MRI, (18) F-fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG-PET/CT) and CT before diagnostic open laparoscopy (DOL). Imaging
      findings for tumour characterisation, peritoneal and retroperitoneal staging were
      correlated with histopathology after DOL and/or open surgery. For distant
      metastases, FDG-PET/CT or image-guided biopsies were the reference standards. For
      tumour characterisation and peritoneal staging, WB-DWI/MRI was compared with CT
      and FDG-PET/CT. Interobserver agreement for WB-DWI/MRI was determined. RESULTS:
      WB-DWI/MRI showed 94 % accuracy for primary tumour characterisation compared with
      88 % for CT and 94 % for FDG-PET/CT. WB-DWI/MRI showed higher accuracy of 91 %
      for peritoneal staging compared with CT (75 %) and FDG-PET/CT (71 %). WB-DWI/MRI
      and FDG-PET/CT showed higher accuracy of 87 % for detecting retroperitoneal
      lymphadenopathies compared with CT (71 %). WB-DWI/MRI showed excellent
      correlation with FDG-PET/CT (kappa = 1.00) for detecting distant metastases
      compared with CT (kappa = 0.34). Interobserver agreement was moderate to almost
      perfect (kappa = 0.58-0.91). CONCLUSIONS: WB-DWI/MRI shows high accuracy for
      characterising primary tumours, peritoneal and distant staging compared with CT
      and FDG-PET/CT and may be valuable for assessing operability in ovarian cancer
      patients. KEY POINTS: * Whole-body MRI with diffusion weighting (WB-DWI/MRI)
      helps to assess the operability of suspected ovarian cancer. * Interobserver
      agreement is good for primary tumour characterisation, peritoneal and distant
      staging. * WB-DWI/MRI improves mesenteric/serosal metastatic spread assessment
      compared with CT and FDG-PET/CT. * Retroperitoneal/cervical-thoracic nodal
      staging using qualitative DWI criteria was reasonably accurate. * WB-DWI/MRI and
      FDG-PET/CT showed the highest diagnostic impact for detecting thoracic
      metastases.

PMID- 24322514
TI  - Recovery from ophthalmoplegia and proptosis after repair of bilateral carotid
      cavernous sinus fistulas.

PMID- 24322515
TI  - Recurrence of coccidioidal meningitis after discontinuation of fluconazole.

PMID- 24322516
TI  - Proximal lower-limb weakness in Charcot-Marie-Tooth disease.

PMID- 24322517
TI  - Proximal lower-limb weakness in Charcot-Marie-Tooth disease-reply.

PMID- 24322518
TI  - Creutzfeldt-Jakob disease.

PMID- 24322519
TI  - Next-generation phenotyping and genomic incidental findings: beyond the parkin
      example.

PMID- 24322520
TI  - Creutzfeld-Jakob disease--reply.

PMID- 24322521
TI  - Next-generation phenotyping and genomic incidental findings--reply.

PMID- 24322524
TI  - Cancer preventive efficacy of marine carotenoid fucoxanthin: cell cycle arrest
      and apoptosis.
AB  - Epidemiological investigations have shown that overcoming the risk of cancer is
      related to the consumption of green vegetables and fruits. Many compounds from
      different origins, such as terrestrial plants and marine and microbial sources,
      have been reported to have therapeutic effects of which marine sources are the
      most important because the diversity of marine life is more varied than other
      sources. Fucoxanthin is one important compound with a marine origin and belongs
      to the group of carotenoids; it can be found in marine brown seaweeds,
      macroalgae, and diatoms, all of which have remarkable biological properties.
      Numerous studies have shown that fucoxanthin has considerable medicinal potential
      and promising applications in human health. In this review, we summarize the
      anticancer effects of fucoxanthin through several different mechanisms including
      anti-proliferation, induction of apoptosis, cell cycle arrest and anti
      angiogenesis, and its possible role in the treatment of cancer. 

PMID- 24322525
TI  - Dietary magnesium and genetic interactions in diabetes and related risk factors:
      a brief overview of current knowledge.
AB  - Nutritional genomics has exploded in the last decade, yielding insights-both
      nutrigenomic and nutrigenetic-into the physiology of dietary interactions and our
      genes. Among these are insights into the regulation of magnesium transport and
      homeostasis and mechanisms underlying magnesium's role in insulin and glucose
      handling. Recent observational evidence has attempted to examine some promising
      research avenues on interaction between genetics and dietary magnesium in
      relation to diabetes and diabetes risk factors. This brief review summarizes the
      recent evidence on dietary magnesium's role in diabetes and related traits in the
      presence of underlying genetic risk, and discusses future potential research
      directions. 

PMID- 24322526
TI  - Steady state fluorescence studies of wild type recombinant cinnamoyl CoA
      reductase (Ll-CCRH1) and its active site mutants.
AB  - Fluorescence quenching and time resolved fluorescence studies of wild type
      recombinant cinnamoyl CoA reductase (Ll-CCRH1), a multitryptophan protein from
      Leucaena leucocephala and 10 different active site mutants were carried out to
      investigate tryptophan environment. The enzyme showed highest affinity for
      feruloyl CoA (K(a)  = 3.72 * 10(5) M(-1)) over other CoA esters and
      cinnamaldehydes, as determined by fluorescence spectroscopy. Quenching of the
      fluorescence by acrylamide for wild type and active site mutants was collisional
      with almost 100% of the tryptophan fluorescence accessible under native condition
      and remained same after denaturation of protein with 6 M GdnHCl. In wild type Ll
      CCRH1, the extent of quenching achieved with iodide (f(a) = 1.0) was
      significantly higher than cesium ions (f(a) = 0.33) suggesting more density of
      positive charge around surface of trp conformers under native conditions.
      Denaturation of wild type protein with 6 M GdnHCl led to significant increase in
      the quenching with cesium (f(a) = 0.54), whereas quenching with iodide ion was
      decreased (f(a) = 0.78), indicating reorientation of charge density around trp
      from positive to negative and heterogeneity in trp environment. The Stern-Volmer
      plots for wild type and mutants Ll-CCRH1 under native and denatured conditions,
      with cesium ion yielded biphasic quenching profiles. The extent of quenching for
      cesium and iodide ions under native and denatured conditions observed in active
      site mutants was significantly different from wild type Ll-CCRH1 under the same
      conditions. Thus, single substitution type mutations of active site residues
      showed heterogeneity in tryptophan microenvironment and differential degree of
      conformation of protein under native or denatured conditions.

PMID- 24322527
TI  - Computed tomographic screening for lung cancer: current practice patterns at
      leading academic medical centers.

PMID- 24322528
TI  - Simple mathematical law benchmarks human confrontations.
AB  - Many high-profile societal problems involve an individual or group repeatedly
      attacking another - from child-parent disputes, sexual violence against women,
      civil unrest, violent conflicts and acts of terror, to current cyber-attacks on
      national infrastructure and ultrafast cyber-trades attacking stockholders. There
      is an urgent need to quantify the likely severity and timing of such future acts,
      shed light on likely perpetrators, and identify intervention strategies. Here we
      present a combined analysis of multiple datasets across all these domains which
      account for >100,000 events, and show that a simple mathematical law can
      benchmark them all. We derive this benchmark and interpret it, using a minimal
      mechanistic model grounded by state-of-the-art fieldwork. Our findings provide
      quantitative predictions concerning future attacks; a tool to help detect common
      perpetrators and abnormal behaviors; insight into the trajectory of a 'lone
      wolf'; identification of a critical threshold for spreading a message or idea
      among perpetrators; an intervention strategy to erode the most lethal clusters;
      and more broadly, a quantitative starting point for cross-disciplinary theorizing
      about human aggression at the individual and group level, in both real and online
      worlds. 

PMID- 24322529
TI  - Malignant peritoneal mesothelioma: prognostic factors and oncologic outcome
      analysis.
AB  - BACKGROUND: Most patients with malignant peritoneal mesothelioma (MPM) present
      with late-stage, unresectable disease that responds poorly to systemic
      chemotherapy while, at the same time, effective targeted therapies are lacking.
      We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic
      intraperitoneal chemoperfusion (HIPEC) in MPM. METHODS: We prospectively analyzed
      65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier
      survival curves and multivariate Cox-regression models identified prognostic
      factors affecting oncologic outcomes. RESULTS: Adequate CRS was achieved in 56
      patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index
      (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology
      (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8
      %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %),
      and 60-day mortality rate was 6 %. With median follow-up of 37 months, median
      overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival
      probability of 77, 57, and 39 %, respectively. Median progression-free survival
      was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68,
      and 83 %, respectively. In a multivariate Cox-regression model, age at surgery,
      SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid,
      biphasic), and postoperative sepsis were joint significant predictors of poor
      survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15,
      incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid,
      biphasic) were joint significant predictors of disease progression (Chi square =
      30.6; p = 0.00001). CONCLUSIONS: Tumor histology, disease burden, and the ability
      to achieve adequate surgical cytoreduction are essential prognostic factors in
      MPM patients undergoing CRS/HIPEC.

PMID- 24322531
TI  - Genitourinary resection at the time of cytoreductive surgery and heated
      intraperitoneal chemotherapy for peritoneal carcinomatosis is not associated with
      increased morbidity or worsened oncologic outcomes: a case-matched study.
AB  - BACKGROUND: Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy
      (HIPEC) has gained acceptance in the treatment of peritoneal carcinomatosis with
      reported morbidity and mortality rates of 27-56 and 0-11 %, respectively. The
      safety and oncologic outcome of genitourinary repair at the time of CRS and HIPEC
      remains unclear. METHODS: We identified 170 patients who underwent CRS-HIPEC at
      our institution between July 2007 and August 2011 with a minimum follow-up of 6
      months. Thirty-four (20 %) underwent concomitant urologic reconstruction at the
      time of CRS-HIPEC and were matched by disease burden (intraoperative peritoneal
      cancer index [PCI]) and extent of surgery (DeltaPCI) with a cohort of 38 (22.3 %)
      subjects without genitourinary involvement. The primary end points considered for
      this analysis included the development of major surgical (Clavien-Dindo Class III
      V) complications and overall survival. RESULTS: Median follow-up was 9.4 months.
      The most commonly performed urologic interventions included partial cystectomy
      with primary repair in 23 (65.7 %) and segmental ureteral resection and repair in
      11 (31.4 %). Patients with genitourinary reconstruction had more total organ
      involvement (6.5 vs. 4.3, p < 0.001) and more commonly underwent enteric
      anastomoses (82.4 vs. 57.9 %, p = 0.025). No significant differences were
      observed with regard to major morbidity, need for transfusion, operative time,
      intensive care unit admission, or length of stay. Among patients with appendiceal
      or colonic tumors (n = 46), overall survival was similar between genitourinary
      reconstruction and matched cohorts: 22.5 versus 15.1 months, respectively (p =
      0.66). CONCLUSIONS: Genitourinary reconstruction at the time of CRS-HIPEC occurs
      more commonly in patients with extensive disease burden undergoing radical
      debulking, yet does not adversely influence surgical morbidity or survival.

PMID- 24322530
TI  - Sentinel node biopsy using a magnetic tracer versus standard technique: the
      SentiMAG Multicentre Trial.
AB  - BACKGROUND: The SentiMAG Multicentre Trial evaluated a new magnetic technique for
      sentinel lymph node biopsy (SLNB) against the standard (radioisotope and blue dye
      or radioisotope alone). The magnetic technique does not use radiation and
      provides both a color change (brown dye) and a handheld probe for node
      localization. The primary end point of this trial was defined as the proportion
      of sentinel nodes detected with each technique (identification rate). METHODS: A
      total of 160 women with breast cancer scheduled for SLNB, who were clinically and
      radiologically node negative, were recruited from seven centers in the United
      Kingdom and The Netherlands. SLNB was undertaken after administration of both the
      magnetic and standard tracers (radioisotope with or without blue dye). RESULTS: A
      total of 170 SLNB procedures were undertaken on 161 patients, and 1 patient was
      excluded, leaving 160 patients for further analysis. The identification rate was
      95.0 % (152 of 160) with the standard technique and 94.4 % (151 of 160) with the
      magnetic technique (0.6 % difference; 95 % upper confidence limit 4.4 %; 6.9 %
      discordance). Of the 22 % (35 of 160) of patients with lymph node involvement, 16
      % (25 of 160) had at least 1 macrometastasis, and 6 % (10 of 160) had at least a
      micrometastasis. Another 2.5 % (4 of 160) had isolated tumor cells. Of 404 lymph
      nodes removed, 297 (74 %) were true sentinel nodes. The lymph node retrieval rate
      was 2.5 nodes per patient overall, 1.9 nodes per patient with the standard
      technique, and 2.0 nodes per patient with the magnetic technique. CONCLUSIONS:
      The magnetic technique is a feasible technique for SLNB, with an identification
      rate that is not inferior to the standard technique.

PMID- 24322533
TI  - Panton-Valentine leukocidin-positive Staphylococcus aureus osteomyelitis of the
      tibia in a 10-year-old child.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is
      increasing in prevalence among asymptomatic carriers and in cases of paediatric
      soft-tissue infections alike. CA-MRSA may express virulence factors such as
      Panton-Valentine leukocidin, which makes soft-tissue and hard-tissue infections
      due to such organisms challenging to treat. We report a case of osteomyelitis of
      the proximal tibia in a 10-year-old boy and discuss its management in what is to
      the authors' knowledge the first case report of Panton-Valentine leukocidin
      positive CA-MRSA osteomyelitis in a child in the UK.

PMID- 24322532
TI  - Impact of preoperative diabetes on long-term survival after curative resection of
      pancreatic adenocarcinoma: a systematic review and meta-analysis.
AB  - BACKGROUND: Diabetes mellitus (DM) is coupled to the risk and symptomatic onset
      of pancreatic ductal adenocarcinoma (PDAC). The important question whether DM
      influences the prognosis of resected PDAC has not been systematically evaluated
      in the literature. We therefore performed a systematic review and meta-analysis
      evaluating the impact of preoperative DM on survival after curative surgery.
      METHODS: The databases Medline, Embase, Web of Science, and the Cochrane Library
      were searched for studies reporting on the impact of preoperative DM on survival
      after PDAC resection. Hazard ratios and 95 % confidence intervals (CI) were
      extracted. The meta-analysis was calculated using the random-effects model.
      RESULTS: The data search identified 4,365 abstracts that were screened for
      relevant articles. Ten retrospective studies with a cumulative sample size of
      4,471 patients were included in the qualitative review. The mean prevalence of
      preoperative DM was 26.7 % (1,067 patients), and all types of pancreatic
      resections were considered. The meta-analysis included 8 studies and demonstrated
      that preoperative DM is associated with a worse overall survival after curative
      resection of PDAC (hazard ratio 1.32, 95 % CI 1.46-1.60, P = 0.004). Only 2
      studies reported separate data for new-onset and long-standing DM. CONCLUSIONS:
      To our knowledge, this is the first meta-analysis evaluating long-term survival
      after PDAC resection in normoglycemic and diabetic patients, demonstrating a
      significantly worse outcome in the latter group. The mechanism behind this
      observation and the question whether different antidiabetic medications or early
      control of DM can improve survival in PDAC should be evaluated in further
      studies.

PMID- 24322534
TI  - Predictors of conversion from conservative to operative treatment of pediatric
      forearm fractures.
AB  - Forearm fractures occur commonly in children; however, there is still uncertainty
      on what leads to conversion from conservative to operative management. Patients
      who initially underwent closed reduction and casting for diaphyseal forearm
      fractures were evaluated for predictors of conversion to operative management. We
      found that the 20 of 124 (16%) patients in whom there was conversion to operative
      management were significantly older (11.1 vs. 5.7 nonoperative), had less
      angulation in the anterior-posterior (or coronal) plane (20.2 vs. 12.8 degrees 
      for the radius, 17.5 vs. 7.8 degrees  for the ulna), had a more proximal ulnar
      fracture location, and had more translated or shortened radius fractures.

PMID- 24322535
TI  - Staged weaning versus immediate cessation of Pavlik harness treatment for
      developmental dysplasia of the hip.
AB  - Outcomes of nonoperative treatment for developmental dysplasia of the hip were
      compared between two centres. Eighty children in Centre A underwent staged
      weaning of the Pavlik harness once three consecutive weekly ultrasounds showed
      Graf Grade I hips, whereas in 48 children in Centre B, the harness was removed
      immediately. No statistically significant difference was found in the rate of
      reintervention (repeat harness treatment, closed or open reduction), avascular
      necrosis or acetabular index between the two methods, although there was a
      nonsignificant trend towards higher reintervention rate and lower avascular
      necrosis rate with immediate harness removal. Age at start of treatment
      significantly impacted upon initial harness success, reinterventions and
      avascular necrosis. 

PMID- 24322536
TI  - The biomechanics of guided growth: does screw size, plate size, or screw
      configuration matter?
AB  - Guided growth with the eight-plate is a commonly used technique to correct
      angular limb deformities in children. However, the optimal combination of plate
      size, screw size, and screw configuration has not been determined. Using
      osteotomized femoral sawbones and a rail frame, we developed a growth model to
      examine the effect of these variables at 6-month, 12-month, and 18-month growth
      increments. The mean annual coronal plane change was 11.3 degrees . Screw size
      and plate size were not associated with the rate of angular correction. Screw
      configuration was important, with parallel screws resulting in optimal correction
      at all time points compared with divergent screws (P<0.05). 

PMID- 24322537
TI  - HIV epidemics among transgender women.
AB  - PURPOSE OF REVIEW: Recent data on the high burden of HIV among transgender women
      have stimulated interest in addressing HIV in this vulnerable population. This
      review situates the epidemiologic data on HIV among transgender women in the
      context of the social determinants of health and describes opportunities for
      effective interventions. RECENT FINDINGS: Transgender women experience unique
      vulnerability to HIV that can be attributed to multilevel, intersecting factors
      that also influence the HIV treatment and care continuum. Stigma and
      discrimination, lack of social and legal recognition of their affirmed gender,
      and exclusion from employment and educational opportunities represent fundamental
      drivers of HIV risk in transgender women worldwide. SUMMARY: Interventions to
      improve engagement in HIV prevention, testing, care, and treatment among
      transgender women should build on community strengths and address structural
      factors as well as psychosocial and biologic factors that increase HIV
      vulnerability and prevent access to HIV services.

PMID- 24322538
TI  - Orbital contributions to CO oxidation in Mo-Cu carbon monoxide dehydrogenase.
AB  - A molecular orbital analysis provides new insight into the mechanism of Mo/Cu
      carbon monoxide dehydrogenase, and reveals electronic structure contributions to
      reactivity that are remarkably similar to the structurally related molybdenum
      hydroxylases. A calculated reaction barrier of ~12 kcal mol(-1) is in excellent
      agreement with experiment.

PMID- 24322539
TI  - Operative versus nonoperative treatment of displaced midshaft clavicle fractures
      in adults: a systematic review.
AB  - OBJECTIVES: Intervention studies of clavicle fracture treatment are numerous, but
      only a few high quality studies prospectively compare operative and nonoperative
      treatment. The objective of this study was to review evidence from randomized
      controlled trials on operative versus nonoperative treatment of displaced
      midshaft clavicle fractures in adults with focus on fracture healing,
      complications and functional outcome. DATA SOURCES: An electronic search was
      performed of PubMed, Embase and Cochrane databases which revealed 559 articles.
      All articles published before October 18th 2012 and written in English, Danish or
      Swedish were eligible. STUDY SELECTION: Articles were excluded if they included
      children under the age of 16, did not include acute midshaft fractures, included
      concomitant fractures, did not meet the requirements of Level I evidence
      according to Centre for evidence based medicine 2009 guidelines, were systematic
      reviews or meta-analyses, or did not compare operative and nonoperative
      treatment. DATA EXTRACTION: Articles were parsed for relevance by two reviewers
      independently regarding title, abstract, and full text. Extraction of data was
      done by both reviewers in collaboration and sorted according to the aims of the
      study. Complications were grouped according to additional surgery required. The
      quality of studies was assessed by both reviewers in unison using Critical
      Appraisal Skills Programme 2010 checklists. CONCLUSIONS: It seems like operative
      intervention leads to fewer nonunions at the cost of an increase in minor
      complications compared to nonoperative treatment. However, the effects of
      operation on functional outcome remains controversial. High quality evidence is
      currently sparse supporting either operative or nonoperative treatment on
      displaced midshaft clavicle fractures in adults.

PMID- 24322540
TI  - Posterior stabilization of cervical spine injuries using the Roy-Camille plates:
      a long-term follow-up.
AB  - AIM: Posterior cervical spine fixation has undergone tremendous advancement in
      recent years. The purpose of this study is to present our experience with the Roy
      Camille instrumentation for posterior cervical stabilization after injury in a
      long-term follow-up. PATIENTS AND METHODS: From 1985 to 1995, 76 patients with a
      lower cervical spine traumatic lesion were treated in a single institution by
      posterior plate stabilization using the Roy-Camille plates (R-C plates). Fifty
      four men and 22 women with a mean age of 43.2 years were involved. In 59 patients
      the injuries were due to a road traffic accident, in 14 cases the fall from a
      high was responsible, while in two cases the injuries were due to sport
      activities. There were four bilateral dislocations, nine unilateral dislocations,
      56 fracture dislocations, five fracture separations of a lateral mass and two
      burst fractures. Neurological lesions were present in 65 patients (9 ASIA A, 16
      ASIA B, 22 ASIA C, 18 ASIA D and 11 ASIA E). All patients had minimum follow-up
      of 7 years. Fifty-nine patients were followed up for a mean period of 21 years
      (14-27 years). RESULTS: Stability was obtained in all but two cases. Reoperation
      was done in two cases: in one for the correction of the lost reduction and in a
      second for the reinsertion of a screw irritating a nerve root. No case in the
      ASIA A group showed neurological improvement, a fact observed in the other
      groups. CONCLUSIONS: The R-C plates were used in the last quarter of the last
      century. This technique showed good short-time results, and we have shown good
      results in a long-term follow-up as well. The literature referred to this
      technique was favorable, as far as the biomechanical behavior and also clinical
      application concern. The question about this plating system abundance still
      remains unanswered.

PMID- 24322541
TI  - Antibacterial effects of the tellurium compound OTD on E. coli isolates.
AB  - The antibacterial effects of a new organo-tellurium compound [Octa-O-bis-(R,R)
      tartarate ditellurane (OTD)] on Escherichia coli isolates as a model are shown.
      OTD was found to be a bactericidal drug. It exhibits inhibition zones on a
      protein-rich agar medium but not in a protein-poor medium unless a thiol is
      added. When applied at the lag phase, OTD inhibits more efficiently than at the
      log phase. Thiols enhance the efficiency at the log phase. OTD inhibits biofilm
      formation of E. coli. X-ray microanalysis demonstrated damage caused to the
      Na+/K+ pumps and leakage of potassium and phosphorous. Scanning electron
      microscopy demonstrated an incomplete surface of the bacterial cell wall with a
      concavity in the center that looks like a hole. Transmission electron microscopy
      demonstrated severe damage, such as depletion, perforation, and holes in the
      inner membrane. These results indicate for the first time that the new tellurium
      compound has antibacterial activities.

PMID- 24322542
TI  - A phase I study of irinotecan in combination with metronomic temozolomide in
      patients with recurrent glioblastoma.
AB  - To determine the maximum tolerated dose of irinotecan administered every 2 weeks,
      in combination with a fixed and continuous administration of temozolomide, in
      patients with glioblastoma at first relapse. Patients received oral temozolomide
      at a fixed and continuous dose of 50 mg/m divided into three daily doses, except
      for a single 100 mg/m dose, administered before every irinotecan infusion.
      Irinotecan was given intravenously on days 8 and 22 of 28-day cycles. The
      starting dose of irinotecan was 100 mg/m, and this was escalated by increments of
      15 mg/m in cohorts of 3-6 evaluable patients. Determination of the dose-limiting
      toxicity was based on toxicities recorded from day 1 of the first cycleto day 8
      of the third cycle. Enzyme-inducing antiepileptic drugs were not allowed. Tumor
      response was assessed by MRI every 8 weeks. Twelve patients were enrolled in this
      phase I study. The three patients enrolled at dose level 1 and six of nine
      patients enrolled at dose level 2 were evaluable for toxicity. The maximum
      tolerated dose of irinotecan was 100 mg/m. The dose-limiting toxicities were
      hematologic and gastrointestinal. Nine patients were evaluable for response: one
      patient achieved a partial response, four patients remained stable, and four
      patients had disease progression. The combination of metronomic temozolomide and
      irinotecan every 2 weeks can be safely administered at the recommended doses; a
      phase II study with this combination was started and has completed accrual. 

PMID- 24322543
TI  - 3-Acetyl-bis(2-chloro-4-nitrophenyl)triazene is a potent antitumor agent that
      induces oxidative stress and independently activates the stress-activated protein
      kinase/c-Jun NH2-terminal kinase pathway.
AB  - Previously, we described the synthesis and biological activity of a new class of
      anticancer molecules that preferentially target malignant cells and may serve as
      potential antitumor agents. Among several synthesized agents, we selected 3
      acetyl-1,3-bis(2-chloro-4-nitrophenyl)-1-triazene (8b) as a representative of the
      group of 4-nitro-substituted 1,3-diaryltriazenes. The aim of this study was to
      further investigate the mechanism of cell response to the 8b compound. The HeLa
      human cervical carcinoma cell line was used as an experimental model to further
      investigate the mechanism of cell response to the 8b compound. The 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay
      was used to address cell survival, and western blot (immunoblotting) was used for
      the expression of relevant proteins after 8b drug exposure. The pretreatment of
      HeLa cells with salubrinal, a specific inhibitor of endoplasmic reticulum (ER)
      stress, confirmed the importance of ER stress in apoptosis induced by 8b. We also
      demonstrate that 8b triggers the activation of stress-activated protein kinase/c
      Jun NH2-terminal kinase (SAPK/JNK) in a time-dependent and dose-dependent manner.
      Moreover, the inhibition of SAPK/JNK activity by JNK II before 8b treatment
      increased the survival rate of HeLa cells relative to survival in the presence of
      8b alone, indicating the importance of this kinase in cell death. The
      simultaneous inhibition of ER stress induction and SAPK/JNK activation increased
      the survival of HeLa cells upon 8b treatment more than inhibition of both
      pathways independently, suggesting the separate triggering of both signaling
      pathways. Our data indicate that cytotoxic activity of the novel compound 8b is
      based on its ability to induce ER stress and SAPK/JNK signaling pathways
      independently, driving cells to cell death. 

PMID- 24322544
TI  - Chemical degradation and morphological instabilities during focused ion beam
      prototyping of polymers.
AB  - Focused ion beam processing of low melting materials, such as polymers or
      biological samples, often leads to chemical and morphological instabilities which
      prevent the straight-forward application of this versatile direct-write
      structuring method. In this study the behaviour of different polymer classes
      under ion beam exposure is investigated using different patterning parameters and
      strategies with the aim of (i) correlating local temperatures with the polymers'
      chemistry and its morphological consequences; and (ii) finding a way of
      processing sensitive polymers with lowest chemical degradation while maintaining
      structuring times. It is found that during processing of polymers three
      temperature regimes can be observed: (1) at low temperatures all polymers
      investigated show stable chemical and morphological behaviour; (2) very high
      temperatures lead to strong chemical degradation which entails unpredictable
      morphologies; and (3) in the intermediate temperature regime the behaviour is
      found to be strongly material dependent. A detailed look reveals that polymers
      which rather cross-link in the proximity of the beam show stable morphologies in
      this intermediate regime, while polymers that rather undergo chain scission show
      tendencies to develop a creeping phase, where material follows the ion beam
      movement leading to instable and unpredictable morphologies. Finally a simple,
      alternative patterning strategy is suggested, which allows stable processing
      conditions with lowest chemical damage even for challenging polymers undergoing
      chain scission. 

PMID- 24322545
TI  - Improved regeneration and transformation protocols for three strawberry
      cultivars.
AB  - Strawberry (Fragaria * ananassa) is an economically important soft fruit crop
      with polyploid genome which makes the breeding of new cultivars difficult. Simple
      and efficient method for transformation and regeneration is required for
      cultivars improvement in strawberry. In the present study, adventitious shoot
      regeneration has been investigated in three cultivated strawberry plants, i.e.,
      Festival, Sweet Charly and Florida via direct organogenesis using the in vitro
      juvenile leaves as explants. Explants were collected after sub-culturing on a
      propagation medium composed of MS supplemented with 0.5 mg/l BA; 0.1 mg/l GA3 and
      0.1 mg/l IBA. To select the suitable organogenesis, the explants of the three
      cultivars were cultured on MS medium supplemented with different concentrations
      of TDZ (1, 2, 3, and 4 mg/l), then incubated at a temperature of 22  degrees C +/
      2. Medium containing 2 mg/l TDZ revealed the best regeneration efficiency with
      the three cultivars (72% for Festival, and 73% for Sweet Charly and Florida).
      After 4 weeks, the produced shoots were cultured on MS medium with different
      concentrations of BA and Kin to enhance shoot elongation. Results showed that the
      medium containing 1.5 mg/l BA and 0.5 mg/l Kin revealed highest elongation
      efficiency (88% and 94%) for Festival and Sweet Charly, respectively. On the
      other hand, medium containing 1.5 mg/l BA and 0.1 mg/l Kin showed highest
      elongation efficiency (90%) in Florida. Elongated shoots were successfully rooted
      on MS medium containing 1.5 mg/l NAA. Furthermore, transformation of the two
      cultivars, Festival and Sweet Charly, has been established via Agrobacterium
      strain LBA44404 containing the plasmid pISV2678 with gus-intron and bar genes.
      Three days post co-cultivation, GUS activity was screening using the
      histochemical assay. The results showed 16% and 18% of the tested plant materials
      has changed into blue color for Festival and Sweet Charly, respectively. Out of
      120 explants only 13 shoots were developed on bialaphos medium for each cultivar,
      representing 10.8% bialaphos resistant strawberry shoot. The presence of the both
      genes bar and uid A was detected by PCR and Northern giving a transformation
      efficiency of 5%. 

PMID- 24322546
TI  - Usefulness of fitness testing to establish metabolic syndrome in perimenopausal
      Moroccan women.
AB  - BACKGROUND: The use of fitness testing for the identification of women at high
      risk of metabolic syndrome (MS), and therefore of cardiovascular disease, is
      clinically relevant. OBJECTIVE: The purpose of this study was to determine the
      ability of a set of physical fitness tests to establish the risk of MS in
      perimenopausal Moroccan women. METHODS: The study comprised 151 women (45-65
      years) from the North of Morocco. We used standardized field-based fitness tests
      to assess cardiorespiratory fitness, muscular strength, flexibility and balance.
      Fatness was assessed by impedanciometry and anthropometry. We also measured
      resting heart rate, blood pressure and plasma fasting glucose, total cholesterol,
      low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)
      cholesterol and triglycerides. RESULTS: Women with MS performed worse in most of
      the fitness tests studied. Among the fitness test studied, the six-minute walk
      test was the most associated to MS. Receiver operating characteristics curve
      analyses revealed that the six-minute walk test threshold that best discriminated
      between the presence and absence of MS was 480.5 m (area under curve (AUC):
      0.719, 95% confidence interval (CI): 0.62-0.82; p<0.001). Logistic regression
      after adjustment for age and weight showed that a distance <=480 m is associated
      with 2.9 times higher risk (95% CI: 1.56-7.65; p<0.05) for having MS.
      CONCLUSIONS: Including cardiorespiratory fitness as a MS risk factor may improve
      early identification of at-risk Moroccan women. Fitness testing provides useful
      information and is cheap, easy to perform, and not time-consuming, which makes
      its use in this specific clinical settings feasible.

PMID- 24322547
TI  - Device therapy: ICDs in patients with a DNR order.

PMID- 24322551
TI  - Coronary artery disease: Calcium density reduces CVD risk.

PMID- 24322552
TI  - Valvular disease: Improving outcomes for aortic valve replacement in the USA.

PMID- 24322553
TI  - Anticoagulation therapy: Edoxaban noninferior to warfarin in patients with AF.

PMID- 24322550
TI  - Genetics of sudden cardiac death caused by ventricular arrhythmias.
AB  - Sudden cardiac death (SCD) resulting from ventricular tachyarrhythmia is a major
      contributor to mortality. Clinical management of SCD, currently based on clinical
      markers of SCD risk, can be improved by integrating genetic information. The
      identification of multiple disease-causing gene variants has already improved
      patient management and increased our understanding of the rare Mendelian diseases
      associated with SCD risk in the young, but marked variability in disease severity
      suggests that additional genetic modifiers exist. Next-generation DNA sequencing
      could be crucial to the discovery of SCD-associated genes, but large data sets
      can be difficult to interpret. SCD usually occurs in patients with an average age
      of 65 years who have complex cardiac disease stemming from multiple, common,
      acquired disorders. Heritable factors are largely unknown, but are likely to have
      a role in determining the risk of SCD in these patients. Numerous genetic loci
      have been identified that affect electrocardiogram indices, which are regarded as
      intermediate phenotypes for tachyarrhythmia. These loci could help to identify
      new molecules and pathways affecting cardiac electrical function. These loci are
      often located in intergenic regions, so our evolving understanding of the
      noncoding regulatory regions of the genome are likely to aid in the
      identification of novel genes that are important for cardiac electrical function
      and possibly SCD. 

PMID- 24322554
TI  - Dyslipidaemia: 1-Year results from OSLER trial of anti-PCSK9 monoclonal antibody
      evolocumab.

PMID- 24322556
TI  - Acute coronary syndromes: Using chest pain to diagnose acute MI.

PMID- 24322558
TI  - Chemical communication during foraging in the harvesting ants Messor pergandei
      and Messor andrei.
AB  - We combined behavioral analyses in the laboratory and field to investigate
      chemical communication in the formation of foraging columns in two Nearctic seed
      harvesting ants, Messor pergandei and Messor andrei. We demonstrate that both
      species use poison gland secretions to lay recruitment trails. In M. pergandei,
      the recruitment effect of the poison gland is enhanced by adding pygidial gland
      secretions. The poison glands of both species contain 1-phenyl ethanol. Minute
      quantities (3 MUl of a 0.1 ppm solution) of 1-phenyl ethanol drawn out along a 40
      cm long trail released trail following behavior in M. pergandei, while M. andrei
      required higher concentrations (0.5-1 ppm). Messor pergandei workers showed weak
      trail following to 5 ppm trails of the pyrazines 2,5-dimethylpyrazine and 2,3,5
      trimethylpyrazine, whereas M. andrei workers showed no behavioral response.
      Minute quantities of pyrazines were detected in M. pergandei but not in M. andrei
      poison glands using single ion monitoring gas chromatography-mass spectrometry. 

PMID- 24322557
TI  - An integrated systems genetics screen reveals the transcriptional structure of
      inherited predisposition to metastatic disease.
AB  - Metastasis is the result of stochastic genomic and epigenetic events leading to
      gene expression profiles that drive tumor dissemination. Here we exploit the
      principle that metastatic propensity is modified by the genetic background to
      generate prognostic gene expression signatures that illuminate regulators of
      metastasis. We also identify multiple microRNAs whose germline variation is
      causally linked to tumor progression and metastasis. We employ network analysis
      of global gene expression profiles in tumors derived from a panel of recombinant
      inbred mice to identify a network of co-expressed genes centered on Cnot2 that
      predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell
      metastatic potential in vivo, supporting a functional role for Cnot2 in
      metastasis. Small RNA sequencing of the same tumor set revealed a negative
      correlation between expression of the Mir216/217 cluster and tumor progression.
      Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the
      Mir216/217 locus, indicating that differences in expression may be inherited.
      Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo.
      Finally, small RNA sequencing and mRNA expression profiling data were integrated
      to reveal that miR-3470a/b target a high proportion of network transcripts. In
      vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover,
      Mir3470b is a likely regulator of the Cnot2 network as its overexpression down
      regulated expression of network hub genes and enhanced metastasis in vivo,
      phenocopying Cnot2 knockdown. The resulting data from this strategy identify
      Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems
      level approach in identifying modifiers of metastasis. 

PMID- 24322559
TI  - Non-adherence to prescribed home rehabilitation exercises for musculoskeletal
      injuries: the role of the patient-practitioner relationship.
AB  - OBJECTIVE: To identify which factors best explain non-adherence to home
      rehabilitation exercises (HRE) for patients with musculoskeletal injuries.
      DESIGN: Cross-sectional study. METHODS: Participants (n = 87) aged 17-91 years
      completed questionnaires measuring demographic and injury-related information,
      self-efficacy, personality, health locus of control, patient-practitioner
      relationship, optimism, health value and adherence to HRE. In addition, each
      participant's attending physiotherapist assessed the participant's adherence and
      effort during the appointment. RESULTS: A hierarchical regression with 3 steps
      (step 1: disposition; step 2: cognitive factors; step 3: patient-practitioner
      relationship) and adherence to HRE as the dependent variable was conducted. The
      factors in step 3 were the most significant and explained 16% (p < 0.001) of the
      variance in adherence to HRE. In addition, a high score for patient neuroticism
      was found to correlate with poor adherence to HRE. CONCLUSION: These preliminary
      results suggest that the patient-practitioner relationship is the best predictor
      of adherence to HRE, and that improving patient perception of the clinician's
      productivity, communication of information and trust during consultations may
      improve adherence to HRE.

PMID- 24322561
TI  - Potentiometric urea biosensor based on an immobilised fullerene-urease bio
      conjugate.
AB  - A novel method for the rapid modification of fullerene for subsequent enzyme
      attachment to create a potentiometric biosensor is presented. Urease was
      immobilized onto the modified fullerene nanomaterial. The modified fullerene
      immobilized urease (C60-urease) bioconjugate has been confirmed to catalyze the
      hydrolysis of urea in solution. The biomaterial was then deposited on a screen
      printed electrode containing a non-plasticized poly(n-butyl acrylate) (PnBA)
      membrane entrapped with a hydrogen ionophore. This pH-selective membrane is
      intended to function as a potentiometric urea biosensor with the deposition of
      C60-urease on the PnBA membrane. Various parameters for fullerene modification
      and urease immobilization were investigated. The optimal pH and concentration of
      the phosphate buffer for the urea biosensor were 7.0 and 0.5 mM, respectively.
      The linear response range of the biosensor was from 2.31 * 10-3 M to 8.28 * 10-5
      M. The biosensor's sensitivity was 59.67 +/- 0.91 mV/decade, which is close to
      the theoretical value. Common cations such as Na+, K+, Ca2+, Mg2+ and NH4+ showed
      no obvious interference with the urea biosensor's response. The use of a
      fullerene-urease bio-conjugate and an acrylic membrane with good adhesion
      prevented the leaching of urease enzyme and thus increased the stability of the
      urea biosensor for up to 140 days. 

PMID- 24322563
TI  - Design and evaluation of a low-cost smartphone pulse oximeter.
AB  - Infectious diseases such as pneumonia take the lives of millions of children in
      low- and middle-income countries every year. Many of these deaths could be
      prevented with the availability of robust and low-cost diagnostic tools using
      integrated sensor technology. Pulse oximetry in particular, offers a unique non
      invasive and specific test for an increase in the severity of many infectious
      diseases such as pneumonia. If pulse oximetry could be delivered on widely
      available mobile phones, it could become a compelling solution to global health
      challenges. Many lives could be saved if this technology was disseminated
      effectively in the affected regions of the world to rescue patients from the
      fatal consequences of these infectious diseases. We describe the implementation
      of such an oximeter that interfaces a conventional clinical oximeter finger
      sensor with a smartphone through the headset jack audio interface, and present a
      simulator-based systematic verification system to be used for automated
      validation of the sensor interface on different smartphones and media players. An
      excellent agreement was found between the simulator and the audio oximeter for
      both oxygen saturation and heart rate over a wide range of optical transmission
      levels on 4th and 5th generations of the iPod TouchTM and iPhoneTM devices. 

PMID- 24322567
TI  - Perceived risk following melanoma genetic testing: a 2-year prospective study
      distinguishing subjective estimates from recall.
AB  - A major goal of predictive genetic testing is to alert people to their risk
      before illness onset; however, little is known about how risk perceptions change
      following genetic testing and whether information is recalled accurately over
      time. In the United States, a CDKN2A/p16 mutation confers 76 % lifetime risk of
      melanoma. Following genetic counseling and test reporting, subjective risk
      estimates and recall of counselor-provided risk estimates were assessed 5 times
      over the next 2 years among 60 adult members of 2 extended CDKN2A/p16 kindreds.
      No sustained changes from baseline in risk perceptions were reported. Unaffected
      carriers (n = 15) consistently reported significantly lower subjective risk
      estimates (46 %) than they were actually given (76 %, p < 0.001) or recalled
      having been given (60 %, p < 0.001). Noncarriers' (n = 27) risk estimates
      decreased following results disclosure, but rebounded, with both subjective and
      recalled estimates subsequently exceeding what they were told by the counselor
      (both ps < 0.001). Affected carriers' (n = 18) risk estimates for developing a
      new melanoma corresponded well to counselor-provided information (p = 0.362). For
      all 3 patient groups, results were consistent across multiple risk measures and
      remained similar when demographic, phenotypic, and baseline behavioral
      contributors to melanoma risk were statistically controlled. These findings are
      consistent with other studies of risk perception, but additional studies of more
      diverse populations are needed to understand the reasons behind both the
      persistence of initial risk estimates and their divergence from information
      provided by the counselor during genetic counseling. Additionally, determining
      whether holding subjective risk perceptions that differ from counselor-provided
      information ultimately affects adherence to management recommendations will help
      guide the presentation of risk information in genetic counseling practice. 

PMID- 24322568
TI  - Spatially resolved single photon detection with a quantum sensor array.
AB  - We propose a method of resolving a spatially coherent signal, which contains on
      average just a single photon, against the background of local noise at the same
      frequency. The method is based on detecting the signal simultaneously in several
      points more than a wavelength apart through the entangling interaction of the
      incoming photon with the quantum metamaterial sensor array. The interaction
      produces the spatially correlated quantum state of the sensor array,
      characterised by a collective observable (e.g., total magnetic moment), which is
      read out using a quantum nondemolition measurement. We show that the effects of
      local noise (e.g., fluctuations affecting the elements of the array) are
      suppressed relative to the signal from the spatially coherent field of the
      incoming photon as , where N is the number of array elements. The realisation of
      this approach in the microwave range would be especially useful and is within the
      reach of current experimental techniques. 

PMID- 24322570
TI  - Elective use of supraglottic airway devices for primary airway management in
      children with difficult airways.
AB  - BACKGROUND: Supraglottic airways (SGAs) have an established role in airway
      management of difficult airways in both adults and children. However, there are
      limited data regarding the use of SGAs for primary airway management in children.
      The aim of this study is to assess the success rates and adverse events related
      to the use of SGAs for primary airway management during anaesthesia in children
      with difficult airways. METHODS: A retrospective analysis of SGA use for primary
      airway management in the difficult airway population in a single centre over a 4
      yr period was performed. Difficult airway was defined as either a history of
      difficult direct laryngoscopy (a documented Cormack and Lehane Grade 3 or greater
      and the need for an alternate device to direct laryngoscopy for successful
      tracheal intubation), a history of difficult mask ventilation, or both. The
      difficult airway condition, patient characteristic data, type and length of
      procedure, type and size of SGA placed, number of attempts for successful device
      placement, success/failure associated with the device during anaesthetic
      maintenance, and complications were recorded. RESULTS: A total of 77,272 children
      received general anaesthesia in a free-standing paediatric institution. Four
      hundred and fifty-nine patients were reported to have a difficult airway. Of
      those, 109 received general anaesthesia and an SGA for primary management,
      meeting the inclusion criteria for this study during a 4-yr period. An SGA was
      successfully used in 96% of these patients. In four patients, an alternative
      airway was needed. CONCLUSIONS: SGAs can be effectively utilized for airway
      maintenance in the paediatric difficult airway population.

PMID- 24322569
TI  - Overdiagnosis in low-dose computed tomography screening for lung cancer.
AB  - IMPORTANCE: Screening for lung cancer has the potential to reduce mortality, but
      in addition to detecting aggressive tumors, screening will also detect indolent
      tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases
      represent an important potential harm of screening because they incur additional
      cost, anxiety, and morbidity associated with cancer treatment. OBJECTIVE: To
      estimate overdiagnosis in the National Lung Screening Trial (NLST). DESIGN,
      SETTING, AND PARTICIPANTS: We used data from the NLST, a randomized trial
      comparing screening using low-dose computed tomography (LDCT) vs chest
      radiography (CXR) among 53 452 persons at high risk for lung cancer observed for
      6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the
      NLST compared with the CXR arm. MAIN OUTCOMES AND MEASURES: We calculated 2
      measures of overdiagnosis: the probability that a lung cancer detected by
      screening with LDCT is an overdiagnosis (PS), defined as the excess lung cancers
      detected by LDCT divided by all lung cancers detected by screening in the LDCT
      arm; and the number of cases that were considered overdiagnosis relative to the
      number of persons needed to screen to prevent 1 death from lung cancer. RESULTS:
      During follow-up, 1089 lung cancers were reported in the LDCT arm and 969 in the
      CXR arm of the NLST. The probability is 18.5% (95% CI, 5.4%-30.6%) that any lung
      cancer detected by screening with LDCT was an overdiagnosis, 22.5% (95% CI, 9.7%
      34.3%) that a non-small cell lung cancer detected by LDCT was an overdiagnosis,
      and 78.9% (95% CI, 62.2%-93.5%) that a bronchioalveolar lung cancer detected by
      LDCT was an overdiagnosis. The number of cases of overdiagnosis found among the
      320 participants who would need to be screened in the NLST to prevent 1 death
      from lung cancer was 1.38. CONCLUSIONS AND RELEVANCE: More than 18% of all lung
      cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis
      should be considered when describing the risks of LDCT screening for lung cancer.

PMID- 24322571
TI  - Prediction of immediate postoperative pain using the analgesia/nociception index:
      a prospective observational study.
AB  - BACKGROUND: The analgesia/nociception index (ANI) is derived from heart rate
      variability, ranging from 0 (maximal nociception) to 100 (maximal analgesia), to
      reflect the analgesia/nociception balance during general anaesthesia. This should
      be correlated with immediate postoperative pain in the post-anaesthesia care unit
      (PACU). The aim of this study was to evaluate the performance of ANI measured at
      arousal from general anaesthesia to predict immediate postoperative pain on
      arrival in PACU. METHODS: Two hundred patients undergoing ear, nose, and throat
      or lower limb orthopaedic surgery with general anaesthesia using an inhalational
      agent and remifentanil were included in this prospective observational study. The
      ANI was measured immediately before tracheal extubation and pain intensity was
      assessed within 10 min of arrival in PACU using a 0-10 numerical rating scale
      (NRS). The relationship between ANI and NRS was assessed using linear regression.
      A receiver-operating characteristic (ROC) curve was used to evaluate the
      performance of ANI to predict NRS>3. RESULTS: A negative linear relationship was
      observed between ANI immediately before extubation and NRS on arrival in PACU.
      Using a threshold of <50, the sensitivity and specificity of ANI to discriminate
      between patients with NRS<=3 and NRS>3 were both 86% with 92% negative predictive
      value, corresponding to an area under the ROC curve of 0.89. CONCLUSIONS: The
      measurement of ANI immediately before extubation after inhalation-remifentanil
      anaesthesia was significantly associated with pain intensity on arrival in PACU.
      The performance of ANI for the prediction of immediate postoperative pain is good
      and may assist physicians in optimizing acute pain management. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01796249.

PMID- 24322572
TI  - Randomized controlled trial of the effect of depth of anaesthesia on
      postoperative pain.
AB  - BACKGROUND: Our hypothesis was that deep anaesthesia, as estimated by a low
      target bispectral index (BIS) of 30-40, would result in less postoperative pain
      than that achieved at a conventional depth of anaesthesia. METHODS: We undertook
      a randomized double-blind controlled study at two tertiary teaching hospitals in
      New Zealand (2010-1) recruiting 135 adult patients ASA I-II presenting for non
      emergent surgery under general anaesthesia requiring tracheal intubation.
      Anaesthesia was maintained with desflurane and a multimodal analgesia regimen
      comprising fentanyl infusion, i.v. paracetamol, and parecoxib. Patients were
      randomly assigned to either a low BIS (30-40) group or a high BIS (45-60) group.
      Desflurane concentrations were titrated to achieve these targets. Postoperative
      pain was assessed by: the pain on awakening (0-10, verbal rating scale,
      VRS(awake)) in the post-anaesthetic care unit; pain on activity at 20-24 h after
      operation (VRS(d1A)); and the rate of morphine patient-controlled analgesia (PCA)
      usage over the first 24 h. RESULTS: There was no statistically significant
      difference between the two groups for any of the pain scores. The median [inter
      quartile range (IQR)] VRS(awake) was 4.0 (0-8) for the low and 4.0 (0-8) for the
      high BIS groups (P=0.56). The median (IQR) VRS(d1A) was 3.0 (1-5) for the low and
      3.0 (1.5-4.5) for the high BIS groups (P=0.83). The median PCA morphine
      consumption in the low BIS group was 0.61 mg h(-1) (0.04-1.5) vs 0.43 mg h(-1) (0
      1.59) in the high BIS group (P=0.98). CONCLUSIONS: We conclude that there is no
      clinically useful analgesic effect of a deep anaesthesia regimen.

PMID- 24322573
TI  - Cardiopulmonary exercise variables are associated with postoperative morbidity
      after major colonic surgery: a prospective blinded observational study.
AB  - BACKGROUND: Postoperative complications are associated with reduced fitness.
      Cardiopulmonary exercise testing (CPET) has been used in risk stratification. We
      investigated the relationship between preoperative CPET and in-hospital morbidity
      in major colonic surgery. METHODS: We prospectively studied 198 patients
      undergoing major colonic surgery (excluding neoadjuvant cancer therapy),
      performing preoperative CPET (reported blind to clinical state), and recording
      morbidity (assessed blind to CPET), postoperative outcome, and length of stay.
      RESULTS: Of 198 patients, 62 were excluded: 11 had emergency surgery, 25 had no
      surgery, 23 had incomplete data, and three were unable to perform CPET. One
      hundred and thirty-six (89 males, 47 females) were available for analysis. The
      median age was 71 [inter-quartile range (IQR) 62-77] yr. Sixty-five patients
      (48%) had a complication at day 5 after operation. Measurements significantly
      lower in patients with complications than those without were O2 uptake (VO2) at
      estimated lactate threshold (theta(L)) [median 9.9 (IQR 8.3-12.7) vs 11.2 (9.5
      14.2) ml kg(-1) min(-1), P<0.01], VO2 at peak [15.2 (12.6-18.1) vs 17.2 (13.7
      22.5) ml kg(-1) min(-1), P=0.01], and ventilatory equivalent for CO2 (V(E)/VCO2)
      at theta(L) [31.3 (28.0-34.8) vs 33.9 (30.0-39.1), P<0.01]. A final multivariable
      logistic regression model contained VO2 at theta(L) {one-point change odds ratio
      (OR) 0.77 [95% confidence interval (CI) 0.66-0.89], P<0.0005; two-point change OR
      0.61 (0.46-0.81) and gender [OR 4.42 (1.78-9.88), P=0.001]}, and was reasonably
      able to discriminate those with and without complications (AUC 0.71, CI 0.62
      0.80, 68% sensitivity, 65% specificity). CONCLUSIONS: CPET variables are
      associated with postoperative morbidity. A multivariable model with VO2 at
      theta(L) and gender discriminates those with complications after colonic surgery.

PMID- 24322574
TI  - Fibro-adipose vascular anomaly: clinical-radiologic-pathologic features of a
      newly delineated disorder of the extremity.
AB  - BACKGROUND: The diagnosis and management of vascular anomalies of the extremities
      can be challenging as these disorders are uncommon and may clinically overlap.
      The aim of this paper is to describe the clinical, radiologic, and
      histopathologic features of fibro-adipose vascular anomaly (FAVA), a previously
      unrecognized disorder of the limb. METHODS: The clinical, imaging, operative, and
      histopathologic data from patients with a unique intramuscular lesion of the
      extremities comprising dense fibrofatty tissue and slow-flow vascular
      malformations were retrospectively reviewed. RESULTS: Sixteen patients diagnosed
      with FAVA of the extremity (3 male and 13 female individuals) met the clinical,
      radiologic, and histopathologic inclusion criteria. The age at presentation
      ranged from the time of birth to 28 years. The locations of the lesions were:
      calf (n=10), forearm/wrist (n=3), and thigh (n=3). Fourteen patients presented
      with severe pain. Seven of the patients with calf lesions had limited ankle
      dorsiflexion. On imaging, the complex intramuscular lesions replaced muscle
      fibers with fibrofatty overgrowth and phlebectasia (dilation of the veins). The
      extrafascial component comprised fatty overgrowth, phlebectasia, and an
      occasional lymphatic malformation. The histopathologic features comprised dense
      fibrous tissue, fat, and lymphoplasmacytic aggregates within atrophied skeletal
      muscle. Adipose tissue also infiltrated skeletal muscle at the periphery of the
      lesion. There were large, irregular, and sometimes excessively muscularized
      venous channels and smaller, clustered channels. Other findings include
      organizing thrombi, a lymphatic component, and dense fibrous tissue-encircled
      nerves. CONCLUSIONS: The constellation of clinical, radiologic, and
      histopathologic features constitutes a distinct entity comprising fibrofatty
      infiltration of muscle, unusual phlebectasia with pain, and contracture of the
      affected extremity. The clinical and radiologic findings permit the diagnosis of
      FAVA with major therapeutic implications. LEVEL OF EVIDENCE: Level III.

PMID- 24322577
TI  - Mice are unable to endogenously regenerate podocytes during the repair of
      immunotoxin-induced glomerular injury.
AB  - BACKGROUND: Recent studies have reported that podocytes are postnatally generated
      from progenitor cells localized in Bowman's capsule or in the bone marrow. In the
      present study, we investigated whether or not podocyte regeneration is important
      in the repair of injured glomeruli after mild podocyte injury in mice. METHODS:
      Mild podocyte injury was induced in NEP25 mice (n = 8) by injecting an
      immunotoxin, LMB2 (0.625 ng/g body weight). Control mice, not injured by LMB2
      injection (n = 7) was used as a comparison. Proliferating cells were labeled by
      continuous infusion of bromodeoxyuridine (BrdU). Podocytes, identified by
      nephrin, WT1 or podocin staining, that had incorporated BrdU were enumerated 4
      weeks later. RESULTS: A total of 742 corpuscles were inspected in serial sections
      stained for BrdU and nephrin; 19% showed sclerosis. BrdU(+) cells were observed
      in both the glomeruli and Bowman's capsules, averaging 2.5 +/- 3.1 in non
      sclerotic corpuscles and 7.0 +/- 5.8 in sclerotic corpuscles. Only one BrdU(+)
      cell was also positive for nephrin. Another cell, localized at a position
      consistent with its potential identification as a podocyte, was nephrin negative
      but had incorporated BrdU. WT1 staining similarly revealed that only two nuclei
      were doubly positive for BrdU and WT1. Additional 1676 corpuscles were inspected
      by double staining for BrdU and podocin; none were doubly positive. CONCLUSIONS:
      Podocytes are not replenished by proliferation of endogenous progenitor cells in
      mice with glomerular injury.

PMID- 24322575
TI  - Respiratory motion correction in dynamic MRI using robust data decomposition
      registration - application to DCE-MRI.
AB  - Motion correction in Dynamic Contrast Enhanced (DCE-) MRI is challenging because
      rapid intensity changes can compromise common (intensity based) registration
      algorithms. In this study we introduce a novel registration technique based on
      robust principal component analysis (RPCA) to decompose a given time-series into
      a low rank and a sparse component. This allows robust separation of motion
      components that can be registered, from intensity variations that are left
      unchanged. This Robust Data Decomposition Registration (RDDR) is demonstrated on
      both simulated and a wide range of clinical data. Robustness to different types
      of motion and breathing choices during acquisition is demonstrated for a variety
      of imaged organs including liver, small bowel and prostate. The analysis of
      clinically relevant regions of interest showed both a decrease of error (15-62%
      reduction following registration) in tissue time-intensity curves and improved
      areas under the curve (AUC60) at early enhancement. 

PMID- 24322578
TI  - Glucose-lowering drugs in patients with chronic kidney disease: a narrative
      review on pharmacokinetic properties.
AB  - The achievement of a good glycaemic control is one of the cornerstones for
      preventing and delaying progression of microvascular and macrovascular
      complications in patients with both diabetes and chronic kidney disease (CKD). As
      for other drugs, the presence of an impaired renal function may significantly
      affect pharmacokinetics of the majority of glucose-lowering agents, thus exposing
      diabetic CKD patients to a higher risk of side effects, mainly hypoglycaemic
      episodes. As a consequence, a reduction in dosing and/or frequency of
      administration is necessary to keep a satisfactory efficacy/safety profile. In
      this review, we aim to summarize the pharmacology of the most widely used glucose
      lowering agents, discuss whether and how it is altered by a reduced renal
      function, and the recommendations that can be made for their use in patients with
      different degrees of CKD. 

PMID- 24322579
TI  - Two-times weekly hemodialysis in China: frequency, associated patient and
      treatment characteristics and Quality of Life in the China Dialysis Outcomes and
      Practice Patterns study.
AB  - BACKGROUND: Renal replacement therapy is rapidly expanding in China, and two
      times weekly dialysis is common, but detailed data on practice patterns are
      currently limited. Using cross-sectional data from the China Dialysis Outcomes
      and Practice Patterns Study (DOPPS), we describe the hemodialysis practice in
      China compared with other DOPPS countries, examining demographic, social and
      clinical characteristics of patients on two-times weekly dialysis. METHODS: The
      DOPPS protocol was implemented in 2011 among a cross-section of 1379 patients in
      45 facilities in Beijing, Guangzhou and Shanghai. Data from China were compared
      with a cross section of 11 054 patients from the core DOPPS countries (collected
      2009-11). Among China DOPPS patients, logistic and linear regression were used to
      describe the association of dialysis frequency with patient and treatment
      characteristics and quality of life. RESULTS: A total of 26% of the patients in
      China were dialyzing two times weekly, compared with < 5% in other DOPPS regions.
      Standardized Kt/V was lowest in China (2.01) compared with other regions (2.12
      2.27). Female sex, shorter dialysis vintage, lower socioeconomic status, less
      health insurance coverage, and lack of diabetes and hypertension were associated
      with dialyzing two times weekly (versus three times weekly). Patients dialyzing
      two times per week had longer treatment times and lower standardized Kt/V, but
      similar quality of life scores. CONCLUSIONS: Two-times weekly dialysis is common
      in China, particularly among patients, who started dialysis more recently, have a
      lower comorbidity burden and have financial constraints. Quality of life scores
      do not differ between the two-times and three-times weekly groups. The effect on
      clinical outcomes merits further study.

PMID- 24322580
TI  - Cognitive mechanisms of change in multidisciplinary treatment of patients with
      chronic widespread pain: a prospective cohort study.
AB  - OBJECTIVE: To evaluate the contribution of improvement in negative emotional
      cognitions, active cognitive coping, and control and chronicity beliefs to the
      outcome of multidisciplinary treatment in patients with chronic widespread pain.
      DESIGN: Prospective cohort study. PATIENTS: A total of 120 subjects diagnosed
      with chronic widespread pain, who completed a multidisciplinary pain programme.
      METHODS: Data from baseline, 6 months and 18 months follow-up measurements were
      analysed. Longitudinal relationships were analysed between changes in cognitions
      and outcome, using generalized estimated equations. Outcome domains included:
      pain, interference of pain in daily life, depression, and global perceived
      effect. Cognitive domains included: negative emotional cognitions, active
      cognitive coping and control and chronicity beliefs. RESULTS: Improvements in
      negative emotional cognitions were associated with improvements in all outcome
      domains, in particular with improvement in interference of pain with daily life
      and depression (between baseline and 6 months, and 6 and 18 months). Improvements
      in active cognitive coping were associated with improvements in interference of
      pain in daily life (between baseline and 6 months). Improvements in control and
      chronicity beliefs were associated with improvements in pain and depression
      (between 6 and 18 months). CONCLUSION: Improvement in negative emotional
      cognitions seems to be a key mechanism of change in multidisciplinary treatment
      of chronic widespread pain. Improvement in active cognitive coping and
      improvement in control and chronic timeline beliefs may also constitute
      mechanisms of change, although the evidence is less strong.

PMID- 24322581
TI  - Helicene-grafted vinyl- and carbene-osmium complexes: an example of acid-base
      chiroptical switching.
AB  - The first helicene-based carbene-osmium complex has been prepared from a vinyl
      osmium derivative and this system has been shown to behave as a potential acid
      base triggered chiroptical switch. 

PMID- 24322582
TI  - Analysis of the relationship between different bleeding positions on
      intraoperative rupture anterior circulation aneurysm and surgical treatment
      outcome.
AB  - BACKGROUND: It is well recognized that intraoperative aneurysm rupture (IAR) is a
      serious event that is difficult to manage and has a relatively serious influence
      on a patient's prognosis. The aim of this study was to evaluate the prognostic
      value of different bleeding positions of IAR in patients, and to describe the
      technique that the authors have used to clip the ruptured aneurysms. METHODS:
      From May 2009 to March 2012, a total of 148 aneurysms in 135 consecutive patients
      in our institution underwent clipping surgeries, and 31 IARs occurred in 30
      patients. The clinical data of all patients were retrospectively analyzed.
      Statistics analysis was performed to analyze possible factors of different
      bleeding positions of IARs, to assist observation. RESULTS: Outcome was estimated
      by Glasgow outcome scale via following up or calling back within 1, 3, and 6
      months after surgery: 94 patients were 5', 23 patients were 4', nine patients
      were 3', two patients were 2' and eight patients were 1'. There was no
      significant difference between the outcome of IAR and that of no intraoperative
      aneurysm rupture (NIAR) in Hunt-Hess groups 0-III (P = 0.802) and Hunt-Hess
      groups IV-V (P = 0.229), and the different bleeding positions were shown to be an
      important factor that significantly influences the patients' prognosis (P =
      0.001). CONCLUSIONS: Different bleeding positions of IAR have a significant
      impact on surgical outcome; IAR of the neck is the most devastating complication.
      If surgeons take appropriate measures according to different bleeding positions,
      the efficiency, accuracy and security of the operation will be improved.

PMID- 24322583
TI  - Anterior clinoidectomy.
AB  - BACKGROUND: The optic nerve within the optic canal, the parophthalmic segment of
      the carotid artery, and the oculomotor nerve in the superior orbital fissure all
      lay against the anterior clinoid process. Bone resection uncovers these
      structures. METHOD: For extradural resection of the anterior clinoid process and
      surrounding bone, two key steps are recommended: bony opening of the superior
      orbital fissure, and transection of the orbitotemporal periosteal fold.
      CONCLUSION: Anterior clinoidectomy is technically challenging. Following a
      sequence of surgical steps to expose clearly-defined surgical landmarks helps to
      make this procedure simple and safe. KEY POINTS: * Pterional craniotomy *
      Complete extradural anterior clinoidectomy * Slit dura (3 mm) to drain
      cerebrospinal fluid * Peel dura from orbital roof and lateral wall * Bony opening
      of superior orbital fissure to use it as surgical corridor * Drilling of optic
      canal * Transection of orbitotemporal periosteal fold * Hollow anterior clinoid
      process and piece-meal resection * Transection of falciforme ligament to free
      optic nerve * Replace falciforme ligament by extradural free pericranial flap.

PMID- 24322584
TI  - Clinical characteristics and surgical outcomes of spinal intramedullary ependymal
      cysts.
AB  - OBJECT: Intramedullary ependymal cysts are exceedingly rare lesions, and have
      been previously reported in the literature as case reports. The aim of this study
      was to discuss the clinical presentation and the outcomes of microsurgery for
      these benign lesions. METHODS: The authors retrospectively reviewed the records
      of ten patients who underwent microsurgery for intramedullary ependymal cysts.
      All patients had preoperative and postoperative magnetic resonance imaging. The
      surgical treatment included gross total resection and biopsy plus a cyst
      subarachnoid shunt. The diagnosis of intramedullary ependymal cysts was based on
      radiological and pathological criteria. All patients were followed up, with a
      mean duration of 47.6 months. RESULTS: Intramedullary ependymal cysts were
      hypointense on T1-weighted images and hyperintense on T2-weighted images.
      Contrast-enhanced T1-weighted images showed no enhancement. Gross total resection
      was achieved in one case. Biopsy of the cyst wall plus cyst-subarachnoid shunt
      placement was achieved in nine cases. Long-term neurological function was
      improved in eight patients. No recurrence was observed on magnetic resonance
      imaging. CONCLUSIONS: Ependymal cysts should be considered in the differential
      diagnosis of intramedullary cysts. For symptomatic patients, early surgery should
      be performed before neurological deficits deteriorate. Complete decompression and
      cyst-subarachnoid shunt placement is the optimal treatment and the outcome may be
      favorable.

PMID- 24322585
TI  - Brainstem surgery assisted by temporary trans-venous pacing to prevent severe
      bradycardia.

PMID- 24322586
TI  - The wheat HMW-glutenin 1Dy10 gene promoter controls endosperm expression in
      Brachypodium distachyon.
AB  - The grass species Brachypodium distachyon has emerged as a model system for the
      study of gene structure and function in temperate cereals. As a first
      demonstration of the utility of Brachypodium to study wheat gene promoter
      function, we transformed it with a T-DNA that included the uidA reporter gene
      under control of a wheat High-Molecular-Weight Glutenin Subunit (HMW-GS) gene
      promoter and transcription terminator. For comparison, the same expression
      cassette was introduced into wheat by biolistics. Histochemical staining for beta
      glucuronidase (GUS) activity showed that the wheat promoter was highly expressed
      in the endosperms of all the seeds of Brachypodium and wheat homozygous plants.
      It was not active in any other tissue of transgenic wheat, but showed variable
      and sporadic activity in a minority of styles of the pistils of four homozygous
      transgenic Brachypodium lines. The ease of obtaining transgenic Brachypodium
      plants and the overall faithfulness of expression of the wheat HMW-GS promoter in
      those plants make it likely that this model system can be used for studies of
      other promoters from cereal crop species that are difficult to transform. 

PMID- 24322587
TI  - Cholinergic neuromuscular transmission mediated by interstitial cells of Cajal in
      the myenteric layer in mouse ileal longitudinal smooth muscles.
AB  - To elucidate the roles played by the interstitial cells of Cajal in the myenteric
      layer (ICC-MY) in cholinergic neuromuscular transmission, we recorded mechanical
      and electrical activities in response to electrical field stimulation (EFS) of
      the ileal longitudinal muscle strips from WBB6F1-W/W(V) (W/W(V)) mutant mice,
      that lacked ICC-MY and compared with those in WBB6F1-+/+ (+/+) control mice. In
      +/+ muscle strips, EFS induced phasic contractions, which were abolished or
      strongly attenuated by atropine or tetrodotoxin. In W/W(V) preparations, EFS
      induced similar phasic contractions, but the cholinergic component was smaller
      than that in +/+ strips. This was despite of the fact that the contractions
      because of exogenous applications of carbachol and high K(+) solution in W/W(V)
      strips were comparable to or rather greater than those in the +/+ preparations.
      EFS induced atropine-sensitive excitatory junction potentials (EJPs) in the +/+
      longitudinal smooth muscle cells but not in W/W(V) cells. In the presence of
      eserine, EFS induced atropine-sensitive EJPs in W/W(V) cells. These results
      suggest that ICC-MY mediate the cholinergic neuromuscular transmission in mouse
      ileal longitudinal smooth muscles. In addition, the other pathway in which ICC-MY
      are not involved can operate concomitantly. 

PMID- 24322590
TI  - Constitutive modeling of pia-arachnoid complex.
AB  - The pia-arachnoid complex (PAC) covering the brain plays an important role in the
      mechanical response of the brain during impact or inertial loading. Recent
      studies have revealed the complicated material behavior of the PAC. In this
      study, the nonlinear viscoelastic, transversely isotropic material properties of
      the PAC were modeled as Mooney-Rivlin ground substance with collagen fibers
      strengthening within the meningeal plane through an exponential model. The
      material constants needed were determined using experimental data from in-plane
      tension, normal traction, and shear tests conducted on bovine specimens. Results
      from this study provide essential information to properly model the PAC membrane,
      an important component in the skull/brain interface, in a computational brain
      model. Such an improved representation of the skull/brain interface will enhance
      the accuracy of finite element models used in brain injury mechanism studies
      under various loading conditions. 

PMID- 24322591
TI  - Endothelial insulin-like growth factor-1 modulates proliferation and phenotype of
      smooth muscle cells induced by low shear stress.
AB  - Endothelial cells (ECs) are directly exposed to shear stress and modulate the
      neighboring vascular smooth muscle cells (VSMCs), which plays important roles in
      vascular remodeling during atherosclerosis. Our previous research revealed that
      insulin-like growth factors (IGFs) might participate in low shear stress (LowSS)
      induced vascular remodeling, which remains to be elucidated. Using EC/VSMC co
      cultured parallel-plate flow chamber, LowSS (5 dyn/cm(2)) was applied and normal
      shear stress (NSS, 15 dyn/cm(2)) was used as control. LowSS induced IGF-1
      secretion from ECs, which subsequently phosphorylated IGF-1 receptor (IGF-1R) on
      co-cultured VSMCs, then increased Akt phosphorylation and Sirt2 expression.
      Decreasing IGF-1 in ECs by RNA interference (RNAi) reversed these effects on
      VSMCs. Exogenous IGF-1 increased IGF-1R and Akt phosphorylation, Sirt2
      expression, and proliferation of VSMCs, and induced VSMCs towards synthetic
      phenotype. PI3 K/Akt specific inhibitor wortmannin decreased Sirt2 expression,
      proliferation, and synthetic phenotype transformation of VSMCs, but had no effect
      on IGF-1R. Sirt2 RNAi repressed VSMC proliferation and phenotypic transformation,
      but had no effect on IGF-1R and Akt. Taken together, LowSS induces the secretion
      of IGF-1 from ECs, which subsequently paracrine influences the co-cultured VSMCs
      via IGF-1R and Akt phosphorylation, and Sirt2 expression, then results in the
      proliferation and synthetic phenotype transformation. 

PMID- 24322592
TI  - Time to manage Mycoplasma genitalium as an STI: but not with azithromycin 1 g!
AB  - PURPOSE OF REVIEW: Mycoplasma genitalium is a sexually transmitted infection that
      causes significant morbidity in men and women and is a co-factor in HIV
      transmission. However, commercial diagnostic tests are not generally available
      for M. genitalium and sub-optimal treatment is often given. We review the
      literature on the burden of infection, how it may present in clinical practice
      and the effectiveness of current treatment regimens. RECENT FINDINGS: In-vivo and
      in-vitro data strongly suggest that M. genitalium is an important cause of
      urethritis, cervicitis, pelvic inflammatory disease and potentially asymptomatic
      proctitis. Studies now consistently demonstrate suboptimal eradication rates with
      the current treatment regimens recommended first line for the treatment of
      nongonococcal urethritis. Concurrently, there has been a rapid emergence of
      antibiotic resistance in M. genitalium, with macrolide resistance now appearing
      to be endemic in some centres, and quinolone resistance is beginning to emerge.
      SUMMARY: In the absence of specific M. genitalium diagnostic and antimicrobial
      resistance testing, azithromycin 1 g should not be used for the management of
      patients with symptomatic disease potentially caused by M. genitalium. This
      review offers an alternative evidence-based approach to managing such patients
      that should, theoretically, reduce the risk of the development of antimicrobial
      resistance.

PMID- 24322593
TI  - Optimizing antiretroviral therapy for women living with HIV.
AB  - PURPOSE OF REVIEW: This review considers the evidence available to guide
      clinicians in their choice of optimal antiretroviral therapy (ART) for women with
      HIV. RECENT FINDINGS: Cohort and clinical trial data indicate that ART is as
      efficacious in women as men, although women are more likely to discontinue
      therapy, which compromises effectiveness. For many drugs, women have higher
      plasma levels than men, although whether this is secondary to differing
      metabolism in women or because on average women have a lower body mass than men
      is not clear. For many drugs, women experience more adverse events secondary to
      ART. Opinion on the use of efavirenz in pregnancy differs between countries. The
      average age of women with HIV is increasing. Although virological responses to
      ART are not affected by age, immunological responses may be poorer. Older women
      with HIV face issues such as neurocognitive impairment, early menopause,
      osteoporosis and polypharmacy, which will have the potential to impact on their
      use of ART. SUMMARY: When planning ART regimes with women, clinicians need to be
      mindful of the woman's social situation and stage in the life course, as well as
      the scientific data on individual drug effectiveness according to sex.

PMID- 24322588
TI  - Mechanisms of acupuncture-electroacupuncture on persistent pain.
AB  - In the last decade, preclinical investigations of electroacupuncture mechanisms
      on persistent tissue injury (inflammatory), nerve injury (neuropathic), cancer,
      and visceral pain have increased. These studies show that electroacupuncture
      activates the nervous system differently in health than in pain conditions,
      alleviates both sensory and affective inflammatory pain, and inhibits
      inflammatory and neuropathic pain more effectively at 2 to 10 Hz than at 100 Hz.
      Electroacupuncture blocks pain by activating a variety of bioactive chemicals
      through peripheral, spinal, and supraspinal mechanisms. These include opioids,
      which desensitize peripheral nociceptors and reduce proinflammatory cytokines
      peripherally and in the spinal cord, and serotonin and norepinephrine, which
      decrease spinal N-methyl-D-aspartate receptor subunit GluN1 phosphorylation.
      Additional studies suggest that electroacupuncture, when combined with low
      dosages of conventional analgesics, provides effective pain management which can
      forestall the side effects of often-debilitating pharmaceuticals. 

PMID- 24322594
TI  - Sexually transmitted infections: controversies and conundrums in screening,
      treatment and stigma.

PMID- 24322596
TI  - Controversies on the origin of proliferating epithelial cells after kidney
      injury.
AB  - The kidney possesses the capacity to repair after an acute insult, even one that
      causes complete organ failure. This regenerative response is characterized by
      robust proliferation of epithelial cells, principally those located in the
      proximal tubule. Because defining the origin of these reparative cells has
      important consequences for stem cell and regenerative approaches to treating
      kidney injury, this area has been the subject of intense investigation and
      debate. While progress has been made in narrowing the possible origin of these
      cells to an intratubular source, there has been no consensus between the
      possibility of a pre-existing intratubular stem or progenitor cell versus the
      possibility that fully differentiated epithelial cells re-enter the cell cycle
      after injury and generate new proximal tubule cells through self-duplication.
      This review will summarize the evidence on both sides of this active controversy
      and provide support for the notion that no pre-existing proximal tubule stem cell
      population exists, but rather all differentiated proximal tubule epithelia have
      the capacity to proliferate during repair by a mechanism of dedifferentiation and
      self-duplication. 

PMID- 24322595
TI  - Rates of complications and mortality in older patients with diabetes mellitus:
      the diabetes and aging study.
AB  - IMPORTANCE: In the coming decades, the population of older adults with type 2
      diabetes mellitus is expected to grow substantially. Understanding the clinical
      course of diabetes in this population is critical for establishing evidence-based
      clinical practice recommendations, identifying research priorities, allocating
      resources, and setting health care policies. OBJECTIVE To contrast the rates of
      diabetes complications and mortality across age and diabetes duration categories.
      DESIGN, SETTING, AND PARTICIPANTS: This cohort study (2004-2010) included 72,310
      older (>= 60 years) patients with type 2 diabetes enrolled in a large, integrated
      health care delivery system. Incidence densities (events per 1000 person-years)
      were calculated for each age category (60-69, 70-79, and >= 80 years) and
      duration of diabetes (shorter [0-9 years] vs longer [>= 10 years]). MAIN OUTCOMES
      AND MEASURES: Incident acute hyperglycemic events, acute hypoglycemic events
      (hypoglycemia), microvascular complications (end-stage renal disease, peripheral
      vascular disease, lower limb amputation, and diabetic eye disease),
      cardiovascular complications (coronary artery disease, cerebrovascular disease,
      and congestive heart failure), and all-cause mortality. RESULTS: Among older
      adults with diabetes of short duration, cardiovascular complications followed by
      hypoglycemia were the most common nonfatal complications. For example, among
      individuals aged 70 to 79 years with a short duration of diabetes, coronary
      artery disease and hypoglycemia rates were higher (11.47 per 1000 person-years
      and 5.03 per 1000 person-years, respectively) compared with end-stage renal
      disease (2.60 per 1000 person-years), lower limb amputation (1.28 per 1000 person
      years), and acute hyperglycemic events (0.82 per 1000 person-years). We observed
      a similar pattern among patients in the same age group with a long duration of
      diabetes, with some of the highest incidence rates in coronary artery disease and
      hypoglycemia (18.98 per 1000 person-years and 15.88 per 1000 person-years,
      respectively) compared with end-stage renal disease (7.64 per 1000 person-years),
      lower limb amputation (4.26 per 1000 person-years), and acute hyperglycemic
      events (1.76 per 1000 person-years). For a given age group, the rates of each
      outcome, particularly hypoglycemia and microvascular complications, increased
      dramatically with longer duration of the disease. However, for a given duration
      of diabetes, rates of hypoglycemia, cardiovascular complications, and mortality
      increased steeply with advancing age, and rates of microvascular complications
      remained stable or declined. CONCLUSIONS AND RELEVANCE: Duration of diabetes and
      advancing age independently predict diabetes morbidity and mortality rates. As
      long-term survivorship with diabetes increases and as the population ages, more
      research and public health efforts to reduce hypoglycemia will be needed to
      complement ongoing efforts to reduce cardiovascular and microvascular
      complications.

PMID- 24322597
TI  - Preliminary results of the in vivo and in vitro characterization of a tentacle
      venom fraction from the jellyfish Aurelia aurita.
AB  - The neurotoxic effects produced by a tentacle venom extract and a fraction were
      analyzed and correlated by in vivo and in vitro approaches. The tentacle venom
      extract exhibited a wide range of protein components (from 24 to >225 kDa) and
      produced tetanic reactions, flaccid paralysis, and death when injected into
      crabs. Two chromatography fractions also produced uncontrolled appendix movements
      and leg stretching. Further electrophysiological characterization demonstrated
      that one of these fractions potently inhibited ACh-elicited currents mediated by
      both vertebrate fetal and adult muscle nicotinic acetylcholine receptors (nAChR)
      subtypes. Receptor inhibition was concentration-dependent and completely
      reversible. The calculated IC(50) values were 1.77 MUg/MUL for fetal and 2.28
      MUg/MUL for adult muscle nAChRs. The bioactive fraction was composed of a major
      protein component at ~90 kDa and lacked phospholipase A activity. This work
      represents the first insight into the interaction of jellyfish venom components
      and muscle nicotinic receptors.

PMID- 24322598
TI  - Breast cancer: updated guideline recommendations for HER2 testing.
AB  - The recently updated HER2 testing guidelines by ASCO and the College of American
      Pathologists (CAP) are a significant step towards personalized medicine. It is
      excellent news that such great effort has been put into standardizing biomarker
      assessment. Undoubtedly, these recommendations will improve the analytical
      validity of HER2 testing, its clinical utility and the communication among health
      care providers.

PMID- 24322599
TI  - Korean American women's perceptions about physical examinations and cancer
      screening services offered in Korea: the influences of medical tourism on Korean
      Americans.
AB  - Cancer is the leading cause of death for Korean-Americans (KAs), while cancer
      screening rates among KAs have been consistently low. Seven semi-structured focus
      group interviews with 34 KA women aged 40 or older in the Washington, DC
      metropolitan area were conducted to explore the perceptions of KA women about
      seeking physical examinations and cancer screening services in Korea. Data were
      analyzed using a framework approach. Informants positively perceived the use of
      health screening services in Korea in comparison to seeking such services in the
      US. Decision-making factors included cost benefits, high quality services, and
      more convenient screening procedures in Korea. These benefits outweighed the
      risks of delaying health care and travelling a vast distance with incurring
      additional travel costs. Motivations to seek these services in Korea included
      opportunities to visit their homeland and to enjoy comfortable communication with
      their native language. The increase of available information about Korean medical
      services due to the industry's aggressive marketing/PR was identified as a
      facilitator. Most informants did not recognize possible negative health outcomes
      of obtaining services in Korea such as inappropriate follow up care if having
      abnormal findings. Educational programs are needed to educate KAs about the
      benefits and risks of getting the services in Korea and proper follow up care in
      the US. Health care providers need to know the different cancer risks and
      screening needs for this population.

PMID- 24322600
TI  - Low compliance with iron-folate supplementation among postpartum mothers of
      Nepal: an analysis of Nepal Demographic and Health Survey 2011.
AB  - One in five maternal deaths are directly attributable to anaemia in the world.
      The World Health Organization recommends iron supplementation from the second
      trimester of pregnancy to 45 days after delivery. The aim of this study was to
      determine the compliance rate of iron-folate consumption and the factors
      associated with iron-folate consumption among post-natal mothers in Nepal. This
      study utilised the data of Nepal Demographic and Health Survey (NDHS) 2011. The
      NDHS 2011 is a cross sectional and nationally representative survey. Of the 4,148
      respondents, only 20.7% consumed iron throughout the post-natal period for 45
      days. Mothers who had higher and secondary education [adjusted Odd ratio (aOR)
      3.101; 95% CI (2.268-4.240)]; had attended four or more antenatal care visits
      [aOR 9.406; 95% CI (5.552-15.938)]; lived in Far-western development region [aOR
      1.822; 95% CI (1.387-2.395)]; delivered in health facility [aOR 1.335; 95% CI
      (1.057-1.687)]; and attended postnatal care [aOR 2.348; 95% CI (1.859-2.965)]
      were more likely to take iron for 45 days of postpartum. Intervention to increase
      the compliance with the postpartum iron-folate supplementation are required to
      avoid adverse pregnancy outcomes associated with poor iron status with especial
      focus on the mothers who delivered at homes and did not attend post-natal check
      up.

PMID- 24322601
TI  - Determining the storage, availability and reactivity of NH3 within Cu-Chabazite
      based Ammonia Selective Catalytic Reduction systems.
AB  - Three different types of NH3 species can be simultaneously present on Cu(2+)
      exchanged CHA-type zeolites, commonly used in Ammonia Selective Catalytic
      Reduction (NH3-SCR) systems. These include ammonium ions (NH4(+)), formed on the
      Bronsted acid sites, [Cu(NH3)4](2+) complexes, resulting from NH3 coordination
      with the Cu(2+) Lewis sites, and NH3 adsorbed on extra-framework Al (EFAl)
      species, in contrast to the only two reacting NH3 species recently reported on Cu
      SSZ-13 zeolite. The NH4(+) ions react very slowly in comparison to NH3
      coordinated to Cu(2+) ions and are likely to contribute little to the standard
      NH3-SCR process, with the Bronsted groups acting primarily as NH3 storage sites.
      The availability/reactivity of NH4(+) ions can be however, notably improved by
      submitting the zeolite to repeated exchanges with Cu(2+), accompanied by a
      remarkable enhancement in the low temperature activity. Moreover, the presence of
      EFAl species could also have a positive influence on the reaction rate of the
      available NH4(+) ions. These results have important implications for NH3 storage
      and availability in Cu-Chabazite-based NH3-SCR systems. 

PMID- 24322602
TI  - Highly efficient colorimetric detection of target cancer cells utilizing superior
      catalytic activity of graphene oxide-magnetic-platinum nanohybrids.
AB  - Enzyme-linked immunosorbent assays (ELISAs) have most widely been applied in
      immunoassays for several decades. However, several unavoidable limitations (e.g.,
      instability caused by structural unfolding) of natural enzymes have hindered
      their widespread applications. Here, we describe a new nanohybrid consisting of
      Fe3O4 magnetic nanoparticles (MNPs) and platinum nanoparticles (Pt NPs),
      simultaneously immobilized on the surface of graphene oxide (GO). By
      synergistically integrating highly catalytically active Pt NPs and MNPs on GO
      whose frameworks possess high substrate affinity, the nanohybrid is able to
      achieve up to a 30-fold higher maximal reaction velocity (V(max)) compared to
      that of free GO for the colorimetric reaction of the peroxidase substrate,
      3,3',5,5'-tetramethylbenzidine (TMB), and enable rapid detection of target cancer
      cells. Specifically, using this new assay system, clinically important breast
      cancer cells are detected in a 5 min time period at room temperature with high
      specificity and sensitivity. The remarkably high capability to catalyze oxidation
      reactions could allow the nanohybrid to replace conventional peroxidase-based
      immunoassay systems as part of new, rapid, robust and convenient assay systems
      which can be widely utilized for the identification of important target
      molecules.

PMID- 24322603
TI  - The fallopian canal: a comprehensive review and proposal of a new classification.
AB  - INTRODUCTION: The facial nerve follows a complex course through the skull base.
      Understanding its anatomy is crucial during standard skull base approaches and
      resection of certain skull base tumors closely related to the nerve, especially,
      tumors at the cerebellopontine angle. METHODS: Herein, we review the fallopian
      canal and its implications in surgical approaches to the skull base. Furthermore,
      we suggest a new classification. CONCLUSIONS: Based on the anatomy and
      literature, we propose that the meatal segment of the facial nerve be included as
      a component of the fallopian canal. A comprehensive knowledge of the course of
      the facial nerve is important to those who treat patients with pathology of or
      near this cranial nerve.

PMID- 24322604
TI  - Antimicrobial treatment options for neurosurgical ventricular shunt infections in
      children from 1993 to 2012: a systematic review.
AB  - PURPOSE: The aim of this systematic review was to review studies that existed
      from 1993 to 2012 regarding antimicrobial treatment options of paediatric
      neurosurgical shunt. METHODS: Studies were identified from MEDLINE, Scopus and
      Cochrane databases using a search strategy that was registered on the PROSPERO
      database. Studies were included if they had two or more patients, aged less than
      18 years, and also specified the organism and antimicrobial treatment that was
      used. RESULTS: The search yielded 2,985 articles, and 76 articles were suitable
      for full review. In the final qualitative analysis, only eight studies were
      included, involving 86 participants. The most common antimicrobial regimens for
      Gram-positive infections was intravenous and intrathecal vancomycin (n = 7),
      followed by intravenous vancomycin monotherapy. CONCLUSION: This systematic
      review has shown that there are no prospective randomised studies of
      antimicrobial treatment options for paediatric neurosurgical patients in the last
      20 years, and larger prospective studies are urgently required for this serious
      infection. There is some limited case series showing the benefits of certain
      antimicrobials such as vancomycin and ceftriaxone, but a larger case series or
      randomised controlled trial is required, particularly to establish the benefit,
      if any, of additional intraventricular antimicrobials.

PMID- 24322605
TI  - Prospective investigation of anterior pituitary function in the acute phase and
      12 months after pediatric traumatic brain injury.
AB  - PURPOSE: Although head trauma is common in childhood, there is no enough
      prospective study investigating both acute phase and 12 months after injury.
      Therefore, a prospective clinical trial was planned to evaluate the pituitary
      function in childhood in the acute and chronic phase after traumatic brain injury
      (TBI). METHODS: Forty-one children (27 boys and 14 girls, mean age 7 +/- 4.3),
      who were admitted to neurosurgery intensive care unit due to head trauma, were
      included. Twenty-one (51.2 %) patients had mild, 10 (24.4 %) had moderate, and 10
      (24.4 %) had severe TBI. Twenty-two of them were reevaluated 12 months after TBI.
      Basal pituitary hormone levels were measured during acute (first 24 h) and
      chronic phase of TBI. Additionally, in the chronic phase, GHRH-arginine test was
      used for the diagnosis of growth hormone (GH) deficiency. RESULTS: In the acute
      phase, 10 patients (24.4 %) had ACTH deficiency, and the overall 44.3 % of
      patients had at least one pituitary hormone dysfunction. All the pituitary
      hormone deficiencies during the acute phase were recovered after 12 months. Two
      patients (9.1 %) had new-onset GH deficiency in the chronic phase, and in one of
      them, ACTH deficiency was also present. CONCLUSIONS: Present prospective data
      clearly demonstrated that most of the hormonal changes in the early acute phase
      were transient, suggesting an adaptive response, and these changes did not
      predict the hormone deficiencies after 1 year. In the chronic phase, although GH
      deficiency was present, the frequency of TBI-induced hypopituitarism was clearly
      lower than the adult patients.

PMID- 24322606
TI  - Pediatric intracranial aneurysms--our experience and review of literature.
AB  - PURPOSE: Intracranial aneurysms in children are not as common as in adults and
      there are many differences in the etiology, demographic variables, aneurysm
      location, aneurysm morphological characteristics, clinical presentation, and
      outcome in pediatric and adult intracranial aneurysms. METHODS: All children
      (<=18 years) suffering from intracranial aneurysm managed at our center from July
      2001 through June 2013 were included in the study, and the details of these
      patients were retrieved from the computerized database of our hospital.
      OBSERVATIONS: A total of 62 pediatric patients were treated for 74 aneurysms
      during the study period and constituted 2.3% of all intracranial aneurysms
      treated during the same period. The mean age at presentation was 13.5 years.
      Headache (82%) was the commonest presenting feature; other symptoms included
      seizures (21%), ictal loss of consciousness (27%), and motor/cranial nerve
      deficits (22.6%). Computed tomogram revealed subarachnoid hemorrhage in 58% of
      patients. Eighty-two percent of aneurysms were in anterior circulation. Sixty
      seven percent of aneurysms were complex aneurysms. Fifty-eight percent of
      patients underwent surgical intervention while 30% underwent endovascular
      procedures. Twenty-one percent of the patients developed vasospasm. There was no
      postoperative mortality. Favorable outcome was seen in 72% of the patients.
      CONCLUSIONS: Pediatric intracranial aneurysms are uncommon as compared to in
      adult patients. Seizures and cranial nerve involvement are seen more often as the
      presenting features in children. Posterior circulation aneurysms are more common
      in children, as are the internal carotid artery bifurcation aneurysms. There is
      high incidence of giant, posttraumatic, and mycotic aneurysms in children.

PMID- 24322607
TI  - Inducible nitric oxide synthase inhibits oxygen consumption in collateral
      dependent myocardium.
AB  - Following coronary artery occlusion growth of collateral vessels can provide an
      effective blood supply to the dependent myocardium. The ischemia, which results
      in growth of collateral vessels, recruits an inflammatory response with
      expression of cytokines and growth factors, upregulation of endothelial nitric
      oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of
      inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes.
      Because NO is a potent collateral vessel dilator, this study examined whether NO
      derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in
      the collateral region. Nonselective NOS inhibition with N(G)-nitro-l-arginine
      (LNA) caused vasoconstriction with a significant decrease in MBF to the
      collateral region during exercise. In contrast, the highly selective iNOS
      inhibitor 1400W caused a 21 +/- 5% increase of MBF in the collateral region. This
      increase in MBF following selective iNOS blockade was proportionate to an
      increase in myocardial O2 consumption (MVo2). The results suggest that NO
      produced by iNOS inhibits MVo2 in the collateralized region, so that the increase
      in MBF following iNOS blockade was the result of metabolic vasodilation secondary
      to an increase in MVo2. Thus the coordinated expression of iNOS to restrain MVo2
      and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand
      relationship and protect the collateralized myocardium from ischemia. 

PMID- 24322608
TI  - Aerobic exercise training increases plasma Klotho levels and reduces arterial
      stiffness in postmenopausal women.
AB  - The Klotho gene is a suppressor of the aging phenomena, and the secretion as well
      as the circulation of Klotho proteins decrease with aging. Although habitual
      exercise has antiaging effects (e.g., a decrease in arterial stiffness), the
      relationship between Klotho and habitual exercise remains unclear. In the present
      study, we investigated the effect of habitual exercise on Klotho, with a
      particular focus on arterial stiffness. First, we examined the correlation
      between plasma Klotho concentration and arterial stiffness (carotid artery
      compliance and beta-stiffness index) or aerobic exercise capacity [oxygen uptake
      at ventilatory threshold (VT)] in 69 healthy, postmenopausal women (50-76 years
      old) by conducting a cross-sectional study. Second, we tested the effects of
      aerobic exercise training on plasma Klotho concentrations and arterial stiffness.
      A total of 19 healthy, postmenopausal women (50-76 years old) were divided into
      two groups: control group and exercise group. The exercise group completed 12 wk
      of moderate aerobic exercise training. In the cross-sectional study, plasma
      Klotho concentrations positively correlated with carotid artery compliance and VT
      and negatively correlated with the beta-stiffness index. In the interventional
      study, aerobic exercise training increased plasma Klotho concentrations and
      carotid artery compliance and decreased the beta-stiffness index. Moreover, the
      changes in plasma Klotho concentration and arterial stiffness were found to be
      correlated. These results suggest a possible role for secreted Klotho in the
      exercise-induced modulation of arterial stiffness. 

PMID- 24322610
TI  - Effects of activation pattern and active stress development on myocardial shear
      in a model with adaptive myofiber reorientation.
AB  - It has been hypothesized that myofiber orientation adapts to achieve a preferred
      mechanical loading state in the myocardial tissue. Earlier studies tested this
      hypothesis in a combined model of left ventricular (LV) mechanics and remodeling
      of myofiber orientation in response to fiber cross-fiber shear, assuming
      synchronous timing of activation and uniaxial active stress development.
      Differences between computed and measured patterns of circumferential-radial
      shear strain E(cr) were assumed to be caused by limitations in either the LV
      mechanics model or the myofiber reorientation model. Therefore, we extended the
      LV mechanics model with a physiological transmural and longitudinal gradient in
      activation pattern and with triaxial active stress development. We investigated
      the effects on myofiber reorientation, LV function, and deformation. The effect
      on the developed pattern of the transverse fiber angle alpha(t,0) and the effect
      on global pump function were minor. Triaxial active stress development decreased
      amplitudes of E(cr) towards values within the experimental range and resulted in
      a similar base-to-apex gradient during ejection in model computed and measured
      E(cr). The physiological pattern of mechanical activation resulted in better
      agreement between computed and measured strain in myofiber direction, especially
      during isovolumic contraction phase and first half of ejection. In addition,
      remodeling was favorable for LV pump and myofiber function. In conclusion, the
      outcome of the combined model of LV mechanics and remodeling of myofiber
      orientation is found to become more physiologic by extending the mechanics model
      with triaxial active stress development and physiological activation pattern.

PMID- 24322609
TI  - Thoracic and abdominal aortas stiffen through unique extracellular matrix changes
      in intrauterine growth restricted fetal sheep.
AB  - Intrauterine growth restriction (IUGR) is a fetal complication of pregnancy
      epidemiologically linked to cardiovascular disease in the newborn later in life.
      However, the mechanism is poorly understood with very little research on the
      vascular structure and function during development in healthy and IUGR neonates.
      Previously, we found vascular remodeling and increased stiffness in the carotid
      and umbilical arteries, but here we examine the remodeling and biomechanics in
      the larger vessels more proximal to the heart. To study this question, thoracic
      and abdominal aortas were collected from a sheep model of placental insufficiency
      IUGR (PI-IUGR) due to exposure to elevated ambient temperatures. Aortas from
      control (n = 12) and PI-IUGR fetuses (n = 10) were analyzed for functional
      biomechanics and structural remodeling. PI-IUGR aortas had a significant increase
      in stiffness (P < 0.05), increased collagen content (P < 0.05), and decreased
      sulfated glycosaminoglycan content (P < 0.05). Our derived constitutive model
      from experimental data related increased stiffness to reorganization changes of
      increased alignment angle of collagen fibers and increased elastin (P < 0.05) in
      the thoracic aorta and increased concentration of collagen fibers in the
      abdominal aorta toward the circumferential direction verified through use of
      histological techniques. This fetal vascular remodeling in PI-IUGR may set the
      stage for possible altered growth and development and help to explain the
      pathophysiology of adult cardiovascular disease in previously IUGR individuals. 

PMID- 24322611
TI  - Amelioration of salt-induced vascular dysfunction in mesenteric arteries of Dahl
      salt-sensitive rats by missense mutation of extracellular superoxide dismutase.
AB  - Superoxide dismutase (SOD) enzymes, including extracellular SOD (ecSOD), are
      important for scavenging superoxide radicals (O2(.-)) in the vasculature. This
      study investigated vascular control in rats [SS-Sod(3m1Mcwi) (ecSOD(E124D))] with
      a missense mutation that alters a single amino acid (E124D) of ecSOD that
      produces a malfunctioning protein in the salt-sensitive (Dahl SS) genetic
      background. We hypothesized that this mutation would exacerbate endothelial
      dysfunction due to elevated vascular O2(.-) levels in SS, even under normal salt
      (NS; 0.4% NaCl) conditions. Aortas of ecSOD(E124D) rats fed standard rodent chow
      showed enhanced sensitivity to phenylephrine and reduced relaxation to
      acetylcholine (ACh) vs. SS rats. Endothelium-dependent dilation to ACh was
      unaffected by the mutation in small mesenteric arteries of ecSOD(E124D) rats fed
      NS diet, and mesenteric arteries of ecSOD(E124D) rats were protected from
      endothelial dysfunction during short-term (3-5 days) high-salt (HS; 4% NaCl)
      diet. ACh-induced dilation of mesenteric arteries of ecSOD(E124D) rats and SS
      rats fed NS diet was inhibited by N(G)-nitro-l-arginine methyl ester and/or by
      H2O2 scavenging with polyethylene glycol-catalase at higher concentrations of
      ACh. Total SOD activity was significantly higher in ecSOD(E124D) rats vs. SS
      controls fed HS diet, most likely reflecting a compensatory response to loss of a
      functional ecSOD isoform. These findings indicate that, contrary to its effect in
      the aorta, this missense mutation of ecSOD in the SS rat genome has no negative
      effect on vascular function in small resistance arteries, but instead protects
      against salt-induced endothelial dysfunction, most likely via compensatory
      mechanisms involving an increase in total SOD activity. 

PMID- 24322612
TI  - A translational approach to probe the proarrhythmic potential of cardiac
      alternans: a reversible overture to arrhythmogenesis?
AB  - Electrocardiographic alternans, a phenomenon of beat-to-beat alternation in
      cardiac electrical waveforms, has been implicated in the pathogenesis of
      ventricular arrhythmias and sudden cardiac death (SCD). In the clinical setting,
      a positive microvolt T-wave alternans test has been associated with a heightened
      risk of arrhythmic mortality and SCD during medium- and long-term follow-up.
      However, rather than merely being associated with an increased risk for SCD,
      several lines of preclinical and clinical evidence suggest that cardiac alternans
      may play a causative role in generating the acute electrophysiological substrate
      necessary for the onset of ventricular arrhythmias. Deficiencies in Ca(2+)
      transport processes have been implicated in the genesis of alternans at the
      subcellular and cellular level and are hypothesized to contribute to the
      conditions necessary for dispersion of refractoriness, wave break, reentry, and
      onset of arrhythmia. As such, detecting acute surges in alternans may provide a
      mechanism for predicting the impending onset of arrhythmia and opens the door to
      delivering upstream antiarrhythmic therapies. In this review, we discuss the
      preclinical and clinical evidence to support a causative association between
      alternans and acute arrhythmogenesis and outline the potential clinical
      implications of such an association. 

PMID- 24322613
TI  - Cessation of contraction induces cardiomyocyte remodeling during zebrafish
      cardiogenesis.
AB  - Contraction regulates heart development via a complex mechanotransduction process
      controlled by various mechanical forces. Here, we exploit zebrafish embryos as an
      in vivo animal model to discern the contribution from different mechanical forces
      and identify the underlying mechanotransductive signaling pathways of
      cardiogenesis. We treated 2 days postfertilization zebrafish embryos with
      Blebbistatin, a myosin II inhibitor, to stop cardiac contraction, which induces a
      response termed cessation of contraction-induced cardiomyocyte (CM) enlargement
      (CCE). Accompanying the CCE, lateral fusion of myofibrils was attenuated within
      CMs. The CCE can be blunted by loss of blood in tail-docked zebrafish but not in
      cloche mutant fish, suggesting that transmural pressure rather than shear stress
      is accountable for the chamber enlargement. By screening a panel of small
      molecule inhibitors, our data suggested essential functions of phosphoinositide 3
      kinase signaling and protein synthesis in CCE, which are independent of the
      sarcomere integrity. In summary, we defined a unique CCE response in genetically
      tractable zebrafish embryos. A panel of assays was established to verify the
      contribution from extrinsic forces and interrogate underlying signaling pathways.

PMID- 24322614
TI  - Larger late sodium current density as well as greater sensitivities to ATX II and
      ranolazine in rabbit left atrial than left ventricular myocytes.
AB  - An increase of cardiac late sodium current (INa.L) is arrhythmogenic in atrial
      and ventricular tissues, but the densities of INa.L and thus the potential
      relative contributions of this current to sodium ion (Na(+)) influx and
      arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell
      and cell-attached patch-clamp techniques were used to measure INa.L in rabbit
      left atrial and ventricular myocytes under identical conditions. The density of
      INa.L was 67% greater in left atrial (0.50 +/- 0.09 pA/pF, n = 20) than in left
      ventricular cells (0.30 +/- 0.07 pA/pF, n = 27, P < 0.01) when elicited by step
      pulses from -120 to -20 mV at a rate of 0.2 Hz. Similar results were obtained
      using step pulses from -90 to -20 mV. Anemone toxin II (ATX II) increased INa.L
      with an EC50 value of 14 +/- 2 nM and a Hill slope of 1.4 +/- 0.1 (n = 9) in
      atrial myocytes and with an EC50 of 21 +/- 5 nM and a Hill slope of 1.2 +/- 0.1
      (n = 12) in ventricular myocytes. Na(+) channel open probability (but not mean
      open time) was greater in atrial than in ventricular cells in the absence and
      presence of ATX II. The INa.L inhibitor ranolazine (3, 6, and 9 MUM) reduced
      INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II.
      In summary, rabbit left atrial myocytes have a greater density of INa.L and
      higher sensitivities to ATX II and ranolazine than rabbit left ventricular
      myocytes. 

PMID- 24322615
TI  - Resveratrol treatment rescues neurovascular coupling in aged mice: role of
      improved cerebromicrovascular endothelial function and downregulation of NADPH
      oxidase.
AB  - Moment-to-moment adjustment of cerebral blood flow (CBF) to neuronal activity via
      neurovascular coupling is essential for the maintenance of normal neuronal
      function. Increased oxidative stress that occurs with aging was shown to impair
      neurovascular coupling, which likely contributes to a significant age-related
      decline in higher cortical function, increasing the risk for vascular cognitive
      impairment. Resveratrol is a polyphenolic compound that exerts significant
      antiaging protective effects in large vessels, but its effects on the
      cerebromicrovasculature remain poorly defined. The present study was undertaken
      to investigate the capacity of resveratrol to improve neurovascular coupling in
      aging. In aged (24-mo-old) C57BL/6 mice N(omega)-nitro-l-arginine methyl ester
      sensitive, nitric oxide-mediated CBF responses to whisker stimulation and to the
      endothelium-dependent dilator acethylcholine (ACh) were impaired compared with
      those in young (3-mo-old) mice. Treatment of aged mice with resveratrol rescued
      neurovascular coupling and ACh-induced responses, which was associated with
      downregulation of cortical expression of NADPH oxidase and decreased levels of
      biomarkers of oxidative/nitrative stress (3-nitrotyrosine, 8-isoprostanes).
      Resveratrol also attenuated age-related increases in reactive oxygen species
      (ROS) production in cultured cerebromicrovascular endothelial cells (DCF
      fluorescence, flow cytometry). In conclusion, treatment with resveratrol rescues
      cortical neurovascular coupling responses to increased neuronal activity in aged
      mice, likely by restoring cerebromicrovascular endothelial function via
      downregulation of NADPH oxidase-derived ROS production. Beneficial
      cerebromicrovascular effects of resveratrol may contribute to its protective
      effects on cognitive function in aging. 

PMID- 24322616
TI  - Sex differences in forearm vasoconstrictor response to voluntary apnea.
AB  - Clinical evidence indicates that obstructive sleep apnea is more common and more
      severe in men compared with women. Sex differences in the vasoconstrictor
      response to hypoxemia-induced sympathetic activation might contribute to this
      clinical observation. In the current laboratory study, we determined sex
      differences in the acute physiological responses to maximal voluntary end
      expiratory apnea (MVEEA) during wakefulness in healthy young men and women (26 +/
      1 yr) as well as healthy older men and women (64 +/- 2 yr). Mean arterial
      pressure (MAP), heart rate (HR), brachial artery blood flow velocity (BBFV,
      Doppler ultrasound), and cutaneous vascular conductance (CVC, laser Doppler
      flowmetry) were measured, and changes in physiological parameters from baseline
      were compared between groups. The breath-hold duration and oxygen-saturation
      nadir were similar between groups. In response to MVEEA, young women had
      significantly less forearm vasoconstriction compared with young men (DeltaBBFV: 2
      +/- 7 vs. -25 +/- 6% and DeltaCVC: -5 +/- 4 vs. -31 +/- 4%), whereas DeltaMAP (12
      +/- 2 vs. 16 +/- 3 mmHg) and DeltaHR (4 +/- 2 vs. 6 +/- 3 bpm) were comparable
      between groups. The attenuated forearm vasoconstriction in young women was not
      observed in postmenopausal women (DeltaBBFV -21 +/- 5%). We concluded that young
      women have blunted forearm vasoconstriction in response to MVEEA compared with
      young men, and this effect is not evident in older postmenopausal women. These
      data suggest that female sex hormones dampen neurogenic vasoconstriction in
      response to apnea-induced hypoxemia. 

PMID- 24322619
TI  - Randomly broken fragment PCR with 5' end-directed adaptor for genome walking.
AB  - Many genome walking methods based on polymerase chain reaction (PCR) are
      available, including those with and without restriction enzyme modification.
      Nevertheless, these methods suffer from low reproducibility, inefficiency, and
      non-specificity. Here, we present a traceable and efficient PCR strategy:
      randomly broken fragment PCR with 5' end-directed adaptor for genome walking. The
      genome is first fragmented randomly. After blunting ends, the fragments are
      ligated to the 5' end-directed adaptors. Semi-nested PCR is then performed. Thus,
      we can obtain an unknown sequence by cloning the fragments of interest, followed
      by sequencing. This method effectively bypasses the above-mentioned obstacles and
      offers the advances: 1) genome fragmentation without using restriction enzymes;
      2) enhancement of primer specificity and the prevention of self-ligation between
      the adaptors by employing a 5' end-directed adaptor. All of the steps in this new
      method are straightforward, and the unknown sequence can be definitively obtained
      by merely applying the method once. 

PMID- 24322620
TI  - Models of hepatotoxicity and the underlying cellular, biochemical and
      immunological mechanism(s): a critical discussion.
AB  - Liver is a primary organ involved in biotransformation of food and drugs. Hepatic
      diseases are a major worldwide problem. Hepatic disorders are mainly caused by
      toxic chemicals (alcohol), xenobiotics (carbon tetrachloride, chlorinated
      hydrocarbons and gases CO2 and O2) anticancer (azathioprine, doxorubicin,
      cisplatin), immunosuppressant (cyclosporine), analgesic anti-inflammatory
      (paracetamol, thioacetamide), anti-tubercular (isoniazid, rifampicin) drugs,
      biologicals (Bacillus-Calmette-Guerin vaccine), radiations (gamma radiations),
      heavy metals (cadmium, arsenic), mycotoxin (aflatoxin), galactosamine,
      lipopolysaccharides, etc. Various risk factors for hepatic injury include
      concomitant hepatic diseases, age, gender, alcoholism, nutrition and genetic
      polymorphisms of cytochrome P450 enzymes have also been emphasized. The present
      review enumerates various in vivo animal models and in vitro methods of hepatic
      injury using diverse toxicants, their probable metabolic pathways, and numerous
      biochemical changes viz. serum biomarkers enzymes, liver function, oxidative
      stress associated events like free radicals formation, lipid peroxidation, enzyme
      antioxidants and participation of cytokines (tumour necrosis factor-alpha,
      transforming growth factor-beta, tumour necrosis factor-related apoptosis
      inducing ligand), and other biomolecules (Fas and C-jun N-terminal kinase) are
      also discussed. The underlying cellular, molecular, immunological, and
      biochemical mechanism(s) of action responsible for liver damage (toxicity) are
      also been discussed. This review should be immensely useful for researchers
      especially for phytochemists, pharmacologists and toxicologists working on
      hepatotoxicity, hepatotoxic chemicals and drugs, hepatoprotective agents and drug
      research organizations involved especially in phytopharmaceuticals and other
      natural products.

PMID- 24322617
TI  - Novel role of transient receptor potential vanilloid 2 in the regulation of
      cardiac performance.
AB  - Transient receptor potential cation channels have been implicated in the
      regulation of cardiovascular function, but only recently has our laboratory
      described the vanilloid-2 subtype (TRPV2) in the cardiomyocyte, though its exact
      mechanism of action has not yet been established. This study tests the hypothesis
      that TRPV2 plays an important role in regulating myocyte contractility under
      physiological conditions. Therefore, we measured cardiac and vascular function in
      wild-type and TRPV2(-/-) mice in vitro and in vivo and found that TRPV2 deletion
      resulted in a decrease in basal systolic and diastolic function without affecting
      loading conditions or vascular tone. TRPV2 stimulation with probenecid, a
      relatively selective TRPV2 agonist, caused an increase in both inotropy and
      lusitropy in wild-type mice that was blunted in TRPV2(-/-) mice. We examined the
      mechanism of TRPV2 inotropy/lusitropy in isolated myocytes and found that it
      modulates Ca(2+) transients and sarcoplasmic reticulum Ca(2+) loading. We show
      that the activity of this channel is necessary for normal cardiac function and
      that there is increased contractility in response to agonism of TRPV2 with
      probenecid. 

PMID- 24322621
TI  - Ecotoxicological effects of a veterinary food additive, copper sulphate, on
      antioxidant enzymes and mRNA expression in earthworms.
AB  - The present study was aimed to investigate the effect of the veterinary food
      additive copper sulphate (CuSO4) on the eco-toxicological responses of earthworms
      Eisenia fetida (E. fetida). The following biomarkers were measured: catalase
      (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione
      S-transferase (GST) activities. Gene expression analyses such as metallothionein
      (MT) and heat shock protein 70 (Hsp70) were also examined. A time-dependent
      increase of CAT activity was found at 400 mg/kg and SOD activity at 200 and 400
      mg/kg. The highest expression of Hsp70 (4.4-fold) was observed at day 15 at 400
      mg/kg. Our results indicated that the measured antioxidant enzymes (except GST)
      had the ability to provide antioxidant defenses against the stressor; and
      compared to expression of MT, expression of Hsp70 could be more reliable
      molecular tools with predictive possibilities to monitor the eco-toxicity of
      stressors such as feed additive CuSO4.

PMID- 24322622
TI  - Evaluation of deoxynivalenol-induced toxic effects on DF-1 cells in vitro: cell
      cycle arrest, oxidative stress, and apoptosis.
AB  - Deoxynivalenol (DON) is one of the most common mycotoxin contaminants of raw and
      processed cereal food. Lymphoid cells and fibroblasts are specified to be the
      most DON-sensitive cell types. In this study, we investigated the toxic effects
      of DON in chicken embryo fibroblast DF-1 cells. The results showed that DON
      significantly inhibited DF-1 cell viability in both a time- and concentration
      dependent manner. DON could also inhibit the proliferation of DF-1 cells through
      G2/M phase arrest in the cell cycle progression. Moreover, oxidative stress
      induced by DON was indicated by increased levels of reactive oxygen species
      (ROS), malondialdehyde (MDA), and decreased levels of glutathione (GSH) and
      superoxide dismutase (SOD). In addition, DON could also cause mitochondrial
      damage by decreasing the mitochondrial membrane potential and induce apoptosis
      accompanied with the up-regulation of apoptosis-related genes including Caspase
      3, Caspase-8, Caspase-9, and AIFM1. These results suggested that DON could cause
      cell cycle arrest, oxidative stress, and apoptosis in DF-1 cells. 

PMID- 24322623
TI  - Dose responsive effects of cisplatin in L02 cells using NMR-based metabolomics.
AB  - Cisplatin is an effective chemotherapeutic agent for the treatment of various
      cancers, such as bladder cancer, epithelial ovarian cancer, cervical cancer, and
      so on. However, cisplatin can cause various side effects. In this study, the dose
      responsive effects of cisplatin were investigated in an in vitro model of human
      liver cells (L02) using NMR-based metabolomics. The inverted U-shaped curve of
      cell proliferation confirmed the hormetic effects of cisplatin (from 1 nM to 1
      mM) in L02 cells. However, the metabolite changes revealed both U-shaped
      (ethanol, lactate, aspartate, choline, etc.) and inverted U-shaped (glutamate,
      glutamine, 4-aminobutyrate, myo-inositol, etc.) curves induced by three typical
      concentrations of cisplatin which covered the inverted U-shaped curve as
      indicated by the cell proliferation assay. These findings suggested that a
      macroscopic hormesis phenomenon on the cell proliferation could be reflected by
      both stimulated and inhibited metabolites and corresponding metabolic pathways to
      cisplatin treatments. Therefore, a global analysis using metabolomics may give a
      broader view into the dose-response relationship than using a single endpoint at
      molecular levels.

PMID- 24322624
TI  - Annular erythema associated with Sjogren's syndrome preceding overlap syndrome of
      rheumatoid arthritis and polymyositis with anti-PL-12 autoantibodies.

PMID- 24322625
TI  - Peroxynitrite chemistry derived from nitric oxide reaction with a Cu(II)-OOH
      species and a copper mediated NO reductive coupling reaction.
AB  - New peroxynitrite-copper chemistry ensues via addition of nitric oxide (NO(g)) to
      a Cu(II)-hydroperoxo species. In characterizing the system, the ligand-Cu(i)
      complex was shown to effect a seldom observed NO(g) reductive coupling reaction.
      Biological implications are discussed. 

PMID- 24322626
TI  - Assessing potential glycemic overtreatment in persons at hypoglycemic risk.
AB  - IMPORTANCE: Although serious hypoglycemia is a common adverse drug event in
      ambulatory care, current performance measures do not assess potential
      overtreatment. OBJECTIVE: To identify high-risk patients who had evidence of
      intensive glycemic management and thus were at risk for serious hypoglycemia.
      DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients in the
      Veterans Health Administration receiving insulin and/or sulfonylureas in 2009.
      MAIN OUTCOMES AND MEASURES: Intensive control was defined as the last hemoglobin
      A1c (HbA1c) measured in 2009 that was less than 6.0%, less than 6.5%, or less
      than 7.0%. The primary outcome measure was an HbA1c less than 7.0% in patients
      who were aged 75 years or older who had a serum creatinine value greater than 2.0
      mg/dL or had a diagnosis of cognitive impairment or dementia. We also assessed
      the rates in patients with other significant medical, neurologic, or mental
      comorbid illness. Variation in rates of possible glycemic overtreatment was
      evaluated among 139 Veterans Health Administration facilities grouped within 21
      Veteran Integrated Service Networks. RESULTS: There were 652,378 patients who
      received insulin and/or a sulfonylurea with an HbA1c test result. Fifty percent
      received sulfonylurea therapy without insulin; the remainder received insulin
      therapy. We identified 205,857 patients (31.5%) as the denominator for the
      primary outcome measure; 11.3% had a last HbA1c value less than 6.0%, 28.6% less
      than 6.5%, and 50.0% less than 7.0%. Variation in rates by Veterans Integrated
      Service Network facility ranged 8.5% to 14.3%, 24.7% to 32.7%, and 46.2% to 53.4%
      for HbA1c less than 6.0%, less than 6.5%, and less than 7.0%, respectively. The
      magnitude of variation by facility was larger, with overtreatment rates ranging
      from 6.1% to 23.0%, 20.4% to 45.9%, and 39.7% to 65.0% for HbA1c less than 6.0%,
      less than 6.5%, and less than 7.0%, respectively. The maximum rate was nearly 4
      fold compared with the minimum rates for HbA1c less than 6.0%, followed by 2.25
      fold for HbA1c less than 6.5% and less than 2-fold for HbA1c less than 7.0%. When
      comorbid conditions were included, 430,178 patients (65.9%) were identified as
      high risk. Rates of overtreatment were 10.1% for HbA1c less than 6.0%, 25.2% for
      less than 6.5%, and 44.3% for less than 7.0%. CONCLUSIONS AND RELEVANCE: Patients
      with risk factors for serious hypoglycemia represent a large subset of
      individuals receiving hypoglycemic agents; approximately one-half had evidence of
      intensive treatment. A patient safety indicator derived from administrative data
      can identify high-risk patients for whom reevaluation of glycemic management may
      be appropriate, consistent with meaningful use criteria for electronic medical
      records.

PMID- 24322627
TI  - Femoral head asymmetry and coxa magna: anatomic study.
AB  - BACKGROUND: Coxa magna, the asymmetrical circumferential enlargement of the
      femoral head, is an important sequela of pediatric disorders such as Legg-Calve
      Perthes disease. Definitions vary because of lack of controls and a scarcity of
      research on the distribution of the femoral head asymmetry. This study aims at
      defining the normal distribution of asymmetry between the left and the right
      femoral head and neck in the population and how demographics affect these
      properties. The study also looked at the distribution of side dominance (left or
      right). METHODS: This study measured 230 paired femurs from individuals (20 to 40
      y old) distributed for sex and ethnicity. The height and weight of the
      individuals were also recorded. The femoral head diameter and minimal femoral
      neck diameter in the anteroposterior view were measured on each paired femurs.
      The absolute and percent differences were determined to define asymmetry.
      RESULTS: Most of the population fell within 3% of asymmetry for the femoral head
      and 4% for the femoral neck. The maximum head percent asymmetry was 7.4%.
      Absolute difference in millimeters to percent asymmetry showed a ratio of 2:1 for
      the femoral head and 3:1 for the femoral neck. African Americans showed greater
      femoral head symmetry and a bias toward left-sided femoral head and neck
      enlargement when compared with their white counterparts. CONCLUSIONS: There was a
      high degree of symmetry between the left and right femoral heads and necks, which
      supports definitions found in the literature that define coxa magna above 10%.
      This study defines asymmetry in the femoral head in the normal population, which
      will help to define a quantitative definition of coxa magna.

PMID- 24322628
TI  - Efficacy of reduction maneuvers for "pulled elbow" in children: a prospective
      study of 115 cases.
AB  - BACKGROUND: The objective of our study is to determine the relative efficacy of
      the 2 reduction maneuvers, hyperpronation (HP) and supination-flexion (SF), in
      pulled elbow (PE). METHODS: We conducted a randomized, prospective study of 2
      reduction maneuvers in 115 patients with PE and a mean age of 2 years and 3
      months. Patients were randomly divided into 2 groups: group A, with 65 children
      (56.52%) who underwent HP; and group B, with 50 children (43.47%) who underwent
      SF. RESULTS: In 97.39% of the children, reduction was achieved by manipulation.
      Reduction was achieved at first attempt (using either maneuver) in 101 of 115
      patients (87.82%), with 93.84% success for HP and 80% for SF (P=0.0243). Most
      patients in whom our first attempts failed (85.71%) had undergone prior
      manipulation: 100% of treatment failures from group A; and 80% of failures from
      group B. Most (95.04%) patients in whom our first attempts succeeded had not
      undergone prior manipulation: 93.44% from group A; and 97.5% from group B. A
      significant relationship was found when comparing those who had undergone prior
      manipulation from group A (P=0.0001) and group B (P=0.000000072). CONCLUSIONS:
      Although both SF and HP are effective for reduction of PE, a higher first-attempt
      success rate was achieved by HP, and this should therefore be the first maneuver
      used. In recurring cases, it would seem appropriate to teach the child's parents
      the HP maneuver as the most effective and easiest to do.

PMID- 24322629
TI  - Segmental metadiaphyseal humeral bone loss in pediatric trauma patients: a case
      series.
AB  - BACKGROUND: The management of posttraumatic bone loss is complicated and often
      requires complex reconstructive procedures. No options exist that are specific to
      the treatment of the growing skeleton that has intercalary bone loss. We have
      observed reconstitution of the humerus in 2 cases that have precluded extensive
      management. METHODS: Two pediatric patients sustained traumatic injuries to the
      upper extremities, including humeral bone loss, and are presented after
      spontaneous reconstitution of the segmental bone loss. RESULTS: With treatment
      restricted to soft-tissue injury and bone stabilization with external fixation,
      both patients demonstrated radiographic healing of humeral segmental bone loss.
      Both patients were thought to have a partially intact periosteal sleeve. They
      have returned to sporting activities with mild loss of function. CONCLUSIONS: In
      certain pediatric injuries, spontaneous healing of segmental bone defects can
      occur. This response may obviate the need for complex, interventional procedures.
      LEVELS OF EVIDENCE: Level IV-case series.

PMID- 24322630
TI  - Percutaneous trigger thumb release in children: neither effective nor safe.
AB  - BACKGROUND: Although percutaneous trigger thumb release has been extensively used
      in adults, the technique is not widespread in children. The purpose of this study
      was to evaluate the efficacy and safety of percutaneous trigger thumb release in
      the pediatric age group. METHODS: Twenty consecutive thumbs of 15 patients
      scheduled for surgical release of the A1 pulley were included in this cohort.
      Each patient received first the percutaneous release (PR) followed by an open
      release (OR) and served as self-controls. Thumb extension was assessed
      immediately before PR, after PR, and finally after OR, using a goniometer. Extent
      of the A1 pulley release, iatrogenic injury to the digital nerve and vessels, and
      flexor tendon laceration was assessed after PR. The distance between the PR and
      the digital nerve was measured in millimeters. Comparison between thumb extension
      after PR and OR was made using a paired t test. RESULTS: Preoperative range of
      motion averaged -45.2 +/- 21.7 degrees loss of extension (range, -80 to -10
      degrees), decreased to -4 +/- 8 degrees loss of extension (range, -25 to 0
      degrees) after PR, and to 0 degrees after OR. Clinically, release was complete in
      14 cases (70%) and partial in 6 cases (30%). Once the thumb was approached, we
      confirmed that A1 pulley was completely cut in 4 cases (20%), to >75% in 2 cases
      (10%), and between 50% and 75% in the remaining 14 cases (70%). There were no
      neurovascular iatrogenic injuries. Mean distance between the needle and the
      digital nerve was 2.45 +/- 0.9 mm (range, 1 to 4 mm). Lacerations to the flexor
      tendons were observed in 80% of the cases. CONCLUSIONS: We do not recommend PR in
      the pediatric thumb given the risk of neurovascular iatrogenic injury or
      incomplete A1 pulley release. LEVEL OF EVIDENCE: Level II therapeutic study
      prospective comparative study.

PMID- 24322631
TI  - Kinematic evaluation of 4 pediatric collars and distribution of cervical movement
      between primary and coupled angles.
AB  - BACKGROUND: Primary and coupled angle restrictions, when neck collars are used,
      have been investigated mainly in adults and not yet in children. PURPOSE: To
      evaluate the efficiency of 4 pediatric collars in reducing cervical range of
      motion (ROM) in primary and coupled planes. METHODS: Thirty asymptomatic children
      (16 boys and 14 girls) aged 6 to 12 years participated in the study. A motion
      analysis system was used to evaluate the ROM of the cervical spine during
      flexion/extension, left and right lateral bending, and left and right axial
      rotation. Primary and coupled ROM were evaluated in unbraced and braced
      conditions. Four cervical collars were tested: Philadelphia, Miami Jr, Necloc,
      and the conventional Hard Collar. Thirteen subjects were tested 2 times to
      evaluate the repeatability of the parameters. The ROM in each plane was
      normalized to the sum of the ROM in the 3 planes, for each movement, to estimate
      the percentage of the movement in each plane (normalized ROM), in braced and
      unbraced conditions. The analysis of variance and post hoc Benferroni tests were
      applied on raw and normalized ROM. RESULTS: ROM collected in collars showed a
      significant difference compared with the unbraced condition. ROM obtained in
      Necloc and Miami Jr showed a significant difference compared with Philadelphia
      and conventional Hard Collar. The primary plane is activated at 80% during
      flexion-extension and left-right axial rotation; however, 55% of the total
      movement was completed in the frontal plane during left-right lateral bending in
      unbraced condition. Statistical differences in the normalized ROM were found
      between the braced and unbraced conditions and among collars. CONCLUSIONS: Necloc
      and Miami Jr presented the highest limitation of movement in the primary and
      secondary planes. The distribution strategy of a movement, between primary and
      coupled angles, is different between the braced and unbraced conditions.

PMID- 24322632
TI  - Dynamic Indocyanine Green (ICG) lymphography for breast cancer-related arm
      lymphedema.
AB  - BACKGROUND: Lymph transportation capacity is a critical function maintaining
      fluid circulation. After breast cancer treatments, lymph obstruction at the
      axilla leads to abnormal lymph circulation, resulting in lymph pump dysfunction.
      As well as lymph circulation, lymph pump function is important for lymphedema
      evaluation. METHODS: We assessed and analyzed lymph transportation capacity of 15
      breast cancer-related arm lymphedema patients using dynamic indocyanine green
      (ICG) lymphography. RESULTS: ICG velocity and transit time could evaluate lymph
      pump function; ICG velocity decreases and transit time increases as the
      lymphedema severity stage progresses. Measurement of ICG velocity required 3
      minutes after the dye injection, whereas that of transit time took more than 1
      hour in severe cases. CONCLUSIONS: ICG velocity can be easily obtained and is
      recommended for evaluation of lymph pump function. Dynamic ICG lymphography,
      which evaluates both lymph pump function and circulation, plays an important role
      in comprehensive assessment of lymphedema pathophysiology.

PMID- 24322633
TI  - Ischial pressure ulcers: long-term outcome of 2 surgical techniques.
AB  - BACKGROUND: The aim of our study was to analyze which of these 2 techniques
      (biceps femoris myocutaneous flap vs gluteus maximus myocutaneous flap) gave the
      best result for ischial pressure ulcers treatment. METHODS: A retrospective
      comparative analysis of medical records for stage III and IV pressure ulcers was
      conducted between the 2 groups by Fisher exact test for categorical variables
      (significance level P <0.05) followed by a survival analysis by the Kaplan-Meier
      method. RESULTS: Twenty-five patients were treated with biceps femoris flap
      against 8 patients with gluteus maximus flap, primary healing was obtained
      without complications in 32% of cases in biceps femoris group versus 62.5% in
      gluteus maximus group. No surgical techniques were statistically correlated with
      a lower recurrence (32% vs 0%, P = 0.152). CONCLUSIONS: We had no significant
      difference in recurrence rate between the 2 flaps. However, we had less morbidity
      in gluteus maximus flap group; indeed, we had zero rate of reoperation and a zero
      rate of recurrence. For that reason, we think that gluteus maximus flap seems to
      be the best technical coverage of ischial pressure ulcers.

PMID- 24322634
TI  - Fibronectin and craniofacial surgery.
AB  - Fibronectin is an essential component of the extracellular matrix. The role of
      fibronectin in craniofacial surgery has not been previously reviewed. Fibronectin
      mediates bone differentiation and development of the skull. Studies have shown
      that normal development of the skull requires a specific pattern of expression
      around the epithelial-mesenchymal interface of the neurocranium. Fibronectin is
      also essential in mediating the migration of neural crest cells to form the
      facial skeleton. The calvaria of patients with Apert and Crouzon syndromes have
      an abnormally elevated collagen level. However, fibronectin levels are elevated
      in the former syndrome and decreased in the latter syndrome. The significance of
      this requires further research. Fibronectin gene expression is increased in port
      wine-derived fibroblasts in patients with Sturge-Weber syndrome. Normal
      palatogenesis also requires a specific pattern of expression of fibronectin
      around the maxillary process as well as the roof of the stomodeum, and several
      studies have linked the development of cleft lip/palate to an imbalance of
      fibronectin content of the extracellular matrix. Fibronectin mediates cell-to
      cell attachment during repair of calvarial defects; hence, fibronectin has been
      used as a carrier for bone morphogenetic proteins to treat calvarial defects.
      Finally, fibronectin is now an essential component in stem cell technology
      related to craniofacial surgery. 

PMID- 24322635
TI  - Treatment of paraffin-induced lipogranuloma of the penis by bipedicled scrotal
      flap with Y-V incision.
AB  - OBJECTIVES: The authors aimed to report 5 cases of patients with penile
      lipogranuloma-induced full necrosis of penile skin, wherein they obtained good
      results from simultaneous implementation of Y-V incision to prevent the
      shortening of penile length together with bipedicular scrotal flap. METHODS: The
      full excision of penile lipogranuloma and a bipedicled scrotal flap was
      performed. After finishing the scrotal flap, for extension in length, the authors
      performed the inverted V incision on the upper skin of followed by partial
      resection of suspensory ligament and sutured up to subcutaneous tissue in the
      inverted Y shape, extending the dorsal portion skin toward the penis. RESULTS:
      There was no shortening in length of the penis or reduction in girth and the
      resulting penis had no difference to normal skin of penis, with almost no
      contraction of the scrotum, and all patients were satisfied with the visual
      postoperative shape of the penis. CONCLUSIONS: The authors had performed a
      complete excision of paraffinoma in patients with penile paraffinoma with
      concurrent skin necrosis and obtained good outcomes of preventing the shortening
      of penile length by performing a bipedicled scrotal flap with Y-V incision using
      the scrotal skin.

PMID- 24322636
TI  - Greater occipital nerve excision for occipital neuralgia refractory to nerve
      decompression.
AB  - BACKGROUND: Patients who undergo occipital nerve decompression for treatment of
      migraine headaches due to occipital neuralgia have already exhausted medical
      options for treatment. When surgical decompression fails, it is unknown how best
      to help these patients. We examine our experience performing greater occipital
      nerve (GON) excision for pain relief in this select, refractory group of
      patients. METHODS: A retrospective chart review supplemented by a follow-up
      survey was performed on all patients under the care of the senior author who had
      undergone GON excision after failing occipital nerve decompression. Headache
      severity was measured by the migraine headache index (MHI) and disability by the
      migraine disability assessment. Success rate was considered the percentage of
      patients who experienced a 50% or greater reduction in MHI at final follow-up.
      RESULTS: Seventy-one of 108 patients responded to the follow-up survey and were
      included in the study. Average follow-up was 33 months. The success rate of
      surgery was 70.4%; 41% of patients showed a 90% or greater decrease in MHI. The
      MHI changed, on average, from 146 to 49, for an average reduction of 63% (P <
      0.001). Migraine disability assessment scores decreased by an average of 49% (P <
      0.001). Multivariate analysis revealed that a diagnosis of cervicogenic headache
      was associated with failure of surgery. The most common adverse effect was
      bothersome numbness or hypersensitivity in the denervated area, occurring in up
      to 31% of patients. CONCLUSIONS: Excision of the GON is a valid option for pain
      relief in patients with occipital headaches refractory to both medical treatment
      and surgical decompression. Potential risks include failure in patients with
      cervicogenic headache and hypersensitivity of the denervated area. To provide the
      best outcome to these patients who have failed all previous medical and surgical
      treatments, a multidisciplinary team approach remains critical.

PMID- 24322638
TI  - Revision decompression and collagen nerve wrap for recurrent and persistent
      compression neuropathies of the upper extremity.
AB  - BACKGROUND: Recurrent or persistent compression neuropathies of the upper
      extremity, including carpal and cubital tunnel syndrome, present a difficult
      treatment challenge to the hand or peripheral nerve surgeon. Collagen conduits
      have been used successfully for decades in nerve injury repair, but have not been
      studied in the treatment of compression neuropathy. METHODS: Patients with
      recurrent or persistent compression neuropathies treated with a repeat
      decompression and collagen wrap from a 5-year period were retrieved from the
      Computerized Patient Record System database and 15 patient records were
      identified. A systematic review was performed for all articles from 1946 to 2012
      on secondary carpal and cubital tunnel syndrome. RESULTS: The mean age of the 15
      patients treated was 63.3 years and ranged from 35 to 86 years. The patients with
      revision carpal tunnel decompression had an 89% subjective response rate, whereas
      those with revision cubital tunnel decompression had an 83% resolution or
      improvement of symptoms. Visual analog scale decreased from a preoperative mean
      2.47 to 0.47 postoperatively and the mean number of opiate medications decreased
      from 0.67 to 0.40. We identified 32 papers using various treatment strategies for
      recurrent carpal tunnel syndrome with success rates ranging from 53% to 100%. We
      identified 18 papers on recurrent cubital tunnel syndrome, with success rates
      ranging from 33% to 100%, with a weighted success of 78.1% overall but 71.7% in
      the submuscular transposition group. CONCLUSIONS: Here we report on the novel
      technique of using a collagen matrix wrap in recurrent compression neuropathies
      with good success. The collagen wrap allows nerve gliding, protection from
      perineural scar formation, and a favorable microenvironment. Submuscular
      transposition seems to be no better than other methods of decompression for
      recurrent cubital tunnel syndrome in contrary to traditional teaching.

PMID- 24322639
TI  - End-to-end versus end-to-side motor and sensory neurorrhaphy in the repair of the
      acute muscle denervation.

PMID- 24322640
TI  - Autologous reconstruction of a complex form of Poland syndrome using 2 abdominal
      perforator free flaps.
AB  - Poland syndrome is the most frequent cause of congenital breast aplasia and
      hypoplasia. Breast and possible chest wall deformities can be treated with
      several surgical techniques, including implants, and pedicled or free flaps.We
      describe the case of a young patient with severe Poland syndrome with amastia,
      athelia, and deformity of the chest wall, and aplasia of 2 ribs. Marked
      hypoplasia of the ipsilateral latissimus dorsi muscle ruled out a reliable
      reconstructive option.Two perforator flaps were performed in a single-stage
      operation. A hemi-deep inferior epigastric perforator flap was harvested to
      correct the chest deformity, whereas the contralateral superficial inferior
      epigastric artery flap allowed breast reconstruction.No complications occurred
      and a subjectively and objectively pleasing cosmetic result was maintained at 3
      year follow-up. 

PMID- 24322641
TI  - Effect of side-stream smoking on random-pattern skin flap survival in rats.
AB  - The secondhand exposure to cigarette smoke is being considered evil, and damage
      caused by this passive exposure has been proven by several studies. To
      investigate the effects of sidestream smoke exposure on random-pattern skin flap
      survival, 20 female rats were separated into 2 groups: group A (n = 10) was
      exposed 6 weeks to the smoke from the burning cigarette (passive smoking) and
      group B (n = 10) was the control group. After 6 weeks of exposition, a dorsal
      McFarlane flap of 4 * 10 cm was performed in all rats. Two weeks after this
      procedure, the ratio of necrotic and total areas was calculated using computer
      programs. The median area of necrosis in group A was 29.5%, significantly higher
      than that in group B with 17.5% (P < 0.024). In conclusion, this study suggests
      increased risk of random-pattern skin flap necrosis after sidestream exposure to
      cigarette smoke. 

PMID- 24322642
TI  - Clinical application of cultured epithelial autografts on acellular dermal
      matrices in the treatment of extended burn injuries.
AB  - Achieving permanent replacement of skin in extensive full-thickness and deep
      partial-thickness burn injuries and chronic wounds remains one of the fundamental
      surgical problems. Presently, split-thickness skin grafts are still considered
      the best material for surgical repair of an excised burn wound. However, in burns
      that affect greater than 50% of total body surface area, the patient has
      insufficient areas of unaffected skin from which split-thickness skin grafts can
      be harvested. The use of cultured epithelial (or epidermal) autografts (CEAs) has
      achieved satisfactory results. But the take rate of CEAs is poor in full
      thickness bed or in chronically infected area. Providing temporary cover with
      allograft skin, or a more permanent allodermis, may increase clinical take. This
      review aims to (1) describe the use of CEAs in the regeneration of the epidermis,
      (2) introduce the application of the acellular dermal matrices (ADMs) in the
      clinics, and (3) enhance understanding of the CEAs applied with ADM as an
      appropriate strategy to treat the extended burn injuries. The current evidence
      regarding the cultured epithelial cell or keratinocyte autograft and dermal
      grafts applied in the treatment of burn injuries was investigated with an
      extensive electronic and manual search (MEDLINE and EMBASE). The included
      literature (N=136 publications) was critically evaluated focusing on the efficacy
      and safety of this technique in improving the healing of the deep dermal and full
      thickness burn injuries. This review concluded that the use of ADM with CEAs is
      becoming increasingly routine, particularly as a life-saving tool after acute
      thermal trauma.

PMID- 24322643
TI  - Wide local en bloc excision of subungual melanoma in situ.
AB  - Subungual melanoma is a rare but lethal form of melanoma. Amputation at the level
      of the interphalangeal joint or proximal has been described as appropriate
      surgical management for all stages of subungal melanoma. In cases of subungual
      melanoma in situ (SMIS), wide local excision can improve functional and aesthetic
      outcomes. We reviewed our experience of wide local excision for the treatment of
      SMIS. Between 2003 and 2010, we treated 9 cases of SMIS. We performed a
      retrospective review of this series looking at the primary outcomes of recurrence
      or metastasis. Average age was 40 years (range, 5-65 years). Presenting lesions
      were on the thumb (5) and index finger (4). All patients underwent definitive
      reconstruction with a combination of full-thickness skin graft (8) and
      paronychial advancement flap (6). Reexcision was performed when disease-free
      margins could not be confirmed. To date, there have been no cases of metastasis
      or local recurrence in any of our 9 patients (mean follow-up time of more than 4
      years). Wide local excision can improve functional and aesthetic outcomes with
      similar success in rates of local recurrence and metastasis when compared to
      treatment by amputation in SMIS. 

PMID- 24322644
TI  - The double unilimb z-plasty technique for whistler deformity repair in unilateral
      cleft lip patients: an anthropometric study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the symmetry in lip and
      vermillion height after using the double unilimb Z-plasty method for whistler
      deformity repair. DESIGN: This is a retrospective audit of 1 surgeon's outcome of
      52 consecutive performed whistler deformity repairs. SETTING: Data from the
      Outreach Surgical Center Program, Lima, Peru, were used. PATIENTS: Since 2009, 52
      adult patients with lip deformity related to unsatisfactory unilateral cleft lip
      repair were operated on using the double unilimb Z-plasty. All these patients met
      the study criterion of having anthropometric measurements performed at least 1
      year postoperatively. MAIN OUTCOME MEASURES: Data collection of lip and vermilion
      height was performed at the right and left side of the lip, immediately before
      the surgery (preoperatory) and at least 1 year postoperatively. The lip
      measurements were obtained using calipers. ANALYSIS: The matched pair t test
      analyses were performed when the assumptions required were met. When the
      normality assumption was not met, the Wilcoxon signed rank test, a nonparametric
      test, was used to assess the statistical significance of differences between the
      cleft side and the noncleft side. RESULTS: The study found no statistically
      significant differences between the right and left side in lip height (P = 0.51)
      and vermilion height (P = 0.57) after lip repair using the double unilimb Z
      plasty technique measured at least 1 year postoperatively. CONCLUSIONS: The
      findings suggest that the double unilimb Z-plasty technique is a good alternative
      to address the whistler deformity related to the unilateral cleft lip primary
      repair. This is a simple method, easy to perform by surgeons, for whistler
      deformity management in unilateral cleft lip patients.

PMID- 24322646
TI  - Closed traumatic rupture of the thenar muscles from the origin: a case report and
      review of the literature.
AB  - Closed traumatic rupture of the thenar muscles is an unusual and rare injury.
      Traumatic musculotendinous injuries in the hand and wrist occur primarily from
      penetrating trauma. Only 2 such cases were identified in medical literature. We
      report a case of closed traumatic rupture of the thenar muscles in an otherwise
      healthy 33-year-old female nurse who sustained a hyperabduction injury of her
      right thumb and wrist during a daily occupational routine, resulting in complete
      avulsion of the right abductor pollicis brevis and opponens pollicis from their
      origins. After declining initial surgical management, the patient subsequently
      returned 6 months later reporting continued pain, paresthesias, and thenar
      deformation, and requested surgical intervention. On examination, she continued
      to exhibit weakness of thumb abduction and mild weakness with opposition. She was
      again offered an open carpal tunnel release with exploration of the thenar
      eminence and possible tendon transfer, although she adamantly refused any tendon
      transfer. An open right carpal tunnel release was performed with exploration and
      direct muscle repair through a lateral thenar incision. Primary muscular
      reattachment was accomplished by suturing the abductor pollicis brevis and
      opponens pollicis to the flexor retinaculum and the trapezium. Functional results
      15 months after surgery were satisfactory with improvements in abduction and
      opposition of the thumb and restoration of the thenar contour. The chosen
      surgical technique for repair resulted in good functional outcome, while avoiding
      the need for tendon transfer. 

PMID- 24322647
TI  - A study on the measurement of wrist motion range using the iPhone 4 gyroscope
      application.
AB  - INTRODUCTION: Measuring the range of motion (ROM) of the wrist is an important
      physical examination conducted in the Department of Hand Surgery for the purpose
      of evaluation, diagnosis, prognosis, and treatment of patients. The most common
      method for performing this task is by using a universal goniometer. MATERIALS AND
      METHODS: This study was performed using 52 healthy participants to compare wrist
      ROM measurement using a universal goniometer and the iPhone 4 Gyroscope
      application. Participants did not have previous wrist illnesses and their
      measured values for wrist motion were compared in each direction. RESULTS: Normal
      values for wrist ROM are 73 degrees of flexion, 71 degrees of extension, 19
      degrees of radial deviation, 33 degrees of ulnar deviation, 140 degrees of
      supination, and 60 degrees of pronation.The average measurement values obtained
      using the goniometer were 74.2 (5.1) degrees for flexion, 71.1 (4.9) degrees for
      extension, 19.7 (3.0) degrees for radial deviation, 34.0 (3.7) degrees for ulnar
      deviation, 140.8 (5.6) degrees for supination, and 61.1 (4.7) degrees for
      pronation. The average measurement values obtained using the iPhone 4 Gyroscope
      application were 73.7 (5.5) degrees for flexion, 70.8 (5.1) degrees for
      extension, 19.5 (3.0) degrees for radial deviation, 33.7 (3.9) degrees for ulnar
      deviation, 140.4 (5.7) degrees for supination, and 60.8 (4.9) degrees for
      pronation. The differences between the measurement values by the Gyroscope
      application and average value were 0.7 degrees for flexion, -0.2 degrees for
      extension, 0.5 degrees for radial deviation, 0.7 degrees for ulnar deviation, 0.4
      degrees for supination, and 0.8 degrees for pronation. The differences in average
      value were not statistically significant. CONCLUSIONS: The authors introduced a
      new method of measuring the range of wrist motion using the iPhone 4 Gyroscope
      application that is simpler to use and can be performed by the patient outside a
      clinical setting.

PMID- 24322648
TI  - Obesity: New strategy for diet-induced obesity.

PMID- 24322649
TI  - Neuroendocrine tumours: the role of imaging for diagnosis and therapy.
AB  - In patients with neuroendocrine tumours (NETs), a combination of morphological
      imaging and nuclear medicine techniques is mandatory for primary tumour
      visualization, staging and evaluation of somatostatin receptor status. CT and MRI
      are well-suited for discerning small lesions that might escape detection by
      single photon emission tomography (SPECT) or PET, as well as for assessing the
      local invasiveness of the tumour or the response to therapy. Somatostatin
      receptor imaging, by (111)In-pentetreotide scintigraphy or PET with (68)Ga
      labelled somatostatin analogues, frequently identifies additional lesions that
      are not visible on CT or MRI scans. Currently, somatostatin receptor scintigraphy
      with (111)In-pentetreotide is the more frequently available of the two techniques
      to determine somatostatin receptor expression and is needed to select patients
      for peptide receptor radionuclide therapy. In the future, because of its higher
      sensitivity, PET with (68)Ga-labelled somatostatin analogues is expected to
      replace somatostatin receptor scintigraphy. Whereas (18)F-FDG-PET is only used in
      high-grade neuroendocrine cancers, PET-CT with (18)F-dihydroxy-L-phenylalanine or
      (11)C-5-hydroxy-L-tryptophan is a useful problem-solving tool and could be
      considered for the evaluation of therapy response in the future. This article
      reviews the role of imaging for the diagnosis and management of intestinal and
      pancreatic NETs. Response evaluation and controversies in NET imaging will also
      be discussed. 

PMID- 24322651
TI  - Type 2 diabetes mellitus in 2013: A central role of the gut in glucose
      homeostasis.
AB  - Metabolic surgery has been proven to be effective in inducing remission of type 2
      diabetes mellitus prior to any significant weight reduction. Studies in 2013 have
      investigated the mechanisms of action of these procedures and have highlighted a
      central role of the small intestine in the effects on glucose homeostasis.

PMID- 24322650
TI  - Thyroid hormones and skeletal muscle--new insights and potential implications.
AB  - Thyroid hormone signalling regulates crucial biological functions, including
      energy expenditure, thermogenesis, development and growth. The skeletal muscle is
      a major target of thyroid hormone signalling. The type 2 and 3 iodothyronine
      deiodinases (DIO2 and DIO3, respectively) have been identified in skeletal
      muscle. DIO2 expression is tightly regulated and catalyses outer-ring
      monodeiodination of the secreted prohormone tetraiodothyronine (T4) to generate
      the active hormone tri-iodothyronine (T3). T3 can remain in the myocyte to signal
      through nuclear receptors or exit the cell to mix with the extracellular pool. By
      contrast, DIO3 inactivates T3 through removal of an inner-ring iodine. Regulation
      of the expression and activity of deiodinases constitutes a cell-autonomous, pre
      receptor mechanism for controlling the intracellular concentration of T3. This
      local control of T3 activity is crucial during the various phases of myogenesis.
      Here, we review the roles of T3 in skeletal muscle development and homeostasis,
      with a focus on the emerging local deiodinase-mediated control of T3 signalling.
      Moreover, we discuss these novel findings in the context of both muscle
      homeostasis and pathology, and examine how skeletal muscle deiodinase activity
      might be therapeutically harnessed to improve satellite-cell-mediated muscle
      repair in patients with skeletal muscle disorders, muscle atrophy or injury. 

PMID- 24322652
TI  - Metabolism in 2013: The gut microbiota manages host metabolism.
AB  - In 2013, studies in rodents and humans have reaffirmed the essential role of the
      gut microbiota in host metabolism. More importantly, several converging results
      have increased our knowledge regarding the taxa and functions of the gut
      microbiota that contribute to the management of energy homeostasis, glucose
      metabolism and metabolic inflammation.

PMID- 24322653
TI  - Reproductive endocrinology: New guidelines for the diagnosis and treatment of
      PCOS.
AB  - An Endocrine Society-appointed task force has developed an evidence-based
      clinical practice guideline for the diagnosis and treatment of polycystic ovary
      syndrome. The guidelines provide suggestions for the management of patients with
      polycystic ovary syndrome and highlight many areas of uncertainty requiring
      further scientific efforts.

PMID- 24322654
TI  - Nutrition: Consuming nuts frequently might help extend life.

PMID- 24322655
TI  - Immigrant Arab Americans and alcohol use: longitudinal study.
AB  - English proficiency is associated with alcohol use in some immigrants groups, but
      little is known about its association among Arab Americans. Ethnographic work
      suggests gender, religion, education, and age influence prevalence of alcohol use
      among Arab Americans. Two years prospective study of recent Iraqi refugees and
      non-Iraqi Arab immigrants in Michigan using bilingual surveys and interviewers.
      At Time 1, prevalence of lifetime alcohol use was 20.5 % with males, Christians,
      better educated, older, and those with greater proficiency in English more likely
      to report ever drank. At Time 2, lifetime prevalence of drinking had increased to
      34.0 %. In analysis of male new drinkers, risk factors were Christian, older age
      and greater proficiency in English. This study confirms drinking among recent
      immigrant Arab Americans varies by subgroups and suggests English proficiency may
      contribute to the increase in prevalence over time. 

PMID- 24322656
TI  - Impaired reflexive orienting to social cues in attention deficit hyperactivity
      disorder.
AB  - The present study investigated whether another person's social attention,
      specifically the direction of their eye gaze, and non-social directional cues
      triggered reflexive orienting in individuals with Attention Deficit Hyperactivity
      Disorder (ADHD) and age-matched controls. A choice reaction time and a detection
      tasks were used in which eye gaze, arrow and peripheral cues correctly
      (congruent) or incorrectly (incongruent) signalled target location. Independently
      of the type of the task, differences between groups were specific to the cue
      condition. Typically developing individuals shifted attention to the location
      cued by both social and non-social cues, whereas ADHD group showed evidence of
      reflexive orienting only to locations previously cued by non-social stimuli
      (arrow and peripheral cues) but failed to show such orienting effect in response
      to social eye gaze cues. The absence of reflexive orienting effect for eye gaze
      cues observed in the participants with ADHD may reflect an attentional impairment
      in responding to socially relevant information. 

PMID- 24322657
TI  - Oral antibiotics and the management of chronic sinusitis: what do we know?
AB  - PURPOSE OF REVIEW: Chronic rhinosinusitis affected 12.5% of the general
      population in the United States, making it one of the most common causes for
      patients to seek medical care. Despite a lack of compelling evidence, antibiotics
      are the most frequently prescribed class of medications for the treatment of
      chronic sinusitis, demonstrating a deeply rooted belief that bacteria are in some
      way responsible for the disease. RECENT FINDINGS: Despite the high prevalence of
      sinusitis, the cause of chronic rhinosinusitis remains elusive despite multiple
      attempts to determine the underlying cause. Theories have come and gone
      throughout the years with fungi, bacteria, host immunological defects, allergy,
      structural and functional defects, gastroesophageal reflux disease, environmental
      chemicals, and bacterial biofilms being blamed for this chronic inflammatory
      state of the sinonasal mucosa. Recent literature has continued to explore these
      various theories. SUMMARY: To date, there is no high-quality evidence that
      antibiotic therapy has any effect on the long-term management of chronic
      rhinosinusitis. No randomized placebo-controlled studies evaluating the utility
      of antibiotics have as yet been conducted. There remains an urgent need for a
      high-quality, prospective clinical trial to determine the proper role of
      antibiotics in the treatment of chronic rhinosinusitis.

PMID- 24322658
TI  - Does human papilloma virus play a role in sinonasal inverted papilloma?
AB  - PURPOSE OF REVIEW: Inverted papillomas are a benign sinonasal tumor with a
      propensity for recurrence and malignant transformation. Although many
      investigations have been made into the nature of this disease, its etiology and
      causes for malignant transformation have yet to be fully elucidated. It is the
      authors' objective to present a review on management of the disease and evaluate
      the present relationship between human papilloma virus (HPV) and inverted
      papilloma. RECENT FINDINGS: A causal relationship between HPV and the
      pathogenesis and progression of inverted papilloma has been posited since the
      1980s. Although widely varied HPV detection rates have been reported, recent
      studies have noted a substantial increase in both recurrence and malignant
      transformation in HPV-infected inverted papillomas. However, exact cellular
      mechanisms by which infection leads to subsequent recurrence and development of
      carcinoma have yet to be elucidated. SUMMARY: Evidence exists suggesting that HPV
      infection plays a role in the progression of inverted papilloma and confers an
      increased risk for recurrence and malignant transformation. PCR is the preferred
      detection method, and fresh or frozen specimens are the ideal source of tissue
      for evaluation. Although multiple studies have detected an association between
      HPV and inverted papilloma (both recurrent and malignant transformation), further
      studies are necessary to elucidate the underlying molecular pathways before an
      association can be changed to causation.

PMID- 24322660
TI  - Yttrium-substituted nanocrystalline TiO2 photoanodes for perovskite based
      heterojunction solar cells.
AB  - We report the use of Y(3+)-substituted TiO2 (0.5%Y-TiO2) in solid-state
      mesoscopic solar cells, consisting of CH3NH3PbI3 as the light harvester and spiro
      OMeTAD as the hole transport material. A power conversion efficiency of 11.2%
      under simulated AM 1.5 full sun illumination was measured. A 15% improvement in
      the short-circuit current density was obtained compared with pure TiO2, due to
      the effect of Y(3+) on the dimensions of perovskite nanoparticles formed on the
      semiconductor surface, showing that the surface modification of the semiconductor
      is an effective way to improve the light harvesters' morphology and electron
      transfer properties in the solid-state mesoscopic solar cells.

PMID- 24322659
TI  - Metformin selectively targets tumor-initiating cells in ErbB2-overexpressing
      breast cancer models.
AB  - Metformin is an oral biguanide used for type II diabetes. Epidemiologic studies
      suggest a link between metformin use and reduced risk of breast and other types
      of cancers. ErbB2-expressing breast cancer is a subgroup of tumors with poor
      prognosis. Previous studies demonstrated that metformin is a potent inhibitor of
      ErbB2-overexpressing breast cancer cells; metformin treatment extends the life
      span and impedes mammary tumor development in ErbB2 transgenic mice in vivo.
      However, the mechanisms of metformin associated antitumor activity, especially in
      prevention models, remain unclear. We report here for the first time that
      systemic administration of metformin selectively inhibits CD61(high)/CD49f(high)
      subpopulation, a group of tumor-initiating cells (TIC) of mouse mammary tumor
      virus (MMTV)-ErbB2 mammary tumors, in preneoplastic mammary glands. Metformin
      also inhibited CD61(high)/CD49f(high) subpopulation in MMTV-ErbB2 tumor-derived
      cells, which was correlated with their compromised tumor initiation/development
      in a syngeneic tumor graft model. Molecular analysis indicated that metformin
      induced downregulation of ErbB2 and EGFR expression and inhibited the
      phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR,
      and STAT3 in vivo. In vitro data indicate that low doses of metformin inhibited
      the self-renewal/proliferation of cancer stem cells (CSC)/TICs in ErbB2
      overexpressing breast cancer cells. We further demonstrated that the expression
      and activation of ErbB2 were preferentially increased in CSC/TIC-enriched
      tumorsphere cells, which promoted their self-renewal/proliferation and rendered
      them more sensitive to metformin. Our results, especially the in vivo data,
      provide fundamental support for developing metformin-mediated preventive
      strategies targeting ErbB2-associated carcinogenesis.

PMID- 24322662
TI  - In brief: prevention of meningococcus B disease.

PMID- 24322661
TI  - Maternal high-fat diet induces hyperproliferation and alters Pten/Akt signaling
      in prostates of offspring.
AB  - Developing recommendations for prostate cancer prevention requires identification
      of modifiable risk factors. Maternal exposure to high-fat diet (HFD) initiates a
      broad array of second-generation adult disorders in murine models and humans.
      Here, we investigate whether maternal HFD in mice affects incidence of prostate
      hyperplasia in offspring. Using three independent assays, we demonstrate that
      maternal HFD is sufficient to initiate prostate hyperproliferation in adult male
      offspring. HFD-exposed prostate tissues do not increase in size, but instead
      concomitantly up-regulate apoptosis. Maternal HFD-induced phenotypes are focally
      present in young adult subjects and greatly exacerbated in aged subjects. HFD
      exposed prostate tissues additionally exhibit increased levels of activated Akt
      and deactivated Pten. Taken together, we conclude that maternal HFD diet is a
      candidate modifiable risk factor for prostate cancer initiation in later life. 

PMID- 24322663
TI  - MiniMed 530G: an insulin pump with low-glucose suspend automation.

PMID- 24322664
TI  - Pertuzumab (Perjeta) for preoperative use in HER2-positive breast cancer.

PMID- 24322665
TI  - Ferric carboxymaltose (Injectafer) for iron deficiency anemia.

PMID- 24322666
TI  - Supramolecular charge transfer nanostructures.
AB  - Supramolecular organization of pi-conjugated chromophores into well defined
      nanostructures has gained much attention due to their promising role as active
      components in organic electronics. Charge-transfer (CT) nanostructures, in which
      aromatic donor (D) and acceptor (A) molecules are alternately arranged, (mixed
      stack) have emerged recently as prospective candidates in this direction, because
      they provide inherent, uniform doping conducive for excellent conducting
      properties. The present perspective highlights the importance of charge transfer
      (CT) based non-covalent interactions, with emphasis on supramolecular design
      principles, for construction of various CT nano-architectures. The whole article
      is divided into three parts themed on the type of interactions used for obtaining
      CT assemblies. Through some of our recent results, we have attempted to highlight
      the latent potential of this nascent field. Furthermore, we have presented our
      perspectives on the major challenges in this field which is expected to broaden
      the scope of this subject. 

PMID- 24322667
TI  - Specific impairments in instrumental learning following chronic intermittent
      toluene inhalation in adolescent rats.
AB  - RATIONALE: Inhalant abuse is prevalent in adolescent populations, with chronic
      use resulting in neurobiological and cognitive abnormalities in adulthood.
      However, the nature and persistence of cognitive dysfunction, particularly
      following adolescent inhalant abuse, remain equivocal. OBJECTIVE: The present
      study assessed specific cognitive processes beginning in late adolescence and
      adulthood following adolescent inhalation of toluene, a main component of many
      compounds readily abused. METHODS: Adolescent male Wistar rats (postnatal day
      (PN) 27) were exposed to chronic intermittent inhaled toluene (10,000 ppm) for 1
      h/day, 3 days/week for 4 weeks (PN 27-52) to mimic the patterns observed in human
      adolescent inhalant abusers. Following toluene exposure, motor and cognitive
      function was assessed. RESULTS: Adolescent toluene exposure did not alter motor
      learning in the Rotarod task (PN 58) or acquisition, reversal, or retention of
      spatial learning in the Morris water maze (PN 55-64). In contrast, it delayed
      acquisition of instrumental responding for sucrose (5 % w/v) and impaired operant
      reversal learning and cue-induced reinstatement of sucrose seeking in adulthood
      (PN 57-100). CONCLUSION: This study demonstrates that exposure to toluene at an
      abuse concentration during adolescence results in specific impairments in aspects
      of instrumental learning, without altering motor function and spatial learning in
      late adolescence/early adulthood. Our data imply that persistent alterations in
      reward processing may occur following adolescent inhalant misuse.

PMID- 24322669
TI  - Oral contraceptives and sexual desire: replies to Graham and Bancroft (2013) and
      Puts and Pope (2013).

PMID- 24322668
TI  - Pediatric thymomas: report of two cases and comprehensive review of the
      literature.
AB  - PURPOSE: Thymomas are rare pediatric malignancies with indolent behavior. There
      are fewer than 50 reported cases and no comprehensive review. We sought to
      evaluate our recent experience with pediatric thymomas, and comprehensively
      review the extant literature. METHODS: A systematic search of the PubMed database
      was performed using keywords: "thymoma", "pediatric", "juvenile", "childhood",
      and "child". Additional studies were identified by a manual search of the
      reference list. RESULTS: We report two patients with thymomas. We identified 22
      case reports or series that described 48 patients; 62 % were male, 15 % presented
      with myasthenia gravis. Fifty percent were Masaoka Stage I, 15 % were Stage II,
      13 % were Stage III, and 23 % were Stage IV. Four patients with early stage (I or
      II) disease were treated with adjuvant therapies in addition to surgical
      excision, while five patients with late stage (III or IV) disease treated with
      surgical excision alone. Of studies reporting at least 2-year follow-up, survival
      was 71 %. CONCLUSION: Pediatric thymomas are rare tumors with a slight male
      predominance. Wide variations were observed in the treatment of thymomas across
      all stages. Our review indicates a need for large database and multi
      institutional studies to clearly elucidate clinical course, prognostic factors
      and outcome.

PMID- 24322670
TI  - Drug use and sexual arrangements among gay couples: frequency, interdependence,
      and associations with sexual risk.
AB  - Rates of drug use among gay men are higher than their heterosexual counterparts
      and drug use is a prominent risk factor for HIV transmission. Studies using
      heterosexual samples have found that being partnered reduces the risk of drug use
      and individuals in a relationship tend to have similar use patterns. Studies
      among gay men suggest that sexual agreements may be an important predictor of
      drug use. Data from 322 partnered gay men were collected and the 161 matched
      couples were categorized as monogamous (52.8 %), monogamish (14.9 %), open (13.0
      %), and discrepant (19.3 %). Patterns of significance and significant trends
      suggested that monogamous men reported lower rates of marijuana and other drug
      use compared to open and monogamish men. Men in discrepant relationships did not
      differ from any other group. Partners' marijuana and other drug use was
      significantly interdependent in the overall sample; however, substantial
      variation in the magnitude and significance of interdependence was observed
      across sexual arrangement categories. Sexual arrangement and the use of drugs
      during sex both contributed to the prediction of UAI with casual partners among
      non-monogamous men. Implications for substance use treatment and HIV prevention
      are discussed. 

PMID- 24322671
TI  - Chronic concern over an acute-phase reactant: a teachable moment.

PMID- 24322673
TI  - Contribution of time of drinking onset and family history of alcohol problems in
      alcohol and drug use behaviors in Argentinean college students.
AB  - AIMS: The aim of the study was to analyze independent and potential interactive
      effects of age at drinking onset and family history of alcohol abuse on
      subsequent patterns of alcohol drinking, alcohol-related problems and substance
      use. METHODS: Participants were college students (60.3% females, mean age = 20.27
      +/- 2.54 years) from the city of Cordoba, Argentina. Several measures were used
      to assess alcohol, tobacco and drug use. The Spanish version of the Brief Young
      Adult Alcohol Consequences Questionnaire was used to assess alcohol-related
      problems. Factorial analyses of variance, or its non-parametric equivalent, were
      performed to explore differences in substance use behaviors and alcohol-related
      problems in subjects with early or late drinking onset and with or without family
      history of alcohol abuse. Chi-square tests were conducted to analyze the
      association between these two risk factors and categorical measures of alcohol,
      tobacco and drug use. RESULTS: Early onset of drinking was associated with amount
      of consumption of alcohol including up to hazardous levels, as well as tobacco
      and drug use. However, the frequency of alcohol problems and frequency of
      episodes of alcohol intoxication were only related to age of onset in those with
      a positive family history of alcohol problems. CONCLUSION: Delaying drinking
      debut is particularly important in the prevention of future alcohol problems in
      those adolescents who have a family history of such problems.

PMID- 24322674
TI  - Follicular erythematous papules with keratotic spicules: a quiz. Trichodysplasia
      spinulosa.

PMID- 24322672
TI  - Transcriptional signaling pathways inversely regulated in Alzheimer's disease and
      glioblastoma multiform.
AB  - Convincing epidemiological data suggest an inverse association between cancer and
      neurodegeneration, including Alzheimer's disease (AD). Since both AD and cancer
      are characterized by abnormal, but opposing cellular behavior, i.e., increased
      cell death in AD while excessive cell growth occurs in cancer, this motivates us
      to initiate the study into unraveling the shared genes and cell signaling
      pathways linking AD and glioblastoma multiform (GBM). In this study, a
      comprehensive bioinformatics analysis on clinical microarray datasets of 1,091
      GBM and 524 AD cohorts was performed. Significant genes and pathways were
      identified from the bioinformatics analyses - in particular ERK/MAPK signaling,
      up-regulated in GBM and Angiopoietin Signaling pathway, reciprocally up-regulated
      in AD - connecting GBM and AD (P < 0.001), were investigated in details for their
      roles in GBM growth in an AD environment. Our results showed that suppression of
      GBM growth in an AD background was mediated by the ERK-AKT-p21-cell cycle pathway
      and anti-angiogenesis pathway.

PMID- 24322675
TI  - Fulfilling a need: a 20-year focus on public health practice.

PMID- 24322676
TI  - Transforming public health practice through accreditation (a user guide for the
      special accreditation issue).

PMID- 24322677
TI  - Overview of the public health accreditation board.

PMID- 24322678
TI  - PHAB: reflections from the first year of accreditation.

PMID- 24322679
TI  - A consensus-based approach to national public health accreditation.
AB  - The Public Health Accreditation Board (PHAB) solicited (and continues to solicit)
      the input of more than 400 subject matter experts in various areas of public
      health during the development and ongoing revision of the accreditation standards
      and measures. This process is designed to ensure that the standards and measures
      remain relevant and accommodate the various contexts under which public health
      departments practice in the United States. One way PHAB gathers feedback is
      convening a series of discussion meetings, or think tanks, with thought leaders
      in specific areas of public health, that focus on specific programmatic areas of
      public health, on the broader context of public health practice, or on emerging
      issues, such as public health informatics. The think tanks complement other
      mechanisms to assure that standards and measures are relevant, including
      gathering input from the practice community, receiving recommendations from
      public health departments that have undergone the accreditation process, and
      reviewing relevant literature. While this process allows PHAB to demonstrate its
      commitment to continuous quality improvement by modifying and improving the
      standards and measures, it also serves as a communication vehicle for PHAB to
      educate thought leaders and public health practitioners about the national
      accreditation program. 

PMID- 24322680
TI  - CDC/NACCHO Accreditation Support Initiative: advancing readiness for local and
      tribal health department accreditation.
AB  - CONTEXT: Health departments have various unique needs that must be addressed in
      preparing for national accreditation. These needs require time and resources,
      shortages that many health departments face. OBJECTIVE: The Accreditation Support
      Initiative's goal was to test the assumption that even small amounts of dedicated
      funding can help health departments make important progress in their readiness to
      apply for and achieve accreditation. DESIGN: Participating sites' scopes of work
      were unique to the needs of each site and based on the proposed activities
      outlined in their applications. Deliverables and various sources of data were
      collected from sites throughout the project period (December 2011-May 2012).
      SETTING/PARTICIPANTS: Awardees included 1 tribal and 12 local health departments,
      as well as 5 organizations supporting the readiness of local and tribal health
      departments. RESULTS: Sites dedicated their funding toward staff time,
      accreditation fees, completion of documentation, and other accreditation
      readiness needs and produced a number of deliverables and example documents. All
      sites indicated that they made accreditation readiness gains that would not have
      occurred without this funding. CONCLUSIONS: Preliminary evaluation data from the
      first year of the Accreditation Support Initiative indicate that flexible funding
      arrangements may be an effective way to increase health departments'
      accreditation readiness.

PMID- 24322681
TI  - Supporting accreditation in tribal settings.

PMID- 24322682
TI  - Improving public health through state health improvement planning: a framework
      for action.
AB  - BACKGROUND: State health improvement plans (SHIPs) identify priorities for making
      the greatest impacts on health promotion and disease prevention, specific to the
      needs of state populations. Both SHIPs and the state health assessments on which
      they are based are prerequisites for Public Health Accreditation Board national
      accreditation. OBJECTIVE: To identify and evaluate existing SHIPs to develop
      guidance to support health departments in the state health improvement planning
      process. DESIGN: In 2010, the Association of State and Territorial Health
      Officials (ASTHO) conducted a comprehensive search for existing SHIPs. A
      systematic evaluation of existing SHIPS was accomplished by means of primary
      source document review using a standardized data collection form. Using data
      derived from these SHIPs and guidance from a workgroup of practitioners, ASTHO
      developed the ASTHO SHIP Guidance and Resources (SHIP Guidance) Framework.
      RESULTS: The search yielded 25 states (49%) having a SHIP completed or in
      progress. Fifteen states (29%) had no SHIP but had a Healthy People plan, and 10
      states (20%) had no SHIP or Healthy People plan. No information was available for
      1 state. Findings were reviewed, evaluated, and incorporated into the SHIP
      Guidance. The SHIP Guidance provides a framework for the implementation,
      monitoring, and evaluation of a SHIP process using 12 key steps. CONCLUSIONS: As
      public health/health care integration and accreditation readiness activity grows,
      multisector engagement through a SHIP will continue to be a priority for state
      public health and improving health outcomes. The SHIP Guidance provides a
      systematic, flexible approach for states conducting or updating state health
      assessments and SHIPs.

PMID- 24322684
TI  - Advancing accreditation through the National Public Health Improvement
      Initiative.

PMID- 24322683
TI  - Advances in public health accreditation readiness and quality improvement:
      evaluation findings from the National Public Health Improvement Initiative.
AB  - INTRODUCTION: Continuous quality improvement is a central tenet of the Public
      Health Accreditation Board's (PHAB) national voluntary public health
      accreditation program. Similarly, the Centers for Disease Control and Prevention
      launched the National Public Health Improvement Initiative (NPHII) in 2010 with
      the goal of advancing accreditation readiness, performance management, and
      quality improvement (QI). OBJECTIVE: Evaluate the extent to which NPHII awardees
      have achieved program goals. DESIGN: NPHII awardees responded to an annual
      assessment and program monitoring data requests. Analysis included simple
      descriptive statistics. SETTING: Seventy-four state, tribal, local, and
      territorial public health agencies receiving NPHII funds. PARTICIPANTS: NPHII
      performance improvement managers or principal investigators. MAIN OUTCOME
      MEASURE(S): Development of accreditation prerequisites, completion of an
      organizational self-assessment against the PHAB Standards and Measures, Version
      1.0, establishment of a performance management system, and implementation of QI
      initiatives to increase efficiency and effectiveness. RESULTS: Of the 73
      responding NPHII awardees, 42.5% had a current health assessment, 26% had a
      current health improvement plan, and 48% had a current strategic plan in place at
      the end of the second program year. Approximately 26% of awardees had completed
      an organizational PHAB self-assessment, 72% had established at least 1 of the 4
      components of a performance management system, and 90% had conducted QI
      activities focused on increasing efficiencies and/or effectiveness. CONCLUSIONS:
      NPHII appears to be supporting awardees' initial achievement of program outcomes.
      As NPHII enters its third year, there will be additional opportunities to advance
      the work of NPHII, compile and disseminate results, and inform a vision of high
      quality public health necessary to improve the health of the population.

PMID- 24322685
TI  - Sustaining a quality improvement culture in local health departments applying for
      accreditation.
AB  - CONTEXT: This article focuses on local health departments (LHDs) that are
      advanced in accreditation and quality improvement (QI) efforts and the barriers
      and facilitators associated with sustaining improvements and building an
      organizational culture of QI. OBJECTIVE: To understand the barriers and
      facilitators associated with building and sustaining progress toward a QI culture
      in LHDs. DESIGN: Quantitative data from a self-reporting survey and qualitative
      data from telephone interviews. SETTING: Twenty-two LHDs across the United States
      responded to the survey. Ten of the 22 LHD respondents participated in telephone
      interviews. PARTICIPANTS: QI lead staff at LHDs that are advanced in
      accreditation preparation and QI. MAIN OUTCOME MEASURES: Self-reported LHD survey
      ratings against indicators for a QI culture, and the identified barriers and
      facilitators around sustaining QI initiatives. RESULTS: Of the 6 domains of a QI
      culture measured in the survey, the percentages of respondents that scored
      themselves highly to at least 1 indicator in each domain are as follows:
      leadership commitment (100%); employee empowerment (100%); teamwork and
      collaboration (100%); continuous process improvement (86%); customer focus (72%);
      and QI infrastructure (64%). Qualitative data from 10 telephone interviews
      revealed that key barriers to sustaining progress around QI included staff
      turnover, budget cuts, and major crises or events that arise as priority. Key
      facilitators included leadership commitment, accreditation, and dedication of
      resources and staff time to QI. CONCLUSIONS: When engaging in QI, LHDs should
      consider investing efforts in gaining leadership support and dedicating staff
      time early in the QI journey to ensure that QI efforts and initiatives are
      sustained. Local health departments interested in developing a QI culture should
      also consider pursuing accreditation, as it provides a structured framework for
      continuous improvement. They should also actively develop QI knowledge and skills
      among all staff members to minimize the negative impact of staff turnover.

PMID- 24322686
TI  - Using quality improvement tools and methods throughout the accreditation
      lifecycle.

PMID- 24322687
TI  - Quality improvement coaching to build capacity within health departments:
      reflections and recommendations.
AB  - CONTEXT: Strengthening the Community of Practice for Public Health Improvement is
      a 2-year initiative that facilitates the exchange of best practices and builds
      capacity among the nation's health departments to become accredited and conduct
      quality improvement (QI). Launched as the Public Health Accreditation Board
      opened its doors to receive the first accreditation applications from health
      departments, the Community of Practice for Public Health Improvement is the next
      stage in the National Network of Public Health Institutes' efforts to nurture and
      expand a community of practice focused on accreditation and QI. A key component
      of the Community of Practice for Public Health Improvement is the QI Award
      Program, which provides small grants and distance-based QI coaching to state,
      local, tribal, and territorial health departments. OBJECTIVE: To understand the
      efficacy of distance-based QI coaching. DESIGN: The QI coaching model was
      evaluated using Web-based satisfaction surveys along with programmatic data
      collected through progress reports, coaching logs, and meetings. SETTING: During
      2 QI Award Program cycles, 60 health departments (30 departments per cycle)
      received $5000 and QI coaching to engage in QI projects that address locally
      identified priorities and connect to efforts to prepare for public health
      accreditation. PARTICIPANTS: Data in this article represent findings from the
      first 30 sites and 9 coaches who participated in cycle 1. MAIN OUTCOME
      MEASURE(S): QI coaching hours and methods, sites' impressions of QI coaching,
      sites' accomplishments due to coaching, and suggestions for coaching improvement.
      RESULTS: Approximately 80% of QI satisfaction survey respondents indicated that
      they strongly agreed or agreed that distance-based coaching is effective. Sites
      also reported increased experience with QI processes, initiation of QI spread
      within the health department, and additional activity within and beyond the
      project team due to the QI Award Program.

PMID- 24322688
TI  - Embedding quality improvement into accreditation: evolving from theory to
      practice.

PMID- 24322689
TI  - Instrumental roles of governance in accreditation: responsibilities of public
      health governing entities.

PMID- 24322690
TI  - Introduction to case reports: one goal-many journeys.

PMID- 24322691
TI  - New Orleans Health Department: using the accreditation framework to transform a
      local health department.

PMID- 24322692
TI  - Oklahoma State Department of Health: insights from a newly Accredited State
      Health Department.

PMID- 24322693
TI  - Norwalk Health Department: coleading a community health assessment and
      improvement plan with Norwalk hospital.

PMID- 24322694
TI  - Maine Center for Disease Control and Prevention: accreditation readiness review.

PMID- 24322695
TI  - Cabarrus health alliance: experiences with state and national accreditation.

PMID- 24322696
TI  - Arizona Department of Health Services: achieving early accreditation milestones
      through county collaboration.

PMID- 24322697
TI  - Chicago Department of Public Health: leadership and communication to support
      accreditation.

PMID- 24322698
TI  - New York State Department of Health: approaching the documentation selection
      process from an improvement perspective.

PMID- 24322699
TI  - Missoula city-County Health Department: accreditation preparation in the
      preapplication phase.

PMID- 24322700
TI  - Oregon public health division: building a collaborative approach to accreditation
      across a state public health system.

PMID- 24322701
TI  - Tooele County Health Department: building on the Beta test to prepare for
      accreditation.

PMID- 24322702
TI  - A study of incentives to support and promote public health accreditation.
AB  - CONTEXT: Accreditation of public health agencies through the Public Health
      Accreditation Board is voluntary. Incentives that encourage agencies to apply for
      accreditation have been suggested as important factors in facilitating
      participation by state and local agencies. OBJECTIVE: The project describes both
      current and potential incentives that are available at the federal, state, and
      local levels. DESIGN: Thirty-nine key informants from local, state, tribal,
      federal, and academic settings were interviewed from March through May 2012.
      Through open-ended interviews, respondents were asked about incentives that were
      currently in use in their settings and incentives they thought would help
      encourage participation in Public Health Accreditation Board accreditation.
      RESULTS: Incentives currently in use by public health agencies based on
      interviews include (1) financial support, (2) legal mandates, (3) technical
      assistance, (4) peer support workgroups, and (5) state agencies serving as role
      models by seeking accreditation themselves. Key informants noted that state
      agencies are playing valuable and diverse roles in providing incentives for
      accreditation within their own states. Key informants also identified the Centers
      for Disease Control and Prevention and other players, such as private
      foundations, public health institutes, national and state associations, and
      academia as providing both technical and financial assistance to support
      accreditation efforts. CONCLUSIONS: State, tribal, local, and federal agencies,
      as well as related organizations can play an important role by providing
      incentives to move agencies toward accreditation.

PMID- 24322703
TI  - Guiding the way to public health improvement: exploring the connections between
      The Community Guide's Evidence-Based Interventions and health department
      accreditation standards.
AB  - CONTEXT: Recent years have seen rising interest in initiatives that focus on
      public health improvement. This includes support for accreditation of public
      health departments-administered by the Public Health Accreditation Board (PHAB)
      and increasing expectations that health departments should use evidence-based
      programs, services, and policies (interventions) such as those described in The
      Guide to Community Preventive Services (The Community Guide). OBJECTIVE: This
      project was initiated to explore the potential connections between Community
      Guide interventions and PHAB domains, standards, and measures. DESIGN: The
      project team focused on developing a Crosswalk tool to assist health departments
      in identifying evidence-based interventions from The Community Guide whose
      implementation could help document conformity with PHAB domains, standards, and
      measures. All Community Preventive Services Task Force-recommended interventions
      were reviewed to determine whether they reflect the intent and requirements of
      the PHAB standards and measures. MAIN OUTCOME MEASURES: Three types of
      connections were defined through which Community Guide interventions could be
      relevant to the required documentation for a PHAB measure. All instances of these
      connections were identified and included in the Crosswalk. RESULTS: The Crosswalk
      tool consists of 2 tables. The first table cross-references individual PHAB
      domains, standards, and measures with interventions from The Community Guide that
      could help provide documentation for accreditation. The second table can help
      accreditation preparation staff to engage with program staff. It is searchable by
      Community Guide topic, identifying the PHAB measures that relate to each
      Community Guide intervention within that topic. The type, location, and extent of
      connections between Community Guide interventions and PHAB domains, standards,
      and measures are presented and discussed. CONCLUSIONS: Tools such as the
      Crosswalk can be instrumental in advancing the use of evidence-based
      interventions in public health practice.

PMID- 24322704
TI  - An examination of state laws and policies regarding public health agency
      accreditation prerequisites.
AB  - CONTEXT: The Public Health Accreditation Board (PHAB) began accepting
      applications for national voluntary accreditation in the fall of 2011. There are
      3 prerequisites for accreditation: health assessments; health improvement plans;
      and strategic plans. These prerequisites must be in place for a state or local
      public health agency to apply for PHAB accreditation. Completion of the
      prerequisites can become a barrier for agencies that are considering applying for
      accreditation. OBJECTIVE: This project looked at all 50 states through a legal
      lens to identify legal tools in the form of laws, rules, executive orders,
      contracts, legislative resolutions, and other tools that are used to authorize or
      require that a state or local health agency complete 1 or more of the
      prerequisites. DESIGN: Using legal research platforms and a Boolean search
      stream, an inquiry of legal tools in all 50 states was completed to determine
      where legal tools are used to authorize or require the 3 PHAB prerequisites. Once
      legal tools were found, interviews were conducted with key informants from each
      state to understand the implementation and use of the legal tools found and
      collect any additional legal tools that were not found from the legal search.
      RESULTS: The results include key findings and, importantly, an inventory of laws
      and legal tools that are being used around the country to require and support
      completion of the prerequisites. Within all 50 states, 26 states have some type
      of a mandate regarding 1 or more of the PHAB prerequisites. This includes 1 state
      that includes a mandate for PHAB accreditation. CONCLUSIONS: States use a wide
      variety of legal tools to implement the prerequisites for voluntary
      accreditation. It is important to understand the interpretation, enforcement, and
      support of the laws and legal tools to determine whether the tools have impact in
      individual states.

PMID- 24322705
TI  - Accreditation and emergency preparedness: linkages and opportunities for
      leveraging the connections.
AB  - BACKGROUND: Public health officials must frequently demonstrate the quality and
      value of public health services, especially during challenging fiscal climates.
      One of the ways that public health quality and accountability have been
      demonstrated is through the use of accreditation and standard setting
      initiatives. OBJECTIVE: The objective of this analysis was to identify existing
      alignment opportunities between standards established by the Public Health
      Accreditation Board (PHAB) and the Centers for Disease Control and Prevention's
      (CDC's) public health preparedness (PHP) capabilities in order to optimize and
      leverage the connections for state and local public health professionals. DESIGN:
      During March-May 2012, a PHAB/PHP crosswalk was developed by a research team from
      the CDC's Office for State, Tribal, Local and Territorial Support and Office of
      Public Health Preparedness and Response's Division of State and Local Readiness
      to examine the intersection of the PHP capabilities and the PHAB standards. The
      PHAB/PHP crosswalk used the CDC Public Health Preparedness Capabilities: National
      Standards for State and Local Planning (PHP Capabilities) and the PHAB Standards
      and Measures, Version 1.0 (PHAB Standards) as its source documents. To help
      illustrate the results of the crosswalk, alignment was also depicted through a
      network graph to transform the results into a visual depiction of the linkages
      between PHP capabilities and PHAB standards. RESULTS: The most direct links to
      emergency preparedness were found in PHAB Domains 2 and 5. Opportunities for
      improved alignment were found throughout the standard documents, particularly in
      PHAB Domains 3, 8, and 11. The most direct links to accreditation were found in
      PHP capabilities 1, 2, 3, and 4. CONCLUSIONS: The results highlight the synergy
      between the infrastructure and foundational elements represented by accreditation
      and targeted programmatic activities supported by preparedness funding.

PMID- 24322706
TI  - Workforce standards as part of health department accreditation-necessary but not
      yet sufficient.

PMID- 24322707
TI  - Performance management models for public health: Public Health Accreditation
      Board/Baldrige connections, alignment, and distinctions.
AB  - CONTEXT: The nationally known Malcolm Baldrige Award for Excellence ("Baldrige
      program") recognizes outstanding performance management and is specifically cited
      by the Public Health Accreditation Board (PHAB) as a potential framework for
      PHAB's requisite performance management system. The authors developed a crosswalk
      that identifies alignments between the 2 programs and is a highlight of the Quest
      for Exceptional Performance tool that is intended to help health departments
      capitalize on the connections between the 2 programs. OBJECTIVE: To provide
      deeper insight into the most robust connections between the 2 programs. DESIGN:
      The authors developed a crosswalk by listing the PHAB measures, identifying
      corresponding Baldrige areas to address, and assigning a rating regarding the
      strength of the alignment. Subsequently, they generated a matrix with numerical
      scores reflecting the strength of the PHAB-Baldrige alignments that were then
      analyzed for frequency and strength of alignment by PHAB domain and by Baldrige
      category. PARTICIPANTS: The tool developers and 3 public health leaders with
      experience in the Baldrige program contributed to both the design and the
      analyses. MAIN OUTCOME MEASURES: The measures used reflected both the frequency
      and strength of alignments. RESULTS: Of the 123 alignments identified in the
      crosswalk, 39 were rated as high, 40 as medium, and 44 as low. The strongest
      connections were in the areas of performance management, quality improvement,
      strategic planning, workforce development, assessment and analysis, and customer
      service. CONCLUSIONS: While the areas with the most frequent and strongest
      connections provide the most useful basis for health departments pursuing
      Baldrige recognition or using Baldrige criteria as a framework for performance
      management, all alignments could be considered for both purposes.

PMID- 24322708
TI  - Leveraging the revised National Public Health Performance Standards to meet
      today's ever-changing public health system landscape.

PMID- 24322709
TI  - Cross-jurisdictional approaches to meeting PHAB standards and achieving
      accreditation.

PMID- 24322710
TI  - Institutionalizing Public Health Department Accreditation through CDC
      opportunities.

PMID- 24322711
TI  - Accreditation: a lever for transformation of public health practice.

PMID- 24322712
TI  - Untangling desirable and undesirable variation in public health practice:
      accreditation and research working together.

PMID- 24322713
TI  - Accreditation: on target.

PMID- 24322714
TI  - It is as it does: genital form and function in sex reassignment surgery.
AB  - Surgeons who perform sex reassignment surgeries (SRS) define their goals and
      evaluate their outcomes in terms of two kinds of results: aesthetic and
      functional. Since the neogenitals fashioned through sex reassignment surgeries do
      not enable reproductive function, surgeons must determine what the function of
      the genitals is or ought to be. A review of surgical literature demonstrates that
      questions of what constitute genital form and function, while putatively answered
      in the operating room, are not answerable in the discourses of clinical
      evaluation used to define them. When the genitals--the word itself derived from
      the Latin genitas meaning to beget--are not reproductive, the question of their
      function shifts away from the biological and into other registers: pleasure,
      intimacy, sociality. As condensed sites of meaning and meaning-making around
      which selves, affects, resources, anxieties and futures are organized, the
      genitals signify in excess of the categories of "aesthetic" and "function" that
      surgeons use to assess them. Not reducible to either aesthetics or function, but
      constitutive of them both, this excess appears in surgical texts in the form of
      imagined futures of social and sexual engagement and demonstrates a powerful
      means by which properly sexed bodies are created.

PMID- 24322715
TI  - The role of medical management for acute intravascular hemolysis in patients
      supported on axial flow LVAD.
AB  - Continuous flow left ventricular assist devices (LVADs) are used with good
      outcome. However, acute intravascular hemolysis due to thrombus in the pump
      remains a clinical challenge. We screened for LVAD-related intravascular
      hemolysis among 115 consecutive patients surviving HeartMateII implantation and
      investigated the role of medical therapy in resolving the hemolysis. Hemolytic
      events were identified in 7% of patients, 2-26 months after implant, manifested
      by peak lactate dehydrogenase (LDH) levels >6 times normal. With the institution
      of heparin and enhanced antiplatelet therapy, LDH levels receded rapidly reaching
      a stable trough level near baseline within 2 weeks with the resolution of
      clinical symptoms except in one patient who required additional therapy with
      tissue plasminogen activator (tPA). Complications included transient renal
      failure, one splenic infarct, and a cerebrovascular attack after tPA. The acute
      event of hemolysis resolved with medical therapy, and all were successfully
      discharged. However, recurrent hemolysis was common (6/8 patients over the next 1
      7 months). At the end of follow-up, three patients were transplanted, one patient
      died refusing LVAD exchange for recurrent hemolysis, and 4 remained alive on LVAD
      support. Medical treatment with intensification of anticoagulation can be
      effective in resolving the acute hemolytic event. However, a definitive long-term
      strategy should be planned because the recurrence rate is high. 

PMID- 24322716
TI  - Are dialysis adequacy indices independent of solute generation rate?
AB  - KT/V is by definition independent of solute generation rate. Alternative dialysis
      adequacy indices (DAIs) such as equivalent renal clearance (EKR), standard KT/V
      (stdKT/V), and solute removal index (SRI) are estimated as the ratio of solute
      mass removed to an average solute mass in the body or solute concentration in
      blood; both nominator and denominator in these formulas depend on the solute
      generation rate. Our objective was to investigate whether and under which
      conditions the alternative DAIs are independent of solute generation rate. By
      using general compartment modeling, we show that for the metabolically stable
      patient (in whom the solute generated during the dialysis cycle, typically, 1
      week, is equal to the solute removed from the body), DAIs estimated for the
      dialysis cycle are in general independent of the average solute generation rate
      (although they may depend on the pattern of oscillations in the generation rate).
      However, the alternative adequacy parameters (such as EKR, stdKT/V, and SRI) may
      depend on solute generation rate for metabolically unstable patients. 

PMID- 24322717
TI  - Highly proton conductive nanoporous coordination polymers with sulfonic acid
      groups on the pore surface.
AB  - Three new sulfonated porous coordination polymers (PCPs)/metal-organic frameworks
      (MOFs) have been synthesized using solvothermal methods. These PCPs possess
      porous structures with non-coordinating sulfonic acid groups or sulfonate with
      dimethyl ammonium cations and exhibit high proton conductivity at a low humidity
      of 60% RH (relative humidity) at ambient temperature. 

PMID- 24322718
TI  - Hepatoblastoma state of the art: pathology, genetics, risk stratification, and
      chemotherapy.
AB  - PURPOSE OF REVIEW: As a rare pediatric tumor, hepatoblastoma presents challenges
      to the individual practitioner as no center will see more than a handful of cases
      each year. RECENT FINDINGS: The Children's Hepatic tumor International
      Collaborative (CHIC) effort has fostered international cooperation in this rare
      children's tumor, leading to the establishment of a large international
      collaborative dataset, the CHIC database, which has been interrogated to refine
      risk stratification and inform treatment options. Apace with this effort has been
      the international collaboration of pediatric pathologists working together to
      establish a new international histopathologic consensus classification for
      pediatric liver tumors as a whole, with particular focus on the histological
      subtypes of hepatoblastoma. SUMMARY: International collaborative efforts in
      hepatoblastoma have led to a new international histopathologic consensus
      classification, refinements in risk stratification, advances in chemotherapy, and
      a better understanding of surgical resection options forming the foundation for
      the development of an upcoming international therapeutic trial.

PMID- 24322719
TI  - Proton beam therapy: a fad or a new standard of care.
AB  - PURPOSE OF REVIEW: Newer methods and advances in radiation therapy promise to
      reduce the risk of complications in children who require irradiation. They have
      secured the role of radiation therapy in the treatment of a variety of pediatric
      central nervous system and solid tumors and for young patients enrolled on
      clinical trials. RECENT FINDINGS: Proton therapy is the latest advancement in
      radiation therapy. Its availability is increasing as new centers are built
      throughout the United States. Pediatric specialists should understand that proton
      therapy is in its pioneering stage of development and that advantages have not
      been quantitatively demonstrated. Proton therapy clearly reduces collateral
      radiation dose to normal tissue when compared with photon (X-ray)-based methods
      of irradiation and has the potential to selectively and safely escalate dose to
      high-risk tumors; however, research results are lacking in both of these areas,
      leading to some confusion among pediatric specialists with regard to indications
      and the need to refer patients for this limited resource and expensive form of
      radiation therapy. SUMMARY: This review highlights a number of issues surrounding
      proton therapy in children and supports the use of proton therapy in clinical
      trials.

PMID- 24322720
TI  - The role of protein characteristics in the formation and fluorescence of Au
      nanoclusters.
AB  - Protein-encapsulated gold nanoclusters have shown many advantages over other gold
      nanocluster systems, including green synthesis, biocompatibility, high water
      solubility, and the ease of further conjugation. In this article, we
      systematically investigated the effects of the protein size and amino acid
      content on the formation and fluorescent properties of gold nanoclusters using
      four model proteins (bovine serum albumin, lysozyme, trypsin, and pepsin). We
      discovered that the balance of amine and tyrosine/tryptophan containing residues
      was critical for the nanocluster formation. Protein templates with low cysteine
      contents caused blue shifts in the fluorescent emissions and difference in
      fluorescent lifetimes of the gold nanoclusters. Furthermore, the protein size was
      found to be a critical factor for the photostability and long-term stability of
      gold nanoclusters. The size of the protein also affected the Au nanocluster
      behaviour after immobilization. 

PMID- 24322721
TI  - The influenza epidemic of 1889-90 in selected European cities--a picture based on
      the reports of two Poznan daily newspapers from the second half of the nineteenth
      century.
AB  - The largest nineteenth-century epidemic of influenza, called 'the Russian
      epidemic,' arrived in Europe from the east in November and December of 1889. It
      was one of the first epidemics of influenza that occurred during the period of
      the rapid development of bacteriology. It was the first epidemic to be so widely
      commented on in the intensively developing daily press. Daily Polish newspapers
      published in Poznan, a Polish city that was then under Prussian rule, also had a
      share in providing information on the epidemic. Press reports not only referred
      to the local spread of the disease, but also discussed the situation in numerous,
      often distant, European cities, such as Paris, London, Vienna, and Berlin. Apart
      from data about where and when the illness occurred, the reports provided:
      descriptions of symptoms, treatment methods, data on morbidity and mortality,
      effect on individual people of high rank in the country, information on the
      activities of public authorities, and impact of the epidemic on daily life. The
      1889-1890 influenza epidemic had 2 faces: the real one, discovered while being
      afflicted with the disease, and the media one, discovered through the information
      available in the press. 

PMID- 24322724
TI  - Disease genetics: phenome-wide association studies go large.

PMID- 24322729
TI  - Stem cells: Competitive behaviour of cancer mutations.

PMID- 24322726
TI  - The role of replicates for error mitigation in next-generation sequencing.
AB  - Advances in next-generation sequencing (NGS) technologies have rapidly improved
      sequencing fidelity and substantially decreased sequencing error rates. However,
      given that there are billions of nucleotides in a human genome, even low
      experimental error rates yield many errors in variant calls. Erroneous variants
      can mimic true somatic and rare variants, thus requiring costly confirmatory
      experiments to minimize the number of false positives. Here, we discuss sources
      of experimental errors in NGS and how replicates can be used to abate such
      errors.

PMID- 24322733
TI  - Infrared and reflectron time-of-flight mass spectroscopic analysis of methane
      (CH4)-carbon monoxide (CO) ices exposed to ionization radiation--toward the
      formation of carbonyl-bearing molecules in extraterrestrial ices.
AB  - Ice mixtures of methane and carbon monoxide were exposed to ionizing radiation in
      the form of energetic electrons at 5.5 K to investigate the formation of carbonyl
      bearing molecules in extraterrestrial ices. The radiation induced chemical
      processing of the mixed ices along with their isotopically labeled counterparts
      was probed online and in situ via infrared spectroscopy (solid state) aided with
      reflectron time-of-flight mass spectrometry (ReTOFMS) coupled to single photon
      photoionization (PI) at 10.49 eV (gas phase). Deconvolution of the carbonyl
      absorption feature centered at 1727 cm(-1) in the processed ices and subsequent
      kinetic fitting to the temporal growth of the newly formed species suggests the
      formation of acetaldehyde (CH3CHO) together with four key classes of carbonyl
      bearing molecules: (i) alkyl aldehydes, (ii) alkyl ketones, (iii) alpha,beta
      unsaturated ketones/aldehydes and (iv) alpha,beta,gamma,delta-unsaturated
      ketones/alpha,beta-dicarbonyl compounds in keto-enol form. The mechanistical
      studies indicate that acetaldehyde acts as the key building block of higher
      aldehydes (i) and ketones (ii) with unsaturated ketones/aldehydes (iii) and/or
      alpha,beta-dicarbonyl compounds (iv) formed from the latter. Upon sublimation of
      the newly synthesized molecules, ReTOFMS together with isotopic shifts of the
      mass-to-charge ratios was exploited to identify eleven product classes containing
      molecules with up to six carbon atoms, which can be formally derived from C1-C5
      hydrocarbons incorporating up to three carbon monoxide building blocks. The
      classes are (i) saturated aldehydes/ketones, (ii) unsaturated aldehydes/ketones,
      (iii) doubly unsaturated aldehydes/ketones, (iv) saturated dicarbonyls
      (aldehydes/ketones), (v) unsaturated dicarbonyls (aldehydes/ketones), (vi)
      saturated tricarbonyls (aldehydes/ketones), molecules containing (vii) one
      carbonyl - one alcohol (viii), two carbonyls - one alcohol, (ix) one carbonyl -
      two alcohol groups along with (x) alcohols and (xi) diols. Reaction pathways to
      synthesize these classes were derived as well. The present experiments provide
      clear evidence for the formation of key organic molecules--acetaldehyde, acetone,
      and potentially vinylalcohol--which are among the 15 carbonyl containing organic
      molecules detected in the interstellar medium. Despite numerous previous
      experimental investigations probing the effect of ionizing radiation on simple
      astrophysical ice representatives, our results suggest that more complex organic
      molecules can be formed in extraterrestrial ices than previously suggested. An
      outlook on further identification of individual isomers is also presented.

PMID- 24322734
TI  - Profile: Sinovac.

PMID- 24322735
TI  - Approaches for the analysis of low molecular weight compounds with laser
      desorption/ionization techniques and mass spectrometry.
AB  - This review summarizes various approaches for the analysis of low molecular
      weight (LMW) compounds by different laser desorption/ionization mass spectrometry
      techniques (LDI-MS). It is common to use an agent to assist the ionization, and
      small molecules are normally difficult to analyze by, e.g., matrix assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) using the common matrices
      available today, because the latter are generally small organic compounds
      themselves. This often results in severe suppression of analyte peaks, or
      interference of the matrix and analyte signals in the low mass region. However,
      intrinsic properties of several LDI techniques such as high sensitivity, low
      sample consumption, high tolerance towards salts and solid particles, and rapid
      analysis have stimulated scientists to develop methods to circumvent matrix
      related issues in the analysis of LMW molecules. Recent developments within this
      field as well as historical considerations and future prospects are presented in
      this review. 

PMID- 24322736
TI  - Factors associated with lateral pelvic recurrence after curative resection
      following neoadjuvant chemoradiotherapy in rectal cancer patients.
AB  - PURPOSE: This study aims to determine the risk factors for lateral pelvic
      recurrence (LPR) in rectal cancer patients treated with neoadjuvant
      chemoradiotherapy (CRT) and curative surgery. METHODS: Four hundred forty-three
      patients treated with neoadjuvant CRT and curative surgery from October 1999
      through June 2009 were analyzed. All patients underwent total mesorectal
      resection without lateral pelvic lymph node (LPLN) dissection. Recurrence
      patterns and lateral pelvic recurrence-free survival (LPFS) were evaluated
      relative to clinicopathologic parameters including pelvic LN status. RESULTS:
      Median follow-up was 52 months, with locoregional recurrence in 53 patients (11.9
      %). Of the 53 patients, 28 (52.8 %) developed LPR, of which eight had both
      central and lateral PR. Multivariate analysis showed a significant relationship
      between LPFS and the number of lateral pelvic LN (p = 0.010) as well as the ratio
      of the number of positive LN/number of dissected LN (p = 0.038). The relationship
      between LPFS and LPLN size had a marginal trend (p = 0.085). Logistic regression
      analysis showed positive relationships between LPR probability and the number of
      LPLN (odds ratio [OR] 1.507; 95 % confidence interval [CI] 1.177-1.929; p =
      0.001) as well as LPLN size (OR 1.124; CI 1.029-1.227, p = 0.009). CONCLUSIONS:
      LPLN >= 2 and a ratio of the number of positive LN/number of dissected LN > 0.3
      were prognostic of poor LPFS. The prediction curve of LPR according to the number
      and size of LPLN could be useful for determining the benefit of additional
      lateral pelvic treatment.

PMID- 24322737
TI  - Suffering in silence: a community-based study of fecal incontinence in women.
AB  - OBJECTIVE: Fecal incontinence (FI) is a very common problem in women especially
      among the elderly. Women with FI experience significant physical and
      psychological disability and lifestyle limitations. This study attempts to
      estimate FI among community women above 40 years of age and its associated risk
      factors in Tehran, Iran. STUDY DESIGN: In this cross-sectional study, via cluster
      sampling, a total of 800 community middle-aged women were randomly selected and
      interviewed using a questionnaire. RESULTS: Prevalence of FI was 18.4 %. Our
      findings show that FI was associated with UI, osteoarthritis, diabetes mellitus,
      and inflammatory bowel disease. CONCLUSIONS: FI was a prevalent condition in
      Iranian middle-aged women. Future efforts should be aimed at screening FI in
      women, offering services to treat them, reducing personal and complication
      related costs, and improving their quality of life.

PMID- 24322738
TI  - Spontaneous ureterocolic fistula secondary to diverticulitis: report of a case
      and review of literature.

PMID- 24322739
TI  - Two studies on optimal timing for measles vaccination.

PMID- 24322740
TI  - HBV and HCV infection and pancreatic ductal adenocarcinoma.

PMID- 24322741
TI  - Chronic hepatitis virus infection increases the risk of pancreatic cancer: a meta
      analysis.
AB  - BACKGROUND: Several reports have inconsistently demonstrated that there is an
      association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infections
      and pancreatic cancer (PC). The aim of the present meta-analysis is to assess
      this possible relationship. DATA SOURCES: Studies were identified by searching
      available database from January 2000 to July 2012. Possible associations between
      PC risk and hepatitis B surface antigen (HBsAg) and its antibody (HBsAb),
      hepatitis B e antigen (HBeAg) and its antibody (HBeAb), anti-HBcAg antibody
      (HBcAb), and HCV antibody (anti-HCV) were evaluated. RESULTS: Eight case-control
      and two cohort studies were included, and their quality scores were assessed by
      the modified Newcastle-Ottawa Quality Assessment Scale (NOS). We found that HBsAg
      and anti-HCV seropositivity significantly increased risk of PC (OR=1.28, 95% CI:
      1.11-1.48 and OR=1.21, 95% CI: 1.02-1.44). The presence of HBsAb was associated
      with a statistically significant decrease in the risk of PC (OR=0.40, 95% CI:
      0.20-0.79) and HBeAb (OR=0.62, 95% CI: 0.39-0.99). HBsAg-/HBcAb+/HBsAb- or HBsAg
      /HBcAb+/HBsAb+ profile was not related to PC risk (OR=1.57, 95% CI: 0.83-2.98 and
      OR=1.24, 95% CI: 0.72-2.14). CONCLUSIONS: HBV/HCV infection increases the risk of
      PC. HBsAb and HBeAb seropositivity may be the protective factors against PC. It
      is still uncertain whether serological pattern of past exposure to HBV with or
      without natural immunity is associated with an enhanced probability of this
      malignancy.

PMID- 24322742
TI  - Novel anti-diabetic agents in non-alcoholic fatty liver disease: a mini-review.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum that
      ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and to
      cirrhosis. The recommended treatment for this disease includes measures that
      target obesity and insulin resistance. The present review summarizes the role of
      newer anti-diabetic agents in treatment of NAFLD. DATA SOURCES: PubMed, MEDLINE
      and Ovid databases were searched to identify human studies between January 1990
      and January 2013 using specified key words. Original studies that enrolled
      patients with a diagnosis of NAFLD or NASH and involved use of newer classes of
      anti-diabetic agents for a duration of at least 3 months were included. RESULTS:
      Out of the screened articles, four met eligibility criteria and were included in
      our review. The classes of newer anti-diabetic medications described were
      dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 analogues.
      CONCLUSIONS: Liraglutide and Exenatide showed improvement in transaminases as
      well as histology in patients with NASH. Sitagliptin showed improvement in
      transaminases but limited studies are there to access its effect on histology.
      Further studies are needed to support use of newer anti-diabetic medications in
      patients with NAFLD.

PMID- 24322743
TI  - Glasgow coma scale and APACHE-II scores affect the liver transplantation outcomes
      in patients with acute liver failure.
AB  - BACKGROUND: The timing and selection of patients for liver transplantation in
      acute liver failure are great challenges. This study aimed to investigate the
      effect of Glasgow coma scale (GCS) and APACHE-II scores on liver transplantation
      outcomes in patients with acute liver failure. METHOD: A total of 25 patients
      with acute liver failure were retrospectively analyzed according to age,
      etiology, time to transplantation, coma scores, complications and mortality.
      RESULTS: Eighteen patients received transplants from live donors and 7 had
      cadaveric whole liver transplants. The mean duration of follow-up after liver
      transplantation was 39.86+/-40.23 months. Seven patients died within the
      perioperative period and the 1-, 3-, 5-year survival rates of the patients were
      72%, 72% and 60%, respectively. The parameters evaluated for the perioperative
      deaths versus alive were as follows: the mean age of the patients was 33.71 vs 28
      years, MELD score was 40 vs 32.66, GCS was 5.57 vs 10.16, APACHE-II score was 23
      vs 18.11, serum sodium level was 138.57 vs 138.44 mmol/L, mean waiting time
      before the operation was 12 vs 5.16 days. Low GCS, high APACHE-II score and
      longer waiting time before the operation (P<0.01) were found as statistically
      significant factors for perioperative mortality. CONCLUSION: Lower GCS and higher
      APACHE-II scores are related to poor outcomes in patients with acute liver
      failure after liver transplantation.

PMID- 24322744
TI  - Characteristics of alcoholic liver disease and predictive factors for mortality
      of patients with alcoholic cirrhosis.
AB  - BACKGROUND: Alcoholic liver disease is one of the major chronic liver diseases
      worldwide. The aim of the study was to describe the clinical characteristics of
      alcoholic liver disease and to compare the predictive values of biochemical
      parameters, complications, Child-Turcotte-Pugh score, model for end-stage liver
      disease (MELD) score and discriminant function score for the mortality of in
      hospital or 3-month after discharge of patients with alcoholic cirrhosis (AC).
      METHODS: A retrospective record review and statistical analysis were performed on
      205 consecutive patients with the discharge diagnosis of alcoholic liver disease.
      Three models were used to predict the mortality of patients with AC. The number
      of variceal hemorrhage, infection, hepatic encephalopathy and hepatocellular
      carcinoma was analyzed as "numbers of complications". Model 1 consisted of
      creatinine, white blood cell count, international normalized ratio and "numbers
      of complications". Model 2 consisted of MELD score. Model 3 included "numbers of
      complications" and MELD score. RESULTS: The risk of developing AC was significant
      for patients with alcohol consumption of higher than 80 g/d (OR=2.807, P<0.050)
      and drinking duration of longer than 10 years (OR=3.429, P<0.028). The area under
      curve for predicting in-hospital mortality of models 1, 2 and 3 was 0.950, 0.886
      and 0.911 (all P<0.001), respectively. The area under curve for predicting the 3
      month mortality of models 1, 2 and 3 was 0.867, 0.878 and 0.893 (all P<0.001),
      respectively. CONCLUSIONS: There is a dose-dependent relationship between alcohol
      consumption and the risk of developing AC. MELD score has a better predictive
      value than Child-Turcotte-Pugh or discriminant function score for patients with
      AC, and model 1 or 3 is better than model 2.

PMID- 24322745
TI  - Treatment of liver metastases from uveal melanoma: a retrospective single-center
      analysis.
AB  - BACKGROUND: Metastatic liver melanoma is a rare event in the Chinese population
      with extremely poor prognosis. Any treatment that controls a metastatic hepatic
      lesion potentially prolongs survival. This study aimed to evaluate the survival
      of patients with isolated liver metastases from uveal melanoma treated with
      partial hepatectomy or non-surgical management and to find the best therapeutic
      modality for these patients. METHODS: From January 1996 to September 2008, eight
      patients with liver metastases secondary to uveal melanoma were admitted to our
      hospital. Five patients underwent partial hepatectomy and 3 received other
      treatments (TACE, RFA, PEI). Their medical records were reviewed and overall
      survival was analyzed. RESULTS: The patients comprised 3 men and 5 women, with a
      median age of 44 years. Six patients presented with liver metastases at the time
      the primary tumor was diagnosed. The interval from the diagnosis of uveal
      melanoma to liver metastasis in the remaining 2 patients was 9.5 and 32.5 months,
      respectively. The median survival after the treatment of liver metastasis was
      11.5 and 7.5 months in the surgical and non-surgical groups, respectively. There
      was no procedure-related mortality in the whole study cohort. CONCLUSIONS:
      Partial hepatectomy or other therapies were safe and feasible for isolated liver
      metastases from uveal melanoma. Aggressive treatment with multidisciplinary
      modalities may result in prolonged survival.

PMID- 24322746
TI  - Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in
      Chinese patients: a multicenter, open-label, phase III study.
AB  - BACKGROUND: Contrast agents help to improve visibility in magnetic resonance (MR)
      imaging. However, owing to the large interstitial spaces of the liver, there is a
      reduction in the natural contrast gradient between lesions and healthy tissue.
      This study was undertaken to evaluate the efficacy and safety of the liver
      specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese
      patients. METHODS: This was a single-arm, open-label, multicenter study in
      patients with known or suspected focal liver lesions referred for contrast
      enhanced MR imaging. MR imaging was performed in 234 patients before and after a
      single intravenous bolus of Gd-EOB-DTPA (0.025 mmol/kg body weight). Images were
      evaluated by clinical study investigators and three independent, blinded
      radiologists. The primary efficacy endpoint was sensitivity in lesion detection.
      RESULTS: Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46% compared
      with pre-contrast imaging for the average of the three blinded readers (94.78% vs
      85.32% for Gd-EOB-DTPA vs pre-contrast, respectively). Improvements in detection
      were more pronounced in lesions less than 1 cm. Gd-EOB-DTPA improved diagnostic
      accuracy in lesion classification. CONCLUSIONS: This open-label study
      demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,
      particularly in those smaller than 1 cm. Gd-EOB-DTPA also significantly improves
      the diagnostic accuracy in lesion classification, and furthermore, Gd-EOB-DTPA is
      safe in Chinese patients with liver lesions.

PMID- 24322747
TI  - CT assessment of liver hemodynamics in patients with hepatocellular carcinoma
      after argon-helium cryoablation.
AB  - BACKGROUND: Assessment of tumor response after argon-helium cryoablation is
      critical in guiding future therapy for unresectable hepatocellular carcinoma.
      This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after
      argon-helium cryoablation with computed tomography perfusion. METHODS: The
      control group comprised 40 volunteers without liver disease. The experimental
      group was composed of 15 patients with hepatocellular carcinoma treated with
      argon-helium cryoablation. Computed tomography perfusion parameters were
      measured: hepatic blood flow, hepatic blood volume, mean transit time,
      permeability of capillary vessel surface, hepatic arterial fraction, hepatic
      arterial perfusion, and hepatic portal perfusion. RESULTS: After treatment, in
      the tumor foci, permeability of capillary vessel surface was higher, and hepatic
      blood flow, hepatic blood volume, hepatic arterial fraction, and hepatic arterial
      perfusion values were lower (P<0.05). In the liver parenchyma surrounding the
      tumor, hepatic arterial perfusion was significantly lower (P<0.05); however,
      there was no significant difference in hepatic blood flow, hepatic blood volume,
      mean transit time, permeability of capillary vessel surface, hepatic arterial
      fraction, or hepatic portal perfusion (P>0.05). CONCLUSION: Computed tomography
      perfusion can evaluate tumor response after argon-helium cryoablation.

PMID- 24322748
TI  - Effect of hepatic artery embolization on liver hypertrophy response in a rabbit
      liver VX2 tumor model.
AB  - BACKGROUND: Portal vein embolization not only induces hypertrophy of the non
      embolized liver, but also enhances tumor growth. The latter could be prevented by
      embolizing the hepatic arteries supplying the tumor-bearing liver segments. This
      study aimed to determine the effects of transcatheter arterial embolization (TAE)
      on tumor volume and liver regeneration in a rabbit VX2 tumor model. METHODS:
      Twenty-three rabbits underwent subcapsular tumor implantation with a VX2 tumor.
      Two weeks after implantation, 18 rabbits were used for TAE experiments, 5 were
      for sham controls. Tumor response and liver regeneration response of the
      embolized cranial and non-embolized caudal liver lobes were assessed by CT
      volumetry, liver to body weight index, and the amount of proliferating
      hepatocytes. RESULTS: All super-selective arterial tumor embolization procedures
      were performed successfully. Despite embolization, the tumor volume increased
      after an initial steady state. The tumor volume after embolization was smaller
      than that of the sham group, but this difference was not significant. Massive
      necrosis of the tumor, however, was seen after embolization, without damage of
      the surrounding liver parenchyma. There was a significant atrophy response of the
      tumor bearing cranial lobe after super-selective arterial embolization of the
      tumor with a concomitant hypertrophy response of the non-embolized, caudal lobe.
      This regeneration response was confirmed histologically by a significantly higher
      number of proliferating hepatocytes on the Ki-67 stained slides. CONCLUSIONS:
      Super-selective, bland arterial coil embolization causes massive necrosis of the
      tumor, despite increase of volume on CT scan. Atrophy of the tumor bearing liver
      lobe is seen after arterial embolization of the tumor with a concomitant
      hypertrophy response of the non-embolized lobe, despite absence of histological
      damage of the tumor-surrounding liver parenchyma.

PMID- 24322749
TI  - Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver
      disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent
      causes of liver diseases, with markedly increased prevalence. However, its
      mechanisms are not clear. The present study was undertaken to illustrate the role
      of caveolin-1 (cav1) and the scavenger receptor class B type 1 (SR-B1) in NAFLD.
      METHODS: Adult male C57BL/6 mice were fed with a normal diet or high fat and
      cholesterol (HFC) diet for 14 weeks. The mice were sacrificed to collect plasma
      and harvest the liver; their plasma lipid concentration was measured. Hepatic
      cav1 and SR-B1 mRNA and protein expression were determined by real-time
      quantitative polymerase chain reaction (qPCR) and Western blotting, respectively.
      In order to study cav1 and SR-B1 distribution and change in hepatocytes,
      immunohistochemical analysis was performed. RESULTS: HFC diet increased plasma
      lipids, induced NAFLD and increased the liver/body weight ratio. Compared to the
      control mice (n=6), the mRNA and protein levels of cav1 and SR-B1 in liver tissue
      of the NAFLD mice (n=12) increased significantly (cav1 mRNA: 1.536+/-0.226 vs
      0.980+/-0.272, P<0.05; protein: 0.643+/-0.240 vs 0.100+/-0.130, P<0.01; SR-B1
      mRNA: 1.377+/-0.125 vs 0.956+/-0.151, P<0.01; protein: 2.156+/-0.507 vs 0.211+/
      0.211, P<0.01). Furthermore, both cav1 and SR-B1 immunoreactivity increased and
      their distribution was also changed, mainly in the plasma membrane of
      hepatocytes, cytoplasm and membrane of lipid droplets and around. CONCLUSION:
      NAFLD is associated with increased concentration of plasma lipids and
      upregulation of hepatic cav1 and SR-B1 gene and protein expressions, which
      indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of
      NAFLD.

PMID- 24322750
TI  - Frey procedure for the treatment of chronic pancreatitis associated with common
      bile duct stricture.
AB  - BACKGROUND: The Frey procedure (FP) is the treatment of choice for symptomatic
      chronic pancreatitis (CP). In cases of biliary stricture, biliary derivation can
      be performed by choledochoduodenostomy, Roux-en-Y choledochojejunostomy or, more
      recently, reinsertion of the common bile duct (CBD) into the resection cavity.
      The objective of the present study was to evaluate the outcomes associated with
      each of these three types of biliary derivation. METHODS: We retrospectively
      analyzed demographic, CP-related, surgical and follow-up data for patients having
      undergone FP for CP with biliary derivation between 2004 and 2012 in our
      university medical center. The primary efficacy endpoint was the rate of CBD
      stricture recurrence. The secondary endpoints were surgical parameters,
      postoperative complications, postoperative follow-up and the presence of risk
      factors for secondary CBD stricture. RESULTS: Eighty patients underwent surgery
      for CP during the study period. Of these, 15 patients received biliary derivation
      with the FP. Eight of the FPs (53.3%) were combined with choledochoduodenostomy,
      4 (26.7%) with choledochojejunostomy and 3 (20.0%) with reinsertion of the CBD
      into the resection cavity. The mean operating time was 390 minutes. Eleven
      complications (73.3%) were recorded, including one major complication (6.7%) that
      necessitated radiologically-guided drainage of an abdominal collection. The mean
      (range) length of stay was 17 days (8-28) and the median (range) follow-up time
      was 35.2 months (7.2-95.4). Two patients presented stricture after CBD
      reinsertion into the resection cavity; one was treated with radiologically-guided
      dilatation and the other underwent revisional Roux-en-Y choledochojejunostomy.
      Three patients presented alkaline reflux gastritis (37.5%), one (12.5%)
      cholangitis and one CBD stricture after FP with choledochoduodenostomy. No risk
      factors for secondary CBD stricture were identified. CONCLUSIONS: As part of a
      biliary derivation, the FP gave good results. We did not observe any
      complications specifically related to surgical treatment of the biliary tract.
      However, CBD reinsertion into the resection cavity appeared to be associated with
      a higher stricture recurrence rate. In our experience, choledochojejunostomy
      remains the "gold standard" for the surgical treatment for CBD strictures.

PMID- 24322751
TI  - Bedside index for severity in acute pancreatitis: comparison with other scoring
      systems in predicting severity and organ failure.
AB  - BACKGROUND: The early identification of severe acute pancreatitis is important
      for the management and for improving outcomes. The bedside index for severity in
      acute pancreatitis (BISAP) has been considered as an accurate method for risk
      stratification in patients with acute pancreatitis. This study aimed to evaluate
      the comparative usefulness of the BISAP. METHODS: We retrospectively analyzed 303
      patients with acute pancreatitis diagnosed at our hospital from March 2007 to
      December 2010. BISAP, APACHE-II, Ranson criteria, and CT severity index (CTSI) of
      all patients were calculated. We stratified the number of patiants with severe
      pancreatitis, pancreatic necrosis, and organ failure as well as the number of
      deaths by BISAP score. We used the area under the receiver-operating curve (AUC)
      to compare BISAP with other scoring systems, C-reactive protein (CRP),
      hematocrit, and body mass index (BMI) with regard to prediction of severe acute
      pancreatitis, necrosis, organ failure, and death. RESULTS: Of the 303 patiants,
      31 (10.2%) were classified as having severe acute pancreatitis. Organ failure
      occurred in 23 (7.6%) patients, pancreatic necrosis in 40 (13.2%), and death in 6
      (2.0%). A BISAP score of 2 was a statistically significant cutoff value for the
      diagnosis of severe acute pancreatitis, organ failure, and mortality. AUCs for
      BISAP predicting severe pancreatitis and death were 0.80 and 0.86, respectively,
      which were similar to those for APACHE-II (0.80, 0.87) and Ranson criteria (0.74,
      0.74) and greater than AUCs for CTSI (0.67, 0.42). The AUC for organ failure
      predicted by BISAP, APACHE-II, Ranson criteria, and CTSI was 0.93, 0.95, 0.84 and
      0.57, respectively. AUCs for BISAP predicting severity, organ failure, and death
      were greater than those for CRP (0.69, 0.80, 0.72), hematocrit (0.45, 0.35,
      0.14), and BMI (0.41, 0.47, 0.17). CONCLUSION: The BISAP predicts severity,
      death, and especially organ failure in acute pancreatitis as well as APACHE-II
      does and better than Ranson criteria, CTSI, CRP, hematocrit, and BMI.

PMID- 24322753
TI  - Indocyanine green clearance in evaluating the recovery of liver reserve function
      after superselective transarterial chemoembolization.
AB  - Transarterial chemoembolization (TACE) may ravage normal liver tissues apart from
      the neoplastic nodules which offset the anti-tumor effect. This study aimed to
      evaluate the recovery of liver reserve function (LRF) after TACE by indocyanine
      green (ICG) clearance test and other routine liver function tests. Forty-six
      newly diagnosed HCC patients who had undergone TACE as the initial treatment from
      January 2011 to January 2012 were enrolled in this study. The effects of age,
      basic ICG clearance rate and interval time between two assessments on the
      recovery of LRF were analyzed. We found that ICG retention rate at the 15 minutes
      (ICGR15) was significantly increased after TACE (12.3+/-8.1% vs 16.8+/-12.1%,
      P<0.01) in all the 46 patients. In particular, the ICGR15 value was increased in
      older patients (age>55 years, 20.3+/-12.5% vs 13.7+/-7.2%, P<0.01). The interval
      of ICG test also affected the ICGR15 value (<=47 days, 17.8+/-11.4% after vs
      12.1+/-7.1% before TACE, P<0.01). Our data suggested that TACE decreased LRF,
      especially in older patients. ICG test was more sensitive to evaluate the
      recovery of LRF after TACE than the Child-Pugh grade and routine liver function
      tests. 

PMID- 24322752
TI  - Ligamentum teres hepatis patch enhances the healing of pancreatic fistula after
      distal pancreatectomy.
AB  - Pancreatic fistula is one of the most common complications after the distal
      pancreatectomy. Many methods have been tried to solve the problem, but no one is
      optimal, especially for the soft pancreatic stump cases. This study used
      ligamentum teres hepatis as a patch to cover the pancreatic stump. Between
      October 2010 and December 2012, seventy-seven patients who had undergone distal
      pancreatectomy with a soft pancreatic stump were divided into two groups: group A
      (n=39, patients received conventional ligated main pancreatic duct method) and
      group B (n=38, patients underwent a coverage procedure). Patients in group A had
      a longer recovery from postoperative pancreatic fistula than those in group B
      (16.4+/-3.5 vs 10.8+/-1.6 days, P<0.05). The coverage procedure with ligamentum
      teres hepatis is a safe, effective and convenient method for patients with a soft
      pancreas remnant during distal pancreatectomy. 

PMID- 24322754
TI  - MicroRNA-216a: a potential therapeutic target for drug resistance and recurrent
      of liver cancer.

PMID- 24322755
TI  - BIX-01294 induces autophagy-associated cell death via EHMT2/G9a dysfunction and
      intracellular reactive oxygen species production.
AB  - We screened a chemical library in MCF-7 cells stably expressing green fluorescent
      protein (GFP)-conjugated microtubule-associated protein 1 light chain 3 (LC3)
      (GFP-LC3-MCF-7) using cell-based assay, and identified BIX-01294 (BIX), a
      selective inhibitor of euchromatic histone-lysine N-methyltransferase 2 (EHMT2),
      as a strong autophagy inducer. BIX enhanced formation of GFP-LC3 puncta, LC3-II,
      and free GFP, signifying autophagic activation. Inhibition of these phenomena
      with chloroquine and increasement in punctate dKeima ratio (550/438) signal
      indicated that BIX activated autophagic flux. BIX-induced cell death was
      suppressed by the autophagy inhibitor, 3-methyladenine, or siRNA against BECN1
      (VPS30/ATG6), ATG5, and ATG7, but not by caspase inhibitors. Moreover, EHMT2
      siRNA augmented GFP-LC3 puncta, LC3-II, free GFP, and cell death, implying that
      inhibition of EHMT2 caused autophagy-mediated cell death. Treatment with EHMT2
      siRNA and BIX accumulated intracellular reactive oxygen species (ROS). BIX
      augmented mitochondrial superoxide via NADPH oxidase activation. In addition, BIX
      increased hydrogen peroxide and glutathione redox potential in both cytosol and
      mitochondria. Treatment with N-acetyl-L-cysteine (NAC) or diphenyleneiodonium
      chloride (DPI) decreased BIX-induced LC3-II, GFP-LC3 puncta, and cell death,
      indicating that ROS instigated autophagy-dependent cell death triggered by BIX.
      We observed that BIX potentiated autophagy-dependent and caspase-independent cell
      death in estrogen receptor (ESR)-negative SKBr3 and ESR-positive MCF-7 breast
      cancer cells, HCT116 colon cancer cells, and importantly, in primary human breast
      and colon cancer cells. Together, the results suggest that BIX induces autophagy
      dependent cell death via EHMT2 dysfunction and intracellular ROS accumulation in
      breast and colon cancer cells, therefore EHMT2 inhibition can be an effective
      therapeutic strategy for cancer treatment. 

PMID- 24322756
TI  - Synthesis, spectroscopic, X-ray crystal structure, biological and DNA interaction
      studies of organotin(IV) complexes of 2-(4-ethoxybenzylidene) butanoic acid.
AB  - Six organotin(IV) carboxylates of the type R2SnL2 [R=CH3 (1), n-C4H9 (2), n-C8H17
      (3)] and R3SnL [R=CH3 (4), n-C4H9 (5), C6H5 (6), where L=2-(4-ethoxybenzylidene)
      butanoic acid, have been synthesized and characterized by elemental analysis, FT
      IR and NMR ((1)H, (13)C). The complex (1) was also analyzed by single crystal X
      ray analysis. The complexes were screened for antimicrobial, cytotoxic and anti
      tumor activities. The results showed significant activity in each area of the
      activity with few exceptions. DNA interactions studies of ligand HL and
      representative complex 2 were investigated by UV-Visible absorption spectroscopy
      and viscosity measurements. The results showed that both ligand HL and complex 2
      interact with SS-DNA via intercalation as well as minor groove binding.

PMID- 24322757
TI  - Surface enhanced Raman scattering (SERS) spectra of trinitrotoluene in silver
      colloids prepared by microwave heating method.
AB  - Surface enhanced Raman spectroscopy (SERS) has been demonstrated for the
      detection of trace levels of explosives due to its high sensitivity, speed of
      detection and fingerprint feature. 2,4,6-Trinitrotoluene (TNT), a leading example
      of nitroaromatic explosives, is causing wide concern. In this study, SERS spectra
      of TNT solution in silver colloids have been successfully measured and a
      comparison was drawn with the normal Raman spectra of bulk TNT. The silver
      colloids were prepared by the microwave heating method and characterized by UV
      Vis spectra and the scanning electron microscopy (SEM). NaCl and pH value have a
      great impact on SERS intensity of TNT, the corresponding experimental research
      results and theoretical interpretations were further illustrated to a certain
      extent. Moreover, the detection limit of TNT in aqueous solution was achieved as
      low as 10(-10) mol L(-1) and some preliminary experiments of detecting TNT vapor
      (about 10 MUg/L) using SERS have been carried out. Our results demonstrated the
      potential of SERS for probing TNT with high sensitivity, and suggest SERS as a
      powerful method for detection of TNT and similar species at trace levels.

PMID- 24322758
TI  - Colorimetric chemosensor for multi-signaling detection of metal ions using
      pyrrole based Schiff bases.
AB  - Pyrrole based Schiff bases act as a highly sensitive probe for metal ions in
      aqueous medium. Both receptors R1 and R2 are sensitive towards Fe(3+), Cu(2+),
      Hg(2+) and Cr(3+) among the other metal ions. The sensing ability of the
      receptors are investigated via colorimetric, optical and emission spectroscopic
      studies. The binding stoichiometries of R1 and R2 with metal ions have been
      determined as 2:1 by using Job's plot. The colorimetric receptors exhibited high
      sensitivity with a low detection limit of MUM levels. In the presence of metal
      ions both receptors shows fluorescence quenching. This might be due to the photo
      induced electron transfer mechanism. The quenching constant was further
      determined using Stern-Volmer plot. 

PMID- 24322759
TI  - Synthesis, growth, spectral, and thermal studies of a new organic molecular
      charge transfer complex crystal: 3-nitroaniline 4-methyl benzene sulfonate.
AB  - A new organic intermolecular charge transfer complex 3-nitroaniline 4-methyl
      benzene sulfonate (NATS) has been successfully synthesized and good optical
      quality single crystals grown by slow solvent evaporation solution growth
      technique at room temperature using methanol as the solvent. The (1)H and (13)C
      NMR spectra were recorded to establish the molecular structure of the title
      complex. The crystal structure of NATS has been determined by single crystal XRD
      analysis and it belongs to orthorhombic crystal system with space group Pbca.
      Fourier transform infrared (FT-IR) spectral study has been carried out to confirm
      the presence of various functional groups present in the complex. Electronic
      absorption spectrum was recorded to find the prevalent charge transfer activity
      in the complex. The UV-Vis-NIR transmission spectrum was recorded in the range
      200-2500 nm, to find the optical transmittance window and lower cut off
      wavelength of the title crystal. The thermal stability of the title complex
      crystal was studied by using thermo-gravimetric and differential thermal analyses
      and found that the compound is stable up to 215  degrees C.

PMID- 24322760
TI  - Streptavidin sensor and its sensing mechanism based on water-soluble fluorescence
      conjugated polymer.
AB  - Fluorescence quenching effect of water-soluble anionic conjugated polymer (CP)
      (poly[5-methoxy-2-(3-sulfopoxy)-1,4-phenylenevinylene] (MPS-PPV)) by [Re(N
      N)(CO)3(py-CH2-NH-biotin)](PF6) [N-N=2,9-dimethyl-4,7-diphenyl-1,10
      phenanthroline; py-CH2-NH-biotin=N-[(4-pyridyl) methyl] biotinamide] (Re-Biotin)
      and fluorescence recovery in the presence of streptavidin (or avidin) were
      investigated using Re-Biotin as quencher tether ligand (QTL) probe. Meanwhile,
      the mechanisms of fluorescence quenching and recovery were discussed to provide
      new thoughts to design biosensor based on water-soluble CPs. The results indicate
      that the sensing mechanisms of streptavidin sensor or avidin sensor, using Re
      Biotin as QTL probe, are the same and stable, whether in non-buffer system
      (aqueous solution) or different buffer systems [0.01 mol.L(-1) phosphate buffered
      solution (pH=7.4), 0.1 mol.L(-1) ammonium carbonate buffered solution (pH=8.9)].
      There exists specific interactions between streptavidin (or avidin) and biotin of
      Re-Biotin. Fluorescence quenching and recovery processes of MPS-PPV are
      reversible. Mechanisms of Re-Biotin quenching MPS-PPV fluorescence can be
      interpreted as strong electrostatic interactions and charge transferences between
      Re-Biotin and MPS-PPV. Fluorescence recovery mechanisms of Re-Biotin-MPS-PPV
      system can be interpreted as specific interactions between streptavidin (or
      avidin) and biotin of Re-Biotin making Re-Biotin far away from MPS-PPV. Avidin or
      strptavidin as re-Biotin probe can not only be quantitatively determinated, but
      also be identified.

PMID- 24322761
TI  - Molecular recognition study of Carbamazepine, antiseizure drug, by p-t-butyl
      calix(8)arene.
AB  - The formation of inclusion complex of Carbamazepine, a antiseizure drug molecule,
      with the supra molecule, p-t-butyl calix(8)arene was studied. p-t-Butyl
      calix(8)arene was the host molecule and Carbamazepine was the guest molecule.
      Optical absorption spectral studies were carried out to study the molecular
      recognition properties of p-t-butyl calix(8)arene with Carbamazepine. The
      stochiometry of the host-guest complex and the binding constant were determined. 

PMID- 24322762
TI  - The use of imidazolium ionic liquid/copper complex as novel and green catalyst
      for chemiluminescent detection of folic acid by Mn-doped ZnS nanocrystals.
AB  - A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum
      dots (QDs) as CL emitter is proposed for the chemiluminometric determination of
      folic acid in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were
      synthesized by using L-cysteine as stabilizer in aqueous solutions. The
      nanoparticles were structurally and optically characterized by X-ray powder
      diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared
      spectroscopy (FTIR), UV-Vis absorption spectroscopy and photoluminescence (PL)
      emission spectroscopy. The CL of ZnS QDs induced by directly chemical oxidation
      and its ionic liquid-sensitized effect in aqueous solution were then
      investigated. It was found that oxidants, especially hydrogen peroxide, could
      directly oxidize ZnS QDs to produce weak CL emission in basic conditions. In the
      presence of 1,3-dipropylimidazolium bromide/copper a drastic light emission
      enhancement is observed, related to a strong interaction between Cu(2+) and the
      imidazolium ring. Therefore, a new CL analysis system was developed for the
      determination of folic acid. Under the optimum conditions, there is a good linear
      relationship between the relative CL intensity and the concentration of folic
      acid in the range of 1*10(-9)-1*10(-)(6) M of folic acid with a correlation
      coefficient (R(2)) of 0.9991. The limit of detection of this system was found to
      be 1*10(-)(10) M. This method is not only simple, sensitive and low cost, but
      also reliable for practical applications.

PMID- 24322763
TI  - Combining continuing education with expert consultation via telemedicine in
      Cambodia.
AB  - Telemedicine has the potential to increase access to both clinical consultation
      and continuing medical education in Cambodia. We present a Cambodian surgical
      centre's experience with a collaboration in which complicated orthopaedic cases
      were presented to a panel of consultants using free online videoconferencing
      software, providing a combined opportunity for both continuing education and the
      enhancement of patient care. Effects of the case conference on patient care were
      examined via a retrospective review and clinician perspectives were elicited via
      a qualitative survey. The case conference altered patient care in 69% of cases.
      All Cambodian staff reported learning from the conference and 78% reported
      changes in their care for patients not presented at the conference. Real-time
      videoconferencing between consultants in the developed world and physicians in a
      developing country may be an effective, low-cost and easily replicable means of
      combining direct benefits to patient care with continuing medical education. 

PMID- 24322764
TI  - Incidence of surgically drained cutaneous abscess in relation to climate in
      Mayotte, Comoros.
AB  - Although skin infections are common in tropical countries, there is scant data
      quantifying the relationship with climate conditions. The aim of this study was
      to assess the incidence and seasonality of skin abscess in Mayotte, Comoros. We
      collected data on patients with cutaneous abscesses requiring surgical drainage
      from January 2009 to December 2010. A total of 3423 abscesses were recorded. The
      overall annualized incidence was 785 cases per 100,000 population (95% confidence
      interval 754-814). The incidence rate peaked in children and abscesses were
      highest during the rainy season (964 cases per 100,000 population per 6 months).
      A greater frequency of insects bites, a lower level of sensitization and lack of
      access to adequate hygiene are potential explanations for these findings. A
      community-based intervention strategy should target vulnerable children in order
      to combat this disease. 

PMID- 24322765
TI  - Cloning and characterization of a protein elicitor Sm1 gene from Trichoderma
      harzianum.
AB  - A small protein, cysteine-rich, designated SM1, produced by Trichoderma virens
      and Trichoderma atroviride, acts as elicitor for triggering plant defense
      reactions. We analyzed Sm1 gene expression of eight different strains of
      Trichoderma spp. grown on glucose, seeds or roots of beans. Regardless of the
      carbon source, T37 strain had significantly higher Sm1 expression and was chosen
      for further studies. When grown on different carbon sources, Sm1 expression was
      highest on galactose, bean seed, glucose and starch. Sm1 gene from T37 strain was
      cloned; it had a single exon, and encoded a protein of 138 amino acids, showing
      high sequence identity with some proteins belonging to the cerato-platanin
      family.

PMID- 24322766
TI  - Optimized expression in Pichia pastoris eliminates common protein contaminants
      from subsequent His-tag purification.
AB  - A weakness of using immobilized metal affinity chromatography (IMAC) to purify
      recombinant proteins expressed in Pichia pastoris is the co-purification of
      native proteins that exhibit high affinities for Ni-IMAC. We have determined the
      elution profiles of P. pastoris proteins and have examined the native proteins
      that co-purify when eluting with 100 mM imidazole. Four major contaminants were
      identified: mitochondrial alcohol dehydrogenase isozyme III (mADH), nucleotide
      excision repair endonuclease, and the hypothetical proteins TPHA_0L01390 and
      TDEL_0B02190 which are homologous proteins derived from Tetrapisispora phaffii
      and Torulaspora delbrueckii, respectively. A new P. pastoris expression strain
      was engineered that eliminated the predominant contaminant, mADH, by gene
      disruption. The total amount of protein contaminants was reduced by 55 % without
      effecting cell growth. The present study demonstrates the feasibility of using a
      proteomic approach to facilitate bioprocess optimization.

PMID- 24322767
TI  - Glycoconjugates synthesized via transglycosylation by a thermostable alpha
      glucosidase from Thermoplasma acidophilum and its glycosynthase mutant.
AB  - A new method is presented for synthesizing arbutin glycosides using alpha
      glucosidase (AglA) from Thermoplasma acidophilum and its glycosynthase mutant. An
      alpha-glycosynthase was constructed by substituting the catalytic nucleophile
      with the non-nucleophile glycine. Enzyme activity was then recovered using an
      external nucleophile. The transglycosylation reaction of AglA using maltose as a
      donor and arbutin as an acceptor produced arbutin coupled with a glucose moiety.
      The products were isolated and further analysed using preparative recycling HPLC.
      Arbutin glycosides linked to C-3, C-4, and C-6 were identified using NMR. The
      transglycosylation products of AglA were used as substrates for the enzyme
      reaction, which were hydrolyzed back again and reduced final yields. The
      glycosynthase mutant produced one main arbutin glycoside linked to C-4 with a
      yield of 38 % without further observed hydrolysis.

PMID- 24322768
TI  - Recombinant expression and characterization of an acid-, alkali- and salt
      tolerant beta-1,3-1,4-glucanase from Paenibacillus sp. S09.
AB  - A new beta-1,3-1,4-glucanase gene (PlicA) was cloned from Paenibacillus sp. S09.
      The ORF contained 717 bp coding for a 238 amino acid protein. PlicA, expressed in
      Escherichia coli and purified by Ni(2+)-affinity chromatography, had optimum
      activity at 55  degrees C and pH 6.2. The specific activity toward barley beta
      glucan reached 7,055 U/mg. K m and V max values with barley beta-glucan were 3.7
      mg/ml and 3.3 * 10(3) MUmol/min mg, respectively. The enzyme exhibited acid- and
      alkali-tolerance with more than 80 % activity remaining after incubation for 4 h
      at pH 3.5-12. PlicA was salt-tolerant (>90 % activity retained in 4 M NaCl at 25 
      degrees C for 24 h) and salt-activated: activity rising 1.5-fold in 0.5 M NaCl.
      The thermostability was improved by NaCl and CaCl2. This is the first report of
      an acid-, alkali- and salt-tolerant bacterial beta-1,3-1,4-glucanase with high
      catalytic efficiency.

PMID- 24322769
TI  - Modification to the injection needle to a screw needle improves effective cell
      delivery in acute myocardial infarction.
AB  - Evaluation of therapeutic effects of transplanted cells in ischemic heart failure
      models are important issues. However, traditional injection needles that are
      widely used in clinical practice tend to reduce the amount of functional cells
      relative to the injected amount. We now describe a cell transplantation technique
      using a screw needle. After inducing acute myocardial infarction in a rat model,
      human embryonic stem cell-derived endothelial cells were injected into the
      infarcted regions with a screw or straight-curved needle. When an equal volume of
      cells was transplanted, the screw group suffered minimal cell loss, showed
      improvement in LV wall thickness (74.5 +/- 6.2 vs. 64.4 +/- 7.8 %), epicardium
      scar length (19.3 +/- 2.8 vs. 24.6 +/- 6.4 %), and area of engraft. Thus, even a
      simple change in the structure of an instrument can have a large impact on
      transplantation efficiency.

PMID- 24322770
TI  - Molecular cloning and characterization of the alpha-chain gene of goose
      immunoglobulin heavy chain.
AB  - A novel gene encoding the alpha-chain of goose immunoglobulin heavy-chain
      (Igalpha) was cloned by reverse transcription-PCR. The cDNA had 1,760 bp and
      encompassed a partial V-D-J region of the heavy chain, a constant region (Calpha)
      and 3'-untranslated region of alpha-chain. The Calpha gene contains four constant
      region domains (CH1-CH4). Phylogenetic analysis indicated that goose IgCalpha has
      a close genetic relationship with duck, ostrich and chicken IgCalpha. Three
      dimensional modeling and glycosylation analysis revealed the goose Igalpha is
      consistent with the characterization of immunoglobulin. Western blotting
      suggested the goose IgCalpha has the same antigenicity to natural IgA. In
      general, the identification of goose immunoglobulin not only provides insights
      into the evolution of the Ig heavy-chain gene family, but may also benefit future
      studies of the avian immune system.

PMID- 24322771
TI  - Characterization of AvaR1, an autoregulator receptor that negatively controls
      avermectins production in a high avermectin-producing strain.
AB  - Many gamma-butyrolactone-autoregulator receptors control the production of
      secondary metabolites in Streptomyces spp. Hence, AvaR1, an autoregulator
      receptor protein in Streptomyces avermitilis, was characterized as a negative
      regulator of avermectin (Ave) production. Deletion of AvaR1 in a high-producing
      strain increased production of Ave B1a approx. 1.75 times (~700 MUg/ml) compared
      with the parent strain. Semi-quantitative RT-PCR and electrophoretic mobility
      shift assays revealed that AvaR1 regulates the biosynthesis of Ave but not
      through the aveR pathway-specific regulatory gene. A special signaling molecule,
      avenolide, increased production of Ave. This study has refined our understanding
      of how avenolide regulates the production of Aves which is promising for
      developing new methods to improve the production of antibiotics in industrial
      strains.

PMID- 24322772
TI  - Reversing P-glycoprotein-mediated multidrug resistance in vitro by alpha-asarone
      and beta-asarone, bioactive cis-trans isomers from Acorus tatarinowii.
AB  - P-Glycoprotein (P-gp), an ATP-binding cassette transporter, plays an important
      role in multidrug resistance (MDR). alpha-Asarone and beta-asarone, bioactive cis
      trans isomers found in Acorus tatarinowii Schott, were tested for their potential
      ability to modulate the expression and function of P-gp in Caco-2 cells. MTT
      assays revealed that both alpha-asarone and beta-asarone significantly enhanced
      the vincristine-induced cytotoxicity to cells. beta-Asarone was the most potent.
      Flow cytometry showed that alpha- and beta-asarone increased Rhodamine 123
      (Rh123) uptake and inhibited Rh123 efflux in Caco-2 cells in a concentration
      dependent manner. Furthermore, P-gp expression and P-gp mRNA in cells were
      decreased by exposure to alpha- and beta-asarone. In addition, beta-asarone
      increased the inhibition of P-gp activity in cells more than alpha-asarone. Thus,
      alpha- and beta-asarone effectively reversed MDR by inhibiting P-gp function and
      expression.

PMID- 24322773
TI  - Construction and optimization of a Pseudomonas putida whole-cell bioreporter for
      detection of bioavailable copper.
AB  - A Pseudomonas putida whole-cell bioreporter for detecting bioavailable copper was
      constructed by inserting a CueR-regulated sensor element upstream of a
      promoterless green fluorescent protein (GFP) reporter gene. The constructed
      bioreporter cells expressed GFP only in response to Cu and Ag when cultivated in
      different metal salt solutions. M9 supplemented medium provided higher
      sensitivity compared with LB medium. The optimal test condition was cell
      suspension with an OD600 of 0.4-0.5 incubated at 30  degrees C. The detection
      range of Cu is 1-70 mg/l under optimal test condition in M9 supplemented medium.

PMID- 24322774
TI  - Multiparameter flow cytometry for the characterisation of extracellular markers
      on human mesenchymal stem cells.
AB  - Extracellular surface proteins are used to identify fully-functional human
      mesenchymal stem cells (hMSCs) in a mixed population. Here, a multiparameter flow
      cytometry assay was developed to examine the expression of several bone marrow
      derived hMSC markers simultaneously at the single cell level. The multiparameter
      approach demonstrates a depth of analysis that goes far beyond the conventional
      single or dual staining methods. CD73, CD90 and CD105 were chosen as positive
      markers as they are expressed on multipotent hMSCs, whilst CD34 and HLA-DR were
      chosen as negative indicators. Single colour analysis suggested a population
      purity of 100 %; in contrast, when analysed via the multiparameter method, the
      CD73(+ve)/CD105(+ve)/CD90(+ve)/HLA-DR(-ve)/CD34(-ve) phenotypes represented 94.5
      +/- 1.3 % of the total cell population. Also, although CD271 has been posited as
      a definite early stage hMSC marker, here we show it is not present on pre-passage
      cells, highlighting the need for careful marker selection.

PMID- 24322775
TI  - Comparison of firefly luciferase and NanoLuc luciferase for biophotonic labeling
      of group A Streptococcus.
AB  - NanoLuc luciferase (Nluc) is an engineered enzyme that catalyses the substrate,
      furimazine, to produce light. Nluc has higher sensitivity than the commonly used
      bioluminescent reporter, firefly luciferase (FFluc). We have introduced Nluc into
      a toxin-antitoxin stabilised plasmid for the efficient labeling of group A
      Streptococcus. Comparison of signal strength and kinetic properties between Nluc
      labeled bacteria and similarly previously-labeled FFluc bacteria, showed that the
      bioluminescent signal produced by Nluc-labeled bacteria is up to 15-times higher
      than FFluc-labeled bacteria during the logarithmic phase. However, with Nluc we
      were unable to differentiate between bacteria that are metabolically active and
      inactive because of its ATP-independence. Nluc therefore offers a more sensitive
      reporter but, perhaps, one more restricted for downstream applications.

PMID- 24322776
TI  - A one-pot system for production of L-2-aminobutyric acid from L-threonine by L
      threonine deaminase and a NADH-regeneration system based on L-leucine
      dehydrogenase and formate dehydrogenase.
AB  - L-2-Aminobutyric acid (L-ABA) is an unnatural amino acid that is a key
      intermediate for the synthesis of several important drugs. It can be produced by
      transaminase or dehydrogenase from alpha-ketobutyric acid, which can be
      synthesized enzymatically from the bulk amino acid, L-threonine. Deamination of L
      threonine followed by a hydrogenation reaction gave almost the theoretical yield
      and was estimated to be more cost-effective than the established chemical
      process. L-Threonine deaminase from Escherichia coli, L-leucine dehydrogenase
      from Bacillus cereus, and formate dehydrogenase from Pseudomonas sp. were over
      expressed in E. coli and used for one-pot production of L-ABA with formate as a
      co-substrate for NADH regeneration. 30 mol L-threonine were converted to 29.2 mol
      L-ABA at 97.3 % of theoretical yield and with productivity of 6.37 g l(-1) h(-1)
      at 50 l. This process offers a promising approach to fulfil industrial
      requirements for L-ABA.

PMID- 24322777
TI  - Isolation of adipose-derived stem cells: a comparison among different methods.
AB  - Adipose-derived stromal cells (ASCs) are usually isolated by digestion with
      collagenase. We have compared alternative methods to isolate ASCs in a more
      economically viable protocol. Nine protocols using red blood cells lysis buffer
      solution, trypsin, collagenase and centrifugation were compared; the isolation
      rate, cell viability, expansion rate, immunophenotype and differentiation in
      adipogenic and osteogenic lineages were analyzed. ASCs were isolated and
      successfully maintained by digestion with trypsin. Cells presented similar
      immunophenotypes, adipogenic differentiation and in vitro proliferation but an
      osteogenic differentiation capacity up to seven times higher than ASCs isolated
      by collagenase. This alternative protocol is thus efficient and more cost
      effective than the commonly-used methods and may represent a promising protocol
      for obtaining ASCs for bone tissue engineering.

PMID- 24322778
TI  - Production of tropane alkaloids in Hyoscyamus niger (black henbane) hairy roots
      grown in bubble-column and spray bioreactors.
AB  - Hairy root cultures of Hyoscyamus niger were cultivated in shake-flasks, a bubble
      column bioreactor and a hybrid bubble-column/spray bioreactor and evaluated for
      alkaloid production. The latter gave the highest anisodamine content (0.67 mg/g
      dry wt) whereas scopolamine, hyoscyamine and cuscohygrine concentrations were
      highest in the bubble-column reactor (5.3, 1.6 and 26.5 mg/g dry wt,
      respectively). Both bioreactors gave similar productivities of scopolamine (1 and
      0.98 mg/l day) and cuscohygrine (5 and 5.4 mg/l day), but anisodamine
      productivity was 3.5-fold higher in the hybrid bioreactor (HB) (0.02 and 0.07
      mg/l day, respectively). Elicitation with methyl jasmonate increased scopolamine
      productivity by 146 % in roots grown in the HB whereas their permeabilization
      with DMSO caused 4-, 5-, 25- and 28-fold increase in scopolamine, hyoscyamine,
      anisodamine and cuscohygrine concentrations in the growth medium. In situ
      extraction with Amberlite XAD-2 doubled scopolamine productivity in the hybrid
      reactor after 50 days.

PMID- 24322780
TI  - Selective on/off switching at room temperature of a magnetic bistable {Fe2Co2}
      complex with single crystal-to-single crystal transformation via intramolecular
      electron transfer.
AB  - A cyano-bridged {Fe2Co2} complex shows reversible single crystal-to-single
      crystal transformation between diamagnetic and paramagnetic states switched
      specifically by losing and absorbing methanol at room temperature in the solid
      state. And the solvent loss form presents temperature- and pressure-induced
      intramolecular electron transfer behaviour. 

PMID- 24322781
TI  - The harms of screening: a proposed taxonomy and application to lung cancer
      screening.
AB  - IMPORTANCE: Making rational decisions about screening requires information about
      its harms, but high-quality evidence is often either not available or not used.
      One reason may be that we lack a coherent framework, a taxonomy, for
      conceptualizing and studying these harms. OBJECTIVE: To create a taxonomy, we
      categorized harms from several sources: systematic reviews of screening, other
      published literature, and informal discussions with clinicians and patients. We
      used this information to develop an initial taxonomy and vetted it with local and
      national experts, making revisions as needed. RESULTS: We propose a taxonomy with
      4 domains of harm from screening: physical effects, psychological effects,
      financial strain, and opportunity costs. Harms can occur at any step of the
      screening cascade. We provide definitions for each harm domain and illustrate the
      taxonomy using the example of screening for lung cancer. CONCLUSIONS AND
      RELEVANCE: The taxonomy provides a systematic way to conceptualize harms as
      experienced by patients. As shown in the lung cancer screening example, the
      taxonomy also makes clear where (which domains of harms and which parts of the
      screening cascade) we have useful information and where there are gaps in our
      knowledge. The taxonomy needs further testing and validation across a broad range
      of screening programs. We hope that further development of this taxonomy can
      improve our thinking about the harms of screening, thus informing our research,
      policy making, and decision making with patients about the wisdom of screening.

PMID- 24322782
TI  - Supramolecular organization of functional organic materials in the bulk and at
      organic/organic interfaces: a modeling and computer simulation approach.
AB  - The molecular organization of functional organic materials is one of the research
      areas where the combination of theoretical modeling and experimental
      determinations is most fruitful. Here we present a brief summary of the
      simulation approaches used to investigate the inner structure of organic
      materials with semiconducting behavior, paying special attention to applications
      in organic photovoltaics and clarifying the often obscure jargon hindering the
      access of newcomers to the literature of the field. Special attention is paid to
      the choice of the computational "engine" (Monte Carlo or Molecular Dynamics) used
      to generate equilibrium configurations of the molecular system under
      investigation and, more importantly, to the choice of the chemical details in
      describing the molecular interactions. Recent literature dealing with the
      simulation of organic semiconductors is critically reviewed in order of
      increasing complexity of the system studied, from low molecular weight molecules
      to semiflexible polymers, including the challenging problem of determining the
      morphology of heterojunctions between two different materials. 

PMID- 24322779
TI  - Meckel-Gruber syndrome and the role of primary cilia in kidney, skeleton, and
      central nervous system development.
AB  - The ciliopathies are a group of related inherited diseases characterized by
      malformations in organ development. The diseases affect multiple organ systems,
      with kidney, skeleton, and brain malformations frequently observed. Research over
      the last decade has revealed that these diseases are due to defects in primary
      cilia, essential sensory organelles found on most cells in the human body. Here
      we discuss the genetic and cell biological basis of one of the most severe
      ciliopathies, Meckel-Gruber syndrome, and explain how primary cilia contribute to
      the development of the affected organ systems. 

PMID- 24322783
TI  - Epicardial ablation cures electrical storm caused by cardiac involvement in
      myotonic dystrophia type 2.

PMID- 24322784
TI  - Effect of percutaneous renal denervation on blood pressure level and sympathetic
      activity in a patient with polycystic kidney disease.

PMID- 24322785
TI  - HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse
      reactions: an international study and meta-analysis.
AB  - HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe
      cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and
      systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal
      necrolysis (TEN). We conducted an international study using consensus diagnosis
      criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We
      found that HLA-A*31:01 showed a significant association with CBZ-DRESS in
      Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0
      340)), and the strong association was also found in Chinese (P<0.001; OR (95%
      CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in
      neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong
      association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A
      meta-analysis of this and other published studies confirmed that in all
      populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS
      (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association
      with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that
      HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More
      studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in
      Europeans. Considering the potential clinical utility, the cost-effectiveness of
      the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in
      Chinese needs further investigation. 

PMID- 24322787
TI  - How can we optimize modern imaging techniques for breast cancer, with main
      reference to breast recurrence?

PMID- 24322786
TI  - High warfarin sensitivity in carriers of CYP2C9*35 is determined by the impaired
      interaction with P450 oxidoreductase.
AB  - Cytochrome P450 2C9 (CYP2C9) metabolizes many clinically important drugs
      including warfarin and diclofenac. We have recently reported a new allelic
      variant, CYP2C9*35, found in a warfarin hypersensitive patient with Arg125Leu and
      Arg144Cys mutations. Here, we have investigated the molecular basis for the
      functional consequences of these polymorphic changes. CYP2C9.1 and CYP2C9
      Arg144Cys expressed in human embryonic kidney 293 cells effectively metabolized
      both S-warfarin and diclofenac in NADPH-dependent reactions, whereas CYP2C9
      Arg125Leu or CYP2C9.35 were catalytically silent. However, when NADPH was
      replaced by a direct electron donor to CYPs, cumene hydroperoxide, hereby
      bypassing the CYP oxidoreductase (POR), all variant enzymes were active,
      indicating unproductive interactions between CYP2C9.35 and POR. In silico
      analysis revealed a decrease of the electrostatic potential of CYP2C9-Arg125Leu
      POR interacting surface and the loss of stabilizing salt bridges between these
      proteins. In conclusion, our data strongly suggest that the Arg125Leu mutation in
      CYP2C9.35 prevents CYP2C9-POR interactions resulting in the absence of NADPH
      dependent CYP2C9-catalyzed activity in vivo, thus influencing the warfarin
      sensitivity in the carriers of this allele. 

PMID- 24322788
TI  - Biological subtypes of breast cancer: current concepts and implications for
      recurrence patterns.
AB  - Breast cancer is comprised of a number of complex and heterogeneous subtypes with
      differing clinical behavior and outcomes. In recent years, significant advances
      have been made in discerning the molecular drivers of this disease, and
      characterizing distinct subtypes of breast cancer based on gene expression
      profiles. These advances have begun to translate into greater individualization
      of treatment for patients. Although these advances have shaped our understanding
      of the underlying biology of breast cancer, most clinical decisions are currently
      based on tumor expression of the estrogen receptor (ER), progesterone receptor
      (PR) and the human epidermal growth factor receptor 2 (HER2). These biomarkers
      have prognostic and predictive significance in breast cancer and have important
      implications for tumor growth and metastatic patterns. In this review, we focus
      on the three broad phenotypes of breast cancer used in clinical practice; ER/PR
      positive, HER2 positive and triple negative breast cancer (TNBC), which is
      characterized by lack of expression of ER, PR and HER2. We discuss the influence
      of these tumor-related factors as well as histological subtype, on the potential
      for breast cancer recurrence and patterns of disease spread. 

PMID- 24322789
TI  - Structural, pathophysiological and clinical aspects of diagnostic imaging in
      breast recurrence: the breast after treatment.
AB  - In the last decades the outcome of women with breast cancer has been
      significantly modified partially as a result of screening which has facilitated
      earlier diagnosis and consequently allowed a conservative surgical approach.
      Today diagnostic imaging is generally based on Mammography (Mx), with a minor
      role for ultrasounds and Magnetic Resonance (MR). In this scenario, dominated by
      morphostructural techniques, there is a secondary role for radionuclide
      procedures both using gamma emitters or Positron Emission Tomography (PET) with F
      18 Fluorodeoxyglucose (FDG) or other radiotracers beyond FDG. After surgery and
      allied treatments, including radiotherapy, the diagnosis of breast recurrence has
      become a difficult challenge, because of the several factors simultaneously
      and/or sequentially involved. In the diagnosis of local recurrence, Mx remains
      the first diagnostic step together with a clinical visit, as alternative
      approaches yield more unsatisfactory results. Nevertheless as Mx is affected by a
      low sensitivity, it is important to better evaluate the capabilities of
      functional imaging utilizing MR and Nuclear Medicine, to allow an earlier and
      more accurate detection. In this paper we analyze structural, pathophysiological
      and the clinical background to diagnostic imaging in local breast recurrence to
      better understand basic problems, to facilitate more effective utilization of
      diagnostic tools. 

PMID- 24322790
TI  - Post breast conservation therapy imaging and local recurrence.
AB  - Breast conservation therapy, which includes lumpectomy usually followed by breast
      irradiation, is an effective and commonly used therapy for women with resectable
      breast cancers. Although the rate of local recurrence has decreased over the
      years, these women continue to be at risk with an overall incidence of local
      recurrence of 1-2% per year for 10 years. The incidence of local recurrence
      varies according to age and receptor status. Studies have shown that early
      detection of in breast recurrence or second primaries reduces mortality.
      Mammography and clinical breast examination can be effective in the detection of
      recurrence. The efficacy of mammography, recommended intervals for screening and
      the various mammographic appearances of recurrence are addressed in this paper.
      Other breast imaging modalities including breast ultrasound and breast magnetic
      resonance imaging have less of a defined role. There is little data on ultrasound
      in this setting and the available data on magnetic resonance imaging after breast
      conservation therapy is evolving and will be presented. Finally, benign disease
      mimicking tumor recurrence and commonly missed appearance of tumor recurrence are
      discussed. 

PMID- 24322791
TI  - Molecular breast imaging with gamma emitters.
AB  - Following a diagnosis of breast cancer (BC), the early detection of local
      recurrence is important to define appropriate therapeutic strategies and increase
      the chances of a cure. In fact, despite major progress in surgical treatment,
      radiotherapy, and chemotherapy protocols, tumor recurrence is still a major
      problem. Moreover, the diagnosis of recurrence with conventional imaging methods
      can be difficult as a result of the presence of scar tissue. Molecular breast
      imaging (MBI) with gamma-ray emitting radiotracers may be very useful in this
      clinical setting, because it is not affected by the post-therapy morphologic
      changes. This review summarises the applications of 99mTc-sestamibi and 99mTc
      tetrofosmin, the two most employed gamma emitter radiopharmaceuticals for MBI, in
      the diagnosis of local disease recurrence in patients with BC. The main
      limitation of MBI using conventional gamma-cameras is the low sensitivity for
      small BCs. The recent development of hybrid single photon emission computed
      tomography/computed tomography devices and especially of high-resolution specific
      breast cameras can improve the detection rate of sub-centimetric malignant
      lesions. Nevertheless, probably only the large availability of dedicated cameras
      will allow the clinical acceptance of MBI as useful complementary diagnostic
      technique in BC recurrence. The possible role of MBI with specific cameras in
      monitoring the local response of BC to neoadjuvant chemotherapy is also briefly
      discussed. 

PMID- 24322792
TI  - Recurrent and metastatic breast cancer PET, PET/CT, PET/MRI: FDG and new
      biomarkers.
AB  - Primary breast cancer often displays only moderately increased glucose metabolism
      resulting in a low sensitivity of positron emission tomography (PET) using [F
      18]fluorodeoxyglucose (FDG) in detecting small breast carcinomas, locoregional
      micrometastases and non-enlarged tumor infiltrated lymphnodes. In contrast,
      distant breast cancer metastases are generally characterized by significantly
      increased metabolic activity compared to normal tissue. Therefore, FDG-PET
      provides accurate diagnostic information as a whole body imaging modality in
      staging of breast cancer patients. The metabolic information from FDG-PET/CT is
      often more sensitive than conventional imaging for the detection of distant
      metastases, particularly in the recurrent setting. FDG-PET is superior in
      detecting tumor-involved distant lymphnodes, particularly those which are normal
      in size, as well as in characterizing enlarged lymphnodes as positive or negative
      for malignancy. Of note, CT is superior in detecting small lung metastases.
      Although the overall sensitivity for bone scintigraphy and FDG-PET are
      comparable, bone scintigraphy seems to be superior in the detection of
      osteoblastic disease whereas FDG-PET is superior for osteolytic metastases,
      suggesting a complementary role for both imaging procedures. FDG-PET/MR has an
      evolving role in breast cancer management, for example in the detection of liver
      metastases and in the research setting for treatment monitoring. The utilization
      of PET for prediction of treatment response to primary chemotherapy is an area of
      active research, using FDG as well as other PET biomarkers including [F
      18]Fluoroestradiol, [F-18]Fluorothymidine and integrin targeting tracer for
      monitoring anti-angiogenic therapy. 

PMID- 24322793
TI  - Current and future perspectives in diagnostic imaging as a guide to
      targeted/local therapies in breast cancer recurrence.
AB  - In recent years, a multidisciplinary approach for breast cancer patient
      management has been adopted to provide an accurate evaluation of
      primary/recurrent tumor and to guiding appropriate treatment. The introduction of
      positron emission tomography (PET) and PET/computed tomography (CT) with 18F
      fluorodeoxyglucose and other radiolabelled molecules for the early detection of
      breast cancer recurrence has important consequences both for staging and
      treatment planning. In particular, in the last few years, research efforts have
      been made to guide targeted or local therapies directing against the cancer
      outgrowth. Based on the available data in the literature, in the present review,
      we will discuss 1) the role of PET and PET/CT in guiding local therapies for
      breast cancer recurrences, (both loco-regional and distant sites); and 2) its
      current status in clinical practice and its possible future role. 

PMID- 24322794
TI  - The future of imaging for breast cancer recurrence.

PMID- 24322795
TI  - Radioguided occult lesion localization of cervical recurrences from
      differentiated thyroid cancer: technical feasibility and clinical results.
AB  - AIM: We explored the feasibility of radioguided occult lesion localization (ROLL)
      for radioiodine-negative cervical recurrences from differentiated thyroid cancer
      (DTC). METHODS: The procedure was performed in 32 patients (3 patients being
      operated twice); 15/32 patients had had multiple prior lymph node dissections
      ("hostile" anatomy). 99mTc-albumin macro-aggregates (99mTc-MAA) were injected
      intra-lesionally under ultrasound guidance; 2 to 18 hours later, a hand-held
      gamma-probe helped to localize the lesions intraoperatively and to ascertain
      removal of the radiolabeled lesions. Mini-invasive excision of the radiolabelled
      lesions was performed in 12 cases (m-ROLL), while a modified radical neck
      dissection was performed in 23 cases after radioguided lymphadenectomy (d-ROLL).
      Fifty-nine lesions were radiolabelled (mean size 11+/-4.5 mm). RESULTS:
      Radioguidance allowed to identify/remove 56/59 lesions (95%). Some leakage of
      99mTc-MAA in the surrounding tissues hampered detection of 3 lesions, which were
      removed anyway (100% overall localization). Histopathology confirmed metastatic
      involvement of the radiolabeled lesions and some additional metastases in other
      nodes. Neither nerve injury nor hypoparathyroidism occurred. After a median
      follow-up of 29 months, 19 patients were disease-free, 12 patients developed loco
      regional recurrences, 1 patient had distant metastases and 1 patient had both
      loco-regional and distant metastases. Recurrences rates were 33% for m-ROLL and
      40% for d-ROLL. CONCLUSIONS: The ROLL technique is feasible in selected patients
      with loco-regional recurrence from DTC, proving to be particularly useful also in
      patients already submitted to cervical dissections and/or with small lesions
      located in surgically difficult sites. It can therefore have a clinical role in
      the management of cervical DTC recurrences.

PMID- 24322796
TI  - Comparison of hydrogen production and electrical power generation for energy
      capture in closed-loop ammonium bicarbonate reverse electrodialysis systems.
AB  - Currently, there is an enormous amount of energy available from salinity
      gradients, which could be used for clean hydrogen production. Through the use of
      a favorable oxygen reduction reaction (ORR) cathode, the projected electrical
      energy generated by a single pass ammonium bicarbonate reverse electrodialysis
      (RED) system approached 78 W h m(-3). However, if RED is operated with the less
      favorable (higher overpotential) hydrogen evolution electrode and hydrogen gas is
      harvested, the energy recovered increases by as much ~1.5* to 118 W h m(-3).
      Indirect hydrogen production through coupling an RED stack with an external
      electrolysis system was only projected to achieve 35 W h m(-3) or ~1/3 of that
      produced through direct hydrogen generation.

PMID- 24322797
TI  - Second-harmonic reflection imaging of normal and accelerated corneal crosslinking
      using porcine corneas and the role of intraocular pressure.
AB  - PURPOSE: The aim of this study was to investigate morphological changes, using
      second-harmonic (SH) optical imaging, in the corneal stroma after normal- and
      high-intensity collagen crosslinking in postmortem enucleated porcine eyes at
      controlled intraocular pressures (IOPs). METHODS: Reflection-mode SH optical
      imaging of the stroma was realized after standard collagen cross-linking (CXL)
      and accelerated crosslinking (AXL) of porcine corneas, and the results were
      compared with the results for untreated controls. Ultraviolet-X lamps (365 nm)
      were used during riboflavin crosslinking with intensities of 3, 10, 30, and 100
      mW/cm2 for constant 5.4-J/cm2 exposure doses. The IOP was varied using saline
      solution injected through the optic nerve and monitored using a Schiotz
      tonometer. SH optical imaging was realized with an in-house build multiphoton
      microscope using an ultrafast dispersion-compensated Ti-sapphire laser. RESULTS:
      SH reflection images of CXL and AXL porcine corneas obtained at IOPs of 8, 11,
      16, and 26 mm Hg showed a similar fibrillar structure of collagen lamellae. All
      crosslinked corneas showed an increased fibrillar contrast in comparison with
      untreated baseline images. At low IOPs, strong variations in the scattering were
      observed that reduced with an increase in the IOP, when fibrils tended to
      straighten out. At low and normal IOPs, no significant difference between CXL and
      AXL results could be observed. At very elevated IOPs, however, the impact of AXL
      was found to alter the fibrillar structure of the collagen becoming less apparent
      in SH images when compared with that of CXL. CONCLUSIONS: We found a strong
      influence of the IOP on SH reflection imaging of postmortem porcine corneal
      stroma. CXL and AXL led to similar SH images indicative of a similar tensile
      strength. Only at very elevated IOPs (26 mm Hg) did the results for AXL deviate
      from those of CXL, suggesting an IOP-related threshold for reliable applications
      of AXL.

PMID- 24322798
TI  - Outcomes of therapeutic penetrating keratoplasty from a tertiary eye care centre
      in northern India.
AB  - PURPOSE: The aim was to study the outcomes and results of therapeutic penetrating
      keratoplasty (Th PK) at a tertiary eye care hospital in northern India. METHODS:
      In this retrospective interventional study, a cohort of 506 eyes that underwent a
      Th PK for microbial keratitis was evaluated. Th PK was performed in cases of
      recalcitrant microbial keratitis with impending perforation (descemetocele
      formation) or perforation (>3 mm). Medical records were reviewed for demographic
      details, risk factors, ulcer and perforation size, microbiological
      investigations, size of donor and recipient beds, postoperative complications,
      and anatomical and visual outcomes. RESULTS: Anatomical success was seen in 454
      eyes (89.7%). Preoperatively, the corrected distance visual acuity was <3/60 in
      495 eyes (97.8%); after performing the Th PK, the corrected distance visual
      acuity was <3/60 in 249 eyes (49.2%), 3/60 to 6/60 in 182 eyes (35.9%), and >6/60
      in 75 eyes (14.8%). Eyes with smaller grafts (<9 mm) had better anatomical and
      visual outcomes compared with eyes with larger grafts (9-11 mm; P = 0.03 and >11
      mm; P = 0.0). A higher success rate was achieved with pure bacterial or fungal
      organisms rather than with mixed infections. A higher incidence of secondary
      glaucoma was seen in eyes with perforated ulcers (29.36%; 111/378) than in eyes
      without perforation (11.71%; 15/128) (P <.01) and in eyes with larger graft sizes
      (>11 mm and 9-11 mm) than in eyes with smaller graft sizes (<9 mm) (P <0.01).
      CONCLUSIONS: Th PK has a definitive role in the management of severe and
      refractory keratitis with a high success in restoring anatomical integrity and
      providing useful vision. Better outcomes may be achieved with early intervention
      before perforation or limbal/scleral extension.

PMID- 24322799
TI  - Simultaneous surgery for corneal edema and aphakia: DSEK and placement of a
      retropupillary iris claw lens.
AB  - PURPOSE: The aim was to report the surgical outcomes of simultaneous Descemet
      stripping endothelial keratoplasty (DSEK) with a retropupillary fixated iris claw
      lens in patients with aphakic corneal edema without capsular support. METHODS:
      The clinical records of aphakic patients with corneal edema and no capsular
      support who underwent a combined DSEK and implantation of a retropupillary
      fixated iris claw lens (Artisan) were evaluated. Presurgical and postsurgical
      best-corrected visual acuity, postsurgical refraction, and endothelial cell count
      were analyzed at the first and sixth months after the surgery and were imaged
      with anterior segment ultrasound biomicroscopy. RESULTS: A total of 9 eyes from 7
      females and 2 males were analyzed. The average age was 72.1 years. The mean
      duration of the postoperative follow-up was 7.7 months. All the patients achieved
      corrected visual acuities over 0.60 logarithm of the minimum angle of resolution.
      There was no significant variation in the endothelial count between the first and
      sixth months. Astigmatism >1 D was induced in all the patients, with 7 patients
      having against the rule, and 2 patients having oblique astigmatism. CONCLUSIONS:
      DSEK combined with a retropupillary fixated iris claw lens was shown to be a safe
      surgical technique in patients with aphakia without capsular support and corneal
      swelling. This surgery resulted in stable endothelial cell counts during the
      first 6 months after the surgery and an improvement in visual acuity.

PMID- 24322800
TI  - Very low risk of light-induced retinal damage during Boston keratoprosthesis
      surgery: a rabbit study.
AB  - PURPOSE: The aim of this study was to assess the possibility of light damage to
      the retina by a surgical microscope during implantation of a Boston
      Keratoprosthesis (B-KPro) in rabbits. METHODS: The retinal irradiance from a
      Zeiss OPMI Lumera S7 operating microscope was measured at the working distance
      (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro
      was implanted into 1 eye of 12 rabbits with the optic covered during the
      procedure. The operated eyes were then continuously exposed to a fixed light
      intensity under the microscope for 1 hour. Fluorescein angiography was carried
      out on days 2 and 9 postsurgery, after which the animals were euthanized.
      Further, we compared the potential of these retinal exposures to well-accepted
      light safety guidelines applicable to humans. RESULTS: Light transmittance of B
      KPro revealed a blockage of short wavelengths (<390 nm) and of long wavelengths
      (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of
      the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography
      nor a histological examination showed any morphological retinal changes in our
      rabbits. Moreover, the retinal exposures were well below the safety limits.
      CONCLUSIONS: Modern surgical microscopes have filters incorporated in them that
      block the most damaging wavelengths of light. The B-KPro is made of 100%
      poly(methyl methacrylate), which makes it in itself a blocker of short
      wavelengths of light. No damage could be demonstrated in the animal study, and
      the retinal exposures were well below the safety limits. Together, these results
      suggest that light exposures during B-KPro surgery present a low risk of
      photochemical damage to the retina.

PMID- 24322801
TI  - Is there a relationship between pathologic myopia and dry eye syndrome?
AB  - PURPOSE: The aim of this study was to investigate the relationship between
      pathologic myopia and the dry eye syndrome. METHODS: Forty-five patients with a
      spherical equivalence (SE) greater than -6.0 diopters (D) and an axial length
      (AL) >26.5 mm were assigned to the pathological myopia group (group 1). Forty
      four healthy individuals were selected from subjects with emmetropia whose SE
      values ranged from -1.0 to +1.0 D (group 2). Ocular surface disease index (OSDI)
      scores of all the patients were determined. All the participants underwent the
      following: Schirmer 1 test without anesthesia, corneal staining, tear break-up
      time (TBUT), Schirmer 1 test with anesthesia, and AL measurement. RESULTS: The
      mean age of group 1 and group 2 patients was 40.2 +/- 12.3 and 38.8 +/- 9.3
      years. The mean values of SE, keratometry, and AL were -9.6 +/- 3.8 D, 43.9 +/-
      1.1 D, and 27.4 +/- 0.6 mm in group 1 and -0.1 +/- 0.5 D, 42.3 +/- 1.4 D, and
      23.0 +/- 0.2 mm in group 2. The mean values of the Schirmer 1 test without and
      with anesthesia were 14.4 +/- 6.1 and 9.5 +/- 4.5 mm in group 1 and 16.7 +/- 6.2
      and 11.4 +/- 6.0 mm in group 2. The mean TBUT in group 1 was 7.2 +/- 3.4 seconds,
      whereas that in group 2 was 13.6 +/- 3.7 seconds. There was a significant
      difference between the groups in SE, keratometry, AL, TBUT, and OSDI scores (P <
      0.001). CONCLUSIONS: Patients with pathologic myopia have lower TBUT scores and
      higher OSDI scores when compared with healthy individuals.

PMID- 24322802
TI  - Obesity and obstructive sleep apnea in patients with keratoconus in a Turkish
      population.
AB  - PURPOSE: The aim of this study was to compare the frequency of occurrence of
      obesity and high risk of developing obstructive sleep apnea (OSA) in a
      keratoconus population with that of a control group. METHODS: This prospective,
      case-controlled multicenter study was performed on patients with keratoconus and
      age- and gender-matched control subjects. One hundred forty-six patients were
      included in each group, and the Berlin Questionnaire was used for classifying
      patients as having a high risk or low risk of developing OSA. The patients'
      demographic and clinical characteristics were compared with the Mann-Whitney U
      test for continuous variables and with the chi test for categorical variables.
      RESULTS: The keratoconus (85 male/61 female) and control (79 male/67 female)
      groups' median ages were 25 (8-65) and 24 (9-60) years, respectively. Of the 146
      patients in each group, 11 (7.5%) patients were determined to be at a high risk
      of developing OSA in the keratoconus group, and 8 (5.5%) patients were determined
      to be at a high risk of developing OSA in the control group. There was no
      significant difference between the groups (P = 0.477). The keratoconus and
      control groups' median body mass index values were found to be within normal
      ranges of 23.2 and 23.4, respectively. CONCLUSIONS: In this study, the mean body
      mass index value of the keratoconus group was determined to be within normal
      limits. In a Turkish population, the ratio of a high risk of developing OSA was
      not found to be significantly different between the keratoconus and control
      groups.

PMID- 24322803
TI  - Surgical approach with high-frequency radiowave electrosurgery for superior
      limbic keratoconjunctivitis.
AB  - PURPOSE: The aim was to introduce the application of a simple technique using
      high-frequency radiowave electrosurgery in the management of superior limbic
      keratoconjunctivitis (SLK). METHODS: This study is a prospective, noncomparative,
      interventional case series analysis. Seven patients (9 eyes) with SLK were
      recruited from the outpatient clinic of the Department of Ophthalmology,
      Severance Eye Hospital and Kangbuk Samsung Hospital, Seoul, Korea. On the
      superior bulbar conjunctiva, multiple ablations were performed using a high
      frequency radiowave electrosurgical unit (Ellman Surgitron Dual Frequency RF;
      Ellman International, Inc, Hewlett, NY) with the lowest power setting of 1 (of
      100) in the cutting mode. The operation was completed when the operator found no
      redundant portion on the superior bulbar conjunctiva. RESULTS: After the surgery
      was performed, all the patients had mild to moderate superior conjunctival
      injection and swelling at the operating area. One month postoperatively, slit
      lamp examinations revealed a smooth conjunctival surface without remarkable
      hyperemia. The symptoms were significantly improved in all eyes. Follow-up
      Fourier domain optical coherence tomography images showed a decrease of the space
      between subconjunctival tissue and sclera. No notable complications were
      observed. CONCLUSIONS: This study demonstrated that high-frequency radiowave
      electrosurgery is a simple, safe, and effective first-line surgical treatment
      modality for refractory SLK patients with conjunctivochalasis.

PMID- 24322804
TI  - Clinical characteristics of Acanthamoeba keratitis infections in 28 states, 2008
      to 2011.
AB  - PURPOSE: The aim was to describe a geographically and clinically diverse sample
      of cases of Acanthamoeba keratitis (AK) and establish the risk factors for poor
      outcomes among patients with this disease. METHODS: We conducted a retrospective,
      population-based case series of 116 patients with AK identified through a
      national surveillance network. Data were collected via a medical record review by
      diagnosing ophthalmologists and by phone interviews with patients. Exact logistic
      regression modeling was used to determine risk factors for poor visual outcomes.
      RESULTS: Among patients with data available on contact lens use, it was found
      that 93.3% wore contact lenses. The median time from symptom onset to care
      seeking was 2 days, whereas the median time from symptom onset to diagnosis was
      27 days. Keratoplasty was performed in 27 of 81 patients with available outcome
      data and was more likely in patients >40 years old [odds ratio (OR) 5.25, 95%
      confidence interval (CI) 1.49-21.92]. When adjusted for age, the risk factors for
      keratoplasty included the presence of a ring infiltrate (OR 40.00, 95% CI 3.58
      447.0) or any sign of stromal invasion (OR 10.48, 95% CI 2.56-55.09). One-third
      of patients with available data on best-corrected visual acuity had a best
      corrected visual acuity <20/200, with the presence of a ring infiltrate as the
      only significant predictor of this outcome when adjusted for age (aOR 3.45, 95%
      CI 1.01-12.31). CONCLUSIONS: AK remains challenging to diagnose. Consequently,
      patients with advanced disease are more likely to have poor outcomes,
      particularly if they are older. The increasing awareness of AK among general eye
      care providers may shorten referral times and potentially improve outcomes.

PMID- 24322805
TI  - Implantation of a complete intrastromal corneal ring at 2 different stromal
      depths in keratoconus.
AB  - PURPOSE: The aim of this study was to evaluate the clinical outcomes of
      intrastromal MyoRing (Dioptex, GmbH, Linz, Austria) implantation at 2 different
      depths of 250 and 300 MUm. METHODS: This was a prospective interventional
      randomized controlled trial, a pilot study. Keratoconic patients with keratometry
      values between 48 and 52 diopters were randomly divided into 2 groups. A
      continuous intrastromal corneal ring of the same size was implanted at 2
      different stromal depths of 250 MUm (group 1) and 300 MUm (group 2) using
      femtosecond laser technology for both groups. Visual and refractive outcomes,
      keratometry, corneal biomechanical characteristics, and higher order aberrations
      were compared at the 1-year postoperative follow-up. RESULTS: In both groups,
      uncorrected distance visual acuity significantly improved after MyoRing
      implantation, whereas neither of these showed any improvement in the corrected
      distance visual acuity. In addition, the mean central keratometry and spherical
      and cylindrical refraction reduced significantly in both groups, and spherical
      aberration increased significantly in both groups. On one hand, coma was reduced
      almost significantly in both groups, and on the other hand, corneal hysteresis
      and corneal resistance factor did not change significantly after the operation.
      None of the patients in both groups had intraoperative or postoperative
      complications. There were no differences observed in any of the measured
      variables of the 2 study groups. CONCLUSIONS: An implantation depth of 250 MUm
      has comparable outcomes with the previously applied 300-MUm implantation depth.
      It may be appropriate for selected cases of keratoconus with lower pachymetry.

PMID- 24322806
TI  - Relationship between IL1beta-511C>T and ILRN VNTR polymorphisms and keratoconus.
AB  - PURPOSE: The aim of this study was to evaluate the relationship between
      keratoconus (KC) and interleukin-1beta (IL1 beta) (-511C>T) and interleukin-1
      receptor antagonist (IL1RN) variable number of tandem repeat (VNTR) polymorphisms
      that are potentially associated in their genetic susceptibility to KC. METHODS: A
      total of 121 patients with KC and 121 healthy individuals were enrolled. Blood
      samples with ethylenediamine tetraacetic acid were obtained, and IL1beta (
      511C>T) (rs16944) (polymerase chain reaction-restriction fragment length
      polymorphism method) and IL1RN VNTR polymorphisms (rs2234663) (polymerase chain
      reaction and agarose gel imaging) were investigated. RESULTS: Genotype and allele
      distribution for IL1beta (-511C>T) and IL1RN VNTR polymorphisms among the KC and
      healthy groups showed no difference (for all; P > 0.05). CONCLUSIONS: Because the
      genotype and allele frequency of both polymorphisms are identical, it is most
      likely that IL1beta-511C>T and IL1RN VNTR polymorphisms do not play a role in the
      development of KC in the Turkish population.

PMID- 24322807
TI  - Outcomes after DSEK in 101 eyes with previous trabeculectomy and tube shunt
      implantation.
AB  - PURPOSE: The aim of this study was to determine the outcomes after Descemet
      stripping endothelial keratoplasty (DSEK) in eyes with previous glaucoma surgery.
      METHODS: This is a retrospective review of all DSEK procedures performed by 2
      surgeons from May 1, 2006, to December 31, 2012. RESULTS: Four hundred sixty-two
      DSEK procedures were performed, of which 113 (24%) were performed in 101 eyes
      after a trabeculectomy (52 procedures) and/or tube shunt implantation (76
      procedures) (15 procedures in eyes with both). Primary graft failure and donor
      dislocation developed in 4.4% and 14.2% of cases in eyes with previous glaucoma
      surgery, not significantly different from the 3.2% (P = 0.56) and 11.5% (P =
      0.51) in eyes without prior glaucoma surgery. During a mean follow-up of 20.7 +/-
      17.6 months, endothelial rejection developed in a greater percentage of eyes with
      previous glaucoma surgery (12.9%; 0.069/eye-year) compared with that in eyes
      without surgery (6.9%; 0.042/eye-year), although the difference was not
      statistically significant (P = 0.066 for percentage of eyes; P = 0.16 for
      rejection rate). Secondary graft failure developed in a significantly higher
      percentage of eyes with previous glaucoma surgery (15.9%; 0.094/eye-year)
      compared with that in eyes without surgery (3.2%; 0.019/eye-year) (P < 0.0001; P
      < 0.0001). Elevated intraocular pressure after DSEK was significantly more common
      in eyes with medically treated glaucoma (41.3%; 0.345/eye year) than in eyes with
      a previous glaucoma surgery (23.8%; 0.145/eye-year) and without glaucoma (20.0%;
      0.138/eye year) (P = 0.009; P = 0.007). CONCLUSIONS: Although intraoperative and
      early postoperative complications such as donor dislocation and primary graft
      failure are not significantly more common after DSEK in eyes with previous
      glaucoma surgery, secondary graft failure is. In contrast, other postoperative
      complications such as elevated intraocular pressure are significantly more common
      in eyes with medically treated glaucoma than in eyes with previous glaucoma
      surgery and without glaucoma.

PMID- 24322808
TI  - Evaluation of the Pentacam ray tracing method for the measurement of central
      corneal power after myopic photorefractive keratectomy.
AB  - PURPOSE: The study evaluated the ray tracing method [total corneal refractive
      power (TCRP)] in a Pentacam apparatus (Oculus, Wetzlar, Germany) for
      postoperative keratometry measurement after myopic photorefractive keratectomy
      (PRK). METHODS: Manifest refraction (MR) and Pentacam analyses were performed
      preoperatively and at 6 months postoperatively after the PRK (STAR S4 IR
      CustomVue; Abbott Medical Optics/Visx) in 49 right eyes from 49 patients (age,
      25.42 +/- 3.51 years). Postoperative corneal power was calculated using the
      clinical history method (CHM) and compared with postoperatively measured
      simulated keratometry (simK), true net power (TNP) at 3 mm, and pupil-centered
      TCRP at the center, 1, 3, and 4 mm (TCRP0, TCRP1, TCRP3, and TCRP4). Vertex
      distance-adjusted refractive change (delta-MR) at the corneal plane was also
      compared with various keratometric changes (delta-K). RESULTS: Postoperative
      TCRP0, TCRP1, TCRP3, and TCRP4 showed no significant difference compared with
      that of the CHM. Postoperative simK was significantly higher than that of the
      CHM, whereas the TNP was significantly lower compared with that of the CHM. The
      delta-Ks measured by simK, TNP, and TCRPs were significantly smaller than delta
      MR, and delta-TCRP4 showed the least difference [mean +/- SD, 0.28 +/- 0.55
      diopters (D)] with delta-MR. The 95% limit of agreement between delta-MR and
      delta-TCRP4 was -0.85 to 1.31 D. The difference between delta-TCRP4 and delta-MR
      was <0.5 D in 55.1% and <1.0 D in 87.8% of the eyes studied. CONCLUSIONS:
      Although postoperative TCRPs showed no significant difference with CHM, delta-MR
      was still underestimated after myopic PRK.

PMID- 24322809
TI  - Treatment of pseudodendrites in herpes zoster ophthalmicus with topical
      ganciclovir 0.15% gel.
AB  - PURPOSE: There is no standard of treatment for epithelial pseudodendrites in
      herpes zoster ophthalmicus (HZO). The purpose of this study is to report the
      topical antiviral drug, 0.15% ganciclovir for treatment of these lesions.
      METHODS: This is a retrospective, interventional case series of 4 patients who
      were diagnosed with HZO epithelial pseudodendrites despite being given oral
      antiviral treatment and who underwent 0.15% ganciclovir gel topical treatment.
      Main outcome measures included epithelial healing time, visual acuity, and
      corneal sensation. RESULTS: All 4 patients were immunocompetent and had
      epithelial lesions unresponsive to antiviral treatment with oral valacyclovir.
      Treatment with topical 0.15% ganciclovir gel 5 times a day resulted in the
      lesions healing successfully within 7 days with improved visual acuity in 3
      patients and an increase in corneal sensation in 2 of the 4 patients.
      CONCLUSIONS: Topical 0.15% ganciclovir gel, 5 times a day until pseudodendritic
      lesion healing and tapering to bid for 2 to 4 weeks thereafter, is an effective
      treatment for pseudodendrites in HZO-affected cases that are often a challenge to
      manage with other oral or topical antivirals.

PMID- 24322810
TI  - Sodium reduction: an important public health strategy for heart health.

PMID- 24322811
TI  - Integrating sodium reduction strategies in the procurement process and
      contracting of food venues in the County of Los Angeles government, 2010-2012.
AB  - Since sodium is ubiquitous in the food supply, recent approaches to sodium
      reduction have focused on increasing the availability of lower-sodium products
      through system-level and environmental changes. This article reviews integrated
      efforts by the Los Angeles County Sodium Reduction Initiative to implement these
      strategies at food venues in the County of Los Angeles government. The review
      used mixed methods, including a scan of the literature, key informant interviews,
      and lessons learned during 2010-2012 to assess program progress. Leveraging
      technical expertise and shared resources, the initiative strategically
      incorporated sodium reduction strategies into the overall work plan of a
      multipartnership food procurement program in Los Angeles County. To date, 3
      County departments have incorporated new or updated nutrition requirements that
      included sodium limits and other strategies. The strategic coupling of sodium
      reduction to food procurement and general health promotion allowed for
      simultaneous advancement and acceleration of the County's sodium reduction
      agenda. 

PMID- 24322812
TI  - Sodium-reduction strategies for meals prepared for older adults.
AB  - This article describes lessons learned from implementing sodium-reduction
      strategies in programs that provide meals to older adults in 2 New York counties,
      with one county replicating the approaches of the other. The implemented sodium
      reduction strategies were product substitutions, recipe modifications, and
      cooking from scratch. Both counties were able to achieve modest sodium reductions
      in prepared meals. Lessons learned to implement sodium reduction strategies
      include the following: (1) identifying partners with shared experience and common
      goals; (2) engaging experts; (3) understanding the complexity of the meals system
      for older adults; (4) conducting sodium nutrient analysis; (5) making gradual and
      voluntary reductions to sodium content; and (6) working toward sustainable sodium
      reduction. 

PMID- 24322813
TI  - Reducing sodium across the board: a pilot program in Schenectady County
      independent restaurants.
AB  - Excess sodium intake can lead to increased blood pressure. Restaurant foods
      contribute nearly a quarter of the sodium consumed in the American diet. The
      objective of the pilot project was to develop and implement in collaboration with
      independent restaurants a tool, the Restaurant Assessment Tool and Evaluation
      (RATE), to assess efforts to reduce sodium in independent restaurants and measure
      changes over time in food preparation categories, including menu, cooking
      techniques, and products. Twelve independent restaurants in Schenectady County,
      New York, voluntarily participated. From initial assessment to a 6-month follow
      up assessment using the RATE, 11 restaurants showed improvement in the cooking
      category, 9 showed improvement in the menu category, and 7 showed improvement in
      the product category. Menu analysis conducted by the Schenectady County Health
      Department staff suggested that reported sodium-reduction strategies might have
      affected approximately 25% of the restaurant menu items. The findings from this
      project suggest that a facilitated assessment, such as the RATE, can provide a
      useful platform for independent restaurant owners and public health practitioners
      to discuss and encourage sodium reduction. The RATE also provides opportunities
      to build and strengthen relationships between public health care practitioners
      and independent restaurant owners, which may help sustain the positive changes
      made.

PMID- 24322814
TI  - Use of environmental change strategies to facilitate sodium reduction: a case
      study in a rural California school district.
AB  - CONTEXT: Excess sodium consumption increases the risk for hypertension, which is
      a leading risk factor for cardiovascular disease. For children and teenagers,
      school meals are a significant source of sodium consumption. OBJECTIVE: To
      describe the environmental change strategies that were implemented to reduce
      sodium in the school meals of a rural California school district. DESIGN:
      Descriptions of the environmental strategies, with an emphasis on staff training
      and infrastructure improvements. SETTING: School district of approximately two
      thousand 9th- to 12th-grade students in rural, northern California. PARTICIPANTS:
      School administration and food service staff at the 5 high schools in Anderson
      Union High School District. INTERVENTION: Shasta County Public Health partnered
      with Anderson Union High School District to (1) facilitate changes to meal
      preparation practices, (2) improve cafeteria infrastructure, and (3) provide
      training and technical assistance to improve procurement strategies. RESULTS:
      Environmental strategies to reduce sodium in school meals were implemented in
      2011. Anderson Union High School District has continued to successfully implement
      scratch cooking and improve procurement strategies to reduce sodium in school
      meals. CONCLUSION: Using an approach that includes environmental change
      strategies can lead to sodium reduction in a school setting.

PMID- 24322815
TI  - Evaluating changes to sodium content in school meals at a large, urban school
      district in Los Angeles County, California.
AB  - CONTEXT: Children consume more than one-third of their daily food intake in
      schools, suggesting that these environments are ideal places for intervening on
      poor dietary behaviors. OBJECTIVE: To assess the impact of strategy-focused menu
      planning on the sodium content of student meals served in the Los Angeles Unified
      School District (LAUSD). DESIGN: Pre- and post-LAUSD menu change analyses for
      school years (SY) 2010-2011 and 2011-2012 were performed using nutritional
      analysis data and food production records. The analyses assessed changes in
      sodium content by meal categories. SETTING: 900+ schools, grades K-12, operated
      by the LAUSD. PARTICIPANTS: The LAUSD Food Services Branch, which serves about
      650 000 meals per day. INTERVENTION: A multistage menu planning approach that
      focused on implementing evidence-based strategies to improve the nutritional
      content of school breakfast and lunch menus. Engagement and formation of
      multisectoral partnerships, including public health and parent/student groups,
      were vital elements of the intervention process. MAIN OUTCOME MEASURE(S): Sodium
      content changes in the LAUSD menu, SY 2010-2011 versus SY 2011-2012; other
      measures include documentation of program reach. RESULTS: From SY 2010-2011 to SY
      2011-2012, the mean unweighted sodium levels for elementary (K-5) breakfast and
      for secondary (6-12) breakfast and lunch decreased. These changes met or exceeded
      the 2014-2015 US Department of Agriculture sodium targets for school meals and
      for secondary breakfast, the 2022-2023 target(s). These results, however, were
      not as notable once student food selection patterns (weighted data) and
      condiments were considered in the analysis. CONCLUSIONS: Use of strategy-focused
      menu planning as a mechanism to reduce sodium in school meals appeared to be
      promising, demonstrating favorable declines in mean sodium levels for at least 3
      of 4 meal categories in the LAUSD. Student food selection patterns and condiments
      use, however, can affect the strength of the intervention.

PMID- 24322816
TI  - Working with grocers to reduce dietary sodium: lessons learned from the Broome
      County Sodium Reduction in Communities pilot project.
AB  - The purpose of this article is to describe implementation of and lessons learned
      from the Broome County Sodium Reduction in Communities grocery store initiative.
      This pilot project was conducted in collaboration with a regional supermarket
      chain and endeavored to develop population-based strategies for reducing sodium
      intake. Key interventions included marketing strategies, taste test
      demonstrations, and a public media campaign. Project staff worked closely with
      corporate registered dietitian nutritionists, a nutrition specialist, and an
      advertising agency in its development and implementation. A social marketing
      approach was used to educate consumers about the hidden sources of dietary
      sodium, to raise awareness of the adverse health effects of excess sodium intake,
      to encourage consumers to read food labels, and to urge them to purchase food
      items lower in sodium. The lessons learned from this experience may be of
      assistance to other communities that seek to implement similar sodium-reduction
      strategies in the grocery store environment. 

PMID- 24322817
TI  - Beyond the clinic: importance of community involvement in sodium-reduction
      efforts.
AB  - Excessive sodium intake is a serious public health problem that is amenable to
      intervention. Despite campaigns that often target individuals to encourage lower
      sodium intake, consumption is far in excess of recommendations. There is
      increasing recognition of the importance of the food environment in shaping
      dietary behavior and the need for strategies that focus on changing community
      level environmental factors that support a shift in behavior toward more
      healthful eating. Practice-based evidence should be coupled with evidence from
      well-conducted clinical studies of sodium and health to build the foundation for
      public health interventions that achieve and sustain sodium reduction in the
      general population. This article discusses the importance of moving beyond the
      clinic and engaging communities in this important public health effort. 

PMID- 24322818
TI  - Sodium reduction in communities Shawnee County survey 2011: methods and baseline
      key findings.
AB  - CONTEXT: Hypertension is a major risk factor for cardiovascular disease and
      contributes to nearly half of all cardiovascular disease-related deaths in the
      United States. Even small reductions in sodium intake may lower blood pressure,
      help prevent the onset of hypertension, or help control blood pressure among
      hypertensive adults. Current nationally recommended strategies to reduce sodium
      intake include increasing public awareness about the amount of sodium added to
      processed and packaged foods and the health outcomes of a high-sodium diet.
      OBJECTIVE: To assess knowledge and behaviors related to sodium consumption among
      Shawnee County, Kansas, adults. DESIGN: Multicomponent survey, including random
      digit-dialed landline telephone interview, clinic-measured blood pressure, and a
      24-hour dietary recall, conducted during April-November 2011. SETTING AND
      PARTICIPANTS: Population-based sample of noninstitutionalized adults 18 years and
      older living in households with landline telephones in Shawnee County, Kansas.
      MAIN OUTCOME MEASURES: Knowledge about food sources of sodium and the link
      between sodium intake and hypertension; consumption of foods away from home and
      selected high-sodium foods; and addition of salt to foods. RESULTS: Eighty-three
      percent of adults strongly agreed or agreed that most of the sodium we eat comes
      from packaged, processed, store-bought, and restaurant foods, and 93.0% thought
      that a high-salt diet could cause hypertension. Adults ate slightly more than 3
      meals prepared outside the home per week, on average, and 1 in 4 adults added
      salt very often in cooking or preparing meals. Mean sodium intake among Shawnee
      County adults was 3508 mg per day. CONCLUSION: Despite extensive knowledge
      regarding food sources of sodium and the link between sodium intake and high
      blood pressure, mean sodium intake among Shawnee County adults exceeds current
      recommendations. The Shawnee County Sodium Reduction in Communities Program is
      currently implementing interventions that support access to and availability of
      lower-sodium options in Shawnee County.

PMID- 24322820
TI  - Different neural capacity limitations for articulatory and non-articulatory
      maintenance of verbal information.
AB  - Many studies have demonstrated attenuated verbal working memory (WM) under
      articulatory suppression. However, performance is not completely abolished,
      suggesting a less efficient, non-articulatory mechanism for the maintenance of
      verbal information. The neural causes for the reduced efficiency of such a
      putative complementary maintenance system have not yet been addressed. The
      present study was conducted to fill this gap. Subjects performed a Sternberg task
      (a) under articulatory maintenance at low, high, and supracapacity set sizes and
      (b) under non-articulatory maintenance at low and high set sizes. With functional
      magnetic resonance imaging, set-size related increases in activity were compared
      between subvocal articulatory rehearsal and non-articulatory maintenance. First,
      the results replicate previous findings showing different networks underlying
      these two maintenance strategies. Second, activation of all key nodes of the
      articulatory maintenance network increased with the amount of memorized
      information, showing no plateau at high set sizes. In contrast, for non
      articulatory maintenance, there was evidence for a plateau at high set sizes in
      all relevant areas of the network. Third, for articulatory maintenance, the non
      articulatory maintenance network was additionally recruited at supracapacity set
      sizes, presumably to assist processing in this highly demanding condition. This
      is the first demonstration of differential neural bottlenecks for articulatory
      and non-articulatory maintenance. This study adds to our understanding of the
      performance differences between these two strategies supporting verbal WM. 

PMID- 24322821
TI  - Sleep enhances inhibitory behavioral control in discrimination learning in rats.
AB  - Sleep supports the consolidation of memory, and it has been proposed that this
      enhancing effect of sleep pertains in particular to memories which are encoded
      under control of prefrontal-hippocampal circuitry into an episodic memory system.
      Furthermore, repeated reactivation and transformation of such memories during
      sleep are thought to promote the de-contextualization of these memories. Here, we
      aimed to establish a behavioral model for the study of such sleep-dependent
      system consolidation in rats, using a go/nogo conditional discrimination learning
      task known to essentially depend on prefrontal-hippocampal function. Different
      groups of rats were trained to criterion on this task and, then, subjected to 80
      min retention intervals filled with spontaneous morning sleep, sleep deprivation,
      or spontaneous evening wakefulness. In a subsequent test phase, the speed of
      relearning of the discrimination task was examined as indicator of memory,
      whereby rats were either tested in the same context as during training or in a
      different context. Sleep promoted relearning of the conditional discrimination
      task, and this effect was similar for testing memory in the same or different
      context (p < 0.001). Independent of sleep and wakefulness during the retention
      interval, animals showed faster relearning when tested in the same context as
      during learning, compared with testing in a different context (p < 0.001). The
      benefitting effect of sleep on discrimination learning was primarily due to an
      enhancing effect on response suppression during the nogo stimulus. We infer from
      these results that sleep enhances memory for inhibitory behavioral control in a
      generalized context-independent manner and thereby might eventually also
      contribute to the abstraction of schema-like representations.

PMID- 24322823
TI  - Facing a patient who seeks help after a suicide attempt: the difficulties of
      health professionals.
AB  - BACKGROUND: Although intervention with suicidal patients is one of the hardest
      tasks in clinical practice, little is known about health professionals'
      perceptions about the difficulties of working with suicidal patients. AIMS: The
      aims of this study were to: (1) describe the difficulties of professionals facing
      a suicidal patient; (2) analyze the differences in difficulties according to the
      sociodemographic and professional characteristics of the health professionals;
      and (3) identify the health professionals' perceived skills and thoughts on the
      need for training in suicide. METHOD: A self-report questionnaire developed for
      this purpose was filled out by 196 health professionals. Exploratory principal
      components analyses were used. RESULTS: Four factors were found: technical
      difficulties; emotional difficulties; relational and communicational
      difficulties; and family-approaching and logistic difficulties. Differences were
      found between professionals who had or did not have training in suicide, between
      professional groups, and between the number of patient suicide attempts. Sixty
      percent of the participants reported a personal need for training and 85% thought
      it was fundamental to implement training plans targeted at health professionals.
      CONCLUSION: Specific training is fundamental. Experiential and active
      methodologies should be used and technical, relational, and emotional questions
      must be included in the training syllabus.

PMID- 24322822
TI  - Levetiracetam results in increased and decreased alcohol drinking with different
      access procedures in C57BL/6J mice.
AB  - The antiepileptic levetiracetam (LEV) has been investigated for the treatment of
      alcohol abuse. However, little is known about how LEV alters the behavioral
      effects of alcohol in laboratory animals. The acute effects of LEV on alcohol
      drinking by male C57BL/6J mice were investigated using two different drinking
      procedures, limited access [drinking-in-the-dark (DID)] and intermittent access
      (IA) drinking. In the first experiment (DID), mice had access to a single bottle
      containing alcohol or sucrose for 4 h every other day. In the second experiment
      (IA), mice had IA to two bottles, one containing alcohol or sucrose and one
      containing water, for 24 h on Monday, Wednesday, and Friday. In both experiments,
      mice were administered LEV (0.3-100 mg/kg intraperitoneally) or vehicle 30 min
      before access to the drinking solutions. In the DID mice, LEV increased alcohol
      intake from 4.3 to 5.4 g/kg, whereas in the IA mice LEV decreased alcohol intake
      from 4.8 to 3.0 g/kg in the first 4 h of access and decreased 24 h alcohol intake
      from 20 to ~15 g/kg. These effects appear specific to alcohol, as LEV did not
      affect sucrose intake in either experiment. LEV appears to differentially affect
      drinking in animal models of moderate and heavier alcohol consumption. 

PMID- 24322824
TI  - Why do we report suicides and how can we facilitate suicide prevention efforts?
      Perspectives of Hong Kong media professionals.
AB  - BACKGROUND: The Hong Kong news media report suicide-related events more
      frequently and sensationally than Western countries. Little is known about Hong
      Kong media professionals' experiences and thoughts about such reporting. AIMS: To
      understand Hong Kong media professionals' experiences and perceptions of suicide
      reporting and whether the news media can be better engaged into suicide
      prevention. METHOD: We conducted three focus groups of journalists from both the
      Cantonese and English language news media. Data were analyzed using grounded
      theory methods. RESULTS: We discerned three rationales from participants
      regarding their intense coverage of suicide-related events: (1) satisfying
      commercial competitiveness, (2) addressing social problems, and (3) responding to
      readers' interests. The first rationale was a dominant and vigorous motivating
      factor, and often influenced suicide reporting among local Cantonese media. Media
      professionals recommended engagement strategies targeted at frontline
      journalists, media managers, and general media consumers. CONCLUSION: We see
      potential to involve news media professionals in Hong Kong as working partners in
      suicide prevention. To succeed, this effort requires engagement in a proactive,
      consistent, and sustained fashion.

PMID- 24322825
TI  - Predictors of having paid work in older workers with and without chronic disease:
      a 3-year prospective cohort study.
AB  - BACKGROUND: As the prevalence of chronic disease amongst older workers is high
      and increasing, it is important to know if the large subgroup of older workers
      with chronic disease has specific needs when it comes to prolonging participation
      in paid work. OBJECTIVES: To investigate differences and similarities in
      predictors of having paid work in workers aged 55+ with and without chronic
      disease. METHODS: Workers aged 55-62 years were selected from the 2002-2003
      cohort of the Longitudinal Aging Study Amsterdam (n = 333). Potential predictors
      were: health, personality, work characteristics, and demographics. Per potential
      predictor, a logistic regression coefficient for 'having paid work in 2005-2006'
      was calculated for workers with and without chronic disease. A pooled estimate
      was computed and differences between the pooled estimate and the coefficients
      were tested. Results Follow-up data were available for 95 %, of whom 67 % still
      had paid work. Predictors of having paid work were similar for workers with and
      without chronic diseases, except for physical workload (chi(2) = 5.37; DF = 1)
      and psychosocial resources at work (chi(2) = 5.94; DF = 1). Having more
      psychosocial resources (OR = 3.57; 95 %CI 1.33-10.0) was predictive for having
      paid work in workers with chronic disease and not in workers without chronic
      disease. Lower age, more weekly working hours, no functional limitations, fewer
      depressive symptoms, lower neuroticism scores, and more sense of mastery were
      significantly associated with having paid work in all workers. CONCLUSIONS:
      Differences between predictors of having paid work between workers with and
      without chronic disease should be taken into account when aiming to prevent exit
      from the workforce. In particular the vulnerable subgroup of older workers with
      chronic disease and low psychosocial resources at work is more likely to quit
      working.

PMID- 24322826
TI  - The risk of skin cancer in psoriasis patients treated with UVB therapy.
AB  - Phototherapy is an effective and widely used treatment for generalised plaque
      psoriasis. Despite the mutagenic effects of UVB this type of therapy is still
      assumed to be a safe treatment option. We have performed a cross sectional study
      to assess the risk of skin cancer in the cohort of psoriasis patients treated
      with UVB. A total of 162 white patients (116 men and 46 women, mean +/- standard
      deviation age 56.0 +/- 13.5 years) were included in the study. All patients have
      previously been treated with UVB at least 100 times in the last 5 years. Eight
      patients (4.9%, 0.95 CI: 2.2-9.5%) out of the 162 included in the study had
      histopathologically verified skin cancer. We found that the risk of skin cancer
      in psoriasis patients treated with UVB correlated with the number of treatments
      (controlling for age) but not with the type of UVB lamp. How-ever, the overall
      risk of malignancy in the UVB-treated patients was not greater than in the
      general population.

PMID- 24322828
TI  - Vapochemically and mechanochemically reversible polymerization/depolymerization
      of S-Fe-Cu carbonyl clusters.
AB  - A reversible vapochemical and mechanochemical solid-state transformation between
      a dppe-linked SFe3Cu2-based cluster [{(MU3-S)Fe3(CO)9}Cu2(dppe)] (2) and its 1D
      polymer [{(MU4-S)Fe3(CO)9}Cu2(dppe)(MeCN)2]n (3) was demonstrated, in which
      polymer 3 exhibited semi-conducting properties with an energy gap of 1.69 eV.

PMID- 24322827
TI  - How does experience modulate auditory spatial processing in individuals with
      blindness?
AB  - Comparing early- and late-onset blindness in individuals offers a unique model
      for studying the influence of visual experience on neural processing. This study
      investigated how prior visual experience would modulate auditory spatial
      processing among blind individuals. BOLD responses of early- and late-onset blind
      participants were captured while performing a sound localization task. The task
      required participants to listen to novel "Bat-ears" sounds, analyze the spatial
      information embedded in the sounds, and specify out of 15 locations where the
      sound would have been emitted. In addition to sound localization, participants
      were assessed on visuospatial working memory and general intellectual abilities.
      The results revealed common increases in BOLD responses in the middle occipital
      gyrus, superior frontal gyrus, precuneus, and precentral gyrus during sound
      localization for both groups. Between-group dissociations, however, were found in
      the right middle occipital gyrus and left superior frontal gyrus. The BOLD
      responses in the left superior frontal gyrus were significantly correlated with
      accuracy on sound localization and visuospatial working memory abilities among
      the late-onset blind participants. In contrast, the accuracy on sound
      localization only correlated with BOLD responses in the right middle occipital
      gyrus among the early-onset counterpart. The findings support the notion that
      early-onset blind individuals rely more on the occipital areas as a result of
      cross-modal plasticity for auditory spatial processing, while late-onset blind
      individuals rely more on the prefrontal areas which subserve visuospatial working
      memory. 

PMID- 24322829
TI  - Human fronto-parietal and parieto-hippocampal pathways represent behavioral
      priorities in multiple spatial reference frames.
AB  - We represent behaviorally relevant information in different spatial reference
      frames in order to interact effectively with our environment. For example, we
      need an egocentric (e.g., body-centered) reference frame to specify limb
      movements and an allocentric (e.g., world-centered) reference frame to navigate
      from one location to another. Posterior parietal cortex (PPC) is vital for
      performing transformations between these different coordinate systems. Here, we
      review evidence for multiple pathways in the human brain, from PPC to motor,
      premotor, and supplementary motor areas, as well as to structures in the medial
      temporal lobe. These connections are important for transformations between
      egocentric reference frames to facilitate sensory-guided action, or from
      egocentric to allocentric reference frames to facilitate spatial navigation. 

PMID- 24322830
TI  - Association of thiopurine methyltransferase status with azathioprine side effects
      in Chinese patients with systemic lupus erythematosus.
AB  - Azathioprine (AZA) is indicated for the treatment of systemic lupus erythematosus
      (SLE). Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in the
      steps of AZA metabolization. Heritable deficiency of TPMT enzyme activity and
      polymorphisms may lead to leukopenia. This study aims to detect TPMT
      polymorphisms and TPMT enzyme activity in Chinese SLE patients and to describe
      the association between TPMT genotypes and adverse effects of AZA. One hundred
      and twenty-six SLE patients with present or previous thiopurine therapy were
      identified from a local database. Adverse effects were documented. No TPMT*2,
      TPMT*3A, or TPMT*3B mutant alleles were detected. TPMT*3C was detected in four
      patients (3.17 %). The heterozygotes had significantly lower mean TPMT activity
      as compared to the homozygotes (2.38 +/- 1.24 vs. 12.56 +/- 7.02 U/mL, P <
      0.001). Twenty-seven cases (21.42 %) exhibited adverse effects. All of the
      heterozygotes (4/4, 100 %) developed severe leukopenia, and three cases (3/4, 75
      %) of whom exhibited alopecia simultaneously. The specificity of TPMT*3C for
      predicting leukopenia and alopecia was 100 and 99.17 %, respectively, and the
      sensitivity was 28.57 and 60.00 %, respectively. The mean value of TPMT activity
      with leukopenia (4.67 +/- 3.01 vs. 13.2 +/- 6.94 U/mL RBC, P < 0.001) or alopecia
      (2.31 +/- 1.16 vs. 12.65 +/- 6.98 U/mL RBC, P < 0.001) was significantly lower
      than those without. TPMT*3C was the most common mutant polymorphism found in the
      study group. TPMT activity is reduced in TPMT*3C mutant. AZA-induced leukopenia
      and alopecia were partly correlated to TPMT*3C heterozygotes and low TPMT
      activity. The results of this study suggest that the value of TPMT genotyping
      before AZA therapy was limited in Chinese SLE patients, considering the low
      sensitivity. Routine monitoring of TPMT activity before prescribing and
      continuous hematological monitoring dose were recommended. 

PMID- 24322831
TI  - Single center study on ethnic and clinical features of Behcet's disease in
      Moscow, Russia.
AB  - For the purpose of investigating Behcet's disease (BD) in Russia, 250 consecutive
      patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the
      Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow
      were enrolled in this study. The ethnic backgrounds of the patients were reported
      as follows: 23.2% (58 cases) from Russia, 12.8% (32 cases) from Azerbaijan, 14.4%
      (36 cases) from Armenia, 8.8% (22 cases) from Chechnya, and 21.6% (55 cases) from
      Dagestan. The remaining 19.2% (48 cases) were from other regions or of unknown
      origin. More than half (57.6%) of the Behcet's disease patients originated from
      Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean
      age at disease onset was 31.5 +/- 9.38 (13-60) years old, and the most typical
      initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old
      were more commonly affected and displayed a wide clinical spectrum of the
      disease, with varieties of severe internal organ involvement. The manifestations
      observed throughout the course of the disease included oral aphthous ulcers
      (100%), various cutaneous lesions (88.8%), genital ulcers (81.2%), and ocular
      lesions (54.0%). Besides these, many organs/systems were implicated in patient
      cases, namely joint (53.2%), vascular (25.2%), neurological (8.0%),
      gastrointestinal (25.2%), and cardiac (5.6%) systems. Involvements of ocular (p <
      0.01) and skin (p < 0.01) lesions were more frequent in men than in women. HLA
      B51 and HLA-A26 typing was performed in 127 patients and 508 healthy controls.
      HLA-B51 was found in 63.0% of BD patients compared to 20.7% of the healthy
      control subjects (p < 0.001), and HLA-A26 was present in 11.3% of BD patients and
      18.9% of the control group. This study shows the presence of BD in Russia, and it
      is suggested that its prevalence in Central Asian people is much higher than that
      in White Russian.

PMID- 24322832
TI  - Fatigue in patients with spondyloarthritis associates with disease activity,
      quality of life and inflammatory bowel symptoms.
AB  - The study aimed to assess the severity of fatigue in patients with axial
      spondyloarthritis (AxSpA), to assess the performance of two different fatigue
      measures in AxSpA, and to examine disease variables which may influence the
      severity of fatigue. Fatigue was examined among 67 patients with AxSpA using two
      measures: the fatigue Visual Analogue Scale (VAS) from the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) and the Multidimensional Assessment
      of Fatigue (MAF) score. These measures were tested for convergent validity using
      linear regression analysis. Correlations between fatigue measured using both
      questionnaires, and key disease variables was examined using the following
      assessments: BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI),
      Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, spondyloarthritis
      modification of the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ) and
      pain VAS. Human leucocyte antigen (HLA) B27 and CRP were performed and followed
      by physical examination, Bath AS Metrology Index (BASMI) and Ankylosing
      Spondylitis Disease Activity Score (ASDAS). Correlations were assessed using
      multivariate regression analysis. Mean (+/-SD) fatigue measured by MAF (range 0
      50) was 24.7 (+/-11.5) and 5.14 (+/-2.47) on the BASDAI VAS fatigue item (range 0
      10). The MAF scores and BASDAI VAS fatigue were strongly correlated (r = 0.71, P
      < 0.001), but 50 % of variance remained unexplained, so both were retained as
      separate variables in bivariate and multivariate analyses. In multivariate
      regression models, a significant relationship for both fatigue measures was
      consistently noted with DISQ bowel symptom scores. MAF fatigue scores were most
      strongly associated with poorer ASQoL in multivariate models and mediated the
      effects of BASFI functioning, ASDAS disease activity and HLA-B27 status that were
      apparent in multivariate models. Patients with AxSpA experience substantial
      fatigue, which is associated with poorer quality of life. Fatigue VAS and MAF
      scores were strongly correlated. Factors most strongly associated with fatigue
      were disease activity and inflammatory bowel symptoms.

PMID- 24322833
TI  - Cartilage signal intensity on T1-weighted MRI: association with risk factors and
      measures of knee osteoarthritis.
AB  - This study aims to assess mean signal intensity of cartilage on T1-weighted
      magnetic resonance imaging (MRI) images, and then examine whether mean signal
      intensity is associated with risk factors and measures of osteoarthritis in
      younger and older adults. A total of 50 younger adult subjects (mean age 41,
      range 29-57; 64% female; baseline only) and 168 older adult subjects (mean age
      63, range 52-78; 46% female; baseline and 2.9 year followup) were randomly
      selected from the community. T1-weighted fat-supressed gradient recall echo MRI
      scans of right knees were performed. Image segmentation was performed semi
      automatically, and measures of mean signal intensity and cartilage thickness for
      regions of cartilage were obtained. Urinary levels of C-terminal crosslinking
      telopeptide of type II collagen (U-CTX-II) were measured in younger adults.
      Cartilage defects were scored using a 5-point scale in both groups. In
      multivariable analyses, higher cartilage defects and BMI were significantly
      associated with lower same-region mean signal intensity in younger and older
      adults. CTX-II was negatively and significantly associated with mean signal
      intensity of cartilage in the lateral femoral and patellar sites. Joint space
      narrowing and osteophytes analysed in older adults were significantly associated
      with reduced mean signal intensity at various sites. Over 2.9 years, lower mean
      signal intensity at femoral and patellar sites and in whole knee was associated
      with decreases in cartilage thickness. Reduced mean signal intensity of cartilage
      on T1-weighted gradient recall echo MRI is associated with osteoarthritis risk
      factors and predicts cartilage loss suggesting low cartilage signal intensity may
      reflect early osteoarthritic changes.

PMID- 24322834
TI  - The 2013 American Association of Clinical Endocrinologists' diabetes mellitus
      management recommendations: improvements needed.

PMID- 24322836
TI  - Chemical composition tuning in quaternary p-type Pb-chalcogenides--a promising
      strategy for enhanced thermoelectric performance.
AB  - Recently a significant improvement in the thermoelectric performance of p-type
      ternary PbTe-PbSe and PbTe-PbS systems has been realized through alternating the
      electronic band structure and introducing nano-scale precipitates to bulk
      materials respectively. However, the quaternary system of PbTe-PbSe-PbS has
      received less attention. In the current work, we have excluded phase complexity
      by fabricating single phase sodium doped PbTe, alloyed with PbS up to its
      solubility limit which is extended to larger concentrations than in the ternary
      system of PbTe-PbS due to the presence of PbSe. We have presented a
      thermoelectric efficiency of approximately 1.6 which is superior to ternary PbTe
      PbSe and PbTe-PbS at similar carrier concentrations and the binary PbTe, PbSe and
      PbS alloys. The quaternary system shows a larger Seebeck coefficient than the
      ternary PbTe-PbSe alloy, indicative of a wider band gap, valence band energy
      offset and heavier carriers effective mass. In addition, the existence of PbS in
      the alloy further reduces the lattice thermal conductivity originated from phonon
      scattering on solute atoms with high contrast atomic mass. Single phase
      quaternary PbTe-PbSe-PbS alloys are promising thermoelectric materials that
      provide high performance through adjusting the electronic band structure by
      regulating chemical composition. 

PMID- 24322835
TI  - Determinants of the transition from a cardiometabolic normal to abnormal
      overweight/obese phenotype in a Spanish population.
AB  - PURPOSE: There is limited prospective evidence at population scale of the impacts
      of lifestyle and surrogate measures of general and abdominal adiposity on the
      transition of a metabolically healthy (absence of a metabolic disorder)
      overweight/obese (MHOO) phenotype to a metabolically abnormal overweight/obese
      (MAOO) phenotype. Therefore, we determined the relationship between 10-year body
      mass index (BMI), waist circumferences (WC), waist to height ratio (WHtR), and
      lifestyle changes and the transition of the MHOO phenotype. METHODS: We conducted
      a prospective population-based study of 3,052 male and female Spaniards aged 25
      74 years who were followed from 2000 through 2009. Diet and leisure-time physical
      activity were recorded on validated questionnaires. Weight, height, WC, blood
      lipids, glycemia, and blood pressure were measured. All variables were obtained
      at baseline (BL) and follow-up (FL). Participants with a BMI >= 25 kg/m(2) and
      free from hypercholesterolemia, hypertriglyceridemia, diabetes, hypertension, and
      low HDL and high LDL cholesterol levels were characterized as the MHOO phenotype.
      A composite healthy lifestyle index (HLI) was constructed by including temporary
      changes in 3 lifestyle variables (diet, leisure-time physical activity, and
      smoking). RESULTS: Initially, 20.8% of subjects had the MHOO phenotype; 49.2% of
      these shifted to MAOO phenotype. In multivariate analysis, changes in BMI, WC,
      WHtR were positively associated (p = 0.004, p = 0.018, and p = 0.016,
      respectively) with this transition. One unit increase in the HLI was associated
      with a 33% lower risk (p = 0.025) to the MAOO phenotype transition after
      adjusting for age, sex, educational level, and baseline energy intake, BMI, WC,
      and WHtR. CONCLUSIONS: The presence of metabolic disorders in the MHOO phenotype
      is predicted by an increase in anthropometric surrogate measures of general and
      abdominal adiposity. In contrast, a healthy lifestyle protects against a
      transition to the MAOO phenotype.

PMID- 24322837
TI  - Tobacco smoking cessation and improved gastroesophageal reflux: a prospective
      population-based cohort study: the HUNT study.
AB  - OBJECTIVES: Tobacco smoking increases the risk of gastroesophageal reflux
      symptoms (GERS), but whether tobacco smoking cessation improves GERS is unclear.
      The aim of this study was to clarify if tobacco smoking cessation improves GERS.
      METHODS: The study was based on the Nord-Trondelag health study (the HUNT study),
      a prospective population-based cohort study conducted from 1995-1997 to 2006-2009
      in Nord-Trondelag County, Norway. All residents of the county from 20 years of
      age were invited. The study included 29,610 individuals (61% response rate) who
      reported whether they had heartburn or acid regurgitation. The association
      between tobacco smoking cessation and improvement in GERS was assessed by
      logistic regression, providing odds ratios (ORs) with 95% confidence intervals
      (CIs). The analyses were stratified by antireflux medication, and the results
      were adjusted for sex, age, body mass index (BMI), alcohol consumption,
      education, and physical exercise. Subgroup analyses were also stratified by BMI.
      RESULTS: Among individuals using antireflux medication at least weekly, cessation
      of daily tobacco smoking was associated with improvement in GERS from severe to
      no or minor complaints (adjusted OR 1.78; 95% CI: 1.07-2.97), compared with
      persistent daily smoking. This association was present among individuals within
      the normal range of BMI (OR 5.67; 95% CI: 1.36-23.64), but not among overweight
      individuals. There was no association between tobacco smoking cessation and GERS
      status among individuals with minor GERS or individuals using antireflux
      medication less than weekly. CONCLUSIONS: Tobacco smoking cessation was
      associated with improvement in severe GERS only in individuals of normal BMI
      using antireflux medication at least weekly, but not in other individual with
      GERS.

PMID- 24322838
TI  - Necroptosis is active in children with inflammatory bowel disease and contributes
      to heighten intestinal inflammation.
AB  - OBJECTIVES: A new caspase-independent mode of programmed cell death, termed
      necroptosis, has recently been identified. Altered expression of molecules
      involved in the necroptosis pathway has been shown to trigger intestinal
      inflammation. The initiation of necroptosis is principally mediated by the
      release of receptor interacting protein 3 (RIP3) from suppression by caspase-8.
      Furthermore, it has been suggested that the mixed lineage kinase domain-like
      (MLKL) factor is an interacting target of RIP3 in active necroptosis. This study
      aims at investigating the occurrence of necroptosis in children with inflammatory
      bowel disease (IBD) and its contribution to human intestinal inflammation.
      METHODS: Biopsy samples were collected from the ileum and colon of 33 children
      with Crohn's disease, 30 with ulcerative colitis, and 20 healthy controls. Ten
      children with allergic colitis (AC) were used as non-IBD comparators. RIP3,
      caspase-8, and MLKL protein expression levels were evaluated by western blotting.
      The adenocarcinoma cell line HT29 was used for in vitro experiments. RESULTS:
      RIP3 and MLKL increased (P<0.01) in inflamed tissues of IBD and AC patients,
      whereas caspase-8 was reduced. No variations were observed in uninflamed tissues
      of patients. The relationship between RIP3 increase, active necroptosis, and
      intestinal inflammation was confirmed by in vitro analyses. CONCLUSIONS: We show
      for the first time that necroptosis is strongly associated with intestinal
      inflammation in children with IBD and contributes to strengthen the inflammatory
      process. We believe that RIP3 and MLKL could represent attractive targets for the
      management of human IBD.

PMID- 24322839
TI  - The role of thiopurines in reducing the need for surgical resection in Crohn's
      disease: a systematic review and meta-analysis.
AB  - OBJECTIVES: The thiopurine (TP) analogs azathioprine and mercaptopurine have
      proven efficacy in inducing and maintaining clinical remission in Crohn's disease
      (CD). Their impact on the long-term need for surgery is uncertain since studies
      have reported conflicting results. The aim of this systematic review was to
      summarize and evaluate evidence of the published literature regarding those
      studies assessing the impact of TPs on the risk of first surgical resection in
      CD. METHODS: We searched Medline, EMBASE, CINAHL, and hand searched reference
      lists of identified articles, without language restrictions in August 2013.
      RESULTS: Seventeen retrospective observational studies (eight population based,
      three multicenter, and six referral center) representing 21,632 participants met
      our inclusion criteria. Of these 10 studies involving 12,586 participants
      provided data on the hazard ratio (HR) and 95% confidence intervals (CIs)
      evaluating use of TPs and surgical risk. The combined pooled HR of first
      intestinal resection with TP use was 0.59 (95% CI 0.48-0.73). CONCLUSIONS: TP use
      is associated with a 40% lowered risk of surgical resection in patients with CD.
      Despite significant reductions in rates of surgical resection in patients with CD
      over the last 5 decades and increasing use of TPs, a large proportion of patients
      with CD still require resectional surgery.

PMID- 24322840
TI  - Elective medical and veterinary student rotations in applied epidemiology at the
      Centers for Disease Control and Prevention, 1975-2012.
AB  - CONTEXT: Health professionals who can bridge the gap between public health and
      clinical medicine are needed. The Centers for Disease Control and Prevention
      Epidemiology Elective Program (EEP) offers a rotation in public health for
      medical and veterinary students that provides an introduction to public health,
      preventive medicine, and the principles of applied epidemiology through real
      world, hands-on experiential learning. OBJECTIVE: To describe EEP, including its
      role in the integration of medicine and public health, and career paths for those
      who subsequently have enrolled in the Epidemic Intelligence Service (EIS).
      DESIGN: A review of files of EEP students participating June 1975 to May 2012 and
      EIS files to determine which EEP participants subsequently enrolled in EIS and
      their current employment. RESULTS: During January 1975 to May 2012, a total of
      1548 students participated in EEP. Six hundred thirty-eight (41.2%) EEP students
      participated in field-based epidemic-assistance investigations. Among 187
      students completing an exit survey implemented during 2007, a total of 175
      (93.6%) indicated an increased understanding or competence in applied
      epidemiology and public health, and 98 (52.4%) indicated that they would apply to
      EIS. Among the 165 (10.7%) who enrolled in and completed EIS by July 2012, 106
      (64.2%) are currently employed in public health and 65 (39.4%) are board
      certified in preventive medicine, board eligible, or currently enrolled in the
      Centers for Disease Control and Prevention Preventive Medicine Residency or
      Fellowship. CONCLUSIONS: The CDC Epidemiology Elective Program offers
      opportunities for medical and veterinary students to participate in real-world
      public health learning activities. The Epidemiology Elective Program provides
      increased understanding and competence in applied epidemiology, provides students
      with opportunities to learn about population health and health care problems and
      the tools to help them bridge the gap between clinical medicine and public
      health, and serves as a source for EIS and other public health-related training
      and careers.

PMID- 24322841
TI  - Teaching health advocacy to medical students: a comparison study.
AB  - CONTEXT: Many encourage service learning and health advocacy training in medical
      student education, but related evaluation is limited. OBJECTIVES: To assess (1)
      impact of a required community health advocacy training for medical students on
      student attitudes, knowledge, and skills; (2) student characteristics associated
      with higher advocacy knowledge and skills; and (3) perspectives of community
      based organizations (CBOs). DESIGN: Cross-sectional surveys. SETTING: University
      of Miami Miller School of Medicine (UMMSM) Regional Medical Campus and main
      campus. PARTICIPANTS: Medical students at both UMMSM campuses. INTERVENTION:
      Required community health advocacy training for first- and second-year students
      including classroom experiences and hands-on project in partnership with a CBO.
      MAIN OUTCOME MEASURES: Student characteristics, health advocacy-related
      attitudes, self-reported and objective knowledge, and skills. Scores were
      compared between campuses, with multivariable modeling adjusting for individual
      student characteristics. Community-based organization perspectives were assessed
      via separate surveys. RESULTS: Ninety-eight (77%) regional campus students
      (intervention group) and 139 (30%) main campus students (comparison group)
      completed surveys. Versus the comparison group, the intervention group reported
      greater: mean knowledge of community health needs: 34.6 versus 31.1 (range: 11
      44, P < .01), knowledge about CBOs: 3.0 versus 2.7 (range 1-4, P < .01) and
      knowledge of community resources: 5.4 versus 2.3 (range, 0-11, P < .01), and mean
      skill scores: 12.7 versus 10.5 (score range: 4-16, P < .01), following the
      intervention. Using adjusted analysis across both groups, female gender was
      associated with higher attitudes score. High level of previous community
      involvement was associated with higher attitude and skill scores. Higher self
      reported educational debt was associated with higher skill scores. Community
      based organization perspectives included high satisfaction and a desire to
      influence the training of future physicians. CONCLUSIONS: Medical student
      advocacy training in partnership with community-based organizations could be
      beneficial in improving student advocacy knowledge and skills in addressing
      community health issues and in developing sustainable community partnerships.

PMID- 24322843
TI  - Wave field sensing by means of computational shear interferometry.
AB  - In this paper, we present a method to recover the complex amplitude of speckle
      fields from measurements performed by a shear interferometer. It is based on the
      optimization of an objective function using the steepest descent gradient
      technique in combination with a heuristic initial guess. In contrast to already
      existing methods, the algorithm finds a local minimum least-squares solution even
      in the presence of Poissonian and Gaussian noise. 

PMID- 24322842
TI  - Conceptualizing and measuring community preparedness within public health
      preparedness and response: complexities and lessons learned.
AB  - Since 2001, the Centers for Disease Control and Prevention's Public Health
      Emergency Preparedness cooperative agreement has supported state, territorial,
      and local public health departments in preparing for and responding to public
      health emergencies. This conceptual article describes complexities identified and
      lessons learned in developing community preparedness performance measures for the
      Centers for Disease Control and Prevention's public health preparedness program.
      Challenges arose in (a) defining community; (b) measuring meaningful community
      engagement; and (c) determining a strategy for collecting, aggregating, and
      analyzing data from diverse state, territorial, and local health departments.
      This article contributes to prior work describing conceptual challenges in
      developing standardized measures of performance at the federal level and suggests
      ways to potentially mitigate general performance measurement challenges as well
      as measurement complexities specific to community preparedness. It may be
      informative for those state, territorial, and local health departments currently
      implementing (or contemplating implementing) community preparedness activities
      and for individuals more generally engaged in performance measurement.

PMID- 24322844
TI  - Scattering of a zero-order Bessel beam by arbitrarily shaped homogeneous
      dielectric particles.
AB  - In this paper, we introduce an efficient numerical method based on surface
      integral equations to characterize the scattering of a zero-order Bessel beam by
      arbitrarily shaped homogeneous dielectric particles. The incident beam is
      described by vector expressions in terms of the electric and magnetic fields that
      perfectly satisfy Maxwell's equations. The scattering problems involving
      homogeneous dielectric particles with arbitrary shapes are formulated with the
      electric and magnetic current combined-field integral equation and modeled by
      using surface triangular patches. Solutions are performed iteratively by using
      the multilevel fast multipole algorithm. Some numerical results are included to
      illustrate the validity and capability of the proposed method. These results are
      also expected to provide useful insights into the scattering of a Bessel beam by
      complex-shaped particles. 

PMID- 24322845
TI  - Arbitrary interference curves by coincidence detection: theory and experiment.
AB  - We discuss how to use coincidence detection to generate unusual, nonsinusoidal
      interference curves by using not a single detector, but several in coincidence.
      The method works for both strong (classical) and weak (on the few-photon level)
      light, although in the latter case the detection becomes probabilistic with low
      efficiency. Using the method, one can tailor the coincidence measurement setup to
      obtain essentially any interference pattern. We then use the method to
      experimentally demonstrate phase-difference state interference patterns in the
      few-photon regime that are highly nonsinusoidal. We also discuss optimal
      implementation of the method with regard to fluctuations and success probability,
      and we analyze the origin and magnitude of errors. 

PMID- 24322846
TI  - Measurement of rod and cone effects in mesopic visual sensitivity by varying
      viewing field.
AB  - To investigate the effects of rods and cones in mesopic visual sensitivity, we
      perform spectral sensitivity experiments by varying viewing fields and adaptation
      levels. We obtain mesopic spectral sensitivities for 2 degrees  and 10 degrees 
      centrally viewing fields and a (10 degrees -20 degrees ) peripherally viewing
      field at adaptation luminance levels of 0.04 cd/m2, 0.4 cd/m2, and 1.8 cd/m2. The
      spectral shapes are examined through comparison with the Commission International
      de l'Eclairage luminous efficiency functions. We observe a decrease of visual
      sensitivity with an increase of adaptation luminance and the dependence of visual
      sensitivity on viewing field. The observation is discussed in terms of the
      interaction between rods and cones.

PMID- 24322847
TI  - Effect of polarization purity of cylindrical vector beam on tightly focused spot.
AB  - The tightly focused spots of cylindrical vectors (CVs) are dependent on
      polarization composition. We experimentally demonstrate the effect of
      polarization purity (PP) of the CV beam on the tightly focused spot
      quantitatively, which should be strictly controlled for the effective
      applications of the CV beam. The focal spots measured by a knife-edge scanning
      method showed that the azimuthally polarized (AP) component increases the
      transverse field and the size of the focal spots, while the radially polarized
      component results in a nonzero intensity distribution at the center of the focus
      even in a high PP AP beam. 

PMID- 24322848
TI  - On the perfectly matched layer and the DB boundary condition.
AB  - In this paper, we consider a particular uniaxial material able to achieve the DB
      boundary condition. We show how, for particular transverse electromagnetic
      properties, this material behaves like a perfectly matched layer (PML). Moreover,
      we find that, with an approximation, the material becomes passive, i.e., loses
      the active part of the permittivity and of the permeability typical of a PML. In
      this case, the uniaxial medium becomes realizable as a particular absorbing
      metamaterial. We present simulations with both guided and free-space waves to
      show the absorbing behavior of the proposed material. 

PMID- 24322849
TI  - Internal fields of soot fractal aggregates.
AB  - This work uses the discrete dipole approximation (DDA) to examine the internal
      electric field within a simulated carbon soot fractal aggregate in fixed and
      random orientations. For fixed orientations, deviations of the internal field
      magnitude up to +/-50% from that assumed by the Rayleigh-Debye-Gans Approximation
      (RDGA) are found. Given the refractive index of the aggregate monomers and
      conditions for the validity of the approximation, such large deviations are no
      surprise. Yet despite this deviation, the far-field scattered intensity from such
      aggregates agrees surprisingly well with that described by the RDGA. Moreover, if
      the average over an ensemble of many random aggregate-orientations is calculated,
      both the DDA and RDGA scattered intensities obey the well-known power-law
      functionality in terms of the scattering wave vector and show a forward-angle
      intensity-maximum proportional to the square of the number of monomers. The
      explanation for this lies in the over and under estimations made by the
      approximation of the internal field, which apparently mostly cancel upon
      integration to yield the scattered intensity. It is shown that this error
      cancellation is related to the fractal structure of the aggregate and that the
      agreement between the DDA and RDGA improves with aggregates of increasing size
      provided the fractal dimension is less than two. Overall, the analysis suggests
      that both the special fractal character of the aggregate and its orientational
      averaging is important to account for the experimentally observed validity of the
      RDGA despite its poor description of the internal fields. 

PMID- 24322850
TI  - High-order total variation-based multiplicative noise removal with spatially
      adapted parameter selection.
AB  - Multiplicative noise is one common type of noise in imaging science. For coherent
      image-acquisition systems, such as synthetic aperture radar, the observed images
      are often contaminated by multiplicative noise. Total variation (TV)
      regularization has been widely researched for multiplicative noise removal in the
      literature due to its edge-preserving feature. However, the TV-based solutions
      sometimes have an undesirable staircase artifact. In this paper, we propose a
      model to take advantage of the good nature of the TV norm and high-order TV norm
      to balance the edge and smoothness region. Besides, we adopt a spatially
      regularization parameter updating scheme. Numerical results illustrate the
      efficiency of our method in terms of the signal-to-noise ratio and structure
      similarity index. 

PMID- 24322851
TI  - Polarization effects in 3D vectorial-induced current reconstructions.
AB  - In tomography algorithms, the complex amplitude scattering matrix corresponds to
      the input parameter. When considering 3D targets, the scattering matrix now
      contains vectorial information. Thus, this scattering matrix might be calculated
      with various polarization projections. Moreover, when dealing with experimental
      data, we are almost every time faced with truncated data. We focus here on the
      impact of selecting parts of the amplitude scattering matrix elements versus
      others and in particular on the influence of the polarization choices on the
      imaging results. In order to better apprehend the physical content associated to
      each polarization term, the study is conducted with a simple vectorial-induced
      current reconstruction algorithm allowing reconstruction of qualitative maps of
      the scene. This algorithm is applied on scaled models of aggregates combined with
      experimental scattered fields acquired in the microwave frequency range. 

PMID- 24322852
TI  - Complex reflection coefficients of p- and s-polarized light at the pseudo
      Brewster angle of a dielectric-conductor interface.
AB  - The complex Fresnel reflection coefficients r(p) and r(s) of p- and s-polarized
      light and their ratio rho=r(p)/r(s) at the pseudo-Brewster angle (PBA) phi(pB) of
      a dielectric-conductor interface are evaluated for all possible values of the
      complex relative dielectric function epsilon=|epsilon|exp(-jtheta)=epsilon(r)
      jepsilon(i), epsilon(i)>0 that share the same phi(pB). Complex-plane trajectories
      of r(p), r(s), and rho at the PBA are presented at discrete values of phi(pB)
      from 5 degrees  to 85 degrees  in equal steps of 5 degrees  as theta is increased
      from 0 degrees  to 180 degrees . It is shown that for phi(pB)>70 degrees  (high
      reflectance metals in the IR) r(p) at the PBA is essentially pure negative
      imaginary and the reflection phase shift delta(p)=arg(r(p))~-90 degrees . In the
      domain of fractional optical constants (vacuum UV or light incidence from a high
      refractive-index immersion medium) 0<phi(pB)<45 degrees  and r(p) is pure real
      negative (delta(p)=pi) when theta=tan(-1)(?(cos(2phi(pB)))), and the
      corresponding locus of epsilon in the complex plane is obtained. In the limit of
      epsilon(i)=0, epsilon(r)<0 (interface between a dielectric and plasmonic medium)
      the total reflection phase shifts delta(p), delta(s), Delta=delta(p)
      delta(s)=arg(rho) are also determined as functions of phi(pB).

PMID- 24322853
TI  - Phase diversity for three-dimensional imaging.
AB  - Phase diversity (PD) is a powerful technique for estimating wavefront aberrations
      from two-dimensional images of extended scenes. PD can work with extended
      incoherent images and, in an adaptive optics system, does not need extra hardware
      in addition to the deformable mirror. For these reasons, PD should be well suited
      to aberration measurement in microscopy applications. But, in biological
      widefield microscopy, the objects being imaged are frequently three-dimensional,
      and the images contain out-of-focus light. In this paper, we introduce multiplane
      PD and show that PD can be extended to widefield imaging of three-dimensional
      objects. This should be particularly useful in the field of biological
      fluorescence microscopy where the objects are very light sensitive and the
      aberrations cannot easily be determined. 

PMID- 24322854
TI  - Phase wavefront aberration modeling using Zernike and pseudo-Zernike polynomials.
AB  - Orthogonal polynomials can be used for representing complex surfaces on a
      specific domain. In optics, Zernike polynomials have widespread applications in
      testing optical instruments, measuring wavefront distributions, and aberration
      theory. This orthogonal set on the unit circle has an appropriate matching with
      the shape of optical system components, such as entrance and exit pupils. The
      existence of noise in the process of representation estimation of optical
      surfaces causes a reduction of precision in the process of estimation. Different
      strategies are developed to manage unwanted noise effects and to preserve the
      quality of the estimation. This article studies the modeling of phase wavefront
      aberrations in third-order optics by using a combination of Zernike and pseudo
      Zernike polynomials and shows how this combination may increase the robustness of
      the estimation process of phase wavefront aberration distribution. 

PMID- 24322855
TI  - Deconvolution-based deblurring of reconstructed images in
      photoacoustic/thermoacoustic tomography.
AB  - Photoacoustic/thermoacoustic tomography is an emerging hybrid imaging modality
      combining optical/microwave imaging with ultrasound imaging. Here, a k-wave
      MATLAB toolbox was used to simulate various configurations of excitation pulse
      shape, width, transducer types, and target object sizes to see their effect on
      the photoacoustic/thermoacoustic signals. A numerical blood vessel phantom was
      also used to demonstrate the effect of various excitation pulse waveforms and
      pulse widths on the reconstructed images. Reconstructed images were blurred due
      to the broadening of the pressure waves by the excitation pulse width as well as
      by the limited transducer bandwidth. The blurring increases with increase in
      pulse width. A deconvolution approach is presented here with Tikhonov
      regularization to correct the photoacoustic/thermoacoustic signals, which
      resulted in improved reconstructed images by reducing the blurring effect. It is
      observed that the reconstructed images remain unaffected by change in pulse
      widths or pulse shapes, as well as by the limited bandwidth of the ultrasound
      detectors after the use of the deconvolution technique. 

PMID- 24322856
TI  - Iterative linear focal-plane wavefront correction.
AB  - We propose an efficient approximation to the nonlinear phase diversity (PD)
      method for wavefront reconstruction and correction from intensity measurements
      with potential of being used in real-time applications. The new iterative linear
      phase diversity (ILPD) method assumes that the residual phase aberration is small
      and makes use of a first-order Taylor expansion of the point spread function
      (PSF), which allows for arbitrary (large) diversities in order to optimize the
      phase retrieval. For static disturbances, at each step, the residual phase
      aberration is estimated based on one defocused image by solving a linear least
      squares problem, and compensated for with a deformable mirror. Due to the fact
      that the linear approximation does not have to be updated with each correction
      step, the computational complexity of the method is reduced to that of a matrix
      vector multiplication. The convergence of the ILPD correction steps has been
      investigated and numerically verified. The comparative study that we make
      demonstrates the improved performance in computational time with no decrease in
      accuracy with respect to existing methods that also linearize the PSF. 

PMID- 24322857
TI  - Discretization of continuous convolution operators for accurate modeling of wave
      propagation in digital holography.
AB  - Discretization of continuous (analog) convolution operators by direct sampling of
      the convolution kernel and use of fast Fourier transforms is highly efficient.
      However, it assumes the input and output signals are band-limited, a condition
      rarely met in practice, where signals have finite support or abrupt edges and
      sampling is nonideal. Here, we propose to approximate signals in analog, shift
      invariant function spaces, which do not need to be band-limited, resulting in
      discrete coefficients for which we derive discrete convolution kernels that
      accurately model the analog convolution operator while taking into account
      nonideal sampling devices (such as finite fill-factor cameras). This approach
      retains the efficiency of direct sampling but not its limiting assumption. We
      propose fast forward and inverse algorithms that handle finite-length, periodic,
      and mirror-symmetric signals with rational sampling rates. We provide explicit
      convolution kernels for computing coherent wave propagation in the context of
      digital holography. When compared to band-limited methods in simulations, our
      method leads to fewer reconstruction artifacts when signals have sharp edges or
      when using nonideal sampling devices. 

PMID- 24322858
TI  - Evaporating droplet hologram simulation for digital in-line holography setup with
      divergent beam.
AB  - Generalized Lorenz-Mie theory (GLMT) for a multilayered sphere is used to
      simulate holograms produced by evaporating spherical droplets with refractive
      index gradient in the surrounding air/vapor mixture. Simulated holograms provide
      a physical interpretation of experimental holograms produced by evaporating
      Diethyl Ether droplets with diameter in the order of 50 MUm and recorded in a
      digital in-line holography configuration with a divergent beam. Refractive index
      gradients in the surrounding medium lead to a modification of the center part of
      the droplet holograms, where the first fringe is unusually bright. GLMT
      simulations reproduce this modification well, assuming an exponential decay of
      the refractive index from the droplet surface to infinity. The diverging beam
      effect is also considered. In both evaporating and nonevaporating cases, an
      equivalence is found between Gaussian beam and plane wave illuminations, simply
      based on a magnification ratio to be applied to the droplets' parameters.

PMID- 24322859
TI  - Engineering the smallest 3D symmetrical bright and dark focal spots.
AB  - A simple roadmap is established for the construction of the smallest three
      dimensional (3D) isotropic focal spots. It is achieved in a 4Pi configuration by
      imposing a restriction/condition of equal transverse and longitudinal spot sizes
      to determine the position of an annular aperture and then optimize its size. The
      calculations were performed for cylindrically symmetric radial, azimuthal, and
      circular polarizations for the cases of in-phase and out-of-phase counter
      propagating beams as well as when a vortex was added to the beams. A diffraction
      limited bright 3D isotropic spot containing solely longitudinal or transverse
      electric field components is obtained, while the 3D dark spot can be formed from
      one of two complementary combinations, each containing both transverse and
      longitudinal field components. 

PMID- 24322860
TI  - Semi-analytic impedance modeling of three-dimensional photonic and metamaterial
      structures.
AB  - We define the concept of an impedance matrix for three-dimensional (3D) photonic
      and metamaterial structures relative to a reference medium and show that it
      satisfies a matrix generalization of the basic algebraic properties of the wave
      impedance between homogeneous media. This definition of the impedance matrix is
      motivated by the structure of the Fresnel reflection and transmission matrices at
      the interface between the media. In the derivation of the Fresnel scattering
      matrices, the field in each medium is expressed by a Bloch mode expansion, with
      field matching at the interface being undertaken in a least-squares manner by
      exploiting a biorthogonality relation between primal and adjoint Bloch modes. A
      semi-analytic technique, based on the impedance matrix, is developed for modeling
      the scattering of light by 3D periodic photonic and metamaterial structures. The
      advantages (in design and intuition) of the formalism are demonstrated through
      two applications. 

PMID- 24322861
TI  - A phase mixing model for the frequency-doubling illusion.
AB  - We introduce a temporal phase mixing model for a description of the frequency
      doubling illusion (FDI). The model is generic in the sense that it can be set to
      refer to retinal ganglion cells, lateral geniculate cells, as well as simple
      cells in the primary visual cortex (V1). Model parameters, however, strongly
      suggest that the FDI originates in the cortex. The model shows how noise in the
      response phases of cells in V1, or in further processing of these phases, easily
      produces observed behavior of FDI onset as a function of spatiotemporal
      frequencies. It also shows how this noise can accommodate physiologically
      plausible spatial delays in comparing neural signals over a distance. The model
      offers an explanation for the disappearance of the FDI at sufficiently high
      spatial frequencies via increasingly correlated coding of neighboring grating
      stripes. Further, when the FDI is equated to vanishing perceptual discrimination
      between asynchronous contrast-reversal gratings, the model proposes the
      possibility that the FDI shows a resonance behavior at sufficiently high spatial
      frequencies, by which it is alternately perceived and not perceived in sequential
      temporal frequency bands. 

PMID- 24322862
TI  - Visual adaptation--a reinterpretation: discussion.
AB  - This discussion paper seeks to reshape the contemporary understanding of visual
      adaptation. Received wisdom says that input luminance is scaled down in the
      retina. There is, first, a near-logarithmic compression described by the Naka
      Rushton equation and, second, a control of gain (better attenuation) by feedback
      from the output of each ganglion cell that is equivalent to modifying the half
      saturation constant in the Naka-Rushton equation. The reinterpretation proposed
      here asserts the following instead: (a) the scaling down in the retina is
      accomplished by receptive fields of different areas, which function over
      different ranges of luminance, ranges inversely proportional to the area of the
      receptive field. (b) The visual pathway is differentially coupled to the physical
      stimulus, so that the maintained discharge increases only as the square root of
      the luminance. (c) The Naka-Rushton equation describes merely the saturation of
      neural response as input increases; when a neuron is overloaded, output tends to
      regularity and onward transmission is blocked by a subsequent stage of
      differential coupling. Three existing studies of the relation between input to
      and output from retinal ganglion cells are reinterpreted in the light of this
      alternative view of visual adaptation.

PMID- 24322863
TI  - Hysteretic characteristics of 1/lambda4 scattering of light during adsorption and
      desorption of water in porous Vycor glass with nanopores.
AB  - Porous Vycor glass with nanopores is transparent in the visible region and is
      often used in colorimetric chemical sensing when impregnated with selectively
      reacting reagents. However, it has some disadvantages in sensing, since changes
      in the humidity of ambient air strongly affect its transmission. In this work, by
      combining a humidity-controlled thermostatic chamber and an ultraviolet-visible
      and near-infrared spectrophotometer through fiber optics, we analyzed the effect
      of increasing and decreasing humidity in the ambient air on the transparency
      change of the nanoporous glass. The transparency response in the visible region
      to changes in humidity is analyzed to correlate the turbidity response of the
      glass with the amount of water in it. The turbidity is found to be dependent on
      the inverse fourth power of the wavelength (1/lambda4), which implies that
      Rayleigh-type scattering takes place for both adsorption and desorption of water.
      We show that measures of the extent of the optical inhomogeneity that causes the
      scattering, such as the effective radius of scatterers and their number density,
      exhibit a pronounced hysteretic characteristic for the imbibition and drainage of
      water, while the absorption inherent to imbibed water also shows another type of
      hysteresis that is quite similar to the sorption isotherms of water. On the basis
      of the above observations, we show that the transitory white turbidity of
      nanoporous glasses during changes in humidity can be consistently interpreted and
      quantitatively analyzed by a simple Rayleigh scattering mechanism.

PMID- 24322864
TI  - Asymptotic solutions of eigenmodes in slab waveguides terminated by perfectly
      matched layers.
AB  - For numerical modeling of optical wave-guiding structures, perfectly matched
      layers (PMLs) are widely used to terminate the transverse variables of the
      waveguide. The PML modes are the eigenmodes of a waveguide terminated by PMLs,
      and they have found important applications in the mode matching method, the
      coupled mode theory, and so on. In this paper, we consider PML modes for two
      dimensional slab waveguides. It is shown that the PML modes consist of perturbed
      propagating modes, perturbed leaky modes, and two infinite sequences of Berenger
      modes. High-order asymptotic solutions for the Berenger modes are derived using a
      systematic approach. 

PMID- 24322865
TI  - Differential commuting operator and closed-form eigenfunctions for linear
      canonical transforms.
AB  - The linear canonical transform (LCT) with a, b, c, d parameter plays an important
      role in quantum mechanics, optics, and signal processing. The eigenfunctions of
      the LCT are also important because they describe the self-imaging phenomenon in
      optical systems. However, the existing solutions for the eigenfunctions of the
      LCT are divided into many cases and they lack a systematic way to solve these
      eigenfunctions. In this paper, we find a linear, second-order, self-adjoint
      differential commuting operator that commutes with the LCT operator. Hence, the
      commuting operator and the LCT share the same eigenfunctions with different
      eigenvalues. The commuting operator is very general and simple when it is
      compared to the existing multiple-parameter differential equations. Then, the
      eigenfunctions can be derived systematically. The eigenvalues of the commuting
      operator have closed-form relationships with the eigenvalues of the LCT. We also
      simplify the eigenfunctions for |a+d|>2 and a+d=+/-2, b?0 into the more compact
      closed form instead of the integral form. For |a+d|>2, the eigenfunctions are
      related to the parabolic cylinder functions. 

PMID- 24322866
TI  - Explicit error bounds for the alpha-quasi-periodic Helmholtz problem.
AB  - This paper considers a finite element approach to modeling electromagnetic waves
      in a periodic diffraction grating. In particular, an a priori error estimate
      associated with the alpha-quasi-periodic transformation is derived. This involves
      the solution of the associated Helmholtz problem being written as a product of
      e(ialphax) and an unknown function called the alpha-quasi-periodic solution. To
      begin with, the well-posedness of the continuous problem is examined using a
      variational formulation. The problem is then discretized, and a rigorous a priori
      error estimate, which guarantees the uniqueness of this approximate solution, is
      derived. In previous studies, the continuity of the Dirichlet-to-Neumann map has
      simply been assumed and the dependency of the regularity constant on the system
      parameters, such as the wavenumber, has not been shown. To address this
      deficiency, in this paper an explicit dependence on the wavenumber and the degree
      of the polynomial basis in the a priori error estimate is obtained. Since the
      finite element method is well known for dealing with any geometries, comparison
      of numerical results obtained using the alpha-quasi-periodic transformation with
      a lattice sum technique is then presented.

PMID- 24322867
TI  - Optically amplified detection for biomedical sensing and imaging.
AB  - Optical sensing and imaging methods for biomedical applications, such as
      spectroscopy and laser-scanning fluorescence microscopy, are incapable of
      performing sensitive detection at high scan rates due to the fundamental trade
      off between sensitivity and speed. This is because fewer photons are detected
      during short integration times and hence the signal falls below the detector
      noise. Optical postamplification can, however, overcome this challenge by
      amplifying the collected optical signal after collection and before
      photodetection. Here we present a theoretical analysis of the sensitivity of high
      speed biomedical sensing and imaging systems enhanced by optical postamplifiers.
      As a case study, we focus on Raman amplifiers because they produce gain at any
      wavelength within the gain medium's transparency window and are hence suitable
      for biomedical applications. Our analytical model shows that when limited by
      detector noise, such optically postamplified systems can achieve a sensitivity
      improvement of up to 20 dB in the visible to near-infrared spectral range without
      sacrificing speed. This analysis is expected to be valuable for design of fast
      real-time biomedical sensing and imaging systems.

PMID- 24322868
TI  - High-resolution tomographic diffractive microscopy in reflection configuration.
AB  - Tomographic diffractive microscopy (TDM) is a label-free imaging technique that
      reconstructs the 3D refractive index map of the probed object with an improved
      resolution compared to confocal microscopy. In this work, we consider a TDM
      implementation in which the sample is deposited on a reflective substrate. We
      show that this configuration requires calibration and inversion procedures that
      account for the presence of the substrate for getting highly resolved
      quantitative reconstructions. 

PMID- 24322869
TI  - Computation of the diffracted field of a toothed occulter by the semi-infinite
      rectangle method.
AB  - To observe the solar corona, stray light in the coronagraph, arising primarily
      from an external occulter and diaphragm illuminated directly by the Sun, should
      be strongly suppressed. A toothed occulter and diaphragm can be used to suppress
      stray light because they diffract much less light in the central area than a
      circular disk. This study develops a method of computing the light diffracted by
      a toothed occulter and diaphragm, obtaining the optimum shape using this method.
      To prove the method's feasibility, the diffracted fields of circular and
      rectangular disks are computed and compared with those calculated by a
      conventional method. 

PMID- 24322870
TI  - Balanced diffraction aberrations, independent of the observation point:
      application to a tilted dielectric plate.
AB  - Balancing of Zernike aberrations breaks down if the defocus term is large enough
      that the condition (z/lambda)?2/[pi(NA)4] is not satisfied. A modified Zernike
      aberration expansion, based on the Zernike aberrations, is developed that
      accurately includes axial displacement as a low-order term, even for large
      displacements. This expansion can be used to analyze aberrations for on-axis
      illumination of a high numerical aperture system. But more importantly, for
      systems of moderate numerical aperture it allows balanced aberration coefficients
      to be determined independent of the assumption of a particular reference point.
      The approach is applied to the case of a tilted dielectric plate. An exact
      expression is given for the wave front aberration, valid for both large angles of
      tilt and high beam convergence angles, that is independent of observation
      distance. Analytical expressions for the third- and fifth-order aberration
      coefficients are derived. Expressions are given for expansion of multiple-angle
      power series terms into Zernike polynomials.

PMID- 24322871
TI  - Validation of the AVITA BPM63S upper arm blood pressure monitor for home blood
      pressure monitoring according to the European Society of Hypertension
      International Protocol revision 2010.
AB  - OBJECTIVE: The present study aimed to evaluate the accuracy of the AVITA BPM63S
      upper arm blood pressure monitor for home blood pressure monitoring according to
      the International Protocol of the European Society of Hypertension revision 2010.
      METHODS: Systolic and diastolic blood pressures were sequentially measured in 33
      adult Chinese (14 women, mean age of 47 years) using a mercury sphygmomanometer
      (two observers) and the AVITA BPM63S device (one supervisor). Ninety-nine pairs
      of comparisons were obtained from 33 participants for judgments in two parts with
      three grading phases. RESULTS: All the blood pressure requirements were
      fulfilled. The AVITA BPM63S device achieved the targets in part 1 of the
      validation study. The number of absolute differences between device and observers
      within 5, 10, and 15 mmHg was 68/99, 89/99, and 96/99, respectively, for systolic
      blood pressure, and 75/99, 95/99, and 97/99, respectively, for diastolic blood
      pressure. The device also achieved the criteria in part 2 of the validation
      study. Twenty-four and 25 participants for systolic and diastolic blood pressure,
      respectively, had at least two of the three device-observers differences within 5
      mmHg (required >=24). One and two participants for systolic and diastolic blood
      pressure, respectively, had all three device-observers differences greater than 5
      mmHg. CONCLUSION: The AVITA BPM63S automated oscillometric upper arm blood
      pressure monitor has passed the requirements of the International Protocol
      revision 2010, and hence can be recommended for blood pressure measurement at
      home in adults.

PMID- 24322872
TI  - Activity of mesenchymal stem cells in therapies for chronic skin wound healing.
AB  - Chronic or non-healing skin wounds present an ongoing challenge in advanced wound
      care, particularly as the number of patients increases while technology aimed at
      stimulating wound healing in these cases remains inefficient. Mesenchymal stem
      cells (MSCs) have proved to be an attractive cell type for various cell therapies
      due to their ability to differentiate into various cell lineages, multiple donor
      tissue types, and relative resilience in ex-vivo expansion, as well as
      immunomodulatory effects during transplants. More recently, these cells have been
      targeted for use in strategies to improve chronic wound healing in patients with
      diabetic ulcers or other stasis wounds. Here, we outline several mechanisms by
      which MSCs can improve healing outcomes in these cases, including reducing tissue
      inflammation, inducing angiogenesis in the wound bed, and reducing scarring
      following the repair process. Approaches to extend MSC life span in implant sites
      are also examined. 

PMID- 24322875
TI  - Western scrub-jays allocate longer observation time to more valuable information.
AB  - When humans mentally reconstruct past events and imagine future scenarios, their
      subjective experience of mentally time travelling is accompanied by the awareness
      of doing so. Despite recent popularity of studying episodic memory in animals,
      such phenomenological consciousness has been extremely difficult to demonstrate
      without agreed behavioural markers of consciousness in non-linguistic subjects.
      We presented western scrub-jays (Aphelocoma californica) with a task requiring
      them to allocate observing time between two peepholes to see food being hidden in
      either of two compartments, one where observing the hiding location was necessary
      to later relocate the food, and another where food could easily be found without
      watching. Jays first separately experienced these consequences of possessing
      information in each compartment and subsequently, once given a choice, made more
      looks and spent more time looking into the compartment where information was
      necessary than into the compartment where it was unnecessary. Thus, the jays can
      collect information to solve a future problem. Moreover, they can differentiate
      sources of information according to their potential value and modify behaviour to
      efficiently collect important, usable information. This is the first evidence of
      metacognition in a species that passes the behavioural criteria for both
      retrospective and prospective mental time travel. 

PMID- 24322874
TI  - Influence of personality, age, sex, and estrous state on chimpanzee problem
      solving success.
AB  - Despite the importance of individual problem solvers for group- and individual
      level fitness, the correlates of individual problem-solving success are still an
      open topic of investigation. In addition to demographic factors, such as age or
      sex, certain personality dimensions have also been revealed as reliable
      correlates of problem-solving by animals. Such correlates, however, have been
      little-studied in chimpanzees. To empirically test the influence of age, sex,
      estrous state, and different personality factors on chimpanzee problem-solving,
      we individually tested 36 captive chimpanzees with two novel foraging puzzles. We
      included both female (N=24) and male (N=12) adult chimpanzees (aged 14-47 years)
      in our sample. We also controlled for the females' estrous state-a potential
      influence on cognitive reasoning-by testing cycling females both when their
      sexual swelling was maximally tumescent (associated with the luteinizing hormone
      surge of a female's estrous cycle) and again when it was detumescent. Although we
      found no correlation between the chimpanzees' success with either puzzle and
      their age or sex, the chimpanzees' personality ratings did correlate with
      responses to the novel foraging puzzles. Specifically, male chimpanzees that were
      rated highly on the factors Methodical, Openness (to experience), and Dominance
      spent longer interacting with the puzzles. There was also a positive relationship
      between the latency of females to begin interacting with the two tasks and their
      rating on the factor Reactivity/Undependability. No other significant
      correlations were found, but we report tentative evidence for increased problem
      solving success by the females when they had detumescent estrous swellings.

PMID- 24322876
TI  - Peristomal epidermolysis bullosa acquisita in a patient with Crohn's disease.

PMID- 24322877
TI  - Target-mediated drug disposition model and its approximations for antibody-drug
      conjugates.
AB  - Antibody-drug conjugate (ADC) is a complex structure composed of an antibody
      linked to several molecules of a biologically active cytotoxic drug. The number
      of ADC compounds in clinical development now exceeds 30, with two of them already
      on the market. However, there is no rigorous mechanistic model that describes
      pharmacokinetic (PK) properties of these compounds. PK modeling of ADCs is even
      more complicated than that of other biologics as the model should describe
      distribution, binding, and elimination of antibodies with different toxin load,
      and also the deconjugation process and PK of the released toxin. This work
      extends the target-mediated drug disposition (TMDD) model to describe ADCs,
      derives the rapid binding (quasi-equilibrium), quasi-steady-state, and Michaelis
      Menten approximations of the TMDD model as applied to ADCs, derives the TMDD
      model and its approximations for ADCs with load-independent properties, and
      discusses further simplifications of the system under various assumptions. The
      developed models are shown to describe data simulated from the available clinical
      population PK models of trastuzumab emtansine (T-DM1), one of the two currently
      approved ADCs. Identifiability of model parameters is also discussed and
      illustrated on the simulated T-DM1 examples. 

PMID- 24322878
TI  - Bacterial skin commensals and their role as host guardians.
AB  - Recent years' investigations of the co-evolution and functional integration of
      the human body and its commensal microbiota have disclosed that the microbiome
      has a major impact on physiological functions including protection against
      infections, reaction patterns in the immune system, and disposition for
      inflammation-mediated diseases. Two ubiquitous members of the skin microbiota,
      the Gram-positive bacteria Staphylococcus epidermidis and Propionibacterium
      acnes, are predominant on human epithelia and in sebaceous follicles,
      respectively. Their successful colonisation is a result of a commensal or even
      mutualistic lifestyle, favouring traits conferring persistency over aggressive
      host-damaging properties. Some bacterial properties suggest an alliance with the
      host to keep transient, potential pathogens at bay, such as the ability of S.
      epidermidis to produce antimicrobials, or the production of short-chain fatty
      acids by P. acnes. These features can function together with host-derived
      components of the innate host defence to establish and maintain the composition
      of a health-associated skin microbiota. However, depending largely on the host
      status, the relationship between the human host and S. epidermidis/P. acnes can
      also have parasitic features. Both microorganisms are frequently isolated from
      opportunistic infections. S. epidermidis is a causative agent of hospital
      acquired infections, mostly associated with the use of medical devices. P. acnes
      is suspected to be of major importance in the pathogenesis of acne and also in a
      number of other opportunistic infections. In this review we will present
      bacterial factors and traits of these two key members of our skin microbiota and
      discuss how they contribute to mutualistic and parasitic properties. The
      elucidation of their roles in health-promoting or disease-causing processes could
      lead to new prophylactic and therapeutic strategies against skin disorders and
      other S. epidermidis/P. acnes-associated diseases, and increase our understanding
      of the delicate interplay of the skin microbiota with the human host. 

PMID- 24322879
TI  - Randomised double-blind placebo-controlled study of the effect of Lactobacillus
      paracasei NCC 2461 on skin reactivity.
AB  - In recent decades, the prevalence of subjects with reactive skin has considerably
      increased in industrialised countries. 50% of women and 30% of men report
      cutaneous discomfort classified under reactive/sensitive skin. Several topical
      approaches have been proposed, in particular through improvement of galenic forms
      or protection of epidermal surface. We propose to act differently, deeply from
      inside the body via an innovative nutritional approach. To this purpose,
      Lactobacillus paracasei NCC 2461 (ST11) was selected because of its specific
      beneficial skin properties discovered in in vitro studies, i.e. diminution of
      neurogenic inflammation and promotion of the recovery of skin barrier function.
      We designed a randomised double-blind placebo-controlled clinical study with a
      two-month supplementation in two female treatment groups (n=32 per group). A
      capsaicin test was performed to monitor the time course of skin sensitivity.
      Moreover, transepidermal water loss was assessed to analyse the rate of skin
      barrier function recovery; dryness of the leg and roughness of the cheeks was
      investigated by a dermatologist as well as by self-assessment. The results of the
      present clinical trial show that oral supplementation with the probiotic
      decreases skin sensitivity and increases the rate of barrier function recovery.
      Thus, the data provide evidence that daily intake of ST11 could improve reactive
      skin condition. 

PMID- 24322880
TI  - Immune modulation property of Lactobacillus paracasei NCC2461 (ST11) strain and
      impact on skin defences.
AB  - The gut intestinal tract harbours a complex microbiota. Disturbances in the
      microbiota composition have been associated with several immune dysfunctions such
      as inflammatory diseases. Specific strains of probiotics have shown to
      beneficially influence the composition and/or metabolic activity of the
      endogenous microbiota. Taking advantage of the plasticity of the immune system,
      the probiotic strain NCC2461 (i.e. ST11 or CNCM I-2116) supports and/or restores
      homeostasis in reaction to different physiopathological conditions. The potential
      of NCC2461 to modulate both mucosal and systemic immune functions led us to test
      its impact on skin physiology. Even though clear mechanisms explaining gut-skin
      interaction are still lacking, a set of experimental and clinical data reviewed
      herein have shown that NCC2461 exerts its effects beyond the gut and confers
      benefits at the skin level. It contributes to the reinforcement of skin barrier
      function, decreases skin sensitivity and modulates the skin immune system leading
      to the preservation of skin homeostasis. 

PMID- 24322881
TI  - Transient inflammatory-like state and microbial dysbiosis are pivotal in
      establishment of mucosal homeostasis during colonisation of germ-free mice.
AB  - The gut microbiota is increasingly recognised as a key-player in defining the
      health status of the gastrointestinal tract. Recently, we demonstrated that
      colonisation of healthy germfree mice with a conventional microbiota
      (conventionalisation) elicits temporal and region specific host-microbe
      communication responses that lead to the establishment of a microbiota
      accommodating homeostatic state within 30 days. Here, the microbiota composition
      profiles, mucosal transcriptomes and plasma-analytes in germ-free and
      conventionalised C57/BL 6 J mice were assessed to decipher the features of the
      distinctive and pivotal events occurring four days after initiation of the
      conventionalisation process. The dominance of the microbial genera Helicobacter,
      Sphingomonas and Mucispirillum in the gut microbiota coincided with the transient
      mounting of proinflammatory responses in the mucosa and the transiently elevated
      levels of specific (inflammatory) cytokines and amines in plasma. The
      overrepresented microbes have previously been associated with the potential to
      cause disease under certain conditions, illustrating that conventionalisation
      proceeds through a transient state that resembles situations associated with
      dysbiosis. However, no overt mucosal inflammation was observed, suggesting a
      pivotal role of the overrepresented bacterial groups in priming and maturation of
      the immune system during the process of conventionalisation. These findings imply
      that the transiently elevated relative overgrowth of particular microbial genera
      functions as pivotal adjuvants to elicit the corresponding proinflammatory
      cascades, which precede the full maturation of the different arms of the immune
      system following these events and is required to achieve a microbiota
      accommodating homeostasis in healthy animals. 

PMID- 24322882
TI  - Enzymatic formation of a novel cell-adhesive hydrogel based on small peptides
      with a laterally grafted l-3,4-dihydroxyphenylalanine group.
AB  - We rationally designed a bioadhesive supramolecular hydrogel by introducing L-3,4
      dihydroxylphenylalanine (DOPA) groups while properly integrating the enzymatic
      reactions and self-assembly processes. The effective presence of the catechol
      groups successfully promoted the adhesion and proliferation of human fibroblast
      cells.

PMID- 24322883
TI  - Steroid-resistant relapsing IgG4-related pachymeningitis treated with
      methotrexate.
AB  - IMPORTANCE: IgG4-related disease, which is newly recognized, is characterized by
      lymphoplasmacytic infiltration with increased IgG4-secreting plasma cells.
      Although a favorable response to steroids has previously been reported, the
      durations of follow-up to confirm the long-term benefits and clinical courses
      were limited. We describe long-term favorable response of oral methotrexate in a
      patient with IgG4-related pachymeningitis who was resistant to steroid therapy.
      OBSERVATIONS: A patient in his mid-60s with pathologically proven IgG4-related
      pachymeningitis who was resistant to steroid therapy and experienced an
      exacerbation of symptoms 4 times is described. Low-dose oral methotrexate induced
      significant clinical and radiological improvement, with sustained remission of
      the disease over 2 years without complications. CONCLUSIONS AND RELEVANCE: The
      long-term favorable response to oral methotrexate in the current patient suggests
      that methotrexate is a useful alternative treatment option in patients with IgG4
      related pachymeningitis who are resistant to steroid therapy or who experience
      adverse effects from steroids.

PMID- 24322884
TI  - A rhodamine/BODIPY-based fluorescent probe for the differential detection of
      Hg(II) and Au(III).
AB  - We described the design and synthesis of a molecular sensor based on a
      rhodamine/BODIPY platform that displayed differential fluorescence responses
      towards Hg(2+) and Au(3+) and demonstrated its utility in intracellular ion
      imaging. 

PMID- 24322886
TI  - Nitric oxide is involved in the down-regulation of SOST expression induced by
      mechanical loading.
AB  - Mechanical stimulation reduces sclerostin expression in rodents. However, few
      data are available about the effect of physical stimuli in human systems.
      Recently we observed that the demethylating agent AzadC induces SOST expression
      in bone cells. This allowed us in this study to explore the effect of mechanical
      loading on SOST expression by subjecting AzadC-treated human bone cells to
      pulsating fluid flow (PFF). PFF significantly decreased the AzadC-induced
      expression of SOST. This effect persisted for at least 24 h, and in fact SOST
      expression was lower at 24 h after PFF treatment than at 1 h after PFF treatment
      (PFF/static ratio 0.47 +/- 0.04 vs. 0.63 +/- 0.03 respectively, p = 0.03). The
      PFF-induced decrease in SOST expression was not due to a change in the
      methylation profile of the SOST promoter. However, PFF stimulated nitric oxide
      (NO) synthesis, which appeared essential for the PFF effect on SOST expression.
      In fact, the NO synthase inhibitor 1400 W prevented the effect of PFF on SOST
      expression. Moreover, the NO-donor SNAP decreased SOST mRNA in bone organ
      cultures. The conditioned medium (CM) of cells subjected to PFF induced a 38 +/-
      4 % decrease in SOST expression (p = 0.03) in static cultures and diminished the
      transcriptional activity of reporter vectors with the cloned SOST promoter
      (Static-CM: 1.47 +/- 0.10 vs. PFF-CM: 0.78 +/- 0.09, p = 0.02). This is
      consistent with a PFF-induced secretion of factors that modulate SOST. Our
      results suggest that NO and other soluble factors are involved in the inhibition
      of SOST expression by PFF.

PMID- 24322885
TI  - Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit
      profiles between control and Charcot patient osteoclasts.
AB  - We hypothesized that newly formed osteoclasts from patients with acute Charcot
      osteoarthropathy can resorb surfaces of bone more extensively compared with
      controls. Peripheral blood monocytes, isolated from eight Charcot patients and
      nine controls, were cultured in vitro on 24-well plates and bovine bone discs in
      duplicate with macrophage colony-stimulating factor (M-CSF) and receptor
      activator of nuclear factor kappabeta ligand (RANKL). Osteoclast formation was
      assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17.
      Resorption was measured at day 21 after toluidine blue staining by two methods:
      (1) area of resorption at the surface by image analysis (%) and (2) area of
      resorption under the surface (MUm(2)) measured by a Dektak 150 Surface Profiler.
      Ten 1,000 MUm-long scans were performed per disc. Pits were classified as
      unidented, bidented, and multidented according to their shape. Although the
      number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was
      similar in M-CSF + RANKL-treated cultures between controls and Charcot patients,
      the latter exhibited increased resorbing activity. The area of resorption on the
      surface by image analysis was significantly greater in Charcot patients compared
      with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th
      percentile], p < 0.01), as was the area of resorption under the surface (2.7 x
      10(3) MUm(2) [1.6 x 10(3)- 3.9 x 10(3)] vs. 8.3 x 10(3) MUm (2) [5.6 x 10(3)-
      10.6 x 10(3), [corrected] p < 0.01) after profilometry. In Charcot patients pits
      were deeper and wider and more frequently presented as multidented pits. This
      application of the Dektak 150 Surface Profiler revealed novel differences in
      resorption pit profile from osteoclasts derived from Charcot patients compared
      with controls. Resorption in Charcot patients was mediated by highly aggressive
      newly formed osteoclasts from monocytes eroding large and deep areas of bone.

PMID- 24322887
TI  - Dual antiplatelet therapy after drug-eluting stents: defining the proper
      duration.
AB  - As compared with bare-metal stents, drug-eluting stents (DESs) reduce restenosis
      in every clinical situation and every type of lesion studied. Therefore, DESs
      have been in widespread use for more than a decade and are used in the majority
      of patients receiving intracoronary stents. However, several studies have
      suggested that early discontinuation of dual antiplatelet therapy (DAPT; the
      combination of aspirin and an inhibitor of platelet P2Y12) is associated with a
      greater risk for 'late' stent thrombosis in patients with DESs. Because of the
      relative risk and benefit associated with DESs and the use of DAPT, perhaps the
      most common question for the treating physicians and patients are with regard to
      the appropriate duration of DAPT for patients treated with DES implantation.
      Several observational studies have shown inconsistent findings with respect to
      the optimal duration of DAPT after DES implantation. Subsequent randomized
      clinical trials have indicated that courses of clopidogrel exceeding 12 months do
      not contribute favorably to patient outcomes and may in fact be detrimental. No
      sound evidence is available to support prolongation of DAPT beyond 12 months. On
      the basis of recent clinical studies, a shorter course of DAPT than recommended
      by the guidelines (at least 12 months in the ACCF/AHA/SCAI guideline and 6-12
      months in the European Society of Cardiology guidelines) may be considered,
      especially with second-generation or newer-generation DESs being associated with
      a significant reduction in stent thrombosis compared with first-generation DES.
      However, as these trials also had insufficient statistical power to allow for a
      firm decision with regard to the optimal DAPT duration after DES implantation,
      the results of larger ongoing clinical trials are necessary to resolve this issue
      before changing the practice. This article systematically reviews the cumulative
      evidence from key clinical studies and tries to help guide the physician in
      making informed decisions on the optimal duration of DAPT for patients who are
      undergoing DES implantation. 

PMID- 24322888
TI  - Dynamic pulmonary computed tomography angiography: a new standard for evaluation
      of combined airway and vascular abnormalities in infants.
AB  - Airway abnormalities are frequently associated with congenital heart disease in
      infants and children. Respiratory distress in these children frequently requires
      prolonged respiratory support. Wide-detector dynamic pulmonary computed
      tomography angiography (DP-CTA) is a non-invasive technique that completely
      evaluates vascular and airway abnormalities during a single breathe. Our purpose
      was to evaluate the efficacy of DP-CTA to provide unique actionable information
      for patient care in newborns and infants with congenital heart disease and
      persistent respiratory distress. 23 infants with congenital heart disease and
      persistent respiratory distress underwent DP-CTA. All were intubated at the time
      of the examinations. The most common cardiac anomalies were tetralogy of Fallot
      (6) and hypoplastic left heart syndrome variants (5). The most common cardiac
      surgeries prior to DP-CTA were Norwood (4) and hybrid (3) procedures. The
      protocol for DP-CTA for intubated infants is four gantry rotations in 1.4 s after
      intravenous contrast injection. 3D and multiplanar reconstruction with cine loops
      were created for combined cardiopulmonary imaging. Tracheobronchomalacia was
      present in 17 children. Lobar bronchomalacia was identified in six children.
      Branch pulmonary artery stenosis was the most common vascular finding (10
      children). Medical management was changed or a surgical procedure performed based
      on the information resulting from DP-CTA in 16 of the 23 patients (70 %). DP-CTA
      is non-invasive, fast and provides unique information for the management of
      infants with congenital heart disease and persistent respiratory distress. DP-CTA
      is uniquely suited for comprehensive and simultaneous evaluation of airway and
      vascular abnormalities in infants.

PMID- 24322889
TI  - Echocardiographic measurement methods for left ventricular linear dimensions in
      children result in predictable variations in results.
AB  - Precise quantification of left ventricular (LV) cavity dimensions assumes great
      importance in clinical cardiology. Pediatric guidelines recommend the left
      parasternal short axis (PSA) imaging plane for measuring LV cavity dimensions,
      while measuring from the long axis (PLA) plane is the convention in adult
      echocardiography. We sought to compare measurements obtained by two-dimensional
      (2D) and M-mode (MM) techniques in the two imaging planes. Healthy subjects were
      prospectively recruited for research echocardiography. Complete 2D, spectral and
      color flow Doppler examinations were performed in a non-sedated state. All
      subjects had structurally and functionally normal hearts. LV cavity dimensions
      were obtained in PLA and PSA views using 2D and MM yielding four measurement sets
      for each subject: PLA direct 2D; PLA 2D-guided MM, PSA direct 2D, PSA 2D-guided
      MM. A commercially available ultrasound system (Vivid E9, GE) was used and data
      stored digitally for subsequent analysis (EchoPAC BT11, GE). Acquisition and
      measurements were made by a single observer from at least three consecutive
      cardiac cycles, and averaged for each of the four categories. The study cohort
      consisted of 114 subjects (mean age 9 years, range 1-18; mean BSA 1.1 m(2), range
      0.42-2.6). The smallest estimate of LV end-diastolic dimension (LVED) was
      obtained by PLA 2D, with larger estimates by PLA MM, PSA 2D, and PSA MM. Largest
      estimates of LV end-systolic dimension (LVES) are by 2D methods, with smaller
      estimates by both MM techniques. The smallest shortening fraction (SF) was by PLA
      2D; other methods yielded larger SF. Temporal resolution is limited in 2D
      methodology and may account for the smaller LVED, larger LVES and smaller SF
      observed. Long axis methodology may predispose to off-center or non-perpendicular
      data acquisition and the potential for dimensional underestimation, particularly
      in diastole. Consistency in method for assessment of LV dimensions in children is
      an important factor for serial comparisons.

PMID- 24322890
TI  - Sulphoxythiocarbamates modify cysteine residues in HSP90 causing degradation of
      client proteins and inhibition of cancer cell proliferation.
AB  - BACKGROUND: Heat shock protein 90 (HSP90) has a key role in the maintenance of
      the cellular proteostasis. However, HSP90 is also involved in stabilisation of
      oncogenic client proteins and facilitates oncogene addiction and cancer cell
      survival. The development of HSP90 inhibitors for cancer treatment is an area of
      growing interest as such agents can affect multiple pathways that are linked to
      all hallmarks of cancer. This study aimed to test the hypothesis that targeting
      cysteine residues of HSP90 will lead to degradation of client proteins and
      inhibition of cancer cell proliferation. METHODS: Combining chemical synthesis,
      biological evaluation, and structure-activity relationship analysis, we
      identified a new class of HSP90 inhibitors. Click chemistry and protease-mass
      spectrometry established the sites of modification of the chaperone. RESULTS: The
      mildly electrophilic sulphoxythiocarbamate alkyne (STCA) selectively targets
      cysteine residues of HSP90, forming stable thiocarbamate adducts. Without
      interfering with the ATP-binding ability of the chaperone, STCA destabilises the
      client proteins RAF1, HER2, CDK1, CHK1, and mutant p53, and decreases
      proliferation of breast cancer cells. Addition of a phenyl or a tert-butyl group
      in tandem with the benzyl substituent at nitrogen increased the potency. A new
      compound, S-4, was identified as the most robust HSP90 inhibitor within a series
      of 19 derivatives. CONCLUSION: By virtue of their cysteine reactivity,
      sulphoxythiocarbamates target HSP90, causing destabilisation of its client
      oncoproteins and inhibiting cell proliferation.

PMID- 24322892
TI  - Carbon dioxide adsorption on a ZnO(101[combining macron]0) substrate studied by
      infrared reflection absorption spectroscopy.
AB  - The adsorption of carbon dioxide on the mixed-terminated ZnO(101[combining
      macron]0) surface of a bulk single crystal was studied by UHV Infrared Reflection
      Absorption Spectroscopy (IRRAS). In contrast to metals, the classic surface
      selection rule for IRRAS does not apply to bulk oxide crystals, and hence
      vibrational bands can also be observed for s-polarized light. Although this fact
      substantially complicates data interpretation, a careful analysis allows for a
      direct determination of the adsorbate geometry. Here, we demonstrate the huge
      potential of IR-spectroscopy for investigations on oxide single crystal surfaces
      by considering all three components of the incident polarized light separately.
      We find that the tridentate (surface) carbonate is aligned along the [0001]
      direction. A comparison to data reported previously for CO2 adsorbed on the
      surfaces of ZnO nanoparticles provides important insight into the role of defects
      in the surface chemistry of powder particles.

PMID- 24322891
TI  - c-FOS suppresses ovarian cancer progression by changing adhesion.
AB  - BACKGROUND: C-Fos was initially described as oncogene, but was associated with
      favourable prognosis in ovarian cancer (OvCa) patients. The molecular and
      functional aspects underlying this effect are still unknown. METHODS: Using
      stable transfectants of SKOV3 and OVCAR8 cells, proliferation, migration,
      invasion and apoptotic potential of c-FOS-overexpressing clones and controls were
      compared. Adherence to components of the extracellular matrix was analysed in
      static assays, and adhesion to E-selectin, endothelial and mesothelial cells in
      dynamic flow assays. The effect of c-FOS in vivo was studied after
      intraperitoneal injection of SKOV3 clones into SCID mice, and changes in gene
      expression were determined by microarray analysis. RESULTS: Tumour growth after
      injection into SCID mice was strongly delayed by c-FOS overexpression, with
      reduction of lung metastases and circulating tumour cells. In vitro, c-FOS had
      only weak influence on proliferation and migration, but was strongly pro
      apoptotic. Adhesion to components of the extracellular matrix (collagen I, IV)
      and to E-selectin, endothelial and mesothelial cells was significantly reduced in
      c-FOS-overexpressing OvCa cells. This corresponds to deregulation of adhesion
      proteins and glycosylation enzymes in microarray analysis. CONCLUSION: In
      addition to its known pro-apoptotic effect, c-FOS might influence OvCa
      progression by changing the adhesion of OvCa cells to peritoneal surfaces.

PMID- 24322893
TI  - Life history and resource acquisition: Photosynthetic traits in selected
      accessions of three perennial cereal species compared with annual wheat and rye.
AB  - PREMISE OF THE STUDY: Few previous studies have considered how plant age affects
      photosynthetic physiology in herbaceous perennials or how photosynthetic capacity
      in annual cereals compares to perennial relatives. Newly developed perennial
      cereals offer novel systems for addressing these questions. Our study makes a
      novel contribution by considering how life history differences affect
      photosynthetic physiology. METHODS: In two linked field studies, we evaluated
      effects of life history and plant age on photosynthetic rates (A), and related
      biochemical, morphological, and water-relations traits, comparing 1- and 2-yr-old
      cohorts of perennial wheat, intermediate wheatgrass, and perennial rye to close
      annual relatives (wheat and rye). KEY RESULTS: Photosynthetic rates (A) were 10
      50% higher in perennial cereals compared to annuals. In wheatgrass, elevated A
      was associated with higher carboxylation (VC), triose phosphate utilization (TPU)
      and electron transport rates (J), and higher leaf soluble protein and
      chlorophyll. Younger wheatgrass plants maintained higher A, TPU, J, and VC than
      older plants did. Perennial wheat and rye differed from annual relatives in some
      but not all of these parameters. Differences in stomatal limitation were not
      involved, while differences in stomatal conductance (gs) became evident under
      drier conditions. CONCLUSIONS: This study demonstrates that some perennial cereal
      species can maintain higher midseason A than their annual crop relatives. These
      changes are not fully explainable by increased access to soil water and may
      reflect trade-offs between allocation to reproduction and to resource
      acquisition. We also found evidence for age-related changes in photosynthetic
      physiology in a herbaceous perennial plant.

PMID- 24322894
TI  - Intrusive trichome bases in the leaves of silverleaf nightshade (Solanum
      elaeagnifolium; Solanaceae) do not facilitate fluorescent tracer uptake.
AB  - PREMISE OF THE STUDY: Solanum elaeagnifolium (silverleaf nightshade), having
      originated in the Americas, is now a serious summer-growing, perennial weed in
      many countries, including Australia. Most surfaces of the plants have a dense
      covering of trichomes, giving them a silvery-white appearance, hence the common
      name. We aimed to identify structural and functional properties of its leaves,
      especially the trichomes, that may affect the uptake of foliar-applied tracer
      dyes. METHODS: The structure of leaves of Solanum elaeagnifolium was examined by
      light and scanning electron microscopy. The potential for transport of materials
      between trichomes and veins was studied with symplastic (carboxyfluorescein
      diacetate) and apoplastic (lucifer yellow) tracer dyes. KEY RESULTS: Mature
      leaves had a dense covering of complex, stellate trichomes on both surfaces,
      particularly the abaxial. The basal cells of Solanum elaeagnifolium trichomes
      penetrated into the underlying palisade mesophyll layers. The innermost lobes of
      these basal cells sometimes contacted the bundle sheath of the veins, but were
      not observed to directly contact the xylem or phloem. We found that neither
      symplastic nor apoplastic dyes were transferred between the basal cells of the
      trichomes and the vascular tissues. The trichome layer repelled water-based
      tracer dyes, while one of four adjuvants tested facilitated entry of both
      symplastic and apoplastic dyes. CONCLUSIONS: Our results did not support a
      transport function for the trichomes. The trichomes may protect the mesophytic
      leaves from invertebrate herbivory, while also probably decreasing radiation
      absorbed resulting in cooler leaves in this summer-growing species.

PMID- 24322895
TI  - Neural stem cell therapies for enteric nervous system disorders.
AB  - The enteric nervous system is vulnerable to a range of congenital and acquired
      disorders that disrupt the function of its neurons or lead to their loss. The
      resulting enteric neuropathies are some of the most challenging clinical
      conditions to manage. Neural stem cells offer the prospect of a cure given their
      potential ability to replenish missing or dysfunctional neurons. This article
      discusses diseases that might be targets for stem cell therapies and the barriers
      that could limit treatment application. We explore various sources of stem cells
      and the proof of concept for their use. The critical steps that remain to be
      addressed before these therapies can be used in patients are also discussed. Key
      milestones include the harvesting of neural stem cells from the human gut and the
      latest in vivo transplantation studies in animals. The tremendous progress in the
      field has brought experimental studies exploring the potential of stem cell
      therapies for the management of enteric neuropathies to the cusp of clinical
      application.

PMID- 24322896
TI  - Barrett oesophagus in 2013: risk stratification and surveillance in Barrett
      oesophagus.
AB  - Advances are being made in understanding the pathogenesis, treatment outcomes and
      surveillance of Barrett oesophagus. Central obesity and age at onset of gastro
      oesophageal reflux are being recognized as risk factors that have implications
      for screening. The persistent finding of nondysplastic Barrett oesophagus during
      surveillance is associated with low risk of malignant progression, whereas
      dysplastic Barrett oesophagus requires continued surveillance.

PMID- 24322897
TI  - Liver: hepatic stellate cells hold the key to liver fibrosis.

PMID- 24322900
TI  - Coeliac disease in 2013: new insights in dietary-gluten-induced autoimmunity.
AB  - Coeliac disease comprises intolerance against dietary wheat, rye and barley
      gluten and is one of the most common food-related life-long disorders in Western
      countries. In 2013, new knowledge of the clinical diversity of coeliac disease
      and further details about the autoimmune aspects of this disorder have emerged.

PMID- 24322902
TI  - Gut microbiota: Anti-cancer therapies affected by gut microbiota.

PMID- 24322903
TI  - Pancreatic cancer: Sorafenib: no effect on efficacy of chemotherapy in pancreatic
      cancer.

PMID- 24322905
TI  - Molecular imaging of myocardial infarction.
AB  - Myocardial infarction (MI), and subsequent heart failure, remains a major
      healthcare problem in the western and developing world and leads to substantial
      morbidity and mortality. After MI, the ability of the myocardium to recover is
      closely associated with a complex immune response that often leads to adverse
      remodeling of the ventricle, and poor prognosis. Currently used clinical imaging
      modalities allow the assessment of anatomy, perfusion, function, and viability
      but do not provide insights into specific biological processes. In contrast,
      novel non-invasive imaging methods, using targeted imaging agents, allow imaging
      of the molecular processes underlying the post-MI immune cell response, and
      subsequent remodeling. Therefore, this may have significant diagnostic,
      prognostic, and therapeutic value, and may help to improve our understanding of
      post-infarct remodeling, in vivo. Imaging modalities such as magnetic resonance
      imaging, single-photon emission computed tomography, and positron emission
      tomography have been used in concert with radiolabelled and (super) paramagnetic
      probes to image each phase of the immune response. These probes, which target
      apoptosis, necrosis, neutrophils, monocytes, enzymes, angiogenesis, extracellular
      matrix, and scar formation have been assessed and validated pre-clinically.
      Translating this work to the bedside in a cost-effective, clinically beneficial
      manner remains a significant challenge. This article reviews these new imaging
      techniques as well as the corresponding pathophysiology.

PMID- 24322906
TI  - Relationship of EQ-5D quality of life with the presence of co-morbidity and extra
      articular features in patients with rheumatoid arthritis.
AB  - PURPOSE: Rheumatoid arthritis (RA) is associated with extra-articular features
      (ExRA) and other co-morbidities. The aim of this study is to quantify their
      relative contribution to quality of life (QOL) in patients with RA. METHODS: A
      consecutive series of 114 ambulatory RA patients aged between 40 and 65 years
      were assessed by a research nurse on a single occasion. Assessment included a
      patient questionnaire (including EQ-5D), medication review and fasting venous
      blood sample. Medical records were reviewed by a rheumatologist for co-existing
      conditions. Multiple linear regression was used to adjust mean differences in EQ
      5D in the presence/absence of co-existing conditions for age, sex, university
      education, arthritis duration, rheumatoid factor, erythrocyte sedimentation rate,
      current disease-modifying drug therapy, previous hand joint erosions and joint
      surgery. RESULTS: Mean age was 54 years (82% female) and median arthritis
      duration 10 years. Unadjusted EQ-5D was -0.09 (95% CI -0.18 to -0.01) lower in
      patients with any co-existing condition. EQ-5D scores were inversely correlated
      with the overall number of co-existing conditions (Spearman's rho -0.31, p =
      0.001), number of co-morbidities (rho -0.22, p = 0.02) and number of ExRA
      features (rho -0.22, p = 0.02). There was a linear trend of lower EQ-5D with
      increasing number of co-existing conditions (p = 0.003). EQ-5D was -0.18 (95% CI 
      0.33 to -0.02) lower in the presence of more than two co-existing conditions
      compared to none. Co-morbidity and ExRA features were associated with comparable
      adjusted reductions (-0.05 vs. -0.06) in EQ-5D scores. CONCLUSION: A wide range
      of co-existing conditions are associated with poorer QOL in patients with RA.

PMID- 24322907
TI  - Role of global stress in the health-related quality of life of caregivers:
      evidence from the Survey of the Health of Wisconsin.
AB  - PURPOSE: Informal caregivers play a critical role in the care of individuals who
      are aging or have disabilities and are at increased risk for poor health
      outcomes. This study sought to determine whether and to what extent: (1) global
      stress and health-related quality of life (HRQoL) differed between caregivers and
      non-caregivers; (2) global stress mediated the relationship between caregiving
      status and HRQoL; and (3) caregiver strain (i.e., stress attributable to
      caregiving) was associated with worse HRQoL after accounting for global stress.
      METHODS: Cross-sectional data were from the 2008-2010 Survey of the Health of
      Wisconsin, a representative sample of adults aged 21-74 years. Participants (n =
      1,364) completed questionnaires about caregiving status, sociodemographics,
      global stress, and HRQoL. Staged generalized additive models assessed the impact
      of caregiving on HRQoL and the role of caregiver strain and global stress in this
      relationship. RESULTS: In the last 12 months, 17.2% of the sample reported
      caregiving. Caregivers reported worse mental HRQoL than non-caregivers (beta 
      1.88, p = 0.02); global stress mediated this relationship (p < 0.01). Caregivers
      with the highest levels of strain reported worse mental and physical HRQoL (beta 
      7.12, p < 0.01), and caregivers with the lowest levels of strain reported better
      mental HRQoL (beta 2.06, p = 0.01) than non-caregivers; these associations were
      attenuated by global stress (p < 0.01). CONCLUSION: Global stress, rather than
      caregiving per se, contributes to poor HRQoL among caregivers, above and beyond
      the effect of caregiving strain. Screening, monitoring, and reducing stress in
      multiple life domains presents an opportunity to improve HRQoL outcomes for
      caregivers.

PMID- 24322908
TI  - Impact of hypoalphalipoproteinemia on quality of life in Taiwanese women with
      central obesity.
AB  - PURPOSE: To investigate the relationship between health-related quality of life
      (HRQoL) and different cutoff value of low level of high-density lipoprotein
      cholesterol (HDL-C) in Taiwanese women with different definition of obesity.
      METHODS: Prospective observational study in women with central obesity was
      conducted in Taipei City Hospital. A total of 572 women were screened at our
      clinic, and 227 of them with a body mass index ?27 kg/m2 defined by the
      Department of Health in Taiwan and weight circumference ?80 cm were eligible for
      the study. We defined two groups as group A-low HDL (HDL-C < 40 mg/dL) and group
      B-high HDL (HDL-C < 50 mg/dL) according to different definition of
      hypoalphalipoproteinemia in obese women. RESULTS: Significantly reduced HRQoL
      score was noted in group A-low HDL compared to group A-high HDL (HDL-C ? 40
      mg/dL), but not between group B-low HDL and group B-high HDL (HDL-C ? 50 mg/dL).
      Positively correlation was noted between HDL-C level and physical domain of HRQoL
      score. HDL-C contributes independently to physical domain of HRQoL score after
      controlling for other factors. Decreased leptin and adiponectin level were noted
      in hypoalphalipoproteinemia groups. CONCLUSION: Taiwanese obese women with
      hypoalphalipoproteinemia have adverse impact on HRQoL, especially when the HDL-C
      level is lower than 40 mg/dL. Both hypoalphalipoproteinemia and hypertension
      accounted for a great variance to lower scores of physical domain of HRQoL with
      positively correlation with HDL-C level observed. Decreased leptin and
      adiponectin were also observed in hypoalphalipoproteinemia group, which implied
      increased cardiovascular risk. HDL-C level may deem as another indicator for
      HRQoL in women with central obesity.

PMID- 24322909
TI  - Expert Opinion: which cardiothoracic imaging applications of PET/CT are most
      likely to be replaced by PET/MRI?

PMID- 24322912
TI  - Performance of target irradiation in a high-power laser with a continuous phase
      plate and spectral dispersion.
AB  - We report on the performance of target irradiation at the SG-II high-power laser
      facility with a continuous phase plate (CPP) and the technique of smoothing by
      spectral dispersion (SSD). Simulative and experimental results are presented,
      where the irradiation uniformity and energy concentration of the target spots are
      analyzed. The results show that the designed CPP can focus the spot energy into
      the desired region and shape a profile with steep edge and flat top, but the
      actual performance of the fabricated CPP needs some improvements. It is also
      proved that the CPP is insensitive to the long-scale wavefront distortion in the
      incident beam. The one-dimensional SSD configuration evidently works in smoothing
      the fine-scale intensity modulation inside the target spot. 

PMID- 24322910
TI  - Remodeling and dedifferentiation of adult cardiomyocytes during disease and
      regeneration.
AB  - Cardiomyocytes continuously generate the contractile force to circulate blood
      through the body. Imbalances in contractile performance or energy supply cause
      adaptive responses of the heart resulting in adverse rearrangement of regular
      structures, which in turn might lead to heart failure. At the cellular level,
      cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus;
      (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism.
      Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is
      characterized by reciprocal changes in the expression pattern of "mature" and
      "immature" cardiomyocyte-specific genes. Dedifferentiation may enable
      cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding
      contractile machinery and by reduction of the cellular energy demand.
      Dedifferentiation during myocardial repair might provide cardiomyocytes with
      additional plasticity, enabling survival under hypoxic conditions and increasing
      the propensity to enter the cell cycle. Although dedifferentiation of
      cardiomyocytes has been described during tissue regeneration in zebrafish and
      newts, little is known about corresponding mechanisms and regulatory circuits in
      mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for
      cardiomyocyte dedifferentiation and exerts strong protective effects during
      myocardial infarction highlights the role of cytokines as potent stimulators of
      cardiac remodeling. Here, we summarize the current knowledge about transient
      dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and
      propose a model for the role of OSM in this process. 

PMID- 24322913
TI  - Single-scattering solutions to radiative transfer in infinite turbid media.
AB  - An instantaneous point source generating a light field in an infinite turbid
      medium with anisotropic individual scatterers is considered. Single-scattering
      solutions are sought as the first term of a series expansion of the solution of
      the radiative transfer equation in successive scattering orders. A simple formula
      for a single-scattering solution in media with an arbitrary axially symmetric
      phase function is derived. Applications of this formula are shown for the Henyey
      Greenstein phase function, an ellipsoidal phase function, and a linear phase
      function. In addition, the single-scattering term of the RTE solution derived by
      Kholin [Zh. Vych. Mat. i Mat. Fys.4, 1126 (1964)] for media with a phase function
      represented by a finite series in Legendre polynomials is considered in more
      detail.

PMID- 24322914
TI  - A fast and high-order accurate surface perturbation method for nanoplasmonic
      simulations: basic concepts, analytic continuation and applications.
AB  - In this paper we demonstrate that rigorous high-order perturbation of surfaces
      (HOPS) methods coupled with analytic continuation mechanisms are particularly
      well-suited for the assessment and design of nanoscale devices (e.g., biosensors)
      that operate based on surface plasmon resonances generated through the
      interaction of light with a periodic (metallic) grating. In this connection we
      explain that the characteristics of the latter are perfectly aligned with the
      optimal domain of applicability of HOPS schemes, as these procedures can be shown
      to be the methods of choice for low to moderate wavelengths of radiation and
      grating roughness that is representable by a few (e.g., tens of) Fourier
      coefficients. We argue that, in this context, the method can, for instance,
      produce full and precise reflectivity maps in computational times that are orders
      of magnitude faster than those of alternative numerical schemes (e.g., the
      popular "C-method," finite differences, integral equations or finite elements).
      In this initial study we concentrate on the description of the basic principles
      that underlie the solution scheme, including those that relate to analytic
      continuation procedures. Within this framework, we explain how, in spite of
      conventional wisdom to the contrary, the resulting perturbative techniques can
      provide a most valuable tool for practical investigations in plasmonics. We
      demonstrate this with some examples that have been previously discussed in the
      literature (including treatments of the reflectivity and band gap structure of
      some simple geometries) and extend this to demonstrate the wider applicability of
      the proposed approach. 

PMID- 24322911
TI  - Adiponectin as a tissue regenerating hormone: more than a metabolic function.
AB  - The great interest that scientists have for adiponectin is primarily due to its
      central metabolic role. Indeed, the major function of this adipokine is the
      control of glucose homeostasis that it exerts regulating liver and muscle
      metabolism. Adiponectin has insulin-sensitizing action and leads to down
      regulation of hepatic gluconeogenesis and an increase of fatty acid oxidation. In
      addition, adiponectin is reported to play an important role in the inhibition of
      inflammation. The hormone is secreted in full-length form, which can either
      assemble into complexes or be converted into globular form by proteolytic
      cleavage. Over the past few years, emerging publications reveal a more varied and
      pleiotropic action of this hormone. Many studies emphasize a key role of
      adiponectin during tissue regeneration and show that adiponectin deficiency
      greatly inhibits the mechanisms underlying tissue renewal. This review deals with
      the role of adiponectin in tissue regeneration, mainly referring to skeletal
      muscle regeneration, a process in which adiponectin is deeply involved. In this
      tissue, globular adiponectin increases proliferation, migration and myogenic
      properties of both resident stem cells (namely satellite cells) and non-resident
      muscle precursors (namely mesoangioblasts). Furthermore, skeletal muscle could be
      a site for the local production of the globular form that occurs in an inflamed
      environment. Overall, these recent findings contribute to highlight an intriguing
      function of adiponectin in addition to its well-recognized metabolic action. 

PMID- 24322915
TI  - Analytical expressions for the angle of arrival fluctuations for optical waves'
      propagation through moderate-to-strong non-Kolmogorov refractive turbulence.
AB  - The effects of moderate-to-strong non-Kolmogorov turbulence on the angle of
      arrival (AOA) fluctuations for plane and spherical waves are investigated in
      detail both analytically and numerically. New analytical expressions for the
      variance of AOA fluctuations are derived for moderate-to-strong non-Kolmogorov
      turbulence. The new expressions cover a wider range of non-Kolmogorov turbulence
      strength and reduce correctly to previously published analytic expressions for
      the cases of plane and spherical wave propagation through both weak non
      Kolmogorov turbulence and moderate-to-strong Kolmogorov turbulence cases. The
      final results indicate that, as turbulence strength becomes greater, the
      expressions developed with the Rytov theory deviate from those given in this
      work. This deviation becomes greater with stronger turbulence, up to moderate-to
      strong turbulence strengths. Furthermore, general spectral power law has
      significant influence on the variance of AOA fluctuations in non-Kolmogorov
      turbulence. These results are useful for understanding the potential impact of
      deviations from the standard Kolmogorv spectrum. 

PMID- 24322916
TI  - Physical model of differential Mueller matrix for depolarizing uniform media.
AB  - In this article, we address the question of significance of the parameters of
      differential Mueller matrix formalism. We show how the concept of mean value and
      uncertainty of the optical properties recently introduced to depict this
      differential matrix can be related to the random fluctuations of these optical
      properties. From the layered-medium interpretation introduced by Jones [J. Opt.
      Soc. Am. 38, 671 (1948)] and extended to Mueller-Jones matrix by Azzam [J. Opt.
      Soc. Am. 68, 1756 (1978)], a generalization to depolarizing Mueller matrices is
      proposed. Based on the random Mueller-Jones matrix approach, the obtained
      parameterization perfectly fits the previous results from the literature.
      Necessary conditions of positivity on specific coefficients imposed in order to
      have physical Mueller matrix are introduced in a natural way and not inferred a
      posteriori. Interpretations of the underlying physical processes are also
      presented. An illustrative experimental example is provided from literature data.

PMID- 24322917
TI  - Laser optical feedback imaging controlled by an electronic feedback loop.
AB  - In autodyne interferometry, the beating between the reference beam and the signal
      beam takes place inside the laser cavity and therefore the laser fulfills
      simultaneously the roles of emitter and detector of photons. In these conditions,
      the laser relaxation oscillations play a leading role, both in the laser quantum
      noise, which determines the signal-to-noise ratio (SNR), and also in the laser
      dynamics, which determines the response time of the interferometer. In the
      present study, we have experimentally analyzed the SNR and the response time of a
      laser optical feedback imaging (LOFI) interferometer based on a Nd(3+) microchip
      laser, with a relaxation frequency in the megahertz range. More precisely, we
      have compared the image quality obtained when the laser dynamics is free and when
      it is controlled by a stabilizing electronic feedback loop using a
      differentiator. From this study, we can conclude that when the laser time
      response is shorter (i.e., the LOFI gain is lower), the image quality can be
      better (i.e., the LOFI SNR can be higher) and that the use of an adapted
      electronic feedback loop allows high-speed LOFI with a shot-noise limited
      sensitivity. Despite the critical stability of the electronic feedback loop, the
      obtained experimental results are in good agreement with the theoretical
      predictions.

PMID- 24322918
TI  - Fast and accurate 3D object recognition directly from digital holograms.
AB  - Pattern recognition methods can be used in the context of digital holography to
      perform the task of object detection, classification, and position extraction
      directly from the hologram rather than from the reconstructed optical field.
      These approaches may exploit the differences between the holographic signatures
      of objects coming from distinct object classes and/or different depth positions.
      Direct matching of diffraction patterns, however, becomes computationally
      intractable with increasing variability of objects due to the very high
      dimensionality of the dictionary of all reference diffraction patterns. We show
      that most of the diffraction pattern variability can be captured in a lower
      dimensional space. Good performance for object recognition and localization is
      demonstrated at a reduced computational cost using a low-dimensional dictionary.
      The principle of the method is illustrated on a digit recognition problem and on
      a video of experimental holograms of particles. 

PMID- 24322919
TI  - Least-squares phase estimation with wrapped measurements and branch points.
AB  - A nonorthogonal model for 2D signals with rotational components is presented,
      which enables estimation of phase values from observations of its local
      gradients. In this research, the rotational components are caused by the presence
      of branch points, which indicates phase wrapping. Using the proposed model, the
      phase is estimated using standard least-squares or recently proposed wavelet
      techniques by processing a linear combination of the wrapped observed gradients
      and the curl generated by phase wrapping. 

PMID- 24322920
TI  - Partially coherent stable and spiral beams.
AB  - Stable and spiral coherent beams, which do not change the form of their intensity
      distribution apart from possible scaling and rotation during propagation and
      therefore possess self-healing properties, are widely applied in science and
      technology. On the other hand, it has been found that partially coherent light
      often provides better output than coherent light. Here we consider two methods
      for the design and experimental generation of partially coherent stable and
      spiral beams. 

PMID- 24322921
TI  - Monte Carlo simulation of light scattering in the atmosphere and effect of
      atmospheric aerosols on the point spread function.
AB  - We present a Monte Carlo simulation for the scattering of light in the case of an
      isotropic light source. The scattering phase functions are studied particularly
      in detail to understand how they can affect the multiple light scattering in the
      atmosphere. We show that, although aerosols are usually in lower density than
      molecules in the atmosphere, they can have a non-negligible effect on the
      atmospheric point spread function. This effect is especially expected for ground
      based detectors when large aerosols are present in the atmosphere. 

PMID- 24322922
TI  - Experimental evaluation of speckle suppression efficiency using a moving 2D
      Barker code DOE.
AB  - This paper reports the findings from an experimental evaluation of speckle
      suppression efficiency using a method based on a moving 2D Barker code
      diffractive optical element (DOE). The optical setup and the optical scheme
      parameters of the method are presented. A speckle contrast of ~4.4-5.3% and
      speckle suppression coefficient (coefficient of speckle contrast reduction) of
      k>8 was obtained in experiments. However, the experimentally obtained speckle
      suppression coefficient was approximately 1.5 times smaller than the theoretical
      prediction. It is speculated that the discrepancy between the theoretical and the
      experimental data is due to an inexact match between the optical setup and the
      optimal optical parameters of the method. Analysis of the experimental data
      revealed that once the optical scheme is optimized, it will be possible to obtain
      a speckle suppression that is closer to the theoretical prediction.

PMID- 24322923
TI  - Ultraviolet scattering propagation modeling: analysis of path loss versus range.
AB  - Modeling of the complex atmospheric propagation of deep-ultraviolet (UV)
      radiation is important for applications such as non-line-of-sight (NLOS) UV
      communications. Building upon prior work in which it was observed that short
      range, singly scattered NLOS path loss varies linearly with range, we formalize
      this relationship, generalizing it to consider any order of scattering and more
      general system characteristics. In particular, we derive the approximate
      relationship PL[proportionality]r(2-n) between path loss PL and range r for nth
      order scattered radiation, and investigate the region of validity of this
      approximation. Insight arising from the analysis can be invaluable in the
      development and study of UV systems, as demonstrated by numerical results that
      illustrate implications of the analysis.

PMID- 24322924
TI  - Role of diversity on the singular values of linear scattering operators: the case
      of strip objects.
AB  - The singular value decomposition of the far-zone scattering operator for weak
      strip-like scattering objects is studied under multiple view and/or multiple
      frequency illuminations. The aim is to highlight how such diversities impact the
      number of degrees of freedom (NDF) of the scattering problem. When the angles of
      incidence and/or frequencies vary within discrete finite sets, the singular
      values are analytically determined. It is shown that they exhibit a multistep
      behavior. For the continuous case, upper and lower bounds are found, which allows
      us to obtain estimations for the NDF dependending on the parameters of the
      configuration. 

PMID- 24322925
TI  - Near-field interference of slit doublet.
AB  - We study the physical mechanism of near-field interference of slit doublet and
      explore the distinctive phenomena in near-field interference of slit doublet. The
      average electric field and average energy-flow density are chosen to describe the
      near-field distribution rules of the electromagnetic field. The numerical
      calculations for near-field interference of slit doublet under different
      illumination conditions are performed according to the finite-difference time
      domain method, and the distinctive characteristics of the near-field interference
      of slit doublet are provided. They include the polarization dependence, the
      distortion of fringes, and the bifurcation of the fringes. These characteristics
      are completely different from those of the far-field interference. With the aid
      of the interference of two slits and of slit and groove, the physical mechanism
      of polarization dependence of near-field interference is investigated. The fringe
      distortion of the electric field and the fringe bifurcation of the energy-flow
      density reflect the amplitude and phase variations of the electromagnetic field.
      The influences of the slit parameters and the base material on the near-field
      interference of slit doublet are also discussed. These results may provide us
      with new insights into the underlying physics of interaction between complex
      nanostructures and electromagnetic waves. 

PMID- 24322926
TI  - Transmutation of planar media singularities in a conformal cloak.
AB  - Invisibility cloaking based on optical transformation involves materials
      singularity at the branch cut points. Many interesting optical devices, such as
      the Eaton lens, also require planar media index singularities in their
      implementation. We show a method to transmute two singularities simultaneously
      into harmless topological defects formed by anisotropic permittivity and
      permeability tensors. Numerical simulation is performed to verify the
      functionality of the transmuted conformal cloak consisting of two kissing Maxwell
      fish eyes. 

PMID- 24322927
TI  - Study on the heterodyning scattering of retroreflective free-space optical
      communication with optical heterodyning.
AB  - Retroreflective free-space optical communication is important because of
      advantages such as small volume, low weight, and low power consumption. Link
      failure caused by bad weather conditions will occur because of the attenuated
      retroreflective signal and the increased scattering of the transmitted light. The
      scattering effect can be reduced because the physical properties (including
      polarization, wavefront, and phase) of the scattering signal are different from
      those of the retroreflective signal. The physical properties of the scattering
      signal are obtained using a polarization-sensitive Monte Carlo model, and the
      heterodyning scattering signal is obtained using heterodyning theory. Results
      show that, with optical heterodyning, the scattering effect is efficiently
      reduced, and advantages such as better adaptability to bad weather conditions,
      longer communication range, more compact transceiver design, larger covering area
      of the optical receiver, and easier target acquisition for the retromodulator
      than before can also be obtained. 

PMID- 24322928
TI  - Poincare sphere mapping by Mueller matrices.
AB  - By using the symmetric serial decomposition of a normalized Mueller matrix M [J.
      Opt. Soc. Am. A 26, 1109 (2009)] as a starting point and by considering the
      reciprocity property of Mueller matrices, the geometrical features of the
      Poincare sphere mapping by M are analyzed in order to obtain a new
      parameterization of M in which the 15 representative parameters have
      straightforward geometrical interpretations. This approach provides a new
      geometry-based framework, whereby any normalized Mueller matrix M is completely
      described by a set of three associated ellipsoids whose geometrical and
      topological properties are characteristic of M. The mapping analysis considers
      the cases of type-I and type-II, as well as singular and nonsingular Mueller
      matrices. The novel parameterization is applied to several illustrative examples
      of experimental Mueller matrices taken from the literature.

PMID- 24322929
TI  - State of polarization and propagation factor of a stochastic electromagnetic beam
      in a gradient-index fiber.
AB  - With the help of a tensor method, we investigate the evolution properties of the
      state of polarization of an electromagnetic Gaussian Schell-model beam
      propagating through a gradient-index (GRIN) fiber. We find that the Stokes
      parameters and the polarization ellipse exhibit periodicity. The initial beam
      parameters affect the values of the Stokes parameters and the parameters of the
      polarization ellipse. Furthermore, based on the second-order moments of the
      Wigner distribution function, the explicit expression for the propagation factor
      (known as the M(2) factor) in the GRIN fiber is derived. It is shown that the
      M(2) factor remains invariant on propagation and is determined only by the
      initial beam parameters.

PMID- 24322930
TI  - Maximizing band gaps in two-dimensional photonic crystals in square lattices.
AB  - This paper is devoted to a numerical algorithm for the maximization of band gaps
      in two-dimensional photonic crystals in square lattices. We first apply the
      finite element method to solve the eigenvalue problem, then use the piecewise
      constant level set (PCLS) method to maximize the band gaps. The PCLS method is
      very powerful for representing and modeling regions of different structures.
      Extremely large gaps are realized with gallium arsenide material, for transverse
      magnetic field (TM), transverse electric field (TE), and for complete band gaps.
      When the mean gap frequency is below 1, the biggest gap is about 0.2922 for the
      TE. 

PMID- 24322931
TI  - Multiple scattering of arbitrarily incident Bessel beams by random discrete
      particles.
AB  - In this paper, we introduce an efficient numerical method to characterize the
      multiple scattering by random discrete particles illuminated by Bessel beams with
      arbitrary incidence. Specifically, the vector expressions of Bessel beams that
      perfectly satisfy Maxwell's equations in combination with rotation Euler angles
      are used to represent the arbitrarily incident Bessel beams. A hybrid vector
      finite element-boundary integral-characteristic-basis function method is utilized
      to formulate the scattering problems involving multiple discrete particles with a
      random distribution. Due to the flexibility of the finite element method, the
      adopted method can conveniently deal with the problems of multiple scattering by
      randomly distributed homogeneous particles, inhomogeneous particles, and
      anisotropic particles. Some numerical results are included to illustrate the
      validity and capability of the proposed method and to show the scattering
      behaviors of random discrete particles when they are illuminated by Bessel beams.

PMID- 24322932
TI  - Spatial-resolution analysis and optimal design of integral imaging.
AB  - Integral imaging is a promising technology for 3D imaging and display. This paper
      reports the 3D spatial-resolution research based on reconstructed 3D space.
      Through geometric analysis of the reconstructed optical distribution from all the
      element images that attend recording, the relationship among microlens
      parameters, planar-recording resolution, and 3D spatial resolution was obtained.
      The effect of microlens parameter accuracy on the reconstructed position error
      also was discussed. The research was carried on the depth priority integral
      imaging system (DPII). The results can be used in the optimal design of integral
      imaging. 

PMID- 24322933
TI  - Perfect imaging with planar interfaces.
AB  - We describe the most general homogenous, planar, light-ray-direction-changing
      sheet that performs one-to-one imaging between object space and image space. This
      is a nontrivial special case (of the sheet being homogenous) of an earlier result
      [Opt. Commun.282, 2480 (2009)]. Such a sheet can be realized, approximately, with
      generalized confocal lenslet arrays. 

PMID- 24322934
TI  - Turbulence distance for laser beams propagating through non-Kolmogorov
      turbulence.
AB  - Based on the second-order moments and the non-Kolmogorov turbulence spectrum, the
      general analytical expression for the turbulence distance of laser beams
      propagating through non-Kolmogorov turbulence is derived, which depends on the
      non-Kolmogorov turbulence parameters including the generalized exponent parameter
      alpha, inner scale l(0), and outer scale L(0) and the initial second-order
      moments of the beams at the plane of z=0. Taking the partially coherent Hermite
      Gaussian linear array (PCHGLA) beam as an illustrative example, the effects of
      non-Kolmogorov turbulence and array parameters on the turbulence distance are
      discussed in detail. The results show that the turbulence distance z(Mx)(alpha)
      of PCHGLA beams through non-Kolmogorov turbulence first decreases to a dip and
      then increases with increasing alpha, and the value of z(Mx)(alpha) increases
      with increasing beam number and beam order and decreasing coherence parameter,
      meaning less influence of non-Kolmogorov turbulence on partially coherent array
      beams than that of fully coherent array beams and a single partially coherent
      beam. However, the value of z(Mx)(alpha) for PCHGLA beams first increases
      nonmonotonically with the increasing of the relative beam separation x0' for
      x0'<=1 and increases monotonically as x0' increases for x0'>1. Moreover, the
      variation behavior of the turbulence distance with the generalized exponent
      parameter, inner scale, and outer scale of the turbulence and the beam number is
      similar, but different with the relative beam separation for coherent and
      incoherent combination cases.

PMID- 24322935
TI  - Waveguide-coupled nanowire as an optical antenna.
AB  - We study the optical coupling between a gold nanowire and a silver ion-exchanged
      waveguide, with special emphasis on the nanowire antenna radiation pattern. We
      measure the radiation patterns of waveguide-coupled gold nanowires with a height
      of 70 nm and width of 50 or 150 nm in the 450-700 nm spectral range for TE and TM
      polarizations. We perform a systematic theoretical study on the wavelength,
      polarization, nanowire size, and material dependences on the properties of the
      radiation pattern. We also give some elements concerning absorption and near
      field. Experiments and calculations show localized plasmon resonance for the
      polarization orthogonal to the wire (far-field resonance at 580 nm for the
      smallest wire and 670 nm for the widest). It is shown that a great variety of
      radiation patterns can be obtained, together with a high sensitivity to a change
      of one parameter, particularly near-resonance. 

PMID- 24322936
TI  - Transmission resonances in a metal film with arrays of asymmetry cross-shaped
      apertures.
AB  - We studied numerically the transmission properties of the periodic array of
      asymmetric cross-shaped apertures in an Ag film. The relative positions of the
      two orthogonally oriented rectangular apertures are varied, rather than their
      length or width. Each transmission peak of the original symmetric cross-shaped
      apertures will split into two peaks in the case of the asymmetric cross-shaped
      apertures when the electric field is perpendicular to the long axis of the
      unchanged rectangular aperture. The wavelength of the shift peak has a linear
      relation with the asymmetry. This resonance response mainly results from the
      excitation of the trapped mode provided by the structural symmetry breaking. A
      distribution of the magnetic field and a simple Lagrange model are used to
      interpret these phenomena. In addition, the intensity of the transmission peaks
      can be tuned by changing the incident polarization angle. 

PMID- 24322937
TI  - Intermodal energy transfer in a tapered optical fiber: optimizing transmission.
AB  - We present an experimental and theoretical study of the energy transfer between
      modes during the tapering process of an optical nanofiber through spectrogram
      analysis. The results allow optimization of the tapering process, and we measure
      transmission in excess of 99.95% for the fundamental mode. We quantify the
      adiabaticity condition through calculations and place an upper bound on the
      amount of energy transferred to other modes at each step of the tapering, giving
      practical limits to the tapering angle. 

PMID- 24322938
TI  - Microcellular propagation prediction model based on an improved ray tracing
      algorithm.
AB  - Two-dimensional (2D)/two-and-one-half-dimensional ray tracing (RT) algorithms for
      the use of the uniform theory of diffraction and geometrical optics are widely
      used for channel prediction in urban microcellular environments because of their
      high efficiency and reliable prediction accuracy. In this study, an improved RT
      algorithm based on the "orientation face set" concept and on the improved 2D
      polar sweep algorithm is proposed. The goal is to accelerate point-to-point
      prediction, thereby making RT prediction attractive and convenient. In addition,
      the use of threshold control of each ray path and the handling of visible grid
      points for reflection and diffraction sources are adopted, resulting in an
      improved efficiency of coverage prediction over large areas. Measured results and
      computed predictions are also compared for urban scenarios. The results indicate
      that the proposed prediction model works well and is a useful tool for
      microcellular communication applications. 

PMID- 24322939
TI  - Improving the performance of image classification by Hahn moment invariants.
AB  - The discrete orthogonal moments are powerful descriptors for image analysis and
      pattern recognition. However, the computation of these moments is a time
      consuming procedure. To solve this problem, a new approach that permits the fast
      computation of Hahn's discrete orthogonal moments is presented in this paper. The
      proposed method is based, on the one hand, on the computation of Hahn's discrete
      orthogonal polynomials using the recurrence relation with respect to the variable
      x instead of the order n and the symmetry property of Hahn's polynomials and, on
      the other hand, on the application of an innovative image representation where
      the image is described by a number of homogenous rectangular blocks instead of
      individual pixels. The paper also proposes a new set of Hahn's invariant moments
      under the translation, the scaling, and the rotation of the image. This set of
      invariant moments is computed as a linear combination of invariant geometric
      moments from a finite number of image intensity slices. Several experiments are
      performed to validate the effectiveness of our descriptors in terms of the
      acceleration of time computation, the reconstruction of the image, the
      invariability, and the classification. The performance of Hahn's moment
      invariants used as pattern features for a pattern classification application is
      compared with Hu [IRE Trans. Inform. Theory 8, 179 (1962)] and Krawchouk [IEEE
      Trans. Image Process.12, 1367 (2003)] moment invariants.

PMID- 24322940
TI  - Vortex structure of elegant Laguerre-Gaussian beams of fractional order.
AB  - The transition of the vortex structure of fractional elegant Laguerre-Gaussian
      beams is discussed in detail as the angular mode index of the beam is
      continuously varied between integer values. Under this kind of variation, the
      vortices can be classified into five groups. Contrary to the behavior of the
      vortices of the nondiffracting Bessel beams of fractional order, the nodal lines
      of the vortices in the case of the fractional eLG beams exhibit intricate shapes.

PMID- 24322942
TI  - Influence study of solving correction forces caused by fitting errors for thin
      meniscus mirror.
AB  - The actuator influence functions of a thin meniscus mirror can be expanded in
      Zernike polynomials. And the correctness of influence functions has a great
      effect on solving the correction forces. The Zernike coefficients are applied as
      parameters in the all-floating support system. We analyze the main interferential
      factors when different deformation modes are corrected. The influence caused by
      fitting errors is studied in this paper. A preferable result can be obtained
      after eliminating the interferential factors. The method can obtain useful
      correction forces. Comparing the peak-to-valley and root mean square values among
      the results calculated by different accuracy influence functions, we find that
      there is a limited convergence property when the accuracy increases. 

PMID- 24322941
TI  - Modeling lateral geniculate nucleus response with contrast gain control. Part 1:
      formulation.
AB  - A class of models for lateral geniculate nucleus (LGN) on-cell behavior is
      proposed. The models consist of a linear filter with divisive normalization by
      root mean square local contrast and include an intrinsic noise density parameter.
      The properties of these models are shown to match observed LGN behavior: (1) a
      linear response to low-magnitude stimuli; (2) a linear response without
      saturation (luxotonic behavior) for zero-contrast stimuli (homogeneous fields)
      with increasing magnitude; and (3) response saturation for nonzero contrast
      stimuli with increasing magnitude. The models possess an intrinsic scale for
      signal-to-noise ratio (SNR). The models show under and supersaturation, as well
      as saturation, for sinusoidal grating stimuli with increasing contrast and
      predict that different SNR regimes will cause a single neuron to show different
      contrast response curves. A companion paper [1] provides a detailed analysis of
      the full nonlinear response for sinusoidal grating stimuli and circular spot
      stimuli.

PMID- 24322944
TI  - Determination of the rough interface parameters using the self-imaging effect.
AB  - In this work, a linear grating is used to project a periodic light intensity
      distribution on a rough interface, and the near field transmitted light
      scattering is studied. It is shown theoretically that the intensity in the
      Fresnel regime depends on statistical properties of the rough interface and the
      light intensity period. The self-image contrast exponentially depends on the
      interface height-height correlation function. The correlation is obtained in
      terms of multiplication of the self-image number and the period of the light
      intensity distribution. Therefore, the roughness and the correlation length of
      the interface can be obtained by determining the contrast of the self-images when
      the light intensity period is smaller than the interface correlation length. For
      periods longer than twice the correlation length, the contrast measurements only
      provide the interface roughness. In experimental studies, the roughness of
      interfaces is determined by square gratings with periods much longer than the
      correlation lengths. The rough interfaces are prepared by roughening sheet glass
      by powders of different grit numbers. The results for different gratings and
      light wavelengths are quite consistent. 

PMID- 24322945
TI  - Channelized model observer for the detection and estimation of signals with
      unknown amplitude, orientation, and size.
AB  - As a task-based approach for medical image quality assessment, model observers
      (MOs) have been proposed as surrogates for human observers. While most MOs treat
      only signal-known-exactly tasks, there are few studies on signal-known
      statistically (SKS) MOs, which are clinically more relevant. In this paper, we
      present a new SKS MO named channelized joint detection and estimation observer
      (CJO), capable of detecting and estimating signals with unknown amplitude,
      orientation, and size. We evaluate its estimation and detection performance using
      both synthesized (correlated Gaussian) backgrounds and real clinical (magnetic
      resonance) backgrounds. The results suggest that the CJO has good performance in
      the SKS detection-estimation task. 

PMID- 24322946
TI  - Coherent-mode representation of partially polarized pulsed electromagnetic beams.
AB  - Coherent-mode representation provides physical insight and computational
      simplification into the analysis of random optical signals. In this work, we
      present the coherent-mode decomposition for pulsed electromagnetic beam fields.
      We show that the mode decomposition can be done for any valid space-frequency or
      space-time coherence matrix representing nonstationary pulsed electric field, and
      moreover, the spectral and temporal modes are connected via a Fourier transform
      relation. The analysis also yields the coherent modes of electromagnetic time
      domain signals in temporal optics. We present the overall degree of coherence as
      a measure of the average temporal or spectral and spatial coherence of the beam.
      Several illustrative examples are discussed analytically and numerically. 

PMID- 24322947
TI  - Link functions and Matern kernel in the estimation of reflectance spectra from
      RGB responses.
AB  - We evaluate three link functions (square root, logit, and copula) and Matern
      kernel in the kernel-based estimation of reflectance spectra of the Munsell Matte
      collection in the 400-700 nm region. We estimate reflectance spectra from RGB
      camera responses in case of real and simulated responses and show that a
      combination of link function and a kernel regression model with a Matern kernel
      decreases spectral errors when compared to a Gaussian mixture model or kernel
      regression with the Gaussian kernel. Matern kernel produces performance similar
      to the thin plate spline model, but does not require a parametric polynomial part
      in the model. 

PMID- 24322948
TI  - Recommendations for the use of new oral anticoagulants (NOACs) after TIA or
      stroke caused by atrial fibrillation (AF), after a consensus conference among
      Italian neurologists (the Venice group).
AB  - Vascular neurologists of Veneto and Friuli Venezia Giulia, north-east regions of
      Italy, have sought an agreement on the two following questions: (A) what
      prophylactic treatment should we recommend to patients with a stroke ascribed to
      atrial fibrillation (AF), who were not previously on antithrombotic treatment, to
      prevent further strokes? (B) What should we do in the event of an ischemic or
      hemorrhagic stroke associated with AF in patients who were already on
      antithrombotic treatment? There was a unanimous consensus for preferring the new
      oral anticoagulants (NOACs) in patients not taking any antithrombotics and in
      cases treated with antithrombotic drugs (coumadin and/or antiplatelets), due to a
      lower incidence of intracranial bleeding complications and a noninferiority for
      recurrent stroke or TIA. Even after intracranial bleeding complications, when it
      is useful or necessary to continue anticoagulant treatment, the group of experts
      preferred the NOACs, suggesting, however, to be very cautious in cases with
      widespread leukoaraiosis or microbleeds, practice frequent monitoring of
      creatinine clearance (CrCl) and avoid using NOACs when CrCl is <30 mL/min.

PMID- 24322949
TI  - Prevalence and predictors of depression in Iranian patients with multiple
      sclerosis: a population-based study.
AB  - Depression is a frequent symptom in multiple sclerosis (MS) which has a negative
      impact on quality of life and cognitive status. The purpose of this study was to
      determine the prevalence and associated factors of depression, and status of
      antidepressant use in Iranian MS patients. One-hundred and sixty patients with
      definite MS were included. Demographic and clinical characteristics were
      recorded. Fatigue and depression were evaluated using the fatigue severity scale
      and Beck depression inventory-II. Cognitive performance and disability were
      examined by mini-mental status examination and expanded disability status scale.
      Multiple logistic regressions were used to determine the associated factors of
      depression and antidepressant use. The prevalence of depression and severe
      depression was 59.4 and 18.1 %, respectively. However, only 21.1 % of patients
      were on antidepressant treatment, while the prevalence of unrecognized/untreated
      depression was found to be as high as 44.1 %. Multivariable analysis showed that
      fatigue (P < 0.0001, OR = 5.98, 95 % CI = 2.9-12.3) and older age (P = 0.027, OR
      = 2.24, 95 % CI = 1.09-4.6) were associated with depression in MS patient. A
      significant association was found between fatigue and antidepressant use (P =
      0.001, OR = 6.81, 95 % CI = 2.26-20.48). Our findings demonstrate that depression
      is significantly associated with fatigue and older age, regardless of other
      factors. Moreover, despite the high prevalence of depression in MS, most patients
      do not receive adequate treatment.

PMID- 24322950
TI  - Giant cell arteritis with symptomatic intracranial stenosis and endovascular
      treatment.

PMID- 24322951
TI  - Tarlov cysts: clinical evaluation of an Italian cohort of patients.

PMID- 24322953
TI  - Safety planning in focus groups of Malawian women living with HIV: helping each
      other deal with violence and abuse.
AB  - In this critical ethnography, 72 HIV-infected women in Southern Malawi
      participated in 12 focus groups discussing the impact of HIV and violence. Our
      analysis, informed by a postcolonial feminist perspective, revealed women's
      capacity to collectively engage in safety planning. We present our findings about
      women's experiences based on narratives detailing how women collectively
      strategized safety planning efforts to mitigate the impact of violence. This
      study helps to fill a gap in the literature on the intersection between HIV and
      violence in women's lives. Strategies discussed by the women could form a basis
      for safety planning interventions for women in similar circumstances. 

PMID- 24322954
TI  - Pediatric injuries associated with high chairs and chairs in the United States,
      2003-2010.
AB  - This study describes the epidemiology of injuries among children <=3 years old
      associated with high chairs compared with chairs by retrospectively analyzing
      data from the National Electronic Injury Surveillance System from 2003 to 2010.
      An estimated 402 479 (95% confidence interval = 335 116-469 842) injuries
      associated with high chairs and chairs were treated in United States emergency
      departments, with an average of 9421 high chair-related injuries and 40 889 chair
      related injuries annually. The number of high chair-related injuries
      significantly increased by 22.4% from 8926 injuries in 2003 to 10 930 injuries in
      2010. Falling was the most common injury mechanism associated with high chairs
      (92.8%) and chairs (87.3%). Closed head injury was the most common diagnosis
      associated with high chairs (37.3%), and increased in number (P = .005) and rate
      (P = .006) from 2003 to 2010. Child caregivers should properly engage high chair
      safety restraint systems and encourage appropriate behaviors by young children
      when using chairs.

PMID- 24322955
TI  - Differences in blood pressure monitoring for children and adolescents with
      hypertension among pediatric cardiologists and pediatric nephrologists.

PMID- 24322956
TI  - Physicians' assurances of confidentiality and time spent alone with adolescents
      during primary care visits.

PMID- 24322957
TI  - Neck masses in children.

PMID- 24322958
TI  - Back pain in a patient with common variable immunodeficiency.

PMID- 24322960
TI  - Living in an older adult community: a pharmacy student's experience.
AB  - Interacting with older adults is a daily practice for pharmacists. It is
      important to understand how medications affect their wellbeing, but there are
      many other factors that affect quality of life. To truly understand some of the
      challenges facing older adults, Emily Anastasia, a sixth-year pharmacy student at
      the University of Rhode Island, moved into South Bay Retirement Living, a senior
      living community, for an eight-day immersion experience as a special project
      within one of her advanced pharmacy practice experience rotations. During her
      stay, she did not attend classes nor leave the facility unless on the South Bay
      bus with the other assisted living residents. She lived with a 92-year-old
      roommate, developed close friendships with many of the residents, and kept a
      detailed journal of her experience. The purpose of this reflection is to share
      her experience and recognize lifestyle as well as social and physical environment
      as factors in understanding the aging process. Immersing a pharmacy student
      within an assisted living community provides a unique opportunity to observe and
      appreciate characteristics of older adults that cannot be learned within a
      classroom setting. 

PMID- 24322961
TI  - Evaluation of a pharmacy-driven inpatient discharge counseling service: impact on
      30-day readmission rates.
AB  - OBJECTIVE: To evaluate the impact of a pharmacy-driven inpatient discharge
      counseling service on 30-day readmission rates. DESIGN: A retrospective
      electronic chart review was performed comparing internal medicine patients who
      received pharmacy discharge counseling with those who received the standard
      discharge process between May 1, 2011, and March 28, 2012. SETTING: A community
      teaching hospital's internal medicine service. PATIENTS: A total of 1,536
      patients discharged from the internal medicine service were eligible for study
      inclusion. A total of 228 of these patients received pharmacy discharge
      counseling. INTERVENTIONS: Patients were screened for readmission risk. For those
      patients who scored as high risk, an attempt was made to provide pharmacy
      counseling and a discharge medication list. MAIN OUTCOMES MEASURES: The primary
      endpoint was to evaluate whether pharmacy discharge counseling had an impact on
      readmission rates. An additional outcome was to measure the quantity of pharmacy
      interventions. RESULTS: Out of the 228 patients who received pharmacy discharge
      counseling, 18.9% were readmitted within 30 days of hospital discharge, which was
      similar to the readmission rate for high- and moderate-risk patients who did not
      receive counseling (18.8% and 18.9%, respectively). But, after stratification
      based on readmission risk, the moderate-risk, pharmacy-counseled group had a
      significantly lower readmission rate than the moderate-risk control group (3.8%
      vs. 18.9%; P=0.033). Overall, 915 pharmacist interventions were made, averaging 4
      interventions per patient. CONCLUSIONS: Pharmacy discharge counseling was
      associated with reduced 30-day readmission rates in those patients at moderate
      risk for readmission.

PMID- 24322962
TI  - Impact of pharmacy intervention on the use of proton-pump inhibitors in the
      hospital setting.
AB  - OBJECTIVE: Determine effectiveness of pharmacy-driven medical staff training
      regarding proton-pump inhibitor (PPI) therapy. DESIGN: This study was performed
      in two parts. Part I evaluated baseline PPI usage within the hospital. Part II
      evaluated the effect of pharmacy-driven medical staff education on PPI
      prescribing patterns. Data were collected retrospectively via electronic chart
      review. SETTING: Passavant Area Hospital in Jacksonville, Illinois, is a 99-bed
      community hospital. PARTICIPANTS: Patients' profiles were selected if
      administration of at least one PPI was electronically charted during their
      hospital stay. Patients discharged from the emergency department were not
      included in the study. There were a total of 1,089 charts reviewed (Part I:
      N=565; Part II: N=524). The average patient age was 66.5 years. INTERVENTIONS:
      Part I results were presented to the pharmacy and therapeutics (P&T) committee
      and medical staff. A series of three educational presentations were subsequently
      given to medical staff. Part II results were reported to the P&T committee, with
      further interventions to be determined after consulting with hospital
      administration and medical staff. MAIN OUTCOME MEASURE: Improvement of
      appropriate acute PPI therapy. Secondary outcome measures included duration of
      acute therapy and continuation of chronic therapy. RESULTS: There was improvement
      in the appropriate usage of PPI for stress ulcer prophylaxis (SUP) (P=0.1216),
      decreased chronic PPI therapy (P=0.0054), and increased documentation of PPI
      indication (P=0.0365). A decrease of appropriate acute duration of PPI for SUP
      was also observed (P<0.0001). CONCLUSIONS: Appropriate initiation of acute and
      continuation of chronic PPI therapies improved. Appropriate duration of use
      declined in SUP patients. Pharmacy interventions have an overall positive impact
      on appropriate use of PPI therapy.

PMID- 24322963
TI  - Effects of health literacy and polypharmacy on medication adherence.
AB  - OBJECTIVE: To determine if health literacy has an effect on medication adherence
      in patients taking fewer than five prescriptions (no polypharmacy), and those
      taking five or more prescriptions (polypharmacy). DESIGN: Retrospective cohort.
      SETTING: The Primary Care Residents' Clinic at Virginia Commonwealth University
      Health System (VCUHS). PATIENTS: Those who received a Rapid Estimate of Adult
      Literacy in Medicine-Revised (REALM-R) assessment at the clinic between June 1,
      2009, and June 30, 2010, and utilized the VCUHS outpatient pharmacies to fill
      their prescriptions. A total of 648 individuals were identified. INTERVENTIONS:
      The degree of health literacy and level of medication adherence were analyzed per
      patient by accessing the clinic's electronic health records. The number of
      medications each patient filled was determined using VCUHS outpatient pharmacy
      databases. MAIN OUTCOME MEASURE: To determine if there are any associations among
      the degree of health literacy, the level of medication adherence, and the amount
      of medications a patient is taking. RESULTS: There was a significant association
      found between the level of medication adherence and the degree of polypharmacy.
      We found no association between the degree of health literacy and the level of
      adherence to a prescribed medication regimen. Additionally, there was no
      relationship between the degree of polypharmacy and health literacy. Those
      patients with more medications were also found to have lower levels of medication
      adherence and vice versa. CONCLUSION: Our study does not show an association
      between health literacy and medication adherence nor between health literacy and
      polypharmacy. Thus, potential changes to improving health literacy may not have a
      significant effect on adherence.

PMID- 24322964
TI  - Donepezil 23 mg: a brief insight on efficacy and safety concerns.
AB  - As life expectancy increases, it is imperative that health care providers
      recognize the importance of safe medication use within an aging geriatric
      population. Dealing with a cohort that has different biological and medical
      demands requires pharmacists to pay particular attention to details when treating
      this subset of individuals. In particular, this manuscript will focus on
      Alzheimer's disease (AD) and considerations when dealing with new treatment
      options. The Food and Drug Administration's recent approval of the increased
      dosage strength, donepezil 23 mg, previously only available in 5 mg and 10 mg
      strengths, has raised efficacy and safety concerns. Reservations stem from
      unproven superiority along with an increased incidence of adverse events. The
      purpose of the manuscript is to provide a brief insight into these concerns and
      provide readers the knowledge necessary to make a clinically sound decision when
      treating patients with moderate-to-severe AD. 

PMID- 24322965
TI  - Stepwise addition of difluorocarbene to a transition metal centre.
AB  - The Ruppert-Prakash reagent (Me3SiCF3) is used to introduce difluorocarbene (CF2)
      and tetrafluoroethylene (TFE) ligands to cobalt(I) metal centres, whereby the TFE
      ligand is generated via [2+1] cycloaddition between [Co]=CF2 and CF2.

PMID- 24322966
TI  - The quality of outpatient antimicrobial prescribing: a comparison between two
      areas of northern and southern Europe.
AB  - PURPOSE: The aim of the study was to analyse and compare the quality of
      outpatient antimicrobial prescribing in Denmark and Aragon (in northeastern
      Spain), with the objective of assessing inappropriate prescribing. METHODS:
      Outpatient antimicrobial prescription data were obtained from the National
      Institute for Health Data and Disease Control in Denmark, and from the Aragon
      Information System of Drug Consumption. The number of Defined Daily Doses (DDD)
      of the different substances were calculated, and the quality of the antimicrobial
      prescription was analysed using the 'Drug Utilization 90 %' method and the
      European Surveillance of Antimicrobial Consumption (ESAC) quality indicators for
      outpatient antimicrobial use. RESULTS: The majority of the prescriptions (90 % of
      total DDD) were comprised of 14 (of 39) different antimicrobials in Denmark,
      based mainly on narrow spectrum penicillin, and 11 (of 59) antimicrobials in
      Aragon, principally broad spectrum penicillins. The quality indicators described
      an elevated consumption of antimicrobials and an important seasonal variation in
      Aragon. In Denmark, the values obtained reflected a more moderate use with minor
      seasonal variation. CONCLUSIONS: The results showed important differences between
      the two study areas in relation to quantity and quality of outpatient
      antimicrobial prescription. The data indicate an overuse (and/or misuse) of
      antimicrobials in the Spanish region, despite national and local guidelines. The
      pattern of prescription in Denmark reflects a better adherence to
      recommendations.

PMID- 24322967
TI  - HCP5 genetic variant (RS3099844) contributes to Nevirapine-induced Stevens
      Johnsons Syndrome/Toxic Epidermal Necrolysis susceptibility in a population from
      Mozambique.
AB  - PURPOSE: Nevirapine (NVP) is an anti-retroviral drug used for the treatment of
      HIV infection, that may cause several severe adverse events, including Stevens
      Johnsons Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). A recent whole genome
      association study highlighted a strong association with allopurinol-induced
      SJS/TEN within the HCP5 and PSORS1C1 genes in the Japanese population. Our aim
      was to verify the contribution of these two genes in the susceptibility to NVP
      induced SJS/TEN in a population from Mozambique. METHODS: Genotyping of PSORS1C1
      rs2233945 and HCP5 rs3099844 SNPs was performed in a sample of 27 patients with
      SJS/TEN and 76 controls. A case-control and a haplotype analysis were performed.
      RESULTS: The HCP5 rs3099844 variant allele was significantly associated with the
      SJS/TEN susceptibility (OR = 2.03 and P = 0.039). The TA haplotype, carrying both
      the variant alleles of the two genes, showed a higher risk for developing SJS/TEN
      (OR = 3.44and P = 0.003). The regression analysis confirmed the contribution of
      HCP5 rs3099844 SNP (OR = 2.05, P = 0.047). By a log-linear model, we also
      investigated for interaction between HCP5 rs309844 and PSORS1C1 rs2233945 SNPs
      with respect to SJS/TEN risk, and we observed a strong interaction between the
      two SNPs (P = 0.005). CONCLUSIONS: We confirmed the association of HCP5 with the
      SJS/TEN susceptibility in a population from Mozambique treated with NVP.

PMID- 24322968
TI  - Proximal intracranial arterial occlusions: does the natural history justify
      further interventional trials?

PMID- 24322969
TI  - Dependence of optical attenuation coefficient and mechanical tension of
      irradiated human cartilage measured by optical coherence tomography.
AB  - As banked human tissues are not widely available, the development of new non
      destructive and contactless techniques to evaluate the quality of allografts
      before distribution for transplantation is very important. Also, tissues will be
      processed accordingly to standard procedures and to minimize disease transmission
      most tissue banks will include a decontamination or sterilization step such as
      ionizing radiation. In this work, we present a new method to evaluate the
      internal structure of frozen or glycerol-processed human cartilages, submitted to
      various dosis of irradiation, using the total optical attenuation coefficient
      retrieved from optical coherence tomography (OCT) images. Our results show a
      close relationship between tensile properties and the total optical attenuation
      coefficient of cartilages. Therefore, OCT associated with the total optical
      attenuation coefficient open a new window to evaluate quantitatively biological
      changes in processed tissues. 

PMID- 24322970
TI  - A continuum of approaches toward developing culturally focused prevention
      interventions: from adaptation to grounding.
AB  - The purpose of this article is to describe a conceptual model of methods used to
      develop culturally focused interventions. We describe a continuum of approaches
      ranging from non-adapted/surface-structure adapted programs to culturally
      grounded programs, and present recent examples of interventions resulting from
      the application of each of these approaches. The model has implications for
      categorizing culturally focused prevention efforts more accurately, and for
      gauging the time, resources, and level of community engagement necessary to
      develop programs using each of the different methods. The model also has
      implications for funding decisions related to the development and evaluation of
      programs, and for planning of participatory research approaches with community
      members. 

PMID- 24322971
TI  - Cardiovascular pharmacogenomics: expectations and practical benefits.
AB  - Cardiovascular disease is a leading cause of morbidity and mortality worldwide.
      Pharmacogenomics is the study of genetic determinants of interindividual
      variation in drug response and aims to facilitate personalized medicine, through
      genotype-informed drug and dose selection, to maximize drug efficacy and/or
      minimize adverse drug reactions. Despite high expectations, no cardiovascular
      pharmacogenomic association is currently in widespread clinical practice;
      evidential, logistical, financial, and knowledge implementation barriers exist.
      Nevertheless, VKORC1, CYP2C9, and CYP4F2 variants have been associated with
      warfarin dose requirements, and CYP2C19 variants have been associated with
      perturbed antiplatelet response to clopidogrel. However, at present, controversy
      exists over the clinical utility of these genetic associations. There is an
      increased risk of simvastatin-induced muscle toxicity in SLCO1B1*5 carriers,
      ADRB1 and ADRA2C polymorphisms are associated with differential response to
      bucindolol, and rare congenital arrhythmia gene variants have been identified in
      drug-induced torsade de pointes. Practical benefits are still anticipated, but
      much work remains. 

PMID- 24322975
TI  - Cardiovascular disease in CKD in 2013: Reducing cardiovascular risk--light at the
      end of the tunnel.
AB  - During 2013, a meta-analysis provided evidence that cystatin C improves estimated
      glomerular filtration rate in cardiovascular risk categorization in chronic
      kidney disease (CKD). Another study showed that low diastolic blood pressure
      (DBP) is harmful in patients with CKD, challenging the paradigm of treating
      elevated systolic blood pressure regardless of DBP. Overall, mortality rates in
      CKD have decreased but further improvement is required.

PMID- 24322977
TI  - Genetics: Causative genes identified in rare renal ciliopathies.

PMID- 24322978
TI  - Vocoder simulations of highly focused cochlear stimulation with limited dynamic
      range and discriminable steps.
AB  - OBJECTIVES: There is recent interest in focused stimulation of the cochlea via
      modalities such as tripolar electrical and infrared neural stimulation to improve
      speech in noise comprehension and music perception. The purpose of this work was
      to use vocoder-based simulations to investigate speech recognition for broad
      stimulation (standard monopolar paradigm) versus more focused stimulation under a
      variety of signal-to-noise ratios, dynamic ranges, and numbers of discriminable
      loudness steps. DESIGN: Vocoder simulations were used to assess the
      intelligibility of sentences, consonants, and vowels that were noise vocoded and
      presented to 7 normal-hearing listeners for identification. A novel aspect of the
      simulations presented here was the use of nonuniform quantization steps within
      the dynamic range to more closely simulate the Weber functions observed in
      cochlear implant users. Intelligibility was assessed for the different filter
      slopes under a variety of signal-to-noise ratio levels, dynamic ranges, and
      numbers of discriminable steps. RESULTS: Speech processed via vocoder simulations
      representing focused stimulation was found to be substantially more intelligible
      than speech processed via a monopolar electric vocoder simulation, with
      differences of up to 60 percentage points. There were no significant differences,
      however, seen between the two focused approaches (signal attenuations of 10 and
      17 dB/mm) for the conditions investigated. Speech processed via the highly
      focused vocoder (17 dB/mm) was robust to constraints on small envelope dynamic
      range and small number of discriminable steps within the dynamic range, as high
      performance was maintained with at least a 5 dB dynamic range and eight or more
      discriminable steps. Significant drops in intelligibility were noted when the
      number of steps fell below eight. CONCLUSIONS: Highly focused stimulation
      tripolar electrical and infrared neural stimulation-has potential for increased
      performance in noise compared with monopolar stimulation, but much work remains
      to bear this potential out and to take full advantage of each modality's
      strengths.

PMID- 24322979
TI  - Increased risk of revision with hamstring tendon grafts compared with patellar
      tendon grafts after anterior cruciate ligament reconstruction: a study of 12,643
      patients from the Norwegian Cruciate Ligament Registry, 2004-2012.
AB  - BACKGROUND: The graft choice for anterior cruciate ligament reconstruction (ACLR)
      is controversial. Hamstring tendon (HT) autografts and patellar tendon (PT)
      autografts are the most common grafts used and have shown similar subjective and
      objective outcomes. PURPOSE: To compare the revision rate between HT and PT
      autografts used in ACLR in Norway and to estimate the influence of patient age
      and sex. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The study
      included all patients who underwent primary ACLR without concomitant ligament
      injuries registered in the Norwegian Knee Ligament Registry from 2004 through
      2012. The cohort was stratified by age group (15-19, 20-29, and >=30 years) and
      autograft type (HT or PT). Revision rates at 1, 2, and 5 years were calculated
      using the Kaplan-Meier analysis, and hazard ratios (HRs) for revision were
      calculated using multivariate Cox regression models. RESULTS: With a mean follow
      up of 4.0 years, 12,643 primary ACLRs were identified, with 3428 PT and 9215 HT
      grafts, among which 69 revisions with PT grafts and 362 revisions with HT grafts
      were performed. The overall 5-year revision rate was 4.2%. A higher revision rate
      was recorded for HT versus PT grafts at all follow-up times. When adjusted for
      sex, age, and type of graft, the HR for revision was 2.3 (95% CI, 1.8-3.0) for HT
      grafts compared with PT grafts. The HR for revision in the youngest age group was
      4.0 (95% CI, 3.1-5.2) compared with the oldest age group. Sex had no effect on
      the revision rate. CONCLUSION: Patients with HT grafts had twice the risk of
      revision compared with patients with PT grafts. Younger age was the most
      important risk factor for revision, and no effect was seen for sex. Further
      studies should be conducted to identify the cause of the increased revision rate
      found for HT grafts.

PMID- 24322980
TI  - Metastatic growth progression caused by PSGL-1-mediated recruitment of monocytes
      to metastatic sites.
AB  - Tumor cell-derived selectin ligands mediate contact to the endothelium,
      platelets, and leukocytes through binding to selectins that facilitates
      metastasis. Here, we describe the mechanism of how endogenous (non-tumor derived)
      selectin ligands contribute to metastasis using alpha(1,3)fucosyltransferase 7
      (Fuc-TVII(-/-))-deficient mice. Experimental metastasis of MC-38GFP and Lewis
      lung (3LL) carcinoma cells was attenuated in Fuc-TVII(-/-) mice, which express
      minimal amount of selectin ligands. We show that metastasis is dependent on
      selectin ligands carried on hematopoietic cells. P-selectin glycoprotein ligand-1
      (PSGL-1) was identified as the major ligand facilitating monocyte accumulation at
      metastatic sites. Reduced recruitment of monocytes to metastasizing tumor cells
      in Fuc-TVII(-/-) mice correlated with attenuated metastasis. Adoptive transfer of
      Fuc-T7(+) monocytes rescued metastasis in Fuc-TVII(-/-) mice, indicating that
      selectin ligand-dependent recruitment of monocytes is required for cancer
      progression. Cytokine analysis in metastatic lungs revealed high expression of
      CCL2 in C57BL/6 mice that was significantly lower in Fuc-TVII(-/-) mice. The
      absence of monocyte recruitment in Fuc-TVII(-/-) mice correlated with increased
      apoptosis of tumor cells. Thus, the recruitment of monocytes to metastasizing
      tumor cells is facilitated by endogenous selectin ligands on monocytes that
      enable efficient tumor cell survival, extravasation, and metastasis.

PMID- 24322981
TI  - Immune chaperone gp96 drives the contributions of macrophages to inflammatory
      colon tumorigenesis.
AB  - Macrophages are important drivers in the development of inflammation-associated
      colon cancers, but the mechanistic underpinnings for their contributions are not
      fully understood. Furthermore, Toll-like receptors have been implicated in colon
      cancer, but their relevant cellular sites of action are obscure. In this study,
      we show that the endoplasmic reticulum chaperone gp96 is essential in tumor
      associated macrophages (TAM) to license their contributions to inflammatory colon
      tumorigenesis. Mice where gp96 was genetically deleted in a macrophage-specific
      manner exhibited reduced colitis and inflammation-associated colon tumorigenesis.
      Attenuation of colon cancer in these mice correlated strikingly with reduced
      mutation rates of beta-catenin, increased efficiency of the DNA repair machinery,
      and reduced expression of proinflammatory cytokines, including interleukin (IL)
      17 and IL-23 in the tumor microenvironment. The genotoxic nature of TAM
      associated inflammation was evident by increased expression of genes in the DNA
      repair pathway. Our work deepens understanding of how TAM promote oncogenesis by
      altering the molecular oncogenic program within epithelial cells, and it
      identifies gp96 as a lynchpin chaperone needed in TAM to license their function
      and impact on expression of critical inflammatory cytokines in colon
      tumorigenesis.

PMID- 24322982
TI  - Cancer-derived mutations in KEAP1 impair NRF2 degradation but not ubiquitination.
AB  - NRF2 is a transcription factor that mediates stress responses. Oncogenic
      mutations in NRF2 localize to one of its two binding interfaces with KEAP1, an E3
      ubiquitin ligase that promotes proteasome-dependent degradation of NRF2. Somatic
      mutations in KEAP1 occur commonly in human cancer, where KEAP1 may function as a
      tumor suppressor. These mutations distribute throughout the KEAP1 protein but
      little is known about their functional impact. In this study, we characterized 18
      KEAP1 mutations defined in a lung squamous cell carcinoma tumor set. Four
      mutations behaved as wild-type KEAP1, thus are likely passenger events. R554Q,
      W544C, N469fs, P318fs, and G333C mutations attenuated binding and suppression of
      NRF2 activity. The remaining mutations exhibited hypomorphic suppression of NRF2,
      binding both NRF2 and CUL3. Proteomic analysis revealed that the R320Q, R470C,
      G423V, D422N, G186R, S243C, and V155F mutations augmented the binding of KEAP1
      and NRF2. Intriguingly, these "super-binder" mutants exhibited reduced
      degradation of NRF2. Cell-based and in vitro biochemical analyses demonstrated
      that despite its inability to suppress NRF2 activity, the R320Q "superbinder"
      mutant maintained the ability to ubiquitinate NRF2. These data strengthen the
      genetic interactions between KEAP1 and NRF2 in cancer and provide new insight
      into KEAP1 mechanics.

PMID- 24322984
TI  - A macrophage-specific fluorescent probe for intraoperative lymph node staging.
AB  - Successful identification of nodal metastases in patients with cancer is crucial
      to prescribe suitable treatment regimens that can improve recurrence-free
      survival. Although some new imaging technologies for nodal staging have been
      developed, such as nanoparticle-enhanced MRI and quantum-dot-based fluorescence
      imaging, sound technologies for intraoperative differentiation of metastatic and
      inflamed lymph nodes remain lacking. In this study, we illustrate the feasibility
      of using a macrophage-specific fluorescent probe (MFP) to visualize sentinel
      lymph nodes during surgery, highlighting abnormalities related to inflammation
      and tumor infiltration with signal enhancement and reduction methods using this
      technology. MFP was identified by high-throughput screening of fluorescent small
      molecule libraries synthesized with a diversity-oriented approach. It selectively
      visualized monocyte and macrophage cell populations in vitro, by live-cell
      imaging and flow cytometry, as well as in vivo, for imaging-guided surgery.
      Collectively, this study provides preclinical proof of concept for an
      intraoperative imaging platform to accurately assess lymph node status,
      eliminating the need for invasive nodal dissections that can contribute to
      complications of cancer therapy.

PMID- 24322985
TI  - Mechanical and electronic properties of pristine and Ni-doped Si, Ge, and Sn
      sheets.
AB  - Silicene, a graphene analogue of silicon, has been generating immense interest
      due to its potential for applications in miniaturized devices. Unlike planar
      graphene, silicene prefers a buckled structure. Here we explore the possibility
      of stabilizing the planar form of silicene by Ni doping using first principles
      density functional theory based calculations. It is found that planar as well as
      buckled structure is stable for Ni-doped silicene, but the buckled sheet has
      slightly lower total energy. The planar silicene sheet has unstable phonon modes.
      A comparative study of the mechanical properties reveals that the in-plane
      stiffness of both the pristine and the doped planar silicene is higher compared
      to that of the buckled silicene. This suggests that planar silicene is
      mechanically more robust. Electronic structure calculations of the planar and
      buckled Ni-doped silicene show that the energy bands at the Dirac point transform
      from linear behavior to parabolic dispersion. Furthermore, we extend our study to
      Ge and Sn sheets that are also stable and the trends of comparable mechanical
      stability of the planar and buckled phases remain the same. 

PMID- 24322983
TI  - A genetic mouse model of invasive endometrial cancer driven by concurrent loss of
      Pten and Lkb1 Is highly responsive to mTOR inhibition.
AB  - Signals from the tumor suppressors PTEN and LKB1 converge on mTOR to negatively
      regulate its function in cancer cells. Notably, both of these suppressors are
      attenuated in a significant fraction of human endometrial tumors. In this study,
      we generated a genetic mouse model of endometrial cancer driven by concomitant
      loss of these suppressors to gain pathophysiological insight into this disease.
      Dual loss of Pten and Lkb1 in the endometrial epithelium led to rapid development
      of advanced endometrioid endometrial tumors with 100% penetrance and short host
      survival. The tumors displayed dysregulated phosphatidylinositol 3-kinase
      (PI3K)/Akt and Lkb1/Ampk signaling with hyperactivation of mTOR signaling.
      Treatment with a dual PI3K/mTOR inhibitor, BEZ235, extended the time before tumor
      onset and prolonged overall survival. The PI3K inhibitor GDC-0941 used as a
      single agent reduced the growth rate of primary tumor implants in Pten/Lkb1
      deficient mice, and the mTOR inhibitor RAD001 was unexpectedly as effective as
      BEZ235 in triggering tumor regression. In parallel, we also found that ectopic
      expression of LKB1 in PTEN/LKB1-deficient human endometrial cancer cells
      increased their sensitivity to PI3K inhibition. Together, our results
      demonstrated that Pten/Lkb1-deficient endometrial tumors rely strongly on
      deregulated mTOR signaling, and they provided evidence that LKB1 status may
      modulate the response of PTEN-deficient tumors to PI3K or mTOR inhibitors.

PMID- 24322986
TI  - Implementing unique device identification in electronic health record systems:
      organizational, workflow, and technological challenges.
AB  - BACKGROUND: The United States Food and Drug Administration (FDA) has proposed
      creating a unique device identification (UDI) system for medical devices to
      facilitate postmarket surveillance, quality improvement, and other applications.
      Although a small number of health care institutions have implemented initiatives
      comparable with the proposed UDI system by capturing data in electronic health
      record (EHR) systems, it is unknown whether institutions with fewer resources
      will be able to similarly implement UDI. OBJECTIVE AND METHODS: This paper calls
      attention to organizational, workflow, and technological challenges in UDI system
      implementation by drawing from the literature on EHR and clinical research
      systems implementation. FINDINGS: Organizational challenges for UDI system
      implementation include coordinating multiple stakeholders to define UDI
      attributes and characteristics for use in EHRs, guiding organizational change
      within individual institutions for integrating UDI with EHRs, and guiding
      organizational change for reusing UDI data captured in EHRs. Workflow challenges
      include capturing UDI data in EHRs using keyboard entry and barcode scanning.
      Technological challenges involve interfacing UDI data between EHRs and surgical
      information systems, transforming UDI and related patient data from EHRs for
      research, and applying data standards to UDI within and beyond EHRs. DISCUSSION
      AND CONCLUSIONS: We provide recommendations for regulations, organizational
      sharing, and professional society engagement to raise awareness of and overcome
      UDI system implementation challenges. Implementation of the UDI system will
      require integration of people, process, and technology to achieve benefits
      envisioned by FDA, including improved postmarket device surveillance and quality
      of care.

PMID- 24322987
TI  - Diagnosis date agreement between SEER and Medicare claims data: impact on
      treatment.
AB  - BACKGROUND: A prior assessment of concordance between the diagnosis month in SEER
      records and Medicare claims found reasonable agreement; however, no assessment of
      the impact of discordance on cancer treatment ascertainment was conducted.
      OBJECTIVES: The aim of this study was to assess the concordance between the SEER
      diagnosis date (Sdx) and Medicare claim-derived diagnosis date and the impact of
      discordance on identification of treatment received. METHODS: The first Medicare
      claim date with a cancer diagnosis (Mdx) was compared with the Sdx among patients
      diagnosed with breast, colorectal, or lung cancer. The Mdx was considered
      concordant with the Sdx if the Mdx was within 16 days. Claims within 4 months
      after both the Mdx and Sdx were examined to collect treatment information.
      Treatment rate agreement was measured by kappa-statistics. RESULTS: Among 50,731
      breast, 51,025 colorectal, and 61,384 lung cancer patients, the Sdx and Mdx were
      concordant in 79%, 86%, and 73% of cases, respectively. Most discordant Mdx cases
      were identified in the month after the SEER diagnosis month. A small proportion
      of cases (7%-12%) preceded the SEER diagnosis month. Agreement for receipt of
      surgery was very good across all 3 cancer sites (kappa>0.88) and was excellent
      for radiation therapy (kappa>0.96). CONCLUSIONS: Although most cases were
      concordant for both diagnosis date and treatment ascertainment, there was still a
      small proportion of cases discordant for both diagnosis date and treatment
      identification. This study underscores the importance of examining claims in the
      months preceding diagnosis in the SEER-Medicare dataset to ensure patients are
      appropriately selected for analysis.

PMID- 24322988
TI  - Hospital teaching intensity and mortality for acute myocardial infarction, heart
      failure, and pneumonia.
AB  - BACKGROUND: Under the Affordable Care Act, health care reimbursement will
      increasingly be linked to quality and costs. In this environment, teaching
      hospitals will be closely scrutinized, as their care is often more expensive.
      Furthermore, although they serve vital roles in education, research, management
      of complex diseases, and care of vulnerable populations, debate continues as to
      whether teaching hospitals deliver better outcomes for common conditions.
      OBJECTIVE: To determine the association between risk-standardized mortality and
      teaching intensity for 3 common conditions. RESEARCH DESIGN: Using CMS models, 30
      day risk-standardized mortality rates were compared among US hospitals classified
      as Council of Teaching Hospital (COTH) members, non-COTH teaching hospitals, or
      nonteaching hospitals. These analyses were repeated using ratios of interns and
      residents to beds to classify teaching intensity. SUBJECTS: The study cohort
      included Medicare fee-for-service beneficiaries aged 66 years or older
      hospitalized in acute care hospitals during 2009-2010 for acute myocardial
      infarction (N = 342,145), heart failure (N = 647,081), or pneumonia (N =
      598,366). OUTCOME MEASURE: The 30-day risk-standardized mortality rates for each
      condition, stratified by teaching intensity. RESULTS: For each diagnosis,
      compared with nonteaching hospitals there was a 10% relative reduction in the
      adjusted odds of mortality for patients admitted to COTH hospitals and a 6%-7%
      relative reduction for patients admitted to non-COTH teaching hospitals. These
      findings were insensitive to the method of classifying teaching intensity and
      only partially explained by higher teaching hospital volumes. CONCLUSIONS: Health
      care reimbursement strategies designed to increase value should consider not only
      the costs but also the superior clinical outcomes at teaching hospitals for
      certain common conditions.

PMID- 24322989
TI  - Satisfaction with health care providers and preventive care adherence: a national
      study.
AB  - BACKGROUND: Prior studies demonstrating associations between patient satisfaction
      with health care providers and preventive adherence were cross-sectional,
      limiting causal inferences. In cross-sectional and prospective analyses, we
      explored 3 hypotheses previously invoked to explain associations between
      satisfaction with providers and preventive adherence: (1) receiving preventive
      care increases satisfaction; (2) enhancing satisfaction increases preventive
      care; (3) satisfaction and adherence reflect patient characteristics,
      incompletely adjusted for in previous studies. METHODS: We conducted 3 sets of
      logistic regression analyses employing 2000-2010 Medical Expenditure Panel Survey
      data: 1 cross-sectional and 2 prospective (baseline preventive care/follow-up
      year satisfaction, and baseline satisfaction/follow-up year preventive care),
      each set cumulatively adjusting for patient demographics, socioeconomics,
      morbidity, health care access, and medical skepticism. Consumer Assessment of
      Health Plans Survey items measured satisfaction with care from all providers in
      the preceding year. Preventive care examined included influenza vaccination and
      colorectal cancer, Papanicolaou, mammography, and prostate-specific antigen
      screening. RESULTS: In cross-sectional analyses adjusted for demographics (N =
      74,792), highest (vs. lowest) quartile satisfaction was associated with
      preventive adherence [adjusted odds ratios (95% confidence interval)]: influenza
      vaccination 1.14 (1.07, 1.22); colorectal cancer screening 1.08 (0.99, 1.18);
      Papanicolaou screening 1.14 (1.04, 1.24); mammography screening 1.20 (1.11,
      1.31); prostate-specific antigen screening 1.38 (1.25, 1.52). With full
      adjustment, associations of satisfaction with adherence were substantially
      attenuated, eliminated, or reversed. Prospective analyses yielded findings
      similar to the cross-sectional analyses. CONCLUSIONS: Cross-sectional and
      prospective associations between satisfaction with providers and preventive care
      adherence were similarly explained by patient characteristics. The findings
      question previously hypothesized causal relationships between satisfaction and
      preventive adherence.

PMID- 24322990
TI  - Impact of a high-deductible health plan on outpatient visits and associated
      diagnostic tests.
AB  - BACKGROUND: By shifting a greater share of out-of-pocket medical costs to
      consumers, high-deductible health plans (HDHP) might discourage use of essential
      outpatient services. OBJECTIVE: The objective of the study was to examine the
      impact of an HDHP on outpatient visits and associated laboratory and radiology
      tests. RESEARCH DESIGN/SUBJECTS: We used a pre-post with comparison group study
      design to examine the differential change in outpatient service utilization among
      7953 adults who were switched from a traditional Health Maintenance Organization
      plan to an HDHP compared with 7953 adults remaining in traditional plans. HDHP
      members had full coverage of preventive laboratory tests and modest copayments
      for outpatient visits, similar to controls, but faced full cost sharing under the
      deductible for radiology tests and laboratory tests not classified as preventive.
      RESULTS: Compared with controls, the HDHP group experienced moderate relative
      decreases in overall office visits (incidence rate ratios = 0.91, or a 9%
      relative reduction; 95% confidence interval: 0.88, 0.94) and visits for higher
      priority (0.91; 0.85, 0.97) and lower-priority (0.89; 0.81, 0.99) chronic
      conditions. There were no significant differences in changes in visit rates for
      acute higher-priority or lower-priority conditions (both 0.93; 0.86, 1.01) or
      preventive laboratory tests (0.97; 0.93, 1.02). HDHP members showed moderate
      relative reductions in the use of general laboratory tests (0.91; 0.86, 0.97) but
      not radiology tests (0.97; 0.91, 1.03). CONCLUSIONS: Chronic outpatient visits
      declined among HDHP members, although preventive laboratory tests and acute
      visits remained unchanged. HDHP patients with chronic illnesses who have more
      contact with the health care system might be more likely to reduce utilization
      because of increased exposure to costs associated with ambulatory visits.

PMID- 24322991
TI  - Risk factors and pathogens involved in early ventilator-acquired pneumonia in
      patients with severe subarachnoid hemorrhage.
AB  - Ventilator-acquired pneumonia (VAP) is a common burden in intensive care unit
      (ICU) patients, but, to date, specific data are not available in patients with
      severe aneurysmal subarachnoid hemorrhage (SAH). A single neuro-ICU retrospective
      analysis of 193 patients with SAH requiring mechanical ventilation (MV) >=48 h
      admitted from January 2005 to May 2010 was undertaken. The diagnosis of early VAP
      was prospectively upheld during a multidisciplinary staff meeting, according to
      the American Thoracic Society (ATS) 2005 guidelines with a threshold of 7 days
      after the onset of MV. Patients had a median age of 53 (44-62) years and 70 (36
      %) were male. The median Glasgow coma scale (GCS) score before MV was 9 (5-14).
      142 (74 %) patients had a World Federation of Neurosurgeons (WFNS) score >=III.
      Aneurysm was secured with an endovascular coiling procedure in 162 (84 %)
      patients. 81 (48.7 %) patients declared an early VAP. On multivariate analysis,
      male sex (odds ratio [OR] 2.26, 95 % confidence interval [CI] [1.14-4.46]), use
      of mannitol before day 7 (OR 3.03, 95 % CI [1.54-5.95]), and achieving enteral
      nutrition >=20 kcal kg(-1) day(-1) after day 7 (OR 2.91, 95 % CI [1.27-6.67])
      remained independent risk factors of VAP. The main pathogens involved were
      methicillin-susceptible Staphylococcus aureus (MSSA) (34.9 %), Haemophilus
      influenzae (28.1 %), Streptococcus pneumoniae (15.5 %), and Enterobacteriaceae
      (10.7 %). Early VAP was associated with a longer duration of MV and ICU stay, but
      not with an excess of mortality. Early VAP bears significant morbidity in
      patients with severe SAH. Pathogens involved in early VAP are susceptible to
      antibiotics. Among modifiable risk factors of VAP, early enteral nutrition could
      be an easy and effective target.

PMID- 24322993
TI  - Concurrent hyperfractionated accelerated radiotherapy with 5-FU and once weekly
      cisplatin in locally advanced head and neck cancer. The 10-year results of a
      prospective phase II trial.
AB  - PURPOSE: In this study, the acute toxicity and long-term outcome of a
      hyperfractionated accelerated chemoradiation regimen with cisplatin/5
      fluorouracil (5-FU) in patients with locally advanced squamous cell carcinomas of
      head and neck were evaluated. PATIENTS AND METHODS: From 2000-2002, 38 patients
      with stage III (5.3 %) and stage IV (94.7 %) head and neck cancer were enrolled
      in a phase II study. Patients received hyperfractionated-accelerated radiotherapy
      with 72 Gy in 15 fractions of 2 Gy followed by 1.4 Gy twice daily with
      concurrent, continuous infusion 5-FU of 600 mg/m(2) on days 1-5 and 6 cycles of
      weekly cisplatin (30 mg/m(2)). Acute toxicities (CTCAEv2.0), locoregional control
      (LRC), metastases-free (MFS), and overall survival (OS) were analyzed and
      exploratively compared with the ARO 95-06 trial. RESULTS: Median follow-up was
      11.4 years (95 % CI 8.6-14.2) and mean dose 71.6 Gy. Of the patients, 82 % had 6
      (n = 15) or 5 (n = 16) cycles of cisplatin, 5 and 2 patients received 4 and 3
      cycles, respectively. Grade 3 anemia, leukopenia, and thrombocytopenia were
      observed in 15.8, 15.8, and 2.6 %, respectively. Grade 3 mucositis in 50 %, grade
      3 and 4 dysphagia in 55 and 13 %. The 2-, 5-, and 10-year LRC was 65, 53.6, and
      48.2 %, the MFS was 77.5, 66.7, and 57.2 % and the OS 59.6, 29.2, and 15 %,
      respectively. CONCLUSION: Chemoradiation with 5-FU and cisplatin seems feasible
      and superior in terms of LRC and OS to the ARO 95-06C-HART arm at 2 years.
      However, this did not persist at the 5- and 10-year follow-ups.

PMID- 24322994
TI  - A pilot study on potential plasma hypoxia markers in the radiotherapy of non
      small cell lung cancer. Osteopontin, carbonic anhydrase IX and vascular
      endothelial growth factor.
AB  - BACKGROUND: Hypoxic radioresistance plays a critical role in the radiotherapy of
      cancer and adversely impacts prognosis and treatment response. This prospective
      study investigated the interrelationship and the prognostic significance of
      several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients
      treated by radiotherapy +/- chemotherapy. MATERIAL AND METHODS: Pretreatment
      osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic
      anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0)
      patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker
      correlation, association with clinicopathological parameters and the prognostic
      value of a biomarker combination was evaluated. RESULTS: All biomarkers were
      linearly correlated and linked to different clinical parameters including lung
      function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High
      OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly
      associated with poor survival. Double marker combination additively increased the
      risk of death by a factor of 2 and high plasma levels of the triple combination
      OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined
      assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03)
      in a multivariate Cox regression model including N stage, T stage and GTV.
      CONCLUSION: This pilot study suggests that a co-detection augments the prognostic
      value of single markers and that the integration of OPN, VEGF and CA IX into a
      hypoxic biomarker profile for the identification of patients with largely hypoxic
      and radioresistant tumors should be further evaluated.

PMID- 24322995
TI  - Quality of patient positioning during cerebral tomotherapy irradiation using
      different mask systems.
AB  - BACKGROUND AND PURPOSE: Patient immobilization during brain tumor radiotherapy is
      achieved by employing different mask systems. Two innovative mask systems were
      developed to minimize the problems of claustrophobic patients. Our aim was to
      evaluate whether the quality of patient immobilization using the new mask systems
      was equivalent to the standard mask system currently in use. MATERIAL AND
      METHODS: Thirty-three patients with cerebral target volumes were irradiated using
      the Hi-Art II tomotherapy system between 2010 and 2012. Each group of 11 patients
      was fitted with one of the two new mask systems (Crystal(r) or Open Face(r) mask,
      Orfit) or the standard three-point mask (Raycast(r)-HP, Orfit) and a total of 557
      radiotherapy fractions were evaluated. After positioning was checked by MV-CT,
      the necessary table adjustments were noted. Data were analyzed by comparing the
      groups, and safety margins were calculated for nonimage-guided irradiation.
      RESULTS: The mean values of the table adjustments were: (a) lateral (mm): - 0.22
      (mask 1, standard deviation (sigma): 2.15); 1.1 (mask 2, sigma: 2.4); - 0.64
      (mask 3, sigma: 2.9); (b) longitudinal (mm): - 1 (mask 1, sigma: 2.57); - 0.5
      (mask 2, sigma: 4.7); - 1.22 (mask 3, sigma: 2.52); (c) vertical (mm): 0.62 (mask
      1, sigma: 0.63); 1.2 (mask 2, sigma: 1.0); 0.57 (mask 3, sigma: 0.28); (d) roll:
      0.35 degrees  (mask 1, sigma: 0.75); 0 degrees  (mask 2, sigma: 0.8); 0.02
      degrees  (mask 3, sigma: 1.12). The outcomes suggest necessary safety margins of
      5.49-7.38 mm (lateral), 5.4-6.56 mm (longitudinal), 0.82-3.9 mm (vertical), and
      1.93-4.5 degrees  (roll). There were no significant differences between the
      groups. CONCLUSIONS: The new mask systems improve patient comfort while providing
      consistent patient positioning.

PMID- 24322996
TI  - A retrospective review of acupuncture use for the treatment of pain in sickle
      cell disease patients: descriptive analysis from a single institution.
AB  - OBJECTIVES: This retrospective study describes the use of acupuncture for adult
      sickle cell patients in a single institution. MATERIALS AND METHODS: We
      identified 47 sickle cell disease patients referred for acupuncture at the
      National Institutes of Health between January 2005 and September 2011. All
      patients were enrolled in a Study of the Natural History of sickle cell disease
      and signed consent. We reviewed patient demographics, location of acupuncture
      treatment sessions (inpatient vs. outpatient), number of sessions received, sites
      of pain, patient pain reporting, and the use of other complementary therapies.
      RESULTS: Of the 47 patients (60% women, median age 36 y) referred for
      acupuncture, 42 had homozygous SS disease (89%) and 5 had SC disease (11%). Over
      half of the patients (51%) reported >3 sites of pain. Only 24 patients (51%)
      underwent acupuncture treatment. Of those who elected not to receive acupuncture,
      a majority (87%) accepted some other forms of complementary therapies. Nine
      patients underwent only inpatient acupuncture for acute vaso-occlusive crisis.
      Eleven patients received only outpatient acupuncture treatment for chronic pain,
      and 4 patients received both inpatient and outpatient treatments. For the
      patients who received inpatient acupuncture treatment for acute vaso-occlusive
      crisis, there was a significant reduction of reported pain score immediately
      after acupuncture treatment with an average pain reduction of 2.1 points on the
      numeric pain scale (P<0.0001). Excluding the 2 outliers, 75% of patients (n=13)
      in the outpatient setting described their pain as improved compared with prior
      session. DISCUSSION: To our knowledge, this is the largest retrospective review
      of acupuncture use in the sickle cell population. This analysis describes the use
      of acupuncture and raises the possibility of its use as an adjuvant for pain
      management in this population. Future clinical trials are needed to evaluate
      acupuncture's efficacy and effectiveness for pain management in different
      treatment settings and for various types of pain etiologies among the sickle cell
      population.

PMID- 24322998
TI  - Engineering entanglement: controlling the formation of polycatenanes and
      polyrotaxanes using pi interactions.
AB  - A reproducible metallocyclic motif containing amino-acid functionalised aromatic
      diimides has been employed to demonstrate remarkable control over entanglement
      topologies. [2]-Catenane and pseudo-rotaxane units give rise to 1D -> 2D
      polycatenation, the formation of which can be sterically prevented, and a unique
      1D -> 3D polyrotaxane. 

PMID- 24322999
TI  - Food memory: neuronal involvement in food recognition.
AB  - Previous studies indicate that ablation of the temporal cortex including the
      amygdala (AM) and hippocampal formation (HF) induce the Kluver-Bucy syndrome in
      which animals cannot discriminate food from nonfood. Of 710 AM neurons tested,
      129 (18.2%) responded to single sensory stimulation (48 to vision, 32 to
      audition, 49 to ingestion), 142 (20.0%) to multimodal stimulation and 20 to only
      one item with affective significance. Eight food related AM neurons were tested
      in reversal by salting food or introducing saline, and all responses were
      modulated by reversal. In HF and parahippocampal cortices (PH), 864 neurons were
      recorded, and 160 (18.5%) responded lo the sight of certain objects. Of these, 23
      responded predominantly to food related rewarding objects, 13 to several aversive
      objects such as a spider model, syringe, objects associated with weak electric
      shock, ten to one object or one kind of object, seven to unfamiliar objects. Of
      14 rewarding or aversive object-related neurons tested, responses of seven to the
      same test object did not change in extinction or reversal tests. Although
      responses of the other seven decreased in extinction or reversal tests, the
      magnitude of response remaining in five of those seven still exceeded that of
      responses to other categories. Results suggest complementary AM and HF-PH
      functions. The AM may be important in ongoing recognition of the affective
      significance of complex stimuli (food-nonfood discrimination) and the HF-PH in
      sustaining past affective significance. 

PMID- 24323000
TI  - Protein energy malnutrition, thyroid hormones and goitre among Malaysian
      Aborigines and Malays.
AB  - The relationship between malnutrition, goitre and thyroid hormones was studied
      among Aborigines and Malays in Ulu Langat, Malaysia. Fifty Aborigines aged
      >=7years were selected randomly for anthropometric, clinical and hormonal
      assessment. Fifty Malays of similar age from the nearby Malay village were chosen
      as controls. The Aborigines had a higher prevalence of malnutrition and goitre
      compared to the Malays. The prevalence of goitre was 26.5% amongst Aborigines and
      19.6% among the Malays. All the nutritional indexes measured were significantly
      different between the two communities, especially among females. The differences
      corresponded to significant differences in levels of thyroid-stimulating hormone
      (TSH) measured using a highly sensitive TSH assay. By univariate analysis the
      increase in TSH corresponded to the decrease in body mass index (BMI). On the
      other hand, no association was found between BMI and goitres. No thyroid
      autoantibodies were detected and all subjects were clinically euthyroid and had
      normal thyroxine and triidothyronine levels. However, consumption of cassava
      conferred a four-fold risk of developing goitres. The high prevalence of goitres
      in malnourished subjects in this region which is not known to be iodine deficient
      could be due to cassava consumption. 

PMID- 24322997
TI  - Diffusion tensor tractography and neuropsychological assessment in patients with
      vitamin B12 deficiency.
AB  - INTRODUCTION: Structural imaging of the brain does not demonstrate any changes in
      a vast majority of patients with vitamin B12 deficiency, even in advanced stages.
      In this study, we aimed to assess and correlate the functional integrity of the
      brain fiber tracts using diffusion tensor tractography with neuropsychological
      examination in patients with vitamin B12 deficiency. METHODS: The study was
      conducted at two tertiary care centers. Thirty-two patients with vitamin B12
      deficiency were enrolled and subjected to diffusion tensor tractography, as an
      extension of diffusion tensor imaging, and neuropsychological assessment. Tests
      of significance were done to detect changes, pre- and post-vitamin B12
      supplementation in the diffusivity parameters (fractional anisotropy and mean
      diffusivity) and the neuropsychological test scores. RESULTS: Statistically
      significant changes were observed in the diffusivity parameters and the
      neuropsychological test scores between the controls and the patients with vitamin
      B12deficiency in the pre- and post-treatment phases. CONCLUSIONS: This is the
      first study to evaluate the diffusion tensor tractography (DTT) parameters in the
      light of clinical neuropsychological assessment in patients with vitamin B12
      deficiency. Utilization of DTT parameters may antedate structural changes and may
      quantify the neurocognitive deficits.

PMID- 24323001
TI  - Early life factors affecting body mass index and waist-hip ratio in adolescence.
AB  - A study of the relative contribution of early, parental, contemporary influences
      on body mass index (BMI) and waist-hip ratio (WHR) in adolescence was carried out
      in 213 families with adolescents in Geelong, Victoria, Australia. Weight, height
      and body circumferences were measured in both parents and children and other
      relevant information was obtained by questionnaire. The parents of the families
      studied were broadly representative of the Geelong workforce. The data obtained
      were divided into three categories: early life, parental and contemporary. The
      early life influences studied were sociodemographic environment, illness during
      the first year of life, infant feeding practices, weight, height and rate of
      growth. Parental factors included socioeconomic and anthropometric
      characteristics. Contemporary influences, studied in the adolescents, included
      sociodemographic, lifestyle and anthropometric data as for the parents.
      Multivariate analyses (multiple regression analysis) was used to determine the
      strongest influence on BMI from each of the following categories: early life,
      parental and contemporary. Subsequently the factors identified from each of these
      three categories were combined in a further multiple regression analysis to
      determine the strongest overall determinants for BMI and WHR in adolescence.
      Apart from gender, only BMI at 50 months contributed significantly to BMI in
      adolescence. Similarly, apart from gender, only BMI at 80 months was a
      significant determinant of WHR in adolescence. 

PMID- 24323002
TI  - Clinical nutrition in East Asia and the Pacific.
AB  - Identifying the nutrition problems of Asia and the Pacific is made difficult by
      the enormous geographic, socioeconomic and cultural diversity that exists in
      these areas. With increasing longevity and reduced infant mortality, the more
      chronic diseases are becoming increasingly important. For almost 90% of the
      countries that keep such data in the Western Pacific Region of WHO, at least
      three of the five leading causes of death are noncommunicable diseases.
      Nevertheless undernutrition is still the most important nutritional problem in
      the Region. Even though there have been some encouraging declines in the
      proportion of malnourished under 5-year-olds, increasing populations have meant
      the actual numbers have not declined. Vitamin A deficiency, iodine deficiency
      disorders and iron deficiency anaemia remain major public health problems in many
      countries. There is evidence that vitamin A deficiency is appearing in countries
      in which it has not previously been a problem. New challenges are occurring, such
      as childhood obesity, the susceptibility of undernourished populations to the
      human immunodeficiency virus and the increase in noncommunicable diseases. The
      three arms of clinical nutrition: therapeutic, research and public health will
      need to work closely to meet the considerable and continuing threat posed by the
      nutrition-related diseases. 

PMID- 24323003
TI  - Nutrition and gastrointestinal disorders.
AB  - The gastrointestinal tract, including the liver and pancreas, is a complex system
      whose function is to process a wide range of nutrient and other products enabling
      their absorption as well as detoxification and excretion. During the process,
      food is converted into energy and into other substances that are used by cells
      throughout the entire body. Many diseases can affect the various organs of the
      gastrointestinal (GI) system and diet plays a relatively minor role in the onset
      of such GI diseases. Recently it has become clear that glutamine, a 'non
      essential' amino acid, is important in the maintenance of intestinal mucosal
      metabolism, structure and function. Dietary fibre has complicated properties
      including trophic effects on intestinal mucosa, volatile fatty acid production,
      alteration of bacterial flora and faecal bacterial mass and change in faecal bile
      acids. Gastrointestinal disease many result from deficiency or excess of specific
      nutrients in normal individuals. In allergic or susceptible subjects, diseases
      such as food allergy, disaccharidase intolerance and gluten sensitive enteropathy
      may occur with intake of normal daily requirements. In genetically susceptible
      individuals, specific nutrients have been linked, based on epidemiological
      studies and animal experimentation, to carcinoma of the stomach (high starch,
      high nitrate foods and smoked meats) and colon (low fibre, high fat, low vitamin
      A). A recent Australian multi-centre polyp prevention project has recruited
      subjects with adenomatous polyps cleared at colonoscopy. Subjects were randomised
      to receive high fibre, low fat, b -carotene or a combination of these and
      compared to an unchanged control group at 2-yearly follow up colonoscopy. Low fat
      and high fibre were not protective against polyp development; however, b 
      carotene ingestion was associated with an increased risk. Duodenal ulcer disease
      is multifactorial with gastric acid and H. pylori induced gastroduodenitis
      playing important aetiological roles. Protection is afforded to individuals with
      a higher unsaturated fatty acid and lower refined sugar intakes. Treatment of
      gastrointestinal disease may require dietary modifications or, if the gut is not
      functioning adequately, nutritional support via the parenteral route. In subjects
      with inflammatory bowel disease and short gut syndrome replacement of specific
      nutrients may be required particularly calcium, magnesium, zinc, iron, and
      vitamins B12, folate, D and A. Controversy still exists as to the role of
      parenteral and enteral nutrition as primary therapy for inflammatory bowel
      disease. 

PMID- 24323004
TI  - Diet and cancer - some results from Singapore.
AB  - The notion that diet has an aetiological role in cancer is generally accepted,
      although the actual agents and mechanisms are still subjects of much research. A
      major problem in this work is the lack of effective instruments in determining
      dietary exposures. The wide margin given as the likely population attributable
      risk (10-70%) is an indication of the relative imprecision of our state of
      knowledge at this moment. In Singapore, digestive tract cancers account for about
      30% of all cancers in males and 24% in fem les. In addition, other cancers that
      have a strong dietary link include lung (24% males, 10% females), liver (9%
      males, 4% females), nasopharynx (7% males, 4% females), female breast (17%) and
      prostate (3%). Therefore, this is a very important subject for continued study in
      view of the preventive potential. Based on recent studies conducted in Singapore,
      a review is provided of factors associated with colorectal and breast cancers.
      The main thrust of our findings point to the rob of me t s ~ predisposing factor
      and vegetables/fruits as protective foods. Possible agents and mechanisms of
      action will be discussed. 

PMID- 24323005
TI  - The development of food and nutrition policy in Australia, with special attention
      to the State of Victoria.
AB  - Only 6% of Australia's workforce is engaged in agriculture but the country
      produces enough food for around 35 million people - more than half of them
      purchasers of exports. The federal political system includes 6 states and 2
      territories, with states having responsibility for many aspects of health and
      agricultural policy. During the 1950s and 1960s Australia experienced a marked
      rise in ischaemic heart disease and death rates in middle aged men rose. With the
      onset of the economic slowdown in the 1970s, governments also looked to
      preventive measures to contain health service costs. In 1979 the Commonwealth
      Department of Health adopted 8 non-quantitative dietary guidelines and in 1986 a
      national Better Health Commission recommended a coordinated program to change
      dietary habits. Developments in Victoria were stimulated by a conference on
      'Agriculture and human nutrition' in 1983. Following this a report 'Making
      healthy choices easy choices: towards a food and nutrition policy for Victoria'
      was released in November 1984 and the state government began a Food and Nutrition
      Project to stimulate intersectoral activity to promote lower risk eating
      patterns. In March 1987 the Victorian government formally adopted a food and
      nutrition policy and established an Interdepartmental Committee on Food and
      Nutrition with representation for Health, Agriculture and Rural Affairs,
      Education and Industry, Technology and Resources and a Food and Nutrition
      Community Consultative Group. Increasing financial stringency in the late 1980s
      was fortuitously offset by the availability of funds from the Victorian Health
      Promotional Foundation, funded by a 10% surtax on tobacco. 

PMID- 24323006
TI  - Statistics of the sparse spectrum turbulent phase.
AB  - A recently published sparse spectrum (SS) model of the phase front perturbations
      by atmospheric turbulence [J. Opt. Soc. Am. A 30, 479 (2013)] is based on the
      trigonometric series with discrete random support. The SS model enables fewer
      computational efforts, while preserving the wide range of scales typically
      associated with turbulence perturbations. We present an improved version of the
      SS model that accurately reproduces the power-law spectral density of the phase
      fluctuations in the arbitrary wide spectral band. We examine the higher-order
      statistics of the SS phase samples for four versions of the SS model. We also
      present the calculations of the long-exposure Strehl numbers and scintillation
      index for the different versions of the SS model. A nonoverlapping SS model with
      a log-uniform partition emerges as the most appropriate for the atmospheric
      turbulence representation.

PMID- 24323007
TI  - Elastomeric 2D grating and hemispherical optofluidic chamber for multifunctional
      fluidic sensing.
AB  - We present an optofluidic sensor based on an elastomeric two-dimensional (2D)
      grating integrated inside a hemispherical fluid chamber. A laser beam is
      diffracted before (reflection) and after (transmission) going through the grating
      and liquid in the dome chamber. The sensing mechanism is investigated and
      simulated with a finite-difference time-domain-based electromagnetic method. For
      the experiment, by analyzing the size, power, and shape of the 2D diffraction
      patterns, we can retrieve multiple parameters of the liquid, including the
      refractive index, pressure, and opacity with high sensitivity. We demonstrate
      that the glucose concentration can be monitored when mixed in a different
      concentrated phosphate-buffered saline solution. The free-solution binding of
      bovine serum albumin (BSA) and anti-BSA IgG is detected with this optical sensor.
      This low-cost, multifunctional, and reliable optofluidic sensor has the potential
      to be used as a monitor of biofluid, such as blood in hemodialysis. 

PMID- 24323008
TI  - Near-field imaging of perfectly conducting grating surfaces.
AB  - A novel approach is presented to solving the inverse diffractive grating problem
      in near-field optical imaging, which is to reconstruct perfectly conducting
      grating surfaces with resolution beyond the diffraction limit. The grating
      surface is assumed to be a small and smooth deformation of a plane surface. An
      analytical solution of the direct grating problems is derived by using the method
      of transformed field expansion. Based on the analytic solution, an explicit
      reconstruction formula is deduced for the inverse grating problem. The method
      requires only a single incident field and is realized efficiently by using the
      fast Fourier transform. Numerical results show that the method is simple, stable,
      and effective in reconstructing grating surfaces with super-resolved resolution. 

PMID- 24323009
TI  - Laser tomography adaptive optics: a performance study.
AB  - We present an analytical derivation of the on-axis performance of adaptive optics
      systems using a given number of guide stars of arbitrary altitude, distributed at
      arbitrary angular positions in the sky. The expressions of the residual error are
      given for cases of both continuous and discrete turbulent atmospheric profiles.
      Assuming Shack-Hartmann wavefront sensing with circular apertures, we demonstrate
      that the error is formally described by integrals of products of three Bessel
      functions. We compare the performance of adaptive optics correction when using
      natural, sodium, or Rayleigh laser guide stars. For small diameter class
      telescopes (?5 m), we show that a small number of Rayleigh beacons can provide
      similar performance to that of a single sodium laser, for a lower overall cost of
      the instrument. For bigger apertures, using Rayleigh stars may not be such a
      suitable alternative because of the too severe cone effect that drastically
      degrades the quality of the correction.

PMID- 24323010
TI  - Linear equations method for modal decomposition using intensity information.
AB  - The linear equations method is proposed to calculate the complete modal content
      of the partially coherent laser beam using only the intensity information. This
      method could give not only the incoherent expansion coefficients of the modal
      decomposition but also the cross-correlation expansion coefficients using the
      intensity profiles in several planes of finite distance along the propagation
      direction. A simulation is also presented to verify the validity of this theory.
      In our algorithm, the minimum and maximum mode orders should be known a priori,
      so we provide an estimation method for the two parameters. 

PMID- 24323011
TI  - Efficient integral equation-based analysis of finite periodic structures in the
      optical frequency range.
AB  - The optical response of dense finite arrays of nanoparticles can be efficiently
      analyzed with the help of macro basis functions obtained by employing the array
      scanning method. This is demonstrated by analyzing optical collimation in arrays
      of silver nanorods. The accuracy of the solution obtained with the proposed
      method has been validated by comparison with solutions obtained employing the
      Krylov subspace iterative method. The relative error in the electric field
      distribution on an observation plane above the finite array is of the order of 
      25 dB, while the number of unknowns is reduced by a factor of 32.

PMID- 24323012
TI  - Generalization of the optical theorem for light scattering from a particle at a
      planar interface.
AB  - The optical theorem provides a powerful tool for calculating the extinction cross
      section of a particle from a solution to Maxwell's equations, relating the cross
      section to the scattering amplitude in the forward direction. The theorem has
      been generalized by a number of other workers to consider a particle near an
      interface between media with different refractive indices. Here we present a
      derivation of the generalized optical theorem that is valid for a particle
      embedded in the interface, as well as an incident beam undergoing total internal
      reflection. We also obtain an additional useful physical result: we show that the
      far-field scattered field must be zero in the direction parallel to the
      interface. Our results enable the verification of computations of scattering by
      particles embedded in interfaces and may be relevant to experiments on colloidal
      particles at fluid interfaces. 

PMID- 24323013
TI  - Ray transfer matrix for a spiral phase plate.
AB  - We present a ray transfer matrix for a spiral phase plate. Using this matrix we
      determine the stability of an optical resonator made of two spiral phase plates
      and trace stable ray orbits in the resonator. Our results should be relevant to
      laser physics, optical micromanipulation, quantum information, and optomechanics.

PMID- 24323014
TI  - Computationally efficient finite-difference modal method for the solution of
      Maxwell's equations.
AB  - In this work, a new implementation of the finite-difference (FD) modal method
      (FDMM) based on an iterative approach to calculate the eigenvalues and
      corresponding eigenfunctions of the Helmholtz equation is presented. Two relevant
      enhancements that significantly increase the speed and accuracy of the method are
      introduced. First of all, the solution of the complete eigenvalue problem is
      avoided in favor of finding only the meaningful part of eigenmodes by using
      iterative methods. Second, a multigrid algorithm and Richardson extrapolation are
      implemented. Simultaneous use of these techniques leads to an enhancement in
      terms of accuracy, which allows a simple method such as the FDMM with a typical
      three-point difference scheme to be significantly competitive with an analytical
      modal method. 

PMID- 24323015
TI  - Analysis of the impacts of horizontal translation and scaling on wavefront
      approximation coefficients with rectangular pupils for Chebyshev and Legendre
      polynomials.
AB  - Chebyshev and Legendre polynomials are frequently used in rectangular pupils for
      wavefront approximation. Ideally, the dataset completely fits with the polynomial
      basis, which provides the full-pupil approximation coefficients and the
      corresponding geometric aberrations. However, if there are horizontal translation
      and scaling, the terms in the original polynomials will become the linear
      combinations of the coefficients of the other terms. This paper introduces
      analytical expressions for two typical situations after translation and scaling.
      With a small translation, first-order Taylor expansion could be used to simplify
      the computation. Several representative terms could be selected as inputs to
      compute the coefficient changes before and after translation and scaling. Results
      show that the outcomes of the analytical solutions and the approximated values
      under discrete sampling are consistent. With the computation of a group of
      randomly generated coefficients, we contrasted the changes under different
      translation and scaling conditions. The larger ratios correlate the larger
      deviation from the approximated values to the original ones. Finally, we analyzed
      the peak-to-valley (PV) and root mean square (RMS) deviations from the uses of
      the first-order approximation and the direct expansion under different
      translation values. The results show that when the translation is less than 4%,
      the most deviated 5th term in the first-order 1D-Legendre expansion has a PV
      deviation less than 7% and an RMS deviation less than 2%. The analytical
      expressions and the computed results under discrete sampling given in this paper
      for the multiple typical function basis during translation and scaling in the
      rectangular areas could be applied in wavefront approximation and analysis. 

PMID- 24323016
TI  - Propagation of electromagnetic beams of any state of spatial coherence and
      polarization through multilayered stratified media.
AB  - We present a theory of propagation of a partially coherent and partially
      polarized electromagnetic beam through a multilayered stratified medium. The
      analysis shows that spatial coherence and polarization properties of the beam
      change, in general, on propagation through such a medium. We illustrate the
      results by an example. 

PMID- 24323017
TI  - Array of polarization singularities in interference of three waves.
AB  - In this paper, we show that arrayed polarization singularities (PSs) can be
      generated by interference of three polarized waves. An experimental setup was
      proposed and used to produce one of the available types of array structures. We
      then analytically identified factors that control the structures of these arrays
      and classified all the structures into three types. Simulation results were used
      to assist this analysis. 

PMID- 24323018
TI  - Reflection of Laguerre-Gaussian beams carrying orbital angular momentum: a full
      Taylor expanded solution.
AB  - Partial reflection of linearly polarized Laguerre-Gaussian beams incident at a
      dielectric interface are studied beyond the paraxial regime. Based on the angular
      spectrum method and Taylor series expansion, we derive exact analytical
      expressions for the reflected electric field. This result holds in both the
      paraxial and nonparaxial regimes. The result is then extended to beams of
      arbitrary polarization and used to analytically calculate the transverse and
      longitudinal shifts of the beams' center of gravity. Finally, several numerical
      examples are performed to verify the analytical formulas we derived near the
      Brewster angle. 

PMID- 24323019
TI  - Quantitative surface radiance mapping using multiview images of light-emitting
      turbid media.
AB  - A novel method is presented for accurately reconstructing a spatially resolved
      map of diffuse light flux on a surface using images of the surface and a model of
      the imaging system. This is achieved by applying a model-based reconstruction
      algorithm with an existing forward model of light propagation through free space
      that accounts for the effects of perspective, focus, and imaging geometry. It is
      shown that flux can be mapped reliably and quantitatively accurately with very
      low error, <3% with modest signal-to-noise ratio. Simulation shows that the
      method is generalizable to the case in which mirrors are used in the system and
      therefore multiple views can be combined in reconstruction. Validation
      experiments show that physical diffuse phantom surface fluxes can also be
      reconstructed accurately with variability <3% for a range of object positions,
      variable states of focus, and different orientations. The method provides a new
      way of making quantitatively accurate noncontact measurements of the amount of
      light leaving a diffusive medium, such as a small animal containing fluorescent
      or bioluminescent markers, that is independent of the imaging system
      configuration and surface position. 

PMID- 24323020
TI  - Computational model of the effect of light scattering from cataracts in the human
      eye.
AB  - A model of the human eye has been developed, including scattering from cataracts
      inside the nucleus of the lens. The cataracts are modeled as spherical particles
      with refractive index different from that of the surrounding lens medium.
      Scattering from the retina is also included in the simulations. Variations of
      scattering particle diameter, number of particles, and wavelength of the
      illuminating light are investigated. It is shown that particle size is the most
      important parameter affecting the scattered light, and that the scattering from
      the retina can mask the effect of the scattering particles, for some range of the
      parameters. 

PMID- 24323021
TI  - Automated segmentation of retinal pigment epithelium cells in fluorescence
      adaptive optics images.
AB  - Adaptive optics (AO) imaging methods allow the histological characteristics of
      retinal cell mosaics, such as photoreceptors and retinal pigment epithelium (RPE)
      cells, to be studied in vivo. The high-resolution images obtained with ophthalmic
      AO imaging devices are rich with information that is difficult and/or tedious to
      quantify using manual methods. Thus, robust, automated analysis tools that can
      provide reproducible quantitative information about the cellular mosaics under
      examination are required. Automated algorithms have been developed to detect the
      position of individual photoreceptor cells; however, most of these methods are
      not well suited for characterizing the RPE mosaic. We have developed an algorithm
      for RPE cell segmentation and show its performance here on simulated and real
      fluorescence AO images of the RPE mosaic. Algorithm performance was compared to
      manual cell identification and yielded better than 91% correspondence. This
      method can be used to segment RPE cells for morphometric analysis of the RPE
      mosaic and speed the analysis of both healthy and diseased RPE mosaics. 

PMID- 24323022
TI  - Effects of dielectric planar interface on tight focusing coherent beam: direct
      comparison between observations and vectorial calculation of lateral focal
      patterns.
AB  - We report direct observation of lateral focal patterns through an acrylic
      material to investigate the effects of aberrations caused by a planar dielectric
      interface. Numerical analyses based on vectorial Huygens-Fresnel diffraction
      theory were also performed to examine the behavior of three-dimensional point
      spread functions. Experimental and numerical results showed agreement of the
      behavior of the peak position in the focal patterns with changes in the interface
      position. Our approach has the potential to predict the effects of aberrations in
      confocal laser scanning microscopes and super-resolution applications. 

PMID- 24323023
TI  - Elementary-field analysis of partially coherent beam shaping.
AB  - We consider spatial shaping of partially coherent fields in two types of optical
      systems: a 2F Fourier-transforming system with the beam shaping element in the
      input plane and a 4F imaging system with the element in the intermediate Fourier
      plane. Different representations of the spatially partially coherent field in
      terms of fully coherent fields are examined to permit reduction of the
      dimensionality of the propagation integrals. The standard Mercer-type coherent
      mode representation of the incident cross-spectral density (CSD) function is
      compared to expansions of CSD in either spatially or angularly shifted elementary
      field modes, all sharing the same spatial profile. In Fourier-transforming
      systems, the angular elementary-field representation proves computationally
      superior, while in imaging systems the spatially shifted elementary-field
      expansion is the best choice. Considering the Fourier-plane element as a
      generalized pupil, the latter leads to the concept's generalized amplitude
      associated with the elementary field and to a generalized transfer function of
      the system. These concepts reduce to the standard point spread function and the
      optical transfer function in the limit of spatial incoherence at the object
      plane. Examples of the effects of partial coherence in spatial beam shaping are
      given. 

PMID- 24323024
TI  - Angular control of optical cavities in a radiation-pressure-dominated regime: the
      Enhanced LIGO case.
AB  - We describe the angular sensing and control (ASC) of 4 km detectors of the Laser
      Interferometer Gravitational-Wave Observatory (LIGO). Enhanced LIGO, the
      culmination of the first generation LIGO detectors, operated between 2009 and
      2010 with about 40 kW of laser power in the arm cavities. In this regime,
      radiation-pressure effects are significant and induce instabilities in the
      angular opto-mechanical transfer functions. Here we present and motivate the ASC
      design in this extreme case and present the results of its implementation in
      Enhanced LIGO. Highlights of the ASC performance are successful control of opto
      mechanical torsional modes, relative mirror motions of <= 1*10(-7) rad rms, and
      limited impact on in-band strain sensitivity.

PMID- 24323025
TI  - Diffraction by nanocrystals.
AB  - X-ray femtosecond nanocrystallography is a new, potentially powerful technique
      for imaging biological macromolecules that uses ensemble-averaged measurements of
      diffraction of x-ray free-electron laser pulses from nanocrytalline specimens.
      Nanocrystals have some diffraction characteristics that are distinct from those
      of macroscopic crystals, due to the presence of different kinds of unit cell in
      the crystal and of truncated unit cells on the crystal surface. Expressions are
      derived for diffraction by nanocrystals with variable and incomplete unit cells,
      averaged over a distribution of crystal sizes and shapes. The diffraction
      contains differently modulated Bragg components that are due to interference
      effects within and between the full and incomplete unit cells. Estimates are
      obtained for the relative magnitudes of the components. The nature of the
      diffraction is illustrated by two-dimensional simulations. Implications for
      molecular imaging are discussed. 

PMID- 24323026
TI  - Phase I study of neratinib in combination with temsirolimus in patients with
      human epidermal growth factor receptor 2-dependent and other solid tumors.
AB  - PURPOSE: Human epidermal growth factor (HER) -mediated signaling is critical in
      many cancers, including subsets of breast and lung cancer. HER family members
      signal via the phosphatidylinositide 3-kinase (PI3K) -AKT/protein kinase B
      mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the
      expression of multiple contributors to tumor growth and invasion. On the basis of
      preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in
      breast and lung cancer models, we conducted a phase I combination study of
      neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and
      temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors. PATIENTS
      AND METHODS: This study enrolled patients to dosing combinations of neratinib and
      temsirolimus. The primary objective was to estimate the toxicity contour of the
      combination and establish recommended phase II doses. RESULTS: Sixty patients
      were treated on 12 of 16 possible dosing combinations. Diarrhea was the most
      common drug-related (93%) and dose-limiting toxicity (DLT), constituting four of
      10 DLTs. Dose-limiting grade 3 metabolic abnormalities were also observed. Other
      frequent drug-related toxicities included nausea, stomatitis (both 53%), and
      anemia (48%). Two maximum-tolerated dose combinations were identified: 200 mg of
      neratinib/25 mg of temsirolimus and 160 mg of neratinib/50 mg of temsirolimus.
      Responses were noted in patients with HER2-amplified breast cancer resistant to
      trastuzumab, HER2-mutant non-small-cell lung cancer, and tumor types without
      identified mutations in the HER-PI3K-mTOR pathway. CONCLUSION: The combination of
      neratinib and temsirolimus was tolerable and demonstrated antitumor activity in
      multiple tumor types, warranting further evaluation.

PMID- 24323027
TI  - Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of
      60 patients.
AB  - PURPOSE: Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a
      recently described clinicopathologic entity that usually presents as an effusion
      associated fibrous capsule surrounding an implant. Less frequently, it presents
      as a mass. The natural history of this disease and long-term outcomes are
      unknown. PATIENTS AND METHODS: We reviewed the literature for all published cases
      of breast implant-associated ALCL from 1997 to December 2012 and contacted
      corresponding authors to update clinical follow-up. RESULTS: The median overall
      survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0
      14 years). Capsulectomy and implant removal was performed on 56 of 60 patients
      (93%). Therapeutic data were available for 55 patients: 39 patients (78%)
      received systemic chemotherapy, and of the 16 patients (28%) who did not receive
      chemotherapy, 12 patients opted for watchful waiting and four patients received
      radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined
      by the fibrous capsule achieved complete remission, compared with complete
      remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast
      mass had worse OS and progression-free survival (PFS; P = .052 and P = .03,
      respectively). The OS or PFS were similar between patients who received and did
      not receive chemotherapy (P = .44 and P = .28, respectively). CONCLUSION: Most
      patients with breast implant-associated ALCL who had disease confined within the
      fibrous capsule achieved complete remission. Proper management for these patients
      may be limited to capsulectomy and implant removal. Patients who present with a
      mass have a more aggressive clinical course that may be fatal, justifying
      cytotoxic chemotherapy in addition to removal of implants.

PMID- 24323029
TI  - Recurrence of breast cancer in elderly women.

PMID- 24323028
TI  - Integrative and comparative genomic analysis of lung squamous cell carcinomas in
      East Asian patients.
AB  - PURPOSE: Lung squamous cell carcinoma (SCC) is the second most prevalent type of
      lung cancer. Currently, no targeted therapeutics are approved for treatment of
      this cancer, largely because of a lack of systematic understanding of the
      molecular pathogenesis of the disease. To identify therapeutic targets and
      perform comparative analyses of lung SCC, we probed somatic genome alterations of
      lung SCC by using samples from Korean patients. PATIENTS AND METHODS: We
      performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean
      patients and matched normal DNA. In addition, copy-number analysis and
      transcriptome analysis were conducted for a subset of these samples. Clinical
      association with cancer-specific somatic alterations was investigated. RESULTS:
      This cancer cohort is characterized by a high mutational burden with an average
      of 261 somatic exonic mutations per tumor and a mutational spectrum showing a
      signature of exposure to cigarette smoke. Seven genes demonstrated statistical
      enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA).
      Comparative analysis between Korean and North American lung SCC samples
      demonstrated a similar spectrum of alterations in these two populations in
      contrast to the differences seen in lung adenocarcinoma. We also uncovered
      recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung
      SCC. CONCLUSION: These findings provide new steps toward the identification of
      genomic target candidates for precision medicine in lung SCC, a disease with
      significant unmet medical needs.

PMID- 24323030
TI  - Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed
      emesis in patients with breast cancer: a randomized double-blind study.
AB  - PURPOSE: A combination of aprepitant, a 5-HT3 receptor antagonist, and
      dexamethasone is recommended for the prophylaxis of acute or delayed emesis
      induced by chemotherapy containing anthracyclines plus cyclophosphamide in
      patients with breast cancer. The aim of this study was to verify whether
      dexamethasone is superior to aprepitant in preventing delayed emesis in patients
      receiving the same prophylaxis for acute emesis. PATIENTS AND METHODS: A
      randomized double-blind study comparing aprepitant versus dexamethasone was
      completed in chemotherapy-naive patients with breast cancer treated with
      anthracyclines plus cyclophosphamide. Before chemotherapy, all patients were
      treated with intravenous palonosetron 0.25 mg, dexamethasone 8 mg, and oral
      aprepitant 125 mg. On days 2 and 3, patients randomly received oral dexamethasone
      4 mg twice per day or aprepitant 80 mg once per day. Primary end point was rate
      of complete response (ie, no vomiting or rescue treatment) from days 2 to 5 after
      chemotherapy. RESULTS: Of 580 enrolled patients, 551 were evaluable: 273 received
      dexamethasone, and 278 received aprepitant. Day 1 complete response rates were
      similar: 87.6% for dexamethasone and 84.9% for aprepitant (P < .39). From days 2
      to 5, complete response rates were the same with both antiemetic prophylaxes
      (79.5%; P < 1.00), as were results of secondary end points (ie, complete
      protection, total control, no vomiting, no nausea, score of Functional Living
      Index-Emesis; P < .24). Incidences of insomnia (2.9% v 0.4%; P < .02) and
      heartburn (8.1% v 3.6%; P < .03) were significantly greater with dexamethasone on
      days 2 to 5. CONCLUSION: In patients with breast cancer treated with
      anthracycline plus cyclophosphamide chemotherapy and receiving the same
      antiemetic prophylaxis for acute emesis, dexamethasone was not superior to
      aprepitant but instead had similar efficacy and toxicity in preventing delayed
      emesis.

PMID- 24323031
TI  - Reply to D. Serraino et al.

PMID- 24323033
TI  - Race by sex differences in depression symptoms and psychosocial service use among
      non-Hispanic black and white patients with lung cancer.
AB  - PURPOSE: This study examined race by sex differences in depression symptoms and
      psychosocial service use (pastors, social workers, mental health workers, support
      groups) among patients with lung cancer. PATIENTS AND METHODS: The multiregional
      Cancer Care Outcomes Research and Surveillance study surveyed black and white
      adults with stages I to III lung cancer (n = 1,043) about depression symptoms,
      interest in help for mood, and psychosocial service use. Multivariable logistic
      regression was used to evaluate race/sex differences in depression symptoms
      (modified Center for Epidemiologic Studies Depression Scale >= 6) and
      psychosocial service use, independent of demographic, clinical, psychosocial, and
      behavioral covariates. RESULTS: A total of 18.2% screened positive for depression
      symptoms. This proportion was highest among black men (24.7%), followed by white
      women (20.6%), black women (15.8%), and white men (15.0%). In adjusted analyses,
      white women showed greater risk for depression symptoms relative to black women
      (P = .01) and white men (P = .002), with no other differences among groups. Black
      patients were less likely than white patients to receive desired help for mood
      from their doctors (P = .02), regardless of sex. Among all patients, black women
      were most likely to have contact with pastoral care and social work. CONCLUSION:
      Race and sex interacted to predict risk of depression symptoms. Covariates
      accounted for elevated risk among black men. White women showed greater risk than
      black women and white men, independent of covariates. Black patients may
      experience greater barriers to receiving help for mood from their doctors. Race
      by sex differences in contact with psychosocial services highlight potential
      differences in the extent to which services are available, acceptable, and/or
      sought by patients.

PMID- 24323032
TI  - Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of
      patients with endometrial cancer diagnosed at age younger than 60 years optimizes
      triage for population-level germline mismatch repair gene mutation testing.
AB  - PURPOSE: Clinicopathologic data from a population-based endometrial cancer
      cohort, unselected for age or family history, were analyzed to determine the
      optimal scheme for identification of patients with germline mismatch repair (MMR)
      gene mutations. PATIENTS AND METHODS: Endometrial cancers from 702 patients
      recruited into the Australian National Endometrial Cancer Study (ANECS) were
      tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1
      gene promoter methylation in MLH1-deficient cases. MMR mutation testing was
      performed on germline DNA of patients with MMR-protein deficient tumors.
      Prediction of germline mutation status was compared for combinations of tumor
      characteristics, age at diagnosis, and various clinical criteria (Amsterdam,
      Bethesda, Society of Gynecologic Oncology, ANECS). RESULTS: Tumor MMR-protein
      deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR
      deficient cases identified 22 truncating mutations (3% of all cases) and four
      unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111
      cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative.
      A combination of MMR IHC plus MLH1 methylation testing in women younger than 60
      years of age at diagnosis provided the highest positive predictive value for the
      identification of mutation carriers at 46% versus <= 41% for any other criteria
      considered. CONCLUSION: Population-level identification of patients with MMR
      mutation-positive endometrial cancer is optimized by stepwise testing for tumor
      MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in
      individuals with MLH1 IHC loss, and germline mutations in patients exhibiting
      loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1
      methylation.

PMID- 24323034
TI  - Targeted androgen pathway suppression in localized prostate cancer: a pilot
      study.
AB  - PURPOSE: Ligand-mediated activation of the androgen receptor (AR) is critical for
      prostate cancer (PCa) survival and proliferation. The failure to completely
      ablate tissue androgens may limit suppression of PCa growth. We evaluated
      combinations of CYP17A and 5-alpha-reductase inhibitors for reducing prostate
      androgen levels, AR signaling, and PCa volumes. PATIENTS AND METHODS: Thirty-five
      men with intermediate/high-risk clinically localized PCa were randomly assigned
      to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD),
      or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before
      prostatectomy. Controls included patients receiving combined androgen blockade
      with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary
      outcome measure was tissue dihydrotestosterone (DHT) concentration. RESULTS:
      Prostate DHT levels were substantially lower in all experimental arms (0.02 to
      0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the
      greatest percentage decline in serum testosterone, androsterone, and
      dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the
      androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly
      suppressed in benign glands and moderately in malignant glands (P < .05 for all).
      Two patients had pathologic complete response, and nine had <= 0.2 cm(3) of
      residual tumor (defined as a near-complete response), with the largest numbers of
      complete and near-complete responses in the ZBDK group. CONCLUSION: Addition of
      androgen synthesis inhibitors lowers prostate androgens below that achieved with
      standard therapy, but significant AR signaling remains. Tissue-based analysis of
      steroids and AR signaling is critical to informing the search for optimal local
      and systemic control of high-risk prostate cancer.

PMID- 24323035
TI  - Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone
      versus prednisone alone in progressive, metastatic, castration-resistant prostate
      cancer.
AB  - PURPOSE: We evaluated angiogenesis-targeted sunitinib therapy in a randomized,
      double-blind trial of metastatic castration-resistant prostate cancer (mCRPC).
      PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel-based
      chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d
      continuously or placebo. Patients also received oral prednisone 5 mg twice daily.
      The primary end point was overall survival (OS); secondary end points included
      progression-free survival (PFS). Two interim analyses were planned. RESULTS:
      Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or
      placebo (n = 289). The independent data monitoring committee stopped the study
      for futility after the second interim analysis. After a median overall follow-up
      of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and
      placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097;
      stratified log-rank test, P = .168). PFS was significantly improved in the
      sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890;
      stratified log-rank test, P < .001). Toxicity and rates of discontinuations
      because of adverse events (AEs; 27% v 7%) were greater with sunitinib than
      placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%),
      asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent
      grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v
      8%), and neutropenia (6% v < 1%). CONCLUSION: The addition of sunitinib to
      prednisone did not improve OS compared with placebo in docetaxel-refractory
      mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

PMID- 24323036
TI  - Loss of major molecular response as a trigger for restarting tyrosine kinase
      inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who
      have stopped imatinib after durable undetectable disease.
AB  - PURPOSE: More than half of patients with chronic-phase chronic myelogenous
      leukemia (CP-CML) in complete molecular response (CMR) experience molecular
      relapse after imatinib discontinuation. We investigated loss of major molecular
      response (MMR) as a criterion for resuming therapy. PATIENTS AND METHODS: A
      multicenter observational study (A-STIM [According to Stop Imatinib]) evaluating
      MMR persistence was conducted in 80 patients with CP-CML who had stopped imatinib
      after prolonged CMR. RESULTS: Median time from imatinib initiation to
      discontinuation was 79 months (range, 30 to 145 months);median duration of CMR
      before imatinib discontinuation was 41 months (range, 24 to 96 months); median
      follow-up after discontinuation was 31 months (range, 8 to 92 months). Twenty
      nine patients (36%) lost MMR after a median of 4 months off therapy (range, 2 to
      17 months). Cumulative incidence of MMR loss was estimated as 35% (95% CI, 25% to
      46%) at 12 months and 36% (95% CI, 26% to 47%) at 24 months, whereas probability
      of losing CMR was higher. Fluctuation of BCR-ABL transcript levels below the MMR
      threshold (>= two consecutive positive values) was observed in 31% of patients
      after imatinib discontinuation. Treatment-free remission was estimated as 64%
      (95% CI, 54% to 75%) at 12 and 24 months and 61% (95% CI, 51% to 73%) at 36
      months. Median to time to second CMR was estimated as 7.3 months in re-treated
      patients. CONCLUSION: Loss of MMR is a practical and safe criterion for
      restarting therapy in patients with CML with prolonged CMR.

PMID- 24323037
TI  - Adverse event reporting in cancer clinical trial publications.
AB  - PURPOSE: Reporting adverse events is a critical element of a clinical trial
      publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT)
      group generated recommendations regarding the appropriate reporting of adverse
      events. The degree to which these recommendations are followed in oncology
      publications has not been comprehensively evaluated. METHODS: A review of
      citations from PubMed, Medline, and Embase published between Jan 1, 2009 and
      December 31, 2011, identified eligible randomized, controlled phase III trials in
      metastatic solid malignancies. Publications were assessed for 14 adverse event
      reporting elements derived from the CONSORT harms extension statement; a
      completeness score (range, 0 to 14) was calculated by adding the number of
      elements reported. Linear regression analysis identified which publication
      characteristics associated with reporting completeness. RESULTS: A total of 175
      publications, with data for 96,125 patients, were included in the analysis. The
      median completeness score was eight (range, three to 12). Most publications (96%)
      reported only adverse events occurring above a threshold rate or severity, 37%
      did not specify the criteria used to select which adverse events were reported,
      and 88% grouped together adverse events of varying severity. Regression analysis
      revealed that trials without a stated funding source and with an earlier year of
      publication had significantly lower completeness scores. CONCLUSION: Reporting of
      adverse events in oncology publications of randomized trials is suboptimal and
      characterized by substantial selectivity and heterogeneity. The development of
      oncology-specific standards for adverse event reporting should be established to
      ensure consistency and provide critical information required for medical decision
      making.

PMID- 24323038
TI  - Dose-finding trial designs for combination therapies in oncology.

PMID- 24323040
TI  - Pubertal development, spare time activities, and adolescent delinquency: testing
      the contextual amplification hypothesis.
AB  - Extensive evidence supports associations between early pubertal timing and
      adolescent externalizing behavior, but how and under which conditions they are
      linked is not fully understood. In addition, pubertal development is also
      characterized by variations in the relative speed at which individuals mature,
      but studies linking pubertal 'tempo' and outcomes are scarce. This study examined
      the mediating and moderating roles of spare time activities in associations
      between pubertal development and later delinquency, using data from a large
      (4,327 girls, 4,250 boys) longitudinal UK cohort (Avon Longitudinal Study of
      Parents and Children). Self-reports of Tanner stage were available from ages 9 to
      14, spare time activities at age 12 and delinquency at age 15. Pubertal
      development was examined using latent growth models. Spare time activities were
      categorized using factor analyses, yielding four types (hanging out at home,
      hanging out outside, consumerist behavior, and sports/games), which were examined
      as mediators and moderators. Earlier and faster maturation predicted delinquency
      in boys and girls. Spare time activities partially mediated these links such that
      early maturing girls more often engaged in hanging out outside, which placed them
      at greater risk for delinquency. In addition, compared to their later and slower
      maturing counterparts, boys who matured earlier and faster were less likely to
      engage in sports/games, a spare time activity type that is linked to lower
      delinquency risk. No moderation effects were found. The findings extend previous
      research on outcomes of early maturation and show how spare time activities act
      as proxies between pubertal development and delinquency. 

PMID- 24323039
TI  - Focusing on the positive: a review of the role of child positive affect in
      developmental psychopathology.
AB  - This review proposes a transactional model of child positive affect (PA) to
      reflect the ways that PA, in various contexts, may confer both risk and
      protection for psychosocial adjustment. Though research has largely explored the
      ways that low PA relates to maladjustment in youth, much less research has
      focused on the ways that PA can facilitate adjustment, particularly under
      conditions of risk. Yet, theory suggests that a greater emphasis on PA as a
      protective factor is an important endeavor in developmental psychopathology
      research; such conceptual issues are explored in this review. This review also
      seeks to spur a more nuanced approach to the study of child PA through the use of
      increased multi-method, longitudinal assessments as well as the consideration of
      contextual factors. Building upon this research base is important for aiding in
      the development of intervention and prevention efforts that attempt to promote
      positive psychosocial development and mitigate the course of psychopathology in
      youth at risk for PA difficulties.

PMID- 24323041
TI  - Survival and psychomotor development with early betaine treatment in patients
      with severe methylenetetrahydrofolate reductase deficiency.
AB  - IMPORTANCE: The impact of betaine treatment on outcome in patients with severe
      methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear.
      OBJECTIVE: To investigate the effect of betaine treatment on development and
      survival in patients with severe MTHFR deficiency. DATA SOURCES: MEDLINE, EMBASE,
      and Cochrane databases between January 1960 and December 2012. STUDY SELECTION:
      Studies that described patients with severe MTHFR deficiency who received betaine
      treatment. DATA EXTRACTION AND SYNTHESIS: We identified 15 case reports and case
      series, totaling 36 patients. Data included the following: (1) families with 2 or
      more patients with severe MTHFR deficiency, of whom at least 1 received betaine,
      or (2) single patients with severe MTHFR deficiency treated with betaine. To
      define severe MTHFR deficiency, methionine, homocysteine, MTHFR enzyme activity
      in fibroblasts, or mutations (in the MTHFR gene) had to be described as well as
      the effect of treatment (survival and/or psychomotor development). We compared
      the outcome in treated vs untreated patients and early- vs late-treated patients.
      Sensitivity analysis was performed to address definition of early treatment. To
      further assess the impact of treatment on mortality, we performed a subanalysis
      in families with at least 1 untreated deceased patient. MAIN OUTCOMES AND
      MEASURES: Survival and psychomotor development. RESULTS: Eleven of 36 patients
      (31%) died. All deaths occurred in patients who did not receive treatment or in
      patients in whom treatment was delayed. In contrast, all 5 early-treated patients
      survived. Subgroup analysis of patients with deceased siblings-their
      genotypically identical controls-revealed that betaine treatment prevented
      mortality (P = .002). In addition, psychomotor development in surviving patients
      treated with betaine was normal in all 5 early-treated patients but in none of
      the 19 surviving patients with delayed treatment (P < .001). CONCLUSIONS AND
      RELEVANCE: Early betaine treatment prevents mortality and allows normal
      psychomotor development in patients with severe MTHFR deficiency, highlighting
      the importance of timely recognition through newborn screening.

PMID- 24323042
TI  - How to measure pain in neurological conditions? A systematic review of
      psychometric properties and clinical utility of measurement tools.
AB  - OBJECTIVE: To systematically review the psychometric properties and clinical
      utility of measures of pain in neurological conditions. DATA SOURCES: Electronic
      databases (AMED, CINAHL, MEDLINE, PEDro and Web of Knowledge) were searched from
      their inception to February 2013. REVIEW METHODS: Studies investigating any
      measurement tool to assess pain in central nervous system conditions were
      systematically identified. Data about their psychometric properties and clinical
      utility were extracted and analysed independently. The strength of the
      psychometric properties and clinical utility were assessed. RESULTS: A total of
      13 articles met the selection criteria, which assessed 11 measurement tools;
      eight pain rating scales; one Neuropathic Pain Scale; and two measures of pain
      interference with every-day life. Most of the pain rating scales were
      specifically for hemiplegic shoulder pain. None had been sufficiently developed
      to recommend for use in clinical practice or research. Evaluation of reliability
      and the ability to detect change were particularly sparse. Reliability depended
      on the type of tools used. Patients with right hemisphere damage favoured
      verbal/written responses, while people with left hemisphere damage preferred and
      reported more effectively using visual/numeric responses. Validity between
      measures of pain intensity was moderate, while validity with mood or quality of
      life was weak to moderate. CONCLUSION: None of the selected measures of pain have
      been fully developed or evaluated to demonstrate that they provide accurate,
      relevant reproducible information.

PMID- 24323043
TI  - RACK1 modulates NF-kappaB activation by interfering with the interaction between
      TRAF2 and the IKK complex.
AB  - The transcription factor NF-kappaB plays a pivotal role in innate immunity in
      response to a variety of stimuli, and the coordinated regulation of this pathway
      determines the proper host responses to extracellular signals. In this study, we
      identified RACK1 as a novel negative regulator of NF-kappaB signaling, NF-kappaB
      mediated cytokine induction and inflammatory reactions. RACK1 physically
      associates with the IKK complex in a TNF-triggered manner. This interaction
      interferes with the recruitment of the IKK complex to TRAF2, which is a critical
      step for IKK phosphorylation and subsequent activation triggered by TNF. By
      modulating the interaction between TRAF2 and IKK, RACK1 regulates the levels of
      NF-kappaB activation in response to different intensities of stimuli. Our
      findings suggest that RACK1 plays an important role in controlling the
      sensitivity of TNF-triggered NF-kappaB signaling by regulating IKK activation and
      provide new insight into the negative regulation of inflammatory reactions. 

PMID- 24323044
TI  - A novel mechanism underlies caspase-dependent conversion of the dicer
      ribonuclease into a deoxyribonuclease during apoptosis.
AB  - During C. elegans apoptosis, the dicer ribonuclease (DCR-1) is cleaved by the
      cell death protease CED-3 to generate a truncated DCR-1 (tDCR-1) with one and a
      half ribonuclease III (RNase III) domains, converting it into a deoxyribonuclease
      (DNase) that initiates apoptotic chromosome fragmentation. We performed
      biochemical and functional analyses to understand this unexpected RNase to DNase
      conversion. In full-length DCR-1, tDCR-1 DNase activity is suppressed by its N
      terminal DCR-1 sequence. However, not all the sequence elements in the N-terminal
      DCR-1 are required for this suppression. Our deletion analysis reveals that a 20
      residue alpha-helix sequence in DCR-1 appears to define a critical break point
      for the sequence required for suppressing tDCR-1 DNase activity through a
      structure-dependent mechanism. Removal of the N-terminal DCR-1 sequence from tDCR
      1 activates a DNA-binding activity that also requires the one half RNase IIIa
      domain, and enables tDCR-1 to process DNA. Consistently, structural modeling of
      DCR-1 and tDCR-1 suggests that cleavage of DCR-1 by CED-3 may cause a
      conformational change that allows tDCR-1 to bind and process DNA, and may remove
      steric hindrance that blocks DNA access to tDCR-1. Moreover, a new DNase can be
      engineered using different RNase III domains, including the one from bacterial
      RNase III. Our results indicate that very distantly related RNase III enzymes
      have the potential to cleave DNA when processed proteolytically or paired with an
      appropriate partner that facilitates binding to DNA. We suggest the possibility
      that this phenomenon may be extrapolated to other ribonucleases. 

PMID- 24323046
TI  - Premedication with midazolam for urethral catheterization of febrile infants.
AB  - Febrile infants undergoing urethral catheterization (UC) are often not treated
      for pain and distress. The aim was to evaluate the effectiveness of midazolam
      premedication. We compared a convenience sample of infants who underwent UC with
      midazolam with those who did not receive midazolam. Outcome measures were Visual
      Analog Scale assessment, duration of cry, and emergency department length of
      stay. Thirty-two study participants and 18 controls were prospectively enrolled.
      Midazolam premedication showed a 53% decrease in the mean Visual Analog Scale
      score when parents assessed distress (33.6 vs. 71.7, P<0.0001) and a 48% decrease
      when nurses assessed distress (28.7 vs. 55.5, P<0.0002); the median cry duration
      was significantly shorter (0 vs. 240 s). Serious adverse events were not observed
      during sedation and at 48 h after discharge. Study participants had longer
      emergency department length of stay compared with the controls (191.5 vs. 139
      min, P<0.017). In this cohort, midazolam significantly reduced the distress
      associated with UC without causing serious adverse events. 

PMID- 24323047
TI  - Stroke: Improving the management of patients at risk of haemorrhagic stroke.

PMID- 24323045
TI  - Autophagy and human diseases.
AB  - Autophagy is a major intracellular degradative process that delivers cytoplasmic
      materials to the lysosome for degradation. Since the discovery of autophagy
      related (Atg) genes in the 1990s, there has been a proliferation of studies on
      the physiological and pathological roles of autophagy in a variety of autophagy
      knockout models. However, direct evidence of the connections between ATG gene
      dysfunction and human diseases has emerged only recently. There are an increasing
      number of reports showing that mutations in the ATG genes were identified in
      various human diseases such as neurodegenerative diseases, infectious diseases,
      and cancers. Here, we review the major advances in identification of mutations or
      polymorphisms of the ATG genes in human diseases. Current autophagy-modulating
      compounds in clinical trials are also summarized. 

PMID- 24323048
TI  - Neurodegenerative disease: Mapping the natural history of Huntington disease.

PMID- 24323049
TI  - Alzheimer disease: Effects of the APOE epsilon4 allele on brain development.

PMID- 24323050
TI  - Epilepsy: Effects of exposure to antiepileptic drugs during development.

PMID- 24323052
TI  - Neuro-oncology: Stability of medulloblastoma subgroups at tumour recurrence.

PMID- 24323051
TI  - Delayed neurological deterioration after subarachnoid haemorrhage.
AB  - Subarachnoid haemorrhage (SAH) causes early brain injury (EBI) that is mediated
      by effects of transient cerebral ischaemia during bleeding plus effects of the
      subarachnoid blood. Secondary effects of SAH include increased intracranial
      pressure, destruction of brain tissue by intracerebral haemorrhage, brain shift,
      and herniation, all of which contribute to pathology. Many patients survive these
      phenomena, but deteriorate days later from delayed cerebral ischaemia (DCI),
      which causes poor outcome or death in up to 30% of patients with SAH. DCI is
      thought to be caused by the combined effects of angiographic vasospasm,
      arteriolar constriction and thrombosis, cortical spreading ischaemia, and
      processes triggered by EBI. Treatment for DCI includes prophylactic
      administration of nimodipine, and current neurointensive care. Prompt recognition
      of DCI and immediate treatment by means of induced hypertension and balloon or
      pharmacological angioplasty are considered important by many physicians, although
      the evidence to support such approaches is limited. This Review summarizes the
      pathophysiology of DCI after SAH and discusses established treatments for this
      condition. Novel strategies--including drugs such as statins, sodium nitrite,
      albumin, dantrolene, cilostazol, and intracranial delivery of nimodipine or
      magnesium--are also discussed.

PMID- 24323054
TI  - Migraine: Differential effects of placebos in migraine clinical trials.

PMID- 24323055
TI  - Detection of papillomavirus in equine periocular and penile squamous cell
      carcinoma.
AB  - Squamous cell carcinoma (SCC) is the most common tumor arising in the periocular
      and penile areas of horses. Both ultraviolet radiation and papillomaviruses have
      been implicated in the pathogenesis of SCC in various species, including the
      horse. This retrospective study used polymerase chain reaction (PCR) to detect
      papillomavirus DNA in archival biopsy samples from equine periocular and penile
      SCC from 3 different geographic areas (northeast, southeast, and central United
      States). Forty-two periocular SCCs were tested; none contained papillomavirus
      DNA. Twenty-two penile SCCs were tested, and papillomavirus DNA was identified in
      10 (43%) cases. Sequencing of the PCR products revealed homology with Equus
      caballus papillomavirus 2 (EcPV-2). No geographic distribution in the detection
      of papillomavirus was identified. Penile SCCs were significantly more likely to
      be papillomavirus positive than the periocular SCCs (P < 0.001). The role of
      papillomavirus in the development of penile SCC requires further investigation.
      The differing pathogeneses of periocular and penile SCC suggest that the tumors
      may respond differently to treatment. 

PMID- 24323053
TI  - The emerging agenda of stratified medicine in neurology.
AB  - Stratified medicine can reduce the costs of neurological care, bringing benefits
      to both patients and physicians. The availability of routine genetic testing, new
      biomarkers and advanced imaging, as well as new technologies for patient-centred
      data collection, has expanded the potential for patient stratification. Several
      neurology subspecialities, including stroke, epilepsy and behavioural neurology,
      have already applied stratification for disease prognosis, optimization of
      disease management and reduction of treatment-related adverse events.
      Stratification approaches could improve the cost-effectiveness of neurological
      care that involves treatments with high costs or risks of adverse reactions, as
      well as guide the use of emerging, highly individualized therapies. There are
      still major challenges in the development of clinically actionable stratification
      concepts, and practical barriers can limit adoption of these concepts into
      clinical practice. However, improved technologies and disease understanding are
      making more precise stratification practical. We believe that neurologists should
      become leaders in the development and validation of these practices, and that use
      of these approaches should be part of a broader strategy for addressing both the
      growing needs of an ageing population and the rising pressures for rapid
      improvements in the cost-effectiveness of therapeutics. 

PMID- 24323056
TI  - Bromethalin poisoning in a raccoon (Procyon lotor): diagnostic considerations and
      relevance to nontarget wildlife.
AB  - Submission of a raccoon (Procyon lotor) for necropsy following exhaustion at a
      California wildlife care center revealed minimal gross pathologic changes and
      only mild vacuolar changes in the white matter of the brain. Turquoise granular
      material was noted in the gastrointestinal tract and was submitted for
      toxicological testing along with portions of the brain, liver, kidney, and
      mesenteric and perirenal adipose tissues. Testing of the turquoise material for 7
      anticoagulant rodenticides, strychnine, 4-aminopyridine, starlicide, and salts
      revealed none of these compounds; however, desmethylbromethalin was detected by
      high-performance liquid chromatography-tandem mass spectrometry. Other tissues
      were subsequently analyzed; the mesenteric and perirenal adipose tissues
      contained desmethylbromethalin. Desmethylbromethalin is the active metabolite of
      bromethalin, uncouples oxidative phosphorylation, and results in cerebral edema.
      Bromethalin is a rodenticide that is visually indistinguishable from many other
      rodenticides, making identification of poisonings by appearance alone nearly
      impossible. Based on the pathological and toxicological findings, a diagnosis of
      bromethalin toxicosis was established. In cases of wildlife species with unknown
      deaths or inconsistent clinical signs with normal or minimal histological
      findings, bromethalin toxicosis should be considered as a differential. Adipose
      tissue is the tissue of choice and can be easily harvested from a live or
      deceased animal to help confirm or rule out bromethalin exposure or intoxication.

PMID- 24323058
TI  - Association of inflammaging (inflammation + aging) with higher prevalence of OAB
      in elderly population.
AB  - INTRODUCTION: Although epidemiology studies consistently report increased
      prevalence of overactive bladder (OAB) with age, an accurate deciphering of
      causative links between the two entities remains elusive. Studies on aged rodent
      bladder have so far yielded contradictory results on age-associated changes in
      muscarinic receptors, which highlight the challenge posed by species differences
      in understanding OAB pathology. We hypothesized that age-related biochemical
      changes in bladder leading to altered bladder function will be reflected in
      altered urinary proteome of elderly OAB patients. METHODS: Single time point
      urine specimens were obtained from 140 OAB patients in the age range of 25-90
      years of either sex coming routinely to the urology clinics. Eight chemokines in
      urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex
      immunoassay and ELISA. Multivariate and univariate statistical analyses were done
      to determine association of age with urinary chemokines in OAB patients. RESULTS:
      In agreement with age-dependent higher prevalence of OAB, the logistic regression
      of the data also revealed the significant association of OAB symptoms with age
      [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis
      of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth
      factor) in 137 out of 140 OAB patients [Pearson r = 0.274; 95 %CI (0.112-0.422);
      p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte
      chemoattractant protein-1), which was detected in 115 OAB patients, and the
      remaining chemokines were undetectable in nearly two-third of OAB patients
      included in our cohort. CONCLUSIONS: Based on our findings, we postulate that age
      associated biochemical changes may accentuate the inflammation associated with
      OAB. Urinary NGF elevation in elderly OAB patients may be a homeostatic response
      to counter the senescence of bladder nerves and arrest the progression of OAB
      into detrusor hyperactivity with impaired contractility. Likewise, elevation of
      MCP-1 may be related to decreased muscle mass and increased content of adipose
      tissue in bladder of elderly OAB patients. Urinary NGF and MCP-1 can serve as
      surrogate markers for monitoring age-associated biochemical changes and the
      effect of therapeutic interventions in OAB patients.

PMID- 24323059
TI  - Posterior root tear of the medial and lateral meniscus.
AB  - An avulsion of the tibial insertion of the meniscus or a radial tear close to the
      meniscal insertion is defined as a root tear. In clinical practice, the incidence
      of these lesions is often underestimated. However, several biomechanical studies
      have shown that the effect of a root tear is comparable to a total meniscectomy.
      Clinical studies documented progredient arthritic changes following root tears,
      thereby supporting basic science studies. The clinical diagnosis is limited by
      unspecific symptoms. In addition to the diagnostic arthroscopy, MRI is considered
      to be the gold standard of diagnosis of a meniscal root tear. Three different
      direct MRI signs for the diagnosis of a meniscus root tear have been described:
      Radial linear defect in the axial plane, vertical linear defect (truncation sign)
      in the coronal plane, and the so-called ghost meniscus sign in the sagittal
      plane. Meniscal extrusion is also considered to be an indirect sign of a root
      tear, but is less common in lateral root tears. During arthroscopy, the function
      of the meniscus root must be assessed by probing. However, visualization of the
      meniscal insertions is challenging. Refixation of the meniscal root can be
      performed using a transtibial pull-out suture, suture anchors, or side-to-side
      repair. Several short-term studies reported good clinical results after medial or
      lateral root repair. Nevertheless, MRI and second-look arthroscopy revealed high
      rates of incomplete or absent healing, especially for medial root tears. To date,
      most studies are case series with short-term follow-up and level IV evidence.
      Outerbridge grade 3 or 4 chondral lesions and varus malalignment of >5 degrees 
      were found to predict an inferior clinical outcome after medial meniscus root
      repair. Further research is needed to evaluate long-term results and to define
      evident criteria for meniscal root repair. 

PMID- 24323060
TI  - Percutaneous screw fixation for a femoral head fracture: a case report.
AB  - Femoral head fracture associated with hip dislocation is relatively rare but very
      severe injury. Due to its severity and the need of joint exposure for the
      reduction of femoral head fracture, the surgical treatment cannot but accompany
      many complications, including the osteonecrosis of the femoral head, heterotopic
      ossification, and post-traumatic osteoarthritis. We report a case of less
      invasive percutaneous screw fixation for the femoral head fracture with excellent
      clinical result. Post operatively, the fracture was healed, and no acute
      complication was observed. At 4 years post operation, full Harris hip score was
      achieved, and there were no osteonecrosis of the femoral head, no heterotopic
      ossification, and no post-traumatic osteoarthritis. We suggest attempting less
      invasive percutaneous screw fixation for the femoral head fracture.

PMID- 24323061
TI  - Artificial total disc replacement versus fusion for lumbar degenerative disc
      disease: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The purpose of this study is to compare the effectiveness and safety
      of artificial total disc replacement (TDR) with fusion for the treatment of
      lumbar degenerative disc disease (DDD). Spinal fusion is the conventional
      surgical treatment for lumbar DDD. Recently, TDR has been developed to avoid the
      negative effects of the fusion by preserving function of the motion segment.
      Controversy still surrounds regarding whether TDR is better. METHODS: We
      systematically searched six electronic databases (Medline, Embase, Clinical,
      Ovid, BIOSIS and Cochrane registry of controlled clinical trials) to identify
      randomized controlled trials (RCTs) published up to March 2013 in which TDR was
      compared with the fusion for the treatment of lumbar DDD. Effective data were
      extracted after the assessment of methodological quality of the trials. Then, we
      performed the meta-analysis. RESULTS: Seven relevant RCTs with a total of 1,584
      patients were included. TDR was more effective in ODI (MD -5.09; 95% CI [-7.33, 
      2.84]; P < 0.00001), VAS score (MD -5.31; 95% CI [-8.35, -2.28]; P = 0.0006),
      shorter duration of hospitalization (MD -0.82; 95% CI [-1.38, -0.26]; P = 0.004)
      and a greater proportion of willing to choose the same operation again (OR 2.32;
      95% CI [1.69, 3.20]; P < 0.00001). There were no significant differences between
      the two treatment methods regarding operating time (MD -44.16; 95% CI [-94.84,
      6.52]; P = 0.09), blood loss (MD -29.14; 95% CI [-173.22, 114.94]; P = 0.69),
      complications (OR 0.72; 95% CI [0.45, 1.14]; P = 0.16), reoperation rate (OR
      0.83; 95% CI [0.39, 1.77]; P = 0.63) and the proportion of patients who returned
      to full-time/part-time work (OR 1.10; 95% CI [0.86, 1.41]; P = 0.47). CONCLUSION:
      TDR showed significant safety and efficacy comparable to lumbar fusion at 2 year
      follow-up. TDR demonstrated superiorities in improved physical function, reduced
      pain and shortened duration of hospitalization. The benefits of operating time,
      blood loss, motion preservation and the long-term complications are still unable
      to be proved.

PMID- 24323062
TI  - The effect of gentamicin in irrigating solutions on articular infection
      prophylaxis during arthroscopic ACL reconstruction.
AB  - PURPOSE: The purpose of this study was to investigate whether gentamicin
      irrigation solutions provide a potential new tool to prevent joint infection
      after arthroscopic ACL reconstruction. METHODS: In this prospective randomized
      study, 360 consecutive ACL recondition patients were randomized in two groups
      alternately from Feb 2008 to March 2012. In the first group, 180 patients
      underwent ACL reconstruction with a hamstring autograft, preoperative IV
      antibiotics, and normal saline (0.9% sodium chloride) solution. In the second
      group 180 patients underwent ACL reconstruction with a hamstring autograft,
      preoperative IV antibiotics, and normal saline (0.9% sodium chloride solution)
      with added gentamicin (80 mg/L) (group 2). Three patients from group 1 and six
      patients from group 2 were excluded from the study due to loss of follow-up. The
      patients were followed for 6 months and assessed for signs of deep infection.
      RESULTS: In group 1, a total of 4 (2.2%) postoperative septic arthritis cases
      were documented. In group 2, just one postoperative deep infection (septic
      arthritis) was documented (0.57%). Although the rate of septic arthritis in group
      1 was higher than in group 2, statistical analysis showed that the difference
      between using the gentamicin irrigation solution (80 mg/L) and the saline
      solution alone was not significant. CONCLUSIONS: Using gentamicin in irrigating
      solutions during arthroscopic ACL reconstruction surgery does not statistically
      decrease post operation septic arthritis. LEVEL OF EVIDENCE: Therapeutic Level
      II.

PMID- 24323063
TI  - Risk factors for submucosal and lymphovascular invasion in gastric cancer looking
      indicative for endoscopic submucosal dissection.
AB  - BACKGROUND: Submucosal and lymphovascular (SM/LV) invasions of early gastric
      cancer (EGC) are difficult to diagnose accurately prior to endoscopic submucosal
      dissection (ESD), and are occasionally found in resected specimens, requiring
      additional gastrectomy and lymph node dissection. We performed a retrospective
      study to determine the risk factors for SM/LV invasions. METHODS: We analyzed
      clinicopathological data (age, sex, cancer location, gross morphology,
      multifocality, tumor size, histological differentiation, depth of invasion, and
      the presence or absence of lymphovascular invasion) in patients receiving ESD
      between 2007 and 2012 and presenting with EGC of 2.0 cm or smaller in size, a
      differentiated-type adenocarcinoma, and without ulceration. RESULTS: Of 208
      lesions consecutively resected by ESD, 143 lesions in 132 patients were included
      in this study. Submucosal and lymphovascular invasions were detected in 16
      lesions. Multivariate analysis revealed three independent risk factors for SM/LV
      invasions: dominant histology of moderately-differentiated or papillary
      adenocarcinoma, gross type of 0-IIa + IIc or IIc + IIa, and tumor size of >=1.5
      cm. Lesions exhibiting more than two of these three risk factors were associated
      with having a 47 % increased incidence of SM/LV invasion (odds ratio 15; 95 %
      confidence interval 4.6-49.0; P < 0.0001). CONCLUSIONS: Moderately-differentiated
      or papillary adenocarcinoma, 0-IIa + IIc or IIc + IIa, and a tumor size of >=1.5
      cm were identified as independent risk factors for SM/LV invasion among EGCs
      which appeared to be an endoscopically good indication for ESD. Careful
      surveillances including endoscopic ultrasonography or enhanced computed
      tomography might be needed for high risk patients before ESD.

PMID- 24323065
TI  - [What can colorectal cancer centers achieve in the diagnostics and therapy of
      colorectal liver metastases?].
AB  - Successful resection of liver metastases increases overall survival and can even
      be a curative approach in patients with colorectal cancer (CRC) and isolated
      liver metastases. Resection of liver metastases has clearly changed the therapy
      of this group of patients and has become a standard procedure that is being used
      increasingly more. Accordingly, liver metastasis resection has been included in
      the German evidence-based guidelines and also in international guidelines on the
      treatment of CRC. The treatment of colorectal liver metastases requires a
      multidisciplinary team of experts in the disease, including experienced
      radiologists, medical oncologists, radiotherapists, pathologists and surgeons.
      The interdisciplinary approach to the treatment in specialized tumor boards
      staffed by qualified experts is a prerequisite for successful certification as a
      colorectal cancer center by the German Cancer Society. Regular audits ensure that
      these requirements and that defined quality indicators regarding the tumor board
      and primary and secondary liver metastasis resection, are fulfilled. The
      certification system of the colorectal cancer centers requires and promotes
      conditions that allow an optimal and guideline-oriented treatment of colorectal
      liver metastases both at the level of personnel and infrastructure of a given
      center. The high primary and secondary resection rates in these centers testify
      that the multidisciplinary teams are effective. A detailed analysis of the audit
      reports reveals the close collaboration of all partners within the certified
      networks. These networks also comprise external cooperation with highly
      specialized hospitals if and when necessary. However, the annual report of the
      certificated colorectal cancer centers also demonstrates areas for further
      improvements in multidisciplinary cooperation. 

PMID- 24323064
TI  - Preferential localization of gammaH2AX foci in euchromatin of retina rod cells
      after DNA damage induction.
AB  - DNA damage may lead to cell transformation, senescence, or death. Histone H2AX
      phosphorylation, immunodetected as gammaH2AX foci, is an early response to DNA
      damage persisting even after DNA repair. In cycling mammalian cells with
      canonical nuclear architecture, i.e., central euchromatin and peripheral
      heterochromatin, gammaH2AX foci map preferentially to euchromatin. Mice retina
      rods are G0 cells displaying an inverted nuclear architecture 28 days after birth
      (P28). Rod nuclei exhibit one or two central constitutive heterochromatin
      chromocenters encircled by facultative heterochromatin. Euchromatin resides at
      the nuclear periphery, extending to the equator in cells with two chromocenters.
      To assess the impact of chromatin relocation in the localization of DNA damage,
      gammaH2AX and TUNEL foci induced ex vivo by radiomimetic bleomycin were mapped in
      H3K4me3 immunolabeled P28 rod nuclei. A preferential localization of gammaH2AX
      foci in euchromatin was detected together with foci clustering. Besides, a decay
      of H3K4me3 signal at gammaH2AX foci sites was observed. TUNEL and gammaH2AX foci
      exhibited similar localization patterns in BLM-treated rod cells thus excluding
      curtailed access of anti-gammaH2AX antibodies to heterochromatin. Lack of
      gammaH2AX foci in rod chromocenters appears to be unrelated to the occurrence of
      mid-range foci movements. Foci clusters may arise through DNA double-strand break
      proximity, local non-directional chromatin movements or chromatin relaxation.
      H3K4me3 signal reduction at gammaH2AX foci could stem from local chromatin
      decondensation or downregulation of histone H4 methylation. The observed topology
      of DNA damage in retina-differentiated rods indicates that euchromatin is damage
      prone, regardless of the canonical or inverted nuclear architecture of mammalian
      cells.

PMID- 24323066
TI  - [Bilateral adrenalectomy in Cushing's syndrome].

PMID- 24323067
TI  - Local linear estimation of concordance probability with application to covariate
      effects models on association for bivariate failure-time data.
AB  - Bivariate survival analysis has wide applications. In the presence of covariates,
      most literature focuses on studying their effects on the marginal distributions.
      However covariates can also affect the association between the two variables. In
      this article we consider the latter issue by proposing a nonstandard local linear
      estimator for the concordance probability as a function of covariates. Under the
      Clayton copula, the conditional concordance probability has a simple one-to-one
      correspondence with the copula parameter for different data structures including
      those subject to independent or dependent censoring and dependent truncation. The
      proposed method can be used to study how covariates affect the Clayton
      association parameter without specifying marginal regression models. Asymptotic
      properties of the proposed estimators are derived and their finite-sample
      performances are examined via simulations. Finally, for illustration, we apply
      the proposed method to analyze a bone marrow transplant data set. 

PMID- 24323068
TI  - Spondyloarthritis: Gut inflammation in SpA: flagellin joins the dance?

PMID- 24323070
TI  - Osteoarthritis: Targeting Rac1 via microparticle-based drug delivery system
      protects OA cartilage in vivo.

PMID- 24323075
TI  - The cost analysis of flexible ureteroscopic lithotripsy in 302 cases.
AB  - The objective of this study was to audit the cost of flexible ureterorenoscopic
      lithotripsy. The data for 302 consecutive flexible ureteroscopic lithotripsy
      (FURSL) procedure undertaken in our department for renal stone treatment were
      collected retrospectively. The costs associated with performing FURSL, including
      the cost of ancillary equipment were analyzed. This includes the cost of the
      initial purchase of the ureterorenoscopes and the holmium laser equipment. The
      cost of flexible ureterorenoscopy for each lithotripsy procedure (for a total of
      302 FURSL) was $118. Additional cost of ancillary equipment including laser
      device, ureteral access sheath and stone retrival catheter were $156, $231 and
      $611, respectively. In this series, the costs of the ancillary equipment
      including laser exceeded the purchase and maintenance of the flexible
      ureteroscope. The cost of disposables rather than flexible ureteroscope itself
      should be considered in planning the budget.

PMID- 24323074
TI  - Ocular inflammatory diseases associated with rheumatoid arthritis.
AB  - The extra-articular complications of rheumatoid arthritis (RA) include
      ophthalmological manifestations, which can, in some cases, be the first signs of
      the disease. These inflammatory ophthalmological conditions include episcleritis,
      scleritis and peripheral ulcerative keratitis (PUK). RA is the leading cause of
      necrotizing scleritis and of PUK, which are the two most severe ocular conditions
      associated with the disease. These conditions can rapidly threaten ocular
      prognosis and are associated with excess mortality in patients with RA owing to
      their association with systemic vasculitis. Close collaboration between the
      ophthalmologist and the rheumatologist or internal medicine expert is required
      for the diagnosis and therapeutic management of these patients. In this Review,
      we provide an overview of ocular inflammatory diseases in patients with RA with
      particular focus on the diagnosis and current available therapies (including
      biologic agents) for these conditions. Furthermore, we propose a decision tree to
      assist clinicians in their choice of treatment for patients with RA who also have
      ocular inflammatory disease. 

PMID- 24323076
TI  - Probing the specific ion effects of biocompatible hydrated choline ionic liquids
      on lactate oxidase biofunctionality in sensor applications.
AB  - This paper presents an extended study on the ion effects of a series of
      biocompatible hydrated choline based ionic liquids (ILs) on lactate oxidase
      (LOx), an important enzyme in biosensing technology for the in vitro detection of
      lactic acid. Secondary structural analysis revealed changes in the protein
      conformation in hydrated ILs, while thermal unfolding/aggregation dynamics showed
      different profiles in the presence or absence of ILs. Moreover, LOx thermally
      denaturised at 90  degrees C showed residual activity in the presence of chloride
      and dihydrogen phosphate anions. Kinetic and lifetime studies were also
      performed, providing a better understanding of the ion effects of ILs on the
      biocatalytic activity of the enzyme. 

PMID- 24323077
TI  - Prognosis of untreated strokes due to anterior circulation proximal intracranial
      arterial occlusions detected by use of computed tomography angiography.
AB  - IMPORTANCE: Limited data exist regarding the natural history of proximal
      intracranial arterial occlusions. OBJECTIVE To investigate the outcomes of
      patients who had an acute ischemic stroke attributed to an anterior circulation
      proximal intracranial arterial occlusion. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective cohort study at 2 university-based hospitals from 2003 to 2005 in
      which nonenhanced computed tomography scans and computed tomography angiograms
      were obtained at admission of all adult patients suspected of having an ischemic
      stroke in the first 24 hours of symptom onset. EXPOSURE: Anterior circulation
      proximal intracranial arterial occlusion. MAIN OUTCOMES AND MEASURES: Frequency
      of good outcome (defined as a modified Rankin Scale score of <= 2) and mortality
      at 6 months. RESULTS: A total of 126 patients with a unilateral complete
      occlusion of the intracranial internal carotid artery (ICA; 26 patients: median
      National Institutes of Health Stroke Scale [NIHSS] score, 11 [interquartile
      range, 5-17]), of the M1 segment of the middle cerebral artery (MCA; 52 patients:
      median NIHSS score, 13 [interquartile range, 6-16]), or of the M2 segment of the
      MCA (48 patients: median NIHSS score, 7 [interquartile range, 4-15]) were
      included. Of these 3 groups of patients, 10 (38.5%), 20 (38.5%), and 26 (54.2%)
      with ICA, MCA-M1, and MCA-M2 occlusions, respectively, achieved a modified Rankin
      Scale score of 2 or less, and 6 (23.1%), 12 (23.1%), and 10 (20.8%) were dead at
      6 months. Worse outcomes were seen in patients with a baseline NIHSS score of 10
      or higher, with a modified Rankin Scale score of 2 or less achieved in only 7.1%
      (1 of 14), 23.5% (8 of 34), and 22.7% (5 of 22) of patients and mortality rates
      of 35.7% (5 of 14), 32.4% (11 of 34), and 40.9% (9 of 22) among patients with
      ICA, MCA-M1, and MCA-M2 occlusions, respectively. Age (odds ratio, 0.94 [95% CI,
      0.91-0.98]), NIHSS score (odds ratio, 0.73 [95% CI, 0.64-0.83]), and strength of
      leptomeningeal collaterals (odds ratio, 2.37 [95% CI, 1.08-5.20]) were
      independently associated with outcome, whereas the level of proximal intracranial
      arterial occlusion (ICA vs MCA-M1 vs MCA-M2) was not. CONCLUSIONS AND RELEVANCE:
      The natural history of proximal intracranial arterial occlusion is variable, with
      poor outcomes overall. Stroke severity and collateral flow appear to be more
      important than the level of proximal intracranial arterial occlusion in
      determining outcomes. Our results provide useful data for proper patient
      selection and sample size calculations in the design of new clinical trials aimed
      at recanalization therapies.

PMID- 24323078
TI  - Curcumin-mediated cardiac defects in mouse is associated with a reduced histone
      H3 acetylation and reduced expression of cardiac transcription factors.
AB  - Histone acetylation plays an important role in heart development. However, the
      mechanism(s) remains unclear. This study was designed to evaluate the effect of
      curcumin-caused histone hypo-acetylation on the development of mouse embryonic
      heart and the expression of cardiac transcription factors in vivo. The results
      showed that curcumin treatment significantly decreased histone acetylase activity
      and histone acetylation level in mouse embryonic heart. In curcumin-treated mice,
      the hearts on E11.5 were smaller with thinner ventricular wall and a delayed
      development of trabeculae and ventricular septum compared with the controls. The
      ventricular septum was complete on E14.5; however, the ventricular wall and
      septum were thinner with fewer trabeculae than those in the controls. On E17.5,
      the cardiac structure appeared normal, but the ventricular wall and septum were
      thinner. The expression of GATA4, Nkx2.5 and Mef2c in the heart on E11.5 and
      E14.5 was decreased significantly as compared to the controls. There was no
      significant difference in Mef2c expression on E17.5 between curcumin-treated
      group and the controls, while GATA4 and Nkx2.5 expression remained significantly
      reduced. These results indicate that inhibition of histone acetylation by
      curcumin can reduce the expression of the cardiac transcription factors resulting
      in an abnormal heart development in mice.

PMID- 24323079
TI  - Plasmonic nanomaterials for biodiagnostics.
AB  - The application of nanomaterials to detect disease biomarkers is giving rise to
      ultrasensitive assays, with scientists exploiting the many advantageous physical
      and chemical properties of nanomaterials. The fundamental basis of such work is
      to link unique phenomena that arise at the nanoscale to the presence of a
      specific analyte biomolecule, and to modulate the intensity of such phenomena in
      a ratiometric fashion, in direct proportion with analyte concentration. Precise
      engineering of nanomaterial surfaces is of utmost importance here, as the
      interface between the material and the biological environment is where the key
      interactions occur. In this tutorial review, we discuss the use of plasmonic
      nanomaterials in the development of biodiagnostic tools for the detection of a
      large variety of biomolecular analytes, and how their plasmonic properties give
      rise to tunable optical characteristics and surface enhanced Raman signals. We
      put particular focus on studies that have explored the efficacy of the systems
      using physiological samples in an effort to highlight the clinical potential of
      such assays. 

PMID- 24323080
TI  - Culture-differentiated CD8(+) T cells acquire innate memory-like traits and
      respond to a pathogen-associated molecule.
AB  - Selection of conventional CD4(+) or CD8(+) T cells is usually driven by the
      interaction of double-positive CD4(+)CD8(+) thymocytes with epithelial cells.
      Here, we demonstrate preferential selection of CD8(+) thymocytes from in vitro
      differentiation of CD4(+)CD8(+) double-positive thymocytes exhibiting the
      characteristics of nonconventional innate memory CD8(+) cells. In contrast to
      conventional CD8(+) thymocytes, these culture-differentiated CD8(+) cells are
      eomesodermin positive and robustly express CXCR3, CD44, CD122 and TLR2.
      Interestingly, the pathogen-associated molecule porin promotes preferential
      differentiation of the CD8(+) single-positive subset in association with
      promyelocytic leukemia zinc-finger upregulation and interleukin (IL)-4
      production. On priming with anti-CD3 antibody, porin augmented TLR2 and IFN-gamma
      indicating a role of the TLR ligand in acquisition of innate memory response of
      CD8(+) thymocytes. In addition, porin has a cooperative role with IL-15 on the
      expansion of memory-phenotype CD8(+) T cells along with its effector function.
      Thus, the study opens an avenue to unfold the cues for development of these cells
      and the strategies adopted for bolstering immunity during primary infection. 

PMID- 24323082
TI  - Serum bile acid fractions in neonates on total parenteral nutrition is
      lithocholic acid responsible for the occurrence of cholestasis?
AB  - In order to determine whether lithocholic acid (LCA) contributes to the
      occurrence of total parenteral nutrition (TPN) associated intrahepatic
      cholestasis (IHC) in neonates, we investigated the serum bile acid fractions of
      neonates on TPN. Twenty-five surgical neonates, receiving TPN for more than 2
      weeks were studied. TPN associated IHC was defined as serum defect bilirubin
      greater than 2.0 mg/dL. Serum bile acid fractions were examined by HPLC using
      3alpha -hydroxy steroid dehydrogenase. Eight patients (32%; IHC group) developed
      TPN associated IHC. Serum direct bilirubin concentrations in the non IHC and IHC
      groups were 0.99 and 3.31 mg/dL respectively. Serum total bile acid levels in
      both groups were 14.4 and 71.6 nmol/ml respectively. Glycine and taurine
      conjugated cholic and chenodeoxycholic acids could be detected, and unconjugated
      and secondary (deoxycholic and lithocholic) bile acid were detected in trace
      levels in both the IHC and non-IHC groups. In conclusion, LCA is unlikely to be a
      causative factor in TPN associated IHC in neonates. 

PMID- 24323081
TI  - Induction of antigen-positive cell death by the expression of perforin, but not
      DTa, from a DNA vaccine enhances the immune response.
AB  - The failure of traditional protein-based vaccines to prevent infection by viruses
      such as HIV or hepatitis C highlights the need for novel vaccine strategies. DNA
      vaccines have shown promise in small animal models, and are effective at
      generating anti-viral T cell-mediated immune responses; however, they have proved
      to be poorly immunogenic in clinical trials. We propose that the induction of
      necrosis will enhance the immune response to vaccine antigens encoded by DNA
      vaccines, as necrotic cells are known to release a range of intracellular factors
      that lead to dendritic cell (DC) activation and enhanced cross-presentation of
      antigen. Here we provide evidence that induction of cell death in DNA vaccine
      targeted cells provides an adjuvant effect following intradermal vaccination of
      mice; however, this enhancement of the immune response is dependent on both the
      mechanism and timing of cell death after antigen expression. We report that a DNA
      vaccine encoding the cytolytic protein, perforin, resulted in DC activation,
      enhanced broad and multifunctional CD8 T-cell responses to the HIV-1 antigen GAG
      and reduced viral load following challenge with a chimeric virus, EcoHIV,
      compared with the canonical GAG DNA vaccine. This effect was not observed for a
      DNA vaccine encoding an apoptosis-inducing toxin, DTa, or when the level of
      perforin expression was increased to induce cell death sooner after vaccination.
      Thus, inducing lytic cell death following a threshold level of expression of a
      viral antigen can improve the immunogenicity of DNA vaccines, whereas apoptotic
      cell death has an inhibitory effect on the immune response. 

PMID- 24323083
TI  - The effects of branched-chain amino acid-enriched elemental diet in patients with
      biliary atresia.
AB  - Supplemental administrations of ED-H, branched-chain amino acid (BCAA)-enriched
      elemental diet for hepatic disorder, were performed in 10 postoperative biliary
      atresia (BA) patients. These patients were exhibiting, more or less, cirrhotic
      changes. The duration of ED-H administration ranged from 7 months to 3 years.
      initially, these patients showed lowered molar ratios, Val+Leu+Ile/Phe+Tyr, in
      plasma aminograms with decreased levels of plasma rapid-turnover proteins. ED-H
      administration induced a significant increase in molar ratio as well as increases
      in plasma prealbumin and retinol-binding protein levels. With an improved general
      status, such as activity level and play performance, there were significant
      increases both in weight for age and weight for height. No particular deleterious
      effects were observed throughout the period of ED-H administration. In
      conclusion, supplemental ED-H administration can be performed safely with an
      efficacy in postoperative BA patients who need metabolic/nutritional supports due
      to abnormal liver functions. 

PMID- 24323084
TI  - Evaluation of clinical and biochemical parameters after short term consumption of
      microparticulated protein fat substitute (Simplesse(r)) in a frozen dessert.
AB  - The tolerance of microparticulated protein product (MPP, Simplesse(r)), a protein
      based fat substitute, was evaluated in a randomized, double-blind, three-way
      crossover study using 24 healthy adult subjects (12 males and 12 females). A
      regular cafeteria diet was given alone or together with two 196 ml servings
      (approximately 13 fluid ounces) per day of either super premium ice cream (16%
      butterfat content) or frozen dessert made with MPP for 7 days. The ice cream and
      MPP desserts were administered in a double-blind manner. Three-day dietary
      diaries were maintained for each 7-day period. Routine laboratory tests along
      with plasma lipid panels and amino acid profiles were done prior to study start
      and after each of the three regimens. Vital signs, body weight, and adverse
      experiences were monitored regularly. None of the three regimens had a clinically
      significant effect on routine laboratory tests, body weights, vital signs, or
      plasma amino acid profiles. Of interest, subjects on the ice cream regimen
      experienced statistically significant increases, although within the normal
      range, in plasma total cholesterol, LDL- and HDL-cholesterol, and in
      apolipoprotein A-l and B concentrations compared to either of the other two
      regimens. Two mild gastrointestinal adverse experiences were reported during the
      ice cream regimen. No adverse experiences occurred during the MPP or regular diet
      regimens. Thus, MPP fat substitute is well moderated and can safely be used in a
      low-fat diet regimen. 

PMID- 24323085
TI  - Cereal grains, alpha tocotrienol and cholesterol metabolism in the rat.
AB  - The influence of alpha (alpha)-tocotrienol, the main vitamer of vitamin E in
      barley and oats, on cholesterol synthesis has been studied in laboratory rats.
      Both oats and barley lowered plasma cholesterol relative lo wheat, which had no
      such effect, and the change has been attributed to an inhibitory influence of a 
      tocotrienol on cholesterol synthesis rate. Vitamin E was stripped from oats and
      barley by a petroleum ether extraction procedure and the grains compared with
      their unstripped equivalents. In the oats feeding experiment this resulted in a
      higher plasma cholesterol and lower liver cholesterol synthesis rate. The barley
      experiment produced no significant response. Pure alpha-tocotrienol was gavaged
      into rats fed a semipurified diet without vitamin E, at the rate of 380
      MUg/rat/day for 28 days. There was no significant influence on plasma cholesterol
      level or on liver cholesterol synthesis rate. From these studies it is concluded
      that a -tocotrienol does not influence cholesterol synthesis rate significantly.
      Therefore, it is unlikely lo be a factor in oats and barley responsible for the
      plasma cholesterol lowering observed. 

PMID- 24323086
TI  - Effects of zinc depletion and repletion on natural killer cell activity in aged
      mice.
AB  - The effects of zinc depletion and repletion on spleen natural killer (NK) cell
      activity in aged mice were studied. Sixty 24-month-old male Balb/c mice were
      divided equally into three groups according to their weight: group I were fed the
      zinc-deficient diet (1.3 MUg/g Zn). Group II were fed the zinc-supplemented diet
      (58 MUg/g Zn), but their intake was restricted to the average daily amount
      consumed by the zinc-deficient group and group 111 were fed the zinc-supplemented
      diet (58 MUg/g Zn) ad libitum. After 4 weeks, 10 mice were taken out from each
      group. The determinations of NK cell activity and plasma zinc level were
      performed in aged mice. Then, the other 10 mice in each group were all fed the
      zinc-supplemented diet. After another 4 weeks, they were also killed and used for
      the measurements of NK cell activity and plasma zinc level. The results showed
      that the level of plasma zinc and spleen NK cell activity were both significantly
      lower in zinc-deficient mice than in the restricted mice and in the ad libitum
      controls (P<0.05). There was no statistical difference in plasma zinc level and
      NK cell activity between the restricted mice and the ad libitum controls
      (P>0.05). Supplementation of zinc for 4 weeks enabled a satisfactory recovery of
      all the indices in the zinc-deficient mice. The data suggest that zinc deficiency
      significantly impairs the spleen NK cell activity in aged mice, which can be
      satisfactorily recovered by an adequate zinc supplementation. 

PMID- 24323087
TI  - Critical nutrition events in human history.
AB  - Decisions we make and implement about how people should be fed or feed themselves
      can have far-reaching effects on population, health and ecosystems and not simply
      those of an individual's health or even that of a community. Nutritionists and
      food policy makers are usually preoccupied by the need to optimize health, well
      being and life expectancy in the light of a contemporary analysis of food-health
      relationships. Past pressures to feed human populations in Europe were
      temporarily resolved by the import from the Americas of maize and potatoes or
      sugar production with slave labour in various parts of the world. In China, the
      advent of rice production allowed population growth. In turn, the progressive
      increase in size of these populations has had long-term consequences for
      indigenous food cultures and people across the globe, often with their
      destruction and the reduction of food cultural diversity. Innovations in
      agricultural practice and food technology have also had unintended consequences.
      The development of dairying and dairy technology has contributed to the
      desertification of Africa and the increased fat consumption of Western peoples
      and their changing health patterns. The present rapid changes in the production,
      transport, processing and storage of food may solve some immediate health and
      population problems, but a more sophisticated and long-range analysis is required
      if we are to minimize any adverse effects and encourage a favourable impact on
      the human species and its habitat. 

PMID- 24323088
TI  - The baby-friendly hospital initiative.
AB  - A new global 'baby-friendly hospital initiative' has been launched by UNICEF and
      WHO. Its central elements are hospital practices that are known to protect,
      promote and support breast-feeding. The health benefits of breast-feeding have
      been shown to be more extensive than previously believed. The new initiative is
      needed because the 'code of marketing of breast-milk substitutes' alone has not
      had enough impact on infant-feeding practices. Also, contrary to expectations in
      most parts of the world, the health services have generally been unable to help
      mothers to breast-feed. The 'baby-friendly hospital initiative' employs four
      basic interventions that have been shown to be effective in increasing breast
      feeding: counselling of the mother, early initiation of breast-feeding, rooming
      in and the establishment of support groups for mothers. The main strategy for
      overcoming institutional constraints to breast-feeding is to train the maternity
      health care providers. Also, administrative procedures and public information
      campaigns may be needed. 

PMID- 24323089
TI  - Changing lifestyles and health Background paper for Technical Discussions at 43rd
      Session of Regional Committee, September, 1991, World Health Organization,
      Regional Office for the Western Pacific, Manila, Philippines.
AB  - By early next century a majority of deaths in the countries classed as
      'developing' will be due to chronic non-communicable diseases (NCDs). Such
      countries must now seek to counter the rise of NCDs while continuing the fight
      against traditional killers. 'Lifestyles'--socially sustained styles of living
      viewed in their material aspect--are major determinants of most diseases that
      vary markedly across cultures and through time, not just of those NCDs that
      typically increase with socio-economic modernization. Earlier phases of socio
      economic development also brought with them adverse as well as beneficial effects
      on health. Living in cities greatly increased the transmissibility of infection
      but has since been made compatible with good health. The 'lifestyle diseases'
      associated with socio-economic modernization pose difficult public health
      challenges: they often arise from the otherwise welcome 'first fruits of
      affluence' and there is typically a long delay between the behaviours involved
      and their health effects. Major efforts may be required, over several decades, to
      first contain adverse trends and then to encourage favourable trends. The first
      task may be to help build constituencies for action by documenting and
      publicizing the likely health impact of the elements of lifestyle involved. In
      most industrialized countries, earlier adverse trends in the NCDs have been
      either reversed (heart attack, traffic injuries) or contained (lung cancer) in
      the last 2 decades, showing that such health costs are not a price that must
      inevitably be paid for by the other benefits of modernization. 

PMID- 24323090
TI  - Dimerization of a heat shock protein 90 inhibitor enhances inhibitory activity.
AB  - Heat shock protein 90 (hsp90) accounts for 1-2% of the total proteins in normal
      cells and it functions as a dimer. Hsp90 behaves as a molecular chaperone that
      folds, assembles, and stabilizes client proteins. We have developed a novel hsp90
      inhibitor, and herein we describe the synthesis and biological activity of the
      dimerized variant of this inhibitor. Tethering a monomer inhibitor together
      produced a dimerized compound that more effectively inhibits hsp90 over the
      monomer. 

PMID- 24323091
TI  - Acquisition and visualization techniques for narrow spectral color imaging.
AB  - This paper introduces a new approach in narrow-band imaging (NBI). Existing NBI
      techniques generate images by selecting discrete bands over the full visible
      spectrum or an even wider spectral range. In contrast, here we perform the
      sampling with filters covering a tight spectral window. This image acquisition
      method, named narrow spectral imaging, can be particularly useful when optical
      information is only available within a narrow spectral window, such as in the
      case of deep-water transmittance, which constitutes the principal motivation of
      this work. In this study we demonstrate the potential of the proposed
      photographic technique on nonunderwater scenes recorded under controlled
      conditions. To this end three multilayer narrow bandpass filters were employed,
      which transmit at 440, 456, and 470 nm bluish wavelengths, respectively. Since
      the differences among the images captured in such a narrow spectral window can be
      extremely small, both image acquisition and visualization require a novel
      approach. First, high-bit-depth images were acquired with multilayer narrow-band
      filters either placed in front of the illumination or mounted on the camera lens.
      Second, a color-mapping method is proposed, using which the input data can be
      transformed onto the entire display color gamut with a continuous and
      perceptually nearly uniform mapping, while ensuring optimally high information
      content for human perception.

PMID- 24323092
TI  - Scattering of electromagnetic waves by periodic particle arrays.
AB  - The generalized multiparticle Mie-solution (GMM) is an extension of the well
      known Mie-theory for single homogeneous spheres to the general case of an
      arbitrary ensemble of variously sized and shaped particles. The present work
      explores its specific application to periodic structures, starting from one- and
      two-dimensional regular arrays of identical particles. Emphasis is placed on
      particle arrays with a truncated periodic structure, i.e., periodic arrays (PAs)
      with finite overall dimensions. To predict radiative scattering characteristics
      of a PA with a large number of identical particles within the framework of the
      GMM, it is sufficient to solve interactive scattering for only one single
      component particle, unlike the general case where partial scattered fields must
      be solved for every individual constituent. The total scattering from an array as
      a whole is simply the convolution of the scattering from a single representative
      scattering center with the periodic spatial distribution of all replica
      constituent units, in the terminology of Fourier analysis. Implemented in
      practical calculations, both computing time and computer memory required by the
      special version of GMM formulation applicable to PAs are trivial for ordinary
      desktops and laptops. For illustration, the radiative scattering properties of
      several regular arrays of identical particles at a fixed spatial orientation are
      computed and analyzed. Numerical results obtained from the newly developed
      approach for PAs are compared with those calculated from the general GMM computer
      codes (that have been available online for about a decade). The two sets of
      numerical outputs show no significant relative deviations. However, the CPU time
      required by the specific approach for PAs could drop more than 10,000 times, in
      comparison with the general approach. In addition, an example PA is also
      presented, which consists of as large as 10(8) particles and the general solution
      process is unable to handle.

PMID- 24323093
TI  - Quantization error and dynamic range considerations for compressive imaging
      systems design.
AB  - A natural field of application for compressive sensing theory is imaging. Indeed,
      numerous compressive imaging (CI) systems and applications have been developed
      during the last few years. This work addresses the quantization effect in CI,
      which is fundamental for most CI architectures. In this paper, the implications
      of sensor quantization on universal CI are investigated theoretically and
      demonstrated with numerical experiments. It is shown that employing a CI
      framework may set severe requirements on the quantization depth of the optical
      sensor used. The quantization depth overhead requirement may be prohibitive in
      many optical imaging scenarios employing typical CI architectures. Practical
      solutions that significantly alleviate this requirement are suggested. 

PMID- 24323094
TI  - Polarimetric subtraction of Mueller matrices.
AB  - A general formulation of the additive composition and decomposition of Mueller
      matrices is presented, which is expressed in adequate terms for properly
      performing the "polarimetric subtraction," from a given depolarizing Mueller
      matrix M, of the Mueller matrix of a given nondepolarizing component that is
      incoherently embedded in the whole system represented by M. A general and
      comprehensive procedure for the polarimetric subtraction of depolarizing Mueller
      matrices is also developed. 

PMID- 24323095
TI  - Dynamic model for biospeckle.
AB  - This paper reports the development of a simple dynamic microscopic model to
      describe the main features of the phenomenon known as dynamic speckle, or
      biospeckle. Biospeckle is an interference pattern formed when a biological
      surface is illuminated with coherent light. The dynamic characteristics of
      biospeckle have been investigated as possible tools for assessing the quality of
      biological products. Our model, despite its simplicity, was able to reproduce
      qualitatively the main features of biospeckle. We were able to correlate
      variations in a microscopic parameter associated with movement of the particles
      comprising the organic surface with changes in a macroscopic parameter that
      measures the change rate of a dynamic interference pattern. We showed that this
      correlation occurs only within a limited range of parameter microscope values. We
      also showed how our model was able to describe nonuniform surfaces composed of
      more than one type of particles. 

PMID- 24323096
TI  - Uniform approximation of paraxial flat-topped beams.
AB  - A uniform asymptotic theory of the free-space paraxial propagation of coherent
      flattened Gaussian beams is proposed in the limit of nonsmall Fresnel numbers.
      The pivotal role played by the error function in the mathematical description of
      the related wavefield is stressed. 

PMID- 24323097
TI  - Change in spatial coherence of light on refraction and on reflection.
AB  - A theory of refraction and reflection of partially coherent electromagnetic beams
      has been recently developed. In this paper, we apply it to study the change in
      spatial coherence caused by refraction and by reflection more fully. By
      considering a Gaussian Schell-model beam, we show that the change is, in general,
      dependent on the angle of incidence. 

PMID- 24323098
TI  - Superfocusing of surface plasmon polaritons by metal-coated dielectric probe of
      tilted conical shape.
AB  - By the volume integral equation method, the metal-coated dielectric probes of
      tilted conical shape were investigated for nanofocusing of surface plasmon
      polaritons (SPPs). We consider the cases of incident radially polarized (RP) and
      linearly polarized (LP) Gaussian beams and found that the tilted SPP conical
      probe is valid for both incident linearly and RP beams. Compared to the other
      asymmetric structures reported so far that are valid for incident LP waves, the
      structure proposed in this paper is not only simple but also straightforward to
      obtain the nanofocused localized and enhanced optical field on the tip of
      incident LP beam. 

PMID- 24323099
TI  - Power spectrum model of visual masking: simulations and empirical data.
AB  - In the study of the spatial characteristics of the visual channels, the power
      spectrum model of visual masking is one of the most widely used. When the task is
      to detect a signal masked by visual noise, this classical model assumes that the
      signal and the noise are previously processed by a bank of linear channels and
      that the power of the signal at threshold is proportional to the power of the
      noise passing through the visual channel that mediates detection. The model also
      assumes that this visual channel will have the highest ratio of signal power to
      noise power at its output. According to this, there are masking conditions where
      the highest signal-to-noise ratio (SNR) occurs in a channel centered in a spatial
      frequency different from the spatial frequency of the signal (off-frequency
      looking). Under these conditions the channel mediating detection could vary with
      the type of noise used in the masking experiment and this could affect the
      estimation of the shape and the bandwidth of the visual channels. It is generally
      believed that notched noise, white noise and double bandpass noise prevent off
      frequency looking, and high-pass, low-pass and bandpass noises can promote it
      independently of the channel's shape. In this study, by means of a procedure that
      finds the channel that maximizes the SNR at its output, we performed numerical
      simulations using the power spectrum model to study the characteristics of
      masking caused by six types of one-dimensional noise (white, high-pass, low-pass,
      bandpass, notched, and double bandpass) for two types of channel's shape
      (symmetric and asymmetric). Our simulations confirm that (1) high-pass, low-pass,
      and bandpass noises do not prevent the off-frequency looking, (2) white noise
      satisfactorily prevents the off-frequency looking independently of the shape and
      bandwidth of the visual channel, and interestingly we proved for the first time
      that (3) notched and double bandpass noises prevent off-frequency looking only
      when the noise cutoffs around the spatial frequency of the signal match the shape
      of the visual channel (symmetric or asymmetric) involved in the detection. In
      order to test the explanatory power of the model with empirical data, we
      performed six visual masking experiments. We show that this model, with only two
      free parameters, fits the empirical masking data with high precision. Finally, we
      provide equations of the power spectrum model for six masking noises used in the
      simulations and in the experiments.

PMID- 24323100
TI  - Coherent effects in the scattering of light from two-dimensional rough metal
      surfaces.
AB  - We investigate numerically multiple light-scattering phenomena for two
      dimensional randomly rough metallic surfaces, where surface plasmon polaritons
      (SPPs) mediate several surface scattering effects. The scattering problem is
      solved by numerical solution of the reduced Rayleigh equation for reflection. The
      multiple scattering phenomena of enhanced backscattering and enhanced forward
      scattering are observed in the same system, and their presence is due to the
      excitation of SPPs. The numerical results discussed are qualitatively different
      from previous results for one-dimensionally rough surfaces, as one-dimensional
      surfaces have a limited influence on the polarization of light. 

PMID- 24323101
TI  - Small animal optical diffusion tomography with targeted fluorescence.
AB  - Despite the broad impact in medicine that optics can bring, thus far practical
      approaches are limited to weak scatter or near-surface monitoring. We show a
      method that utilizes a laser topography scan and a diffusion equation model to
      describe the photon transport, together with a multiresolution unstructured grid
      solution to the nonlinear optimization measurement functional, that overcomes
      these limitations. We conclude that it is possible to achieve whole body optical
      imaging with a resolution suitable for finding cancer nodules within an organ
      during surgery, with the aid of a targeted imaging agent. 

PMID- 24323102
TI  - Depth inpainting by tensor voting.
AB  - Depth maps captured by range scanning devices or by using optical cameras often
      suffer from missing regions due to occlusions, reflectivity, limited scanning
      area, sensor imperfections, etc. In this paper, we propose a fast and reliable
      algorithm for depth map inpainting using the tensor voting (TV) framework. For
      less complex missing regions, local edge and depth information is utilized for
      synthesizing missing values. The depth variations are modeled by local planes
      using 3D TV, and missing values are estimated using plane equations. For large
      and complex missing regions, we collect and evaluate depth estimates from self
      similar (training) datasets. We align the depth maps of the training set with the
      target (defective) depth map and evaluate the goodness of depth estimates among
      candidate values using 3D TV. We demonstrate the effectiveness of the proposed
      approaches on real as well as synthetic data. 

PMID- 24323103
TI  - Reflective ghost diffraction for objects with rough surfaces.
AB  - Reflective ghost diffraction (GD) for objects with rough surfaces is investigated
      theoretically and numerically. Using a speckle model to describe the reflectivity
      of the object with variable rough surfaces, the incident and reflective angle
      dependent diffraction condition is obtained, and the analytical expression of the
      reflective GD is derived. Numerical simulations are given to show how the height
      variance and correlation length of the object and the reflective angle in the
      experimental scheme can affect the quality of the reflective GD. Specifically, we
      find that the changes of diffraction patterns of both the simple objects and the
      complicated objects are sensitive to parameters such as the reflective angle and
      the surface fluctuation. Additionally, comparative studies on both reflective GD
      and ghost imaging (GI) have also been performed. We find that reflective GI is
      more robust against system parameters than reflective GD. These results may be
      useful for future experimental works. 

PMID- 24323104
TI  - Behavior of obliquely incident vector Bessel beams at planar interfaces.
AB  - We investigate the behavior of full-vector electromagnetic Bessel beams obliquely
      incident at an interface between two electrically different media. We employ a
      Fourier transform domain representation of Bessel beams to determine their
      behavior upon reflection and transmission. This transform, which is geometric in
      nature, consists of elliptical support curves with complex weighting associated
      with them. The behavior of the scattered field at an interface is highly complex,
      owing to its full-vector nature; nevertheless, this behavior has a
      straightforward representation in the transform domain geometry. The analysis
      shows that the reflected field forms a different vector Bessel beam, but in
      general, the transmitted field cannot be represented as a Bessel beam.
      Nevertheless, using this approach, we demonstrate a method to propagate a Bessel
      beam in the refractive medium by launching a non-Bessel beam at the interface.
      Several interesting phenomena related to the behavior of Bessel beams are
      illustrated, such as polarized reflection at Brewster's angle incidence, and the
      Goos-Hanchen and Imbert-Federov shifts in the case of total reflection. 

PMID- 24323105
TI  - Rayleigh-Sommerfeld diffraction formula in k space.
AB  - An angular spectrum representation in three dimensions is used to develop three
      dimensional Fourier forms of the first and second Rayleigh-Sommerfeld diffraction
      formulae and the Kirchhoff diffraction formula. For forward-propagating waves,
      these reduce to three-dimensional Fourier representations for diffraction in the
      forward half-space. 

PMID- 24323106
TI  - Fast and accurate circle detection using gradient-direction-based segmentation.
AB  - We present what is to our knowledge the first-ever fitting-based circle detection
      algorithm, namely, the fast and accurate circle (FACILE) detection algorithm,
      based on gradient-direction-based edge clustering and direct least square
      fitting. Edges are segmented into sections based on gradient directions, and each
      section is validated separately; valid arcs are then fitted and further merged to
      extract more accurate circle information. We implemented the algorithm with the
      C++ language and compared it with four other algorithms. Testing on simulated
      data showed FACILE was far superior to the randomized Hough transform, standard
      Hough transform, and fast circle detection using gradient pair vectors with
      regard to processing speed and detection reliability. Testing on publicly
      available standard datasets showed FACILE outperformed robust and precise
      circular detection, a state-of-art arc detection method, by 35% with regard to
      recognition rate and is also a significant improvement over the latter in
      processing speed. 

PMID- 24323107
TI  - Design of an image restoration algorithm for the TOMBO imaging system.
AB  - The TOMBO system (thin observation module by bound optics) is a multichannel
      subimaging system over a single electronic imaging device. Each subsystem
      provides a low-resolution (LR) image from a unique lateral point of view. By
      estimating the image's lateral position, a high-resolution (HR) image is restored
      from the series of the LR images. This paper proposes an multistage algorithm
      comprised of successive stages, improving difficulties in previous suggested
      schemes. First, the registration algorithm estimates the subchannel shift
      parameters and eliminates bias. Second, we introduce a fast image fusion,
      overcoming visual blockiness artifacts that characterized previously suggested
      schemes. The algorithm fuses the set of sampled subchannel images into a single
      image, providing the reconstruction initial estimate. Third, an edge-sensitive
      quadratic upper bound term to the total variation regulator is suggested. The
      complete algorithm allows the reconstruction of a clean, HR image, in linear
      computation time, by the use of the linear conjugate gradient optimization.
      Finally, we present a simulated comparison between the proposed method and a
      previously suggested image restoration method. The results show that the proposed
      method yields better reconstruction fidelity while eliminating spatial speckle
      artifacts associated with the previously suggested method. 

PMID- 24323108
TI  - Electromagnetic energy within single-resonance chiral metamaterial spheres.
AB  - We derive an exact expression for the time-averaged electromagnetic (EM) energy
      inside a chiral dispersive sphere irradiated by a plane wave. The dispersion
      relations correspond to a chiral metamaterial consisting of uncoupled single
      resonance helical resonators. Using a field decomposition scheme and a general
      expression for the EM energy density in bianisotropic media, we calculate the
      Lorenz-Mie solution for the internal fields in a medium that is simultaneously
      magnetic and chiral. We also obtain an explicit analytical relation between the
      internal EM energy and the absorption cross section. This result is applied to
      demonstrate that strong chirality leads to an off-resonance field enhancement
      within weakly absorbing spheres. 

PMID- 24323109
TI  - Double Zernike expansion of the optical aberration function from its power series
      expansion.
AB  - Various authors have presented the aberration function of an optical system as a
      power series expansion with respect to the ray coordinates in the exit pupil and
      the coordinates of the intersection point with the image field of the optical
      system. In practical applications, for reasons of efficiency and accuracy, an
      expansion with the aid of orthogonal polynomials is preferred for which, since
      the 1980s, orthogonal Zernike polynomials have become the reference. In the
      literature, some conversion schemes of power series coefficients to coefficients
      for the corresponding Zernike polynomial expansion have been given. In this paper
      we present an analytic solution for the conversion problem from a power series
      expansion in three or four dimensions to a double Zernike polynomial expansion.
      The solution pertains to a general optical system with four independent pupil and
      field coordinates and to a system with rotational symmetry in which case three
      independent coordinate combinations have to be considered. The conversion of the
      coefficients is analytically in closed form and the result is independent of a
      specific sampling scheme or sampling density as this is the case for the commonly
      used least squares fitting techniques. Computation schemes are given that allow
      the evaluation of coefficients of arbitrarily high order in pupil and field
      coordinates. 

PMID- 24323110
TI  - Ray-based diffraction calculations using stable aggregates of flexible elements.
AB  - Diffraction effects are incorporated into a ray-based method for wave
      propagation, referred to as stable aggregates of flexible elements (SAFE). SAFE
      is based on the assignment of a Gaussian field contribution to each ray, where
      these contributions are not independent beam solutions of the wave equation. The
      effects of diffraction by planar opaque obstacles (within the Kirchhoff
      approximation) are accounted for by introducing rays emanating from the
      obstacle's edges. The two leading asymptotic terms to the complex amplitudes for
      these contributions are derived. It is shown that this scheme leads to field
      estimates that remain valid and accurate at caustics and shadow boundaries, as
      illustrated by two examples, corresponding to a focused wave in free space and a
      field propagating in a layered inhomogeneous medium. For simplicity, two
      dimensional propagation is considered. 

PMID- 24323111
TI  - Retinal mesopic adaptation model for brightness perception under transient glare.
AB  - A glare source in the visual field modifies the brightness of a test patch
      surrounded by a mesopic background. In this study, we investigated the effect of
      two levels of transient glare on brightness perception for several combinations
      of mesopic reference test luminances (Lts) and background luminances (Lbs). While
      brightness perception was affected by Lb, there were no appreciable effects for
      changes in the Lt. The highest brightness reduction was found for Lbs in the low
      mesopic range. Considering the main proposal that brightness can be inferred from
      contrast and the Lb sets the mesopic luminance adaptation, we hypothesized that
      contrast gain and retinal adaptation mechanisms would act when a transient glare
      source was present in the visual field. A physiology-based model that adequately
      fitted the present and previous results was developed. 

PMID- 24323112
TI  - Brightness perception of unrelated self-luminous colors.
AB  - The perception of brightness of unrelated self-luminous colored stimuli of the
      same luminance has been investigated. The Helmholtz-Kohlrausch (H-K) effect,
      i.e., an increase in brightness perception due to an increase in saturation, is
      clearly observed. This brightness perception is compared with the calculated
      brightness according to six existing vision models, color appearance models, and
      models based on the concept of equivalent luminance. Although these models
      included the H-K effect and half of them were developed to work with unrelated
      colors, none of the models seemed to be able to fully predict the perceived
      brightness. A tentative solution to increase the prediction accuracy of the color
      appearance model CAM97u, developed by Hunt, is presented. 

PMID- 24323113
TI  - Polarization analyzer for all the states of polarization of light using a
      structured polarizer.
AB  - Polarization analyzers are an essential measuring tool to improve the
      characteristics of optical components and optimize them with respect to a useful
      application in optical networks. We describe an instrument of this kind, which
      consists of two crossed birefringent wedges and acts as a continuous structured
      polarizer for all the states of polarization of light. We analyze this device
      theoretically by using the Poincare-sphere and the Jones-matrix method and verify
      our results in a number of experiments with quartz wedges and red filtered light.
      Different realizations of this instrument are discussed, and an application as a
      beam splitter for all the states of polarization is proposed. 

PMID- 24323114
TI  - Imaging sparse metallic cylinders through a local shape function Bayesian
      compressive sensing approach.
AB  - An innovative method for the localization of multiple sparse metallic targets is
      proposed. Starting from the local shape function (LSF) formulation of the inverse
      scattering problem and exploiting the multitask Bayesian compressive sensing (MT
      BCS) paradigm, a two-step approach is described where, after a first estimation
      of the LSF scattering amplitudes, the reconstruction of the metallic objects is
      yielded through a thresholding and voting step. Selected numerical examples are
      presented to analyze the accuracy, the robustness, and the computational
      efficiency of the LSF-MT-BCS technique. 

PMID- 24323115
TI  - Multilevel fast multipole method based on a potential formulation for 3D
      electromagnetic scattering problems.
AB  - A combination of the multilevel fast multipole method (MLFMM) and boundary
      element method (BEM) can solve large scale photonics problems of arbitrary
      geometry. Here, MLFMM-BEM algorithm based on a scalar and vector potential
      formulation, instead of the more conventional electric and magnetic field
      formulations, is described. The method can deal with multiple lossy or lossless
      dielectric objects of arbitrary geometry, be they nested, in contact, or
      dispersed. Several examples are used to demonstrate that this method is able to
      efficiently handle 3D photonic scatterers involving large numbers of unknowns.
      Absorption, scattering, and extinction efficiencies of gold nanoparticle spheres,
      calculated by the MLFMM, are compared with Mie's theory. MLFMM calculations of
      the bistatic radar cross section (RCS) of a gold sphere near the plasmon
      resonance and of a silica coated gold sphere are also compared with Mie theory
      predictions. Finally, the bistatic RCS of a nanoparticle gold-silver heterodimer
      calculated with MLFMM is compared with unmodified BEM calculations. 

PMID- 24323116
TI  - Destructive impact of imperfect beam collimation in extraordinary optical
      transmission.
AB  - We investigate the difference between analytic predictions, numerical
      simulations, and experiments measuring the transmission of energy through
      subwavelength, periodically arranged holes in a metal film. At normal incidence,
      theory predicts a sharp transmission minimum when the wavelength is equal to the
      periodicity, and sharp transmission maxima at one or more nearby wavelengths. In
      experiments, the sharpest maximum from the theory is not observed, while the
      others appear less sharp. In numerical simulations using commercial
      electromagnetic field solvers, we find that the sharpest maximum appears and
      approaches our predictions as the computational resources are increased. To
      determine possible origins of the destruction of the sharp maximum, we
      incorporate additional features in our model. Incorporating imperfect
      conductivity and imperfect periodicity in our model leaves the sharp maximum
      intact. Imperfect collimation, on the other hand, incorporated into the model
      causes the destruction of the sharp maximum as happens in experiments. We provide
      analytic support through an asymptotic calculation for both the existence of the
      sharp maximum and the destructive impact of imperfect collimation. 

PMID- 24323117
TI  - Study of image reconstruction for terahertz indirect holography with quasi-optics
      receiver.
AB  - In this paper, an indirect holographic image reconstruction algorithm was studied
      for terahertz imaging with a quasi-optics receiver. Based on the combination of
      the reciprocity principle and modified quasi-optics theory, analytical
      expressions of the received spatial power distribution and its spectrum are
      obtained for the interference pattern of target wave and reference wave. These
      results clearly give the quantitative relationship between imaging quality and
      the parameters of a Gaussian beam, which provides a good criterion for terahertz
      quasi-optics transceivers design in terahertz off-axis holographic imagers. To
      validate the effectiveness of the proposed analysis method, some imaging results
      with a 0.3 THz prototype system are shown based on electromagnetic simulation.

PMID- 24323118
TI  - Investigation of the antibacterial activity of a short cationic peptide against
      multidrug-resistant Klebsiella pneumoniae and Salmonella typhimurium strains and
      its cytotoxicity on eukaryotic cells.
AB  - With the growing microbial resistance to conventional antimicrobial agents, the
      development of novel and alternative therapeutic strategies are vital. During
      recent years novel peptide antibiotics with broad spectrum activity against many
      Gram-positive and Gram-negative bacteria have been developed. In this study,
      antibacterial activity of CM11 peptide (WKLFKKILKVL-NH2), a short cecropin
      melittin hybrid peptide, is evaluated against antibiotic-resistant strains of
      Klebsiella pneumoniae and Salmonella typhimurium as two important pathogenic
      bacteria. To appraise the antibacterial activity, minimal inhibitory
      concentration (MIC), minimal bactericidal concentration (MBC) and bactericidal
      killing assay were utilized with different concentrations (2-128 mg/L) of
      peptide. To evaluate cytotoxic effect of peptide, viability of RAJI, Hela, SP2/0,
      CHO, LNCAP cell lines and primary murine macrophage cells were also investigated
      with MTT assay in different concentrations (3-24 and 0.5-16 mg/L, respectively).
      MICs of K. pneumoniae and S. typhimurium isolates were in range of 8-16 and 4-16
      mg/L, respectively. In bactericidal killing assay no colonies were observed at 2X
      MIC for K. pneumoniae and S. typhimurium isolates after 80-90 min, respectively.
      Despite the fact that CM11 reveals no significant cytotoxicity on RAJI, Hela,
      SP2/0, and CHO cell lines beneath 6 mg/L at first 24 and 48 h, the viability of
      LNCAP cells are about 50 % at 3 mg/L, which indicates strong cytotoxicity of the
      peptide. In addition, macrophage toxicity by MTT assay showed that LD50 of CM11
      peptide is 12 MUM (16 mg/L) after 48 h while in this concentration after 24 h
      macrophage viability was about 70 %. 

PMID- 24323119
TI  - The combination of 9p21.3 genotype and biomarker profile improves a peripheral
      artery disease risk prediction model.
AB  - Peripheral artery disease (PAD) is a highly morbid condition affecting more than
      8 million Americans. Frequently, PAD patients are unrecognized and therefore do
      not receive appropriate therapies. Therefore, new methods to identify PAD have
      been pursued, but have thus far had only modest success. Here we describe a new
      approach combining genomic and metabolic information to enhance the diagnosis of
      PAD. We measured the genotype of the chromosome 9p21 cardiovascular-risk
      polymorphism rs10757269 as well as the biomarkers C-reactive protein, cystatin C,
      beta2-microglobulin, and plasma glucose in a study population of 393 patients
      undergoing coronary angiography. The rs10757269 allele was associated with PAD
      status (ankle-brachial index < 0.9) independent of biomarkers and traditional
      cardiovascular risk factors (odds ratio = 1.92; 95% confidence interval, 1.29
      2.85). Importantly, compared to a previously validated risk factor-based PAD
      prediction model, the addition of biomarkers and rs10757269 significantly and
      incrementally improved PAD risk prediction as assessed by the net
      reclassification index (NRI = 33.5%; p = 0.001) and integrated discrimination
      improvement (IDI = 0.016; p = 0.017). In conclusion, a model including a panel of
      biomarkers, which includes both genomic information (which is reflective of
      heritable risk) and metabolic information (which integrates environmental
      exposures), predicts the presence or absence of PAD better than established risk
      models, suggesting clinical utility for the diagnosis of PAD.

PMID- 24323120
TI  - Factors predicting incisional surgical site infection in patients undergoing open
      radical cystectomy for bladder cancer.
AB  - BACKGROUND: The risk factors of incisional surgical site infection (iSSI) after
      open radical cystectomy (ORC) have not been fully investigated. The aim of the
      present study is to examine factors correlated with iSSI development after ORC
      with intestinal urinary diversion. METHODS: A total of 178 patients who had
      undergone ORC with intestinal urinary diversion between 2003 and 2012 at our
      institution were included in this retrospective study. Correlations between
      different perioperative factors and iSSI development were determined using
      univariate and multivariate logistic regression analyses. RESULTS: iSSI was
      observed in 53 patients (29.8 %). In the univariate analysis, age, diabetes
      mellitus, thickness of subcutaneous fat (TSF), and allogeneic transfusion were
      significant predictors of iSSI development. Although subcutaneous closed-suction
      drainage (SCSD) was not a significant factor in univariate analysis, SCSD, age,
      and TSF were all finally identified as independent predictors of iSSI development
      (P = 0.020, P < 0.001, and P = 0.022, respectively). Further analyses
      demonstrated that SCSD was frequently used in patients with relatively thick
      subcutaneous fat tissue and that SCSD significantly decreased iSSI development in
      these patients. CONCLUSIONS: Advanced patient age, thick subcutaneous fat tissue,
      and the absence of SCSD were significantly associated with iSSI development in
      bladder cancer patients who underwent ORC with intestinal urinary diversion. SCSD
      may be a useful procedure for iSSI prevention, especially in patients with
      relatively thick subcutaneous fat tissue.

PMID- 24323121
TI  - Visual-spatial learning impairments are associated with hippocampal PSD-95
      protein dysregulation in a mouse model of fragile X syndrome.
AB  - Fragile X syndrome is the most common cause of inherited intellectual disability
      and is caused by the lack of fragile X mental retardation protein (FMRP)
      expression. In-vitro findings in mice and post-mortem autopsies in humans are
      characterized by dendritic spine abnormalities in the absence of Fmrp/FMRP.
      Biochemical and electrophysiological studies have identified postsynaptic density
      protein (PSD)-95 as having an established role in dendritic morphology as well as
      a molecular target of Fmrp. How Fmrp affects the expression of PSD-95 following
      behavioral learning is unknown. In the current study, wild type controls and Fmr1
      knockout mice were trained in a subset of the Hebb-Williams (H-W) mazes. Dorsal
      hippocampal PSD-95 protein levels relative to a stable cytoskeleton protein (beta
      tubulin) were measured. We report a significant upregulation of PSD-95 protein
      levels in wild type mice, whereas training-related protein increases were blunted
      in Fmr1 knockout mice. In addition, there was a significant negative correlation
      between mean total errors on the mazes and PSD-95 protein levels. The coefficient
      of determination indicated that the mean total errors on the H-W mazes accounted
      for 35% of the variance in PSD-95 protein levels. These novel findings suggest
      that reduced PSD-95-associated postsynaptic plasticity may contribute to the
      learning and memory deficits observed in human fragile X syndrome patients. 

PMID- 24323122
TI  - Effects of broadband noise on cortical evoked auditory responses at different
      loudness levels in young adults.
AB  - Young adults with no history of hearing concerns were tested to investigate their
      /da/-evoked cortical auditory evoked potentials (P1-N1-P2) recorded from 32 scalp
      electrodes in the presence and absence of noise at three different loudness
      levels (soft, comfortable, and loud), at a fixed signal-to-noise ratio (+3 dB).
      P1 peak latency significantly increased at soft and loud levels, and N1 and P2
      latencies increased at all three levels in the presence of noise, compared with
      the quiet condition. P1 amplitude was significantly larger in quiet than in noise
      conditions at the loudest level. N1 amplitude was larger in quiet than in noise
      for the soft level only. P2 amplitude was reduced in the presence of noise to a
      similar degree at all loudness levels. The differential effects of noise on P1,
      N1, and P2 suggest differences in auditory processes underlying these peaks. The
      combination of level and signal-to-noise ratio should be considered when using
      cortical auditory evoked potentials as an electrophysiological indicator of
      degraded speech processing. 

PMID- 24323123
TI  - Effects of H2S on the central regulation of respiration in adult rats.
AB  - Hydrogen sulfide (H2S) is a gasotransmitter synthesized from cysteine (Cys) by
      pyridoxal-5'-phosphate-dependent enzymes. We investigated the potential roles of
      H2S in the regulation of central rhythmic respiration in adult rats in vivo.
      Sodium hydrosulfide (NaHS: 2.5 mM, 10 mM, and 5 mM) as a source of exogenous H2S,
      Cys (2.5 mM, 10 mM and 5 mM) as a source of endogenous H2S, 2.5 mM Cys+10 mM
      hydroxylamine (NH2OH), and 10 mM NH2OH, respectively, were
      intracerebroventricularly injected into rats. The rhythmic discharge of the
      diaphragm, including burst duration (BD), burst interval (BI), burst frequency
      (BF), and integrated amplitude (IA), and arterial blood pressure (BP) were
      measured at different time points. The results were analyzed by analysis of
      variance. A total of 2.5 mM NaHS did not significantly affect changes in BD, BI,
      BF, IA, or BP (P>0.05), whereas 2.5 mM Cys significantly altered BD, BI, and BF
      (P<0.05); however, there was no change in IA and BP (P>0.05). A concentration of
      5 mM Cys had effects similar to those of 5 mM NaHS; both induced biphasic
      respiratory responses and changed the BF (P<0.05). A concentration of 10 mM NH2OH
      irreversibly inhibited rhythmic discharge of the diaphragm except for IA. No
      change was seen in BI, BF, IA, or BP (P>0.05) except for BD was temporarily
      decreased (P<0.05) in the 2.5 mM Cys+10 mM NH2OH group. These results suggest
      that exogenous and endogenous H2S may participate in the regulation of
      respiratory activity in adult rats. 

PMID- 24323124
TI  - Characterization of galectin-1-positive cells in the mouse hippocampus.
AB  - Galectin-1 (gal-1) is one of several well-studied proteins from the galectin
      families. It is a 14.5 kDa glycoprotein with a single carbohydrate-binding
      domain. To examine the distribution and properties of gal-1 in the mouse
      hippocampus, we performed immunohistochemistry using an anti-gal-1 antibody. We
      found that most gal-1-positive cells showed both NeuN and beta-tubulin III (Tuj
      1) immunoreactivity (NeuN: 93%, beta-tubulin III: 88%). Furthermore, we clarified
      that 77% of gal-1-positive cells expressed somatostatin, 79% of gal-1-positive
      cells expressed GAD67, 34% of gal-1-positive cells expressed parvalbumin, 5% of
      gal-1-positive cells expressed calretinin, 2% of gal-1-positive cells expressed
      calbindin, and 31% of gal-1-positive cells expressed neuropeptide Y in the mouse
      hippocampus. These results indicate that gal-1 is expressed in interneurons that
      also express beta-tubulin III and gal-1 may be a novel marker for interneuron
      subpopulations in the hippocampus. 

PMID- 24323125
TI  - Effect of interstimulus interval and age on cortical auditory evoked potentials
      in 10-22-week-old infants.
AB  - This study compares cortical auditory evoked potentials (CAEPs) at different
      interstimulus intervals (ISIs) in infants to determine the impact of stimulus
      rate on wave morphology. Infant CAEPs are dominated by a positive peak P1. We
      hypothesized that infant CAEPs would be more adult-like at longer ISI with P1,
      followed by negativity (labelled N450). Participants were 10 typically developing
      infants aged 10-13 weeks (N=4) and 20-22 weeks (N=6). CAEPs were measured in one
      recording session for /da/ in quiet at 55 dB SPL for ISIs of 910, 1820, 3640 and
      4550 ms in a randomized order. Recordings were complete at each ISI for 7-10
      infants. Seven infants who completed all testing in quiet were also tested in
      continuous white noise (+5 dB signal-to-noise ratio) for the shortest ISI. P1 was
      observable in all infants; N450 was only present in the older infants. There
      appeared to be no ISI effect for younger or older infants, which is not
      consistent with ISI findings for adults and older children. The presence of N450
      in the older infants only suggests that cortical maturational differences are
      evident in speech-evoked CAEPs in young infants. There were minimal effects of
      noise on P1 latency and amplitude. Results suggest different effects of ISI for
      very young infants than those observed in older infants and children. CAEPs are
      being used to measure hearing aid effectiveness in young infants and hence it is
      imperative that the effects of factors such as ISI are better understood. 

PMID- 24323126
TI  - Partial information transmission can be found in music attributes.
AB  - Previous studies have proved that partial information transmission can be found
      between intensity and pitch. In our last study, it was demonstrated that the
      timbre attribute can be transmitted as partial information between timbre and
      intensity. We manipulated the two attributes of stimulus, namely, timbre (piano
      vs. violin) and pitch (high vs. low), to find out whether they also have partial
      information transmission. We used the two-choice 'go/no-go' paradigm, which
      included more 'go' trials of timbre. Our result showed that lateralized readiness
      potentials were elicited in 'no-go' trials, which meant that the timbre attribute
      had been transmitted to the response preparation stage before the intensity
      attribute was processed in the stimuli identification stage. This result supports
      the asynchronous discrete coding model in information processing. Therefore, we
      suggest that partial information transmission can be found in music attributes
      including timbre, intensity, and pitch. 

PMID- 24323127
TI  - Sodium butyrate into the insular cortex during conditioned taste-aversion
      acquisition delays aversive taste memory extinction.
AB  - Histone acetylation is one mechanism that promotes gene expression, and it
      increases during learning of various tasks. Specifically, novel taste consumption
      produces an increased acetylation of histone lysine residues in the insular
      cortex (IC), where protein synthesis is crucial during memory consolidation of
      conditioned taste aversion (CTA). However, the role of this elevated histone
      acetylation during CTA learning has not been examined directly. Thus, the present
      study investigated the effects of sodium butyrate (NaBu), a histone deacetylase
      inhibitor, injected into the IC during CTA acquisition. Male Wistar rats, IC
      bilaterally implanted, were injected 60 min before saccharine presentation, with
      a total volume of 0.5 ul of NaBu solution (100, 500, and 10 ug/0.5 ul) or saline;
      30 min later animals were injected intraperitoneally with lithium chloride, a
      malaise-inducing drug. The next day, CTA retrieval was tested. No effects of NaBu
      were observed during acquisition or retrieval, but during extinction trials, a
      significant delay in aversive memory extinction was observed in the group
      injected with the lowest NaBu dose. This result indicates that NaBu in the IC
      strengthens CTA and delays aversive memory extinction, and suggests that histone
      acetylation could increase long-term taste-aversive memory strength. 

PMID- 24323128
TI  - From genomics to imaging-advances along the care continuum.
AB  - 2013 saw the publication of several reports providing insight into a range of
      ongoing issues in bladder cancer, from screening high-risk candidates to using
      blue-light cystoscopy to reduce recurrence. These data will strengthen efforts to
      optimize the detection and treatment of bladder cancer, benefiting patients along
      the cancer continuum.

PMID- 24323129
TI  - Prostate cancer: Open vs laparoscopic vs robotic RP-the biggest study to date.

PMID- 24323130
TI  - Incontinence: Stress urinary incontinence treatment--surgery first?

PMID- 24323132
TI  - Prostate cancer: Localized disease-are most men really suitable for focal
      therapy?

PMID- 24323133
TI  - Clinician-trialist rounds: 20. Shouldn't 'trialists-in-training' rotate through
      RCT-clerkships?

PMID- 24323131
TI  - Fowler's syndrome--a cause of unexplained urinary retention in young women?
AB  - Urinary retention in women is an uncommon and poorly understood condition. In
      1986, Fowler and colleagues described a syndrome in young women with unexplained
      urinary retention associated with polycystic ovary syndrome. The underlying
      abnormality was a poorly relaxing external urethral sphincter that when studied
      using concentric needle electromyography showed a distinct abnormal pattern
      suggesting direct spread of impulses between muscle fibres. These findings were
      subsequently reproduced by other researchers and in larger patient cohorts, but
      remain the subject of much debate. A poorly relaxing sphincter is thought to
      cause increased urethral afferent activity, which inhibits bladder afferent
      signalling leading to poor bladder sensation and detrusor underactivity. Most
      studies of Fowler's syndrome are limited due to small cohorts with no control
      group and a lack of videourodynamic data. Whether Fowler's syndrome represents a
      distinct cause of urinary retention or results from a maladaptive behaviour and
      is similar to dysfunctional voiding is unclear. Application of sacral
      neuromodulation in patients diagnosed with Fowler's syndrome can restore normal
      voiding, in the absence of any effective pharmacotherapy or surgical treatment. 

PMID- 24323134
TI  - Lipid management in chronic kidney disease: synopsis of the Kidney Disease:
      Improving Global Outcomes 2013 clinical practice guideline.
AB  - DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) organization
      developed a clinical practice guideline in 2013 on lipid management and treatment
      of all adults and children with chronic kidney disease (CKD). All forms of CKD
      are included (non-dialysis-dependent, dialysis-dependent, and kidney transplant
      recipients). METHODS: The KDIGO Lipid Guideline Development Work Group defined
      the scope of the guideline, gathered evidence, determined topics for systematic
      review, and graded the quality of evidence that had been summarized by an
      evidence review team. Searches of the English-language literature were conducted
      through August 2011 and supplemented by targeted searches through June 2013.
      Final modification of the guidelines was informed by the KDIGO Board of Directors
      and a public review process involving registered stakeholders. RECOMMENDATIONS:
      The full guideline includes 13 recommendations; a key element was the
      recommendation for statin or statin with ezetimibe treatment of adults aged 50
      years or older with estimated glomerular filtration rates less than 60
      mL/min/1.73 m2 but not treated with long-term dialysis or kidney transplantation.
      This synopsis focuses on 8 recommendations pertinent to assessment of lipid
      status and treatment with a statin-based regimen in adults.

PMID- 24323135
TI  - Protection against Cu(II)-induced oxidative stress and toxicity to Chlorella
      vulgaris by 2,2'-Bipyridine-5,5'-dicarboxylic acid.
AB  - In this study, we evaluated the role of 2,2'-bipyridine-5,5'-dicarboxylic acid
      (Bpy-COOH) in protecting Chlorella vulgaris from the oxidative stress and
      toxicity induced by Cu(II). Both in vivo and in vitro tests were performed.
      Different addition orders of Bpy-COOH and Cu(II) were tried in the former,
      whereas different Bpy-COOH concentrations were used in both experiments. The in
      vivo experiments showed that the production of reactive oxygen species in C.
      pyrenoidosa treated by the addition of Bpy-COOH and Cu(II) in three orders were
      all significantly less than that in cases treated with only Cu(II). In vitro
      tests indicated that peroxidase-like complexes could be formed between Bpy-COOH
      and Cu(II). Based on these results, it could be concluded that the use of Bpy
      COOH could significantly decrease Cu(II) toxicity to algal cells by forming
      peroxidase-like complexes. 

PMID- 24323136
TI  - DNA methylation analysis of CD4+ T cells in patients with psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease that is characterized by
      aberrant cross-talk between keratinocytes and immune cells such as CD4+ T cells,
      resulting in keratinocyte hyperproliferation in the epidermis. DNA methylation,
      one of several epigenetic mechanisms, plays an important role in gene expression
      without changing the DNA sequence. Several studies have suggested the involvement
      of epigenetic regulation in skin lesions from patients with psoriasis. In this
      study, we investigated the genome-wide DNA methylation status of CD4+ T cells in
      patients with psoriasis compared with healthy subjects using methylated DNA
      immunoprecipitation sequencing (MeDIP-Seq). The results of MeDIP-Seq showed that
      the global methylation values of CD4+ T cells are higher in patients with
      psoriasis than in healthy controls, particularly in the promoter regions. Among
      the most hypermethylated genes in the promoter regions, we selected the genes
      whose expression is significantly reduced in the CD4+ T cells of psoriasis
      patients. Studies using the methylation inhibitor 5-azacytidine in vitro
      methylation assays have shown that the differential expression levels were
      associated with the methylation status of each gene. Bisulfite sequencing of the
      transcription start region of phosphatidic acid phosphatase type 2 domain
      containing 3 (PPAPDC3), one of the selected genes, showed hypermethylation in the
      CD4+ T cells of psoriasis patients. These results suggested that the methylation
      status, which is identified by MeDIP-Seq of the genes, was correlated with the
      mRNA expression level of the genes. Collectively, the DNA methylation status in
      CD4+ T cells might be associated with the pathogenesis of psoriasis. 

PMID- 24323137
TI  - Leadership, organizational climate, and working alliance in a children's mental
      health service system.
AB  - The goal of this study was to examine the relationships of transformational
      leadership and organizational climate with working alliance, in a children's
      mental health service system. Using multilevel structural equation modeling, the
      effect of leadership on working alliance was mediated by organizational climate.
      These results suggest that supervisors may be able to impact quality of care
      through improving workplace climate. Organizational factors should be considered
      in efforts to improve public sector services. Understanding these issues is
      important for program leaders, mental health service providers, and consumers
      because they can affect both the way services are delivered and ultimately,
      clinical outcomes. 

PMID- 24323138
TI  - Community child psychiatric medication experiences measured by an internet-based,
      prospective parent survey of retail pharmacy customers.
AB  - One thousand five hundred parents filling a psychiatric prescription for their 6
      18 year old child with a multi-state retail pharmacy chain received a single
      mailed invitation to complete a detailed online survey. 276 parents responded
      (18.4%). 60% of children on medications had a parent rated CBCL scale score in
      the clinically significant range at enrollment (T score >=65), with a similar
      frequency of clinically significant CBCL scores through 15 months of survey
      followup. 47% of medication regimens were noted to be causing persistent side
      effects. This simple community based data collection method can offer a unique
      way to investigate naturalistic treatment outcomes.

PMID- 24323139
TI  - Community participation and belonging among formerly homeless adults with mental
      illness after 12 months of Housing First in Vancouver, British Columbia: a
      randomized controlled trial.
AB  - This study examines community integration among homeless adults with mental
      illness 6 and 12 months after random assignment to Housing First (independent
      apartments or congregate residence) with support services or to treatment as
      usual (TAU). Residence in independent apartments was associated with increased
      'psychological integration' for participants with less severe needs; however, no
      significant improvement in 'physical integration' was observed among any of the
      intervention groups. Analysis of individual items on the Psychological
      Integration subscale revealed that, compared to TAU, participants assigned to
      independent apartments were more likely to endorse statements related to the
      emotional components of community but not statements related to neighboring.
      Participants assigned to the congregate residence were more likely to endorse
      knowing their neighbors, but not interacting with neighbors or the emotional
      components of community. Findings are discussed in terms of housing program as
      well as broader contextual factors.

PMID- 24323140
TI  - The development of a structured schedule for collecting ICF-CY-based information
      on disability in school and preschool children: an action research from Italy.
AB  - The aim of this study was to present the development of an instrument to collect
      disability information in school settings, based on the International
      Classification of Functioning, Disability and Health, Children and Youth version
      (ICF-CY): the ICF-PEI Schedule (ICF-CY-based schedule for Individualized
      Education Plan). Through an action-research process, a group of 14 teachers
      participated in the definition of a comprehensive list of ICF-CY categories,
      which were then used in a pilot test: categories relevant in at least 30% of the
      cases were retained. Teachers also reported the most relevant difficulties they
      had in using the ICF-CY questionnaires: these were discussed in plenary. On the
      basis of a pilot test and teachers' difficulties, a set of structured, easy to
      use and feasible questions for the school context were developed. A total of 118
      ICF-CY categories were included in the preliminary list and 67 were retained. The
      most relevant difficulties in using ICF-CY questionnaires were as follows:
      obtaining reliable information on bodily impairments; using capacity in
      activities and participation; using qualifiers in 'borderline situations'; and
      identifying systems and policies as barriers or facilitators. The ICF-PEI
      Schedule is composed of 62 items, with a simplified rating scale. Teachers are
      asked to rate performance, which is directly observed, and to address which
      environmental factors impact it; thus, environmental factor rating is simplified.
      The ICF-PEI Schedule was drafted as a feasible instrument for school settings to
      collect and exploit functioning and disability data. Teachers can fruitfully
      employ it to assist in the definition of educational objectives and verify them
      longitudinally. 

PMID- 24323141
TI  - Engineering the field emission properties of graphene film by gas adsorbates.
AB  - We study the effect of different gas adsorbates (N2, O2, and CO2) on the field
      emission (FE) properties of graphene film. Our experimental measurements show
      that, except for N2, adsorption of O2 and CO2 reduces the FE current of the
      graphene film. Moreover, the measured FE hysteresis loop is almost quenched after
      adsorbing O2 or CO2. The ab initio calculations quantify the experimental results
      by predicting a larger work function and smaller FE current for the graphene
      system after O2 or CO2 adsorption. In contrast, the change of FE properties in N2
      adsorbed graphene is negligible. A "depolarization electric field model" is then
      proposed to explain the observed FE hysteresis behavior.

PMID- 24323142
TI  - Optimization of planar self-collimating photonic crystals.
AB  - Self-collimation in photonic crystals has received a lot of attention in the
      literature, partly due to recent interest in silicon photonics, yet no
      performance metrics have been proposed. This paper proposes a figure of merit
      (FOM) for self-collimation and outlines a methodical approach for calculating it.
      Performance metrics include bandwidth, angular acceptance, strength, and an
      overall FOM. Two key contributions of this work include the performance metrics
      and identifying that the optimum frequency for self-collimation is not at the
      inflection point. The FOM is used to optimize a planar photonic crystal composed
      of a square array of cylinders. Conclusions are drawn about how the refractive
      indices and fill fraction of the lattice impact each of the performance metrics.
      The optimization is demonstrated by simulating two spatially variant self
      collimating photonic crystals, where one has a high FOM and the other has a low
      FOM. This work gives optical designers tremendous insight into how to design and
      optimize robust self-collimating photonic crystals, which promises many
      applications in silicon photonics and integrated optics. 

PMID- 24323143
TI  - Coherent backscattering enhancement in refracting media: diffusion approximation.
AB  - The weak localization (coherent backscattering enhancement) phenomenon in media
      with graded refraction index is investigated within the diffusion approximation.
      The obtained analytic results are compared with numerical solutions by finite
      difference and Monte Carlo calculations. 

PMID- 24323144
TI  - Optimizing the precision of a multichannel three-polarizer spectroscopic
      ellipsometer.
AB  - We developed a multichannel three-polarizer spectroscopic ellipsometer based on a
      data acquisition algorithm for achieving optimized precision. This algorithm
      measures unnormalized Fourier coefficients accurately and precisely. Offset
      angles for optical elements were obtained as wavelength-independent values using
      regression calibration. Derived subsets of data reduction functions were used to
      calculate sample parameters. Correlation coefficients of Fourier coefficients
      were used to calculate errors in the sample parameters. Mean standard deviations
      of the sample parameters for each data reduction method were compared to identify
      the best method. This approach could be used to identify suitable precision
      optimization methods for other rotating-element ellipsometers. 

PMID- 24323145
TI  - Scattering by multiple parallel radially stratified infinite cylinders buried in
      a lossy half space.
AB  - The theoretical solution for scattering by an arbitrary configuration of closely
      spaced parallel infinite cylinders buried in a lossy half space is presented in
      this paper. The refractive index and permeability of the half space and cylinders
      are complex in general. Each cylinder is radially stratified with a distinct
      complex refractive index and permeability. The incident radiation is an
      arbitrarily polarized plane wave propagating in the plane normal to the axes of
      the cylinders. Analytic solutions are derived for the electric and magnetic
      fields and the Poynting vector of backscattered radiation emerging from the half
      space. Numerical examples are presented to illustrate the application of the
      scattering solution to calculate backscattering from a lossy half space
      containing multiple homogeneous and radially stratified cylinders at various
      depths and different angles of incidence. 

PMID- 24323146
TI  - Insights into the dependent-scattering contributions to the extinction
      coefficient in highly scattering suspensions.
AB  - We study theoretically the extinction of collimated light in random systems of
      highly scattering particles embedded in nonabsorbing media. We aim to provide
      rough guidelines on the behavior of the extinction coefficient in the so-called
      dependent-scattering regime. We base our analysis on Keller's second order
      perturbative approximation to the effective propagation constant. To gain
      physical insight, we also analyze a simple model based on the physical notion
      that particles in a dense system scatter light in an effective medium. 

PMID- 24323147
TI  - Shot noise statistics and information theory of sensitivity limits in frequency
      modulated continuous-wave ladar.
AB  - A theoretical analysis and experimental verification of the sensitivity limits of
      frequency-modulated continuous-wave (FMCW) ladar in the limit of a strong local
      oscillator is presented. The single-photon sensitivity of coherent heterodyne
      detection in this shot-noise dominated limit is verified to extend to linearly
      chirped waveforms. An information theoretic analysis is presented to estimate the
      information efficiency of received photons for the task of locating the range to
      single and multiple targets. It is found that the optimum receive signal level is
      proportional to the logarithm of the number of resolvable range locations and the
      maximum theoretical photon information efficiency for FMCW ranging with coherent
      fields is log(e)~1.44 bits per received photon. 

PMID- 24323148
TI  - Hydrodynamics of the turbulent point-spread function.
AB  - We derive hydrodynamic equations for the point-spread function of an imaging
      system looking through atmospheric turbulence at an incoherent object. These are
      derived from the hydrodynamics of the index of refraction of the air. We use the
      path integral representation of the paraxial approximation for wave propagation
      through turbulence. We then study the case of a frozen turbulent refractive index
      field being advected past the imaging system with a constant wind and discuss the
      implications for optical flow estimation. We conclude by discussing possible
      directions for future work. 

PMID- 24323149
TI  - Formation of polarization-symmetrical beams using cube-corner reflectors.
AB  - We consider the basic properties and features of beams with a defined type of
      polarization symmetry, in particular beams formed by Laguerre-Gauss modes of the
      second-order. On the whole the polarization structure of such beams does not have
      a certain polarization state. We have shown the approach to such beams' formation
      with the use of cube-corner reflectors, with the faces having a special
      dielectric interference coating. 

PMID- 24323150
TI  - Nonparaxial propagation properties of a vector partially coherent dark hollow
      beam.
AB  - Based on the generalized Raleigh-Sommerfeld diffraction integrals, analytical
      nonparaxial propagation formulas for the elements of the cross-spectral density
      matrix of a vector partially coherent dark hollow beam (DHB) in free space are
      derived. The effect of spatial coherence and beam waist sizes on the statistical
      properties of a nonparaxial vector DHB is studied numerically. It is found that
      one can modulate the statistical properties of a nonparaxial vector DHB by
      varying its initial spatial coherence, which will be useful in some applications
      where nonparaxial beams are commonly encountered. 

PMID- 24323151
TI  - Closed-form analytical solutions for ray tracing in optically anisotropic
      inhomogeneous media.
AB  - Closed-form analytical solutions are obtained for ray tracing in several types of
      optically anisotropic inhomogeneous media whose optical properties are
      characterized by a matrix form of the inhomogeneous dielectric tensor in
      principal coordinates. The first solution is for anisotropic axial media, the
      second solution is for meridional rays in epsilon-negative metamaterial, and the
      third solution is an approximate one for rectangular lenses fabricated by molding
      procedures. The validation of numerical ray-tracing procedures for optically
      anisotropic inhomogeneous media was widely ignored since the solution was not
      available, and thus the present solutions are also useful for the validation.
      Furthermore, as examples of validation, ray trajectories are calculated by the
      closed-form solutions, and their results are compared with those obtained by a
      numerical solution of the geodesic equation which can be interpreted as a
      generalized ray equation. 

PMID- 24323153
TI  - Propagation equation of Hermite-Gauss beams through a complex optical system with
      apertures and its application to focal shift.
AB  - Based on the generalized Huygens-Fresnel diffraction integral (Collins' formula),
      the propagation equation of Hermite-Gauss beams through a complex optical system
      with a limiting aperture is derived. The elements of the optical system may be
      all those characterized by an ABCD ray-transfer matrix, as well as any kind of
      apertures represented by complex transmittance functions. To obtain the
      analytical expression, we expand the aperture transmittance function into a
      finite sum of complex Gaussian functions. Thus the limiting aperture is expressed
      as a superposition of a series of Gaussian-shaped limiting apertures. The
      advantage of this treatment is that we can treat almost all kinds of apertures in
      theory. As application, we define the width of the beam and the focal plane using
      an encircled-energy criterion and calculate the intensity distribution of Hermite
      Gauss beams at the actual focus of an aperture lens. 

PMID- 24323154
TI  - Nonlocal optical effects on the Goos-Hanchen shift at an interface of a composite
      material of metallic nanoparticles.
AB  - We present a theoretical study on the nonlocal optical effects on the Goos
      Hanchen (GH) shift of reflected light from a composite material of metallic
      nanoparticles (MNPs). Using different nonlocal effective medium models, it is
      observed that such effects can be significant for small MNP of sizes down to a
      few nanometers. For small metallic volume fractions, the composite behaves like
      dielectric and the nonlocal effects lead to significant different Brewster
      angles, at which large negative GH shifts take place. For larger volume fractions
      or shorter wavelengths, the composite behaves more like metals and the nonlocal
      effects also lead to different Brewster angles but at values close to grazing
      incidence. These results will have significant implications in the application of
      different effective medium models for the characterization of these nanometallic
      composites when the MNPs are down to a few nanometers in size. 

PMID- 24323155
TI  - Statistical quantification of the effects of viewing distance on texture
      perception.
AB  - In general, viewers are more attracted to local features in images at a shorter
      viewing distance and to global features in images at a longer viewing distance.
      However, numerical analysis of the effect of viewing distance on human texture
      perception and how the perception of global and local changes under certain
      conditions are still undetermined. In this paper, we present statistical
      prediction of the relationship between the domination ratio of global and local
      features and the viewing distances under the control of several factors, using
      the logistic regression model. We synthesized textures by separately controlling
      global and local textural features using a texture model based on mathematical
      morphology, namely the primitive, grain, and point configuration texture model.
      Visual sensory tests were carried out on 80 subjects during two sets of
      experiments. The collected data were statistically analyzed using logistic
      regression and Akaike information criteria. Besides the main factor of viewing
      distance, the factors including gender, changing the order of viewing positions,
      and prior knowledge were also shown quantitatively to have significant influence
      on human texture perception. Our results showed that (1) local features of a
      texture were more attractive to females than males, (2) the first impression
      might have affected subsequent decisions in texture perception, and (3) subjects
      who had prior knowledge (supervised) were more sensitive to the changes in global
      and local dominance. (4) Regarding the interactions of the factors, prior
      knowledge reduced the effects of individual differences and perception condition
      differences on human texture perception. This study is dedicated to the
      construction of numerical relationships between viewing distance and human
      texture perception as well as to cognitive investigation of biases in global and
      local perceptions.

PMID- 24323156
TI  - Two-dimensional Airy-like beam generation by coupling waveguides.
AB  - We propose and demonstrate a two-dimensional (2D) Airy-like beam generation
      technique based on arrayed waveguides. We show that the output beams with quasi
      Airy amplitude and cubic-like phase from an arrayed waveguide end have 2D Airy
      like patterns. These beams have the ability to remain quasi-nondiffracting,
      transverse accelerating, and self-healing during propagation. We also analyze
      wave propagation along this arrayed waveguide using coupled-mode theory and the
      beam propagation method. 

PMID- 24323157
TI  - Pulsed ultrasound modulated optical tomography with harmonic lock-in holography
      detection.
AB  - A method that uses digital heterodyne holography reconstruction to extract
      scattered light modulated by a single-cycle ultrasound (US) burst is demonstrated
      and analyzed. An US burst is used to shift the pulsed laser frequency by a series
      of discrete harmonic frequencies which are then locked on a CCD. The analysis
      demonstrates that the unmodulated light's contribution to the detected signal can
      be canceled by appropriate selection of the pulse repetition frequency. It is
      also shown that the modulated signal can be maximized by selecting a pulse
      sequence which consists of a pulse followed by its inverted counterpart. The
      system is used to image a 12 mm thick chicken breast with 2 mm wide optically
      absorbing objects embedded at the midplane. Furthermore, the method can be
      revised to detect the nonlinear US modulated signal by locking at the second
      harmonic US frequency.

PMID- 24323158
TI  - Retinal light distributions, the Stiles-Crawford effect and apodization.
AB  - Analysis of retinal image formation for beams of coherent and incoherent
      radiation emphasizes the role of the Poynting vector's inclination with respect
      to the retinal image plane. Coherent beams interfere and give rise to a single
      Poynting vector that highlights the unique direction of incidence of energy flow,
      whereas multiple incoherent beams, especially incoherent extended sources in the
      pupil, generate electro-magnetic disturbances in the image plane each
      characterized by Poynting vectors of their own. As a result, the Stiles-Crawford
      diminution of luminant efficiency adds differently depending on the coherence of
      the entering light. Two practical considerations follow: first, in performing
      diffraction calculations for the retinal image from known wavefronts in the pupil
      plane, apodization terms should not be factored in, and, second, in principle,
      for perfect imaging in standard target viewing, Stiles-Crawford integration with
      increasing pupil diameter is not expected. 

PMID- 24323159
TI  - Role of intensity fluctuations in third-order correlation double-slit
      interference of thermal light.
AB  - A third-order double-slit interference experiment with a pseudothermal light
      source in the high-intensity limit has been performed by actually recording the
      intensities in three optical paths. It is shown that not only can the visibility
      be dramatically enhanced compared to the second-order case as previously
      theoretically predicted and shown experimentally, but also that the higher
      visibility is a consequence of the contribution of third-order correlation
      interaction terms, which is equal to the sum of all contributions from second
      order correlation. It is interesting that, when the two reference detectors are
      scanned in opposite directions, negative values for the third-order correlation
      term of the intensity fluctuations may appear. The phenomenon can be completely
      explained by the theory of classical statistical optics and is the first concrete
      demonstration of the influence of the third-order correlation terms. 

PMID- 24323160
TI  - Rigorous analytical modeling of high-aperture focusing through a spherical
      interface.
AB  - High-aperture focusing through a spherical interface has been employed in optical
      data storage, photolithography, and especially microscopy. This paper first forms
      an approximate model, based on geometrical optics and Fourier optics, for
      evaluating focal fields of the focusing systems. This approximate model helps to
      clarify some doubts existing in literature. We then propose a rigorous model that
      is applicable to more general systems. Our model is based on multipole theory,
      which expands the electromagnetic fields into spherical harmonics. 

PMID- 24323161
TI  - Echelette optical low-pass filter as a Bangerter filter for diagnosis and
      treatment of amblyopia and diplopia.
AB  - This paper presents a new echelette optical low-pass filter that serves as a
      Bangerter filter (BF) for diagnosis and treatment of amblyopia and diplopia.
      Theoretical analysis and experimental measurements showed that echelette BFs have
      several advantages over the modern BFs used in medicine. Four echelette BFs with
      different grating periods and one BF were manufactured, and image blurring in an
      optical visual system with an echelette BF was experimentally investigated. The
      experimentally measured modulation transfer function and line spread function
      demonstrated definite image blurring (line expansion) that is inversely
      proportional to the width of the grating period. The results of measurements of
      the angular resolution of the optical system with an echelette BF coincide well
      with the results obtained by theory. 

PMID- 24323162
TI  - Improving wavefront reconstruction accuracy by using integration equations with
      higher-order truncation errors in the Southwell geometry.
AB  - Least-squares (LS)-based integration computes the function values by solving a
      set of integration equations (IEs) in LS sense, and is widely used in wavefront
      reconstruction and other fields where the measured data forms a slope. It is
      considered that the applications of IEs with smaller truncation errors (TEs) will
      improve the reconstruction accuracy. This paper proposes a general method based
      on the Taylor theorem to derive all kinds of IEs, and finds that an IE with a
      smaller TE has a higher-order TE. Three specific IEs with higher-order TEs in the
      Southwell geometry are deduced using this method, and three LS-based integration
      algorithms corresponding to these three IEs are formulated. A series of
      simulations demonstrate the validity of applying IEs with higher-order TEs in
      improving reconstruction accuracy. In addition, the IEs with higher-order TEs in
      the Hudgin and Fried geometries are also deduced using the proposed method, and
      the performances of these IEs in wavefront reconstruction are presented. 

PMID- 24323163
TI  - Simple solution to the Fresnel-Kirchoff diffraction integral for application to
      refraction-enhanced radiography.
AB  - We present a simple solution to the Fresnel-Kirchoff diffraction integral that is
      appropriate for x-ray radiography of strongly absorbing and phase-shifting
      objects in the geometrical optics regime, where phase contrast enhancements can
      be considered to be caused by refraction by a semi-opaque object. We demonstrate
      its accuracy by comparison to brute-force numerical ray trace and diffraction
      calculations of a representative simulated object, and show excellent agreement
      for spatial scales corresponding to Fresnel numbers greater than unity. The
      result represents a significant improvement over approximate formulas typically
      used in analysis of refraction-enhanced radiographs, particularly for radiography
      of transient phenomena in objects that strongly refract and show significant
      absorption. 

PMID- 24323164
TI  - Monodisperse magnetic core/shell microspheres with Pd nanoparticles-incorporated
      carbon shells.
AB  - This work reports a hard self-template method to synthesize core/shell like
      Fe3O4@C microparticles, in which the Pd nanocrystals can be alternatively
      incorporated into the carbon shells. The Fe3O4@polyaniline core/shell
      microspheres were first synthesized as the precursor by in situ polymerization of
      aniline onto the surface of the Fe3O4 microspheres. In a subsequent carbonization
      of the precursor under a vacuum oven, the Fe3O4 core was preserved and the
      polyaniline shell transferred into carbon shells enveloping the magnetic sphere,
      forming magnetic Fe3O4@C microspheres. The Pd ions could be impregnated into the
      polyaniline shell, and thus the obtained composites were transformed into
      Fe3O4@C/Pd microspheres under the same vacuum heating progress. The as-obtained
      system demonstrates superparamagnetic characteristics, which would benefit its
      potential application in nanocatalysts. This strategy provides an efficient
      approach for tailoring core/shell materials with desired functionalities and
      structures by adjusting the precursors and structure-directing agents. 

PMID- 24323165
TI  - Enhanced oval window and blocked round window passages for middle-inner ear
      transportation of gadolinium in guinea pigs with a perforated round window
      membrane.
AB  - To elucidate the communication between the middle and inner ear, and the fluid
      dynamics of the inner ear with the perilymphatic fistula (PLF) of the round
      window membrane (RWM). The PLF of the RWM was created in nine guinea pigs.
      Gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) was
      delivered into the middle ear and followed in the inner ear using a 4.7 Tesla
      MRI. Pressure was delivered to the external ear canal of PLF ear in an attempt to
      enhance the inner ear uptake of Gd-DTPA-BMA. The immediate loading of Gd-DTPA-BMA
      in the scala tympani of the basal turn was ablated by the outflow of perilymph
      through the leaking RWM while the oval window passage for Gd-DTPA-BMA was
      enhanced. There was more Gd-DTPA-BMA distribution in the scala tympani than in
      the scala vestibuli in the second turn of the PLF cochlea (within 20 min). Signal
      in the vestibulum and scala vestibuli of the basal turn and rest part of PLF
      cochlea was greater than that of the control cochlea with intact RWM within 30
      min. Pressure applied to the external ear canal tended to enhance the loading of
      Gd-DTPA-BMA in the perilymphatic scalae of the PLF cochlea. The enhanced oval
      window passage of Gd-DTPA-BMA was proven by the distorted distribution in the
      inner ear with PLF. The radial communication of cochlear perilymph was supported
      by the Gd-DTPA-BMA gradient among the perilymphatic scalae. Applying positive
      pressure to the external ear canal caused backflow of perilymph into the cochlea
      which has a potential of transmitting microbes from the middle ear into the inner
      ear.

PMID- 24323166
TI  - The effects of dexamethasone and levobupivacaine on postoperative pain in
      modified radiofrequency assisted uvulopalatoplasty (MRAUP) surgery.
AB  - The objective of this prospective, randomized study was to evaluate the effect of
      pre-emptive local infiltration of lidocaine, lidocaine plus dexamethasone,
      levobupivacaine and levobupivacaine plus dexamethasone on postoperative pain in
      Modified Radiofrequency Assisted Uvulopalatoplasty (MRAUP) cases. Sixty adult
      patients (44 males and 16 females) aged 32-51 years with simple snoring were
      divided into four groups. The anesthesia of the patients in the first group was
      achieved with lidocaine HCl, in the second group, with lidocaine HCl and
      dexamethasone sodium phosphate, in the third group, with levobupivacaine, and in
      the fourth group, levobupivacaine and dexamethasone sodium phosphate. All the
      patients were applied Modified Radiofrequency Assisted Uvulopalatoplasty
      technique. The pain experienced by the patients during swallowing and at rest on
      the 1st, 3rd, 5th, 7th, and 10th day and analgesic consumption were evaluated
      using standard 10 cm visual analog scales. The mean duration of operation in the
      group that received lidocaine HCl was 22 +/- 3 min, while in the group that
      received levobupivacaine HCl was 27 +/- 4 min. There were statistically
      significant differences between the groups for analgesic effects on the 1st, 3rd,
      5th, and 7th day and for the amount of analgesics used, on the 1st, 3rd, and 5th
      day. The best results were obtained in the group that received levobupivacaine
      HCl and steroid (p < 0.001). Steroid and local anesthetic combinations are
      superior to controls in the management of postoperative pain in MRAUP surgery. 

PMID- 24323168
TI  - Supplementary feeding in programmes in developing countries: lessons of the
      eighties.
AB  - This extensive report reviews the important lessons learned during the 1980s on
      supplementary food distribution for the vulnerable groups in developing
      countries. These lessons may be useful in making such programs a more cost
      effective option in narrowing the food/nutrient gap in intake among the program
      beneficiaries. This report follows a similar report published at the end of the
      1970s by the author and George Beaton for UNICEF. The primary focus in the study
      has been the food distribution among young children, particularly school
      children, and also in pregnant and lactating women. The data have been gathered
      through a comprehensive search of the literature, official reports and documents
      from several United Nations agencies, aid agencies, national and international
      institutions. As well as original research papers on theoretical and applied
      issues, reports on design and evaluation of specific programs in over 20
      countries are studied. Consideration of programme design examines objectives,
      nutrient/food gap, poverty reduction, malnutrition, mother and child feeding
      practices, foods, ration sizes, leakages, targeting, coverage, integration of
      feeding and health care. Potential and measured benefits are considered in the
      light of the reports published at the end of the 1970s and consequent analysis of
      work up until the end of the 1980s. Programme costs are documented. In a
      discussion on context and input, the functional significance of mild and moderate
      malnutrition is considered, together with diet and physical activity. The author
      offers some thoughts on future directions and highlights the need for further
      research. 

PMID- 24323167
TI  - Predictors for outcome of paper patch myringoplasty in patients with chronic
      tympanic membrane perforations.
AB  - The purpose of the present study is to evaluate the outcome of paper patch
      myringoplasty for chronic tympanic membrane (TM) perforations and to explore the
      predictive factors for a successful closure. A retrospective study was performed
      in a tertiary referral center. Data of the patients who met the inclusion
      criteria were analyzed: the treatment outcomes and the potential predictive
      factors including age, sex, the affected ear, hearing level, duration of
      perforation, causes, location and size of perforations, relationship between the
      perforation border and the malleus, status of TM surface, and the number of patch
      applications. Complete closure was achieved in 27 of the total 43 subjects. Among
      the 11 clinical and TM factors, only the perforation size remained significant as
      the predictor after multivariable logistic regression (p = 0.029, OR 4.4). The
      patients with perforation <= 5% of the TM showed higher closure rate (78.3%) than
      those with perforation >5% (45.0%). In conclusion, paper patch myringoplasty
      showed overall success rate of 62.8%. In patients with perforations smaller than
      5% of the TM, the closure rate was 78.3%. The predictor of the treatment outcome
      was the perforation size. We can try paper patch myringoplasty first in patients
      who had dry chronic perforations smaller than 5% of the TM without middle ear
      disease.

PMID- 24323169
TI  - Determination of tocotrienol and tocopherol isomers at physiological
      concentration by HPLC in Caucasian and Japanese women.
AB  - A sensitive, specific and simple method for simultaneous evaluation of tocopherol
      and tocotrienol isomers in human serum by normal phase HPLC with a fluorescence
      detector has been developed. Tocopherol and tocotrienol isomers are measurable in
      physiological concentration in human serum by this method. There is no
      significant difference in serum alpha- and beta-tocopherols and alpha-, gamma-,
      and delta-tocotrienols between Caucasian and Japanese subjects. However, serum
      gamma- and delta-tocopherol concentrations in Japanese women are significantly
      higher than in Caucasian women. 

PMID- 24323170
TI  - Trends and dietary implications of some chronic non-communicable diseases in
      peninsular Malaysia.
AB  - Non-communicable diseases with dietary implications, ischaemic heart disease,
      diabetes mellitus and cancers of the breast and colon are discussed in relation
      to their prevalence and mortality rates in peninsular Malaysia during the past
      few decades. The mortality rate due to diseases of the circulatory system has
      more than doubled since 1970, deaths due to ischaemic heart disease being the
      major cause. The prevalence of diabetes mellitus has risen from 0.65% in 1960 to
      about 4% currently. The mortality risk for both ischaemic heart disease and
      diabetes is highest in the Indian compared to Malay and Chinese populations. The
      Chinese show the highest mortality rate for cancers of the breast and colon. This
      could reflect, partly, because more people especially in the urban areas are
      seeking treatment and improved diagnosis. Empirical dietary data indicate an
      increase in the prevalence of hypercholesterolaemia among urban adults and
      overweight among urban and rural adults. Aggregate data from food balance sheets
      indicate increased availability of energy intake from fats and oils, sugar, and
      animal products, with concomitant decline in available energy from plant
      products. Continued public health education on the important linkage between diet
      and disease is called for. 

PMID- 24323171
TI  - The effects of soluble dietary fibre from the Thai herb, sweet basil seed, on
      human body composition.
AB  - Twenty obese patients, two males and 18 females, with a mean (+/- SEM) age of
      41.7+/- 3.2 years and body mass index (BMI) of 31.8+/- 3.8 kg/m2, were enrolled
      in a 16-week study to evaluate the usefulness and limitations of treatment with a
      sweet basil seed (Ocimum canum, Sims) extract. For 16-week (wk0-wk16), they were
      instructed to reduce their usual energy intake. After baseline observations for 4
      weeks, for 12 wk (wk4-wkl6), patients were asked to ingest 2 g of sweet basil
      seed extract, swollen with 240 ml of water, before lunch and supper (4 g/day).
      Sixteen patients commenced extract use at wk4. On the basis of their ability to
      ingest more or less than 50% of the extract, they were categorized into high dose
      (n= 10) and low dose (n=6) users. In high dose users, there were a significant
      decrease in BMI by the 4th week of treatment which was maintained at the 8th and
      12th weeks of treatment, but skinfold thickness measurements for fat did not
      decrease. There may, therefore, have been a reduction in total body water.
      Further support for this view was provided by an observed increase in serum total
      protein concentration at the 12th week of intervention. That the distribution of
      water may have changed was suggested by an increase in upper arm muscle
      circumference (UAMC). For low dose users, on the other hand, their body fat
      increased at wk8 as indicated by both BMI and skinfold thickness measurements,
      suggesting that supplement use gave a sense of false security. Apart from the
      change in serum total protein in the high dose group, no significant effect was
      observed on lipid, renal or electrolyte status, although fasting glucose rose
      within the normal range. This investigation demonstrated the importance of direct
      measures of body fatness, as opposed to those implied from weight-height
      relationships in the evaluation of management strategies for obesity. 

PMID- 24323172
TI  - Promotion of healing by orally administered glutamine in elemental diet after
      small intestinal injury by X-ray radiation.
AB  - Glutamine was administered orally to rats with damaged small intestinal mucosa as
      the result of injury by X-ray radiation at 10 Gy to the abdomen. The healing
      effects of glutamine on the injured mucosa were studied serially from the day of
      radiation (Day 0) to Day 4. The rats received two types of isocaloric elemental
      diet, Gln( + ) containing 2% glutamine and Gln( - ) containing no glutamine, by
      paired feeding. From Day 2 to Day 4, the wet weight, protein content, and DNA
      content of the jejunal mucosa were significantly greater in the Gln(+) than in
      the Gln(-) group. On Day 3, when the damage of the intestinal mucosa was the
      severest, the crypt cell production rate in the jejunum was significantly higher
      in the Gln(+) than in the Gln(-) group. The permeability of the intestinal mucosa
      to 51CrEDTA, administered to the rat stomach through an oro-gastric tube,
      remained significantly lower in the Gln( + ) group . Light microscopic findings
      showed that oedema in the lamina propria mucosae of jejunum and fusion of jejunal
      villi were milder in the Gln(+) group on Day 4. when the mucosal mass began to
      recover. The arterial and portal blood glutamine concentration, and glutamine
      extraction by the gut from arterial blood and phosphate-dependent glutaminase
      activity in the jejunal mucosa, were higher in the Gln(+) than in the Gln(--)
      group. Ornithine decarboxylase activity was increased in both the jejunum and the
      ileum from Day 3, but no difference was observed between the two groups. These
      findings suggest that, after X-ray radiation injury of the intestinal mucosa, the
      oral administration of the elemental diet containing 2% glutamine improved
      glutamine metabolism of the body, promoted the proliferation of jejunal
      epithelium, accelerated the recovery of the mucosal mass and the morphology of
      villi, and then contributed to maintaining the barrier function of the intestine
      from an early stage after the injury. 

PMID- 24323173
TI  - Options in obesity management.
AB  - The management of obesity requires acknowledgment of its heterogeneity. This
      derives from differences in pathogenesis, in genetic and psychological
      background. in physical activity. in food intake, and in aspects of lifestyle
      like cigarette smoking; as well as in degree, fat distribution. stability, and in
      consequences and associated disease. Pivotal to management is an appreciation
      that negative energy, balance can be achieved at various levels of energy intake.
      depending on physical activity or on the degree of inefficiency of energy
      utilization. Reduced food intake can help people start with reduction in body
      fatness and is sometimes necessary for extended periods. but in the long run, an
      emphasis on increased levels of physical activity is preferred. Management
      endpoints need careful consideration since a great deal can be done to help the
      obese without necessarily changing weight. It is important to document changes in
      body fat and its distribution particularly by way of abdominal girth. Setting
      other healthful endpoints. such as food intake itself, self-esteem, physical
      fitness, risk profile for non-communicable disease, and self-care, are equally
      important. Management options -- social, behavioural, exercise,
      pharmacotherapeutics and surgical - can be considered singly, sequentially or in
      combination. There are risks of management and these will include social,
      psychological (sense of failure and alteration in body image), economic
      nutritional and physical (eg injury), and the more specific side-effects of
      pharmacotherapeutics and of surgery. Finally, the prevention of obesity requires
      the early detection of risk, eg the emergence of abdominal fatness with little
      change in total body fatness, and attention to health education, regular physical
      activity and the use of food with little fat. 

PMID- 24323174
TI  - Consequences of electrical conductivity in an orb spider's capture web.
AB  - The glue-coated and wet capture spiral of the orb web of the garden cross spider
      Araneus diadematus is suspended between the dry silk radial and web frame
      threads. Here, we experimentally demonstrate that the capture spiral is
      electrically conductive because of necks of liquid connecting the droplets even
      if the thread is stretched. We examine how this conductivity of the capture
      spiral may lead to entrapment of charged airborne particles such as pollen, spray
      droplets and even insects. We further describe and model how the conducting
      spiral will also locally distort the Earth's ambient electric field. Finally, we
      examine the hypothesis that such distortion could be used by potential prey to
      detect the presence of a web but conclude that any effect would probably be too
      small to allow an insect to take evasive action. 

PMID- 24323175
TI  - Spatial separation from family in the mobile young of a biparental fish: risks
      and dynamics of returning home.
AB  - In species with extended parental care, mobile dependent young are potentially
      more vulnerable to predators when they stray and become separated from their
      parents. We would expect that the likelihood of, and latency time for, a
      separated young to safely return to its 'family unit' (i.e. parents and brood
      mates) to be, respectively, inversely and positively related to the initial
      distance of separation and potentially mediated by its age or body size. Using
      the biparental convict cichlid fish (Amatitlania siquia), we tested these
      predictions by capturing individual young and displacing them at varying
      distances from their family unit in both the field and laboratory. As expected,
      displaced fish were less likely, and took longer, to return to their family with
      increasing separation distance from the family unit. The body length of displaced
      young mediated these relationships and their antipredator behaviour; larger young
      refuged more than smaller ones and were also less likely to be eaten by
      predators. These results suggest that selection should favour strong affiliative
      behaviour in mobile young animals towards their brood mates and protective
      parents because straying from the family unit leads to increased exposure to
      predation and a reduced likelihood of returning home with increasing separation
      distance. 

PMID- 24323176
TI  - How flies respond to honey bee pheromone: the role of the foraging gene on
      reproductive response to queen mandibular pheromone.
AB  - In this study we test one central prediction from sociogenomic theory--that
      social and non-social taxa share common genetic toolkits that regulate
      reproduction in response to environmental cues. We exposed Drosophila females of
      rover (for(R)) and sitter (for(s)) genotypes to an ovary-suppressing pheromone
      derived from the honeybee Apis mellifera. Surprisingly, queen mandibular
      pheromone (QMP) affected several measures of fitness in flies, and in a manner
      comparable to the pheromone's normal effect on bee workers. QMP-treated sitter
      flies had smaller ovaries that contained fewer eggs than did untreated controls.
      QMP-treated rover flies, by contrast, showed a more variable pattern that only
      sometimes resulted in ovary inhibition, while a third strain of fly that contains
      a sitter mutant allele in a rover background (for(s2)) showed no ovarian response
      to QMP. Taken together, our results suggest that distinctly non-social insects
      have some capacity to respond to social cues, but that this response varies with
      fly genotype. In general, the interspecific response is consistent with a
      conserved gene set affecting reproductive physiology. The differential response
      among strains in particular suggests that for is itself important for modulating
      the fly's pheromonal response.

PMID- 24323177
TI  - Pre-transplant left ventricular diastolic dysfunction is associated with post
      transplant acute graft rejection and graft failure.
AB  - INTRODUCTION: Acute cellular rejection (ACR) is a significant cause of morbidity
      and graft failure in liver transplant recipients (LTR). Diastolic dysfunction
      (DD) is frequently present in patients with cirrhosis undergoing liver
      transplantation. However, it is unclear if DD leads to ACR. METHODS: Data was
      collected retrospectively for consecutive LTR between January 2000 and December
      2010. Demographic data and mortality related data was obtained from social
      security index. Primary outcome was biopsy proven ACR. Graft failure and all
      cause mortality were also evaluated. DD was evaluated as a predictor of these
      outcomes. Other echocardiographic indices were also assessed as predictors of ACR
      by using Cox proportional hazard modeling adjusted for covariates. RESULTS: A
      total of 970 LTR (mean age 53.2 +/- 10 years, women 34.6 % and white 64.5 %) were
      followed for 5.3 +/- 3.4 years. Patients with DD (n = 145, 14.9 %) were
      significantly more likely to develop ACRs (HR 10.56; 95 % CI 6.78-16.45, p value
      = 0.0001) as well as graft failure (HR 2.09; 95 % CI 1.22-3.59, p value = 0.007)
      and all-cause mortality (HR 1.52; 95 % CI 1.08-2.13, p = 0.01). There was an
      increase in the risk of these outcomes with worsening of DD, when adjusted for
      various risk factors such as donor and recipient age, gender, race, Framingham
      risk score, pre-transplant MELD, transplant etiology and cold ischemia time.
      CONCLUSION: Pre-transplant DD is significantly associated with increased risk of
      allograft rejection, graft failure and mortality. This signifies the importance
      of cardiac evaluation during the pre-transplant period.

PMID- 24323178
TI  - Preventing stricture formation by covered esophageal stent placement after
      endoscopic submucosal dissection for early esophageal cancer.
AB  - OBJECTIVE: We aimed to evaluate the efficacy and safety of fully covered
      esophageal stent placement for preventing esophageal strictures after endoscopic
      submucosal dissection (ESD). METHODS: Twenty-two patients with a mucosal defects
      that exceeded 75 % of the circumference of the esophagus after ESD treatment for
      superficial esophageal squamous cell carcinomas were grouped according to the
      type of mucosal defect and randomized to undergo fully covered esophageal stent
      placement post-ESD (group A, n = 11) or no stent placement (group B, n = 11). In
      group A, the esophageal stents were removed 8 weeks post-ESD. Endoscopy was
      performed when patients reported dysphagia symptoms and at 12 weeks post-ESD in
      patients without symptoms. Savary-Gilliard dilators were used for bougie dilation
      in patients experiencing esophageal stricture in both groups, and we compared the
      rates of post-ESD strictures and the need for bougie dilation procedures.
      RESULTS: The proportion of patients who developed a stricture was significantly
      lower in group A (18.2 %, n = 2) than in group B (72.7 %, n = 8) (P < 0.05).
      Moreover, the number of bougie dilation procedures was significantly lower in
      group A (mean 0.45, range 0-3) than in group B (mean 3.9, range 0-17) (P < 0.05).
      The two patients in group A who experienced stricture also had stent
      displacement. CONCLUSIONS: Esophageal stents are a safe and effective method of
      preventing esophageal strictures in cases where >75 % of the circumference of the
      esophagus has mucosal defects after ESD treatment for early esophageal cancer.

PMID- 24323179
TI  - The impact of alcohol consumption and cholecystectomy on small intestinal
      bacterial overgrowth.
AB  - BACKGROUND: The etiology of small intestinal bacterial overgrowth (SIBO) is
      diverse and frequently multi-factorial. SIBO is thought to result from structural
      changes of the gastrointestinal tract, disordered peristalsis of the stomach
      and/or small intestine, or a disruption of the normal mucosal defenses of the
      small intestine. Alcoholics are reported to have higher rates of SIBO, as
      diagnosed by jejunal aspirate; however, no data are available on the association
      between moderate alcohol consumption and SIBO. AIM: To evaluate the association
      between moderate alcohol consumption and SIBO and identify risk factors for SIBO
      using the lactulose breath test (LBT). METHODS: A retrospective chart review was
      completed for 210 consecutive patients who underwent the LBT between 2008 and
      2010. We reviewed demographic data, including age, race, body mass index, alcohol
      and tobacco history, medication use, comorbid medical conditions, and history of
      abdominal surgery. RESULTS: The study included 196 patients (68 % female; mean
      age 55 years), 93 of whom had a positive LBT (47.4 %). Of those patients who
      consumed a moderate amount of alcohol, 58 % had a positive LBT, compared to 38.9
      % of abstainers (P = 0.008). Those with a history of cholecystectomy had
      significantly lower rates of a positive LBT than those who had not (33.3 vs. 51.7
      % respectively; P = 0.031). Neither proton pump inhibitor (PPI) use nor tobacco
      use was associated with a positive LBT. CONCLUSION: In this retrospective review,
      moderate alcohol consumption was a strong risk factor for SIBO. Cholecystectomy
      appeared to be protective against SIBO. Neither PPI use nor tobacco use was
      associated with an increased risk of SIBO.

PMID- 24323181
TI  - Identifying cirrhosis patients for intensive disease management.

PMID- 24323180
TI  - Outcomes of computed tomography and magnetic resonance enterography in clinical
      practice of inflammatory bowel disease.
AB  - BACKGROUND: Computed tomography (CT) and magnetic resonance (MR) enterography are
      now widely used to diagnose and monitor Crohn's disease. AIM: We sought to assess
      the use of enterography for management of inflammatory bowel disease (IBD) in our
      medical center. METHODS: We performed a retrospective review of all patients
      diagnosed with IBD who underwent MR or CT enterography from November 1, 2010 to
      October 25, 2012 at our institution. We assessed disease complications identified
      by enterography, agreement between disease activity determined by endoscopy and
      enterography, association between inflammatory markers and enterography
      determined disease activity and recommended changes in medical and surgical
      management following enterography. RESULTS: A total of 311 enterography studies
      (291 MR and 20 CT enterographies) were performed on 270 patients, including 258
      (83.0 %) on patients with presumed Crohn's disease and 53 (17.0 %) with presumed
      ulcerative colitis. Active small bowel (SB) disease was noted in 73/311 (23.5 %)
      studies. Complications including strictures, perianal fistulas, abscesses and SB
      fistulas were noted in 108/311 (34.7 %) studies. Endoscopic and enterography
      defined active disease had an agreement of kappa = 0.36 in the ileum (n = 179). A
      total of 142/311 (45.7 %) enterographies were associated with recommended
      medication changes within 90 days while surgery or endoscopic dilation of
      stricture was recommended following 41/311 (13.2 %) enterographies. Enterography
      resulted in a change in diagnosis from ulcerative colitis to Crohn's in 5/311
      (1.6 %) studies. CONCLUSION: Enterography reveals active disease and
      complications not evident on endoscopy and should be considered in the initial
      diagnosis, assessment of disease activity, and monitoring of therapy in patients
      with IBD.

PMID- 24323182
TI  - Surveillance strategy for rectal neuroendocrine tumors according to recurrence
      risk stratification.
AB  - BACKGROUND/AIM: Rectal neuroendocrine tumors (NETs) have been increasing in
      incidence. However, the recommendations for disease surveillance after tumor
      resection have not been well established. We evaluated the long-term outcomes of
      rectal NETs and surveillance strategies according to recurrence risk
      stratification. METHODS: From January 2000 to July 2011, 188 patients diagnosed
      with rectal NETs were included in this study. Patient characteristics, treatment
      methods, recurrence rates, risk factors of recurrence, and surveillance schedules
      were analyzed. RESULTS: The male-to-female ratio was 1.29:1 and the mean age at
      diagnosis was 50.6 years. The mean tumor size was 6.5 (range 1-30) mm. A total of
      144 patients (76.6 %) were treated with endoscopic resection, and 44 patients
      (23.4 %) were treated with surgical resection as the initial treatment. During
      the follow-up period, ten patients (5.3 %) had disease recurrence, including one
      case of local recurrence and nine cases of recurrence at a distant site. Tumor
      size of >10 mm, invasion of the muscularis propria, increased mitotic index,
      lymphovascular invasion, and regional lymph node metastases were statistically
      significant predictors of recurrence by univariate analysis. Among the 152
      patients without risk factors of recurrence, only one patient who underwent
      transanal resection had a local recurrence at 15 months after surgery.
      CONCLUSION: Our patients with rectal NETs showed favorable clinical outcomes and
      had a low rate of recurrence. Intensive surveillance with endoscopy or imaging
      study may not be required in patients without risk factors for recurrence.

PMID- 24323183
TI  - Vegetarianism as a protective factor for colorectal adenoma and advanced adenoma
      in Asians.
AB  - BACKGROUND: Although epidemiologic and animal studies suggest a vegetarian diet
      protects against the development of colorectal cancer, the relationship between
      vegetarian diet and incidence of colorectal adenoma is not yet conclusive,
      especially for Asians. AIM: The purpose of this study was to examine the
      protective effect of a vegetarian diet against colorectal adenoma and advanced
      adenoma. METHODS: This cross-sectional study compared the prevalence of
      colorectal adenoma among Buddhist priests, who are obligatory vegetarians, with
      that among age and sex-matched controls. All the subjects underwent health
      checkups in a health-promotion center in Korea. RESULT: Colorectal adenoma and
      advanced adenoma were both more prevalent in the general population group than in
      the Buddhist priest group (25.2 vs. 17.9 %, 6.7 vs. 2.0 %). However, the
      prevalence of metabolic syndrome, high body mass index, and waist circumference
      were higher in the Buddhist priest group. According to univariate analysis, non
      vegetarian diet (general population) significantly increased the prevalence of
      colorectal adenoma and advanced adenoma compared with a vegetarian diet (Buddhist
      priests) (OR 1.54, 95 % CI 1.08-2.21, P = 0.018; OR 3.60, 95 % CI 1.53-8.48, P =
      0.003). In a conditional regression analysis model, non-vegetarian diet was also
      a significant risk factor for colorectal adenoma and advanced adenoma (OR 1.52,
      95 % CI 0.75-2.07, P = 0.043; OR 2.94, CI 0.97-7.18, P = 0.036). CONCLUSIONS:
      Vegetarianism may be effective in preventing both colorectal adenoma and advanced
      adenoma in Asians.

PMID- 24323184
TI  - Systemic evaluation of hypoxic-ischemic brain injury in neonatal rats.
AB  - The objective of the study was to evaluate the systematically rat model of
      neonatal hypoxic-ischemic brain damage. The right carotid arteries of 7-day-old
      healthy Wistar rats were ligated, and then, the rats were subjected to an
      environment with 8 % of oxygen. Four weeks after the birth, neurobehavioral test,
      water maze test, and motor-evoked potential and neuropathologic examinations were
      performed. The footprint analysis showed significantly larger and instable paces
      in the hypoxic-ischemic group (P < 0.05); the time that rats crossed the balance
      beam in the hypoxic-ischemic group was longer than the control group (P < 0.05).
      The water maze test showed that the escape latency of hypoxic-ischemic group was
      significantly longer than that of control group (P < 0.05). The hindlimb
      quadriceps compound muscle-evoked potential CMEP of rats in hypoxic-ischemic
      group showed that the wave amplitude was lower than that of control group (P <
      0.05). HE staining showed visible periventricular leukomalacia in hypoxic
      ischemic groups; disrupted nuclear membrane was detected in the IH group with
      transelectronmicroscopy; Immunohistochemistry: compared with control group, MBP
      positive neurocytes decreased, glial fibrillary acidic protein positive
      neurocytes increased in the periventricular zone (P < 0.05). Carotid artery
      ligation combining the hypoxic chamber created a reliable and stable rat model of
      neonatal hypoxic-ischemic brain damage and can be used for experimental research
      related to management of cerebral palsy.

PMID- 24323186
TI  - Proceedings of the 2nd translational preconditioning meeting Miami.

PMID- 24323187
TI  - Moving towards preconditioning for neurological disorders: are we ready for
      clinical trials?
AB  - The large volume of preclinical investigations begets the question of whether to
      proceed with clinical trials in preconditioning for neurological disorders,
      particularly for treatment of human cerebral ischemia. This important question
      was discussed during the 2nd Translational Preconditioning Meeting held at the
      University of Miami. While recommendations for proceeding to clinical trials have
      been devised in other fields of stroke therapy, such as neuroprotection, no such
      guidelines exist for preconditioning. During the discussion, the general opinion
      was to proceed with clinical preconditioning trials, with the understanding that
      initial trials be exploratory in nature and focus on the development of
      biomarkers, assessing the elicitability of the preconditioning response. 

PMID- 24323185
TI  - Observer agreement in pediatric semiquantitative vertebral fracture diagnosis.
AB  - BACKGROUND: The Genant semiquantitative (GSQ) method has been a standard
      procedure for diagnosis of vertebral fractures in adults but has only recently
      been shown to be of clinical utility in children. Observer agreement using the
      GSQ method in this age group has not been described. OBJECTIVE: To evaluate
      observer agreement on vertebral readability and vertebral fracture diagnosis
      using the GSQ method in pediatric vertebral morphometry. MATERIALS AND METHODS:
      Spine radiographs of 186 children with acute lymphoblastic leukemia were
      evaluated independently by three radiologists using the same GSQ methodology as
      in adults. A subset of 100 radiographs was evaluated on two occasions. RESULTS:
      An average of 4.7% of vertebrae were unreadable for the three radiologists.
      Intraobserver Cohen's kappa (kappa) on readability ranged from 0.434 to 0.648 at
      the vertebral level and from 0.416 to 0.611 at the patient level, while
      interobserver kappa for readability had a range of 0.330 to 0.504 at the
      vertebral level and 0.295 to 0.467 at the patient level. Intraobserver kappa for
      the presence of vertebral fracture had a range of 0.529 to 0.726 at the vertebral
      level and was 0.528 to 0.767 at the patient level. Interobserver kappa for
      fracture at the vertebral level ranged from 0.455 to 0.548 and from 0.433 to
      0.486 at the patient level. CONCLUSION: Most kappa values for both intra- and
      interobserver agreement in applying the GSQ method to pediatric spine radiographs
      were in the moderate to substantial range, comparable to the performance of the
      technique in adult studies. The GSQ method should be considered for use in
      pediatric research and clinical practice.

PMID- 24323188
TI  - Clinical application of preconditioning and postconditioning to achieve
      neuroprotection.
AB  - Ischemic conditioning is a form of endogenous protection induced by transient,
      subcritical ischemia in a tissue. Organs with high sensitivity to ischemia, such
      as the heart, the brain, and spinal cord, represent the most critical and
      potentially promising targets for potential therapeutic applications of ischemic
      conditioning. Numerous preclinical investigations have systematically studied the
      molecular pathways and potential benefits of both pre- and postconditioning with
      promising results. The purpose of this review is to summarize the present
      knowledge on cerebral pre- and postconditioning, with an emphasis in the clinical
      application of these forms of neuroprotection. A systematic MEDLINE search for
      the terms preconditioning and postconditioning was performed. Publications
      related to the nervous system and to human applications were selected and
      analyzed. Pre- and postconditioning appear to provide similar levels of
      neuroprotection. The preconditioning window of benefit can be subdivided into
      early and late effects, depending on whether the effect appears immediately after
      the sublethal stress or with a delay of days. In general, early effects have been
      associated posttranslational modification of critical proteins (membrane
      receptors, mitochondrial respiratory chain) while late effects are the result of
      gene up- or downregulation. Transient ischemic attacks appear to represent a form
      of clinically relevant preconditioning by inducing ischemic tolerance in the
      brain and reducing the severity of subsequent strokes. Remote forms of ischemic
      pre- and postconditioning have been more commonly used in clinical studies, as
      the remote application reduces the risk of injuring the target tissue for which
      protection is pursued. Limb transient ischemia is the preferred method of
      induction of remote conditioning with evidence supporting its safety. Clinical
      studies in a variety of populations at risk of central nervous damage including
      carotid disease, cervical myelopathy, and subarachnoid hemorrhage have shown
      improvement in surrogate markers of injury. Promising preclinical and early
      clinical studies noting improvement in surrogate markers of central nervous
      injury after the use of remote pre- and postconditioning treatments demand follow
      up systematic investigations to address effectiveness. Challenges in the
      application of these techniques to pressing clinical cerebrovascular disease
      ought to be overcome through careful, well-designed, translational
      investigations. 

PMID- 24323189
TI  - Preconditioning for traumatic brain injury.
AB  - Traumatic brain injury (TBI) treatment is now focused on the prevention of
      primary injury and reduction of secondary injury. However, no single effective
      treatment is available as yet for the mitigation of traumatic brain damage in
      humans. Both chemical and environmental stresses applied before injury have been
      shown to induce consequent protection against post-TBI neuronal death. This
      concept termed "preconditioning" is achieved by exposure to different pre-injury
      stressors to achieve the induction of "tolerance" to the effect of the TBI.
      However, the precise mechanisms underlying this "tolerance" phenomenon are not
      fully understood in TBI, and therefore even less information is available about
      possible indications in clinical TBI patients. In this review, we will summarize
      TBI pathophysiology, and discuss existing animal studies demonstrating the
      efficacy of preconditioning in diffuse and focal type of TBI. We will also review
      other non-TBI preconditioning studies, including ischemic, environmental, and
      chemical preconditioning, which maybe relevant to TBI. To date, no clinical
      studies exist in this field, and we speculate on possible future clinical
      situations, in which pre-TBI preconditioning could be considered. 

PMID- 24323190
TI  - Epigenetics and the environment: in search of the "toleroasome" vital to
      execution of ischemic preconditioning.
AB  - Activation and repression of gene expression are key features of ischemic
      tolerance. Converging lines of inquiry from several groups suggests that
      epigenetic proteins may transduce sublethal stresses, including bioenergetic or
      oxidative stress into durable (2-3 days) changes in gene expression that mediate
      ischemic tolerance. Here we discuss the potential mechanisms by which changes in
      cell state (e.g., ATP, NAD+, and oxygen) can modify specific targets including
      polycomb complexes, jumonji domain histone demethylases, and zinc and NAD
      dependent histone decetylases and thus trigger an adaptive program. A major
      unanswered question is whether these proteins work in parallel or convergently as
      part of a "tolerosome" (tolero is the Latin word for tolerance), a multiprotein
      complex recruited to promoters or enhancers of specific genes, to mediate
      preconditioning. Whatever the case may be, epigenetic proteins are fertile
      targets for the treatment of stroke.

PMID- 24323191
TI  - Poised for success: implementation of sound conditioning strategies to promote
      endogenous protective responses to stroke in patients.
AB  - The following perspective represents our summary of questions, ideas, concerns,
      and recommendations expressed by speakers and discussants at the second Biennial
      Translational Preconditioning Workshop held in Miami in December 2011. 

PMID- 24323192
TI  - Optical glucose analogs of aminolevulinic acid for fluorescence-guided tumor
      resection and photodynamic therapy.
AB  - PURPOSE: We have developed and tested a novel conjugation of the clinically used
      prodrug aminolevulinic acid with 2-deoxyglucosamine as a novel probe (ALA-2DG)
      for fluorescence imaging and photodynamic therapy. PROCEDURES: ALA-2DG was
      successfully synthesized, and the mechanisms of probe uptake, PpIX synthesis, and
      photodynamic therapy efficacy were evaluated in vitro and in vivo. RESULTS: ALA
      2DG led to PpIX synthesis in tumor cells in vitro and in tumor in vivo.
      Competitive and inhibitory assays in vitro showed a reduction of this PpIX
      synthesis that was not observed when cells were incubated with ALA itself,
      indicating that intracellular uptake of ALA-2DG occurs by GLUT-mediated active
      transport. Initial photodynamic therapy studies confirmed the efficacy of ALA-2DG
      as a photodynamic sensitizer. CONCLUSIONS: The in vitro assays suggest that ALA
      2DG is taken up by cells via glucose transporters. Initial studies in oral cancer
      demonstrated the applicability of ALA-2DG for in vivo imaging and its potential
      as an alternative to ALA-PpIX-based fluorescence diagnostics and photodynamic
      therapy, providing higher tumor specificity.

PMID- 24323193
TI  - Cloning and expression patterns of the brine shrimp (Artemia sinica) glycogen
      phosphorylase (GPase) gene during development and in response to temperature
      stress.
AB  - Glycogen serves as a metabolic reserve and is involved in macromolecular
      synthesis. Glycogen phosphorylase (GPase) is a key enzyme involved in
      intracellular glycogen catabolism, catalyzing the first step in glycogen
      degradation. In the diapause, GPase catalyzes glycogen into the closely related
      molecule, sorbitol. In this study, the full-length cDNA of the GPase gene (2,790
      bp) was isolated from Artemia sinica for the first time by rapid amplification of
      cDNA ends technology. The GPase gene encoded a protein of 853 amino acids
      belonging to the Glycosyltransferase GTB type superfamily. The expression pattern
      and location of GPase were investigated at various stages during the embryonic
      development of A. sinica using real-time PCR and in situ hybridization. High
      GPase expression was detected at the 0 and 5 h stages. Subsequently, expression
      declined and was maintained at a low level during the stages from 10 to 40 h
      following by a small increase at day 3. Expression was downregulated at
      temperatures ranging from 25 to 20  degrees C and was subsequently upregulated in
      the range 15-5  degrees C. In situ hybridization assays showed wide distribution
      of the GPase gene during different developmental stages. From the results of this
      study, we conclude that the GPase gene expression is stress-related and might
      play an important role in Artemia development and metabolism.

PMID- 24323194
TI  - Functional study on the mutations in the silkworm (Bombyx mori)
      acetylcholinesterase type 1 gene (ace1) and its recombinant proteins.
AB  - The acetylcholinesterase of Lepidoptera insects is encoded by two genes, ace1 and
      ace2. The expression of the ace1 gene is significantly higher than that of the
      ace2 gene, and mutations in ace1 are one of the major reasons for pesticide
      resistance in insects. In order to investigate the effects of the mutations in
      ace1's characteristic sites on pesticide resistance, we generated mutations for
      three amino acids using site-directed mutagenesis, which were
      Ala(GCG)303Ser(TCG), Gly(GGA)329Ala(GCA) and Leu (TCT)554Ser(TTC). The
      Baculovirus expression system was used for the eukaryotic expression of the wild
      type ace1 (wace1) and the mutant ace1 (mace1). SDS-PAGE and Western blotting were
      used to detect the targeting proteins with expected sizeof about 76 kDa. The
      expression products were purified for the determination of AChE activity and the
      inhibitory effects of physostigmine and phoxim. We observed no significant
      differences in the overall activity of the wild type and mutant AChEs. However,
      with 10 min of physostigmine (10 MUM) inhibition, the remaining activity of the
      wild type AChE was significantly lower than that of the mutant AChE. Ten min
      inhibition with 33.4 MUM phoxim also resulted in significantly lower remaining
      activity of the wild type AChE than that of the mutant AChE. These results
      indicated that mutations for the three amino acids reduced the sensitivity of
      AChE to physostigmine and phoxim, which laid the foundation for future in vivo
      studies on AChE's roles in pesticide resistance.

PMID- 24323195
TI  - BcMF21 is important for pollen development and germination in Brassica campestris
      ssp. chinensis.
AB  - Brassica campestris Male Fertility 21 (BcMF21) was previously isolated from the
      flower buds of Chinese cabbage (Brassica campestris L. ssp. chinensis Makino,
      syn. B. rapa ssp. chinensis) and expressed specifically in tapetum and
      microspores during the meiosis stage and the uninucleate stage of microspore
      development. Here, we used antisense RNA technology to knock down the expression
      level of BcMF21 in B. campestris and analyzed the phenotype of the transgenic
      plants. Alexander staining and scanning electron microscope revealed sterility
      and exine deformities in the mature pollen grains of BcMF21 antisense RNA
      transgenic plants. The germination furrow of the BcMF21 antisense RNA transgenic
      pollen was covered by lipid like materials. The pollen tubes burst and could not
      grow normally in vitro. Therefore, we presented here BcMF21 might be an important
      gene for pollen development and germination.

PMID- 24323196
TI  - Is the US "leading from behind" on health policy?

PMID- 24323197
TI  - [Mindfulness, cognitive function and 'successful ageing'].
AB  - There is ample empirical evidence that cultivation of mindfulness in dedicated
      target populations has positive health effects, specifically in the context of
      stress management and mental disorders. Research into the effectiveness of
      mindfulness-based interventions (MBI) in age-related conditions and disorders is
      still in its infancy. This paper describes, in brief, the scientific background
      of MBI and its potential to contribute to successful ageing and the care for and
      wellbeing of older people. Special focus is dedicated to the contribution of
      optimal cognitive abilities to this success and to what extent MBI may support
      cognitive reserve.

PMID- 24323198
TI  - Sleep EEG composition in the first three months of life in monozygotic and
      dizygotic twins.
AB  - We investigated genetic influence on sleep electroencephalogram (EEG) composition
      by a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins in the
      first 3 months of life. Polysomnographic (PSG) recordings were obtained in 10 MZ
      and 20 DZ twin pairs in the 37th, 46th, and 52nd week of postmenstrual age (PMA).
      The EEG power spectra were generated on the basis of fast Fourier transformation
      (FFT). Genetic influence on active sleep/rapid eye movement (AS/REM)] and quiet
      sleep/non rapid eye movement (QS/NREM) sleep composition was estimated by
      calculating within pair concordance and the intraclass correlation coefficients
      (ICCs) for delta (0.5-3.5 Hz), theta (4-7.5 Hz), alpha (8-11.5 Hz), sigma (12-14
      Hz), and beta (14.5-20 Hz) at central derivation. MZ twins show higher ICCs than
      DZ twins for alpha, sigma, and beta spectral powers during QS/NREM sleep in the
      37th, 46th, and 52nd week PMA. However, there was no significant difference (P >
      .05) between the 2 types of twins in absolute differences of EEG spectral power
      of the alpha, beta, and sigma frequency ranges in the 37th, 46th, and 52nd week
      PMA. The greatest mean absolute difference within MZ and DZ twin pairs and also
      between MZ and DZ twin groups was identified in the delta frequency range. Our
      findings gave an indication of genetic influence on alpha, sigma, and beta
      frequency ranges in the QS/NREM sleep stage.

PMID- 24323199
TI  - Prescription drug abuse: executive summary of a policy position paper from the
      American College of Physicians.

PMID- 24323201
TI  - Differences in depressive symptoms between Korean and American outpatients with
      major depressive disorder.
AB  - Previous epidemiologic studies have revealed that East-Asian populations
      experience fewer depressive symptoms than American populations do. However, it is
      unclear whether this difference applies to clinical patients with major
      depressive disorder (MDD). This present study included 1592 Korean and 3744
      American outpatients who were 18 years of age or older and met the Diagnostic and
      Statistical Manual of Mental Disorders, 4th ed. criteria for single or recurrent
      episodes of nonpsychotic MDD, and evaluated their symptoms of depression using
      the Hamilton Depression Rating Scale and the Quality of Life Enjoyment and
      Satisfaction Questionnaire Short Form. Korean patients scored significantly lower
      for guilt and depressed mood items, and higher for hypochondriasis and
      suicidality items than American patients did, after adjusting for total Hamilton
      Depression Rating Scale scores. Conversely, no significant differences were found
      in quality and function of daily life between groups. Multivariate logistic
      regression analyses revealed that Korean patients experienced less frequent
      depressed mood and guilt, including verbal and nonverbal expression of depressed
      mood [adjusted odds ratio (AOR) = 0.14, 95% confidence interval (CI) 0.08-0.23]
      and feelings of punishment (AOR = 0.036, 95% CI 0.025-0.054) when compared with
      Americans after adjusting for age and sex. Conversely, Korean patients
      experienced more frequent suicidality and hypochondriasis, including suicidal
      ideas or gestures (AOR = 2.10, 95% CI 1.60-2.76) and self-absorption of
      hypochondriasis (AOR = 1.94, 95% CI 1.70-2.20). In conclusion, decreased
      expression of depressed mood and guilt may cause underdiagnosis of MDD in Korean
      patients. Early diagnosis of and intervention for depression and suicide may be
      delayed because of this specific cross-cultural difference in depression
      symptoms.

PMID- 24323200
TI  - Socioeconomic factors influencing antipsychotic prescription for schizophrenia
      inpatients in China: a cross-sectional study.
AB  - Medication is critical in schizophrenia therapy, and prescription patterns have
      changed considerably over the past 20 years in China. This study attempts to
      evaluate the prescription patterns of antipsychotics for inpatients with
      schizophrenia in China and to identify factors influencing these patterns. Claims
      data of inpatients diagnosed with schizophrenia in 2010 were derived from the
      reimbursement database of Wuhan and Wuxi. A total of 5251 inpatients received
      antipsychotic medications, of whom 29.0% received second-generation
      antipsychotics apart from clozapine (SGAs#), 13.7% received clozapine (CLO),
      13.5% received first-generation antipsychotics (FGAs), 43.8% received at least
      both drug classes, and 5.1% used FGAs, CLO as well as SGAs#. Multinomial logistic
      regression for 2904 identified inpatients showed that factors of drug
      reimbursement policy, duration of hospitalization, age group, and municipality
      were statistically significant in antipsychotic medication. Drug list B and the
      25-45 age group presented a significant relationship with SGAs# prescription
      (FGAs vs. SGAs#). Furthermore, the 12-30-day duration of hospitalization and the
      25-45 age group showed a significant relationship with SGAs# prescription (CLO
      vs. SGAs#). Socioeconomic factors such as health insurance policies, especially
      reimbursement policy of drugs and payment system, as well as mental health
      resource distribution are important in antipsychotic prescription in China.

PMID- 24323202
TI  - WO3-alpha-Fe2O3 composite photoelectrodes with low onset potential for solar
      water oxidation.
AB  - The physical and photoelectrochemical properties of a composite oxide
      photoelectrode comprised of alpha-Fe2O3 and WO3 crystals is investigated. The
      composite films exhibit a water oxidation photocurrent onset potential as low as
      0.43 V vs. RHE, a value considerably lower than that of pure alpha-Fe2O3
      photoanodes prepared in comparable synthesis conditions. This result represents
      one of the lowest onset potentials measured for hematite-based PEC water
      oxidation systems. Compositional analysis by X-ray Photoelectron Spectroscopy and
      Energy Dispersive Spectroscopy indicates the composition of the films differs
      between the surfaces and bulk, with tungsten found to be concentrated in the
      surface region. Post-reaction Raman spectroscopy characterization demonstrates
      that water interacts with surface WO3 crystals, an event that is associated with
      the formation of a hydrated form of the oxide. 

PMID- 24323203
TI  - Image reconstruction of fluorescent molecular tomography based on the simplified
      matrix system.
AB  - Fluorescent molecular tomographic image reconstruction usually involves
      repeatedly solving large-scale matrix equations, which are computationally
      expensive. In this paper, a method is proposed to reduce the scale of the matrix
      system. The Jacobian matrix is simplified by deleting the columns or the rows
      whose values are smaller than a threshold. Furthermore, the measurement data are
      divided into two groups and are used for iteration of image reconstruction in
      turn. The simplified system is then solved in the wavelet domain to further
      accelerate the process of solving the inverse problem. Simulation results
      demonstrate that the proposed method can significantly speed up the
      reconstruction process. 

PMID- 24323204
TI  - Engineering parabolic beams with dynamic intensity profiles.
AB  - We present optical fields formed by superposing nondiffracting parabolic beams
      with distinct longitudinal wave-vector components, generating light profiles that
      display intensity fluxes following parabolic paths in the transverse plane. Their
      propagation dynamics vary depending on the physical mechanism originating
      interference, where the possibilities include constructive and destructive
      interference between traveling parabolic beams, interference between stationary
      parabolic modes, and combinations of these. The dark parabolic region exhibited
      by parabolic beams permits a straightforward superposition of intensity fluxes,
      allowing formation of a variety of profiles, which can exhibit circular,
      elliptic, and other symmetries. 

PMID- 24323205
TI  - Online tracking of deformable objects under occlusion using dominant points.
AB  - This paper deals with tracking of deformable objects in the presence of occlusion
      using dominant point representation of the boundary contour. A novel nonintegral
      time propagation model for propagating the dominant points is proposed. It uses
      an initial guess generated from a linear operation and an analytical conjugate
      gradient approach for online robust learning of the shape deformation and motion
      model. A scheme is presented to automatically detect and correct the region of
      large local deformation. In order to deal with occlusion, admissible restrictions
      on deformation and motion of the object are automatically determined. The
      proposed method overcomes the need of offline learning and learns the deformation
      and motion model of the object using very few initial frames of the input video.
      The performance of the method is demonstrated using varieties of videos of
      different objects. 

PMID- 24323206
TI  - Moving target detection in thermal infrared imagery using spatiotemporal
      information.
AB  - An efficient target detection algorithm for detecting moving targets in infrared
      imagery using spatiotemporal information is presented. The output of the spatial
      processing serves as input to the temporal stage in a layered manner. The spatial
      information is obtained using joint space-spatial-frequency distribution and
      Renyi entropy. Temporal information is incorporated using background subtraction.
      By utilizing both spatial and temporal information, it is observed that the
      proposed method can achieve both high detection and a low false-alarm rate. The
      method is validated with experimentally generated data consisting of a variety of
      moving targets. Experimental results demonstrate a high value of F-measure for
      the proposed algorithm. 

PMID- 24323207
TI  - Analysis and design of hybrid ARROW-B plasmonic waveguides.
AB  - A hybrid antiresonant reflecting waveguide, type B (ARROW-B) plasmonic waveguide
      based on the resonant coupling between a guided dielectric mode and surface
      plasmon polariton wave is proposed. Employing the finite element method, hybrid
      modes including two bound supermodes are obtained at visible frequencies by
      varying the environmental refractive index. We investigate the propagation
      characteristics of hybrid modes, where the significant change of modal power by
      the symmetric bound mode is observed in plasmonic waveguide coupling suitable for
      highly sensitive detection of bulk refractive index change. Further, anomalous
      dispersion is shown by the antisymmetric bound mode which leads to large group
      velocity dispersion of -3.165*10(4) ps/km nm and, thus, makes this hybrid
      plasmonic waveguide ideal for observation of soliton generation.

PMID- 24323208
TI  - Comparison of the performance of inverse transformation methods from OSA-UCS to
      CIEXYZ.
AB  - The Optical Society of America's Uniform Color Scales (OSA-UCS) is one of the
      color spaces that most closely approximate a "true" uniform color space.
      Different techniques have been used to convert OSA-UCS-based color specification
      parameters, L, j, and g, to the CIE tristimulus values, X, Y, and Z. However,
      none of these methods provides a direct method of inverting OSA-UCS to CIEXYZ
      values. Thus, numerical algorithms, such as the Newton-Raphson method, have been
      employed to obtain the transformations. The relative low accuracy and long
      computation time of this method makes it undesirable for practical applications.
      An artificial neural network (ANN) was employed to convert OSA-UCS to CIEXYZ. Its
      performance was compared with that of numerical methods. After optimization, ANN
      gave a better performance with a mean error (DeltaEXYZ) of 1.0*10(-4) and a
      conversion time of less than 1 s for 1891 samples.

PMID- 24323209
TI  - Nonquadratic penalization improves near-infrared diffuse optical tomography.
AB  - A new approach that can easily incorporate any generic penalty function into the
      diffuse optical tomographic image reconstruction is introduced to show the
      utility of nonquadratic penalty functions. The penalty functions that were used
      include quadratic (l2), absolute (l1), Cauchy, and Geman-McClure. The
      regularization parameter in each of these cases was obtained automatically by
      using the generalized cross-validation method. The reconstruction results were
      systematically compared with each other via utilization of quantitative metrics,
      such as relative error and Pearson correlation. The reconstruction results
      indicate that, while the quadratic penalty may be able to provide better
      separation between two closely spaced targets, its contrast recovery capability
      is limited, and the sparseness promoting penalties, such as l1, Cauchy, and Geman
      McClure have better utility in reconstructing high-contrast and complex-shaped
      targets, with the Geman-McClure penalty being the most optimal one.

PMID- 24323210
TI  - Unified multiframe super-resolution of matte, foreground, and background.
AB  - Reconstruction of a super-resolved image from multiple frames and extraction of
      matte are two popular topics that have been solved independently. In this paper,
      we advocate a unified framework that assimilates matting within the super
      resolution model. We show that joint estimation is advantageous, as super
      resolved edge information helps in obtaining a sharp matte, while the matte in
      turn aids in resolving fine details. We propose a multiframe approach to increase
      the spatial resolution of the matte, foreground, and background. This is
      validated extensively on examples from standard matting datasets. 

PMID- 24323211
TI  - Theoretical analysis and experimental verification of six-step spatial phase
      shifting shearing interferometry by double gratings.
AB  - In order to measure the phase projection in moire tomography, in this paper we
      present a new spatial phase-shifting shearing interferometry that consists only
      of a crossed grating and a linear grating. With it, six phase-shifted
      interferograms can be acquired simultaneously. The intensity distributions of
      these six interferograms are derived based on the scalar diffraction theory.
      Analytical results indicate that phase shifts are symmetrically and consistently
      distributed in the vertical and horizontal directions. Moreover, phase-shift
      values depend primarily on the parameters of the optical structure. And a six
      step phase-shifting algorithm with arbitrary phase-shift values in two
      perpendicular directions is proposed to extract the phase information. The phase
      retrieval results of the spherical wave have verified the validity of the
      proposed method. Finally, an experiment with a plane incident wave is performed
      to measure the first-order derivative of the phase projection of a propane flame.

PMID- 24323212
TI  - Secondary source of quantum or classical partially polarized states.
AB  - A simple device is presented that serves as a secondary source of light with
      prescribed polarization properties. The technique employed is based on the
      Schmidt purification of a mixed quantum state. Such a purification can be applied
      to quantum and to classical polarization states. The device presented here can be
      used with both classical and quantum primary sources of light. It allows
      controlling the degree of polarization as well as the Stokes vector that enters
      the decomposition of a light beam in a fully unpolarized and a fully polarized
      component. 

PMID- 24323213
TI  - Scattering of a Gaussian beam by an elliptical cylinder using the vectorial
      complex ray model.
AB  - The scattered waves of a shaped beam by an infinite cylinder in the far field
      are, stricto sensu, neither cylindrical nor spherical, so the asymptotic form of
      special functions involved in the theories based on the rigorous solution of
      Maxwell equations cannot be used to evaluate scattered intensities, even in the
      most simple case of Gaussian beam scattering by an infinite circular cylinder.
      Thus, although theories exist for the scattering of a shaped beam by infinite
      cylinders with circular and elliptical sections, the numerical calculations are
      limited to the near field. The vectorial complex ray model (VCRM) developed by
      Ren et al. describes waves by rays with a new property: the curvature of the
      wavefront. It is suitable to deal with the scattering of an arbitrarily shaped
      beam by a particle with a smooth surface of any form. In this paper, we apply
      this method to the scattering of an infinite elliptical cylinder illuminated by a
      Gaussian beam at normal incidence with an arbitrary position and orientation
      relative to the symmetric axis of the elliptical section of the cylinder. The
      method for calculating the curvature of an arbitrary surface is given and applied
      in the determination of the two curvature radii of the Gaussian beam wavefront at
      any point. Scattered intensities for different parameters of the beam and the
      particle as well as observation distance are presented to reveal the scattering
      properties and new phenomena observed in the beam scattering by an infinite
      elliptical cylinder.

PMID- 24323214
TI  - Study on low-phase-noise optoelectronic oscillator and high-sensitivity phase
      noise measurement system.
AB  - An analytic model for an injection-locked dual-loop optoelectronic oscillator
      (OEO) is proposed and verified by experiments in this paper. Based on this
      theoretical model, the effect of injection power on the single-sideband phase
      noise of the OEO is analyzed, and results suggest that moderate injection is one
      key factor for a balance between phase noise and spur for OEO. In order to
      measure superlow phase noise of OEOs, a cross-correlation measurement system
      based on the fiber delay line is built, in which high linear photodetector and
      low-phase-noise amplifier are used to improve systematic sensitivity. The cross
      correlation measurement system is validated by experiments, and its noise floor
      for the X band is about -130 dBc/Hz at 1 kHz and -168 dBc/Hz at 10 kHz after a
      cross correlation of 200 times.

PMID- 24323215
TI  - Optimization for nonmagnetic concentrator with minimized scattering.
AB  - Based on the generalized transformation for a nonmagnetic cylindrical
      concentrator, we present nonlinear coordinate transformations to realize
      excellent concentrating performance with minimized scattering. By matching the
      impedance at both the inner and outer boundaries and utilizing nonlinear
      optimization techniques, the best parameters of the nonlinear transformation can
      be determined. Results show that the concentrating power is sensitive to the
      impedance at the inner interface. In addition, an alternating layered system
      consisting of nonmagnetic isotropic materials is applied to experimentally mimic
      the concentrator, and excellent concentrating performances have been observed. 

PMID- 24323216
TI  - A unified account of gloss and lightness perception in terms of gamut relativity.
AB  - A recently introduced computational theory of visual surface representation,
      termed gamut relativity, overturns the classical assumption that brightness,
      lightness, and transparency constitute perceptual dimensions corresponding to the
      physical dimensions of luminance, diffuse reflectance, and transmittance,
      respectively. Here I extend the theory to show how surface gloss and lightness
      can be understood in a unified manner in terms of the vector computation of
      "layered representations" of surface and illumination properties, rather than as
      perceptual dimensions corresponding to diffuse and specular reflectance,
      respectively. The theory simulates the effects of image histogram skewness on
      surface gloss/lightness and lightness constancy as a function of specular
      highlight intensity. More generally, gamut relativity clarifies, unifies, and
      generalizes a wide body of previous theoretical and experimental work aimed at
      understanding how the visual system parses the retinal image into layered
      representations of surface and illumination properties. 

PMID- 24323217
TI  - Texture classification using discrete Tchebichef moments.
AB  - In this paper, a method to characterize texture images based on discrete
      Tchebichef moments is presented. A global signature vector is derived from the
      moment matrix by taking into account both the magnitudes of the moments and their
      order. The performance of our method in several texture classification problems
      was compared with that achieved through other standard approaches. These include
      Haralick's gray-level co-occurrence matrices, Gabor filters, and local binary
      patterns. An extensive texture classification study was carried out by selecting
      images with different contents from the Brodatz, Outex, and VisTex databases. The
      results show that the proposed method is able to capture the essential
      information about texture, showing comparable or even higher performance than
      conventional procedures. Thus, it can be considered as an effective and
      competitive technique for texture characterization. 

PMID- 24323218
TI  - Iterative, backscatter-analysis algorithms for increasing transmission and
      focusing light through highly scattering random media.
AB  - Scattering hinders the passage of light through random media and consequently
      limits the usefulness of optical techniques for sensing and imaging. Thus,
      methods for increasing the transmission of light through such random media are of
      interest. Against this backdrop, recent theoretical and experimental advances
      have suggested the existence of a few highly transmitting eigen-wavefronts with
      transmission coefficients close to 1 in strongly backscattering random media.
      Here, we numerically analyze this phenomenon in 2D with fully spectrally accurate
      simulators and provide rigorous numerical evidence confirming the existence of
      these highly transmitting eigen-wavefronts in random media with periodic boundary
      conditions that are composed of hundreds of thousands of nonabsorbing scatterers.
      Motivated by bio-imaging applications in which it is not possible to measure the
      transmitted fields, we develop physically realizable algorithms for increasing
      the transmission through such random media using backscatter analysis. We show
      via numerical simulations that the algorithms converge rapidly, yielding a near
      optimum wavefront in just a few iterations. We also develop an algorithm that
      combines the knowledge of these highly transmitting eigen-wavefronts obtained
      from backscatter analysis with intensity measurements at a point to produce a
      near-optimal focus with significantly fewer measurements than a method that does
      not utilize this information. 

PMID- 24323219
TI  - Metamaterial apertures for coherent computational imaging on the physical layer.
AB  - We introduce the concept of a metamaterial aperture, in which an underlying
      reference mode interacts with a designed metamaterial surface to produce a series
      of complex field patterns. The resonant frequencies of the metamaterial elements
      are randomly distributed over a large bandwidth (18-26 GHz), such that the
      aperture produces a rapidly varying sequence of field patterns as a function of
      the input frequency. As the frequency of operation is scanned, different subsets
      of metamaterial elements become active, in turn varying the field patterns at the
      scene. Scene information can thus be indexed by frequency, with the overall
      effectiveness of the imaging scheme tied to the diversity of the generated field
      patterns. As the quality (Q-) factor of the metamaterial resonators increases,
      the number of distinct field patterns that can be generated increases-improving
      scene estimation. In this work we provide the foundation for computational
      imaging with metamaterial apertures based on frequency diversity, and establish
      that for resonators with physically relevant Q-factors, there are potentially
      enough distinct measurements of a typical scene within a reasonable bandwidth to
      achieve diffraction-limited reconstructions of physical scenes.

PMID- 24323220
TI  - Methodology to optimize detector geometry in fluorescence tomography of tissue
      using the minimized curvature of the summed diffuse sensitivity projections.
AB  - The dependence of the sensitivity function in fluorescence tomography on the
      geometry of the excitation source and detection locations can severely influence
      an imaging system's ability to recover fluorescent distributions. Here a
      methodology for choosing imaging configuration based on the uniformity of the
      sensitivity function is presented. The uniformity of detection sensitivity is
      correlated with reconstruction accuracy in silico, and reconstructions in a
      murine head model show that a detector configuration optimized using Nelder-Mead
      minimization improves recovery over uniformly sampled tomography. 

PMID- 24323221
TI  - Temporal spreading generated by diffraction in the focusing of ultrashort light
      pulses with perfectly conducting spherical mirrors.
AB  - We study femtosecond pulses at the focal plane of a perfectly conducting
      spherical mirror which is a dispersionless system, that is, it introduces no
      group velocity dispersion and no propagation time difference to the pulses after
      reflection. By using the scalar diffraction theory we will show that the
      neglected terms in the diffraction integral, when using the approximation of the
      bandwidth being smaller than the frequency of the carrier, have a significant
      influence on imaging if a laser pulse of a few femtoseconds is used in time
      resolved imaging. The neglected terms introduce temporal spreading to extremely
      short pulses of a few optical cycles incident on the mirror, which avoids a fully
      compensated pulse, i.e., a one optical cycle pulse, at the focus of the mirror.
      The study in this paper also applies to refracting optical systems such as
      microscope objectives or lenses. 

PMID- 24323222
TI  - Formation of circular fringes by interference of two boundary diffraction waves
      using holography.
AB  - The theory of boundary diffraction waves (BDWs) is gaining importance due to its
      simplicity and physically appealing nature. The present work reports formation of
      circular fringes far away from the geometrically illuminated region by
      interference of two BDWs. One BDW is reconstructed from the hologram while the
      second is coming directly from the knife-edge. The uniqueness of the fringes is
      that their position can be controlled on the screen at will and fringes can be
      produced with bright as well as dark central fringe. These results could play an
      important role in understanding the nature of diffraction of light. 

PMID- 24323223
TI  - Through-wall electromagnetic scattering by N conducting cylinders.
AB  - A spectral-domain analysis is presented for the scattering by perfectly
      conducting cylindrical objects behind a dielectric wall. The solution is
      developed with an analytical-numerical technique, based on the cylindrical wave
      approach. Suitable cylindrical functions and their spectral representations are
      introduced as basis functions for the scattered fields, to deal with their
      interaction with the planar interfaces bounding the wall. The numerical solution
      is given in TE and TM polarizations states, and in both near- and far-field
      zones. The model yields an accurate computation of direct scattering that can be
      useful for through-wall-imaging applications. A stack of three different
      dielectric media is considered in the theoretical model. In the numerical
      results, the upper medium, where the incident field is generated, is assumed to
      be filled by air, the central layer represents the wall, and the lower medium,
      which contains the scatterers, is air filled, too. Also general problems of
      scattering by buried objects can be simulated, being the cylinders buried in a
      medium of arbitrary permittivity, placed below a dielectric layer. 

PMID- 24323224
TI  - Analytical description of high-aperture STED resolution with 0-2pi vortex phase
      modulation.
AB  - Stimulated emission depletion (STED) can achieve optical superresolution, with
      the optical diffraction limit broken by the suppression on the periphery of the
      fluorescent focal spot. Previously, it is generally experimentally accepted that
      there exists an inverse square root relationship with the STED power and the
      resolution, but with arbitrary coefficients in expression. In this paper, we have
      removed the arbitrary coefficients by exploring the relationship between the STED
      power and the achievable resolution from vector optical theory for the widely
      used 0-2pi vortex phase modulation. Electromagnetic fields of the focal region of
      a high numerical aperture objective are calculated and approximated into
      polynomials of radius in the focal plane, and analytical expression of resolution
      as a function of the STED intensity has been derived. As a result, the resolution
      can be estimated directly from the measurement of the saturation power of the dye
      and the STED power applied in the region of high STED power. 

PMID- 24323225
TI  - Electric and magnetic polarization singularities of first-order Laguerre-Gaussian
      beams diffracted at a half-plane screen.
AB  - Based on the vector Fresnel diffraction integrals, analytical expressions for the
      electric and magnetic components of first-order Laguerre-Gaussian beams
      diffracted at a half-plane screen are derived and used to study the electric and
      magnetic polarization singularities in the diffraction field for both two- and
      three-dimensional (2D and 3D) cases. It is shown that there exist 2D and 3D
      electric and magnetic polarization singularities in the diffraction field, which
      do not coincide each other in general. By suitably varying the waist width ratio,
      off-axis displacement parameter, amplitude ratio, or propagation distance, the
      motion, pair-creation, and annihilation of circular polarization singularities,
      and the motion of linear polarization singularities take place in 2D and 3D
      electric and magnetic fields. The V point, at which two circular polarization
      singularities with the same topological charge but opposite handedness collide,
      appears in the 2D electric field under certain conditions in the diffraction
      field and free-space propagation. A comparison with the free-space propagation is
      also made. 

PMID- 24323226
TI  - Efficient three-dimensional ray-tracing model for electromagnetic propagation
      prediction in complex indoor environments.
AB  - A three-dimensional ray-tracing model for the use of the uniform theory of
      diffraction and geometrical optics in radio channel characterizations of indoor
      environments is presented in this paper. Based on the environment information
      chosen by the proposed modeling approach, the model is effectively applied by
      utilizing a technique in which multiple reflections, transmissions, and
      diffractions are considered via the ray-path classification into four different
      categories. Ray paths belonging to each ray category are determined by using
      different methods. Our theoretical results are compared with narrowband and
      wideband measurements. The good agreement with these measurements indicates that
      our prediction model works well for such indoor communication applications. 

PMID- 24323227
TI  - Electromagnetic scattering by a uniaxial anisotropic sphere located in an off
      axis Bessel beam.
AB  - Electromagnetic scattering of a zero-order Bessel beam by an anisotropic
      spherical particle in the off-axis configuration is investigated. Based on the
      spherical vector wave functions, the expansion expression of the zero-order
      Bessel beam is derived, and its convergence is numerically discussed in detail.
      Utilizing the tangential continuity of the electromagnetic fields, the
      expressions of scattering coefficients are given. The effects of the conical
      angle of the wave vector components of the zero-order Bessel beam, the ratio of
      the radius of the sphere to the central spot radius of the zero-order Bessel
      beam, the shift of the beam waist center position along both the x and y axes,
      the permittivity and permeability tensor elements, and the loss of the sphere on
      the radar cross section (RCS) are numerically analyzed. It is revealed that the
      maximum RCS appears in the conical direction or neighboring direction when the
      sphere is illuminated by a zero-order Bessel beam. Furthermore, the RCS will
      decrease and the symmetry is broken with the shift of the beam waist center. 

PMID- 24323228
TI  - Compensation of the two-stage phase-shifting algorithms in the presence of
      detuning and harmonics.
AB  - The Fourier analysis of two-stage phase-shifting (TSPS) algorithms is growing in
      interest as a research topic, specifically, the algorithm's insensitivity
      properties to various error sources. The main motivation of this paper is to
      propose TSPS algorithms that perform well in the face of detuning and harmonics
      for each of the two sets of interferograms with different or equal reference
      frequencies. TSPS algorithms based on the development of generalized equations
      consider both the frequency sampling functions that represent them and
      nonconstant phase shifts. 

PMID- 24323229
TI  - Kaczmarz algorithm for multiconjugated adaptive optics with laser guide stars.
AB  - We recently introduced the Kaczmarz algorithm for solving the atmospheric
      tomography problem in multiconjugate adaptive optics (MCAO). This iterative
      method solves the problem significantly faster than the standard matrix vector
      multiplication. We present the algorithm as well as an extension, which includes
      the effects of laser guide stars, such as the cone effect, tip/tilt
      indetermination, and spot elongation. We show that we can successfully cope with
      these effects and that the algorithm is suited for an MCAO system for the future
      generation of extremely large telescopes. 

PMID- 24323230
TI  - Locally countable properties and the perceptual salience of textures.
AB  - The human ability to discriminate structured from uniformly random binary
      textures has been shown to exploit third- and higher-order pixel correlations. We
      examine this ability in an experiment using a large number of texture families
      that can only be distinguished on the basis of these higher-order correlations.
      This study investigates statistical models based on possible explanatory
      variables involving spatial interactions of up to four pixels. Some of these
      explanatory variables have been recently associated with natural images, and
      others are somewhat less intuitive and are used here for the first time, to our
      knowledge. Our models are constructed using intraclass and cross-class feature
      selection by means of lasso/elastic net optimization and extensive cross
      validation. We focus on a special set of locally countable image measures that
      seem to parsimoniously capture the observed discrimination performance. Among the
      measures underpinning the best models, we highlight a concept that can only exist
      in nine-pixel or larger image patches, but nonetheless is calculable based on the
      multiplicity of specific four-pixel patches in a texture. We show that this
      single geometric concept provides significant clues to explain texture
      discrimination. 

PMID- 24323231
TI  - Design and rigorous analysis of transformation-optics scaling devices.
AB  - Scaling devices that can shrink or enlarge an object are designed using
      transformation optics. The electromagnetic scattering properties of such scaling
      devices with anisotropic parameters are rigorously analyzed using the eigenmode
      expansion method. If the radius of the virtual object is smaller than that of the
      real object, it is a shrinking device with positive material parameters; if the
      radius of the virtual object is larger than the real one, it is an enlarging
      device with positive or negative material parameters. Hence, a scaling device can
      make a dielectric or metallic object look smaller or larger. The rigorous
      analysis shows that the scattering coefficients of the scaling devices are the
      same as those of the equivalent virtual objects. When the radius of the virtual
      object approaches zero, the scaling device will be an invisibility cloak. In such
      a case, the scattering effect of the scaling device will be sensitive to material
      parameters of the device. 

PMID- 24323232
TI  - Optical modeling techniques for multimode horn-coupled power detectors for
      submillimeter and far-infrared astronomy.
AB  - An important class of detectors for the submillimeter and far-infrared uses a
      multimode horn to couple incident radiation into an absorbing film made from a
      thin conductor. We consider how to model the full, partially coherent, optical
      behavior of these multimode detectors using extensions of mode-matching
      techniques. We validate modeling the absorber as a resistive sheet, and
      demonstrate the equivalence of mode-matching and Green's function methods for
      calculating the scattering matrix representation of the film. Finally, we show
      how the scattering matrix of the film can be cascaded with those of the other
      components, as determined by mode matching, so as to calculate the overall
      optical response of the detector. Simulations are presented of the optical
      behavior of a square absorbing film in a circular waveguide. 

PMID- 24323233
TI  - High performance organic photovoltaics with zinc oxide and graphene oxide buffer
      layers.
AB  - We report air stable inverted organic photovoltaics (OPVs) incorporating graphene
      oxide (GO) and solution processed zinc oxide (ZnO) as hole transport and electron
      transport layers, respectively. Both the hole transport layer and the electron
      transport layer (HTL and ETL) are of advantage in high transparency and
      environmental stability. The use of GO and ZnO in poly(2,7-carbazole) derivative
      (PCDTBT):fullerene derivative (PC70BM)-based inverted OPVs leads to an improved
      device stability and enhanced high open circuit voltage (V(oc)) of 0.81 V, a
      short-circuit current density (J(sc)) of 14.10 mA cm(-2), and a fill factor (FF)
      of 54.44 along with a power conversion efficiency of 6.20%.

PMID- 24323234
TI  - Synthesis of substituted indenones and indanones by a Suzuki-Miyaura
      coupling/acid-promoted cyclisation sequence.
AB  - A one-pot Suzuki-Miyaura cross-coupling/acid-catalyzed cyclisation leading to
      indenones and indanones in modest to good yields is reported. 

PMID- 24323235
TI  - Supplementary feeding in programmes in developing countries: lessons of the
      eighties.
AB  - This extensive report reviews the important lessons learned during the 1980s on
      supplementary food distribution for the vulnerable groups in developing
      countries. These lessons may be useful in making such programmes a more cost
      effective option in narrowing the food/nutrient gap in intake among the programme
      beneficiaries. This report follows a similar report published at the end of the
      1970s by the author and George Beaton for UNICEF. The primary focus in the study
      has been the food distribution among young children, particularly schoolchildren,
      and also in pregnant and lactating women. The data have been gathered through a
      comprehensive search of the literature, official reports and documents from
      several United Nations agencies, aid agencies, national and international
      institutions. As well as original research papers on theoretical and applied
      issues, reports on design and evaluation of specific programmes in over 20
      countries are studied. Consideration of programme design examines objectives,
      nutrient/food gap, poverty reduction, malnutrition, mother and child feeding
      practices, foods, ration sizes, leakages, targeting, coverage, integration of
      feeding and health care. Potential and measured benefits are considered in the
      light of the reports published at the end of the 1970s and consequent analysis of
      work up until the end of the 1980s. Programme costs are documented. In a
      discussion on context and input, the functional significance of mild and moderate
      malnutrition is considered, together with diet and physical activity. The author
      offers some thoughts on future directions and high-lights the need for further
      research. 

PMID- 24323236
TI  - Insulin-like growth factor-I and fast growth-hormone levels in mild and
      moderately malnourished children.
AB  - Insulin-like growth factor-I (IGF-I)and fasting growth hormone levels were
      measured in a group of 255 children (163 males and 92 females. age ranged 6-17
      years) of varying pubertal development and body mass index (BMI); well-nourished
      (BMI> 18). mildly-malnourished (BMI = 15-18) and moderately-malnourished
      (BMI<15). In well-nourished children IGF-I levels increased significantly (P =
      0.02) with pubertal development. where girls at Tanner 5 had significantly higher
      (p = 0.03) IGF-I levels than the boys. Whilst there was no change in fasting GH
      levels with nutritional status, IGF-I levels of prepubertal boys and girls
      decreased significantly with BMI (P<0.001 and P = 0.01 respectively). Hence.
      measurement of IGF-I levels is a sensitive biochemical index in the assessment of
      mild and moderate form of malnutrition in prepubertal children. 

PMID- 24323237
TI  - A food frequency questionnaire for use in Chinese populations and its validation.
AB  - There is no gold standard in the assessment of individual dietary intake
      methodology. The choice of dietary method to estimate individual intake depends
      upon the study objectives for the assessment of individual intake. We adopted a
      food frequency questionnaire and modified it for use in a study of food habits
      and cardiovascular health status in adult Chinese living in Melbourne. Australia.
      This is a semi-quantitative questionnaire (MCHS-FFQ) and is designed to estimate
      past food intake. It consists of 220 foods and beverages. A reference portion is
      given to obtain a quantitative estimate of the usual intake portion. Various
      internal validation tests were performed. The MCHS-FFQ, being a food frequency
      dietary method, does not provide a good estimate of nutrients in foods which are
      not served in standard portions. such as sodium. The MCHS-FFQ offered a good
      estimate for potassium and protein intake when compared to estimates derived from
      a single 24-h urine collection. Finally, the MCHS-FFQ was predictive of plasma
      cholesterol levels. We conclude that the MCHS-FFQ is adequate for the assessment
      of individual usual food and nutrient intakes in a representative sample of adult
      Melbourne Chinese. For foods that are not served in a standard portion or
      quantifiable addition, an alternative more reliable method would be required for
      quantitative purposes. The method is. however, likely to be useful for the
      appraisal of overall food patterns in Chinese populations. 

PMID- 24323238
TI  - Colostrum avoidance and early infant feeding in Asian societies.
AB  - A review of the literature on childbirth and early infant feeding in Asian
      societies indicates that the avoidance of colostrum and the introduction of other
      foods at a very early age are both widespread and persistent. These traditional
      attitudes should be recognized where there are attempts to reduce infant
      mortality and morbidity. Further research into these practices is suggested. 

PMID- 24323239
TI  - Trends in the development of Thailand's nutrition and health plans and programs.
AB  - Thailand's achievements in health and social development, since its First
      National Economic Development Plan (1961) and those of its National Food and
      Nutrition Plans beginning in the Fourth National Economic and Social Development
      Plan (1977), have received worldwide acclaim. During the last decade the nation
      has experienced dramatic results in reducing protein-energy malnutrition (PEM),
      including the virtual eradication of severe PEM. Children and adults alike have
      better access to health care services, preventive and curative, during the past
      decade as Thailand's poverty alleviation, primary health care and quality of life
      approaches have reached out into even the remotest of rural villages. This paper
      explores the reasons behind this successful effort with special reference to how
      Thailand integrated nutrition plans into national health and rural development
      policies and programs. 

PMID- 24323240
TI  - Iron fortified salt distribution through integrated child development services in
      Orissa - an assessment.
AB  - The present study was undertaken in two backward districts namely Phulbani and
      Sundargarh, of Orissa State, India, to study operational aspects of the
      distribution programme of iron fortified salt (IFS), and the extent of any
      overlap with the ongoing National Nutritional Anaemia Control Programme (NNACP)
      and possible toxic effects thereof. All IFS samples tested showed iron levels in
      the range of 800-1000 mg of elemental iron per I kg of iron fortified salt.
      Distribution of IFS to households was irregular and only 40% of the households
      had stocks of IFS at the time of home visits. None of the households using IFS
      reported any kind of adverse effects. Prevalence of anaemia (blood haemoglobin
      level of less than 11 g/dl) was highest among pregnant women (90.9%) followed by
      lactating women (88.7%), school aged children (84.4%) and preschool children
      (77.9%) respectively. Folifer tablets are being distributed to pregnant,
      lactating women and preschool children. Adult tablets contain 60 mg of elemental
      iron in the form of ferrous sulphate (FeSO4) and 500 m g of folic acid. Tablets
      distributed to children contain 20 mg of elemental iron and 100 m g of folic
      acid. Enquires regarding distribution of folifer tablets showed that 71% of
      pregnant women, 22% of lactating women and 22% of children received the folifer
      tablets at sometime or other and no toxic effects were reported. These results
      indicate the necessity for some modifications in existing strategies for
      distribution of IFS in order that it be effective in the prevention of widespread
      anaemia. 

PMID- 24323241
TI  - The effectiveness of 50% lactose-reduced milk in alleviating milk intolerance.
AB  - The level of lactose reduction in milk necessary to alleviate the signs and
      symptoms of lactose intolerance has received little study. The purpose of this
      study was to determine whether 50% lactose-reduction in milk is adequate to
      alleviate the signs and symptoms of lactose maldigestion. even when large amounts
      of milk are consumed. Seven healthy subjects with proven lactose maldigestion
      consumed graded doses of whole cow's milk and 50% lactose reduced (LR) whole milk
      to determine the amount which could be consumed before breath hydrogen rose >20
      ppm. This threshold was exceeded on average with 500 ml of 50% LR milk and 200 ml
      of whole milk. Whole milk produced significantly more breath hydrogen (P<0.05)
      and maldigestion symptoms (P<0.05) at all levels than the 50% LR milk. These
      results suggest that milk with as little as 50% lactose reduction can play a
      major role in the diet of individuals with lactase deficiency. 

PMID- 24323242
TI  - Localized myopathy in a young man with abetalipoproteinaemia-myocardial
      infarction?
AB  - Myocardial infarction has not previously been reported as a complication of
      abetalipoproteinaemia (ABL) We describe a case of probable asymptomatic
      myocardial infarction in a 24-year-old male with ABL and no previous cardiac
      history . Electrocardiographic and imaging evidence of the injury is presented. 

PMID- 24323243
TI  - De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than
      previously assumed.
AB  - AIMS/HYPOTHESIS: MODY is mainly characterised by an early onset of diabetes and a
      positive family history of diabetes with an autosomal dominant mode of
      inheritance. However, de novo mutations have been reported anecdotally. The aim
      of this study was to systematically revisit a large collection of MODY patients
      to determine the minimum prevalence of de novo mutations in the most prevalent
      MODY genes (i.e. GCK, HNF1A, HNF4A). METHODS: Analysis of 922 patients from two
      national MODY centres (Slovakia and the Czech Republic) identified 150 probands
      (16%) who came from pedigrees that did not fulfil the criterion of two
      generations with diabetes but did fulfil the remaining criteria. The GCK, HNF1A
      and HNF4A genes were analysed by direct sequencing. RESULTS: Mutations in GCK,
      HNF1A or HNF4A genes were detected in 58 of 150 individuals. Parents of 28
      probands were unavailable for further analysis, and in 19 probands the mutation
      was inherited from an asymptomatic parent. In 11 probands the mutations arose de
      novo. CONCLUSIONS/INTERPRETATION: In our cohort of MODY patients from two
      national centres the de novo mutations in GCK, HNF1A and HNF4A were present in
      7.3% of the 150 families without a history of diabetes and 1.2% of all of the
      referrals for MODY testing. This is the largest collection of de novo MODY
      mutations to date, and our findings indicate a much higher frequency of de novo
      mutations than previously assumed. Therefore, genetic testing of MODY could be
      considered for carefully selected individuals without a family history of
      diabetes.

PMID- 24323244
TI  - Randomized controlled trial of physical activity, cognition, and walking in
      multiple sclerosis.
AB  - The present study adopted a randomized controlled trial design and examined the
      effect of a physical activity behavioral intervention on cognitive and walking
      performance among persons with MS who have mild or moderate disability status. A
      total of 82 MS patients were randomly allocated into intervention or wait-list
      control conditions. The intervention condition received a theory-based program
      for increasing physical activity behavior that was delivered via the Internet,
      and one-on-one video chat sessions with a behavior-change coach. Participants
      completed self-report measures of physical activity and disability status, and
      underwent the oral Symbol Digit Modalities Test (SDMT) and 6-minute walk (6MW)
      test before and after the 6-month period. Analysis using mixed-model ANOVA
      indicated a significant time * condition * disability group interaction on SDMT
      scores (p = 0.02, partial-eta (2) = 0.08), such that persons with mild disability
      in the intervention condition demonstrated a clinically meaningful improvement in
      SDMT scores (~6 point change). There was a further significant time * condition
      interaction on 6MW distance (p = 0.02, partial-eta (2) = 0.07), such that those
      in the intervention condition demonstrated an increase in 6MW distance relative
      to those in the control group. The current study supports physical activity as a
      promising tool for managing cognitive impairment and impaired walking performance
      in persons with MS, and suggests that physical activity might have specific
      effects on cognition and non-specific effects on walking performance in this
      population. 

PMID- 24323245
TI  - A Japanese family with idiopathic basal ganglia calcification with novel SLC20A2
      mutation presenting with late-onset hallucination and delusion.

PMID- 24323246
TI  - Pollinator shifts as triggers of speciation in painted petal irises (Lapeirousia:
      Iridaceae).
AB  - BACKGROUND AND AIMS: Adaptation to different pollinators has been hypothesized as
      one of the main factors promoting the formation of new species in the Cape region
      of South Africa. Other researchers favour alternative causes such as shifts in
      edaphic preferences. Using a phylogenetic framework and taking into consideration
      the biogeographical scenario explaining the distribution of the group as well as
      the distribution of pollinators, this study compares pollination strategies with
      substrate adaptations to develop hypotheses of the primary factors leading to
      speciation in Lapeirousia (Iridaceae), a genus of corm-bearing geophytes well
      represented in the Cape and presenting an important diversity of pollination
      syndromes and edaphic preferences. METHODS: Phylogenetic relationships are
      reconstructed within Lapeirousia using nuclear and plastid DNA sequence data.
      State-of-the-art methods in biogeography, divergence time estimation, character
      optimization and diversification rate assessments are used to examine the
      evolution of pollination syndromes and substrate shifts in the history of the
      group. Based on the phylogenetic results, ecological factors are compared for
      nine sister species pairs in Lapeirousia. KEY RESULTS: Seventeen pollinator
      shifts and ten changes in substrate types were inferred during the evolution of
      the genus Lapeirousia. Of the nine species pairs examined, all show divergence in
      pollination syndromes, while only four pairs present different substrate types.
      CONCLUSIONS: The available evidence points to a predominant influence of
      pollinator shifts over substrate types on the speciation process within
      Lapeirousia, contrary to previous studies that favoured a more important role for
      edaphic factors in these processes. This work also highlights the importance of
      biogeographical patterns in the study of pollination syndromes.

PMID- 24323249
TI  - Silver nanoparticles supported on alumina--a highly efficient and selective
      nanocatalyst for imine reduction.
AB  - Silver nanoparticles supported on alumina were prepared and tested in the
      catalytic reduction of various imines to primary and secondary amines and were
      shown to be exceptionally active and chemoselective. Furthermore, the catalytic
      activity of the prepared nanocatalyst was also tested in the synthesis of
      secondary amines from primary amines in a tandem reaction protocol (oxidation
      imination-reduction) using air and molecular hydrogen as oxidizing and reducing
      agents, respectively. The reported synthesis is performed under mild reaction
      conditions, which complies with the demands of modern organic synthesis. Due to
      the mild reaction conditions and high conversion as well as high selectivity, we
      consider that the utilization of silver nanoparticles supported on alumina
      represents an attractive and environmentally friendly alternative to the current
      synthesis of N-alkyl amines. 

PMID- 24323248
TI  - Response of tree growth and species coexistence to density and species evenness
      in a young forest plantation with two competing species.
AB  - BACKGROUND AND AIMS: There is considerable evidence for the presence of positive
      species diversity-productivity relationships in plant populations, but the
      population parameters determining the type and strength of the relationship are
      poorly defined. Relationships between species evenness and tree survival or
      species coexistence are not well established. The objective of this study was to
      quantify the joint effects of density and species evenness on tree productivity
      and species coexistence. METHODS: A 12-year-old experimental tree plantation
      mixing two species according to a double gradient of density and species
      proportion was used. A neighbourhood approach was employed and descriptors of
      local competition were used to model individual tree growth. Fagus sylvatica and
      Acer pseudoplatanus were used as model species, as they can be considered as
      ecologically equivalent in their young stages. KEY RESULTS: Density and tree size
      were primary factors determining individual growth and stand productivity.
      Species identity had a significant, but less pronounced, role. Stand productivity
      was highest when species evenness was close to 1 and slightly lower in uneven
      mixtures. The reduction in stand productivity when species evenness decreased was
      of similar magnitude irrespective of which species became dominant, indicating
      symmetric effects for the two species. When examining individual tree growth in
      response to species proportion for each species separately, it was observed for
      both species that individual trees exhibited greater growth in uneven mixtures in
      which the other species was more frequent. CONCLUSIONS: The results suggest that
      mixtures of these two functionally similar species have the highest production at
      maximum evenness, indicating a complementary effect between them. The presence of
      a mixture combines both stabilizing mechanisms (individuals from both species
      show higher growth when surrounded by individuals from the other species) and
      equalizing mechanisms (the two species have very similar growth curves) that, in
      turn, determine the species' relative dominance. These processes should act to
      ensure the long-term coexistence of species.

PMID- 24323247
TI  - Comparative analysis of the cold acclimation and freezing tolerance capacities of
      seven diploid Brachypodium distachyon accessions.
AB  - BACKGROUND AND AIMS: Cold is a major constraint for cereal cultivation under
      temperate climates. Winter-hardy plants interpret seasonal changes and can
      acquire the ability to resist sub-zero temperatures. This cold acclimation
      process is associated with physiological, biochemical and molecular alterations
      in cereals. Brachypodium distachyon is considered a powerful model system to
      study the response of temperate cereals to adverse environmental conditions. To
      date, little is known about the cold acclimation and freezing tolerance
      capacities of Brachypodium. The main objective of this study was to evaluate the
      cold hardiness of seven diploid Brachypodium accessions. METHODS: An integrated
      approach, involving monitoring of phenological indicators along with expression
      profiling of the major vernalization regulator VRN1 orthologue, was followed. In
      parallel, soluble sugars and proline contents were determined along with
      expression profiles of two COR genes in plants exposed to low temperatures.
      Finally, whole-plant freezing tests were performed to evaluate the freezing
      tolerance capacity of Brachypodium. KEY RESULTS: Cold treatment accelerated the
      transition from the vegetative to the reproductive phase in all diploid
      Brachypodium accessions tested. In addition, low temperature exposure triggered
      the gradual accumulation of BradiVRN1 transcripts in all accessions tested. These
      accessions exhibited a clear cold acclimation response by progressively
      accumulating proline, sugars and COR gene transcripts. However, whole-plant
      freezing tests revealed that these seven diploid accessions only have a limited
      capacity to develop freezing tolerance when compared with winter varieties of
      temperate cereals such as wheat and barley. Furthermore, little difference in
      terms of survival was observed among the accessions tested despite their previous
      classification as either spring or winter genotypes. CONCLUSIONS: This study is
      the first to characterize the freezing tolerance capacities of B. distachyon and
      provides strong evidence that some diploid accessions such as Bd21 have a
      facultative growth habit.

PMID- 24323251
TI  - Giant circular polarization conversion in layer-by-layer nonchiral metamaterial.
AB  - We studied numerically the transmission properties of a kind of layer-by-layer
      nonchiral metamaterial. Simulation results show that under certain off-normal
      incidence, giant circular polarization conversion occurs for both the right and
      left circularly polarized waves with a roughly 1 GHz operation band. Meanwhile,
      the copolarization transmissions are almost suppressed to zero, leading to the
      high purity circular polarization transformation. This phenomenon of giant
      circular polarization conversion is assumed to suffer from the strong magnetic
      response, which is illustrated by the surface current distributions of the
      structure. Compared with chiral structures, this nonchiral structure is easier to
      design and fabricate and is expected to be used as a promising circular
      polarization transformer.

PMID- 24323252
TI  - Aspherical lens design.
AB  - Given a three-dimensional surface G, not necessarily rotationally symmetric, and
      away from a point source, we design a surface F such that the lens sandwiched
      between the two surfaces refracts radiation into a given direction or into a
      given point. The surface F satisfies a system of first-order partial differential
      equations that can be solved in terms of G and the refractive indices of the
      media involved. 

PMID- 24323250
TI  - Early physiological and biochemical responses of rice seedlings to low
      concentration of microcystin-LR.
AB  - Microcystin-leucine and arginine (microcystin-LR) is a cyanotoxin produced by
      cyanobacteria like Microcystis aeruginosa, and it's considered a threat to water
      quality, agriculture, and human health. Rice (Oryza sativa) is a plant of great
      importance in human food consumption and economy, with extensive use around the
      world. It is therefore important to assess the possible effects of using water
      contaminated with microcystin-LR to irrigate rice crops, in order to ensure a
      safe, high quality product to consumers. In this study, 12 and 20-day-old plants
      were exposed during 2 or 7 days to a M. aeruginosa extract containing
      environmentally relevant microcystin-LR concentrations, 0.26-78 MUg/L. Fresh and
      dry weight of roots and leaves, chlorophyll fluorescence, glutathione S
      transferase and glutathione peroxidase activities, and protein identification by
      mass spectrometry through two-dimensional gel electrophoresis from root and leaf
      tissues, were evaluated in order to gauge the plant's physiological condition and
      biochemical response after toxin exposure. Results obtained from plant biomass,
      chlorophyll fluorescence, and enzyme activity assays showed no significant
      differences between control and treatment groups. However, proteomics data
      indicates that plants respond to M. aeruginosa extract containing environmentally
      relevant microcystin-LR concentrations by changing their metabolism, responding
      differently to different toxin concentrations. Biological processes most affected
      were related to protein folding and stress response, protein biosynthesis, cell
      signalling and gene expression regulation, and energy and carbohydrate metabolism
      which may denote a toxic effect induced by M. aeruginosa extract and microcystin
      LR. The implications of the metabolic alterations in plant physiology and growth
      require further elucidation. 

PMID- 24323253
TI  - Propagation-inside-layer-expansion method combined with physical optics for
      scattering by coated cylinders, a rough layer, and an object below a rough
      surface.
AB  - In this article, the fields scattered by coated cylinders, a rough layer, and an
      object below a rough surface are computed by the efficient propagation-inside
      layer-expansion (PILE) method combined with the physical optics (PO)
      approximation to accelerate the calculation of the local interactions on the non
      illuminated scatterer, which is assumed to be perfectly conducting. The PILE
      method is based on the method of moments, and the impedance matrix of the two
      scatterers is then inverted by blocks from a Taylor series expansion of the
      inverse of the Schur complement. Its main interest is that it is rigorous, with a
      simple formulation and a straightforward physical interpretation. In addition,
      one of the advantages of PILE is to be able to hybridize methods (rigorous or
      asymptotic) valid for a single scatterer. Then, in high frequencies, the
      hybridization with PO allows us to significantly reduce the complexity in
      comparison to a direct lower-upper inversion of the impedance matrix of the two
      scatterers without loss in accuracy. 

PMID- 24323254
TI  - Analysis of optical waves propagating through moderate-to-strong non-Kolmogorov
      turbulence.
AB  - The turbulence effect models derived with the Rytov theory method cannot be
      applied in the analysis of moderate-to-strong non-Kolmogorov turbulence. In this
      work, new expressions of the temporal power spectra of irradiance fluctuations
      are derived theoretically for optical waves propagating through moderate-to
      strong non-Kolmogorov turbulence. They are developed under Andrews' assumption
      that small-scale irradiance fluctuations are modulated by large-scale irradiance
      fluctuations of the optical wave. A wide range of turbulence strength is
      considered instead of a limited range for weak non-Kolmogorov turbulence. These
      expressions have general spectral power law values in the range 3 to 4 instead of
      the standard power law value of 11/3 for Kolmogorov turbulence. Calculations are
      performed to analyze turbulence strength and turbulence spectral power law's
      variations on the final expressions. 

PMID- 24323255
TI  - Enhanced method for determining the optical response of highly complex biological
      photonic structures.
AB  - We present a set of techniques that enhances a previously developed time domain
      simulation of wave propagation and allows the study of the optical response of a
      broad range of dielectric photonic structures. This method is particularly
      suitable for dealing with complex biological structures, especially due to the
      simple and intuitive way of defining the setup and the photonic structure to be
      simulated, which can be done via a digital image of the structure. The presented
      techniques include a direction filter that permits the decoupling of waves
      traveling simultaneously in different directions, a dynamic differential absorber
      to cancel the waves reflected at the edges of the simulation space, and a
      multifrequency excitation scheme. We also show how the simulation can be adapted
      to apply a near to far field method in order to evaluate the resulting wavefield
      outside the simulation domain. We validate these techniques, and, as an example,
      we apply the method to the complex structure of a microorganism called Diachea
      leucopoda, which exhibits a multicolor iridescent appearance. 

PMID- 24323256
TI  - Optical schemes for speckle suppression by Barker code diffractive optical
      elements.
AB  - A method for speckle suppression based on Barker code and M-sequence code
      diffractive optical elements (DOEs) is analyzed. An analytical formula for the
      dependence of speckle contrast on the wavelength of the laser illumination is
      derived. It is shown that speckle contrast has a wide maximum around the optimal
      wavelength that makes it possible to obtain large speckle suppression by using
      only one DOE for red, green, and blue laser illumination. Optical schemes for
      implementing this method are analyzed. It is shown that the method can use a
      simple liquid-crystal panel for phase rotation instead of a moving DOE; however,
      this approach requires a high frequency of liquid-crystal switching. A simple
      optical scheme is proposed using a 1D Barker code DOE and a simple 1D liquid
      crystal panel, which does not require a high frequency of liquid-crystal
      switching or high-accuracy DOE movement. 

PMID- 24323257
TI  - Optimal design and fabrication method for antireflection coatings for P-polarized
      193 nm laser beam at large angles of incidence (68 degrees -74 degrees ).
AB  - Most of the optical axes in modern systems are bent for optomechanical
      considerations. Antireflection (AR) coatings for polarized light at oblique
      incidence are widely used in optical surfaces like prisms or multiform lenses to
      suppress undesirable reflections. The optimal design and fabrication method for
      AR coatings with large-angle range (68 degrees -74 degrees ) for a P-polarized
      193 nm laser beam is discussed in detail. Experimental results showed that after
      coating, the reflection loss of a P-polarized laser beam at large angles of
      incidence on the optical surfaces is reduced dramatically, which could greatly
      improve the output efficiency of the optical components in the deep ultraviolet
      vacuum range.

PMID- 24323258
TI  - Surface and bulk scattering by magnetic and dielectric inhomogeneities: a first
      order method.
AB  - The scattering of a magnetodielectric multilayer has been studied by a first
      order method. The model reported in this manuscript relies on the equivalence
      between heterogeneities of the medium and fictitious electric and magnetic
      sources. Types of inhomogeneities considered are roughness and bulk
      inhomogeneities and concern both permittivity and permeability. The numerical
      results are compared to those given in previous papers for optical scattering. It
      is shown in the microwave spectra that angle-resolved scattering allows
      identification of the scattering origins (permittivity or permeability spectra).
      The cases of isotropic films and metamaterials are presented and discussed. 

PMID- 24323259
TI  - Effects of high-color-discrimination capability spectra on color-deficient
      vision.
AB  - Light sources with three spectral bands in specific spectral positions are known
      to have high-color-discrimination capability. W. A. Thornton hypothesized that
      they may also enhance color discrimination for color-deficient observers. This
      hypothesis was tested here by comparing the Rosch-MacAdam color volume for color
      deficient observers rendered by three of these singular spectra, two reported
      previously and one derived in this paper by maximization of the Rosch-MacAdam
      color solid. It was found that all illuminants tested enhance discriminability
      for deuteranomalous observers, but their impact on other congenital deficiencies
      was variable. The best illuminant was the one derived here, as it was clearly
      advantageous for the two red-green anomalies and for tritanopes and almost
      neutral for red-green dichromats. We conclude that three-band spectra with high
      color-discrimination capability for normal observers do not necessarily produce
      comparable enhancements for color-deficient observers, but suitable spectral
      optimization clearly enhances the vision of the color deficient. 

PMID- 24323260
TI  - Rational-operator-based depth-from-defocus approach to scene reconstruction.
AB  - This paper presents a rational-operator-based approach to depth from defocus
      (DfD) for the reconstruction of three-dimensional scenes from two-dimensional
      images, which enables fast DfD computation that is independent of scene textures.
      Two variants of the approach, one using the Gaussian rational operators (ROs)
      that are based on the Gaussian point spread function (PSF) and the second based
      on the generalized Gaussian PSF, are considered. A novel DfD correction method is
      also presented to further improve the performance of the approach. Experimental
      results are considered for real scenes and show that both approaches outperform
      existing RO-based methods. 

PMID- 24323261
TI  - Patterns with different phases but same statistics.
AB  - Many successful methods in various vision tasks rely on statistical analysis of
      visual patterns. However, we are interested in covering the gap between the
      underlying mathematical representation of the visual patterns and their
      statistics. With this general trend, in this paper a relationship between phase
      structure of a class of patterns and their moments after and before filtering
      have been considered. First, a general formula between the phase structure and
      moments of the images is obtained. Second, a theorem is developed that states
      under which conditions two visual patterns with the same frequencies but
      different phases have the same moments up to a certain moment. Finally, a theorem
      is developed that explains, given a set of filters, under which conditions two
      visual patterns with both different frequencies and different phases have the
      same subband statistics. 

PMID- 24323262
TI  - Eigenvectors of optimal color spectra.
AB  - Principal component analysis (PCA) and weighted PCA were applied to spectra of
      optimal colors belonging to the outer surface of the object-color solid or to so
      called MacAdam limits. The correlation matrix formed from this data is a
      circulant matrix whose biggest eigenvalue is simple and the corresponding
      eigenvector is constant. All other eigenvalues are double, and the eigenvectors
      can be expressed with trigonometric functions. Found trigonometric functions can
      be used as a general basis to reconstruct all possible smooth reflectance
      spectra. When the spectral data are weighted with an appropriate weight function,
      the essential part of the color information is compressed to the first three
      components and the shapes of the first three eigenvectors correspond to one
      achromatic response function and to two chromatic response functions, the latter
      corresponding approximately to Munsell opponent-hue directions 9YR-9B and 2BG-2R.

PMID- 24323263
TI  - Explicit representations of all refractive optical interfaces without spherical
      aberration.
AB  - The following explicit model, valid for high aperture refraction with homogenous
      and isotropic materials, encompasses all explicit solutions of the first-order
      nonlinear differential equation representing the perfect image-forming process of
      any axial object point into its axial image point. Solutions include well-known
      cases, such as flats, spheres, prolate ellipsoids, prolate hyperboloids, and
      other sections of nondegenerate Cartesian ovals of revolution, now classified
      according to the recurrent explicit solution introduced herein. We also present
      some series expansions, given in cylindrical coordinates z(r), for more efficient
      computation. Explicit solutions allow accurate and expedite thickness calculation
      as compared to the regular series, parametric, or implicit solutions commonly
      used. The results of this study are useful in the design of centered optical
      systems that are perfectly aligned. 

PMID- 24323264
TI  - Approach for fast numerical propagation of uniformly polarized random
      electromagnetic fields in dispersive linearly birefringent systems.
AB  - An efficient simulation technique is proposed for computing propagation of
      uniformly polarized statistically stationary fields in linear nonimage-forming
      systems that includes dispersion of linear birefringence to all orders. The
      method is based on the discrete-time Fourier transformation of modified frequency
      profiles of the spectral Stokes parameters. It works under the condition that all
      (linearly) birefringent sections present in the system are described by the same
      phase birefringence dispersion curve, being a monotonic function of the optical
      frequency within the bandwidth of the light. We demonstrate the technique as a
      supplement for the Mueller-Stokes matrix formalism extended to any uniformly
      polarized polychromatic illumination. Accuracy of its numerical implementation
      has been verified by using parameters of a Lyot depolarizer made of a highly
      birefringent and dispersive monomode photonic crystal fiber. 

PMID- 24323265
TI  - Closed-form solution to the scattering by an infinite lossless or lossy elliptic
      cylinder coating a circular metallic core.
AB  - An analytical, closed-form solution to the scattering problem from an infinite
      lossless or lossy elliptical cylinder coating a circular metal core is treated in
      this work. The problem is solved by expressing the electromagnetic field in both
      elliptical and circular wave functions, connected with one another by well-known
      expansion formulas. The procedure for solving the problem is cumbersome because
      of the nonexistence of orthogonality relations for Mathieu functions across the
      dielectric elliptical boundary. The solution obtained, which is free of Mathieu
      functions, is given in closed form, and it is valid for small values of the
      eccentricity h of the elliptical cylinder. Analytical expressions of the form
      S(h)=S(0)[1+g(2)h2+g(4)h4+O(h6] are obtained, permitting an immediate calculation
      for the scattering cross sections. The proposed method is an alternative one, for
      small h, to the standard exact numerical solution obtained after the truncation
      of the system matrices, composed after the satisfaction of the boundary
      conditions. Both polarizations are considered for normal incidence. The results
      are validated against the exact solution, and numerical results are given for
      various values of the parameters.

PMID- 24323266
TI  - Optical solver of combinatorial problems: nanotechnological approach.
AB  - We present an optical computing system to solve NP-hard problems. As nano-optical
      computing is a promising venue for the next generation of computers performing
      parallel computations, we investigate the application of submicron, or even
      subwavelength, computing device designs. The system utilizes a setup of
      exponential sized masks with exponential space complexity produced in polynomial
      time preprocessing. The masks are later used to solve the problem in polynomial
      time. The size of the masks is reduced to nanoscaled density. Simulations were
      done to choose a proper design, and actual implementations show the feasibility
      of such a system. 

PMID- 24323267
TI  - Ghost imaging with nonuniform thermal light fields.
AB  - In practical thermal light ghost imaging, the nonuniform intensity distribution
      of the thermal light applied causes distortion of the retrieved image. We propose
      uniformly weighted arithmetics, including uniformly weighted ghost imaging and
      uniformly weighted differential ghost imaging (UWDGI), to improve the imaging
      quality of ghost imaging with nonuniform thermal light fields. Two kinds of
      nonuniform thermal light fields are discussed, including planar Gaussian
      distributed thermal light and near-field three-dimensional thermal light. The
      retrieved image using a uniformly weighted arithmetic has a lower distortion than
      that using the corresponding traditional ghost imaging arithmetic. In addition,
      the best imaging quality is achieved with the UWDGI arithmetic. 

PMID- 24323268
TI  - Reconstruction of total radiance spectra of fluorescent samples by means of
      nonlinear principal component analysis.
AB  - Nonlinear principal component analysis (NLPCA) was used for compression and
      reconstruction of the total radiance factors (TRFs) of fluorescent samples. The
      spectral dataset included a total of 358 fluorescent reflectance spectra in the
      visible range of the spectrum. Spectral data compression was followed by
      extracting the parameterized nonlinear manifolds using the NLPCA technique. To
      compare the performance of NLPCA-based compression with the linear method, the
      orthonormal feature vectors of the dataset were also extracted by the linear PCA.
      The spectral performance of NLPCA and PCA-based compression approaches was
      assessed by the root mean square error and the goodness-fitting coefficient
      between the real and the reconstructed spectra. The percentages of feasible
      spectra by each method, i.e., those with nonnegative TRFs, were also reported as
      other criteria for the evaluation of methods. Furthermore, the colorimetric
      performance of methods were appraised by the measuring the CIELAB 1976 color
      difference values between the actual and reconstructed spectra under illuminants
      D65 and A and the 1964 standard observer. The NLPCA-based compression method
      performed significantly better than the standard PCA-based technique particularly
      in the lower dimensional spaces of the spectral radiance factors of fluorescent
      colors. 

PMID- 24323269
TI  - Effects of chromatic image statistics on illumination induced color differences.
AB  - We measure the color fidelity of visual scenes that are rendered under different
      (simulated) illuminants and shown on a calibrated LCD display. Observers make
      triad illuminant comparisons involving the renderings from two chromatic test
      illuminants and one achromatic reference illuminant shown simultaneously. Four
      chromatic test illuminants are used: two along the daylight locus (yellow and
      blue), and two perpendicular to it (red and green). The observers select the
      rendering having the best color fidelity, thereby indirectly judging which of the
      two test illuminants induces the smallest color differences compared to the
      reference. Both multicolor test scenes and natural scenes are studied. The
      multicolor scenes are synthesized and represent ellipsoidal distributions in
      CIELAB chromaticity space having the same mean chromaticity but different
      chromatic orientations. We show that, for those distributions, color fidelity is
      best when the vector of the illuminant change (pointing from neutral to
      chromatic) is parallel to the major axis of the scene's chromatic distribution.
      For our selection of natural scenes, which generally have much broader chromatic
      distributions, we measure a higher color fidelity for the yellow and blue
      illuminants than for red and green. Scrambled versions of the natural images are
      also studied to exclude possible semantic effects. We quantitatively predict the
      average observer response (i.e., the illuminant probability) with four types of
      models, differing in the extent to which they incorporate information processing
      by the visual system. Results show different levels of performance for the
      models, and different levels for the multicolor scenes and the natural scenes.
      Overall, models based on the scene averaged color difference have the best
      performance. We discuss how color constancy algorithms may be improved by
      exploiting knowledge of the chromatic distribution of the visual scene. 

PMID- 24323270
TI  - Kinetics of polarization gratings assisted with polarized violet light in
      bacteriorhodopsin films.
AB  - Polarization gratings can be recorded in bacteriorhodopsin films by an orthogonal
      pair of linearly or circularly polarized beams. If a linearly polarized auxiliary
      violet light is added during the grating formation, the grating becomes
      polarization-sensitive. A theoretical model based on the two-state photochromic
      theory is proposed to calculate the diffraction efficiency kinetics of these
      polarization gratings. In both cases, the additional linearly polarized auxiliary
      violet irradiation improves the steady-state diffraction efficiency and leads to
      a cosine modulation of the steady-state diffraction efficiency by the
      polarization orientation of the readout beam. Experiment results demonstrate the
      correctness of the theoretical model. 

PMID- 24323271
TI  - Absorption and scattering by long and randomly oriented linear chains of spheres.
AB  - This paper demonstrates that the scattering cross section per unit length of
      randomly oriented linear chains of optically soft spheres asymptotically
      converges toward those of randomly oriented and infinitely long cylinders with
      volume-equivalent diameter as the number of spheres increases. The critical
      number of spheres necessary to approximate the linear chains of spheres as
      infinitely long cylinders decreased rapidly as the size parameter of an
      individual sphere increased from 0.01 to 10. On the other hand, their absorption
      cross section per unit length was identical to that of an infinitely long volume
      equivalent cylinder for any number of spheres. However, this approximation does
      not apply to the angle-dependent normalized Stokes scattering matrix element
      ratios. 

PMID- 24323272
TI  - Conical reflection of light during free-space coupling into a symmetrical metal
      cladding waveguide.
AB  - Novel conical reflection of light by a thick three-layered metal-clad optical
      waveguide is observed. A symmetrical metal-cladding optical waveguide is used,
      which exhibits extraordinary conical reflection during free-space coupling of
      light to the waveguide. The phenomenon is attributed to the leakage of excited
      ultrahigh-order guided modes and their inter- and intramode coupling interaction.

PMID- 24323273
TI  - Injury and repair in the immature brain.

PMID- 24323274
TI  - Differentiation of oligodendrocytes from mouse induced pluripotent stem cells
      without serum.
AB  - Cell therapy using induced pluripotent stem (iPS) cells might become a new
      approach for treating neonatal hypoxic-ischemic injury such as periventricular
      leukomalacia. To obtain appropriate donor cells for transplantation, we
      differentiated oligodendrocyte (OL) lineage cells from mouse iPS cells. Induction
      of OL lineage cell differentiation from iPS cells was carried out with a seven
      step culture method. Mouse iPS cells (stage 1) were induced to form embryoid
      bodies for 4 days under a serum-free condition that was suitable for ectoderm
      induction (stage 2), following by selection of nestin-positive neural stem cells
      (NSCs) for 10-12 days (stage 3). NSCs were cultured in expansion medium
      containing fibroblast growth factor (FGF)-2 for 4 days (stage 4), induced to
      differentiate into glial progenitor cells by epidermal growth factor and
      fibroblast growth factor (FGF-2) treatment for 4-5 days (stage 5), and then into
      OL progenitor cells by culture in neurobasal A medium containing FGF-2 and
      platelet-derived growth factor for 6-8 days (stage 6). Terminal differentiation
      into O4-positive OLs was carried out by culture in neurobasal A containing T3 and
      ciliary neurotrophic factor for 7 days (stage 7). Inwardly rectifying K+
      currents, which are characteristic of OLs, were detected in iPS cell-derived
      cells at stage 7 in whole cell clamp mode. Our data suggest that OLs can be
      effectively differentiated from mouse iPS cells without serum in a stepwise
      manner, which may be appropriate for use as donor cells in transplantation.

PMID- 24323275
TI  - Inhaled nitric oxide protects males but not females from neonatal mouse hypoxia
      ischemia brain injury.
AB  - It was recently discovered that while under normal conditions inhaled nitric
      oxide (iNO) does not affect cerebral blood flow, it selectively dilates
      arterioles in the ischemic penumbra during experimental cerebral ischemia,
      thereby increasing collateral blood flow and reducing ischemic brain damage. The
      mechanism was verified in multiple models, but only in male animals. Our aim was
      to evaluate the effects of iNO on brain injury in neonatal males and females.
      Nine-day-old mice were subjected to unilateral hypoxia-ischemia (HI), using 10%
      oxygen balanced with nitrogen, with or without 50 ppm NO. Brain injury 72 h after
      HI was reduced by iNO as judged by percentage of injury (-21.7%), atrophy (
      23.7%), and total pathological score (-29%). The injury was significantly reduced
      in males (-32.4%, p<0.05) but not in females (-7.1%, n.s.). Neither the numbers
      nor the proliferation rates of neural stem cells in the dentate gyrus were
      affected by iNO. In summary, intraischemic iNO reduced neonatal HI brain injury
      in a gender-related manner.

PMID- 24323276
TI  - Comparison of three hypothermic target temperatures for the treatment of hypoxic
      ischemia: mRNA level responses of eight genes in the piglet brain.
AB  - Hypothermia can reduce neurodevelopmental disabilities in asphyxiated newborn
      infants. However, the optimal cooling temperature for neuroprotection is not well
      defined. We studied the effects of transient piglet brain hypoxic ischemia (HI)
      on transcriptional activity of eight genes and if mRNA level alterations could be
      counteracted by whole body cooling to 35, 33.5 or 30  degrees C. BDNF mRNA was
      globally upregulated by the insult, and none of the cooling temperatures
      counteracted this change. In contrast, MANF mRNA was downregulated, and these
      changes were modestly counteracted in different brain regions by hypothermic
      treatment at 33.5  degrees C, while 30  degrees C aggravated the MANF mRNA loss.
      MAP2 mRNA was markedly downregulated in all brain regions except striatum, and
      cooling to 33.5  degrees C modestly counteract this downregulation in the cortex
      cerebri. There was a tendency for GFAP mRNA levels in core, but not mantle
      regions to be downregulated and for these changes to be modestly counteracted by
      cooling to 33.5 or 35  degrees C. Cooling to 30  degrees C caused global GFAP
      mRNA decrease. HSP70 mRNA tended to become upregulated by HI and to be more
      pronounced in cortex and CA1 of hippocampus during cooling to 33.5  degrees C. We
      conclude that HI causes alterations of mRNA levels of many genes in superficial
      and deep piglet brain areas. Some of these changes may be beneficial, others
      detrimental, and lowering body temperature partly counteracts some, but not all
      changes. There may be general differences between core and mantle regions, as
      well as between the different cooling temperatures for protection. Comparing the
      three studied temperatures, cooling to 33.5  degrees C, appears to provide the
      best cooling temperature compromise. 

PMID- 24323278
TI  - Psychopathological profile and health-related quality of life (HRQOL) in patients
      with hepatocellular carcinoma (HCC) and cirrhosis.
AB  - In some tumors, psychosocial interventions may enhance health-related quality of
      life (HRQOL) of patients. The effects of psychological variables on HRQOL in
      hepatocellular carcinoma (HCC) patients have been rarely assessed. The aim of
      this work is to evaluate the psychopathological profile of HCC and cirrhotic
      patients and its effect on HRQOL. Twenty-four HCC patients (median age 71, Child
      A 21, Child B 3), 22 cirrhotic patients (median age 68, Child A 20, Child B 2)
      and 20 control subjects were included in this study. Each subject completes four
      questionnaires: medical outcomes study short form-36 (SF-36, HRQOL evaluation);
      Hamilton-D (quantitative evaluation of depression; positive >=8); symptom check
      list 90-revised (SCL 90-R, general psychopathological profile; nine domains, each
      positive >1); Toronto alexithymia scale (TAS 20) (positive >=60). SCL 90-R:
      cirrhotic patients differ from HCC subjects for somatization (SOM) (M +/- SD 1.09
      +/- 0.6 vs 0.65 +/- 0.6; p = 0.01) and anxiety (M +/- SD 0.85 +/- 0.46 vs 0.58 +/
      0.38; p = 0.01) items. TAS 20: positive in 50% of HCC patients, in 54% of
      cirrhotic patients (p = n.s.) and in none of controls. Hamilton-D: higher scores
      in cirrhotic patients than in the HCC group (86 vs 46%; p = 0.005). SF-36: each
      item, except bodily pain, is lower in both group of patients in comparison with
      controls. Pearson correlation analysis shows negative correlations on HRQOL of
      depression, SOM and anxiety both in cirrhotic and HCC subjects, also of obsessive
      compulsive and hostility items in HCC. This is the first report on the
      psychopathological profile of HCC patients: the results open questions on the
      role of psychological interventions that may improve HRQOL of patients before
      treatment and in the follow-up.

PMID- 24323277
TI  - Bench to cribside: the path for developing a neuroprotectant.
AB  - The consequences of perinatal brain injury include immeasurable anguish for
      families and substantial ongoing costs for care and support of effected children.
      Factors associated with perinatal brain injury in the preterm infant include
      inflammation and infection, and with increasing gestational age, a higher
      proportion is related to hypoxic-ischemic events, such as stroke and placental
      abruption. Over the past decade, we have acquired new insights in the mechanisms
      underpinning injury and many new tools to monitor outcome in perinatal brain
      injury in our experimental models. By embracing these new technologies, we can
      expedite the screening of novel therapies. This is critical as despite enormous
      efforts of the research community, hypothermia is the only viable
      neurotherapeutic, and this procedure is limited to term birth and postcardiac
      arrest hypoxic-ischemic events. Importantly, experimental and preliminary data in
      humans also indicate a considerable therapeutic potential for melatonin against
      perinatal brain injury. However, even if this suggested potential is proven, the
      complexity of the human condition means we are likely to need additional
      neuroprotective and regenerative strategies. Thus, within this review, we will
      outline what we consider the key stages of preclinical testing and development
      for a neuroprotectant or regenerative neurotherapy for perinatal brain injury. We
      will also highlight examples of novel small animal physiological and behavioral
      testing that gives small animal preclinical models greater clinical relevance. We
      hope these new tools and an integrated bench to cribside strategic plan will
      facilitate the fulfillment of our overarching goal, improving the long-term brain
      health and quality of life for infants suffering perinatal brain injury. 

PMID- 24323279
TI  - Salivary markers of oxidative stress in patients with obstructive sleep apnea
      treated with continuous positive airway pressure.
AB  - PURPOSE: Obstructive sleep apnea syndrome (OSAS) is characterized by elevated
      oxidative stress. Measurement of oxidative stress in saliva seems to be promising
      in long-term treatment monitoring of OSAS patients. In this study, our aim was to
      investigate whether short-term continuous positive airway pressure (CPAP)
      treatment would influence oxidative stress in saliva. METHODS: Patients with
      diagnosed OSAS (16 women, 28 men) underwent polysomnography during the first
      night and CPAP treatment during the second night. Saliva samples were taken in
      the evening and morning on both days. Markers of oxidative stress and antioxidant
      status were analyzed in saliva. RESULTS: Evening concentrations of the salivary
      thiobarbituric acid reacting substances (p < 0.001), advanced glycation end
      products (p < 0.001), and advanced oxidation protein products (p < 0.01) were
      significantly lower than morning values during the diagnostic night. However,
      salivary concentrations of none of the oxidative stress markers were
      significantly influenced by the CPAP treatment. No changes in salivary
      antioxidant status after CPAP therapy were found. CONCLUSION: Salivary markers of
      oxidative stress and antioxidant status do not change significantly after one
      night treatment with CPAP. On the contrary, after 1 month with CPAP therapy,
      reduced markers of oxidative stress were reported. Therefore, the future studies
      should be focused on finding the optimal sampling frequency to clarify the
      potential of saliva for the monitoring of OSAS treatment.

PMID- 24323280
TI  - Newborns, one of the last therapeutic orphans to be adopted.

PMID- 24323284
TI  - Revisiting the fundamental physical chemistry in heterogeneous photocatalysis:
      its thermodynamics and kinetics.
AB  - Although the history of photocatalysis research is not so long, many researchers
      have studied photocatalysis and a large number of papers on photocatalysis have
      been published. The objectives of this review paper are to revisit the
      fundamentals of photocatalysis, especially its thermodynamics and kinetics, which
      have not been reexamined in recent studies, to clarify the problems, if any, that
      prevent developments in the field of photocatalysis, and to present insights for
      future progress. 

PMID- 24323283
TI  - Evaluating self-management behaviors of diabetic patients in a telehealthcare
      program: longitudinal study over 18 months.
AB  - BACKGROUND: Self-management is an important skill for patients with diabetes, and
      it involves frequent monitoring of glucose levels and behavior modification.
      Techniques to enhance the behavior changes of diabetic patients have been
      developed, such as diabetes self-management education and telehealthcare.
      Although the patients are engaged in self-management activities, barriers to
      behavior changes remain and additional work is necessary to address the impact of
      electronic media and telehealthcare on patient self-care behaviors. OBJECTIVE:
      The aims of this study were to (1) explore the behaviors of diabetic patients
      interacting with online applications, (2) determine the impact of a
      telehealthcare program among 7 self-care behaviors of the patients, and (3)
      determine the changes in glycosylated hemoglobin (HbA1c) levels. METHODS: A
      telehealthcare program was conducted to assist the patients with 7 self-care
      activities. The telehealthcare program lasted for 18 months and included the use
      of a third-generation mobile telecommunications glucometer, an online diabetes
      self-management system, and a teleconsultant service. We analyzed the data of 59
      patients who participated in the telehealthcare program and 103 who did not. The
      behavioral assessments and the HbA1c data were collected and statistically
      analyzed to determine whether the telehealthcare services had an impact on the
      patients. We divided the 18-month period into 3 6-month intervals and analyzed
      the parameters of patients assisted by the telehealthcare service at different
      time points. We also compared the results of those who were assisted by the
      telehealthcare service with those who were not. RESULTS: There was a significant
      difference in monitoring blood glucose between the beginning and the end of the
      patient participation (P=.046) and between the overall period and the end of
      patient participation (P<.001). Five behaviors were significantly different
      between the intervention and control patients: being active (P<.001), healthy
      eating (P<.001), taking medication (P<.001), healthy coping (P=.02), and problem
      solving (P<.001). Monitoring of blood glucose was significantly different (P=.02)
      during the 6-12 month stage of patient participation between the intervention and
      control patients. A significant difference between the beginning and the 6-12
      month stage of patient participation was observed for the mean value of HbA1c
      level (P=.02), and the differences between the overall HbA1c variability and the
      variability of each 6-month interval was also significant. CONCLUSIONS:
      Telehealthcare had a positive effect on diabetic patients. This study had
      enhanced blood glucose monitoring, and the patients in the program showed
      improvements in glycemic control. The self-care behaviors affect patient
      outcomes, and the changes of behavior require time to show the effects.

PMID- 24323285
TI  - Activating C4-dicarboxylate transporters DcuB and DcuC for improving succinate
      production.
AB  - Although many efforts had been performed to engineer Escherichia coli for
      succinate production, succinate efflux system had not been investigated as an
      engineering target for improving succinate production. In this work, four Dcu
      transporters, which had been reported to be responsible for C4-dicarboxylates
      transportation of E. coli, were investigated for their succinate efflux
      capabilities. These four dcu genes were deleted individually in a previously
      constructed succinate-producing strain to study their effects on succinate
      production. Deleting dcuA and dcuD genes had nearly no influence, while deleting
      dcuB and dcuC genes led to 15 and 11% decrease of succinate titer, respectively.
      Deleting both dcuB and dcuC genes resulted in 90% decrease of succinate titer,
      suggesting that DcuB and DcuC were the main transporters for succinate efflux and
      they functioned as independent and mutually redundant succinate efflux
      transporters. Furthermore, RBS library having strengths varied from 0.17 to 8.6
      times of induced E. coli lacZ promoter was used to modulate dcuB and dcuC genes
      for improving succinate production. Modulating these two genes in combination led
      to 34% increase of succinate titer. To the best of knowledge, this was the first
      report about improving succinate production through engineering succinate efflux
      system.

PMID- 24323286
TI  - Growth of the extremophilic Deinococcus geothermalis DSM 11302 using co-substrate
      fed-batch culture.
AB  - Deinococcus geothermalis metabolism has been scarcely studied to date, although
      new developments on its utilization for bioremediation have been carried out. So,
      large-scale production of this strain and a better understanding of its
      physiology are required. A fed-batch experiment was conducted to achieve a high
      cell density non-limiting culture of D. geothermalis DSM 11302. A co-substrate
      nutritional strategy using glucose and yeast extract was carried out in a 20-L
      bioreactor in order to maintain a non-limited growth at a maximal growth rate of
      1 h(-1) at 45  degrees C. Substrate supplies were adjusted by monitoring online
      culture parameters and physiological data (dissolved oxygen, gas analyses,
      respiratory quotient, biomass concentration). The results showed that yeast
      extract could serve as both carbon and nitrogen sources, although glucose and
      ammonia were consumed too. Yeast extract carbon-specific uptake rate reached a
      value 4.5 times higher than glucose carbon-specific uptake rate. Cell
      concentration of 9.6 g L(-1) dry cell weight corresponding to 99 g of biomass was
      obtained using glucose and yeast extract as carbon and nitrogen sources.

PMID- 24323281
TI  - Wnt signaling and the control of human stem cell fate.
AB  - Wnt signaling determines major developmental processes in the embryonic state and
      regulates maintenance, self-renewal and differentiation of adult mammalian tissue
      stem cells. Both beta-catenin dependent and independent Wnt pathways exist, and
      both affect stem cell fate in developing and adult tissues. In this review, we
      debate the response to Wnt signal activation in embryonic stem cells and human,
      adult stem cells of mesenchymal, hematopoetic, intestinal, gastric, epidermal,
      mammary and neural lineages, and discuss the need for Wnt signaling in these cell
      types. Due to the vital actions of Wnt signaling in developmental and maintenance
      processes, deregulation of the pathway can culminate into a broad spectrum of
      developmental and genetic diseases, including cancer. The way in which Wnt
      signals can feed tumors and maintain cancer stem stells is discussed as well.
      Manipulation of Wnt signals both in vivo and in vitro thus carries potential for
      therapeutic approaches such as tissue engineering for regenerative medicine and
      anti-cancer treatment. Although many questions remain regarding the complete Wnt
      signal cell-type specific response and interplay of Wnt signaling with pathways
      such as BMP, Hedgehog and Notch, we hereby provide an overview of current
      knowledge on Wnt signaling and its control over human stem cell fate. 

PMID- 24323287
TI  - Holomycin, a dithiolopyrrolone compound produced by Streptomyces clavuligerus.
AB  - Holomycin is a member of the dithiolopyrrolone class of secondary metabolites. It
      contains a cromophore formed by two heterocycles, one of them carrying a
      disulfide bridge. The holomycin chromophore is also present in thioluthin,
      aureothricin, the xenorhabdins and the complex thiomarinols. Streptomyces
      clavuligerus ATCC 27064 contains the holomycin gene cluster (hlm). This
      antibiotic is formed by a cysteine-activating non-ribosomal peptide synthetase
      followed by four reduction steps by a set of four different flavoproteins; the
      intermediate is cyclized by a thiol oxidase and modified by acylation. Holomycin
      is a broad spectrum antibiotic, reported as antitumoral, acting in vivo on RNA
      synthesis. It is modified intracellularly by the producer strains by methylation
      and formation of heterodimers as a way of self-protection. Holomycin might be a
      lead molecule for the production of new hybrid compounds with higher activity and
      lower toxicity. 

PMID- 24323288
TI  - 2,3-butanediol production from starch by engineered Klebsiella pneumoniae G31-A.
AB  - 2,3-Butanediol (2,3-BD) is an organic compound, which is widely used as a fuel
      and fuel additive and applied in chemical, food, and pharmaceutical industries.
      Contemporary strategies for its economic synthesis include the development of
      microbial technologies that use starch as cheap and renewable feedstock. The
      present work encompasses the metabolic engineering of the excellent 2,3-BD
      producer Klebsiella pneumoniae G31. In order to perform direct starch conversion
      into 2,3-BD, the amyL gene encoding quite active, liquefying alpha-amylase in
      Bacillus licheniformis was cloned under lac promoter control in the recombinant
      K. pneumoniae G31-A. The enhanced extracellular over-expression of amyL led to
      the highest extracellular amylase activity (68 U/ml) ever detected in Klebsiella.
      The recombinant strain was capable of simultaneous saccharification and
      fermentation (SSF) of potato starch to 2,3-BD. In SSF batch process by the use of
      200 g/l starch, the amount of total diols produced was 60.9 g/l (53.8 g/l 2,3-BD
      and 7.1 g/l acetoin), corresponding to 0.31 g/g conversion rate. The presented
      results are the first to show successful starch conversion to 2,3-BD by K.
      pneumoniae in a one-step process.

PMID- 24323289
TI  - Screening a random mutagenesis library of a fungal beta-fructofuranosidase using
      FT-MIR ATR spectroscopy and multivariate analysis.
AB  - Short-chain fructooligosaccharides (scFOS) are valuable health-promoting food
      additives. During the batch production of scFOS from sucrose the beta
      fructofuranosidase catalyst is subject to product inhibition by glucose.
      Engineering the enzyme for reduced sensitivity to glucose could improve product
      yields or process productivity while preserving the simple industrial batch
      design. Random mutagenesis is a useful technique for engineering proteins but
      should be coupled to a relevant high-throughput screen. Such a screen for sucrose
      and scFOS quantification remains elusive. This work presents the development of a
      screening method displaying potential high-throughput capacity for the evaluation
      of beta-fructofuranosidase libraries using Fourier transform mid-infrared
      attenuated total reflectance (FT-MIR ATR) spectroscopy and multivariate analysis.
      A calibration model for the quantification of sucrose in enzyme assay samples
      ranged from 5 to 200 g/l and the standard error of prediction was below 13 g/l. A
      library of the Aspergillus japonicus fopA gene was generated by error prone PCR
      and screened in Saccharomyces cerevisiae. Using FT-MIR ATR spectroscopy,
      potential hits were identified as those variants that converted more sucrose in
      the presence of the glucose inhibitor than the parent. Subsequent analysis of
      reaction products generated by top performers using high-performance liquid
      chromatography identified a variant producing higher scFOS levels than the
      parent. At the peak difference in performance the variant produced 28 % more
      scFOS from the same amount of sucrose. This study highlights the application of
      FT-MIR ATR spectroscopy to a variant discovery pipeline in the directed evolution
      of a beta-fructofuranosidase for enhanced scFOS production. 

PMID- 24323290
TI  - Malate synthase gene AoMls in the nematode-trapping fungus Arthrobotrys
      oligospora contributes to conidiation, trap formation, and pathogenicity.
AB  - Malate synthase (Mls), a key enzyme in the glyoxylate cycle, is required for
      virulence in microbial pathogens. In this study, we identified the AoMls gene
      from the nematode-trapping fungus Arthobotrys oligospora. The gene contains 4
      introns and encodes a polypeptide of 540 amino acids. To characterize the
      function of AoMls in A. oligospora, we disrupted it by homologous recombination,
      and the DeltaAoMls mutants were confirmed by PCR and Southern blot analyses. The
      growth rate and colony morphology of the DeltaAoMls mutants showed no obvious
      difference from the wild-type strains on potato dextrose agar (PDA) plate.
      However, the disruption of gene AoMls led to a significant reduction in
      conidiation, failure to utilize fatty acids and sodium acetate for growth, and
      its conidia were unable to germinate on minimal medium supplemented with sodium
      oleate. In addition, the trap formation was retarded in the DeltaAoMls mutants,
      which only produced immature traps containing one or two rings. Moreover, the
      nematicidal activity of the DeltaAoMls mutants was significantly decreased. Our
      results suggest that the gene AoMls plays an important role in conidiation, trap
      formation and pathogenicity of A. oligospora.

PMID- 24323291
TI  - Protein tyrosine kinase 6 regulates mammary gland tumorigenesis in mouse models.
AB  - Protein tyrosine kinase 6 (PTK6, also called BRK) is an intracellular tyrosine
      kinase expressed in the majority of human breast tumors and breast cancer cell
      lines, but its expression has not been reported in normal mammary gland. To study
      functions of PTK6 in vivo, we generated and characterized several transgenic
      mouse lines with expression of human PTK6 under control of the mouse mammary
      tumor virus (MMTV) long terminal repeat. Ectopic active PTK6 was detected in
      luminal epithelial cells of mature transgenic mammary glands. Lines expressing
      the MMTV-PTK6 transgene exhibited more than a two-fold increase in mammary gland
      tumor formation compared with nontransgenic control animals. PTK6 activates
      signal transducer and activator of transcription 3 (STAT3), and active STAT3 was
      detected in PTK6-positive mammary gland epithelial cells. Endogenous mouse PTK6
      was not detected in the normal mouse mammary gland, but it was induced in mouse
      mammary gland tumors of different origin, including spontaneous tumors that
      developed in control mice, and tumors that formed in PTK6, H-Ras, ERBB2 and PyMT
      transgenic models. MMTV-PTK6 and MMTV-ERBB2 transgenic mice were crossed to
      explore crosstalk between PTK6 and ERBB2 signaling in vivo. We found no
      significant increase in tumor incidence, size or metastasis in ERBB2/PTK6 double
      transgenic mice. Although we detected increased proliferation in ERBB2/PTK6
      double transgenic tumors, an increase in apoptosis was also observed. MMTV-PTK6
      clearly promotes mammary gland tumorigenesis in vivo, but its impact may be
      underrepresented in our transgenic models because of induction of endogenous PTK6
      expression. 

PMID- 24323292
TI  - Acceleration forces can effect cardiovascular structure.

PMID- 24323293
TI  - Chiral Bronsted acid-catalyzed enantioselective addition of indoles to ketimines.
AB  - A highly enantioselective addition of indoles to a readily available ketimine was
      found to be catalyzed by a chiral phosphoric acid. This organocatalytic process
      represents a rare example of an addition reaction to a non-aromatic ketimine. 

PMID- 24323295
TI  - In situ growth of Au nanocrystals on graphene oxide sheets.
AB  - Au nanocrystals (AuNCs) with a size of 10-20 nm decorated on graphene oxide (GO)
      were fabricated successfully through a hydrothermal reduction and crystallization
      route without any extra reductants and capping agents. The hydrophobic areas of
      GO benefit the formation of nanocrystals (NCs) with {111} facets totally exposed;
      however, the hydrophilic areas are detrimental to the crystallization. The
      morphology of AuNCs could be tailored by the degree of oxidation on the GO
      surface. The shape-controllable and reducing properties of GO are in favor of
      "clean" synthesis of noble metal NCs decorated on graphene. 

PMID- 24323296
TI  - Potential role of repetitive transcranial magnetic stimulation in obesity.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive
      technique with mild side effects. Some forms of obesity may arise from eating
      disorders and recent data suggest that rTMS treatment could have beneficial
      effects in eating disorders. PURPOSE: The purpose of this comprehensive review is
      to hypothesize that rTMS may play a role in obesity. MATERIALS AND METHODS:
      Articles were selected based on a search on medline using the terms "rTMS", "food
      craving", "eating disorders", "addiction", and "obesity". They were published
      between 1995 and 2013. RESULTS: Repetitive transcranial magnetic stimulation has
      been evaluated in the treatment of bulimia nervosa. It appears that it exerts its
      effect via the reduction of the level of craving for food. Obesity is being
      recognized as one of the endpoints of food addiction and craving. Besides, rTMS
      and transcranial direct current stimulation are brain stimulation techniques
      being used in the treatment of psychoactive substance addiction. CONCLUSIONS:
      Repetitive transcranial magnetic stimulation, through the reduction of food
      craving may be a potential treatment for a subset of individuals suffering from
      obesity. Further studies with a higher number of subjects are still needed to
      confirm the effects of rTMS on obesity.

PMID- 24323297
TI  - Does standard deviation matter? Using "standard deviation" to quantify security
      of multistage testing.
AB  - With the advent of web-based technology, online testing is becoming a mainstream
      mode in large-scale educational assessments. Most online tests are administered
      continuously in a testing window, which may post test security problems because
      examinees who take the test earlier may share information with those who take the
      test later. Researchers have proposed various statistical indices to assess the
      test security, and one most often used index is the average test-overlap rate,
      which was further generalized to the item pooling index (Chang & Zhang, 2002,
      2003). These indices, however, are all defined as the means (that is, the
      expected proportion of common items among examinees) and they were originally
      proposed for computerized adaptive testing (CAT). Recently, multistage testing
      (MST) has become a popular alternative to CAT. The unique features of MST make it
      important to report not only the mean, but also the standard deviation (SD) of
      test overlap rate, as we advocate in this paper. The standard deviation of test
      overlap rate adds important information to the test security profile, because for
      the same mean, a large SD reflects that certain groups of examinees share more
      common items than other groups. In this study, we analytically derived the lower
      bounds of the SD under MST, with the results under CAT as a benchmark. It is
      shown that when the mean overlap rate is the same between MST and CAT, the SD of
      test overlap tends to be larger in MST. A simulation study was conducted to
      provide empirical evidence. We also compared the security of MST under the single
      pool versus the multiple-pool designs; both analytical and simulation studies
      show that the non-overlapping multiple-pool design will slightly increase the
      security risk.

PMID- 24323294
TI  - Gene-environment interactions in common mental disorders: an update and strategy
      for a genome-wide search.
AB  - A decade of research has demonstrated the explanatory potential of interplay
      between genetic variants and environmental factors in the development of common
      mental disorders. Initial findings have undergone tests of replicability and
      specificity. Some gene-environment interactions have been confirmed, some have
      not replicated and yet other turned out to be more specific than initially
      thought. Specific and complementary roles of genetic factors have been
      delineated: a common functional length polymorphism in the serotonin transporter
      gene (5-HTTLPR) moderated the effect of childhood maltreatment on chronic
      depression in adulthood, but did not substantially influence the effects of adult
      stressful life events on the onset of new depressive episodes; in contrast, a
      common functional polymorphism in the brain-derived neurotrophic factor gene
      (BDNF) moderated the effect of stressful life events in adulthood in triggering
      new depressive episodes, but did not influence the effects of childhood
      maltreatment. Molecular mechanisms underlying gene-environment interactions are
      being uncovered, including DNA methylation and other epigenetic modifications.
      New gene-environment interactions continue to be reported, still largely from
      hypothesis-driven research. Statistical and biological prioritization strategies
      are proposed to facilitate a systematic discovery of novel gene-environment
      interactions in genome-wide analyses. 

PMID- 24323298
TI  - Spontaneous onset of complex regional pain syndrome Type I in a woman infected
      with Bartonella koehlerae.
AB  - After a short-term fever, complex regional pain syndrome, characterized by
      hyperalgesia, intermittent swelling, erythema and cyanosis of both feet, was
      diagnosed in a female veterinarian. The woman was infected with Bartonella
      koehlerae and she was also Bartonella vinsonii subsp. berkhoffii seroreactive.
      Having failed other treatments, symptoms resolved following initiation of
      antibiotics. 

PMID- 24323300
TI  - Distal occlusion of the middle cerebral artery in mice: are we ready to assess
      long-term functional outcome?
AB  - Rodent animal models of stroke are widely used with brain ischemia inducible by
      various occlusion methods. Permanent or transient occlusion of the distal portion
      of the middle cerebral artery (MCAO) offers a reproducible model with low
      mortality rates, and it is the most likely model of choice for mid- and long-term
      studies to assess neurorepair or long-term effects of neuroprotective drugs.
      Therefore, a measurable and stable neurological assessment would be required to
      evaluate sensorimotor and cognitive deficits at short and long terms as suggested
      by the Stroke Therapy Academic Industry Roundtable preclinical recommendations.
      We review the usefulness of different tests used to measure functional outcome
      after distal MCAO in mice and further sustain these data with our own
      multilaboratories' experience. Results show that several tests were suitable to
      detect neurological deterioration at short term. Grip strength and latency to
      move have shown some usefulness at long term, with important differences between
      strains, while less clear are the data for the corner test. Important strain
      differences in terms of infarct volume are also reported in this study.
      Statistical power analysis and sample size calculation of our data confirmed the
      value of grip strength and latency to move tests but suggest that larger sample
      size would be required. In conclusion, there are no robust data supporting the
      use of a specific behavior test to assess long-term functional outcome after
      distal MCAO in mice. This is an important limitation since translational basic
      research should provide data to help further clinical trial evaluation. New
      multicenter studies with larger sample size and specific mouse strains are needed
      to confirm the validity of tests, such as the corner, latency to move or grip
      strength. 

PMID- 24323299
TI  - SAHIT Investigators--on the outcome of some subarachnoid hemorrhage clinical
      trials.
AB  - Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved
      over the last decades. Yet, case fatality remains nearly 40% and survivors often
      have permanent neurological, cognitive and/or behavioural sequelae. Other than
      nimodipine drug or clinical trials have not consistently improved outcome. We
      formed a collaboration of SAH investigators to create a resource for prognostic
      analysis and for studies aimed at optimizing the design and analysis of phase 3
      trials in aneurysmal SAH. We identified investigators with data from randomized,
      clinical trials of patients with aneurysmal SAH or prospectively collected single
      or multicentre databases of aneurysmal SAH patients. Data are being collected
      and proposals to use the data and to design future phase 3 clinical trials are
      being discussed. This paper reviews some issues discussed at the first meeting of
      the SAH international trialists (SAHIT) repository meeting. Investigators
      contributed or have agreed to contribute data from several phase 3 trials
      including the tirilazad trials, intraoperative hypothermia for aneurysmal SAH
      trial, nicardipine clinical trials, international subarachnoid aneurysm trial,
      intravenous magnesium sulphate for aneurysmal SAH, magnesium for aneurysmal SAH
      and from prospectively-collected data from four institutions. The number of
      patients should reach 15,000. Some industry investigators refused to provide data
      and others reported that their institutional research ethics boards would not
      permit even deidentified or anonymized data to be included. Others reported
      conflict of interest that prevented them from submitting data. The problems with
      merging data were related to lack of common definitions and coding of variables,
      differences in outcome scales used, and times of assessment. Some questions for
      investigation that arose are discussed. SAHIT demonstrates the possibility of SAH
      investigators to contribute data for collaborative research. The problems are
      similar to those already documented in other similar collaborative efforts such
      as in head injury research. We encourage clinical trial and registry
      investigators to contact us and participate in SAHIT. Key issues moving forward
      will be to use common definitions (common data elements), outcomes analysis, and
      to prioritize research questions, among others.

PMID- 24323301
TI  - Guidelines for using mouse global cerebral ischemia models.
AB  - Mouse models of global cerebral ischemia are essential tools to study the
      molecular mechanisms involved in ischemic brain damage. The availability of
      genetically engineered mice allows examination of the role of specific proteins
      in brain pathology processes. However, relative to rat models, mouse global brain
      ischemia models are technically more challenging to produce. It is important to
      emphasize that occlusion of two carotid arteries only is highly inefficient to
      produce consistent brain damage in mice. This is mainly due to high variability
      in their vascular anatomy. Several approaches were developed to achieve
      sufficient reduction of blood flow in the mouse brain that led to consistent
      ischemic brain damage. We describe here the mouse ischemic models most frequently
      utilized in research laboratories to test the effect of genetically manipulated
      proteins of interest on ischemic brain injury or to assess a drug effect on
      ischemia-induced brain damage. The most common approach used is the bilateral
      common carotid occlusion that is combined with either occlusion of a third artery
      or with concomitant reduction of mean arterial blood pressure. Furthermore, a
      four-vessel occlusion model can be used or even a cardiac arrest model that has
      been developed for mouse. All these models have specific problems, advantages,
      and clinical relevance. Thus, the feasibility of using a particular model depends
      on the goal of the study and the outcome parameters assessed. Overall, the mouse
      models are valuable since they allow the study of ischemia-induced molecular
      mechanisms utilizing transgenic animals and also evaluate the effect of new
      neuroprotective compounds. 

PMID- 24323302
TI  - Characterisation of endothelin-1-induced intrastriatal lesions within the
      juvenile and adult rat brain using MRI and 31P MRS.
AB  - Improved non-invasive magnetic resonance (MR) characterisation of in vivo models
      of focal ischaemic insults such as transient ischaemic attack (TIA) and perinatal
      arterial ischaemic stroke (AIS) may assist diagnosis, outcome prediction and
      treatment design. The classic middle cerebral artery occlusion (MCAO) model of
      ischaemic stroke is well documented in MR studies but generates extensive and
      complex lesions involving an acute inflammatory response and de-occlusion that
      immediately restores circulation. By contrast, intrastriatal microinjection of
      the potent vasoconstrictor, endothelin-1 (ET-1), induces a focal, reversible and
      low-flow ischaemia in the absence of a typical inflammatory response, which
      gradually restores blood flow over several hours and may be more relevant to TIA
      and AIS pathology. This study presents the first comprehensive longitudinal MR
      characterisation of the real-time anatomical [T1-weighted (T1-w)/T2-weighted (T2
      w)], pathophysiological [apparent diffusion coefficient (ADC), cerebral blood
      volume, gadolinium contrast imaging of blood-brain barrier (BBB) integrity] and
      metabolic [phosphorus magnetic resonance spectroscopy (31P MRS)] evolution of a
      purely ischaemic ET-1-induced lesion within the juvenile and adult rat brain. ET
      1-induced cytotoxic oedema was visualised on T2-w magnetic resonance imaging
      (MRI), inconsistent with the conventional notion that it cannot be detected using
      anatomical MRI. There was no immunohistochemical evidence of an acute
      inflammatory response or loss of BBB integrity, thus excluding a vasogenic oedema
      contribution to the pathology. Maximal T2-w intensity correlated with the lowest
      ADC value in both age groups, re-emphasising the purely ischaemic nature of the
      lesion and the absence of vasogenic oedema. Furthermore, extensive acute T1-w
      hypointensity was observed in the presence of cytotoxic oedema-induced T2-w
      changes, whereas other authors have shown that increased T1 values following MCAO
      reflect vasogenic oedema. Intriguingly, the lesion border exhibited
      hyperintensity on T2-w and ADC MRI at later time points, and the former may be a
      consequence of phagocytosis-induced fatty droplet deposition by macrophages
      detected immunohistochemically. In spite of a chronically reduced ADC, typically
      associated with ischaemia-induced energy failure, a 31P MRS-detectable reduction
      in the phosphocreatine (PCr) to gamma adenosine triphosphate (gammaATP) ratio was
      not observed at any time point in either age group, suggesting dissociation of
      tissue water diffusion and metabolic changes within the ET-1-induced lesion.

PMID- 24323303
TI  - Polymorphisms in ACVRL1 and endoglin genes are not associated with sporadic and
      HHT-related brain AVMs in Dutch patients.
AB  - We aimed to replicate the association of the IVS3-35A>G polymorphism in the
      activin receptor-like kinase (ACVRL) 1 gene and the 207G>A polymorphism in the
      endoglin (ENG) gene with sporadic brain arteriovenous malformations (BAVM) in
      Dutch BAVM patients. In addition, we assessed whether these polymorphisms
      contribute to the risk of BAVM in patients with hereditary haemorrhagic
      telangiectasia type 1 (HHT1). We genotyped 143 Dutch sporadic BAVM patients and
      360 healthy volunteers for four variants in the ACVRL1 gene including IVS3-35A>G
      and two variants in the ENG gene including 207G>A. Differences in allele and
      genotype frequencies between sporadic BAVM patients and controls and their
      combined effect were analysed with a likelihood ratio test. Furthermore, we
      compared the allele and genotype frequencies between 24 HHT1 patients with a BAVM
      with those of a relative with HHT1 without a BAVM in a matched pair analysis
      using Wilcoxon signed rank test. No significant differences in allele frequency
      were found between sporadic BAVM cases and controls or between HHT1 patients with
      and without BAVM for any of the polymorphisms or the combination of ACVRL1 and
      ENG polymorphisms. Meta-analysis of the current and the two previous studies for
      the ACVRL1 IVS3-35A polymorphism showed a persisting association between the
      ACVRL1 IVS3-35A polymorphism and risk of sporadic BAVM (odds ratio, 1.86; 95% CI:
      1.32-2.61, p<0.001). We did not replicate the previously found association
      between a polymorphism in ACVRL1 IVS3-35A>G and BAVM in Dutch patients. However,
      meta-analysis did not rule out a possible effect.

PMID- 24323304
TI  - Design and self-assembly of variform organometallic macrocycle with terminal
      imidazole-based bridging ligands utilizing joints twist and rotation.
AB  - Organometallic macrocycles based on bridge ligands with terminal imidazole groups
      show the formation of various patterns. The end imidazolyl finishes the
      conjugated system on the back bone and can freely twist or rotate just like the
      joints of a human body such as the knee and wrist. 

PMID- 24323305
TI  - The Filament Editor: an interactive software environment for visualization, proof
      editing and analysis of 3D neuron morphology.
AB  - Neuroanatomical analysis, such as classification of cell types, depends on
      reliable reconstruction of large numbers of complete 3D dendrite and axon
      morphologies. At present, the majority of neuron reconstructions are obtained
      from preparations in a single tissue slice in vitro, thus suffering from cut off
      dendrites and, more dramatically, cut off axons. In general, axons can innervate
      volumes of several cubic millimeters and may reach path lengths of tens of
      centimeters. Thus, their complete reconstruction requires in vivo labeling,
      histological sectioning and imaging of large fields of view. Unfortunately,
      anisotropic background conditions across such large tissue volumes, as well as
      faintly labeled thin neurites, result in incomplete or erroneous automated
      tracings and even lead experts to make annotation errors during manual
      reconstructions. Consequently, tracing reliability renders the major bottleneck
      for reconstructing complete 3D neuron morphologies. Here, we present a novel set
      of tools, integrated into a software environment named 'Filament Editor', for
      creating reliable neuron tracings from sparsely labeled in vivo datasets. The
      Filament Editor allows for simultaneous visualization of complex neuronal
      tracings and image data in a 3D viewer, proof-editing of neuronal tracings,
      alignment and interconnection across sections, and morphometric analysis in
      relation to 3D anatomical reference structures. We illustrate the functionality
      of the Filament Editor on the example of in vivo labeled axons and demonstrate
      that for the exemplary dataset the final tracing results after proof-editing are
      independent of the expertise of the human operator. 

PMID- 24323306
TI  - Normal cerebral FDG uptake during childhood.
AB  - PURPOSE: Current understanding of cerebral FDG uptake during childhood originates
      from a small number of studies in patients with neurological abnormalities. Our
      aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children
      more likely to represent a normal population. METHODS: We reviewed cerebral FDG
      PET scans in children up to 16 years of age with suspected/proven extracranial
      malignancies and the following exclusions: central nervous system metastases,
      previous malignancies, previous chemotherapy or radiotherapy, development of
      cerebral metastases during therapy, neurological conditions, taking antiepileptic
      medication or medications likely to interfere with cerebral metabolism, and
      general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the
      cerebellar cortex were analysed using regional SUV(max), and the cerebral cortex,
      basal ganglia, thalamus and cerebellum were analysed using a regional relative
      uptake analysis in comparison to maximal cortical uptake. RESULTS: Scans from 30
      patients (age range 11 months to 16 years, mean age 10 years 5 months) were
      included. All regions showed increasing SUV(max) with age. The parietal,
      occipital, lateral temporal and medial temporal lobes showed lower rates of
      increasing FDG uptake causing changing patterns of regional FDG uptake during
      childhood. The cortical regions showing the most intense uptake in early
      childhood were the parietal and occipital lobes. At approximately 7 years of age
      these regions had relatively less uptake than the frontal lobes and at
      approximately 10 years of age these regions had relatively less uptake than the
      thalamus. CONCLUSION: Relative FDG uptake in the brain has not reached an adult
      pattern by 1 year of age, but continues to change up to 16 years of age. The
      changing pattern is due to different regional rates of increasing cortical FDG
      uptake, which is less rapid in the parietal, occipital and temporal lobes than in
      the frontal lobes.

PMID- 24323307
TI  - Genetic variation and population genetic structure of Rhizophora apiculata
      (Rhizophoraceae) in the Greater Sunda Islands, Indonesia using microsatellite
      markers.
AB  - Genetic variations within and among Rhizophora apiculata populations in the
      Greater Sunda Islands of Indonesia were studied using microsatellite markers. The
      study found 38 alleles on five loci in 15 populations. The observed (H(o)) and
      expected (H(e)) heterozygosity values are 0.338 and 0.378, respectively.
      Inbreeding effect from self-pollination might explain its heterozygote
      deficiency. Population genetic differentiation (F(ST) = 0.381) was similar to
      other mangrove species. The genetic diversity of R. apiculata populations along
      the coastline inside the archipelago (e.g., Buleleng, Donggala, Mamuju, and
      Takalar) was higher than those of population along the coastline outside the
      archipelago, especially northern Sumatra populations (i.e., Langkat, Tapanuli
      Tengah, Dumai, and Padang). The isolation by distances and sea currents
      directions as well as their connectivity might affect the gene flow and genetic
      exchange. The more isolated with fewer connections by sea currents, the smaller
      gene flow and genetic exchange observed between populations. The higher genetic
      exchange, on the contrary, occurred when population location was closer to the
      meeting point of the sea currents. The study also showed that the patterns of sea
      current movement seemed to have influence genetic clustering of populations which
      fell into three main groups (Sunda Shelf Mangroves) and one isolated population
      (New Guinea Mangroves).

PMID- 24323308
TI  - Larvivorous fish for preventing malaria transmission.
AB  - BACKGROUND: Adult anopheline mosquitoes transmit Plasmodium parasites that cause
      malaria. Some fish species eat mosquito larvae and pupae. In disease control
      policy documents, the World Health Organization includes biological control of
      malaria vectors by stocking ponds, rivers, and water collections near where
      people live with larvivorous fish to reduce Plasmodium parasite transmission. The
      Global Fund finances larvivorous fish programmes in some countries, and, with
      increasing efforts in eradication of malaria, policy makers may return to this
      option. We therefore assessed the evidence base for larvivorous fish programmes
      in malaria control. OBJECTIVES: Our main objective was to evaluate whether
      introducing larvivorous fish to anopheline breeding sites impacts Plasmodium
      parasite transmission. Our secondary objective was to summarize studies
      evaluating whether introducing larvivorous fish influences the density and
      presence of Anopheles larvae and pupae in water sources, to understand whether
      fish can possibly have an effect. SEARCH METHODS: We attempted to identify all
      relevant studies regardless of language or publication status (published,
      unpublished, in press, or ongoing). We searched the following databases: the
      Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central
      Register of Controlled Trials (CENTRAL), published in The Cochrane Library;
      MEDLINE; EMBASE; CABS Abstracts; LILACS; and the metaRegister of Controlled
      Trials (mRCT) until 18 June 2013. We checked the reference lists of all studies
      identified by the above methods. We also examined references listed in review
      articles and previously compiled bibliographies to look for eligible studies.
      SELECTION CRITERIA: Randomized controlled trials and non-randomized controlled
      trials, including controlled before-and-after studies, controlled time series and
      controlled interrupted time series studies from malaria-endemic regions that
      introduced fish as a larvicide and reported on malaria in the community or the
      density of the adult anopheline population. In the absence of direct evidence of
      an effect on transmission, we carried out a secondary analysis on studies that
      evaluated the effect of introducing larvivorous fish on the density or presence
      of immature anopheline mosquitoes (larvae and pupae forms) in community water
      sources to determine whether this intervention has any potential in further
      research on control of malaria vectors. DATA COLLECTION AND ANALYSIS: Three
      review authors screened abstracts and examined potentially relevant studies by
      using an eligibility form. Two review authors independently extracted data and
      assessed risk of bias of included studies. If relevant data were unclear or were
      not reported, we wrote to the trial authors for clarification. We presented data
      in tables, and we summarized studies that evaluated the effects of fish
      introduction on anopheline immature density or presence, or both. We used GRADE
      to summarize evidence quality. We also examined whether the authors of included
      studies reported on any possible adverse impact of larvivorous fish introduction
      on non-target native species. MAIN RESULTS: We found no reliable studies that
      reported the effects of introducing larvivorous fish on malaria infection in
      nearby communities, on entomological inoculation rate, or on adult Anopheles
      density.For the secondary analysis, we examined the effects of introducing
      larvivorous fish on the density and presence of anopheline larvae and pupae in
      community water sources. We included 12 small studies, with follow-up from 22
      days to five years. Studies were conducted in a variety of settings, including
      localized water bodies (such as wells, domestic water containers, fishponds, and
      pools; six studies), riverbed pools below dams (two studies), rice field plots
      (three studies), and water canals (two studies). All studies were at high risk of
      bias.The research was insufficient to determine whether larvivorous fish reduce
      the density of Anopheles larvae and pupae (nine studies, unpooled data, very low
      quality evidence). Some studies with high stocking levels of fish seemed to
      arrest the increase in immature anopheline populations, or to reduce the number
      of immature anopheline mosquitoes, compared with controls. However, this finding
      was not consistent, and in studies that showed a decrease in immature anopheline
      populations, the effect was not consistently sustained. Larvivorous fish may
      reduce the number of water sources with Anopheles larvae and pupae (five studies,
      unpooled data, low quality evidence).None of the included studies reported
      effects of larvivorous fish on local native fish populations or other species.
      AUTHORS' CONCLUSIONS: Reliable research is insufficient to show whether
      introducing larvivorous fish reduces malaria transmission or the density of adult
      anopheline mosquito populations.In research examining the effects on immature
      anopheline stages of introducing fish to potential malaria vector breeding sites
      (localized water bodies such as wells and domestic water sources, rice field
      plots, and water canals) weak evidence suggests an effect on the density or
      presence of immature anopheline mosquitoes with high stocking levels of fish, but
      this finding is by no means consistent. We do not know whether this translates
      into health benefits, either with fish alone or with fish combined with other
      vector control measures. Our interpretation of the current evidence is that
      countries should not invest in fish stocking as a larval control measure in any
      malaria transmission areas outside the context of carefully controlled field
      studies or quasi-experimental designs. Research could also usefully examine the
      effects on native fish and other non-target species.

PMID- 24323309
TI  - Occult nodal disease in patients with failed laryngeal preservation undergoing
      surgical salvage.
AB  - OBJECTIVES/HYPOTHESIS: The primary objective was to determine the incidence of
      pathologically positive lymph nodes in clinically N0 larynx cancer patients
      undergoing salvage surgery following nonsurgical primary therapy. Secondary aims
      included assessment of the impact of laryngeal subsite and neck dissection on
      disease status and survival. STUDY DESIGN: Retrospective chart review. METHODS:
      Sixty-eight patients with recurrent laryngeal cancer and no evidence of neck
      disease who underwent salvage laryngectomy and neck dissection after undergoing
      failed primary radiotherapy or chemoradiation were examined. Main outcome
      measures included: standard demographics, primary, clinical, radiologic, and
      pathologic recurrent TNM stage, laryngeal subsite, nodal neck level, surgical
      intervention, margin status, disease status, survival, and imaging results.
      RESULTS: Fifty-three men and 15 women, aged 33 to 88 years (mean=62.7 years) with
      recurrent laryngeal cancer were included. Overall, 28.3% of patients had
      pathologic nodal disease, with supraglottic cancer showing the highest rate (60%,
      P=.02). Survival was not associated with laryngectomy type (P=.35). However, on
      multivariate analysis, laryngeal subsite was significantly predictive of survival
      with transglottic recurrences demonstrating decreased mean survival (20.7 months,
      P=.02), and supraglottic recurrences demonstrating prolonged mean survival (37.1
      months, P=.03). Metabolic imaging (negative predictive value=0.86) proved more
      reliable than anatomic imaging (negative predictive value=0.71). CONCLUSIONS: The
      incidence of pathologically positive lymph nodes in clinically negative patients
      with recurrent laryngeal carcinoma following nonsurgical therapy warrants
      standard selective neck dissection. Subsite of recurrence, specifically
      supraglottis and transglottis, correlates with pathologic neck node positivity
      and survival. Metabolic imaging proved more reliable than anatomic imaging in
      negative predictability for nodal disease. LEVEL OF EVIDENCE: 4.

PMID- 24323310
TI  - The effectiveness of low-dose versus high-dose 99mTc MIBI protocols for
      radioguided surgery in patients with primary hyperparathyroidism.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy of low-dose and high
      dose (99m)Tc methoxy isobutyl isonitrile (MIBI) protocols in intraoperative
      localization of parathyroid adenomas by means of a gamma probe in patients with
      primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: The study included 62
      patients with PHPT who were divided into two groups. Group 1 consisted of 32
      patients who were injected with a low dose (1 mCi) of (99m)Tc MIBI in the
      surgical suite 10 min before incision. Group 2 included 30 patients who were
      intravenously administered a high dose (15 mCi) of (99m)Tc MIBI 2 h before
      surgery. With the aid of a gamma probe, intraoperative localization of
      parathyroid adenomas was performed in both groups of patients who underwent
      minimally invasive parathyroidectomy. All lesions thought to be parathyroid
      adenomas were excised and subsequently evaluated histopathologically. RESULTS:
      All parathyroid adenomas in both groups were localized and excised by means of an
      intraoperative gamma probe. The sensitivity, specificity, and accuracy of low
      dose and high-dose (99m)Tc MIBI protocols in the intraoperative localization of
      adenomas in patients with PHPT were 100%. CONCLUSION: In the light of these
      findings, we conclude that low-dose (99m)Tc MIBI may be preferred to
      intraoperative identification of parathyroid adenomas by means of a gamma probe
      in PHPT patients because it appears to be as effective as high-dose (99m)Tc MIBI.
      Moreover, the low-dose protocol does not have the disadvantages of high-dose
      protocol.

PMID- 24323311
TI  - The value of semiquantitative analysis in identifying diffuse bone marrow
      involvement in follicular lymphoma.
AB  - AIM: The aim of the study was to investigate the value of fluorine-18
      fluorodeoxyglucose ((18)F-FDG)-PET/computed tomography (CT) in identifying
      diffuse bone marrow (BM) involvement in follicular lymphoma using
      semiquantitative assessment. METHODS: This is a retrospective analysis of 41
      patients with grade 1-3a follicular lymphoma who underwent (18)F-FDG-PET/CT,
      contrast-enhanced CT and bone marrow trephine biopsy (BMB) as part of staging. BM
      involvement on PET/CT was assessed by visual and semiquantitative analysis.
      Standardized uptake values (SUVmax) were measured at the sternum, at both iliac
      blades and at the T12 vertebra. An average of these four measurements was
      recorded as SUVav. The single highest overall SUVmax for the four bone sites, the
      SUVav and the ratios SUVav/mediastinal blood pool (MBP) and SUVav/liver were
      compared with the BMB result. RESULTS: Focal bone uptake was identified on (18)F
      FDG-PET/CT by visual analysis in six patients, including two cases in which the
      BMB was negative. Assessment of diffuse BM involvement on (18)F-FDG-PET/CT by
      visual analysis had a sensitivity and specificity of 31 and 92%, respectively.
      Semiquantitative analysis resulted in an improved sensitivity and specificity of
      58 and 96%, respectively, when using SUVav greater than or equal to 2 as the
      cutoff. Using the ratio SUVav/MBP greater than or equal to 1 the sensitivity of
      (18)F-FDG-PET/CT to detect BM involvement improved to 83%. CONCLUSION: Visual
      analysis is useful in determining focal bone involvement, whereas
      semiquantitative analysis using SUVav/MBP has a high sensitivity and specificity
      for predicting BM involvement in patients lacking focal bone lesions.

PMID- 24323312
TI  - Detection of residual tumor following radiofrequency ablation of liver metastases
      using 18F-FDG PET/PET-CT: a systematic review and meta-analysis.
AB  - Radiofrequency ablation (RFA), an effective, locally directed therapy for
      unresectable liver metastases, can improve the survival of patients. As a
      functional imaging approach, (18)F-fluorodeoxyglucose positron emission
      tomography ((18)F-FDG PET) or PET-computed tomography (PET-CT) may play a crucial
      role in the follow-up after RFA. Our objective was to evaluate the diagnostic
      accuracy of (18)F-FDG PET or PET-CT for the detection of residual tumor following
      RFA of liver metastases. Studies reporting the diagnostic value of (18)F-FDG PET
      or PET-CT for patients with residual tumor after RFA of liver metastases were
      identified. The methodological quality of these studies was systematically
      evaluated, and the overall sensitivity and specificity of these data sets are
      reported. Seven studies involving 155 patients were examined. When (18)F-FDG PET
      or PET-CT was performed within 2 days of RFA, the overall sensitivity and
      specificity were 79% [95% confidence interval (CI): 70-87%] and 84% (95% CI: 75
      91%), respectively. When (18)F-FDG PET or PET-CT was performed 1 week after
      treatment, the pooled sensitivity and specificity were 48% (95% CI: 18-79%) and
      94% (95% CI: 70-100%), respectively. Finally, when (18)F-FDG PET or PET-CT was
      performed 3 months after treatment, the pooled sensitivity and specificity were
      52% (95% CI: 22-81%) and 94% (95% CI: 70-100%), respectively. Both (18)F-FDG PET
      and PET-CT are effective in detecting residual tumor following RFA of liver
      metastases. The ideal time to perform these imaging studies is within 2 days of
      RFA treatment.

PMID- 24323314
TI  - Thrombomodulin's lectin-like domain reduces myocardial damage by interfering with
      HMGB1-mediated TLR2 signalling.
AB  - AIMS: Thrombomodulin (TM), via its lectin-like domain (LLD), exhibits anti
      inflammatory properties partly by sequestering the pro-inflammatory cytokine,
      high-mobility group box 1 (HMGB1). Since myocardial damage after ischaemia and
      reperfusion is mediated by inflammation, we evaluated the cardioprotective
      effects of the LLD of TM. Using an in vivo mouse model of transient ischaemia and
      in vitro models of cardiomyocyte hypoxia, we assessed the ability of the LLD to
      suppress HMGB1-mediated activation of the receptors, receptor for advanced
      glycation endproducts (RAGEs) and Toll-like receptors (TLRs) 2 and 4. METHODS AND
      RESULTS: Thirty-minute myocardial ischaemia was induced in isoflurane
      anaesthetized mice followed by 24 h of reperfusion in wild-type (WT) mice, in
      mice lacking the LLD of TM (TM(LeD/LeD) mice), and in WT with systemic
      overexpression of the LLD of TM induced by hydrodynamic transfection. Infarct
      size, HMGB1 protein, and apoptotic cells were significantly increased in
      TM(LeD/LeD) mice when compared with WT. Neonatal rat cardiomyocytes transfected
      with TLR2-, TLR4-, and RAGE-siRNA were exposed to hypoxia (0.8% O2) and
      reoxygenation (21% O2). HMGB1 augmented hypoxia-induced apoptosis in TLR2- but
      not in RAGE- or TLR4-suppressed cells. Administration of HMGB1- and TLR2-blocking
      antibodies in TM(LeD/LeD) mice prior to myocardial ischaemia diminished
      apoptosis. Therapeutic systemic gene therapy using the LLD reduced the infarct
      size and HMGB1 protein levels 24 h after reperfusion. CONCLUSION: The LLD of TM
      suppresses HMGB1-induced and TLR2-mediated myocardial reperfusion injury and
      apoptosis in vitro and in vivo.

PMID- 24323313
TI  - Peptide receptor radionuclide therapy for aggressive atypical pituitary
      adenoma/carcinoma: variable clinical response in preliminary evaluation.
AB  - PURPOSE: There are limited treatment options for progressive atypical pituitary
      adenomas and carcinomas. Peptide receptor radionuclide therapy that targets
      somatostatin receptors has recently been proposed as a potential treatment
      option. The theoretical rationale for efficacy is elegant but evaluation of
      outcomes in the first patients treated for this indication is required to assess
      whether further study is warranted. METHODS: We performed a case review of the
      three pituitary patients we have treated with (177)Lutetium DOTATATE in our
      institution (two atypical adenomas, one carcinoma) and dosimetric analysis of the
      radiation uptake in one patient. RESULTS: Treatment was well tolerated. One
      patient with slowly progressive pituitary carcinoma has stable disease 40 months
      after completing the planned 4 cycles of treatment. Two patients with rapidly
      progressive atypical adenomas terminated treatment early due to continued disease
      progression. Dosimetric evaluation revealed inhomogenous uptake across the tumour
      (1.3-11.9 Gy with one cycle). CONCLUSION: We have found mixed results in our
      first 3 patients with stable disease achieved only in the patient with the more
      slowly progressive tumour. As only a limited number of centres offer Peptide
      receptor radionuclide therapy, a formal study with prospective data collection
      may be feasible and if carried out should include dosimetric evaluation of
      absorbed dose.

PMID- 24323315
TI  - DJ-1/park7 modulates vasorelaxation and blood pressure via epigenetic
      modification of endothelial nitric oxide synthase.
AB  - AIMS: DJ-1/park7, a multifunctional protein, may play essential roles in the
      vascular system. However, the function of DJ-1/park7 in vascular contractility
      has remained unclear. The present study was designed to investigate whether the
      DJ-1/park7 is involved in the regulation of vascular contractility and systolic
      blood pressure (SBP). METHODS AND RESULTS: Norepinephrine (NE) elevated
      contraction in endothelium-intact vessels in a dose-dependent manner, to a
      greater extent in DJ-1/park7 knockout (DJ-1/park7(-/-)) mice than in wild-type
      (DJ-1/park7(+/+)) mice. Acetylcholine inhibited NE-evoked contraction in
      endothelium-intact vessels, and this was markedly impaired in DJ-1/park7(-/-)
      mice compared with DJ-1/park7(+/+). Nitric oxide (NO) production (82.1 +/- 2.8%
      of control) and endothelial NO synthase (eNOS) expression (61.7 +/- 8.9%) were
      lower, but H2O2 production (126.4 +/- 8.6%) was higher, in endothelial cells from
      DJ-1/park7(-/-) mice than in those from DJ-1/park7(+/+) controls; these effects
      were reversed by DJ-1/park7-overexpressing endothelial cells from DJ-1/park7(-/-)
      mice. Histone deacetylase (HDAC)-1 recruitment and H3 histone acetylation at the
      eNOS promoter were elevated and diminished, respectively, in DJ-1/park7(-/-) mice
      compared with DJ-1/park7(+/+) controls. Moreover, SBP was significantly elevated
      in DJ-1/park7(-/-) mice compared with DJ-1/park7(+/+) controls, but this
      elevation was inhibited in mice treated with valproic acid, an inhibitor of Class
      I HDACs including HDAC-1. CONCLUSION: These results demonstrate that DJ-1/park7
      protein may be implicated in the regulation of vascular contractility and blood
      pressure, probably by the impairment of NO production through H2O2-mediated
      epigenetic inhibition of eNOS expression.

PMID- 24323316
TI  - The CCR5 chemokine receptor mediates vasoconstriction and stimulates intimal
      hyperplasia in human vessels in vitro.
AB  - AIMS: The chemokine receptor CCR5 and its inflammatory ligands have been linked
      to atherosclerosis, an accelerated form of which occurs in saphenous vein graft
      disease. We investigated the function of vascular smooth muscle CCR5 in human
      coronary artery and saphenous vein, vascular tissues susceptible to
      atherosclerosis, and vasospasm. METHODS AND RESULTS: CCR5 ligands were
      vasoconstrictors in saphenous vein and coronary artery. In vein, constrictor
      responses to CCL4 were completely blocked by CCR5 antagonists, including
      maraviroc. CCR5 antagonists prevented the development of a neointima after 14
      days in cultured saphenous vein. CCR5 and its ligands were expressed in normal
      and diseased coronary artery and saphenous vein and localized to medial and
      intimal smooth muscle, endothelial, and inflammatory cells. [(125)I]-CCL4 bound
      to venous smooth muscle with KD = 1.15 +/- 0.26 nmol/L and density of 22 +/- 9
      fmol mg(-1) protein. CONCLUSIONS: Our data support a potential role for CCR5 in
      vasoconstriction and neointimal formation in vitro and imply that CCR5 chemokines
      may contribute to vascular remodelling and augmented vascular tone in human
      coronary artery and vein graft disease. The repurposing of maraviroc for the
      treatment of cardiovascular disease warrants further investigation.

PMID- 24323317
TI  - Blocking the EP3 receptor for PGE2 with DG-041 decreases thrombosis without
      impairing haemostatic competence.
AB  - AIMS: Haemostasis interrupts bleeding from disrupted blood vessels by activating
      platelet aggregation and coagulation. A similar mechanism termed thrombosis
      generates obstructive thrombi inside diseased arteries. As a consequence of this
      similarity, current anti-thrombotic agents increase the risk of bleeding.
      Atherosclerotic plaques produce significant amounts of prostaglandin E2 (PGE2),
      which activates its receptor EP3 on platelets and aggravates atherothrombosis. We
      investigated whether blocking EP3 could dissociate atherothrombosis from
      haemostasis. METHODS AND RESULTS: Inhibiting in vivo the receptor EP3 for PGE2
      with the blocking agent DG-041 reduced murine thrombosis triggered by local
      delivery of arachidonic acid or ferric chloride on healthy arteries. Importantly,
      it also reduced thrombosis triggered by scratching murine atherosclerotic
      plaques. PGE2 was not produced at the bleeding site after tail clipping.
      Consistently, blocking EP3 did not alter murine tail, liver, or cerebral
      haemostasis. Furthermore, blocking EP3 reduced murine pulmonary embolism and
      intensified platelet inhibition by clopidogrel leaving tail bleeding times
      unchanged. Human atherosclerotic plaques produced PGE2, which facilitated
      platelet aggregation in human blood and rescued the function of P2Y12-blocked
      platelets. Finally, in healthy patients, DG-041 reduced platelet aggregation, but
      did not significantly alter the cutaneous bleeding time at doses up to eight
      times the dose that inhibited the facilitating effect of PGE2 on platelets.
      CONCLUSION: In mice, blocking EP3 inhibited atherothrombosis without affecting
      haemostasis and intensified efficiency of conventional anti-platelet treatment
      without aggravating the bleeding risk. In patients, blocking EP3 should improve
      the prevention of cardiovascular diseases, which is currently limited by the risk
      of bleeding.

PMID- 24323319
TI  - Assessing the regional impacts of increased energy maize cultivation on farmland
      birds.
AB  - The increasing cultivation of energy crops in Germany substantially affects the
      habitat function of agricultural landscapes. Precise ex ante evaluations
      regarding the impacts of this cultivation on farmland bird populations are rare.
      The objective of this paper was to implement a methodology to assess the regional
      impacts of increasing energy maize cultivation on the habitat quality of
      agricultural lands for farmland birds. We selected five farmland bird indicator
      species with varying habitat demands. Using a crop suitability modelling
      approach, we analysed the availability of potential habitat areas according to
      different land use scenarios for a real landscape in Northeast Germany. The model
      was based on crop architecture, cultivation period, and landscape preconditions.
      Our results showed that the habitat suitability of different crops varied between
      bird species, and scenario calculations revealed an increase and a decrease in
      the size of the potential breeding and feeding habitats, respectively. The
      effects observed in scenario 1 (increased energy maize by 15%) were not
      reproduced in all cases in scenario 2 (increased energy maize by 30%). Spatial
      aggregation of energy maize resulted in a negative effect for some species.
      Changes in the composition of the farmland bird communities, the negative effects
      on farmland bird species limited in distribution and spread and the relevance of
      the type of agricultural land use being replaced by energy crops are also
      discussed. In conclusion, we suggest a trade-off between biodiversity and energy
      targets by identifying biodiversity-friendly energy cropping systems.

PMID- 24323318
TI  - A critical evaluation of behavioral rodent models of motor impairment used for
      screening of antiparkinsonian activity: The case of adenosine A(2A) receptor
      antagonists.
AB  - Animal models of motor dysfunction constitute the basis for the screening of new
      drugs with potential efficacy in diseases characterized by motor impairment, such
      as Parkinson's Disease (PD). Taking adenosine A(2A) receptor antagonists as an
      example of a new class of drugs for PD, the review will examine the most utilized
      rodent models of motor impairment and the results reported in the literature with
      this class of drugs. The results obtained so far in rodent models of PD suggested
      that A(2A) receptor antagonists might have symptomatic therapeutic efficacy in
      PD. They may ameliorate initiation of movement, gait and muscle rigidity,
      sensorimotor integration deficits, and tremor. Moreover, A(2A) receptor
      antagonists when administered with a low sub-threshold dose of L-DOPA potentiated
      its efficacy. However, the clinical trials so far performed have evaluated their
      efficacy in the "ON/OFF" of PD patients with motor complications, showing a
      limited efficacy of this class of drug. Therefore, on one hand, animal models of
      PD might have a limited validity; on the other hand, clinical trials should
      explore the efficacy of A(2A) receptor antagonists on a broader range of
      parkinsonian conditions.

PMID- 24323320
TI  - Assessment of some remote sensing techniques used to detect land use/land cover
      changes in South-East Transilvania, Romania.
AB  - This paper assesses the image differencing technique for the Normalized
      Difference Vegetation Index (NDVI), the second principal component (PC2), and the
      TM 4 band (TM 4), as well as the post-classification comparison (PCC) in order to
      analyze the land use/land cover changes in the South-East Transilvania, Romania.
      The analysis was performed using two frames from Landsat 5 TM satellite images
      acquired on August 5, 1993 and July 24, 2009. After applying the NDVI, PC2, and
      TM 4 image differencing techniques, the images obtained were transformed into
      change/no change maps. The thresholds identified to highlight the changes were
      set at 0.6 s for NDVI and 0.7 s for PC2 and TM 4. Before applying the PCC
      technique, the satellite images were classified through the supervised
      classification method. The overall accuracy obtained was 85.91 % and the kappa
      statistics 0.8249 for 1993, 88.18 % and 0.8497 for 2009, respectively. The
      assessment of the changes detection methods in the studied area shows that the
      first place is occupied by NDVI image differencing with an overall accuracy of
      83.80 %, followed by PCC method with 83.20 %, PC2 difference with an overall
      accuracy of 81.60 %, and TM 4 difference with an overall accuracy of 79.40 %.

PMID- 24323321
TI  - Histopathological and ultrastructural perturbations in tilapia liver as potential
      indicators of pollution in Lake Al-Asfar, Saudi Arabia.
AB  - Lake Al-Asfar (Al-Hassa, Saudi Arabia) is under threat from contaminants released
      through human activities such as agriculture and urban and industrial
      developments. In the present study, histopathologic and ultrastructural changes
      in liver of tilapia Oreochromis niloticus were analyzed to monitor the possible
      impact of pollution in Al-Asfar estuary. Heavy metals such as Ni, Fe, Zn, Co, Ba,
      Pb, and Cd were predominant in the lake water and far exceeded the international
      permissible limits. In fish samples, high prevalences of preneoplastic changes
      (50 %) and one case of cholangiocarcinoma were revealed in liver tissues.
      Cytological damage in fish hepatocytes included glycogen exhaustion, deformation
      of nuclear envelope, heterochromatin condensation, mitochondrial degeneration,
      vesiculation of rough endoplasmic reticulum, augmentation of smooth endoplasmic
      reticulum, and lysosomal proliferation. In conclusion, the observed biomarker
      responses were potential indicators of health impairment or disease in field fish
      populations, although there was no direct proof of a simple cause-effect
      relationship. This is the first biological effect assessment in Lake Al-Asfar
      using tilapia as suitable target species.

PMID- 24323322
TI  - Aqueous stabilization of carbon nanotubes: effects of surface oxidization and
      solution chemistry.
AB  - Surface oxygen functional groups can affect the morphological characteristics,
      aggregation kinetics, and adsorption capacity of multi-walled carbon nanotubes
      (MWCNTs). However, little is known about the quantitative relationship between
      oxygen content and the dispersion stability of MWCNTs. To investigate the effects
      of surface oxidization, MWCNTs were oxidized using concentrated H2SO4/HNO3 acids
      for 0, 1, 2, 4, and 8 h, respectively. Experimental results showed that the
      oxygen content of MWCNTs increased with surface oxidization time. Linear
      correlations were found to exist between the oxygen content, critical coagulation
      concentration (CCC) for NaCl, and critical coagulation pH values of MWCNTs
      detected by optical density at 800 nm. The CCC values for CaCl2 increased with
      oxygen contents for unmodified MWCNTs and lowly oxidized MWCNTs, while which
      decreased after further increasing the surface oxidization. CCC ratios in the
      presence of Ca(2+) to Na(+) were consistent with the empirical Schulze-Hardy rule
      for unmodified MWCNTs and lowly oxidized MWCNTs; however, which were much lower
      than the expected values for highly oxidized MWCNTs. Fulvic acid can clearly
      increase the stability of MWCNT suspension with unmodified MWCNTs and lowly
      oxidized MWCNTs, while it cannot affect the dispersion of highly oxidized MWCNTs.
      This study implied that the oxidation and presence of fulvic acid will possibly
      increase the mobility, exposure, bioavailability, and toxicity of MWCNTs.

PMID- 24323323
TI  - Distribution of polybrominated diphenyl ethers and dust particle size fractions
      adherent to skin in indoor dust, Pretoria, South Africa.
AB  - In order to determine human exposure to the indoor toxicant, selection of dust
      fraction and understanding dust particle size distribution in settled indoor dust
      are very important. This study examined the influence of dust particle size on
      the concentration of polybrominated diphenyl ethers (PBDEs) congeners, assessed
      the distribution of dust particle size and characterized the main indoor emission
      sources of PBDEs. Accordingly, the concentrations of PBDE congeners determined in
      different indoor dust fractions were found to be relatively higher in the order
      of dust particle size: 45-106 MUm>(<45 MUm)>106-150 MUm. The finding shows
      arbitrary selection of dust fractions for exposure determination may result in
      wrong conclusions. Statistically significant moderate correlation between the
      concentration of Sigma9PBDEs and organic matter content calculated with respect
      to the total dust mass was also observed (r=0.55, p=0.001). On average, of total
      dust particle size <250 MUm, 93.4 % (m/m%) of dust fractions was associated with
      less than 150 MUm. Furthermore, of skin adherent dust fractions considered (<150
      MUm), 86 % (v/v%) is in the range of particle size 9.25-104.7 MUm. Electronic
      materials treated with PBDEs were found the main emission sources of PBDE
      congeners in indoor environment. Based on concentrations of PBDEs determined and
      mass of indoor dust observed, 150 MUm metallic sieve is adequate for human
      exposure risk assessment. However, research in this area is very limited and more
      research is required to generalize the fact.

PMID- 24323324
TI  - Biotic and abiotic degradation of pesticide Dufulin in soils.
AB  - Dufulin is a newly developed antiviral agent (or pesticide) that activates
      systemic acquired resistance of plants. This pesticide is widely used in China to
      prevent abroad viral diseases in rice, tobacco and vegetables. In this study, the
      potential impacts such as soil type, moisture, temperature, and other factors on
      Dufulin degradation in soil were investigated. Degradation of Dufulin followed
      the first-order kinetics. The half-life values varied from 2.27 to 150.68 days.
      The dissipation of Dufulin was greatly affected by soil types, with DT50
      (Degradation half time) varying between 17.59, 31.36, and 43.32 days for Eutric
      Gleysols, Cumulic Anthrosols, and Dystric Regosols, respectively. The elevated
      moisture accelerated the decay of Dufulin in soil. Degradation of Dufulin
      increased with temperature and its half-life values ranged from 16.66 to 42.79
      days. Sterilization of soils and treatment with H2O2 resulted in a 6- and 8-fold
      decrease in degradation rates compared to the control, suggesting that Dufulin
      degradation was largely governed by microbial processes. Under different light
      spectra, the most effective degradation occurred with 100-W UV light (DT50=2.27
      days), followed by 15-W UV light (DT50=8.32 days) and xenon light (DT50=14.26
      days). Analysis by liquid chromatography-mass spectroscopy (LC-MS) revealed that
      2-amino-4-methylbenzothiazole was one of the major decayed products of Dufulin in
      soils, suggesting that elimination of diethyl phosphate and 2-fluorobenzaldehyde
      was most like the degradation pathway of Dufulin in Eutric Gleysols.

PMID- 24323325
TI  - Micropollutants in urban stormwater: occurrence, concentrations, and atmospheric
      contributions for a wide range of contaminants in three French catchments.
AB  - This study aimed at: (a) providing information on the occurrence and
      concentration ranges in urban stormwater for a wide array of pollutants (n = 77);
      (b) assessing whether despite the differences between various catchments (land
      use, climatic conditions, etc.), the trends in terms of contamination level are
      similar; and (c) analyzing the contribution of total atmospheric fallout (TAF)
      with respect to sources endogenous to this contamination. The studied
      contaminants include conventional stormwater contaminants (polycyclic aromatic
      hydrocarbons (PAHs), Zn, Cu, Pb, etc.), in addition to poorly or undocumented
      pollutants such as nonylphenol and octylphenol ethoxylates (NPnEO and OPnEO),
      bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), a wide variety of
      pesticides, and various metals of relevance (As, Ti, Sr, V). Sampling and
      analysis were performed using homogeneous methods on three urban catchments with
      different land use patterns located in three distinct French towns. For many of
      these pollutants, the results do not allow highlighting a significant difference
      in stormwater quality at the scale of the three urban catchments considered.
      Significant differences were, however, observed for several metals (As, Cr, Cu,
      Ni, Sr and Zn), PAHs, and PBDEs, though this assessment would need to be
      confirmed by further experiments. The pollutant distributions between dissolved
      and particulate phases were found to be similar across the three experimental
      sites, thus suggesting no site dependence. Lastly, the contributions of TAF to
      stormwater contamination for micropollutants were quite low. This finding held
      true not only for PAHs, as previously demonstrated in the literature, but also
      for a broader range of molecules such as BPA, NPnEO, OPnEO, and PBDEs, whose high
      local production is correlated with the leaching of urban surfaces, buildings,
      and vehicles. 

PMID- 24323326
TI  - Metals bioaccumulation and histopathological biomarkers in Carcinus maenas crab
      from Bizerta lagoon, Tunisia.
AB  - Metals concentrations and histolopathological lesions of gills and digestive
      gland were investigated in Carcinus maenas crabs sampled from Bizerta Lagoon and
      Kuriat Island (Tunisia) as control site. The concentrations of trace metals
      varied between tissues, sites and sampling time. The highest levels of the
      analysed metals in gills and digestive gland were noted in Menzel Bourguiba and
      Cimentery sites at both sampling times (February and July). The higher metals
      loads were associated with severe and various tissues alterations in contaminated
      crabs. We particularly noted in the gills a haemocytic infiltration, distension
      and enlargement of the lamellae, lifting of lamellar epithelium, necrotic lesions
      and fusion of lamellae in the most polluted sites (Menzel Bourguiba and
      Cimentery). Moreover, others pathological alterations were observed in digestive
      gland of crabs collected from polluted sites and with a severity site dependent.
      We observed necrotic tubules containing tissue debris in the lumen with more
      intensity in crabs collected from Cimentery site in both sampling times. The
      thickened basal laminae and the walling off of the tubules by haemocytes around
      the thickened basal laminae were more abundant at Menzel Bourguiba than at others
      sites. The coagulation in the thickened basal laminae was observed only at
      Cimentery in February. Tissues histopathological lesions were sensitive to
      discriminate crabs of different sites and demonstrated its usefulness in this
      biomonitoring study. We recommend the association of histopatholocial lesions to
      biochemical biomarkers in future biomonitoring studies.

PMID- 24323327
TI  - The role of humic acid in the toxicity of arsenite to the diatom Navicula sp.
AB  - Dissolved organic matter (DOM) affects arsenite [As(III)] toxicity by altering
      its sorption equilibrium at the cell wall interface. A better understanding of
      such mechanism is of great importance to assess As(III) ecotoxicity in aquatic
      systems. Batch experiments were conducted to study the effects of DOM on the
      regulation of As(III) sorption and toxicity in the diatom Navicula sp. The
      influence of humic acid (HA) on As(III) toxicity was assessed by measuring algal
      growth, chlorophyll a, and reactive oxygen species (ROS), whereas As(III)
      mobility across the cell wall was estimated by determining the concentration of
      intracellular, cell-wall-bound, and free As(III) ions in cell media. Results
      showed that the effects of HA on arsenite toxicity varied depending on various
      combinations of As(III)-HA concentrations. EC50 had an approximate threefold
      increase from 8.32 (HA-free control) to 22.39 MUM (at 20 mg L(-1) HA) when
      Navicula sp. was exposed to 1.0-100.0 MUM of As(III), compared to an overall low
      complexation ratio of HA-As(III) in a range of 0.91-6.00 %. The cell wall-bound
      and intracellular arsenic content decreased by 19.8 and 20.3 %, respectively,
      despite the lower arsenite complexation (2.10 +/- 0.16 % of the total As).
      Meanwhile, intracellular ROS was decreased by 12.6 % in response to 10.0 MUM
      As(III) and 10 mg L(-1) HA vs. the HA-free control. The significant contrast
      indicated that complexation alone could not explain the HA-induced reduction in
      arsenite toxicity and other factors including HA-cell surface interactions may
      come into play. Isotherms describing adsorption of HA to the Navicula sp. cells
      combined with morphological data by scanning electron microscopy revealed a
      protective HA floccule coating on the cell walls. Additional Fourier transform
      infrared spectroscopic data suggested the involvement of carboxylic groups during
      the adsorption of both HA and As(III) on the Navicula sp. cell surface.
      Collective data from this study suggest that cell wall-bound HA can moderate
      As(III) toxicity through the formation of a protective floccule coating occupying
      As(III) sorption sites and decreased effective functional groups capable of
      binding As(III). Our findings imply that As(III) toxicity can be alleviated due
      to the increased hindrance to cellular internalization of As(III) in the presence
      of naturally abundant DOM in water.

PMID- 24323328
TI  - Reply: To PMID 23239522.

PMID- 24323329
TI  - Robotic-assisted simple prostatectomy: a systematic review and report of a single
      institution case series.
AB  - Open simple prostatectomy (OSP) is an effective treatment for patients with
      symptomatic BPH and larger volume prostates; however, it is associated with
      substantial risks of bleeding, transfusion and prolonged hospital length of stay
      (LOS). Robotic-assisted simple prostatectomy (RASP) potentially offers improved
      perioperative outcomes for these patients. We systematically reviewed published
      data on RASP outcomes and analyzed our experience at the University of California
      San Diego (UCSD). We identified eight published studies, all non-comparative case
      series (Level 3 evidence), reporting a total of 109 RASP cases from 2008 to 2012.
      Indications included acute urinary retention (n=48), persistent obstructive
      symptoms (n=51), failure of medical management (n=9) and recurrent urinary tract
      infections (n=2). The mean ages ranged from 65 to 77 years. More than 75% of the
      studies reported a mean LOS <3 days and a transfusion prevalence of 0%. The mean
      resected prostate weights ranged from 51 to 301 g. For UCSD, indications for
      surgery included urinary retention (n=11) and failure of medical management
      (n=5). The mean age was 68 years, transfusion prevalence 0%, mean resected
      prostate weight 94 g and mean LOS 1 day. All nine series observed substantial
      postoperative improvements in urinary symptoms and retention. These data suggest
      that RASP is a safe and efficacious treatment for BPH in select patients with
      larger prostates. Although LOS and transfusion prevalence for RASP are markedly
      lower than the published OSP series, comparative studies are needed to verify
      these results. 

PMID- 24323330
TI  - Understanding the side effects of emission trading: implications for waste
      management.
AB  - The trading of emission allowances is an important market instrument in climate
      policy. However, the inclusion of certain branches of industry in the trading
      system not only provides incentives for emission reduction, it also entails
      unwanted side effects. Thus, the objective of the present study is to identify
      such side effects-positive and negative-by examining the potential impact of
      waste management inclusion in the European Union Emissions Trading Scheme (EU
      ETS). Desk research was supplemented with qualitative and quantitative empirical
      analysis (based on expert interviews and a questionnaire) in order to analyse the
      related perceptions and expectations of actors and stakeholders. The impact of
      waste management inclusion in the EU ETS is analysed in terms of the following
      three areas: (i) costs and cost pass-through, (ii), competitiveness and market
      position, and (iii) carbon leakage. Concerning expectations in the area of costs,
      both the interviewed experts and the practitioners surveyed thought that costs
      were likely to increase or that they could be passed on to customers. However,
      experts and practitioners differed with respect to the possibility of carbon
      leakage. Clearly, increased knowledge of the possible impact arising from
      inclusion of the waste sector in the EU ETS would enable managers to become more
      proactive and to manage waste streams and treatment options more economically. 

PMID- 24323331
TI  - Private sector participation in solid waste collection in Addis Ababa (Ethiopia)
      by involving micro-enterprises.
AB  - Privatization of urban services focuses often on the involvement of foreign
      enterprises. This contribution deals with micro-privatization, the partial
      transfer of government responsibility for solid waste collection to micro
      enterprises. It tries to shed light on whether the current private sector
      participation (PSP) of micro-enterprises in solid waste collection service is the
      best way to capture the expected advantages of private sector involvement. The
      article examines the relations of the micro-enterprises with beneficiaries and
      the public sector by focusing on the contract procedure, the tariff-setting
      process, the cost recovery mechanism and institutionalizing of market principles
      for micro-enterprises. The research was carried out using secondary and primary
      data sources. Primary data were collected through the interviewing of public
      sector officials at different levels, focus group discussions with community
      groups and micro-enterprises, and observation. A survey was conducted among 160
      micro-enterprises in the city of Addis Ababa, Ethiopia, using a standard
      questionnaire. What are some of the factors contributing to the results of PSP in
      Addis Ababa, the capital of Ethiopia? Policies at higher levels of government
      definitely produced an overall climate conducive to micro-privatization and
      recognized the need to develop micro-enterprises, but it is not clear what role
      the micro-enterprises are to play in solid waste management. New opportunities
      were created by formalization and taken up by communities and micro-enterprises.
      Coverage and waste collected both increased. The initiation and
      institutionalization of the formalization process was not without problems. The
      public sector over-stressed the autonomy of micro-enterprises. The fate of the
      micro-enterprises is largely determined by the reforms undertaken at local
      government level. The rapid changes in policies at the local level made waste
      collecting micro-enterprises lose confidence and more dependent on the public
      sector. The study shows the continued power of the state and its agents in
      shaping developments in this domain. 

PMID- 24323332
TI  - Liver fat quantification using a multi-step adaptive fitting approach with multi
      echo GRE imaging.
AB  - PURPOSE: The purpose of this study was to develop a multi-step adaptive fitting
      approach for liver proton density fat fraction (PDFF) and R(2)* quantification,
      and to perform an initial validation on a broadly available hardware platform.
      THEORY AND METHODS: The proposed method uses a multi-echo three-dimensional
      gradient echo acquisition, with initial guesses for the fat and water signal
      fractions based on a Dixon decomposition of two selected echoes. Based on
      magnitude signal equations with a multi-peak fat spectral model, a multi-step
      nonlinear fitting procedure is then performed to adaptively update the fat and
      water signal fractions and R(2)* values. The proposed method was validated using
      numeric phantoms as ground truth, followed by preliminary clinical validation of
      PDFF calculations against spectroscopy in 30 patients. RESULTS: The results of
      the proposed method agreed well with the ground truth of numerical phantoms, and
      were relatively insensitive to changes in field strength, field homogeneity,
      monopolar/bipolar readout, signal to noise ratio, and echo time selections. The
      in vivo patient study showed excellent consistency between the PDFF values
      measured with the proposed approach compared with spectroscopy. CONCLUSION: This
      multi-step adaptive fitting approach performed well in both simulated and initial
      clinical evaluation, and shows potential in the quantification of hepatic
      steatosis.

PMID- 24323333
TI  - Non-natural G-quadruplex in a non-natural environment.
AB  - The biocompatibility as well as the sustainability of a deep eutectic solvent
      makes it a good substitute for aqueous media in studying biomolecules.
      Understanding the structure and stability of natural and non-natural G
      quadruplexes in aqueous and highly viscous media will be useful in biological and
      nanodevice applications. We report the synthesis and conformational analysis of a
      model G-rich oligonucleotide G3T3 and non-natural G-rich sequences Pyr1-Pyr3 in
      aqueous and highly viscous media. Progressive increases in the loop replacement
      with a non-natural pyrene linker leads to a systematic increase of the thermal
      denaturation temperature of the modified G-rich oligonucleotides Pyr1-Pyr3 in 10
      mM cacodylate buffer (pH 7.2) containing 100 mM KCl, as monitored using UV-Vis
      spectroscopy. A circular dichroism signal clearly revealed the formation of a
      predominantly anti-parallel vs. parallel conformation in the natural G-rich
      oligonucleotide G3T3 as well as the non-natural G-rich oligonucleotides Pyr1-Pyr3
      in 10 mM cacodylate buffer (pH 7.2) containing 100 mM KCl. On the other hand, we
      observed thermodynamic destabilization of G-rich oligonucleotides in a deep
      eutectic solvent (DES; 1 : 2 choline chloride-urea) containing 100 mm KCl with an
      increase in loop replacements. Interestingly, we observed an exclusively parallel
      G-quadruplex conformation in the case of G3T3 in DES containing 100 mm KCl. While
      pyrene containing G-rich oligonucleotides Pyr1-Pyr3 exhibited a predominantly
      parallel vs. anti-parallel G-quadruplex conformation in DES containing 100 mM
      KCl.

PMID- 24323334
TI  - Preterm birth and maternal psychological health.
AB  - Studies have shown that preterm birth significantly influences mothers'
      psychological health. This study aimed to identify factors associated with
      preterm birth and assess postnatal depression and anxiety symptoms in mothers of
      preterm infants (n = 75) compared to mothers who delivered at term (n = 125) in a
      Greek sample. Multiple pregnancies, assisted reproduction technology, caesarean
      section, non-Greek ethnicity and smoking during pregnancy were associated with
      preterm delivery. Moreover, preterm infants' mothers had higher depression, state
      anxiety and trait anxiety scores. These findings suggest that addressing
      preventable causes of preterm delivery is crucial, while mothers of preterm
      infants should receive postnatal support. 

PMID- 24323335
TI  - A biopsychosocial model of resilience for multiple sclerosis.
AB  - The concept of resilience remains under-researched in the multiple sclerosis
      literature. Consequently, current understanding of the unique and joint
      contribution of disability-specific variables, cognitive-behavioural skills and
      social resources to this dynamic process is limited. A holistic model of
      resilience was therefore developed and tested. Results of an online survey
      completed by 196 adults with multiple sclerosis revealed both direct and indirect
      pathways to resilience, with positive affect and self-efficacy being the
      strongest predictors. The findings lend support to psychological interventions
      which focus on promoting the personal resources and assets needed to cope
      effectively with multiple sclerosis. 

PMID- 24323336
TI  - Special issue of translational stroke: importance of sex in the pathophysiology
      and treatment of acute CNS repair.

PMID- 24323339
TI  - The management of sport-related concussion: considerations for male and female
      athletes.
AB  - Sport-related concussion continues to be a centerpiece of attention in the field
      of sports medicine. The benefit to using neurocognitive testing when managing
      concussion will be documented in this review. In addition to providing critical
      objective information on the neurocognitive status of the concussed athlete,
      research data will be provided on the pre- and post-concussion neurocognitive
      profiles of concussed male and female athletes. Specifically, an overview of
      research will be presented on the epidemiology of male and female concussion
      rates, as well as concussion outcomes including symptoms and cognitive function
      post-injury. Finally, a clinician's perspective on managing sports-related
      concussion will be presented focusing on three factors regarding sex differences:
      risk factors, clinical presentation, and management. 

PMID- 24323337
TI  - The effects of estrogen in ischemic stroke.
AB  - Stroke is a leading cause of death and the most common cause of long-term
      disability in the USA. Women have a lower incidence of stroke compared with men
      throughout most of the lifespan which has been ascribed to protective effects of
      gonadal steroids, most notably estrogen. Due to the lower stroke incidence
      observed in pre-menopausal women and robust preclinical evidence of
      neuroprotective and anti-inflammatory properties of estrogen, researchers have
      focused on the potential benefits of hormones to reduce ischemic brain injury.
      However, as women age, they are disproportionately affected by stroke, coincident
      with the loss of estrogen with menopause. The risk of stroke in elderly women
      exceeds that of men and it is clear that in some settings estrogen can have pro
      inflammatory effects. This review will focus on estrogen and inflammation and its
      interaction with aging. 

PMID- 24323338
TI  - Oral contraceptives and nicotine synergistically exacerbate cerebral ischemic
      injury in the female brain.
AB  - Oral contraceptives (OC) and smoking-derived nicotine (N) are known to
      synergistically increase the risk and severity of cerebral ischemia in women.
      Although it has been known for some time that long-term use of OC and nicotine
      will have an increased risk of peripheral thrombus formation, little is known
      about how the combination of OC and nicotine increases severity of brain
      ischemia. Recent laboratory studies simulating the conditions of nicotine
      exposure produced by cigarette smoking and OC regimen of women in female rats
      confirms that the severity of ischemic hippocampal damage is far greater in
      female rats simultaneously exposed to OC than to nicotine alone. These studies
      also demonstrated that the concurrent exposure of OC and nicotine reduces
      endogenous 17beta-estradiol levels and inhibits estrogen signaling in the brain
      of female rats. The endogenous 17beta-estradiol plays a key role in
      cerebrovascular protection in women during their pre-menopausal life and loss of
      circulating estrogen at reproductive senescence increases both the incidence and
      severity of cerebrovascular diseases. Therefore, OC and nicotine induced severe
      post-ischemic damage might be a consequence of lack of estrogen signaling in the
      brain. In the present review we highlight possible mechanisms by which OC and
      nicotine inhibits estrogen signaling that could be responsible for severe
      ischemic damage in females. 

PMID- 24323340
TI  - Sport-related concussion: "how many is too many?".
AB  - The long-term effects of multiple sport-related concussions are currently at the
      center of debate in the popular press and scientific community. The question,
      "How many concussions are too many," is frequently asked in the competitive sport
      environment by parents, athletes, and coaches. While research suggests that a
      history of concussion influences the risk and recovery from subsequent
      concussion, studies investigating the long-term effects of multiple concussions
      are less conclusive. This paper reviews the literature on multiple concussions
      and the potential long-term consequences of these injuries. Furthermore, this
      paper addresses how concussion history can inform clinical and return-to-play
      decisions. Recent studies incorporating novel brain imaging and
      electrophysiological technology for assessing residual impairment from multiple
      concussions are reviewed and the clinical implications of this work are
      discussed. 

PMID- 24323341
TI  - Effect of gender on recovery after spinal cord injury.
AB  - Spinal cord injury (SCI) is a debilitating condition that affects thousands of
      new individuals each year, the majority of which are males. Males with SCI tend
      to be injured at an earlier age, mostly during sports or motor vehicle accidents,
      whereas females tend be injured later in life, particularly in the age group 65
      and older. In both experimental and clinical studies, the question as to whether
      gender affects outcome has been addressed in a variety of patient groups and
      animal models. Results from experimental paradigms have suggested that a gender
      bias in outcome exists that favors females and appears to involve the
      advantageous or disadvantageous effects of the gonadal sex hormones estrogen and
      progesterone or testosterone, respectively. However, other studies have shown an
      absence of gender differences in outcome in specific SCI models and work has also
      questioned the involvement of female sex hormones in the observed outcome
      improvements in females. Similar controversy exists clinically, in studies that
      have examined gender disparities in outcome after SCI. The current review
      examines the experimental and clinical evidence for a gender bias in outcome
      following SCI and discusses issues that have made it difficult to conclusively
      answer this question. 

PMID- 24323343
TI  - Meta-analysis of randomized controlled trials on the efficacy of probiotics in
      Helicobacter pylori eradication therapy in children.
AB  - The efficacy of probiotics supplementation in children undergoing Helicobacter
      pylori (H. pylori) eradication therapy remains controversial. This study aimed to
      meta-analyze whether probiotics supplementation in triple therapy could improve
      H. pylori eradication rates and reduce therapy-related side effects in children.
      Electronic databases PubMed and Embase were searched to identify all randomized
      controlled trials in pediatric patients comparing probiotics supplementation with
      placebo or no extra intervention in H. pylori eradication therapy. Two authors
      independently extracted the data. Results were expressed as odds ratios (ORs) and
      accompanying 95 % confidence intervals (CIs). Stata version 12.0 was used to
      perform all statistical analyses. Seven studies consisting of 508 pediatric
      patients were included in our study. The pooled ORs (studies n = 7) of
      eradication rates by intention-to-treat and per-protocol analysis in the
      probiotics group versus the control group were 1.96 (95 % CI 1.28-3.02) and 2.25
      (95 % CI 1.41-3.57), respectively. The pooled OR (studies n = 5) of incidence of
      total side effects was 0.32 (95 % CI 0.13-0.79), with significant heterogeneity
      observed (I (2) = 71.9 %). CONCLUSION: Probiotics supplementation in triple
      therapy for H. pylori infection may have beneficial effects on eradication and
      therapy-related side effects, particularly diarrhea, in children.

PMID- 24323344
TI  - Five-year experience of clinical ethics consultations in a pediatric teaching
      hospital.
AB  - Our retrospective study presents and evaluates clinical ethics consultations
      (CECs) in pediatrics as a structure for implementing hospital-wide ethics. We
      performed a descriptive and statistical analysis of clinical ethics decision
      making and its implementation in pediatric CECs at Zurich University Children's
      Hospital. Ninety-five CECs were held over 5 years for 80 patients. The care team
      reached a consensus treatment recommendation after one session in 75
      consultations (89 %) and on 82 of 84 ethical issues (98 %) after two or more
      sessions (11 repeats). Fifty-seven CECs recommended limited treatment and 23
      maximal treatment. Team recommendations were agreed outright by parents and/or
      patient in 59 of 73 consultations (81 %). Initial dissensus yielded to
      explanatory discussion or repeat CEC in seven consultations (10 %). In a further
      seven families (10 %), no solution was found within the CEC framework: five (7 %)
      required involvement of the child protection service, and in two families, the
      parents took their child elsewhere. Eventual team-parent/patient consensus was
      reached in 66 of 73 families (90 %) with documented parental/patient decisions
      (missing data, n = 11). Patient preference was assessable in ten CECs. Patient
      autonomy was part of the ethical dilemma in only three CECs. The Zurich clinical
      ethics structure produced a 98 % intra-team consensus rate in 95 CECs and reduced
      initial team-parent dissensus from 21 to 10 %. Success depends closely on a
      standardized CEC protocol and an underlying institutional clinical ethics
      framework embodying a comprehensive set of transparently articulated values and
      opinions, with regular evaluation of decisions and their consequences for care
      teams and families. 

PMID- 24323345
TI  - Hospital paediatricians' workflow interruptions, performance, and care quality: a
      unit-based controlled intervention.
AB  - OBJECTIVE: Frequent workflow interruptions jeopardise clinicians' efficiency and
      quality of clinical care. We sought to determine the effect of a documentation
      assistant intervention. Our hypothesis was that the expected decrease of workflow
      interruptions enhances paediatricians' performance and simultaneously improves
      patients' perceived quality of care. METHODS: This was a controlled intervention
      study with data collected before and after the intervention at a University
      Children's Hospital. For the intervention, a documentation assistant was assigned
      to an inpatient ward. The main outcome measures were workflow interruptions,
      paediatricians' performance, as well as patients' perceived quality of care.
      Workflow interruptions were assessed via standardised expert observations.
      Paediatricians' evaluated their performance in terms of productivity, quality,
      and efficiency. Additionally, standardised patients' reports on perceived quality
      of care were collected. RESULTS: For paediatricians in the intervention ward,
      workflow interruptions decreased significantly from 5.2 to 3.1 disruption events
      per working hour (decrease in the control unit was from 3.8 to 3.1). Furthermore,
      paediatricians reported at follow-up significantly enhanced productivity,
      quality, and efficiency. Similarly, patients' ratings of care quality improved
      significantly over time. In multivariate analyses, we found substantial changes
      attributable to the intervention: for all three outcomes, we found a significant
      interaction effect of the intervention over study time. CONCLUSIONS: The
      intervention streamlined paediatricians' workflow, improved day-to-day
      functioning of the ward, and enhanced organisational efficiency and delivery of
      paediatric care. Future studies should investigate potential influences between
      the reduction of workflow interruptions, paediatricians' perceived performance,
      and patient-related outcomes in quality and efficiency of paediatric care.

PMID- 24323342
TI  - Gender-specific differences in the central nervous system's response to
      anesthesia.
AB  - Males and females are physiologically distinct in their responses to various
      anesthetic agents. The brain and central nervous system (CNS), the main target of
      anesthesia, are sexually dimorphic from birth and continue to differentiate
      throughout life. Accordingly, gender has a substantial impact on the influence of
      various anesthetic agents in the brain and CNS. Given the vast differences in the
      male and female CNS, it is surprising to find that females are often excluded
      from basic and clinical research studies of anesthesia. In animal research, males
      are typically studied to avoid the complication of breeding, pregnancy, and
      hormonal changes in females. In clinical studies, females are also excluded for
      the variations that occur in the reproductive cycle. Being that approximately
      half of the surgical population is female, the exclusion of females in anesthesia
      related research studies leaves a huge knowledge gap in the literature. In this
      review, we examine the reported sex-specific differences in the central nervous
      system's response to anesthesia. Furthermore, we suggest that anesthesia
      researchers perform experiments on both sexes to further evaluate such
      differences. We believe a key goal of research studying the interaction of the
      brain and anesthesia should include the search for knowledge of sex-specific
      mechanisms that will improve anesthetic care and management in both sexes. 

PMID- 24323346
TI  - Improvement rates in adolescent patients with chronic fatigue syndrome after
      receiving cognitive behavioural therapy.

PMID- 24323347
TI  - Improvement rates in adolescent patients with chronic fatigue syndrome after
      receiving cognitive behavioural therapy. Correspondence in response to: Clinical
      Practice: chronic fatigue syndrome-author's reply.

PMID- 24323348
TI  - Total knee arthroplasty in elderly patients with severe Kashin-Beck disease of
      the knee.
AB  - PURPOSE: The treatment of elderly KBD knee remains a significant clinical
      challenge, and clinical data are lacking. This study aimed to prospectively
      determine the functional outcomes of total knee arthroplasty (TKA) in adult
      patients with severe Kashin-Beck disease (KBD) of the knee. METHOD: Fifteen cases
      that included 18 occurrences of KBD of the knee were treated by primary knee
      arthroplasty and followed up for at least two years. Clinical assessments for
      each patient were performed at time zero (pre-operatively), one, three, six and
      12 months and yearly thereafter. The efficacy measures included the visual
      analogue scale (VAS) pain score, Hospital for Special Surgery (HSS) score, and
      Functional Score for Adult Tibetans with Kashin-Beck Disease (FSAT-KBD) as well
      as radiographic findings. RESULTS: All patients were followed for a mean length
      of 32.47+/-10.05 months. All force lines in the lower limbs had been improved
      significantly. No radiographic evidence of loosening or changes in component
      positioning was observed at the last follow up. The VAS decreased significantly
      during the first six months after surgery and was maintained until the last
      follow up (p < 0.01). Similar trends were found in both HSS and FSAT-KBD, which
      increased significantly post-operatively (p < 0.01). CONCLUSION: Knee
      arthroplasty can reduce pain and improve function in patients with severe KBD of
      the knee. Additional studies will be necessary to confirm our findings.

PMID- 24323349
TI  - Outcomes after shoulder arthroplasty revision with glenoid reconstruction and
      bone grafting.
AB  - PURPOSE: Extensive glenoid bone loss after failed shoulder arthroplasty
      represents a challenge for revision arthroplasty. Treatment options vary widely
      and have been a source of controversy among experts. METHODS: Between 2004 and
      2010, a total of 17 patients underwent glenoid reconstruction surgery using an
      autologous iliac crest bone graft and secondary revision arthroplasty due to
      extensive glenoid bone loss after failed previous total shoulder arthroplasty.
      The outcomes were assessed by means of clinical examination, Constant score, and
      bi-plane radiography as well as pre-, postoperative and follow-up CT. RESULTS:
      Before the revision surgery, the mean Constant score was 24 +/- 17 and improved
      to 40 +/- 13 after the glenoid rebuilding and revision arthroplasty. CT imaging
      revealed adequate glenoid bone stock restoration with no relevant graft
      resorption or loosening of the glenoid. The average postoperative antero
      posterior diameter of the glenoid was 28 +/- 3 mm which had decreased to 25 +/- 3
      mm at follow-up. The average postoperative version of the glenoid was 95.7
      degrees  +/- 6 degrees  and had decreased to 98.5 degrees  +/- 4 degrees  at
      follow-up. Both the glenoid version and diameter had changed significantly (P <
      0.001) comparing postoperative and follow-up CT-scans. CONCLUSION: Glenoid
      reconstruction surgery using an iliac crest bone-block autograft prior to
      revision arthroplasty represents a valuable salvage procedure in cases of
      extensive glenoid bone loss after primary shoulder arthroplasty. Sufficient
      glenoid bone stock restoration is indispensable for reliable fixation of glenoid
      components and in turn a satisfactory clinical outcome.

PMID- 24323350
TI  - Human evolution and tears of the rotator cuff.
AB  - PURPOSE: Humans differ from other great ape species in their propensity to
      develop tears of the rotator cuff. The aim of this study was to compare the
      anatomical risk factors for subacromial impingement and rotator cuff tears
      amongst the great apes and to determine which features may be accentuated in
      humans and therefore play a more significant role in disease aetiology. METHODS:
      Orthogonal digital photographs of 22 human, 17 gorilla, 13 chimpanzee and 12
      orangutan dry bone scapula specimens oriented in the glenoid plane were taken.
      Anatomical measurements were preformed using a calibrated digital image technique
      and the results scaled according to scapula vertebral border length. RESULTS: Of
      the ten anatomical features associated with subacromial impingement and rotator
      cuff tears in humans, none were shown to be accentuated and significantly
      different to the other species studied. However the human supraspinatus fossa was
      shown to be significantly smaller. CONCLUSIONS: These results indicate that an
      alternative primary aetiological factor for rotator cuff tears must exist. A
      reduction in the size of the supraspinatus fossa in human scapulae suggests that
      structural insufficiency of the supraspinatus or a change in rotator cuff force
      vectors could play a role.

PMID- 24323351
TI  - Ten year results of the collum femoris preserving total hip replacement: a
      prospective cohort study of seventy five patients.
AB  - PURPOSE: The collum femoris preserving (CFP) uncemented prosthesis has a bone
      preserving, high subcapital neck resection and a short anatomical stem. The ideal
      arthroplasty option in the younger, active patient is a subject of some debate.
      We evaluated midterm outcomes of the CFP in this patient population. METHODS: A
      prospective, consecutive cohort of 75 CFP total hip replacement (THR) patients
      with a mean age of 52 years was followed for a mean of 9.3 years. Patients were
      assessed using the Harris Hip Score (HHS). Pain was assessed using a visual
      analogue scale (VAS) and activity levels using the University of California, Los
      Angeles (UCLA) score. Radiographs were evaluated for evidence of loosening.
      Survivorship was calculated with an endpoint of revision for aseptic loosening or
      radiographic evidence of loosening. RESULTS: Mean HHS improved from a mean of 50
      pre-operatively to 91 (p < 0.001) postoperatively. Mean pain score was 1, mean
      patient satisfaction was 9 and mean UCLA score was 6. Two acetabular components
      were revised for aseptic loosening; no stem required revision. Radiographically,
      no cases had evidence of loosening. Survivorship was 96.8 % for the acetabular
      component and 100 % for the stem at ten years. Three patients died from unrelated
      causes, and five were lost to follow-up. CONCLUSIONS: Bone-preserving hip
      replacement has increased in popularity as hip replacement in younger and more
      active individuals increases. The CFP prosthesis has excellent midterm clinical
      function and survival and provides high levels of satisfaction in young patients.

PMID- 24323352
TI  - Supercharging allografts with mesenchymal stem cells in the operating room during
      hip revision.
AB  - PURPOSE: Bone marrow derived mesenchymal stem cells (BM-MSCs) have been proposed
      to improve allografts used during hip revision. However, no study has reported
      the number of MSCs that could be associated with the allograft and the best
      technique to load MSCs in allografts. The optimal loading technique should
      combine methods to increase the initial cell density and create an appropriate
      environment to accelerate the efficiency of the cell-allograft constructs into
      clinically applicable grafts. We designed a study to evaluate the number of MSCs
      in an autograft femoral head considered as the gold standard and to determine the
      best operating room procedure for loading in allograft with MSCs to approach the
      same number as in an autograft femoral head. Therefore this study explored a
      potential of charging whole femoral head allografts with autologous MSCs from
      iliac crest aspirate for hip revision procedures. METHODS: First, the study
      evaluated the total number of mesenchymal stem cells (MSCs) in 1 cc of an average
      autograft femoral head; this number then serves as a target for loading
      allografts, in order to achieve the same density of MSCs. For the loading
      technique itself, several questions were asked and hence several options were
      investigated. For example, is it better to load the whole allograft or break it
      up into several fragments? Which way of injecting works best for the whole
      femoral head allograft (through cartilage or femoral neck)? How concentrated (in
      terms of MSCs) should the injected iliac crest marrow be? Bone marrow for
      injection in allografts was obtained from residual marrow from patients
      undergoing surgical procedures with concentrated bone marrow. With this bone
      marrow (with and without concentration) we tested different techniques (injection
      and soaking) to load stem cells in allografts of different sizes: bulk
      allografts, pieces or blocks (8 or 1 cm(3) blocks) and morselized fragments (from
      125 to 8 mm(3)) or particules (1 mm(3)). We also evaluated the release of MSCs
      from fragments of autografts and allografts loaded with MSCs in cultured medium.
      RESULTS: The femoral head autografts contained a lower concentration of MSCs than
      the iliac crests of the same patient. However, in absence of concentration, with
      bone marrow aspirated from the iliac crest, we were not able to load in the
      femoral head allograft the same number of MSCs as the number present in an
      autograft. The loaded volume of bone marrow (and the corresponding number of
      MSCs) depended on the technique (injecting, soaking) as well as on the volume and
      shape of the allografts. The seeding efficiency of loading MSCs in allografts
      increased with the concentration of MSCs in the bone marrow. With concentrated
      bone marrow, supercharging the allograft with MSCs (as compared with an
      autograft) was possible in the operating room, and the number of MSCs
      supercharged in allografts was predictable. CONCLUSIONS: The loaded volume of
      bone marrow depended on the technique (injecting, soaking) as well as on the
      volume and shape of the allografts. With concentrated bone marrow, the allograft
      could be charged with a similar or higher number of MSCs than the number present
      in a femoral head autograft.

PMID- 24323353
TI  - Correlation between groin pain and cup design of hip-resurfacing implants: a
      prospective study.
AB  - PURPOSE: Cup design has been incriminated as the source of groin pain after hip
      resurfacing but has not been well described; thus, it was assessed in a
      prospective study looking at three implant types. METHODS: A group-match was done
      between three groups of hip resurfacing devices according to age, sex, body mass
      index, activity level, osteoarthritis aetiology and pre-operative scores.
      RESULTS: The global groin pain rate was 5.7 % at six months and 2.7 % at last
      follow-up. Groin pain rate was significantly different between the three groups
      (p = 0.004) and had a strong influence on the subjective results (p = 0.04). No
      groin pain emerged between six months and last follow-up. No clinical differences
      were noted in Harris hip score and Merle d'Aubigne-Postel score at last follow
      up. However, the Oxford hip score and Devane activity score were significantly
      lower for cups with macrostructures. CONCLUSION: The low groin pain rate in this
      prospective cohort was probably secondary to the specific surgical technique used
      and seems to be correlated with cup design. Macrostructures on the external part
      of the cup could be significantly harmful.

PMID- 24323354
TI  - A model for the water-oxidation and recovery systems of the oxygen-evolving
      complex.
AB  - We propose a model for the water-oxidation and recovery systems of the oxygen
      evolving complex (OEC) of the photosystem II (PSII) enzyme. The whole system is
      constructed from two catalytic cycles, conducted as a tandem reaction: (i) a
      water-oxidation loop uses cerium(IV) ammonium nitrate as an oxidant to activate a
      dimanganese complex for water-oxidation and thereby liberate a molecule of O2 and
      (ii) a recovery loop begins with photoinhibition of the dimanganese complex but
      then uses O2 to reactivate the manganese centre. The net result is a catalytic
      water-oxidation catalyst that can use self-generated O2 for recovery.

PMID- 24323355
TI  - Chemotherapy activates cancer-associated fibroblasts to maintain colorectal
      cancer-initiating cells by IL-17A.
AB  - Many solid cancers display cellular hierarchies with self-renewing, tumorigenic
      stemlike cells, or cancer-initiating cells (CICs) at the apex. Whereas CICs often
      exhibit relative resistance to conventional cancer therapies, they also receive
      critical maintenance cues from supportive stromal elements that also respond to
      cytotoxic therapies. To interrogate the interplay between chemotherapy and CICs,
      we investigated cellular heterogeneity in human colorectal cancers. Colorectal
      CICs were resistant to conventional chemotherapy in cell-autonomous assays, but
      CIC chemoresistance was also increased by cancer-associated fibroblasts (CAFs).
      Comparative analysis of matched colorectal cancer specimens from patients before
      and after cytotoxic treatment revealed a significant increase in CAFs.
      Chemotherapy-treated human CAFs promoted CIC self-renewal and in vivo tumor
      growth associated with increased secretion of specific cytokines and chemokines,
      including interleukin-17A (IL-17A). Exogenous IL-17A increased CIC self-renewal
      and invasion, and targeting IL-17A signaling impaired CIC growth. Notably, IL-17A
      was overexpressed by colorectal CAFs in response to chemotherapy with expression
      validated directly in patient-derived specimens without culture. These data
      suggest that chemotherapy induces remodeling of the tumor microenvironment to
      support the tumor cellular hierarchy through secreted factors. Incorporating
      simultaneous disruption of CIC mechanisms and interplay with the tumor
      microenvironment could optimize therapeutic targeting of cancer. 

PMID- 24323356
TI  - MHC class II-dependent B cell APC function is required for induction of CNS
      autoimmunity independent of myelin-specific antibodies.
AB  - Whether B cells serve as antigen-presenting cells (APCs) for activation of
      pathogenic T cells in the multiple sclerosis model experimental autoimmune
      encephalomyelitis (EAE) is unclear. To evaluate their role as APCs, we engineered
      mice selectively deficient in MHC II on B cells (B-MHC II(-/-)), and to
      distinguish this function from antibody production, we created transgenic (Tg)
      mice that express the myelin oligodendrocyte glycoprotein (MOG)-specific B cell
      receptor (BCR; IgH(MOG-mem)) but cannot secrete antibodies. B-MHC II(-/-) mice
      were resistant to EAE induced by recombinant human MOG (rhMOG), a T cell- and B
      cell-dependent autoantigen, and exhibited diminished Th1 and Th17 responses,
      suggesting a role for B cell APC function. In comparison, selective B cell IL-6
      deficiency reduced EAE susceptibility and Th17 responses alone. Administration of
      MOG-specific antibodies only partially restored EAE susceptibility in B-MHC II(-/
      ) mice. In the absence of antibodies, IgH(MOG-mem) mice, but not mice expressing
      a BCR of irrelevant specificity, were fully susceptible to acute rhMOG-induced
      EAE, also demonstrating the importance of BCR specificity. Spontaneous
      opticospinal EAE and meningeal follicle-like structures were observed in IgH(MOG
      mem) mice crossed with MOG-specific TCR Tg mice. Thus, B cells provide a critical
      cellular function in pathogenesis of central nervous system autoimmunity
      independent of their humoral involvement, findings which may be relevant to B
      cell-targeted therapies. 

PMID- 24323357
TI  - A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic
      dermatitis.
AB  - Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for
      their development. We show that human ILC2s express skin homing receptors and
      infiltrate the skin after allergen challenge, where they produce the type 2
      cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2,
      which is up-regulated during activation, and are enriched in lesional skin
      biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and
      amphiregulin expression, and increases ILC2 migration. Furthermore, we
      demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and
      IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic
      of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2
      may contribute to increases in type 2 cytokine production in the absence of the
      suppressive E-cadherin ligation through this novel mechanism of barrier sensing.
      Using Rag1(-/-) and RORalpha-deficient mice, we confirm that ILC2s are present in
      mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant
      ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their
      production of type 2 cytokines in response to IL-33, identifies a role for ILC2s
      in the pathogenesis of cutaneous atopic disease. 

PMID- 24323358
TI  - KIT oncogene inhibition drives intratumoral macrophage M2 polarization.
AB  - Tumor-associated macrophages (TAMs) are a major component of the cancer
      microenvironment. Modulation of TAMs is under intense investigation because they
      are thought to be nearly always of the M2 subtype, which supports tumor growth.
      Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and
      typically results from an activating mutation in the KIT oncogene. Using a
      spontaneous mouse model of GIST and 57 freshly procured human GISTs, we
      discovered that TAMs displayed an M1-like phenotype and function at baseline. In
      both mice and humans, the KIT oncoprotein inhibitor imatinib polarized TAMs to
      become M2-like, a process which involved TAM interaction with apoptotic tumor
      cells leading to the induction of CCAAT/enhancer binding protein (C/EBP)
      transcription factors. In human GISTs that eventually developed resistance to
      imatinib, TAMs reverted to an M1-like phenotype and had a similar gene expression
      profile as TAMs from untreated human GISTs. Therefore, TAM polarization depends
      on tumor cell oncogene activity and has important implications for
      immunotherapeutic strategies in human cancers. 

PMID- 24323359
TI  - IRF4 controls the positioning of mature B cells in the lymphoid microenvironments
      by regulating NOTCH2 expression and activity.
AB  - The transcription factor interferon regulatory factor-4 (IRF4) is expressed in B
      cells at most developmental stages. In antigen-activated B cells, IRF4 controls
      germinal center formation, class-switch recombination, and the generation of
      plasma cells. Here we describe a novel function for IRF4 in the homeostasis of
      mature B cells. Inducible deletion of irf4 specifically in B cells in vivo led to
      the aberrant accumulation of irf4-deleted follicular B cells in the marginal zone
      (MZ) area. IRF4-deficient B cells showed elevated protein expression and
      activation of NOTCH2, a transmembrane receptor and transcriptional regulator
      known to be required for MZ B cell development. Administration of a NOTCH2
      inhibitory antibody abolished nuclear translocation of NOTCH2 in B cells within
      12 h and caused a rapid and progressive disintegration of the MZ that was
      virtually complete 48 h after injection. The disappearance of the MZ was
      accompanied by a transient increase of MZ-like B cells in the blood rather than
      increased B cell apoptosis, demonstrating that continued NOTCH2 activation is
      critical for the retention of B cells in the MZ. Our results suggest that IRF4
      controls the positioning of mature B cells in the lymphoid microenvironments by
      regulating NOTCH2 expression. These findings may have implications for the
      understanding of B cell malignancies with dysregulated IRF4 and NOTCH2 activity. 

PMID- 24323360
TI  - Zebularine significantly sensitises MEC1 cells to external irradiation and
      radiopharmaceutical therapy when administered sequentially in vitro.
AB  - Zebularine is a cytidine analogue incorporated into DNA during replication,
      inhibiting DNA methyltransferase 1 (DNMT1), resulting in demethylation and
      changes in gene expression. Such modification may improve radiosensitivity in
      resistant lymphoma cells. The hypothesis of this study was that zebularine and
      radiation would synergistically inhibit cell growth and viability. Human MEC1
      malignant B cells were incubated with 0-200 uM zebularine for 48 h. Media
      containing zebularine was removed, and the cells were irradiated with 0-2 Gy of
      either external beam irradiation or (177) Lu-DOTA-TATE, a radiolabelled
      somatostatin analogue. Concentration and viability were measured over 48-72 h.
      The proportion of apoptotic cells was identified using an active Caspase 3/7
      assay. Zebularine inhibited growth of cells in a dose-dependent manner during
      exposure. No residual growth inhibition occurred following removal of the drug.
      Zebularine and external irradiation inhibited cell proliferation in a dose
      dependent, synergistic interaction, but the effect on viability was additive.
      Treatment with zebularine and (177) Lu-DOTA-TATE resulted in less inhibition of
      proliferation (P = 0.0135), but a synergistic decrease in viability. Apoptotic
      fraction was much higher in cells irradiated with (177) Lu-DOTA-TATE than
      external irradiation. External irradiation induces growth arrest rather than
      apoptosis. Apoptosis is the primary effect of radiopharmaceutical therapy on
      tumour cells. Treatment with the methylation inhibitor, zebularine, appears to
      synergistically augment these natural effects in vitro, which could be exploited
      clinically.

PMID- 24323361
TI  - Influence of terminal differentiation and PACAP on the cytokine, chemokine, and
      growth factor secretion of mammary epithelial cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with
      trophic and cytoprotective effects, has been shown to affect cell survival,
      proliferation, and also differentiation of various cell types. The high PACAP
      level in the milk and its changes during lactation suggest a possible effect of
      PACAP on the differentiation of mammary epithelial cells. Mammary cell
      differentiation is regulated by hormones, growth factors, cytokines/chemokines,
      and angiogenic proteins. In this study, differentiation was hormonally induced by
      lactogenic hormones in confluent cultures of HC11 mouse mammary epithelial cells.
      We investigated the effect of PACAP on mammary cell differentiation as well as
      release of cytokines, chemokines, and growth factors. Differentiation was
      assessed by expression analysis of the milk protein beta-casein. Differentiation
      significantly decreased the secretion of interferon gammainduced protein (IP)-10,
      "regulated upon activation normal T cell expressed and presumably secreted"
      (RANTES), insulin-like growth factor-binding protein (IGFBP)-3 and the epidermal
      growth factor receptor (EGFR) ligands, such as epidermal growth factor (EGF) and
      amphiregulin (AREG). The changes in the levels of IP-10 and RANTES may be
      relevant for the alterations in homing of T cells and B cells at different stages
      of mammary gland development, while the changes of the EGFR ligands may
      facilitate the switch from proliferative to lactating stage. PACAP did not
      modulate the expression of beta-casein or the activity of hormone-induced
      pathways as determined by the analysis of phosphorylation of Akt, STAT5, and p38
      MAPK. However, PACAP decreased the release of EGF and AREG from non
      differentiated cells. This may influence the extracellular signal-related
      transactivation of EGFR in the non-differentiated mammary epithelium and is
      considered to have an impact on the modulation of oncogenic EGFR signaling in
      breast cancer. 

PMID- 24323363
TI  - Reciprocal relations between coalition functioning and the provision of
      implementation support.
AB  - Community coalitions have been promoted as a strategy to help overcome challenges
      to the dissemination and implementation of evidence-based prevention programs.
      This paper explores the characteristics of coalitions that enable the provision
      of implementation support for prevention programs in general and for the
      implementation of evidence-based prevention programs with fidelity. Longitudinal
      cross-lagged panel models were used to study 74 Communities That Care (CTC)
      coalitions in Pennsylvania. These analyses provide evidence of a unidirectional
      influence of coalition functioning on the provision of implementation support.
      Coalition member knowledge of the CTC model best predicted the coalition's
      provision of support for evidence-based program implementation with fidelity.
      Implications for developing and testing innovative methods for delivering
      training and technical assistance to enhance coalition member knowledge are
      discussed. 

PMID- 24323364
TI  - What is below the support layer affects carbon nanotube growth: an iron catalyst
      reservoir yields taller nanotube carpets.
AB  - Here we demonstrate an approach to enhance the growth of vertically aligned
      carbon nanotubes (CNTs) by including a catalyst reservoir underneath the thin
      film alumina catalyst underlayer. This reservoir led to enhanced CNT growth due
      to the migration of catalytic material from below the underlayer up to the
      surface through alumina pinholes during processing. This led to the formation of
      large Fe particles, which in turn influenced the morphology evolution of the
      catalytic iron surface layer through Ostwald ripening. With inclusion of this
      catalyst reservoir, we observed CNT growth up to 100% taller than that observed
      without the catalyst reservoir consistently across a wide range of annealing and
      growth durations. Imaging studies of catalyst layers both for different annealing
      times and for different alumina support layer thicknesses demonstrate that the
      surface exposure of metal from the reservoir leads to an active population of
      smaller catalyst particles upon annealing as opposed to a bimodal catalyst size
      distribution that appears without inclusion of a reservoir. Overall, the
      mechanism for growth enhancement we present here demonstrates a new route to
      engineering efficient catalyst structures to overcome the limitations of CNT
      growth processes. 

PMID- 24323362
TI  - UCH-L1 inhibition involved in CREB dephosphorylation in hippocampal slices.
AB  - Ubiquitin C-terminal hydrolase L1 (UCH-L1) is abundantly expressed in the brain
      and is critical for the normal function of synapses. cAMP response element
      binding protein (CREB) is a transcription factor which initiates the expression
      of proteins that related to the regulation of synaptic plasticity and memory
      function. Studies have shown that UCH-L1 can influence the expression and
      activity of CREB, but the underlying mechanisms remain unclear. In this study, we
      used UCH-L1 inhibitor LDN to treat mice hippocampal slices and found that UCH-L1
      inhibition caused the dephosphorylation of CREB at Ser133 site. Meanwhile,
      hyperphosphorylation of microtubule-associated protein tau; increased expression
      of synaptic protein components of PSD-95 and synapsin-1, and decreased activity
      of tyrosine kinase Fyn were observed after UCH-L1 inhibition. Moreover, all these
      alternations have an influence on the normal function of N-methyl-D-aspartate
      (NMDA) receptor NR2B subunit which is likely to result in the dephosphorylation
      of CREB. We also found that LDN treatment mediated protein kinase A (PKA)
      deactivation was involved in the dephosphorylation of CREB. Thus, our study
      introduces a novel possible mechanism for elaborating the effects of UCH-L1
      inhibition on the CREB activity and the implicated signaling pathways. 

PMID- 24323365
TI  - Outcomes associated with balloon angioplasty for recurrent coarctation in
      neonatal univentricular and biventricular norwood-type aortic arch
      reconstructions.
AB  - OBJECTIVES: We evaluated the use of, and outcomes associated with, balloon
      angioplasty (BA) for recurrent coarctation in single ventricle (SV) and two
      ventricle (2V) patients following a Norwood-type aortic arch reconstruction
      (NTAR). BACKGROUND: Extended patch augmentation of the aorta, a NTAR, is utilized
      in SV patients undergoing the Norwood procedure (NP) as well as 2V patients with
      a diffusely hypoplastic aorta. While many studies have evaluated recurrent
      coarctation following the NP, the incidence of recurrent coarctation and outcomes
      associated with BA in 2V patients following NTAR are unclear. METHODS: A
      retrospective review was performed of all neonates who underwent a NTAR at our
      institution between 2000 and 2010. The incidence of recurrent coarctation
      requiring intervention and factors associated with successful BA were evaluated.
      RESULTS: A NTAR was performed in 361 SV patients and 88 2V patients. The
      incidence of recurrent coarctation requiring intervention was 19.3% in 2V vs.
      9.7% in SV patients (P = 0.01) at a median of 0.5 (interquartile range 0.3-1.2)
      years from initial surgery. BA was successful in 25 SV patients (81%) and 10 2V
      patients (71%; P = 0.70). Of the characteristics evaluated, lower initial peak-to
      peak gradient (P = 0.02), larger balloon size for angioplasty (P = 0.02) and
      larger diameter of the descending aorta (P = 0.01) were associated with BA
      success. CONCLUSIONS: Recurrent coarctation following NTAR is more common in 2V
      patients than in SV patients. BA for recurrent coarctation has similar success in
      both groups and should continue to be utilized in this population.

PMID- 24323366
TI  - The effect on rat embryonic heart rate of Na+, K+, and Ca2+ channel blockers, and
      the human teratogen phenytoin, changes with gestational age.
AB  - In this study, we compared the effects of four ion channel blockers on rat
      embryonic heart function during the organogenic period from gestational day (GD)
      10 to 15, to determine the changes in dependence on ion channels during rat
      cardiac development. Rat embryos in culture were exposed to either the human
      ether-a-go-go-related gene potassium channel blocker, dofetilide (400 nM); the
      sodium channel blocker, lidocaine (250 MUM); the L-type calcium channel blocker,
      nifedipine (1.8 MUM); or the multichannel blocker, phenytoin (200 MUM). Lidocaine
      slowed the heart rate (HR) with the effect becoming more severe with increasing
      GD. Dofetilide slowed the embryonic HR and caused arrhythmias with the most
      severe effect on GD 11 to 13. Nifedipine primarily caused a negative inotropic
      effect except on GD 10 when it stopped the heart in most embryos. Phenytoin
      stopped the heart of most GD 10 to 12 embryos while on GD 13 to 15 phenytoin
      slowed the heart. The results demonstrate that as the rat heart develops during
      the organogenic period its functional dependence on ion channels changes
      markedly. These changes are important for understanding drug effects on the
      embryo during pregnancy and the methodology used provides a simple procedure for
      assessing drug effects on the developing heart. 

PMID- 24323368
TI  - Predictive genetic testing, risk communication, and risk perception: an
      international expert meeting in Berlin, Germany.

PMID- 24323367
TI  - Regulation of cancer metabolism by O-GlcNAcylation.
AB  - Cancer cells exhibit increased uptake of glucose and glutamine, and rewire the
      metabolic flux toward anabolic pathways important for cell growth and
      proliferation. Understanding how this altered metabolism is regulated has
      recently emerged as an intense research focus in cancer biology. O-linked beta-N
      acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification of
      serine and/or threonine residues of nuclear and cytosolic proteins. O
      GlcNAcylation has been identified in numerous proteins that are involved in many
      important cellular functions, including transcription, translation, signal
      transduction, and stress responses. More recently, increasing evidence indicates
      that O-GlcNAcylation plays important roles in regulating cancer metabolic
      reprogramming by modifying key transcription factors, metabolic enzymes and major
      oncogenic signaling pathways. Thus, O-GlcNAcylation emerges as a novel regulatory
      mechanism linking altered metabolism to cancer pathogenesis. 

PMID- 24323370
TI  - Re-analysis of safety data supporting doxylamine use for nausea and vomiting of
      pregnancy.
AB  - Antihistamines are commonly used to treat nausea and vomiting of pregnancy (NVP).
      We re-analyzed the 24 primary studies cited in a 1997 meta-analysis that
      concluded antihistamine use for NVP was safe as they had been studied in more
      than 200,000 participating women and the pooled odds ratio for congenital
      malformations was 0.76 (95% confidence interval [CI]: 0.60-0.94). Our analysis of
      this meta-analysis showed that 139,414 women were included in 22 original studies
      involving antihistamines, 129,108 of which were in studies involving doxylamine.
      In these studies, 23,485 women were exposed to antihistamines, 14,624 of which
      were exposed to doxylamine. The summary relative risk (cohort studies) and odds
      ratio (case-control studies) for congenital malformations from antihistamine
      exposure were 1.09 (95% CI: 1.01-1.18) and 1.04 (95% CI: 0.91-1.19), and for
      doxylamine exposure, the summary relative risk and odds ratio were 0.94 (95% CI:
      0.80-1.10) and 1.07 (95% CI: 0.93-1.23), respectively. Although not a new
      systematic review, our re-analysis demonstrates that the safety data for
      antihistamines, and doxylamine in particular, are based on many fewer than
      200,000 participating women and exposures, and that doxylamine use is not
      associated with a decreased risk of malformations as previously reported. 

PMID- 24323372
TI  - LC-MS/MS method for the characterization of the forced degradation products of
      Entecavir.
AB  - A rapid, specific, and reliable isocratic LC-MS/MS method has been developed and
      validated for the identification and characterization of the stressed degradation
      products of Entecavir (ETV). ETV, an antiviral drug, was subjected to hydrolysis
      (acidic, alkaline, and neutral), oxidation, photolysis and thermal stress, as per
      the international conference on harmonization specified conditions. The drug
      showed extensive degradation under oxidative and acid hydrolysis stress
      conditions. However, it was stable to thermal, acidic, neutral, and photolysis
      stress conditions. A total of five degradation products were observed and the
      chromatographic separation of the drug and its degradation products were achieved
      on a Waters Symmetry C18 (250 mm * 4.6 mm, id, 5 MUm) column using 20 mM ammonium
      acetate (pH 3)/acetonitrile (50:50, v/v) as a mobile phase. The degradation
      products were characterized by LC-MS/MS and its fragmentation pathways were
      proposed. The LC-MS method was validated with respect to specificity, linearity,
      accuracy, and precision. No previous reports were found in the literature
      regarding the degradation behavior of ETV. 

PMID- 24323371
TI  - Health status and 6 years survival of 552 90+ Italian sib-ships recruited within
      the EU Project GEHA (GEnetics of Healthy Ageing).
AB  - In a scenario of increasing life expectancy worldwide, it is mandatory to
      identify the characteristics of a healthy aging phenotype, including survival
      predictors, and to disentangle those related to environment/lifestyle versus
      those related to familiarity/genetics. To this aim we comprehensively
      characterised a cohort of 1,160 Italian subjects of 90 years and over (90+, mean
      age 93 years; age range 90-106 years) followed for 6 years survival, belonging to
      552 sib-ships (familiar longevity) recruited (2005-2008) within the EU-funded
      GEHA project in three Italian geographic areas (Northern, Central and Southern
      Italy) different for urban/rural and socio-economical characteristics. On the
      whole, the following factors emerged as significant predictors of survival after
      90 years of age: absence of cognitive impairment and physical disability, high
      hand grip strength scores and body mass index (BMI) values, "excellent/good" self
      reported health, high haemoglobin and total cholesterol levels and low creatinine
      levels. These parameters, excluding BMI values, were also significantly
      associated within sib-ships, suggesting a strong familial/genetic component.
      Geographical micro-heterogeneity of survival predictors emerged, such as
      functional and physical status being more important in Southern than in Central
      and Northern Italy. In conclusion, we identified modifiable survival predictors
      related to specific domains, whose role and importance vary according to the
      geographic area considered and which can help in interpreting the genetic results
      obtained by the GEHA project, whose major aim is the comprehensive evaluation of
      phenotypic and genetic data. 

PMID- 24323373
TI  - A rapid flow cytometry assay for the relative quantification of protein
      encapsulation into bacterial microcompartments.
AB  - Bacterial microcompartments (MCPs) are protein-based organelles that have been
      suggested as scaffolds for creating in vivo nanobioreactors. One of the key steps
      towards engineering MCPs is to understand and maximize the encapsulation of
      enzymes into the lumen of the MCP. However, there are currently no high
      throughput methods for investigating protein encapsulation. Here, we describe the
      development of a rapid in vivo assay for quantifying the relative amount of
      protein encapsulated within MCPs based on fluorescence. In this assay, we fuse a
      degradation peptide to a MCP-targeted fluorescence reporter and use flow
      cytometry to measure overall fluorescence from the encapsulated, protected
      reporter protein. Using this assay, we characterized various MCP-targeting signal
      sequence mutants for their ability to encapsulate proteins and identified mutants
      that encapsulate a greater amount of protein than the wild type signal sequence.
      This assay is a powerful tool for reporting protein encapsulation and is an
      important step towards encapsulating metabolic enzymes into MCPs for synthetic
      biochemical pathways. 

PMID- 24323374
TI  - Interaction between vWF levels and aspirin resistance in ischemic stroke
      patients.
AB  - The von Willebrand factor (vWF) levels increase in acute-phase ischemic stroke
      because of endothelial dysfunction and thrombus formation and may reduce
      acetylsalicylic acid (ASA) efficiency in hemostatic cascade. The aim of the study
      is to investigate the relationship between vWF levels and ASA resistance in
      ischemic stroke patients. Fifty acute ischemic stroke patients (mean age 66.3+/
      13 years, 34 males) were given 300 mg/day aspirin for at least 10 days, and 25
      healthy volunteers as a control group were compared using platelet function
      analyzer-100 test. All risk factors were investigated for a correlation to ASA
      resistance. ASA resistance was apparent in 32% of the study group and in 20% of
      the control group (p=0.140). vWF levels were elevated in only ASA nonresponders
      and the ischemic stroke group that showed a statistically significant association
      with aspirin resistance (p<=0.05). vWF levels increase in ASA nonresponders and
      ischemic stroke group in acute phase. High vWF levels may relate to ASA
      resistance and recurrent strokes.

PMID- 24323375
TI  - Heart rate variability in stroke patients submitted to an acute bout of aerobic
      exercise.
AB  - Stroke has been associated with cardiac autonomic impairment due to damage in
      central nervous system. Dysfunction in heart rate variability (HRV) may reflect
      dysfunction of the autonomic nervous system. Aerobic training has been used in
      the rehabilitation procedure of patients, due to improvement of aerobic function
      and other beneficial effects as increased recruitment of motor units, favoring
      the development of muscle fibers. The purpose of this study was to evaluate the
      cardiac autonomic modulation in patients with stroke before, during, and after an
      acute bout of aerobic exercise. The heart rate of 38 stroke patients was recorded
      using a heart rate (HR) monitor and the data were used to assess cardiac
      autonomic modulation through HRV analysis. The patients were in supine position
      and remained at resting condition (R) for 10 min before starting the experiment.
      Afterwards, they were submitted to walking exercise (E) on a treadmill until
      achieve 50-70% of maximum heart rate. After 30 min of aerobic exercise, the
      subjects were advised to remain in supine position for additional 30 min in order
      to record the HR during the recovery (RC) period. The recordings were divided in
      three periods: RC1, immediately after the end of exercise bout, RC2, between 12
      and 17 min of recovery, and RC3, at the final 5 min of recovery. A significant
      decrease was observed during exercise in the MeanRR index (577.3+/-92 vs.
      861.1+109), RRtri (5.1+/-2 vs. 9.1+/-3), high frequency component (11.2+/-4 vs.
      167+/-135 ms) and SD1 (5.7+/-2 vs. 16.9+/-7 ms) compared to resting values. The
      SDNN index reduced during E (27.6+/-19) and RC1 (29.9+/-11), RC2 (27.9+/-9) and
      RC3 (32.4+/-13) compared to resting values (42.4+/-19). The low frequency
      component increased during E (545+/-82), but decreased during RC1 (166.3+/-129),
      RC2 (206.9+/-152), and RC3 (249.5+/-236) compared to R levels (394.6+/-315).
      These findings suggest that stroke patients showed a reduced HRV during and at
      least 30 min after exercise, due to an autonomic imbalance reflected by increased
      indexes that represent the sympathetic nervous system.

PMID- 24323376
TI  - Dynamic contrast-enhanced MRI evaluation of cerebral cavernous malformations.
AB  - The aim of this study is to quantitatively evaluate the behavior of CNS cavernous
      malformations (CCMs) using a dynamic contrast-enhanced MRI (DCEMRI) technique
      sensitive for slow transfer rates of gadolinium. The prospective study was
      approved by the institutional review board and was HIPPA compliant. Written
      informed consent was obtained from 14 subjects with familial CCMs (4 men and 10
      women, ages 22-76 years, mean 48.1 years). Following routine anatomic MRI of the
      brain, DCEMRI was performed for six slices, using T1 mapping with partial
      inversion recovery (TAPIR) to calculate T1 values, following administration of
      0.025 mmol/kg gadolinium DTPA. The transfer rate (Ki) was calculated using the
      Patlak model, and Ki within CCMs was compared to normal-appearing white matter as
      well as to 17 normal control subjects previously studied. All subjects had
      typical MRI appearance of CCMs. Thirty-nine CCMs were studied using DCEMRI. Ki
      was low or normal in 12 lesions and elevated from 1.4 to 12 times higher than
      background in the remaining 27 lesions. Ki ranged from 2.1E-6 to 9.63E-4 min(-1),
      mean 3.55E-4. Normal-appearing white matter in the CCM patients had a mean Ki of
      1.57E-4, not statistically different from mean WM Ki of 1.47E-4 in controls.
      TAPIR-based DCEMRI technique permits quantifiable assessment of CCMs in vivo and
      reveals considerable differences not seen with conventional MRI. Potential
      applications include correlation with biologic behavior such as lesion growth or
      hemorrage, and measurement of drug effects. 

PMID- 24323377
TI  - Transgene delivery to endothelial cultures derived from porcine carotid artery ex
      vivo.
AB  - Carotid artery disease is a widespread cause of morbidity and mortality. Porcine
      models of vascular disease are well established in vivo, but existing endothelial
      systems in vitro (e.g. human umbilical vein endothelial cells, rat aortic
      endothelial cultures) poorly reflect carotid endothelium. A reliable in vitro
      assay would improve design of in vivo experiments and allow reduction and
      refinement of animal use. This study aimed (1) to develop ex vivo endothelial
      cultures from porcine carotid and (2) to test whether these were suitable for
      lentivector-mediated transgene delivery. Surplus carotid arteries were harvested
      from young adult female Large White pigs within 10 min post-mortem. Small sectors
      of carotid artery wall (approximately 4 mm*4 mm squares) were immobilised in a
      stable gel matrix. Cultures were exposed to HIV-derived lentivector (LV) encoding
      a reporter transgene or the equivalent integration-deficient vector (IDLV). After
      7-14 days in vitro, cultures were fixed and labelled histochemically. Thread-like
      multicellular outgrowths were observed that were positive for endothelial cell
      markers (CD31, VEGFR2, von Willebrand factor). A minority of cells co-labelled
      for smooth muscle markers. Sensitivity to cytotoxic agents (paclitaxel,
      cycloheximide, staurosporine) was comparable to that in cell cultures, indicating
      that the gel matrix permits diffusive access of small pharmacological molecules.
      Transgene-expressing cells were more abundant following exposure to LV than IDLV
      (4.7, 0.1% of cells, respectively). In conclusion, ex vivo adult porcine carotid
      artery produced endothelial cell outgrowths that were effectively transduced by
      LV. This system will facilitate translation of novel therapies to clinical
      trials, with reduction and refinement of in vivo experiments.

PMID- 24323378
TI  - Perlecan domain V is neuroprotective and affords functional improvement in a
      photothrombotic stroke model in young and aged mice.
AB  - With the failure of so many pre-clinical stroke studies to translate into the
      clinic, there is a need to find new therapeutics to minimize the extent of
      cellular damage and aid in functional recovery. Domain V (DV), the c-terminal
      protein fragment of the vascular basement membrane component, perlecan, was
      recently shown to afford significant protection in multiple transient middle
      cerebral artery occlusion stroke models. We sought here to determine whether DV
      might have similar therapeutic properties in a focal photothrombosis stroke model
      in both young and aged mice. Young (3-month old) and aged (24-month old) mice
      underwent photothrombotic stroke to the motor cortex and were then treated with
      DV or phosphate buffered saline vehicle at different initial time points up to 7
      days. Stroke volume was analyzed histologically using cresyl violet and
      functional recovery assessed behaviorally on both the grid-walking and cylinder
      tasks. In young mice, DV administration resulted in a significant decrease in
      infarct volume when treatment started 3 or 6 h post-stroke. In aged mice, DV
      administration was only protective when started 3 h post-stroke. In addition to a
      decrease in the area of infarction, DV treatment was effective in significantly
      decreasing the number of foot-faults on the grid-walking task and improving use
      of the stroke-affected limb in the cylinder task in both young and aged.
      Previously, we have shown that DV can alter the expression profile of various
      astroglial markers. Consistent with our previous finding, treatment groups that
      showed therapeutic potential in both young and aged mice also showed an elevation
      in glial fibrillary acidic protein (GFAP) expression in peri-infarct regions. We
      conclude that DV is neuroprotective and affords significant improvements in
      functional recovery in both young and aged mice after focal ischemia. These data
      also highlight a therapeutic time-window shift that is narrower in aged compared
      with young mice and is associated with an elevation in GFAP expression and
      heightened astrogliosis. 

PMID- 24323379
TI  - A model of rat embolic cerebral infarction with a quantifiable, autologous
      arterial blood clot.
AB  - We developed a novel model of a rat embolic cerebral infarction with a
      quantifiable autologous arterial blood clot. The left femoral artery had 0.15 ml
      of blood withdrawn and mixed with 10 units of thrombin in 50 MUl saline. After 30
      min, the clot was suctioned into a 4-French polyvinyl chloride tube. A 24-gage
      catheter was inserted up through the internal carotid artery via the external
      carotid artery stump. The 1-cm clot, at a volume of 7.2 mm3, was pushed and
      inserted into the internal carotid artery via the catheter. After withdrawing the
      catheter, the ICA blood flow recovered. We checked neurological status after 24 h
      (neurological free was 15, and worst was 1) and measured the infarction volume by
      the TTC method. Twelve rats were examined, and five sham-operated rats were
      included. Two rats were not able to achieve an 80% reduction in CBF. One rat died
      due to cerebral infarction. The success rate in producing infarction was 83%. The
      total infarction volume was 368.5 mm3+/-61.2 se. Median neurological score was 6.
      Hemorrhagic transformation was not detected. Sham-operated rats revealed no
      infarction and no neurological deficit. The volume of infarction correlated
      significantly with the neurological score. We conclude that this embolic stroke
      model is useful in producing a human, severe cardioembolic cerebral infarction.

PMID- 24323380
TI  - Psychosis improved dysphonia.
AB  - We present the case of a 40-year-old single man with a diagnosis of
      Schizoaffective Disorder since 1989 and a comorbid diagnosis of functional
      (dissociative) dysphonia since 2011. Although receiving ongoing treatment from a
      Speech and Language Therapist, the patient's symptoms of dysphonia have remained
      prominent from the time of diagnosis in 2011 and have been particularly apparent
      during times of psychosocial and interpersonal stress. He had a dramatic and
      complete resolution of all dysphonic symptoms during an acute relapse of the
      psychosis in February 2013 and experienced a gradual re-emergence of dysphonic
      symptoms when his episode of psychosis resolved. This is the first case report to
      demonstrate such an association and we discuss potential mechanisms for the
      resolution of dysphonic symptoms during this psychotic relapse. 

PMID- 24323381
TI  - Traumatic orbital CSF leak.
AB  - Compared to the cerebrospinalfluid (CSF) leak through the nose and ear, the
      orbital CSF leak is a rare and underreported condition following head trauma. We
      present the case of a 49-year-old woman with oedematous eyelid swelling and
      ecchymosis after a seemingly trivial fall onto the right orbit. Apart from the
      above, she was clinically unremarkable. The CT scan revealed a minimally
      displaced fracture of the orbital roof with no emphysema or intracranial
      bleeding. The fractured orbital roof in combination with the oedematous eyelid
      swelling raised the suspicion for orbital CSF leak. The MRI of the neurocranium
      demonstrated a small-sized CSF fistula extending from the anterior cranial fossa
      to the right orbit. The patient was treated conservatively and the lid swelling
      resolved completely after 5 days. Although rare, orbital CSF leak needs to be
      included in the differential diagnosis of periorbital swelling following orbital
      trauma. 

PMID- 24323382
TI  - Occurrence and removal of free and conjugated estrogens in wastewater and sludge
      in five sewage treatment plants.
AB  - The occurrence and fate of free and conjugated estrogens were investigated in
      wastewater and sludge from five sewage treatment plants (STPs) in Guangdong
      Province, China. Estrone (E1) and 17beta-estradiol (E2) were found in all
      influent samples at concentrations of 69.3-280 ng L(-1) and 1.3-30 ng L(-1),
      respectively. The concentrations of conjugated estrogens were from ND (not
      detected) to 7.6 ng L(-1). High concentrations (27.6-235 ng g(-1)) of E1 were
      found in sludge of some STPs indicating that sorption was an important estrogen
      removal mechanism. According to the mass flux analyses for estrogens in STP-A, E2
      was mainly removed in the anaerobic process and E1 removal was the combined
      efforts of biodegradation and sorption. Abnormally high concentrations of EE2
      (42.6-246 ng L(-1)), detected with gas chromatography-mass spectrometry, were
      found in all influent samples of the STPs, therefore interlaboratory analysis
      with liquid chromatography-tandem mass spectrometry was conducted for
      confirmation, which detected no EE2 at all. In consideration of the rather lower
      estimated EE2 concentration than the measured value, it was speculated that the
      presence of interfering substances like tetracosanic acid in the matrix could
      lead to overestimation of EE2 concentration. Overall, the effluents still pose
      potential estrogenic effect to the downstream aquatic organisms. 

PMID- 24323383
TI  - Ecosystem services provided by agroecosystems: a qualitative and quantitative
      assessment of this relationship in the Pampa region, Argentina.
AB  - The development of an analytical framework relating agricultural conditions and
      ecosystem services (ES) provision could be very useful for developing land-use
      systems which sustain natural resources for future use. According to this, a
      conceptual network was developed, based on literature review and expert
      knowledge, about the functional relationships between agricultural management and
      ES provision in the Pampa region (Argentina). We selected eight ES to develop
      this conceptual network: (1) carbon (C) balance, (2) nitrogen (N) balance, (3)
      groundwater contamination control, (4) soil water balance, (5) soil structural
      maintenance, (6) N2O emission control, (7) regulation of biotic adversities, and
      (8) biodiversity maintenance. This conceptual network revealed a high degree of
      interdependence among ES provided by Pampean agroecosystems, finding two trade
      offs, and two synergies among them. Then, we analyzed the conceptual network
      structure, and found that both environmental and management variables influenced
      ES provision. Finally, we selected four ES to parameterize and quantify along 10
      growing seasons (2000/2001-2009/2010) through a probabilistic methodology called
      Bayesian Networks. Only N balance was negatively impacted by agricultural
      management; while C balance, groundwater contamination control, and N2O emission
      control were not. Outcomes of our work emphasize the idea that qualitative and
      quantitative methodologies should be implemented together to assess ES provision
      in Pampean agroecosystems, as well as in other agricultural systems. 

PMID- 24323390
TI  - Barriers and challenges to global clinical cancer research.
AB  - BACKGROUND: There are concerns about growing barriers to cancer research. We
      explored the characteristics of and barriers to global clinical cancer research.
      METHODS: The American Society of Clinical Oncology International Affairs
      Committee invited 300 selected oncologists with research experience from 25
      countries to complete a Web-based survey. Fisher's exact test was used to compare
      answers between participants from high-income countries (HICs) and low- and
      middle-income countries (LMICs). Barriers to clinical cancer research were ranked
      from 1 (most important) to 8 (least important). Mann-Whitney's nonparametric test
      was used to compare the ranks describing the importance of investigated
      obstacles. RESULTS: Eighty oncologists responded, 41 from HICs and 39 from LMICs.
      Most responders were medical oncologists (62%) at academic hospitals (90%).
      Researchers from HICs were more involved with academic and industry-driven
      research than were researchers from LMICs. Significantly higher proportions of
      those who considered their ability to conduct academic research and industry
      driven research over the past 5 years more difficult were from HICs (73% vs. 27%
      and 70% vs. 30%, respectively). Concerning academic clinical cancer research, a
      lack of funding was ranked the most important (score: 3.16) barrier, without
      significant differences observed between HICs and LMICs. Lack of time or
      competing priorities and procedures from competent authorities were the second
      most important barriers to conducting academic clinical research in HICs and
      LMICs, respectively. CONCLUSION: Lack of funding, lack of time and competing
      priorities, and procedures from competent authorities might be the main global
      barriers to academic clinical cancer research.

PMID- 24323391
TI  - The importance of wound biopsy in the accurate diagnosis of acral malignant
      melanoma presenting as a foot ulcer.
AB  - Neoplastic changes arising at the sites of chronic, nonhealing wounds are not
      uncommon; however, they often go undiagnosed. We report a case of rapidly
      progressing plantar melanoma presenting as a chronic, nonhealing ulcer. A 46-year
      old patient presented at a specialized Wound Healing Center with an enlarging
      painful ulcer on the right heel of 3 months duration. The wound was biopsied and
      specimens were sent for examination at the Wound Pathology service at the
      Department of Dermatology and Cutaneous Surgery, University of Miami. Histology
      demonstrated features consistent with acral malignant melanoma.
      Immunohistochemistry using melanocytic markers MART-1, S-100, HMB-45 revealed
      positive staining indicating the presence of malignant cells, and D2-40 staining
      showed lymphatic invasion of the tumor in the wound biopsy specimen. The case
      presented here underscores the importance of wound biopsying in the diagnosis of
      malignancies associated with nonhealing wounds. 

PMID- 24323393
TI  - Antitumour necrosis factor alpha treatment reduces retinol-binding protein 4
      serum levels in non-diabetic ankylosing spondylitis patients.

PMID- 24323392
TI  - An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing
      granulomatosis with polyangiitis (Wegener's).
AB  - OBJECTIVES: To determine the safety and efficacy of abatacept in non-severe
      relapsing granulomatosis with polyangiitis (Wegener's)(GPA). METHODS: An open
      label trial of intravenous abatacept was conducted in 20 patients with non-severe
      relapsing GPA. Prednisone up to 30 mg daily was permitted within the first 2
      months, and patients on methotrexate, azathioprine, or mycophenolate mofetil
      continued these agents. Patients remained on study until common closing or early
      termination. RESULTS: Of the 20 patients, 18 (90%) had disease improvement, 16
      (80%) achieved remission (BVAS/WG=0) at a median of 1.9 months, and 14 (70%)
      reached common closing. Six patients (30%) met criteria for early termination due
      to increased disease activity; 3 of 6 achieved remission and relapsed at a median
      of 8.6 months. The median duration of remission before common closing was 14.4
      months, with the median duration of time on study for all patients being 12.3
      months (range 2-35 months). Eleven of the 15 (73%) patients on prednisone reached
      0 mg. Nine severe adverse events occurred in 7 patients, including 7 infections
      that were successfully treated. CONCLUSIONS: In this study of patients with non
      severe relapsing GPA, abatacept was well tolerated and was associated with a high
      frequency of disease remission and prednisone discontinuation.

PMID- 24323395
TI  - Costs for hospital care, drugs and lost work days in incident and prevalent
      rheumatoid arthritis: how large, and how are they distributed?
AB  - OBJECTIVE: To estimate the costs related to hospital care, drug use and work loss
      in prevalent and incident patients with rheumatoid arthritis (RA), and to
      describe their distribution. METHODS: A cohort of prevalent patients with RA >=18
      years on Jan 1, 2010, was identified from the Swedish National Patient Register
      (requiring >=2 visits listing RA) and the Swedish Rheumatology Quality Register,
      and followed until 31 December 2010. From the same registers, patients with the
      1st visit listing RA in 2009, with a 2nd visit within 1 year, were identified to
      the incident cohort, and were followed for 1 year. Five sex-matched, age-matched,
      education-matched and county-matched general population comparators were sampled
      per patient with RA. Costs were retrieved from national registers. RESULTS: The
      mean annual cost, including productivity losses per patients with RA (n=49 829)
      aged 18-64 years was ?23 147 versus ?8364 (median ?15 059 vs ?277) per
      comparator. In patients with RA >=65 years, the mean healthcare cost was ?6438
      versus ?2773 (median ?2458 vs ?677) per comparator. 13% of the patients accounted
      for 50% of the cost. For the incident patients with RA (n=2695), the mean monthly
      cost increased from a level close to the comparators 1 year before register
      identification (18-64 years: ?736 vs ?644; >=65 years: ?192 vs ?178), peaked the
      month following the identification date, and decreased to twice the cost of the
      comparators 1 year after diagnosis (18-64 years: ?1252 vs ?628; >=65 years: ?487
      vs ?230). CONCLUSIONS: The mean annual cost in patients with established RA, and
      mean monthly cost in newly diagnosed patients with RA, were 2-3 times higher than
      in the general population.

PMID- 24323396
TI  - Targeting Th2-typified immune responses to prevent immunopathology in rheumatic
      diseases: belittled therapeutic strategies?

PMID- 24323394
TI  - Testing the role of vitamin D in response to antitumour necrosis factor alpha
      therapy in a UK cohort: a Mendelian randomisation approach.

PMID- 24323398
TI  - Normoxic or hypoxic CD44/CD41 a2 B1 integrin-positive prostate PC3 cell side
      fractions and cancer stem cells.
AB  - A CD44/a 2 B 1- (CD41 integrin) and B-catenin-labeled fraction of PC3 prostate
      cancer cells is able to reconstitute cells representative of the original tumor
      in immuno-deficient mice (Li et al. in Cancer Res 68:1820-1825, 2008). After 48 h
      of culture under nitrogen with a resulting medium pH of 7.8, sorted hypoxic PC3
      cells yielded a higher percentage and concentration/10(5) of cells in a doubly
      labeled (DL) CD44(+)/CD41(+) side fraction compared with control cells cultured
      under normoxia (5 % CO2 in the ambient atmosphere at 37  degrees C). When the
      rise in pH was prevented (95 % N2, 5 % CO2), the difference in sorted hypoxic
      cell numbers remained. Sorted N and H DL cells and CD44(+)/CD41(-) cells were
      cultured under standard conditions. After 1-2 weeks, the number of attached
      colonies from formerly hypoxic cells, whether previously cultured with N2 or 95 %
      N2 + 5 % CO2, exceeded the number of doubly labeled normoxic cells, consistent
      with their greater initial concentration. Cultured sorted N or H CD44(+)/CD41(-)
      cells resulted in monolayers containing a small percentage of DL cells. Recovery
      of greater percentage and numbers of putative cancer stem cells, confirmed by
      quantitative cell sorting after culture under hypoxic conditions, is consistent
      with their greater relative numbers present in hypoxic niches. In addition, the
      report that neither CD44(+) nor CD41(+) epitopes were preferentially associated
      with FAM65B(high)/MF12(low)/LEF1(low) PC3 cells able to reconstitute tumors in
      immuno-deficient mice (Zhang and Waxman in Mol Cancer 9:319-330, 2010) suggests
      an in vitro mimic of tumor cell heterogeneity observed in epithelial cancers.

PMID- 24323397
TI  - Estrogen alleviates acetic acid-induced gastric or colonic damage via both
      ERalpha- and ERbeta-mediated and direct antioxidant mechanisms in rats.
AB  - In order to demonstrate the possible protective effects of estrogen receptor (ER)
      alpha and ERbeta receptor subtypes in the pathogenesis of colonic and gastric
      oxidant damage, experimental ulcer and colitis were induced by acetic acid, and
      the animals were randomly divided as colitis, ulcer, and their corresponding non
      ulcer and non-colitis control groups. Each group of rats was treated
      intramuscularly with the vehicle, selective ERalpha agonist propylpyrazole-triol
      (1 mg/kg), ERbeta agonist diarylpropionitrile (1 mg/kg), non-selective ER agonist
      17beta estradiol (E2; 1 mg/kg), or E2 plus non-selective ER antagonist ICI-182780
      (1 mg/kg). The results revealed that induction of ulcer or colitis resulted in
      systemic inflammation as assessed by increased levels of plasma TNF-alpha and IL
      6 levels. In both tissues, the presence of oxidant damage was verified by
      histological analysis and elevated myleoperoxidase activity. In the colitis and
      ulcer groups, both ER agonists and the non-selective E2 reversed the oxidative
      damage in a similar manner. These findings indicate that estrogen acts via both
      ERalpha- and ERbeta-mediated and direct antioxidant mechanisms, where both ER
      subtypes play equal and efficient roles in the anti-inflammatory action of
      estrogen, in limiting the migration of neutrophils to the inflamed tissue,
      reducing the release and activation of cytokines and thereby alleviating tissue
      damage. 

PMID- 24323399
TI  - HE4 combined with CA125: favorable screening tool for ovarian cancer.
AB  - Ovarian cancer is one of the most prevalent malignancies in women. Screening of
      the disease is done using variety of biomarkers. Diagnostic performance of
      current biomarkers of the disease such as human epididymis protein (HE4) and
      CA125 shows contradiction in previous studies. The goal of this study was to
      evaluate serum levels of CA125 and HE4 in Iranian patients with ovarian cancer
      and compare specificity and sensitivity of HE4, CA125 and HE4 + CA125 in patients
      with different stages and diverse histology. To evaluate CA125 and HE4, 32
      patients and 34 healthy women were selected. Origin of ovarian cancer was
      verified by expert gynecological oncologist. Significance and diagnostic
      performance were determined by ANOVA and receiver operator characteristic (ROC)
      and areas under the curve (AUC), respectively. Serum levels of CA125 and HE4 were
      significantly increased in patients in comparison with control group, especially
      for tumor cells originated from epithelium (p < 0.001). ROC-AUC for HE4, CA125
      and HE4 + CA125 were 0.91, 0.86 and 0.91, respectively. Specificity of HE4 was
      more than CA125 (85 vs. 80 %). Conversely, sensitivity of CA125 was higher in
      comparison with HE4 (90 vs. 80 %). It is being noticed that cutoff point of HE4
      and CA125 was 150 pmol/L and 38 U/mL, respectively. HE4 is slightly more specific
      for diagnosis of early stages of the disease, but the difference is not
      remarkable. CA125 and HE4 + CA125 have some diagnostic performance for prediction
      of advanced stages. Generally, the data of present study suggest that combining
      of HE4 and CA125 is a better screening tool for diagnosis of ovarian cancer.

PMID- 24323400
TI  - A low-cost tracked C-arm (TC-arm) upgrade system for versatile quantitative
      intraoperative imaging.
AB  - PURPOSE: C-arm fluoroscopy is frequently used in clinical applications as a low
      cost and mobile real-time qualitative assessment tool. C-arms, however, are not
      widely accepted for applications involving quantitative assessments, mainly due
      to the lack of reliable and low-cost position tracking methods, as well as
      adequate calibration and registration techniques. The solution suggested in this
      work is a tracked C-arm (TC-arm) which employs a low-cost sensor tracking module
      that can be retrofitted to any conventional C-arm for tracking the individual
      joints of the device. METHODS: Registration and offline calibration methods were
      developed that allow accurate tracking of the gantry and determination of the
      exact intrinsic and extrinsic parameters of the imaging system for any acquired
      fluoroscopic image. The performance of the system was evaluated in comparison to
      an Optotrak[Formula: see text] motion tracking system and by a series of
      experiments on accurately built ball-bearing phantoms. Accuracies of the system
      were determined for 2D-3D registration, three-dimensional landmark localization,
      and for generating panoramic stitched views in simulated intraoperative
      applications. RESULTS: The system was able to track the center point of the
      gantry with an accuracy of [Formula: see text] mm or better. Accuracies of 2D-3D
      registrations were [Formula: see text] mm and [Formula: see text]. Three
      dimensional landmark localization had an accuracy of [Formula: see text] of the
      length (or [Formula: see text] mm) on average, depending on whether the landmarks
      were located along, above, or across the table. The overall accuracies of the two
      dimensional measurements conducted on stitched panoramic images of the femur and
      lumbar spine were 2.5 [Formula: see text] 2.0 % [Formula: see text] and [Formula:
      see text], respectively. CONCLUSION: The TC-arm system has the potential to
      achieve sophisticated quantitative fluoroscopy assessment capabilities using an
      existing C-arm imaging system. This technology may be useful to improve the
      quality of orthopedic surgery and interventional radiology.

PMID- 24323401
TI  - Simulation of spatiotemporal CT data sets using a 4D MRI-based lung motion model.
AB  - PURPOSE: Four-dimensional CT imaging is widely used to account for motion-related
      effects during radiotherapy planning of lung cancer patients. However, 4D CT
      often contains motion artifacts, cannot be used to measure motion variability,
      and leads to higher dose exposure. In this article, we propose using 4D MRI to
      acquire motion information for the radiotherapy planning process. From the 4D MRI
      images, we derive a time-continuous model of the average patient-specific
      respiratory motion, which is then applied to simulate 4D CT data based on a
      static 3D CT. METHODS: The idea of the motion model is to represent the average
      lung motion over a respiratory cycle by cyclic B-spline curves. The model
      generation consists of motion field estimation in the 4D MRI data by nonlinear
      registration, assigning respiratory phases to the motion fields, and applying a B
      spline approximation on a voxel-by-voxel basis to describe the average voxel
      motion over a breathing cycle. To simulate a patient-specific 4D CT based on a
      static CT of the patient, a multi-modal registration strategy is introduced to
      transfer the motion model from MRI to the static CT coordinates. RESULTS:
      Differences between model-based estimated and measured motion vectors are on
      average 1.39 mm for amplitude-based binning of the 4D MRI data of three patients.
      In addition, the MRI-to-CT registration strategy is shown to be suitable for the
      model transformation. CONCLUSIONS: The application of our 4D MRI-based motion
      model for simulating 4D CT images provides advantages over standard 4D CT (less
      motion artifacts, radiation-free). This makes it interesting for radiotherapy
      planning.

PMID- 24323402
TI  - A laboratory comparison of computer navigation and individualized guides for
      distal radius osteotomy.
AB  - PURPOSE: This article presents the results of a multiuser, randomized laboratory
      trial comparing the accuracy and precision of image-based navigation against
      individualized guides for distal radius osteotomy (DRO). METHODS: Six surgeons
      each performed four DROs using image-based navigation and four DROs using
      individualized guides in a laboratory setting with plastic phantom replicas of
      radii from patients who had received DRO as treatment for radial deformity. Time
      required and correction errors of ulnar variance, radial inclination, and volar
      tilt were measured. RESULTS: There were no statistically significant differences
      in the average correction errors. There was a statistically significant
      difference in the standard deviation of ulnar variance error (2.0 mm for
      navigation vs. 0.6 mm for guides). There was a statistically significant
      difference in the standard deviation of radial inclination error ([Formula: see
      text] for navigation vs. [Formula: see text] for guides). There were
      statistically significant differences in the times required (705 s for navigation
      vs. 214 s for guides) and their standard deviations (144 s for navigation vs. 98
      s for guides). CONCLUSIONS: Compared to navigated DRO, individualized guides were
      easier to use, faster, and produced more precise correction of ulnar variance and
      radial inclination. The combination of true three-dimensional planning, ease of
      use, and accurate and precise corrective guidance makes the individualized guide
      technique a promising approach for performing corrective osteotomy of the distal
      radius.

PMID- 24323403
TI  - Salidroside induces rat mesenchymal stem cells to differentiate into dopaminergic
      neurons.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterised by the
      loss of substantia nigra dopaminergic neurons that leads to a reduction in
      striatal dopamine (DA) levels. Replacing lost cells by transplanting dopaminergic
      neurons has potential value to repair the damaged brain. Salidroside (SD), a
      phenylpropanoid glycoside isolated from plant Rhodiola rosea, is neuroprotective.
      We examined whether salidroside can induce mesenchymal stem cells (MSCs) to
      differentiate into neuron-like cells, and convert MSCs into dopamine neurons that
      can be applied in clinical use. Salidroside induced rMSCs to adopt a neuronal
      morphology, upregulated the expression of neuronal marker molecules, such as
      gamma neuronal enolase 2 (Eno2/NSE), microtubule-associated protein 2 (Map2), and
      beta 3 class III tubulin (Tubb3/beta-tubulin III). It also increased expression
      of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve
      growth factor (NGF) mRNAs, and promoted the secretion of these growth factors.
      The expression of dopamine neurons markers, such as dopamine-beta-hydroxy (DBH),
      dopa decarboxylase (DDC) and tyrosine hydroxylase (TH), was significantly
      upregulated after treatment with salidroside for 1-12 days. DA steadily increased
      after treatment with salidroside for 1-6 days. Thus salidroside can induce rMSCs
      to differentiate into dopaminergic neurons. 

PMID- 24323404
TI  - The SYNTAX score does not predict presence of carotid disease in a multivessel
      coronary disease population.
AB  - BACKGROUND: Numerous reports have shown the relationship between carotid artery
      atherosclerosis and coronary artery disease (CAD). However, the association
      between complex CAD evaluated by SYNTAX score (SxScore) and prevalence of carotid
      lesion (CL) has not been fully investigated. We sought to assess the prevalence
      of carotid atherosclerosis in patients with multivessel CAD assessed by SxScore
      and the relationship between SxScore severity and features of carotid
      atherosclerosis. METHODS AND RESULTS: Subjects were 204 consecutive patients with
      multivessel CAD assessed by coronary angiography and no previous history of
      carotid atherosclerosis that underwent carotid ultrasound scan from June 2012 to
      2013. Presence of CL, significant carotid disease (SCD) and carotid plaque
      morphology was evaluated. At least one CL was found in 159 patients (77.9%) with
      no significant difference among SxScore groups (P = 0.20 and P = 0.54,
      respectively). High prevalence of complex carotid plaque (CCP) was found without
      significant different distribution in SxScore groups (P = 0.69). Age was
      independently associated with the presence of CL [odds ratio (OR) 1.055; 95%
      confidence interval (CI): 1.015-1.097; P = 0.007] and SCD (OR 1.057; 95% CI:
      1.008-1.097; P = 0.019). Age and diabetes were independently associated with CCP
      (OR 1.58; 95% CI: 1.023-1.095; P = 0.001; OR 1.848; 95% CI: 1.026-3.327; P =
      0.041). SxScore was not independently associated with CL, SCD and CCP (all P >
      0.2). CONCLUSIONS: We found high prevalence of CL in patients with multivessel
      complex CAD. However, SxScore does not seem to correlate with carotid
      atherosclerosis.

PMID- 24323405
TI  - Comparison of sirolimus-eluting, paclitaxel-eluting, and bare-metal stents in a
      patient with angina pectoris: histopathological autopsy findings of the third
      month.
AB  - A 67-year-old man with a more than 15-year-old history of hypertension,
      dyslipidemia, and glucose intolerance presented at our hospital with exertional
      angina. Coronary angiography showed considerable stenosis of 3 vessels. A diffuse
      calcified lesion in the left anterior descending coronary artery was pre-treated
      using rotational atherectomy followed by sirolimus-eluting stent (SES)
      implantation. A lesion in the proximal right coronary artery was treated by bare
      metal stent (BMS) implantation, and the tandem lesion in the left circumflex
      artery was treated using paclitaxel-eluting stent (PES) implantation. All the
      procedures were performed within 1 month of the initial presentation and yielded
      good angiographic results. 3 months after the final stenting, the patient was re
      admitted because of congestive heart failure (CHF). While recovering from CHF, he
      suddenly developed cardiopulmonary arrest and died during hospitalization.
      Autopsy examination of the coronary arteries showed that both drug-eluting stents
      (DESs: SES and PES) and the BMS had characteristic histopathological features.
      Inflammatory responses in the neointima were greater in both the DESs than in the
      BMS. SES and PES showed different inflammatory infiltration pattern or fibrin
      deposition status; these histopathological differences observed in the DES
      environments have implication to cause adverse clinical events such as late stent
      thrombosis or late catch-up phenomena.

PMID- 24323406
TI  - Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas
      spp.).
AB  - Abnormal behavior, ranging from motor stereotypies to self-injurious behavior,
      has been documented in captive nonhuman primates, with risk factors including
      nursery rearing, single housing, and veterinary procedures. Much of this research
      has focused on macaque monkeys; less is known about the extent of and risk
      factors for abnormal behavior in baboons. Because abnormal behavior can be
      indicative of poor welfare, either past or present, the purpose of this study was
      to survey the presence of abnormal behavior in captive baboons and to identify
      potential risk factors for these behaviors with an aim of prevention. Subjects
      were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years
      temporarily singly housed for research or clinical reasons. A 15-min focal
      observation was conducted on each subject using the Noldus Observer(r) program.
      Abnormal behavior was observed in 26% of the subjects, with motor stereotypy
      (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively
      associated with age when first singly housed (P < 0.005) while self-directed
      behavior (e.g., hair pull, self-bite) was positively associated with the lifetime
      number of days singly housed (P < 0.05) and the average number of blood draws per
      year (P < 0.05). In addition, abnormal appetitive behavior was associated with
      being male (P < 0.05). Although the baboons in this study exhibited relatively
      low levels of abnormal behavior, the risk factors for these behaviors (e.g.,
      social restriction, routine veterinary procedures, and sex) appear to remain
      consistent across primate species.

PMID- 24323407
TI  - Detection of submicroscopic chromosomal aberrations by array-based comparative
      genomic hybridization in fetuses with congenital heart disease.
AB  - OBJECTIVES: To evaluate the usefulness of array-based comparative genomic
      hybridization (aCGH) for prenatal genetic diagnosis of congenital heart disease
      (CHD), with and without associated anomalies, and to explore the relationship
      between submicroscopic chromosomal aberrations and CHD. METHODS: In this
      prospective study we investigated 76 consecutive singleton fetuses with abnormal
      cardiac ultrasound findings, normal karyotype and negative or no fluorescence in
      situ hybridization results for 22q11.2 deletion syndrome. All pregnancies
      underwent aCGH in a comprehensive search for chromosomal aberrations. The
      relationship between copy number variations (CNVs) and CHD was determined by
      comparing clinical findings to chromosomal databases. RESULTS: CNVs that were
      benign or had no clinical significance were detected in 18/76 (23.7%) cases. CNVs
      of unknown clinical significance (i.e. VOUS) were detected in 4/76 (5.3%) cases.
      Pathogenic CNVs were detected in 5/76 (6.6%) cases. Fetuses with CHD and
      additional structural abnormalities demonstrated no difference in number of
      pathogenic CNVs when compared with fetuses with isolated CHD (7.4% (n = 2/27) vs
      6.1% (n = 3/49), P > 0.05). CONCLUSION: In this study cohort, aCGH analysis
      significantly improved the detection of submicroscopic chromosomal aberrations in
      pregnancies with CHD, as compared with conventional cytogenetics. Our results
      suggest that aCGH can provide additional genetic information in fetuses with
      abnormal heart findings.

PMID- 24323408
TI  - Evaluation of hydroxyatrazine in the endocrine disruptor screening and testing
      program's male and female pubertal protocols.
AB  - Two critical components of the validation of any in vivo screening assay are to
      demonstrate sensitivity and specificity. Although the Endocrine Disruptor
      Screening Program's Tier 1 Male and Female Pubertal Protocols have been shown to
      be sensitive assays for the detection of weak endocrine disrupting chemicals
      (EDCs), there are concerns that the assays lack specificity for EDC effects when
      a chemical induces systemic toxicity. A lack of specificity, or the ability to
      correctly identify an inactive or "negative" chemical, would increase the
      probability of identifying false positives. Here, we orally exposed rats to
      hydroxyatrazine (OH-ATR), a biotransformation by-product of the chlorotriazine
      herbicides that produced nephrotoxicity following a 13-week dietary exposure.
      Based on a previous study in our laboratory, males were dosed with 11.4 to 183.4
      mg/kg OH-ATR and females were dosed with 45.75 to 183.4 mg/kg OH-ATR. Following
      exposure in both sexes, there was a dose-response increase in mean kidney weights
      and the incidence and severity of kidney lesions. These lesions included the
      deposition of mineralized renal tubule concretions, hydronephrosis, renal tubule
      dilatation, and pyelonephritis. However, no differences in body weight, liver
      weight, or reproductive tissue weights, reproductive or thyroid histology,
      hormone concentrations or the age of pubertal onset were observed. Therefore, the
      results demonstrate that the endpoints included in the pubertal assay are useful
      for nonendocrine (systemic) effects that define an no observable effect level
      (NOEL) or lowest observable effect level (LOEL) and provide one example where an
      impact on kidney function does not alter any of the endocrine-specific endpoints
      of the assay. 

PMID- 24323410
TI  - Neonatal exposure to estradiol valerate increases dopamine content in
      nigrostriatal pathway during adulthood in the rat.
AB  - Research in programming has focused in the study of stimuli that affect sensitive
      periods of development such as prenatal and neonatal stage. We previously showed
      that exposure to estradiol valerate to female rats during the first 12 h of life
      increased catecholamine content in ventromedial-arcuatus hypothalamus of the
      adult rat. However, changes in others dopaminergic circuits have not been
      studied. The purpose of this work was to determine the neurotransmitters changes
      induced by neonatal estradiol valerate (0.1 mg/50 MUl s. c. per rat)
      administration on nigrostriatal pathway of adult female rats. Sesame oil (50 MUl
      s. c. per rat) was administered in a control parallel group. EV-1 adult rats
      presented effective markers of long-term estrogenization as decreased serum
      levels of progesterone and a reduction in the size of estrogen-sensitive organs.
      In the brain, neonatal estradiol valerate administration led to a significant
      increase in dopamine content in striatum, substantia nigra and ventral tegmental
      area. With respect to the contents of dopamine metabolites, only 3
      methoxytyramine content increased in substantia nigra and ventral tegmental area.
      In addition, the content of noradrenaline increased only in striatum.
      Interestingly, estrogenized rats lacked locomotor activity induced by acute dose
      of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal
      exposure to estradiol valerate permanently modified the content of monoamine
      neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor
      activity of adult female rats. This might imply that estrogenized rats could have
      changes in the expression of key proteins in dopaminergic regulation, as tyrosine
      hydroxylase and dopamine transporter.

PMID- 24323411
TI  - Compression stockings for the initial treatment of varicose veins in patients
      without venous ulceration.
AB  - BACKGROUND: Compression hosiery or stockings are often the first line of
      treatment for varicose veins in people without either healed or active venous
      ulceration. Evidence is required to determine whether the use of compression
      stockings can effectively manage and treat varicose veins in the early stages.
      This is an update of a review first published in 2011. OBJECTIVES: To assess the
      effectiveness of compression stockings for the only and initial treatment of
      varicose veins in patients without healed or active venous ulceration. SEARCH
      METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials
      Search Co-ordinator searched the Specialised Register (last searched August 2013)
      and CENTRAL (2013, Issue 5). SELECTION CRITERIA: Randomised controlled trials
      (RCTs) were included if they involved participants diagnosed with primary trunk
      varicose veins without healed or active venous ulceration (Clinical, Etiology,
      Anatomy, Pathophysiology (CEAP) classification C2 to C4). Included trials
      assessed compression stockings versus no treatment, compression versus placebo
      stockings, or compression stockings plus drug intervention versus drug
      intervention alone. Trials comparing different lengths and pressures of stockings
      were also included. Trials involving other types of treatment for varicose veins
      (either as a comparator to stockings or as an initial non-randomised treatment),
      including sclerotherapy and surgery, were excluded. DATA COLLECTION AND ANALYSIS:
      Two authors assessed the trials for inclusion and quality (SS and LR). SS
      extracted the data, which were checked by LR. Attempts were made to contact trial
      authors where missing or unclear data were present. MAIN RESULTS: Seven studies
      involving 356 participants with varicose veins without healed or active venous
      ulceration were included. Different levels of pressure were exerted by the
      stockings in the studies, ranging from 10 to 50 mmHg. One study assessed
      compression hosiery versus no compression hosiery. The other six compared
      different types or pressures of stockings. The methodological quality of all
      included trials was unclear, mainly because of inadequate reporting.The symptoms
      subjectively improved with the wearing of stockings across trials that assessed
      this outcome, but these assessments were not made by comparing one randomised arm
      of a trial with a control arm and are therefore subject to bias.Meta-analyses
      were not undertaken due to inadequate reporting and actual or suspected high
      levels of heterogeneity. AUTHORS' CONCLUSIONS: There is insufficient, high
      quality evidence to determine whether or not compression stockings are effective
      as the sole and initial treatment of varicose veins in people without healed or
      active venous ulceration, or whether any type of stocking is superior to any
      other type. Future research should consist of a large RCT of participants with
      trunk varices either wearing or not wearing compression stockings to assess the
      efficacy of this intervention. If compression stockings are found to be
      beneficial, further studies assessing which length and pressure is the most
      efficacious could then take place.

PMID- 24323412
TI  - Protein misfolding and organelle stress after brain ischemia.

PMID- 24323413
TI  - Protein misfolding, aggregation, and autophagy after brain ischemia.
AB  - Ischemic brain injury is a common disorder linked to a variety of diseases.
      Significant progress has been made in our understanding of the underlying
      mechanisms. Previous studies show that protein misfolding, aggregation, and
      multiple organelle damage are major pathological events in postischemic neurons.
      The autophagy pathway is the chief route for bulk degradation of protein
      aggregates and damaged organelles. The latest studies suggest that impairment of
      autophagy contributes to abnormal protein aggregation and organelle damages after
      brain ischemia. This article reviews recent studies of protein misfolding,
      aggregation, and impairment of autophagy after brain ischemia. 

PMID- 24323414
TI  - HuR function and translational state analysis following global brain ischemia and
      reperfusion.
AB  - Prolonged translation arrest in post-ischemic hippocampal CA1 pyramidal neurons
      precludes translation of induced stress genes and directly correlates with cell
      death. We evaluated the regulation of mRNAs containing adenine- and uridine-rich
      elements (ARE) by assessing HuR protein and hsp70 mRNA nuclear translocation, HuR
      polysome binding, and translation state analysis of CA1 and CA3 at 8 h of
      reperfusion after 10 min of global cerebral ischemia. There was no difference
      between CA1 and CA3 at 8 h of reperfusion in nuclear or cytoplasmic HuR protein
      or hsp70 mRNA, or HuR polysome association, suggesting that neither mechanism
      contributed to post-ischemic outcome. Translation state analysis revealed that 28
      and 58 % of unique mRNAs significantly different between 8hR and NIC, in CA3 and
      CA1, respectively, were not polysome-bound. There was significantly greater
      diversity of polysome-bound mRNAs in reperfused CA3 compared to CA1, and in both
      regions, ARE-containing mRNAs accounted for 4-5 % of the total. These data
      indicate that posttranscriptional ARE-containing mRNA regulation occurs in
      reperfused neurons and contributes to post-ischemic outcome. Understanding the
      differential responses of vulnerable and resistant neurons to ischemia will
      contribute to the development of effective neuroprotective therapies.

PMID- 24323415
TI  - mRNA redistribution during permanent focal cerebral ischemia.
AB  - Translation arrest occurs in neurons following focal cerebral ischemia and is
      irreversible in penumbral neurons destined to die. Following global cerebral
      ischemia, mRNA is sequestered away from 40S ribosomal subunits as mRNA granules,
      precluding translation. Here, we investigated mRNA granule formation using
      fluorescence in situ histochemistry out to 8 h permanent focal cerebral ischemia
      using middle cerebral artery occlusion in Long Evans rats with and without
      diabetes. Neuronal mRNA granules colocalized with PABP, HuR, and NeuN, but not
      40S or 60S ribosomal subunits, or organelle markers. The volume of brain with
      mRNA granule-containing neurons decreased exponentially with ischemia duration,
      and was zero after 8 h permanent focal cerebral ischemia or any duration of
      ischemia in diabetic rats. These results show that neuronal mRNA granule response
      has a limited range of insult intensity over which it is expressed. Identifying
      the limits of effective neuronal stress response to ischemia will be important
      for developing effective stroke therapies.

PMID- 24323417
TI  - ER stress and effects of DHA as an ER stress inhibitor.
AB  - The endoplasmic reticulum (ER) functions in the synthesis, folding, modification,
      and transport of newly synthesized transmembrane and secretory proteins. The ER
      also has important roles in the storage of intracellular Ca(2+) and regulation of
      Ca(2+) homeostasis. The integrity of the Ca(2+) homeostasis in the ER lumen is
      vital for proper folding of proteins. Dysregulation of ER Ca(2+) could result in
      an increase in unfolded or misfolded proteins and ER stress. ER stress triggers
      activation of the unfolded protein response (UPR), which is a fundamentally
      adaptive cell response and functions as a cytoprotective mechanism by over
      expression of relevant chaperones and the global shutdown of protein synthesis.
      UPR activation occurs when three key ER membrane-sensor proteins detect an
      accumulation of aberrant proteins. The UPR acts to alleviate ER stress, but if
      the stress is too severe or prolonged, apoptosis will be triggered. In this
      review, we focused on ER stress and the effects of docosahexaenoic acid (DHA) on
      ER stress. DHA and its bioactive compounds, such as protectins and resolvins,
      provide neuroprotection against oxidative stress and apoptosis and have the
      ability to resolve inflammation in neurological diseases. New studies reveal that
      DHA blocks inositol trisphosphate receptor (IP3R)-mediated ER Ca(2+) depletion
      and ER stress. The administration of DHA post-traumatic brain injury (TBI)
      reduces ER stress, aberrant protein accumulation, and neurological deficits.
      Therefore, DHA presents therapeutic potentials for TBI via its pleiotropic
      effects including inhibition of ER stress. 

PMID- 24323418
TI  - Augmentation of normal and glutamate-impaired neuronal respiratory capacity by
      exogenous alternative biofuels.
AB  - Mitochondrial respiratory capacity is critical for responding to changes in
      neuronal energy demand. One approach toward neuroprotection is the administration
      of alternative energy substrates ("biofuels") to overcome brain injury-induced
      inhibition of glucose-based aerobic energy metabolism. This study tested the
      hypothesis that exogenous pyruvate, lactate, beta-hydroxybutyrate, and acetyl-L
      carnitine each increase neuronal respiratory capacity in vitro either in the
      absence of or following transient excitotoxic glutamate receptor stimulation.
      Compared to the presence of 5 mM glucose alone, the addition of pyruvate,
      lactate, or beta-hydroxybutyrate (1.0-10.0 mM) to either day in vitro (DIV) 14 or
      7 rat cortical neurons resulted in significant, dose-dependent stimulation of
      respiratory capacity, measured by cell respirometry as the maximal O2 consumption
      rate in the presence of the respiratory uncoupler carbonyl cyanide-p
      trifluoromethoxyphenylhydrazone. A 30-min exposure to 100 MUM glutamate impaired
      respiratory capacity for DIV 14, but not DIV 7, neurons. Glutamate reduced the
      respiratory capacity for DIV 14 neurons with glucose alone by 25 % and also
      reduced respiratory capacity with glucose plus pyruvate, lactate, or beta
      hydroxybutyrate. However, respiratory capacity in glutamate-exposed neurons
      following pyruvate or beta-hydroxybutyrate addition was still, at least, as high
      as that obtained with glucose alone in the absence of glutamate exposure. These
      results support the interpretation that previously observed neuroprotection by
      exogenous pyruvate, lactate, or beta-hydroxybutyrate is at least partially
      mediated by their preservation of neuronal respiratory capacity.

PMID- 24323416
TI  - Mitochondrial dysfunction and NAD(+) metabolism alterations in the
      pathophysiology of acute brain injury.
AB  - Mitochondrial dysfunction is commonly believed to be one of the major players in
      mechanisms of brain injury. For several decades, pathologic mitochondrial calcium
      overload and associated opening of the mitochondrial permeability transition
      (MPT) pore were considered a detrimental factor causing mitochondrial damage and
      bioenergetics failure. Mitochondrial and cellular bioenergetic metabolism depends
      on the enzymatic reactions that require NAD(+) or its reduced form NADH as
      cofactors. Recently, it was shown that NAD(+) also has an important function as a
      substrate for several NAD(+) glycohydrolases whose overactivation can contribute
      to cell death mechanisms. Furthermore, downstream metabolites of NAD(+)
      catabolism can also adversely affect cell viability. In contrast to the negative
      effects of NAD(+)-catabolizing enzymes, enzymes that constitute the NAD(+)
      biosynthesis pathway possess neuroprotective properties. In the first part of
      this review, we discuss the role of MPT in acute brain injury and its role in
      mitochondrial NAD(+) metabolism. Next, we focus on individual NAD(+)
      glycohydrolases, both cytosolic and mitochondrial, and their role in NAD(+)
      catabolism and brain damage. Finally, we discuss the potential effects of
      downstream products of NAD(+) degradation and associated enzymes as well as the
      role of NAD(+) resynthesis enzymes as potential therapeutic targets. 

PMID- 24323419
TI  - Fission and fusion of the neuronal endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) is central for protein synthesis and is the
      largest intracellular Ca2+ store in neurons. The neuronal ER is classically
      described to have a continuous lumen spanning all cellular compartments. This
      allows neuronal ER to integrate spatially separate events in the cell. Recent in
      vitro as well as in vivo findings, however, demonstrate that the neuronal ER is a
      structurally dynamic entity, capable of rapid fragmentation, i.e., ER fission.
      The ER fragments can fuse back together and reinstate ER continuity. This
      reversible phenomenon can be induced repeatedly within the same cell, is
      temperature-dependent, and compatible with cell survival. The key trigger for
      dendritic ER fission is N-methyl D-aspartate (NMDA) receptor stimulation in the
      presence of extracellular Ca2+. However, the exact molecular machinery
      responsible for the fission and fusion of neuronal ER remains unknown. Reversible
      ER fission represents a new cell biological event downstream of NMDA receptor
      gated Ca2+ influx and may thus influence many aspects of neuronal function in
      physiology and disease. Hence, it constitutes a new field for exploration in
      neuroscience that will benefit greatly from recent advances in light microscopy
      imaging techniques allowing dynamic characterization of cellular events in vitro
      and in vivo. 

PMID- 24323420
TI  - SIRT1 regulation modulates stroke outcome.
AB  - Silent information regulator 1 (SIRT1) is a NAD+-dependent histone deacetylase
      that represses gene expression and plays a role in longevity. SIRT1 responds to
      diverse stress conditions and regulates metabolism in nutrient deficiency
      conditions; therefore, it is involved in adaptive pathways to better fulfill
      tissue needs in a disturbed environment. SIRT1 overexpression or activation is
      protective in neurodegenerative diseases. Its role in acute nervous system
      injury, such as brain ischemia, is emerging, but whether SIRT1 activation
      improves stroke outcome is still a matter of controversy. In the present review,
      we will document present knowledge about the contribution of SIRT1 in
      death/survival in cell and animal models of brain ischemia and discuss whether
      SIRT1 could be a valuable target for therapeutic intervention in human stroke. 

PMID- 24323421
TI  - Lysosomal membrane permeabilization as a key player in brain ischemic cell death:
      a "lysosomocentric" hypothesis for ischemic brain damage.
AB  - This is a speculative review of the role of the lysosome in ischemic cell death
      in the mammalian brain. In particular, it focuses on the role of the
      permeabilization of the lysosomal membrane to proteins (LMP) as a major mechanism
      of cell death in mild, but lethal, ischemic insults. The first section of the
      review outlines the evidence that this is the case, using the relatively few
      extant studies of mammalian brain. In the second section of the review, the
      mechanism by which an ischemic insult might lead to LMP is discussed. A metabolic
      sequence including NMDA receptor activation, activation of phospholipase A2 and
      production of free radicals, and also the activation of calpain are shown to be
      critical. The remainder of the section speculates on the actual agent(s) which
      may be causing the lysosomal membrane change, based on extensive literature
      references. There is currently no knowledge of the actual mechanism. The third
      section considers potential targets of the released lysosomal proteases and other
      proteins that might mediate the lethal effects of LMP, focusing largely on the
      mitochondria as the target. Again, this is speculative as the targets are not
      known. Finally, the fourth section addresses the level of importance that LMP has
      in the process of ischemic cell death and concludes that it may well play the
      major role during mild but lethal ischemic insults. This novel, so-called
      "lysosomocentric," hypothesis is briefly critiqued. The therapeutic potential of
      this conclusion is then discussed. 

PMID- 24323422
TI  - Heat shock proteins in the brain: role of Hsp70, Hsp 27, and HO-1 (Hsp32) and
      their therapeutic potential.
AB  - Heat shock proteins (Hsps) are induced by heat shock via heat shock factor
      proteins binding to heat shock elements in their promoters. Hsp70 is massively
      induced in response to misfolded proteins following cerebral ischemia in all cell
      types but is induced mainly in neurons in the ischemic penumbra. Overexpression
      of Hsp70 via transgenes and viruses or systemic administration of Hsp70 fusion
      proteins that allow it to cross the blood brain barrier protects the brain
      against ischemia in most reported studies. Hsp27 can exist as unphosphorylated
      large oligomers that prevent misfolded protein aggregates and improve cell
      survival. P-Hsp27 small oligomers bind specific protein targets to improve
      survival. In the brain, protein kinase D phosphorylates Hsp27 following ischemia
      which then binds apoptosis signal-regulating kinase 1 to prevent MKK4/7, c-Jun
      NH(2)-terminal kinase, and Jun-induced apoptosis, and decrease infarct volumes
      following focal cerebral ischemia. Heme oxygenase-1 (HO-1) metabolizes heme to
      carbon monoxide, ferrous ion, and biliverdin. CO activates cGMP to promote
      vasodilation, and biliverdin is converted to bilirubin which can serve as an anti
      oxidant, both of which may contribute to the reported protective role of HO-1 in
      cerebral ischemia and subarachnoid hemorrhage. However, ferrous ion can react
      with hydrogen peroxide to produce pro-oxidant hydroxyl radicals which may explain
      the harmful role of HO-1 in intracerebral hemorrhage. Heat shock proteins as a
      class have great potential as treatments for cerebrovascular disease and have yet
      to be tested in the clinic. 

PMID- 24323425
TI  - Pseudo-continuous arterial spin labelling MRI for non-invasive, whole-brain,
      serial quantification of cerebral blood flow following aneurysmal subarachnoid
      haemorrhage.
AB  - Delayed cerebral ischaemia (DCI) is the major cause of mortality and morbidity
      following aneurysmal subarachnoid haemorrhage (SAH). Recent experimental evidence
      from animal models has highlighted the need for non-invasive and robust
      measurements of brain tissue perfusion in patients in order to help understand
      the pathophysiology underlying DCI. Quantitative, serial, whole-brain cerebral
      perfusion measurements were obtained with pseudo-continuous arterial spin
      labelling (PCASL) magnetic resonance imaging (MRI) in six SAH patients acutely
      following endovascular coiling. This technique requires no injected contrast or
      radioactive isotopes. MRI scanning was well tolerated. Artefact from endovascular
      coils was minimal. PCASL MRI was able to detect time-dependent and patient
      specific changes in voxel-wise and regional cerebral blood flow. These changes
      reflected changes in clinical condition. Data obtained in healthy controls using
      the same experimental protocol confirm the reliability and reproducibility of
      these results. This is the first study to use whole-brain, quantitative PCASL to
      identify time-dependent changes in cerebral blood flow at the tissue level in the
      acute period following SAH. This technique has the potential to better understand
      changes in cerebral pathophysiology as a consequence of aneurysm rupture. 

PMID- 24323423
TI  - MicroRNAs regulate the chaperone network in cerebral ischemia.
AB  - The highly evolutionarily conserved 70 kDa heat shock protein (HSP70) family was
      first understood for its role in protein folding and response to stress.
      Subsequently, additional functions have been identified for it in regulation of
      organelle interaction, of the inflammatory response, and of cell death and
      survival. Overexpression of HSP70 family members is associated with increased
      resistance to and improved recovery from cerebral ischemia. MicroRNAs (miRNAs)
      are important posttranscriptional regulators that interact with multiple target
      messenger RNAs (mRNA) coordinately regulating target genes, including chaperones.
      The members of the HSP70 family are now appreciated to work together as networks
      to facilitate organelle communication and regulate inflammatory signaling and
      cell survival after cerebral ischemia. This review will focus on the new concept
      of the role of the chaperone network in the organelle network and its novel
      regulation by miRNA.

PMID- 24323424
TI  - Fast neuroprotection (fast-NPRX) for acute ischemic stroke victims: the time for
      treatment is now.

PMID- 24323426
TI  - Bipyridine, an iron chelator, does not lessen intracerebral iron-induced damage
      or improve outcome after intracerebral hemorrhagic stroke in rats.
AB  - Iron chelators, such as the intracellular ferrous chelator 2,2'-bipyridine, are a
      potential means of ameliorating iron-induced injury after intracerebral
      hemorrhage (ICH). We evaluated bipyridine against the collagenase and whole-blood
      ICH models and a simplified model of iron-induced damage involving a striatal
      injection of FeCl2 in adult rats. First, we assessed whether bipyridine (25 mg/kg
      beginning 12 h post-ICH and every 12 h for 3 days) would attenuate non-heme iron
      levels in the brain and lessen behavioral impairments (neurological deficit
      scale, corner turn test, and horizontal ladder) 7 days after collagenase-induced
      ICH. Second, we evaluated bipyridine (20 mg/kg beginning 6 h post-ICH and then
      every 24 h) on edema 3 days after collagenase infusion. Body temperature was
      continually recorded in a subset of these rats beginning 24 h prior to ICH until
      euthanasia. Third, bipyridine was administered (as per experiment 2) after whole
      blood infusion to examine tissue loss, neuronal degeneration, and behavioral
      impairments at 7 days post-stroke, as well as body temperature for 3 days post
      stroke. Finally, we evaluated whether bipyridine (25 mg/kg given 2 h prior to
      surgery and then every 12 h for 3 days) lessens tissue loss, neuronal death, and
      behavioral deficits after striatal FeCl2 injection. Bipyridine caused a
      significant hypothermic effect (maximum drop to 34.6  degrees C for 2-5 h after
      each injection) in both ICH models; however, in all experiments bipyridine
      treated rats were indistinguishable from vehicle controls on all other measures
      (e.g., tissue loss, behavioral impairments, etc.). These results do not support
      the use of bipyridine against ICH.

PMID- 24323428
TI  - Hyperphosphorylated tau is implicated in acquired epilepsy and neuropsychiatric
      comorbidities.
AB  - Epilepsy is a common group of neurological diseases. Acquired epilepsy can be
      caused by brain insults, such as trauma, infection or tumour, and followed by a
      latent period from several months to years before the emergence of recurrent
      spontaneous seizures. More than 50% of epilepsy cases will develop chronic
      neurodegenerative, neurocognitive and neuropsychiatric comorbidities. It is
      important to understand the mechanisms by which a brain insult results in
      acquired epilepsy and comorbidities in order to identify targets for novel
      therapeutic interventions that may mitigate these outcomes. Recent studies have
      implicated the hyperphosphorylated tubulin-associated protein (tau) in rodent
      models of epilepsy and Alzheimer's disease, and in experimental and clinical
      studies of traumatic brain injury. This potentially represents a novel target to
      mitigate epilepsy and associated neurocognitive and psychiatric disorders post
      brain injury. This article reviews the potential role of tau-based mechanisms in
      the pathophysiology of acquired epilepsy and its neurocognitive and
      neuropsychiatric comorbidities, and the potential to target these for novel
      disease-modifying treatments.

PMID- 24323429
TI  - MGARP regulates mouse neocortical development via mitochondrial positioning.
AB  - Neocortical development is an extremely complicated process that critically
      depends on the proper migration, distribution, and positioning of neural cells.
      Here, we identified mitochondria-localized glutamic acid-rich protein (MGARP) as
      a negative regulator of neocortical development. In the developing neocortex, the
      overexpression of MGARP by in utero electroporation impedes the radial migration
      of neocortical cells to their final destination. These neocortical cells failed
      to be normally polarized, leading to shortened axons and compromised axonal
      bundles. The number of dendrites was also attenuated in cells with MGARP
      overexpression and was expanded in MGARP-knockdown or knockout cells. Mechanistic
      studies indicated that overexpression of MGARP caused alterations in the
      structural integrity, subcellular distribution, and motility of mitochondria. The
      mitochondria in MGARP-overexpressing cells became "fatty" with a round
      morphology, and the total number of mitochondria in MGARP-overexpressing cells
      was also decreased in the cell body and dendrites as well as in the axons. Time
      lapse studies showed that the ratio of motile mitochondria was remarkably
      decreased in the axons of MGARP-overexpressing cells. Together, our findings
      suggest that MGARP negatively mediates neocortical development by regulating
      mitochondrial distribution and motility in neocortical neurons. 

PMID- 24323430
TI  - A pyrene derivative for Hg(2+) -selective fluorescent sensing and its application
      in in vivo imaging.
AB  - An Hg(2+) -selective fluorescent sensor (1) bearing pyrene as a fluorophore was
      synthesized. A sandwich-stacking binding mode was formed during the binding
      process, which increased the excimer fluorescence 22-fold at 490 nm. Compound 1
      was successfully applied in in vivo imaging to trace the enrichment and
      distribution of mercury in the nervous system, digestive system, and reproductive
      system of Caenorhabditis elegans, as well as the organs of zebrafish. 

PMID- 24323427
TI  - New insight into neurodegeneration: the role of proteomics.
AB  - Recent advances within the field of proteomics, including both upstream and
      downstream protocols, have fuelled a transition from simple protein
      identification to functional analysis. A battery of proteomics approaches is now
      being employed for the analysis of protein expression levels, the monitoring of
      cellular activities and for gaining an increased understanding into biochemical
      pathways. Combined, these approaches are changing the way we study disease by
      allowing accurate and targeted, large scale protein analysis, which will provide
      invaluable insight into disease pathogenesis. Neurodegenerative disorders,
      including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's
      disease (HD), amyotrophic lateral sclerosis (ALS), prion disease, and other
      diseases that affect the neuromuscular system, are a leading cause of disability
      in the aging population. There are no effective intervention strategies for these
      disorders and diagnosis is challenging as it relies primarily on clinical
      symptomatic features, which often overlap at early stages of disease. There is,
      therefore, an urgent need to develop reliable biomarkers to improve early and
      specific diagnosis, to track disease progression, to measure molecular responses
      towards treatment regimes and ultimately devise new therapeutic strategies. To
      accomplish this, a better understanding of disease mechanisms is needed. In this
      review we summarize recent advances in the field of proteomics applicable to
      neurodegenerative disorders, and how these advances are fueling our
      understanding, diagnosis, and treatment of these complex disorders. 

PMID- 24323431
TI  - Solid-phase microextraction based on polyaniline doped with
      perfluorooctanesulfonic acid coupled to HPLC for the quantitative determination
      of chlorophenols in water samples.
AB  - A porous and highly efficient polyaniline-based solid-phase microextraction
      (SPME) coating was successfully prepared by the electrochemical deposition
      method. A method based on headspace SPME followed by HPLC was established to
      rapidly determine trace chlorophenols in water samples. Influential parameters
      for the SPME, including extraction mode, extraction temperature and time, pH and
      ionic strength procedures, were investigated intensively. Under the optimized
      conditions, the proposed method was linear in the range of 0.5-200 MUg/L for 4
      chlorophenol and 2,4,6-trichlorophenol, 0.2-200 MUg/L for 2,4-dichlorophenol and
      2-200 MUg/L for 2,3,4,6-tetrachlorophenol and pentachlorophenol, with
      satisfactory correlation coefficients (>0.99). RSDs were <15% (n = 5) and LODs
      were relatively low (0.10-0.50 MUg/L). Compared to commercial 85 MUm polyacrylate
      and 60 MUm polydimethylsiloxane/divinylbenzene fibers, the homemade polyaniline
      fiber showed a higher extraction efficiency. The proposed method has been
      successfully applied to the determination of chlorophenols in water samples with
      satisfactory recoveries. 

PMID- 24323432
TI  - Trends and risk factors for transfusion in hepatopancreatobiliary surgery.
AB  - INTRODUCTION: Patient-specific factors impacting the need for possible
      perioperative blood transfusions have not been examined in patients undergoing
      hepatopancreatobiliary (HPB) procedures. We sought to define the overall
      utilization of blood transfusions for HPB surgery stratified by procedure type,
      as well as identify patient-level risk factors for transfusion. METHODS: Hepatic
      and pancreatic resections were selected from the 2005-2011 American College of
      Surgeons National Surgical Quality Improvement Program's public use files.
      Transfusion utilization, risk factors, temporal trends, and outcomes were
      assessed using regression models. Missing data were addressed using multiple
      imputation. RESULTS: Twenty-six thousand eight hundred twenty-seven patients met
      the inclusion criteria. There were 16,953 pancreas cases (distal pancreatectomy
      (31.2%), pancreaticoduodenectomy (65.8%), total pancreatectomy (3.0%)), and 9,874
      liver cases (wedge resection (60.0%), hemi-hepatectomy (30.1%), trisegmentectomy
      (9.9%)). Overall, 25.7% patients received a perioperative transfusion.
      Transfusion rates varied by operation type (hepatic wedge resection 18.7%,
      lobectomy 31.3%, trisegmentectomy 39.8%, distal pancreatectomy 19.8%, Whipple
      28.7%, total pancreatectomy 43.6%, p < 0.001). On multivariate analysis, several
      patient-level factors were strongly associated with the risk of transfusion:
      preoperative hematocrit <36% (risk ratios (RR) 1.99, 95% CI 1.91-2.08),
      preoperative albumin <3.0 g/dL (RR 1.25, 95% CI 1.19-1.31), American Society of
      Anesthesiologists (ASA) class IV (RR 1.24, 95% CI 1.16-1.33), and
      anticoagulation/bleeding disorder (RR 1.26, 95% CI 1.15-1.38) (all p < 0.001).
      Patients with any one of these high-risk factors had an over twofold increased
      risk of perioperative transfusion (RR 2.31, 95% CI 2.21-2.40, p < 0.001).
      CONCLUSION: There are large differences in the incidence of transfusion among
      patients undergoing HPB procedures. While the type of HPB procedure was
      associated with the risk of transfusion, patient-level factors-including
      preoperative hematocrit and albumin, ASA classification, and history of
      anticoagulation/bleeding disorder-were as important.

PMID- 24323433
TI  - A Lallzyme MMX-based rapid method for fission yeast protoplast preparation.
AB  - Fungal cells including yeasts are surrounded by cell wall that counteracts turgor
      pressure and prevents cell lysis. Many yeast experiments, including genetic
      manipulation of sterile strains, morphogenesis studies, nucleic acid isolation
      and many others, require mechanical breakage or enzymatic removal of the cell
      wall. Some of these experiments require the generation of live cells lacking cell
      walls, called protoplasts, that can be maintained in osmostabilized medium.
      Enzymatic digestion of cell wall proteoglycans is a commonly used method of
      protoplast preparation. Currently existing protocols for fission yeast cell wall
      digestion are time consuming and not very efficient. We developed a new rapid
      method for fission yeast protoplast preparation that relies on digesting cell
      walls with Lallzyme MMX commercial enzyme mix, which produces protoplasts from
      all cells in less than 10 min. We demonstrate that these protoplasts can be
      utilized in three commonly used fission yeast protocols. Thus, we provide the
      fission yeast community with a robust and efficient plasmid extraction method, a
      new protocol for diploid generation and an assay for protoplast recovery that
      should be useful for studies of morphogenesis. Our method is potentially
      applicable to other yeasts and fungi.

PMID- 24323434
TI  - A fucose containing polymer-rich fraction from the brown alga Ascophyllum nodosum
      mediates lifespan increase and thermal-tolerance in Caenorhabditis elegans, by
      differential effects on gene and protein expression.
AB  - The extracts of the brown alga, Ascophyllum nodosum, which contains several
      bioactive compounds, have been shown to impart biotic and abiotic stress
      tolerance properties when consumed by animals. However, the physiological,
      biochemical and molecular mechanism underlying such effects remain elusive. We
      investigated the effect of A. nodosum fucose-containing polymer (FCP) on
      tolerance to thermally induced stress using the invertebrate animal model,
      Caenorhabditis elegans. FCP at a concentration of 150 MUg mL(-1) significantly
      improved the life span and tolerance against thermally induced stress in C.
      elegans. The treatment increased the C. elegans survival by approximately 24%,
      when the animals were under severe thermally induced stress (i.e. 35  degrees C)
      and 27% under mild stress (i.e. 30  degrees C) conditions. The FCP induced
      differential expression of genes and proteins is associated with stress response
      pathways. Under thermal stress, FCP treatment significantly altered the
      expression of 65 proteins (54 up-regulated & 11 down-regulated). Putative
      functional analysis of FCP-induced differential proteins signified an association
      of altered proteins in stress-related molecular and biochemical pathways of the
      model worm. 

PMID- 24323435
TI  - Isolation, cultivation and transfection of human keratinocytes.
AB  - Human keratinocytes could be used in the repair of damaged skin, in tissue
      engineering applications, gene therapy and recently, the generation of iPS cells.
      We isolated human keratinocytes from foreskin and subsequently cultured them on
      fibronectin, collagen type I, gelatin and laminin-coated dishes that contained
      three different types of serum-free medium (epilife, KSM or CnT). We developed
      improved conditions for efficient transfection of these human keratinocytes by
      testing three common transfection methods and a GFP plasmid vector. The isolated
      cells showed typical keratinocyte morphology and expressed the epithelial cell
      specific antigen, cytokeratin 14. Collagen type 1, epilife medium and
      lipofectamin 2000 gave the best results for isolation and transfection of human
      keratinocytes. Our protocol can be used as a reproducible, simple and efficient
      method for isolation, cultivation and genetic manipulation of human
      keratinocytes, which may be useful in cell and gene therapy applications. 

PMID- 24323436
TI  - Extensive coronary arterial fistula development in patients with univentricular
      circulation.
AB  - We describe two children, each with a univentricular circulation who had evidence
      of elevated pulmonary arterial pressure at cardiac catheterization. Both children
      developed extensive coronary arterial fistulae detected at cardiac catherization.
      Each child was medically treated with a combination of phosphodiesterase-5
      inhibitor and endothelin antagonist pulmonary vasodilators. The presence of
      chronic hypoxaemia, elevated filling pressures, and the use of pulmonary
      vasodilators may contribute to coronary endothelial dysfunction, which may result
      in coronary vasculopathy. This may necessitate early referral for orthotopic
      cardiac transplantation. (c) 2013 Wiley Periodicals, Inc. 

PMID- 24323437
TI  - WITHDRAWN: Serotonin receptor antagonists for highly emetogenic chemotherapy in
      adults.

PMID- 24323438
TI  - Building foundations for improving health opportunities in sub-Saharan Africa.

PMID- 24323439
TI  - Brain and liver iron accumulation in aceruloplasminemia.

PMID- 24323440
TI  - The midbrain to pons ratio: a simple and specific MRI sign of progressive
      supranuclear palsy.

PMID- 24323441
TI  - Thalamic glutamate/glutamine in restless legs syndrome: increased and related to
      disturbed sleep.

PMID- 24323442
TI  - Opinion & special articles: the lost resident: why resident physicians still need
      mentoring.

PMID- 24323444
TI  - Child neurology: differential diagnosis of a low CSF glucose in children and
      young adults.
AB  - Analysis of CSF is daily routine in patients with acute neurologic disorders like
      CNS infections. In those patients, the finding of a low CSF glucose may influence
      further diagnostic workup and therapeutic choices. The interpretation of a low
      CSF glucose in patients with a chronic neurologic disorder, however, is a less
      common practice. We present a practical overview on the differential diagnosis of
      a low CSF glucose and stress the importance of recognizing a low CSF glucose as
      the diagnostic marker for GLUT1 deficiency syndrome, a treatable neurometabolic
      disorder. 

PMID- 24323445
TI  - Teaching neuroimages: infant with glutaric aciduria type 1 presenting with
      infantile spasms and hypsarrhythmia.
AB  - A 7-month-old boy with glutaric aciduria type 1 (GA1) presented with 1 week of
      clustered flexor spasms. Examination revealed mild axial hypotonia without
      encephalopathy. Video-EEG monitoring revealed hypsarrhythmia and infantile spasms
      (figure, A). MRI showed acute basal ganglia injury (figure, B). After 3 weeks of
      prednisolone treatment, 5-month follow-up showed continued resolution of
      hypsarrhythmia and spasms. 

PMID- 24323446
TI  - Teaching neuroimages: dyspnea as a presenting manifestation of amyloid myopathy.
AB  - A 69-year-old man had dyspnea followed by slowly progressive proximal leg
      weakness over 2 years. He had macroglossia (figure 1). Creatine kinase was 1,378
      U/L. A deltoid biopsy revealed myopathy, denervation atrophy, and congophilic
      deposits around perimysial vessels, indicating amyloid (figure 2). Further workup
      revealed serum monoclonal lambda protein, bone marrow amyloid, and
      cardiomyopathy. Amyloid myopathy, an underrecognized entity, predominantly
      presents with progressive proximal weakness in primary amyloidosis.(1) Dyspnea
      results from cardiomyopathy or respiratory muscle weakness (our patient had
      both). Macroglossia due to amyloid deposition is a helpful clinical clue. The
      patient is on chemotherapy with cyclophosphamide, dexamethasone, and bortezomib,
      which improves prognosis in amyloidosis.(2.) 

PMID- 24323447
TI  - Short-term separation from groups by male Japanese macaques: costs and benefits
      in feeding behavior and social interaction.
AB  - To expand our understanding of fission-fusion behavior and determine its
      variability among primates, studies of both individual-based and group-based
      fission-fusion are necessary. We conducted a parallel tracking study of male and
      female Japanese macaques (Macaca fuscata yakui) during the non-mating season to
      clarify the general features of separate ranging by males of this species, an
      example of fission-fusion behavior, and to reveal its associated costs and
      benefits. Males frequently engaged in short-term separate ranging, leaving the
      company of females and ranging on their own for periods averaging 68 min in
      duration. However, the males did not venture outside the group's home range. When
      ranging separately from the group, males spent more time feeding, particularly on
      fruit, stayed longer in each feeding tree, and fed at a lower rate than when
      ranging with the group. These behavioral changes suggest that males can avoid
      within-group feeding competition by ranging alone. However, this behavior was
      also associated with higher traveling costs, and these separated males were more
      vulnerable to intergroup competition and had fewer opportunities for social
      interaction. The frequency of separate ranging was lower when highly clumped food
      plant species were the main food source. Lower-ranked males, who received more
      aggression when ranging with the group, exhibited a higher frequency of separate
      ranging. This behavioral flexibility with respect to group cohesion may allow
      males to reduce the costs of group living without completely losing the benefits.
      Specifically, by ranging alone, males may acquire sufficient feeding time without
      being disturbed by other group members. Conversely, when ranging with the group,
      males can access grooming partners and advantages in intergroup competition.

PMID- 24323448
TI  - Introduction of a new journal.

PMID- 24323449
TI  - Clinical translation of cerebral preconditioning.

PMID- 24323450
TI  - Treatment with the iron chelator, deferoxamine mesylate, alters serum markers of
      oxidative stress in stroke patients.
AB  - The iron chelator, deferoxamine mesylate (DFO), has shown neuroprotective
      effects, mediated via suppression of iron-induced hydroxyl radical formation, in
      various animal models of ischemic and hemorrhagic stroke. Therefore, the
      objective of this study was to investigate whether DFO can exert similar actions
      in stroke patients, by examining the effects of treatment with DFO on biological
      markers of oxidative stress, namely serum total hydroperoxides and lipoperoxides
      and total radical trapping antioxidant capacity (TRAP), in stroke patients. We
      found that serum levels of peroxides were reduced, and TRAP levels increased
      after a 3-day treatment with DFO (500 mg). These findings provide a preliminary
      proof of concept that DFO can exert potential antioxidant neuroprotective effects
      in stroke patients. Future, larger-scale, randomized, and controlled studies to
      further evaluate the safety and efficacy of DFO in patients with stroke are
      warranted. 

PMID- 24323451
TI  - First-order mathematical modeling of brain swelling in focal cerebral ischemia.
AB  - Edema is an important part of the pathophysiology of stroke. However, it remains
      unclear how brain swelling may influence the progression and measurement of
      infarction after cerebral ischemia. Initial studies in a mouse model of transient
      middle cerebral artery occlusion demonstrated that infarction grew from 24 to 72
      h after stroke onset. Comparison of 24-h versus 72-h brains suggested that tissue
      swelling developed in both infarcted and non-infarcted ipsilateral regions.
      Volumes of infarction differed, depending on the method of calculation: direct,
      indirect, or normalized. A simple first-order model was constructed dividing
      total brain into three subsets, comprising normal contralateral tissue, non
      infarcted ipsilateral tissue, and infarcted ipsilateral tissue. Each subset was
      then defined as a ratio of original volumes plus additional swollen volumes. By
      changing the relative portion of swelling assigned to infarct versus non-infarct,
      our model demonstrated that direct, indirect, and normalized calculations led to
      different thresholds for matching absolute infarct volumes. In this proof-of
      principle study, we described a mathematical model to simulate the distribution
      of brain swelling and infarct development over time. Our findings suggest that
      accurate quantitation of infarct volumes depends on relative distributions of
      edema that may occur in both infarcted as well as non-infarcted brain. 

PMID- 24323453
TI  - Comparison of anti-endotoxin activity of apoE and apoA mimetic derivatives of a
      model amphipathic peptide 18A.
AB  - Endotoxemia is a major cause of chronic inflammation, and is an important
      pathogenic factor in the development of metabolic syndrome and atherosclerosis.
      Human apolipoprotein E (apoE) and apoA-I are protein components of high-density
      lipoprotein, which have strong anti-endotoxin activity. Here, we compared anti
      endotoxin activity of Ac-hE18A-NH2 and 4F peptides, modified from model
      amphipathic helical 18A peptide, to mimic, respectively, apoE and apoA-I
      properties. Ac-hE18A-NH2, stronger than 4F, inhibited endotoxin activity and
      disaggregated Escherichia coli 055:B5 (wild smooth serotype). Ac-hE18A-NH2 and 4F
      inhibited endotoxin activity of E. coli 026:B6 (rough-like serotype) to a similar
      degree. This suggests that Ac-hE18A-NH2 as a dual-domain molecule might interact
      with both the lipid A and headgroup of smooth LPS, whereas 4F binds lipid A. In
      C57BL/6 mice, Ac-hE18A-NH2 was superior to 4F in inhibiting the inflammatory
      responses mediated by E. coli 055:B5, but not E. coli 026:B6. However, in THP-1
      cells, isolated human primary leukocytes, and whole human blood, Ac-hE18A-NH2
      reduced responses more strongly than 4F to both E. coli serotypes either when
      peptides were pre-incubated or co-incubated with LPS, indicating that Ac-hE18A
      NH2 also has strong anti-inflammatory effects independent of endotoxin
      neutralizing properties. In conclusion, Ac-hE18A-NH2 is more effective than 4F in
      inhibiting LPS-mediated inflammation, which opens prospective clinical
      applications for Ac-hE18A-NH2. 

PMID- 24323452
TI  - Protein-bound polysaccharide-K induces IL-1beta via TLR2 and NLRP3 inflammasome
      activation.
AB  - Inflammasome activation has been shown to regulate both innate and adaptive
      immune responses. It is important to investigate whether immune-enhancing natural
      products can also activate inflammasome. The current study examined the potential
      of protein-bound polysaccharide-K (PSK), a hot water extract from Trametes
      versicolor, to activate inflammasome. Using THP-1 cells, we have demonstrated
      that PSK induces both pro-IL-1beta and mature IL-1beta in THP-1 cells in a
      caspase 1- and NLRP3-dependent manner. PSK also induces IL-1beta and IL-18 in
      human PBMC. Cathepsin B is required for PSK-induced inflammasome activation as CA
      074-Me, a cathepsin B inhibitor, significantly decreased PSK-induced IL-1beta.
      PSK induces NLRP3 at both mRNA and protein level. Comparison of PSK-induced IL
      1beta in bone marrow-derived macrophages from wild type C57BL/6 mice, TLR2(-/-),
      P2X7R(-/-) and NLRP3(-/-) mice demonstrated that PSK-induced IL-1beta is
      dependent on both TLR2 and NLRP3. P2X7R is not required for PSK-induced
      inflammasome activation, but enhances PSK-induced caspase-1 activation and IL
      1beta induction. Altogether, these results demonstrated that PSK induces
      inflammasome activation and production of IL-1beta in a TLR2- and NLRP3-dependent
      mechanism. These results provide novel insights into the mechanisms of the immune
      modulatory effects of PSK. 

PMID- 24323454
TI  - The future of targeted peptidomics.
AB  - Targeted MS is becoming increasingly important for sensitive and specific
      quantitative detection of proteins and respective PTMs. In this article, Ceglarek
      et al. [Proteomics Clin. Appl. 2013, 7, 794-801] present an LC-MS-based method
      for simultaneous quantitation of seven apolipoproteins in serum specimens. The
      assay fulfills many necessities of routine diagnostic applications, namely, low
      cost, high throughput, and good reproducibility. We anticipate that validation of
      new biomarkers will speed up with this technology and the palette of laboratory
      based diagnostic tools will hopefully be augmented significantly in the near
      future. 

PMID- 24323455
TI  - Seeing through the trick of cancer cells via 2D gels.
AB  - The advancement of modern therapy concepts has dramatically extended the
      postsurvival rates of patients with malignant gastric cancer. However, a
      remaining setback is the drug resistance of recurrent cancer, which casts a dark
      shadow over disease prognosis. The original work of Klein et al. [Proteomics
      Clin. Appl. 2013, 7, 813-824] has outlined a rational experimental approach to
      decipher the mechanistic pathway of cancer drug resistance by proteomic approach.
      They used gel-based comparative proteomics to analyze the nuclear proteome of a
      human gastric cancer cell line (AGS) with and without inactivation of hypoxia
      inducible factor 1 (HIF-1), a transcription factor and master regulator of
      hypoxia adaptation. Using the classical 2DE-MS approach, these researchers
      observed 163 HIF-1 responsive proteins, among which over half of them could be
      confidently identified by MS. From this large dataset, the authors proposed an
      enhanced nuclear translocation of some proteasomal proteins upon inactivation of
      HIF-1. Overall, this work appropriately used proteomics as a hypothesis-free, top
      down approach to dissect imperative clinical problems. 

PMID- 24323456
TI  - Diagnostic proteomics: will this impact the clinic?

PMID- 24323457
TI  - On best practices: the Institute of Medicine scheme for developing, validating,
      and demonstrating clinical utility of omics-based diagnostic and predictive
      tests.
AB  - The Institute of Medicine of the US National Academy of Sciences issued a major
      report in 2012 that provides important guidance for the proteomics community for
      credible and transparent development of all kinds of omics-based diagnostic and
      prognostic tests. The key elements are summarized here to provide a compass that
      can guide the studies emerging from many laboratories as reported in this special
      issue of Proteomics Clinical Applications on "Diagnostic Proteomics." 

PMID- 24323458
TI  - Plasma protein analysis of patients with different B-cell lymphomas using high
      content antibody microarrays.
AB  - PURPOSE: In this study, plasma samples from a multicentric case-control study on
      lymphoma were analyzed for the identification of proteins useful for diagnosis.
      EXPERIMENTAL DESIGN: The protein content in the plasma of 100 patients suffering
      from the three most common B-cell lymphomas and 100 control samples was studied
      with antibody microarrays composed of 810 antibodies that target cancer
      associated proteins. Sample pools were screened for an identification of marker
      proteins. Then, the samples were analyzed individually to validate the usability
      of these markers. RESULTS: More than 200 proteins with disease-associated
      abundance changes were found. The evaluation on individual patients confirmed
      some molecules as robust informative markers while others were inadequate for
      this purpose. In addition, the analysis revealed distinct subgroups for each of
      the three investigated B-cell lymphoma subtypes. With this information, we
      delineated a classifier that discriminates the different lymphoma entities.
      CONCLUSIONS AND CLINICAL RELEVANCE: Variations in plasma protein abundance permit
      discrimination between different patient groups. After validation on a larger
      study cohort, the findings could have diagnostic as well as differential
      diagnostic potential. Beside this, methodological aspects were critically
      evaluated, such as the value of sample pooling for the identification of
      biomarkers that are useful for a diagnosis on individual patients.

PMID- 24323459
TI  - Identification of a protein signature in renal allograft rejection.
AB  - PURPOSE: Serum creatinine functions as a poor surrogate marker of renal allograft
      dysfunction and long-term graft survival. By measuring multiple proteins
      simultaneously in the serum of transplant patients, we can identify unique
      protein signatures of graft dysfunction. EXPERIMENTAL DESIGN: We utilized
      training and validation cohorts composed of healthy and volunteer subjects,
      stable renal transplant patients, and renal transplant patients experiencing
      acute allograft rejection. Utilizing our antibody microarray, we measured 108
      proteins simultaneously in these groups. RESULTS: Using Mann-Whitney tests with
      Bonferroni correction, we identified ten serum proteins from 19 renal transplant
      patients with stable renal function, which are differentially expressed, compared
      to healthy control subjects. In addition, we identified 17 proteins that
      differentiate rejecting renal transplant recipients from stable renal transplant.
      Validation cohorts substantiated these findings. CONCLUSION AND CLINICAL
      RELEVANCE: Our preliminary results support that a specific pattern of protein
      expression or "protein signature" may be able to differentiate between stable
      transplant patients from those with rejection. Future studies will focus on other
      etiologies of renal allograft dysfunction and the effect of treatment on protein
      expression and long-term outcome.

PMID- 24323463
TI  - Only connect.

PMID- 24323464
TI  - Rice proteomics: a model system for crop improvement and food security.
AB  - Rice proteomics has progressed at a tremendous pace since the year 2000, and that
      has resulted in establishing and understanding the proteomes of tissues, organs,
      and organelles under both normal and abnormal (adverse) environmental conditions.
      Established proteomes have also helped in re-annotating the rice genome and
      revealing the new role of previously known proteins. The progress of rice
      proteomics had recognized it as the corner/stepping stone for at least cereal
      crops. Rice proteomics remains a model system for crops as per its exemplary
      proteomics research. Proteomics-based discoveries in rice are likely to be
      translated in improving crop plants and vice versa against ever-changing
      environmental factors. This review comprehensively covers rice proteomics studies
      from August 2010 to July 2013, with major focus on rice responses to diverse
      abiotic (drought, salt, oxidative, temperature, nutrient, hormone, metal ions, UV
      radiation, and ozone) as well as various biotic stresses, especially rice
      pathogen interactions. The differentially regulated proteins in response to
      various abiotic stresses in different tissues have also been summarized,
      indicating key metabolic and regulatory pathways. We envision a significant role
      of rice proteomics in addressing the global ground level problem of food
      security, to meet the demands of the human population which is expected to reach
      six to nine billion by 2040. 

PMID- 24323465
TI  - Periostin and transforming growth factor beta-induced protein (TGFbetaIp) are
      both expressed by osteoblasts and osteoclasts.
AB  - Periostin (Postn) and transforming growth factor beta-induced protein (TGFbetaIp)
      are two closely related extracellular matrix (ECM) proteins predominantly
      distributed in collagen-rich connective tissues submitted to mechanical strain,
      including bone and more specifically the periosteum. We have investigated the
      expression of Postn and TGFbetaIp mRNA by primary osteoblasts isolated from mouse
      periosteum and calvaria, or by the osteoblast-like MC3T3-E1 cell line, and by
      osteoclasts from mouse long bones differentiated in vitro. Secretion of Postn was
      measured with a specific ELISA. Postn and TGFbetaIp mRNA were concomitantly
      expressed in all three osteoblast models all along the differentiation process in
      a time-dependent manner. Both Postn and TGFbetaIp transcripts appeared early in
      osteoblast differentiation, and their expression increased 3-10 times in mature
      osteoblast cells. Expression decreased after differentiation was achieved and
      when the cultures mineralised. ELISA for secreted Postn showed a similar pattern.
      When MC3T3-E1 cells were treated with TGF-beta, Postn and TGFbetaIp mRNA
      expression and secretion were stimulated, whereas 1.25(OH)(2)D(3) had no
      detectable effect. Osteoclasts also expressed both Postn and TGFbetaIp during in
      vitro differentiation. Expression of both Postn and TGFbetaIp peaks in the early
      phases of osteoblast differentiation, and decreases later at the start of
      mineralisation. A novel finding is that Postn and TGFbetaIp are expressed by
      osteoclasts in vitro. Therefore Postn and TGFbetaIp proteins are potential
      biomarkers of early osteoblast differentiation and new bone formation.

PMID- 24323466
TI  - Expression of Wilms' tumor gene (WT1) is associated with survival in malignant
      pleural mesothelioma.
AB  - INTRODUCTION: Calretinin and Wilms' tumor gene (WT1) are mesothelial markers
      routinely used to confirm the diagnosis of malignant pleural mesothelioma (MPM).
      We investigated the prognostic value of calretinin and WT1 expression in
      predicting survival in a series of patients diagnosed with MPM in our
      institution. MATERIALS AND METHODS: Fifty-two patients diagnosed of MPM were
      retrospectively reviewed. Calretinin and WT1 were stained for IHC analysis in
      formalin-fixed, paraffin-embedded sections and positivity was considered for
      tumors with >1 % of tumor cells stained. Survival data were calculated by the
      Kaplan-Meier method and Cox regression was used to evaluate the prognostic value
      of the variables. RESULTS: Calretinin IHC expression was positive in 83.7 % of
      patients and WT1 in 78.1 %. A significant association of calretinin and WT1
      expression with epithelial histology was detected (p = 0.030 and p = 0.010). We
      found a significant increase in OS in patients with epithelial subtype, PS1 and
      neutrophil-lymphocyte ratio (NLR) <=5 (p < 0.05). In the IHC markers analysis, we
      found a significant increase in OS for patients with WT1 positive expression
      (16.4 vs. 2.3 m, p = 0.013), but not differences for calretinin expression (16.6
      vs. 5.0 months, p = 0.37). In the multivariate analysis, epithelial histology and
      WT1 remained as significant prognostic factors for survival (p = 0.004 and p =
      0.010, respectively). CONCLUSION: In our series of 52 MPM patients, epithelial
      histology, PS, NLR and WT1 expression are significant prognostic factors for
      survival. We concluded that WT1, but not calretinin, is a useful prognostic
      factor in MPM. The role of WT1 assessment is worth of prospective validation in
      future studies on MPM.

PMID- 24323467
TI  - Unraveling the complex maternal history of Southern African Khoisan populations.
AB  - The Khoisan populations of southern Africa are known to harbor some of the
      deepest-rooting lineages of human mtDNA; however, their relationships are as yet
      poorly understood. Here, we report the results of analyses of complete mtDNA
      genome sequences from nearly 700 individuals representing 26 populations of
      southern Africa who speak diverse Khoisan and Bantu languages. Our data reveal a
      multilayered history of the indigenous populations of southern Africa, who are
      likely to be the result of admixture of different genetic substrates, such as
      resident forager populations and pre-Bantu pastoralists from East Africa. We find
      high levels of genetic differentiation of the Khoisan populations, which can be
      explained by the effect of drift together with a partial uxorilocal/multilocal
      residence pattern. Furthermore, there is evidence of extensive contact, not only
      between geographically proximate groups, but also across wider areas. The results
      of this contact, which may have played a role in the diffusion of common cultural
      and linguistic features, are especially evident in the Khoisan populations of the
      central Kalahari.

PMID- 24323468
TI  - Pharmacokinetics of ertapenem in critically ill patients receiving continuous
      venovenous hemodialysis or hemodiafiltration.
AB  - This study characterizes the pharmacokinetics of ertapenem, a carbapenem
      antibiotic, in critically ill adult subjects receiving continuous renal
      replacement therapy (CRRT). Eight critically ill patients with suspected/known
      Gram-negative infections receiving continuous venovenous hemodialysis (CVVHD) or
      continuous venovenous hemodiafiltration (CVVHDF) and ertapenem were enrolled. One
      gram of ertapenem was infused over 30 min. Predialyzer blood samples were drawn
      with the first dose of ertapenem from the hemodialysis tubing at time zero, 30
      min, and 1, 2, 4, 8, 12, 18, and 24 h after the start of the ertapenem infusion.
      Effluent was collected at the same time points. Ertapenem total serum, unbound
      serum, and effluent concentrations from all eight subjects were used
      simultaneously to perform a population compartmental pharmacokinetic modeling
      procedure using NONMEM. Monte Carlo simulations were performed to evaluate the
      ability of several ertapenem dosing regimens (500 mg once daily, 750 mg once
      daily, 500 mg twice daily, and 1,000 mg once daily) to obtain effective unbound
      serum concentrations above 0.5, 1, and 2 MUg/ml. For our simulated patients, all
      regimens produced unbound ertapenem concentrations above 2 MUg/ml for 40% of the
      dosing interval for at least 96% of simulated patients. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT00877370.). 

PMID- 24323469
TI  - Susceptibility of multiresistant gram-negative bacteria to fosfomycin and
      performance of different susceptibility testing methods.
AB  - Fosfomycin may be a treatment option for multiresistant Gram-negative bacteria.
      This study compared susceptibility methods using 94 multiresistant clinical
      isolates. With agar dilution (AD), susceptibilities were 81%, 7%, 96%, and 100%
      (CLSI) and 0%, 0%, 96%, and 30% (EUCAST), respectively, for Acinetobacter
      baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter spp.
      Categorical agreement between Etest and AD for Enterobacteriaceae and A.
      baumannii was >=80%. Disk diffusion was adequate only for Enterobacter. CLSI
      criteria for urine may be adequate for systemic infections. 

PMID- 24323470
TI  - Summary of linezolid activity and resistance mechanisms detected during the 2012
      LEADER surveillance program for the United States.
AB  - This study summarizes the linezolid susceptibility testing results for 7,429 Gram
      positive pathogens from 60 U.S. sites collected during the 2012 sampling year for
      the LEADER Program. Linezolid showed potent activity when tested against 2,980
      Staphylococcus aureus isolates, inhibiting all but 3 at <=2 MUg/ml. Similarly,
      linezolid showed coverage against 99.5% of enterococci, as well as for all
      streptococci tested. These results confirm a long record of linezolid activity
      against U.S. Gram-positive isolates since regulatory approval in 2000. 

PMID- 24323471
TI  - Vaginally delivered tenofovir disoproxil fumarate provides greater protection
      than tenofovir against genital herpes in a murine model of efficacy and safety.
AB  - Increased susceptibility to genital herpes in medroxyprogesterone-treated mice
      may provide a surrogate of increased HIV risk and a preclinical biomarker of
      topical preexposure prophylaxis safety. We evaluated tenofovir disoproxil
      fumarate (TDF) in this murine model because an intravaginal ring eluting this
      drug is being advanced into clinical trials. To avoid the complications of
      surgically inserting a ring, hydroxyethylcellulose (HEC)-stable formulations of
      TDF were prepared. One week of twice-daily 0.3% TDF gel was well tolerated and
      did not result in any increase in HSV-2 susceptibility but protected mice from
      herpes simplex virus 2 (HSV-2) disease compared to mice treated with the HEC
      placebo gel. No significant increase in inflammatory cytokines or chemokines in
      vaginal washes or change in cytokine, chemokine, or mitochondrial gene expression
      in RNA extracted from genital tract tissue was detected. To further evaluate
      efficacy, mice were treated with gel once daily beginning 12 h prior to high-dose
      HSV-2 challenge or 2 h before and after viral challenge (BAT24 dosing). The 0.3%
      TDF gel provided significant protection compared to the HEC gel following either
      daily (in 9/10 versus 1/10 mice, P < 0.01) or BAT24 (in 14/20 versus 4/20 mice, P
      < 0.01) dosing. In contrast, 1% tenofovir (TFV) gel protected only 4/10 mice
      treated with either regimen. Significant protection was also observed with daily
      0.03% TDF compared to HEC. Protection was associated with greater murine cellular
      permeability of radiolabeled TDF than of TFV. Together, these findings suggest
      that TDF is safe, may provide substantially greater protection against HSV than
      TFV, and support the further clinical development of a TDF ring. 

PMID- 24323472
TI  - Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical
      echinocandin-resistant Candida Species and Aspergillus species isolates.
AB  - MK-3118 is as an orally active new antifungal in the early stage of clinical
      development that inhibits the biosynthesis of beta-(1,3)-glucan. We evaluated the
      in vitro activity of this compound against wild-type and echinocandin-resistant
      (ER) isolates containing mutations in the FKS gene(s) of Candida spp. and
      Aspergillus spp. MK-3118 demonstrated enhanced efficacy for most C. albicans and
      C. glabrata ER isolates relative to caspofungin, with decreased MICs and half
      maximal inhibitory concentrations (IC50s). 

PMID- 24323473
TI  - Clinical and bacteriological efficacy of rifampin-streptomycin combination for
      two weeks followed by rifampin and clarithromycin for six weeks for treatment of
      Mycobacterium ulcerans disease.
AB  - Buruli ulcer, an ulcerating skin disease caused by Mycobacterium ulcerans
      infection, is common in tropical areas of western Africa. We determined the
      clinical and microbiological responses to administration of rifampin and
      streptomycin for 2 weeks followed by administration of rifampin and
      clarithromycin for 6 weeks in 43 patients with small laboratory-confirmed Buruli
      lesions and monitored for recurrence-free healing. Bacterial load in tissue
      samples before and after treatment for 6 and 12 weeks was monitored by
      semiquantitative culture. The success rate was 93%, and there was no recurrence
      after a 12-month follow-up. Eight percent had a positive culture 4 weeks after
      antibiotic treatment, but their lesions went on to heal. The findings indicate
      that rifampin and clarithromycin can replace rifampin and streptomycin for the
      continuation phase after rifampin and streptomycin administration for 2 weeks
      without any apparent loss of efficacy. 

PMID- 24323474
TI  - Reversible cysteine protease inhibitors show promise for a Chagas disease cure.
AB  - The cysteine protease cruzipain is essential for the viability, infectivity, and
      virulence of Trypanosoma cruzi, the causative agent of Chagas disease. Thus,
      inhibitors of cruzipain are considered promising anti-T. cruzi chemotherapeutic
      agents. Reversible cruzipain inhibitors containing a nitrile "warhead" were
      prepared and demonstrated 50% inhibitory concentrations (IC50s) as potent as 1 nM
      in baculovirus-generated cruzipain enzyme assays. In epimastigote and
      intracellular amastigote in vitro assays, the most potent compounds demonstrated
      antiparasitic behavior in the 5 to 10 MUM IC50 range; however, trypomastigote
      production from the amastigote form was ~90 to 95% inhibited at 2 MUM. Two key
      compounds, Cz007 and Cz008, with IC50s of 1.1 and 1.8 nM, respectively, against
      the recombinant enzyme were tested in a murine model of acute T. cruzi infection,
      with oral dosing in chow for 28 days at doses from 3 to 50 mg/kg of body weight.
      At 3 mg/kg of Cz007 and 3 mg/kg of Cz008, the blood parasitemia areas under the
      concentration-time curves were 16% and 25% of the untreated group, respectively.
      At sacrifice, 24 days after immunosuppression with cyclophosphamide, parasite
      presence in blood, heart, and esophagus was evaluated. Based on negative
      quantitative PCR results in all three tissues, cure rates in surviving animals
      were 90% for Cz007 at 3 mg/kg, 78% for Cz008 at 3 mg/kg, and 71% for
      benznidazole, the control compound, at 50 mg/kg. 

PMID- 24323475
TI  - Emergence of Escherichia coli sequence type 131 isolates producing KPC-2
      carbapenemase in China.
AB  - Twenty-two KPC-2-producing Escherichia coli isolates were obtained from three
      hospitals in Hangzhou, China, from 2007 to 2011. One isolate, with OmpC porin
      deficiency, exhibited high-level carbapenem resistance. Pulsed-field gel
      electrophoresis showed that few isolates were indistinguishable or closely
      related. Multilocus sequence typing indicated that sequence type 131 (ST131) was
      the predominant type (9 isolates, 40.9%), followed by ST648 (5 isolates), ST405
      (2 isolates), ST38 (2 isolates), and 4 single STs, ST69, ST2003, ST2179, and
      ST744. Phylogenetic analysis indicated that 9 group B2 isolates belonged to
      ST131, and 5 of 11 group D isolates belonged to ST648. Only one group B1 isolate
      and one group A isolate were identified. A representative plasmid (pE1) was
      partially sequenced, and a 7,788-bp DNA fragment encoding Tn3 transposase, Tn3
      resolvase, ISKpn8 transposase, KPC-2, and ISKpn6-like transposase was obtained.
      The blaKPC-2-surrounding sequence was amplified by a series of primers. The PCR
      results showed that 13 isolates were consistent with the genetic environment in
      pE1. It is the first report of rapid emergence of KPC-2-producing E. coli ST131
      in China. The blaKPC-2 gene of most isolates was located on a similar genetic
      structure. 

PMID- 24323476
TI  - In Vitro activity of fosfomycin against Escherichia coli isolated from patients
      with urinary tract infections in Canada as part of the CANWARD surveillance
      study.
AB  - We tested 868 urinary isolates of Escherichia coli collected from 2010 to 2013 as
      part of the Canadian national surveillance study CANWARD against fosfomycin by
      using the Clinical and Laboratory Standards Institute (CLSI) agar dilution method
      with MIC interpretation in accordance with the CLSI M100-S23 (2013) criteria. The
      concentrations of fosfomycin inhibiting 50 and 90% of the isolates were <=1 and 4
      MUg/ml; 99.4% of the isolates were susceptible to fosfomycin. 

PMID- 24323477
TI  - Moxifloxacin pharmacokinetics and pleural fluid penetration in patients with
      pleural effusion.
AB  - The aim of this study was to evaluate the pharmacokinetics and penetration of
      moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve
      patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant
      pleural effusion were enrolled in the study. A single-dose pharmacokinetic study
      was performed after intravenous administration of 400 mg MXF. Serial plasma (PL)
      and pleural fluid (PF) samples were collected during a 24-h time interval after
      drug administration. The MXF concentration in PL and PF was determined by high
      performance liquid chromatography, and main pharmacokinetic parameters were
      estimated. Penetration of MXF in PF was determined by the ratio of the area under
      the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to
      the AUC24 in PL. No statistically significant differences in the pharmacokinetics
      in PL were observed between the two groups, despite the large interindividual
      variability in the volume of distribution, clearance, and elimination half-life.
      The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23+/
      1.31 mg/liter, and it was detected 7.50+/-2.39 h after the initiation of the
      infusion. In patients with malignant effusion, CmaxPF was 2.96+/-1.45 mg/liter,
      but it was observed significantly earlier, at 3.58+/-1.38 h (P<0.001). Both
      groups revealed similar values of AUC24PF (31.83+/-23.52 versus 32.81+/-12.66
      mg.h/liter). Penetration of MXF into PF was similarly good in both patient groups
      (1.11+/-0.74 versus 1.17+/-0.39). Despite similar plasma pharmacokinetics,
      patients with empyema/parapneumonic effusion showed a significant delay in
      achievement of PF maximum MXF levels compared to those with malignant effusion.
      However, in both groups, the degree of MXF PF penetration and the on-site drug
      exposure, expressed by AUC24PF, did not differ according to the type of pleural
      effusion.

PMID- 24323478
TI  - Failure of clindamycin to eradicate infection with beta-hemolytic streptococci
      inducibly resistant to clindamycin in an animal model and in human infections.
AB  - Inducible clindamycin resistance in beta-hemolytic streptococci remains an
      underrecognized phenomenon of unknown clinical significance. We performed an
      evaluation of inducible clindamycin resistance using an animal model as well as
      retrospectively reviewing the charts of patients treated with clindamycin
      monotherapy who were infected with beta-hemolytic streptococci inducibly
      resistant to clindamycin. The neutropenic mouse thigh model of infection was used
      to evaluate the in vivo activity of clindamycin against beta-hemolytic
      streptococci, including isolates susceptible, inducibly resistant, or
      constitutively resistant to clindamycin. The clinical microbiology laboratory
      information system and pharmacy databases were cross-referenced to identify
      patients with infections due to inducibly clindamycin-resistant beta-hemolytic
      streptococci who were treated with clindamycin monotherapy. Medical records of
      these patients were reviewed to evaluate microbiologic and clinical outcomes.
      Inducible clindamycin resistance resulted in impaired killing of beta-hemolytic
      streptococci in the animal model. Though suppressed initially, compared to those
      with constitutive resistance (P=0.0429), by 48 h, colony counts of inducibly
      clindamycin-resistant organisms were similar to those of constitutively resistant
      isolates (P=0.1142). In addition, we identified 8 patients infected with
      inducibly clindamycin-resistant beta-hemolytic streptococci who experienced
      clinical and microbiologic failure when treated with clindamycin monotherapy.
      These patients either improved initially and subsequently failed or never
      responded to clindamycin therapy. We have demonstrated in a murine model of
      infection and from human cases that inducible clindamycin resistance in beta
      hemolytic streptococci is clinically significant. Routine testing and reporting
      by clinical laboratories should be encouraged and alternative antimicrobial
      agents considered when these organisms are encountered in clinical care.

PMID- 24323479
TI  - Side-to-end trigeminal to trigeminal fascicular neurorrhaphy to restore lingual
      sensibility: a new technique.

PMID- 24323480
TI  - Computer-assisted design and computer-assisted modeling technique optimization
      and advantages over traditional methods of osseous flap reconstruction.
AB  - There is increased clinical use of computer-assisted design (CAD) and computer
      assisted modeling (CAM) for osseous flap reconstruction, particularly in the head
      and neck region. Limited information exists about methods to optimize the
      application of this new technology and for cases in which it may be advantageous
      over existing methods of osseous flap shaping. A consecutive series of osseous
      reconstructions planned with CAD/CAM over the past 5 years was analyzed.
      Conceptual considerations and refinements in the CAD/CAM process were evaluated.
      A total of 48 reconstructions were performed using CAD/CAM. The majority of cases
      were performed for head and neck tumor reconstruction or related complications
      whereas the remainder (4%) were performed for penetrating trauma. Defect location
      was the mandible (85%), maxilla (12.5%), and pelvis (2%). Reconstruction was
      performed immediately in 73% of the cases and delayed in 27% of the cases. The
      mean number of osseous flap bone segments used in reconstruction was 2.41. Areas
      of optimization include the following: mandible cutting guide placement,
      osteotomy creation, alternative planning, and saw blade optimization. Identified
      benefits of CAD/CAM over current techniques include the following: delayed
      timing, anterior mandible defects, specimen distortion, osteotomy creation in
      three dimensions, osteotomy junction overlap, plate adaptation, and maxillary
      reconstruction. Experience with CAD/CAM for osseous reconstruction has identified
      tools for technique optimization and cases where this technology may prove
      beneficial over existing methods. Knowledge of these facts may contribute to
      improved use and main-stream adoption of CAD/CAM virtual surgical planning by
      reconstructive surgeons. 

PMID- 24323481
TI  - Microsurgical reconstruction for head and neck cancer in elderly patients.
AB  - The purpose of this study is to review our group of elderly patients and examine
      whether microsurgical reconstruction is safe to perform in these cases. From
      October 2006 to October 2009, 747 patients with head and neck cancer who
      underwent free flap reconstruction were divided into two groups: patients younger
      than 70 years (n = 714) and patients older than 70 years (n = 33). The two groups
      of patients were compared regarding medical comorbidities, medical/surgical
      complications, smoke, and alcohol consumption and outcomes. Two deaths occurred
      in the "elderly" (6% mortality rate) group of patients and two deaths in the
      "young" group of patients (0.28% mortality rate) in the immediate postoperative
      period (15 days postoperatively). Thus, mortality rate had a significant
      difference (p = 0.011) between these two groups. There was no significant
      difference in morbidity between these two groups of patients regarding the rate
      of medical complications, surgical complications, flap failure, and reexploration
      during our 3-month follow-up period. Mortality risk is higher in the elderly
      group of patients. However, there is no significant difference regarding the free
      flap success rate between these two groups. Thorough preoperative evaluation and
      preparation are critical to achieve a favorable outcome in elderly patients. 

PMID- 24323482
TI  - A new computerized morphometric analysis for peripheral nerve study.
AB  - The commonly used methods to quantify axon numbers and mean area include manual
      and semiautomated procedures. The authors introduce a new fully automated method
      of morphometric analysis using ImageJ and Paint.net software to improve
      efficiency and accuracy. A total of six rat sciatic nerves were examined for
      their axon numbers and mean axon area by comparing the manual method or
      semiautomated MetaVue method with the new ImageJ method. It was observed that the
      number of axons for manual counting and ImageJ were 4,630 +/- 403 and 4,779 +/-
      352, respectively, and the difference was not statistically significant (p > 0.5,
      t-test). The mean axon area measured was 13.44 +/- 2.62 um2 for MetaVue and 8.87
      +/- 0.78 um2 for ImageJ, respectively, and the difference was statistically
      significant (p < 0.01, t-test). The standard error and coefficient of variation
      of MetaVue were 1.07 and 0.195; and for ImageJ were 0.32 and 0.087. The authors
      conclude that their new approach demonstrates improved convenience, time
      efficiency, accuracy, and less operator error or bias. 

PMID- 24323483
TI  - The pedicled latissimus dorsi flap in head and neck reconstruction: an old method
      revisited.
AB  - In head and neck cancer patients with significant comorbidities, the
      reconstructive options are limited, and there is a need for a safe alternative
      for microvascular flaps without compromising flap size. During the study period,
      331 head and neck cancer patients were reconstructed with microvascular tissue
      flaps. Ten patients requiring large resections were considered to have high risks
      for long surgery and to be poor candidates for free tissue transfer and thus were
      reconstructed with a subpectorally tunneled pedicled latissimus dorsi (SP-LD)
      flap. The flap was raised simultaneously with the tumor resection and tunneled to
      the head and neck region. The flap was used for reconstruction of oral,
      mandibular, pharyngeal, or neck defects. Median follow-up was 3.6 years. Median
      duration of surgery was 7 hours and 17 minutes, and total hospital stay was 20
      days. During the follow-up, four patients died of their disease and one from
      another cause (median of 329 days). We were able to perform large tumor
      resections with a curative intent and reconstruct major defects in high-risk head
      and neck cancer patients with a SP-LD flap. It possesses many of the
      characteristics of a free flap with the benefits of a shorter operation time and
      less perioperative risk. 

PMID- 24323484
TI  - Technology diffusion in hospitals: a log odds random effects regression model.
AB  - This study identifies the factors that affect the diffusion of hospital
      innovations. We apply a log odds random effects regression model on hospital
      micro data. We introduce the concept of clustering innovations and the
      application of a log odds random effects regression model to describe the
      diffusion of technologies. We distinguish a number of determinants, such as
      service, physician, and environmental, financial and organizational
      characteristics of the 60 Dutch hospitals in our sample. On the basis of this
      data set on Dutch general hospitals over the period 1995-2002, we conclude that
      there is a relation between a number of determinants and the diffusion of
      innovations underlining conclusions from earlier research. Positive effects were
      found on the basis of the size of the hospitals, competition and a hospital's
      commitment to innovation. It appears that if a policy is developed to further
      diffuse innovations, the external effects of demand and market competition need
      to be examined, which would de facto lead to an efficient use of technology. For
      the individual hospital, instituting an innovations office appears to be the most
      prudent course of action.

PMID- 24323485
TI  - Photoprotection of human dermal fibroblasts against ultraviolet light by
      antioxidant combinations present in tomato.
AB  - In the current study, we evaluated and compared, for the first time in a cell
      model, the effect of lycopene alone or in association with various antioxidants
      present in tomato such as alpha-tocopherol or naringenin, on their capacity to
      protect against oxidative stress generated in human dermal fibroblasts (hdf)
      exposed to ultraviolet-A (UVA) light. UVA irradiation of hdf led to a reduced
      cell viability in a dose dependent manner. Similar effects were observed when
      cells were exposed to lycopene. This reduction was suppressed in the presence of
      naringenin but not with alpha-tocopherol. Reactive oxygen species production was
      strongly induced by UVA irradiation. Only co-incubation with naringenin (highest
      level) was able to inhibit this effect. The combination of lycopene : naringenin
      further increased the stability of the carotenoid. Heme-oxygenase 1 (HO-1)
      expression was induced by UVA irradiation but none of the antioxidants inhibited
      this effect at the concentrations used in the study. Indeed, lycopene (1 MUM) led
      to a further 2.5-fold rise in the UVA-induced HO-1 expression. However, this
      effect was suppressed by concomitant addition of naringenin. In our study,
      naringenin prevents oxidative degradation of lycopene. These results strengthen
      the hypothesis that combinations of dietary antioxidants present in tomato other
      than lycopene alone could play a role in the health effects of tomato as
      evidenced by epidemiological studies. 

PMID- 24323486
TI  - Patient exposure to X-rays during coronary angiography and percutaneous
      transluminal coronary intervention: results of a multicenter national survey.
AB  - OBJECTIVES: To evaluate practices for the protection from radiation of patients
      during coronary angiography (CA) and percutaneous coronary intervention (PCI),
      and to update reference values for the main radiation dose parameters.
      BACKGROUND: Few multicenter data from large populations exist on radiation doses
      to patients during CA and PCI. METHODS: RAY'ACT is a multicenter, nationwide
      French survey, with retrospective analysis of radiation parameters routinely
      registered in professional software from 33,937 CAs and 27,826 PCIs performed at
      44 centers from January 1, through December 31, 2010. RESULTS: Kerma-area product
      (KAP) was registered in 91.7% (44/48) of centers and in 91.5% of procedures for
      CA (median, 27.2 Gy.cm(2) , interquartile range [IQR], 15.5-45.2) and 91.1% for
      PCI (median, 56.8 Gy.cm(2) , IQR, 32.8-94.6). Fluoroscopy time was registered in
      87.5% (42/48) of centers and in 83.1% of procedures (median, 3.7 min, IQR, 2.3
      6.3 for CA; 10.3 min, 6.7-16.2 for PCI). Variability across centers was high. Old
      equipment and routine left ventriculography were more common and number of
      registered frames and frame rate were higher in centers delivering high doses.
      The radial route was associated with lower doses than the femoral route (median
      KAP 26.8 Gy.cm(2) [15.1-44.25] vs. 28.1 [16.4-46.9] for CA, respectively; and
      55.6 Gy.cm(2) [32.2-92.1] vs. 59.4 [24.6-99.9] for PCI, respectively; P < 0.01).
      CONCLUSIONS: This survey showed a very high rate of compliance with dose
      registration during CA and PCI in French nonacademic hospitals. Updated
      diagnostic reference values are established for the main dose parameters (KAP, 45
      Gy.cm(2) for CA, 95 Gy.cm(2) for PCI).

PMID- 24323490
TI  - "As flies to wanton boys": dilemmas and dodging in the field of nonhuman animal
      ethics.

PMID- 24323493
TI  - Distortion of homeostatic signaling proteins by simulated microgravity in rat
      hypothalamus: A(16) O/(18) O-labeled comparative integrated proteomic approach.
AB  - Microgravity generates oxidative stress in central nervous system, causing
      distortion of various vital signaling cascades involved in many homeostatic
      functions. Here, we performed comparative (16) O/(18) O labeled integrated
      proteomic strategy to observe the differential expression of signaling proteins
      involved in homeostasis. In this study, rat-tail suspension model is employed to
      induce simulated microgravity in CNS. By wide proteomic analysis, total of 35 and
      97 significantly differentially expressed proteins were found by HPLC/ESI-TOF and
      HPLC-Q-TOF analysis, respectively. Among the total of 132 proteins quantified, 25
      proteins were found related to various signaling cascades. Protein Thy-1, 14-3-3
      gamma, 14-3-3 epsilon, 14-3-3 theta, 14-3-3 eta, and 14-3-3 beta/alpha proteins,
      calmodulin and calcium/calmodulin-dependent protein kinase type-II subunit beta
      were found upregulated under the influence of simulated microgravity. These
      proteins are found involved in disrupting homeostatic pathways like sleep/wake
      cycle, drinking behavior, hypothalamic-pituitary-adrenocortical regulation and
      fight and/or flee actions under stress. Furthermore, MS results for protein Thy-1
      were verified by Western blot analysis showing the quantification accuracy of MS
      instruments. Results presented here will serve as means to understand the
      mechanism of action of microgravity and further reference for future detailed
      study of consequences of microgravity on astronauts and their possible
      countermeasures. 

PMID- 24323492
TI  - Association between changes in weight and cerebral arteries in rats.
AB  - The objective of the study was to gain a better understanding of brain artery
      diameters and anatomical variations for precise modification of cerebral blood
      supply in ischemic stroke models. Sprague-Dawley rats (n = 35) were used for the
      experiment. Rats were perfused and resin replicas of cerebral arteries were
      created using a corrosion casting technique. Resin replicas were measured and
      analyzed for correlation of vessel lumen with animal sex and weight. A strong
      correlation between root of aorta diameter and weight was observed (p < 0.0001).
      We also observed a significant correlation between weight, internal carotid
      arteries, right external carotid artery, and pterygopalatine arteries. For the
      common carotid artery, a significant difference between the left and right
      branches was observed even though there was no association with weight. There was
      no significant association observed between animal sex and vessel size
      independent of weight. A better knowledge of vessel lumen in relation to animal
      sex and weight is essential for adequate blockage of an intracranial artery to
      induce cerebral ischemia in a rat model of stroke. This study provides a viable
      reference for choice of rat size in relation to the size of embolic agents such
      as filaments, microwires, or in vitro thrombus used in ischemic stroke
      experiments. 

PMID- 24323494
TI  - Missing defects? A comparison of microscopic and macroscopic approaches to
      identifying linear enamel hypoplasia.
AB  - Linear enamel hypoplasia (LEH), the presence of linear defects of dental enamel
      formed during periods of growth disruption, is frequently analyzed in physical
      anthropology as evidence for childhood health in the past. However, a wide
      variety of methods for identifying and interpreting these defects in
      archaeological remains exists, preventing easy cross-comparison of results from
      disparate studies. This article compares a standard approach to identifying LEH
      using the naked eye to the evidence of growth disruption observed microscopically
      from the enamel surface. This comparison demonstrates that what is interpreted as
      evidence of growth disruption microscopically is not uniformly identified with
      the naked eye, and provides a reference for the level of consistency between the
      number and timing of defects identified using microscopic versus macroscopic
      approaches. This is done for different tooth types using a large sample of unworn
      permanent teeth drawn from several post-medieval London burial assemblages. The
      resulting schematic diagrams showing where macroscopic methods achieve more or
      less similar results to microscopic methods are presented here and clearly
      demonstrate that "naked-eye" methods of identifying growth disruptions do not
      identify LEH as often as microscopic methods in areas where perikymata are more
      densely packed.

PMID- 24323491
TI  - Implications of immune system in stroke for novel therapeutic approaches.
AB  - Each year, approximately 795,000 people suffer a new or recurrent stroke. About
      610,000 of these are first attacks, and 185,000 are recurrent attacks. Currently,
      the only FDA approved treatment for ischemic stroke is the thrombolytic
      recombinant tissue plasminogen activator (Alteplase), which must be given within
      4.5 h of stroke onset. Beyond this time, apoptotic and inflammatory processes
      greatly diminish the therapeutic benefits of current treatments. While there have
      been many experimental treatments for stroke that showed promising preclinical
      efficacy, these treatments have failed to show efficacy in clinical trials. In
      many of these cases, the preclinical animal studies did not model the clinical
      setting effectively. The injury that occurs following stroke is a dynamic
      process. To effectively treat stroke patients at clinically relevant timepoints,
      it is imperative to understand both the humeral and cell-mediated phenomena that
      occur throughout the body in response to ischemic injury over time. Promising
      experimental therapeutics designed to be given 1 to 2 days following stroke
      require both neuroprotective and anti-inflammatory properties in order to be
      efficacious. 

PMID- 24323495
TI  - Seasonal variation in the length of the daily activity period in buffy-headed
      marmosets (Callithrix flaviceps): an important consideration for the analysis of
      foraging strategies in observational field studies of primates.
AB  - Activity budgets are widely used in primate behavioral studies for the analysis
      of ecological strategies. In some cases, there is considerable seasonal variation
      in the length of the daily activity period. Here, activity budgets from two field
      studies of Callithrix flaviceps were compiled first by the traditional approach
      (proportion of scan sample records) and then by considering the proportion of
      time dedicated to each activity over the 24-hr cycle (adjusted budget). Both
      groups were almost invariably active for at least 1-2 hr less than the daylight
      period, with significantly shorter activity periods during the austral winter,
      when the daylight period was up to 2:35 hr shorter than in the summer. The
      adjustment of activity budgets provided a completely different perspective on
      foraging strategies. Whereas the basic budgets indicated a significant increase
      in foraging and moving during the resource-poor dry season (winter) months, the
      time-adjusted data revealed that the primary strategy was a time-minimizing one,
      with the animals simply spending more time at rest during the longer activity
      periods of summer days. While both groups followed the same pattern of relatively
      short activity periods, there were considerable differences between sites in the
      mean duration of the period in a given month, and in behavior patterns, although
      the analysis of the determining factors was beyond the scope of the present
      study. Overall, the results of the study indicate that the manipulation of the
      duration of the daily activity period may be an integral component of primate
      behavioral strategies, and that this parameter should be taken into account
      systematically when evaluating activity patterns, especially at sites at
      relatively high latitudes where day length may vary considerably over the course
      of the year.

PMID- 24323496
TI  - Increased percentages of T cells producing interleukin-21 in patients with immune
      thrombocytopenic purpura.
AB  - Interleukin (IL)-21, a cytokine which promotes differentiation of Th17,
      follicular helper T cell and B cells, may play an important role in controlling
      the autoimmune process in immune thrombocytopenic purpura (ITP), an acquired
      organ-specific autoimmune hemorrhagic disease. The frequencies of IL-21-producing
      T cells and serum levels of IL-21 were determined by flow cytometry analysis and
      ELISA, respectively, in 24 ITP patients and nine healthy controls. RT-PCR showed
      that the frequencies of circulating IL-21-producing T cells and serum levels of
      IL-21 were significantly higher in ITP patients than that in healthy controls.
      Serum IL-21 and IL-21 expression in patients with ITP significantly decreased
      after therapy, suggesting IL-21 might be important in ITP. 

PMID- 24323497
TI  - Ha ha! versus aha! a direct comparison of humor to nonhumorous insight for
      determining the neural correlates of mirth.
AB  - While humor typically involves a surprising discovery, not all discoveries are
      perceived as humorous or lead to a feeling of mirth. Is there a difference in the
      neural signature of humorous versus nonhumorous discovery? Subjects viewed
      drawings that were uninterpretable until a caption was presented that provided
      either: 1) a nonhumorous interpretation (or insight) of an object from an unusual
      or partial view (UV) or 2) a humorous interpretation (HU) of the image achieved
      by linking remote and unexpected concepts. fMRI activation elicited by the UV
      captions was a subset of that elicited by the humorous HU captions, with only the
      latter showing activity in the temporal poles and temporo-occipital junction
      (linking remote concepts), and medial prefrontal cortex (unexpected reward).
      Mirth may be a consequence of the linking of remote ideas producing high-and
      unexpected-activation in association and classical reward areas. We suggest that
      this process is mediated by opioid activity as part of a system rewarding
      attention to novel information. 

PMID- 24323498
TI  - Auditory responses and stimulus-specific adaptation in rat auditory cortex are
      preserved across NREM and REM sleep.
AB  - Sleep entails a disconnection from the external environment. By and large,
      sensory stimuli do not trigger behavioral responses and are not consciously
      perceived as they usually are in wakefulness. Traditionally, sleep disconnection
      was ascribed to a thalamic "gate," which would prevent signal propagation along
      ascending sensory pathways to primary cortical areas. Here, we compared single
      unit and LFP responses in core auditory cortex as freely moving rats
      spontaneously switched between wakefulness and sleep states. Despite robust
      differences in baseline neuronal activity, both the selectivity and the magnitude
      of auditory-evoked responses were comparable across wakefulness, Nonrapid eye
      movement (NREM) and rapid eye movement (REM) sleep (pairwise differences <8%
      between states). The processing of deviant tones was also compared in sleep and
      wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA)
      was observed following the onset of repetitive tones, and the strength of SSA
      effects (13-20%) was comparable across vigilance states. Thus, responses in core
      auditory cortex are preserved across sleep states, suggesting that evoked
      activity in primary sensory cortices is driven by external physical stimuli with
      little modulation by vigilance state. We suggest that sensory disconnection
      during sleep occurs at a stage later than primary sensory areas. 

PMID- 24323500
TI  - Congenital hypothyroidism and the importance of universal newborn screening.
AB  - Congenital hypothyroidism (CH) is one of the most common preventable causes of
      mental retardation in children. Early diagnosis and treatment prevent the
      devastating outcome of mental retardation. Clinical features of CH are subtle and
      are not evident early in the neonatal period. Therefore, universal newborn
      screening (NS) is effective in detecting CH and implementing early treatment.
      This article reviews the current literature regarding the epidemiology, etiology,
      classification, clinical features, diagnosis of primary CH, and the management of
      abnormal newborn screen as well as treatment and prognosis of primary CH and
      outlines the importance of universal newborn screening in preventing mental
      retardation. 

PMID- 24323499
TI  - Age-related changes to layer 3 pyramidal cells in the rhesus monkey visual
      cortex.
AB  - The effects of normal aging on morphologic and electrophysiologic properties of
      layer 3 pyramidal neurons in rhesus monkey primary visual cortex (V1) were
      assessed with whole-cell, patch-clamp recordings in in vitro slices. In another
      cohort of monkeys, the ultrastructure of synapses in the layers 2-3 neuropil of
      V1 was assessed using electron microscopy. Distal apical dendritic branching
      complexity was reduced in aged neurons, as was the total spine density, due to
      specific loss of mushroom spines from the apical tree and of thin spines from the
      basal tree. There was also an age-related decrease in the numerical density of
      symmetric and asymmetric synapses. In contrast to these structural changes,
      intrinsic membrane, action potential (AP), and excitatory and inhibitory synaptic
      current properties were the same in aged and young neurons. Computational
      modeling using morphologic reconstructions predicts that reduced dendritic
      complexity leads to lower attenuation of voltage outward from the soma (e.g.,
      backpropagating APs) in aged neurons. Importantly, none of the variables that
      changed with age differed in neurons from cognitively impaired versus unimpaired
      aged monkeys. In summary, there are age-related alterations to the structural
      properties of V1 neurons, but these are not associated with significant
      electrophysiologic changes or with cognitive decline.

PMID- 24323501
TI  - An update on sugar transport and signalling in grapevine.
AB  - In addition to their role as a source of reduced carbon, sugars may directly or
      indirectly control a wide range of activities in plant cells, through
      transcriptional and post-translational regulation. This control has been studied
      in detail using Arabidopsis thaliana, where genetic analysis offers many
      possibilities. Much less is known about perennial woody species. For several
      years, various aspects of sugar sensing and signalling have been investigated in
      the grape (Vitis vinifera L.) berry, an organ that accumulates high
      concentrations of hexoses in the vacuoles of flesh cells. Here we review various
      aspects of this topic: the molecular basis of sugar transport and its regulation
      by sugars in grapevine; the functional analysis of several sugar-induced genes;
      the effects of some biotic and abiotic stresses on the sugar content of the
      berry; and finally the effects of exogenous sugar supply on the ripening process
      in field conditions. A picture of complex feedback and multiprocess regulation
      emerges from these data.

PMID- 24323503
TI  - Shade avoidance: phytochrome signalling and other aboveground neighbour detection
      cues.
AB  - Plants compete with neighbouring vegetation for limited resources. In competition
      for light, plants adjust their architecture to bring the leaves higher in the
      vegetation where more light is available than in the lower strata. These
      architectural responses include accelerated elongation of the hypocotyl,
      internodes and petioles, upward leaf movement (hyponasty), and reduced shoot
      branching and are collectively referred to as the shade avoidance syndrome. This
      review discusses various cues that plants use to detect the presence and
      proximity of neighbouring competitors and respond to with the shade avoidance
      syndrome. These cues include light quality and quantity signals, mechanical
      stimulation, and plant-emitted volatile chemicals. We will outline current
      knowledge about each of these signals individually and discuss their possible
      interactions. In conclusion, we will make a case for a whole-plant, ecophysiology
      approach to identify the relative importance of the various neighbour detection
      cues and their possible interactions in determining plant performance during
      competition. 

PMID- 24323504
TI  - Mannitol metabolism in brown algae involves a new phosphatase family.
AB  - Brown algae belong to a phylogenetic lineage distantly related to green plants
      and animals, and are found predominantly in the intertidal zone, a harsh and
      frequently changing environment. Because of their unique evolutionary history and
      of their habitat, brown algae feature several peculiarities in their metabolism.
      One of these is the mannitol cycle, which plays a central role in their
      physiology, as mannitol acts as carbon storage, osmoprotectant, and antioxidant.
      This polyol is derived directly from the photoassimilate fructose-6-phosphate via
      the action of a mannitol-1-phosphate dehydrogenase and a mannitol-1-phosphatase
      (M1Pase). Genome analysis of the brown algal model Ectocarpus siliculosus allowed
      identification of genes potentially involved in the mannitol cycle. Among these,
      two genes coding for haloacid dehalogenase (HAD)-like enzymes were suggested to
      correspond to M1Pase activity, and thus were named EsM1Pase1 and EsM1Pase2,
      respectively. To test this hypothesis, both genes were expressed in Escherichia
      coli. Recombinant EsM1Pase2 was shown to hydrolyse the phosphate group from
      mannitol-1-phosphate to produce mannitol but was not active on the hexose
      monophosphates tested. Gene expression analysis showed that transcription of both
      E. siliculosus genes was under the influence of the diurnal cycle. Sequence
      analysis and three-dimensional homology modelling indicated that EsM1Pases, and
      their orthologues in Prasinophytes, should be seen as founding members of a new
      family of phosphatase with original substrate specificity within the HAD
      superfamily of proteins. This is the first report describing the characterization
      of a gene encoding M1Pase activity in photosynthetic organisms. 

PMID- 24323502
TI  - The heat shock factor family from Triticum aestivum in response to heat and other
      major abiotic stresses and their role in regulation of heat shock protein genes.
AB  - Heat shock factors (Hsfs) play a central regulatory role in acquired
      thermotolerance. To understand the role of the major molecular players in wheat
      adaptation to heat stress, the Hsf family was investigated in Triticum aestivum.
      Bioinformatic and phylogenetic analyses identified 56 TaHsf members, which are
      classified into A, B, and C classes. Many TaHsfs were constitutively expressed.
      Subclass A6 members were predominantly expressed in the endosperm under non
      stress conditions. Upon heat stress, the transcript levels of A2 and A6 members
      became the dominant Hsfs, suggesting an important regulatory role during heat
      stress. Many TaHsfA members as well as B1, C1, and C2 members were also up
      regulated during drought and salt stresses. The heat-induced expression profiles
      of many heat shock protein (Hsp) genes were paralleled by those of A2 and A6
      members. Transactivation analysis revealed that in addition to TaHsfA members
      (A2b and A4e), overexpression of TaHsfC2a activated expression of TaHsp promoter
      driven reporter genes under non-stress conditions, while TaHsfB1b and TaHsfC1b
      did not. Functional heat shock elements (HSEs) interacting with TaHsfA2b were
      identified in four TaHsp promoters. Promoter mutagenesis analysis demonstrated
      that an atypical HSE (GAACATTTTGGAA) in the TaHsp17 promoter is functional for
      heat-inducible expression and transactivation by Hsf proteins. The
      transactivation of Hsp promoter-driven reporter genes by TaHsfC2a also relied on
      the presence of HSE. An activation motif in the C-terminal domain of TaHsfC2a was
      identified by amino residue substitution analysis. These data demonstrate the
      role of HsfA and HsfC2 in regulation of Hsp genes in wheat. 

PMID- 24323505
TI  - RBOH1-dependent H2O2 production and subsequent activation of MPK1/2 play an
      important role in acclimation-induced cross-tolerance in tomato.
AB  - H2O2 and mitogen-activated protein kinase (MAPK) cascades play important
      functions in plant stress responses, but their roles in acclimation response
      remain unclear. This study examined the functions of H2O2 and MPK1/2 in
      acclimation-induced cross-tolerance in tomato plants. Mild cold, paraquat, and
      drought as acclimation stimuli enhanced tolerance to more severe subsequent
      chilling, photooxidative, and drought stresses. Acclimation-induced cross
      tolerance was associated with increased transcript levels of RBOH1 and stress-
      and defence-related genes, elevated apoplastic H2O2 accumulation, increased
      activity of NADPH oxidase and antioxidant enzymes, reduced glutathione redox
      state, and activation of MPK1/2 in tomato. Virus-induced gene silencing of RBOH1,
      MPK1, and MPK2 or MPK1/2 all compromised acclimation-induced cross-tolerance and
      associated stress responses. Taken together, these results strongly suggest that
      acclimation-induced cross-tolerance is largely attributed to RBOH1-dependent H2O2
      production at the apoplast, which may subsequently activate MPK1/2 to induce
      stress responses. 

PMID- 24323506
TI  - The NAC-like gene ANTHER INDEHISCENCE FACTOR acts as a repressor that controls
      anther dehiscence by regulating genes in the jasmonate biosynthesis pathway in
      Arabidopsis.
AB  - ANTHER INDEHISCENCE FACTOR (AIF), a NAC-like gene, was identified in Arabidopsis.
      In AIF:GUS flowers, beta-glucuronidase (GUS) activity was detected in the anther,
      the upper parts of the filaments, and in the pollen of stage 7-9 young flower
      buds; GUS activity was reduced in mature flowers. Yellow fluorescent protein
      (YFP)+AIF-C fusion proteins, which lacked a transmembrane domain, accumulated in
      the nuclei of the Arabidopsis cells, whereas the YFP+AIF fusion proteins
      accumulated in the membrane and were absent in the nuclei. Further detection of a
      cleaved AIF protein in flowers revealed that AIF needs to be processed and
      released from the endoplasmic reticulum in order to function. The ectopic
      expression of AIF-C caused a male-sterile phenotype with indehiscent anthers
      throughout flower development in Arabidopsis. The presence of a repressor domain
      in AIF and the similar phenotype of indehiscent anthers in AIF-C+SRDX plants
      suggest that AIF acts as a repressor. The defect in anther dehiscence was due to
      the down-regulation of genes that participate in jasmonic acid (JA) biosynthesis,
      such as DAD1/AOS/AOC3/OPR3/OPCL1. The external application of JA rescued the
      anther indehiscence in AIF-C and AIF-C+SRDX flowers. In AIF-C+VP16 plants, which
      are transgenic dominant-negative mutants in which AIF is converted to a potent
      activator via fusion to a VP16-AD motif, the anther dehiscence was promoted, and
      the expression of DAD1/AOS/AOC3/OPR3/OPCL1 was up-regulated. Furthermore, the
      suppression of AIF through an antisense strategy resulted in a mutant phenotype
      similar to that observed in the AIF-C+VP16 flowers. The present data suggest a
      role for AIF in controlling anther dehiscence by suppressing the expression of JA
      biosynthesis genes in Arabidopsis. 

PMID- 24323507
TI  - Novel roles of plant RETINOBLASTOMA-RELATED (RBR) protein in cell proliferation
      and asymmetric cell division.
AB  - The retinoblastoma (Rb) protein was identified as a human tumour suppressor
      protein that controls various stages of cell proliferation through the
      interaction with members of the E2F family of transcription factors. It was
      originally thought to be specific to animals but plants contain homologues of Rb,
      called RETINOBLASTOMA-RELATED (RBR). In fact, the Rb-E2F module seems to be a
      very early acquisition of eukaryotes. The activity of RBR depends on
      phosphorylation of certain amino acid residues, which in most cases are well
      conserved between plant and animal proteins. In addition to its role in cell
      cycle progression, RBR has been shown to participate in various cellular
      processes such as endoreplication, transcriptional regulation, chromatin
      remodelling, cell growth, stem cell biology, and differentiation. Here, we
      discuss the most recent advances to define the role of RBR in cell proliferation
      and asymmetric cell division. These and other reports clearly support the idea
      that RBR is used as a landing platform of a plethora of cellular proteins and
      complexes to control various aspects of cell physiology and plant development.

PMID- 24323508
TI  - [Changes in dose and injection pattern in the botulinum toxin long-term therapy
      of facial dyskinesis].
AB  - BACKGROUND: Rare information exists about comparative long-term observations of
      patients with facial movement disorders. This retrospective analysis deals with
      the course of different parameters of injection over the time. METHODS: In this
      study we compared the development of long-term botulinum toxin treatments of
      patients with blepharospasm, hemifacial spasm and synkinesis. 80 patients (n=30
      blepharospasm, n=31 hemifacial spasm, n=19 synkinesis), who had at least 10
      consultations for BTA-injections, were included in the retrospective analysis.
      The development for each entity in total dosage, increase in the number of
      injection points and change in dosages for each point were evaluated. RESULTS:
      The over-all dosage in all 3 clinical disorders and for each single disease
      itself increased continuously over the time. The amount of injection points
      increased in the treatment of hemifacial spasm and synkinesis. The dosage per
      point increased most in blepharospasm between the 1. and 25. injection, but was
      distinctly lower in patients with hemifacial spasm and synkinesis. The increase
      in dosage in blepharospasm is therefore, in contrast to the other indications,
      mostly caused by an increase in dosage per point. In patients with hemifacial
      spasm and synkinesis the escalation of dosage is mainly caused by an increase of
      the number of injection points. CONCLUSION: These new aspects of the dynamic in
      the treatment with botulinum toxin enable the physician to understand better the
      dynamic of these diseases, to optimize treatment protocols.

PMID- 24323510
TI  - Main-chain supramolecular polymers based on orthogonal benzo-21-crown-7/secondary
      ammonium salt and terpyridine/metal ion recognition motifs.
AB  - Orthogonal self-assembly of multiple components represents an efficient strategy
      to afford hierarchical and multifunctional assemblies. Here, we demonstrate the
      orthogonal recognition behaviors between benzo-21-crown-7/secondary ammonium salt
      and terpyridine/metal ions (Fe(2+) or Zn(2+) ) recognition motifs. Main-chain
      supramolecular polymers are subsequently achieved via "one-pot" mixing of the
      three monomers together (heteroditopic monomer 1, homoditopic secondary ammonium
      salt monomer 2, and Fe(BF4 )2 *6H2 O or Zn(OTf)2 ), which are confirmed by (1) H
      NMR, UV-Vis, DOSY, and viscosity measurements. Moreover, different metal ions
      (Fe(2+) or Zn(2+) ) exert considerable effects on the size of the resulting
      supramolecular polymers. Integration of two different types of non-covalent
      interactions renders dynamic and responsive properties for the resulting
      supramolecular polymers, as triggered by a variety of external stimuli such as
      temperature, potassium cation, as well as stronger chelating ligands. Therefore,
      the current work is a prerequisite for the future application of such orthogonal
      assemblies as intelligent supramolecular materials. 

PMID- 24323509
TI  - Effect on caries of restricting sugars intake: systematic review to inform WHO
      guidelines.
AB  - A systematic review of studies in humans was conducted to update evidence on the
      association between the amount of sugars intake and dental caries and on the
      effect of restricting sugars intake to < 10% and < 5% energy (E) on caries to
      inform the updating of World Health Organization guidelines on sugars
      consumption. Data sources included MEDLINE, EMBASE, Cochrane Database, Cochrane
      Central Register of Controlled Trials, Latin American and Caribbean Health
      Sciences, China National Knowledge Infrastructure, Wanfang, and South African
      Department of Health. Eligible studies reported the absolute amount of sugars and
      dental caries, measured as prevalence, incidence, or severity. The review was
      conducted and reported in accordance with the PRISMA statement, and the evidence
      was assessed according to GRADE Working Group guidelines. From 5,990 papers
      identified, 55 studies were eligible - 3 intervention, 8 cohort, 20 population,
      and 24 cross-sectional. Data variability limited meta-analysis. Of the studies,
      42 out of 50 of those in children and 5 out of 5 in adults reported at least one
      positive association between sugars and caries. There is evidence of moderate
      quality showing that caries is lower when free-sugars intake is < 10% E. With the
      < 5% E cut-off, a significant relationship was observed, but the evidence was
      judged to be of very low quality. The findings are relevant to minimizing caries
      risk throughout the life course. 

PMID- 24323511
TI  - Assessment of quality of life as a tool for measuring morbidity due to
      Schistosoma mansoni infection and the impact of treatment.
AB  - Recently, health measurements have broadened to include the assessment of quality
      of life (QOL). This study was conducted to assess whether the short form of the
      World Health Organization (WHO) QOL questionnaire (WHOQOL-BREF) was an effective
      tool for measuring morbidity due to Schistosoma mansoni infection and whether it
      could detect an impact of treatment with praziquantel. A total of 724 adults 18
      85 years of age were enrolled. At baseline, S. mansoni prevalence was 73.2% by
      stool examination and 75.4% by circulating cathodic antigen, and there was no
      association between infection status and WHOQOL-BREF scores. Six months after
      treatment, S. mansoni prevalence was lower and the proportion of persons with
      higher WHOQOL-BREF scores significantly increased among persons who were infected
      at baseline. However, a similar increase was observed in persons not infected at
      baseline. In areas of high prevalence, the WHOQOL-BREF may not be able to detect
      the benefits of schistosomiasis control programs.

PMID- 24323512
TI  - Seroprevalence of Leptospira hardjo in cattle and African buffalos in
      southwestern Uganda.
AB  - Leptospirosis, caused by the spirochete bacterium Leptospira spp. is a zoonosis,
      distributed worldwide and classified as an emerging infectious disease. Fatal
      outcomes to leptospiral infection do occur and the disease can cause abortion and
      other reproductive problems in cattle, goats, and pigs. In humans the symptoms
      range from subclinical infection to acute febrile illness, pulmonary hemorrhage
      and renal failure. Leptospirosis has never been officially reported to the World
      Health Organization (WHO) or the World Animal Health Organization in animals or
      humans in Uganda. However, favorable ecological conditions and suitable animal
      hosts can be found within the country. A commercially available enzyme-linked
      immunosorbent (ELISA) kit was used to screen sera samples from domesticated
      cattle and African buffalo (Syncerus caffer) at two locations in southwestern
      Uganda, collected over a 4-year period. Positive samples were found in both
      cattle and African buffalo samples, from both locations and across the sampling
      period. Overall seroprevalence was 42.39% in African buffalo and 29.35% in
      cattle.

PMID- 24323513
TI  - A loop-mediated isothermal amplification (LAMP) assay for Strongyloides
      stercoralis in stool that uses a visual detection method with SYTO-82 fluorescent
      dye.
AB  - An assay to detect Strongyloides stercoralis in stool specimens was developed
      using the loop-mediated isothermal amplification (LAMP) method. Primers were
      based on the 28S ribosomal subunit gene. The reaction conditions were optimized
      and SYTO-82 fluorescent dye was used to allow real-time and visual detection of
      the product. The product identity was confirmed with restriction enzyme
      digestion, cloning, and sequence analysis. The assay was specific when tested
      against DNA from bacteria, fungi and parasites, and 30 normal stool samples.
      Analytical sensitivity was to < 10 copies of target sequence in a plasmid and up
      to a 10(-2) dilution of DNA extracted from a Strongyloides ratti larva spiked
      into stool. Sensitivity was increased when further dilutions were made in water,
      indicative of reduced reaction inhibition. Twenty-seven of 28 stool samples
      microscopy and polymerase chain reaction positive for S. stercoralis were
      positive with the LAMP method. On the basis of these findings, the assay warrants
      further clinical validation.

PMID- 24323514
TI  - Opportunistic diseases in HIV-infected patients in Gabon following the
      administration of highly active antiretroviral therapy: a retrospective study.
AB  - Opportunistic diseases cause substantial morbidity and mortality to human
      immunodeficiency virus (HIV)-infected patients. Highly active antiretroviral
      therapy (HAART) leading to immune reconstitution is the most effective treatment
      of preventing opportunistic diseases. This retrospective study established an
      epidemiologic profile of opportunistic diseases 10 years after the introduction
      of HAART. The HIV antiretroviral therapy-naive patients matching inclusion
      criteria were included. The primary outcome was the prevalence of opportunistic
      diseases. From January 1, 2002 to September 30, 2010, 654 opportunistic diseases
      were identified in 458 patients. Pulmonary tuberculosis, herpes zoster, cerebral
      toxoplasmosis, oral candidiasis, and severe pneumonia accounted for 22.05%,
      15.94%, 14.19%, 14.19%, and 9.39%, respectively. Cryptococcal meningitis and
      pneumocystosis accounted for 0.44% and 0.21%, respectively. The prevalence of
      opportunistic diseases in Gabon remains high. New guidelines emphasize the
      importance of initiating antiretroviral therapy early to reconstitute the immune
      system, and reduce disease risk, and treat the primary opportunistic infection of
      pulmonary tuberculosis.

PMID- 24323515
TI  - Coinfection with Plasmodium falciparum and Schistosoma haematobium: additional
      evidence of the protective effect of Schistosomiasis on malaria in Senegalese
      children.
AB  - Parasitic infections are associated with high morbidity and mortality in
      developing countries. Several studies focused on the influence of helminth
      infections on malaria but the nature of the biological interaction is under
      debate. Our objective was to undertake a study to explore the influence of the
      measure of excreted egg load caused by Schistosoma haematobium on Plasmodium
      falciparum parasite densities. Ten measures of malaria parasite density and two
      measures of schistosomiasis egg urinary excretion over a 2-year follow-up period
      on 178 Senegalese children were considered. A linear mixed-effect model was
      developed to take data dependence into account. This work showed that children
      with a light S. haematobium infection (1-9 eggs/mL of urine) presented lower P.
      falciparum parasite densities than children not infected by S. haematobium (P <
      0.04). Possible changes caused by parasite coinfections should be considered in
      the anti-helminth treatment of children and in malaria vaccination development.

PMID- 24323516
TI  - The role of landscape composition and configuration on Pteropus giganteus
      roosting ecology and Nipah virus spillover risk in Bangladesh.
AB  - Nipah virus has caused recurring outbreaks in central and northwest Bangladesh
      (the "Nipah Belt"). Little is known about roosting behavior of the fruit bat
      reservoir, Pteropus giganteus, or factors driving spillover. We compared human
      population density and ecological characteristics of case villages and control
      villages (no reported outbreaks) to understand their role in P. giganteus
      roosting ecology and Nipah virus spillover risk. Nipah Belt villages have a
      higher human population density (P < 0.0001), and forests that are more
      fragmented than elsewhere in Bangladesh (0.50 versus 0.32 patches/km(2), P <
      0.0001). The number of roosts in a village correlates with forest fragmentation
      (r = 0.22, P = 0.03). Villages with a roost containing Polyalthia longifolia or
      Bombax ceiba trees were more likely case villages (odds ratio [OR] = 10.8, 95%
      confidence interval [CI] = 1.3-90.6). This study suggests that, in addition to
      human population density, composition and structure of the landscape shared by P.
      giganteus and humans may influence the geographic distribution of Nipah virus
      spillovers.

PMID- 24323518
TI  - Balloon aortic valvuloplasty in high risk aortic stenosis patients with left
      ventricular ejection fractions <20%.
AB  - OBJECTIVES: To determine outcomes following balloon aortic valvuloplasty (BAV) in
      aortic stenosis (AS) patients with a left ventricular ejection fraction (LVEF)
      <20%. BACKGROUND: Severe AS patients with a LVEF <20% are excluded from United
      States (U.S.) transcatheter aortic valve replacement (TAVR) trials and often
      surgical aortic valve replacement (AVR). The role for BAV to enhance LVEF is
      unclear. METHODS: Our BAV database of 270 consecutive patients extending from
      2005 through 2010 was queried for a preoperative LVEF <20%. Demographics,
      echocardiograms, procedural technique, and outcomes were analyzed. Pre- and
      postoperative echocardiograms were used to determine improvement in aortic valve
      area (AVA) and LVEF. RESULTS: Sixteen patients were identified with a median age
      of 82 years. The composite Society of Thoracic Surgeons' (STS) mortality risk was
      16.4%. The median preoperative AVA and LVEF were 0.60 cm(2) and 16%,
      respectively, and postoperative AVA and LVEF were 0.77 cm(2) and LVEF 19%,
      respectively. About 15 of the 16 patients had postoperative echocardiograms
      available for comparison. And 7 of these 15 (47%) demonstrated improvement in
      LVEF to >=20% (median LVEF 25%). The absence of coronary disease and improvement
      in AVA of >=0.2 cm(2) was associated with postoperative LVEF of >=20%. Procedural
      mortality was 0%. The 30-day, 6-month, and 1-year survival was 69%, 56%, and 29%.
      STS's mortality risk score >=15% was associated with short-term mortality.
      CONCLUSION: With appropriate technique, BAV can be reasonably safe in patients
      with LVEF <20%. Roughly half of these patients demonstrated improvement in LVEF
      to >=20%.

PMID- 24323519
TI  - Poly(ethylene glycol)-based ionic liquids: properties and uses as alternative
      solvents in organic synthesis and catalysis.
AB  - PEG-based ionic liquids are a new appealing group of solvents making the link
      between two distinct but very similar fluids: ionic liquids and poly(ethylene
      glycol)s. They find applications across a range of innumerable disciplines in
      science, technology, and engineering. In the last years, the possibility to use
      these as alternative solvents for organic synthesis and catalysis has been
      increasingly explored. This Review highlights strategies for their synthesis,
      their physical properties (critical point, glass transition temperature, density,
      rheological properties), and their application in reactions catalyzed by metals
      (such as Pd, Cu, W, or Rh) or as organic solvent (for example for multicomponent
      reactions, organocatalysis, CO2 transformation) with special emphasis on their
      toxicity, environmental impact, and biodegradability. These aspects, very often
      neglected, need to be considered in addition to the green criteria usually
      considered to establish ecofriendly processes. 

PMID- 24323517
TI  - Health care utilization and access to human immunodeficiency virus (HIV) testing
      and care and treatment services in a rural area with high HIV prevalence, Nyanza
      Province, Kenya, 2007.
AB  - We present health and demographic surveillance system data to assess associations
      with health care utilization and human immunodeficiency virus (HIV) service
      receipt in a high HIV prevalence area of western Kenya. Eighty-six percent of
      15,302 residents indicated a facility/clinician for routine medical services; 60%
      reported active (within the past year) attendance. Only 34% reported a previous
      HIV test, and self-reported HIV prevalence was 6%. Active attendees lived only
      slightly closer to their reported service site (2.8 versus 3.1 km; P < 0.001)
      compared with inactive attendees. Multivariate analysis showed that younger
      respondents (< 30 years of age) and active and inactive attendees were more
      likely to report an HIV test compared with non-attendees; men were less likely to
      report HIV testing. Despite traveling farther for HIV services (median distance =
      4.4 km), 77% of those disclosing HIV infection reported HIV care enrollment. Men
      and younger respondents were less likely to enroll in HIV care. Socioeconomic
      status was not associated with HIV service use. Distance did not appear to be the
      major barrier to service receipt. The health and demographic surveillance system
      data identified patterns of service use that are useful for future program
      planning.

PMID- 24323520
TI  - Invited editorial: current impediments to successful translational research in
      stroke.

PMID- 24323521
TI  - Preconditioning the human brain: practical considerations for proving cerebral
      protection.
AB  - Ischemic preconditioning has evolved as one of the most powerful strategies for
      cerebral protection in laboratory models of ischemia. Translating the success of
      laboratory studies to human cerebral protection will necessitate an approximation
      of laboratory conditions. This would require a practical, easily implemented
      method of preconditioning and clinical settings in which cerebral ischemia is
      anticipated, thereby allowing cerebral preconditioning prior to ischemia onset.
      Remote limb ischemic preconditioning is readily instituted and used in several
      ongoing cardiac studies for ischemic myocardial protection. It is a potentially
      promising intervention for brain protection as well. Suitable clinical settings,
      in which a preliminary study of ischemic preconditioning in neurological
      disorders appears feasible, include carotid endarterectomy or stenting, cardiac
      surgery, and subarachnoid hemorrhage with the accompanying risk of vasospasm.
      These are settings, in which there is substantial risk of brain ischemia, which
      occurs over a short and predictable period, allowing for preconditioning to be
      implemented prior to ischemia onset. 

PMID- 24323522
TI  - A Pilot Trial of Low-Dose Intravenous Abciximab and Unfractionated Heparin for
      Acute Ischemic Stroke: Translating GP IIb/IIIa Receptor Inhibition to Clinical
      Practice.
AB  - Thrombolysis remains a mainstay in the treatment of ischemic stroke. While not
      usually considered in the spectrum of clot lysis, experimental data show that
      inhibition of the platelet glycoprotein (GP) IIb/IIIa receptor can reduce as well
      as reverse thrombus formation and improve microvascular flow in stroke models.
      However, a recent clinical trial of GP IIb/IIIa inhibition in stroke did not
      demonstrate clinical benefit and was associated with increased hemorrhage. Based
      on an understanding of the relationship between GP IIb/IIIa receptor inhibition,
      efficacy and hemorrhage, we hypothesized that a lower dose of abciximab would
      achieve a favorable range of platelet inhibition and potentially good clinical
      outcomes. Forty-four patients with suspected large vessel occlusion, who were not
      eligible for rt-PA were offered treatment with approximately 30% lower total dose
      of intravenous abciximab if within 6 h for anterior circulation or 24 h for
      posterior circulation stroke (later modified to 12 h). Concomitant
      anticoagulation, usually with unfractionated heparin was employed. The extent of
      platelet inhibition was measured in 21 patients. Hemorrhage rate and 90-day
      functional outcomes and mortality were obtained. A matching algorithm involving
      finding the nearest neighbor from individual subjects in the control arm of the
      NINDS rt-PA database was used to compare outcomes at similar baseline
      characteristics and gender. Mean platelet inhibition was 92.1 +/- 6.7% vs
      inhibition reported with percutaneous coronary intervention (PCI) of 96 +/- 10; p
      = 0.08. Successful matching to NINDS controls was accomplished: after outlier
      elimination, median and mean NIHSS of the abciximab subjects compared to NINDS
      controls was 16.5 vs 15.5 (p = 0.92) and 16.3 vs 16.0 (p = 0.86). Mean age was
      67.2 vs 67.1 (p = 0.97). Mean glucose was 141 vs 142 (p = 0.92). There was one
      symptomatic hemorrhage; minor hemorrhages occurred in 9%. The percent of patients
      who achieved an mRS 0-2 or died in the treated vs matched NINDS control patients
      was 63 vs 38 (p = .02) and 23 vs 23 (p = 1.0). Our pilot results indicated that a
      lower dose of abciximab results in platelet inhibition similar to that achieved
      in the coronary vascular bed during PCI. Comparison to matched historical
      controls suggests that this lower dose in combination therapy may be safe and
      effective therapy for thrombotic stroke and a randomized trial is warranted. 

PMID- 24323523
TI  - Evidence for a predominant intrinsic sympathetic control of cerebral blood flow
      alterations in an animal model of cerebral arteriovenous malformation.
AB  - In terms of neurogenic cerebral blood flow (CBF) control, the activity of the
      sympathetic nervous system (SNS) has a regulating effect. The impact of a
      manipulation of both the peripheral (via the perivascular sympathetic net) and
      central components (via the intracortical noradrenergic terminals originating
      from the locus coeruleus) on CBF-and especially on hyperperfusion syndromes-is
      unclear. To test the specific patterns following such alterations, cortical
      oxygen saturation (rSO2), regional CBF (rCBF), and cortical interstitial
      norepinephrine (NE) concentrations were measured. Twelve weeks after either the
      creation of an extracranial AV fistula or sham operation, 80 male Sprague-Dawley
      rats underwent one of the following procedures: (1) no SNS manipulation, (2)
      peripheral SNS inhibition via bilateral sympathectomy, (3) central SNS inhibition
      via the neurotoxin DSP-4, or (4) complete SNS inhibition. Norepinephrine
      concentrations were lowest after complete inhibition (NE [nmol]: pre, 1.8 +/-
      1.2; post, 2.4 +/- 1.8) and highest following peripheral inhibition (NE [nmol]:
      pre, 3.6 +/- 1.9; post, 6.6 +/- 4.4). Following fistula occlusion, rCBF (laser
      Doppler unit [LDU]) and rSO2 (%SO2) increases were highest after complete
      inhibition (pre: 204 +/- 14 LDU, 34 +/- 3%SO2; post: 228 +/- 18 LDU, 39 +/-
      3%SO2) and lowest after peripheral inhibition (pre: 221 +/- 18 LDU, 41 +/- 2%SO2;
      post: 226 +/- 14 LDU, 47 +/- 2%SO2). Thus, a complete inhibition down-regulates
      SNS activity and provokes a cortical hyperperfusion condition. With this, the
      hitherto unknown predominant role of the intrinsic component could be
      demonstrated for the first time in vivo. 

PMID- 24323524
TI  - Machine learning applications in proteomics research: how the past can boost the
      future.
AB  - Machine learning is a subdiscipline within artificial intelligence that focuses
      on algorithms that allow computers to learn solving a (complex) problem from
      existing data. This ability can be used to generate a solution to a particularly
      intractable problem, given that enough data are available to train and
      subsequently evaluate an algorithm on. Since MS-based proteomics has no shortage
      of complex problems, and since publicly available data are becoming available in
      ever growing amounts, machine learning is fast becoming a very popular tool in
      the field. We here therefore present an overview of the different applications of
      machine learning in proteomics that together cover nearly the entire wet- and dry
      lab workflow, and that address key bottlenecks in experiment planning and design,
      as well as in data processing and analysis. 

PMID- 24323525
TI  - Differences in early complications between circular and linear stapled
      gastrojejunostomy in laparoscopic gastric bypass.
AB  - BACKGROUND: Laparoscopic gastric bypass (LGBP) is the most common bariatric
      procedure worldwide. The gastrojejunostomy can be stapled with a circular or
      linear stapler, each with their own specific advantages. We have evaluated
      differences in postoperative complications between the two techniques. METHODS:
      We studied operative data and postoperative complications in 560 patients (79.8 %
      females, median age 42, BMI 42.5) operated with LGBP between 2008 and 2012 at our
      center. The gastrojejunostomy was initially performed using a circular stapler
      (CS) in 288 patients and later by linear stapler (LS) in 272. Complications,
      operative time, and length of stay were retrieved from our database. The risk of
      developing a port site infection was evaluated with multivariate logistic
      regression. RESULTS: Port site infections were more common with CS than LS, 5.2
      and 0.4 %, respectively (p < 0.01). Multivariate analysis demonstrated CS to be
      an independent risk factor for port site infections (OR 16.3 (2.09-126), p <
      0.01), as well as for stomal ulcers (OR 10.1, 1.15-89, p = 0.04). Major
      postoperative complications remained unchanged (anastomotic leak 1.0 vs. 1.1 %,
      abscess 0.7 vs. 0.4 %), while operative time and length of stay were found to be
      shorter using the LS (122 vs. 83 min, p < 0.001 and 4 vs. 3 days, p < 0.001).
      CONCLUSIONS: The linear stapled technique yielded lower incidence of port site
      infections, probably by avoiding the passage of a contaminated circular stapler
      through the abdominal wall. No difference in major complications was seen, but
      operative time was shorter using a linear stapler instead of a circular stapler.

PMID- 24323526
TI  - Premature termination of treatment for anorexia nervosa: differences between
      patient-initiated and staff-initiated discharge.
AB  - OBJECTIVES: To investigate treatment drop-out by comparing clinical indicators of
      patients whose discharge was initiated by staff with those who initiated
      discharge themselves. METHOD: Ninety participants with anorexia completed
      questionnaires at admission and four weeks into hospitalized treatment. Weight
      data was collected over this same period. At discharge, participants were
      categorized into completer (n = 38) or patient-initiated (n = 36) /staff
      initiated (n = 16) premature termination groups. RESULTS: Significant differences
      between staff-initiated and patient-initiated discharge groups were found at
      admission. Staff initiated groups were on average older (p = .035), and more
      likely to have had prior compelled treatment (p = .039). At 4 weeks those in the
      patient-initiated group had put on weight at a faster rate (p = .032) and
      reported a decrease in alliance (p = .017). At discharge, staff initiated
      discharge demonstrated greater time in treatment (p = .001), greater weight gain
      (p = .027), and a higher discharge BMI (p = .013). At discharge, staff-initiated
      drop-outs had comparable end-of-treatment outcomes to those who completed
      treatment as planned. DISCUSSION: There are key differences between those who
      prematurely discharge themselves from treatment, compared to those who are
      prematurely discharged by clinical staff. Future research into drop-out needs to
      take into account and recognize these differences.

PMID- 24323527
TI  - Eating disorder examination questionnaire: factor structure for adolescent girls
      and boys.
AB  - OBJECTIVE: To examine the factor structure of the EDE-Q among a sample of
      adolescents. METHOD: A community-based sample of 917 adolescents (522 girls and
      395 boys) aged 14-18 years completed the EDE-Q version 6.0 as part of a larger
      study. Participants were randomly assigned to one of two subsamples to enable
      separate analyses. RESULTS: A confirmatory factor analysis on the original four
      factor model of the EDE-Q produced an inadmissible model with a poor fit.
      Exploratory factor analysis using principal axis factoring produced an
      alternative three factor model of the EDE-Q among adolescents. The Shape and
      Weight Concerns, Restriction and Preoccupation and Eating Concern subscales
      accounted for 65% of the total variance. Subscale and global scores were
      significantly higher for girls than for boys. A high proportion of both girls
      (53.6%) and boys (30.5%) reported participating in at least one key eating
      disordered behaviour during the previous 28 days. DISCUSSION: The results of this
      study present three new subscales (Shape and Weight Concerns, Restriction and
      Preoccupation and Eating Concern) which are suggested for use in future research
      which uses the EDE-Q with community samples of adolescents.

PMID- 24323528
TI  - Treatment of anorexia nervosa in the context of transsexuality: a case report.
AB  - Males comprise a minority of patients with eating disorders (ED). However, men
      who have sex with men, males with gender identity disorder, and transsexual (TS)
      males are at increased risk for ED. Little has been published about the unique
      treatment needs of TS patients with ED. A 19-year-old male-to-female TS patient
      presented with restrictive eating, purging, and weight loss. History revealed
      that her ED ideation and behaviors were strongly intertwined with her gender
      identity. She was admitted and during her hospitalization both her ED and TS
      status were addressed medically. Physicians treating patients with ED should be
      aware of patients' gender identities and the ways in which gender identity may
      impact management and recovery. When appropriate, providers should consider
      addressing medical treatment toward gender transition concurrently with treatment
      for ED to facilitate medical stabilization and weight restoration in the manner
      most consistent with the patient's identified gender.

PMID- 24323529
TI  - Proceedings of the eighty-second meeting of the American Association of Physical
      Anthropologists, Knoxville Convention Center, Knoxville, Tennessee, April 10-13,
      2013.

PMID- 24323530
TI  - Role of chaperone-mediated autophagy in degrading Huntington's disease-associated
      huntingtin protein.
AB  - Mutant N-terminal huntingtin (Htt) protein resulting from Huntington's disease
      (HD) with expanded polyglutamine accumulates and forms aggregates in vulnerable
      neurons. Both ubiquitin proteasomal and autophagic pathways contribute to the
      degradation of mutant Htt. Here, we focus on the involvement of chaperone
      mediated autophagy (CMA), a selective form of autophagy in the clearance of Htt.
      Selective catabolism in CMA is conferred by the presence of a KFERQ-like
      targeting motif in the substrates, by which molecular chaperones recognize the
      hydrophobic surfaces of the misfolded substrates, and transfer them to the
      lysosomal membrane protein type-2A, LAMP-2A. The substrates are taken into the
      lysosomes through LAMP-2A and are rapidly degraded by the lysosomal enzymes.
      Taken together, we summarize the recent evidence to elucidate that Htt is also a
      potential substrate of CMA. We propose that the manipulation of CMA could be a
      therapeutic strategy for HD.

PMID- 24323531
TI  - Preparation of polyclonal antibody highly specific for mouse BRD7 protein and its
      application.

PMID- 24323532
TI  - Commentary.

PMID- 24323533
TI  - Irukandji jellyfish polyps exhibit tolerance to interacting climate change
      stressors.
AB  - Increasing ocean temperatures and strengthening boundary currents have caused the
      poleward migration of many marine species. Cubozoan jellyfish known to cause
      Irukandji syndrome have historically been confined to tropical waters but may be
      expanding into subtropical regions. Here, we examine the interactive effects of
      warming and acidification on the population dynamics of polyps of an Irukandji
      jellyfish, Alatina nr mordens, and the formation of statoliths in newly
      metamorphosed medusae, to determine if this jellyfish could tolerate future
      conditions predicted for southeast Queensland (SEQ), Australia. Two experiments,
      examining the orthogonal factors of temperature and pH, were undertaken.
      Experiment 1 mimicked the current, ca. 2050 and ca. 2100 summer temperature and
      pH conditions predicted for SEQ using A1F1 scenarios (temperature: 25, 27, 29 
      degrees C; pH: 7.9, 7.8, 7.6) and Experiment 2 mimicked current and future winter
      conditions (18 and 22  degrees C, pH 7.9, 7.8, 7.6). All polyps in Experiment 1
      survived and budded. Fewer polyps budded in the lower pH treatments; however,
      patterns varied slightly among temperature treatments. Statoliths at pH 7.6 were
      24% narrower than those at pH 7.8 and 7.9. Most polyps survived the winter
      conditions mimicked by Experiment 2 but only polyps in the 22  degrees C, pH 7.9
      treatment increased significantly. The current absence of A. nr mordens medusae
      in SEQ, despite the polyps' ability to tolerate the current temperature and pH
      conditions, suggests that ecological, rather than abiotic factors currently limit
      their distribution. Observations that budding was lower under low pH treatments
      suggest that rates of asexual reproduction will likely be much slower in the
      future. We consider that A. nr mordens polyps are likely to tolerate future
      conditions but are unlikely to thrive in the long term. However, if polyps can
      overcome potential ecological boundaries and acidification proceeds slowly A. nr
      mordens could expand polewards in the short term. 

PMID- 24323534
TI  - Multi-decadal range changes vs. thermal adaptation for north east Atlantic
      oceanic copepods in the face of climate change.
AB  - Populations may potentially respond to climate change in various ways including
      moving to new areas or alternatively staying where they are and adapting as
      conditions shift. Traditional laboratory and mesocosm experiments last days to
      weeks and thus only give a limited picture of thermal adaptation, whereas ocean
      warming occurring over decades allows the potential for selection of new strains
      better adapted to warmer conditions. Evidence for adaptation in natural systems
      is equivocal. We used a 50-year time series comprising of 117 056 samples in the
      NE Atlantic, to quantify the abundance and distribution of two particularly
      important and abundant members of the ocean plankton (copepods of the genus
      Calanus) that play a key trophic role for fisheries. Abundance of C.
      finmarchicus, a cold-water species, and C. helgolandicus, a warm-water species,
      were negatively and positively related to sea surface temperature (SST)
      respectively. However, the abundance vs. SST relationships for neither species
      changed over time in a manner consistent with thermal adaptation. Accompanying
      the lack of evidence for thermal adaptation there has been an unabated range
      contraction for C. finmarchicus and range expansion for C. helgolandicus. Our
      evidence suggests that thermal adaptation has not mitigated the impacts of ocean
      warming for dramatic range changes of these key species and points to continued
      dramatic climate induced changes in the biology of the oceans. 

PMID- 24323535
TI  - Chilling outweighs photoperiod in preventing precocious spring development.
AB  - It is well known that increased spring temperatures cause earlier onset dates of
      leaf unfolding and flowering. However, a temperature increase in winter may be
      associated with delayed development when species' chilling requirements are not
      fulfilled. Furthermore, photosensitivity is supposed to interfere with
      temperature triggers. To date, neither the relative importance nor possible
      interactions of these three factors have been elucidated. In this study, we
      present a multispecies climate chamber experiment to test the effects of chilling
      and photoperiod on the spring phenology of 36 woody species. Several hypotheses
      regarding their variation with species traits (successional strategy, floristic
      status, climate of their native range) were tested. Long photoperiods advanced
      budburst for one-third of the studied species, but magnitudes of these effects
      were generally minor. In contrast to prior hypotheses, photosensitive responses
      were not restricted to climax or oceanic species. Increased chilling length
      advanced budburst for almost all species; its effect greatly exceeding that of
      photoperiod. Moreover, we suggest that photosensitivity and chilling effects have
      to be rigorously disentangled, as the response to photoperiod was restricted to
      individuals that had not been fully chilled. The results indicate that
      temperature requirements and successional strategy are linked, with climax
      species having higher chilling and forcing requirements than pioneer species.
      Temperature requirements of invasive species closely matched those of native
      species, suggesting that high phenological concordance is a prerequisite for
      successful establishment. Lack of chilling not only led to a considerable delay
      in budburst but also caused substantial changes in the chronological order of
      species' budburst. The results reveal that increased winter temperatures might
      impact forest ecosystems more than formerly assumed. Species with lower chilling
      requirements, such as pioneer or invasive species, might profit from warming
      winters, if late spring frost events would in parallel occur earlier. 

PMID- 24323536
TI  - Radiolucent lesions of the mandible: a pattern-based approach to diagnosis.
AB  - OBJECTIVES: Radiolucent mandibular lesions seen on panoramic radiographs develop
      from both odontogenic and non-odontogenic structures. They represent a broad
      spectrum of lesions with a varying degree of malignant potential. The purpose of
      this review is to illustrate the characteristic imaging findings-as well as the
      clinical and histological features-of common and uncommon radiolucent lesions of
      the mandible. METHODS: This review article is based on the retrospective
      evaluation of 11,725 panoramic radiographs seen in our institution during the
      past 6 years. It provides a comprehensive, practical approach to the radiological
      interpretation of radiolucent lesions of the mandible. To facilitate the
      diagnostic approach, we have classified radiolucent lesions into two groups:
      lesions with well-defined borders and those with ill-defined borders. RESULTS:
      Lesion prevalence, age of manifestation, location within the mandible,
      relationship to dental structures, effect on adjacent structures and
      characteristic findings at computed tomography (CT), cone beam CT (CBCT) and
      magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) are
      discussed. Pitfalls including malignant lesions mimicking benign disease and
      pseudo-lesions are equally addressed. CONCLUSION: Knowledge of the characteristic
      imaging features of radiolucent mandibular lesions narrows the differential
      diagnosis and is crucial for the identification of those lesions, where biopsy is
      indicated for definitive histology. TEACHING POINTS: * Panoramic X-rays, CT and
      MRI are essential for the work-up of radiolucent mandibular lesions. * Lesion
      borders, location within the mandible, relationship to dental structures and
      tissue characteristics on cross-sectional imaging are indispensable to narrow the
      differential diagnosis. * High-resolution CT and CBCT play a major role for the
      assessment of lesion margins and their relationship to important anatomic
      structures, such as the inferior alveolar nerve. * Although most radiolucent
      lesions with well-defined sclerotic borders are benign, MRI may reveal clinically
      unsuspected malignant disease.

PMID- 24323537
TI  - Cell-loaded gelatin/chitosan scaffolds fabricated by salt-leaching/lyophilization
      for skin tissue engineering: in vitro and in vivo study.
AB  - In this study, physical and biological features of the novel three-dimensional
      cell-loaded gelatin (G)/chitosan (CS) scaffolds fabricated via combining salt
      leaching and lyophilization technique is evaluated. To fabricate these scaffolds,
      CS and G solutions were blended at different ratios and the influence of G/CS
      ratio on physical and biological properties of the scaffolds were studied. The
      properties of porous structure, such as microstructure, porosity, mean pore size,
      phosphate buffer saline solution absorption, mechanical properties as well as
      biocompatibility were evaluated. The in vitro assays showed excellent cell
      attachment and proliferation on scaffolds with G/CS ratio of 80/20. The results
      showed that the amount of G has a significant effect on attachment, growth, and
      proliferation of fibroblast cells on the scaffolds. In vivo assessment showed
      that treatment with human dermal fibroblast cell loaded scaffolds significantly
      accelerated wounds healing in rat compared with the control groups. The
      biological investigation on these scaffolds proves that they have a great
      potential for using in skin tissue engineering.

PMID- 24323538
TI  - Curcumin: therapeutical potential in ophthalmology.
AB  - Curcumin (diferuloylmethane) is the main curcuminoid of the popular Indian spice
      turmeric (Curcuma longa). In the last 50 years, in vitro and in vivo experiments
      supported the main role of polyphenols and curcumin for the prevention and
      treatment of many different inflammatory diseases and tumors.The anti
      inflammatory, antioxidant, and antitumor properties of curcumin are due to
      different cellular mechanisms: this compound, in fact, produces different
      responses in different cell types. Unfortunately, because of its low solubility
      and oral bioavailability, the biomedical potential of curcumin is not easy to
      exploit; for this reason more attention has been given to nanoparticles and
      liposomes, which are able to improve curcumin's bioavailability.
      Pharmacologically, curcumin does not show any dose-limiting toxicity when it is
      administered at doses of up to 8 g/day for three months. It has been demonstrated
      that curcumin has beneficial effects on several ocular diseases, such as chronic
      anterior uveitis, diabetic retinopathy, glaucoma, age-related macular
      degeneration, and dry eye syndrome. The purpose of this review is to report what
      has so far been elucidated about curcumin properties and its potential use in
      ophthalmology.

PMID- 24323539
TI  - Reticular and myxoid non-keratinizing nasopharyngeal carcinoma: an unusual case
      mimicking a salivary gland carcinoma.
AB  - We present a case of non-keratinizing carcinoma of the nasopharynx (NK-NPC) with
      an unusual histopathological pattern. The neoplastic cells were arranged in
      anastomosing cords embedded in a stroma which contained a significant component
      of alcian blue-positive myxoid substance forming a reticular pattern. These
      histopathological features gave an initial impression of a salivary gland-type
      carcinoma. On immunohistochemistry the tumor cells were strongly and diffusely
      positive for cytokeratins (AE1-3 and 5/6) and p63 and there was strong and
      diffuse nuclear positivity for Epstein-Barr virus-encoded small RNA on in situ
      hybridization. This case highlights the histomorphological variability of NK-NPC.
      Awareness of the histological spectrum of NK-NPC is important in clinical
      practice and this is not always adequately highlighted in currently used standard
      textbooks of Head and Neck Pathology. 

PMID- 24323540
TI  - Incorporation of 5-hydroxyindazole into the self-polymerization of dopamine for
      novel polymer synthesis.
AB  - Investigation into the mussel-inspired polymerization of dopamine has led to the
      realization that other compounds possessing potential quinone structures could
      undergo similar self-polymerizations in mild buffered aqueous conditions. To this
      end, 5-hydroxyindazole was added to a dopamine polymerization matrix in varying
      amounts, to study its incorporation into a polydopamine coating of silica
      particles. Solid-state (13) C NMR spectroscopy confirmed the presence of the
      indazole in the polymer shell when coated onto silica gel. SEM and DLS analysis
      also confirmed that the presence of the indazole in the reaction matrix yielded
      monodisperse polymer-coated particles, which retained their polymer shell upon HF
      etching, except when high levels of the indazole were used. Characterization data
      and examination of incorporation mechanism suggests that the 5-hydroxyindazole
      performs the function of a chain-terminating agent. Cytotoxicity studies of the
      polymer particles containing 5-hydroxyindazole showed dramatically lower toxicity
      levels compared to polydopamine alone. 

PMID- 24323541
TI  - Percutaneous edge-to-edge repair of the mitral valve in patients with
      degenerative versus functional mitral regurgitation.
AB  - OBJECTIVES: To prospectively assess the outcome of percutaneous edge-to-edge
      repair in patients with degenerative versus functional mitral regurgitation (MR).
      BACKGROUND: The optimal patient population eligible for percutaneous edge-to-edge
      repair has yet to be defined. METHODS: We analyzed 119 patients treated by
      percutaneous edge-to-edge repair for symptomatic MR, 72 patients with
      degenerative and 47 patients with functional MR. The primary endpoints were
      defined as procedural success (MR grade reduction >=1 grade) as well as a
      composite endpoint defined as freedom from MR 3+ or 4+, mitral valve
      reintervention and death 12 months after clip implantation. In patients with
      successful clip placement we further analyzed MR grade, New York Heart
      Association (NYHA) functional class, distance in the 6 min walking test and left
      ventricular volumes 12 months after clip implantation. RESULTS: The primary
      success rate of all intended clipping procedures was 83.3% for degenerative and
      89.4% for functional MR (P = 0.42). Regarding the composite endpoint we observed
      an event free survival of 59.7% in patients treated for degenerative MR and 63.8%
      in patients treated for functional MR (P = 0.73). We observed a highly
      significant reduction in MR grade as well as improvement in NYHA functional
      status in both groups 12 months after clip implantation. However, there was a
      more pronounced MR grade reduction in patients treated for degenerative MR
      compared with patients treated for functional MR. CONCLUSIONS: Percutaneous edge
      to-edge repair of the mitral valve is feasible and comparably effective in
      patients with degenerative and functional MR.

PMID- 24323543
TI  - Efficient and robust reforming catalyst in severe reaction conditions by
      nanoprecursor reduction in confined space.
AB  - The in situ autocombustion synthesis route is shown to be an easy and efficient
      way to produce nanoscaled nickel oxide containing lanthanum-doped mesoporous
      silica composite. Through this approach, ~3 nm NiO particles homogeneously
      dispersed in the pores of silica are obtained, while lanthanum is observed to
      cover the surface of the silica pore wall. Subsequent reduction of such composite
      precursors under hydrogen generates Ni(0) nanoparticles of a comparable size.
      Control over the size and size distribution of metallic nanoparticles clearly
      improved catalytic activity in the methane dry reforming reaction. In addition,
      these composite materials exhibit excellent stability under severe reaction
      conditions. This was achieved through the presence of LaOx species, which reduced
      active-site carbon poisoning, and the confinement effect of the mesoporous
      support, which reduced metallic particle sintering.

PMID- 24323544
TI  - Brief communication: Emergence chronology of permanent teeth in Nigerian
      children.
AB  - This study measured the mean age, duration, and sequence of the emergence of
      permanent dentition in Nigerian children and compared the findings with other
      population groups. The cross-sectional study involved 1,078 Nigerian children,
      aged 4-16 years old, from selected primary and secondary schools in the Ife
      Central local government area in Ile-Ife, Osun State. In general, compared to
      boys, girls had an earlier mean age of emergence of all the permanent teeth.
      Children from high socioeconomic class had an earlier mean age of emergence for
      the maxillary incisors (6.43 and 7.58 years) and mandibular incisors (5.28 and
      6.44 years) compared to children from middle and low socioeconomic classes,
      although socioeconomic effects were more mixed for premolars and molars. Compared
      to their counterparts in the USA, Australia, Belgium, and Iran, Nigerian children
      showed an earlier mean age of emergence of all the permanent teeth studied except
      for Pakistani boys, who had an earlier mean age of emergence of the maxillary
      premolars and second molar. Poorer economic status has been associated with
      delayed dental development; however, when compared to other populations, the
      Nigerian children in this study have earlier mean emergence ages than children
      from wealthier countries such as the USA and Australia.

PMID- 24323545
TI  - Different responses of soil respiration and its components to nitrogen addition
      among biomes: a meta-analysis.
AB  - Anthropogenic activities have increased nitrogen (N) deposition by threefold to
      fivefold over the last century, which may considerably affect soil respiration
      (Rs). Although numerous individual studies and a few meta-analyses have been
      conducted, it remains controversial as to how N addition affects Rs and its
      components [i.e., autotrophic (Ra) and heterotrophic respiration (Rh)]. To
      reconcile the difference, we conducted a comprehensive meta-analysis of 295
      published studies to examine the responses of Rs and its components to N addition
      in terrestrial ecosystems. We also assessed variations in their responses in
      relation to ecosystem types, environmental conditions, and experimental duration
      (DUR). Our results show that N addition significantly increased Rs by 2.0% across
      all biomes but decreased by 1.44% in forests and increased by 7.84% and 12.4% in
      grasslands and croplands, respectively (P < 0.05). The differences may largely
      result from diverse responses of Ra to N addition among biomes with more
      stimulation of Ra in croplands and grasslands compared with no significant change
      in forests. Rh exhibited a similar negative response to N addition among biomes
      except that in croplands, tropical and boreal forests. Methods of partitioning Rs
      did not induce significant differences in the responses of Ra or Rh to N
      addition, except that Ra from root exclusion and component integration methods
      exhibited the opposite responses in temperate forests. The response ratios (RR)
      of Rs to N addition were positively correlated with mean annual temperature
      (MAT), with being more significant when MAT was less than 15  degrees C, but
      negatively with DUR. In addition, the responses of Rs and its components to N
      addition largely resulted from the changes in root and microbial biomass and soil
      C content as indicated by correlation analysis. The response patterns of Rs to N
      addition as revealed in this study can be benchmarks for future modeling and
      experimental studies.

PMID- 24323546
TI  - Chemical proteomic strategies for the discovery and development of anticancer
      drugs.
AB  - Cancer is one of the leading causes of death globally. Drug discovery and
      development against cancer is thus among the most pursuing goals nowadays.
      Although the majority of anticancer drugs targeted on proteins, the
      identification and validation of drug targets and their regulated pathways remain
      a bottleneck in the drug R&D processes. Fortunately, chemical proteomic
      strategies based on the perfect combination of various targeted affinity
      chromatography and high-throughput MS analysis have emerged as a powerful tool
      for the large-scale identification of proteome-wide drug-protein interactions,
      and demonstrated great promise in elucidating complex underlying mechanisms of
      drug action against cancers. In this context, an updated overview of the chemical
      proteomic strategies, such as activity-based protein profiling (ABPP), compound
      centric chemical proteomics (CCCP), and other targeted affinity chromatographic
      approaches for modern anticancer drug discovery and development will be provided.
      Some most recent successful applications in this area will be highlighted. Future
      perspectives on this subject will also be discussed with a particular emphasis on
      small molecule natural products and their derivatives. 

PMID- 24323547
TI  - Abstracts of the UCD School of Medicine & Medical Science, Summer Student
      Research Awards 2013, 3rd October 2013, UCD, Dublin, Ireland.

PMID- 24323548
TI  - Abstracts of the Fifty Fourth Annual Meeting of the Irish
      Otorhinolaryngology/Head and Neck Society. October 10-11, 2013, Ireland.

PMID- 24323549
TI  - Evaluation of the effect of intra-operative intravenous fluid on post-operative
      pain and pulmonary function: a randomized trial comparing 10 and 30 ml kg(-1) of
      crystalloid.
AB  - BACKGROUND: Existing evidence suggests that administration of intravenous fluids
      has been shown to improve outcomes including pain in gynecological laparoscopic
      surgery but the optimum fluid dose has not been determined. AIMS: To determine
      the effect of administration of intravenous fluids on post-operative pain and
      pulmonary function after gynecological laparoscopy. METHODS: In a prospective
      randomized double-blinded study 100 ASA 1 and 2 elective patients undergoing
      gynecological laparoscopy were randomized to receive intravenous compound sodium
      lactate 10 ml kg(-1) (CSL10-restrictive) or 30 ml kg(-1) (CSL30-liberal)
      administered intra-operatively. The primary outcome measure was the post
      operative pain score at 24, 48 and 72 h, assessed by 0-10 verbal rating scale
      (VRS). Pulmonary function (FEV1, FVC, PEFR) and oxygen saturation were also
      measured. RESULTS: Patients who received CSL 30 had lower post-operative pain
      scores than CSL 10 (ANCOVA-mean difference = 0.47, 95 % CI 0.11-0.83, P = 0.01).
      Post-operative pain VRS was lower in CSL30 than CSL10 at 48 h (mean difference
      0.56, 95 % CI 0.04-1.09, P = 0.036). Patients in CSL30 reported shoulder tip pain
      less frequently than those in CSL10 (30.4 vs. 43.9 % of assessments, P = 0.03, OR
      0.58) but reported wound pain more frequently 39.0 vs. 24.2 %, P = 0.01, OR 2.0).
      Indices of pulmonary function did not differ between groups at any time.
      CONCLUSIONS: Liberal compared to restrictive administration of i.v. crystalloid
      is associated with a clinical modest reduction in pain. Pulmonary dysfunction was
      not increased with liberal fluid administration.

PMID- 24323550
TI  - A comparison of 3-D computed tomography versus 2-D radiography measurements of
      ulnar variance and ulnolunate distance during forearm rotation.
AB  - Positive ulnar variance is associated with ulnar impaction syndrome and ulnar
      variance is reported to increase with pronation. However, radiographic
      measurement can be affected markedly by the incident angle of the X-ray beam. We
      performed three-dimensional (3-D) computed tomography measurements of ulnar
      variance and ulnolunate distance during forearm rotation and compared these with
      plain radiographic measurements in 15 healthy wrists. From supination to
      pronation, ulnar variance increased in all cases on the radiographs; mean ulnar
      variance increased significantly and mean ulnolunate distance decreased
      significantly. However on 3-D imaging, ulna variance decreased in 12 cases on
      moving into pronation and increased in three cases; neither the mean ulnar
      variance nor mean ulnolunate distance changed significantly. Our results suggest
      that the forearm position in which ulnar variance increased varies among
      individuals. This may explain why some patients with ulnar impaction syndrome
      complain of wrist pain exacerbated by forearm supination. It also suggests that
      standard radiographic assessments of ulnar variance are unreliable. 

PMID- 24323551
TI  - Genetics studies in ischaemic stroke.
AB  - Conventional risk factors such as high blood pressure account for a significant
      proportion of stroke risk, but much stroke risk remains unexplained.
      Epidemiological evidence suggests genetic predisposition accounts for some of
      this unexplained risk. Many candidate genes association studies have been
      performed but have lead to largely disappointing results. The genome-wide
      association study (GWAS) approach allows novel associations to be identified with
      as many as one million polymorphisms (genetic variants) across the genome. It has
      been successfully applied to other complex diseases, including other
      cardiovascular diseases, but stroke has lagged behind. A number of GWAS projects
      in stroke are now underway. Genetic variants originally identified using the GWAS
      approach in atrial fibrillation and coronary artery disease have been shown to
      also confer an increased risk of stroke. These associations have been with
      specific subtypes of stroke, emphasising the importance of accurate stroke
      subtyping. The use of intermediate phenotypes for stroke, such as white matter
      hyperintensities on MRI and carotid intima-media thickness, is also discussed. 

PMID- 24323552
TI  - Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage
      pathophysiological background and clinical findings.
AB  - The time span from symptom onset to treatment initiation remains a critical
      variable determining the efficacy of thrombolysis in acute ischemic stroke. To
      date, performing a brain scan is indispensable prior to therapy in order to
      differentiate between patients with ischemic stroke and those with intracerebral
      hemorrhage (ICH). This causes substantial treatment delay, as thrombolysis cannot
      be applied prior to hospital admission at much earlier time points. Recently,
      brain-specific astroglial proteins (i.e., glial fibrillary acidic protein (GFAP),
      S100B) were identified to be released rapidly from the cytoplasm of destroyed
      cells in case of acute ICH. Elevated serum concentrations were found within the
      first 6 h after ICH onset. In contrast, in ischemic stroke, these proteins are
      released with delay, mirroring the more gradual occurrence of necrotic cell death
      and blood brain barrier disruption. S100B and GFAP may qualify as candidate serum
      biomarkers which are able to differentiate between ischemic stroke and ICH in the
      emergency phase of stroke. This minireview enlightens the pathophysiological
      background of this finding and provides an overview on currently available
      clinical data. 

PMID- 24323553
TI  - Reperfusion therapy for acute stroke improves outcome by decreasing
      neuroinflammation.
AB  - Inflammation is a major step in the ischemic cascade, and proinflammatory
      cytokines, adhesion molecules and chemokines have been related to brain injury
      after stroke. To investigate if tissue plasminogen activator (tPA) treatment
      decreases the deleterious neuroinflammatory response that follows ischemic
      stroke. Our target population was 80 patients with ischemic stroke involving the
      middle cerebral artery (MCA) territory. Among them, 41 received tPA within 3 h of
      symptom onset according to National Institute of Neurological Disorders and
      Stroke recommendations and the remaining 39 were assessed prior to local approval
      of tPA. In all patients, blood samples were obtained at 12 and 24 h after symptom
      onset. Serum determinations of interleukin (IL)-6, inter-cellular adhesion
      molecule 1 (ICAM-1), IL-8 and tumor necrosis factor-alpha (TNF-alpha) were
      obtained by ELISA. National Institutes of Health Stroke Scale (NIHSS) and
      transcranial Doppler recordings (proximal/distal occlusion, p.o/d.o) were
      obtained at baseline and follow-up. No differences were found between the two
      groups in baseline NIHSS scores (tPA = 17 and control = 17; p = 0.38) or MCA
      status (tPA: p.o = 65.8%, control: p.o = 55.3%; p = 0.41). We found a lower level
      of mean IL-6 and IL-8 in the tPA treatment group: IL-6 (14.06 vs. 37.88 pg/ml, p
      = 0.001) and IL-8 (70.98 vs. 465 pg/ml, p < 0.001). No significant changes
      appeared for ICAM-1 and TNF-alpha. This biological response was accompanied by a
      neurological improvement (24 h NIHSS: tPA = 11 and control = 15; p = 0.024) and a
      mortality reduction (tPA = 9.75% vs. controls = 28.2%; p = 0.038). Patients who
      improved and those who recanalised had the lowest IL-6 levels (p < 0.005). tPA
      treatment reduces the severity of the inflammatory phenomena that follows stroke.
      These results may partially explain the efficacy of reperfusion therapy on stroke
      outcome. 

PMID- 24323554
TI  - Proteomic identification of novel plasma kallikrein substrates in the astrocyte
      secretome.
AB  - Plasma kallikrein (PK) is activated during hemorrhage and has been implicated in
      cerebral vascular permeability and edema. To further characterize the potential
      effects of PK on the brain that may follow cerebral vascular injury, we have
      utilized a proteomics approach to search for novel PK substrates in the astrocyte
      secretome. Extracellular proteins released by astrocytes are critical mediators
      of cerebral homeostasis, including roles in synapse function and vascular
      integrity. We identified 1,108 proteins in astrocyte condition medium and 295 of
      these were annotated as secreted proteins. The total abundance of nine proteins
      was changed after treatment with PK. Characterization of the secreted proteins
      revealed low molecular weight fragments for 59 proteins in conditioned media
      exposed to PK that were not observed in untreated controls. The most striking
      finding from this study was the appearance of fragmentation of 26 extracellular
      matrix-associated proteins including collagen isoforms 1-6 and11, nidogen-1 and 
      2, lysyl oxidase-like protein 1, and matrix metalloproteinase 19 in the presence
      of PK. We also demonstrated that PK induced the fragmentation of non-matrix
      proteins, including apolipoprotein E. This report further characterizes the
      astrocyte secretome and identifies novel potential targets of PK-induced
      proteolysis that may contribute to its effects on the brain following vascular
      injury. 

PMID- 24323555
TI  - MicroRNAs in Cerebral Ischemia.
AB  - Pathogenesis of cerebral ischemia has so far been described in the context of
      proteins and the pathways that they regulate. The discovery of biomarkers has
      also been focussed mainly on proteins and to some extent on the mRNAs that encode
      them. The knowledge on the role of microRNAs in understanding the pathogenesis of
      cerebral ischemia is still at its infancy. In this study, using rat models
      subjected to middle cerebral artery occlusion, we have profiled the microRNAs at
      different reperfusion times (0 to 48 h) to understand the progression of cerebral
      ischemia. We have also attempted to correlate the expression of microRNAs to
      treatment with an NMDA antagonist (MK801) and to protein expression with the hope
      of demonstrating the potential use of microRNAs as early biomarkers of stroke. 

PMID- 24323556
TI  - Assessing the quality and reproducibility of a proteomic platform for clinical
      stroke biomarker discovery.
AB  - The aim of this study was to investigate the quality and reproducibility of mass
      spectra derived from a matrix-assisted laser desorption ionisation time-of-flight
      mass spectrometry (MALDI-TOF MS) platform in a patient population undergoing
      carotid endarterectomy. Plasma samples were either digested with trypsin or left
      undigested, fractionated with either C18 or weak cation exchange (WCX) columns
      and analysed by MALDI-TOF MS. Quality of mass spectra for each method was
      assessed by baseline correction (lower area under the curve ratio indicating
      higher quality) and signal-to-noise ratio. Mean coefficient of variation (CV%)
      assessed reproducibility between repeated experiments and methods. Identified
      mass peak intensity differences were assessed for consistency across repeated
      experiments. Plasma from six patients was analysed. The quality of mass spectra
      was significantly better when derived from digested plasma fractionated by either
      WCX or C18 methods compared to undigested plasma fractionated by WCX (analysis of
      variance, p < 0.05). Mean CV% for repeated experiments was 18% and 28% for WCX
      and C18 fractionated digested plasma, respectively. A small number of differences
      in mass peak intensities were consistently observed in repeated experiments.
      Repeated experiments are required to confidently identify non-random mass peak
      intensity differences as putative plasma biomarkers that merit further
      investigation. 

PMID- 24323557
TI  - In vitro investigation of skin damage due to microscale shearing.
AB  - Despite several studies dealing with the mechanical and tribological properties
      of skin, the majority of these investigations have been performed at macroscopic
      levels. However, because of the multilayer structure of skin, it is necessary to
      perform studies at microscopic scales to reveal the effect of individual layer
      constituents on the overall skin response to mechanical stimuli. To bridge the
      gap in knowledge of the micromechanical behavior of skin, a custom-made
      mechanical tester, optical microscopy, and cross-sectional histology were used to
      examine the deformation and tribological behavior of porcine skin subjected to
      various normal and shear loadings. Representative friction and wear results of
      skin tested under unidirectional and reciprocating (cyclic) shearing (scratching)
      conditions are interpreted in terms of the scratching speed, normal load, and
      number of scratch cycles to illustrate the effects of stratum corneum, cellular
      epidermis, and dermis on the friction and wear characteristics of skin. Depending
      on the normal load and scratch time (cycles), different friction mechanisms
      (i.e., adhesion, plowing, and squeeze-film lubrication) and wear mechanisms
      (i.e., surface plasticity/plowing, bulk shearing, cohesive failure, tearing, and
      delamination) were found to control shear-induced skin damage. The results of
      this study provide insight into microscale friction and wear processes
      influencing the mechanical response of skin subjected to normal and shear surface
      tractions.

PMID- 24323558
TI  - [Medical care for allergic disorders in Germany: a paradox].
AB  - Medical care for allergic patients in Germany is decreasing, although the
      prevalence of allergic disorders continues to rise. This article describes the
      magnitude and the causes of this paradox. In addition, the consequences of this
      phenomenon for respiratory medicine and for the diagnosis and therapy of asthma
      are discussed. 

PMID- 24323559
TI  - [DGP-Newsletter December, 2013].

PMID- 24323560
TI  - Physician communication in a lung cancer center--does the message come across?
AB  - OBJECTIVE: Lung cancer patients require information about their diagnosis,
      treatment procedure and the treatment goal. We have examined recall of patients
      and how satisfied they were with physician communication. PATIENTS AND METHODS:
      101 patients with newly diagnosed lung cancer were interviewed shortly after the
      disclosure of diagnosis about their diagnosis, treatment procedure and treatment
      goal. Disclosing physicians were asked what information they had given. Physician
      information and patient recall was then compared. RESULTS: Eighty-six percent (86
      of 100 patients) knew their diagnosis, 81% recalled the treatment procedure
      correctly, and 42% knew if the treatment goal was curative or palliative. We
      found high satisfaction about communication of diagnosis and treatment procedure
      (83% resp.77%). However, satisfaction with communication of the treatment goal
      was 53% (51 of 97 patients) and significantly lower than satisfaction with
      communication of diagnosis and of treatment procedure. Patients who were informed
      by male physicians were significantly more satisfied with the disclosure about
      the treatment goal. CONCLUSIONS: Treatment goals are difficult to convey by
      untrained physicians. Further research is needed to understand how we can improve
      patients' understanding of and satisfaction with information about the treatment
      goal and prognosis and how physicians can improve their communication skills.

PMID- 24323561
TI  - Lifestyle engagement affects cognitive status differences and trajectories on
      executive functions in older adults.
AB  - The authors first examined the concurrent moderating role of lifestyle engagement
      on the relation between cognitive status (cognitively elite, cognitively normal
      [CN], and cognitively impaired [CI]) and executive functioning (EF) in older
      adults. Second, the authors examined whether baseline participation in lifestyle
      activities predicted differential 4.5-year stabilities and transitions in
      cognitive status. Participants (initial N = 501; 53-90 years) were from the
      Victoria Longitudinal Study. EF was represented by a 1-factor structure.
      Lifestyle activities were measured in multiple domains of engagement (e.g.,
      cognitive, physical, and social). Two-wave status stability groups included
      sustained normal aging, transitional early impairment, and chronic impairment.
      Hierarchical regressions showed that baseline participation in social activities
      moderated cognitive status differences in EF. CI adults with high (but not low)
      social engagement performed equivalently to CN adults on EF. Longitudinally,
      logistic regressions showed that engagement in physical activities was a
      significant predictor of stability of cognitive status. CI adults who were more
      engaged in physical activities were more likely to improve in their cognitive
      status over time than their more sedentary peers. Participation in cognitive
      activities was a significant predictor of maintenance in a higher cognitive
      status group. Given that lifestyle engagement plays a detectable role in healthy,
      normal, and impaired neuropsychological aging, further research in activity
      related associations and interventions is recommended. 

PMID- 24323562
TI  - p21 overexpression sensitizes osteosarcoma U2OS cells to cisplatin via evoking
      caspase-3 and Bax/Bcl-2 cascade.
AB  - Osteosarcoma is the most common form of primary malignant bone tumor that mainly
      occurs in juvenile patients. The mechanisms of formation and development of
      osteosarcoma have been studied for a long time. Recently, more and more evidence
      showed that p21 plays important roles in regulating tumor growth. To study the
      effects of p21 on the chemosensitivity of human osteosarcoma U2OS cells to
      cisplatin and its relevant mechanisms, we stably transfect the pC-21-SN3 vector
      containing P21 to U2O3 cells (U2O3-p21), which was identified by RT-PCR and
      Western blot. The results showed that no p21 was expressed in U2OS and U2OS-vec
      cells, but it was highly expressed in U2O3-p21 cells at mRNA and protein levels.
      The growth of U2OS cells was almost not influenced by p21 alone. However, U2O3
      p21 cells underwent more obvious apoptotic morphological changes than U2OS and
      U2OS-vec cells after being treated with cisplatin (5 MUg) for 72 h. Besides,
      increased expression of cleaved caspase-3 and Bax/Bcl-2 ratio was observed in
      cisplatin-treated U2O3-p21 cells. These data clearly indicated that exogenous p21
      gene transfection could enhance the cisplatin-induced cytotoxicity against human
      osteosarcoma U2OS cells, at least in part, by activating caspase-3 cascade and
      increasing Bax/Bcl-2 ratio.

PMID- 24323564
TI  - Differential association of RANTES-403 and IL-1B-1464 polymorphisms on
      histological subtypes in male Korean patients with gastric cancer.
AB  - The aims of this study were to elucidate the association between RANTES-403 and
      an increased risk of gastric cancer in Korean males and to investigate the gene
      gene interaction between IL-1B and RANTES. In total, 218 male patients with
      gastric cancer (114 diffuse types, 97 intestinal types, and 7 mixed types) and
      377 male controls were included. RANTES-403 was genotyped, and age-adjusted odds
      ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic
      regression. A multifactor dimensionality reduction (MDR) test with three-way
      split interval validation confirmed by likelihood ratio and permutation analysis
      was carried out. A significant increase in the risk of gastric cancer for the
      intestinal-type group was observed for IL-1B-1464G carriers (OR = 2.535; 95% CI =
      1.121-5.732; P = 0.02) as well as for those with IL-1B-1464 CG (OR = 2.342; 95%
      CI = 0.998-5.500; P = 0.05) or IL-1B-1464 GG (OR = 2.819; 95% CI = 1.170-6.793; P
      = 0.02). For the RANTES-403 genotype, there was no significant difference in the
      risk of gastric cancer between the overall gastric cancer and the control groups.
      When further stratified according to histological types, RANTES-403A carriers (OR
      = 1.743; 95% CI = 1.086-2.798; P = 0.021) or heterozygotes (OR = 1.791; 95% CI =
      1.092-2.935; P = 0.021) showed increased risk for developing diffuse-type gastric
      cancer. MDR revealed a three-way locus-locus interaction between RANTES-403AA, IL
      1B-1464GG, and IL-1B-511CT for diffuse-type gastric cancer in Korean males. We
      demonstrated that RANTES-403 was significantly associated with the risk of
      developing diffuse-type gastric cancer in men and found a possible gene-gene
      interaction between RANTES and IL-1B polymorphisms in gastric cancer
      carcinogenesis.

PMID- 24323565
TI  - Malignant melanoma in early-treated Parkinson's disease: the NET-PD trial.
AB  - BACKGROUND: The risk for malignant melanoma is higher than expected in
      Parkinson's disease (PD). The National Institutes of Health (NIH) Exploratory
      Trials in PD (NET-PD) Long-term Study 1 (LS-1) trial is a contemporary phase 3
      study of subjects with early, treated PD. The objective of this work was to
      assess the incidence of malignant melanoma in a PD cohort. METHODS: Incident
      melanoma cases were identified from the adverse events log. The expected number
      of cases was calculated, using the expected incidence rates and the number of
      person-years. RESULTS: A total of 618 females and 1119 males were followed for
      6452 person-years; 19 new melanoma cases were observed. The expected number was
      5.29. The standardized event ratio compared to the general population was 3.6
      (95% confidence interval, 2.2-5.6). CONCLUSIONS: The risk for developing melanoma
      was higher than expected in the NET-PD LS-1 cohort and was similar to the risk
      reported in earlier comparable clinical trial cohorts. Dermatologic screening may
      be useful in Parkinson's disease to identify melanoma at an early stage.

PMID- 24323563
TI  - The microRNA networks of TGFbeta signaling in cancer.
AB  - In metazoans, the transforming growth factor beta (TGFbeta) signaling regulates a
      host of activities ranging from embryonic development to tissue homeostasis. The
      normal as well as tumor cells respond to this cytokine signaling pathway in a
      highly context-dependent manner. It acts as a potent tumor suppressor initially
      by inducing cell cycle arrest and apoptosis. But advanced tumors often misuse
      TGFbeta signaling for tumor progression by selectively disabling the tumor
      suppressor arm and using other properties of TGFbeta signaling such as induction
      of angiogenesis, epithelial to mesenchymal transition, and metastases. This dual
      role of TGFbeta in cancer remained a mystery until recently. But recent advances
      in the field of microRNA provided a deeper understanding about this dual nature
      of TGFbeta signaling in cancers. In the present review, we present an account of
      the role of microRNAs in deregulating TGFbeta signaling and modulating cancer
      cell behavior during tumor initiation and cancer progression. This review also
      includes a discussion on the recent advances in the deregulation of TGFbeta
      signaling in carcinogenesis. 

PMID- 24323566
TI  - Severe mitral regurgitation requiring ECMO therapy treated by interventional
      valve reconstruction using the MitraClip.
AB  - Surgical repair is considered the gold standard in severe mitral valve
      regurgitation. Multi-organ failure because of acute mitral insufficiency,
      however, can be challenging to manage as it aggravates to an inoperable state. We
      report the case of a 59 year old woman who presented with pulmonary oedema
      because of high grade mitral regurgitation. A recompensation prior to surgery
      using medical therapy failed and the patient developed a progressive multi-organ
      failure including pulmonary, circulatory, and renal failure within days.
      Symptomatically, our patient could be stabilized employing an extracorporeal
      membrane oxygenation and an intra-aortic balloon pump. A surgical mitral valve
      repair was ruled out because of the multi-organ failure. We performed an
      interventional valve reconstruction using the MitraClip device continuing the
      extracorporeal membrane oxygenation and the intra-aortic balloon counterpulsation
      therapy during the procedure. After clipping, multi-organ failure regressed and
      the extracorporeal membrane oxygenation could be explanted at day two after
      intervention. (c) 2013 Wiley Periodicals, Inc.

PMID- 24323567
TI  - Use of empirical likelihood to calibrate auxiliary information in partly linear
      monotone regression models.
AB  - In statistical analysis, a regression model is needed if one is interested in
      finding the relationship between a response variable and covariates. When the
      response depends on the covariate, then it may also depend on the function of
      this covariate. If one has no knowledge of this functional form but expect for
      monotonic increasing or decreasing, then the isotonic regression model is
      preferable. Estimation of parameters for isotonic regression models is based on
      the pool-adjacent-violators algorithm (PAVA), where the monotonicity constraints
      are built in. With missing data, people often employ the augmented estimating
      method to improve estimation efficiency by incorporating auxiliary information
      through a working regression model. However, under the framework of the isotonic
      regression model, the PAVA does not work as the monotonicity constraints are
      violated. In this paper, we develop an empirical likelihood-based method for
      isotonic regression model to incorporate the auxiliary information. Because the
      monotonicity constraints still hold, the PAVA can be used for parameter
      estimation. Simulation studies demonstrate that the proposed method can yield
      more efficient estimates, and in some situations, the efficiency improvement is
      substantial. We apply this method to a dementia study.

PMID- 24323568
TI  - Baseline prostate inflammation is associated with a reduced risk of prostate
      cancer in men undergoing repeat prostate biopsy: results from the REDUCE study.
AB  - BACKGROUND: The current study was performed to evaluate whether baseline acute
      and chronic prostate inflammation among men with an initial negative biopsy for
      prostate cancer (PCa) increased the risk of subsequent PCa detection in a
      clinical trial with systematic biopsies. METHODS: A retrospective analysis was
      performed of 6238 men aged 50 years to 75 years with prostate-specific antigen
      levels between 2.5 ng/mL and 10 ng/mL and a prior negative biopsy in the
      REduction by DUtasteride of PCa Events study who completed a 2-year biopsy. PCa,
      acute prostate inflammation, and chronic prostate inflammation were assessed by
      central review. The association between inflammation in baseline prostate
      biopsies and positive 2-year and 4-year repeat biopsies was evaluated with the
      chi-square test and logistic regression analysis adjusting for baseline
      covariates. RESULTS: Acute and chronic inflammation and both were detected in 46
      baseline biopsies (1%), 3931 baseline biopsies (63%), and 892 baseline biopsies
      (14%), respectively. Acute and chronic inflammation were found to be
      significantly associated with each other (P<.001). Acute inflammation at baseline
      biopsy was associated with younger age, lower prostate-specific antigen levels,
      and a smaller prostate (all P<.01), whereas chronic inflammation was associated
      with older age and larger prostate glands (all P<0.01). At the 2-year biopsy, the
      prevalence of PCa was 14% (N=900 patients). On univariable and multivariable
      analysis, both acute and chronic inflammation were found to be significantly
      associated with a lower PCa risk (acute univariable: odds ratio [OR], 0.65
      [P<.001] and multivariable: OR, 0.75 [P=.012] and chronic univariable: OR, 0.61
      [P<.001] and multivariable: OR, 0.65 [P<.001]). At the time of 4-year biopsy,
      only acute inflammation was found to be associated with a lower PCa risk.
      CONCLUSIONS: Baseline acute and chronic inflammation were both found to be
      independently associated with a lower PCa risk. From a clinical standpoint,
      inflammation in negative biopsies for PCa may lower the risk of subsequent PCa
      detection.

PMID- 24323569
TI  - Individual and combined effects of multiple high-risk triggers on postcessation
      smoking urge and lapse.
AB  - INTRODUCTION: Negative affect, alcohol consumption, and presence of others
      smoking have consistently been implicated as risk factors for smoking lapse and
      relapse. What is not known, however, is how these factors work together to affect
      smoking outcomes. This paper uses ecological momentary assessment (EMA) collected
      during the first 7 days of a smoking cessation attempt to test the individual and
      combined effects of high-risk triggers on smoking urge and lapse. METHODS:
      Participants were 300 female smokers who enrolled in a study that tested an
      individually tailored smoking cessation treatment. Participants completed EMA,
      which recorded negative affect, alcohol consumption, presence of others smoking,
      smoking urge, and smoking lapse, for 7 days starting on their quit date. RESULTS:
      Alcohol consumption, presence of others smoking, and negative affect were,
      independently and in combination, associated with increase in smoking urge and
      lapse. The results also found that the relationship between presence of others
      smoking and lapse and the relationship between negative affect and lapse were
      moderated by smoking urge. CONCLUSIONS: The current study found significant
      individual effects of alcohol consumption, presence of other smoking, and
      negative affect on smoking urge and lapse. Combing the triggers increased smoking
      urge and the risk for lapse to varying degrees, and the presence of all 3
      triggers resulted in the highest urge and lapse risk.

PMID- 24323570
TI  - Digital detection for tobacco control: online reactions to the 2009 U.S.
      cigarette excise tax increase.
AB  - INTRODUCTION: The Internet is revolutionizing tobacco control, but few have
      harnessed the Web for surveillance. We demonstrate for the first time an approach
      for analyzing aggregate Internet search queries that captures precise changes in
      population considerations about tobacco. METHODS: We compared tobacco-related
      Google queries originating in the United States during the week of the State
      Children's Health Insurance Program (SCHIP) 2009 cigarette excise tax increase
      with a historic baseline. Specific queries were then ranked according to their
      relative increases while also considering approximations of changes in absolute
      search volume. RESULTS: Individual queries with the largest relative increases
      the week of the SCHIP tax were "cigarettes Indian reservations" 640% (95% CI, 472
      918), "free cigarettes online" 557% (95% CI, 432-756), and "Indian reservations
      cigarettes" 542% (95% CI, 414-733), amounting to about 7,500 excess searches. By
      themes, the largest relative increases were tribal cigarettes 246% (95% CI, 228
      265), "free" cigarettes 215% (95% CI, 191-242), and cigarette stores 176% (95%
      CI, 160-193), accounting for 21,000, 27,000, and 90,000 excess queries. All
      avoidance queries, including those aforementioned themes, relatively increased
      150% (95% CI, 144-155) or 550,000 from their baseline. All cessation queries
      increased 46% (95% CI, 44-48), or 175,000, around SCHIP; including themes for
      "cold turkey" 19% (95% CI, 11-27) or 2,600, cessation products 47% (95% CI, 44
      50) or 78,000, and dubious cessation approaches (e.g., hypnosis) 40% (95% CI, 33
      47) or 2,300. CONCLUSIONS: The SCHIP tax motivated specific changes in population
      considerations. Our strategy can support evaluations that temporally link tobacco
      control measures with instantaneous population reactions, as well as serve as a
      springboard for traditional studies, for example, including survey questionnaire
      design.

PMID- 24323571
TI  - Conceptualizing analyses of ecological momentary assessment data.
AB  - Ecological momentary assessment (EMA) methods, which involve collection of real
      time data in subjects' real-world environments, are particularly well suited to
      studying tobacco use. Analyzing EMA datasets can be challenging, as the datasets
      include a large and varied number of observations per subject and are relatively
      unstructured. This paper suggests that time is typically a key organizing
      principle in EMA data and that conceptualizing the data as a timeline of events,
      behaviors, and experiences can help define analytic approaches. EMA datasets lend
      themselves to answering a diverse array of research questions, and the research
      question must drive how data are arranged for analysis, and the kinds of
      statistical models that are applied. This is illustrated this with brief examples
      of diverse analyses applied to answer different questions from an EMA study of
      tobacco use and relapse. 

PMID- 24323572
TI  - Changes in effectiveness of cigarette health warnings over time in Canada and the
      United States, 2002-2011.
AB  - INTRODUCTION: Article 11 of the World Health Organization's Framework Convention
      on Tobacco Control (FCTC) requires countries to implement health warnings on
      tobacco products. The Article 11 guidelines advise countries to periodically
      rotate warnings to prevent "wearout" of the health warnings. This study
      investigates potential wearout of cigarette health warnings during a period of 9
      years in 2 countries: Canada, where larger pictorial warnings were implemented
      approximately 1 year prior to the study, and in the United States, where small
      text-only warnings were in place for 17 years at the beginning of the study.
      METHODS: Data were drawn from national samples of smokers from the International
      Tobacco Control (ITC) Surveys in Canada (N = 5,309), and the United States (N =
      6,412) who were originally recruited by telephone with random digit dialing.
      Changes in 4 measures of health warning effectiveness and in a composite Labels
      Impact Index were examined over 8 waves of survey data (2002-2011). Analyses were
      conducted in 2012. RESULTS: The health warning effectiveness measures and the
      Labels Impact Index indicated that the effectiveness of both the Canadian, and
      the U.S. warnings declined significantly over time. The Canadian warnings showed
      greater declines in effectiveness than the U.S. warnings, likely due to the
      initial novelty of the Canadian warnings. Despite the greater decline in Canada,
      the Canadian pictorial warnings were significantly more effective than the U.S.
      text-only warnings throughout the study. CONCLUSIONS: Health warnings decline in
      effectiveness over time. Health warnings on tobacco products should be changed
      periodically to maintain effectiveness.

PMID- 24323573
TI  - Sociodemographic correlates of exclusive and concurrent use of smokeless and
      smoked tobacco products among Nigerian men.
AB  - INTRODUCTION: This study sought to determine the sociodemographic correlates of
      exclusive and concurrent use of smokeless tobacco (SLT) and smoking (i.e., dual
      use) and to explore the association between SLT use and the amount of cigarettes
      smoked per day. METHODS: Data were obtained from a nationally representative
      sample of Nigerian men aged 15-59 years (N = 15,453) who participated in the 2008
      Nigerian Demographic and Health Survey (NDHS). The NDHS used an interviewer
      administered questionnaire to collect data on participants' sociodemographic
      characteristics and tobacco use status. Taking account of the multistage sampling
      used in the NDHS, data analyses included descriptive statistics, chi-square
      analysis, and multivariable adjusted multinomial logistic regression analysis.
      RESULTS: Of the respondents, 12.2% (n = 1,842) were tobacco users, out of which
      24.5% (n = 477) were exclusive SLT users, 69% (n = 1,236) were exclusive smokers,
      and 6.5% (n = 129) were dual users. Both SLT use and smoking were most prevalent
      among the Igbo ethnic group and among the least educated men. SLT use was most
      prevalent among those in the southeast (9.75%) and north-central (7.71%) regions,
      where smoking was also common. The number of cigarettes smoked per day was not
      significantly different among dual users when compared with exclusive smokers
      (7.3 vs. 5.6; p = .088). Dual users were also more likely to self-identify as
      traditionalists (RRR = 6.03; 95% CI = 2.96-12.28) compared with self-identifying
      as practicing Islam or Christianity. CONCLUSIONS: There are distinctive ethnic
      and regional differences in tobacco use patterns among Nigerian men, and SLT use
      was not associated with reduced smoking intensity among dual users.

PMID- 24323574
TI  - Knowledge, attitudes, and normative beliefs as predictors of hookah smoking
      initiation: a longitudinal study of university students.
AB  - INTRODUCTION: While cross-sectional studies have shown that hookah tobacco
      smoking (HTS) is an increasingly popular behavior among university students,
      little is known about factors associated with initiation. This study sought to
      determine associations between knowledge, attitudes, and normative beliefs and
      initiation of HTS among university students. METHODS: Data were from a
      prospective longitudinal cohort study of 569 randomly selected first- and second
      year university students. Online questionnaires that were developed in accordance
      with our composite theoretical model were completed in September 2010 and April
      2011. RESULTS: About one-seventh (13%) of participants initiated HTS by follow
      up. Positive attitudes and favorable normative beliefs were associated with
      increased adjusted odds of initiation (AOR = 4.12, 95% CI = 2.56, 6.59; and AOR =
      2.01, 95% CI = 1.35, 2.99, respectively), while negative attitudes were
      associated with decreased adjusted odds (AOR = 0.62, 95% CI = 0.48, 0.80).
      Correct knowledge regarding toxicants associated with HTS was not significantly
      associated with initiation. CONCLUSIONS: While positive attitudes and favorable
      normative beliefs are associated with initiation of HTS in a cohort of never
      users, increased knowledge about toxins is not associated with lower initiation.
      It may be particularly valuable for educational interventions to attempt to alter
      positive attitudes and normative beliefs related to HTS.

PMID- 24323575
TI  - Redox-triggered self-rolling robust hydrogel tubes for cell encapsulation.
AB  - In this study, mechanically strong hydrogels are synthesized by
      photopolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine, poly(ethylene glycol)
      methacrylate, and disulfide-containing cross-linker, N'N-bis(acryloyl)cystamine.
      The bilayer hydrogel with distinct cross-linking density is shown to self-roll
      into a 3D tube, which could still be well reinforced by hydrogen bondings, upon
      exposing reductants such as 1,4-dithio-DL-threitol (DTT) or L-glutathione (GSH),
      because the redox-induced cleavage of disulfide bonds results in the imbalanced
      internal shrinking stress between two layers. At an intracellular level of GSH,
      model L929 cells-seeded bilayer gel sheet could curl up into a 3D tubular
      scaffold where the cells maintained good viability. 

PMID- 24323576
TI  - Engineering the TiO2 -graphene interface to enhance photocatalytic H2 production.
AB  - In this work, TiO2 -graphene nanocomposites are synthesized with tunable TiO2
      crystal facets ({100}, {101}, and {001} facets) through an anion-assisted method.
      These three TiO2 -graphene nanocomposites have similar particle sizes and surface
      areas; the only difference between them is the crystal facet exposed in TiO2
      nanocrystals. UV/Vis spectra show that band structures of TiO2 nanocrystals and
      TiO2 -graphene nanocomposites are dependent on the crystal facets. Time-resolved
      photoluminescence spectra suggest that the charge-transfer rate between {100}
      facets and graphene is approximately 1.4 times of that between {001} facets and
      graphene. Photoelectrochemical measurements also confirm that the charge
      separation efficiency between TiO2 and graphene is greatly dependent on the
      crystal facets. X-ray photoelectron spectroscopy reveals that Ti-C bonds are
      formed between {100} facets and graphene, while {101} facets and {001} facets are
      connected with graphene mainly through Ti-O-C bonds. With Ti-C bonds between TiO2
      and graphene, TiO2 -100-G shows the fastest charge-transfer rate, leading to
      higher activity in photocatalytic H2 production from methanol solution. TiO2 -101
      G with more reductive electrons and medium interfacial charge-transfer rate also
      shows good H2 evolution rate. As a result of its disadvantageous electronic
      structure and interfacial connections, TiO2 -001-G shows the lowest H2 evolution
      rate. These results suggest that engineering the structures of the TiO2 -graphene
      interface can be an effective strategy to achieve excellent photocatalytic
      performances.

PMID- 24323577
TI  - Linking climate change projections for an Alaskan watershed to future coho salmon
      production.
AB  - Climate change is predicted to dramatically change hydrologic processes across
      Alaska, but estimates of how these impacts will influence specific watersheds and
      aquatic species are lacking. Here, we linked climate, hydrology, and habitat
      models within a coho salmon (Oncorhynchus kisutch) population model to assess how
      projected climate change could affect survival at each freshwater life stage and,
      in turn, production of coho salmon smolts in three subwatersheds of the Chuitna
      (Chuit) River watershed, Alaska. Based on future climate scenarios and
      projections from a three-dimensional hydrology model, we simulated coho smolt
      production over a 20-year span at the end of the century (2080-2100). The
      direction (i.e., positive vs. negative) and magnitude of changes in smolt
      production varied substantially by climate scenario and subwatershed. Projected
      smolt production decreased in all three subwatersheds under the minimum air
      temperature and maximum precipitation scenario due to elevated peak flows and a
      resulting 98% reduction in egg-to-fry survival. In contrast, the maximum air
      temperature and minimum precipitation scenario led to an increase in smolt
      production in all three subwatersheds through an increase in fry survival. Other
      climate change scenarios led to mixed responses, with projected smolt production
      increasing and decreasing in different subwatersheds. Our analysis highlights the
      complexity inherent in predicting climate-change-related impacts to salmon
      populations and demonstrates that population effects may depend on interactions
      between the relative magnitude of hydrologic and thermal changes and their
      interactions with features of the local habitat. 

PMID- 24323578
TI  - Demethylation of the human eotaxin-3 gene promoter leads to the elevated
      expression of eotaxin-3.
AB  - DNA demethylation has been primarily studied in the context of development
      biology, cell fate, and cancer, with less attention on inflammation. In this
      article, we investigate the association between DNA methylation and production of
      the chemoattractant cytokine eotaxin-3 in the tissue of patients with allergic
      disease. Regions of the human eotaxin-3 promoter were found to be hypomethylated
      in primary epithelial cells obtained from allergic tissue compared with normal
      control tissue. The demethylation of a specific CpG site (designated CpG 2),
      which is juxtaposed to a key cAMP-responsive element site, was significantly
      demethylated in patient-derived compared with normal control tissue-derived
      epithelial cells. Levels of methylation at CpG 2 inversely correlated with basal
      and IL-13-induced eotaxin-3 gene expression. Conversely, global inhibition of
      methylation with 5-azacytidine promoted eotaxin-3 production in association with
      decreasing CpG 2 methylation. In addition, the basal and IL-13-induced eotaxin-3
      transcriptional activity was suppressed by promoter methylation using a
      methylation-free in vitro system. Furthermore, EMSAs demonstrated that the
      attachment of CREB binding protein and activating transcription factor 2 (ATF-2)
      to the cAMP-responsive element site was methylation dependent. Taken together,
      these data identify a contributory role for DNA methylation in regulating eotaxin
      3 production in human allergic inflammation. 

PMID- 24323579
TI  - Munc18-2 and syntaxin 3 control distinct essential steps in mast cell
      degranulation.
AB  - Mast cell degranulation requires N-ethylmaleimide-sensitive factor attachment
      protein receptors (SNARE) and mammalian uncoordinated18 (Munc18) fusion accessory
      proteins for membrane fusion. However, it is still unknown how their interaction
      supports fusion. In this study, we found that small interfering RNA-mediated
      silencing of the isoform Munc18-2 in mast cells inhibits cytoplasmic secretory
      granule (SG) release but not CCL2 chemokine secretion. Silencing of its SNARE
      binding partner syntaxin 3 (STX3) also markedly inhibited degranulation, whereas
      combined knockdown produced an additive inhibitory effect. Strikingly, while
      Munc18-2 silencing impaired SG translocation, silencing of STX3 inhibited fusion,
      demonstrating unique roles of each protein. Immunogold studies showed that both
      Munc18-2 and STX3 are located on the granule surface, but also within the granule
      matrix and in small nocodazole-sensitive clusters of the cytoskeletal meshwork
      surrounding SG. After stimulation, clusters containing both effectors were
      detected at fusion sites. In resting cells, Munc18-2, but not STX3, interacted
      with tubulin. This interaction was sensitive to nocodazole treatment and
      decreased after stimulation. Our results indicate that Munc18-2 dynamically
      couples the membrane fusion machinery to the microtubule cytoskeleton and
      demonstrate that Munc18-2 and STX3 perform distinct, but complementary, functions
      to support, respectively, SG translocation and membrane fusion in mast cells. 

PMID- 24323581
TI  - Insulin inhibits IL-10-mediated regulatory T cell function: implications for
      obesity.
AB  - Chronic inflammation is known to promote metabolic dysregulation in obesity and
      type 2 diabetes. Although the precise origin of the unchecked inflammatory
      response in obesity is unclear, it is known that overproduction of
      proinflammatory cytokines by innate immune cells affects metabolism. For example,
      TNF-alpha contributes to the inability of cells to respond to insulin and to the
      increase in levels of insulin. Whether this hyperinsulinemia itself is part of a
      feedback loop that affects the progression of chronic adipose inflammation is
      unknown. In this article, we show that regulatory T cells (Tregs) express the
      insulin receptor, and that high levels of insulin impair the ability of Tregs to
      suppress inflammatory responses via effects on the AKT/mTOR signaling pathway.
      Insulin activated AKT signaling in Tregs, leading to inhibition of both IL-10
      production and the ability of Tregs to suppress the production of TNF-alpha by
      macrophages in a contact-independent manner. The effect of insulin on Treg
      suppression was limited to IL-10 production and it did not alter the expression
      of other proteins associated with Treg function, including CTLA-4, CD39, and TGF
      beta. In a model of diet-induced obesity, Tregs from the visceral adipose tissue
      of hyperinsulinemic, obese mice showed a similar specific decrease in IL-10
      production, as well as a parallel increase in production of IFN-gamma. These data
      suggest that hyperinsulinemia may contribute to the development of obesity
      associated inflammation via a previously unknown effect of insulin on the IL-10
      mediated function of Tregs. 

PMID- 24323582
TI  - Quantitative analysis of protein turnover in plants.
AB  - Proteins are constantly being synthesised and degraded as plant cells age and as
      plants grow, develop and adapt the proteome. Given that plants develop through a
      series of events from germination to fruiting and even undertake whole organ
      senescence, an understanding of protein turnover as a fundamental part of this
      process in plants is essential. Both synthesis and degradation processes are
      spatially separated in a cell across its compartmented structure. The majority of
      protein synthesis occurs in the cytosol, while synthesis of specific components
      occurs inside plastids and mitochondria. Degradation of proteins occurs in both
      the cytosol, through the action of the plant proteasome, and in organelles and
      lytic structures through different protease classes. Tracking the specific
      synthesis and degradation rate of individual proteins can be undertaken using
      stable isotope feeding and the ability of peptide MS to track labelled peptide
      fractions over time. Mathematical modelling can be used to follow the isotope
      signature of newly synthesised protein as it accumulates and natural abundance
      proteins as they are lost through degradation. Different technical and biological
      constraints govern the potential for the use of (13)C, (15)N, (2)H and (18)O for
      these experiments in complete labelling and partial labelling strategies. Future
      development of quantitative protein turnover analysis will involve analysis of
      protein populations in complexes and subcellular compartments, assessing the
      effect of PTMs and integrating turnover studies into wider system biology study
      of plants.

PMID- 24323580
TI  - Therapeutic efficacy of suppressing the Jak/STAT pathway in multiple models of
      experimental autoimmune encephalomyelitis.
AB  - Pathogenic Th cells and myeloid cells are involved in the pathogenesis of
      multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an
      animal model of MS. The JAK/STAT pathway is used by numerous cytokines for
      signaling and is critical for development, regulation, and termination of immune
      responses. Dysregulation of the JAK/STAT pathway has pathological implications in
      autoimmune and neuroinflammatory diseases. Many of the cytokines involved in
      MS/EAE, including IL-6, IL-12, IL-23, IFN-gamma, and GM-CSF, use the JAK/STAT
      pathway to induce biological responses. Thus, targeting JAKs has implications for
      treating autoimmune inflammation of the brain. We have used AZD1480, a JAK1/2
      inhibitor, to investigate the therapeutic potential of inhibiting the JAK/STAT
      pathway in models of EAE. AZD1480 treatment inhibits disease severity in myelin
      oligodendrocyte glycoprotein-induced classical and atypical EAE models by
      preventing entry of immune cells into the brain, suppressing differentiation of
      Th1 and Th17 cells, deactivating myeloid cells, inhibiting STAT activation in the
      brain, and reducing expression of proinflammatory cytokines and chemokines.
      Treatment of SJL/J mice with AZD1480 delays disease onset of PLP-induced
      relapsing-remitting disease, reduces relapses and diminishes clinical severity.
      AZD1480 treatment was also effective in reducing ongoing paralysis induced by
      adoptive transfer of either pathogenic Th1 or Th17 cells. In vivo AZD1480
      treatment impairs both the priming and expansion of T cells and attenuates Ag
      presentation functions of myeloid cells. Inhibition of the JAK/STAT pathway has
      clinical efficacy in multiple preclinical models of MS, suggesting the
      feasibility of the JAK/STAT pathway as a target for neuroinflammatory diseases. 

PMID- 24323583
TI  - Do current animal models of intracerebral hemorrhage mirror the human pathology?
AB  - Although intracerebral hemorrhage (ICH) has no proven treatment, well-designed
      studies using animal models of ICH may lead to the development of novel
      therapies. We briefly review current animal models of ICH. Furthermore, we
      discuss how these models may be utilized and targeted to facilitate translation
      of preclinical findings to the clinical arena. 

PMID- 24323584
TI  - Association of CYP1A1 Gene Polymorphism with Ischemic Stroke in South Indian
      Population.
AB  - Stroke is a major cause of morbidity and mortality worldwide. Genetic and
      environmental factors are involved in the pathogenesis of stroke. Hypertension,
      diabetes mellitus, and cigarette smoking are the major risk factors, and smoking
      doubles the risk of ischemic stroke. Smoking cessation decreased the risk for
      ischemic stroke. CYP1A1 is the phase I metabolizing enzyme which plays a key role
      in metabolic activation of polycyclic aromatic hydrocarbons which are present in
      cigarette smoke and considered carcinogenic. So far, the association of CYP1A1
      gene polymorphism with stroke has not been investigated in Indian population. So,
      the study is taken up to evaluate the association of this polymorphism with
      ischemic stroke in a South Indian population. We genotyped 215 ischemic stroke
      patients and 162 age-matched controls using polymerase chain reaction-restriction
      fragment length polymorphism. Statistical analysis showed that CYP1A1 "CC"
      genotype is associated with five times increased risk of ischemic stroke (odds
      ratio (OR) = 5.14; 95% confidence interval (95% CI) = 1.14-23.14, p = 0.01),
      while "TT" (OR = 0.78, 95% CI = 0.51-1.19, p = 0.25) and "TC" (OR = 1.04, 95% CI
      = 0.67-1.60, p = 0.85) genotypes were nonsignificant with the increased risk of
      stroke. T and C allele frequencies in stroke were 76.5% and 23.5% as against
      81.8% and 18.2% in control group, respectively, thus, suggesting no statistically
      significant differences in the T (OR = 0.72, 95% CI = 0.50-1.03, p = 0.07) and C
      (OR = 1.37, 95% CI = 0.96-1.97, p = 0.07) allele frequencies between the two
      groups. The distribution of CYP1A1 genotypes and allelic frequency within the
      stroke subtypes showed a significant association of CC genotype only in
      intracranial large artery atherosclerosis (OR = 5.21, 95% CI = 1.03-26.38, p =
      0.02) while other subtypes did not show any association. Further analysis of
      CYP1A1 genotypes in patients and control subjects with smoking habit also showed
      a similar trend. Hence, we conclude that the CYP1A1 CC genotype is associated
      with the increased risk of ischemic stroke. 

PMID- 24323585
TI  - Dynamic Autoregulation Testing Does Not Indicate Changes of Cerebral Blood Flow
      Before and After Resection of Small- and Medium-Sized Cerebral AVM.
AB  - This study tested the hypothesis that dynamic cerebral autoregulation (AR)
      remains intact before and after the excision of human arteriovenous malformations
      (AVM). In 12 patients (six female and six male; mean age, 34 years) harboring
      cerebral AVMs (AVM group), and 15 patients (nine female/six male; mean age, 49
      years) with deep-seated lesions (e.g., small frontobasal meningiomas) approached
      by transsylvian dissection (control group), we continuously assessed cerebral
      blood flow (CBF) using a thermo-diffusion technique, and mean arterial blood
      pressure (MABP). AR was estimated post-hoc using correlation-coefficient
      autoregulatory-index (Mx) analysis. Measurements were compared according to
      groups (AVM/control) and times (pre/post), referred to as conditions before and
      after AVM resection and transsylvian dissection, respectively. All values are
      given as mean +/- SD. The correlation index Mx was without significant difference
      among the study groups, indicating unimpaired autoregulatory function. Intragroup
      comparisons related to AVM nidus size (small- (<=3 cm) and medium-sized (3-6 cm))
      did not show significant influence on autoregulation. The study shows that in
      patients harboring small- and medium-sized AVMs, dynamic autoregulatory function
      as estimated by correlation-coefficient index analysis seems to be intact in the
      surrounding cerebrovascular bed perioperatively. 

PMID- 24323586
TI  - Short period of early reperfusion aggravates blood-brain barrier dysfunction
      during permanent focal ischemia in rats.
AB  - Unintentional reperfusion is considered a complication in various experimental
      models of focal brain ischemia. In the present study, we evaluated whether short
      intermittent reperfusion affects ischemic brain damage and blood-brain barrier
      (BBB) integrity in a model of permanent focal ischemia. Focal brain ischemia was
      induced in male Sprague-Dawley rats using the filament method. A 20-s reperfusion
      period was allowed 0.5, 2, or 10 min after thread occlusion of the middle
      cerebral artery. In control animals, the transient reperfusion episode was
      omitted. The infarct volume and extent of swelling was examined 24 h after
      permanent thread occlusion. Immunohistochemical staining for thrombin
      extravasation was performed. Transient reperfusion early after thread occlusion
      augmented brain swelling (control, 12.4 +/- 8.5%; reperfusion after 0.5 min, 24.7
      +/- 7.0%*; after 2 min, 36.7 +/- 4.8%*; after 10 min, 33.8 +/- 4.9%*; *p < 0.01
      vs. control) and significantly enhanced leakage of the plasma protein thrombin,
      whereas the ischemic volume was unaffected. Early intermittent reperfusion may be
      responsible for increased BBB disruption in permanent ischemia. Similar
      reperfusion episodes during early ischemia sequelae in patients-due to incomplete
      adherence or distal movements of a clot-may be causative for increased BBB
      damage, more severe edema, and potentially hemorrhagic transformation. 

PMID- 24323587
TI  - A Combined Treatment with Taurine and Intra-arterial Thrombolysis in an Embolic
      Model of Stroke in Rats: Increased Neuroprotective Efficacy and Extended
      Therapeutic Time Window.
AB  - Combination treatment may target different pathophysiological events following
      cerebral ischemia thus enhancing the efficacy of treatment in thromboembolic
      stroke. Taurine confers a neuroprotective effect in the mechanical stroke model.
      This effect has not been assessed in an embolic stroke model. Here, we sought to
      evaluate the neuroprotective effect of taurine alone and in combination with
      thrombolytic therapy to investigate whether combined administration would extend
      the therapeutic time window without increasing the hemorrhagic transformation in
      a rat embolic stroke model. Rats were subjected to right embolic middle cerebral
      artery occlusion and then randomly assigned to the following groups: saline
      treatment alone at 4 h, urokinase, taurine treatment alone at 4, 6, or 8 h, and
      the combination of taurine and urokinase at 4, 6, or 8 h after the insult. Brain
      infarct volume, neurobehavioral outcome, regional cerebral blood flow,
      intracranial hemorrhage incidence were observed and evaluated. Posttreatment with
      taurine at 4 or 6 h, urokinase at 4 h or in combination at 4, 6, or 8 h
      significantly reduced infarct volume and improved neurobehavioral outcome. The
      combination treatment had better neurobehavioral outcome and smaller infarction
      volume than urokinase or taurine treatment alone. The clinical outcome correlated
      well with infarct volume. Together, the present study suggests that
      administration of taurine after stroke is neuroprotective, seemingly because it
      reduces the reperfusion damage of urokinase, leading to widen the therapeutic
      window for the thrombolytic effect of urokinase to 8 h. Thrombolysis can also
      enhance the neuroprotective effect of taurine. The reduction of inflammatory
      response, neuron death and inhibition of blood brain barrier (BBB) disruption may
      underlie the beneficial effects of combination of taurine and urokinase in the
      treatment of embolic stroke. 

PMID- 24323588
TI  - Investigation of the Interaction Between the Ser447Term Polymorphism of
      Lipoprotein Lipase and the Stroke-Related Risk Factors in Ischemic Stroke.
AB  - The present study aimed to investigate the interaction between the Ser447Term
      polymorphism in the lipoprotein lipase (LPL) gene and some common risk factors
      for stroke. A total of 704 unrelated patients with ischemic stroke were recruited
      for genetic analysis; they were all of Han Chinese origin. These patients were
      classified into subgroups based on their exposure to stroke-related risk factors,
      including type 2 diabetes, hypertension, smoking, and hyperlipidemia. The
      Ser447Term polymorphism was genotyped by PCR-based restriction fragment length
      polymorphism analysis. The chi-square (chi (2)) test showed that the frequency of
      Ser447Term G allele was significantly higher in stroke patients with a history of
      diabetes than in those without a history of diabetes (chi (2) = 7.25, P = 0.007,
      OR = 1.78, 95%CI 1.18-2.68). Allelic association was not observed in patients
      exposed to the other three stroke-related risk factors. The combined effect of
      the LPL gene polymorphisms and diabetes may contribute to the development of a
      subgroup of ischemic stroke. 

PMID- 24323589
TI  - Erratum: opportunities and challenges in omics.

PMID- 24323590
TI  - Periodic Epileptiform Discharges Clarified for the Nonneurologist Intensivist:
      Clinical Implications and Current Management.
AB  - Periodic epileptiform discharges (PEDs) are frequently encountered during
      continuous electroencephalography monitoring in the intensive care unit. Their
      implications and management are variable and highly dependent on the clinical
      context. This article is intended for the nonneurologist intensivist, reviews
      basic terminology and clinical implications (including causes, prognosis, and
      association with seizures), and suggests an approach to management. Several case
      vignettes are included to illustrate the clinical variability associated with
      PEDs. 

PMID- 24323592
TI  - The influence of age on clinical outcomes in patients treated with the resolute
      zotarolimus-eluting stent.
AB  - AIMS: To evaluate the rate of clinical events and bleeding risk according to age
      in patients undergoing percutaneous coronary intervention (PCI) with a new
      generation drug-eluting stent (DES) enrolled in the RESOLUTE Global Clinical
      Program. METHODS: This study represents a pooled analysis of five trials included
      in the RESOLUTE program including 5,130 patients, of whom 1,675 (32.6%) were >=70
      years old (elderly patients). RESULTS: After adjusting for confounders, age >=70
      years was a significant predictor of high mortality at 30 days (0.6 vs. 0.1%, P =
      0.017) and 2 years (7.2 vs. 2%, P < 0.001). No differences were seen with respect
      to acute myocardial infarction (MI) or target lesion and vessel revascularization
      rates between young and elderly patients. Bleeding rates were higher in the
      elderly throughout follow-up. In the elderly, 7 of the 27 (26%) patients with
      bleeding episodes died, with a median time between bleeding episode to death of
      21 days. In the younger population, 1 patient of 17 with a bleeding episode died
      (400 days later). CONCLUSIONS: Elderly patients undergoing PCI with a new
      generation DES have increased mortality and bleeding risk, with similar rates of
      acute MI and repeat revascularization. Bleeding risk was higher in the elderly
      and strongly related to death. Target lesion failure rates were not significantly
      different between the two age groups, suggesting that the Resolute zotarolimus
      eluting stent (R-ZES) is effective for patients younger and older than 70 years
      of age. R-ZES may be recommended for elderly patients when PCI with a DES is
      identified as a suitable option.

PMID- 24323593
TI  - Age-specific effectiveness and safety of newly initiated insulin therapy in
      Japanese patients with uncontrolled diabetes.
AB  - INTRODUCTION: One consequence of population aging is an increase in the number of
      elderly patients with diabetes mellitus. These elderly patients often experience
      atherosclerotic complications, and diabetes prevention and management are
      strongly desired to promote health and reduce the financial burden on the
      healthcare system. In this study, we conducted an age-specific evaluation of the
      effectiveness and safety of comprehensive management with newly initiated insulin
      therapy over a 1-year period in elderly (>=65 years) compared with non-elderly
      (<=64 years) Japanese patients with uncontrolled diabetes [glycated hemoglobin
      (HbA1c) >= 8% for >= 3 months]. METHODS: This retrospective single-center cohort
      study was conducted in Japan. We screened all outpatients with diabetes mellitus
      who visited the clinic for diabetes treatment between December 2006 and March
      2011. Of these patients, 132 with type 2 diabetes who were newly initiated on
      insulin therapy for continued poor glycemic control and undergoing comprehensive
      management through self-monitoring of blood glucose (SMBG) were registered to the
      study. RESULTS: Thirty-two of 132 registered patients were excluded from the
      analysis. Among the 100 patients (67 non-elderly, 33 elderly) included in the
      analysis, median age and proportion of male patients was 69 years and 66.7%,
      respectively, among the elderly, and 52 years and 68.7%, respectively, among the
      non-elderly patients. After initiation of insulin therapy, median HbA1c levels
      improved from 9.6% to 7.2% in elderly patients, and from 10.8% to 7.3% in non
      elderly patients at baseline and 12 months. Severe hypoglycemic events were not
      observed in either patient group; however, uncontrolled diabetes was ongoing in
      31.8% of non-elderly and 15.4% of elderly patients, and obesity was associated
      with poor glycemic control. CONCLUSION: Our results indicate that the
      effectiveness and safety of newly initiated insulin therapy are similar between
      elderly and non-elderly Japanese patients with uncontrolled diabetes, and
      highlight the importance of comprehensive management using SMBG to avoid
      hypoglycemia. Better glycemic control supported by adequate intensive management
      is required to improve mortality and morbidity.

PMID- 24323591
TI  - Advances and future directions in the targeting of HER2-positive breast cancer:
      implications for the future.
AB  - OPINION STATEMENT: The natural history of HER2-positive breast cancer
      significantly changed in the past 15 years. Form being the most aggressive type
      of breast cancer, it became treatable with important cure rates. However, with
      new and successful drugs, resistance emerges. Progress in research and drug
      development continues to make available effective anti-HER2 therapies. Our
      challenge today is to use these tools correctly by looking at the data that
      support the indications of each compound and to continue clinical trial
      participation.

PMID- 24323594
TI  - Periostin improves cell adhesion to implantable biomaterials and osteoblastic
      differentiation on implant titanium surfaces in a topography-dependent fashion.
AB  - Periostin is a matricellular protein highly expressed in periodontal ligament and
      periostium and has been shown to be required for tissue development and
      maintenance. We showed that the adhesion of murine osteoblastic MC3T3 cells to
      thiolated hyaluronic acid/polyethyleneglycol hydrogels was greatly improved by
      enrichment with periostin. Polished or sand-blasted/acid-etched (SLA)
      commercially pure titanium surfaces were also coated with this protein and
      periostin ameliorated cell adhesion and dramatically affected cell morphology on
      both surfaces, as assessed at fluorescence microscopy, scanning electron
      microscopy, and chemiluminescence-based viability assay. Moreover, periostin
      increased the expression of alkaline phosphatase, osteoprotegerin, connective
      tissue growth factor, collagen 1a1, osteocalcin, Runx2, and osterix transcription
      factors on smooth surfaces. However, it did not affect, or even decreased, the
      expression of these genes on SLA discs. Transcript levels for connexin 43 were
      greatly increased on both surfaces in the presence of periostin. Taken together,
      these results show that periostin coatings can be a viable approach to improve
      cell adhesion and differentiation on implantable biomaterials.

PMID- 24323615
TI  - Axillary lymph node dissection versus no dissection in patients with T1N0 breast
      cancer: a randomized clinical trial (INT09/98).
AB  - BACKGROUND: Although axillary surgery is still considered to be a fundamental
      part of the management of early breast cancer, it may no longer be necessary
      either as treatment or as a guide to adjuvant treatment. The authors conducted a
      single-center randomized trial (INT09/98) to determine the impact of avoiding
      axillary surgery in patients with T1N0 breast cancer and planning chemotherapy
      based on biological factors of the primary tumor on long-term disease control.
      METHODS: From June 1998 to June 2003, 565 patients aged 30 years to 65 years with
      T1N0 breast cancer were randomized to either quadrantectomy with (QUAD) or
      without (QU) axillary lymph node dissection; a total of 517 patients finally were
      evaluated. All patients received radiotherapy to the residual breast only.
      Chemotherapy for patients in the QUAD treatment arm was determined based on lymph
      node status, estrogen receptor status, and tumor grade. Chemotherapy for patients
      in the QU treatment arm was based on estrogen receptor status, tumor grade, and
      human epidermal growth factor receptor 2 and laminin receptor status. Overall
      survival (OS) was the primary endpoint. Disease-free survival (DFS) and rate and
      time of axillary lymph node recurrence in the QU treatment arm were the secondary
      endpoints. RESULTS: After a median follow-up of >10 years, the estimated adjusted
      hazards ratio of the QUAD versus QU treatment arms for OS was 1.09 (95%
      confidence interval, 0.59-2.00; P = .783) and was 1.04 (95% confidence interval,
      0.56-1.94; P = .898) for DFS. Of the 245 patients in the QU treatment arm, 22
      (9.0%) experienced axillary lymph node recurrence. The median time to axillary
      lymph node recurrence from breast surgery was 30.0 months (interquartile range,
      24.2 months-73.4 months). CONCLUSIONS: Patients with T1N0 breast cancer did not
      appear to benefit in terms of DFS and OS from immediate axillary lymph node
      dissection in the current randomized trial. The biological characteristics of the
      primary tumor appear adequate for guiding adjuvant treatment.

PMID- 24323616
TI  - Scale criticality in estimating ecosystem carbon dynamics.
AB  - Scaling is central to ecology and Earth system sciences. However, the importance
      of scale (i.e. resolution and extent) for understanding carbon dynamics across
      scales is poorly understood and quantified. We simulated carbon dynamics under a
      wide range of combinations of resolution (nine spatial resolutions of 250 m, 500
      m, 1 km, 2 km, 5 km, 10 km, 20 km, 50 km, and 100 km) and extent (57 geospatial
      extents ranging from 108 to 1 247 034 km(2) ) in the southeastern United States
      to explore the existence of scale dependence of the simulated regional carbon
      balance. Results clearly show the existence of a critical threshold resolution
      for estimating carbon sequestration within a given extent and an error limit.
      Furthermore, an invariant power law scaling relationship was found between the
      critical resolution and the spatial extent as the critical resolution is
      proportional to A(n) (n is a constant, and A is the extent). Scale criticality
      and the power law relationship might be driven by the power law probability
      distributions of land surface and ecological quantities including disturbances at
      landscape to regional scales. The current overwhelming practices without
      considering scale criticality might have largely contributed to difficulties in
      balancing carbon budgets at regional and global scales.

PMID- 24323617
TI  - Magnetic resonance support vector machine discriminates between Parkinson disease
      and progressive supranuclear palsy.
AB  - BACKGROUND: The aim of the current study was to distinguish patients with
      Parkinson disease (PD) from those with progressive supranuclear palsy (PSP) at
      the individual level using pattern recognition of magnetic resonance imaging
      data. METHODS: We combined diffusion tensor imaging and voxel-based morphometry
      in a support vector machine algorithm to evaluate 21 patients with PSP and 57
      patients with PD. RESULTS: The automated algorithm correctly distinguished
      patients who had PD from those who had PSP with 100% accuracy. This accuracy
      value was obtained when white matter atrophy was considered. Diffusion parameters
      combined with gray matter atrophy exhibited 90% sensitivity and 96% specificity.
      CONCLUSIONS: Our findings demonstrate that automated pattern recognition can help
      distinguish patients with PSP from those with PD on an individual basis.

PMID- 24323618
TI  - Metrics for covariate balance in cohort studies of causal effects.
AB  - Inferring causation from non-randomized studies of exposure requires that
      exposure groups can be balanced with respect to prognostic factors for the
      outcome. Although there is broad agreement in the literature that balance should
      be checked, there is confusion regarding the appropriate metric. We present a
      simulation study that compares several balance metrics with respect to the
      strength of their association with bias in estimation of the effect of a binary
      exposure on a binary, count, or continuous outcome. The simulations utilize
      matching on the propensity score with successively decreasing calipers to produce
      datasets with varying covariate balance. We propose the post-matching C-statistic
      as a balance metric and found that it had consistently strong associations with
      estimation bias, even when the propensity score model was misspecified, as long
      as the propensity score was estimated with sufficient study size. This metric,
      along with the average standardized difference and the general weighted
      difference, outperformed all other metrics considered in association with bias,
      including the unstandardized absolute difference, Kolmogorov-Smirnov and Levy
      distances, overlapping coefficient, Mahalanobis balance, and L1 metrics. Of the
      best-performing metrics, the C-statistic and general weighted difference also
      have the advantage that they automatically evaluate balance on all covariates
      simultaneously and can easily incorporate balance on interactions among
      covariates. Therefore, when combined with the usual practice of comparing
      individual covariate means and standard deviations across exposure groups, these
      metrics may provide useful summaries of the observed covariate imbalance.

PMID- 24323619
TI  - Targeting the Microvasculature in Cerebral Ischemia-Go (or Stop Going) with the
      Flow.

PMID- 24323620
TI  - Cerebral blood flow measurement in neurosurgery.
AB  - Cerebral blood flow (CBF) is the key factor for identifying progressive
      hypoperfusion that is indicative of numerous pathological conditions. CBF
      measurement is beneficial for the management of cerebrovascular disease, head
      injury, and intracranial neoplasms. Of the various imaging modalities developed
      to assess CBF, the most notable are positron emission tomography, single photon
      emission computed tomography (CT), xenon CT, magnetic resonance imaging, and
      perfusion CT. The authors review the advancements in each modality, especially
      focusing on perfusion CT in neurosurgical applications and the value of
      acetazolamide challenge during scanning. Software developments have delivered
      important improvements in processing perfusion data by eliminating the necessity
      of manually drawing a region of interest (ROI) on each image. Rather, the
      software enables a digitized ROI template to be applied to each scan for better
      reproducibility and consistent results. Finally, in assessing CT perfusion for
      measuring cerebral blood flow in neurosurgical patients, we compare its benefits
      and limitations with other commonly used imaging methods. 

PMID- 24323623
TI  - "Bio"-macromolecules: polymer-protein conjugates as emerging scaffolds for
      therapeutics.
AB  - Polymer-protein conjugates are biohybrid macromolecules derived from covalently
      connecting synthetic polymers with polypeptides. The resulting materials combine
      the properties of both worlds: chemists can engineer polymers to stabilize
      proteins, to add functionality, or to enhance activity; whereas biochemists can
      exploit the specificity and complexity that Nature has bestowed upon its
      macromolecules. This has led to a wealth of applications, particularly within the
      realm of biomedicine. Polymer-protein conjugation has expanded to include
      scaffolds for drug delivery, tissue engineering, and microbial inhibitors. This
      feature article reflects upon recent developments in the field and discusses the
      applications of these hybrids from a biomaterials standpoint. 

PMID- 24323621
TI  - Sonothrombolysis: an emerging modality for the treatment of acute ischemic and
      hemorrhagic stroke.
AB  - To date, it is believed that rapid removal of impedances hindering normal blood
      circulation in the brain would salvage ischemic tissue. Hence, most treatment
      modalities undergoing clinical evaluation for treatment of stroke are focused on
      faster recanalization in acute ischemic stroke or faster hematoma mass reduction
      in hemorrhagic stroke. Therapeutic ultrasound is among the promising emerging
      modalities being clinically evaluated to meet this purpose. This review provides
      an overview of existing clinical data in evaluating sonothrombolysis applications
      in treatment of acute ischemic and hemorrhagic stroke. Furthermore, the present
      status of clinical evaluation of microbubbles as a potential adjuvant to this
      modality is reviewed. 

PMID- 24323622
TI  - Dipyridamole Treatment Prior to Stroke Onset: Examining Post-stroke Cerebral
      Circulation and Outcome in Rabbits.
AB  - Clinical observations have indicated that secondary treatment with dipyridamole
      (DIP) may ameliorate stroke severity. The purpose of this study was to explore
      the effect of pre-stroke DIP treatment on stroke outcome in a rabbit model of
      embolic occlusion. Twenty male New Zealand white rabbits were randomly selected
      for intravenous treatment with DIP (n = 10) or saline (n = 10) for 7 days prior
      to an embolic cerebral occlusion by an autologous blood clot. Multiple computed
      tomography perfusion scans were acquired out to 28 days post-stroke to map
      cerebrohemodynamics, in conjunction with neurological assessments and
      histopathology. The DIP-treated group fared better than the saline group on
      several accounts: 66% of them survived to 28 days, whilst saline animals all had
      to be euthanized by day 7 due to severe neurological deficits. They presented
      with significantly more viable tissue in the ischemic hemisphere as well as fewer
      neurological deficits on days 4 and 7. Furthermore, DIP-treated animals exhibited
      improved cerebrohemodynamics by 24 h and had less incidence of haemorrhage within
      their infarcted regions (p < 0.05). DIP treatment prior to stroke onset can
      significantly improve neurological outcome, cerebral hemodynamics, and final
      infarct volume. 

PMID- 24323624
TI  - SABRE2: a database connecting plant EST/full-length cDNA clones with Arabidopsis
      information.
AB  - The SABRE (Systematic consolidation of Arabidopsis and other Botanical REsources)
      database cross-searches plant genetic resources through publicly available
      Arabidopsis information. In SABRE, plant expressed sequence tag (EST)/cDNA clones
      are related to TAIR (The Arabidoposis Information Resource) gene models and their
      annotations through sequence similarity. By entering a keyword, SABRE searches
      and retrieves TAIR gene models and annotations, together with homologous gene
      clones from various plant species. SABRE thus facilitates using TAIR annotations
      of Arabidopsis genes for research on homologous genes from other model plants. To
      expand the application range of SABRE to crop breeding, we have recently upgraded
      SABRE to SABRE2 (http://sabre.epd.brc.riken.jp/SABRE2.html), by newly adding six
      model plants (including the major crops barley, soybean, tomato and wheat), and
      by improving the retrieval interface. The present version has integrated
      information on >1.5 million plant EST/cDNA clones from the National BioResource
      Project (NBRP) of Japan. All clones are actual experimental resources from 14
      plant species (Arabidoposis, barley, cassava, Chinese cabbage, lotus, morning
      glory, poplar, Physcomitrella patens, Striga hermonthica, soybean, Thellungiella
      halophila, tobacco, tomato and wheat), and are available from the core facilities
      of the NBRP. SABRE2 is thus a useful tool that can contribute towards the
      improvement of important crop breeds by connecting basic research and crop
      breeding. 

PMID- 24323625
TI  - Salinity acclimation enhances salinity tolerance in tadpoles living in brackish
      water through increased Na+ , K+ -ATPase expression.
AB  - Amphibians are highly susceptible to osmotic stress but, nonetheless, some
      species can adapt locally to withstand moderately high levels of salinity.
      Maintaining the homeostasis of body fluids by efficient osmoregulation is thus
      critical for larval survival in saline environments. We studied the role of
      acclimation in increased physiological tolerance to elevated water salinity in
      the Indian rice frog (Fejervarya limnocharis) tadpoles exposed to brackish water.
      We quantified the effects of salinity acclimation on tadpole survival,
      osmolality, water content, and gill Na+ , K+ -ATPase (NKA) expression. Tadpoles
      did not survive over 12 hr if directly transferred to 11 ppt (parts per thousand)
      whereas tadpoles previously acclimated for 48 hr in 7  ppt survived at least 48
      hr. We reared tadpoles in 3 ppt and then we transferred them to one of (a) 3 ppt,
      (b) 11  ppt, and (c) 7  ppt for 48 hr and then 11 ppt. In the first 6 hr after
      transfer to 11 ppt, tadpole osmolality sharply increased and tadpole water
      content decreased. Tadpoles pre-acclimated for 48 hr in 7 ppt were able to
      maintain lower and more stable osmolality within the first 3 hr after transfer.
      These tadpoles initially lost water content, but over the next 6 hr gradually
      regained water and stabilized. In addition, they had a higher relative abundance
      of NKA proteins than tadpoles in other treatments. Pre-acclimation to 7 ppt for
      48 hr was hence sufficient to activate NKA expression, resulting in increased
      survivorship and reduced dehydration upon later transfer to 11 ppt. J

PMID- 24323626
TI  - Treatment of stage II-III rectal cancer patients.
AB  - The role and sequencing of radiotherapy in the management of T3-4 or node
      positive rectal cancer has evolved over the last few decades. Given the
      significant local failure rate following surgery alone, both preoperative and
      postoperative chemotherapy and radiotherapy have been studied to decrease local
      and systemic failure and improve survival in these patients. This review
      discusses current indications and controversies for treatment of stage II-III
      rectal cancer patients. 

PMID- 24323627
TI  - How to resolve the caudal septal deviation? Clinical outcomes after septoplasty
      with bony batten grafting.
AB  - OBJECTIVES/HYPOTHESIS: Caudal septal deviation interrupts normal nasal breathing,
      due to the narrowing of the external valve area and nasal valve angle. In this
      study, we found a different approach for correction of caudal septal deviation
      with no associated deformity of the external nose. STUDY DESIGN: Individual case
      control study. METHODS: The 39 patients completed questionnaires by interviews
      postoperatively for assessment of nasal obstruction. In addition, patients
      assessed the severity of their nasal symptoms (i.e., mouth breathing, mouth
      dryness, hyposmia, rhinorrhea, epistaxis, snoring, postnasal drip, and headache)
      preoperatively and postoperatively using a visual analog scale (VAS). Improvement
      in the treatment of nasal obstruction using a VAS and a questionnaire for
      subjective satisfaction were evaluated 3 months after septoplasty. To evaluate
      outcomes objectively, endoscopic photographs of the nasal cavity and acoustic
      rhinometry before and after surgery were evaluated. For comparison between
      preoperative and postoperative status, the Wilcoxon signed ranks test was used.
      RESULTS: Patients reported a significant decrease in the VAS severity of all
      nasal symptoms. The minimal cross-sectional area (MCA1) of the convex side after
      vascular constriction using acoustic rhinometry showed significant widening.
      Patients were divided into a turbinoplasty group and a nonturbinoplasty group,
      and the turbinoplasty group showed a significant increase in both the convex side
      and concave side in MCA1 and in the convex side in the anterior portion of the
      inferior turbinate. CONCLUSIONS: Endonasal septoplasty using bony batten grafting
      for caudal septal deviation resulted in an improvement of nasal obstruction
      symptoms and acoustic rhinometry components.

PMID- 24323628
TI  - [Acceptance, utility and practicality of a questionnaire to define rehabilitation
      goals before the commencement of the medical rehabilitation].
AB  - BACKGROUND AND GOALS: In a multicenter study, patients of the German statutory
      insurance were encouraged to deal with their own rehabilitation goals using a
      questionnaire sent in advance of rehabilitation. How patients and physicians
      assess the benefits and practicability of this method should, in particular, be
      examined. METHODS: In a randomized controlled study a questionnaire, based on the
      preparation booklet of the DRV Bund, was sent by the German statutory insurance
      to 2782 rehabilitation patients (n(ortho)=1406, n(onco)714, n(psy)=662). For the
      intervention group, the questionnaire included, in addition to general
      information about rehabilitation goals, free text fields for the formulation of
      own goals. Patients were asked to bring the completed questionnaire to the
      admission interview. At the end of rehabilitation, satisfaction with
      participation in the goal-setting process and perceived usefulness of information
      on rehabilitation goals were captured. The doctors/psychologists responded to
      standardized items regarding various aspects of utility and practicability of the
      questionnaire. RESULTS: 34% of the targeted rehabilitation patients brought the
      completed questionnaire to the admission interview. For most of the
      rehabilitation patients goal setting is important; 31.4% reported the information
      obtained to rehabilitation goals to be very, and 62.9% particularly helpful. For
      practitioners, the questionnaire is likely to orient rehabilitation patients to
      rehabilitation goals: they reported that 56.6% of the patients reflected about
      their goals and that 50% were more familiar with the subject. Physicians rated
      the handling and integration of the questionnaire into the interview, its format
      and layout as well as its benefits more positively than the surveyed
      psychologists. These were more optimistic about the ability of rehabilitation
      patients to answer the questionnaire (62.5%, physicians 47.2%) and define own
      goals (77.8%, physicians 41.7%). CONCLUSIONS: The applied questionnaire has been
      well accepted by the majority of rehabilitation patients and practitioners as
      well as was judged to be practical and useful in important aspects. A
      comprehensive implementation of the questionnaire proves to be promising,
      particularly in the context of oncological and orthopedic rehabilitation. To
      increase the return of the questionnaire, alternative delivery options should be
      explored in future. Against the background that rehabilitation patients and
      practitioners of psychosomatic medicine perceived the questionnaire as less
      helpful, it is also prudent to investigate whether indication-specific
      implementation strategies would be advantageous.

PMID- 24323629
TI  - [Validity and responsiveness of the Scales for the Assessment of Functioning at
      Work].
AB  - The Scales for the Assessment of Functioning at Work (SE-FFB) allow for an ICF
      oriented assessment of patient reported work performance and symptoms at work.
      The aim of the study is to test convergent end discriminate validity through
      correlations with measures that are typically applied in rehabilitation and
      responsiveness by means of description of the change in the course of
      rehabilitation (t0=beginning of the rehabilitation, t1=3 months after
      rehabilitation). The sample comprises 249 rehabilitation patients with
      musculoskeletal diseases. The correlations of the SE-FFB with the criteria of
      convergent and discriminate validity are in accordance with the expectations. For
      women medium effects were found, indicating better work performance and fewer
      symptoms 3 months after rehabilitation, for men the effects were small. The SE
      FFB allows for a reliable, valid and responsive assessment of the working
      situation. 

PMID- 24323630
TI  - [DGRW-update: relevance and evidence of pulmonary rehabilitation in chronic
      obstructive respiratory diseases (adults)].
AB  - According to current guidelines, pulmonary rehabilitation is an essential part of
      the long-term management of the widespread diseases COPD and asthma, of which 11
      million people in Germany are currently affected. The body of scientific evidence
      assuring the relevant positive effects of rehabilitation is of the highest level,
      especially in the case of COPD. These range from improvement in the major
      clinical symptoms of shortness of breath and diminished vitality, the reduction
      of the psychosocial consequences of the disease in terms of secondary anxiety and
      depression, the reduction of sick days and hospital stays to reduced patient
      mortality rates after hospitalization for COPD. Considering the enormous medical
      as well as socio-economic relevance of chronic obstructive pulmonary disease, the
      convincing body of evidence and the high levels of recommendation in evidence
      based guidelines, there is a striking disparity with regard to those
      rehabilitation measures actually carried out, which, according to German national
      statutory pension insurance, account for less than 3% of all completed medical
      rehabilitation measures. 

PMID- 24323632
TI  - Acupuncture in De Quervain's disease: a treatment proposal.
AB  - De Quervain's disease is a painful stenosing tenosynovitis of the first dorsal
      compartment of the hand affecting the tendons of the abductor pollicis longus and
      extensor pollicis brevis, caused mainly by overuse. Conventional treatments
      include rest, immobilisation, oral anti-inflammatory drugs, corticosteroid
      injection and even surgery, but none of these is established as clearly
      effective. Acupuncture is rarely mentioned and the points suggested are rather
      general-regional, tender and ah shi points. Tendinopathy is almost always
      associated with problems in the relevant muscles and this paper calls attention
      to the correct identification and needling of the affected muscles, in order to
      increase the specificity of acupuncture treatment. 

PMID- 24323631
TI  - Soluble tumor necrosis factor receptors and heart failure risk in older adults:
      Health, Aging, and Body Composition (Health ABC) Study.
AB  - BACKGROUND: Tumor necrosis factor (TNF) levels are associated with risk for heart
      failure (HF). The soluble TNF type 1 (sTNF-R1) and type 2 (sTNF-R2) receptors are
      elevated in patients with manifest HF, but whether they are associated with risk
      for incident HF is unclear. METHODS AND RESULTS: Using Cox proportional hazard
      models, we examined the association between baseline levels of sTNF-R1 and sTNF
      R2 with incident HF risk among 1285 participants of the Health, Aging, and Body
      Composition Study (age, 74.0+/-2.9 years; 51.4% women; 41.1% black). At baseline,
      median (interquartile range) of TNF, sTNF-R1, and sTNF-R2 levels was 3.14 (2.42
      4.06), 1.46 (1.25-1.76), and 3.43 (2.95-4.02) ng/mL, respectively. During a
      median follow-up of 11.4 (6.9-11.7) years, 233 (18.1%) participants developed HF.
      In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28;
      95% confidence interval [CI], 1.02-1.61 per log2 increase) and sTNF-R1 (HR, 1.68;
      95% CI, 1.15-2.46 per log2 increase), but not sTNF-R2 (HR, 1.15; 95% CI, 0.80
      1.63 per log2 increase), were associated with a higher risk for HF. These
      associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2;
      interaction P=0.531, 0.091, and 0.795, respectively) and in both sexes (TNF, sTNF
      R1, sTNF-R2; interaction P=0.491, 0.672, and 0.999, respectively). TNF-R1 was
      associated with a higher risk for HF with preserved versus reduced ejection
      fraction (HR, 1.81; 95% CI, 1.03-3.18; P=0.038 for preserved versus HR, 0.90; 95%
      CI, 0.56-1.44; P=0.667 for reduced ejection fraction; interaction P=0.05).
      CONCLUSIONS: In older adults, elevated levels of sTNF-R1 are associated with
      increased risk for incident HF. However, addition of TNF-R1 to the previously
      validated Health ABC HF risk model did not demonstrate material improvement in
      net discrimination or reclassification.

PMID- 24323633
TI  - Benefits of acupuncture for diabetic gastroparesis: a comparative preliminary
      study.
AB  - OBJECTIVES: The aim of this preliminary study was to compare the effectiveness of
      domperidone and acupuncture for the management of diabetic gastroparesis.
      METHODS: This was a preliminary, prospective non-randomised, unblinded case
      crossover study conducted in patients with longstanding, uncontrolled diabetes
      mellitus and gastroparesis. All patients received domperidone (20 mg four times a
      day) for 12 weeks, followed by a 2-3 week washout period, and then biweekly
      acupuncture treatments for 8 weeks. Gastric emptying rate, glucose and glycated
      haemoglobin (HbA1C) levels were measured at start and end of each treatment
      period. At each of these timepoints patients completed the Gastroparesis Cardinal
      Symptom Index (GCSI), the Satisfaction with Life Scale (SWLS), and the Short-Form
      36 Health Survey Update (SF-36). RESULTS: The trial was curtailed after only
      eight participants could be recruited in 3 years. The mean age of patients was
      57.1+/-9.9 years, the male:female ratio was 1:7 and mean body mass index
      (kg/m(2)) was 25.2+/-1.2. There was no change in any of the outcome parameters
      after treatment with domperidone. Acupuncture was associated with a decrease in
      scores for almost all cardinal symptoms of the GCSI, as well as in increased
      total score on the SWLS (p=0.002) and the social functioning domain of the SF-36
      (p=0.054). Acupuncture did not lead to an improvement in gastric emptying, or
      glucose control from baseline. CONCLUSIONS: Acupuncture treatment may lead to
      symptomatic improvement in patients with diabetic gastroparesis. Within the
      limitations of this preliminary, non-randomised and unblinded study, it appears
      that this effect may be due to non-specific mechanisms.

PMID- 24323634
TI  - Solely abluminal drug release from coronary stents could possibly improve
      reendothelialization.
AB  - OBJECTIVES: To compare a new stent with an asymmetric coating, eluting the drug
      to the abluminal surface, to a stent with a conventional coating eluting the drug
      both to the luminal and the abluminal side. BACKGROUND: Stents with asymmetric
      coating, eluting the drug to the vessel wall (BPSES-A), could potentially give
      faster reendothelialization after percutaneous coronary interventions (PCI) and
      decrease in in-stent thrombosis and late restenosis. METHODS: BPSES-A,
      conventional coated stents (BPSES-C), biodegradable polymer stents without drug
      (BPS, for control), and bare metal stents (BMS, for control) were implanted into
      the coronary arteries of 38 pigs (75 stents). Pigs were sacrificed after 4, 12,
      and 24 weeks. Quantitative coronary angiography was used to compare in-stent late
      lumen loss (LLL) and electron microscopy was used to reveal levels of
      reendothelialization. RESULTS: The stents were all successfully implanted. LLL of
      BPSES-A, BPSES-C, BMS, and BPS were 0.56 +/- 0.51, 0.60 +/- 0.58, 0.89 +/- 0.43,
      and 1.68 +/- 0.30 mm, respectively, after 4 weeks. LLL of BPSES-A and BPSES-C
      were 0.63 +/- 0.53 and 0.69 +/- 0.24 mm, respectively, after 12 weeks. LLL of
      BPSES-A, BPSES-C, and BMS were 0.42 +/- 0.15 m, 0.56 +/- 0.28 mm, and 0.99 +/-
      0.13 mm, respectively, after 24 weeks. The scaling of reendothelialization was as
      follows: after 4 weeks BMS > = BPS > BPSES-A > BPSES-C, after 12 weeks BPSES-A >
      BPSES-C, and after 24 weeks BMS > BPSES-A > BPSES-C. Reendothelialization was
      better in BPSES-A than BPSES-C (P < 0.05). There was no correlation between LLL
      and reendothelialization (P = 0.42). CONCLUSION: Asymmetric coating of coronary
      stents might be helpful to improve reendothelialization. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 24323635
TI  - Prevalence, genetic diversity and recombination of species G enteroviruses
      infecting pigs in Vietnam.
AB  - Picornaviruses infecting pigs, described for many years as 'porcine
      enteroviruses', have recently been recognized as distinct viruses within three
      distinct genera (Teschovirus, Sapelovirus and Enterovirus). To better
      characterize the epidemiology and genetic diversity of members of the Enterovirus
      genus, faecal samples from pigs from four provinces in Vietnam were screened by
      PCR using conserved enterovirus (EV)-specific primers from the 5' untranslated
      region (5' UTR). High rates of infection were recorded in pigs on all farms, with
      detection frequencies of approximately 90% in recently weaned pigs but declining
      to 40% in those aged over 1 year. No differences in EV detection rates were
      observed between pigs with and without diarrhoea [74% (n = 70) compared with 72%
      (n = 128)]. Genetic analysis of consensus VP4/VP2 and VP1 sequences amplified
      from a subset of EV-infected pigs identified species G EVs in all samples. Among
      these, VP1 sequence comparisons identified six type 1 and seven type 6 variants,
      while four further VP1 sequences failed to group with any previously identified
      EV-G types. These have now been formally assigned as EV-G types 8-11 by the
      Picornavirus Study Group. Comparison of VP1, VP4/VP2, 3D(pol) and 5' UTRs of
      study samples and those available on public databases showed frequent, bootstrap
      supported differences in their phylogenies indicative of extensive within-species
      recombination between genome regions. In summary, we identified extremely high
      frequencies of infection with EV-G in pigs in Vietnam, substantial genetic
      diversity and recombination within the species, and evidence for a much larger
      number of circulating EV-G types than currently described.

PMID- 24323636
TI  - Interferon-beta and mycophenolic acid are potent inhibitors of Middle East
      respiratory syndrome coronavirus in cell-based assays.
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel
      emerging threat to public health worldwide. Several treatments for infected
      individuals have been suggested including IFN, ribavirin and passive
      immunotherapy with convalescent plasma. Administration of IFN-alpha2b and
      ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when
      administered within 8 h post-challenge. However, detailed and systematic evidence
      on the activity of other clinically available drugs is limited. Here we compared
      the susceptibility of MERS-CoV with different IFN products (IFN-alpha2b, IFN
      gamma, IFN-universal, IFN-alpha2a and IFN-beta), as well as with two antivirals,
      ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in
      vitro. Of all the IFNs tested, IFN-beta showed the strongst inhibition of MERS
      CoV in vitro, with an IC50 of 1.37 U ml(-1), 41 times lower than the previously
      reported IC50 (56.08 U ml(-1)) of IFN-alpha2b. IFN-beta inhibition was confirmed
      in the virus yield reduction assay, with an IC90 of 38.8 U ml(-1). Ribavirin did
      not inhibit viral replication in vitro at a dose that would be applicable to
      current treatment protocols in humans. In contrast, MPA showed strong inhibition,
      with an IC50 of 2.87 uM. This drug has not been previously tested against MERS
      CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In
      conclusion, IFN-beta, MPA or a combination of the two may be beneficial in the
      treatment of MERS-CoV or as a post-exposure intervention in high-risk patients
      with known exposures to MERS-CoV.

PMID- 24323637
TI  - Unusual characteristics of dicistrovirus-derived small RNAs in the small brown
      planthopper, Laodelphax striatellus.
AB  - In this study, sequences of small RNA (sRNA) libraries derived from the insect
      vector Laodelphax striatellus were assembled into contigs and used as queries for
      database searches. A large number of contigs were highly homologous to the genome
      sequence of an insect dicistrovirus, himetobi P virus (HiPV). Interestingly, HiPV
      derived sRNAs had a wide size distribution, and were relatively abundant
      throughout the 18-30 nt size range with only a slight peak at 22 nt. HiPV sRNAs
      had a strong bias towards the sense strand, whilst the antisense sRNAs were
      predominantly 21 and 22 nt. HiPV sRNAs do not have the typical features of PIWI
      interacting RNAs, but their 3' ends were preferentially cleaved at UA-rich
      sequences. Our data suggest that HiPV sRNAs may be derived both from activities
      of the RNA interference pathway and from cleavage of the viral genome by other
      host RNases. 

PMID- 24323638
TI  - Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for
      secondary dengue virus infection: high levels of viraemia and serotype cross
      reactive antibody responses consistent with secondary infection of humans.
AB  - There are four dengue virus (DENV) serotypes. Primary infection with one does not
      confer protective immunity against the others. We have reported previously that
      the marmoset (Callithrix jacchus) is a useful primary DENV infection model. It
      has been reported that secondary DENV infection with a heterotypic serotype
      induces viraemia kinetics and antibody responses that differ from those in
      primary infection. Thus, it is important to determine the utility of the marmoset
      as a model for secondary DENV infection. Marmosets were infected with
      heterologous DENV by secondary inoculation, and viraemia kinetics and antibody
      responses were analysed. The marmosets consistently developed high levels of
      viraemia after the secondary inoculation with heterologous DENV serotypes. IgM
      responses were lower compared with primary inoculation responses, whilst IgG
      responses were rapid and high. Neutralizing activities, which possessed serotype
      cross-reactive activities, were detected as early as 4 days after inoculation. In
      addition, infectious viraemia titres were higher when assayed with Fcgamma
      receptor-expressing baby hamster kidney (BHK) cells than when assayed with
      conventional BHK cells, suggesting the presence of infectious virus-antibody
      immune complexes. After secondary infection with heterotypic DENV, the marmosets
      demonstrated viraemia kinetics, IgM and IgG responses, and high levels of
      serotype cross-reactive neutralizing antibody responses, all of which were
      consistent with secondary DENV infection in humans. The results indicate the
      marmoset as a useful animal for studying secondary, as well as primary, DENV
      infection. 

PMID- 24323639
TI  - Neutrophils are needed for an effective immune response against pulmonary rat
      coronavirus infection, but also contribute to pathology.
AB  - Polymorphonuclear neutrophils (PMN) infiltrate the respiratory tract early after
      viral infection and can contribute to both host defence and pathology.
      Coronaviruses are important causes of respiratory tract infections, ranging from
      mild to severe depending on the viral strain. This study evaluated the role of
      PMN during a non-fatal pulmonary coronavirus infection in the natural host. Rat
      coronavirus (RCoV) causes respiratory disease in adult rats, characterized by an
      early PMN response, viral replication and inflammatory lesions in the lungs, mild
      weight loss and effective resolution of infection. To determine their role during
      RCoV infection, PMN were depleted and the effects on disease progression, viral
      replication, inflammatory response and lung pathology were analysed. Compared
      with RCoV infection in control animals, PMN-depleted rats had worsened disease
      with weight loss, clinical signs, mortality and prolonged pulmonary viral
      replication. PMN-depleted animals had fewer macrophages and lymphocytes in the
      respiratory tract, corresponding to lower chemokine levels. Combined with in
      vitro experiments showing that PMN express cytokines and chemokines in response
      to RCoV-infected alveolar epithelial cells, these findings support a role for PMN
      in eliciting an inflammatory response to RCoV infection. Despite their critical
      role in the protection from severe disease, the presence of PMN was correlated
      with haemorrhagic lesions, epithelial barrier permeability and cellular
      inflammation in the lungs. This study demonstrated that while PMN are required
      for an effective antiviral response, they also contribute to lung pathology
      during RCoV infection. 

PMID- 24323640
TI  - Lignin decomposition along an Alpine elevation gradient in relation to
      physicochemical and soil microbial parameters.
AB  - Lignin is an aromatic plant compound that decomposes more slowly than other
      organic matter compounds; however, it was recently shown that lignin could
      decompose as fast as litter bulk carbon in minerals soils. In alpine Histosols,
      where organic matter dynamics is largely unaffected by mineral constituents,
      lignin may be an important part of soil organic matter (SOM). These soils are
      expected to experience alterations in temperature and/or physicochemical
      parameters as a result of global climate change. The effect of these changes on
      lignin dynamics remains to be examined and the importance of lignin as SOM
      compound in these soils evaluated. Here, we investigated the decomposition of
      individual lignin phenols of maize litter incubated for 2 years in-situ in
      Histosols on an Alpine elevation gradient (900, 1300, and 1900 m above sea
      level); to this end, we used the cupric oxide oxidation method and determined the
      phenols' (13) C signature. Maize lignin decomposed faster than bulk maize carbon
      in the first year (86 vs. 78% decomposed); however, after the second year, lignin
      and bulk C decomposition did not differ significantly. Lignin mass loss did not
      correlate with soil temperature after the first year, and even correlated
      negatively at the end of the second year. Lignin mass loss also correlated
      negatively with the remaining maize N at the end of the second year, and we
      interpreted this result as a possible negative influence of nitrogen on lignin
      degradation, although other factors (notably the depletion of easily degradable
      carbon sources) may also have played a role at this stage of decomposition.
      Microbial community composition did not correlate with lignin mass loss, but it
      did so with the lignin degradation indicators (Ac/Al)s and S/V after 2 years of
      decomposition. Progressing substrate decomposition toward the final stages thus
      appears to be linked with microbial community differentiation.

PMID- 24323642
TI  - Loss of NF2/Merlin expression in advanced sporadic colorectal cancer.
AB  - PURPOSE: NF2/Merlin was first identified through its association with
      neurofibromatosis type 2 (NF2). However, accumulating evidence suggests a more
      general involvement in tumorigenesis and, in particular, a broader role in tumor
      suppression. The aim of this study was to examine NF2/Merlin involvement in
      sporadic colorectal cancer. METHODS: This study is the first to examine the role
      of NF2/Merlin in sporadic colorectal cancer through LOH analysis at the NF2 locus
      and mRNA expression analysis via quantitative RT-PCR of total NF2, NF2 isoform I
      and II. In addition, Merlin protein expression was assessed by
      immunohistochemistry and Western blotting. RESULTS: NF2 LOH was detected in 20.0
      % of heterozygous cases and was found to be more frequent in tumors larger than 5
      cm in diameter (p = 0.041) and in tumors with a less differentiated phenotype (p
      = 0.027). No differences were observed in total NF2 and NF2 isoform I/isoform II
      mRNA expression between the tumors and their corresponding normal mucous tissues.
      NF2 isoform II was the most predominant isoform in all samples analyzed. mRNA
      expression levels of total NF2 and isoforms I and II were significantly lower in
      poorly differentiated tumors (p = 0.033, p = 0.036 and p = 0.044, respectively).
      Weak Merlin immunostaining was more frequent in poorly differentiated tumors (p =
      0.034) and tumors classified as Dukes' C (p = 0.023). A distinct pattern of Merin
      phosphorylation was observed in tumors compared to normal mucous tissues.
      CONCLUSION: Our data indicate that NF2/Merlin may serve as a potential target in
      the management of colorectal cancer.

PMID- 24323643
TI  - Topology-dependent swichability of peptide secondary structures in bioconjugates
      with complex architectures.
AB  - Peptide sequences, which exhibit a reversible pH-responsive coil to alpha-helix
      secondary structure transition, are conjugated to polymer precursors to yield
      linear AB and graft ABA peptide-poly(ethylene oxide) conjugates. While the PEO B
      block is comparable, the conjugates differ in topologies of the peptide bearing A
      blocks. The influences of topology on the structure transitions in the peptide
      segments are investigated, comparing linear AB-bioconjugates with graft ABA
      bioconjugates having multiple peptide segments combined in star or pom-pom
      topologies. 

PMID- 24323644
TI  - Cell therapy: exploring new approaches to identify potential stroke treatments.

PMID- 24323641
TI  - Randomized trial of safinamide add-on to levodopa in Parkinson's disease with
      motor fluctuations.
AB  - Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is
      associated with motor fluctuations and dyskinesia. Many patients require add-on
      therapy to improve motor fluctuations without exacerbating dyskinesia. The
      objective of this Phase III, multicenter, double-blind, placebo-controlled,
      parallel-group study was to evaluate the efficacy and safety of safinamide, an
      alpha-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l
      dopa in the treatment of patients with PD and motor fluctuations. Patients were
      randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or
      placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or
      nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary
      endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS)
      Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week
      24, mean +/- SD increases in total on time with no or nontroublesome dyskinesia
      were 1.36 +/- 2.625 hours for safinamide 100 mg/day, 1.37 +/- 2.745 hours for
      safinamide 50 mg/day, and 0.97 +/- 2.375 hours for placebo. Least squares means
      differences in both safinamide groups were significantly higher versus placebo.
      Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in
      both safinamide groups versus placebo. There were no significant between-group
      differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs
      leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to
      l-dopa in patients with PD and motor fluctuations significantly increased total
      on time with no or nontroublesome dyskinesia, decreased off time, and improved
      parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism
      without worsening dyskinesia.

PMID- 24323645
TI  - Orchestrating Recovery: Cell-based Therapy for Stroke.

PMID- 24323646
TI  - Lost in translation? Not!

PMID- 24323647
TI  - Intravascular stem cell transplantation for stroke.
AB  - Stroke is the third leading cause of death and the leading cause of adult
      disability in North America. Emphasis has been placed on developing treatments
      that reduce the devastating long-term impacts of this disease, and preclinical
      research on stem cell therapy has demonstrated promising results. However,
      questions about the optimal cell delivery method and timing of cell
      transplantation are not fully answered. Recent findings suggest that
      intravascular stem cell delivery is a safe and efficacious alternative to
      stereotactic cell injections. It also offers advantages should repeat treatments
      prove beneficial. Recent reports further suggest that intra-arterial injection
      results in a wider distribution of cells throughout the stroked hemisphere with a
      significantly greater cell engraftment compared to intravenous injection. In this
      review, we describe the benefits and potential risks associated with
      intravascular stem cell delivery and compare intra-arterial to intravenous cell
      transplantation methods. We discuss the importance of cell biodistribution and
      timing of transplantation in driving cell survival. We examine current proposed
      mechanisms involved in cell migration and functional recovery and discuss future
      directions for intravascular stem cell therapy research. 

PMID- 24323648
TI  - Intracranial delivery of stem cells.
AB  - The method of delivery of stem cells is a major factor to consider in the design
      of clinical trials of cell therapy. Different methods of delivery will be
      associated with different risks to the patient, and may also be associated with
      different potential for benefit. Current approaches are partly informed by the
      routes selected for study in animal models of focal ischaemia and CNS
      transplantation, but there has been little work comparing the efficacy of
      different routes of administration. Direct intraparenchymal delivery of cells has
      been employed in several preliminary clinical trials, and data on the safety of
      this approach are reviewed. 

PMID- 24323649
TI  - Neural stem cell-based therapy for ischemic stroke.
AB  - Stem cell-based approaches for the treatment of stroke have been the subject of
      intensive research over the past decade. Based on accumulated experimental
      evidence, stem cell-based therapy is a very promising prospect for the
      development of a novel treatment to restore stroke-damaged brain and impaired
      neurological function. Studies performed on experimental animal models of stroke
      employed a variety of stem cell types from diverse sources and have demonstrated
      their ability to replace lost neurons and functionally integrate into the brain,
      modulate inflammation, and stimulate angiogenesis and neurogenesis from an
      endogenous stem cell pool, most likely through trophic actions. A few clinical
      trials in stroke patients using stem cell transplantation have been completed or
      are on-going but the results have not yet proven the effectiveness of the stem
      cell-based approaches. A joint effort of stroke researchers and clinicians is
      needed to further optimize treatment protocols using safe and reproducible stem
      cell sources tested in relevant animal models of stroke and showing substantial
      neurological recovery of stroke-impaired function. 

PMID- 24323650
TI  - Validity of bone marrow stromal cell expansion by animal serum-free medium for
      cell transplantation therapy of cerebral infarct in rats-a serial MRI study.
AB  - This study was aimed to test the hypothesis that human bone marrow stromal cells
      (hBMSC) expanded in fetal calf serum (FCS)-free, platelet lysate (PL)-containing
      medium would retain their capacity of migration, survival, and neural
      differentiation when transplanted into the infarct brain, using serial in vivo
      magnetic resonance imaging (MRI). Cell growth kinetic analysis revealed that
      hBMSC maintain their proliferative activity when cultured either in conventional
      FCS-containing medium or FCS-free, PL-containing medium. Subsequently, hBMSC were
      labeled with a superparamagnetic iron oxide agent and were stereotactically
      transplanted into the ipsilateral striatum of rats at 7 days after permanent
      middle cerebral artery occlusion. Serial MRI performed over 8 weeks revealed that
      they retain their migratory capacity towards the cerebral infarct. Moreover,
      double fluorescence immunohistochemistry also revealed that they preserve their
      capacity of differentiation into the neural cells in the peri-infarct area. The
      hBMSC expanded in the FCS-free, PL-containing medium retain their capacity of
      migration, survival, and differentiation when stereotactically transplanted into
      the infarct brain. The present findings strongly suggest the clinical utility of
      PL as a substitute to expand autologous hBMSC for cerebral infarct in the future.

PMID- 24323651
TI  - Biological Features of Human Bone Marrow Stromal Cells (hBMSC) Cultured with
      Animal Protein-Free Medium-Safety and Efficacy of Clinical Use for
      Neurotransplantation.
AB  - The donor cell culture in animal serum-free medium is quite important for the
      clinical application of cell transplantation therapy. This study was aimed to
      test the hypothesis that the human bone marrow stromal cells (hBMSC) expanded
      with fetal calf serum (FCS)-free, platelet lysate (PL)-containing medium retain
      their biological features favoring central nervous system regeneration. The hBMSC
      were cultured with 5% PL or 10% FCS. Their phenotypes were analyzed with flow
      cytometry, and their production of growth factors was quantified with enzyme
      linked immunosorbent assay. Their capacity of neural differentiation was verified
      by immunocytochemistry. There was no significant difference in morphology and
      cell surface marker between the hBMSC-FCS and hBMSC-PL. Both of them were
      positive for CD44, CD90, CD105, and CD166 and were negative for CD34, CD45, and
      CD271. The production of human brain-derived neurotrophic factor, human
      hepatocyte growth factor, human beta-nerve growth factor, and human platelet
      derived growth factor-BB did not differ between the two groups, although the
      hBMSC-PL produced significantly more amount of TGF-beta1 than the hBMSC-FCS.
      There was no significant difference in their in vitro differentiation into the
      neurons and astrocytes between the two groups. The hBMSC expanded with PL
      containing medium retain their biological capacity of neural differentiation and
      neuroprotection. The PL may be a clinically valuable and safe substitute for FCS
      in expanding the hBMSC for cell therapy. 

PMID- 24323652
TI  - The splenic response to ischemic stroke: what have we learned from rodent models?
AB  - The majority of promising experimental compounds have failed in clinical trials,
      highlighting the need for novel approaches to treat stroke. Much research has
      been devoted to elucidating the signaling pathways involved in delayed
      neuroinflammation that can be targeted at clinically relevant time points. The
      field of stroke research has benefited from experiments characterizing the
      temporal expression profiles of candidate cytokines, chemokines, matrix
      metalloproteinases, and other putative pro-inflammatory molecules. Yet, these
      data have offered only a glimpse into the complex pathological sequelae and have
      not advanced the treatment of neuropathies. Upon recognition that peripheral
      immune cell activation is involved in penumbral expansion, the spleen has emerged
      as a novel target that mediates the peripheral immune response and promotes pro
      inflammatory injury. Although the precise mechanisms have yet to be elucidated,
      accumulated evidence demonstrates that focal cerebral ischemia alters cytokine,
      chemokine, and immune cell profiles in the spleen. Additionally, removal of this
      peripheral lymphoid organ is neuroprotective, and the efficacy of several
      protective therapies has been linked to actions at the level of the spleen.
      Future experiments aimed at identifying the splenic lymphocyte populations that
      respond to ischemic stroke, as well as their signaling mechanisms, are critical
      in developing novel therapies. 

PMID- 24323653
TI  - Androgen receptor overexpression is neuroprotective in experimental stroke.
AB  - Male sex is a known risk factor in human stroke. However, the role of the cognate
      receptor for androgens-the androgen receptor (AR)-in stroke outcome remains
      unclear. Here, we found that AR mRNA is downregulated in the peri-infarct tissue
      of gonadally intact male mice subjected to middle cerebral artery occlusion
      (MCAO) and 6 h reperfusion. We then used genetically engineered mice
      overexpressing AR in brain (AR-Tg) to compare outcomes from MCAO in intact or
      castrated males and to evaluate the neuroprotective role of dihydrotestosterone
      (DHT) replacement in AR-Tg castrates. A further evaluation of AR overexpression
      in ischemic paradigms was performed using rat PC12 cells transfected with human
      AR and treated with oxidative and apoptotic stressors. We then studied the role
      of DHT in cultures overexpressing AR. Our results show (1) ischemia alters the
      expression of AR by decreasing AR mRNA levels, (2) AR overexpression is
      protective in vivo against MCAO in intact and castrated AR-Tg mice and in vitro
      against oxidative and apoptotic stressors in AR-PC12 cells, and (3) DHT does not
      enhance the protection triggered by AR overexpression in AR-Tg castrated mice nor
      in AR-PC12 cells. 

PMID- 24323654
TI  - Granulocyte-colony-stimulating Factor for Acute Ischemic Stroke: A Randomized
      Controlled Trial (STEMTHER).
AB  - Granulocyte-colony-stimulating factor (G-CSF) functions both as a neuroprotectant
      and a stimulator of autologous bone marrow stem cell release. Therefore,
      administration of G-CSF should improve the outcome of stroke. Here, we examine
      the safety of using G-CSF to treat acute ischemic stroke using a randomized
      controlled trial involving 20 adult patients presenting with ischemia in the
      carotid region within 48 h of onset. The experimental group (n = 10) received
      subcutaneous G-CSF injections (10 mg kg(-1) day(-1)) in addition to conventional
      therapy for 5 days. The primary outcome was motor function as measured by the
      modified Rankin Scale 180 days post-stroke. Safety was evaluated according to the
      frequency of hemorrhagic transformation of infarctions and serious adverse
      events. Only six patients in the experimental group completed full course of
      treatment, while four patients (three in the control and one in the experimental
      group) were lost to follow-up. We found the experimental and control groups did
      not differ significantly in either neurological impairment or degree of
      disability/dependence at 180 days post-stroke. We conclude that while adding G
      CSF (10 mg kg(-1) day(-1)) to acute ischemic stroke therapy for 5 days is safe,
      its efficacy remains unproven. 

PMID- 24323655
TI  - Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage
      in Rats.
AB  - It is largely unknown whether prolonged insonation with ultrasound impacts the
      ischemic brain tissue by itself. Our goal was to evaluate safety and the effect
      of high-frequency ultrasound on infarct volume in rats. Thirty-two Long-Evans
      rats with permanent middle cerebral and carotid artery occlusions received either
      2-MHz ultrasound at two levels of insonation power (128 or 10 mW) or no
      ultrasound (controls). We measured cerebral hemorrhage, indirect and direct
      infarct volume as well as edema volume at 24 h. No cerebral hemorrhages were
      detected in all animals. Exposure to low-power (10 mW) ultrasound resulted in a
      significantly decreased indirect infarct volume (p = 0.0039), direct infarct
      volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls.
      High-power (128 mW) ultrasound had no significant effects. An additional
      experiment with India ink showed a greater intravascular penetration of dye into
      ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency,
      low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema
      reduction and possible promotion of microcirculation could be used to facilitate
      drug and nutrient delivery to ischemic areas. 

PMID- 24323656
TI  - Preclinical evaluation of postischemic dehydroascorbic Acid administration in a
      large-animal stroke model.
AB  - Dehydroascorbic acid (DHA), a blood-brain barrier transportable form of ascorbic
      acid, confers robust neuroprotection following murine stroke. In an effort to
      translate this promising neuroprotective strategy into human clinical trial, we
      evaluated postischemic DHA administration in a large-animal stroke model. Thirty
      six adult male baboons were initially randomized to undergo transorbital
      craniectomy to induce transient cerebral artery occlusion and to receive
      postischemic dosing of either 500 mg/kg of DHA or vehicle. Primary outcomes
      included infarct volume, determined by magnetic resonance imaging, as well as
      neurological function evaluated on the day of sacrifice. The midpoint interim
      analysis (n = 9 per cohort) revealed that DHA administration did not
      significantly improve either infarct volume or neurological function. The study
      was terminated after a determination of statistical futility. We were unable to
      confirm a neuroprotective effect for postischemic DHA administration in our large
      animal model using a dosing scheme that was previously successful in rodents.
      Further analysis of the efficacy of DHA administration must thus be undertaken
      prior to clinical translation. 

PMID- 24323657
TI  - Motor function recovery during peripheral nerve multiple regeneration.
AB  - Neuronal functional compensation and multiple regenerating axon sprouting occur
      during peripheral nerve regeneration. Sprouting nerve buds were quantitatively
      maintained and had matured when multiple injured distal nerves were anastomosed
      to smaller number of proximal nerve stumps; this has positive clinical
      significance for proximal stump damage. This study investigated whether sprouting
      axon buds would reinnervate the distal neuromuscular junction and maintain the
      function of the target organ under compensation conditions. The results showed
      that the sprouting axon buds maintained the numbers and morphology of motor end
      plates repaired by a smaller number of proximal nerve stumps, and recovered 80.0%
      tetanic muscle force compared with the normal side. Meanwhile, nerve conduction
      velocity, compound muscle action potential and diameter of muscular fibres
      declined 72.7%, 73.2% and 61.8%, respectively, compared with normal. This
      observation indicates the potential functional reserve of neurons and that it is
      feasible to repair nerve fibre injury through anastomosis of multiple distal
      nerve stumps with a smaller number of proximal nerve stumps, within the limits of
      compensation.

PMID- 24323658
TI  - The efficacy of interventions to reduce adolescent childbearing in low- and
      middle-income countries: a systematic review.
AB  - This study reviews the scope and quality of existing literature regarding the
      interventions to reduce adolescent childbearing in low- and middle-income
      countries and compiles findings concerning their effectiveness. A total of 737
      studies published between 2000 and 2011 were reviewed; 19 were identified as
      meeting eligibility criteria. Studies were included that: evaluated program
      effects on adolescents and young people, either as the primary target population
      or as a subset of a broader target group; evaluated an intervention intended to
      reduce adolescent fertility or generate improvements on a related outcome; and
      reported childbearing-related outcomes. Evidence indicates that a variety of
      interventions may be successful at reducing fertility, including school-based
      programs, health counseling, and cash transfers. An overview of evaluation
      efforts to date is provided, and potential best practices are highlighted.
      Conclusions are that funding for adolescent fertility initiatives should be
      directed toward programs for which a sound evidence base exists, such as cash
      transfers or other interventions that encourage school enrollment, and that
      programs of unknown effectiveness should be conducted in tandem with rigorous
      evaluation. 

PMID- 24323659
TI  - Effect of village midwife program on contraceptive prevalence and method choice
      in Indonesia.
AB  - Indonesia established its Village Midwife Program in 1989 to combat high rates of
      maternal mortality. The program's goals were to address gaps in access to
      reproductive health care for rural women, increase access to and use of family
      planning services, and broaden the mix of available contraceptive methods. In
      this study, we use longitudinal data from the Indonesia Family Life Survey to
      examine the program's effect on contraceptive practice. We find that the program
      did not affect overall contraceptive prevalence but did affect method choice.
      Over time, for women using contraceptives, midwives were associated with
      increased odds of injectable contraceptive use and decreased odds of oral
      contraceptive and implant use. Although the Indonesian government had hoped that
      the Village Midwife Program would channel women into using longer-lasting
      methods, the women's "switching behavior" indicates that the program succeeded in
      providing additional outlets for and promoting the use of injectable
      contraceptives. 

PMID- 24323660
TI  - Managing the double burden: pregnancy and labor-intensive time use in rural
      China, Mexico, and Tanzania.
AB  - Labor-intensive work is often a way of life for women living in rural areas of
      developing countries. The physical exertion involved in such work may result in
      poor health outcomes for mothers and infants when continued through pregnancy.
      Using longitudinal data from China, Mexico, and Tanzania, we examine the
      relationship between pregnancy and four time-use outcomes, measured as hours
      spent in the past week on: (1) housework, (2) caregiving, (3) agricultural work,
      and (4) self-employment or nonagricultural work outside the home. An individual
      fixed-effects approach is adopted to overcome the potential time-invariant woman
      level endogeneity of pregnancy status. With few exceptions, we do not find
      significantly different time-use patterns between pregnant and nonpregnant women.
      The assumption that women decrease labor-intensive work in developing countries
      during pregnancy needs revisiting and may have implications for both women's
      livelihood programming and assistance during childbearing periods. 

PMID- 24323661
TI  - Stakeholder and provider views regarding pericoital contraceptive pills in India
      and Uganda.
AB  - The development of pericoital contraceptive pills is under consideration to
      address unmet need for family planning, especially among women who have
      infrequent sexual intercourse. Pericoital pills, an oral contraceptive taken 24
      hours before or after intercourse, would be a potentially desirable contraceptive
      option because it could provide convenience, discretion, and female control over
      contraceptive use. To gauge receptivity to pericoital contraception, a total of
      49 in-depth interviews and 5 focus group discussions were conducted in India and
      Uganda with family planning providers and stakeholders. In India, the method was
      seen as filling a demonstrated need, based on perceived widespread and/or repeat
      use of emergency contraceptives. In Uganda, where emergency contraception has met
      strong opposition from conservative and religious leaders, respondents were more
      skeptical about the merits of the product. In both settings, using condoms
      consistently and taking oral contraceptives daily present challenges for
      consistent use, thus a new contraceptive method that is easy to use and under
      female control is likely to be appealing.

PMID- 24323662
TI  - Ethiopia: an emerging family planning success story.
AB  - From 1990 to 2011, contraceptive use in Ethiopia increased ninefold and the total
      fertility rate fell from 7.0 to 4.8. These are two dramatic illustrations of a
      family planning success story that has emerged over the last two decades and is
      still emerging. What are the main elements of this success? We posit that the
      four most significant factors are: political will, generous donor support,
      nongovernmental and public-private partnerships, and the government's
      establishment of a network of health extension workers. In this study, we look at
      these factors and how their interaction increased the proportion of women having
      both the desire to use and ability to access contraceptives. Also highlighted are
      some of the key lessons learned in Ethiopia that are relevant to other African
      countries interested in emulating the country's success. 

PMID- 24323663
TI  - Honduras 2011-12.

PMID- 24323664
TI  - Mozambique 2011.

PMID- 24323666
TI  - A review of peer review by peers.

PMID- 24323667
TI  - Results of percutaneous closure of patent foramen ovale with the GORE((r)) septal
      occluder.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the
      GORE((r)) Septal Occluder (GSO) at 1-, 6-, and 12-month follow-up in patients
      with a clinical indication for patent foramen ovale (PFO) closure. BACKGROUND:
      Limited data are available regarding the safety and efficacy of the GSO for PFO
      closure. METHODS: Sixty consecutive patients with an embolic event, migraine, or
      risk of decompression sickness were enrolled. Transesophageal or transthoracic
      echocardiography and clinical follow-up were performed at 1, 6 and 12 months
      after implantation. All patients received 100 mg aspirin and 75 mg clopidogrel
      for 6 months. RESULTS: Procedures were technically successful in 98.3% (59/60).
      In one case, the anterior interatrial septal rim proved too short to allow safe
      GSO implantation and, instead, a different occluder was implanted. One patient
      developed transient neurological symptoms during the procedure without evidence
      for a stroke by magnetic resonance imaging. At 6-month follow-up, the closure
      rate was 86.6% (52/60). The complete closure rate after 1 year was 93.3% (56/60).
      Stroke, thrombus formation and atrial fibrillation (AF)/flutter occurred in 1
      (1.7%), 1 (1.7%), and 5 (8.3%) patients, respectively. CONCLUSION: PFO closure
      with the GSO is accompanied by a high technical success rate and closure rates
      similar to other currently used devices. The incidence of AF was higher than
      reported with most other devices. This may be a chance finding but warrants
      further investigation in larger trials.

PMID- 24323668
TI  - A multivariate multilevel Gaussian model with a mixed effects structure in the
      mean and covariance part.
AB  - A traditional Gaussian hierarchical model assumes a nested multilevel structure
      for the mean and a constant variance at each level. We propose a Bayesian
      multivariate multilevel factor model that assumes a multilevel structure for both
      the mean and the covariance matrix. That is, in addition to a multilevel
      structure for the mean we also assume that the covariance matrix depends on
      covariates and random effects. This allows to explore whether the covariance
      structure depends on the values of the higher levels and as such models
      heterogeneity in the variances and correlation structure of the multivariate
      outcome across the higher level values. The approach is applied to the three
      dimensional vector of burnout measurements collected on nurses in a large
      European study to answer the research question whether the covariance matrix of
      the outcomes depends on recorded system-level features in the organization of
      nursing care, but also on not-recorded factors that vary with countries,
      hospitals, and nursing units. Simulations illustrate the performance of our
      modeling approach.

PMID- 24323669
TI  - Preparation of an autologous heart valve with a stent (stent-biovalve) using the
      stent eversion method.
AB  - We designed a novel method for constructing an autologous heart valve with a
      stent, called a stent-biovalve. In constructing completely autologous heart
      valves, named biovalves, which used in-body tissue architecture technology,
      tissues for leaflets were formed via ingrowths into narrow apertures in the
      preparation molds, frequently leading to delayed or incomplete biovalve
      preparation. In this technique, self-expandable nitinol stents after everting
      were mounted on an acrylic column-shaped part and partially covered with an
      acrylic cylinder-shaped part with three slits. This assembled mold was placed
      into subcutaneous abdominal pouches in beagles or goats for 4 weeks. Upon
      removing the acrylic parts after harvesting and trimming of capsulated tissues, a
      tubular hollow structure with three pocket-flaps of membranous tissue rigidly
      fixed to the stent's outer surface was obtained. Then, the stent was turned
      inside out to the original form, thus moving the pocket-flaps from outside to the
      inside. Stent-biovalves with a sufficient coaptation area were thus obtained with
      little tissue damage in all cases. The valve opened smoothly, and high aperture
      ratio was noted. This novel technique was thus highly effective in constructing a
      robust, completely autologous stent-biovalve with adequate valve function.

PMID- 24323670
TI  - Current management of acute scaphoid fractures: a review.
AB  - The aim of this review was to present currently available evidence on the
      management of acute scaphoid fractures. Acute scaphoid fractures are usually
      diagnosed by a combination of history, physical examination, and radiography.
      However, in many patients scaphoid fractures are still missed. Thus, the general
      trend is to over-treat patients with a suspicion of scaphoid fracture. Many
      aspects of scaphoid fracture management are still controversial and different
      institutions vary in their approach. 

PMID- 24323671
TI  - Obsessive-compulsive disorder in general hospital outpatients: prevalence,
      correlates, and comorbidity in Lanzhou, China.
AB  - INTRODUCTION: The prevalence of obsessive-compulsive disorder (OCD), risk
      factors, and comorbidity rates of Chinese outpatients in Lanzhou general
      hospitals are unknown. METHOD: The prevalence rate of OCD was estimated in a
      representative sample of outpatients in three classes of general hospitals in
      Lanzhou, China. The rate of OCD within the sample, which was composed of 1,576
      individuals aged 16 years or older, was assessed using the World Health
      Organization Composite International Diagnostic Interview Version 3.0. RESULTS:
      The weighted prevalence of OCD were 4.31% (lifetime), 2.86% (12-month), and 1.97%
      (30-day). Multivariate logistic regression identified the following independent
      predictors of having lifetime OCD: having a higher level of education, being
      unemployed, an internal medicine outpatient, a female, 16-35 years old,
      divorced/widowed/separated, and having a low family income. OCD had a significant
      comorbid association with neuroses, based on the International Statistical
      Classification of Diseases and Related Health Problems-10th Revision. DISCUSSION:
      These findings show a lower prevalence rate of OCD in Lanzhou general hospitals
      than that reported for some specialized outpatient clinics in Western countries.
      Further investigations are required to explore the relationships between OCD and
      the risk factors identified in the current study. Resolving methodological
      problems may lead to more accurate prevalence estimates in future epidemiological
      studies. Our findings suggest that there is an urgent need to improve the ability
      of clinicians to detect OCD in outpatients.

PMID- 24323673
TI  - Early top-down control over saccadic target selection: Evidence from a systematic
      salience difference manipulation.
AB  - Previous research on the contribution of top-down control to saccadic target
      selection has suggested that eye movements, especially short-latency saccades,
      are primarily salience driven. The present study was designed to systematically
      examine top-down influences as a function of time and relative salience
      difference between target and distractor. Observers performed a saccadic
      selection task, requiring them to make an eye movement to an orientation-defined
      target, while ignoring a color-defined distractor. The salience of the distractor
      was varied (five levels), permitting the percentage of target and distractor
      fixations to be analyzed as a function of the salience difference between the
      target and distractor. This analysis revealed the same pattern of results for
      both the overall and the short-latency saccades: When the target and distractor
      were of comparable salience, the vast majority of saccades went directly to the
      target; even distractors somewhat more salient than the target led to
      significantly fewer distractor, as compared with target, fixations. To quantify
      the amount of top-down control applied, we estimated the point of equal selection
      probability for the target and distractor. Analyses of these estimates revealed
      that, to be selected with equal probability to the target, a distractor had to
      have a considerably greater bottom-up salience, as compared with the target. This
      difference suggests a strong contribution of top-down control to saccadic target
      selection-even for the earliest saccades.

PMID- 24323674
TI  - Rigidity loss of protein macromolecule induced by force--effective field theory.
AB  - In the framework of the effective field theory for the order parameter, which
      characterizes the degree of deviating the protein globule structure from its
      native state, the phase transition of the protein macromolecule from the elastic
      state into the plastic one under its mechanical stretching is considered. Elastic
      properties of a protein are studied as a function of the applied force,
      temperature, and the mean coordination number of the protein "network."

PMID- 24323672
TI  - AKAP150 contributes to enhanced vascular tone by facilitating large-conductance
      Ca2+-activated K+ channel remodeling in hyperglycemia and diabetes mellitus.
AB  - RATIONALE: Increased contractility of arterial myocytes and enhanced vascular
      tone during hyperglycemia and diabetes mellitus may arise from impaired large
      conductance Ca(2+)-activated K(+) (BKCa) channel function. The scaffolding
      protein A-kinase anchoring protein 150 (AKAP150) is a key regulator of
      calcineurin (CaN), a phosphatase known to modulate the expression of the
      regulatory BKCa beta1 subunit. Whether AKAP150 mediates BKCa channel suppression
      during hyperglycemia and diabetes mellitus is unknown. OBJECTIVE: To test the
      hypothesis that AKAP150-dependent CaN signaling mediates BKCa beta1
      downregulation and impaired vascular BKCa channel function during hyperglycemia
      and diabetes mellitus. METHODS AND RESULTS: We found that AKAP150 is an important
      determinant of BKCa channel remodeling, CaN/nuclear factor of activated T-cells
      c3 (NFATc3) activation, and resistance artery constriction in hyperglycemic
      animals on high-fat diet. Genetic ablation of AKAP150 protected against these
      alterations, including augmented vasoconstriction. d-glucose-dependent
      suppression of BKCa channel beta1 subunits required Ca(2+) influx via voltage
      gated L-type Ca(2+) channels and mobilization of a CaN/NFATc3 signaling pathway.
      Remarkably, high-fat diet mice expressing a mutant AKAP150 unable to anchor CaN
      resisted activation of NFATc3 and downregulation of BKCa beta1 subunits and
      attenuated high-fat diet-induced elevation in arterial blood pressure.
      CONCLUSIONS: Our results support a model whereby subcellular anchoring of CaN by
      AKAP150 is a key molecular determinant of vascular BKCa channel remodeling, which
      contributes to vasoconstriction during diabetes mellitus.

PMID- 24323675
TI  - Peritoneal cell sheets composed of mesothelial cells and fibroblasts prevent
      intra-abdominal adhesion formation in a rat model.
AB  - Postoperative intra-abdominal adhesions remain an unsolved problem despite
      significant progress in the surgical procedures themselves. They often lead to
      small-bowel obstruction, chronic abdominal and pelvic pain, as well as female
      infertility. The loss of mesothelial cells and several components of the
      inflammatory system following injury to the peritoneum results in fibrin
      formation and angiogenesis. The remaining fibrin matrix and angiogenesis lead to
      replacement by fibroblasts and fibrous band formation. The aim of this study was
      to develop a new therapeutic method of preventing intra-abdominal adhesions. We
      fabricated transplantable peritoneal cell sheets from the rat peritoneum by cell
      sheet engineering using a temperature-responsive culture system. The peritoneal
      cell sheets developed were composed of an upper monolayer of mesothelial cells
      and underlying multilayered fibroblasts, similar to the peritoneum in vivo.
      Transplantation of peritoneal cell sheets prevented tissue adhesion, fibrin
      deposition and angiogenesis, and, moreover, lymphangiogenesis and macrophage
      infiltration in a rat caecum cauterization adhesion model. Copyright (c) 2013
      John Wiley & Sons, Ltd.

PMID- 24323676
TI  - Combination of a photosystem 1-based photocathode and a photosystem 2-based
      photoanode to a Z-scheme mimic for biophotovoltaic applications.

PMID- 24323677
TI  - Translational research in neurotrauma: novel mechanisms and emerging therapies.

PMID- 24323678
TI  - State of the Art in Cerebral Trauma: A Neurosurgeon's Perspective.

PMID- 24323679
TI  - The incomplete picture of incomplete spinal cord injury.

PMID- 24323680
TI  - A brief history of behavioral assessment following experimental traumatic brain
      injury in juveniles.
AB  - This review focuses on assessment of behavioral outcomes following traumatic
      brain injury in juvenile animal models. In the 15 years since the first
      publication in this field, the majority of studies have used rats roughly
      equivalent to human toddlers in terms of brain development. Few studies have
      tested ages closer to human neonates, and fewer have assessed ages closer to
      human adolescents. Closed head impact has been the most commonly used model,
      causing relatively consistent motor and cognitive deficits. Additionally, closed
      head impacts of a more severe nature have generally led to behavioral deficits of
      a more severe nature. Impact models (both closed and open skull) have produced
      more severe deficits in younger animals than in older animals, similar to
      patterns observed in juvenile humans with traumatic brain injury. In contrast,
      the fluid percussion model has produced relatively subtle deficits that did not
      get worse with a more severe injury and were worse for older animals than younger
      animals. Most of the studies have looked at relatively short postinjury time
      points, and none so far have assessed behavior in old adult animals injured as
      juveniles. The review ends with a discussion of possible directions for future
      animal research into juvenile traumatic brain injury. 

PMID- 24323681
TI  - Protein biomarkers for traumatic and ischemic brain injury: from bench to
      bedside.
AB  - Stroke is the second leading cause of death worldwide and the third leading cause
      of death in the USA. A clinically useful biomarker for the diagnosis of stroke
      does not currently exist. Biomarkers could improve stroke care by allowing early
      diagnosis by non-expert clinical providers, serial monitoring of patients, and
      rapid assessment of severity of brain injury. With the introduction of highly
      advanced multidimensional separation techniques coupled with high throughput
      genomics/proteomics platforms, several components of the pathophysiological and
      biochemical pathways have been elucidated in the areas of brain trauma. A major
      outcome of these approaches is the discovery of biomarkers that would have
      important applications in diagnosis, prognosis, and even development of
      experimental neuroprotective drugs that have been used in different paradigms of
      brain injury. In this paper, we reviewed the recent advances of current and novel
      brain injury protein biomarkers and their utilities in different models of brain
      injury with an emphasis on stroke, an area that has been understudied. This will
      include the utility of neuroproteomics/neurosystems biology analysis as a novel
      discipline leading to the identification of novel biomarkers that can reach the
      pipeline of bench side. Additionally, an outline of biomarker-based management of
      traumatic brain injury and stroke patient assessments of therapeutic
      interventions has been included. Finally, comparison of current biomarker
      occurrence between preclinical models and biomarker data from human clinical
      studies for stroke has been summarized. 

PMID- 24323682
TI  - Does Ischemia Contribute to Energy Failure in Severe TBI?
AB  - Ischemia has long been regarded as a cause of secondary brain injury following
      severe traumatic brain injury (TBI). This manuscript will present the viewpoint
      that, except for cases of extremely low cerebral perfusion pressure, efforts to
      establish the presence of ischemia in TBI patients using a variety of techniques
      have been inconclusive. Early studies found that cerebral blood flow (CBF) was
      low in acute TBI patients, suggesting ischemia. However, CBF can be low but
      adequate to meet tissue energy needs in the presence of a low cerebral metabolic
      rate; so in such situations, measurement of blood flow, metabolism and oxygen
      update are necessary to detect ischemia. There is little doubt that ischemia
      occurs in severe TBI when cerebral oxygen delivery is markedly compromised,
      however, the role of ischemia outside of this extreme remains unresolved at
      present. Early after injury, global blood flow, metabolism, and oxygen extraction
      are reduced suggesting suppressed metabolism rather than active ischemia.
      Multiple factors including over excitation, calcium influx, and oxidative stress,
      and hyperacute ischemia may contribute to this process, but evidence of ongoing
      ischemic injury is mixed. Data from microdialysis probes provide differing
      results depending on what is measured and how it is interpreted and yield results
      that are inconsistent with brain tissue oxygen tension data. PET studies,
      depending on how they are analyzed and the thresholds used, indicate either no
      ischemia or a small volume of ischemic brain. 

PMID- 24323685
TI  - A Critical Re-Examination of the Intraluminal Filament MCAO Model: Impact of
      External Carotid Artery Transection.
AB  - The intraluminal filament procedure is the most common model of middle cerebral
      artery occlusion (MCAO). However, consequences of subtle variations in surgical
      technique on behavioral outcome measures have not been sufficiently explored,
      which is the aim of this study. Rats randomly received one of three types of
      transient MCAO (60 min) surgeries. The first transected the external carotid
      artery (ECA) for filament insertion. The other two inserted the filament in the
      carotid artery (CA), and after reperfusion, the CA was either ligated or blood
      flow restored. All animals, including shams and naive controls, were monitored
      with behavioral tests for 90 days. Lesion size and NeuN + cells in the striatum
      were comparable among MCAO groups. However, rats with ECA transection were
      consistently lighter than rats with permanent CA ligation, which were lighter
      than rats with CA reperfusion. Furthermore, rats with ECA transection exhibited
      the poorest lick efficiency and the greatest impairments in sensorimotor tasks.
      This study is the first to systematically evaluate the role of ECA transection on
      functional and morbidity outcomes. Behavioral impairments attributable to the
      surgical procedure were observed. This confounds studies and is an important
      issue that needs to be considered when using the intraluminal filament model. 

PMID- 24323683
TI  - Vascular Pathology as a Potential Therapeutic Target in SCI.
AB  - Acute traumatic spinal cord injury (SCI) is characterized by a progressive
      secondary degeneration which exacerbates the loss of penumbral tissue and
      neurological function. Here, we first provide an overview of the known
      pathophysiological mechanisms involving injured microvasculature and molecular
      regulators that contribute to the loss and dysfunction of existing and new blood
      vessels. We also highlight the differences between traumatic and ischemic
      injuries which may yield clues as to the more devastating nature of traumatic
      injuries, possibly involving toxicity associated with hemorrhage. We also discuss
      known species differences with implications for choosing models, their relevance
      and utility to translate new treatments towards the clinic. Throughout this
      review, we highlight the potential opportunities and proof-of-concept
      experimental studies for targeting therapies to endothelial cell-specific
      responses. Lastly, we comment on the need for vascular mechanisms to be included
      in drug development and non-invasive diagnostics such as serum and cerebrospinal
      fluid biomarkers and imaging of spinal cord pathology. 

PMID- 24323686
TI  - A stimuli-responsive nanogel-based sensitive and selective fluorescent sensor for
      Cr(3+) with thermo-induced tunable detection sensitivity.
AB  - Stimuli-responsive poly(N-isopropylacrylamide) nanogel with covalently labeled
      rhodamine B urea derivatives (P(NIPAM-co-RhBUA)) is utilized as a sensitive
      fluorescent probe for Cr(3+) in aqueous solution, and its thermo-induced tunable
      detection capacity is investigated. At 20  degrees C, non-fluorescent nanogel can
      selectively bind with Cr(3+) over some other metal ions, leading to prominent
      fluorescence OFF-ON switching due to the recognition of RhBUA with Cr(3+) . Upon
      heating above the phase transition temperature, enhanced fluorescence intensity
      is observed (~61-fold increase at 45  degrees C) for the nanogel in the presence
      of Cr(3+) , accompanied with an improved detection sensitivity, which suggest
      that hydrophobic microenvironment generated in the collapsed nanogel plays an
      active role for their detection performance. 

PMID- 24323684
TI  - Therapeutic targeting of astrocytes after traumatic brain injury.
AB  - Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity
      worldwide. A major focus of preclinical research has focused on understanding the
      mechanisms of acute cell death after TBI; however, translation of these findings
      into the clinic has failed to improve long-term patient outcomes. Recent work
      suggests astrocytes, the predominant cell type within the human brain, may
      actively contribute to neurological demise by exacerbating secondary brain injury
      after TBI. Along these lines, astrocytes may promote neuroinflammation, increase
      the development of cerebral edema, and contribute to elevated intracranial
      pressure after brain injury. The primary goal of this mini-review is to summarize
      the growing body of literature that suggests reactive astrocytes influence the
      brain response to TBI. To maintain focus, we will limit our discussion to the
      mechanisms of cerebral edema. 

PMID- 24323687
TI  - Does preoperative American Society of Anesthesiologists score relate to
      complications after total shoulder arthroplasty?
AB  - BACKGROUND: For hip and knee arthroplasties, an American Society of
      Anesthesiologists (ASA) score greater than 2 is associated with an increased risk
      of medical and surgical complications. No study, to our knowledge, has evaluated
      this relationship for total shoulder arthroplasty (TSA) or reverse total shoulder
      arthroplasty (reverse TSA). QUESTIONS/PURPOSES: We aimed to assess the
      relationship between the ASA score and (1) surgical complications, (2) medical
      complications, and (3) hospitalization length after TSA, reverse TSA, and
      revision arthroplasty. METHODS: We retrospectively analyzed all patients who had
      undergone TSAs, reverse TSAs, or revision arthroplasties by the senior author
      (EGM) from November 1999 through July 2011 who had at least 6 months' followup.
      Of the 485 procedures, 452 (93.2%) met the inclusion criteria. Data were
      collected on patient demographics, comorbidities, hospitalization length, and
      short-term (<= 6 months) medical and surgical complications. Logistic regression
      analysis modeled the risk of having postoperative complications develop as a
      function of the ASA score. RESULTS: Patients with an ASA score greater than 2 had
      a greater risk of having a surgical complication develop (p < 0.001; OR, 2.27;
      95% CI, 1.36-3.70) and three times the risk of prosthesis failure (ie, component
      dislocation, component loosening, and hardware failure) (p < 0.001; OR, 3.23; 95%
      CI, 1.54-6.67). Higher ASA scores were associated with prolonged length of
      hospitalization (effect size 0.46, p < 0.001), but not medical complications.
      CONCLUSIONS: ASA score is associated with surgical, but not medical,
      complications after TSA and reverse TSA. The ASA score could be used for risk
      assessment and preoperative counseling. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24323688
TI  - Effects of external rotation on anteroposterior translations in the shoulder: a
      pilot study.
AB  - BACKGROUND: Using physical examination to make the diagnosis of shoulder
      instability can be difficult, because typical examination maneuvers are
      qualitative, difficult to standardize, and not reproducible. Measuring shoulder
      translation is especially difficult, which is a particular problem, because
      measuring it inaccurately may result in improper treatment of instability.
      QUESTIONS/PURPOSES: The objective of this study was to use a magnetic motion
      tracking system to quantify the effects of external rotation of the abducted
      shoulder on a simulated simple translation test in healthy subjects.
      Specifically, we hypothesized that (1) increasing external rotation of the
      abducted shoulder would result in decreasing translation; (2) intraobserver
      repeatability would be less than 2 mm at all external rotation positions; and (3)
      mean side-to-side differences would be less than 2 mm at all external rotation
      positions. METHODS: The intraobserver repeatability and side-to-side differences
      of AP translation were quantified with a noninvasive magnetic motion tracking
      system and automated data analysis routine in nine healthy subjects at four
      positions of external rotation with the arm abducted. A shoulder positioning
      apparatus was used to maintain the desired arm position. RESULTS: No differences
      in translations between the positions of external rotation were found (p = 0.48).
      Intraobserver repeatability was 1.1 mm (SD, 0.8 mm) and mean side-to-side
      differences were small: 2.7 mm (SD, 2.8 mm), 2.8 mm (SD, 1.8 mm), 2.5 mm (SD, 1.8
      mm), and 4.0 mm (SD, 2.6 mm) at 0 degrees , 20 degrees , 40 degrees , and 60
      degrees  of external rotation, respectively. CONCLUSIONS: The intraobserver
      repeatability was strong and the side-to-side differences in translation were
      small with the magnetic motion tracking system, which is encouraging for
      development of an improved quantitative test to assess shoulder translation for
      fast and low-cost diagnosis of shoulder instability. CLINICAL RELEVANCE:
      Clinicians may not have to position the contralateral, normal, abducted shoulder
      in precisely the same position of external rotation as the injured shoulder while
      performing side-to-side comparisons.

PMID- 24323689
TI  - Adverse reactions of artificial bone graft substitutes: lessons learned from
      using tricalcium phosphate geneX (r).

PMID- 24323690
TI  - Reply to the Letter to the Editor: Adverse reactions of artificial bone graft
      substitutes: lessons learned from using tricalcium phosphate geneX (r).

PMID- 24323691
TI  - Child abuse in the context of intimate partner violence against women: the impact
      of women's depressive and posttraumatic stress symptoms on maternal behavior.
AB  - Intimate male partner violence against women has been recognized as an important
      public health problem, with a high impact on women's mental health, including
      depressive and posttraumatic stress disorder (PTSD) symptoms. However, fathers
      who have been involved in intimate partner violence (IPV) have an increased
      probability of being violent toward their children. The aim of this study was to
      assess the relation between the mental health status of abused women, their
      partner's violence toward the children, and their maternal behavior. 

PMID- 24323692
TI  - Social reactions to sexual assault disclosure and problem drinking: mediating
      effects of perceived control and PTSD.
AB  - Sexual assault survivors receive various positive and negative social reactions
      to assault disclosures, yet little is known about mechanisms linking these social
      reactions to posttraumatic stress disorder (PTSD) symptoms and problem drinking.
      Data from a large, diverse sample of women who had experienced adult sexual
      assault were analyzed with structural equation modeling to test a theoretical
      model of the relationships between specific negative social reactions (e.g.,
      controlling, infantilizing) and positive reactions (e.g., tangible support),
      perceived control over recovery, PTSD, and drinking outcomes (N = 1,863). A model
      disaggregating controlling reactions from infantilizing reactions showed that
      infantilizing reactions in particular related to less perceived control, which in
      turn was related to more PTSD and problem drinking, whereas controlling reactions
      were not related to perceived control, PTSD, or problem drinking. Tangible
      support was related to increased perceived control over recovery, yet it was not
      protective against PTSD or problem drinking. Finally, PTSD and drinking to cope
      fully mediated the effect of perceived control on problem drinking. Implications
      for practice and suggestions for future research are discussed. 

PMID- 24323693
TI  - Relationship of trauma exposure and substance abuse to self-reported violence
      among men and women in substance abuse treatment.
AB  - Past research showed a relationship between substance abuse and aggression and
      past trauma and aggression. The nature of the relationships between substance
      use, trauma, and aggression is inconclusive. The current research hypothesized
      greater aggression among those with a history of substance abuse and trauma
      compared with those without such a history and an additive relationship between
      substance abuse and trauma on aggression. Participants were 615 individuals in a
      substance abuse treatment program for individuals under criminal justice
      supervision. Data were collected from face-to-face interviews and self-report
      measures. Univariate and multivariate analyses assessed the relationships among
      substance use, trauma, and aggression. Participants with a history of trauma and
      regular substance use reported the highest rates of homicidal ideation, problem
      behaviors, and person offenses. Participants in this group also reported greater
      desire for help managing their stress and tension, dealing with problems in their
      intimate relationships, developing healthier relationships in general, and
      learning prosocial approaches to express their feelings. Substance abusing
      participants who experienced trauma reported more externalizing behaviors and a
      greater desire for coping- and social-skills training than participants who
      abused substances but did not report a history of trauma. This suggests that
      participants in substance abuse treatment programs may have improved outcomes
      with the addition of components to address these issues. 

PMID- 24323694
TI  - The relationship between victimization and mental health functioning in homeless
      youth and adults.
AB  - This study examined the relationship between victimization and mental health
      functioning in homeless individuals. Homeless populations experience higher
      levels of victimization than the general population, which in turn have a
      detrimental effect on their mental health. A sample of 304 homeless adults and
      youth completed one-on-one interviews, answering questions on mental health, past
      victimization, and recent victimization experiences. A hierarchical linear
      regression showed that experiences of childhood sexual abuse predicted lower
      mental health functioning after controlling for the sex and age of individuals.
      The study findings are applicable to current support programs for victims in the
      homeless population and are relevant to future research on homelessness and
      victimization. 

PMID- 24323695
TI  - Victims' barriers to discussing domestic violence in clinical consultations: a
      qualitative enquiry.
AB  - Victims of domestic violence frequently attend health care facilities. In many
      cases, their abusive experience is neither disclosed nor discussed during
      clinical consultations. This study examined the barriers faced by women when
      discussing abuse with health care providers, specifically in cases involving
      Malaysian women with a history of domestic violence. A qualitative study using in
      depth interviews was conducted with 10 women with a history of domestic violence
      residing at a shelter. Purposive sampling was conducted until data saturation.
      Using the grounded theory approach of analysis, themes that emerged from these
      interviews were then further analyzed to examine the barriers faced by these
      women. Women who experienced domestic violence faced multiple barriers while
      discussing their accounts of abuse with others. Values placed on the privacy of
      domestic violence; upholding the traditional gender roles; preserving the family
      unity; minimizing the abuse, the feeling of shame, self-blame; and fearing their
      abuser generally create internal barriers when discussing their encounters of
      abuse with health care providers. The perceived unknown role of health care
      professionals when dealing with patients experiencing domestic violence as well
      as the previous negative experiences in clinical consultations acted as external
      barriers for discussing abuse with health care providers. Women with domestic
      violence experiences faced internal and external barriers to discussing their
      abuse during clinical consultations. Physicians and health care providers must
      consider domestic violence in consultations with female patients. A good doctor
      patient relationship that encompasses empathy, confidence, trust, support,
      assurance, confidentiality, and guidance can help patients with abusive
      backgrounds overcome these barriers, leading to the disclosure and discussion of
      their abusive encounters. Proper education, guidelines, and support for health
      care providers are required to help them assist women with histories of domestic
      violence. 

PMID- 24323696
TI  - Cardiac surgery in Germany during 2012: a report on behalf of the German Society
      for Thoracic and Cardiovascular Surgery.
AB  - On the basis of a voluntary registry of the German Society for Thoracic and
      Cardiovascular Surgery (GSTCVS), data of all cardiac surgical procedures
      performed in 79 German cardiac surgical units during the year 2012 are presented.
      In 2012, a total of 98,792 cardiac surgical procedures (ICD and pacemaker
      procedures excluded) were submitted to the registry. More than 13.8% of the
      patients were older than 80 years, which is a further increase in comparison to
      previous years. In-hospital mortality in 42,060 isolated coronary artery bypass
      grafting procedures (84.6% on-pump and 15.4% off-pump) was 2.9%. In 28,521
      isolated valve procedures (including 6,804 catheter-based procedures), an in
      hospital mortality of 4.8% was observed. This long-lasting registry of the GSTCVS
      will continue to be an important tool for quality control and voluntary public
      reporting by illustrating current facts and developments of cardiac surgery in
      Germany. 

PMID- 24323697
TI  - Theodor Waitz on psychic unity.
AB  - The tolerant stance on 'race' by prominent Enlightenment figures was followed in
      the 19th century by a powerful wave of biological racism. Many of its proponents
      took the view that human 'races' constitute separate species, and that most non
      white ones are of inferior mentality. An early opponent of this claim was James
      Cowles Prichard, who used mainly missionary reports in seeking to refute it. Far
      more extensive work was undertaken by the Herbartian psychologist Theodor Waitz,
      who collected ethnographic material from all over the world. It was published in
      six volumes - the last two after his death by his former student Georg Gerland.
      Waitz aim was to demonstrate the 'psychic unity' of mankind. Initially extracts
      from the volume on African peoples are presented in order to show how he dealt
      with his material. The main focus is on his first volume entitled Introduction to
      Anthropology, in which he elaborates his general thesis. In it Waitz maintains,
      against the biological racists, that mankind is a single species. Furthermore he
      discusses the changes from savagery to civilization, attributing them to a
      combination of geography and history. He was followed by Adolf Bastian who,
      unlike Waitz, was a great traveller with personal experience of peoples all over
      the globe. Both firmly believed in the psychic unity of mankind, but Bastian's
      approach to psychology was very different. 

PMID- 24323698
TI  - Comparison of drug-eluting and bare metal stents in large coronary arteries:
      findings from the NHLBI dynamic registry.
AB  - OBJECTIVES: This study sought to evaluate the safety and effectiveness of drug
      eluting stents (DES) compared to bare-metal stents (BMS) for patients with large
      coronary vessels. BACKGROUND: Randomized trials have demonstrated that DES reduce
      the risk of target vessel revascularization (TVR) compared to BMS. This benefit
      is less pronounced as artery diameter increases. Whether DES are superior to BMS
      for larger coronary arteries in the setting of routine clinical practice is
      unknown. METHODS: We analyzed data from 869 patients undergoing de novo lesion
      PCI with reference vessel diameter greater than or equal to 3.5 mm in the NHLBI
      Dynamic Registry according to whether they were treated with DES or BMS. Patients
      were followed for 3 years for the occurrence of cardiovascular events. RESULTS:
      At 3-year follow-up, rates of TVR at 3 years were similar and low in both groups
      (4.4% vs. 3.7%, P = 0.62). After adjustment for differences in baseline
      characteristics, the adjusted hazard ratio for 3-year MI for DES was 1.85 (95% CI
      0.93-3.7, P = 0.08), for TVR at 3 years 1.14 (95% CI 0.52-2.49, P = 0.75) and for
      mortality 0.89 (95%CI 0.49-1.62, P = 0.71). CONCLUSIONS: In our study of the
      unrestricted use of DES for patients with lesions in larger diameter coronary
      arteries, first generation DES did not reduce 3-year risk of TVR. Our findings do
      not support the preferred use of DES over BMS for patients with lesions located
      in arteries >3.5 mm. It is unknown whether secondary generation DES can offer
      better outcome compared to BMS in large coronary vessels. Further study on this
      issue is warranted.

PMID- 24323700
TI  - A Tribute to the Philadelphia Lipid Group on the Occasion of Their Retirement.
AB  - none.

PMID- 24323699
TI  - RP-HPLC-fluorescence analysis of aliphatic aldehydes: application to aldehyde
      generating enzymes HACL1 and SGPL1.
AB  - Long-chain aldehydes are commonly produced in various processes, such as
      peroxisomal alpha-oxidation of long-chain 3-methyl-branched and 2-hydroxy fatty
      acids and microsomal breakdown of phosphorylated sphingoid bases. The enzymes
      involved in the aldehyde-generating steps of these processes are 2-hydroxyacyl
      CoA lyase (HACL1) and sphingosine-1-phosphate lyase (SGPL1), respectively. In the
      present work, nonradioactive assays for these enzymes were developed employing
      the Hantzsch reaction. Tridecanal (C13-al) and heptadecanal (C17-al) were
      selected as model compounds and cyclohexane-1,3-dione as 1,3-diketone, and the
      fluorescent derivatives were analyzed by reversed phase (RP)-HPLC. Assay mixture
      composition, as well as pH and heating, were optimized for C13-al and C17-al.
      Under optimized conditions, these aldehydes could be quantified in picomolar
      range and different long-chain aldehyde derivatives were well resolved with a
      linear gradient elution by RP-HPLC. Aldehydes generated by recombinant enzymes
      could easily be detected via this method. Moreover, the assay allowed to document
      activity or deficiency in tissue homogenates and fibroblast lysates without an
      extraction step. In conclusion, a simple, quick, and cheap assay for the study of
      HACL1 and SGPL1 activities was developed, without relying on expensive mass
      spectrometric detectors or radioactive substrates. 

PMID- 24323701
TI  - Validation of the fetal alcohol spectrum disorder (FASD) 4-Digit Diagnostic Code.
AB  - BACKGROUND: The fetal alcohol spectrum disorder (FASD) 4-Digit Diagnostic Code
      has been used by interdisciplinary diagnostic teams worldwide for 17 years. It
      was created to improve the ease, accuracy, and reproducibility of diagnoses
      across the full spectrum of FASD. Over the years, a number of FAS/D diagnostic
      guidelines have been proposed. As the field of FASD moves forward, it will be
      important to adopt a single set of diagnostic guidelines worldwide. To achieve
      this, the performance (validity) of current diagnostic guidelines must be
      rigorously assessed and reported. OBJECTIVE: To summarize the body of evidence
      that has amassed over 20 years that validates the performance of the FASD 4-Digit
      Diagnostic Code. METHODS: The evidence validating the 4-Digit Code is documented
      across 35 studies published between 1992 and 2012, including new information
      presented in this report. These studies and data sources include the delineation
      of the FAS facial phenotype; creation of the 4-Digit Code (1997-2004); our 10
      year, foster-care FAS screening program; our MRI/fMRI/MRS studies; analysis of
      2,550 individuals evaluated for FASD over 20 years in the WA State FASDPN
      clinics, and analysis of 622 patient satisfaction/follow-up surveys; surveys of
      10,000 professionals attending the University of Washington FASD diagnostic
      clinic trainings; and surveys of over 700 professionals worldwide who completed
      the 4-Digit Code Online Course. CONCLUSION: The 4-Digit Code is a simple,
      comprehensive, evidence-based, validated diagnostic system. It has served as the
      cornerstone of a fully integrated FASD screening, diagnostic, intervention,
      prevention, and surveillance program in Washington State for the past 20 years.

PMID- 24323702
TI  - Comparison of three summary statistics for ranking genes in genome-wide
      association studies.
AB  - Problems associated with insufficient power have haunted the analysis of genome
      wide association studies and are likely to be the main challenge for the analysis
      of next-generation sequencing data. Ranking genes according to their strength of
      association with the investigated phenotype is one solution. To obtain rankings
      for genes, researchers can draw from a wide range of statistics summarizing the
      relationships between variants mapped to a gene and the phenotype. Hence, it is
      of interest to explore the performance of these statistics in the context of
      rankings. To this end, we conducted a simulation study (limited to genes of equal
      sizes) of three different summary statistics examining the ability to rank genes
      in a meaningful order. The weighted sum of squared marginal score test (Pan,
      2009), RareCover algorithm (Bahtia et al., 2010) and the elastic net
      regularization (Zou and Hastie, 2005) were chosen, because they can handle common
      as well as rare variants. The test based on the score statistic outperformed both
      other methods in almost all investigated scenarios. It was the only measure to
      consistently detect genes with interacting causal variants. However, the
      RareCover algorithm proved better at identifying genes including causal variants
      with small effect sizes and low minor allele frequency than the weighted sum of
      squared marginal score test. The performance of the elastic net regularization
      was unimpressive for all but the simplest scenarios.

PMID- 24323703
TI  - Evaluation of biocompatibility and degradation of chitosan nanofiber membrane
      crosslinked with genipin.
AB  - Chitosan, a natural polysaccharide, has demonstrated potential as a degradable
      biocompatible guided bone regeneration membrane. This study aimed to evaluate the
      in vivo biocompatibility and degradation of chitosan nanofiber membranes, with
      and without genipin crosslinking as compared with a commercial collagen membrane
      in rat model. Chitosan nanofiber membranes, with and without genipin
      crosslinking, and collagen membrane (control) were implanted subcutaneously in
      the backs of 30 rats. The membranes were analyzed histologically at 2, 4, 8, 12,
      16, and 20 weeks. Sections were viewed and graded by a blinded pathologist using
      a 4-point scoring system (0 = absent, 1 = mild, 2 = moderate, and 3 = severe) to
      determine the tissue reaction to the membranes and to observe membrane
      degradation. There was no statistically significant difference in histological
      scores among chitosan and collagen membranes at different time points. Absence or
      minimal inflammation was observed in 57-74% of the membranes across all groups.
      Most chitosan membranes persisted for 16-20 weeks, whereas most collagen
      membranes disappeared by resorption at 12-16 weeks. The general tissue response
      to chitosan nanofiber membranes with and without genipin crosslinking, was
      similar to that of control commercial collagen membrane. However, the chitosan
      membranes exhibited slower degradation rates than collagen membranes.

PMID- 24323704
TI  - Dopamine modulates frontomedial failure processing of agentic introverts versus
      extraverts in incentive contexts.
AB  - The agency facet of extraversion (aE) describes individual differences in goal
      directed behavior and has been linked to dopamine function in incentive contexts.
      Because dopamine presumably modulates the processing of negative
      feedback/failure, aE may relate to failure processing in incentive contexts. To
      test this hypothesis, N = 86 participants performed a virtual ball-catching task.
      An incentive context was created by displaying potential rewards and subtle
      manipulations of task performance, which either was (control group) or was not
      (incentive context group) made explicit. To probe the involvement of dopamine,
      participants received either placebo or the selective dopamine D2 receptor
      antagonist sulpiride (200 mg). Failure processing was assessed through negative
      feedback-evoked differences in the frontal midline theta electroencephalogram
      power (DFMT) and in the feedback-related negativity event-related potential
      component (FRN). Before incentives were introduced, DFMT (but not the FRN) was
      related to neuroticism/anxiety. Importantly, once incentives were displayed, aE
      was associated with DFMT, FRN, task performance, and changes in self-reported
      positive affect, which further depended on incentive context group and/or
      substance group: In the incentive context group but not in the control group,
      agentic extraverts showed relatively blunted DFMT after placebo. Sulpiride
      significantly enhanced DFMT, whereas it reduced FRN amplitudes and performance in
      agentic extra- versus introverts. These findings provide strong support for
      current dopamine models of aE and failure processing, and also highlight the
      importance of task context. Moreover, the dissociations of FRN and DFMT suggest
      the existence of two nonredundant electrophysiological indices of feedback
      processing, both relating to dopamine and aE. 

PMID- 24323705
TI  - Cognitive control of familiarity: directed forgetting reduces proactive
      interference in working memory.
AB  - Proactive interference (PI) occurs when previously learned information interferes
      with new learning. In a working memory task, PI induces longer response times and
      more errors to recent negative probes than to new probes, presumably because the
      recent probe's familiarity invites a "yes" response. Warnings, longer intertrial
      intervals, and the increased contextual salience of the probes can reduce but not
      eliminate PI, suggesting that cognitive control over PI is limited. Here we
      tested whether control exerted in the form of intentional forgetting performed
      during working memory can reduce the magnitude of PI. In two experiments,
      participants performed a working memory task with directed-forgetting
      instructions and the occasional presentation of recent probes. Surprise long-term
      memory testing indicated better memory for to-be-remembered than for to-be
      forgotten items, documenting the classic directed-forgetting effect. Critically,
      in working memory, PI was virtually eliminated for recent probes from prior to-be
      forgotten lists, as compared to recent probes from prior to-be-remembered lists.
      Thus cognitive control, when executed via directed forgetting, can reduce the
      adverse and otherwise persistent interference from familiarity, an effect that we
      attribute to attenuated memory representations of the to-be-forgotten items. 

PMID- 24323706
TI  - Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and
      global cerebral ischemia.
AB  - We previously showed that palmitic acid methyl ester (PAME) and stearic acid
      methyl ester (SAME) are simultaneously released from the sympathetic ganglion and
      PAME possesses potent vasodilatory properties which may be important in cerebral
      ischemia. Since PAME is a potent vasodilator simultaneously released with SAME,
      our hypothesis was that PAME/SAME confers neuroprotection in rat models of
      focal/global cerebral ischemia. We also examined the neuroprotective properties
      of Solutol HS15, a clinically approved excipient because it possesses similar
      fatty acid compositions as PAME/SAME. Asphyxial cardiac arrest (ACA, 6 min) was
      performed 30 min after PAME/SAME treatment (0.02 mg/kg, IV). Solutol HS15 (2
      ml/kg, IP) was injected chronically for 14 days (once daily). Histopathology of
      hippocampal CA1 neurons was assessed 7 days after ACA. For focal ischemia
      experiments, PAME, SAME, or Solutol HS15 was administered following reperfusion
      after 2 h of middle cerebral artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium
      staining of the brain was performed 24 h after MCAO and the infarct volume was
      quantified. Following ACA, the number of surviving hippocampal neurons was
      enhanced by PAME-treated (68%), SAME-treated (69%), and Solutol-treated HS15
      (68%) rats as compared to ACA only-treated groups. Infarct volume was decreased
      by PAME (83%), SAME (68%), and Solutol HS15 (78%) as compared to saline (vehicle)
      in MCAO-treated animals. PAME, SAME, and Solutol HS15 provide robust
      neuroprotection in both paradigms of ischemia. This may prove therapeutically
      beneficial since Solutol HS15 is already administered as a solublizing agent to
      patients. With proper timing and dosage, administration of Solutol HS15 and
      PAME/SAME can be an effective therapy against cerebral ischemia.

PMID- 24323708
TI  - Early MoCA-assessed cognitive impairment after aneurysmal subarachnoid hemorrhage
      and relationship to 1-year functional outcome.
AB  - Recent clinical research into aneurysmal subarachnoid hemorrhage (aSAH) has
      confirmed the long-term effect of cognitive dysfunction on functional outcomes.
      We hypothesized that early cognitive impairment was a marker of permanent brain
      injury and hence predicted long-term functional outcome. Hong Kong Chinese
      patients with aneurysmal subarachnoid hemorrhage were evaluated prospectively by
      means of the Montreal Cognitive Assessment (MoCA) in the subacute phase (2-4
      weeks after aSAH) and by neuropsychological evaluation of functional outcomes in
      the chronic phase (1 year after aSAH). This multi-center prospective
      observational study is registered at ClinicalTrials.gov of the US National
      Institutes of Health (NCT01038193). One hundred and eight patients completed both
      the subacute and chronic phase assessments. Cognitive dysfunction in the subacute
      phase independently correlated with functional outcomes at 1 year, after
      adjusting for age, admission clinical condition, treatment modality, motor score,
      and mobility in the subacute phase, but the positive predictive values remained
      low. MoCA-assessed cognitive impairment in the subacute phase cannot accurately
      predict functional outcomes at 1 year. Future study should focus on understanding
      the relative importance of different components of early cognitive impairment.

PMID- 24323707
TI  - Mitochondrial dysfunction induced by nuclear poly(ADP-ribose) polymerase-1: a
      treatable cause of cell death in stroke.
AB  - Many drugs targeting excitotoxic cell death have demonstrated robust
      neuroprotective effects in animal models of cerebral ischemia. However, these
      neuroprotective effects have almost universally required drug administration at
      relatively short time intervals after ischemia onset. This finding has translated
      to clinical trial results; interventions targeting excitotoxicity have had no
      demonstrable efficacy when initiated hours after ischemia onset, but beneficial
      effects have been reported with more rapid initiation. Consequently, there
      continues to be a need for interventions with efficacy at later time points after
      ischemia. Here, we focus on mitochondrial dysfunction as both a relatively late
      event in ischemic neuronal death and a recognized cause of delayed neuronal
      death. Activation of poly(ADP-ribose) polymerase-1 (PARP-1) is a primary cause of
      mitochondrial depolarization and subsequent mitochondria-triggered cell death in
      ischemia reperfusion. PARP-1 consumes cytosolic NAD(+), thereby blocking both
      glycolytic ATP production and delivery of glucose carbon to mitochondria for
      oxidative metabolism. However, ketone bodies such as pyruvate, beta- and gamma
      hydroxybutyrate, and 1,4-butanediol can fuel mitochondrial metabolism in cells
      with depleted cytosolic NAD(+) as long as the mitochondria remain functional.
      Ketone bodies have repeatedly been shown to be highly effective in preventing
      cell death in animal models of ischemia, but a rigorous study of the time window
      of opportunity for this approach remains to be performed. 

PMID- 24323709
TI  - ABCD2 score may discriminate minor stroke from TIA on patient admission.
AB  - With the advent of time-dependent thrombolytic therapy for ischemic stroke, it
      has become increasingly important to differentiate transient ischemic attack
      (TIA) from minor stroke patients after symptom onset quickly. This study
      investigated the difference between TIA and minor stroke based on age, blood
      pressure, clinical features, duration of TIA, presence of diabetes, ABCD2 score,
      digital subtraction angiography (DSA) and blood lipids. One hundred seventy-one
      patients with clinical manifestations as transient neurological deficits in
      Nanjing Drum Tower Hospital were studied retrospectively. All patients were
      evaluated by ABCD2 score, blood lipid test, fibrinogen, and Holter
      electrocardiograph and DSA on admission. Patients were categorized into TIA group
      or minor stroke group according to CT and MRI scan 24 h within symptom onset. The
      study suggested that minor stroke patients were more likely to have a higher
      ABCD2 score (odds ratio (OR) 2.060; 95% confidence interval (CI) 1.293-3.264).
      Receiver-operating characteristic curves identified ABCD2 score >4 as the optimal
      cut-off for minor stroke diagnosis. Total serum cholesterol seemed a better
      diagnostic indicator to discriminate minor stroke from TIA (OR 4.815; 95% CI
      0.946-1.654) than other blood lipids in simple logistic regression, but not
      valuable for the differentiation between TIA and minor stroke in multivariate
      logistic regression. Higher severity of intracranial internal carotid stenosis,
      especially >90%, were more likely to have minor stroke, but was not a reliable
      diagnostic indicator (P > 0.05). ABCD2 could help clinicians to differentiate
      possible TIA from minor stroke at hospital admission while blood lipid parameters
      and artery stenosis location offer limited help.

PMID- 24323710
TI  - Tumor necrosis factor-alpha modulates cerebral aneurysm formation and rupture.
AB  - Inflammation is a critical process behind cerebral aneurysm formation and
      rupture. Tumor necrosis factor alpha (TNF-alpha) is a key immune modulator that
      has been implicated in cerebral aneurysm pathophysiology. This may occur through
      TNF-alpha-mediated endothelial injury, smooth muscle cell phenotypic modulation,
      recruitment of macrophages, activation of chemotactic cytokines, upregulation of
      matrix remodeling genes, production of free radicals leading to oxidative stress,
      and ultimately cellular apoptosis. Recent studies have indicated that TNF-alpha
      may be a potential target for the development of novel medical therapies, but
      additional experimental data is needed to clarify the intricacies of TNF-alpha
      activation and its critical downstream targets in cerebral aneurysms. This review
      provides an update on the mechanisms underlying TNF-alpha-induced molecular
      modulation in cerebral aneurysms. 

PMID- 24323711
TI  - Thrombin-induced cerebral hemorrhage: role of protease-activated receptor-1.
AB  - Thrombin causes blood-brain barrier disruption, and this study examined whether
      thrombin can cause brain hemorrhage through protease-activated receptor-1 (PAR
      1). Male wild type and PAR-1 knockout mice had an intracerebral injection of
      thrombin or saline. Mice then underwent serial T2 magnetic resonance imaging and
      were euthanized for brain hemoglobin, iron, and interleukin-1beta measurements.
      Thrombin caused massive T2 lesions and brain hemorrhage in wild type mice. These
      effects were markedly reduced in PAR-1 knockout mice. Thrombin also increased
      brain interleukin-1beta, and this was absent in PAR-1 knockout mice. In
      conclusion, thrombin increases interleukin-1beta levels and induces intracerebral
      hemorrhage through PAR-1 activation. 

PMID- 24323712
TI  - Microglial voltage-gated proton channel Hv1 in ischemic stroke.
AB  - Microglia, resident immune cells in the brain, contribute both to the damage and
      resolution of ischemic stroke. However, the mechanisms of microglia's detrimental
      or beneficial role in the disease are poorly understood. The voltage-gated proton
      channel, Hv1, rapidly removes protons from depolarized cytoplasm, and is highly
      expressed in the immune system. In the brain, Hv1 is selectively and functionally
      expressed in microglia but not neurons. Although the physiological function of
      microglial Hv1 is still not clear, Hv1 is one of major ion channels expressed in
      resting microglia. Under pathological conditions, microglial Hv1 is required for
      NADPH oxidase (NOX)-dependent generation of reactive oxygen species (ROS) by
      providing charge compensation for exported electrons and relieving intracellular
      acidosis. In a mouse model of cerebral middle artery occlusion, Hv1 knockout mice
      are protected from ischemic damage, showing reduced NOX-dependent ROS production,
      microglial activation and neuronal cell death. Therefore, microglial Hv1 aids in
      NOX-dependent ROS generation, which subsequently induces neuronal cell death and
      a significant fraction of brain damage after ischemic stroke. These studies
      illuminate a critical role of microglial Hv1 in ischemic brain injury, providing
      a rationale for Hv1 as a potential therapeutic target for the treatment of
      ischemic stroke. The current understanding of Hv1 in ischemic injury through NOX
      dependent ROS production may serve as a common model to reveal the deleterious
      role of microglia in neurological diseases other than ischemic stroke, such as
      multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, and
      neuropathic pain. 

PMID- 24323713
TI  - Vascular smooth muscle cells in cerebral aneurysm pathogenesis.
AB  - Vascular smooth muscle cells (SMC) maintain significant plasticity. Following
      environmental stimulation, SMC can alter their phenotype from one primarily
      concerned with contraction to a pro-inflammatory and matrix remodeling phenotype.
      This is a critical process behind peripheral vascular disease and
      atherosclerosis, a key element of cerebral aneurysm pathology. Evolving evidence
      demonstrates that SMCs and phenotypic modulation play a significant role in
      cerebral aneurysm formation and rupture. Pharmacological alteration of smooth
      muscle cell function and phenotypic modulation could provide a promising medical
      therapy to inhibit cerebral aneurysm progression. This study reviews vascular SMC
      function and its contribution to cerebral aneurysm pathophysiology. 

PMID- 24323714
TI  - Molecular imaging of cerebrovascular lesions.
AB  - Inflammation is a key component in the pathogenesis of cerebrovascular lesions.
      Two agents have emerged as promising possibilities for imaging cerebrovascular
      lesions. These agents are ferumoxytol and myeloperoxidase (MPO)-specific
      paramagnetic magnetic resonance (MR) contrast agent. Ferumoxytol is an iron oxide
      nanoparticle coated by a carbohydrate shell that is used in MRI studies as an
      inflammatory marker as it is cleared by macrophages. Ferumoxytol-enhanced MRI
      allows noninvasive assessment of the inflammatory status of cerebral aneurysms
      and arteriovenous malformations and, possibly, may differentiate "unstable"
      lesions that require early intervention from "stable" lesions that can be safely
      observed. Several pilot studies have also suggested that MPO-specific
      paramagnetic MR contrast agent, di-5-hydroxytryptamide of gadopentetate
      dimeglumine, may allow imaging of inflammation in the wall of saccular aneurysms
      in animal models. However, studies in human subjects have yet to be performed. In
      this paper, we review current data regarding ferumoxytol-enhanced MRI and MPO
      specific paramagnetic MR contrast agent and discuss current and future
      applications. 

PMID- 24323715
TI  - Cerebral lactate correlates with early onset pneumonia after aneurysmal SAH.
AB  - Pneumonia is a significant medical complication following aneurysmal subarachnoid
      hemorrhage (aSAH). The aSAH may initiate immune interactions leading to depressed
      immunofunction, followed by an increased risk of infection. It remains unclear as
      to whether there is a possible association between cerebral metabolism and
      infections. Clinical and microdialysis data from aSAH patients prospectively
      included in the CoOperative Study on Brain Injury Depolarisations protocol Berlin
      were analyzed. Levels of glucose, lactate, pyruvate, and glutamate were measured
      hourly using microdialysis in the cerebral extracellular fluid. The occurrence of
      pneumonia (defined by positive microbiological cultures) and delayed ischemic
      neurological deficits (DIND) was documented prospectively. Eighteen aSAH patients
      (52.7 +/- 10.7 years), classified according to the World Federation of
      Neurological Surgeons in low (I-III, n = 9) and high (IV-V, n = 9) grades, were
      studied. Eight patients (45%) experienced DIND, 10 patients (56%) pneumonia (mean
      onset day 2.6). Lactate was elevated at day 3 in infected patients (n = 9, median
      = 6.82 mmol/L) vs. patient without infections (n = 6, median = 2.90 mmol/L, p =
      0.036). The optimum cut-off point to predict pneumonia at day 3 was 3.57 mmol/L
      with a sensitivity of 0.77, and a specificity of 0.66 (area under curve was 0.833
      with p = 0.034). Lactate at day 7 was higher in DIND patients compared to no-DIND
      patients (p = 0.016). Early elevated lactate correlated with occurrence of
      bacterial pneumonia, while late elevations with DIND after aSAH. Future
      investigations may elucidate the relationship between cerebral lactate and
      markers of immunocompetence and more detailed to identify patients with higher
      susceptibility for infections.

PMID- 24323716
TI  - Post-stroke apathy and hypersomnia lead to worse outcomes from acute
      rehabilitation.
AB  - Apathy and hypersomnia occur after stroke and, by definition, reduce
      participation in rehabilitation, but their effect on outcome from acute
      rehabilitation is not known. We performed a retrospective review of 213 patients
      admitted to a stroke-specialized acute rehabilitation unit in the United States.
      All patients had ischemic or hemorrhagic stroke, and no dementia or dependence on
      others pre-stroke. We diagnosed apathy and hypersomnia using standardized
      documentation by treating therapists. We used multiple regression analysis to
      control for overall impairment (combination of strength, cognitive and sensory
      measures), age, time since stroke, and stroke type (ischemic or hemorrhagic).
      Forty-four (21%) of the patients had persistent apathy, and 12 (5.6%) had
      persistent hypersomnia. Both groups were more impaired in cognition, sustained
      attention, and more likely to be treated for depression. Patients with apathy
      were 2.4 times more likely to go to a nursing home, and had discharge FIM scores
      12 points below the mean. Patients with hypersomnia were ten times more likely to
      go to a nursing home, and had discharge FIM scores 16 points below the mean.
      These findings indicate that studies to prospectively define these clinical
      factors and potential confounds using standardized tools are indicated, and if
      confirmed, justify studies to identify these patients early and develop targeted
      interventions.

PMID- 24323717
TI  - Cerebral aneurysms: formation, progression, and developmental chronology.
AB  - The prevalence of unruptured intracranial aneurysms (UIAs) in the general
      population is up to 3%. Existing epidemiological data suggests that only a small
      fraction of UIAs progress towards rupture over the lifetime of an individual, but
      the surrogates for subsequent rupture and the natural history of UIAs are
      discussed very controversially at present. In case of rupture of an UIA, the case
      fatality is up to 50%, which therefore continues to stimulate interest in the
      pathogenesis of cerebral aneurysm formation and progression. Actual data on the
      chronological development of cerebral aneurysm has been especially difficult to
      obtain and, until recently, the existing knowledge in this respect is mainly
      derived from animal or mathematical models or short-term observational studies.
      Here, we review the current data on cerebral aneurysm formation and progression
      as well as a novel approach to investigate the developmental chronology of
      cerebral aneurysms.

PMID- 24323718
TI  - Relation of platelet C4d with all-cause mortality and ischemic stroke in patients
      with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease associated with
      significant morbidity, including premature cardiovascular disease, and mortality.
      Platelets bearing complement protein C4d (P-C4d) were initially determined to be
      specific for diagnosis of SLE and were later found to be associated with acute
      ischemic stroke in non-SLE patients. P-C4d may identify a subset of SLE patients
      with a worse clinical prognosis. This study investigated the associations of P
      C4d with all-cause mortality and vascular events in a lupus cohort. A cohort of
      356 consecutive patients with SLE was followed from 2001 to 2009. Primary outcome
      was all-cause mortality. Secondary outcomes were vascular events (myocardial
      infarction, coronary artery bypass graft, percutaneous coronary transluminal
      angioplasty, ischemic stroke, venous thromboembolism, pulmonary embolism, or
      other thrombosis). P-C4d was measured at study baseline. Seventy SLE patients
      (19.7%) had P-C4d. Mean follow-up was 4.7 years. All-cause mortality was 4%. P
      C4d was associated with all-cause mortality (hazard ratio 7.52, 95% confidence
      interval (CI) 2.14-26.45, p = 0.002) after adjusting for age, ethnicity, sex,
      cancer, and anticoagulant use. Vascular event rate was 21.6%. Patients with
      positive P-C4d were more likely to have had vascular events compared to those
      with negative P-C4d (35.7 vs. 18.2%, p = 0.001). Specifically, P-C4d was
      associated with ischemic stroke (odds ratio 4.54, 95% CI 1.63-12.69, p = 0.004)
      after adjusting for age, ethnicity, and antiphospholipid antibodies. Platelet-C4d
      is associated with all-cause mortality and stroke in SLE patients. P-C4d may be a
      prognostic biomarker as well as a pathogenic clue that links platelets,
      complement activation, and thrombosis.

PMID- 24323719
TI  - Translational research using a mouse model of intracranial aneurysm.
AB  - We have developed a mouse model of intracranial aneurysm that recapitulates key
      features of human intracranial aneurysms. In this model, spontaneous aneurysmal
      rupture occurs with a predictable time course. Aneurysmal rupture in this model
      can be easily detected by assessing neurological symptoms. Similar to human
      intracranial aneurysms, intracranial aneurysms in this model show an infiltration
      with inflammatory cells. This mouse model can be used to study the mechanisms and
      the potential preventive treatments for aneurysmal rupture. 

PMID- 24323721
TI  - Effects of androgens on early post-ischemic neurogenesis in mice.
AB  - Although androgens are reported to affect stroke outcomes by altering ischemic
      tissue damage, their effect on post-injury repair is unknown. Since neurogenesis
      has recently been recognized as contributing to stroke outcomes, we investigated
      the role of androgens on stroke-induced neurogenesis. Adult male mice were
      subjected to transient middle cerebral artery occlusion (MCAO) and neurogenesis
      was examined 1 week later by quantifying BrdU/doublecortin-positive and BrdU/NeuN
      positive neurons in brain germinal regions as well as the injured striatum. To
      elucidate the role of endogenous androgens, post-MCAO neurogenesis was examined
      in gonadally intact males, intact males implanted with the androgen receptor
      antagonist flutamide, and surgically castrated males. Surgical castration or
      pharmacologic androgen receptor blockade had no effects on post-ischemic
      neurogenesis, except that continuous androgen receptor blockade unexpectedly
      suppressed maturation of newborn neurons (BrdU/NeuN-positive cells) in the
      dentate gyrus. Post-MCAO neurogenesis was also examined in surgically castrated
      mice treated with continuous release implants containing testosterone or
      dihydrotestosterone (DHT). Testosterone and DHT robustly inhibited post-ischemic
      neurogenesis in the dentate gyrus, and the more potent androgen DHT virtually
      abolished the presence of immature newborn neurons (BrdU/doublecortin-positive
      cells) in the injured striatum. Our data suggest that endogenous androgens do not
      alter post-stroke neurogenesis quantitatively, but the presence of supra
      physiological androgen stimulation profoundly suppresses early neurogenesis in
      germinal brain areas and reduces cellular repair in injured tissue after cerebral
      ischemia. These results advance the understanding of the role that androgens play
      in stroke outcomes.

PMID- 24323722
TI  - Smooth muscle phenotype switching in blast traumatic brain injury-induced
      cerebral vasospasm.
AB  - Due to increased survival rates among soldiers exposed to explosive blasts, blast
      induced traumatic brain injury (bTBI) has become much more prevalent in recent
      years. Cerebral vasospasm (CVS) is a common manifestation of brain injury whose
      incidence is significantly increased in bTBI. CVS is characterized by initial
      vascular smooth muscle cell (VSMC) hypercontractility, followed by prolonged
      vessel remodeling and lumen occlusion, and is traditionally associated with
      subarachnoid hemorrhage (SAH), but recent results suggest that mechanical injury
      during bTBI can cause mechanotransduced VSMC hypercontractility and phenotype
      switching necessary for CVS development, even in the absence of SAH. Here, we
      review the mechanisms by which mechanical stimulation and SAH can synergistically
      drive CVS progression, complicating treatment options in bTBI patients. 

PMID- 24323720
TI  - Voltage-gated potassium channels at the crossroads of neuronal function, ischemic
      tolerance, and neurodegeneration.
AB  - Voltage-gated potassium (Kv) channels are widely expressed in the central and
      peripheral nervous system and are crucial mediators of neuronal excitability.
      Importantly, these channels also actively participate in cellular and molecular
      signaling pathways that regulate the life and death of neurons. Injury-mediated
      increased K(+) efflux through Kv2.1 channels promotes neuronal apoptosis,
      contributing to widespread neuronal loss in neurodegenerative disorders such as
      Alzheimer's disease and stroke. In contrast, some forms of neuronal activity can
      dramatically alter Kv2.1 channel phosphorylation levels and influence their
      localization. These changes are normally accompanied by modifications in channel
      voltage dependence, which may be neuroprotective within the context of ischemic
      injury. Kv1 and Kv7 channel dysfunction leads to neuronal hyperexcitability that
      critically contributes to the pathophysiology of human clinical disorders such as
      episodic ataxia and epilepsy. This review summarizes the neurotoxic,
      neuroprotective, and neuroregulatory roles of Kv channels and highlights the
      consequences of Kv channel dysfunction on neuronal physiology. The studies
      described in this review thus underscore the importance of normal Kv channel
      function in neurons and emphasize the therapeutic potential of targeting Kv
      channels in the treatment of a wide range of neurological diseases. 

PMID- 24323723
TI  - Vascular neural network phenotypic transformation after traumatic injury:
      potential role in long-term sequelae.
AB  - The classical neurovascular unit (NVU), composed primarily of endothelium,
      astrocytes, and neurons, could be expanded to include smooth muscle and
      perivascular nerves present in both the up- and downstream feeding blood vessels
      (arteries and veins). The extended NVU, which can be defined as the vascular
      neural network (VNN), may represent a new physiological unit to consider for
      therapeutic development in stroke, traumatic brain injury, and other brain
      disorders (Zhang et al., Nat Rev Neurol 8(12):711-716, 2012). This review is
      focused on traumatic brain injury and resultant post-traumatic changes in
      cerebral blood flow, smooth muscle cells, matrix, blood-brain barrier structures
      and function, and the association of these changes with cognitive outcomes as
      described in clinical and experimental reports. We suggest that studies
      characterizing TBI outcomes should increase their focus on changes to the VNN, as
      this may yield meaningful therapeutic targets to resolve posttraumatic
      dysfunction. 

PMID- 24323724
TI  - Acid-sensing ion channels contribute to neurotoxicity.
AB  - Acidosis that occurs under pathological conditions not only affects intracellular
      signaling molecules, but also directly activates a unique family of ligand-gated
      ion channels: acid-sensing ion channels (ASICs). ASICs are widely expressed
      throughout the central and peripheral nervous systems and play roles in pain
      sensation, learning and memory, and fear conditioning. Overactivation of ASICs
      contributes to neurodegenerative diseases such as ischemic brain/spinal cord
      injury, multiple sclerosis, Parkinson's disease, and Huntington's disease. Thus,
      targeting ASICs might be a potential therapeutic strategy for these conditions.
      This mini-review focuses on the electrophysiology and pharmacology of ASICs and
      roles of ASICs in neuronal toxicity. 

PMID- 24323725
TI  - Smooth muscle cell phenotypic switching in stroke.
AB  - Disruption of cerebral blood flow after stroke induces cerebral tissue injury
      through multiple mechanisms that are not yet fully understood. Smooth muscle
      cells (SMCs) in blood vessel walls play a key role in cerebral blood flow
      control. Cerebral ischemia triggers these cells to switch to a phenotype that
      will be either detrimental or beneficial to brain repair. Moreover, SMC can be
      primarily affected genetically or by toxic metabolic molecules. After stroke,
      this pathological phenotype has an impact on the incidence, pattern, severity,
      and outcome of the cerebral ischemic disease. Although little research has been
      conducted on the pathological role and molecular mechanisms of SMC in
      cerebrovascular ischemic diseases, some therapeutic targets have already been
      identified and could be considered for further pharmacological development. We
      examine these different aspects in this review. 

PMID- 24323726
TI  - Disruption of ion homeostasis in the neurogliovascular unit underlies the
      pathogenesis of ischemic cerebral edema.
AB  - Cerebral edema is a major cause of morbidity and mortality following ischemic
      stroke, but its underlying molecular pathophysiology is incompletely understood.
      Recent data have revealed the importance of ion flux via channels and
      transporters expressed in the neurogliovascular unit in the development of
      ischemia-triggered cytotoxic edema, vasogenic edema, and hemorrhagic conversion.
      Disruption of homeostatic mechanisms governing cell volume regulation and
      epithelial/endothelial ion transport due to ischemia-associated energy failure
      results in the thermodynamically driven re-equilibration of solutes and water
      across the CSF-blood and blood-brain barriers that ultimately increases the
      brain's extravascular volume. Additionally, hypoxia, inflammation, and other
      stress-triggered increases in the functional expression of ion channels and
      transporters normally expressed at low levels in the neurogliovascular unit cause
      disruptions in ion homeostasis that contribute to ischemic cerebral edema. Here,
      we review the pathophysiological significance of several molecular mediators of
      ion transport expressed in the neurogliovascular unit, including targets of
      existing FDA-approved drugs, which might be potential nodes for therapeutic
      intervention. 

PMID- 24323727
TI  - Does Na+/Ca2+ exchanger, NCX, represent a new druggable target in stroke
      intervention?
AB  - Stroke causes a rapid cell death in the core of the injured region and triggers
      mechanisms in surrounding penumbra area that leads to changes in concentrations
      of several ions like intracellular Ca2+, Na+, H+, K+, and radicals such as
      reactive oxygen species and reactive nitrogen species. When a dysregulation of
      homeostasis of these messengers occurs, it can trigger cell death. In particular,
      it is widely accepted that a critical factor in determining neuronal death during
      cerebral ischemia is progressive dysregulation of Ca2+, Na+, K+, and H+
      homeostasis that activate several death pathways, including oxidative and
      nitrosative stress, mitochondrial dysfunction, protease activation, and
      apoptosis. In the last decade, several seminal experimental works are markedly
      changing the scenario of research of principal players of an ischemic event.
      Indeed, some plasma membrane channels and transporters, involved in the control
      of Ca2+, Na+, K+, and H+ ion influx or efflux and, therefore, responsible for
      maintaining the homeostasis of these four cations, might function as crucial
      players in initiation of brain ischemic process. Indeed, these proteins, by
      regulating ionic homeostasis, may provide the molecular basis underlying
      glutamate-independent Ca2+ and Na+ overload mechanisms in neuronal ischemic cell
      death and, most importantly, may represent more suitable molecular targets for
      therapeutic intervention. Recently, a great deal of interest has been devoted to
      clarify the role of the plasma membrane protein known as Na+/Ca2+ exchanger, a
      transporter able to control Na+ and Ca2+ homeostasis. In this review, the
      pathophysiological role of NCX and its implication as a potential target in
      stroke intervention will be examined.

PMID- 24323728
TI  - Alzheimer's silent partner: cerebral amyloid angiopathy.
AB  - Alzheimer's disease (AD) is the most common form of dementia, which completely
      lacks a viable, long-term therapeutic intervention. This is partly due to an
      incomplete understanding of AD etiology and the possible confounding factors
      associated with its genotypic and phenotypic heterogeneity. Cerebral amyloid
      angiopathy (CAA) is a common, yet frequently overlooked, pathology associated
      with AD. CAA manifests with deposition amyloid-beta (Abeta) within the smooth
      muscle layer of cerebral arteries and arterioles. The role of Abeta in AD and CAA
      pathophysiology has long been controversial. Although it has demonstrated
      toxicity at super-physiological levels in vitro, Abeta load does not necessarily
      correlate with cognitive demise in humans. In this review, we describe the
      contributions of CAA to AD pathophysiology and important pathomechanisms that may
      lead to vascular fragility and hemorrhages. Additionally, we discuss the effect
      of Abeta on smooth muscle cell phenotype and viability, especially in terms of
      the complement cascade. 

PMID- 24323729
TI  - Phenotypic transformation of smooth muscle in vasospasm after aneurysmal
      subarachnoid hemorrhage.
AB  - Differentiated smooth muscle cells (SMC) control vasoconstriction and
      vasodilation, but they can undergo transformation, proliferate, secret cytokines,
      and migrate into the subendotherial layer with adverse consequences. In this
      review, we discuss the phenotypic transformation of SMC in cerebral vasospasm
      after subarachnoid hemorrhage. Phenotypic transformation starts with an insult as
      caused by aneurysm rupture: Elevation of intracranial and blood pressure,
      secretion of norepinephrine, and mechanical force on an artery are factors that
      can cause aneurysm. The phenotypic transformation of SMC is accelerated by
      inflammation, thrombin, and growth factors. A wide variety of cytokines (e.g.,
      interleukin (IL)-1beta, IL-33, matrix metalloproteinases, nitric oxidase
      synthases, endothelins, thromboxane A2, mitogen-activated protein kinase,
      platelet-derived vascular growth factors, and vascular endothelial factor) all
      play roles in cerebral vasospasm (CVS). We summarize the correlations between
      various factors and the phenotypic transformation of SMC. A new target of this
      study is the transient receptor potential channel in CVS. Statin together with
      fasdil prevents phenotypic transformation of SMC in an animal model. Clazosentan
      prevents CVS and improves outcome in aneurysmal subarachnoid hemorrhage in a dose
      dependent manner. Clinical trials of cilostazol for the prevention of phenotypic
      transformation of SMC have been reported, along with requisite experimental
      evidence. To conquer CVS in its complexity, we will ultimately need to elucidate
      its general, underlying mechanism. 

PMID- 24323730
TI  - Endovascular management of cerebral aneurysm : review of the literature.
AB  - Management of intracranial aneurysms remains controversial. For unruptured
      aneurysms, many factors should be taken into account before deciding the type of
      treatment and whether to treat or not. Ruptured aneurysms on the other hand are
      almost always treated. Still, the question remains what are the indicators that
      one must rely on to decide what treatment suits the patient best. We present a
      review on the management of intracranial aneurysm while focusing on endovascular
      aspects. 

PMID- 24323731
TI  - Erythropoietin inhibits HIF-1alpha expression via upregulation of PHD-2
      transcription and translation in an in vitro model of hypoxia-ischemia.
AB  - Hypoxia inducible factor (HIF)-1alpha is the central transcriptional factor for
      the regulation of oxygen-associated genes in response to hypoxia. Erythropoietin
      (EPO), a hematopoietic growth factor, increases oxygen availability during
      hypoxia/ischemia and is associated with neuroprotection following hypoxia
      ischemia in laboratory models of stroke. However, EPO has failed to translate in
      a clinical setting. Thus, it is critical to elucidate the key players in EPO
      induced neuroprotection. Our preliminary studies have shown that EPO, as a
      downstream gene of HIF, inhibits HIF-1alpha in a dose-dependent manner in an in
      vitro model of hypoxia-ischemia. This study is designed to elucidate the primary
      mediator of EPO-induced HIF-1alpha inhibition and subsequent cell
      survival/neuroprotection. Oxygen and glucose deprivation (OGD) of nerve growth
      factor-differentiated rat pheochromocytoma (PC-12) cells were used to model
      hypoxia-ischemia in an in vitro environment. The profile of HIF-1alpha, HIF
      2alpha and prolyl hydroxylase domain 2 (PHD-2) expression; HIF-1alpha and prolyl
      hydroxylase (PHD-2) mRNA levels; matrix metalloproteinase (MMP)-9; and cell death
      was evaluated in the presence and absence of either EPO or PHD-2 inhibitor during
      OGD. Our findings showed that EPO treatment resulted in an increase in PHD-2
      transcription and translation, inhibition of HIF-1alpha expression, reactive
      oxygen species formation, and MMP-9 activity, resulting in increased cell
      survival after OGD. We also observed that EPO-induced cell
      survival/neuroprotection was reversed by siRNA silencing of PHD-2. This led to
      the conclusion that PHD-2 is a key mediator of EPO-induced HIF-1alpha inhibition
      and subsequent neuroprotection in an in vitro model of hypoxia-ischemia. 

PMID- 24323732
TI  - Inflammation and cerebral aneurysms.
AB  - Cerebral aneurysms (CAs) occur in up to 5% of the population in the US, and up to
      7% of all strokes are caused by CA rupture. Little is known about the
      pathophysiology of cerebral aneurysm formation, though inflammatory cells such as
      macrophages and neutrophils have been found in the walls of CAs. After many
      studies of both human specimens and experimentally induced animal models of
      aneurysms, the predominant model for CA formation and progression is as follows:
      (1) endothelial damage and degeneration of the elastic lamina, (2) inflammatory
      cell recruitment and infiltration, (3) and chronic remodeling of vascular wall.
      Endothelial damage can be caused by changes in hemodynamic stress, which results
      in the upregulation of proinflammatory cytokine secretion followed by the
      recruitment of various inflammatory cells. This recruitment and subsequent
      infiltration induces smooth muscle cell proliferation, apoptosis, and remodeling
      of the artery wall. These complex events are thought to lead to aneurysm rupture.
      This review will focus on the role of the immune system in the formation and
      progression of saccular CA and the ways in which the immune response may be
      modulated to treat aneurysms and prevent rupture.

PMID- 24323734
TI  - Assessment of template-based protein structure predictions in CASP10.
AB  - Template-based modeling (TBM) is a major component of the critical assessment of
      protein structure prediction (CASP). In CASP10, some 41,740 predicted models
      submitted by 150 predictor groups were assessed as TBM predictions. The accuracy
      of protein structure prediction was assessed by geometric comparison with
      experimental X-ray crystal and NMR structures using a composite score that
      included both global alignment metrics and distance-matrix-based metrics. These
      included GDT-HA and GDC-all global alignment scores, and the superimposition
      independent LDDT distance-matrix-based score. In addition, a superimposition
      independent RPF metric, similar to that described previously for comparing
      protein models against experimental NMR data, was used for comparing predicted
      protein structure models against experimental protein structures. To score well
      on all four of these metrics, models must feature accurate predictions of both
      backbone and side-chain conformations. Performance rankings were determined
      independently for server and the combined server plus human-curated predictor
      groups. Final rankings were made using paired head-to-head Student's t-test
      analysis of raw metric scores among the top 25 performing groups in each
      category.

PMID- 24323735
TI  - The Witkop cyclization: a photoinduced C-H activation of the indole system.
AB  - Investigations of excited-state redox processes have an exceptional impact on the
      field of organic photochemistry and its application to the synthesis of complex
      target molecules. In such a photochemical process a single-electron transfer
      takes place to produce ion-radical intermediates, if the reduction and oxidation
      potentials, as well as excited-state energies of electron donors and acceptors
      are chosen appropriately. The Witkop cyclization constitutes an intramolecular
      variant of such a process, typically with an indole heterocycle as an electron
      donor. The specific synthetic value of this reaction lies in a C?C bond formation
      without requiring any prefunctionalization of the indole system. Although this
      photoreaction has been applied to the total synthesis of natural products, it has
      still not been used to its full capacity. The following review details synthetic
      efforts using the Witkop cyclization, and aims to incite further applications of
      reaction in the synthesis of complex molecular architectures. 

PMID- 24323733
TI  - Ionic regulation of cell volume changes and cell death after ischemic stroke.
AB  - Stroke is a leading cause of human death and disability in the USA and around the
      world. Shortly after the cerebral ischemia, cell swelling is the earliest
      morphological change in injured neuronal, glial, and endothelial cells. Cytotoxic
      swelling directly results from increased Na(+) (with H2O) and Ca(2+) influx into
      cells via ionic mechanisms evoked by membrane depolarization and a number of
      harmful factors such as glutamate accumulation and the production of oxygen
      reactive species. During the sub-acute and chronic phases after ischemia, injured
      cells may show a phenotype of cell shrinkage due to complex processes involving
      membrane receptors/channels and programmed cell death signals. This review will
      introduce some progress in the understanding of the regulation of pathological
      cell volume changes and the involved receptors and channels, including NMDA and
      AMPA receptors, acid-sensing ion channels, hemichannels, transient receptor
      potential channels, and KCNQ channels. Moreover, accumulating evidence supports a
      key role of energy deficiency and dysfunction of Na(+)/K(+)-ATPase in ischemia
      induced cell volume changes and cell death. Specifically, the Na(+) pump failure
      is a prerequisite for disruption of ionic homeostasis including a pro-apoptotic
      disruption of the K(+) homeostasis. Finally, we will introduce the concept of
      hybrid cell death as a result of the Na(+) pump failure in cultured cells and the
      ischemic brain. The goal of this review is to outline recent understanding of the
      ionic mechanism of ischemic cytotoxicity and suggest innovative ideas for future
      translational research. 

PMID- 24323737
TI  - Localization of nickel in tissues of Streptanthus polygaloides Gray (Cruciferae)
      and endemic nickel hyperaccumulators from California.
AB  - The genus Streptanthus Nutt. is one of the most important indicators of
      ultramafic floras in western North America. This genus contains taxa that are
      endemic or tolerant of ultramafic soils. Streptanthus polygaloides is an annual
      nickel hyperaccumulator strictly confined to ultramafic soils throughout the
      Californian Sierra Nevada foothills. Nickel concentration in S. polygaloides
      populations was evaluated by elemental microanalysis using inductively coupled
      plasma mass spectrometry (ICP-MS). Representative samples of S. polygaloides
      roots, stems, leaves, flowers, and fruits were studied by scanning electron
      microscopy (SEM) coupled to an energy-dispersive X-ray probe (SEM-EDX). Results
      show Ni accumulation values between 0.09 and 1.18 %, and a distribution pattern
      similar to that observed in other Ni hyperaccumulator taxa, with the leaf
      epidermis accumulating the largest concentrations. 

PMID- 24323738
TI  - Challenges in multislice computed tomography based fractional flow reserve to
      evaluate interventional treatment.

PMID- 24323736
TI  - 2D:4D ratio in children at familial high-risk for eating disorders: The role of
      prenatal testosterone exposure.
AB  - OBJECTIVES: Markers of prenatal hormone exposure have been associated with the
      development of eating disorder (ED) behaviors. Our aim was to determine whether
      2D:4D ratio, a marker for in utero testosterone exposure, is associated with risk
      for ED in a large population-based cohort: the Avon Longitudinal Study of Parents
      and Children (ALSPAC). METHODS: This is the first study to investigate prenatal
      testosterone exposure in children at high-risk for ED, using 2D:4D as a marker.
      We compared children whose mothers reported a lifetime ED (anorexia, bulimia, or
      both; N = 446) to children whose mothers did not (n = 5,367). RESULTS: Daughters
      of women with lifetime bulimia nervosa (BN) had lower 2D:4D ratio (B: -0.01, 95%
      CI: -0.02 to -0.002, P = 0.02), indicating higher prenatal testosterone exposure,
      than daughters of mothers unaffected by ED. No differences were observed in the
      male children of women with an ED. CONCLUSIONS: Findings suggest that children at
      high-risk for BN may be exposed to higher levels of testosterone in utero. Fetal
      exposure to androgen excess is thought to be causal in the development of
      polycystic ovary syndrome (PCOS), a disorder which is highly comorbid with binge
      eating and BN. Future research should investigate the potential role of
      testosterone exposure in utero as a risk factor for BN and binge eating.

PMID- 24323740
TI  - Preoperative predictable factors for the occurrence of adjacent segment
      degeneration requiring second operation after spinal fusion at isolated L4-L5
      level.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: The purpose of this study was to
      clarify (1) the overall prevalence of radiologic and clinical adjacent segment
      disease (ASD), (2) the prevalence of radiologic ASD at cranial versus caudal
      adjacent segments, and (3) preoperative risk factors and preoperative radiologic
      features associated with radiologic disc degeneration of the cranial and caudal
      adjacent segments. METHODS: A total of 154 patients who underwent posterior
      lumbar interbody fusion and screw-rod fixation at the L4-L5 level were
      retrospectively evaluated more than 2 years after surgery. We analyzed
      demographic factors and radiographic features. Special focus was preoperative
      radiographic features of patients who required additional surgery. These patients
      were studied to detect risk factors for clinical deterioration. RESULTS: Of 154
      patients, 103 (66.8%) showed radiologic degeneration at an adjacent segment after
      surgery-92 (59.7%) at the cranial adjacent segment and 61 (39.6%) at the caudal
      adjacent segment-and 10 patients (6.4%) required second operation because of
      radicular pain as well as severe back pain or spinal instability with back pain
      and neurologic deficits. Age, body mass index (BMI), and preexisting stenosis at
      the cranial adjacent segment were identified as important risk factors for
      clinical ASD requiring second operation. CONCLUSION: Age, BMI, and preexisting
      stenosis at the cranial adjacent segment were the most important risk factors for
      clinical ASD requiring a second operation. Careful consideration is warranted
      when these risk factors are present.

PMID- 24323739
TI  - Visual adaptation of the perception of "life": animacy is a basic perceptual
      dimension of faces.
AB  - One critical component of understanding another's mind is the perception of
      "life" in a face. However, little is known about the cognitive and neural
      mechanisms underlying this perception of animacy. Here, using a visual adaptation
      paradigm, we ask whether face animacy is (1) a basic dimension of face perception
      and (2) supported by a common neural mechanism across distinct face categories
      defined by age and species. Observers rated the perceived animacy of adult human
      faces before and after adaptation to (1) adult faces, (2) child faces, and (3)
      dog faces. When testing the perception of animacy in human faces, we found
      significant adaptation to both adult and child faces, but not dog faces. We did,
      however, find significant adaptation when morphed dog images and dog adaptors
      were used. Thus, animacy perception in faces appears to be a basic dimension of
      face perception that is species specific but not constrained by age categories. 

PMID- 24323741
TI  - Thumbs down: a molecular-morphogenetic approach to avian digit homology.
AB  - Avian forelimb digit homology remains one of the standard themes in comparative
      biology and EvoDevo research. In order to resolve the apparent contradictions
      between embryological and paleontological evidence a variety of hypotheses have
      been presented in recent years. The proposals range from excluding birds from the
      dinosaur clade, to assignments of homology by different criteria, or even
      assuming a hexadactyl tetrapod limb ground state. At present two approaches
      prevail: the frame shift hypothesis and the pyramid reduction hypothesis. While
      the former postulates a homeotic shift of digit identities, the latter argues for
      a gradual bilateral reduction of phalanges and digits. Here we present a new
      model that integrates elements from both hypotheses with the existing
      experimental and fossil evidence. We start from the main feature common to both
      earlier concepts, the initiating ontogenetic event: reduction and loss of the
      anterior-most digit. It is proposed that a concerted mechanism of molecular
      regulation and developmental mechanics is capable of shifting the boundaries of
      hoxD expression in embryonic forelimb buds as well as changing the digit
      phenotypes. Based on a distinction between positional (topological) and
      compositional (phenotypic) homology criteria, we argue that the identity of the
      avian digits is II, III, IV, despite a partially altered phenotype. Finally, we
      introduce an alternative digit reduction scheme that reconciles the current
      fossil evidence with the presented molecular-morphogenetic model. Our approach
      identifies specific experiments that allow to test whether gene expression can be
      shifted and digit phenotypes can be altered by induced digit loss or digit gain.

PMID- 24323742
TI  - Commitment to nutritional endoderm in Eleutherodactylus coqui involves altered
      nodal signaling and global transcriptional repression.
AB  - The vegetal cells of a Xenopus laevis embryo commit to mesendoderm via the Nodal
      signaling pathway. In the direct developing frog Eleutherodactylus coqui,
      mesendoderm is specified at the marginal zone of the early gastrula, and vegetal
      core cells transform into nutritional endoderm. Nutritional endoderm, a novel
      tissue, consists of transient, yolky cells that provide nutrition but remain
      undifferentiated. We report a dual regulation for the generation of nutritional
      endoderm. First, differential expressions of the Nodal-signal transducers Smad2
      and Smad4 were observed during early gastrulation between the marginal zone and
      the vegetal core cells. Although EcSmad2 RNA as well as total and activated Smad2
      protein were detected in the vegetal core, Smad4 protein was expressed less in
      vegetal core during early gastrulation. Only 12% and 50% of vegetal core cells
      were positive for nuclear Smad2 and Smad4 signals respectively compared to 100%
      of marginal zone cells. These results suggest a signaling disruption in the
      vegetal core. Second, vegetal core cells were transcriptionally repressed. At the
      blastula stage, both marginal zone and vegetal core cells were transcriptionally
      silent, but during early gastrulation, only marginal zone cells became
      transcriptionally active. This indicates the occurrence of a mid-blastula
      transition in the marginal zone by early gastrulation, but global transcriptional
      repression persisted in the vegetal core and its derivative, nutritional
      endoderm, throughout development. We have described a novel mechanism, which
      prevents differentiation of the vegetal core through differential Nodal-signaling
      and global transcriptional repression.

PMID- 24323743
TI  - Embryonic yolk removal affects a suite of larval salamander life history traits.
AB  - Egg size is a key life history trait affecting fitness, and it varies abundantly.
      The value of egg size to a mother and her offspring is often determined by a
      trade-off between investing more yolk in a few large eggs or less yolk into many
      more, smaller eggs. Smaller eggs are generally expected to be phenotypically
      inferior or females could increase their fitness by making more smaller eggs.
      However, many females produce a mix of egg sizes and natural yolk variation
      induces normal developmental responses which may persist into subsequent stages
      of a complex life history. Since sources of phenotypic variation are easily
      confounded, I surgically removed yolk from embryonic spotted salamanders
      (Ambystoma maculatum) using a sham surgery as a control and a split-clutch design
      to isolate the effects of yolk reserve variation from genetic sources of
      variation. Yolk removal induced early hatching, reduced developmental stage and
      hatchling body size. Small hatchlings stayed relatively small through the early
      larval period, but 17 weeks later the correlation with early larval body size was
      lost. When the experiment ended, larger individuals were further along in
      metamorphic development but mortality was independent of early larval body size.
      Variation in spotted salamander yolk reserves affects a suite of hatchling life
      history traits that persists into the larval period. Outside the laboratory, egg
      size effects may cascade throughout complex amphibian life histories. Applied
      experimentally and comparatively, this simple yolk removal technique may help
      identify how traits increase or decrease their response to maternal yolk
      investment.

PMID- 24323744
TI  - Safe patient handling and movement: a literature review.
AB  - PURPOSE: Musculoskeletal disorders (MSD) as a result of patient handling tasks
      occur at high rates for nursing staff and other patient care providers. Patient
      care providers perform high-risk patient handling tasks including lifting,
      transferring, ambulating, and repositioning patients. Continuous performance of
      these tasks places a patient care provider at risk for development of a MSD. MSDs
      affect a healthcare organization financially and impact the core of a hospital
      the health of the workforce. The purpose of this research was to study the impact
      of a safe patient handling and movement program on healthcare worker injury,
      costs and job satisfaction. METHODS: A critical review of the safe patient
      handling literature was conducted. FINDINGS: A safe patient handling and movement
      (SPHM) program decreases overall work injury costs and improves healthcare worker
      job satisfaction. CONCLUSIONS AND CLINICAL RELEVANCE: Reduced work injuries,
      decreased injury costs, improved patient outcomes validated in research and
      employees feeling the support of their employer all contribute to a program that
      moves an organization toward a culture of safety.

PMID- 24323746
TI  - Advances in lanthanide-based luminescent peptide probes for monitoring the
      activity of kinase and phosphatase.
AB  - Signaling pathways based on protein phosphorylation and dephosphorylation play
      critical roles in the orchestration of complex biochemical events and form the
      core of most signaling pathways in cells (i.e. cell cycle regulation, cell
      motility, apoptosis, etc.). The understanding of these complex signaling networks
      is based largely on the biochemical study of their components, i.e. kinases and
      phosphatases. The development of luminescent sensors for monitoring kinase and
      phosphatase activity is therefore an active field of research. Examples in the
      literature usually rely on the modulation of the fluorescence emission of organic
      fluorophores. However, given the exceptional photophysical properties of
      lanthanide ions, there is an increased interest in their application as emissive
      species for monitoring kinase and phosphatase activity. This review summarizes
      the advances in the development of lanthanide-based luminescent peptide sensors
      as tools for the study of kinases and phosphatases and provides a critical
      description of current examples and synthetic approaches to understand these
      lanthanide-based luminescent peptide sensors. 

PMID- 24323747
TI  - Electrocardiographically gated 11C-hydroxyephedrine PET for the simultaneous
      assessment of cardiac sympathetic and contractile functions.
AB  - OBJECTIVE: Application of the electrocardiographically (ECG) gated positron
      emission tomography (PET) technique with (11)C-hydroxyephedrine (HED) would allow
      the simultaneous assessment of cardiac sympathetic and contractile functions.
      However, there are uncertainties regarding the diagnostic accuracy of left
      ventricular (LV) volume measurements using ECG-gated HED-PET. The purpose of this
      study was to clarify the minimal requirement of count statistics to measure LV
      volumes with ECG-gated HED-PET and to investigate the reliability of the
      measurements. METHODS: Five healthy volunteers and 11 patients with heart failure
      underwent a 40-min list-mode PET scan after an injection of HED (197 +/- 35 MBq).
      The list-mode data were histogrammed into multiple sets of acquisition periods at
      0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 Mcount/bin and reconstructed into
      corresponding gated images using an iterative algorithm. The LV end-diastolic
      volume (LVEDV), the LV end-systolic volume (LVESV), and the LV ejection fraction
      (LVEF) were calculated in each acquisition period. These values were compared
      with those obtained by cardiac magnetic resonance imaging (MRI). Possible effects
      of HED retention on the accuracy of the volume measurements were investigated.
      RESULTS: Collecting less than 4.0 Mcount/bin resulted in noisy cardiac images.
      The lower counts resulted in underestimation in the volume measurements.
      Reasonably accurate volume measurements required equal to or greater than 6.0
      Mcount/bin. This corresponded to 7.0 +/- 1.9 min (range, 4.0-10.3 min) for the
      acquisition period. Volumetric results using the 6.0 Mcount/bin data highly
      correlated with cardiac MRI (LVEDV: r = 0.85, p < 0.0001; LVESV: r = 0.89, p <
      0.0001; LVEF: r = 0.77, p < 0.01). The HED retention did not affect the
      volumetric results compared to the MRI volumetry. CONCLUSIONS: The volumetric
      accuracy with ECG-gated HED-PET was affected by the count statistics rather than
      the HED retention. LV volume measurements were feasible with 10-min acquisition
      period for most of the patients. This technique allows the simultaneous
      assessment of cardiac sympathetic and contractile functions without the need for
      an additional injection or scanning time, thus reducing overall costs for
      diagnostic imaging.

PMID- 24323748
TI  - Enantioselective disposition of clenbuterol in rats.
AB  - Clenbuterol is a long-acting beta2-adrenoceptor agonist and bronchodilator that
      is used for the treatment of asthma, but the desired activities reside almost
      exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in
      the disposition of clenbuterol following administration of clenbuterol racemate
      to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were
      determined by LC-MS/MS assay with a Chirobiotic T column. This method was
      confirmed to show high sensitivity, specificity and precision, and clenbuterol
      enantiomers in 0.1 ml volumes of plasma were precisely quantified at
      concentrations as low as 0.25 ng/ml. The pharmacokinetic profiles of clenbuterol
      enantiomers following intravenous and intraduodenal administration of clenbuterol
      racemate (2 mg/kg) in rats were significantly different. The distribution volume
      of (-)-R-clenbuterol (9.17 l/kg) was significantly higher than that of (+)-S
      clenbuterol (4.14 l/kg). The total body clearance of (-)-R-clenbuterol (13.5
      ml/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5
      ml/min/kg). An in situ absorption study in jejunal loops showed no difference in
      the residual amount between the (-)-R- and (+)-S-enantiomers. Urinary clearance
      was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol
      was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein
      bound) (-)-R- and (+)-S-clenbuterol in rat plasma were 48.8% and 33.1%,
      respectively. These results indicated that there are differences in the
      distribution and excretion of the clenbuterol enantiomers, and these may be
      predominantly due to enantioselective protein binding.

PMID- 24323745
TI  - Epigenetic regulation: the interface between prenatal and early-life exposure and
      asthma susceptibility.
AB  - Asthma is a complex disease with genetic and environmental influences and
      emerging evidence suggests that epigenetic regulation is also a major
      contributor. Here, we focus on the developing paradigm that epigenetic
      dysregulation in asthma and allergy may start as early as in utero following
      several environmental exposures. We summarize the pathways important to the
      allergic immune response that are epigenetically regulated, the key environmental
      exposures associated with epigenetic changes in asthma genes, and newly
      identified epigenetic biomarkers that have been linked to clinical asthma. We
      conclude with a brief discussion about the potential to apply newly developing
      technologies in epigenetics to the diagnosis and treatment of asthma and allergy.
      The inherent plasticity of epigenetic regulation following environmental
      exposures offers opportunities for prevention using environmental remediation,
      measuring novel biomarkers for early identification of those at risk, and
      applying advances in pharmaco-epigenetics to tailor medical therapies that
      maximize efficacy of treatment. 'Precision Medicine' in asthma and allergy is
      arriving. As the field advances this may involve an individually tailored
      approach to the prevention, early detection, and treatment of disease based on
      the knowledge of an individual's epigenetic profile.

PMID- 24323749
TI  - Recent MRI advances in experimental stroke.

PMID- 24323750
TI  - Neuroimaging of stroke and ischemia in animal models.
AB  - Magnetic resonance imaging (MRI) has dramatically changed our ability to diagnose
      and treat stroke as well as follow its evolution and response to treatment. Early
      stroke and ischemia can be visualized using diffusion-weighted imaging that
      utilizes water diffusion within tissues as a reporter for evolving neuropathology
      that reflects cytotoxic edema, particularly during the first several days after
      injury. T2-weighted imaging is used for evaluation of vasogenic edema but also is
      a reliable indicator of the volume and regional distribution of injured tissues.
      Perfusion-weighted imaging can be used to assess vascular function and also to
      evaluate potential tissues that might be rescued using therapeutic interventions
      (core vs. penumbra). Other imaging modalities such as magnetic resonance
      spectroscopy, diffusion tensor imaging, and susceptibility-weighted imaging are
      also being used to assist in rapid diagnosis of injured tissues following stroke.
      While visual analysis of MR data can provide some information about the evolution
      of injury, quantitative analyses allow definitive and objective evaluations of
      the injury and could be used to assess novel therapeutic strategies. We review
      here the basic uses of neuroimaging, focusing on MR approaches to assess stroke
      and ischemic injury in animal models. 

PMID- 24323752
TI  - Imaging of experimental stroke models.
AB  - The ischemic penumbra is the target of acute stroke therapy. It can be
      approximated on diffusion/perfusion MRI as the ischemic region with abnormal
      perfusion and normal diffusion imaging. Using arterial spin labeling perfusion
      MRI and diffusion MRI, our group has studied the evolution of the
      diffusion/perfusion mismatch in rat stroke models. Additionally, we have
      evaluated the effects of high-flow oxygen on the natural history of penumbral
      evolution, demonstrating that high-flow oxygen "freezes" the evolution of the
      mismatch and allows for later beneficial use of intravenous tissue plasminogen
      activator (tPA). Two neuroprotective drugs, Granulocyte colony stimulating factor
      and a PSD95 inhibitor both impeded the evolution of the mismatch into infarcted
      tissue in vivo and by histological analysis. Employing a novel technique of clot
      imaging, our group was able to demonstrate that the combination of tPA plus
      Annexin-2 was superior to tPA alone in dissolving an embolus and also in reducing
      the extent of hypoperfused brain tissue of perfusion imaging. The use of these
      advanced MRI techniques in animal experiments will help to advance clinical
      imaging of the ischemic penumbra and hopefully contribute to the extension of the
      therapeutic time window in stroke patients. 

PMID- 24323751
TI  - Multimodal MRI of experimental stroke.
AB  - Stroke is the fourth leading cause of death and the leading cause of long-term
      disability in USA. Brain imaging data from experimental stroke models and stroke
      patients have shown that there is often a gradual progression of potentially
      reversible ischemic injury toward infarction. Reestablishing tissue perfusion
      and/or treating with neuroprotective drugs in a timely fashion are expected to
      salvage some ischemic tissues. Diffusion-weighted imaging based on magnetic
      resonance imaging (MRI) in which contrast is based on water motion can detect
      ischemic injury within minutes after onsets, whereas computed tomography and
      other imaging modalities fail to detect stroke injury for at least a few hours.
      Along with quantitative perfusion imaging, the perfusion-diffusion mismatch which
      approximates the ischemic penumbra could be imaged noninvasively. This review
      describes recent progresses in the development and application of multimodal MRI
      and image analysis techniques to study ischemic tissue at risk in experimental
      stroke in rats. 

PMID- 24323753
TI  - MRI stem cell tracking for therapy in experimental cerebral ischemia.
AB  - Magnetic resonance has an established role in investigations on the evolution of
      stroke and the assessment of therapeutic strategies in experimental animals. Here
      we show that the technique has also an important place for the study of stem cell
      mediated regenerative therapies after stroke. We review the literature by
      bridging from the methodological aspects of stem cell labeling via grafting and
      monitoring of cell dynamics after implantation into the brain all the way to
      MRI's role in analyzing the stem cell-mediated functional improvement. Thus, we
      have aimed at a view combining the focus on the monitoring of the cell activities
      with the aspect of lesion evolution while including also the essence of a
      potential functional improvement by the implantation of stem cells following
      stroke. 

PMID- 24323754
TI  - Arterial spin labeling measurements of cerebral perfusion territories in
      experimental ischemic stroke.
AB  - Collateral circulation, defined as the supplementary vascular network that
      maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one
      important defense mechanism of the brain against ischemic stroke. In the present
      study, continuous arterial spin labeling (CASL) was used to quantify CBF and
      obtain perfusion territory maps of the major cerebral arteries in spontaneously
      hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) controls.
      Results show that both WKY and SHR have complementary, yet significantly
      asymmetric perfusion territories. Right or left dominances were observed in
      territories of the anterior (ACA), middle and posterior cerebral arteries, and
      the thalamic artery. Magnetic resonance angiography showed that some of the
      asymmetries were correlated with variations of the ACA. The leptomeningeal
      circulation perfusing the outer layers of the cortex was observed as well.
      Significant and permanent changes in perfusion territories were obtained after
      temporary occlusion of the right middle cerebral artery in both SHR and WKY,
      regardless of their particular dominance. However, animals with right dominance
      presented a larger volume change of the left perfusion territory (23 +/- 9%) than
      animals with left dominance (7 +/- 5%, P < 0.002). The data suggest that animals
      with contralesional dominance primarily safeguard local CBF values with small
      changes in contralesional perfusion territory, while animals with ipsilesional
      dominance show a reversal of dominance and a substantial increase in
      contralesional perfusion territory. These findings show the usefulness of CASL to
      probe the collateral circulation. 

PMID- 24323755
TI  - Oxygen metabolism in ischemic stroke using magnetic resonance imaging.
AB  - Detecting "at-risk" but potentially salvageable brain tissue, known as the
      ischemic penumbra, is of importance for identifying patients who may benefit from
      thrombolytic or other treatments beyond the currently FDA-approved short
      therapeutic window for tissue plasminogen activator. Since the magnetic resonance
      blood oxygenation level-dependent (BOLD) contrast may provide information
      concerning tissue oxygen metabolism, its utilization in ischemic stroke has been
      explored. The focus of this review is to provide an introduction of several BOLD
      based methods, including susceptibility-weighted imaging, R2 BOLD, R2*, R2',
      MR_OEF, and MR_OMI approaches to assess cerebral oxygenation changes induced by
      ischemia. Specifically, we will review the underlying pathophysiological basis of
      the imaging approaches, followed by a brief introduction of BOLD contrast, and
      finally the applications of BOLD approaches in ischemic stroke. The advantages
      and disadvantages of each method are addressed. In summary, the BOLD-based
      methods are promising for imaging oxygenation in ischemic tissue. Future steps
      would include technical refinement and vigorous validation against another
      independent method, such as positron emission tomography. 

PMID- 24323756
TI  - Multimodal MRI of nonhuman primate stroke.
AB  - Stroke is the fourth leading cause of death. Despite decades of research, no
      neuroprotective drug has proven to be effective clinically. One widely accepted
      view to account for this negative outcome is that the rodent stroke model simply
      does not adequately reflect the complexity of human stroke. Recent failures of
      several high-profile neuroprotective drugs for stroke treatment in phase III
      clinical trials further underscore the importance of developing adequate animal
      models for stroke research. The brain organization and vascular circuitry of
      nonhuman primates (NHPs) are more homologous with humans than the widely used
      rodent for stroke modeling. The Stroke Therapy Academic Industry Roundtable, a
      national committee commissioned by the American Heart Association, recommended
      that clinically relevant NHP stroke models be established for developing and
      assessing neuroprotective drugs. The aim of this article is to review the
      challenges and applications of magnetic resonance imaging studies of NHP stroke
      models. 

PMID- 24323757
TI  - Visualization of the Superparamagnetic Iron Oxide (SPIO)-Labeled Bone Marrow
      Stromal Cells Using a 3.0-T MRI-a Pilot Study for Clinical Testing of
      Neurotransplantation.
AB  - Recent studies have elucidated that transplantation of the bone marrow stromal
      cells (BMSC) has therapeutic potential for the central nervous system (CNS)
      disorders. However, no imaging modalities have been established to track the
      engrafted cells in the CNS in clinical situation. This study aimed to investigate
      the ability of magnetic resonance imaging (MRI) to visualize the BMSC labeled
      with superparamagnetic iron oxide (SPIO). The BMSC of mice were labeled with
      SPIO. Various numbers of the cells were injected into the agar phantom and were
      visualized using a 3.0-T MR apparatus. The SPIO-labeled cells were injected into
      the temperature-sensitive gelation polymer (TGP) hydrogel and were cultured for 7
      days. They were also visualized just after the injection and at 7 days
      postinjection. After a 7-day culture, they were stained with Turnbull blue
      technique. T2-, T2*-, and susceptibility-weighted imaging could identify
      minimally 1,000 cells in the agar or TGP hydrogel, although it was difficult to
      quantify their number on MRI. All of these sequences could track the SPIO-labeled
      BMSC for at least 7 days when injected into the TGP. Turnbull blue staining
      revealed the survival and proliferation of the SPIO-labeled BMSC in the TGP for 7
      days. The findings strongly suggest that the SPIO labeling may enable to track
      minimally 1,000 cells engrafted in the CNS on clinical MR apparatus. These data
      would be valuable to consider the application of imaging technique into cell
      transplantation therapy for CNS disorders. 

PMID- 24323758
TI  - Perfusion Characteristics in Chronic Cerebrovascular Insufficiency : An
      Anatomically and Clinically Oriented XeCT Analysis of Cerebrovascular
      Atherosclerotic Disease.
AB  - Xenon-enhanced computed tomography (XeCT) allows quantification of hemodynamic
      insufficiency in the setting of cerebrovascular atherosclerotic disease (CAD).
      However, data regarding the relationship between hemodynamic indices [cerebral
      blood flow (CBF) and cerebrovascular reserve capacity (CVRC)] and normal subjects
      (with aging) and pathology (progression of CAD or development of stroke symptoms)
      are limited. In this study, we analyzed 103 consecutive patients undergoing XeCT
      according to age, anatomical location and disease severity. We stratified
      anatomically defined ROIs according to a classification system that observes the
      presence of proximal stenosis (class I vs. class II/III) as well as the presence
      of neurological symptoms (class II vs. III); CBF, CVRC and hemodynamic stress
      distribution were calculated. Supratentorial CBF decreases significantly with
      age, but not infratentorially. Cortical CVRC remains stable over time. Our
      classification of disease severity correlated highly significantly with a
      decrease in supratentorial CBF and CVRC, though CVRC is less sensitive to age
      related changes. Regression analysis delineated a CVRC of 34% to discriminate
      between ROI classes. Age-dependent perfusion characteristics in normal vascular
      territories were characterized. In CAD, CVRC remains the most sensitive
      parameter. A simplified classification of ROIs according to disease severity
      correlates well with established markers for hemodynamic insufficiency. It may
      facilitate comparison of different pathologies such as CAD and Moyamoya disease
      and will be the focus of further studies. 

PMID- 24323759
TI  - Proteasome Inhibitor Reduces Astrocytic iNOS Expression and Functional Deficit
      after Experimental Intracerebral Hemorrhage in Rats.
AB  - Intracerebral hemorrhage (ICH) is associated with perihematoma inflammation and
      edema. We have recently shown cell death and a robust activation of the
      proinflammatory transcription factor, nuclear factor-kappaB (NF-kappaB) in brain
      areas adjacent to the hematoma. Proteasome represents a key component necessary
      for the activation of NF-kappaB. The aim of our present study was to examine if
      selective proteasome inhibition with a clinically relevant agent, PS-519, might
      influence the ICH pathogenesis, and improve functional outcome. ICH was induced
      in Sprague-Dawley rats by the double blood injection method. PS-519 was
      administered intravenously 4 h and 15 min after induction of ICH. Behavioral
      testing was performed 3, 5, and 7 days later. The animals were sacrificed on day
      7, and their brains were evaluated for hemorrhage size and inflammation using
      immunohistochemistry with antibody to various inflammatory markers. Treatment
      with PS-519 significantly (p < 0.05) reduced behavioral impairment post-ICH as
      determined by the footfault test. This effect was not due to difference in ICH
      volume. The improved functional status of PS-519 treated animals correlated
      positively (p < 0.01) with reduced expression of astroglial iNOS in areas
      adjacent to the hemorrhage 7 days post-ICH. No delayed changes in expression of
      OX-42 and ED-1 (microglia/macrophages marker), or vimentin (intermediate
      filament; marker of astroglia activation) were detected in animals treated with
      PS-519. This data suggests that modulation of proteasome-activated processes may
      represent a strategic target for treatment of ICH in humans. 

PMID- 24323760
TI  - An Endovascular Perforation Model of Subarachnoid Haemorrhage in Rat Produces
      Heterogeneous Infarcts that Increase with Blood Load.
AB  - Subarachnoid haemorrhage (SAH) is a devastating disease and a major burden on
      society. Despite this, pharmacological treatment options are limited. Appropriate
      animal modelling of SAH is essential for the development of neuroprotective
      drugs, but experimental SAH often fails to produce widespread neuronal loss, as
      frequently seen in humans. We report that a recently described modification of
      the endovascular perforation model in rat produced widespread heterogeneous
      infarcts 72 h after SAH. Cerebral blood flow (CBF) was monitored, with or without
      intracranial pressure (ICP) measurement, for 1 h after induction of SAH. Blood
      load size was assessed, and brain injury was quantified at 72 h using
      histological staining, blood brain barrier breakdown assessment and
      immunofluorescent imaging of neuronal viability and microglial activation.
      Results showed that ICP measurement allowed for faster recovery of CBF,
      potentially reducing brain injury. Larger subarachnoid blood loads predicted more
      extensive neuronal damage which was easily quantified with the combination of
      histological and immunohistochemical techniques. Thus, for the investigation of
      neuroprotective strategies after SAH, the present protocol produces quantifiable,
      clinically relevant, heterogeneous patterns of infarct due to large blood loads,
      high ICP and low CBF. 

PMID- 24323761
TI  - A d(10) Ni-(H(2)) adduct as an intermediate in H-H oxidative addition across a Ni
      B bond.
AB  - Bifunctional E?H activation offers a promising approach for the design of two
      electron-reduction catalysts with late first-row metals, such as Ni. To this end,
      we have been pursuing H2 activation reactions at late-metal boratranes and herein
      describe a diphosphine-borane-supported Ni-(H2 ) complex, [((Ph) DPB(iPr) )Ni(H2
      )], which has been characterized in solution. (1) H NMR spectroscopy confirms the
      presence of an intact H2 ligand. A range of data, including electronic-structure
      calculations, suggests a d(10) configuration for [((Ph) DPB(iPr) )Ni(H2 )] as
      most appropriate. Such a configuration is highly unusual among transition-metal
      H2 adducts. The nonclassical H2 adduct is an intermediate in the complete
      activation of H2 across the Ni?B interaction. Reaction-coordinate analysis
      suggests synergistic activation of the H2 ligand by both the Ni and B centers of
      the nickel boratrane subunit, thus highlighting an important role of the borane
      ligand both in stabilizing the d(10) Ni-(H2 ) interaction and in the H-H cleavage
      step. 

PMID- 24323762
TI  - FGFR1 signaling is associated with the magnitude of morphological integration in
      human head shape.
AB  - OBJECTIVES: The head can be used as a model to study complex phenotypes
      controlled simultaneously by morphological integration (MI) due to common
      factors, and modular patterns caused by local factors affecting the development
      and functional demands of specific structures. The fibroblast growth factor and
      receptor system (FGF/FGFR) participates in cell communication and pattern
      formation in osseous tissues, among others, and there is compelling evidence from
      mouse model studies suggesting a role of the FGF/FGFR pathway as a covariance
      generating signaling process in head development. Here we use human data to test
      if specific genetic variants of another gene of this pathway, the FGFR1 gene, can
      be associated with differences in the integration of the head. METHODS: We
      explored whether and how three specific variants on FGFR1, previously associated
      with human cephalic index, influence the pattern and level of head integration of
      one Native American and one admixed group from Mexico. MI, measured as the
      intensity of covariation among head traits, was assessed using data from three
      dimensional head landmark coordinates taken on 176 individuals. RESULTS:
      Individuals carrying the derived allele of the rs4647905:G>C polymorphism present
      significantly greater levels of head MI, especially in facial structures and on
      the shape space where the modular portion of the covariation is explicitly
      removed. CONCLUSIONS: Since FGFR genes present nonconservative and tissue
      specific splicing sites, they may have some effect on protein structure and
      performance likely involved in developmental processes responsible for the
      magnitude and pattern of MI in the human head.

PMID- 24323763
TI  - Mechano growth factor E peptide regulates migration and differentiation of bone
      marrow mesenchymal stem cells.
AB  - IGF1Ec in humans or IGF1Eb in rodents (known as mechano growth factor (MGF)) has
      a unique E domain, and the C-terminal end of the E domain (MGF E peptide) plays
      important roles in proliferation, migration and differentiation of many cell
      types. Bone marrow mesenchymal stem cells (BMSCs) have multiple differentiation
      potentials and are considered as perfect seed cells for tissue repair. But the
      role of MGF E peptide on BMSCs is seldom investigated and the mechanism is still
      unclear. In this study, we investigated the effects of MGF E peptide on rat BMSCs
      (rBMSCs). Our results revealed that treatment with MGF E peptide had no effect on
      BMSC proliferation. However, both wound-healing and transwell assays indicated
      that MGF E peptide could significantly enhance rBMSCs migration ability. Further
      analysis indicated that MGF E peptide also reduced the expression levels of
      osteogenic genes, but increased the expression levels of adipogenic genes.
      Analysis of molecular mechanism showed that phosphorylation-Erk1/2 was activated
      by MGF E peptide and blockage of either Erk1/2 or IGF1 receptor could repress the
      migration effect of MGF E peptide. In conclusion, MGF E peptide is able to
      inhibit osteogenic differentiation but promote adipogenic differentiation. In
      addition, the migration effect of MGF E peptide on rBMSCs depends on IGF1
      receptor via Erk1/2 signal pathway. 

PMID- 24323764
TI  - Safety and efficacy of the MitraClip(r) system for severe mitral regurgitation: a
      systematic review.
AB  - BACKGROUND: The MitraClip(r) system is a newer percutaneous device that has shown
      promising results but data on its safety and efficacy in low- and high-surgical
      risk populations continues to evolve. We performed a systematic review of the
      published studies reporting the safety and efficacy of MitraClip(r) implantation
      for treatment of moderate to severe and severe mitral regurgitation (MR).
      METHODS: Reviewers independently searched for relevant articles in Medline and
      abstracted clinical information based on pre-defined criteria and end-points.
      Patients were classified as low- or high-surgical risk for conventional mitral
      valve (MV) surgery based on Society of Thoracic Surgeons score, EuroSCORE, or
      surgeon discretion. Primary safety outcome was 30-day mortality and primary
      efficacy outcomes were freedom from death, >=3+ MR, and requirement for MV
      surgery during follow-up. RESULTS: Immediate and long-term outcomes of 16
      studies, including 2980 patients (age 73.7 +/- 0.6 years; 63.3% males) receiving
      the MitraClip(r), were analyzed. Acute procedural success rate was 91.4% with a
      procedural mortality of 0.1%. Mortality at 30 days and long-term (310 days)
      follow-up was 4.2 and 15.8%, respectively and was significantly higher in the
      high-risk group (P = 0.003 and 0.019, respectively). Incidence of major
      procedural adverse outcomes was relatively low with blood transfusion accounting
      for most events. At follow-up, the number of patients with >=3+ MR reduced from
      96.3% to 14.7% (P < 0.001), and those with NYHA class III/IV reduced from 83.2%
      to 23.4% (P < 0.001). CONCLUSION: MitraClip(r) implantation for moderate to
      severe or severe MR appears to be safe with a very low procedural mortality.
      There is significant improvement in functional outcomes although long-term
      mortality is high, especially in high surgical risk patients.

PMID- 24323765
TI  - Carnosol, rosemary ingredient, induces apoptosis in adult T-cell
      leukemia/lymphoma cells via glutathione depletion: proteomic approach using
      fluorescent two-dimensional differential gel electrophoresis.
AB  - Adult T-cell leukemia/lymphoma (ATL) is a fatal malignancy caused by infection
      with human T-lymphotropic virus type-1 and there is no accepted curative therapy
      for ATL. We searched for biological active substances for the prevention and
      treatment of ATL from several species of herbs. The ATL cell growth-inhibitory
      activity and apoptosis assay showed that carnosol, which is an ingredient
      contained in rosemary (Rosmarinus officinalis), induced apoptosis in ATL cells.
      Next, to investigate the apoptosis-inducing mechanism of carnosol, we applied
      proteomic analysis using fluorescent two-dimensional differential gel
      electrophoresis and mass spectrometry. The proteomic analysis showed that the
      expression of reductases, enzymes in glycolytic pathway, and enzymes in pentose
      phosphate pathway was increased in carnosol-treated cells, compared with
      untreated cells. These results suggested that carnosol affected the redox status
      in the cells. Further, the quantitative analysis of glutathione, which plays the
      central role for the maintenance of intracellular redox status, indicated that
      carnosol caused the decrease of glutathione in the cells. Further, N-acetyl-L
      cystein, which is precursor of glutathione, canceled the efficiency of carnosol.
      From these results, it was suggested that the apoptosis-inducing activity of
      carnosol in ATL cells was caused by the depletion of glutathione. 

PMID- 24323766
TI  - Divergent palate morphology in turtles and birds correlates with differences in
      proliferation and BMP2 expression during embryonic development.
AB  - During embryonic development, amniotes typically form outgrowths from the medial
      sides of the maxillary prominences called palatal shelves or palatine processes.
      In mammals the shelves fuse in the midline and form a bony hard palate that
      completely separates the nasal and oral cavities. In birds and lizards, palatine
      processes develop but remain unfused, leaving a natural cleft. Adult turtles do
      not possess palatine processes and unlike other amniotes, the internal nares open
      into the oral cavity. Here we investigate craniofacial ontogeny in the turtle,
      Emydura subglobosa to determine whether vestigial palatine processes develop and
      subsequently regress, or whether development fails entirely. We found that the
      primary palate in turtles develops similarly to other amniotes, but secondary
      palate ontogeny diverges. Using histology, cellular dynamics and in situ
      hybridization we found no evidence of palatine process development at any time
      during ontogeny of the face in the turtle. Furthermore, detailed comparisons with
      chicken embryos (the model organism most closely related to turtles from a
      molecular phylogeny perspective), we identified differences in proliferation and
      gene expression patterns that correlate with the differences in palate
      morphology. We propose that, in turtles, palatine process outgrowth is never
      initiated due to a lack of mesenchymal bone morphogenetic protein 2 (BMP2)
      expression in the maxillary mesenchyme, which in turn fails to induce the
      relatively higher cellular proliferation required for medial tissue outgrowth. It
      is likely that these differences between turtles and birds arose after the
      divergence of the lineage leading to modern turtles.

PMID- 24323767
TI  - Differential impact of types of social support in the mental health of formerly
      incarcerated Latino men.
AB  - The role of social support in the mental health of formerly incarcerated Latino
      men (FILM) is an issue overlooked in public health prevention efforts. The
      objectives of this analysis were to (a) describe the levels of social support
      perceived and received by FILM; (b) identify the associations, if any, between
      levels of social support and mental health indicators such as depression and
      anxiety; and (c) explore the impact of familism and hypermasculinity on the
      receptivity of social support and the potential role of these factors in
      mediating associations between social support and mental health indicators. To
      accomplish the objectives, we conducted a cross-sectional survey with FILM (n =
      259), ages 18 to 59, in New York City, and one nominated member of their social
      network (n = 130 dyads). In this analysis, we examined four dimensions of social
      support (instrumental, informational, appraisal, and emotional) from two
      perspectives: provided (as reported by members of the social networks) and
      perceived (as reported by FILM). The major outcome variables for this analysis
      were the presence/absence of major anxiety and depressive symptoms. Our logistic
      regression analyses suggest that perceived emotional support was inversely
      associated with both anxiety and depression. Our findings suggest that familism
      mediated the association between perceived emotional support and
      anxiety/depression. Therefore, we must consider designing network enhancement
      interventions that focus on both FILM and their social support systems.

PMID- 24323768
TI  - Psychological gender of men with systolic heart failure: a neglected strategy to
      cope with the disease?
AB  - Diminished exercise capacity is a fundamental symptom of heart failure (HF),
      which is particularly disadvantageous for men for whom exercise capacity
      contributes significantly to their gender identity, self-esteem, and quality of
      life. In this study, we aimed to examine whether psychological gender would be
      different in men with systolic HF as compared with their healthy peers. The
      authors examined 48 men with systolic HF (age = 64 +/- 10 years; body mass index
      = 28.3 +/- 3.4 kg/m(2); NYHA I/II/III [%] = 25/65/10; left ventricular ejection
      fraction [LVEF] = 32.1 +/- 7.8%) and 15 age-matched healthy men. Based on the
      results of the Polish version of the Bem Sex Role Inventory, the examined men
      were divided into four types of psychological gender: "masculine" (M), "feminine"
      (F), "unspecified" (U), and "androgynous" (A). None of the men with HF presented
      M type of psychological gender, whereas this type was found in 27% of the healthy
      men (p = .0002). The prevalence of both A (38% vs. 47%) and F (10% vs. 20%, both
      p > .05) types of psychological gender was similar between men with HF versus
      without HF. More men with HF fulfilled the criteria of the U type of
      psychological gender as compared with healthy peers (51% vs. 7%, p = .002). Men
      with HF and the F type of psychological gender were treated with spironolactone
      more frequently than those classified with the U and A types (both p < .05). The
      lack of "psychologically masculine" and the overrepresentation of
      "psychologically unspecified" gender types in the HF group suggests that
      psychological gender may be affected among men with HF.

PMID- 24323769
TI  - Membrane-type 1 metalloproteinase is upregulated in microglia/brain macrophages
      in neurodegenerative and neuroinflammatory diseases.
AB  - We previously reported that glioma cells induce the expression of membrane-type 1
      metalloproteinase (MT1-MMP or MMP-14) in tumor-associated microglia/macrophages
      and promote tumor growth, whereas MMP-14 expression in microglia under
      physiological conditions is very low. Here, we show that the increase in MMP-14
      expression is also found in microglia/macrophages associated with
      neurodegenerative and neuroinflammatory pathologies in mouse models as well as in
      human biopsies or post-mortem tissue. We found that microglial/macrophage MMP-14
      expression was upregulated in Alzheimer's disease tissue, in active lesions of
      multiple sclerosis, and in tissue from stage II stroke as well as in the
      corresponding mouse models for the human diseases. In contrast, we observed no
      upregulation for MMP-14 in microglia/macrophages in the early phase of stroke or
      in the corresponding mouse model, in human amyotrophic lateral sclerosis (ALS)
      tissue or in a mouse model of ALS as well as in human cases of acute brain
      trauma. These data indicate that MMP-14 expression is not a general marker for
      activated microglia/macrophages but is upregulated in defined stages of
      neuroinflammatory and neurodegenerative diseases and that there is generally a
      good match between mouse models and human brain pathologies.

PMID- 24323770
TI  - Performance of SEM scintillation detector evaluated by modulation transfer
      function and detective quantum efficiency function.
AB  - In the paper, the SEM detector is evaluated by the modulation transfer function
      (MTF) which expresses the detector's influence on the SEM image contrast. This is
      a novel approach, since the MTF was used previously to describe only the area
      imaging detectors, or whole imaging systems. The measurement technique and
      calculation of the MTF for the SEM detector are presented. In addition, the
      measurement and calculation of the detective quantum efficiency (DQE) as a
      function of the spatial frequency for the SEM detector are described. In this
      technique, the time modulated e-beam is used in order to create well-defined
      input signal for the detector. The MTF and DQE measurements are demonstrated on
      the Everhart-Thornley scintillation detector. This detector was alternated using
      the YAG:Ce, YAP:Ce, and CRY18 single-crystal scintillators. The presented MTF and
      DQE characteristics show good imaging properties of the detectors with the YAP:Ce
      or CRY18 scintillator, especially for a specific type of the e-beam scan. The
      results demonstrate the great benefit of the description of SEM detectors using
      the MTF and DQE. In addition, point-by-point and continual-sweep e-beam scans in
      SEM were discussed and their influence on the image quality was revealed using
      the MTF.

PMID- 24323771
TI  - Editorial.

PMID- 24323772
TI  - Clinical implications of neuroimaging in stroke.

PMID- 24323773
TI  - Perfusion-diffusion mismatch: does it identify who will benefit from reperfusion
      therapy?
AB  - A method to determine which patients would benefit from reperfusion therapies
      after 4.5 h would greatly add to our ability to reduce the disability caused by
      stroke. The goal of magnetic resonance perfusion-diffusion imaging in hyperacute
      ischemic stroke is to identify regions of the brain that will die if untreated
      and will live and regain function if quickly reperfused. The clinical value of
      perfusion-diffusion imaging in hyperacute ischemic stroke can be proven only by
      demonstrating empirically in a randomized controlled trial (RCT) that there is an
      improvement in patient outcome that depends on the use of the neuroimaging
      modality to guide therapy. To date, there have been only a few RCTs that have
      evaluated whether perfusion-diffusion imaging can identify a subgroup of patients
      with ischemic stroke more than 4.5 h from onset in whom the overall benefit from
      reperfusion therapy outweighs the risk. None have met the rigorous design
      requirements of the three-group study necessary to adequately test this
      hypothesis, and none have even met their own criteria for demonstrating a
      clinical benefit. While studies are not sufficient to conclusively disprove the
      hypothesis there are no RCT data to support it, and thus, the clinical value of
      MRI perfusion-diffusion imaging in this setting remains unproven. It is worthy of
      further investigation in rigorously designed RCTs. However, the risks of
      symptomatic intracerebral hemorrhage with reperfusion therapies in acute ischemic
      stroke are proven. Unless RCT data are forthcoming to demonstrate that MRI
      perfusion-diffusion mismatch improves clinical outcome, it should not be used to
      guide delayed reperfusion therapy. 

PMID- 24323774
TI  - Perfusion/Diffusion mismatch is valid and should be used for selecting delayed
      interventions.
AB  - The mismatch between a larger perfusion lesion and smaller diffusion lesion on
      magnetic resonance imaging is a validated signal of the ischemic penumbra, namely
      the region at risk in acute ischemic stroke that is critically hypoperfused and
      the target of reperfusion therapies. Clinical trials have shown strong
      correlations between reperfusion in mismatch patients and improved clinical
      outcomes. Attenuation of infarct growth is associated with reperfusion and
      corresponding clinical gains. Using computed tomography perfusion, the mismatch
      between relative cerebral blood flow or cerebral blood volume and perfusion delay
      is a comparable penumbral marker. Automated techniques allow rapid quantitative
      assessment of mismatch with thresholding to exclude benign oligemia. The penumbra
      is often present beyond the current 4.5-h time window, defined for the use of
      intravenous tPA. Treatment beyond this time point remains investigational.
      Although the efficacy of thrombolysis in mismatch patients requires further
      validation in randomized trials, there is now sufficient evidence to recommend
      that advanced neuroimaging of mismatch should be used for selection of delayed
      therapies in phase 3 trials. 

PMID- 24323775
TI  - Defining the ischemic penumbra using hyperacute neuroimaging: deriving
      quantitative ischemic thresholds.
AB  - Despite three decades of promise, a neuroimaging biomarker capable of delineating
      the ischemic penumbra is yet to be definitively demonstrated. Much progress has
      been made, especially with MR imaging. However, in order to rigorously define an
      imaging biomarker of the ischemic penumbra, carefully designed studies which can
      derive ischemic thresholds using quantitative imaging parameters may be required.
      Two thresholds are of interest: one which distinguishes the ischemic core from
      penumbra, and another which distinguishes the penumbra from benign oligemia. In
      this review, we discuss one possible approach to define these thresholds by
      following tissue fate in the presence or absence of early reperfusion. 

PMID- 24323777
TI  - Standardization of Stroke Perfusion CT for Reperfusion Therapy.
AB  - With the advances in terms of perfusion imaging, the "time is brain" approach
      used for acute reperfusion therapy in ischemic stroke patients is slowly being
      replaced by a "penumbra is brain" or "imaging is brain" approach. But the concept
      of penumbra-guided reperfusion therapy has not been validated. The lack of
      standardization in penumbral imaging is one of the main contributing factors for
      this absence of validation. This article reviews the issues underlying the lack
      of standardization of perfusion-CT for penumbra imaging, and offers avenues to
      remedy this situation. 

PMID- 24323776
TI  - Improving acute stroke management with computed tomography perfusion: a review of
      imaging basics and applications.
AB  - The inclusion of dynamic contrast-enhanced computed tomography (CT) or CT
      perfusion (CTP) scan into the imaging workup for acute stroke patients is
      widespread. Along with vessel occlusion status from CT angiography, CTP provides
      pathophysiological information a non-contrast CT cannot provide during the
      hyperacute stages of cerebral ischemia. Measurement of parenchymal perfusion at
      the capillary level can be used to characterize tissue viability, a target for
      thrombolysis. Further, CTP is useful for the detection of blood brain barrier
      disturbances with the permeability surface area product parameter (PS). Although
      new to stroke imaging, PS has diagnostic and prognostic implications for primary
      hemorrhage and secondary hemorrhagic transformation of ischemic stroke. The
      purpose of this article is to provide an overview of the CTP imaging concepts and
      their uses for imaging in stroke. 

PMID- 24323778
TI  - Arterial spin labeling for acute stroke: practical considerations.
AB  - Arterial spin labeling (ASL) is a non-contrast method of measuring cerebral
      perfusion with MRI. It has several advantages over traditional contrast-based
      perfusion-weighted imaging, including non-invasiveness, more straightforward
      cerebral blood flow (CBF) quantification, and repeatability. However, because of
      its lower signal-to-noise ratio (SNR) per unit time and its high sensitivity to
      arterial transit delays, it has not been used frequently in acute stroke, where
      arterial delays and time-efficiency are of the essence. This is beginning to
      change, driven by higher SNR implementations of ASL and the increasing use of 3T
      scanners. Furthermore, velocity-selective ASL sequences that are largely
      insensitive to arrival times are beginning to be applied to patients with
      cerebrovascular disease and promise the ability to quantify CBF even in regions
      supplied by late-arriving collateral flow. Despite these advances, many practical
      issues must be addressed to optimize ASL for its use in acute stroke studies.
      These include optimizing the trade-off between time, SNR, imaging resolution, and
      sensitivity to slow flow. Rapid and robust post-processing of image data must be
      made routine, such that CBF maps are available in real time so that they can be
      considered when making treatment decisions. Lastly, automated software needs to
      be developed in order to delineate hypoperfused tissue volumes, which is
      challenging due to the inherent differences between gray and white matter CBF.
      Attention to these details is critical to translate this promising research tool
      into mainstream clinical trials and practice in acute stroke. 

PMID- 24323780
TI  - Noninvasive Measurements of Cerebral Blood Flow, Oxygen Extraction Fraction, and
      Oxygen Metabolic Index in Human with Inhalation of Air and Carbogen using
      Magnetic Resonance Imaging.
AB  - Noninvasive magnetic resonance (MR) methods have been explored to provide
      quantitative measurements of cerebral blood flow (CBF), oxygen extraction
      fraction (OEF), and oxygen metabolic index (OMI = CBF * OEF). In this study, we
      sought to evaluate whether MR measured OEF, CBF, and OMI can consistently detect
      the expected physiological changes in humans under normal and hyperoxic
      hypercapnic conditions. Nine healthy human subjects were scanned while breathing
      through a mask, alternating inhaled gas in a sequential order as room air,
      carbogen (3% CO2 mixed with 97% O2), room air, carbogen, and room air. OEF, CBF,
      and OMI were obtained from the whole brain, gray matter (GM), and white matter
      (WM) at each gas inhalation state. Similar to previous positron emission
      tomography findings, our study consistently demonstrated a 10-12% decrease in OEF
      with a 10% increase of CBF and a stable OMI during carbogen inhalation. Moreover,
      GM/WM ratio in CBF and OMI remained constant during air and carbogen breathing.
      In addition, OEF, CBF, and OMI were highly reproducible if the same inhaled gas
      was used. In summary, our results demonstrate that noninvasive MR measurements
      can provide reproducible measurements of OEF, CBF, and OMI in normal subjects
      under normal and altered physiological conditions. 

PMID- 24323779
TI  - Sodium MRI and the assessment of irreversible tissue damage during hyper-acute
      stroke.
AB  - Sodium MRI (sMRI) has undergone a tremendous amount of technical development
      during the last two decades that makes it a suitable tool for the study of human
      pathology in the acute setting within the constraints of a clinical environment.
      The salient role of the sodium ion during impaired ATP production during the
      course of brain ischemia makes sMRI an ideal tool for the study of ischemic
      tissue viability during stroke. In this paper, the current limitations of
      conventional MRI for the determination of tissue viability during evolving brain
      ischemia are discussed. This discussion is followed by a summary of the known
      findings about the dynamics of tissue sodium changes during brain ischemia. A
      mechanistic model for the explanation of these findings is presented together
      with the technical requirements for its investigation using clinical MRI
      scanners. An illustration of the salient features of the technique is also
      presented using a nonhuman primate model of reversible middle cerebral artery
      occlusion. 

PMID- 24323781
TI  - New insights in perinatal arterial ischemic stroke by assessing brain perfusion.
AB  - Perinatal arterial ischemic stroke (AIS) is an important cause of long-term
      morbidity in children. Thus, there is an urgent need to better understand the
      mechanisms of stroke in newborns in order to develop effective treatment and
      prevention strategies. The purpose of this study was to assess brain perfusion
      within the first month of life in newborns with AIS. In this study, magnetic
      resonance imaging (MRI) and perfusion imaging by arterial spin labeling (ASL)
      were used to assess brain perfusion in four term newborns with AIS. One patient
      had a stroke within the territory of the right middle cerebral artery (MCA); the
      other three patients had a stroke within the territory of the left MCA. None of
      them displayed any hemorrhagic component. All four patients demonstrated abnormal
      brain perfusion in the stroke area. Cerebral blood flow (CBF) within the stroke
      area was increased in patient # 1. In all other three patients, CBF was decreased
      within the stroke center and increased in the periphery of the stroke area. These
      results show the feasibility of the ASL sequence in newborns with AIS and support
      its addition to the current MRI protocol used in these newborns as it provides
      useful information on brain hemodynamics. Its value for identifying salvageable
      tissue in newborns needs to be further assessed, as well as its potential role in
      stroke follow-up and for tissue-specific treatment screening. 

PMID- 24323782
TI  - Muscle microdialysis to confirm sublethal ischemia in the induction of remote
      ischemic preconditioning.
AB  - Exposure of one tissue to ischemia-reperfusion confers a systemic protective
      effect, referred to as remote ischemic preconditioning (RIPC). Confirmation that
      the desired effect of ischemia is occurring in tissues used to induce RIPC
      requires an objective demonstration before this technique can be used
      consistently in the clinical practice. Enrolled patients underwent three to four
      RIPC sessions on non-consecutive days. Sessions consisted of 4 cycles of 5 min of
      leg cuff inflation to 30 mmHg above the systolic blood pressure followed by
      reperfusion. Absence of leg pulse was confirmed by Doppler evaluation. To
      evaluate limb transient ischemia, patients were monitored with muscle
      microdialysis. Glucose, lactate, lactate/pyruvate ratio, and glycerol levels were
      measured. Fourteen microdialysis sessions were performed in seven patients
      undergoing RIPC (42.8 % male; mean age, 51.8; Fisher grade 4 in all seven
      patients, Hunt and Hess grade 5 in five patients, four in one patient and one in
      one patient). An average follow-up of 29 days demonstrated no complications
      associated with the procedure. Muscle microdialysis during RIPC sessions showed a
      significant increase in lactate/pyruvate ratio (21.2 to 26.8, p = 0.001) and
      lactate (3.0 to 3.9 mmol/L, p = 0.002), indicating muscle ischemia. There was no
      significant variation in glycerol (234 to 204 MUg/L, p = 0.43), indicating no
      permanent cell damage. The RIPC protocol used in this study is safe, well
      tolerated, and induces transient metabolic changes consistent with sublethal
      ischemia. Muscle microdialysis can be used safely as a confirmatory tool in the
      induction of RIPC. 

PMID- 24323783
TI  - The ABCD(2) Score is Highly Predictive of Stroke in Minor Ischemic Stroke
      Patients.
AB  - Stroke risk prediction scores have been designed to stratify risk of recurrent
      cerebrovascular events in transient ischemic attack (TIA) and minor ischemic
      stroke (MIS) patients. Consecutive TIA or MIS patients referred to Ghaem
      Hospital, Mashhad were enrolled in a prospective cohort study during 2010-2011.
      Only TIA or MIS patients presenting within 24 h from the onset of symptoms were
      recruited. MIS was considered as ischemic stroke with NIHSS <4. The end point of
      the study was a new ischemic cerebrovascular event or vascular death at 90 days
      and additionally at 3 days. The decision to admit and treatment in each case was
      left to the discretion of the stroke neurologist. The predictive accuracy of the
      ABCD(2) scoring system for recurrent stroke or TIA was quantified by the area
      under the cure (AUC) using the c statistics. Three hundred ninety-three TIA
      patients (238 males, 155 females) and 118 MIS patients (77 males, 41 females)
      were enrolled in the study. One hundred seventeen strokes (23.2%), 99 TIA
      (19.6%), and 11 vascular death (2.2%) occurred within 3 months postevent in the
      whole of our 511 patients with minor ischemic events. The ABCD(2) score had a
      weak predictive value for 3 months and 3 days recurrent stroke in our TIA
      patients (AUC = 0.599, AUC = 0.591), but a high predictive value for 3 months and
      3 days recurrent stroke in our MIS patients (AUC = 0.727, AUC = 0.728),
      respectively. The ABCD(2) score is highly predictive of short-term recurrent
      stroke in MIS patients but not TIA cases, despite its creation for TIA cohorts. 

PMID- 24323784
TI  - Effective strategy for managing H7N9 virus infection.

PMID- 24323785
TI  - Diarrheagenic enteroaggregative Escherichia coli causing urinary tract infection
      and bacteremia leading to sepsis.
AB  - We report a case of a 55-year-old immunocompromised female who presented to the
      emergency department with severe diarrhea and vomiting following travel to the
      Philippines. Stool bacteriology revealed a mixed infection involving an
      enteropathogenic Escherichia coli and two distinct strains of enteroaggregative
      Escherichia coli (EAEC). During hospitalization, urine and blood culture tested
      positive for one of the diarrheagenic EAEC strains, necessitating urinary
      catheterization, intensive care, and antimicrobial treatment with trimethoprim
      sulfamethoxazole, followed by meropenem. Although known to occasionally cause
      urinary tract infections, EAEC have not been previously associated with sepsis.
      Our report highlights the potential of EAEC to cause severe extraintestinal
      infections. 

PMID- 24323786
TI  - Chemical synthesis, 3D structure, and ASIC binding site of the toxin mambalgin-2.
AB  - Mambalgins are a novel class of snake venom components that exert potent
      analgesic effects mediated through the inhibition of acid-sensing ion channels
      (ASICs). The 57-residue polypeptide mambalgin-2 (Ma-2) was synthesized by using a
      combination of solid-phase peptide synthesis and native chemical ligation. The
      structure of the synthetic toxin, determined using homonuclear NMR, revealed an
      unusual three-finger toxin fold reminiscent of functionally unrelated snake
      toxins. Electrophysiological analysis of Ma-2 on wild-type and mutant ASIC1a
      receptors allowed us to identify alpha-helix 5, which borders on the functionally
      critical acidic pocket of the channel, as a major part of the Ma-2 binding site.
      This region is also crucial for the interaction of ASIC1a with the spider toxin
      PcTx1, thus suggesting that the binding sites for these toxins substantially
      overlap. This work lays the foundation for structure-activity relationship (SAR)
      studies and further development of this promising analgesic peptide. 

PMID- 24323788
TI  - Cancer stem cells maintain a hierarchy of differentiation by creating their
      niche.
AB  - The self-renewal and differentiation properties of cancer stem cells (CSCs) are
      regulated and maintained by the CSC niche. However, the mechanism of this
      maintenance, especially the maintenance contributed by differentiated cancer
      cells, remains to be fully elucidated. Recently, we have established a model of
      CSCs, miPS-LLCcm, from mouse induced pluripotent stem cells (miPSCs). In vitro
      cultured miPS-LLCcm cells were autonomously balanced with stem-like cells and
      differentiated cells including vascular endothelial cells. Under these
      conditions, the CSC properties appeared to be stable in the presence of the
      factor(s) secreted by the differentiated cells. The factor(s) activated Notch
      signaling and promoted self-renewal of CSCs. In addition, the secreted factor(s)
      appeared to regulate the differentiation lineage of CSCs. Our results indicate
      that the differentiated progenies of CSCs containing vascular endothelium play
      important roles for regulating the CSC's properties. Therefore, miPS-LLCcm cells
      create their own in vitro niche to maintain themselves in the hierarchy of
      differentiating CSCs. 

PMID- 24323789
TI  - Quick diagnosis units--an effective alternative to hospitalization for diagnostic
      workup: a systematic review.
AB  - INTRODUCTION: This era of healthcare reform emphasizes improving value of care.
      Inpatient admissions for diagnostic evaluation put economic pressure on an
      already strained healthcare system. We conducted a systematic review of
      effectiveness of quick diagnosis units (QDUs), an established outpatient model
      for early diagnostic workups in Europe. METHODS: We searched MEDLINE and Embase
      for studies that focused on implementation of quick/rapid diagnosis units, with
      relevant Medical Subject Headings terms and keywords. Of 2047 studies, we
      selected 13 for full-text screening and bibliography review. Of these, 5 studies
      included at least 2 primary outcomes of interest and were included in our review.
      These units functioned as outpatient clinics, staffed by internists, nurses, and
      clerical staff, with expedited scheduling of outpatient diagnostic tests. Our
      primary outcome measures were final diagnosis, the mean time to final diagnosis,
      inpatient bed-days saved per patient, and costs saved per patient. We also
      studied discharge disposition, care preferences, and safety data. RESULTS: About
      18% to 30% of patients were diagnosed with malignancy, with an average time to
      diagnosis of 6 to 11 days. Inpatient bed-days saved per patient ranged from 4.5
      to 7. Savings from fixed costs of hospitalization ranged from $2336(?1764) to
      $3304(?2514) for each patient enrolled in the protocol. The QDU model was
      preferred by 88% of patients, and patient satisfaction rates were 95% to 97%.
      CONCLUSIONS: QDUs seem an effective and cost-saving alternative to inpatient
      hospitalization, and appear to be a safe approach for diagnostic workup of
      potentially severe diseases in select patient populations, although there are
      limited safety data available.

PMID- 24323790
TI  - Egg- or cell culture-derived hemagglutinin mutations impair virus stability and
      antigen content of inactivated influenza vaccines.
AB  - Egg-derived viruses are the only available seed material for influenza vaccine
      production. Vaccine manufacturing is done in embryonated chicken eggs, MDCK or
      Vero cells. In order to contribute to efficient production of influenza vaccines,
      we investigate whether the quality of inactivated vaccines is influenced by the
      propagation substrate. We demonstrate that H3N2 egg-derived seed viruses
      (A/Brisbane/10/07, IVR147, and A/Uruguay/716/07) triggered the hemagglutinin (HA)
      conformational change under less acidic conditions (0.2-0.6 pH units) than
      antigenically similar primary isolates. This phenotype was associated with HA1
      (A138S, L194P) and HA2 (D160N) substitutions, and strongly related to decreased
      virus stability towards acidic pH and elevated temperature. The subsequent
      propagation of H3N2 and H1N1 egg-derived seed viruses in MDCK and Vero cells
      induced HA2 N50K (H1N1) and D160E (H3N2) mutations, improving virus growth in
      cell culture but further impairing virus stability. The prevention of the loss or
      recovery of stability was possible by cultivation at acidified conditions.
      Viruses carrying less stable HAs are more sensitive for HA conformational change
      during concentration, purification and storage. This results in decreased
      detectable HA antigen content - the main potency marker for inactivated influenza
      vaccines. Thus, virus stability can be a useful marker for predicting the
      manufacturing scope of seed viruses. 

PMID- 24323791
TI  - Reducing iodinated contrast volume by manipulating injection pressure during
      coronary angiography.
AB  - OBJECTIVE: To evaluate the impact of a device-mediated modification of the
      injection pressure profile on iodinated contrast volumes during coronary
      angiography and percutaneous coronary intervention (PCI). BACKGROUND: The
      development of iodinated contrast-induced acute kidney injury (AKI) is associated
      with significant morbidity and mortality in patients undergoing coronary
      angiography and intervention, particularly in the setting of ST-elevation
      myocardial infarction. Iodinated contrast volume is a recognized risk factor for
      iodinated contrast-induced AKI. Mitigation of iodinated contrast loss due to
      coronary iodinated contrast reflux represents a potential means to reduce
      iodinated contrast volume. METHOD AND RESULTS: We assessed the effectiveness of
      injection pressure modulation using an iodinated contrast conservation system
      (CCS), in 21 patients undergoing diagnostic coronary angiography or PCI. System
      activation was associated with a marked reduction in iodinated contrast injection
      compared with standard imaging (3.5 +/- 1.1 vs. 5.4 +/- 1.7 mL, P < 0.001).
      Paired images were obtained in 59 instances with significantly less iodinated
      contrast use with CCS use (3.3 +/- 1.1 vs. 5.5 +/- 1.6 mL, P < 0.001), with
      comparable image quality in 98% of cases. CONCLUSIONS: Modulation of iodinated
      contrast injection pressure provides a novel potential means to reduce iodinated
      contrast volumes by attenuating inefficient losses due to ostial reflux. Future
      studies are required to define the ability of the CCS to reduce total iodinated
      contrast volume and to impact upon the risk of iodinated contrast-induced AKI.

PMID- 24323792
TI  - Microsurgical anatomy of the trigeminal nerve.
AB  - The objective of this study is to review surgical anatomy of the trigeminal
      nerve. We also demonstrate some pictures involving the trigeminal nerve and its
      surrounding connective and neurovascular structures. Ten adult cadaveric heads
      were studied, using a magnification ranging from 3* to 40*, after perfusion of
      the arteries and veins with colored latex. The trigeminal nerve is the largest
      and most complex of the cranial nerves. It serves as a major conduit of sensory
      input from the face and provides motor innervation to the muscles of mastication.
      Because of its size and complexity, it is essential to have thorough knowledge of
      the nerve before diagnoses and treatment of the pathologic processes in the
      orofacial, temporomandibular, infratemporal, and pterygopalatine areas. The
      trigeminal nerve is encountered with imaging or surgery of the skull base
      surgery. Thus, a comprehensive knowledge of the anatomy of the trigeminal nerve
      is crucial for performing the surgical procedures without significant
      complication.

PMID- 24323794
TI  - Smoking cessation: benefits versus risks of using pharmacotherapy to quit.

PMID- 24323793
TI  - Cardiovascular events associated with smoking cessation pharmacotherapies: a
      network meta-analysis.
AB  - BACKGROUND: Stopping smoking is associated with many important improvements in
      health and quality of life. The use of cessation medications is recommended to
      increase the likelihood of quitting. However, there is historical and renewed
      concern that smoking cessation therapies may increase the risk of cardiovascular
      disease events associated within the quitting period. We aimed to examine whether
      the 3 licensed smoking cessation therapies-nicotine replacement therapy,
      bupropion, and varenicline-were associated with an increased risk of
      cardiovascular disease events using a network meta-analysis. METHODS AND RESULTS:
      We searched 10 electronic databases, were in communication with authors of
      published randomized, clinical trials (RCTs), and accessed internal US Food and
      Drug Administration reports. We included any RCT of the 3 treatments that
      reported cardiovascular disease outcomes. Among 63 eligible RCTs involving 21
      nicotine replacement therapy RCTs, 28 bupropion RCTs, and 18 varenicline RCTs, we
      found no increase in the risk of all cardiovascular disease events with bupropion
      (relative risk [RR], 0.98; 95% confidence interval [CI], 0.54-1.73) or
      varenicline (RR, 1.30; 95% CI, 0.79-2.23). There was an elevated risk associated
      with nicotine replacement therapy that was driven predominantly by less serious
      events (RR, 2.29; 95% CI, 1.39-3.82). When we examined major adverse
      cardiovascular events, we found a protective effect with bupropion (RR, 0.45; 95%
      CI, 0.21-0.85) and no clear evidence of harm with varenicline (RR, 1.34; 95% CI,
      0.66-2.66) or nicotine replacement therapy (RR, 1.95; 95% CI, 0.26-4.30).
      CONCLUSION: Smoking cessation therapies do not appear to raise the risk of
      serious cardiovascular disease events.

PMID- 24323795
TI  - Efficacy and safety of dabigatran compared with warfarin in relation to baseline
      renal function in patients with atrial fibrillation: a RE-LY (Randomized
      Evaluation of Long-term Anticoagulation Therapy) trial analysis.
AB  - BACKGROUND: Renal impairment increases the risk of stroke and bleeding in
      patients with atrial fibrillation. In the Randomized Evaluation of Long-Term
      Anticoagulant Therapy (RELY) trial, dabigatran, with ~80% renal elimination,
      displayed superiority over warfarin for prevention of stroke and systemic
      embolism in the 150-mg dose and significantly less major bleeding in the 110-mg
      dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified
      study investigated these outcomes in relation to renal function. METHODS AND
      RESULTS: Glomerular filtration rate was estimated with the Cockcroft-Gault,
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of
      Diet in Renal Disease (MDRD) equations in all randomized patients with available
      creatinine at baseline (n=17 951), and cystatin C-based glomerular filtration
      rate was estimated in a subpopulation with measurements available (n=6190). A
      glomerular filtration rate >=80, 50 to <80, and <50 mL/min was estimated in
      32.6%, 47.6%, and 19.8% and in 21.6%, 59.6%, and 18.8% of patients based on
      Cockcroft-Gault and CKD-EPI, respectively. Rates of stroke or systemic embolism,
      major bleeding, and all-cause mortality increased as renal function decreased.
      The rates of stroke or systemic embolism were lower with dabigatran 150 mg and
      similar with 110 mg twice daily compared with warfarin, without significant
      heterogeneity in subgroups defined by renal function (interaction P>0.1 for all).
      For the outcome of major bleeding, there were significant interactions between
      treatment and renal function according to CKD-EPI and MDRD equations,
      respectively (P<0.05). The relative reduction in major bleeding with either
      dabigatran dose compared with warfarin was greater in patients with glomerular
      filtration rate >=80 mL/min. CONCLUSIONS: The efficacy of both dosages of
      dabigatran was consistent with the overall trial irrespective of renal function.
      However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed
      significantly lower rates of major bleeding in patients with glomerular
      filtration rate >=80 mL/min. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

PMID- 24323797
TI  - CE analysis of single wood cells performing hydrolysis and preconcentration in
      open microchannels.
AB  - In the present work, monosaccharides from pulp samples and single wood fibers
      were analyzed with CE, using indirect detection due to the lack of chromophores
      on the monosaccharides. The hydrolysis degradation of cellulose and hemicellulose
      into monosaccharides was performed using TFA, either in bulk scale or in
      microscale. In the microscale, one single wood fiber was hydrolyzed in an open
      microchannel manufactured on a silicon microchip with the dimensions 50 MUm * 50
      MUm (length 1 or 3 cm). The low monosaccharide amounts derived from a single
      fiber implied that a preconcentration step was necessary to increase the
      detectability. Thus, an electromigration preconcentration of the hydrolyzed
      samples was performed within the microchannel, which resulted in a significantly
      enhanced signal intensity of the monosaccharides. In addition to the experimental
      study, computer simulations were performed regarding the preconcentration step of
      monosaccharides. The results from these simulations correlated well with the
      experimental results. 

PMID- 24323798
TI  - Experimental evaluations of head scatter factor calculation by use of a Gaussian
      function.
AB  - In external beam radiation therapy, it is important to calculate the output of
      the linear accelerator. The head scatter factor, S h, is one of the important
      factors for calculation of Monitor Unit, which changes with the size of the
      irradiation field. In irregular fields shaped by multileaf collimators (MLCs), it
      is difficult to calculate S h precisely. S h comprises backscatter from the upper
      and lower secondary collimators and scatter from the flattening filter. We
      measured the effect of backscatter on a monitor chamber (S b), and we modeled the
      scatter from a flattening filter using a Gaussian distribution. The modeled
      parameters used in this method are derived from measurements of square field
      sizes on the central axis. Furthermore, we divided an MLC irregular field in the
      shape of fans and integrated the scatter from a flattening filter by a method
      similar to Clarkson's sector integration. We were able to calculate S h with <1%
      error in comparison with measurements, even with a field setting with an error of
      >3% by the conventional method. This method requires no special measuring tools
      or software.

PMID- 24323796
TI  - Intravenous infusion of nerve growth factor-secreting monocytes supports the
      survival of cholinergic neurons in the nucleus basalis of Meynert in
      hypercholesterolemia Brown-Norway rats.
AB  - The recruitment of monocytes into the brain has been implicated in Alzheimer's
      disease and recent studies have indicated that monocytes can reduce amyloid
      plaque burden. Our previous investigations have shown that hypercholesterolemic
      rats develop cognitive, cholinergic, and blood-brain barrier dysfunction, but do
      not develop amyloid plaques. This study was designed to evaluate the effects of
      repeated intravenous (i.v.) infusion (via the dorsal penile vein) of primary
      monocytes on cognition, the cholinergic system, and cortical cytokine levels in
      hypercholesterolemia Brown-Norway rats. In addition, we also transduced the
      monocytes with nerve growth factor (NGF) to evaluate whether these cells could be
      used to deliver a neuroprotective agent to the brain. Our results indicate that
      repeated i.v. infused monocytes migrate into the brains of hypercholesterolemic
      rats; however, this migration does not translate into marked effects on learning.
      Animals receiving NGF-loaded monocytes demonstrate slightly improved learning and
      significantly elevated cholinergic neuron staining compared to treatment with
      monocytes alone. Furthermore, our data indicate that repeated infusion of
      monocytes does not lead to elevated cytokine secretion, indicating that no
      inflammatory response is induced. This study provides an experimental attempt to
      evaluate the effects of blood-derived primary monocytes in hypercholesterolemia
      rats.

PMID- 24323799
TI  - Medial meniscal displacement and strain in three dimensions under compressive
      loads: MR assessment.
AB  - PURPOSE: To investigate the 3D displacement and the local strain of the medial
      meniscus and its attachments under compressive loading. MATERIALS AND METHODS:
      Magnetic resonance imaging (MRI) scans of six porcine knee joints were performed
      under unloaded and loaded conditions (100% and 200% body weight [BW]). Volumes
      were registered to obtain a 3D displacement field of the medial meniscus and its
      attachments, which were divided into five anatomic compartments. Finally,
      displacements of the center of mass of each compartment and the local strain were
      analyzed. RESULTS: The meniscus and its attachments significantly displaced by up
      to 2.6 +/- 1.2 mm (P < 0.01) under knee joint loads of 200% BW. An increase of
      0.9 mm in the distance between posterior and anterior horn (P < 0.001) was
      observed. The meniscus and its attachment showed an average radial stretch of
      0.6%, an average circumferential stretch of 0.9%, and an average axial
      compression of 11.6% at 200% BW. CONCLUSION: High-resolution MRI was successfully
      combined with image registration to investigate the displacement and strain of
      the meniscus and its attachments under compression. The results of this study
      contribute to the basic understanding of meniscal movement which may impact the
      design of meniscal implants and the validation of finite element models in the
      future.

PMID- 24323800
TI  - A synthetic oligonucleotide model for evaluating the oxidation and crosslinking
      propensities of natural furan-modified DNA.
AB  - We have previously developed a crosslinking methodology for oligonucleotides
      based on the incorporation of furan moieties, which can be selectively oxidised
      to reactive intermediates that will quickly react with the opposite bases in DNA,
      forming toxic interstrand crosslinks (ICLs). Furan moieties also occur in natural
      DNA, as a result of oxidative stress. Moreover, the furan-containing degradation
      product of this modified DNA-kinetin-has been found to display beneficial anti
      ageing effects. To investigate the apparent discrepancy between the effects of
      the synthetic and the natural furan modifications in DNA, a quick and easy
      postsynthetic method providing access to the natural modification in short
      synthetic oligonucleotides was developed. On checking for potential crosslinking
      propensity, we found that the furan moiety does indeed undergo oxidation, in this
      way functioning as an important scavenger for oxidative stress. The reactive
      intermediate, however, was shown to degrade without producing toxic crosslinked
      products. 

PMID- 24323801
TI  - Use of a group concept mapping approach to define learning outcomes for an
      interdisciplinary module in medicine.
AB  - Learning outcomes are typically developed using standard group-based consensus
      methods. Two main constraints with standard techniques such as the Delphi method
      or expert working group processes are: (1) the ability to generate a
      comprehensive set of outcomes and (2) the capacity to reach agreement on them. We
      describe the first application of Group Concept Mapping (GCM) to the development
      of learning outcomes for an interdisciplinary module in medicine and engineering.
      The biomedical design module facilitates undergraduate participation in clinician
      mentored team-based projects that prepare students for a multidisciplinary work
      environment. GCM attempts to mitigate the weaknesses of other consensus methods
      by excluding pre-determined classification schemes and inter-coder discussion,
      and by requiring just one round of data structuring. Academic members from
      medicine and engineering schools at three EU higher education institutions
      participated in this study. Data analysis, which included multidimensional
      scaling and hierarchical cluster analysis, identified two main categories of
      outcomes: technical skills (new advancement in design process with special
      attention to users, commercialization and standardization) and transversal skills
      such as working effectively in teams and creative problem solving. The study
      emphasizes the need to address the highest order of learning taxonomy (analysis,
      synthesis, problem solving, creativity) when defining learning outcomes. 

PMID- 24323802
TI  - Hospital-wide survey of the adequacy in the number of vascular catheters and
      catheter lumens.
AB  - BACKGROUND: Removal of unnecessary catheters has been proposed as an important
      measure to reduce catheter-related morbidity. Nevertheless, there is scarce
      information about the potential magnitude of such intervention. OBJECTIVE: The
      present study was aimed at analyzing the appropriateness of use of vascular
      catheters and catheter lumens in the inpatient setting. DESIGN: Cross-sectional
      survey. SETTING: The entire population of adult inpatients admitted to a 1368-bed
      tertiary-care hospital in a single day. MEASUREMENTS: We used a set of
      preestablished criteria to evaluate the appropriateness of use of vascular
      catheters and catheter lumens according to the number and administration regimen
      of intravenous drugs. RESULTS: Out of 834 patients, 575 (68.9%) had >=1 vascular
      catheters in place on the day of the survey. The type and distribution of the 703
      surveyed catheters were peripheral venous catheter, 80.6%; central venous
      catheter, 15.8%; and arterial catheter, 3.6%. We found an overall mean of 2.06 +/
      0.82 lumens per catheter, with significant differences between intensive care
      units and conventional wards (P < 0.0001). Based on our criteria, 126 out of 575
      patients (21.9%) had an inappropriate number of catheters (medical wards, 20.0%;
      surgical wards, 23.9%; intensive care units, 26.3%), and 631 out of 14248
      nonarterial catheter lumens (43.6%) were considered unnecessary. CONCLUSIONS:
      Significant room exists for improving the adequacy of the number of vascular
      catheters and catheter lumens as a potentially useful tool for decreasing the
      incidence of catheter-related bloodstream infection.

PMID- 24323804
TI  - Peripheral immune response to CNS injury.

PMID- 24323803
TI  - The emerging technique of electromagnetic navigation bronchoscopy-guided fine
      needle aspiration of peripheral lung lesions: promising results in 50 lesions.
AB  - BACKGROUND: Literature on the diagnostic yield of electromagnetic navigation
      bronchoscopy (ENB) with ENB-guided fine-needle aspiration (ENB-FNA) in peripheral
      lung lesions (PLLs) that measure <= 2 cm is scarce. Data on the diagnostic yield
      of ENB-FNA for PLLs when performed in conjunction with positron emission
      tomography-computed tomography (PET-CT), rapid on-site evaluation (ROSE), ENB
      guided bronchial brushing (ENB-BB), and ENB-guided transbronchial biopsy (ENB
      TBx) is also limited. In this study, the authors evaluated their experience with
      ENB-FNA performed in conjunction with all 4 modalities: PET-CT, ROSE, ENB-BB, and
      ENB-TBx. METHODS: ENB-FNA and other tests over a 2-year-period (from July 2011 to
      July 2013) were retrospectively reviewed. RESULTS: There were 50 PLLs from 40
      patients, and the mean lesion size (available for 45 PLLs) was 2.6 cm: these
      included 24 PLLs that measured <= 2 cm and 21 PLLs that measured > 2.0 cm. The
      ENB-FNA diagnosis was malignant in 17 lesions, atypical in 1 lesion, benign in 31
      lesions, and nondiagnostic in 1 lesion. On the basis of lesion size, the
      diagnostic yield of PLLs was 87% in lesions <= 2 cm and 100% in lesions > 2.0 cm
      (P = 0.5; not significant). Follow-up available in 49 of 50 PLLs from 39 patients
      had an overall diagnostic yield of 94% for ENB-FNA. The diagnostic yield of PET
      CT (available in 31 of 50 PLLs) and of ENB-BB and ENB-TBx (available in 40 of 50
      PLLs) in conjunction with ENB-FNA was 61% and 95%, respectively. ROSE was
      performed in 46 of 50 PLLs: the overall sensitivity of ROSE and ENB-FNA was 85%
      and 89.4%, respectively, and their specificity was 96.5% and 100%, respectively.
      There were no procedure-related complications. CONCLUSIONS: The high overall
      diagnostic yield of 94% and fewer complications make ENB-FNA a useful modality
      for the assessment of PLLs. In this study, ROSE was useful, whereas PET-CT, ENB
      BB, and ENB-TBx were not useful in the evaluation of PLLs.

PMID- 24323805
TI  - Human in vitro models of ischaemic stroke: a test bed for translation.

PMID- 24323806
TI  - Autoimmune responses to brain following stroke.
AB  - This review provides a synthesis of the work done by our laboratory that
      demonstrates the presence of cellular immune responses directed towards brain
      antigens in animals following experimental stroke as well as in patients
      following ischemic stroke. These responses include both antigen-specific TH1(+)
      responses, which are associated with worse stroke outcome, and antigen-specific
      TREG responses, which are associated with better stroke outcome. The likelihood
      of developing a detrimental TH1(+) response to brain antigens is increased by
      administration of a systemic inflammatory stimulus in experimental stroke and by
      systemic infection in patients with stroke. We propose that the microenvironment
      within the lymph nodes and brain is altered by systemic inflammation and allows
      for bystander activation of lymphocytes and the development of autoimmune
      responses to brain antigens following cerebral ischemic injury. 

PMID- 24323807
TI  - Progenitor cells: therapeutic targets after traumatic brain injury.
AB  - Traumatic brain injuries and their associated treatments carry high cost in both
      financial impact and morbidity to human life. Recent studies and trials present
      promising results in reducing secondary injury in the days and weeks following
      the primary insult. A number of studies, both pre-clinical and clinical, have
      found that different populations of stem/progenitor cells result in a reduction
      of inflammation, maintenance of the blood brain barrier, and an overall improved
      prognosis. The mechanism of action of these cellular therapies appears to rely
      upon the ability of the cells to influence microglia/macrophage phenotype and
      alter the state of the inflammatory response. The spleen has become an area of
      intense interest as an arena where therapeutic cells interact with reactive
      macrophages to cause system-level changes in immune activity. Additionally, the
      spleen enacts anti-inflammatory responses originating in the CNS, delivered
      through vagal activity with a recently described mechanism culminating in
      acetylcholine release. This review provides a summary of recent findings as to
      the mechanisms of action observed in current cellular therapies. 

PMID- 24323809
TI  - Bone marrow chimeras in the study of experimental stroke.
AB  - Inflammation is known to contribute to stroke evolution, and poststroke immune
      responses have been documented to emanate from the brain via microglia. However,
      circulating immune cells are increasingly recognized to play a significant role
      as well. Recent work has demonstrated the importance of the peripheral
      circulation and stroke pathogenesis. Understanding how the peripheral circulation
      contributes to ischemic brain injury may reveal important therapeutic targets and
      strategies. The use of bone marrow chimeras can be a useful tool in understanding
      the relative contributions of brain resident and peripheral inflammatory
      responses. 

PMID- 24323808
TI  - Immunological aspects in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by progressive motor neuron death, leading to muscle atrophy, paralysis, and
      death usually within 3 to 5 years after diagnosis. Most cases are sporadic, with
      still undefined etiopathogenesis. Both the innate and adaptive immune systems are
      involved in ALS, with special participation of T lymphocytes and microglia.
      Inflammation plays a dual role in the disease, protective and T regulatory cell
      rich in the early stages and deleterious as disease progresses. Attempts to
      modulate immune/inflammatory system response are reported in the literature, and
      while beneficial effects are achieved in ALS animal models, results of most
      clinical trials have been disappointing. The impaired blood-brain barrier is an
      important feature in the pathogenesis of ALS and likely affects the immune system
      response. The present review describes the role of the immune system in ALS
      pathogenesis and the tight coupling of immunity and central nervous system
      barrier function. 

PMID- 24323810
TI  - Unique effects of compounds active at both cannabinoid and serotonin receptors
      during stroke.
AB  - We reported previously that both a cannabinoid receptor 2 (CB2R) agonist and a
      cannabinoid receptor 1 (CB1R) antagonist were protective in the treatment of
      transient middle cerebral artery occlusion/reperfusion injury (MCAO/R) and that
      they acted in a synergistic manner when administered in combination. The goal of
      the current study was to determine which of the potential cannabinoid receptors
      participate in the protective effects of this drug combination in a mouse model
      of MCAO/R. The effects of administration of the CB2R agonist/CB1R antagonist
      combination on infarct size and cerebral blood flow during a 1-h occlusion were
      tested in CB1R-deficient animals, CB2R-deficient animals, and animals treated
      with capsazepine, the antagonist for the vanilloid receptor type I (TRPV1) and
      WAY100135, the antagonist for the hydroxytryptamine1A receptor (5-HT1A). The
      protective effect of the CB2R agonist/CB1R antagonist combination on infarct size
      was not influenced by the absence of the CB1R nor by blocking the TRPV1 receptor,
      but was attenuated by the absence of CB2R and by blocking the 5-HT1A receptor.
      Increases in cerebral blood flow and arteriolar diameter were also found to be
      independent of the CB1R and TRPV1 receptor. In conclusion, administration of the
      CB2R agonist/CB1R antagonist combination causes a significant reduction in
      infarct size in the MCAO/R model. The protective effect involves both the CB2R
      and the 5-HT1A receptor. Neither the CB1R nor the TRPV1 receptors appear to
      participate in this response. 

PMID- 24323811
TI  - CCL20 Is Associated with Neurodegeneration Following Experimental Traumatic Brain
      Injury and Promotes Cellular Toxicity In Vitro.
AB  - Traumatic brain injury (TBI) is complex and involves multiple processes that
      contribute to functional decline. Progressive neuropathies result from delayed
      cellular death following the initial impact. Although the precise mechanisms
      responsible for delayed injury are unknown, numerous data implicate a role for
      the peripheral immune system in perpetuating neuroinflammation after TBI. A
      previous report demonstrated that splenic CCL20 chemokine expression was
      upregulated 24 h after lateral fluid percussive impact (LFPI), prior to neuronal
      expression but consistent with neurodegeneration. Here, we expand on those data
      to report increased CCL20 protein expression in white matter 48 h after LFPI and
      demonstrate that CCL20 is directly toxic to primary neurons and oligodendrocytes
      subjected to oxygen glucose deprivation. The temporal expression profile of
      CCL20, coupled with in vitro toxicity to primary cells, suggests that this
      chemokine exerts deleterious effects on cell viability following TBI. These
      findings warrant further investigations into the use of CCL20 as a potential
      biomarker and/or therapeutic target. 

PMID- 24323812
TI  - CT Density Changes with Rapid Onset Acute, Severe, Focal Cerebral Ischemia in
      Monkeys.
AB  - Computerized tomography (CT) is the most often used imaging modality in the
      evaluation of acute clinical stroke. However, the rapidity with which CT density
      changes occur after acute, severe, focal ischemia cannot be determined
      clinically. Even if the time of symptom onset is known, clinical stroke severity
      is highly variable. We studied the time course of CT density change after severe,
      rapid onset, acute, focal ischemia as documented by stable xenon CT cerebral
      blood flow (CBF) in monkeys. Eight monkeys (Macaca mulatta) were subjected to
      transorbital occlusion of the left posterior cerebral, anterior, middle, and
      internal carotid arteries to induce focal ischemia. CT density Hounsfield units
      (HU), CBF by stable xenon CT, arterial blood pressure, and blood gases were
      measured before occlusion, immediately after occlusion, at 30 min, and hourly for
      up to 6 h. Occlusion of the cerebral arteries decreased CBF to 8 +/- 5 ml/100 g/
      min within 15 min postocclusion. At 6 h, CBF was unchanged at 9 +/- 4 ml/100 g/
      min. CT density within the ischemic core fell from 42 to 38 HU immediately after
      occlusion (P < 0.05), rose transiently, then fell at 2 h (P < 0.01) and plateaued
      at 36 +/- 5 HU for a total decrease of 4-5 HU between 4 and 6 h poststroke.
      Changes in CT density lag severe focal ischemia by 2 h. Thus, when CT hypodensity
      is seen in acute stroke, it is likely 2 h old. It also provides an explanation
      for the phenomenon of clinical CT mismatch with clinical deficits and normal CT. 

PMID- 24323813
TI  - Physiologic Effects of Xenon in Xenon-CT Cerebral Blood Flow Studies on Comatose
      Patients.
AB  - Despite more than 30 years of clinical use, questions remain about the safety of
      xenon gas in Xenon-CT cerebral blood flow (XeCTCBF) studies. In particular,
      xenon's effect on brain oxygen (PbtO2) in comatose patients is not well defined.
      Our objective was to assess the effect of a 4.5-min inhalation of 28 % stable
      xenon on several physiologic variables, including intracranial pressure (ICP),
      cerebral perfusion pressure (CPP), and PbtO2 in comatose patients (Glasgow Coma
      Scale [GCS] <= 8). Thirty-seven comatose patients who underwent 73 XeCTCBF
      studies were identified retrospectively from a prospective observational
      database. Changes in MAP, HR, SaO2, EtCO2, ICP, CPP, and PbtO2 measured at the
      start of xenon administration and every minute for 5 min thereafter were
      assessed. The maximum change in each variable also was determined for each scan
      to tabulate clinically relevant changes. Statistically, but not clinically
      significant changes in MAP, HR, and EtCO2 were seen. Xenon had no effect on ICP,
      and a small, but clinically insignificant decrease in CPP and PbtO2, was
      observed. There was a varied response to xenon in most measured variables.
      Clinically significant changes in each were infrequent, and readily reversed with
      the cessation of the gas. We conclude that xenon does not appear to have a
      clinically significant effect on ICP, CPP, and PbtO2 and so appears safe to
      evaluate cerebral blood flow in comatose patients. 

PMID- 24323814
TI  - Comment on: "Tumor aggressiveness and patient outcome in cancer of the pancreas
      assessed by dynamic 18F-FDG PET/CT".

PMID- 24323815
TI  - Reply: Comment on: "Tumor aggressiveness and patient outcome in cancer of the
      pancreas assessed by dynamic 18F-FDG PET/CT".

PMID- 24323816
TI  - Understanding SUV variability in reference tissue for 18F-FDG PET with a simple
      measurement model.

PMID- 24323818
TI  - A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a
      pathogenic mitochondrial DNA mutation for Leber's hereditary optic neuropathy:
      clinical commentary.

PMID- 24323817
TI  - Characterization of neuromyelitis optica and neuromyelitis optica spectrum
      disorder patients with a late onset.
AB  - BACKGROUND: Few data are available for patients with a late onset (>= 50 years)
      of neuromyelitis optica (LONMO) or neuromyelitis optica spectrum disease
      (LONMOSD), defined by an optic neuritis/longitudinally extensive transverse
      myelitis with aquaporin-4 antibodies (AQP4-Ab). OBJECTIVE: To characterize LONMO
      and LONMOSD, and to analyze their predictive factors of disability and death.
      METHODS: We identified 430 patients from four cohorts of NMO/NMOSD in France,
      Germany, Turkey and UK. We extracted the late onset patients and analyzed them
      for predictive factors of disability and death, using the Cox proportional model.
      RESULTS: We followed up on 63 patients with LONMO and 45 with LONMOSD during a
      mean of 4.6 years. This LONMO/LONMOSD cohort was mainly of Caucasian origin
      (93%), women (80%), seropositive for AQP4-Ab (85%) and from 50 to 82.5 years of
      age at onset. No progressive course was noted. At last follow-up, the median
      Expanded Disability Status Scale (EDSS) scores were 5.5 and 6 in the LONMO and
      LONMOSD groups, respectively. Outcome was mainly characterized by motor
      disability and relatively good visual function. At last follow-up, 14 patients
      had died, including seven (50%) due to acute myelitis and six (43%) because of
      opportunistic infections. The EDSS 4 score was independently predicted by an
      older age at onset, as a continuous variable after 50 years of age. Death was
      predicted by two independent factors: an older age at onset and a high annualized
      relapse rate. CONCLUSION: LONMO/LONMOSD is particularly severe, with a high rate
      of motor impairment and death.

PMID- 24323819
TI  - Cerebrospinal fluid pleocytosis in multiple sclerosis patients with lesions
      showing reduced diffusion.
AB  - In multiple sclerosis (MS) occasionally acute lesions show a reduced apparent
      diffusion coefficient (ADC) on magnetic resonance imaging (MRI); however, the
      underlying mechanism of this phenomenon is not known. We compared cerebrospinal
      fluid (CSF) findings with diffusion MRI signal characteristics of acute lesions
      in 25 patients with MS or a clinically isolated syndrome (CIS) later confirmed as
      MS. In nine of 25 patients investigated between days 1 and 4 after symptom onset,
      a reduced intralesional ADC value (-15% to -51%) was accompanied by a marked CSF
      pleocytosis (11-46 leukocytes/ul). Our results suggest that ADC reduction in
      acute MS lesions is a phenomenon that is possibly related to an aggressive
      inflammatory milieu as indirectly indicated by CSF pleocytosis. Furthermore, the
      ADC reduction and CSF pleocytosis were observed only early after symptom onset,
      which suggests that both are typically early and transient phenomena.

PMID- 24323820
TI  - Transcatheter closure of large patent ductus arteriosus using custom made
      devices.
AB  - There has been a paradigm shift in the transcatheter closure of patent ductus
      arteriosus (PDA) over the last 45 years. With the availability of various coils,
      plugs and occluders, PDA of almost all shapes and sizes are amenable to
      transcatheter closure. However, very large PDA diagnosed late in life are being
      referred for surgical closure in the absence of availability of large size
      devices, especially in developing countries. In this case series, we have
      described four patients with large PDA, three of which were closed by
      transcatheter custom made PDA occluders. (c) 2014 Wiley Periodicals, Inc.

PMID- 24323823
TI  - The naming of the cranial nerves: a historical review.
AB  - The giants of medicine and anatomy have each left their mark on the history of
      the cranial nerves, and much of the history of anatomic study can be viewed
      through the lens of how the cranial nerves were identified and named. A
      comprehensive literature review on the classification of the cranial names was
      performed. The identification of the cranial nerves began with Galen in the 2nd
      century AD and evolved up through the mid-20th century. In 1778, Samuel
      Sommerring, a German anatomist, classified the 12 cranial nerves as we recognize
      them today. This review expands on the excellent investigations of Flamm, Shaw,
      and Simon et al., with discussion of the historical identification as well as the
      process of naming the human cranial nerves.

PMID- 24323821
TI  - Associations of reproductive time events and intervals with breast cancer risk: a
      report from the Shanghai Breast Cancer Study.
AB  - While there is clear evidence for an association between later age at first live
      birth and increased breast cancer risk, associations with the timing of other
      reproductive events are less clear. As breast tissues undergo major structural
      and cellular changes during pregnancy, we examined associations between
      reproductive time events and intervals with breast cancer risk among parous women
      from the population-based Shanghai Breast Cancer Study (SBCS). Unconditional
      logistic regression was used to evaluate associations with breast cancer risk for
      3,269 cases and 3,341 controls. In addition to later age at first live birth,
      later ages at first pregnancy and last pregnancy were significantly associated
      with increased breast cancer risk (p-trend = 0.002, 0.015, 0.008, respectively);
      longer intervals from menarche to first or last live birth were also associated
      with increased risk (p-trend < 0.001, =0.018, respectively). Analyses stratified
      by menopausal status and estrogen receptor (ER)/progesterone receptor (PR) status
      revealed that associations for later age at first pregnancy or live birth and
      longer intervals from menarche to first or last live birth occurred among
      premenopausal women and ER+/PR+ breast cancers, whereas the association for later
      age at last pregnancy occurred among postmenopausal women and women with ER+/PR-
      or ER-/PR+ breast cancers. Because of the high correlation with other
      reproductive variables, models did not include adjustment for age at first live
      birth; when included, the significance of all associations was attenuated. These
      findings suggest that while reproductive time events and intervals play an
      important role in breast cancer etiology, contributions may differ by menopausal
      status and hormone receptor status of breast cancers. 

PMID- 24323824
TI  - Influence of process parameters on tablet bed microenvironmental factors during
      pan coating.
AB  - Recent studies have shown the importance of monitoring microenvironmental
      conditions (temperature, relative humidity) experienced by the tablet bed during
      a pan coating process, thereby necessitating the need to understand how various
      process parameters influence these microenvironmental conditions. The process
      parameters studied in this work include exhaust air temperature, spray rate,
      inlet airflow rate, gun-to-bed distance, coating suspension percent solids, and
      atomization and pattern air pressure. Each of these process parameters was found
      to have an impact on the tablet bed relative humidity (RH), as measured using
      PyroButton data logging devices. A higher tablet bed RH was obtained with an
      increase in spray rate and atomization air pressure and with a decrease in
      exhaust air temperature, inlet airflow rate, gun-to-bed distance, suspension
      percent solids, and pattern air pressure. Based on this work, it can be concluded
      that the tablet bed thermodynamic conditions are a cumulative effect of the
      various process conditions. A strong correlation between the tablet bed RH and
      the frequency of tablet coating defect (logo bridging) was established, with
      increasing RH resulting in a higher percent of logo bridging events. 

PMID- 24323825
TI  - Immunosuppressive drug therapy for preventing rejection following lung
      transplantation in cystic fibrosis.
AB  - BACKGROUND: For patients with cystic fibrosis and advanced pulmonary damage, lung
      transplantation is an available and viable option. However, graft rejection is an
      important potential consequence after lung transplantation. Immunosuppressive
      therapy is needed to prevent episodes of graft rejection and thus subsequently
      reduce morbidity and mortality in this population. There are a number of classes
      of immunosuppressive drugs which act on different components of the immune
      system. There is considerable variability in the use of immunosuppressive agents
      after lung transplantation in cystic fibrosis. While much of the research in
      immunosuppressive drug therapy has focused on the general population of lung
      transplant recipients, little is known about the comparative effectiveness and
      safety of these agents in patients with cystic fibrosis. OBJECTIVES: To assess
      the effects of individual drugs or combinations of drugs compared to placebo or
      other individual drugs or combinations of drugs in preventing rejection following
      lung transplantation in patients with cystic fibrosis. SEARCH METHODS: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register
      and scanned references of the potentially eligible study. We also searched the
      www.clinicaltrials.gov trials registry to obtain information on unpublished and
      ongoing studies.Date of latest search: 22 August 2013. SELECTION CRITERIA:
      Randomised and quasi-randomised studies. DATA COLLECTION AND ANALYSIS: We
      independently assessed the studies identified from our searches for inclusion in
      the review. Should eligible studies be identified and included in future updates
      of the review, we will independently extract data and assess the risk of bias.
      MAIN RESULTS: While two studies met our inclusion criteria, we did not include
      them in the review because the investigators of the studies did not report any
      information specific to patients with cystic fibrosis. Our attempts to obtain
      this information have not yet been successful. We will include any provided data
      in future updates of the review. AUTHORS' CONCLUSIONS: The lack of currently
      available evidence makes it impossible to make conclusions about the comparative
      efficacy and safety of the various immunosuppressive drugs among patients with
      cystic fibrosis after lung transplantation. A recent Cochrane review comparing
      tacrolimus with cyclosporine in all patients with lung transplantation (not
      restricted to patients with cystic fibrosis) reported no significant difference
      in mortality and risk of acute rejection. However, tacrolimus use was associated
      with lower risk of broncholitis obliterans syndrome and arterial hypertension and
      higher risk of diabetes mellitus. It should be noted that this review contained
      only a small number of included studies (n = 3) with a high risk of bias.
      Additional randomised studies are required to provide evidence for the benefit
      and safety of the use of immunosuppressive therapy among patients with cystic
      fibrosis after lung transplantation.

PMID- 24323826
TI  - Powder, paper and foam of few-layer graphene prepared in high yield by
      electrochemical intercalation exfoliation of expanded graphite.
AB  - A facile and high-yield approach to the preparation of few-layer graphene (FLG)
      by electrochemical intercalation exfoliation (EIE) of expanded graphite in
      sulfuric acid electrolyte is reported. Stage-1 H2SO4-graphite intercalation
      compound is used as a key intermediate in EIE to realize the efficient
      exfoliation. The yield of the FLG sheets (<7 layers) with large lateral sizes
      (tens of microns) is more than 75% relative to the total amount of starting
      expanded graphite. A low degree of oxygen functionalization existing in the
      prepared FLG flakes enables them to disperse effectively, which contributes to
      the film-forming characteristics of the FLG flakes. These electrochemically
      exfoliated FLG flakes are integrated into several kinds of macroscopic graphene
      structures. Flexible and freestanding graphene papers made of the FLG flakes
      retain excellent conductivity (~24,500 S m(-1)). Three-dimensional (3D) graphene
      foams with light weight are fabricated from the FLG flakes by the use of Ni foams
      as self-sacrifice templates. Furthermore, 3D graphene/Ni foams without any
      binders, which are used as supercapacitor electrodes in aqueous electrolyte,
      provide the specific capacitance of 113.2 F g(-1) at a current density of 0.5 A
      g(-1), retaining 90% capacitance after 1000 cycles.

PMID- 24323827
TI  - Recombination analysis of autosomal short tandem repeats in Chinese Han families.
AB  - Recombination fractions between forensic STRs can be extrapolated from the
      International HapMap Project, but the concordance between recombination fractions
      predicated from genetic maps and derived from observation of STR transmissions in
      families is still ambiguous for autosomal STRs because of limited family studies.
      Therefore, the main goal of this study is to compare recombination fractions
      estimated by pedigree analysis with those derived from HapMap phase SNP data.
      Genotypes of nine autosomal STR pairs (TPOX-D2S1772, D5S818-CSF1PO, D7S3048
      D7S820, D8S1132-D8S1179, TH01-D11S2368, vWA-D12S391, D13S325-D13S317, D18S51
      D18S1364, and D21S11-PentaD) from 207 two-generation families with two to five
      children (the number of families with five, four, three, and two children was 2,
      3, 20, and 182, respectively) were used to analyze the recombination. The linkage
      analysis showed that significant linkage was observed at six STR pairs (D5S818
      CSF1PO, D8S1132-D8S1179, TH01-D11S2368, vWA-D12S391, D13S325-D13S317, and D18S51
      D18S1364) with genetic distances <36.22 cM in HapMap. Their recombination
      fractions calculated from family data were very close to those derived from
      HapMap. However, three STR pairs of TPOX-D2S1772, D7S3048-D7S820, and D21S11
      PentaD showed no significant linkage with genetic distances from 43.38 to 91.49
      cM. Our results indicate that recombination fractions extrapolated from HapMap
      can provide a substitute if empirical data are unavailable for the linkage STR
      pair with a genetic distance spanned <36.22 cM. 

PMID- 24323829
TI  - Communication about existential issues with patients close to death--nurses'
      reflections on content, process and meaning.
AB  - OBJECTIVE: Encountering dying patients with implicit existential questions
      requires the nurses to have positive and comfortable attitude to talking about
      existential issues. This paper describes the nurses' reflections on existential
      issues in their communication with patients close to death. METHODS: Nurses (n =
      98) were recruited from a hospital, hospices and homecare teams. Each nurse
      participated in five group reflection sessions that were recorded, transcribed
      and analysed using qualitative content analysis. RESULTS: Three domains and nine
      themes emerged. The content domain of the existential conversation covered
      living, dying and relationships. The process domain dealt with using conversation
      techniques to open up conversations, being present and confirming. The third
      domain was about the meaning of existential conversation for nurses. The group
      reflections revealed a distinct awareness of the value of sensitivity and
      supportive conversations. CONCLUSION: This study supports the assertion that
      experience of talking about existential issues and supporting environment make
      nurses comfortable when counselling patients close to death. It was obvious from
      this study that having the courage to be present and confirming, having time and
      not trying to 'solve' every existential problem were the most important factors
      in conversations with the patients close to death.

PMID- 24323830
TI  - Clinical trials for neuroprotective therapies in intracerebral hemorrhage: a new
      roadmap from bench to bedside.
AB  - The most deadly form of stroke, intracerebral hemorrhage (ICH) continues to
      puzzle researchers and produce substantial decrements in the quality of patients'
      lives. Intensive basic research has devised many agents with putative benefit in
      mitigating the devastating effects of ICH, but these therapies have been largely
      ineffective in the transition to clinical trials. However, a steady translational
      pipeline continues to provide new avenues of treatment that may be effective in
      the management of this condition. In this review, we aim to summarize the array
      of neuroprotective clinical trials and techniques used in the history of ICH, and
      delineate the progression of relevant research to date. Furthermore, we provide
      insight into methods that may allow for better translation of basic science
      advances into productive clinical trials. 

PMID- 24323831
TI  - Elevated blood pressure causes larger hematoma in a rat model of intracerebral
      hemorrhage.
AB  - Hypertension has been recognized as an independent risk factor for intracerebral
      hemorrhage (ICH). The objective of this study was to assess the effect of
      chronically elevated blood pressure on amount of hematoma in a rat model of ICH.
      A total of 46 rats were divided into two groups-normotensive group (n = 18) and
      spontaneously hypertensive group (n = 28). To induce ICH, we delivered 2 MUL of
      collagenase solution (0.1 U/1 MUL normal saline) into the striatum. Each animal's
      brain was removed 24 h post-surgery for spectrophotometric hemoglobin assay.
      Equal or unequal variance t tests were performed to assess changes in variables
      between the hypertensive and normotensive groups. Tissue analysis revealed a
      statistically significant difference in optical density percent change at 540-nm
      wavelength for the hypertensive vs. the normotensive group (261.47 +/- 103.68 and
      133.33 +/- 58.53, p < 0.0001, respectively). As compared to the normotensive
      rats, hypertensive rats exhibited a higher neurological deficit, loss of balance
      and coordination, and loss of motor function. Our results demonstrated that
      hypertensive rats had significantly higher amounts of hemorrhage in comparison to
      normotensive ones. These findings support the need for further adequately powered
      studies to investigate differences in amount of hematoma and corresponding
      functional impairments due to ICH among hypertensive vs. normotensive rats. 

PMID- 24323832
TI  - Anti-inflammatory effect of amlodipine plus atorvastatin treatment on carotid
      atherosclerosis in zucker metabolic syndrome rats.
AB  - To investigate the effects of amlodipine in combination with atorvastatin on
      carotid atherosclerotic changes in metabolic syndrome, 8-week-old Zucker fatty
      rats were treated with vehicle, amlodipine, atorvastatin, or amlodipine in
      combination with atorvastatin for 28 days. Histological studies of common carotid
      arteries showed that lipid deposition determined by Sudan III staining was
      significantly reduced in rats treated with amlodipine or atorvastatin alone and
      was further reduced by amlodipine in combination with atorvastatin.
      Immunohistochemical studies of the pro-inflammatory cytokine tumor necrosis
      factor (TNF)-alpha, the arterial calcification initiator bone morphogenetic
      protein (BMP) 2, the angiogenic factor Notch1, and the smooth muscle cell marker
      alpha-smooth muscle actin (SMA) showed that the high expression of all four
      protein in vehicle-treated rats was greatly decreased by amlodipine,
      atorvastatin, or amlodipine in combination with atorvastatin, in ascending order.
      Double immunostaining showed marked colocalization of TNF-alpha with bone
      morphogenetic protein 2 and Notch1 with alpha-SMA in the vehicle group, which was
      greatly reduced by amlodipine plus atorvastatin. These data suggest that
      combination therapy may be more effective in preventing atherosclerotic processes
      and subsequent carotid vascular events than administrating amlodipine or
      atorvastatin alone in metabolic syndrome. 

PMID- 24323833
TI  - Prevention of hyperglycemic signal pathways in metabolic syndrome carotid artery
      of rats.
AB  - Obesity is the major risk factor for metabolic syndrome and atherosclerotic
      cardiocerebrovascular diseases and induces insulin resistance characterized by a
      dysfunction of insulin to activate insulin receptor /insulin receptor substrate
      1(IRS-1)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Zucker fatty rats (8
      weeks) were treated with vehicle (0.5 % methyl cellulose in physiological saline,
      p.o.), amlodipine (3 mg/kg/day, p.o.), atorvastatin (10 mg/kg/day, p.o.), or the
      combination of amlodipine plus atorvastatin (3 + 10 mg/kg/day, p.o.) for 28 days,
      and anti-insulin-like growth factor 1 (IGF-1)/IRS-1/PI3K/Akt pathways were
      evaluated. Our present immunohistochemical study first demonstrated that a
      combination of amlodipine plus atorvastatin treatment prevented an
      arteriosclerotic process compared to the single treatment with amlodipine or
      atorvastatin with strong recoveries of pTyr IRS-1, pPI3K, and pAkt expressions
      and with remarkable restraints of IGF-1 and pSer IRS-1. As a result, combination
      therapy with amlodipine plus atorvastatin showed a strong synergistic effect to
      prevent atherosclerotic processes. The present study newly suggests a synergistic
      benefit of combination therapy with amlodipine plus atorvastatin for strong
      prevention of atherosclerotic processes, which could reduce the clinical risk of
      cerebrovascular events for obesity patients. 

PMID- 24323834
TI  - Hyperglycemia accentuates persistent "functional uncoupling" of cerebral
      microvascular nitric oxide and superoxide following focal ischemia/reperfusion in
      rats.
AB  - Hyperglycemia worsens outcome in stroke patients and in a variety of stroke
      models, most prominently following prolonged ischemia and reperfusion. Vascular
      dysfunction has been associated with this worsened outcome, manifested by reduced
      reperfusion cerebral blood flow (CBF), as well as increased hemorrhagic
      transformation, edema, and mortality. The phenomenon of "uncoupling" of
      endothelial nitric oxide synthase (eNOS) has been associated with hyperglycemia
      in the periphery and results in a dysfunctional eNOS-generating superoxide
      radical ([Formula: see text]) in lieu of nitric oxide (NO). A net result of NOS
      uncoupling is reduction in blood flow and generation of a pro-thrombotic,
      inflammatory vascular phenotype that could explain many of the features of
      hyperglycemic stroke. Because the sources of increased [Formula: see text] and
      mechanisms of reduced NO are difficult to identify under in vivo pathological
      conditions, we have termed the presence of perivascular excess of [Formula: see
      text] expression relative to NO as "functional uncoupling." We hypothesized that
      hyperglycemia would induce a state of functional uncoupling in the cerebral
      microvasculature that would be exacerbated by transient focal ischemia. We
      examined the relative expression of systemically injected radical sensitive dyes
      in cerebral microvessel profiles in the basal and 24 h post-stroke brain in a rat
      model of middle cerebral artery occlusion and recanalization (MCAO/R) in controls
      and after hyperglycemia. We focused on the peri-infarct region because of its
      importance in penumbra extension and edema. Differential expression of
      fluorescent dyes sensitive to [Formula: see text] and NO in microvessel profiles
      were assessed in the peri-infarct region. Hyperglycemia was induced by
      streptozotocin 48 h prior to MCAO/R. We found that hyperglycemia resulted in an
      increase in [Formula: see text] relative to NO, a pattern consistent with
      functional uncoupling. This ratio was accentuated 24 h after MCA/O in both
      groups. Hyperglycemic rats showed a synergistic increase in the [Formula: see
      text]/NO ratio as well as reduced acute reperfusion CBF, increased infarct size,
      and enhanced expression of nitrotyrosine. While effects of hyperglycemia on
      oxidative radicals is well known, we showed for the first time that hyperglycemia
      synergistically worsened functional uncoupling in the peri-infarct
      microvasculature and that it persisted for the 24-h duration of the experiment.
      Persistent generation of microvascular [Formula: see text] and reduction in NO
      expression suggest potential late therapeutic targets to restore microvessel
      function and improve vascular outcomes in hyperglycemic stroke. 

PMID- 24323835
TI  - MRI blood-brain barrier permeability measurements to predict hemorrhagic
      transformation in a rat model of ischemic stroke.
AB  - Permeability imaging might add valuable information in the risk assessment of
      hemorrhagic transformation. This study evaluates the predictive value of blood
      brain barrier permeability (BBBP) measurements extracted from dynamic contrast
      enhanced MRI for hemorrhagic transformation in ischemic stroke. Spontaneously
      hypertensive and Wistar rats with 2 h filament occlusion of the right MCA
      underwent MRI during occlusion, at 4 and 24 h post reperfusion. BBBP was imaged
      by DCE imaging and quantified by Patlak analysis. Cresyl-violet staining was used
      to characterize hemorrhage in sacrificed rats at 24 h, immediately following the
      last imaging study. BBBP changes were evaluated at baseline, 4 and 24 h after
      reperfusion. Receiver-operating characteristic (ROC) analysis was performed to
      determine the most accurate BBBP threshold to predict hemorrhagic transformation.
      In animals showing macroscopic hemorrhage at 24 h, 95th BBBP percentile values
      ipsilateral were 0.323 [0.260, 0.387], 0.685 [0.385, 0.985], and 0.412 [0.210,
      0.613] ml/min.100 g (marginal mean [95%CI]) during occlusion, at 4 and 24 h post
      reperfusion, respectively. The BBBP values on the infarcted and contralateral
      side were significantly different at 4 (p = 0.034) and 24 h post reperfusion (p =
      0.031). The predictive value of BBBP in terms of macroscopic hemorrhage was
      highest 4 h after reperfusion (ROC area under the curve = 84 %) with a high
      negative predictive value (98.3 %) and limited positive predictive value (14.9 %)
      for a threshold of 0.35 ml/min.100g. Altered BBBP is a necessary but not
      sufficient condition to cause hemorrhagic transformation in rats with an infarct.
      Further research is needed to identify those additional risk factors that are
      required for hemorrhagic transformation to develop in the setting of ischemic
      stroke. 

PMID- 24323836
TI  - Structure-dependent binding of arylimidamides to the DNA minor groove.
AB  - Heterocyclic diamidines are strong DNA minor-groove binders and have excellent
      antiparasitic activity. To extend the biological activity of these compounds, a
      series of arylimidamides (AIAs) analogues, which have better uptake properties in
      Leishmania and Trypanosoma cruizi than diamidines, was prepared. The binding of
      the AIAs to DNA was investigated by Tm , fluorescence displacement titration,
      circular dichroism, DNase I footprinting, biosensor surface plasmon resonance, X
      ray crystallography and molecular modeling. These compounds form 1:1 complexes
      with AT sequences in the DNA minor groove, and the binding strength varies with
      substituent size, charge and polarity. These substituent-dependent structure and
      properties provide a SAR that can be used to estimate K values for binding to DNA
      in this series. The structural results and molecular modeling studies provide an
      explanation for the differences in binding affinities for AIAs. 

PMID- 24323837
TI  - Biodegradable herbicide delivery systems with slow diffusion in soil and UV
      protection properties.
AB  - BACKGROUND: New herbicidal formulations were designed by combining wheat gluten
      (WG), two montmorillonites (MMTs) (unmodified and organically modified) and a
      model pesticide (ethofumesate), and their performances were assessed through an
      integrative study conducted in soil using an experimental methodology with data
      modelling. RESULTS: All the WG formulations tested were effective in decreasing
      the apparent diffusivity of ethofumesate in soil in comparison with the non
      formulated active substance. The slow-release effect was significantly more
      pronounced in the presence of the organically modified MMT, confirming the
      importance of sorption mechanisms to reduce ethofumesate diffusion. The bioassays
      undertaken on watercress to evaluate herbicidal antigerminating performances
      showed that all the WG formulations (with or without MMT) were more effective
      than both the commercial formulation and the non-formulated ethofumesate,
      whatever the concentration tested. To explain such results, it was proposed that
      WG formulations would enable ethofumesate to be more available and thus more
      effective in inhibiting seed germination, as they would be less prone to be
      leached by water transport due to watering and also less subject to
      photodegradation. CONCLUSION: The use of pesticide formulations based on wheat
      gluten and nanoclays appeared to be a promising strategy both to reduce the
      mobility of pesticides in soil and to protect UV-photosensitive pesticides from
      photodegradation.

PMID- 24323839
TI  - 25th anniversary article: polymer-particle composites: phase stability and
      applications in electrochemical energy storage.
AB  - Polymer-particle composites are used in virtually every field of technology. When
      the particles approach nanometer dimensions, large interfacial regions are
      created. In favorable situations, the spatial distribution of these interfaces
      can be controlled to create new hybrid materials with physical and transport
      properties inaccessible in their constituents or poorly prepared mixtures. This
      review surveys progress in the last decade in understanding phase behavior,
      structure, and properties of nanoparticle-polymer composites. The review takes a
      decidedly polymers perspective and explores how physical and chemical approaches
      may be employed to create hybrids with controlled distribution of particles.
      Applications are studied in two contexts of contemporary interest: battery
      electrolytes and electrodes. In the former, the role of dispersed and aggregated
      particles on ion-transport is considered. In the latter, the polymer is employed
      in such small quantities that it has been historically given titles such as
      binder and carbon precursor that underscore its perceived secondary role.
      Considering the myriad functions the binder plays in an electrode, it is
      surprising that highly filled composites have not received more attention.
      Opportunities in this and related areas are highlighted where recent advances in
      synthesis and polymer science are inspiring new approaches, and where newcomers
      to the field could make important contributions. 

PMID- 24323838
TI  - Continuous drug delivery in Parkinson's disease.
AB  - Development of motor and non-motor complications during the course of Parkinson's
      disease (PD) is a major challenge for therapeutic management. At advanced disease
      stages, patients frequently fluctuate between PD symptoms-such as bradykinesia
      and dyskinesias, in response to fluctuations in drug concentrations. Continuous
      subcutaneous infusion of the dopamine agonist apomorphine or intestinal infusion
      of levodopa reduce such fluctuations in both pharmacokinetics and motor function.
      This is the basis for the concept of continuous drug delivery in PD, and the more
      theoretical concept of continuous dopaminergic stimulation. These expressions are
      sometimes used to describe a treatment that is more continuous in its
      pharmacokinetic profile or that produces more sustained effects, compared with
      immediate-release levodopa, i.e. not only pump treatments. For example, sustained
      release formulations of levodopa or dopamine agonists, transdermal delivery of
      rotigotine, and addition of catechol-O-methyltransferase inhibitors or monoamine
      oxidase-B inhibitors have been developed with the aim to provide more continuous
      drug concentrations, sustained benefits and minimized side effects. Progress has
      been made, but there are still knowledge gaps regarding how these treatment
      alternatives can be optimally used. New treatments are currently being developed
      to provide the continuous drug delivery that is known to successfully alleviate
      motor and non-motor complications. Hopefully, although not yet proven, these new
      methods may also prevent or postpone some of the late-stage complications. 

PMID- 24323840
TI  - Microvascularization and histomorphology of lateral line organs in adult Xenopus
      laevis.
AB  - The microvasculariaztion of the lateral line organs (LLOs) of the adult pipid
      frog, Xenopus laevis was studied by scanning electron microscopy of vascular
      corrosion casts (VCCs) and correlative light microscopy of paraplast embedded
      tissues sections. Scanning electron micrographs of VCCs revealed that each
      neuromast within the LLO rests on a distinct bowl-like capillary network
      (vascular bowl). One to three vascular bowls were supplied by an ascending
      arteriole and drained by a descending venule towards the skin deep dermal
      vascular network. Blood flow regulation mechanisms in form of intimal cushions
      were present at the origin of ascending arterioles supplying LLOs, microvenous
      valves were present at the confluence of deep dermal venules and veins. This
      together with sprouting and nonsprouting angiogenesis (intussusceptive
      microvascular growth) found in vascular bowls demonstrate that in adult Xenopus
      the capillary bed of LLO's still can be adjusted to changing energetic needs.

PMID- 24323842
TI  - Oleuropein as an inhibitor of peroxisome proliferator-activated receptor gamma.
AB  - Oleuropein, the major phenolic compound found in olive leaves and oil, exerts
      antioxidant, anti-inflammatory and anti-atherogenic effects and suppresses the
      adipocyte differentiation in vitro. Herein, we characterized molecular mechanisms
      underlying the anti-adipogenic effects of oleuropein on 3T3-L1 cells and
      adipocytes derived from stromal-vascular fraction of dorsolumbar and gonadal fat
      dissected from mice. We found that oleuropein (>100 MUM) decreased viability of
      preadipocytes proliferating in vitro and did not exerted any cytotoxic effects in
      post-confluent cells after induction of differentiation. Oleuropein (>100 MUM)
      inhibited adipocyte differentiation, suppressed gene expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma), CCAAT-/enhancer-binding
      protein alpha, sterol regulatory element-binding transcription factor 1c and
      fatty acid synthase. Furthermore, we tested ability of oleuropein to regulate of
      PPARgamma-, PPARalpha- or PPARbeta-/PPARdelta-mediated beta-lactamase expression
      in appropriate reporter gene assays. Oleuropein between 10 and 400 MUM
      concentrations did not affect activity of PPARalpha or PPARbeta/delta. Contrary,
      PPARgamma activity, either basal or rosiglitazone activated, was inhibited by
      oleuropein. Our data suggest that oleuropein exerts anti-adipogenic effect
      through direct inhibition of PPARgamma transcriptional activity. 

PMID- 24323843
TI  - Noninvasive positive-pressure ventilation as a weaning strategy for intubated
      adults with respiratory failure.
AB  - BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) provides ventilatory
      support without the need for an invasive airway. Interest has emerged in using
      NPPV to facilitate earlier removal of an endotracheal tube and to decrease
      complications associated with prolonged intubation. OBJECTIVES: We evaluated
      studies in which invasively ventilated adults with respiratory failure of any
      cause (chronic obstructive pulmonary disease (COPD), non-COPD, postoperative,
      nonoperative) were weaned by means of early extubation followed by immediate
      application of NPPV or continued IPPV weaning. The primary objective was to
      determine whether the noninvasive positive-pressure ventilation (NPPV) strategy
      reduced all-cause mortality compared with invasive positive-pressure ventilation
      (IPPV) weaning. Secondary objectives were to ascertain differences between
      strategies in proportions of weaning failure and ventilator-associated pneumonia
      (VAP), intensive care unit (ICU) and hospital length of stay (LOS), total
      duration of mechanical ventilation, duration of mechanical support related to
      weaning, duration of endotracheal mechanical ventilation (ETMV), frequency of
      adverse events (related to weaning) and overall quality of life. We planned
      sensitivity and subgroup analyses to assess (1) the influence on mortality and
      VAP of excluding quasi-randomized trials, and (2) effects on mortality and
      weaning failure associated with different causes of respiratory failure (COPD vs.
      mixed populations). SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (The Cochrane Library, Issue 5, 2013), MEDLINE (January 1966 to
      May 2013), EMBASE (January 1980 to May 2013), proceedings from four conferences,
      trial registration websites and personal files; we contacted authors to identify
      trials comparing NPPV versus conventional IPPV weaning. SELECTION CRITERIA:
      Randomized and quasi-randomized trials comparing early extubation with immediate
      application of NPPV versus IPPV weaning in intubated adults with respiratory
      failure. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trial quality and abstracted data according to prespecified criteria. Sensitivity
      and subgroup analyses assessed (1) the impact of excluding quasi-randomized
      trials, and (2) the effects on selected outcomes noted with different causes of
      respiratory failure. MAIN RESULTS: We identified 16 trials, predominantly of
      moderate to good quality, involving 994 participants, most with chronic
      obstructive pulmonary disease (COPD). Compared with IPPV weaning, NPPV weaning
      significantly decreased mortality. The benefits for mortality were significantly
      greater in trials enrolling exclusively participants with COPD (risk ratio (RR)
      0.36, 95% confidence interval (CI) 0.24 to 0.56) versus mixed populations (RR
      0.81, 95% CI 0.47 to 1.40). NPPV significantly reduced weaning failure (RR 0.63,
      95% CI 0.42 to 0.96) and ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to
      0.43); shortened length of stay in an intensive care unit (mean difference (MD) 
      5.59 days, 95% CI -7.90 to -3.28) and in hospital (MD -6.04 days, 95% CI -9.22 to
      -2.87); and decreased the total duration of ventilation (MD -5.64 days, 95% CI 
      9.50 to -1.77) and the duration of endotracheal mechanical ventilation (MD - 7.44
      days, 95% CI -10.34 to -4.55) amidst significant heterogeneity. Noninvasive
      weaning also significantly reduced tracheostomy (RR 0.19, 95% CI 0.08 to 0.47)
      and reintubation (RR 0.65, 95% CI 0.44 to 0.97) rates. Noninvasive weaning had no
      effect on the duration of ventilation related to weaning. Exclusion of a single
      quasi-randomized trial did not alter these results. Subgroup analyses suggest
      that the benefits for mortality were significantly greater in trials enrolling
      exclusively participants with COPD versus mixed populations. AUTHORS'
      CONCLUSIONS: Summary estimates from 16 trials of moderate to good quality that
      included predominantly participants with COPD suggest that a weaning strategy
      that includes NPPV may reduce rates of mortality and ventilator-associated
      pneumonia without increasing the risk of weaning failure or reintubation.

PMID- 24323841
TI  - Projection neurons of the vestibulo-sympathetic reflex pathway.
AB  - Changes in head position and posture are detected by the vestibular system and
      are normally followed by rapid modifications in blood pressure. These
      compensatory adjustments, which allow humans to stand up without fainting, are
      mediated by integration of vestibular system pathways with blood pressure control
      centers in the ventrolateral medulla. Orthostatic hypotension can reflect altered
      activity of this neural circuitry. Vestibular sensory input to the vestibulo
      sympathetic pathway terminates on cells in the vestibular nuclear complex, which
      in turn project to brainstem sites involved in the regulation of cardiovascular
      activity, including the rostral and caudal ventrolateral medullary regions (RVLM
      and CVLM, respectively). In the present study, sinusoidal galvanic vestibular
      stimulation was used to activate this pathway, and activated neurons were
      identified through detection of c-Fos protein. The retrograde tracer Fluoro-Gold
      was injected into the RVLM or CVLM of these animals, and immunofluorescence
      studies of vestibular neurons were conducted to visualize c-Fos protein and
      Fluoro-Gold concomitantly. We observed activated projection neurons of the
      vestibulo-sympathetic reflex pathway in the caudal half of the spinal, medial,
      and parvocellular medial vestibular nuclei. Approximately two-thirds of the cells
      were ipsilateral to Fluoro-Gold injection sites in both the RVLM and CVLM, and
      the remainder were contralateral. As a group, cells projecting to the RVLM were
      located slightly rostral to those with terminals in the CVLM. Individual
      activated projection neurons were multipolar, globular, or fusiform in shape.
      This study provides the first direct demonstration of the central vestibular
      neurons that mediate the vestibulo-sympathetic reflex.

PMID- 24323844
TI  - Rehabilitation following surgery for lumbar spinal stenosis.
AB  - BACKGROUND: Lumbar spinal stenosis is a common cause of back pain that can also
      give rise to pain in the buttock, thigh or leg, particularly when walking.
      Several possible treatments are available, of which surgery appears to be best at
      restoring function and reducing pain. Surgical outcome is not ideal, and a
      sizeable proportion of patients do not regain good function. No accepted evidence
      based approach to postoperative care is known-a fact thathas prompted this
      review. OBJECTIVES: To determine whether active rehabilitation programmes
      following primary surgery for lumbar spinal stenosis have an impact on functional
      outcomes and whether such programmes are superior to 'usual postoperative care'.
      SEARCH METHODS: We searched the following databases from their first issues to
      March 2013: CENTRAL (The Cochrane Library, most recent issue), the Cochrane Back
      Review Group Trials Register, MEDLINE, EMBASE, CINAHL and PEDro. SELECTION
      CRITERIA: We considered randomised controlled trials (RCTs) that compared the
      effectiveness of active rehabilitation versus usual care in adults (> 18 years of
      age) with confirmed lumbar spinal stenosis who had undergone spinal decompressive
      surgery (with or without fusion) for the first time. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data from the included
      trials by using a predeveloped form. We contacted authors of original trials to
      request additional unpublished data as required. We recorded baseline
      characteristics of participants, interventions, comparisons, follow-up and
      outcome measures to enable assessment of clinical homogeneity. Clinical relevance
      was independently assessed by using the five questions recommended by the
      Cochrane Back Review Group (CBRG), and risk of bias within studies was determined
      by using CBRG criteria.We pooled individual study results in a meta-analysis when
      appropriate. For continuous outcomes, we calculated the mean difference (MD) when
      the same measurement scales were used in all studies and the standardised mean
      difference (SMD) when different measurement scales were used. Whenreported means
      and standard deviations of the outcomes showed that outcome data were skewed, we
      log-transformed data for all studies in the comparison and performed a meta
      analysis on the log-scale. Results of analyses performed on the log-scale were
      converted back to the original scale. We used a fixed-effect inverse variance
      model to measure treatment effect when no substantial evidence of statistical
      heterogeneity was found. When we detected substantial statistical heterogeneity,
      we used a random-effects inverse variance model.The primary outcome measure was
      functional status as measured by a back-specific functional scale. Secondary
      outcomes included measures of leg pain, low back pain and global
      improvement/general health. We considered statistical significance and clinical
      relevance of outcomes. We used the GRADE approach to assess the overall quality
      of evidence for each outcome on the basis of five criteria, for which evidence
      was ranked from high to very low quality, depending on the number of criteria
      met. MAIN RESULTS: Our searches yielded 1,726 results, and a total of three
      studies (N = 373 participants) were included in the review and meta-analysis. All
      studies were deemed to have low risk of bias; no study had unacceptably high
      dropout rates. Also, no unacceptably unbalanced dropout rates, unacceptably low
      adherence rates or non-adherence to the protocol or clearly significant
      unbalanced baseline differences were noted for the primary outcome. Outcomes in
      the short term (within six months postoperative)Evidence of moderate quality from
      three RCTs (N = 340) shows that active rehabilitation is more effective than
      usual care for functional status (log SMD -0.22, 95% confidence interval (CI) 
      0.44 to 0.00, corresponding to an average percentage improvement (reduction in
      standardised functional score) of 20%, 95% CI 0% to 36%) and for reported low
      back pain (log MD -0.18, 95% CI-0.35 to -0.02, corresponding to an average
      percentage improvement (reduction in VAS score) of 16%, 95% CI 2% to 30%). In
      contrast, evidence of low quality suggests that rehabilitation is no more
      effective than usual care for leg pain (log MD -0.17, 95% CI -0.52 to 0.19,
      corresponding to an average percentage improvement (reduction in VAS score) of
      16%, 95% CI 21% worsening to 41% improvement). Low-quality evidence from two RCTs
      (N = 238) indicates that rehabilitation has no additional benefit on general
      health status as compared to usual care (MD 1.30, 95% CI -4.45 to 7.06). Outcomes
      in the long term (at 12 months postoperative)Evidence of moderate quality from
      three RCTs (N = 373) shows that rehabilitation is more effective than usual care
      for functional status (log SMD -0.26, 95% CI -0.46 to -0.05, corresponding to an
      average percentage improvement (reduction in standardised functional score) of
      23%, 95% CI 5% to 37%), for reported low back pain (log MD -0.20, 95% CI -0.36 to
      -0.05, corresponding to an average percentage improvement (reduction in VAS
      score) of 18%, 95% CI 5% to 30%]. Evidence of moderate quality (N = 373) and for
      leg pain (log MD -0.24, 95% CI -0.47 to -0.01, corresponding to an average
      percentage improvement (reduction in VAS score) of 21%, 95% CI 1% to 37%). In
      contrast, evidence of low quality from two studies (N = 273) suggests that
      rehabilitation is no more effective than usual care with respect to improvement
      in general health (MD -0.48, 95% CI -6.41 to 5.4).None of the included papers
      reported any relevant adverse events. AUTHORS' CONCLUSIONS: Evidence suggests
      that active rehabilitation is more effective than usual care in improving both
      short- and long-term (back-related) functional status. Similar findings were
      noted for secondary outcomes, including short-term improvement in low back pain
      and long-term improvement in both low back pain and leg pain, although limited
      impact was observed in relation to improvements in general health status. The
      clinical relevance of these effects is medium to small. Our evaluation is limited
      by the small number of relevant studies identified, and further research is
      required.

PMID- 24323845
TI  - Why is N...Be distance of NH3H(+)...DBeH shorter than that of NH3D(+)...HBeH?
      Paradoxical geometrical isotope effects for partially isotope-substituted
      dihydrogen-bonded isotopomers.
AB  - The partial isotope substitution for the change of geometrical parameters,
      interaction energies, and nuclear magnetic shielding tensors (sigma) of
      dihydrogen-bonded NH3X(+)...YBeH (X, Y = H, D, and T) systems is analyzed. Based
      on the theoretical calculation, the distance between heavy atoms RN...Be of
      NH3H(+) ...DBeH is clearly found to be shorter than that in NH3D(+)...HBeH. Such
      apparently paradoxical geometrical isotope effect (GIE) on RN...Be is revealed by
      the cooperative effect of two kinds of (1) primary covalent-bonded GIE and (2)
      secondary dihydrogen-bonded one. We have demonstrated that (1) the covalent bond
      lengths become shorter by heavier isotope-substitution and (2) the dihydrogen
      bonded distance RX...Y becomes shorter by heavier Y and lighter X isotope
      substitution due to the difference of electronic structure reflected by the
      nuclear distribution. We have also found that interaction energy of
      NH3H(+)...DBeH is stronger than that of NH3D(+)...HBeH and isotopic deshielding
      effect of magnetic shielding becomes large in lighter isotope.

PMID- 24323846
TI  - Sono-assembly of highly biocompatible polysaccharide capsules for hydrophobic
      drug delivery.
AB  - Cells like sugar. General synthesis and potential of intracellular hydrophobic
      drug delivery of single-component polysaccharide capsules are pursued. The
      capsules can be generally assembled through hydrogen bonding networks but show
      striking shell robustness. The evidenced cell internalization, stimuli
      responsiveness to local pH changes and high biocompatibilities of the capsules
      specifically favor their potential intracellular drug delivery. 

PMID- 24323847
TI  - Tuning cellular response to nanoparticles via surface chemistry and aggregation.
AB  - The aggregation of gold nanoparticles (Au NPs) in cell media is a common
      phenomenon that can influence NP-cell interactions. Here, we control Au NP
      aggregation in cell media and study the impact of Au NP aggregation on human
      dermal fibroblast (HDF) cells. By first adding Au NPs to fetal bovine serum (FBS)
      and then subsequently to a buffer, aggregation can be avoided. Aggregation of Au
      NPs also can be avoided by coating Au NPs with other biomolecules such as lipids.
      The aggregation state of the Au NPs influences cellular toxicity and Au NP
      uptake: non-aggregated cationic Au NPs are four-fold less toxic to HDF cells than
      aggregated cationic Au NPs, and the uptake of non-aggregated anionic citrate Au
      NPs is three orders of magnitude less than that of aggregated citrate Au NPs.
      Upon uptake of Au NPs, cellular F-actin fiber formation is disrupted and actin
      dots are predominant. When lipid-coated Au NPs are doped with a fluorescent lipid
      (F-lipid) and incubated with HDF cells, the fluorescence from the F-lipid was
      found throughout the cell, showing that lipids can dissociate from the Au NP
      surface upon entering the cell. 

PMID- 24323852
TI  - Selective synthesis of silver nanoparticles onto potassium hexaniobate:
      structural organisation with bactericidal properties.
AB  - Silver-based nanocomposites are known to act as biocides against a series of
      microorganisms and are largely studied as an alternative to substitute
      conventional antibiotics that show decreasing efficacy. In this work, an eco
      friendly method to synthesize silver nanoparticles assembled on the surface of
      hexaniobate crystals is reported. By means of ion exchange, K(+) ions of layered
      potassium hexaniobate were partially substituted by Ag(+) ions and the resulting
      material was exposed to UV light. The irradiation allowed the reduction of silver
      ions with consequent formation of silver nanoparticles located only on the
      hexaniobate surface, whereas Ag(+) ions located in the interlayer space remained
      in the ionic form. Increasing UV-light exposure times allowed controlling of the
      silver nanoparticle size. The antibacterial effects of the pristine potassium
      hexaniobate and of silver-containing hexaniobate samples were tested against
      Escherichia coli (E. coli). The antibacterial efficacy was determined to be
      related to the presence of silver in hexaniobate. An increasing activity against
      E. coli was observed with the decrease in silver nanoparticles size, suggesting
      that silver nanoparticles of distinct sizes interact differently with bacterial
      cell walls. 

PMID- 24323853
TI  - A rapid freeze-quench setup for multi-frequency EPR spectroscopy of enzymatic
      reactions.
AB  - Electron paramagnetic resonance (EPR) spectroscopy in combination with the rapid
      freeze-quench (RFQ) technique is a well-established method to trap and
      characterize intermediates in chemical or enzymatic reactions at the millisecond
      or even shorter time scales. The method is particularly powerful for mechanistic
      studies of enzymatic reactions when combined with high-frequency EPR (nu>=90
      GHz), which permits the identification of substrate or protein radical
      intermediates by their electronic g values. In this work, we describe a new
      custom-designed micro-mix rapid freeze-quench apparatus, for which reagent
      volumes for biological samples as small as 20 MUL are required. The apparatus was
      implemented with homemade sample collectors appropriate for 9, 34, and 94 GHz EPR
      capillaries (4, 2, and 0.87 mm outer diameter, respectively) and the performance
      was evaluated. We demonstrate the application potential of the RFQ apparatus by
      following the enzymatic reaction of PpoA, a fungal dioxygenase producing
      hydro(pero)xylated fatty acids. The larger spectral resolution at 94 GHz allows
      the discernment of structural changes in the EPR spectra, which are not
      detectable in the same samples at the standard 9 GHz frequency. 

PMID- 24323854
TI  - Synthesis and third-order nonlinear optical properties of triphenylene
      derivatives modified by click chemistry.
AB  - A series of asymmetric triphenylene derivatives containing typical D-pi-A
      structures is successfully synthesized by means of [2+2] cycloaddition
      cycloreversion click reactions. The photophysical and electrochemical properties,
      as well as the click reactions, are characterized by means of UV/Vis absorption
      spectroscopy, cyclic voltammetry, and DFT modulations. In addition, the third
      order nonlinear properties, including the nonlinear absorption and the nonlinear
      susceptibilities, are investigated by using Z-scan techniques. A typical reverse
      saturable absorption-saturable absorption behavior is observed for the third
      order nonlinear absorption, with the third-order nonlinear susceptibilities of
      the compounds being 1.05*10(-12) , -1.50*10(-12) , and -0.52*10(-12) esu,
      respectively. 

PMID- 24323855
TI  - Spectroscopic properties and upconversion studies in Ho(3+) /Yb(3+) Co-doped
      calcium scandate with spectrally pure green emission.
AB  - The optical properties of a Ho(3+) /Yb(3+) co-doped CaSc2 O4 oxide material are
      investigated in detail. The spectral properties are described as a function of
      doping concentrations. The efficient Yb(3+) ->Ho(3+) energy transfer is observed.
      The transfer efficiency approaches 50 % before concentration quenching. The
      concentration-optimized sample exhibits a strong green emission accompanied with
      a weak red emission, showing perfect green monochromaticity. The results of the
      spectral distribution, power dependence, and lifetime measurements are presented.
      The green, red, and near-infrared (NIR) emissions around 545, 660, and 759 nm are
      assigned to the (5) F4 +(5) S2 ->(5) I8 , (5) F5 ->(5) I8 , and (5) F4 +(5) S2 
      >(5) I7 transitions of Ho(3+) , respectively. The detailed study reveals the
      upconversion luminescence mechanism involved in a novel Ho(3+) /Yb(3+) co-doped
      CaSc2 O4 oxide material. 

PMID- 24323856
TI  - In situ generation of superoxide anion radical in aqueous medium under ambient
      conditions.
AB  - In the recent decades superoxide [O(2-.) ] has become the subject of considerable
      interest. Nonetheless, generation of superoxide compounds is still a substantial
      challenge. The standard methods for synthesis of superoxide derivatives are
      either through the oxidation of molten alkali metals with hot air or by using
      electrolytic reduction of oxygen in aprotic solvent such as dimethylformamide. No
      methodology is available for the generation of superoxides in protic solutions
      and particularly not in water. We propose a new in situ method for alkali
      superoxide preparation by using sodium hydroxide and hydrogen peroxide at room
      temperature and in aqueous solution. 

PMID- 24323857
TI  - Intracerebral hemorrhage: mechanisms and therapies.

PMID- 24323858
TI  - Treatment of intracerebral hemorrhage-is the glass half full or half empty?

PMID- 24323859
TI  - Neonatal intracerebral hemorrhage: mechanisms, managements, and the outcomes.
AB  - Intracerebral hemorrhage is a multifactorial disorder with heterogeneous
      etiologies and potentially long-term debilitating outcomes. We review all
      available evidence regarding the current strategies for management of
      intracerebral hemorrhage. It is clear that prompt detection and treatment does
      affect the outcome; nevertheless, prevention of intracerebral hemorrhage remains
      the best strategy. 

PMID- 24323860
TI  - Intracerebral hemorrhage: clinical overview and pathophysiologic concepts.
AB  - Intracerebral hemorrhage is by far the most destructive form of stroke. Apart
      from the management in a specialized stroke or neurological intensive care unit
      (NICU), no specific therapies have been shown to consistently improve outcomes
      after ICH. Current guidelines endorse early aggressive optimization of
      physiologic derangements with ventilatory support when indicated, blood pressure
      control, reversal of any preexisting coagulopathy, intracranial pressure
      monitoring for certain cases, osmotherapy, temperature modulation, seizure
      prophylaxis, treatment of hyerglycemia, and nutritional support in the stroke
      unit or NICU. Ventriculostomy is the cornerstone of therapy for control of
      intracranial pressure patients with intraventricular hemorrhage. Surgical
      hematoma evacuation does not improve outcome for more patients, but is a
      reasonable option for patients with early worsening due to mass effect due to
      large cerebellar or lobar hemorrhages. Promising experimental treatments
      currently include ultra-early hemostatic therapy, intraventricular clot lysis
      with thrombolytics, pioglitazone, temperature modulation, and deferoxamine to
      reduce iron-mediated perihematomal inflammation and tissue injury. 

PMID- 24323861
TI  - The Molecular Mechanisms that Promote Edema After Intracerebral Hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating type of stroke with no effective
      therapies. Clinical advances in ICH treatment are limited by an incomplete
      understanding of the molecular mechanisms responsible for secondary injury and
      poor outcome. Increasing evidence suggests that cerebral edema is a major
      contributor to secondary injury and poor outcome in ICH. ICH activates specific
      signaling pathways that promote edema and damage neuronal tissue. By increasing
      our understanding of these pathways, we may be able to target them
      pharmaceutically to reduce edema in ICH patients. In this review, we focus on
      three major signaling pathways that promote edema after ICH: (1) the coagulation
      cascade and thrombin, (2) the inflammatory response and matrix
      metalloproteinases, and (3) the complement cascade and hemoglobin toxicity. We
      will describe the experimental evidence that confirms these pathways promote
      edema in ICH, discuss potential targets for new therapies, and comment on
      important directions for future research. 

PMID- 24323862
TI  - Excitatory and Mitogenic Signaling in Cell Death, Blood-brain Barrier Breakdown,
      and BBB Repair after Intracerebral Hemorrhage.
AB  - Intracerebral hemorrhage (ICH) results in the release of a large number of
      endogenous molecules, including glutamate, Ca(2+), ROS, thrombin, heme, iron, TNF
      alpha, and others. These molecules participate in excitatory and mitogenic
      signaling transduction in which N-methyl-D-aspartate (NMDA) receptors and Src
      family kinases (SFKs) are implicated. Mitogenic signaling initiates the cell
      cycle for normal cell division of microglia and neural progenitor cells, whereas
      aberrant mitogenic signaling causes toxicity, killing neurons, astrocytes, and
      brain microvascular endothelial cells in neurological diseases including ICH. In
      this review, we summarize (1) how SFKs modulate NMDA receptors to kill neurons
      following ICH and (2) how SFKs modulate mitogenic signaling transduction to kill
      neurons and play a role in disrupting the blood-brain barrier (BBB) immediately
      following ICH and in repairing the BBB during the recovery phases weeks following
      ICH. 

PMID- 24323863
TI  - Chemokines and their receptors in intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating clinical event which results in a
      high rate of disability and death. At present, no effective treatment is
      available for ICH. Accumulating evidence suggests that inflammatory responses
      contribute significantly to the ICH-induced secondary brain outcomes. During ICH,
      inflammatory cells accumulate at the ICH site attracted by gradients of
      chemokines. This review summarizes recent progress in ICH studies and the
      chemoattractants that act during the injury and focuses on and introduces the
      basic biology of the chemokine monocyte chemoattractant protein-1 (MCP1) and its
      role in the progression of ICH. Better understanding of MCP1 signaling cascade
      and the compensation after its inhibition could shed light on the development of
      effective treatments for ICH. 

PMID- 24323864
TI  - Astrogliosis: a target for intervention in intracerebral hemorrhage?
AB  - Intracerebral hemorrhage (ICH) is a debilitating neurological injury, accounting
      for 10-15 % of all strokes. Despite neurosurgical intervention and supportive
      care, the 30-day mortality rate remains ~50 %, with ICH survivors frequently
      displaying neurological impairments and requiring long-term assisted care.
      Unfortunately, the lack of medical interventions to improve clinical outcomes has
      led to the notion that ICH is the least treatable form of stroke. Hence,
      additional studies are warranted to better understand the pathophysiology of ICH.
      Astrogliosis is an underlying astrocytic response to a wide range of brain
      injuries and postulated to have both beneficial and detrimental effects. However,
      the molecular mechanisms and functional roles of astrogliosis remain least
      characterized following ICH. Herein, we review the functional roles of
      astrogliosis in brain injuries and raise the prospects of therapeutically
      targeting astrogliosis after ICH. 

PMID- 24323865
TI  - TOMM40 in Cerebral Amyloid Angiopathy Related Intracerebral Hemorrhage:
      Comparative Genetic Analysis with Alzheimer's Disease.
AB  - Cerebral amyloid angiopathy (CAA) related intracerebral hemorrhage (ICH) is a
      devastating form of stroke with no known therapies. Clinical, neuropathological,
      and genetic studies have suggested both overlap and divergence between the
      pathogenesis of CAA and the biologically related condition of Alzheimer's disease
      (AD). Among the genetic loci associated with AD are APOE and TOMM40, a gene in
      close proximity to APOE. We investigate here whether variants within TOMM40 are
      associated with CAA-related ICH and CAA neuropathology. Using cohorts from the
      Massachusetts General Hospital (MGH) and the Alzheimer's Disease Neuroimaging
      Initiative (ADNI), we designed a comparative analysis of high-density SNP
      genotype data for CAA-related ICH and AD. APOE epsilon4 was associated with CAA
      related ICH and AD, while APOE epsilon2 was protective in AD but a risk factor
      for CAA. A total of 14 SNPs within TOMM40 were associated with AD (p < 0.05 after
      multiple testing correction), but not CAA-related ICH (all p > 0.20); as a
      result, all AD-associated SNPs within TOMM40 showed heterogeneity of effect in
      CAA-related ICH (BD p < 0.001). Analysis of CAA neuropathology in the Religious
      Orders Study (ROS) and Rush Memory and Aging Project (MAP), however, found that
      neuritic plaque, diffuse plaque burden, and vascular amyloid burden associated
      with all TOMM40 SNPs (p < 0.02). These results suggest that alterations in TOMM40
      can promote vascular as well as plaque amyloid deposition, but not the full
      pathogenic pathway leading to CAA-related ICH. 

PMID- 24323866
TI  - Hyperglycemia and outcome in intracerebral hemorrhage: from bedside to bench-more
      study is needed.
AB  - Hyperglycemia on admission has been associated with poor outcome after
      intracerebral hemorrhage (ICH). However, the mechanistic links between
      hyperglycemia and poor outcome are not fully elucidated. We sought to determine
      the relationship between the serum glucose levels during the first 72 h after
      ICH, and evolution of hematoma and perihematomal edema (PHE), and functional
      outcome at 3 months and performed a retrospective review of prospectively
      collected data from 135 consecutive ICH patients. Patients were divided into two
      groups based on their mean glucose level-high (>=150 mg/dl) vs. controlled (<150
      mg/dl). We used Chi-square test and multiple logistic regressions to assess the
      relationship between glucose level and outcome variables, including hematoma
      expansion (HE), PHE growth, and modified Rankin Scale (mRS) score at 3 months.
      The mean 72-h glucose level was 123 +/- 16 for the controlled group and 190 +/-
      48 mg/dl for the high-glucose group. The corresponding rates of HE were 23.4 vs.
      25.9 % (unadjusted p = 0.80; adjusted p = 0.08); PHE growth, 31.3 vs. 29.6 %
      (unadjusted p = 0.88; adjusted p = 0.39); and poor outcome at 3 months, defined
      as mRS score of >=3, was 54 vs. 71 % (unadjusted p = 0.06; adjusted p = 0.89). On
      multivariate analyses, the ICH score emerged as the major predictor for poor
      outcome, but not glucose. In conclusion, we found a trend for an association
      between mean 72 h glucose levels and poor outcome at 3 months, but this effect
      attenuated after adjusting for the ICH score. High glucose was not associated
      with HE or PHE growth. More preclinical and clinical studies are needed to
      elucidate the role of hyperglycemia in ICH before embarking on large and costly
      clinical trials of tight glucose control in ICH patients. 

PMID- 24323867
TI  - Depletion of GR-1-Positive Cells Is Associated with Reduced Neutrophil
      Inflammation and Astrocyte Reactivity after Experimental Intracerebral
      Hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is the stroke subtype with the highest mortality
      and morbidity with 25% of patients dying within the first 48 h and a high
      incidence of poor outcomes. Because of high early mortality rates, an
      understanding of acute brain injury mechanisms is essential. In this study, we
      have investigated the putative role of acute inflammation in brain injury after
      experimental ICH. We depleted GR-1(+) cells in mice by intraperitoneal
      administration of anti-GR-1 antibody or normal rat serum (control). We then
      induced ICH by infusion of autologous whole blood into the striatum and compared
      functional outcome and brain injury markers between the two groups. We found that
      administration of anti-GR-1 antibody led to a profound decrease in circulating GR
      1(+) cells (1.5 +/- 0.34% vs. 50.3 +/- 8.3% of CD45(+) cells, p <= 0.01) and that
      brain neutrophils decreased by approximately 50% (p <= 0.05). We observed a
      reduction in astrocyte immunoreactivity in the GR-1(+) cell-depleted group (p <=
      0.05). Conversely, we did not find attenuation of brain edema or differences in
      behavioral deficits between the two groups. In summary, our results are promising
      and suggest that larger studies or different neutrophil manipulations may produce
      greater attenuation of injury after ICH. 

PMID- 24323868
TI  - Micro-computed tomography for hemorrhage disruption of mouse brain vasculature.
AB  - The use of genetic engineering to develop important neuropathological mouse
      models has made cerebrovascular imaging essential for the investigation of
      numerous brain disorders, especially cerebrovascular disorders, such as
      aneurysms, arteriovenous malformations, and ischemic and hemorrhagic stroke. New
      laboratory-based X-ray microimagers exist that provide easy access, reliable
      operation, and performance previously found only in synchrotron-based
      instruments. Here, we reported a novel approach using such a system to detect
      intracerebral hemorrhage and resultant cerebrovascular pathology. Adult male
      C57BL/6 mice (n = 12) underwent 30 MUl autologous blood injection into the right
      basal ganglia region. After sacrificing the animals and vascular perfusion with
      Microfil(r) MV-122 Yellow to opacify vascular and microvascular structures, the
      brain was post-fixed and partially hydrated for 3D imaging with a MicroXCT-400(r)
      at 30 KeV and 2-MUm resolution. Tomographic reconstruction of high-resolution
      microimages was accomplished with Amira(r) software. High-quality 3D images
      included cerebrocortical microvessels, the circle of Willis, the sagittal sinus,
      transverse sinus, and other arterial and venous systems. In the ipsilateral
      hemisphere, there clearly were early-stage vasodilatation and later-stage
      neovascularization. Very high-resolution, laboratory-based, X-ray micro-CT
      contrast imaging can accomplish sensitive quantifications of normal and
      pathological small cerebrovascular changes, especially in hemorrhagic stroke and
      subsequent hemorrhage-induced neovascularization. 

PMID- 24323869
TI  - Scale-down models to optimize a filter train for the downstream purification of
      recombinant pharmaceutical proteins produced in tobacco leaves.
AB  - The extraction of biopharmaceutical proteins from intact leaves involves the
      release of abundant particulate contaminants that must be removed economically
      from the process stream before chromatography, for example, using disposable
      filters that comply with good manufacturing practice. We therefore scaled down an
      existing 200-kg process for the purification of two target proteins from tobacco
      leaves (the monoclonal antibody 2G12 and the fluorescent protein DsRed, as
      monitored by surface plasmon resonance spectroscopy and fluorescence imaging,
      respectively) and screened different materials on the 2-kg scale to reduce the
      number of depth filtration steps from three to one. We assessed filter cost and
      capacity, filtrate turbidity, and protein recovery when the filter materials were
      challenged with extracts from different tobacco varieties and related species
      grown in soil or rockwool. PDF4 was consistently the most suitable depth filter
      because it was the least expensive, it did not interact significantly with the
      target proteins, and it had the greatest overall capacity. The filter capacity
      was generally reduced when plants were grown in rockwool, but this substrate has
      a low bioburden, thus improving process safety. Our data concerning the
      clarification of plant extracts will help in the design of more cost-effective
      downstream processes and accelerate their development. 

PMID- 24323871
TI  - Essential oil composition of Aegle marmelos (L.) Correa: chemotypic and seasonal
      variations.
AB  - BACKGROUND: Aegle marmelos (L.) Correa is a sacred medicinal and nutraceutical
      tree of India. The present study planned to explore the chemotypic and seasonal
      variability of the leaf essential oil of A. marmelos from north India for proper
      industrial utilization. RESULTS: The essential oil yield varied from 0.37% to
      0.80% in leaves of A. marmelos populations. Analysis of the essential oils by gas
      chromatography and gas chromatography-mass spectrometry, and the subsequent
      classification by statistical analysis showed three types of chemical
      compositions for A. marmelos with significant variations in their terpenoid
      compositions. Major components of the essential oils were limonene (31.0-90.3%),
      alpha-phellandrene (<0.05-43.5%), (E)-beta-ocimene (0.7-7.9%), alpha-pinene
      (<0.05-7.5%), (E)-caryophyllene (0.5-5.3%), beta-elemene (<0.05-4.2%) and
      germacrene B (0.0-3.3%). In addition to this, essential oil of a locally growing
      A. marmelos population was also investigated for seasonal variations. The
      essential oil yield in this population varied from 0.37% to 0.82% during
      different seasons. Major constituents, namely alpha-phellandrene (35.8-49.8%),
      limonene (24.7-34.3%), (E)-beta-ocimene (4.2-10.0%) and alpha-pinene (6.0-8.0%),
      showed considerable variations due to season of collection. CONCLUSIONS: The
      growing location and harvesting season had a close relation to yield and quality
      of A. marmelos leaf essential oil. The results obtained are of significance for
      determining a suitable time for harvesting A. marmelos leaves.

PMID- 24323872
TI  - Dorsal hump morphology in pink salmon (Oncorhynchus gorbuscha).
AB  - Mature male Pacific salmon (Genus Oncorhynchus) develop a dorsal hump, as a
      secondary male sexual characteristic, during the spawning period. Previous gross
      anatomical studies have indicated that the dorsal humps of salmon are mainly
      composed of cartilaginous tissue (Davidson [1935] J Morphol 57:169-183.) However,
      the histological and biochemical characteristics of such humps are poorly
      understood. In this study, the detailed microstructures and components of the
      dorsal humps of pink salmon were analyzed using histochemical techniques and
      electrophoresis. In mature males, free interneural spines and neural spines were
      located in a line near to the median septum of the dorsal hump. No cartilaginous
      tissue was detected within the dorsal hump. Fibrous and mucous connective tissues
      were mainly found in three regions of the dorsal hump: i) the median septum, ii)
      the distal region, and iii) the crescent-shaped region. Both the median septum
      and distal region consisted of connective tissue with a high water content, which
      contained elastic fibers and hyaluronic acid. It was also demonstrated that the
      lipid content of the dorsal hump connective tissue was markedly decreased in the
      mature males compared with the immature and maturing males. Although, the
      crescent-shaped region of the hump consisted of connective tissue, it did not
      contain elastic fibers, hyaluronic acid, or lipids. In an ultrastructural
      examination, it was found that all of the connective tissues in the dorsal hump
      were composed of collagen fibers. Gel electrophoresis of collagen extracts from
      these tissues found that the collagen in the dorsal hump is composed of Type I
      collagen, as is the case in salmon skin. These results indicate that in male pink
      salmon the dorsal hump is formed as a result of an increase in the amount of
      connective tissue, rather than cartilage, and the growth of free interneural
      spines and neural spines.

PMID- 24323870
TI  - Genetic association analyses of nitric oxide synthase genes and neural tube
      defects vary by phenotype.
AB  - Neural tube defects (NTDs) are caused by improper neural tube closure during the
      early stages of embryonic development. NTDs are hypothesized to have a complex
      genetic origin and numerous candidate genes have been proposed. The nitric oxide
      synthase 3 (NOS3) G594T polymorphism has been implicated in risk for spina
      bifida, and interactions between that single nucleotide polymorphism (SNP) and
      the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have also been
      observed. To evaluate other genetic variation in the NO pathway in the
      development of NTDs, we examined all three NOS genes: NOS1, NOS2, and NOS3. Using
      3109 Caucasian samples in 745 families, we evaluated association in the overall
      dataset and within specific phenotypic subsets. Haplotype tagging SNPs in the NOS
      genes were tested for genetic association with NTD subtypes, both for main
      effects as well as for the presence of interactions with the MTHFR C677T
      polymorphism. Nominal main effect associations were found with all subtypes,
      across all three NOS genes, and interactions were observed between SNPs in all
      three NOS genes and MTHFR C677T. Unlike the previous report, the most significant
      associations in our dataset were with cranial subtypes and the AG genotype of
      rs4795067 in NOS2 (p = 0.0014) and the interaction between the rs9658490 G allele
      in NOS1 and MTHFR 677TT genotype (p = 0.0014). Our data extend the previous
      findings by implicating a role for all three NOS genes, independently and through
      interactions with MTHFR, in risk not only for spina bifida, but all NTD subtypes.

PMID- 24323873
TI  - Fabrication of silicon nanowire arrays by macroscopic galvanic cell-driven metal
      catalyzed electroless etching in aerated HF solution.
AB  - Macroscopic galvanic cell-driven metal catalyzed electroless etching (MCEE) of
      silicon in aqueous hydrofluoric acid (HF) solution is devised to fabricate
      silicon nanowire (SiNW) arrays with dissolved oxygen acting as the one and only
      oxidizing agent. The key aspect of this strategy is the use of a graphite or
      other noble metal electrode that is electrically coupled with silicon substrate. 

PMID- 24323875
TI  - School-aged and adolescent children's experience when a parent has non-terminal
      cancer: a systematic review and meta-synthesis of qualitative studies.
AB  - OBJECTIVE: The purpose of this study was to systematically review and synthesise
      qualitative studies pertinent to male and female school-aged and adolescent
      children's experience when a parent is diagnosed with non-terminal cancer.
      METHODS: A rigorous systematic review and meta-synthesis process were conducted.
      Seven computerised databases were searched, and 2027 articles were retrieved.
      After screening the titles and abstracts, full texts of 24 articles were
      critically appraised, and finally, 16 articles were further analysed and
      synthesised with a thematic-synthesis approach. RESULTS: Five themes were
      identified: being informed of parental cancer, emotional concerns, changes in
      daily life, seeking factual information and seeking emotional support. As
      indicated in the results, most children had been informed of the parent's
      diagnosis of cancer. They suffered from a wide range of concerns when facing the
      situation, and their lives had been interrupted to different degrees. In order to
      cope with the event, children adopted various strategies. Their information and
      support needs were reported to have been poorly met. CONCLUSIONS: This systematic
      review provides insight into the scenario of children living with a parent with
      non-terminal cancer and indicates some suggestions for future studies. The
      experience of children when the father has cancer should be further explored.
      Short-term and long-term impacts of parental cancer on children, especially young
      children within different cultural contexts, should be investigated to help
      health care professionals provide individualised assistance to those children.

PMID- 24323874
TI  - The role of sex differences in autophagy in the heart during coxsackievirus B3
      induced myocarditis.
AB  - Under normal conditions, autophagy maintains cardiomyocyte health and integrity
      through turnover of organelles. During stress, oxygen and nutrient deprivation,
      or microbial infection, autophagy prolongs cardiomyocyte survival. Sex
      differences in induction of cell death may to some extent explain the disparity
      between the sexes in many human diseases. However, sex differences in gene
      expression, which regulate cell death and autophagy, were so far not taken in
      consideration to explain the sex bias of viral myocarditis. Coxsackievirus B3
      (CVB3)-induced myocarditis is a sex-biased disease, with females being
      substantially less susceptible than males and sex hormones largely determine this
      bias. CVB3 was shown to induce and subvert the autophagosome for its optimal
      viral RNA replication. Gene expression analysis on mouse and human, healthy and
      CVB3-infected, cardiac samples of both sexes, suggests sex differences in
      autophagy-related gene expression. This review discusses the aspects of sex bias
      in autophagy induction in cardiomyocytes. 

PMID- 24323884
TI  - Polyarginine induces an antitumor immune response through binding to toll-like
      receptor 4.
AB  - A novel function of polyarginine as an activator of the immune system is
      reported. Single-molecule fluorescence imaging and single-molecule force
      measurements demonstrate that polyarginine binds specifically to the toll-like
      receptor 4 (TLR4), inducing receptor dimerization and activation. Moreover,
      polyarginine induced immune activation inhibits tumor growth. These results
      suggest the potential use of polyarginine for cancer immunotherapy. 

PMID- 24323885
TI  - Decoding the components of dynamics in three-domain proteins.
AB  - In this study, we examine the feasibility and limitations of describing the
      motional behavior of three-domain proteins in which the domains are linearly
      connected. In addition to attempting the determination of the internal and
      overall reorientational correlation times, we investigate the existence of
      correlations in the motions between the three domains. Since in linearly arranged
      three-domain proteins, there are typically no experimental data that can directly
      report on motional correlation between the first and the third domain, we address
      this question by dynamics simulations. Two limiting cases occur: (1) for weak
      repulsive potentials and (2) when strong repulsive potentials are applied between
      sequential domains. The motions of the terminal domains become correlated in the
      case of strong interdomain repulsive potentials when these potentials do not
      allow the angle between the sequential domains to be smaller than about 60
      degrees . Using the model-free (MF) and extended MF formalisms of Lipari and
      Szabo, we find that the motional behavior can be separated into two components;
      the first component represents the concerted overall motion of the three domains,
      and the second describes the independent component of the motion of each
      individual domain. We find that this division of the motional behavior of the
      protein is maintained only when their timescales are distinct and can be made
      when the angles between sequential domains remain between 60 degrees  and 160
      degrees . In this work, we identify and quantify interdomain motional
      correlations.

PMID- 24323886
TI  - Planned elective repeat caesarean section versus planned vaginal birth for women
      with a previous caesarean birth.
AB  - BACKGROUND: When a woman has had a previous caesarean birth, there are two
      options for her care in a subsequent pregnancy: planned elective repeat caesarean
      or planned vaginal birth. While there are risks and benefits for both planned
      elective repeat caesarean birth and planned vaginal birth after caesarean (VBAC),
      current sources of information are limited to non-randomised cohort studies.
      Studies designed in this way have significant potential for bias and consequently
      conclusions based on these results are limited in their reliability and should be
      interpreted with caution. OBJECTIVES: To assess, using the best available
      evidence, the benefits and harms of a policy of planned elective repeat caesarean
      section with a policy of planned VBAC for women with a previous caesarean birth.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 September 2013) and reference lists of retrieved studies. SELECTION
      CRITERIA: Randomised controlled trials with reported data that compared outcomes
      in mothers and babies who planned a repeat elective caesarean section with
      outcomes in women who planned a vaginal birth, where a previous birth had been by
      caesarean. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial quality and extracted data. MAIN RESULTS: Two randomised trials
      involving 320 women and their infants were included. However, data for maternal
      and infant clinical outcomes were available from one trial with very low event
      rates, involving 22 women only.For the primary outcomes maternal death or serious
      morbidity (one study; 22 women; risk ratio (RR) not estimable), and infant death
      or serious morbidity (one study; 22 women; RR not estimable), there were no
      statistically significant differences between planned caesarean birth and planned
      vaginal birth identified. AUTHORS' CONCLUSIONS: Planned elective repeat caesarean
      section and planned VBAC for women with a prior caesarean birth are both
      associated with benefits and harms. Evidence for these care practices is largely
      drawn from non-randomised studies, associated with potential bias. Any results
      and conclusions must therefore be interpreted with caution. Randomised controlled
      trials are required to provide the most reliable evidence regarding the benefits
      and harms of both planned elective repeat caesarean section and planned vaginal
      birth for women with a previous caesarean birth.

PMID- 24323887
TI  - High prevalence of depressive symptoms in well-controlled adolescents with type 1
      diabetes treated with continuous subcutaneous insulin infusion.
AB  - BACKGROUND: Researchers report co-morbid depressive symptoms in children with
      poorly controlled type 1 diabetes (T1D). However, excellent diabetes control may
      be associated with emotional distress as well. The aim of this study was to
      evaluate the prevalence of depressive symptoms in T1D children with HbA1c <7.5%
      and >= 7.5% treated with insulin pump. METHODS: A total of 372 children (186
      girls) with a mean age of 14.2 +/- 2.0 years and mean diabetes duration of 5.3 +/
      3.5 years were included. All subjects were treated for T1D for a minimum of 1
      year. Children filled out a Polish version of the Children's Depression Inventory
      (CDI) and answered questions in the Quality of Life Questionnaire. Statistical
      analysis was made using Student's t-test, Mann-Whitney U-test, Fisher's exact
      test and Spearman's rank correlation. RESULTS: Eighteen per cent (31/177) of
      participants with HbA1c <7.5% and 21% (41/195) with HbA1c >= 7.5% reported
      depressive symptoms (CDI scores >= 13). Adolescents with HbA1c <7.5% and CDI >=
      13 had higher total insulin dose (p = 0.039) and longer diabetes duration (p =
      0.043) than subjects with CDI < 13. There was no difference in prevalence of
      depressive symptoms among patients with HbA1c >= 7.5% and HbA1c <7.5% (odds ratio
      [1.25 95% confidence interval (CI) 0.75-2.11], p = 0.432). In both groups,
      adolescents with CDI >= 13 had worse quality of life than those with CDI < 13 (p
      < 0.0001). CONCLUSIONS: In both groups, one in five adolescents with either good
      or poor glycemic control had depressive symptoms compared with <7% in subjects
      without diabetes. Long-lasting T1D significantly increased the risk of depressive
      symptoms in well-controlled youth. Depressive symptoms strongly affected the
      quality of life regardless of diabetes control.

PMID- 24323889
TI  - Physiological and pathological relevance of secretory microRNAs and a perspective
      on their clinical application.
AB  - MicroRNAs (miRNAs) have attracted significant attention because of their
      important roles in a variety of physiological and pathological processes. Recent
      studies have shown that many cell types secrete miRNAs by packaging them into
      lipid-bilayered small vesicles called exosomes. Furthermore, exosomal miRNAs
      travel between cells, exert their RNAi effects in the recipient cells, and play
      important roles in various biological processes. In this article, we will
      summarize and describe the latest studies on exosomal miRNAs by focusing on their
      roles in cancer progression, immune regulation, and tissue repair. We will also
      provide a perspective on the clinical applications of this research field.

PMID- 24323888
TI  - Vitamin supplementation benefits in master athletes.
AB  - Master athletes are more than 35 years of age and continue to train as hard as
      their young counterparts despite the aging process. All life long, they are
      capable of accomplishing exceptional sporting performances. For these
      participants in endurance events, matching energy intake and expenditure is
      critical to maintain health and performance. The proportions of carbohydrate,
      fat, and protein must be optimized to provide enough calories to sustain the
      energy requirements of competition or training, and for recovery. In addition,
      endurance athletes must include adequate vitamins and minerals in their diets to
      maintain healthy immune function. Vitamins and minerals may be sufficient in the
      diets of endurance athletes, who have a high energy intake. This would make it
      unnecessary to use vitamin and mineral supplements. Furthermore, one major
      limitation for these athletes is the management of oxidative stress, which, when
      in excess, can be deleterious for the organism. For individuals exposed to
      oxidative stress, micronutritional supplementations rich in vitamins and minerals
      can be also an alternative strategy. Although these supplementations are
      increasingly used by master athletes, very few data are available on their
      effects on oxidative stress, muscle recovery, and physical performance. The
      potential benefits of supplement use in athletes are thus questionable. Some
      studies indicate no benefits, while others highlight potential negative side
      effects of vitamin supplementation. Additional studies are warranted in order to
      design adapted prescriptions in antioxidant vitamins and minerals.

PMID- 24323890
TI  - Activation of GPR119 by fatty acid agonists augments insulin release from clonal
      beta-cells and isolated pancreatic islets and improves glucose tolerance in mice.
AB  - G-protein coupled receptor 119 (GPR119) is emerging as a potential target for the
      treatment of type 2 diabetes with beneficial effects on glucose homeostasis. This
      study assessed the insulin-secreting properties of various GPR119 agonists and
      the distribution of GPR119 in pancreatic islets. Endogenous ligands
      [oleoylethanolamide (OEA), palmitoylethanolamine (PEA)] and chemically synthetic
      analogues (AS-1269574, PSN-375963) were investigated in clonal BRIN-BD11 cells
      and mouse pancreatic islets. Secondary messenger assays such as intracellular
      Ca2+ and cAMP in response to agonists at normoglycaemic and hyperglycaemic
      conditions were assessed. Cytotoxicity was assessed by LDH release. AS-1269574
      was the most potent and selective agonist tested in isolated islets, with an EC50
      value of 9.7*10-7 mol/l, enhancing insulin release maximally by 63.2%.
      Stimulation was also observed with GPR119 ligands; OEA (3.0*10-6 mol/l; 37.5%),
      PSN-375963 (2.4*10-6 mol/l; 28.7%) and PEA (1.2*10-6 mol/l; 22.2%). Results were
      corroborated by studies using BRIN-BD11 cells, which revealed augmentation of
      intracellular Ca2+ and cAMP. Both OEA and AS-1269574 enhanced insulin release and
      improved glucose tolerance in vivo in NIH Swiss mice. These results demonstrate
      the cellular localisation of GPR119 on islet cells (beta and pancreatic
      polypeptide cells), its activation of the beta-cell stimulus-secretion coupling
      pathway and glucose lowering effects in vivo.

PMID- 24323891
TI  - Analytical performance of a new one-step quantitative prostate-specific antigen
      assay, the FRENDTM PSA Plus.
AB  - BACKGROUND: We evaluated the analytical performance of a new one-step rapid
      quantitative sandwich immunoassay for total prostate-specific antigen (tPSA), the
      FRENDTM PSA Plus (FREND PSA) (NanoEnTek Inc., Seoul, Korea). METHODS: The
      imprecision, linearity, hook effect, detection limit (LoD), and interference were
      evaluated and trueness verification and matrix validation were performed. For
      method comparison, 79 patient specimens were analyzed with FREND PSA and two
      comparative tPSA assays (Architect(r) total PSA and cobas(r) total PSA assay).
      RESULTS: Total CVs of the imprecision for low (0.208 ng/mL), medium (4.051
      ng/mL), and high PSA levels (5.469 ng/mL) were 15.9%, 6.4%, and 9.1%,
      respectively. Linearity was observed from 1.01 to 19.15 ng/mL and the hook
      phenomenon was absent up to 171.48 ng/mL. The LoD was 0.094 ng/mL. The regression
      equations between FREND (y) and Architect or cobas were as follows:
      y=0.0133+1.054x (r=0.973), y=-0.2144+1.066x (r=0.977), respectively. Differences
      between FREND PSA and the comparative methods at a medical decision level of 4.0
      ng/mL were less than the optimum specification bias (9.3%). The percentage biases
      from the trueness verification and interference test were less than the desirable
      specifications for bias (18.7%). The plasma tPSA level measured with lithium
      heparin or K2EDTA was comparable to that in the serum. CONCLUSIONS: The FREND PSA
      provided reliable analytical performance and test results in comparison to two
      widely used tPSA assays. It is a simple and rapid test for tPSA and can be
      applied in point-of-care testing.

PMID- 24323892
TI  - Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic
      and non-diabetic patients.
AB  - BACKGROUND: Diabetes increases the risk and severity of atherosclerosis. Adropin,
      a metabolic homeostasis-related protein, has been implicated in the maintenance
      of metabolic homeostasis. We examined the relationship between serum adropin
      level and angiographic severity of coronary atherosclerosis in diabetic and non
      diabetic patients. METHODS: A total of 392 patients with suspected coronary
      artery disease, who underwent coronary angiography, were assigned into the type 2
      diabetic and non-diabetic groups and also classified into four groups according
      to the quartiles of adropin level. Venous serum samples were collected for
      adropin measurement by enzyme-linked immunosorbent assay and for biochemistry
      assay. The angiographic severity of coronary atherosclerosis was assessed by
      Gensini, Friesinger, and SYNTAX scores. RESULTS: Compared with non-diabetic
      patients, diabetic patients had lower serum adropin level and higher Gensini,
      Friesinger and SYNTAX scores (all p<0.001). Serum adropin level was inversely
      correlated with the Gensini, Friesinger and SYNTAX scores (rs=-0.389, -0.390 and 
      0.386, respectively, all p<0.001) among all patients. Low adropin level was an
      independent predictor of clinically relevant coronary atherosclerosis (SYNTAX
      score >11), both in diabetic patients [odds ratio (OR) 0.66, 95% confidence
      interval (CI) 0.53-0.83; p<0.001] and in non-diabetic patients (OR 0.51, 95% CI
      0.35-0.74; p<0.001). CONCLUSIONS: Serum adropin level was significantly lower in
      type 2 diabetic patients than in non-diabetic patients and was inversely and
      independently associated with angiographic severity of coronary atherosclerosis,
      suggesting that serum adropin serves as a novel predictor of coronary
      atherosclerosis.

PMID- 24323893
TI  - Semi-automatic selection of summary statistics for ABC model choice.
AB  - A central statistical goal is to choose between alternative explanatory models of
      data. In many modern applications, such as population genetics, it is not
      possible to apply standard methods based on evaluating the likelihood functions
      of the models, as these are numerically intractable. Approximate Bayesian
      computation (ABC) is a commonly used alternative for such situations. ABC
      simulates data x for many parameter values under each model, which is compared to
      the observed data x obs. More weight is placed on models under which S(x) is
      close to S(x obs), where S maps data to a vector of summary statistics. Previous
      work has shown the choice of S is crucial to the efficiency and accuracy of ABC.
      This paper provides a method to select good summary statistics for model choice.
      It uses a preliminary step, simulating many x values from all models and fitting
      regressions to this with the model as response. The resulting model weight
      estimators are used as S in an ABC analysis. Theoretical results are given to
      justify this as approximating low dimensional sufficient statistics. A
      substantive application is presented: choosing between competing coalescent
      models of demographic growth for Campylobacter jejuni in New Zealand using multi
      locus sequence typing data.

PMID- 24323895
TI  - Acri-2,7-Py, a bright red-emitting DNA probe identified through screening of a
      distyryl dye library.
AB  - The identification of DNA sensors is still a challenge since no DNA probe
      possesses all the photophysical properties required for live-cell imaging: high
      fluorescence yield, red emission, permeability, no photobleaching and no
      cytotoxicity. We describe the preparation of a distyryl dye library and its
      evaluation on a panel of nucleic acids with various structures (duplex DNA,
      quadruplex DNA and RNA). The screening involved measuring the modification of the
      fluorescence properties of the dyes with or without nucleic acids on a microplate
      reader, and allowed the identification of selective quadruplex DNA ligands with
      good affinities. Using this screening method we discovered a new bright red
      emitting DNA stain, Acri-2,7-Py, for fixed cells. In living cells, the staining
      was not nuclear and photodamage generated through illumination induced cellular
      death. These processes require further studies to determine the relevance of Acri
      2,7-Py in photodynamic therapy. 

PMID- 24323896
TI  - Study on an electrochromatography method based on organic-inorganic hybrid
      molecularly imprinted monolith for determination of trace trichlorfon in
      vegetables.
AB  - BACKGROUND: Organophosphorus pesticides have been widely used in agricultural
      production. However, the wide use of organophosphate also results in pesticide
      residues on the plant, which are harmful to human health because of their
      potential mutagenic and carcinogenic properties. Therefore, it is vital to
      develop a sensitive and effective analysis method to control pesticide residues.
      RESULTS: In this study, a novel molecularly imprinted capillary monolithic column
      was prepared using trichlorfon as the template molecule by combining non
      hydrolytic sol-gel process with a molecular imprinting technique. The resulting
      material was characterized by scanning electron microscopy and Fourier transform
      infrared. Under capillary electrochromatography, the effects of voltage, pH, ACN
      content and concentration of buffer solution on the electro-osmotic flow (EOF) of
      imprinted capillary monolithic column were evaluated in detail. Using this
      prepared material as stationary phase for capillary electrochromatography, a
      novel method of molecularly imprinted capillary electrochromatography (MICEC) for
      the detection of trace trichlorfon residues in vegetables was developed. Under
      optimal conditions, appreciable sensitivity was achieved with a LOD (S/N = 3) of
      92.5 ug kg(-1) and method quantitation limit (MQL) of 305.3 ug kg(-1),
      respectively. The linear ranges of the calibration graph were 0.1 ug L(-1) to 10
      mg L(-1). The peak area precision (RSD) for five replicate extractions of 0.01 mg
      L(-1) trichlorfon standard aqueous solution was 4.5%. To evaluate the accuracy of
      this method, the blank cucumber and cauliflower samples spiked with trichlorfon
      were extracted and analyzed by this method with good recoveries, ranging from
      80.2% to 95.8%. Moreover, this method was successfully applied to the
      quantitative detection of the trichlorfon residues in leek samples. CONCLUSION:
      With good properties of high sensitivity and simple pre-treatment, this MICEC
      method could provide a new tool for the rapid determination of trace trichlorfon
      residue in complex food samples.

PMID- 24323894
TI  - Substrates with patterned extracellular matrix and subcellular stiffness
      gradients reveal local biomechanical responses.
AB  - A substrate fabrication process is developed to pattern both the extracellular
      matrix (ECM) and rigidity at sub-cellular spatial resolution. When growing cells
      on these substrates, it is found that cells respond locally in their cytoskeleton
      assembly. The presented method allows unique insight into the biological
      interpretation of mechanical signals, whereas photolithography-based fabrication
      is amenable to integration with complex microfabricated substructures. 

PMID- 24323897
TI  - Assessment of a nonsteroidal aromatase inhibitor, letrozole, in juvenile rats.
AB  - BACKGROUND: The timing and duration of letrozole administration was designed to
      encompass the majority of postnatal development in the rat with the intent of
      evaluating the potential for a broad range of effects but with emphasis on
      expected effects on skeletal maturation. METHODS: Sprague-Dawley rats were
      administered letrozole via oral gavage at doses of 0.003, 0.03, and 0.3 mg/kg/day
      beginning on postpartum day (PPD) 7 through 91 followed by a 6-week recovery
      period. Clinical signs, body weight, food consumption, developmental endpoints,
      bone, ophthalmology, behavioral assessments, clinical/anatomic pathology,
      toxicokinetics, and reproductive assessments were conducted. RESULTS: Growth
      (body weight gain and crown-to-rump length) and food consumption were increased
      in females at >=0.03 mg/kg/day and decreased in males at >=0.003 mg/kg/day.
      Delayed sexual maturation in both sexes and adverse effects on reproductive
      function occurred at all doses. Effects on bone growth and maturation were noted
      in both sexes at all doses. Evidence of recovery was noted for males at 0.003
      mg/kg/day and females at 0.003 and 0.03 mg/kg/day upon withdrawal of treatment.
      Histopathological changes in the pituitary-adrenal-gonadal axis correlated with
      effects on reproductive function. CONCLUSIONS: The observed effects in juvenile
      rats were considered predictable and primarily related to the mechanism of action
      of letrozole upon estrogen synthesis.

PMID- 24323899
TI  - Myeloid-derived suppressor cells predict survival of patients with advanced
      melanoma: comparison with regulatory T cells and NY-ESO-1- or melan-A-specific T
      cells.
AB  - PURPOSE: To analyze the prognostic relevance and relative impact of circulating
      myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) compared
      with functional tumor antigen-specific T cells in patients with melanoma with
      distant metastasis. EXPERIMENTAL DESIGN: The percentage of CD14(+)CD11b(+)HLA-DR(
      /low) MDSCs, CD4(+)CD25(+)FoxP3(+) Tregs, and the presence of NY-ESO-1- or Melan
      A-specific T cells was analyzed in 94 patients and validated in an additional
      cohort of 39 patients by flow cytometry. Univariate survival differences were
      calculated according to Kaplan-Meier and log-rank tests. Multivariate analyses
      were performed using Cox regression models. RESULTS: NY-ESO-1-specific T cells,
      the M-category, and the frequency of MDSCs were associated with survival. The
      absence of NY-ESO-1-specific T cells and the M-category M1c independently
      increased the risk of death. In a second Cox model not considering results on
      antigen-specific T cells, a frequency of >11% MDSCs showed independent impact.
      Its association with survival was confirmed in the additional patient cohort.
      Median survival of patients with a lower frequency of MDSCs was 13 months versus
      8 months for others (P < 0.001, combined cohorts). We observed a strong
      correlation between high levels of MDSCs and the absence of melanoma antigen
      specific T cells implying a causal and clinically relevant interaction. No
      prognostic impact was observed for Tregs. CONCLUSIONS: Circulating
      CD14(+)CD11b(+)HLA-DR(-/low) MDSCs have a negative impact on survival and
      inversely correlate with the presence of functional antigen-specific T cells in
      patients with advanced melanoma. Our findings provide a rationale to investigate
      MDSC-depleting strategies in the therapeutic setting especially in combination
      with vaccination or T-cell transfer approaches.

PMID- 24323900
TI  - Molecular pathways: targeting the microenvironment in chronic lymphocytic
      leukemia--focus on the B-cell receptor.
AB  - Interactions between malignant B lymphocytes and the tissue microenvironment play
      a major role in the pathogenesis of chronic lymphocytic leukemia (CLL) and other
      B-cell malignancies. The coexistence and coevolution of CLL cells with their
      tissue neighbors provided the basis for discovery of critical cellular and
      molecular drivers of the disease and identification of new therapeutic targets.
      Bone marrow stromal cells (BMSC), monocyte-derived nurselike cells (NLC), and T
      cells are key players in the CLL microenvironment, which activate and protect CLL
      cells within the tissues. CLL surface molecules, such as the B-cell antigen
      receptor (BCR), chemokine receptors, adhesion molecules, and TNF receptor
      superfamily members (e.g., CD40, BCMA, and BAFF-R) engage in cross-talk with
      respective tissue ligands. This cross-talk results in survival and expansion of
      the CLL clone, and protects CLL cells from conventional cytotoxic drugs.
      Inhibiting these pathways represents an alternative therapeutic strategy to more
      conventional chemoimmunotherapy. Here, we review central components of the CLL
      microenvironment, with a particular emphasis on BCR signaling, and we summarize
      the most relevant clinical advances with inhibitors that target the BCR
      associated spleen tyrosine kinase/SYK (fostamatinib), Bruton's tyrosine
      kinase/BTK (ibrutinib), and PI3Kdelta (idelalisib).

PMID- 24323898
TI  - Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma.
AB  - PURPOSE: Small cell neuroendocrine carcinoma of the prostate is likely to become
      increasingly common with recent advances in pharmacologic androgen suppression.
      Thus, developing molecular markers of small cell differentiation in prostate
      cancer will be important to guide the diagnosis and therapy of this aggressive
      tumor. EXPERIMENTAL DESIGN: We examined the status of RB1, TP53, and PTEN in
      prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy
      number alteration analysis, and sequencing of formalin-fixed paraffin-embedded
      specimens. RESULTS: We found retinoblastoma (Rb) protein loss in 90% of small
      cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13).
      Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43%
      (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade
      acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with
      neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate
      resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN
      protein was seen in 63% of small cell carcinomas (17 of 27), with 38% (5 of 13)
      showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small
      cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation.
      CONCLUSIONS: Loss of RB1 by deletion is a common event in prostatic small cell
      carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely
      occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical
      event in the development of small cell carcinomas and may be a useful diagnostic
      and potential therapeutic target.

PMID- 24323902
TI  - Surveillance of the tumor mutanome by T cells during progression from primary to
      recurrent ovarian cancer.
AB  - PURPOSE: Cancers accumulate mutations over time, each of which brings the
      potential for recognition by the immune system. We evaluated T-cell recognition
      of the tumor mutanome in patients with ovarian cancer undergoing standard
      treatment. EXPERIMENTAL DESIGN: Tumor-associated T cells from 3 patients with
      ovarian cancer were assessed by ELISPOT for recognition of nonsynonymous
      mutations identified by whole exome sequencing of autologous tumor. The relative
      levels of mutations and responding T cells were monitored in serial tumor samples
      collected at primary surgery and first and second recurrence. RESULTS: The vast
      majority of mutations (78/79) were not recognized by tumor-associated T cells;
      however, a highly specific CD8(+) T-cell response to the mutation hydroxysteroid
      dehydrogenase-like protein 1 (HSDL1)(L25V) was detected in one patient. In the
      primary tumor, the HSDL1(L25V) mutation had low prevalence and expression, and a
      corresponding T-cell response was undetectable. At first recurrence, there was a
      striking increase in the abundance of the mutation and corresponding MHC class I
      epitope, and this was accompanied by the emergence of the HSDL1(L25V)-specific
      CD8(+) T-cell response. At second recurrence, the HSDL1(L25V) mutation and
      epitope continued to be expressed; however, the corresponding T-cell response was
      no longer detectable. CONCLUSION: The immune system can respond to the evolving
      ovarian cancer genome. However, the T-cell response detected here was rare, was
      transient, and ultimately failed to prevent disease progression. These findings
      reveal the limitations of spontaneous tumor immunity in the setting of standard
      treatments and suggest a high degree of ignorance of tumor mutations that could
      potentially be reversed by immunotherapy.

PMID- 24323901
TI  - Colon cancer cells escape 5FU chemotherapy-induced cell death by entering
      stemness and quiescence associated with the c-Yes/YAP axis.
AB  - PURPOSE: Metastasis and drug resistance are the major limitations in the survival
      and management of patients with cancer. This study aimed to identify the
      mechanisms underlying HT29 colon cancer cell chemoresistance acquired after
      sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for
      treatment of epithelial solid tumors. We examined its clinical relevance in a
      cohort of patients with colon cancer with liver metastases after 5FU-based
      neoadjuvant chemotherapy and surgery. RESULTS: We show that a clonal 5F31 cell
      population, resistant to 1 MUmol/L 5FU, express a typical cancer stem cell-like
      phenotype and enter into a reversible quiescent G0 state upon reexposure to
      higher 5FU concentrations. These quiescent cells overexpressed the tyrosine
      kinase c-Yes that became activated and membrane-associated upon 5FU exposure.
      This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes
      associated protein) molecular complex and depleted nuclear YAP levels.
      Consistently, YES1 silencing decreased nuclear YAP accumulation and induced
      cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1
      and YAP transcript levels were higher in liver metastases of patients with colon
      cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP
      transcript levels positively correlated with colon cancer relapse and shorter
      patient survival (P < 0.05 and P < 0.025, respectively). CONCLUSIONS: We
      identified c-Yes and YAP as potential molecular targets to eradicate quiescent
      cancer cells and dormant micrometastases during 5FU chemotherapy and resistance
      and as predictive survival markers for colon cancer.

PMID- 24323903
TI  - Adaptive prediction model in prospective molecular signature-based clinical
      studies.
AB  - Use of molecular profiles and clinical information can help predict which
      treatment would give the best outcome and survival for each individual patient,
      and thus guide optimal therapy, which offers great promise for the future of
      clinical trials and practice. High prediction accuracy is essential for selecting
      the best treatment plan. The gold standard for evaluating the prediction models
      is prospective clinical studies, in which patients are enrolled sequentially.
      However, there is no statistical method using this sequential feature to adapt
      the prediction model to the current patient cohort. In this article, we propose a
      reweighted random forest (RWRF) model, which updates the weight of each decision
      tree whenever additional patient information is available, to account for the
      potential heterogeneity between training and testing data. A simulation study and
      a lung cancer example are used to show that the proposed method can adapt the
      prediction model to current patients' characteristics, and, therefore, can
      improve prediction accuracy significantly. We also show that the proposed method
      can identify important and consistent predictive variables. Compared with
      rebuilding the prediction model, the RWRF updates a well-tested model gradually,
      and all of the adaptive procedure/parameters used in the RWRF model are
      prespecified before patient recruitment, which are important practical advantages
      for prospective clinical studies.

PMID- 24323904
TI  - Trabecular bone structure in the primate wrist.
AB  - Trabecular (or cancellous) bone has been shown to respond to mechanical loading
      throughout ontogeny and thus can provide unique insight into skeletal function
      and locomotion in comparative studies of living and fossil mammalian morphology.
      Trabecular bone of the hand may be particularly functionally informative because
      the hand has more direct contact with the substrate compared with the remainder
      of the forelimb during locomotion in quadrupedal mammals. This study investigates
      the trabecular structure within the wrist across a sample of haplorhine primates
      that vary in locomotor behaviour (and thus hand use) and body size. High
      resolution microtomographic scans were collected of the lunate, scaphoid, and
      capitate in 41 individuals and eight genera (Homo, Gorilla, Pan, Papio, Pongo,
      Symphalangus, Hylobates, and Ateles). We predicted that particular trabecular
      parameters would 1) vary across suspensory, quadrupedal, and bipedal primates
      based on differences in hand use and load, and 2) scale with carpal size
      following similar allometric patterns found previously in other skeletal elements
      across a larger sample of mammals and primates. Analyses of variance (trabecular
      parameters analysed separately) and principal component analyses (trabecular
      parameters analysed together) revealed no clear functional signal in the
      trabecular structure of any of the three wrist bones. Instead, there was a large
      degree of variation within suspensory and quadrupedal locomotor groups, as well
      as high intrageneric variation within some taxa, particularly Pongo and Gorilla.
      However, as predicted, Homo sapiens, which rarely use their hands for locomotion
      and weight support, were unique in showing lower relative bone volume (BV/TV)
      compared with all other taxa. Furthermore, parameters used to quantify trabecular
      structure within the wrist scale with size generally following similar allometric
      patterns found in trabeculae of other mammalian skeletal elements. We discuss the
      challenges associated with quantifying and interpreting trabecular bone within
      the wrist.

PMID- 24323905
TI  - Nanoneedle-assisted delivery of site-selective peptide-functionalized DNA
      nanocages for targeting mitochondria and nuclei.
AB  - Peptide-functionalized DNA nano-objects selectively target mitochondria and the
      nucleus by means of nanoneedle-assisted delivery. This technology preserves the
      cell viability and structural integrity of nanostructures and assists the nano
      objects in escaping degradation by endocytosis. This method opens up a new avenue
      for further in vitro studies of intracellular behaviors of DNA assemblies and
      their interactions in specific organelles. 

PMID- 24323906
TI  - Nonspecific hyper-reactivity and localized allergy: cause of discrepancy between
      skin prick and nasal provocation test.
AB  - OBJECTIVE: Disagreement between results of skin prick test (SPT) and nasal
      provocation tests (NPT) causes difficulty in differential diagnosis of allergic
      rhinitis (AR) and nonallergic rhinitis (NAR). We hypothesized this discrepancy
      could be due to the nonspecific hyper-reactivity (NHR) and localized allergy of
      the nasal cavity. STUDY DESIGN: Prospective pilot. SETTING: Academic tertiary
      rhinologic practice. SUBJECTS AND METHODS: Sixty patients with AR and 62 with NAR
      were enrolled. We categorized patients according to results of SPT and NPT. We
      compared: (1) the clinical characteristics and severity of the disease, (2)
      change of minimal cross-sectional area (MCA) and total nasal volume (TNV) after
      normal saline (NS) challenge, and (3) change of nasal symptoms and acoustic
      parameters after intranasal house dust mite (HDM) challenge between groups.
      RESULTS: Patients in groups A (SPT[+]/NPT[+]) and C (SPT[-]/NPT[+]) complained of
      more persistent discomfort than those in groups B (SPT[+]/NPT[-]) and D (SPT[
      ]/NPT[-]). The proportion of moderate to severe symptoms was significantly higher
      in groups A, B, and C compared to group D. After NS challenge, MCA/TNV showed a
      significantly greater decrease in groups A (MCA: 27.6% +/- 21.3%, TNV: 24.6% +/-
      16.4%) and C (MCA: 31.2% +/- 24.0%, TNV: 24.1% +/- 23.4%) compared to groups B
      (MCA: 0.1% +/- 13.2%, TNV: 3.9% +/- 13.5%) and D (MCA: 2.1% +/- 12.1%, TNV: 2.0%
      +/- 17.2%) (P < .05). After HDM challenge, groups A/B showed a greater decrease
      in MCA (Group A: 62.4% +/- 16.1%, Group B: 6.4% +/- 11.3%) compared to groups C/D
      (Group C: 45.5% +/- 14.4%, Group D: -3.0% +/- 9.5%). CONCLUSION: NHR and/or
      localized allergy should be considered in patients with rhinitis whose SPT and
      NPT results are not in agreement.

PMID- 24323907
TI  - Outcomes of combined Furlow palatoplasty and sphincter pharyngoplasty for
      velopharyngeal insufficiency.
AB  - OBJECTIVE: To compare surgical outcomes between pharyngeal flap, sphincter
      pharyngoplasty, and combined Furlow palatoplasty and sphincter pharyngoplasty in
      the management of pediatric velopharyngeal insufficiency. STUDY DESIGN: Case
      series with chart review. SETTING: Tertiary care pediatric hospital. SUBJECTS AND
      METHODS: After exclusion of children with velocardiofacial syndrome, 96 patients
      who underwent surgical intervention between 2008 and 2012 were identified.
      Surgical interventions were categorized as pharyngeal flap, sphincter
      pharyngoplasty, and combined Furlow palatoplasty and sphincter pharyngoplasty.
      Main outcome measures included perceptual speech analyses, complications, and
      surgical revision rates. RESULTS: Of the 96 reviewed patients, 38 (39.6%)
      underwent pharyngeal flap, 20 (20.8%) sphincter pharyngoplasty, and 38 (39.6%)
      combined Furlow palatoplasty and sphincter pharyngoplasty. Choice of surgical
      intervention was based on patient characteristics, observed palatal length, and
      formal speech assessments. There were no differences in patient demographics or
      preoperative perceptual speech analysis scores among the 3 surgical groups. The
      mean speech improvement was significantly greater in both the pharyngeal flap (P
      = .031) and combined procedure (P = .013) compared with sphincter pharyngoplasty
      alone, but no differences were observed between the pharyngeal flap and combined
      procedure (P = .797). There were no differences in complications among the 3
      surgical interventions (P = .220). The combined procedure required significantly
      less surgical revisions than the pharyngeal flap (P = .019). CONCLUSION: Combined
      Furlow palatoplasty and sphincter pharyngoplasty is an effective procedure for
      the management of pediatric velopharyngeal insufficiency and may result in
      superior speech outcomes and lower revision rates than sphincter pharyngoplasty
      and pharyngeal flap, respectively.

PMID- 24323908
TI  - Supraglottoplasty in premature infants with laryngomalacia: does gestation age at
      birth influence outcomes?
AB  - PURPOSE: Prematurity is thought to be to be an independent risk factor for
      supraglottoplasty (SGP) failure. The purpose of this study was to compare the
      outcomes of supraglottoplasty in premature infants with congenital laryngomalacia
      (LM) with that of term infants. STUDY DESIGN: Case series with chart review.
      SETTING: Tertiary-care pediatric institution. METHODS: Analysis was performed on
      325 consecutive patients undergoing SGP between 2004 and 2012. Patients older
      than 12 months age or with syndrome, neurologic, or cardiac comorbidities were
      excluded. Resolution of airway symptoms after SGP was considered successful while
      revision SGP and tracheostomy were considered failures. The rates of secondary
      airway lesions (SAL), dysphagia, and gastrostomy tube (GT) placement were also
      compared. RESULTS: A total of 176 infants (136 term, 40 preterm) were identified.
      SGP was successful in 92.7% term and 90% preterm infants with no significant
      difference (P = .5865). Incidence of revision SGP and tracheostomy was similar
      among the groups. The outcomes of SGP were the same in all groups stratified by
      age. Incidence of SAL was significantly higher in preterm (72.5%) compared to
      term infants (34.6%, P = .0002). Dysphagia rates in the follow-up were higher in
      preterm (32.5%) versus term infants (6.6%, P < .001). The rate of GT insertion
      was significantly greater (P = .003) in preterm (27.5%) than term infants (6.6%).
      The preoperative dysphagia, persistent dysphagia, and GT in follow-up was
      significantly higher when gestation age <32 weeks (25%, P = .0168). CONCLUSION:
      Supraglottoplasty outcomes in term and preterm infants were similar irrespective
      of gestation age. Higher rates of dysphagia in follow-up are seen when gestation
      age <32 weeks.

PMID- 24323909
TI  - Fluorescence visualization screening for EBV-LMP1-targeted DNAzymes.
AB  - OBJECTIVES: To develop a novel screening method for DNAzymes targeting the LMP1
      carboxy region. STUDY DESIGN: To design a method to screen special DNAzymes
      toward the Epstein-Barr virus (EBV)-associated carcinoma before clinic use.
      SETTING: Key Laboratory of the Ministry of Education-Molecular Biology of
      Infectious Diseases in Chongqing Medical University. SUBJECTS AND METHODS: Four
      novel 10-23 DNAzymes (DZ509, DZ1037, DZ893, and DZ827) targeting the EBV-LMP1
      gene were designed and evaluated by detecting enhanced green fluorescence protein
      (EGFP) expression of LMP1 mRNA and the protein in the nasopharyngeal carcinoma
      (NPC) cell line CNE2 transfected with the pEGFP-C1-LMP1c vector. The screened
      specific DNAzymes were then transfected into NPC cell lines C666-1 while a mutant
      oligonucleotide mutDZ509 and an antisense oligonucleotide ASODN509 were designed
      as positive and negative controls. Cell proliferation, cell apoptosis, LMP1 mRNA,
      and the protein were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assay, Annexin V-fluorescence isothiocyanate
      (FITC), reverse transcription polymerase chain reaction (RT-PCR), and Western
      blots. RESULTS: The inhibition rates of fluorescence expression of the DNAzymes
      DZ509, DZ1037, DZ893, and DZ827 were 91.25%, 65.84%, 49.02%, and 44.56%,
      respectively. The results were in accordance with the inhibition effects of mRNA
      and protein expression. The screened DZ509 could effectively knock down
      endogenous LMP1 expression in C666-1 cells, inhibit cell proliferation, and
      induce cell apoptosis compared with mutDZ509 and ASODN509. CONCLUSION: LMP1 could
      present a potential target for DNAzymes toward the EBV-associated carcinoma, and
      the EGFP expression vector could be a visible method for screening special
      DNAzymes before clinic use.

PMID- 24323910
TI  - Fatty acid metabolism, energy expenditure and insulin resistance in muscle.
AB  - Fatty acids (FAs) are essential elements of all cells and have significant roles
      as energy substrates, components of cellular structure and signalling molecules.
      The storage of excess energy intake as fat in adipose tissue is an evolutionary
      advantage aimed at protecting against starvation, but in much of today's world,
      humans are faced with an unlimited availability of food, and the excessive
      accumulation of fat is now a major risk for human health, especially the
      development of type 2 diabetes (T2D). Since the first recognition of the
      association between fat accumulation, reduced insulin action and increased risk
      of T2D, several mechanisms have been proposed to link excess FA availability to
      reduced insulin action, with some of them being competing or contradictory. This
      review summarises the evidence for these mechanisms in the context of excess
      dietary FAs generating insulin resistance in muscle, the major tissue involved in
      insulin-stimulated disposal of blood glucose. It also outlines potential problems
      with models and measurements that may hinder as well as help improve our
      understanding of the links between FAs and insulin action. 

PMID- 24323911
TI  - Role of sphingolipids in oestrogen signalling in breast cancer cells: an update.
AB  - The signaling pathways activated by the steroid hormone oestrogen include a
      variety of cytoplasmic second messengers linked to a multitude of tissue-specific
      effects. In the last decade, sphingolipids and their membrane receptors were
      added to the list of oestrogen-activated mediators. Oestrogen triggers the
      sphingolipid signalling cascade in various tissues including breast cancer.
      Extensive research has shown that sphingolipids are the key regulatory molecules
      in growth factor networks. Sphingolipids can control the rate of cell
      proliferation and the differentiation outcome during malignant transformation. In
      this study, we summarise novel experimental evidences linking sphingolipids to
      oestrogen-activated effects, highlight the role of sphingolipids in cancer cells
      and discuss new avenues for future research at the intersection between oestrogen
      and sphingolipid signalling. 

PMID- 24323912
TI  - Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS.
AB  - The delivery of nutrients to the gastrointestinal tract after food ingestion
      activates the secretion of several gut-derived mediators, including the incretin
      hormone glucagon-like peptide 1 (GLP-1). GLP-1 receptor agonists (GLP-1RA), such
      as exenatide and liraglutide, are currently employed successfully in the
      treatment of patients with type 2 diabetes mellitus. GLP-1RA improve glycaemic
      control and stimulate satiety, leading to reductions in food intake and body
      weight. Besides gastric distension and peripheral vagal nerve activation, GLP-1RA
      induce satiety by influencing brain regions involved in the regulation of
      feeding, and several routes of action have been proposed. This review summarises
      the evidence for a physiological role of GLP-1 in the central regulation of
      feeding behaviour and the different routes of action involved. Also, we provide
      an overview of presently available data on pharmacological stimulation of GLP-1
      pathways leading to alterations in CNS activity, reductions in food intake and
      weight loss. 

PMID- 24323913
TI  - Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress
      response in rats.
AB  - Bisphenol A (BPA) is an estrogen-mimicking endocrine disruptor. Early-life
      exposures to low doses of BPA exert long-lasting effects on animals' reproductive
      and brain physiology. However, little is known about the effects of BPA on the
      stress-response system. Given the interaction of sex and stress hormones, we
      examined the effect of a low perinatal BPA exposure on the function of the
      hypothalamic-pituitary-adrenal (HPA) axis at rest and upon application of acute
      stress. Throughout pregnancy and lactation rats received daily 40 MUg BPA/kg body
      weight orally via cornflakes. We studied the effect of this low but chronic
      exposure to BPA in the male and female offspring at puberty. BPA exposure led to
      abnormal adrenal histology including reduced zona reticularis especially in male
      offspring, hyperplasia of zona fasciculata in both sexes, and increased adrenal
      weight in female offspring. BPA-treated females had increased basal
      corticosterone and reduced hypothalamic glucocorticoid receptors (GR) levels.
      Stressed BPA-exposed females exhibited anxiety-like behavioral coping, a less
      rigorous corticosterone response, and did not downregulate GR in the
      hypothalamus, compared with control females. BPA-exposed males exhibited a
      heightened corticosterone stress response compared with females; they also
      displayed increased pro-opiomelanocortin mRNA levels and retained the prestress
      levels of pituitary corticotropin-releasing hormone-receptor 1, compared with
      control males. We found that perinatal chronic exposure to a low dose of BPA
      perturbs the basal and stress-induced activity of the HPA axis in a sexually
      dimorphic manner at adolescence. Exposure to BPA might contribute to increased
      susceptibility to stress-related disorders in later life. 

PMID- 24323914
TI  - Phytoestrogens for menopausal vasomotor symptoms.
AB  - BACKGROUND: Vasomotor symptoms, such as hot flushes and night sweats, are very
      common during the menopausal transition. Hormone therapy has traditionally been
      used as a highly effective treatment, but concerns about increased risk of some
      chronic diseases have markedly increased the interest of women in alternative
      treatments. Some of the most popular of these treatments are foods or supplements
      enriched with phytoestrogens-plant-derived chemicals that have estrogenic action.
      OBJECTIVES: To assess the efficacy, safety and acceptability of food products,
      extracts and dietary supplements containing high levels of phytoestrogens when
      compared with no treatment, placebo or hormone therapy for the amelioration of
      vasomotor menopausal symptoms (such as hot flushes and night sweats) in
      perimenopausal and postmenopausal women. SEARCH METHODS: Searches targeted the
      following electronic databases: the Cochrane Menstrual Disorders and Subfertility
      Group Specialised Register of randomised trials (29 July 2013), the Cochrane
      Register of Controlled Trials (CENTRAL; 29 July 2013), MEDLINE (inception to 29
      July 2013), EMBASE (inception to 29 July 2013), AMED (1985 to 29 July 2013),
      PsycINFO (inception to 29 July 2013) and CINAHL (inception to 29 July 2013).
      Attempts were made to access grey literature by sending letters to pharmaceutical
      companies and performing searches of ongoing trial registers. Reference lists of
      included trials were also searched. SELECTION CRITERIA: Studies were included if
      they were randomised, included perimenopausal or postmenopausal participants with
      vasomotor symptoms (hot flushes or night sweats), lasted at least 12 weeks and
      provided interventions such as foods or supplements with high levels of
      phytoestrogens (not combined with other herbal treatments). Trials that included
      women who had breast cancer or a history of breast cancer were excluded. DATA
      COLLECTION AND ANALYSIS: Selection of trials, extraction of data and assessment
      of quality were undertaken by at least two review authors. Most trials were too
      dissimilar for their results to be combined in a meta-analysis, so these findings
      are provided in narrative 'Summary of results' tables. Studies were grouped into
      broad categories: dietary soy, soy extracts, red clover extracts, genistein
      extracts and other types of phytoestrogens. Five trials used Promensil, a red
      clover extract; results of these trials were combined in a meta-analysis, and
      summary effect measures were calculated. MAIN RESULTS: A total of 43 randomised
      controlled trials (4,364 participants) were included in this review. Very few
      trials provided data suitable for inclusion in a meta-analysis. Among the five
      trials that yielded data assessing the daily frequency of hot flushes suitable
      for pooling, no significant difference overall was noted in the incidence of hot
      flushes between participants taking Promensil (a red clover extract) and those
      given placebo (mean difference (MD) -0.93, 95% confidence interval (CI) -1.95 to
      0.10, I(2) = 31%). No evidence indicated a difference in percentage reduction in
      hot flushes in two trials between Promensil and placebo (MD 20.15, 95% CI -12.08
      to 52.38, I(2) = 82%). Four trials that were not combined in meta-analyses
      suggested that extracts with high (> 30 mg/d) levels of genistein consistently
      reduced the frequency of hot flushes. Individual results from the remaining
      trials were compared in broad subgroups such as dietary soy, soy extracts and
      other types of phytoestrogens that could not be combined. Some of these trials
      found that phytoestrogen treatments alleviated the frequency and severity of hot
      flushes and night sweats when compared with placebo, but many trials were small
      and were determined to be at high risk of bias. A strong placebo effect was noted
      in most trials, with a reduction in frequency ranging from 1% to 59% with
      placebo. No indication suggested that discrepant results were due to the amount
      of isoflavone in the active treatment arm, the severity of vasomotor symptoms or
      trial quality factors. Also, no evidence indicated that these treatments caused
      oestrogenic stimulation of the endometrium or the vagina or other adverse effects
      when used for up to two years. AUTHORS' CONCLUSIONS: No conclusive evidence shows
      that phytoestrogen supplements effectively reduce the frequency or severity of
      hot flushes and night sweats in perimenopausal or postmenopausal women, although
      benefits derived from concentrates of genistein should be further investigated.

PMID- 24323915
TI  - When correlation and causation coincide.

PMID- 24323916
TI  - On the fundamental importance of non-linear responses.

PMID- 24323917
TI  - Bacterial genes in eukaryotes: relatively rare but real and important (Comment on
      DOI 10.1002/bies.201300095).

PMID- 24323918
TI  - Horizontal gene acquisitions by eukaryotes as drivers of adaptive evolution.
AB  - In contrast to vertical gene transfer from parent to offspring, horizontal (or
      lateral) gene transfer moves genetic information between different species.
      Bacteria and archaea often adapt through horizontal gene transfer. Recent
      analyses indicate that eukaryotic genomes, too, have acquired numerous genes via
      horizontal transfer from prokaryotes and other lineages. Based on this we raise
      the hypothesis that horizontally acquired genes may have contributed more to
      adaptive evolution of eukaryotes than previously assumed. Current candidate sets
      of horizontally acquired eukaryotic genes may just be the tip of an iceberg. We
      have recently shown that adaptation of the thermoacidophilic red alga Galdieria
      sulphuraria to its hot, acid, toxic-metal laden, volcanic environment was
      facilitated by the acquisition of numerous genes from extremophile bacteria and
      archaea. Other recently published examples of horizontal acquisitions involved in
      adaptation include ice-binding proteins in marine algae, enzymes for carotenoid
      biosynthesis in aphids, and genes involved in fungal metabolism. Editor's
      suggested further reading in BioEssays Jumping the fine LINE between species:
      Horizontal transfer of transposable elements in animals catalyses genome
      evolution Abstract. 

PMID- 24323919
TI  - Exploiting CRISPR/Cas systems for biotechnology.
AB  - The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system,
      a prokaryotic adaptive restriction system against invading nucleic acids, such as
      those originating from bacteriophages and plasmids. Recently, this RNA-directed
      DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we
      review the development of Cas9 as an important tool to not only edit the genomes
      of a number of different prokaryotic and eukaryotic species, but also as an
      efficient system for site-specific transcriptional repression or activation.
      Additionally, a specific Cas9 protein has been observed to target an RNA
      substrate, suggesting that Cas9 may have the ability to be programmed to target
      RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in
      this regard. Thus, CRISPR/Cas systems represent an effective and versatile
      biotechnological tool, which will have significant impact on future advancements
      in genome engineering. 

PMID- 24323920
TI  - How do I kill thee? Let me count the ways: p53 regulates PARP-1 dependent
      necrosis.
AB  - Understanding the impact of the p53 tumor suppressor pathway on the regulation of
      genome integrity, cancer development, and cancer treatment has intrigued
      scientists and clinicians for decades. It appears that the p53 pathway is a
      central node for nearly all cell stress responses, including: gene expression,
      DNA repair, cell cycle arrest, metabolic adjustments, apoptosis, and senescence.
      In the past decade, it has become increasingly clear that p53 function is
      directly regulated by poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme
      involved in DNA repair signaling. Here, we will discuss the impact of PARP-1 on
      p53 function, along with a recently described novel role for the reciprocal
      regulation of p53 regulated, PARP-1 dependent necrosis following DNA damage. 

PMID- 24323921
TI  - Phosphatidylinositol 3,5-bisphosphate: low abundance, high significance.
AB  - Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5
      bisphosphate (PI(3,5)P2 ), reveal an intriguingly diverse list of downstream
      pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as
      links to neurodegenerative diseases. Derived from the structural lipid
      phosphatidylinositol, PI(3,5)P2 is dynamically generated on multiple cellular
      compartments where interactions with an increasing list of effectors regulate
      many cellular pathways. A complex of proteins that includes Fab1/PIKfyve, Vac14,
      and Fig4/Sac3 mediates the biosynthesis of PI(3,5)P2 , and mutations that disrupt
      complex function and/or formation cause profound consequences in cells.
      Surprisingly, mutations in this pathway are linked with neurological diseases,
      including Charcot-Marie-Tooth syndrome and amyotrophic lateral sclerosis. Future
      studies of PI(3,5)P2 and PI5P are likely to expand the roles of these lipids in
      regulation of cellular functions, as well as provide new approaches for treatment
      of some neurological diseases. 

PMID- 24323922
TI  - The photochemical determinants of color vision: revealing how opsins tune their
      chromophore's absorption wavelength.
AB  - The evolution of a variety of important chromophore-dependent biological
      processes, including microbial light sensing and mammalian color vision, relies
      on protein modifications that alter the spectral characteristics of a bound
      chromophore. Three different color opsins share the same chromophore, but have
      three distinct absorptions that together cover the entire visible spectrum,
      giving rise to trichromatic vision. The influence of opsins on the absorbance of
      the chromophore has been studied through methods such as model compounds, opsin
      mutagenesis, and computational modeling. The recent development of rhodopsin
      mimic that uses small soluble proteins to recapitulate the binding and wavelength
      tuning of the native opsins provides a new platform for studying protein
      regulated spectral tuning. The ability to achieve far-red shifted absorption in
      the rhodopsin mimic system was attributed to a combination of the lack of a
      counteranion proximal to the iminium, and a uniformly neutral electrostatic
      environment surrounding the chromophore. 

PMID- 24323923
TI  - One hundred years of somatic mutation theory of carcinogenesis: is it time to
      switch?

PMID- 24323928
TI  - The "true" affinities of metal cations to p-sulfonatocalix[4]arene: a
      thermodynamic study at neutral pH reveals a pitfall due to salt effects in
      microcalorimetry.
AB  - A microcalorimetric study on the inclusion of monovalent and divalent metal
      cations by p-sulfonatocalix[4]arene was performed. The thermodynamic parameters
      for the complexation of alkali metal cations and Ag(+) were obtained for the
      first time at neutral pH. The Na(+) cation is routinely present as counterion of
      the calixarene in neutral aqueous solution, and this must be taken into account
      in the determination of the thermodynamic parameters for the complexation of
      Na(+) and the other cations by considering a sequential or a competitive binding
      scheme. The DeltaH degrees  and DeltaS degrees  values show that the inclusion
      process is entropically driven, although an influence of the temperature on the
      complexation reaction indicates that the enthalpic term is also an important
      contributor. The results also reveal that enthalpy/entropy compensation balances
      the gain in one contribution against a corresponding loss in the other. The
      obtained thermodynamic data are in contrast to the results from previous
      microcalorimetric studies, which showed binding constants that were orders of
      magnitude smaller and complexations, which were in part enthalpically driven but
      which neglected the influence of the alkali metal counterions. 

PMID- 24323927
TI  - Regulation of renal function and structure by the signaling Na/K-ATPase.
AB  - The Na/K-ATPase as an essential ion pump was discovered more than 50 years ago
      (Skou (1989) Biochim. Biophys. Acta 1000, 439-446; Feraille and Doucet (2001)
      Physiol. Rev. 81, 345-418). The signaling function of Na/K-ATPase has been
      gradually appreciated over the last 20 years, first from the studies of
      regulatory effects of ouabain on cardiac cell growth. Several reviews on this
      topic have been written during the last few years (Schoner and Scheiner-Bobis
      (2007) Am. J. Physiol. Cell. Physiol. 293, C509-C536; Xie and Cai (2003) Mol.
      Interv. 3, 157 - 168; Bagrov et al. (2009) Pharmacol. Rev. 61, 9-38; Tian and Xie
      (2008) Physiology 23, 205-211; Fontana et al. (2013) FEBS J. 280, 5450-5455;
      Blanco and Wallace (2013) Am. J. Physiol. Renal Physiol. 305, F797-F812). This
      article will focus on the molecular mechanism of Na/K-ATPase-mediated signal
      transduction and its potential regulatory role in renal physiology and diseases.

PMID- 24323930
TI  - [Deposition and clearance of beta-amyloid in the brain].
AB  - Amyloid beta-protein (Abeta) is deposited as senile plaques and vascular amyloid
      in the brain of patients with Alzheimer's disease as well as in a significant
      proportion of non-demented elderly individuals. Microglia play critical roles in
      the uptake and proteolytic clearance of both the soluble and fibrillary forms of
      Abeta. Astrocytes separate fibrillary Abeta from neurons by extending
      hypertrophic processes and internalizing the Abeta into endosomes/lysosomes,
      suggesting their role in the degradation of Abeta. Recent studies have shown that
      perivascular clearance of Abeta is a two-step process, involving (i) the uptake
      of Abeta by glia limitans astrocytes and (ii) perivascular or transendothelial
      clearance after their secretion into the perivascular space.

PMID- 24323929
TI  - Endogenous microRNA clusters outperform chimeric sequence clusters in Chinese
      hamster ovary cells.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs (~22 nucleotides) which regulate
      gene expression by silencing mRNA translation. MiRNAs are transcribed as long
      primary transcripts, which are enzymatically processed by Drosha/Dgcr8, in the
      nucleus, and by Dicer in the cytoplasm, into mature miRNAs. The importance of
      miRNAs for coordinated gene expression is commonly accepted. Consequentially,
      there is a growing interest in the application of miRNAs to improve phenotypes of
      mammalian cell factories such as Chinese hamster ovary (CHO) cells. Few studies
      have reported the targeted over-expression of miRNAs in CHO cells using vector
      based systems. These approaches were hampered by limited sequence availability,
      and required the design of "chimeric" miRNA genes, consisting of the mature CHO
      miRNA sequence encompassed by murine flanking and loop sequences. Here we show
      that the substitution of chimeric sequences with CHO-specific sequences for
      expression of miRNA clusters yields significantly higher expression levels of the
      mature miRNA in the case of miR-221/222 and miR-15b/16. Our data suggest that the
      Drosha/Dgcr8-mediated excision from primary transcripts is reduced for chimeric
      miRNA sequences compared to the endogenous sequence. Overall, this study provides
      important guidelines for the targeted over-expression of clustered miRNAs in CHO
      cells. See accompanying commentary by Baik and Lee DOI: 10.1002/biot.201300503. 

PMID- 24323931
TI  - [Neuropathology of tauopathy].
AB  - Microtubules are key cytoskeletal elements found in all eukaryotic cells. Tau was
      identified as microtubule associated protein and was implicated in microtubule
      initiation as well as assembly. Its expression is increased expression in neurons
      and has a specific association with axonal microtubules. Neurodegenerative
      disorders associated with abundant tau inclusions are collectively described as
      tauopathies. Pathological inclusions in neurons and glial cells containing
      fibrillary aggregates of abnormally hyperphosphorylated tau protein are
      characteristic features of tauopathies. We outlined the pathological features of
      major tauopathies, including neurofibrillary tangle formation diseases, Pick's
      disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration
      (CBD), and argyrophilic grain disease (AGD). Disease specific isoform
      compositions of tau are identified in these tauopathies. Neurofibrillary tangles
      (NFTs) in Alzheimer's disease contain both three repeat (3R)- and four repeat
      (4R)-tau. Pick bodies in PiD are immunopositive for 3R-tau. In PSP NFTs, tufted
      astrocytes, coiled bodies and threads contain 4R-tau and in CBD, pretangles,
      astrocytic plaques, coiled bodies and threads also demonstrate 4R-tau.
      Argyrophilic grains are immunopositive for 4R-tau. Although PSP and CBD sometimes
      share certain pathological distribution, which makes clinical diagnosis
      difficult, cellular tau pathology and aggregation patterns in neurons and glia
      are different between the two diseases.

PMID- 24323932
TI  - [Hyperbranching axons template alpha-synuclein deposits and non-localizing
      clinical manifestations of Parkinson disease].
AB  - The "proteinopathy" hypothesis, which states that pathological inclusions result
      in neuronal death, is classically invoked to explain neurodegeneration. In this
      review on alpha-synuclein (alphaS), attention is shifted to the distal axons,
      where alphaS deposits earlier than in the cytoplasmic formation of Lewy bodies
      (LBs). Because LBs are preferentially formed in axons with abundant branching,
      hyperbranching may accentuate axonal degeneration and alphaS deposition in their
      distal ends. This hyperbranching may also explain why motor/non-motor symptoms of
      Parkinson disease (PD) are so generalized and diffuse with barely any localizing
      value. Such underlying structure templates both the distal-dominant degeneration
      with alphaS deposition, and the non-localizing nature of clinical manifestations
      of PD, and as such can be considered a "structural template" thereof. The
      evolution of PD symptoms can be highly variable, ranging from restricted LB
      lesions and corresponding, long-lived, symptoms (pure autonomic failure, cardiac
      denervation, essential tremor, and REM-related behavioral disorders, which may be
      collectively called "focal LB disease") to the more haphazard appearance of
      dementia or anosmia without developing parkinsonism or brainstem lesions. This
      variability is better explained by the parallel involvement of multiple systems
      with hyperbranching axons rather than the stereotyped upward spread of LB in the
      brainstem. Awareness of presynaptic dysfunctions of these hyperbranching systems
      may enhance the sensitivity and specificity of clinical diagnoses of PD for
      earlier therapeutic intervention.

PMID- 24323933
TI  - [Neuropathology of TDP-43 proteinopathy].
AB  - TAR DNA-binding protein 43 (TDP-43) is a member of the heterogeneous nuclear
      ribonucleoprotein family, a group of proteins involved in pre-mRNA splicing, RNA
      stability, transport, and metabolism. TDP-43 was identified as the major
      component of pathological protein aggregates present in a subset of
      frontotemporal lobar degeneration (FTLD), which is now referred to as FTLD-TDP.
      TDP-43 is also deposited in the sporadic form of amyotrophic lateral sclerosis
      (ALS) as well as in familial ALS with mutations in the gene for TDP-43. Based on
      histopathology, the accumulation of TDP-43 in the brain cortex is classified into
      4 types, type A through D, depending on the forms of TDP-43 accumulation in the
      cerebral cortex. Type A pathology is frequently observed in frontotemporal
      dementia and progressive non-fluent aphasia. Type B pathology occurs in FTLD with
      ALS and ALS with lesions that extend to the cerebral cortex. Type C pathology is
      associated with semantic dementia. In FTLD and ALS, TDP-43 forms insoluble
      aggregates and gets phosphorylated, ubiquitinated, and fragmented. The fragment
      patterns on immunoblot of brain homogenates correspond to each histopathological
      type, indicating their relevance to the pathogenesis of TDP-43 proteinopathy.

PMID- 24323934
TI  - [Roles of metabolic compartmentalization by astrocytes and neurons in the
      pathophysiology and treatment of Parkinson's disease].
AB  - Mitochondrial dysfunction has been implicated in the pathogenesis of both
      idiopathic and familial Parkinson's disease (PD). Dopamine neurons in the
      substantia nigra exhibit autonomous pacemaking activity to maintain an optimal
      dopamine concentration in the striatum, resulting in the activation of energy
      metabolism. ATP production in neuronal cells is dependent on mitochondrial
      glucose oxidation, and reactive oxygen species (ROS) production associated with
      neuronal activation might be a major cause of mitochondrial damage in dopamine
      neurons. Alpha-synuclein, a major component of Lewy bodies, induces mitochondrial
      damage, and several genes responsible for familial PD encode molecules necessary
      for normal mitochondrial function. In addition, the auto-oxidation of dopamine
      produces dopamine quoinone and ROS. Astroglia provide neurons with lactate
      produced from glucose via glycolysis in response to neuronal activation. The co
      activation of the pentose-phosphate pathway (PPP), a shunt pathway of glycolysis,
      in astroglia plays a pivotal role in protecting neurons against ROS with
      glutathione peroxidase and the reduced form of glutathione (GSH). In addition to
      the allosteric regulation of the PPP, which is associated with the activation of
      glycolysis, the PPP in astroglia can also be activated by ROS through the Kelch
      like enoyl-CoA hydratase-associated protein 1 (Keap1)/nuclear factor-erythroid 2
      p45 subunit-related factor 2 (Nrf2) system. A rate-limiting enzyme of the PPP,
      glucose-6-phosphate dehydrogenase (G6PDH), is transcriptionally regulated by the
      Keap1/Nrf2 system, which is a master regulator of phase 2 detoxifying enzymes.
      ROS is thought to modify the thiol residue of Keap1 and to facilitate Nrf2
      dissociation from Keap1. Thereafter, Nrf2 translocates into the nucleus where it
      induces the transcription of G6PDH. The pharmacological activation of the
      Keap1/Nrf2 PPP in astroglia may provide a novel strategy for preventing the onset
      and progression of PD.

PMID- 24323935
TI  - [A case of spectacular shrinking deficit caused by paradoxical cerebral embolism
      secondary to pulmonary arteriovenous fistula].
AB  - We report a case of spectacular shrinking deficit caused by paradoxical cerebral
      embolism through pulmonary arteriovenous fistula (AVF). A 79-year-old female
      suddenly developed right hemiplegia, paresthesia, and speech disturbance symptoms
      that were improved within 20 min, indicating a diagnosis of spectacular shrinking
      deficit. Brain magnetic resonance imaging revealed acute cerebral infarcts in the
      left parietal cortex of the left middle cerebral arterial territory. A contrast
      enhanced chest computed tomography scan revealed a pulmonary AVF in the middle
      lobe of the right lung. The patient had deep venous thrombosis in her left lower
      leg. She had no clinical signs of telangiectasia, did not exhibit recurrent
      epistaxis, and had no family history of hereditary hemorrhagic telangiectasia
      (HHT). Therefore, she was diagnosed with paradoxical cerebral embolism secondary
      to the pulmonary AVF without HHT. Pulmonary AVF should be considered in patients
      with cerebral embolism, even when presenting with spectacular shrinking deficit.

PMID- 24323936
TI  - [Stepwise improvement of visual field after preoperative embolization and tumor
      resection of cerebral metastasis of alveolar soft part sarcoma].
AB  - We report a patient with a brain metastasis from an alveolar soft part sarcoma
      (ASPS) of the thigh whose visual field defect was resolved in a stepwise manner
      after preoperative embolization and tumor resection. A 29-year-old man who had
      undergone surgery to remove an ASPS situated in the thigh developed headaches and
      homonymous hemianopsia. His visual field defect was evaluated using a Goldmann
      perimeter. He was found to have a large, well-circumscribed mass in the right
      occipital lobe. This mass was visible on brain computed tomography and magnetic
      resonance imaging and was strongly and homogeneously enhanced following contrast
      administration. Selective angiography revealed a hypervascular mass supplied by
      branches of the right middle cerebral artery, and preoperative particulate
      embolization was performed to reduce intraoperative bleeding. A tumor-supplying
      branch of the middle cerebral artery was superselectively catheterized. For
      embolization, polyvinyl alcohol (PVA) particles of 90-180 MUm in diameter were
      used. The visual field defect partially improved soon after the preoperative
      embolization. Surgical resection was performed 3 days after embolization, and the
      tumor was completely excised by a right occipital craniotomy. Preoperative
      embolization made the surgical resection easier. Intraoperative bleeding was
      easily controlled. The pathological diagnosis was ASPS. The intratumoral
      embolized vessels were filled with PVA particles. After resection, the patient
      progressed well with further improvement in visual field function. Rapid
      improvement of the visual field can be used as an indicator of successful
      embolization without complications. (Received: July 16, 2013, Accepted: September
      5, 2013).

PMID- 24323937
TI  - Nitrogen fertilisation increases biogenic amines and amino acid concentrations in
      Vitis vinifera var. Riesling musts and wines.
AB  - BACKGROUND: Wines rich in biogenic amines can cause adverse health effects to the
      consumer. Being nitrogen-containing substances, the amount of amines in wines
      might be strongly influenced by the rate of nitrogen fertiliser application
      during grape production. The aim of this work was to evaluate the effect of
      nitrogen fertilisation in the vineyard on the formation of biogenic amines in
      musts and wines. RESULTS: In a field experiment which compared unfertilised and
      fertilised (60 and 150 kg N ha(-1)) vines over two separate years, the total
      amine concentrations in must and wine increased. The latter was due to an
      increase of individual amines such as ethylamine, histamine, isopentylamine,
      phenylethylamine and spermidine in the musts and wines with the nitrogen
      application. Furthermore, the fermentation process increased the concentration of
      histamine and ethylamine in most of the treatments, while spermidine, spermine
      and isopentylamine concentrations generally decreased. Throughout both vintages,
      the concentrations of tyramine and histamine of the investigated musts and wines
      never reached detrimental levels to the health of non-allergenic people.
      CONCLUSIONS: Nitrogen fertilisation has a significant effect on amines formation
      in musts and wines. Furthermore, during fermentation, ethylamine and histamine
      increased while other amines were presumably serving as N sources during
      fermentation.

PMID- 24323939
TI  - Effects of melamine and cyanuric acid on embryo-fetal development in rats.
AB  - After the outbreak of acute renal failure associated with melamine-contaminated
      pet food, melamine and melamine-related compounds have become of great interest
      from a toxicologic perspective. We investigated the potential effects of melamine
      in combination with cyanuric acid (M + CA, 1:1) on pregnant dams and embryo-fetal
      development in rats. M + CA was orally administered to pregnant rats from
      gestational days 6 through 19 at doses of 0, 3, 10, and 30 mg/kg/day of both
      melamine and cyanuric acid. Maternal toxicity of rats administered 30 mg/kg/day M
      + CA was manifested as increased incidences of clinical signs and death; gross
      pathologic findings; higher blood urea nitrogen and creatinine levels; lower body
      weight gain and food intake; decreased thymus weight; and increased heart, lung,
      and kidney weights. Histopathological examinations revealed an increase in the
      incidence of congestion, tubular necrosis/degeneration, crystals, casts,
      mineralization, inflammatory cells in tubules, tubular dilation, and atrophy of
      glomeruli in maternal kidneys, whereas fetal kidneys did not show any
      histopathological changes. Developmental toxicity included a decrease in fetal
      (28%) and placental weights and a delay in fetal ossification (n = 7). Increased
      incidence of gross and histopathological changes in the maternal kidney was also
      found in the middle dose group (n = 12). No treatment-related maternal or
      developmental effects were observed in the low dose group (n = 12). Under these
      experimental conditions, M + CA is embryotoxic at an overt maternotoxic dose in
      rats and the no-observed-adverse-effect level of M + CA is considered to be 3
      mg/kg/day for pregnant dams and 10 mg/kg/day for embryo-fetal development. 

PMID- 24323940
TI  - All-oxide Raman-active traps for light and matter: probing redox homeostasis
      model reactions in aqueous environment.
AB  - Core-shell colloidal crystals can act as very efficient traps for light and
      analytes. Here it is shown that Raman-active probes can be achieved using SiO2
      TiO2 core-shell beads. These systems are successfully tested in monitoring of
      glutathione redox cycle at physiological concentration in aqueous environment,
      without need of any interfering enhancers. These materials represent a promising
      alternative to conventional, metal-based SERS probes for investigating chemical
      and biochemical reactions under real working conditions.

PMID- 24323941
TI  - The worm has turned: unexpected similarities between the transcription of
      enhancers and promoters in the worm and mammalian genomes.
AB  - Our understanding of biological processes in humans is often based on examination
      of analogous processes in other organisms. The nematode worm Caenorhabditis
      elegans has been a particularly valuable model, leading to Nobel prize winning
      discoveries in development and genetics. Until recently, however, the worm has
      not been widely used as a model to study transcription due to the lack of a
      comprehensive catalogue of its RNA transcripts. A recent study by Chen et al.
      uses next-generation sequencing to address this issue, mapping the transcription
      initiation sites in C. elegans and finding many unexpected similarities between
      the transcription of enhancers and promoters in the worm and mammalian genomes.
      As well as providing a valuable resource for researchers in the C. elegans
      community, these findings raise the possibility of using the worm as a model to
      investigate some key, current questions about transcriptional regulation that
      remain technically challenging in more complex organisms. 

PMID- 24323938
TI  - Functional assays for analysis of variants of uncertain significance in BRCA2.
AB  - Missense variants in the BRCA2 gene are routinely detected during clinical
      screening for pathogenic mutations in patients with a family history of breast
      and ovarian cancer. These subtle changes frequently remain of unknown clinical
      significance because of the lack of genetic information that may help establish a
      direct correlation with cancer predisposition. Therefore, alternative ways of
      predicting the pathogenicity of these variants are urgently needed. Since BRCA2
      is a protein involved in important cellular mechanisms such as DNA repair,
      replication, and cell cycle control, functional assays have been developed that
      exploit these cellular activities to explore the impact of the variants on
      protein function. In this review, we summarize assays developed and currently
      utilized for studying missense variants in BRCA2. We specifically depict details
      of each assay, including variants of uncertain significance analyzed, and
      describe a validation set of (genetically) proven pathogenic and neutral missense
      variants to serve as a golden standard for the validation of each assay.
      Guidelines are proposed to enable implementation of laboratory-based methods to
      assess the impact of the variant on cancer risk. 

PMID- 24323942
TI  - The double life of KLF5: Opposing roles in regulation of gene-expression,
      cellular function, and transformation.
AB  - The mechanisms by which cells control their growth and behavioral identities are
      complex and require adaptability to environmental changes. Transcription factors
      act as master controllers of many of these pivotal points through their ability
      to influence the expression of many thousands of downstream genes, and
      increasingly research is showing that transcription factor regulation of target
      genes can change in response to environmental stimuli and cell type such that
      their function is not prescribed but rather context-dependent. Kruppel like
      factor 5 (KLF5) is an example of such a transcription factor, where evidence of
      disparate effects on cell growth and differentiation in normal and transformed
      tissue are clear. Here we present and discuss the literature covering the
      differential roles of KLF5 in particular tissues and cancer states, and the
      mechanisms by which these differences are effected through the regulation of KLF5
      protein function in response to different cellular states and the direct effect
      on target gene expression.

PMID- 24323943
TI  - Suspension and optical properties of the crystalline lens in the eyes of basal
      vertebrates.
AB  - We have investigated the apparatus suspending the crystalline lens in the eyes of
      basal vertebrates. Data are presented for Holocephali (Chondrichthyes) and the
      actinopterygians Polypteriformes, Polyodontidae (Acipenseriformes),
      Lepisosteiformes, Amiiformes, and one teleost species, the banded archerfish
      (Toxotes jaculatrix). We also studied the optical properties of the lens in
      Polypteriformes, Lepisosteiformes, and the archerfish. Together with previously
      published results, our findings show that there are three basic types of lens
      suspension in vertebrates. These are i) a rotationally symmetric suspension
      (Petromyzontida, lampreys; Ceratodontiformes, lungfishes; Tetrapoda), ii) a
      suspension with a dorso-ventral axis of symmetry and a ventral papilla (all
      Chondrichthyes and Acipenseriformes), and iii) an asymmetric suspension with a
      ventral muscle and a varying number of ligaments (all Actinopterygii except for
      Acipenseriformes). Large eyes with presumably high spatial resolution have
      evolved in all groups. Multifocal lenses creating well-focused color images are
      also present in all groups studied. Stable and exact positioning of the lens, in
      many cases in combination with accommodative changes in lens position or shape,
      is achieved by all three types of lens suspension. It is somewhat surprising that
      lens suspensions are strikingly similar in Chondrichthyes and Acipenseriformes
      (Actinopterygii), while the suspension apparatus in Polypteriformes, usually
      being regarded as an actinopterygian group more basal than Acipenseriformes, are
      considerably more teleostean-like. This study completes a series of
      investigations on lens suspensions in nontetrapod vertebrates, covering all major
      groups except for the rare and highly derived coelacanths.

PMID- 24323944
TI  - Scaling up of physical activity interventions in Brazil: how partnerships and
      research evidence contributed to policy action.
AB  - The global health burden due to physical inactivity is enormous and growing.
      There is a need to consider new ways of generating evidence and to identify the
      role of government in promoting physical activity at the population level. In
      this paper, we summarize key findings from a large-scale cross-national
      collaboration to understand physical activity promotion in Brazil. We describe
      the main aspects of the partnership of Project GUIA (Guide for Useful
      Interventions for Activity in Brazil and Latin America) that sustained the
      collaborative effort for eight years and describe how the evidence gathered from
      the collaboration triggered political action in Brazil to scale up a physical
      activity intervention at the national level. Project GUIA is a cross-national
      multidisciplinary research partnership designed to understand and evaluate
      current efforts for physical activity promotion at the community level in Latin
      America. This example of scaling up is unprecedented for promoting health in the
      region and is an example that must be followed and evaluated.

PMID- 24323946
TI  - Ammonia-borane dehydrogenation by means of an unexpected pentacoordinate boron
      species: insights from density functional and molecular dynamics studies.

PMID- 24323945
TI  - Cellular and molecular mechanisms underlying blood vessel lumen formation.
AB  - The establishment of a functional vascular system requires multiple complex steps
      throughout embryogenesis, from endothelial cell (EC) specification to vascular
      patterning into venous and arterial hierarchies. Following the initial assembly
      of ECs into a network of cord-like structures, vascular expansion and remodeling
      occur rapidly through morphogenetic events including vessel sprouting, fusion,
      and pruning. In addition, vascular morphogenesis encompasses the process of lumen
      formation, critical for the transformation of cords into perfusable vascular
      tubes. Studies in mouse, zebrafish, frog, and human endothelial cells have begun
      to outline the cellular and molecular requirements underlying lumen formation.
      Although the lumen can be generated through diverse mechanisms, the coordinated
      participation of multiple conserved molecules including transcription factors,
      small GTPases, and adhesion and polarity proteins remains a fundamental
      principle, leading us closer to a more thorough understanding of this complex
      event. 

PMID- 24323947
TI  - Transposable elements become active and mobile in the genomes of aging mammalian
      somatic tissues.
AB  - Transposable elements (TEs) were discovered by Barbara McClintock in maize and
      have since been found to be ubiquitous in all living organisms. Transposition is
      mutagenic and organisms have evolved mechanisms to repress the activity of their
      endogenous TEs. Transposition in somatic cells is very low, but recent evidence
      suggests that it may be derepressed in some cases, such as cancer development. We
      have found that during normal aging several families of retrotransposable
      elements (RTEs) start being transcribed in mouse tissues. In advanced age the
      expression culminates in active transposition. These processes are counteracted
      by calorie restriction (CR), an intervention that slows down aging.
      Retrotransposition is also activated in age-associated, naturally occurring
      cancers in the mouse. We suggest that somatic retrotransposition is a hitherto
      unappreciated aging process. Mobilization of RTEs is likely to be an important
      contributor to the progressive dysfunction of aging cells. 

PMID- 24323949
TI  - Study of the effect of vintage, maturity degree, and irrigation on the amino acid
      and biogenic amine content of a white wine from the Verdejo variety.
AB  - BACKGROUND: The aim of this study was to determine the effect of three factors
      directly related to the amino acid content of grapes and their interaction. These
      three factors were vintage, maturity degree and irrigation. The evolution of
      amino acid was also assessed during the winemaking along with the effect of
      maturity and irrigation on the biogenic amine formation. The grapes used for this
      study were of the Verdejo variety. RESULTS: The results indicated that there was
      a strong vintage effect on amino acid content in grapes, which seemed to be
      clearly related to climatic conditions. The effect of maturity on amino acid
      content depended on vintage, irrigation and the amino acid itself although it was
      observed that irrigation caused the increase of most amino acids present in the
      berry. Irrigation did not affect the evolution of nitrogen compounds during the
      alcoholic fermentation process but the maturity degree in some of the amino acids
      tested did so. No direct relationship could be established between irrigation or
      maturity degree and biogenic amines. However, it should be noted that the
      biogenic amine content was very low. CONCLUSIONS: Vintage has a strong effect on
      the amino acid content in grapes which appears to be related to weather
      conditions. No direct relationship has been found between irrigation or maturity
      degree and biogenic amines content. Furthermore, it is noted that biogenic amine
      content found in final wines was very low.

PMID- 24323948
TI  - In Pichia pastoris, growth rate regulates protein synthesis and secretion, mating
      and stress response.
AB  - Protein production in yeasts is related to the specific growth rate MU. To
      elucidate on this correlation, we studied the transcriptome of Pichia pastoris at
      different specific growth rates by cultivating a strain secreting human serum
      albumin at MU = 0.015 to 0.15 h(-1) in glucose-limited chemostats. Genome-wide
      regulation revealed that translation-related as well as mitochondrial genes were
      upregulated with increasing MU, while autophagy and other proteolytic processes,
      carbon source-responsive genes and other targets of the TOR pathway as well as
      many transcriptional regulators were downregulated at higher MU. Mating and
      sporulation genes were most active at intermediate MU of 0.05 and 0.075 h(-1) .
      At very slow growth (MU = 0.015 h(-1) ) gene regulation differs significantly,
      affecting many transporters and glucose sensing. Analysis of a subset of genes
      related to protein folding and secretion reveals that unfolded protein response
      targets such as translocation, endoplasmic reticulum genes, and cytosolic
      chaperones are upregulated with increasing growth rate while proteolytic
      degradation of secretory proteins is downregulated. We conclude that a high MU
      positively affects specific protein secretion rates by acting on multiple
      cellular processes. 

PMID- 24323950
TI  - Fertility and developmental toxicity assessment in rats and rabbits with
      LY500307, a selective estrogen receptor beta (ERbeta) agonist.
AB  - LY500307 is a selective estrogen receptor beta (ERbeta) agonist that was
      developed for the treatment of benign prostatic hyperplasia. The in vitro
      functional selectivity of LY500307 for ERbeta agonist activity is 32-fold above
      the activity at the alpha receptor (ERalpha). LY500307 was evaluated in a series
      of male (M) and female (F) rat fertility and rat and rabbit embryo-fetal
      development (EFD) studies, using 20 or 25 animals/group. LY500307 was
      administered daily by oral gavage starting 2 weeks (F) or 10 weeks (M) before
      mating, during cohabitation, until necropsy (M) or through gestation day (GD) 6
      (F) in the fertility studies and from GD 6 to 17 (rats) or GD 7 to 19 (rabbits)
      in the EFD studies. Dosage levels of LY500307 ranged from 0.03 to 10 mg/kg/day
      for rats and from 1 to 25 mg/kg/day for rabbits. Fertility, estrous, maternal
      reproductive endpoints, conceptus viability, sperm parameters, organ weights, and
      histopathology were evaluated in the fertility studies. Maternal reproductive
      endpoints and fetal viability, weight, and morphology were evaluated in the EFD
      studies. Toxicokinetics were assessed in satellite animals. At 10 mg/kg/day in
      the male fertility study, findings included decreased body weight (BW); food
      consumption (FC); fertility, mating, and conception indices; sperm concentration;
      and reproductive tissue weight (associated with atrophic histologic changes). In
      the female fertility study, effects included decreased BW and FC at >=0.3
      mg/kg/day and persistent diestrus, delayed mating, and reduced
      fertility/conception indices at 3 mg/kg/day. In the rat EFD study, findings
      included decreased maternal BW and FC and increased incidences of adverse
      clinical signs, abortion, maternal mortality/moribundity, postimplantation loss,
      and fetal skeletal variations at 3 mg/kg/day. Effects in the rabbit EFD study
      were limited to decreases in maternal BW and FC at 25 mg/kg/day. In general,
      systemic maternal exposure increased proportionally with dosage in rats, but less
      than proportionally in rabbits. In conclusion, the no-observed adverse effect
      levels following LY500307 administration were 1 mg/kg/day for male rat fertility,
      0.3 mg/kg/day for female rat fertility and EFD, and 25 mg/kg/day for rabbit EFD.
      Adverse reproductive and developmental effects only occurred at or above
      parentally toxic dosage levels and were considered predominantly due to off
      target ERalpha effects. 

PMID- 24323952
TI  - Scaling of dorsal-ventral patterning in the Xenopus laevis embryo.
AB  - Scaling of pattern with size has been described and studied for over a century,
      yet its molecular basis is understood in only a few cases. In a recent, elegant
      study, Inomata and colleagues proposed a new model explaining how bone
      morphogenic protein (BMP) activity gradient scales with embryo size in the early
      Xenopus laevis embryo. We discuss their results in conjunction with an
      alternative model we proposed previously. The expansion-repression mechanism
      (ExR) provides a conceptual framework unifying both mechanisms. Results of
      Inomata and colleagues implicate the chordin-stabilizing protein sizzled as the
      expander molecule enabling scaling, while we attributed this role to the BMP
      ligand Admp. The two expanders may work in concert, as suggested by the
      mathematical model of Inomata et al. We discuss approaches for differentiating
      the contribution of sizzled and Admp to pattern scaling. 

PMID- 24323951
TI  - Completeness and usability of ethnicity data in UK-based primary care and
      hospital databases.
AB  - BACKGROUND: Ethnicity recording across the National Health Service (NHS) has
      improved dramatically over the past decade. This study profiles the completeness,
      consistency and representativeness of routinely collected ethnicity data in both
      primary care and hospital settings. METHODS: Completeness and consistency of
      ethnicity recording was examined in the Clinical Practice Research Datalink
      (CPRD) and Hospital Episode Statistics (HES), and the ethnic breakdown of the
      CPRD was compared with that of the 2011 UK censuses. RESULTS: 27.1% of all
      patients in the CPRD (1990-2012) have ethnicity recorded. This proportion rises
      to 78.3% for patients registered since April 2006. The ethnic breakdown of the
      CPRD is comparable to the UK censuses. 79.4% of HES inpatients, 46.8% of
      outpatients and 26.8% of A&E patients had their ethnicity recorded. Amongst those
      with ethnicity recorded on >1 occasion, consistency was over 90% in all data sets
      except for HES inpatients. Combining CPRD and HES increased completeness to 97%,
      with 85% of patients having the same ethnicity recorded in both databases.
      CONCLUSIONS: Using CPRD ethnicity from 2006 onwards maximizes completeness and
      comparability with the UK population. High concordance within and across NHS
      sources suggests these data are of high value when examining the continuum of
      care. Poor completeness and consistency of A&E and outpatient data render these
      sources unreliable.

PMID- 24323953
TI  - Gold-catalyzed [2+2+1] cycloaddition of 1,6-diyne carbonates and esters with
      aldehydes to 4-(cyclohexa-1,3-dienyl)-1,3-dioxolanes.
AB  - A synthetic method to stereoselectively prepare 4-(cyclohexa-1,3-dienyl)-1,3
      dioxolanes in good to excellent yields by gold(I)-catalyzed [2+2+1] cycloaddition
      of 1,6-diyne carbonates and esters with aldehydes is described. The cascade
      process involves 1,2-acyloxy migration followed by cyclopropenation and
      cycloreversion. This leads to an unprecedented [2+2+1] cycloaddition of the
      resulting alkenylgold carbenoid species, examples of which are extremely rare,
      with two aldehyde molecules at catalyst loadings as low as 1 mol %. The
      usefulness of this cycloisomerization chemistry was further demonstrated by the
      transformation of one example to the corresponding phenol. 

PMID- 24323954
TI  - Hexaazatrinaphthylenes with different twists.
AB  - A synthetic strategy that allows the induction of twist angles of different sizes
      in 5,6,11,12,17,18-hexaazatrinaphthylene (HATNA) chromophores is reported. The
      different twist angles are accompanied by measurable changes in the emission and
      electrochemical characteristics of HATNA. 

PMID- 24323955
TI  - Substrate replenishment and byproduct removal improve yeast cell-free protein
      synthesis.
AB  - Cell-free protein synthesis (CFPS) platforms are now considered a powerful tool
      for synthesizing a variety of proteins at scales from pL to 100 L with
      accelerated process development pipelines. We previously reported the advancement
      of a novel yeast-based CFPS platform. Here, we studied factors that cause
      termination of yeast CFPS batch reactions. Specifically, we characterized the
      substrate and byproduct concentrations in batch, fed-batch, and semi-continuous
      reaction formats through high-performance liquid chromatography (HPLC) and
      chemical assays. We discovered that creatine phosphate, the secondary energy
      substrate, and nucleoside triphosphates were rapidly degraded during batch CFPS,
      causing a significant drop in the reaction's energy charge (E.C.) and eventual
      termination of protein synthesis. As a consequence of consuming creatine
      phosphate, inorganic phosphate accumulated as a toxic byproduct. Additionally, we
      measured amino acid concentrations and found that aspartic acid was rapidly
      consumed. By adopting a semi-continuous reaction format, where passive diffusion
      enables substrate replenishment and byproduct removal, we achieved over a 70%
      increase in active superfolder green fluorescent protein (sfGFP) as compared with
      the batch system. This study identifies targets for the future improvement of the
      batch yeast CFPS reaction. Moreover, it outlines a detailed, generalized method
      to characterize and improve other CFPS platforms. 

PMID- 24323956
TI  - The first kidney transplant in HIV infected patient in Georgia.
AB  - Highly active antiretroviral therapy (HAART) has significantly improved the life
      expectancy of patients with HIV. As a result, kidney transplantation is
      considered an viable treatment option for HIV infected patients with end stage
      renal disease. The first living-related kidney transplant in Georgia has been
      performed between non-identical twin sisters in July 2013. In this paper we give
      the detailed case report and short overview of the existing literature. This is
      the first report of the successful kidney transplant in HIV infected patient in
      East Europe and former Soviet Union Countries including the Central Asia. 

PMID- 24323957
TI  - Transplanting kidneys with small renal masses: a new source of renal allografts.
AB  - The number of publications on transplanting kidneys with small renal masses is
      steadily growing. There are several transplant centers worldwide with organized
      programs of transplanting such kidneys. Nevertheless, despite growing number of
      reports this practice remains controversial. The existing guidelines for kidney
      transplantation give controversial recommendations concerning transplantation of
      the kidneys with renal masses. There are arguments in favour as well as against
      this policy. Importance of the subject is emphasized by calculations showing that
      about 3000 kidneys with tumors could be transplanted in the United States
      annually. Based on the results reported in the literature the risk of occurrence
      of de novo graft tumor is extremely low and varies from 0.24% to 0.46%. A risk of
      getting a transmitted cancer is even lower and reported as 0.015-0.2%. The
      patient and graft survival rates of these kidneys are comparable to that of the
      standard criteria deceased and living transplant. More studies with higher number
      of patients are needed to prove the functional and oncological safety of this
      practice. 

PMID- 24323958
TI  - Epidemiology of urolithiasis among the population of Balakan region of the
      Republic of Azerbaijan.
AB  - The aim of the research was to conduct the study of epidemiological risk-factors
      of urolithiasis in Balakan region according to age, sex and BMI. 176 from 10 to
      83 years old patients having cystic calculi disease that were assigned to
      hospital examination and treatment in Central Hospital of Balakan region during
      2007-2011 98 (55,68%) male and 78 (44,32%) female were investigated. The average
      age was 47,3+/-17,67 for general patient group, 49,79+/-19,75 in males and 43,5+/
      14,37 in females. The males/females ratio among the patients was 1,26:1. It was
      found that: a) the urinary stones with oxalate content were more frequent in
      people with overweight (25-29,9 kg/m2); b) the urinary stones with urate and
      phosphate content was more frequent in people with overweight (25-29,9 kg/m2) and
      in female group with normal weight (18,5-24,9 kg/m2). 

PMID- 24323959
TI  - [Biomechanical analysis of the functioning of resection prosthesis for upper
      jaw].
AB  - The thesis presents the main design cases, the possible functioning of resection
      prosthesis. The influence of the main parameters of hinge resection prosthesis in
      the moving up - down on efforts to support elements (teeth and implants) and the
      mucosal of the sky. Suitable for use in the clinic during the initial
      installation and regulation of the prosthesis by moving down to ensure good
      contact between the lower stop and the rod spring pin, which eliminates a feeling
      of "balancing" the prosthesis, and hence a feeling of discomfort for the patient.
      It is the proved that a significant decrease in "wrenching" the supporting teeth
      (implants) Moments of the can be achieved by placing additional support in the
      area of resection of the sky or on the edge of the healthy part of it. 

PMID- 24323960
TI  - Clinical specificities of Tinea capitis in Georgia population.
AB  - The aim of the study was to reveal peculiarities of the clinical symptoms and
      forms of Tinea capitis caused by etiological agents that are common in our
      country. The study was conducted on 176 ambulatory patients who approached the
      National Centre in 2009-2013. Inclusion criterion was simultaneous presence of
      clinical symptoms and positive result of microscopic study. For cultural
      examination was used Sabouraud's dextrose agar with the antibiotic
      chloramphenicol. Clinical manifestations were divided into inflammatory and non
      inflammatory (i.e. slightly manifested inflammatory signs) lesions. 85(48,3%)
      inflammatory and 91(51,7%) non-inflammatory cases of Tinea capitis were revealed.
      Clinical forms were distributed in following way: kerion 73 (41,5%), grey patch
      with single lesions 71 (40,3%), seborrheic dermatitis-like form 14 (8%), agminate
      folliculites 12 (6,8%) and black-dot dermatophytosis 6 (3,4%). In 41(89,1%) of
      the cases etiological agent of the kerion was Trichophyton mentagrophytes; in
      41(85,4%) of the cases etiological agent for the grey patch with single lesions
      was Microsporum canis. Important clinical and etiological relationship was
      revealed between kerion and Trichophyton mentagrophytes, as well as between grey
      patch with single lesions and Microsporum canis. In case of inflammatory forms
      (predominantly kerion) caused by Trichophyton verrucosum and Trichophyton
      mentagrophytes ID reaction was manifested by disseminated follicular papules. 

PMID- 24323961
TI  - [Clinical and immunological characteristics of hiv-infection in patients with
      Asp299glly polymorphism of the Toll-like receptor 4 gene].
AB  - The prevalence of Asp299Gly polymorphism of the TLR4 gene and its impact on the
      clinical and immunological characteristics of HIV infection were investigated.
      Asp299Gly polymorphism of the TLR4 gene was observed significantly in HIV
      infected patients - 12.0 % as compared with controls (2.1%, p<0,05). This study
      suggests a greater risk for development of viral, bacterial and parasitic
      infections in HIV- positive patients with Asp299Gly polymorphism of the TLR4
      gene. The patients with Asp299Gly TLR4 polymorphism demonstrated the development
      of opportunistic infections with higher CD-4 counts than the patients with AA
      genotype. The present results may influence to the future criteria for initiation
      antiretroviral treatment and antibiotic prophylaxis of opportunistic infections
      in patients with Asp299Gly polymorphism of the TLR 4 gene. 

PMID- 24323962
TI  - [The structure of type 2 diabetes risk-factors in people with normal weight].
AB  - In the current study we have presented the analyzed data of screening materials
      of type 2 diabetes patients aged 45 and above carried out in Kharkov (n=535) and
      Kharkov district villages (n=1052). It has been established, that the data of
      cohort people with normal body mass index were practically the same and accounted
      approximately one fourth of the analyzed patients. At the same time, it appeared
      that the patients living in the city were more susceptible to metabolic obesity
      (enlargement of abdominal fat tissue), arterial hypertension, myocardial
      infarction, insult and heavy family history. Metabolic obesity prevalent in city
      cohorts practically did not have any effect on the frequency of the above
      mentioned risk-factors. However, it definitely affected the cardio-vascular
      component in village cohorts. 

PMID- 24323963
TI  - [Optimization of stable angina standard therapy in patients with concomitant
      osteoarthritis and obesity].
AB  - The aim of the study was to optimize standard therapy in patients with stable
      angina pectoris (SAP) associated with osteoarthritis (OA) and obesity through a
      combined, concomitant therapy of OA and obesity. To address this goal, on a
      background of standard therapy of stable angina was carried concomitant therapy
      of osteoarthritis and obesity, which included non-steroidal anti-inflammatory
      drugs, a selective COX-2 inhibitors, chondro-protective agents, anti-diabetic
      drug from the group of biguanides (metformin), a drug that affects the centers of
      hunger and reduces appetite in obese patients "Tsefamadar" (active ingredient
      Trituration Madara D4 - 250 mg), as well as diet with reduced energetic
      properties, number 8, and its modification: 8a (for obese patients with I-II
      degree), 80 (for obese patients III degree). As a result of the proposed method
      of treatment had improved the clinical course of CCH due to lower body weight,
      body mass index (BMI) and abdominal obesity indexes (AOI), which were
      characterized by decreasing the duration and frequency of angina attacks,
      reducing the number of nitroglycerin tablets taken, and also increased exercise
      tolerance (ET). Correction of carbohydrate metabolism on the background of
      metformin treatment, helped to improve lipid metabolism, suggesting greater
      efficiency of HMG-CoA reductase inhibitors (statins) in patients with SAP on a
      background of the proposed method. The decrease in CRP levels in patients with
      SAP, combined with OA and obesity with concomitant therapy by the proposed
      method, indicates a decrease in systemic inflammation. 

PMID- 24323964
TI  - [Features of the influence of functional pathology of the digestive system
      combining with neurocirculatory dystonia on quality of life of students'
      population].
AB  - The study of 139 persons from organized student population is presented. The
      results of the frequency of occurrence of functional diseases of the digestive
      system combining with neurocirculatory dystonia in this age group are
      illustrated. It is shown that all indices of the quality of life are decreased in
      patients with comorbid functional disorders according to the results of the
      questionnaire "SF-36 Health Status Survey" (SF-36). The most pronounced reduction
      was set for such indices as RP, GH, VT, RE and MH and was more typical for
      patients with irritable bowel syndrome and the "overlap syndrome" of functional
      disorders of the digestive system combining with the autonomic dysfunction. High
      degree of reduction of the "mental health component" (MH sum) in all groups was
      demonstrated which confirms the particular impact of functional pathology on the
      psychological state of young persons. 

PMID- 24323965
TI  - [Clinical-pathogenic role of the functional condition of vegetative nervous
      system in progressive the mixed cryoglobulinemia in patients with chronic
      hepatitis C].
AB  - The study of 304 patients with chronic hepatitis C is presented. It was shown
      that in patients with chronic hepatitis C the occurrence and increase of
      violations of a functional condition of vegetative nervous system it is combined
      with emergence and progressing of signs of the mixed cryoglobulinemia. Clinical
      demonstration of the HCV associated crioglobulinemia syndrome is accompanied by
      the most expressed vegetative dysfunction, the being characterized low capacity
      of variability of a rhythm of heart and development of a vegetative disbalance
      and sympathicotonia. 

PMID- 24323966
TI  - Comparative phenotypic characterization of Vibrio cholerae isolates collected
      from aquatic environments of Georgia.
AB  - Vibrio cholerae is ubiquitous in aquatic environment inhabiting marine, fresh and
      brackish waters. V. cholerae serotypes O1 and O139 cause the devastating
      diarrheal disease cholera, which is often fatal without proper treatment. Little
      is known regarding the abundance and diversity of clinically important
      nonhalophilic vibrios in the South Caucasus region, particularly in Georgia. Here
      we provide the data on the Georgian environmental strains of V. cholerae isolated
      in 2006-2009 years from the coastal waters of the Black Sea and inland water
      reservoirs near Tbilisi. In total, 846 V. cholerae strains were collected from
      the water samples, most of them (705 strains) obtained from fresh water lakes.
      Isolation pattern of V. cholerae showed obvious seasonality with the highest
      isolation rates in late summer - early autumn. Twenty-nine isolates of V.
      cholerae were attributed to the O1 serotype based on serological studies and PCR
      identification and were further grouped by biochemical properties into classical
      and El Tor biotypes as well as hybrids. The study of antibiotic susceptibility
      profiles for V. cholerae isolates showed that 95% were sensitive to tetracycline,
      91% to doxycycline, and 91% to ciprofloxacin. Interestingly, the freshwater
      isolates appeared to be more resistant to antibiotics than the Black Sea
      isolates. Among Black Sea isolates of V. cholerae toxigenic strains of O1
      serotype revealed higher antibiotic resistance compared to non- O1/non-O139
      isolates. In addition, V. cholerae O1 and non- O1/non-O139 isolates differed by
      phage susceptibility profiles, with higher diversity within the population of
      environmental non-O1/non-O139 V. cholerae isolates. 

PMID- 24323967
TI  - Ivy water extracts as gastric ulcer preventive agents.
AB  - In folk medicine the ivies (Hedera L. Fam.Araliaceae) are known as plants
      possessing diverse curative properties. A comparative phytochemical study of the
      biologically active water extracts of H. colchica and H. helix and evaluation of
      their ulcer preventive efficacy in ethanol-induced ulcer model in rats was
      carried out. Water extracts of H. colchica and H. helix (300 mg/kg, i.p.)
      significantly (p<0.01) decrease the ulcer index (0.50 and 1.38 vs 3.17 in
      control) and rise macroscopic curative ratio (84.2% and 56.6%, respectively). The
      results clearly indicate that pretreatment with water extract of H. colchica is
      preferable and further experiments are required to isolate the active principals
      responsible for itsantiulcerogenic activity. 

PMID- 24323968
TI  - Influence of serial electrical stimulations of perifornical and posterior
      hypothalamic orexin-containing neurons on regulation of sleep homeostasis and
      sleep-wakefulness cycle recovery from experimental comatose state and anesthesia
      induced deep sleep.
AB  - The work was aimed for the ascertainment of following question - whether Orexin
      containing neurons of dorsal and lateral hypothalamic, and brain Orexinergic
      system in general, are those cellular targets which can speed up recovery of
      disturbed sleep homeostasis and accelerate restoration of sleep-wakefulness cycle
      phases during some pathological conditions - experimental comatose state and/or
      deep anesthesia-induced sleep. Study was carried out on white rats. Modeling of
      experimental comatose state was made by midbrain cytotoxic lesions at intra
      collicular level.Animals were under artificial respiration and special care.
      Different doses of Sodium Ethaminal were used for deep anesthesia. 30 min after
      comatose state and/or deep anesthesia induced sleep serial electrical
      stimulations of posterior and/or perifornical hypothalamus were started.
      Stimulation period lasted for 1 hour with the 5 min intervals between subsequent
      stimulations applied by turn to the left and right side hypothalamic parts.EEG
      registration of cortical and hippocampal electrical activity was started
      immediately after experimental comatose state and deep anesthesia induced sleep
      and continued continuously during 72 hour. According to obtained new evidences,
      serial electrical stimulations of posterior and perifornical hypothalamic Orexin
      containing neurons significantly accelerate recovery of sleep homeostasis,
      disturbed because of comatose state and/or deep anesthesia induced sleep. Speed
      up recovery of sleep homeostasis was manifested in acceleration of coming out
      from comatose state and deep anesthesia induced sleep and significant early
      restoration of sleep-wakefulness cycle behavioral states. 

PMID- 24323969
TI  - [The variants of changes in pro- and antioxidative processes in viral hepatitis
      and the necessity of differential approach in their antioxidative therapy].
AB  - There was investigated the changes in pro- and antioxidative processes in viral
      hepatitis of different etiology. It was revealed that the mechanisms mentioned
      above essentially differ from each other and for their treatment, accordingly,
      different groups of antioxidative drugs should be used. The data obtained
      indicates the impossibility of "universal" antioxidative therapy. The role of
      oxidative stress in the mechanisms of different types of hepatitis and unforeseen
      negative effect of antioxidative therapy requires special caution and attention
      in selection of mitochondrial respiratory chain stabilizing antioxidants. In
      hepatitis A, which is characterized by relatively less intensity of peroxidation
      natural antiradical remedies should be used (e.g. tocopherol). In viral hepatitis
      B and especially in hepatitis C, it is desirable to use the selenium-containing
      antioxidants. In hepatitis B, which is characterized by relatively less content
      of nitric oxide, it is recommended to use the stimulants of NO synthesis. 

PMID- 24323970
TI  - [Genome instability in pulmonary tuberculosis before and after treatment].
AB  - Pulmonary tuberculosis is classified as a disease with a genetic predisposition,
      and therefore, as with other pathologies related to this group of diseases, by
      pulmonary tuberculosis, special importance is given to finding those markers that
      enable early identification of risk groups, such as skrinnig in general
      population and relatives of patients with tuberculosis, which in turn can provide
      the basis for preventive measures. One of this markers is the level of genome
      stability. The aim of this study was a comparative evaluation of the functional
      parameters of the genome variability in patients with sensitive form of pulmonary
      tuberculosis before and after treatment, and the possibility of its correction
      with anti-stress peptide bioregulator - epitalon. The studies were conducted
      using short-term mitoge -stimulated cell cultures of TB patients, before and
      after treatment. As an indicator of genome stability has been studied the
      frequency of structural and numerical chromosome aberrations and fragile sites.
      It is shown, that in intact cultures from patients with pulmonary tuberculosis,
      before treatment was significantly higher level of frequency of cells with
      structural chromosome aberrations, that still retained after the treatment. As
      for epithalon, it appears that was shown a pronounced protective effect after
      treatment, on the test of chromosome aberrations, by reducing both overall mean
      frequency aberrant cells and indicators for all individuals. In the study of
      fragility of chromosomes in patients with primary tuberculosis was found, that in
      intact cultures, the proportion of cells with chromosomal fragile sites was
      higher than in control group of healthy individuals, befor and after treatment.
      High frequency of chromosome fragility persisted by treatment with peptide
      bioregulator in both cases - before and after treatment. It is suggested that the
      identified patterns can be correlated with a high incidence of re- TB. 

PMID- 24323971
TI  - [The fatty acid composition of Ruta graveolens seed oil and its byological
      activity].
AB  - Using high-performance liquid chromatography methods are qualitatively and
      quantitatively identified most biological important high fatty acids, contained
      in Ruta graveolens seed oil grown on the experimental plot of Kutateladze
      Institute of Pharmakochemistry (Georgia) and compare its biological activity.
      Their relative concentration is expressed as percentages of the total fatty acid
      component. The sample contained the range of fatty acids from S12:0 to S22:0. The
      investigation showed different sensitivity of components. In order of elution the
      list of compound are reported. The oil contained 2,08+/-0,1 mg% lauric, 2,18+/
      0,1 mg% miristic, 3,98+/-0,1 mg% palmitic, 30,90+/-1,2 mg% stearic, 41,92+/-1,8
      mg% oleic, 10,14+/-0,4 mg% linolic, 6,50+/-0,3 mg% linolenic, 2,00+/-0,1 mg%
      arachinic and 2,10+/-0,1 mg% begenic acid. The chromatography signals with
      retention values 7,96 and 14,08 minuts are qualitatively not identified. 

PMID- 24323972
TI  - [Alkaloids of Vinca rosea L. introduced to Western Georgia].
AB  - Vinca roseae L. (Satharanthus rosea (L.) G. Don) was introduced at Kobuleti
      experimental station of medical plants. The object of investigation was the plant
      material of Vinca roseae L. collected in May, 2005., September, 2006 and October,
      2009. Total alkaloids were obtained in accordance with Atta- ur-Rachman method.
      The variability of the quantitative and qualitative composition of total
      alkaloids and vincaleikoblastin (VLB) fraction during vegetation was studied. It
      was established that the maximal content of total alkaloids and VLB fraction of
      Vinca roseae L. is accumulated in the phase of secondary flowering, hence the
      collecting of a plant material is recommended to be made during the aforesaid
      vegetation phase as for this period it is a rather high output of a raw material,
      alkaloid complex and VLB faction. Alkaloids vinkaleikoblastin, ajmalicine and new
      epimer tetrahydroalstonine with S3N-alpha- orientation were yielded, separated
      and identified using modern physical-chemical and spectral methods (13S NMR). 

PMID- 24323973
TI  - Fiberfox: facilitating the creation of realistic white matter software phantoms.
AB  - PURPOSE: Phantom-based validation of diffusion-weighted image processing
      techniques is an important key to innovation in the field and is widely used.
      Openly available and user friendly tools for the flexible generation of tailor
      made datasets for the specific tasks at hand can greatly facilitate the work of
      researchers around the world. METHODS: We present an open-source framework,
      Fiberfox, that enables (1) the intuitive definition of arbitrary artificial white
      matter fiber tracts, (2) signal generation from those fibers by means of the most
      recent multi-compartment modeling techniques, and (3) simulation of the actual MR
      acquisition that allows for the introduction of realistic MRI-related effects
      into the final image. RESULTS: We show that real acquisitions can be closely
      approximated by simulating the acquisition of the well-known FiberCup phantom. We
      further demonstrate the advantages of our framework by evaluating the effects of
      imaging artifacts and acquisition settings on the outcome of 12 tractography
      algorithms. CONCLUSION: Our findings suggest that experiments on a realistic
      software phantom might change the conclusions drawn from earlier hardware phantom
      experiments. Fiberfox may find application in validating and further developing
      methods such as tractography, super-resolution, diffusion modeling or artifact
      correction.

PMID- 24323974
TI  - Using dual-purpose crops in sheep-grazing systems.
AB  - The utilisation of dual-purpose crops, especially wheat and canola grown for
      forage and grain production in sheep-grazing systems, is reviewed. When sown
      early and grazed in winter before stem elongation, later-maturing wheat and
      canola crops can be grazed with little impact on grain yield. Recent research has
      sought to develop crop- and grazing-management strategies for dual-purpose crops.
      Aspects examined have been grazing effects on crop growth, recovery and yield
      development along with an understanding of the grazing value of the crop fodder,
      its implications for animal nutrition and grazing management to maximise live
      weight gain. By alleviating the winter 'feed gap', the increase in winter
      stocking rate afforded by grazing crops allows crop and livestock production to
      be increased simultaneously on the same farm. Integration of dual-purpose wheat
      with canola on mixed farms provides further systems advantages related to widened
      operational windows, weed and disease control and risk management. Dual-purpose
      crops are an innovation that has potential to assist in addressing the global
      food-security challenge.

PMID- 24323975
TI  - Activating mutations cluster in the "molecular brake" regions of protein kinases
      and do not associate with conserved or catalytic residues.
AB  - Mutations leading to activation of proto-oncogenic protein kinases (PKs) are a
      type of drivers crucial for understanding tumorogenesis and as targets for
      antitumor drugs. However, bioinformatics tools so far developed to differentiate
      driver mutations, typically based on conservation considerations, systematically
      fail to recognize activating mutations in PKs. Here, we present the first
      comprehensive analysis of the 407 activating mutations described in the
      literature, which affect 41 PKs. Unexpectedly, we found that these mutations do
      not associate with conserved positions and do not directly affect ATP binding or
      catalytic residues. Instead, they cluster around three segments that have been
      demonstrated to act, in some PKs, as "molecular brakes" of the kinase activity.
      This finding led us to hypothesize that an auto inhibitory mechanism mediated by
      such "brakes" is present in all PKs and that the majority of activating mutations
      act by releasing it. Our results also demonstrate that activating mutations of
      PKs constitute a distinct group of drivers and that specific bioinformatics tools
      are needed to identify them in the numerous cancer sequencing projects currently
      underway. The clustering in three segments should represent the starting point of
      such tools, a hypothesis that we tested by identifying two somatic mutations in
      EPHA7 that might be functionally relevant. 

PMID- 24323976
TI  - Virtual fetal laryngoscopy.

PMID- 24323977
TI  - TPS(PET)-A TPS-based approach for in vivo dose verification with PET in proton
      therapy.
AB  - Since the interest in ion-irradiation for tumour therapy has significantly
      increased over the last few decades, intensive investigations are performed to
      improve the accuracy of this form of patient treatment. One major goal is the
      development of methods for in vivo dose verification. In proton therapy, a PET
      (positron emission tomography)-based approach measuring the irradiation-induced
      tissue activation inside the patient has been already clinically implemented. The
      acquired PET images can be compared to an expectation, derived under the
      assumption of a correct treatment application, to validate the particle range and
      the lateral field position in vivo. In the context of this work, TPSPET is
      introduced as a new approach to predict proton-irradiation induced three
      dimensional positron emitter distributions by means of the same algorithms of the
      clinical treatment planning system (TPS). In order to perform additional activity
      calculations, reaction-channel-dependent input positron emitter depth
      distributions are necessary, which are determined from the application of a
      modified filtering approach to the TPS reference depth dose profiles in water.
      This paper presents the implementation of TPSPET on the basis of the research
      treatment planning software treatment planning for particles. The results are
      validated in phantom and patient studies against Monte Carlo simulations, and
      compared to beta(+)-emitter distributions obtained from a slightly modified
      version of the originally proposed one-dimensional filtering approach applied to
      three-dimensional dose distributions. In contrast to previously introduced
      methods, TPSPET provides a faster implementation, the results show no sensitivity
      to lateral field extension and the predicted beta(+)-emitter densities are fully
      consistent to the planned treatment dose as they are calculated by the same
      pencil beam algorithms. These findings suggest a large potential of the
      application of TPSPET for in vivo dose verification in the daily clinical
      routine. 

PMID- 24323978
TI  - DNA concentration can specify DNA melting point in a high-resolution melting
      analysis master mix.

PMID- 24323979
TI  - Interlaboratory agreement of insulin-like growth factor 1 concentrations measured
      by mass spectrometry.
AB  - BACKGROUND: Insulin-like growth factor 1 (IGF-1)(7) is a key mediator of growth
      hormone (GH) action and a well-characterized biomarker of GH abuse. Current
      immunoassays for IGF-1 suffer from poor concordance between platforms, which
      makes comparison of results between laboratories difficult. Although previous
      work has demonstrated good interlaboratory imprecision of LC-MS/MS methods when
      plasma is supplemented with purified proteins, the interlaboratory imprecision of
      an endogenous protein in the nanogram-per-milliliter concentration range has not
      been reported. METHODS: We deployed an LC-MS/MS method to quantify serum IGF-1 in
      5 laboratories using 5 different instruments and analyzed 130 healthy human
      samples and 22 samples from patients with acromegaly. We determined measurement
      imprecision (CV) for differences due to instrumentation, calibration curve
      construction, method of calibration, and reference material. RESULTS: Instrument
      dependent variation, exclusive of digestion, across 5 different instrument
      platforms was determined to be 5.6%. Interlaboratory variation was strongly
      dependent on calibration. Calibration materials from a single laboratory resulted
      in less variation than materials made in individual laboratories (CV 5.2% vs
      12.8%, respectively). The mean imprecision for 152 samples between the 5
      laboratories was 16.0% when a calibration curve was made in each laboratory and
      11.1% when a single-point calibration approach was used. CONCLUSIONS: The
      interlaboratory imprecision of serum IGF-1 concentrations is acceptable for use
      of the assay in antidoping laboratories and in standardizing results across
      clinical laboratories. The primary source of variability is not derived from the
      sample preparation but from the method of calibration.

PMID- 24323980
TI  - Circulating tumor cell isolation: a marathon race worth running.

PMID- 24323981
TI  - What lies beyond del(5q) in myelodysplastic syndrome?

PMID- 24323982
TI  - The role of antibiotic stewardship in limiting antibacterial resistance among
      hematology patients.

PMID- 24323983
TI  - European guidelines for empirical antibacterial therapy for febrile neutropenic
      patients in the era of growing resistance: summary of the 2011 4th European
      Conference on Infections in Leukemia.
AB  - Owing to increasing resistance and the limited arsenal of new antibiotics,
      especially against Gram-negative pathogens, carefully designed antibiotic
      regimens are obligatory for febrile neutropenic patients, along with effective
      infection control. The Expert Group of the 4(th) European Conference on
      Infections in Leukemia has developed guidelines for initial empirical therapy in
      febrile neutropenic patients, based on: i) the local resistance epidemiology; and
      ii) the patient's risk factors for resistant bacteria and for a complicated
      clinical course. An 'escalation' approach, avoiding empirical carbapenems and
      combinations, should be employed in patients without particular risk factors. A
      'de-escalation' approach, with initial broad-spectrum antibiotics or
      combinations, should be used only in those patients with: i) known prior
      colonization or infection with resistant pathogens; or ii) complicated
      presentation; or iii) in centers where resistant pathogens are prevalent at the
      onset of febrile neutropenia. In the latter case, infection control and
      antibiotic stewardship also need urgent review. Modification of the initial
      regimen at 72-96 h should be based on the patient's clinical course and the
      microbiological results. Discontinuation of antibiotics after 72 h or later
      should be considered in neutropenic patients with fever of unknown origin who are
      hemodynamically stable since presentation and afebrile for at least 48 h,
      irrespective of neutrophil count and expected duration of neutropenia. This
      strategy aims to minimize the collateral damage associated with antibiotic
      overuse, and the further selection of resistance. 

PMID- 24323986
TI  - Incidence and biological significance of IKZF1/Ikaros gene deletions in pediatric
      Philadelphia chromosome negative and Philadelphia chromosome positive B-cell
      precursor acute lymphoblastic leukemia.

PMID- 24323987
TI  - Impact of chemotherapy on venous thromboembolism: comment to: regional lymph node
      metastases are a strong risk factor for venous thromboembolism: results from the
      Vienna Cancer and Thrombosis Study.

PMID- 24323984
TI  - Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic
      stem cell transplant recipients: guidelines of the 4th European Conference on
      Infections in Leukemia (ECIL-4, 2011).
AB  - The detection of multi-resistant bacterial pathogens, particularly those to
      carbapenemases, in leukemic and stem cell transplant patients forces the use of
      old or non-conventional agents as the only remaining treatment options. These
      include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram
      positive agents. Data on the use of these agents in leukemic patients are scanty,
      with only linezolid subjected to formal trials. The Expert Group of the 4(th)
      European Conference on Infections in Leukemia has developed guidelines for their
      use in these patient populations. Targeted therapy should be based on (i) in
      vitro susceptibility data, (ii) knowledge of the best treatment option against
      the particular species or phenotype of bacteria, (iii)
      pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk
      benefit balance. For infections due to resistant Gram-negative bacteria, these
      agents should be preferably used in combination with other agents that remain
      active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk
      of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs
      in the near future should lead us to limit the use of these drugs to situations
      where no alternative exists.

PMID- 24323988
TI  - Immunotherapy-based regimen in anti-MAG neuropathy: results in 45 patients.

PMID- 24323989
TI  - Mutation spectrum in Chinese patients affected by congenital sideroblastic anemia
      and a search for a genotype-phenotype relationship.

PMID- 24323990
TI  - FLT3-ITD confers poor prognosis in patients with acute promyelocytic leukemia
      treated with AIDA protocols: long-term follow-up analysis.

PMID- 24323991
TI  - Impact of IKZF1 deletions on IKZF1 expression and outcome in Philadelphia
      chromosome negative childhood BCP-ALL. Reply to "incidence and biological
      significance of IKZF1/Ikaros gene deletions in pediatric Philadelphia chromosome
      negative and Philadelphia chromosome positive B-cell precursor acute
      lymphoblastic leukemia".

PMID- 24323992
TI  - First description of the t(10;11)(q22;q23)/MLL-TET1 translocation in a T-cell
      lymphoblastic lymphoma, with subsequent lineage switch to acute myelomonocytic
      myeloid leukemia.

PMID- 24323993
TI  - Residual scarring from hidradenitis suppurativa: fractionated CO2 laser as a
      novel and noninvasive approach.
AB  - Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin
      condition that can have a significant psychosocial impact, both with the active
      disease and with residual scarring. Although a wide variety of treatment options
      exist for HS, to our knowledge there are no reported modalities aimed
      specifically at treating HS scarring. We describe the case of an adolescent
      female who received medical management of intramammary HS followed by successful
      treatment with fractionated 10,600-nm carbon dioxide laser for her residual
      cribriform scarring. We believe there is great potential for the use of
      fractionated carbon dioxide laser to improve short- and long-term psychosocial
      outcomes of HS, promote physical scar remodeling, and possibly alter the disease
      process itself.

PMID- 24323994
TI  - Characteristics of youth seeking emergency care for assault injuries.
AB  - OBJECTIVE: To characterize youth seeking care for assault injuries, the context
      of violence, and previous emergency department (ED) service utilization to inform
      ED-based injury prevention. METHODS: A consecutive sample of youth (14-24)
      presenting to an urban ED with an assault injury completed a survey of partner
      violence, gun/knife victimization, gang membership, and context of the fight.
      RESULTS: A total of 925 youth entered the ED with an assault injury; 718
      completed the survey (15.4% refused); 730 comparison youth were sampled. The
      fights leading to the ED visit occurred at home (37.6%) or on streets (30.4%),
      and were commonly with a known person (68.3%). Fights were caused by issues of
      territory (23.3%) and retaliation (8.9%); 20.8% of youth reported substance use
      before the fight. The assault-injured group reported more peer/partner violence
      and more gun experiences. Assault-injured youth reported higher past ED
      utilization for assault (odds ratio [OR]: 2.16) or mental health reasons (OR:
      7.98). Regression analysis found the assault-injured youth had more frequent
      weapon use (OR: 1.25) and substance misuse (OR: 1.41). CONCLUSIONS: Assault
      injured youth seeking ED care report higher levels of previous violence, weapon
      experience, and substance use compared with a comparison group seeking care for
      other complaints. Almost 10% of assault-injured youth had another fight-related
      ED visit in the previous year, and ~5% had an ED visit for mental health. Most
      fights were with people known to them and for well-defined reasons, and were
      therefore likely preventable. The ED is a critical time to interact with youth to
      prevent future morbidity.

PMID- 24323996
TI  - The influence of Community Access to Child Health (CATCH) program on community
      pediatrics.
AB  - The CATCH (Community Access to Child Health) Program, which supports
      pediatricians who engage with the community to improve child health, increase
      access to health care, and promote advocacy through small seed grants, was last
      evaluated in 1998. The objective was to describe the characteristics of CATCH
      grant recipients and projects and assess the community impact of funded projects.
      Prospective data was collected from CATCH applications (grantee characteristics,
      topic area and target population for projects funded from 2006-2012) and post
      project 2-year follow-up survey (project outcomes, sustainability, and impact for
      projects funded from 2008 through 2010). From 2006 through 2012, the CATCH
      Program awarded 401 projects to grantees working mostly in general pediatrics.
      Eighty-five percent of projects targeted children covered by Medicaid, 33%
      targeted uninsured children, and 75% involved a Latino population. Main topic
      areas addressed were nutrition, access to health care, and medical home. Sixty
      nine percent of grantees from 2008 to 2010 responded to the follow-up survey.
      Ninety percent reported completing their projects, and 86% of those projects
      continued to exist in some form. Grantees reported the development of community
      partnerships (77%) and enhanced recognition of child health issues in the
      community (73%) as the most frequent changes due to the projects. The CATCH
      Program funds community-based projects led by pediatricians that address the
      medical home and access to care. A majority of these projects and community
      partnerships are sustained beyond their original CATCH funding and, in many
      cases, are leveraged into additional financial or other community support. 

PMID- 24323995
TI  - Comorbidity clusters in autism spectrum disorders: an electronic health record
      time-series analysis.
AB  - OBJECTIVE: The distinct trajectories of patients with autism spectrum disorders
      (ASDs) have not been extensively studied, particularly regarding clinical
      manifestations beyond the neurobehavioral criteria from the Diagnostic and
      Statistical Manual of Mental Disorders. The objective of this study was to
      investigate the patterns of co-occurrence of medical comorbidities in ASDs.
      METHODS: International Classification of Diseases, Ninth Revision codes from
      patients aged at least 15 years and a diagnosis of ASD were obtained from
      electronic medical records. These codes were aggregated by using phenotype-wide
      association studies categories and processed into 1350-dimensional vectors
      describing the counts of the most common categories in 6-month blocks between the
      ages of 0 to 15. Hierarchical clustering was used to identify subgroups with
      distinct courses. RESULTS: Four subgroups were identified. The first was
      characterized by seizures (n = 120, subgroup prevalence 77.5%). The second (n =
      197) was characterized by multisystem disorders including gastrointestinal
      disorders (prevalence 24.3%) and auditory disorders and infections (prevalence
      87.8%), and the third was characterized by psychiatric disorders (n = 212,
      prevalence 33.0%). The last group (n = 4316) could not be further resolved. The
      prevalence of psychiatric disorders was uncorrelated with seizure activity (P =
      .17), but a significant correlation existed between gastrointestinal disorders
      and seizures (P < .001). The correlation results were replicated by using a
      second sample of 496 individuals from a different geographic region. CONCLUSIONS:
      Three distinct patterns of medical trajectories were identified by unsupervised
      clustering of electronic health record diagnoses. These may point to distinct
      etiologies with different genetic and environmental contributions. Additional
      clinical and molecular characterizations will be required to further delineate
      these subgroups.

PMID- 24323997
TI  - Violent film characters' portrayal of alcohol, sex, and tobacco-related
      behaviors.
AB  - OBJECTIVE: To determine the extent to which movies popular with adolescents
      feature characters who jointly engage in violence and other risk behaviors. We
      hypothesized that violent characters engage in other risk behaviors equally often
      in films rated appropriate for children over 12 (PG-13) and Restricted (R)-rated
      films. METHODS: Content analysis of a sample of top-grossing movies from 1985 to
      2010 (n = 390). We coded movies for the presence of at least 1 main character who
      was involved in violence and either sex, tobacco, or alcohol use within a 5
      minute movie segment and throughout a film. RESULTS: Approximately 90% of the
      movies contained a segment with a main character involved in violence, and ~77%
      of the films had the same character engaging in at least 1 other risk behavior. A
      violent character was portrayed most often partaking in alcohol-related and
      sexual behaviors. G and PG movies had less co-occurrence than PG-13 or R-rated
      movies, but there was no statistical difference between PG-13 and R-rated movies
      with regards to violence co-occurring with other risk behaviors. These trends did
      not vary over time. CONCLUSIONS: Popular films that contain violent characters
      also show those characters engaging in other risk behaviors. Similar rates of co
      occurrence between PG-13 and R-rated films suggest that the Motion Picture
      Association of America ratings system is not sensitive to the joint portrayal of
      violence and alcohol, sex, and tobacco-related risk behaviors. The on-screen
      clustering of violence with other risk behaviors is cause for concern and worthy
      of additional research.

PMID- 24323998
TI  - Perceptions of 24/7 in-hospital intensivist coverage on pediatric housestaff
      education.
AB  - BACKGROUND: In recent years, the focus on patient safety and housestaff
      supervision has led to a steady increase in institutions providing 24/7 in
      hospital (also known as in-house, henceforth referred to as IH) coverage by
      pediatric intensivists. Effects of this increased attending physician presence on
      education of pediatric housestaff have not been studied. We hypothesized that IH
      coverage would decrease perceived autonomy of housestaff and negatively affect
      their preparedness to be independent attending physicians on completion of
      training. METHODS: A secure, anonymous, Web-based survey was sent to pediatric
      intensivists in the United States and Canada, and pediatric critical care fellows
      and pediatric residents at academic centers across the United States. Questions
      focused on perceptions of IH coverage and housestaff educational experience.
      RESULTS: We report 1323 responses from 147 institutions (center response rate
      74%). Although 96% of respondents stated that the PICU provides "a good
      educational experience," only 50% of pediatric intensivists and 67% of housestaff
      feel that housestaff are prepared for independent practice after training in an
      IH model. Compared with those training in home-call models, respondents currently
      working in IH models have more favorable perceptions of the effects of IH
      coverage on housestaff autonomy (P < .0001), supervision (P < .0001), and
      preparation for independent practice (P < .0001). CONCLUSIONS: Pediatric
      intensivists and housestaff express concern regarding the preparation of
      housestaff training in a 24/7 IH attending model. An important priority for
      institutions using or considering a 24/7 IH attending coverage model is the
      balance between adequate housestaff supervision and autonomy.

PMID- 24323999
TI  - 24/7 attendings: "helicoptering" the housestaff?

PMID- 24324000
TI  - Impact of a bronchiolitis guideline on ED resource use and cost: a segmented time
      series analysis.
AB  - OBJECTIVE: Bronchiolitis is a major cause of infant morbidity and contributes to
      millions of dollars in health care costs. Care guidelines may cut costs by
      reducing unnecessary resource utilization. Through the implementation of a
      guideline, we sought to reduce unnecessary resource utilization and improve the
      value of care provided to infants with bronchiolitis in a pediatric emergency
      department (ED). METHODS: We conducted an interrupted time series that examined
      ED visits of 2929 patients with bronchiolitis, aged 1 to 12 months old, seen
      between November 2007 and April 2013. Outcomes were proportion having a chest
      radiograph (CXR), respiratory syncytial virus (RSV) testing, albuterol or
      antibiotic administration, and the total cost of care. Balancing measures
      included admission rate, returns to the ED resulting in admission within 72 hours
      of discharge, and ED length of stay (LOS). RESULTS: There were no significant
      preexisting trends in the outcomes. After guideline implementation, there was an
      absolute reduction of 23% in CXR (95% confidence interval [CI]: 11% to 34%), 11%
      in RSV testing (95% CI: 6% to 17%), 7% in albuterol use (95% CI: 0.2% to 13%),
      and 41 minutes in ED LOS (95% CI: 16 to 65 minutes). Mean cost per patient was
      reduced by $197 (95% CI: $136 to $259). Total cost savings was $196,409 (95% CI:
      $135,592 to $258,223) over the 2 bronchiolitis seasons after guideline
      implementation. There were no significant differences in antibiotic use,
      admission rates, or returns resulting in admission within 72 hours of discharge.
      CONCLUSIONS: A bronchiolitis guideline was associated with reductions in CXR, RSV
      testing, albuterol use, ED LOS, and total costs in a pediatric ED.

PMID- 24324001
TI  - Comparative effectiveness of empiric antibiotics for community-acquired
      pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Narrow-spectrum antibiotics are recommended as the
      first-line agent for children hospitalized with community-acquired pneumonia
      (CAP). There is little scientific evidence to support that this consensus-based
      recommendation is as effective as the more commonly used broad-spectrum
      antibiotics. The objective was to compare the effectiveness of empiric treatment
      with narrow-spectrum therapy versus broad-spectrum therapy for children
      hospitalized with uncomplicated CAP. METHODS: This multicenter retrospective
      cohort study using medical records included children aged 2 months to 18 years at
      4 children's hospitals in 2010 with a discharge diagnosis of CAP. Patients
      receiving either narrow-spectrum or broad-spectrum therapy in the first 2 days of
      hospitalization were eligible. Patients were matched by using propensity scores
      that determined each patient's likelihood of receiving empiric narrow or broad
      coverage. A multivariate logistic regression analysis evaluated the relationship
      between antibiotic and hospital length of stay (LOS), 7-day readmission,
      standardized daily costs, duration of fever, and duration of supplemental oxygen.
      RESULTS: Among 492 patients, 52% were empirically treated with a narrow-spectrum
      agent and 48% with a broad-spectrum agent. In the adjusted analysis, the narrow
      spectrum group had a 10-hour shorter LOS (P = .04). There was no significant
      difference in duration of oxygen, duration of fever, or readmission. When modeled
      for LOS, there was no difference in average daily standardized cost (P = .62) or
      average daily standardized pharmacy cost (P = .26). CONCLUSIONS: Compared with
      broad-spectrum agents, narrow-spectrum antibiotic coverage is associated with
      similar outcomes. Our findings support national consensus recommendations for the
      use of narrow-spectrum antibiotics in children hospitalized with CAP.

PMID- 24324002
TI  - Early puberty, negative peer influence, and problem behaviors in adolescent
      girls.
AB  - OBJECTIVE: To determine how early puberty and peer deviance relate to
      trajectories of aggressive and delinquent behavior in early adolescence and
      whether these relationships differ by race/ethnicity. METHODS: In this
      longitudinal study, 2607 girls from 3 metropolitan areas and their parents were
      interviewed at ages 11, 13, and 16 years. Girls reported on their age of onset of
      menarche, best friend's deviant behavior, delinquency, and physical, relational,
      and nonphysical aggression. Parents provided information on family
      sociodemographic characteristics and girls' race/ethnicity. RESULTS: Sixteen
      percent of girls were classified as early maturers (defined by onset of menarche
      before age 11 years). Overall, relational and nonphysical aggression increased
      from age 11 to age 16, whereas delinquency and physical aggression remained
      stable. Early puberty was associated with elevated delinquency and physical
      aggression at age 11. The relationship with early puberty diminished over time
      for physical aggression but not for delinquency. Best friend's deviant behavior
      was linked with higher levels of all problem behaviors, but the effect lessened
      over time for most outcomes. Early puberty was associated with a stronger link
      between best friend's deviance and delinquency, suggesting increased
      vulnerability to negative peer influences among early-maturing girls. A similar
      vulnerability was observed for relational and nonphysical aggression among girls
      in the "other" racial/ethnic minority group only. CONCLUSIONS: Early puberty and
      friends' deviance may increase the risk of problem behavior in young adolescent
      girls. Although many of these associations dissipate over time, early-maturing
      girls are at risk of persistently higher delinquency and stronger negative peer
      influences.

PMID- 24324003
TI  - Morphological, biophysical and synaptic properties of glutamatergic neurons of
      the mouse spinal dorsal horn.
AB  - Interneurons of the spinal dorsal horn are central to somatosensory and
      nociceptive processing. A mechanistic understanding of their function depends on
      profound knowledge of their intrinsic properties and their integration into
      dorsal horn circuits. Here, we have used BAC transgenic mice expressing enhanced
      green fluorescent protein (eGFP) under the control of the vesicular glutamate
      transporter (vGluT2) gene (vGluT2::eGFP mice) to perform a detailed
      electrophysiological and morphological characterisation of excitatory dorsal horn
      neurons, and to compare their properties to those of GABAergic (Gad67::eGFP
      tagged) and glycinergic (GlyT2::eGFP tagged) neurons. vGluT2::eGFP was detected
      in about one-third of all excitatory dorsal horn neurons and, as demonstrated by
      the co-expression of vGluT2::eGFP with different markers of subtypes of
      glutamatergic neurons, probably labelled a representative fraction of these
      neurons. Three types of dendritic tree morphologies (vertical, central, and
      radial), but no islet cell-type morphology, were identified in vGluT2::eGFP
      neurons. vGluT2::eGFP neurons had more depolarised action potential thresholds
      and longer action potential durations than inhibitory neurons, while no
      significant differences were found for the resting membrane potential, input
      resistance, cell capacitance and after-hyperpolarisation. Delayed firing and
      single action potential firing were the single most prevalent firing patterns in
      vGluT2::eGFP neurons of the superficial and deep dorsal horn, respectively. By
      contrast, tonic firing prevailed in inhibitory interneurons of the dorsal horn.
      Capsaicin-induced synaptic inputs were detected in about half of the excitatory
      and inhibitory neurons, and occurred more frequently in superficial than in deep
      dorsal horn neurons. Primary afferent-evoked (polysynaptic) inhibitory inputs
      were found in the majority of glutamatergic and glycinergic neurons, but only in
      less than half of the GABAergic population. Excitatory dorsal horn neurons thus
      differ from their inhibitory counterparts in several biophysical properties and
      possibly also in their integration into the local neuronal circuitry.

PMID- 24324005
TI  - Unmasking the open secret of posting and transfer practices in the health sector.
AB  - This article focuses on processes of granting posts and transfers to health care
      workers and administrators that can be described as 'mission inconsistent (MI)',
      meaning that they are not conducted in a way that maximizes health outcomes or
      that respects the norms of health care worker professionalism. We synthesize
      relevant literature from several different disciplinary perspectives to describe
      what is known about the problem of MI posting and transfer in the health sector,
      to critically engage and interrogate these literatures, and to briefly discuss
      efforts that have been made to maximize mission consistency. The article
      concludes by suggesting principles for future research that would foster a more
      complete understanding of posting and transfer practices. 

PMID- 24324004
TI  - Conduit artery structure and function in lowlanders and native highlanders:
      relationships with oxidative stress and role of sympathoexcitation.
AB  - Research detailing the normal vascular adaptions to high altitude is minimal and
      often confounded by pathology (e.g., chronic mountain sickness) and
      methodological issues. We examined vascular function and structure in: (1)
      healthy lowlanders during acute hypoxia and prolonged (~2 weeks) exposure to high
      altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy
      lowlanders (aged 32 +/- 7 years) and 12 highlanders (Sherpa; 33 +/- 14 years) we
      assessed brachial endothelium-dependent flow-mediated dilatation (FMD),
      endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid
      intima-media thickness (CIMT) and diameter (ultrasound), and arterial stiffness
      via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers
      of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite
      (NO2-) and lipid soluble antioxidants were also obtained at rest. In lowlanders,
      measurements were performed at sea level (334 m) and between days 3-4 (acute high
      altitude) and 12-14 (chronic high altitude) following arrival to 5050 m.
      Highlanders were assessed once at 5050 m. Compared with sea level, acute high
      altitude reduced lowlanders' FMD (7.9 +/- 0.4 vs. 6.8 +/- 0.4%; P = 0.004) and
      GTN-induced dilatation (16.6 +/- 0.9 vs. 14.5 +/- 0.8%; P = 0.006), and raised
      central PWV (6.0 +/- 0.2 vs. 6.6 +/- 0.3 m s(-1); P = 0.001). These changes
      persisted at days 12-14, and after allometrically scaling FMD to adjust for
      altered baseline diameter. Compared to lowlanders at sea level and high altitude,
      highlanders had a lower carotid wall:lumen ratio (~19%, P <= 0.04), attributable
      to a narrower CIMT and wider lumen. Although both LOOH and NO2- increased with
      high altitude in lowlanders, only LOOH correlated with the reduction in GTN
      induced dilatation evident during acute (n = 11, r = -0.53) and chronic (n = 7, r
      = -0.69; P <= 0.01) exposure to 5050 m. In a follow-up, placebo-controlled
      experiment (n = 11 healthy lowlanders) conducted in a normobaric hypoxic chamber
      (inspired O2 fraction (F IO 2) = 0.11; 6 h), a sustained reduction in FMD was
      evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7 +/
      1.6 vs. 8.0 +/-1.3%; P < 0.01); this decline in FMD was largely reversed
      following alpha1-adrenoreceptor blockade. In conclusion, high-altitude exposure
      in lowlanders caused persistent impairment in vascular function, which was
      mediated partially via oxidative stress and sympathoexcitation. Although a
      lifetime of high-altitude exposure neither intensifies nor attenuates the
      impairments seen with short-term exposure, chronic high-altitude exposure appears
      to be associated with arterial remodelling.

PMID- 24324006
TI  - The Cryptococcus neoformans Rim101 transcription factor directly regulates genes
      required for adaptation to the host.
AB  - The Rim101 protein is a conserved pH-responsive transcription factor that
      mediates important interactions between several fungal pathogens and the infected
      host. In the human fungal pathogen Cryptococcus neoformans, the Rim101 protein
      retains conserved functions to allow the microorganism to respond to changes in
      pH and other host stresses. This coordinated cellular response enables this
      fungus to effectively evade the host immune response. Preliminary studies suggest
      that this conserved transcription factor is uniquely regulated in C. neoformans
      both by the canonical pH-sensing pathway and by the cyclic AMP (cAMP)/protein
      kinase A (PKA) pathway. Here we present comparative transcriptional data that
      demonstrate a strong concordance between the downstream effectors of PKA and
      Rim101. To define Rim101-dependent gene expression during a murine lung
      infection, we used nanoString profiling of lung tissue infected with a wild-type
      or rim101Delta mutant strain. In this setting, we demonstrated that Rim101
      controls the expression of multiple cell wall-biosynthetic genes, likely
      explaining the enhanced immunogenicity of the rim101Delta mutant. Despite its
      divergent upstream regulation, the C. neoformans Rim101 protein recognizes a
      conserved DNA binding motif. Using these data, we identified direct targets of
      this transcription factor, including genes involved in cell wall regulation.
      Therefore, the Rim101 protein directly controls cell wall changes required for
      the adaptation of C. neoformans to its host environment. Moreover, we propose
      that integration of the cAMP/PKA and pH-sensing pathways allows C. neoformans to
      respond to a broad range of host-specific signals. 

PMID- 24324007
TI  - Context-dependent enhancer selection confers alternate modes of notch regulation
      on argos.
AB  - Wiring between signaling pathways differs according to context, as exemplified by
      interactions between Notch and epidermal growth factor receptor (EGFR) pathways,
      which are cooperative in some contexts but antagonistic in others. To investigate
      mechanisms that underlie different modes of cross talk, we have focused on argos,
      an EGFR pathway regulator in Drosophila melanogaster which is upregulated by
      Notch in adult muscle progenitors but is repressed in the wing. Results show that
      the alternate modes of cross talk depend on the engagement of enhancers with
      opposite regulatory logic, which are selected by context-determining factors.
      This is likely to be a general mechanism for enabling the wiring between these
      pathways to switch according to context. 

PMID- 24324008
TI  - Distinct functions of human cohesin-SA1 and cohesin-SA2 in double-strand break
      repair.
AB  - Cohesin is an essential multiprotein complex that mediates sister chromatid
      cohesion critical for proper segregation of chromosomes during cell division.
      Cohesin is also involved in DNA double-strand break (DSB) repair. In mammalian
      cells, cohesin is involved in both DSB repair and the damage checkpoint response,
      although the relationship between these two functions is unclear. Two cohesins
      differing by one subunit (SA1 or SA2) are present in somatic cells, but their
      functional specificities with regard to DNA repair remain enigmatic. We found
      that cohesin-SA2 is the main complex corecruited with the cohesin-loading factor
      NIPBL to DNA damage sites in an S/G(2)-phase-specific manner. Replacing the
      diverged C-terminal region of SA1 with the corresponding region of SA2 confers
      this activity on SA1. Depletion of SA2 but not SA1 decreased sister chromatid
      homologous recombination repair and affected repair pathway choice, indicating
      that DNA repair activity is specifically associated with cohesin recruited to
      damage sites. In contrast, both cohesin complexes function in the intra-S
      checkpoint, indicating that cell cycle-specific damage site accumulation is not a
      prerequisite for cohesin's intra-S checkpoint function. Our findings reveal the
      unique ways in which cohesin-SA1 and cohesin-SA2 participate in the DNA damage
      response, coordinately protecting genome integrity in human cells.

PMID- 24324009
TI  - SirT3 regulates the mitochondrial unfolded protein response.
AB  - The mitochondria of cancer cells are characterized by elevated oxidative stress
      caused by reactive oxygen species (ROS). Such an elevation in ROS levels
      contributes to mitochondrial reprogramming and malignant transformation. However,
      high levels of ROS can cause irreversible damage to proteins, leading to their
      misfolding, mitochondrial stress, and ultimately cell death. Therefore,
      mechanisms to overcome mitochondrial stress are needed. The unfolded protein
      response (UPR) triggered by accumulation of misfolded proteins in the
      mitochondria (UPR(mt)) has been reported recently. So far, the UPR(mt) has been
      reported to involve the activation of CHOP and estrogen receptor alpha (ERalpha).
      The current study describes a novel role of the mitochondrial deacetylase SirT3
      in the UPR(mt). Our data reveal that SirT3 acts to orchestrate two pathways, the
      antioxidant machinery and mitophagy. Inhibition of SirT3 in cells undergoing
      proteotoxic stress severely impairs the mitochondrial network and results in
      cellular death. These observations suggest that SirT3 acts to sort moderately
      stressed from irreversibly damaged organelles. Since SirT3 is reported to act as
      a tumor suppressor during transformation, our findings reveal a dual role of
      SirT3. This novel role of SirT3 in established tumors represents an essential
      mechanism of adaptation of cancer cells to proteotoxic and mitochondrial stress. 

PMID- 24324010
TI  - Genotoxic stress prevents Ndd1-dependent transcriptional activation of G2/M
      specific genes in Saccharomyces cerevisiae.
AB  - Downregulation of specific transcripts is one of the mechanisms utilized by
      eukaryotic checkpoint systems to prevent cell cycle progression. Here we
      identified and explored such a mechanism in the yeast Saccharomyces cerevisiae.
      It involves the Mec1-Rad53 kinase cascade, which attenuates G(2)/M-specific gene
      transcription upon genotoxic stress. This inhibition is achieved via multiple
      Rad53-dependent inhibitory phosphorylations on the transcriptional activator Ndd1
      that prevent its chromatin recruitment via interactions with the forkhead factor
      Fkh2. Relevant modification sites on Ndd1 were identified by mass spectrometry,
      and corresponding alanine substitutions were able to suppress a methyl
      methanesulfonate-induced block in Ndd1 chromatin recruitment. Whereas effective
      suppression by these Ndd1 mutants is achieved for DNA damage, this is not the
      case under replication stress conditions, suggesting that additional mechanisms
      must operate under such conditions. We propose that budding yeast cells prevent
      the normal transcription of G(2)/M-specific genes upon genotoxic stress to
      precisely coordinate the timing of mitotic and postmitotic events with respect to
      S phase.

PMID- 24324012
TI  - Canada in breach of ethical standards for clinical trials.

PMID- 24324014
TI  - A 28-year-old military veteran with nightmares and insomnia.

PMID- 24324011
TI  - Rad53 downregulates mitotic gene transcription by inhibiting the transcriptional
      activator Ndd1.
AB  - The 33 genes in the Saccharomyces cerevisiae mitotic CLB2 transcription cluster
      have been known to be downregulated by the DNA damage checkpoint for many years.
      Here, we show that this is mediated by the checkpoint kinase Rad53 and the
      dedicated transcriptional activator of the cluster, Ndd1. Ndd1 is phosphorylated
      in response to DNA damage, which blocks recruitment to promoters and leads to the
      transcriptional downregulation of the CLB2 cluster. Finally, we show that
      downregulation of Ndd1 is an essential function of Rad53, as a hypomorphic ndd1
      allele rescues RAD53 deletion. 

PMID- 24324015
TI  - Medical interventions to reduce motor vehicle collisions.

PMID- 24324016
TI  - Health worker-only HIV clinic improves care for all.

PMID- 24324017
TI  - Low-risk snip may help tongue-tied infants breastfeed.

PMID- 24324018
TI  - Reducing missed orthopedic injuries in the ER.

PMID- 24324019
TI  - Bilateral central scotomas following laser pointer misuse.

PMID- 24324021
TI  - The hidden curriculum.

PMID- 24324020
TI  - Noninvasive ventilation as a weaning strategy for mechanical ventilation in
      adults with respiratory failure: a Cochrane systematic review.
AB  - BACKGROUND: Noninvasive ventilation has been studied as a means of reducing
      complications among patients being weaned from invasive mechanical ventilation.
      We sought to summarize evidence comparing noninvasive and invasive weaning and
      their effects on mortality. METHODS: We identified relevant randomized and
      quasirandomized trials through searches of databases, conference proceedings and
      grey literature. We included trials comparing extubation and immediate
      application of noninvasive ventilation with continued invasive weaning in adults
      on mechanical ventilation. Two reviewers each independently screened citations,
      assessed trial quality and abstracted data. Our primary outcome was mortality.
      RESULTS: We identified 16 trials involving 994 participants, most of whom had
      chronic obstructive pulmonary disease (COPD). Compared with invasive weaning,
      noninvasive weaning significantly reduced mortality (risk ratio [RR] 0.53, 95%
      confidence interval [CI] 0.36 to 0.80), weaning failures (RR 0.63, 95% CI 0.42 to
      0.96), ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to 0.43), length of
      stay in the intensive care unit (mean difference [MD] -5.59 d, 95% CI -7.90 to 
      3.28) and in hospital (MD -6.04 d, 95% CI -9.22 to -2.87), and total duration of
      mechanical ventilation (MD -5.64 d, 95% CI -9.50 to -1.77). Noninvasive weaning
      had no significant effect on the duration of ventilation related to weaning, but
      significantly reduced rates of tracheostomy (RR 0.19, 95% CI 0.08 to 0.47) and
      reintubation (RR 0.65, 95% CI 0.44 to 0.97). Mortality benefits were
      significantly greater in trials enrolling patients with COPD than in trials
      enrolling mixed patient populations (RR 0.36 [95% CI 0.24 to 0.56] v. RR 0.81
      [95% CI 0.47 to 1.40]). INTERPRETATION: Noninvasive weaning reduces rates of
      death and pneumonia without increasing the risk of weaning failure or
      reintubation. In subgroup analyses, mortality benefits were significantly greater
      in patients with COPD.

PMID- 24324023
TI  - Plan B emergency contraceptive may be ineffective for heavier women.

PMID- 24324024
TI  - Comment on Levy's 'Forced to be free? Increasing patient autonomy by constraining
      it'.

PMID- 24324025
TI  - The impact of self-reported oligo-amenorrhea and hirsutism on fertility and
      lifetime reproductive success: results from the Northern Finland Birth Cohort
      1966.
AB  - STUDY QUESTION: To what extent do self-reported oligo-amenorrhea and hirsutism
      affect reproductive performance (childlessness, age at first delivery, family
      size and miscarriage rates)? SUMMARY ANSWER: At the age of 44, among women with
      both self-reported oligo-amenorrhea and hirsutism the prevalence of childlessness
      was not significantly different from non-symptomatic women but they had a smaller
      family size than non-symptomatic women. WHAT IS KNOWN ALREADY: Polycystic ovary
      syndrome (PCOS) is a common endocrine disorder characterized by oligo-amenorrhea
      or amenorrhea, hyperandrogenism and hirsutism and it is the most frequent cause
      of anovulatory infertility, but there are few studies on the reproductive
      capacity of women with PCOS. In our previous population-based cohort study the
      women with self-reported oligo-amenorrhea and hirsutism were found to have more
      infertility problems and smaller family size than non-symptomatic women at the
      age of 31. STUDY DESIGN, SIZE, DURATION: A prospective population-based cohort
      study. The population of the study is derived from the prospective Northern
      Finland Birth Cohort 1966 (NFBC1966), comprising all expected births from the
      year 1966 in the two northernmost provinces of Finland (n = 12 058). Of them,
      5889 were females. Enrollment in this database begun at the 24th gestational week
      and so far data have been collected from the subjects at the ages of 1, 14 and 31
      years. PARTICIPANTS/MATERIALS, SETTING, METHODS: A postal questionnaire including
      questions about oligo-amenorrhea and hirsutism was sent to all women at the age
      of 31 (n = 5608, response rate 81%, n = 4535) and a clinical examination was
      performed (attendance rate 76.5%). Those who reported both hirsutism and oligo
      amenorrhea were defined as women with both symptoms (n = 153). Data on
      pregnancies/deliveries were obtained from the Finnish Medical Birth Register
      (FMBR) in 2010 when the women were 44 years old. MAIN RESULTS AND THE ROLE OF
      CHANCE: Women with both symptoms had delivered at least one child as often as non
      symptomatic women [75.2 versus 79.0%, adjusted odds ratio (OR) 0.86, 95%
      confidence intervals (CI) 0.57-1.30], were of similar age [mean (SD)] at first
      delivery [27.7 (4.81) versus 27.3 (4.71)] and had similar incidence of
      miscarriages. However, non-symptomatic women had more often >=2 deliveries (61.6
      versus 52.9%, adjusted OR 0.70, 95% CI 0.49-1.00, P = 0.048) and had larger
      family size [mean (SD)] [2.4 (1.4) versus 1.9 (0.8), P < 0.001]. Women with both
      symptoms had been treated more often for infertility than non-symptomatic women
      (6.1 versus 2.4%, adjusted OR 2.74, 95% CI 1.14-6.60, P = 0.024). LIMITATIONS,
      REASONS FOR CAUTION: The diagnosis of oligo-amenorrhea and hirsutism was based on
      a questionnaire, suggesting a risk of information bias in reporting the symptoms.
      However, we have previously shown that self-reported oligo-amenorrhea and
      hirsutism can distinguish most women with the typical profile of PCOS. Only the
      women who had delivered at least once were recorded in the FMBR, thus excluding
      from the study those who had experienced miscarriages and/or infertility
      treatments but did not have a live birth. This feature could potentially decrease
      the differences in incidence of miscarriages and/or infertility treatment between
      symptomatic and non-symptomatic subjects. WIDER IMPLICATIONS OF THE FINDINGS:
      This is one of the few studies, in which the impact of self-reported oligo
      amenorrhea and hirsutism on lifetime reproductive success can be measured. Our
      results suggest that even at more advanced age, women with both symptoms do not
      quite match the parity of healthy non-symptomatic women, and that infertility
      treatment does not always restore normal reproductive capacity in these women.
      Obese women with both symptoms had the worst prognostic as regards reproduction,
      which emphasizes the importance of life intervention and preventive politics
      against obesity in this group of women. STUDY FUNDING/COMPETING INTEREST(S): This
      work was supported by grants from the Finnish Medical Society Duodecim, the North
      Ostrobothnia Regional Fund, the Academy of Finland, University Hospital Oulu,
      Biocenter, University of Oulu, Finland, the European Commission and the Medical
      Research Council, UK, the National Institute for Health Research (NIHR). None of
      the authors has any conflict of interest to declare.

PMID- 24324026
TI  - Effects of embryo culture media do not persist after implantation: a histological
      study in mice.
AB  - STUDY QUESTION: Is post-implantation embryonic development after blastocyst
      transfer affected by exposure to different assisted reproduction technology (ART)
      culture media? SUMMARY ANSWER: Fetal development and placental histology of ART
      embryos cultured in vitro in different ART media was not impaired compared with
      embryos grown in vivo. WHAT IS KNOWN ALREADY: The application of different in
      vitro culture (IVC) media for human ART has an effect on birthweight of newborns.
      In the mouse model, differences in blastocyst formation were reported after
      culture in different ART media. Moreover, abnormalities in the liver and heart
      have been detected as a result of suboptimal IVC conditions. STUDY DESIGN, SIZE,
      DURATION: Fertilized oocytes from inbred and outbred breeding schemes were
      retrieved and either immediately transferred to foster mothers or incubated in
      control or human ART culture media up to the blastocyst stage prior to transfer.
      Placental and fetal anatomy and particularly bone development were evaluated.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: B6C3F1 female mice were used as oocyte
      donors after ovulation induction. C57Bl/6 and CD1 males were used for mating and
      CD1 females as foster mothers for embryo transfer. Fertilized oocytes were
      recovered from mated females and incubated in sequential human ART media
      (ISM1/ISM2 and HTF/Multiblast), in control media [KSOM(aa) and Whitten's medium]
      or grown in utero without IVC (zygote control). As in vivo, control B6C3F1
      females were superovulated and left untreated. Fetuses and placentae were
      isolated by Caesarean section and analysed at 18.5 days post-coitum (dpc) for
      placenta composition and at 15.5 dpc for body weight, crown-rump length (CRL),
      fetal organ development, morphological development, total bone length and extent
      of bone ossification. MAIN RESULTS AND THE ROLE OF CHANCE: No major differences
      in the number of implantation sites or in histological appearance of the
      placentae were detected. CRL of KSOM(aa) fetuses was higher compared with zygote
      control and Whitten's medium. Histological analysis of tissue sections revealed
      no gross morphological differences compared with the in vitro groups or in vivo
      controls. Furthermore, no changes in skeletal development and degree of
      ossification were observed. However, fibula and tibia of ISM1/ISM2 fetuses were
      longer than the respective ones from in vivo fetuses. LIMITATIONS, REASONS FOR
      CAUTION: Findings in the mouse embryo and fetus may not be fully transferable to
      humans. In addition to skeletal development and placentation, there may be other
      parameters, e.g. on the molecular level which respond to IVC in ART media. Some
      comparisons have limited statistical power. WIDER IMPLICATIONS OF THE FINDINGS:
      Our data suggest that once implantation is achieved, subsequent post-implantation
      development unfolds normally, resulting in healthy fetuses. With mouse models, we
      gather information for the safety of human ART culture media. Our mouse study is
      reassuring for the safety of ART conditions on human embryonic development, given
      the lack of bold detrimental effects observed in the mouse model. STUDY
      FUNDING/COMPETING INTEREST(S): This work was supported by the Deutsche
      Forschungsgemeinschaft (BO 2540/4-1 and SCHL 394/9-1) and by the Nederlandse
      Organisatie voor Wetenschappelijk Onderzoek (S.L.G.); Bilateral grant NWO-DFG 63
      258. None of the authors has any conflict of interest to declare. TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 24324028
TI  - Brucella ceti from two striped dolphins stranded on the Apulia coastline, Italy.
AB  - Since 1994, when Brucella ceti was first isolated from an aborted dolphin fetus,
      several cases have been reported worldwide. The first case of B. ceti in the
      Mediterranean (and in Italy), however, was recorded only in 2012, off the coast
      of Tuscany. Extensive studies, using serological and microbiological methods,
      have documented this bacterium in dolphins and demonstrated its zoonotic
      potential. We describe the typing of two B. ceti strains isolated from striped
      dolphins (Stenella coeruleoalba) stranded on the southern Apulia coastline. B.
      ceti isolates were conventionally typed, and then genotyped by both the
      multilocus sequence typing (MLST) and the multilocus variable number of tandem
      repeats typing (MLVA) methodologies to infer phylogeny and potential
      epidemiological links between the two cases. The two isolates were identified
      through MLST analysis as belonging to the common sequence type 26 (ST26), while
      MLVA analysis, having established that the two isolates have identical profiles,
      assigned them to a novel genotype within cluster A - a unique representative of a
      new Mediterranean subcluster. The results thus revealed a link between the two
      cases studied, demonstrating the usefulness of MLST and MLVA for the
      epidemiological investigation of brucellae among marine mammals. 

PMID- 24324027
TI  - Gene dosage as a relevant mechanism contributing to the determination of ovarian
      function in Turner syndrome.
AB  - STUDY QUESTION: What is the burden of X chromosome mosaicism in the occurrence of
      spontaneous menarche (SM) in Turner syndrome (TS)? SUMMARY ANSWER: SM was
      significantly associated with X chromosome mosaicism in the TS patients; a
      mosaicism with around 10% euploid cell line may predict spontaneous pubertal
      development when determined by molecular-cytogenetic techniques on uncultivated
      tissues. WHAT IS KNOWN ALREADY: Spontaneous puberty can be observed in a minority
      of patients with TS, more frequently, but not exclusively, in those with a high
      level of 46,XX/45,X mosaicism at standard karyotype. The genetic mechanisms
      contributing to ovarian function in TS patients are still not determined.
      However, submicroscopic X-linked and autosomal copy number variations (CNVs) have
      recently emerged as an important genetic risk category for premature ovarian
      insufficiency and may be involved in modulating the TS ovarian phenotype. STUDY
      DESIGN, SIZE, DURATION: A group of 40 patients with a diagnosis of TS at
      conventional karyotyping participated in the study; 6 patients had SM and 34
      patients had primary amenorrhoea (PA). All clinical data and the patients' DNA
      samples were collected over the years at a single paediatric clinic.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients' samples were used to
      perform both genetic (Copy Number Assay) and molecular-cytogenetic (array-CGH and
      iFISH, interphase-FISH) analyses in order to evaluate the X chromosome mosaicism
      rate and to detect possible rare CNVs of genes with a known or predicted role in
      female fertility. MAIN RESULTS AND THE ROLE OF CHANCE: All TS patients showed
      variable percentages of the 46,XX lineage, but these percentages were higher in
      the SM group (P < 0.01). A mosaicism around 10% for the euploid cell line may
      predict spontaneous pubertal development when determined by molecular-cytogenetic
      techniques performed in uncultivated tissues. A few CNVs involving autosomal and
      X-linked ovary-related loci were identified by array-CGH analysis and confirmed
      by real-time quantitative PCR, including a BMP15 gene duplication at Xp11.22, a
      deletion interrupting the PAPPA gene at 9q33.1, and an intragenic duplication
      involving the PDE8A gene at 15q25.3. LIMITATIONS, REASONS FOR CAUTION: This is a
      pilot study on a relatively small sample size and confirmation in larger TS
      cohorts may be required. The ovarian tissue could not be studied in any patients
      and in a subgroup of patients, the mosaicism was estimated in tissues of
      different embryonic origin. WIDER IMPLICATIONS OF THE FINDINGS: The combined
      determination of X chromosome mosaicism by molecular and molecular-cytogenetic
      techniques may become useful for the prediction of SM in TS. The detection of
      CNVs in both X-linked and autosomal ovary-related genes further suggests gene
      dosage as a relevant mechanism contributing to the ovarian phenotype of TS
      patients. These CNVs may pinpoint novel candidates relevant to female fertility
      and generate further insights into the mechanisms contributing to ovarian
      function. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Telethon
      Foundation (grant no: GGP09126 to L.P.), the Italian Ministry of the University
      and Research (grant number: 2006065999 to P.F.) and a Ministry of Health grant
      'Ricerca Corrente' to IRCCS Istituto Auxologico Italiano (grant number: 08C704
      2006). The authors have no conflict of interest to declare.

PMID- 24324029
TI  - Emerging Chlamydia psittaci infections in chickens and examination of
      transmission to humans.
AB  - Chlamydia psittaci and atypical Chlamydiaceae infections are (re)-emerging in
      chickens. We therefore examined the prevalence of C. psittaci, atypical
      Chlamydiaceae and their zoonotic transmission on 19 Belgian chicken farms.
      Atypical Chlamydiaceae were not detected in chickens but 18 out of 19 farms were
      positive for C. psittaci by culture and PCR. C. psittaci ompA genotypes A and D
      were discovered. None of the examined humans (n = 31) was infected with atypical
      Chlamydiaceae, but 29 (93.5%) of them were positive for C. psittaci by culture
      and PCR. Genotypes A, D and a mixed infection with genotypes C and D were found.
      Humans (n = 2) working at the C. psittaci-negative farm never had respiratory
      complaints, while 25 out of 29 positive farmers (86.2%) reported yearly medical
      complaints potentially related to psittacosis. Four of them currently experienced
      respiratory disease and one of them was being treated with antibiotics. Four
      farmers (12.5%) mentioned that they had pneumonia after starting to keep
      chickens. Occupational physicians should be aware of emerging Chlamydiaceae
      infections in chickens.

PMID- 24324030
TI  - Detection of enterovirus 68 as one of the commonest types of enterovirus found in
      patients with acute respiratory tract infection in China.
AB  - Human enterovirus 68 (HEV-68) is an enterovirus associated with respiratory
      illness. In China, no information about HEV-68 is available for children yet.
      This study aimed to investigate the presence of HEV-68 in mainland China between
      2009 and 2012 and to explore the migration events of HEV-68 across the world.
      Among 1565 samples tested from children, 41 (2.6%) were positive for HEV and 223
      (14.3%) for human rhinovirus (HRV). Seven (17.1%) of 41 HEVs were HEV-68. Two HEV
      68- and five HRV-positive samples were detected in 585 adult samples. HEV-68 is
      the predominant type of enterovirus in children with acute respiratory tract
      infection (ARTI), followed by HEV-71 and coxsackievirus A6. Three HEV-68-infected
      children presented with severe pneumonia and one presented with a severe asthma
      attack. The viruses were attributed to two novel distinct sublineages of HEV-68
      based on phylogenetic analysis of partial VP1 gene sequences. Migration events
      analysis showed that the USA and the Netherlands were possible geographical
      sources of HEV-68, from where three strains migrated to China. In conclusion, HEV
      68 may play a predominant role among the enteroviruses associated with ARTI in
      children. Additional surveillance is needed to clarify the reason why HEV-68
      causes such a wide spectrum of disease, from asymptomatic to severe respiratory
      disease and even death.

PMID- 24324031
TI  - .Analysis of the contribution of bacteriophage ST64B to in vitro virulence traits
      of Salmonella enterica serovar Typhimurium.
AB  - Comparison of the publicly available genomes of the virulent Salmonella enterica
      serovar Typhimurium (S. Typhimurium) strains SL1344, 14028s and D23580 to that of
      the virulence-attenuated isolate LT2 revealed the absence of a full sequence of
      bacteriophage ST64B in the latter. Four selected ST64B regions of unknown
      function (sb7-sb11, sb46, sb49-sb50 and sb54) were mapped by PCR in two strain
      collections: (i) 310 isolates of S. Typhimurium from human blood or stool
      samples, and from food, animal and environmental reservoirs; and (ii) 90 isolates
      belonging to other serovars. The region sb49-sb50 was found to be unique to S.
      Typhimurium and was strongly associated with strains isolated from blood samples
      (100  and 28.4 % of the blood and non-blood isolates, respectively). The region
      was cloned into LT2 and knocked out in SL1344, and these strains were compared to
      wild-type isogenic strains in in vitro assays used to predict virulence
      association. No difference in invasion of the Int407 human cell line was observed
      between the wild-type and mutated strains, but the isolate carrying the whole
      ST64B prophage was found to have a slightly better survival in blood. The study
      showed a high prevalence and a strong association between the prophage ST64B and
      isolates of S. Typhimurium collected from blood, and may indicate that such
      strains constitute a selected subpopulation within this serovar. Further studies
      are indicated to determine whether the slight increase in blood survival observed
      in the strain carrying ST64B genes is of paramount importance for systemic
      infections. 

PMID- 24324032
TI  - Single-cell genomics reveals metabolic strategies for microbial growth and
      survival in an oligotrophic aquifer.
AB  - Bacteria from the genus Pedobacter are a major component of microbial assemblages
      at Hanford Site (a largely decommissioned nuclear production complex) in eastern
      Washington state, USA, and have been shown to change significantly in abundance
      in response to the subsurface intrusion of Columbia River water. Here we employed
      single-cell genomics techniques to shed light on the physiological niche of these
      micro-organisms. Analysis of four Pedobacter single amplified genomes (SAGs) from
      Hanford Site sediments revealed a chemoheterotrophic lifestyle, with the
      potential to exist under both aerobic and microaerophilic conditions via
      expression of both aa3-type and cbb3-type cytochrome c oxidases. These SAGs
      encoded a wide range of both intra- and extracellular carbohydrate-active
      enzymes, potentially enabling the degradation of recalcitrant substrates such as
      xylan and chitin, and the utilization of more labile sugars such as mannose and
      fucose. Coupled to these enzymes, a diversity of transporters and sugar-binding
      molecules were involved in the uptake of carbon from the extracellular local
      environment. The SAGs were enriched in TonB-dependent receptors, which play a key
      role in uptake of substrates resulting from degradation of recalcitrant carbon.
      Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas mechanisms
      for resisting viral infections were identified in all SAGs. These data
      demonstrate the potential mechanisms utilized for persistence by heterotrophic
      micro-organisms in a carbon-limited aquifer, and hint at potential linkages
      between observed Pedobacter abundance shifts within the 300 Area (in the south
      eastern corner of the site) subsurface and biogeochemical shifts associated with
      Columbia River water intrusion. 

PMID- 24324033
TI  - p53/mdm2 feedback loop sustains miR-221 expression and dictates the response to
      anticancer treatments in hepatocellular carcinoma.
AB  - The overexpression of microRNA-221 (miR-221) is reported in several human cancers
      including hepatocellular carcinoma, and its targeting by tailored treatments has
      been proposed. The evidence supporting the role of miR-221 in cancer is growing
      and has been mainly focused on the discovery of miR-221 targets as well as on its
      possible therapeutic exploitations. However, the mechanism sustaining miR-221
      aberrant expression remains to be elucidated. In this study, MDM2 (E3 ubiquitin
      protein ligase homolog), a known p53 (TP53) modulator, is identified as a direct
      target of miR-221, and a feed-forward loop is described that sustains miR-221
      aberrant expression. Interestingly, miR-221 can activate the p53/mdm2 axis by
      inhibiting MDM2 and, in turn, p53 activation contributes to miR-221 enhanced
      expression. Moreover, by modulating the p53 axis, miR-221 impacts cell-cycle
      progression and apoptotic response to doxorubicin in hepatocellular carcinoma
      derived cell lines. Finally, CpG island methylation status was assessed as a
      causative event associated with miR-221 upregulation in hepatocellular carcinoma
      cells and primary tumor specimens. In hepatocellular carcinoma-derived cell
      lines, pharmacologically induced DNA hypomethylation potentiated a significant
      increase in miR-221 expression. These data were confirmed in clinical specimens
      of hepatocellular carcinoma in which elevated miR-221 expression was associated
      with the simultaneous presence of wild-type p53 and DNA hypomethylation.
      IMPLICATIONS: These findings reveal a novel miR-221-sustained regulatory loop
      that determines a p53-context-specific response to doxorubicin treatment in
      hepatocellular carcinoma.

PMID- 24324034
TI  - Spermatogonial SOHLH1 nucleocytoplasmic shuttling associates with initiation of
      spermatogenesis in the rhesus monkey (Macaca mulatta).
AB  - As the spermatogenesis- and oogenesis-specific basic helix-loop-helix 1 (SOHLH1)
      transcription factor has been shown to be essential for spermatogonial
      differentiation in mice, we examined the immunoexpression of this protein in the
      testis of the rhesus monkey (Macaca mulatta) during puberty, the stage of
      development when spermatogonial differentiation is initiated in higher primates.
      Immunopositive SOHLH1 cells were observed only on the basement membrane of the
      seminiferous cords and tubules. Prior to puberty, essentially 100% of SOHLH1
      positive spermatogonia co-expressed the glial cell line-derived neurotrophic
      factor family receptor alpha 1 (GFRalpha1), a marker for undifferentiated
      spermatogonia, and >80% of the immunopositive SOHLH1 cells exhibited only
      cytoplasmic staining of this transcription factor. Nuclear-only SOHLH1 was found
      in <10% of spermatogonia in testes from pre-pubertal animals. Puberty was
      associated with a dramatic and progressive increase in the percentage of
      immunopositive SOHLH1 cells with nuclear-only staining, and this was associated
      with (i) a marked reduction in the fraction (~100-20%) of SOHLH1-positive germ
      cells co-expressing GFRalpha1 and (ii) a significant increase in the proportion
      of SOHLH1-positive spermatogonia that co-expressed the tyrosine kinase receptor
      (cKIT). Spermatogonia exhibiting nuclear SOHLH1 staining were found to be cKIT
      positive, but not all cKIT-positive spermatogonia exhibited nuclear SOHLH1
      staining. Taken together, these results suggest that, in the monkey, nuclear
      location of SOHLH1 is closely associated with spermatogonial differentiation. 

PMID- 24324035
TI  - Refractory hypertension: determination of prevalence, risk factors, and
      comorbidities in a large, population-based cohort.
AB  - Refractory hypertension is an extreme phenotype of antihypertensive treatment
      failure. Participants in the REasons for Geographic And Racial Differences in
      Stroke (REGARDS) Study, a large (n=30 239), population-based cohort were
      evaluated to determine the prevalence of refractory hypertension and associated
      cardiovascular risk factors and comorbidities. Refractory hypertension was
      defined as uncontrolled blood pressure (systolic/diastolic, >=140/90 mm Hg) on
      >=5 antihypertensive drug classes. Participants with resistant hypertension
      (systolic/diastolic, >=140/90 mm Hg on >=3 or <140/90 mm Hg on >=4
      antihypertensive classes) and all participants treated for hypertension served as
      comparator groups. Of 14 809 REGARDS participants receiving antihypertensive
      treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory
      hypertension was 3.6% among participants with resistant hypertension (n=2144) and
      41.7% among participants on >=5 antihypertensive drug classes. Among all
      participants with hypertension, black race, male sex, living in the stroke belt
      or buckle, higher body mass index, lower heart rate, reduced estimated glomerular
      filtration rate, albuminuria, diabetes mellitus, and history of stroke and
      coronary heart disease were associated with refractory hypertension. Compared
      with resistant hypertension, prevalence ratios for refractory hypertension were
      increased for blacks (3.00; 95% confidence interval, 1.68-5.37) and those with
      albuminuria (2.22; 95% confidence interval, 1.40-3.52) and diabetes mellitus
      (2.09; 95% confidence interval, 1.32-3.31). The median 10-year Framingham risk
      for coronary heart disease and stroke was higher among participants with
      refractory hypertension when compared with those with either comparator group.
      These data indicate that although resistant hypertension is relatively common
      among treated patients with hypertension, true antihypertensive treatment failure
      is rare. 

PMID- 24324036
TI  - Ambulatory pulse pressure: does it improve cardiovascular risk stratification?

PMID- 24324038
TI  - Office blood pressure, ambulatory blood pressure monitoring, and
      echocardiographic abnormalities in women with polycystic ovary syndrome: role of
      obesity and androgen excess.
AB  - Whether or not blood pressure (BP) and heart function of women with polycystic
      ovary syndrome (PCOS) are altered remains unclear, albeit subtle abnormalities in
      the regulation of BP observed in these women might suggest a mild masculinization
      of their cardiovascular system. To study the influence of obesity and androgen
      excess on BP and echocardiographic profiles of women with the syndrome, we
      conducted a cross-sectional case-control study comparing office and ambulatory BP
      monitoring, as well as echocardiographic assessments, in 63 premenopausal women
      with the classic phenotype, 33 nonhyperandrogenic women with regular menses, and
      25 young men. Forty-nine subjects were lean and 72 had weight excess (body mass
      index >=25 kg/m(2)). Participants had no previous history of hypertension and
      were nonsmokers. Men showed the highest BP readings, and the lowest readings were
      observed in control women, whereas women with PCOS had intermediate values.
      Undiagnosed hypertension was more common in subjects with weight excess
      irrespective of sex and hyperandrogenism. Women with PCOS and weight excess
      showed frequencies of previously undiagnosed hypertension that were similar to
      those of men with weight excess and higher than those observed in
      nonhyperandrogenic women. Lastly, male sex, weight excess and hypertension, the
      latter in men as well as in women with PCOS, increased left ventricular wall
      thickness. In summary, our results show that patients with classic PCOS and
      weight excess frequently have undiagnosed BP abnormalities, leading to target
      organ damage. 

PMID- 24324037
TI  - Ang II-salt hypertension depends on neuronal activity in the hypothalamic
      paraventricular nucleus but not on local actions of tumor necrosis factor-alpha.
AB  - Development of angiotensin II (Ang II)-dependent hypertension involves microglial
      activation and proinflammatory cytokine actions in the hypothalamic
      paraventricular nucleus (PVN). Cytokines activate receptor signaling pathways
      that can both acutely grade neuronal discharge and trigger long-term adaptive
      changes that modulate neuronal excitability through gene transcription. Here, we
      investigated contributions of PVN cytokines to maintenance of hypertension
      induced by subcutaneous infusion of Ang II (150 ng/kg per min) for 14 days in
      rats consuming a 2% NaCl diet. Results indicate that bilateral PVN inhibition
      with the GABA-A receptor agonist muscimol (100 pmol/50 nL) caused significantly
      greater reductions of renal and splanchnic sympathetic nerve activity (SNA) and
      mean arterial pressure in hypertensive than in normotensive rats (P<0.01). Thus,
      ongoing PVN neuronal activity seems required for support of hypertension. Next,
      the role of the prototypical cytokine tumor necrosis factor-alpha was
      investigated. Whereas PVN injection of tumor necrosis factor-alpha (0.3 pmol/50
      nL) acutely increased lumbar and splanchnic SNA and mean arterial pressure,
      interfering with endogenous tumor necrosis factor-alpha by injection of
      etanercept (10 MUg/50 nL) was without effect in hypertensive and normotensive
      rats. Next, we determined that although microglial activation in PVN was
      increased in hypertensive rats, bilateral injections of minocycline (0.5 MUg/50
      nL), an inhibitor of microglial activation, failed to reduce lumbar or splanchnic
      SNA or mean arterial pressure in hypertensive or in normotensive rats.
      Collectively, these findings indicate that established Ang II-salt hypertension
      is supported by PVN neuronal activity, but short term maintenance of SNA and
      arterial blood pressure does not depend on ongoing local actions of tumor
      necrosis factor-alpha. 

PMID- 24324039
TI  - "Radical" link between chronic obstructive pulmonary disease and cardiovascular
      disease?

PMID- 24324040
TI  - Aging enhances autonomic support of blood pressure in women.
AB  - The autonomic nervous system plays a central role in both acute and chronic blood
      pressure regulation in humans. The activity of the sympathetic branch of the
      autonomic nervous system is positively associated with peripheral resistance, an
      important determinant of mean arterial pressure in men. In contrast, there is no
      association between sympathetic nerve activity and peripheral resistance in women
      before menopause, yet a positive association after menopause. We hypothesized
      that autonomic support of blood pressure is higher after menopause in women. We
      examined the effect of ganglionic blockade on arterial blood pressure and how
      this relates to baseline muscle sympathetic nerve activity in 12 young (25+/-1
      years) and 12 older postmenopausal (61+/-2 years) women. The women were studied
      before and during autonomic blockade using trimethaphan camsylate. At baseline,
      muscle sympathetic nerve activity burst frequency and burst incidence were higher
      in the older women (33+/-3 versus 15+/-1 bursts/min; 57+/-5 versus 25+/-2
      bursts/100 heartbeats, respectively; P<0.05). Muscle sympathetic nerve activity
      bursts were abolished by trimethaphan within minutes. Older women had a greater
      decrease in mean arterial pressure (-29+/-2 versus -9+/-2 mm Hg; P<0.01) and
      total peripheral resistance (-10+/-1 versus -5+/-1 mm Hg/L per minute; P<0.01)
      during trimethaphan. Baseline muscle sympathetic nerve activity was associated
      with the decrease in mean arterial pressure during trimethaphan (r=-0.74;
      P<0.05). In summary, our results suggest that autonomic support of blood pressure
      is greater in older women compared with young women and that elevated sympathetic
      nerve activity in older women contributes importantly to the increased incidence
      of hypertension after menopause. 

PMID- 24324041
TI  - Validation of uromodulin as a candidate gene for human essential hypertension.
AB  - A recent genome-wide association study identified a locus on chromosome 16 in the
      promoter region of the uromodulin (UMOD) gene that is associated with
      hypertension. Here, we examined the hypertension signal with functional studies
      in Umod knockout (KO) mice. Systolic blood pressure was significantly lower in KO
      versus wild-type (WT) mice under basal conditions (KO: 116.6+/-0.3 mm Hg versus
      WT: 136.2+/-0.4 mm Hg; P<0.0001). Administration of 2% NaCl did not alter
      systolic blood pressure in KO mice, whereas it increased in WT mice by ~33%,
      P<0.001. The average 24-hour urinary sodium excretion in the KO was greater than
      that of WT mice (P<0.001). Chronic renal function curves demonstrate a leftward
      shift in KO mice, suggesting that the relationship between UMOD and blood
      pressure is affected by sodium. Creatinine clearance was increased during salt
      loading with 2% NaCl in the KO mice, leading to augmented filtered Na(+)
      excretion and further Na(+) loss. The difference in sodium uptake that exists
      between WT and KO strains was explored at the molecular level. Urinary tumor
      necrosis factor-alpha levels were significantly higher in KO mice compared with
      WT mice (P<0.0001). Stimulation of primary thick ascending limb of the loop of
      Henle cells with exogenous tumor necrosis factor-alpha caused a reduction in
      NKCC2A expression (P<0.001) with a concurrent rise in the levels of UMOD mRNA
      (P<0.001). Collectively, we demonstrate that UMOD regulates sodium uptake in the
      thick ascending limb of the loop of Henle by modulating the effect of tumor
      necrosis factor-alpha on NKCC2A expression, making UMOD an important determinant
      of blood pressure control. 

PMID- 24324042
TI  - Treatment of hypertension in the oldest old: a critical role for frailty?

PMID- 24324043
TI  - Excess LIGHT contributes to placental impairment, increased secretion of
      vasoactive factors, hypertension, and proteinuria in preeclampsia.
AB  - Preeclampsia, a prevalent hypertensive disorder of pregnancy, is believed to be
      secondary to uteroplacental ischemia. Accumulating evidence indicates that
      hypoxia-independent mediators, including inflammatory cytokines and growth
      factors, are associated with preeclampsia, but it is unclear whether these
      signals directly contribute to placental damage and disease development in vivo.
      We report that LIGHT, a novel tumor necrosis factor superfamily member, is
      significantly elevated in the circulation and placentas of preeclamptic women
      compared with normotensive pregnant women. Injection of LIGHT into pregnant mice
      induced placental apoptosis, small fetuses, and key features of preeclampsia,
      hypertension and proteinuria. Mechanistically, using neutralizing antibodies
      specific for LIGHT receptors, we found that LIGHT receptors herpes virus entry
      mediator and lymphotoxin beta receptor are required for LIGHT-induced placental
      impairment, small fetuses, and preeclampsia features in pregnant mice.
      Accordingly, we further revealed that LIGHT functions through these 2 receptors
      to induce secretion of soluble fms-like tyrosine kinase-1 and endothelin-1, 2
      well-accepted pathogenic factors in preeclampsia, and thereby plays an important
      role in hypertension and proteinuria in pregnant mice. Lastly, we extended our
      animal findings to human studies and demonstrated that activation of LIGHT
      receptors resulted in increased apoptosis and elevation of soluble fms-like
      tyrosine kinase-1 secretion in human placental villous explants. Overall, our
      human and mouse studies show that LIGHT signaling is a previously unrecognized
      pathway responsible for placental apoptosis, elevated secretion of vasoactive
      factors, and subsequent maternal features of preeclampsia, and reveal new
      therapeutic opportunities for the management of the disease. 

PMID- 24324044
TI  - Cervical ganglion block attenuates the progression of pulmonary hypertension via
      nitric oxide and arginase pathways.
AB  - It has been recognized that the sympathetic nervous system is activated in
      pulmonary arterial hypertension (PAH), and abnormal sympathetic hyperactivity
      leads to worsening of PAH via endothelial dysfunction. The purpose of this study
      was to examine whether sympathetic ganglion block (SGB) can treat PAH by
      increasing the availability of nitric oxide (NO). PAH was induced in rats by 50
      mg/kg of subcutaneous monocrotaline. After 2 weeks, daily injections of
      ropivacaine into the left superior cervical ganglion were repeated for 14 days
      (monocrotaline-SGB group). Monocrotaline group received sham SGB with saline,
      whereas control group received saline instead of monocrotaline. PAH was evident
      in monocrotaline group, with right ventricular systolic pressures (47+/-4 mm Hg)
      that were higher than those of controls (17+/-2 mm Hg), whereas SGB significantly
      attenuated monocrotaline-induced PAH (35+/-4 mm Hg). The right/left ventricular
      mass ratios exhibited similar changes to those seen with right ventricular
      pressures. Heart rate variability showed significantly higher sympathetic
      activity in the monocrotaline group. Microscopy revealed a higher proportion of
      muscular arteries with thicker medial walls in the monocrotaline group, which was
      attenuated by SGB. Monocrotaline induced arginase hyperactivity, which was in
      turn decreased by SGB-induced endothelial NO synthase activation. SGB restored
      monocrotaline-induced hypoactivity of superoxide dismutase. In conclusion, SGB
      could suppress PAH and the remodeling of pulmonary arteries via inactivation of
      arginase and reciprocal elevation of NO bioavailability, thus attenuating
      disproportionate hyperactivation of the sympathetic nervous system. 

PMID- 24324046
TI  - The value of N-terminal pro-B-type natriuretic peptide in determining
      antihypertensive benefit: observations from the Anglo-Scandinavian Cardiac
      Outcomes Trial (ASCOT).
AB  - We investigated 3 hypotheses: (1) N-terminal pro-B-type natriuretic peptide (NT
      proBNP) predicts cardiovascular disease events in patients with hypertension, (2)
      NT-proBNP is associated with blood pressure variability, and (3) NT-proBNP
      predicts benefit from antihypertensive regimens. The Anglo-Scandinavian Cardiac
      Outcomes Trial (ASCOT) randomized a subset of 6549 patients at risk with no
      history of coronary heart disease to either atenolol-based or amlodipine-based
      blood pressure-lowering treatment. During 5.5 years of follow-up, 485
      cardiovascular disease cases accrued and were matched with 1367 controls.
      Baseline and 6-month in-trial NT-proBNP were measured. The results show that NT
      proBNP improves cardiovascular disease risk prediction beyond established
      predictors, continuous net reclassification improvement of 22.3% (P<0.0001).
      Furthermore, a 1-mm Hg increase in the SD of systolic blood pressure was
      associated with 2% higher baseline NT-proBNP in a multivariable regression
      analysis (P<0.0001). However, NT-proBNP predicted cardiovascular disease risk
      independently of blood pressure variation (odds ratio per SD increase in log NT
      proBNP 1.24; 95% confidence interval, 1.06-1.45; P=0.007). Atenolol-based
      treatment led to a 69.6% increase in NT-proBNP at 6 months (P<0.0001). In
      contrast, amlodipine-based treatment reduced NT-proBNP by 36.5% (P<0.0001).
      Amlodipine recipients who achieved a 6-month NT-proBNP below the median (61
      pg/mL) were at lower risk of cardiovascular disease when compared with those who
      did not (odds ratio, 0.58; 95% confidence interval, 0.37-0.91) after adjustment
      for confounders inclusive of baseline NT-proBNP and achieved blood pressure. If
      confirmed, these novel results suggest that NT-proBNP, as well as aiding
      cardiovascular disease risk assessment, may also help assess the efficacy of
      specific antihypertensive regimens. Further relevant studies seem warranted. 

PMID- 24324045
TI  - Vascular dysfunction and chronic obstructive pulmonary disease: the role of redox
      balance.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary
      function, inflammation, free radical production, vascular dysfunction, and
      subsequently a greater incidence of cardiovascular disease. By administering an
      acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30),
      we sought to determine the role of redox balance in the vascular dysfunction of
      these patients. Using a double-blind, randomized, placebo-controlled, crossover
      design, patients with COPD and controls were ingested placebo or the antioxidant
      cocktail (vitamin C, vitamin E, alpha-lipoic acid) after which brachial artery
      flow-mediated dilation and carotid-radial pulse wave velocity were assessed using
      ultrasound Doppler. The patients exhibited lower baseline antioxidant levels
      (vitamin C and superoxide dismutase activity) and higher levels of oxidative
      stress (thiobarbituic acid reactive species) in comparison with controls. The
      patients also displayed lower basal flow-mediated dilation (P<0.05), which was
      significantly improved with antioxidant cocktail (3.1+/-0.5 versus 4.7+/-0.6%;
      P<0.05; placebo versus antioxidant cocktail), but not controls (6.7+/-0.6 versus
      6.9+/-0.7%; P>0.05; placebo versus antioxidant cocktail). The antioxidant
      cocktail also improved pulse wave velocity in patients with COPD (14+/-1 versus
      11+/-1 m.s(-1); P<0.05; placebo versus antioxidant cocktail) while not affecting
      controls (11+/-2 versus 10+/-1 m.s(-1); P>0.05; placebo versus antioxidant).
      Patients with COPD exhibit vascular dysfunction, likely mediated by an altered
      redox balance, which can be acutely mitigated by an oral antioxidant. Therefore,
      free radically mediated vascular dysfunction may be an important mechanism
      contributing to this population's greater risk and incidence of cardiovascular
      disease. 

PMID- 24324047
TI  - Targeting the sympathetic nervous system: critical issues in patient selection,
      efficacy, and safety of renal denervation.

PMID- 24324049
TI  - Evidence-based triple antihypertensive therapy yields lower mortality in older
      patients with diabetes mellitus.

PMID- 24324048
TI  - Effects of combination of perindopril, indapamide, and calcium channel blockers
      in patients with type 2 diabetes mellitus: results from the Action In Diabetes
      and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE)
      trial.
AB  - The objective of the present analysis was to determine the effects of a fixed
      combination of perindopril and indapamide in combination with calcium channel
      blockers (CCBs) in patients with type 2 diabetes mellitus. The Action in Diabetes
      and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE)
      trial was a factorial randomized controlled trial. A total of 11 140 patients
      with type 2 diabetes mellitus were randomly assigned to fixed combination of
      perindopril-indapamide (4/1.25 mg) or placebo. Effects of randomized treatment on
      mortality and major cardiovascular outcomes were examined in subgroups defined by
      baseline use of CCBs. Patients on CCB at baseline (n=3427) constituted a higher
      risk group compared with those not on CCB (n=7713), with more extensive use of
      antihypertensive and other protective therapies. Active treatment reduced the
      relative risk of death by 28% (95% confidence interval, 10%-43%) among patients
      with CCB at baseline compared with 5% (-12% to 20%) among those without CCB (P
      homogeneity=0.02) and 14% (2%-25%) for the whole population. Similarly, the
      relative risk reduction for major cardiovascular events was 12% (-8% to 28%)
      versus 6% (-10% to 19%) for those with and without CCB at baseline although the
      difference was not statistically significant (P homogeneity=0.38). There was no
      detectable increase in adverse effects in those receiving CCB. The combination of
      perindopril and indapamide with CCBs seems to provide further protection against
      mortality in patients with type 2 diabetes mellitus. 

PMID- 24324050
TI  - Outcome-driven thresholds for ambulatory pulse pressure in 9938 participants
      recruited from 11 populations.
AB  - Evidence-based thresholds for risk stratification based on pulse pressure (PP)
      are currently unavailable. To derive outcome-driven thresholds for the 24-hour
      ambulatory PP, we analyzed 9938 participants randomly recruited from 11
      populations (47.3% women). After age stratification (<60 versus >=60 years) and
      using average risk as reference, we computed multivariable-adjusted hazard ratios
      (HRs) to assess risk by tenths of the PP distribution or risk associated with
      stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial
      pressure. Among 6028 younger participants (68 853 person-years), the risk of
      cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events
      increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing
      PP levels, the lower boundary of the 95% confidence interval of the successive
      thresholds did not cross unity. Among 3910 older participants (39 923 person
      years), risk increased (P<=0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs
      were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and
      1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower
      boundary of the 95% confidence interval of the HRs associated with stepwise
      increasing PP levels crossed unity at 64 mm Hg. While accounting for all
      covariables, the top tenth of PP contributed less than 0.3% (generalized R(2)
      statistic) to the overall risk among the elderly. Thus, in randomly recruited
      people, ambulatory PP does not add to risk stratification below age 60; in the
      elderly, PP is a weak risk factor with levels below 64 mm Hg probably being
      innocuous.

PMID- 24324051
TI  - Association of phagocytic NADPH oxidase activity with hypertensive heart disease:
      a role for cardiotrophin-1?
AB  - Left ventricular hypertrophy (LVH) is an independent marker of mortality in
      hypertension. Although the mechanisms contributing to LVH are complex,
      inflammation and oxidative stress may favor its development. We analyzed the
      association of the phagocytic NADPH oxidase-mediated superoxide anion release and
      LVH in patients with essential hypertension and the role of cardiotrophin-1 (CT
      1) and interleukin-6 (IL-6), cytokines implicated in cardiac growth. Blood
      pressure, echocardiography data, and serum CT-1 and IL-6 levels were obtained in
      140 subjects: 18 normotensives without LVH, 42 hypertensives without LVH, and 80
      hypertensives with LVH. The NADPH oxidase-dependent superoxide production was
      assessed by chemiluminescence in peripheral blood mononuclear cells. Peripheral
      blood mononuclear cells were stimulated with CT-1 in vitro. Superoxide anion
      production by peripheral blood mononuclear cells associated with LVH and
      correlated with the left ventricular mass index. Serum CT-1 and IL-6 levels,
      which associated with the left ventricular mass index, correlated with superoxide
      production. Serum CT-1 and IL-6 levels were correlated. CT-1 stimulated NADPH
      oxidase superoxide production in peripheral blood mononuclear cells, which
      resulted in an increased release of IL-6. Our results show that superoxide anion
      production by the phagocytic NADPH oxidase associates with hypertensive heart
      disease, being significantly enhanced in hypertensive patients with LVH. This may
      be attributable to the activation of the NADPH oxidase by CT-1 and the subsequent
      release of IL-6. The phagocytic NADPH oxidase may be a therapeutic target in
      hypertensive heart disease. 

PMID- 24324052
TI  - Refractory hypertension: an important clinical phenotype.

PMID- 24324053
TI  - Detection of micrometastases of squamous cell carcinoma tumor cells in muscle
      tissue.
AB  - The aim of this study was to evaluate microarray technology in the detection of
      micrometastases of head and neck squamous cell carcinoma (HNSCC) in muscle
      tissue. Three hundred SCCVII tumor cells were injected intramuscularly into the
      right flank of ten C3H/Km mice. One week later, the animals were euthanized and
      the muscle tissue was taken out. Histology (H&E staining), microarray and reverse
      transcriptase polymerase chain reaction analysis (RT-PCR) of the tissue was
      performed. Histology showed a few tumor cells between the muscle fibers.
      Microarray technology showed the different gene expression pattern of the muscle
      tissue with micrometastases in comparison to normal muscle tissue. Only genes
      with a fold change difference of 10 or greater were considered. Gene expression
      analysis revealed changes in the expression levels of 91 genes of micrometastases
      in muscle tissue. RT-PCR confirmed gene up-regulation. Significant differences in
      gene expression between micrometastases in muscle tissue and pure muscle tissue
      were found. The genes found to be up-regulated could be used to detect
      micrometastases in muscle tissue. 

PMID- 24324054
TI  - Genomic aberrations associated with erlotinib resistance in non-small cell lung
      cancer cells.
AB  - BACKGROUND/AIM: Mechanisms of resistance to epidermal growth factor receptor
      (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC)
      are not fully-understood. In this study we aimed to elucidate remaining unknown
      mechanisms using erlotinib-resistant NSCLC cells. MATERIALS AND METHODS: We
      performed array comparative genomic hybridization (aCGH) to identify genomic
      aberrations associated with EGFR-TKI resistance in erlotinib-resistant PC-9ER
      cells. Real-time polymerase chain reaction (PCR) and immunoblot analyses were
      performed to confirm the results of aCGH. RESULTS: Among the five regions with
      copy number gain detected in PC-9ER cells, we focused on 22q11.2-q12.1 including
      v-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL), the overexpression
      of which seemed to be associated with EGFR-TKI resistance. Blockade of downstream
      phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog
      (AKT) signaling using NVP-BEZ235 suppressed the proliferation of PC-9ER cells,
      implying the involvement of acquired CRKL amplification in EGFR-TKI resistance.
      CONCLUSION: Acquired CRKL amplification was identified as contributing to EGFR
      TKI resistance; this cell line model can be utilized to study this resistance
      mechanism.

PMID- 24324055
TI  - Expression of cyclin d1 and its association with disease characteristics in
      bladder cancer.
AB  - AIM: Invasive urothelial carcinoma of the bladder (UCB) is characterized by
      alterations in cell-cycle regulatory pathways. Defects in the expression of
      cyclin D1, a key cell-cycle regulator, have been implicated in progression of
      various types of cancer. In the present study, we investigated whether cyclin D1
      expression is associated with clinicopathological parameters and whether it has
      any potential prognostic value in determining risk of UCB recurrence. PATIENTS
      AND METHODS: Tissue microarrays containing bladder cancer specimens (n=212) and
      adjacent normal bladder tissues (n=131) were immunostained using an antibody
      against cyclin D1. The association between cyclin D1 and clinicopathological
      parameters including stage, lymph node metastasis, and disease-free survival,
      were evaluated. Cyclin D1 mRNA expression data from human normal bladder (n=14)
      and cancer specimens (n=28) were extracted from the public Oncomine database.
      RESULTS: Cyclin D1 mRNA and protein expression were significantly higher in UCB
      compared to adjacent non-malignant bladder tissue (for mRNA p=0.003, for protein
      p=0.001). Cyclin D1 protein expression was significantly higher in non-invasive
      tumors than in muscle-invasive UCB (p=0.016). Among patients with muscle-invasive
      UCB, increased cyclin D1 expression in tumor cells significantly correlated with
      lymph node metastasis (p<0.001), and there was a trend of cyclin D1 together with
      lymph node positivity to be associated with disease recurrence (p=0.678). Loss of
      nuclear cyclin D1 expression in tumor cells was likewise significantly associated
      with the presence of lymph node metastasis (p<0.001). CONCLUSION: Altered
      expression of cyclin D1 is associated with lymph node metastasis and risk of UCB
      recurrence. Cyclin D1 expression may therefore have clinical value as a
      prognostic marker and potential therapeutic target.

PMID- 24324056
TI  - Reliable housekeeping gene combination for quantitative PCR of lymph nodes in
      patients with prostate cancer.
AB  - BACKGROUND: To reliably compare the results of gene expression studies, the
      expression of the target gene should be normalized to the expression of a
      reference gene. For lymph node metastases of prostate cancer, no data on
      polymerase chain reaction (PCR) normalization have yet been reported. We aimed to
      determine the most reliable reference gene combination for this purpose in
      patients with prostate cancer. MATERIALS AND METHODS: Ten histologically-
      positive and ten negative lymph nodes of patients with prostate cancer were
      analyzed respectively. Expression of six candidate reference genes was
      comparatively assessed with quantitative Real-time PCR. The most stably-expressed
      gene combination was determined with geNorm software version 3.4. RESULTS:
      Hypoxanthine phosphoribosyltransferase-1 (HPRT1) and TATA box binding protein
      (TPB) were found to be the most stably expressed genes, with their combination
      having an expression stability value of M=0.17. CONCLUSION: Gene combination
      HPRT1 and TPB has the potential to be utilized for normalization in gene
      profiling assessment of metastatic and non-metastatic pelvic lymph node tissue
      from patients with prostate cancer.

PMID- 24324057
TI  - DNA hypermethylation as a predictor of PSA recurrence in patients with low- and
      intermediate-grade prostate cancer.
AB  - BACKGROUND: DNA CpG island hypermethylation causes gene silencing and is a common
      event in prostate carcinogenesis and progression. We investigated its role as a
      possible prognostic marker in patients with PCA Gleason score <=7. PATIENTS AND
      METHODS: We used a quantitative, methylation-specific PCR to analyze methylation
      patterns at five gene loci (APC, GSTP1, PTGS2, RARbeta and TIG1) in 84 prostate
      cancer (PCA) tissues (Gleason Score <=7). Methylation was correlated with
      established clinico-pathological parameters (preoperative PSA, pathological
      Gleason score, extraprostatic extension, seminal vesicle penetration, lymph node
      involvement, surgical margins and age) and PSA recurrence. RESULTS: DNA
      hypermethylation was frequently detected at APC (95.2%), GSTP1 (84.5%), PTGS2
      (100%), RAR-beta (81.0%) and TIG1 (95.2%). DNA hypermethylation was correlated
      with Gleason Score (p=0.027; PTGS2) and lymph node involvement (p=0.024;
      RARbeta). High methylation levels at RARbeta (p=0.023) was a significant
      predictor of PSA recurrence following radical prostatectomy. CONCLUSION: The
      analysis of DNA hypermethylation provides prognostic information in prognosis of
      low- and intermediate-grade PCA.

PMID- 24324058
TI  - In vitro analysis of the relationships between metallothionein expression and
      cisplatin sensitivity of non-small cellular lung cancer cells.
AB  - BACKGROUND: Cisplatin-based therapy is a pivotal type of chemotherapy for non
      small cell lung cancer (NSCLC) and chemoresistance to cisplatin represents one of
      the most significant barriers to improving long-term clinical outcomes. MATERIALS
      AND METHODS: The present study aimed at examining metallothionein (MT) expression
      in six NSCLC cell lines as well as examining effects of exposure to cisplatin on
      MT expression in the most cisplatin-resistant (97/97) and the cisplatin-sensitive
      (DV90) cell lines. RESULTS: The most cisplatin-resistant NSCLC cell line [97/97;
      (IC50)=4.659 MUM] exposed to the highest concentration of cisplatin (10 MUM)
      exhibited decreased nuclear MT expression (MTn=6) compared to cells cultured in
      medium with a lower concentration of cisplatin (0, 1 and 5 MUM) (MTn=12). A
      higher cytoplasmic metallothionein expression (MTc=6) was found in the 97/97 cell
      line exposed to the highest concentration of cisplatin (10 MUM), compared to
      cells cultured in the medium with lower concentrations of cisplatin (0, 1 and 5
      MUM) (MTc=3). The most cisplatin-sensitive NSCLC cell line (DV90; IC50=0.184 MUM)
      was characterized by a significant decrease of both nuclear and cytoplasmic MT
      expression with increasing cisplatin concentrations (5 vs. 10 MUM). CONCLUSION:
      Nuclear and cytoplasmic expression of MT has no significant impact on the
      development of cisplatichemoresistance in NSCLC cell lines. The present study
      suggests that cisplatin resistance in NSCLC is metallothionein-independent.

PMID- 24324060
TI  - Activation of DNA damage response by antitumor therapy counteracts the activity
      of vinca alkaloids.
AB  - BACKGROUND/AIM: Anthracyclines have been proven able to reduce the activity of
      vinca alkaloids by induction of cell-cycle arrest. The present study aims at
      identifying the critical initiation steps of signal transduction which transduce
      the inhibitory effects on the cytotoxicity of vinca alkaloids. MATERIALS AND
      METHODS: Several new cytostatic drug classes were evaluated together with
      vincristine in tumor cell lines and patients' tumor cells. RNA interference was
      used for molecular analyses. RESULTS: Inhibition of vincristine was observed by
      all cytostatic drugs, which induced cell-cycle arrest. Knockdown of proteins of
      the DNA damage response ascribed the inhibitory effect to a common pathway
      involving Chk-1, p53 and p21. Upstream of Chk-1 signal transduction depended on
      both ATM and ATR for all drugs except methotrexate. CONCLUSION: We have
      identified critical signaling steps of the DNA damage response system activated
      by cytostatic drugs, which reduce the anti-tumor activity of vinca alkaloids. The
      obtained results encourage the development of novel therapeutic strategies to
      prevent pathway interactions based on the molecular understanding of drug action
      and drug-drug interactions.

PMID- 24324059
TI  - Soluble epoxide hydrolase deficiency inhibits dextran sulfate sodium-induced
      colitis and carcinogenesis in mice.
AB  - Soluble epoxide hydrolase (sEH) hydrolyses/inactivates anti-inflammatory
      epoxyeicosatrienoic acids (EETs) to their corresponding diols, and targeting sEH
      leads to strong anti-inflammatory effects. In the present study, using a tissue
      microarray and immunohistochemical approach, a significant increase of sEH
      expression was identified in ulcerative colitis (UC)-associated dysplasia and
      adenocarcinoma. The effects of deficiency in the sEH gene were determined on
      dextran sulfate sodium (DSS) colitis-induced carcinogenesis. The effects of EETs
      on lipopolysaccharide (LPS)-activated macrophages were analyzed in vitro. With
      extensive histopathological and immunohistochemical analyses, compared to wild
      type mice, sEH(-/-) mice exhibited a significant decrease in tumor incidence
      (13/20 vs. 6/19, p<0.05) and a markedly reduced average tumor size (59.62+/-20.91
      mm(3) vs. 22.42+/-11.22 mm(3)), and a significant number of pre-cancerous
      dysplasia (3+/-1.18 vs. 2+/-0.83, p<0.01). The inflammatory activity, as measured
      by the extent/proportion of erosion/ulceration/dense lymphoplasmacytosis (called
      active colitis index) in the colon, was significantly lower in sEH(-/-) mice
      (44.7%+/-24.9% vs. 20.2%+/-16.2%, p<0.01). The quantitative polymerase chain
      reaction (qPCR) assays demonstrated significantly low levels of
      cytokines/chemokines including monocyte chemoattractant protein (MCP-1),
      inducible nitric oxide synthase (iNOS), vasopressin-activated calcium-mobilizing
      (VCAM-1), interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha). In vitro, LPS-activated macrophages treated with 14,15-EET showed a
      significant reduction of LPS-triggered IL-1beta and TNF-alpha expression.
      Eicosanoic acid metabolic profiling revealed a significant increase of the ratios
      of EETs/ dihydroeicosatrienoic acids (DHETs) and epoxyoctadecennoic
      acid/dihydroxyoctadecenoic acid (EpOMEs/DiHOMEs). These results indicate that sEH
      plays an important role in the development of colitis and in inducing
      carcinogenesis. 

PMID- 24324061
TI  - Expression of mRNAs of Urocortin in the STKM-1 gastric cancer cell line.
AB  - BACKGROUND: Urocortin is analogous to corticotrophin-releasing factors (CRFs) and
      a member of the CRF family. We previously demonstrated that urocortin mRNAs were
      expressed in both human and rat glioma cell lines, and that some of these lines
      transcribed the receptors. We hypothesize that urocortin might also be expressed
      in a gastric cancer cell line. The aim of the present study was to clarify the
      expression of mRNAs of urocortin1 (UCN1), -2 and -3 and of CRF and CRF receptors
      1 and 2 in a gastric cancer cell line. MATERIALS AND METHODS: STKM-1 a poorly
      differentiated adenocarcinoma cell line was used. Transcripts in the cells were
      analyzed using cDNA. The fluctuation of mRNA with cellular stress, such as the
      one caused by a chemotherapeutic agent, serum supplementation and forskolin was
      examined. RESULTS: Transcripts of UCN1, -2 and CRFR2 were expressed. No changes
      in transcription of UCN1 and UCN2 were observed with cellular stress. However,
      expression of CRFR2 mRNA transcripts significantly increased after an initial 24
      h exposure to forskolin. CONCLUSION: Expression of the mRNAs of UCN1, 2 and CRFR2
      was confirmed in the human gastric cancer cell line, STKM-1. Although the
      quantity of CRFR2 transcripts varied with forskolin, the overall transcription
      pattern was not influenced by cellular stimuli.

PMID- 24324062
TI  - Zoledronic acid as an antimetastatic agent for different human tumor cell lines.
AB  - BACKGROUND: Zoledronic acid effectively reduces skeletal events in patients with
      metastatic disease. The results of pre-clinical and emerging clinical data
      suggest an additional activity of zoledronic acid as an antitumor agent,
      interfering with the growth and dissemination of malignant cells. However, the
      mechanisms by which zoledronic acid impairs tumor progression are practically
      unknown. In the present study, we aimed to investigate the impact of zoledronic
      acid on invasion and colony formation ability of different human tumour cell
      lines. MATERIALS AND METHODS: Human ovarian (SKOV3), colonic (HCT116),
      endometrial (HEC1A and Ishikawa) and breast cancer (MCF-7, MDA-MB-231, HCC1937,
      SKBR3 and T47D) cell lines were treated with different concentrations (10-100
      MUM) of zoledronic acid and analyzed using 3D assays to test their invasiveness
      and their ability to grow anchorage-independently, both hallmarks of aggressive
      tumor cell behavior. RESULTS: The most intense effect of the drug on tumor
      invasion was observed on MDA-MB-231 cells, but at high concentrations HEC1A,
      SKOV3 and SKBR3 cells also exhibited reduced invasion capacity. We also found a
      significant reduction of colony formation under zoledronic acid treatment in MCF
      7, T47-D, HCT116, Ishikawa, HEC1A and SKOV3 cells. CONCLUSION: Zoledronic acid
      presents an interesting potential for use as anti-metastatic agent for different
      solid tumor types, affecting relevant steps of tumor dissemination.

PMID- 24324063
TI  - Silicate fiber-based 3D cell culture system for anticancer drug screening.
AB  - BACKGROUND: Three-dimensional (3D) in vitro cultures can recapitulate the
      physiological in vivo microenvironment. 3D Modeling techniques have been
      investigated and applied in anticancer drug screening. MATERIALS AND METHODS: A
      silicate fiber scaffold was used for 3D cell cultures, and used to model the
      efficacy of anticancer drugs, such as mytomicin C and doxorubicin. RESULTS: A
      unique 3D structure was observed in 13 human tumor cell lines on scaffold, and
      these cells exhibited higher drug resistance than cells in two-dimensional (2D)
      cultures. Furthermore, the production of lactate and expression of the nuclear
      factor-kappa B (NF-kappaB)-regulated genes B cell lymphoma-2 (BCL2),
      cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) were
      higher in 3D cultures than in 2D cultures. CONCLUSION: These findings suggest
      that a 3D model using a silicate fiber scaffold can mimic features of cancer, and
      is also a suitable model for the evaluation of anticancer drugs in vitro.

PMID- 24324064
TI  - Prokineticin 1 expression in gastrointestinal tumors.
AB  - AIM: We studied prokineticin 1 (PROK1) expression in human gastrointestinal
      carcinomas by immunohistochemistry. MATERIALS AND METHODS: PROK1 expression was
      examined in human gastrointestinal cancer cell lines and primary gastrointestinal
      lesions. In addition the relationship between the number of blood vessels and
      PROK1 expression in these primary lesions was examined. RESULTS: PROK1 expression
      was observed in gastrointestinal cancer cell lines. PROK1 expression was not
      observed in healthy gastrointestinal mucosa, but was observed in the primary
      lesions in 23 out of 98 (31.6%) patients with colorectal cancer, 19 out of 55
      (34.5%) patients with gastric cancer, and 5 of 10 (50%) patients with cancer of
      the small intestine. PROK1 expression was observed in many patients with advanced
      gastrointestinal cancer. The number of blood vessels in PROK1-positive primary
      gastrointestinal lesions was higher than that in PROK1-negative primary lesions.
      CONCLUSION: PROK1 expression might be related to the extent of malignancy in
      gastrointestinal cancer.

PMID- 24324065
TI  - Regulations of ABCB1 and ABCG2 expression through MAPK pathways in acute
      lymphoblastic leukemia cell lines.
AB  - BACKGROUND: One of the major causes of failure in chemotherapy for patients with
      acute lymphoblastic leukemia (ALL) is the acquisition of multidrug resistance
      (MDR). Predominant mechanisms for MDR acquisition include the overexpression of
      efflux pumps. In the present study, the regulation of the expression of two genes
      that encode efflux pumps, ATP-binding cassette, sub-family B, member 1 (ABCB1)
      and ABCG2, through mitogen-activated protein kinase (MAPK) pathways was examined.
      MATERIALS AND METHODS: ABCB1 and ABCG2 mRNAs were quantified in a T-ALL cell
      line, CCRF-HSB-2 and a B-ALL cell line, YAMN90 using real-time RT-PCR. Changes in
      the mRNA amounts of these genes were examined after activation or inhibition of
      MAPK/extracellular signal-regulated kinase (ERK) pathway and c-Jun NH2-terminal
      kinase (JNK) pathway. RESULTS: Activation of MAPK/ERK pathway up-regulated ABCB1
      expression but down-regulated ABCG2 expression. Activation of JNK pathway up
      regulated ABCG2 gene expression. CONCLUSION: The expressions of ABCB1 and ABCG2
      genes were regulated through MAPK/ERK and JNK pathways in the human ALL cell
      lines.

PMID- 24324066
TI  - Green tea polyphenol epigallocatechin 3-gallate, contributes to the degradation
      of DNMT3A and HDAC3 in HCT 116 human colon cancer cells.
AB  - BACKGROUND: Colon cancer is still the second leading cause of cancer deaths in
      the United States. Epigenetic gene silencing involving DNA methyltransferases
      (DNMTs) and histone deacetylases (HDACs) plays an important role in the
      progression of colon cancer. MATERIALS AND METHODS: In the present study we found
      that the sensitivity of colon cancer cells to methylation plays a role in its
      response to alternative therapy involving the green tea polyphenol,
      epigallocatechin 3-gallate. HDAC and DNMT protein expression were reduced when
      methylation-sensitive HCT 116 human colon cancer cells was treated with EGCG, but
      was relatively stable in the HT-29 cell line. This decrease in expression may be
      partially explained by our finding that DNMT3A and HDAC3 are degraded in the
      methylation-sensitive colon cancer cells in part by inhibiting their association
      with the E3 ubiquitin ligase, UHRF1. CONCLUSION: These findings provide a
      rationale for the development of a targeted therapy for methylation-sensitive
      colon cancer that can include EGCG in combination with other DNMT and HDAC
      inhibitors.

PMID- 24324067
TI  - Genetically-engineered human neural stem cells with rabbit carboxyl esterase can
      target CNS lymphoma.
AB  - BACKGROUND: Despite advances in its treatment, CNS lymphoma remains a devastating
      disease. Taking advantage of the tumour-tropic properties of neural stem cells
      (NSCs) is a novel therapeutic strategy. To apply this strategy to the treatment
      of CNS lymphoma, we investigated the role of NSCs expressing carboxyl esterase
      (HB1.F3.CE), which activates irinotecan. MATERIALS AND METHODS: In order to find
      in vitro bystander effects of engineered NSCs, we performed cell viability
      assays. In vivo, the HB1.F3.CE cells were injected into the brain of mice with
      orthotopic CNS lymphoma. Mice were then treated with irinotecan by systemic
      administration. RESULTS: The HB1.F3.CE cells significantly inhibited the growth
      of Raji cells with irinotecan treatment. In vivo, the HB1.F3.CE cells migrated
      into the tumour and significantly reduced tumour volume. In addition, survival of
      mice was prolonged by treatment with HB1.F3.CE and irinotecan. CONCLUSION:
      Transplantation of human NSCs encoding CE into brain, combined with irinotecan
      therapy, may be an effective treatment regimen for CNS lymphoma.

PMID- 24324068
TI  - EGFRvIII--a stable target for anti-EGFRvIII therapy.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) gene alterations play
      important roles in pathogenesis of glioblastoma. Antibodies against EGFRvIII have
      been recently developed. Their efficacy depends on numerous factors, including
      the co-existence of EGFRvIII with other genetic alterations, and especially with
      point mutations of EGFR. MATERIALS AND METHODS: We examined 91 patients diagnosed
      with glioblastoma in order to determine the prevalence and mutual relationships
      between EGFR alterations. Real-time polymerase chain reaction (real-time PCR),
      fluorescent in situ hybridization (FISH), and sequencing were used to analyze
      prevalence of the amplification of EGFR gene, polysomy of chromosome 7, EGFRvIII
      mutation, and point mutations in exons 7-8 and 15 of EGFR. RESULTS: We revealed
      that all these alterations can occur independently from each other. Nevertheless,
      the co-existence of EGFRvIII mutation and excessive copies of EGFR gene was
      observed in most cases (10/14). Similarly, the point mutations in exons 7-8 and
      15 co-existed with an excessive number of EGFR copies in nearly all cases.
      CONCLUSION: EGFRvIII is a reliable and stable target for anti-EGFRvIII therapy.

PMID- 24324070
TI  - Lung cancer cell line sensitivity to Zoledronic acid is BAX-dependent.
AB  - BACKGROUND: Zoledronate (Zol), an anti-osteoclastic and anticancer drug, is used
      to control bone metastasis in several cancer types, including non-small cell lung
      cancer (NSCLC). However, the mechanisms behind Zol resistance in NSCLC are
      unclear. MATERIALS AND METHODS: Zol-resistant cell lines were developed by
      repeated treatment of A549 and H1650 NSCLC cell lines with Zol. We measured cell
      proliferation and apoptosis following Zol treatment and also examined the BCL2
      superfamily expression. RNAi was used to confirm the role of key molecules in
      development of resistance. RESULTS: Repeated Zol treatment engendered resistance,
      in which apoptosis induction was attenuated. From the BCL2 superfamily, BAX was
      commonly down-regulated in resistant cells, and silencing of BAX in parental cell
      lines also induced drug resistance. CONCLUSION: Repeated treatment of NSCLC cell
      lines with Zol leads to drug resistance, which is in part due to BAX down
      regulation.

PMID- 24324069
TI  - Dichamanetin inhibits cancer cell growth by affecting ROS-related signaling
      components through mitochondrial-mediated apoptosis.
AB  - BACKGROUND/AIM: Dichamanetin is a C-benzylated flavanone isolated as a major
      secondary metabolite from Piper sarmentosum, a plant used as a spice in Southeast
      Asia. This study aimed to investigate the path through which dichamanetin exerts
      its antiproliferative effect. MATERIALS AND METHODS: The study of several
      signaling cellular components, namely, reactive oxygen species (ROS) levels,
      nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
      transcription factor, mitochondrial membrane potential, DNA binding, poly ADP
      ribose polymerase (PARP1) inhibition and proteasome inhibition was performed
      using an enzyme-linked immunosorbent (ELISA) assay, cell sorting, and western
      blot. RESULTS: Dichamanetin significantly reduced the cell viability of various
      types of human cancer cells (HT-29 colon, DU145 prostate, and MDA-MB-231 breast
      cancer) in a concentration- and time-dependent manner and induced G1 arrest of
      the cell cycle. It was also demonstrated that the selective cytotoxic effect of
      dichamanetin in cancer cells is mediated by the induction of oxidative stress.
      CONCLUSION: Our findings suggest that dichamanetin isolated from an edible herb
      has cancer chemotherapeutic potential.

PMID- 24324071
TI  - Suppression of OCT4B enhances sensitivity of lung adenocarcinoma A549 cells to
      cisplatin via increased apoptosis.
AB  - BACKGROUND: Resistance to chemotherapy in lung adenocarcinoma remains a major
      obstacle. We examined the potential role of Octamer-binding transcription factor
      4B (OCT4B) in enhancing sensitivity of lung adenocarcinoma cells to cisplatin.
      MATERIALS AND METHODS: RNAi interference was used to examine the role of OCT4B in
      cisplatin-treated A549 cells. Cells were transfected with OCT4B siRNA prior to a
      48-h cisplatin treatment. Propidium iodide (PI) and caspase-3 staining were used
      to determine cell viability and apoptosis. Cell-cycle analysis was performed to
      evaluate alterations in phase distribution. RESULTS: OCT4B suppression in cells
      increased the number of non-viable, PI(+), and apoptotic, caspase-3(+) cells in
      the presence and absence of cisplatin treatment. Importantly, cisplatin treatment
      of OCT4B-suppressed cells resulted in a marked transition of cells from G0/G1 to
      G2/M phase. CONCLUSION: Silencing of OCT4B confers sensitivity to cisplatin
      treatment in A549 cells via cell-cycle regulation, increased proliferation and
      enhancement of cisplatin-induced apoptosis. OCT4B clearly protects A549 cells
      from apoptosis.

PMID- 24324072
TI  - Comparison of minichromosome maintenance proteins (MCM-3, MCM-7) and
      metallothioneins (MT-I/II, MT-III) expression in relation to clinicopathological
      data in ovarian cancer.
AB  - BACKGROUND: Despite great progress in the understanding of ovarian cancer
      biology, clinicopathological data (i.e. grade, stage, histological type and
      residual disease after surgery) seem to be the most important prognostic factors.
      MATERIALS AND METHODS: The present study aimed to investigate the relationship
      between expression of minichromosome maintenance proteins (MCM-3, MCM-7),
      metallothioneins (MT-I/II, MT-III), and Ki-67 in 103 ovarian cancer cases, mostly
      of the serous histological type. RESULTS: Statistical analysis revealed strong
      positive correlations in the expression of MCM-3 vs. Ki-67 (r=0.492), MCM-7 vs.
      Ki-67 (r=0.651), and MCM-3 vs. MCM-7 (r=0.515) (all p<0.0001). The Kruskal-Wallis
      test showed an association of increased expression of MCM-3 and Ki-67 with
      increasing grade of histological malignancy (p=0.0011, p=0.029, respectively).
      Regarding clinical progression, cytoplasmic MT-I/II expression was significantly
      higher in more advanced disease stages (III+IV vs. I+II; p=0.0247). CONCLUSION:
      Due to the correlations shown here, the determination of MCM proteins as
      proliferation markers of ovarian cancer, should be strongly considered.

PMID- 24324073
TI  - Small molecule-based chemotherapeutic approach in p16-positive and -negative
      HNSCC in vitro.
AB  - BACKGROUND: Incidence of oropharyngeal head and neck squamous cell carcinoma
      (HNSCC) induced by the human papilloma virus (HPV) is rising. HNSCC is the sixth
      most common neoplasia worldwide. The survival rate remains poor, thus innovative
      therapy approaches are necessary. Everolimus, an inhibitor of the mammalian
      target of rapamycin, as well as the multi-tyrosine kinase inhibitors sorafenib
      (targeting vascular endothelial growth factor receptor, platelet-derived growth
      factor receptor and RAF) and sunitinib (targeting vascular endothelial growth
      factor receptor, platelet-derived growth factor receptor, stem cell factor
      receptor, RET proto-oncogene and colony-stimulating factor), have shown a
      remarkable antitumor effect against various tumor entities, with moderate side
      effects. These drugs are administered orally, which should lead to higher patient
      compliance and less hospitalisation. AIM: This study sought to evaluate the
      expression of PDGFR alpha/beta and hypoxia-inducible factor-1alpha (HIF-1alpha)
      and their alterations induced by everolimus, sorafenib and sunitinib in
      chemonaive HPV-positive and HPV-negative HNSCC. To our knowledge, this is the
      first in vitro study to investigate such cases. MATERIALS AND METHODS: We
      incubated HPV-positive CERV196 and HPV-negative HNSCC 11A and 14C cells for 2 to
      8 days with increasing concentration of drugs. Expression of PDGFR alpha/beta and
      HIF-1alpha was measured by enzyme-linked immunosorbent assay and compared to a
      chemonaive controls. RESULTS: Our study showed that PDGFR alpha/beta and HIF
      1alpha were expressed in all three cell lines. Incubation with everolimus,
      sorafenib or sunitinib led to a decrease in PDGFR alpha/beta and HIF-1alpha
      expression, depending on the HPV status. A statistically significant alteration
      of PDGFR alpha/beta was detected in CERV196 only. Thus, HPV-positive HNSCC
      exhibited a higher sensitivity to the drugs used compared to HPV-negative HNSCC
      11A and 14C tumor cells. A significant reduction of HIF-1alpha was measured for
      HNSCC 11A and 14C only. An escalation of drug concentration had no significant
      effect. CONCLUSION: We showed that these novel agents led to a significant
      reduction of PDGFR and HIF-1alpha, depending on the HPV status. HPV positivity is
      associated with increased chemosensitivity and may be associated with better
      locoregional control and overall patient survival compared to HPV negativity.
      Further studies are necessary to investigate the efficacy and safety of these
      agents in the treatment of HPV-positive and -negative HNSCC in vivo.

PMID- 24324074
TI  - Association of X-ray repair cross-complementing-6 genotypes with childhood
      leukemia.
AB  - BACKGROUND: The Non-homologous end-joining repair gene XRCC6/Ku70 plays an
      important role in the repair of DNA double-strand breaks (DSBs), and has been
      found to be involved in the carcinogenesis of many types of cancers including
      oral, prostate, breast and bladder cancer. However, the contribution of XRCC6 to
      childhood leukemia has yet to be studied. In the present study, we investigated
      the association of XRCC6 genotypes with the risk of childhood leukemia. MATERIALS
      AND METHODS: Two hundred and sixty-six patients with childhood leukemia and an
      equal number of age-matched healthy controls recruited in Central Taiwan, were
      genotyped investigating these polymorphisms' association with childhood leukemia.
      RESULTS: As for XRCC6 promoter T-991C, patients carrying the TC genotype had a
      significantly increased risk of childhood leukemia compared with the TT wild-type
      genotype [odds ratio (OR)=2.30, 95% confidence interval (CI)=1.38-3.84,
      p=0.0047]. Meanwhile, the genotypes of XRCC6 promoter C-57G, A-31G and intron3
      were not statistically associated with childhood leukemia risk. CONCLUSION: Our
      findings suggest that the XRCC6 genotype could serve as a predictor of childhood
      leukemia risk and XRCC6 could serve as a target for personalized medicine and
      therapy.

PMID- 24324075
TI  - Associations of cyclooxygenase 2 polymorphic genotypes with bladder cancer risk
      in Taiwan.
AB  - AIM: Bladder cancer is the sixth most common cancer worldwide and its incidence
      is particularly high in southwestern Taiwan. However, the genetic contribution to
      its etiology is not well-understood. The aim of this study is to evaluate the
      association of cyclooxygenase 2 (Cox-2) polymorphic genotypes with Taiwan bladder
      cancer patients. MATERIALS AND METHODS: Six polymorphic variants of Cox-2 were
      analyzed regarding their association with bladder cancer risk, and three hundred
      and seventy-five patients with bladder cancer and same amount of age- and gender
      matched healthy controls recruited were genotyped by the PCR-RFLP method.
      RESULTS: Among the six polymorphic sites examined, only the Cox-2 promoter G-765C
      (rs20417) genotypes were positively associated with bladder cancer risk
      (p=0.0102). Individuals with the Cox-2 -765GC genotypes were associated with
      higher prostate cancer risk than those with -765GG. CONCLUSION: Our findings
      provide evidence that the C allele of Cox-2 promoter G-765C may be associated
      with the overexpression of COX-2 during bladder cancer development and may be a
      useful marker for the early detection of bladder cancer.

PMID- 24324076
TI  - A novel chemotherapeutic arene ruthenium(II) drug Rawq01 altered the effect of
      microRNA-21 on PTEN/AKT signaling pathway in esophageal cancer cells.
AB  - AIM: Organometallic arene Ru(II) complexes have long been considered as most
      promising substitutes for cisplatinum as an anti-tumor drug, with low toxicity
      towards human normal cells and high selectivity to tumor cells. In this study, we
      synthesized a novel arene Ru(II) drug named Rawq01. We evaluated its activity in
      an in vitro model of esophageal cancer (ESCC) and further explored the cellular
      signaling pathways altered by Rawq01. MATERIALS AND METHODS: 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphe nyltetrazolium bromide (MTT) assay, colony
      forming assay and apoptosis assays were used to evaluate the antitumor activity
      of Rawq01. We treated ESCC cells with Rawq01 alone or combined with microRNA
      21(miR-21) and LY294002 to explore whether Rawq01 altered the effect of miR-21 on
      PTEN/AKT signaling pathway in ESCC cell. RESULTS: ESCC cells were sensitive to
      RAWQ01. We also found that Rawq01 up-regulated the expression of PTEN through mir
      21 inhibition and therefore inhibited the PI3K-AKT pathway. Furthermore, when we
      combined Rawq01 treatment with miR-21 inhibitor or LY294002, the inhibitory
      effect of Rawq01 was significantly enhanced. CONCLUSION: The effect of miR-21 on
      PTEN/AKT signaling pathway is abrogated by the novel arene Ru(II) drug Rawq01.
      Our data may be useful for the future development of a chemosensitizing
      strategies through manipulating microRNA expression for tumor treatment.

PMID- 24324077
TI  - E2F5 as an independent prognostic factor in esophageal squamous cell carcinoma.
AB  - BACKGROUND: E2F Transcription Factor 5 Protein (E2F5) is considered to act
      primarily as a transcriptional repressor in the cell cycle. However, its
      expression and role in esophageal squamous cell carcinoma (ESCC) have not been
      investigated. We examined whether the expression of E2F5 is related to the
      clinicopathological features and prognosis of patients with ESCC. MATERIALS AND
      METHODS: The expression of E2F5 was analyzed by immunohistochemistry in 64
      primary tumor samples obtained from patients with ESCC who had undergone curative
      esophagectomy between 1998 and 2009. According to the expression of E2F5 in tumor
      cells, cases were divided into E2F5-positive (27 cases) and -negative groups (37
      cases). The relationship of various clinicopathological features and prognosis
      with the E2F5 status, were analyzed. RESULTS: In the clinicopathological
      analysis, the proportion of poorly-differentiated tumors was significantly higher
      in the E2F5-positive group than in the E2F5-negative group (p=0.027). The 5-year
      survival rate of the E2F5-positive group was 39.3%, which was significantly
      poorer than that of the E2F5-negative group (83.8%) (p=0.006). In multivariate
      analysis, the expression of E2F5 was one of the most important independent
      prognostic factors after radical esophagectomy. CONCLUSION: The expression of
      E2F5 in ESCC may be correlated with a worse prognosis of patients with ESCC.

PMID- 24324078
TI  - Evaluation of stem cell marker gene expression in canine prostate carcinoma- and
      prostate cyst-derived cell lines.
AB  - BACKGROUND/AIM: In human prostate cancer cells with a stem cell-like character
      (cancer stem cells, CSC) are considered to play a major role in disease
      development, progression and relapse. Aim of the study was to evaluate if similar
      cells are present and active in canine prostate cancer providing a naturally
      occurring mammalian model for the development of therapeutic approaches targeting
      CSC. MATERIALS AND METHODS: Stem cell marker expression of CD133, CD44, C-KIT,
      CD34, ITGA6, OCT4, DDX5 and MELK in canine prostate carcinomas and prostate cyst
      cell lines were screened by Polymerase Chain Reaction (PCR), quantitative
      Polymerase Chain Reaction (qPCR) and partially analysed by flow cytometry.
      RESULTS: Marker analyses by PCR and qPCR, revealed a complex expression pattern
      for the analysed marker genes, providing a characteristic marker pattern for the
      studied cell lines. Thereby CD44, CD133, ITGA6 and DDX5 showed the most prominent
      expression in the analysed cell lines. CONCLUSION: The results revealed a
      characteristic stem cell marker expression in the analysed cell lines, indicating
      the presence of CSC in canine prostate cancer.

PMID- 24324079
TI  - Acquired resistance to chemotherapy in lung cancer cells mediated by prolonged
      nitric oxide exposure.
AB  - BACKGROUND: The effect of extended exposure of cancer cells to nitric oxide (NO),
      an endogenous mediator frequently found increased in tumors, is largely unknown.
      In the present study, the effect of long-term NO exposure on chemotherapeutic
      resistance was investigated in lung cancer cells. MATERIALS AND METHODS: The
      effect of long-term exposure of human lung cancer cells to NO on susceptibility
      to chemotherapeutic agents-induced apoptosis was analyzed by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, co-staining of
      Hoechst 33342 and propidium iodide (PI), and Annexin V detection. The expression
      of survival-related proteins was analyzed by western blot. Gene manipulation was
      used for evaluation of the effect of expression proteins on susceptibility of the
      cells to chemotherapeutic agent-mediated death. RESULTS: Long-term NO exposure
      for 7-14 days rendered the lung cancer cells resistant to cisplatin, doxorubicin,
      and etoposide dose- and time-dependently. The underlying mechanism was found to
      involve the adaptive responses of the cells, by increasing survival due to
      increase in the level of caveolin-1 (CAV1) and anti-apoptotic B-cell lymphoma-2
      (BCL2), and up-regulation of activated protein kinase B (AKT). The gene
      manipulation study revealed that the increase of activated AKT and BCL2 was
      responsible for the resistance to all tested drugs, while the up-regulation of
      CAV1 only attenuated cell death mediated by doxorubicin and etoposide.
      Interestingly, NO-mediated drug resistance was found to be reversible when cells
      were further cultured in the absence of NO for five days. CONCLUSION: These
      findings reveal the novel role of NO in the tumor environment, in attenuating
      chemotherapeutic susceptibility and this could be beneficial in contriving
      strategies to treat the disease.

PMID- 24324080
TI  - Lobarstin enhances chemosensitivity in human glioblastoma T98G cells.
AB  - BACKGROUND/AIM: Lobarstin is a metabolite occurring from the Antarctic lichen
      Stereocaulon alpnum. Human glioblastoma is highly resistant to chemotherapy with
      temozolomide. Lobarstin was examined for its effect on glioblastoma. MATERIALS
      AND METHODS: Temozolomide-resistant T98G cells were subjected to toxicity test
      with temozolomide and/or lobarstin. DNA damage and recovery was assessed by the
      alkaline comet assay and expression of DNA repair genes was examined by RT-PCR
      and western blot analysis. RESULTS: Lobarstin alone at 40 MUM was toxic against
      T98G, but had no effect in primary human fibroblasts. Co-treatment of lobarstin
      with temozolomide yielded enhanced toxicity. Temozolomide-alone or with lobarstin
      co-treatment gave similar extent of DNA damage. However, the recovery was reduced
      in co-treated cells. Expression of DNA repair genes, O(6)-methylguanine-DNA
      methyltransferase, poly(ADP-ribose) polymerase 1 and ligase 3 were reduced in
      lobarstin-treated cells. CONCLUSION: Enhanced sensitivity to temozolomide by
      lobarstin co-treatment may be attributed to reduced DNA repair.

PMID- 24324081
TI  - Antibody against tumor necrosis factor-alpha reduces bortezomib-induced allodynia
      in a rat model.
AB  - BACKGROUND: Bortezomib is an anti-neoplastic drug acting against multiple myeloma
      but its use is associated with the onset of painful peripheral neuropathy. Tumor
      necrosis factor-alpha (TNFalpha) is associated with the development of
      neuropathic pain; several models have shown that the inactivation of TNFalpha
      leads to a reduction in pain stimuli perception. The aim of the present study was
      to analyze if the administration of an antibody against TNFalpha is able to
      prevent the development of bortezomib-induced neuropathic pain. MATERIALS AND
      METHODS: Nerve conduction velocity was measured and a histopathological
      examination was performed to assess the extent of peripheral neuropathy. To study
      the onset of painful neuropathy, the response to mechanical or thermal stimuli
      was evaluated. RESULTS: This study demonstrated that co-administration of an
      antibody against TNFalpha is able to prevent allodynia induced by bortezomib but
      does not reduce neuropathy. CONCLUSION: Targeting TNFalpha might be useful in
      limiting patients' discomfort during bortezomib therapy.

PMID- 24324082
TI  - Epithelial-mesenchymal transition and cancer stem cells in endometrial cancer.
AB  - BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) and cancer stem cells
      (CSCs) are presumed to be key conditions for malignancy. Data concerning their
      role in endometrial cancer (EC) are scarce. We aimed to investigate the possible
      link between EMT and CSCs markers in EC samples. MATERIALS AND METHODS: The study
      encompassed 156 primary tumour samples. Using RT-qPCR, we analyzed the expression
      of EMT-related genes, SNAIL and SLUG, and the CSCs marker CD133. RESULTS: SNAIL
      and SLUG correlated with each other (R=0.33; p=0.00003). All the studied genes
      were expressed in both normal and malignant endometrial tissue. Decreased SNAIL
      expression was found to correlate with post-menopausal status (p=0.002).
      Decreased SLUG expression was associated with shorter overall survival (p=0.01).
      CONCLUSION: SLUG expression could serve as a prognostic factor in EC. No
      correlation between the expression of EMT and CSCs markers was found, suggesting
      there to be no association between the EMT and CSC phenotype in endometrial
      cancer.

PMID- 24324083
TI  - Advanced microtubular colorectal adenomas: a 10-year survey at a single hospital.
AB  - BACKGROUND: Colorectal carcinoma, the third most commonly diagnosed type of
      cancer in Europe and the USA, usually originates from colorectal adenoma (CRA).
      Three main histological phenotypes of CRA are usually recognized: tubular,
      villous and traditional serrated (TA, VA and TSA, respectively). In 1997, we
      reported a novel histological phenotype, the microtubular adenoma (MTA),
      epitomized by dysplastic epithelium arranged in closed rings (microtubules), with
      sideways-elongated outgrowth. MATERIALS AND METHODS: The material includes 4,446
      CRAs diagnosed at our Department during a 10-year period (2001-2010). RESULTS:
      Out of 4,446 CRAs, 68 (1.5%) were MTA; of these, 38 (55.9%) exhibited low-grade
      dysplasia (LGD), 17 (25.0%), high-grade-dysplasia, two (2.9%) intraepithelial
      carcinoma and three (4.4%), intramucosal carcinoma. Out of the 68 MTA, 22 (32.3%)
      were advanced MTA. Submucosal carcinoma (SMC) was present in eight (11.8%) MTAs.
      Ninety-four per cent (64/68) of the MTAs were left-sided adenomas. In previous
      work, we found that cell proliferation occurred in the dysplastic microtubules in
      MTA, initially in the luminal dysplastic epithelium in TA and VA, and initially
      at the bottom of the serrated dysplastic crypts in TSA. CONCLUSION: Due to these
      distinctive microscopic and cell proliferative attributes, a predominant left
      sided location and the absence of serrated configurations, it is submitted that
      MTA is a specific CRA phenotype, at variance with TA, VA, and TSA. The high
      frequency of SMC strongly suggests that MTA is an important alternative pathway
      in colorectal carcinogenesis.

PMID- 24324084
TI  - An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced
      NSCLC.
AB  - AIM: While meta-analyses and clinical trials show improved survival in advanced
      NSCLC treated with platinum-containing chemotherapy, there are few data
      concerning front-line platinum-free ifosfamide-based regimens. We aimed to
      compare cisplatin-based chemotherapy to ifosfamide-gemcitabine (IG) with pre
      defined second-line docetaxel. PATIENTS AND METHODS: 693 Untreated advanced
      inoperable NSCLC cases were randomised to either GIP (gemcitabine, ifosfamide,
      cisplatin), DP (docetaxel, cisplatin) or IG. Primary outcome was overall
      survival. RESULTS: Median age of the patients was 58 years with a predominance of
      males (75%), adenocarcinoma (56%), Karnofsky PS 80-100 (77%) and stage-IV disease
      (81%). Median survival times were 8.7, 8.8 and 8.3 months for IG, GIP and DP
      (p=0.79). GIP presented with (p<0.05) greater neutropenia, thrombopenia,
      vomiting, while greater cardiotoxicity, diarrhea, peripheral neuropathy were
      observed for DP and encephalopathy for IG. CONCLUSION: In advanced NSCLC,
      cisplatin-based CT is not superior to a platinum-free regimen (ifosfamide
      gemcitabine) with a favourable toxicity profile.

PMID- 24324085
TI  - Levels of circulating polychlorinated biphenyls and mammographic breast density.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous chemicals found in
      the environment that accumulate in body fat and exhibit endocrine-disrupting
      properties. These compounds are therefore suspected of influencing breast cancer
      risk, but results from studies are inconsistent. To further clarify the role of
      PCBs in the etiology of breast cancer, the present study aimed to examine the
      relation of 24 PCB congener levels, which were considered individually and in
      combinations, with mammographic density, one of the risk factors most strongly
      associated with breast cancer. MATERIALS AND METHODS: Plasma PCB levels were
      measured by gas chromatography coupled to mass spectrometry in 106 post
      menopausal women for whom mammographic density was measured using a computer
      assisted method. RESULTS: Spearman correlation coefficients adjusted for
      potentially confounding factors (rs) show that while levels of total PCBs do not
      appear to be correlated with the percentage mammographic density (rs=-0.19,
      p=0.08), an increase in the plasma levels of congeners nos. 153, 183, 196 and
      combined Wolff group 3 PCBs is negatively correlated with the percentage
      mammographic density (rs=-0.24, p=0.03; rs=-0.30, p=0.004; rs=-0.22, p=0.04; and
      rs=-0.22, p=0.04 respectively). CONCLUSION: Our results suggest that an increase
      in the plasma levels of some PCB congeners, in particular cytochrome P450 1A1
      inducers, is associated with lower mammographic density in post-menopausal women.

PMID- 24324086
TI  - Disease outcome of patients with pancreatic cancer in a cohort treated outside
      clinical trials.
AB  - This retrospective study included 92 consecutive patients with locally advanced
      or metastatic pancreatic cancer treated in the Turku University Hospital in 2010.
      The diagnosis of pancreatic cancer was verified by either histological samples
      (adenocarcinoma) or by imaging or both, excluding other known histological types
      of tumours. Median patient survival was 11 months. Smokers had a better median
      overall survival (20 months) than non-smokers (10 months) (p=0.029). Patients
      with carcinoma of the head of pancreas had the best survival rates (15 months),
      whereas those with cancers of the tail of pancreas reached a median survival of
      only 3 months. The importance of this small trial resides in its retrospective
      and non-randomized nature, analyzing real-life patients, as encountered in daily
      practice, out of which, unfortunately, a substantial proportion would not be
      eligible for any randomized clinical trial. 

PMID- 24324087
TI  - Wilms' Tumor Gene 1 (WT1)--loaded dendritic cell immunotherapy in patients with
      uterine tumors: a phase I/II clinical trial.
AB  - AIM: Treatment options are limited in uterine cancer, leading to a poor
      prognosis. Overexpression of Wilms' tumor gene 1 (WT1), the highest ranked tumor
      antigen, is attractive for immunotherapy. PATIENTS AND METHODS: Six pre-treated
      patients with uterine cancer received four weekly vaccines of autologous
      dendritic cells (DCs) electroporated with WT1 mRNA. Safety, feasibility and
      immunogenicity were assessed. In cases of response, patients received monthly
      booster vaccines. RESULTS: The technique was feasible. One patient had a local
      allergic reaction. Three out of four Human Leucocyte Antigen-A2 (HLA-A2)-positive
      patients showed an oncological response; an enrichment of WT1-specific T-cells
      was observed in two of them. Two HLA-A2-negative patients did not show an
      oncological or an immunological response. CONCLUSION: A first series of six
      patients with uterine cancer treated with WT1 mRNA-electroporated DCs is
      presented herein. Oncological and immunological responses were observed and are
      supportive for further research.

PMID- 24324088
TI  - Factors predictive of oncological outcome after nephroureterectomy: comparison
      between laparoscopic and open procedures.
AB  - BACKGROUND: Although laparoscopic radical nephroureterectomy is the standard
      treatment for localized upper urinary tract urothelial carcinoma, open radical
      nephroureterectomy has been reported to have a different rate of intravesical
      recurrence. PATIENTS AND METHODS: Intravesical recurrence-free, progression-free,
      and overall survival rates among patients undergoing open and laparoscopic
      radical nephroureterectomy from 2002 to 2013 were analyzed. RESULTS: Although no
      single factor predicted intravesical recurrence-free survival, a past history of
      bladder cancer or grade 3 was related to poorer intravesical recurrence-free
      survival rate in patients treated with laparoscopic radical nephroureterectomy.
      Moreover, the novel proposed risk classification based on our data clearly showed
      better progression-free survival and overall survival, as well as intravesical
      recurrence-free survival, in patients treated with laparoscopic radical
      nephroureterectomy. CONCLUSION: The findings reported here may help urologists
      predict oncological outcomes and to plan follow-up schedules after laparoscopic
      radical nephroureterectomy.

PMID- 24324089
TI  - Exceptionally high incidence of grade 2-3 late rectal toxicity in patients with
      prostate cancer receiving hypofractionated (2.2 Gy) soft tissue-matched image
      guided intensity-modulated radiotherapy.
AB  - AIM: To evaluate the incidence of rectal toxicity in patients undergoing
      hypofractionated (2.2 Gy) image-guided intensity-modulated radiotherapy (IG-IMRT)
      for prostate cancer. PATIENTS AND METHODS: We examined 117 consecutive patients
      with prostate cancer who underwent IG-IMRT from June 2007 to July 2009. The
      median follow-up time was 32 months (range 20-42 months). The clinical target
      volume (CTV) consisted of the prostate and seminal vesicles, and the planning
      target volume (PTV) consisted of the CTV plus a 5-mm expansion, not avoiding the
      rectum. The PTV received a dose of 72.6-74.8 Gy in 33-34 fractions (2.2
      Gy/fraction). Megavoltage computed tomographic (MVCT) scans were performed before
      each treatment and corrected to the registered position for planning CT scans
      using prostate soft tissue matching. RESULTS: Late rectal bleeding of grades 1,
      2, and 3 (Common Terminology Criteria for Adverse Events v3.0) occurred in 19
      (16%), five (4%), and four (3%) patients, respectively. Late urinary toxicities
      of grades 1 and 2 occurred in five (4.3%) and eight (6.8%) patients,
      respectively. We found a paradoxically increased risk of rectal bleeding with
      more accurate irradiation of the rectum using soft tissue matching, whereas only
      a small percentage was reported in other IMRT series. CONCLUSION: IG-IMRT using
      daily MVCT scans allowed for exact dose delivery, which resulted in an increased
      rectal dose and exceptionally high incidence of rectal toxicity. Therefore,
      careful PTV contouring and dose schedule settings are important for safe
      administration of IG-IMRT.

PMID- 24324090
TI  - Long-term outcome of seropositive HIV patients with head and neck squamous cell
      carcinoma treated with radiation therapy and chemotherapy.
AB  - AIM: To report the outcome of radiation therapy (RT) +/- chemotherapy in HIV
      seropositive patients with Head and Neck Squamous Cell Carcinoma (HNSCC).
      PATIENTS AND METHODS: This is the largest single-Institution retrospective study
      to date, consisting of 73 HIV patients with HNSCC treated from January 1997-2010.
      The median age at RT, HIV diagnosis and the duration of patients being HIV
      seropositive were 51, 34, and 11 years, respectively. Seventy patients had SCC
      and one had submandibular salivary duct carcinoma. Stages I-II, III and IVA/B
      were: 22%, 27% and 51%, respectively. Primary cancer sites comprised the larynx
      (37%), oropharynx (32%), oral cavity (13%), hypopharynx (7%), nasopharynx (4%),
      unknown primary (MUP) (4%), nasal cavity (3%), and submandibular salivary duct
      (1%). All patients had an ECOG performance scale of <=1 and were treated with RT
      +/- chemotherapy. Fifty patients (70%) were on highly active anti-retroviral
      therapy (HAART) during treatment, and the median CD4 count was 290 (range: 203
      1142). Median dose of 70, 63, and 54 Gy were delivered to the gross disease, high
      risk neck, and low-risk neck respectively. Median duration of treatment was 52
      (range: 49-64) days. Twelve patients (17%) underwent neck dissection for N3
      disease. RESULTS: After a median follow-up of 47 months (range: 7-140), the 4
      year locoregional control (LRC) and overall survival (OS) were 69% and 55%
      respectively. Seven patients (10%) developed second primary sites within the
      first 5 years of completing RT (2 anal SCCs and 5 HNSCCs). The LRC for Stages
      III/IV larynx and oropharynx SCC (which represent the majority of the cohort)
      were 76% and 70%, respectively. Chemo/RT-related late toxicities were dysphagia
      of grade<=2, 3, and 4 found in 74%, 15% and 11% of patients, respectively.
      Hoarseness (grade 1) was reported in 10% of patients; no patient experienced
      grade >=2. Xerostomia grade <=2, and 3 was found in 77% and 23% of patients,
      respectively. A Chi-square test and univariate analysis showed statistically
      significant relationships between LRC and duration of RT (p<0.001), as well as
      positive trends for weight loss (<10%) and absence of second malignancy.
      CONCLUSION: Definitive RT +/- chemotherapy for HIV-seropositive patients with
      HNSCC appears to be less effective compared to the observed rates of LRC and OS
      of other HNSCC without HIV. Due to advances in the HAART which prolongs HIV
      patients' survival, it is extremely important to establish better treatment
      strategies to improve therapeutic ratio in this growing patient population.

PMID- 24324091
TI  - YKL-40 and mesothelin in the blood of patients with malignant mesothelioma, lung
      cancer and asbestosis.
AB  - BACKGROUND/AIM: In the diagnosis of malignant mesothelioma (MM) there still is a
      lack of specific and sensitive screening biomarkers: this study examined the
      discriminatory power of a panel of serum/plasma biomarkers. PATIENTS AND METHODS:
      The study involved four groups: (a) individuals previously exposed to asbestos
      with asbestosis; (b) patients with MM; (c) patients with non-small cell lung
      cancer; and (d) controls without any evidence of malignancy. The concentrations
      of mesothelin, chitinase-3-like-1 (YKL-40), vascular endothelial growth factor
      (VEGF), endothelin-1, interleukin-8 (IL-8) and fibulin-3 in the serum of patients
      were determined. RESULTS: Patients with MM had significantly higher serum levels
      of mesothelin (p<0.001), YKL-40 (p<0.001), IL-8 (p<0.001) and VEGF (p<0.01) than
      controls. The cut-off point for MM was 1.26 nM for mesothelin alone, and 167
      pg/ml for YKL-40 alone; the presence of both markers above these cut-off levels
      improved diagnostic specificity. CONCLUSION: The addition of YKL-40 may improve
      the specificity of mesothelin measurements alone for detecting patients with MM.

PMID- 24324092
TI  - The need for repeated urological evaluation in low-risk patients with microscopic
      hematuria after negative diagnostic work-up.
AB  - AIM: To evaluate the role of repeated urological evaluation after negative
      initial diagnostic work-up of asymptomatic microhematuria (AMH) in low-risk
      patients. PATIENTS AND METHODS: Criteria for patient inclusion were a complete
      negative initial diagnostic assessment including ultrasound (US), cystoscopy,
      upper urinary tract (UUT) imaging using intravenous urography (IVU) or
      multiphasic computed tomography (CT), absence of risk factors and a follow-up
      period of at least three years. Based on our institutional practice, urinalysis
      was repeated yearly; cystoscopy with US was repeated three years after initial
      work-up. The oncological outcome was evaluated across a mean follow-up of 8
      (range: 3.7-10.2) years. RESULTS: A case series of 87 (32.2% of 270) low-risk
      patients, 56 women and 31 men, with a mean age of 52.4 (range: 19-87) years was
      studied. Three years after initial work-up, cystoscopy confirmed no bladder
      carcinoma in any of these 87 patients. Prostate cancer was diagnosed in one
      (1.1%) patient. In five (5.6%) patients, nephrological evaluation due to
      concomitant proteinuria on follow-up demonstrated chronic renal insufficiency
      (n=3), IgA nephropathy (n=1) and papillary necrosis of the kidney (n=1).
      CONCLUSION: Low-risk patients with persistent AMH after negative urological
      evaluation have a neglectable risk of developing bladder cancer on follow-up.
      Newly-discovered proteinuria on follow-up should be clarified by a nephrologist,
      as proteinuria could be a sign of significant glomerular disease.

PMID- 24324093
TI  - Gemcitabine for the treatment of classic Kaposi's Sarcoma: a case series.
AB  - Radiation-refractory and progressive Kaposi's sarcoma remains a challenge for the
      oncologist. Systemic chemotherapy has improved, but results are poor. Gemcitabine
      is largely employed in oncology for its high therapeutic rates. We report four
      cases of patients with radiation-refractory and progressive classic Kaposi's
      sarcoma, two of whom were pre-treated with chemotherapy and then underwent
      treatment with gemcitabine. All patients had an objective response with long
      progression-free survival. Gemcitabine seems to be very effective and safe in the
      treatment of classic Kaposi's sarcoma. 

PMID- 24324094
TI  - Phase II trial of pemetrexed continuation--maintenance after carboplatin-based
      induction in untreated non-squamous non-small cell lung cancer.
AB  - AIM: We conducted a phase II study to evaluate the efficacy and safety of
      pemetrexed continuation-maintenance after carboplatin-based induction for
      advanced non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Thirty-four patients with advanced or recurrent non-squamous NSCLC received
      carboplatin (area under the concentration-time curve 6 mg/ml*min) plus pemetrexed
      (500 mg/m(2)) on day 1 tri-weekly. After four cycles of induction, patients
      without disease progression received pemetrexed maintenance until disease
      progression or unacceptable toxicity. RESULTS: Twenty-five patients completed
      induction and 22 received maintenance. The 1-year survival, objective response
      and disease control rates were 70.3%, 32.4% and 88.2%, respectively. The median
      progression-free survival and overall survival of all patients were 5.2 and 23.3
      months. The incidental rates of grade 3 or more severe adverse events were low.
      CONCLUSION: This regimen appears to be an appropriate option for chemonaive
      patients with advanced non-squamous NSCLC.

PMID- 24324096
TI  - Improvement of adherence to guidelines for antiemetic medication enhances emetic
      control in patients with colorectal cancer receiving chemotherapy of moderate
      emetic risk.
AB  - Prevention of chemotherapy-induced nausea and vomiting (CINV) according to the
      clinical practice guidelines is particularly important. In the present study, we
      investigated the adherence to the guidelines for antiemetic medication and the
      control of CINV in 61 patients with colorectal cancer receiving the first course
      of chemotherapy of moderate emetic risk at our outpatient cancer chemotherapy
      clinic. Furthermore, we carried out intervention to improve evidence-based
      antiemetic medication in another 64 patients. The rate of adherence to the
      antiemetic guidelines was only 6.6%; non-adherence was due mostly to the lack of
      dexamethasone treatment on days 2 and 3. In the interventional group, antiemetic
      medication adherence was markedly enhanced to 89%, which led to a significant
      enhancement of complete protection from nausea and vomiting during-delayed period
      (days 2-5 after chemotherapy) from 54% to 74% (p<0.05), although the daily dose
      of dexamethasone was 4 mg, lower than that recommended by the guidelines (8 mg).
      Finally, we evaluated the effect of dexamethasone at a daily dose of 4 mg, since
      little is known about the efficacy of such dose. Dexamethasone at this dose was
      found to be effective at elevating the rate of complete protection from nausea
      and vomiting during-delayed period (increase of 20%, p<0.05). These findings
      suggest that medication intervention to reduce the gap between guidelines and
      clinical practice improves the emetic control in patients with colorectal cancer
      receiving moderately-emetic chemotherapy. 

PMID- 24324095
TI  - Quality of life assessment in Taiwanese patients with bone metastases from breast
      cancer receiving zoledronic acid.
AB  - BACKGROUND: The current study aimed to examine the impact of zoledronic acid
      therapy on health-related quality of life (HRQoL) in Taiwanese patients with bone
      metastases from breast cancer. PATIENTS AND METHODS: Patients with bone
      metastases from breast cancer who received zoledronic acid according to the
      standards of care were enrolled in this observational phase IV study. HRQoL was
      measured monthly using the European Organization for Research and Treatment of
      Cancer Quality of Life Core Questionnaire 30 (QLQ-C30) and the breast cancer
      specific module (BR-23) for 24 months. RESULTS: A total of 366 patients from 13
      centers were enrolled. QLQ C-30 demonstrated that zoledronic acid improved the
      HRQoL in different aspects. In particular, a significant reduction of pain in the
      first 14 months and the 22-month follow-up was reported by patients. QLQ-BR23
      indicated improved future perspective and breast symptom scores over the course
      of the study. CONCLUSION: These data confirm the HRQoL benefits and safety of
      zoledronic acid in Taiwanese patients with bone metastases from breast cancer.

PMID- 24324097
TI  - Octreotide acetate-steroid combination therapy for malignant gastrointestinal
      obstruction.
AB  - AIM: The Aim of this study was to investigate improvements in symptoms caused by
      gastrointestinal obstruction following administration of octreotide acetate
      (Sandostatin(r)) injection through steroid and opioid administration. PATIENTS
      AND METHODS: Patients (n=37) hospitalized with malignant gastrointestinal
      obstruction were enrolled in the present study. Twenty seven of them were
      investigated for gastrointestinal symptoms using the Japanese version of the
      Support Team Assessment Schedule (STAS-J). RESULTS: Octreotide acetate was
      administered intravenously to all 27 patients. Out of them, 17 showed a marked
      response, four a good response, and six no response. The overall response rate
      was 77.8%. Octreotide acetate with a steroid was administered to 19 patients; 13
      showed a marked response, four a good response, and two no response at all.
      Multiple logistic regression analysis showed that that steroid administration
      improved the efficacy of octreotide acetate after adjusting for infusion dose
      (p=0.03). CONCLUSION: Intravenous administration of octreotide acetate with
      steroid can effectively improve gastrointestinal symptoms due to malignant
      gastrointestinal obstruction without adverse events.

PMID- 24324098
TI  - Non-surgical multimodality treatment for locally advanced (T3-4) hypopharyngeal
      cancer: the impact of pre-treatment hemoglobin level.
AB  - AIM: To examine the role of a non-surgical multimodality approach in patients
      with locally advanced pharyngeal cancer who refuse surgery or are inoperable.
      PATIENTS AND METHODS: Between 2006 and 2011, 19 patients with T3-4 hypopharyngeal
      cancer received multimodality non-surgical treatment. Out of these patients, nine
      refused surgery, and nine were inoperable. Their age range was 52-86 years
      (median, 68 years). Ten patients had T3, and 9 had T4 (two with stage III and 17
      with stage IV). Neoadjuvant induction chemotherapy was administered in 11
      patients. Hyperthermia was performed in patients with advanced lymph node
      metastasis. Radiotherapy was administered at a median of 61 Gy (60-61.2 Gy) in
      conventional fractionation. Concurrent chemotherapy was administered to all
      patients: through intra-arterial infusion in seven, systemic infusion in 10, or
      both in two. Median follow-up time was 27 months (range: 6-50 months). RESULTS:
      At the primary site, 16 patients (84%) achieved a complete response and three
      (16%) with partial response, resulting in a 100% response rate. Locoregional
      failure appeared in the form of six local and two regional lesions, and in one
      case in both types of lesions. Three-year local control, disease-free and overall
      survival rates, and laryngeal preservation rates were 65%, 48%, 50%, and 83%,
      respectively. Anemia was the only strong predisposing factor, not only for
      reduced local control but also for reduced progression-free and overall survival
      rates. Acute toxicities of grade 3 or more included hematological toxicity in
      four patients, gastrointestinal toxicity in two, and pneumonia in 6. Late adverse
      reaction of dysphagia grade 3 was found in one patient, whereas dysphagia grade 4
      was not observed. CONCLUSION: Multimodality non-surgical treatment could be a
      useful option for patients who refuse surgery and have inoperable disease with
      substantial curative potential without severe adverse reactions.

PMID- 24324099
TI  - Prognostic value of preoperative inflammation-based prognostic scores in patients
      with stage IV colorectal cancer who undergo palliative resection of asymptomatic
      primary tumors.
AB  - BACKGROUND: The need for palliative resection of asymptomatic primary tumor in
      patients with unresectable metastatic colorectal cancer (CRC) is still
      controversial. In order to identify predictors of survival after palliative
      resection, we investigated the correlations between clinicopathological factors,
      preoperative Glasgow prognostic score (GPS) and neutrophil-to-lymphocyte ratio
      (NLR), and survival. PATIENTS AND METHODS: A total of 94 patients were enrolled
      in the present study. The prognostic value of the clinicopathological factors,
      GPS and NLR were analyzed retrospectively. RESULTS: A multivariate analysis
      revealed that both the GPS and NLR were independent predictors of survival along
      with the preoperative Eastern Cooperative Oncology Group performance status (PS)
      and extent of distant metastasis. We classified the patients using a combination
      of these factors, and categorized them into three risk groups. The median
      survival time was five months in the high-risk group, compared to 21.5 months in
      the intermediate-risk group and 37 months in the low-risk group. CONCLUSION: Sub
      classification based on the GPS, NLR, PS and extent of distant metastasis can
      classify patients into three independent groups. There may be no survival
      benefits associated with palliative resection in the high-risk group.

PMID- 24324100
TI  - Radiotherapy for early-stage primary ocular adnexal mucosa-associated lymphoid
      tissue lymphoma.
AB  - BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma
      (POAML) is a rare disease. The purpose of this study was to evaluate the
      treatment outcome and patterns of failure of patients with early-stage POAML
      treated with radiotherapy. PATIENTS AND METHODS: From 1995 to 2008, 53 patients
      with early-stage POAML were reviewed. Tumors were categorized as either
      superficial or mass-forming type. In principle, superficial lesions (n=11) were
      treated with 24 Gy, while the mass-forming lesions (n=42) were irradiated with 30
      Gy. The median follow-up period was 3.9 years. RESULTS: All four cases of relapse
      had mass-forming lesions. The 5-year overall and progression-free survival rates
      were 100% and 91.5%, respectively. Although 30 patients experienced grade 2 or 3
      late adverse events, no patients had radiation-related retinopathy. CONCLUSION:
      Early-stage POAML can be well-controlled with radiotherapy. However, the risk of
      distant relapse should be noted, in particular, for mass-forming tumors.

PMID- 24324101
TI  - Usefulness of 18F-fluorodeoxyglucose positron emission tomography as predictor of
      distant metastasis in preoperative carbon-ion radiotherapy for pancreatic cancer.
AB  - AIM: The purpose of this study was to evaluate the role of FDG-PET regarding the
      indication of preoperative carbon-ion radiotherapy (CIRT) for pancreatic cancer
      patients. PATIENTS AND METHODS: Patients with resectable pancreatic cancer
      underwent preoperative CIRT. The impact of baseline SUVmax on prognosis for
      patients was assessed by analyzing correlations with distant metastasis-free
      survival (DMFS) and overall survival (OS). RESULTS: Out of 21 patients, local
      recurrence was observed in no patient and distant metastasis was found in 13
      patients (62%). 1-year DMFS and OS in low-SUVmax group were significantly higher
      than those in high-SUVmax group (91% vs. 20% and 91% vs. 56%). SUVmax was
      significantly correlated with DMFS and OS. CONCLUSION: Our data indicated a
      significant correlation between SUVmax and DMFS. FDG-PET might be useful for
      determining the indication of preoperative short-course CIRT for patients with
      resectable pancreatic cancer.

PMID- 24324102
TI  - Adjuvant hepatic arterial infusion chemotherapy with 5-Fluorouracil and
      interferon after curative resection of hepatocellular carcinoma: a preliminary
      report.
AB  - BACKGROUND AND AIM: Advanced hepatocellular carcinoma (HCC) with portal vein
      invasion or intrahepatic metastases has an unfavorable prognosis, even after
      curative hepatic resection. The aim of the present study was to evaluate the
      efficacy of adjuvant hepatic arterial infusion chemotherapy with 5-fluorouracil
      (5-FU) and systemic interferon (IFN). PATIENTS AND METHODS: Patients who were
      diagnosed as having HCC with portal vein invasion or intrahepatic metastases were
      included in the study (n=33). Out of these patients, 16 were treated with
      adjuvant therapy consisting of continuous arterial infusion of 5-FU and
      subcutaneous injection of IFN-alpha. Another 17 patients who underwent hepatic
      resection without adjuvant chemotherapy served as controls. RESULTS: The five
      year cumulative survival rate was significantly higher in the adjuvant treatment
      group (71.1%) than in the control group (44.0%; p=0.023). The rate of patients
      with multiple (>=4) recurrent intrahepatic nodules was significantly lower in the
      adjuvant group (44.4%) than in the control group (100%; p=0.040). The development
      of intrahepatic recurrence within 12 months was significantly lower in the
      adjuvant group (33.3%) than in the control group (80.0%; p=0.040). CONCLUSION:
      Our data suggest that this adjuvant chemotherapy can improve postoperative
      prognosis by reducing intrahepatic recurrence.

PMID- 24324103
TI  - C-reactive protein as a significant prognostic factor for stage IV gastric cancer
      patients.
AB  - BACKGROUND/AIM: We aimed to clarify the roles of CRP and albumin as independent
      prognostic factors for stage IV gastric cancer (stIVGC) patients. The optimal cut
      off value for these two markers was investigated. PATIENTS AND METHODS: 123
      stIVGC patients presented at our Medical Center from April, 2005 to March, 2011
      were investigated. Clinicopathological, tumor-specific and treatment factors were
      analyzed. Univariate and multivariate Cox proportional regression models were
      used to identify for favorable factors affecting overall survival. The Receiver
      operating characteristic (ROC) curve was utilized to determine cut-off values.
      RESULTS: Multivariate analysis revealed CRP (hazard ratio (HR): 1.11; 95%
      confidence interval (CI): 1.03-1.18) to be an independent prognostic factor for
      survival. According to the results of the analysis albumin was excluded. ROC
      curve of the 3-month-prognosis patients revealed a maximum area under the curve
      of 0.85 and a cut-off value of 1.7 mg/dl. CONCLUSION: CRP can be considered an
      independent prognostic factor for survival of stIVGC patients and can be used for
      short-term survival prediction.

PMID- 24324104
TI  - Chemotherapy followed by surgery on the basis of biomarker examination for
      patients with advanced non-small cell lung cancer.
AB  - BACKGROUND/AIM: We have previously reported that low expression of excision
      repair cross-complementing-1 (ERCC1), class III beta-tubulin (tubulin),
      thymidylate synthase (TYMS) and ribonucleotide reductase-M1 (RRM1) is indicative
      of a favorable prognosis in patients with c-N2,3 non-small cell lung cancer
      (NSCLC) treated with surgery after induction chemoradiotherapy. In the present
      study, we prospectively explored the tailor-made treatment menu for induction
      chemotherapy according to the status of biomarkers, and evaluated the biomarker
      status pre- and post-chemotherapy. PATIENTS AND METHODS: Twenty-five patients
      with pathologically-proven NSCLC who were not appropriate candidates for initial
      surgery were enrolled (October 2010 to June 2012, stage IIIA/B/IV1a/1b;14/5/2/4
      respectively). Immunohistochemistry was performed to evaluate intratumoral
      expression of biomarkers. Epidermal growth factor receptor (EGFR) mutation was
      evaluated by direct sequencing. Two to four cycles of chemotherapy were performed
      with or without concurrent radiation (50 Gy). RESULTS: Docetaxel (n=12),
      pemetrexed (n=4), S-1 (n=4), docetaxel-plus-bevacizumab (n=3), and pemetrexed
      plus-bevacizumab (n=2), in combination with platinum were selected for the
      therapeutic regimen. Twenty-one (84.0%) patients exhibited good partial response,
      and underwent complete resection without major morbidity or mortality. Of these
      21 patients, four achieved a pathologically-complete response (PCR), and 10
      achieved a major pathological response. The 3-year overall survival rate was
      58.7% for the 25 patients overall, and the 2-year overall survival rate was 73.6%
      for patients who underwent surgery. Among the 17 patients who underwent resection
      (except for four with PCR), the status of ERCC1, tubulin, TYMS, RRM1 and EGFR
      changed markedly after chemotherapy in six patients, eleven patients, eight
      patients, nine patients and one patient, respectively. CONCLUSION: Chemotherapy
      followed by surgery on the basis of biomarker examination is a challenging
      approach for patients with advanced NSCLC who otherwise have poor outcomes. Post
      chemotherapy biomarker status changed markedly in many cases.

PMID- 24324105
TI  - Efficacy of transcatheter arterial chemoembolization with miriplatin-lipiodol
      water-soluble contrast agent emulsion in patients with hepatocellular carcinoma.
AB  - AIM: To evaluate the therapeutic efficacy of transcatheter arterial
      chemoembolization (TACE) using miriplatin emulsion in unresectable hepatocellular
      carcinoma (HCC). PATIENTS AND METHODS: The efficacy of TACE was evaluated by
      dynamic computed tomography or magnetic resonance imaging three months after
      TACE, according to the Response Evaluation Criteria in Cancer Study Group of
      Japan (RECICL). Adverse events were assessed using Common Terminology Criteria,
      version 4.0. RESULTS: Eighteen patients with 48 lesions received TACE with
      miriplatin-lipiodol (LPD) suspension (miriplatin suspension) and 53 patients with
      114 HCC tumors received TACE with miriplatin-LPD water-soluble contrast agent
      emulsion (miriplatin emulsion). TACE with miriplatin emulsion enabled for
      administration of a higher dose of miriplatin compared to TACE with miriplatin
      suspension (p=0.016), although there were no significant differences in the
      frequency of adverse events between the two groups. The treatment effect per
      tumor was significantly higher in the emulsion group than in the suspension group
      (p=0.001). The time-to-progression per tumor was significantly shorter in the
      suspension group than in the emulsion group (p=0.001). CONCLUSION: TACE with
      miriplatin emulsion is more effective than that with miriplatin suspension.

PMID- 24324106
TI  - Immunopositivity of Beclin-1 and ATG5 as indicators of survival and disease
      recurrence in oral squamous cell carcinoma.
AB  - AIM: To evaluate the expression and prognostic value of two autophagy-related
      (Atg) proteins, Beclin-1 and Atg5, in human oral squamous cell carcinoma (OSCC)
      and to correlate findings with clinical outcomes. PATIENTS AND METHODS:
      Immunohistochemistry for Beclin-1 and Atg5 was assessed in tumor specimens from
      90 patients with OSCC. Immunopositivity was semi-quantitatively scored and
      receiver-operating characteristic curve analysis was used to determine the cut
      off positivity score. RESULTS: 55 (61.1%) and 52 (57.8%) cases showed positive
      Beclin-1 and Atg5 staining, respectively. 40 tumors (44.4%) were positive for
      both Beclin-1 and Atg5 expression and 23 cases (25.6%) showed absence of both
      proteins. Beclin-1 expression significantly correlated with tumor grade (p=0.008)
      and lymph node metastasis (p=0.009). The expression of Atg5 was associated with
      tumor grade (p=0.016), advanced clinical stage (p<0.001), large tumor size
      (p=0.002), and lymph node metastasis (p<0.001). A significant difference in 3
      year OS (p=0.050) and TTR (p=0.049) between the patients with Beclin-1 expression
      and those not showing Beclin-1 expression was found whereas the difference did
      not reach a statistical significance for Atg5 expression. 3-year OS and TTR
      differed significantly between patients with dual expression and those with
      double-negative expression (p=0.022 and p=0.026, respectively). CONCLUSION: Dual
      expression of tumor Beclin-1 and Atg5 expression may be an adverse prognostic
      indicator for OSCC.

PMID- 24324107
TI  - Association of GSTP1 methylation with aggressive phenotype in ER-positive breast
      cancer.
AB  - AIM: We investigated the association of glutathione S-transferase P1 (GSTP1)
      expression and methylation status with clinicopathological characteristics of
      estrogen receptor (ER)-positive breast cancers. MATERIALS AND METHODS: Primary ER
      positive breast cancer patients (n=177, stage I-III) were retrospectively
      analyzed. A quantitative GSTP1 methylation assay was performed using DNA micro
      dissected from formalin-fixed and paraffin-embedded (FFPE) breast surgical
      specimens and GSTP1 expression was examined immunohistochemically. RESULTS: GSTP1
      methylation index (MI) was higher for the following patient subsets: Large-size
      (p=0.029), high-grade (p=0.010), human epidermal growth factor receptor-2 (HER2)
      positive (p=0.024) and Ki67-positive (p=0.001) patients. In addition, GSTP1 hyper
      methylation was more frequently observed in the luminal-B than the luminal-A
      subtype (p<0.001) and there was no significant difference in GSTP1 positivity
      between the two subtypes (p=0.150). CONCLUSION: GSTP1 methylation may well be
      associated with the pathogenesis of the biologically-aggressive phenotype in ER
      positive breast cancer.

PMID- 24324108
TI  - Long-term outcome in patients with recurrent malignant glioma treated with
      Perillyl alcohol inhalation.
AB  - AIM: This retrospective study aimed to evaluate the long-term response and
      toxicity of recurrent malignant glioma patients to inhalation chemotherapy with
      perillyl alcohol (POH). PATIENTS AND METHODS: The cohort included 117 men and 81
      women with primary glioblastoma multiforme (GBM; n=154), grade III astrocytoma
      (AA; n=26) and anaplastic oligodendroglioma (AO; n=5). POH inhalation schedule 4
      times daily started with 66.7 mg/dose; 266 mg/day and escalated up to 133.4
      mg/dose; 533.6 mg/day. Clinical toxicity and overall survival following treatment
      were compared with tumor size, topography, extent of peritumoral edema and
      histological classification. RESULTS: Adhesion to the protocol was high (>95%),
      POH (533.6 mg/daily) occasionally caused nose soreness but rarely nosebleed.
      Tumor size, peritumoral edema and the oligodendroglial component influenced
      response to treatment. CONCLUSION: After 4 years under exclusive POH treatment,
      19% of patients still remain in clinical remission. Long-term POH inhalation
      chemotherapy is a safe and non-invasive strategy efficient for recurrent
      malignant glioma.

PMID- 24324109
TI  - Analytical and clinical performance of Kroma iT, a compact fully-automated
      immunochemistry analyzer for fecal occult hemoglobin.
AB  - BACKGROUND: We performed a laboratory and clinical evaluation of Kroma iT (Linear
      Chemicals S.L), an immunoturbidimetric analyzer for the detection of fecal occult
      blood. MATERIALS AND METHODS: After a familiarization period, the imprecision,
      linearity of dilution and carry-over were determined and a clinical evaluation
      was performed on 210 patients. RESULTS: Within-run imprecision ranged between
      1.06% and 8.04%. Between-run imprecision ranged between 3.11% and 13.09%.
      Linearity of dilution revealed a mean recovery of all dilutions of 95.24%, with a
      standard deviation of 7.47%. No carry-over was detected. The clinical evaluation
      demonstrated that the mean hemoglobin levels of the fecal immunochemical test
      values from patients with advanced neoplasms (colorectal cancer plus advanced
      adenoma) were significantly higher than those of cases with a normal colonoscopy
      examination. Sensitivity for advanced neoplasms at cut-off values between 80 and
      300 ng/ml (6.4-24 mg Hb/Kg feces) ranged from 45.5% to 36.4% and the specificity
      ranged from 86.8% to 92.3%. The positive predictive values for detecting
      colorectal cancer and advanced adenomas were 5.4-6.4% and 27-34% respectively and
      the negative predictive value ranged from 92.5% to 91.7%. Using two samples per
      patient, a substantial increase of sensitivity was observed, with only a slight
      decrease in specificity. CONCLUSION: Kroma iT analyzer is easy to handle and safe
      for personnel to use. Its analytical and clinical performance makes it suitable
      for use in a clinical chemistry laboratory for the early detection of advanced
      neoplasms.

PMID- 24324110
TI  - Cancer treatment of severely-III patients not eligible for chemotherapy.
AB  - BACKGROUND: Despite having disseminated cancer, not all patients are eligible for
      palliative chemotherapy or targeted therapies. AIM: To study reasons for
      withholding palliative chemotherapy, to survey which alternatives were offered
      and to study survival outcomes. MATERIALS AND METHODS: Medical records of 346
      patients with disseminated cancer were collected. Univariate and multivariate
      statistics were applied. RESULTS: In total, 48% (n=164) of patients were not
      offered palliative chemotherapy, mainly depending on diagnosis, age and
      performance status. Instead, palliative radiotherapy (44%) or endocrine
      treatments (25%) (breast and prostate cancer) were prescribed. The mean survival
      for these patients was 216 days, with median survival of only 77 days. In the Cox
      multivariate analysis survival, prospects were better if the patient was
      ambulatory and living at home at the first consultation (p<0.01), if performance
      status was acceptable (p<0.01) and if endocrine treatment was an option (p<0.05).
      CONCLUSION: The prognosis is quite variable, even in cases where palliative
      chemotherapy is not an option. A hormone-sensitive tumour and a good performance
      status are significant factors affecting survival in this patient group.

PMID- 24324111
TI  - Patients with brain metastases from colorectal cancer are not condemned.
AB  - BACKGROUND: Brain metastases (BMs) from colorectal cancer are rare (2-3%). They
      usually occur in advanced stages of the disease and their prognosis is poor. The
      aim of this study was to assess the impact of surgical resection of BMs from
      colorectal cancer in terms of overall survival. PATIENTS AND METHODS: A
      retrospective bi-centric study included all patients with resected BMs from
      primary colorectal adenocarcinoma from 1998 to 2009. RESULTS: Twenty-eight
      patients [13 males, median: 62 (range: 44-86) years old) were included. Fifteen
      patients presented with other metastatic sites (lung, liver). BMs were
      metachronous in 16/28 (57%) of patients [median: 19 months (range: 7-97)]. Median
      overall survival reached 12 months. Brain recurrences occurred in 32% of patients
      and were treated by curative intent in 5/9 cases. CONCLUSION: When indicated, an
      aggressive management based on surgical resection of BMs from colorectal cancer,
      must be performed, in order to improve overall survival to at least 12 months.

PMID- 24324112
TI  - Definitive fractionated re-irradiation for local recurrence following
      stereotactic body radiotherapy for primary lung cancer.
AB  - AIM: To retrospectively evaluate the efficacy and safety of definitive
      fractionated re-irradiation for local recurrence following stereotactic body
      radiotherapy (SBRT) for primary lung cancer. PATIENTS AND METHODS: Between April
      2003 and December 2011, 398 patients with primary lung tumor underwent SBRT at
      the Kyushu University Hospital, and 46 out of these developed local recurrence
      after SBRT. Definitive fractionated re-irradiation was performed for 17 out of
      the 46 patients. The median dose of re-irradiation was 60 Gy/ 30 fractions.
      Concurrent chemotherapy was given to four patients. RESULTS: The median follow-up
      duration was 12.6 months. At one year post-re-irradiation, local progression-free
      survival was 33.8%; progression-free survival, 30.9%; cause-specific survival,
      79.3%; and overall survival, 74.7%. No severe adverse events were observed during
      the follow-up. CONCLUSION: Definitive fractionated re-irradiation is thought to
      be a safe alternative therapy for local recurrence following SBRT, although its
      efficacy may be not entirely satisfactory.

PMID- 24324113
TI  - A higher body mass index and fat mass are factors predictive of docetaxel dose
      intensity.
AB  - BACKGROUND: Few data are published on docetaxel toxicity in obese patients.
      PATIENTS AND METHODS: All obese patients (n=100) treated for early breast cancer
      during three consecutive years at our Institution, were retrospectively
      investigated. The same number of non-obese patients was randomly selected and
      used as controls. We assessed the factors predictive of the relative dose
      intesity (RDI) reduction, including body composition. RESULTS: A total of 18%
      (n=18) of obese patients and 5% (n=5) of non-obese patients required reduction of
      docetaxel RDI due to toxicity (p=0.008). In a multivariate analysis, body mass
      index (BMI) and age were predictive of a reduction in RDI. Among the 89 patients
      with a determination of body composition, patients with a higher fat mass more
      frequently had a reduction in docetaxel RDI (p=0.002). In multivariate analysis,
      fat mass was the only independent factor predictive of a reduction in docetaxel
      RDI. CONCLUSION: Obese patients treated for early breast cancer more frequently
      required a reduction in docetaxel RDI. Fat mass seems to be the best factor
      predictive of a reduction in docetaxel RDI.

PMID- 24324114
TI  - Dynamic contrast-enhanced magnetic resonance imaging in the early evaluation of
      anti-angiogenic therapy in metastatic renal cell carcinoma.
AB  - AIM: To evaluate the efficacy of dynamic contrast-enhanced magnetic resonance
      (DCE-MR) in the response to anti-angiogenic-targeted agents in patients with
      metastatic renal cell cancer (mRCC). PATIENTS AND METHODS: Twenty-eight
      consecutive patients with sub-diaphragmatic metastases from mRCC were included in
      the protocol after signed informed consent. Baseline characteristics were
      collected and patients were first evaluated with a baseline computed tomography
      (CT) and DCE-MR, subsequently with a new DCE-MRI after 28 days of therapy and
      followed-up with CT until progression. Treatments were administered at standard
      doses. The changes of peak enhancement (DeltaPE) and of the sum of longest tumor
      diameters (DeltaLTD) were related to progression-free survival (PFS) and overall
      survival (OS). RESULTS: The median PFS was 11.4 months [95% Confidence Interval
      (CI): 7.9-14.7 months) and the parametric two-tailed Pearson's test showed a
      positive correlation between the median DeltaPE and the median PFS (rp=0.809;
      p=0.015); no significant correlation was found between the median DeltaLTD and
      the median PFS (rp=-0.446; p=0.27). The median OS was 23.3 months (95% CI: 13.6
      33.0 months) and no significant correlation was found with the median DeltaPE
      (rp=0.218; p=0.60) or with the median DeltaLTD (rp=0.012; p=0.98). CONCLUSION:
      The DeltaPE but not the DeltaLTD was found to be significantly related to PFS;
      these preliminary results suggest extending the number of patients and
      investigating the possible relationship with other tumor characteristics and MRI
      parameters.

PMID- 24324115
TI  - Importance of FOXP3 in prognosis and its relationship with p16 in tonsillar
      squamous cell carcinoma.
AB  - AIM: We examined the relationship between p16, a surrogate marker of human
      papilloma virus (HPV), and FOXP3, marker of regulatory T-cells, in tonsillar
      squamous cell carcinoma (TSCC), and assessed their prognostic potential.
      MATERIALS AND METHODS: The tumors of 79 patients with locally advanced TSCC
      treated from 2000 to 2008 were subjected to immunohistochemistry (IHC) assays for
      p16 and FOXP3 using tissue microarrays. RESULTS: Sixty-three tumors (80%) were
      p16-positive and 38 (48%) were FOXP3-positive on IHC. FOXP3 correlated positively
      with p16 (p=0.011). The p16-positive group had a significantly higher 5-year
      overall survival (OS) rate than the p16-negative group [78% vs. 63%, hazard ratio
      (HR)=0.347, p=0.025]. The FOXP3-positive group had a significantly higher 5-year
      OS rate than the - negative group (89% vs. 61%, HR=0.158, p=0.003). Multivariate
      analysis indicated that FOXP3 is an independent prognostic factor (HR=0.11,
      p=0.001) but p16 did not reach statistical significance (HR=2.17, p=0.131).
      CONCLUSION: FOXP3 expression is associated positively with p16 expression, and is
      a favorable prognostic factor for survival in TSCC.

PMID- 24324116
TI  - Analysis of intrafractional organ motion for patients with prostate cancer using
      soft tissue matching image-guided intensity-modulated radiation therapy by
      helical tomotherapy.
AB  - AIM: To analyze an intrafractional organ motion for patients with prostate cancer
      using soft tissue matching by megavolt computed tomography (MVCT) images during
      the course of image-guided intensity-modulated radiotherapy (IGRT-IMRT) using
      helical tomotherapy. PATIENTS AND METHODS: Data from a total of 10 patients with
      prostate cancer who received IGRT-IMRT were analyzed, and MVCT images were
      acquired before and after radiation therapy. Intra-fractional movement and PTV
      margins for soft tissue matching were calculated by comparing treatment planning
      images with 740 MVCT images for right-left (RL), superior-inferior (SI), and
      anteroposterior (AP) dimensions. A total of 74 Gy/37 fractions were administered.
      A margin to compensate for these variations was calculated using the van Herk's
      equation. RESULTS: The intrafractional motion was 0.03 (-1.3 to 1.4) +/-0.39 mm
      in the RL dimension, 0.08 (-1.8 to 0.28) +/-0.73 mm in the SI dimension, and 0.52
      (-1.8 to 1.8) +/-0.63 mm in the AP dimension. The required PTV margin was 0.60
      mm, 1.10 mm, and 0.78 mm in the RL, SI, and AP dimensions, respectively. Only one
      patient exhibited a deviation greater than 5 mm only once in 37 fractions
      (1/370=0.2%) caused by anal contraction. CONCLUSION: The PTV margin in soft
      tissue matching IGRT-IMRT by helical tomotherapy for a patient with prostate
      cancer was 3 mm or less, and our tentative PTV margin of 3-5 mm is sufficient for
      most patients, if adequate instruction for avoiding anal contraction is given.

PMID- 24324117
TI  - Post-transplantation consolidation and maintenance therapy with lenalidomide for
      Japanese patients with multiple myeloma.
AB  - BACKGROUND: Post-autologous stem cell transplantation (ASCT) consolidation and
      maintenance therapies in multiple myeloma (MM) have recently been the central
      focus of studies. However, there have been no reports of Japanese patients with
      MM treated with post-ASCT consolidation/maintenance therapies. PATIENTS AND
      METHODS: We retrospectively evaluated eight Japanese patients with newly
      diagnosed symptomatic MM who received ASCT after high-dose melphalan, and three
      to four courses of bortezomib-plus-dexamethasone and two courses of lenalidomide
      plus-dexamethasone followed by maintenance lenalidomide for 6-24 months. RESULTS:
      Four patients achieved complete response (CR) after ASCT, and five patients (63%)
      achieved stringent CR after the consolidation and maintenance therapy; two out of
      these five were in molecular CR. At the median follow-up of 38 months, all
      patients were alive and only one patient had disease progression following post
      ASCT therapy. CONCLUSION: Post-ASCT consolidation and maintenance therapy using
      lenalidomide may be effective in the treatment of Japanese patients with MM.

PMID- 24324118
TI  - Re-irradiation using interstitial brachytherapy increases vaginal mucosal
      reaction compared to initial brachytherapy in patients with gynecological cancer.
AB  - AIM: To examine the vaginal mucosal reaction in gynecological cancer patients
      after re-irradiation using interstitial brachytherapy (re-ISBT) compared to
      initial brachytherapy. PATIENTS AND METHODS: A comparison was made between re
      ISBT (n=14) and the initial brachytherapy group consisting of 63 cases of
      intracavitary brachytherapy (ICBT) and 37 of interstitial brachytherapy (ISBT).
      We examined the modified Dishe score at 6, 12, 18, 24, 36, and 60 months after
      treatment with a median follow-up time of 41 months (range: 6-144 months). Re
      ISBT was performed using 42-51 Gy in 7-8 fractions in 2-5 days (twice a day)
      without external irradiation. RESULTS: For bleeding and discharge, fewer than 10%
      of patients exhibited grade 1 reactions and no statistically significantly
      differences were found between re-ISBT and initial brachytherapy. Re-ISBT
      increased erythema (grade 0/1/2=29%/57%/14%) compared with initial brachytherapy
      (grade 0/1/2=64%/31%/5%, p=0.03). Four out of 14 patients had grade 1 ulceration
      or higher after re-ISBT, whereas five patients experienced grade 1 ulceration
      after initial in brachytherapy (p=0.001). Notably, a fistula appeared in one
      patient in the re-ISBT group. There is no difference between re-ISBT and fresh
      brachytherapy with regard to telangiectasia, stenosis and pallor reactions.
      Increased cumulative (previous plus present treatment) equivalent dose in a 2-Gy
      fraction was correlated to a higher grade of erythema and ulceration. CONCLUSION:
      Re-ISBT increased the vaginal mucosal reaction, as shown by increased erythema
      and ulceration, more than initial brachytherapy, with a higher cumulative
      radiation dose, but the reaction was mild in almost all cases.

PMID- 24324119
TI  - Rituximab in the treatment of EBV-positive low grade B-cell lymphoma.
AB  - BACKGROUND: Following infection of B lymphocytes by Epstein Barr virus (EBV), the
      viral genome remains in the nucleus, and a latency phase is established, during
      which only a small proportion of the viral genes are expressed. Among them, LMP1
      is essential for transformation. Rituximab is a potent agent used in the
      treatment of low grade B-cell lymphomas and is also widely used for the treatment
      of post-transplant lymphoproliferative disorders caused by EBV. The effect of
      rituximab treatment on the latent EBV infection in non-transplant patients with
      lymphoproliferative disorders has never been studied to our knowledge. PATIENTS
      AND METHODS: We studied, the effect of rituximab-based immunochemotherapy on the
      EBV status of 44 patients with leukemic low grade B-cell lymphoma. RESULTS: After
      three cycles of rituximab-based treatment, only 1/17 patients was still positive
      for EBV. DISCUSSION: Our results suggest that rituximab used in the treatment of
      EBV-positive low-grade lymphoma is efficient in eradicating the virus from the
      peripheral blood, a fact with potential implications in the course and prognosis
      of the disease.

PMID- 24324120
TI  - Phase I pharmacokinetic study of S-1 granules and nedaplatin for advanced head
      and neck cancer.
AB  - AIM: We performed a pharmacokinetic phase I trial of the combination of S-1
      granules and nedaplatin for head and neck squamous cell carcinoma (HNSCC).
      PATIENTS AND METHODS: Patients were treated with both nedaplatin on day 1 at a
      dose starting at 80 mg/m(2) (level 1) escalating up to 90 mg/m(2) (level 2), and
      S-1 granules at a daily dose of 80 mg/m(2) on days 1 to 14 every three weeks. The
      primary end-point was determination of the recommended dose. RESULTS: Twenty
      patients were enrolled. Dose-limiting toxicities occurred in one out of six
      patients at dose level 1 (neutropenia) and in all three patients at level 2
      (neutropenia and thrombocytopenia). The recommended dose was determined as level
      1. Pharmacokinetic parameters of S-1 granule did not differ from the capsula
      formulation. The response rate was 42.1%. CONCLUSION: This combination was well
      tolerated and manifested a promising activity against HNSCC.

PMID- 24324133
TI  - Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling
      in breast cancer cells.
AB  - Overexpression of Rho kinase 1 (ROCK1) and the G protein RhoA is implicated in
      breast cancer progression, but oncogenic mutations are rare, and the molecular
      mechanisms that underlie increased ROCK1 and RhoA expression have not been
      determined. RhoA-bound ROCK1 phosphorylates myosin light chain (MLC), which is
      required for actin-myosin contractility. RhoA also activates focal adhesion
      kinase (FAK) signaling. Together, these pathways are critical determinants of the
      motile and invasive phenotype of cancer cells. We report that hypoxia-inducible
      factors coordinately activate RhoA and ROCK1 expression and signaling in breast
      cancer cells, leading to cell and matrix contraction, focal adhesion formation,
      and motility through phosphorylation of MLC and FAK. Thus, intratumoral hypoxia
      acts as an oncogenic stimulus by triggering hypoxia-inducible factor -> RhoA ->
      ROCK1 -> MLC -> FAK signaling in breast cancer cells. 

PMID- 24324134
TI  - 1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS
      localization.
AB  - Pharmacologic targeting of T helper (TH) cell trafficking poses an attractive
      opportunity for amelioration of autoimmune diseases such as multiple sclerosis
      (MS). MS risk is associated with vitamin D deficiency, and its bioactive form,
      1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to prevent experimental
      autoimmune encephalomyelitis, a mouse model of MS, via an incompletely understood
      mechanism. Herein, we systematically examined 1,25(OH)2D3 effects on TH cells
      during their migration from the lymph nodes to the CNS. Our data demonstrate that
      myelin-reactive TH cells are successfully generated in the presence of
      1,25(OH)2D3, secrete proinflammatory cytokines, and do not preferentially
      differentiate into suppressor T cells. These cells are able to leave the lymph
      node, enter the peripheral circulation, and migrate to the s.c. immunization
      sites. However, TH cells from 1,25(OH)2D3-treated mice are unable to enter the
      CNS parenchyma but are instead maintained in the periphery. Upon treatment
      cessation, mice rapidly develop experimental autoimmune encephalomyelitis,
      demonstrating that 1,25(OH)2D3 prevents the disease only temporarily likely by
      halting TH cell migration into the CNS. 

PMID- 24324135
TI  - Structural basis for 2'-phosphate incorporation into glycogen by glycogen
      synthase.
AB  - Glycogen is a glucose polymer that contains minor amounts of covalently attached
      phosphate. Hyperphosphorylation is deleterious to glycogen structure and can lead
      to Lafora disease. Recently, it was demonstrated that glycogen synthase catalyzes
      glucose-phosphate transfer in addition to its characteristic glucose transfer
      reaction. Glucose-1,2-cyclic-phosphate (GCP) was proposed to be formed from UDP
      Glc breakdown and subsequently transferred, thus providing a source of phosphate
      found in glycogen. To gain further insight into the molecular basis for glucose
      phosphate transfer, two structures of yeast glycogen synthase were determined; a
      3.0-A resolution structure of the complex with UMP/GCP and a 2.8-A resolution
      structure of the complex with UDP/glucose. Structural superposition of the
      complexes revealed that the bound ligands and most active site residues are
      positioned similarly, consistent with the use of a common transfer mechanism for
      both reactions. The N-terminal domain of the UDP-glucose complex was found to be
      13.3 degrees  more closed compared with a UDP complex. However, the UMP . GCP
      complex was 4.8 degrees  less closed than the glucose complex, which may explain
      the low efficiency of GCP transfer. Modeling of either alpha- or beta-glucose or
      a mixture of both anomers can account for the observed electron density of the
      UDP-glucose complex. NMR studies of UDP-Glc hydrolysis by yeast glycogen synthase
      were used to verify the stereochemistry of the product, and they also showed
      synchronous GCP accumulation. The similarities in the active sites of glycogen
      synthase and glycogen phosphorylase support the idea of a common catalytic
      mechanism in GT-B enzymes independent of the specific reaction catalyzed.

PMID- 24324136
TI  - Structural basis of reverse nucleotide polymerization.
AB  - Nucleotide polymerization proceeds in the forward (5'-3') direction. This tenet
      of the central dogma of molecular biology is found in diverse processes including
      transcription, reverse transcription, DNA replication, and even in lagging strand
      synthesis where reverse polymerization (3'-5') would present a "simpler"
      solution. Interestingly, reverse (3'-5') nucleotide addition is catalyzed by the
      tRNA maturation enzyme tRNA(His) guanylyltransferase, a structural homolog of
      canonical forward polymerases. We present a Candida albicans tRNA(His)
      guanylyltransferase-tRNA(His) complex structure that reveals the structural basis
      of reverse polymerization. The directionality of nucleotide polymerization is
      determined by the orientation of approach of the nucleotide substrate. The tRNA
      substrate enters the enzyme's active site from the opposite direction (180
      degrees  flip) compared with similar nucleotide substrates of canonical 5'-3'
      polymerases, and the finger domains are on opposing sides of the core palm
      domain. Structural, biochemical, and phylogenetic data indicate that reverse
      polymerization appeared early in evolution and resembles a mirror image of the
      forward process. 

PMID- 24324137
TI  - Structure of the ribosome with elongation factor G trapped in the
      pretranslocation state.
AB  - During protein synthesis, tRNAs and their associated mRNA codons move
      sequentially on the ribosome from the A (aminoacyl) site to the P (peptidyl) site
      to the E (exit) site in a process catalyzed by a universally conserved ribosome
      dependent GTPase [elongation factor G (EF-G) in prokaryotes and elongation factor
      2 (EF-2) in eukaryotes]. Although the high-resolution structure of EF-G bound to
      the posttranslocation ribosome has been determined, the pretranslocation
      conformation of the ribosome bound with EF-G and A-site tRNA has evaded
      visualization owing to the transient nature of this state. Here we use electron
      cryomicroscopy to determine the structure of the 70S ribosome with EF-G, which is
      trapped in the pretranslocation state using antibiotic viomycin. Comparison with
      the posttranslocation ribosome shows that the small subunit of the
      pretranslocation ribosome is rotated by ~12 degrees  relative to the large
      subunit. Domain IV of EF-G is positioned in the cleft between the body and head
      of the small subunit outwardly of the A site and contacts the A-site tRNA. Our
      findings suggest a model in which domain IV of EF-G promotes the translocation of
      tRNA from the A to the P site as the small ribosome subunit spontaneously rotates
      back from the hybrid, rotated state into the nonrotated posttranslocation state. 

PMID- 24324138
TI  - Mechanosensory responses of osteocytes to physiological forces occur along
      processes and not cell body and require alphaVbeta3 integrin.
AB  - Osteocytes in the lacunar-canalicular system of the bone are thought to be the
      cells that sense mechanical loading and transduce mechanical strain into
      biomechanical responses. The goal of this study was to evaluate the extent to
      which focal mechanical stimulation of osteocyte cell body and process led to
      activation of the cells, and determine whether integrin attachments play a role
      in osteocyte activation. We use a novel Stokesian fluid stimulus probe to
      hydrodynamically load osteocyte processes vs. cell bodies in murine long bone
      osteocyte Y4 (MLO-Y4) cells with physiological-level forces <10 pN without probe
      contact, and measured intracellular Ca(2+) responses. Our results indicate that
      osteocyte processes are extremely responsive to piconewton-level mechanical
      loading, whereas the osteocyte cell body and processes with no local attachment
      sites are not. Ca(2+) signals generated at stimulated sites spread within the
      processes with average velocity of 5.6 MUm/s. Using the near-infrared
      fluorescence probe IntegriSense 750, we demonstrated that inhibition of
      alphaVbeta3 integrin attachment sites compromises the response to probe
      stimulation. Moreover, using apyrase, an extracellular ATP scavenger, we showed
      that Ca(2+) signaling from the osteocyte process to the cell body was greatly
      diminished, and thus dependent on ATP-mediated autocrine signaling. These
      findings are consistent with the hypothesis that osteocytes in situ are highly
      polarized cells, where mechanotransduction occurs at substrate attachment sites
      along the processes at force levels predicted to occur at integrin attachment
      sites in vivo. We also demonstrate the essential role of alphaVbeta3 integrin in
      osteocyte-polarized mechanosensing and mechanotransduction. 

PMID- 24324139
TI  - HPr antagonizes the anti-sigma70 activity of Rsd in Escherichia coli.
AB  - The bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) is a
      multicomponent system that participates in a variety of physiological processes
      in addition to the phosphorylation-coupled transport of numerous sugars. In
      Escherichia coli and other enteric bacteria, enzyme IIA(Glc) (EIIA(Glc)) is known
      as the central processing unit of carbon metabolism and plays multiple roles,
      including regulation of adenylyl cyclase, the fermentation/respiration switch
      protein FrsA, glycerol kinase, and several non-PTS transporters, whereas the only
      known regulatory role of the E. coli histidine-containing phosphocarrier protein
      HPr is in the activation of glycogen phosphorylase. Because HPr is known to be
      more abundant than EIIA(Glc) in enteric bacteria, we assumed that there might be
      more regulatory mechanisms connected with HPr. The ligand fishing experiment in
      this study identified Rsd, an anti-sigma factor known to complex with sigma(70)
      in stationary-phase cells, as an HPr-binding protein in E. coli. Only the
      dephosphorylated form of HPr formed a tight complex with Rsd and thereby
      inhibited complex formation between Rsd and sigma(70). Dephosphorylated HPr, but
      not phosphorylated HPr, antagonized the inhibitory effect of Rsd on sigma(70)
      dependent transcriptions both in vivo and in vitro, and also influenced the
      competition between sigma(70) and sigma(S) for core RNA polymerase in the
      presence of Rsd. Based on these data, we propose that the anti-sigma(70) activity
      of Rsd is regulated by the phosphorylation state-dependent interaction of HPr
      with Rsd. 

PMID- 24324140
TI  - Resolution doubling in fluorescence microscopy with confocal spinning-disk image
      scanning microscopy.
AB  - We demonstrate how a conventional confocal spinning-disk (CSD) microscope can be
      converted into a doubly resolving image scanning microscopy (ISM) system without
      changing any part of its optical or mechanical elements. Making use of the
      intrinsic properties of a CSD microscope, we illuminate stroboscopically,
      generating an array of excitation foci that are moved across the sample by
      varying the phase between stroboscopic excitation and rotation of the spinning
      disk. ISM then generates an image with nearly doubled resolution. Using
      conventional fluorophores, we have imaged single nuclear pore complexes in the
      nuclear membrane and aggregates of GFP-conjugated Tau protein in three
      dimensions. Multicolor ISM was shown on cytoskeletal-associated structural
      proteins and on 3D four-color images including MitoTracker and Hoechst staining.
      The simple adaptation of conventional CSD equipment allows superresolution
      investigations of a broad variety of cell biological questions. 

PMID- 24324141
TI  - Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and
      periodontal bone loss.
AB  - The purpose of this study was to elucidate the role of nucleotide binding
      oligomerization domain-containing protein 2 (NOD2) signaling in atherosclerosis
      and periodontal bone loss using an Apolipoprotein E(-/-) (ApoE(-/-)) mouse model
      based on the proposed role of NOD2 in inflammation. NOD2(-/-)ApoE(-/-) and ApoE(
      /-) mice fed a standard chow diet were given an oral gavage of Porphyromonas
      gingivalis for 15 wk. NOD2(-/-)ApoE(-/-) mice exhibited significant increases in
      inflammatory cytokines, alveolar bone loss, cholesterol, and atherosclerotic
      lesions in the aorta and the heart compared with ApoE(-/-) mice. In contrast,
      ApoE(-/-) mice injected i.p. with Muramyl DiPeptide (MDP) to stimulate NOD2 and
      given an oral gavage of P. gingivalis displayed a reduction of serum inflammatory
      cytokines, alveolar bone loss, cholesterol, and atherosclerotic lesions in the
      aorta and aortic sinus compared with ApoE(-/-) mice orally challenged but
      injected with saline. A reduction in body weight gain was observed in ApoE(-/-)
      mice fed a high-fat diet (HFD) and injected with MDP compared with ApoE(-/-) mice
      fed a high-fat diet but injected with saline. MDP treatment of bone marrow
      derived macrophages incubated with P. gingivalis increased mRNA expressions of
      NOD2, Toll-like receptor 2, myeloid differentiation primary response gene 88, and
      receptor-interacting protein-2 but reduced the expressions of inhibitor of NF
      kappaB kinase-beta, NF-kappaB, c-Jun N-terminal kinase 3, and TNF-alpha protein
      levels compared with saline control, highlighting pathways involved in MDP
      antiinflammatory effects. MDP activation of NOD2 should be considered in the
      treatment of inflammatory processes affecting atherosclerosis, periodontal bone
      loss ,and possibly, diet-induced weight gain. 

PMID- 24324142
TI  - TGF-beta directs trafficking of the epithelial sodium channel ENaC which has
      implications for ion and fluid transport in acute lung injury.
AB  - TGF-beta is a pathogenic factor in patients with acute respiratory distress
      syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-beta
      pathway is described, which rapidly promoted internalization of the
      alphabetagamma epithelial sodium channel (ENaC) complex from the alveolar
      epithelial cell surface, leading to persistence of pulmonary edema. TGF-beta
      applied to the alveolar airspaces of live rabbits or isolated rabbit lungs
      blocked sodium transport and caused fluid retention, which--together with patch
      clamp and flow cytometry studies--identified ENaC as the target of TGF-beta. TGF
      beta rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4
      phosphate 5-kinase 1alpha, and NADPH oxidase 4 (NOX4) to produce reactive oxygen
      species, driving internalization of betaENaC, the subunit responsible for cell
      surface stability of the alphabetagammaENaC complex. ENaC internalization was
      dependent on oxidation of betaENaC Cys(43). Treatment of alveolar epithelial
      cells with bronchoalveolar lavage fluids from ARDS patients drove betaENaC
      internalization, which was inhibited by a TGF-beta neutralizing antibody and a
      Tgfbr1 inhibitor. Pharmacological inhibition of TGF-beta signaling in vivo in
      mice, and genetic ablation of the nox4 gene in mice, protected against perturbed
      lung fluid balance in a bleomycin model of lung injury, highlighting a role for
      both proximal and distal components of this unique ENaC regulatory pathway in
      lung fluid balance. These data describe a unique TGF-beta-dependent mechanism
      that regulates ion and fluid transport in the lung, which is not only relevant to
      the pathological mechanisms of ARDS, but might also represent a physiological
      means of acutely regulating ENaC activity in the lung and other organs.

PMID- 24324143
TI  - Cultural assemblages show nested structure in humans and chimpanzees but not
      orangutans.
AB  - The evolution of hominin culture is well-documented in the archeological and
      fossil record, but such a record is largely absent for nonhuman primates. An
      alternative approach to studying cultural evolution is to examine patterns of
      modern cultural variation. In this article we measure nestedness across human and
      great ape "cultural repertoires" to gain insight into the accumulation and
      maintenance of putative cultural diversity in these species. Cultural assemblages
      are nested if cultures with a small repertoire of traits tend to comprise a
      proper subset of those traits present in more complex cultures. This nesting will
      occur if some traits are sequentially gained or lost, which may be because of the
      differential dispersal or extinction of traits. Here we apply statistical tools
      from ecology to examine the degree of nestedness in four datasets documenting the
      presence or absence of specific cultural traits across indigenous human
      populations in North America and New Guinea. We then compare the human data to
      patterns observed for putative cultural traits in chimpanzee and orangutan
      populations. In both humans and chimpanzees, cultural diversity is highly
      nonrandom, showing significant nested structure for all of the datasets examined.
      We find no evidence for nestedness in the orangutan cultural data. These findings
      are consistent with a sequential "layering" of cultural diversity in humans and
      chimpanzees, but not orangutans. Such an interpretation implies that the traits
      required for sequential cultural evolution first appeared in the last common
      ancestor of chimpanzees and humans. 

PMID- 24324145
TI  - Long-term effect of September 11 on the political behavior of victims' families
      and neighbors.
AB  - This article investigates the long-term effect of September 11, 2001 on the
      political behaviors of victims' families and neighbors. Relative to comparable
      individuals, family members and residential neighbors of victims have become--and
      have stayed--significantly more active in politics in the last 12 years, and they
      have become more Republican on account of the terrorist attacks. The method used
      to demonstrate these findings leverages the random nature of the terrorist attack
      to estimate a causal effect and exploits new techniques to link multiple,
      individual-level, governmental databases to measure behavioral change without
      relying on surveys or aggregate analysis.

PMID- 24324144
TI  - Critical slowing down as early warning for the onset and termination of
      depression.
AB  - About 17% of humanity goes through an episode of major depression at some point
      in their lifetime. Despite the enormous societal costs of this incapacitating
      disorder, it is largely unknown how the likelihood of falling into a depressive
      episode can be assessed. Here, we show for a large group of healthy individuals
      and patients that the probability of an upcoming shift between a depressed and a
      normal state is related to elevated temporal autocorrelation, variance, and
      correlation between emotions in fluctuations of autorecorded emotions. These are
      indicators of the general phenomenon of critical slowing down, which is expected
      to occur when a system approaches a tipping point. Our results support the
      hypothesis that mood may have alternative stable states separated by tipping
      points, and suggest an approach for assessing the likelihood of transitions into
      and out of depression. 

PMID- 24324146
TI  - RNF168 ubiquitylates 53BP1 and controls its response to DNA double-strand breaks.
AB  - Defective signaling or repair of DNA double-strand breaks has been associated
      with developmental defects and human diseases. The E3 ligase RING finger 168
      (RNF168), mutated in the human radiosensitivity, immunodeficiency, dysmorphic
      features, and learning difficulties syndrome, was shown to ubiquitylate H2A-type
      histones, and this ubiquitylation was proposed to facilitate the recruitment of
      p53-binding protein 1 (53BP1) to the sites of DNA double-strand breaks. In
      contrast to more upstream proteins signaling DNA double-strand breaks (e.g.,
      RNF8), deficiency of RNF168 fully prevents both the initial recruitment to and
      retention of 53BP1 at sites of DNA damage; however, the mechanism for this
      difference has remained unclear. Here, we identify mechanisms that regulate 53BP1
      recruitment to the sites of DNA double-strand breaks and provide evidence that
      RNF168 plays a central role in the regulation of 53BP1 functions. RNF168 mediates
      K63-linked ubiquitylation of 53BP1 which is required for the initial recruitment
      of 53BP1 to sites of DNA double-strand breaks and for its function in DNA damage
      repair, checkpoint activation, and genomic integrity. Our findings highlight the
      multistep roles of RNF168 in signaling DNA damage. 

PMID- 24324147
TI  - A theory for how sensorimotor skills are learned and retained in noisy and
      nonstationary neural circuits.
AB  - During the process of skill learning, synaptic connections in our brains are
      modified to form motor memories of learned sensorimotor acts. The more plastic
      the adult brain is, the easier it is to learn new skills or adapt to neurological
      injury. However, if the brain is too plastic and the pattern of synaptic
      connectivity is constantly changing, new memories will overwrite old memories,
      and learning becomes unstable. This trade-off is known as the stability
      plasticity dilemma. Here a theory of sensorimotor learning and memory is
      developed whereby synaptic strengths are perpetually fluctuating without causing
      instability in motor memory recall, as long as the underlying neural networks are
      sufficiently noisy and massively redundant. The theory implies two distinct
      stages of learning--preasymptotic and postasymptotic--because once the error
      drops to a level comparable to that of the noise-induced error, further error
      reduction requires altered network dynamics. A key behavioral prediction derived
      from this analysis is tested in a visuomotor adaptation experiment, and the
      resultant learning curves are modeled with a nonstationary neural network. Next,
      the theory is used to model two-photon microscopy data that show, in animals,
      high rates of dendritic spine turnover, even in the absence of overt behavioral
      learning. Finally, the theory predicts enhanced task selectivity in the responses
      of individual motor cortical neurons as the level of task expertise increases.
      From these considerations, a unique interpretation of sensorimotor memory is
      proposed--memories are defined not by fixed patterns of synaptic weights but,
      rather, by nonstationary synaptic patterns that fluctuate coherently.

PMID- 24324148
TI  - Biased migration of confined neutrophil-like cells in asymmetric hydraulic
      environments.
AB  - Cells integrate multiple measurement modalities to navigate their environment.
      Soluble and substrate-bound chemical gradients and physical cues have all been
      shown to influence cell orientation and migration. Here we investigate the role
      of asymmetric hydraulic pressure in directional sensing. Cells confined in
      microchannels identified and chose a path of lower hydraulic resistance in the
      absence of chemical cues. In a bifurcating channel with asymmetric hydraulic
      resistances, this choice was preceded by the elaboration of two leading edges
      with a faster extension rate along the lower resistance channel. Retraction of
      the "losing" edge appeared to precipitate a final choice of direction. The
      pressure differences altering leading edge protrusion rates were small,
      suggesting weak force generation by leading edges. The response to the physical
      asymmetry was able to override a dynamically generated chemical cue. Motile cells
      may use this bias as a result of hydraulic resistance, or "barotaxis," in concert
      with chemotaxis to navigate complex environments. 

PMID- 24324149
TI  - Necking and failure of constrained 3D microtissues induced by cellular tension.
AB  - In this paper we report a fundamental morphological instability of constrained 3D
      microtissues induced by positive chemomechanical feedback between actomyosin
      driven contraction and the mechanical stresses arising from the constraints.
      Using a 3D model for mechanotransduction we find that perturbations in the shape
      of contractile tissues grow in an unstable manner leading to formation of "necks"
      that lead to the failure of the tissue by narrowing and subsequent elongation.
      The magnitude of the instability is shown to be determined by the level of active
      contractile strain, the stiffness of the extracellular matrix, and the components
      of the tissue that act in parallel with the active component and the stiffness of
      the boundaries that constrain the tissue. A phase diagram that demarcates stable
      and unstable behavior of 3D tissues as a function of these material parameters is
      derived. The predictions of our model are verified by analyzing the necking and
      failure of normal human fibroblast tissue constrained in a loop-ended dog-bone
      geometry and cardiac microtissues constrained between microcantilevers. By
      analyzing the time evolution of the morphology of the constrained tissues we have
      quantitatively determined the chemomechanical coupling parameters that
      characterize the generation of active stresses in these tissues. More generally,
      the analytical and numerical methods we have developed provide a quantitative
      framework to study how contractility can influence tissue morphology in complex
      3D environments such as morphogenesis and organogenesis. 

PMID- 24324150
TI  - Antagonism of SAMHD1 is actively maintained in natural infections of simian
      immunodeficiency virus.
AB  - Restriction factors are effectors of the innate immune response to viral
      pathogens that inhibit viral replication by operating as molecular barriers to
      steps of the viral life cycle. The restriction factor SAMHD1 blocks lentiviral
      reverse transcription in myeloid cells and resting CD4+ T cells. Many lineages of
      lentiviruses, including HIV-2 and other simian immunodeficiency viruses, encode
      accessory genes that serve to counteract host SAMHD1 restriction by causing
      degradation of the antiviral factor. The viral accessory protein Vpr is
      responsible for SAMHD1 degradation in some lineages of lentiviruses, whereas in
      others the related protein Vpx assumes this task. However, HIV-1 has no SAMHD1
      degradation capability, leading to questions about the selective advantage of
      this activity. We use an evolutionary approach to examine the importance of
      SAMHD1 antagonism for viral fitness by studying adaptation to host SAMHD1 in
      natural simian immunodeficiency virus infections of African Green Monkeys. We
      identified multiple SAMHD1 haplotypes in African Green Monkeys and find that the
      vpr gene from different strains of Simian Immunodeficiency Virus has adapted to
      the polymorphisms of the African Green Monkey population in which it is found.
      Such evidence of viral adaptation to host restriction indicates that SAMHD1
      antagonism is actively maintained in natural infections and that this function
      must be advantageous to viral fitness, despite its absence in HIV-1. 

PMID- 24324151
TI  - Phenalenone-type phytoalexins mediate resistance of banana plants (Musa spp.) to
      the burrowing nematode Radopholus similis.
AB  - The global yield of bananas-one of the most important food crops-is severely
      hampered by parasites, such as nematodes, which cause yield losses up to 75%.
      Plant-nematode interactions of two banana cultivars differing in susceptibility
      to Radopholus similis were investigated by combining the conventional and
      spatially resolved analytical techniques (1)H NMR spectroscopy, matrix-free UV
      laser desorption/ionization mass spectrometric imaging, and Raman
      microspectroscopy. This innovative combination of analytical techniques was
      applied to isolate, identify, and locate the banana-specific type of
      phytoalexins, phenylphenalenones, in the R. similis-caused lesions of the plants.
      The striking antinematode activity of the phenylphenalenone anigorufone, its
      ingestion by the nematode, and its subsequent localization in lipid droplets
      within the nematode is reported. The importance of varying local concentrations
      of these specialized metabolites in infected plant tissues, their involvement in
      the plant's defense system, and derived strategies for improving banana
      resistance are highlighted. 

PMID- 24324152
TI  - The adjuvant MF59 induces ATP release from muscle that potentiates response to
      vaccination.
AB  - Vaccines are the most effective agents to control infections. In addition to the
      pathogen antigens, vaccines contain adjuvants that are used to enhance protective
      immune responses. However, the molecular mechanism of action of most adjuvants is
      ill-known, and a better understanding of adjuvanticity is needed to develop
      improved adjuvants based on molecular targets that further enhance vaccine
      efficacy. This is particularly important for tuberculosis, malaria, AIDS, and
      other diseases for which protective vaccines do not exist. Release of endogenous
      danger signals has been linked to adjuvanticity; however, the role of
      extracellular ATP during vaccination has never been explored. Here, we tested
      whether ATP release is involved in the immune boosting effect of four common
      adjuvants: aluminum hydroxide, calcium phosphate, incomplete Freund's adjuvant,
      and the oil-in-water emulsion MF59. We found that intramuscular injection is
      always associated with a weak transient release of ATP, which was greatly
      enhanced by the presence of MF59 but not by all other adjuvants tested. Local
      injection of apyrase, an ATP-hydrolyzing enzyme, inhibited cell recruitment in
      the muscle induced by MF59 but not by alum or incomplete Freund's adjuvant. In
      addition, apyrase strongly inhibited influenza-specific T-cell responses and
      hemagglutination inhibition titers in response to an MF59-adjuvanted trivalent
      influenza vaccine. These data demonstrate that a transient ATP release is
      required for innate and adaptive immune responses induced by MF59 and link
      extracellular ATP with an enhanced response to vaccination. 

PMID- 24324153
TI  - Evolutionary genomics of epidemic and nonepidemic strains of Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen of humans and is a major
      cause of morbidity and mortality in patients with cystic fibrosis (CF). Prolonged
      infection of the respiratory tract can lead to adaptation of the pathogen to the
      CF lung environment. To examine the general patterns of adaptation associated
      with chronic infection, we obtained genome sequences from a collection of P.
      aeruginosa isolated from airways of patients with CF. Our analyses support a
      nonclonal epidemic population structure, with a background of unique, recombining
      genotypes, and the rare occurrence of successful epidemic clones. We present
      unique genome sequence evidence for the intercontinental spread of an epidemic
      strain shared between CF clinics in the United Kingdom and North America.
      Analyses of core and accessory genomes identified candidate genes and important
      functional pathways associated with adaptive evolution. Many genes of interest
      were involved in biological functions with obvious roles in this pathosystem,
      such as biofilm formation, antibiotic metabolism, pathogenesis, transport,
      reduction/oxidation, and secretion. Key factors driving the adaptive evolution of
      this pathogen within the host appear to be the presence of oxidative stressors
      and antibiotics. Regions of the accessory genome unique to the epidemic strain
      were enriched for genes in transporter families that efflux heavy metals and
      antibiotics. The epidemic strain was significantly more resistant than
      nonepidemic strains to three different antibiotics. Multiple lines of evidence
      suggest that selection imposed by the CF lung environment has a major influence
      on genomic evolution and the genetic characteristics of P. aeruginosa isolates
      causing contemporary infection. 

PMID- 24324154
TI  - Disease diversity and FLT3 mutations.

PMID- 24324155
TI  - Restoration of function after brain damage using a neural prosthesis.
AB  - Neural interface systems are becoming increasingly more feasible for brain repair
      strategies. This paper tests the hypothesis that recovery after brain injury can
      be facilitated by a neural prosthesis serving as a communication link between
      distant locations in the cerebral cortex. The primary motor area in the cerebral
      cortex was injured in a rat model of focal brain injury, disrupting communication
      between motor and somatosensory areas and resulting in impaired reaching and
      grasping abilities. After implantation of microelectrodes in cerebral cortex, a
      neural prosthesis discriminated action potentials (spikes) in premotor cortex
      that triggered electrical stimulation in somatosensory cortex continuously over
      subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats
      showed substantially improved reaching and grasping functions that were
      indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes
      evoked by the stimulation provides compelling evidence that the neural prosthesis
      enhanced functional connectivity between the two target areas. This proof-of
      concept study demonstrates that neural interface systems can be used effectively
      to bridge damaged neural pathways functionally and promote recovery after brain
      injury. 

PMID- 24324156
TI  - Genetic mapping of adaptation reveals fitness tradeoffs in Arabidopsis thaliana.
AB  - Organisms inhabiting different environments are often locally adapted, and yet
      despite a considerable body of theory, the genetic basis of local adaptation is
      poorly understood. Unanswered questions include the number and effect sizes of
      adaptive loci, whether locally favored loci reduce fitness elsewhere (i.e.,
      fitness tradeoffs), and whether a lack of genetic variation limits adaptation. To
      address these questions, we mapped quantitative trait loci (QTL) for total
      fitness in 398 recombinant inbred lines derived from a cross between locally
      adapted populations of the highly selfing plant Arabidopsis thaliana from Sweden
      and Italy and grown for 3 consecutive years at the parental sites (>40,000 plants
      monitored). We show that local adaptation is controlled by relatively few genomic
      regions of small to modest effect. A third of the 15 fitness QTL we detected
      showed evidence of tradeoffs, which contrasts with the minimal evidence for
      fitness tradeoffs found in previous studies. This difference may reflect the
      power of our multiyear study to distinguish conditionally neutral QTL from those
      that reflect fitness tradeoffs. In Sweden, but not in Italy, the local genotype
      underlying fitness QTL was often maladaptive, suggesting that adaptation there is
      constrained by a lack of adaptive genetic variation, attributable perhaps to
      genetic bottlenecks during postglacial colonization of Scandinavia or to recent
      changes in selection regime caused by climate change. Our results suggest that
      adaptation to markedly different environments can be achieved through changes in
      relatively few genomic regions, that fitness tradeoffs are common, and that lack
      of genetic variation can limit adaptation. 

PMID- 24324157
TI  - Visualization of repetitive DNA sequences in human chromosomes with transcription
      activator-like effectors.
AB  - We describe a transcription activator-like effector (TALE)-based strategy, termed
      "TALEColor," for labeling specific repetitive DNA sequences in human chromosomes.
      We designed TALEs for the human telomeric repeat and fused them with any of
      numerous fluorescent proteins (FPs). Expression of these TALE-telomere-FP fusion
      proteins in human osteosarcoma's (U2OS) cells resulted in bright signals
      coincident with telomeres. We also designed TALEs for centromeric sequences
      unique to certain chromosomes, enabling us to localize specific human chromosomes
      in live cells. Meanwhile we generated TALE-FPs in vitro and used them as probes
      to detect telomeres in fixed cells. Using human cells with different average
      telomere lengths, we found that the TALEColor signals correlated positively with
      telomere length. In addition, suspension cells were followed by imaging flow
      cytometry to resolve cell populations with differing telomere lengths. These
      methods may have significant potential both for basic chromosome and genome
      research as well as in clinical applications. 

PMID- 24324158
TI  - TRAF3 enforces the requirement for T cell cross-talk in thymic medullary
      epithelial development.
AB  - Induction of self-tolerance in developing T cells depends on medullary thymic
      epithelial cells (mTECs), whose development, in turn, requires signals from
      single-positive (SP) thymocytes. Thus, the absence of SP thymocytes in Tcra(-/-)
      mice results in a profound deficiency in mTECs. Here, we have probed the
      mechanism that underlies this requirement for cross-talk with thymocytes in
      medullary development. Previous studies have implicated nonclassical NF-kappaB as
      a pathway important in the development of mTECs, because mice lacking RelB, NIK,
      or IKKalpha, critical components of this pathway, have an almost complete absence
      of mTECs, with resulting autoimmune pathology. We therefore assessed the effect
      of selective deletion in TEC of TNF receptor-associated factor 3 (TRAF3), an
      inhibitor of nonclassical NF-kappaB signaling. Deletion of TRAF3 in thymic
      epithelial cells allowed RelB-dependent development of normal numbers of AIRE
      expressing mTECs in the complete absence of SP thymocytes. Thus, mTEC development
      can occur in the absence of cross-talk with SP thymocytes, and signals provided
      by SP T cells are needed to overcome TRAF3-imposed arrest in mTEC development
      mediated by inhibition of nonclassical NF-kappaB. We further observed that TRAF3
      deletion is also capable of overcoming all requirements for LTbetaR and CD40,
      which are otherwise necessary for mTEC development, but is not sufficient to
      overcome the requirement for RANKL, indicating a role for RANKL that is distinct
      from the signals provided by SP thymocytes. We conclude that TRAF3 plays a
      central role in regulation of mTEC development by imposing requirements for SP T
      cells and costimulation-mediated cross-talk in generation of the medullary
      compartment. 

PMID- 24324159
TI  - Genetic disruption of CD8+ Treg activity enhances the immune response to viral
      infection.
AB  - The immunological interactions that regulate the T-cell response to chronic viral
      infection are insufficiently understood. Here we study a cellular interaction
      that may enhance the antiviral immune response and constrain immunopathology. We
      analyze the contribution of Qa-1-restricted CD8(+) regulatory T cells (Treg
      cells) to antiviral immunity after infection by lymphocytic choriomeningitis
      virus. These CD8(+) Treg cells recognize and eliminate target cells through an
      interaction with the murine class Ib MHC molecule Qa-1 (HLA-E in humans). Using
      Qa-1 mutant mice (B6.Qa-1-D227K [B6-DK]) that harbor a single mutation that
      abrogates binding of Qa-1 peptide to the CD8-TCR (T-cell receptor) complex, we
      show that disruption of immune suppression mediated by CD8(+) Treg cells results
      in robust antiviral immune responses in both acute and chronic viral infection.
      Enhanced antiviral responses of B6-DK mice were accompanied by increased control
      of virus, reduced tissue inflammation in the acute phase, and dramatic
      alleviation of disease in the chronic phase. In addition, CD8(+) effector T cells
      in B6-DK mice displayed a less exhausted phenotype characterized by decreased
      expression of programmed cell death 1 (PD-1), LAG3 (CD223), and 2B4 (CD244) and
      increased expression of NKG2D (CD314) and killer cell lectin-like receptor
      subfamily G member 1 (KLRG1). Enhanced antiviral immunity in B6-DK mice
      reflected, in part, reduced inhibition of CD8(+) effector cells by CD8(+) Treg
      cells. These findings indicate that direct inhibition of effector CD8(+) T cells
      by Qa-1-restricted CD8(+) Treg cells results in increased disease severity and
      delayed recovery. These data suggest that depletion or inactivation of CD8(+)
      Treg cells represents a potentially effective strategy to enhance protective
      immunity to chronic viral infection. 

PMID- 24324160
TI  - Transition state and ground state properties of the helix-coil transition in
      peptides deduced from high-pressure studies.
AB  - Volume changes associated with protein folding reactions contain valuable
      information about the folding mechanism and the nature of the transition state.
      However, meaningful interpretation of such data requires that overall volume
      changes be deconvoluted into individual contributions from different structural
      components. Here we focus on one type of structural element, the alpha-helix, and
      measure triplet-triplet energy transfer at high pressure to determine volume
      changes associated with the helix-coil transition. Our results reveal that the
      volume of a 21-amino-acid alanine-based peptide shrinks upon helix formation.
      Thus, helices, in contrast with native proteins, become more stable with
      increasing pressure, explaining the frequently observed helical structures in
      pressure-unfolded proteins. Both helix folding and unfolding become slower with
      increasing pressure. The volume changes associated with the addition of a single
      helical residue to a preexisting helix were obtained by comparing the
      experimental results with Monte Carlo simulations based on a kinetic linear Ising
      model. The reaction volume for adding a single residue to a helix is small and
      negative (-0.23 cm(3) per mol = -0.38 A(3) per molecule) implying that
      intrahelical hydrogen bonds have a smaller volume than peptide-water hydrogen
      bonds. In contrast, the transition state has a larger volume than either the
      helical or the coil state, with activation volumes of 2.2 cm(3)/mol (3.7 A(3) per
      molecule) for adding and 2.4 cm(3)/mol (4.0 A(3) per molecule) for removing one
      residue. Thus, addition or removal of a helical residue proceeds through a
      transitory high-energy state with a large volume, possibly due to the presence of
      unsatisfied hydrogen bonds, although steric effects may also contribute. 

PMID- 24324161
TI  - Media's role in broadcasting acute stress following the Boston Marathon bombings.
AB  - We compared the impact of media vs. direct exposure on acute stress response to
      collective trauma. We conducted an Internet-based survey following the Boston
      Marathon bombings between April 29 and May 13, 2013, with representative samples
      of residents from Boston (n = 846), New York City (n = 941), and the remainder of
      the United States (n = 2,888). Acute stress symptom scores were comparable in
      Boston and New York [regression coefficient (b) = 0.43; SE = 1.42; 95% confidence
      interval (CI), -2.36, 3.23], but lower nationwide when compared with Boston (b = 
      2.21; SE = 1.07; 95% CI, -4.31, -0.12). Adjusting for prebombing mental health
      (collected prospectively), demographics, and prior collective stress exposure,
      six or more daily hours of bombing-related media exposure in the week after the
      bombings was associated with higher acute stress than direct exposure to the
      bombings (continuous acute stress symptom total: media exposure b = 15.61 vs.
      direct exposure b = 5.69). Controlling for prospectively collected prebombing
      television-watching habits did not change the findings. In adjusted models,
      direct exposure to the 9/11 terrorist attacks and the Sandy Hook School shootings
      were both significantly associated with bombing-related acute stress; Superstorm
      Sandy exposure wasn't. Prior exposure to similar and/or violent events may render
      some individuals vulnerable to the negative effects of collective traumas.
      Repeatedly engaging with trauma-related media content for several hours daily
      shortly after collective trauma may prolong acute stress experiences and promote
      substantial stress-related symptomatology. Mass media may become a conduit that
      spreads negative consequences of community trauma beyond directly affected
      communities. 

PMID- 24324162
TI  - Competing dopamine neurons drive oviposition choice for ethanol in Drosophila.
AB  - The neural circuits that mediate behavioral choice evaluate and integrate
      information from the environment with internal demands and then initiate a
      behavioral response. Even circuits that support simple decisions remain poorly
      understood. In Drosophila melanogaster, oviposition on a substrate containing
      ethanol enhances fitness; however, little is known about the neural mechanisms
      mediating this important choice behavior. Here, we characterize the neural
      modulation of this simple choice and show that distinct subsets of dopaminergic
      neurons compete to either enhance or inhibit egg-laying preference for ethanol
      containing food. Moreover, activity in alpha'beta' neurons of the mushroom body
      and a subset of ellipsoid body ring neurons (R2) is required for this choice. We
      propose a model where competing dopaminergic systems modulate oviposition
      preference to adjust to changes in natural oviposition substrates. 

PMID- 24324163
TI  - Biologically derived melanin electrodes in aqueous sodium-ion energy storage
      devices.
AB  - Biodegradable electronics represents an attractive and emerging paradigm in
      medical devices by harnessing simultaneous advantages afforded by electronically
      active systems and obviating issues with chronic implants. Integrating practical
      energy sources that are compatible with the envisioned operation of transient
      devices is an unmet challenge for biodegradable electronics. Although high
      performance energy storage systems offer a feasible solution, toxic materials and
      electrolytes present regulatory hurdles for use in temporary medical devices.
      Aqueous sodium-ion charge storage devices combined with biocompatible electrodes
      are ideal components to power next-generation biodegradable electronics. Here, we
      report the use of biologically derived organic electrodes composed of melanin
      pigments for use in energy storage devices. Melanins of natural (derived from
      Sepia officinalis) and synthetic origin are evaluated as anode materials in
      aqueous sodium-ion storage devices. Na(+)-loaded melanin anodes exhibit specific
      capacities of 30.4 +/- 1.6 mAhg(-1). Full cells composed of natural melanin
      anodes and lambda-MnO2 cathodes exhibit an initial potential of 1.03 +/- 0.06 V
      with a maximum specific capacity of 16.1 +/- 0.8 mAhg(-1). Natural melanin anodes
      exhibit higher specific capacities compared with synthetic melanins due to a
      combination of beneficial chemical, electrical, and physical properties exhibited
      by the former. Taken together, these results suggest that melanin pigments may
      serve as a naturally occurring biologically derived charge storage material to
      power certain types of medical devices. 

PMID- 24324164
TI  - Restoration of testis function in hypogonadotropic hypogonadal mice harboring a
      misfolded GnRHR mutant by pharmacoperone drug therapy.
AB  - Mutations in receptors, ion channels, and enzymes are frequently recognized by
      the cellular quality control system as misfolded and retained in the endoplasmic
      reticulum (ER) or otherwise misrouted. Retention results in loss of function at
      the normal site of biological activity and disease. Pharmacoperones are target
      specific small molecules that diffuse into cells and serve as folding templates
      that enable mutant proteins to pass the criteria of the quality control system
      and route to their physiologic site of action. Pharmacoperones of the
      gonadotropin releasing hormone receptor (GnRHR) have efficacy in cell culture
      systems, and their cellular and biochemical mechanisms of action are known. Here,
      we show the efficacy of a pharmacoperone drug in a small animal model, a knock-in
      mouse, expressing a mutant GnRHR. This recessive mutation (GnRHR E(90)K) causes
      hypogonadotropic hypogonadism (failed puberty associated with low or apulsatile
      luteinizing hormone) in both humans and in the mouse model described. We find
      that pulsatile pharmacoperone therapy restores E(90)K from ER retention to the
      plasma membrane, concurrently with responsiveness to the endogenous natural
      ligand, gonadotropin releasing hormone, and an agonist that is specific for the
      mutant. Spermatogenesis, proteins associated with steroid transport and
      steroidogenesis, and androgen levels were restored in mutant male mice following
      pharmacoperone therapy. These results show the efficacy of pharmacoperone therapy
      in vivo by using physiological, molecular, genetic, endocrine and biochemical
      markers and optimization of pulsatile administration. We expect that this newly
      appreciated approach of protein rescue will benefit other disorders sharing
      pathologies based on misrouting of misfolded protein mutants. 

PMID- 24324165
TI  - Mutational effects on stability are largely conserved during protein evolution.
AB  - Protein stability and folding are the result of cooperative interactions among
      many residues, yet phylogenetic approaches assume that sites are independent.
      This discrepancy has engendered concerns about large evolutionary shifts in
      mutational effects that might confound phylogenetic approaches. Here we
      experimentally investigate this issue by introducing the same mutations into a
      set of diverged homologs of the influenza nucleoprotein and measuring the effects
      on stability. We find that mutational effects on stability are largely conserved
      across the homologs. We reach qualitatively similar conclusions when we simulate
      protein evolution with molecular-mechanics force fields. Our results do not mean
      that proteins evolve without epistasis, which can still arise even when
      mutational stability effects are conserved. However, our findings indicate that
      large evolutionary shifts in mutational effects on stability are rare, at least
      among homologs with similar structures and functions. We suggest that properly
      describing the clearly observable and highly conserved amino acid preferences at
      individual sites is likely to be far more important for phylogenetic analyses
      than accounting for rare shifts in amino acid propensities due to site
      covariation. 

PMID- 24324166
TI  - Working-memory capacity protects model-based learning from stress.
AB  - Accounts of decision-making have long posited the operation of separate,
      competing valuation systems in the control of choice behavior. Recent theoretical
      and experimental advances suggest that this classic distinction between habitual
      and goal-directed (or more generally, automatic and controlled) choice may arise
      from two computational strategies for reinforcement learning, called model-free
      and model-based learning. Popular neurocomputational accounts of reward
      processing emphasize the involvement of the dopaminergic system in model-free
      learning and prefrontal, central executive-dependent control systems in model
      based choice. Here we hypothesized that the hypothalamic-pituitary-adrenal (HPA)
      axis stress response--believed to have detrimental effects on prefrontal cortex
      function--should selectively attenuate model-based contributions to behavior. To
      test this, we paired an acute stressor with a sequential decision-making task
      that affords distinguishing the relative contributions of the two learning
      strategies. We assessed baseline working-memory (WM) capacity and used salivary
      cortisol levels to measure HPA axis stress response. We found that stress
      response attenuates the contribution of model-based, but not model-free,
      contributions to behavior. Moreover, stress-induced behavioral changes were
      modulated by individual WM capacity, such that low-WM-capacity individuals were
      more susceptible to detrimental stress effects than high-WM-capacity individuals.
      These results enrich existing accounts of the interplay between acute stress,
      working memory, and prefrontal function and suggest that executive function may
      be protective against the deleterious effects of acute stress.

PMID- 24324167
TI  - Stepwise artificial evolution of a plant disease resistance gene.
AB  - Genes encoding plant nucleotide-binding leucine-rich repeat (NB-LRR) proteins
      confer dominant resistance to diverse pathogens. The wild-type potato NB-LRR
      protein Rx confers resistance against a single strain of potato virus X (PVX),
      whereas LRR mutants protect against both a second PVX strain and the distantly
      related poplar mosaic virus (PopMV). In one of the Rx mutants there was a cost to
      the broad-spectrum resistance because the response to PopMV was transformed from
      a mild disease on plants carrying wild-type Rx to a trailing necrosis that killed
      the plant. To explore the use of secondary mutagenesis to eliminate this cost of
      broad-spectrum resistance, we performed random mutagenesis of the N-terminal
      domains of this broad-recognition version of Rx and isolated four mutants with a
      stronger response against the PopMV coat protein due to enhanced activation
      sensitivity. These mutations are located close to the nucleotide-binding pocket,
      a highly conserved structure that likely controls the "switch" between active and
      inactive NB-LRR conformations. Stable transgenic plants expressing one of these
      versions of Rx are resistant to the strains of PVX and the PopMV that previously
      caused trailing necrosis. We conclude from this work that artificial evolution of
      NB-LRR disease resistance genes in crops can be enhanced by modification of both
      activation and recognition phases, to both accentuate the positive and eliminate
      the negative aspects of disease resistance. 

PMID- 24324168
TI  - Visualization of two transfer RNAs trapped in transit during elongation factor G
      mediated translocation.
AB  - During protein synthesis, coupled translocation of messenger RNAs (mRNA) and
      transfer RNAs (tRNA) through the ribosome takes place following formation of each
      peptide bond. The reaction is facilitated by large-scale conformational changes
      within the ribosomal complex and catalyzed by elongtion factor G (EF-G). Previous
      structural analysis of the interaction of EF-G with the ribosome used either
      model complexes containing no tRNA or only a single tRNA, or complexes where EF-G
      was directly bound to ribosomes in the posttranslocational state. Here, we
      present a multiparticle cryo-EM reconstruction of a translocation intermediate
      containing two tRNAs trapped in transit, bound in chimeric intrasubunit ap/P and
      pe/E hybrid states. The downstream ap/P-tRNA is contacted by domain IV of EF-G
      and P-site elements within the 30S subunit body, whereas the upstream pe/E-tRNA
      maintains tight interactions with P-site elements of the swiveled 30S head.
      Remarkably, a tight compaction of the tRNA pair can be seen in this state. The
      translocational intermediate presented here represents a previously missing link
      in understanding the mechanism of translocation, revealing that the ribosome uses
      two distinct molecular ratchets, involving both intra- and intersubunit
      rotational movements, to drive the synchronous movement of tRNAs and mRNA. 

PMID- 24324169
TI  - Whole chromosome gain does not in itself confer cancer-like chromosomal
      instability.
AB  - Constitutional aneuploidy is typically caused by a single-event meiotic or early
      mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic
      tissue, is attributed to continuous chromosomal instability. More debated as a
      cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se
      causes chromosomal instability, for example, in patients with inborn aneuploidy.
      We have addressed this issue by quantifying the level of somatic mosaicism, a
      proxy marker of chromosomal instability, in patients with constitutional
      aneuploidy by precise background-filtered dual-color FISH. In contrast to
      previous studies that used less precise methods, we find that constitutional
      trisomy, even for large chromosomes that are often trisomic in cancer, does not
      confer a significantly elevated rate of somatic chromosomal mosaicism in
      individual cases. Constitutional triploidy was associated with an increased level
      of somatic mosaicism, but this consisted mostly of reversion from trisomy to
      disomy and did not correspond to a proportionally elevated level of chromosome
      mis-segregation in triploids, indicating that the observed mosaicism resulted
      from a specific accumulation of cells with a hypotriploid chromosome number. In
      no case did the rate of somatic mosaicism in constitutional aneuploidy exceed
      that of "chromosomally stable" cancer cells. Our findings show that even though
      constitutional aneuploidy was in some cases associated with low-level somatic
      mosaicism, it was insufficient to generate the cancer-like levels expected if
      aneuploidy single-handedly triggered cancer-like chromosomal instability. 

PMID- 24324170
TI  - Genome differentiation of Drosophila melanogaster from a microclimate contrast in
      Evolution Canyon, Israel.
AB  - The opposite slopes of "Evolution Canyon" in Israel have served as a natural
      model system of adaptation to a microclimate contrast. Long-term studies of
      Drosophila melanogaster populations inhabiting the canyon have exhibited
      significant interslope divergence in thermal and drought stress resistance,
      candidate genes, mobile elements, habitat choice, mating discrimination, and wing
      shape variation, all despite close physical proximity of the contrasting
      habitats, as well as substantial interslope migration. To examine patterns of
      genetic differentiation at the genome-wide level, we used high coverage
      sequencing of the flies' genomes. A total of 572 genes were significantly
      different in allele frequency between the slopes, 106 out of which were
      associated with 74 significantly overrepresented gene ontology (GO) terms,
      particularly so with response to stimulus and developmental and reproductive
      processes, thus corroborating previous observations of interslope divergence in
      stress response, life history, and mating functions. There were at least 37
      chromosomal "islands" of interslope divergence and low sequence polymorphism,
      plausible signatures of selective sweeps, more abundant in flies derived from one
      (north-facing) of the slopes. Positive correlation between local recombination
      rate and the level of nucleotide polymorphism was also found. 

PMID- 24324171
TI  - Reproducible copy number variation patterns among single circulating tumor cells
      of lung cancer patients.
AB  - Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and
      seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis
      or even diagnosis, but has been hampered by low single-cell genome coverage of
      scarce CTCs. Here, we report the use of the recently developed multiple annealing
      and looping-based amplification cycles for whole-genome amplification of single
      CTCs from lung cancer patients. We observed characteristic cancer-associated
      single-nucleotide variations and insertions/deletions in exomes of CTCs. These
      mutations provided information needed for individualized therapy, such as drug
      resistance and phenotypic transition, but were heterogeneous from cell to cell.
      In contrast, every CTC from an individual patient, regardless of the cancer
      subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to
      those of the metastatic tumor of the same patient. Interestingly, different
      patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV
      patterns in their CTCs. Even more interestingly, patients of small-cell lung
      cancer have CNV patterns distinctly different from those of ADC patients. Our
      finding suggests that CNVs at certain genomic loci are selected for the
      metastasis of cancer. The reproducibility of cancer-specific CNVs offers
      potential for CTC-based cancer diagnostics. 

PMID- 24324172
TI  - Genetically encoded fluorescent probe to visualize intracellular
      phosphatidylinositol 3,5-bisphosphate localization and dynamics.
AB  - Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance
      phosphoinositide presumed to be localized to endosomes and lysosomes, where it
      recruits cytoplasmic peripheral proteins and regulates endolysosome-localized
      membrane channel activity. Cells lacking PI(3,5)P2 exhibit lysosomal trafficking
      defects, and human mutations in the PI(3,5)P2-metabolizing enzymes cause lysosome
      related diseases. The spatial and temporal dynamics of PI(3,5)P2, however, remain
      unclear due to the lack of a reliable detection method. Of the seven known
      phosphoinositides, only PI(3,5)P2 binds, in the low nanomolar range, to a
      cytoplasmic phosphoinositide-interacting domain (ML1N) to activate late endosome
      and lysosome (LEL)-localized transient receptor potential Mucolipin 1 (TRPML1)
      channels. Here, we report the generation and characterization of a PI(3,5)P2
      specific probe, generated by the fusion of fluorescence tags to the tandem
      repeats of ML1N. The probe was mainly localized to the membranes of Lamp1
      positive compartments, and the localization pattern was dynamically altered by
      either mutations in the probe, or by genetically or pharmacologically
      manipulating the cellular levels of PI(3,5)P2. Through the use of time-lapse live
      cell imaging, we found that the localization of the PI(3,5)P2 probe was regulated
      by serum withdrawal/addition, undergoing rapid changes immediately before
      membrane fusion of two LELs. Our development of a PI(3,5)P2-specific probe may
      facilitate studies of both intracellular signal transduction and membrane
      trafficking in the endosomes and lysosomes. 

PMID- 24324173
TI  - The signaling network that silences the spindle assembly checkpoint upon the
      establishment of chromosome bipolar attachment.
AB  - Improper kinetochore attachments activate the spindle assembly checkpoint (SAC)
      to prevent anaphase onset, but it is poorly understood how this checkpoint is
      silenced to allow anaphase onset. Chromosome bipolar attachment applies tension
      on sister kinetochores, and the lack of tension delays anaphase onset. In budding
      yeast, the delay induced by tension defects depends on the intact SAC as well as
      increase in ploidy (Ipl1)/Aurora kinase and a centromere-associated protein
      ShuGOshin (Sgo1). Here we provide evidence indicating that Ipl1-dependent
      phosphorylation of the kinetochore protein Duo1 and Mps1 interacting (Dam1)
      prevents SAC silencing when tension is absent. The nonphosphorylatable dam1
      mutant cells, as well as sgo1 mutant cells, are competent in SAC activation but
      unable to prevent SAC silencing in response to tension defects. We further found
      that phosphomimetic dam1 mutants exhibited delayed anaphase onset mainly due to
      the failure in SAC silencing, but destabilized kinetochore attachment likely
      plays a minor role in this delay. Because the tension resulting from bipolar
      attachment triggers the dephosphorylation of Dam1 by protein phosphatase 1, this
      dephosphorylation likely coordinates SAC silencing with chromosome bipolar
      attachment. Therefore, Sgo1, Ipl1 kinase, Dam1, and protein phosphatase 1
      comprise the SAC silencing network that ensures the correct timing for anaphase
      onset. 

PMID- 24324175
TI  - Evidence for soft bounds in Ubuntu package sizes and mammalian body masses.
AB  - The development of a complex system depends on the self-coordinated action of a
      large number of agents, often determining unexpected global behavior. The case of
      software evolution has great practical importance: knowledge of what is to be
      considered atypical can guide developers in recognizing and reacting to abnormal
      behavior. Although the initial framework of a theory of software exists, the
      current theoretical achievements do not fully capture existing quantitative data
      or predict future trends. Here we show that two elementary laws describe the
      evolution of package sizes in a Linux-based operating system: first, relative
      changes in size follow a random walk with non-Gaussian jumps; second, each size
      change is bounded by a limit that is dependent on the starting size, an
      intriguing behavior that we call "soft bound." Our approach is based on data
      analysis and on a simple theoretical model, which is able to reproduce empirical
      details without relying on any adjustable parameter and generates definite
      predictions. The same analysis allows us to formulate and support the hypothesis
      that a similar mechanism is shaping the distribution of mammalian body sizes, via
      size-dependent constraints during cladogenesis. Whereas generally accepted
      approaches struggle to reproduce the large-mass shoulder displayed by the
      distribution of extant mammalian species, this is a natural consequence of the
      softly bounded nature of the process. Additionally, the hypothesis that this
      model is valid has the relevant implication that, contrary to a common
      assumption, mammalian masses are still evolving, albeit very slowly. 

PMID- 24324174
TI  - Awake reactivation predicts memory in humans.
AB  - How are new experiences transformed into memories? Recent findings have shown
      that activation in brain regions involved in the initial task performance
      reemerges during postlearning rest, suggesting that "offline activity" might be
      important for this transformation. It is unclear, however, whether such offline
      activity indeed reflects reactivation of individual learning experiences, whether
      the amount of event-specific reactivation is directly related to later memory
      performance, and what brain regions support such event-specific reactivation.
      Here, we used functional magnetic resonance imaging to assess whether event
      specific reactivation occurs spontaneously during an active, postlearning delay
      period in the human brain. Applying representational similarity analysis, we
      found that successful recall of individual study events was predicted by the
      degree of their endogenous reactivation during the delay period. Within the
      medial temporal lobe, this reactivation was observed in the entorhinal cortex.
      Beyond the medial temporal lobe, event-specific reactivation was found in the
      retrosplenial cortex. Controlling for the levels of blood oxygen level-dependent
      activation and the serial position during encoding, the data suggest that offline
      reactivation might be a key mechanism for bolstering episodic memory beyond
      initial study processes. These results open a unique avenue for the systematic
      investigation of reactivation and consolidation of episodic memories in humans. 

PMID- 24324176
TI  - Role of Loc1p in assembly and reorganization of nuclear ASH1 messenger
      ribonucleoprotein particles in yeast.
AB  - Directional transport of mRNA is a universal feature in eukaryotes, requiring the
      assembly of motor-dependent RNA-transport particles. The cytoplasmic transport of
      mRNAs is preceded by the nuclear assembly of pre-messenger ribonucleoprotein
      particles (mRNPs). In budding yeast, the asymmetric synthesis of HO 1 (ASH1) pre
      mRNP originates already cotranscriptionally and passes through the nucleolus
      before its nuclear export. The nucleolar localization of ASH1 mRNA protein 1
      (Loc1p) is required for efficient ASH1 mRNA localization. Immunoprecipitation
      experiments have revealed that Loc1p forms cocomplexes with other components of
      the ASH1 transport complex. However, it remains unclear how Loc1p is recruited
      into this mRNP and why Loc1p is important for ASH1 mRNA localization. Here we
      demonstrate that Loc1p undergoes a direct and specific interaction with the ASH1
      mRNA-binding Swi5p-dependent HO expression protein 2 (She2p). This cocomplex
      shows higher affinity and specificity for RNA bearing localization elements than
      the individual proteins. It also stabilizes the otherwise transient binding of
      She2p to ASH1 mRNA, suggesting that cooperative mRNA binding of Loc1p with She2p
      is the required nuclear function of Loc1p for ASH1 mRNA localization. After
      nuclear export, myosin-bound She3p joins the ASH1 mRNP to form a highly specific
      cocomplex with She2p and ASH1 mRNA. Because Loc1p is found only in the nucleus,
      it must be removed from the complex directly before or after export. In vitro and
      in vivo experiments indicate that the synergistic interaction of She2p and She3p
      displaces Loc1p from the ASH1 complex, allowing free Loc1p to rapidly reenter the
      nucle(ol)us. Together these findings suggest an ordered process of nuclear
      assembly and reorganization for the maturation of localizing ASH1 mRNPs. 

PMID- 24324192
TI  - Creating a safe, reliable hospital at night handover: a case study in
      implementation science.
AB  - BACKGROUND: We developed protocols to handover patients from day to hospital at
      night (H@N) teams. SETTING: NHS paediatric specialist hospital. METHOD: We
      observed four handover protocols (baseline, Phases 1, 2 and 3) over 2 years. A
      mixed-method study (observation, interviews, task analysis, prospective risk
      assessment, document and case note review) explored the impact of different
      protocols on performance. INTERVENTION: In Phase 1, a handover protocol was
      introduced to resolve problems with the baseline H@N handover. Following this
      intervention, two further revisions to the handover occurred, driven by staff
      feedback (Phases 2 and 3). RESULTS: Variations in performance between handover
      protocols on three process measures, start time efficiency, total length of
      handover, and number of distractions and interruptions, were identified.
      Univariate regression analysis showed statistically significant differences
      between handover protocols on two surrogate outcome measures: number of flagging
      omissions and the number of out of hours deteriorations (p=0.04 for Phase 3 vs
      Phase 1 for both measures (CI 1.04 to 4.08; CI 1.03 to 4.33), and for Phase 3 vs
      Phase 2 (p=0.006 and p=0.001 (CI 1.22 to 5.15; CI 1.62 to 9.0)), respectively).
      The Phase 1 and 2 handover protocols were effective at identifying patients whose
      clinical condition warranted review overnight. Performance on both surrogate
      outcome measures, length of handover and distractions, deteriorated in Phase 3.
      CONCLUSIONS: A carefully designed prioritisation process within the H@N handover
      can be effective at flagging acutely unwell patients. However, the protocol we
      introduced was unsustainable. In a complex healthcare system, sustainable
      implementation of new processes may be threatened by conflicting goals.

PMID- 24324193
TI  - An in vivo study of hindfoot 3D kinetics in stage II posterior tibial tendon
      dysfunction (PTTD) flatfoot based on weight-bearing CT scan.
AB  - OBJECTIVE: The objective of this study was to evaluate the rotation and
      translation of each joint in the hindfoot and compare the load response in
      healthy feet with that in stage II posterior tibial tendon dysfunction (PTTD)
      flatfoot by analysing the reconstructive three-dimensional (3D) computed
      tomography (CT) image data during simulated weight-bearing. METHODS: CT scans of
      15 healthy feet and 15 feet with stage II PTTD flatfoot were taken first in a non
      weight-bearing condition, followed by a simulated full-body weight-bearing
      condition. The images of the hindfoot bones were reconstructed into 3D models.
      The 'twice registration' method in three planes was used to calculate the
      position of the talus relative to the calcaneus in the talocalcaneal joint, the
      navicular relative to the talus in talonavicular joint, and the cuboid relative
      to the calcaneus in the calcaneocuboid joint. RESULTS: From non- to full-body
      weight-bearing condition, the difference in the talus position relative to the
      calcaneus in the talocalcaneal joint was 0.6 degrees  more dorsiflexed (p =
      0.032), 1.4 degrees  more everted (p = 0.026), 0.9 mm more anterior (p = 0.031)
      and 1.0 mm more proximal (p = 0.004) in stage II PTTD flatfoot compared with that
      in a healthy foot. The navicular position difference relative to the talus in the
      talonavicular joint was 3 degrees  more everted (p = 0.012), 1.3 mm more lateral
      (p = 0.024), 0.8 mm more anterior (p = 0.037) and 2.1 mm more proximal (p =
      0.017). The cuboid position difference relative to the calcaneus in the
      calcaneocuboid joint did not change significantly in rotation and translation
      (all p >= 0.08). CONCLUSION: Referring to a previous study regarding both the
      cadaveric foot and the live foot, joint instability occurred in the hindfoot in
      simulated weight-bearing condition in patients with stage II PTTD flatfoot. The
      method used in this study might be applied to clinical analysis of the aetiology
      and evolution of PTTD flatfoot, and may inform biomechanical analyses of the
      effects of foot surgery in the future. Cite this article: Bone Joint Res
      2013;2:255-63.

PMID- 24324191
TI  - Interleukin-17A enhances host defense against cryptococcal lung infection through
      effects mediated by leukocyte recruitment, activation, and gamma interferon
      production.
AB  - Infection of C57BL/6 mice with the moderately virulent Cryptococcus neoformans
      strain 52D models the complex adaptive immune response observed in HIV-negative
      patients with persistent fungal lung infections. In this model, Th1 and Th2
      responses evolve over time, yet the contribution of interleukin-17A (IL-17A) to
      antifungal host defense is unknown. In this study, we show that fungal lung
      infection promoted an increase in Th17 T cells that persisted to 8 weeks
      postinfection. Our comparison of fungal lung infection in wild-type mice and IL
      17A-deficient mice (IL-17A(-/-) mice; C57BL/6 genetic background) demonstrated
      that late fungal clearance was impaired in the absence of IL-17A. This finding
      was associated with reduced intracellular containment of the organism within lung
      macrophages and deficits in the accumulation of total lung leukocytes, including
      specific reductions in CD11c+ CD11b+ myeloid cells (dendritic cells and exudate
      macrophages), B cells, and CD8+ T cells, and a nonsignificant trend in the
      reduction of lung neutrophils. Although IL-17A did not alter the total number of
      CD4 T cells, decreases in the total number of CD4 T cells and CD8 T cells
      expressing gamma interferon (IFN-gamma) were observed in IL-17A(-/-) mice.
      Lastly, expression of major histocompatibility complex class II (MHC-II) and the
      costimulatory molecules CD80 and CD86 on CD11c+ CD11b+ myeloid cells was
      diminished in IL-17A(-/-) mice. Collectively, these data indicate that IL-17A
      enhances host defenses against a moderately virulent strain of C. neoformans
      through effects on leukocyte recruitment, IFN-gamma production by CD4 and CD8 T
      cells, and the activation of lung myeloid cells.

PMID- 24324194
TI  - Should suspected cervical spinal cord injuries be immobilised? A systematic
      review protocol.
AB  - BACKGROUND: Cervical spinal cord injuries may result in life-threatening
      situations and long-term disability. Prehospital spinal immobilisation is the
      standard of care for patients with potential spinal cord injury (SCI). It aims to
      prepare patients for transport, achieve neutral spinal alignment, and reduce
      movement and secondary injuries in potentially unstable spines. However, there is
      a lack of evidence on its clinical benefits and its overall effect on patient
      outcomes. OBJECTIVES: To identify the reported outcomes following immobilisation
      of suspected cervical SCI, to compare the effects of spinal immobilisation versus
      no immobilisation on the reported outcomes, and to provide recommendations for
      prehospital cervical immobilisation. DESIGN/METHODS: A search of the literature
      will be conducted using relevant online databases. This will include all types of
      human studies that were published in English from the earliest record available
      to the first week of October 2013. One author will conduct the search and two
      independent authors will screen the titles and the abstracts identified by the
      search and critically appraise the selected papers. A third author will be
      available to resolve any disagreement. The findings will be reported according to
      Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. Critical
      appraisal as well as the level and the strength of evidence will follow the
      National Health and Medical Research Council (NHMRC) guidelines. DISCUSSION:
      Evidence-based practices should be pursued to further improve the prehospital
      care for suspected cervical SCI. This systematic review will contribute to the
      body of knowledge regarding the spinal immobilisation effects on the SCI
      patient's outcomes.

PMID- 24324195
TI  - Child passenger safety practices and injury risk in crashes with father versus
      mother drivers.
AB  - In order to test stereotypes that mothers are more safety conscious than fathers,
      this study aimed to explore differences in restraint patterns, front-row seating
      and injury for children in crashes when driven by fathers versus mothers, both
      when driving alone and with other adults. From 15 January 2003 to 30 November
      2007, data were collected via insurance claims records and telephone surveys on a
      weighted sample of 10,715 child passengers in crashes. When riding with children
      and no other adults, father drivers in crashes were more likely than mother
      drivers to transport children <9 years old unrestrained or suboptimally
      restrained (35.0% vs 26.1%, p=0.001) and to seat children <13 years old in the
      front row (23.7% vs 14.3%, p<0.001). For children <16 years, no statistically
      significant difference in injury risk was noted for father versus mother drivers,
      regardless of adult passenger presence. Further improvements in child passenger
      safety might be gained with campaigns directed at both fathers and mothers.

PMID- 24324196
TI  - Sense and sensitivity.

PMID- 24324197
TI  - Diagnosing concussion.

PMID- 24324198
TI  - Diagnosing concussion.

PMID- 24324199
TI  - Diagnosing concussion.

PMID- 24324200
TI  - Reflections. Seasonal gifts.

PMID- 24324201
TI  - Unsubstantiated theory. The story of a physician, his bowels and beer.

PMID- 24324202
TI  - Satire. The metamorphosis.

PMID- 24324205
TI  - Derivation of sperm from xenografted testis cells and tissues of the peccary
      (Tayassu tajacu).
AB  - Because the collared peccary (Tayassu tajacu) has a peculiar Leydig cell
      cytoarchitecture, this species represents a unique mammalian model for
      investigating testis function. Taking advantage of the well-established and very
      useful testis xenograft technique, in the present study, testis tissue and testis
      cell suspensions from immature collared peccaries (n=4; 3 months old) were
      xenografted in SCID mice (n=48) and evaluated at 2, 4, 6, and 8 months after
      grafting. Complete spermatogenesis was observed at 6 and 8 months after testis
      tissue xenografting. However, probably due to de novo testis morphogenesis and
      low androgen secretion, functionally evaluated by the seminal vesicle weight, a
      delay in spermatogenesis progression was observed in the testis cell suspension
      xenografts, with the production of fertile sperm only at 8 months after grafting.
      Importantly, demonstrating that the peculiar testicular cytoarchitecture of the
      collared peccary is intrinsically programmed, the unique Leydig cell arrangement
      observed in this species was re-established after de novo testis morphogenesis.
      The sperm collected from the xenografts resulted in diploid embryos that
      expressed the paternally imprinted gene NNAT after ICSI. The present study is the
      first to demonstrate complete spermatogenesis with the production of fertile
      sperm from testis cell suspension xenografts in a wild mammalian species.
      Therefore, due to its unique testicular cytoarchitecture, xenograft techniques,
      particularly testis cell suspensions, may represent a new and very promising
      approach to evaluate testis morphogenesis and to investigate spermatogonial stem
      cell physiology and niche in the collared peccary. 

PMID- 24324206
TI  - 2-arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression
      and apoptosis in BeWo cells.
AB  - The major endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a member of the
      endocannabinoid system (ECS) that participates in cell proliferation and
      apoptosis, important events for the homoeostasis of biological systems. The
      formation of placenta is one of the most important stages of pregnancy and its
      development requires highly regulated proliferation, differentiation and
      apoptosis of trophoblasts. Anomalies in these processes are associated with
      gestational pathologies. In this work, we aimed to study the involvement of 2-AG
      in cytotrophoblast cell turnover. We found that 2-AG biosynthetic (diacylglycerol
      lipase A) and degradative (monoacylglycerol lipase) enzymes are expressed in
      human cytotrophoblasts and in BeWo cells. We also found that 2-AG induces a
      decrease in cell viability in a time- and concentration-dependent manner and
      exerts antiproliferative effects. The loss of cell viability induced by a 48-h
      treatment with 2-AG (10 MUM) was accompanied by chromatin fragmentation and
      condensation, morphological features of apoptosis. Additionally, 2-AG induced an
      increase in caspase 3/7 and 9 activities, a loss of mitochondrial membrane
      potential (Deltapsim) and an increase in reactive oxygen species (ROS)/reactive
      nitrogen species (RNS) generation, suggesting the activation of the mitochondrial
      pathway. Moreover, whereas Deltapsim loss and ROS/RNS generation were
      significantly attenuated by the antagonists of both the cannabinoid receptors 1
      and 2 (CB1 and CB2), the increase in caspase 3/7 and 9 activities and loss of
      cell viability were reversed only by the antagonist of CB2 receptor; the blockage
      of the eCB membrane transporter and the depletion of cholesterol failed to
      reverse the effects of 2-AG. Therefore, this work supports the importance of
      cannabinoid signalling during cytotrophoblast cell turnover and that its
      deregulation may be responsible for altered placental development and poor
      pregnancy outcomes. 

PMID- 24324207
TI  - Is the lack of physical activity strategy for children complicit mass child
      neglect?

PMID- 24324208
TI  - Foxp3+ T(reg) cells in humoral immunity.
AB  - T(reg) cells are essential for the maintenance of immune homeostasis and
      prevention of autoimmunity. In humoral immune responses, loss of T(reg) cell
      function causes increased levels of serum autoantibodies, hyper-IgE, spontaneous
      generation of germinal centres, and enhanced numbers of specialised T follicular
      helper cells (T(fh) cells) controlled by the lineage-defining transcription
      factor BCL-6 (B-cell lymphoma 6). Recent studies have demonstrated that a subset
      of T(reg) cells [T follicular regulatory (T(freg)) cells] are able to co-opt the
      follicular T-cell program by gaining expression of BCL-6 and travelling to the
      follicle where they have an important role in the control of expansion of T(fh)
      cells and the germinal centre reaction. However, the mechanisms by which they
      exert this control are still under investigation. In this review, we discuss the
      effects of T(reg) cells on humoral immunity and the mechanisms by which they
      exert their regulatory function.

PMID- 24324209
TI  - Time-resolved characterization of cAMP/PKA-dependent signaling reveals that
      platelet inhibition is a concerted process involving multiple signaling pathways.
AB  - One of the most important physiological platelet inhibitors is endothelium
      derived prostacyclin which stimulates the platelet cyclic adenosine
      monophosphate/protein kinase A (cAMP/PKA)-signaling cascade and inhibits
      virtually all platelet-activating key mechanisms. Using quantitative mass
      spectrometry, we analyzed time-resolved phosphorylation patterns in human
      platelets after treatment with iloprost, a stable prostacyclin analog, for 0, 10,
      30, and 60 seconds to characterize key mediators of platelet inhibition and
      activation in 3 independent biological replicates. We quantified over 2700
      different phosphorylated peptides of which 360 were significantly regulated upon
      stimulation. This comprehensive and time-resolved analysis indicates that
      platelet inhibition is a multipronged process involving different kinases and
      phosphatases as well as many previously unanticipated proteins and pathways. 

PMID- 24324210
TI  - EU air quality limits are not stringent enough, say researchers.

PMID- 24324211
TI  - CX3CL1 and CX3CR1 expression in tertiary lymphoid structures in salivary gland
      infiltrates: fractalkine contribution to lymphoid neogenesis in Sjogren's
      syndrome.
AB  - OBJECTIVES: Primary SS is an autoimmune disease characterized by chronic
      lymphocytic inflammation and ectopic germinal centre (GC) formation within
      salivary glands. Fractalkine (CX3CL1), associated with the pathogenesis of RA, is
      the sole member of the CX3C chemokine (CK) family and acts as an adhesion and
      chemotactic molecule. The objectives of this work are to determine to what extent
      CX3CL1 and its receptor CX3CR1 expression might be altered in salivary glands
      obtained from patients and to establish whether these CKs might be involved in SS
      ectopic lymphoneogenesis. METHODS: We assessed the presence of CX3CL1 protein in
      sera by ELISA in 21 patients with primary SS, 11 patients with Sicca syndrome
      (Sicca), 20 RA patients and 10 blood donors. Histological evaluation was
      performed on sequential sections of salivary gland tissue. Using TaqMan RT-PCR we
      studied CX3CL1 and CX3CR1 mRNA expression in salivary gland tissues from a
      molecular point of view. RESULTS: Increased serum levels of CX3CL1 protein were
      observed in SS patients compared with controls (P < 0.0001) and in RA patients
      compared with controls (P < 0.0001), but no difference was found between Sicca
      patients and controls (P = 0.22). We identified histologically the cells
      expressing CX3CL1 and CX3CR1 in salivary glands of SS patients and we localized
      the molecule within tertiary lymphoid structures. Finally, the mRNA levels of the
      CK and its receptor were up-regulated in SS salivary glands. CONCLUSION: We
      believe that our findings point to the need for future studies on CX3CL1 and
      CX3CR1 proteins as contributors to the formation of ectopic GCs and possibly as a
      new tool in the evaluation and diagnosis of SS.

PMID- 24324212
TI  - Global prevalence of ankylosing spondylitis.
AB  - OBJECTIVES: For effective health care provision, knowledge of disease prevalence
      is paramount. There has been no systematic endeavour to establish continent-based
      AS estimates, however, prevalence is thought to vary by country and background
      HLA-B27 prevalence. This study aimed to estimate AS prevalence worldwide and to
      calculate the expected number of cases. METHODS: A systematic literature search
      was conducted. Prevalence data were extracted and used to calculate the mean
      prevalence by continent and the expected number of cases based on country
      specific prevalence (or, if missing, the prevalence from neighbouring countries).
      A second estimate was made using the prevalence from countries with similar HLA
      B27 prevalences if a country-specific prevalence estimate was not available.
      RESULTS: The mean AS prevalence per 10,000 (from 36 eligible studies) was 23.8 in
      Europe, 16.7 in Asia, 31.9 in North America, 10.2 in Latin America and 7.4 in
      Africa. Additional estimates, weighted by study size, were calculated as 18.6,
      18.0 and 12.2 for Europe, Asia and Latin America, respectively. There were
      sufficient studies to estimate the number of cases in Europe and Asia, calculated
      to be 1.30-1.56 million and 4.63-4.98 million, respectively. CONCLUSION: This
      study represents the first systematic attempt to collate estimates of AS
      prevalence into a single continent-based estimate. In addition, the number of
      expected cases in Europe and Asia was estimated. Through reviewing the current
      literature, it is apparent that the continuing conduct of epidemiological studies
      of AS prevalence is of great importance, particularly as diagnostic capabilities
      improve and with the recent development of the criteria for axial SpA.

PMID- 24324213
TI  - Childhood inflammatory brain diseases: pathogenesis, diagnosis and therapy.
AB  - Inflammatory brain diseases (IBrainDs) are a leading cause of devastating
      neurological deficits or neuropsychiatric syndromes in previously healthy
      children. The spectrum is expanding rapidly and new disease entities have been
      discovered in the last decade. IBrainD can occur as a primary disease or may
      occur secondary to an underlying cause. This review focuses on the clinical
      presentation, diagnostic features, pathology and histology characteristics and
      treatment of the primary childhood IBrainDs. 

PMID- 24324214
TI  - Treating pain in patients with drug-dependence problems.

PMID- 24324215
TI  - Tick bite prevention and tick removal.

PMID- 24324216
TI  - Imported measles and rubella pose threat to US elimination of the diseases, says
      CDC report.

PMID- 24324217
TI  - Widow takes fertility agency to court over storage of husband's sperm.

PMID- 24324218
TI  - Government policy is damaging people most vulnerable to alcohol misuse, warns
      leading doctor.

PMID- 24324219
TI  - Care is needed in epidemiological research not to overgeneralise about cancer
      diagnosis and treatment.

PMID- 24324221
TI  - Dynamics of the pneumococcal population causing acute exacerbations in COPD
      patients in a Barcelona hospital (2009-12): comparison with 2001-04 and 2005-08
      periods.
AB  - BACKGROUND: Pneumococci are an important cause of acute exacerbations in patients
      with chronic obstructive pulmonary disease (COPD). In the last decade, the
      pneumococcal population has changed, mainly due to the introduction of the 7
      valent conjugate vaccine (PCV7). METHODS: We analysed the antimicrobial
      susceptibility (microdilution), serotype (PCR) and genotype (PFGE/multilocus
      sequence typing) of pneumococci causing acute exacerbations during the period
      2009-12. Results were compared with two previously published historic periods
      (2001-04 and 2005-08). RESULTS: A total of 206 pneumococci were collected from
      162 COPD patients with acute exacerbations. Compared with previous periods, no
      significant changes in the rate of multidrug resistance were observed (36.2% in
      the 2001-04 period to 33.5% in the 2009-12 period, P = 0.644). The most frequent
      serotypes in the 2009-12 period were 15A (9.6%), 3 (8.1%), 19F (6.6%), 11A (6.1%)
      and 6C (5.6%), which accounted for 36.0%. A drastic decrease in PCV7 serotypes
      was observed throughout the study period (from 39.7% in 2001-04 to 10.9% in 2009
      12, P < 0.001); non-PCV13 serotypes increased from 44.9% to 71.2%, especially 15A
      (from 2.2% to 9.6%) and 6C (from 0.0% to 5.6%) (P < 0.05). The most frequent
      genotypes (clonal complexes, CCs) in the 2009-12 period were CC63(15A,19F,15F)
      (9.1%), CC180(3) (4.5%), CC62(11A) (4.0%), CC97(10A) (4.0%), CC386(6C) (3.5%),
      CC260(3) (3.5%) and CC30(16F) (3.5%). Serotypes 19F, 19A, 6A and 6C were
      genetically diverse. CONCLUSIONS: PCV7 serotypes have decreased dramatically. In
      parallel, two non-PCV7 serotypes (15A and 6C) and their related genotypes (CC63
      and CC386) showed a significant increase. Although resistance rates to beta
      lactams decreased over time, multidrug resistance remained stable.

PMID- 24324222
TI  - Identification of a novel vga(E) gene variant that confers resistance to
      pleuromutilins, lincosamides and streptogramin A antibiotics in staphylococci of
      porcine origin.
AB  - OBJECTIVES: To investigate the genetic basis of pleuromutilin resistance in
      coagulase-negative staphylococci of porcine origin that do not carry known
      pleuromutilin resistance genes and to determine the localization and genetic
      environment of the identified resistance gene. METHODS: Plasmid DNA of two
      pleuromutilin-resistant Staphylococcus cohnii and Staphylococcus simulans
      isolates was transformed into Staphylococcus aureus RN4220. The identified
      resistance plasmids were sequenced completely. The candidate gene for
      pleuromutilin resistance was cloned into shuttle vector pAM401. S. aureus RN4220
      transformants carrying this recombinant shuttle vector were tested for their
      MICs. RESULTS: S. cohnii isolate SA-7 and S. simulans isolate SSI1 carried the
      same plasmid of 5584 bp, designated pSA-7. A variant of the vga(E) gene was
      detected, which encodes a 524 amino acid ATP-binding cassette protein. The
      variant gene shared 85.7% nucleotide sequence identity and the variant protein
      85.3% amino acid sequence identity with the original vga(E) gene and Vga(E)
      protein, respectively. The Vga(E) variant conferred cross-resistance to
      pleuromutilins, lincosamides and streptogramin A antibiotics. Plasmid pSA-7
      showed an organization similar to that of the apmA-carrying plasmid pKKS49 from
      methicillin-resistant S. aureus and the dfrK-carrying plasmid pKKS966 from
      Staphylococcus hyicus. Sequence comparisons suggested that recombination events
      may have played a role in the acquisition of this vga(E) variant. CONCLUSIONS: A
      novel vga(E) gene variant was identified, which was located on a small plasmid
      and was not associated with the transposon Tn6133 [in contrast to the original
      vga(E) gene]. The plasmid location may enable its further dissemination to other
      staphylococci and possibly also to other bacteria.

PMID- 24324224
TI  - Antibiotics and hospital-acquired Clostridium difficile infection: update of
      systematic review and meta-analysis.
AB  - OBJECTIVES: To update the evidence for associations between antibiotic classes
      and hospital-acquired Clostridium difficile infection (HA-CDI). METHODS:
      Electronic databases of journal articles, scholarly theses and conference
      proceedings using subject headings and keywords related to CDI and antibiotic
      exposure were searched. Observational epidemiological studies measuring
      associations between antibiotic classes and HA-CDI were eligible for inclusion.
      Pooled ORs and 95% CIs were calculated using a random effects model. Study
      factors identified a priori were examined as sources of heterogeneity. The
      quality of the studies was assessed using the Newcastle-Ottawa Scale. RESULTS: Of
      569 citations identified, 13 case-control and 1 cohort study (15,938 patients)
      were included. The strongest associations were found for third-generation
      cephalosporins (OR = 3.20, 95% CI = 1.80-5.71; n = 6 studies; I(2) = 79.2%),
      clindamycin (2.86, 2.04-4.02; n = 6; I(2) = 28.5%), second-generation
      cephalosporins (2.23, 1.47-3.37; n = 6; I(2)  = 48.4%), fourth-generation
      cephalosporins (2.14, 1.30-3.52; n = 2; I(2)  = 0.0%), carbapenems (1.84, 1.26
      2.68; n = 6; I(2) = 0.0%), trimethoprim/sulphonamides (1.78, 1.04-3.05; n = 5;
      I(2) = 70%), fluoroquinolones (1.66, 1.17-2.35; n = 10; I(2) = 64%) and
      penicillin combinations (1.45, 1.05-2.02; n = 6; I(2) = 54%). The study
      population and the timing of measurement of antibiotic exposure were the most
      common sources of heterogeneity. Study quality scored high for seven studies,
      moderate for six studies and low for one study. CONCLUSIONS: The risk of HA-CDI
      remains greatest for cephalosporins and clindamycin, and their importance as
      inciting agents should not be minimized. The importance of fluoroquinolones
      should not be overemphasized, particularly if fluoroquinolone-resistant epidemic
      strains of C. difficile are absent.

PMID- 24324223
TI  - Evolution and genetic diversity of the Spain23F-ST81 clone causing adult invasive
      pneumococcal disease in Barcelona (1990-2012).
AB  - OBJECTIVES: We aimed to analyse the clinical epidemiology and genetic diversity
      of invasive pneumococcal disease (IPD) episodes attributed to the Spain(23F)-ST81
      (PMEN1) clone. METHODS: Fifty-eight (2.7%) of 2117 invasive pneumococci isolated
      from adult patients during the 1990-2012 period shared a PFGE pattern related to
      the PMEN1 clone. The genotype was confirmed by multilocus sequence typing. The
      pbp2x, pbp1a, pbp2b and pspA genes were PCR-amplified and sequenced.
      Polymorphisms in the pspC gene were identified by PCR restriction fragment length
      polymorphism. The presence of transposons with erythromycin and tetracycline
      resistance determinants was detected by PCR. RESULTS: The prevalence of the PMEN1
      clone increased from 0.8% in 1991 to 6.2% in 2001, and decreased to 0% in 2010
      12, concomitant with the introduction of the seven-valent pneumococcal conjugate
      vaccine for children. A total of 93.1% of patients had pneumonia, meningitis or
      peritonitis; 87.9% of patients had associated underlying diseases, mainly cancer,
      chronic obstructive pulmonary disease and diabetes. Two closely related sequence
      types (STs) (ST81, n = 52; ST85, n = 6) were detected, with different serotypes:
      23F (n = 42), 19A (n = 9) and 19F (n = 6). All the isolates were resistant to
      penicillin, co-trimoxazole and chloramphenicol. All the isolates also shared the
      same pbp1a allele, whereas multiple alleles of pbp2b, pbp2x, pspA and pspC were
      detected. Of the isolates, 89.7% were tetracycline resistant and 60.3% (n = 35)
      were macrolide resistant, and resistance was associated with different Tn916-like
      transposons. CONCLUSIONS: Adult IPD caused by this clone was mainly detected in
      patients with underlying conditions, and genetic variability was observed among
      PMEN1 isolates collected in our area over the past 20 years.

PMID- 24324226
TI  - Barriers to working in medicine and teaching after retirement.

PMID- 24324227
TI  - Whose role is it to collect patients' stories?

PMID- 24324225
TI  - Suppression of type 1 pilus assembly in uropathogenic Escherichia coli by
      chemical inhibition of subunit polymerization.
AB  - OBJECTIVES: To identify and to characterize small-molecule inhibitors that target
      the subunit polymerization of the type 1 pilus assembly in uropathogenic
      Escherichia coli (UPEC). METHODS: Using an SDS-PAGE-based assay, in silico pre
      filtered small-molecule compounds were screened for specific inhibitory activity
      against the critical subunit polymerization step of the chaperone-usher pathway
      during pilus biogenesis. The biological activity of one of the compounds was
      validated in assays monitoring UPEC type 1 pilus biogenesis, type 1 pilus
      dependent biofilm formation and adherence to human bladder epithelial cells. The
      time dependence of the in vivo inhibitory activity and the overall effect of the
      compound on UPEC growth were determined. RESULTS: N-(4-chloro-phenyl)-2-{5-[4
      (pyrrolidine-1-sulfonyl)-phenyl]-[1,3,4]oxadiazol-2-yl sulfanyl}-acetamide (AL1)
      inhibited in vitro pilus subunit polymerization. In bacterial cultures, AL1
      disrupted UPEC type 1 pilus biogenesis and pilus-dependent biofilm formation, and
      resulted in the reduction of bacterial adherence to human bladder epithelial
      cells, without affecting bacterial cell growth. Bacterial exposure to the
      inhibitor led to an almost instantaneous loss of type 1 pili. CONCLUSIONS: We
      have identified and characterized a small molecule that interferes with the
      assembly of type 1 pili. The molecule targets the polymerization step during the
      subunit incorporation cycle of the chaperone-usher pathway. Our discovery
      provides new insight into the design and development of novel anti-virulence
      therapies targeting key virulence factors of bacterial pathogens.

PMID- 24324228
TI  - Postmortem femoral blood concentrations of risperidone.
AB  - Postmortem femoral blood concentrations of the antipsychotic drug risperidone and
      the active metabolite 9-hydroxyrisperidone were determined by an achiral LC-MS/MS
      method in 38 cases. The cause of death was classified as unrelated to risperidone
      in 30 cases, in which the sum of the concentration of the drug and metabolite
      ranged from below the limit of quantification to 0.058 mg/kg (median 0.0098
      mg/kg). This concentration range, which largely corresponds to published in vivo
      plasmalevels under therapy, may serve as a reference for judgment of postmortem
      cases involving risperidone. In one case, risperidone was judged to be a
      contributing factor to death, and the sum of concentrations was 0.29 mg/kg. This
      concentration is of the same order of magnitude as observed for plasma levels in
      clinical intoxication cases. For the remaining seven cases, the cause of death
      was unclear. The measurements observed here do not suggest that risperidone is
      subject to major postmortem redistribution. 

PMID- 24324229
TI  - Codeine to morphine concentration ratios in samples from living subjects and
      autopsy cases after incubation.
AB  - The codeine to morphine concentration ratio is used in forensic toxicology to
      assess if codeine has been ingested alone or if morphine and/or heroin have been
      ingested in addition. In our experience, this interpretation is more difficult in
      autopsy cases compared with samples from living persons, since high morphine
      concentrations are observed in cases where only codeine is assumed to have been
      ingested. We have investigated if codeine and morphine glucuronides are subject
      to cleavage to the same extent in living and autopsy cases in vitro. We included
      whole blood samples from eight living subjects and nine forensic autopsy cases,
      where only codeine ingestion was suspected. All samples were incubated for 2
      weeks at 37 degrees C and analyzed for codeine and six codeine metabolites using
      liquid chromatography tandem mass spectrometry. A reduction in the codeine to
      morphine concentration ratio was found, both in samples from living subjects
      (mean 33%, range 22-50%) and autopsy cases (mean 37%, range 13-54%). The increase
      in the morphine concentrations was greater in the autopsy cases (mean 85%, max
      200%) compared with that of the living cases (mean 51%, max 87%). No changes were
      seen for codeine or codeine-6-glucuronide concentrations. The altered ratios
      might mislead the forensic toxicologist to suspect morphine or heroin consumption
      in cases where only codeine has been ingested. 

PMID- 24324230
TI  - Suicide due to cyclizine overdose.
AB  - Cyclizine is an antihistamine with sedative effect used to treat motion sickness.
      A few studies have reported on cyclizine abuse among teenagers, and cyclizine
      abuse has been reported among opioid dependants receiving methadone, with the
      combination having been reported to produce strong psychoactive effects. Few
      reports exist on the possible toxic effects of cyclizine, and it is regarded as a
      safe drug most often sold as a non-prescription/over-the-counter drug. Very few
      cases of fatalities resulting from cyclizine overdose can be found in the
      literature. We present a case where a 22-year-old female was found unconscious
      and intoxication with drugs and alcohol was suspected. Whole blood from the
      femoral vein, urine and stomach content were collected during autopsy and
      screened for drugs of abuse and medicinal drugs. GC-MS screening of the stomach
      contents revealed presence of cyclizine and meclozine. Cyclizine and meclozine
      concentrations in blood were determined using a UPLC-MS-MS method. Quantification
      of femoral blood revealed a high concentration of cyclizine (16 mg/L), a low
      concentration of meclozine (0.2 mg/L) and ethanol 0.16 g/dL. No other medicinal
      drugs or drugs of abuse were detected. We report on a case of suicide where
      cyclizine was found to be the principal drug and question the safety of this
      drug. 

PMID- 24324220
TI  - Children must be protected from the tobacco industry's marketing tactics.

PMID- 24324231
TI  - Lexical learning and lexical processing in children with developmental language
      impairments.
AB  - Lexical skills are a crucial component of language comprehension and production.
      This paper reviews evidence for lexical-level deficits in children and young
      people with developmental language impairment (LI). Across a range of tasks, LI
      is associated with reduced vocabulary knowledge in terms of both breadth and
      depth and difficulty with learning and retaining new words; evidence is emerging
      from on-line tasks to suggest that low levels of language skill are associated
      with differences in lexical competition in spoken word recognition. The role of
      lexical deficits in understanding the nature of LI is also discussed. 

PMID- 24324232
TI  - What we talk about when we talk about access deficits.
AB  - Semantic impairments have been divided into storage deficits, in which the
      semantic representations themselves are damaged, and access deficits, in which
      the representations are intact but access to them is impaired. The behavioural
      phenomena that have been associated with access deficits include sensitivity to
      cueing, sensitivity to presentation rate, performance inconsistency, negative
      serial position effects, sensitivity to number and strength of competitors,
      semantic blocking effects, disordered selection between strong and weak
      competitors, correlation between semantic deficits and executive function
      deficits and reduced word frequency effects. Four general accounts have been
      proposed for different subsets of these phenomena: abnormal refractoriness, too
      much activation, impaired competitive selection and deficits of semantic control.
      A combination of abnormal refractoriness and impaired competitive selection can
      account for most of the behavioural phenomena, but there remain several open
      questions. In particular, it remains unclear whether access deficits represent a
      single syndrome, a syndrome with multiple subtypes or a variable collection of
      phenomena, whether the underlying deficit is domain-general or domain-specific,
      whether it is owing to disorders of inhibition, activation or selection, and the
      nature of the connection (if any) between access phenomena in aphasia and in
      neurologically intact controls. Computational models offer a promising approach
      to answering these questions. 

PMID- 24324233
TI  - Word production errors in children with developmental language impairments.
AB  - This review focuses on the errors that children with developmental language
      impairments make on three types of word production tasks: lexical retrieval, the
      elicitation of derivationally complex forms and the repetition of non-sense
      forms. The studies discussed in this review come principally from children with
      specific language impairment, and from children who are English-speakers or deaf
      users of British sign language. It is argued that models of word production need
      to be able to account for the data presented here, and need to have explanatory
      power across both modalities (i.e. speech and sign). 

PMID- 24324234
TI  - Theoretical analysis of word production deficits in adult aphasia.
AB  - The cognitive analysis of adult language disorders continues to draw heavily on
      linguistic theory, but increasingly it reflects the influence of connectionist,
      spreading activation models of cognition. In the area of spoken word production,
      'localist' connectionist models represent a natural evolution from the
      psycholingistic theories of earlier decades. By contrast, the parallel
      distributed processing framework forces more radical rethinking of aphasic
      impairments. This paper exemplifies these multiple influences in contemporary
      cognitive aphasiology. Topics include (i) what aphasia reveals about semantic
      phonological interaction in lexical access; (ii) controversies surrounding the
      interpretation of semantic errors and (iii) a computational account of the
      relationship between naming and word repetition in aphasia. Several of these
      topics have been addressed using case series methods, including computational
      simulation of the individual, quantitative error patterns of diverse groups of
      patients and analysis of brain lesions that correlate with error rates and
      patterns. Efforts to map the lesion correlates of nonword errors in naming and
      repetition highlight the involvement of sensorimotor areas in the brain and
      suggest the need to better integrate models of word production with models of
      speech and action. 

PMID- 24324235
TI  - From perceptual to language-mediated categorization.
AB  - From at least two months onwards, infants can form perceptual categories. During
      the first year of life, object knowledge develops from the ability to represent
      individual object features to representing correlations between attributes and to
      integrate information from different sources. At the end of the first year, these
      representations are shaped by labels, opening the way to conceptual knowledge.
      Here, we review the development of object knowledge and object categorization
      over the first year of life. We then present an artificial neural network model
      that models the transition from early perceptual categorization to categories
      mediated by labels. The model informs a current debate on the role of labels in
      object categorization by suggesting that although labels do not act as object
      features they nevertheless affect perceived similarity of perceptually distinct
      objects sharing the same label. The model presents the first step of an
      integrated account from early perceptual categorization to language-based concept
      learning. 

PMID- 24324236
TI  - Neurocognitive insights on conceptual knowledge and its breakdown.
AB  - Conceptual knowledge reflects our multi-modal 'semantic database'. As such, it
      brings meaning to all verbal and non-verbal stimuli, is the foundation for verbal
      and non-verbal expression and provides the basis for computing appropriate
      semantic generalizations. Multiple disciplines (e.g. philosophy, cognitive
      science, cognitive neuroscience and behavioural neurology) have striven to answer
      the questions of how concepts are formed, how they are represented in the brain
      and how they break down differentially in various neurological patient groups. A
      long-standing and prominent hypothesis is that concepts are distilled from our
      multi-modal verbal and non-verbal experience such that sensation in one modality
      (e.g. the smell of an apple) not only activates the intramodality long-term
      knowledge, but also reactivates the relevant intermodality information about that
      item (i.e. all the things you know about and can do with an apple). This multi
      modal view of conceptualization fits with contemporary functional neuroimaging
      studies that observe systematic variation of activation across different modality
      specific association regions dependent on the conceptual category or type of
      information. A second vein of interdisciplinary work argues, however, that even a
      smorgasbord of multi-modal features is insufficient to build coherent,
      generalizable concepts. Instead, an additional process or intermediate
      representation is required. Recent multidisciplinary work, which combines
      neuropsychology, neuroscience and computational models, offers evidence that
      conceptualization follows from a combination of modality-specific sources of
      information plus a transmodal 'hub' representational system that is supported
      primarily by regions within the anterior temporal lobe, bilaterally. 

PMID- 24324237
TI  - Sources of variation in developmental language disorders: evidence from eye
      tracking studies of sentence production.
AB  - Skilled sentence production involves distinct stages of message conceptualization
      (deciding what to talk about) and message formulation (deciding how to talk about
      it). Eye-movement paradigms provide a mechanism for observing how speakers
      accomplish these aspects of production in real time. These methods have recently
      been applied to children with autism spectrum disorder (ASD) and specific
      language impairment (LI) in an effort to reveal qualitative differences between
      groups in sentence production processes. Findings support a multiple-deficit
      account in which language production is influenced not only by lexical and
      syntactic constraints, but also by variation in attention control, inhibition and
      social competence. Thus, children with ASD are especially vulnerable to atypical
      patterns of visual inspection and verbal utterance. The potential to influence
      attentional focus and prime appropriate language structures are considered as a
      mechanism for facilitating language adaptation and learning. 

PMID- 24324238
TI  - The P-chain: relating sentence production and its disorders to comprehension and
      acquisition.
AB  - This article introduces the P-chain, an emerging framework for theory in
      psycholinguistics that unifies research on comprehension, production and
      acquisition. The framework proposes that language processing involves incremental
      prediction, which is carried out by the production system. Prediction necessarily
      leads to prediction error, which drives learning, including both adaptive
      adjustment to the mature language processing system as well as language
      acquisition. To illustrate the P-chain, we review the Dual-path model of sentence
      production, a connectionist model that explains structural priming in production
      and a number of facts about language acquisition. The potential of this and
      related models for explaining acquired and developmental disorders of sentence
      production is discussed. 

PMID- 24324239
TI  - The interface between spoken and written language: developmental disorders.
AB  - We review current knowledge about reading development and the origins of
      difficulties in learning to read. We distinguish between the processes involved
      in learning to decode print, and the processes involved in reading for meaning
      (reading comprehension). At a cognitive level, difficulties in learning to read
      appear to be predominantly caused by deficits in underlying oral language skills.
      The development of decoding skills appears to depend critically upon phonological
      language skills, and variations in phoneme awareness, letter-sound knowledge and
      rapid automatized naming each appear to be causally related to problems in
      learning to read. Reading comprehension difficulties in contrast appear to be
      critically dependent on a range of oral language comprehension skills (including
      vocabulary knowledge and grammatical, morphological and pragmatic skills). 

PMID- 24324240
TI  - Modelling reading development through phonological decoding and self-teaching:
      implications for dyslexia.
AB  - The most influential theory of learning to read is based on the idea that
      children rely on phonological decoding skills to learn novel words. According to
      the self-teaching hypothesis, each successful decoding encounter with an
      unfamiliar word provides an opportunity to acquire word-specific orthographic
      information that is the foundation of skilled word recognition. Therefore,
      phonological decoding acts as a self-teaching mechanism or 'built-in teacher'.
      However, all previous connectionist models have learned the task of reading aloud
      through exposure to a very large corpus of spelling-sound pairs, where an
      'external' teacher supplies the pronunciation of all words that should be learnt.
      Such a supervised training regimen is highly implausible. Here, we implement and
      test the developmentally plausible phonological decoding self-teaching hypothesis
      in the context of the connectionist dual process model. In a series of
      simulations, we provide a proof of concept that this mechanism works. The model
      was able to acquire word-specific orthographic representations for more than 25
      000 words even though it started with only a small number of grapheme-phoneme
      correspondences. We then show how visual and phoneme deficits that are present at
      the outset of reading development can cause dyslexia in the course of reading
      development. 

PMID- 24324242
TI  - Problems with tense marking in children with specific language impairment: not
      how but when.
AB  - Many children with specific language impairment (SLI) have persisting problems in
      the correct use of verb tense, but there has been disagreement as to the
      underlying reason. When we take into account studies using receptive as well as
      expressive language tasks, the data suggest that the difficulty for children with
      SLI is in knowing when to inflect verbs for tense, rather than how to do so. This
      is perhaps not surprising when we consider that tense does not have a transparent
      semantic interpretation, but depends on complex relationships between inflections
      and hierarchically organized clauses. An explanation in terms of syntactic
      limitations contrasts with a popular morpho-phonological account, the Words and
      Rules model. This model, which attributes problems to difficulties with applying
      a rule to generate regular inflected forms, has been widely applied to adult
      acquired disorders. There are striking similarities in the pattern of errors in
      adults with anterior aphasia and children with SLI, suggesting that impairments
      in appreciation of when to mark tense may apply to acquired as well as
      developmental disorders. 

PMID- 24324241
TI  - Connectionist neuropsychology: uncovering ultimate causes of acquired dyslexia.
AB  - Acquired dyslexia offers a unique window on to the nature of the cognitive and
      neural architecture supporting skilled reading. This paper provides an
      integrative overview of recent empirical and computational work on acquired
      dyslexia within the context of the primary systems framework as implemented in
      connectionist neuropsychological models. This view proposes that damage to
      general visual, phonological or semantic processing abilities are the root causes
      of different forms of acquired dyslexia. Recent case-series behavioural evidence
      concerning pure alexia, phonological dyslexia and surface dyslexia that supports
      this perspective is presented. Lesion simulations of these findings within
      connectionist models of reading demonstrate the viability of this approach. The
      commitment of such models to learnt representations allows them to capture key
      aspects of performance in each type of acquired dyslexia, particularly the
      associated non-reading deficits, the role of relearning and the influence of
      individual differences in the premorbid state of the reading system.
      Identification of these factors not only advances our understanding of acquired
      dyslexia and the mechanisms of normal reading but they are also relevant to the
      complex interactions underpinning developmental reading disorders. 

PMID- 24324243
TI  - Patients with impaired verb-tense processing: do they know that yesterday is
      past?
AB  - This paper begins with a focus on the task of stem inflection, where participants
      are given a verb stem and asked to produce the verb's past-tense form, which can
      produce a neuropsychological double dissociation with respect to regular versus
      irregular verbs. Two differing theoretical interpretations are outlined: one is
      based on specifically morphological and separate brain mechanisms for processing
      regular versus irregular verbs; the other argues that the two sides of the
      dissociation can arise from one procedure, which is not specifically
      morphological, and which relies to differing extents on phonological versus
      semantic information for regular versus irregular verbs. We then present data
      from a different version of the task, in which patients were given past-tense
      forms and asked to produce the present-tense or stem forms (talked -> talk and
      ate -> eat). This change yielded a very different pattern of performance in four
      non-fluent aphasic patients as a function of the regular-irregular manipulation,
      an outcome which is argued to be more compatible with the single- than the dual
      mechanism account. Finally, we present a small amount of data from a task in
      which the patient was asked to judge whether spoken regular and irregular verb
      stems and past-tense forms indicated actions occurring today or yesterday. This
      task produced an even more different and intriguing pattern of performance
      suggesting a deficit in morpho-syntactic knowledge: not how to produce past-tense
      forms but what such forms mean and how that understanding interacts with verb
      regularity. The paper concludes with a discussion of how the research field of
      acquired disorders of tense processing might advance as a result of new
      approaches, in particular those informed by studies of developmental disorders. 

PMID- 24324244
TI  - When words fail us: insights into language processing from developmental and
      acquired disorders.
AB  - Acquired disorders of language represent loss of previously acquired skills,
      usually with relatively specific impairments. In children with developmental
      disorders of language, we may also see selective impairment in some skills; but
      in this case, the acquisition of language or literacy is affected from the
      outset. Because systems for processing spoken and written language change as they
      develop, we should beware of drawing too close a parallel between developmental
      and acquired disorders. Nevertheless, comparisons between the two may yield new
      insights. A key feature of connectionist models simulating acquired disorders is
      the interaction of components of language processing with each other and with
      other cognitive domains. This kind of model might help make sense of patterns of
      comorbidity in developmental disorders. Meanwhile, the study of developmental
      disorders emphasizes learning and change in underlying representations, allowing
      us to study how heterogeneity in cognitive profile may relate not just to
      neurobiology but also to experience. Children with persistent language
      difficulties pose challenges both to our efforts at intervention and to theories
      of learning of written and spoken language. Future attention to learning in
      individuals with developmental and acquired disorders could be of both
      theoretical and applied value. 

PMID- 24324246
TI  - Developmental disorders: what can be learned from cognitive neuropsychology?
AB  - The discipline of cognitive neuropsychology has been important for informing
      theories of cognition and describing the nature of acquired cognitive disorders,
      but its applicability in a developmental context has been questioned. Here, we
      revisit this issue, asking whether the cognitive neuropsychological approach can
      be helpful for exploring the nature and causes of developmental disorders and, if
      so, how. We outline the key features of the cognitive neuropsychological
      approach, and then consider how some of the major challenges to this approach
      from a developmental perspective might be met. In doing so, we distinguish
      between challenges to the methods of cognitive neuropsychology and those facing
      its deeper conceptual underpinnings. We conclude that the detailed investigation
      of patterns of both associations and dissociations, and across both developmental
      and acquired cases, can assist in describing the cognitive deficits within
      developmental disorders and in delineating possible causal pathways to their
      acquisition. 

PMID- 24324247
TI  - Preface. Language in developmental and acquired disorders.

PMID- 24324245
TI  - From temporal processing to developmental language disorders: mind the gap.
AB  - The 'rapid temporal processing' and the 'temporal sampling framework' hypotheses
      have been proposed to account for the deficits in language and literacy
      development seen in specific language impairment and dyslexia. This paper reviews
      these hypotheses and concludes that the proposed causal chains between the
      presumed auditory processing deficits and the observed behavioural manifestation
      of the disorders are vague and not well established empirically. Several problems
      and limitations are identified. Most data concern correlations between distantly
      related tasks, and there is considerable heterogeneity and variability in
      performance as well as concerns about reliability and validity. Little attention
      is paid to the distinction between ostensibly perceptual and metalinguistic tasks
      or between implicit and explicit modes of performance, yet measures are assumed
      to be pure indicators of underlying processes or representations. The possibility
      that diagnostic categories do not refer to causally and behaviourally homogeneous
      groups needs to be taken seriously, taking into account genetic and
      neurodevelopmental studies to construct multiple-risk models. To make progress in
      the field, cognitive models of each task must be specified, including performance
      domains that are predicted to be deficient versus intact, testing multiple
      indicators of latent constructs and demonstrating construct reliability and
      validity. 

PMID- 24324248
TI  - Evaluation of a personal and environmental dosemeter based on CR-39 track
      detectors in quasi-monoenergetic neutron fields.
AB  - In this paper, the evaluation of the dosimetric capability of a detector based on
      a CR-39 solid-state nuclear track detector coupled to a 1 cm thickness of PMMA
      radiator was made with the aim of understanding the applicability of this
      technique to personal and environmental neutron dosimetry. The dosemeter has been
      exposed to monoenergetic and quasi-monoenergetic neutron beams at PTB in
      Braunschweig, Germany and at Ithemba Laboratories, in Faure, South Africa, with
      peak energies ranging from 0.565 to 100 MeV. The results showed a response that
      is almost independent of the neutron energy in the whole energy range. 

PMID- 24324249
TI  - Significant change in the construction of a door to a room with slowed down
      neutron field by means of commonly used inexpensive protective materials.
AB  - The detailed analysis of nuclear reactions occurring in materials of the door is
      presented for the typical construction of an entrance door to a room with a
      slowed down neutron field. The changes in the construction of the door were
      determined to reduce effectively the level of neutron and gamma radiation in the
      vicinity of the door in a room adjoining the neutron field room. Optimisation of
      the door construction was performed with the use of Monte Carlo calculations
      (GEANT4). The construction proposed in this paper bases on the commonly used
      inexpensive protective materials such as borax (13.4 cm), lead (4 cm) and
      stainless steel (0.1 and 0.5 cm on the side of the neutron field room and of the
      adjoining room, respectively). The improved construction of the door, worked out
      in the presented studies, can be an effective protection against neutrons with
      energies up to 1 MeV. 

PMID- 24324250
TI  - A micro-gap, air-filled ionisation chamber as a detector for criticality accident
      dosimetry.
AB  - A micro-gap air-filled ionisation chamber was designed for criticality dosimetry.
      The special feature of the chamber is its very small gap between electrodes of
      only 0.3 mm. This prevents ion recombination at high dose rates and minimises the
      influence of gas on secondary particles spectrum. The electrodes are made of
      polypropylene because of higher content of hydrogen in this material, when
      compared with soft tissue. The difference between neutron and gamma sensitivity
      in such chamber becomes practically negligible. The chamber's envelope contains
      two specially connected capacitors, one for polarising the electrodes and the
      other for collecting the ionisation charge. 

PMID- 24324251
TI  - Radon decay products in realistic living rooms and their activity distributions
      in human respiratory system.
AB  - In this study, the individual activity concentrations of attached short-lived
      radon decay products ((218)Po, (214)Pb and (214)Po) in aerosol particles were
      measured in ten poorly ventilated realistic living rooms. Using standard
      methodologies, the samples were collected using a filter holder technique
      connected with alpha-spectrometric. The mean value of air activity concentration
      of these radionuclides was found to be 5.3+/-0.8, 4.5+/-0.5 and 3.9+/-0.4 Bq m(
      3), respectively. Based on the physical properties of the attached decay products
      and physiological parameters of light work activity for an adult human male
      recommended by ICRP 66 and considering the parameters of activity size
      distribution (AMD = 0.25 MUm and sigma(g) = 2.5) given by NRC, the total and
      regional deposition fractions in each airway generation could be evaluated.
      Moreover, the total and regional equivalent doses in the human respiratory tract
      could be estimated. In addition, the surface activity distribution per generation
      is calculated for the bronchial region (BB) and the bronchiolar region (bb) of
      the respiratory system. The maximum values of these activities were found in the
      upper bronchial airway generations.

PMID- 24324252
TI  - Radiofrequency contact currents: sensory responses and dosimetry.
AB  - The process of setting science-based exposure standards (or guidelines) for
      radiofrequency (RF) contact current exposure has been disadvantaged by a lack of
      relevant data. The authors first review the essential features and results of the
      available studies and illustrate the apparent discrepancies among them. Then,
      they examine the manner in which current was administered in these studies and
      suggest as to how the physical relationship of a contacting finger to the current
      electrode may play a role in affecting sensory thresholds specific to those
      configurations. A major factor in this analysis relates to whether current
      density is uniformly distributed across the contact area or whether an
      electrode's 'edge effects' enhance currents with a net effect of decreasing
      apparent thresholds, when expressed as the bulk current entering a subject. For
      an exposure with a clear hazard potential, thresholds of human sensory response
      to RF currents require further investigation. 

PMID- 24324253
TI  - Neutron detection by a CR-39 detector and analysis of proton tracks etched in the
      same and opposite directions.
AB  - A program code to simulate neutron interactions with a CR-39 detector and
      calculate parameters describing the induced etched proton tracks in the CR-39
      material was previously developed(( 1)). This code was used to understand the
      mechanisms involved during interactions with neutrons in the CR-39 material and
      the influence of the etching process, enabling an improvement in the efficiency
      of the CR-39 detector. Due to neutron interaction with atoms of the detector
      material, the created protons are emitted in different directions and their
      latent tracks are oriented randomly within the detector. The aim of this paper is
      to show differences between the number of visible tracks etched in the same and
      opposite directions from both sides of the detector. The efficiency of neutron
      detection was analysed as a function of the removed layer and neutron energy for
      both sides of detector. 

PMID- 24324254
TI  - Proton-impact ionisation cross sections for nanodosimetric track structure
      simulations.
AB  - Monte Carlo simulations of the particle track structure require accurate ion- and
      electron-impact cross-section data of the medium. These data are scarce and often
      inconsistent when measured by different groups. In this work, literature data on
      ionisation cross sections (CSs) of nitrogen and propane for protons with energies
      0.1-10 MeV are reviewed and implemented in the code PTra. Methane data were used
      to obtain proton-impact CSs of propane due to their absence in the literature.
      PTra is benchmarked by comparing simulated particle-track parameters to
      experimental results, measured with an ion-counting nanodosemeter. 

PMID- 24324255
TI  - Constitutive and nitrogen catabolite repression-sensitive production of Gat1
      isoforms.
AB  - Nitrogen catabolite repression (NCR)-sensitive transcription is activated by Gln3
      and Gat1. In nitrogen excess, Gln3 and Gat1 are cytoplasmic, and transcription is
      minimal. In poor nitrogen, Gln3 and Gat1 become nuclear and activate
      transcription. A long standing paradox has surrounded Gat1 production. Gat1 was
      first reported as an NCR-regulated activity mediating NCR-sensitive transcription
      in gln3 deletion strains. Upon cloning, GAT1 transcription was, as predicted, NCR
      sensitive and Gln3- and Gat1-activated. In contrast, Western blots of Gat1
      Myc(13) exhibited two constitutively produced species. Investigating this
      paradox, we demonstrate that wild type Gat1 isoforms (IsoA and IsoB) are
      initiated at Gat1 methionines 40, 95, and/or 102, but not at methionine 1. Their
      low level production is the same in rich and poor nitrogen conditions. When the
      Myc(13) tag is placed after Gat1 Ser-233, four N-terminal Gat1 isoforms (IsoC-F)
      are also initiated at methionines 40, 95, and/or 102. However, their production
      is highly NCR-sensitive, being greater in proline than glutamine medium.
      Surprisingly, all Gat1 isoforms produced in sufficient quantities to be
      confidently analyzed (IsoA, IsoC, and IsoD) require Gln3 and UASGATA promoter
      elements, both requirements typical of NCR-sensitive transcription. These data
      demonstrate that regulated Gat1 production is more complex than previously
      recognized, with wild type versus truncated Gat1 proteins failing to be regulated
      in parallel. This is the first reported instance of Gln3 UASGATA-dependent
      protein production failing to derepress in nitrogen poor conditions. A Gat1-lacZ
      ORF swap experiment indicated sequence(s) responsible for the nonparallel
      production are downstream of Gat1 leucine 61. 

PMID- 24324256
TI  - Role of the LEXE motif of protein-primed DNA polymerases in the interaction with
      the incoming nucleotide.
AB  - The LEXE motif, conserved in eukaryotic type DNA polymerases, is placed close to
      the polymerization active site. Previous studies suggested that the second Glu
      was involved in binding a third noncatalytic ion in bacteriophage RB69 DNA
      polymerase. In the protein-primed DNA polymerase subgroup, the LEXE motif lacks
      the first Glu in most cases, but it has a conserved Phe/Trp and a Gly preceding
      that position. To ascertain the role of those residues, we have analyzed the
      behavior of mutants at the corresponding phi29 DNA polymerase residues Gly-481,
      Trp-483, Ala-484, and Glu-486. We show that mutations at Gly-481 and Trp-483
      hamper insertion of the incoming dNTP in the presence of Mg(2+) ions, a reaction
      highly improved when Mn(2+) was used as metal activator. These results, together
      with previous crystallographic resolution of phi29 DNA polymerase ternary
      complex, allow us to infer that Gly-481 and Trp-483 could form a pocket that
      orients Val-250 to interact with the dNTP. Mutants at Glu-486 are also defective
      in polymerization and, as mutants at Gly-481 and Trp-483, in the
      pyrophosphorolytic activity with Mg(2+). Recovery of both reactions with Mn(2+)
      supports a role for Glu-486 in the interaction with the pyrophosphate moiety of
      the dNTP. 

PMID- 24324257
TI  - Unfolded protein response signaling and metabolic diseases.
AB  - The endoplasmic reticulum (ER) is a central organelle for protein biosynthesis,
      folding, and traffic. Perturbations in ER homeostasis create a condition termed
      ER stress and lead to activation of the complex signaling cascade called the
      unfolded protein response (UPR). Recent studies have documented that the UPR
      coordinates multiple signaling pathways and controls various physiologies in
      cells and the whole organism. Furthermore, unresolved ER stress has been
      implicated in a variety of metabolic disorders, such as obesity and type 2
      diabetes. Therefore, intervening in ER stress and modulating signaling components
      of the UPR would provide promising therapeutics for the treatment of human
      metabolic diseases. 

PMID- 24324258
TI  - C-type lectin binds to beta-integrin to promote hemocytic phagocytosis in an
      invertebrate.
AB  - Phagocytosis is a conserved cellular response among metazoans. Opsonins are some
      molecules that label targets to increase their susceptibility to phagocytosis.
      Opsonins are usually captured by receptors on the surface of phagocytes. Our
      previous study found the C-type lectin FcLec4 from Chinese white shrimp
      Fenneropenaeus chinensis might function as an opsonin to facilitate bacterial
      clearance. In the present study we purified the native FcLec4 protein and
      confirmed its opsonic activity in the near relation, kuruma shrimp Marsupenaeus
      japonicus. The possible receptor of FcLec4 was identified as beta-integrin by
      panning a T7 phage display library of shrimp hemocytes and then confirmed by co
      immunoprecipitation assay. We further proved that the interaction between FcLec4
      and beta-integrin did not rely on the carbohydrate recognition domain but on the
      N terminus of FcLec4. In addition, inhibition of FcLec4 expression using RNAi
      delayed bacterial clearance, and beta-integrin knockdown suppressed the opsonic
      activity of FcLec4. This study is the first to show the direct interaction
      between an opsonin and its receptor in crustaceans. Our study provides new
      insights into invertebrate phagocytosis and the functions of C-type lectins. 

PMID- 24324259
TI  - CYP82Y1 is N-methylcanadine 1-hydroxylase, a key noscapine biosynthetic enzyme in
      opium poppy.
AB  - Noscapine is a phthalideisoquinoline alkaloid investigated for its potent
      pharmacological properties. Although structurally elucidated more than a century
      ago, the biosynthesis of noscapine has not been established. Radiotracer studies
      have shown that noscapine is derived from the protoberberine alkaloid (S)
      scoulerine and has been proposed to proceed through (S)-N-methylcanadine.
      However, pathway intermediates involved in the conversion of N-methylcanadine to
      noscapine have not been identified. We report the isolation and characterization
      of the cytochrome P-450 CYP82Y1, which catalyzes the 1-hydroxylation of N
      methylcanadine to 1-hydroxy-N-methylcanadine. Comparison of transcript and
      metabolite profiles of eight opium poppy chemotypes revealed four cytochrome P
      450s, three from the CYP82 and one from the CYP719 families, that were tightly
      correlated with noscapine accumulation. Recombinant CYP82Y1 was the only enzyme
      that accepted (R,S)-N-methylcanadine as a substrate with strict specificity and
      high affinity. As expected, CYP82Y1 was abundantly expressed in opium poppy stems
      where noscapine accumulation is highest among plant organs. Suppression of
      CYP82Y1 using virus-induced gene silencing caused a significant reduction in the
      levels of noscapine, narcotoline, and a putative downstream secoberbine
      intermediate and also resulted in increased accumulation of the upstream pathway
      intermediates scoulerine, tetrahydrocolum-bamine, canadine, and N-methylcanadine.
      The combined biochemical and physiological data support the 1-hydroxylation of
      (S)-N-methylcanadine catalyzed by CYP82Y1 as the first committed step in the
      formation of noscapine in opium poppy. 

PMID- 24324260
TI  - Overexpression of c-Met and CD44v6 receptors contributes to autocrine TGF-beta1
      signaling in interstitial lung disease.
AB  - The hepatocyte growth factor (HGF) and the HGF receptor Met pathway are important
      in the pathogenesis of interstitial lung disease (ILD). Alternatively spliced
      isoforms of CD44 containing variable exon 6 (CD44v6) and its ligand hyaluronan
      (HA) alter cellular function in response to interaction between CD44v6 and HGF.
      TGF-beta1 is the crucial cytokine that induces fibrotic action in ILD fibroblasts
      (ILDFbs). We have identified an autocrine TGF-beta1 signaling that up-regulates
      both Met and CD44v6 mRNA and protein expression. Western blot analysis, flow
      cytometry, and immunostaining revealed that CD44v6 and Met colocalize in
      fibroblasts and in tissue sections from ILD patients and in lungs of bleomycin
      treated mice. Interestingly, cell proliferation induced by TGF-beta1 is mediated
      through Met and CD44v6. Further, cell proliferation mediated by TGF-beta1/CD44v6
      is ERK-dependent. In contrast, action of Met on ILDFb proliferation does not
      require ERK but does require p38(MAPK). ILDFbs were sorted into CD44v6(+)/Met(+)
      and CD44v6(-)/Met(+) subpopulations. HGF inhibited TGF-beta1-stimulated collagen
      1 and alpha-smooth muscle cell actin expression in both of these subpopulations
      by interfering with TGF-beta1 signaling. HGF alone markedly stimulated CD44v6
      expression, which in turn regulated collagen-1 synthesis. Our data with primary
      lung fibroblast cultures with respect to collagen-1, CD44v6, and Met expressions
      were supported by immunostaining of lung sections from bleomycin-treated mice and
      from ILD patients. These results define the relationships between CD44v6, Met,
      and autocrine TGF-beta1 signaling and the potential modulating influence of HGF
      on TGF-beta1-induced CD44v6-dependent fibroblast function in ILD fibrosis. 

PMID- 24324261
TI  - The Hippo pathway effectors TAZ/YAP regulate dicer expression and microRNA
      biogenesis through Let-7.
AB  - MicroRNAs (miRNAs) are genome-encoded small double-stranded RNAs that have
      emerged as key regulators of gene expression and are implicated in most aspects
      of human development and disease. Canonical miRNA biogenesis involves processing
      of ~70-nucleotide pre-miRNA hairpins by Dicer to generate mature ~22-nucleotide
      miRNAs, which target complementary RNA sequences. Despite the importance of miRNA
      biogenesis, signaling mechanisms controlling this process are poorly defined.
      Here we demonstrate that the post-transcriptional regulation of Dicer is
      controlled by the cell density-mediated localization of the Hippo pathway
      effectors TAZ (transcriptional co-activator with PDZ-binding motif) and YAP (Yes
      associated protein) (TAZ/YAP). We show that nuclear TAZ/YAP, which are abundant
      at low cell density, are required for efficient pre-miRNA processing. Knockdown
      of TAZ/YAP in low density cells, or density-mediated sequestration of TAZ/YAP
      into the cytoplasm, results in the defective processing of pre-miRNAs.
      Strikingly, one exception is Let-7, which accumulates upon loss of nuclear
      TAZ/YAP, leading to Let-7-dependent reduction in Dicer levels. Accordingly,
      inhibition of Let-7 rescues the miRNA biogenesis defects observed following
      TAZ/YAP knockdown. Thus, density-regulated TAZ/YAP localization defines a
      critical and previously unrecognized mechanism by which cells relay cell contact
      induced cues to control miRNA biogenesis. 

PMID- 24324262
TI  - Ubiquitin-interacting motifs confer full catalytic activity, but not ubiquitin
      chain substrate specificity, to deubiquitinating enzyme USP37.
AB  - Ubiquitin-specific proteases (USPs) consist of a family of deubiquitinating
      enzymes with more than 50 members in humans. Three of them, including USP37,
      contain ubiquitin-interacting motifs (UIMs), an ~20-amino acid alpha-helical
      stretch that binds to ubiquitin. However, the roles of the UIMs in these USP
      enzymes remain unknown. USP37 has three UIMs, designated here as UIMs 1, 2, and 3
      from the N-terminal side, between the Cys and His boxes comprising the catalytic
      core. Here, we examined the role of the UIMs in USP37 using its mutants that
      harbor mutations in the UIMs. The nuclear localization of USP37 was not affected
      by the UIM mutations. However, mutations in UIM2 or UIM3, but not UIM1, resulted
      in a significant decrease in USP37 binding to ubiquitinated proteins in the cell.
      In vitro, a region of USP37 harboring the three UIMs also bound to both Lys(48)
      linked and Lys(63)-linked ubiquitin chains in a UIM2- and UIM3-dependent manner.
      The level of USP37 ubiquitination was also reduced by mutations in UIM2 or UIM3,
      suggesting their role in ubiquitination of USP37 itself. Finally, mutants lacking
      functional UIM2 or UIM3 exhibited a reduced isopeptidase activity toward
      ubiquitinated proteins in the cell and both Lys(48)-linked and Lys(63)-linked
      ubiquitin chains. These results suggested that the UIMs in USP37 contribute to
      the full enzymatic activity, but not ubiquitin chain substrate specificity, of
      USP37 possibly by holding the ubiquitin chain substrate in the proximity of the
      catalytic core. 

PMID- 24324263
TI  - Down-regulation of mortalin exacerbates Abeta-mediated mitochondrial
      fragmentation and dysfunction.
AB  - Mitochondrial dynamics greatly influence the biogenesis and morphology of
      mitochondria. Mitochondria are particularly important in neurons, which have a
      high demand for energy. Therefore, mitochondrial dysfunction is strongly
      associated with neurodegenerative diseases. Until now various post-translational
      modifications for mitochondrial dynamic proteins and several regulatory proteins
      have explained complex mitochondrial dynamics. However, the precise mechanism
      that coordinates these complex processes remains unclear. To further understand
      the regulatory machinery of mitochondrial dynamics, we screened a mitochondrial
      siRNA library and identified mortalin as a potential regulatory protein. Both
      genetic and chemical inhibition of mortalin strongly induced mitochondrial
      fragmentation and synergistically increased Abeta-mediated cytotoxicity as well
      as mitochondrial dysfunction. Importantly we determined that the expression of
      mortalin in Alzheimer disease (AD) patients and in the triple transgenic-AD mouse
      model was considerably decreased. In contrast, overexpression of mortalin
      significantly suppressed Abeta-mediated mitochondrial fragmentation and cell
      death. Taken together, our results suggest that down-regulation of mortalin may
      potentiate Abeta-mediated mitochondrial fragmentation and dysfunction in AD. 

PMID- 24324264
TI  - Cognitive deficits and disruption of neurogenesis in a mouse model of
      apolipoprotein E4 domain interaction.
AB  - Apolipoprotein E4 (apoE4) allele is the major genetic risk factor for sporadic
      Alzheimer disease (AD) due to the higher prevalence and earlier onset of AD in
      apoE4 carriers. Accumulating data suggest that the interaction between the N- and
      the C-terminal domains in the protein may be the main pathologic feature of
      apoE4. To test this hypothesis, we used Arg-61 mice, a model of apoE4 domain
      interaction, by introducing the domain interaction feature of human apoE4 into
      native mouse apoE. We carried out hippocampus-dependent learning and memory tests
      and related cellular and molecular assays on 12- and 3-month-old Arg-61 and age
      matched background C57BL/6J mice. Learning and memory task performance were
      impaired in Arg-61 mice at both old and young ages compared with C57BL/6J mice.
      Surprisingly, young Arg-61 mice had more mitotic doublecortin-positive cells in
      the subgranular zone; mRNA levels of brain-derived neurotrophic factor (BDNF) and
      TrkB were also higher in 3-month-old Arg-61 hippocampus compared with C57BL/6J
      mice. These early-age neurotrophic and neurogenic (proliferative) effects in the
      Arg-61 mouse may be an inadequate compensatory but eventually detrimental attempt
      by the system to "repair" itself. This is supported by the higher cleaved caspase
      3 levels in the young animals that not only persisted, but increased in old age,
      and the lower levels of doublecortin at old age in the hippocampus of Arg-61
      mice. These results are consistent with human apoE4-dependent cognitive and neuro
      pathologic changes, supporting the principal role of domain interaction in the
      pathologic effect of apoE4. Domain interaction is, therefore, a viable
      therapeutic/prophylactic target for cognitive impairment and AD in apoE4
      subjects. 

PMID- 24324265
TI  - A C4-oxidizing lytic polysaccharide monooxygenase cleaving both cellulose and
      cello-oligosaccharides.
AB  - Lignocellulosic biomass is a renewable resource that significantly can substitute
      fossil resources for the production of fuels, chemicals, and materials. Efficient
      saccharification of this biomass to fermentable sugars will be a key technology
      in future biorefineries. Traditionally, saccharification was thought to be
      accomplished by mixtures of hydrolytic enzymes. However, recently it has been
      shown that lytic polysaccharide monooxygenases (LPMOs) contribute to this process
      by catalyzing oxidative cleavage of insoluble polysaccharides utilizing a
      mechanism involving molecular oxygen and an electron donor. These enzymes thus
      represent novel tools for the saccharification of plant biomass. Most
      characterized LPMOs, including all reported bacterial LPMOs, form aldonic acids,
      i.e., products oxidized in the C1 position of the terminal sugar. Oxidation at
      other positions has been observed, and there has been some debate concerning the
      nature of this position (C4 or C6). In this study, we have characterized an LPMO
      from Neurospora crassa (NcLPMO9C; also known as NCU02916 and NcGH61-3).
      Remarkably, and in contrast to all previously characterized LPMOs, which are
      active only on polysaccharides, NcLPMO9C is able to cleave soluble cello
      oligosaccharides as short as a tetramer, a property that allowed detailed product
      analysis. Using mass spectrometry and NMR, we show that the cello-oligosaccharide
      products released by this enzyme contain a C4 gemdiol/keto group at the
      nonreducing end. 

PMID- 24324266
TI  - First evidence for a covalent linkage between enterobacterial common antigen and
      lipopolysaccharide in Shigella sonnei phase II ECALPS.
AB  - Enterobacterial common antigen (ECA) is expressed by Gram-negative bacteria
      belonging to Enterobacteriaceae, including emerging drug-resistant pathogens such
      as Escherichia coli, Klebsiella pneumoniae, and Proteus spp. Recent studies have
      indicated the importance of ECA for cell envelope integrity, flagellum
      expression, and resistance of enteric bacteria to acetic acid and bile salts.
      ECA, a heteropolysaccharide built from the trisaccharide repeating unit, ->3)
      alpha-D-Fucp4NAc-(1->4)-beta-D-ManpNAcA-(1->4)-alpha-D-GlcpNAc-(1->, occurs as a
      cyclic form (ECA(CYC)), a phosphatidylglycerol (PG)-linked form (ECA(PG)), and an
      endotoxin/lipopolysaccharide (LPS)-associated form (ECA(LPS)). Since the
      discovery of ECA in 1962, the structures of ECA(PG) and ECA(CYC) have been
      completely elucidated. However, no direct evidence has been presented to support
      a covalent linkage between ECA and LPS; only serological indications of co
      association have been reported. This is paradoxical, given that ECA was first
      identified based on the capacity of immunogenic ECA(LPS) to elicit antibodies
      cross-reactive with enterobacteria. Using a simple isolation protocol supported
      by serological tracking of ECA epitopes and NMR spectroscopy and mass
      spectrometry, we have succeeded in the first detection, isolation, and complete
      structural analysis of poly- and oligosaccharides of Shigella sonnei phase II
      ECA(LPS). ECA(LPS) consists of the core oligosaccharide substituted with one to
      four repeating units of ECA at the position occupied by the O-antigen in the case
      of smooth S. sonnei phase I. These data represent the first structural evidence
      for the existence of ECA(LPS) in the half-century since it was first discovered
      and provide insights that could prove helpful in further structural analyses and
      screening of ECA(LPS) among Enterobacteriaceae species.

PMID- 24324267
TI  - Zinc finger protein 451 is a novel Smad corepressor in transforming growth factor
      beta signaling.
AB  - ZNF451 is a transcriptional cofactor localized to promyelocytic leukemia bodies.
      Here, we present evidence demonstrating that ZNF451 physically interacts with
      Smad3/4 and functionally inhibits TGF-beta signaling. Increased expression of
      ZNF451 attenuates TGF-beta-induced growth inhibitory and gene transcriptional
      responses, whereas depletion of ZNF451 enhances TGF-beta responses.
      Mechanistically, ZNF451 blocks the ability of Smad3/4 to recruit p300 in response
      to TGF-beta, which causes reduction of histone H3K9 acetylation on the promoters
      of TGF-beta target genes. Taken together, ZNF451 acts as a transcriptional
      corepressor for Smad3/4 and negatively regulates TGF-beta signaling. 

PMID- 24324268
TI  - Collapsin response mediator protein 5 (CRMP5) induces mitophagy, thereby
      regulating mitochondrion numbers in dendrites.
AB  - Degradation of damaged mitochondria by mitophagy is an essential process to
      ensure cell homeostasis. Because neurons, which have a high energy demand, are
      particularly dependent on the mitochondrial dynamics, mitophagy represents a key
      mechanism to ensure correct neuronal function. Collapsin response mediator
      proteins 5 (CRMP5) belongs to a family of cytosolic proteins involved in axon
      guidance and neurite outgrowth signaling during neural development. CRMP5, which
      is highly expressed during brain development, plays an important role in the
      regulation of neuronal polarity by inhibiting dendrite outgrowth at early
      developmental stages. Here, we demonstrated that CRMP5 was present in vivo in
      brain mitochondria and is targeted to the inner mitochondrial membrane. The
      mitochondrial localization of CRMP5 induced mitophagy. CRMP5 overexpression
      triggered a drastic change in mitochondrial morphology, increased the number of
      lysosomes and double membrane vesicles termed autophagosomes, and enhanced the
      occurrence of microtubule-associated protein 1 light chain 3 (LC3) at the
      mitochondrial level. Moreover, the lipidated form of LC3, LC3-II, which triggers
      autophagy by insertion into autophagosomes, enhanced mitophagy initiation.
      Lysosomal marker translocates at the mitochondrial level, suggesting
      autophagosome-lysosome fusion, and induced the reduction of mitochondrial content
      via lysosomal degradation. We show that during early developmental stages the
      strong expression of endogenous CRMP5, which inhibits dendrite growth, correlated
      with a decrease of mitochondrial content. In contrast, the knockdown or a
      decrease of CRMP5 expression at later stages enhanced mitochondrion numbers in
      cultured neurons, suggesting that CRMP5 modulated these numbers. Our study
      elucidates a novel regulatory mechanism that utilizes CRMP5-induced mitophagy to
      orchestrate proper dendrite outgrowth and neuronal function. 

PMID- 24324269
TI  - Sorting of beta1-adrenergic receptors is mediated by pathways that are either
      dependent on or independent of type I PDZ, protein kinase A (PKA), and SAP97.
AB  - The beta1-adrenergic receptor (beta1-AR) is a target for treatment of major
      cardiovascular diseases, such as heart failure and hypertension. Recycling of
      agonist-internalized beta1-AR is dependent on type I PSD-95/DLG/ZO1 (PDZ) in the
      C-tail of the beta1-AR and on protein kinase A (PKA) activity (Gardner, L. A.,
      Naren, A. P., and Bahouth, S. W. (2007) J. Biol. Chem. 282, 5085-5099). We
      explored the effects of point mutations in the PDZ and in the activity of PKA on
      recycling of the beta1-AR and its binding to the PDZ-binding protein SAP97. These
      studies indicated that beta1-AR recycling was inhibited by PKA inhibitors and by
      mutations in the PDZ that interfered with SAP97 binding. The trafficking effects
      of short sequences differing in PDZ and SAP97 binding were examined using
      chimeric mutant beta1-AR. beta1-AR chimera containing the type I PDZ of the beta2
      adrenergic receptor that does not bind to SAP97 failed to recycle except when
      serine 312 was mutated to aspartic acid. beta1-AR chimera with type I PDZ
      sequences from the C-tails of aquaporin-2 or GluR1 recycled in a SAP97- and PKA
      dependent manner. Non-PDZ beta1-AR chimera derived from MU-opioid, dopamine 1, or
      GluR2 receptors promoted rapid recycling of chimeric beta1-AR in a SAP97- and PKA
      independent manner. Moreover, the nature of the residue at position -3 in the PDZ
      regulated whether the beta1-AR was internalized alone or in complex with SAP97.
      These results indicate that divergent pathways were involved in trafficking the
      beta1-AR and provide a roadmap for its trafficking via type I PDZs versus non
      PDZs. 

PMID- 24324270
TI  - Rhes, a striatal-selective protein implicated in Huntington disease, binds beclin
      1 and activates autophagy.
AB  - The protein mutated in Huntington disease (HD), mutant huntingtin (mHtt), is
      expressed throughout the brain and body. However, the pathology of HD is
      characterized by early and dramatic destruction selectively of the striatum. We
      previously reported that the striatal-specific protein Rhes binds mHtt and
      enhances its cytotoxicity. Moreover, Rhes-deleted mice are dramatically protected
      from neurodegeneration and motor dysfunction in mouse models of HD. We now report
      a function of Rhes in autophagy, a lysosomal degradation pathway implicated in
      aging and HD neurodegeneration. In PC12 cells, deletion of endogenous Rhes
      decreases autophagy, whereas Rhes overexpression activates autophagy. These
      effects are independent of mTOR and opposite in the direction predicted by the
      known activation of mTOR by Rhes. Rhes robustly binds the autophagy regulator
      Beclin-1, decreasing its inhibitory interaction with Bcl-2 independent of JNK-1
      signaling. Finally, co-expression of mHtt blocks Rhes-induced autophagy
      activation. Thus, the isolated pathology and delayed onset of HD may reflect the
      striatal-selective expression and changes in autophagic activity of Rhes. 

PMID- 24324271
TI  - Mineralogy of a mudstone at Yellowknife Bay, Gale crater, Mars.
AB  - Sedimentary rocks at Yellowknife Bay (Gale crater) on Mars include mudstone
      sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain
      detrital basaltic minerals, calcium sulfates, iron oxide or hydroxides, iron
      sulfides, amorphous material, and trioctahedral smectites. The John Klein
      smectite has basal spacing of ~10 angstroms, indicating little interlayer
      hydration. The Cumberland smectite has basal spacing at both ~13.2 and ~10
      angstroms. The larger spacing suggests a partially chloritized interlayer or
      interlayer magnesium or calcium facilitating H2O retention. Basaltic minerals in
      the mudstone are similar to those in nearby eolian deposits. However, the
      mudstone has far less Fe-forsterite, possibly lost with formation of smectite
      plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay
      mineral formation on Mars extended beyond Noachian time. 

PMID- 24324278
TI  - Differentiation of pleomorphic adenoma and Warthin's tumor of the parotid gland:
      ultrasonographic features.
AB  - BACKGROUND: Parotid tumor is an uncommon neoplasm. Only a few studies describing
      the sonographic features of pleomorphic adenomas and Warthin's tumors have been
      published, and most of those reports are based on a relatively small number of
      cases. PURPOSE: To define the sonographic characteristics of pleomorphic adenoma
      and Warthin's tumor in the parotid gland. MATERIAL AND METHODS: We
      retrospectively evaluated the sonographic features of 77 pleomorphic adenomas in
      70 patients and 93 Warthin's tumors in 61 patients. The features included tumor
      size, shape, border, echogenicity, and homogeneity, the presence of a cystic
      area, acoustic enhancement, and the grade and distribution of vascularization.
      RESULTS: Lobulated lesions were observed in 49 pleomorphic adenomas and 36
      Warthin's tumors. The lobulated shape was observed more frequently in pleomorphic
      adenomas than in Warthin's tumors (P = 0.005). Cystic areas within lesions were
      detected in 16 (16/77, 20.8%) pleomorphic adenomas and 42 (42/93, 45.2%)
      Warthin's tumors (P = 0.001). Of the pleomorphic adenomas, 77.9% had grade 0 or
      grade 1 vascularity, while 73.1% of Warthin's tumors had grade 2 or grade 3
      vascularity (P = 0.000). Flow was peripheral in 53.2% of pleomorphic adenomas.
      The frequencies of central perfusion and mixed perfusion in Warthin's tumors were
      equal (47.3% vs. 47.3%, respectively). The differences in the vessel distribution
      between these two diseases was significant (P = 0.000). CONCLUSION: Ultrasound
      imaging characteristics, including multiple occurrences, shape, intrinsic cystic
      change, and the grade and distribution of tumor vessels, can be used to
      differentiate pleomorphic adenomas from Warthin's tumors.

PMID- 24324277
TI  - Small molecule-mediated directed differentiation of human embryonic stem cells
      toward ventricular cardiomyocytes.
AB  - The generation of human ventricular cardiomyocytes from human embryonic stem
      cells and/or induced pluripotent stem cells could fulfill the demand for
      therapeutic applications and in vitro pharmacological research; however, the
      production of a homogeneous population of ventricular cardiomyocytes remains a
      major limitation. By combining small molecules and growth factors, we developed a
      fully chemically defined, directed differentiation system to generate ventricular
      like cardiomyocytes (VCMs) from human embryonic stem cells and induced
      pluripotent stem cells with high efficiency and reproducibility. Molecular
      characterization revealed that the differentiation recapitulated the
      developmental steps of cardiovascular fate specification. Electrophysiological
      analyses further illustrated the generation of a highly enriched population of
      VCMs. These chemically induced VCMs exhibited the expected cardiac
      electrophysiological and calcium handling properties as well as the appropriate
      chronotropic responses to cardioactive compounds. In addition, using an
      integrated computational and experimental systems biology approach, we
      demonstrated that the modulation of the canonical Wnt pathway by the small
      molecule IWR-1 plays a key role in cardiomyocyte subtype specification. In
      summary, we developed a reproducible and efficient experimental platform that
      facilitates a chemical genetics-based interrogation of signaling pathways during
      cardiogenesis that bypasses the limitations of genetic approaches and provides a
      valuable source of ventricular cardiomyocytes for pharmacological screenings as
      well as cell replacement therapies. 

PMID- 24324272
TI  - A habitable fluvio-lacustrine environment at Yellowknife Bay, Gale crater, Mars.
AB  - The Curiosity rover discovered fine-grained sedimentary rocks, which are inferred
      to represent an ancient lake and preserve evidence of an environment that would
      have been suited to support a martian biosphere founded on chemolithoautotrophy.
      This aqueous environment was characterized by neutral pH, low salinity, and
      variable redox states of both iron and sulfur species. Carbon, hydrogen, oxygen,
      sulfur, nitrogen, and phosphorus were measured directly as key biogenic elements;
      by inference, phosphorus is assumed to have been available. The environment
      probably had a minimum duration of hundreds to tens of thousands of years. These
      results highlight the biological viability of fluvial-lacustrine environments in
      the post-Noachian history of Mars. 

PMID- 24324279
TI  - Reduction mammaplasty and mastopexy in previously irradiated breasts.
AB  - BACKGROUND: Little data exist on the safety of elective breast surgery following
      breast conservation therapy. OBJECTIVES: The authors evaluate their experience
      performing reduction mammaplasties and mastopexies in previously irradiated
      breasts. METHODS: A retrospective chart review was conducted of all reduction
      mammaplasties and mastopexies in previously irradiated breasts performed by the 2
      senior authors (MYN and SLS) from 1995 to 2012 (n = 18). Patient records were
      analyzed for demographics, perioperative and postoperative details, and
      complications. RESULTS: During the study period, 12 reduction mammaplasties and 6
      mastopexies were performed on breasts previously treated with breast conservation
      therapy. The average study participant age was 49.5 years, and average body mass
      index was 29. Average preoperative bra cup size was D/DD. One patient was a
      former smoker; 17 were nonsmokers. Eleven of the 18 patients had been previously
      treated with chemotherapy; average time between radiation therapy and surgery was
      2.5 years. Average specimen weight in the 12 reduction mammaplasties was 623 g.
      Twenty-two percent (n = 4) of patients experienced a total of 5 minor
      complications; none required a return to the operating room. One patient (6%)
      experienced a major complication resulting in approximately 50% loss of breast
      tissue, which was reconstructed with a latissimus dorsi musculocutaneous flap.
      Seventeen patients (94%) had successful outcomes with preoperative goals
      achieved. CONCLUSIONS: In the previously irradiated breast, reduction mammaplasty
      and mastopexy should be approached with extra caution, but the surgeries may
      still be safely and successfully performed. LEVEL OF EVIDENCE: 4.

PMID- 24324281
TI  - A Nonparametric Prior for Simultaneous Covariance Estimation.
AB  - In the modeling of longitudinal data from several groups, appropriate handling of
      the dependence structure is of central importance. Standard methods include
      specifying a single covariance matrix for all groups or independently estimating
      the covariance matrix for each group without regard to the others, but when these
      model assumptions are incorrect, these techniques can lead to biased mean effects
      or loss of efficiency, respectively. Thus, it is desirable to develop methods to
      simultaneously estimate the covariance matrix for each group that will borrow
      strength across groups in a way that is ultimately informed by the data. In
      addition, for several groups with covariance matrices of even medium dimension,
      it is difficult to manually select a single best parametric model among the huge
      number of possibilities given by incorporating structural zeros and/or
      commonality of individual parameters across groups. In this paper we develop a
      family of nonparametric priors using the matrix stick-breaking process of Dunson
      et al. (2008) that seeks to accomplish this task by parameterizing the covariance
      matrices in terms of the parameters of their modified Cholesky decomposition
      (Pourahmadi, 1999). We establish some theoretic properties of these priors,
      examine their effectiveness via a simulation study, and illustrate the priors
      using data from a longitudinal clinical trial.

PMID- 24324280
TI  - Incorporating discrete event simulation into quality improvement efforts in
      health care systems.
AB  - Quality improvement (QI) efforts are an indispensable aspect of health care
      delivery, particularly in an environment of increasing financial and regulatory
      pressures. The ability to test predictions of proposed changes to flow, policy,
      staffing, and other process-level changes using discrete event simulation (DES)
      has shown significant promise and is well reported in the literature. This
      article describes how to incorporate DES into QI departments and programs in
      order to support QI efforts, develop high-fidelity simulation models, conduct
      experiments, make recommendations, and support adoption of results. The authors
      describe how DES-enabled QI teams can partner with clinical services and
      administration to plan, conduct, and sustain QI investigations. 

PMID- 24324273
TI  - In situ radiometric and exposure age dating of the martian surface.
AB  - We determined radiogenic and cosmogenic noble gases in a mudstone on the floor of
      Gale Crater. A K-Ar age of 4.21 +/- 0.35 billion years represents a mixture of
      detrital and authigenic components and confirms the expected antiquity of rocks
      comprising the crater rim. Cosmic-ray-produced (3)He, (21)Ne, and (36)Ar yield
      concordant surface exposure ages of 78 +/- 30 million years. Surface exposure
      occurred mainly in the present geomorphic setting rather than during primary
      erosion and transport. Our observations are consistent with mudstone deposition
      shortly after the Gale impact or possibly in a later event of rapid erosion and
      deposition. The mudstone remained buried until recent exposure by wind-driven
      scarp retreat. Sedimentary rocks exposed by this mechanism may thus offer the
      best potential for organic biomarker preservation against destruction by cosmic
      radiation. 

PMID- 24324282
TI  - "Click" and Olefin Metathesis Chemistry in Water at Room Temperature Enabled by
      Biodegradable Micelles.
AB  - The two laboratory reactions focus on teaching several concepts associated with
      green chemistry. Each uses a commercial, nontoxic, and biodegradable surfactant,
      TPGS-750-M, to promote organic reactions within the lipophilic cores of nanoscale
      micelles in water. These experiments are based on work by K. Barry Sharpless (an
      azide-alkyne "click" reaction) and Robert Grubbs (an olefin cross-metathesis
      reaction); both are suitable for an undergraduate organic laboratory. The copper
      catalyzed azide-alkyne [3+2] cycloaddition of benzyl azide and 4-tolylacetylene
      is very rapid: the triazole product is readily isolated by filtration and is
      characterized by thin-layer chromatography and melting point analysis. The
      ruthenium-catalyzed olefin cross-metathesis reaction of benzyl acrylate with 1
      hexene is readily monitored by thin-layer chromatography and gas chromatography.
      The metathesis experiment comparatively evaluates the efficacy of a TPGS-750
      M/water medium relative to a traditional reaction performed in dichloromethane (a
      common solvent used for olefin metathesis).

PMID- 24324283
TI  - Peer Associations and Coping: The Mediating Role of Ethnic Identity for Urban,
      African American Adolescents.
AB  - This study sought to examine the relationship between coping strategies and
      prosocial and deviant peer associations for urban, African American adolescents.
      In addition, the study analyzed the mediating role of ethnic identity for coping
      strategies and peer associations. Results of the African American models were
      then compared with models for European American adolescents. Results indicated
      that African American and European American adolescents who reported using
      distraction coping strategies were more likely to associate with prosocial peers,
      and those who reported using self-destruction strategies were less likely to
      associate with prosocial peers. Adolescents who reported using distraction coping
      strategies were less likely to associate with deviant peers, and adolescents who
      reported using self-destruction strategies were more likely to associate with
      deviant peers. Ethnic identity mediated the relationship between coping and
      prosocial peer association for African American adolescents. Limitations of the
      study and future research directions are also presented.

PMID- 24324284
TI  - Attention to Multiple Events Helps 2 1/2-Year-Olds Extend New Verbs.
AB  - An important question in verb learning is how children extend new verbs to new
      situational contexts. In Study 1, 2 1/2-year-old children were shown a complex
      event followed by new events that preserved only the action from the initial
      event, only the result, or no new events. Children seeing events that preserved
      either the action or the result produced appropriate verb extensions at test
      while children without this information did not. In a follow-up study, children
      hearing new verbs produced more extensions than did children hearing nonlabeling
      speech. These studies suggest that attention to related events is helpful to
      young verb learners, perhaps because they structurally align these events (e.g.,
      Gentner, 1983; 1989) during verb learning.

PMID- 24324275
TI  - Mars' surface radiation environment measured with the Mars Science Laboratory's
      Curiosity rover.
AB  - The Radiation Assessment Detector (RAD) on the Mars Science Laboratory's
      Curiosity rover began making detailed measurements of the cosmic ray and
      energetic particle radiation environment on the surface of Mars on 7 August 2012.
      We report and discuss measurements of the absorbed dose and dose equivalent from
      galactic cosmic rays and solar energetic particles on the martian surface for
      ~300 days of observations during the current solar maximum. These measurements
      provide insight into the radiation hazards associated with a human mission to the
      surface of Mars and provide an anchor point with which to model the subsurface
      radiation environment, with implications for microbial survival times of any
      possible extant or past life, as well as for the preservation of potential
      organic biosignatures of the ancient martian environment. 

PMID- 24324274
TI  - Elemental geochemistry of sedimentary rocks at Yellowknife Bay, Gale crater,
      Mars.
AB  - Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were
      derived from sources that evolved from an approximately average martian crustal
      composition to one influenced by alkaline basalts. No evidence of chemical
      weathering is preserved, indicating arid, possibly cold, paleoclimates and rapid
      erosion and deposition. The absence of predicted geochemical variations indicates
      that magnetite and phyllosilicates formed by diagenesis under low-temperature,
      circumneutral pH, rock-dominated aqueous conditions. Analyses of diagenetic
      features (including concretions, raised ridges, and fractures) at high spatial
      resolution indicate that they are composed of iron- and halogen-rich components,
      magnesium-iron-chlorine-rich components, and hydrated calcium sulfates,
      respectively. Composition of a cross-cutting dike-like feature is consistent with
      sedimentary intrusion. The geochemistry of these sedimentary rocks provides
      further evidence for diverse depositional and diagenetic sedimentary environments
      during the early history of Mars. 

PMID- 24324285
TI  - Clinical, MRI, and CSF markers of disability progression in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic disorder of the central nervous system (CNS)
      in which the complex interplay between inflammation and neurodegeneration
      determines varying degrees of neurological disability. For this reason, it is
      very difficult to express an accurate prognosis based on purely clinical
      information in the individual patient at an early disease stage. Magnetic
      resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers are promising
      sources of prognostic information with a good potential of quantitative measure,
      sensitivity, and reliability. However, a comprehensive MS outcome prediction
      model combining multiple parameters is still lacking. Current relevant literature
      addressing the topic of clinical, MRI, and CSF markers as predictors of MS
      disability progression is reviewed here. 

PMID- 24324276
TI  - Volatile and organic compositions of sedimentary rocks in Yellowknife Bay, Gale
      crater, Mars.
AB  - H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace
      gases were evolved during pyrolysis of two mudstone samples acquired by the
      Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing
      phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous
      materials. Thermal decomposition of carbonates and combustion of organic
      materials are candidate sources for the CO2. Concurrent evolution of O2 and
      chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides
      are likely sources for sulfur-bearing species. Higher abundances of chlorinated
      hydrocarbons in the mudstone compared with Rocknest windblown materials
      previously analyzed by Curiosity suggest that indigenous martian or meteoritic
      organic carbon sources may be preserved in the mudstone; however, the carbon
      source for the chlorinated hydrocarbons is not definitively of martian origin. 

PMID- 24324286
TI  - Investigation of genetic polymorphisms related to the outcome of radiotherapy for
      prostate cancer patients.
AB  - The purpose of this study was to evaluate the association between ATM, TP53 and
      MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy.
      The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362,
      rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by
      direct sequencing of PCR fragments from 48 patients with histologically proven
      prostate adenocarcinoma and treated with external beam radiation. The side
      effects were classified according to the Radiation Therapy Oncology Group (RTOG)
      score. The results showed no association between clinical characteristics and the
      development of radiation toxicities (P > 0.05). The C>T transition in the
      position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with
      the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002-0.227, P = 0.003). The
      intronic TP53 polymorphism at position 16250 (rs17883323) was associated with
      chronic urinary toxicity (OR: 0.071, 95%CI 0.006-0.784, P = 0.032). No
      significant associations were found for the remaining polymorphisms (P > 0.05).
      The results show that clinical characteristics were not determinant on the
      developing of radiation sensitivity in prostate cancer patients, and intronic
      TP53 polymorphisms would be associated with increased acute and chronic radiation
      toxicities. These observations corroborate the importance of investigating the
      genetic profile to predict adverse side effects in patients undergoing
      radiotherapy. 

PMID- 24324287
TI  - Mast cells as a potential prognostic marker in prostate cancer.
AB  - Despite years of intensive investigation that has been made in understanding
      prostate cancer, it remains one of the major men's health issues and the leading
      cause of death worldwide. It is now ascertained that prostate cancer emerges from
      multiple spontaneous and/or inherited alterations that induce changes in
      expression patterns of genes and proteins that function in complex networks
      controlling critical cellular events. It is now accepted that several innate and
      adaptive immune cells, including T- and B-lymphocytes, macrophages, natural
      killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs),
      infiltrate the prostate cancer. All of these cells are irregularly scattered
      within the tumor and loaded with an assorted array of cytokines, chemokines, and
      inflammatory and cytotoxic mediators. This complex framework reflects the
      diversity in tumor biology and tumor-host interactions. MCs are well-established
      effector cells in Immunoglobulin-E (Ig-E) associated immune responses and potent
      effector cells of the innate immune system; however, their clinical significance
      in prostate cancer is still debated. Here, these controversies are summarized,
      focusing on the implications of these findings in understanding the roles of MCs
      in primary prostate cancer. 

PMID- 24324288
TI  - Risk of preterm delivery associated with prior treatment of cervical precancerous
      lesion according to the depth of the cone.
AB  - The aim of this study was to evaluate the impact of the surgical excisional
      procedures for cervical intraepithelial neoplasia (CIN) treatment both on
      subsequent fertility (cervical factor) and pregnancy complication (risk of
      spontaneous preterm delivery). We retrospectively analyzed 236 fertile women who
      underwent conization for CIN. We included in the study 47 patients who carried on
      pregnancy and delivered a viable fetus. Patients were asked about postconization
      pregnancies, obstetrical outcomes, and a possible diagnosis of secondary
      infertility caused by cervical stenosis. We evaluated the depth of surgical
      excision, the timing between cervical conization and subsequent pregnancies,
      surgical technique, and maternal age at delivery. We recorded 47 deliveries, 10
      cases of preterm delivery; 8 of them were spontaneous. The depth of surgical
      excision showed a statistically significant inverse correlation with gestational
      age at birth. The risk of spontaneous preterm delivery increased when conization
      depth exceeded a cut-off value of 1.5 cm. Our data do not demonstrated a relation
      between conization and infertility due to cervical stenosis.

PMID- 24324291
TI  - Recruitment and retention of voluntary blood donors through electronic
      communication.

PMID- 24324290
TI  - Predictive value of admission N-terminal pro-B-type natriuretic peptide and renal
      function in older people hospitalized for dyspnoea.
AB  - BACKGROUND: We investigated the relationship between NT-pro-BNP, glomerular
      filtration rate (GFR), and all-cause mortality rates in a cohort of older people
      discharged from an internal medicine unit after admission for dyspnoea. PATIENTS
      AND METHODS: NT-pro-BNP was evaluated in serum samples of 134 patients aged 80 +/
      6 years who presented to a single academic centre with worsening dyspnoea.
      History data and anthropometric, clinical, and biochemical parameters including
      GFR were collected at the time of admission. 119 out of 134 were discharged alive
      from hospital and were included in the follow-up of 779 +/- 370 days. RESULTS: 35
      out of 119 subjects died after a follow-up of 266 +/- 251 days. Cox proportional
      hazards model showed that GFR and Ln (NT-pro-BNP) were predictors for all-cause
      mortality with estimated hazard ratios of 0.969 (95% confidence interval: 0.950
      0.988; P = 0.001) and 2.360 (95% confidence interval: 1.208-4.610; P = 0.012),
      respectively. Patients characterized by high NT-pro-BNP levels and GFR >= 60
      mL/min/1.73 m(2) showed a dramatic reduction in survival duration compared with
      the groups with different combinations of the two variables (P = 0.008).
      CONCLUSIONS: In the elderly, NT-pro-BNP and GFR are predictors of all-cause
      mortality after admission because of dyspnoea. Since the fact that subjects with
      high NT-pro-BNP and GFR >= 60 mL/min/1.73 m(2) exhibited a reduced survival, high
      admission NT-pro-BNP suggests future negative outcome.

PMID- 24324289
TI  - Rheumatoid factors: clinical applications.
AB  - Rheumatoid factors are antibodies directed against the Fc region of
      immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years
      ago, they can also be found in patients with other autoimmune and nonautoimmune
      conditions, as well as in healthy subjects. Rheumatoid factors form part of the
      workup for the differential diagnosis of arthropathies. In clinical practice, it
      is recommended to measure anti-cyclic citrullinated peptide antibodies and
      rheumatoid factors together because anti-cyclic citrullinated peptide antibodies
      alone are only moderately sensitive, and the combination of the two markers
      improves diagnostic accuracy, especially in the case of early rheumatoid
      arthritis. Furthermore, different rheumatoid factor isotypes alone or in
      combination can be helpful when managing rheumatoid arthritis patients, from the
      time of diagnosis until deciding on the choice of therapeutic strategy. 

PMID- 24324292
TI  - Osteomyelitis after robotically assisted laparoscopic sacral colpopexy.

PMID- 24324293
TI  - Inflammatory mechanisms of idiopathic epiretinal membrane formation.
AB  - The pathogenesis of idiopathic epiretinal membranes (iERMs), a common pathology
      found in retina clinics, still eludes researchers to date. Ultrastructural
      studies of iERMs in the past have failed to identify the cells of origin due to
      the striking morphologic changes of cells involved via transdifferentiation.
      Thus, immunohistochemical techniques that stain for the cytostructural components
      of cells have confirmed the importance of glial cells and hyalocytes in iERM
      formation. The cellular constituents of iERMs are thought to consist of glial
      cells, fibroblasts, hyalocytes, etc. that, in concert with cytokines and growth
      factors present in the vitreous, lead to iERM formation. Recently, research has
      focused on the role of the posterior hyaloid in iERM formation and contraction,
      particularly the process of anomalous PVD as it relates to iERM formation. Recent
      advances in proteomics techniques have also elucidated the growth factors and
      cytokines involved in iERM formation, most notably nerve growth factor, glial
      cell line-derived growth factor, and transforming growth factor beta1.

PMID- 24324294
TI  - Actin is a target of T-cell reactivity in patients with advanced carotid
      atherosclerotic plaques.
AB  - Atherosclerosis is a chronic inflammatory disease of the arterial wall associated
      with autoimmune reactions. In a previous study, we observed the presence of actin
      specific antibodies in sera from patients with carotid atherosclerosis. To extend
      our previous results we evaluated the possible role of actin as antigenic target
      of cell-mediated immune reactions in carotid atherosclerosis. Peripheral blood
      mononuclear cells (PBMC) from 17 patients and 16 healthy subjects were tested by
      cell proliferation assay and by ELISA for cytokine production. Actin induced a
      proliferative response in 47% of patients' PBMC samples, with SI ranging from 2.6
      to 21.1, and in none of the healthy subjects' samples (patients versus healthy
      subjects, P = 0.02). The presence of diabetes in patients was significantly
      associated with proliferative response to actin (P = 0.04). IFN- gamma and TNF-
      alpha concentrations were higher in PBMC from patients than in those from healthy
      subjects and in PBMC proliferating to actin than in nonproliferating ones. Our
      data demonstrate for the first time a role of actin as a target autoantigen of
      cellular immune reactions in patients with carotid atherosclerosis. The
      preferential proinflammatory Th1 activation suggests that actin could contribute
      to endothelial dysfunction, tissue damage, and systemic inflammation in carotid
      atherosclerosis. 

PMID- 24324295
TI  - PD-L1 blockade attenuated sepsis-induced liver injury in a mouse cecal ligation
      and puncture model.
AB  - Liver plays a major role in hypermetabolism and produces acute phase proteins
      during systemic inflammatory response syndrome and it is of vital importance in
      host defense and bacteria clearance. Our previous studies indicated that
      programmed death-1 (PD-1) and its ligand programmed death ligand-1 (PD-L1) are
      crucial modulators of host immune responses during sepsis. Our current study was
      designed to investigate the role of PD-L1 in sepsis-induced liver injury by a
      mouse cecal ligation and puncture (CLP) model. Our results indicated that there
      was a significant increase of PD-L1 expression in liver after CLP challenge
      compared to sham-operated controls, in terms of levels of mRNA transcription and
      immunohistochemistry. Anti-PD-L1 antibody significantly alleviated the morphology
      of liver injury in CLP mice. Anti-PD-L1 antibody administration decreased ALT and
      AST release in CLP mice, decreased the levels of tumor necrosis factor (TNF)
      alpha , interleukin (IL)-6, and IL-10 mRNA in liver after sepsis challenge. Thus,
      anti-PD-L1 antibody might have a therapeutic potential in attenuating liver
      injury in sepsis.

PMID- 24324297
TI  - Clinical consequences of untreated dental caries evaluated using PUFA index in
      orphanage children from India.
AB  - BACKGROUND: To determine the prevalence and severity of oral condition related to
      untreated dental caries with PUFA index and to relate period of institutional
      stay, oral hygiene practice and diet of orphan children to caries experience
      ratio. MATERIALS & METHODS: A cross sectional survey conducted among 488 children
      of 12-14 years living in 5 different orphanages of Mysore district, India. Data
      regarding oral hygiene practices and oral health status (PUFA, DMFT, OH I-S and
      GI) were collected through structured questionnaire and by type III clinical oral
      examinations. The collected data were processed statistically. RESULTS: The PUFA
      ratio indicates 21% of decayed component had progressed to pulp involvement and
      abscess formation. The overall prevalence of PUFA was 37.7%. 31.1% children
      showed one or more pulpally involved tooth in their oral cavity. Correlation
      between periods for being the child in the institute to DMFT showed negative
      value indicting decrease in DMFT as the duration of stay in orphanage increases.
      CONCLUSION: The result show oral health condition in orphan children was
      neglected. Children from this disadvantaged background have shown a high
      prevalence of dental caries with low dental care utilization. PUFA index is an
      effective index in evaluating clinical consequences of un-treated caries. How to
      cite this article: Shanbhog R, Godhi BS, Nandlal B, Kumar SS, Raju V, Rashmi S.
      Clinical consequences of untreated dental caries evaluated using PUFA index in
      orphanage children from India. J Int Oral Health 2013; 5(5):1-9.

PMID- 24324296
TI  - Chemokines and neurodegeneration in the early stage of experimental ischemic
      stroke.
AB  - Neurodegeneration is a hallmark of most of the central nervous system (CNS)
      disorders including stroke. Recently inflammation has been implicated in
      pathogenesis of neurodegeneration and neurodegenerative diseases. The aim of this
      study was analysis of expression of several inflammatory markers and its
      correlation with development of neurodegeneration during the early stage of
      experimental stroke. Ischemic stroke model was induced by stereotaxic
      intracerebral injection of vasoconstricting agent endothelin-1 (ET-1). It was
      observed that neurodegeneration appears very early in that model and correlates
      well with migration of inflammatory lymphocytes and macrophages to the brain.
      Although the expression of several studied chemotactic cytokines (chemokines) was
      significantly increased at the early phase of ET-1 induced stroke model, no clear
      correlation of this expression with neurodegeneration was observed. These data
      may indicate that chemokines do not induce neurodegeneration directly.
      Upregulated in the ischemic brain chemokines may be a potential target for future
      therapies reducing inflammatory cell migration to the brain in early stroke.
      Inhibition of inflammatory cell accumulation in the brain at the early stage of
      stroke may lead to amelioration of ischemic neurodegeneration. 

PMID- 24324298
TI  - Prevalence of Dental Anomalies among School Going Children in India.
AB  - BACKGROUND: The purpose of the present study is to investigate the prevalence of
      dental anomalies according to gender among children. MATERIALS & METHODS: This
      cross-sectional study was conducted a group of 600 children, of them 293 (48.8%)
      were males and 275 (45.8%) females which were taken with proper sampling
      technique. Type III clinical examination was done to know the prevalence of
      dental anomalies. The Statistical software namely SPSS version 16.0 was used for
      data analysis. Chi-square test was used at p value of 0.05 or less. RESULTS:
      Impactions (39.2%) were the most common anomaly in this study and most of the
      impacted teeth were related to maxilla. A significant difference was seen in case
      of hypodontia, microdontia and talons cusp according to gender in which first two
      anomalies were more among females and last one among males. Children with one
      dental anomaly were 25.8%, and 13.4% were having more than one. CONCLUSION: The
      percentage of dental anomalies were high specially impaction and rotated teeth.
      So these anomalies should be treated earlier to avoid further complications. How
      to cite this article: Kathariya MD, Nikam AP, Chopra K, Patil NN, Raheja H,
      Kathariya R. Prevalence of Dental Anomalies among School Going Children in India.
      J Int Oral Health 2013; 5(5):10-4.

PMID- 24324299
TI  - Epidemiological Study to Evaluate the Prevalence of Dentine Hypersensitivity
      among Patients.
AB  - BACKGROUND: Dentine hypersensitivity (DH) is a common finding with different
      prevalence rate. The aim of this study was to evaluate the prevalence of DH and
      associated risk factors. MATERIALS & METHODS: This cross-sectional survey was
      done among patients coming to dental hospital. The diagnosis of DH was made as
      the result of both clinical examination and patient's response. A self
      administered structured questionnaire was used to know demography profile, self
      reported DH, the activating factors, preventive measures and frequency.
      Descriptive statistics were obtained and frequency distribution was calculated
      using Chi square t test at p value <0.05. RESULTS: The total population
      compromised of 960 patients including 528 males and 432 females. The prevalence
      of dentine hypersensitivity in this sample was 42.5% and more common among male
      population (60.8%) and the peak age was between 30 to 39 years (39.2%). Lower
      anteriors were commonly involved (35.8%) and cold drinks (25.8%) are the main
      aggravating factor. 6.5% experience it all the time but still some do not take
      preventive measures. CONCLUSION: There is high prevalence rate of DH and mainly
      among males. Some of the patients had it all the time but still they do not want
      to control the problem. How to cite this article:Rane P, Pujari S, Patel P,
      Gandhewar M, Madria K, Dhume S. Epidemiological Study to Evaluate the Prevalence
      of Dentine Hypersensitivity among Patients. J Int Oral Health 2013; 5(5):15-9.

PMID- 24324300
TI  - MSX1 gene variant - its presence in tooth absence - a case control genetic study.
AB  - BACKGROUND: Non Syndromic tooth agenesis is a congenital anomaly with significant
      medical, psychological and social ramifications. There is sufficient evidence to
      hypothesize that locus for this condition can be identified by candidate genes.
      The aim of this study was to test whether MSX1 671 T>C gene variant was involved
      in etiology of Non Syndromic tooth agenesis in Raichur Patients. MATERIALS &
      METHODS: Blood samples were collected with informed consent from 50 subjects
      having Non Syndromic tooth agenesis and 50 controls. Genomic DNA was extracted
      from the blood samples, Polymerase Chain Reaction was performed (PCR) and
      Restriction Fragment Length Polymorphism (RFLP) was performed for digestion
      products that were evaluated. RESULTS: The RESULTS showed positive correlation
      between MSX1671 T>C gene variant and Non Syndromic tooth agenesis in Raichur
      Patients. CONCLUSION: MSX1 671 T>C gene variant may be a good screening marker
      for Non Syndromic tooth agenesis in Raichur Patients . How to cite this
      article:Reddy NA, Adusumilli G, Devanna R, Pichai S, Rohra MG, Arjunan S. Msx1
      Gene Variant - Its Presence in Tooth Absence - A Case Control Genetic Study. J
      Int Oral Health 2013; 5(5):20-6.

PMID- 24324301
TI  - To evaluate and compare the effect of different Post Surface treatments on the
      Tensile Bond Strength between Fiber Posts and Composite Resin.
AB  - BACKGROUND: Fiber posts are widely used for restoration of mutilated teeth that
      lack adequate coronal tooth structure to retain a core for definitive
      restoration, bond between the fiber post and composite material depends upon the
      chemical reaction between the post surface and the resin material used for
      building up the core. In attempt to maximize the resin bonding with fiber post,
      different post surface conditioning is advocated. Therefore the purpose of the
      study is to examine the interfacial strength between fiber post and composite, as
      core build-up material after different surface treatments of fiber posts.
      MATERIALS & METHODS: Twenty fiber posts were split into four groups off five each
      according to different surface treatments viz. Group I-(Negative Control), Group
      II-Silanization (Positive control), Group III-(37% Phosphoric Acid &
      Silanization) ,Group IV- (10% Hydrogen Peroxide and Silanization). With the
      preformed plastic mould, a core of dual cure composite resin around the fiber
      post having the uniform thickness was created. Tensile bond strength of each
      specimen was measured under Universal Testing Machine (UTM) at the cross head
      speed of 3mm/min. RESULTS: The results achieved with 10% Hydrogen peroxide had a
      marked effect on micro tensile bond strength values between the tested materials.
      CONCLUSION: Immense enhancement in the silanization efficiency of quartz fiber
      phase was observed with different surface chemical treatment of the resin phase
      of fiber posts with the marked increase in the micro-tensile bond strength
      between fiber post and composite core. HOW TO CITE THIS ARTICLE: Shori D, Pandey
      S, Kubde R, Rathod Y, Atara R, Rathi S. To evaluate and compare the effect of
      different Post Surface treatments on the Tensile Bond Strength between Fiber
      Posts and Composite Resin. J Int Oral Health 2013; 5(5):27-32.

PMID- 24324302
TI  - Evaluation of the efficacy of probiotics in plaque reduction and gingival health
      maintenance among school children - A Randomized Control Trial.
AB  - BACKGROUND: Probiotics are live micro-organisms that when administered in
      adequate amounts confer health benefits upon the host. The impact of probiotics
      on oral health is relatively new with lots of research going on; the area of
      probiotics and periodontal disease is still in its infancy. The aim of the
      present trial was to evaluate the efficacy of the probiotics in plaque reduction
      among school children. MATERIALS & METHODS: This is a randomized, double-blind,
      placebo controlled parallel design study involving 216 school children (aged 14 -
      17 years): 108 as experimental subjects and 108 as controls. Complete oral
      prophylaxes were performed for both the control group and experimental group. The
      pre-intervention plaque index and gingival index were recorded one week after the
      prophylaxis for both groups as the baseline data. The study subjects (Group A)
      included curd in their daily diet for 30 days, while the control subjects (Group
      B) excluded curd in their diet for 30 days. The post intervention plaque index
      and gingival index were recorded again and statistically compared with the
      baseline data. RESULTS: the intervention group (Group A) was found to have
      statistically significant reduction in plaque when compared to that of the
      control group with p <0.001 and there was no significant improvement in gingival
      health. CONCLUSION: A short-term daily ingestion of probiotics delivered via curd
      in diet reduced the levels of plaque. Hence if it can be promoted in the regular
      diet, it would help in improving the oral health among school children. How to
      cite this article: Karuppaiah RM, Shankar S, Raj SK, Ramesh K, Prakash R,
      Kruthika M. Evaluation of the efficacy of probiotics in plaque reduction and
      gingival health maintenance among school children - A Randomized Control Trial. J
      Int Oral Health 2013; 5(5):33-7.

PMID- 24324303
TI  - Validation of a Kannada version of the Impact of Events Scale (IES).
AB  - BACKGROUND: This study presents a Kannada translation and validation of the
      Impact of Event Scale in a population of men and women exposed to maxillofacial
      trauma and orthopedic/ general trauma. MATERIALS & METHODS: A total of 96 study
      subjects from multi modal trauma centers in Bangalore city completed the Kannada
      translated questionnaire at the time of discharge, the first post- operative
      month and the sixth month of follow up. RESULTS: The Kannada IES is reliable when
      analyzed with the students T-test, it has good internal consistency with
      Cronbach's alpha-coefficients ranging from .970 to .974, the test-retest
      reliability with Karl Pearson's correlation of the scale at all three time
      intervals showed significant correlation. A principal component analysis was
      conducted to ascertain the validity and two components were derived from the 15
      questions which were able to explain 88% of the variation and the two were
      retained (intrusion and avoidance). CONCLUSION: The Kannada version of the IES
      has satisfactory reliability, internal validity, test-retest reliability and the
      factor structure was similar to the proposed theoretical structure of the IES.
      How to cite this article: Tavane PN, Raghuveer HP, Kumar RD, Shobha ES, Rangan V,
      Dutt CS. Validation of a Kannada version of the Impact of Events Scale (IES). J
      Int Oral Health 2013; 5(5):38-47.

PMID- 24324304
TI  - Awareness among patients regarding Implants as a treatment option for replacement
      of missing teeth in Chattisgarh.
AB  - BACKGROUND: This survey was done to know awareness of patients regarding dental
      implants as a treatment option for replacement of missing teeth. MATERIALS &
      METHODS: This cross sectional study was done among 483 subjects coming to dental
      college using a self administered structured questionnaire. The questionnaire was
      pre-tested through a pilot survey. The data were analyzed using the SPSS version
      16.0. The Student's T-test and ANOVA test were used as test of significance at p
      < 0.05. RESULTS: Out of 483 participants, 290 were males and 193 females. Around
      41.7% of the subjects were aware of dental implants but still few (4.1%) had
      undergone this procedure. Dental professionals were the main source of
      information followed by media about implants and level of awareness increased
      with education. High cost of the procedure was the main factor for not undergoing
      treatment procedure (35.2%). CONCLUSION: More than half of the participants were
      not having information regarding implants and very few had undergone this
      procedure. It also showed that need for providing more information to the
      patients about this treatment modality. So, dental education is necessary for
      developing positive attitude among population regarding dental implants. How to
      cite this article: Saha A, Dutta S, Vijaya V, Rajnikant N. Awareness among
      patients regarding Implants as a treatment option for replacement of missing
      teeth in Chattisgarh. J Int Oral Health 2013; 5(5):48-52.

PMID- 24324305
TI  - Dental and periodontal health status of Beta thalassemia major and sickle cell
      anemic patients: a comparative study.
AB  - BACKGROUND: This study aimed to assess the dental and periodontal health status
      of beta thalassemia major and sickle cell anemic patients in Bilaspur,
      Chattishgarh, India. MATERIALS & METHODS: A total of 750 patients were included
      in the study. The patients were randomly divided into three groups I (n=250), II
      (n=250) and III (n=250), ranging from 3-15 years. After performing a thourough
      general examination, including their demographic data, intraoral examination was
      done using Decayed-Missing-Filled Teeth Index (DMFT Index), Plaque index (PI) and
      Gingival index (GI). Statistical analysis was done using statistical software
      SPSS 17.5 version. Chi square test & student t test was used for the comparison
      of study and control groups. The level of significance was set at P<0.05.
      RESULTS: In the present study, it was found that, prevalence of dental caries and
      periodontal diseases was significantly more in beta thalassemic patients followed
      by sickle cell anemic patients than control group. However, when group I (beta
      thalassemia) was compared with group II (sickle cell anemia), results were found
      to highly significant (P<0.001) only for decayed missing filled tooth.
      CONCLUSION: Appropriate dental and periodontal care improves a patient's quality
      of life. Preventive dental care is must for thalassemic and Sickle cell disease
      patients. How to cite this article: Singh J, Singh N, Kumar A, Kedia NB, Agarwal
      A. Dental and Periodontal Health Status of Beta Thalassemia Major and Sickle Cell
      Anemic Patients: A Comparative Study. J Int Oral Health 2013; 5(5):53-8.

PMID- 24324306
TI  - Comparative evaluation of the efficiency of four ceramic finishing systems.
AB  - AIM: To compare the effect of four different finishing systems and diamond paste
      on ceramic roughness with the objectives of evaluating the roughness of ceramic
      surface of prepared specimens after abrasion, finishing and polishing. MATERIALS
      & METHODS: A total of 50 test specimens were fabricated in the form of discs of
      diameter 13mm and 0.6mm thickness. Test specimens were then randomly distributed
      into five groups of 10 and coded. All the test specimens were then abraded with
      125MUm diamond in unidirectional motion to create surface roughness that will
      simulate occlusal or incisal correction. The values were recorded and the
      specimens were then finished using the various finishing systems. multiple range
      tests by Duncan's procedure. One way Anova was used to calculate the p-value
      Results:After fini shing, the Ra,Rq,Rz and Rt values showed a tendency to decline
      to levels much inferior to the values obtained after the preparation of the
      specimens. Ra values of group III specimens were slightly higher and the increase
      was significant. The highest Rt value [5.29] obtained after polishing is below
      the lowest roughness values [7.42] obtained after finishing the specimens.
      CONCLUSIONS: Finishing and polishing procedures have a significant role in
      reducing the roughness of ceramics.Following abrasion with diamond point to
      simulate clinical adjustment the roughness values doubled when compared to the
      initial reading.Ra, Rq,Rz and Rt values suggest that Sof lex is the most
      efficient of all the systems tested followed by auto glazing.After the final
      diamond paste polishing, sof lex group specimens showed the best finish and auto
      glazed specimens showed a value almost as equal to the so flex group. How to cite
      this article: Aravind P, Razak PA, Francis PG, Issac JK, Shanoj RP, Sasikumar TP.
      Comparative Evaluation of the Efficiency of Four Ceramics Finishing Systems. J
      Int Oral Health 2013; 5(5):59-64.

PMID- 24324308
TI  - An in vitro Comparative Evaluation of Micro Tensile Bond Strength of Two metal
      bonding Resin Cements bonded to Cobalt Chromium alloy.
AB  - BACKGROUND: The purpose of this study was to evaluate and compare the micro
      tensile bond strength of two metal bonding resin cements to sandblasted cobalt
      chromium alloy. MATERIALS & METHODS: Eight, Cobalt chromium alloy blocks of
      dimensions 10x5x5 mm were cast, finished and polished. One of the faces of each
      alloy block measuring 5x5mm was sandblasted with 50 MUm grit alumina particles.
      The alloy blocks were then cleaned in an ultrasonic cleaner for 1 min and then
      air dried with an air stream. The Sandblasted surfaces of the two alloy blocks
      were bonded together with 2 different metal bonding resin systems (Panavia F
      Kuraray and DTK Kleber - Bredent). The samples were divided into 2 groups (n=4).
      Group 1- Two Co-Cr blocks were luted with Panavia cement. Group 2- Two Co-Cr
      blocks were luted with DTK Kleber-Bredent cement. The bonded samples were cut
      with a diamond saw to prepare Microtensile bars of approximately 1mm x 1mm x 6mm.
      Thirty bars from each group were randomly separated into 2 subgroups (n=15) and
      left for 3hrs (baseline) as per manufacturer's instructions while the other group
      was aged for 24hrs in 370C water, prior to loading to failure under tension at a
      cross head speed of 1mm/min. Failure modes were determined by means of
      stereomicroscopy (sm). Statistical analysis was performed through one way -
      ANOVA. RESULTS: Significant variation in micro-tensile bond strength was observed
      between the two metal bonding resin systems. CONCLUSION: DTK showed higher mean
      bond strength values than Panavia F cement both at baseline and after aging. How
      to cite this article: Musani S, Musani I, Dugal R, Habbu N, Madanshetty P, Virani
      D. An in vitro Comparative Evaluation of Micro Tensile Bond Strength of Two metal
      bonding Resin Cements bonded to Cobalt Chromium alloy. J Int Oral Health
      2013;5(5):73-8.

PMID- 24324307
TI  - Quantitative estimation of Serum Fibrinogen Degradation Product levels in Oral
      Premalignant and Malignant lesions.
AB  - BACKGROUND: A specific association between cancer and the hemostatic system has
      been recognized for decades. Fibrinogen degradation product (FDP) is one of the
      factors, which opposes coagulation causing fibrinolysis. The mechanism of
      fibrinolysis can be used by the malignant cells to facilitate invasion into
      surrounding tissues and metastases to distant organs by breaking the fibrin
      barrier. The coagulation cascade also plays an important role in both the
      formation of tumour stroma and the promotion of hematogenous metastasis. The
      present study was undertaken to evaluate the serum FDP levels in individuals
      without any oral lesions and those with oral premalignant and malignant lesions,
      and determine whether the estimation of the same can be used as an aid in early
      diagnosis. MATERIALS & METHODS: 25 cases each of Leukoplakia, Oral submucous
      fibrosis and Oral squamous cell carcinomas (OSCC) and normal control cases were
      selected. The OSCC cases were staged according to the TNM classification.
      Diagnosis of all cases was confirmed by histopathological examination. The
      aspirated serum was then subjected to the Thrombo-Wellco test which was used for
      the biochemical analysis of FDP. RESULTS: Increased serum FDP levels were seen
      corresponding to the stage of the OSCC, but no appreciable difference was noted
      between the histological grades or in cases of premalignant lesions. CONCLUSIONS:
      The study demonstrates that FDP levels correlate with the cancer stage and
      progression. Thus, the estimation of serum FDP levels can be used as a reliable
      prognostic indicator and as a biologic marker of tumour spread How to cite this
      article: Gharat L, Rathod GP. Quantitative estimation of Serum Fibrinogen
      Degradation Product levels in Oral Premalignant and Malignant lesions. J Int Oral
      Health 2013; 5(5):65-72.

PMID- 24324309
TI  - Effect of Ozonised water on Chronic Periodontitis - A Clinical Study.
AB  - BACKGROUND: The aim of the study was to study the clinical effects of ozonated
      water on periodontal tissues. MATERIALS & METHODS: In the present study 30
      subjects were selected with age ranging from 20 to 60 yearsand pocket depth of
      >=5mm. Two sites were selected in each patient whichwere divided into two groups.
      Group 1(control group-irrigation with saline) and Group 2(study group-irrigation
      with ozonized water) and clinical parameters were recorded at baseline, 15 days
      and 30 days. RESULTS: When the comparison of mean values of Plaque Index and
      Gingival Index between the groups and at different time intervals were made,
      statistically significant difference were observed at 30 days at 5% level. When
      the mean values of clinical attachment level on mesial and distal site was
      compared between the groups, statistical significance was observed at 5% level
      and 1% level respectively.Similarly statistical significance at 5% level was
      observed at 15 and 30 days on buccal site. CONCLUSION: Subgingival irrigation
      with ozonized water is beneficial adjunct treatment modality to enhance
      periodontal health with significant role in periodontal therapy. How to cite this
      article: Katti SS, Chava VK. Effect of Ozonised water on Chronic Periodontitis -
      A Clinical Study. J Int Oral Health 2013;5(5):79-84.

PMID- 24324310
TI  - Comparative evaluation of dimensional accuracy of different polyvinyl siloxane
      putty-wash impression techniques-in vitro study.
AB  - BACKGROUND: Dimensional accuracy when making impressions is crucial to the
      quality of fixed prosthodontic treatment, and the impression technique is a
      critical factor affecting this accuracy. The purpose of this in vitro study was
      to compare the dimensional accuracy of the casts obtained from one step double
      mix, two step double mix polyvinyl siloxane putty- wash impression techniques
      using three different spacer thicknesses (0.5mm, 1mm and 1.5mm), in order to
      determine the impression technique that displays the maximum linear dimensional
      accuracy. MATERIALS & METHODS: A Mild steel model with 2 abutment preparations
      was fabricated, and impressions were made 15 times with each technique. All
      impressions were made with an addition-reaction silicone impression material
      (Express, 3M ESPE) and customarily made perforated metal trays. The 1-step
      putty/light-body impressions were made with simultaneous use of putty and light
      body materials. The 2-step putty/light-body impressions were made with 0.5-mm,
      1mm and 1.5mm-thick metal-prefabricated spacer caps. The accuracy of the 4
      different impression techniques was assessed by measuring 7 dimensions (intra-
      and inter abutment) (20-MUm accuracy) on stone casts poured from the impressions
      of the mild steel model. The data were analyzed by one sample't' test. RESULTS:
      The stone dies obtained with all the techniques had significantly larger or
      smaller dimensions as compared to those of the mild steel model (P<0.05). The
      order for highest to lowest deviation from the mild steel model was: single step
      putty/light body, 2-step putty/light body with 0.5mm spacer thickness, 2-step
      putty/light body1.5mm spacer thickness, and 2-step putty/light body with 1mm
      spacer thickness. Significant differences among all of the groups for both
      absolute dimensions of the stone dies, and their standard deviations from the
      master model (P<0.05), were noted. CONCLUSIONS: The 2-step putty/light-body
      impression technique with 1mm spacer thickness was most dimensionally accurate
      impression methods in terms of resultant casts. How to cite this article: Dugal
      R, Railkar B, Musani S. Dimensional accuracy when making impressions is crucial
      to the quality of fixed prosthodontic treatment, and the impression technique is
      a critical factor affecting this accuracy. J Int Oral Health 2013;5(5):85-94.

PMID- 24324311
TI  - Comparison between Silk Sutures and Cyanoacrylate Adhesive in Human Mucosa- A
      Clinical and Histological Study.
AB  - BACKGROUND: Closing the surgical incision is an important step in the surgical
      procedures, the success of surgery is sometimes compromised by the defective
      suturing techniques or improper suturing materials, black silk sutures are more
      or less most often used materials in the day today surgical procedures, but these
      suture materials demand more time and effort from the surgeon and there is a need
      to substitute these materials with more user friendly and more successful wound
      closing materials such as cyanoacrylates. This study intends to compare
      effectiveness of the black silk sutures with cyanoacrylate adhesives in closing
      the surgical incisions. MATERIALS & METHODS: 10 patients of age group between 15
      30 years who underwent bilateral apicoetomy were given 3-0 black silk sutures on
      one side and n-butyl-2cyanoacrylate adhesive on the other side of the frenum to
      close the surgical incision, and a clinical comparison was made on the 1st, 2nd,
      3rd, and 7th post-operative days, on the seventh postoperative day following
      removal of sutures, small punch biopsies were obtained from both the sites and
      the tissue specimens were examined under transmission electron microscope.
      RESULTS: Clinical observations revealed that on the 3rd and 7th postoperative
      days epithelialization was better on the sides treated with n-butyl
      2cyanoacrylate but the sites closed with black silk suture showed significant
      inflammation and scar formation , electron microscopic observation of both tissue
      specimens revealed that sutured tissue specimens showed dense inflammatory
      infiltrate but the sites treated with cyanoacrylate adhesive showed less
      inflammatory infiltrate and uniform distribution of neutrophils, lymphocytes,
      histocytes and eosinophils unlike the sutured specimens which showed more scar
      tissue and dense infiltrate concentrated along the margins of the gap.
      CONCLUSION: This study has indicated that the use of cyanoacrylate glue has
      resulted in less postoperative inflammation and good clinical and histological
      healing when compared to the silk sutures. How to cite this article: Kumar MS,
      Natta S, Shankar G, Reddy SH, Visalakshi D, Seshiah GV. Comparison between Silk
      Sutures and Cyanoacrylate Adhesive in Human Mucosa- A Clinical and Histological
      Study. J Int Oral Health 2013;5(5):95-100.

PMID- 24324312
TI  - In-vitro investigation to evaluate the flexural bond strengths of three
      commercially available ultra low fusing ceramic systems to Grade II Titanium.
AB  - BACKGROUND: This in-vitro investigation was designed to compare the flexural bond
      strengths of three commercially available ultra low fusing ceramic systems to
      Grade II Titanium and evaluate the type of bond failure through Scanning Electron
      Microscopy (SEM) and Energy Dispersion X ray Spectrum (EDS). MATERIALS & METHODS:
      Sixty patterns of auto polymerizing resin of dimensions 25.1 mm X 3.1mm X 0.6mm
      each were fabricated from a stainless steel die. Titanium casting for all the
      samples was done in a Titanium casting machine. Ten samples were allotted to each
      of three groups randomly. Ceramic build up was done step by step using the
      manufacturers' instructions. Flexural Bond strength tests for the samples were
      performed by using a 3-point bending test on a Universal testing machine in
      compliance with Deutsches Institut fur Normung (DIN) 13.927 draft. After the
      tests were completed, three samples, one from each group were selected randomly
      for the subsequent Scanning Electronic Microscopy (SEM) studies to characterize
      the type and morphology of the fracture in representative specimens. RESULTS: The
      maximum load to fracture the porcelain was recorded for each specimen. All the
      means of the three groups were compared by one-way Analysis of Variance (ANOVA)
      and it was found that Group I & Group III had significantly higher bond strength
      values as compared with the Group II (P< 0.001). All the 10 samples of Group I &
      III gave bond strength values above the standard values of 25 MPa. There was
      statistically significant difference in the bond strengths between Group I &
      Group III (t = 2.76 and P< 0.05), between Group I & II (t = 5.09 and P< 0.001)
      and between Group II & Group III (t = 13.28 and P< 0.001). SEM studies revealed
      occurrence of cohesive type fractures in the ceramic body of samples belonging to
      Groups I & III, while there was adhesive failure at ceramo-metal junction of
      samples belonging to Group II. EDS Analysis supported the findings of SEM
      studies. CONCLUSION: All the three ceramic systems fared better than the minimal
      recommended values stated by ISO 9693:1999 of 25MPa of which Orotig TiKrom was
      rated the best with values of 54.69 MPa. Vita TitanKeramik ranked second with
      values of 45.12MPa and the least values were obtained with Noritake Ti-22 with
      values of 27.76. The bond failure was predominantly cohesive in nature in case of
      Vita TitanKeramik and Orotig TiKrom; whereas adhesive failure was noticed in case
      of Noritake Ti-22. How to cite this article: Mabrurkar V, Habbu N, Hashmi SW,
      Musani S, Joshi N. In-vitro investigation to evaluate the flexural bond strengths
      of three commercially available ultra low fusing ceramic systems to Grade II
      Titanium. J Int Oral Health 2013;5(5):101-7.

PMID- 24324313
TI  - An in-vitro Evaluation of canal transportation and centering ability of two
      rotary Nickel Titanium systems (Twisted Files and Hyflex files) with conventional
      stainless Steel hand K-flexofiles by using Spiral Computed Tomography.
AB  - BACKGROUND: The purpose of this in-vitro study was to compare canal
      transportation and centering ability of Twisted and Hyflex Rotary Files with
      stainless steel hand k-flexofiles by using Spiral Computed Tomography. MATERIALS
      & METHODS: A total of 90 freshly extracted human mandibular single rooted
      Premolar teeth were selected. The crowns were flattened with steel disks and a
      final dimension of 18-mm WL was achieved for each tooth. Canals were divided
      randomly into 3 groups of 30 teeth each. Group I:Hyflex files, Group II:Twisted
      files, Group III:stainless steel hand k-flexofiles. Three sections from apical,
      mid-root, and coronal levels of the canal were recorded. All the teeth were
      scanned before and after instrumentation by using Spiral Computed Tomography.
      RESULTS: K-files showed highest transportation and less centered when compared to
      the Twisted and Hyflex rotary files. No significant difference was found between
      TF and Hyflex CM instruments. CONCLUSION: TF and Hyflex files shaped curved root
      canals without significant shaping errors when compared to the Hand stainless
      steel k-flexofiles. How to cite this article: Kumar BS, Pattanshetty S, Prasad M,
      Soni S, Pattanshetty KS, Prasad S. An in-vitro Evaluation of canal transportation
      and centering ability of two rotary Nickel Titanium systems (Twisted Files and
      Hyflex files) with conventional stainless Steel hand K-flexofiles by using Spiral
      Computed Tomography. J Int Oral Health 2013;5(5):108-15.

PMID- 24324314
TI  - Hollowbulb obturator with cast retainers: a case report.
AB  - One of the most rapidly growing areas of dentistry from the stand point of both
      interest and need is maxillofacial prosthetics. The research of cancer has made
      understanding and treatment of this dreadful disease a possibility. Still the
      rehabilitation of these patients is a daunting job. The factors which determine
      the prognosis of prosthetic reconstruction are size of the defect, ability of the
      hard and soft tissues in defect area, proximity of vital structures, systemic
      conditions and the most important of all, patients attitude and temperament. This
      article presents case of a hemimaxillectomy patient, where rehabilitation is
      carried out with a simple hollow bulb obturator, which is light in weight and
      aids in better retention and comfort of the patient. How to cite this article:
      Manikanatan NS, Balakrishnan D. Hollowbulb Obturator with Cast Retainers: A Case
      Report. J Int Oral Health 2013; 5(5):116-9. 

PMID- 24324315
TI  - A Simple and Cost Effective Method used for Removal of a Fractured Implant
      Abutment Screw: A Case Report.
AB  - The success of dental implants is based primarily on the extent of
      osseointegration. The failure of dental implants is not only due to biological
      factors, such as unsuccessful osseointegration or the presence of peri
      implantitis, but may also result from technical complications. Fracture of the
      implant abutment screw can be a serious problem, as the fragment remaining inside
      the implant may prevent the implant from functioning efficiently as an anchor. A
      simple and cost effective procedure used for the removal of fractured screw
      fragments and the successful utilization of the existing prosthesis are described
      in this clinical report. How to cite this article: Satwalekar P, Chander KS,
      Reddy BA, Sandeep N, Sandeep N, Satwalekar T. A Simple and Cost Effective Method
      used for Removal of a Fractured Implant Abutment Screw: A Case Report. J Int Oral
      Health 2013; 5(5):120-3. 

PMID- 24324316
TI  - A rare case of extrafollicular adenomatoid odontogenic tumour in the posterior
      region of the mandible: misdiagnosed as residual cyst.
AB  - Adenomatoid odontogenic tumor is a relatively uncommon distinct odontogenic
      neoplasm. It is an uncommon tumor of odontogenic origin with varying number of
      ductlike structures and inductive changes in the stroma. It is a benign and slow
      growing epithelial tumor and represents 3% of all odontogenic tumors. Its
      occurrence is more common in anterior region of the maxilla than mandible. Most
      of the adenomatoid odontogenic tumors occur intra-osseously but few peripheral
      variant have been reported which are attached to the gingival structures. The
      intra-osseous Adenomatoid odontogenic tumor may be related to unerrupted tooth
      (follicular varient) or may not (extrafollicular varient) be related to
      unerrupted tooth. This paper is to present a rare case of an extrafollicular
      Adenomatoid odontogenic tumor occurring in the body of the mandible in a male
      patient which is distinct and secondly it was clinically and radiographically
      diagnosed as residual cyst. The diagnosis of Adenomatoid odontogenic tumor was
      confirmed by Histopathological investigation. How to cite this article: Shivali
      V, Khanna VD, Khanna P, Singh A, Pandey A, Ahuja T. A Rare Case of
      Extrafollicular Adenomatoid Odontogenic Tumour in the Posterior Region of the
      Mandible: Misdiagnosed as Residual Cyst. J Int Oral Health 2013; 5(5):124-8. 

PMID- 24324317
TI  - Rehabilitation of complicated crown-root fracture by fragment reattachment and
      intraradicular splinting: case reports.
AB  - This paper describes the rehabilitation of two traumatised teeth in two patients
      namely; A maxillary left central incisor with a relatively rare combination of
      multiple fractures- uncomplicated crown fracture, complicated crown-root fracture
      along with an oblique fracture in middle third of the root and A traumatised
      mandibular central incisor with a horizontal fracture in cervical third of the
      root and complete separation of the fragments. In both cases, initially the
      fractured crown fragments were extracted which was followed by pulpectomy and
      placement of fiber posts luted with resin cement. The fractured fragments were
      then reattached to the respective teeth using resin cement. In the first case,
      the fractured incisal edge of the fragment was built up with a hybrid composite.
      Teeth were splinted with fibre splint (Ribbond) in both the cases. The patient
      was recalled regularly for follow ups for six months in first case. The patient
      presented with normal clinical and radiographic findings at each visit. In the
      second case, follow ups were carried out for 3 weeks and being continued and both
      the cases are still under observation by regular recalls. How to cite this
      article: Ruchi Arora, B Shivakumar, H Murali Rao, R Vijay. Rehabilitation of
      Complicated Crown-Root Fracture by Fragment Reattachment and Intraradicular
      Splinting: Case Reports. J Int Oral Health 2013; 5(5):129-38. 

PMID- 24324318
TI  - Oral findings in a patient with Sebaceous Nevi - A Case Report.
AB  - The presentation herewith as scripted is to describe a case with Nevus sebaceous
      with oral manifestations. Nevus Sebaceous or Jadassohn's nevus is an epidermal
      nevus with predominant sebaceous glands seen histologically. Reports of oral
      involvement have been few ranging from papillomatous growths of the tongue,
      gingiva, palate to dental abnormalities such as anodontia and dysodontia. The
      present case describes a nevus sebaceous present on the right half of the face
      and neck, showing intraoral papillomatous growth on the lateral part of the
      tongue on the right side. The patient was healthy and did not report involvement
      of any other organ systems. Intraoral involvement may be seen in patients with
      Nevus Sebaceous, hence proper screening is important. In patients presenting with
      large nevi on the head and neck such as ours, involvement of other systems such
      as ocular, neurologic and oral lesions may be seen, therefore screening of such
      patients is of importance. Patients with nevus sebaceous may be predisposed to
      the occurrence of tumours. Therefore, careful screening of such patients is
      necessary. How to cite this article: Baliga V, Gopinath VP, Baliga S, Chandra U.
      Oral findings in a patient with Sebaceous Nevi - A Case Report. J Int Oral Health
      2013; 5(5):139-42. 

PMID- 24324319
TI  - No carious cervical lesions: abfraction.
AB  - Abfraction or Theory of Abfraction is a theory explaining the non-carious
      cervical lesions (NCCL). It suggests that they are caused by flexural forces,
      usually from cyclic loading; the enamel, especially at the cementoenamel junction
      (CEJ), undergoes this pattern of destruction by separating the enamel rods.
      Clinical aspect importance of these ineart lesions are at most important to be
      detected for early intervention and treatment modalities as options during the
      progression of the disease. How to cite this article: Shetty SM, Shetty RG,
      Mattigatti S, Managoli NA, Rairam SG, Patil AM. No Carious Cervical Lesions:
      Abfraction. J Int Oral Health 2013; 5(5):142-5. 

PMID- 24324320
TI  - A foreigner in squamous cell carcinoma!
AB  - Giant cells are the soldiers of defensive system of our body. They differ based
      on the stimuli that provoked their formation. On the other hand, squamous cell
      carcinoma (SCC) being the most common oral cancer, presents with varied
      histopathological features based on the degree of differentiation. Keratinizing
      islands of dysplastic squamous epithelial cells & a dense inflammatory response
      form the major component of well differentiated SCC. This keratin component may
      sometimes trigger foreign body giant cell (FBGC) reaction in the stroma, which
      may mislead the pathologist to aggressive forms of SCC containing pleomorphic
      giant cells. We encountered such an interesting case of foreign body giant cell
      reaction in oral SCC. Thus, the present article aims to provide a thorough
      knowledge on FBGC including their appearance, pathogenesis & significance in oral
      SCC. How to cite this article: Patil S, Rao RS, Ganavi BS. A Foreigner in
      Squamous Cell Carcinoma!. J Int Oral Health 2013;5(5):147-50. 

PMID- 24324321
TI  - Optimal phase response functions for fast pulse-coupled synchronization in
      wireless sensor networks.
AB  - Synchronization is crucial to wireless sensor networks. Recently a pulse-coupled
      synchronization strategy that emulates biological pulse-coupled agents has been
      used to achieve this goal. We propose to optimize the phase response function
      such that synchronization rate is maximized. Since the synchronization rate is
      increased independently of transmission power, energy consumption is reduced,
      hence extending the life of battery-powered sensor networks. Comparison with
      existing phase response functions confirms the effectiveness of the method.

PMID- 24324322
TI  - Statistical analysis of the pulse-coupled synchronization strategy for wireless
      sensor networks.
AB  - Pulse-coupled synchronization is attracting increased attention in the sensor
      network community. Yet its properties have not been fully investigated. Using
      statistical analysis, we prove analytically that by controlling the number of
      connections at each node, synchronization can be guaranteed for generally pulse
      coupled oscillators even in the presence of a refractory period. The approach
      does not require the initial phases to reside in half an oscillation cycle, which
      improves existing results. We also find that a refractory period can be
      strategically included to reduce idle listening at nearly no sacrifice to the
      synchronization probability. Given that reduced idle listening leads to higher
      energy efficiency in the synchronization process, the strategically added
      refractory period makes the synchronization scheme appealing to cheap sensor
      nodes, where energy is a precious system resource. We also analyzed the pulse
      coupled synchronization in the presence of unreliable communication links and
      obtained similar results. QualNet experimental results are given to confirm the
      effectiveness of the theoretical predictions.

PMID- 24324323
TI  - Computational Identification of MicroRNAs from the Expressed Sequence Tags of
      Toxic Dinoflagellate Alexandrium Tamarense.
AB  - Micro ribonucleic acids (miRNAs) represent a class of small noncoding RNAs that
      play important roles in multiple biological processes by degrading targeted mRNAs
      or by repressing mRNA translation. In the case of algal lineages, especially
      dinoflagellates, knowledge regarding the miRNA system is still limited and its
      regulatory role remains unclear. In the present study, a computational approach
      was employed to screen miRNAs from the expressed sequence tags (ESTs) of
      Alexandrium tamarense. A total of 18 potential miRNAs were identified according
      to a range of filtering criteria. In addition, unique evolutionary features, such
      as miRNA gene duplication and sequence similarity to metazoan miRNAs, implied
      that the miRNA system in dinoflagellates is complex. Moreover, based on these 18
      miRNA sequences, 42 potential target genes showing diverse functions in
      regulating growth and development were predicted in Thalassiosira pseudonana and
      Phaeodactylum tricornutum. Taken together, our data suggest the existence of
      miRNAs in dinoflagellates and provide clues for further functional studies on
      these predicted miRNAs. 

PMID- 24324324
TI  - EASER: Ensembl Easy Sequence Retriever.
AB  - The rapid advances in genome sequencing technologies have increased the pace at
      which biological sequence databases are becoming available to the broad
      scientific community. Thus, obtaining and preparing an appropriate sequence
      dataset is a crucial first step for all types of genomic analyses. Here, we
      present a script that can widely facilitate the easy, fast, and effortless
      downloading and preparation of a proper biological sequence dataset for various
      genomics studies. This script retrieves Ensembl defined genomic features,
      associated with a given Ensembl identifier. Coding (CDS) and genomic sequences
      can be easily retrieved based on a selected relationship from a set of
      relationship types, either considering all available organisms or a user
      specified subset of organisms. The script is very user-friendly and by default
      starts with an interactive mode if no command-line options are specified. 

PMID- 24324325
TI  - Are the somatic mutation and tissue organization field theories of carcinogenesis
      incompatible?
AB  - Two drastically different approaches to understanding the forces driving
      carcinogenesis have crystallized through years of research. These are the somatic
      mutation theory (SMT) and the tissue organization field theory (TOFT). The
      essence of SMT is that cancer is derived from a single somatic cell that has
      successively accumulated multiple DNA mutations, and that those mutations occur
      on genes which control cell proliferation and cell cycle. Thus, according to SMT,
      neoplastic lesions are the results of DNA-level events. Conversely, according to
      TOFT, carcinogenesis is primarily a problem of tissue organization: carcinogenic
      agents destroy the normal tissue architecture thus disrupting cell-to-cell
      signaling and compromising genomic integrity. Hence, in TOFT the DNA mutations
      are the effect, and not the cause, of the tissue-level events. Cardinal
      importance of successful resolution of the TOFT versus SMT controversy dwells in
      the fact that, according to SMT, cancer is a unidirectional and mostly
      irreversible disease; whereas, according to TOFT, it is curable and reversible.
      In this paper, our goal is to outline a plausible scenario in which TOFT and SMT
      can be reconciled using the framework and concepts of the self-organized
      criticality (SOC), the principle proven to be extremely fruitful in a wide range
      of disciplines pertaining to natural phenomena, to biological communities, to
      large-scale social developments, to technological networks, and to many other
      subjects of research. 

PMID- 24324327
TI  - Effects of 6 months of abatacept treatment on aortic stiffness in patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Systemic inflammation plays an important role in the increased
      cardiac risk observed in rheumatoid arthritis (RA). Effective control of
      inflammation and disease activity may be of benefit in reducing cardiovascular
      risk in RA patients. OBJECTIVE: Our study was conducted in patients with active
      RA to investigate the effects of 24-week abatacept treatment on aortic stiffness
      measured by pulse wave velocity (PWV). RESULTS: The study included 21 patients,
      of whom 17 were females, with a mean age of 65.2+/-13.7 years. Ten patients had
      positive rheumatoid factors, 16 positive anti-citrullinated protein antibodies,
      and 19 presented an erosive form of RA. Sixteen patients were nonresponders to
      anti-tumor necrosis factor-alpha treatments. After 6 months of abatacept
      treatment, there was a significant increase in PWV levels (9.8+/-2.9 versus 8.5+/
      3.9 m/second; P=0.02). A nonsignificant increase in total cholesterol and low
      density lipoprotein cholesterol was observed. There was also a significant
      increase in high-density lipoprotein cholesterol levels, which led to a
      nonsignificant decrease in atherogenic index. The improvement in disease activity
      was significant, and there was a decrease of systemic inflammatory parameters,
      but without reaching statistical significancy. Changes in PWV were significantly
      correlated with changes in Disease Activity Score on 28 joints based on
      erythrocyte sedimentation rate (r=0.46; P=0.035) and in high-density lipoprotein
      cholesterol (r=-0.38; P=0.046). No correlation was observed with changes in C
      reactive protein and in other parameters of lipid profile or in steroid dose.
      CONCLUSION: The worsening of aortic stiffness found after 6 months of abatacept
      therapy might be due to an insufficient decrease in systemic inflammation.

PMID- 24324326
TI  - Optimizing therapeutics in the management of patients with multiple sclerosis: a
      review of drug efficacy, dosing, and mechanisms of action.
AB  - Multiple sclerosis (MS) is a debilitating neurological disorder that affects
      nearly 2 million adults, mostly in the prime of their youth. An environmental
      trigger, such as a viral infection, is hypothesized to initiate the abnormal
      behavior of host immune cells: to attack and damage the myelin sheath surrounding
      the neurons of the central nervous system. While several other pathways and
      disease triggers are still being investigated, it is nonetheless clear that MS is
      a heterogeneous disease with multifactorial etiologies that works independently
      or synergistically to initiate the aberrant immune responses to myelin. Although
      there are still no definitive markers to diagnose the disease or to cure the
      disease per se, research on management of MS has improved many fold over the past
      decade. New disease-modifying therapeutics are poised to decrease immune
      inflammatory responses and consequently decelerate the progression of MS disease
      activity, reduce the exacerbations of MS symptoms, and stabilize the physical and
      mental status of individuals. In this review, we describe the mechanism of
      action, optimal dosing, drug administration, safety, and efficacy of the disease
      modifying therapeutics that are currently approved for MS therapy. We also
      briefly touch upon the new drugs currently under investigation, and discuss the
      future of MS therapeutics. 

PMID- 24324328
TI  - Estrogen receptor modulatory effects of germinated brown rice bioactives in the
      uterus of rats through the regulation of estrogen-induced genes.
AB  - PURPOSE: The expression of genes regulated by estrogen in the uterus was studied
      in ovariectomized (OVX) rats treated with germinated brown rice (GBR) bioactives,
      and compared to Remifemin or estrogen at different doses to identify the
      regulation of these genes in the uterus and their molecular mechanisms. METHODS:
      Rats were treated orally with GBR bioactives (phenolics), acylated steryl
      glucosides (ASG), gamma-amino butyric acid (GABA), and gamma-oryzanol (ORZ) at
      100 and 200 mg/kg, Remifemin (REM) at 10 mg/kg and 20 mg/kg, or estrogen (EST) at
      0.2 mg/kg. Ribonucleic acid (RNA) was extracted from the uterus, and messenger
      (m)RNA expression of selected genes encoding estrogen receptor-beta (ER-beta),
      calcium-binding protein (CaBP9k), complement protein (C3), heat shock protein 70
      kDa (HSP70), and interleukin (IL)-4 receptor were quantified. Similarly, serum
      steroid hormone concentration was monitored at 2, 4, and 8 weeks after
      treatments. ER-beta antibody binding to the uterus sections was also studied
      using immunohistochemistry. RESULTS: The group treated with EST (0.2 mg/kg)
      upregulated ER-beta, C3, and IL-4 receptor genes compared to other groups
      (P<0.001). GBR phenolics (200 mg/kg) treatment upregulated the ER-beta gene
      almost to the level of the sham non-treated group. The CaBP9k gene showed
      upregulation in groups treated with ASG (200 mg/kg), EST (0.2 mg/kg), and ORZ
      (200 mg/kg) (P<0.05). Estrogen levels increased in groups treated with EST, ASG,
      and ORZ (200 mg/kg) compared to the OVX untreated group (P<0.05), and there was a
      slight non-significant decrease (P>0.05) in the progesterone levels in the OVX
      untreated group compared to the sham and other treated groups. There was a
      significant increase at 8 weeks in the level of FSH (P<0.05) in the treated
      groups compared to the OVX untreated group. There was no significant difference
      (P>0.05) in serum luteinizing hormone (LH) between the OVX untreated group and
      other groups. The sham and GBR phenolics treated group showed ER-beta reactivity
      at the glandular epithelium, while the group treated with EST showed
      immunoreactivity at the glandular, luminal, and stromal epithelium. CONCLUSION:
      GBR phenolics moderately regulate the expression of ER-beta, HSP70, and IL-4
      receptor genes, and gave a positive immunoreaction to ER-beta antigen in the
      uterus. ASG regulates the expression of CaBP9k and IL-4 receptor genes, and ORZ
      regulates the expression of the CaBP9k gene, while GABA at 100 mg/kg regulates
      the expression of the HSP70 gene. GBR and its bioactives might have an effect on
      estrogen-regulated genes in the uterus of rats.

PMID- 24324329
TI  - A computational assay to design an epitope-based Peptide vaccine against saint
      louis encephalitis virus.
AB  - Saint Louis encephalitis virus, a member of the flaviviridae subgroup, is a culex
      mosquito-borne pathogen. Despite severe epidemic outbreaks on several occasions,
      not much progress has been made with regard to an epitope-based vaccine designed
      for Saint Louis encephalitis virus. The envelope proteins were collected from a
      protein database and analyzed with an in silico tool to identify the most
      immunogenic protein. The protein was then verified through several parameters to
      predict the T-cell and B-cell epitopes. Both T-cell and B-cell immunity were
      assessed to determine that the protein can induce humoral as well as cell
      mediated immunity. The peptide sequence from 330-336 amino acids and the sequence
      REYCYEATL from the position 57 were found as the most potential B-cell and T-cell
      epitopes, respectively. Furthermore, as an RNA virus, one important thing was to
      establish the epitope as a conserved one; this was also done by in silico tools,
      showing 63.51% conservancy. The epitope was further tested for binding against
      the HLA molecule by computational docking techniques to verify the binding cleft
      epitope interaction. However, this is a preliminary study of designing an epitope
      based peptide vaccine against Saint Louis encephalitis virus; the results awaits
      validation by in vitro and in vivo experiments. 

PMID- 24324330
TI  - ChIP-Seq Data Mining: Remarkable Differences in NRSF/REST Target Genes between
      Human ESC and ESC-Derived Neurons.
AB  - The neuron-restrictive silencer factor (NRSF) is a zinc finger transcription
      factor that represses neuronal gene transcription in non-neuronal cells by
      binding to the consensus repressor element-1 (RE1) located in regulatory regions
      of target genes. NRSF silences the expression of a wide range of target genes
      involved in neuron-specific functions. Previous studies showed that aberrant
      regulation of NRSF plays a key role in the pathological process of human
      neurodegenerative diseases. However, a comprehensive set of NRSF target genes
      relevant to human neuronal functions has not yet been characterized. We performed
      genome-wide data mining from chromatin immunoprecipitation followed by deep
      sequencing (ChIP-Seq) datasets of NRSF binding sites in human embryonic stem
      cells (ESC) and the corresponding ESC-derived neurons, retrieved from the
      database of the ENCODE/HAIB project. Using bioinformatics tools such as Avadis
      NGS and MACS, we identified 2,172 NRSF target genes in ESC and 308 genes in ESC
      derived neurons based on stringent criteria. Only 40 NRSF target genes overlapped
      between both data sets. According to motif analysis, binding regions showed an
      enrichment of the consensus RE1 sites in ESC, whereas they were mainly located in
      poorly defined non-RE1 sites in ESC-derived neurons. Molecular pathways of NRSF
      target genes were linked with various neuronal functions in ESC, such as
      neuroactive ligand-receptor interaction, CREB signaling, and axonal guidance
      signaling, while they were not directed to neuron-specific functions in ESC
      derived neurons. Remarkable differences in ChIP-Seq-based NRSF target genes and
      pathways between ESC and ESC-derived neurons suggested that NRSF-mediated
      silencing of target genes is highly effective in human ESC but not in ESC-derived
      neurons. 

PMID- 24324331
TI  - Effectiveness of a lifestyle exercise program for older people receiving a
      restorative home care service: a pragmatic randomized controlled trial.
AB  - BACKGROUND: Restorative home care services are short-term and aimed at maximizing
      a person's ability to live independently. They are multidimensional and often
      include an exercise program to improve strength, mobility, and balance. The aim
      of this study was to determine whether a lifestyle exercise program would be
      undertaken more often and result in greater functional gains than the current
      structured exercise program delivered as part of a restorative home care service
      for older adults. METHODS: A pragmatic randomized controlled trial was conducted
      in an organization with an established restorative home care service. Individuals
      who were to have an exercise program as part of their service were randomized to
      receive either a lifestyle and functional exercise program called LiFE (as this
      was a new program, the intervention) or the structured exercise program currently
      being used in the service (control). Exercise data collected by the individuals
      throughout and pre and post intervention testing was used to measure balance,
      strength, mobility, falls efficacy, vitality, function, and disability. RESULTS:
      There was no difference between the groups in the amounts of exercise undertaken
      during the 8-week intervention period. Outcome measurement indicated that the
      LiFE program was as effective, and on 40% of the measures, more effective, than
      the structured exercise program. CONCLUSION: Organizations delivering restorative
      home care services that include an exercise component should consider whether
      LiFE rather than the exercise program they are currently using could help their
      clients achieve better outcomes.

PMID- 24324332
TI  - Relation between the ankle-brachial index and the complexity of coronary artery
      disease in older patients.
AB  - BACKGROUND: In the elderly, the ankle-brachial index (ABI) has greater than 90%
      sensitivity and specificity for peripheral artery disease identification. A well
      known relation exists between peripheral artery disease and the number of
      diseased coronary vessels. Yet, other anatomical characteristics have important
      impacts on the type of treatment and prognosis. PURPOSE: To determine the
      relation between ABI and the complexity of coronary artery disease, by different
      anatomical classifications. METHODS: This study was a prospective analysis of
      patients >=65 years old who were undergoing elective coronary angiography for
      ischemic coronary disease. The ABI was calculated for each leg, as the ratio
      between the lowest ankle pressure and the highest brachial pressure. The analysis
      of coronary anatomy was performed by three interventional cardiologists; it
      included classification of each lesion with >50% diameter stenosis, according to
      the American Heart Association criteria, and calculation of the SYNTAX score.
      RESULTS: The study recruited 204 consecutive patients (median age: 72.5 years).
      Stable angina was present in 51% of patients. Although only 1% of patients
      reported peripheral artery disease, 45% exhibited an abnormal ABI. The number of
      lesions per patient, the number of patients with complex lesions, and the median
      SYNTAX scores were greater in the group with abnormal ABI. However, among 144
      patients with obstructive coronary artery disease, despite abnormal ABI being
      able to identify a higher rate of patients with B2 or C type lesions (70.9%
      versus 53.8%; P=0.039), the mean SYNTAX scores (13 versus 9; P=0.14), and the
      proportion of patients with SYNTAX score >16 (34.2% versus 27.7%; P=0.47), were
      similar, irrespective of ABI. CONCLUSION: In patients >=65 years old the presence
      of peripheral artery disease could discriminate a group of patients with greater
      occurrence of B2 and C type lesions, but similar median SYNTAX score.

PMID- 24324333
TI  - Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and
      hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in
      vitro.
AB  - OBJECTIVE: To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L
      lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the
      photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular
      carcinoma HepG2 cells and to investigate potential apoptotic mechanisms. METHODS:
      PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA
      DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME
      (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The
      cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA
      against HepG2 cells was measured, and the cellular reactive oxygen species,
      percentage of cells with mitochondrial membrane potential depolarization, and
      apoptotic rate following treatment were determined. RESULTS: Four nanovesicles
      (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA) were
      synthesized, and mean particle sizes were 175+/-18 nm, 154+/-3 nm, 196+/-2 nm,
      and 147+/-15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG
      PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the
      highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated
      cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar
      fluorescence intensity. Mitochondrial membrane potential depolarization was
      observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with PEG-PDLLA
      DOX-HMME, PEG-PDLLA-HMME, PEG-PDLLA-DOX, and PEG-PDLLA, respectively. The
      apoptotic rate was significantly higher in PEG-PDLLA-DOX-HMME-treated cells
      compared with PEG-PDLLA-DOX- and PEG-PDLLA-HMME-treated cells. CONCLUSION: The
      PEG-PDLLA nanovesicle, a drug delivery carrier, can be simultaneously loaded with
      two anticancer drugs (hydrophilic DOX and hydrophobic HMME). PEG-PDLLA-DOX-HMME
      cytotoxicity to HepG2 cells is significantly higher than the PEG-PDLLA
      nanovesicle loaded with DOX or HMME alone, and DOX and HMME have a synergistic
      effect against human hepatocellular carcinoma HepG2 cells.

PMID- 24324334
TI  - Evaluation of glycophenotype in breast cancer by quantum dot-lectin
      histochemistry.
AB  - Cell surface glycoconjugates play an important role in
      differentiation/dedifferentiation processes and lectins are employed to evaluate
      them by several methodologies. Fluorescent probes are considered a valuable tool
      because of their ability to provide a particular view, and are more detailed and
      sensitive in terms of cell structure and molecular content. The aim of this study
      was to evaluate and compare the expression and distribution of glycoconjugates in
      normal human breast tissue, and benign (fibroadenoma), and malignantly
      transformed (invasive ductal carcinoma) breast tissues. For this, we used
      mercaptosuccinic acid-coated Cadmium Telluride (CdTe) quantum dots (QDs)
      conjugated with concanavalin A (Con A) or Ulex europaeus agglutinin I (UEA I)
      lectins to detect alpha-D-glucose/mannose and L-fucose residues, respectively.
      The QD-lectin conjugates were evaluated by hemagglutination activity tests and
      carbohydrate inhibition assays, and were found to remain functional, keeping
      their fluorescent properties and carbohydrate recognition ability. Fluorescence
      images showed that different regions of breast tissue expressed particular types
      of carbohydrates. While the stroma was preferentially and intensely stained by QD
      Con A, ductal cells were preferentially labeled by QD-UEA I. These results
      indicate that QD-lectin conjugates can be used as molecular probes and can help
      to elucidate the glycoconjugate profile in biological processes. 

PMID- 24324336
TI  - Fascination and Social Togetherness-Discussions about Spice Smoking on a Swedish
      Internet Forum.
AB  - Spice is a smoking mixture containing synthetic cannabinoids with psychoactive
      effects similar to herbal cannabis. It is sold on the Internet and has become
      popular among young people. The purpose of the present study was to investigate
      experiences of intoxication induced by Spice, as described on a Swedish internet
      based discussion forum. A systematic search yielded 40 reports, which were
      analyzed using phenomenological method. A total of 7 themes (composed of 27
      categories) emerged from the analysis: 1. Spice use as social ritual; 2. Social
      secretiveness; 3. Intoxication remarks; 4. Well-being and elation; 5. Altered
      perception of reality; 6. Fears and coping; 7. Unpleasant physical effects. The
      results show that smoking was a social activity mostly carried out in small peer
      groups, and that the substances induced strong intoxication with both positive
      and negative effects. Despite fears and unpleasant effects, the intoxication was
      often considered fascinating and rewarding. 

PMID- 24324335
TI  - Current clinical application of deep-brain stimulation for essential tremor.
AB  - BACKGROUND: Deep-brain stimulation (DBS) is an established treatment for
      medically refractory essential tremor (ET). This article reviews the current
      evidence supporting the efficacy and safety of DBS targets, including the ventral
      intermediate (VIM) nucleus and posterior subthalamic area (PSA) in treatment of
      ET. METHODS: A structured PubMed search was performed through December 2012 with
      keywords "deep brain stimulation (DBS)," "essential tremor (ET)," "ventral
      intermediate (VIM) nucleus," "posterior subthalamic area (PSA)," "safety," and
      "efficacy." RESULTS: Based on level IV evidence, both VIM and PSA DBS targets
      appear to be safe and efficacious in ET patients in tremor reduction and
      improving activities of daily living, though the literature on PSA DBS is limited
      in terms of bilateral stimulation and long-term follow-up. DBS-related adverse
      effects are typically mild and stimulation-related. Hardware-related
      complications after DBS may not be uncommon, and often require additional
      surgical procedures. Few studies assessed quality-of-life and cognition outcomes
      in ET patients undergoing DBS stimulation. CONCLUSION: DBS appears to be a safe
      and effective treatment for medically refractory ET. More systematic studies
      comparing VIM and PSA targets are needed to ascertain the most safe and effective
      DBS treatment for medically refractory ET. More research is warranted to assess
      quality-of-life and cognition outcomes in ET patients undergoing DBS.

PMID- 24324337
TI  - Role, implementation, and effectiveness of advanced allied health assistants: a
      systematic review.
AB  - BACKGROUND: The purpose of this systematic review was to determine the
      effectiveness and implementation of advanced allied health assistant roles.
      METHODS: A systematic search of seven databases and Google Scholar was conducted
      to identify studies published in English peer-reviewed journals from 2003 to 2013
      and reporting on the effectiveness and implementation of advanced allied health
      assistant (A/AHA) roles. Reference lists were also screened to identify
      additional studies, and the authors' personal collections of studies were
      searched. Studies were allocated to the National Health and Medical Research
      Council hierarchy of evidence, and appraisal of higher-level studies (III-1 and
      above) conducted using the Centre for Evidence Based Medicine Systematic Review
      Critical Appraisal Sheet for included systematic reviews or the PEDro scale for
      level II and III-1 studies. Data regarding country, A/AHA title, disciplines,
      competencies, tasks, level of autonomy, clients, training, and issues regarding
      the implementation of these roles were extracted, as were outcomes used and key
      findings for studies investigating their effectiveness. RESULTS: Fifty-three
      studies were included, and most because they reported background information
      rather than investigating A/AHA roles, this representing low-level information.
      A/AHAs work in a range of disciplines, with a variety of client groups, and in a
      number of different settings. Little was reported regarding the training
      available for A/AHAs. Four studies investigated the effectiveness of these roles,
      finding that they were generally well accepted by clients, and provided more
      therapy time. Issues in integrating these new roles into existing health systems
      were also reported. CONCLUSION: A/AHA roles are being implemented in a range of
      settings, and appear to be effective in terms of process measures and stakeholder
      perceptions. Few studies have investigated these roles, indicating a need for
      research to be conducted in this area to enable policy-makers to consider the
      value of these positions and how they can best be utilized.

PMID- 24324338
TI  - Vaccination against human papillomavirus among 865 female students from the
      health professions in central Greece: a questionnaire-based cross-sectional
      study.
AB  - BACKGROUND: There are still sparse data on vaccination coverage against human
      papillomavirus (HPV) among students in the health professions. The aim of this
      study was to investigate HPV vaccination coverage in female students from the
      health professions in Greece. METHODS: A self-administered, anonymous
      questionnaire was distributed to second-year and third-year female students
      pursuing degrees in medicine, nursing, and paramedical health disciplines in
      central Greece. RESULTS: Overall vaccination coverage was 44.3%. The major reason
      for lack of vaccination was fear about safety of the vaccine. Participants who
      had received information about safety of the vaccine from the mass media and
      paramedical students had lower vaccination coverage in comparison with students
      who had received information about vaccine safety from alternative sources.
      CONCLUSION: Further quantitative and qualitative research is needed to design
      educational activities targeting female students in the health professions in
      order to create a positive domino effect and improve HPV vaccination coverage
      levels in Greece.

PMID- 24324340
TI  - Environmental health hazardscapes.

PMID- 24324339
TI  - Quality improvement in clinical documentation: does clinical governance work?
AB  - INTRODUCTION: The quality of nursing documentation is still a challenge in the
      nursing profession and, thus, in the health care industry. One major quality
      improvement program is clinical governance, whose mission is to continuously
      improve the quality of patient care and overcome service quality problems. The
      aim of this study was to identify whether clinical governance improves the
      quality of nursing documentation. METHODS: A quasi-experimental method was used
      to show nursing documentation quality improvement after a 2-year clinical
      governance implementation. Two hundred twenty random nursing documents were
      assessed structurally and by content using a valid and reliable researcher made
      checklist. RESULTS: There were no differences between a nurse's demographic data
      before and after 2 years (P>0.05) and the nursing documentation score did not
      improve after a 2-year clinical governance program. CONCLUSION: Although some
      efforts were made to improve nursing documentation through clinical governance,
      these were not sufficient and more attempts are needed.

PMID- 24324341
TI  - Sustained elevation of kynurenic Acid in the cerebrospinal fluid of patients with
      herpes simplex virus type 1 encephalitis.
AB  - Herpes simplex virus (HSV) type 1 encephalitis (HSE) is a viral infectious
      disease with commonly occurring neurodegeneration and neurological/cognitive long
      term sequelae. Kynurenic acid (KYNA) is a neuroactive tryptophan metabolite,
      which is elevated in the cerebrospinal fluid (CSF) during viral infection as a
      result of immune activation. The aim of the study was to investigate the role of
      endogenous brain KYNA for the long-term outcome of the disease. CSF KYNA
      concentration was analyzed in 25 HSE patients along the course of the disease and
      compared with that of 25 age-matched healthy volunteers. Within 3 weeks of
      admission CSF KYNA of HSE patients was markedly elevated (median 33.6 nM)
      compared to healthy volunteers (median 1.45 nM). Following a decline observed
      after 1-2 months, levels of CSF KYNA were elevated more than 1 year after
      admission (median 3.4 nM range: 1-9 years). A negative correlation was found
      between initial CSF KYNA concentrations and severity of the long-term sequelae.
      This study show a marked elevation in CSF KYNA from patients with HSE, most
      pronounced during the acute phase of the disease and slowly declining along the
      recovery. We propose that brain KYNA might potentially protect against
      neurodegeneration while causing a long-lasting loss in cognitive function
      associated with the disease. 

PMID- 24324342
TI  - Sam68 is a novel marker for aggressive neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (NB) is the most common solid extracranial tumor in
      children. However, the molecular mechanism and progression of NB is largely
      unknown, and unfortunately, the prognosis is poor. Src-associated in mitosis with
      a molecular weight of 68 kDa (Sam68) is associated with carcinogenesis and
      neurogenesis. The present study aimed to investigate the clinical and prognostic
      significance of Sam68 in NB. METHODS: The expression of Sam68 in immortalized
      normal epithelial cells, NB cell lines, and in four cases of paired NB tissue and
      adjacent normal tissue from the same patient was examined using Western blotting,
      reverse transcription-polymerase chain reaction (PCR) and real-time reverse
      transcription-PCR. The proliferation of NB cells was determined by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore,
      Sam68 protein expression was analyzed in 90 NB cases characterized as
      clinicopathological using immunohistochemistry. Statistical analyses were applied
      to evaluate the diagnostic value and associations of Sam68 with clinical
      parameters. RESULTS: Western blotting and reverse transcription-PCR showed that
      the expression level of Sam68 was markedly higher in NB cell lines than in the
      immortalized normal epithelial cells at both messenger RNA and protein levels.
      The MTT assay revealed that Sam68 expression supported proliferation of NB cells.
      Sam68 expression levels were significantly up-regulated in tumor tissues in
      comparison to the matched adjacent normal tissues from the same patient. Sam68
      protein level was positively correlated with clinical stage (P<0.001), tumor
      histology (P<0.001), and distant metastasis (P=0.029). Patients with higher Sam68
      expression had shorter overall survival time, whereas those with lower tumor
      Sam68 expression had longer survival time. CONCLUSION: Our results suggest that
      Sam68 expression is associated with neuroblastoma progression and may represent a
      novel and valuable predictor for prognostic evaluation of neuroblastoma patients.

PMID- 24324343
TI  - Optical imaging of head and neck squamous cell carcinoma in vivo using arginine
      glycine-aspartic acid peptide conjugated near-infrared quantum dots.
AB  - Molecular imaging plays a key role in personalized medicine and tumor diagnosis.
      Quantum dots with near-infrared emission spectra demonstrate excellent tissue
      penetration and photostability, and have recently emerged as important tools for
      in vivo tumor imaging. Integrin alphavbeta3 has been shown to be highly and
      specifically expressed in endothelial cells of tumor angiogenic vessels in almost
      all types of tumors, and specifically binds to the peptide containing arginine
      glycine-aspartic acid (RGD). In this study, we conjugated RGD with quantum dots
      with emission wavelength of 800 nm (QD800) to generate QD800-RGD, and used it via
      intravenous injection as a probe to image tumors in nude mice bearing head and
      neck squamous cell carcinoma (HNSCC). Twelve hours after the injection, the mice
      were still alive and were sacrificed to isolate tumors and ten major organs for
      ex vivo analysis to localize the probe in these tissues. The results showed that
      QD800-RGD was specifically targeted to integrin alphavbeta3 in vitro and in vivo,
      producing clear tumor fluorescence images after the intravenous injection. The
      tumor-to-background ratio and size of tumor image were highest within 6 hours of
      the injection and declined significantly at 9 hours after the injection, but
      there was still a clearly visible tumor image at 12 hours. The greatest amount of
      QD800-RGD was found in liver and spleen, followed by tumor and lung, and a weak
      fluorescence signal was seen in tibia. No detectable signal of QD800-RGD was
      found in brain, heart, kidney, testis, stomach, or intestine. Our study
      demonstrated that using integrin alphavbeta3 as target, it is possible to use
      intravenously injected QD800-RGD to generate high quality images of HNSCC, and
      the technique offers great potential in the diagnosis and personalized therapy
      for HNSCC. 

PMID- 24324344
TI  - Antibiotic sensitivity pattern of uropathogens from pregnant women with urinary
      tract infection in Abakaliki, Nigeria.
AB  - BACKGROUND: Urinary tract infection (UTI) is a common bacterial infection during
      pregnancy and a significant cause of perinatal and maternal morbidity and
      mortality. The causative bacteria have remained virtually the same although with
      variations in individual prevalence. There has been an increasing resistance by
      these bacteria to the commonly available antibiotics. OBJECTIVES: To determine
      the prevalence of UTI, the common causative bacteria, and their antibiotic
      sensitivity pattern among pregnant women with UTI. METHODOLOGY: This is a
      descriptive study that was carried out at the Obstetrics Department of two
      tertiary institutions in Abakaliki, Ebonyi State, Nigeria (Federal Medical Center
      and Ebonyi State University Teaching Hospital) over a period of 12 months.
      Midstream urine specimens from selected pregnant women with clinical features of
      UTI were collected for microscopy, culture, and sensitivity. The results were
      analyzed with the 2008 Epi InfoTM software. RESULTS: A total of 542 pregnant
      women presented with symptoms of UTI and were recruited for the study over the
      study period. Of the 542 pregnant women, 252 (46.5%) had significant bacteriuria
      with positive urine culture and varying antibiotic sensitivity pattern. The
      prevalence of symptomatic UTI was 3%. Escherichia coli was the most common
      bacteria isolated with a percentage of 50.8%. Other isolated micro organisms
      included Stapylococcus aereus (52 cultures, 20.6%), Proteus mirabilis (24
      cultures, 9.5%), S. saprophyticus (18 cultures, 7.1%), Streptococcus spp. (14
      cultures, 5.6%), Citrobacter spp. (5 cultures, 2.0%), Klebsiella spp. (4
      cultures, 1.6%), Enterobacter spp. (4 cultures, 1.6%), and Pseudomonas spp. (3
      cultures, 1.2%). Levofloxacin had the highest overall antibiotic sensitivity of
      92.5%. Others with overall antibiotic sensitivity pattern greater than 50%
      included cefpodoxime (87.3%), ofloxacin (77.4%), ciprofloxacin (66.7%),
      ceftriaxone (66.7%), and gentamicin (50.8%). CONCLUSION: E. coli was the most
      common etiological agent of UTI in pregnancy with Enterococcus (Staphylococcus)
      gaining prominence. Cephalosporin and quinolones were shown to be very effective
      against the organisms causing UTI in these pregnant women.

PMID- 24324345
TI  - Epidemiology of "fragile skin": results from a survey of different skin types.
AB  - BACKGROUND: Epidemiologic information regarding the prevalence of "fragile skin"
      in different adult populations is currently limited. The objective of the current
      survey was to assess the occurrence of perceived "fragile skin" across different
      skin types in the general adult population. METHODS: Individuals aged 15-65 years
      from five representative geographic regions (France, Spain, Sweden, Japan, and
      the US) were interviewed and grouped into the following skin types: Caucasian
      North skin (n=1,218), Caucasian South skin (n=1,695), Asian skin (n=1,500), and
      Black skin (n=500). The main survey question was "In your opinion, do you have
      fragile skin?" Concepts relating to the nature and appearance of an individual's
      skin were also evaluated. RESULTS: A total of 4,913 individuals were interviewed.
      Subjects in the Caucasian North, Caucasian South, Asian, and Black skin type
      groups responded positively to the question "In your opinion, do you have fragile
      skin?" in the following proportions: 24.44%, 29.71%, 52.67%, and 42.20%,
      respectively. With the exception of individuals in the Black skin group, "fragile
      skin" was prevalent in significantly more women than men (P<0.0001). Compared
      with other age categories, the prevalence of "fragile skin" was significantly
      higher in individuals aged 15-34 years (P<0.0001), regardless of skin type. In
      general, individuals reporting "fragile skin" were 2-3-fold more likely to
      respond positively to a series of questions relating to the nature and appearance
      of their skin. The prevalence of "fragile skin" was also higher in individuals
      who experienced dermatosis (skin lesions of any type) in the previous 12 months.
      CONCLUSION: Whilst these findings need to be confirmed through objective
      evaluation, the current survey demonstrated that "fragile skin" is perceived to
      occur in a substantial proportion of individuals from any given country,
      particularly in the age range of 15-34 years, regardless of skin type.

PMID- 24324346
TI  - S100 calcium binding protein B as a biomarker of delirium duration in the
      intensive care unit - an exploratory analysis.
AB  - BACKGROUND: Currently, there are no valid and reliable biomarkers to identify
      delirious patients predisposed to longer delirium duration. We investigated the
      hypothesis that elevated S100 calcium binding protein B (S100beta) levels will be
      associated with longer delirium duration in critically ill patients. METHODS: A
      prospective observational cohort study was performed in the medical, surgical,
      and progressive intensive care units (ICUs) of a tertiary care, university
      affiliated, and urban hospital. Sixty-three delirious patients were selected for
      the analysis, with two samples of S100beta collected on days 1 and 8 of
      enrollment. The main outcome measure was delirium duration. Using the cutoff of
      <0.1 ng/mL and >=0.1 ng/mL as normal and abnormal levels of S100beta,
      respectively, on day 1 and day 8, four exposure groups were created: Group A,
      normal S100beta levels on day 1 and day 8; Group B, normal S100beta level on day
      1 and abnormal S100beta level on day 8; Group C, abnormal S100beta level on day 1
      and normal on day 8; and Group D, abnormal S100beta levels on both day 1 and day
      8. RESULTS: Patients with abnormal levels of S100beta showed a trend towards
      higher delirium duration (P=0.076); Group B (standard deviation) (7.0 [3.2]
      days), Group C (5.5 [6.3] days), and Group D (5.3 [6.0] days), compared to
      patients in Group A (3.5 [5.4] days). CONCLUSION: This preliminary investigation
      identified a potentially novel role for S100beta as a biomarker for delirium
      duration in critically ill patients. This finding may have important implications
      for refining future delirium management strategies in ICU patients.

PMID- 24324347
TI  - Diffusion-weighted imaging and diffusion-weighted whole-body imaging with
      background body signal suppression for characterizing esophageal cancer: a case
      report.
AB  - PURPOSE: Information on the extent or structure of esophageal cancer (ESC) is
      necessary for identifying whether the carcinoma is localized or resectable.
      Diffusion-weighted imaging (DWI) and diffusion-weighted whole-body imaging with
      background body signal suppression (DWIBS) are useful for this purpose. PATIENTS
      AND METHODS: One case of ESC with dysphagia presented at our hospital. Endoscopic
      examination revealed an elevated lesion with an ulcer, and stenosis was detected.
      DWI showed a high-intensity signal extending from the proximal to the distal ends
      of the carcinoma and extending to the tunica adventitia. A strong signal was also
      observed using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET).
      DWIBS clearly revealed ESC, and these findings, along with those from DWI,
      suggested that our case had stage-T3 ESC. FDG-PET did not reveal the detailed
      structure of the ESC. DWIBS, on the other hand, showed that the signal extended
      to the tunica adventitia and the lumen of the esophagus. CONCLUSION: These
      findings suggest that DWI and DWIBS are useful for the detection and assessment
      of ESC.

PMID- 24324349
TI  - Aphakia correction by injection of foldable intra ocular lens in the anterior
      chamber.
AB  - We assessed the outcomes of the use of anterior chamber foldable lens for
      unilateral aphakia correction at the University Teaching Hospital of Yaounde. In
      this retrospective, non-comparative, consecutive case series study, we reviewed
      the records of patients who underwent an operation for aphakia correction by the
      means of injection of an angular supported foldable lens between January 2009 and
      December 2011 in the University Teaching Hospital Yaounde. Student's paired t
      test was carried out to compare pre-operative and post-operative visual acuity
      (VA) and intraocular pressure (IOP). P-values less than 0.05 were considered
      statistically significant. Twenty-one patients were included in the study; twelve
      were male (57.1%) and nine were female (42.9%). The mean age was 55.38 +/- 17.67
      years (range 9-75 years). The mean follow-up duration was 5.95 +/- 3.14 months
      (range 2-12 months). The mean log-MAR visual acuity was 1.26 +/- 0.46 pre
      operatively and 0.78 +/- 0.57 post-operatively (P = 0.003). The change in
      intraocular pressure was not statistically significant. Complications included
      intraocular hypertension (over 21 mmHg) in 3 patients (14.3%) and macular edema,
      pupillar ovalization, and retinal detachment in one patient each. The results
      indicate that injection of an angular support foldable lens in the anterior
      chamber is a useful technique for the correction of aphakia in eyes without
      capsular support. More extended follow-up, however, and a larger series of
      patients are needed to ascertain the effectiveness and safety of this procedure. 

PMID- 24324348
TI  - Capsular contracture by silicone breast implants: possible causes,
      biocompatibility, and prophylactic strategies.
AB  - The most common implanted material in the human body consists of silicone. Breast
      augmentation and breast reconstruction using silicone-based implants are
      procedures frequently performed by reconstructive and aesthetic surgeons. A main
      complication of this procedure continues to be the development of capsular
      contracture (CC), displaying the result of a fibrotic foreign body reaction after
      the implantation of silicone. For many years, experimental and clinical trials
      have attempted to analyze the problem of its etiology, treatment, and
      prophylaxis. Different theories of CC formation are known; however, the reason
      why different individuals develop CC in days or a month, or only after years, is
      unknown. Therefore, we hypothesize that CC formation, might primarily be induced
      by immunological mechanisms along with other reasons. This article attempts to
      review CC formation, with special attention paid to immunological and
      inflammatory reasons, as well as actual prophylactic strategies. In this context,
      the word "biocompatibility" has been frequently used to describe the overall
      biological innocuousness of silicone in the respective studies, although without
      clear-cut definitions of this important feature. We have therefore developed a
      new five-point scale with distinct key points of biocompatibility. Hence, this
      article might provide the basis for ongoing discussion in this field to reduce
      single-publication definitions as well as increase the understanding of
      biocompatibility. 

PMID- 24324350
TI  - An Antibody-based Blood Test Utilizing a Panel of Biomarkers as a New Method for
      Improved Breast Cancer Diagnosis.
AB  - In order to develop a new tool for diagnosis of breast cancer based on
      autoantibodies against a panel of biomarkers, a clinical trial including blood
      samples from 507 subjects was conducted. All subjects showed a breast abnormality
      on exam or breast imaging and final biopsy pathology of either breast cancer
      patients or healthy controls. Using an enzyme-linked immunosorbent assay, the
      samples were tested for autoantibodies against a predetermined number of
      biomarkers in various models that were used to determine a diagnosis, which was
      compared to the clinical status. Our new assay achieved a sensitivity of 95.2%
      [CI = 92.8-96.8%] at a fixed specificity of 49.5%. Receiver-operator
      characteristic curve analysis showed an area under the curve of 80.1% [CI = 72.6
      87.6%]. These results suggest that a blood test which is based on models
      comprising several autoantibodies to specific biomarkers may be a new and novel
      tool for improving the diagnostic evaluation of breast cancer. 

PMID- 24324351
TI  - Monitoring Osteoarthritis: A Cross-sectional Survey in General Practice.
AB  - BACKGROUND: Despite being a highly prevalent chronic condition managed
      predominantly in primary care and unlike other chronic conditions, osteoarthritis
      (OA) care is delivered on an ad hoc basis rather than through routine structured
      review. Evidence suggests current levels of OA care are suboptimal, but little is
      known about what general practitioners' (GPs) consider important in OA care, and,
      thus, the scope to improve inconsistency or poor practice is, at present,
      limited. OBJECTIVES: We investigated GPs' views on and practice of monitoring OA.
      METHODS: This was a cross-sectional postal survey of 2500 practicing UK GPs
      randomly selected from the Binley's database. Respondents were asked if
      monitoring OA patients was important and how monitoring should be undertaken.
      RESULTS: Responses were received from 768 GPs of whom 70.8% were male and 89.5%
      were principals within their practices. Despite 55.4% (n = 405) indicating
      monitoring patients with OA was important and 78.3% (n = 596) considering GPs the
      appropriate professionals to monitor OA, only 15.2% (n = 114) did so routinely,
      and 45% (n = 337) did not monitor any OA patients at all. In total, 61.4% (n =
      463) reported that patients should self-monitor. Respondents favored monitoring
      physical function, pain, and analgesia use over monitoring measures of BMI, self
      management plans, and exercise advice. CONCLUSIONS: The majority of respondents
      felt that monitoring OA was important, but this was not reflected in their
      reported current practice. Much of what they favored for monitoring was in line
      with published guidance, suggesting provision of suboptimal care does not result
      from lack of knowledge and interventions to improve OA care must address barriers
      to GPs engaging in optimal care provision.

PMID- 24324352
TI  - Challenges of caring for an advanced chronic kidney disease patient with severe
      thrombocytopenia.
AB  - An autogenous arteriovenous fistula has been considered to be the optimal form of
      vascular access for hemodialysis (HD) in the field of nephrology. Nevertheless,
      the decision regarding the type of access, whether it be an arteriovenous
      fistula, an arteriovenous graft, or a central venous catheter, must still be
      individualized. In the present report, we describe the case of a female patient
      with advanced chronic kidney disease (CKD) associated with a hemostatic disorder.
      Despite the exhausted peripheral vasculature, she required recurrent platelet
      transfusions for severe thrombocytopenia due to aplastic anemia. The goal of care
      for this patient was to optimize the dialysis treatment without increasing the
      bleeding risk. Various concerns regarding the therapeutic conundrums encountered
      in the case are also discussed. 

PMID- 24324353
TI  - Sella turcica atypical teratoid/rhabdoid tumor complicated with lung metastasis
      in an adult female.
AB  - Here we present the case of a 60-year-old woman with a rare sellar region
      atypical teratoid/rhabdoid tumor (AT/RT), complicated by lung metastasis and
      treated with neurosurgery, radiotherapy, and chemotherapy. The patient had
      recurrent headache associated with left cavernous sinus syndrome after a previous
      endonasal transsphenoidal resection for a presumptive pituitary macroadenoma.
      Pituitary magnetic resonance imaging showed a tumor regrowth in the original
      location with a haemorrhagic component involving the left cavernous sinus. A near
      complete transsphenoidal resection of the sellar mass was performed followed by 3
      months of stereotactic radiotherapy. Because of a worsening of the general
      clinical conditions, respiratory failure, and asthenia, the patient underwent a
      contrast enhanced computer tomography of the whole body which showed the presence
      of lung metastasis. The histopathological diagnosis on samples from pituitary and
      lung tissues was AT/RT. The patient survived 30 months after diagnosis regardless
      chemotherapy. In the adult, the AT/RT should be considered as a possible rare,
      aggressive, and malignant neoplasm localized in the sella turcica. 

PMID- 24324355
TI  - Erratum for "metastatic castration-resistant prostate cancer: critical review of
      enzalutamide".

PMID- 24324354
TI  - Tobramycin Inhalation Powder (TIP): An Efficient Treatment Strategy for the
      Management of Chronic Pseudomonas Aeruginosa Infection in Cystic Fibrosis.
AB  - Repeated bouts of acute and chronic lung infections are responsible for
      progressive pulmonary function decline in individuals with cystic fibrosis (CF),
      ultimately leading to respiratory failure and death. Pseudomonas aeruginosa is
      the archetypical CF pathogen, causes chronic infection in 70% of individuals, and
      is associated with an accelerated clinical decline. The management of P.
      aeruginosa in CF has been revolutionized with the development and widespread use
      of inhaled antibiotics. Aerosol delivery of antimicrobial compounds in CF enables
      extremely high concentrations of antibiotics to be reached directly at the site
      of infection potentially overcoming adaptive resistance and avoiding the
      potential for cumulative systemic toxicities. Tobramycin inhalation powder (TIP)
      represents the first dry powder inhaled (DPI) antibiotic available for use in CF.
      DPIs are notable for a markedly reduced time for administration, ease of
      portability, and increased compliance. TIP has been developed as a therapeutic
      alternative to tobramycin inhalation solution (TIS), the standard of care for the
      past 20 years within CF. Relative to TIS 300 mg nebulized twice daily in on-and
      off cycles of 28 days duration, TIP 112 mg twice daily via the T-326 inhaler
      administered on the same schedule is associated with marked time savings,
      increased patient satisfaction, and comparable clinical end points. TIP
      represents an innovative treatment strategy for those individuals with CF and
      holds the promise of increased patient compliance and thus the potential for
      improved clinical outcomes. 

PMID- 24324356
TI  - Benign pairs: a significant entity in aspiration cytology smears from breast
      lesions.
AB  - INTRODUCTION: Fine needle aspiration cytology (FNAC) is a reliable diagnostic
      tool used to diagnose breast lesions preoperatively. However, FNAC is also
      associated with diagnostic pitfalls. Further studies are needed to improve its
      diagnostic efficacy. We noticed ovoid, bare nuclei arranged in closely touching
      diads (benign pairs) in a significant number of cytology smears. This prompted us
      to assess their diagnostic utility. MATERIALS AND METHODS: This was a prospective
      study conducted in Sarojini NaiduMedical College, Agra, India. Quantitative
      estimation of benign pairs per 1000 ductal cells in at least 20 high power field
      was attempted in cytology smears of 128 cases. RESULTS: The average number of
      pairs in benign and malignant lesions was calculated as 7.07 + 5.96 and 0.28 +
      0.78, respectively. Statistical analysis showed a significant difference between
      the number of pairs in benign and malignant cases (P < 0.0005). CONCLUSIONS:
      Quantitative estimation of benign pairs is helpful in distinguishing benign from
      malignant cases.

PMID- 24324357
TI  - Insights into the hallmarks of human nucleus pulposus cells with particular
      reference to cell viability, phagocytic potential and long process formation.
AB  - OBJECTIVE: As a main cellular component within the disc, nucleus pulposus (NP)
      cells play important roles in disc physiology. However, little is known on the
      biologic hallmarks of human NP cells. Therefore, the present study aimed to
      address the features of human NP cells. METHODS: Human NP samples were collected
      from normal cadavers, patients with scoliosis and disc degeneration as normal,
      disease control and degenerative NP, respectively. The NP samples were studied
      using transmission electron microscopy and TUNEL assay. Pre-digested NP samples
      were studied using flow cytometry with PI/Annexin V staining. RESULTS: Both
      control and degenerative human NP consisted of mainly viable cells with a variety
      of morphology. Both necrosis and apoptosis were noted in human NP as forms of
      cell death with increased apoptosis in degenerative NP, which was further
      confirmed by the TUNEL assay. Phagocytic NP cells had the hallmarks of both
      stationary macrophages with lysosomes and NP cells with the endoplasmic
      reticulum. Annulus fibrosus cells have similar morphologic characteristics with
      NP cells in terms of cell nest, phagocytosis and intracellular organs. Moreover,
      NP cells with long processes existed in degenerative and scoliotic NP rather than
      normal NP. When cultured in glucose-free medium, NP cells developed long and thin
      processes. CONCLUSION: Human degenerative NP consists of primarily viable cells.
      We present direct and in vivo evidence that both human annulus fibrosus and NP
      cells have phagocytic potential. Moreover, NP cells with long processes exist in
      both scoliotic and degenerative NP with lack of glucose as one of the possible
      underlying mechanisms.

PMID- 24324358
TI  - Evaluation of antiviral activities of four local Malaysian Phyllanthus species
      against herpes simplex viruses and possible antiviral target.
AB  - Nucleoside analogues such as acyclovir are effective antiviral drugs against
      herpes simplex virus infections since its introduction. However, with the
      emergence of acyclovir-resistant HSV strains particularly in immunocompromised
      patients, there is a need to develop an alternative antiherpetic drug and plants
      could be the potential lead. In this study, the antiviral activity of the aqueous
      extract of four Phyllanthus species were evaluated against herpes simplex virus
      type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein
      expressions of untreated and treated infected Vero cells were studied by 2D-gel
      electrophoresis and Western blot. This is the first study that reported the
      antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the
      strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of
      addition studies suggested that the extract may act against the early infection
      stage and the replication stage. Protein expression studies indicated that
      cellular proteins that are involved in maintaining cytoskeletal structure could
      be potential target for development of antiviral drugs. Preliminary findings
      indicated that P. urinaria demonstrated potent inhibitory activity against HSV.
      Hence, further studies such as in vivo evaluation are required for the
      development of effective antiherpetic drug. 

PMID- 24324359
TI  - Spontaneous weight change during chronic hepatitis C treatment: association with
      virologic response rates.
AB  - OBJECTIVE: We examined weight changes during chronic hepatitis C (CHC) therapy
      and association with virologic response. METHODS: Weight changes were compared
      between subjects achieving rapid, early, and sustained virologic response rates
      (RVR, EVR, and SVR). RVR, EVR and SVR were compared among patients with or
      without weight loss of >= 0.5 body mass index (BMI) units (kg/m2) at 4, 12, 48
      weeks. RESULTS: CHC therapy was initiated in 184 cases. Median pretreatment BMI
      was 27.7 (18.4-51.3) with 38% overweight and 31% obese (BMI >=25 and >= 30,
      respectively). Among patients with liver biopsies (n = 90), steatosis was present
      in 31.6%; fibrosis grade of 1-2/6 in 46%, 3-4 in 37.3% and 5-6 in 14.7%. Mean
      weight loss at 4, 12, 24 and 48 weeks of therapy were 1.2, 2.6, 3.8 and 3.3 kg,
      respectively. After 4 and 12 weeks of treatment, 38% and 54.3% had a BMI
      decrement of >= 0.5 kg/m2. For genotype 1, weight loss at 4 weeks was associated
      with significantly higher EVR (90.0% vs. 70%, p = 0.01) and a tendency towards
      better RVR and SVR (42.9% vs. 26.0% and 55.2% vs. 34.8%, respectively, p = 0.08).
      In multivariate analysis, weight loss at 4 weeks was independently associated
      with EVR (OR 6.3, p = 0.02) but was not significantly associated with RVR or SVR.
      CONCLUSIONS: Spontaneous weight loss at 4 and 12 weeks of CHC therapy was
      associated with improved EVR. Weight loss at 4 weeks was an independent predictor
      of EVR but not SVR.

PMID- 24324360
TI  - Extracellular matrix of mechanically stretched cardiac fibroblasts improves
      viability and metabolic activity of ventricular cells.
AB  - BACKGROUND: In heart, the extracellular matrix (ECM), produced by cardiac
      fibroblasts, is a potent regulator of heart's function and growth, and provides a
      supportive scaffold for heart cells in vitro and in vivo. Cardiac fibroblasts are
      subjected to mechanical loading all the time in vivo. Therefore, the influences
      of mechanical loading on formation and bioactivity of cardiac fibroblasts ECM
      should be investigated. METHODS: Rat cardiac fibroblasts were cultured on
      silicone elastic membranes and stimulated with mechanical cyclic stretch. After
      removing the cells, the ECMs coated on the membranes were prepared, some ECMs
      were treated with heparinase II (GAG-lyase), then the collagen, glycosaminoglycan
      (GAG) and ECM proteins were assayed. Isolated neonatal rat ventricular cells were
      seeded on ECM-coated membranes, the viability and lactate dehydrogenase (LDH)
      activity of the cells after 1-7 days of culture was assayed. In addition, the
      ATPase activity and related protein level, glucose consumption ratio and lactic
      acid production ratio of the ventricular cells were analyzed by
      spectrophotometric methods and Western blot. RESULTS: The cyclic stretch
      increased collagen and GAG levels of the ECMs, and elevated protein levels of
      collagen I and fibronectin. Compared with the ECMs produced by unstretched
      cardiac fibroblasts, the ECMs of mechanically stretched fibroblasts improved
      viability and LDH activity, elevated the Na+/K+-ATPase activity,
      sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity and SERCA 2a protein
      level, glucose consumption ratio and lactic acid production ratio of ventricular
      cells seeded on them. The treatment with heparinase II reduced GAG levels of
      these ECMs, and lowered these metabolism-related indices of ventricular cells
      cultured on the ECMs. CONCLUSIONS: Mechanical stretch promotes ECM formation of
      cardiac fibroblasts in vitro, the ECM of mechanically stretched cardiac
      fibroblasts improves metabolic activity of ventricular cells cultured in vitro,
      and the GAG of the ECMs is involved in regulating metabolic activity of
      ventricular cells.

PMID- 24324361
TI  - Distinct effects of RGD-glycoproteins on Integrin-mediated adhesion and
      osteogenic differentiation of human mesenchymal stem cells.
AB  - The detailed interactions of mesenchymal stem cells (MSCs) with their
      extracellular matrix (ECM) and the resulting effects on MSC differentiation are
      still largely unknown. Integrins are the main mediators of cell-ECM interaction.
      In this study, we investigated the adhesion of human MSCs to fibronectin,
      vitronectin and osteopontin, three ECM glycoproteins which contain an integrin
      binding sequence, the RGD motif. We then assayed MSCs for their osteogenic
      commitment in the presence of the different ECM proteins. As early as 2 hours
      after seeding, human MSCs displayed increased adhesion when plated on
      fibronectin, whereas no significant difference was observed when adhering either
      to vitronectin or osteopontin. Over a 10-day observation period, cell
      proliferation was increased when cells were cultured on fibronectin and
      osteopontin, albeit after 5 days in culture. The adhesive role of fibronectin was
      further confirmed by measurements of cell area, which was significantly increased
      on this type of substrate. However, integrin-mediated clusters, namely focal
      adhesions, were larger and more mature in MSCs adhering to vitronectin and
      osteopontin. Adhesion to fibronectin induced elevated expression of alpha5
      integrin, which was further upregulated under osteogenic conditions also for
      vitronectin and osteopontin. In contrast, during osteogenic differentiation the
      expression level of beta3-integrin was decreased in MSCs adhering to the
      different ECM proteins. When MSCs were cultured under osteogenic conditions,
      their commitment to the osteoblast lineage and their ability to form a
      mineralized matrix in vitro was increased in presence of fibronectin and
      osteopontin. Taken together these results indicate a distinct role of ECM
      proteins in regulating cell adhesion, lineage commitment and phenotype of MSCs,
      which is due to the modulation of the expression of specific integrin subunits
      during growth or osteogenic differentiation.

PMID- 24324362
TI  - Identification of hypermethylation in hepatocyte cell adhesion molecule gene
      promoter region in bladder carcinoma.
AB  - BACKGROUND: Epigenetic regulation such as aberrant hypermethylation of CpG
      islands in promoter plays a key role in tumorigenesis. 5-Aza-2'-deoxycytidine (5
      aza-CdR) which is a potent inhibitor of DNA methylation can reverse the abnormal
      hypermethylation of the silenced tumor suppressor genes (TSGs). It has been
      reported that hepatocyte cell adhesion molecule (hepaCAM) acts as a tumor
      suppressor gene and expression of its mRNA and protein were down-regulated in
      bladder cancer. Over-expression of hepaCAM can inhibit cancer growth and arrest
      renal cancer cells at G0/G1 phase. In this study, we investigated the methylation
      status of hepaCAM gene, as well as the influence of 5-aza-CdR on expression of
      hepaCAM gene in bladder cancer cells. METHODS: CpG islands in hepaCAM promoter
      and methprimers were predicted and designed using bioinformatics program.
      Methylation status of hepaCAM promoter was evaluated in bladder cancer tissues
      and two cell lines (T24 and BIU-87) by Methylation-specific PCR; Western blot and
      Immunofluorescence were used to detect expression of hepaCAM protein after 5-aza
      CdR treatment; Flow cytometry assay was performed to determine effectiveness of 5
      aza-CdR on cell cycle profile. RESULTS: CpG island in promoter of hepaCAM gene
      was hyper-methylated both in bladder carcinoma tissues and cell lines (T24 and
      BIU-87). Otherwise, aberrant methylation of its promoter was associated with its
      decreased expression. Hypermethylation of hepaCAM gene was reversed and
      expression of its mRNA and protein were re-activated in two cell lines by DNA
      methyltransferases inhibitor 5-aza-CdR. Flow cytometry assay demonstrated that 5
      aza-CdR can inhibit growth of cancer cells by arresting cancer cells at G0/G1
      phase. CONCLUSION: Abnormal hypermethylation in CpG island of hepaCAM promoter is
      involved in absence of hepaCAM gene expression when bladder cancer occurs. Re
      activation of hepaCAM gene by 5-aza-CdR can inhibit growth of cancer cells and
      arrest cells at G0/G1 phase.

PMID- 24324363
TI  - FGFR4 and TGF-beta1 expression in hepatocellular carcinoma: correlation with
      clinicopathological features and prognosis.
AB  - OBJECTIVE: To investigate the expression and correlation of transforming growth
      factor-beta1 (TGF-beta1) and fibroblast growth factor receptor 4 (FGFR4) in human
      hepatocellular carcinoma (HCC) and the relationship with clinicopathological
      features and prognosis. MATERIALS AND METHODS: The expression of TGF-beta1 and
      FGFR4 in 126 HCC samples was detected immunohistochemically. Combined with
      clinical postoperative follow-up data, the expression of TGF-beta1 and FGFR4 in
      HCC and the relationship with the prognosis of patients were analyzed by
      statistically. RESULTS: The positive expression rate of TGF-beta1 was 84.1%
      (106/126) in tumors, and that in peritumoral liver tissues was 64.3% (81/126);
      the positive expression rate of FGFR4 in tumors was 74.6% (94/126) and that in
      peritumoral liver tissues was 57.1% (72/126). The expression of TGF-beta1 and
      FGFR4 in the carcinoma tissues was significantly higher than that in peritumoral
      liver tissues (p < 0.05). Intratumoral TGF-beta1 and FGFR4 expression was
      associated with TNM stage (p < 0.05). TGF-beta1 and FGFR4 expression levels
      didn't significantly correlate with other clinicopathological parameters,
      including age, sex, tumor size, serum AFP level, tumor differentiation, lymph
      node metastasis, etc. (p > 0.05). TGF-beta1 expression was positively correlated
      with FGFR4 expression (r = 0.595, p < 0.05). Patients with positive FGFR4 or TGF
      beta1 expression had shorter overall survival compared with negative expression
      (p < 0.05). CONCLUSIONS: The expression of TGF-beta1 and FGFR4 could make synergy
      on the occurrence and progression of HCC, and may be used as prognosis indicators
      for HCC patients.

PMID- 24324364
TI  - Changes in left ventricular filling in patients with persistent atrial
      fibrillation.
AB  - BACKGROUND: Former studies showed possible interrelationship between altered
      ventricular filling patterns and atrial fibrillation (AF). HYPOTHESIS: Long term
      persistent AF has a negative impact on left ventricular filling in patients with
      preserved ejection fraction of left ventricle. METHODS: Our study was designed as
      a prospective case control study. We included 40 patients with persistent AF and
      preserved ejection fraction after successful electrical cardioversion and 43
      control patients. Persistent AF was defined as AF lasting more than 4 weeks.
      Cardiac ultrasound was performed in all patients 24 hours after the procedure.
      Appropriate mitral flow and tissue Doppler velocities as well as standard
      echocardiographic measurements were obtained. RESULTS: There were no significant
      differences between both groups' parameters regarding age, sex, commorbidities or
      drug therapy. Analysis of mitral flow velocities showed significant increase of E
      value in AF group (0.96+/-0.27 vs.0.70+/-0.14; p = 0.001). Tissue Doppler
      measurements didn't reveal any differences in early diastolic movement, however
      there was a statistically significant difference in E/Em values of both groups,
      respectively (12.0+/-4.0 vs. 9.0+/-2.1; p= 0.001). CONCLUSION: Our study shows
      that in patients with preserved systolic function and persistent AF shortly after
      cardioversion diastolic ventricular filling patterns are altered mainly due to
      increased left atrial pressure and not due to impaired diastolic relaxation of
      left ventricle. Further studies are needed in order to define the interplay
      between diminished atrial function and impaired ventricular filling.

PMID- 24324365
TI  - Impact of the training on the compliance and persistence of weekly bisphosphonate
      treatment in postmenopausal osteoporosis: a randomized controlled study.
AB  - Long-term patient adherence to osteoporosis treatment is poor despite proven
      efficacy. In this study, we aimed to assess the impact of active patient training
      on treatment compliance and persistence in patients with postmenopausal
      osteoporosis. In the present national, multicenter, randomized controlled study,
      postmenopausal osteoporosis patients (45-75 years) who were on weekly
      bisphosphonate treatment were randomized to active training (AT) and passive
      training (PT) groups and followed-up by 4 visits after the initial visit at 3
      months interval during 12 months of the treatment. Both groups received a
      bisphosphonate usage guide and osteoporosis training booklets. Additionally, AT
      group received four phone calls (at 2(nd), 5(th), 8(th), and 11(th) months) and
      participated to four interactive social/training meetings held in groups of 10
      patients (at 3(rd), 6(th), 9(th), and 12(th) months). The primary evaluation
      criteria were self-reported persistence and compliance to the treatment and the
      secondary evaluation criteria was quality life of the patients assessed by 41
      item Quality of Life European Foundation for Osteoporosis (QUALEFFO-41)
      questionnaire. Of 448 patients (mean age 62.4+/-7.7 years), 226 were randomized
      to AT group and 222 were randomized to PT group. Among the study visits, the most
      common reason for not receiving treatment regularly was forgetfulness (54.9% for
      visit 2, 44.3% for visit 3, 51.6% for visit 4, and 43.8% for visit 5), the
      majority of the patients always used their drugs regularly on recommended days
      and dosages (63.8% for visit 2, 60.9% for visit 3, 72.1% for visit 4, and 70.8%
      for visit 5), and most of the patients were highly satisfied with the treatment
      (63.4% for visit 2, 68.9% for visit 3, 72.4% for visit 4, and 65.2% for visit 5)
      and wanted to continue to the treatment (96.5% for visit 2, 96.5% for visit 3,
      96.9% for visit 4, and 94.4% for visit 5). QUALEFFO scores of the patients in
      visit 1 significantly improved in visit 5 (37.7+/-25.4 vs. 34.0+/-14.6, p<0.001);
      however, the difference was not significant between AT and PT groups both in
      visit 1 and visit 5. In conclusion, in addition to active training, passive
      training provided at the 1(st) visit did not improve the persistence and
      compliance of the patients for bisphosphonate treatment.

PMID- 24324366
TI  - Modulation of beta-catenin signaling by the inhibitors of MAP kinase, tyrosine
      kinase, and PI3-kinase pathways.
AB  - Aberrant activation of beta-catenin signaling plays an important role in human
      tumorigenesis. However, molecular mechanisms behind the beta-catenin signaling
      deregulation are mostly unknown because genetic alterations in this pathway only
      account for a small fraction of tumors. Here, we investigator if other major
      pathways can regulate beta-catenin signaling activity. By employing a panel of
      chemical activators and/or inhibitors of several cellular signaling pathways, we
      assess these modulators' effects on luciferase reporter driven by beta
      catenin/TCF4-responsive elements. We find that lithium-stimulated beta-catenin
      activity is synergistically enhanced by protein kinase C activator PMA. However,
      beta-catenin-regulated transcriptional (CRT) activity is significantly inhibited
      by casein kinase II inhibitor DRB, MEK inhibitor PD98059, G-proteins and their
      receptor uncoupling agent suramin, protein tyrosine kinase inhibitor genistein,
      and PI-3 kinase inhibitor wortmannin, suggesting that these cellular pathways may
      participate in regulating beta-catenin signaling. Interestingly, the
      Ca++/calmodulin kinase II inhibitor HDBA is shown to activate beta-catenin
      activity at low doses. Furthermore, Wnt3A-stimulated and constitutively activated
      CRT activities, as well as the intracellular accumulation of beta-catenin protein
      in human colon cancer cells, are effectively suppressed by PD98059, genistein,
      and wortmannin. We further demonstrate that EGF can activate TCF4/beta-catenin
      activity and induce the tyrosine phosphorylation of beta-catenin protein. Thus,
      our results should provide important insights into the molecular mechanisms
      underlying Wnt/beta-catenin activation. This knowledge should facilitate our
      efforts to develop efficacious and novel therapeutics by targeting these
      pathways.

PMID- 24324367
TI  - Recombinant human adiponectin as a potential protein for treating diabetic
      tendinopathy promotes tenocyte progenitor cells proliferation and tenogenic
      differentiation in vitro.
AB  - Adiponectin is an adipocyte-secreting hormone that increases cell sensitivity to
      insulin. It has been previously demonstrated that this hormone protects against
      Type II Diabetes and, is found to concurrently promote cell proliferation and
      differentiation. It is postulated that diabetic patients who suffer from
      tendinopathy may benefit from using adiponectin, which not only improves the
      metabolism of diabetic ridden tenocytes but also promotes progenitor cell
      proliferation and differentiation in tendons. These changes may result in tendon
      regeneration, which, in diabetic tendinopathy, is difficult to treat. Considering
      that such findings have yet to be demonstrated, a study was thus conducted using
      diabetic ridden human tenocyte progenitor cells (TPC) exposed to recombinant
      adiponectin in vitro. TPC were isolated from tendons of diabetic patients and
      exposed to 10 MUg/ml adiponectin. Cell proliferation rate was investigated at
      various time points whilst qPCR were used to determine the tenogenic
      differentiation potential. The results showed that adiponectin significantly
      reduced blood glucose in animal models. The proliferation rate of adiponectin
      treated TPCs was significantly higher at 6, 8 and 10 days as compared to
      untreated cells (p<0.05). The levels of tenogenic genes expression (collagen I,
      III, tenomodulin and scleraxis) were also significantly upregulated; whilst the
      osteogenic (Runx2), chondrogenic (Sox9) and adipogenic (PPARUgamma) gene
      expressions remained unaltered. The results of this study suggest that
      adiponectin is a potential promoter that not only improves diabetic conditions,
      but also increases tendon progenitor cell proliferation and differentiation.
      These features supports the notion that adiponectin may be potentially beneficial
      in treating diabetic tendinopathy.

PMID- 24324368
TI  - Glucose-6-phosphate dehydrogenase deficiency and diabetes mellitus with severe
      retinal complications in a Sardinian population, Italy.
AB  - BACKGROUND: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is one of the
      most common human genetic abnormalities, with a high prevalence in Sardinia,
      Italy. Evidence indicates that G6PD-deficient patients are protected against
      vascular disease. Little is known about the relationship between G6PD deficiency
      and diabetes mellitus. The purpose of this study was to compare G6PD deficiency
      prevalence in Sardinian diabetic men with severe retinal vascular complications
      and in age-matched non-diabetic controls and ascertain whether G6PD deficiency
      may offer protection against this vascular disorder. METHODS: Erythrocyte G6PD
      activity was determined using a quantitative assay in 390 diabetic men with
      proliferative diabetic retinopathy (PDR) and 390 male non-diabetic controls, both
      aged >=50 years. Conditional logistic regression models were used to investigate
      the association between G6PD deficiency and diabetes with severe retinal
      complications. RESULTS: G6PD deficiency was found in 21 (5.4 %) diabetic patients
      and 33 (8.5 %) controls (P=0.09). In a univariate conditional logistic regression
      model, G6PD deficiency showed a trend for protection against diabetes with PDR,
      but the odds ratio (OR) fell short of statistical significance (OR=0.6, 95%
      confidence interval=0.35-1.08, P=0.09). In multivariate conditional logistic
      regression models, including as covariates G6PD deficiency, plasma glucose, and
      systemic hypertension or systolic or diastolic blood pressure, G6PD deficiency
      showed no statistically significant protection against diabetes with PDR.
      CONCLUSIONS: The prevalence of G6PD deficiency in diabetic men with PDR was lower
      than in age-matched non-diabetic controls. G6PD deficiency showed a trend for
      protection against diabetes with PDR, but results were not statistically
      significant.

PMID- 24324369
TI  - Higher dosage of HIFU treatment may lead to higher and longer efficacy for
      moderate to severe perennial allergic rhinitis.
AB  - OBJECTIVES: This study was to compare the efficacies and side effects of high
      intensity focused ultrasound (HIFU) treatment for perennial allergic rhinitis
      (PAR) with regular and increased dosage. STUDY DESIGN: A prospectively assembled
      cohort was retrospectively analyzed through visual analogue scale (VAS). METHODS:
      Regular dosage of HIFU treatment was applied to 56 PAR patients in group A. An
      increased dosage as twice as the regular one was applied to 48 patients in group
      B. Nasal obstruction, sneezing, rhinorrhea and rhinocnesmus, which were
      recognized as the four main symptoms of allergic rhinitis (AR), were evaluated
      before treatment, 3 months after treatment, and 1 year after treatment. The
      satisfaction of patients was also evaluated at 1 year postoperatively. Biopsy of
      the inferior turbinate and morphometric analysis were applied to 11 patients in
      group A and 10 in group B before HIFU treatment and 3 months after treatment.
      RESULTS: Comparing the AR symptoms before treatment, There is no statistical
      difference observed between group A and B (p>0.05). The four main symptoms at 3
      months and 1 year after treatment were all significantly improved (p<0.01) in
      both group A and B. The VAS scores of AR symptoms in Group B were lower than
      those in Group A at the same stage after treatment, especially at 1 year after
      treatment (p<0.05). Comparing the results at 3 months and 1 year after treatment,
      a tendency of recurrence of these symptoms was observed statistically in group A
      (p<0.05), but not in group B (p>0.05). More cases of nasal dryness and perirhinal
      swelling were found in group B than those in group A (p<0.05), while all side
      effects were mild and temporary. Patients in group B were more satisfied than
      those in group A (p=0.0866 >0.05), though not statistically significant. More
      reduction of the eosinophils, other inflammatory cells, and the submucosal glands
      was observed after HIFU treatment in group B than that in group A (p<0.05).
      CONCLUSIONS: A proper increment of HIFU dosage may be recommended to meet the
      needs of more improvement of AR symptoms and less recurrence.

PMID- 24324370
TI  - Spatiotemporal variations of the 90Sr in the southern part of the Baltic Sea over
      the period of 2005-2010.
AB  - The Baltic Sea is one of the most contaminated seas by the radioactive isotope of
      strontium in the world; therefore the activity of 90Sr is regularly controlled.
      Due to that fact, seawater samples for 90Sr determination were collected at 16
      stations located in the southern Baltic Sea between 2005 and 2010. In this period
      average activity of 90Sr was 7.8 Bq m-3 and varied within the range from 3.0 Bq m
      3 to 11.9 Bq m-3. Because the higher activity of 90Sr was measured in the Baltic
      Sea than in the North Sea and rivers, inflows from the North Sea and the riverine
      runoff decreased 90Sr activity in the Baltic Sea. The average 90Sr activity in
      the bottom water along the offshore profile was 18% lower than that in the
      surface water and it was caused by an inflow of salt water from the North Sea. In
      the Vistula River mouth the average activity of 90Sr in the surface water was
      about 15% lower than the average activity in the bottom waters. Coastal areas,
      relatively shallow with good mixing condition in the water column, were
      characterized by low variability in 90Sr activity.

PMID- 24324372
TI  - The significance of IDH1 mutations in tumor-associated seizure in 60 Chinese
      patients with low-grade gliomas.
AB  - BACKGROUND: Seizure is a common clinical presentation in patients suffering from
      primary brain tumors, especially from low-grade gliomas (LGGs). However, the
      genetic factors of tumor-associated seizure, at present, are still very poorly
      understood. The aim of this study was to investigate the potential correlation
      between tumor-associated epilepsy and IDH1 mutations in a Chinese population with
      LGGs. MATERIALS AND METHODS: This study reviewed 60 patients with histologically
      confirmed low-grade gliomas, and the status of IDH1 was detected after the
      operation at our institution. Univariate and multivariate logistic regression
      analysis were used to explore the potential risk factors for tumor-related
      seizures. Results. IDH1 mutation was detected in 46 (76.7%) patients, among which
      14 patients had no epilepsies and 32 patients had epilepsies (P = 0.023, chi
      square test). Multivariate logistic regression analysis demonstrated that the
      mutation of IDH1 seems to be the strongest predictor for preoperative seizure
      (OR, 6.130; 95% CI, 1.523-24.669; P = 0.011). CONCLUSIONS: IDH1 mutation was
      frequently detected in LGGs, and it may result in tumor-related seizures.

PMID- 24324371
TI  - Perioperative variables contributing to the rupture of intracranial aneurysm: an
      update.
AB  - BACKGROUND: Perioperative aneurysm rupture (PAR) is one of the most dreaded
      complications of intracranial aneurysms, and approximately 80% of nontraumatic
      SAHs are related to such PAR aneurysms. The literature is currently scant and
      even controversial regarding the issues of various contributory factors on
      different phases of perioperative period. Thus this paper highlights the current
      understanding of various risk factors, variables, and outcomes in relation to PAR
      and try to summarize the current knowledge. METHOD: We have performed a PubMed
      search (1 January 1991-31 December 2012) using search terms including "cerebral
      aneurysm," "intracranial aneurysm," and "intraoperative/perioperative rupture."
      RESULTS: Various risk factors are summarized in relation to different phases of
      perioperative period and their relationship with outcome is also highlighted.
      There exist many well-known preoperative variables which are responsible for the
      highest percentage of PAR. The role of other variables in the
      intraoperative/postoperative period is not well known; however, these factors may
      have important contributory roles in aneurysm rupture. Preoperative variables
      mainly include natural course (age, gender, and familial history) as well as the
      pathophysiological factors (size, type, location, comorbidities, and procedure).
      Previously ruptured aneurysm is associated with rupture in all the phases of
      perioperative period. On the other hand intraoperative/postoperative variables
      usually depend upon anesthesia and surgery related factors. Intraoperative
      rupture during predissection phase is associated with poor outcome while
      intraoperative rupture at any step during embolization procedure imposes poor
      outcome. CONCLUSION: We have tried to create such an initial categorization but
      know that we cannot scale according to its clinical importance. Thorough
      understanding of various risk factors and other variables associated with PAR
      will assist in better clinical management as well as patient care in this group
      and will give insight into the development and prevention of such a catastrophic
      complication in these patients.

PMID- 24324373
TI  - Proprioception in above-the-knee amputees with artificial limbs.
AB  - PURPOSE: To evaluate the lower limb proprioceptive sensation in patients with
      femoral amputation who received an artificial joint. MATERIALS AND METHODS: 22
      patients (18 men, 4 women), 24-65 years old (mean: 42), who had undergone above
      the-knee joint amputation and underwent evaluation of proprioception using joint
      reposition in a predetermined angle of 15 degrees  knee flexion. The measurements
      were applied using a conventional goniometer to both amputated and healthy knees.
      The last ones were used as internal control. All patients performed an active
      knee flexion from hyperextension to 15 degrees  in a closed kinetic chain in
      order to evaluate proprioceptive sensation of the knee joint using the joint
      position sense (JPS) method during specific controllable circumstances very close
      to normal gait. RESULTS: JPS at 15 degrees  flexion for the amputated knee was
      calculated to be equal to 13.91 (SD = +/-4.74), and for the healthy side it was
      equal to 14.15 (SD = +/-2.61). No statistically significant differences were
      detected between the amputated and the healthy limb (P > 0.05). CONCLUSIONS: The
      proprioceptive information of the stumps did not appear to be affected
      significantly after thigh amputation and application of artificial prosthesis
      when JPS at 15 degrees  was evaluated. It seems that these patients compensate
      the loss of the knee sensory receptors via alternative mechanisms.

PMID- 24324374
TI  - Evaluation and optimization of downstream process parameters for extraction of
      betulinic acid from the bark of Ziziphus jujubae L.
AB  - Present work investigated an apposite and efficient method for extraction of
      betulinic acid (BA) from the bark of Ziziphus jujubae. Various extraction methods
      like stirring extraction, soxhlet extraction, ultrasonic extraction, and
      microwave assisted extraction (MAE) were evaluated for increasing recovery
      percentage of BA. From the raffinate so obtained, BA was isolated. Thin layer
      chromatography (TLC) was used to analyze the extract and high performance liquid
      chromatography (HPLC) for quantification. The results revealed that the
      percentage extraction of BA from Z. jujubae by MAE was more proficient. As
      recovery percentage of BA by MAE technique turned out to be maximum, by using
      response surface methodology (RSM), three process parameters (pH, temperature,
      and time) were optimized by MAE and it was observed that the optimum parameters
      (pH 6.5, temp. 70.23 degrees C, and time 3.5 min) gave the maximum recovery of BA
      (0.44% w/w). To validate the RSM model, experiments were performed and the
      highest recovery of BA was found to be 0.4% w/w which is +/-0.04% to the
      predicted value. Henceforth the extraction efficiency and the substantial saving
      of time by MAE was more capable than the other extraction techniques. 

PMID- 24324375
TI  - In astrocytes the accumulation of the immunity-related GTPases Irga6 and Irgb6 at
      the vacuole of Toxoplasma gondii is dependent on the parasite virulence.
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite responsible for
      a common infection of the central nervous system. Interferon (IFN) gamma is the
      key cytokine of host defence against T. gondii. However, T. gondii strains differ
      in virulence and T. gondii factors determining virulence are still poorly
      understood. In astrocytes IFN gamma primarily induces immunity-related GTPases
      (IRGs), providing a cell-autonomous resistance system. Here, we demonstrate that
      astrocytes prestimulated with IFN gamma inhibit the proliferation of various
      avirulent, but not virulent, T. gondii strains. The two analyzed immunity-related
      GTPases Irga6 and Irgb6 accumulate at the PV only of avirulent T. gondii strains,
      whereas in virulent strains this accumulation is only detectable at very low
      levels. Both IRG proteins could temporarily be found at the same PV, but did only
      partially colocalize. Coinfection of avirulent and virulent parasites confirmed
      that the accumulation of the two analyzed IRGs was a characteristic of the
      individual PV and not determined by the presence of other strains of T. gondii in
      the same host cell. Thus, in astrocytes the accumulation of Irga6 and Irgb6
      significantly differs between avirulent and virulent T. gondii strains
      correlating with the toxoplasmacidal properties suggesting a role for this
      process in parasite virulence. 

PMID- 24324376
TI  - Relevance of biofilms in the pathogenesis of Shiga-toxin-producing Escherichia
      coli infection.
AB  - The present study was designed to determine the relationships among biofilm
      formation, cellular stress and release of Shiga toxin (Stx) by three different
      clinical Shiga toxin-producing Escherichia coli (STEC) strains. The biofilm
      formation was determined using crystal violet stain in tryptic soy broth or
      thioglycollate medium with the addition of sugars (glucose or mannose) or
      hydrogen peroxide. The reactive oxygen species (ROSs) were detected by the
      reduction of nitro blue tetrazolium and reactive nitrogen intermediates (RNI)
      determined by the Griess assay. In addition, the activities of two antioxidant
      enzymes, superoxide dismutase (SOD) and catalase (CAT), were studied. For the
      cytotoxicity studies, Vero cells were cultured with Stx released of STEC
      biofilms. The addition of sugars in both culture mediums resulted in an increase
      in biofilm biomass, with a decrease in ROS and RNI production, low levels of SOD
      and CAT activity, and minimal cytotoxic effects. However, under stressful
      conditions, an important increase in the antioxidant enzyme activity and high
      level of Stx production were observed. The disturbance in the prooxidant
      antioxidant balance and its effect on the production and release of Stx evaluated
      under different conditions of biofilm formation may contribute to a better
      understanding of the relevance of biofilms in the pathogenesis of STEC infection.

PMID- 24324377
TI  - The effect of postoperative corticosteroid administration on free vascularized
      fibular grafting for treating osteonecrosis of the femoral head.
AB  - Free vascularized fibular grafting (FVFG) has been reported to be an effective
      method of treating osteonecrosis of the femoral head (ONFH). This study evaluated
      whether postoperative maintenance doses of corticosteroids had an adverse effect
      on FVFG outcomes in patients with corticosteroid-induced ONFH. We retrospectively
      reviewed the records of 39 patients (67 hips) who had received maintenance doses
      of corticosteroids following FVFG. This group was matched to a group of patients
      who had not received corticosteroids treatment after operation. The mean follow
      up duration was 5.4 years for the postoperative corticosteroid administration
      group (PCA group) and 5.0 years for the control group. At the latest follow-up,
      the average increase in Harris hip score was 11.1 +/- 8.7 points for all hips in
      the PCA group and 12.6 +/- 7.4 points for all hips in the control group (P >
      0.05). In the PCA group, through radiographic evaluation, 49 hips were improved,
      10 hips appeared unchanged, and 8 hips appeared worse. In the control group, 47
      hips were improved, 13 hips appeared unchanged, and 7 hips appeared worse. The
      results suggested that postoperative maintenance doses of corticosteroids do not
      have an adverse effect on FVFG outcomes in patients with corticosteroid-induced
      ONFH. 

PMID- 24324378
TI  - A review on the fabrication of polymer-based thermoelectric materials and
      fabrication methods.
AB  - Thermoelectricity, by converting heat energy directly into useable electricity,
      offers a promising technology to convert heat from solar energy and to recover
      waste heat from industrial sectors and automobile exhausts. In recent years, most
      of the efforts have been done on improving the thermoelectric efficiency using
      different approaches, that is, nanostructuring, doping, molecular rattling, and
      nanocomposite formation. The applications of thermoelectric polymers at low
      temperatures, especially conducting polymers, have shown various advantages such
      as easy and low cost of fabrication, light weight, and flexibility. In this
      review, we will focus on exploring new types of polymers and the effects of
      different structures, concentrations, and molecular weight on thermoelectric
      properties. Various strategies to improve the performance of thermoelectric
      materials will be discussed. In addition, a discussion on the fabrication of
      thermoelectric devices, especially suited to polymers, will also be given.
      Finally, we provide the challenge and the future of thermoelectric polymers,
      especially thermoelectric hybrid model. 

PMID- 24324379
TI  - Using the virtual reality-cognitive rehabilitation approach to improve contextual
      processing in children with autism.
AB  - BACKGROUND: This pilot study investigated the efficacy of a novel virtual reality
      cognitive rehabilitation (VR-CR) intervention to improve contextual processing of
      objects in children with autism. Previous research supports that children with
      autism show deficits in contextual processing, as well as deficits in its
      elementary components: abstraction and cognitive flexibility. METHODS: Four
      children with autism participated in a multiple-baseline, single-subject study.
      The children were taught how to see objects in context by reinforcing attention
      to pivotal contextual information. RESULTS: All children demonstrated
      statistically significant improvements in contextual processing and cognitive
      flexibility. Mixed results were found on the control test and changes in context
      related behaviours. CONCLUSIONS: Larger-scale studies are warranted to determine
      the effectiveness and usability in comprehensive educational programs.

PMID- 24324380
TI  - Characterisation of structure-borne sound source using reception plate method.
AB  - A laboratory-based experiment procedure of reception plate method for structure
      borne sound source characterisation is reported in this paper. The method uses
      the assumption that the input power from the source installed on the plate is
      equal to the power dissipated by the plate. In this experiment, rectangular
      plates having high and low mobility relative to that of the source were used as
      the reception plates and a small electric fan motor was acting as the structure
      borne source. The data representing the source characteristics, namely, the free
      velocity and the source mobility, were obtained and compared with those from
      direct measurement. Assumptions and constraints employing this method are
      discussed. 

PMID- 24324382
TI  - Petrophysical properties (density and magnetization) of rocks from the Suhbaatar
      Ulaanbaatar-Dalandzadgad geophysical profile in Mongolia and their implications.
AB  - Petrophysical properties of 585 rock samples from the Suhbaatar-Ulaanbaatar
      Dalandzadgad geophysical profile in Mongolia are presented. Based on the rock
      classifications and tectonic units, petrophysical parameters (bulk density,
      magnetic susceptibility, intensity of natural remanent magnetization, and
      Koenigsberger ratio) of these rocks are summarized. Results indicate that (1)
      significant density contrast of different rocks would result in variable gravity
      anomalies along the profile; (2) magnetic susceptibility and natural remanent
      magnetization of all rocks are variable, covering 5-6 orders of magnitude, which
      would make a variable induced magnetization and further links to complex magnetic
      anomalies in ground surface; (3) the distribution of rocks with different
      lithologies controls the pattern of lithospheric magnetic anomaly along the
      profile. The petrophysical database thus provides not only one of the keys to
      understand the geological history and structure of the profile, but also
      essential information for analysis and interpretation of the geophysical (e.g.,
      magnetic and gravity) survey data. 

PMID- 24324383
TI  - On the performance of linear decreasing inertia weight particle swarm
      optimization for global optimization.
AB  - Linear decreasing inertia weight (LDIW) strategy was introduced to improve on the
      performance of the original particle swarm optimization (PSO). However, linear
      decreasing inertia weight PSO (LDIW-PSO) algorithm is known to have the
      shortcoming of premature convergence in solving complex (multipeak) optimization
      problems due to lack of enough momentum for particles to do exploitation as the
      algorithm approaches its terminal point. Researchers have tried to address this
      shortcoming by modifying LDIW-PSO or proposing new PSO variants. Some of these
      variants have been claimed to outperform LDIW-PSO. The major goal of this paper
      is to experimentally establish the fact that LDIW-PSO is very much efficient if
      its parameters are properly set. First, an experiment was conducted to acquire a
      percentage value of the search space limits to compute the particle velocity
      limits in LDIW-PSO based on commonly used benchmark global optimization problems.
      Second, using the experimentally obtained values, five well-known benchmark
      optimization problems were used to show the outstanding performance of LDIW-PSO
      over some of its competitors which have in the past claimed superiority over it.
      Two other recent PSO variants with different inertia weight strategies were also
      compared with LDIW-PSO with the latter outperforming both in the simulation
      experiments conducted. 

PMID- 24324381
TI  - Influence of physical activity and nutrition on obesity-related immune function.
AB  - Research examining immune function during obesity suggests that excessive
      adiposity is linked to impaired immune responses leading to pathology. The
      deleterious effects of obesity on immunity have been associated with the systemic
      proinflammatory profile generated by the secretory molecules derived from adipose
      cells. These include inflammatory peptides, such as TNF- alpha , CRP, and IL-6.
      Consequently, obesity is now characterized as a state of chronic low-grade
      systemic inflammation, a condition considerably linked to the development of
      comorbidity. Given the critical role of adipose tissue in the inflammatory
      process, especially in obese individuals, it becomes an important clinical
      objective to identify lifestyle factors that may affect the obesity-immune system
      relationship. For instance, stress, physical activity, and nutrition have each
      shown to be a significant lifestyle factor influencing the inflammatory profile
      associated with the state of obesity. Therefore, the purpose of this review is to
      comprehensively evaluate the impact of lifestyle factors, in particular
      psychological stress, physical activity, and nutrition, on obesity-related immune
      function with specific focus on inflammation. 

PMID- 24324384
TI  - Iron oxide impregnated Morus alba L. fruit peel for biosorption of Co(II):
      biosorption properties and mechanism.
AB  - Biosorption is an ecofriendly wastewater treatment technique with high efficiency
      and low operating cost involving simple process for the removal of heavy metal
      ions from aqueous solution. In the present investigation, Morus alba L. fruit
      peel powder (MAFP) and iron oxide impregnated Morus alba L. fruit peel powder (IO
      MAFP) were prepared and used for treating Co(II) contaminated aqueous solutions.
      Further the materials were characterized by using FTIR and SEM-EDX analysis. From
      FT-IR analysis it was found that hydroxyl, methoxy, and carbonyl groups are
      responsible for Co(II) biosorption. The kinetic data obtained for both
      biosorbents was well fitted with pseudo-second-order kinetic model. The
      equilibrium data was in tune with the Langmuir and Freundlich isotherm models.
      The thermodynamic studies were also carried and it was observed that sorption
      process was endothermic at 298-328 K. These studies demonstrated that both
      biosorbents were promising, efficient, economic, and biodegradable sorbents. 

PMID- 24324385
TI  - Overexpression of luxS cannot increase autoinducer-2 production, only affect the
      growth and biofilm formation in Streptococcus suis.
AB  - LuxS/AI-2 quorum sensing (QS) system involves the production of cell signaling
      molecules via luxS-based autoinducer-2 (AI-2). LuxS has been reported to plays
      critical roles in regulating various behaviors of bacteria. AI-2 is a byproduct
      of the catabolism of S-adenosylhomocysteine (SAH) performed by the LuxS and Pfs
      enzymes. In our previous study, the function of LuxS in AI-2 production was
      verified in Streptococcus suis (SS). Decreased levels of SS biofilm formation and
      host-cell adherence as well as an inability to produce AI-2 were observed in
      bacteria having a luxS mutant gene. In this study, the level of AI-2 activity
      exhibits a growth-phase dependence with a maximum in late exponential culture in
      SS. An SS strain that overexpressed luxS was constructed to comprehensively
      understand the function of AI-2. Overexpressed luxS was not able to increase the
      level of pfs expression and produce additional AI-2, and the bacteria were slower
      growing and produced only slightly more biofilm than the wild type. Thus, AI-2
      production is not correlated with luxS transcription. luxS expression is
      constitutive, but the transcription of pfs is perhaps correlated with AI-2
      production in SS. 

PMID- 24324386
TI  - An iterative algorithm for the reflexive solution of the general coupled matrix
      equations.
AB  - The general coupled matrix equations (including the generalized coupled Sylvester
      matrix equations as special cases) have numerous applications in control and
      system theory. In this paper, an iterative algorithm is constructed to solve the
      general coupled matrix equations over reflexive matrix solution. When the general
      coupled matrix equations are consistent over reflexive matrices, the reflexive
      solution can be determined automatically by the iterative algorithm within finite
      iterative steps in the absence of round-off errors. The least Frobenius norm
      reflexive solution of the general coupled matrix equations can be derived when an
      appropriate initial matrix is chosen. Furthermore, the unique optimal
      approximation reflexive solution to a given matrix group in Frobenius norm can be
      derived by finding the least-norm reflexive solution of the corresponding general
      coupled matrix equations. A numerical example is given to illustrate the
      effectiveness of the proposed iterative algorithm. 

PMID- 24324387
TI  - Phosphorescent molecularly doped light-emitting diodes with blended polymer host
      and wide emission spectra.
AB  - Stable green light emission and high efficiency organic devices with three
      polymer layers were fabricated using bis[2-(4'-tert-butylphenyl)-1-phenyl-1H
      benzoimidazole-N,C2'] iridium(III) (acetylacetonate) doped in blended host
      materials. The 1 wt% doping concentration showed maximum luminance of 7841 cd/cm2
      at 25.6 V and maximum current efficiency of 9.95 cd/A at 17.2 V. The
      electroluminescence spectra of devices indicated two main peaks at 522 nm and 554
      nm coming from phosphor dye and a full width at half maximum (FWHM) of 116 nm.
      The characteristics of using blended host, doping iridium complex, emission
      spectrum, and power efficiency of organic devices were investigated.

PMID- 24324388
TI  - Gene structures, classification, and expression models of the DREB transcription
      factor subfamily in Populus trichocarpa.
AB  - We identified 75 dehydration-responsive element-binding (DREB) protein genes in
      Populus trichocarpa. We analyzed gene structures, phylogenies, domain
      duplications, genome localizations, and expression profiles. The phylogenic
      construction suggests that the PtrDREB gene subfamily can be classified broadly
      into six subtypes (DREB A-1 to A-6) in Populus. The chromosomal localizations of
      the PtrDREB genes indicated 18 segmental duplication events involving 36 genes
      and six redundant PtrDREB genes were involved in tandem duplication events. There
      were fewer introns in the PtrDREB subfamily. The motif composition of PtrDREB was
      highly conserved in the same subtype. We investigated expression profiles of this
      gene subfamily from different tissues and/or developmental stages. Sixteen genes
      present in the digital expression analysis had high levels of transcript
      accumulation. The microarray results suggest that 18 genes were upregulated. We
      further examined the stress responsiveness of 15 genes by qRT-PCR. A digital
      northern analysis showed that the PtrDREB17, 18, and 32 genes were highly induced
      in leaves under cold stress, and the same expression trends were shown by qRT
      PCR. Taken together, these observations may lay the foundation for future
      functional analyses to unravel the biological roles of Populus' DREB genes. 

PMID- 24324389
TI  - Statistical optimization of process parameters for lipase-catalyzed synthesis of
      triethanolamine-based esterquats using response surface methodology in 2-liter
      bioreactor.
AB  - Lipase-catalyzed production of triethanolamine-based esterquat by esterification
      of oleic acid (OA) with triethanolamine (TEA) in n-hexane was performed in 2 L
      stirred-tank reactor. A set of experiments was designed by central composite
      design to process modeling and statistically evaluate the findings. Five
      independent process variables, including enzyme amount, reaction time, reaction
      temperature, substrates molar ratio of OA to TEA, and agitation speed, were
      studied under the given conditions designed by Design Expert software.
      Experimental data were examined for normality test before data processing stage
      and skewness and kurtosis indices were determined. The mathematical model
      developed was found to be adequate and statistically accurate to predict the
      optimum conversion of product. Response surface methodology with central
      composite design gave the best performance in this study, and the methodology as
      a whole has been proven to be adequate for the design and optimization of the
      enzymatic process.

PMID- 24324390
TI  - Hexahedral localization (HL): a three-dimensional hexahedron localization based
      on mobile beacons.
AB  - In wireless sensor networks, localization is one of the fundamental technologies
      and is essential to its applications. In this paper, we propose a three
      dimensional range-free localization scheme named hexahedral localization. In the
      scheme, the space is divided into a lot of hexahedrons. Then, all the unknown
      nodes are located by utilizing the perpendicular properties of the trajectory.
      The contribution of our scheme can be summarized into two points. First, it fills
      the gap of shortage of three-dimensional localization based on mobile beacons.
      Second, it brings in the outstanding localization accuracy. The simulation result
      reveals that this localization scheme has the relative high accuracy. At the end
      of the paper, the performance and error of our scheme are analyzed in aim of
      improving in the future work. 

PMID- 24324392
TI  - BIM: enabling sustainability and asset management through knowledge management.
AB  - Building Information Modeling (BIM) is the use of virtual building information
      models to develop building design solutions and design documentation and to
      analyse construction processes. Recent advances in IT have enabled advanced
      knowledge management, which in turn facilitates sustainability and improves asset
      management in the civil construction industry. There are several important
      qualifiers and some disadvantages of the current suite of technologies. This
      paper outlines the benefits, enablers, and barriers associated with BIM and makes
      suggestions about how these issues may be addressed. The paper highlights the
      advantages of BIM, particularly the increased utility and speed, enhanced fault
      finding in all construction phases, and enhanced collaborations and visualisation
      of data. The paper additionally identifies a range of issues concerning the
      implementation of BIM as follows: IP, liability, risks, and contracts and the
      authenticity of users. Implementing BIM requires investment in new technology,
      skills training, and development of new ways of collaboration and Trade Practices
      concerns. However, when these challenges are overcome, BIM as a new information
      technology promises a new level of collaborative engineering knowledge
      management, designed to facilitate sustainability and asset management issues in
      design, construction, asset management practices, and eventually decommissioning
      for the civil engineering industry. 

PMID- 24324391
TI  - The mitigating effect of Citrullus colocynthis (L.) fruit extract against
      genotoxicity induced by cyclophosphamide in mice bone marrow cells.
AB  - Possible genoprotective effect of Citrullus colocynthis (L.) (CCT) fruits extract
      against cyclophosphamide- (CP-)induced DNA damage in mice bone marrow cells was
      evaluated using micronucleus assay, as an index of induced chromosomal damage.
      Mice were preadministered with different doses of CCT via intraperitoneal
      injection for 7 consecutive days followed by injection with CP (70 mg/kg b.w.) 1
      hr after the last injection of CCT. After 24 hr, mice were scarified to evaluate
      the frequency of micronucleated polychromatic erythrocytes (MnPCEs). In addition,
      the number of polychromatic erythrocytes (PCEs) among 1000 normochromatic
      erythrocytes (NCEs) per animal was recorded to evaluate bone marrow. Pretreatment
      with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow
      cells (P < 0.0001). At 200 mg/kg, CCT had a maximum chemoprotective effect and
      reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic
      activity. CCT also led to marked proliferation and hypercellularity of immature
      myeloid elements after mice were treated with CP and mitigated the bone marrow
      suppression. Our study revealed that CCT has an antigenotoxic effect against CP
      induced oxidative DNA damage in mice. Therefore, it could be used concomitantly
      as a supplement to protect people undergoing chemotherapy.

PMID- 24324393
TI  - Modulation of gastrointestinal vagal neurocircuits by hyperglycemia.
AB  - Glucose sensing within autonomic neurocircuits is critical for the effective
      integration and regulation of a variety of physiological homeostatic functions
      including the co-ordination of vagally-mediated reflexes regulating
      gastrointestinal (GI) functions. Glucose regulates GI functions via actions at
      multiple sites of action, from modulating the activity of enteric neurons,
      endocrine cells, and glucose transporters within the intestine, to regulating the
      activity and responsiveness of the peripheral terminals, cell bodies and central
      terminals of vagal sensory neurons, to modifying both the activity and synaptic
      responsiveness of central brainstem neurons. Unsurprisingly, significant
      impairment in GI functions occurs in pathophysiological states where glucose
      levels are dysregulated, such as diabetes. A substantial obstacle to the
      development of new therapies to modify the disease, rather than treat the
      symptoms, are the gaps in our understanding of the mechanisms by which glucose
      modulates GI functions, particularly vagally-mediated responses and a more
      complete understanding of disease-related plasticity within these neurocircuits
      may open new avenues and targets for research. 

PMID- 24324394
TI  - Super-resolution microscopy in studying neuroendocrine cell function.
AB  - The last two decades have seen a tremendous development in high resolution
      microscopy techniques giving rise to acronyms such as TIRFM, SIM, PALM, STORM,
      and STED. The goal of all these techniques is to overcome the physical resolution
      barrier of light microscopy in order to resolve precise protein localization and
      possibly their interaction in cells. Neuroendocrine cell function is to secrete
      hormones and peptides on demand. This fine-tuned multi-step process is mediated
      by a large array of proteins. Here, we review the new microscopy techniques used
      to obtain high resolution and how they have been applied to increase our
      knowledge of the molecular mechanisms involved in neuroendocrine cell secretion.
      Further the limitations of these methods are discussed and insights in possible
      new applications are provided. 

PMID- 24324395
TI  - Lamarckian evolution explains human brain evolution and psychiatric disorders.

PMID- 24324396
TI  - Predeliberation activity in prefrontal cortex and striatum and the prediction of
      subsequent value judgment.
AB  - Rational, value-based decision-making mandates selecting the option with highest
      subjective expected value after appropriate deliberation. We examined activity in
      the dorsolateral prefrontal cortex (DLPFC) and striatum of monkeys deciding
      between smaller, immediate rewards and larger, delayed ones. We previously found
      neurons that modulated their activity in this task according to the animal's
      choice, while it deliberated (choice neurons). Here we found neurons whose
      spiking activities were predictive of the spatial location of the selected target
      (spatial-bias neurons) or the size of the chosen reward (reward-bias neurons)
      before the onset of the cue presenting the decision-alternatives, and thus before
      rational deliberation could begin. Their predictive power increased as the values
      the animals associated with the two decision alternatives became more similar.
      The ventral striatum (VS) preferentially contained spatial-bias neurons; the
      caudate nucleus (CD) preferentially contained choice neurons. In contrast, the
      DLPFC contained significant numbers of all three neuron types, but choice neurons
      were not preferentially also bias neurons of either kind there, nor were spatial
      bias neurons preferentially also choice neurons, and vice versa. We suggest a
      simple winner-take-all (WTA) circuit model to account for the dissociation of
      choice and bias neurons. The model reproduced our results and made additional
      predictions that were borne out empirically. Our data are compatible with the
      hypothesis that the DLPFC and striatum harbor dissociated neural populations that
      represent choices and predeliberation biases that are combined after cue onset;
      the bias neurons have a weaker effect on the ultimate decision than the choice
      neurons, so their influence is progressively apparent for trials where the values
      associated with the decision alternatives are increasingly similar. 

PMID- 24324397
TI  - MicroRNAs as biomarkers for CNS disease.
AB  - For many neurological diseases, the efficacy and outcome of treatment depend on
      early detection. Diagnosis is currently based on the detection of symptoms and
      neuroimaging abnormalities, which appear at relatively late stages in the
      pathogenesis. However, the underlying molecular responses to genetic and
      environmental insults begin much earlier and non-coding RNA networks are
      critically involved in these cellular regulatory mechanisms. Profiling RNA
      expression patterns could thus facilitate presymptomatic disease detection.
      Obtaining indirect readouts of pathological processes is particularly important
      for brain disorders because of the lack of direct access to tissue for molecular
      analyses. Living neurons and other CNS cells secrete microRNA and other small non
      coding RNA into the extracellular space packaged in exosomes, microvesicles, or
      lipoprotein complexes. This discovery, together with the rapidly evolving massive
      sequencing technologies that allow detection of virtually all RNA species from
      small amounts of biological material, has allowed significant progress in the use
      of extracellular RNA as a biomarker for CNS malignancies, neurological, and
      psychiatric diseases. There is also recent evidence that the interactions between
      external stimuli and brain pathological processes may be reflected in peripheral
      tissues, facilitating their use as potential diagnostic markers. In this review,
      we explore the possibilities and challenges of using microRNA and other small
      RNAs as a signature for neurodegenerative and other neuropsychatric conditions. 

PMID- 24324398
TI  - Expression of genes encoding the calcium signalosome in cellular and transgenic
      models of Huntington's disease.
AB  - Huntington's disease (HD) is a hereditary neurodegenerative disease caused by the
      expansion of a polyglutamine stretch in the huntingtin (HTT) protein and
      characterized by dysregulated calcium homeostasis. We investigated whether these
      disturbances are correlated with changes in the mRNA level of the genes that
      encode proteins involved in calcium homeostasis and signaling (i.e., the
      calciosome). Using custom-made TaqMan low-density arrays containing probes for 96
      genes, we quantified mRNA in the striatum in YAC128 mice, a model of HD, and
      wildtype mice. HTT mutation caused the increased expression of some components of
      the calcium signalosome, including calretinin, presenilin 2, and calmyrin 1, and
      the increased expression of genes indirectly involved in calcium homeostasis,
      such as huntingtin-associated protein 1 and calcyclin-binding protein. To verify
      these findings in a different model, we used PC12 cells with an inducible
      expression of mutated full-length HTT. Using single-cell imaging with Fura-2AM,
      we found that store-operated Ca(2+) entry but not endoplasmic reticulum (ER)
      store content was changed as a result of the expression of mutant HTT.
      Statistically significant downregulation of the Orai calcium channel subunit 2,
      calmodulin, and septin 4 was detected in cells that expressed mutated HTT. Our
      data indicate that the dysregulation of calcium homeostasis correlates with
      changes in the gene expression of members of the calciosome. These changes,
      however, differed in the two models of HD used in this study. Our results
      indicate that each HD model exhibits distinct features that may only partially
      resemble the human disease. 

PMID- 24324399
TI  - A comprehensive characterization of the nuclear microRNA repertoire of post
      mitotic neurons.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs with important functions in the
      development and plasticity of post-mitotic neurons. In addition to the well
      described cytoplasmic function of miRNAs in post-transcriptional gene regulation,
      recent studies suggested that miRNAs could also be involved in transcriptional
      and post-transcriptional regulatory processes in the nuclei of proliferating
      cells. However, whether miRNAs localize to and function within the nucleus of
      post-mitotic neurons is unknown. Using a combination of microarray hybridization
      and small RNA deep sequencing, we identified a specific subset of miRNAs which
      are enriched in the nuclei of neurons. Nuclear enrichment of specific candidate
      miRNAs (miR-25 and miR-92a) could be independently validated by Northern blot,
      quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization
      (FISH). By cross-comparison to published reports, we found that nuclear
      accumulation of miRNAs might be linked to a down-regulation of miRNA expression
      during in vitro development of cortical neurons. Importantly, by generating a
      comprehensive isomiR profile of the nuclear and cytoplasmic compartments, we
      found a significant overrepresentation of guanine nucleotides (nt) at the 3'
      terminus of nuclear-enriched isomiRs, suggesting the presence of neuron-specific
      mechanisms involved in miRNA nuclear localization. In conclusion, our results
      provide a starting point for future studies addressing the nuclear function of
      specific miRNAs and the detailed mechanisms underlying subcellular localization
      of miRNAs in neurons and possibly other polarized cell types. 

PMID- 24324400
TI  - Post-translational regulation of P2X receptor channels: modulation by
      phospholipids.
AB  - P2X receptor channels mediate fast excitatory signaling by ATP and play major
      roles in sensory transduction, neuro-immune communication and inflammatory
      response. P2X receptors constitute a gene family of calcium-permeable ATP-gated
      cation channels therefore the regulation of P2X signaling is critical for both
      membrane potential and intracellular calcium homeostasis. Phosphoinositides
      (PIPn) are anionic signaling phospholipids that act as functional regulators of
      many types of ion channels. Direct PIPn binding was demonstrated for several
      ligand- or voltage-gated ion channels, however no generic motif emerged to
      accurately predict lipid-protein binding sites. This review presents what is
      currently known about the modulation of the different P2X subtypes by
      phospholipids and about critical determinants underlying their sensitivity to
      PIPn levels in the plasma membrane. All functional mammalian P2X subtypes tested,
      with the notable exception of P2X5, have been shown to be positively modulated by
      PIPn, i.e., homomeric P2X1, P2X2, P2X3, P2X4, and P2X7, as well as heteromeric
      P2X1/5 and P2X2/3 receptors. Based on various results reported on the
      aforementioned subtypes including mutagenesis of the prototypical PIPn-sensitive
      P2X4 and PIPn-insensitive P2X5 receptor subtypes, an increasing amount of
      functional, biochemical and structural evidence converges on the modulatory role
      of a short polybasic domain located in the proximal C-terminus of P2X subunits.
      This linear motif, semi-conserved in the P2X family, seems necessary and
      sufficient for encoding direct modulation of ATP-gated channels by PIPn.
      Furthermore, the physiological impact of the regulation of ionotropic purinergic
      responses by phospholipids on pain pathways was recently revealed in the context
      of native crosstalks between phospholipase C (PLC)-linked metabotropic receptors
      and P2X receptor channels in dorsal root ganglion sensory neurons and microglia. 

PMID- 24324401
TI  - Neuronal activity in the hub of extrasynaptic Schwann cell-axon interactions.
AB  - The integrity and function of neurons depend on their continuous interactions
      with glial cells. In the peripheral nervous system glial functions are exerted by
      Schwann cells (SCs). SCs sense synaptic and extrasynaptic manifestations of
      action potential propagation and adapt their physiology to support neuronal
      activity. We review here existing literature data on extrasynaptic bidirectional
      axon-SC communication, focusing particularly on neuronal activity implications.
      To shed light on underlying mechanisms, we conduct a thorough analysis of
      microarray data from SC-rich mouse sciatic nerve at different developmental
      stages and in neuropathic models. We identify molecules that are potentially
      involved in SC detection of neuronal activity signals inducing subsequent glial
      responses. We further suggest that alterations in the activity-dependent axon-SC
      crosstalk impact on peripheral neuropathies. Together with previously reported
      data, these observations open new perspectives for deciphering glial mechanisms
      of neuronal function support. 

PMID- 24324402
TI  - Dynamic micro-organization of P2X7 receptors revealed by PALM based single
      particle tracking.
AB  - Adenosine triphosphate (ATP)-gated P2X7 receptors (P2X7Rs) are members of the
      purinergic receptor family that are expressed in several cell types including
      neurons. A high concentration of ATP is required for the channel opening of
      P2X7Rs compared to other members of this receptor family. Recent work suggests
      that ATP binding to members of the P2X receptor family determines the diffusion
      and localization of these receptors on the plasma membrane of neurons. Here, we
      employed single particle tracking photoactivated localization microscopy
      (sptPALM) to study the diffusion and ATP-dependence of rat P2X7Rs. Dendra2-tagged
      P2X7Rs were transfected in hippocampal neurons and imaged on proximal dendrites.
      Our results suggest the presence of two populations of P2X7Rs within the extra
      synaptic membrane: a population composed of rapidly diffusing receptors and one
      stabilized within nanoclusters (~100 nm diameter). P2X7R trajectories were rarely
      observed at synaptic sites. P2X7R mutations in the ATP-binding site (K64A) or the
      conserved phosphorylation site (K17A) resulted in faster- and slower-diffusing
      receptors, respectively. Furthermore, ATP differentially accelerated wild type
      and K17A-mutant receptors but not K64A-mutant receptors. Our results indicate
      that receptor conformation plays a critical role in regulating ATP-mediated
      changes in P2X7R diffusion and micro-organization. 

PMID- 24324403
TI  - Differential autophagy power in the spinal cord and muscle of transgenic ALS
      mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a motoneuron disease characterized by
      misfolded proteins aggregation in affected motoneurons. In mutant SOD1 (mutSOD1)
      ALS models, aggregation correlates to impaired functions of proteasome and/or
      autophagy, both essential for the intracellular chaperone-mediated protein
      quality control (PQC), and to a reduced mutSOD1 clearance from motoneurons.
      Skeletal muscle cells are also sensitive to mutSOD1 toxicity, but no mutSOD1
      aggregates are formed in these cells, that might better manage mutSOD1 than
      motoneurons. Thus, we analyzed in spinal cord and in muscle of transgenic (tg)
      G93A-SOD1 mice at presymptomatic (PS, 8 weeks) and symptomatic (S, 16 weeks)
      stages, and in age-matched control mice, whether mutSOD1 differentially modulates
      relevant PQC players, such as HSPB8, BAG3, and BAG1. Possible sex differences
      were also considered. No changes of HSPB8, BAG3, and BAG1 at PS stage (8 weeks)
      were seen in all tissues examined in tg G93A-SOD1 and control mice. At S stage
      (16 weeks), HSPB8 dramatically increased in skeletal muscle of tg G93A-SOD1 mice,
      while a minor increase occurred in spinal cord of male, but not female tg G93A
      SOD1 mice. BAG3 expression increased both in muscle and spinal cord of tg G93A
      SOD1 mice at S stage, BAG1 expression increased only in muscle of the same mice.
      Since, HSPB8-BAG3 complex assists mutSOD1 autophagic removal, we analyzed two
      well-known autophagic markers, LC3 and p62. Both LC3 and p62 mRNAs were
      significantly up-regulated in skeletal muscle of tg G93A-SOD1 mice at S stage (16
      weeks). This suggests that mutSOD1 expression induces a robust autophagic
      response specifically in muscle. Together these results demonstrate that, in
      muscle mutSOD1-induced autophagic response is much higher than in spinal cord. In
      addition, if mutSOD1 exerts toxicity in muscle, this may not be mediated by
      misfolded proteins accumulation. It remains unclear whether in muscle mutSOD1
      toxicity is related to aberrant autophagy activation. 

PMID- 24324404
TI  - P2X receptors as targets for the treatment of status epilepticus.
AB  - Prolonged seizures are amongst the most common neurological emergencies. Status
      epilepticus is a state of continuous seizures that is life-threatening and prompt
      termination of status epilepticus is critical to protect the brain from permanent
      damage. Frontline treatment comprises parenteral administration of
      anticonvulsants such as lorazepam that facilitate gamma-amino butyric acid (GABA)
      transmission. Because status epilepticus can become refractory to anticonvulsants
      in a significant proportion of patients, drugs which act on different
      neurotransmitter systems may represent potential adjunctive treatments. P2X
      receptors are a class of ligand-gated ion channel activated by ATP that
      contributes to neuro- and glio-transmission. P2X receptors are expressed by both
      neurons and glia in various brain regions, including the hippocampus.
      Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors
      are activated during pathologic brain activity. Expression of several members of
      the family including P2X2, P2X4, and P2X7 receptors has been reported to be
      altered in the hippocampus following status epilepticus. Recent studies have
      shown that ligands of the P2X7 receptor can have potent effects on seizure
      severity during status epilepticus and mice lacking this receptor display altered
      seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also
      modulate neuronal death, microglial responses and neuroinflammatory signaling.
      Recent work also found altered neuronal injury and inflammation after status
      epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X
      receptor family may serve important roles in the pathophysiology of status
      epilepticus and represent novel targets for seizure control and neuroprotection. 

PMID- 24324405
TI  - Next-generation transgenic mice for optogenetic analysis of neural circuits.
AB  - Here we characterize several new lines of transgenic mice useful for optogenetic
      analysis of brain circuit function. These mice express optogenetic probes, such
      as enhanced halorhodopsin or several different versions of channelrhodopsins,
      behind various neuron-specific promoters. These mice permit photoinhibition or
      photostimulation both in vitro and in vivo. Our results also reveal the important
      influence of fluorescent tags on optogenetic probe expression and function in
      transgenic mice. 

PMID- 24324406
TI  - Distinct roles of synaptic and extrasynaptic GABAAreceptors in striatal
      inhibition dynamics.
AB  - Striatonigral and striatopallidal projecting medium spiny neurons (MSNs) express
      dopamine D1 (D1+) and D2 receptors (D2+), respectively. Both classes receive
      extensive GABAergic input via expression of synaptic, perisynaptic, and
      extrasynaptic GABAA receptors. The activation patterns of different presynaptic
      GABAergic neurons produce transient and sustained GABAA receptor-mediated
      conductance that fulfill distinct physiological roles. We performed single and
      dual whole cell recordings from striatal neurons in mice expressing fluorescent
      proteins in interneurons and MSNs. We report specific inhibitory dynamics
      produced by distinct activation patterns of presynaptic GABAergic neurons as
      source of synaptic, perisynaptic, and extrasynaptic inhibition. Synaptic GABAA
      receptors in MSNs contain the alpha2, gamma2, and a beta subunit. In addition,
      there is evidence for the developmental increase of the alpha1 subunit that
      contributes to faster inhibitory post-synaptic current (IPSC). Tonic GABAergic
      currents in MSNs from adult mice are carried by extrasynaptic receptors
      containing the alpha4 and delta subunit, while in younger mice this current is
      mediated by receptors that contain the alpha5 subunit. Both forms of tonic
      currents are differentially expressed in D1+ and D2+ MSNs. This study extends
      these findings by relating presynaptic activation with pharmacological analysis
      of inhibitory conductance in mice where the beta3 subunit is conditionally
      removed in fluorescently labeled D2+ MSNs and in mice with global deletion of the
      delta subunit. Our results show that responses to low doses of gaboxadol (2 MUM),
      a GABAA receptor agonist with preference to delta subunit, are abolished in the
      delta but not the beta3 subunit knock out mice. This suggests that the beta3
      subunit is not a component of the adult extrasynaptic receptor pool, in contrast
      to what has been shown for tonic current in young mice. Deletion of the beta3
      subunit from D2+ MSNs however, removed slow spontaneous IPSCs, implicating its
      role in mediating synaptic input from striatal neurogliaform interneurons. 

PMID- 24324407
TI  - Reduced tonic inhibition in striatal output neurons from Huntington mice due to
      loss of astrocytic GABA release through GAT-3.
AB  - The extracellular concentration of the two main neurotransmitters glutamate and
      GABA is low but not negligible which enables a number of tonic actions. The
      effects of ambient GABA vary in a region-, cell-type, and age-dependent manner
      and can serve as indicators of disease-related alterations. Here we explored the
      tonic inhibitory actions of GABA in Huntington's disease (HD). HD is a
      devastating neurodegenerative disorder caused by a mutation in the huntingtin
      gene. Whole cell patch clamp recordings from striatal output neurons (SONs) in
      slices from adult wild type mice and two mouse models of HD (Z_Q175_KI
      homozygotes or R6/2 heterozygotes) revealed an HD-related reduction of the
      GABA(A) receptor-mediated tonic chloride current (I(Tonic(GABA))) along with
      signs of reduced GABA(B) receptor-mediated presynaptic depression of synaptic
      GABA release. About half of I(Tonic(GABA)) depended on tetrodotoxin-sensitive
      synaptic GABA release, but the remaining current was still lower in HD. Both in
      WT and HD, I(Tonic(GABA)) was more prominent during the first 4 h after preparing
      the slices, when astrocytes but not neurons exhibited a transient depolarization.
      All further tests were performed within 1-4 h in vitro. Experiments with
      SNAP5114, a blocker of the astrocytic GABA transporter GAT-3, suggest that in WT
      but not HD GAT-3 operated in the releasing mode. Application of a transportable
      substrate for glutamate transporters (D-aspartate 0.1-1 mM) restored the non
      synaptic GABA release in slices from HD mice. I(Tonic(GABA)) was also rescued by
      applying the hyperagonist gaboxadol (0.33 MUM). The results lead to the
      hypothesis that lesion-induced astrocyte depolarization facilitates non-synaptic
      release of GABA through GAT-3. However, the capacity of depolarized astrocytes to
      provide GABA for tonic inhibition is strongly reduced in HD.

PMID- 24324408
TI  - Primate cerebellar granule cells exhibit a tonic GABAAR conductance that is not
      affected by alcohol: a possible cellular substrate of the low level of response
      phenotype.
AB  - In many rodent brain regions, alcohol increases vesicular release of GABA,
      resulting in an increase in the frequency of spontaneous inhibitory postsynaptic
      currents (sIPSCs) and the magnitude of tonic GABAA receptor (GABAAR) currents. A
      neglected issue in translating the rodent literature to humans is the possibility
      that phylogenetic differences alter the actions of alcohol. To address this issue
      we made voltage-clamp recordings from granule cells (GCs) in cerebellar slices
      from the non-human primate (NHP), Macaca fascicularis. We found that similar to
      Sprague Dawley rats (SDRs), NHP GCs exhibit a tonic conductance generated by
      alpha6delta subunit containing GABAARs, as evidenced by its blockade by the broad
      spectrum GABAAR antagonist, GABAzine (10 MUM), inhibition by alpha6 selective
      antagonist, furosemide (100 MUM), and enhancement by THDOC (10-20 nM) and THIP
      (500 nM). In contrast to SDR GCs, in most NHP GCs (~60%), application of EtOH (25
      105 mM) did not increase sIPSC frequency or the tonic GABAAR current. In a
      minority of cells (~40%), EtOH did increase sIPSC frequency and the tonic
      current. The relative lack of response to EtOH was associated with reduced
      expression of neuronal nitric oxide synthase (nNOS), which we recently reported
      mediates EtOH-induced enhancement of vesicular GABA release in rats. The EtOH
      induced increase in tonic GABAAR current was significantly smaller in NHPs than
      in SDRs, presumably due to less GABA release, because there were no obvious
      differences in the density of GABAARs or GABA transporters between SDR and NHP
      GCs. Thus, EtOH does not directly modulate alpha6delta subunit GABAARs in NHPs.
      Instead, EtOH enhanced GABAergic transmission is mediated by enhanced GABA
      release. Further, SDR GC responses to alcohol are only representative of a
      subpopulation of NHP GCs. This suggests that the impact of EtOH on NHP cerebellar
      physiology will be reduced compared to SDRs, and will likely have different
      computational and behavioral consequences. 

PMID- 24324410
TI  - Non-invasive brain stimulation for the treatment of brain diseases in childhood
      and adolescence: state of the art, current limits and future challenges.
AB  - In the last decades interest in application of non-invasive brain stimulation for
      enhancing neural functions is growing continuously. However, the use of such
      techniques in pediatric populations remains rather limited and mainly confined to
      the treatment of severe neurological and psychiatric diseases. In this article we
      provide a complete review of non-invasive brain stimulation studies conducted in
      pediatric populations. We also provide a brief discussion about the current
      limitations and future directions in a field of research still very young and
      full of issues to be explored. 

PMID- 24324409
TI  - Functional and structural changes throughout the auditory system following
      congenital and early-onset deafness: implications for hearing restoration.
AB  - The absence of auditory input, particularly during development, causes widespread
      changes in the structure and function of the auditory system, extending from
      peripheral structures into auditory cortex. In humans, the consequences of these
      changes are far-reaching and often include detriments to language acquisition,
      and associated psychosocial issues. Much of what is currently known about the
      nature of deafness-related changes to auditory structures comes from studies of
      congenitally deaf or early-deafened animal models. Fortunately, the mammalian
      auditory system shows a high degree of preservation among species, allowing for
      generalization from these models to the human auditory system. This review begins
      with a comparison of common methods used to obtain deaf animal models,
      highlighting the specific advantages and anatomical consequences of each. Some
      consideration is also given to the effectiveness of methods used to measure
      hearing loss during and following deafening procedures. The structural and
      functional consequences of congenital and early-onset deafness have been examined
      across a variety of mammals. This review attempts to summarize these changes,
      which often involve alteration of hair cells and supporting cells in the
      cochleae, and anatomical and physiological changes that extend through
      subcortical structures and into cortex. The nature of these changes is discussed,
      and the impacts to neural processing are addressed. Finally, long-term changes in
      cortical structures are discussed, with a focus on the presence or absence of
      cross-modal plasticity. In addition to being of interest to our understanding of
      multisensory processing, these changes also have important implications for the
      use of assistive devices such as cochlear implants. 

PMID- 24324411
TI  - Seeing the talker's face supports executive processing of speech in steady state
      noise.
AB  - Listening to speech in noise depletes cognitive resources, affecting speech
      processing. The present study investigated how remaining resources or cognitive
      spare capacity (CSC) can be deployed by young adults with normal hearing. We
      administered a test of CSC (CSCT; Mishra et al., 2013) along with a battery of
      established cognitive tests to 20 participants with normal hearing. In the CSCT,
      lists of two-digit numbers were presented with and without visual cues in quiet,
      as well as in steady-state and speech-like noise at a high intelligibility level.
      In low load conditions, two numbers were recalled according to instructions
      inducing executive processing (updating, inhibition) and in high load conditions
      the participants were additionally instructed to recall one extra number, which
      was the always the first item in the list. In line with previous findings,
      results showed that CSC was sensitive to memory load and executive function but
      generally not related to working memory capacity (WMC). Furthermore, CSCT scores
      in quiet were lowered by visual cues, probably due to distraction. In steady
      state noise, the presence of visual cues improved CSCT scores, probably by
      enabling better encoding. Contrary to our expectation, CSCT performance was
      disrupted more in steady-state than speech-like noise, although only without
      visual cues, possibly because selective attention could be used to ignore the
      speech-like background and provide an enriched representation of target items in
      working memory similar to that obtained in quiet. This interpretation is
      supported by a consistent association between CSCT scores and updating skills. 

PMID- 24324412
TI  - Primary motor cortex of the parkinsonian monkey: altered neuronal responses to
      muscle stretch.
AB  - Exaggeration of the long-latency stretch reflex (LLSR) is a characteristic
      neurophysiologic feature of Parkinson's disease (PD) that contributes to
      parkinsonian rigidity. To explore one frequently-hypothesized mechanism, we
      studied the effects of fast muscle stretches on neuronal activity in the macaque
      primary motor cortex (M1) before and after the induction of parkinsonism by
      unilateral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
      We compared results from the general population of M1 neurons and two
      antidromically-identified subpopulations: distant-projecting pyramidal-tract type
      neurons (PTNs) and intra-telecenphalic-type corticostriatal neurons (CSNs). Rapid
      rotations of elbow or wrist joints evoked short-latency responses in 62% of arm
      related M1 neurons. As in PD, the late electromyographic responses that
      constitute the LLSR were enhanced following MPTP. This was accompanied by a
      shortening of M1 neuronal response latencies and a degradation of directional
      selectivity, but surprisingly, no increase in single unit response magnitudes.
      The results suggest that parkinsonism alters the timing and specificity of M1
      responses to muscle stretch. Observation of an exaggerated LLSR with no change in
      the magnitude of proprioceptive responses in M1 is consistent with the idea that
      the increase in LLSR gain that contributes to parkinsonian rigidity is localized
      to the spinal cord. 

PMID- 24324414
TI  - Functional testing in animal models of spinal cord injury: not as straight
      forward as one would think.
AB  - When exploring potential treatments for spinal cord injury (SCI), functional
      recovery is deemed the most relevant outcome measure when it comes to
      translational considerations. Yet, assessing such recovery and potential
      treatment effects is challenging and the pitfalls are frequently underestimated.
      The consequences are that in many cases positive results cannot be reliably
      replicated, and likely treatments that appear to lack effects have been dismissed
      prematurely. In this article we review the relationships between lesion
      location/severity and functional outcomes with specific consideration given to
      floor and ceiling effects. The roles of compensatory strategies, the challenges
      of distinguishing them from bona fide recovery, and of comparing function to pre
      injury levels given the variability inherent in animal testing are discussed.
      Ultimately, we offer a series of considerations to enhance the power of
      functional analysis in animal models of SCI. 

PMID- 24324413
TI  - From ear to uncertainty: vestibular contributions to cognitive function.
AB  - In addition to the deficits in the vestibulo-ocular and vestibulo-spinal reflexes
      that occur following vestibular dysfunction, there is substantial evidence that
      vestibular loss also causes cognitive disorders, some of which may be due to the
      reflexive deficits and some of which are related to the role that ascending
      vestibular pathways to the limbic system and neocortex play in spatial
      orientation. In this review we summarize the evidence that vestibular loss causes
      cognitive disorders, especially spatial memory deficits, in animals and humans
      and critically evaluate the evidence that these deficits are not due to hearing
      loss, problems with motor control, oscillopsia or anxiety and depression. We
      review the evidence that vestibular lesions affect head direction and place cells
      as well as the emerging evidence that artificial activation of the vestibular
      system, using galvanic vestibular stimulation (GVS), can modulate cognitive
      function. 

PMID- 24324415
TI  - Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic
      patterns of dopamine transmission reduce ethanol self-administration.
AB  - There is compelling evidence that acute ethanol exposure stimulates ventral
      tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine
      release in terminal fields within the nucleus accumbens plays an integral role in
      the regulation of ethanol drinking behaviors. Unfortunately, due to technical
      limitations, the specific temporal dynamics linking VTA dopamine cell activation
      and ethanol self-administration are not known. In fact, establishing a causal
      link between specific patterns of dopamine transmission and ethanol drinking
      behaviors has proven elusive. Here, we sought to address these gaps in our
      knowledge using a newly developed viral-mediated gene delivery strategy to
      selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of
      wild-type rats. We then used this approach to precisely control VTA dopamine
      transmission during voluntary ethanol drinking sessions. The results confirmed
      that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue
      light pulses to the VTA induced dopamine release in accumbal terminal fields with
      very high temporal and spatial precision. Brief high frequency VTA stimulation
      induced phasic patterns of dopamine release in the nucleus accumbens. Lower
      frequency stimulation, applied for longer periods mimicked tonic increases in
      accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an
      intermittent ethanol drinking procedure, we found that tonic, but not phasic,
      stimulation of VTA dopamine cells selectively attenuated ethanol drinking
      behaviors. Collectively, these data demonstrate the effectiveness of a novel
      viral targeting strategy that can be used to restrict opsin expression to
      dopamine cells in standard outbred animals and provide the first causal evidence
      demonstrating that tonic activation of VTA dopamine neurons selectively decreases
      ethanol self-administration behaviors. 

PMID- 24324416
TI  - Rodent models of Parkinson's disease: beyond the motor symptomatology.
AB  - Parkinson's disease (PD) is classically characterized by motor symptoms; however,
      non-motor symptoms (NMS) are increasingly recognized as relevant in disease
      state, given the associated alterations in mood (depression and anxiety) and
      cognition. Here, particularly in regards to NMS, we aimed to compare the motor,
      emotional and cognitive behavior of three animal models of PD that trigger
      dopaminergic (DAergic) degeneration on both brain hemispheres: (i) the 6
      hydroxydopamine (6-OHDA, 8 or 6 MUg) lesion model; (ii) the paraquat (PQ) induced
      model, and (iii) a genetic model based on alpha-synuclein overexpression (alpha
      syn). 6-OHDA and alpha-syn vector were injected bilaterally in the substantia
      nigra pars compacta (SNpc) of adult male Wistar rats; as for PQ delivery, micro
      osmotic pumps were implanted in the interscapular region. Motor deficits were
      observed in all models, with histological analysis of tyrosine hydroxylase
      positive cells in the SNpc revealing a significant loss of DAergic neurons in all
      animal models. In addition, the alpha-syn animal model also presented a reduction
      in exploratory activity, and the 6-OHDA and PQ animals displayed a significant
      increase in both depressive- and anxiety-like behavior. Interestingly, cognitive
      impairment (working memory) was only observed in the 6-OHDA model. Overall, these
      PD models are suitable for mimicking the motor symptoms associated to PD, with
      each encompassing other relevant NMS components of the disorder that may prove
      beneficial for further studies in PD. 

PMID- 24324417
TI  - Development of an aversive Pavlovian-to-instrumental transfer task in rat.
AB  - Pavlovian-to-instrumental transfer (PIT) is an effect whereby a classically
      conditioned stimulus (CS) enhances ongoing instrumental responding. PIT has been
      extensively studied with appetitive conditioning but barely at all with aversive
      conditioning. Although it's been argued that conditioned suppression is a form of
      aversive PIT, this effect is fundamentally different from appetitive PIT because
      the CS suppresses, instead of facilitates, responding. Five experiments
      investigated the importance of a variety of factors on aversive PIT in a rodent
      Sidman avoidance paradigm in which ongoing shuttling behavior (unsignaled active
      avoidance or USAA) was facilitated by an aversive CS. Experiment 1 demonstrated a
      basic PIT effect. Experiment 2 found that a moderate amount of USAA extinction
      produces the strongest PIT with shuttling rates best at around 2 responses per
      minute prior to the CS. Experiment 3 tested a protocol in which the USAA behavior
      was required to reach the 2-response per minute mark in order to trigger the CS
      presentation and found that this produced robust and reliable PIT. Experiment 4
      found that the Pavlovian conditioning US intensity was not a major determinant of
      PIT strength. Experiment 5 demonstrated that if the CS and US were not explicitly
      paired during Pavlovian conditioning, PIT did not occur, showing that CS-US
      learning is required. Together, these studies demonstrate a robust, reliable and
      stable aversive PIT effect that is amenable to analysis of neural circuitry. 

PMID- 24324418
TI  - Simulating real world functioning in schizophrenia using a naturalistic city
      environment and single-trial, goal-directed navigation.
AB  - OBJECTIVE: To develop a virtual reality platform that would serve as a
      functionally meaningful measure of cognition in schizophrenia and that would also
      complement standard batteries of cognitive tests during clinical trials for
      cognitive treatments in schizophrenia, be amenable to human neuroimaging
      research, yet lend itself to neurobiological comparison with rodent analogs.
      METHOD: Thirty-three patients with schizophrenia and 33 healthy controls matched
      for age, sex, video gaming experience, and education completed eight rapid,
      single-trial virtual navigation tasks within a naturalistic virtual city. Four
      trials tested their ability to find different targets seen during the passive
      viewing of a closed path that led them around different city blocks. Four
      subsequent trials tested their ability to return to four different starting
      points after viewing a path that took them several blocks away from the starting
      position. RESULTS: Individuals with schizophrenia had difficulties in way
      finding, measured as distance travelled to find targets previously encountered
      within the virtual city. They were also more likely not to notice the target
      during passive viewing, less likely to find novel shortcuts to targets, and more
      likely to become lost and fail completely in finding the target. Total travel
      distances across all eight trials strongly correlated (negatively) with
      neurocognitive measures and, for 49 participants who completed the Quality of
      Life Scale, psychosocial functioning. CONCLUSION: Single-trial, goal-directed
      navigation in a naturalistic virtual environment is a functionally meaningful
      measure of cognitive functioning in schizophrenia.

PMID- 24324419
TI  - Dorsomedial prefrontal cortex activity predicts the accuracy in estimating
      others' preferences.
AB  - The ability to accurately estimate another person's preferences is crucial for a
      successful social life. In daily interactions, we often do this on the basis of
      minimal information. The aims of the present study were (a) to examine whether
      people can accurately judge others based only on a brief exposure to their
      appearances, and (b) to reveal the underlying neural mechanisms with functional
      magnetic resonance imaging (fMRI). Participants were asked to make guesses about
      unfamiliar target individuals' preferences for various items after looking at
      their faces for 3 s. The behavioral results showed that participants estimated
      others' preferences above chance level. The fMRI data revealed that higher
      accuracy in preference estimation was associated with greater activity in the
      dorsomedial prefrontal cortex (DMPFC) when participants were guessing the
      targets' preferences relative to thinking about their own preferences. These
      findings suggest that accurate estimations of others' preferences may require
      increased activity in the DMPFC. A functional connectivity analysis revealed that
      higher accuracy in preference estimation was related to increased functional
      connectivity between the DMPFC and the brain regions that are known to be
      involved in theory of mind processing, such as the temporoparietal junction (TPJ)
      and the posterior cingulate cortex (PCC)/precuneus, during correct vs. incorrect
      guessing trials. On the contrary, the tendency to refer to self-preferences when
      estimating others' preference was related to greater activity in the ventromedial
      prefrontal cortex. These findings imply that the DMPFC may be a core region in
      estimating the preferences of others and that higher accuracy may require
      stronger communication between the DMPFC and the TPJ and PCC/precuneus, part of a
      neural network known to be engaged in mentalizing. 

PMID- 24324420
TI  - Situating emotional experience.
AB  - Psychological construction approaches to emotion suggest that emotional
      experience is situated and dynamic. Fear, for example, is typically studied in a
      physical danger context (e.g., threatening snake), but in the real world, it
      often occurs in social contexts, especially those involving social evaluation
      (e.g., public speaking). Understanding situated emotional experience is critical
      because adaptive responding is guided by situational context (e.g., inferring the
      intention of another in a social evaluation situation vs. monitoring the
      environment in a physical danger situation). In an fMRI study, we assessed
      situated emotional experience using a newly developed paradigm in which
      participants vividly imagine different scenarios from a first-person perspective,
      in this case scenarios involving either social evaluation or physical danger. We
      hypothesized that distributed neural patterns would underlie immersion in social
      evaluation and physical danger situations, with shared activity patterns across
      both situations in multiple sensory modalities and in circuitry involved in
      integrating salient sensory information, and with unique activity patterns for
      each situation type in coordinated large-scale networks that reflect situated
      responding. More specifically, we predicted that networks underlying the social
      inference and mentalizing involved in responding to a social threat (in regions
      that make up the "default mode" network) would be reliably more active during
      social evaluation situations. In contrast, networks underlying the visuospatial
      attention and action planning involved in responding to a physical threat would
      be reliably more active during physical danger situations. The results supported
      these hypotheses. In line with emerging psychological construction approaches,
      the findings suggest that coordinated brain networks offer a systematic way to
      interpret the distributed patterns that underlie the diverse situational contexts
      characterizing emotional life. 

PMID- 24324421
TI  - The Harvard Beat Assessment Test (H-BAT): a battery for assessing beat perception
      and production and their dissociation.
AB  - Humans have the abilities to perceive, produce, and synchronize with a musical
      beat, yet there are widespread individual differences. To investigate these
      abilities and to determine if a dissociation between beat perception and
      production exists, we developed the Harvard Beat Assessment Test (H-BAT), a new
      battery that assesses beat perception and production abilities. H-BAT consists of
      four subtests: (1) music tapping test (MTT), (2) beat saliency test (BST), (3)
      beat interval test (BIT), and (4) beat finding and interval test (BFIT). MTT
      measures the degree of tapping synchronization with the beat of music, whereas
      BST, BIT, and BFIT measure perception and production thresholds via
      psychophysical adaptive stair-case methods. We administered the H-BAT on thirty
      individuals and investigated the performance distribution across these
      individuals in each subtest. There was a wide distribution in individual
      abilities to tap in synchrony with the beat of music during the MTT. The degree
      of synchronization consistency was negatively correlated with thresholds in the
      BST, BIT, and BFIT: a lower degree of synchronization was associated with higher
      perception and production thresholds. H-BAT can be a useful tool in determining
      an individual's ability to perceive and produce a beat within a single session. 

PMID- 24324422
TI  - Impaired mental rotation in benign paroxysmal positional vertigo and acute
      vestibular neuritis.
AB  - Vestibular processing is fundamental to our sense of orientation in space which
      is a core aspect of the representation of the self. Vestibular information is
      processed in a large subcortical-cortical neural network. Tasks requiring mental
      rotations of human bodies in space are known to activate neural regions within
      this network suggesting that vestibular processing is involved in the control of
      mental rotation. We studied whether mental rotation is impaired in patients
      suffering from two different forms of unilateral vestibular disorders (vestibular
      neuritis - VN - and Benign Paroxysmal positional Vertigo - BPPV) with respect to
      healthy matched controls (C). We used two mental rotation tasks in which
      participants were required to: (i) mentally rotate their own body in space
      (egocentric rotation) thus using vestibular processing to a large extent and (ii)
      mentally rotate human figures (allocentric rotation) thus using own body
      representations to a smaller degree. Reaction times and accuracy of responses
      showed that VN and BPPV patients were impaired in both tasks with respect to C.
      Significantly, the pattern of results was similar in the three groups suggesting
      that patients were actually performing the mental rotation without using a
      different strategy from the control individuals. These results show that
      dysfunctional vestibular inflow impairs mental rotation of both own body and
      human figures suggesting that unilateral acute disorders of the peripheral
      vestibular input massively affect the cerebral processes underlying mental
      rotations. 

PMID- 24324423
TI  - Does that look heavy to you? Perceived weight judgment in lifting actions in
      younger and older adults.
AB  - When interpreting other people's movements or actions, observers may not only
      rely on the visual cues available in the observed movement, but they may also be
      able to "put themselves in the other person's shoes" by engaging brain systems
      involved in both "mentalizing" and motor simulation. The ageing process brings
      changes in both perceptual and motor abilities, yet little is known about how
      these changes may affect the ability to accurately interpret other people's
      actions. Here we investigated the effect of ageing on the ability to discriminate
      the weight of objects based on the movements of actors lifting these objects.
      Stimuli consisted of videos of an actor lifting a small box weighing 0.05-0.9 kg
      or a large box weighting 3-18 kg. In a four-alternative forced-choice task,
      younger and older participants reported the perceived weight of the box in each
      video. Overall, older participants were less sensitive than younger participants
      in discriminating the perceived weight of lifted boxes, an effect that was
      especially pronounced in the small box condition. Weight discrimination
      performance was better for the large box compared to the small box in both
      groups, due to greater saliency of the visual cues in this condition. These
      results suggest that older adults may require more salient visual cues to
      interpret the actions of others accurately. We discuss the potential contribution
      of age-related changes in visual and motor function on the observed effects and
      suggest that older adults' decline in the sensitivity to subtle visual cues may
      lead to greater reliance on visual analysis of the observed scene and its
      semantic context. 

PMID- 24324424
TI  - Trisecting representational states in short-term memory.
AB  - The ability to hold information briefly in mind in the absence of external
      stimulation forms the core of much of higher-order cognition. This ability is
      referred to as short-term memory (STM). However, single-term labels such as this
      belie the complexity of the underlying construct. Here, we review evidence that
      STM is an amalgamation of three qualitatively distinct states. We argue that
      these distinct states emerge from the combination of frontal selection mechanisms
      (often considered the domain of attention and cognitive control), medial temporal
      binding mechanisms (often considered the domain of long-term memory, LTM), and
      synaptic plasticity. These various contributions lead to a single representation
      amenable to elaborated processing (focus of attention), a limited set of active
      representations among which attention can be flexibly switched (direct-access
      region), and passive representations whose residual traces facilitate re
      activation (activated LTM). We suggest that selection and binding mechanisms are
      typically engaged simultaneously, providing multiple forms and routes of short
      term maintenance. We propose that such a framework can resolve discrepancies
      among recent studies that have attempted to understand the relationship between
      attention and STM on the one hand, and between LTM and STM on the other. We
      anticipate that recent advances in neuroimaging and neurophysiology will
      elucidate the mechanisms underlying shifts and transformations among these
      representational states, providing a window into the dynamic processes of higher
      order cognition. 

PMID- 24324425
TI  - Shared action spaces: a basis function framework for social re-calibration of
      sensorimotor representations supporting joint action.
AB  - The article explores the possibilities of formalizing and explaining the
      mechanisms that support spatial and social perspective alignment sustained over
      the duration of a social interaction. The basic proposed principle is that in
      social contexts the mechanisms for sensorimotor transformations and multisensory
      integration (learn to) incorporate information relative to the other actor(s),
      similar to the "re-calibration" of visual receptive fields in response to
      repeated tool use. This process aligns or merges the co-actors' spatial
      representations and creates a "Shared Action Space" (SAS) supporting key
      computations of social interactions and joint actions; for example, the remapping
      between the coordinate systems and frames of reference of the co-actors,
      including perspective taking, the sensorimotor transformations required for
      lifting jointly an object, and the predictions of the sensory effects of such
      joint action. The social re-calibration is proposed to be based on common basis
      function maps (BFMs) and could constitute an optimal solution to sensorimotor
      transformation and multisensory integration in joint action or more in general
      social interaction contexts. However, certain situations such as discrepant
      postural and viewpoint alignment and associated differences in perspectives
      between the co-actors could constrain the process quite differently. We discuss
      how alignment is achieved in the first place, and how it is maintained over time,
      providing a taxonomy of various forms and mechanisms of space alignment and
      overlap based, for instance, on automaticity vs. control of the transformations
      between the two agents. Finally, we discuss the link between low-level mechanisms
      for the sharing of space and high-level mechanisms for the sharing of cognitive
      representations. 

PMID- 24324426
TI  - Long-range neural activity evoked by premotor cortex stimulation: a TMS/EEG co
      registration study.
AB  - The premotor cortex is one of the fundamental structures composing the neural
      networks of the human brain. It is implicated in many behaviors and cognitive
      tasks, ranging from movement to attention and eye-related activity. Therefore,
      neural circuits that are related to premotor cortex have been studied to clarify
      their connectivity and/or role in different tasks. In the present work, we aimed
      to investigate the propagation of the neural activity evoked in the dorsal
      premotor cortex using transcranial magnetic stimulation/electroencephalography
      (TMS/EEG). Toward this end, interest was focused on the neural dynamics elicited
      in long-ranging temporal and spatial networks. Twelve healthy volunteers
      underwent a single-pulse TMS protocol in a resting condition with eyes closed,
      and the evoked activity, measured by EEG, was compared to a sham condition in a
      time window ranging from 45 ms to about 200 ms after TMS. Spatial and temporal
      investigations were carried out with sLORETA. TMS was found to induce propagation
      of neural activity mainly in the contralateral sensorimotor and frontal cortices,
      at about 130 ms after delivery of the stimulus. Different types of analyses
      showed propagated activity also in posterior, mainly visual, regions, in a time
      window between 70 and 130 ms. Finally, a likely "rebounding" activation of the
      sensorimotor and frontal regions, was observed in various time ranges. Taken
      together, the present findings further characterize the neural circuits that are
      driven by dorsal premotor cortex activation in healthy humans. 

PMID- 24324427
TI  - Rational design of transcranial current stimulation (TCS) through mechanistic
      insights into cortical network dynamics.
AB  - Transcranial current stimulation (TCS) is a promising method of non-invasive
      brain stimulation to modulate cortical network dynamics. Preliminary studies have
      demonstrated the ability of TCS to enhance cognition and reduce symptoms in both
      neurological and psychiatric illnesses. Despite the encouraging results of these
      studies, the mechanisms by which TCS and endogenous network dynamics interact
      remain poorly understood. Here, we propose that the development of the next
      generation of TCS paradigms with increased efficacy requires such mechanistic
      understanding of how weak electric fields (EFs) imposed by TCS interact with the
      nonlinear dynamics of large-scale cortical networks. We highlight key recent
      advances in the study of the interaction dynamics between TCS and cortical
      network activity. In particular, we illustrate an interdisciplinary approach that
      bridges neurobiology and electrical engineering. We discuss the use of (1) hybrid
      biological-electronic experimental approaches to disentangle feedback
      interactions; (2) large-scale computer simulations for the study of weak global
      perturbations imposed by TCS; and (3) optogenetic manipulations informed by
      dynamic systems theory to probe network dynamics. Together, we here provide the
      foundation for the use of rational design for the development of the next
      generation of TCS neurotherapeutics. 

PMID- 24324429
TI  - Attention shifts the language network reflecting paradigm presentation.
AB  - OBJECTIVES: Functional magnetic resonance imaging (fMRI) is a reliable and non
      invasive method with which to localize language function in pre-surgical
      planning. In clinical practice, visual stimulus presentation is often difficult
      or impossible, due to the patient's restricted language or attention abilities.
      Therefore, our aim was to investigate modality-specific differences in visual and
      auditory stimulus presentation. METHODS: Ten healthy subjects participated in an
      fMRI study comprising two experiments with visual and auditory stimulus
      presentation. In both experiments, two language paradigms (one for language
      comprehension and one for language production) used in clinical practice were
      investigated. In addition to standard data analysis by the means of the general
      linear model (GLM), independent component analysis (ICA) was performed to achieve
      more detailed information on language processing networks. RESULTS: GLM analysis
      revealed modality-specific brain activation for both language paradigms for the
      contrast visual > auditory in the area of the intraparietal sulcus and the
      hippocampus, two areas related to attention and working memory. Using group ICA,
      a language network was detected for both paradigms independent of stimulus
      presentation modality. The investigation of language lateralization revealed no
      significant variations. Visually presented stimuli further activated an attention
      shift network, which could not be identified for the auditory presented language.
      CONCLUSION: The results of this study indicate that the visually presented
      language stimuli additionally activate an attention-shift network. These findings
      will provide important information for pre-surgical planning in order to preserve
      reading abilities after brain surgery, significantly improving surgical outcomes.
      Our findings suggest that the presentation modality for language paradigms should
      be adapted on behalf of individual indication.

PMID- 24324428
TI  - Multiple roles of motor imagery during action observation.
AB  - Over the last 20 years, the topics of action observation (AO) and motor imagery
      (MI) have been largely studied in isolation from each other, despite the early
      integrative account by Jeannerod (1994, 2001). Recent neuroimaging studies
      demonstrate enhanced cortical activity when AO and MI are performed concurrently
      ("AO+MI"), compared to either AO or MI performed in isolation. These results
      indicate the potentially beneficial effects of AO+MI, and they also demonstrate
      that the underlying neurocognitive processes are partly shared. We separately
      review the evidence for MI and AO as forms of motor simulation, and present two
      quantitative literature analyses that indeed indicate rather little overlap
      between the two bodies of research. We then propose a spectrum of concurrent
      AO+MI states, from congruent AO+MI where the contents of AO and MI widely
      overlap, over coordinative AO+MI, where observed and imagined action are
      different but can be coordinated with each other, to cases of conflicting AO+MI.
      We believe that an integrative account of AO and MI is theoretically attractive,
      that it should generate novel experimental approaches, and that it can also
      stimulate a wide range of applications in sport, occupational therapy, and
      neurorehabilitation. 

PMID- 24324430
TI  - Estimating neuronal connectivity from axonal and dendritic density fields.
AB  - Neurons innervate space by extending axonal and dendritic arborizations. When
      axons and dendrites come in close proximity of each other, synapses between
      neurons can be formed. Neurons vary greatly in their morphologies and synaptic
      connections with other neurons. The size and shape of the arborizations determine
      the way neurons innervate space. A neuron may therefore be characterized by the
      spatial distribution of its axonal and dendritic "mass." A population mean "mass"
      density field of a particular neuron type can be obtained by averaging over the
      individual variations in neuron geometries. Connectivity in terms of candidate
      synaptic contacts between neurons can be determined directly on the basis of
      their arborizations but also indirectly on the basis of their density fields. To
      decide when a candidate synapse can be formed, we previously developed a
      criterion defining that axonal and dendritic line pieces should cross in 3D and
      have an orthogonal distance less than a threshold value. In this paper, we
      developed new methodology for applying this criterion to density fields. We show
      that estimates of the number of contacts between neuron pairs calculated from
      their density fields are fully consistent with the number of contacts calculated
      from the actual arborizations. However, the estimation of the connection
      probability and the expected number of contacts per connection cannot be
      calculated directly from density fields, because density fields do not carry
      anymore the correlative structure in the spatial distribution of synaptic
      contacts. Alternatively, these two connectivity measures can be estimated from
      the expected number of contacts by using empirical mapping functions. The neurons
      used for the validation studies were generated by our neuron simulator NETMORPH.
      An example is given of the estimation of average connectivity and Euclidean pre-
      and postsynaptic distance distributions in a network of neurons represented by
      their population mean density fields. 

PMID- 24324431
TI  - A permutation testing framework to compare groups of brain networks.
AB  - Brain network analyses have moved to the forefront of neuroimaging research over
      the last decade. However, methods for statistically comparing groups of networks
      have lagged behind. These comparisons have great appeal for researchers
      interested in gaining further insight into complex brain function and how it
      changes across different mental states and disease conditions. Current comparison
      approaches generally either rely on a summary metric or on mass-univariate nodal
      or edge-based comparisons that ignore the inherent topological properties of the
      network, yielding little power and failing to make network level comparisons.
      Gleaning deeper insights into normal and abnormal changes in complex brain
      function demands methods that take advantage of the wealth of data present in an
      entire brain network. Here we propose a permutation testing framework that allows
      comparing groups of networks while incorporating topological features inherent in
      each individual network. We validate our approach using simulated data with known
      group differences. We then apply the method to functional brain networks derived
      from fMRI data. 

PMID- 24324432
TI  - A hardware model of the auditory periphery to transduce acoustic signals into
      neural activity.
AB  - To improve the performance of cochlear implants, we have integrated a microdevice
      into a model of the auditory periphery with the goal of creating a
      microprocessor. We constructed an artificial peripheral auditory system using a
      hybrid model in which polyvinylidene difluoride was used as a piezoelectric
      sensor to convert mechanical stimuli into electric signals. To produce frequency
      selectivity, the slit on a stainless steel base plate was designed such that the
      local resonance frequency of the membrane over the slit reflected the transfer
      function. In the acoustic sensor, electric signals were generated based on the
      piezoelectric effect from local stress in the membrane. The electrodes on the
      resonating plate produced relatively large electric output signals. The signals
      were fed into a computer model that mimicked some functions of inner hair cells,
      inner hair cell-auditory nerve synapses, and auditory nerve fibers. In general,
      the responses of the model to pure-tone burst and complex stimuli accurately
      represented the discharge rates of high-spontaneous-rate auditory nerve fibers
      across a range of frequencies greater than 1 kHz and middle to high sound
      pressure levels. Thus, the model provides a tool to understand information
      processing in the peripheral auditory system and a basic design for connecting
      artificial acoustic sensors to the peripheral auditory nervous system. Finally,
      we discuss the need for stimulus control with an appropriate model of the
      auditory periphery based on auditory brainstem responses that were electrically
      evoked by different temporal pulse patterns with the same pulse number. 

PMID- 24324433
TI  - Sex dimorphism of cortical water diffusion in normal aging measured by magnetic
      resonance imaging.
AB  - BACKGROUND: The purpose of this study was to examine sex dimorphism in water
      diffusion in the brain throughout the normal aging process by magnetic resonance
      imaging. METHODS: Diffusion-weighted images covering the majority of the brain
      were acquired from 77 healthy participants. Both the mean water diffusivity and
      diffusion kurtosis were calculated from the cortical regions and parcellated
      according to the template in anatomical automatic labeling. The mean water
      diffusivity and diffusion kurtosis from both sexes were examined and subsequently
      correlated with age. Statistical significance was set at a threshold of p < 0.01
      after correction for multiple comparisons. In regions that reached statistical
      significance, a linear regression model was performed. Analysis of variance was
      conducted to determine the interaction between aging and sex. RESULTS: Sex
      differences were observed for three aspects. First, compared to females, males
      presented increased mean water diffusivity and a decreased diffusion kurtosis in
      the frontal and temporal lobes. Second, a widespread age-related increase in mean
      water diffusivity was observed, which was more significant in the frontal,
      occipital, and temporal areas and in the cingulum in females. Third, the
      diffusion kurtosis decreased with aging but only in restricted areas for both
      sexes. For the interaction of aging and sex, the most significant change was
      observed with regards to mean diffusivity, mostly in the right amygdala.
      CONCLUSIONS: A sex-related dimorphism in water diffusion throughout the aging
      process was observed in the cortex using magnetic resonance imaging.

PMID- 24324434
TI  - Tracking the Cognitive, Social, and Neuroanatomical Profile in Early
      Neurodegeneration: Type III Cockayne Syndrome.
AB  - Cockayne syndrome (CS) is an autosomal recessive disease associated with
      premature aging, progressive multiorgan degeneration, and nervous system
      abnormalities including cerebral and cerebellar atrophy, brain calcifications,
      and white matter abnormalities. Although several clinical descriptions of CS
      patients have reported developmental delay and cognitive impairment with relative
      preservation of social skills, no previous studies have carried out a
      comprehensive neuropsychological and social cognition assessment. Furthermore, no
      previous research in individuals with CS has examined the relationship between
      brain atrophy and performance on neuropsychological and social cognition tests.
      This study describes the case of an atypical late-onset type III CS patient who
      exceeds the mean life expectancy of individuals with this pathology. The patient
      and a group of healthy controls underwent a comprehensive assessment that
      included multiple neuropsychological and social cognition (emotion recognition,
      theory of mind, and empathy) tasks. In addition, we compared the pattern of
      atrophy in the patient to controls and to its concordance with ERCC8 gene
      expression in a healthy brain. The results showed memory, language, and executive
      deficits that contrast with the relative preservation of social cognition skills.
      The cognitive profile of the patient was consistent with his pattern of global
      cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral
      cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal
      regions), which in turn was anatomically consistent with the ERCC8 gene
      expression level in a healthy donor's brain. The study of exceptional cases, such
      as the one described here, is fundamental to elucidating the processes that
      affect the brain in premature aging diseases, and such studies provide an
      important source of information for understanding the problems associated with
      normal and pathological aging. 

PMID- 24324436
TI  - The discovery of rivaroxaban: translating preclinical assessments into clinical
      practice.
AB  - Direct oral anticoagulants that target a single coagulation factor (such as
      factor Xa or thrombin) have been developed in recent years in an attempt to
      address some of the limitations of traditional anticoagulants. Rivaroxaban is an
      oral, direct factor Xa inhibitor that inhibits free and clot-bound factor Xa and
      factor Xa in the prothrombinase complex. Preclinical studies demonstrated a
      potent anticoagulant effect of rivaroxaban in plasma as well as the ability of
      this agent to prevent and treat venous and arterial thrombosis in animal models.
      These studies led to an extensive phase I clinical development program that
      investigated the pharmacological properties of rivaroxaban in humans. In these
      studies, rivaroxaban was shown to exhibit predictable pharmacokinetics and
      pharmacodynamics and to have no clinically relevant interactions with many
      commonly prescribed co-medications. The pharmacodynamic effects of rivaroxaban
      (for example, inhibition of factor Xa and prolongation of prothrombin time) were
      closely correlated with rivaroxaban concentrations in plasma. The encouraging
      findings from preclinical and early clinical studies were expanded upon in large,
      randomized phase III studies, which demonstrated the clinical efficacy and safety
      of rivaroxaban in a broad spectrum of patients. This article provides an overview
      of the discovery and development of rivaroxaban, describing the pharmacodynamic
      profile established in preclinical studies and the optimal translation to
      clinical studies in healthy subjects and patient populations. 

PMID- 24324435
TI  - Neuroinflammation and brain functional disconnection in Alzheimer's disease.
AB  - Neuroinflammation and brain functional disconnection result from beta-amyloid
      (Abeta) accumulation and play fundamental roles in the pathogenesis of
      Alzheimer's disease (AD). We investigated possible correlations between these two
      AD-associated phenomena using DTI-based tractography and immunologic analyses in
      people with amnestic mild cognitive impairment (aMCI) and AD. DTI-Analyses
      focused on corpus callosum (CC). We found that frontal CC regions were preserved
      with respect to the posterior ones in aMCI; in these individuals significant
      correlations were seen between DTI-derived metrics in frontal-parietal CC areas
      and Abeta42-stimulated BDNF-producing CD4+ T lymphocytes and PDL-1-expressing
      CD14+ cells. These associations were lost in AD where DTI data involving the same
      CC areas correlated instead with Abeta42-stimulated interleukin (IL)-21 producing
      CD4+ T lymphocytes. Higher susceptibility to PDL-1-mediated apoptosis of Abeta42
      specific lymphocytes and BDNF-associated survival of existing neurons could
      contribute to the relative CC structure preservation seen in aMCI. These
      potentially protective mechanisms are lost in frank AD, when severe alterations
      in the CC are mirrored in peripheral blood by proinflammatory cytokines-producing
      T cells. Monitoring of immune cells in peripheral blood could have a prognostic
      value in AD. 

PMID- 24324437
TI  - Current clinical evidence on pioglitazone pharmacogenomics.
AB  - Pioglitazone is the most widely used thiazolidinedione and acts as an insulin
      sensitizer through activation of the Peroxisome Proliferator-Activated Receptor
      gamma (PPARgamma). Pioglitazone is approved for use in the management of type 2
      diabetes mellitus (T2DM), but its use in other therapeutic areas is increasing
      due to pleiotropic effects. In this hypothesis article, the current clinical
      evidence on pioglitazone pharmacogenomics is summarized and related to
      variability in pioglitazone response. How genetic variation in the human genome
      affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined.
      For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks
      of fracture or edema, and the increase in body mass index in response to
      pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the
      most extensively studied to date and selected polymorphisms contribute to
      respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We
      hypothesized that genetic variation in pioglitazone pathway genes contributes
      meaningfully to the clinically observed variability in drug response. To test the
      hypothesis that genetic variation in PPARG associates with variability in
      pioglitazone response, we conducted a meta-analysis to synthesize the currently
      available data on the PPARG p.Pro12Ala polymorphism. The results showed that
      PPARG 12Ala carriers had a more favorable change in fasting blood glucose from
      baseline as compared to patients with the wild-type Pro12Pro genotype (p =
      0.018). Unfortunately, findings for many other genes lack replication in
      independent cohorts to confirm association; further studies are needed. Also, the
      biological functionality of these polymorphisms is unknown. Based on current
      evidence, we propose that pharmacogenomics may provide an important tool to
      individualize pioglitazone therapy and better optimize therapy in patients with
      T2DM or other conditions for which pioglitazone is being used. 

PMID- 24324438
TI  - Increased sarcolemmal Na(+)/H(+) exchange activity in hypertrophied myocytes from
      dogs with chronic atrioventricular block.
AB  - Dogs with compensated biventricular hypertrophy due to chronic atrioventricular
      block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes
      arrhythmias and sudden cardiac death. It has been suggested that the increased
      Na(+) influx in hypertrophied cAVB ventricular myocytes contribute to these
      lethal arrhythmias. The increased Na(+) influx was not mediated by Na(+)
      channels, in fact the Na(+) current proved reduced in cAVB myocytes. Here we
      tested the hypothesis that increased activity of the Na(+)/H(+) exchanger type 1
      (NHE-1), commonly observed in hypertrophic hearts, causes the elevated Na(+)
      influx. Cardiac acid-base transport was studied with a pH-sensitive fluorescent
      dye in ventricular myocytes isolated from control and hypertrophied cAVB hearts;
      the H(+) equivalent flux through NHE-1, Na(+)-HCO(-) 3 cotransport (NBC), Cl(
      )/OH(-) exchange (CHE), and Cl(-)/HCO(-) 3 exchange (AE) were determined and
      normalized per liter cell water and corrected for surface-to-volume ratio. In
      cAVB, sarcolemmal NHE-1 flux was increased by 65 +/- 6.3% in the pH i interval
      6.3-7.2 and NBC, AE, and CHE fluxes remained unchanged. Accordingly, at steady
      state intracellular pH the total sarcolemmal Na(+) influx by NHE-1 + NBC
      increased from 8.5 +/- 1.5 amol/MUm(2)/min in normal myocytes to 15 +/- 2.4
      amol/MUm(2)/min in hypertrophied cAVB myocytes. We conclude that compensated
      cardiac hypertrophy in cAVB dogs is accompanied with an increased sarcolemmal NHE
      1 activity. This in conjunction with unchanged activity of the other acid-base
      transporters will raise the intracellular Na(+) in hypertrophied cAVB myocytes. 

PMID- 24324440
TI  - Sudden arrhythmic death: from basic science to clinical practice.

PMID- 24324439
TI  - Sphingosine 1-phosphate axis: a new leader actor in skeletal muscle biology.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive lipid involved in the regulation of
      biological processes such as proliferation, differentiation, motility, and
      survival. Here we review the role of S1P in the biology and homeostasis of
      skeletal muscle. S1P derives from the catabolism of sphingomyelin and is produced
      by sphingosine phosphorylation catalyzed by sphingosine kinase (SK). S1P can act
      either intracellularly or extracellularly through specific ligation to its five G
      protein-coupled receptors (GPCR) named S1P receptors (S1PR). Many experimental
      findings obtained in the last 20 years demonstrate that S1P and its metabolism
      play a multifaceted role in the regulation of skeletal muscle regeneration.
      Indeed, this lipid is known to activate muscle-resident satellite cells,
      regulating their proliferation and differentiation, as well as mesenchymal
      progenitors such as mesoangioblasts that originate outside skeletal muscle, both
      involved in tissue repair following an injury or disease. The molecular mechanism
      of action of S1P in skeletal muscle cell precursors is highly complex, especially
      because S1P axis is under the control of a number of growth factors and
      cytokines, canonical regulators of skeletal muscle biology. Moreover, this lipid
      is crucially involved in the regulation of skeletal muscle contractile
      properties, responsiveness to insulin, fatigue resistance and tropism. Overall,
      on the basis of these findings S1P signaling appears to be an appealing
      pharmacological target for improving skeletal muscle repair. Nevertheless,
      further understanding is required on the regulation of S1P downstream signaling
      pathways and the expression of S1PR. This article will resume our current
      knowledge on S1P signaling in skeletal muscle, hopefully stimulating further
      investigation in the field, aimed at individuating novel molecular targets for
      ameliorating skeletal muscle regeneration and reducing fibrosis of the tissue
      after a trauma or due to skeletal muscle diseases. 

PMID- 24324441
TI  - Central gene expression changes associated with enhanced neuroendocrine and
      autonomic response habituation to repeated noise stress after voluntary wheel
      running in rats.
AB  - Accumulating evidence indicates that regular physical exercise benefits health in
      part by counteracting some of the negative physiological impacts of stress. While
      some studies identified reductions in some measures of acute stress responses
      with prior exercise, limited data were available concerning effects on
      cardiovascular function, and reported effects on hypothalamic-pituitary
      adrenocortical (HPA) axis responses were largely inconsistent. Given that
      exposure to repeated or prolonged stress is strongly implicated in the
      precipitation and exacerbation of illness, we proposed the novel hypothesis that
      physical exercise might facilitate adaptation to repeated stress, and
      subsequently demonstrated significant enhancement of both HPA axis
      (glucocorticoid) and cardiovascular (tachycardia) response habituation to
      repeated noise stress in rats with long-term access to running wheels compared to
      sedentary controls. Stress habituation has been attributed to modifications of
      brain circuits, but the specific sites of adaptation and the molecular changes
      driving its expression remain unclear. Here, in situ hybridization histochemistry
      was used to examine regulation of select stress-associated signaling systems in
      brain regions representing likely candidates to underlie exercise-enhanced stress
      habituation. Analyzed brains were collected from active (6 weeks of wheel
      running) and sedentary rats following control, acute, or repeated noise exposures
      that induced a significantly faster rate of glucocorticoid response habituation
      in active animals but preserved acute noise responsiveness. Nearly identical
      experimental manipulations also induce a faster rate of cardiovascular response
      habituation in exercised, repeatedly stressed rats. The observed regulation of
      the corticotropin-releasing factor and brain-derived neurotrophic factor systems
      across several brain regions suggests widespread effects of voluntary exercise on
      central functions and related adaptations to stress across multiple response
      modalities. 

PMID- 24324442
TI  - Behavioral flexibility of the trawling long-legged bat, Macrophyllum macrophyllum
      (Phyllostomidae).
AB  - We assessed the behavioral flexibility of the trawling long-legged bat,
      Macrophyllum macrophyllum (Phyllostomidae) in flight cage experiments by exposing
      it to prey suspended from nylon threads in the air and to food placed onto the
      water surface at varying distances to clutter-producing background (water
      plants). The bat revealed flexibility in foraging mode and caught prey in the air
      (aerial hawking) and from the water surface (trawling). M. macrophyllum was
      constrained in finding food very near to and within clutter. As echolocation was
      the prime sensory mode used by M. macrophyllum for detection and localization of
      food, the bat might have been unable to perceive sufficient information from prey
      near clutter as background echoes from the water plant increasingly overlapped
      with echoes from food. The importance of echolocation for foraging is reflected
      in a stereotypic call pattern of M. macrophyllum that resembles other aerial
      insectivorous and trawling bats with a pronounced terminal phase (buzz) prior to
      capture attempts. Our findings contrast studies of other phyllostomid bats that
      glean prey very near or from vegetation, often using additional sensory cues,
      such as prey-produced noise, to find food and that lack a terminal phase in
      echolocation behavior. In M. macrophyllum, acoustic characteristics of its
      foraging habitat have shaped its sonar system more than phylogeny. 

PMID- 24324443
TI  - pH sensing via bicarbonate-regulated "soluble" adenylyl cyclase (sAC).
AB  - Soluble adenylyl cyclase (sAC) is a source of the second messenger cyclic
      adenosine 3', 5' monophosphate (cAMP). sAC is directly regulated by bicarbonate
      (HCO(-) 3) ions. In living cells, HCO(-) 3 ions are in nearly instantaneous
      equilibrium with carbon dioxide (CO2) and pH due to the ubiquitous presence of
      carbonic anhydrases. Numerous biological processes are regulated by CO2, HCO(-)
      3, and/or pH, and in a number of these, sAC has been shown to function as a
      physiological CO2/HCO3/pH sensor. In this review, we detail the known pH sensing
      functions of sAC, and we discuss two highly-studied, pH-dependent pathways in
      which sAC might play a role. 

PMID- 24324444
TI  - Relationship between Glutamate Dysfunction and Symptoms and Cognitive Function in
      Psychosis.
AB  - The glutamate hypothesis of schizophrenia, proposed over two decades ago,
      originated following the observation that administration of drugs that block NMDA
      glutamate receptors, such as ketamine, could induce schizophrenia-like symptoms.
      Since then, this hypothesis has been extended to describe how glutamate
      abnormalities may disturb brain function and underpin psychotic symptoms and
      cognitive impairments. The glutamatergic system is now a major focus for the
      development of new compounds in schizophrenia. Relationships between regional
      brain glutamate function and symptom severity can be investigated using proton
      magnetic resonance spectroscopy (1H-MRS) to estimate levels of glutamatergic
      metabolites in vivo. Here we briefly review the 1H-MRS studies that have explored
      relationships between glutamatergic metabolites, symptoms, and cognitive function
      in clinical samples. While some of these studies suggest that more severe
      symptoms may be associated with elevated glutamatergic function in the anterior
      cingulate, studies in larger patient samples selected on the basis of symptom
      severity are required. 

PMID- 24324446
TI  - The Puzzling Unidimensionality of DSM-5 Substance Use Disorder Diagnoses.
AB  - There is a perennial expert debate about the criteria to be included or excluded
      for the DSM diagnoses of substance use dependence. Yet analysts routinely report
      evidence for the unidimensionality of the resulting checklist. If in fact the
      checklist is unidimensional, the experts are wrong that the criteria are
      distinct, so either the experts are mistaken or the reported unidimensionality is
      spurious. I argue for the latter position, and suggest that the traditional
      reflexive measurement model is inappropriate for the DSM; a formative measurement
      model would be a more accurate characterization of the institutional process by
      which the checklist is created, and a network or causal model would be a more
      appropriate foundation for a scientifically grounded diagnostic system. 

PMID- 24324447
TI  - The Puzzling Unidimensionality of the DSM Substance Use Disorders: Commentary.

PMID- 24324445
TI  - A preliminary study of white matter in adolescent depression: relationships with
      illness severity, anhedonia, and irritability.
AB  - Major depressive disorder (MDD) during adolescence is a common and disabling
      psychiatric condition; yet, little is known about its neurobiological
      underpinning. Evidence indicates that MDD in adults involves alterations in white
      and gray matter; however, sparse research has focused on adolescent MDD.
      Similarly, little research has accounted for the wide variability of symptom
      severity among depressed teens. Here, we aimed to investigate white matter (WM)
      microstructure between 17 adolescents with MDD and 16 matched healthy controls
      (HC) using diffusion tensor imaging. We further assessed within the MDD group
      relationships between WM integrity and depression severity, as well as anhedonia
      and irritability - two core symptoms of adolescent MDD. As expected, adolescents
      with MDD manifested decreased WM integrity compared to HC in the anterior
      cingulum and anterior corona radiata. Within the MDD group, greater depression
      severity was correlated with reduced WM integrity in the genu of corpus callosum,
      anterior thalamic radiation, anterior cingulum, and sagittal stratum. However,
      anhedonia and irritability were associated with alterations in distinct WM
      tracts. Specifically, anhedonia was associated with disturbances in tracts
      related to reward processing, including the anterior limb of the internal capsule
      and projection fibers to the orbitofrontal cortex. Irritability was associated
      with decreased integrity in the sagittal stratum, anterior corona radiata, and
      tracts leading to prefrontal and temporal cortices. Overall, these preliminary
      findings provide further support for the hypotheses that there is a disconnect
      between prefrontal and limbic emotional regions in depression, and that specific
      clinical symptoms involve distinct alterations in WM tracts. 

PMID- 24324448
TI  - Confidence-based progress-driven self-generated goals for skill acquisition in
      developmental robots.
AB  - A reinforcement learning agent that autonomously explores its environment can
      utilize a curiosity drive to enable continual learning of skills, in the absence
      of any external rewards. We formulate curiosity-driven exploration, and eventual
      skill acquisition, as a selective sampling problem. Each environment setting
      provides the agent with a stream of instances. An instance is a sensory
      observation that, when queried, causes an outcome that the agent is trying to
      predict. After an instance is observed, a query condition, derived herein, tells
      whether its outcome is statistically known or unknown to the agent, based on the
      confidence interval of an online linear classifier. Upon encountering the first
      unknown instance, the agent "queries" the environment to observe the outcome,
      which is expected to improve its confidence in the corresponding predictor. If
      the environment is in a setting where all instances are known, the agent
      generates a plan of actions to reach a new setting, where an unknown instance is
      likely to be encountered. The desired setting is a self-generated goal, and the
      plan of action, essentially a program to solve a problem, is a skill. The success
      of the plan depends on the quality of the agent's predictors, which are improved
      as mentioned above. For validation, this method is applied to both a simulated
      and real Katana robot arm in its "blocks-world" environment. Results show that
      the proposed method generates sample-efficient curious exploration behavior,
      which exhibits developmental stages, continual learning, and skill acquisition,
      in an intrinsically-motivated playful agent. 

PMID- 24324449
TI  - Calculating and reporting effect sizes to facilitate cumulative science: a
      practical primer for t-tests and ANOVAs.
AB  - Effect sizes are the most important outcome of empirical studies. Most articles
      on effect sizes highlight their importance to communicate the practical
      significance of results. For scientists themselves, effect sizes are most useful
      because they facilitate cumulative science. Effect sizes can be used to determine
      the sample size for follow-up studies, or examining effects across studies. This
      article aims to provide a practical primer on how to calculate and report effect
      sizes for t-tests and ANOVA's such that effect sizes can be used in a-priori
      power analyses and meta-analyses. Whereas many articles about effect sizes focus
      on between-subjects designs and address within-subjects designs only briefly, I
      provide a detailed overview of the similarities and differences between within-
      and between-subjects designs. I suggest that some research questions in
      experimental psychology examine inherently intra-individual effects, which makes
      effect sizes that incorporate the correlation between measures the best summary
      of the results. Finally, a supplementary spreadsheet is provided to make it as
      easy as possible for researchers to incorporate effect size calculations into
      their workflow. 

PMID- 24324450
TI  - Beyond modeling abstractions: learning nouns over developmental time in atypical
      populations and individuals.
AB  - Connectionist models that capture developmental change over time have much to
      offer in the field of language development research. Several models in the
      literature have made good contact with developmental data, effectively captured
      behavioral tasks, and accurately represented linguistic input available to young
      children. However, fewer models of language development have truly captured the
      process of developmental change over time. In this review paper, we discuss
      several prominent connectionist models of early word learning, focusing on
      semantic development, as well as our recent work modeling the emergence of word
      learning biases in different populations. We also discuss the potential of these
      kinds of models to capture children's language development at the individual
      level. We argue that a modeling approach that truly captures change over time has
      the potential to inform theory, guide research, and lead to innovations in early
      language intervention. 

PMID- 24324451
TI  - Stop signals decrease choices for palatable foods through decreased food
      evaluation.
AB  - The present study explores whether presenting specific palatable foods in close
      temporal proximity of stop signals in a go/no-go task decreases subsequent
      evaluations of such foods among participants with a relatively high appetite.
      Furthermore, we tested whether any decreased evaluations could mediate subsequent
      food choice. Participants first received a go/no-go task in which palatable foods
      were consistently linked to go cues or no-go cues within participants. Next,
      evaluation of the palatable foods was measured as well as food choice.
      Replicating previous work, results show that among participants with a relatively
      high appetite palatable foods associated with no-go cues are less often chosen as
      snacks compared to when these foods are associated with go cues, whereas this
      manipulation did not affect participants with a relatively low appetite.
      Moreover, this effect was completely mediated by decreased evaluation of the
      palatable foods that had been associated with the no-go cues, whereas evaluation
      of the foods associated with go cues did not mediate this effect. Results further
      showed that the devaluation effect of foods associated with no-go cues was
      independent of the amount of pairings (4 vs. 12 vs. 24) with the no-go cues. The
      current findings suggest that decreased food evaluation is a mechanism that
      explains effects of stop signals on food choice. 

PMID- 24324452
TI  - Effect of prenatal cocaine on early postnatal thermoregulation and ultrasonic
      vocalization production.
AB  - Prenatal cocaine exposure can alter the postnatal care received by rat pups. Such
      effects could be caused in part by alterations in pup-produced stimuli that
      elicit early postnatal maternal care. Pup ultrasonic vocalizations are thought to
      be a particularly salient stimulus, and when paired with other cues, may elicit
      maternal attention. Cocaine is known to acutely alter thermoregulatory and
      cardiac function, thus prenatal cocaine may affect vocalizations through altering
      these functions. The data presented here determine the impact of full term
      prenatal cocaine exposure, saline exposure, or no exposure on thermogenic
      capacity, cardiac function, and the resulting ultrasonic vocalizations across the
      early postnatal period (days 1-5). Results indicated that while sharing many
      similar characteristics with saline-exposed and untreated animals, prenatal
      cocaine exposure was associated with specific alterations in vocalization
      characteristics on postnatal day 1 (PND 1), including call amplitude.
      Furthermore, numerous spectral parameters of their vocalizations were found
      altered on PND 3, including rate, call duration, and frequency, while no
      alterations were found on PND 5. Additionally, cocaine-exposed pups also showed a
      reduced thermoregulatory capacity compared to saline animals and reduced cardiac
      mass compared to untreated animals on PND 5. Together, these findings indicate
      that prenatal cocaine may be altering the elicitation of maternal care through
      its impact on vocalizations and thermoregulation, and suggests a potential
      mechanism for these effects through cocaine's impact on developing stress
      systems. 

PMID- 24324453
TI  - Visual attention for a desktop virtual environment with ambient scent.
AB  - In the current study participants explored a desktop virtual environment (VE)
      representing a suburban neighborhood with signs of public disorder (neglect,
      vandalism, and crime), while being exposed to either room air (control group), or
      subliminal levels of tar (unpleasant; typically associated with burned or waste
      material) or freshly cut grass (pleasant; typically associated with natural or
      fresh material) ambient odor. They reported all signs of disorder they noticed
      during their walk together with their associated emotional response. Based on
      recent evidence that odors reflexively direct visual attention to (either
      semantically or affectively) congruent visual objects, we hypothesized that
      participants would notice more signs of disorder in the presence of ambient tar
      odor (since this odor may bias attention to unpleasant and negative features),
      and less signs of disorder in the presence of ambient grass odor (since this odor
      may bias visual attention toward the vegetation in the environment and away from
      the signs of disorder). Contrary to our expectations the results provide no
      indication that the presence of an ambient odor affected the participants' visual
      attention for signs of disorder or their emotional response. However, the
      paradigm used in present study does not allow us to draw any conclusions in this
      respect. We conclude that a closer affective, semantic, or spatiotemporal link
      between the contents of a desktop VE and ambient scents may be required to
      effectively establish diagnostic associations that guide a user's attention. In
      the absence of these direct links, ambient scent may be more diagnostic for the
      physical environment of the observer as a whole than for the particular items in
      that environment (or, in this case, items represented in the VE). 

PMID- 24324454
TI  - Noticing relevant problem features: activating prior knowledge affects problem
      solving by guiding encoding.
AB  - This study investigated whether activating elements of prior knowledge can
      influence how problem solvers encode and solve simple mathematical equivalence
      problems (e.g., 3 + 4 + 5 = 3 + __). Past work has shown that such problems are
      difficult for elementary school students (McNeil and Alibali, 2000). One possible
      reason is that children's experiences in math classes may encourage them to think
      about equations in ways that are ultimately detrimental. Specifically, children
      learn a set of patterns that are potentially problematic (McNeil and Alibali,
      2005a): the perceptual pattern that all equations follow an "operations = answer"
      format, the conceptual pattern that the equal sign means "calculate the total",
      and the procedural pattern that the correct way to solve an equation is to
      perform all of the given operations on all of the given numbers. Upon viewing an
      equivalence problem, knowledge of these patterns may be reactivated, leading to
      incorrect problem solving. We hypothesized that these patterns may negatively
      affect problem solving by influencing what people encode about a problem. To test
      this hypothesis in children would require strengthening their misconceptions, and
      this could be detrimental to their mathematical development. Therefore, we tested
      this hypothesis in undergraduate participants. Participants completed either
      control tasks or tasks that activated their knowledge of the three patterns, and
      were then asked to reconstruct and solve a set of equivalence problems.
      Participants in the knowledge activation condition encoded the problems less well
      than control participants. They also made more errors in solving the problems,
      and their errors resembled the errors children make when solving equivalence
      problems. Moreover, encoding performance mediated the effect of knowledge
      activation on equivalence problem solving. Thus, one way in which experience may
      affect equivalence problem solving is by influencing what students encode about
      the equations. 

PMID- 24324455
TI  - Diabetes and the metabolic syndrome: possibilities of a new breath test in a
      dolphin model.
AB  - Diabetes type-2 and the metabolic syndrome are prevalent in epidemic proportions
      and result in significant co-morbid disease. Limitations in understanding of
      dietary effects and cholesterol metabolism exist. Current methods to assess
      diabetes are essential, though many are invasive; for example, blood glucose and
      lipid monitoring require regular finger sticks and blood draws. A novel method to
      study these diseases may be non-invasive breath testing of exhaled compounds.
      Currently, acetone and lipid peroxidation products have been seen in small scale
      studies, though other compounds may be significant. As Atlantic bottlenose
      dolphins (Tursiops truncatus) have been proposed as a good model for human
      diabetes, applications of dietary manipulations and breath testing in this
      population may shed important light on how to design human clinical studies. In
      addition, ongoing studies indicate that breath testing in dolphins is feasible,
      humane, and yields relevant metabolites. By studying the metabolic and
      cholesterol responses of dolphins to dietary modifications, researchers may gain
      insight into human diabetes, improve the design of costly human clinical trials,
      and potentially discover biomarkers for non-invasive breath monitoring. 

PMID- 24324456
TI  - Methodological limitations in determining astrocytic gene expression.
AB  - Traditionally, astrocytic mRNA and protein expression are studied by in situ
      hybridization (ISH) and immunohistochemically. This led to the concept that
      astrocytes lack aralar, a component of the malate-aspartate-shuttle. At least
      similar aralar mRNA and protein expression in astrocytes and neurons isolated by
      fluorescence-assisted cell sorting (FACS) reversed this opinion. Demonstration of
      expression of other astrocytic genes may also be erroneous. Literature data based
      on morphological methods were therefore compared with mRNA expression in cells
      obtained by recently developed methods for determination of cell-specific gene
      expression. All Na,K-ATPase-alpha subunits were demonstrated by
      immunohistochemistry (IHC), but there are problems with the cotransporter NKCC1.
      Glutamate and GABA transporter gene expression was well determined
      immunohistochemically. The same applies to expression of many genes of glucose
      metabolism, whereas a single study based on findings in bacterial artificial
      chromosome (BAC) transgenic animals showed very low astrocytic expression of
      hexokinase. Gene expression of the equilibrative nucleoside transporters ENT1 and
      ENT2 was recognized by ISH, but ENT3 was not. The same applies to the
      concentrative transporters CNT2 and CNT3. All were clearly expressed in FACS
      isolated cells, followed by biochemical analysis. ENT3 was enriched in
      astrocytes. Expression of many nucleoside transporter genes were shown by
      microarray analysis, whereas other important genes were not. Results in cultured
      astrocytes resembled those obtained by FACS. These findings call for reappraisal
      of cellular nucleoside transporter expression. FACS cell yield is small. Further
      development of cell separation methods to render methods more easily available
      and less animal and cost consuming and parallel studies of astrocytic mRNA and
      protein expression by ISH/IHC and other methods are necessary, but new methods
      also need to be thoroughly checked. 

PMID- 24324457
TI  - Paracrine mechanisms involved in the control of early stages of Mammalian
      spermatogenesis.
AB  - Within the testis, Sertoli-cell is the primary target of pituitary FSH. Several
      growth factors have been described to be produced specifically by Sertoli cells
      and modulate male germ cell development through paracrine mechanisms. Some have
      been shown to act directly on spermatogonia such as GDNF, which acts on self
      renewal of spermatogonial stem cells (SSCs) while inhibiting their
      differentiation; BMP4, which has both a proliferative and differentiative effect
      on these cells, and KIT ligand (KL), which stimulates the KIT tyrosine-kinase
      receptor expressed by differentiating spermatogonia (but not by SSCs). KL not
      only controls the proliferative cycles of KIT-positive spermatogonia, but it also
      stimulates the expression of genes that are specific of the early phases of
      meiosis, whereas the expression of typical spermatogonial markers is down
      regulated. On the contrary, FGF9 acts as a meiotic inhibiting substance both in
      fetal gonocytes and in post-natal spermatogonia through the induction of the RNA
      binding protein NANOS2. Vitamin A, which is metabolized to Retinoic Acid in
      Sertoli cells, controls both SSCs differentiation through KIT induction and
      NANOS2 inhibition, and meiotic entry of differentiating spermatogonia through
      STRA8 upregulation. 

PMID- 24324458
TI  - Control of ventricular ciliary beating by the melanin concentrating hormone
      expressing neurons of the lateral hypothalamus: a functional imaging survey.
AB  - The cyclic peptide Melanin Concentrating Hormone (MCH) is known to control a
      large number of brain functions in mammals such as food intake and metabolism,
      stress response, anxiety, sleep/wake cycle, memory, and reward. Based on neuro
      anatomical and electrophysiological studies these functions were attributed to
      neuronal circuits expressing MCHR1, the single MCH receptor in rodents. In
      complement to our recently published work (1) we provided here new data regarding
      the action of MCH on ependymocytes in the mouse brain. First, we establish that
      MCHR1 mRNA is expressed in the ependymal cells of the third ventricle epithelium.
      Second, we demonstrated a tonic control of MCH-expressing neurons on ependymal
      cilia beat frequency using in vitro optogenics. Finally, we performed in vivo
      measurements of CSF flow using fluorescent micro-beads in wild-type and MCHR1
      knockout mice. Collectively, our results demonstrated that MCH-expressing neurons
      modulate ciliary beating of ependymal cells at the third ventricle and could
      contribute to maintain cerebro-spinal fluid homeostasis. 

PMID- 24324459
TI  - Thyroid Hormone Upregulates Hypothalamic kiss2 Gene in the Male Nile Tilapia,
      Oreochromis niloticus.
AB  - Kisspeptin has recently been recognized as a critical regulator of reproductive
      function in vertebrates. During the sexual development, kisspeptin neurons
      receive sex steroids feedback to trigger gonadotropin-releasing hormone (GnRH)
      neurons. In teleosts, a positive correlation has been found between the thyroid
      status and the reproductive status. However, the role of thyroid hormone in the
      regulation of kisspeptin system remains unknown. We cloned and characterized a
      gene encoding kisspeptin (kiss2) in a cichlid fish, the Nile tilapia (Oreochromis
      niloticus). Expression of kiss2 mRNA in the brain was analyzed by in situ
      hybridization. The effect of thyroid hormone (triiodothyronine, T3) and
      hypothyroidism with methimazole (MMI) on kiss2 and the three GnRH types (gnrh1,
      gnrh2, and gnrh3) mRNA expression was analyzed by real-time PCR. Expression of
      thyroid hormone receptor mRNAs were analyzed in laser-captured kisspeptin and
      GnRH neurons by RT-PCR. The kiss2 mRNA expressing cells were seen in the nucleus
      of the lateral recess in the hypothalamus. Intraperitoneal administration of T3
      (5 MUg/g body weight) to sexually mature male tilapia significantly increased
      kiss2 and gnrh1 mRNA levels at 24 h post injection (P < 0.001), while the
      treatment with an anti-thyroid, MMI (100 ppm for 6 days) significantly reduced
      kiss2 and gnrh1 mRNA levels (P < 0.05). gnrh2, gnrh3, and thyrotropin-releasing
      hormone mRNA levels were insensitive to the thyroid hormone manipulations.
      Furthermore, RT-PCR showed expression of thyroid hormone receptor mRNAs in laser
      captured GnRH neurons but not in kiss2 neurons. This study shows that GnRH1 may
      be directly regulated through thyroid hormone, while the regulation of Kiss2 by
      T3 is more likely to be indirect. 

PMID- 24324460
TI  - Metatranscriptomic and functional metagenomic analysis of methylphosphonate
      utilization by marine bacteria.
AB  - Aerobic degradation of methylphosphonate (MPn) by marine bacterioplankton has
      been hypothesized to contribute significantly to the ocean's methane
      supersaturation, yet little is known about MPn utilization by marine microbes. To
      identify the microbial taxa and metabolic functions associated with MPn-driven
      methane production we performed parallel metagenomic, metatranscriptomic, and
      functional screening of microcosm perturbation experiments using surface water
      collected in the North Pacific Subtropical Gyre. In nutrient amended microcosms
      containing MPn, a substrate-driven microbial succession occurred. Initially, the
      addition of glucose and nitrate resulted in a bloom of Vibrionales and a
      transcriptional profile dominated by glucose-specific PTS transport and
      polyhydroxyalkanoate biosynthesis. Transcripts associated with phosphorus (P)
      acquisition were also overrepresented and suggested that the addition of glucose
      and nitrate had driven the community to P depletion. At this point, a second
      community shift occurred characterized by the increase in C-P lyase containing
      microbes of the Vibrionales and Rhodobacterales orders. Transcripts associated
      with C-P lyase components were among the most highly expressed at the community
      level, and only C-P lyase clusters were recovered in a functional screen for MPn
      utilization, consistent with this pathway being responsible for the majority, if
      not all, of the methane accumulation we observed. Our results identify specific
      bacterioplankton taxa that can utilize MPn aerobically under conditions of P
      limitation using the C-P lyase pathway, and thereby elicit a significant increase
      in the dissolved methane concentration. 

PMID- 24324461
TI  - Phylogenetic significance of composition and crystal morphology of magnetosome
      minerals.
AB  - Magnetotactic bacteria (MTB) biomineralize magnetosomes, nano-scale crystals of
      magnetite or greigite in membrane enclosures that comprise a permanent magnetic
      dipole in each cell. MTB control the mineral composition, habit, size, and
      crystallographic orientation of the magnetosomes, as well as their arrangement
      within the cell. Studies involving magnetosomes that contain mineral and
      biological phases require multidisciplinary efforts. Here we use
      crystallographic, genomic and phylogenetic perspectives to review the
      correlations between magnetosome mineral habits and the phylogenetic affiliations
      of MTB, and show that these correlations have important implications for the
      evolution of magnetosome synthesis, and thus magnetotaxis. 

PMID- 24324462
TI  - Development of oligomannose-coated liposome-based nasal vaccine against human
      parainfluenza virus type 3.
AB  - Human parainfluenza viruses (HPIVs) are the etiologic agents of lower respiratory
      infections and pneumonia in infants, young children and immunocompromised hosts.
      The overarching goal for the prevention of HPIV infection is the development of
      an effective vaccine against HPIVs. In the present study, we investigated the
      effectiveness of oligomannose-coated liposomes (OMLs) as an antigen-delivery
      system in combination with a synthetic double-stranded RNA analog for the
      induction of mucosal and systematic immunity against HPIV3. Full-length
      hemagglutinin-neuraminidase (HN) protein was synthesized using the wheat germ
      cell-free protein production system and then encapsulated into OML to serve as
      the antigen. Intranasal administration of the HN-filling OML (OML-HN) with the
      synthetic double-stranded RNA adjuvant, polyriboinosinic-polyribocytidylic acid
      [poly(I:C)] generated significant viral-specific systemic and mucosal immune
      responses as evidenced by the prominent induction of serum IgG and nasal wash
      IgA, respectively. On the other hand, no significant immune responses were
      observed in mice immunized with OML-HN without the adjuvant. Furthermore, serum
      from mice immunized with OML-HN plus poly(I:C) significantly suppressed viral
      infection in cell culture model. Our results provide the first evidence that
      intranasal co-administration of OML-encapsulated HN with the poly(I:C) adjuvant
      augments the viral-specific immunity against HPIV3. 

PMID- 24324463
TI  - Sorbic acid stress activates the Candida glabrata high osmolarity glycerol MAP
      kinase pathway.
AB  - Weak organic acids such as sorbic acid are important food preservatives and
      powerful fungistatic agents. These compounds accumulate in the cytosol and
      disturb the cellular pH and energy homeostasis. Candida glabrata is in many
      aspects similar to Saccharomyces cerevisiae. However, with regard to
      confrontation to sorbic acid, two of the principal response pathways behave
      differently in C. glabrata. In yeast, sorbic acid stress causes activation of
      many genes via the transcription factors Msn2 and Msn4. The C. glabrata homologs
      CgMsn2 and CgMsn4 are apparently not activated by sorbic acid. In contrast, in C.
      glabrata the high osmolarity glycerol (HOG) pathway is activated by sorbic acid.
      Here we show that the MAP kinase of the HOG pathway, CgHog1, becomes
      phosphorylated and has a function for weak acid stress resistance. Transcript
      profiling of weak acid treated C. glabrata cells suggests a broad and very
      similar response pattern of cells lacking CgHog1 compared to wild type which is
      over lapping with but distinct from S. cerevisiae. The PDR12 gene was the highest
      induced gene in both species and it required CgHog1 for full expression. Our
      results support flexibility of the response cues for general stress signaling
      pathways, even between closely related yeasts, and functional extension of a
      specific response pathway. 

PMID- 24324464
TI  - The magnetosome model: insights into the mechanisms of bacterial
      biomineralization.
AB  - Though the most ready example of biomineralization is the calcium phosphate of
      vertebrate bones and teeth, many bacteria are capable of creating biominerals
      inside their cells. Because of the diversity of these organisms and the minerals
      they produce, their study may reveal aspects of the fundamental mechanisms of
      biomineralization in more complex organisms. The best-studied case of
      intracellular biomineralization in bacteria is the magnetosome, an organelle
      produced by a diverse group of aquatic bacteria that contains single-domain
      crystals of the iron oxide magnetite (Fe3O4) or the iron sulfide greigite
      (Fe3S4). Here, recent advances in our understanding of the mechanisms of
      bacterial magnetite biomineralization are discussed and used as a framework for
      understanding less-well studied examples, including the bacterial intracellular
      biomineralization of cadmium, selenium, silver, nickel, uranium, and calcium
      carbonate. Understanding the molecular mechanisms underlying the biological
      formation of these minerals will have important implications for technologies
      such as the fabrication of nanomaterials and the bioremediation of toxic
      compounds. 

PMID- 24324465
TI  - Maternal Supplementation with LGG Reduces Vaccine-Specific Immune Responses in
      Infants at High-Risk of Developing Allergic Disease.
AB  - Probiotics are defined as live micro-organisms that when administered in adequate
      amounts confer a health benefit on the host. Among their pleiotropic effects,
      inhibition of pathogen colonization at the mucosal surface as well as modulation
      of immune responses are widely recognized as the principal biological activities
      of probiotic bacteria. In recent times, the immune effects of probiotics have led
      to their application as vaccine adjuvants, offering a novel strategy for
      enhancing the efficacy of current vaccines. Such an approach is particularly
      relevant in regions where infectious disease burden is greatest and where access
      to complete vaccination programs is limited. In this study, we report the effects
      of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to
      tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7)
      vaccines in infants. This study was conducted as part of a larger clinical trial
      assessing the impact of maternal LGG supplementation in preventing the
      development of atopic eczema in infants at high-risk for developing allergic
      disease. Maternal LGG supplementation was associated with reduced antibody
      responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N =
      31) compared to placebo treatment (N = 30) but not total IgG levels. Maternal LGG
      supplementation was also associated with a trend to increased number of tetanus
      toxoid-specific T regulatory in the peripheral blood compared to placebo-treated
      infants. These findings suggest that maternal LGG supplementation may not be
      beneficial in terms of improving vaccine-specific immunity in infants. Further
      clinical studies are needed to confirm these findings. As probiotic immune
      effects can be species/strain specific, our findings do not exclude the potential
      use of other probiotic bacteria to modulate infant immune responses to vaccines. 

PMID- 24324466
TI  - MHC Class II Protein Turnover In vivo and Its Relevance for Autoimmunity in Non
      Obese Diabetic Mice.
AB  - Major histocompatibility complex class II (MHCII) proteins are loaded with
      endosomal peptides and reside at the surface of antigen-presenting cells (APCs)
      for a time before being degraded. In vitro, MHCII protein levels and turnover are
      affected by peptide loading and by rates of ubiquitin-dependent internalization
      from the cell surface, which is in turn affected by APC type and activation
      state. Prior work suggested that fast turnover of disease-associated MHCII
      alleles may contribute to autoimmunity. We recently developed novel stable
      isotope tracer techniques to test this hypothesis in vivo. In non-obese diabetic
      (NOD) mice, a model of type 1 diabetes (T1D), MHCII turnover was affected by APC
      type, but unaffected by disease-associated structural polymorphism. Differences
      in MHCII turnover were observed between NOD colonies with high and low T1D
      incidence, but fast turnover was dispensable for autoimmunity. Moreover, NOD mice
      with gene knockouts of peptide loading cofactors do not develop T1D. Thus, fast
      turnover does not appear pathogenic, and conventional antigen presentation is
      critical for autoimmunity in NOD mice. However, shared environmental factors may
      underpin colony differences in MHCII protein turnover, immune regulation, and
      pathogenesis. 

PMID- 24324467
TI  - Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14(+) Cells at the Cross
      Roads of Immune Activation and Suppression.
AB  - Tumors abuse myeloid plasticity to re-direct dendritic cell (DC) differentiation
      from T cell stimulatory subsets to immune-suppressive subsets that can interfere
      with anti-tumor immunity. Lined by a dense network of easily accessible DC the
      skin is a preferred site for the delivery of DC-targeted vaccines. Various groups
      have recently been focusing on functional aspects of DC subsets in the skin and
      how these may be affected by tumor-derived suppressive factors. IL-6,
      Prostaglandin-E2, and IL-10 were identified as factors in cultures of primary
      human tumors responsible for the inhibited development and activation of skin DC
      as well as monocyte-derived DC. IL-10 was found to be uniquely able to convert
      fully developed DC to immature macrophage-like cells with functional M2
      characteristics in a physiologically highly relevant skin explant model in which
      the phenotypic and functional traits of "crawl-out" DC were studied. Mostly from
      mouse studies, the JAK2/STAT3 signaling pathway has emerged as a "master switch"
      of tumor-induced immune suppression. Our lab has additionally identified p38-MAPK
      as an important signaling element in human DC suppression, and recently validated
      it as such in ex vivo cultures of single-cell suspensions from melanoma
      metastases. Through the identification of molecular mechanisms and signaling
      events that drive myeloid immune suppression in human tumors, more effective DC
      targeted cancer vaccines may be designed. 

PMID- 24324468
TI  - Human decidual NK cells: unique and tightly regulated effector functions in
      healthy and pathogen-infected pregnancies.
AB  - NK cells present in the peripheral blood (PB) respond rapidly to pathogens or
      pathogen-infected cells by various means including cytotoxicity and release of
      cytokines and chemokines. In addition they modulate adaptive immunity via the
      interaction with dendritic cells. Decidual NK cells (dNK) are poorly cytotoxic in
      healthy pregnancy, both in humans and rodents, when compared to their PB
      counterparts. We will discuss recent findings that may contribute to answer the
      following questions: (i) Do dNK possess functional killing machinery in normal
      healthy pregnancy? (ii) If so, what are the regulatory mechanisms that negatively
      control this effector function? (iii) Have dNK from early pregnant uterus the
      intrinsic ability to kill pathogen-infected autologous maternal uterine cells
      and/or produce soluble factors that stimulate the anti-pathogen adaptive immune
      response? (iv) Do dNK undergo a receptor repertoire profile shift when they are
      in contact with pathogen-infected uterine cells? (v) Which pathogen-mediated
      signal(s) and molecular interactions subvert the inhibition of dNK cytolytic
      activity? 

PMID- 24324469
TI  - Neuropilin-1 in transplantation tolerance.
AB  - In the immune system, Neuropilin-1 (Nrp1) is a molecule that plays an important
      role in establishing the immunological synapse between dendritic cells (DCs) and
      T cells. Recently, Nrp1 has been identified as a marker that seems to distinguish
      natural T regulatory (nTreg) cells, generated in the thymus, from inducible T
      regulatory (iTreg) cells raised in the periphery. Given the crucial role of both
      nTreg and iTreg cells in the generation and maintenance of immune tolerance, the
      ability to phenotypically identify each of these cell populations in vivo is
      needed to elucidate their biological properties. In turn, these properties have
      the potential to be developed for therapeutic use to promote immune tolerance.
      Here we describe the nature and functions of Nrp1, including its potential use as
      a therapeutic target in transplantation tolerance. 

PMID- 24324470
TI  - A critical analysis of rejection in vascularized composite allotransplantation:
      clinical, cellular and molecular aspects, current challenges, and novel concepts.
AB  - Advances in microsurgical techniques and immunomodulatory protocols have
      contributed to the expansion of vascularized composite allotransplantation (VCA)
      with very encouraging immunological, functional, and cosmetic results. Rejection
      remains however a major hurdle that portends serious threats to recipients.
      Rejection features in VCA have been described in a number of studies, and an
      international consensus on the classification of rejection was established.
      Unfortunately, current available diagnostic methods carry many shortcomings that,
      in certain cases, pose a great diagnostic challenge to physicians especially in
      borderline rejection cases. In this review, we revisit the features of acute skin
      rejection in hand and face transplantation at the clinical, cellular, and
      molecular levels. The multiple challenges in diagnosing rejection and in defining
      chronic and antibody-mediated rejection in VCA are then presented, and we finish
      by analyzing current research directions and novel concepts aiming at improving
      available diagnostic measures. 

PMID- 24324472
TI  - The proteoglycan glycomatrix: a sugar microenvironment essential for complement
      regulation.

PMID- 24324471
TI  - Tumor-primed NK cells: waiting for the green light.
AB  - The functional impairment of natural killer (NK) cells has been frequently
      reported in cancer studies. As one of the central components of host anti-tumor
      immunity, NK cells exert cellular cytotoxicity against tumor cells, and secrete a
      cytokine milieu to inhibit tumor progression and enable the recruitment of other
      immune cells to the tumor site. The unlocking of the full functional potential of
      NK cells requires successful progression through discrete activation stages that
      are tightly regulated by a complex array of signaling molecules. Target cell
      susceptibility to NK cell-mediated killing is dependent on the intensity and
      specific combination of ligand expression for NK cell receptors. Tumor cells
      utilize numerous strategies for evading NK cells, including the downregulation of
      important NK cell-activating ligands. Here, we review key studies on NK cell
      activation requirements, and argue, based on our findings from NK cell-tumor
      interactions, that the altered characteristics of tumor-associated NK cells are
      indicative of unmet signaling requirements for full NK cell activation, rather
      than NK cell dysfunction in cancer. 

PMID- 24324473
TI  - Bark flammability as a fire-response trait for subalpine trees.
AB  - Relationships between the flammability properties of a given plant and its
      chances of survival after a fire still remain unknown. We hypothesize that the
      bark flammability of a tree reduces the potential for tree survival following
      surface fires, and that if tree resistance to fire is provided by a thick
      insulating bark, the latter must be few flammable. We test, on subalpine tree
      species, the relationship between the flammability of bark and its insulating
      ability, identifies the biological traits that determine bark flammability, and
      assesses their relative susceptibility to surface fires from their bark
      properties. The experimental set of burning properties was analyzed by Principal
      Component Analysis to assess the bark flammability. Bark insulating ability was
      expressed by the critical time to cambium kill computed from bark thickness. Log
      linear regressions indicated that bark flammability varies with the bark
      thickness and the density of wood under bark and that the most flammable barks
      have poor insulating ability. Susceptibility to surface fires increases from
      gymnosperm to angiosperm subalpine trees. The co-dominant subalpine species Larix
      decidua (Mill.) and Pinus cembra (L.) exhibit large differences in both
      flammability and insulating ability of the bark that should partly explain their
      contrasted responses to fires in the past. 

PMID- 24324474
TI  - Physiological and growth responses to water deficit in the bioenergy crop
      Miscanthus x giganteus.
AB  - High yielding perennial biomass crops of the species Miscanthus are widely
      recognized as one of the most promising lignocellulosic feedstocks for the
      production of bioenergy and bioproducts. Miscanthus is a C4 grass and thus has
      relatively high water use efficiency. Cultivated Miscanthus comprises primarily
      of a single clone, Miscanthus x giganteus, a sterile hybrid between M.
      sacchariflorus and M. sinensis. M. x giganteus is high yielding and expresses
      desirable combinations of many traits present in the two parental species types;
      however, it responds poorly to low water availability. To identify the
      physiological basis of the response to water stress in M. x giganteus and to
      identify potential targets for breeding improvements we characterized the
      physiological responses to water-deficit stress in a pot experiment. The
      experiment has provided valuable insights into the temporal aspects of drought
      induced responses of M. x giganteus. Withholding water resulted in marked changes
      in plant physiology with growth-associated traits among the first affected, the
      most rapid response being a decline in the rate of stem elongation. A reduction
      in photosynthetic performance was among the second set of changes observed;
      indicated by a decrease in stomatal conductance followed by decreases in
      chlorophyll fluorescence and chlorophyll content. Measures reflecting the plant
      water status were among the last affected by the drought treatment. Metabolite
      analysis indicated that proline was a drought stress marker in M. x giganteus,
      metabolites in the proline synthesis pathway were more abundant when stomatal
      conductance decreased and dry weight accumulation ceased. The outcomes of this
      study in terms of drought-induced physiological changes, accompanied by a proof
      of-concept metabolomics investigation, provide a platform for identifying targets
      for improved drought-tolerance of the Miscanthus bioenergy crop. 

PMID- 24324476
TI  - Phloem: the integrative avenue for resource distribution, signaling, and defense.

PMID- 24324477
TI  - Studying the oxidation of water to molecular oxygen in photosynthetic and
      artificial systems by time-resolved membrane-inlet mass spectrometry.
AB  - Monitoring isotopic compositions of gaseous products (e.g., H2, O2, and CO2) by
      time-resolved isotope-ratio membrane-inlet mass spectrometry (TR-IR-MIMS) is
      widely used for kinetic and functional analyses in photosynthesis research. In
      particular, in combination with isotopic labeling, TR-MIMS became an essential
      and powerful research tool for the study of the mechanism of photosynthetic water
      oxidation to molecular oxygen catalyzed by the water-oxidizing complex of
      photosystem II. Moreover, recently, the TR-MIMS and (18)O-labeling approach was
      successfully applied for testing newly developed catalysts for artificial water
      splitting and provided important insight about the mechanism and pathways of O2
      formation. In this mini-review we summarize these results and provide a brief
      introduction into key aspects of the TR-MIMS technique and its perspectives for
      future studies of the enigmatic water-splitting chemistry. 

PMID- 24324479
TI  - Hypothesis: increase of the ratio singlet oxygen plus superoxide radical to
      hydrogen peroxide changes stress defense response to programmed leaf death.
AB  - The level of reactive oxygen species (ROS) increases under different stresses
      and, by destroying cellular components, may cause cell death. In addition, ROS
      are part of the complex network of transduction signals that induce defense
      reactions against stress or, alternatively, trigger programmed cell death, and
      key questions are the levels of each ROS that, respectively determine defense and
      death responses of the cell. The answer to those questions is difficult because
      there are several patterns of cell death that frequently appear mixed and are
      hardly distinguishable. Moreover, although considerable progresses have been
      achieved in the determination of the levels of specific ROS, critical questions
      remain on the ROS level in specific cell compartments. By considering
      chloroplasts as the main source of ROS in photosynthetic tissues at light, a
      comparison of the levels in stress and senescence of the chloroplastic activities
      involved in the generation and scavenging of ROS suggests plausible differences
      in the levels of specific ROS between stress defense and death. In effect, the
      three activities of the chlororespiratory chain increase similarly in stress
      defense response. However, in senescence, superoxide dismutase (SOD), that
      converts superoxide anion radical ([Formula: see text]) to hydrogen peroxide
      (H2O2,) decreases, while the thylakoid Ndh complex, that favors the generation of
      singlet oxygen ((1)O2) and [Formula: see text], and peroxidase (PX), that
      consumes H2O2, increase. The obvious inference is that, in respect to defense
      response, the ratio ((1)O2 plus [Formula: see text])/H2O2 is increased in the
      senescence previous to cell death. We hypothesize that the different ROS ratios,
      probably through changes in the jasmonic acid/H2O2 ratio, could determine the
      activation of the defense network or the death network response of the cell. 

PMID- 24324480
TI  - Unleashing the potential of the root hair cell as a single plant cell type model
      in root systems biology.
AB  - Plant root is an organ composed of multiple cell types with different functions.
      This multicellular complexity limits our understanding of root biology because 
      omics studies performed at the level of the entire root reflect the average
      responses of all cells composing the organ. To overcome this difficulty and allow
      a more comprehensive understanding of root cell biology, an approach is needed
      that would focus on one single cell type in the plant root. Because of its
      biological functions (i.e., uptake of water and various nutrients; primary site
      of infection by nitrogen-fixing bacteria in legumes), the root hair cell is an
      attractive single cell model to study root cell response to various stresses and
      treatments. To fully study their biology, we have recently optimized procedures
      in obtaining root hair cell samples. We culture the plants using an ultrasound
      aeroponic system maximizing root hair cell density on the entire root systems and
      allowing the homogeneous treatment of the root system. We then isolate the root
      hair cells in liquid nitrogen. Isolated root hair yields could be up to 800 to
      1000~mg of plant cells from 60 root systems. Using soybean as a model, the purity
      of the root hair was assessed by comparing the expression level of genes
      previously identified as soybean root hair specific between preparations of
      isolated root hair cells and stripped roots, roots devoid in root hairs.
      Enlarging our tests to include other plant species, our results support the
      isolation of large quantities of highly purified root hair cells which is
      compatible with a systems biology approach. 

PMID- 24324475
TI  - Redox regulation of the Calvin-Benson cycle: something old, something new.
AB  - Reversible redox post-translational modifications such as oxido-reduction of
      disulfide bonds, S-nitrosylation, and S-glutathionylation, play a prominent role
      in the regulation of cell metabolism and signaling in all organisms. These
      modifications are mainly controlled by members of the thioredoxin and
      glutaredoxin families. Early studies in photosynthetic organisms have identified
      the Calvin-Benson cycle, the photosynthetic pathway responsible for carbon
      assimilation, as a redox regulated process. Indeed, 4 out of 11 enzymes of the
      cycle were shown to have a low activity in the dark and to be activated in the
      light through thioredoxin-dependent reduction of regulatory disulfide bonds. The
      underlying molecular mechanisms were extensively studied at the biochemical and
      structural level. Unexpectedly, recent biochemical and proteomic studies have
      suggested that all enzymes of the cycle and several associated regulatory
      proteins may undergo redox regulation through multiple redox post-translational
      modifications including glutathionylation and nitrosylation. The aim of this
      review is to detail the well-established mechanisms of redox regulation of Calvin
      Benson cycle enzymes as well as the most recent reports indicating that this
      pathway is tightly controlled by multiple interconnected redox post-translational
      modifications. This redox control is likely allowing fine tuning of the Calvin
      Benson cycle required for adaptation to varying environmental conditions,
      especially during responses to biotic and abiotic stresses. 

PMID- 24324478
TI  - Missing links in understanding redox signaling via thiol/disulfide modulation:
      how is glutathione oxidized in plants?
AB  - Glutathione is a small redox-active molecule existing in two main stable forms:
      the thiol (GSH) and the disulphide (GSSG). In plants growing in optimal
      conditions, the GSH:GSSG ratio is high in most cell compartments. Challenging
      environmental conditions are known to alter this ratio, notably by inducing the
      accumulation of GSSG, an effect that may be influential in the perception or
      transduction of stress signals. Despite the potential importance of glutathione
      status in redox signaling, the reactions responsible for the oxidation of GSH to
      GSSG have not been clearly identified. Most attention has focused on the
      ascorbate-glutathione pathway, but several other candidate pathways may couple
      the availability of oxidants such as H2O2 to changes in glutathione and thus
      impact on signaling pathways through regulation of protein thiol-disulfide
      status. We provide an overview of the main candidate pathways and discuss the
      available biochemical, transcriptomic, and genetic evidence relating to each. Our
      analysis emphasizes how much is still to be elucidated on this question, which is
      likely important for a full understanding of how stress-related redox regulation
      might impinge on phytohormone-related and other signaling pathways in plants. 

PMID- 24324481
TI  - Students' perspective on genomics: from sample to sequence using the case study
      of blueberry.
AB  - Advances in genomic sequencing technologies in the past decade have
      revolutionized the field of genomics, resulting in faster and less expensive
      sequencing. Holding back the potential for innovation, however, is a widespread
      lack of understanding of genomics and sequencing by the general public. In an
      attempt to remedy this problem, this paper presents an introduction to the fields
      of genomics, bioinformatics, and proteomics using the blueberry genome as a model
      case study of the plant genomics field. The blueberry (Vaccinium sect.
      Cyanococcus) is often cited as a "super food" in the media due to its nutritional
      benefits and global economic importance. There have been a number of related
      genomic publications in the past 20 years; however, a completed genome and a full
      analysis into the health-related pathways are still needed. As exemplified by
      this blueberry case study, there are opportunities for future genomic research
      into numerous beneficial plant species. The solid background presented in this
      paper provides future researchers the foundation to explore these uncharted
      areas. 

PMID- 24324482
TI  - MicroRNA basis of physiological hypertrophy.

PMID- 24324483
TI  - Erratum: Green fluorescent protein-based monitoring of endoplasmic reticulum
      redox poise.
AB  - [This corrects the article on p. 108 in vol. 4, PMID: 23781233.].

PMID- 24324485
TI  - Sodium valproate inhibits the growth of human cholangiocarcinoma in vitro and in
      vivo.
AB  - Background. None of treatment options for Cholangiocarcinoma (CCA), including
      surgery, adjuvant radiotherapy and chemotherapy, and ultimately liver
      transplantation, have been shown to substantially improve the survival rate in
      patients with CCA. Valproic acid (VPA), a histone deacetylase inhibitor, has been
      shown to display potent antitumor effects. In this study, sodium valproate, the
      clinically available form of VPA, was tested for its ability to inhibit the
      growth of cholangiocarcinoma cells, both in vitro and in vivo. Materials and
      Methods. Cholangiocarcinoma cells (TFK-1, QBC939, and CCLP1) of different origins
      were treated with sodium valproate to determine their effects on cell
      proliferation and differentiation, cell cycle regulation, apoptosis, and
      autophagy. The in vivo effects of sodium valproate on cholangiocarcinoma growth
      were assessed using a xenograft mouse model injected with TFK-1 cells. Results.
      Sodium valproate inhibited cholangiocarcinoma cell growth by inducing cell cycle
      arrest, cell differentiation, and apoptosis; sodium valproate effects were
      independent of autophagy. Tumor growth inhibition was also observed in vivo using
      TFK-1 xenografts. Conclusion. The in vitro and in vivo outcomes provide
      preclinical rationale for clinical evaluation of sodium valproate, alone or in
      combination with other drugs, to improve patient outcome in cholangiocarcinoma. 

PMID- 24324486
TI  - Covered metal stenting for malignant lower biliary stricture with pancreatic duct
      obstruction: is endoscopic sphincterotomy needed?
AB  - Aims. To evaluate the need for endoscopic sphincterotomy (EST) before covered
      self-expandable metal stent (CSEMS) deployment for malignant lower biliary
      stricture with pancreatic duct obstruction. Methods. This study included 79
      patients who underwent CSEMS deployment for unresectable malignant lower biliary
      stricture with pancreatic duct obstruction. Treatment outcomes and complications
      were compared between 38 patients with EST before CSEMS deployment (EST group)
      and 41 without EST (non-EST group). Results. The technical success rates were
      100% in both the EST and the non-EST group. The incidence of pancreatitis was
      2.6% in the EST, and 2.4% in the non-EST group (P = 0.51). The incidences of
      overall complications were 18.4% and 14.6%, respectively, (P = 0.65). Within the
      non-EST groups, the incidence of pancreatitis was 0% in patients with fully
      covered stent deployment and 3.6% in those with partially covered stent
      deployment (P = 0.69). In the multivariate analysis, younger age (P = 0.003, OR
      12) and nonpancreatic cancer (P = 0.001, OR 24) were significant risk factors for
      overall complications after CSEMS deployment. EST was not identified as a risk
      factor. Conclusions. EST did not reduce the incidence of pancreatitis after CSEMS
      deployment in patients of unresectable distal malignant obstruction with
      pancreatic duct obstruction. 

PMID- 24324487
TI  - Surveillance of HCC Patients after Liver RFA: Role of MRI with Hepatospecific
      Contrast versus Three-Phase CT Scan-Experience of High Volume Oncologic
      Institute.
AB  - Purpose. To compare the diagnostic accuracy of hepatospecific contrast-enhanced
      MRI versus triple-phase CT scan after radiofrequency ablation (RFA) in
      hepatocellular carcinoma (HCC) patients. Methods. Thirty-four consecutive HCC
      patients (42 hepatic nodules) were treated with percutaneous RFA and underwent MR
      and CT scans. All patients were enrolled in a research protocol that included CT
      with iodized contrast medium injection and MR with hepatospecific contrast medium
      injection. All patients were restaged within four weeks and at 3 months from
      ablation. The images were reviewed by four different radiologists to evaluate
      tumor necrosis, residual or recurrence disease, and evidence of new foci.
      Results. Thirty-two nodules were necrotic after treatment; 10 showed residual
      disease. Six new HCCs were identified. At first month followup CT has identified
      34 necrotic lesions and 8 residual diseases; no new foci were recognized. At MRI
      instead, 32 complete necrotic lesions were identified, 10 lesions showed residual
      disease, and 2 new HCCs were found. At three months, CT demonstrated 33
      completely necrotic lesions, 9 residual diseases, and 2 new HCCs. MR showed 31
      complete necrotic lesions, 11 cases of residual disease, and 6 new HCCs.
      Conclusions. Hepatospecific contrast-enhanced MRI is more effective than
      multiphase CT in assessment of HCC treated with RFA. 

PMID- 24324484
TI  - NFkappaB signaling regulates embryonic and adult neurogenesis.
AB  - Both embryonic and adult neurogenesis involves the self-renewal/proliferation,
      survival, migration and lineage differentiation of neural stem/progenitor cells.
      Such dynamic process is tightly regulated by intrinsic and extrinsic factors and
      complex signaling pathways. Misregulated neurogenesis contributes much to a large
      range of neurodevelopmental defects and neurodegenerative diseases. The signaling
      of NFkappaB regulates many genes important in inflammation, immunity, cell
      survival and neural plasticity. During neurogenesis, NFkappaB signaling mediates
      the effect of numerous niche factors such as cytokines, chemokines, growth
      factors, extracellular matrix molecules, but also crosstalks with other signaling
      pathways such as Notch, Shh, Wnt/beta-catenin. This review summarizes current
      progress on the NFkappaB signaling in all aspects of neurogenesis, focusing on
      the novel role of NFkappaB signaling in initiating early neural differentiation
      of neural stem cells and embryonic stem cells.

PMID- 24324488
TI  - Is Occult Obscure Gastrointestinal Bleeding a Definite Indication for Capsule
      Endoscopy? A Retrospective Analysis of Diagnostic Yield in Patients with Occult
      versus Overt Bleeding.
AB  - Background/Aim. Usefulness of capsule endoscopy (CE) for diagnosing small-bowel
      lesions in patients with obscure gastrointestinal bleeding (OGIB) has been
      reported. Most reports have addressed the clinical features of overt OGIB, with
      few addressing occult OGIB. We aimed to clarify whether occult OGIB is a definite
      indication for CE. Methods. We retrospectively compared the cases of 102 patients
      with occult OGIB and 325 patients with overt OGIB, all having undergone CE. The
      diagnostic yield of CE and identification of various lesion types were determined
      in cases of occult OGIB versus overt OGIB. Results. There was no significant
      difference in diagnostic yield between occult and overt OGIB. The small-bowel
      lesions in cases of occult OGIB were diagnosed as ulcer/erosive lesions (n = 18,
      18%), vascular lesions (n = 11, 11%), and tumors (n = 4, 3%), and those in cases
      of overt OGIB were diagnosed as ulcer/erosive lesions (n = 51, 16%), vascular
      lesions (n = 31, 10%), and tumors (n = 20, 6%). Conclusion. CE detection rates
      and CE identification of various small-bowel diseases do not differ between
      patients with occult versus overt OGIB. CE should be actively performed for
      patients with either occult or overt OGIB. 

PMID- 24324489
TI  - The association of postcardiac surgery acute kidney injury with intraoperative
      systolic blood pressure hypotension.
AB  - Background. Postoperative acute kidney injury (AKI) is associated with high
      mortality and substantial cost after aortocoronary bypass graft (CABG) surgery.
      We tested the hypothesis that intraoperative systolic blood pressure variation is
      associated with postoperative AKI. Methods. We gathered demographic, procedural,
      blood pressure, and renal outcome data for 7,247 CABG surgeries at a single
      institution between 1996 and 2005. A development/validation cohort methodology
      was randomly divided (66% and 33%, resp.). Peak postoperative serum creatinine
      rise relative to baseline (%DeltaCr) was the primary AKI outcome variable.
      Markers reflective of intraoperative systolic blood pressure variation were
      derived for each patient including (1) peak and nadir values (absolute and
      relative to baseline) and (2) excursion episodes beyond selected thresholds (by
      duration, frequency, and duration * degree). Each marker of systolic blood
      pressure variation was then separately evaluated for association with AKI using
      linear regression models with adjustment for several known risk factors (age,
      aprotinin use, congestive heart failure, previous myocardial infarction, baseline
      creatinine, bypass time, diabetes, weight, concomitant valve surgery, gender, and
      preoperative pulse pressure). Results. An association was identified between
      systolic blood pressure relative to baseline and postoperative AKI (P < 0.006).
      Conclusions. In CABG surgery patients, intraoperative systolic blood pressure
      decrease relative to baseline systolic blood pressure is independently associated
      with postoperative AKI. 

PMID- 24324490
TI  - Effect of gelam honey on the oxidative stress-induced signaling pathways in
      pancreatic hamster cells.
AB  - Background. Oxidative stress induced by reactive oxygen and nitrogen species is
      critically involved in the impairment of beta -cell function during the
      development of diabetes. Methods. HIT-T15 cells were cultured in 5% CO2 and then
      preincubated with Gelam honey extracts (20, 40, 60, and 80 ug/mL) as well as
      quercetin (20, 40, 60, and 80 uM), prior to stimulation by 20 and 50 mM of
      glucose. Cell lysate was collected to determine the effect of honey extracts and
      quercetin on the stress activated NF- kappa B, MAPK pathways, and the Akt
      (ser473) activated insulin signaling pathway. Results. HIT-T15 cells cultured
      under hyperglycemic conditions demonstrated insulin resistance with a significant
      increase in the levels of MAPK, NF- kappa B, and IRS-1 serine phosphorylation
      (ser307); however, Akt expression and insulin contents are significantly
      decreased. Pretreatment with quercetin and Gelam honey extract improved insulin
      resistance and insulin content by reducing the expression of MAPK, NF- kappa B,
      and IRS-1 serine phosphorylation (ser307) and increasing the expression of Akt
      significantly. Conclusion. Gelam honey-induced differential expression of MAPK,
      NF- kappa B, IRS-1 (ser307), and Akt in HIT-T15 cells shows that Gelam honey
      exerts protective effects against diabetes- and hyperglycemia-induced oxidative
      stress by improving insulin content and insulin resistance. 

PMID- 24324491
TI  - Adenovirus-36 seropositivity and its relation with obesity and metabolic profile
      in children.
AB  - The human adenovirus 36 (Ad-36) is causally and correlatively associated in
      animals and humans, respectively, with increased adiposity and altered metabolic
      profile. In previous studies, the relationship between Ad-36 seropositivity with
      obesity was established in adults and children. We evaluated the association of
      positive antibodies to Ad-36 with obesity and metabolic profile in Mexican
      children. Seventy-five children with normal-weight and 82 with obesity were
      studied in this research. All children had a clinic assessment which included
      weight, height, body circumferences, and skinfold thickness. Laboratory analyzes
      included triglycerides, total cholesterol, high-density lipoprotein, low-density
      lipoprotein, and glucose and insulin levels. An enzyme-linked immunosorbent assay
      (ELISA) was used to determine the antibodies to Ad-36 in the serum samples. The
      overall Ad-36 seroprevalence was 73.9%. Ad-36 seropositivity had a higher
      prevalence in obese children than in normal weight group (58.6 versus 41.4%, P =
      0.007). Ad-36 seropositivity was associated with obesity (OR = 2.66, P = 0.01)
      and high-density lipoprotein <40 mg/dL (OR = 2.85, P = 0.03). The Ad-36
      seropositive group had greater risk of 4 metabolic abnormalities compared with
      those children without none alteration. In summary, Ad-36 seropositivity was
      associated with obesity and low HDL-c levels in the sample of children studied. 

PMID- 24324493
TI  - A Double-Blind, Placebo Controlled, Randomized Trial to Assess the Impact of a
      Monthly Administration of 50,000 IU of Vitamin D3 for 6 Months on Serum Levels of
      25-Hydroxyvitamin D in Healthy Young Adults.
AB  - In this double blind, unicentre, randomized, placebo controlled study, we
      evaluated the changes in 25-hydroxyvitamin D (25(OH)D) serum levels in 150 young
      Belgian adults (18-30 years), monthly supplemented with 50,000 IU of vitamin D
      (VTD) or placebo for 6 months, from November 2010 to May 2011. At T0, 30% of the
      population presented 25(OH)D serum levels below 20 ng/mL. In the VTD-treated
      group, mean serum levels increased from 21.2 +/- 8.2 to 30.6 +/- 8.8 ng/mL (P <
      0.001) at T3mo and to 36.0 +/- 9.2 ng/mL (P < 0.001) at T6mo. Despite documented
      VTD intake, no changes in serum levels were, however, observed in 10% of the
      treated group. In the placebo group, mean 25(OH)D serum levels decreased from
      22.8 +/- 8.5 to 14.0 +/- 6.9 ng/mL at T3mo (P < 0.001) but returned to values not
      significantly different from those observed at T0 (23.5 +/- 8.6 ng/mL) at T6mo.
      No difference between serum calcium levels was observed between the groups
      throughout the study. In conclusion, monthly supplementation with 50,000 UI of
      VTD in winter can warrant serum 25(OH)D levels above 20 ng/mL in 96.2% of those
      healthy young adults without inducing unacceptably high 25(OH)D concentration.
      This supplementation is safe and may be proposed without 25(OH)D testing. 

PMID- 24324492
TI  - Estrogens and spermiogenesis: new insights from type 1 cannabinoid receptor
      knockout mice.
AB  - Spermatogenesis is a complex mechanism which allows the production of male
      gametes; it consists of mitotic, meiotic, and differentiation phases.
      Spermiogenesis is the terminal differentiation process during which haploid round
      spermatids undergo several biochemical and morphological changes, including
      extensive remodelling of chromatin and nuclear shape. Spermiogenesis is under
      control of endocrine, paracrine, and autocrine factors, like gonadotropins and
      testosterone. More recently, emerging pieces of evidence are suggesting that,
      among these factors, estrogens may have a role. To date, this is a matter of
      debate and concern because of the agonistic and antagonistic estrogenic effects
      that environmental chemicals may have on animal and human with damaging outcome
      on fertility. In this review, we summarize data which fuel this debate, with a
      particular attention to our recent results, obtained using type 1 cannabinoid
      receptor knockout male mice as animal model. 

PMID- 24324495
TI  - Male Central Precocious Puberty: Serum Profile of Anti-Mullerian Hormone and
      Inhibin B before, during, and after Treatment with GnRH Analogue.
AB  - We aimed to describe the functional changes of Sertoli cells, based on the
      measurement of serum anti-Mullerian hormone (AMH) and inhibin B during treatment
      with GnRHa and after its withdrawal in boys with central precocious puberty. Six
      boys aged 0.8 to 5.5 yr were included. AMH was low at diagnosis in patients >1 yr
      but within the normal range in younger patients. AMH increased to normal
      prepubertal levels during treatment. After GnRHa withdrawal, AMH declined
      concomitantly with the rise in serum testosterone. At diagnosis, inhibin B was
      elevated and decreased throughout therapy, remaining in the upper normal
      prepubertal range. In patients with testicular volume above 4 mL AMH remained
      higher in spite of suppressed FSH. After treatment withdrawal, inhibin B rose
      towards normal pubertal levels. In conclusion, AMH did not decrease in patients
      <1 yr reflecting the lack of androgen receptor expression in Sertoli cells in
      early infancy. Serum inhibin B might result from the contribution of two sources:
      the mass of Sertoli cells and the stimulation exerted by FSH. Sertoli cell
      markers might provide additional tools for the diagnosis and treatment followup
      of boys with central precocious puberty. 

PMID- 24324494
TI  - Pharmacogenetics of oral antidiabetic drugs.
AB  - Oral antidiabetic drugs (OADs) are used for more than a half-century in the
      treatment of type 2 diabetes. Only in the last five years, intensive research has
      been conducted in the pharmacogenetics of these drugs based mainly on the
      retrospective register studies, but only a handful of associations detected in
      these studies were replicated. The gene variants in CYP2C9, ABCC8/KCNJ11, and
      TCF7L2 were associated with the effect of sulfonylureas. CYP2C9 encodes
      sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9, ABCC8 and KCNJ11 genes
      encode proteins constituting ATP-sensitive K(+) channel which is a therapeutic
      target for sulfonylureas, and TCF7L2 is a gene with the strongest association
      with type 2 diabetes. SLC22A1, SLC47A1, and ATM gene variants were repeatedly
      associated with the response to metformin. SLC22A1 and SLC47A1 encode metformin
      transporters OCT1 and MATE1, respectively. The function of a gene variant near
      ATM gene identified by a genome-wide association study is not elucidated so far.
      The first variant associated with the response to gliptins is a polymorphism in
      the proximity of CTRB1/2 gene which encodes chymotrypsinogen. Establishment of
      diabetes pharmacogenetics consortia and reduction in costs of genomics might lead
      to some significant clinical breakthroughs in this field in a near future. 

PMID- 24324496
TI  - Titrimetric and Spectrophotometric Methods for the Assay of Ketotifen Using
      Cerium(IV) and Two Reagents.
AB  - One titrimetric and two spectrophotometric methods are described for the
      determination of ketotifen fumarate (KTF) in bulk drug and in tablets using
      cerium(IV) as the oxidimetric agent. In titrimetry (method A), the drug was
      treated with a measured excess of cerium(IV) in H2SO4 medium and after a standing
      time of 10 min, the surplus oxidant was determined by back titration with
      iron(II). The spectrophotometric procedures involve addition of a known excess of
      cerium(IV) to KTF in acid medium followed by the determination of unreacted
      oxidant by reacting with either p-dimethyl amino benzaldehyde and measuring the
      resulting colour at 460 nm (method B) or o-dianisidine and subsequent measurement
      of the absorbance of coloured product at 470 nm (method C). Titrimetric assay is
      based on a 1 : 2 reaction stoichiometry between KTF and cerium(IV) and the method
      is applicable over 2-18 mg range. In spectrophotometry, regression analysis of
      Beer's law plots showed a good correlation in 0.4-8.0 and 0.4-10.0 g mL(-1) KTF
      ranges for method B and method C, respectively, and the corresponding molar
      absorptivity coefficients are calculated to be 4.0 * 10(4) and 3.7 * 10(4) L mol(
      1) cm(-1). 

PMID- 24324498
TI  - ER Dysfunction and Protein Folding Stress in ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is the most frequent paralytic disease in
      adults. Most ALS cases are considered sporadic with no clear genetic component.
      The disruption of protein homeostasis due to chronic stress responses at the
      endoplasmic reticulum (ER) and the accumulation of abnormal protein inclusions
      are extensively described in ALS mouse models and patient-derived tissue. Recent
      studies using pharmacological and genetic manipulation of the unfolded protein
      response (UPR), an adaptive reaction against ER stress, have demonstrated a
      complex involvement of the pathway in experimental models of ALS. In addition,
      quantitative changes in ER stress-responsive chaperones in body fluids have been
      proposed as possible biomarkers to monitor the disease progression. Here we
      review most recent advances attributing a causal role of ER stress in ALS. 

PMID- 24324499
TI  - Sinus fungus ball in the Japanese population: clinical and imaging
      characteristics of 104 cases.
AB  - Sinus fungus ball is defined as noninvasive chronic fungal rhinosinusitis
      occurring in immunocompetent patients with regional characteristics. The clinical
      and imaging characteristics of paranasal sinus fungus ball were retrospectively
      investigated in 104 Japanese patients. All patients underwent endoscopic sinus
      surgery. Preoperative computed tomography (CT), magnetic resonance (MR) imaging,
      age, sex, chief complaint, causative fungus, and clinical outcome were analyzed.
      Patients were aged from 25 to 79 years (mean 58.8 years). Female predominance was
      noted (58.7%). Most common symptoms were nasal discharge and facial pain. CT
      showed high density area in 82.0% of the cases (82/100), whereas T2-weighted MR
      imaging showed low intensity area in 100% of the cases (32/32). Histological
      examination showed that most causative agents were Aspergillus species (94.2%
      (98/104)). Culture test was positive for 16.7% (11/66). Recurrence was found in
      3.2% (3/94). Older age and female predominance were consistent with previous
      reports. MR imaging is recommended to confirm the diagnosis. 

PMID- 24324500
TI  - A Giant Ureteral Stone without Underlying Anatomic or Metabolic Abnormalities: A
      Case Report.
AB  - A 28-year old man presented with left flank pain and dysuria. Plain abdominal
      film and computed tomography showed a left giant ureteral stone measuring 11.5 cm
      causing ureteral obstruction and other stones 2.5 cm in size in the lower pole of
      ipsilateral kidney and 7 mm in size in distal part of right ureter. A left
      ureterolithotomy was performed and then a double J stent was inserted into the
      ureter. The patient was discharged from the hospital 4 days postoperatively with
      no complications. Stone analysis was consistent with magnesium ammonium phosphate
      and calcium oxalate. Underlying anatomic or metabolic abnormalities were not
      detected. One month after surgery, right ureteral stone passed spontaneously,
      left renal stone moved to distal ureter, and it was removed by ureterolithotomy.
      Control intravenous urography and cystography demonstrated unobstructed bilateral
      ureter and the absence of vesicoureteral reflux. 

PMID- 24324497
TI  - Small-molecule theranostic probes: a promising future in neurodegenerative
      diseases.
AB  - Prion diseases are fatal neurodegenerative illnesses, which include Creutzfeldt
      Jakob disease in humans and scrapie, chronic wasting disease, and bovine
      spongiform encephalopathy in animals. They are caused by unconventional
      infectious agents consisting primarily of misfolded, aggregated, beta -sheet-rich
      isoforms, denoted prions, of the physiological cellular prion protein (PrP(C)).
      Many lines of evidence suggest that prions (PrP(Sc)) act both as a template for
      this conversion and as a neurotoxic agent causing neuronal dysfunction and cell
      death. As such, PrP(Sc) may be considered as both a neuropathological hallmark of
      the disease and a therapeutic target. Several diagnostic imaging probes have been
      developed to monitor cerebral amyloid lesions in patients with neurodegenerative
      disorders (such as Alzheimer's disease, Parkinson's disease, and prion disease).
      Examples of these probes are Congo red, thioflavin T, and their derivatives. We
      synthesized a series of styryl derivatives, denoted theranostics, and studied
      their therapeutic and/or diagnostic potentials. Here we review the salient traits
      of these small molecules that are able to detect and modulate aggregated forms of
      several proteins involved in protein misfolding diseases. We then highlight the
      importance of further studies for their practical implications in therapy and
      diagnostics. 

PMID- 24324501
TI  - Lung cancer risk and past exposure to emissions from a large steel plant.
AB  - We studied the spatial distribution of cancer incidence rates around a large
      steel plant and its association with historical exposure. The study population
      was close to 600,000. The incidence data was collected for 1995-2006. From
      historical emission data the air pollution concentrations for polycyclic aromatic
      hydrocarbons (PAH) and metals were modelled. Data were analyzed using Bayesian
      hierarchical Poisson regression models. The standardized incidence ratio (SIR)
      for lung cancer was up to 40% higher than average in postcodes located in two
      municipalities adjacent to the industrial area. Increased incidence rates could
      partly be explained by differences in socioeconomic status (SES). In the highest
      exposure category (approximately 45,000 inhabitants) a statistically significant
      increased relative risk (RR) of 1.21 (1.01-1.43) was found after adjustment for
      SES. The elevated RRs were similar for men and women. Additional analyses in a
      subsample of the population with personal smoking data from a recent survey
      suggested that the observed association between lung cancer and plant emission,
      after adjustment for SES, could still be caused by residual confounding.
      Therefore, we cannot indisputably conclude that past emissions from the steel
      plant have contributed to the increased risk of lung cancer. 

PMID- 24324502
TI  - An Integrated Quantitative Methodology to Longitudinally Characterize Complex
      Dynamic Processes Associated with Ovarian Aging and the Menopausal Transition.
AB  - An integrative methodology is developed to characterize the complex patterns of
      change in highly variable dynamic biological processes. The method permits
      estimatation of the population mean profile, multiple change points and length of
      time-windows defined by any two change points of interest using a semi-/non
      parametric stochastic mixed effect model and a Bayesian Modeling Average (BMA)
      approach to account for model uncertainty. It also allows estimation of the mean
      rate of change of sub-processes by fitting piecewise linear mixed effect models.
      The methodology is applied to characterize the stages of female ovarian aging and
      the menopausal transition defined by hormone measures of estradiol (E2) and
      follicle stimulating hormone (FSH) from two large-scale epidemiological studies
      with community-based longitudinal designs and ethnic diversity.

PMID- 24324503
TI  - Association of human leukocyte antigen class I polymorphism with spontaneous
      clearance of hepatitis B surface antigen in Qidong Han population.
AB  - AIM: To investigate whether HLA class I polymorphisms could influence the
      clearance of hepatitis B surface antigen (HBsAg) in Qidong Han population.
      METHODS: We genotyped HLA-A, -B, and -C loci of 448 individuals with HBV
      persistent infection and 140 persons with spontaneous clearance of HBsAg by
      polymerase chain reaction with sequencing based typing (PCR/SBT). All the
      individuals were unrelated males enrolled from Qidong Han population and were
      followed up for 10 years. RESULTS: The frequency of HLA-A*33:03:01G was increased
      in persistent HBV infection group (P value is 0.028), while frequency of HLA
      B*13:01:01G was increased in HBsAg clearance group (P value is 0.0004).
      CONCLUSION: These findings suggested that the host HLA class I polymorphism is an
      important factor in determining the outcomes of HBV infection.

PMID- 24324504
TI  - Mesoporous silicon microparticles enhance MHC class I cross-antigen presentation
      by human dendritic cells.
AB  - The mesoporous silicon microparticles (MSMPs) are excellent vehicles for
      releasing molecules inside the cell. The aim of this work was to use MSMPs to
      deliver viral specific MHC class I restricted epitopes into human antigen
      presenting cells (monocyte derived dendritic cells, MDDCs) to facilitate their
      capture, processing, and presentation to CD8+ (cytotoxic) T lymphocytes. We show
      for the first time that MSMPs vehiculation of antigenic peptides enhances their
      MHC class I presentation by human MDDCs to CD8 T lymphocytes.

PMID- 24324505
TI  - Allergenic characterization of new mutant forms of Pru p 3 as new immunotherapy
      vaccines.
AB  - Nowadays, treatment of food allergy only considered the avoidance of the specific
      food. However, the possibility of cross-reactivity makes this practice not very
      effective. Immunotherapy may exhibit as a good alternative to food allergy
      treatment. The use of hypoallergenic molecules with reduced IgE binding capacity
      but with ability to stimulate the immune system is a promising tool which could
      be developed for immunotherapy. In this study, three mutants of Pru p 3, the
      principal allergen of peach, were produced based on the described mimotope and T
      cell epitopes, by changing the specific residues to alanine, named as Pru p 3.01,
      Pru p 3.02, and Pru p 3.03. Pru p 3.01 showed very similar allergenic activity as
      the wild type by in vitro assays. However, Pru p 3.02 and Pru p 3.03 presented
      reduced IgE binding with respect to the native form, by in vitro, ex vivo, and in
      vivo assays. In addition, Pru p 3.03 had affected the IgG4 binding capacity and
      presented a random circular dichroism, which was reflected in the nonrecognition
      by specific antibodies anti-Pru p 3. Nevertheless, both Pru p 3.02 and Pru p 3.03
      maintained the binding to IgG1 and their ability to activate T lymphocytes. Thus,
      Pru p 3.02 and Pru p 3.03 could be good candidates for potential immunotherapy in
      peach-allergic patients. 

PMID- 24324506
TI  - Role of toll-like receptor 4 on lupus lung injury and atherosclerosis in LPS
      challenge ApoE-/- mice.
AB  - To investigate the pathologic mechanisms of toll-like receptor 4 (TLR4) in lung
      injury and atherosclerosis, ApoE-/- or wild-type mice were intraperitoneally
      administered saline, lipopolysaccharides (LPS), or LPS plus TAK-242 (TLR4
      inhibitor), respectively, twice a week for 4 weeks. Serum autoantibody of
      antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and cytokines
      of interferon-gamma (IFN-gamma), tumor necrosis factor (TNF-alpha ), and
      interleukin-1 (IL-1beta) were assessed by ELISA. Hematoxylin and eosin (HE) and
      Perl's stains for lung pathomorphology as well as HE staining for atherosclerosis
      were employed. TLR4 in macrophages was detected by double immunofluorescent
      staining. While protein expressions of TLR4, nuclear factor-kappa B p65 (NF
      kappaB p65), and B cell activating factor belonging to the TNF family (BAFF) were
      examined by immunohistochemistry. We found that serum autoantibody (ANA and anti
      dsDNA), cytokines (IFN-gamma, TNF-alpha, IL-1beta), lung inflammation, and intima
      media thickness in brachiocephalic artery were obviously increased after LPS
      challenge in both genotypes, but to a lesser extent in wild-type strains. And
      those alterations were alleviated by coadministration of LPS and TAK-242.
      Mechanistically, upregulation of TLR4, NF-kappab, and BAFF was involved. We
      concluded that TLR4/NF-kappab/BAFF in macrophages might be a possible common
      autoimmune pathway that caused lung injury and atherosclerosis. TLR4 signal will
      be a therapeutic target in atherosclerosis and immune-mediated lung injury.

PMID- 24324507
TI  - Modification of intestinal microbiota and its consequences for innate immune
      response in the pathogenesis of campylobacteriosis.
AB  - Campylobacter jejuni is the leading cause of bacterial food-borne gastroenteritis
      in the world, and thus one of the most important public health concerns. The
      initial stage in its pathogenesis after ingestion is to overcome colonization
      resistance that is maintained by the human intestinal microbiota. But how it
      overcomes colonization resistance is unknown. Recently developed humanized
      gnotobiotic mouse models have provided deeper insights into this initial stage
      and host's immune response. These studies have found that a fat-rich diet
      modifies the composition of the conventional intestinal microbiota by increasing
      the Firmicutes and Proteobacteria loads while reducing the Actinobacteria and
      Bacteroidetes loads creating an imbalance that exposes the intestinal epithelial
      cells to adherence. Upon adherence, deoxycholic acid stimulates C. jejuni to
      synthesize Campylobacter invasion antigens, which invade the epithelial cells. In
      response, NF- kappa B triggers the maturation of dendritic cells. Chemokines
      produced by the activated dendritic cells initiate the clearance of C. jejuni
      cells by inducing the actions of neutrophils, B-lymphocytes, and various subsets
      of T-cells. This immune response causes inflammation. This review focuses on the
      progress that has been made on understanding the relationship between intestinal
      microbiota shift, establishment of C. jejuni infection, and consequent immune
      response. 

PMID- 24324508
TI  - Influence of the cholinergic system on the immune response of teleost fishes:
      potential model in biomedical research.
AB  - Fishes are the phylogenetically oldest vertebrate group, which includes more than
      one-half of the vertebrates on the planet; additionally, many species have
      ecological and economic importance. Fish are the first evolved group of organisms
      with adaptive immune mechanisms; consequently, they are an important link in the
      evolution of the immune system, thus a potential model for understanding the
      mechanisms of immunoregulation. Currently, the influence of the neurotransmitter
      acetylcholine (ACh) on the cells of the immune system is widely studied in
      mammalian models, which have provided evidence on ACh production by immune cells
      (the noncholinergic neuronal system); however, these neuroimmunomodulation
      mechanisms in fish and lower vertebrates are poorly studied. Therefore, the
      objective of this review paper was to analyze the influence of the cholinergic
      system on the immune response of teleost fish, which could provide information
      concerning the possibility of bidirectional communication between the nervous and
      immune systems in these organisms and provide data for a better understanding of
      basic issues in neuroimmunology in lower vertebrates, such as bony fishes. Thus,
      the use of fish as a model in biomedical research may contribute to a better
      understanding of human diseases and diseases in other animals. 

PMID- 24324509
TI  - Notch signaling and T-helper cells in EAE/MS.
AB  - The Notch signaling pathway preservation across species hints to the
      indispensable role it plays during evolution. Over the last decade the science
      community has extensively studied the Notch signaling pathway, with Notch
      emerging as a key player in embryogenesis, tissue homeostasis, angiogenesis, and
      immunoregulation. Multiple sclerosis (MS) is an incurable yet treatable
      autoimmune chronic inflammatory disease of the central nervous system. The aim of
      this review is to provide a brief description of the Notch signaling pathway, and
      summarize the current literature implicating Notch in the pathogenesis of MS. 

PMID- 24324510
TI  - Efficacy of abatacept for arthritis in patients with an overlap syndrome between
      rheumatoid arthritis and systemic lupus erythematosus.
AB  - INTRODUCTION: This study aimed to investigate the efficacy of abatacept for
      arthritis in patients with rhupus, an overlap syndrome between rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Patients who
      fulfilled both the 2010 ACR/EULAR criteria for RA classification and the 1997 ACR
      revised criteria for classification of SLE and received abatacept treatment for
      arthritis were retrospectively studied. RESULTS: Six rhupus patients who
      fulfilled the inclusion criteria above were identified. All patients had active
      arthritis despite receiving antirheumatic drugs including methotrexate when
      abatacept was initiated. Clinical Disease Activity Index (CDAI) significantly
      decreased between baseline and 12 weeks (P = 0.028) and remained low through 24
      weeks. All patients achieved either a good or moderate response according to the
      EULAR response criteria at 24 weeks. Health Assessment Questionnaire-Disability
      Index (HAQ-DI) also significantly decreased between baseline and 24 weeks (P =
      0.043). In addition, the levels of immunoglobulin G and anti-DNA antibody
      significantly decreased between baseline and 24 weeks (P = 0.028 and P = 0.043,
      resp.). CONCLUSIONS: Treatment with abatacept is likely to be efficacious in
      patients with rhupus whose arthritis is refractory to methotrexate. In addition,
      abatacept may have a moderate effect on abnormal antibody production in rhupus
      patients.

PMID- 24324512
TI  - Ten years' research on a cardiovascular tonic: a comprehensive approach-from
      quality control and mechanisms of action to clinical trial.
AB  - Objective. Mortality arising from cardiovascular pathologies remains one of the
      highest. Maintenance of cardiovascular health therefore remains a universal
      concern. Interventional therapies and medications have made impressive advances,
      but preventive measures would be of the same importance. Method. Ten years'
      search for a simple herbal formula has resulted in a two-herb combination,
      consisting of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix.
      The formula has been studied extensively on cardiovascular biological platforms
      and then put on three clinical trials. Results. In the laboratory, the formula
      was found to have the biological effects of anti-inflammation, anti-oxidation,
      anti-foam cell formation on vascular endothelium, and vasodilation. Clinical
      trials using ultrasonic carotid intima thickness as a surrogate marker showed
      very significant benefits. No significant adverse effects were encountered.
      Conclusion. It is therefore recommended that the herbal formula could be used as
      an adjuvant therapy in cardiac patients under treatment or as a preventive agent
      among the susceptible. 

PMID- 24324511
TI  - Design of peptide immunotherapies for MHC Class-II-associated autoimmune
      disorders.
AB  - Autoimmune disorders, that occur when autoreactive immune cells are induced to
      activate their responses against self-tissues, affect one percent of the world
      population and represent one of the top 10 leading causes of death. The major
      histocompatibility complex (MHC) is a principal susceptibility locus for many
      human autoimmune diseases, in which self-tissue antigens providing targets for
      pathogenic lymphocytes are bound to HLA molecules encoded by disease-associated
      alleles. In spite of the attempts to design strategies for inhibition of antigen
      presentation targeting the MHC-peptide/TCR complex via generation of blocking
      antibodies, altered peptide ligands (APL), or inhibitors of costimulatory
      molecules, potent therapies with minimal side effects have yet to be developed.
      Copaxone (glatiramer acetate, GA) is a random synthetic amino acid copolymer that
      reduces the relapse rate by about 30% in relapsing-remitting multiple sclerosis
      (MS) patients. Based on the elucidated binding motifs of Copaxone and of the
      anchor residues of the immunogenic myelin basic protein (MBP) peptide to HLA-DR
      molecules, novel copolymers have been designed and proved to be more effective in
      suppressing MS-like disease in mice. In this report, we describe the rationale
      for design of second-generation synthetic random copolymers as candidate drugs
      for a number of MHC class-II-associated autoimmune disorders. 

PMID- 24324513
TI  - Acupuncture in practice: investigating acupuncturists' approach to treating
      infantile colic.
AB  - Infantile colic is common, but no safe and effective conventional treatment
      exists. The use of acupuncture has increased despite weak evidence. This
      practitioner survey explores and discusses how infantile colic is regarded and
      treated in Traditional Chinese Medicine (TCM). The study is based on personal
      communication with 24 acupuncturists from nine countries. These acupuncturists
      specialize in pediatric acupuncture and represent different styles of
      acupuncture. Their experiences are discussed and related to relevant books and
      articles. Informants claimed good results when treating infants with colic. The
      TCM patterns commonly described by informants matched the textbooks to a great
      extent. The most common syndromes were "stagnation of food" and "Spleen Qi Xu."
      Regarding treatment, some informants followed the teachers' and the textbook
      authors' advice on differentiated treatment according to syndrome. The points
      used most often were LI4, ST36, and Sifeng. Other informants treated all infants
      alike in one single point, LI4. The results demonstrate the diversity of TCM. The
      use of acupuncture for infantile colic presents an interesting option, but
      further research is needed in order to optimize the effects and protect infants
      from unnecessary or less effective treatment. 

PMID- 24324514
TI  - Clinical study on the prevention of oxaliplatin-induced neurotoxicity with
      guilongtongluofang: results of a randomized, double-blind, placebo-controlled
      trial.
AB  - Objective. Oxaliplatin-induced peripheral neurotoxicity continues to be a kind of
      frequent dose-limiting toxicity for many cancer patients. This study evaluated
      the preventive effects of Guilongtongluofang on peripheral neurotoxicity induced
      by oxaliplatin in patients with colorectal tumor. Patients and Methods. From May
      2007 to May 2011, we conducted a randomized, double-blind, placebo-controlled
      trial. 120 patients of colorectal cancer treated with adjuvant oxaliplatin-based
      chemotherapy were randomly enrolled into the trial group and the control group.
      The trial group received Guilongtongluofang (at a dose of 200 mL once a day) from
      3 days prior to chemotherapy. The control group received a placebo from 3 days
      prior to chemotherapy. Every 2-week cycle, neurotoxicity was evaluated using
      numeric rating scale for pain intensity and experienced relief. The primary
      endpoint was efficacy measurement which included oxaliplatin-induced
      neurotoxicity and tumor response. The differences of side effects between the two
      groups were also analyzed. Results. The percentage of grades 1-2 neurotoxicity
      was significantly lower in the trial group than that in the control group (13.3%
      versus 20.0%; P < 0.05) after two cycles of treatment. The difference of the
      percentage of neurotoxicity between the two groups was significant after six
      cycles (51.7% versus 70.0%; P < 0.05). Significant difference for the mean time
      to the development of grade 1+ neurotoxicity was found between the two groups
      (9.4 w in the trial group versus 6.5 w in the control group, P < 0.05). The
      cumulative incidence of grade 1 or more sensory neurotoxicity was significantly
      lower in the trial group than that in the control group (P < 0.05). No
      significant differences of tumor response rate were found between the two groups
      the trial group and the control group. No significant difference was found
      between the trial group and the control group (all P > 0.05). Conclusion. This
      study provides evidence that Guilongtongluofang is a promising drug for the
      prevention of oxaliplatin-induced neurotoxicity in patients with colorectal
      cancer, and it does not reduce the efficacy of oxaliplatin. 

PMID- 24324515
TI  - Effect of KIOM-79 on Diabetes-Induced Myocardial Fibrosis in Zucker Diabetic
      Fatty Rats.
AB  - KIOM-79, a herbal mixture of parched Puerariae radix, gingered Magnoliae cortex,
      Glycyrrhizae radix, and Euphorbiae radix, has a strong inhibitory effect on
      advanced glycation end products (AGEs) formation. We investigated the beneficial
      effects of KIOM-79 on cardiac fibrosis in Zucker diabetic fatty (ZDF) rats. KIOM
      79 (50 or 500 mg/kg/day) was orally administered for 13 weeks. AGEs formation and
      collagen expression in the myocardium were assessed by immunohistochemistry. The
      expression levels of the receptor for AGEs (RAGE), transforming growth factor-
      beta 1 (TGF- beta 1), collagen IV, fibronectin, urotensin II, and urotensin II
      receptor were examined in the myocardial tissue of ZDF rats. KIOM-79 treatment at
      500 mg/kg inhibited the accumulation of AGEs, reduced RAGE mRNA and protein
      expression, and reduced the upregulation of cardiac fibrogenic factors, such as
      fibronectin and collagen IV, in heart of ZDF rats. Additionally, KIOM-79
      ameliorated urotensin II/receptor gene expression in the cardiac tissue of ZDF
      rats. Our findings indicate that KIOM-79 diminishes cardiac fibrosis in ZDF rats
      by preventing AGEs accumulation and RAGE overexpression and by modulating the
      cardiac urotensin II/receptor pathway, which decreases the amount of profibrotic
      factors, such as TGF- beta 1, fibronectin, and collagen in cardiac tissue. 

PMID- 24324516
TI  - 7,3',4'-Trihydroxyisoflavone Ameliorates the Development of Dermatophagoides
      farinae-Induced Atopic Dermatitis in NC/Nga Mice.
AB  - Atopic dermatitis is an inflammatory and chronically relapsing skin disorder that
      commonly occurs in children; the number of atopic dermatitis patients is
      increasing. The cause and mechanism of atopic dermatitis have not been defined
      clearly, although many studies are ongoing. Epidemiological studies suggest that
      soybean and its isoflavones have immunoregulatory activities. Here, we report
      that 7,3',4'-trihydroxyisoflavone (7,3',4'-THIF), a major metabolite of daidzin,
      effectively inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor
      necrosis factor (TNF)- alpha , and interleukin (IL)-6 production in RAW 264.7
      cells, and also reduced beta -hexosaminidase secretion in RBL-2H3 cells.
      Moreover, 7,3',4'-THIF significantly reduced scratching time, transepidermal
      water loss, and mast cell infiltration. It also decreased protease-activated
      receptor (PAR)-2 and IL-4 expression and increased filaggrin expression in skin
      lesions of NC/Nga mice. These results suggest that 7,3',4'-THIF improves
      Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice. 

PMID- 24324517
TI  - Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and
      Diabetes: A Review.
AB  - Insulin resistance is a key factor in metabolic disorders like hyperglycemia and
      hyperinsulinemia, which are promoted by obesity and may later lead to Type II
      diabetes mellitus. In recent years, researchers have identified links between
      insulin resistance and many noncommunicable illnesses other than diabetes. Hence,
      studying insulin resistance is of particular importance in unravelling the
      pathways employed by such diseases. In this review, mechanisms involving free
      fatty acids, adipocytokines such as TNF alpha and PPAR gamma and serine kinases
      like JNK and IKK beta , asserted to be responsible in the development of insulin
      resistance, will be discussed. Suggested mechanisms for actions in normal and
      disrupted states were also visualised in several manually constructed diagrams to
      capture an overall view of the insulin-signalling pathway and its related
      components. The underlying constituents of medicinal significance found in the
      Stevia rebaudiana Bertoni plant (among other plants that potentiate
      antihyperglycemic activities) were explored in further depth. Understanding these
      factors and their mechanisms may be essential for comprehending the progression
      of insulin resistance towards the development of diabetes mellitus. 

PMID- 24324518
TI  - Ethanolic Extract of Polish Propolis: Chemical Composition and TRAIL-R2 Death
      Receptor Targeting Apoptotic Activity against Prostate Cancer Cells.
AB  - Propolis possesses chemopreventive properties through direct anticancer and
      indirect immunomodulatory activities. Tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) plays a significant role in immunosurveillance and
      defense against cancer cells. TRAIL triggers apoptosis upon binding to TRAIL-R1
      (DR4) and TRAIL-R2 (DR5) death receptors expressed on cancer cell surface. The
      activation of TRAIL apoptotic signaling is considered an attractive option for
      cancer prevention. However, as more tumor cells are reported to be resistant to
      TRAIL-mediated death, it is important to develop new strategies to overcome this
      resistance. The aim of this study was to investigate the chemical composition and
      proapoptotic mechanism of ethanolic extract of Polish propolis (EEP-P) against
      cancer cells. The identification and quantification of phenolic compounds in
      propolis extract were performed using HPLC-DAD and UPLC-Q-TOF-MS methods. TRAIL
      resistant LNCaP prostate cancer cells were treated with EEP-P and TRAIL.
      Cytotoxicity was measured by MTT and LDH assays. Apoptosis was detected using
      annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death
      receptors expression was analyzed using flow cytometry. Pinobanksin, chrysin,
      methoxyflavanone, p-coumaric acid, ferulic acid and caffeic acid were the main
      phenolics found in EEP-P. Propolis sensitized LNCaP cells through upregulation of
      TRAIL-R2. These results suggest that EEP-P supports TRAIL-mediated
      immunochemoprevention in prostate cancer cells. 

PMID- 24324519
TI  - Concurrent Complementary and Alternative Medicine CAM and Conventional
      Rehabilitation Therapy in the Management of Children with Developmental
      Disorders.
AB  - Background. We investigated the concurrent use of conventional rehabilitations
      and complementary and alternative medicine (CAM) therapies for the long-term
      management of children with developmental disorders (DDs). Methods. The parents
      or caregivers of 533 children with DDs (age range, 1-19 years) who visited the
      rehabilitation centers were surveyed using in depth face-to-face interviews.
      Results. Of the 533 patients enrolled, 520 completed the questionnaire (97%
      response rate). A total of 292 (56%) children were receiving multiple therapies,
      more than two conventional rehabilitations and CAM, at the time of the interview.
      A total of 249 (48%) children reported lifetime CAM use, 23% used CAM at the time
      of the interview, and 62% of the patients planned to use CAM therapy in the
      future. Conventional rehabilitation therapies used at the time of the interview
      included physical therapy (30%), speech therapy (28%), and occupational therapy
      (19%), and the CAM therapies included herbal medicine (5%) and acupuncture or
      moxibustion (3%). The respondents indicated that in the future they planned to
      use acupuncture or moxibustion (57%), occupational therapy (18%), cognitive
      behavioral therapy (16%), speech therapy (10%), and physical therapy (8%).
      Conclusion. Concurrent management as conventional rehabilitations and CAM
      therapies is widely used by children with DDs. 

PMID- 24324521
TI  - Lectin from Crataeva tapia Bark Improves Tissue Damages and Plasma Hyperglycemia
      in Alloxan-Induced Diabetic Mice.
AB  - Crataeva tapia is a plant popularly used for diabetes treatment, in Brazil.
      Progressive decline in renal and hepatic functions has been described in patients
      with diabetes mellitus, and mortality rate is increased in patients with chronic
      liver and renal disease. This study aimed to evaluate whether Crataeva tapia bark
      lectin (CrataBL) improves hyperglycemia and renal and hepatic damage in diabetic
      mice. CrataBL was purified by ion exchange chromatography on CM-cellulose, and
      intraperitoneal administration of CrataBL to alloxan-induced diabetic mice at
      dose of 10 mg/Kg/day and 20 mg/Kg/day for 10 days significantly reduced serum
      glucose levels by 14.9% and 55.9%, respectively. Serum urea, creatinine,
      aspartate aminotransferase, and alanine aminotransferase were also significantly
      reduced after treatment with both doses of CrataBL. Furthermore, histological
      analysis of liver, kidney, and pancreas revealed an improvement in the tissue
      morphology upon treatment with CrataBL. The results suggest that CrataBL has a
      beneficial hypoglycemic activity and improves the renal and hepatic complications
      of diabetes. Therefore, this lectin may be a promising agent for the treatment of
      diabetes, and this might be the basis for its use in the folk medicine as an
      alternative treatment to manage diabetes-related complications such as
      hyperglycemia and tissue damage. 

PMID- 24324520
TI  - Relationship between Platelet PPARs, cAMP Levels, and P-Selectin Expression:
      Antiplatelet Activity of Natural Products.
AB  - Platelets are no longer considered simply as cells participating in thrombosis.
      In atherosclerosis, platelets are regulators of multiple processes, with the
      recruitment of inflammatory cells towards the lesion sites, inflammatory
      mediators release, and regulation of endothelial function. The antiplatelet
      therapy has been used for a long time in an effort to prevent and treat
      cardiovascular diseases. However, limited efficacy in some patients, drug
      resistance, and side effects are limitations of current antiplatelet therapy. In
      this context, a large number of natural products (polyphenols, terpenoids,
      alkaloids, and fatty acids) have been reported with antiplatelet activity. In
      this sense, the present paper describes mechanisms of antiplatelet action of
      natural products on platelet P-selectin expression through cAMP levels and its
      role as peroxisome proliferator-activated receptors agonists. 

PMID- 24324522
TI  - Continuous auricular electroacupuncture can significantly improve heart rate
      variability and clinical scores in patients with depression: first results from a
      transcontinental study.
AB  - The goal of this study was to investigate the impact and acceptability of
      providing continuous auricular electroacupuncture as an adjunct to conventional
      medications for patients with depression. Ten patients with a mean age +/- SD of
      43.3 +/- 10.4 years were able to provide informed consent. The quantitative and
      qualitative outcome measures were heart rate, heart rate variability (HRV), and
      different clinical scores. The study documented that a special kind of auricular
      electro acupuncture, applied over a period of three days, can improve various
      aspects of quality of life significantly but also highlighted the significant
      increase of HRV whilst having acupuncture treatment. In conclusion, our study
      shows stimulation-related and quantifiable clinical and physiological alterations
      in parameters after continuous auricular acupoint stimulation in patients with
      depression. Improved access to electro acupuncture treatment would be of major
      benefit for these patients. Further studies are necessary in order to verify the
      gained results. 

PMID- 24324523
TI  - A probabilistic approach for breast boundary extraction in mammograms.
AB  - The extraction of the breast boundary is crucial to perform further analysis of
      mammogram. Methods to extract the breast boundary can be classified into two
      categories: methods based on image processing techniques and those based on
      models. The former use image transformation techniques such as thresholding,
      morphological operations, and region growing. In the second category, the
      boundary is extracted using more advanced techniques, such as the active contour
      model. The problem with thresholding methods is that it is a hard to
      automatically find the optimal threshold value by using histogram information. On
      the other hand, active contour models require defining a starting point close to
      the actual boundary to be able to successfully extract the boundary. In this
      paper, we propose a probabilistic approach to address the aforementioned
      problems. In our approach we use local binary patterns to describe the texture
      around each pixel. In addition, the smoothness of the boundary is handled by
      using a new probability model. Experimental results show that the proposed method
      reaches 38% and 50% improvement with respect to the results obtained by the
      active contour model and threshold-based methods respectively, and it increases
      the stability of the boundary extraction process up to 86%. 

PMID- 24324524
TI  - A region growing vessel segmentation algorithm based on spectrum information.
AB  - We propose a region growing vessel segmentation algorithm based on spectrum
      information. First, the algorithm does Fourier transform on the region of
      interest containing vascular structures to obtain its spectrum information,
      according to which its primary feature direction will be extracted. Then combined
      edge information with primary feature direction computes the vascular structure's
      center points as the seed points of region growing segmentation. At last, the
      improved region growing method with branch-based growth strategy is used to
      segment the vessels. To prove the effectiveness of our algorithm, we use the
      retinal and abdomen liver vascular CT images to do experiments. The results show
      that the proposed vessel segmentation algorithm can not only extract the high
      quality target vessel region, but also can effectively reduce the manual
      intervention. 

PMID- 24324525
TI  - Contribution to the determination of in vivo mechanical characteristics of human
      skin by indentation test.
AB  - This paper proposes a triphasic model of intact skin in vivo based on a general
      phenomenological thermohydromechanical and physicochemical (THMPC) approach of
      heterogeneous media. The skin is seen here as a deforming stratified medium
      composed of four layers and made out of different fluid-saturated materials which
      contain also an ionic component. All the layers are treated as linear, isotropic
      materials described by their own behaviour law. The numerical simulations of in
      vivo indentation test performed on human skin are given. The numerical results
      correlate reasonably well with the typical observations of indented human skin.
      The discussion shows the versatility of this approach to obtain a better
      understanding on the mechanical behaviour of human skin layers separately. 

PMID- 24324526
TI  - Nonrigid registration of lung CT images based on tissue features.
AB  - Nonrigid image registration is a prerequisite for various medical image process
      and analysis applications. Much effort has been devoted to thoracic image
      registration due to breathing motion. Recently, scale-invariant feature transform
      (SIFT) has been used in medical image registration and obtained promising
      results. However, SIFT is apt to detect blob features. Blobs key points are
      generally detected in smooth areas which may contain few diagnostic points. In
      general, diagnostic points used in medical image are often vessel crossing
      points, vascular endpoints, and tissue boundary points, which provide abundant
      information about vessels and can reflect the motion of lungs accurately. These
      points generally have high gradients as opposed to blob key points and can be
      detected by Harris. In this work, we proposed a hybrid feature detection method
      which can detect tissue features of lungs effectively based on Harris and SIFT.
      In addition, a novel method which can remove mismatched landmarks is also
      proposed. A series of thoracic CT images are tested by using the proposed
      algorithm, and the quantitative and qualitative evaluations show that our method
      is statistically significantly better than conventional SIFT method especially in
      the case of large deformation of lungs during respiration. 

PMID- 24324527
TI  - Transcriptional protein-protein cooperativity in POU/HMG/DNA complexes revealed
      by normal mode analysis.
AB  - Biomolecular cooperativity is of great scientific interest due to its role in
      biological processes. Two transcription factors (TFs), Oct-4 and Sox-2, are
      crucial in transcriptional regulation of embryonic stem cells. In this paper, we
      analyze how Oct-1 (a similar POU factor) and Sox-2, interact cooperatively at
      their enhancer binding sites in collective motions. Normal mode analysis (NMA) is
      implemented to study the collective motions of two complexes with each involving
      these TFs and an enhancer. The special structure of Oct proteins is analyzed
      comprehensively, after which each Oct/Sox group is reassembled into two protein
      pairs. We subsequently propose a segmentation idea to extract the most correlated
      segments in each pair, using correlations of motion magnitude curves. The median
      analysis on these correlation values shows the intimacy of subunit POUS (Oct-1)
      and Sox-2. Using those larger-than-median correlation values, we conduct
      statistical studies and propose several protein-protein cooperative modes (S and
      D) coupled with their subtypes. Additional filters are applied and similar
      results are obtained. A supplementary study on the rotation angle curves reaches
      an agreement with these modes. Overall, these proposed cooperative modes provide
      useful information for us to understand the complicated interaction mechanism in
      the POU/HMG/DNA complexes. 

PMID- 24324528
TI  - Mindfulness for teachers: A pilot study to assess effects on stress, burnout and
      teaching efficacy.
AB  - Despite the crucial role of teachers in fostering children's academic learning
      and social-emotional well-being, addressing teacher stress in the classroom
      remains a significant challenge in education. The present study reports results
      from a randomized controlled pilot trial of a modified Mindfulness-Based Stress
      Reduction course (mMBSR) adapted specifically for teachers. Results suggest the
      course may be a promising intervention, with participants showing significant
      reductions in psychological symptoms and burnout, improvements in observer-rated
      classroom organization and performance on a computer task of affective
      attentional bias, and increases in self-compassion. In contrast, control group
      participants showed declines in cortisol functioning over time and marginally
      significant increases in burnout. Furthermore, changes in mindfulness were
      correlated in the expected direction with changes across several outcomes
      (psychological symptoms, burnout, sustained attention) in the intervention group.
      Implications of these findings for the training and support of teachers are
      discussed.

PMID- 24324529
TI  - One for the road! A study to assess the efficacy of single low-dose regimen of
      rasburicase in controlling hyperuricaemia in patients with tumour lysis syndrome
      due to haematological malignancies.
AB  - We conducted a retrospective audit of six patients with various haematological
      malignancies (two acute lymphoblastic leukaemia, one acute myeloid leukaemia, and
      three non-Hodgkin lymphoma); these patients were eligible to receive rasburicase,
      being at high risk of development of tumour lysis syndrome (TLS). They received a
      fixed single low-dose regimen of rasburicase (7.5 mg) mainly due to financial
      restriction, as patients were not supported by the National Health Service and
      did not have health insurance. We compared uric acid, creatinine levels, and
      electrolytes (i.e. phosphate, potassium, and calcium) before and after
      rasburicase administration and also assessed the need for renal replacement
      therapy after treatment. All six patients had a significant reduction in uric
      acid levels on the first day, achieving a response rate of 100% (p = 0.008994);
      creatinine, phosphate, and potassium were reduced significantly as well, with the
      p values of 0.0439, 0.014326, and 0.002008, respectively; only one patient needed
      renal replacement therapy in the form of haemodialysis, due to concerns about
      hyperphosphataemia. Financial difficulties faced either because patients lacked
      insurance or because of the restricted National Health Service budget in Egypt
      have resulted in the unavailability of certain modalities of treatment in cancer
      care and the need to consider more economic yet efficient approaches. Our
      experience suggests that a single low-dose rasburicase injection (7.5 mg) is an
      efficient and cost-effective method to control hyperuricaemia in patients with a
      high risk of developing TLS when compared with the more expensive and extended
      standard regimen and doses recommended. 

PMID- 24324531
TI  - Reductive surface synthesis of gold nanoparticles on silicate glass and their
      biochemical sensor applications.
AB  - Gold nanoparticles (Au NPs) were directly synthesized on the surface of
      polyvinylsilazane (PVSZ, -[(vinyl)SiH-NH2]-) without use of extra reductive
      additives. The reductive Si-H functional groups on the surface of cured PVSZ
      acted as surface bound reducing agents to form gold metal when contacted with an
      aqueous Au precursor (HAuCl4) solution, leading to formation of Au NPs adhered to
      silicate glass surface. The Au NPs-silicate platforms were preliminarily tested
      to detect Rhodamine B (1 MUM) by surface enhanced Raman scattering. Furthermore,
      gold microelectrode obtained by post-chemical plating was used as an integrated
      amperometric detection element in the polydimethylsilane-glass hybrid
      microfluidic chip. 

PMID- 24324530
TI  - Supraceliac and Infrarenal Aortic Flow in Patients with Abdominal Aortic
      Aneurysms: Mean Flows, Waveforms, and Allometric Scaling Relationships.
AB  - PURPOSE: Hemodynamic forces are thought to play a critical role in abdominal
      aortic aneurysm (AAA) growth. In silico and in vitro simulations can be used to
      study these forces, but require accurate aortic geometries and boundary
      conditions. Many AAA simulations use patient-specific geometries, but utilize
      inlet boundary conditions taken from a single, unrelated, healthy young adult.
      METHODS: In this study, we imaged 43 AAA patients using a 1.5 T MR scanner. A 24
      frame cardiac-gated one-component phase-contrast magnetic resonance imaging
      sequence was used to measure volumetric flow at the supraceliac (SC) and
      infrarenal (IR) aorta, where flow information is typically needed for simulation.
      For the first 36 patients, individual waveforms were interpolated to a 12-mode
      Fourier curve, peak-aligned, and averaged. Allometric scaling equations were
      derived from log-log plots of mean SC and IR flow vs. body mass, height, body
      surface area (BSA), and fat-free body mass. The data from the last seven patients
      were used to validate our model. RESULTS: Both the SC and IR averaged waveforms
      had the biphasic shapes characteristic of older adults, and mean SC and IR flows
      over the cardiac cycle were 51.2 +/- 10.3 and 17.5 +/- 5.44 mL/s, respectively.
      Linear regression of the log-log plots revealed that BSA was most strongly
      predictive of mean SC (R2 = 0.29) and IR flow (R2 = 0.19), with the highest
      combined R2. When averaged, the measured and predicted waveforms for the last
      seven patients agreed well. CONCLUSIONS: We present a method to estimate SC and
      IR mean flows and waveforms for AAA simulation.

PMID- 24324532
TI  - Experimental characterisation of a novel viscoelastic rectifier design.
AB  - A planar microfluidic system with contractions and obstacles is characterized in
      terms of anisotropic flow resistance due to viscoelastic effects. The working
      mechanism is illustrated using streak photography, while the diodicity
      performance is quantified by pressure drop measurements. The point of maximum
      performance is found to occur at relatively low elasticity levels, with diodicity
      around 3.5. Based on a previously published numerical work [Ejlebjerg et al.,
      Appl. Phys. Lett. 100, 234102 (2012)], 2D simulations of the FENE-CR differential
      constitutive model are also presented, but limited reproducibility and
      uncertainties of the experimental data prevent a direct comparison at low
      elasticity, where the flow is essentially two-dimensional. 

PMID- 24324540
TI  - All that glitters isn't gold: a survey on acknowledgment of limitations in
      biomedical studies.
AB  - BACKGROUND: Acknowledgment of all serious limitations to research evidence is
      important for patient care and scientific progress. Formal research on how
      biomedical authors acknowledge limitations is scarce. OBJECTIVES: To assess the
      extent to which limitations are acknowledged in biomedical publications
      explicitly, and implicitly by investigating the use of phrases that express
      uncertainty, so-called hedges; to assess the association between industry support
      and the extent of hedging. DESIGN: We analyzed reporting of limitations and use
      of hedges in 300 biomedical publications published in 30 high and medium -ranked
      journals in 2007. Hedges were assessed using linguistic software that assigned
      weights between 1 and 5 to each expression of uncertainty. RESULTS: Twenty-seven
      percent of publications (81/300) did not mention any limitations, while 73%
      acknowledged a median of 3 (range 1-8) limitations. Five percent mentioned a
      limitation in the abstract. After controlling for confounders, publications on
      industry-supported studies used significantly fewer hedges than publications not
      so supported (p = 0.028). LIMITATIONS: Detection and classification of
      limitations was--to some extent--subjective. The weighting scheme used by the
      hedging detection software has subjective elements. CONCLUSIONS: Reporting of
      limitations in biomedical publications is probably very incomplete. Transparent
      reporting of limitations may protect clinicians and guideline committees against
      overly confident beliefs and decisions and support scientific progress through
      better design, conduct or analysis of new studies.

PMID- 24324541
TI  - Linking reproduction and survival can improve model estimates of vital rates
      derived from limited time-series counts of pinnipeds and other species.
AB  - We propose a method to model the physiological link between somatic survival and
      reproductive output that reduces the number of parameters that need to be
      estimated by models designed to determine combinations of birth and death rates
      that produce historic counts of animal populations. We applied our Reproduction
      and Somatic Survival Linked (RSSL) method to the population counts of three
      species of North Pacific pinnipeds (harbor seals, Phoca vitulina richardii (Gray,
      1864); northern fur seals, Callorhinus ursinus (L., 1758); and Steller sea lions,
      Eumetopias jubatus (Schreber, 1776))--and found our model outperformed
      traditional models when fitting vital rates to common types of limited datasets,
      such as those from counts of pups and adults. However, our model did not perform
      as well when these basic counts of animals were augmented with additional
      observations of ratios of juveniles to total non-pups. In this case, the failure
      of the ratios to improve model performance may indicate that the relationship
      between survival and reproduction is redefined or disassociated as populations
      change over time or that the ratio of juveniles to total non-pups is not a
      meaningful index of vital rates. Overall, our RSSL models show advantages to
      linking survival and reproduction within models to estimate the vital rates of
      pinnipeds and other species that have limited time-series of counts.

PMID- 24324542
TI  - Dengue vector dynamics (Aedes aegypti) influenced by climate and social factors
      in Ecuador: implications for targeted control.
AB  - BACKGROUND: Dengue fever, a mosquito-borne viral disease, is now the fastest
      spreading tropical disease globally. Previous studies indicate that climate and
      human behavior interact to influence dengue virus and vector (Aedes aegypti)
      population dynamics; however, the relative effects of these variables depends on
      local ecology and social context. We investigated the roles of climate and socio
      ecological factors on Ae. aegypti population dynamics in Machala, a city in
      southern coastal Ecuador where dengue is hyper-endemic. METHODS/PRINCIPAL
      FINDINGS: We studied two proximate urban localities where we monitored weekly Ae.
      aegypti oviposition activity (Nov. 2010-June 2011), conducted seasonal pupal
      surveys, and surveyed household to identify dengue risk factors. The results of
      this study provide evidence that Ae. aegypti population dynamics are influenced
      by social risk factors that vary by season and lagged climate variables that vary
      by locality. Best-fit models to predict the presence of Ae. aegypti pupae
      included parameters for household water storage practices, access to piped water,
      the number of households per property, condition of the house and patio, and
      knowledge and perceptions of dengue. Rainfall and minimum temperature were
      significant predictors of oviposition activity, although the effect of rainfall
      varied by locality due to differences in types of water storage containers.
      CONCLUSIONS: These results indicate the potential to reduce the burden of dengue
      in this region by conducting focused vector control interventions that target
      high-risk households and containers in each season and by developing predictive
      models using climate and non-climate information. These findings provide the
      region's public health sector with key information for conducting time and
      location-specific vector control campaigns, and highlight the importance of local
      socio-ecological studies to understand dengue dynamics. See Text S1 for an
      executive summary in Spanish.

PMID- 24324543
TI  - Prospective multicenter study of community-associated skin and skin structure
      infections due to methicillin-resistant Staphylococcus aureus in Buenos Aires,
      Argentina.
AB  - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) is now the most common cause of skin and skin structure infections (SSSI)
      in several world regions. In Argentina prospective, multicenter clinical studies
      have only been conducted in pediatric populations. OBJECTIVE: PRIMARY: describe
      the prevalence, clinical and demographic characteristics of adult patients with
      community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA
      strains. Patients with MRSA were compared to those without MRSA. MATERIALS AND
      METHODS: Prospective, observational, multicenter, epidemiologic study, with
      molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires)
      between March 2010 and October 2011. Patients were included if they were >= 14
      years, were diagnosed with SSSI, a culture was obtained, and there had no
      significant healthcare contact identified. A logistic regression model was used
      to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL
      status were also determined. RESULTS: A total of 311 patients were included. CA
      MRSA was isolated in 70% (218/311) of patients. Clinical variables independently
      associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67,
      6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA
      strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The
      sequence type CA-MRSA ST30 spa t019 was the predominant clone. CONCLUSIONS: CA
      MRSA is now the most common cause of SSSI in our adult patients without
      healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in
      Buenos Aires, Argentina.

PMID- 24324545
TI  - Construction and characterization of highly infectious full-length molecular
      clones of a HIV-1 CRF07_BC isolate from Xinjiang, China.
AB  - Among the various subtypes of the M group of human immunodeficiency virus type 1
      (HIV-1), clade CRF07_BC is the most prevalent in China. To date, no strong
      replicable CRF07_BC infectious clone has been constructed. Here we report on the
      construction and characterization of highly replicable infectious molecular
      clones from the isolate XJDC6291 of this HIV-1 subtype. Four full-length clones
      pXJDC2-7, pXJDC3-7, pXJDC2-6 and pXJDC3-6 were successfully produced, but only
      pXJDC2-7 presented detectable infectivity and replication capability. To improve
      the replication capability of pXJDC2-7, a 4.8 kb region spanning from the pol
      Integrase to nef gene of the clone was replaced by PCR products of the
      corresponding fragments from the original isolate XJDC6291, which produced two
      clones pXJDC13 and pXJDC17 that exhibited strong replication capability. The
      viral stocks obtained by pXJDC-13 and pXJDC-17 transfection into 293T cells
      replicated efficiently in human PBMCs, human primary CD4(+) T cells and displayed
      CCR5 tropism. Sequence alignment between pXJDC13, pXJDC17 and pXJDC2-7 suggested
      that polymorphisms in the V1V2 region may influence infectivity, and reverse
      genetic experiment showed that V1V2 polymorphisms may influence the infectivity
      of the clones but did not affect the replication capability at a significant
      level. pXJDC13 and pXJDC17 displayed strong replication capability and are the
      first full-length infectious clones of HIV-1 CRF07_BC clade in the world. The
      availability of CRF07_BC infectious clones provides a useful tool for a wide
      range of studies, including antiretroviral drug and vaccine research as related
      to this HIV subtype. 

PMID- 24324544
TI  - Spontaneous NF-kappaB activation by autocrine TNFalpha signaling: a computational
      analysis.
AB  - NF-kappaB is a key transcription factor that regulates innate immune response.
      Its activity is tightly controlled by numerous feedback loops, including two
      negative loops mediated by NF-kappaB inducible inhibitors, IkappaBalpha and A20,
      which assure oscillatory responses, and by positive feedback loops arising due to
      the paracrine and autocrine regulation via TNFalpha, IL-1 and other cytokines. We
      study the NF-kappaB system of interlinked negative and positive feedback loops,
      combining bifurcation analysis of the deterministic approximation with stochastic
      numerical modeling. Positive feedback assures the existence of limit cycle
      oscillations in unstimulated wild-type cells and introduces bistability in A20
      deficient cells. We demonstrated that cells of significant autocrine potential,
      i.e., cells characterized by high secretion of TNFalpha and its receptor TNFR1,
      may exhibit sustained cytoplasmic-nuclear NF-kappaB oscillations which start
      spontaneously due to stochastic fluctuations. In A20-deficient cells even a small
      TNFalpha expression rate qualitatively influences system kinetics, leading to
      long-lasting NF-kappaB activation in response to a short-pulsed TNFalpha
      stimulation. As a consequence, cells with impaired A20 expression or increased
      TNFalpha secretion rate are expected to have elevated NF-kappaB activity even in
      the absence of stimulation. This may lead to chronic inflammation and promote
      cancer due to the persistent activation of antiapoptotic genes induced by NF
      kappaB. There is growing evidence that A20 mutations correlate with several types
      of lymphomas and elevated TNFalpha secretion is characteristic of many cancers.
      Interestingly, A20 loss or dysfunction also leaves the organism vulnerable to
      septic shock and massive apoptosis triggered by the uncontrolled TNFalpha
      secretion, which at high levels overcomes the antiapoptotic action of NF-kappaB.
      It is thus tempting to speculate that some cancers of deregulated NF-kappaB
      signaling may be prone to the pathogen-induced apoptosis. 

PMID- 24324546
TI  - Systematic construction of kinetic models from genome-scale metabolic networks.
AB  - The quantitative effects of environmental and genetic perturbations on metabolism
      can be studied in silico using kinetic models. We present a strategy for large
      scale model construction based on a logical layering of data such as reaction
      fluxes, metabolite concentrations, and kinetic constants. The resulting models
      contain realistic standard rate laws and plausible parameters, adhere to the laws
      of thermodynamics, and reproduce a predefined steady state. These features have
      not been simultaneously achieved by previous workflows. We demonstrate the
      advantages and limitations of the workflow by translating the yeast consensus
      metabolic network into a kinetic model. Despite crudely selected data, the model
      shows realistic control behaviour, a stable dynamic, and realistic response to
      perturbations in extracellular glucose concentrations. The paper concludes by
      outlining how new data can continuously be fed into the workflow and how
      iterative model building can assist in directing experiments. 

PMID- 24324547
TI  - Moving into protected areas? Setting conservation priorities for Romanian
      reptiles and amphibians at risk from climate change.
AB  - Rapid climate change represents one of the top threats to biodiversity, causing
      declines and extinctions of many species. Range shifts are a key response, but in
      many cases are incompatible with the current extent of protected areas. In this
      study we used ensemble species distribution models to identify range changes for
      21 reptile and 16 amphibian species in Romania for the 2020s and 2050s time
      horizons under three emission scenarios (A1B = integrated world, rapid economic
      growth, A2A = divided world, rapid economic growth [realistic scenario], B2A =
      regional development, environmentally-friendly scenario) and no- and limited
      dispersal assumptions. We then used irreplaceability analysis to test the
      efficacy of the Natura 2000 network to meet conservation targets. Under all
      scenarios and time horizons, 90% of the species suffered range contractions
      (greatest loses under scenarios B2A for 2020s, and A1B for 2050s), and four
      reptile species expanded their ranges. Two reptile and two amphibian species are
      predicted to completely lose climate space by 2050s. Currently, 35 species do not
      meet conservation targets (>40% representation in protected areas), but the
      target is predicted to be met for 4 - 14 species under future climate conditions,
      with higher representation under the limited-dispersal scenario. The Alpine and
      Steppic-Black Sea biogeographic regions have the highest irreplaceability value,
      and act as climate refugia for many reptiles and amphibians. The Natura 2000
      network performs better for achieving herpetofauna conservation goals in the
      future, owing to the interaction between drastic range contractions, and range
      shifts towards existing protected areas. Thus, conservation actions for
      herpetofauna in Romania need to focus on: (1) building institutional capacity of
      protected areas in the Alpine and Steppic-Black Sea biogeographic regions, and
      (2) facilitating natural range shifts by improving the conservation status of
      herpetofauna outside protected areas, specifically in traditionally-managed
      landscapes and abandoned cropland. 

PMID- 24324548
TI  - Overexpression of multiple detoxification genes in deltamethrin resistant
      Laodelphax striatellus (Hemiptera: Delphacidae) in China.
AB  - BACKGROUND: The small brown planthopper (SBPH), Laodelphax striatellus (Fallen),
      is one of the major rice pests in Asia and has developed resistance to multiple
      classes of insecticides. Understanding resistance mechanisms is essential to the
      management of this pest. Biochemical and molecular assays were performed in this
      study to systematically characterize deltamethrin resistance mechanisms with
      laboratory-selected resistant and susceptible strains of SBPH.
      METHODOLOGY/PRINCIPAL FINDINGS: Deltamethrin resistant strains of SBPH (JH-del)
      were derived from a field population by continuously selections (up to 30
      generations) in the laboratory, while a susceptible strain (JHS) was obtained
      from the same population by removing insecticide pressure for 30 generations. The
      role of detoxification enzymes in the resistance was investigated using synergism
      and enzyme activity assays with strains of different resistant levels.
      Furthermore, 71 cytochrome P450, 93 esterases and 12 glutathione-S-transferases
      cDNAs were cloned based on transcriptome data of a field collected population.
      Semi-quantitative RT-PCR screening analysis of 176 identified detoxification
      genes demonstrated that multiple P450 and esterase genes were overexpressed (>2
      fold) in JH-del strains (G4 and G30) when compared to that in JHS, and the
      results of quantitative PCR coincided with the semi-quantitative RT-PCR results.
      Target mutation at IIS3-IIS6 regions encoded by the voltage-gated sodium channel
      gene was ruled out for conferring the observed resistance.
      CONCLUSION/SIGNIFICANCE: As the first attempt to discover genes potentially
      involved in SBPH pyrethroid resistance, this study putatively identified several
      candidate genes of detoxification enzymes that were significantly overexpressed
      in the resistant strain, which matched the synergism and enzyme activity testing.
      The biochemical and molecular evidences suggest that the high level pyrethroid
      resistance in L. striatellus could be due to enhanced detoxification rather than
      target insensitivity. The findings lay a solid ground for further resistance
      mechanism elucidation studies.

PMID- 24324549
TI  - SEL1L regulates adhesion, proliferation and secretion of insulin by affecting
      integrin signaling.
AB  - SEL1L, a component of the endoplasmic reticulum associated degradation (ERAD)
      pathway, has been reported to regulate the (i) differentiation of the pancreatic
      endocrine and exocrine tissue during the second transition of mouse embryonic
      development, (ii) neural stem cell self-renewal and lineage commitment and (iii)
      cell cycle progression through regulation of genes related to cell-matrix
      interaction. Here we show that in the pancreas the expression of SEL1L is
      developmentally regulated, such that it is readily detected in developing islet
      cells and in nascent acinar clusters adjacent to basement membranes, and becomes
      progressively restricted to the islets of Langherans in post-natal life. This
      peculiar expression pattern and the presence of two inverse RGD motifs in the
      fibronectin type II domain of SEL1L protein indicate a possible interaction with
      cell adhesion molecules to regulate islets architecture. Co-immunoprecipitation
      studies revealed SEL1L and beta1-integrin interaction and, down-modulation of
      SEL1L in pancreatic beta-cells, negatively influences both cell adhesion on
      selected matrix components and cell proliferation likely due to altered ERK
      signaling. Furthermore, the absence of SEL1L protein strongly inhibits glucose
      stimulated insulin secretion in isolated mouse pancreatic islets unveiling an
      important role of SEL1L in insulin trafficking. This phenotype can be rescued by
      the ectopic expression of the beta1-integrin subunit confirming the close
      interaction of these two proteins in regulating the cross-talk between
      extracellular matrix and insulin signalling to create a favourable micro
      environment for beta-cell development and function. 

PMID- 24324550
TI  - A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane
      resistant cells.
AB  - Microtubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and
      vinca alkaloids have been successfully used in the clinic over the past thirty
      years against a broad range of tumors. However, two factors have limited the
      effectiveness of microtubule inhibitors: toxicity and resistance. In particular,
      the latter is highly unpredictable, variable from patient to patient and is
      believed to be the cause of treatment failure in most cases of metastatic
      cancers. For these reasons, there is an increasing demand for new microtubule
      inhibitors that can overcome resistance mechanisms and that, at the same time,
      have reduced side effects. Here we present a novel microtubule inhibitor, 4SC
      207, which shows strong anti-proliferative activity in a large panel of tumor
      cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in
      multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a
      poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in
      vitro and in vivo and promotes, in a dose dependent manner, a mitotic
      delay/arrest, followed by apoptosis or aberrant divisions due to chromosome
      alignment defects and formation of multi-polar spindles. Furthermore, preliminary
      data from preclinical studies suggest low propensity towards bone marrow
      toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant
      xenograft models. In summary, our results suggest that 4SC-207 may be a potential
      anti-cancer agent.

PMID- 24324551
TI  - Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma
      cruzi seropositive subjects.
AB  - BACKGROUND: Familial aggregation of Chagas cardiac disease in T. cruzi-infected
      persons suggests that human genetic variation may be an important determinant of
      disease progression. OBJECTIVE: To perform a GWAS using a well-characterized
      cohort to detect single nucleotide polymorphisms (SNPs) and genes associated with
      cardiac outcomes. METHODS: A retrospective cohort study was developed by the
      NHLBI REDS-II program in Brazil. Samples were collected from 499 T. cruzi
      seropositive blood donors who had donated between 1996 and 2002, and 101 patients
      with clinically diagnosed Chagas cardiomyopathy. In 2008-2010, all subjects
      underwent a complete medical examination. After genotype calling, quality control
      filtering with exclusion of 20 cases, and imputation of 1,000 genomes variants;
      association analysis was performed for 7 cardiac and parasite related traits,
      adjusting for population stratification. RESULTS: The cohort showed a wide range
      of African, European, and modest Native American admixture proportions,
      consistent with the recent history of Brazil. No SNPs were found to be highly
      (P<10(-8)) associated with cardiomyopathy. The two mostly highly associated SNPs
      for cardiomyopathy (rs4149018 and rs12582717; P-values <10(-6)) are located on
      Chromosome 12p12.2 in the SLCO1B1 gene, a solute carrier family member. We
      identified 44 additional genic SNPs associated with six traits at P-value <10(
      6): Ejection Fraction, PR, QRS, QT intervals, antibody levels by EIA, and
      parasitemia by PCR. CONCLUSION: This GWAS identified suggestive SNPs that may
      impact the risk of progression to cardiomyopathy. Although this Chagas cohort is
      the largest examined by GWAS to date, (580 subjects), moderate sample size may
      explain in part the limited number of significant SNP variants. Enlarging the
      current sample through expanded cohorts and meta-analyses, and targeted studies
      of candidate genes, will be required to confirm and extend the results reported
      here. Future studies should also include exposed seronegative controls to
      investigate genetic associations with susceptibility or resistance to T. cruzi
      infection and non-Chagas cardiomyopathy.

PMID- 24324552
TI  - Computational prediction of human salivary proteins from blood circulation and
      application to diagnostic biomarker identification.
AB  - Proteins can move from blood circulation into salivary glands through active
      transportation, passive diffusion or ultrafiltration, some of which are then
      released into saliva and hence can potentially serve as biomarkers for diseases
      if accurately identified. We present a novel computational method for predicting
      salivary proteins that come from circulation. The basis for the prediction is a
      set of physiochemical and sequence features we found to be discerning between
      human proteins known to be movable from circulation to saliva and proteins deemed
      to be not in saliva. A classifier was trained based on these features using a
      support-vector machine to predict protein secretion into saliva. The classifier
      achieved 88.56% average recall and 90.76% average precision in 10-fold cross
      validation on the training data, indicating that the selected features are
      informative. Considering the possibility that our negative training data may not
      be highly reliable (i.e., proteins predicted to be not in saliva), we have also
      trained a ranking method, aiming to rank the known salivary proteins from
      circulation as the highest among the proteins in the general background, based on
      the same features. This prediction capability can be used to predict potential
      biomarker proteins for specific human diseases when coupled with the information
      of differentially expressed proteins in diseased versus healthy control tissues
      and a prediction capability for blood-secretory proteins. Using such integrated
      information, we predicted 31 candidate biomarker proteins in saliva for breast
      cancer. 

PMID- 24324553
TI  - Mapping the structural and dynamical features of multiple p53 DNA binding
      domains: insights into loop 1 intrinsic dynamics.
AB  - The transcription factor p53 regulates cellular integrity in response to stress.
      p53 is mutated in more than half of cancerous cells, with a majority of the
      mutations localized to the DNA binding domain (DBD). In order to map the
      structural and dynamical features of the DBD, we carried out multiple copy
      molecular dynamics simulations (totaling 0.8 MUs). Simulations show the loop 1 to
      be the most dynamic element among the DNA-contacting loops (loops 1-3). Loop 1
      occupies two major conformational states: extended and recessed; the former but
      not the latter displays correlations in atomic fluctuations with those of loop 2
      (~24 A apart). Since loop 1 binds to the major groove whereas loop 2 binds to the
      minor groove of DNA, our results begin to provide some insight into the possible
      mechanism underpinning the cooperative nature of DBD binding to DNA. We propose
      (1) a novel mechanism underlying the dynamics of loop 1 and the possible tread
      milling of p53 on DNA and (2) possible mutations on loop 1 residues to restore
      the transcriptional activity of an oncogenic mutation at a distant site. 

PMID- 24324554
TI  - Fact retrieval and memory consolidation for a movement sequence: bidirectional
      effects of 'unrelated' cognitive tasks on procedural memory.
AB  - The generation of long-term memory for motor skills can be modulated by
      subsequent motor experiences that interfere with the consolidation process.
      Recent studies suggest that even a non-motor task may adversely affect some
      aspects of motor sequence memory. Here we show that motor sequence memory can be
      either enhanced or reduced, by different cognitive tasks. Participants were
      trained in performing finger movement sequences. Fully explicit instructions
      about the target sequence were given before practice. The buildup of procedural
      knowledge was tested at three time-points: immediately before training (T1),
      after practice (T2), and 24 hours later (T3). Each participant performed the task
      on two separate occasions; training on a different movement sequence on each
      occasion. In one condition, interference, participants performed a non-motor task
      immediately after T2. Half the participants solved simple math problems and half
      performed a simple semantic judgment task. In the baseline condition there was no
      additional task. All participants improved significantly between T1 and T2
      (within-session gains). In addition, in the baseline condition, performance
      significantly improved between T2 and T3 (delayed 'off-line' gains). Solving math
      problems significantly enhanced these delayed gains in motor performance, whereas
      performing semantic decisions significantly reduced delayed gains compared to
      baseline. Thus, procedural motor memory consolidation can be either enhanced or
      inhibited by subsequent cognitive experiences. These effects do not require
      explicit or implicit new learning. The retrieval of unrelated, non-motor, well
      established knowledge can modulate procedural memory. 

PMID- 24324555
TI  - Helical carbon nanotubes enhance the early immune response and inhibit macrophage
      mediated phagocytosis of Pseudomonas aeruginosa.
AB  - Aerosolized or aspirated manufactured carbon nanotubes have been shown to be
      cytotoxic, cause pulmonary lesions, and demonstrate immunomodulatory properties.
      CD-1 mice were used to assess pulmonary toxicity of helical carbon nanotubes
      (HCNTs) and alterations of the immune response to subsequent infection by
      Pseudomonas aeruginosa in mice. HCNTs provoked a mild inflammatory response
      following either a single exposure or 2X/week for three weeks (multiple
      exposures) but were not significantly toxic. Administering HCNTs 2X/week for
      three weeks resulted in pulmonary lesions including granulomas and goblet cell
      hyperplasia. Mice exposed to HCNTs and subsequently infected by P. aeruginosa
      demonstrated an enhanced inflammatory response to P. aeruginosa and phagocytosis
      by alveolar macrophages was inhibited. However, clearance of P. aeruginosa was
      not affected. HCNT exposed mice depleted of neutrophils were more effective in
      clearing P. aeruginosa compared to neutrophil-depleted control mice, accompanied
      by an influx of macrophages. Depletion of systemic macrophages resulted in
      slightly inhibited bacterial clearance by HCNT treated mice. Our data indicate
      that pulmonary exposure to HCNTs results in lesions similar to those caused by
      other nanotubes and pre-exposure to HCNTs inhibit alveolar macrophage
      phagocytosis of P. aeruginosa. However, clearance was not affected as exposure to
      HCNTs primed the immune system for an enhanced inflammatory response to pulmonary
      infection consisting of an influx of neutrophils and macrophages. 

PMID- 24324556
TI  - Adiponectin receptor 2 deficiency results in reduced atherosclerosis in the
      brachiocephalic artery in apolipoprotein E deficient mice.
AB  - Adiponectin has been shown to have beneficial cardiovascular effects and to
      signal through the adiponectin receptors, AdipoR1 and AdipoR2. The original aim
      of this study was to investigate the effect of combined AdipoR1 and AdipoR2
      deficiency (AdipoR1(-/-)AdipoR2(-/-)) on atherosclerosis. However, we made the
      interesting observation that AdipoR1(-/-) AdipoR2(-/-) leads to embryonic
      lethality demonstrating the critical importance of the adiponectin signalling
      system during development. We then investigated the effect of AdipoR2-ablation on
      the progression of atherosclerosis in apolipoprotein E deficient (ApoE(-/-))
      mice. AdipoR2(-/-)ApoE(-/-) mice fed an atherogenic diet had decreased plaque
      area in the brachiocephalic artery compared with AdipoR2(+/+) ApoE(-/-)
      littermate controls as visualized in vivo using an ultrasound biomicroscope and
      confirmed by histological analyses. The decreased plaque area in the
      brachiocephalic artery could not be explained by plasma cholesterol levels or
      inflammatory status. However, accumulation of neutral lipids was decreased in
      peritoneal macrophages from AdipoR2(-/-)ApoE(-/-) mice after incubation with
      oxidized LDL. This effect was associated with lower CD36 and higher ABCA1 mRNA
      levels in peritoneal macrophages from AdipoR2(-/-)ApoE(-/-) mice compared with
      AdipoR2(+/+)ApoE(-/-) controls after incubation with oxidized LDL. In summary, we
      show that adiponectin receptors are crucial during embryonic development and that
      AdipoR2-deficiency slows down the progression of atherosclerosis in the
      brachiocephalic artery of ApoE-deficient mice.

PMID- 24324557
TI  - Canonical Wnt signaling promotes early hematopoietic progenitor formation and
      erythroid specification during embryonic stem cell differentiation.
AB  - The generation of hematopoietic stem cells (HSCs) during development is a complex
      process linked to morphogenic signals. Understanding this process is important
      for regenerative medicine applications that require in vitro production of HSC.
      In this study we investigated the effects of canonical Wnt/beta-catenin signaling
      during early embryonic differentiation and hematopoietic specification using an
      embryonic stem cell system. Our data clearly demonstrates that following early
      differentiation induction, canonical Wnt signaling induces a strong mesodermal
      program whilst maintaining a degree of stemness potential. This involved a
      complex interplay between beta-catenin/TCF/LEF/Brachyury/Nanog. beta-catenin
      mediated up-regulation of TCF/LEF resulted in enhanced brachyury levels, which in
      turn lead to Nanog up-regulation. During differentiation, active canonical Wnt
      signaling also up-regulated key transcription factors and cell specific markers
      essential for hematopoietic specification, in particular genes involved in
      establishing primitive erythropoiesis. This led to a significant increase in
      primitive erythroid colony formation. beta-catenin signaling also augmented early
      hematopoietic and multipotent progenitor (MPP) formation. Following culture in a
      MPP specific cytokine cocktail, activation of beta-catenin suppressed
      differentiation of the early hematopoietic progenitor population, with cells
      displaying a higher replating capacity and a propensity to form megakaryocytic
      erythroid progenitors. This bias towards erythroid lineage commitment was also
      observed when hematopoietic progenitors were directed to undergo myeloid colony
      formation. Overall this study underscores the importance of canonical Wnt/beta
      catenin signaling in mesodermal specification, primitive erythropoiesis and early
      hematopietic progenitor formation during hematopoietic induction. 

PMID- 24324558
TI  - Oxidative stress and regulation of Pink1 in zebrafish (Danio rerio).
AB  - Oxidative stress-mediated neuronal dysfunction is characteristic of several
      neurodegenerative disorders, including Parkinson's disease (PD). The enzyme
      tyrosine hydroxylase (TH) catalyzes the formation of L-DOPA, the rate-limiting
      step in the biosynthesis of dopamine. A lack of dopamine in the striatum is the
      most characteristic feature of PD, and the cause of the most dominant symptoms.
      Loss of function mutations in the PTEN-induced putative kinase (PINK1) gene cause
      autosomal recessive PD. This study explored the basic mechanisms underlying the
      involvement of pink1 in oxidative stress-mediated PD pathology using zebrafish as
      a tool. We generated a transgenic line, Tg(pink1:EGFP), and used it to study the
      effect of oxidative stress (exposure to H2O2) on pink1 expression. GFP expression
      was enhanced throughout the brain of zebrafish larvae subjected to oxidative
      stress. In addition to a widespread increase in pink1 mRNA expression, mild
      oxidative stress induced a clear decline in tyrosine hydroxylase 2 (th2), but not
      tyrosine hydroxylase 1 (th1) expression, in the brain of wild-type larvae. The
      drug L-Glutathione Reduced (LGR) has been associated with anti-oxidative and
      possible neuroprotective properties. Administration of LGR normalized the
      increased fluorescence intensity indicating pink1 transgene expression and
      endogenous pink1 mRNA expression in larvae subjected to oxidative stress by H2O2.
      In the pink1 morpholino oliogonucleotide-injected larvae, the reduction in the
      expression of th1 and th2 was partially rescued by LGR. The pink1 gene is a
      sensitive marker of oxidative stress in zebrafish, and LGR effectively normalizes
      the consequences of mild oxidative stress, suggesting that the neuroprotective
      effects of pink1 and LGR may be significant and useful in drug development. 

PMID- 24324559
TI  - 3-D visualization and quantitation of microvessels in transparent human
      colorectal carcinoma [corrected].
AB  - Microscopic analysis of tumor vasculature plays an important role in
      understanding the progression and malignancy of colorectal carcinoma. However,
      due to the geometry of blood vessels and their connections, standard microtome
      based histology is limited in providing the spatial information of the vascular
      network with a 3-dimensional (3-D) continuum. To facilitate 3-D tissue analysis,
      we prepared transparent human colorectal biopsies by optical clearing for in
      depth confocal microscopy with CD34 immunohistochemistry. Full-depth colons were
      obtained from colectomies performed for colorectal carcinoma. Specimens were
      prepared away from (control) and at the tumor site. Taking advantage of the
      transparent specimens, we acquired anatomic information up to 200 MUm in depth
      for qualitative and quantitative analyses of the vasculature. Examples are given
      to illustrate: (1) the association between the tumor microstructure and
      vasculature in space, including the perivascular cuffs of tumor outgrowth, and
      (2) the difference between the 2-D and 3-D quantitation of microvessels. We also
      demonstrate that the optically cleared mucosa can be retrieved after 3-D
      microscopy to perform the standard microtome-based histology (H&E staining and
      immunohistochemistry) for systematic integration of the two tissue imaging
      methods. Overall, we established a new tumor histological approach to integrate 3
      D imaging, illustration, and quantitation of human colonic microvessels in normal
      and cancerous specimens. This approach has significant promise to work with the
      standard histology to better characterize the tumor microenvironment in
      colorectal carcinoma. 

PMID- 24324560
TI  - Binding mechanism and electrochemical properties of M13 phage-sulfur composite.
AB  - Self-assembly of nanostructured materials has been proven a powerful technique in
      material design and synthesis. By phage display screening, M13 phage was found to
      strongly bind sulfur particles. Fourier transform infrared and X-ray
      photoelectron spectroscopy measurements indicated that the strong sulfur-binding
      ability of M13 phage derives from newly generated S-O and C-S bonds. Using this
      phage assembled sulfur composite in a lithium battery, the first discharge
      capacity reached 1117 mAh g(-1), which is more than twice that of the sulfur only
      cathode. Besides, the negative polysulfide shuttle effect in a lithium-sulfur
      battery was significantly suppressed. 

PMID- 24324571
TI  - Associations between tumor necrosis factor-alpha polymorphisms and risk of
      psoriasis: a meta-analysis.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) may play an important role in
      the recalcitrant inflammatory and hyperproliferative dermatosis of psoriasis, and
      there may be a relationship between TNF-alpha polymorphisms and psoriasis risk.
      METHODS: We performed a meta-analysis to evaluate the associations between TNF
      alpha polymorphisms and psoriasis. Electronic searches of Pubmed, Embase, and Web
      of Science were performed for all publications on the associations between TNF
      alpha polymorphisms and psoriasis through September 26, 2012. The pooled odds
      ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to
      assess the associations. RESULTS: Sixteen case-control studies with a total of
      2,253 psoriasis cases and 1,947 controls on TNF-alpha 308 G/A polymorphism and
      fourteen studies on TNF-alpha 238 G/A polymorphism with 2,104 cases and 1,838
      controls were finally included into the meta-analysis. Overall, TNF-alpha 308 G/A
      polymorphism was significantly associated with decreased risk of psoriasis under
      three genetic comparison models (for A versus G: fixed-effects OR 0.71, 95%CI
      0.62-0.82, P < 0.001; for AG versus GG: fixed-effects OR 0.67, 95%CI 0.57-0.78, P
      < 0.001; for AA/AG versus GG: fixed-effects OR 0.67, 95%CI 0.58-0.78, P < 0.001).
      In addition, TNF-alpha 238 G/A polymorphism was associated with increased risk of
      psoriasis under three genetic models (for A versus G: fixed-effects OR 2.46,
      95%CI 2.04-2.96, P < 0.001; for AG versus GG: fixed-effects OR 2.69, 95%CI 2.20
      3.28, P < 0.001; for AA/AG versus GG: fixed-effects OR 2.68, 95%CI 2.20-3.26, P <
      0.001). Subgroup analysis by ethnicity identified a significant association
      between TNF-alpha 308 G/A polymorphism and decreased risk of psoriasis in both
      Caucasians and Asians and a significant association between TNF-alpha 238 G/A
      polymorphism and increased risk of psoriasis in Caucasians. CONCLUSIONS: The meta
      analysis suggests that TNF-alpha 308 G/A polymorphism is associated with
      decreased risk of psoriasis, while TNF-alpha 238 G/A is associated with increased
      risk of psoriasis.

PMID- 24324572
TI  - Using stable isotope compositions of animal tissues to infer trophic interactions
      in Gulf of Mexico lower slope seep communities.
AB  - We analyzed the tissue carbon, nitrogen, and sulfur stable isotope contents of
      macrofaunal communities associated with vestimentiferan tubeworms and
      bathymodiolin mussels from the Gulf of Mexico lower continental slope (970-2800
      m). Shrimp in the genus Alvinocaris associated with vestimentiferans from shallow
      (530 m) and deep (1400-2800 m) sites were used to test the hypothesis that seep
      animals derive a greater proportion of their nutrition from seeps (i.e. a lower
      proportion from the surface) at greater depths. To account for spatial
      variability in the inorganic source pool, we used the differences between the
      mean tissue delta(13)C and delta(15)N of the shrimp in each collection and the
      mean delta (13)C and delta(15)N values of the vestimentiferans from the same
      collection, since vestimentiferans are functionally autotrophic and serve as a
      baseline for environmental isotopic variation. There was a significant negative
      relationship between this difference and depth for both delta(13)C and delta(15)N
      (p=0.02 and 0.007, respectively), which supports the hypothesis of higher
      dependence on seep nutrition with depth. The small polychaete worm Protomystides
      sp. was hypothesized to be a blood parasite of the vestimentiferan
      Escarpialaminata. There was a highly significant linear relationship between the
      delta(13)C values of Protomystides sp. and the E. laminata individuals to which
      they were attached across all collections (p < 0.001) and within a single
      collection (p = 0.01), although this relationship was not significant for
      delta(15)N and delta(34)S. We made several other qualitative inferences with
      respect to the feeding biology of the taxa occurring in these lower slope seeps,
      some of which have not been described prior to this study. 

PMID- 24324573
TI  - Low prevalence of liver disease but regional differences in HBV treatment
      characteristics mark HIV/HBV co-infection in a South African HIV clinical trial.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is endemic in South Africa however,
      there is limited data on the degree of liver disease and geographic variation in
      HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA
      'Safeguard the household study' in order to assess baseline HBV characteristics
      in HIV/HBV co-infection participants prior to antiretroviral therapy (ART)
      initiation. METHODS: 812 participants from two South African townships Soweto and
      Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants
      were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen
      (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline. RESULTS: Forty
      eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of
      those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a
      FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV
      prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk
      2.3; 95% CI: 1.3-4.0). More participants in Masiphumelele had HBeAg-negative
      disease (58% vs. 12%, p = 0.002) and HBV DNA levels <=2000 IU/ml, (43% vs. 6%
      p<0.007). CONCLUSION: One third of HIV/HBV co-infected subjects had low HBV DNA
      levels and ALT while the majority had indicators of only mild liver disease.
      There were substantial regional differences in HBsAg and HbeAg prevalence in
      HIV/HBV co-infection between two regions in South Africa. This study highlights
      the absence of severe liver disease and the marked regional differences in
      HIV/HBV co-infection in South Africa and will inform treatment decisions in these
      populations.

PMID- 24324574
TI  - Impact of simulated microgravity on oligodendrocyte development: implications for
      central nervous system repair.
AB  - We have recently established a culture system to study the impact of simulated
      microgravity on oligodendrocyte progenitor cells (OPCs) development. We subjected
      mouse and human OPCs to a short exposure of simulated microgravity produced by a
      3D-Clinostat robot. Our results demonstrate that rodent and human OPCs display
      enhanced and sustained proliferation when exposed to simulated microgravity as
      assessed by several parameters, including a decrease in the cell cycle time.
      Additionally, OPC migration was examined in vitro using time-lapse imaging of
      cultured OPCs. Our results indicated that OPCs migrate to a greater extent after
      stimulated microgravity than in normal conditions, and this enhanced motility was
      associated with OPC morphological changes. The lack of normal gravity resulted in
      a significant increase in the migration speed of mouse and human OPCs and we
      found that the average leading process in migrating bipolar OPCs was
      significantly longer in microgravity treated cells than in controls,
      demonstrating that during OPC migration the lack of gravity promotes leading
      process extension, an essential step in the process of OPC migration. Finally, we
      tested the effect of simulated microgravity on OPC differentiation. Our data
      showed that the expression of mature oligodendrocyte markers was significantly
      delayed in microgravity treated OPCs. Under conditions where OPCs were allowed to
      progress in the lineage, simulated microgravity decreased the proportion of cells
      that expressed mature markers, such as CC1 and MBP, with a concomitant increased
      number of cells that retained immature oligodendrocyte markers such as Sox2 and
      NG2. Development of methodologies aimed at enhancing the number of OPCs and their
      ability to progress on the oligodendrocyte lineage is of great value for
      treatment of demyelinating disorders. To our knowledge, this is the first report
      on the gravitational modulation of oligodendrocyte intrinsic plasticity to
      increase their progenies. 

PMID- 24324575
TI  - Heat-stress and light-stress induce different cellular pathologies in the
      symbiotic dinoflagellate during coral bleaching.
AB  - Coral bleaching is a significant contributor to the worldwide degradation of
      coral reefs and is indicative of the termination of symbiosis between the coral
      host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually
      by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we
      provide evidence that during the earliest stages of environmentally induced
      bleaching, heat stress and light stress generate distinctly different
      pathomorphological changes in the chloroplasts, while a combined heat- and light
      stress exposure induces both pathomorphologies; suggesting that these stressors
      act on the dinoflagellate by different mechanisms. Within the first 48 hours of a
      heat stress (32 degrees C) under low-light conditions, heat stress induced
      decomposition of thylakoid structures before observation of extensive oxidative
      damage; thus it is the disorganization of the thylakoids that creates the
      conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours
      of a light stress (2007 umoles m(-2) s(-1) PAR) at 25 degrees C, condensation or
      fusion of multiple thylakoid lamellae occurred coincidently with levels of
      oxidative damage products, implying that photo-oxidative stress causes the
      structural membrane damage within the chloroplasts. Exposure to combined heat-
      and light-stresses induced both pathomorphologies, confirming that these
      stressors acted on the dinoflagellate via different mechanisms. Within 72 hours
      of exposure to heat and/or light stresses, homeostatic processes (e.g., heat
      shock protein and anti-oxidant enzyme response) were evident in the remaining
      intact dinoflagellates, regardless of the initiating stressor. Understanding the
      sequence of events during bleaching when triggered by different environmental
      stressors is important for predicting both severity and consequences of coral
      bleaching. 

PMID- 24324576
TI  - Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors:
      implications for the selection of CTL donor.
AB  - Adoptive transfer of antiviral T cells enhances immune reconstitution and
      decreases infectious complications after stem cell transplantation. Information
      on number and function of antiviral T cells in stem cell grafts is scarce. We
      investigated (1) immunomodulatory effects of G-CSF on antiviral T cells, (2) the
      influence of apheresis, and (3) the optimal time point to collect antiviral
      cells. CMV-, EBV- and ADV-specific T cells were enumerated in 170 G-CSF-mobilized
      stem cell and 24 non-mobilized platelet donors using 14 HLA-matched multimers. T
      cell function was evaluated by IFN-gamma ELISpot and granzyme B secretion.
      Immunophenotyping was performed by multicolor flow cytometry. G-CSF treatment did
      not significantly influence frequency of antiviral T cells nor their in vitro
      expansion rate upon antigen restimulation. However, T-cell function was
      significantly impaired, as expressed by a mean reduction in secretion of IFN
      gamma (75% in vivo, 40% in vitro) and granzyme B (32% target-independent, 76%
      target-dependent) as well as CD107a expression (27%). Clinical follow up data
      indicate that the first CMV-reactivation in patients and with it the need for T
      cell transfer occurs while the donor is still under the influence of G-CSF. To
      overcome these limitations, T-cell banking before mobilization or recruitment of
      third party donors might be an option to optimize T-cell production. 

PMID- 24324577
TI  - Bridging the gap between single molecule and ensemble methods for measuring
      lateral dynamics in the plasma membrane.
AB  - The lateral dynamics of proteins and lipids in the mammalian plasma membrane are
      heterogeneous likely reflecting both a complex molecular organization and
      interactions with other macromolecules that reside outside the plane of the
      membrane. Several methods are commonly used for characterizing the lateral
      dynamics of lipids and proteins. These experimental and data analysis methods
      differ in equipment requirements, labeling complexities, and further oftentimes
      give different results. It would therefore be very convenient to have a single
      method that is flexible in the choice of fluorescent label and labeling densities
      from single molecules to ensemble measurements, that can be performed on a
      conventional wide-field microscope, and that is suitable for fast and accurate
      analysis. In this work we show that k-space image correlation spectroscopy (kICS)
      analysis, a technique which was originally developed for analyzing lateral
      dynamics in samples that are labeled at high densities, can also be used for fast
      and accurate analysis of single molecule density data of lipids and proteins
      labeled with quantum dots (QDs). We have further used kICS to investigate the
      effect of the label size and by comparing the results for a biotinylated lipid
      labeled at high densities with Atto647N-strepatvidin (sAv) or sparse densities
      with sAv-QDs. In this latter case, we see that the recovered diffusion rate is
      two-fold greater for the same lipid and in the same cell-type when labeled with
      Atto647N-sAv as compared to sAv-QDs. This data demonstrates that kICS can be used
      for analysis of single molecule data and furthermore can bridge between samples
      with a labeling densities ranging from single molecule to ensemble level
      measurements. 

PMID- 24324578
TI  - The thyroid receptor modulator KB3495 reduces atherosclerosis independently of
      total cholesterol in the circulation in ApoE deficient mice.
AB  - BACKGROUND: Thyroid hormones (TH) regulate cholesterol metabolism but their use
      as lipid-lowering drugs is restricted due to negative cardiac effects. TH mimetic
      compounds modulating TH receptor beta (THRbeta) have been designed as potential
      drugs, reducing serum cholesterol levels while avoiding apparent deleterious
      cardiac effects. OBJECTIVE: Using ApoE deficient mice, we examined whether
      KB3495, a TH mimetic compound, reduces atherosclerosis and if there is a
      synergistic effect with atorvastatin. The effect of KB3495 was investigated after
      10 and 25 weeks. RESULTS: KB3495 treatment reduced atherosclerotic plaque
      formation in aorta and decreased the cholesteryl ester (CE) content by 57%.
      Treatment with KB3495 was also associated with a reduction of macrophage content
      in the atherosclerotic plaques and reduced serum levels of IL-1beta, TNFalpha, IL
      6, Interferon gamma, MCP-1 and M-CSF. Serum lipoprotein analysis showed no change
      in total cholesterol levels in ApoB-containing lipoproteins. KB3495 alone
      increased fecal BA excretion by 90%. The excretion of neutral sterols increased
      in all groups, with the largest increase in the combination group (350%). After
      25 weeks, the animals treated with KB3495 showed 50% lower CE levels in the skin
      and even further reductions were observed in the combination group where the CE
      levels were reduced by almost 95% as compared to controls. CONCLUSION: KB3495
      treatment reduced atherosclerosis independently of total cholesterol levels in
      ApoB-containing lipoproteins likely by stimulation of sterol excretion from the
      body and by inhibition of the inflammatory response.

PMID- 24324579
TI  - Depression in atrial fibrillation in the general population.
AB  - BACKGROUND: Initial evidence suggests that depressive symptoms are more frequent
      in patients with atrial fibrillation. Data from the general population are
      limited. METHODS AND RESULTS: In 10,000 individuals (mean age 56+/-11 years,
      49.4% women) of the population-based Gutenberg Health Study we assessed
      depression by the Patient Health Questionnaire (PHQ-9) and a history of
      depression in relation to manifest atrial fibrillation (n = 309 cases). The
      median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in
      atrial fibrillation individuals versus 3 (2/6) individuals without atrial
      fibrillation, P(X2-Test) = 0.32. Multivariable regression analyses of the
      severity of depressive symptoms in relation to atrial fibrillation in
      cardiovascular risk factor adjusted models revealed a relation of PHQ-9 values
      and atrial fibrillation (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01
      1.08; P = 0.023). The association was stronger for the somatic symptom dimension
      of depression (OR 1.08, 95% CI 1.02-1.15; P = 0.0085) than for cognitive symptoms
      (OR 1.05, 95% CI 0.98-1.11; P = 0.15). Results did not change markedly after
      additional adjustment for heart failure, partnership status or the inflammatory
      biomarker C-reactive protein. Both, self-reported physical health status, very
      good/good versus fair/bad, (OR 0.54, 95% CI 0.41-0.70; P<0.001) and mental health
      status (OR 0.61 (0.46-0.82); P = 0.0012) were associated with atrial fibrillation
      in multivariable-adjusted models. CONCLUSIONS: In a population-based sample we
      observed a higher burden of depressive symptoms driven by somatic symptom
      dimensions in individuals with atrial fibrillation. Depression was associated
      with a worse perception of physical or mental health status. Whether screening
      and treatment of depressive symptoms modulates disease progression and outcome
      needs to be shown.

PMID- 24324580
TI  - Inadequate exercise as a risk factor for sepsis mortality.
AB  - OBJECTIVE: Test whether inadequate exercise is related to sepsis mortality.
      RESEARCH DESIGN AND METHODS: Mortality surveillance of an epidemiological cohort
      of 155,484 National Walkers' and Runners' Health Study participants residing in
      the United States. Deaths were monitored for an average of 11.6-years using the
      National Death index through December 31, 2008. Cox proportional hazard analyses
      were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise
      (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths
      occurring within one year of the baseline survey were excluded. RESULTS: Sepsis
      was the underlying cause in 54 deaths (sepsis(underlying)) and a contributing
      cause in 184 deaths (sepsis(contributing)), or 238 total sepsis-related deaths
      (sepsis(total)). Inadequate exercise was associated with 2.24-fold increased risk
      for sepsis(underlying) (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased
      risk for sepsis(contributing) (95%CI: 1.51- to 2.92-fold, P<10(-4)), and 2.13
      fold increased risk for sepsis(total) (95%CI: 1.59- to 2.84-fold, P<10(-6)) when
      adjusted for age, sex, race, and cohort. The risk increase did not differ
      significantly between runners and walkers, by sex, or by age. Sepsis(total) risk
      was greater in diabetics (P = 10(-5)), cancer survivors (P = 0.0001), and heart
      attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004).
      The sepsis(total) risk associated with inadequate exercise persisted when further
      adjusted for diabetes, prior cancer, prior heart attack and waist circumference,
      and when excluding deaths with cancer, or cardiovascular, respiratory, or
      genitourinary disease as the underlying cause. Inadequate exercise also increased
      sepsis(total) risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8
      fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than
      the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46
      fold, P = 0.0006). CONCLUSION: Inadequate exercise is a risk factor for sepsis
      mortality, particular in diabetics.

PMID- 24324581
TI  - Isolation of cancer stem like cells from human adenosquamous carcinoma of the
      lung supports a monoclonal origin from a multipotential tissue stem cell.
AB  - There is increasing evidence that many solid tumors are hierarchically organized
      with the bulk tumor cells having limited replication potential, but are sustained
      by a stem-like cell that perpetuates the tumor. These cancer stem cells have been
      hypothesized to originate from transformation of adult tissue stem cells, or
      through re-acquisition of stem-like properties by progenitor cells. Adenosquamous
      carcinoma (ASC) is an aggressive type of lung cancer that contains a mixture of
      cells with squamous (cytokeratin 5+) and adenocarcinoma (cytokeratin 7+)
      phenotypes. The origin of these mixtures is unclear as squamous carcinomas are
      thought to arise from basal cells in the upper respiratory tract while
      adenocarcinomas are believed to form from stem cells in the bronchial alveolar
      junction. We have isolated and characterized cancer stem-like populations from
      ASC through application of selective defined culture medium initially used to
      grow human lung stem cells. Homogeneous cells selected from ASC tumor specimens
      were stably expanded in vitro. Primary xenografts and metastatic lesions derived
      from these cells in NSG mice fully recapitulate both the adenocarcinoma and
      squamous features of the patient tumor. Interestingly, while the CSLC all co
      expressed cytokeratins 5 and 7, most xenograft cells expressed either one, or
      neither, with <10% remaining double positive. We also demonstrated the potential
      of the CSLC to differentiate to multi-lineage structures with branching lung
      morphology expressing bronchial, alveolar and neuroendocrine markers in vitro.
      Taken together the properties of these ASC-derived CSLC suggests that ASC may
      arise from a primitive lung stem cell distinct from the bronchial-alveolar or
      basal stem cells. 

PMID- 24324582
TI  - High MUC2 expression in ovarian cancer is inversely associated with the M1/M2
      ratio of tumor-associated macrophages and patient survival time.
AB  - Mucin 2 (MUC2) is a mucin molecule aberrantly expressed by ovarian cancer cells.
      Previous in vitro studies have indicated that MUC2 promotes cancer growth and
      metastasis through a tumor-associated macrophage (TAM)-dependent mechanism.
      However, this mechanism has never been linked to clinical oncology, and its
      prognostic significance needed to be clarified. Here, we collected 102
      consecutive ovarian cancer specimens and used the multiple immuno-histo-chemical/
      fluorescent technique to determine the correlations between the MUC2 expression
      status, the ratio of M1/M2 TAMs and the densities of cyclooxygenase-2 (COX-2)(+)
      TAMs and COX-2(+) cancer cells. The Kaplan-Meier survival analysis and
      multivariate Cox regression analysis were used to evaluate the prognostic
      influences of these parameters. As a result, we found that the MUC2
      overexpression (immunostaining ++/+++) was significantly correlated with a
      reduced ratio of M1/M2 TAMs (p<0.001), an increased density of COX-2(+) TAMs
      (p<0.001) and an increased density of COX-2(+) cancer cells (p=0.017). Moreover,
      most of the M2 TAMs (93%-100%) and COX-2(+) TAMs (63%-89%) overlapped; and the
      COX-2(+) cancer cells were frequently observed near the COX-2(+) TAMs. In the Cox
      regression analysis, MUC2 overexpression was found to be an independent
      prognostic factor for ovarian cancer patients, of which the hazard ratio (HR) was
      2.354 (95% confidence interval (CI): 1.031-10.707, p=0.005). Also, the reduced
      ratio of M1/M2 TAMs and the increased densities of COX-2(+) TAMs and COX-2(+)
      cancer cells were demonstrated to be the predictors of poor prognosis, among
      which the reduced M1/M2 ratio possessed the highest HR (1.767, 95% CI: 1.061
      6.957, p=0.019). All these findings revealed that MUC2 can concurrently exert M2
      polarizing and COX-2-inducing effects on TAMs, by which it causes an imbalanced
      TAM M1-/M2-polarization pattern and induces local PGE2 synthesis (in both TAMs
      and cancer cells). The positive feedback between local PGE2 synthesis and TAM M2
      polarization accelerates ovarian cancer progression. 

PMID- 24324583
TI  - Microarray and RNAi analysis of P450s in Anopheles gambiae male and female
      steroidogenic tissues: CYP307A1 is required for ecdysteroid synthesis.
AB  - In insects, the steroid hormone 20-hydroxyecdysone (20E) coordinates major
      developmental transitions. While the first and the final steps of 20E
      biosynthesis are characterized, the pathway from 7-dehydrocholesterol to 5beta
      ketodiol, commonly referred as the "black box", remains hypothetical and whether
      there are still unidentified enzymes is unknown. The black box would include some
      oxidative steps, which are believed to be mediated by P450 enzymes. To identify
      new enzyme(s) involved in steroid synthesis, we analyzed by small-scale
      microarray the expression of all the genes encoding P450 enzymes of the malaria
      mosquito Anopheles gambiae in active steroidogenic organs of adults, ovaries from
      blood-fed females and male reproductive tracts, compared to inactive
      steroidogenic organs, ovaries from non-blood-fed females. Some genes encoding
      P450 enzymes were specifically overexpressed in female ovaries after a blood-meal
      or in male reproductive tracts but only three genes were found to be
      overexpressed in active steroidogenic organs of both females and males: cyp307a1,
      cyp4g16 and cyp6n1. Among these genes, only cyp307a1 has an expression pattern
      similar to other mosquito steroidogenic genes. Moreover, loss-of-function by
      transient RNAi targeting cyp307a1 disrupted ecdysteroid production demonstrating
      that this gene is required for ecdysteroid biosynthesis in Anopheles gambiae. 

PMID- 24324585
TI  - Cumulative human impacts on Mediterranean and Black Sea marine ecosystems:
      assessing current pressures and opportunities.
AB  - Management of marine ecosystems requires spatial information on current impacts.
      In several marine regions, including the Mediterranean and Black Sea, legal
      mandates and agreements to implement ecosystem-based management and spatial plans
      provide new opportunities to balance uses and protection of marine ecosystems.
      Analyses of the intensity and distribution of cumulative impacts of human
      activities directly connected to the ecological goals of these policy efforts are
      critically needed. Quantification and mapping of the cumulative impact of 22
      drivers to 17 marine ecosystems reveals that 20% of the entire basin and 60-99%
      of the territorial waters of EU member states are heavily impacted, with high
      human impact occurring in all ecoregions and territorial waters. Less than 1% of
      these regions are relatively unaffected. This high impact results from multiple
      drivers, rather than one individual use or stressor, with climatic drivers
      (increasing temperature and UV, and acidification), demersal fishing, ship
      traffic, and, in coastal areas, pollution from land accounting for a majority of
      cumulative impacts. These results show that coordinated management of key areas
      and activities could significantly improve the condition of these marine
      ecosystems. 

PMID- 24324584
TI  - Use of simulated patients to evaluate combined oral contraceptive dispensing
      practices of community pharmacists.
AB  - BACKGROUND: Combined oral contraceptive (COC) use is the most commonly used
      reversible method of birth control. The incorrect use of COCs is frequent and one
      of the most common causes of unintended pregnancies. Community pharmacists (CPs)
      are in a strategic position to improve COC use because they are the last health
      professional to interact with patients before drug use. OBJECTIVE: To evaluate
      the COC dispensing practices of CPs in a developing country. METHOD: A cross
      sectional study was conducted in community pharmacies of Assis and Ourinhos
      microregions, Brazil, between June 1, 2012, and October 30, 2012. Four simulated
      patients (SPs) (with counseled audio recording) visited community pharmacies with
      a prescription for Ciclo 21((r)) (a COC containing ethinyl estradiol 30 mcg +
      levonorgestrel 15 mcg). The audio recording of every SP visit was listened to
      independently by 3 researchers to evaluate the COC dispensing practice. The
      percentage of CPs who performed a screening for safe use of COCs (i.e., taking of
      patients' medical and family history, and measuring of blood pressure) and
      provided counseling, as well as the quality of the screening and counseling, were
      evaluated. RESULTS: Of the 185 CPs contacted, 41 (22.2%) agreed to participate in
      the study and finished the study protocol. Only 3 CPs asked the SP a question (1
      question asked by each professional), and all of the questions were closed-ended,
      viz., "do you smoke?" (n = 2) and "what is your age?" (n = 1). None of the CPs
      measured the patient's blood pressure. Six CPs provided counseling when
      dispensing COCs (drug dosing, 5 CPs; possible adverse effects, 2 CPs), and one CP
      provided counseling regarding both aspects. CONCLUSION: The CPs evaluated did not
      dispense COC appropriately and could influence in the occurrence of negatives
      therapeutic outcomes such as adverse effects and treatment failure.

PMID- 24324586
TI  - Acute histologic chorioamnionitis is a risk factor for adverse neonatal outcome
      in late preterm birth after preterm premature rupture of membranes.
AB  - BACKGROUND: The objective of this study was to determine whether acute histologic
      chorioamnionitis is associated with adverse neonatal outcomes in late preterm
      infants who were born after preterm PROM. METHODOLOGY/PRINCIPAL FINDINGS: The
      relationship between the presence of acute histologic chorioamnionitis and
      adverse neonatal outcome was examined in patients with preterm PROM who delivered
      singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation.
      Nonparametric statistics were used for data analysis. The frequency of acute
      histologic chorioamnionitis was 24% in patients with preterm PROM who delivered
      preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to
      mothers with histologic chorioamnionitis had significantly higher rates of
      adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic
      chorioamnionitis. This relationship remained significant after adjustment for
      gestational age at preterm PROM, gestational age at delivery, and exposure to
      antenatal corticosteroids. CONCLUSIONS/SIGNIFICANCE: The presence of acute
      histologic chorioamnionitis is associated with adverse neonatal outcome in late
      preterm infants born to mothers with preterm PROM.

PMID- 24324587
TI  - Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an
      unusual enzyme family.
AB  - The gene lmbB2 of the lincomycin biosynthetic gene cluster of Streptomyces
      lincolnensis ATCC 25466 was shown to code for an unusual tyrosine hydroxylating
      enzyme involved in the biosynthetic pathway of this clinically important
      antibiotic. LmbB2 was expressed in Escherichia coli, purified near to homogeneity
      and shown to convert tyrosine to 3,4-dihydroxyphenylalanine (DOPA). In contrast
      to the well-known tyrosine hydroxylases (EC 1.14.16.2) and tyrosinases (EC
      1.14.18.1), LmbB2 was identified as a heme protein. Mass spectrometry and Soret
      band-excited Raman spectroscopy of LmbB2 showed that LmbB2 contains heme b as
      prosthetic group. The CO-reduced differential absorption spectra of LmbB2 showed
      that the coordination of Fe was different from that of cytochrome P450 enzymes.
      LmbB2 exhibits sequence similarity to Orf13 of the anthramycin biosynthetic gene
      cluster, which has recently been classified as a heme peroxidase. Tyrosine
      hydroxylating activity of LmbB2 yielding DOPA in the presence of (6R)-5,6,7,8
      tetrahydro-L-biopterin (BH4) was also observed. Reaction mechanism of this unique
      heme peroxidases family is discussed. Also, tyrosine hydroxylation was confirmed
      as the first step of the amino acid branch of the lincomycin biosynthesis. 

PMID- 24324589
TI  - Development of a 3D coupled physical-biogeochemical model for the Marseille
      coastal area (NW Mediterranean Sea): what complexity is required in the coastal
      zone?
AB  - Terrestrial inputs (natural and anthropogenic) from rivers, the atmosphere and
      physical processes strongly impact the functioning of coastal pelagic ecosystems.
      The objective of this study was to develop a tool for the examination of these
      impacts on the Marseille coastal area, which experiences inputs from the Rhone
      River and high rates of atmospheric deposition. Therefore, a new 3D coupled
      physical/biogeochemical model was developed. Two versions of the biogeochemical
      model were tested, one model considering only the carbon (C) and nitrogen (N)
      cycles and a second model that also considers the phosphorus (P) cycle. Realistic
      simulations were performed for a period of 5 years (2007-2011). The model
      accuracy assessment showed that both versions of the model were able of capturing
      the seasonal changes and spatial characteristics of the ecosystem. The model also
      reproduced upwelling events and the intrusion of Rhone River water into the Bay
      of Marseille well. Those processes appeared to greatly impact this coastal
      oligotrophic area because they induced strong increases in chlorophyll-a
      concentrations in the surface layer. The model with the C, N and P cycles better
      reproduced the chlorophyll-a concentrations at the surface than did the model
      without the P cycle, especially for the Rhone River water. Nevertheless, the
      chlorophyll-a concentrations at depth were better represented by the model
      without the P cycle. Therefore, the complexity of the biogeochemical model
      introduced errors into the model results, but it also improved model results
      during specific events. Finally, this study suggested that in coastal
      oligotrophic areas, improvements in the description and quantification of the
      hydrodynamics and the terrestrial inputs should be preferred over increasing the
      complexity of the biogeochemical model. 

PMID- 24324588
TI  - Identify changes of brain regional homogeneity in bipolar disorder and unipolar
      depression using resting-state FMRI.
AB  - BACKGROUND: To identify changes in brain activation patterns in bipolar disorder
      (BD) and unipolar depression (UD) patients. METHODOLOGY/PRINCIPAL FINDINGS:
      Resting-state fMRI scans of 16 healthy controls, 17 BD and 16 UD patients were
      obtained. T-test of normalized regional homogeneity (ReHo) was performed in a
      voxel-by-voxel manner. A combined threshold of a = 0.05, minimum cluster volume
      of V = 10503 mm(3) (389 voxels) were used to determine ReHo differences between
      groups. In UD group, fMRI revealed ReHo increases in the left middle occipital
      lobe, right inferior parietal lobule, right precuneus and left convolution; and
      ReHo decreases in the left parahippocampalgyrus, right precentralgyrus, left
      postcentralgyrus, left precentralgyrus and left cingulated. In BD group, ReHo
      increases in the right insular cortex, left middle frontal gyrus, left precuneus,
      left occipital lobe, left parietal, left superior frontal gyrus and left
      thalamus; and ReHo decreases in the right anterior lobe of cerebellum, pons,
      right precentralgyrus, left postcentralgyrus, left inferior frontal gyrus, and
      right cingulate. There were some overlaps in ReHo profiles between UD and BD
      groups, but a marked difference was seen in the thalamus of BD.
      CONCLUSIONS/SIGNIFICANCE: The resting-state fMRI and ReHo mapping are a promising
      tool to assist the detection of functional deficits and distinguish clinical and
      pathophysiological signs of BD and UD.

PMID- 24324590
TI  - GSTM1 gene expression correlates to leiomyoma volume regression in response to
      mifepristone treatment.
AB  - Progesterone receptor modulators, such as mifepristone are useful and well
      tolerated in reducing leiomyoma volume although with large individual variation.
      The objective of this study was to investigate the molecular basis for the
      observed leiomyoma volume reduction, in response to mifepristone treatment and
      explore a possible molecular marker for the selective usage of mifepristone in
      leiomyoma patients. Premenopausal women (N = 14) were treated with mifepristone
      50 mg, every other day for 12 weeks prior to surgery. Women were arbitrarily sub
      grouped as good (N = 4), poor (N = 4) responders to treatment or intermediate
      respondents (N = 3). Total RNA was extracted from leiomyoma tissue, after
      surgical removal of the tumour and the differential expression of genes were
      analysed by microarray. The results were analysed using Ingenuity Pathway
      Analysis software. The glutathione pathway was the most significantly altered
      canonical pathway in which the glutathione-s transferase mu 1 (GSTM1) gene was
      significantly over expressed (+8.03 folds) among the good responders compared to
      non responders. This was further confirmed by Real time PCR (p = 0.024).
      Correlation of immunoreactive scores (IRS) for GSTM1 accumulation in leiomyoma
      tissue was seen with base line volume change of leiomyoma R = -0.8 (p = 0.011).
      Furthermore the accumulation of protein GSTM1 analysed by Western Blot correlated
      significantly with the percentual leiomyoma volume change R = -0.82 (p = 0.004).
      Deletion of the GSTM1 gene in leiomyoma biopsies was found in 50% of the
      mifepristone treated cases, with lower presence of the GSTM1 protein. The
      findings support a significant role for GSTM1 in leiomyoma volume reduction
      induced by mifepristone and explain the observed individual variation in this
      response. Furthermore the finding could be useful to further explore GSTM1 as a
      biomarker for tailoring medical treatment of uterine leiomyomas for optimizing
      the response to treatment. CLINICAL TRIALS IDENTIFIER: www.clinicaltrials.gov:
      NCT00579475, Protocol date: November 2004.
      http://clinicaltrials.gov/ct2/show/NCT00579475.

PMID- 24324591
TI  - Human endogenous retrovirus protein activates innate immunity and promotes
      experimental allergic encephalomyelitis in mice.
AB  - Multiple sclerosis (MS) is a complex multifactorial disease of the central
      nervous system (CNS) for which animal models have mainly addressed downstream
      immunopathology but not potential inducers of autoimmunity. In the absence of a
      pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly
      used in the form of complete Freund's adjuvant to induce autoimmunity to myelin
      proteins in Experimental Allergic Encephalomyelitis (EAE), an animal model for
      MS. The present study demonstrates that a protein from the human endogenous
      retrovirus HERV-W family (MSRV-Env) can be used instead of mycobacterial lysate
      to induce autoimmunity and EAE in mice injected with MOG, with typical anti
      myelin response and CNS lesions normally seen in this model. MSRV-Env was shown
      to induce proinflammatory response in human macrophage cells through TLR4
      activation pathway. The present results demonstrate a similar activation of
      murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice.
      In previous studies, MSRV-Env protein was reproducibly detected in MS brain
      lesions within microglia and perivascular macrophages. The present results are
      therefore likely to provide a model for MS, in which the upstream adjuvant
      triggering neuroinflammation is the one detected in MS active lesions. This model
      now allows pre-clinical studies with therapeutic agents targeting this endogenous
      retroviral protein in MS. 

PMID- 24324592
TI  - Asynchronicity of facial blood perfusion in migraine.
AB  - Asymmetrical changes in blood perfusion and asynchronous blood supply to head
      tissues likely contribute to migraine pathophysiology. Imaging was widely used in
      order to understand hemodynamic variations in migraine. However, mapping of blood
      pulsations in the face of migraineurs has not been performed so far. We used the
      Blood Pulsation Imaging (BPI) technique, which was recently developed in our
      group, to establish whether 2D-imaging of blood pulsations parameters can reveal
      new biomarkers of migraine. BPI characteristics were measured in migraineurs
      during the attack-free interval and compared to healthy subjects with and without
      a family history of migraine. We found a novel phenomenon of transverse waves of
      facial blood perfusion in migraineurs in contrast to healthy subjects who showed
      synchronous blood delivery to both sides of the face. Moreover, the amplitude of
      blood pulsations was symmetrically distributed over the face of healthy subjects,
      but asymmetrically in migraineurs and subjects with a family history of migraine.
      In the migraine patients we found a remarkable correlation between the side of
      unilateral headache and the direction of the blood perfusion wave. Our data
      suggest that migraine is associated with lateralization of blood perfusion and
      asynchronous blood pulsations in the facial area, which could be due to essential
      dysfunction of the autonomic vascular control in the face. These findings may
      further enhance our understanding of migraine pathophysiology and suggest new
      easily available biomarkers of this pathology. 

PMID- 24324593
TI  - Knowledge transfer on complex social interventions in public health: a scoping
      study.
AB  - OBJECTIVES: Scientific knowledge can help develop interventions that improve
      public health. The objectives of this review are (1) to describe the status of
      research on knowledge transfer strategies in the field of complex social
      interventions in public health and (2) to identify priorities for future research
      in this field. METHOD: A scoping study is an exploratory study. After searching
      databases of bibliographic references and specialized periodicals, we summarized
      the relevant studies using a predetermined assessment framework. In-depth
      analysis focused on the following items: types of knowledge transfer strategies,
      fields of public health, types of publics, types of utilization, and types of
      research specifications. RESULTS: From the 1,374 references identified, we
      selected 26 studies. The strategies targeted mostly administrators of
      organizations and practitioners. The articles generally dealt with instrumental
      utilization and most often used qualitative methods. In general, the bias risk
      for the studies is high. CONCLUSION: Researchers need to consider the
      methodological challenges in this field of research in order to improve
      assessment of more complex knowledge transfer strategies (when they exist), not
      just diffusion/dissemination strategies and conceptual and persuasive
      utilization.

PMID- 24324594
TI  - Spontaneous centralization of control in a network of company ownerships.
AB  - We introduce a model for the adaptive evolution of a network of company
      ownerships. In a recent work it has been shown that the empirical global network
      of corporate control is marked by a central, tightly connected "core" made of a
      small number of large companies which control a significant part of the global
      economy. Here we show how a simple, adaptive "rich get richer" dynamics can
      account for this characteristic, which incorporates the increased buying power of
      more influential companies, and in turn results in even higher control. We
      conclude that this kind of centralized structure can emerge without it being an
      explicit goal of these companies, or as a result of a well-organized strategy. 

PMID- 24324595
TI  - STX140, but not paclitaxel, inhibits mammary tumour initiation and progression in
      C3(1)/SV40 T/t-antigen transgenic mice.
AB  - Despite paclitxael's clinical success, treating hormone-refractory breast cancer
      remains challenging. Paclitaxel has a poor pharmacological profile, characterized
      by a low therapeutic index (TIX) caused by severe dose limiting toxicities, such
      as neutropenia and peripheral neuropathy. Consequently, new drugs are urgently
      required. STX140, a compound previously shown to have excellent efficacy against
      many tumors, is here compared to paclitaxel in three translational in vivo breast
      cancer models, a rat model of peripheral neuropathy, and through pharmacological
      testing. Three different in vivo mouse models of breast cancer were used; the
      metastatic 4T1 orthotopic model, the C3(1)/SV40 T-Ag model, and the MDA-MB-231
      xenograft model. To determine TIX and pharmacological profile of STX140, a
      comprehensive dosing regime was performed in mice bearing MDA-MD-231 xenografts.
      Finally, peripheral neuropathy was examined using a rat plantar thermal
      hyperalgesia model. In the 4T1 metastatic model, STX140 and paclitaxel
      significantly inhibited primary tumor growth and lung metastases. All C3(1)/SV40
      T-Ag mice in the control and paclitaxel treated groups developed palpable mammary
      cancer. STX140 blocked 47% of tumors developing and significantly inhibited
      growth of tumors that did develop. STX140 treatment caused a significant
      (P<0.001) survival advantage for animals in early and late intervention groups.
      Conversely, in C3(1)/SV40 T-Ag mice, paclitaxel failed to inhibit tumor growth
      and did not increase survival time. Furthermore, paclitaxel, but not STX140,
      induced significant peripheral neuropathy and neutropenia. These results show
      that STX140 has a greater anti-cancer efficacy, TIX, and reduced neurotoxicity
      compared to paclitaxel in C3(1)/SV40 T-Ag mice and therefore may be of
      significant benefit to patients with breast cancer. 

PMID- 24324596
TI  - Prognostic value and clinicopathological differences of HIFs in colorectal
      cancer: evidence from meta-analysis.
AB  - BACKGROUND: The prognostic value of HIFs in colorectal cancer was evaluated in a
      large number of studies, but the conclusions were inconclusive. Meanwhile,
      clinicopathologic differences of HIF-1alpha and HIF-2alpha were rarely compared
      in recent studies. METHODOLOGY: Identical search strategies were used to search
      relevant literatures in the PubMed and Web of Science databases. The prognostic
      significances and clinicopathological differences of HIFs in CRC were analyzed.
      PRINCIPAL FINDINGS: A total of 23 studies comprising 2984 CRC patients met the
      inclusion criteria. The results indicated that overexpressed HIFs were
      significantly associated with increase of mortality risk, including overall
      survival (OS) (HR 2.06 95%CI 1.55-2.74) and disease free survival (HR 2.84, 95%CI
      1.87-4.31). Subgroup analysis revealed that both overexpressed HIF-1alpha and HIF
      2alpha had correlations with worse prognosis. The pooled HRs were 2.01 (95% CI:
      1.55-2.6) and 2.07(95% CI: 1.01-4.26). Further subgroup analysis on HIF-1alpha
      was performed by study location, number of patients, quality score and cut-off
      value. The results showed that HIF-1alpha overexpression was significantly
      associated with poor OS, particularly in Asian countries (HR 2.3, 95% CI: 1.74
      3.01), while not in European or other countries. In addition, overexpression of
      HIF-1alpha was closely related with these clinicopathological features, including
      Dukes' stages (OR 0.39, 95% CI: 0.17-0.89), UICC stages (OR 0.42 95% CI: 0.3
      0.59), depth of invasion (OR 0.71, 95% CI: 0.51-0.99), lymphnode status (OR 0.49,
      95% CI: 0.32-0.73) and metastasis (OR 0.29, 95% CI: 0.11-0.81). While
      overexpression of HIF-2alpha was only associated with grade of differentiation
      (OR 0.48, 95% CI: 0.29-0.81). CONCLUSIONS: This study showed that both HIF-1alpha
      and HIF-2alpha overexpression were associated with an unfavorable prognosis. HIF
      1alpha overexpression seemed to be associated with worse prognosis in Asian
      countries. Additionally, HIF-1alpha and HIF-2alpha indicated distinct
      clinicopathologic features.

PMID- 24324597
TI  - Novel HCN2 mutation contributes to febrile seizures by shifting the channel's
      kinetics in a temperature-dependent manner.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated
      currents, known as I h, are involved in the control of rhythmic activity in
      neuronal circuits and in determining neuronal properties including the resting
      membrane potential. Recent studies have shown that HCN channels play a role in
      seizure susceptibility and in absence and limbic epilepsy including temporal lobe
      epilepsy following long febrile seizures (FS). This study focused on the
      potential contributions of abnormalities in the HCN2 isoform and their role in
      FS. A novel heterozygous missense mutation in HCN2 exon 1 leading to p.S126L was
      identified in two unrelated patients with FS. The mutation was inherited from the
      mother who had suffered from FS in a pedigree. To determine the effect of this
      substitution we conducted whole-cell patch clamp electrophysiology. We found that
      mutant channels had elevated sensitivity to temperature. More specifically, they
      displayed faster kinetics at higher temperature. Kinetic shift by change of
      temperature sensitivity rather than the shift of voltage dependence led to
      increased availability of I h in conditions promoting FS. Responses to cyclic AMP
      did not differ between wildtype and mutant channels. Thus, mutant HCN2 channels
      cause significant cAMP-independent enhanced availability of I h during high
      temperatures, which may contribute to hyperthermia-induced neuronal
      hyperexcitability in some individuals with FS. 

PMID- 24324598
TI  - A model for the early identification of sources of airborne pathogens in an
      outdoor environment.
AB  - BACKGROUND: Source identification in areas with outbreaks of airborne pathogens
      is often time-consuming and expensive. We developed a model to identify the most
      likely location of sources of airborne pathogens. METHODS: As a case study, we
      retrospectively analyzed three Q fever outbreaks in the Netherlands in 2009, each
      with suspected exposure from a single large dairy goat farm. Model input
      consisted only of case residential addresses, day of first clinical symptoms, and
      human population density data. We defined a spatial grid and fitted an
      exponentially declining function to the incidence-distance data of each grid
      point. For any grid point with a fit significant at the 95% confidence level, we
      calculated a measure of risk. For validation, we used results from abortion
      notifications, voluntary (2008) and mandatory (2009) bulk tank milk sampling at
      large (i.e. >50 goats and/or sheep) dairy farms, and non-systematic vaginal swab
      sampling at large and small dairy and non-dairy goat/sheep farms. In addition, we
      performed a two-source simulation study. RESULTS: Hotspots--areas most likely to
      contain the actual source--were identified at early outbreak stages, based on the
      earliest 2-10% of the case notifications. Distances between the hotspots and
      suspected goat farms varied from 300-1500 m. In regional likelihood rankings
      including all large dairy farms, the suspected goat farms consistently ranked
      first. The two-source simulation study showed that detection of sources is most
      clear if the distance between the sources is either relatively small or
      relatively large. CONCLUSIONS: Our model identifies the most likely location of
      sources in an airborne pathogen outbreak area, even at early stages. It can help
      to reduce the number of potential sources to be investigated by microbial testing
      and to allow rapid implementation of interventions to limit the number of human
      infections and to reduce the risk of source-to-source transmission.

PMID- 24324599
TI  - Deciphering ligand specificity of a Clostridium thermocellum family 35
      carbohydrate binding module (CtCBM35) for gluco- and galacto- substituted mannans
      and its calcium induced stability.
AB  - This study investigated the role of CBM35 from Clostridium thermocellum (CtCBM35)
      in polysaccharide recognition. CtCBM35 was cloned into pET28a (+) vector with an
      engineered His6 tag and expressed in Escherichia coli BL21 (DE3) cells. A
      homogenous 15 kDa protein was purified by immobilized metal ion chromatography
      (IMAC). Ligand binding analysis of CtCBM35 was carried out by affinity
      electrophoresis using various soluble ligands. CtCBM35 showed a manno-configured
      ligand specific binding displaying significant association with konjac
      glucomannan (Ka = 14.3*10(4) M(-1)), carob galactomannan (Ka = 12.4*10(4) M(-1))
      and negligible association (Ka = 12 uM(-1)) with insoluble mannan. Binding of
      CtCBM35 with polysaccharides which was calcium dependent exhibited two fold
      higher association in presence of 10 mM Ca(2+) ion with konjac glucomannan (Ka =
      41*10(4) M(-1)) and carob galactomannan (Ka = 30*10(4) M(-1)). The polysaccharide
      binding was further investigated by fluorescence spectrophotometric studies. On
      binding with carob galactomannan and konjac glucomannan the conformation of
      CtCBM35 changed significantly with regular 21 nm peak shifts towards lower
      quantum yield. The degree of association (K a) with konjac glucomannan and carob
      galactomannan, 14.3*10(4) M(-1) and 11.4*10(4) M(-1), respectively, corroborated
      the findings from affinity electrophoresis. The association of CtCBM35with konjac
      glucomannan led to higher free energy of binding (DeltaG) -25 kJ mole(-1) as
      compared to carob galactomannan (DeltaG) -22 kJ mole(-1). On binding CtCBM35 with
      konjac glucomannan and carob galactomannan the hydrodynamic radius (RH) as
      analysed by dynamic light scattering (DLS) study, increased to 8 nm and 6 nm,
      respectively, from 4.25 nm in absence of ligand. The presence of 10 mM Ca(2+)
      ions imparted stiffer orientation of CtCBM35 particles with increased RH of 4.52
      nm. Due to such stiffer orientation CtCBM35 became more thermostable and its
      melting temperature was shifted to 70 degrees C from initial 50 degrees C.

PMID- 24324600
TI  - Quantification of rare circulating tumor cells in non-small cell lung cancer by
      ligand-targeted PCR.
AB  - BACKGROUND: Quantification of circulating tumor cells (CTC) is valuable for
      evaluation of non-small cell lung cancer (NSCLC). The sensitivity of current
      methods constrains their use to detect rare CTCs in early stage. Here we evaluate
      a novel method, ligand-targeted polymerase chain reaction (LT-PCR), that can
      detect rare CTCs in NSCLC patients. METHODS: CTCs were enriched by immunomagnetic
      depletion of leukocytes and then labeled by a conjugate of a tumor-specific
      ligand and an oligonucleotide. After washing off free conjugates, the bound
      conjugates were stripped from CTCs and then analyzed by qPCR. To evaluate the
      clinical utility, blood samples were obtained from 72 NSCLC patients (33
      initially diagnosed and 39 on chemotherapy), 20 benign patients, and 24 healthy
      donors. RESULTS: Experiments with healthy blood spiked with tumor cells indicated
      the LT-PCR allows specific detection of CTC. The clinical study showed that the
      initially diagnosed patients have an average of 20.8 CTC units with metastatic
      diseases, 11.8 CTC units with localized diseases, and 6.0 CTC units with benign
      diseases. With the threshold of 8.5 CTC units, the assay can detect 80% of stage
      I/II, 67% of stage III, and 93% of stage IV cancer. With the benign patients and
      healthy donors as control group, the method can detect cancer with a sensitivity
      of 81.8% and a specificity of 93.2%. CONCLUSION: The LT-PCR would allow
      quantification of CTC in NSCLC patients at a more sensitive level, providing a
      potential tool for stratifying malignant lung diseases, especially at early
      stage.

PMID- 24324601
TI  - The role of Ctk1 kinase in termination of small non-coding RNAs.
AB  - Transcription termination in Saccharomyces cerevisiae can be performed by at
      least two distinct pathways and is influenced by the phosphorylation status of
      the carboxy-terminal domain (CTD) of RNA polymerase II (Pol II). Late termination
      of mRNAs is performed by the CPF/CF complex, the recruitment of which is
      dependent on CTD-Ser2 phosphorylation (Ser2P). Early termination of shorter
      cryptic unstable transcripts (CUTs) and small nucleolar/nuclear RNAs (sno/snRNAs)
      is performed by the Nrd1-Nab3-Sen1 (NNS) complex that binds phosphorylated CTD
      Ser5 (Ser5P) via the CTD-interacting domain (CID) of Nrd1p. In this study,
      mutants of the different termination pathways were compared by genome-wide
      expression analysis. Surprisingly, the expression changes observed upon loss of
      the CTD-Ser2 kinase Ctk1p are more similar to those derived from alterations in
      the Ser5P-dependent NNS pathway, than from loss of CTD-Ser2P binding factors.
      Tiling array analysis of ctk1Delta cells reveals readthrough at snoRNAs, at many
      cryptic unstable transcripts (CUTs) and stable uncharacterized transcripts
      (SUTs), but only at some mRNAs. Despite the suggested predominant role in
      termination of mRNAs, we observed that a CTK1 deletion or a Pol II CTD mutant
      lacking all Ser2 positions does not result in a global mRNA termination defect.
      Rather, termination defects in these strains are widely observed at NNS-dependent
      genes. These results indicate that Ctk1p and Ser2 CTD phosphorylation have a wide
      impact in termination of small non-coding RNAs but only affect a subset of mRNA
      coding genes. 

PMID- 24324602
TI  - Low birth weight, small for gestational age and preterm births before and after
      the economic collapse in Iceland: a population based cohort study.
AB  - OBJECTIVE: Infants born small for gestational age (SGA) or preterm have increased
      rates of perinatal morbidity and mortality. Stressful events have been suggested
      as potential contributors to preterm birth (PB) and low birth weight (LBW). We
      studied the effect of the 2008 economic collapse in Iceland on the risks of
      adverse birth outcomes. STUDY DESIGN: The study population constituted all
      Icelandic women giving birth to live-born singletons from January 1(st) 2006 to
      December 31(st) 2009. LBW infants were defined as those weighing <2500 grams at
      birth, PB infants as those born before 37 weeks of gestation and SGA as those
      with a birth weight for gestational age more than 2 standard deviations (SD's)
      below the mean according to the Swedish fetal growth curve. We used logistic
      regression analysis to estimate odds ratios [OR] and corresponding 95 percent
      confidence intervals [95% CI] of adverse birth outcomes by exposure to calendar
      time of the economic collapse, i.e. after October 6(th) 2008. RESULTS: Compared
      to the preceding period, we observed an increased adjusted odds in LBW-deliveries
      following the collapse (aOR = 1.24, 95% CI [1.02, 1.52]), particularly among
      infants born to mothers younger than 25 years (aOR = 1.85, 95% CI [1.25, 2.72])
      and not working mothers (aOR = 1.61, 95% CI [1.10, 2.35]). Similarly, we found a
      tendency towards higher incidence of SGA-births (aOR = 1.14, 95% CI [0.86, 1.51])
      particularly among children born to mothers younger than 25 years (aOR = 1.87,
      95% CI [1.09, 3.23]) and not working mothers (aOR = 1.86, 95% CI [1.09, 3.17]).
      No change in risk of PB was observed. The increase of LBW was most distinct 6-9
      months after the collapse. CONCLUSION: The results suggest an increase in risk of
      LBW shortly after the collapse of the Icelandic national economy. The increase in
      LBW seems to be driven by reduced fetal growth rate rather than shorter
      gestation.

PMID- 24324603
TI  - Bayesian centroid estimation for motif discovery.
AB  - Biological sequences may contain patterns that signal important biomolecular
      functions; a classical example is regulation of gene expression by transcription
      factors that bind to specific patterns in genomic promoter regions. In motif
      discovery we are given a set of sequences that share a common motif and aim to
      identify not only the motif composition, but also the binding sites in each
      sequence of the set. We propose a new centroid estimator that arises from a
      refined and meaningful loss function for binding site inference. We discuss the
      main advantages of centroid estimation for motif discovery, including
      computational convenience, and how its principled derivation offers further
      insights about the posterior distribution of binding site configurations. We also
      illustrate, using simulated and real datasets, that the centroid estimator can
      differ from the traditional maximum a posteriori or maximum likelihood
      estimators. 

PMID- 24324604
TI  - Seroprevalence of human enterovirus 71 and coxsackievirus A16 in Guangdong,
      China, in pre- and post-2010 HFMD epidemic period.
AB  - BACKGROUND: Human Enterovirus 71 and Coxsackie A16 have caused many outbreaks in
      the last decade in mainland China, resulting in thousands of fatal cases.
      Seroepidemiology which provides important information to document population
      immunity is rare in China. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional
      study of Enterovirus 71 (EV71) and Coxsackie A16 (CA16) seroprevalence was
      carried out in Guangdong, China, pre- and post- the 2010 hand, foot and mouth
      disease (HFMD) epidemic period. The levels of EV71 and CA16 specific antibodies
      were evaluated by a microneutralization test and the geometric mean titer (GMT)
      was calculated and compared. Our results indicated frequent infection by EV71 and
      CA16 in Guangdong before the 2010 epidemic. Only EV71 neutralizing antibody but
      not CA16 seroprevalence was significantly increased after the 2010 HFMD epidemic.
      Children less than 3 years old especially those aged 2 years showed the lowest
      positive rates for EV71 and CA16 NA before epidemic and the most significantly
      increased EV71 seroprevalence after epidemic. CA16 GMT values declined after the
      2010 epidemic. CONCLUSIONS: These results indicate EV71 was the major pathogen of
      HFMD in Guangdong during the 2010 epidemic. The infection occurs largely in
      children less than 3 years, who should have first priority to receive an EV71
      vaccine.

PMID- 24324605
TI  - Association between infancy BMI peak and body composition and blood pressure at
      age 5-6 years.
AB  - INTRODUCTION: The development of overweight is often measured with the body mass
      index (BMI). During childhood the BMI curve has two characteristic points: the
      adiposity rebound at 6 years and the BMI peak at 9 months of age. In this study,
      the associations between the BMI peak and body composition measures and blood
      pressure at age 5-6 years were investigated. METHODS: Measurements from the
      Amsterdam Born Children and their Development (ABCD) study were available for
      this study. Blood pressure (systolic and diastolic) and body composition measures
      (BMI, waist-to-height ratio, fat percentage) were gathered during a health check
      at about 6 years of age (n = 2822). All children had multiple BMI measurements
      between the 0-4 years of age. For boys and girls separately, child-specific BMI
      peaks were extracted from mixed effect models. Associations between the estimated
      BMI peak and the health check measurements were analysed with linear models. In
      addition, we investigated the potential use of the BMI at 9 months as a surrogate
      measure for the magnitude of the BMI peak. RESULTS: After correction for the
      confounding effect of fetal growth, both timing and magnitude of the BMI peak
      were significantly and positively associated (p<0.001) with all body composition
      measures at the age of 5-6 years. The BMI peak showed no direct association with
      blood pressure at the age 5-6 year, but was mediated by the current BMI. The
      correlation between the magnitude of the BMI peak and BMI at 9 months was
      approximately 0.93 and similar associations with the measures at 5-6 years were
      found. CONCLUSION: The magnitude of the BMI peak was associated with body
      composition measures at 5-6 years of age. Moreover, the BMI at 9 months could be
      used as surrogate measure for the magnitude of the BMI peak.

PMID- 24324606
TI  - Quantitative agent based model of user behavior in an Internet discussion forum.
AB  - The paper presents an agent based simulation of opinion evolution, based on a
      nonlinear emotion/information/opinion (E/I/O) individual dynamics, to an actual
      Internet discussion forum. The goal is to reproduce the results of two-year long
      observations and analyses of the user communication behavior and of the expressed
      opinions and emotions, via simulations using an agent based model. The model
      allowed to derive various characteristics of the forum, including the
      distribution of user activity and popularity (outdegree and indegree), the
      distribution of length of dialogs between the participants, their political
      sympathies and the emotional content and purpose of the comments. The parameters
      used in the model have intuitive meanings, and can be translated into
      psychological observables. 

PMID- 24324607
TI  - The association of maximum body weight on the development of type 2 diabetes and
      microvascular complications: MAXWEL study.
AB  - BACKGROUND: Obesity precedes the development of type 2 diabetes (T2D). However,
      the relationship between the magnitude and rate of weight gain to T2D development
      and complications, especially in non-White populations, has received less
      attention. METHODS AND FINDINGS: We determined the association of rate and
      magnitude of weight gain to age at T2D diagnosis (Age(T2D)), HbA1c at T2D
      diagnosis (HbA1c(T2D)), microalbuminuria, and diabetic retinopathy after
      adjusting for sex, BMI at age 20 years, lifestyles, family history of T2D and/or
      blood pressure and lipids in 2164 Korean subjects aged >=30 years and newly
      diagnosed with diabetes. Body weight at age 20 years (Wt(20y)) was obtained by
      recall or from participants' medical, school, or military records. Participants
      recalled their maximum weight (Wt(max)) prior to T2D diagnosis and age at maximum
      weight (Age(max_wt)). The rate of weight gain (Rate(max_wt)) was calculated from
      magnitude of weight gain (DeltaWt = Wt(max)-Wt(20y)) divided by DeltaTime
      (Age(max_wt) -20 years). The mean Age(max_wt) and Age(T2D) were 41.5+/-10.9 years
      and 50.1+/-10.5 years, respectively. The Wt(20y) and Wt(max) were 59.9+/-10.5 kg
      and 72.9+/-11.4 kg, respectively. The Rate(max_wt) was 0.56+/-0.50 kg/year. After
      adjusting for risk factors, greater DeltaWt and higher Rate(max_wt) were
      significantly associated with earlier Age(T2D), higher HbA1c(T2D) after
      additional adjusting for Age(T2D), and microalbuminuria after further adjusting
      for HbA1c(T2D) and lipid profiles. Greater DeltaWt and higher Rate(max_wt) were
      also significantly associated with diabetic retinopathy. CONCLUSIONS: This
      finding supports public health recommendations to reduce the risk of T2D and its
      complications by preventing weight gain from early adulthood.

PMID- 24324608
TI  - Extra cellular matrix derived metabolite regulates angiogenesis by FasL mediated
      apoptosis.
AB  - OBJECT: Antiangiogenic treatments are beginning to give promising outcomes in
      many vascular diseases including tumor angiogenesis. In this current study the
      antiangiogenic and pro-apoptotic actions of alpha1(IV)NC1 and its N- and C-
      peptides alpha1S1(IV)NC1, alpha1S2(IV)NC1 were investigated in-vitro and in-vivo.
      STUDY METHOD: Endothelial cells (ECs) were treated with alpha1(IV)NC1,
      alpha1S1(IV)NC1, alpha1S2(IV)NC1 and in-vitro proliferation, migration, tube
      formation and apoptotic assays were executed. FasL, Fas, Caspase-8, -3 and PARP
      activations were studied using immunoblotting analysis using specific antibodies.
      Also the in-vivo antiangiogenic and pro-apoptotic effects were tested using
      alpha1(IV)NC1 in a mice model. RESULTS: Like alpha1(IV)NC1, its N- and C-
      terminal alpha1S2(IV)NC1 and alpha1S1(IV)NC1 domains posses anti-proliferative,
      pro-apoptotic activity and inhibit ECs migration and tube formation in-vitro.
      Both alpha1S1(IV)NC1 and alpha1S2(IV)NC1 domains promote apoptosis by activating
      FasL and down stream apoptotic events including activation of caspase-8, -3 and
      PARP cleavage in a dose dependent manner in-vitro in ECs. Tumors in mice showed
      apoptotic TUNEL positive microvasculature upon alpha1(IV)NC1 treatment,
      indicating inhibition of tumor angiogenesis and tumor growth. Further, the
      antitumor activity of alpha1(IV)NC1 was abrogated when caspase-3 inhibitor was
      used. These results conform additional properties of alpha1(IV)NC1 as an
      endogenous angioinhibitor that induces apoptosis in-vitro and in-vivo by
      activating FasL mediated caspase-3. SIGNIFICANCE: alpha1(IV)NC1 and its N- and C-
      terminal alpha1S1(IV)NC1 and alpha1S2(IV)NC1 domains also posses pro-apoptotic
      and angioinhibitory activity in-vitro and in-vivo. alpha1(IV)NC1 regulates tumor
      angiogenesis by activating FasL mediated apoptosis in-vitro and in-vivo. These
      results demonstrate that alpha1(IV)NC1 and its peptides inhibit neo-vascular
      diseases.

PMID- 24324609
TI  - Pain and pessimism: dairy calves exhibit negative judgement bias following hot
      iron disbudding.
AB  - Pain is defined as an unpleasant sensory and emotional experience associated with
      actual or potential tissue damage, but emotional states are difficult to directly
      assess in animals. Researchers have assessed pain using behavioural and
      physiological measures, but these approaches are limited to understanding the
      arousal rather than valence of the emotional experience. Cognitive bias tasks
      show that depressed humans judge ambiguous events negatively and this technique
      has been applied to assess emotional states in animals. However, limited research
      has examined how pain states affect cognitive processes in animals. Here we
      present the first evidence of cognitive bias in response to pain in any non-human
      species. In two experiments, dairy calves (n = 17) were trained to respond
      differentially to red and white video screens and then tested with unreinforced
      ambiguous colours in two or three test sessions before and two sessions after the
      routine practice of hot-iron disbudding. After disbudding calves were more likely
      to judge ambiguous colours as negative. This 'pessimistic' bias indicates that
      post-operative pain following hot-iron disbudding results in a negative change in
      emotional state. 

PMID- 24324610
TI  - Cockroaches probably cleaned up after dinosaurs.
AB  - Dinosaurs undoubtedly produced huge quantities of excrements. But who cleaned up
      after them? Dung beetles and flies with rapid development were rare during most
      of the Mesozoic. Candidates for these duties are extinct cockroaches
      (Blattulidae), whose temporal range is associated with herbivorous dinosaurs. An
      opportunity to test this hypothesis arises from coprolites to some extent
      extruded from an immature cockroach preserved in the amber of Lebanon, studied
      using synchrotron X-ray microtomography. 1.06% of their volume is filled by
      particles of wood with smooth edges, in which size distribution directly supports
      their external pre-digestion. Because fungal pre-processing can be excluded based
      on the presence of large particles (combined with small total amount of wood) and
      absence of damages on wood, the likely source of wood are herbivore feces.
      Smaller particles were broken down biochemically in the cockroach hind gut, which
      indicates that the recent lignin-decomposing termite and cockroach endosymbionts
      might have been transferred to the cockroach gut upon feeding on dinosaur feces. 

PMID- 24324611
TI  - Cryptic speciation patterns in Iranian rock lizards uncovered by integrative
      taxonomy.
AB  - While traditionally species recognition has been based solely on morphological
      differences either typological or quantitative, several newly developed methods
      can be used for a more objective and integrative approach on species
      delimitation. This may be especially relevant when dealing with cryptic species
      or species complexes, where high overall resemblance between species is coupled
      with comparatively high morphological variation within populations. Rock lizards,
      genus Darevskia, are such an example, as many of its members offer few diagnostic
      morphological features. Herein, we use a combination of genetic, morphological
      and ecological criteria to delimit cryptic species within two species complexes,
      D. chlorogaster and D. defilippii, both distributed in northern Iran. Our
      analyses are based on molecular information from two nuclear and two
      mitochondrial genes, morphological data (15 morphometric, 16 meristic and four
      categorical characters) and eleven newly calculated spatial environmental
      predictors. The phylogeny inferred for Darevskia confirmed monophyly of each
      species complex, with each of them comprising several highly divergent clades,
      especially when compared to other congeners. We identified seven candidate
      species within each complex, of which three and four species were supported by
      Bayesian species delimitation within D. chlorogaster and D. defilippii,
      respectively. Trained with genetically determined clades, Ecological Niche
      Modeling provided additional support for these cryptic species. Especially those
      within the D. defilippii-complex exhibit well-differentiated niches. Due to
      overall morphological resemblance, in a first approach PCA with mixed variables
      only showed the separation between the two complexes. However, MANCOVA and
      subsequent Discriminant Analysis performed separately for both complexes allowed
      for distinction of the species when sample size was large enough, namely within
      the D. chlorogaster-complex. In conclusion, the results support four new species,
      which are described herein. 

PMID- 24324612
TI  - Epidermal growth-factor-induced transcript isoform variation drives mammary cell
      migration.
AB  - Signal-induced transcript isoform variation (TIV) includes alternative promoter
      usage as well as alternative splicing and alternative polyadenylation of mRNA. To
      assess the phenotypic relevance of signal-induced TIV, we employed exon arrays
      and breast epithelial cells, which migrate in response to the epidermal growth
      factor (EGF). We show that EGF rapidly--within one hour--induces widespread TIV
      in a significant fraction of the transcriptome. Importantly, TIV characterizes
      many genes that display no differential expression upon stimulus. In addition,
      similar EGF-dependent changes are shared by a panel of mammary cell lines. A
      functional screen, which utilized isoform-specific siRNA oligonucleotides,
      indicated that several isoforms play essential, non-redundant roles in EGF
      induced mammary cell migration. Taken together, our findings highlight the
      importance of TIV in the rapid evolvement of a phenotypic response to
      extracellular signals.

PMID- 24324613
TI  - Rb suppresses collective invasion, circulation and metastasis of breast cancer
      cells in CD44-dependent manner.
AB  - Basal-like breast carcinomas (BLCs) present with extratumoral lymphovascular
      invasion, are highly metastatic, presumably through a hematogenous route, have
      augmented expression of CD44 oncoprotein and relatively low levels of
      retinoblastoma (Rb) tumor suppressor. However, the causal relation among these
      features is not clear. Here, we show that Rb acts as a key suppressor of multiple
      stages of metastatic progression. Firstly, Rb suppresses collective cell
      migration (CCM) and CD44-dependent formation of F-actin positive protrusions in
      vitro and cell-cluster based lymphovascular invasion in vivo. Secondly, Rb
      inhibits the release of single cancer cells and cell clusters into the
      hematogenous circulation and subsequent metastatic growth in lungs. Finally, CD44
      expression is required for collective motility and all subsequent stages of
      metastatic progression initiated by loss of Rb function. Altogether, our results
      suggest that Rb/CD44 pathway is a crucial regulator of CCM and metastatic
      progression of BLCs and a promising target for anti-BLCs therapy. 

PMID- 24324614
TI  - Elevated alanine aminotransferase is strongly associated with incident metabolic
      syndrome: a meta-analysis of prospective studies.
AB  - BACKGROUND: The incidence of metabolic syndrome (MetS) is rapidly increasing
      worldwide and associated with alanine aminotransferase (ALT) activity. However,
      the impact of ALT activity on MetS incidence is inconsistent in published
      literature. We therefore estimated the association between elevated ALT activity
      and incident MetS through a meta-analysis of prospective cohort studies.
      METHODS/PRINCIPAL FINDINGS: All published prospective cohort studies on the
      association between elevated ALT activity and incident MetS were retrieved from
      Pubmed, Embase, and the Institute for Scientific Information (ISI). In all, seven
      prospective cohort studies, with 31545 participants and 2873 cases of incident
      MetS were recruited. If there was insignificant heterogeneity (P-value>0.05 and
      I(2)<50%), the fixed-effect model was used to calculate the pooled relative risks
      (RRs) of incident MetS induced by raised ALT. Otherwise, the random-effect model
      was used. The calculated RR was 1.81 (95% confidence interval [CI]: 1.49-2.14)
      when the incidence of MetS was compared between the highest versus the lowest
      classification of ALT activities. The pooled RR was 1.13 (95% CI: 1.11-1.16) in
      dose-response analysis with 5 units per liter (U/l) of ALT increment. Subgroup
      analysis suggested that gender disparity might be the main origin of
      heterogeneity in overall analysis (P = 0.007 between RRs of gender-specific
      subgroups evaluated with 5 U/l increments of ALT). Women had a higher dose
      response risk of MetS incidence (1.38, 95% CI: 1.20-1.55) than men. Furthermore,
      sensitivity analysis confirmed the stability of results. No publication bias was
      found in our meta-analysis. CONCLUSIONS/SIGNIFICANCE: Current evidence from
      prospective studies supports the association between ALT elevation and increasing
      MetS incidence. This association is closer and more consistent in female
      population. Further studies are needed to confirm this association and to
      investigate the potential mechanism of ALT activity on MetS occurrence.

PMID- 24324616
TI  - Glial cell line-derived neurotrophic factor (GDNF) as a novel candidate gene of
      anxiety.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for
      dopaminergic neurons with promising therapeutic potential in Parkinson's disease.
      A few association analyses between GDNF gene polymorphisms and psychiatric
      disorders such as schizophrenia, attention deficit hyperactivity disorder and
      drug abuse have also been published but little is known about any effects of
      these polymorphisms on mood characteristics such as anxiety and depression. Here
      we present an association study between eight (rs1981844, rs3812047, rs3096140,
      rs2973041, rs2910702, rs1549250, rs2973050 and rs11111) GDNF single nucleotide
      polymorphisms (SNPs) and anxiety and depression scores measured by the Hospital
      Anxiety and Depression Scale (HADS) on 708 Caucasian young adults with no
      psychiatric history. Results of the allele-wise single marker association
      analyses provided significant effects of two single nucleotide polymorphisms on
      anxiety scores following the Bonferroni correction for multiple testing (p =
      0.00070 and p = 0.00138 for rs3812047 and rs3096140, respectively), while no such
      result was obtained on depression scores. Haplotype analysis confirmed the role
      of these SNPs; mean anxiety scores raised according to the number of risk alleles
      present in the haplotypes (p = 0.00029). A significant sex-gene interaction was
      also observed since the effect of the rs3812047 A allele as a risk factor of
      anxiety was more pronounced in males. In conclusion, this is the first
      demonstration of a significant association between the GDNF gene and mood
      characteristics demonstrated by the association of two SNPs of the GDNF gene
      (rs3812047 and rs3096140) and individual variability of anxiety using self-report
      data from a non-clinical sample. 

PMID- 24324615
TI  - Simultaneous transcriptional profiling of bacteria and their host cells.
AB  - We developed an RNA-Seq-based method to simultaneously capture prokaryotic and
      eukaryotic expression profiles of cells infected with intracellular bacteria. As
      proof of principle, this method was applied to Chlamydia trachomatis-infected
      epithelial cell monolayers in vitro, successfully obtaining transcriptomes of
      both C. trachomatis and the host cells at 1 and 24 hours post-infection.
      Chlamydiae are obligate intracellular bacterial pathogens that cause a range of
      mammalian diseases. In humans chlamydiae are responsible for the most common
      sexually transmitted bacterial infections and trachoma (infectious blindness).
      Disease arises by adverse host inflammatory reactions that induce tissue damage &
      scarring. However, little is known about the mechanisms underlying these
      outcomes. Chlamydia are genetically intractable as replication outside of the
      host cell is not yet possible and there are no practical tools for routine
      genetic manipulation, making genome-scale approaches critical. The early
      timeframe of infection is poorly understood and the host transcriptional response
      to chlamydial infection is not well defined. Our simultaneous RNA-Seq method was
      applied to a simplified in vitro model of chlamydial infection. We discovered a
      possible chlamydial strategy for early iron acquisition, putative immune
      dampening effects of chlamydial infection on the host cell, and present a
      hypothesis for Chlamydia-induced fibrotic scarring through runaway positive
      feedback loops. In general, simultaneous RNA-Seq helps to reveal the complex
      interplay between invading bacterial pathogens and their host mammalian cells and
      is immediately applicable to any bacteria/host cell interaction. 

PMID- 24324617
TI  - Transcriptional activation of Mina by Sp1/3 factors.
AB  - Mina is an epigenetic gene regulatory protein known to function in multiple
      physiological and pathological contexts, including pulmonary inflammation, cell
      proliferation, cancer and immunity. We showed previously that the level of Mina
      gene expression is subject to natural genetic variation linked to 21 SNPs
      occurring in the Mina 5' region. In order to explore the mechanisms regulating
      Mina gene expression, we set out to molecularly characterize the Mina promoter in
      the region encompassing these SNPs. We used three kinds of assays--reporter, gel
      shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment
      spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a
      pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1).
      Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3
      transcription factors trigger Mina expression through additive activity targeted
      to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results
      set the stage for comprehensive analysis of Mina gene regulation from the context
      of tissue specificity, the impact of inherited genetic variation and the nature
      of upstream signaling pathways.

PMID- 24324618
TI  - Congenital sensorineural deafness in dalmatian dogs associated with quantitative
      trait loci.
AB  - A genome-wide association study (GWAS) was performed for 235 Dalmatian dogs using
      the canine Illumina high density bead chip to identify quantitative trait loci
      (QTL) associated with canine congenital sensorineural deafness (CCSD). Data
      analysis was performed for all Dalmatian dogs and in addition, separately for
      brown-eyed and blue-eyed dogs because of the significant influence of eye colour
      on CCSD in Dalmatian dogs. Mixed linear model analysis (MLM) revealed seven QTL
      with experiment-wide significant associations (-log10P>5.0) for CCSD in all
      Dalmatian dogs. Six QTL with experiment-wide significant associations for CCSD
      were found in brown-eyed Dalmatian dogs and in blue-eyed Dalmatian dogs, four
      experiment-wide significant QTL were detected. The experiment-wide CCSD
      associated SNPs explained 82% of the phenotypic variance of CCSD. Five CCSD-loci
      on dog chromosomes (CFA) 6, 14, 27, 29 and 31 were in close vicinity of genes
      shown as causative for hearing loss in human and/or mouse.

PMID- 24324619
TI  - PMS: a panoptic motif search tool.
AB  - BACKGROUND: Identification of DNA/Protein motifs is a crucial problem for
      biologists. Computational techniques could be of great help in this
      identification. In this direction, many computational models for motifs have been
      proposed in the literature. METHODS: One such important model is the (l,d) motif
      model. In this paper we describe a motif search web tool that predominantly
      employs this motif model. This web tool exploits the state-of-the art algorithms
      for solving the (l,d) motif search problem. RESULTS: The online tool has been
      helping scientists identify many unknown motifs. Many of our predictions have
      been successfully verified as well. We hope that this paper will expose this
      crucial tool to many more scientists. AVAILABILITY AND REQUIREMENTS: Project
      name: PMS--Panoptic Motif Search Tool. Project home page:
      http://pms.engr.uconn.edu or http://motifsearch.com. Licence: PMS tools will be
      readily available to any scientist wishing to use it for non-commercial purposes,
      without restrictions. The online tool is freely available without login.

PMID- 24324620
TI  - Spaceflight enhances cell aggregation and random budding in Candida albicans.
AB  - This study presents the first global transcriptional profiling and phenotypic
      characterization of the major human opportunistic fungal pathogen, Candida
      albicans, grown in spaceflight conditions. Microarray analysis revealed that C.
      albicans subjected to short-term spaceflight culture differentially regulated 452
      genes compared to synchronous ground controls, which represented 8.3% of the
      analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell
      aggregation (similar to flocculation), which was validated by microscopic and
      flow cytometry analysis. We also observed enhanced random budding of spaceflight
      cultured cells as opposed to bipolar budding patterns for ground samples, in
      accordance with the gene expression data. Furthermore, genes involved in
      antifungal agent and stress resistance were differentially regulated in
      spaceflight, including induction of ABC transporters and members of the major
      facilitator family, downregulation of ergosterol-encoding genes, and upregulation
      of genes involved in oxidative stress resistance. Finally, downregulation of
      genes involved in actin cytoskeleton was observed. Interestingly, the
      transcriptional regulator Cap1 and over 30% of the Cap1 regulon was
      differentially expressed in spaceflight-cultured C. albicans. A potential role
      for Cap1 in the spaceflight response of C. albicans is suggested, as this
      regulator is involved in random budding, cell aggregation, and oxidative stress
      resistance; all related to observed spaceflight-associated changes of C.
      albicans. While culture of C. albicans in microgravity potentiates a global
      change in gene expression that could induce a virulence-related phenotype, no
      increased virulence in a murine intraperitoneal (i.p.) infection model was
      observed under the conditions of this study. Collectively, our data represent an
      important basis for the assessment of the risk that commensal flora could play
      during human spaceflight missions. Furthermore, since the low fluid-shear
      environment of microgravity is relevant to physical forces encountered by
      pathogens during the infection process, insights gained from this study could
      identify novel infectious disease mechanisms, with downstream benefits for the
      general public. 

PMID- 24324621
TI  - Reliable neuronal systems: the importance of heterogeneity.
AB  - For every engineer it goes without saying: in order to build a reliable system we
      need components that consistently behave precisely as they should. It is also
      well known that neurons, the building blocks of brains, do not satisfy this
      constraint. Even neurons of the same type come with huge variances in their
      properties and these properties also vary over time. Synapses, the connections
      between neurons, are highly unreliable in forwarding signals. In this paper we
      argue that both these fact add variance to neuronal processes, and that this
      variance is not a handicap of neural systems, but that instead predictable and
      reliable functional behavior of neural systems depends crucially on this
      variability. In particular, we show that higher variance allows a recurrently
      connected neural population to react more sensitively to incoming signals, and
      processes them faster and more energy efficient. This, for example, challenges
      the general assumption that the intrinsic variability of neurons in the brain is
      a defect that has to be overcome by synaptic plasticity in the process of
      learning.

PMID- 24324622
TI  - Expression and function of methylthioadenosine phosphorylase in chronic liver
      disease.
AB  - To study expression and function of methylthioadenosine phosphorylase (MTAP), the
      rate-limiting enzyme in the methionine and adenine salvage pathway, in chronic
      liver disease. DESIGN: MTAP expression was analyzed by qRT-PCR, Western blot and
      immunohistochemical analysis. Levels of MTA were determined by liquid
      chromatography-tandem mass spectrometry. RESULTS: MTAP was downregulated in
      hepatocytes in murine fibrosis models and in patients with chronic liver disease,
      leading to a concomitant increase in MTA levels. In contrast, activated hepatic
      stellate cells (HSCs) showed strong MTAP expression in cirrhotic livers. However,
      also MTA levels in activated HSCs were significantly higher than in hepatocytes,
      and there was a significant correlation between MTA levels and collagen
      expression in diseased human liver tissue indicating that activated HSCs
      significantly contribute to elevated MTA in diseased livers. MTAP suppression by
      siRNA resulted in increased MTA levels, NFkappaB activation and apoptosis
      resistance, while overexpression of MTAP caused the opposite effects in HSCs. The
      anti-apoptotic effect of low MTAP expression and high MTA levels, respectively,
      was mediated by induced expression of survivin, while inhibition of survivin
      abolished the anti-apoptotic effect of MTA on HSCs. Treatment with a DNA
      demethylating agent induced MTAP and reduced survivin expression, while oxidative
      stress reduced MTAP levels but enhanced survivin expression in HSCs. CONCLUSION:
      MTAP mediated regulation of MTA links polyamine metabolism with NFkappaB
      activation and apoptosis in HSCs. MTAP and MTAP modulating mechanisms appear as
      promising prognostic markers and therapeutic targets for hepatic fibrosis.

PMID- 24324623
TI  - Who needs cream and sugar when there is eco-labeling? Taste and willingness to
      pay for "eco-friendly" coffee.
AB  - Participants tasted two cups of coffee, decided which they preferred, and then
      rated each coffee. They were told (in lure) that one of the cups contained "eco
      friendly" coffee while the other did not, although the two cups contained
      identical coffee. In Experiments 1 and 3, but not in Experiment 2, the
      participants were also told which cup contained which type of coffee before they
      tasted. The participants preferred the taste of, and were willing to pay more
      for, the "eco-friendly" coffee, at least those who scored high on a questionnaire
      on attitudes toward sustainable consumer behavior (Experiment 1). High
      sustainability consumers were also willing to pay more for "eco-friendly" coffee,
      even when they were told, after their decision, that they preferred the non
      labeled alternative (Experiment 2). Moreover, the eco-label effect does not
      appear to be a consequence of social desirability, as participants were just as
      biased when reporting the taste estimates and willingness to pay anonymously
      (Experiment 3). Eco labels not only promote a willingness to pay more for the
      product but also lead to a more favorable perceptual experience of it. 

PMID- 24324624
TI  - Molecular evolution of threonine dehydratase in bacteria.
AB  - Threonine dehydratase converts L-threonine to 2-ketobutyrate. Several threonine
      dehydratases exist in bacteria, but their origins and evolutionary pathway are
      unknown. Here we analyzed all the available threonine dehydratases in bacteria
      and proposed an evolutionary pathway leading to the genes encoding three
      different threonine dehydratases CTD, BTD1 and BTD2. The ancestral threonine
      dehydratase might contain only a catalytic domain, but one or two ACT-like
      subdomains were fused during the evolution, resulting BTD1 and BTD2,
      respectively. Horizontal gene transfer, gene fusion, gene duplication, and gene
      deletion may occur during the evolution of this enzyme. The results are important
      for understanding the functions of various threonine dehydratases found in
      bacteria. 

PMID- 24324625
TI  - Glycation accelerates fibrillization of the amyloidogenic W7FW14F apomyoglobin.
AB  - Neurodegenerative diseases are associated with misfolding and deposition of
      specific proteins, either intra or extracellularly in the nervous system.
      Advanced glycation end products (AGEs) originate from different molecular species
      that become glycated after exposure to sugars. Several proteins implicated in
      neurodegenerative diseases have been found to be glycated in vivo and the extent
      of glycation is related to the pathologies of the patients. Although it is now
      accepted that there is a direct correlation between AGEs formation and the
      development of neurodegenerative diseases, several questions still remain
      unanswered: whether glycation is the triggering event or just an additional
      factor acting on the aggregation pathway. To this concern, in the present study
      we have investigated the effect of glycation on the aggregation pathway of the
      amyloidogenic W7FW14F apomyoglobin. Although this protein has not been related to
      any amyloid disease, it represents a good model to resemble proteins that
      intrinsically evolve toward the formation of amyloid aggregates in physiological
      conditions. We show that D-ribose, but not D-glucose, rapidly induces the W7FW14F
      apomyoglobin to generate AGEs in a time-dependent manner and protein ribosylation
      is likely to involve lysine residues on the polypeptide chain. Ribosylation of
      the W7FW14F apomyoglobin strongly affects its aggregation kinetics producing
      amyloid fibrils within few days. Cytotoxicity of the glycated aggregates has also
      been tested using a cell viability assay. We propose that ribosylation in the
      W7FW14F apomyoglobin induces the formation of a cross-link that strongly reduces
      the flexibility of the H helix and/or induce a conformational change that favor
      fibril formation. These results open new perspectives for AGEs biological role as
      they can be considered not only a triggering factor in amyloidosis but also a
      player in later stages of the aggregation process. 

PMID- 24324626
TI  - Response of bean (Vicia faba L.) plants to low sink demand by measuring the gas
      exchange rates and chlorophyll a fluorescence kinetics.
AB  - BACKGROUND: The decline of photosynthesis in plants under low sink demand is well
      known. Previous studies focused on the relationship between stomatal conductance
      (gs) and net photosynthetic rate (Pn). These studies investigated the effect of
      changes in Photosystem II (PSII) function on the Pn decline under low sink
      demand. However, little is known about its effects on different limiting steps of
      electron transport chain in PSII under this condition. METHODOLOGY/PRINCIPAL
      FINDING: Two-month-old bean plants were processed by removing pods and flowers
      (low sink demand). On the 1(st) day after low sink demand treatment, a decline of
      Pn was accompanied by a decrease in gs and internal-to-ambient CO2 concentration
      ratio (Ci/Ca). From the 3(rd) to 9(th) day, Pn and gs declined continuously while
      Ci/Ca ratio remained stable in the treatment. Moreover, these values were lower
      than that of control. Wk (a parameter reflecting the damage to oxygen evolving
      complex of the donor side of PSII) values in the treatment were significantly
      higher than their corresponding control values. However, RCQA (a parameter
      reflecting the number of active RCs per excited cross-section of PSII) values in
      the treatment were significantly lower than control from the 5(th) day. From the
      11(th) to 21(st) day, Pn and gs of the treatment continued to decline and were
      lower than control. This was accompanied by a decrease of RCQA, and an increase
      of Wk. Furthermore, the quantum yield parameters phiPo, phiEo and psiEo in the
      treatment were lower than in control; however, Ci/Ca values in the treatment
      gradually increased and were significantly higher than control on the 21(st) day.
      CONCLUSIONS: Stomatal limitation during the early stage, whereas a combination of
      stomatal and non-stomatal limitation during the middle stage might be responsible
      for the reduction of Pn under low sink demand. Non-stomatal limitation during the
      late stages after the removal of the sink of roots and pods may also cause Pn
      reduction. The non-stomatal limitation was associated with the inhibition of PSII
      electron transport chain. Our data suggests that the donor side of PSII was the
      most sensitive to low sink demand followed by the reaction center of PSII. The
      acceptor side of PSII may be the least sensitive.

PMID- 24324627
TI  - Djebelemur, a tiny pre-tooth-combed primate from the Eocene of Tunisia: a glimpse
      into the origin of crown strepsirhines.
AB  - BACKGROUND: Molecular clock estimates of crown strepsirhine origins generally
      advocate an ancient antiquity for Malagasy lemuriforms and Afro-Asian
      lorisiforms, near the onset of the Tertiary but most often extending back to the
      Late Cretaceous. Despite their inferred early origin, the subsequent evolutionary
      histories of both groups (except for the Malagasy aye-aye lineage) exhibit a
      vacuum of lineage diversification during most part of the Eocene, followed by a
      relative acceleration in diversification from the late Middle Eocene. This early
      evolutionary stasis was tentatively explained by the possibility of unrecorded
      lineage extinctions during the early Tertiary. However, this prevailing molecular
      view regarding the ancient origin and early diversification of crown
      strepsirhines must be viewed with skepticism due to the new but still scarce
      paleontological evidence gathered in recent years. METHODOLOGICAL/PRINCIPAL
      FINDINGS: Here, we describe new fossils attributable to Djebelemur martinezi,
      a~50 Ma primate from Tunisia (Djebel Chambi). This taxon was originally
      interpreted as a cercamoniine adapiform based on limited information from its
      lower dentition. The new fossils provide anatomical evidence demonstrating that
      Djebelemur was not an adapiform but clearly a distant relative of lemurs, lorises
      and galagos. Cranial, dental and postcranial remains indicate that this
      diminutive primate was likely nocturnal, predatory (primarily insectivorous), and
      engaged in a form of generalized arboreal quadrupedalism with frequent horizontal
      leaping. Djebelemur did not have an anterior lower dentition as specialized as
      that characterizing most crown strepsirhines (i.e., tooth-comb), but it clearly
      exhibited a transformed antemolar pattern representing an early stage of a crown
      strepsirhine-like adaptation ("pre-tooth-comb"). CONCLUSIONS/SIGNIFICANCE: These
      new fossil data suggest that the differentiation of the tooth-comb must postdate
      the djebelemurid divergence, a view which hence constrains the timing of crown
      strepsirhine origins to the Middle Eocene, and then precludes the existence of
      unrecorded lineage extinctions of tooth-combed primates during the earliest
      Tertiary.

PMID- 24324628
TI  - Spatial and feature-based attention in a layered cortical microcircuit model.
AB  - Directing attention to the spatial location or the distinguishing feature of a
      visual object modulates neuronal responses in the visual cortex and the stimulus
      discriminability of subjects. However, the spatial and feature-based modes of
      attention differently influence visual processing by changing the tuning
      properties of neurons. Intriguingly, neurons' tuning curves are modulated
      similarly across different visual areas under both these modes of attention.
      Here, we explored the mechanism underlying the effects of these two modes of
      visual attention on the orientation selectivity of visual cortical neurons. To do
      this, we developed a layered microcircuit model. This model describes multiple
      orientation-specific microcircuits sharing their receptive fields and consisting
      of layers 2/3, 4, 5, and 6. These microcircuits represent a functional grouping
      of cortical neurons and mutually interact via lateral inhibition and excitatory
      connections between groups with similar selectivity. The individual microcircuits
      receive bottom-up visual stimuli and top-down attention in different layers. A
      crucial assumption of the model is that feature-based attention activates
      orientation-specific microcircuits for the relevant feature selectively, whereas
      spatial attention activates all microcircuits homogeneously, irrespective of
      their orientation selectivity. Consequently, our model simultaneously accounts
      for the multiplicative scaling of neuronal responses in spatial attention and the
      additive modulations of orientation tuning curves in feature-based attention,
      which have been observed widely in various visual cortical areas. Simulations of
      the model predict contrasting differences between excitatory and inhibitory
      neurons in the two modes of attentional modulations. Furthermore, the model
      replicates the modulation of the psychophysical discriminability of visual
      stimuli in the presence of external noise. Our layered model with a biologically
      suggested laminar structure describes the basic circuit mechanism underlying the
      attention-mode specific modulations of neuronal responses and visual perception. 

PMID- 24324629
TI  - Silencing of DLGAP5 by siRNA significantly inhibits the proliferation and
      invasion of hepatocellular carcinoma cells.
AB  - BACKGROUND: The dysregulation of oncogenes and tumor suppressor genes plays an
      important role in many cancers, including hepatocellular carcinoma (HCC), which
      is one of the most common cancers in the world. In a previous microarray
      experiment, we found that DLGAP5 is overexpressed in HCCs. However, whether the
      up-regulation of DLGAP5 contributes to hepatocarcinogenesis remains unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we showed that DLGAP5 was
      significantly up-regulated in 76.4% (168 of 220) of the analyzed HCC specimens
      when compared with adjacent liver tissue. DLGAP5 overexpression was evident in
      25% (22 of 88) of the HCC specimens without AFP expression, suggesting that
      DLGAP5 may be a novel biomarker for HCC pathogenesis. The silencing of DLGAP5
      gene expression by RNA interference significantly suppressed cell growth,
      migration and colony formation in vitro. The expression level of DLGAP5 was also
      found to be related to the methylation level of its promoter in the HCC
      specimens. CONCLUSIONS/SIGNIFICANCE: Taken together, these data suggest that the
      expression of DLGAP5 is regulated by methylation and that the up-regulation of
      DLGAP5 contributes to HCC tumorigenesis by promoting cell proliferation.

PMID- 24324630
TI  - Automated characterization and parameter-free classification of cell tracks based
      on local migration behavior.
AB  - Cell migration is the driving force behind the dynamics of many diverse
      biological processes. Even though microscopy experiments are routinely performed
      today by which populations of cells are visualized in space and time, valuable
      information contained in image data is often disregarded because statistical
      analyses are performed at the level of cell populations rather than at the single
      cell level. Image-based systems biology is a modern approach that aims at
      quantitatively analyzing and modeling biological processes by developing novel
      strategies and tools for the interpretation of image data. In this study, we take
      first steps towards a fully automated characterization and parameter-free
      classification of cell track data that can be generally applied to tracked
      objects as obtained from image data. The requirements to achieve this aim
      include: (i) combination of different measures for single cell tracks, such as
      the confinement ratio and the asphericity of the track volume, and (ii)
      computation of these measures in a staggered fashion to retrieve local
      information from all possible combinations of track segments. We demonstrate for
      a population of synthetic cell tracks as well as for in vitro neutrophil tracks
      obtained from microscopy experiment that the information contained in the track
      data is fully exploited in this way and does not require any prior knowledge,
      which keeps the analysis unbiased and general. The identification of cells that
      show the same type of migration behavior within the population of all cells is
      achieved via agglomerative hierarchical clustering of cell tracks in the
      parameter space of the staggered measures. The recognition of characteristic
      patterns is highly desired to advance our knowledge about the dynamics of
      biological processes. 

PMID- 24324631
TI  - The evolutionary history and diverse physiological roles of the grapevine calcium
      dependent protein kinase gene family.
AB  - Calcium-dependent protein kinases (CDPKs) are molecular switches that bind
      Ca(2+), ATP, and protein substrates, acting as sensor relays and responders that
      convert Ca(2+) signals, created by developmental processes and environmental
      stresses, into phosphorylation events. The precise functions of the CDPKs in
      grapevine (Vitis vinifera) are largely unknown. We therefore investigated the
      phylogenetic relationships and expression profiles of the 17 CDPK genes
      identified in the 12x grapevine genome sequence, resolving them into four
      subfamilies based on phylogenetic tree topology and gene structures. The origins
      of the CDPKs during grapevine evolution were characterized, involving 13
      expansion events. Transcriptomic analysis using 54 tissues and developmental
      stages revealed three types of CDPK gene expression profiles: constitutive
      (housekeeping CDPKs), partitioned functions, and prevalent in pollen/stamen. We
      identified two duplicated CDPK genes that had evolved from housekeeping to pollen
      prevalent functions and whose origin correlated with that of seed plants,
      suggesting neofunctionalization with an important role in pollen development and
      also potential value in the breeding of seedless varieties. We also found that
      CDPKs were involved in three abiotic stress signaling pathways and could
      therefore be used to investigate the crosstalk between stress responses. 

PMID- 24324632
TI  - Bacterial endosymbiosis in a chordate host: long-term co-evolution and
      conservation of secondary metabolism.
AB  - Intracellular symbiosis is known to be widespread in insects, but there are few
      described examples in other types of host. These symbionts carry out useful
      activities such as synthesizing nutrients and conferring resistance against
      adverse events such as parasitism. Such symbionts persist through host speciation
      events, being passed down through vertical transmission. Due to various
      evolutionary forces, symbionts go through a process of genome reduction,
      eventually resulting in tiny genomes where only those genes essential to
      immediate survival and those beneficial to the host remain. In the marine
      environment, invertebrates such as tunicates are known to harbor complex
      microbiomes implicated in the production of natural products that are toxic and
      probably serve a defensive function. Here, we show that the intracellular
      symbiont Candidatus Endolissoclinum faulkneri is a long-standing symbiont of the
      tunicate Lissoclinum patella, that has persisted through cryptic speciation of
      the host. In contrast to the known examples of insect symbionts, which tend to be
      either relatively recent or ancient relationships, the genome of Ca. E. faulkneri
      has a very low coding density but very few recognizable pseudogenes. The almost
      complete degradation of intergenic regions and stable gene inventory of extant
      strains of Ca. E. faulkneri show that further degradation and deletion is
      happening very slowly. This is a novel stage of genome reduction and provides
      insight into how tiny genomes are formed. The ptz pathway, which produces the
      defensive patellazoles, is shown to date to before the divergence of Ca. E.
      faulkneri strains, reinforcing its importance in this symbiotic relationship.
      Lastly, as in insects we show that stable symbionts can be lost, as we describe
      an L. patella animal where Ca. E. faulkneri is displaced by a likely
      intracellular pathogen. Our results suggest that intracellular symbionts may be
      an important source of ecologically significant natural products in animals. 

PMID- 24324633
TI  - Variable effects of dispersal on productivity of bacterial communities due to
      changes in functional trait composition.
AB  - Previous studies have shown variable relationships between dispersal rate and
      ecosystem functioning, but the reasons for and mechanisms behind variable
      dispersal rate-functioning patterns are currently unknown. In this study we used
      six bacterial lake water communities in a laboratory experiment in order to
      investigate how dispersal among communities influences community productivity by
      evaluating three different mechanisms: 1) changes in taxonomic diversity, 2)
      changes in phylogenetic diversity or 3) changes in the composition of functional
      traits. The experiment was conducted in two phases; (A) a dialysis bag experiment
      where the dispersal rate among six communities was manipulated and the subsequent
      change in bacterial diversity and growth rate was recorded, and (B) a regrowth
      experiment where we manipulated available resources to study how well a taxon
      grows on certain organic carbon resources, i.e. their functional traits. From
      experiment (B) we could thus estimate changes in functional traits in communities
      in experiment (A). Bacterial production was affected by dispersal, but not
      consistently among lakes. Neither change in taxonomic or phylogenetic diversity
      with dispersal could explain the observed dispersal-productivity relationships.
      Instead, changes in trait composition with dispersal, especially the communities'
      ability to use p-coumaric acid, an aromatic compound, could explain the observed
      dispersal-productivity relationships. Changes in this trait caused by dispersal
      seemed especially important for bacterial productivity in waters with a high
      aromaticity of the organic matter pool. We conclude that the effect of dispersal
      on bacterial communities can affect ecosystem functioning in different ways,
      through changes in functional key-traits which are important for the local
      environment.

PMID- 24324634
TI  - Machine learning for automatic prediction of the quality of electrophysiological
      recordings.
AB  - The quality of electrophysiological recordings varies a lot due to technical and
      biological variability and neuroscientists inevitably have to select "good"
      recordings for further analyses. This procedure is time-consuming and prone to
      selection biases. Here, we investigate replacing human decisions by a machine
      learning approach. We define 16 features, such as spike height and width, select
      the most informative ones using a wrapper method and train a classifier to
      reproduce the judgement of one of our expert electrophysiologists. Generalisation
      performance is then assessed on unseen data, classified by the same or by another
      expert. We observe that the learning machine can be equally, if not more,
      consistent in its judgements as individual experts amongst each other. Best
      performance is achieved for a limited number of informative features; the optimal
      feature set being different from one data set to another. With 80-90% of correct
      judgements, the performance of the system is very promising within the data sets
      of each expert but judgments are less reliable when it is used across sets of
      recordings from different experts. We conclude that the proposed approach is
      relevant to the selection of electrophysiological recordings, provided parameters
      are adjusted to different types of experiments and to individual experimenters. 

PMID- 24324635
TI  - 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without
      compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.
AB  - BACKGROUND/AIMS: Nephrotoxicity is a frequent and major limitation in cisplatin
      (CDDP)-based chemotherapy. 5-Aminolevulinic acid (ALA) is widely distributed in
      animal cells, and it is a precursor of tetrapyrole compounds such as heme that is
      fundamentally important in aerobic energy metabolism. The aim of this study is to
      evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI).
      METHOD: We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK
      52E). We divided four groups of rats: control, CDDP only, CDDP + ALA(post);(ALA
      10 mg/kg + Fe in drinking water) after CDDP, CDDP + ALA(pre & post). RESULT: CDDP
      increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced
      these changes. ALA ameliorates CDDP-induced morphological renal damages, and
      reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3.
      Protein and mRNA levels of ATP5alpha, complex(COX) IV, UCP2, PGC-1alpha in renal
      tissue were significantly decreased by CDDP, and ALA ameliorates reduction of
      these enzymes. In contrast, Heme Oxigenase (HO)-1 level is induced by CDDP
      treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells,
      the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes
      was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated
      by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated
      bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects
      of CDDP. CONCLUSION: These data suggested that the protective role of ALA in
      cisplatin-induced AKI is via protection of mitochondrial viability and prevents
      tubular apoptosis. Also there are no significant effects of ALA on anticancer
      efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP
      nephrotoxicity without compromising its anticancer efficacy.

PMID- 24324636
TI  - Cross-species extrapolation of prediction models for cadmium transfer from soil
      to corn grain.
AB  - Cadmium (Cd) is a highly toxic heavy metal for both plants and animals. The
      presence of Cd in agricultural soils is of great concern regarding its transfer
      in the soil-plant system. This study investigated the transfer of Cd (exogenous
      salts) from a wide range of Chinese soils to corn grain (Zhengdan 958). Through
      multiple stepwise regressions, prediction models were developed, with the
      combination of Cd bioconcentration factor (BCF) of Zhengdan 958 and soil pH,
      organic matter (OM) content, and cation exchange capacity (CEC). Moreover, these
      prediction models from Zhengdan 958 were applied to other non-model corn species
      through cross-species extrapolation approach. The results showed that the pH of
      the soil was the most important factor that controlled Cd uptake and lower pH was
      more favorable for Cd bioaccumulation in corn grain. There was no significant
      difference among three prediction models in the different Cd levels. When the
      prediction models were applied to other non-model corn species, the ratio ranges
      between the predicted BCF values and the measured BCF values were within an
      interval of 2 folds and close to the solid line of 1?1 relationship. Furthermore,
      these prediction models also reduced the measured BCF intra-species variability
      for all non-model corn species. Therefore, the prediction models established in
      this study can be applied to other non-model corn species and be useful for
      predicting the Cd bioconcentration in corn grain and assessing the ecological
      risk of Cd in different soils. 

PMID- 24324637
TI  - Protective effect of ginsenoside Rb1 against intestinal ischemia-reperfusion
      induced acute renal injury in mice.
AB  - Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng,
      possesses a variety of biological activities. The objectives of this study were
      to investigate the protective effects of RB1 and its underlying mechanism on
      renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was
      administered prior to inducing IIR achieved by occluding the superior mesenteric
      artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid
      (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult
      male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR
      group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 +
      ATRA group. Intestinal histology and pathological injury score were observed.
      Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase
      (DAO). Renal injury induced by IIR was characterized by increased levels of
      histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr)
      and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with
      elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1
      significantly reduced renal injury and apoptosis as compared with IIR group,
      which was reversed by ATRA treatment. Immunohistochemistry and Western blot
      analysis demonstrated that RB1 significantly upregulated the protein expression
      of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment.
      Taken together, these results suggest that the protective effects of RB1
      pretreatment against renal injury induced by IIR are associated with activation
      of the Nrf2/ anti-oxidant response element (ARE) pathway. 

PMID- 24324638
TI  - The kinetics of G2 and M transitions regulated by B cyclins.
AB  - B cyclins regulate G2-M transition. Because human somatic cells continue to cycle
      after reduction of cyclin B1 (cycB1) or cyclin B2 (cycB2) by RNA interference
      (RNAi), and because cycB2 knockout mice are viable, the existence of two genes
      should be an optimization. To explore this idea, we generated HeLa BDTM Tet-Off
      cell lines with inducible cyclin B1- or B2-EGFP that were RNAi resistant.
      Cultures were treated with RNAi and/or doxycycline (Dox) and bromodeoxyuridine.
      We measured G2 and M transit times and 4C cell accumulation. In the absence of
      ectopic B cyclin expression, knockdown (kd) of either cyclin increased G2
      transit. M transit was increased by cycB1 kd but decreased by cycB2 depletion.
      This novel difference was further supported by time-lapse microscopy. This
      suggests that cycB2 tunes mitotic timing, and we speculate that this is through
      regulation of a Golgi checkpoint. In the presence of endogenous cyclins,
      expression of active B cyclin-EGFPs did not affect G2 or M phase times. As
      previously shown, B cyclin co-depletion induced G2 arrest. Expression of either B
      cyclin-EGFP completely rescued knockdown of the respective endogenous cyclin in
      single kd experiments, and either cyclin-EGFP completely rescued endogenous
      cyclin co-depletion. Most of the rescue occurred at relatively low levels of
      exogenous cyclin expression. Therefore, cycB1 and cycB2 are interchangeable for
      ability to promote G2 and M transition in this experimental setting. Cyclin B1 is
      thought to be required for the mammalian somatic cell cycle, while cyclin B2 is
      thought to be dispensable. However, residual levels of cyclin B1 or cyclin B2 in
      double knockdown experiments are not sufficient to promote successful mitosis,
      yet residual levels are sufficient to promote mitosis in the presence of the
      dispensible cyclin B2. We discuss a simple model that would explain most data if
      cyclin B1 is necessary. 

PMID- 24324639
TI  - Long-term impact of preterm birth on exercise capacity in healthy young men: a
      national population-based cohort study.
AB  - BACKGROUND: Increasing numbers of survivors of preterm birth are growing into
      adulthood today. Long-term health-effects of prematurity are still poorly
      understood, but include increased risk for diabetes, obesity and cardiovascular
      diseases in adult life. To test if reduced physical fitness may be a link in the
      causal chain of preterm birth and diseases in later life, the association of
      preterm birth and adult exercise capacity was investigated. The hypothesis was
      that preterm birth contributes independently of other risk factors to lower
      physical fitness in adulthood. METHODS AND FINDINGS: Population-based national
      cohort study of all males conscripting for military service in 1993-2001 and born
      in Sweden 1973-1983, n = 218,820. Data were retrieved from the Swedish Conscript
      Register, the Medical Birth Register and the Population and Housing Census 1990.
      Primary outcome was the results from maximal exercise test (Wmax in Watt)
      performed at conscription. Association to perinatal and socioeconomic risk
      factors, other co-variates and confounders were analysed. General linear
      modelling showed that preterm birth predicted low Wmax in a dose-response related
      pattern, with 25 Watt reduction in Wmax for the lowest gestational ages, those
      born <=27 weeks. Low birth weight for gestational age also independently
      predicted low Wmax compared to normal and high birth weight (32 Watt reduction
      for those with a birth weight Standard Deviation Score <2). Low parental
      education was significantly associated with reduced Wmax (range 17 Watt), as well
      as both low and high current BMI, with severe obesity resulting in a 16 Watt
      deficit compared to Wmax top performance. CONCLUSION: Being born preterm as well
      as being born small for gestational age predicts low exercise capacity in
      otherwise healthy young men. The effect size of being born preterm equal or
      exceed that of other known risk factors for unfitness in adults, such as low
      parental education and overweight.

PMID- 24324640
TI  - Factors that affect proliferation of Salmonella in tomatoes post-harvest: the
      roles of seasonal effects, irrigation regime, crop and pathogen genotype.
AB  - MAIN OBJECTIVES: Fresh fruits and vegetables become increasingly recognized as
      vehicles of human salmonellosis. Physiological, ecological, and environmental
      factors are all thought to contribute to the ability of Salmonella to colonize
      fruits and vegetables pre- and post-harvest. The goal of this study was to test
      how irrigation levels, fruit water congestion, crop and pathogen genotypes affect
      the ability of Salmonella to multiply in tomatoes post-harvest. EXPERIMENTAL
      DESIGN: Fruits from three tomato varieties, grown over three production seasons
      in two Florida locations, were infected with seven strains of Salmonella and
      their ability to multiply post-harvest in field-grown tomatoes was tested. The
      field experiments were set up as a two-factor factorial split plot experiment,
      with the whole-plot treatments arranged in a randomized complete-block design.
      The irrigation treatment (at three levels) was the whole-plot factor, and the
      split-plot factor was tomato variety, with three levels. The significance of the
      main, two-way, and three-way interaction effects was tested using the (type III)
      F-tests for fixed effects. Mean separation for each significant fixed effect in
      the model was performed using Tukey's multiple comparison testing procedure. MOST
      IMPORTANT DISCOVERIES AND SIGNIFICANCE: The irrigation regime per se did not
      affect susceptibility of the crop to post-harvest proliferation of Salmonella.
      However, Salmonella grew significantly better in water-congested tissues of green
      tomatoes. Tomato maturity and genotype, Salmonella genotype, and inter-seasonal
      differences were the strongest factors affecting proliferation. Red ripe tomatoes
      were significantly and consistently more conducive to proliferation of
      Salmonella. Tomatoes harvested in the driest, sunniest season were the most
      conducive to post-harvest proliferation of the pathogen. Statistically
      significant interactions between production conditions affected post-harvest
      susceptibility of the crop to the pathogen. UV irradiation of tomatoes post
      harvest promoted Salmonella growth.

PMID- 24324641
TI  - Acteoside suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos
      induction and NF-kappaB pathway and attenuating ROS production.
AB  - Numerous studies have reported that inflammatory cytokines are important
      mediators for osteoclastogenesis, thereby causing excessive bone resorption and
      osteoporosis. Acteoside, the main active compound of Rehmannia glutinosa, which
      is used widely in traditional Oriental medicine, has anti-inflammatory and
      antioxidant potentials. In this study, we found that acteoside markedly inhibited
      osteoclast differentiation and formation from bone marrow macrophages (BMMs) and
      RAW264.7 macrophages stimulated by the receptor activator of nuclear factor
      kappaB (NF-kappaB) ligand (RANKL). Acteoside pretreatment also prevented bone
      resorption by mature osteoclasts in a dose-dependent manner. Acteoside (10 uM)
      attenuated RANKL-stimulated activation of p38 kinase, extracellular signal
      regulated kinases, and c-Jun N-terminal kinase, and also suppressed NF-kappaB
      activation by inhibiting phosphorylation of the p65 subunit and the inhibitor
      kappaBalpha. In addition, RANKL-mediated increases in the expression of c-Fos and
      nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and in the production
      of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 were apparently
      inhibited by acteoside pretreatment. Further, oral acteoside reduced ovariectomy
      induced bone loss and inflammatory cytokine production to control levels. Our
      data suggest that acteoside inhibits osteoclast differentiation and maturation
      from osteoclastic precursors by suppressing RANKL-induced activation of mitogen
      activated protein kinases and transcription factors such as NF-kappaB, c-Fos, and
      NFATc1. Collectively, these results suggest that acteoside may act as an anti
      resorptive agent to reduce bone loss by blocking osteoclast activation. 

PMID- 24324642
TI  - The development of upper limb movements: from fetal to post-natal life.
AB  - BACKGROUND: The aim of this longitudinal study was to investigate how the
      kinematic organization of upper limb movements changes from fetal to post-natal
      life. By means of off-line kinematical techniques we compared the kinematics of
      hand-to-mouth and hand-to-eye movements, in the same individuals, during prenatal
      life and early postnatal life, as well as the kinematics of hand-to-mouth and
      reaching-toward-object movements in the later age periods. METHODOLOGY/PRINCIPAL
      FINDINGS: Movements recorded at the 14(th), 18(th) and 22(nd) week of gestation
      were compared with similar movements recorded in an ecological context at 1, 2,
      3, 4, 8, and 12 months after birth. The results indicate a similar kinematic
      organization depending on movement type (i.e., eye, mouth) for the infants at one
      month and for the fetuses at 22 weeks of gestation. At two and three months such
      differential motor planning depending on target is lost and no statistical
      differences emerge. Hand to eye movements were no longer observed after the
      fourth month of life, therefore we compared kinematics for hand to mouth with
      hand to object movements. Results of these analyses revealed differences in the
      performance of hand to mouth and reaching to object movements in the length of
      the deceleration phase of the movement, depending on target.
      CONCLUSION/SIGNIFICANCE: Data are discussed in terms of how the passage from
      intrauterine to extra-uterine environments modifies motor planning. These results
      provide novel evidence of how different types of upper extremity movements, those
      directed towards one's own face and those directed to external objects, develop.

PMID- 24324643
TI  - Task dependency of grip stiffness--a study of human grip force and grip stiffness
      dependency during two different tasks with same grip forces.
AB  - It is widely known that the pinch-grip forces of the human hand are linearly
      related to the weight of the grasped object. Less is known about the relationship
      between grip force and grip stiffness. We set out to determine variations to
      these dependencies in different tasks with and without visual feedback. In two
      different settings, subjects were asked to (a) grasp and hold a stiffness
      measuring manipulandum with a predefined grip force, differing from experiment to
      experiment, or (b) grasp and hold this manipulandum of which we varied the weight
      between trials in a more natural task. Both situations led to grip forces in
      comparable ranges. As the measured grip stiffness is the result of muscle and
      tendon properties, and since muscle/tendon stiffness increases more-or-less
      linearly as a function of muscle force, we found, as might be predicted, a linear
      relationship between grip force and grip stiffness. However, the measured
      stiffness ranges and the increase of stiffness with grip force varied
      significantly between the two tasks. Furthermore, we found a strong correlation
      between regression slope and mean stiffness for the force task which we ascribe
      to a force stiffness curve going through the origin. Based on a biomechanical
      model, we attributed the difference between both tasks to changes in wrist
      configuration, rather than to changes in cocontraction. In a new set of
      experiments where we prevent the wrist from moving by fixing it and resting it on
      a pedestal, we found subjects exhibiting similar stiffness/force characteristics
      in both tasks. 

PMID- 24324644
TI  - Bisphosphonates for the prevention and treatment of osteoporosis in patients with
      rheumatic diseases: a systematic review and meta-analysis.
AB  - BACKGROUND: While bisphosphonates (BPs) are commonly used in clinical treatment
      for osteoporosis, their roles on osteoporosis treatment for rheumatic patients
      remain unclear. We performed a meta-analysis to evaluate the efficacy of BPs on
      fractures prevention and bone mass preserving in rheumatic patients.
      METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, EmBase, and the Cochrane
      Central Register of Controlled Trials for relevant literatures with a time limit
      of Jan. 6, 2012. All randomized clinical trials of BPs for adult rheumatic
      patients with a follow-up of 6 months or more were included. We calculated
      relative risks (RRs) for fractures and weighted mean difference (WMD) for percent
      change of bone mineral density (BMD). Twenty trials were included for analysis.
      The RR in rheumatic patients treated with BPs was 0.61 (95%CI [0.44, 0.83], P =
      0.002) for vertebral fractures, and 0.49 (95%CI [0.23, 1.02], P = 0.06) for non
      vertebral fractures. The WMD of BMD change in the lumbar spine was 3.72% (95%CI
      [2.72, 4.72], P<0.001) at 6 months, 3.67% (95%CI [2.84, 4.50], P<0.001) at 12
      months, 3.64% (95%CI [2.59, 4.69], P<0.001) at 24 months, and 5.87% (95%CI [4.59,
      7.15], P<0.001) at 36 months in patients using BPs, as compared with those
      treated with calcium, vitamin D or calcitonin. In subgroup analyses, rheumatic
      patients using BPs for osteoporosis prevention had greater WMD than those using
      BPs for treating osteoporosis at 6 months (4.53% vs. 2.73%, P = 0.05) and 12
      months (4.93% vs. 2.91%, P = 0.01). CONCLUSIONS/SIGNIFICANCE: In both short-term
      and middle-term, BPs can preserve bone mass and reduce the incidence of vertebral
      fractures in rheumatic patients, mainly for those who have GC consumption. The
      efficacy of BPs is better when using BPs to prevent rather than to treat
      osteoporosis in rheumatic patients.

PMID- 24324646
TI  - In-line phase contrast imaging of hepatic portal vein embolization with
      radiolucent embolic agents in mice: a preliminary study.
AB  - It is crucial to understand the distribution of embolic agents inside target
      liver during and after the hepatic portal vein embolization (PVE) procedure. For
      a long time, the problem has not been well solved due to the radiolucency of
      embolic agents and the resolution limitation of conventional radiography. In this
      study, we first reported use of fluorescent carboxyl microspheres (FCM) as
      radiolucent embolic agents for embolizing hepatic portal veins. The fluorescent
      characteristic of FCM could help to determine their approximate location easily.
      Additionally, the microspheres were found to be fairly good embolizing agents for
      PVE. After the livers were excised and fixed, they were imaged by in-line phase
      contrast imaging (PCI), which greatly improved the detection of the radiolucent
      embolic agents as compared to absorption contrast imaging (ACI). The preliminary
      study has for the first time shown that PCI has great potential in the pre
      clinical investigation of PVE with radiolucent embolic agents. 

PMID- 24324645
TI  - A model of an integrated immune system pathway in Homo sapiens and its
      interaction with superantigen producing expression regulatory pathway in
      Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed
      pathway.
AB  - Response of an immune system to a pathogen attack depends on the balance between
      the host immune defense and the virulence of the pathogen. Investigation of
      molecular interactions between the proteins of a host and a pathogen helps in
      identifying the pathogenic proteins. It is necessary to understand the dynamics
      of a normally behaved host system to evaluate the capacity of its immune system
      upon pathogen attack. In this study, we have compared the behavior of an
      unperturbed and pathogen perturbed host system. Moreover, we have developed a
      formalism under Flux Balance Analysis (FBA) for the optimization of conflicting
      objective functions. We have constructed an integrated pathway system, which
      includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR
      signaling pathway of Homo sapiens. We have implemented the method on this pathway
      system and observed the behavior of host signaling molecules upon pathogen
      attack. The entire study has been divided into six different cases, based on the
      perturbed/unperturbed conditions. In other words, we have investigated
      unperturbed and pathogen perturbed human TCR signaling pathway, with different
      combinations of optimization of concentrations of regulatory and signaling
      molecules. One of these cases has aimed at finding out whether minimization of
      the toxin production in a pathogen leads to the change in the concentration
      levels of the proteins coded by TCR signaling pathway genes in the infected host.
      Based on the computed results, we have hypothesized that the balance between TCR
      signaling inhibitory and stimulatory molecules can keep TCR signaling system into
      resting/stimulating state, depending upon the perturbation. The proposed
      integrated host-pathogen interaction pathway model has accurately reflected the
      experimental evidences, which we have used for validation purpose. The
      significance of this kind of investigation lies in revealing the susceptible
      interaction points that can take back the Staphylococcal Enterotoxin (SE)
      challenged system within the range of normal behavior. 

PMID- 24324647
TI  - Astrocytes directly influence tumor cell invasion and metastasis in vivo.
AB  - Brain metastasis is a defining component of tumor pathophysiology, and the
      underlying mechanisms responsible for this phenomenon are not well understood.
      Current dogma is that tumor cells stimulate and activate astrocytes, and this
      mutual relationship is critical for tumor cell sustenance in the brain. Here, we
      provide evidence that primary rat neonatal and adult astrocytes secrete factors
      that proactively induced human lung and breast tumor cell invasion and metastasis
      capabilities. Among which, tumor invasion factors namely matrix metalloprotease-2
      (MMP-2) and MMP-9 were partly responsible for the astrocyte media-induced tumor
      cell invasion. Inhibiting MMPs reduced the ability of tumor cell to migrate and
      invade in vitro. Further, injection of astrocyte media-conditioned breast cancer
      cells in mice showed increased invasive activity to the brain and other distant
      sites. More importantly, blocking the preconditioned tumor cells with broad
      spectrum MMP inhibitor decreased the invasion and metastasis of the tumor cells,
      in particular to the brain in vivo. Collectively, our data implicate astrocyte
      derived MMP-2 and MMP-9 as critical players that facilitate tumor cell migration
      and invasion leading to brain metastasis. 

PMID- 24324648
TI  - Genome-wide association study for levels of total serum IgE identifies HLA-C in a
      Japanese population.
AB  - Most of the previously reported loci for total immunoglobulin E (IgE) levels are
      related to Th2 cell-dependent pathways. We undertook a genome-wide association
      study (GWAS) to identify genetic loci responsible for IgE regulation. A total of
      479,940 single nucleotide polymorphisms (SNPs) were tested for association with
      total serum IgE levels in 1180 Japanese adults. Fine-mapping with SNP imputation
      demonstrated 6 candidate regions: the PYHIN1/IFI16, MHC classes I and II, LEMD2,
      GRAMD1B, and chr13?60576338 regions. Replication of these candidate loci in each
      region was assessed in 2 independent Japanese cohorts (n = 1110 and 1364,
      respectively). SNP rs3130941 in the HLA-C region was consistently associated with
      total IgE levels in 3 independent populations, and the meta-analysis yielded
      genome-wide significance (P = 1.07*10(-10)). Using our GWAS results, we also
      assessed the reproducibility of previously reported gene associations with total
      IgE levels. Nine of 32 candidate genes identified by a literature search were
      associated with total IgE levels after correction for multiple testing. Our
      findings demonstrate that SNPs in the HLA-C region are strongly associated with
      total serum IgE levels in the Japanese population and that some of the previously
      reported genetic associations are replicated across ethnic groups. 

PMID- 24324649
TI  - Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup repeat
      specificity.
AB  - Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential
      anti-cancer drug target implicated in several cellular functions. We have used
      protein crystallography to solve crystal structures of the human G3BP1 NTF2-like
      domain both alone and in complex with an FxFG Nup repeat peptide. Despite high
      structural similarity, the FxFG binding site is located between two alpha helices
      in the G3BP1 NTF2-like domain and not at the dimer interface as observed for
      nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif
      but not FG and GLFG motifs. The unliganded form of the G3BP1 NTF2-like domain was
      solved in two crystal forms to resolutions of 1.6 and 3.3 A in space groups
      P212121 and P6322 based on two different constructs, residues 1-139 and 11-139,
      respectively. Crystal packing of the N-terminal residues against a symmetry
      related molecule in the P212121 crystal form might indicate a novel ligand
      binding site that, however, remains to be validated. The crystal structures give
      insight into the nuclear transportation mechanisms of G3BP and provide a basis
      for future structure based drug design. 

PMID- 24324650
TI  - Evolution of the global use of unsafe medical injections, 2000-2010.
AB  - OBJECTIVE: Since 1999, substantial efforts have been made by the international
      community to reduce the risks associated with unsafe injections, through
      ministries of health, international donors, the World Health Organization and the
      Safe Injection Global Network. The present study attempted to measure the
      progress, or lack thereof, made over the 2000-2010 decade in reducing unsafe
      injections in ten regions of the world corresponding to developing and
      transitional economies. METHODS: Data about the number of injections per person
      per year and the proportion of re-use of syringes and needles were obtained for
      2010, mainly from population surveys, and compared with previous estimates for
      2000 which had used various sources of information including injection safety
      assessments, population surveys and published studies on injection practices.
      RESULTS: From 2000 to 2010, in developing countries and transitional economies,
      the average number of injections per person per year decreased from 3.40 to 2.88,
      while the proportion of re-use of injection devices dropped from 39.8% to 5.5%.
      Combining both factors the number of unsafe injections per person per year
      decreased from 1.35 to 0.16. Even if substantial progress has been made, the
      Eastern Mediterranean region remains problematic, with 0.57 unsafe injections per
      person per year. In sub-Saharan Africa and Latin America, people now receive on
      average only 0.04-0.05 unsafe injections per year. CONCLUSION: Substantial
      progress has been made in reducing the number of unsafe injections in developing
      countries and transitional economies, essentially through a reduction in the re
      use of injection devices. In some regions, elimination of unsafe injections might
      become a reasonable goal.

PMID- 24324651
TI  - Looking like a leader-facial shape predicts perceived height and leadership
      ability.
AB  - Judgments of leadership ability from face images predict the outcomes of actual
      political elections and are correlated with leadership success in the corporate
      world. The specific facial cues that people use to judge leadership remain
      unclear, however. Physical height is also associated with political and
      organizational success, raising the possibility that facial cues of height
      contribute to leadership perceptions. Consequently, we assessed whether cues to
      height exist in the face and, if so, whether they are associated with perception
      of leadership ability. We found that facial cues to perceived height had a strong
      relationship with perceived leadership ability. Furthermore, when allowed to
      manually manipulate faces, participants increased facial cues associated with
      perceived height in order to maximize leadership perception. A morphometric
      analysis of face shape revealed that structural facial masculinity was not
      responsible for the relationship between perceived height and perceived
      leadership ability. Given the prominence of facial appearance in making social
      judgments, facial cues to perceived height may have a significant influence on
      leadership selection. 

PMID- 24324652
TI  - De novo assembly of the transcriptome of the non-model plant Streptocarpus rexii
      employing a novel heuristic to recover locus-specific transcript clusters.
AB  - De novo transcriptome characterization from Next Generation Sequencing data has
      become an important approach in the study of non-model plants. Despite notable
      advances in the assembly of short reads, the clustering of transcripts into
      unigene-like (locus-specific) clusters remains a somewhat neglected subject.
      Indeed, closely related paralogous transcripts are often merged into single
      clusters by current approaches. Here, a novel heuristic method for locus-specific
      clustering is compared to that implemented in the de novo assembler Oases, using
      the same initial transcript collections, derived from Arabidopsis thaliana and
      the developmental model Streptocarpus rexii. We show that the proposed approach
      improves cluster specificity in the A. thaliana dataset for which the reference
      genome is available. Furthermore, for the S. rexii data our filtered transcript
      collection matches a larger number of distinct annotated loci in reference
      genomes than the Oases set, while containing a reduced overall number of loci. A
      detailed discussion of advantages and limitations of our approach in processing
      de novo transcriptome reconstructions is presented. The proposed method should be
      widely applicable to other organisms, irrespective of the transcript assembly
      method employed. The S. rexii transcriptome is available as a sophisticated and
      augmented publicly available online database. 

PMID- 24324653
TI  - Bringing dicynodonts back to life: paleobiology and anatomy of a new emydopoid
      genus from the Upper Permian of Mozambique.
AB  - Dicynodontia represent the most diverse tetrapod group during the Late Permian.
      They survived the Permo-Triassic extinction and are central to understanding
      Permo-Triassic terrestrial ecosystems. Although extensively studied, several
      aspects of dicynodont paleobiology such as, neuroanatomy, inner ear morphology
      and internal cranial anatomy remain obscure. Here we describe a new dicynodont
      (Therapsida, Anomodontia) from northern Mozambique: Niassodon mfumukasi gen. et
      sp. nov. The holotype ML1620 was collected from the Late Permian K5 formation,
      Metangula Graben, Niassa Province northern Mozambique, an almost completely
      unexplored basin and country for vertebrate paleontology. Synchrotron radiation
      based micro-computed tomography (SRuCT), combined with a phylogenetic analysis,
      demonstrates a set of characters shared with Emydopoidea. All individual bones
      were digitally segmented allowing a 3D visualization of each element. In
      addition, we reconstructed the osseous labyrinth, endocast, cranial nerves and
      vasculature. The brain is narrow and the cerebellum is broader than the
      forebrain, resembling the conservative, "reptilian-grade" morphology of other non
      mammalian therapsids, but the enlarged paraflocculi occupy the same relative
      volume as in birds. The orientation of the horizontal semicircular canals
      indicates a slightly more dorsally tilted head posture than previously assumed in
      other dicynodonts. In addition, synchrotron data shows a secondary center of
      ossification in the femur. Thus ML1620 represents, to our knowledge, the oldest
      fossil evidence of a secondary center of ossification, pushing back the
      evolutionary origins of this feature. The fact that the specimen represents a new
      species indicates that the Late Permian tetrapod fauna of east Africa is still
      incompletely known. 

PMID- 24324654
TI  - Health insurance utilization and its impact: observations from the middle-aged
      and elderly in China.
AB  - OBJECTIVE: In China, despite a high coverage rate, health insurance is not used
      for all illness episodes. Our goal is to identify subjects' characteristics
      associated with insurance utilization and the association between utilization and
      medical expenditure. METHODS: A survey was conducted in January and February of
      2012. 2093 middle-aged and elderly subjects (45 years old and above) were
      surveyed. RESULTS: Heath insurance was not utilized for 12.6% (inpatient), 53.3%
      (outpatient), and 72.6% (self-treatment) of disease episodes. Subjects'
      characteristics were associated with insurance utilization. Inpatient and
      outpatient treatments were expensive. In the multivariate analysis of outpatient
      treatment expenditure, insurance utilization was significantly associated with
      higher treatment cost, lost income, and gross total cost. CONCLUSION: Utilization
      of health insurance may need to be improved. Insurance utilization can reduce out
      of-pocket medical expenditure. However, the amount paid by the insured is still
      high. Policy intervention is needed to further improve the effectiveness of
      health insurance.

PMID- 24324655
TI  - Using satellite and airborne LiDAR to model woodpecker habitat occupancy at the
      landscape scale.
AB  - Incorporating vertical vegetation structure into models of animal distributions
      can improve understanding of the patterns and processes governing habitat
      selection. LiDAR can provide such structural information, but these data are
      typically collected via aircraft and thus are limited in spatial extent. Our
      objective was to explore the utility of satellite-based LiDAR data from the
      Geoscience Laser Altimeter System (GLAS) relative to airborne-based LiDAR to
      model the north Idaho breeding distribution of a forest-dependent ecosystem
      engineer, the Red-naped sapsucker (Sphyrapicus nuchalis). GLAS data occurred
      within ca. 64 m diameter ellipses spaced a minimum of 172 m apart, and all
      occupancy analyses were confined to this grain scale. Using a hierarchical
      approach, we modeled Red-naped sapsucker occupancy as a function of LiDAR metrics
      derived from both platforms. Occupancy models based on satellite data were weak,
      possibly because the data within the GLAS ellipse did not fully represent habitat
      characteristics important for this species. The most important structural
      variables influencing Red-naped Sapsucker breeding site selection based on
      airborne LiDAR data included foliage height diversity, the distance between major
      strata in the canopy vertical profile, and the vegetation density near the
      ground. These characteristics are consistent with the diversity of foraging
      activities exhibited by this species. To our knowledge, this study represents the
      first to examine the utility of satellite-based LiDAR to model animal
      distributions. The large area of each GLAS ellipse and the non-contiguous nature
      of GLAS data may pose significant challenges for wildlife distribution modeling;
      nevertheless these data can provide useful information on ecosystem vertical
      structure, particularly in areas of gentle terrain. Additional work is thus
      warranted to utilize LiDAR datasets collected from both airborne and past and
      future satellite platforms (e.g. GLAS, and the planned IceSAT2 mission) with the
      goal of improving wildlife modeling for more locations across the globe. 

PMID- 24324656
TI  - Decoding humor experiences from brain activity of people viewing comedy movies.
AB  - Humans naturally have a sense of humor. Experiencing humor not only encourages
      social interactions, but also produces positive physiological effects on the
      human body, such as lowering blood pressure. Recent neuro-imaging studies have
      shown evidence for distinct mental state changes at work in people experiencing
      humor. However, the temporal characteristics of these changes remain elusive. In
      this paper, we objectively measured humor-related mental states from single-trial
      functional magnetic resonance imaging (fMRI) data obtained while subjects viewed
      comedy TV programs. Measured fMRI data were labeled on the basis of the lag
      before or after the viewer's perception of humor (humor onset) determined by the
      viewer-reported humor experiences during the fMRI scans. We trained multiple
      binary classifiers, or decoders, to distinguish between fMRI data obtained at
      each lag from ones obtained during a neutral state in which subjects were not
      experiencing humor. As a result, in the right dorsolateral prefrontal cortex and
      the right temporal area, the decoders showed significant classification
      accuracies even at two seconds ahead of the humor onsets. Furthermore, given a
      time series of fMRI data obtained during movie viewing, we found that the
      decoders with significant performance were also able to predict the upcoming
      humor events on a volume-by-volume basis. Taking into account the hemodynamic
      delay, our results suggest that the upcoming humor events are encoded in specific
      brain areas up to about five seconds before the awareness of experiencing humor.
      Our results provide evidence that there exists a mental state lasting for a few
      seconds before actual humor perception, as if a viewer is expecting the future
      humorous events. 

PMID- 24324657
TI  - A new saurichthyiform (Actinopterygii) with a crushing feeding mechanism from the
      Middle Triassic of Guizhou (China).
AB  - BACKGROUND: Equipped with an effective predatory feeding mechanism enhanced by
      large and sharp teeth, pointed snout and elongate body, saurichthyiform fishes
      are considered common fish-eaters in the early Mesozoic aquatic ecosystems.
      Additionally, because of the similar body plan across species, saurichthyiforms
      are also regarded evolutionally conservative, with few morphological and
      ecological changes during their long history. However, their phylogenetic
      affinity remains unclear as to whether they are chondrostean, neopterygian or
      stem-actinopteran, and likewise the intrarelationships of the group have rarely
      been explored. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a new
      saurichthyiform from the Middle Triassic of Guizhou, China, based on the well
      preserved specimens including a 3-D braincase. The new taxon, Yelangichthys
      macrocephalus gen. et sp. nov., is unique among saurichthyiforms in having a
      peculiar neurocranium with a broad orbital tectum, paired posterior myodomes, a
      deep, transverse fossa in the posterodorsal part of the orbit, and a feeding
      mechanism structured for durophagy. Phylogenetic analysis places Yelangichthys
      gen. nov. at the most basal position in the Saurichthyiformes as the sister to
      Saurichthyidae, and a new family Yelangichthyidae is erected to include only Y.
      macrocephalus gen. et sp. nov. The monophyly of the Chondrostei comprising
      [Saurichthyiformes + Acipenseriformes] Birgeriiformes is supported, but not the
      monophyly of Saurichthys, the type genus of Saurichthyidae. With its outstanding
      osteological details, Yelangichthys gen. nov. greatly increases the neurocranial
      variations in saurichthyiforms, and its novel feeding structure suggests the
      consumption of hard-preys instead of fishes. CONCLUSIONS/SIGNIFICANCE: Our
      findings highlight the detailed osteology of a saurichthyiform braincase and its
      feeding design. We suggest that saurichthyiforms are closely allied to the
      Acipenseriformes. Saurichthyiforms were very diverse in the cranial osteology and
      they might have undergone a rapid evolutionary radiation via, for the new
      material here, transforming the feeding mechanism and thus exploiting the food
      resources unsuitable for other saurichthyiforms.

PMID- 24324658
TI  - Estimating the biases associated with self-perceived, self-reported, and measured
      BMI on mental health.
AB  - PURPOSE: The purpose of the study is to explore the relationship between
      individuals' perceptions of their weight-status, self-reported height and weight,
      and measured weight status. METHODS: A national survey of 9,248 adolescents (47%
      male) between the ages of 11 and 27 is analyzed to determine whether inaccuracies
      in reporting are caused by misperception or conscious intent, and whether there
      tends to be a systematic bias in how individuals self-report. Self-esteem was
      used as an example of an important outcome variable in order to illustrate the
      magnitudes of the biases that may arise when using different measures of body
      size. RESULTS: Our results indicate that measured obesity status is associated
      with the reduction in Rosenberg Self-Esteem (RSE) of 0.30 points (p-value 0.005)
      among adolescents and 0.20 points (p-value 0.002) among young adults; in
      addition, using self-reported height and weight as opposed to measured height and
      weight does not result in a statistically detectable difference in the estimates.
      CONCLUSIONS: Individuals' self-reports of height and weight are not as unreliable
      as we might have expected. Although estimates from measured height and weight are
      preferred, in the absence of such measures, self-reported measures would likely
      be a reliable alternative. The differences in self-perception of weight status,
      however, imply that it is not comparable to measured weight categories.

PMID- 24324659
TI  - Yield and economic performance of organic and conventional cotton-based farming
      systems--results from a field trial in India.
AB  - The debate on the relative benefits of conventional and organic farming systems
      has in recent time gained significant interest. So far, global agricultural
      development has focused on increased productivity rather than on a holistic
      natural resource management for food security. Thus, developing more sustainable
      farming practices on a large scale is of utmost importance. However, information
      concerning the performance of farming systems under organic and conventional
      management in tropical and subtropical regions is scarce. This study presents
      agronomic and economic data from the conversion phase (2007-2010) of a farming
      systems comparison trial on a Vertisol soil in Madhya Pradesh, central India. A
      cotton-soybean-wheat crop rotation under biodynamic, organic and conventional
      (with and without Bt cotton) management was investigated. We observed a
      significant yield gap between organic and conventional farming systems in the
      1(st) crop cycle (cycle 1: 2007-2008) for cotton (-29%) and wheat (-27%), whereas
      in the 2(nd) crop cycle (cycle 2: 2009-2010) cotton and wheat yields were similar
      in all farming systems due to lower yields in the conventional systems. In
      contrast, organic soybean (a nitrogen fixing leguminous plant) yields were
      marginally lower than conventional yields (-1% in cycle 1, -11% in cycle 2).
      Averaged across all crops, conventional farming systems achieved significantly
      higher gross margins in cycle 1 (+29%), whereas in cycle 2 gross margins in
      organic farming systems were significantly higher (+25%) due to lower variable
      production costs but similar yields. Soybean gross margin was significantly
      higher in the organic system (+11%) across the four harvest years compared to the
      conventional systems. Our results suggest that organic soybean production is a
      viable option for smallholder farmers under the prevailing semi-arid conditions
      in India. Future research needs to elucidate the long-term productivity and
      profitability, particularly of cotton and wheat, and the ecological impact of the
      different farming systems. 

PMID- 24324660
TI  - Immunophenotyping in myelodysplastic syndromes can add prognostic information to
      well-established and new clinical scores.
AB  - BACKGROUND: myelodysplastic syndromes (MDS) are a heterogeneous group of
      hematopoietic clonal disorders. So, prognostic variables are important to
      separate patients with a similar biology and clinical outcome. We compared the
      importance of risk stratification in primary MDS of IPSS and WPSS with the just
      described revision of IPSS (IPSS-R), and examined if variables obtained by bone
      marrow immunophenotyping could add prognostic information to any of the scores.
      METHODS: In this prospective study of 101 cases of primary MDS we compared the
      relation of patients' overall survival with WHO types, IPSS, IPSS-R, WPSS and
      phenotypic abnormalities of hematopoietic precursors. We examined aberrancies in
      myelomonocytic precursors and CD34(+) cells. Patients were censored when
      receiving chemotherapy or BM transplantation. Survival analysis was made by Cox
      regressions and stability of the models was examined by bootstrap resampling.
      RESULTS: MEDIAN AGE: 64 years (15-93). WHO types: 2 cases of 5q- syndrome, 7 of
      RA, 64 of RCDM and 28 of RAEB. In the univariate Cox analysis, increasing risk
      category of all scores, degree of anemia, higher percentage of BM blasts, higher
      number of CD34(+) cells and their myeloid fractions besides increasing number of
      phenotypic abnormalities detected were significantly associated with a shorter
      survival. In the multivariate analysis comparing the three scores, IPSS-R was the
      only independent risk factor. Comparing WPSS with phenotypic variables
      (CD34(+)/CD13(+) cells, CD34(+)/CD13(-) cells and "total alterations") the score
      and "CD34(+)/CD13(+) cells" remained in the model. When IPSS was tested together
      with these phenotypic variables, only "CD34(+)/CD13(+) cells", and "total
      alterations" remained in the model. Testing IPSS-R with the phenotypic variables
      studied, only the score and "CD34(+)/CD13(+) cells" entered the model.
      CONCLUSIONS: Immunophenotypic analysis of myelomonocytic progenitors provides
      additional prognostic information to all clinical scores studied. IPSS-R improved
      risk stratification in MDS compared to the former scores.

PMID- 24324661
TI  - Mechanisms of a human skeletal myotonia produced by mutation in the C-terminus of
      NaV1.4: is Ca2+ regulation defective?
AB  - Mutations in the cytoplasmic tail (CT) of voltage gated sodium channels cause a
      spectrum of inherited diseases of cellular excitability, yet to date only one
      mutation in the CT of the human skeletal muscle voltage gated sodium channel
      (hNaV1.4F1705I) has been linked to cold aggravated myotonia. The functional
      effects of altered regulation of hNaV1.4F1705I are incompletely understood. The
      location of the hNaV1.4F1705I in the CT prompted us to examine the role of Ca(2+)
      and calmodulin (CaM) regulation in the manifestations of myotonia. To study Na
      channel related mechanisms of myotonia we exploited the differences in rat and
      human NaV1.4 channel regulation by Ca(2+) and CaM. hNaV1.4F1705I inactivation
      gating is Ca(2+)-sensitive compared to wild type hNaV1.4 which is Ca(2+)
      insensitive and the mutant channel exhibits a depolarizing shift of the V1/2 of
      inactivation with CaM over expression. In contrast the same mutation in the
      rNaV1.4 channel background (rNaV1.4F1698I) eliminates Ca(2+) sensitivity of
      gating without affecting the CaM over expression induced hyperpolarizing shift in
      steady-state inactivation. The differences in the Ca(2+) sensitivity of gating
      between wild type and mutant human and rat NaV1.4 channels are in part mediated
      by a divergence in the amino acid sequence in the EF hand like (EFL) region of
      the CT. Thus the composition of the EFL region contributes to the species
      differences in Ca(2+)/CaM regulation of the mutant channels that produce
      myotonia. The myotonia mutation F1705I slows INa decay in a Ca(2+)-sensitive
      fashion. The combination of the altered voltage dependence and kinetics of INa
      decay contribute to the myotonic phenotype and may involve the Ca(2+)-sensing
      apparatus in the CT of NaV1.4. 

PMID- 24324662
TI  - Association between birth order and emergency room visits and acute hospital
      admissions following pediatric vaccination: a self-controlled study.
AB  - OBJECTIVE: We investigated the association between a child's birth order and
      emergency room (ER) visits and hospital admissions following 2-,4-,6- and 12
      month pediatric vaccinations. METHODS: We included all children born in Ontario
      between April 1(st), 2006 and March 31(st), 2009 who received a qualifying
      vaccination. We identified vaccinations, ER visits and admissions using health
      administrative data housed at the Institute for Clinical Evaluative Sciences. We
      used the self-controlled case series design to compare the relative incidence
      (RI) of events among 1(st)-born and later-born children using relative incidence
      ratios (RIR). RESULTS: For the 2-month vaccination, the RIR for 1(st)-borns
      versus later-born children was 1.37 (95% CI: 1.19-1.57), which translates to 112
      additional events/100,000 vaccinated. For the 4-month vaccination, the RIR for
      1(st)-borns vs. later-borns was 1.70 (95% CI: 1.45-1.99), representing 157
      additional events/100,000 vaccinated. At 6 months, the RIR for 1(st) vs. later
      borns was 1.27 (95% CI: 1.09-1.48), or 77 excess events/100,000 vaccinated. At
      the 12-month vaccination, the RIR was 1.11 (95% CI: 1.02-1.21), or 249 excess
      events/100,000 vaccinated. CONCLUSIONS: Birth order is associated with increased
      incidence of ER visits and hospitalizations following vaccination in infancy.
      1(st)-born children had significantly higher relative incidence of events
      compared to later-born children.

PMID- 24324663
TI  - Gas chromatography-mass spectrometry based metabolomic approach for optimization
      and toxicity evaluation of earthworm sub-lethal responses to carbofuran.
AB  - Despite recent advances in understanding mechanism of toxicity, the development
      of biomarkers (biochemicals that vary significantly with exposure to chemicals)
      for pesticides and environmental contaminants exposure is still a challenging
      task. Carbofuran is one of the most commonly used pesticides in agriculture and
      said to be most toxic carbamate pesticide. It is necessary to identify the
      biochemicals that can vary significantly after carbofuran exposure on earthworms
      which will help to assess the soil ecotoxicity. Initially, we have optimized the
      extraction conditions which are suitable for high-throughput gas chromatography
      mass spectrometry (GC-MS) based metabolomics for the tissue of earthworm,
      Metaphire posthuma. Upon evaluation of five different extraction solvent systems,
      80% methanol was found to have good extraction efficiency based on the yields of
      metabolites, multivariate analysis, total number of peaks and reproducibility of
      metabolites. Later the toxicity evaluation was performed to characterize the
      tissue specific metabolomic perturbation of earthworm, Metaphire posthuma after
      exposure to carbofuran at three different concentration levels (0.15, 0.3 and 0.6
      mg/kg of soil). Seventeen metabolites, contributing to the best classification
      performance of highest dose dependent carbofuran exposed earthworms from healthy
      controls were identified. This study suggests that GC-MS based metabolomic
      approach was precise and sensitive to measure the earthworm responses to
      carbofuran exposure in soil, and can be used as a promising tool for
      environmental eco-toxicological studies. 

PMID- 24324664
TI  - Sex-differences and temporal consistency in stickleback fish boldness.
AB  - Behavioural traits that co-vary across contexts or situations often reflect
      fundamental trade-offs which individuals experience in different contexts (e.g.
      fitness trade-offs between exploration and predation risk). Since males tend to
      experience greater variance in reproductive success than females, there may be
      considerable fitness benefits associated with "bolder" behavioural types, but
      only recently have researchers begun to consider sex-specific and life-history
      strategies associated with these. Here we test the hypothesis that male three
      spined sticklebacks (Gasterosteus aculeatus) show high risk but potentially high
      return behaviours compared to females. According to this hypothesis we predicted
      that male fish would show greater exploration of their environment in a foraging
      context, and be caught sooner by an experimenter than females. We found that the
      time fish spent out of cover exploring their environment was correlated over two
      days, and males spent significantly more time out of cover than females. Also,
      the order in which fish were net-caught from their holding aquarium by an
      experimenter prior to experiments was negatively correlated with the time spent
      out of cover during tests, and males tended to be caught sooner than females.
      Moreover, we found a positive correlation between the catch number prior to our
      experiments and nine months after, pointing towards consistent, long-term
      individual differences in behaviour. 

PMID- 24324665
TI  - Limitations to reproductive success in the dioecious tree Rhamnus davurica.
AB  - The reproductive success of a female plant in a dioecious species may be affected
      by pollen limitation and resource limitation. This study presents evidence that
      the reproductive success of the dioecious understorey tree species, Rhamnus
      davurica, is affected by the distance to the nearest male. The sex ratios were
      female-biased, although showing fluctuations in the three years of conducting the
      study. The mortality rate of females was higher than that of males indicating a
      trade-off between reproduction and survival. Altogether 49 females, designated as
      "focal females", were randomly selected for monitoring their reproductive status
      between April and October in 2010. But successful reproduction (meaning that the
      flowering female trees had fruit in the fruiting season) was observed only in 28
      females in 2011 and 16 females in 2012. The method of path analysis was applied
      to determine the effect of topography, local competition and proximity to the
      nearest male on the fruit set of the females. In the three years of the study,
      elevation, competition and female size had no significant effect on the fruit
      set. The distance to the nearest male, however, had a significant effect on fruit
      set. Number of fruits and fruit set were decreased with increasing distance to
      the nearest male. It was possible to estimate maximum fruit set, based on the
      comparatively large dataset. The number of fruits and the fruit set are
      exponentially related to the distance to the nearest male and the relationships
      are described by an exponential model. The results of this study support the
      importance of pollen limitation on the reproductive success in Rhamnus davurica. 

PMID- 24324666
TI  - Vitamin D status among pulmonary TB patients and non-TB controls: a cross
      sectional study from Mwanza, Tanzania.
AB  - BACKGROUND: Little is known about vitamin D status in low-income populations
      burdened with infectious diseases. Hence, there is a need for data on correlates
      of serum 25-hydroxy vitamin D (S-25(OH)D) and its validity during infections.
      OBJECTIVE: To assess the role of pulmonary TB (PTB) and HIV as correlates of S
      25(OH)D. DESIGN: Age-sex-matched cross-sectional study among PTB patients and non
      TB controls. METHODS: PTB patients were categorized as sputum negative (PTB-) and
      positive (PTB+) by culture. Non-TB controls were randomly selected among age-sex
      matched neighbours to PTB+ patients. Height, weight, arm circumference and
      triceps skinfold were measured, and body mass index (BMI), arm fat (AFA) and
      muscle area (AMA) computed. HIV status, and S-25(OH)D, C-reactive protein (S-CRP)
      and alpha1-acid glycoprotein (S-AGP) were determined. Linear regression analysis
      with controls and PTB patients combined was used to identify correlates of S
      25(OH)D. RESULTS: S-25(OH)D data were available on 97.8% (1570) of 1605
      participants. Mean (SD) S-25(OH)D was 84.4 (25.6) nmol/L with 39.6% <75 nmol/L
      among 347 non-TB controls. Time of recruitment, sex, PTB and HIV, and elevated S
      AGP were correlates of S-25(OH)D. S-25(OH)D was 24.8 (95% CI 18.6;30.9) nmol/L
      higher in PTB compared to controls among females, but only 9.8 (95% CI:4.5;15.2)
      nmol/L among males (interaction p<0.0001). Females had 13.8 (95% CI:8.2;21.9)
      nmol/L lower S-25(OH)D than males, and HIV infected individuals had 8.5 (95%
      CI:4.9;12.1) higher S-25(OH)D compared to uninfected. Elevated S-AGP was a
      positive correlate of S-25(OH)D. Low BMI was associated with S-25(OH)D, but not
      with infections or S-AGP in the model. CONCLUSION: While S-25(OH)D may decline
      transiently during a mild acute phase response, it may increase if the acute
      phase response leads to loss of fat. The validity of S-25(OH)D as a marker of
      vitamin D status may be affected by infections.

PMID- 24324667
TI  - A reference methylome database and analysis pipeline to facilitate integrative
      and comparative epigenomics.
AB  - DNA methylation is implicated in a surprising diversity of regulatory,
      evolutionary processes and diseases in eukaryotes. The introduction of whole
      genome bisulfite sequencing has enabled the study of DNA methylation at a single
      base resolution, revealing many new aspects of DNA methylation and highlighting
      the usefulness of methylome data in understanding a variety of genomic phenomena.
      As the number of publicly available whole-genome bisulfite sequencing studies
      reaches into the hundreds, reliable and convenient tools for comparing and
      analyzing methylomes become increasingly important. We present MethPipe, a
      pipeline for both low and high-level methylome analysis, and MethBase, an
      accompanying database of annotated methylomes from the public domain. Together
      these resources enable researchers to extract interesting features from
      methylomes and compare them with those identified in public methylomes in our
      database. 

PMID- 24324668
TI  - A quantitative assessment of the role of the parasite Amoebophrya in the
      termination of Alexandrium fundyense blooms within a small coastal embayment.
AB  - Parasitic dinoflagellates of the genus Amoebophrya infect free-living
      dinoflagellates, some of which can cause harmful algal blooms (HABs). High
      prevalence of Amoebophrya spp. has been linked to the decline of some HABs in
      marine systems. The objective of this study was to evaluate the impact of
      Amoebophrya spp. on the dynamics of dinoflagellate blooms in Salt Pond (MA, USA),
      particularly the harmful species Alexandrium fundyense. The abundance of
      Amoebophrya life stages was estimated 3-7 days per week through the full duration
      of an annual A. fundyense bloom using fluorescence in situ hybridization coupled
      with tyramide signal amplification (FISH-TSA). More than 20 potential hosts were
      recorded including Dinophysis spp., Protoperidinium spp. and Gonyaulax spp., but
      the only dinoflagellate cells infected by Amoebophrya spp. during the sampling
      period were A. fundyense. Maximum A. fundyense concentration co-occurred with an
      increase of infected hosts, followed by a massive release of Amoebophrya
      dinospores in the water column. On average, Amoebophrya spp. infected and killed
      ~30% of the A. fundyense population per day in the end phase of the bloom. The
      decline of the host A. fundyense population coincided with a dramatic life-cycle
      transition from vegetative division to sexual fusion. This transition occurred
      after maximum infected host concentrations and before peak infection percentages
      were observed, suggesting that most A. fundyense escaped parasite infection
      through sexual fusion. The results of this work highlight the importance of high
      frequency sampling of both parasite and host populations to accurately assess the
      impact of parasites on natural plankton assemblages.

PMID- 24324669
TI  - The tip of the "celiac iceberg" in China: a systematic review and meta-analysis.
AB  - OBJECTIVE: Until recently, celiac disease was considered to be rare in China. We
      aimed to estimate its true status. METHODS: By searching the MEDLINE database and
      four Chinese full-text databases (CNKI, CBM, VIP and WANFANG) (up to August
      2012), as well as two HLA allele frequency net databases and the Chinese
      Statistics Yearbook databases, we systematically reviewed the literature on
      definite and suspected cases of celiac disease, the predisposing HLA allele
      frequencies, and on gluten exposure in China. Meta-analysis was performed by
      analyzing DQ2, DQ8 and DQB1*0201 gene frequencies and heterogeneity in
      populations from different geographic regions and ethnicities in China. RESULTS:
      At present, the number of reported celiac disease cases is extremely low in
      China. The frequencies of the HLA-DQ2.5 and HLA-DQ8 haplotypes were 3.4% (95%
      confidence interval 1.3-5.5%) and 2.1% (0.1-4.1%), respectively. HLA-DQ2 and HLA
      DQ8 antigen frequencies were 18.4% (15.0-21.7%) and 8.0% (4.5-11.4%),
      respectively. The frequency of the DQB1*0201 allele was 10.5% (9.3-11.6%) and it
      was more common in the northern Chinese than in the southern Chinese populations.
      The chance of being exposed to gluten is rapidly increasing all over China
      nowadays. CONCLUSION: The data on HLA haplotyping, in conjunction with increasing
      wheat consumption, strongly suggests that the occurrence of celiac disease is
      more common in China than currently reported. Coordinated measures by the Chinese
      government, medical and agricultural research institutions, and food industries,
      would be justified to create more awareness about celiac disease and to prevent
      it becoming a medical and societal burden.

PMID- 24324670
TI  - Biotyping and genotyping (MLVA16) of Brucella abortus isolated from cattle in
      Brazil, 1977 to 2008.
AB  - Brucellosis is a worldwide distributed zoonosis that causes important economic
      losses to animal production. In Brazil, information on the distribution of
      biovars and genotypes of Brucella spp. is scarce or unavailable. This study aimed
      (i) to biotype and genotype 137 Brazilian cattle isolates (from 1977 to 2008) of
      B. abortus and (ii) to analyze their distribution. B. abortus biovars 1, 2 and 3
      (subgroup 3b) were confirmed and biovars 4 and 6 were first described in Brazil.
      Genotyping by the panel 1 revealed two groups, one clustering around genotype 40
      and another around genotype 28. Panels 2A and 2B disclosed a high diversity among
      Brazilian B. abortus strains. Eighty-nine genotypes were found by MLVA16. MLVA16
      panel 1 and 2 showed geographic clustering of some genotypes. Biotyping and
      MLVA16 genotyping of Brazilian B. abortus isolates were useful to better
      understand the epidemiology of bovine brucellosis in the region. 

PMID- 24324672
TI  - Enhanced production of green tide algal biomass through additional carbon supply.
AB  - Intensive algal cultivation usually requires a high flux of dissolved inorganic
      carbon (Ci) to support productivity, particularly for high density algal
      cultures. Carbon dioxide (CO2) enrichment can be used to overcome Ci limitation
      and enhance productivity of algae in intensive culture, however, it is unclear
      whether algal species with the ability to utilise bicarbonate (HCO3 (-)) as a
      carbon source for photosynthesis will benefit from CO2 enrichment. This study
      quantified the HCO3 (-) affinity of three green tide algal species, Cladophora
      coelothrix, Cladophora patentiramea and Chaetomorpha linum, targeted for biomass
      and bioenergy production. Subsequently, we quantified productivity and carbon,
      nitrogen and ash content in response to CO2 enrichment. All three species had
      similar high pH compensation points (9.7-9.9), and grew at similar rates up to pH
      9, demonstrating HCO3 (-) utilization. Algal cultures enriched with CO2 as a
      carbon source had 30% more total Ci available, supplying twenty five times more
      CO2 than the control. This higher Ci significantly enhanced the productivity of
      Cladophora coelothrix (26%), Chaetomorpha linum (24%) and to a lesser extent for
      Cladophora patentiramea (11%), compared to controls. We demonstrated that
      supplying carbon as CO2 can enhance the productivity of targeted green tide algal
      species under intensive culture, despite their clear ability to utilise HCO3 (-).

PMID- 24324671
TI  - Canonical Wnt/beta-catenin signalling is essential for optic cup formation.
AB  - A multitude of signalling pathways are involved in the process of forming an eye.
      Here we demonstrate that beta-catenin is essential for eye development as
      inactivation of beta-catenin prior to cellular specification in the optic vesicle
      caused anophthalmia in mice. By achieving this early and tissue-specific beta
      catenin inactivation we find that retinal pigment epithelium (RPE) commitment was
      blocked and eye development was arrested prior to optic cup formation due to a
      loss of canonical Wnt signalling in the dorsal optic vesicle. Thus, these results
      show that Wnt/beta-catenin signalling is required earlier and play a more central
      role in eye development than previous studies have indicated. In our genetic
      model system a few RPE cells could escape beta-catenin inactivation leading to
      the formation of a small optic rudiment. The optic rudiment contained several
      neural retinal cell classes surrounded by an RPE. Unlike the RPE cells, the
      neural retinal cells could be beta-catenin-negative revealing that
      differentiation of the neural retinal cell classes is beta-catenin-independent.
      Moreover, although dorsoventral patterning is initiated in the mutant optic
      vesicle, the neural retinal cells in the optic rudiment displayed almost
      exclusively ventral identity. Thus, beta-catenin is required for optic cup
      formation, commitment to RPE cells and maintenance of dorsal identity of the
      retina. 

PMID- 24324674
TI  - A new distribution-free approach to constructing the confidence region for
      multiple parameters.
AB  - Construction of confidence intervals or regions is an important part of
      statistical inference. The usual approach to constructing a confidence interval
      for a single parameter or confidence region for two or more parameters requires
      that the distribution of estimated parameters is known or can be assumed. In
      reality, the sampling distributions of parameters of biological importance are
      often unknown or difficult to be characterized. Distribution-free nonparametric
      resampling methods such as bootstrapping and permutation have been widely used to
      construct the confidence interval for a single parameter. There are also several
      parametric (ellipse) and nonparametric (convex hull peeling, bagplot and
      HPDregionplot) methods available for constructing confidence regions for two or
      more parameters. However, these methods have some key deficiencies including
      biased estimation of the true coverage rate, failure to account for the shape of
      the distribution inherent in the data and difficulty to implement. The purpose of
      this paper is to develop a new distribution-free method for constructing the
      confidence region that is based only on a few basic geometrical principles and
      accounts for the actual shape of the distribution inherent in the real data. The
      new method is implemented in an R package, distfree.cr/R. The statistical
      properties of the new method are evaluated and compared with those of the other
      methods through Monte Carlo simulation. Our new method outperforms the other
      methods regardless of whether the samples are taken from normal or non-normal
      bivariate distributions. In addition, the superiority of our method is consistent
      across different sample sizes and different levels of correlation between the two
      variables. We also analyze three biological data sets to illustrate the use of
      our new method for genomics and other biological researches. 

PMID- 24324673
TI  - Prokineticin receptor 1 as a novel suppressor of preadipocyte proliferation and
      differentiation to control obesity.
AB  - BACKGROUND: Adipocyte renewal from preadipocytes occurs throughout the lifetime
      and contributes to obesity. To date, little is known about the mechanisms that
      control preadipocyte proliferation and differentiation. Prokineticin-2 is an
      angiogenic and anorexigenic hormone that activate two G protein-coupled receptors
      (GPCRs): PKR1 and PKR2. Prokineticin-2 regulates food intake and energy
      metabolism via central mechanisms (PKR2). The peripheral effect of prokineticin-2
      on adipocytes/preadipocytes has not been studied yet. METHODOLOGY/PRINCIPAL
      FINDINGS: Since adipocytes and preadipocytes express mainly prokineticin receptor
      1 (PKR1), here, we explored the role of PKR1 in adipose tissue expansion,
      generating PKR1-null (PKR1(-/-)) and adipocyte-specific (PKR1(ad-/-)) mutant
      mice, and using murine and human preadipocyte cell lines. Both PKR1(-/-) and
      PKR1(ad-/-) had excessive abdominal adipose tissue, but only PKR1(-/-) mice
      showed severe obesity and diabetes-like syndrome. PKR1(ad-/-)) mice had increased
      proliferating preadipocytes and newly formed adipocyte levels, leading to
      expansion of adipose tissue. Using PKR1-knockdown in 3T3-L1 preadipocytes, we
      show that PKR1 directly inhibits preadipocyte proliferation and differentiation.
      These PKR1 cell autonomous actions appear targeted at preadipocyte cell cycle
      regulatory pathways, through reducing cyclin D, E, cdk2, c-Myc levels.
      CONCLUSIONS/SIGNIFICANCE: These results suggest PKR1 to be a crucial player in
      the preadipocyte proliferation and differentiation. Our data should facilitate
      studies of both the pathogenesis and therapy of obesity in humans.

PMID- 24324675
TI  - Efficient video panoramic image stitching based on an improved selection of
      Harris corners and a multiple-constraint corner matching.
AB  - Video panoramic image stitching is extremely time-consuming among other
      challenges. We present a new algorithm: (i) Improved, self-adaptive selection of
      Harris corners. The successful stitching relies heavily on the accuracy of corner
      selection. We fragment each image into numerous regions and select corners within
      each region according to the normalized variance of region grayscales. Such a
      selection is self-adaptive and guarantees that corners are distributed
      proportional to region texture information. The possible clustering of corners is
      also avoided. (ii) Multiple-constraint corner matching. The traditional Random
      Sample Consensus (RANSAC) algorithm is inefficient, especially when handling a
      large number of images with similar features. We filter out many inappropriate
      corners according to their position information, and then generate candidate
      matching pairs based on grayscales of adjacent regions around corners. Finally we
      apply multiple constraints on every two pairs to remove incorrectly matched
      pairs. By a significantly reduced number of iterations needed in RANSAC, the
      stitching can be performed in a much more efficient manner. Experiments
      demonstrate that (i) our corner matching is four times faster than normalized
      cross-correlation function (NCC) rough match in RANSAC and (ii) generated
      panoramas feature a smooth transition in overlapping image areas and satisfy real
      time human visual requirements. 

PMID- 24324676
TI  - Development and evaluation of a novel (99m)tc-labeled annexin A5 for early
      detection of response to chemotherapy.
AB  - (99m)Tc-HYNIC-annexin A5 can be considered as a benchmark in the field of
      apoptosis imaging. However, (99m)Tc-HYNIC-annexin A5 has characteristics of high
      uptake and long retention in non-target tissues such as kidney and liver. To
      minimize this problem, we developed a novel (99m)Tc-labeled annexin A5 using a
      bis(hydroxamamide) derivative [C3(BHam)2] as a bifunctional chelating agent, and
      evaluated its usefulness as an imaging agent for detecting apoptosis. The amino
      group of C3(BHam)2 was converted to a maleimide group, and was coupled to thiol
      groups of annexin A5 pretreated with 2-iminothiolane. (99m)Tc labeling was
      performed by a ligand exchange reaction with (99m)Tc-glucoheptonate.
      Biodistribution experiments for both (99m)Tc-C3(BHam)2-annexin A5 and (99m)Tc
      HYNIC-annexin A5 were performed in normal mice. In addition, in tumor-bearing
      mice, the relationship between the therapeutic effects of chemotherapy (5-FU) and
      the tumor accumulation of (99m)Tc-C3(BHam)2-annexin A5 just after the first
      treatment of 5-FU was evaluated. (99m)Tc-C3(BHam)2-annexin A5 was prepared with a
      radiochemical purity of over 95%. In biodistribution experiments, (99m)Tc
      C3(BHam)2-annexin A5 had a much lower kidney accumulation of radioactivity than
      (99m)Tc-HYNIC-annexin A5. In the organs for metabolism, such as liver and kidney,
      radioactivity after the injection of (99m)Tc-HYNIC-annexin A5 was residual for a
      long time. On the other hand, radioactivity after the injection of (99m)Tc
      C3(BHam)2-annexin A5 gradually decreased. In therapeutic experiments, tumor
      growth in the mice treated with 5-FU was significantly inhibited. Accumulation of
      (99m)Tc-C3(BHam)2-annexin A5 in tumors significantly increased after 5-FU
      treatment. The accumulation of radioactivity in tumor correlated positively with
      the counts of TUNEL-positive cells. These findings suggest that (99m)Tc-C3(BHam)2
      annexin A5 may contribute to the efficient detection of apoptotic tumor response
      after chemotherapy. 

PMID- 24324677
TI  - Learning to make collective decisions: the impact of confidence escalation.
AB  - Little is known about how people learn to take into account others' opinions in
      joint decisions. To address this question, we combined computational and
      empirical approaches. Human dyads made individual and joint visual perceptual
      decision and rated their confidence in those decisions (data previously
      published). We trained a reinforcement (temporal difference) learning agent to
      get the participants' confidence level and learn to arrive at a dyadic decision
      by finding the policy that either maximized the accuracy of the model decisions
      or maximally conformed to the empirical dyadic decisions. When confidences were
      shared visually without verbal interaction, RL agents successfully captured
      social learning. When participants exchanged confidences visually and interacted
      verbally, no collective benefit was achieved and the model failed to predict the
      dyadic behaviour. Behaviourally, dyad members' confidence increased progressively
      and verbal interaction accelerated this escalation. The success of the model in
      drawing collective benefit from dyad members was inversely related to confidence
      escalation rate. The findings show an automated learning agent can, in principle,
      combine individual opinions and achieve collective benefit but the same agent
      cannot discount the escalation suggesting that one cognitive component of
      collective decision making in human may involve discounting of overconfidence
      arising from interactions. 

PMID- 24324678
TI  - Lack of relationship between cord serum angiopoietin-like protein 4 (ANGPTL4) and
      lipolytic activity in human neonates born by spontaneous delivery.
AB  - BACKGROUND: Ligands of peroxisome-proliferator activated receptors (PPARs), such
      as non-esterified fatty acids (NEFAs), induce expression of angiopoietin-like
      protein 4 (ANGPTL4). Recently ANGPTL4 has been reported to be a mediator of
      intracellular adipose lipolysis induced by glucocorticoids. OBJECTIVE: To
      determine the concentrations of ANGPTL4 in cord serum of neonates born by
      spontaneous vaginal delivery (SVD) and by pre-labor cesarean section (CS) from
      healthy women, and to relate them to parameters of neonatal lipolytic activity at
      birth. MEASUREMENTS: In 54 neonates born by SVD and in 56 neonates born by CS,
      arterial cord blood was drawn to determine insulin, cortisol, triacylglycerols
      (TAGs), glycerol, non-esterified fatty acids (NEFAs), individual fatty acids,
      ANGPTL4, adiponectin, retinol binding protein 4 (RBP4) and leptin. RESULTS: Birth
      weight and neonatal fat mass in SVD and CS showed no difference, but the
      concentrations of glycerol, adiponectin, RBP4, NEFAs and most individual fatty
      acids were higher in cord serum of neonates born by SVD compared to CS,
      indicating a higher adipose tissue breakdown in the SVD group. The concentrations
      of TAG and cortisol were also higher and that of insulin was lower in cord serum
      of SVD compared to the CS group. However, the concentration in cord serum of
      ANGPTL4 did not differ between the two groups and no positive correlation with
      either NEFA or glycerol concentrations were detected. CONCLUSION: ANGPTL4 is
      known to stimulate lipolysis in adults, but does not appear to mediate the
      increased activity in SVD, indicating the presence of different regulatory
      inputs.

PMID- 24324679
TI  - Perception of social cues of danger in autism spectrum disorders.
AB  - Intuitive grasping of the meaning of subtle social cues is particularly affected
      in autism spectrum disorders (ASD). Despite their relevance in social
      communication, the effect of averted gaze in fearful faces in conveying a signal
      of environmental threat has not been investigated using real face stimuli in
      adults with ASD. Here, using functional MRI, we show that briefly presented
      fearful faces with averted gaze, previously shown to be a strong communicative
      signal of environmental danger, produce different patterns of brain activation
      than fearful faces with direct gaze in a group of 26 normally intelligent adults
      with ASD compared with 26 matched controls. While implicit cue of threat produces
      brain activation in attention, emotion processing and mental state attribution
      networks in controls, this effect is absent in individuals with ASD. Instead,
      individuals with ASD show activation in the subcortical face-processing system in
      response to direct eye contact. An effect of differences in looking behavior was
      excluded in a separate eye tracking experiment. Our data suggest that individuals
      with ASD are more sensitive to direct eye contact than to social signals of
      danger conveyed by averted fearful gaze. 

PMID- 24324680
TI  - Trends in antibiotic treatment of acute otitis media and treatment failure in
      children, 2000-2011.
AB  - OBJECTIVES: Guidelines to treat acute otitis media (AOM) were published in 2004.
      Initial declines in prescribing were shown, but it's unknown if they were
      sustained. We examine trends in antibiotic dispensing patterns to treat AOM among
      a large population of children. We also document trends in antibiotic failure.
      STUDY DESIGN: Children aged 3 months to 12 years with an AOM diagnosis, enrolled
      in a commercial claims database between January 1, 2000-December 31, 2011 were
      included. Pharmacy claims within 7 days of diagnosis were searched for antibiotic
      prescriptions. Antibiotic failure was defined as a dispensing of a different
      antibiotic class within 2-18 days after the first prescription. We analyzed
      trends in antibiotic use and failure by class of antibiotic and year. RESULTS: We
      identified over 4 million children under 13 years with AOM. The proportion of
      antibiotic dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which
      the instances of dispensing rebounded to pre-guideline levels. However, levels
      began decreasing again in 2010 and the antibiotic use rate in 2011 was 57.6%.
      Cephalosporin prescriptions increased by 41.5% over eleven years. Antibiotic
      failure decreased slightly, and macrolides had the lowest proportion of failures,
      while all other classes had failure rates around 10%. CONCLUSIONS: In recent
      years, antibiotic dispensing to treat AOM remains high. In addition, the use of
      broad-spectrum antibiotics is increasing despite having a high rate of treatment
      failure. Overprescribing of antibiotics and use of non-penicillin therapy for AOM
      treatment could lead to the development of antibiotic-resistant infections.

PMID- 24324681
TI  - Evaluation of the protective immunity of a novel subunit fusion vaccine in a
      murine model of systemic MRSA infection.
AB  - Staphylococcus aureus is a common commensal organism in humans and a major cause
      of bacteremia and hospital acquired infection. Because of the spread of strains
      resistant to antibiotics, these infections are becoming more difficult to treat.
      Therefore, exploration of anti-staphylococcal vaccines is currently a high
      priority. Iron surface determinant B (IsdB) is an iron-regulated cell wall
      anchored surface protein of S. aureus. Alpha-toxin (Hla) is a secreted cytolytic
      pore-forming toxin. Previous studies reported that immunization with IsdB or Hla
      protected animals against S. aureus infection. To develop a broadly protective
      vaccine, we constructed chimeric vaccines based on IsdB and Hla. Immunization
      with the chimeric bivalent vaccine induced strong antibody and T cell responses.
      When the protective efficacy of the chimeric bivalent vaccine was compared to
      that of individual proteins in a murine model of systemic S. aureus infection,
      the bivalent vaccine showed a stronger protective immune response than the
      individual proteins (IsdB or Hla). Based on the results presented here, the
      chimeric bivalent vaccine affords higher levels of protection against S. aureus
      and has potential as a more effective candidate vaccine. 

PMID- 24324682
TI  - Clinical impact of the temporal relationship between depression and type 2
      diabetes: the Fremantle diabetes study phase II.
AB  - BACKGROUND: The clinical features of type 2 diabetes may differ depending on
      whether first depression episode precedes or follows the diagnosis of diabetes.
      METHODS: Type 2 patients from the observational community-based Fremantle
      Diabetes Study Phase II underwent assessment of lifetime depression using the
      Brief Lifetime Depression Scale (developed and validated for this study)
      supplemented by information on current depression symptoms (Patient Health
      Questionnaire, 9-item version) and use of antidepressants. Patients were
      categorized as never depressed (Group 1), having had depression before diabetes
      diagnosis (Group 2), diagnosed with depression and diabetes within 2 years of
      each other (Group 3) and having depression after diabetes diagnosis (Group 4).
      RESULTS: Of 1391 patients, 20.8% were assigned to Group 2, 6.0% to Group 3 and
      14.5% to Group 4. In Group 2, depression occurred a median 15.6 years before
      diabetes onset at age 37.2+/-14.7 years. These patients had similar clinical
      characteristics to never depressed patients except for reduced self-care
      behaviours and having more symptomatic peripheral arterial disease. In Group 4,
      depression occurred a median 9.9 years after diabetes onset at age 59.8+/-13.0
      years. These patients had long duration diabetes, poor glycaemic control, more
      intensive management and more diabetic complications. Group 4 patients had more
      current depression than Group 2 but were less likely to be receiving
      antidepressants. CONCLUSIONS/INTERPRETATION: The clinical features of depression
      and type 2 diabetes are heterogeneous depending on their temporal relationship.
      There may be corresponding differences in the pathogenesis of depression in
      diabetes that have implications for diagnosis and management.

PMID- 24324683
TI  - Lack of RNase L attenuates macrophage functions.
AB  - BACKGROUND: Macrophages are one of the major cell types in innate immunity
      against microbial infection. It is believed that the expression of
      proinflammatory genes such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, IL-6, and cyclooxygenase-2 (Cox-2) by macrophages is also
      crucial for activation of both innate and adaptive immunities. RNase L is an
      interferon (IFN) inducible enzyme which is highly expressed in macrophages. It
      has been demonstrated that RNase L regulates the expression of certain
      inflammatory genes. However, its role in macrophage function is largely unknown.
      METHODOLOGY: Bone marrow-derived macrophages (BMMs) were generated from RNase
      L(+/+)and (-/-) mice. The migration of BMMs was analyzed by using Transwell
      migration assays. Endocytosis and phagocytosis of macrophages were assessed by
      using fluorescein isothiocyanate (FITC)-Dextran 40,000 and FITC-E. coli bacteria,
      respectively. The expression of inflammatory genes was determined by Western Blot
      and ELISA. The promoter activity of Cox-2 was measured by luciferase reporter
      assays. CONCLUSIONS/FINDINGS: Lack of RNase L significantly decreased the
      migration of BMMs induced by M-CSF, but at a less extent by GM-CSF and chemokine
      C-C motif ligand-2 (CCL2). Interestingly, RNase L deficient BMMs showed a
      significant reduction of endocytic activity to FITC-Dextran 40,000, but no any
      obvious effect on their phagocytic activity to FITC-bacteria under the same
      condition. RNase L impacts the expression of certain genes related to cell
      migration and inflammation such as transforming growth factor (TGF)-beta, IL
      1beta, IL-10, CCL2 and Cox-2. Furthermore, the functional analysis of the Cox-2
      promoter revealed that RNase L regulated the expression of Cox-2 in macrophages
      at its transcriptional level. Taken together, our findings provide direct
      evidence showing that RNase L contributes to innate immunity through regulating
      macrophage functions.

PMID- 24324684
TI  - Helical antifreeze proteins have independently evolved in fishes on four
      occasions.
AB  - Alanine-rich alpha-helical (type I) antifreeze proteins (AFPs) are produced by a
      variety of fish species from three different orders to protect against freezing
      in icy seawater. Interspersed amongst and within these orders are fishes making
      AFPs that are completely different in both sequence and structure. The origin of
      this variety of types I, II, III and antifreeze glycoproteins (AFGPs) has been
      attributed to adaptation following sea-level glaciations that occurred after the
      divergence of most of the extant families of fish. The presence of similar types
      of AFPs in distantly related fishes has been ascribed to lateral gene transfer in
      the case of the structurally complex globular type II lectin-like AFPs and to
      convergent evolution for the AFGPs, which consist of a well-conserved tripeptide
      repeat. In this paper, we examine the genesis of the type I AFPs, which are
      intermediate in complexity. These predominantly alpha-helical peptides share many
      features, such as putative capping structures, Ala-richness and amphipathic
      character. We have added to the type I repertoire by cloning additional sequences
      from sculpin and have found that the similarities between the type I AFPs of the
      four distinct groups of fishes are not borne out at the nucleotide level. Both
      the non-coding sequences and the codon usage patterns are strikingly different.
      We propose that these AFPs arose via convergence from different progenitor
      helices with a weak affinity for ice and that their similarity is dictated by the
      propensity of specific amino acids to form helices and to align water on one side
      of the helix into an ice-like pattern. 

PMID- 24324685
TI  - The elimination of DNA from the Cry toxin-DNA complex is a necessary step in the
      mode of action of the Cry8 toxin.
AB  - Several crystal (Cry) proteins are known to occur as DNA-protein complexes.
      However, the role of the DNA associated with the activated toxin in the mechanism
      of action of the Cry toxin has long been ignored. Here, we focused on the DNA
      activated Cry toxin complex. Both forms of the Cry8Ca2 and Cry8Ea1 toxins, i.e.,
      with or without bound DNA, were separately obtained. Size-exclusion
      chromatography analysis indicated that the Cry8Ca2 toxin-DNA complex has a tight
      or compact structure. The Cry8Ca2 toxin-DNA complex is more likely to move toward
      the air/water interface and is more hydrophobic than the toxin without DNA.
      Competitive binding assays indicated that the Cry8Ca2 and Cry8Ea1 toxins without
      DNA specifically bind to the midgut of Anomala corpulenta and Holotrichia
      parallela larvae, respectively. In contrast, the association of DNA with each
      toxin might result in the nonspecific recognition of the Cry toxin and its target
      receptor in the insect midgut. The association of the DNA fragment with the Cry8
      toxin was shown to protect the Cry protein from digestion by proteases. Based on
      our results, we propose an additional step in the mechanism of action of the Cry8
      toxin and elucidate the function of the associated DNA as well as the importance
      of the removal of this DNA for the insecticidal activity of the toxin. 

PMID- 24324686
TI  - Tumor necrosis factor -alpha, interleukin-10, intercellular and vascular adhesion
      molecules are possible biomarkers of disease severity in complicated Plasmodium
      vivax isolates from Pakistan.
AB  - BACKGROUND: Cytokine-mediated endothelial activation pathway is a known mechanism
      of pathogenesis employed by Plasmodium falciparum to induce severe disease
      symptoms in human host. Though considered benign, complicated cases of Plasmodium
      vivax are being reported worldwide and from Pakistan. It has been hypothesized
      that P.vivax utilizes similar mechanism of pathogenesis, as that of P.falciparum
      for manifestations of severe malaria. Therefore, the main objective of this study
      was to characterize the role of cytokines and endothelial activation markers in
      complicated Plasmodium vivax isolates from Pakistan. METHODS AND PRINCIPLE
      FINDINGS: A case control study using plasma samples from well-characterized
      groups suffering from P.vivax infection including uncomplicated cases (n=100),
      complicated cases (n=82) and healthy controls (n=100) were investigated. Base
      line levels of Tumor necrosis factor-alpha (TNF-alpha), Interleukin-6 (IL-6),
      Interleukin-10 (IL-10), Intercellular adhesion molecule-1 (ICAM-1), Vascular
      adhesion molecule-1(VCAM-1) and E-selectin were measured by ELISA. Correlation of
      cytokines and endothelial activation markers was done using Spearman's
      correlation analysis. Furthermore, significance of these biomarkers as indicators
      of disease severity was also analyzed. The results showed that TNF-alpha, IL-10,
      ICAM-1and VCAM-1 were 3-fold, 3.7 fold and 2 fold increased between uncomplicated
      and complicated cases. Comparison of healthy controls with uncomplicated cases
      showed no significant difference in TNF-alpha concentrations while IL-6, IL-10,
      ICAM-1, VCAM-1 and E-selectin were found to be elevated respectively. In
      addition, significant positive correlation was observed between TNF-alpha and IL
      10/ ICAM-1, IL-6 and IL-10, ICAM-1 and VCAM-1.A Receiver operating curve (ROC)
      was generated which showed that TNF-alpha, IL-10, ICAM-1 and VCAM-1 were the best
      individual predictors of complicated P.vivax malaria. CONCLUSION: The results
      suggest that though endothelial adhesion molecules are inducible by pro
      inflammatory cytokine TNF-alpha, however, cytokine-mediated endothelial
      activation pathway is not clearly demonstrated as a mechanism of pathogenesis in
      complicated P.vivax malaria cases from Pakistan.

PMID- 24324688
TI  - Alpha-actinin is a new type of house dust mite allergen.
AB  - Main indoor allergens for humans are from house dust mites. There are more than
      30 allergens in Dermatophagoides farinae but only fourteen allergens have been
      identified from this mite including Der f 1-3, 6, 7, 10, 11, 13-18, and 22. A
      native allergen protein (Der f 24, 90 kDa) was purified from D. farinae by gel
      filtration and anionic exchange liquid chromatography combined with IgE
      immunodetection. Its primary structure was determined by Edman degradation, mass
      spectrometry analysis and cDNA cloning. Enzyme-linked immunosorbent assay
      inhibition tests (ELISA-IT), immunoblots, basophil activation test (BAT) and skin
      prick test (SPT) were performed to evaluate the allergenicity. It was identified
      as an alpha (alpha)-actinin containing a CaM-like domain with EF-hand motifs. Der
      f 24 reacted to sera from 85.4% (35/41) of patients on western blot analysis. It
      reduced ~20% sera IgE reactivity to D. farinae extracts on a competitive ELISA.
      Eighty percent (8/10) of patients with D. farinae allergy showed positive
      reactions to Der f 24 in skin prick test. The expression of CD63 on basophils
      from patients was up-regulated by Der f 24 by ~5.4-fold. Alpha-actinin was
      identified as a new type of house dust mite allergen. To the best of our
      knowledge, this is the first report of alpha-actinin as an allergen. 

PMID- 24324687
TI  - mRNA localization mechanisms in Trypanosoma cruzi.
AB  - Asymmetric mRNA localization is a sophisticated tool for regulating and
      optimizing protein synthesis and maintaining cell polarity. Molecular mechanisms
      involved in the regulated localization of transcripts are widespread in higher
      eukaryotes and fungi, but not in protozoa. Trypanosomes are ancient eukaryotes
      that branched off early in eukaryote evolution. We hypothesized that these
      organisms would have basic mechanisms of mRNA localization. FISH assays with
      probes against transcripts coding for proteins with restricted distributions
      showed a discrete localization of the mRNAs in the cytoplasm. Moreover, cruzipain
      mRNA was found inside reservosomes suggesting new unexpected functions for this
      vacuolar organelle. Individual mRNAs were also mobilized to RNA granules in
      response to nutritional stress. The cytoplasmic distribution of these transcripts
      changed with cell differentiation, suggesting that localization mechanisms might
      be involved in the regulation of stage-specific protein expression. Transfection
      assays with reporter genes showed that, as in higher eukaryotes, 3'UTRs were
      responsible for guiding mRNAs to their final location. Our results strongly
      suggest that Trypanosoma cruzi have a core, basic mechanism of mRNA localization.
      This kind of controlled mRNA transport is ancient, dating back to early eukaryote
      evolution. 

PMID- 24324689
TI  - The importance of perceptual experience in the esthetic appreciation of the body.
AB  - Several studies suggest that sociocultural models conveying extreme thinness as
      the widespread ideal of beauty exert an important influence on the perceptual and
      emotional representation of body image. The psychological mechanisms underlying
      such environmental influences, however, are unclear. Here, we utilized a
      perceptual adaptation paradigm to investigate how perceptual experience modulates
      body esthetic appreciation. We found that the liking judgments of round bodies
      increased or decreased after brief exposure to round or thin bodies,
      respectively. No change occurred in the liking judgments of thin bodies. The
      results suggest that perceptual experience may shape our esthetic appreciation to
      favor more familiar round body figures. Importantly, individuals with more
      deficits in interoceptive awareness were less prone to increase their liking
      ratings of round bodies after exposure, suggesting a specific risk factor for the
      susceptibility to the influence of the extreme thin vs. round body ideals of
      beauty portrayed by the media. 

PMID- 24324690
TI  - Small molecule proprotein convertase inhibitors for inhibition of embryo
      implantation.
AB  - Uterine proprotein convertase (PC) 6 plays a critical role in embryo implantation
      and is pivotal for pregnancy establishment. Inhibition of PC6 may provide a novel
      approach for the development of non-hormonal and female-controlled
      contraceptives. We investigated a class of five synthetic non-peptidic small
      molecule compounds that were previously reported as potent inhibitors of furin,
      another PC member. We examined (i) the potency of these compounds in inhibiting
      PC6 activity in vitro; (ii) their binding modes in the PC6 active site in silico;
      (iii) their efficacy in inhibiting PC6-dependent cellular processes essential for
      embryo implantation using human cell-based models. All five compounds showed
      potent inhibition of PC6 activity in vitro, and in silico docking demonstrated
      that these inhibitors could adopt a similar binding mode in the PC6 active site.
      However, when these compounds were tested for their inhibition of decidualization
      of primary human endometrial stromal cells, a PC6-dependent cellular process
      critical for embryo implantation, only one (compound 1o) showed potent
      inhibition. The lack of activity in the cell-based assay may reflect the
      inability of the compounds to penetrate the cell membrane. Because compound's
      lipophilicity is linked to cell penetration, a measurement of lipophilicity
      (logP) was calculated for each compound. Compound 1o is unique as it appears the
      most lipophilic among the five compounds. Compound 1o also inhibited another
      crucial PC6-dependent process, the attachment of human trophoblast spheroids to
      endometrial epithelial cells (a model for human embryo attachment). We thus
      identified compound 1o as a potent small molecule PC6 inhibitor with
      pharmaceutical potential to inhibit embryo implantation. Our findings also
      highlight that human cell-based functional models are vital to complement the
      biochemical and in silico analyses in the selection of promising drug candidates.
      Further investigations for compound 1o are warranted in animal models to test its
      utility as an implantation-inhibiting contraceptive drug. 

PMID- 24324691
TI  - Delayed effect of craniotomy on experimental seizures in rats.
AB  - Neurosurgical therapeutic interventions include components that are presumed to
      be therapeutically inert, such as craniotomy and electrode implantation. Because
      these procedures may themselves exert neuroactive actions, with anecdotal
      evidence suggesting that craniotomy and electrode placement may have a
      particularly significant impact on epileptic seizures, the importance of their
      inclusion in sham control groups has become more compelling. Here we set out to
      test the hypothesis that craniotomy alone is sufficient to alter experimental
      seizures in rats. We tested adult male rats for seizures evoked by
      pentylenetetrazole (70 mg/kg) between 3 and 20 days following placement of
      bilateral craniotomies (either 2.5 or 3.5 mm in diameter) in the parietal bone of
      the skull, without penetrating the dura. Control (sham-operated) animals
      underwent anesthesia and surgery without craniotomy. We found that craniotomy
      significantly decreased the severity of experimental seizures on postoperative
      days 3, 6, and 10; this effect was dependent on the size of craniotomy. Animals
      with craniotomies returned to control seizure severity by 20 days post
      craniotomy. These data support the hypothesis that damage to the skull is
      sufficient to cause a significant alteration in seizure susceptibility over an
      extended postoperative period, and indicate that this damage should not be
      considered neurologically inert. 

PMID- 24324692
TI  - T cells at the site of autoimmune inflammation show increased potential for
      trogocytosis.
AB  - CD4+ T cells acquire membrane fragments from antigen-presenting-cells via a
      process termed trogocytosis. Identifying which CD4+ T cells undergo trogocytosis
      in co-culture with Ag-loaded APC can enrich for antigen-reactive T cells without
      knowledge of their fine specificity or cytokine-production profiles. We sought to
      assess the suitability of this method to identify disease relevant effector and
      regulatory T cells during autoimmune inflammation. Trogocytosis efficiently
      identified MBP-reactive T cells in vitro and ex-vivo following immunization.
      However, Foxp3+ regulatory T cells constitutively displayed a higher rate of
      trogocytosis than their Foxp3- counterparts which limits the potential of
      trogocytosis to identify antigen-reactive Treg cells. During inflammation a
      locally elevated rate of trogocytosis (seen in both effector and regulatory T
      cells isolated from the inflamed CNS) precludes the use of trogocytosis as a
      measure of antigenic reactivity among cells taken from inflammatory sites. Our
      results indicate trogocytosis detection can enrich for Ag-reactive conventional T
      cells in the periphery but is limited in its ability to identify Ag-reactive Treg
      or T effector cells at sites of inflammation. Increased trogocytosis potential at
      inflammatory sites also draws into the question the biological significance of
      this phenomenon during inflammation, in Treg mediated suppression and for the
      maintenance of tolerance in health and disease. 

PMID- 24324694
TI  - Effects of different grazing intensities on grassland production in China: a meta
      analysis.
AB  - BACKGROUND: Grazing is one of the main grassland disturbances in China, and it is
      essential to quantitatively evaluate the effects of different grazing intensities
      on grassland production for grassland carbon budget and sustainable use. METHODS:
      A meta-analysis was conducted to reveal general response patterns of grassland
      production to grazing in China. We used weighted log response ratio to assess the
      effect size, and 95% confidence intervals to give a sense of the precision of the
      estimate. Grazing effects were estimated as a percentage change relative to
      control (%). RESULTS: A total of 48 studies, including 251 data sets, were
      included in the meta-analysis. Grazing significantly decreased total biomass by
      58.34% (95% CI: -72.04%~-37.94%, CI: Confidence Interval), increased root/shoot
      ratio by 30.58% and decreased litter by 51.41% (95% CI: -63.31%~-35.64%).
      Aboveground biomass and belowground biomass decreased significantly by 42.77%
      (95% CI: -48.88%~-35.93%) and 23.13% (95% CI: -39.61%~-2.17%), respectively.
      However, biomass responses were dependent on grazing intensity and environmental
      conditions. Percentage changes in aboveground biomass to grazing showed a
      quadratic relationship with precipitation in light grazing intensity treatment
      and a linear relationship in moderate and heavy grazing intensity treatment, but
      did not change with temperature. Grazing effects on belowground biomass did not
      change with precipitation or temperature. Compared to the global average value,
      grazing had greater negative effects on grassland production in China.
      CONCLUSIONS: Grazing has negative effects on grassland biomass and the grazing
      effects change with environmental conditions and grazing intensity, therefore
      flexible rangeland management tactics that suit local circumstances are necessary
      to take into consideration for balancing the demand of grassland utilization and
      conservation.

PMID- 24324695
TI  - Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the
      perinatal lamb model of RSV.
AB  - Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in
      infants and children worldwide. There are currently no licensed vaccines or
      effective antivirals. The lack of a vaccine is partly due to increased caution
      following the aftermath of a failed clinical trial of a formalin-inactivated RSV
      vaccine (FI-RSV) conducted in the 1960's that led to enhanced disease,
      necessitating hospitalization of 80% of vaccine recipients and resulting in two
      fatalities. Perinatal lamb lungs are similar in size, structure and physiology to
      those of human infants and are susceptible to human strains of RSV that induce
      similar lesions as those observed in infected human infants. We sought to
      determine if perinatal lambs immunized with FI-RSV would develop key features of
      vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized
      at 3-5 days of age with FI-RSV followed two weeks later by RSV infection. The FI
      RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced
      disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung,
      and increased infiltration of peribronchiolar and perivascular lymphocytes
      compared to lambs either undergoing an acute RSV infection or naive controls; all
      features of RSV vaccine-enhanced disease. These results represent a first step
      proof-of-principle demonstration that the lamb can develop altered responses to
      RSV following FI-RSV vaccination. The lamb model may be useful for future
      mechanistic studies as well as the assessment of RSV vaccines designed for
      infants. 

PMID- 24324693
TI  - Treatment response in Kawasaki disease is associated with sialylation levels of
      endogenous but not therapeutic intravenous immunoglobulin G.
AB  - OBJECTIVES: Although intravenous immunoglobulin (IVIG) is highly effective in
      Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are
      treatment-resistant, manifesting a higher rate of coronary artery aneurysms.
      Murine models suggest that alpha2-6-linked sialic acid (alpha2-6Sia) content of
      IVIG is critical for suppressing inflammation. However, pro-inflammatory states
      also up-regulate endogenous levels of beta-galactoside:alpha2-6 sialyltransferase
      I (ST6Gal-I), the enzyme that catalyzes addition of alpha2-6Sias to N-glycans. We
      asked whether IVIG failures correlated with levels of alpha2-6Sia on infused IVIG
      or on the patient's own endogenous IgG. METHODS: We quantified levels of alpha2
      6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant
      KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient
      whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I
      levels were measured by ELISA. RESULTS: There was no consistent difference in
      median sialylation levels of infused IVIG between groups. However, alpha2-6Sia
      levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in
      serum from IVIG-resistant KD subjects were lower than in responsive subjects at
      both pre-treatment and one-year time points (p <0.001, respectively).
      CONCLUSIONS: Our data indicate sialylation levels of therapeutic IVIG are
      unrelated to treatment response in KD. Rather, lower sialylation of endogenous
      IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy
      resistance. These differences were stable over time, suggesting a genetic basis.
      Because IVIG-resistance increases risk of coronary artery aneurysms, our findings
      have important implications for the identification and treatment of such
      individuals.

PMID- 24324696
TI  - Genetic variability of the neogregarine Apicystis bombi, an etiological agent of
      an emergent bumblebee disease.
AB  - The worldwide spread of diseases is considered a major threat to biodiversity and
      a possible driver of the decline of pollinator populations, particularly when
      novel species or strains of parasites emerge. Previous studies have suggested
      that populations of introduced European honeybee (Apis mellifera) and bumblebee
      species (Bombus terrestris and Bombus ruderatus) in Argentina share the
      neogregarine parasite Apicystis bombi with the native bumblebee (Bombus
      dahlbomii). In this study we investigated whether A. bombi is acting as an
      emergent parasite in the non-native populations. Specifically, we asked whether
      A. bombi, recently identified in Argentina, was introduced by European, non
      native bees. Using ITS1 and ITS2 to assess the parasite's intraspecific genetic
      variation in bees from Argentina and Europe, we found a largely unstructured
      parasite population, with only 15% of the genetic variation being explained by
      geographic location. The most abundant haplotype in Argentina (found in all 9
      specimens of non-native species) was identical to the most abundant haplotype in
      Europe (found in 6 out of 8 specimens). Similarly, there was no evidence of
      structuring by host species, with this factor explaining only 17% of the genetic
      variation. Interestingly, parasites in native Bombus ephippiatus from Mexico were
      genetically distant from the Argentine and European samples, suggesting that
      sufficient variability does exist in the ITS region to identify continent-level
      genetic structure in the parasite. Thus, the data suggest that A. bombi from
      Argentina and Europe share a common, relatively recent origin. Although our data
      did not provide information on the direction of transfer, the absence of genetic
      structure across space and host species suggests that A. bombi may be acting as
      an emergent infectious disease across bee taxa and continents. 

PMID- 24324697
TI  - Hyperspectral sensing of disease stress in the Caribbean reef-building coral,
      Orbicella faveolata - perspectives for the field of coral disease monitoring.
AB  - The effectiveness of management plans developed for responding to coral disease
      outbreaks is limited due to the lack of rapid methods of disease diagnosis. In
      order to fulfill current management guidelines for responding to coral disease
      outbreaks, alternative methods that significantly reduce response time must be
      developed. Hyperspectral sensing has been used by various groups to characterize
      the spectral signatures unique to asymptomatic and bleached corals. The 2010
      combined bleaching and Caribbean yellow band disease outbreak in Puerto Rico
      provided a unique opportunity to investigate the spectral signatures associated
      with bleached and Caribbean yellow band-diseased colonies of Orbicella faveolata
      for the first time. Using derivative and cluster analyses of hyperspectral
      reflectance data, the present study demonstrates the proof of concept that
      spectral signatures can be used to differentiate between coral disease states.
      This method enhanced predominant visual methods of diagnosis by distinguishing
      between different asymptomatic conditions that are identical in field
      observations and photographic records. The ability to identify disease-affected
      tissue before lesions become visible could greatly reduce response times to coral
      disease outbreaks in monitoring efforts. Finally, spectral signatures associated
      with the poorly understood Caribbean yellow band disease are presented to guide
      future research on the role of pigments in the etiology. 

PMID- 24324699
TI  - The role of dynamic susceptibility contrast-enhanced perfusion MR imaging in
      differentiating between infectious and neoplastic focal brain lesions: results
      from a cohort of 100 consecutive patients.
AB  - BACKGROUND AND PURPOSE: Differentiating between infectious and neoplastic focal
      brain lesions that are detected by conventional structural magnetic resonance
      imaging (MRI) may be a challenge in routine practice. Brain perfusion-weighted
      MRI (PWI) may be employed as a complementary non-invasive tool, providing
      relevant data on hemodynamic parameters, such as the degree of angiogenesis of
      lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR
      imaging (DSC-MRI) to differentiate between infectious and neoplastic brain
      lesions by investigating brain microcirculation changes. MATERIALS AND METHODS:
      DSC-MRI perfusion studies of one hundred consecutive patients with non-cortical
      neoplastic (n = 54) and infectious (n = 46) lesions were retrospectively
      assessed. MRI examinations were performed using a 1.5-T scanner. A preload of
      paramagnetic contrast agent (gadolinium) was administered 30 seconds before
      acquisition of dynamic images, followed by a standard dose 10 seconds after
      starting imaging acquisitions. The relative cerebral blood volume (rCBV) values
      were determined by calculating the regional cerebral blood volume in the solid
      areas of lesions, normalized to that of the contralateral normal-appearing white
      matter. Discriminant analyses were performed to determine the cutoff point of
      rCBV values that would allow the differentiation of neoplastic from infectious
      lesions and to assess the corresponding diagnostic performance of rCBV when using
      this cutoff value. RESULTS: Neoplastic lesions had higher rCBV values (4.28+/
      2.11) than infectious lesions (0.63+/-0.49) (p<0.001). When using an rCBV value
      <1.3 as the parameter to define infectious lesions, the sensitivity of the method
      was 97.8% and the specificity was 92.6%, with a positive predictive value of
      91.8%, a negative predictive value of 98.0%, and an accuracy of 95.0%.
      CONCLUSION: PWI is a useful complementary tool in distinguishing between
      infectious and neoplastic brain lesions; an elevated discriminatory value for
      diagnosis of infectious brain lesions was observed in this sample of patients
      when the rCBV cutoff value was set to 1.3.

PMID- 24324698
TI  - Telmisartan ameliorates fibrocystic liver disease in an orthologous rat model of
      human autosomal recessive polycystic kidney disease.
AB  - Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys
      which are massively enlarged due to multiple cysts, hypertension, and congenital
      hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The
      PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts
      caused by stimulated cellular proliferation in the renal tubules and hepatic bile
      duct epithelia, with interstitial fibrosis developed in the liver. We previously
      reported that a peroxisome proliferator activated receptor (PPAR)-gamma full
      agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an
      angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and
      shows partial PPAR-gamma agonist activity. It also has nephroprotective activity
      in diabetes and renal injury and prevents the effects of drug-induced
      hepatotoxicity and hepatic fibrosis. In the present study, we determined whether
      telmisartan ameliorates progression of polycystic kidney and fibrocystic liver
      disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats
      were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20
      weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and
      +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase
      and urea nitrogen were unaffected by telmisartan treatment. There was no effect
      on kidney disease progression, but liver weight relative to body weight, liver
      cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-beta, and
      the number of Ki67- and TGF-beta-positive interstitial cells in the liver were
      significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan
      ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition
      of signaling cascades responsible for cellular proliferation and interstitial
      fibrosis in PCK rats. The present results support the potential therapeutic use
      of ARBs for the treatment of fibrocystic liver disease in ARPKD patients. 

PMID- 24324700
TI  - The voltage-dependent anion selective channel 1 (VDAC1) topography in the
      mitochondrial outer membrane as detected in intact cell.
AB  - Voltage-Dependent Anion selective Channel maintains the permeability of the outer
      mitochondrial membrane and is relevant in bioenergetic metabolism and apoptosis.
      The structure of the protein was shown to be a beta-barrel formed by 19 strands.
      The topology or sideness of the pore has been predicted with various approaches
      but a general consensus was never reached. This is an important issue since VDAC
      is considered receptor of Hexokinase and Bcl-2. We fused at VDAC1 C-terminus two
      tags separated by a caspase cleavage site. Activation in cellulo of caspases was
      used to eventually separate the two reporters. This experiment did not require
      the isolation of mitochondria and limited the possibility of outer membrane
      rupture due to similar procedures. Our results show that the C-terminus end of
      VDAC faces the mitochondrial inter-membrane space. 

PMID- 24324701
TI  - Diabetes in cystic fibrosis: multicenter screening results based on current
      guidelines.
AB  - BACKGROUND: Published estimates on age-dependent frequency of diabetes in cystic
      fibrosis (CF) vary widely, and are based mostly on older data. However, CF
      treatment and prevention of comorbidities changed over recent years. In many
      studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line
      with current guideline recommendations. Therefore, we evaluated age-dependent
      occurrence of glucose abnormalities and associated risk factors in CF patients
      who participated in a multicenter screening program using oral glucose tolerance
      tests (OGTT). METHODS: Between 2001 and 2010, 43 specialized CF centers from
      Germany and Austria serially performed 5,179 standardized OGTTs in 1,658
      clinically stable, non-pregnant CF patients with no prior steroid medication or
      lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG),
      impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD)
      diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards
      models were created to elucidate the influence of sex or underweight. RESULTS: At
      baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of
      patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at
      age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of
      patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI
      1.23-10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22-3.98] times
      higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11-1.71]) and
      IFG+IGT (1.43 [1.11-1.83]), and in males also for DGT (1.49 [1.09-2.04]).
      CONCLUSIONS/SIGNIFICANCE: If confirmation of diabetes by a second test is
      required, as recommended in current guidelines, age at CFRD diagnosis was higher
      compared to most previous studies. However, known risk factors for glucose
      abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test
      is important for a consistent diagnosis of CFRD.

PMID- 24324702
TI  - Variation in the morphology of Bacillus mycoides due to applied force and
      substrate structure.
AB  - Response to mechanical force is a well characterised phenomenon in eukaryotic
      organisms, helping to organise multicellular structures. Mechanotactic responses
      have only rarely been observed in prokaryotic taxa. This work reports on a
      morphological change due to variations in applied force and surface structure by
      Bacillus mycoides Flugge. B. mycoides is a ubiquitous soil organism well known
      among microbiologists for its characteristic spreading colony morphology. An
      apparent mechanotactic response is elicited by physical deformation of the gel
      media on which B.mycoides is growing, including applied forces of compression or
      tension. Variations in the surface such as curvature produced by casting the agar
      gel in the presence of curved objects also elicited the change. The morphological
      change in B.mycoides colonies associated with the application of force manifests
      as a pattern of parallel rhizoid filaments perpendicular to compressing force and
      parallel to stretching force in the agar medium. The phenomenon is most clearly
      demonstrated by reversible changes in the orientation of B. mycoides filaments
      during time-lapse microscopy. 

PMID- 24324703
TI  - Soyasaponin I improved neuroprotection and regeneration in memory deficient model
      rats.
AB  - Soy (Glycine Max Merr, family Leguminosae) has been reported to possess anti
      cancer, anti-lipidemic, estrogen-like, and memory-enhancing effects. We
      investigated the memory-enhancing effects and the underlying mechanisms of
      soyasaponin I (soya-I), a major constituent of soy. Impaired learning and memory
      were induced by injecting ibotenic acid into the entorhinal cortex of adult rat
      brains. The effects of soya-I were evaluated by measuring behavioral tasks and
      neuronal regeneration of memory-deficient rats. Oral administration of soya-I
      exhibited significant memory-enhancing effects in the passive avoidance, Y-maze,
      and Morris water maze tests. Soya-Iota also increased BrdU incorporation into the
      dentate gyrus and the number of cell types (GAD67, ChAT, and VGluT1) in the
      hippocampal region of memory-deficient rats, whereas the number of reactive
      microglia (OX42) decreased. The mechanism underlying memory improvement was
      assessed by detecting the differentiation and proliferation of neural precursor
      cells (NPCs) prepared from the embryonic hippocampus (E16) of timed-pregnant
      Sprague-Dawley rats using immunocytochemical staining and immunoblotting
      analysis. Addition of soya-Iota in the cultured NPCs significantly elevated the
      markers for cell proliferation (Ki-67) and neuronal differentiation (NeuN, TUJ1,
      and MAP2). Finally, soya-I increased neurite lengthening and the number of
      neurites during the differentiation of NPCs. Soya-Iota may improve hippocampal
      learning and memory impairment by promoting proliferation and differentiation of
      NPCs in the hippocampus through facilitation of neuronal regeneration and
      minimization of neuro-inflammation. 

PMID- 24324704
TI  - Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with
      antituberculosis treatment.
AB  - RATIONALE: Biomarkers associated with response to therapy in tuberculosis could
      have broad clinical utility. We postulated that the frequency of Mycobacterium
      tuberculosis (Mtb) specific CD8(+) T cells, by virtue of detecting intracellular
      infection, could be a surrogate marker of response to therapy and would decrease
      during effective antituberculosis treatment. OBJECTIVES: We sought to determine
      the relationship of Mtb specific CD4(+) T cells and CD8(+) T cells with duration
      of antituberculosis treatment. MATERIALS AND METHODS: We performed a prospective
      cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected
      Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed
      pulmonary TB at the onset of antituberculosis treatment and the Mtb specific
      CD4(+) and CD8(+) T cell responses to ESAT-6 and CFP-10 were measured by IFN
      gamma ELISPOT at enrollment, week 8 and 24. RESULTS: There was a significant
      difference in the Mtb specific CD8(+) T response, but not the CD4(+) T cell
      response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early
      difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated
      Mtb specific CD8(+) T cell response decreased by 58%. In contrast, there was no
      significant difference in the Mtb specific CD4(+) T cell during the treatment.
      The Mtb specific CD4(+) T cell response, but not the CD8(+) response, was
      negatively impacted by the body mass index. CONCLUSIONS: Our data provide
      evidence that the Mtb specific CD8(+) T cell response declines with
      antituberculosis treatment and could be a surrogate marker of response to
      therapy. Additional research is needed to determine if the Mtb specific CD8(+) T
      cell response can detect early treatment failure, relapse, or to predict disease
      progression.

PMID- 24324705
TI  - Meclozine facilitates proliferation and differentiation of chondrocytes by
      attenuating abnormally activated FGFR3 signaling in achondroplasia.
AB  - Achondroplasia (ACH) is one of the most common skeletal dysplasias with short
      stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast
      growth factor receptor 3. We used the drug repositioning strategy to identify an
      FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We
      found that meclozine, an anti-histamine drug that has long been used for motion
      sickness, facilitates chondrocyte proliferation and mitigates loss of
      extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine
      also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS
      2/8) cells that were infected with lentivirus expressing constitutively active
      mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing
      SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally
      suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and
      -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2
      mediated longitudinal growth inhibition of embryonic tibia in bone explant
      culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant
      culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3
      signaling disclosed that meclozine downregulates phosphorylation of ERK but not
      of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of
      RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK,
      which suggests that meclozine downregulates the FGFR3 signaling by possibly
      attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a
      potent inhibitor of the FGFR3 signaling throughout our experiments, and found
      that meclozine was as efficient as CNP in attenuating the abnormal FGFR3
      signaling. We propose that meclozine is a potential therapeutic agent for
      treating ACH and other FGFR3-related skeletal dysplasias. 

PMID- 24324706
TI  - Hoxb4 overexpression in CD4 memory phenotype T cells increases the central memory
      population upon homeostatic proliferation.
AB  - Memory T cell populations allow a rapid immune response to pathogens that have
      been previously encountered and thus form the basis of success in vaccinations.
      However, the molecular pathways underlying the development and maintenance of
      these cells are only starting to be unveiled. Memory T cells have the capacity to
      self renew as do hematopoietic stem cells, and overlapping gene expression
      profiles suggested that these cells might use the same self-renewal pathways. The
      transcription factor Hoxb4 has been shown to promote self-renewal divisions of
      hematopoietic stem cells resulting in an expansion of these cells. In this study
      we investigated whether overexpression of Hoxb4 could provide an advantage to CD4
      memory phenotype T cells in engrafting the niche of T cell deficient mice
      following adoptive transfer. Competitive transplantation experiments demonstrated
      that CD4 memory phenotype T cells derived from mice transgenic for Hoxb4
      contributed overall less to the repopulation of the lymphoid organs than wild
      type CD4 memory phenotype T cells after two months. These proportions were
      relatively maintained following serial transplantation in secondary and tertiary
      mice. Interestingly, a significantly higher percentage of the Hoxb4 CD4 memory
      phenotype T cell population expressed the CD62L and Ly6C surface markers,
      characteristic for central memory T cells, after homeostatic proliferation. Thus
      Hoxb4 favours the maintenance and increase of the CD4 central memory phenotype T
      cell population. These cells are more stem cell like and might eventually lead to
      an advantage of Hoxb4 T cells after subjecting the cells to additional rounds of
      proliferation. 

PMID- 24324707
TI  - Chronic intermittent hypoxia exerts CNS region-specific effects on rat microglial
      inflammatory and TLR4 gene expression.
AB  - Intermittent hypoxia (IH) during sleep is a hallmark of sleep apnea, causing
      significant neuronal apoptosis, and cognitive and behavioral deficits in CNS
      regions underlying memory processing and executive functions. IH-induced
      neuroinflammation is thought to contribute to cognitive deficits after IH. In the
      present studies, we tested the hypothesis that IH would differentially induce
      inflammatory factor gene expression in microglia in a CNS region-dependent
      manner, and that the effects of IH would differ temporally. To test this
      hypothesis, adult rats were exposed to intermittent hypoxia (2 min intervals of
      10.5% O2) for 8 hours/day during their respective sleep cycles for 1, 3 or 14
      days. Cortex, medulla and spinal cord tissues were dissected, microglia were
      immunomagnetically isolated and mRNA levels of the inflammatory genes iNOS, COX
      2, TNFalpha, IL-1beta and IL-6 and the innate immune receptor TLR4 were compared
      to levels in normoxia. Inflammatory gene expression was also assessed in tissue
      homogenates (containing all CNS cells). We found that microglia from different
      CNS regions responded to IH differently. Cortical microglia had longer lasting
      inflammatory gene expression whereas spinal microglial gene expression was rapid
      and transient. We also observed that inflammatory gene expression in microglia
      frequently differed from that in tissue homogenates from the same region,
      indicating that cells other than microglia also contribute to IH-induced
      neuroinflammation. Lastly, microglial TLR4 mRNA levels were strongly upregulated
      by IH in a region- and time-dependent manner, and the increase in TLR4 expression
      appeared to coincide with timing of peak inflammatory gene expression, suggesting
      that TLR4 may play a role in IH-induced neuroinflammation. Together, these data
      indicate that microglial-specific neuroinflammation may play distinct roles in
      the effects of intermittent hypoxia in different CNS regions. 

PMID- 24324708
TI  - A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits
      MERS-CoV infection and induces strong neutralizing antibody responses:
      implication for developing therapeutics and vaccines.
AB  - An emerging respiratory infectious disease with high mortality, Middle East
      respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was
      first reported in 2012 in Saudi Arabia and has now spread to eight countries.
      Development of effective therapeutics and vaccines is crucial to save lives and
      halt the spread of MERS-CoV. Here, we show that a recombinant protein containing
      a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding
      domain (RBD: residues 367-606) of MERS-CoV spike (S) protein fused with human IgG
      Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of
      transfected 293T cells. The purified S377-588-Fc protein efficiently binds to
      dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited
      MERS-CoV infection, suggesting its potential to be further developed as a
      therapeutic modality for treating MERS-CoV infection and saving the patients'
      lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice
      strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4
      receptor and effectively neutralizes MERS-CoV infection. These findings indicate
      that this truncated RBD protein shows promise for further development as an
      effective and safe vaccine for the prevention of MERS-CoV infection. 

PMID- 24324709
TI  - Photic and pineal modulation of food anticipatory circadian activity rhythms in
      rodents.
AB  - Restricted daily feeding schedules entrain circadian oscillators that generate
      food anticipatory activity (FAA) rhythms in nocturnal rodents. The location of
      food-entrainable oscillators (FEOs) necessary for FAA remains uncertain. The most
      common procedure for inducing circadian FAA is to limit food access to a few
      hours in the middle of the light period, when activity levels are normally low.
      Although light at night suppresses activity (negative masking) in nocturnal
      rodents, it does not prevent the expression of daytime FAA. Nonetheless, light
      could reduce the duration or magnitude of FAA. If so, then neural or genetic
      ablations designed to identify components of the food-entrainable circadian
      system could alter the expression of FAA by affecting behavioral responses to
      light. To assess the plausibility of light as a potential mediating variable in
      studies of FAA mechanisms, we quantified FAA in rats and mice alternately
      maintained in a standard full photoperiod (12h of light/day) and in a skeleton
      photoperiod (two 60 min light pulses simulating dawn and dusk). In both species,
      FAA was significantly and reversibly enhanced in the skeleton photoperiod
      compared to the full photoperiod. In a third experiment, FAA was found to be
      significantly attenuated in rats by pinealectomy, a procedure that has been
      reported to enhance some effects of light on behavioral circadian rhythms. These
      results indicate that procedures affecting behavioral responses to light can
      significantly alter the magnitude of food anticipatory rhythms in rodents. 

PMID- 24324710
TI  - A nonsense mutation in the IKBKG gene in mares with incontinentia pigmenti.
AB  - Ectodermal dysplasias (EDs) are a large and heterogeneous group of hereditary
      disorders characterized by abnormalities in structures of ectodermal origin.
      Incontinentia pigmenti (IP) is an ED characterized by skin lesions evolving over
      time, as well as dental, nail, and ocular abnormalities. Due to X-linked dominant
      inheritance IP symptoms can only be seen in female individuals while affected
      males die during development in utero. We observed a family of horses, in which
      several mares developed signs of a skin disorder reminiscent of human IP.
      Cutaneous manifestations in affected horses included the development of pruritic,
      exudative lesions soon after birth. These developed into wart-like lesions and
      areas of alopecia with occasional wooly hair re-growth. Affected horses also had
      streaks of darker and lighter coat coloration from birth. The observation that
      only females were affected together with a high number of spontaneous abortions
      suggested an X-linked dominant mechanism of transmission. Using next generation
      sequencing we sequenced the whole genome of one affected mare. We analyzed the
      sequence data for non-synonymous variants in candidate genes and found a
      heterozygous nonsense variant in the X-chromosomal IKBKG gene (c.184C>T;
      p.Arg62*). Mutations in IKBKG were previously reported to cause IP in humans and
      the homologous p.Arg62* variant has already been observed in a human IP patient.
      The comparative data thus strongly suggest that this is also the causative
      variant for the observed IP in horses. To our knowledge this is the first large
      animal model for IP. 

PMID- 24324711
TI  - A built-in strategy to mitigate transgene spreading from genetically modified
      corn.
AB  - Transgene spreading is a major concern in cultivating genetically modified (GM)
      corn. Cross-pollination may cause the spread of transgenes from GM cornfields to
      conventional fields. Occasionally, seed lot contamination, volunteers, mixing
      during sowing, harvest, and trade can also lead to transgene escape. Obviously,
      new biological confinement technologies are highly desired to mitigate transgene
      spreading in addition to physical separation and isolation methods. In this
      study, we report the development of a built-in containment method to mitigate
      transgene spreading in corn. In this method, an RNAi cassette for suppressing the
      expression of the nicosulfuron detoxifying enzyme CYP81A9 and an expression
      cassette for the glyphosate tolerant 5-enolpyruvylshikimate-3-phosphate synthase
      (EPSPS) gene G10 were constructed and transformed into corn via Agrobacterium
      mediated transformation. The GM corn plants that were generated were found to be
      sensitive to nicosulfuron but resistant to glyphosate, which is exactly the
      opposite of conventional corn. Field tests demonstrated that GM corn plants with
      silenced CYP81A9 could be killed by applying nicosulfuron at 40 g/ha, which is
      the recommended dose for weed control in cornfields. This study suggests that
      this built-in containment method for controlling the spread of corn transgenes is
      effective and easy to implement. 

PMID- 24324712
TI  - Agreement of mammographic measures of volumetric breast density to MRI.
AB  - BACKGROUND: Clinical scores of mammographic breast density are highly subjective.
      Automated technologies for mammography exist to quantify breast density
      objectively, but the technique that most accurately measures the quantity of
      breast fibroglandular tissue is not known. PURPOSE: To compare the agreement of
      three automated mammographic techniques for measuring volumetric breast density
      with a quantitative volumetric MRI-based technique in a screening population.
      MATERIALS AND METHODS: Women were selected from the UCSF Medical Center screening
      population that had received both a screening MRI and digital mammogram within
      one year of each other, had Breast Imaging Reporting and Data System (BI-RADS)
      assessments of normal or benign finding, and no history of breast cancer or
      surgery. Agreement was assessed of three mammographic techniques (Single-energy X
      ray Absorptiometry [SXA], Quantra, and Volpara) with MRI for percent
      fibroglandular tissue volume, absolute fibroglandular tissue volume, and total
      breast volume. RESULTS: Among 99 women, the automated mammographic density
      techniques were correlated with MRI measures with R(2) values ranging from 0.40
      (log fibroglandular volume) to 0.91 (total breast volume). Substantial agreement
      measured by kappa statistic was found between all percent fibroglandular tissue
      measures (0.72 to 0.63), but only moderate agreement for log fibroglandular
      volumes. The kappa statistics for all percent density measures were highest in
      the comparisons of the SXA and MRI results. The largest error source between MRI
      and the mammography techniques was found to be differences in measures of total
      breast volume. CONCLUSION: Automated volumetric fibroglandular tissue measures
      from screening digital mammograms were in substantial agreement with MRI and if
      associated with breast cancer could be used in clinical practice to enhance risk
      assessment and prevention.

PMID- 24324713
TI  - Icaritin inhibits JAK/STAT3 signaling and growth of renal cell carcinoma.
AB  - Signal transducer and activator of transcription-3 (STAT3) is critical for cancer
      progression by regulating tumor cell survival, proliferation, and angiogenesis.
      Herein, we investigated the regulation of STAT3 activation and the therapeutic
      effects of Icaritin, a prenyl flavonoid derivative from Epimedium Genus, in renal
      cell carcinoma (RCC). Icaritin showed significant anti-tumor activity in the
      human and mouse RCC cell lines, 786-O and Renca, respectively. Icaritin inhibited
      both constitutive and IL-6-induced phospho-STAT3 (STAT3(Y705)) and reduced the
      level of STAT3-regulated proteins Bcl-xL, Mcl-1, Survivin, and CyclinD1 in a dose
      dependent manner. Icaritin also inhibited activation of Janus-activated kinase-2
      (JAK2), while it showed minimal effects on the activation of other key signaling
      pathways, including AKT and MAPK. Expression of the constitutively active form of
      STAT3 blocked Icaritin-induced apoptosis, while siRNA directed against STAT3
      potentiated apoptosis. Finally, Icaritin significantly blunted RCC tumor growth
      in vivo, reduced STAT3 activation, and inhibited Bcl-xL and Cyclin E, as well as
      VEGF expression in tumors, which was associated with reduced tumor angiogenesis.
      Overall, these results suggest that Icaritin strongly inhibits STAT3 activation
      and is a potentially effective therapeutic option for the treatment of renal cell
      carcinoma. 

PMID- 24324715
TI  - Immune response to combination therapy for non-Hodgkin lymphomas.
AB  - A parametric model of tumor response to combination therapy in the presence of an
      immune system is described. Synergistic mechanisms which induce tumor regression
      are simulated with a coupled set of equations. The simulations are first compared
      to tumor history data obtained with a SCID mouse model to determine key
      parameters; predictions are then made for an immune-competent animal. The minimum
      immune cell birth rate relative to malignant B-cell birth rate necessary to
      induce tumor regression is determined, and optimization of drug combinations in
      the presence of an immune response is explored. The delayed effect of an immune
      response relative to drug scheduling is examined, and a mechanism for disease
      transformation in heterogeneous tumors is proposed. 

PMID- 24324716
TI  - The development of the Older Persons and Informal Caregivers Survey Minimum
      DataSet (TOPICS-MDS): a large-scale data sharing initiative.
AB  - INTRODUCTION: In 2008, the Ministry of Health, Welfare and Sport commissioned the
      National Care for the Elderly Programme. While numerous research projects in
      older persons' health care were to be conducted under this national agenda, the
      Programme further advocated the development of The Older Persons and Informal
      Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all
      funded research protocols. In this context, we describe TOPICS data sharing
      initiative (www.topics-mds.eu). MATERIALS AND METHODS: A working group drafted
      TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary
      panel. Using instruments validated for older populations, information was
      collected on demographics, morbidity, quality of life, functional limitations,
      mental health, social functioning and health service utilisation. For informal
      caregivers, information was collected on demographics, hours of informal care and
      quality of life (including subjective care-related burden). RESULTS: Between 2010
      and 2013, a total of 41 research projects contributed data to TOPICS-MDS,
      resulting in preliminary data available for 32,310 older persons and 3,940
      informal caregivers. The majority of studies sampled were from primary care
      settings and inclusion criteria differed across studies. DISCUSSION: TOPICS-MDS
      is a public data repository which contains essential data to better understand
      health challenges experienced by older persons and informal caregivers. Such
      findings are relevant for countries where increasing health-related expenditure
      has necessitated the evaluation of contemporary health care delivery. Although
      open sharing of data can be difficult to achieve in practice, proactively
      addressing issues of data protection, conflicting data analysis requests and
      funding limitations during TOPICS-MDS developmental phase has fostered a data
      sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41
      research projects, thus supporting the feasibility of constructing a large
      (>30,000 observations), standardised dataset pooled from various study protocols
      with different sampling frameworks. This unique implementation strategy improves
      efficiency and facilitates individual-level data meta-analysis.

PMID- 24324714
TI  - Modulation of malaria infection in Anopheles gambiae mosquitoes exposed to
      natural midgut bacteria.
AB  - The development of Plasmodium falciparum within the Anopheles gambiae mosquito
      relies on complex vector-parasite interactions, however the resident midgut
      microbiota also plays an important role in mediating parasite infection. In
      natural conditions, the mosquito microbial flora is diverse, composed of
      commensal and symbiotic bacteria. We report here the isolation of culturable
      midgut bacteria from mosquitoes collected in the field in Cameroon and their
      identification based on the 16S rRNA gene sequencing. We next measured the effect
      of selected natural bacterial isolates on Plasmodium falciparum infection
      prevalence and intensity over multiple infectious feedings and found that the
      bacteria significantly reduced the prevalence and intensity of infection. These
      results contrast with our previous study where the abundance of
      Enterobacteriaceae positively correlated with P. falciparum infection (Boissiere
      et al. 2012). The oral infection of bacteria probably led to the disruption of
      the gut homeostasis and activated immune responses, and this pinpoints the
      importance of studying microbe-parasite interactions in natural conditions. Our
      results indicate that the effect of bacterial exposure on P. falciparum infection
      varies with factors from the parasite and the human host and calls for deeper
      dissection of these parameters for accurate interpretation of bacterial exposure
      results in laboratory settings. 

PMID- 24324717
TI  - Set shifting training with categorization tasks.
AB  - The very few cognitive training studies targeting an important executive
      function, set shifting, have reported performance improvements that also
      generalized to untrained tasks. The present randomized controlled trial extends
      set shifting training research by comparing previously used cued training with
      uncued training. A computerized adaptation of the Wisconsin Card Sorting Test was
      utilized as the training task in a pretest-posttest experimental design involving
      three groups of university students. One group received uncued training (n = 14),
      another received cued training (n = 14) and the control group (n = 14) only
      participated in pre- and posttests. The uncued training group showed posttraining
      performance increases on their training task, but neither training group showed
      statistically significant transfer effects. Nevertheless, comparison of effect
      sizes for transfer effects indicated that our results did not differ
      significantly from the previous studies. Our results suggest that the cognitive
      effects of computerized set shifting training are mostly task-specific, and would
      preclude any robust generalization effects with this training. 

PMID- 24324718
TI  - Strong impact of temporal resolution on the structure of an ecological network.
AB  - Most ecological networks are analysed as static structures, where all observed
      species and links are present simultaneously. However, this is over-simplified,
      because networks are temporally dynamical. We resolved an arctic, entire-season
      plant-flower visitor network into a temporal series of 1-day networks and
      compared the properties with its static equivalent based on data pooled over the
      entire season. Several properties differed. The nested link pattern in the static
      network was blurred in the dynamical version, because the characteristic long
      nestedness tail of flower-visitor specialists got stunted in the dynamical
      networks. This tail comprised a small food web of pollinators, parasitoids and
      hyper-parasitoids. The dynamical network had strong time delays in the
      transmission of direct and indirect effects among species. Twenty percent of all
      indirect links were impossible in the dynamical network. Consequently, properties
      and thus also robustness of ecological networks cannot be deduced from the static
      topology alone. 

PMID- 24324719
TI  - Replicability and heterogeneity of awake unrestrained canine FMRI responses.
AB  - Previously, we demonstrated the possibility of fMRI in two awake and unrestrained
      dogs. Here, we determined the replicability and heterogeneity of these results in
      an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed
      region-of-interest, we compared the caudate response to a hand signal indicating
      the imminent availability of a food reward to a hand signal indicating no reward.
      8 of 13 dogs had a positive differential caudate response to the signal
      indicating reward. The mean differential caudate response was 0.09%, which was
      similar to a comparable human study. These results show that canine fMRI is
      reliable and can be done with minimal stress to the dogs. 

PMID- 24324720
TI  - Fish oil replacement in current aquaculture feed: is cholesterol a hidden
      treasure for fish nutrition?
AB  - Teleost fish, as with all vertebrates, are capable of synthesizing cholesterol
      and as such have no dietary requirement for it. Thus, limited research has
      addressed the potential effects of dietary cholesterol in fish, even if fish meal
      and fish oil are increasingly replaced by vegetable alternatives in modern
      aquafeeds, resulting in progressively reduced dietary cholesterol content. The
      objective of this study was to determine if dietary cholesterol fortification in
      a vegetable oil-based diet can manifest any effects on growth and feed
      utilization performance in the salmonid fish, the rainbow trout. In addition,
      given a series of studies in mammals have shown that dietary cholesterol can
      directly affect the fatty acid metabolism, the apparent in vivo fatty acid
      metabolism of fish fed the experimental diets was assessed. Triplicate groups of
      juvenile fish were fed one of two identical vegetable oil-based diets, with
      additional cholesterol fortification (high cholesterol; H-Chol) or without (low
      cholesterol; L-Chol), for 12 weeks. No effects were observed on growth and feed
      efficiency, however, in fish fed H-Col no biosynthesis of cholesterol, and a
      remarkably decreased apparent in vivo fatty acid beta-oxidation were recorded,
      whilst in L-Chol fed fish, cholesterol was abundantly biosynthesised and an
      increased apparent in vivo fatty acid beta-oxidation was observed. Only minor
      effects were observed on the activity of stearyl-CoA desaturase, but a
      significant increase was observed for both the transcription rate in liver and
      the apparent in vivo activity of the fatty acid Delta-6 desaturase and elongase,
      with increasing dietary cholesterol. This study showed that the possible effects
      of reduced dietary cholesterol in current aquafeeds can be significant and
      warrant future investigations. 

PMID- 24324721
TI  - Transcranial direct current stimulation of the dorsolateral prefrontal cortex
      modulates repetition suppression to unfamiliar faces: an ERP study.
AB  - Repeated visual processing of an unfamiliar face suppresses neural activity in
      face-specific areas of the occipito-temporal cortex. This "repetition
      suppression" (RS) is a primitive mechanism involved in learning of unfamiliar
      faces, which can be detected through amplitude reduction of the N170 event
      related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top
      down influence on early visual processing. However, its contribution to N170 RS
      and learning of unfamiliar faces remains unclear. Transcranial direct current
      stimulation (tDCS) transiently increases or decreases cortical excitability, as a
      function of polarity. We hypothesized that DLPFC excitability modulation by tDCS
      would cause polarity-dependent modulations of N170 RS during encoding of
      unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term
      recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment
      would compromise recognition ability. Participants underwent three tDCS
      conditions in random order at ~72 hour intervals: right anodal/left cathodal,
      right cathodal/left anodal and sham. Immediately following tDCS conditions, an
      EEG was recorded during encoding of unfamiliar faces for assessment of P100 and
      N170 visual ERPs. The P3a component was analyzed to detect prefrontal function
      modulation. Recognition tasks were administered ~72 hours following encoding.
      Results indicate the right anodal/left cathodal condition facilitated N170 RS and
      induced larger P3a amplitudes, leading to faster recognition RT. Conversely, the
      right cathodal/left anodal condition caused N170 amplitude and RTs to increase,
      and a delay in P3a latency. These data demonstrate that DLPFC excitability
      modulation can influence early visual encoding of unfamiliar faces, highlighting
      the importance of DLPFC in basic learning mechanisms. 

PMID- 24324722
TI  - Discovery of an endosymbiotic nitrogen-fixing cyanobacterium UCYN-A in
      Braarudosphaera bigelowii (Prymnesiophyceae).
AB  - Braarudosphaera bigelowii (Prymnesiophyceae) is a coastal coccolithophore with a
      long fossil record, extending back to the late Cretaceous (ca. 100 Ma). A recent
      study revealed close phylogenetic relationships between B. bigelowii,
      Chrysochromulina parkeae (Prymnesiophyceae), and a prymnesiophyte that forms a
      symbiotic association with the nitrogen-fixing cyanobacterium UCYN-A. In order to
      further examine these relationships, we conducted transmission electron
      microscopic and molecular phylogenetic studies of B. bigelowii. TEM studies
      showed that, in addition to organelles, such as the nucleus, chloroplasts and
      mitochondria, B. bigelowii contains one or two spheroid bodies with internal
      lamellae. In the 18S rDNA tree of the Prymnesiophyceae, C. parkeae fell within
      the B. bigelowii clade, and was close to B. bigelowii Genotype III (99.89%
      similarity). Plastid 16S rDNA sequences obtained from B. bigelowii were close to
      the unidentified sequences from the oligotrophic SE Pacific Ocean (e.g. HM133411)
      (99.86% similarity). Bacterial16S rDNA sequences obtained from B. bigelowii were
      identical to the UCYN-A sequence AY621693 from Arabian Sea, and fell in the UCYN
      A clade. From these results, we suggest that; 1) C. parkeae is the alternate life
      cycle stage of B. bigelowii sensu stricto or that of a sibling species of B.
      bigelowii, and 2) the spheroid body of B. bigelowii originated from endosymbiosis
      of the nitrogen-fixing cyanobacterium UCYN-A. 

PMID- 24324723
TI  - Response of demographic rates of tropical trees to light availability: can
      position-based competition indices replace information from canopy census data?
AB  - For trees in tropical forests, competition for light is thought to be a central
      process that offers opportunities for niche differentiation through light
      gradient partitioning. In previous studies, a canopy index based on three
      dimensional canopy census data has been shown to be a good predictor of species
      specific demographic rates across the entire tree community on Barro Colorado
      Island, Panama, and has allowed quantifying between-species variation in light
      response. However, almost all other forest census plots lack data on the canopy
      structure. Hence, this study aims at assessing whether position-based
      neighborhood competition indices can replace information from canopy census data
      and produce similar estimates of the interspecific variation of light responses.
      We used inventory data from the census plot at Barro Colorado Island and
      calculated neighborhood competition indices with varying relative effects of the
      size and distance of neighboring trees. Among these indices, we selected the one
      that was most strongly correlated with the canopy index. We then compared
      outcomes of hierarchical Bayesian models for species-specific recruitment and
      growth rates including either the canopy index or the selected neighborhood
      competition index as predictor. Mean posterior estimates of light response
      parameters were highly correlated between models (r>0.85) and indicated that most
      species regenerate and grow better in higher light. Both light estimation
      approaches consistently found that the interspecific variation of light response
      was larger for recruitment than for growth rates. However, the classification of
      species into different groups of light response, e.g. weaker than linear
      (decelerating) vs. stronger than linear (accelerating) differed between
      approaches. These results imply that while the classification into light response
      groups might be biased when using neighborhood competition indices, they may be
      useful for determining species rankings and between-species variation of light
      response and therefore enable large comparative studies between different forest
      census plots. 

PMID- 24324724
TI  - The effects of intra-abdominal hypertension on the secretory function of canine
      adrenal glands.
AB  - Intra-abdominal hypertension (IAH) can damage multiple organ systems, but the
      explicit impact on the adrenal gland is unclear. To evaluate the effects of intra
      abdominal pressure (IAP) on the secretory function of the adrenal glands, we
      established canine models of IAH. By comparing morphology; hemodynamics; plasma
      cortisol, aldosterone, epinephrine, and norepinephrine concentrations; and the
      expression of IL-1, IL-6, and TNF-alpha in adrenal gland tissue from these dogs,
      we found that hemodynamic instability occurred after IAH and that IAH increased
      the plasma cortisol, aldosterone, epinephrine, and norepinephrine concentrations.
      Higher IAPs resulted in more significant changes, and the above indicators
      gradually returned to normal 2 h after decompression. Compared with the sham
      operated group, IAH significantly increased IL-1, IL-6, and TNF-alpha levels in
      adrenal tissue, with larger increases in the presence of higher IAPs. However,
      the concentrations of these markers remained higher than those in the sham
      operated group despite their decrease after 2 h of decompression.
      Histopathological examination revealed congestion, red blood cell exudation, and
      neutrophil infiltration in the adrenal glands when IAP was elevated; these
      conditions became more significant with more severe IAH. These results suggest
      that the secretion of adrenal hormones and adrenal gland inflammation are
      positively correlated with IAP and that abdominal decompression effectively
      corrects adrenal gland function. 

PMID- 24324725
TI  - Phase III trials of standard chemotherapy with or without bevacizumab for ovarian
      cancer: a meta-analysis.
AB  - BACKGROUND: Platinum-based standard chemotherapy improves survival of ovarian
      cancer (OC), but the five-year survival rate remains below 50%. Antiangiogenic
      agents (7.5 or 15 mg/kg Bevacizumab, Bev) plus to standard chemotherapy improve
      progression-free survival (PFS) not overall survival (OS) in completed randomized
      controlled trials (RCTs). The efficacy and safety of two doses of Bev + standard
      chemotherapy remain controversial. METHODS: MEDLINE, EMBASE, Cochrane Central
      Register of Controlled Trials, Cochrane databases and ClinicalTrials.gov were
      searched. The outcomes of eligible RCTs included PFS, OS and toxicities. Hazard
      ratio (HR) and relative risk (RR) were used for the meta-analysis and were
      expressed with 95% confidence intervals (CIs). RESULTS: Bev + chemotherapy
      improved PFS (HR, 0.82; 95% CI, 0.75 to 0.89; P = .000) and OS (HR, 0.87; 95% CI,
      0.77 to 0.99; P = .026) in newly diagnosed OC (2 trials, 2776 patients), and PFS
      (HR, 0.48; 95% CI, 0.41 to 0.57; P = .000) in recurrent OC (2 trials, 845
      patients). Bev + chemotherapy increased non-CNS bleeding (RR, 3.63; 95% CI, 1.81
      to 7.29; P = .000), hypertension grade >= 2 (RR, 4.90; 95% CI, 3.83 to 6.25; P =
      .000), arterial thromboembolism (RR, 2.29; 95% CI, 1.33 to 3.94; P = .003),
      gastrointestinal perforation (RR, 2.90; 95% CI, 1.44 to 5.82; P = .003), and
      proteinuria grade >= 3 (RR, 6.63; 95% CI 3.17 to 13.88; P = .000). No difference
      was observed between the two Bev doses in PFS (HR, 1.04; 95% CI, 0.88 to 1.24) or
      OS (HR, 1.15, 95% CI, 0.88 to 1.50), but 15 mg/kg Bev increased toxicities.
      CONCLUSION: Bev + standard chemotherapy delayed progression for newly diagnosed
      and recurrent OC, and improved survival for newly diagnosed OC. The 7.5 mg/kg
      dose appeared to be optimal for newly diagnosed OC patients with high risk for
      progression.

PMID- 24324726
TI  - Cell proliferation, movement and differentiation during maintenance of the adult
      mouse adrenal cortex.
AB  - Appropriate maintenance and regeneration of adult endocrine organs is important
      in both normal physiology and disease. We investigated cell proliferation,
      movement and differentiation in the adult mouse adrenal cortex, using different 5
      bromo-2'-deoxyuridine (BrdU) labelling regimens and immunostaining for phenotypic
      steroidogenic cell markers. Pulse-labelling showed that cell division was largely
      confined to the outer cortex, with most cells moving inwards towards the medulla
      at around 13-20 um per day, though a distinct labelled cell population remained
      in the outer 10% of the cortex. Pulse-chase-labelling coupled with phenotypic
      immunostaining showed that, unlike cells in the inner cortex, most BrdU-positive
      outer cortical cells did not express steroidogenic markers, while co-staining for
      BrdU and Ki67 revealed that some outer cortical BrdU-positive cells were induced
      to proliferate following acute adrenocorticotropic hormone (ACTH) treatment.
      Extended pulse-chase-labelling identified cells in the outer cortex which
      retained BrdU label for up to 18-23 weeks. Together, these observations are
      consistent with the location of both slow-cycling stem/progenitor and transiently
      amplifying cell populations in the outer cortex. Understanding the relationships
      between these distinct adrenocortical cell populations will be crucial to clarify
      mechanisms underpinning adrenocortical maintenance and long-term adaptation to
      pathophysiological states. 

PMID- 24324727
TI  - Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise
      in skeletal muscle.
AB  - Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to
      energy provision and is implicated in many metabolic disorders. Exercise training
      increases mitochondrial oxidative capacity in skeletal muscle yet it remains
      unclear if oxidative stress plays a role in regulating these adaptations. We
      demonstrate that the chronic elevation in mitochondrial oxidative stress present
      in Sod2 (+/-) mice impairs the functional and biochemical mitochondrial
      adaptations to exercise. Following exercise training Sod2 (+/-) mice fail to
      increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy
      number, despite a normal augmentation of mitochondrial proteins. Additionally,
      exercised Sod2 (+/-) mice cannot compensate for their higher amount of basal
      mitochondrial oxidative damage and exhibit poor electron transport chain complex
      assembly that accounts for their compromised adaptation. Overall, these results
      demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not
      impact exercise induced mitochondrial biogenesis, but impairs the resulting
      mitochondrial protein function and can limit metabolic plasticity. 

PMID- 24324728
TI  - The prognostic value of mitotic activity index (MAI), phosphohistone H3 (PPH3),
      cyclin B1, cyclin A, and Ki67, alone and in combinations, in node-negative
      premenopausal breast cancer.
AB  - Proliferation, either as the main common denominator in genetic profiles, or in
      the form of single factors such as Ki67, is recommended for clinical use
      especially in estrogen receptor-positive (ER) patients. However, due to high
      costs of genetic profiles and lack of reproducibility for Ki67, studies on other
      proliferation factors are warranted. The aim of the present study was to evaluate
      the prognostic value of the proliferation factors mitotic activity index (MAI),
      phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in
      combinations. In 222 consecutive premenopausal node-negative breast cancer
      patients (87% without adjuvant medical treatment), MAI was assessed on whole
      tissue sections (predefined cut-off >=10 mitoses), and PPH3, cyclin B1, cyclin A,
      and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable
      analysis (high versus low) the strongest prognostic proliferation factor for 10
      year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence
      Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A
      combination variable, with patients with MAI and/or cyclin A high defined as high
      risk, had even stronger prognostic value (HR=4.2, 95%CI: 2.2-7). When stratifying
      for ER-status, MAI was a significant prognostic factor in ER-positive patients
      only (HR=7.0, 95%CI: 3.1-16). Stratified for histological grade, MAI added
      prognostic value in grade 2 (HR=7.2, 95%CI: 3.1-38) and grade 1 patients. In
      multivariable analysis including HER2, age, adjuvant medical treatment, ER, and
      one proliferation factor at a time, only MAI (HR=2.7, 95%CI: 1.1-6.7), and cyclin
      A (HR=2.7, 95%CI: 1.2-6.0) remained independently prognostic. In conclusion this
      study confirms the strong prognostic value of all proliferation factors,
      especially MAI and cyclin A, in all patients, and more specifically in ER
      positive patients, and patients with histological grade 2 and 1. Additionally, by
      combining two proliferation factors, an even stronger prognostic value may be
      found. 

PMID- 24324729
TI  - Impact of helminth diagnostic test performance on estimation of risk factors and
      outcomes in HIV-positive adults.
AB  - BACKGROUND: Traditional methods using microscopy for the detection of helminth
      infections have limited sensitivity. Polymerase chain reaction (PCR) assays
      enhance detection of helminths, particularly low burden infections. However,
      differences in test performance may modify the ability to detect associations
      between helminth infection, risk factors, and sequelae. We compared these
      associations using microscopy and PCR. METHODS: This cross-sectional study was
      nested within a randomized clinical trial conducted at 3 sites in Kenya. We
      performed microscopy and real-time multiplex PCR for the stool detection and
      quantification of Ascaris lumbricoides, Necator americanus, Ancylostoma
      duodenale, Strongyloides stercoralis, and Schistosoma species. We utilized
      regression to evaluate associations between potential risk factors or outcomes
      and infection as detected by either method. RESULTS: Of 153 HIV-positive adults
      surveyed, 55(36.0%) and 20(13.1%) were positive for one or more helminth species
      by PCR and microscopy, respectively (p<0.001). PCR-detected infections were
      associated with farming (Prevalence Ratio 1.57, 95% CI: 1.02, 2.40), communal
      water source (PR 3.80, 95% CI: 1.01, 14.27), and no primary education (PR 1.54,
      95% CI: 1.14, 2.33), whereas microscopy-detected infections were not associated
      with any risk factors under investigation. Microscopy-detected infections were
      associated with significantly lower hematocrit and hemoglobin (means of -3.56%
      and -0.77 g/dl) and a 48% higher risk of anemia (PR 1.48, 95% CI: 1.17, 1.88)
      compared to uninfected. Such associations were absent for PCR-detected infections
      unless infection intensity was considered, Infections diagnosed with either
      method were associated with increased risk of eosinophilia (PCR PR 2.42, 95% CI:
      1.02, 5.76; microscopy PR 2.92, 95% CI: 1.29, 6.60). CONCLUSION: Newer diagnostic
      methods, including PCR, improve the detection of helminth infections. This
      heightened sensitivity may improve the identification of risk factors for
      infection while reducing ability to discriminate infections associated with
      adverse clinical outcomes. Quantitative assays can be used to differentiate
      infection loads and discriminate infections associated with sequelae.

PMID- 24324730
TI  - N-glycoproteome analysis of the secretome of human metastatic hepatocellular
      carcinoma cell lines combining hydrazide chemistry, HILIC enrichment and mass
      spectrometry.
AB  - Cancer cell metastasis is a major cause of cancer death. Unfortunately, the
      underlying molecular mechanisms remain unknown, which results in the lack of
      efficient diagnosis, therapy and prevention approaches. Nevertheless, the
      dysregulation of the cancer cell secretome is known to play key roles in tumor
      transformation and progression. The majority of proteins in the secretome are
      secretory proteins and membrane-released proteins, and, mostly, the glycosylated
      proteins. Until recently, few studies have explored protein N-glycosylation
      changes in the secretome, although protein glycosylation has received increasing
      attention in the study of tumor development processes. Here, the N-glycoproteins
      in the secretome of two human hepatocellular carcinoma (HCC) cell lines with low
      (MHCC97L) or high (HCCLM3) metastatic potential were investigated with a in-depth
      characterization of the N-glycosites by combining two general glycopeptide
      enrichment approaches, hydrazide chemistry and zwitterionic hydrophilic
      interaction chromatography (zic-HILIC), with mass spectrometry analysis. A total
      of 1,213 unique N-glycosites from 611 N-glycoproteins were confidently
      identified. These N-glycoproteins were primarily localized to the extracellular
      space and plasma membrane, supporting the important role of N-glycosylation in
      the secretory pathway. Coupling label-free quantification with a hierarchical
      clustering strategy, we determined the differential regulation of several N
      glycoproteins that are related to metastasis, among which AFP, DKK1, FN1, CD151
      and TGFbeta2 were up-regulated in HCCLM3 cells. The inclusion of the well-known
      metastasis-related proteins AFP and DKK1 in this list provides solid supports for
      our study. Further western blotting experiments detecting FN1 and FAT1 confirmed
      our discovery. The glycoproteome strategy in this study provides an effective
      means to explore potential cancer biomarkers. 

PMID- 24324731
TI  - Analysis of the overall structure of the multi-domain amyloid precursor protein
      (APP).
AB  - The amyloid precursor protein (APP) and its processing by the alpha-, beta- and
      gamma-secretases is widely believed to play a central role during the development
      of Alzheimer's disease. The three-dimensional structure of the entire protein,
      its physiologic function and the regulation of its proteolytic processing remain,
      however, largely unclear to date. To gain a deeper understanding of the structure
      of APP that underlies all of its functions, we first cloned and recombinantly
      expressed different constructs in E. coli. Using limited proteolysis followed by
      mass spectrometry and Edman degradation as well as analytical gel permeation
      chromatography coupled static light scattering, we experimentally analyzed the
      structural domain boundaries and determined that the large ectodomain of APP
      consists of exactly two rigidly folded domains - the E1-domain (Leu18-Ala190) and
      the E2-domain (Ser295-Asp500). Both, the acidic domain (AcD) connecting E1 and E2
      as well as the juxtamembrane region (JMR) connecting E2 to the single
      transmembrane helix are highly flexible and extended. We identified in-between
      the E1-domain and the AcD an additional domain of conservation and partial
      flexibility that we termed extension domain (ED, Glu191-Glu227). Using Bio-layer
      interferometry, pull-down assays and analytical gel filtration experiments we
      demonstrated that the E1-domain does not tightly interact with the E2-domain,
      both in the presence and in the absence of heparin. APP hence forms an extended
      molecule that is flexibly tethered to the membrane. Its multi-domain architecture
      enables together with the many known functionalities the concomitant performance
      of several, independent functions, which might be regulated by cellular,
      compartment specific pH-changes. 

PMID- 24324732
TI  - Up-regulation of adiponectin expression in antigravitational soleus muscle in
      response to unloading followed by reloading, and functional overloading in mice.
AB  - The purpose of this study was to investigate the expression level of adiponectin
      and its related molecules in hypertrophied and atrophied skeletal muscle in mice.
      The expression was also evaluated in C2C12 myoblasts and myotubes. Both mRNA and
      protein expression of adiponectin, mRNA expression of adiponectin receptor
      (AdipoR) 1 and AdipoR2, and protein expression of adaptor protein containing
      pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper
      motif 1 (APPL1) were observed in C2C12 myoblasts. The expression levels of these
      molecules in myotubes were higher than those in myoblasts. The expression of
      adiponectin-related molecules in soleus muscle was observed at mRNA (adiponectin,
      AdipoR1, AdipoR2) and protein (adiponectin, APPL1) levels. The protein expression
      levels of adiponectin and APPL1 were up-regulated by 3 weeks of functional
      overloading. Down-regulation of AdipoR1 mRNA, but not AdipoR2 mRNA, was observed
      in atrophied soleus muscle. The expression of adiponectin protein, AdipoR1 mRNA,
      and APPL1 protein was up-regulated during regrowth of unloading-associated
      atrophied soleus muscle. Mechanical loading, which could increase skeletal muscle
      mass, might be a useful stimulus for the up-regulations of adiponectin and its
      related molecules in skeletal muscle. 

PMID- 24324733
TI  - Predicting the activity coefficients of free-solvent for concentrated globular
      protein solutions using independently determined physical parameters.
AB  - The activity coefficient is largely considered an empirical parameter that was
      traditionally introduced to correct the non-ideality observed in thermodynamic
      systems such as osmotic pressure. Here, the activity coefficient of free-solvent
      is related to physically realistic parameters and a mathematical expression is
      developed to directly predict the activity coefficients of free-solvent, for
      aqueous protein solutions up to near-saturation concentrations. The model is
      based on the free-solvent model, which has previously been shown to provide
      excellent prediction of the osmotic pressure of concentrated and crowded globular
      proteins in aqueous solutions up to near-saturation concentrations. Thus, this
      model uses only the independently determined, physically realizable quantities:
      mole fraction, solvent accessible surface area, and ion binding, in its
      prediction. Predictions are presented for the activity coefficients of free
      solvent for near-saturated protein solutions containing either bovine serum
      albumin or hemoglobin. As a verification step, the predictability of the model
      for the activity coefficient of sucrose solutions was evaluated. The predicted
      activity coefficients of free-solvent are compared to the calculated activity
      coefficients of free-solvent based on osmotic pressure data. It is observed that
      the predicted activity coefficients are increasingly dependent on the solute
      solvent parameters as the protein concentration increases to near-saturation
      concentrations. 

PMID- 24324734
TI  - Early IFN-gamma production after YF 17D vaccine virus immunization in mice and
      its association with adaptive immune responses.
AB  - Yellow Fever vaccine is one of the most efficacious human vaccines ever made. The
      vaccine (YF 17D) virus induces polyvalent immune responses, with a mixed TH1/TH2
      CD4(+) cell profile, which results in robust T CD8(+) responses and high titers
      of neutralizing antibody. In recent years, it has been suggested that early
      events after yellow fever vaccination are crucial to the development of adequate
      acquired immunity. We have previously shown that primary immunization of humans
      and monkeys with YF 17D virus vaccine resulted in the early synthesis of IFN
      gamma. Herein we have demonstrated, for the first time that early IFN-gamma
      production after yellow fever vaccination is a feature also of murine infection
      and is much more pronounced in the C57BL/6 strain compared to the BALB/c strain.
      Likewise, in C57BL/6 strain, we have observed the highest CD8(+) T cells
      responses as well as higher titers of neutralizing antibodies and total anti-YF
      IgG. Regardless of this intense IFN-gamma response in mice, it was not possible
      to see higher titers of IgG2a in relation to IgG1 in both mice lineages. However,
      IgG2a titers were positively correlated to neutralizing antibodies levels,
      pointing to an important role of IFN-gamma in eliciting high quality responses
      against YF 17D, therefore influencing the immunogenicity of this vaccine. 

PMID- 24324735
TI  - Oct4/Sox2 binding sites contribute to maintaining hypomethylation of the maternal
      igf2/h19 imprinting control region.
AB  - A central question in genomic imprinting is how parental-specific DNA methylation
      of imprinting control regions (ICR) is established during gametogenesis and
      maintained after fertilization. At the imprinted Igf2/H19 locus, CTCF binding
      maintains the unmethylated state of the maternal ICR after the blastocyst stage.
      In addition, evidence from Beckwith-Wiedemann patients and cultured mouse cells
      suggests that two Sox-Oct binding motifs within the Igf2/H19 ICR also participate
      in maintaining hypomethylation of the maternal allele. We found that the Sox and
      octamer elements from both Sox-Oct motifs were required to drive hypomethylation
      of integrated transgenes in mouse embryonic carcinoma cells. Oct4 and Sox2 showed
      cooperative binding to the Sox-Oct motifs, and both were present at the
      endogenous ICR. Using a mouse with mutations in the Oct4 binding sites, we found
      that maternally transmitted mutant ICRs acquired partial methylation in somatic
      tissues, but there was little effect on imprinted expression of H19 and Igf2. A
      subset of mature oocytes also showed partial methylation of the mutant ICR, which
      suggested that the Sox-Oct motifs provide some protection from methylation during
      oogenesis. The Sox-Oct motifs, however, were not required for erasure of paternal
      methylation in primordial germ cells, which indicated that the oocyte methylation
      was acquired post-natally. Maternally inherited mutant ICRs were unmethylated in
      blastocysts, which suggested that at least a portion of the methylation in
      somatic tissues occurred after implantation. These findings provide evidence that
      Sox-Oct motifs contribute to ICR hypomethylation in post-implantation embryos and
      maturing oocytes and link imprinted DNA methylation with key stem cell/germline
      transcription factors. 

PMID- 24324736
TI  - An immunomodulating fatty acid analogue targeting mitochondria exerts anti
      atherosclerotic effect beyond plasma cholesterol-lowering activity in apoe(-/-)
      mice.
AB  - Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with
      immunomodulating properties involving activation of peroxisome proliferator
      activated receptors (PPARs) and proliferation of mitochondria. This study aimed
      to penetrate the effect of TTA on the development of atherosclerotic lesions in
      apolipoprotein (apo)-E(-/-) mice fed a high-fat diet containing 0.3% TTA for 12
      weeks. These mice displayed a significantly less atherosclerotic development vs
      control. Plasma cholesterol was increased by TTA administration and
      triacylglycerol (TAG) levels in plasma and liver were decreased by TTA
      supplementation, the latter, probably due to increased mitochondrial fatty acid
      oxidation and reduced lipogenesis. TTA administration also changed the fatty acid
      composition in the heart, and the amount of arachidonic acid (ARA) and
      eicosapentaenoic acid (EPA) was reduced and increased, respectively. The heart
      mRNA expression of inducible nitric oxidase (NOS)-2 was decreased in TTA-treated
      mice, whereas the mRNA level of catalase was increased. Finally, reduced plasma
      levels of inflammatory mediators as IL-1alpha, IL-6, IL-17, TNF-alpha and IFN
      gamma were detected in TTA-treated mice. These data show that TTA reduces
      atherosclerosis in apoE(-/-) mice and modulates risk factors related to
      atherosclerotic disorders. TTA probably acts at both systemic and vascular levels
      in a manner independent of changes in plasma cholesterol, and triggers TAG
      catabolism through improved mitochondrial function. 

PMID- 24324737
TI  - The resveratrol tetramer (-)-hopeaphenol inhibits type III secretion in the gram
      negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa.
AB  - Society faces huge challenges, as a large number of bacteria have developed
      resistance towards many or all of the antibiotics currently available. Novel
      strategies that can help solve this problem are urgently needed. One such
      strategy is to target bacterial virulence, the ability to cause disease e.g., by
      inhibition of type III secretion systems (T3SSs) utilized by many clinically
      relevant gram-negative pathogens. Many of the antibiotics used today originate
      from natural sources. In contrast, most virulence-blocking compounds towards the
      T3SS identified so far are small organic molecules. A recent high-throughput
      screening of a prefractionated natural product library identified the resveratrol
      tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia
      pseudotuberculosis. In this study we have investigated the virulence blocking
      properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)
      Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia
      pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In
      addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth
      of Chlamydia trachomatis. 

PMID- 24324738
TI  - Association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and
      prognosis of esophageal squamous cell carcinoma.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) and nuclear factor of kappa
      light chain gene enhancer in activated B cells (NF-kappaB) play critical role in
      carcinogenesis processes like tumour initiation, proliferation, migration and
      invasion. Single nucleotide polymorphisms in TNF-alpha, NF-kappaB and its
      inhibitor IkappaB genes were shown to be associated with susceptibility and
      prognosis of several cancers; however, their role in esophageal squamous cell
      carcinoma (ESCC) is not well recognised. Therefore, in present study, we aimed to
      investigate association of common polymorphisms in TNFA, NFkB1 and NFKBIA with
      risk and prognosis of ESCC in northern Indian population. METHODS: We genotyped
      290 ESCC patients (including 162 followed up cases) and 311 mean age, gender and
      ethnicity matched controls for TNFA -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (
      826C>T and 3'UTRA>G) polymorphisms using PCR alone or followed by RFLP and TaqMan
      assay. RESULTS: TNFA-308GA genotype was associated with increased risk of ESCC
      specifically in females and in patients with regional lymph node involvement,
      while, NFKBIA -826CT+TT genotype conferred decreased risk of ESCC in females.
      Haplotypes of NFKBIA -826C>T and 3'UTRA>G polymorphisms, C-826G3'UTR and T
      826A3'UTR, were associated with reduced risk of ESCC. No independent role of
      NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi
      dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826,
      NFKBIA 3'UTR as better predictor for risk of ESCC. Furthermore, combined risk
      genotype analysis of all studied polymorphisms showed increased risk of ESCC in
      patients with 1-3 risk genotype compared to '0' risk genotype. Survival analysis
      did not show any significant prognostic effect of studied polymorphisms. However,
      in stepwise multivariate analysis, metastasis was found to be independent
      prognostic predictor of ESCC patients. CONCLUSION: TNFA-308 and NFKBIA (-826C>T
      and 3'UTRA>G) polymorphisms may play role in susceptibility but not in prognosis
      of ESCC patients in northern Indian population.

PMID- 24324739
TI  - Added value of HER-2 amplification testing by multiplex ligation-dependent probe
      amplification in invasive breast cancer.
AB  - BACKGROUND: HER-2 is a prognostic and predictive marker, but as yet no technique
      is perfectly able to identify patients likely to benefit from HER-2 targeted
      therapies. We aimed to prospectively assess the added value of first-line co
      testing by IHC, and multiplex ligation-dependent probe amplification (MLPA) and
      chromogenic in situ hybridization (CISH). METHODS: As local validation, HER-2
      MLPA and CISH were compared in 99 breast cancers. Next, we reviewed 937 invasive
      breast cancers, from 4 Dutch pathology laboratories, that were prospectively
      assessed for HER-2 by IHC and MLPA (and CISH in selected cases). RESULTS: The
      validation study demonstrated 100% concordance between CISH and MLPA, if both
      methods were assessable and conclusive (81.8% of cases). Significant variation
      regarding percentages IHC 0/1+ and 2+ cases was observed between the laboratories
      (p<0.0001). Overall concordance between IHC and MLPA/CISH was 98.1% (575/586)
      (Kappa = 0.94). Of the IHC 3+ cases, 6.7% failed to reveal gene amplification,
      whereas 0.8% of the IHC 0/1+ cases demonstrated gene amplification. Results
      remained discordant after retrospective review in 3/11 discordant cases. In the
      remaining 8 cases the original IHC score was incorrect or adapted after repeated
      IHC staining. CONCLUSIONS: MLPA is a low-cost and quantitative high-throughput
      technique with near perfect concordance with CISH. The use of MLPA in routinely
      co-testing all breast cancers may reduce HER-2 testing variation between
      laboratories, may serve as quality control for IHC, will reveal IHC 0/1+ patients
      with gene amplification, likely responsive to trastuzumab, and identify IHC 3+
      cases without gene amplification that may respond less well.

PMID- 24324740
TI  - Characterization of L1 ORF1p self-interaction and cellular localization using a
      mammalian two-hybrid system.
AB  - Long INterspersed Element-1 (LINE-1, L1) is an active retrotransposon that
      mobilizes using a ribonucleoprotein particle (RNP) intermediate composed of the
      full-length bicistronic L1 mRNA and the two proteins (ORF1p and ORF2p) encoded by
      that mRNA. ORF1p and ORF2p demonstrate cis-preference for their encoding mRNA.
      Previous studies of ORF1p, purified from bacterial and insect cells demonstrated
      that this protein forms trimers in vitro. While valuable for understanding ORF1p
      function, these in vitro approaches do not provide any information on ORF1p self
      interaction in the context of mammalian cells. We used a mammalian two-hybrid
      (M2H) system in order to study L1 ORF1p self-interaction in human and mouse
      cells. We demonstrate that the M2H system successfully detects human and mouse
      ORF1p self-interactions in transiently transfected mammalian cells. We also
      generated mouse and human ORF1p-specific antibodies to characterize the
      expression of ORF1p fusion proteins used in the M2H system. Using these
      antibodies, we demonstrate that ORF1p interaction in trans leads to the formation
      of heterodimers that are expected to produce a positive signal in the M2H system.
      Although the role for L1 ORF1p cis-preference in L1 mobilization is established,
      the impact of ability of ORF1pto interact in trans on the L1 replication cycle is
      not known. Furthermore, western blot analysis of ORF1p generated by a full-length
      L1, wild type ORF1, or a codon-optimized ORF1 expression vector is detected in
      the nucleus. In contrast, the addition of a tag to the N-terminus of the mouse
      and human ORF1 proteins can significantly alter the subcellular localization in a
      tag-specific manner. These data support that nuclear localization of ORF1p may
      contribute to L1 (and potentially the SINE Alu) RNP nuclear access in the host
      cell. 

PMID- 24324741
TI  - Comorbidities in children and adolescents with AIDS acquired by HIV vertical
      transmission in Vitoria, Brazil.
AB  - BACKGROUND: Studying diseases associated with AIDS is essential for establishing
      intervention strategies because comorbidities can lead to death. The objectives
      were to describe the frequency of comorbidities and verify their distribution
      according to demographic, epidemiological and clinical data as well as to
      classify diseases in children and adolescents with AIDS in Vitoria, Brazil.
      METHODS: A retrospective cohort study was conducted among children with AIDS, as
      defined according to the criteria established by the Ministry of Health, who
      acquired HIV via vertical transmission, were aged 0 to 18 years, and were
      monitored at a referral hospital from January 2001 to December 2011. RESULTS: A
      total of 177 patients were included, of whom 97 were female (55%). There were 60
      patients (34%) <1 year old, 67 patients (38%) between the ages of 1 and 5, and 50
      patients (28%) >=6 years of age included at the time of admission to the
      Infectious Diseases Ward. Regarding clinical-immunological classification, 146
      patients (82.5%) showed moderate/severe forms of the disease at the time of
      admission into the Ward, and 26 patients (14.7%) died during the study. The most
      common clinical signs were hepatomegaly (81.62%), splenomegaly (63.8%),
      lymphadenopathy (68.4%) and persistent fever (32.8%). The most common
      comorbidities were anaemia (67.2%), pneumonia/septicaemia/acute bacterial
      meningitis (ABM) (64.2%), acute otitis media (AOM)/recurrent sinusitis (55.4%),
      recurrent severe bacterial infections (47.4%) and dermatitis (43.1%). An
      association between severe clinical-immunological classification and admission to
      the Ward for children aged less than one year old was found for several
      comorbidities (p<0.001). CONCLUSION: Delayed diagnosis was observed because the
      majority of patients were admitted to the Infectious Diseases Ward at >=1 year of
      age and were already presenting with serious diseases. The general paediatrician
      should be alert to this possibility to make an early diagnosis in children
      infected with HIV.

PMID- 24324742
TI  - The Pseudomonas syringae pv. tomato type III effector HopM1 suppresses
      Arabidopsis defenses independent of suppressing salicylic acid signaling and of
      targeting AtMIN7.
AB  - Pseudomonas syringae pv tomato strain DC3000 (Pto) delivers several effector
      proteins promoting virulence, including HopM1, into plant cells via type III
      secretion. HopM1 contributes to full virulence of Pto by inducing degradation of
      Arabidopsis proteins, including AtMIN7, an ADP ribosylation factor-guanine
      nucleotide exchange factor. Pseudomonas syringae pv phaseolicola strain NPS3121
      (Pph) lacks a functional HopM1 and elicits robust defenses in Arabidopsis
      thaliana, including accumulation of pathogenesis related 1 (PR-1) protein and
      deposition of callose-containing cell wall fortifications. We have examined the
      effects of heterologously expressed HopM1Pto on Pph-induced defenses. HopM1
      suppresses Pph-induced PR-1 expression, a widely used marker for salicylic acid
      (SA) signaling and systemic acquired resistance. Surprisingly, HopM1 reduces PR-1
      expression without affecting SA accumulation and also suppresses the low levels
      of PR-1 expression apparent in SA-signaling deficient plants. Further, HopM1
      enhances the growth of Pto in SA-signaling deficient plants. AtMIN7 contributes
      to Pph-induced PR-1 expression. However, HopM1 fails to degrade AtMIN7 during Pph
      infection and suppresses Pph-induced PR-1 expression and callose deposition in
      wild-type and atmin7 plants. We also show that the HopM1-mediated suppression of
      PR-1 expression is not observed in plants lacking the TGA transcription factor,
      TGA3. Our data indicate that HopM1 promotes bacterial virulence independent of
      suppressing SA-signaling and links TGA3, AtMIN7, and other HopM1 targets to
      pathways distinct from the canonical SA-signaling pathway contributing to PR-1
      expression and callose deposition. Thus, efforts to understand this key effector
      must consider multiple targets and unexpected outputs of its action. 

PMID- 24324743
TI  - Slow oscillation amplitudes and up-state lengths relate to memory improvement.
AB  - There is growing evidence of the active involvement of sleep in memory
      consolidation. Besides hippocampal sharp wave-ripple complexes and sleep
      spindles, slow oscillations appear to play a key role in the process of sleep
      associated memory consolidation. Furthermore, slow oscillation amplitude and
      spectral power increase during the night after learning declarative and
      procedural memory tasks. However, it is unresolved whether learning-induced
      changes specifically alter characteristics of individual slow oscillations, such
      as the slow oscillation up-state length and amplitude, which are believed to be
      important for neuronal replay. 24 subjects (12 men) aged between 20 and 30 years
      participated in a randomized, within-subject, multicenter study. Subjects slept
      on three occasions for a whole night in the sleep laboratory with full
      polysomnography. Whereas the first night only served for adaptation purposes, the
      two remaining nights were preceded by a declarative word-pair task or by a non
      learning control task. Slow oscillations were detected in non-rapid eye movement
      sleep over electrode Fz. Results indicate positive correlations between the
      length of the up-state as well as the amplitude of both slow oscillation phases
      and changes in memory performance from pre to post sleep. We speculate that the
      prolonged slow oscillation up-state length might extend the timeframe for the
      transfer of initial hippocampal to long-term cortical memory representations,
      whereas the increase in slow oscillation amplitudes possibly reflects changes in
      the net synaptic strength of cortical networks. 

PMID- 24324744
TI  - The Sec63p J-domain is required for ERAD of soluble proteins in yeast.
AB  - How misfolded proteins are exported from the ER to the cytosol for degradation
      (ER-associated Degradation, ERAD) and which proteins are participating in this
      process is not understood. Several studies using a single, leaky mutant indicated
      that Sec63p might be involved in ERAD. More recently, Sec63p was also found
      strongly associated with proteasomes attached to the protein-conducting channel
      in the ER membrane which presumably form part of the export machinery. These
      observations prompted us to reinvestigate the role of Sec63p in ERAD by
      generating new mutants which were selected in a screen monitoring the
      intracellular accumulation of the ERAD substrate CPY*. We show that a mutation in
      the DnaJ-domain of Sec63p causes a defect in ERAD, whereas mutations in the Brl,
      acidic, and transmembrane domains only affect protein import into the ER.
      Unexpectedly, mutations in the acidic domain which mediates interaction of Sec63p
      with Sec62p also caused defects in cotranslational import. In contrast to
      mammalian cells where SEC63 expression levels affect steady-state levels of multi
      spanning transmembrane proteins, the sec63 J-domain mutant was only defective in
      ERAD of soluble substrates. 

PMID- 24324745
TI  - Deletions in cox2 mRNA result in loss of splicing and RNA editing and gain of
      novel RNA editing sites.
AB  - As previously demonstrated, the maize cox2 RNA is fully edited in cauliflower
      mitochondria. Use of constructs with a deleted cox2 intron, however, led to a
      loss of RNA editing at almost all editing sites, with only a few sites still
      partially edited. Likewise, one deletion in exon 1 and three in exon 2 abolish
      RNA editing at all cox2 sites analyzed. Furthermore, intron splicing is abolished
      using these deletions. Mutation of a cytosine residue, which is normally edited
      and localized directly adjacent to the intron, to thymidine did not result in
      restoration of splicing, indicating that the loss of splicing was not due to loss
      of RNA editing. One deletion in exon 2 did not lead to loss of splicing. Instead,
      most editing sites were found to be edited, only three were not edited.
      Unexpectedly, we observed additional RNA editing events at new sites. Thus it
      appears that deletions in the cox2 RNA sequence can have a strong effect on RNA
      processing, leading to loss of splicing, loss of editing at all sites, or even to
      a gain of new editing sites. As these effects are not limited to the vicinity of
      the respective deletions, but appear to be widespread or even affect all editing
      sites, they may not be explained by the loss of PPR binding sites. Instead, it
      appears that several parts of the cox2 transcript are required for proper RNA
      processing. This indicates the roles of the RNA sequence and structural elements
      in the recognition of the editing sites. 

PMID- 24324746
TI  - Orangutans (Pongo pygmaeus) remember old acquaintances.
AB  - Many social animals can discriminate between familiar and unfamiliar faces.
      Orangutans, however, lead a semi-solitary life and spend much of the day alone.
      As such, they may be less adept at recognizing conspecifics and are a good model
      for determining how social structure influences the evolution of social cognition
      such as facial recognition. The present study is the first report of whether
      orangutans can distinguish among individual faces. We adopted a preferential
      looking method and found that orangutans used facial discrimination to identify
      known conspecifics. This suggests that frequent and intense social interaction is
      not necessary for facial discrimination, although our findings were limited by
      the small number of stimuli and the unequal numbers of male and female orangutans
      depicted in the stimuli. 

PMID- 24324747
TI  - Seasonal variation in the spatial distribution of basking sharks (Cetorhinus
      maximus) in the lower Bay of Fundy, Canada.
AB  - The local distribution of basking sharks in the Bay of Fundy (BoF) is unknown
      despite frequent occurrences in the area from May to November. Defining this
      species' spatial habitat use is critical for accurately assessing its Special
      Concern conservation status in Atlantic Canada. We developed maximum entropy
      distribution models for the lower BoF and the northeast Gulf of Maine (GoM) to
      describe spatiotemporal variation in habitat use of basking sharks. Under the
      Maxent framework, we assessed model responses and distribution shifts in relation
      to known migratory behavior and local prey dynamics. We used 10 years (2002-2011)
      of basking shark surface sightings from July-October acquired during boat-based
      surveys in relation to chlorophyll-a concentration, sea surface temperature,
      bathymetric features, and distance to seafloor contours to assess habitat
      suitability. Maximum entropy estimations were selected based on AICc criterion
      and used to predict habitat utilizing three model-fitting routines as well as
      converted to binary suitable/non-suitable habitat using the maximum sensitivity
      and specificity threshold. All models predicted habitat better than random (AUC
      values >0.796). From July-September, a majority of habitat was in the BoF, in
      waters >100 m deep, and in the Grand Manan Basin. In October, a majority of the
      habitat shifted southward into the GoM and to areas >200 m deep. Model responses
      suggest that suitable habitat from July - October is dependent on a mix of
      distance to the 0, 100, 150, and 200 m contours but in some models on sea surface
      temperature (July) and chlorophyll-a (August and September). Our results reveal
      temporally dynamic habitat use of basking sharks within the BoF and GoM. The
      relative importance of predictor variables suggests that prey dynamics
      constrained the species distribution in the BoF. Also, suitable habitat shifted
      minimally from July-September providing opportunities to conserve the species
      during peak abundance in the region. 

PMID- 24324748
TI  - Initial cell seeding density influences pancreatic endocrine development during
      in vitro differentiation of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) have the ability to form cells derived from
      all three germ layers, and as such have received significant attention as a
      possible source for insulin-secreting pancreatic beta-cells for diabetes
      treatment. While considerable advances have been made in generating hESC-derived
      insulin-producing cells, to date in vitro-derived glucose-responsive beta-cells
      have remained an elusive goal. With the objective of increasing the in vitro
      formation of pancreatic endocrine cells, we examined the effect of varying
      initial cell seeding density from 1.3 x 10(4) cells/cm(2) to 5.3 x 10(4)
      cells/cm(2) followed by a 21-day pancreatic endocrine differentiation protocol.
      Low density-seeded cells were found to be biased toward the G2/M phases of the
      cell cycle and failed to efficiently differentiate into SOX17-CXCR4 co-positive
      definitive endoderm cells leaving increased numbers of OCT4 positive cells in day
      4 cultures. Moderate density cultures effectively formed definitive endoderm and
      progressed to express PDX1 in approximately 20% of the culture. High density
      cultures contained approximately double the numbers of PDX1 positive pancreatic
      progenitor cells and also showed increased expression of MNX1, PTF1a, NGN3, ARX,
      and PAX4 compared to cultures seeded at moderate density. The cultures seeded at
      high density displayed increased formation of polyhormonal pancreatic endocrine
      cell populations co-expressing insulin, glucagon and somatostatin. The maturation
      process giving rise to these endocrine cell populations followed the expected
      cascade of pancreatic progenitor marker (PDX1 and MNX1) expression, followed by
      pancreatic endocrine specification marker expression (BRN4, PAX4, ARX, NEUROD1,
      NKX6.1 and NKX2.2) and then pancreatic hormone expression (insulin, glucagon and
      somatostatin). Taken together these data suggest that initial cell seeding
      density plays an important role in both germ layer specification and pancreatic
      progenitor commitment, which precedes pancreatic endocrine cell formation. This
      work highlights the need to examine standard culture variables such as seeding
      density when optimizing hESC differentiation protocols. 

PMID- 24324749
TI  - Cytokeratin 18, alanine aminotransferase, platelets and triglycerides predict the
      presence of nonalcoholic steatohepatitis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the critical
      public health problems in China. The full spectrum of the disease ranges from
      simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and
      hepatocellular carcinoma(HCC). The infiltration of inflammatory cells
      characterizes NASH. This characteristic contributes to the progression of
      hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from
      NAFLD is crucial. OBJECTIVE AND METHODS: Ninety-five patients with NAFLD, 44 with
      NASH, and 51 with non-NASH were included in the study to develop a new scoring
      system for differentiating NASH from NAFLD. Data on clinical and biological
      characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK
      18) fragments levels were measured using an enzyme-linked immunosorbant assay.
      RESULTS: Several indexes show significant differences between the two groups,
      which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
      (ALP), gamma-glutamyl transpeptidase (gamma-GT), platelets, uric acid (UA), hs-C
      reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments
      (all P < 0.05). The CK-18 fragment levels showed a significant positive
      correlation with steatosis severity, ballooning, lobular inflammation, and
      fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT,
      platelets, CK-18 fragments, and TG was established by logistic regression among
      NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 -
      0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive
      predictive value = 89%, negative predictive value = 89%). CONCLUSION: The novel
      scoring system may be considered as a useful model in predicting the presence of
      NASH in NAFLD patients.

PMID- 24324750
TI  - Age of first breeding interacts with pre- and post-recruitment experience in
      shaping breeding phenology in a long-lived gull.
AB  - Individual variation in timing of breeding is a key factor affecting adaptation
      to environmental change, yet our basic understanding of the causes of such
      individual variation is incomplete. This study tests several hypotheses for age
      related variation in the breeding timing of Lesser Black-backed Gulls, based on a
      13 year longitudinal data set that allows to decouple effects of age, previous
      prospecting behavior, and years of breeding experience on arrival timing at the
      colony. At the population level, age of first breeding was significantly
      associated with timing of arrival and survival, i.e. individuals tended to arrive
      later if they postponed their recruitment, and individuals recruiting at the age
      of 4 years survived best. However, up to 81% of the temporal variation in arrival
      dates was explained by within-individual effects. When excluding the pre
      recruitment period, the effect of increasing age on advanced arrival was
      estimated at 11 days, with prior breeding experience accounting for a 7 days
      advance and postponed breeding for a 4 days delay. Overall, results of this study
      show that delayed age of first breeding can serve to advance arrival date (days
      after December 1(st)) in successive breeding seasons throughout an individual's
      lifetime, in large part due to the benefits of learning or experience gained
      during prospecting. However, prospecting and the associated delay in breeding
      also bear a survival cost, possibly because prospectors have been forced to delay
      through competition with breeders. More generally, results of this study set the
      stage for exploring integrated temporal shifts in phenology, resource allocation
      and reproductive strategies during individual lifecycles of long-lived migratory
      species. 

PMID- 24324751
TI  - Alternative activation of macrophages and induction of arginase are not
      components of pathogenesis mediated by Francisella species.
AB  - Virulent Francisella tularensis ssp tularensis is an intracellular, Gram negative
      bacterium that causes acute lethal disease following inhalation of fewer than 15
      organisms. Pathogenicity of Francisella infections is tied to its unique ability
      to evade and suppress inflammatory responses in host cells. It has been proposed
      that induction of alternative activation of infected macrophages is a mechanism
      by which attenuated Francisella species modulate host responses. In this report
      we reveal that neither attenuated F. tularensis Live Vaccine Strain (LVS) nor
      virulent F. tularensis strain SchuS4 induce alternative activation of macrophages
      in vitro or in vivo. LVS, but not SchuS4, provoked production of arginase1
      independent of alternative activation in vitro and in vivo. However, absence of
      arginase1 did not significantly impact intracellular replication of LVS or
      SchuS4. Together our data establish that neither induction of alternative
      activation nor expression of arginase1 are critical features of disease mediated
      by attenuated or virulent Francisella species. 

PMID- 24324752
TI  - Bone mineral density of the spine in 11,898 Chinese infants and young children: a
      cross-sectional study.
AB  - BACKGROUND: Bone mineral density (BMD) increases progressively during childhood
      and adolescence and is affected by various genetic and environmental factors. The
      aim of this study was to establish reference values for lumbar BMD in healthy
      Chinese infants and young children and investigate its influencing factors.
      METHODS AND FINDINGS: Healthy children aged 0 to 3 years who underwent regular
      physical examinations at the Child Health Care Clinic of Hubei Maternal and Child
      Health Hospital (N = 11,898) were recruited for this study. We also chose 379
      preterm infants aged 0 to 1 years to preliminarily explore the development of BMD
      in this special population. BMD (g/cm(2)) measurements of the lumbar spine (L2
      L4) were carried out with dual-energy X-ray absorptiometry and a questionnaire
      was administered to full-term children's parents to gather information on various
      nutritional and lifestyle factors as well as mothers' nutritional supplement use
      during pregnancy. Lumbar BMD significantly increased with age among both boys and
      girls (p<0.05), with fastest growth observed during the first postnatal year.
      There was no significant difference in lumbar BMD between boys and girls of
      similar age (p>0.05), either among healthy reference children or preterm infants.
      However, BMD values in preterm infants were significantly lower than those in
      term infants 3 to 8 months old (p<0.05) after adjustment for gestational age.
      Multivariable linear regression analysis indicated significant positive
      associations between lumbar BMD of healthy children and the child's age and
      current weight, mother's weight gain during pregnancy, birth weight, children's
      outdoor activity duration and children's physical activity duration. CONCLUSION:
      Our study provides reference values of lumbar BMD for healthy Chinese children
      aged 0 to 3 years and identifies several influencing factors.

PMID- 24324753
TI  - Bayesian network analysis reveals alterations to default mode network
      connectivity in individuals at risk for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is associated with abnormal functioning of the default
      mode network (DMN). Functional connectivity (FC) changes to the DMN have been
      found in patients with amnestic mild cognitive impairment (aMCI), which is the
      prodromal stage of AD. However, whether or not aMCI also alters the effective
      connectivity (EC) of the DMN remains unknown. We employed a combined group
      independent component analysis (ICA) and Bayesian network (BN) learning approach
      to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17
      controls, in order to establish the EC pattern of DMN, and to evaluate changes
      occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence
      degree across DMN regions, which were organized into two closely interacting
      subsystems. Compared to controls, the aMCI group showed altered directed
      connectivity weights between DMN regions in the fronto-parietal, temporo-frontal,
      and temporo-parietal pathways. The aMCI group also exhibited altered regional
      convergence degree in the right inferior parietal lobule. Moreover, we found EC
      changes in DMN regions in aMCI were correlated with regional FC levels, and the
      connectivity metrics were associated with patients' cognitive performance. This
      study provides novel sights into our understanding of the functional architecture
      of the DMN and adds to a growing body of work demonstrating the importance of the
      DMN as a mechanism of aMCI. 

PMID- 24324754
TI  - Etoposide induces nuclear re-localisation of AID.
AB  - During B cell activation, the DNA lesions that initiate somatic hypermutation and
      class switch recombination are introduced by activation-induced cytidine
      deaminase (AID). AID is a highly mutagenic protein that is maintained in the
      cytoplasm at steady state, however AID is shuttled across the nuclear membrane
      and the protein transiently present in the nucleus appears sufficient for
      targeted alteration of immunoglobulin loci. AID has been implicated in epigenetic
      reprogramming in primordial germ cells and cell fusions and in induced
      pluripotent stem cells (iPS cells), however AID expression in non-B cells is very
      low. We hypothesised that epigenetic reprogramming would require a pathway that
      instigates prolonged nuclear residence of AID. Here we show that AID is
      completely re-localised to the nucleus during drug withdrawal following etoposide
      treatment, in the period in which double strand breaks (DSBs) are repaired. Re
      localisation occurs 2-6 hours after etoposide treatment, and AID remains in the
      nucleus for 10 or more hours, during which time cells remain live and motile. Re
      localisation is cell-cycle dependent and is only observed in G2. Analysis of DSB
      dynamics shows that AID is re-localised in response to etoposide treatment,
      however re-localisation occurs substantially after DSB formation and the levels
      of re-localisation do not correlate with gammaH2AX levels. We conclude that DSB
      formation initiates a slow-acting pathway which allows stable long-term nuclear
      localisation of AID, and that such a pathway may enable AID-induced DNA
      demethylation during epigenetic reprogramming. 

PMID- 24324755
TI  - Defective mitochondrial dynamics is an early event in skeletal muscle of an
      amyotrophic lateral sclerosis mouse model.
AB  - Mitochondria are dynamic organelles that constantly undergo fusion and fission to
      maintain their normal functionality. Impairment of mitochondrial dynamics is
      implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis
      (ALS) is an adult-onset neuromuscular degenerative disorder characterized by
      motor neuron death and muscle atrophy. ALS onset and progression clearly involve
      motor neuron degeneration but accumulating evidence suggests primary muscle
      pathology may also be involved. Here, we examined mitochondrial dynamics in live
      skeletal muscle of an ALS mouse model (G93A) harboring a superoxide dismutase
      mutation (SOD1(G93A)). Using confocal microscopy combined with overexpression of
      mitochondria-targeted photoactivatable fluorescent proteins, we discovered
      abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before
      disease onset. We further demonstrated that similar abnormalities in
      mitochondrial dynamics were induced by overexpression of mutant SOD1(G93A) in
      skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like
      muscle pathology in the absence of motor neuron degeneration. Mutant SOD1(G93A)
      forms aggregates inside muscle mitochondria and leads to fragmentation of the
      mitochondrial network as well as mitochondrial depolarization. Partial
      depolarization of mitochondrial membrane potential in normal muscle by carbonyl
      cyanide p-trifluoromethoxyphenylhydrazone (FCCP) caused abnormalities in
      mitochondrial dynamics similar to that in the SOD1(G93A) model muscle. A specific
      mitochondrial fission inhibitor (Mdivi-1) reversed the SOD1(G93A) action on
      mitochondrial dynamics, indicating SOD1(G93A) likely promotes mitochondrial
      fission process. Our results suggest that accumulation of mutant SOD1(G93A)
      inside mitochondria, depolarization of mitochondrial membrane potential and
      abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle
      pathology, which occurs early in the course of ALS and may actively promote ALS
      progression. 

PMID- 24324756
TI  - Public stigma against people with mental illness in the Gilgel Gibe Field
      Research Center (GGFRC) in Southwest Ethiopia.
AB  - BACKGROUND: Public understanding about mental illnesses and attitudes towards
      people with mental illness (PWMI) play a paramount role in the prevention and
      treatment of mental illness and the rehabilitation of PWMI. The aim of this study
      was to measure public stigma against PWMI and the factors associated with stigma
      in the Gilgel Gibe Field Research Center (GGFRC) in Southwest Ethiopia. METHODS:
      This community-based, cross-sectional study was conducted from June to August
      2012 among 845 randomly selected respondents by using the Community Attitudes
      towards the Mentally Ill (CAMI) scale, an interviewer-administered questionnaire.
      Data was entered with EPI-DATA and then exported to STATA for analysis. Simple
      descriptive and linear regression analyses were performed to identify predictors
      of stigma against PWMI. RESULTS: Of the total of 845 respondents, 68.17% were
      from rural districts. The mean stigma score was 2.62 on a 5-point score. The
      majority of the respondents (75.27%) believed that mental illness can be cured.
      Stress, poverty, and rumination were the most often perceived causes of mental
      illness. Rural residents had significantly higher stigma scores (std. beta =
      0.61, P<0.001). A statistically significant inverse relationship was found
      between the level of education and degree of stigma (std. beta = -0.14, P<0.01),
      while higher income was significantly associated with more stigma (std. beta =
      0.07, P<0.05). Respondents with higher scores for perceived supernatural causes
      (std. beta = -0.09, P<0.01) and perceived psychosocial and biological causes
      (std. beta = -0.14, P<0.001) had significantly lower stigma levels. CONCLUSIONS:
      The study found a more undermining but less avoidant attitude towards PWMI. Rural
      residents showed higher levels of stigma. Stigma against PWMI was lower in people
      with an explanatory concept about the causes of mental illness and a higher level
      of education. Information, education, and communication about the causes, signs,
      and nature of mental illnesses would help to reduce stigma.

PMID- 24324757
TI  - An intrinsic propensity of murine peritoneal B1b cells to switch to IgA in
      presence of TGF-beta and retinoic acid.
AB  - AIMS: In the present study we have investigated the comparative switching
      propensity of murine peritoneal and splenic B cell subpopulations to IgA in
      presence of retinoic acid (RA) and TGF-beta. METHODS AND RESULTS: To study the
      influence of RA and TGF-beta on switching of B cell subpopulations to IgA,
      peritoneal (B1a, B1b and B2 cells) and splenic (B1a, marginal zone, and B2) B
      cells from normal BALB/c mice were FACS purified, cultured for 4 days in presence
      of RA and TGF-beta and the number of IgA producing cells was determined by
      ELISPOT assay or FACS analysis. In presence of TGF-beta, peritoneal B1b cells
      switched to IgA more potently than other peritoneal B cell subpopulations. When
      TGF-beta was combined with retinoic acid (RA), switching to IgA was even more
      pronounced. Under these conditions, "innate" B cells like peritoneal and splenic
      B1 cells and MZ B cells produced IgA more readily than B2 cells. Additionally,
      high frequency of nucleotide exchanges indicating somatic hypermutation in VH
      regions was observed. Besides IgA induction, RA treatment of sorted PEC and
      splenic B cells led to expression of gut homing molecules - alpha4beta7 and CCR9.
      Intraperitoneal transfer of RA-treated B1 cells into Rag1(-/-) recipients
      resulted in IgA in serum and gut lavage, most efficiently amongst B1b cell
      recipients. CONCLUSION: Present study demonstrates the differential and
      synergistic effect of RA and TGF-beta on switching of different B cell
      subpopulations to IgA and establishes the prominence of peritoneal B1b cells in
      switching to IgA under the influence of these two factors. Our study extends our
      knowledge about the existing differences among B cell subpopulations with regards
      to IgA production and indicates towards their differential contribution to gut
      associated humoral immunity.

PMID- 24324759
TI  - SSW library: an SIMD Smith-Waterman C/C++ library for use in genomic
      applications.
AB  - BACKGROUND: The Smith-Waterman algorithm, which produces the optimal pairwise
      alignment between two sequences, is frequently used as a key component of fast
      heuristic read mapping and variation detection tools for next-generation
      sequencing data. Though various fast Smith-Waterman implementations are
      developed, they are either designed as monolithic protein database searching
      tools, which do not return detailed alignment, or are embedded into other tools.
      These issues make reusing these efficient Smith-Waterman implementations
      impractical. RESULTS: To facilitate easy integration of the fast Single
      Instruction-Multiple-Data Smith-Waterman algorithm into third-party software, we
      wrote a C/C++ library, which extends Farrar's Striped Smith-Waterman (SSW) to
      return alignment information in addition to the optimal Smith-Waterman score. In
      this library we developed a new method to generate the full optimal alignment
      results and a suboptimal score in linear space at little cost of efficiency. This
      improvement makes the fast Single-Instruction-Multiple-Data Smith-Waterman become
      really useful in genomic applications. SSW is available both as a C/C++ software
      library, as well as a stand-alone alignment tool at:
      https://github.com/mengyao/Complete-Striped-Smith-Waterman-Library. CONCLUSIONS:
      The SSW library has been used in the primary read mapping tool MOSAIK, the split
      read mapping program SCISSORS, the MEI detector TANGRAM, and the read-overlap
      graph generation program RZMBLR. The speeds of the mentioned software are
      improved significantly by replacing their ordinary Smith-Waterman or banded Smith
      Waterman module with the SSW Library.

PMID- 24324758
TI  - Development of an automated imaging pipeline for the analysis of the zebrafish
      larval kidney.
AB  - The analysis of kidney malformation caused by environmental influences during
      nephrogenesis or by hereditary nephropathies requires animal models allowing the
      in vivo observation of developmental processes. The zebrafish has emerged as a
      useful model system for the analysis of vertebrate organ development and
      function, and it is suitable for the identification of organotoxic or disease
      modulating compounds on a larger scale. However, to fully exploit its potential
      in high content screening applications, dedicated protocols are required allowing
      the consistent visualization of inner organs such as the embryonic kidney. To
      this end, we developed a high content screening compatible pipeline for the
      automated imaging of standardized views of the developing pronephros in zebrafish
      larvae. Using a custom designed tool, cavities were generated in agarose coated
      microtiter plates allowing for accurate positioning and orientation of zebrafish
      larvae. This enabled the subsequent automated acquisition of stable and
      consistent dorsal views of pronephric kidneys. The established pipeline was
      applied in a pilot screen for the analysis of the impact of potentially
      nephrotoxic drugs on zebrafish pronephros development in the Tg(wt1b:EGFP)
      transgenic line in which the developing pronephros is highlighted by GFP
      expression. The consistent image data that was acquired allowed for
      quantification of gross morphological pronephric phenotypes, revealing
      concentration dependent effects of several compounds on nephrogenesis. In
      addition, applicability of the imaging pipeline was further confirmed in a
      morpholino based model for cilia-associated human genetic disorders associated
      with different intraflagellar transport genes. The developed tools and pipeline
      can be used to study various aspects in zebrafish kidney research, and can be
      readily adapted for the analysis of other organ systems. 

PMID- 24324760
TI  - Transcriptome profiling analysis on whole bodies of microbial challenged
      Eriocheir sinensis larvae for immune gene identification and SNP development.
AB  - To study crab immunogenetics of individuals, newly hatched Eriocheir sinensis
      larvae were stimulated with a mixture of three pathogen strains (Gram-positive
      bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and
      fungi Pichia pastoris; 10(8) cfu.mL(-1)). A total of 44,767,566 Illumina clean
      reads corresponding to 4.52 Gb nucleotides were generated and assembled into
      100,252 unigenes (average length: 1,042 bp; range: 201-19,357 bp). 17,097
      (26.09%) of 65,535 non-redundant unigenes were annotated in NCBI non-redundant
      protein (Nr) database. Moreover, 23,188 (35.38%) unigenes were assigned to three
      Gene Ontology (GO) categories, 15,071 (23.00%) to twenty-six Clusters of
      orthologous Groups (COG) and 8,574 (13.08%) to six Kyoto Encyclopedia of Genes
      and Genomes (KEGG) pathways, respectively. Numerous genes were further identified
      to be associated with multiple immune pathways, including Toll, immune deficiency
      (IMD), janus kinase (JAK)-signal transducers and activators of transcription
      (STAT) and mitogen-activated protein kinase (MAPK) pathways. Some of them, such
      as tumor necrosis factor receptor associated factor 6 (TRAF6), fibroblast growth
      factor (FGF), protein-tyrosine phosphatase (PTP), JNK-interacting protein 1
      (JIP1), were first identified in E. sinensis. TRAF6 was even first discovered in
      crabs. Additionally, 49,555 single nucleotide polymorphisms (SNPs) were developed
      from over 13,309 unigenes. This is the first transcriptome report of whole bodies
      of E. sinensis larvae after immune challenge. Data generated here not only
      provide detail information to identify novel genes in genome reference-free E.
      sinensis, but also facilitate our understanding on host immunity and defense
      mechanism of the crab at whole transcriptome level. 

PMID- 24324761
TI  - Evidence of phenotypic and genetic relationships between sociality, emotional
      reactivity and production traits in Japanese quail.
AB  - The social behavior of animals, which is partially controlled by genetics, is one
      of the factors involved in their adaptation to large breeding groups. To
      understand better the relationships between different social behaviors, fear
      behaviors and production traits, we analyzed the phenotypic and genetic
      correlations of these traits in Japanese quail by a second generation crossing of
      two lines divergently selected for their social reinstatement behavior. Analyses
      of results for 900 individuals showed that the phenotypic correlations between
      behavioral traits were low with the exception of significant correlations between
      sexual behavior and aggressive pecks both at phenotypic (0.51) and genetic (0.90)
      levels. Significant positive genetic correlations were observed between emotional
      reactivity toward a novel object and sexual (0.89) or aggressive (0.63)
      behaviors. The other genetic correlations were observed mainly between behavioral
      and production traits. Thus, the level of emotional reactivity, estimated by the
      duration of tonic immobility, was positively correlated with weight at 17 and 65
      days of age (0.76 and 0.79, respectively) and with delayed egg laying onset
      (0.74). In contrast, a higher level of social reinstatement behavior was
      associated with an earlier egg laying onset (-0.71). In addition, a strong sexual
      motivation was correlated with an earlier laying onset (-0.68) and a higher
      number of eggs laid (0.82). A low level of emotional reactivity toward a novel
      object and also a higher aggressive behavior were genetically correlated with a
      higher number of eggs laid (0.61 and 0.58, respectively). These results bring new
      insights into the complex determinism of social and emotional reactivity
      behaviors in birds and their relationships with production traits. Furthermore,
      they highlight the need to combine animal welfare and production traits in
      selection programs by taking into account traits of sociability and emotional
      reactivity. 

PMID- 24324762
TI  - Decoy oligonucleotide rescues IGF1R expression from MicroRNA-223 suppression.
AB  - A mature miRNA generally suppresses hundreds of mRNA targets. To evaluate the
      selective effect of synthetic oligonucleotide decoys on hsa-miR-223 activity,
      reporters containing 3' untranslated regions (UTR) of IGF1R, FOXO1, POLR3G,
      FOXO3, CDC27, FBXW7 and PAXIP1 mRNAs were constructed for the luciferase assay.
      The oligonucleotide decoys were designed and synthesized according to mature miR
      223 sequence and its target mRNA sequence. Quantitative RT-PCR & western analysis
      were used to measure miR-223-targeted mRNA expression, Interestingly, apart from
      the antisense oligonucleotide, decoy nucleotides which were complementary to the
      5', central or 3' region of mature miR-223 suppressed miR-223 targeting the 3'UTR
      of IGF1R, FOXO1, FOXO3, CDC27, POLR3G, and FBXW7 mRNAs and rescued the expression
      of these genes to varying degrees from miR-223 suppression at both mRNA and
      protein levels. All decoys had no effect on PAXIP1 which was not targeted by miR
      223. The decoy 1 that was based on the sequence of IGF1R 3'UTR rescued the
      expression of IGF1R more significantly than other decoy nucleotides except the
      antisense decoy 4. Decoy 1 also rescued the expression of FOXO3 and POLR3G of
      which their 3'UTRs have similar binding sites for miR-223 with IGF1R 3'UTR.
      However decoy 1 failed to recover Sp1, CDC27 and FBXW7 expression. These data
      support that the sequence-specific decoy oligonucleotides might represent
      exogenous competing RNA which selectively inhibits microRNA targeting. 

PMID- 24324763
TI  - Severity assessment of lower respiratory tract infection in Malawi: derivation of
      a novel index (SWAT-Bp) which outperforms CRB-65.
AB  - OBJECTIVE: To assess the validity of CRB-65 (Confusion, Respiratory rate >30
      breaths/min, BP<90/60 mmHg, age >65 years) as a pneumonia severity index in a
      Malawian hospital population, and determine whether an alternative score has
      greater accuracy in this setting. DESIGN: Forty three variables were
      prospectively recorded during the first 48 hours of admission in all patients
      admitted to Queen Elizabeth Central Hospital, Malawi, for management of lower
      respiratory tract infection over a two month period (N = 240). Calculation of
      sensitivity and specificity for CRB-65 in predicting mortality was followed by
      multivariate modeling to create a score with superior performance in this
      population. RESULTS: Median age 37, HIV prevalence 79.9%, overall mortality
      18.3%. CRB-65 predicted mortality poorly, indicated by the area under the ROC
      curve of 0.649. Independent predictors of death were: Male sex, "S" (AOR 2.6);
      Wasting, "W" (AOR 6.6); non-ambulatory, "A" (AOR 2.5); Temp >38 degrees C or <35
      degrees C, "T" (AOR 3.2); BP<100/60, "Bp" (AOR 3.7). Combining these factors to
      form a severity index (SWAT-Bp) predicted mortality with high sensitivity and
      specificity (AUC: 0.867). Mortality for scores 0-5 was 0%, 3.3%, 7.4%, 29.2%,
      61.5% and 87.5% respectively. A score >=3 was 84% sensitive and 77% specific for
      mortality prediction, with a negative predictive value of 95.8%. CONCLUSION: CRB
      65 performs poorly in this population. The SWAT-Bp score can accurately stratify
      patients; <=2 indicates non-severe infection (mortality 4.4%) and >=3 severe
      illness (mortality 45%).

PMID- 24324764
TI  - Leaf morphology and ultrastructure responses to elevated O3 in transgenic Bt
      (cry1Ab/cry1Ac) rice and conventional rice under fully open-air field conditions.
AB  - BACKGROUND: Elevated tropospheric ozone severely affects not only yield but also
      the morphology, structure and physiological functions of plants. Because of
      concerns regarding the potential environmental risk of transgenic crops, it is
      important to monitor changes in transgenic insect-resistant rice under the
      projected high tropospheric ozone before its commercial release.
      METHODOLOGY/PRINCIPAL FINDINGS: Using a free-air concentration enrichment (FACE)
      system, we investigated the changes in leaf morphology and leaf ultrastructure of
      two rice varieties grown in plastic pots, transgenic Bt Shanyou 63 (Bt-SY63,
      carrying a fusion gene of cry1Ab and cry1Ac) and its non-transgenic counterpart
      (SY63), in elevated O3 (E-O3) versus ambient O3 (A-O3) after 64-DAS (Days after
      seeding), 85-DAS and 102-DAS. Our results indicated that E-O3 had no significant
      effects on leaf length, leaf width, leaf area, stomatal length and stomatal
      density for both Bt-SY63 and SY63. E-O3 increased the leaf thickness of Bt-SY63,
      but decreased that of SY63. O3 stress caused early swelling of the thylakoids of
      chloroplasts, a significant increase in the proportion of total plastoglobule
      area in the entire cell area (PCAP) and a significant decrease in the proportion
      of total starch grain area in the entire cell area (SCAP), suggesting that E-O3
      accelerated the leaf senescence of the two rice genotypes. Compared with SY63, E
      O3 caused early swelling of the thylakoids of chloroplasts and more substantial
      breakdown of chloroplasts in Bt-SY63. CONCLUSIONS/SIGNIFICANCE: Our results
      suggest that the incorporation of cry1Ab/Ac into SY63 could induce unintentional
      changes in some parts of plant morphology and that O3 stress results in greater
      leaf damage to Bt-SY63 than to SY63, with the former coupled with higher O3
      sensitivity in CCAP (the proportions of total chloroplast area in the entire cell
      area), PCAP and SCAP. This study provides valuable baseline information for the
      prospective commercial release of transgenic crops under the projected future
      climate.

PMID- 24324765
TI  - INDIGO - INtegrated data warehouse of microbial genomes with examples from the
      red sea extremophiles.
AB  - BACKGROUND: The next generation sequencing technologies substantially increased
      the throughput of microbial genome sequencing. To functionally annotate newly
      sequenced microbial genomes, a variety of experimental and computational methods
      are used. Integration of information from different sources is a powerful
      approach to enhance such annotation. Functional analysis of microbial genomes,
      necessary for downstream experiments, crucially depends on this annotation but it
      is hampered by the current lack of suitable information integration and
      exploration systems for microbial genomes. RESULTS: We developed a data warehouse
      system (INDIGO) that enables the integration of annotations for exploration and
      analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to
      construct complex queries and combine annotations from multiple sources starting
      from genomic sequence to protein domain, gene ontology and pathway levels. This
      data warehouse is aimed at being populated with information from genomes of pure
      cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently,
      INDIGO contains information from Salinisphaera shabanensis, Haloplasma
      contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea
      anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to
      gain new insights into specific aspects on the unique lifestyle and adaptations
      of these organisms to extreme environments. CONCLUSIONS: We developed a data
      warehouse system, INDIGO, which enables comprehensive integration of information
      from various resources to be used for annotation, exploration and analysis of
      microbial genomes. It will be regularly updated and extended with new genomes. It
      is aimed to serve as a resource dedicated to the Red Sea microbes. In addition,
      through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG)
      pipeline. The INDIGO web server is freely available at
      http://www.cbrc.kaust.edu.sa/indigo.

PMID- 24324766
TI  - Adaptive visual re-weighting in children's postural control.
AB  - This study investigated how children's postural control adapts to changes in the
      visual environment and whether they use previous experience to adjust postural
      responses to following expositions. Four-, eight-, and twelve-year-old children
      (10 in each group) and 10 young adults stood upright inside of a moving room
      during eight trials each lasting one-minute. In the first trial, the room was
      stationary. In the following seven trials, the room oscillated at 0.2 Hz,
      amplitude of 0.5 cm, with the exception of the fifth trial, in which the room
      oscillated with amplitude of 3.2 cm. Body sway responses of young adults and
      older children down-weighted more to the increased visual stimulus amplitude when
      compared to younger children. In addition, four- and eight-year-old children
      quickly up-weighted body responses to visual stimulus in the subsequent two
      trials after the high amplitude trial. Sway variability decreased with age and
      was greatest during the high-amplitude trial. These results indicate that four
      year olds have already developed the adaptive capability to quickly down-weight
      visual influences. However, the increased gain values and residual variability
      observed for the younger children suggest that they have not fully calibrated
      their adaptive response to that of the young adults tested. Moreover, younger
      children do not carry over their previous experience from the sensorial
      environment to adapt to future changes. 

PMID- 24324767
TI  - Trans-lamina cribrosa pressure difference and open-angle glaucoma. The central
      India eye and medical study.
AB  - PURPOSE: To assess associations of the trans-lamina cribrosa pressure difference
      (TLCPD) with glaucomatous optic neuropathy. METHODS: The population-based Central
      India Eye and Medical Study included 4711 subjects. Based on a previous study
      with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated
      as CSFP[mmHg] = 0.44 Body Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]
      0.18*Age[Years] -1.91. TLCPD was IOP-CSFP. RESULTS: Mean TLCPD was 3.64+/-4.25 mm
      Hg in the non-glaucomatous population and 9.65+/-8.17 mmHg in the glaucomatous
      group. In multivariate analysis, TLCPD was associated with older age (P<0.001;
      standardized coefficient beta:0.53; regression coefficient B:0.18; 95% confidence
      interval (CI):0.17, 0.18), lower body mass index (P<0.001; beta: -0.28; B: -0.36;
      95%CI: -0.38, -0.31), lower diastolic blood pressure (P<0.001; beta: -0.31; B: 
      0.12; 95%CI: -0.13, -0.11), higher pulse (P<0.001; beta:0.05; B:0.02;
      95%CI:0.01,0.2), lower body height (P = 0.02; beta: -0.02; B: -0.01; 95%CI: 
      0.02,0.00), higher educational level (P<0.001; beta:0.04; B:0.15;
      95%CI:0.09,0.22), higher cholesterol blood concentrations (P<0.001; beta:0.04;
      B:0.01; 95%CI:0.01,0.01), longer axial length (P = 0.006; beta:0.03; B:0.14;
      95%CI:0.04,0.24), thicker central cornea (P<0.001; beta:0.15; B:0.02;
      95%CI:0.02,0.02), higher corneal refractive power (P<0.001; beta:0.07; B:0.18;
      95%CI:0.13,0.23) and presence of glaucomatous optic neuropathy (P<0.001;
      beta:0.11; B:3.43; 95%CI:2.96,3.99). Differences between glaucomatous subjects
      and non-glaucomatous subjects in CSFP were more pronounced for open-angle
      glaucoma (OAG) than for angle-closure glaucoma (ACG) (3.0 mmHg versus 1.8 mmHg),
      while differences between glaucomatous subjects and non-glaucomatous subjects in
      IOP were higher for ACG than for OAG (8.5 mmHg versus 3.0 mmHg). Presence of OAG
      was significantly associated with TLCPD (P<0.001; OR:1.24; 95%CI:1.19,1.29) but
      not with IOP (P = 0.08; OR:0.96; 95%CI:0.91,1.00). Prevalence of ACG was
      significantly associated with IOP (P = 0.04; OR:1.19; 95%CI:1.01,1.40) but not
      with TLCPD (P = 0.92). CONCLUSIONS: In OAG, but not in ACG, calculated TLCPD
      versus IOP showed a better association with glaucoma presence and amount of
      glaucomatous optic neuropathy. It supports the notion of a potential role of low
      CSFP in the pathogenesis of open-angle glaucoma.

PMID- 24324768
TI  - Modeling the distribution of Geodia sponges and sponge grounds in the Northwest
      Atlantic.
AB  - Deep-sea sponge grounds provide structurally complex habitat for fish and
      invertebrates and enhance local biodiversity. They are also vulnerable to bottom
      contact fisheries and prime candidates for Vulnerable Marine Ecosystem
      designation and related conservation action. This study uses species distribution
      modeling, based on presence and absence observations of Geodia spp. and sponge
      grounds derived from research trawl catches, as well as spatially continuous data
      on the physical and biological ocean environment derived from satellite data and
      oceanographic models, to model the distribution of Geodia sponges and sponge
      grounds in the Northwest Atlantic. Most models produce excellent fits with
      validation data although fits are reduced when models are extrapolated to new
      areas, especially when oceanographic regimes differ between areas. Depth and
      minimum bottom salinity were important predictors in most models, and a Geodia
      spp. minimum bottom salinity tolerance threshold in the 34.3-34.8 psu range was
      hypothesized on the basis of model structure. The models indicated two currently
      unsampled regions within the study area, the deeper parts of Baffin Bay and the
      Newfoundland and Labrador slopes, where future sponge grounds are most likely to
      be found. 

PMID- 24324769
TI  - 3D-printed microwell arrays for Ciona microinjection and timelapse imaging.
AB  - Ascidians such as Ciona are close chordate relatives of the vertebrates with
      small, simple embryonic body plans and small, simple genomes. The tractable size
      of the embryo offers considerable advantages for in toto imaging and quantitative
      analysis of morphogenesis. For functional studies, Ciona eggs are considerably
      more challenging to microinject than the much larger eggs of other model
      organisms such as zebrafish and Xenopus. One of the key difficulties is in
      restraining the eggs so that the microinjection needle can be easily introduced
      and withdrawn. Here we develop and test a device to cast wells in agarose that
      are each sized to hold a single egg. This injection mold is fabricated by micro
      resolution stereolithography with a grid of egg-sized posts that cast
      corresponding wells in agarose. This 3D printing technology allows the rapid and
      inexpensive testing of iteratively refined prototypes. In addition to their
      utility in microinjection, these grids of embryo-sized wells are also valuable
      for timelapse imaging of multiple embryos. 

PMID- 24324770
TI  - Effect of geolocators on migration and subsequent breeding performance of a long
      distance passerine migrant.
AB  - Geolocators are small light-weight data loggers used to track individual
      migratory routes, and their use has increased exponentially in birds. However,
      the effects of geolocators on individual performance are still poorly known. We
      studied geolocator effects on a long-distance migrating passerine bird, the
      northern wheatear (Oenanthe oenanthe L.). We asked the general question of
      whether geolocators affect migratory behaviour and subsequent reproductive
      performance of small passerines by comparing arrival time, breeding time,
      breeding success and survival of geolocator versus control birds of known
      identity and breeding history. During two years geolocator birds (n=37) displayed
      a lower apparent survival (30%) as compared to controls (45%, n=164).
      Furthermore, returning geolocator birds (n=12) arrived on average 3.5 days later,
      started laying eggs 6.3 days later, and had lower nest success (25%) than control
      birds (78%). Our results suggest that geolocators affect migratory performance
      with carry-over effects to the timing of breeding and reproductive success in the
      subsequent breeding season. We discuss the implications of such geolocator
      effects for the study of migratory strategies of small passerines in general and
      suggest how to identify and investigate such effects in the future. 

PMID- 24324771
TI  - The external validity of randomized controlled trials of hypertension within
      China: from the perspective of sample representation.
AB  - OBJECTIVE: To explore external validity of randomized controlled trials (RCTs) of
      hypertension within China from the view of sample representation. METHODS:
      Comprehensive literature searches were performed in Medline, Embase, Cochrane
      Central Register of Controlled Trials (CCTR) et al and advanced search strategies
      were used to locate hypertension RCTs as well as observational studies conducted
      in China during 1996 to 2009 synchronously. The risk of bias in RCTs and
      observational studies was assessed by two modified scales respectively, and then
      both types of studies with 3 or more grading scores were included for the purpose
      of evaluating of external validity. Following that the study characteristics
      relative to sample representation were extracted from RCTs and observational
      studies synchronously, and the later were taken as external references for
      validating sample representation of RCTs. RESULTS: 226 hypertension RCTs and 21
      observational studies were included for final analysis. Comparing samples with
      observational studies, the mean age of samples within RCTs was 54.46 years,
      significantly lower than that of observational studies (66.35 years) (P=0.002).
      The average disease course in patients of RCTs was 3.89 years and grade III
      hypertensive patients accounted for 17%; both were lower than that of the
      observational studies (12.96 years, P<0.001; 34%, P=0.026 respectively). In
      addition, the proportions of patients with complications due to heart failure,
      stroke, diabetes, or coronary heart disease in RCTs were 8%, 5%, 12% and 11%
      correspondingly, all of which were significantly less than that of observational
      studies (11%, 18%, 17% and 29%). CONCLUSION: Sample characteristics within
      hypertension RCTs were significantly different from those in observational
      studies. The samples in most RCTs were under-represented. It's feasible to take
      samples of observational studies as a mirror of the actual composition of
      hypertension patients in the real world, if the reporting of observational
      studies is abundant and available.

PMID- 24324772
TI  - The maize glossy13 gene, cloned via BSR-Seq and Seq-walking encodes a putative
      ABC transporter required for the normal accumulation of epicuticular waxes.
AB  - Aerial plant surfaces are covered by epicuticular waxes that among other purposes
      serve to control water loss. Maize glossy mutants originally identified by their
      "glossy" phenotypes exhibit alterations in the accumulation of epicuticular
      waxes. By combining data from a BSR-Seq experiment and the newly developed Seq
      Walking technology, GRMZM2G118243 was identified as a strong candidate for being
      the glossy13 gene. The finding that multiple EMS-induced alleles contain
      premature stop codons in GRMZM2G118243, and the one knockout allele of gl13,
      validates the hypothesis that gene GRMZM2G118243 is gl13. Consistent with this,
      GRMZM2G118243 is an ortholog of AtABCG32 (Arabidopsis thaliana), HvABCG31
      (barley) and OsABCG31 (rice), which encode ABCG subfamily transporters involved
      in the trans-membrane transport of various secondary metabolites. We therefore
      hypothesize that gl13 is involved in the transport of epicuticular waxes onto the
      surfaces of seedling leaves. 

PMID- 24324773
TI  - Bayesian networks for clinical decision support in lung cancer care.
AB  - Survival prediction and treatment selection in lung cancer care are characterised
      by high levels of uncertainty. Bayesian Networks (BNs), which naturally reason
      with uncertain domain knowledge, can be applied to aid lung cancer experts by
      providing personalised survival estimates and treatment selection
      recommendations. Based on the English Lung Cancer Database (LUCADA), we evaluate
      the feasibility of BNs for these two tasks, while comparing the performances of
      various causal discovery approaches to uncover the most feasible network
      structure from expert knowledge and data. We show first that the BN structure
      elicited from clinicians achieves a disappointing area under the ROC curve of
      0.75 (+/- 0.03), whereas a structure learned by the CAMML hybrid causal discovery
      algorithm, which adheres with the temporal restrictions, achieves 0.81 (+/-
      0.03). Second, our causal intervention results reveal that BN treatment
      recommendations, based on prescribing the treatment plan that maximises survival,
      can only predict the recorded treatment plan 29% of the time. However, this
      percentage rises to 76% when partial matches are included. 

PMID- 24324774
TI  - Optic nerve head blood flow autoregulation during changes in arterial blood
      pressure in healthy young subjects.
AB  - AIM: In the present study the response of optic nerve head blood flow to an
      increase in ocular perfusion pressure during isometric exercise was studied.
      Based on our previous studies we hypothesized that subjects with an abnormal
      blood flow response, defined as a decrease in blood flow of more than 10% during
      or after isometric exercise, could be identified. METHODS: A total of 40 healthy
      subjects were included in this study. Three periods of isometric exercise were
      scheduled, each consisting of 2 minutes of handgripping. Optic nerve head blood
      flow was measured continuously before, during and after handgripping using laser
      Doppler flowmetry. Blood pressure was measured non-invasively in one-minute
      intervals. Intraocular pressure was measured at the beginning and the end of the
      measurements and ocular perfusion pressure was calculated as 2/3*mean arterial
      pressure -intraocular pressure. RESULTS: Isometric exercise was associated with
      an increase in ocular perfusion pressure during all handgripping periods (p <
      0.001). By contrast no change in optic nerve head blood flow was seen. However,
      in a subgroup of three subjects blood flow showed a consistent decrease of more
      than 10% during isometric exercise although their blood pressure values
      increased. In addition, three other subjects showed a consistent decline of blood
      flow of more than 10% during the recovery periods. CONCLUSION: Our data confirm
      previous results indicating that optic nerve head blood flow is autoregulated
      during an increase in perfusion pressure. In addition, we observed a subgroup of
      6 subjects (15%) that showed an abnormal response, which is in keeping with our
      previous data. The mechanisms underlying this abnormal response remain to be
      shown.

PMID- 24324775
TI  - Changes of plasma B-type natriuretic peptide levels after high-pressure post
      dilation following coronary stent deployment.
AB  - OBJECTIVE: To evaluate the changes of plasma B-type natriuretic peptide(BNP)
      levels after high-pressure post-dilation following coronary stent deployment.
      METHODS: A total of 173 patients undergoing percutaneous coronary intervention
      for the left anterior descending artery were enrolled into the study. All
      patients were divided into two groups: the conventional group and the post
      dilation group. The plasma BNP, troponin I(TnI), myocardial band isoenzyme of
      creatine kinase(CK-MB) levels and the serum high sensitive C-reactive protein(hs
      CRP) levels immediately before and 24 hours after the interventional procedures
      were compared between the two groups. RESULTS: There were no significant
      differences between the two groups in terms of clinical features, clinical and
      biochemical parameters, stent parameters, pre-procedural plasma BNP and TnI
      levels, pre-procedural serum hs-CRP levels, as well as pre- and post-procedural
      CK-MB levels (all P>0.05). In the conventional group, post-procedural plasma BNP
      levels were significantly reduced when compared with the pre-procedural levels,
      median(25th,75th) were 32.5 ng/L(15.0,52.4) vs. 37.7 ng/L(18.2,67.3), P = 0.001.
      In the post-dilation group, post-procedural plasma BNP levels were significantly
      increased when compared with the pre-procedural levels, median(25th,75th) were
      53.5 ng/L(29.6,82.8) vs. 44.2 ng/L(17.15,70.7), P<0.0001. Post-procedural plasma
      TnI levels were also significantly increased when compared with the pre
      procedural levels in both groups, median(25th,75th) were 0.02 ng/L(0.01,0.08) vs.
      0.01 ng/L(0.01,0.01), 0.05 ng/L(0.01,0.35) vs. 0.01 ng/L(0.01,0.01),
      respectively, P<0.0001, so were the serum hs-CRP levels, median(25th,75th) were
      3.3 mg/L(2.4,4.7) vs. 2.2 mg/L(1.4,3.3), 4.2 mg/L(3.175,5.825) vs. 2.3
      mg/L(1.45,3.6), respectively, P<0.0001. Post-procedural plasma BNP, TnI and serum
      hs-CRP levels in the post-dilation group were significantly higher than those in
      the conventional group(all P<0.0001). CONCLUSION: High-pressure post-dilation
      following coronary stent deployment resulted in a significant increase of plasma
      BNP levels, as well as plasma TnI levels and serum hs-CRP levels, which may be
      related to myocardial perfusion, more myocardial injury and more inflammation.

PMID- 24324776
TI  - Forest loss and the biodiversity threshold: an evaluation considering species
      habitat requirements and the use of matrix habitats.
AB  - Habitat loss is the main driver of the current biodiversity crisis, a landscape
      scale process that affects the survival of spatially-structured populations.
      Although it is well-established that species responses to habitat loss can be
      abrupt, the existence of a biodiversity threshold is still the cause of much
      controversy in the literature and would require that most species respond
      similarly to the loss of native vegetation. Here we test the existence of a
      biodiversity threshold, i.e. an abrupt decline in species richness, with habitat
      loss. We draw on a spatially-replicated dataset on Atlantic forest small mammals,
      consisting of 16 sampling sites divided between forests and matrix habitats in
      each of five 3600-ha landscapes (varying from 5% to 45% forest cover), and on an
      a priori classification of species into habitat requirement categories (forest
      specialists, habitat generalists and open-area specialists). Forest specialists
      declined abruptly below 30% of forest cover, and spillover to the matrix occurred
      only in more forested landscapes. Generalists responded positively to landscape
      heterogeneity, peaking at intermediary levels of forest cover. Open area
      specialists dominated the matrix and did not spillover to forests. As a result of
      these distinct responses, we observed a biodiversity threshold for the small
      mammal community below 30% forest cover, and a peak in species richness just
      above this threshold. Our results highlight that cross habitat spillover may be
      asymmetrical and contingent on landscape context, occurring mainly from forests
      to the matrix and only in more forested landscapes. Moreover, they indicate the
      potential for biodiversity thresholds in human-modified landscapes, and the
      importance of landscape heterogeneity to biodiversity. Since forest loss affected
      not only the conservation value of forest patches, but also the potential for
      biodiversity-mediated services in anthropogenic habitats, our work indicates the
      importance of proactive measures to avoid human-modified landscapes to cross this
      threshold. 

PMID- 24324777
TI  - The relationship between membrane potential and calcium dynamics in glucose
      stimulated beta cell syncytium in acute mouse pancreas tissue slices.
AB  - Oscillatory electrical activity is regarded as a hallmark of the pancreatic beta
      cell glucose-dependent excitability pattern. Electrophysiologically recorded
      membrane potential oscillations in beta cells are associated with in-phase
      oscillatory cytosolic calcium activity ([Ca(2+)]i) measured with fluorescent
      probes. Recent high spatial and temporal resolution confocal imaging revealed
      that glucose stimulation of beta cells in intact islets within acute tissue
      slices produces a [Ca(2+)]i change with initial transient phase followed by a
      plateau phase with highly synchronized [Ca(2+)]i oscillations. Here, we aimed to
      correlate the plateau [Ca(2+)]i oscillations with the oscillations of membrane
      potential using patch-clamp and for the first time high resolution voltage
      sensitive dye based confocal imaging. Our results demonstrated that the glucose
      evoked membrane potential oscillations spread over the islet in a wave-like
      manner, their durations and wave velocities being comparable to the ones for
      [Ca(2+)]i oscillations and waves. High temporal resolution simultaneous records
      of membrane potential and [Ca(2+)]i confirmed tight but nevertheless limited
      coupling of the two processes, with membrane depolarization preceding the
      [Ca(2+)]i increase. The potassium channel blocker tetraethylammonium increased
      the velocity at which oscillations advanced over the islet by several-fold while,
      at the same time, emphasized differences in kinetics of the membrane potential
      and the [Ca(2+)]i. The combination of both imaging techniques provides a powerful
      tool that will help us attain deeper knowledge of the beta cell network. 

PMID- 24324778
TI  - GABAA receptor in the thalamic specific relay system contributes to the propofol
      induced somatosensory cortical suppression in rat.
AB  - Interaction with the gamma-aminobutyric-acid-type-A (GABAA) receptors is
      recognized as an important component of the mechanism of propofol, a sedative
      hypnotic drug commonly used as anesthetic. However the contribution of GABAA
      receptors to the central nervous system suppression is still not well understood,
      especially in the thalamocortical network. In the present study, we investigated
      if intracerebral injection of bicuculline (a GABAA receptor antagonist) into the
      thalamus ventral posteromedial nucleus (VPM, a thalamus specific relay nuclei
      that innervated S1 mostly) could reverse propofol-induced cortical suppression,
      through recording the changes of both spontaneous and somatosensory neural
      activities in rat's somatosensory cortex (S1). We found that after injection of
      bicuculline into VPM, significant increase of neural activities were observed in
      all bands of local field potentials (total band, 182+/-6%), while the amplitude
      of all components in somatosensory evoked potentials were also increased
      (negative, 121+/-9% and positive, 124+/-6%).These data support that the
      potentiation of GABAA receptor-mediated synaptic inhibition in a thalamic
      specific relay system seems to play a crucial role in propofol-induced cortical
      suppression in the somatosensory cortex of rats. 

PMID- 24324779
TI  - Enzyme-linked immunosorbent assay characterization of basal variation and
      heritability of systemic microfibrillar-associated protein 4.
AB  - BACKGROUND: Microfibrillar-associated protein 4 (MFAP4) is a systemic biomarker
      that is significantly elevated in samples from patients suffering from hepatic
      cirrhosis. The protein is generally localized to elastic fibers and other
      connective tissue fibers in the extracellular matrix (ECM), and variation in
      systemic MFAP4 (sMFAP4) has the potential to reflect diverse diseases with
      increased ECM turnover. Here, we aimed to validate an enzyme-linked immunosorbent
      assay (ELISA) for the measurement of sMFAP4 with an emphasis on the robustness of
      the assay. Moreover, we aimed to determine confounders influencing the basal
      sMFAP4 variability and the genetic contribution to the basal variation. METHODS:
      The sandwich ELISA was based on two monoclonal anti-MFAP4 antibodies and was
      optimized and calibrated with a standard of recombinant MFAP4. The importance of
      pre-analytical sample handling was evaluated regarding sample tube type, time,
      and temperature conditions. The mean value structure and variance structure was
      determined in a twin cohort including 1,417 Danish twins (age 18-67 years) by
      mixed-effect linear regression modeling. RESULTS: The practical working range of
      the sandwich ELISA was estimated to be 4-75 U/ml. The maximum intra- and inter
      assay variation was estimated to be 8.7% and 6.6%, respectively. Sample handling
      and processing appeared to influence MFAP4 measurements only marginally. The
      average concentration of sMFAP4 in the serum was 18.9 +/- 8.4 (SD) U/ml in the
      twin cohort (95% CI: 18.5-19.4, median sMFAP4 17.3 U/ml). The mean structure
      model was demonstrated to include waist-hip ratio, age, and cigarette smoking
      status in interactions with gender. A relatively low heritability of h(2) = 0.24
      was found after applying a model including additive genetic factors and shared
      and non-shared environmental factors. CONCLUSIONS: The described ELISA provides
      robust measures of the liver fibrosis marker sMFAP4. The low heritability and the
      relatively limited basal variation suggest that increased sMFAP4 reflects disease
      induced processes.

PMID- 24324780
TI  - The sound of danger: threat sensitivity to predator vocalizations, alarm calls,
      and novelty in gulls.
AB  - The threat sensitivity hypothesis predicts that organisms will evaluate the
      relative danger of and respond differentially to varying degrees of predation
      threat. Doing so allows potential prey to balance the costs and benefits of anti
      predator behaviors. Threat sensitivity has undergone limited testing in the
      auditory modality, and the relative threat level of auditory cues from different
      sources is difficult to infer across populations when variables such as
      background risk and experience are not properly controlled. We experimentally
      exposed a single population of two sympatric gull species to auditory stimuli
      representing a range of potential threats in order to compare the relative threat
      of heterospecific alarm calls, conspecific alarms calls, predator vocalizations,
      and novel auditory cues. Gulls were able to discriminate among a diverse set of
      threat indicators and respond in a graded manner commensurate with the level of
      threat. Vocalizations of two potential predators, the human voice and bald eagle
      call, differed in their threat level compared to each other and to alarm calls.
      Conspecific alarm calls were more threatening than heterospecfic alarm calls to
      the larger great black-backed gull, but the smaller herring gull weighed both
      equally. A novel cue elicited a response intermediate between known threats and a
      known non-threat in herring gulls, but not great black-backed gulls. Our results
      show that the relative threat level of auditory cues from different sources is
      highly species-dependent, and that caution should be exercised when comparing
      graded and threshold threat sensitive responses. 

PMID- 24324781
TI  - Brain's reward circuits mediate itch relief. a functional MRI study of active
      scratching.
AB  - Previous brain imaging studies investigating the brain processing of scratching
      used an exogenous intervention mimicking scratching, performed not by the
      subjects themselves, but delivered by an investigator. In real life, scratching
      is a conscious, voluntary, controlled motor response to itching, which is
      directed to the perceived site of distress. In this study we aimed to visualize
      in real-time by brain imaging the core mechanisms of the itch-scratch cycle when
      scratching was performed by subjects themselves. Secondly, we aimed to assess the
      correlations between brain patterns of activation and psychophysical ratings of
      itch relief or pleasurability of scratching. We also compared the patterns of
      brain activity evoked by self-scratching vs. passive scratching. We used a robust
      tridimensional Arterial Spin Labeling fMRI technique that is less sensitive to
      motion artifacts: 3D gradient echo and spin echo (GRASE)--Propeller. Active
      scratching was accompanied by a higher pleasurability and induced a more
      pronounced deactivation of the anterior cingulate cortex and insula, in
      comparison with passive scratching. A significant involvement of the reward
      system including the ventral tegmentum of the midbrain, coupled with a mechanism
      deactivating the periaqueductal gray matter (PAG), suggests that itch modulation
      operates in reverse to the mechanism known to suppress pain. Our findings not
      only confirm a role for the central networks processing reward in the pleasurable
      aspects of scratching, but also suggest they play a role in mediating itch
      relief.

PMID- 24324782
TI  - Stable isotopes provide insight into population structure and segregation in
      eastern North Atlantic sperm whales.
AB  - In pelagic species inhabiting large oceans, genetic differentiation tends to be
      mild and populations devoid of structure. However, large cetaceans have provided
      many examples of structuring. Here we investigate whether the sperm whale, a
      pelagic species with large population sizes and reputedly highly mobile, shows
      indication of structuring in the eastern North Atlantic, an ocean basin in which
      a single population is believed to occur. To do so, we examined stable isotope
      values in sequential growth layer groups of teeth from individuals sampled in
      Denmark and NW Spain. In each layer we measured oxygen- isotope ratios
      (delta(18)O) in the inorganic component (hydroxyapatite), and nitrogen and carbon
      isotope ratios (delta(15)N: delta(13)C) in the organic component (primarily
      collagenous). We found significant differences between Denmark and NW Spain in
      delta(15)N and delta(18)O values in the layer deposited at age 3, considered to
      be the one best representing the baseline of the breeding ground, in delta(15)N,
      delta(13)C and delta(18)O values in the period up to age 20, and in the
      ontogenetic variation of delta(15)N and delta(18)O values. These differences
      evidence that diet composition, use of habitat and/or migratory destinations are
      dissimilar between whales from the two regions and suggest that the North
      Atlantic population of sperm whales is more structured than traditionally
      accepted. 

PMID- 24324783
TI  - Function and distribution of 5-HT2 receptors in the honeybee (Apis mellifera).
AB  - BACKGROUND: Serotonin plays a pivotal role in regulating and modulating
      physiological and behavioral processes in both vertebrates and invertebrates. In
      the honeybee (Apis mellifera), serotonin has been implicated in division of
      labor, visual processing, and learning processes. Here, we present the cloning,
      heterologous expression, and detailed functional and pharmacological
      characterization of two honeybee 5-HT2 receptors. METHODS: Honeybee 5-HT2
      receptor cDNAs were amplified from brain cDNA. Recombinant cell lines were
      established constitutively expressing receptor variants. Pharmacological
      properties of the receptors were investigated by Ca(2+) imaging experiments.
      Quantitative PCR was applied to explore the expression patterns of receptor
      mRNAs. RESULTS: The honeybee 5-HT2 receptor class consists of two subtypes, Am5
      HT2alpha and Am5-HT2beta. Each receptor gene also gives rise to alternatively
      spliced mRNAs that possibly code for truncated receptors. Only activation of the
      full-length receptors with serotonin caused an increase in the intracellular
      Ca(2+) concentration. The effect was mimicked by the agonists 5-methoxytryptamine
      and 8-OH-DPAT at low micromolar concentrations. Receptor activities were blocked
      by established 5-HT receptor antagonists such as clozapine, methiothepin, or
      mianserin. High transcript numbers were detected in exocrine glands suggesting
      that 5-HT2 receptors participate in secretory processes in the honeybee.
      CONCLUSIONS: This study marks the first molecular and pharmacological
      characterization of two 5-HT2 receptor subtypes in the same insect species. The
      results presented should facilitate further attempts to unravel central and
      peripheral effects of serotonin mediated by these receptors.

PMID- 24324785
TI  - Effects of natural and human-assisted regeneration on landscape dynamics in a
      Korean pine forest in Northeast China.
AB  - Improper forest harvesting can potentially degrade forest ecosystem functions and
      services. Human-assisted regeneration (e.g., planting) is often used to increase
      the rate of forest recovery and thereby reduce regeneration failure. Seed
      dispersal is a fundamental ecological process that can also influence spatio
      temporal patterns of forest regeneration. In this study, we investigated the
      relative contribution of planting and seed dispersal on forest regeneration at
      landscape scales. Because such influences can be further complicated by timber
      harvest intensity and seed availability within and around harvested area, we also
      evaluated the effects of those factors on forest landscape dynamics. We used the
      forest landscape model LANDIS to simulate the dynamics of Korean pine-broadleaf
      mixed forests in Northeast China. We considered three factors: timber harvest
      intensity (3 levels), seed dispersal and whether or not planting was used. The
      results showed that planting was more important in maintaining the abundance of
      Korean pine (Pinus koraiensis), a climax keystone species in this region, under
      the high-intensity harvesting option during early succession. In contrast, seed
      dispersal was more important during late succession. Korean pine can be
      successfully regenerated through seed dispersal under low and medium harvest
      intensities. Our results also indicated that effective natural regeneration will
      require protecting seed-production trees (seed rain). This study results provide
      a basis for more effectively managing Chinese temperate forests and possibly
      other similar ecosystems. 

PMID- 24324784
TI  - The combined expression patterns of Ikaros isoforms characterize different
      hematological tumor subtypes.
AB  - A variety of genetic alterations are considered hallmarks of cancer development
      and progression. The Ikaros gene family, encoding for key transcription factors
      in hematopoietic development, provides several examples as genetic defects in
      these genes are associated with the development of different types of leukemia.
      However, the complex patterns of expression of isoforms in Ikaros family genes
      has prevented their use as clinical markers. In this study, we propose the use of
      the expression profiles of the Ikaros isoforms to classify various hematological
      tumor diseases. We have standardized a quantitative PCR protocol to estimate the
      expression levels of the Ikaros gene exons. Our analysis reveals that these
      levels are associated with specific types of leukemia and we have found
      differences in the levels of expression relative to five interexonic Ikaros
      regions for all diseases studied. In conclusion, our method has allowed us to
      precisely discriminate between B-ALL, CLL and MM cases. Differences between the
      groups of lymphoid and myeloid pathologies were also identified in the same way. 

PMID- 24324786
TI  - Elevation, temperature, and aquatic connectivity all influence the infection
      dynamics of the amphibian chytrid fungus in adult frogs.
AB  - Infectious diseases can cause population declines and even extinctions. The
      amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), has caused
      population declines and extinctions in amphibians on most continents. In the
      tropics, research on the dynamics of this disease has focused on amphibian
      populations in mountainous areas. In most of these areas, high and low elevation
      sites are connected by an assemblage of streams that may transport the infectious
      stage of the pathogen from high to low elevations, and, also, this pathogen,
      which grows well at cool temperatures, may persist better in cooler water flowing
      from high elevations. Thus, the dynamics of disease at low elevation sites
      without aquatic connections to higher elevation sites, i.e., non-contiguous low
      elevation sites, may differ from dynamics at contiguous low elevation sites. We
      sampled adult common mistfrogs (Litoria rheocola) at six sites of three types:
      two at high (> 400 m) elevations, two at low elevations contiguous with high
      elevation streams, and two at low elevations non-contiguous with any high
      elevation site. Adults were swabbed for Bd diagnosis from June 2010 to June 2011
      in each season, over a total of five sampling periods. The prevalence of Bd
      fluctuated seasonally and was highest in winter across all site types. Site type
      significantly affected seasonal patterns of prevalence of Bd. Prevalence remained
      well above zero throughout the year at the high elevation sites. Prevalence
      declined to lower levels in contiguous low sites, and reached near-zero at non
      contiguous low sites. Patterns of air temperature fluctuation were very similar
      at both the low elevation site types, suggesting that differences in water
      connectivity to high sites may have affected the seasonal dynamics of Bd
      prevalence between contiguous and non-contiguous low elevation site types. Our
      results also suggest that reservoir hosts may be important in the persistence of
      disease at low elevations.

PMID- 24324787
TI  - Longitudinal assessment of optical quality and intraocular scattering using the
      double-pass instrument in normal eyes and eyes with short tear breakup time.
AB  - PURPOSE: To assess the longitudinal changes in optical quality including
      intraocular scattering in normal eyes and eyes with short tear breakup time
      (TBUT). METHODS: We prospectively examined twenty eyes of 20 healthy subjects,
      and age-matched twenty eyes of 20 short TBUT subjects. The modulation transfer
      function (MTF) cutoff frequency, the Strehl ratio, and the objective scattering
      index (OSI) were quantitatively assessed using an Optical Quality Analysis
      System. We investigated the changes in these variables measured consecutively at
      the initial examination, 5, and 10 seconds without blinking. We also compared
      these variables in eyes with short TBUT with those in normal eyes. RESULTS: No
      significant differences in the MTF cutoff frequency, Strehl ratio, or OSI were
      detected over a 10-second period in normal eyes. These variables also became
      significantly degraded even over a 5-second period in eyes with short TBUT
      (p<0.01). We found significant differences in these variables at 5 and 10 seconds
      (p<0.05), but none immediately after the blink between normal and short TBUT
      eyes. CONCLUSIONS: Optical quality including intraocular scattering deteriorated
      significantly with time in eyes with short TBUT, whereas we found significant
      differences over a 10-second period in normal eyes. Eyes with short TBUT showed
      greater deterioration in optical quality after the blink than normal eyes. The
      longitudinal assessment of optical quality may be effective in distinguishing
      eyes with short TBUT from normal eyes.

PMID- 24324788
TI  - Incidence trends of urinary bladder and kidney cancers in urban Shanghai, 1973
      2005.
AB  - OBJECTIVES: We examined the incidence trends of bladder and kidney cancers using
      a population-based cancer registration data. METHODS: Age-standardized incidence
      rates were analyzed using data from the Shanghai Cancer Registry during 1973 to
      2005. Annual percentage changes and 95% confidence intervals were calculated to
      evaluate the incidence changes. Age-period-cohort analysis was further
      implemented to assess the contributions of age, period and cohort effects to the
      trends using the intrinsic estimator method. RESULTS: In total, 12,676 bladder
      and 5,811 kidney cancer patients were registered in urban Shanghai. The age
      standardized rates of bladder cancer in males increased from 6.39 to 7.66 per
      100,000, or 0.62% per year, whereas the rates in females increased from 1.95 to
      2.09 per 100,000, or 0.33% per year. For kidney cancer, the age-standardized
      rates in males increased from 1.20 to 5.64 per 100,000, or 6.98% per year.
      Similarly in females, the rates increased from 0.85 to 3.33 per 100,000, or 5.93%
      per year. Age-period-cohort analysis showed increasing curves of age and period
      effects but generally decreasing cohort effects for bladder and kidney cancers.
      CONCLUSIONS: Our results show increasing incidence trends of bladder and kidney
      cancers in Chinese men and women, especially for kidney cancer.

PMID- 24324789
TI  - Prevalence and associated factors for pterygium in rural agrarian central India.
      The central India eye and medical study.
AB  - PURPOSE: To evaluate the prevalence of pterygia and associated factors in a rural
      population in a mostly undeveloped agrarian region. METHODS: The Central India
      Eye and Medical Study is a population-based study performed in a rural region of
      Central India. The study comprised 4711 subjects (aged 30+ years). A detailed
      ophthalmic and medical examination was performed. A pterygium was diagnosed
      during the slit lamp examination and confirmed on corneal photographs. It was
      defined as a fleshy fibrovascular growth, crossing the limbus and typically seen
      on the nasal, and sometimes temporal, conjunctiva. RESULTS: A pterygium was
      detected in 798 eyes (prevalence rate: 8.47 +/- 0.29%) of 608 (12.91 +/- 0.49%)
      subjects. Bilateral pterygia were present in 190 subjects (4.0% of study
      population). Pterygia prevalence increased from 6.7 +/- 0.8% in the age group 30
      39 years, to 13.5 +/- 1.2% in the age group 50-59 years, to 25.3 +/- 2.1% in the
      age group 70-79 years. Prevalence of pterygia was associated with older age
      (P<0.001; regression coefficient B: 0.02; odds ratio (OR): 1.02; 95%CI: 1.01,
      1.03), male gender (P<0.001;B:-0.73;OR: .48;95%CI:0.39,0.61), lower level of
      education (P<0.001;B:-0.30;OR:0.74;95%CI:0.69,0.80), lower body height
      (P=0.001;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive
      error (P<0.001;B:0.23;OR:1.26;95%CI:1.18,1.34). If the education level was
      dropped, the number of hours spent with vigorous activity outdoors
      (P=0.001;B:0.001;OR:1.001;95%CI:1.000,1.0001) was significantly associated with
      the prevalence of pterygia, in addition to older age
      (P<0.001;B:0.03;OR:1.03;95%CI:1.03,1.04), male gender (P<0.001;B:
      0.49;OR:0.62;95%CI:0.49,0.77), lower body height (P=0.005;B:
      0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error
      (P<0.001;B:0.23;OR:1.25;95%CI:1.18,1.34). CONCLUSIONS: Pterygium prevalence in
      rural Central India is about 13% among adult Indians aged 30+ years. Older age,
      male gender, lower educational level, lower body height and more time spent
      outdoors with vigorous work were associated factors. Since the living conditions
      in the study location were mostly untouched by modern developments, the results
      may show the prevalence and associations of pterygia without major medical or
      technologic influences.

PMID- 24324790
TI  - Differential responsiveness of cortical microtubule orientation to suppression of
      cell expansion among the developmental zones of Arabidopsis thaliana root apex.
AB  - Tauhe bidirectional relationship between cortical microtubule orientation and
      cell wall structure has been extensively studied in elongating cells.
      Nevertheless, the possible interplay between microtubules and cell wall elements
      in meristematic cells still remains elusive. Herein, the impact of cellulose
      synthesis inhibition and suppressed cell elongation on cortical microtubule
      orientation was assessed throughout the developmental zones of Arabidopsis
      thaliana root apex by whole-mount tubulin immunolabeling and confocal microscopy.
      Apart from the wild-type, thanatos and pom2-4 mutants of Cellulose SynthaseA3 and
      Cellulose Synthase Interacting1, respectively, were studied. Pharmacological and
      mechanical approaches inhibiting cell expansion were also applied. Cortical
      microtubules of untreated wild-type roots were predominantly transverse in the
      meristematic, transition and elongation root zones. Cellulose-deficient mutants,
      chemical inhibition of cell expansion, or growth in soil resulted in microtubule
      reorientation in the elongation zone, wherein cell length was significantly
      decreased. Combinatorial genetic and chemical suppression of cell expansion
      extended microtubule reorientation to the transition zone. According to the
      results, transverse cortical microtubule orientation is established in the
      meristematic root zone, persisting upon inhibition of cell expansion. Microtubule
      reorientation in the elongation zone could be attributed to conditional
      suppression of cell elongation. The differential responsiveness of microtubule
      orientation to genetic and environmental cues is most likely associated with
      distinct biophysical traits of the cells among each developmental root zone. 

PMID- 24324791
TI  - Kruppel-like factor 6 rendered rat Schwann cell more sensitive to apoptosis via
      upregulating FAS expression.
AB  - Kruppel-like factor 6 (KLF6) is a tumor suppressor gene and play a role in the
      regulation of cell proliferation and apoptosis. After the peripheral nerve injury
      (PNI), the microenvironment created by surrounding Schwann cells (SCs) is a
      critical determinant of its regenerative potential. In this study, we examined
      the effects of KLF6 on SCs responses during PNI. Both KLF6 mRNA and protein
      expression levels were upregulated in the injured sciatic nerve, and
      immunofluorescence results showed that many KLF6-positive cells simultaneously
      expressed the SC markers S-100 and p75NTR. The apoptosis inducers TNFalpha and
      cisplatin upregulated KLF6 expression in primary cultured SCs and the SC line
      RSC96. Although KLF6 overexpression exacerbated cisplatin- and TNFalpha-induced
      apoptosis, expression levels of the apoptosis regulators Bcl2 and Bax were not
      significantly affected in either KLF6-overexpressing or KLF6-depleted RSC96
      cells. Realtime PCR arrays and qRT-PCR demonstrated that KLF6 overexpression
      upregulated four pro-apoptotic genes, FAS, TNF, TNFSF12, and PYCARD, and
      inhibited expression of the anti-apoptotic IL10 gene expression. Further analysis
      revealed that FAS protein expression was positively correlated with KLF6
      expression in SCs. These data suggest that KLF6 upregulation may render SCs more
      vulnerable to apoptosis after injury via upregulating FAS expression. 

PMID- 24324792
TI  - Differentially expressed transcripts and dysregulated signaling pathways and
      networks in African American breast cancer.
AB  - African Americans (AAs) have higher mortality rate from breast cancer than that
      of Caucasian Americans (CAs) even when socioeconomic factors are accounted for.
      To better understand the driving biological factors of this health disparity, we
      performed a comprehensive differential gene expression analysis, including
      subtype- and stage-specific analysis, using the breast cancer data in the Cancer
      Genome Atlas (TCGA). In total, 674 unique genes and other transcripts were found
      differentially expressed between these two populations. The numbers of
      differentially expressed genes between AA and CA patients increased in each stage
      of tumor progression: there were 26 in stage I, 161 in stage II, and 223 in stage
      III. Resistin, a gene that is linked to obesity, insulin resistance, and breast
      cancer, was expressed more than four times higher in AA tumors. An
      uncharacterized, long, non-coding RNA, LOC90784, was down-regulated in AA tumors,
      and its expression was inversely related to cancer stage and was the lowest in
      triple negative AA breast tumors. Network analysis showed increased expression of
      a majority of components in p53 and BRCA1 subnetworks in AA breast tumor samples,
      and members of the aurora B and polo-like kinase signaling pathways were also
      highly expressed. Higher gene expression diversity was observed in more advanced
      stage breast tumors suggesting increased genomic instability during tumor
      progression. Amplified resistin expression may indicate insulin-resistant type II
      diabetes and obesity are associated with AA breast cancer. Expression of LOC90784
      may have a protective effect on breast cancer patients, and its loss,
      particularly in triple negative breast cancer, could be having detrimental
      effects. This work helps elucidate molecular mechanisms of breast cancer health
      disparity and identifies putative biomarkers and therapeutic targets such as
      resistin, and the aurora B and polo-like kinase signaling pathways for treating
      AA breast cancer patients. 

PMID- 24324793
TI  - Immunological and virological benefits resulted from short-course treatment
      during primary HIV infection: a meta-analysis.
AB  - OBJECTIVES: To assess the potential immunological and virological effects that
      result from short-course antiretroviral treatment during primary HIV infection
      (PHI). And to investigate whether treatment initiation time, treatment duration
      and follow-up time after treatment interruption would affect these post-treatment
      immunovirological outcomes. METHODS: We systematically searched PubMed, Cochrane
      Library (to September 2013) and retrieved conference abstracts for studies
      regarding effects of early treatment during PHI on CD4 count and viral load (VL).
      Using the method of calculating weighted mean differences with Stata11.0, we
      conducted meta-analyses on the effect of early treatment on CD4 count and VL.
      Then we performed subgroup analyses by follow-up time after treatment
      interruption, treatment initiation time and treatment duration. Baseline
      immunovirological characteristics were also analyzed to account for potential
      bias. RESULTS: Compared to the untreated arm, treatment during PHI not only
      increased CD4 count by 85.92 cells/MUl but also lowered viral load by 0.30 log
      copies/ml within one year after treatment interruption. However, the benefits
      declined gradually, reaching no significance 12-24 months after treatment
      interruption. Baseline immunovirological characteristics and sensitivity analyses
      of randomized controlled trials indicated that the benefits mentioned above were
      underestimated. Extending treatment duration beyond 12 months did not increase
      efficacy. CONCLUSIONS: Short-course treatment during PHI was associated with
      immunological and virological benefits which last for at least one year after
      treatment interruption. The conclusions from our study would help the decision
      making in the clinical management of PHI.

PMID- 24324794
TI  - Soil nematode responses to increases in nitrogen deposition and precipitation in
      a temperate forest.
AB  - The environmental changes arising from nitrogen (N) deposition and precipitation
      influence soil ecological processes in forest ecosystems. However, the
      corresponding effects of environmental changes on soil biota are poorly known.
      Soil nematodes are the important bioindicator of soil environmental change, and
      their responses play a key role in the feedbacks of terrestrial ecosystems to
      climate change. Therefore, to explore the responsive mechanisms of soil biota to
      N deposition and precipitation, soil nematode communities were studied after 3
      years of environmental changes by water and/or N addition in a temperate forest
      of Changbai Mountain, Northeast China. The results showed that water combined
      with N addition treatment decreased the total nematode abundance in the organic
      horizon (O), while the opposite trend was found in the mineral horizon (A).
      Significant reductions in the abundances of fungivores, plant-parasites and
      omnivores-predators were also found in the water combined with N addition
      treatment. The significant effect of water interacted with N on the total
      nematode abundance and trophic groups indicated that the impacts of N on soil
      nematode communities were mediated by water availability. The synergistic effect
      of precipitation and N deposition on soil nematode communities was stronger than
      each effect alone. Structural equation modeling suggested water and N additions
      had direct effects on soil nematode communities. The feedback of soil nematodes
      to water and nitrogen addition was highly sensitive and our results indicate that
      minimal variations in soil properties such as those caused by climate changes can
      lead to severe changes in soil nematode communities. 

PMID- 24324796
TI  - Both group 4 capsule and lipopolysaccharide O-antigen contribute to
      enteropathogenic Escherichia coli resistance to human alpha-defensin 5.
AB  - Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are food
      borne pathogens that colonize the small intestine and colon, respectively. To
      cause disease, these pathogens must overcome the action of different host
      antimicrobial peptides (AMPs) secreted into these distinct niches. We have shown
      previously that EHEC expresses high levels of the OmpT protease to inactivate the
      human cathelicidin LL-37, an AMP present in the colon. In this study, we
      investigate the mechanisms used by EPEC to resist human alpha-defensin 5 (HD-5),
      the most abundant AMP in the small intestine. Quantitative PCR was used to
      measure transcript levels of various EPEC surface structures. High transcript
      levels of gfcA, a gene required for group 4 capsule (G4C) production, were
      observed in EPEC, but not in EHEC. The unencapsulated EPEC ?gfcA and EHEC wild
      type strains were more susceptible to HD-5 than EPEC wild-type. Since the G4C is
      composed of the same sugar repeats as the lipopolysaccharide O-antigen, an 
      antigen ligase (waaL) deletion mutant was generated in EPEC to assess its role in
      HD-5 resistance. The ?waaL EPEC strain was more susceptible to HD-5 than both the
      wild-type and ?gfcA strains. The ?gfcA?waaL EPEC strain was not significantly
      more susceptible to HD-5 than the ?waaL strain, suggesting that the absence of 
      antigen influences G4C formation. To determine whether the G4C and -antigen
      interact with HD-5, total polysaccharide was purified from wild-type EPEC and
      added to the ?gfcA?waaL strain in the presence of HD-5. The addition of exogenous
      polysaccharide protected the susceptible strain against HD-5 killing in a dose
      dependent manner, suggesting that HD-5 binds to the polysaccharides present on
      the surface of EPEC. Altogether, these findings indicate that EPEC relies on both
      the G4C and the -antigen to resist the bactericidal activity of HD-5. 

PMID- 24324795
TI  - Molecular strategies of the Caenorhabditis elegans dauer larva to survive extreme
      desiccation.
AB  - Massive water loss is a serious challenge for terrestrial animals, which usually
      has fatal consequences. However, some organisms have developed means to survive
      this stress by entering an ametabolic state called anhydrobiosis. The molecular
      and cellular mechanisms underlying this phenomenon are poorly understood. We
      recently showed that Caenorhabditis elegans dauer larva, an arrested stage
      specialized for survival in adverse conditions, is resistant to severe
      desiccation. However, this requires a preconditioning step at a mild desiccative
      environment to prepare the organism for harsher desiccation conditions. A systems
      approach was used to identify factors that are activated during this
      preconditioning. Using microarray analysis, proteomics, and bioinformatics,
      genes, proteins, and biochemical pathways that are upregulated during this
      process were identified. These pathways were validated via reverse genetics by
      testing the desiccation tolerances of mutants. These data show that the
      desiccation response is activated by hygrosensation (sensing the desiccative
      environment) via head neurons. This leads to elimination of reactive oxygen
      species and xenobiotics, expression of heat shock and intrinsically disordered
      proteins, polyamine utilization, and induction of fatty acid desaturation
      pathway. Remarkably, this response is specific and involves a small number of
      functional pathways, which represent the generic toolkit for anhydrobiosis in
      plants and animals. 

PMID- 24324797
TI  - 20-Hydroxyeicosatetraenoic acid contributes to the inhibition of K+ channel
      activity and vasoconstrictor response to angiotensin II in rat renal
      microvessels.
AB  - The present study examined whether 20-hydroxyeicosatetraenoic acid (HETE)
      contributes to the vasoconstrictor effect of angiotensin II (ANG II) in renal
      microvessels by preventing activation of the large conductance Ca(2+)-activated
      K(+) channel (KCa) in vascular smooth muscle (VSM) cells. ANG II increased the
      production of 20-HETE in rat renal microvessels. This response was attenuated by
      the 20-HETE synthesis inhibitors, 17-ODYA and HET0016, a phospholipase A2
      inhibitor AACOF3, and the AT1 receptor blocker, Losartan, but not by the AT2
      receptor blocker, PD123319. ANG II (10(-11) to 10(-6) M) dose-dependently
      decreased the diameter of renal microvessels by 41 +/- 5%. This effect was
      blocked by 17-ODYA. ANG II (10(-7) M) did not alter KCa channel activity recorded
      from cell-attached patches on renal VSM cells under control conditions. However,
      it did reduce the NPo of the KCa channel by 93.4 +/- 3.1% after the channels were
      activated by increasing intracellular calcium levels with ionomycin. The
      inhibitory effect of ANG II on KCa channel activity in the presence of ionomycin
      was attenuated by 17-ODYA, AACOF3, and the phospholipase C (PLC) inhibitor U
      73122. ANG II induced a peak followed by a steady-state increase in intracellular
      calcium concentration in renal VSM cells. 17-ODYA (10(-5) M) had no effect on the
      peak response, but it blocked the steady-state increase. These results indicate
      that ANG II stimulates the formation of 20-HETE in rat renal microvessels via the
      AT1 receptor activation and that 20-HETE contributes to the vasoconstrictor
      response to ANG II by blocking activation of KCa channel and facilitating calcium
      entry. 

PMID- 24324799
TI  - Influenza-like illness surveillance on Twitter through automated learning of
      naive language.
AB  - Twitter has the potential to be a timely and cost-effective source of data for
      syndromic surveillance. When speaking of an illness, Twitter users often report a
      combination of symptoms, rather than a suspected or final diagnosis, using naive,
      everyday language. We developed a minimally trained algorithm that exploits the
      abundance of health-related web pages to identify all jargon expressions related
      to a specific technical term. We then translated an influenza case definition
      into a Boolean query, each symptom being described by a technical term and all
      related jargon expressions, as identified by the algorithm. Subsequently, we
      monitored all tweets that reported a combination of symptoms satisfying the case
      definition query. In order to geolocalize messages, we defined 3 localization
      strategies based on codes associated with each tweet. We found a high correlation
      coefficient between the trend of our influenza-positive tweets and ILI trends
      identified by US traditional surveillance systems. 

PMID- 24324798
TI  - Structural and functional studies of a phosphatidic acid-binding antifungal plant
      defensin MtDef4: identification of an RGFRRR motif governing fungal cell entry.
AB  - MtDef4 is a 47-amino acid cysteine-rich evolutionary conserved defensin from a
      model legume Medicago truncatula. It is an apoplast-localized plant defense
      protein that inhibits the growth of the ascomycetous fungal pathogen Fusarium
      graminearum in vitro at micromolar concentrations. Little is known about the
      mechanisms by which MtDef4 mediates its antifungal activity. In this study, we
      show that MtDef4 rapidly permeabilizes fungal plasma membrane and is internalized
      by the fungal cells where it accumulates in the cytoplasm. Furthermore, analysis
      of the structure of MtDef4 reveals the presence of a positively charged gamma
      core motif composed of beta2 and beta3 strands connected by a positively charged
      RGFRRR loop. Replacement of the RGFRRR sequence with AAAARR or RGFRAA abolishes
      the ability of MtDef4 to enter fungal cells, suggesting that the RGFRRR loop is a
      translocation signal required for the internalization of the protein. MtDef4
      binds to phosphatidic acid (PA), a precursor for the biosynthesis of membrane
      phospholipids and a signaling lipid known to recruit cytosolic proteins to
      membranes. Amino acid substitutions in the RGFRRR sequence which abolish the
      ability of MtDef4 to enter fungal cells also impair its ability to bind PA. These
      findings suggest that MtDef4 is a novel antifungal plant defensin capable of
      entering into fungal cells and affecting intracellular targets and that these
      processes are mediated by the highly conserved cationic RGFRRR loop via its
      interaction with PA. 

PMID- 24324800
TI  - Impact of perinatal systemic hypoxic-ischemic injury on the brain of male
      offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in
      early preterm newborns.
AB  - In this study, we attempted to design a model using Sprague-Dawley rats to better
      reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early
      preterm newborns. On day 21 of gestation, the uterus of pregnant rats were
      exposed and the blood supply to the fetuses of neonatal HIE groups were
      thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses
      were moved from the uterus and manually stimulated to initiate breathing in an
      incubator at 37  degrees C for 1 hr in air. We showed that survival rates of
      offspring rats were decreased with longer hypoxic time. TUNEL staining showed
      that apoptotic cells were significant increased in the brains of offspring rats
      from the 10 min and 15 min HIE groups as compared to the offspring rats in the
      control group at postnatal day (PND) 1, but there was no statistical difference
      between the offspring rats in the 5 min HIE and control groups. The perinatal
      hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3
      protein levels in the offspring rats from all HIE groups at PND 1. Platform
      crossing times and the percentage of the time spent in the target quadrant of
      Morris Water Maze test were significantly reduced in the offspring rats of all
      HIE groups at PND 30, which were associated with decreased brain-derived
      neurotrophic factor levels and neuronal cells in the hippocampus of offspring
      rats at PND 35. These data demonstrated that perinatal ischemic injury led to the
      death of neuronal cells and long-lasting impairment of memory. This model
      reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be
      appropriate for investigating therapeutic interventions. 

PMID- 24324801
TI  - Chronic increase of urea leads to carbamylated proteins accumulation in tissues
      in a mouse model of CKD.
AB  - Carbamylation is a general process involved in protein molecular ageing due to
      the nonenzymatic binding of isocyanic acid, mainly generated by urea
      dissociation, to free amino groups. In vitro experiments and clinical studies
      have suggested the potential involvement of carbamylated proteins (CPs) in
      chronic kidney disease (CKD) complications like atherosclerosis, but their
      metabolic fate in vivo is still unknown. To address this issue, we evaluated
      protein carbamylation in the plasma and tissues of control and 75% nephrectomised
      C57BL/6J mice by LC-MS/MS assay of homocitrulline, the major carbamylation
      derived product (CDP). A basal level of carbamylation was evidenced under all
      conditions, showing that carbamylation is a physiological process of protein
      modification in vivo. CP plasma concentrations increased in nephrectomized vs.
      control mice over the 20 weeks of the experiment (e.g. 335 +/- 43 vs. 167 +/- 19
      MUmol homocitrulline/mol lysine (p<0.001) 20 weeks after nephrectomy).
      Simultaneously, CP content increased roughly by two-fold in all tissues
      throughout the experiment. The progressive accumulation of CPs was specifically
      noted in long-lived extracellular matrix proteins, especially collagen (e.g. 1264
      +/- 123 vs. 726 +/- 99 MUmol homocitrulline/mol lysine (p<0.01) in the skin of
      nephrectomized vs. control mice after 20 weeks of evolution). These results show
      that chronic increase of urea, as seen in CKD, increases the carbamylation rate
      of plasma and tissue proteins. These results may be considered in the perspective
      of the deleterious effects of CPs demonstrated in vitro and of the correlation
      evidenced recently between plasma CPs and cardiovascular risk or mortality in CKD
      patients.

PMID- 24324802
TI  - L1 cell adhesion molecule as a potential therapeutic target in murine models of
      endometriosis using a monoclonal antibody approach.
AB  - BACKGROUND/AIMS: The neural cell adhesion molecule L1CAM is a transmembrane
      glycoprotein abnormally expressed in tumors and previously associated with cell
      proliferation, adhesion and invasion, as well as neurite outgrowth in
      endometriosis. Being an attractive target molecule for antibody-based therapy,
      the present study assessed the ability of the monoclonal anti-L1 antibody (anti
      L1 mAb) to impair the development of endometriotic lesions in vivo and
      endometriosis-associated nerve fiber growth. METHODS AND RESULTS: Endometriosis
      was experimentally induced in sexually mature B6C3F1 (n=34) and CD-1 nude (n=21)
      mice by autologous and heterologous transplantation, respectively, of endometrial
      fragments into the peritoneal cavity. Transplantation was confirmed four weeks
      post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively.
      Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype
      control antibody twice weekly, over a period of four weeks. Upon treatment
      completion, mice were sacrificed and endometrial implants were excised, measured
      and fixed. Endometriosis was histologically confirmed and L1CAM was detected by
      immunohistochemistry. Endometriotic lesion size was significantly reduced in anti
      L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control
      antibody (P<0.05). Accordingly, a decreased number of PCNA positive epithelial
      and stromal cells was detected in autologously and heterologously induced
      endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also
      presented a diminished number of intraperitoneal adhesions at implantation sites
      compared with controls. Furthermore, a double-blind counting of anti
      neurofilament L stained nerves revealed significantly reduced nerve density
      within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039). CONCLUSIONS:
      Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1
      nude mice and exerted a potent anti-neurogenic effect on induced endometriotic
      lesions in vivo. The findings of this preliminary study in mice provide a strong
      basis for further testing in in vivo models.

PMID- 24324803
TI  - Microarray and morphological analysis of early postnatal CRB2 mutant retinas on a
      pure C57BL/6J genetic background.
AB  - In humans, the Crumbs homologue-1 (CRB1) gene is mutated in progressive types of
      autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. The
      severity of the phenotype due to human CRB1 or mouse Crb1 mutations is dependent
      on the genetic background. Mice on C57BL/6J background with Crb1 mutations show
      late onset of retinal spotting phenotype or no phenotype. Recently, we showed
      that conditional deletion of mouse Crb2 in the retina results in early retinal
      disorganization leading to severe and progressive retinal degeneration with
      concomitant visual loss that mimics retinitis pigmentosa due to mutations in the
      CRB1 gene. Recent studies in the fruit fly and zebrafish suggest roles of the
      Crumbs (CRB) complex members in the regulation of cellular signalling pathways
      including the Notch1, mechanistic target of rapamycin complex 1 (mTORC1) and the
      Hippo pathway. Here, we demonstrate that mice backcrossed to C57BL/6J background
      with loss of CRB2 in the retina show a progressive disorganization and
      degeneration phenotype during late retinal development. We used microarray gene
      profiling to study the transcriptome of retinas lacking CRB2 during late retinal
      development. Unexpectedly, the retinas of newborn mice lacking CRB2 showed no
      changes in the transcriptome during retinal development. These findings suggest
      that loss of CRB2 in the developing retina results in retinal disorganization and
      subsequent degeneration without major changes in the transcriptome of the retina.
      These mice might be an interesting model to study the onset of retinal
      degeneration upon loss of CRB proteins. 

PMID- 24324804
TI  - Associations between maternal and infant morbidities and sRAGE within the first
      week of life in extremely preterm infants.
AB  - BACKGROUND: Soluble RAGE (sRAGE) has been associated with multiple inflammatory
      responses including maternal chorioamnionitis and preeclampsia. Analysis of
      umbilical cord blood levels have also indicated that sRAGE levels in the infant
      are affected by maternal inflammation. S100b is a ligand for RAGE and increases
      in circulating S100b levels are associated with poor neurological outcome in
      preterm infants. The objective of this study was to determine whether sRAGE or
      s100b levels in plasma samples from extremely preterm infants at the end of the
      first week of life were correlated with infant morbidities and whether sRAGE and
      s100b levels at this time point were still associated with maternal inflammation.
      METHODS: Plasma samples were collected from 130 preterm infants (<=28 weeks) at
      days of life 5, 6, or 7. sRAGE and s100b levels were measured by ELISA and data
      were analyzed by Pearson's correlation or Generalized Estimating Equations.
      RESULTS: sRAGE was negatively correlated with development of sepsis (p=0.024),
      the FiO2 requirement of the infant at the time of sampling (p=0.030), as well as
      maternal preeclampsia (p=0.046), and positively correlated with maternal
      chorioamnionitis (p=0.006). s100b levels were positively associated with maternal
      chorioamnionitis (p=0.039). No correlations were observed with other infant
      morbidities. CONCLUSION: These data indicate that sRAGE could potentially be a
      biomarker of early severe inflammatory responses in the preterm infant. However,
      more studies are needed to confirm the present findings.

PMID- 24324805
TI  - MCPIP1 deficiency in mice results in severe anemia related to autoimmune
      mechanisms.
AB  - Autoimmune gastritis is an organ-specific autoimmune disease of the stomach
      associated with pernicious anemia. The previous work from us and other groups
      identified MCPIP1 as an essential factor controlling inflammation and immune
      homeostasis. MCPIP1(-/-) developed severe anemia. However, the mechanisms
      underlying this phenotype remain unclear. In the present study, we found that
      MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune
      mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the
      erythropoiesis in MCPIP1(-/-) bone marrow erythroblasts was significantly
      attenuated due to iron and vitamin B12 (VB12) deficiency, which was mainly
      resulted from autoimmunity-associated gastritis and parietal cell loss.
      Consistently, exogenous supplement of iron and VB12 greatly improved the anemia
      phenotype of MCPIP1(-/-) mice. Finally, we have evidence suggesting that
      autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1(-/-) mice.
      Taken together, our study suggests that MCPIP1 deficiency in mice leads to the
      development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1(-/-) mice
      may be a good mouse model for investigating the pathogenesis of pernicious anemia
      and testing the efficacy of some potential drugs for treatment of this disease.

PMID- 24324806
TI  - IFN-gamma Ralpha is a key determinant of CD8+ T cell-mediated tumor elimination
      or tumor escape and relapse in FVB mouse.
AB  - During the past decade, the dual function of the immune system in tumor
      inhibition and tumor progression has become appreciated. We have previously
      reported that neu-specific T cells can induce rejection of neu positive mouse
      mammary carcinoma (MMC) and also facilitate tumor relapse by inducing neu antigen
      loss and epithelial to mesenchymal transition (EMT). Here, we sought to determine
      the mechanism by which CD8+ T cells either eliminate the tumor, or maintain tumor
      cells in a dormant state and eventually facilitate tumor relapse. We show that
      tumor cells that express high levels of IFN-gamma Ralpha are eliminated by CD8+ T
      cells. In contrast, tumor cells that express low levels of IFN-gamma Ralpha do
      not die but remain dormant and quiescent in the presence of IFN-gamma producing
      CD8+ T cells until they hide themselves from the adaptive immune system by losing
      the tumor antigen, neu. Relapsed tumor cells show CD44+CD24- phenotype with
      higher rates of tumorigenesis, in vivo. Acquisition of CD44+CD24- phenotype in
      relapsed tumors was not solely due to Darwinian selection. Our data suggest that
      tumor cells control the outcome of tumor immune surveillance through modulation
      of the expression of    IFN-gamma Ralpha. 

PMID- 24324807
TI  - Whole genome sequencing reveals complex evolution patterns of multidrug-resistant
      Mycobacterium tuberculosis Beijing strains in patients.
AB  - Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains
      represent a major threat for tuberculosis (TB) control. Treatment of MDR-TB
      patients is long and less effective, resulting in a significant number of
      treatment failures. The development of further resistances leads to extensively
      drug-resistant (XDR) variants. However, data on the individual reasons for
      treatment failure, e.g. an induced mutational burst, and on the evolution of
      bacteria in the patient are only sparsely available. To address this question, we
      investigated the intra-patient evolution of serial MTBC isolates obtained from
      three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR
      TB. Sequential isolates displayed identical IS6110 fingerprint patterns,
      suggesting the absence of exogenous re-infection. We utilized whole genome
      sequencing (WGS) to screen for variations in three isolates from Patient A and
      four isolates from Patient B and C, respectively. Acquired polymorphisms were
      subsequently validated in up to 15 serial isolates by Sanger sequencing. We
      determined eight (Patient A) and nine (Patient B) polymorphisms, which occurred
      in a stepwise manner during the course of the therapy and were linked to
      resistance or a potential compensatory mechanism. For both patients, our analysis
      revealed the long-term co-existence of clonal subpopulations that displayed
      different drug resistance allele combinations. Out of these, the most resistant
      clone was fixed in the population. In contrast, baseline and follow-up isolates
      of Patient C were distinguished each by eleven unique polymorphisms, indicating
      an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing.
      Our study demonstrates that intra-patient microevolution of MDR-MTBC strains
      under longitudinal treatment is more complex than previously anticipated.
      However, a mutator phenotype was not detected. The presence of different
      subpopulations might confound phenotypic and molecular drug resistance tests.
      Furthermore, high resolution WGS analysis is necessary to accurately detect
      exogenous re-infection as classical genotyping lacks discriminatory power in high
      incidence settings. 

PMID- 24324808
TI  - Glycosylation of immunoglobulin g: role of genetic and epigenetic influences.
AB  - OBJECTIVE: To determine the extent to which genetic and epigenetic factors
      contribute to variations in glycosylation of immunoglobulin G (IgG) in humans.
      METHODS: 76 N-glycan traits in circulating IgG were analyzed by UPLC in 220
      monozygotic and 310 dizygotic twin pairs from TwinsUK. A classical twin study
      design was used to derive the additive genetic, common and unique environmental
      components defining the variance in these traits. Epigenome-wide association
      analysis was performed using the Illumina 27k chip. RESULTS: 51 of the 76 glycan
      traits studied have an additive genetic component (heritability, h (2) ) >= 0.5.
      In contrast, 12 glycan traits had a low genetic contribution (h(2)<0.35). We then
      tested for association between methylation levels and glycan levels (P<2 x10(
      6)). Among glycan traits with low heritability probe cg08392591 maps to a CpG
      island 5' from the ANKRD11 gene, a p53 activator on chromosome 16. Probe
      cg26991199 maps to the SRSF10 gene involved in regulation of RNA splicing and
      particularly in regulation of splicing of mRNA precursors upon heat shock. Among
      those with high heritability we found cg13782134 (mapping to the NRN1L gene) and
      cg16029957 mapping near the QPCT gene to be array-wide significant. The
      proportion of array-wide epigenetic associations was significantly larger
      (P<0.005) among glycans with low heritability (42%) than in those with high
      heritability (6.2%). CONCLUSIONS: Glycome analyses might provide a useful
      integration of genetic and non-genetic factors to further our understanding of
      the role of glycosylation in both normal physiology and disease.

PMID- 24324809
TI  - Regulation of heat shock proteins 27 and 70, p-Akt/p-eNOS and MAPKs by Naringin
      Dampens myocardial injury and dysfunction in vivo after ischemia/reperfusion.
AB  - Naringin has antioxidant properties that could improve redox-sensitive myocardial
      ischemia reperfusion (IR) injury. This study was designed to investigate whether
      naringin restores the myocardial damage and dysfunction in vivo after IR and the
      mechanisms underlying its cardioprotective effects. Naringin (20-80 mg/kg/day,
      p.o.) or saline were administered to rats for 14 days and the myocardial IR
      injury was induced on 15(th) day by occluding the left anterior descending
      coronary artery for 45 min and subsequent reperfusion for 60 min. Post-IR rats
      exhibited pronounced cardiac dysfunction as evidenced by significantly decreased
      mean arterial pressure, heart rate, +LVdP/dt max (inotropic state), -LVdP/dt max
      (lusitropic state) and increased left ventricular end diastolic pressure as
      compared to sham group, which was improved by naringin. Further, on
      histopathological and ultrastructural assessments myocardium and myocytes
      appeared more normal in structure and the infarct size was reduced significantly
      in naringin 40 and 80 mg/kg/day group. This amelioration of post-IR-associated
      cardiac injury by naringin was accompanied by increased nitric oxide (NO)
      bioavailability, decreased NO inactivation to nitrotyrosine, amplified protein
      expressions of Hsp27, Hsp70, beta-catenin and increased p-eNOS/eNOS, p-Akt/Akt,
      and p-ERK/ERK ratio. In addition, IR-induced TNF-alpha/IKK-beta/NF-kappaB
      upregulation and JNK phosphorylation were significantly attenuated by naringin.
      Moreover, western blotting and immunohistochemistry analysis of apoptotic
      signaling pathway further established naringin cardioprotective potential as it
      upregulated Bcl-2 expression and downregulated Bax and Caspase-3 expression with
      reduced TUNEL positivity. Naringin also normalized the cardiac injury markers
      (lactate dehydrogenase and creatine kinase-MB), endogenous antioxidant activities
      (superoxide dismutase, reduced glutathione and glutathione peroxidase) and lipid
      peroxidation levels. Thus, naringin restored IR injury by preserving myocardial
      structural integrity and regulating Hsp27, Hsp70, p-eNOS/p-Akt/p-ERK signaling
      and inflammatory response. 

PMID- 24324810
TI  - Can RNA-Seq resolve the rapid radiation of advanced moths and butterflies
      (Hexapoda: Lepidoptera: Apoditrysia)? An exploratory study.
AB  - Recent molecular phylogenetic studies of the insect order Lepidoptera have
      robustly resolved family-level divergences within most superfamilies, and most
      divergences among the relatively species-poor early-arising superfamilies. In
      sharp contrast, relationships among the superfamilies of more advanced moths and
      butterflies that comprise the mega-diverse clade Apoditrysia (ca. 145,000 spp.)
      remain mostly poorly supported. This uncertainty, in turn, limits our ability to
      discern the origins, ages and evolutionary consequences of traits hypothesized to
      promote the spectacular diversification of Apoditrysia. Low support along the
      apoditrysian "backbone" probably reflects rapid diversification. If so, it may be
      feasible to strengthen resolution by radically increasing the gene sample, but
      case studies have been few. We explored the potential of next-generation
      sequencing to conclusively resolve apoditrysian relationships. We used
      transcriptome RNA-Seq to generate 1579 putatively orthologous gene sequences
      across a broad sample of 40 apoditrysians plus four outgroups, to which we added
      two taxa from previously published data. Phylogenetic analysis of a 46-taxon, 741
      gene matrix, resulting from a strict filter that eliminated ortholog groups
      containing any apparent paralogs, yielded dramatic overall increase in bootstrap
      support for deeper nodes within Apoditrysia as compared to results from previous
      and concurrent 19-gene analyses. High support was restricted mainly to the huge
      subclade Obtectomera broadly defined, in which 11 of 12 nodes subtending multiple
      superfamilies had bootstrap support of 100%. The strongly supported nodes showed
      little conflict with groupings from previous studies, and were little affected by
      changes in taxon sampling, suggesting that they reflect true signal rather than
      artifacts of massive gene sampling. In contrast, strong support was seen at only
      2 of 11 deeper nodes among the "lower", non-obtectomeran apoditrysians. These
      represent a much harder phylogenetic problem, for which one path to resolution
      might include further increase in gene sampling, together with improved orthology
      assignments. 

PMID- 24324811
TI  - Pseudomonas aeruginosa enhances production of a non-alginate exopolysaccharide
      during long-term colonization of the cystic fibrosis lung.
AB  - The gram-negative opportunistic pathogen Pseudomonas aeruginosa is the primary
      cause of chronic respiratory infections in individuals with the heritable disease
      cystic fibrosis (CF). These infections can last for decades, during which time P.
      aeruginosa has been proposed to acquire beneficial traits via adaptive evolution.
      Because CF lacks an animal model that can acquire chronic P. aeruginosa
      infections, identifying genes important for long-term in vivo fitness remains
      difficult. However, since clonal, chronological samples can be obtained from
      chronically infected individuals, traits undergoing adaptive evolution can be
      identified. Recently we identified 24 P. aeruginosa gene expression traits
      undergoing parallel evolution in vivo in multiple individuals, suggesting they
      are beneficial to the bacterium. The goal of this study was to determine if these
      genes impact P. aeruginosa phenotypes important for survival in the CF lung. By
      using a gain-of-function genetic screen, we found that 4 genes and 2 operons
      undergoing parallel evolution in vivo promote P. aeruginosa biofilm formation.
      These genes/operons promote biofilm formation by increasing levels of the non
      alginate exopolysaccharide Psl. One of these genes, phaF, enhances Psl production
      via a post-transcriptional mechanism, while the other 5 genes/operons do not act
      on either psl transcription or translation. Together, these data demonstrate that
      P. aeruginosa has evolved at least two pathways to over-produce a non-alginate
      exopolysaccharide during long-term colonization of the CF lung. More broadly,
      this approach allowed us to attribute a biological significance to genes with
      unknown function, demonstrating the power of using evolution as a guide for
      targeted genetic studies. 

PMID- 24324812
TI  - Nod2 activates NF-kB in CD4+ T cells but its expression is dispensable for T cell
      induced colitis.
AB  - Although the etiology of Crohn's disease (CD) remains elusive this disease is
      characterized by T cell activation that leads to chronic inflammation and mucosal
      damage. A potential role for maladaptation between the intestinal microbiota and
      the mucosal immune response is suggested by the fact that mutations in the
      pattern recognition receptor Nod2 are associated with higher risks for developing
      CD. Although Nod2 deletion in CD4(+) T cells has been shown to impair the
      induction of colitis in the murine T cell transfer model, the analysis of T cell
      intrinsic Nod2 function in T cell differentiation and T cell-mediated immunity is
      inconsistent between several studies. In addition, the role of T cell intrinsic
      Nod2 in regulatory T cell (Treg) development and function during colitis remain
      to be analyzed. In this study, we show that Nod2 expression is higher in
      activated/memory CD4(+) T cells and its expression was inducible after T cell
      receptor (TCR) ligation. Nod2 stimulation with muramyl dipeptide (MDP) led to a
      nuclear accumulation of c-Rel NF-kB subunit. Although functionally active in
      CD4(+) T cells, the deletion of Nod2 did not impair the induction and the
      prevention of colitis in the T cell transfer model. Moreover, Nod2 deletion did
      not affect the development of Foxp3(+) Treg cells in the spleen of recipient mice
      and Nod2 deficient CD4 T cells expressing the OVA specific transgenic TCR were
      able to differentiate in Foxp3(+) Treg cells after OVA feeding. In vitro, CD25(+)
      Nod2 deficient T cells suppressed T cell proliferation as well as wild type
      counter parts and T cell stimulation with MDP did not affect the proliferation
      and the cytokine secretion of T cells. In conclusion, our data indicate that Nod2
      is functional in murine CD4(+) T cells but its expression is dispensable for the
      T cell regulation of colitis. 

PMID- 24324813
TI  - Rapid emergence of novel GII.4 sub-lineages noroviruses associated with outbreaks
      in Huzhou, China, 2008-2012.
AB  - Infection caused by noroviruses (NoVs) is one of the most important causes of
      acute gastroenteritis in humans worldwide. To gain insight into the epidemiology
      of and genetic variation in NoV strains, stool samples collected from 18
      outbreaks of acute gastroenteritis in Huzhou, China, between January 2008 and
      December 2012 were analyzed. Samples were tested for NoVs by real-time RT-PCR.
      Partial sequences of the RNA- dependent RNA polymerase (RdRp) and capsid gene of
      the positive samples were amplified by RT-PCR, and the PCR products were
      sequenced and used for phylogenetic analysis. NoVs were found to be responsible
      of 88.8% of all nonbacterial acute gastroenteritis outbreaks in Huzhou over the
      last 5 years. Genogroup II outbreaks largely predominated and represented 93% of
      all outbreaks. A variety of genotypes were found among genogroups I and II,
      including GI.4, GI.8, GII.4, and GII.b. Moreover, phylogenetic analyses
      identified two recombinant genotypes (polymerase/capsid): GI.2/GI.6 and
      GII.e/GII.4 2012 Sydney. GII.4 was predominant and involved in 8/10 typed
      outbreaks. During the study period, GII.4 NoV variants 2006b, New Orleans 2009,
      and Sydney 2012 were identified. This is the first report of the detection of
      GII.4 New Orleans 2009 variant, GII.e/GII.4 Sydney 2012 recombinant in outbreaks
      of acute gastroenteritis in China. 

PMID- 24324814
TI  - Multi-infections of feminizing Wolbachia strains in natural populations of the
      terrestrial isopod Armadillidium vulgare.
AB  - Maternally inherited Wolbachia (alpha-Proteobacteria) are widespread parasitic
      reproductive manipulators. A growing number of studies have described the
      presence of different Wolbachia strains within a same host. To date, no naturally
      occurring multiple infections have been recorded in terrestrial isopods. This is
      true for Armadillidium vulgare which is known to harbor non simultaneously three
      Wolbachia strains. Traditionally, such Wolbachia are detected by PCR
      amplification of the wsp gene and strains are characterized by sequencing. The
      presence of nucleotide deletions or insertions within the wsp gene, among these
      three different strains, provides the opportunity to test a novel genotyping
      method. Herein, we designed a new primer pair able to amplify products whose
      lengths are specific to each Wolbachia strain so as to detect the presence of
      multi-infections in A. vulgare. Experimental injections of Wolbachia strains in
      Wolbachia-free females were used to validate the methodology. We re-investigated,
      using this novel method, the infection status of 40 females sampled in 2003 and
      previously described as mono-infected based on the classical sequencing method.
      Among these females, 29 were identified as bi-infected. It is the first time that
      naturally occurring multiple infections of Wolbachia are detected within an
      individual A. vulgare host. Additionally, we resampled 6 of these populations in
      2010 to check the infection status of females.

PMID- 24324816
TI  - The impact of androgen receptor expression on breast cancer survival: a
      retrospective study and meta-analysis.
AB  - Recent studies have highlighted the role of androgen receptor (AR) as a
      prognostic biomarker of breast cancer. However, its predictive role in disease
      free survival (DFS) and overall survival (OS) still remains inconclusive. The
      present study aimed to retrospectively investigate the association between AR and
      survival outcomes in breast cancer and also identify this association by a meta
      analysis of published researches. Clinical data from 109 patients with breast
      cancer, who underwent surgery at Ruijin Hospital, Shanghai, were retrospectively
      analyzed for immunohistochemical AR expression measured by tissue microarray. For
      meta-analysis, articles available in Pubmed on the relationship between AR and
      breast cancer outcomes were included. Data obtained from both were combined and
      analyzed. Women with AR positive tumors in the retrospective study had a
      significantly better DFS (HR 0.24, 95% CI 0.07-0.88) and OS (HR 0.19, 95% CI 0.04
      0.85) than women with AR negative ones. Meta-analysis showed that AR expression
      in breast tumors was an indicator of better DFS (HR 0.52, 95% CI 0.43-0.64). In
      subgroup analysis, AR could predict DFS outcome in estrogen receptor (ER)
      positive (HR 0.45, 95% CI 0.34-0.59), ER negative (HR 0.42, 95% CI 0.26-0.67),
      and triple negative breast cancer (HR 0.40, 95% CI 0.23-0.69). Moreover, in ER
      positive breast cancer patients, the expression of AR could predict better OS (HR
      0.39, 95% CI 0.19-0.82). The present analysis indicated that AR expression was
      associated with lower risk of recurrence in patients with all breast cancer types
      and better OS in cases with ER positive. 

PMID- 24324817
TI  - Investigation of preparation and mechanisms of a dispersed particle gel formed
      from a polymer gel at room temperature.
AB  - A dispersed particle gel (DPG) was successfully prepared from a polymer gel at
      room temperature. The polymer gel system, morphology, viscosity changes, size
      distribution, and zeta potential of DPG particles were investigated. The results
      showed that zirconium gel systems with different strengths can be cross-linked
      within 2.5 h at low temperature. Scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), and atomic force microscopy (AFM) results showed that
      the particles were polygonal particles with nano-size distribution. According to
      the viscosity changes, the whole preparation process can be divided into two
      major stages: the bulk gel cross-linking reaction period and the DPG particle
      preparation period. A polymer gel with a 3-dimensional network was formed in the
      bulk gel cross-linking reaction period whereas shearing force and frictional
      force were the main driving forces for the preparation of DPG particles, and thus
      affected the morphology of DPG particles. High shearing force and frictional
      force reduced the particle size distribution, and then decreased the zeta
      potential (absolute value). The whole preparation process could be completed
      within 3 h at room temperature. It could be an efficient and energy-saving
      technology for preparation of DPG particles. 

PMID- 24324815
TI  - RNA-Seq transcriptome profiling of upland cotton (Gossypium hirsutum L.) root
      tissue under water-deficit stress.
AB  - An RNA-Seq experiment was performed using field grown well-watered and naturally
      rain fed cotton plants to identify differentially expressed transcripts under
      water-deficit stress. Our work constitutes the first application of the newly
      published diploid D5 Gossypium raimondii sequence in the study of tetraploid AD1
      upland cotton RNA-seq transcriptome analysis. A total of 1,530 transcripts were
      differentially expressed between well-watered and water-deficit stressed root
      tissues, in patterns that confirm the accuracy of this technique for future
      studies in cotton genomics. Additionally, putative sequence based genome
      localization of differentially expressed transcripts detected A2 genome specific
      gene expression under water-deficit stress. These data will facilitate efforts to
      understand the complex responses governing transcriptomic regulatory mechanisms
      and to identify candidate genes that may benefit applied plant breeding programs.

PMID- 24324818
TI  - In silico assigned resistance genes confer Bifidobacterium with partial
      resistance to aminoglycosides but not to beta-lactams.
AB  - Bifidobacteria have received significant attention due to their contribution to
      human gut health and the use of specific strains as probiotics. It is thus not
      surprising that there has also been significant interest with respect to their
      antibiotic resistance profile. Numerous culture-based studies have demonstrated
      that bifidobacteria are resistant to the majority of aminoglycosides, but are
      sensitive to beta-lactams. However, limited research exists with respect to the
      genetic basis for the resistance of bifidobacteria to aminoglycosides. Here we
      performed an in-depth in silico analysis of putative Bifidobacterium-encoded
      aminoglycoside resistance proteins and beta-lactamases and assess the
      contribution of these proteins to antibiotic resistance. The in silico-based
      screen detected putative aminoglycoside and beta-lactam resistance proteins
      across the Bifidobacterium genus. Laboratory-based investigations of a number of
      representative bifidobacteria strains confirmed that despite containing putative
      beta-lactamases, these strains were sensitive to beta-lactams. In contrast, all
      strains were resistant to the aminoglycosides tested. To assess the contribution
      of genes encoding putative aminoglycoside resistance proteins in Bifidobacterium
      sp. two genes, namely Bbr_0651 and Bbr_1586, were targeted for insertional
      inactivation in B. breve UCC2003. As compared to the wild-type, the UCC2003
      insertion mutant strains exhibited decreased resistance to gentamycin, kanamycin
      and streptomycin. This study highlights the associated risks of relying on the in
      silico assignment of gene function. Although several putative beta-lactam
      resistance proteins are located in bifidobacteria, their presence does not
      coincide with resistance to these antibiotics. In contrast however, this approach
      has resulted in the identification of two loci that contribute to the
      aminoglycoside resistance of B. breve UCC2003 and, potentially, many other
      bifidobacteria. 

PMID- 24324819
TI  - Selective vulnerability of spinal and cortical motor neuron subpopulations in
      delta7 SMA mice.
AB  - Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular
      atrophy (SMA), the most common inherited cause of infant mortality. Even though
      the SMA phenotype is traditionally considered as related to spinal motor neuron
      loss, it remains debated whether the specific targeting of motor neurons could
      represent the best therapeutic option for the disease. We here investigated,
      using stereological quantification methods, the spinal cord and cerebral motor
      cortex of ?7 SMA mice during development, to verify extent and selectivity of
      motor neuron loss. We found progressive post-natal loss of spinal motor neurons,
      already at pre-symptomatic stages, and a higher vulnerability of motor neurons
      innervating proximal and axial muscles. Larger motor neurons decreased in the
      course of disease, either for selective loss or specific developmental
      impairment. We also found a selective reduction of layer V pyramidal neurons
      associated with layer V gliosis in the cerebral motor cortex. Our data indicate
      that in the ?7 SMA model SMN loss is critical for the spinal cord, particularly
      for specific motor neuron pools. Neuronal loss, however, is not selective for
      lower motor neurons. These data further suggest that SMA pathogenesis is likely
      more complex than previously anticipated. The better knowledge of SMA models
      might be instrumental in shaping better therapeutic options for affected
      patients. 

PMID- 24324820
TI  - Behavioural lateralization in Budgerigars varies with the task and the
      individual.
AB  - Handedness/footedness and side biases are a well-known phenomenon in many
      animals, including humans. However, these so-called biases have mostly been
      studied at the population level--individual biases have received less attention,
      especially with regard to consistency over different tasks. Here we investigate
      behavioral lateralization in 12 male Budgerigars, Melopsittacus undulatus, a
      social parrot inhabiting the Australian bushlands. We performed 5 types of
      experiments to investigate lateralization, in tasks that involved climbing onto a
      perch, or landing on perches arranged in various configurations. The birds
      displayed highly significant, individually varying biases. The bias displayed by
      any particular individual varied with the task, in strength as well as polarity.
      Analysis of the data revealed that the preferred foot used for climbing did not
      coincide with the foot that was used while landing. Thus, landing choices are
      probably not determined by foot bias. Furthermore, these individual preferences
      were overridden completely when a bird had to perform a task simultaneously with
      another bird.

PMID- 24324821
TI  - Adherence to physician recommendations for surveillance in opportunistic
      colorectal cancer screening: the necessity of organized surveillance.
AB  - BACKGROUND: Limited evidence exists on the utilization of surveillance
      colonoscopy in colorectal cancer (CRC) screening programs. We assessed adherence
      to physician recommendations for surveillance in opportunistic CRC screening in
      Germany. METHODS: A follow-up study of screening colonoscopy participants in 2007
      2009 in Saarland, Germany, was conducted using health insurance claims data.
      Utilization of additional colonoscopies through to 2011 was ascertained.
      Adherence to surveillance intervals of 3, 6, 12 and 36 months, defined as having
      had colonoscopy at 2.5 to 4, 5 to 8, 10.5 to 16 and 33 to 48 months, respectively
      (i.e., tolerating a delay of 33% of each interval) was assessed. Potential
      predictors of non-adherence were investigated using logistic regression analysis.
      RESULTS: A total of 20,058 screening colonoscopy participants were included in
      the study. Of those with recommended surveillance intervals of 3, 6, 12 and 36
      months, 46.5% (95%-confidence interval [CI]: 37.3-55.7%), 38.5% (95%-CI: 29.6
      47.3%), 25.4% (95%-CI: 21.2-29.6%) and 28.0% (95%-CI: 25.5-30.5%), respectively,
      had a subsequent colonoscopy within the specified margins. Old age, longer
      recommended surveillance interval, not having had polypectomy at screening and
      negative colonoscopy were statistically significant predictors of non-adherence.
      CONCLUSION: This study suggests frequent non-adherence to physician
      recommendations for surveillance colonoscopy in community practice. Increased
      efforts to improve adherence, including introduction of more elements of an
      organized screening program, seem necessary to assure a high-quality CRC
      screening process.

PMID- 24324822
TI  - Measurement of cerebral white matter perfusion using pseudocontinuous arterial
      spin labeling 3T magnetic resonance imaging--an experimental and theoretical
      investigation of feasibility.
AB  - PURPOSE: This study was aimed to experimentally and numerically investigate the
      feasibility of measuring cerebral white matter perfusion using pseudocontinuous
      arterial spin labeling (PCASL) 3T magnetic resonance imaging (MRI) at a
      relatively fine resolution to mitigate partial volume effect from gray matter.
      MATERIALS AND METHODS: The Institutional Research Ethics Committee approved this
      study. On a clinical 3T MR system, ten healthy volunteers (5 females, 5 males,
      age = 28 +/- 3 years) were scanned after providing written informed consent.
      PCASL imaging was performed with varied combinations of labeling duration (tau =
      1000, 1500, 2000, and 2500 ms) and post-labeling delay (PLD = 1000, 1400, 1800,
      and 2200 ms), at a spatial resolution (1.56 x 1.56 x 5 mm(3)) finer than commonly
      used (3.5 x 3.5 mm(2), 5-8 mm in thickness). Computer simulations were performed
      to calculate the achievable perfusion-weighted signal-to-noise ratio at varied
      tau, PLD, and transit delay. RESULTS: Based on experimental and numerical data,
      the optimal tau and PLD were found to be 2000 ms and 1500-1800 ms, respectively,
      yielding adequate SNR (~2) to support perfusion measurement in the majority
      (~60%) of white matter. The measurement variability was about 9% in a one-week
      interval. The measured white matter perfusion and perfusion ratio of gray matter
      to white matter were 15.8-27.5 ml/100ml/min and 1.8-4.0, respectively, depending
      on spatial resolution as well as the amount of deep white matter included.
      CONCLUSION: PCASL 3T MRI is able to measure perfusion in the majority of cerebral
      white matter at an adequate signal-to-noise ratio by using appropriate tagging
      duration and post-labeling delay. Although pixel-wise comparison may not be
      possible, region-of-interest based flow quantification is feasible.

PMID- 24324823
TI  - Sustained photosynthetic performance of Coffea spp. under long-term enhanced
      [CO2].
AB  - Coffee is one of the world's most traded agricultural products. Modeling studies
      have predicted that climate change will have a strong impact on the suitability
      of current cultivation areas, but these studies have not anticipated possible
      mitigating effects of the elevated atmospheric [CO2] because no information
      exists for the coffee plant. Potted plants from two genotypes of Coffea arabica
      and one of C. canephora were grown under controlled conditions of irradiance (800
      MUmol m(-2) s(-1)), RH (75%) and 380 or 700 MUL CO2 L(-1) for 1 year, without
      water, nutrient or root development restrictions. In all genotypes, the high
      [CO2] treatment promoted opposite trends for stomatal density and size, which
      decreased and increased, respectively. Regardless of the genotype or the growth
      [CO2], the net rate of CO2 assimilation increased (34-49%) when measured at 700
      than at 380 MUL CO2 L(-1). This result, together with the almost unchanged
      stomatal conductance, led to an instantaneous water use efficiency increase. The
      results also showed a reinforcement of photosynthetic (and respiratory)
      components, namely thylakoid electron transport and the activities of RuBisCo,
      ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may
      have contributed to the enhancements in the maximum rates of electron transport,
      carboxylation and photosynthetic capacity under elevated [CO2], although these
      responses were genotype dependent. The photosystem II efficiency, energy driven
      to photochemical events, non-structural carbohydrates, photosynthetic pigment and
      membrane permeability did not respond to [CO2] supply. Some alterations in total
      fatty acid content and the unsaturation level of the chloroplast membranes were
      noted but, apparently, did not affect photosynthetic functioning. Despite some
      differences among the genotypes, no clear species-dependent responses to elevated
      [CO2] were observed. Overall, as no apparent sign of photosynthetic down
      regulation was found, our data suggest that Coffea spp. plants may successfully
      cope with high [CO2] under the present experimental conditions. 

PMID- 24324824
TI  - Folic acid protects against lipopolysaccharide-induced preterm delivery and
      intrauterine growth restriction through its anti-inflammatory effect in mice.
AB  - Increasing evidence demonstrates that maternal folic acid (FA) supplementation
      during pregnancy reduces the risk of neural tube defects, but whether FA prevents
      preterm delivery and intrauterine growth restriction (IUGR) remains obscure.
      Previous studies showed that maternal lipopolysaccharide (LPS) exposure induces
      preterm delivery, fetal death and IUGR in rodent animals. The aim of this study
      was to investigate the effects of FA on LPS-induced preterm delivery, fetal death
      and IUGR in mice. Some pregnant mice were orally administered with FA (0.6, 3 or
      15 mg/kg) 1 h before LPS injection. As expected, a high dose of LPS (300 MUg/kg,
      i.p.) on gestational day 15 (GD15) caused 100% of dams to deliver before GD18 and
      89.3% of fetuses dead. A low dose of LPS (75 MUg/kg, i.p.) daily from GD15 to
      GD17 resulted in IUGR. Interestingly, pretreatment with FA prevented LPS-induced
      preterm delivery and fetal death. In addition, FA significantly attenuated LPS
      induced IUGR. Further experiments showed that FA inhibited LPS-induced activation
      of nuclear factor kappa B (NF-kappaB) in mouse placentas. Moreover, FA suppressed
      LPS-induced NF-kappaB activation in human trophoblast cell line JEG-3.
      Correspondingly, FA significantly attenuated LPS-induced upregulation of
      cyclooxygenase (COX)-2 in mouse placentas. In addition, FA significantly reduced
      the levels of interleukin (IL)-6 and keratinocyte-derived cytokine (KC) in
      amniotic fluid of LPS-treated mice. Collectively, maternal FA supplementation
      during pregnancy protects against LPS-induced preterm delivery, fetal death and
      IUGR through its anti-inflammatory effects. 

PMID- 24324825
TI  - Proteomics analysis of alfalfa response to heat stress.
AB  - The proteome responses to heat stress have not been well understood. In this
      study, alfalfa (Medicago sativa L. cv. Huaiyin) seedlings were exposed to 25 
      degrees C (control) and 40  degrees C (heat stress) in growth chambers, and
      leaves were collected at 24, 48 and 72 h after treatment, respectively. The
      morphological, physiological and proteomic processes were negatively affected
      under heat stress. Proteins were extracted and separated by two-dimensional
      polyacrylamide gel electrophoresis (2-DE), and differentially expressed protein
      spots were identified by mass spectrometry (MS). Totally, 81 differentially
      expressed proteins were identified successfully by MALDI-TOF/TOF. These proteins
      were categorized into nine classes: including metabolism, energy, protein
      synthesis, protein destination/storage, transporters, intracellular traffic, cell
      structure, signal transduction and disease/defence. Five proteins were further
      analyzed for mRNA levels. The results of the proteomics analyses provide a better
      understanding of the molecular basis of heat-stress responses in alfalfa.

PMID- 24324826
TI  - Transcriptional heterogeneity of IgM+ cells in rainbow trout (Oncorhynchus
      mykiss) tissues.
AB  - TWO major classes of b lymphocytes have been described to date in rainbow trout:
      IgM(+) and IgT(+) cells. IgM(+) cells are mainly localized in the spleen,
      peripheral blood and kidney but are also found in other tissues. However,
      differences among IgM(+) cell populations attending to its location are poorly
      defined in fish. Thus, the aim of this work was to characterize the expression of
      different immune molecules such as chemokine receptors, Toll-like receptors
      (TLRs) and transcription factors on sorted IgM(+) lymphocytes from different
      rainbow trout tissues. IgM(+) populations from blood, spleen, kidney, gills,
      intestine and liver were isolated by cell sorting and the constitutive levels of
      transcription of these genes evaluated by real-time PCR. To further characterize
      B cells, we identified an MS4A sequence. In humans, the MS4A family includes
      several genes with immune functions, such as the B cell marker CD20 or FcRbeta.
      Subsequently, we have also evaluated the mRNA levels of this MS4A gene in the
      different IgM(+) populations. The relevant differences in transcriptional
      patterns observed for each of these IgM(+) populations analyzed, point to the
      presence of functionally different tissue-specific B cell populations in rainbow
      trout. The data shown provides a pattern of genes transcribed in IgM(+) B cells
      not previously revealed in teleost fish. Furthermore, the constitutive expression
      of all the TLR genes analyzed in IgM(+) cells suggests an important role for
      these cells in innate immunity.

PMID- 24324827
TI  - Serum albumin and body weight as biomarkers for the antemortem identification of
      bone and gastrointestinal disease in the common marmoset.
AB  - The increasing use of the common marmoset (Callithrix jacchus) in research makes
      it important to diagnose spontaneous disease that may confound experimental
      studies. Bone disease and gastrointestinal disease are two major causes of
      morbidity and mortality in captive marmosets, but currently no effective
      antemortem tests are available to identify affected animals prior to the terminal
      stage of disease. In this study we propose that bone disease and gastrointestinal
      disease are associated disease entities in marmosets and aim to establish the
      efficacy of several economical antemortem tests in identifying and predicting
      disease. Tissues from marmosets were examined to define affected animals and
      unaffected controls. Complete blood count, serum chemistry values, body weight,
      quantitative radiographs, and tissue-specific biochemical markers were evaluated
      as candidate biomarkers for disease. Bone and gastrointestinal disease were
      associated, with marmosets being over seven times more likely to have either
      concurrent bone and gastrointestinal disease or neither disease as opposed to
      lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL
      and body weight <325 g identified 100% of the marmosets affected with concurrent
      bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak
      body weight per day predicted which marmosets would develop disease prior to the
      terminal stage. Bone tissue-specific tests, such as quantitative analysis of
      radiographs and serum parathyroid hormone levels, were effective for
      distinguishing between marmosets with bone disease and those without. These
      results provide an avenue for making informed decisions regarding the removal of
      affected marmosets from studies in a timely manner, preserving the integrity of
      research results. 

PMID- 24324828
TI  - Mutation at intronic repeats of the ataxia-telangiectasia mutated (ATM) gene and
      ATM protein loss in primary gastric cancer with microsatellite instability.
AB  - Ataxia-telangiectasia mutated (ATM) is a Ser/Thr protein kinase that plays a
      critical role in DNA damage-induced signaling and initiation of cell cycle
      checkpoint signaling in response to DNA-damaging agents such as ionizing
      radiation. We have previously reported the ATM protein loss by
      immunohistochemistry (IHC) in 16% of human gastric cancer (GC) tissue. We
      hypothesized that ATM gene intron mutations targeted by microsatellite
      instability (MSI) cause ATM protein loss in a subset of GC. We studied
      mononucleotide mutations at the intron of ATM gene, ATM IHC and MSI in GC. Ten
      human gastric cancer cell lines were studied for the ATM gene mutation at
      introns, RT-PCR, direct sequencing, and immunohistochemistry. GC tissues of 839
      patients were analyzed for MSI and ATM IHC. Among them, 604 cases were analyzed
      for the ATM mutations at introns preceding exon 6, exon 10 and exon 20. Two human
      GC cell lines (SNU-1 and -638) showed ATM intron mutations, deletion in RT-PCR
      and direct sequencing, and ATM protein loss by IHC. The frequencies of ATM
      mutation, MSI, and ATM protein loss were 12.9% (78/604), 9.2% (81/882) and 15.2%
      (134/839), respectively. Analysis of associations among MSI, ATM gene mutation,
      and ATM protein loss revealed highly co-existing ATM gene alterations and MSI.
      ATM intron mutation and ATM protein loss were detected in 69.3% (52/75) and 53.3%
      (40/75) of MSI positive GC. MSI positivity and ATM protein loss were present in
      68.4% (52/76) and 48.7% (37/76) of GC with ATM intron mutation. ATM mutation and
      ATM protein loss had characteristics of old age, distal location of tumor, large
      tumor size, and histologic intestinal type. Our study might be interpreted as
      that ATM gene mutation at intron might be targeted by MSI and lead to ATM protein
      loss in a selected group of GC. 

PMID- 24324829
TI  - New host range for Hematodinium in southern Australia and novel tools for
      sensitive detection of parasitic dinoflagellates.
AB  - Hematodinium is a parasitic dinoflagellate and emerging pathogen of crustaceans.
      It preferably manifests in haemolymph of marine decapod crustaceans, killing a
      large variety of genera with significant impacts on fisheries worldwide. There
      is, however, evidence that some crustacean stocks harbor high prevalence, low
      intensity infections that may not result in widespread host mortality and are
      therefore hard to detect. The most widely used methods for detection of
      Hematodinium are conventional blood smears and polymerase chain reaction (PCR)
      against ribosomal RNAs. Blood smears demand a trained investigator, are labor
      intensive and not readily scalable for high-throughput sampling. PCRs only detect
      parasite DNA and can also suffer from false negatives and positives. In order to
      develop alternative detection tools for Hematodinium cells in decapod crustaceans
      we employed an immunological approach against a newly identified, abundant
      dinoflagellate-specific nuclear protein--Dinoflagellate/Viral NucleoProtein
      (DVNP). Both immunofluorescence assay (IFA) and Western blot methods against DVNP
      showed high sensitivity of detection. The Western blot detects Hematodinium
      parasites to levels of 25 parasites per milliliter of crustacean haemolymph, with
      the potential for sample pooling and screening of large samples. Using both PCR
      and these new tools, we have identified Hematodinium cells present in three new
      host crab taxa, at high prevalence but with no sign of pathogenesis. This extends
      the known range of Hematodinium to southern Australia.

PMID- 24324830
TI  - Morphology, chemistry and function of the postpharyngeal gland in the South
      American digger wasps Trachypus boharti and Trachypus elongatus.
AB  - Microbes pose severe threats to animals as competitors or pathogens and strongly
      affect the evolution of life history traits like parental care. Females of the
      European beewolf Philanthus triangulum, a solitary digger wasp, provision their
      offspring with paralyzed honeybees and embalm them with the secretion from large
      postpharyngeal glands (PPG) that contain mainly unsaturated hydrocarbons. This
      coating changes the physico-chemical properties of the prey surface, causes a
      reduction of water condensation and retards growth of mold fungi. Here we
      examined the closely related South American genus Trachypus, which shows a life
      history similar to Philanthus. We investigated whether Trachypus spp. also
      possess PPGs and embalm larval provisions. Using histological methods and 3D
      reconstructions we show that Trachypus boharti and T. elongatus possess PPGs that
      are similar to P. triangulum but somewhat smaller. The ultrastructure of the
      gland epithelium suggests that the gland content is at least partly sequestered
      from the hemolymph. Chemical analyses using gas chromatography / mass
      spectrometry revealed that both the cuticle and PPGs of Trachypus contain mainly
      unsaturated long-chain hydrocarbons. The gland of T. boharti additionally
      contains long-chain ketones. The hydrocarbons from the PPG of T. elongatus
      occurred on prey bees excavated from nests in the field but not on conspecific
      control bees. While the embalming only slightly elevated the amount of
      hydrocarbons on prey bees, the proportion of unsaturated hydrocarbons, which is
      crucial for the antifungal effect, was significantly increased. The Trachypus
      species under study possess PPGs that are very similar to the PPG of P.
      triangulum with regard to morphology, ultrastructure and chemistry. Moreover, we
      provide clear evidence that T. elongatus females embalm their prey, presumably as
      a means of prey preservation. The observed differences among Trachypus and
      Philanthus in gland size and prey embalming may have evolved in response to
      divergent ecological conditions. 

PMID- 24324831
TI  - The adverse effect of selective cyclooxygenase-2 inhibitor on random skin flap
      survival in rats.
AB  - BACKGROUND: Cyclooxygenase-2(COX-2) inhibitors provide desired analgesic effects
      after injury or surgery, but evidences suggested they also attenuate wound
      healing. The study is to investigate the effect of COX-2 inhibitor on random skin
      flap survival. METHODS: The McFarlane flap model was established in 40 rats and
      evaluated within two groups, each group gave the same volume of Parecoxib and
      saline injection for 7 days. The necrotic area of the flap was measured, the
      specimens of the flap were stained with haematoxylin-eosin(HE) for histologic
      analysis. Immunohistochemical staining was performed to analyse the level of VEGF
      and COX-2 . RESULTS: 7 days after operation, the flap necrotic area ratio in
      study group (66.65 +/- 2.81)% was significantly enlarged than that of the control
      group(48.81 +/- 2.33)%(P <0.01). Histological analysis demonstrated angiogenesis
      with mean vessel density per mm(2) being lower in study group (15.4 +/- 4.4) than
      in control group (27.2 +/- 4.1) (P <0.05). To evaluate the expression of COX-2
      and VEGF protein in the intermediate area II in the two groups by
      immunohistochemistry test .The expression of COX-2 in study group was (1022.45 +/
      153.1), and in control group was (2638.05 +/- 132.2) (P <0.01). The expression
      of VEGF in the study and control groups were (2779.45 +/- 472.0) vs (4938.05 +/-
      123.6)(P <0.01).In the COX-2 inhibitor group, the expressions of COX-2 and VEGF
      protein were remarkably down-regulated as compared with the control group.
      CONCLUSION: Selective COX-2 inhibitor had adverse effect on random skin flap
      survival. Suppression of neovascularization induced by low level of VEGF was
      supposed to be the biological mechanism.

PMID- 24324832
TI  - An amino acid deletion inSZT2 in a family with non-syndromic intellectual
      disability.
AB  - Autosomal recessive intellectual disability (ID) is characterized by extensive
      genetic heterogeneity. Recently, three mutations in SZT2 were reported in two
      unrelated children with unexplained infantile epileptic encephalopathy with
      severe ID. Here we report a European American family with three children having
      non-syndromic mild or moderate ID without seizures. Whole-exome sequencing of
      three affected siblings revealed a three base pair deletion (c.4202_4204delTTC)
      located in a 19 mb autozygous region on chromosome 1, leading to an amino acid
      deletion (p.Phe1401del) in SZT2. All three children were homozygous for the
      deletion and their parents were heterozygous as expected in autosomal recessive
      inheritance. SZT2 is highly expressed in neuronal tissues and regulates seizure
      threshold and neuronal excitation in mice. We conclude that the disruption of
      SZT2 with some residual function might lead to mild or moderate ID without
      seizures. 

PMID- 24324833
TI  - Characterisation of age-dependent beta cell dynamics in the male db/db mice.
AB  - AIM: To characterise changes in pancreatic beta cell mass during the development
      of diabetes in untreated male C57BLKS/J db/db mice. METHODS: Blood samples were
      collected from a total of 72 untreated male db/db mice aged 5, 6, 8, 10, 12, 14,
      18, 24 and 34 weeks, for measurement of terminal blood glucose, HbA1c, plasma
      insulin, and C-peptide. Pancreata were removed for quantification of beta cell
      mass, islet numbers as well as proliferation and apoptosis by
      immunohistochemistry and stereology. RESULTS: Total pancreatic beta cell mass
      increased significantly from 2.1 +/- 0.3 mg in mice aged 5 weeks to a peak value
      of 4.84 +/- 0.26 mg (P < 0.05) in 12-week-old mice, then gradually decreased to
      3.27 +/- 0.44 mg in mice aged 34 weeks. Analysis of islets in the 5-, 10-, and 24
      week age groups showed increased beta cell proliferation in the 10-week-old
      animals whereas a low proliferation is seen in older animals. The expansion in
      beta cell mass was driven by an increase in mean islet mass as the total number
      of islets was unchanged in the three groups. CONCLUSIONS/INTERPRETATION: The age
      dependent beta cell dynamics in male db/db mice has been described from 5-34
      weeks of age and at the same time alterations in insulin/glucose homeostasis were
      assessed. High beta cell proliferation and increased beta cell mass occur in
      young animals followed by a gradual decline characterised by a low beta cell
      proliferation in older animals. The expansion of beta cell mass was caused by an
      increase in mean islet mass and not islet number.

PMID- 24324834
TI  - Moderate hypoxia followed by reoxygenation results in blood-brain barrier
      breakdown via oxidative stress-dependent tight-junction protein disruption.
AB  - Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue
      dysfunctional brain areas that are exposed to moderate hypoxia within the
      penumbra from irreversible cell death. Goal of the present study was to evaluate
      the effect of moderate hypoxia followed by reoxygenation (MHR) on the evolution
      of reactive oxygen species (ROS) and blood-brain barrier (BBB) integrity in brain
      endothelial cells (BEC). BBB integrity was assessed in BEC in vitro and in
      microvessels of the guinea pig whole brain in situ preparation. Probes were
      exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC) or towards
      occlusion of the arteria cerebri media (MCAO) with or without subsequent
      reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated
      using trans-endothelial electrical resistance (TEER) and transwell permeability
      assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein
      diacetate (DCF), MitoSox and immunostaining for nitrotyrosine. Tight-junction
      protein (TJ) integrity in BEC, stainings for nitrotyrosine and FITC-albumin
      extravasation in the guinea pig brain preparation were assessed by confocal
      microscopy. Diphenyleneiodonium (DPI) was used to investigate NADPH oxidase
      dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ
      proteins zonula occludens 1 (ZO-1) and claudin 5 (Cl5), decreased TEER, and
      significantly increased cytosolic ROS in BEC. These events were blocked by the
      NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation
      resulted in extravasation of FITC-albumin and ROS generation in the penumbra
      region of the guinea pig brain preparation and confirmed BBB damage. BEC
      integrity may be impaired through ROS in MHR on the level of TJ and the BBB is
      also functionally impaired in moderate hypoxic conditions followed by reperfusion
      in a complex guinea pig brain preparation. These findings suggest that the BBB is
      susceptible towards MHR and that ROS play a key role in this process. 

PMID- 24324835
TI  - Nutrigenomics of high fat diet induced obesity in mice suggests relationships
      between susceptibility to fatty liver disease and the proteasome.
AB  - Nutritional factors play important roles in the etiology of obesity, type 2
      diabetes mellitus and their complications through genotype x environment
      interactions. We have characterised molecular adaptation to high fat diet (HFD)
      feeding in inbred mouse strains widely used in genetic and physiological studies.
      We carried out physiological tests, plasma lipid assays, obesity measures, liver
      histology, hepatic lipid measurements and liver genome-wide gene transcription
      profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet.
      The two strains showed marked susceptibility (C57BL/6J) and relative resistance
      (BALB/c) to HFD-induced insulin resistance and non alcoholic fatty liver disease
      (NAFLD). Global gene set enrichment analysis (GSEA) of transcriptome data
      identified consistent patterns of expression of key genes (Srebf1, Stard4,
      Pnpla2, Ccnd1) and molecular pathways in the two strains, which may underlie
      homeostatic adaptations to dietary fat. Differential regulation of pathways,
      including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling
      in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying
      diet-responsive genes may be involved in contrasting nutrigenomic predisposition
      and resistance to insulin resistance and NAFLD in these models. Collectively,
      these data, which further demonstrate the impact of gene x environment
      interactions on gene expression regulations, contribute to improved knowledge of
      natural and pathogenic adaptive genomic regulations and molecular mechanisms
      associated with genetically determined susceptibility and resistance to metabolic
      diseases. 

PMID- 24324836
TI  - Detection of airway anomalies in pediatric patients with cardiovascular anomalies
      with low dose prospective ECG-gated dual-source CT.
AB  - OBJECTIVES: To assess the feasibility of low-dose prospective ECG-gated dual
      source CT (DSCT) in detecting airway anomalies in pediatric patients with
      cardiovascular anomalies compared with flexible tracheobronchoscopy (FTB).
      METHODS: 33 pediatrics with respiratory symptoms who had been revealed
      cardiovascular anomalies by transthoracic echocardiography underwent FTB and
      contrast material-enhanced prospective ECG-triggering CT were enrolled. The study
      was approved by our institution review board and written informed consent was
      obtained from all patients' guardian. DSCT examinations were performed to detect
      cardiovascular abnormalities using weight-adjusted low-dose protocol. Two
      radiologists independently performed CT image analysis. The FTB reports were
      reviewed by an experienced pulmonologist. The sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and accuracy of DSCT in
      the detection of airway anomalies were assessed. The tracheobronchial stenoses
      revealed on FTB were graded. Effective radiation dose was calculated. RESULTS:
      Thirty cases were diagnosed with tracheobronchial narrowing and/or abnormality in
      33 patients by FTB, while 3 patients had normal FTB findings. Twenty-eight cases
      were diagnosed with airway anomalies by CT, of which 27 were correct positive. 3
      patients with normal findings at CT had findings of tracheobronchial narrowing
      due to tracheobronchomalacia at inspiration at FTB. Sensitivity and specificity
      of CT were 90.0% (95% CI: 72.3%, 97.4%) and 66.7% (95% CI: 12.5 %, 98.2 %),
      respectively. PPV and NPV were 96.4% (95% CI: 79.8 %, 99.8%) and 40.0% (95% CI:
      7.3%, 83.0%), respectively. Overall accuracy of DSCT in detecting airway
      anomalies in pediatrics with cardiovascular anomalies was 87.9% (95% CI: 74.5%,
      97.6%). In grading of tracheobronchial stenosis, images from CT correlated
      closely (r = 0.89) with those of FTB. Mean effective dose was 0.60 +/- 0.20 mSv.
      CONCLUSION: In pediatric patients, ECG-triggered CT to evaluate congenital
      cardiovascular anomalies can also be used to diagnose and characterize fixed
      airway involvement in relation to the vascular structures.

PMID- 24324837
TI  - Brain-stimulation induced blindsight: unconscious vision or response bias?
AB  - A dissociation between visual awareness and visual discrimination is referred to
      as "blindsight". Blindsight results from loss of function of the primary visual
      cortex (V1) which can occur due to cerebrovascular accidents (i.e. stroke-related
      lesions). There are also numerous reports of similar, though reversible, effects
      on vision induced by transcranial Magnetic Stimulation (TMS) to early visual
      cortex. These effects point to V1 as the "gate" of visual awareness and have
      strong implications for understanding the neurological underpinnings of
      consciousness. It has been argued that evidence for the dissociation between
      awareness of, and responses to, visual stimuli can be a measurement artifact of
      the use of a high response criterion under yes-no measures of visual awareness
      when compared with the criterion free forced-choice responses. This difference
      between yes-no and forced-choice measures suggests that evidence for a
      dissociation may actually be normal near-threshold conscious vision. Here we
      describe three experiments that tested visual performance in normal subjects when
      their visual awareness was suppressed by applying TMS to the occipital pole. The
      nature of subjects' performance whilst undergoing occipital TMS was then verified
      by use of a psychophysical measure (d') that is independent of response criteria.
      This showed that there was no genuine dissociation in visual sensitivity measured
      by yes-no and forced-choice responses. These results highlight that evidence for
      visual sensitivity in the absence of awareness must be analysed using a bias-free
      psychophysical measure, such as d', In order to confirm whether or not visual
      performance is truly unconscious. 

PMID- 24324838
TI  - A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection
      severity.
AB  - Influenza viruses pose a significant health risk and annually impose a great cost
      to patients and the health care system. The molecular determinants of influenza
      severity, often exacerbated by secondary bacterial infection, are largely
      unclear. We generated a novel outbred mouse model of influenza virus,
      Staphylococcus aureus, and co-infection utilizing influenza A/CA/07/2009 virus
      and S. aureus (USA300). Outbred mice displayed a wide range of pathologic
      phenotypes following influenza virus or co-infection ranging broadly in severity.
      Influenza viral burden positively correlated with weight loss although lung
      histopathology did not. Inflammatory cytokines including IL-6, TNF-alpha, G-CSF,
      and CXCL10 positively correlated with both weight loss and viral burden. In S.
      aureus infection, IL-1beta, G-CSF, TNF-alpha, and IL-6 positively correlated with
      weight loss and bacterial burden. In co-infection, IL-1beta production correlated
      with decreased weight loss suggesting a protective role. The data demonstrate an
      approach to identify biomarkers of severe disease and to understand pathogenic
      mechanisms in pneumonia. 

PMID- 24324839
TI  - Investigating thought disorder in schizophrenia: evidence for pathological
      activation.
AB  - BACKGROUND: Previous research has yielded evidence for enhanced semantic priming
      in formal thought-disordered schizophrenia patients, a result that fits well with
      the hypothesis of disinhibited processes of spreading activation in this
      population. OBJECTIVE: The current study examined whether hyper priming among
      schizophrenia patients is an outcome of further spreading of activation of a node
      or a result of farther activation of nodes in the semantic network. We also try
      to shed light on the fate of this activation. METHODS: The present study tested
      this hypothesis by using semantic and identical priming in two different
      experiments. SOA (stimulus onset asynchrony) was manipulated (240 ms vs. 740 ms)
      within block. It is assumed that among healthy individuals, performance relies on
      a balance between activation and inhibition processes, contrary to in
      schizophrenic individuals. In order to examine this hypothesis, we compared
      formal thought-disordered schizophrenia patients, non thought-disordered
      schizophrenia patients, and healthy controls. RESULTS: For thought-disordered
      schizophrenia patients, we found a large positive semantic effect and identical
      priming effect (129 ms and 154 ms, respectively) only with short SOA. SOA and
      type of priming did not modulate priming effects in the control groups.
      CONCLUSIONS: This result supports the claim that there is a lack of inhibitory
      processes among thought-disordered patients. Hyper priming in the thought
      disorder group may be an outcome of hyper activation followed by rapid decay
      below baseline threshold.

PMID- 24324840
TI  - Vertebrate dissimilarity due to turnover and richness differences in a highly
      beta-diverse region: the role of spatial grain size, dispersal ability and
      distance.
AB  - We explore the influence of spatial grain size, dispersal ability, and geographic
      distance on the patterns of species dissimilarity of terrestrial vertebrates,
      separating the dissimilarity explained by species replacement (turnover) from
      that resulting from richness differences. With data for 905 species of
      terrestrial vertebrates distributed in the Isthmus of Tehuantepec, classified
      into five groups according to their taxonomy and dispersal ability, we calculated
      total dissimilarity and its additive partitioning as two components:
      dissimilarity derived from turnover and dissimilarity derived from richness
      differences. These indices were compared using fine (10 x 10 km), intermediate
      (20 x 20 km) and coarse (40 x 40 km) grain grids, and were tested for any
      correlations with geographic distance. The results showed that total
      dissimilarity is high for the terrestrial vertebrates in this region. Total
      dissimilarity, and dissimilarity due to turnover are correlated with geographic
      distance, and the patterns are clearer when the grain is fine, which is
      consistent with the distance-decay pattern of similarity. For all terrestrial
      vertebrates tested on the Isthmus of Tehuantepec both the dissimilarity derived
      from turnover and the dissimilarity resulting from richness differences make
      important contributions to total dissimilarity, and dispersal ability does not
      seem to influence the dissimilarity patterns. These findings support the idea
      that conservation efforts in this region require a system of interconnected
      protected areas that embrace the environmental, climatic and biogeographic
      heterogeneity of the area. 

PMID- 24324841
TI  - Ethanol affects the development of sensory hair cells in larval zebrafish (Danio
      rerio).
AB  - Children born to mothers with substantial alcohol consumption during pregnancy
      can present a number of morphological, cognitive, and sensory abnormalities,
      including hearing deficits, collectively known as fetal alcohol syndrome (FAS).
      The goal of this study was to determine if the zebrafish lateral line could be
      used to study sensory hair cell abnormalities caused by exposure to ethanol
      during embryogenesis. Some lateral line sensory hair cells are present at 2 days
      post-fertilization (dpf) and are functional by 5 dpf. Zebrafish embryos were
      raised in fish water supplemented with varying concentrations of ethanol (0.75%
      1.75% by volume) from 2 dpf through 5 dpf. Ethanol treatment during development
      resulted in many physical abnormalities characteristic of FAS in humans. Also,
      the number of sensory hair cells decreased as the concentration of ethanol
      increased in a dose-dependent manner. The dye FM 1-43FX was used to detect the
      presence of functional mechanotransduction channels. The percentage of FM 1-43
      labeled hair cells decreased as the concentration of ethanol increased. Methanol
      treatment did not affect the development of hair cells. The cell cycle markers
      proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU)
      demonstrated that ethanol reduced the number of sensory hair cells, as a
      consequence of decreased cellular proliferation. There was also a significant
      increase in the rate of apoptosis, as determined by TUNEL-labeling, in neuromasts
      following ethanol treatment during larval development. Therefore, zebrafish are a
      useful animal model to study the effects of hair cell developmental disorders
      associated with FAS. 

PMID- 24324842
TI  - Recombinant expression and in vitro characterisation of active Huwentoxin-IV.
AB  - Huwentoxin-IV (HwTx-IV) is a 35-residue neurotoxin peptide with potential
      application as a novel analgesic. It is a member of the inhibitory cystine knot
      (ICK) peptide family, characterised by a compact globular structure maintained by
      three intramolecular disulfide bonds. Here we describe a novel strategy for
      producing non-tagged, fully folded ICK-toxin in a bacterial system. HwTx-IV was
      expressed as a cleavable fusion to small ubiquitin-related modifier (SUMO) in the
      cytoplasm of the SHuffle T7 Express lysY Escherichia coli strain, which allows
      cytosolic disulfide bond formation. Purification by IMAC with selective elution
      of monomeric SUMO fusion followed by proteolytic cleavage and polishing
      chromatographic steps yielded pure homogeneous toxin. Recombinant HwTx-IV is
      produced with a C-terminal acid, whereas the native peptide is C-terminally
      amidated. HwTx-IV(acid) inhibited Nav1.7 in a dose dependent manner (IC50 = 463
      727 nM). In comparison to HwTx-IV(amide) (IC50 = 11 +/- 3 nM), the carboxylate
      was ~50 fold less potent on Nav1.7, which highlights the impact of the C
      terminus. As the amide bond of an additional amino acid may mimic the
      carboxamide, we expressed the glycine-extended analogue HwTx-IV(G36)(acid) in the
      SUMO/SHuffle system. The peptide was approximately three fold more potent on
      Nav1.7 in comparison to HwTx-IV(acid) (IC50 = 190 nM). In conclusion, we have
      established a novel system for expression and purification of fully folded and
      active HwTx-IV(acid) in bacteria, which could be applicable to other structurally
      complex and cysteine rich peptides. Furthermore, we discovered that glycine
      extension of HwTx-IV(acid) restores some of the potency of the native
      carboxamide. This finding may also apply to other C-terminally amidated peptides
      produced recombinantly. 

PMID- 24324843
TI  - Quadriceps and respiratory muscle fatigue following high-intensity cycling in
      COPD patients.
AB  - Exercise intolerance in COPD seems to combine abnormal ventilatory mechanics,
      impaired O2 transport and skeletal muscle dysfunction. However their relative
      contribution and their influence on symptoms reported by patients remain to be
      clarified. In order to clarify the complex interaction between ventilatory and
      neuromuscular exercise limiting factors and symptoms, we evaluated respiratory
      muscles and quadriceps contractile fatigue, dynamic hyperinflation and symptoms
      induced by exhaustive high-intensity cycling in COPD patients. Fifteen gold II
      III COPD patients (age = 67 +/- 6 yr; BMI = 26.6 +/- 4.2 kg.m(-2)) performed
      constant-load cycling test at 80% of their peak workload until exhaustion (9.3 +/
      2.4 min). Before exercise and at exhaustion, potentiated twitch quadriceps
      strength (Q(tw)), transdiaphragmatic (P(di,tw)) and gastric (P(ga,tw)) pressures
      were evoked by femoral nerve, cervical and thoracic magnetic stimulation,
      respectively. Changes in operational lung volumes during exercise were assessed
      via repetitive inspiratory capacity (IC) measurements. Dyspnoea and leg
      discomfort were measured on visual analog scale. At exhaustion, Q(tw) (-33 +/-
      15%, >15% reduction observed in all patients but two) and Pdi,tw (-20 +/- 15%,
      >15% reduction in 6 patients) were significantly reduced (P<0.05) but not Pga,tw
      (-6 +/- 10%, >15% reduction in 3 patients). Percentage reduction in Q(tw)
      correlated with the percentage reduction in P(di,tw) (r = 0.66; P<0.05).
      Percentage reductions in P(di,tw) and P(ga,tw) negatively correlated with the
      reduction in IC at exhaustion (r = -0.56 and r = -0.62, respectively; P<0.05).
      Neither dyspnea nor leg discomfort correlated with the amount of muscle fatigue.
      In conclusion, high-intensity exercise induces quadriceps, diaphragm and less
      frequently abdominal contractile fatigue in this group of COPD patients. In
      addition, the rise in end-expiratory lung volume and diaphragm flattening
      associated with dynamic hyperinflation in COPD might limit the development of
      abdominal and diaphragm muscle fatigue. This study underlines that both
      respiratory and quadriceps fatigue should be considered to understand the complex
      interplay of factors leading to exercise intolerance in COPD patients.

PMID- 24324844
TI  - Biosynthesis of Sandalwood Oil: Santalum album CYP76F cytochromes P450 produce
      santalols and bergamotol.
AB  - Sandalwood oil is one of the world's most highly prized essential oils, appearing
      in many high-end perfumes and fragrances. Extracted from the mature heartwood of
      several Santalum species, sandalwood oil is comprised mainly of sesquiterpene
      olefins and alcohols. Four sesquiterpenols, alpha-, beta-, and epi-beta-santalol
      and alpha-exo-bergamotol, make up approximately 90% of the oil of Santalum album.
      These compounds are the hydroxylated analogues of alpha-, beta-, and epi-beta
      santalene and alpha-exo-bergamotene. By mining a transcriptome database of S.
      album for candidate cytochrome P450 genes, we cloned and characterized cDNAs
      encoding a small family of ten cytochrome P450-dependent monooxygenases annotated
      as SaCYP76F37v1, SaCYP76F37v2, SaCYP76F38v1, SaCYP76F38v2, SaCYP76F39v1,
      SaCYP76F39v2, SaCYP76F40, SaCYP76F41, SaCYP76F42, and SaCYP76F43. Nine of these
      genes were functionally characterized using in vitro assays and yeast in vivo
      assays to encode santalene/bergamotene oxidases and bergamotene oxidases. These
      results provide a foundation for production of sandalwood oil for the fragrance
      industry by means of metabolic engineering, as demonstrated with proof-of-concept
      formation of santalols and bergamotol in engineered yeast cells, simultaneously
      addressing conservation challenges by reducing pressure on supply of sandalwood
      from native forests. 

PMID- 24324845
TI  - Trypanosoma cruzi disrupts thymic homeostasis by altering intrathymic and
      systemic stress-related endocrine circuitries.
AB  - We have previously shown that experimental infection caused by Trypanosoma cruzi
      is associated with changes in the hypothalamus-pituitary-adrenal axis. Increased
      glucocorticoid (GC) levels are believed to be protective against the effects of
      acute stress during infection but result in depletion of CD4(+)CD8(+) thymocytes
      by apoptosis, driving to thymic atrophy. However, very few data are available
      concerning prolactin (PRL), another stress-related hormone, which seems to be
      decreased during T. cruzi infection. Considering the immunomodulatory role of PRL
      upon the effects caused by GC, we investigated if intrathymic cross-talk between
      GC and PRL receptors (GR and PRLR, respectively) might influence T. cruzi-induced
      thymic atrophy. Using an acute experimental model, we observed changes in GR/PRLR
      cross-activation related with the survival of CD4(+)CD8(+) thymocytes during
      infection. These alterations were closely related with systemic changes,
      characterized by a stress hormone imbalance, with progressive GC augmentation
      simultaneously to PRL reduction. The intrathymic hormone circuitry exhibited an
      inverse modulation that seemed to counteract the GC-related systemic deleterious
      effects. During infection, adrenalectomy protected the thymus from the increase
      in apoptosis ratio without changing PRL levels, whereas an additional inhibition
      of circulating PRL accelerated the thymic atrophy and led to an increase in
      corticosterone systemic levels. These results demonstrate that the PRL impairment
      during infection is not caused by the increase of corticosterone levels, but the
      opposite seems to occur. Accordingly, metoclopramide (MET)-induced enhancement of
      PRL secretion protected thymic atrophy in acutely infected animals as well as the
      abnormal export of immature and potentially autoreactive CD4(+)CD8(+) thymocytes
      to the periphery. In conclusion, our findings clearly show that Trypanosoma cruzi
      subverts mouse thymus homeostasis by altering intrathymic and systemic stress
      related endocrine circuitries with major consequences upon the normal process of
      intrathymic T cell development. 

PMID- 24324846
TI  - CASE REPORT How to Repair the Lower Eyelid Retraction, Resulting From the Primary
      Surgery for Epiblepharon?
AB  - OBJECTIVE: Among the surgical procedures used to correct the positions of the
      eyelids or improve their cosmetic appearance, procedures for treating eyelid
      retraction are some of the most challenging. Lower eyelid retraction can occur
      iatrogenically after various surgical procedures. We performed a successful
      corrective procedure for lower eyelid retraction, which had occurred at some
      point in the 2 decades after primary surgery for epiblepharon. METHOD: A 23-year
      old woman underwent primary surgery for bilateral epiblepharon at the age of 5
      years. However, at the age of 17, she noticed that an abnormally large proportion
      of her right sclera was visible when her eyes were in their natural position. In
      the primary position of gaze, the distance from the lower limbus of the right
      cornea to the upper margin of the lower eyelid was approximately 2 mm. An
      incision was made in the lower eyelid along the scar caused by the previous
      operation. Subsequently, the connections between the tarsus and the lower eyelid
      retractors were broken, and harvested auricular cartilage was placed between the
      lower edge of the tarsus and the lower eyelid retractors. RESULTS: One year after
      the operation, there was no gross difference in the distance between the lower
      margin of the corneal limbus and the lower eyelid on either side, and the patient
      was extremely happy with the results. CONCLUSION: Using a novel surgical
      technique, we successfully lengthened the posterior layer of the lower eyelid
      retractors with a small amount auricular cartilage, resulting in good functional
      and cosmetic outcomes.

PMID- 24324847
TI  - Areola size and jugulum nipple distance after bilateral mastectomy and breast
      reconstruction.
AB  - OBJECTIVE: The combination of a single pedicle local flap with tattooing for
      complete nipple areola complex (NAC) reconstruction is currently the most
      supported method. Although many technical descriptions of NAC reconstruction
      exist in the medical literature, there are no data that define the ideal areola
      size (diameter of the areola) after bilateral mastectomy and breast
      reconstruction considering the previous areola size. METHODS: This was a 3-year
      (2009-2012) observational, analytical, and longitudinal prospective study with
      103 patients who had undergone NAC tattooing as the last process of bilateral
      breast reconstruction after surgery for breast cancer. Statistical differences in
      the areola size and the jugulum-nipple distance before mastectomy and after
      reconstruction were analyzed by paired Student t tests with a 95% confidence
      interval. RESULTS: The jugulum-nipple distance before mastectomy was 4.23 cm
      larger than after bilateral reconstruction (mean jugulum-nipple distance: 23.89
      cm vs 19.66 cm), and for that reason shorter (more cephalad). The areola size
      before mastectomy was 1.59 cm larger than the one chosen by the patient for
      reconstruction (mean diameter of the areola: 5.25 cm vs 3.65 cm). CONCLUSIONS: We
      conclude that, after bilateral mastectomy and reconstruction, the jugulum-nipple
      distance is smaller and women prefer smaller areola sizes.

PMID- 24324848
TI  - Direct long bone invasion by Basal cell carcinoma: a case report and review of
      the literature.
AB  - INTRODUCTION: Basal cell carcinoma is the most prevalent form of cancer
      worldwide, usually arising in the head and neck region, which is cured by
      surgical excision and rarely invades or metastasizes. Many reports exist of bony
      invasion in the head and neck but very rarely into long bones. METHODS: We report
      an unusual case of basal cell carcinoma that despite surgical excision, directly
      invaded the left humerus. This article also includes a literature review with
      possible explanations for the occasionally aggressive behavior of basal cell
      carcinoma. RESULTS: This 68-year-old patient underwent wide resection of the
      affected left upper arm skin, tissue, and diaphyseal segment with clear margins.
      The defect was reconstructed with a vascularized free fibula bone graft, pedicled
      latissimus muscle flap, and split-thickness skin graft. CONCLUSIONS: Long bone
      invasion by BCC is extremely rare and not well reported. There are more biologic
      explanations for overtly aggressive behavior that BCC may exhibit such as in this
      case.

PMID- 24324849
TI  - Trigeminal trophic syndrome: report of 2 cases.
AB  - OBJECTIVE: We present 2 cases of trigeminal trophic syndrome treated by surgery.
      METHODS: We performed reconstruction of the ala nasi using a nasolabial flap or
      paramedian forehead flap in combination with an auricular chondrocutaneous
      composite graft. RESULTS: One case was successfully treated. However, ulceration
      recurred intermittently in the other case. CONCLUSIONS: Although trigeminal
      trophic syndrome is rare, we believe that plastic surgeons should have a raised
      awareness of this entity and familiarity with the treatment options.

PMID- 24324850
TI  - Use of an acellular regenerative tissue matrix over chronic wounds.
AB  - OBJECTIVES: Bioengineered skin grafts, including acellular dermal matrices, may
      be effective in treating lower extremity and trunk wounds that are not responsive
      to traditional wound management. Acellular dermal wound matrix is derived from
      human acellular dermal wound matrix (HADWM) tissue and provides a scaffold that
      supports cellular repopulation and revascularization. The major structural
      components of the dermis are retained during processing, and a single application
      has been shown to help achieve wound closure. METHODS: This patient case series
      examined the use of HADWM on lower extremity and trunk wounds in 11 patients (6
      male and 5 female) with a mean age of 55 years (range: 31-83 years). Wounds were
      debrided 1 to 2 times, followed by placement of HADWM (range: 4-330 cm(2)) on
      wounds that varied from the dorsal surface of the foot, lower abdomen, and lower
      extremity to the Achilles flap. A nonadherent layer in conjunction with
      bacitracin was placed over HADWM. Negative pressure wound therapy (NPWT) was
      placed over the HADWM and initiated continuously at -125 mm Hg for 1 to 2 weeks.
      After the application of NPWT, HADWM was covered with various gauze dressings
      using mineral oil. RESULTS: All patients completed their treatment successfully,
      and follow-up ranged from 1 week to 6 months. One patient experienced an
      infection, which resulted in partial graft loss that required replacement with
      HADWM and NPWT. No additional complications occurred in the other patients.
      CONCLUSIONS: This patient case series demonstrated successful use of HADWM and
      NPWT, which further supports published studies documenting HADWM success in
      chronic wounds.

PMID- 24324851
TI  - Negative pressure wound therapy for abdominal wall reconstruction.

PMID- 24324852
TI  - Cerebrospinal fluid leak masquerading as a decubitus ulcer in a patient with
      spina bifida.

PMID- 24324853
TI  - The retrospective chart review: important methodological considerations.
AB  - In this paper, we review and discuss ten common methodological mistakes found in
      retrospective chart reviews. The retrospective chart review is a widely
      applicable research methodology that can be used by healthcare disciplines as a
      means to direct subsequent prospective investigations. In many cases in this
      review, we have also provided suggestions or accessible resources that
      researchers can apply as a "best practices" guide when planning, conducting, or
      reviewing this investigative method. 

PMID- 24324854
TI  - Exploring novel strategies for AIDS protozoal pathogens: alpha-helix mimetics
      targeting a key allosteric protein-protein interaction in C. hominis TS-DHFR.
AB  - The bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR)
      from the protozoal parasite Cryptosporidium hominis is a potential molecular
      target for the design of antiparasitic therapies for AIDS-related opportunistic
      infections. The enzyme exists as a homodimer with each monomer containing a
      unique swap domain known as a "crossover helix" that binds in a cleft on the
      adjacent DHFR active site. This crossover helix is absent in species containing
      monofunctional forms of DHFR such as human. An in-depth understanding of protein
      protein interactions between the crossover helix and adjacent DHFR active site
      that might modulate enzyme integrity or function would allow for insights into
      rational design of species-specific allosteric inhibitors. Mutational analysis
      coupled with structural studies and biophysical and kinetic characterization of
      crossover helix mutants identifies this domain as essential for full enzyme
      stability and catalytic activity, and pinpoints these effects to distinct faces
      of the crossover helix important in protein-protein interactions. Moreover,
      targeting this helical protein interaction with alpha-helix mimetics of the
      crossover helix leads to selective inhibition and destabilization of the C.
      hominis TS-DHFR enzyme, thus validating this region as a new avenue to explore
      for species-specific inhibitor design.

PMID- 24324856
TI  - Polyglandular autoimmune syndrome type 2: diagnosed in the intensive care unit.

PMID- 24324857
TI  - Massive haemoptysis as an unusual symptom in a patient with papillary thyroid
      carcinoma.

PMID- 24324855
TI  - Anti-vascular endothelial growth factor therapy for diabetic macular edema.
AB  - Diabetes mellitus is a serious health problem that affects over 350 million
      individuals worldwide. Diabetic retinopathy (DR), which is the most common
      microvascular complication of diabetes, is the leading cause of new cases of
      blindness in working-aged adults. Diabetic macular edema (DME) is an advanced,
      vision-limiting complication of DR that affects nearly 30% of patients who have
      had diabetes for at least 20 years and is responsible for much of the vision loss
      due to DR. The historic standard of care for DME has been macular laser
      photocoagulation, which has been shown to stabilize vision and reduce the rate of
      further vision loss by 50%; however, macular laser leads to significant vision
      recovery in only 15% of treated patients. Mechanisms contributing to the
      microvascular damage in DR and DME include the direct toxic effects of
      hyperglycemia, sustained alterations in cell signaling pathways, and chronic
      microvascular inflammation with leukocyte-mediated injury. Chronic retinal
      microvascular damage results in elevation of intraocular levels of vascular
      endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific
      mitogen that mediates many important physiologic processes, including but not
      limited to the development and permeability of the vasculature. The
      identification of VEGF as an important pathophysiologic mediator of DME suggested
      that anti-VEGF therapy delivered to the eye might lead to improved visual
      outcomes in this disease. To date, four different inhibitors of VEGF, each
      administered by intraocular injection, have been tested in prospective,
      randomized phase II or phase III clinical trials in patients with DME. The
      results from these trials demonstrate that treatment with anti-VEGF agents
      results in substantially improved visual and anatomic outcomes compared with
      laser photocoagulation, and avoid the ocular side effects associated with laser
      treatment. Thus, anti-VEGF therapy has become the preferred treatment option for
      the management of DME in many patients. 

PMID- 24324858
TI  - Individual heterogeneity in black brant survival and recruitment with
      implications for harvest dynamics.
AB  - We examined individual heterogeneity in survival and recruitment of female
      Pacific black brant (Branta bernicla nigricans) using frailty models adapted to a
      capture-mark-recapture context. Our main objectives were (1) to quantify levels
      of heterogeneity and examine factors affecting heterogeneity, and (2) model the
      effects of individual heterogeneity on harvest dynamics through matrix models. We
      used 24 years of data on brant marked and recaptured at the Tutakoke River
      colony, AK. Multievent models were fit as hidden Markov chain using program E
      SURGE with an adequate overdispersion coefficient. Annual survival of individuals
      marked as goslings was heterogeneous among individuals and year specific with
      about 0.23 difference in survival between "high" (0.73)- and "low" (0.50)-quality
      individuals at average survival probability. Adult survival (0.85 +/- 0.004) was
      homogeneous and higher than survival of both groups of juveniles. The annual
      recruitment probability was heterogeneous for brant >1-year-old; 0.56 (+/-0.21)
      and 0.31 (+/-0.03) for high- and low-quality individuals, respectively. Assuming
      equal clutch sizes for high- and low-quality individuals and that 80% of
      offspring were in the same quality class as the breeding female resulted in
      reproductive values about twice as high for high-quality individuals than low
      quality individual for a given class of individuals producing differential
      contributions to population growth among groups. Differences in reproductive
      values greatly increased when we assumed high-quality individuals had larger
      clutch sizes. When we assumed that 50% of offspring were in the same quality
      class as their mothers and clutches were equal, differences in reproductive
      values between quality classes were greatly reduced or eliminated (breeders
      [BRs]). We considered several harvest scenarios using the assumption that 80% of
      offspring were in the same quality class as their mothers. The amount of
      compensation for harvest mortality declined as the proportion of high-quality
      individuals in the harvest increased, as differences in clutch sizes between
      groups decreased and as the proportion of BRs in the harvest increased. Synthesis
      and applications. Harvest at the same proportional level of the overall
      population can result in variable responses in population growth rate when
      heterogeneity is present in a population. lambda was <1.0 under every scenario
      when harvest rates were >10%, and heterogeneity caused as much as +2% difference
      in growth rates at the highest levels of proportional harvest for low-quality
      individuals and the greatest differences in qualities between classes of
      individuals, a critical difference for a population with lambda near 1.0 such as
      the brant. We observed less response in overall survival in the presence of
      heterogeneity because we did not observe heterogeneity in the annual survival of
      BRs. This analysis provides a comprehensive view of overall compensation at the
      population level and also constitutes the first example of a survival-recruitment
      model with heterogeneity. Individual heterogeneity should be more explicitly
      considered in harvest management of vertebrates. 

PMID- 24324859
TI  - Diet analysis by next-generation sequencing indicates the frequent consumption of
      introduced plants by the critically endangered red-headed wood pigeon (Columba
      janthina nitens) in oceanic island habitats.
AB  - Oceanic island ecosystems are vulnerable to the introduction of alien species,
      and they provide a habitat for many endangered species. Knowing the diet of an
      endangered animal is important for appropriate nature restoration efforts on
      oceanic islands because introduced species may be a major component of the diets
      of some endangered species. DNA barcoding techniques together with next
      generation sequencing may provide more detailed information on animal diets than
      other traditional methods. We performed a diet analysis using 48 fecal samples
      from the critically endangered red-headed wood pigeon that is endemic to the
      Ogasawara Islands based on chloroplast trnL P6 loop sequences. The frequency of
      each detected plant taxa was compared with a microhistological analysis of the
      same sample set. The DNA barcoding approach detected a much larger number of
      plants than the microhistological analysis. Plants that were difficult to
      identify by microhistological analysis after being digested in the pigeon
      stomachs were frequently identified only by DNA barcoding. The results of the
      barcoding analysis indicated the frequent consumption of introduced species, in
      addition to several native species, by the red-headed wood pigeon. The rapid
      eradication of specific introduced species may reduce the food resources
      available to this endangered bird; thus, balancing eradication efforts with the
      restoration of native food plants should be considered. Although some technical
      problems still exist, the trnL approach to next-generation sequencing may
      contribute to a better understanding of oceanic island ecosystems and their
      conservation. 

PMID- 24324860
TI  - Testing the genetic predictions of a biogeographical model in a dominant endemic
      Eastern Pacific coral (Porites panamensis) using a genetic seascape approach.
AB  - The coral fauna of the Eastern Tropical Pacific (ETP) is depauperate and
      peripheral; hence, it has drawn attention to the factors allowing its survival.
      Here, we use a genetic seascape approach and ecological niche modeling to unravel
      the environmental factors correlating with the genetic variation of Porites
      panamensis, a hermatypic coral endemic to the ETP. Specifically, we test if
      levels of diversity and connectivity are higher among abundant than among
      depauperate populations, as expected by a geographically relaxed version of the
      Abundant Center Hypothesis (rel-ACH). Unlike the original ACH, referring to a
      geographical center of distribution of maximal abundance, the rel-ACH refers only
      to a center of maximum abundance, irrespective of its geographic position. The
      patterns of relative abundance of P. panamensis in the Mexican Pacific revealed
      that northern populations from Baja California represent its center of abundance;
      and southern depauperate populations along the continental margin are peripheral
      relative to it. Genetic patterns of diversity and structure of nuclear DNA
      sequences (ribosomal DNA and a single copy open reading frame) and five
      alloenzymatic loci partially agreed with rel-ACH predictions. We found higher
      diversity levels in peninsular populations and significant differentiation
      between peninsular and continental colonies. In addition, continental populations
      showed higher levels of differentiation and lower connectivity than peninsular
      populations in the absence of isolation by distance in each region. Some
      discrepancies with model expectations may relate to the influence of significant
      habitat discontinuities in the face of limited dispersal potential. Environmental
      data analyses and niche modeling allowed us to identify temperature, water
      clarity, and substrate availability as the main factors correlating with patterns
      of abundance, genetic diversity, and structure, which may hold the key to the
      survival of P. panamensis in the face of widespread environmental degradation. 

PMID- 24324862
TI  - Within-colony feeding selectivity by a corallivorous reef fish: foraging to
      maximize reward?
AB  - Foraging theory predicts that individuals should choose a prey that maximizes
      energy rewards relative to the energy expended to access, capture, and consume
      the prey. However, the relative roles of differences in the nutritive value of
      foods and costs associated with differences in prey accessibility are not always
      clear. Coral-feeding fishes are known to be highly selective feeders on
      particular coral genera or species and even different parts of individual coral
      colonies. The absence of strong correlations between the nutritional value of
      corals and prey preferences suggests other factors such as polyp accessibility
      may be important. Here, we investigated within-colony feeding selectivity by the
      corallivorous filefish, Oxymonacanthus longirostris, and if prey accessibility
      determines foraging patterns. After confirming that this fish primarily feeds on
      coral polyps, we examined whether fish show a preference for different parts of a
      common branching coral, Acropora nobilis, both in the field and in the laboratory
      experiments with simulated corals. We then experimentally tested whether
      nonuniform patterns of feeding on preferred coral species reflect structural
      differences between polyps. We found that O. longirostris exhibits nonuniform
      patterns of foraging in the field, selectively feeding midway along branches. On
      simulated corals, fish replicated this pattern when food accessibility was equal
      along the branch. However, when food access varied, fish consistently modified
      their foraging behavior, preferring to feed where food was most accessible. When
      foraging patterns were compared with coral morphology, fish preferred larger
      polyps and less skeletal protection. Our results highlight that patterns of
      interspecific and intraspecific selectivity can reflect coral morphology, with
      fish preferring corals or parts of coral colonies with structural characteristics
      that increase prey accessibility. 

PMID- 24324861
TI  - Functional similarity and molecular divergence of a novel reproductive
      transcriptome in two male-pregnant Syngnathus pipefish species.
AB  - Evolutionary studies have revealed that reproductive proteins in animals and
      plants often evolve more rapidly than the genome-wide average. The causes of this
      pattern, which may include relaxed purifying selection, sexual selection, sexual
      conflict, pathogen resistance, reinforcement, or gene duplication, remain
      elusive. Investigative expansions to additional taxa and reproductive tissues
      have the potential to shed new light on this unresolved problem. Here, we embark
      on such an expansion, in a comparison of the brood-pouch transcriptome between
      two male-pregnant species of the pipefish genus Syngnathus. Male brooding tissues
      in syngnathid fishes represent a novel, nonurogenital reproductive trait,
      heretofore mostly uncharacterized from a molecular perspective. We leveraged next
      generation sequencing (Roche 454 pyrosequencing) to compare transcript abundance
      in the male brooding tissues of pregnant with nonpregnant samples from Gulf (S.
      scovelli) and dusky (S. floridae) pipefish. A core set of protein-coding genes,
      including multiple members of astacin metalloprotease and c-type lectin gene
      families, is consistent between species in both the direction and magnitude of
      expression bias. As predicted, coding DNA sequence analysis of these putative
      "male pregnancy proteins" suggests rapid evolution relative to nondifferentially
      expressed genes and reflects signatures of adaptation similar in magnitude to
      those reported from Drosophila male accessory gland proteins. Although the
      precise drivers of male pregnancy protein divergence remain unknown, we argue
      that the male pregnancy transcriptome in syngnathid fishes, a clade diverse with
      respect to brooding morphology and mating system, represents a unique and
      promising object of study for understanding the perplexing evolutionary nature of
      reproductive molecules. 

PMID- 24324863
TI  - Strong species-environment feedback shapes plant community assembly along
      environmental gradients.
AB  - An aim of community ecology is to understand the patterns of competing species
      assembly along environmental gradients. All species interact with their
      environments. However, theories of community assembly have seldom taken into
      account the effects of species that are able to engineer the environment. In this
      modeling study, we integrate the species' engineering trait together with
      processes of immigration and local dispersal into a theory of community assembly.
      We quantify the species' engineering trait as the degree to which it can move the
      local environment away from its baseline state towards the optimum state of the
      species (species-environment feedback). We find that, in the presence of
      immigration from a regional pool, strong feedback can increase local species
      richness; however, in the absence of continual immigration, species richness is a
      declining function of the strength of species-environment feedback. This shift
      from a negative effect of engineering strength on species richness to a positive
      effect, as immigration rate increases, is clearer when there is spatial
      heterogeneity in the form of a gradient in environmental conditions than when the
      environment is homogeneous or it is randomly heterogeneous. Increasing the scale
      over which local dispersal occurs can facilitate species richness when there is
      no species-environment feedback or when the feedback is weak. However, increases
      in the spatial scale of dispersal can reduce species richness when the species
      environment feedback is strong. These results expand the theoretical basis for
      understanding the effects of the strength of species-environment feedback on
      community assembly. 

PMID- 24324864
TI  - Daphnia predation on the amphibian chytrid fungus and its impacts on disease risk
      in tadpoles.
AB  - Direct predation upon parasites has the potential to reduce infection in host
      populations. For example, the fungal parasite of amphibians, Batrachochytrium
      dendrobatidis (Bd), is commonly transmitted through a free-swimming zoospore
      stage that may be vulnerable to predation. Potential predators of Bd include
      freshwater zooplankton that graze on organisms in the water column. We tested the
      ability of two species of freshwater crustacean (Daphnia magna and D. dentifera)
      to consume Bd and to reduce Bd density in water and infection in tadpoles. In a
      series of laboratory experiments, we allowed Daphnia to graze in water containing
      Bd while manipulating Daphnia densities, Daphnia species identity, grazing
      periods and concentrations of suspended algae (Ankistrodesmus falcatus). We then
      exposed tadpoles to the grazed water. We found that high densities of D. magna
      reduced the amount of Bd detected in water, leading to a reduction in the
      proportion of tadpoles that became infected. Daphnia dentifera, a smaller species
      of Daphnia, also reduced Bd in water samples, but did not have an effect on
      tadpole infection. We also found that algae affected Bd in complex ways. When
      Daphnia were absent, less Bd was detected in water and tadpole samples when
      concentrations of algae were higher, indicating a direct negative effect of algae
      on Bd. When Daphnia were present, however, the amount of Bd detected in water
      samples showed the opposite trend, with less Bd when densities of algae were
      lower. Our results indicate that Daphnia can reduce Bd levels in water and
      infection in tadpoles, but these effects vary with species, algal concentration,
      and Daphnia density. Therefore, the ability of predators to consume parasites and
      reduce infection is likely to vary depending on ecological context. 

PMID- 24324865
TI  - Drosophila rely on learning while foraging under semi-natural conditions.
AB  - Learning is predicted to affect manifold ecological and evolutionary processes,
      but the extent to which animals rely on learning in nature remains poorly known,
      especially for short-lived non-social invertebrates. This is in particular the
      case for Drosophila, a favourite laboratory system to study molecular mechanisms
      of learning. Here we tested whether Drosophila melanogaster use learned
      information to choose food while free-flying in a large greenhouse emulating the
      natural environment. In a series of experiments flies were first given an
      opportunity to learn which of two food odours was associated with good versus
      unpalatable taste; subsequently, their preference for the two odours was assessed
      with olfactory traps set up in the greenhouse. Flies that had experienced
      palatable apple-flavoured food and unpalatable orange-flavoured food were more
      likely to be attracted to the odour of apple than flies with the opposite
      experience. This was true both when the flies first learned in the laboratory and
      were then released and recaptured in the greenhouse, and when the learning
      occurred under free-flying conditions in the greenhouse. Furthermore, flies
      retained the memory of their experience while exploring the greenhouse overnight
      in the absence of focal odours, pointing to the involvement of consolidated
      memory. These results support the notion that even small, short lived insects
      which are not central-place foragers make use of learned cues in their natural
      environments. 

PMID- 24324866
TI  - Inferring parturition and neonate survival from movement patterns of female
      ungulates: a case study using woodland caribou.
AB  - Analyses of animal movement data have primarily focused on understanding patterns
      of space use and the behavioural processes driving them. Here, we analyzed animal
      movement data to infer components of individual fitness, specifically parturition
      and neonate survival. We predicted that parturition and neonate loss events could
      be identified by sudden and marked changes in female movement patterns. Using GPS
      radio-telemetry data from female woodland caribou (Rangifer tarandus caribou), we
      developed and tested two novel movement-based methods for inferring parturition
      and neonate survival. The first method estimated movement thresholds indicative
      of parturition and neonate loss from population-level data then applied these
      thresholds in a moving-window analysis on individual time-series data. The second
      method used an individual-based approach that discriminated among three a priori
      models representing the movement patterns of non-parturient females, females with
      surviving offspring, and females losing offspring. The models assumed that step
      lengths (the distance between successive GPS locations) were exponentially
      distributed and that abrupt changes in the scale parameter of the exponential
      distribution were indicative of parturition and offspring loss. Both methods
      predicted parturition with near certainty (>97% accuracy) and produced
      appropriate predictions of parturition dates. Prediction of neonate survival was
      affected by data quality for both methods; however, when using high quality data
      (i.e., with few missing GPS locations), the individual-based method performed
      better, predicting neonate survival status with an accuracy rate of 87%.
      Understanding ungulate population dynamics often requires estimates of
      parturition and neonate survival rates. With GPS radio-collars increasingly being
      used in research and management of ungulates, our movement-based methods
      represent a viable approach for estimating rates of both parameters. 

PMID- 24324867
TI  - Manipulating reproductive effort leads to changes in female reproductive
      scheduling but not oxidative stress.
AB  - The trade-off between reproductive investment and lifespan is the single most
      important concept in life-history theory. A variety of sources of evidence
      support the existence of this trade-off, but the physiological costs of
      reproduction that underlie this relationship remain poorly understood. The Free
      Radical Theory of Ageing suggests that oxidative stress, which occurs when there
      is an imbalance between the production of damaging Reactive Oxygen Species (ROS)
      and protective antioxidants, may be an important mediator of this trade-off. We
      sought to test this theory by manipulating the reproductive investment of female
      mice (Mus musculus domesticus) and measuring the effects on a number of life
      history and oxidative stress variables. Females with a greater reproductive load
      showed no consistent increase in oxidative damage above females who had a smaller
      reproductive load. The groups differed, however, in their food consumption,
      reproductive scheduling and mean offspring mass. Of particular note, females with
      a very high reproductive load delayed blastocyst implantation of their second
      litter, potentially mitigating the costs of energetically costly reproductive
      periods. Our results highlight that females use strategies to offset particularly
      costly periods of reproduction and illustrate the absence of a simple
      relationship between oxidative stress and reproduction. 

PMID- 24324868
TI  - Congruent morphological and genetic differentiation as a signature of range
      expansion in a fragmented landscape.
AB  - Phenotypic differentiation is often interpreted as a result of local adaptation
      of individuals to their environment. Here, we investigated the skull
      morphological differentiation in 11 populations of the white-footed mouse
      (Peromyscus leucopus). These populations were sampled in an agricultural
      landscape in the Monteregie region (Quebec, Canada), at the northern edge of the
      distribution of the white-footed mouse. We found a strong pattern of phenotypic
      differentiation matching the genetic structure across these populations.
      Landscape fragmentation and the presence of geographic barriers, in particular
      north-south oriented rivers, contribute to this differentiation and modulate the
      pattern of rapid ongoing northward range expansion of the white-footed mouse in
      response to climate warming. We conclude that while large rivers and postglacial
      recolonization routes have shaped the current pattern of distribution and
      differentiation of white-footed mouse populations, further local differentiation
      is occurring, at the scale of the landscape. We posit that the northern expansion
      of the white-footed mouse is achieved through successive independent founder
      events in a fragmented landscape at the northern range edge of the species. The
      phenotypic differentiation we observe is thus a result of a number of mechanisms
      operating at different spatial and temporal scales. 

PMID- 24324869
TI  - Forest insects and climate change: long-term trends in herbivore damage.
AB  - Long-term data sets, covering several decades, could help to reveal the effects
      of observed climate change on herbivore damage to plants. However, sufficiently
      long time series in ecology are scarce. The research presented here analyzes a
      long-term data set collected by the Hungarian Forest Research Institute over the
      period 1961-2009. The number of hectares with visible defoliation was estimated
      and documented for several forest insect pest species. This resulted in a unique
      time series that provides us with the opportunity to compare insect damage trends
      with trends in weather patterns. Data were analyzed for six lepidopteran species:
      Thaumetopoea processionea, Tortrix viridana, Rhyacionia buoliana, Malacosoma
      neustria, Euproctis chrysorrhoea, and Lymantria dispar. All these species exhibit
      outbreak dynamics in Hungary. Five of these species prefer deciduous tree species
      as their host plants, whereas R. buoliana is a specialist on Pinus spp. The data
      were analyzed using general linear models and generalized least squares
      regression in relation to mean monthly temperature and precipitation. Temperature
      increased considerably, especially over the last 25 years (+1.6 degrees C),
      whereas precipitation exhibited no trend over the period. No change in weather
      variability over time was observed. There was increased damage caused by two
      species on deciduous trees. The area of damage attributed to R. buoliana
      decreased over the study period. There was no evidence of increased variability
      in damage. We conclude that species exhibiting a trend toward outbreak-level
      damage over a greater geographical area may be positively affected by changes in
      weather conditions coinciding with important life stages. Strong associations
      between the geographical extent of severe damage and monthly temperature and
      precipitation are difficult to confirm, studying the life-history traits of
      species could help to increase understanding of responses to climate change. 

PMID- 24324870
TI  - Modelling shifts in agroclimate and crop cultivar response under climate change.
AB  - THIS PAPER AIMS: (i) to identify at national scale areas where crop yield
      formation is currently most prone to climate-induced stresses, (ii) to evaluate
      how the severity of these stresses is likely to develop in time and space, and
      (iii) to appraise and quantify the performance of two strategies for adapting
      crop cultivation to a wide range of (uncertain) climate change projections. To
      this end we made use of extensive climate, crop, and soil data, and of two
      modelling tools: N-AgriCLIM and the WOFOST crop simulation model. N-AgriCLIM was
      developed for the automatic generation of indicators describing basic
      agroclimatic conditions and was applied over the whole of Finland. WOFOST was
      used to simulate detailed crop responses at four representative locations. N
      AgriCLIM calculations have been performed nationally for 3829 grid boxes at a 10
      * 10 km resolution and for 32 climate scenarios. Ranges of projected shifts in
      indicator values for heat, drought and other crop-relevant stresses across the
      scenarios vary widely - so do the spatial patterns of change. Overall, under
      reference climate the most risk-prone areas for spring cereals are found in south
      west Finland, shifting to south-east Finland towards the end of this century.
      Conditions for grass are likely to improve. WOFOST simulation results suggest
      that CO2 fertilization and adjusted sowing combined can lead to small yield
      increases of current barley cultivars under most climate scenarios on favourable
      soils, but not under extreme climate scenarios and poor soils. This information
      can be valuable for appraising alternative adaptation strategies. It facilitates
      the identification of regions in which climatic changes might be rapid or
      otherwise notable for crop production, requiring a more detailed evaluation of
      adaptation measures. The results also suggest that utilizing the diversity of
      cultivar responses seems beneficial given the high uncertainty in climate change
      projections.

PMID- 24324871
TI  - Band reporting rates of waterfowl: does individual heterogeneity bias estimated
      survival rates?
AB  - In capture-recapture studies, the estimation accuracy of demographic parameters
      is essential to the efficacy of management of hunted animal populations. Dead
      recovery models based upon the reporting of rings or bands are often used for
      estimating survival of waterfowl and other harvested species. However, distance
      from the ringing site or condition of the bird may introduce substantial
      individual heterogeneity in the conditional band reporting rates (r), which could
      cause bias in estimated survival rates (S) or suggest nonexistent individual
      heterogeneity in S. To explore these hypotheses, we ran two sets of simulations
      (n = 1000) in MARK using Seber's dead recovery model, allowing time variation on
      both S and r. This included a series of heterogeneity models, allowing
      substantial variation on logit(r), and control models with no heterogeneity. We
      conducted simulations using two different values of S: S = 0.60, which would be
      typical of dabbling ducks such as mallards (Anas platyrhynchos), and S = 0.80,
      which would be more typical of sea ducks or geese. We chose a mean reporting rate
      on the logit scale of -1.9459 with SD = 1.5 for the heterogeneity models
      (producing a back-transformed mean of 0.196 with SD = 0.196, median = 0.125) and
      a constant reporting rate for the control models of 0.196. Within these sets of
      simulations, estimation models where sigmaS = 0 and sigmaS > 0 (sigmaS is SD of
      individual survival rates on the logit scale) were incorporated to investigate
      whether real heterogeneity in r would induce apparent individual heterogeneity in
      S. Models where sigmaS = 0 were selected approximately 91% of the time over
      models where sigmaS > 0. Simulation results showed < 0.05% relative bias in
      estimating survival rates except for models estimating sigmaS > 0 when true S =
      0.8, where relative bias was a modest 0.5%. These results indicate that
      considerable variation in reporting rates does not cause major bias in estimated
      survival rates of waterfowl, further highlighting the robust nature of dead
      recovery models that are being used for the management of harvested species. 

PMID- 24324872
TI  - Degrading habitats and the effect of topographic complexity on risk assessment.
AB  - Topographic complexity is a key component of habitats that influences communities
      by modulating the interactions among individuals that drive population processes
      such as recruitment, competition, and predation. A broad range of disturbance
      agents affect biological communities indirectly through their modifications to
      habitat complexity. Individuals that best judge the threat of predation within
      their environment and can trade-off vigilance against behaviors that promote
      growth will be rewarded with the highest fitness. This study experimentally
      examined whether topographic habitat complexity affected the way a damselfish
      assessed predation risk using olfactory, visual, or combined cues. Fish had
      higher feeding rates in the low complexity environment. In a low complexity
      environment, damage-released olfactory cues and visual cues of predators
      complemented each other in the prey's assessment of risk. However, where
      complexity was high and visual cues obscured, prey had lower feeding rates and
      relied more heavily on olfactory cues for risk assessment. Overall, fish appear
      to be more conservative in the high complexity treatment. Low complexity promoted
      extremes of behavior, with higher foraging activity but a greater response to
      predation threats compared with the high complexity treatment. The degree of
      flexibility that individuals and species have in their ability to adjust the
      balance of senses used in risk assessment will determine the extent to which
      organisms will tolerate modifications to their habitat through disturbance. 

PMID- 24324873
TI  - Effects of inbreeding on fitness-related traits in a small isolated moose
      population.
AB  - Inbreeding can affect fitness-related traits at different life history stages and
      may interact with environmental variation to induce even larger effects. We used
      genetic parentage assignment based on 22 microsatellite loci to determine a 25
      year long pedigree for a newly established island population of moose with 20-40
      reproducing individuals annually. We used the pedigree to calculate individual
      inbreeding coefficients and examined for effects of individual inbreeding (f) and
      heterozygosity on fitness-related traits. We found negative effects of f on birth
      date, calf body mass and twinning rate. The relationship between f and calf body
      mass and twinning rate were found to be separate but weaker after accounting for
      birth date. We found no support for an inbreeding effect on the age-specific
      lifetime reproductive success of females. The influence of f on birth date was
      related to climatic conditions during the spring prior to birth, indicating that
      calves with a low f were born earlier after a cold spring than calves with high
      f. In years with a warm spring, calf f did not affect birth date. The results
      suggest that severe inbreeding in moose has both indirect effects on fitness
      through delayed birth and lower juvenile body mass, as well as separate direct
      effects, as there still was a significant relationship between f and twinning
      rate after accounting for birth date and body mass as calf. Consequently, severe
      inbreeding as found in the study population may have consequences for population
      growth and extinction risk. 

PMID- 24324874
TI  - Partitioning of soil phosphorus regulates competition between Vaccinium vitis
      idaea and Deschampsia cespitosa.
AB  - It has been hypothesized that the wide range of forms and complexities of
      phosphorus (P) in soil may result in resource partitioning that contributes to
      the maintenance of plant species diversity. Here, we test whether the graminoid,
      Deschampsia cespitosa, and the ericaceous shrub, Vaccinium vitis-idaea, which
      often coexist, display preferences in utilization of P forms, and differ in their
      production of extracellular P-degrading enzymes. We provided plants with no
      additional P, or P forms with decreasing lability, namely sodium phosphate (SP),
      D-glucose 6 phosphate (DG6P), sodium phytate (PASS), and a combination of SP,
      DG6P, and PASS. We also tested if preferences for P forms affected the
      competitive outcomes between the two species compared between conspecifics, as
      indicated by shoot biomass and acquisition of nitrogen (N) and P. Both D.
      cespitosa and V. vitis-idaea produced the greatest biomass when supplied with a
      mix of all three forms of P. Of the three forms of P tested alone, shoot biomass
      produced by both species was least when supplied with SP. D. cespitosa performed
      better when grown with PASS or a mix of all P forms compared with the performance
      of V. vitis-idaea on these substrates. This was reflected by substantially
      greater phytase activity on the surface of its roots compared with V. vitis
      idaea. In contrast, V. vitis-idaea produced more phosphomonoesterase to hydrolyze
      the simple organic P form, DG6P. Although N was kept constant in the treatments,
      the ability of plants to acquire it was dependent on species identity,
      competition, and P supply. These findings provide direct evidence for preferences
      toward specific forms of P and indicate a key role played by organic forms of P.
      The results support the idea that partitioning for soil P is one factor
      regulating plant competition, and ultimately, community composition. Our data
      also highlight the importance of the interplay between P supply and N
      acquisition. 

PMID- 24324875
TI  - Patterns and dynamics of rapid local adaptation and sex in varying habitat types
      in rotifers.
AB  - Local adaptation is an important principle in a world of environmental change and
      might be critical for species persistence. We tested the hypothesis that
      replicated populations can attain rapid local adaptation under two varying
      laboratory environments. Clonal subpopulations of the cyclically parthenogenetic
      rotifer Brachionus calyciflorus were allowed to adapt to two varying harsh and a
      benign environment: a high-salt, a food-limited environment and untreated culture
      medium (no salt addition, high food). In contrast to most previous studies, we re
      adjusted rotifer density to a fixed value (two individuals per ml) every 3-4 days
      of unrestricted population growth, instead of exchanging a fixed proportion of
      the culture medium. Thus our dilution regime specifically selected for high
      population growth during the entire experiment and it allowed us to continuously
      track changes in fitness (i.e., maximum population growth under the prevailing
      conditions) in each population. After 56 days (43 asexual and eight sexual
      generations) of selection, the populations in the harsh environments showed a
      significant increase in fitness over time relative to the beginning compared to
      the population in untreated culture medium. Furthermore, the high-salt population
      exhibited a significantly elevated ratio of sexual offspring from the start of
      the experiment, which suggested that this environment either triggered higher
      rates of sex or that the untreated medium and the food-limited environment
      suppressed sex. In a following assay of local adaptation we measured population
      fitness under "local" versus "foreign" conditions (populations adapted to this
      environment compared to those of the other environment) for both harsh habitats.
      We found significantly higher fitness values for the local populations (on
      average, a 38% higher fitness) compared to the foreign populations. Overall,
      local adaptation was formed rapidly and it seemed to be more pronounced in the
      high-salt treatment. 

PMID- 24324876
TI  - Targeting hunter distribution based on host resource selection and kill sites to
      manage disease risk.
AB  - Endemic and emerging diseases are rarely uniform in their spatial distribution or
      prevalence among cohorts of wildlife. Spatial models that quantify risk-driven
      differences in resource selection and hunter mortality of animals at fine spatial
      scales can assist disease management by identifying high-risk areas and
      individuals. We used resource selection functions (RSFs) and selection ratios
      (SRs) to quantify sex- and age-specific resource selection patterns of collared
      (n = 67) and hunter-killed (n = 796) nonmigratory elk (Cervus canadensis
      manitobensis) during the hunting season between 2002 and 2012, in southwestern
      Manitoba, Canada. Distance to protected area was the most important covariate
      influencing resource selection and hunter-kill sites of elk (AICw = 1.00).
      Collared adult males (which are most likely to be infected with bovine
      tuberculosis (Mycobacterium bovis) and chronic wasting disease) rarely selected
      for sites outside of parks during the hunting season in contrast to adult females
      and juvenile males. The RSFs showed selection by adult females and juvenile males
      to be negatively associated with landscape-level forest cover, high road density,
      and water cover, whereas hunter-kill sites of these cohorts were positively
      associated with landscape-level forest cover and increasing distance to streams
      and negatively associated with high road density. Local-level forest was
      positively associated with collared animal locations and hunter-kill sites;
      however, selection was stronger for collared juvenile males and hunter-killed
      adult females. In instances where disease infects a metapopulation and
      eradication is infeasible, a principle goal of management is to limit the spread
      of disease among infected animals. We map high-risk areas that are regularly used
      by potentially infectious hosts but currently underrepresented in the
      distribution of kill sites. We present a novel application of widely available
      data to target hunter distribution based on host resource selection and kill
      sites as a promising tool for applying selective hunting to the management of
      transmissible diseases in a game species. 

PMID- 24324877
TI  - Individual differences in migratory behavior shape population genetic structure
      and microhabitat choice in sympatric blackcaps (Sylvia atricapilla).
AB  - In migratory birds, traits such as orientation and distance are known to have a
      strong genetic background, and they often exhibit considerable within-population
      variation. How this variation relates to evolutionary responses to ongoing
      selection is unknown because the underlying mechanisms that translate
      environmental changes into population genetic changes are unclear. We show that
      within-population genetic structure in southern German blackcaps (Sylvia
      atricapilla) is related to individual differences in migratory behavior. Our 3
      year study revealed a positive correlation between individual migratory origins,
      denoted via isotope (delta (2)H) values, and genetic distances. Genetic diversity
      and admixture differed not only across a recently established migratory
      polymorphism with NW- and SW-migrating birds but also across delta (2)H clusters
      within the same migratory route. Our results suggest assortment based on
      individual migratory origins which would facilitate evolutionary responses. We
      scrutinized arrival times and microhabitat choice as potential mechanisms
      mediating between individual variation in migratory behavior and assortment. We
      found significant support that microhabitat choice, rather than timing of
      arrival, is associated with individual variation in migratory origins. Moreover,
      examining genetic diversity across the migratory divide, we found migrants
      following the NW route to be genetically more distinct from each other compared
      with migrants following the traditional SW route. Our study suggests that
      migratory behavior shapes population genetic structure in blackcaps not only
      across the migratory divide but also on an individual level independent of the
      divide. Thus, within-population variation in migratory behavior might play an
      important role in translating environmental change into genetic change. 

PMID- 24324879
TI  - The role of activated acetate intermediates in the control of Escherichia coli
      biofilm amounts.
AB  - A previous study postulated that acetate metabolism was a metabolic sensory
      mechanism that related information about E. coli's environment to the formation
      of biofilms (Prubeta et al., Arch. Microbiol. 2010). Considering that mutants in
      pta ackA (no acetyl phosphate) and ackA (high acetyl phosphate) exhibited
      similarly increased biofilm amounts and three dimensional structures, the
      hypothesis for this study was that acetyl Co-A was a more likely mediator of the
      acetate effect than acetyl phosphate. The effect of acetate metabolism on biofilm
      amounts was detailed by using single carbon sources rather than the previously
      used mixed amino acid medium, as well as mutations in additional genes that
      contribute to acetate metabolism (ldhA, pflA, pflB). In summary, the mutations in
      ackA, pta ackA, and ldhA increased biofilm amounts in the presence of maltose, D
      trehalose, D-mannose, and L-rhamnose, all of which get converted to acetyl-CoA.
      The ackA mutant also exhibited increased biofilm amounts in the presence of
      inosine and thymidine. The mutation in pflA decreased biofilm amounts in the
      presence of maltotriose, uridine, D-serine, and acetate. Since ackA, pta ackA,
      and ldhA mutants are expected to exhibit increased intracellular acetyl-CoA
      levels, and pflA and pflB mutants likely exhibit decreased acetyl-CoA
      concentrations, we believe that acetyl-CoA is the activated acetate intermediate
      that controls biofilm amounts.

PMID- 24324881
TI  - Childhood obesity: today and tomorrow's health challenge.

PMID- 24324880
TI  - Is spectral-domain optical coherence tomography essential for flexible treatment
      regimens with ranibizumab for neovascular age-related macular degeneration?
AB  - Purpose. To evaluate the ability of spectral-domain optical coherence tomography
      to detect subtle amounts of retinal fluid when the choroidal neovascularization
      is detected as inactive via time-domain optical coherence tomography and clinical
      examination in neovascular age-related macular degeneration (nAMD) patients.
      Methods. Forty-nine eyes of 49 patients with nAMD after ranibizumab treatment
      were included in this cross-sectional, prospective study. All patients were
      imaged with TD-OCT and SD-OCT at the same visit one month after a ranibizumab
      injection. The presence of subretinal, intraretinal, and subretinal pigment
      epithelium fluid (subRPE) in SD-OCT was evaluated; also mean central retinal
      thickness (CRT) and the rate of vitreoretinal surface disorders detected via the
      two devices were evaluated. Results. The mean CRT via TD-OCT and SD-OCT was 218.1
      +/- 51.3 and 325.7 +/- 78.8 microns. Sixteen patients (32.6%) showed any kind of
      retinal fluid via SD-OCT. In detail, 8 patients (16.3%) showed subretinal fluid,
      10 patients (20.4%) showed intraretinal fluid, and 3 patients (6.1%) showed
      SubRPE fluid. The ability of detecting vitreoretinal surface disorders was
      comparable between the two devices, except vitreomacular traction. Conclusion. SD
      OCT is essential for the nAMD patients who are on an as-needed treatment regimen
      with ranibizumab. Only TD-OCT and clinical examination may cause insufficient
      treatment in this group of patients. 

PMID- 24324882
TI  - Mental Health Outcomes in US Children and Adolescents Born Prematurely or with
      Low Birthweight.
AB  - We examined the effects of prematurity (<37 weeks of gestation) and low
      birthweight (<2500 g) on mental health outcomes among US children aged 2-17
      years. The 2011-2012 National Survey of Children's Health (N = 95,677) was used
      to estimate prevalence of parent-reported mental health problems in children.
      Prevalence of mental disorders was 22.9% among children born prematurely, 28.7%
      among very-low-birth-weight (<1500 g) children, and 18.9% among moderately low
      birth-weight (1500-2499 g) children, compared with 15.5% in the general child
      population. Compared to those born full term, children born prematurely had 61%
      higher adjusted odds of serious emotional/behavioral problems, 33% higher odds of
      depression, and 58% higher odds of anxiety. Children born prematurely had 2.3
      times higher odds of autism/ASD, 2.9 times higher odds of development delay, and
      2.7 times higher odds of intellectual disability than term children. Very-low
      birth-weight children had 3.2 times higher odds of autism/ASD, 1.7 times higher
      odds of ADD/ADHD, 5.4 times higher odds of development delay, and 4.4 times
      higher odds of intellectual disability than normal-birth-weight children. Social
      factors were significant predictors of mental disorders in both premature/low
      birth-weight and term/normal-birth-weight children. Neurodevelopmental conditions
      accounted for the relationship between prematurity and depression/anxiety/conduct
      problems. Prematurity and low birthweight are significant risk factors for mental
      health problems among children. 

PMID- 24324883
TI  - The Impact of an Early Eclectic Rehabilitative Intervention on Symptoms in First
      Episode Depression among Employed People.
AB  - Objective. To evaluate the effect of an early vocational-orientated eclectic
      intervention on beck depression inventory (BDI) scores compared to treatment as
      usual in first ever depressive episode among employed people. Design. A
      randomized controlled trial comparing the rehabilitative intervention and the
      conventional treatment. Subjects. The subjects came from occupational health care
      units. Methods. Employees were sent to a rehabilitation center after being
      screened for depression using the BDI. They were diagnosed using the structured
      clinical interview for DSM-IV. The participating subjects (N = 283) were
      randomized into intervention and control groups. The intervention group received
      eclectic early depression intervention treatment (N = 134) and the control group
      was treated in the conventional way (N = 100). They were followed for one year.
      Results. The mean decrease in BDI scores within the intervention group was from
      20.8 to 11.6 and within the control group from 19.3 to 10.8. BDI score decreased
      by 10 or more points in 64% of the participants in the intervention group and in
      53% of the control group (P = 0.013). Conclusions. There was some evidence that
      early eclectic intervention in first ever episode depression may be more
      effective than conventional treatments among working age people in employment. 

PMID- 24324884
TI  - Cholinergic Depletion in Alzheimer's Disease Shown by [ (18) F]FEOBV
      Autoradiography.
AB  - Rationale. Alzheimer's Disease (AD) is a neurodegenerative condition
      characterized in part by deficits in cholinergic basalocortical and
      septohippocampal pathways. [(18)F]Fluoroethoxybenzovesamicol ([(18)F]FEOBV), a
      Positron Emission Tomography ligand for the vesicular acetylcholine transporter
      (VAChT), is a potential molecular agent to investigate brain diseases associated
      with presynaptic cholinergic losses. Purpose. To demonstrate this potential, we
      carried out an [(18)F]FEOBV autoradiography study to compare postmortem brain
      tissues from AD patients to those of age-matched controls. Methods. [(18)F]FEOBV
      autoradiography binding, defined as the ratio between regional grey and white
      matter, was estimated in the hippocampus (13 controls, 8 AD) and prefrontal
      cortex (13 controls, 11 AD). Results. [(18)F]FEOBV binding was decreased by 33%
      in prefrontal cortex, 25% in CA3, and 20% in CA1. No changes were detected in the
      dentate gyrus of the hippocampus, possibly because of sprouting or upregulation
      toward the resilient glutamatergic neurons of the dentate gyrus. Conclusion. This
      is the first demonstration of [(18)F]FEOBV focal binding changes in cholinergic
      projections to the cortex and hippocampus in AD. Such cholinergic synaptic (and
      more specifically VAChT) alterations, in line with the selective basalocortical
      and septohippocampal cholinergic losses documented in AD, indicate that
      [(18)F]FEOBV is indeed a promising ligand to explore cholinergic abnormalities in
      vivo. 

PMID- 24324886
TI  - Inhibition of rat muscle and liver phosphofructokinases by high doses of ethanol.
AB  - Activities of both rat muscle and liver phosphofructokinases are significantly
      inhibited after a single ethanol intake in the dose of 2.5 g per kg of body
      weight. This inhibitory effect is indirect, since ethanol in concentration (50
      mM) close to that established after 2.5 g per kg of body weight intake cannot
      decrease their activities in vitro. Inhibition of liver phosphofructokinase
      activity after the 5.0 g per kg ethanol intake may be direct, since liver
      phosphofructokinase activity decreases in vitro when ethanol is added to
      supernatants of rat liver tissue in 100 mM concentration. According to the
      results of molecular docking, ethanol at high concentrations can be bound by
      adenine-binding pocket of the allosteric ADP-binding site of liver
      phosphofructokinase (Asp543, Phe308, Phe538, and Phe671) and its activation by
      ADP can be blocked by C2H5OH molecule. Direct inhibition of muscle
      phosphofructokinase activity, probably due to the binding of ethanol to the
      similar ADP-binding site, is possible when the concentration of ethanol (500 mM)
      is much higher than the level which can be established in living cells. So,
      inhibition of muscle phosphofructokinase activity after a single 5.0 g per kg
      intake is indirect and probably linked with the inhibition of the enzyme by
      elevated citrate and phosphoenolpyruvate levels. 

PMID- 24324887
TI  - Determination of coverage interval of antioxidant vitamins (vitamin C & vitamin
      e) in plasma and serum of bengali population.
AB  - Reference interval of all haematological and biological analytes should be
      measured for every population because of the huge diversity in genetic make-up,
      dietary habits. The coverage interval of antioxidant vitamins (vitamin C and
      alpha -tocopherol) in the plasma and serum of reference Bengali population was
      determined and compared with the reference intervals of antioxidant vitamins in
      the established literature. Adult healthy volunteers from 18 to 68 years of age
      underwent extensive clinical and investigational procedure and were included in
      the study. Vitamin C and alpha -tocopherol were estimated using simple
      Spectrophotometric method. Of the 71 healthy Bengali volunteers participated, 31
      were males and 40 were females. The mean concentration of plasma vitamin C was
      found to be 0.65 mg/dL. The mean alpha -tocopherol was found 6.35 mg/L (14.74  MU
      mol/L) in the study population higher than the normal threshold value for alpha 
      tocopherol but lower than other populations. The study data enabled us to
      determine the gender nonspecific coverage interval of antioxidant vitamins, and
      the intervals were lower than the established reference interval in other
      populations. 

PMID- 24324885
TI  - Defects in tendon, ligament, and enthesis in response to genetic alterations in
      key proteoglycans and glycoproteins: a review.
AB  - This review summarizes the genetic alterations and knockdown approaches published
      in the literature to assess the role of key proteoglycans and glycoproteins in
      the structural development, function, and repair of tendon, ligament, and
      enthesis. The information was collected from (i) genetically altered mice, (ii)
      in vitro knockdown studies, (iii) genetic variants predisposition to injury, and
      (iv) human genetic diseases. The genes reviewed are for small leucine-rich
      proteoglycans (lumican, fibromodulin, biglycan, decorin, and asporin); dermatan
      sulfate epimerase (Dse) that alters structure of glycosaminoglycan and hence the
      function of small leucine-rich proteoglycans by converting glucuronic to iduronic
      acid; matricellular proteins (thrombospondin 2, secreted phosphoprotein 1 (Spp1),
      secreted protein acidic and rich in cysteine (Sparc), periostin, and tenascin X)
      including human tenascin C variants; and others, such as tenomodulin, leukocyte
      cell derived chemotaxin 1 (chondromodulin-I, ChM-I), CD44 antigen (Cd44),
      lubricin (Prg4), and aggrecan degrading gene, a disintegrin-like and
      metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 5 (Adamts5).
      Understanding these genes represents drug targets for disrupting pathological
      mechanisms that lead to tendinopathy, ligamentopathy, enthesopathy, enthesitis
      and tendon/ligament injury, that is, osteoarthritis and ankylosing spondylitis. 

PMID- 24324888
TI  - Increased Female MS Incidence and Differences in Gender-Specific Risk in Medium-
      and High-Risk Regions in Finland from 1981-2010.
AB  - Background. MS incidence has increased among females, suggesting the presence of
      environmental effect. Object. Regional differences and temporal changes in gender
      specific MS incidence were studied in Finland. Methods. Cases from Jan 1, 1981 to
      Dec 31, 2010 in Pirkanmaa, Seinajoki and Vaasa districts were included. The
      standardized incidence rates (SIR), incidences per 10(5) person years with 95%
      confidence intervals (CI), and female-to-male ratios (F/M) were determined by
      district. Results. 1617 cases were included. Compared to Pirkanmaa, the MS risk
      was 1.9-fold (95% CI: 1.7-2.0) greater in Seinajoki and 1.2-fold (95% CI: 1.1
      1.4) in Vaasa, and the risk was high for both genders. The incidence trend
      stabilized in Seinajoki and Vaasa, accompanied by an increase in the F/M ratio. A
      steady increase in Pirkanmaa was accompanied by a high F/M ratio. Conclusion. A
      high female preponderance accompanied a general increase in incidence since the
      1990s, suggesting the influence of environmental factors. In high-risk districts,
      increased MS risk prevailed in both genders. High risk reflects both genetic and
      environmental effects. These effects may be shared with autoimmune diseases such
      as type 1 diabetes mellitus; the incidence of which follows MS in Finland.
      Population-based case-control studies are needed to identify these factor
      effects. 

PMID- 24324889
TI  - Assessment of a new e-learning system on thorax, trachea, and lung ultrasound.
AB  - Background. Lung ultrasound has become an emerging tool in acute and critical
      care medicine. Combined theoretical and hands-on training has been required to
      teach ultrasound diagnostics. Current computer technology allows for display,
      explanation, and animation of information in a remote-learning environment.
      Objective. Development and assessment of an e-learning program for lung
      ultrasound. Methods. An interactive online tutorial was created. A prospective
      learning success study was conducted with medical students using a multiple
      choice test (Trial A). This e-learning program was used as preparation for a
      certified course followed by an evaluation of trained doctors (Trial B) by linear
      analogue scales. Pretests were compared with postcourse tests and sustainability
      tests as well as a posttest of a one-day custom classroom training. Results. In
      Trial A, during the learning success study (n = 29), the increase of correct
      answers was 11.7 to 17/20 in the post-test and to 16.6/20 in the sustainability
      test (relative change 45.1%, P < 0.0001). E-learning almost equalled scores of
      classroom-based training regarding gain and retention of factual knowledge. In
      Trial B, nineteen participating doctors found a 79.5% increase of knowledge
      (median, 95% CI: 69%; 88%). Conclusion. The basics of lung ultrasound can be
      taught in a highly effective manner using e-learning. 

PMID- 24324890
TI  - Location of sternal fractures as a possible marker for associated injuries.
AB  - Introduction. Sternal fractures often occur together with serious and life
      threatening additional injuries. This retrospective study was designed to assess
      concomitant injuries and develop a correlation between fracture location and the
      severity of injury. Methods. All patients (n = 58) diagnosed with a fracture of
      the sternum by means of a CT scan were analysed with respect to accident
      circumstances, fracture morphology and topography, associated injuries, and
      outcome. Results. Isolated sternal fractures occurred in 9%. In all other
      admissions, concomitant injuries were diagnosed: mainly rip fractures (64%),
      injury to the head (48%), the thoracic spine (38%), lumbar spine (27%), and
      cervical spine (22%). Predominant fracture location was the manubrium sterni. In
      these locations, the observed mean ISS was the highest. They were strongly
      associated with thoracic spine and other chest injuries. Furthermore, the
      incidence of head injuries was significantly higher. ICU admission was
      significantly higher in patients with manubrium sterni fractures. Conclusion.
      Sternal fractures are frequently associated with other injuries. It appears that
      the fracture location can provide important information regarding concomitant
      injuries. In particular, in fractures of manubrium sterni, the need for further
      detailed clinical and radiologic workup is necessary to detect the frequently
      associated injuries and reduce the increased mortality. 

PMID- 24324891
TI  - Intravital microscopic research of microembolization with degradable starch
      microspheres.
AB  - Treatment efficacy in cancer patients using systemically applied cytostatic drugs
      is decreased by cytotoxic side effects, which limits the use of efficient
      dosages. Degradable starch microspheres (DSM) are used to apply drugs into blood
      vessels which supply the target organ leading to drug accumulation in the target
      organ by reduction of the blood flow. The present investigations show that DSM is
      a very effective embolization material leading to effective and enhanced
      accumulation of 5-FU within the liver tumor tissue of experimental induced liver
      cancer in rats. By using intravital microscopy, a rapid deceleration of the blood
      flow into the target organ is observed immediately after application of DSM. The
      microspheres are stepwise degraded in the direction of the systemic blood flow
      and are totally dissolved after 25 minutes. These stepwise processes leave the
      degraded material during the degradation process within the vessels leading to
      temporally reciprocal blood flow via some of the side-arms of the major blood
      vessels. By using DMS in transarterial chemoembolization (TACE), severe adverse
      side effects like postembolization syndrome are rarely observed when compared to
      other embolization materials. The complete degradation of DSM causes only a short
      lasting temporary vascular occlusion, which allows a repeat application of DSM in
      TACE. 

PMID- 24324892
TI  - Influence of cow bone particle size distribution on the mechanical properties of
      cow bone-reinforced polyester composites.
AB  - This work was carried out to investigate the influence of cow bone particle size
      distribution on the mechanical properties of polyester matrix composites in order
      to consider the suitability of the materials as biomaterials. Cow bone was
      procured from an abattoir, washed with water, and sun-dried for 4 weeks after
      which it was crushed with a sledge hammer and was further pulverized with
      laboratory ball mill. Sieve size analysis was carried out on the pulverized bone
      where it was sieved into three different sizes of 75, 106, and 300 MUm sieve
      sizes. Composite materials were developed by casting them into tensile and
      flexural tests moulds using predetermined proportions of 2, 4, 6, and 8%. The
      samples after curing were striped from the moulds and were allowed to be further
      cured at room temperature for 3 weeks before tensile and flexural tests were
      performed on them. Both tensile and flexural strength were highly enhanced by 8
      wt% from 75 MUm while toughness was highly enhanced by 6 and 8 wt% from 300 MUm.
      This shows that fine particles lead to improved strength while coarse particles
      lead to improved toughness. The results show that these materials are
      structurally compatible and are being developed from animal fibre based particle;
      it is expected to also aid the compatibility with the surface conditions as
      biomaterials. 

PMID- 24324893
TI  - Chiral phosphinate degradation by the fusarium species: scope and limitation of
      the process.
AB  - Biodegradable capacities of fungal strains of Fusarium oxysporum (DSMZ 2018) and
      Fusarium culmorum (DSMZ 1094) were tested towards racemic mixture of chiral 2
      hydroxy-2-(ethoxyphenylphosphinyl) acetic acid-a compound with two stereogenic
      centres. The effectiveness of decomposition was dependent on external factors
      such as temperature and time of the process. Optimal conditions of complete
      mineralization were established. Both Fusarium species were able to biodegrade
      every isomer of tested compound at 30 degrees C, but F. culmorum required 10 days
      and F. oxysporum 11 days to accomplish the process, which was continuously
      monitored using the (31)P NMR technique. 

PMID- 24324894
TI  - Sex hormone receptor repertoire in breast cancer.
AB  - Classification of breast cancer as endocrine sensitive, hormone dependent, or
      estrogen receptor (ER) positive refers singularly to ER alpha . One of the oldest
      recognized tumor targets, disruption of ER alpha -mediated signaling, is believed
      to be the mechanistic mode of action for all hormonal interventions used in
      treating this disease. Whereas ER alpha is widely accepted as the single most
      important predictive factor (for response to endocrine therapy), the presence of
      the receptor in tumor cells is also of prognostic value. Even though the clinical
      relevance of the two other sex hormone receptors, namely, ER beta and the
      androgen receptor remains unclear, two discordant phenomena observed in hormone
      dependent breast cancers could be causally related to ER beta -mediated effects
      and androgenic actions. Nonetheless, our understanding of regulatory molecules
      and resistance mechanisms remains incomplete, further compromising our ability to
      develop novel therapeutic strategies that could improve disease outcomes. This
      review focuses on the receptor-mediated actions of the sex hormones in breast
      cancer. 

PMID- 24324895
TI  - Impact of pretransplant hepatic encephalopathy on liver posttransplantation
      outcomes.
AB  - Patients with cirrhosis commonly experience hepatic encephalopathy (HE), a
      condition associated with alterations in behavior, cognitive function,
      consciousness, and neuromuscular function of varying severity. HE occurring
      before liver transplant can have a substantial negative impact on posttransplant
      outcomes, and preoperative history of HE may be a predictor of posttransplant
      neurologic complications. Even with resolution of previous episodes of overt or
      minimal HE, some patients continue to experience cognitive deficits after
      transplant. Because HE is one of the most frequent pretransplant complications,
      improving patient HE status before transplant may improve outcomes. Current
      pharmacologic therapies for HE, whether for the treatment of minimal or overt HE
      or for prevention of HE relapse, are primarily directed at reducing cerebral
      exposure to systemic levels of gut-derived toxins (e.g., ammonia). The current
      mainstays of HE therapy are nonabsorbable disaccharides and antibiotics. The
      various impacts of adverse effects (such as diarrhea, abdominal distention, and
      dehydration) on patient's health and nutritional status should be taken into
      consideration when deciding the most appropriate HE management strategy in
      patients awaiting liver transplant. This paper reviews the potential consequences
      of pretransplant HE on posttransplant outcomes and therapeutic strategies for the
      pretransplant management of HE. 

PMID- 24324896
TI  - Development of dengue infection severity score.
AB  - Objectives. To develop a simple scoring system to predict dengue infection
      severity based on patient characteristics and routine clinical profiles. Methods.
      Retrospective data of children with dengue infection from 3 general hospitals in
      Thailand were reviewed. Dengue infection was categorized into 3 severity levels:
      dengue infection (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome
      (DSS). Coefficients of significant predictors of disease severity under ordinal
      regression analysis were transformed into item scores. Total scores were used to
      classify patients into 3 severity levels. Results. Significant clinical
      predictors of dengue infection severity were age >6 years, hepatomegaly,
      hematocrit >=40%, systolic pressure <90 mmHg, white cell count >5000 / MU L, and
      platelet <=50000 / MU L. The derived total scores, which ranged from 0 to 18,
      classified patients into 3 severity levels: DF (scores <2.5, n = 451, 58.1%), DHF
      (scores 2.5-11.5, n = 276, 35.5%), and DSS (scores >11.5, n = 50, 6.4%). The
      derived score correctly classified patients into their original severity levels
      in 60.7%. An under-estimation of 25.7% and an over-estimation of 13.5% were
      clinically acceptable. Conclusions. The derived dengue infection severity score
      classified patients into DF, DHF, or DSS, correctly into their original severity
      levels. Validation of the score should be reconfirmed before application of
      routine practice. 

PMID- 24324898
TI  - Quality of scar after total thyroidectomy: a single blinded randomized trial
      comparing octyl-cyanoacrylate and subcuticular absorbable suture.
AB  - Objective. To compare the quality of resulting scar at 6 weeks after total
      thyroidectomy with the use of the tissue adhesive octyl-cyanoacrylate or
      subcuticular absorbable suture for the closure of cervicotomy. Material and
      Methods. There are 50 patients undergoing a cervicotomy for total thyroidectomy.
      Twenty-five patients were randomly assigned to closure with tissue adhesive and
      25 with subcuticular absorbable suture. At week 6 the scar was evaluated by
      blinded assessors with the Italian version of POSAS questionnaire, a validated
      wound scale composed of an observer's and a patient's subscale. Results.
      Assessment of scar appearance showed a statistically significant difference (p =
      0. 038) in favor of subcuticular suture with respect to tissue adhesive on
      observer's assessment. The difference on patients' self-assessment was not
      significant. A multivariate analysis of six qualitative features of scars showed
      a significant influence on assessment for hyperpigmentation and relief of scar.
      The Italian version of POSAS proved to be reliable. Conclusion. Though tissue
      adhesive represents a valid method of skin closure, subcuticular absorbable
      suture provides a better aesthetic outcome in small cervical incisions in the
      early phase after thyroid surgery. 

PMID- 24324897
TI  - Complementary therapies in allergic rhinitis.
AB  - Objective. To determine the prevalence of herbal treatment of allergic rhinitis.
      Methods. In this prospective study, patients who were diagnosed with perennial
      allergic rhinitis were questioned about their use of natural products/herbal
      therapies for their symptoms. Results. In total, 230 patients were enrolled.
      Overall, 37.3% of the patients stated that they had used natural products/herbal
      therapies at least once. Women were more likely than men to use herbal
      supplements (38.3% versus 32.4%). Ten different types of herbal supplements were
      identified, with stinging nettle (Urtica dioicath), black elderberry (Sambucus
      nigra), and Spirulina being the most common (12.6%, 6.1%, and 5.7%, resp.).
      Conclusion. This study found a high prevalence of herbal treatment usage for the
      relief of allergic rhinitis symptoms in Turkey. The herbal products identified in
      this study and in the literature are discussed. 

PMID- 24324899
TI  - Induction of maturogenesis by partial pulpotomy: 1 year follow-up.
AB  - In cariously exposed immature permanent teeth, the treatment choice is
      controversial in pediatric dentistry. Radical root canal treatment usually
      appears to be the solution for these teeth. Even partial pulpotomy is a vital
      treatment for traumatically exposed immature permanent teeth; extending the
      borders of indication towards cariously exposed immature permanent teeth with
      reversible pulpitis may abolish the necessity of pulpectomy. This article
      describes the partial pulpotomy of a cariously affected immature permanent teeth
      and the follow-up for 1 year. A healthy 11-year-old male patient was referred to
      Gazi University Faculty of Dentistry Department of Pediatric Dentistry. The
      patient had reversible pulpitis symptoms on teeth numbered 45. At radiographic
      examination, immature apex and deep caries lesion were observed and partial
      pulpotomy was performed by using calcium hydroxide to maintain vitality of the
      pulp and allow continued development of root dentin expecting the root will
      attain full maturity. Clinical and radiographic follow-up demonstrated a vital
      pulp besides not only closure of the apex (apexogenesis), but also physiologic
      root development (maturogenesis) after 1 year. Partial pulpotomy is an optional
      treatment for cariously exposed immature permanent teeth for preserving vitality
      and physiological root development. 

PMID- 24324900
TI  - E. coli Meningitis Presenting in a Patient with Disseminated Strongyloides
      stercoralis.
AB  - Introduction. Spontaneous Escherichia coli meningitis is an infrequent condition
      in adults and is associated with some predisposing factors, including severe
      Strongyloides stercoralis (SS) infections. Case Presentation. A 43-year-old
      Hispanic man, with history of travelling to the jungle regions of Peru and Brazil
      two decades ago, and who received prednisone due to Bell's palsy for three weeks
      before admission, presented to the Emergency Department with diarrhea, fever, and
      hematochezia. A week after admission he developed drowsiness, meningeal signs,
      abdominal distension, and constipation. A cerebrospinal fluid culture showed
      extended spectrum beta -lactamase producing E. coli. A colonoscopy was performed
      and showed pancolitis. Three days after the procedure the patient became unstable
      and developed peritoneal signs. He underwent a laparotomy, which ended up in a
      total colectomy and partial proctectomy due to toxic megacolon. Three days later
      the patient died in the intensive care unit due to septic shock. Autopsy was
      performed and microscopic examination revealed the presence of multiple
      Strongyloides larvae throughout the body. Conclusion. Strongyloides stercoralis
      infection should be excluded in adults with spontaneous E. coli meningitis,
      especially, if gastrointestinal symptoms and history of travelling to an endemic
      area are present. Even with a proper diagnosis and management, disseminated
      strongyloidiasis has a poor prognosis. 

PMID- 24324901
TI  - Intracranial hypotension with multiple complications: an unusual case report.
AB  - Background. Undiagnosed intracranial hypotension can result in several
      complications including subdural hematoma (SDH), subarachnoid hemorrhage (SAH),
      dural venous sinuses thrombosis (CVT), cranial nerve palsies, and stupor
      resulting from sagging of the brain. It is rare to see all the complications in
      one patient. Furthermore, imaging of the brain vasculature may reveal incidental
      asymptomatic small aneurysms. Given the combination of these imaging findings and
      a severe headache, the patients are often confused to have a primary subarachnoid
      hemorrhage. Case Report. We present a patient with spontaneous intracranial
      hypotension (SIH) who had an incidental ophthalmic artery aneurysm on MR imaging,
      and this presentation led to coiling of the aneurysm. The key aspect in the
      history "postural headaches" was missed, and this led to life threatening
      complications and unnecessary interventions. Revisiting the history and
      significant improvement in symptoms following an epidural blood patch resulted in
      the diagnosis of SIH. Conclusion. We strongly emphasize that appropriate history
      taking is the key in the diagnosis of SIH and providing timely treatment with an
      epidural blood patch could prevent potentially life threatening complications. 

PMID- 24324902
TI  - Neurolymphomatosis of Brachial Plexus in Patients with Non-Hodgkin's Lymphoma.
AB  - Neurolymphomatosis (NL) is a rare clinical disease where neoplastic cells invade
      the cranial nerves and peripheral nerve roots, plexus, or other nerves in
      patients with hematologic malignancy. Most NL cases are caused by B-cell non
      Hodgkin's lymphoma (NHL). Diagnosis can be made by imaging with positron emission
      tomography (PET) and magnetic resonance imaging (MRI). We experienced two cases
      of NL involving the brachial plexus in patients with NHL. One patient, who had
      NHL with central nervous system (CNS) involvement, experienced complete remission
      after 8 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,
      and prednisone) chemotherapy but relapsed into NL of the brachial plexus 5 months
      later. The other patient, who suffered from primary central nervous system
      lymphoma (PCNSL), had been undergoing chemoradiotherapy but progressed to NL of
      the brachial plexus. 

PMID- 24324903
TI  - Aggressive pseudomyxoma peritonei: a case report with an unusual clinical
      presentation.
AB  - Introduction. Pseudomyxoma peritonei (PMP) is an uncommon surgical entity. We
      report a case of aggressive disease with an unusual clinical presentation and we
      analyze current data on diagnosis and management of PMP. Case Presentation. A 71
      year-old male patient presented with intermittent diarrhea and loss of appetite
      during the last two months, without any other classic symptoms of PMP. The
      clinical examination was misleading due to patient's obesity. The radiological
      evaluation revealed ascites of the abdomen and possible mucocele of the appendix,
      whereas the laboratory exams showed high values of specific tumour markers. The
      patient underwent an exploratory laparotomy for definite diagnosis. Biopsies and
      immunohistochemical examination confirmed the diagnosis of an aggressive and
      extended peritoneal mucinous carcinomatosis (PMCA). The patient was programmed
      for adjuvant systematic chemotherapy, which was not completed due to progression
      of the disease. Conclusions. Progressed PMP can present with unspecific symptoms
      that mislead diagnosis. Cytoreductive surgery in combination with systematic
      chemotherapy could be appropriate for aggressive PMCA, even with an unfavourable
      prognosis. 

PMID- 24324904
TI  - Unusual metastatic patterns of invasive lobular carcinoma of the breast.
AB  - Invasive lobular carcinoma of the breast has similar patterns of metastatic
      disease when compared to invasive ductal carcinoma; however, lobular carcinoma
      metastasizes to unusual sites more frequently. We present a 65-year-old female
      with a history of invasive lobular breast carcinoma (T3N3M0) treated with
      modified radical mastectomy and aromatase-inhibitor therapy who underwent a
      surveillance PET scan, which showed possible sigmoid cancer. Colonoscopy with
      biopsy revealed a 3 cm sigmoid adenocarcinoma. The patient underwent a lower
      anterior resection. Pathology showed an ulcerated, invasive moderately
      differentiated adenocarcinoma extending into but not through the muscularis
      propria. However, six of seventeen paracolonic lymph nodes were positive for
      metastatic breast carcinoma (ER+/PR+), consistent with her lobular primary breast
      carcinoma; there was no evidence of metastatic colon cancer. This case highlights
      the unusual metastatic patterns of lobular carcinoma. 

PMID- 24324905
TI  - Spinal exostosis in a boy with multiple hereditary exostoses.
AB  - We report on a 13-year-old boy who presented with multiple hereditary exostosis
      and had development of back pain, associated with neurological deficits, and was
      found to have exostoses in the spinal canal. Spine radiograph showed a
      cauliflower-like abnormality of multiple exostoses of the posterior arch
      (pedicle) of the thoracic vertebrae (T3-5). Reformatted CT scanning revealed the
      simultaneous development of intra- and extraspinal osteochondromatosis of T3-5.
      The spinal cord was compressed by the intraspinal exostosis. Our patient was
      surgically treated for intraspinal exostoses and showed cessation of neurological
      deficits. We report what might be a rare association of spinal cord compression
      in a patient with multiple hereditary exostoses. 

PMID- 24324906
TI  - Localized pigmented villonodular synovitis of the hip: sudden-onset pain caused
      by torsion of the tumor pedicle.
AB  - Pigmented villonodular synovitis is a rare, benign, but potentially locally
      aggressive disease that should be considered in younger patients who present with
      monoarticular joint symptoms and pathology. We present the case of a 33-year-old
      woman with a mass arising from her right hip joint that was examined using a
      multimodal radiological approach. Because her clinical presentation mimicked that
      of synovial osteochondromatosis of the hip, surgical dislocation was performed.
      Histopathological examination of the resected specimen confirmed the diagnosis of
      localized pigmented villonodular synovitis, with the mass consisting of
      proliferation of fibrohistiocytic cells, abundant hemosiderin, foamy histiocytes,
      and occasional giant cells. Because of the presence of tumor necrosis, we
      hypothesize that torsion of the tumor pedicle was the cause of acute
      presentation. 

PMID- 24324907
TI  - A rare component of psammomatous meningioma in a testicular teratoma.
AB  - We report a case of a psammomatous variant of meningioma arising in a pure and
      mature testicular teratoma. At immunohistochemistry, the meningiomatous component
      showed epithelial membrane antigen, S100 protein, and vimentin positive. Benign
      neoplasms arising in testicular teratomas are extremely rare. To our knowledge,
      we have not found any such report of psammomatous variant of meningioma in a
      testicular teratoma and any meningioma arising in a pure and mature testicular
      teratoma. This is a unique phenomenon. 

PMID- 24324908
TI  - A Case of Mild Encephalopathy with a Reversible Splenial Lesion Associated with
      G5P[6]Rotavirus Infection.
AB  - We report a case of mild encephalopathy with a reversible splenial lesion (MERS)
      associated with acute gastroenteritis caused by rotavirus (RV) infection. The
      patient (male, 4 years and 3 months old) was admitted to our hospital for
      diarrhea and afebrile seizures. Head MRI revealed a hyperintense signal in the
      splenium of the corpus callosum on DWI and a hypointense signal on the ADC-map.
      After awakening from sedation, the patient's disturbance of consciousness
      improved. On day 5 after admission of the illness, the patient was discharged
      from the hospital in a good condition. Electroencephalography on day 2 after
      admission was normal. On day 8 of admission, head MRI revealed that the splenial
      lesion had disappeared. RV antigen-positive stools suggested that RV had caused
      MERS. This RV genotype was considered to be G5P[6]; it may have spread to humans
      as a strain reassortment through substitution of porcine RV into human RV gene
      segments. This extremely rare genotype was detected first in Japan and is not
      covered by existing vaccines; this is the first sample isolated from
      encephalopathy patients. Few reports have investigated RV genotypes in
      encephalopathy; we believe that this case is valuable for studying the
      relationship between genotypes and clinical symptoms. 

PMID- 24324909
TI  - Psoriasiform drug eruption associated with sodium valproate.
AB  - As psoriasis is a common skin disorder, knowledge of the factors that may induce,
      trigger, or exacerbate the disease is of primary importance in clinical practice.
      Drug intake is a major concern in this respect, as new drugs are constantly being
      added to the list of factors that may influence the course of the disease. We
      report a patient with a psoriasiform drug eruption associated with the use of
      sodium valproate. Physicians should be aware of this type of reaction. Early
      detection of these cases has practical importance since the identification and
      elimination of the causative drug are essential for therapy success. 

PMID- 24324910
TI  - Transition from hepatopulmonary syndrome to portopulmonary hypertension: a case
      series of 3 patients.
AB  - Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are the
      two major pulmonary vascular complications of liver disease. While HPS is
      characterized by low pulmonary vascular resistance, PPHTN is defined by the
      presence of elevated pulmonary vascular resistance. Given these seemingly
      opposing pathophysiologic mechanisms, these conditions were traditionally felt to
      be mutually exclusive. In this series, we present three patients with severe
      hepatopulmonary syndrome who had spontaneous resolution of their HPS with the
      subsequent development of PPHTN. To our knowledge, this is the largest case
      series presented of this phenomenon in nontransplanted patients. One proposed
      mechanism for the occurrence of this phenomenon involves dysregulation of the
      same vascular signaling pathway, which may lead to both pulmonary vascular
      dilatations and pulmonary arterial remodeling in the same patient. Another theory
      involves the possible differential binding of endothelin-1, a vasoactive
      signaling peptide that induces vasoconstriction when bound to receptor A and
      vasodilation when bound to receptor B. Although the mechanisms for this
      phenomenon remain unclear, it is important to be vigilant of this phenomenon as
      it may change the patient's overall treatment plan, especially in regard to
      appropriateness and timing of liver transplant. 

PMID- 24324911
TI  - The efficacy and safety of rituximab in a patient with rheumatoid spondylitis.
AB  - Rheumatoid arthritis (RA) is considered as a connective tissue disease while
      ankylosing spondylitis (AS) is a prototype of spondyloarthritis. These diseases
      are seen concomitantly only very rarely. Also, rituximab has proven efficacy in
      the treatment of RA while its role in the treatment of AS is unclear. In this
      presentation, the concomitant presence of RA and AS in a 43-year-old male patient
      as well as the efficacy and safety of rituximab is discussed. Rituximab was given
      due to lack of response to treatment with anti-TNF-alpha. Evaluations made at the
      6th and 12th months of treatment showed complete response for RA and partial
      response for AS. 

PMID- 24324912
TI  - Acute idiopathic scrotal edema.
AB  - We report a case of acute idiopathic scrotal edema (AISE) in a 4-year-old boy who
      presented with acute scrotal pain and erythema. The clinical features, ultrasound
      appearance, and natural history of this rare diagnosis are reviewed. In this
      report, we highlight the importance of good ultrasound technique in
      differentiating the etiology of the acute scrotum and demonstrate the color
      Doppler "Fountain Sign" that is highly suggestive of AISE. 

PMID- 24324913
TI  - Acute thoracic aortic dissection (stanford type B) complicated with acute renal
      failure.
AB  - We report a recent case and review some literatures of acute aortic dissection
      (AAD) Stanford type B complicated with late onset of acute renal failure. The
      patient underwent preoperational peritoneal dialysis followed by thoracic
      endovascular aortic repair (TEVAR) and was fully recovered and discharged soon
      after surgery. We conclude that an AAD case is difficult to achieve a timely
      diagnosis, but with attention to systemic symptoms and dedication thorough
      treatment plan, a full recovery and positive prognosis are expected. 

PMID- 24324914
TI  - A giant coronary artery aneurysm with coronary arteriovenous fistula in
      asymptomatic elderly patient.
AB  - Coronary Arteriovenous Fistula (CAF) is a rare defect that occurs in 0.1-0.2% of
      patients undergoing coronary angiography; Coronary Artery Aneurism (CAA) also
      occurs in approximately 15-19% of patients with CAF. It is usually congenital,
      but in rare occasions it occurs after chest trauma, cardiac surgery, or coronary
      interventions. The case described is that of a 72-year-old woman, without
      previous history of cardiovascular disease, who presented a huge cardiac mass. A
      multimodal approach was necessary to diagnose a giant CAA with CAF responsible
      for compression and displacement of cardiac structures. Due to likely
      congenitally origin of the lesion and the absence of symptoms correlated to the
      CAA and to the CAF we decided to avoid invasive interventions and to treat the
      patient with medical therapy. 

PMID- 24324915
TI  - Cost Effectiveness of TNF-alpha Inhibitors in Rheumatoid Arthritis.
AB  - Background. TNF-alpha inhibitors have shown to be effective in reducing disease
      activity and improving the quality of life. Due to the high costs associated with
      acquisition of this treatment, this study was undertaken to evaluate the ICER of
      TNF-alpha antagonists (etanercept, adalimumab, and infliximab) in improving the
      quality of life. Methods. The HAQ and SF-36 were administered at phases 1, 2, and
      3, in order to assess the improvement in the QOL. Suppression of disease activity
      was assessed through the DAS-28. Results. Statistically significant improvements
      (P < 0.05) were noted for the SF-36 and HAQ after 3 months and for the DAS-28
      after 6 months of TNF-alpha inhibitor therapy. The mean ICER per 10% improvement
      in the HAQ, DAS-28, and SF-6D were ?1976.5, ?2086.5, and ?2316.4, respectively,
      following 6 months of TNF-alpha intervention. Most favorable ICERs were reported
      from a patient who had to undergo surgical intervention whilst on DMARD therapy.
      Conclusion. Significant improvement was observed in patients' quality of life,
      after a short timeframe of 6 months. Such data is useful information in the light
      of convincing policy makers, in terms of providing access to the medications to
      individual patients on national health service schemes. 

PMID- 24324916
TI  - In Vitro Antioxidative Evaluation of alpha- and beta-Carotene, Isolated from
      Crude Palm Oil.
AB  - The present work describes the isolation of alpha - and beta -carotene from crude
      palm oil and their antioxidant potential in an in vitro model. Pure product was
      isolated by the method adopted. Antioxidant activities of the isolated alpha -
      and beta -carotene were analyzed in five different concentrations of 0.001,
      0.005, 0.01, 0.05, and 0.1% (w/v). From the several assays conducted, an
      observation was made that the antioxidant activity of the product shifted between
      antioxidant and prooxidant effects depending on the concentration and the system
      analyzed. The metal chelation, DPPH radical scavenging, and superoxide scavenging
      activities showed almost similar results in terms of high activity at lowest
      concentrations. ABTS-scavenging activity was displayed only by a particular
      antioxidant concentration of 0.1%. Lipid peroxidation assay pronounced the
      activity of 0.1% antioxidant in inhibiting oxidation of sensitive bioactive
      lipids. In vitro antidenaturation test again specified the efficacy of low
      concentrations in preventing protein denaturation. Through this study a definite
      dosage formulation for consumption of carotenoids is being proposed which will
      enhance health promotion and prevent chronic diseases when taken as fortified
      foods or dietary supplements. 

PMID- 24324917
TI  - Combinatorial Effect of Metformin and Lovastatin Impedes T-cell Autoimmunity and
      Neurodegeneration in Experimental Autoimmune Encephalomyelitis.
AB  - Multiple Sclerosis (MS) is an incurable central nervous system (CNS)
      demyelinating disease affecting several million people worldwide. Due to the
      multifactorial and complex pathology of MS, FDA approved drugs often show limited
      efficacy inpatients. We earlier documented that both lovastatin (cholesterol
      lowering drug) and metformin (anti-diabetic drug) attenuate experimental
      autoimmune encephalomyelitis (EAE), a widely used model of MS via different
      mechanisms of action. Since combination therapy of two or more agents has
      advantage over monotherapy, we here assessed the therapeutic efficacy of
      metformin and lovastatin combination in EAE. We found that suboptimal doses of
      these drugs in combination had additive effect to attenuate established EAE in
      treated animals than their individual treatments. Histological,
      immunohistochemistry and western blotting analyses revealed that the observed
      demyelination and axonal loss as evident from reduced levels of myelin and
      neurofilament proteins in the spinal cords of EAE animals were attenuated by
      treatment with these drugs in combination. Accordingly, the observed infiltration
      of myelin reactive T cells (CD4 and CD8) and macrophages (CD68) as well as the
      increased expression of their signatory cytokines in the spinal cords of EAE
      animals were attenuated by this regimen as revealed by enzyme-linked immune
      sorbent assay and real-time PCR analyses. In the periphery, this regimen biased
      the class of elicited anti-myelin basic protein immunoglobulins from IgG2a to
      IgG1 and IgG2b, suggesting a Th1 to Th2 shift which was further supported by the
      increased expression of their signatory cytokines in EAE animals. Taken together,
      these data imply that metformin and lovastatin combination attenuates T-cell
      autoimmunity and neurodegeneration in treated EAE animals thereby suggesting that
      the oral administration of these FDA approved drugs in combination has potential
      to limit MS pathogenesis.

PMID- 24324918
TI  - The Motivations and Experiences of Young Women in a Microbicide Trial in the USA
      and Puerto Rico.
AB  - Young women are an important target group in microbicide research, yet little is
      known about why they participate and stay in microbicide trials. Our study
      examined motivations for participating in a Phase I microbicide trial among 61
      women ages 18 - 24 years in the continental USA and Puerto Rico. We also examined
      their perspectives on study participation. Participants underwent a semi
      structured in-depth interview in which they were asked about factors that
      motivated enrollment and their experiences while participating. They also
      completed a Web-based Computer Assisted Self Interview in which they were asked
      to rate study burden (1 = low to 4 = high). Factors that motivated enrollment
      were altruism (29%), compensation (17%), a combination of altruism and
      compensation (37%) and free medical exams (17%). Factors that encouraged
      participants to stay in the study were study staff (95%), confirmation of good
      health (41%), and the opportunity to learn about their bodies (17%). Mean ratings
      of study burden ranged from 1.83 (having to travel to site) to 2.41 (colposcopy),
      indicating that participants were not highly bothered by visits or procedures.
      Although Phase I trials require invasive procedures, participants were not highly
      bothered by them and recognized them as necessary. Good relationships with staff
      and clear information about how procedures contribute to study goals may
      encourage participants to remain in trials. Young women may be motivated to enter
      microbicide trials by stressing the role they will play in discovering better HIV
      prevention methods and highlighting the comprehensive preventive exams they will
      receive.

PMID- 24324919
TI  - Resolving the spatial relationship between intracellular components by dual color
      super resolution optical fluctuations imaging (SOFI).
AB  - BACKGROUND: Multi-color super-resolution (SR) imaging microscopy techniques can
      resolve ultrastructura relationships between- and provide co-localization
      information of- different proteins inside the cell or even within organelles at a
      higher resolution than afforded by conventional diffraction-limited imaging.
      While still very challenging, important SR colocalization results have been
      reported in recent years using STED, PALM and STORM techniques. RESULTS: In this
      work, we demonstrate dual-color Super Resolution Optical Fluctuations Imaging
      (SOFI) using a standard far-field fluorescence microscope and different color
      blinking quantum dots. We define the spatial relationship between hDcp1a, a
      processing body (P-body, PB) protein, and the tubulin cytoskeletal network. Our
      finding could open up new perspectives on the role of the cytoskeleton in PB
      formation and assembly. Further insights into PB internal organization are also
      reported and discussed. CONCLUSIONS: Our results demonstrate the suitability and
      facile use of multi-color SOFI for the investigation of intracellular
      ultrastructures.

PMID- 24324920
TI  - The effectiveness of an abbreviated training program for health workers in breast
      cancer awareness: innovative strategies for resource constrained environments.
AB  - BACKGROUND: Breast cancer is characterized by late presentation and significant
      morbidity and mortality in developing countries. Breast screening aids in early
      detection of breast cancer. Nurses are uniquely placed to provide advocacy and
      screening in a resource limited environment. OBJECTIVES: To assess the
      effectiveness of an abbreviated training program in breast cancer awareness on
      nurses at a tertiary hospital, in a resource constrained environment. METHODS:
      Using a statistical tool, the Solomon Model, 79 nurses were identified and
      divided into experimental and control groups. An abbreviated training
      intervention in breast cancer awareness was administered to the experimental
      group. Pre and post test questionnaires and objective structured clinical
      examinations were used to determine nurses' knowledge and practice skills before
      and after the abbreviated training intervention. RESULTS: Initial scores of
      knowledge and practice skills related to clinical breast examination were low:
      Mean knowledge scores of 18 out of 25 [72%] and mean practice scores of 12.5 out
      of 30 [41.6%]. Significant improvement was observed following the abbreviated
      training intervention in both knowledge and practice skills. Knowledge scores of
      22 out of 25 [88%, p = < 0.001] and practice scores of 26 out of 30 [86.6%,
      p=0.003]. Trained nurses were able to improve their knowledge of breast cancer
      from fair to good knowledge. CONCLUSION: There is need to increase breast
      awareness, both in terms of knowledge and practice skills, in nurses as a means
      of improving awareness among the general population and early detection of breast
      cancer. An abbreviated training in breast cancer awareness can improve these
      skills in nurses.

PMID- 24324921
TI  - 5-Aminolevulinic acid enhances cancer radiotherapy in a mouse tumor model.
AB  - 5-Aminolevulinic acid (ALA) is a photosensitizer used in photodynamic therapy
      (PDT) because it causes preferential accumulation of protoporphyrin IX (PpIX) in
      tumor cells, where it forms singlet oxygen upon light irradiation and kills the
      tumor cells. Our previous study demonstrated that PpIX enhances generation of
      reactive oxygen species by physicochemical interaction with X-rays. We
      investigated the effect of ALA administration with X-ray irradiation of mouse B16
      BL6 melanoma cells in vitro and in vivo. ALA facilitates PpIX accumulation in
      tumor cells and enhances ROS generation in vitro. Tumor suppression significantly
      improved in animals treated with fractionated doses of radiation (3 Gy * 10;
      total, 30 Gy) with local administration of 50 mg/kg ALA at 24 h prior to
      fractional irradiation. These results suggest ALA may improve the efficacy of
      cancer radiotherapy by acting as a radiomediator. 

PMID- 24324922
TI  - Analysis of 10 km swimming performance of elite male and female open-water
      swimmers.
AB  - This study investigated trends in performance and sex difference in swimming
      speed of elite open-water swimmers at FINA 10 km competitions (i.e. World Cup
      races, European Championships, World Championships and Olympic Games). Swimming
      speed and sex difference in swimming speed of the fastest and the top ten women
      and men per event competing at 10 km open-water races between 2008 and 2012 were
      analysed using single and multi-level regression analyses. A total of 2,591
      swimmers (i.e. 1,120 women and 1,471 men) finished 47 races. Swimming speed of
      the fastest women (1.35 +/- 0.9 m/s) and men (1.45 +/- 0.10 m/s) showed no
      changes across years. The mean sex difference in swimming speed for the fastest
      swimmers was 6.8 +/- 2.5%. Swimming speed of the top ten female swimmers per
      event was 1.34 +/- 0.09 m/s and remained stable across the years. The top ten
      male swimmers per event showed a significant decrease in swimming speed over
      time, even though swimming speed in the first race (i.e. January 2008, 1.40 +/-
      0.0 m/s) was slower than the swimming speed in the last race (i.e. October 2012,
      1.50 +/- 0.0 m/s) (P < 0.05). To summarize, swimming performances remained stable
      for the fastest elite open-water swimmers at 10 km FINA competitions between 2008
      and 2012, while performances of the top ten men tended to decrease. The sex
      difference in swimming speed in elite ultra-swimmers (~7%) appeared smaller
      compared to other ultra-distance disciplines such as running. Further studies
      should examine how body shape and physiology of elite open-water ultra-distance
      swimmers influence performances. 

PMID- 24324923
TI  - Bacterial community composition shifts in the gut of Periplaneta americana fed on
      different lignocellulosic materials.
AB  - ABSTRACT: Cockroaches are insects that can accommodate diets of different
      composition, including lignocellulosic materials. Digestion of these compounds is
      achieved by the insect's own enzymes and also by enzymes produced by gut
      symbionts. The presence of different and modular bacterial phyla on the cockroach
      gut tract suggests that this insect could be an interesting model to study the
      organization of gut bacterial communities associated with the digestion of
      different lignocellulosic diets. Thus, changes in the diversity of gut associated
      bacterial communities of insects exposed to such diets could give useful insights
      on how to improve hemicellulose and cellulose breakdown systems. In this work,
      through sequence analysis of 16S rRNA clone libraries, we compared the
      phylogenetic diversity and composition of gut associated bacteria in the
      cockroach Periplaneta americana collected in the wild-types or kept on two
      different diets: sugarcane bagasse and crystalline cellulose. These high fiber
      diets favor the predominance of some bacterial phyla, such as Firmicutes, when
      compared to wild-types cockroaches. Our data show a high bacterial diversity in
      P. americana gut, with communities composed mostly by the phyla Bacteroidetes,
      Firmicutes, Proteobacteria and Synergistetes. Our data show that the composition
      and diversity of gut bacterial communities could be modulated by diet
      composition. The increased presence of Firmicutes in sugarcane bagasse and
      crystalline cellulose-fed animals suggests that these bacteria are strongly
      involved in lignocellulose digestion in cockroach guts. BACKGROUND: Cockroaches
      are omnivorous animals that can incorporate in their diets food of different
      composition, including lignocellulosic materials. Digestion of these compounds is
      achieved by the insect's own enzymes and also by enzymes produced by gut
      symbiont. However, the influence of diet with different fiber contents on gut
      bacterial communities and how this affects the digestion of cockroaches is still
      unclear. The presence of some bacterial phyla on gut tract suggests that
      cockroaches could be an interesting model to study the organization of gut
      bacterial communities during digestion of different lignocellulosic diets.
      Knowledge about the changes in diversity of gut associated bacterial communities
      of insects exposed to such diets could give interesting insights on how to
      improve hemicellulose and cellulose breakdown systems. METHODOLOGY/PRINCIPAL
      FINDINGS: We compared the phylogenetic diversity and composition of gut
      associated bacteria in the cockroach P. americana caught on the wild or kept on
      two different diets: sugarcane bagasse and crystalline cellulose. For this
      purpose we constructed bacterial 16S rRNA gene libraries which showed that a diet
      rich in cellulose and sugarcane bagasse favors the predominance of some bacterial
      phyla, more remarkably Firmicutes, when compared to wild cockroaches. Rarefaction
      analysis, LIBSHUFF and UniFrac PCA comparisons showed that gene libraries of wild
      insects were the most diverse, followed by sugarcane bagasse fed and then
      cellulose fed animals. It is also noteworthy that cellulose and sugarcane bagasse
      gene libraries resemble each other. CONCLUSION/SIGNIFICANCE: Our data show a high
      bacterial diversity in P. americana gut, with communities composed mostly by the
      phyla Bacteroidetes, Firmicutes, Proteobacteria and Synergistetes. The
      composition and diversity of gut bacterial communities could be modulated by font
      of diet composition. The increased presence of Firmicutes in sugarcane bagasse
      and crystalline cellulose-fed animals suggests that these bacteria are strongly
      involved in lignocellulose digestion in cockroach guts.

PMID- 24324924
TI  - The cardiovascular system and the biochemistry of grafts used in heart surgery.
AB  - Blood is pumped into the cardiac muscle through arteries called the coronary
      arteries. Over time, the accumulation of cholesterol, coagulation factors, and
      cells on the walls of these arteries causes the walls to thicken and lose their
      elasticity, resulting in the development of atherosclerosis. When the blood
      supply of the heart is diminished by atherosclerosis, it can be restored by
      bypass surgery, in which atherosclerosis-free vein and/or artery grafts taken
      from another area of the body are used to replace the atherosclerotic vessels.
      These biological grafts used in surgery differ in biochemical composition and
      long-term patency. Although the great saphenous vein (GSV) has been the most
      popular graft material in revascularization for years, it has recently been
      superseded by the internal mammarian artery (IMA), which has a lower incidence of
      recurrence of atherosclerosis. The aim of the present review is briefly to
      address the structure of the cardiovascular system and blood vessels, and then,
      in the light recent data, to present the biochemical compositions and individual
      advantages of the graft materials used to restore an impaired blood supply to the
      heart. 

PMID- 24324925
TI  - Therapeutic effect of dienogest on adenosarcoma arising from endometriosis: a
      case report.
AB  - Dienogest is a novel synthesized progestin used for treatment of endometriosis.
      This is the first case report describing a therapeutic effect of dienogest on a
      gynecologic malignancy. The patient was a 44-year-old woman with advanced
      adenosarcoma arising from the endometriosis in the rectovaginal space and
      infiltrating the left pelvic wall, left ureter, rectum and vagina. The residual
      tumor after tumor debulking surgery was resistant to both chemotherapy and
      radiotherapy. Dienogest was used as a substitute for medroxyprogesterone acetate
      because of the presence of deep vein thrombosis. Based on the RECIST criteria,
      partial response was obtained with oral dienogest therapy at six months and the
      serum CA125 level also decreased from 70 U/ml to 16 U/ml. The tumor remained
      stable up to 21 months. Thromboembolism or other adverse effects did not occur
      during the dienogest therapy. Dienogest may be useful for the treatment of
      adenosarcoma arising from endometriosis. 

PMID- 24324926
TI  - Identifying influential metrics in the combined metrics approach of fault
      prediction.
AB  - Fault prediction is a pre-eminent area of empirical software engineering which
      has witnessed a huge surge over the last couple of decades. In the development of
      a fault prediction model, combination of metrics results in better explanatory
      power of the model. Since the metrics used in combination are often correlated,
      and do not have an additive effect, the impact of a metric on another i.e.
      interaction should be taken into account. The effect of interaction in developing
      regression based fault prediction models is uncommon in software engineering;
      however two terms and three term interactions are analyzed in detail in social
      and behavioral sciences. Beyond three terms interactions are scarce, because
      interaction effects at such a high level are difficult to interpret. From our
      earlier findings (Softw Qual Prof 15(3):15-23) we statistically establish the
      pertinence of considering the interaction between metrics resulting in a
      considerable improvement in the explanatory power of the corresponding predictive
      model. However, in the aforesaid approach, the number of variables involved in
      fault prediction also shows a simultaneous increment with interaction.
      Furthermore, the interacting variables do not contribute equally to the
      prediction capability of the model. This study contributes towards the
      development of an efficient predictive model involving interaction among
      predictive variables with a reduced set of influential terms, obtained by
      applying stepwise regression. 

PMID- 24324927
TI  - Flat-pressed wood plastic composites from sawdust and recycled polyethylene
      terephthalate (PET): physical and mechanical properties.
AB  - This study deals with the fabrication of composite matrix from saw dust (SD) and
      recycled polyethylene terephthalate (PET) at different ratio (w/w) by flat
      pressed method. The wood plastic composites (WPCs) were made with a thickness of
      6 mm after mixing the saw dust and PET in a rotary type blender followed by flat
      press process. Physical i.e., density, moisture content (MC), water absorption
      (WA) and thickness swelling (TS), and mechanical properties i.e., Modulus of
      Elasticity (MOE) and Modulus of Rupture (MOR) were assessed as a function of
      mixing ratios according to the ASTM D-1037 standard. WA and TS were measured
      after 24 hours of immersion in water at 25, 50 and 75 degrees C temperature. It
      was found that density decreased 18.3% when SD content increased from 40% to 70%
      into the matix. WA and TS increased when the PET content decreased in the matrix
      and the testing water temperature increased. MOE and MOR were reached to maximum
      for the fabricated composites (2008.34 and 27.08 N/mm(2), respectively) when the
      SD content were only 40%. The results indicated that the fabrication of WPCs from
      sawdust and PET would technically feasible; however, the use of additives like
      coupling agents could further enhance the properties of WPCs. 

PMID- 24324928
TI  - Growth rates of larval and juvenile bigeye scad Selar crumenophthalmus in
      captivity.
AB  - Growth rates of larval and juvenile bigeye scad Selar crumenophthalmus reared in
      captivity were studied. The results are presented, discussed, and compared to
      wild S. crumenophthalmus and other pelagic fish. S. crumenophthalmus are a small
      pelagic carangid fish of circumtropical distribution. Larvae were reared in a
      modified mesocosm system and sampled daily for growth. Larvae grew to a mean size
      of 4.74 cm (Standard Length) and 1.30 g by 45 days post hatch (dph). Larval
      length-at-age was best described by the exponential equation Y = 1.966e(0.0704t)
      . For juvenile growth trials, 1940 fish were stocked into four 2.5 m(3) cylindro
      conical tanks at two different densities (262 fish m(-3) and 120 fish m(-3)) and
      reared from 45 dph to subadult stage. Fish were sampled daily for growth. No
      statistically significant differences in growth or survival were detected between
      tanks. Mean length and weight at 141 dph was 13.24 cm (Total Length) and 25.20 g.
      Juvenile length-at-age was best described by the Von Bertalanffy Growth Model
      equation L t  = 27.75(1 - e(-0.03(t-1.57))). Weight-at-age was best described by
      a linear equation W t = 1.7313x + 12.4662. The exponent of the length-weight
      equation was 3.14. In addition to providing the first published description of
      larviculture and juvenile growout techniques for S. crumenophthalmus, this study
      contains the first published data on this species' larval growth and directly
      confirms estimates of S. crumenophthalmus juvenile growth done by other
      researchers using indirect techniques such as otolith daily growth increment and
      frequency distribution analysis. 

PMID- 24324929
TI  - Persistent fear of aftershocks, impairment of working memory, and acute stress
      disorder predict post-traumatic stress disorder: 6-month follow-up of help
      seekers following the L'Aquila earthquake.
AB  - The aim of our 6-month follow-up study was to assess predictors of post-traumatic
      stress disorder (PTSD) among individuals seeking treatment at the General
      Hospital Psychiatric Unit within the first month following the L'Aquila
      earthquake. Clinical, trauma-related and neurocognitive variables were
      considered. At the 6-month follow-up, 91 (74.5%) out of 122 subjects were re
      assessed and administered the Impact of Events Scale-revised (IES-R) for the
      detection of PTSD according to DSM-IV criteria. Within 4 weeks following the
      earthquake, patients were assessed with a checklist of traumatic-event-related
      variables, along with the Stanford Acute Stress Disorder Questionnaire (SASDQ)
      for the detection of ASD, with a short battery on working (Wechler Memory Scale
      R, Digit Forward and Backward) and verbal memory (subtest of Milan Overall
      Dementia Assessment, MODA). A statistically significant higher proportion of
      subjects affected by 'partial' ASD showed a PTSD diagnosis (80.6%, N = 29)
      compared to not diagnosed subjects (40%, N = 22) and a PTSD diagnosis was shown
      by all the 4 subjects (4.4%) affected by 'full' ASD at the entry in the study. At
      the 6-month follow-up 56% of the sample could be considered affected by PTSD on
      the IES-R scale. The results of the logistic regression analysis on our selected
      predictors indicated that the persistent fear of aftershocks seemed to increase
      by over 57 times the likelihood of positive estimate of PTSD, followed by
      impairment of working memory backward (OR 48.2), and having being diagnosed as
      ASD case in the first 4 week after the earthquake (OR 17.4). This study
      underlines the importance of identifying PTSD predictors, in order to planning
      early treatment interventions after natural disasters. 

PMID- 24324930
TI  - Endogenous mouse mammary tumor viruses (mtv): new roles for an old virus in
      cancer, infection, and immunity.
AB  - Mouse Mammary Tumor Viruses are beta-retroviruses that exist in both exogenous
      (MMTV) and endogenous (Mtv) forms. Exogenous MMTV is transmitted via the milk of
      lactating animals and is capable of inducing mammary gland tumors later in life.
      MMTV has provided a number of critical models for studying both viral infection
      as well as human breast cancer. In addition to the horizontally transmitted MMTV,
      most inbred mouse strains contain permanently integrated Mtv proviruses within
      their genome that are remnants of MMTV infection and vertically transmitted.
      Historically, Mtv have been appreciated for their role in shaping the T cell
      repertoire during thymic development via negative selection. In addition, more
      recent work has demonstrated a larger role for Mtv in modulating host immune
      responses due to its peripheral expression. The influence of Mtv on host response
      has been observed during experimental murine models of Polyomavirus- and ESb
      induced lymphoma as well as Leishmania major and Plasmodium berghei ANKA
      infection. Decreased susceptibility to bacterial pathogens and virus-induced
      tumors has been observed among mice lacking all Mtv. We have also demonstrated a
      role for Mtv Sag in the expansion of regulatory T cells following chronic viral
      infection. The aim of this review is to summarize the latest research in the
      field regarding peripheral expression of Mtv with a particular focus on their
      role and influence on the immune system, infectious disease outcome, and
      potential involvement in tumor formation. 

PMID- 24324931
TI  - A Predictive Genetic Signature for Response to Fluoropyrimidine-Based Neoadjuvant
      Chemoradiation in Clinical Stage II and III Rectal Cancer.
AB  - PURPOSE: Pre-operative chemoradiation (CRT) is currently the standard of care for
      patients with clinical stage II and III rectal cancer but only about 45% of
      patients achieve tumor downstaging and <20% of patients achieve a pathologic
      complete response. Better methods to stratify patients according to potential
      neoadjuvant treatment response are needed. We used microarray analysis to
      identify a genetic signature that correlates with a pathological complete
      response (pCR) to neoadjuvant CRT. We performed a gene network analysis to
      identify potential signaling pathways involved in determining response to
      neoadjuvant treatment. PATIENTS AND METHODS: We identified 31 T3-4 N0-1 rectal
      cancer patients who were treated with neoadjuvant fluorouracil-based CRT. Eight
      patients were identified to have achieved a pCR to treatment while 23 patients
      did not. mRNA expression was analyzed using cDNA microarrays. The correlation
      between mRNA expression and pCR from pre-treatment tumor biopsies was determined.
      Gene network analysis was performed for the genes represented by the predictive
      signature. RESULTS: A genetic signature represented by expression levels of the
      three genes EHBP1, STAT1, and GAPDH was found to correlate with a pCR to
      neoadjuvant treatment. The difference in expression levels between patients who
      achieved a pCR and those who did not was greatest for EHBP1. Gene network
      analysis showed that the three genes can be connected by the gene ubiquitin C
      (UBC). CONCLUSION: This study identifies a 3-gene signature expressed in pre
      treatment tumor biopsies that correlates with a pCR to neoadjuvant CRT in
      patients with clinical stage II and III rectal cancer. These three genes can be
      connected by the gene UBC, suggesting that ubiquitination is a molecular
      mechanism involved in determining response to treatment. Validating this genetic
      signature in a larger number of patients is proposed.

PMID- 24324932
TI  - Feasibility of tomotherapy-based image-guided radiotherapy for small cell lung
      cancer.
AB  - BACKGROUND: To assess the tolerance of patients with small cell lung cancer
      undergoing chemoradiation with tomotherapy-based image-guided radiotherapy
      (IGRT). MATERIALS AND METHODS: A retrospective review of the toxicity profile for
      nine patients with small cell lung cancer of the limited stage who underwent
      chemoradiation delivered with helical tomotherapy (HT) has been conducted.
      RESULTS: Acute grade 3-4 hematologic and esophagitis toxicities developed in two
      and three patients respectively. One patient developed a pulmonary embolism
      during radiotherapy. Seven patients had weight loss ranging from 0 to 30 pounds
      (median: 4 pounds). Three patients had treatment breaks ranging from 2 to 12
      days. At a median follow-up of 11 months (range: 2-24 months), no patients
      developed any radiation related toxicities such as grade 3-4 pneumonitis or other
      long-term complications. The median survival was estimated to be 15 months. There
      were two local recurrences, three mediastinal recurrences, and six distant
      metastases. CONCLUSION: Grade 3-4 toxicities remained significant during
      chemoradiation when radiation was delivered with tomotherapy-based IGRT. However,
      the absence of grade 3-4 pneumonitis is promising and the use of HT needs to be
      investigated in future prospective studies.

PMID- 24324934
TI  - Welcome to a new stroke journal.

PMID- 24324935
TI  - Stroke statistics in Korea: part I. Epidemiology and risk factors: a report from
      the korean stroke society and clinical research center for stroke.
AB  - The aim of the Part I of Stroke Statistics in Korea is to summarize nationally
      representative data of the epidemiology and risk factors of stroke in a single
      document. Every year, approximately 105,000 people experience a new or recurrent
      stroke and more than 26,000 die of stroke, which indicates that every 5 minutes
      stroke attacks someone and every 20 minutes stroke kills someone in Korea. Stroke
      accounts for roughly 1 of every 10 deaths. The estimated stroke prevalence is
      about 795,000 in people aged >=30 years. The nationwide total cost for stroke
      care was 3,737 billion Korean won (US$3.3 billion) in 2005. Fortunately, the
      annual stroke mortality rate decreased substantially by 28.3% during the first
      decade of the 21th century (53.2/100,000 in 2010). Among OECD countries, Korea
      had the lowest in-hospital 30-day case-fatality rate for ischemic stroke and
      ranked third lowest for hemorrhagic stroke in 2009. The proportion of ischemic
      stroke has steadily increased and accounted for 76% of all strokes in 2009.
      According to hospital registry studies, the 90-day mortality rate was 3-7% for
      ischemic stroke and 17% for intracerebral hemorrhage. For risk factors, among
      Korean adults >=30 years of age, one in 3-4 has hypertension, one in 10 diabetes,
      and one in 7 hypercholesterolemia. One in 3 Korean adults >=19 years of age is
      obese. Over the last 10 years, the prevalence of hypertension slightly decreased,
      but the prevalence of diabetes, hypercholesterolemia, and obesity increased.
      Smoking prevalence in men has decreased, but is still as high as 48%. This report
      could be a valuable resource for establishing health care policy and guiding
      future research directions. 

PMID- 24324933
TI  - Subversion of inflammasome activation and pyroptosis by pathogenic bacteria.
AB  - Activation of the inflammasome occurs in response to a notably high number of
      pathogenic microbes and is a broad innate immune response that effectively
      contributes to restriction of pathogen replication and generation of adaptive
      immunity. Activation of these platforms leads to caspase-1- and/or caspase-11
      dependent secretion of proteins, including cytokines, and induction of a specific
      form of cell death called pyroptosis, which directly or indirectly contribute for
      restriction of pathogen replication. Not surprisingly, bona fide intracellular
      pathogens developed strategies for manipulation of cell death to guarantee
      intracellular replication. In this sense, the remarkable advances in the
      knowledge of the inflammasome field have been accompanied by several reports
      characterizing the inhibition of this platform by several pathogenic bacteria.
      Herein, we review some processes used by pathogenic bacteria, including Yersinia
      spp., Pseudomonas aeruginosa, Vibrio parahaemolyticus, Chlamydia trachomatis,
      Francisella tularensis, Shigella flexneri, Legionella pneumophila, and Coxiella
      burnetii to evade the activation of the inflammasome and the induction of
      pyroptosis. 

PMID- 24324936
TI  - Epidemiology and registry studies of stroke in Japan.
AB  - Stroke is the most prevalent cardiovascular disease in Japan. This review
      introduces two epidemiologic studies and four registry studies of stroke in
      Japan. The Hisayama Study was begun as a population-based prospective cohort
      study of cerebrovascular and cardiovascular diseases in 1961 in the town of
      Hisayama. Most of the deceased subjects of the study underwent autopsy
      examinations from the beginning of the study. Changes in stroke trends in the
      last 50 years were clarified by comparison of data from different study cohorts
      registered every 13 to 14 years. The Suita Study was based on a random sampling
      of Japanese urban residents. Several reports from this study showed the
      significance of pre-hypertension, as well as hypertension, as a risk factor for
      stroke by itself and in combination with other underlying characteristics. In
      addition, the Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC),
      the Japan Standard Stroke Registry Study, the Fukuoka Stroke Registry, and the
      Stroke Acute Management with Urgent Risk-factor Assessment and Improvement
      (SAMURAI) rt-PA Registry are explained as registry studies involving Japanese
      stroke patients. 

PMID- 24324937
TI  - Biomarkers for stroke.
AB  - BACKGROUND: Major stroke clinical trials have failed during the past decades. The
      failures suggest the presence of heterogeneity among stroke patients. Biomarkers
      refer to indicators found in the blood, other body fluids or tissues that
      predicts physiologic or disease states, increased disease risk, or pharmacologic
      responses to a therapeutic intervention. Stroke biomarkers could be used as a
      guiding tool for more effective personalized therapy. MAIN CONTENTS: Three
      aspects of stroke biomarkers are explored in detail. First, the possible role of
      biomarkers in patients with stroke is discussed. Second, the limitations of
      conventional biomarkers (especially protein biomarkers) in the area of stroke
      research are presented with the reasons. Lastly, various types of biomarkers
      including traditional and novel genetic, microvesicle, and metabolomics
      associated biomarkers are introduced with their advantages and disadvantages. We
      especially focus on the importance of comprehensive approaches using a variety of
      stroke biomarkers. CONCLUSION: Although biomarkers are not recommended in
      practice guidelines for use in the diagnosis or treatment of stroke, many efforts
      have been made to overcome the limitations of biomarkers. The studies reviewed
      herein suggest that comprehensive analysis of different types of stroke
      biomarkers will improve the understanding of individual pathophysiologies and
      further promote the development of screening tools for of high-risk patients, and
      predicting models of stroke outcome and rational stroke therapy tailored to the
      characteristics of each case.

PMID- 24324938
TI  - Carotid intima-media thickness studies: study design and data analysis.
AB  - BACKGROUND: Carotid intima-media thickness (CIMT) measurements have been widely
      used as primary endpoint in studies into the effects of new interventions as
      alternative for cardiovascular morbidity and mortality. There are no accepted
      standards on the use of CIMT measurements in intervention studies and choices in
      the design and analysis of a CIMT study are generally based on experience and
      expert opinion. In the present review, we provide an overview of the current
      evidence on several aspects in the design and analysis of a CIMT study on the
      early effects of new interventions. SUMMARY OF ISSUES: A balanced evaluation of
      the carotid segments, carotid walls, and image view to be used as CIMT study
      endpoint; the reading method (manual or semi-automated and continuously or in
      batch) to be employed, the required sample size, and the frequency of ultrasound
      examinations is provided. We also discuss the preferred methods to analyse
      longitudinal CIMT data and address the possible impact of, and methods to deal
      with missing and biologically implausible CIMT values. CONCLUSIONS: Linear mixed
      effects models are the preferred way to analyse CIMT data and do appropriately
      handle missing and biologically implausible CIMT values. Furthermore, we
      recommend to use extensive CIMT designs that measure CIMT at regular points
      during the multiple carotid sites as such approach is likely to increase the
      success rates of CIMT intervention studies designed to evaluate the effects of
      new interventions on atherosclerotic burden.

PMID- 24324939
TI  - Impact of post-stroke cognitive impairment with no dementia on health-related
      quality of life.
AB  - BACKGROUND AND PURPOSE: Health-related quality of life (HRQoL) is a
      multidimensional concept that signifies a subjective evaluation of perceived
      health; hence, it has gained wide acceptance in geriatrics. However, its
      application has not been tested in patients with post-stroke cognitive impairment
      with no dementia (PSCIND). We investigated whether PSCIND interferes with HRQoL
      measured by EQ-5D, compared the findings to those of healthy people with normal
      cognition, and evaluated the influence of each cognitive domain on this score.
      METHODS: In total, 1,528 subjects were identified who had undergone
      neuropsychological assessment using the 60-min protocol of the Korean version of
      Vascular Cognitive Impairment Harmonization Standards, EQ-5D, and magnetic
      resonance imaging at the stroke prevention clinic. Fifty PSCIND patients were
      matched to 50 post-stroke dementia (PSD) patients and 50 normal age- (+/-3 years)
      and sex-matched controls. The effects of PSCIND, PSD, and control groups upon the
      EQ-5Dindex score were tested by generalized estimating equation modeling.
      RESULTS: Estimated means+/-standard errors of EQ-5Dindex scores were as follows:
      0.94+/-0.06 (control group), 0.86+/-0.08 (PSCIND group), and 0.61+/-0.32 (PSD
      group); and the difference among the three groups was statistically significant
      (P<0.0001). Pairwise comparisons showed that EQ-5Dindex scores in the PSCIND
      group differed from those in the PSD and control groups (both P<0.01). No
      cognitive domain was specifically associated with EQ-5Dindex scores after
      adjusting for functional status. CONCLUSIONS: This study shows that PSCIND may
      interfere with the quality of life in stroke victims.

PMID- 24324940
TI  - Organized Comprehensive Stroke Center is Associated with Reduced Mortality:
      Analysis of Consecutive Patients in a Single Hospital.
AB  - BACKGROUND AND PURPOSE: Organized inpatient stroke care is one of the most
      effective therapies for improving patient outcomes. Many stroke centers have been
      established to meet this need, however, there are limited data on the
      effectiveness of these organized comprehensive stroke center (CSC) in the real
      world setting. Our aim is to determine whether inpatient care following the
      establishment of CSC lowers mortality of patients with acute ischemic stroke
      (AIS). METHODS: Based on a prospective stroke registry, we identified AIS
      patients hospitalized before and after the establishment of a CSC. We observed
      all-cause mortality within 30 days from time of admission. Logistic regression
      was used to determine whether the establishment of the CSC affects independently
      the 30-day all-cause mortality. RESULTS: A total of 3,117 consecutive patients
      with AIS were admitted within seven days after the onset of the symptoms.
      Unadjusted 30-day mortality was lower for patients admitted to our hospital after
      the establishment of the CSC than before (5.9% vs. 8.2%, P=0.012). Advanced age,
      female gender, previous coronary artery disease, non-smoking, stroke subtype,
      admission on a holiday, referral from other hospitals, high NIHSS on admission,
      and admission before the establishment of CSC were associated with increased 30
      day stroke case fatality. After adjustment for these factors, stroke inpatient
      care subsequent to the establishment of the CSC was independently associated with
      lower 30-day mortality (OR, 0.57; 95% CI, 0.412-0.795). CONCLUSIONS: Patients
      treated after the establishment of a CSC had lower 30-mortality rates than ever
      before, even adjusting for the differences in the baseline characteristics. The
      present study reveals that organized stroke care in a CSC might improve the
      outcome after AIS.

PMID- 24324941
TI  - Facial palsy and nystagmus after transvenous embolization of a carotid cavernous
      fistula.

PMID- 24324942
TI  - Stroke Statistics in Korea: Part II Stroke Awareness and Acute Stroke Care, A
      Report from the Korean Stroke Society and Clinical Research Center For Stroke.
AB  - The aim of the current Part II of Stroke Statistics in Korea is to summarize
      nationally representative data on public awareness, pre-hospital delay,
      thrombolysis, and quality of acute stroke care in a single document. The public's
      knowledge of stroke definition, risk factors, warning signs, and act on stroke
      generally remains low. According to studies using open-ended questions, the
      correct definition of stroke was recognized in less than 50%, hypertension as a
      stroke risk factor in less than 50%, and other well-defined risk factors in less
      than 20%. Among stroke warning signs, sudden paresis or numbness was best
      appreciated, with recognition rates ranging in 36.9-73.7%, but other warning
      signs including speech disturbance were underappreciated. In addition, less than
      one third of subjects in a representative population survey were aware of
      thrombolysis and had knowledge of the appropriate act on stroke, calling
      emergency medical services (EMS). Despite EMS being an essential element in the
      stroke chain of survival and outcome improvement, EMS protocols for field stroke
      diagnosis and prehospital notification for potential stroke patients are not well
      established. According to the Assessment for Quality of Acute Stroke Care, the
      median onset-to-door time for patients arriving at the emergency room was 4 hours
      (mean, 17.3 hours) in 2010, which was not reduced compared to 2005. In contrast,
      the median door-to-needle time for intravenous tissue plasminogen activator (IV
      TPA) treatment was 55.5 minutes (mean, 79.5 minutes) in 2010, shorter than the
      median time of 60.0 minutes (mean, 102.8 minutes) in 2008. Of patients with acute
      ischemic stroke, 7.9% were treated with IV-TPA in 2010, an increase from the 4.6%
      in 2005. Particularly, IV-TPA use for eligible patients substantially increased,
      from 21.7% in 2005 to 74.0% in 2010. The proportion of hospitals equipped with a
      stroke unit has increased from 1.1% in 2005 to 19.4% in 2010. Performance, as
      measured by quality indicators, has steadily improved since 2005, and the
      performance rates for most indicators were greater than 90% in 2010 except for
      early rehabilitation consideration (89.4%) and IV-TPA use for eligible patients
      (74.0%). In summary, the current report indicates a substantial improvement in in
      hospital acute stroke care, but also emphasizes the need for enhancing public
      awareness and integrating the prehospital EMS system into acute stroke
      management. This report would be a valuable resource for understanding the
      current status and implementing initiatives to further improve public awareness
      of stroke and acute stroke care in Korea. 

PMID- 24324943
TI  - Primary and comprehensive stroke centers: history, value and certification
      criteria.
AB  - In the United States (US) stroke care has undergone a remarkable transformation
      in the past decades at several levels. At the clinical level, randomized trials
      have paved the way for many new stroke preventives, and recently, several new
      mechanical clot retrieval devices for acute stroke treatment have been cleared
      for use in practice by the US Federal Drug Administration. Furthermore, in the
      mid 1990s we witnessed regulatory approval of intravenous recombinant tissue
      plasminogen activator for administration in acute ischemic stroke. In the domain
      of organization of medical care and delivery of health services, stroke has
      transitioned from a disease dominated by neurologic consultation services only to
      one managed by vascular neurologists in geographical stroke units, stroke teams
      and care pathways, primary stroke center certification according to The Joint
      Commission, and most recently comprehensive stroke center designation under the
      aegis of The Joint Commission. Many organizations in the US have been involved to
      enhance stroke care. To name a few, the American Heart Association/American
      Stroke Association, Brain Attack Coalition, and National Stroke Association have
      been on the forefront of this movement. Additionally, governmental initiatives by
      the US Centers for Disease Control and Prevention and legislative initiatives
      such as the Paul Coverdell National Acute Stroke Registry program have paved the
      way to focus on stroke prevention, acute treatment and quality improvement. In
      this invited review, we discuss a brief history of organized stroke care in the
      United States, evidence to support the value of primary and comprehensive stroke
      centers, and the certification criteria and process to become a primary or
      comprehensive stroke center. 

PMID- 24324944
TI  - Review of stroke thrombolytics.
AB  - The cornerstone of acute ischemic stroke treatment relies on rapid clearance of
      an offending thrombus in the cerebrovascular system. There are various drugs and
      different methods of assessment to select patients more likely to respond to
      treatment. Current clinical guidelines recommend the administration of
      intravenous alteplase (following a brain noncontract CT to exclude hemorrhage)
      within 4.5 hours of stroke onset. Because of the short therapeutic time window,
      the risk of hemorrhage, and relatively limited efficacy of alteplase for large
      clot burden, research is ongoing to find more effective and safer reperfusion
      therapy, as well as focussing on refinement of patient selection for acute
      reperfusion treatment. Studies using advanced imaging (incorporating perfusion CT
      or diffusion/perfusion MRI) may allow us to use thrombolytics, or possibly
      endovascular therapy, in an extended time window. Recent clinical trials have
      suggested that Tenecteplase, used in conjunction with advanced imaging selection,
      resulted in more effective reperfusion than alteplase, which translated into
      increased clinical benefit. Studies using Desmoteplase have suggested its
      potential benefit in a sub-group of patients with large artery occlusion and
      salveageable tissue, in an extended time window. Other ways to improve acute
      reperfusion approaches are being actively explored, including endovascular
      therapy, and the enhancement of thrombolysis by ultrasound insonation of the clot
      (sono-thrombolysis). 

PMID- 24324945
TI  - Multimodality monitoring in the neurointensive care unit: a special perspective
      for patients with stroke.
AB  - Multimodality monitoring (MMM) is a recently developed method that aids in
      understanding real-time brain physiology. Early detection of physiological
      disturbances is possible with the help of MMM, which allows identification of
      underlying causes of deterioration and minimization of secondary brain injury
      (SBI). MMM is especially helpful in comatose patients with severe brain injury
      because neurological examinations are not sensitive enough to detect SBI. The
      variables frequently examined in MMM are hemodynamic parameters such as
      intracranial pressure, cerebral perfusion pressure, and mean arterial pressure;
      brainspecific oxygen tension; markers for brain metabolism including glucose,
      lactate, and pyruvate levels in brain tissue; and cerebral blood flow. Continuous
      electroencephalography can be performed, if needed. The majority of SBIs stem
      from brain tissue hypoxia, brain ischemia, and seizures, which lead to a
      disturbance in brain oxygen levels, cerebral blood flow, and electrical
      discharges, all of which are easily detected by MMM. In this review, we discuss
      the clinical importance of physiological variables as well as the practical
      applicability of MMM in patients with stroke. 

PMID- 24324946
TI  - Epidemiological factors of stroke: a survey of the current status in china.
AB  - Stroke is the leading cause of death in China and confers a huge burden and
      effort on patients and health professionals. China has the world's largest
      population and has been experiencing a rapid economic development. In this
      article, we review the current status of stroke epidemiological features and risk
      factors, and the recently ongoing stroke epidemiological survey in China.
      Epidemiological studies suggested that stroke incidence increases with age and
      that the elderly population is expected to increase over time in China. Stroke
      mortality increased gradually from 1990 to 2000 but declined since the beginning
      of the 21st century, probably related to better control of vascular risk factors
      and the advances in acute stroke care. The Chinese lifestyle has changed rapidly
      during the past 3 decades. Moreover, China is a big country with substantial
      geographic disparities. The geographical variation and chronological trend of
      vascular risk factors may determine changes in the prevalence and subtypes of
      stroke in China. In this review, the current Chinese researches on the critical
      management of stroke and the potential direction and support of the Chinese
      government are discussed. 

PMID- 24324947
TI  - VKORC1 and CYP2C9 Genotype Variations in Relation to Warfarin Dosing in Korean
      Stroke Patients.
AB  - BACKGROUND AND PURPOSE: Variant alleles of CYP2C9 and VKORC1 account for
      differences in anticoagulation response. We sought to establish a warfarin dosing
      formula for individualized target International Normalization Ratio of
      Prothrombin Times (INRs) using data from single nucleotide polymorphisms (SNPs)
      in VKORC1 and CYP2C9 in Korean patients. METHODS: Ischemic stroke patients
      displaying stable target INR for at least 3 months before enrollment were
      analyzed. Warfarin and vitamin K levels were measured to adjust for confounders.
      Phenotypes were defined using the 'warfarin response index' (WRI) defined as INR
      divided by the daily maintenance warfarin dose. We tested SNPs in CYP2C9 (3
      sites: 430C>T (rs1799853), 1075A>C (rs1057910), 1076T>C) and VKORC1 (14 sites:
      381C>T, 861C>A (rs17880887), 2653G>C, 3673A>G, 5496G>T, 5808T>G (r17882154),
      6009C>T, 6484T>C (rs9934438), 6853C>T (rs17886369), 7566T>C, 8767G>C, 8814T>C,
      9041G>A (rs17880624), and 9071G>T) using a standard sequencing method.
      Multivariate linear regression analysis was applied to establish the formula for
      warfarin dosage. RESULTS: All 204 patients had excellent drug compliance. The
      mean INR was 2.22 (+0.56) and mean daily maintenance dose of warfarin was 3.92 mg
      (+1.54). Patients with low WRI were younger (P<0.001) with high body mass index
      (P=0.003), high prevalence of wild-type CYP2C9 polymorphism (1075A>C, P<0.001),
      and six heterozygote SNPs in VRORC1 (P<0.001), which were tightly interlinked
      (381T>C, 3673G>A, 6484T>C, 6853C>G. 7566C>T, 9041G>A) (r(2)=1). Based on these
      data, a warfarin dosing formula was established. CONCLUSIONS: WRI is influenced
      by age, body mass index and SNPs in VKORC1 and CYP2C9 in Korean stroke patients.
      The obtained warfarin dosing formula may be clinically applicable.

PMID- 24324948
TI  - Association of aortic knob calcification with intracranial stenosis in ischemic
      stroke patients.
AB  - BACKGROUND AND PURPOSE: Aortic knob calcification (AC) is associated with
      increased risks of cardiovascular and cerebrovascular events. We evaluated the
      clinical importance of AC in ischemic stroke patients with intracranial (IC)
      stenosis using simple, non-invasive and routine chest radiography. METHODS: The
      presence of AC was assessed in a chest posteroanterior view in 307 acute ischemic
      stroke patients admitted from May 2009 to April 2010, and who underwent magnetic
      resonance angiography or distal subtraction angiography. The association of AC
      with IC stenosis was analyzed. RESULTS: Patient age (68.3+/-8.7 vs. 65.9+/-8.27
      years, P=0.04), and the prevalence of IC stenosis (70.7 vs. 41.3%, P<0.01) were
      higher in patients with AC than in patients without calcification. After
      adjusting for age, gender and vascular risk factors, logistic regression analysis
      showed that AC (Odds ratio, 3.54; 95% confidence interval, 1.90 to 6.61, P<0.01)
      and age (Odds ratio, 1.79; 95% confidence interval, 1.01 to 3.19; P=0.04) were
      independent factors affecting IC stenosis. CONCLUSIONS: AC appears to be a
      reliable predictor for IC stenosis, an important mechanism of ischemic stroke.

PMID- 24324949
TI  - Prostate carcinoma in transgenic Lewis rats - a tumor model for evaluation of
      immunological treatments.
AB  - Transgenic rodent models of prostate cancer have served as valuable preclinical
      models to evaluate novel treatments and understand malignant disease progression.
      In particular, a transgenic rat autochthonous model of prostate cancer using the
      SV40 large T antigen expressed under a prostate-specific probasin promoter was
      previously developed as a model of androgen-dependent prostate cancer (TRAP). In
      the current report, we backcrossed this strain to the Lewis strain, an inbred rat
      strain better characterized for immunological analyses. We demonstrate that Lewis
      transgenic rats (Lew-TRAP) developed prostate adenocarcinomas with 100%
      penetrance by 25 weeks of age. Tumors were predominantly androgen-dependent, as
      castration prevented tumor growth in the majority of animals. Finally, we
      demonstrate that Lew-TRAP rats could be immunized with a DNA vaccine encoding a
      human prostate tumor antigen (prostatic acid phosphatase) with the development of
      Lewis strain-specific T-cell responses. We propose that this Lew-TRAP strain, and
      prostate tumor cell lines derived from this strain, can be used as a future
      prostate cancer immunotherapy model.

PMID- 24324950
TI  - Extracting evolutionary insights using bioinformatics.

PMID- 24324951
TI  - Prevalence of bronchiectasis in asthma according to oral steroid requirement:
      influence of immunoglobulin levels.
AB  - PURPOSE: To establish the prevalence of bronchiectasis in asthma in relation to
      patients' oral corticosteroid requirements and to explore whether the increased
      risk is due to blood immunoglobulin (Ig) concentration. METHODS: Case-control
      cross-sectional study, including 100 sex- and age-matched patients, 50 with non
      steroid-dependent asthma (NSDA) and 50 with steroid-dependent asthma (SDA). STUDY
      PROTOCOL: (a) measurement of Ig and gG subclass concentration; (b) forced
      spirometry; and (c) high-resolution thoracic computed tomography. When
      bronchiectasis was detected, a specific etiological protocol was applied to
      establish its etiology. RESULTS: The overall prevalence of bronchiectasis was
      12/50 in the SDA group and 6/50 in the NSDA group (p = ns). The etiology was
      documented in six patients (four NSDA and two SDA). After excluding these
      patients, the prevalence of bronchiectasis was 20% (10/50) in the SDA group and
      2/50 (4%) in the NSDA group (P < 0.05). Patients with asthma-associated
      bronchiectasis presented lower FEV1 values than patients without bronchiectasis,
      but the levels of Ig and subclasses of IgG did not present differences.
      CONCLUSIONS: Steroid-dependent asthma seems to be associated with a greater risk
      of developing bronchiectasis than non-steroid-dependent asthma. This is probably
      due to the disease itself rather than to other influencing factors such as
      immunoglobulin levels.

PMID- 24324952
TI  - Development of a novel reference plasmid for accurate quantification of
      genetically modified Kefeng6 rice DNA in food and feed samples.
AB  - Reference plasmids are an essential tool for the quantification of genetically
      modified (GM) events. Quantitative real-time PCR (qPCR) is the most commonly used
      method to characterize and quantify reference plasmids. However, the precision of
      this method is often limited by calibration curves, and qPCR data can be affected
      by matrix differences between the standards and samples. Here, we describe a
      digital PCR (dPCR) approach that can be used to accurately measure the novel
      reference plasmid pKefeng6 and quantify the unauthorized variety of GM rice
      Kefeng6, eliminating the issues associated with matrix effects in calibration
      curves. The pKefeng6 plasmid was used as a calibrant for the quantification of
      Kefeng6 rice by determining the copy numbers of event- (77 bp) and taxon-specific
      (68 bp) fragments, their ratios, and their concentrations. The plasmid was
      diluted to five different concentrations. The third sample (S3) was optimized for
      the quantification range of dPCR according to previous reports. The ratio between
      the two fragments was 1.005, which closely approximated the value certified by
      sequencing, and the concentration was found to be 792 copies/MUL. This method was
      precise, with an RSD of ~3%. These findings demonstrate the advantages of using
      the dPCR method to characterize reference materials.

PMID- 24324953
TI  - Traumatic brain injury related hospitalization and mortality in California.
AB  - OBJECTIVE: The aim of this study is to describe the traumatic brain injury (TBI)
      population and causes and identify factors associated with TBI hospitalizations
      and mortality in California. METHODS: This is a cross-sectional study of 61,188
      patients with TBI from the California Hospital Discharge Data 2001 to 2009. We
      used descriptive, bivariate, and multivariate analyses in SAS version 9.3.
      RESULTS: TBI-related hospitalizations decreased by 14% and mortality increased by
      19% from 2001 to 2009. The highest percentages of TBI hospitalizations were due
      to other causes (38.4%), falls (31.2%), being of age >=75 years old (37.2%),
      being a males (58.9%), and being of Medicare patients (44%). TBIs due to falls
      were found in those age <=4 years old (53.5%), >=75 years old (44.0%), and
      females (37.2%). TBIs due to assaults were more frequent in Blacks (29.0%). TBIs
      due to motor vehicle accidents were more frequent in 15-19 and 20-24 age groups
      (48.7% and 48.6%, resp.) and among Hispanics (27.8%). Higher odds of mortality
      were found among motor vehicle accident category (adjusted odds ratio (AOR):
      1.27, 95% CI: 1.14-1.41); males (AOR: 1.36, 95% CI: 1.27-1.46); and the >=75-year
      old group (AOR: 6.4, 95% CI: 4.9-8.4). CONCLUSIONS: Our findings suggest a
      decrease in TBI-related hospitalizations but an increase in TBI-related mortality
      during the study period. The majority of TBI-related hospitalizations was due to
      other causes and falls and was more frequent in the older, male, and Medicare
      populations. The higher likelihood of TBI-related mortalities was found among
      elderly male >=75 years old who had motor vehicle accidents. Our data can inform
      practitioners, prevention planners, educators, service sectors, and policy makers
      who aim to reduce the burden of TBI in the community. Implications for
      interventions are discussed.

PMID- 24324954
TI  - Vignetting and field of view with the KAMRA corneal inlay.
AB  - PURPOSE: To evaluate the effect of the KAMRA corneal inlay on the retinal image
      brightness in the peripheral visual field. METHODS: A KAMRA inlay was "implanted"
      into a theoretical eye model in a corneal depth of 200 microns. Corneal radius
      was varied to a steep, normal, and flat (7.37, 7.77, and 8.17 mm) version keeping
      the proportion of anterior to posterior radius constant. Pupil size was varied
      from 2.0 to 5.0 mm. Image brightness was determined for field angles from -70
      degrees  to 70 degrees  with and without KAMRA and proportion of light
      attenuation was recorded. RESULTS: In our parameter space, the attenuation in
      brightness ranges in between 0 and 60%. The attenuation in brightness is not
      affected by corneal shape. For large field angles where the incident ray bundle
      is passing through the peripheral cornea, brightness is not affected. For
      combinations of small pupil sizes (2.0 and 2.5 mm) and field angles of 20-40
      degrees , up to 60% of light may be blocked with the KAMRA. CONCLUSION: For
      combinations of pupil sizes and field angles, the attenuation of image brightness
      reaches levels up to 60%. Our theoretical findings have to be clinically
      validated with detailed investigation of this vignetting effect.

PMID- 24324955
TI  - Peanut sensitization profiles in Italian children and adolescents with specific
      IgE to peanuts.
AB  - Peanuts are one of the most relevant foods implicated in IgE-mediated adverse
      reactions in pediatric population. This study aimed to evaluate the pattern of
      sensitization towards five peanut allergenic components (rAra h 1, 2, 3, 8 and 9)
      in a population of Italian children and adolescents with specific IgE (sIgE) to
      peanut. rAra h 9 was the main allergen implicated in peanut sensitization (58%),
      followed by rAra h 8 (35%), rAra h 2 (27%), rAra h 3 (23%) and rAra h 1 (12.5%).
      rAra h 1, 2, and 3 were the main allergenic components in young children: 8/13
      (62%) between 2 and 5 years, 8/23 (35%) between 6 and 11 years, and 3/12 (25%)
      between 1 and 16 years. No differences were found among the levels of sIgE
      towards rAra h 1, 2, 3, and 9 in the three groups; in contrast, the levels of
      sIgE against rAra h 8 showed an increasing trend according to age. In conclusion
      rAra h 1, 2, and 3 were the prevalent sensitizing allergens during the first
      years of life in Italian patients with sIgE to peanuts ("genuine" allergy); in
      contrast rAra h 9 and 8 were mainly involved in school-age children and
      adolescents with pollen allergy ("secondary" sensitization). 

PMID- 24324956
TI  - Allicin attenuates inflammation and suppresses HLA-B27 protein expression in
      ankylosing spondylitis mice.
AB  - Here we aimed to determine the therapeutic effect of allicin on ankylosing
      spondylitis (AS) and explore the mechanism(s) of action. AS mouse model was
      constructed by transferring the HLA-B2704 gene into Kunming mice and verified by
      RT-PCR and CT imaging. Verified AS mice were randomly divided into model group (n
      = 6) and allicin-treated groups (50, 100, and 200 mg/kg, resp., n = 6, p.o., for
      2 months). Wild type mice were used as control (n = 6). The levels of AS-related
      inflammatory factors were measured by ELISA. mRNA and protein expressions of HLA
      B27 were checked by RT-PCR and western blotting. As the results, the mouse model
      of AS was successfully established, and high-dose allicin could markedly
      alleviate spine inflammatory injury possibly via reducing the secretion of the
      inflammatory factors (IL-6, IL-8, and TNF- alpha ) sharply in AS mice. Moreover,
      allicin significantly inhibited HLA-B27 protein translation but failed to
      suppress HLA-B27 gene transcription in AS mice, indicating a posttranscriptional
      mechanism of this modulation. In conclusion, allicin has potential to be used for
      AS treatment as an anti-inflammatory nutraceutical.

PMID- 24324957
TI  - Clinical epidemiology of reduced kidney function among elderly male fishing and
      agricultural population in Taipei, Taiwan.
AB  - PURPOSE: To quantify the prevalence of and associated factors for chronic kidney
      disease (CKD) among male elderly fishing and agricultural population in Taipei,
      Taiwan. METHODS: Subjects (n = 2,766) aged 65 years and over voluntarily admitted
      to a teaching hospital for a physical checkup were collected in 2010. CKD was
      defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS:
      Among these subjects, the over prevalence of chronic kidney disease was 13.6%
      (95% CI: 12.3-14.9%). The age-specific prevalence of CKD in 65-74 years, 75-84
      years, and >=85 years was 8.2%, 19.1%, and 27.0%, respectively. From the multiple
      logistic regression, age (OR = 1.05, 95% CI: 1.02-1.09), hyperuricemia (OR =
      2.94, 95% CI: 1.90-3.78), central obesity (OR = 1.17, 95% CI: 1.02-1.56),
      hyperglycemia (OR = 1.23, 95% CI: 1.11-1.67), hypertriglyceridemia (OR = 1.25,
      95% CI: 1.08-1.66), and lower HDL-C (OR = 1.61, 95% CI: 1.23-1.92) were
      statistically significantly related to CKD. The presence of metabolic components
      (one or two versus none, OR = 1.10, 95% CI: 1.04-1.25; three or more versus none,
      OR = 2.12, 95% CI: 1.86-2.78) also appeared to be statistically significantly
      related to CKD after adjustment for other independent factors. CONCLUSION:
      Several clinical factors independently affect the development of CKD in the
      elderly male fishing and agricultural population.

PMID- 24324958
TI  - The synergistic effects of low dose fluorouracil and TRAIL on TRAIL-resistant
      human gastric adenocarcinoma AGS cells.
AB  - The TNF-related apoptosis-inducing ligand (TRAIL) is a TNF family member which
      has been under intense focus because of its remarkable ability to induce
      apoptosis in malignant human cells while leaving normal cells unscathed. However,
      many cancer cells remain resistant to TRAIL. In this study, we had investigated
      the synergistic effects of low dose fluorouracil (5-Fu) and TRAIL on TRAIL
      resistant human gastric adenocarcinoma AGS cells and explored the potential
      mechanisms. Cell viability was analyzed by sulforhodamine B (SRB) assay and the
      synergistic effects were evaluated by Jin's formula and confirmed by both
      morphological changes under inverted microscope and flow cytometry. The
      expression of TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (DR5), TRAIL-R3 (decoy
      receptor, DcR1), TRAIL-R4 (DcR2), procaspase-3, procaspase-8, and procaspase-9
      was detected by western blotting. Our results showed that there were significant
      synergistic effects of low dose 5-Fu and TRAIL on TRAIL-resistant AGS cells, and
      this effect was supposed to be mediated by decreasing DcR2 expression and
      increasing DR5 expression. The extrinsic and intrinsic apoptosis pathways were
      both activated. The data suggest that combined treatment of low dose 5-Fu and
      TRAIL can be an effective therapeutic approach for gastric adenocarcinoma. 

PMID- 24324959
TI  - Assessing the detection capacity of microarrays as bio/nanosensing platforms.
AB  - Microarray is one of the most powerful detection systems with multiplexing and
      high throughput capability. It has significant potential as a versatile
      biosensing platform for environmental monitoring, pathogen detection, medical
      therapeutics, and drug screening to name a few. To date, however, microarray
      applications are still limited to preliminary screening of genome-scale
      transcription profiling or gene ontology analysis. Expanding the utility of
      microarrays as a detection tool for various biological and biomedical
      applications requires information about performance such as the limits of
      detection and quantification, which are considered as an essential information to
      decide the detection sensitivity of sensing devices. Here we present a
      calibration design that integrates detection limit theory and linear dynamic
      range to obtain a performance index of microarray detection platform using
      oligonucleotide arrays as a model system. Two different types of limits of
      detection and quantification are proposed by the prediction or tolerance interval
      for two common cyanine fluorescence dyes, Cy3 and Cy5. Besides oligonucleotide,
      the proposed method can be generalized to other microarray formats with various
      biomolecules such as complementary DNA, protein, peptide, carbohydrate, tissue,
      or other small biomolecules. Also, it can be easily applied to other fluorescence
      dyes for further dye chemistry improvement. 

PMID- 24324960
TI  - A comparative analysis of biomarker selection techniques.
AB  - Feature selection has become the essential step in biomarker discovery from high
      dimensional genomics data. It is recognized that different feature selection
      techniques may result in different set of biomarkers, that is, different groups
      of genes highly correlated to a given pathological condition, but few direct
      comparisons exist which quantify these differences in a systematic way. In this
      paper, we propose a general methodology for comparing the outcomes of different
      selection techniques in the context of biomarker discovery. The comparison is
      carried out along two dimensions: (i) measuring the similarity/dissimilarity of
      selected gene sets; (ii) evaluating the implications of these differences in
      terms of both predictive performance and stability of selected gene sets. As a
      case study, we considered three benchmarks deriving from DNA microarray
      experiments and conducted a comparative analysis among eight selection methods,
      representatives of different classes of feature selection techniques. Our results
      show that the proposed approach can provide useful insight about the pattern of
      agreement of biomarker discovery techniques. 

PMID- 24324961
TI  - Gelucire based in situ gelling emulsions: a potential carrier for sustained
      stomach specific delivery of gastric irritant drugs.
AB  - Non steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed
      medications to the geriatric patients for the treatment of arthritis and other
      painful disorders. The major side effects of NSAIDs are related to their effects
      on the stomach and bowels. The present study concerns assessment of the potential
      of liquid in situ gelling emulsion formulations (emulgels) as patient compliant
      stomach specific sustained release carrier for the delivery of highly gastric
      irritant drug, Piroxicam. Emulgels were prepared, without using any emulgent, by
      mixing different concentrations of molten Gelucire 39/01 with low viscosity
      sodium alginate solution prepared in deionized water at 50 degrees C. CaCO3 was
      used as buoyancy imparting as well as crosslinking agent. Emulgels so prepared
      were homogenous, physically stable, and rapidly formed into buoyant gelled mass
      when exposed to simulated gastric fluid (SGF, pH 1.2). Drug release studies
      carried out in SGF revealed significant retardation (P < 0.05) of Piroxicam
      release from emulgels compared to conventional in situ gelling formulations
      prepared without Gelucire 39/01. Pharmacodynamic studies carried out in albino
      rats revealed significantly increased analgesic/anti-inflammatory response from
      in situ emulgels compared to conventional in situ gelling formulations. Further,
      in vivo toxicity studies carried out in albino rats revealed no signs of gastric
      ulceration upon prolonged dosing.

PMID- 24324962
TI  - Prolonged delivery of ciprofloxacin and diclofenac sodium from a polymeric fibre
      device for the treatment of periodontal disease.
AB  - In vitro analysis of drug release and antimicrobial activity of the coblended
      crosslinked polymeric fibre device (PFD) were investigated. The fibre loaded with
      ciprofloxacin and diclofenac sodium was comprised of alginate and glycerol
      crosslinked with barium cations. The pH dependent drug release was evident with
      ciprofloxacin and diclofenac sodium diffusing from the fibre at pH 4.0 compared
      to pH 6.8, where the fibre swelled and eroded resulting in zero-order drug
      release. Agar diffusion studies followed by minimum inhibitory assays were
      conducted to determine the antimicrobial activity of the device against
      Escherichia coli, Enterococcus faecalis, and Streptococcus mutans. The
      antimicrobial activity of the PFD was confirmed in both test assays against all
      test pathogens. The MIC ranges at pH 4.0 for E. coli, E. faecalis, and S. mutans
      were 0.5-0.8, 0.4-1.1, and 0.7-2.1 MUg/mL, respectively. At pH 6.8, similar
      efficacies (0.3-0.5 MUg/mL for E. coli and E. faecalis and 0.6-1.0 MUg/mL for S.
      mutans) were observed. The effect of varying the plasticizer and crosslinking ion
      concentration on drug release profile of the fibers was further elucidated and
      conceptualized using molecular mechanics energy relationships (MMER) and by
      exploring the spatial disposition of geometrically minimized molecular
      conformations.

PMID- 24324964
TI  - CYP19 genetic polymorphism haplotype AASA is associated with a poor prognosis in
      premenopausal women with lymph node-negative, hormone receptor-positive breast
      cancer.
AB  - Given the critical role of CYP19 in estrogen synthesis, we investigated the
      influence of CYP19 gene polymorphisms on the clinical outcome of lymph node- (LN
      ) negative, hormone receptor- (HR-) positive early breast cancers. Genotyping for
      the CYP19 polymorphisms rs4646 (A/C), rs1065779 (A/C), CYP19 (TTTA)n (short
      allele/long (S/L) allele using the 7 TTTA repeat polymorphism as the cut-off),
      and rs1870050 (A/C) was performed on 296 patients with LN-negative, HR-positive
      breast cancers. All patients received adjuvant hormonal therapy. Associations
      were examined between these 4 genotypes and 6 common haplotypes of CYP19 and
      distant disease-free survival (DDFS), disease-free survival (DFS), and overall
      survival (OS). Patients were divided into the 6 subhaplotypes of CCLA (41.1%),
      AASA (17.1%), CASA (11.9%), CCLC (8.9%), CCSA (7.5%), AASC (8.9%), and others
      (4.6%). In premenopausal patients, haplotype AASA was significantly associated
      with a poor DDFS (adjusted hazard ratio (aHR), 3.3; P = 0.001), DFS (aHR, 2.5; P
      = 0.0008), and OS (aHR, 2.9; P = 0.0004) after adjusting for age, tumor size,
      tumor grade, estrogen receptor status, progesterone receptor status,
      chemotherapy, pathology, adjuvant hormone therapy, menopausal status, and
      radiotherapy. Furthermore, haplotype AASA remained a negative prognostic factor
      for premenopausal patients receiving adjuvant chemotherapy in terms of DDFS (aHR,
      4.5; P = 0.0005), DFS (HR, 3.2; P = 0.003), and OS (HR, 6.4; P = 0.0009).
      However, in postmenopausal patients, haplotype AASA was not associated with a
      poor prognosis, whereas the AASC haplotype was significantly associated with a
      poor DFS (aHR, 3.1; P = 0.03) and OS (aHR, 4.4; P = 0.01). Our results indicate
      that, in patients with LN-negative, HR-positive breast cancers, genetic
      polymorphism haplotype AASA is associated with poor survival of premenopausal
      women but does not affect survival of postmenopausal women. 

PMID- 24324963
TI  - Tyrosine phosphorylation modulates the vascular responses of mesenteric arteries
      from human colorectal tumors.
AB  - The aim of this study was to analyze whether tyrosine phosphorylation in tumoral
      arteries may modulate their vascular response. To do this, mesenteric arteries
      supplying blood flow to colorectal tumors or to normal intestine were obtained
      during surgery and prepared for isometric tension recording in an organ bath.
      Increasing tyrosine phosphorylation with the phosphatase inhibitor, sodium
      orthovanadate produced arterial contraction which was lower in tumoral than in
      control arteries, whereas it reduced the contraction to noradrenaline in tumoral
      but not in control arteries and reduced the relaxation to bradykinin in control
      but not in tumoral arteries. Protein expression of VEGF-A and of the VEGF
      receptor FLT1 was similar in control and tumoral arteries, but expression of the
      VEGF receptor KDR was increased in tumoral compared with control arteries. This
      suggests that tyrosine phosphorylation may produce inhibition of the contraction
      in tumoral mesenteric arteries, which may increase blood flow to the tumor when
      tyrosine phosphorylation is increased by stimulation of VEGF receptors. 

PMID- 24324965
TI  - The association between dietary intake of folate and physical activity with
      psychological dimensions of depressive symptoms among students from Iran.
AB  - Depression in students is a major public health problem. Although several risk
      factors associated with depression have been identified, the cause of depression
      is still not clear. Several studies have demonstrated that physical activity and
      nutrient intake, such as increased levels of B vitamins in serum, decrease
      symptoms of depression. The aim of this study was to investigate the association
      between physical activity and dietary intake of vitamins B6, B9, and B12 and
      symptoms of depression among postgraduate students. The results of this study
      suggest that intake of vitamin B9 may modulate the total score of Center for
      Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D
      including depressive affect and interpersonal difficulties. This study also
      showed that moderate/high levels of physical activity were inversely and
      significantly associated with symptoms of depression (total scores) and three
      subscales of the CES-D including depressive affect, positive affect, and somatic
      complaints.

PMID- 24324966
TI  - A pH-sensitive, biobased calcium carbonate aragonite nanocrystal as a novel
      anticancer delivery system.
AB  - The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an
      effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of
      these nanocrystals displayed high levels of selectivity and specificity in
      achieving effective cancer cell death without nonspecific toxicity. These results
      confirmed that DOX was intercalated into calcium carbonate nanocrystals at high
      loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO3/DOX
      nanocrystals are relatively stable at neutral pH (7.4), resulting in slow
      release, but the nanocrystals progressively dissociated in acidic pH (4.8)
      regimes, triggering faster release of DOX. The CaCO3/DOX nanocrystals exhibited
      high uptake by MDA MB231 breast cancer cells and a promising potential delivery
      of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral
      red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that
      CaCO3/DOX nanocrystals are more sensitive and gave a greater reduction in cell
      growth than free DOX. Our findings suggest that CaCO3 nanocrystals hold
      tremendous promise in the areas of controlled drug delivery and targeted cancer
      therapy.

PMID- 24324968
TI  - Novel natural structure corrector of ApoE4 for checking Alzheimer's disease:
      benefits from high throughput screening and molecular dynamics simulations.
AB  - A major genetic suspect for Alzheimer's disease is the pathological conformation
      assumed by apolipoprotein E4 (ApoE4) through intramolecular interaction. In the
      present study, a large library of natural compounds was screened against ApoE4 to
      identify novel therapeutic molecules that can prevent ApoE4 from being converted
      to its pathological conformation. We report two such natural compounds PHC and
      IAH that bound to the active site of ApoE4 during the docking process. The
      binding analysis suggested that they have a strong mechanistic ability to correct
      the pathological structural orientation of ApoE4 by preventing repulsion between
      Arg 61 and Arg 112, thus inhibiting the formation of a salt bridge between Arg 61
      and Glu 255. However, when the molecular dynamics simulations were carried out,
      structural changes in the PHC-bound complex forced PHC to move out of the cavity
      thus destabilizing the complex. However, IAH was structurally stable inside the
      binding pocket throughout the simulations trajectory. Our simulations results
      indicate that the initial receptor-ligand interaction observed after docking
      could be limited due to the receptor rigid docking algorithm and that the
      conformations and interactions observed after simulation runs are more
      energetically favored and should be better representations of derivative poses in
      the receptor. 

PMID- 24324967
TI  - Asthma management in sickle cell disease.
AB  - Asthma is a common comorbid factor in sickle cell disease (SCD). However, the
      incidence of asthma in SCD is much higher than expected compared to rates in the
      general population. Whether "asthma" in SCD is purely related to genetic and
      environmental factors or rather is the consequence of the underlying hemolytic
      and inflammatory state is a topic of recent debate. Regardless of the etiology,
      hypoxemia induced by bronchoconstriction and inflammation associated with asthma
      exacerbations will contribute to a cycle of sickling and subsequent complications
      of SCD. Recent studies confirm that asthma predisposes to complications of SCD
      such as pain crises, acute chest syndrome, and stroke and is associated with
      increased mortality. Early recognition and aggressive standard of care management
      of asthma may prevent serious pulmonary complications and reduce mortality.
      However, data regarding the management of asthma in SCD is very limited. Clinical
      trials are needed to evaluate the effectiveness of current asthma therapy in
      patients with SCD and coincident asthma, while mechanistic studies are needed to
      delineate the underlying pathophysiology. 

PMID- 24324969
TI  - Cultivation-dependent assessment, diversity, and ecology of haloalkaliphilic
      bacteria in arid saline systems of southern Tunisia.
AB  - Haloalkaliphiles are polyextremophiles adapted to grow at high salt
      concentrations and alkaline pH values. In this work, we isolated 122
      haloalkaliphilic bacteria upon enrichments of 23 samples from 5 distinct saline
      systems of southern Tunisia, growing optimally in media with 10% salt and at pH
      10. The collection was classified into 44 groups based on the amplification of
      the 16S-23S rRNA internal transcribed spacers (ITS-PCR). Phylogenetic analysis
      and sequencing of the 16S rRNA genes allowed the identification of 13 genera and
      20 distinct species. Three gram-positive isolates showing between 95 and 96% of
      16S rRNA sequence homology with Bacillus saliphilus could represent new species
      or genus. Beside the difference in bacterial diversity between the studied sites,
      several species ecological niches correlations were demonstrated such as
      Oceanobacillus in salt crust, Nesterenkonia in sand, and Salinicoccus in the
      rhizosphere of the desert plant Salicornia. The collection was further evaluated
      for the production of extracellular enzymes. Activity tests showed that gram
      positive bacteria were mostly active, particularly for protease, lipase, DNase,
      and amylase production. Our overall results demonstrate the huge phenotypic and
      phylogenetic diversity of haloalkaliphiles in saline systems of southern Tunisia
      which represent a valuable source of new lineages and metabolites. 

PMID- 24324970
TI  - Immune modulation and stereotactic radiation: improving local and abscopal
      responses.
AB  - New and innovative treatment strategies for cancer patients in the fields of
      immunotherapy and radiotherapy are rapidly developing in parallel. Among the most
      promising preclinical treatment approaches is combining immunotherapy with
      radiotherapy where early data suggest synergistic effects in several tumor model
      systems. These studies demonstrate that radiation combined with immunotherapy can
      result in superior efficacy for local tumor control. More alluring is the
      emergence of data suggesting an equally profound systemic response also known as
      "abscopal" effects with the combination of radiation and certain immunotherapies.
      Studies addressing optimal radiation dose, fractionation, and modality to be used
      in combination with immunotherapy still require further exploration. However,
      recent anecdotal clinical reports combining stereotactic or hypofractionated
      radiation regimens with immunotherapy have resulted in dramatic sustained
      clinical responses, both local and abscopal. Technologic advances in clinical
      radiation therapy has made it possible to deliver hypofractionated regimens
      anywhere in the body using stereotactic radiation techniques, facilitating
      further clinical investigations. Thus, stereotactic radiation in combination with
      immunotherapy agents represents an exciting and potentially fruitful new space
      for improving cancer therapeutic responses. 

PMID- 24324971
TI  - Teratogenic potential of antiepileptic drugs in the zebrafish model.
AB  - The zebrafish model is an attractive candidate for screening of developmental
      toxicity during early drug development. Antiepileptic drugs (AEDs) arouse concern
      for the risk of teratogenicity, but the data are limited. In this study, we
      evaluated the teratogenic potential of seven AEDs (carbamazepine (CBZ),
      ethosuximide (ETX), valproic acid (VPN), lamotrigine (LMT), lacosamide (LCM),
      levetiracetam (LVT), and topiramate (TPM)) in the zebrafish model. Zebrafish
      embryos were exposed to AEDs from initiation of gastrula (5.25 hours post
      fertilization (hpf)) to termination of hatching (72 hpf) which mimic the
      mammalian teratogenic experimental design. The lethality and teratogenic index
      (TI) of AEDs were determined and the TI values of each drug were compared with
      the US FDA human pregnancy categories. Zebrafish model was useful screening model
      for teratogenic potential of antiepilepsy drugs and was in concordance with in
      vivo mammalian data and human clinical data. 

PMID- 24324972
TI  - Immune responses following stereotactic body radiotherapy for stage I primary
      lung cancer.
AB  - PURPOSE: Immune responses following stereotactic body radiotherapy (SBRT) for
      stage I non-small cell lung cancer (NSCLC) were examined from the point of view
      of lymphocyte subset counts and natural killer cell activity (NKA). PATIENTS AND
      METHODS: Peripheral blood samples were collected from 62 patients at 4 time
      points between pretreatment and 4 weeks post-treatment for analysis of the change
      of total lymphocyte counts (TLC) and lymphocyte subset counts of CD3+, CD4+,
      CD8+, CD19+, CD56+, and NKA. In addition, the changes of lymphocyte subset counts
      were compared between patients with or without relapse. Further, the correlations
      between SBRT-related parameters and immune response were analyzed for the purpose
      of revealing the mechanisms of the immune response. RESULTS: All lymphocyte
      subset counts and NKA at post-treatment and 1 week post-treatment were
      significantly lower than pre-treatment (P < 0.01). No significant differences in
      the changes of lymphocyte subset counts were observed among patients with or
      without relapse. The volume of the vertebral body receiving radiation doses of 3
      Gy or more (VV3) significantly correlated with the changes of nearly all
      lymphocyte subset counts. CONCLUSIONS: SBRT for stage I NSCLC induced significant
      immune suppression, and the decrease of lymphocyte subset counts may be
      associated with exposure of the vertebral bone marrow.

PMID- 24324973
TI  - In vitro manganese exposure disrupts MAPK signaling pathways in striatal and
      hippocampal slices from immature rats.
AB  - The molecular mechanisms mediating manganese (Mn)-induced neurotoxicity,
      particularly in the immature central nervous system, have yet to be completely
      understood. In this study, we investigated whether mitogen-activated protein
      kinases (MAPKs) and tyrosine hydroxylase (TH) could represent potential targets
      of Mn in striatal and hippocampal slices obtained from immature rats (14 days
      old). The aim of this study was to evaluate if the MAPK pathways are modulated
      after subtoxic Mn exposure, which do not significantly affect cell viability. The
      concentrations of manganese chloride (MnCl2; 10-1,000  MUM) caused no change in
      cell viability in slices exposed for 3 or 6 hours. However, Mn exposure
      significantly increased extracellular signal-regulated kinase (ERK) 1/2, as well
      as c-Jun N-terminal kinase (JNK) 1/2/3 phosphorylation at both 3 and 6 hours
      incubations, in both brain structures. Furthermore, Mn exposure did not change
      the total content or phosphorylation of TH at the serine 40 site in striatal
      slices. Thus, Mn at concentrations that do not disrupt cell viability causes
      activation of MAPKs (ERK1/2 and JNK1/2/3) in immature hippocampal and striatal
      slices. These findings suggest that altered intracellular MAPKs signaling
      pathways may represent an early event concerning the effects of Mn in the
      immature brain.

PMID- 24324974
TI  - Chitosan dermal substitute and chitosan skin substitute contribute to accelerated
      full-thickness wound healing in irradiated rats.
AB  - Wounds with full-thickness skin loss are commonly managed by skin grafting. In
      the absence of a graft, reepithelialization is imperfect and leads to increased
      scar formation. Biomaterials can alter wound healing so that it produces more
      regenerative tissue and fewer scars. This current study use the new chitosan
      based biomaterial in full-thickness wound with impaired healing on rat model.
      Wounds were evaluated after being treated with a chitosan dermal substitute, a
      chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin
      substitute showed the most re-epithelialization (33.2 +/- 2.8%), longest
      epithelial tongue (1.62 +/- 0.13 mm), and shortest migratory tongue distance
      (7.11 +/- 0.25 mm). The scar size of wounds treated with the chitosan dermal
      substitute (0.13 +/- 0.02 cm) and chitosan skin substitute (0.16 +/- 0.05 cm)
      were significantly decreased (P < 0.05) compared with duoderm (0.45 +/- 0.11 cm).
      Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the
      presence of human hair follicle stem cells and fibroblasts that were incorporated
      into and surviving in the irradiated wound. We have proven that a chitosan dermal
      substitute and chitosan skin substitute are suitable for wound healing in full
      thickness wounds that are impaired due to radiation. 

PMID- 24324975
TI  - Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of
      human pancreatic cancer.
AB  - Pancreatic cancer is a malignant neoplasm originating from transformed cells
      arising in tissues forming the pancreas. The best chemotherapeutic agent used to
      treat pancreatic cancer is the gemcitabine. However, gemcitabine treatment is
      associated with many side effects. Thus novel strategies involving less toxic
      agents for treatment of pancreatic cancer are necessary. Curcumin is one such
      agent that inhibits the proliferation and angiogenesis of a wide variety of tumor
      cells, through the modulation of many cell signalling pathways. In this study, we
      investigated whether curcumin plays antitumor effects in MIA PaCa-2 cells. In
      vitro studies showed that curcumin inhibits the proliferation and enhances
      apoptosis of MIA PaCa-2 cells. To test whether the antitumor activity of curcumin
      is also observed in vivo, we generated an orthotopic mouse model of pancreatic
      cancer by injection of MIA PaCa-2 cells in nude mice. We placed mice on diet
      containing curcumin at 0.6% for 6 weeks. In these treated mice tumors were
      smaller with respect to controls and showed a downregulation of the transcription
      nuclear factor NF-kappaB and NF-kappaB-regulated gene products. Overall, our data
      indicate that curcumin has a great potential in treatment of human pancreatic
      cancer through the modulation of NF-kappaB pathway.

PMID- 24324976
TI  - Proteomic identification of dengue virus binding proteins in Aedes aegypti
      mosquitoes and Aedes albopictus cells.
AB  - The main vector of dengue in America is the mosquito Aedes aegypti, which is
      infected by dengue virus (DENV) through receptors of midgut epithelial cells. The
      envelope protein (E) of dengue virus binds to receptors present on the host cells
      through its domain III that has been primarily recognized to bind cell receptors.
      In order to identify potential receptors, proteins from mosquito midgut tissue
      and C6/36 cells were purified by affinity using columns with the recombinant E
      protein domain III (rE-DIII) or DENV particles bound covalently to Sepharose 4B
      to compare and evaluate their performance to bind proteins including putative
      receptors from female mosquitoes of Ae. aegypti. To determine their identity mass
      spectrometric analysis of purified proteins separated by polyacrylamide gel
      electrophoresis was performed. Our results indicate that both viral particles and
      rE-DIII bound proteins with the same apparent molecular weights of 57 and 67 kDa.
      In addition, viral particles bound high molecular weight proteins. Purified
      proteins identified were enolase, beta-adrenergic receptor kinase (beta-ARK),
      translation elongation factor EF-1 alpha/Tu, and cadherin. 

PMID- 24324978
TI  - Implementing National System of Health Research Ethics Regulations: The Nigerian
      Experience.
AB  - Efforts by Nigerian authorities to institutionalize health research dates back to
      the early 70's with the establishment of the Medical Research Council.
      Subsequently efforts to strengthen a national health research system in line with
      the concept of Essential National Health Research (ENHR) were made but albeit un
      successfully. This may have been as a result of poor political support, and lack
      of regulations to promote health research in the country. However little is known
      about health research regulations and their implementation in Nigeria. Health and
      health research in Nigeria is not regulated via a set of clearly defined
      legislation. While the country has developed a regulation document for health
      research ethics, compliance to this document is likely to be affected by the lack
      of legislation in for the health system as an entity. In this paper we narrate
      the developments in health, health research, and health regulations; we describe
      process for, and extent of implementation of the National Code of Health Research
      Ethics. We conclude that several factors affect the extent of implementation of
      the ethics code amongst which legislation is an important one.

PMID- 24324977
TI  - Rotational transport of islets: the best way for islets to get around?
AB  - Islet transplantation is a valid treatment option for patients suffering from
      type 1 diabetes mellitus. To assure optimal islet cell quality, specialized islet
      isolation facilities have been developed. Utilization of such facilities
      necessitates transportation of islet cells to distant institutions for
      transplantation. Despite its importance, a clinically feasible solution for the
      transport of islets has still not been established. We here compare the
      functionality of isolated islets from C57BL/6 mice directly after the isolation
      procedure as well as after two simulated transport conditions, static versus
      rotation. Islet cell quality was assessed using real-time live confocal
      microscopy. In vivo islet function after syngeneic transplantation was determined
      by weight and blood sugar measurements as well as by intraperitoneal glucose
      tolerance tests. Vascularization of islets was documented by fluorescence
      microscopy and immunohistochemistry. All viability parameters documented
      comparable cell viability in the rotary group and the group transplanted
      immediately after isolation. Functional parameters assessed in vivo displayed no
      significant difference between these two groups. Moreover, vascularization of
      islets was similar in both groups. In conclusion, rotary culture conditions
      allows the maintenance of highest islet quality for at least 15 h, which is
      comparable to that of freshly isolated islets.

PMID- 24324979
TI  - A Viable and Simple Self-Sampling Method for Human Papillomavirus Detection among
      South African Adolescents.
AB  - BACKGROUND: Self-sampling for Human Papillomavirus (HPV) testing may offer
      improved patient acceptability, decreased cost, and greater practicality than
      clinician collection of specimens. HPV testing among adolescents is necessary to
      conduct vaccine surveillance and may play a role in cervical cancer screening
      among some populations. METHODS: A cross-sectional prevalence study was conducted
      to compare the results of self-collected and clinician-collected specimens for
      Human papillomavirus (HPV) testing among South African adolescent females. All
      participants provided self-sampled vaginal swabs and underwent clinician
      collection of cervical swabs for HPV DNA analysis. The level of agreement between
      HPV DNA results from the two specimen collection methods was measured. RESULTS:
      The level of agreement between HPV DNA results from self-collected and clinician
      collected specimens was high (kappa=86.7; p<0.001). A high prevalence of HPV
      overall was found by both specimen collection methods (57%; 95% CI 0.37-0.75).
      Low-risk HPV (LR-HPV) types were found slightly more frequently in self-collected
      specimens. CONCLUSION: There is a high level of agreement between the HPV DNA
      results from self-collected and clinician-collected specimens. Self-collection of
      specimens for HPV testing is a viable alternative among adolescents.

PMID- 24324980
TI  - The evolution of sputum cytometry to assess bronchitis.

PMID- 24324982
TI  - Multimorbidity.
AB  - As Australia's population ages, it is expected that the number of people with
      multiple chronic conditions (multimorbidity) will increase. Studies have shown
      that multimorbidity is associated with reduced quality of life for patients and
      increased demand on health resources, complexity of care and patient mortality.
      Similarly to many health care systems around the world, Australia's secondary and
      tertiary health care has a single disease focus (eg. diabetes mellitus or mental
      health). However, the complexity of care in managing patients with multiple
      chronic conditions, often with competing demands, is best handled in primary care
      by general practitioners (GPs). 

PMID- 24324981
TI  - When to suspect occupational asthma.
AB  - Occupational asthma (OA) is a difficult diagnosis to make. The present review
      describes the work environments in which workers are at risk for developing OA,
      the characteristics of the individuals in whom OA should be suspected and the
      investigation that can be performed to diagnose the condition. Accurately
      diagnosing OA is crucial because of the major social and economic consequences of
      this diagnosis on the patient. 

PMID- 24324983
TI  - 'If this..., then...' - Resource allocation in a finite world.
AB  - BACKGROUND: Tasks in general practice can be divided into three areas: acute
      care, planned secondary and tertiary prevention, and primary prevention. There is
      some evidence that the demands placed on practitioners by the second and third
      areas can decrease the time available for the first. OBJECTIVE: To assess the
      work load of general practitioners and the evidence around benefit for effort,
      and suggest some strategies for making the most of available time. DISCUSSION:
      Time wasting in general practice can be doctor-generated, role-generated or
      Medicare/government-generated. Doctor-generated time wasting includes doing
      things for which there is evidence of futility and may comprise investigations,
      screening and specific treatments. Appropriate workforce deployment can reduce
      role-generated time wasting. Medicare/government-generated waste occurs when
      there are financial incentives for health care providers to persist in activities
      with little evidence of benefit, or even evidence of no benefit. GPs need to
      actively plan to achieve a balance in providing care in the three areas of
      general practice.

PMID- 24324984
TI  - Multimorbidity: negotiating priorities and making progress.
AB  - BACKGROUND: Patients with multimorbidity are increasingly common in general
      practice. Multimorbidity is a challenge for both patients and practitioners
      because of the complexity of care and its impact on patients' lives. Single
      disease-based guidelines are of limited use to providers managing patients with
      multimorbidity. OBJECTIVE: The article aims to discuss how multimorbidity can be
      best managed in general practice. It does this within the framework of a patient
      centred approach that recognises the importance of finding common ground with
      patients in setting priorities and assessing the impact of care. DISCUSSION:
      Providing effective care for multimorbidity requires shared decision-making about
      goals with patients and more effective communication and coordination between
      providers. For this group of patients, our current single-disease-based models of
      care need to be replaced with more integrated ones in which the impact of all the
      patient's conditions on their quality of life are considered.

PMID- 24324985
TI  - Is the problem that everything is a diagnosis?
AB  - BACKGROUND: Overdiagnosis is the diagnosis of 'illnesses' that would never have
      caused patients harm but potentially exposes them to treat-ments where the risks
      outweigh the benefits. The problem of overdiagnosis is affecting an increasing
      proportion of the population. OBJECTIVE: Overdiagnosis is occurring in several
      different ways: by changes in the definition or threshold of disease, labelling
      of risk factors as diseases, early detection from both deliberate screening
      programs and incidental detection ('incidentalomas'), and the medicalisation of
      life, particularly in psychiatry. DISCUSSION: General practitioners often carry
      the burden of care for patients who have been overdiagnosed. It is important that
      general practi-tioners are aware of the potential harm of overdiagnosis,
      particularly through early detection and aggressive management of early disease.

PMID- 24324986
TI  - ACE inhibitor angioedema - a very late presentation.
AB  - The patient, a hypertensive man, 77 years of age, presented at a local rural
      hospital after noticing increasing swelling of his tongue, leading to difficulty
      talking and then difficulty breathing. These symptoms developed over about 2
      hours and he had not noted any rash. He had been on enalapril 10-20 mg for 23
      years. He had also been on hydrochlorothiazide and atorvastatin for some years.
      He had not taken any non-steroidal anti-inflammatory drugs (NSAIDs) before the
      swelling developed.

PMID- 24324987
TI  - Lump in the throat - a case study.
AB  - Jack, aged 66 years, presented to his general practitioner with a foreign body
      sensation in his throat and altered voice, which developed over 30 minutes. He
      was otherwise well, having no other new symptoms or recent alterations to
      medication. He had not eaten anything unusual. He had hypertension, type 2
      diabetes, stable ischaemic heart disease, urolithiasis and benign prostatic
      hypertrophy. His regular medication was metformin, rosuvastatin, carvedilol,
      candesartan (last 5 years) and saxagliptin (last 6 months). He had no allergies
      but was intolerant of ramipril due to cough. There was no family history of note.
      On examination he had no itch or rash, or swelling of the tongue, lips, cheek or
      neck. However, there was oedema of the soft palate and uvula. He was maintaining
      his airway, saturating at 98%, and his chest was clear. He was afebrile and
      systemically well.

PMID- 24324988
TI  - Post-operative wound management.
AB  - BACKGROUND: Optimal management of post-operative wounds in the community is
      important to prevent potential complications such as surgi-cal-site infections
      and wound dehiscence from developing. As such, general practitioners, who play an
      important part in the sub-acute management of post-operative wounds, should
      appreciate the physiology of wound healing and the principles of post-operative
      wound care. OBJECTIVE: The objective of this article is to update general
      practitioners on the important aspects of post-operative wound care. This
      includes a review of the physiology behind wound healing, an update on wound
      cleansing and dressing methods, as well as a guide on how common post-operative
      wound complications should be managed. DISCUSSION: The key elements of post
      operative wound care include timely review of the wound, appropriate cleansing
      and dressing, as well as early recognition and active treatment of wound
      complications.

PMID- 24324989
TI  - Evaluating squints in children.
AB  - BACKGROUND: Strabismus ('squint') is a common childhood disorder that can cause
      psychosocial distress and permanent functional disability. Early diagnosis is
      important to maximise visual rehabilitation and reduce the risk of amblyopia.
      There is currently no national Australian screening program for strabismus, which
      makes it important for all general practitioners (GPs) to master practical skills
      for evaluating this condition. GPs should also be aware of red flags in a history
      and examination that necessitate prompt investigation and management. OBJECTIVE:
      This article reviews practical screening tests to identify childhood strabismus,
      and discusses a framework for timely intervention. DISCUSSION: A comprehensive
      history is used to distinguish between primary and acquired strabismus. The four
      tests used to screen for stra-bismus are the light reflex test, the red reflex
      test, the cover test and the uncover test. Any child diagnosed with strabismus
      should be referred to an ophthalmologist for further assessment.

PMID- 24324990
TI  - Cutaneous indurated plaque on the abdomen associated with diabetes mellitus.
AB  - A woman, 74 years of age, presented to the emergency department with a lesion on
      the lower abdominal wall that had started a month earlier and was not associated
      with any other symptoms. Her family physician had treated it with emollient
      creams. Relevant past medical history included congestive heart failure,
      hypertension, hypertensive heart disease, pulmonary hypertension, mitral
      regurgitation, chronic atrial fibrillation, rosacea and diabetes mellitus that
      was being treated with oral hypoglycaemics (metformin). Physical examination
      revealed an area of skin on the lower abdominal wall that was ill-defined and
      indurated, with whitish papules and a 'cobblestone' appearance (Figure 1).

PMID- 24324991
TI  - Exercise for intermittent claudication and peripheral arterial disease.

PMID- 24324992
TI  - Human papillomavirus vaccine national catch-up program - insights into under
      notification.
AB  - BACKGROUND: We analysed human papillomavirus (HPV) vaccination coverage from the
      2007-2009 catch-up program for women aged 18-26 years by Division of General
      Practice (DGP), alongside a survey about under-notification. METHODS: Coverage
      rates were calculated from the National HPV Vaccination Program Register. An
      online survey of immunisation coordinators in DGP assessed under-notification.
      RESULTS: HPV vaccine coverage by DGPs varied greatly: dose 1, 22-70%; dose 2, 13
      60%; dose 3, 7-49%. Most coordinators (38/52, 66%) believed that more than 80% of
      practices notified the register. Perceived notification barriers included being
      busy, not knowing how to notify, not obtaining consent, insufficient remuneration
      and delay in register establishment. DISCUSSION: DGP coverage varied widely.
      Process barriers (time and resource limitations) probably contributed to under
      notification, with informational barriers (unaware how to notify) and
      motivational barriers (not worth the effort) secondary to this. Differences in
      reported coverage between DGPs and states reflect both differences in
      notification rates and underlying HPV vaccine coverage.

PMID- 24324993
TI  - Communication at the interface between hospitals and primary care - a general
      practice audit of hospital discharge summaries.
AB  - BACKGROUND: Timeliness and quality of hospital discharge summaries are crucial
      for patient safety and efficient health service provision after discharge.
      METHODS: We audited receipt rates, timeliness and the quality of discharge
      summaries for 49 admissions among 38 patients in an urban general practice. For
      missing discharge summaries, a hospital medical record search was performed.
      RESULTS: Discharge summaries were received for 92% of identified admissions; 73%
      were received within three days and 55% before the first post-discharge visit to
      the general practitioner (GP). Administrative information and clinical content,
      including diagnosis, treatment and follow-up plans, were well reported. However,
      information regarding tests, referrals and discharge medication was often
      missing; 57% of summaries were entirely typed and 13% had legibility issues.
      DISCUSSION: Completion rates were good but utility was compromised by delays,
      content omissions and formatting. Digital searching enables extraction of
      information from rich existing datasets contained in GP records for accurate
      measurement of discharge summary receipt rate and timing.

PMID- 24324994
TI  - Access to treatment for breast cancer-related lymphoedema in Australia.
AB  - BACKGROUND: The aim of this study was to describe availability of treatment for
      lymphoedema in Australia to enable physicians to manage patients with
      lymphoedema. METHODS: A validated questionnaire was sent to the Review and Survey
      Group of the Breast Cancer Network of Australia in May 2010 (n = 760) to
      investigate consumers' perspectives on treatment access. RESULTS: Responses were
      received from 444 women (58%) of whom 140 had received lymphoedema treatment in
      the previous 5 years. Barriers were encountered by 33% (n = 46). These barriers
      included access to a lymphoedema therapist (n = 34), treatment affordability (n =
      27), need to travel to access treatment (n = 21) and not knowing where to find
      help (n = 20). DISCUSSION: One-third of this group of women had difficulty
      accessing treatment to halt this potentially progressive condition. The general
      practitioner has an important role in detecting this condition, and advising
      where treatment can be accessed and which schemes might assist financially.

PMID- 24324995
TI  - English literacy as a barrier to health care information for deaf people who use
      Auslan.
AB  - BACKGROUND: This study sought to gain insight into how Deaf Australians who use
      Auslan as their primary language perceive their English literacy and if they feel
      that they can sufficiently access preventative and ongoing health care
      information, and to explore their views in regards to accessing information in
      Auslan. METHODS: A phenomenological, inductive study, with data collected through
      72 semi-structured interviews with Deaf Auslan users identified through non
      probabilistic, purposeful and network sampling. Data was thematically analysed
      for identification of issues related to healthcare information access through
      English. RESULTS: Deaf people experience barriers in accessing healthcare
      information because of limited English literacy and a lack of information being
      available in Auslan, apart from when Auslan interpreters are present in health
      care appointments. CONCLUSION: Many Deaf people in Australia lack consistent
      access to preventative and ongoing health care information. It is important to be
      aware of the English literacy levels of patients. More funding is needed for the
      provision of interpreting services in other healthcare contexts and the
      translation of materials into Auslan.

PMID- 24324996
TI  - Under the watchful eye of 'a benevolent dictator' - general practitioner and
      patient experiences of hepatitis C treatment initiation and shared-care in
      general practice.
AB  - BACKGROUND: Innovative models of hepatitis C treatment delivery are needed to
      increase treatment uptake. METHODS: A qualitative evaluation of the Australasian
      Society for HIV Medicine's Initiation of Hepatitis C Treatment in General
      Practice Pilot was conducted between November 2010 and June 2012. Structured
      interview schedules collected data on the treatment experiences of seven general
      practitioners (GPs) and eight of their patients. RESULTS: GPs were satisfied with
      the process of initiating hepatitis C treatment. They were generally positive
      about the support they had experienced under shared-care arrangements with
      tertiary clinics and they saw few barriers to initiating treatment. Similarly,
      patients appreciated the continuity of care that this treatment model affords,
      the convenience of accessing treatment from their GP and being treated by a GP
      they trusted. CONCLUSION: The initiation of hepatitis C treatment through general
      practice is a viable model that could increase the number of people accessing
      hepatitis C treatment.

PMID- 24324997
TI  - What do general practitioners think and do about prostate cancer screening in
      Australia?
AB  - BACKGROUND: Men seek advice from their general practitioner (GP) on the merits of
      screening for prostate cancer. This study aimed to examine how the knowledge and
      clinical experience of GPs influenced their position on prostate cancer
      screening. METHODS: A total of 13 focus groups were set up with 77 GPs. Focus
      group discussions were audio-taped and transcribed verbatim. Transcripts were
      analysed by two investigators via thematic analysis. RESULTS: GPs were evenly
      divided between those who proactively screen men for prostate cancer and those
      who do so only at the patient's request. GPs had limited knowledge of recently
      published evidence from trials on prostate cancer screening. DISCUSSION:
      Effective methods of increasing GP knowledge about evidence-based recommendations
      and potentially changing clinical behaviour are required in order to promote
      evidence-based decision-making by GPs and their patients.

PMID- 24324999
TI  - Real-time evaluation of aggregation using confocal imaging and image analysis
      tools.
AB  - Real-time confocal imaging was utilised to monitor the in situ loss of BSA
      monomers and aggregate formation using Spatial Intensity Distribution Analysis
      (SpIDA) and Raster Image Correlation Spectroscopy (RICS). At the proof of concept
      level this work has demonstrated the applicability of RICS and SpIDA for
      monitoring protein oligomerisation and larger aggregate formation. 

PMID- 24325000
TI  - reMelting curve analysis as a tool for enrichment monitoring in the SELEX
      process.
AB  - Current aptamer selection procedures enable limited control and transparency on
      how the DNA selection pool is evolving. Affinity tests and binding analyses are
      not always informative. Here we show that real-time PCR provides a valuable tool
      for the follow-up of aptamer selection. Limited time, work and amount of
      amplified ssDNA make this an interesting instrument to set-up a SELEX design and
      monitor the enrichment of oligonucleotides. reMelting Curve Analysis (rMCA) after
      reannealing under stringent conditions provides information about enrichment,
      compared to a random library. Monitoring the SELEX process and optimising
      conditions by means of the proposed methods can increase the selection efficiency
      in a controlled way. rMCA is applied in enrichment simulations and three
      different selection procedures. Our results imply that rMCA can be used for
      different SELEX designs and different targets. SELEX pool diversity analysis by
      rMCA has been proven to be a useful, reproducible tool to detect and evaluate
      enrichment of specific binding aptamers while the selection procedure is being
      performed. 

PMID- 24325001
TI  - A colorimetric and fluorometric dual-modal supramolecular chemosensor and its
      application for HSA detection.
AB  - A colorimetric and fluorometric dual-modal supramolecular chemosensor has been
      fabricated by using the H- and J-aggregates of a cyanine dye, which has been
      successfully applied to detect human serum albumin (HSA) in urine with high
      specificity. 

PMID- 24325002
TI  - A sensitive and visible fluorescence-turn-on probe for the CMC determination of
      ionic surfactants.
AB  - A sensitive and visible fluorescence-turn-on probe for the critical micelle
      concentration (CMC) determination of ionic surfactants has been developed based
      on practically no emission in micelles but strong aggregation-induced emission in
      solution of racemate tetrahydropyrimide THP-1. CMC values were determined via the
      inflexion with the strongest fluorescence intensity. 

PMID- 24325003
TI  - Enhancement of fluorescence intensity by silicon particles and its size effect.
AB  - Fluorescence-intensity enhancement of dye molecules was investigated using
      silicon submicron particles as a function of the particle size. Silicon particles
      with a size of 500 nm gave an enhancement factor up to 180. Measurement of
      scattering spectra revealed that the localized electric field at the particle
      enhances the fluorescence intensity. 

PMID- 24325004
TI  - Polymeric double-anion templated Er48 nanotubes.
AB  - A polymeric tube-like Er48 complex has been synthesized and structurally
      characterized, in which two types of anions, i.e. Cl(-) and NO3(-), template the
      formation of Er18 wheels and Er12 rings through hydrogen bonding, respectively. 

PMID- 24325005
TI  - Bis-sulfide bioconjugates for glutathione triggered tumor responsive drug
      release.
AB  - The reaction of bis-sulfone conjugation reagents with disulfide bonds allows the
      site-specific modification of various peptides and proteins. Herein, we present
      the intracellular disintegration of bis-sulfide containing somatostatin
      bioconjugates under controlled, tumor-relevant glutathione levels. GSH responsive
      release is demonstrated, which offers high potential for designing tumor
      responsive therapeutics. 

PMID- 24325006
TI  - Divorce among parents of children with autism: dispelling urban legends.

PMID- 24325007
TI  - [Indoor air guide values for acetaldehyde. Announcement of the German Ad-hoc
      Working Group on Indoor Guidelines of the Indoor Air Hygiene Committee and of the
      States' Supreme Health Authorities].
AB  - The German Ad-hoc Working Group on Indoor Guidelines of the Indoor Air Hygiene
      Committee and the States' Supreme Health Authorities is issuing indoor air guide
      values to protect public health. No suitable human studies are available for
      health evaluation of acetaldehyde in indoor air. In a well-documented subchronic
      inhalation animal study with rats assessed as reliable, local irritation effects
      were observed in nasal epithelia, most prominently in the olfactory epithelium
      with loss of olfactory neuronal cells. This study leads to a LOAEC of 48 mg
      acetaldehyde/m3 for continuous exposure for the endpoint nasal epithelium
      degeneration. By applying an interspecies factor of 1, a factor of 10 for
      interindividual variability, and a factor of 2 to account for the higher
      respiratory rate of children compared to adults, a health hazard guide value (RW
      II) of 1 mg acetaldehyde/m3 is obtained. A health precaution guide value (RW I)
      of 0.1 mg acetaldehyde/m3 is recommended.

PMID- 24325008
TI  - [Indoor air guide values for naphthalene and naphthalene-like compounds.
      Announcement of the German Ad-hoc Working Group on Indoor Guidelines of the
      Indoor Air Hygiene Committee and of the States' Supreme Health Authorities].
AB  - The German Ad-hoc Working Group on Indoor Guidelines of the Indoor Air Hygiene
      Committee and of the States' Supreme Health Authorities is issuing indoor air
      guide values to protect public health. Naphthalene is a potentially volatile two
      ring hydrocarbon with a mothball-like odor. Indoor air contaminations usually
      originate from tar-containing building products, sometimes from the use of
      mothballs. In Germany, indoor air concentrations of naphthalene are usually low,
      near the detection limit (medians of about 0.001 mg/m3, 95th percentiles up to
      0.004 mg/m3). Naphthalene-like volatile compounds have been defined to cover
      methyl- and dimethylnaphthalenes and tricyclic aromatic hydrocarbons (e.g.,
      acenaphthene, acenaphthylene, anthracene, fluorene and phenanthrene). Though
      methylnaphthalenes and dimethylnaphthalenes usually show low indoor air
      concentrations, they have been suspected to add to the mothball-like odor.
      Tricyclic aromatic hydrocarbons mostly occur below 0.001 mg/m3 of indoor air.
      Against this background naphthalene is seen to be the key component of this group
      of substances in indoor air. No valid human data is available with respect to
      health effects of inhaled naphthalene. Based on animal data cytotoxic
      inflammatory lesions in the rat nasal epithelium are regarded as the critical
      endpoint. In a subchronic inhalation study in rats (Dodd et al., Inhal Toxicol
      24:70-79, 2012), minimal effects were observed following an exposure to 5 mg
      naphthalene/m3. From this study the Ad-hoc Working Group derived a chronic NAEC
      of 2.5 mg naphthalene/m3. Time scaling was considered by a factor of 5.6
      extrapolating from 6 to 24 h and 5 to 7 days, a factor of 2 applied for the use
      of F344 rats instead of the more sensitive Sprague-Dawley rats. Incorporating an
      interspecies factor of 1, an intraspecies factor of 10 and a factor of 2 for
      insufficient data on the toxicity of naphthalene in children resulted in a
      precautionary value of 0.01 mg naphthalene/m3 and a hazard-based guide value of
      0.03 mg naphthalene/m3. In the European Union, naphthalene has been classified as
      a suspected human carcinogen. In rats, carcinogenicity (nasal olfactory
      neuroblastoma) was seen at 53 mg naphthalene/m3. In contrast no valid human data
      on carcinogenicity of naphthalene is available. The Ad-hoc Working Group holds
      that the derived guide values sufficiently prevent cytotoxic-inflammatory effects
      of naphthalene and consequently from its long-term impacts such as potential
      carcinogenicity. This opinion is supported by a study of Meng et al. (Mutat Res
      721:199-205, 2011) initially pointing to a missing primary genotoxicity of
      naphthalene. Only few data are available for health evaluation of naphthalene
      like compounds. Therefore, the indoor air guide values for naphthalene are
      recommended by the Ad-hoc Working Group to be used as preliminary indoor air
      guide values for the sum of bicyclic and tricyclic aromatic hydrocarbons, too.
      Indoor air measurement of tricyclic aromatic hydrocarbons should be restricted to
      the occurrence of directly emitting building products such as asphalt floor
      coverings.

PMID- 24325009
TI  - 2013 Prince Mahidol Award winners announced.

PMID- 24325010
TI  - Bhopal study represents "missed opportunity".

PMID- 24325011
TI  - [Refractive eye surgery: not appropriate for all refractive errors].

PMID- 24325014
TI  - [Fibrinolysis or primary angioplasty in infarction with ST segment elevation].

PMID- 24325015
TI  - [The implementation of a death with dignity program in an integral cancer
      center].

PMID- 24325016
TI  - [Analysis of circulating tumor deoxyribonucleic acid in the monitoring of
      metastatic breast cancer].

PMID- 24325017
TI  - Screening for glaucoma: U.S. Preventive Services Task Force Recommendation
      Statement.
AB  - DESCRIPTION: Update of the 2004 U.S. Preventive Services Task Force (USPSTF)
      recommendation on screening for glaucoma. METHODS: The USPSTF reviewed evidence
      on the benefits and harms of screening for glaucoma and of medical and surgical
      treatment of early glaucoma. Beneficial outcomes of interest included improved
      vision-related quality of life and reduced progression of early asymptomatic
      glaucoma to vision-related impairment. The USPSTF also considered evidence on the
      accuracy of glaucoma screening tests. POPULATION: This recommendation applies to
      adults who do not have vision symptoms and are seen in a primary care setting.
      RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to
      assess the balance of benefits and harms of screening for primary open-angle
      glaucoma in adults. (I statement)

PMID- 24325018
TI  - Pearls & Oy-sters: ictal syncope in a patient with temporal lobe epilepsy.

PMID- 24325019
TI  - Ultrasound as the first choice for peripheral nerve imaging?

PMID- 24325020
TI  - Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral
      oropharynx--part I: how.
AB  - OBJECTIVES/HYPOTHESIS: To revisit the surgical technique of lateral pharyngotomy
      in patients with selected, isolated, and untreated invasive squamous cell
      carcinoma of the lateral oropharynx. To describe postoperative management,
      complications, and functional outcomes. STUDY DESIGN: Retrospective review from a
      French university teaching hospital. METHODS: Ninety-one patients consecutively
      underwent lateral pharyngotomy for selected T1-T4 squamous cell carcinoma of the
      lateral oropharynx. RESULTS: Of the patients, 73.6% and 98.9% experienced an
      uncomplicated surgical and medical postoperative course, respectively. There were
      no intraoperative deaths, but a single patient died in the immediate
      postoperative period from carotid rupture following salivary oropharyngeal
      fistula. The most common significant complications were severe postoperative
      swallowing impairment, pneumonia from aspiration, and salivary oropharyngeal
      fistula noted in 6.5%, 4.3%, and 4.3% of cases, respectively. In univariate
      analysis, none of the variables under analysis was related to the various
      significant complications noted and/or to immediate postoperative death. No
      patient had a permanent tracheotomy, whereas one had a permanent gastrostomy. Of
      the patients in whom a full course of radiation therapy was delivered
      postoperatively, 13.6% developed a major complication. CONCLUSIONS: From a
      functional point of view, lateral pharyngotomy is a safe, reliable surgery with
      few major complications and might be considered a valuable alternative to
      chemoradiation and/or mandibulotomy for selected tumors of the lateral
      oropharynx.

PMID- 24325021
TI  - Newman government kills workers' comp.

PMID- 24325022
TI  - An attack on the very foundation of our profession.

PMID- 24325023
TI  - SA government proposes to limit homebirth practitioners.

PMID- 24325024
TI  - Mater requests meeting after protected industrial action.

PMID- 24325025
TI  - Paying for public services: the return of Robin Hood.

PMID- 24325026
TI  - Chief academic department administrator median compensation incentives by
      geographic section.

PMID- 24325027
TI  - Post-compliance, ICD-10 reimbursement issues.

PMID- 24325028
TI  - Sunshine law: don't be surprised by what is reported about your practice.

PMID- 24325029
TI  - [Retroperitoneal extraskeletal Ewing's sarcoma].

PMID- 24325030
TI  - [Comparison between covered and uncovered self-expandable metal stents in
      patients with malignant distal biliary obstruction].

PMID- 24325031
TI  - [The role of 18F-fluorodeoxyglucose positron emission tomography as a prognostic
      indicator for bile duct and gallbladder cancer: need for a prospective study
      using various quantitative parameters].

PMID- 24325032
TI  - ACHE is your career partner. ACHE provides a wealth of career management
      resources to meet your needs.

PMID- 24325033
TI  - Managing your career in transformative times.

PMID- 24325034
TI  - Aspirations of a servant leader.

PMID- 24325035
TI  - Five questions to get project stakeholder consensus.

PMID- 24325036
TI  - Generate success in your life: you are the leader of your own corporation.

PMID- 24325037
TI  - The ethics of mandatory flu shots. Balancing patient protection with healthcare
      worker autonomy is essential.

PMID- 24325038
TI  - Using huddles to enhance patient experience. Organizational huddles improve
      teamwork and patient care.

PMID- 24325039
TI  - Equal and respectful care for LGBT patients. The importance of providing an
      inclusive environment cannot be underestimated.

PMID- 24325040
TI  - The medicare inpatient hospital payment update.

PMID- 24325041
TI  - Leadership development the Baldrige way.

PMID- 24325042
TI  - Common sense, fortitude and discipline. Keys to creating a collaborative CEO
      board relationship.

PMID- 24325043
TI  - Improving care and health for low-income populations. Commonwealth Fund report
      highlights areas for improvement.

PMID- 24325044
TI  - A new spirit of service. Two "masters" describe the leadership competencies and
      imperatives for the health reform era.

PMID- 24325045
TI  - The path to chapter leadership. Chapter presidents share their success stories.

PMID- 24325046
TI  - [Ancient and modern application of aromatic herbs for activating yang in
      preventing and treating coronary heart disease angina].

PMID- 24325047
TI  - [Development and expectation of modernization of herbal medicines].
AB  - Natural herbs are useful by-products found by ancients when they searched and
      tasted natural vegetative foods. In the first century, herbal medicines had been
      much developed and independent academic systems had been established, as
      summarized separately in Chinese Shennong's Classics of Herbs and On Materia
      Medica written by Dioscorides of the Roman Empire. However, following rapid
      progress of modern science and technologies since Renaissance, clinical
      application of herbs was almost replaced by more effective artificial medicines
      in the West world, so the scientific research of herbs was almost abandoned. But
      in China, herbs are still constantly used by TCM physicians in their clinical
      practice and scientific studies for modernization of Chinese herbs have been
      carried out vigorously with attractive achievements since recent half of the last
      century. Therefore, the gap of herbal investigation and development in Western
      medicine will be successfully filled in by Chinese medical field.

PMID- 24325048
TI  - [Which research is needed to support clinical decision-making on integrative
      medicine? Can comparative effectiveness research close the gap?].
AB  - In clinical research on complementary and integrative medicine, experts and
      scientists have often pursued a research agenda in spite of an incomplete
      understanding of the needs of end users. Consequently, the majority of previous
      clinical trials have mainly assessed the efficacy of interventions. Scant data is
      available on their effectiveness. Comparative effectiveness research (CER)
      promises to support decision makers by generating evidence that compares the
      benefits and harms of best care options. This evidence, more generalizable than
      evidence generated by traditional randomized clinical trials (RCTs), is better
      suited to inform real-world care decisions. An emphasis on CER supports the
      development of the evidence base for clinical and policy decision-making. Whereas
      in most areas of complementary and integrative medicine data on CER is scarce,
      available acupuncture research already contributes to CER evidence. This paper
      will introduce CER and make suggestions for future research.

PMID- 24325049
TI  - [Diagnostic standard evaluation of Chinese medicine syndrome for coronary heart
      disease patients after percutaneous coronary intervention].
AB  - OBJECTIVE: To evaluate the validity, reliability, and clinical applicability of
      Chinese medicine syndrome diagnostic standards for coronary heart disease (CHD)
      patients after percutaneous coronary intervention (PCI), which was established by
      expert consultation. METHODS: A total of 1 050 CHD patients after PCI were
      recruited from 23 hospitals. The sensitivity, specificity, accuracy, positive
      likelihood ratio, and area under ROC curve were used to evaluate the validity of
      diagnostic standards for Chinese medical syndrome types. The observable agreement
      rate and Kappa value were used to evaluate the reliability. Positive predictive
      value and negative predictive value were used to evaluate the clinical
      applicability. RESULTS: The sensitivity, specificity, accuracy, positive
      likelihood ratio, area under ROC curve, observable agreement rate, Kappa value,
      positive predictive value, and negative predictive value of each Chinese medicine
      syndrome in CHD patients after PCI were as follows: 95.26%, 93.70%, 94.86%,
      15.13, 0.924, 98.76%, 0.969, 97.76%, and 87.24% for blood stasis syndrome;
      96.42%, 95.34%, 96.00%, 20.70, 0.957, 99.52%, 0.990, 97.02%, and 94.42% for qi
      deficiency syndrome; 88.19%, 96.46%, 94.19%, 24.89, 0.923, 96.67%, 0.915, 90.39%,
      and 95.58% for phlegm turbidity syndrome; 91.06%, 98.77%, 97.05%, 74.22, 0.950,
      98.67%, 0.960, 95.54%, and 97.46% for cardiac blood stasis syndrome; 98.41%,
      96.73%, 97.33%, 30.10, 0.976, 98.86%, 0.976, 94.40%, and 99.09% for qi deficiency
      blood stasis syndrome; 94.81%, 94.75%, 94.76%, 18.07, 0.948, 97.71%, 0.918,
      72.73%, and 99.20% for phlegm-stasis stagnation syndrome. CONCLUSION: The
      validity, reliability, and clinical applicability of Chinese medicine syndrome
      diagnostic standards for CHD patients after PCI were rational and considerable in
      clinical practice.

PMID- 24325050
TI  - [Association study between Chinese medicine blood stasis syndrome and TIMI risk
      stratification of patients with unstable angina pectoris].
AB  - OBJECTIVE: To study the correlation between thrombolysis in myocardial infarction
      (TIMI) risk stratification and blood stasis syndrome (BSS) score in patients with
      unstable angina pectoris (UAP), and to analyze the relation of BBS degree and UAP
      clinical outcomes. METHODS: Collected were general data, demographic data, risk
      factors, Chinese medical symptoms and syndromes, coronary artery angiography
      results, relevant physical and chemical examinations from 114 UAP inpatients.
      Gensini score, TIMI risk score, and BSS score of these patients were calculated.
      RESULTS: The BBS score and Gensini score were significantly positively correlated
      (r = 0.78, P < 0.01). The BBS score was significantly higher in those with lesion
      in three branches than those with lesion in one branch or in two branches (P <
      0.05). The BBS score was significantly higher in the high risk group than in the
      lower risk group and the medium risk group (P < 0.01). The TIMI risk score was
      obviously higher in the severe blood stasis group than in the moderate blood
      stasis group and the mild blood stasis group (P < 0. 05, P < 0.01). The BBS score
      and TIMI risk score was positively correlated (r = 0.23, P < 0.05). CONCLUSION:
      The BBS score was positively correlated with more coronary arteries involved. The
      more severe BBS degree, the TIMI risk score more higher, and the BBS degree more
      syndrome.

PMID- 24325051
TI  - [Effect of wenxin granule on plasma BNP and HRV of acute coronary syndrome
      patients].
AB  - OBJECTIVE: To observe the effect of Wenxin Granule (WG) on brain natriuretic
      peptide (BNP) and heart rate variability (HRV) of acute coronary syndrome (ACS)
      patients. METHODS: Totally 65 ACS patients were randomly assigned to the
      treatment group (35 cases) and the control group (30 cases). All patients were
      treated with routine therapies such as angiotensin conversing enzyme inhibitors
      (ACEI) and metoprolol. Those in the treatment group took WG, 9 g each time, three
      times daily. All were treated for 90 days. Plasma samples of BNP and HRV were
      determined before treatment and after treatment. RESULTS: There was no
      statistical difference in pre-treatment plasma BNP (P > 0.05). Plasma BNP
      significantly decreased after treatment in the two groups when compared with
      before treatment (P < 0.05). The decrease was more obvious in the treatment group
      (P < 0.05). There was no statistical difference in pre-treatment HRV (P > 0.05).
      Compared with before treatment in the same group, RMSSD, PNN50%, and high
      frequency (HF) obviously increased, while low frequency (LF) and LF/HF ratio
      significantly decreased in the two groups, showing statistical difference (P <
      0.05). The aforesaid indices were obviously better in the treatment group than in
      the control group (P < 0.05). CONCLUSION: Additional administration of WG could
      improve short-term clinical prognosis by down-regulating plasma BNP level (via
      improving myocardial ischemia) and modulating HRV.

PMID- 24325052
TI  - [Thread-moxa in Zhuang folk medicine combined with acupuncture and external
      application drugs on AIDS patients with herpes zoster: a clinical observation].
AB  - OBJECTIVE: To observe the efficacy of thread-moxa in Zhuang folk medicine (TM)
      combined with acupuncture and external application drugs for AIDS patients with
      herpes zoster (AHZ). METHODS: A randomized, controlled clinical trial was
      conducted in 60 patients with AHZ. They were randomly assigned to the treatment
      group (treated with TM combined with acupuncture and Jingwanhong Scald Ointment)
      and the control group (treated with Famciclovir Tablet, nimesulide dispersible
      tablet, vitamin B1, ribavirin ointment). The treatment course was 14 days for
      both groups.The clinical efficacy, significant efficiency visual analog scale
      score (VAS), sleep quality score (QS), the postherpetic neuralgia rate in 1 year
      after treatment were observed. RESULTS: The markedly effective rate was
      significantly higher in the treatment group than in the control group (86.7% vs.
      53.3%, P < 0.01). There was no statistical difference in the total effective rate
      between the two groups (96.7% vs. 80.0%, P > 0.05). The post-treatment VAS, QS,
      the time for pain disappearance, skin repair, crusting, and 1-year postherpetic
      neuralgia incidence rate were significantly lower in the treatment group than in
      the control group (P < 0. 05, P < 0.01). CONCLUSIONS: TM combined with
      acupuncture and Jingwanhong Scald Ointment was effective for treating AHZ
      patients. It relieved pain quickly, shortened their course of disease, and
      improved their quality of sleep.

PMID- 24325053
TI  - [Treating early-to-middle stage nontraumatic osteonecrosis of femoral head
      patients by jianpi huogu recipe: a retrospective study].
AB  - OBJECTIVE: To observe the efficacy and features of treating early-to-middle stage
      nontraumatic osteonecrosis of femoral head (NONFH) patients by Jianpi Huogu
      Recipe (JHR). METHODS: Using retrospective paired control method, early-to-middle
      stage NONFH patients treated by JHR and followed-up for 2 years were recruited as
      the test group (47 cases). Those accepted surgery of core decompression, focus
      debridement and bone graft were recruited as the control group (48 cases).
      Radiographic images and clinical data of patients were collected before and after
      treatment. The stable rate and excellent rate of Harris score were taken as
      efficacy evaluation indicators. RESULTS: (1) There was no statistical difference
      in excellent rate of Harris score between the two groups (95.74% vs. 79.17%, P >
      0.05). But better effects were obtained in the test group in relieving pain,
      improving joint deformation, joint mobility, and total Harris score (P < 0. 05, P
      < 0. 01). There was no statistical difference in the stable rate of radiography
      between the two groups (74.47% vs. 75.00%, P > 0.05). (2) There was no
      statistical difference in the stable rate of radiography at phase II and Ill
      [staging by Association Research Circulation Osseous (ARCO)] between the two
      groups (82.05% vs. 80.00%, 37.50% vs. 50.00%, P > 0.05). (3) The stable rate of
      radiography and excellent rate of Harris score were obviously higher in ARCO
      phase II patients than in ARCO phase Il patients (82.05% vs. 37.50%,97.44% vs.
      87.50%, P < 0.01). CONCLUSIONS: Equivalent stable rate of radiography to that of
      surgery could be obtained in treating early-to-middle stage NONFH patients by
      JHR. But it was better than surgery in relieving pain, improving joint
      deformation and joint mobility.

PMID- 24325054
TI  - [Latent structure model evaluation of syndrome elements and features in 826
      hypertriglyceridemia patients].
AB  - OBJECTIVE: To evaluate main Chinese medical syndrome elements and features of
      hypertriglyceridemia patients. METHODS: Using latent structure model (LSM)
      method, the latent structure diagram of 826 hypertriglyceridemia patients were
      established. Hypertriglyceridemia syndrome elements and features were interpreted
      by using latent probability, conditional probability, mutual information, and
      cumulative information coverage to quantify symptoms/syndromes data,as well as
      using manual interpretation methods. RESULTS: The accumulative information
      coverage rate reaching 95% was taken as the judgment standard for major syndrome
      elements. In the 826 hypertriglyceridemia patients, moderate and severe
      symptoms/syndromes (with the latent probability being 35% and 60% respectively)
      were dominant. The syndrome elements mainly included qi deficiency, qi
      stagnation,fire heat, stasis blood, yin deficiency, and yang deficiency. The main
      targets were dominated in Xin, Gan, and Shen. CONCLUSION: LSM based syndrome
      element evaluation method could quantify the association degree of each variable
      (syndrome element; Chinese medical symptoms) and the occurrence probability.

PMID- 24325055
TI  - [Discriminatory analyses of climacteric syndrome patients of shen deficiency
      syndrome].
AB  - OBJECTIVE: To find out a set of practical,objective, and quantitative laboratory
      indices of climacteric syndrome (CS) patients of Shen deficiency syndrome (SDS),
      thus studying the essence of SDS from the perspective of laboratory medicine.
      METHODS: Recruited were 40 CS patients of SDS (or of SDS as main syndrome) as the
      SDS group, while another 40 healthy subjects were recruited as the control group.
      Their serum samples were collected. Serum levels of total triiodothyronine (TT3),
      total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid
      stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), testosterone (TESTO), estradiol (E2), prolactin (PRL), progesterone
      (PROG), cortisol (CORT), immunoglobulin M (IgM), immunoglobulin G (lgG),
      Complement 3 (C3), complement hemolysis 50% (CH50), angiotensin converting enzyme
      (ACE), aldosterone (ALD), serum alkaline phosphatase (ALP), and bone Gla-protein
      (BGP) were measured by automatic electrochemical luminescence assay analyzer,
      automatic chemiluminescence assay analyzer, automatic biochemistry analyzer, and
      automatic enzyme-linked immunosorbent assay (ELISA) analyzer. The correlation
      between syndrome types and laboratory indices were judged by gradual discriminant
      analyses. RESULTS: (1) Compared with the control group,serum levels of CORT,
      TESTO, E2, TT3, FT3, FT4, TSH, C3, CH50, ALP, and BGP significantly decreased in
      the SDS group (P < 0.01, P < 0. 05), while FSH, LH, and ACE significantly
      increased (P < 0.05). (2) The index with stronger capacity for diagnosing CS
      patients of SDS was ranked from high to low as CH50, PROG, TSH, TESTO, BGP, CORT,
      and C3, with their contribution rate of the discriminant function being 95.9%.
      (3) Discriminant analysis equation of CS patients of SDS was Y = -25.904 -
      0.468CH50 + 0.002PROG + 0.182TSH + 9.690TESTO + 1.015BGP + 0.016CORT + 33.581 C3.
      CONCLUSIONS: (1) CS patients of SDS were closely correlated with thyroid
      hypothalamus-pituitary-adrenal axis, hypothalamus-pituitary-adrenal axis, renin
      renin-angiotensin-aldosterone system,the immune function, and bone formation, and
      etc. (2) CH50 might be of a high sensibility marker for diagnosing CS patients of
      SDS. (3) Discriminant analysis equations of laboratory medicine index may be used
      in preliminary diagnosis and auxiliary certificate of CS patients of SDS.

PMID- 24325056
TI  - [Research on the relationship between chinese medical syndrome types and Th1/Th2
      in bronchioloalveolar carcinoma by thoracoscopic technique].
AB  - OBJECTIVE: To study the relationship between Chinese medical syndrome types of
      bronchioloalveolar carcinoma (BAC) and Th1/Th2. METHODS: Totally 60 BAC patients
      were syndrome typed as qi and yin deficiency syndrome (QYDS) and qi stagnation
      and phlegm-blood stasis syndrome (QSPSS), 30 cases in each group. Meanwhile, 30
      subjects with benign pulmonary nodules were recruited as the control group. The
      contents of interferon-gamma (INF-gamma), interleukin 4 (IL-4), IL-2, and IL-5
      were detected using thoracoscopic technique. RESULTS: As for Th1 (INF-gamma and
      IL-2), it was ranked from high to low as the control group > the QSPSS group >
      the QYDS group (P < 0.05). As for Th2 (IL-4 and IL-5), it was ranked from high to
      low as the QYDS group > the QSPSS group >the control group (P < 0.05). As for
      Th1/Th2 (INF-gamma/lL-4, IL-2/IL-5), it was ranked from high to low as the
      control group > the QSPSS group >the QYDS group (P < 0.05). CONCLUSIONS: Compared
      with the tissue of benign nodules, Th1 function in tumor tissue of BAC patients
      was weaker and Th2 function stronger. Chinese medical syndrome types of BAC had
      correlation with Th1/Th2. Patients of excess syndrome had stronger immunity with
      Th1/Th2 shifting left,while those of deficiency syndrome were predispose to
      humoral immunity with Thl/Th2 shifting right.

PMID- 24325057
TI  - [Treating cervical spinal canal stenosis by open-door cervical laminoplasty
      combined modified buyang huanwu decoction].
AB  - OBJECTIVE: To explore the clinical efficacy of open-door cervical laminoplasty
      combined Modified Buyang Huanwu Decoction (MBHD) to treat cervical spinal canal
      stenosis (CSCS). METHODS: Totally 32 CSCS patients were randomly assigned to two
      groups, Group A (17 cases, treated by laminoplasty) and Group B (15 cases,
      treated by laminoplasty combined MBHD). All patients received open-door cervical
      laminoplasty. Those in Group B took MBHD additionally for 2 weeks after surgery.
      The visual analogue scale (VAS), the Japanese Orthopedic Association (JOA) score,
      and the neck disability index (NDI) were measured preoperative, postoperative 3
      months and 12 months, respectively. RESULTS: There was no statistical difference
      in preoperative VAS, JOA, or NDI (P > 0.05). The VAS, JOA, and NDI were obviously
      improved 3 months and 12 months after surgery in the two groups, showing
      statistical difference when compared with before surgery in the same group (P <
      0.01). At 3 months after surgery the aforesaid indices in Group B were superior
      to those in Group A (P < 0.05). There was no statistical difference in the
      aforesaid indices between the two groups at 12 months after surgery (P > 0.05).
      CONCLUSION: MBHD favorably improved early recovery of neural functions of CSCS
      patients (3 months after surgery).

PMID- 24325058
TI  - [The relationship between asthma patients with abnormal Savda in Uyghur medicine
      and the gene polymorphism of IL-4].
AB  - OBJECTIVE: To explore the relationship between the asthmatic Uyghur patients with
      abnormal Savda in Xinjiang and the gene polymorphism of interleukin-4 (IL-4).
      METHODS: Totally 76 asthmatic patients were syndrome typed according to the body
      fluid theory of Uyghur medicine. Among them, there were 30 asthmatic patients
      with abnormal Savda and 46 asthmatic patients without abnormal Savda. A
      comparison study was performed in 89 healthy individuals (as the healthy control
      group). The gene polymorphism of IL-4 promoter area-589 (C/T) site were detected
      by using PCR-RFLP. RESULTS: The distribution rate of genotype CT in asthmatic
      patients with abnormal Savda was significantly higher than that of the asthmatic
      patients with non-abnormal Savda and the healthy control group (P < 0.01). The
      distribution rate of genotype CT in asthmatic patients with non-abnormal Savda
      group was significantly higher than that of the healthy control group (P < 0.05).
      There was no difference in the distribution frequency of genotype CC or TT, or in
      the distribution frequency of allele C and T among the three groups (P > 0.05).
      CONCLUSION: Asthma in Uyghur patients with abnormal Savda in Xinjiang might be
      correlated to the gene polymorphism of IL-4 promoter area-589 (C/T).

PMID- 24325059
TI  - [Effect of bufalin combined gefitinib on lung cancer H1975 cells and its
      mechanisms research].
AB  - OBJECTIVE: To observe the effect of bufalin combined Gefitinib on lung cancer
      H1975 cells, and to explore its potential mechanisms for anti-tumor. METHODS: The
      cytostatic effects of bufalin (1 -100 nmol/L), gefitinib (0.1-20 micromol/L), and
      bufalin plus gefitinib on H1975 cells were evaluated by MTT assay. Their effects
      on apoptosis of H1975 cells were determined by flow cytometry (FCM). Their
      effects on expressions of epidermal growth factor receptor (EGFR) and Met signal
      pathway related proteins in H1975 cells were detected by Western blot. RESULTS:
      Results of MTT assay showed that gefitinib over 5 micromol/L could inhibit H1975
      cells. But combined therapy of bufalin and gefitinib could potently inhibit the
      growth of H1975 cells. Results of FCM showed the apoptotic rate was 61.64% +/-
      5.61% in the bufalin plus gefitinib group, obviously higher than that of the
      bufalin group (18.34% +/- 3.42%) and the gefitinib group (7.32% +/- 1.08%),
      showing statistical difference (P < 0.01). Results of Western blot showed the
      protein expressions of p-EGFR, p-Met, p-Akt, and p-mTOR in H1975 cells could be
      markedly down-regulated by bufalin plus gefitinib. CONCLUSIONS: Combination of
      bufalin and gefitinib potently inhibited the growth of H1975 cells, and induced
      cell apoptosis. The potential mechanism for anti-tumor might be involved in
      blocking EGFR-PI3k/Akt pathway.

PMID- 24325060
TI  - [Effect of yifei qinghua granule on VEGF, bFGF, angiostatin, and endostatin in
      Lewis lung cancer mice: an experimental study].
AB  - OBJECTIVE: To observe the effect of Yifei Qinghua Granule (YQG) on vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      angiostatin, and endostatin in tumor tissue of Lewis Lung cancer mice, and to
      explore its anti-tumor mechanisms. METHODS: Totally 70 C57BL/6 mice were randomly
      divided into the model group, the low, medium, and high dose YQG groups, the
      gefitinib group, the gefitinib plus medium dose YQG group, and the
      cyclophosphamide (CTX) group, 10 in each group. The models were established by
      subcutaneously injecting Lewis lung cancer cells from the right axilla of C57BL/6
      mice. Mice in the model group were given with 0.4 mL pure water by gastrogavage,
      once daily. Mice in the low and medium dose YHG groups were given with YHG at the
      daily dose of 5 and 10 g/kg by gastrogavage, once daily. Those in the high dose
      YHG group were given with YHG at 10 g/kg by gastrogavage, twice daily. Those in
      the gefitinib group were given with gefitinib 100 mg/ kg by gastrogavage, once
      daily. Those in the gefitinib plus medium dose YHG group were given with
      gefitinib at 100 mg/kg by gastrogavage in the morning and YHG at 10 g/kg by
      gastrogavage in the afternoon. All medication was started from the 2nd day of
      inoculation, lasting 14 successive days. Those in the CTX group were given CTX at
      60 mg/kg by peritoneal injection on the 3rd and the 7th day of the experiment.
      Mice were sacrificed at the fifteenth day of the experiment. Tumors were taken
      out. Expressions of VEGF, bFGF, angiostatin, and endostatin in the tumor tissue
      were detected using immunohistochemical assay. RESULTS: Compared with the model
      group, the expression of VEGF significantly decreased, expressions of angiostatin
      and endostatin significantly increased in each group (P < 0.01). The expression
      of bFGF significantly decreased in the gefitinib group (P < 0.05). There was no
      statistical difference in VEGF among all groups (P > 0.05). The angiostatin
      expression was significantly higher in the CTX group than in the low dose YQG
      group (P < 0.01). The expression of endostatin was significantly higher in the
      high dose YQG group and the gefitinib plus medium dose YQG group than in the low
      and the medium dose YQG groups (P < 0.01). The expression of endostatin was
      significantly higher in the gefitinib plus medium dose YQG group than in the
      gefitinib group (P < 0.05). CONCLUSION: The action mechanism of YQG in treating
      lung cancer might be achieved through reducing the expression of angiogenesis
      promoting factor VEGF and increasing expressions of angiogenesis inhibitors
      angiostatin and endostatin.

PMID- 24325061
TI  - [Radiosensitization effect of black garlic extract on lung cancer cell line Lewis
      cells].
AB  - OBJECTIVE: To explore the radiosensitization effect of black garlic extract (BGE)
      on lung cancer cell line Lewis cells. METHODS: The inhibition rate of lung cancer
      cells after BGE action was detected by MTT. Effect of BGE combined radiotherapy
      on the colony formation rate was observed by cloning formation assay. Changes of
      the cell morphology were observed by Hoechst staining. Changes of the cell cycle
      were detected by flow cytometry. Real time PCR was used to detect mRNA
      expressions of bcl-2 and bax. RESULTS: BGE could have significant inhibitory
      action on the growth of lung cancer Lewis cells. The combination of BGE and
      radiotherapy (by 60Co gamma) significantly induced Lewis cells' apoptosis in G2/M
      stage, obviously decreased the expression of bcl-2, and up-regulated the
      expression of bax. CONCLUSIONS: BGE could sensitize the lung cancer Lewis cells
      to ionizing irradiation. This effect might be probably caused by changing the
      cell cycles and affecting expressions of bax and bcl-2.

PMID- 24325062
TI  - [Effect of jianpi liqi recipe on mRNA expressions of TP, DPD, and CYP3A4 in mice
      with human gastric cancer transplanted tumor].
AB  - OBJECTIVE: To study the effect of Jianpi Liqi Recipe (JLR) on 5-fluorouracil (5
      FU) relevant metabolic enzymes and CYP3A4 (the same enzyme of many
      chemotherapeutics) of mice with human gastric cancer transplanted tumor. METHODS:
      Totally 80 mice were randomly divided into the model group, the chemotherapy
      group, the JLR group, and the combination group (using chemotherapy combined
      JLR), 20 in each group. The human gastric cancer transplanted tumor mouse model
      was duplicated by hypodermic inoculating MKN-8 tumor cell suspension from the
      left armpit. Physiological saline or JLR was given to those in the model group or
      the JLR group at 0.25 mL each time, twice daily by gastrogavage from the 2nd day
      after transplantation. Mice in the chemotherapy group were given 0.25 mL
      physiological saline, twice daily by gastrogavage 2 days after transplantation,
      for 5 days in succession, and then they were peritoneal injected with 5-FU at the
      daily dose of 20 mg/kg, once daily for 5 days in succession from the 7th day of
      transplantation. Those in the combination were given 0.25 mL JLR, twice daily by
      gastrogavage, for 5 days in succession, and then they were peritoneal injected
      with 5-FU at the daily dose of 20 mg/kg, once daily for 5 days in succession from
      the 7th day of transplantation. The mRNA expressions of thymidine phosphorylase
      (TP), dihydropyrimidine dehydrogenase (DPD), and CYP3A4 were detected using RT
      PCR. RESULTS: Compared with the model group and the chemotherapy group, mRNA
      expressions of TP and CYP3A4 obviously increased, mRNA expression of DPD
      obviously decreased in the JLR group and the combination group (P < 0.01). There
      was no statistical difference in mRNA expressions of TP, DPD, and CYP3A4 between
      the JLR group and the combination group (P > 0.05). CONCLUSION: JLR could promote
      the activation of 5-FU, suppress the decomposition and inactivation of 5-FU in
      the tumor tissue of mice, and improve the chemotherapeutic efficacy through up
      regulating mRNA expressions of TP and CYP3A4, and suppressing the mRNA expression
      of DPD.

PMID- 24325064
TI  - [Protection of huanglian jiedu decoction on livers of hyperlipidemia mice].
AB  - OBJECTIVE: To observe the protection of Huanglian Jiedu Decoction (HJD) on high
      fat diet induced liver damage mice [hyperlipidemic mice lacking apolipoprotein E
      (ApoE(-/-))]. METHODS: Wild type mice were divided into the wild common food
      group and the wild hyperlipidemia group. ApoE(-/-) mice were divided into the
      ApoE(-/-) common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/
      ) hyperlipidemia plus HJD group, 5 in each group. In the present study, wild type
      mice and homozygous apoE(-/-) mice were fed with a chow diet or a high
      cholesterol Western diet for 4 weeks. HJD at the daily dose of 5 g/kg was given
      to mice in the ApoE(-/-) hyperlipidemia plus HJD group by gastrogavage. The
      plasma levels of total cholesterol (TC), triglyceride (TG), low density
      cholesterol protein (LDL-C) were detected. The pathohistological changes of the
      liver were observed by Eosin and Hematoxylin (HE) staining. The liver macrophages
      and their subtype ratios, as well as macrophage surface receptor CD206 and CD36
      were detected by flow cytometry. RESULTS: Typical pathological changes of simple
      fatty liver were manifested in the ApoE(-/-) hyperlipidemia group, TC, TG, and
      LDL-C increased, the macrophage ratio increased, the expression level of
      macrophage surface receptor CD206 decreased, showing statistical difference when
      compared with the ApoE(-/-) common food group (P < 0.01, P < 0.05). The ratio of
      alternatively activated macrophages (M2) subpopulations was lower in the ApoE(-/
      ) hyperlipidemia group than in the wild common food group (P < 0.05). There was
      no obvious change in the expression level of CD36. After intervened by HJD for 4
      weeks, there was no obvious improvement in blood lipids. But the ratio of CD206+
      M2 macrophages was significantly improved, when compared with the ApoE(-/-)
      hyperlipidemia group (P < 0.05). The pathological changes of fatty liver were
      significantly attenuated. CONCLUSIONS: The liver protection effect of HJD might
      be associated with immunoregulation of M2 macrophage subpopulations and injured
      tissue repairmen. Its immunoregulation and liver protection were independent from
      lipids lowering.

PMID- 24325063
TI  - [Curcumin inhibited hypoxia induced epithelial-mesenchymal transition in hepatic
      carcinoma cell line HepG2 in vitro].
AB  - OBJECTIVE: To explore effects and possible mechanisms of curcumin on hypoxia
      induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cell
      line HepG2. METHODS: HepG2 cells were divided to 3 groups, i.e., the normal
      control group, the CoCl2 group, and the CoCl2 plus 10 micromol/L curcumin group.
      The proliferation of HepG2 was determined using MTT assay. The migration of HepG2
      was detected by wound healing assay.The mRNA expression of hypoxia-inducible
      factor-1 (HIF-1alpha) was evaluated with real-time RT-PCR. The protein
      expressions of HIF-1alpha, epithelial-cadherin (E-cadherin), and vimentin were
      determined using Western blot. RESULTS: Compared with the normal control group,
      the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia
      significantly increased, the expression of HIF-1alpha was up-regulated, and the
      expression of E-cadherin protein was obviously down-regulated, and the expression
      of vimentin significantly increased (all P < 0.05). Intervention by curcumin
      significantly inhibited the proliferation and migration of hypoxic HepG2 cells,
      and expressions of HIF-1alpha and vimentin decreased, and the expression of E
      cadherin was up-regulated, showing statistical difference when compared with
      those of the CoCl2 group (P < 0.05). There was no statistical difference in HIF
      1alpha mRNA expression among the 3 groups (P > 0.05). CONCLUSION: Curcumin could
      reverse the proliferation and migration of HepG2 cells under CoCl2-induced
      hypoxia condition, which might be associated with inhibiting up-regulated
      expressions of HIF-1alpha protein and EMT.

PMID- 24325065
TI  - [Effect of ningdong granule on stereotyped behaviors in Tourette syndrome model
      rats of different Chinese medical syndromes].
AB  - OBJECTIVE: To observe the effect of Ningdong Granule (NDG) on stereotyped
      behaviors in Tourette's syndrome (TS) model rats of different Chinese medical
      syndromes. METHODS: Thirty-two Wistar rats were used to establish TS models of
      different Chinese medical syndromes (n =8) induced by TS children patients' sera
      of 4 syndromes, i.e., Xin-Gan deficiency syndrome (XGDS), Gan-Shen yin deficiency
      syndrome (GSYDS), sputum-turbid blocking aperture syndrome (STBAS), and Gan
      hyperactivity Pi deficiency syndrome (GHPDS). Corresponding sera was micro
      infused to them while administering NDG (120 mg/kg each time, thrice daily, for 3
      successive weeks). Besides, another normal control group (n =8) was set up by
      injecting sera from healthy children plus intragastric perfusion of normal
      saline. Stereotyped behaviors were recorded on the 1st, 7th, 14th, and 21st day
      after administration of NDG. RESULTS: The anti-neural antibody serum
      concentration in TS children was significantly higher than that in healthy
      control [(1.28 +/- 0.36) UL vs. (0.52 +/- 0.24) U/L, P < 0.01 ]. It was (1.34 +/-
      0.41) U/L in the XGDS group, (1.19 +/- 0.51) U/L in the GSYDS group, (1.29 +/-
      0.61) U/L in the STBAS group, and (1. 17 +/- 0.45) U/L in the GHPDS group,
      showing no statistical difference (P > 0.05). There was no statistical difference
      in stereotypic behaviors of rats after treatment among the four different Chinese
      medical syndromes (P > 0.05). At day 7, 14, and 21 after treatment by NDG, the
      times of stereotyped behaviors were significantly less in the XGDS group than in
      the other three groups at the same time points except in the GHPDS group at day
      14 (P < 0.05, P < 0.01). Meanwhile, the total numbers of stereotyped behaviors in
      the XGDS group [(42.8 +/- 12.6)] was obviously superior to that in the GSYDS
      group [(29.3 +/- 13.7)], the STBAS group [(21.9 +/- 10.4)], and the GHPDS group
      [(30.6 +/- 9.6)], showing statistical difference (P < 0.01, P < 0.05) after
      treatment by NDG at day 21. CONCLUSIONS: The anti-neural antibody serum
      concentration in TS children was significantly higher than that in healthy
      children. Stereotyped behaviors could be induced in rats after intrastriatal
      micro-infusion of TS sera rich in anti-neural antibody. TS model rats of XGDS
      were better improved than rats in the other 3 groups after treatment by NDG.

PMID- 24325066
TI  - [Effect of fermented cordyceps powder and prednisone on the Notch2/Hes-1
      signaling activation in the kidney tubules of rats with acute aristolochic acid
      nephropathy].
AB  - OBJECTIVE: To investigate the effect of both fermented Cordyceps powder (CS) and
      prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats
      with acute aristolochic acid nephropathy (AAAN). METHODS: Totally 50 SD rats were
      randomly divided into 4 groups, i.e., the normal group, the model group, the CS
      group, the prednisone group, and the CS plus prednisone group, 10 in each group.
      The AAAN rat model was induced by intragastric administration of pure
      aristolochic acid A at the daily dose of 100 mg/kg for 3 days. Rats in the CS
      group were administered with CS at the daily dose of 5.0 g/kg by gastrogavage,
      while those in the prednisone group were administered with prednisone at the
      daily dose of 0.5 mg/kg. Rats in the CS plus prednisone group were treated by CS
      and prednisone. All treatment lasted for 3 successive weeks. Kidney functions
      [urea nitrogen (BUN) and serum creatinine (SCr)] were detected. The pathological
      changes of kidneys were observed by Hematoxylin-Eosin staining. The apoptosis of
      the renal tubular epithelial cells was detected by TUNEL. The protein expressions
      of Notch2 and Hes-1 in the renal tissue were detected by immunohistochemical
      assay and Western blot. RESULTS: Results of HE staining showed the structure in
      the nephridial tissue was regular in rats of the normal group. The renal tubular
      necrosis occurred in the rats of the model group. The pathological changes of
      kidneys were obviously improved in the CS group, the prednisone group, and the CS
      plus prednisone group. Compared with the normal group, levels of BUN and SCr,
      semi-quantitative score of the tubular interstitial tissue, ratio of apoptotic
      cells, and expressions of Notch2 and Hes-1 proteins significantly increased in
      the model group (P < 0.01). Compared with the model group, the aforesaid indices
      significantly decreased in the 3 treatment groups (P < 0.01). All indices
      decreased most obviously in the CS plus prednisone group (P < 0.05, P < 0. 01).
      CONCLUSIONS: Notch2/hes-1 signaling activation might be associated with apoptosis
      of renal tubular epithelial cells. Both CS and prednisone could play a
      nephroprotective role for AAAN. But CS plus prednisone could achieve the best
      effect. Inhabiting the Notch2/hes-1 signaling activation could be its
      nephroprotective mechanism.

PMID- 24325067
TI  - [Effect and mechanisms of wenyang yiqi huoxue recipe on the apoptosis of
      photoreceptor cells in retinal degeneration slow mice].
AB  - OBJECTIVE: To observe the effect of Wenyang Yiqi Huoxue Recipe (WYHR) on the
      apoptosis of photoreceptor cells in retinal degeneration slow (RDS) mice, and to
      investigate its molecular mechanisms. METHODS: RDS mice were randomly divided
      into the model group and the Chinese medicine group,and C57BL/6J mice were
      selected as the normal control group. Each group consisted of 4 female mice and 2
      male mice. Mice in the Chinese medicine group were administered with WYHR (10
      mg/g) by gastrogavage since mating. Baby mice drunk WYHR decoction instead of
      drinking water once they were born. The offspring were administrated with low
      dose WYHR decoction by gastrogavage from the 7th postnatal day, and the dose was
      increased to that for adult mice from the 21st postnatal day. Physiological
      saline was administrated to mice in the model group and the normal control group
      by gastrogavage. At 18, 28 and 48 postnatal days, electroretinogram (ERG) was
      used to evaluate the retina functional variation, and the apoptotic rate of
      photoreceptor cells was determined by TUNEL staining. HE staining was performed.
      The number of photoreceptor cells of the outer nuclear layer was calculated.
      Furthermore, effect of WYHR on Rhodopsin and basic fibroblast growth factor
      (bFGF) expression was examined using immunochemical assay. RESULTS: Compared with
      the model group, a- and b-wave latency and amplitude, as well as the bFGF
      expression sharply increased in the Max-ERG of the Chinese medicine group (P <
      0.05, P < 0.01) at 18 postnatal days. At 28 and 48 postnatal days, a- and b-wave
      latency and amplitude sharply increased, photoreceptor cell layer numbers of the
      outer nuclear layer obviously increased, the apoptosis rate of retinal
      photoreceptor cells obviously decreased, expressions of Rhodopsin and bFGF in the
      Chinese medicine group significantly increased (P < 0.05, P < 0.01). CONCLUSION:
      WYHR could effectively inhibit the apoptosis of photoreceptor cells in RDS mice,
      which might be attributed to up-regulating bFGF expression.

PMID- 24325068
TI  - [Genomics research on roles of yishen kangxian compound in the TEMT process of HK
      2 cells].
AB  - OBJECTIVE: To study effects of Yishen Kangxian Compound (YKC) and benazepril
      containing serums on HK-2 cells (human renal proximal tubule epithelial cells) in
      the process of renal tubular epithelial cells to mesenchymal myofibroblasts
      transdifferentiation (TEMT) by gene chip. METHODS: YKC and benazepril containing
      serums were prepared. Their inhibitory effects on HK-2 cells in the transforming
      growth factor-beta1 (TGF-beta1)-induced TEMT process were observed. HK-2 cells
      were randomly divided into four groups, i.e., the blank control group, the model
      group, the benazepril group, and the YKC group. The gross RNAs were extracted and
      purified by taking advantage of the HumanHT-12 v4 of IlluminaBeadChip.
      Differentially expressed genes were obtained after they were reversely
      transcribed to cDNA, incorporating biotin labeling probe, hybridized with
      GeneChip, picture signals of fluorescence in gene array scanned and compared with
      differential genes by computer analysis. RESULTS: Differentially expressed genes
      were successfully identified by gene chip. Compared with the model group, there
      were 227 differentially expressed genes in the benazepril group, including 118 up
      regulated genes and 109 downregulated genes. Compared with the model group, there
      were 97 differentially expressed genes in the YKC group, including 69 up
      regulated genes and 28 down-regulated genes. The Gene Ontology (GO) analysis
      indicated that YKC was more actively involved in the regulatory process than
      benazepril in terms of cell damage, apoptosis, growth, NF-KB, protein kinase,
      neuron, and blood vessel growth. CONCLUSIONS: YKC and benazepril could inhibit
      the TEMT process of HK-2 cells. But YKC also had taken part in cell damage,
      apoptosis, growth,and more pathways of early stage TEMT.

PMID- 24325069
TI  - [The ideal of establishing an evaluation system about the combination program of
      Chinese medical pharmacy and western medical pharmacy].
AB  - The necessity of establishing an evaluation system about the combination program
      of Chinese medical pharmacy and Western medical pharmacy was addressed in this
      paper. Besides, its contents were systematically clarified. Besides, existent
      problems and its future development trend were also explained. The author
      believed that it was necessary to perform researches on constructing the
      evaluation system on the basis of patients' needs and physicians'
      responsibilities. The ultimate goal of this system was to produce an optimal
      combination program of Chinese medical pharmacy and Western medical pharmacy for
      a specific disease. This optimal program was the results of comparing and
      analyzing the therapeutic efficacies of different combination programs. In this
      program, Chinese medical pharmacy and Western medical pharmacy combined together.
      On the one hand, it is safe; on the other hand, they do not produce adverse
      reaction. Their therapeutic effects were synergetic. Chinese medical pharmacy
      could not only advance the cure effects of Western medical pharmacy, but also
      supplement the insufficiency of Western medical pharmacy. Of course, the author
      put forward some assumptions only from the perspective of clinical application in
      this paper. The evaluation system will become perfect along with further
      deepening researches of basic sciences.

PMID- 24325070
TI  - [Application of Chinese medicine in assisted reproductive techniques].

PMID- 24325071
TI  - [Progress of pharmacological actions of total glucosides of paeony in treating
      diabetic nephropathy].

PMID- 24325073
TI  - Human inertia.

PMID- 24325072
TI  - [Progress of Chinese medicine on post-operative gastrointestinal functions].

PMID- 24325074
TI  - Why would someone refuse the best choice of treatment?
AB  - This brief overview reports the findings of the most relevant studies regarding
      the risk factors for refusing implants and recommendations to reduce treatment
      refusal.

PMID- 24325075
TI  - Oral cancer screening day at the State House in Trenton.

PMID- 24325076
TI  - Oral pathology quiz #80. Case number 1. Mucous membrane pemphigoid.

PMID- 24325077
TI  - Oral pathology quiz #80. Case number 2. Peripheral giant cell lesion (incipient).

PMID- 24325078
TI  - Oral pathology quiz #80. Case number 3. Odontogenic keratocyst.

PMID- 24325079
TI  - Oral pathology quiz #80. Case number 4. Dentigerous cyst.

PMID- 24325080
TI  - How to turn patients into raving fans.

PMID- 24325081
TI  - Implant-supported overdentures.
AB  - Retention of the lower complete denture is always a question for the dentist and
      the patient because of the alveolar ridge resorption and many muscle attachments
      to the mandible. The treatment of edentulous patients using oral implants does
      not always permit the placement of an adequate number of implants for fixed
      prosthesis construction; the reasons are insufficient anatomical bone height of
      the alveolar ridge, health restrictions and financial limitations. Placement of
      two dental implants in the cuspid regions anterior to the mental foramina on
      either side will improve the retention and stability of complete dentures in
      edentulous patients. Implant-supported overdentures with ball and socket
      attachments are more successful, provide good retention, stability for the
      denture and improve comfort and confidence for the edentulous patient while
      speaking and masticating.

PMID- 24325082
TI  - Magnesium: its role in nutrition and carcinogenesis.
AB  - Magnesium (Mg2+) plays a key role in many essential cellular processes such as
      intermediary metabolism, DNA replication and repair, transporting potassium and
      calcium ions, cell proliferation together with signalling transduction. Dietary
      sources rich in magnesium are whole and unrefined grains, seeds, cocoa, nuts,
      almonds and green leafy vegetables. Hard water is also considered to be an
      important source of magnesium beneficial to human health. The daily dietary
      intake of magnesium is however frequently found to be below that recommended in
      Western countries. Indeed, it is recognised that magnesium deficiency may lead to
      many disorders of the human body, where for instance magnesium depletion is
      believed to play an important role in the aetiology of the following;
      cardiovascular disease (including thrombosis, atherosclerosis, ishaemic heart
      disease, myocardial infarction, hypertension, arrhythmias and congestive heart
      failure in human), as well as diabetes mellitus, gastrointestinal (GI) tract
      disease, liver cirrhosis and diseases of the thyroid and parathyroid glands.
      Insufficient dietary intake of magnesium may also significantly affect the
      development and exacerbation ofADHD (Attention Deficit- Hyperactivity Disorder)
      symptoms in children. The known links between magnesium and carcinogenesis still
      remain unclear and complex, with conflicting results being reported from many
      experimental, epidemiological and clinical studies; further knowledge is thus
      required. Mg2+ ions are enzyme cofactors involved in DNA repair mechanisms that
      maintain genomic stability and fidelity. Any magnesium deficiencies could thereby
      cause a dysfunction of these systems to occur leading to DNA mutations. Magnesium
      deficiency may also be associated with inflammation and increased levels of free
      radicals where both inflammatory mediators and free radicals so arising could
      cause oxidative DNA damage and therefore tumour formation. The presented review
      article now provides a summary discussion of the various research performed
      concerning the impact that low magnesium intake has on tumour incidence; this
      includes impairment of magnesium homeostasis frequently observed in tumour cells,
      the influence of magnesium depletion on the progression of existing tumours and
      the occurrence of hypo-magnesaemia when patients are treated with certain
      anticancer drugs.

PMID- 24325083
TI  - Studies of acrylamide level in coffee and coffee substitutes: influence of raw
      material and manufacturing conditions.
AB  - BACKGROUND: Many animal studies have shown that acrylamide is both neurotoxic and
      carcinogenic. The first reports of acrylamide actually having been found in
      foodstuffs were published in 2002 by the Swedish National Food Agency in
      conjunction with scientists from the University of Stockholm. It has since been
      demonstrated that acrylamide arises in foodstuffs by the Maillard reaction, ie.
      between free asparagine and reducing sugars at temperatures >120 degrees C.
      Coffee in fact, forms one of the principal dietary sources of acrylamide, where
      it is normally drunk in large quantities throughout many countries worldwide that
      includes Poland. Thus, it constitutes a major dietary component in a wide range
      of population groups, mainly ranging from late adolescents to the elderly.
      OBJECTIVES: To determine the acrylamide level in commercial samples of roasted
      and instant coffee and in coffee substitutes by LC-MS/MS method. The influence of
      coffee species and colour intensity of coffee on acrylamide level was also
      detailed. MATERIALS AND METHODS: A total of 42 samples of coffee were analysed
      which included 28 that were ground roasted coffee, 11 instant coffees and 3
      coffee substitutes (grain coffee). Analytical separation of acrylamide from
      coffee was performed by liquid chromatography followed by tandem mass
      spectrometry (LC-MS/MS). To evaluate the colour intensity of ground roasted
      coffee and instant coffee we used method of arranging (sequence). RESULTS: The
      highest mean acrylamide concentrations were found in coffee substitutes (818
      pg/kg) followed by instant coffee (358 microg/kg) and then roasted coffee (179
      microg/kg). One single cup of coffee (160 ml) delivered on average from 0.45
      microg acrylamide in roasted coffee to 3.21 microg in coffee substitutes. There
      were no significant differences in acrylamide level between the coffee species
      ie. Arabica vs Robusta or a mixture thereof. The various methods of coffee
      manufacture also showed no differences in acrylamide (ie. freeze-dried coffee vs
      agglomerated coffee). A significant negative correlation was observed between
      acrylamide levels and the intensity of colour in roasted coffee; this was not the
      case however for instant coffee. CONCLUSIONS: It was demonstrated that roasting
      process had the most significant effect on acrylamide levels in natural coffee,
      however there were no relationships found with coffee species. Due to the high
      acrylamide levels demonstrated in coffee substitutes, recommended amounts should
      be defined and manufacturers should be obliged to reduce such levels in these
      products.

PMID- 24325084
TI  - Evaluation of fatty acids daily intake and diets atherogenicity of dietetics
      students of Wroclaw Medical University.
AB  - BACKGROUND: Dietary and lifestyle risk factors play an important role in the
      pathogenesis of cardiovascular disease (CVD). The excessive intake of products
      that could affect atherogenic effect and are rich sources of saturated fatty
      acids (SFA) and cholesterol conductive the occurrence of lipid metabolism
      disturbances in the body. OBJECTIVE: Evaluation of fatty acids dietary intake and
      assessment of the students' diets atherogenicity in the aspect of the CVD risk.
      MATERIAL AND METHODS: The study was conducted in 2011-2012. The study group
      included 100 females, dietetic students of the Wroclaw Medical University. The
      average age of the students was 21 years. Dietary habits were evaluated by the 3
      day diet record method including one weekend day. RESULTS: Average energy intake
      was 1673.9 kcal per day. The average daily total fat intake was 65.4 g and
      provided 34.5% of total energy intake. The percentage of energy from SFA in the
      diets of 82% students exceeded the recommended 10% and averaged 13.1%. The
      average percentage of energy from monounsaturated fatty acids (MUFA) in the
      students diets was 12.9% and in the diets of 5% students did not exceeded
      recommended 10%. The average percentage of energy from polyunsaturated fatty
      acids (PUFA) was 5.7% and in the diets of 66% students did not fulfilled the
      recommended 6-10%. About 80% of the students consumed less than recommended 2 g
      of C 18:3 per day. Insufficient intake of EPA and DHA was observed in 71%
      students' diets. The average n-6/n-3 PUFA ratio was 7.2 and in the 76% of female
      diets exceeded the recommended value of 4:1. The diets of 80% of students were
      considered as atherogenic, because of elevated value of Keys score. The ratio
      between PUFA and SFA in the female diets was incorrect and amounted to 0.52
      (recommended value > 1.0). CONCLUSIONS: Incorrect energy intake from daily diet
      and improper dietary intake of selected fatty acids in the diets of students may
      contribute to the development of CVD.

PMID- 24325085
TI  - Studies to determine nutrition behaviour amongst middle school pupils living in
      the border areas of Poland and the Czech Republic.
AB  - BACKGROUND: In childhood and adolescence, adequate nutrition is vital for
      ensuring correct physical, mental and emotional development as well as effective
      learning ability. Thus, the acquiring of such healthy lifestyle behaviour is also
      important later in adult health. OBJECTIVES: To assess and compare the dietary
      habits of pupils attending middle school in Poland and the Czech Republic, who
      live in the border regions between these countries. MATERIAL AND METHODS: The
      study tool was a nutrition questionnaire dived into a section on socio-economic
      status and one on detailed dietary habits. Subjects were 202 pupils recruited
      from Poland and 202 from the Czech Republic. Statistical analyses were performed
      by the Statistica Ver. 9.0 software, where the Chi2 test was used to evaluate the
      significance of differences between the data, taking p <or= 0.5 as the critical
      value. RESULTS: There were 47% of pupils eating 4-5 meals daily and 49% and 50%
      ate breakfast and lunch respectively. Milk or dairy drinks were daily drunk by
      24% pupils daily and 14% ate hard or processed cheese. Fish was consumed 1-2
      times weekly by 46% subjects and fruit and vegetables were daily eaten by 49% and
      36% of pupils respectively. CONCLUSIONS: Pupil's dietary habits were found to be
      unfavourable in both countries. There were significant differences between the
      countries tested, especially in how frequently breakfast and lunch were eaten, as
      well as in the intakes of milk and dairy products and in the consumption of fast
      food and sugary drinks.

PMID- 24325086
TI  - The risk of overweight and obesity in chronic diseases among Warsaw inhabitants
      measured by self-reported method.
AB  - BACKGROUND: Obesity is well known cause of various diseases. However, there are
      only a few studies which enable to compare directly the magnitude of risk in
      different groups of chronic diseases. OBJECTIVES: The aim of presented paper was
      to identify a magnitude of the risk of chronic diseases attributable to
      overweight and obesity on the basis of data on weight and height self-reported by
      respondents. MATERIAL AND METHODS: The survey was conducted among 402 Warsaw
      inhabitants selected by non-random method. Overweight and obesity was measured by
      Body Mass Index (BMI) on the basis of the data of weight and height reported by
      respondents. According to WHO criteria the normal weight is defined as BMI 18.5 -
      24.9 kg/m2, overweight as BMI 25.0 - 29.9 kg/m2, and obesity as BMI 30 kg/m2 or
      more. The following groups of chronic diseases were included: cancer, diabetes
      and other endocrine diseases, mental disorders, cardiovascular diseases,
      respiratory diseases, digestive diseases, arthritis and allergy disorder.
      RESULTS: Obesity measured by self-reported method was recognised as significant
      risk factor for diabetes (OR=9.6, CI: 2.0-152.8), respiratory diseases (OR=10.6,
      CI: 3,0-333,7), cardiovascular diseases (OR=5.2, CI: 1.9-108.3), arthritis
      (OR=6.3, CI: 2.4-266.7), digestive diseases (OR=3,8, CI: 1.3-83.6) and mental
      disorders (OR=5.8, CI: 1.5-29.1), while overweight significantly increased the
      risk of diabetes (OR=4.4, CI: 1.2-10.8), respiratory diseases (OR=3.2, CI: 1.4
      22.2), cardiovascular diseases (OR=2.9, CI: 1.2-6.4) and arthritis (OR=3.0, CI:
      1.1-9.6) CONCLUSIONS: Our findings showed that data on weight and height
      collected by survey method provide some information about the magnitude of the
      risk regarding particular groups of diseases attributable to overweight and
      obesity, nevertheless, underestimation of BMI calculated in this way should be
      taken into account.

PMID- 24325087
TI  - Trends of premature mortality in Swietokrzyskie Province (Poland), years 2002
      2010.
AB  - BACKGROUND: Premature mortality in younger age groups influences the society as
      far as social and economic aspects are concerned. Therefore, it is important to
      come up with a tool which will allow to assess them, and will enable to implement
      only these health care measures that bring tangible benefits. That is the reason
      for introducing PYLL rate (PYLL - potential years of life lost), which is an
      addition to the analysis of premature mortality as it includes the number of
      deaths due to a particular cause and the age at death. OBJECTIVE: The purpose of
      this study was to analyse the level and trends of PYLL rate according to death
      causes in years 2002 -2010 in Swietokrzyskie Province. MATERIAL AND METHODS: The
      material for the analysis was the information from the Central Statistical Office
      on the number of deaths due to all causes registered among the inhabitants of
      Swiytokrzyskie Province in years 2002-2010. Causes of death were coded according
      to the 10th revision of the International Classification of Diseases. The
      analysis of premature mortality was carried out with the use of PYLL rate. PYLL
      rate was calculated according to the method proposed by Romeder, according to
      which the premature mortality was defined as death before the age of 70. The
      analysis of time trends of PYLL rate and the APC (annual percent change) of the
      PYLL rate were calculated using jointpoint model as well as the Jointpoint
      Regression Program (Version 4.0.1 - January 2013). RESULTS: In men, in years 2002
      - 2007 PYLL rate increased by 1.5% per year (p<0.05). From year 2007 the trend
      went downward and PYLL rate decreased on average by 3.1% per year till year 2010.
      External causes of death, cardiovascular diseases and cancers in years 2002 -
      2010 were the reason for almost 74.0% PYLL in men. In year 2010 PYLL rate due to
      all death causes amounted to 8913.8/105 and was three times higher than in women
      (2975.5/10(5)). In women, however, during the analysed period PYLL rate did not
      change significantly, and was dominated by cancers, cardiovascular diseases and
      external death causes. Similarly to men, those three groups of death causes were
      responsible for an average 76.0% PYLL. CONCLUSIONS: The analysis of the causes of
      premature mortality in Swietokrzyskie Province shows that in the majority of
      cases it is due to preventable deaths, which calls for the necessity of more
      intensive measures in primary and secondary prevention as well as the improvement
      in treatment standards, mainly of cardiovascular diseases, cancers, injuries and
      accidents.

PMID- 24325088
TI  - Nutritional assessment in Polish men with cardiovascular diseases.
AB  - BACKGROUND: Cardiovascular disease is the most common cause of death in Poland,
      where many factors have been found responsible such as obesity, smoking
      cigarettes and a lack of physical activity. Amongst these are also nutritional
      determinants, which principally include the amount and types of dietary fatty
      acids consumed, coupled with low intakes of antioxidant-rich fruit and
      vegetables. OBJECTIVES: To assess nutrition in male subjects suffering from
      cardiovascular disease. MATERIALS AND METHODS: Subjects were 95 men with
      cardiovascular disease aged 30-90 years. Nutrition was assessed by weighed food
      records over 3 days. The calorific dietary intake, as well as the proportions of
      calories derived from dietary protein, carbohydrates and fat were also
      calculated; this included vitamins and minerals. RESULTS: Only 18% subjects had a
      normal Body Mass Index (BMI); the rest falling into the overweight or obesity
      ranges. The average dietary calorific daily intakes were abnormally low at 1582
      kcal/person, however the proportions of fat and protein making up this value were
      too high; respectively at 36% and 19%. The average daily consumption per person
      of cholesterol, fibre and vegetables were respectively 251 mg, 19 g and 608 g. A
      significant number were deficient in dietary minerals (eg. calcium, potassium and
      magnesium) as well as vitamins; especially A, B, and B2. CONCLUSIONS: Persons
      suffering from cardiovascular disease require a diet with sufficient calories for
      their body needs. It is also vital that the dietary sources of energy are
      properly balanced between protein, carbohydrates and fats as well as having
      appropriate intakes of both vitamins and minerals (eg. calcium, magnesium and
      potassium).

PMID- 24325089
TI  - Assessment of the quality of diet of Alzheimer's disease individuals living at
      homes and in nursing homes.
AB  - BACKGROUND: In case of many individuals, decrease of body mass is observed during
      aging, that is often in elderly living in nursing homes. It is especially
      important for patients with Alzheimer's disease (AD), when decrease of body mass,
      resulting in malnutrition. OBJECTIVE: The aim of the study was the assessment of
      the quality of diet of AD individuals living at homes and in nursing homes, in
      comparison with a control group MATERIAL AND METHODS: In the study participated
      160 individuals with and without AD, living at home or in nursing homes.
      Assessment of diet of individuals living at homes was based on self-reported data
      from one-day dietary recall. Assessment of diet of individuals living in nursing
      homes was based on one-day menu from nursing homes accompanied by information
      about snacking between meals. The diets were assessed on the basis of qualitative
      meal classification method of Bieliiska and Kulesza. RESULTS: Individuals living
      in nursing homes consumed meals more often than living at homes, while AD did not
      have any impact on it. Individuals consuming fruits and vegetables not often
      enough were in all the groups, however, in case of individuals living at homes it
      was serious problem. Consuming animal products to almost all main meals was
      observed in case of many individuals in all analyzed groups. Composition of
      majority of main meals and small amount of lunches and afternoon snacks was
      rational. CONCLUSIONS: Improperly balanced diet following observed not only in a
      group of AD individuals but also of ones without dementia (both living at homes
      and in nursing homes), may result in dietary deficiencies.

PMID- 24325090
TI  - Nutritional assessment of selected patients with cancer.
AB  - BACKGROUND: It is recognised that both nutritional status and an improper diet
      have significant effects on weakening the outcomes of treatment in cancer
      patients. As a result, a lowered response to therapy and an increase in untoward
      side effects is often observed leading to a deteriorating quality of life. The
      role of an adequately balanced diet is thus regarded as being vital in supporting
      recovery. OBJECTIVE: To assess the dietary consumption of calories, macro
      elements and selected vitamins and minerals for subjects diagnosed with cancers
      of the breast, lungs and bones or soft tissue. MATERIAL AND METHODS: A survey was
      performed on 100 subjects diagnosed with various tumours between the September
      and December months of 2011 consisting of 34 with breast cancer, 33 lung cancer
      and 33 with bone or soft tissue cancer. The questionnaire was devised in-house,
      which included a three day dietary record. Results. The average daily calorific
      intake was found to be inadequate at 1608 kcal. In addition, abnormal proportions
      of energy derived from macro-elements was seen, where the contributions made by
      fats and proteins were somewhat high at respectively 35.1% and 16.5%, but too low
      in the case of carbohydrates at 52.1%. Up to 78% subjects had insufficient
      protein intakes, 88% showed deficiencies in consuming carbohydrates, as were 89%
      for fibre, 85% vitamin C, 99% calcium, 98% magnesium and 81% for iron.
      CONCLUSIONS: Many dietary shortcomings were observed in the studied subjects.
      There is therefore a need to educate persons suffering from cancer to adopt an
      adequate and balanced diet as means of providing vital support for treatment to
      be more effective.

PMID- 24325091
TI  - Activity of alpha-fucosidase and beta-glucuronidase in serum and urine of
      patients administered parenteral nutrition.
AB  - BACKGROUND: In hospital patients suffering from adverse clinical and biochemical
      symptoms of malnutrition, it is often necessary to employ parenteral nutrition to
      avoid the body's tissue becoming broken down by being metabolised. Thus, the
      patient's welfare and survival can be supported throughout any periods of medical
      crisis. Two of the enzymes responsible for metabolising glycoconjugates are alpha
      fucosidase (FUC) and beta-glucuronidase (GLU), present in lysosomes. They release
      fucose or glucuronic acid from the non-reducing end of oligosaccharide chains.
      OBJECTIVE: To determine the effect of parenteral nutrition administered to ill
      patients, on glycoconjugate metabolism, by measuring serum and urinary activities
      of FUC and GLU. Material and methods. Blood samples and the daily urine
      collection were taken from 23 patients' who had been undergoing parenteral
      nutrition for either 5 or 10 days, as well as from a baseline sample. Enzyme
      activities in serum and urine were determined by the method of Zwierz et al.
      RESULTS: Serum FUC activities were significantly lower after 10 days compared to
      5, (p< 0.0172), whereas GLU activities were significantly lower after both 5 and
      10 days, (p< 0.0007 and p< 0.0208 respectively), compared to levels before
      starting parenteral nutrition. GLU activities were however higher after 10 days
      than those after 5 days, (p< 0.0023). In urine, FUC activities were significantly
      decreased after 10 days compared to 5 days after starting parenteral nutrition,
      (p< 0.0245). Urine GLU activities were unaffected by parenteral nutrition nor was
      any effect seen on FUC or GLU activities when calculated per 1mg creatinine.
      CONCLUSIONS: Serum FUC and GLU activities can be used for assessing the effect of
      parenteral nutrition on glycoconjugate metabolism. The significant decreases of
      serum GLU activity observed after 5 and 10 days, may serve to indicate that the
      components of parental nutrition are appropriate and that the body has become
      suitably adapted to this form of nutrition.

PMID- 24325092
TI  - Determining the current status and potential of nuclear medicine in Poland.
AB  - BACKGROUND: Through its use of ionising radiation, the field of nuclear medicine
      forms a unique and significant part of medical diagnostics and patient treatment.
      Objectives. To assess the operational potential of nuclear medicine in Poland
      based on existing database/literature sources together with conducting a survey
      on the relevant healthcare facilities available, staffing, expertise and
      performance. MATERIAL AND METHODS: To gather all available literature data on the
      medical use of ionising radiation in Poland several data bases were used, since
      currently, there are no single statistical data base devoted to this issue. Data
      on radiation hygiene were thus collected from the Statistical Bulletin of the
      Ministry of Health, Annual reports from the National Atomic Energy Agency and
      Central Statistics Office. Additionally, national and provincial reports were
      used, as well as those received from the European Society of Nuclear Medicine.
      RESULTS: At present, the Public Healthcare system in Poland has 55 nuclear
      medicine departmental facilities operating and 8 that are private/non-public.
      These are staffed by 252 doctors, of whom 151 are qualified as nuclear medicine
      specialists; constituting one specialist per 300,000 inhabitants. In addition,
      170 highly qualified staff (biologists, chemists, physicists, electronics
      engineers and IT specialists) provide indispensable scientific/operational
      support and are vital for the development of nuclear medicine departments. They
      are mainly responsible for ensuring that all equipment functions effectively and
      for developing new diagnostic techniques, together with new radiopharmaceuticals.
      Furthermore, there are approximately 500 other staff at intermediate-level also
      involved in nuclear medicine departments, such as technicians, nurses and support
      workers. The survey demonstrated an average of 22 persons employed per nuclear
      medicine department. For all institutions, it is estimated that there are 127
      gamma cameras, 10 PET/CT scanners and 16 hybrid SPECT/CT systems operating. In
      2000, approximately 117,435 diagnostic procedures were performed, compared to
      156,214 in 2008 and with the current number of around 170,000; up to 38% were
      simple thyroid scintigraphies, 25% were bone scans, 11% heart scintigraphies and
      10% kidney scans. CONCLUSIONS: The number of diagnostic radioisotopic procedures
      in Poland are strongly expected to increase by 300% during the next 5-6 years. To
      meet this rise, additional equipment will thus be necessary, which includes
      having an extra 100 SPECT/CT gamma cameras.

PMID- 24325093
TI  - [Suppressive effects of gamma-secretase inhibitor DAPT on the proliferation of
      pancreatic cancer cells].
AB  - OBJECTIVE: To explore the effect of DAPT, a gamma-secretase inhibitor on the
      proliferation of pancreatic cancer cells and its underlying mechanism. METHODS:
      Three human pancreatic cancer cell lines as AsPC-1, BxPC-3 and MIAPaCa-2 were
      employed for in vitro experiments. Cell proliferation was tested by CCK-8 and
      cell apoptosis was examined by Annexin V/PI staining after the treatment of
      various concentrations of DAPT at different time. RESULTS: DAPT of 100 micromol/L
      significantly inhibited the proliferation of these 3 cell lines from day 3 to 5.
      DAPT of 50 micromol/L inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells
      from day 3 to 5, whereas the effect of inhibition was only observed at day 5 in
      AsPC-I cell. DAPT of 10 micromol/L inhibited the proliferation of BxPC-3 and
      MIAPaCa-2 cells at day 5, whereas no effect was found in AsPC-1. Flow cytometry
      test showed that cell apoptosis rate was higher in DAPT treatment groups compared
      with control group. CONCLUSION: DAPT could suppress the proliferation of
      pancreatic cancer cell, with the mechanism of promoting cell apoptosis.

PMID- 24325094
TI  - [Effect of PML(NLS-) gene mediated by recobinant adenovirus vector on emodin
      induced apoptosis of HL-60 cells].
AB  - OBJECTIVE: To determine the effect and mechanism of action of PML(NLS-) gene on
      emodin-induced apoptosis of human HL-60 cells. METHODS: HL-60 cells were infected
      with recombinant adenovirus Ad-PML (NLS-) and Ad-KZ, respectively. The PML(NLS-)
      gene was detected by Real-time PCR(RT-PCR) and Western blot. The proliferation
      level of the HL-60 cells was determined by MTT method. The HL-60 cells were
      treated with 60 micromol/L emodin for 72 h and then analyzed by flow cytometry
      for their cell cycle and apoptosis rate. The transcription levels of apoptosis
      related BCL-2, BAX and C-MYC genes were determined by RT-PCR. The translation
      levels of those genes were determined by Western blot. RESULTS: Compared with
      normal controls and the HL-60 cells infected with Ad-KZ, the mRNA and protein
      expression levels of PML(NLS-) gene increased significantly in the HL-60 cells
      infected with Ad-PML( NLS-). Increased proliferation levels of the Ad-PML (NLS-)
      infected HL-60 cells were observed in those treated with 60 pmol/L emodin, which
      showed decreased percentage of cells at Gx phase, increased percentage of cells
      at S phase, and decreased emodin-induced apoptosis. The levels of mRNA
      transcription and protein expression of BAX gene decreased, while those of BCL-2
      and C-MYC genes increased significantly. CONCLUSION: The over-expression of
      PML(NLS-) gene might promote the proliferation and arrest the apoptosis of HL-60
      cells by up-regulating the expressions of BCL-2 and C-MYC genes and down
      regulating the expression of BAX gene.

PMID- 24325095
TI  - [Optimal time for MRI scanning of tumors in BALB/c mice using c-erbB2 antisense
      probe labeled with superparamagnetic iron oxide nanoparticles].
AB  - OBJECTIVE: To determine the optimal time for MRI scanning of tumors in BALB/c
      mice using c-erbB2 antisense probe labeled with superparamagnetic iron oxide
      nanoparticles. METHODS: SK-Br-3 tumor-bearing BALB/c mice (n= 30) were injected
      with antisense probe (12.0 mg Fe/kg). MRI scanning was performed on 5 mice before
      the injection and 60 min, 180 min, 360 min, 720 min and 1 440 min after the
      injection, respectively. Tumor tissues were taken immediately after the scanning
      and fixed with 10% formalin and paraffin-embedded sections. The MRI signal
      strength of the tumors and adjacent muscles were compared with changes detected
      under a microscope using HE and Prussian blue staining. RESULTS: SK-Br-3 tumors
      were introduced to the BALB/c mice successfully. The strongest signal intensity
      was detected by the MRI 360 min after injection with the antisense probe. The
      pathological examination revealed structural disorders of the tumor issues, with
      a large number of special-shaped cells arranged in a cancer nest shape. Punctuate
      blue iron particles were observed in all of the tumor issues, with the greatest
      density occurring at 360 min after the injection with the antisense probe.
      CONCLUSION: The MR4 optimal time for MRI scanning of tumors in BALB/c mice using
      c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles
      should be set at 360 min after injection.

PMID- 24325096
TI  - [Apoptosis of A549 cells induced by cloned Noxa gene].
AB  - OBJECTIVE: To clone the Noxa gene and to observe the apoptosis of A549 cells
      transfected with the recombinant plasmid of pcDNA-Noxa. METHODS: The Noxa gene
      was obtained by PCR, and was cloned into pcDNA3. 1(-). A549 cells were
      transfected with the recombinant plasmid of pcDNA-Noxa. Western blot analysis was
      performed to determine the overexpression of Noxa. A549 cells were stained with
      Hoechst 33258 to observe the apoptosis. RESULTS: The recombinant plasmid of pcDNA
      Noxa was successfully constructed evidenced by endonuclease digestion and
      sequence analysis. The overexpression of Noxa was identified using Western blot
      analysis. The recombinant plasmid of pcDNA-Noxa induced apoptosis of A549 cells.
      CONCLUSION: Nora has exhibited potential pro-apoptotic activity against A549
      cells. This study is a foundation for further research into pro-apoptotic
      activity of Noxa gene.

PMID- 24325097
TI  - [Oxidative mechanism of uric acid induced CRP expression in human umbilical vein
      endothelial cells].
AB  - OBJECTIVE: To explore the oxidative mechanism of uric acid (UA) induced CRP
      expression in human umbilical vein endothelial cells. METHODS: Different
      concentrations of UA (0 mg/dL, 4 mg/dL, 8 mg/dL, 12 mg/dL, 16 mg/dl) were
      incubated 12 h with HUVECs, and HUVECs were stimulated with 12 mg/dl. UA for
      different times (6 h, 12 h, 24 h, 48 h). CRP mRNA and protein expression were
      determined by real-time quantitative polymerase chain reaction (RT-qPCR) and
      Western blot, respectively; the effects of uric acid on the intracellular
      reactive oxygen species (ROS) production in HUVECs were measured by fluorescence
      microscope and flow cytometric analysis using a 2', 7'-Dichlorofluorescin
      diacetate (DCF-DA) fluorescence probe. The effects of N-acetyl cysteine (NAC) on
      UA-induced levels of ROS, mRNA and protein of CRP in HUVECs were also observed.
      RESULTS: The results demonstrated that UA could significantly increase the mRNA
      and protein expression of CRP in HUVECs in time- and concentration-dependent
      manners. HUVECs were stimulated with 12 mg/dL UA at 6 h, mRNA and protein levels
      of CRP significantly higher than that of control level (P<0.05), reached a peak
      at 12 h (P<0. 01). NAC reduced UA-induced levels of ROS, mRNA and protein of CRP
      in HUVECs compared with those of 12 mg/dL UA induced group(P<0. 05). CONCLUSION:
      Uric acid significantly increased mRNA and protein expression of CRP in HUVECs in
      time- and concentration-dependent manners. Its mechanism may be associated with
      uric acid induced increasing of ROS levels in endothelial cells, which suggested
      that the uric acid mediated oxidative stress and inflammation may be involved in
      the injury of endothelial cells.

PMID- 24325098
TI  - [The role of NMDA and NK1 receptors in cardiac nociceptive information
      transmissions in the spinal cords of rats].
AB  - OBJECTIVE: To determine the effects of NMDA and NK1 receptor agonist and
      antagonist on the EMG and the synaptic mechanism of nociceptive information
      transmissions in the spinal cords. METHODS: Male SD rats were randomly divided
      into seven groups, with intrathecal injection of the following chemicals
      respectively: control group (10 microL saline), NMDA group (0.147 microg/10 pL
      NMDA), MK801 group (6.8 microg/10 microL MK801), MK801+NMDA group (6.8 microg/10
      pL MK801+0. 147 microg/10 pL NMDA), Sar-SP group (1.4 pg/10 microL Sar-SP), CP
      96345 group (5 microg/10 pL CP-96345), and CP-96345+Sar-SP group (1.4 micro/10
      microL Sar-SP+5 microg/10 microL CP-96345). A cardiac pain model in rats through
      intrapericardial injection of capsaicin was established. Intrapericardial
      injection of capsaicin was given to the rats 10 min after intrathecal injection
      of the tested chemicals. The spinotrapezius electromyography (EMG) activities as
      an index of cardiac-somatic motor reflex were recorded simultaneously. RESULTS:
      Compared with the pre-test controls (100%), saline did not make a significant
      change to the capsaicin-evoked EMG response (96. 9% +/- 12. 5%, P>0. 05); NMDA
      agonist increased the capsaicin-evoked EMG response (185. 2% +/- 24. 4%)
      significantly (P<0. 05); neither MK801 nor a combined administration of MK801 and
      NMDA made a significant change to the capsaicin-evoked EMG response (106. 6% +/-
      10. 2%, P> 0.05); Sar-SP increased the capsaicin-evoked EMG response (145. 6% 10.
      1%) significantly (P<0. 05); whereas neither CP-96345 nor a combined
      administration of CP-96345 and Sar-SP made a significant change to the capsaicin
      evoked EMG response (102. 2% +/- 8. 4%, P>0.05). CONCLUSION: NMDA and NK1
      receptors may have participated in the transmissions of cardiac nociception
      information in the spinal cords of rats.

PMID- 24325099
TI  - [The association study of the LIPC -250g/A polymorphism and high-carbohydrate/low
      fat diet induced serum lipid and apolipoprotein concentration changes in healthy
      youth].
AB  - OBJECTIVE: To investigate the role of the - 250G/A polymorphism in the promoter
      region of hepatic lipase gene (LIPC) on serum lipid profile and its interactions
      with a high-carbohydrate/low-fat (HC/LF) diet on serum lipid profiles in a young
      healthy Chinese population. METHODS: After a stabilization diet for seven days,
      fifty-six young healthy subjects (27 males, 29 females) were given the HC/LF diet
      for six days. The serum lipid profiles were analyzed of the twelve-hour fasting
      venous blood samples collected in the mornings of the first, the eighth and the
      fourteenth days. The concentrations of serum apolipoproteins were measured. The
      LIPC -250G/A polymorphism were analyzed. RESULTS: At baseline, the female
      subjects with the GG genotype had significantly higher high-density lipoprotein
      cholesterol (HDL-C) (P= 0. 041) and apolipoprotein A- I (Apo A- I ) (P= 0. 020)
      than the male subjects with the same genotype. After the stabilization diet, the
      females had significantly higher HDL-C (GG genotype: P=0. 021, A carriers: P=0.
      014) and Apo A-I (GG genotype: P= 0. 035, A carriers: P= 0. 006) than the males
      in all genotypes. After the HC/LF diet, the female A carriers had significantly
      higher total cholesterol (TC) (P= 0. 042) than the male A carriers, and the
      females had significantly higher Apo A- I than the males in all genotypes (GG
      genotype: P=0. 010, A carriers: P=0. 009). Compared with thosebefore the HC / LF
      diet , TC ( males with GG genotype : P = 0. 013 , male A carriers: P = 0. 000 ;
      females with GG genotype: P=0. 025, female A carriers: P=0. 048) and low-density
      lipoprotein cholesterol (LDL-C) (males with GG genotype: P = 0. 028, male A
      carriers: P = 0. 000; females with GG genotype: P= 0. 004, female A carriers:
      P=0. 001) significantly decreased after the diet in all the subjects.
      Triglycerides (TAG) (GG genotype: P=0. 006, A carriers: P= 0. 001) significantly
      increased in the females regardless of the genotype. However, only in the male A
      carriers, HDL-C (P= 0. 011) and Apo A- I (P= 0. 041) significantly increased
      after the diet. CONCLUSION: The A allele at the LIPC -250G/A polymorphism is
      associated with the HC/LF diet induced HDL-C and Apo A-I concentration changes in
      the males.

PMID- 24325101
TI  - [Expression of DUOX2 in psoriasis and atopic dermatitis lesion].
AB  - OBJECTIVE: To investigate the expression of dual oxidase 2 (DUOX2) in psoriasis
      vulgaris lesions, atopic dermatitis (AD) lesions and normal skin and its role in
      cutaneous anti-inflammation. METHODS: Tissue samples were harvested from
      psoriasis lesion area, psoriasis non-lesion area, AD lesion area and AD non
      lesion area, as well as normal skin, the expression level of DUOX2 protein was
      detected by immunohistochemical staining. The mRNA level of DUOX2 was detected by
      reverse transcription polymerase chain reaction (RT-PCR) analysis. RESULTS: The
      expression of DUOX2 protein was observed in all groups which mainly located in
      basal layer, spinous layer and dermal papilla layer. Compared with the psoriasis
      non-lesion group and normal skin group, the expression level of DUOX2 protein in
      psoriasis lesion group was significant higher (P<0. 01). The expression of DUOX2
      protein in AD lesion group was stronger than that in AD non-lesion group and
      normal skin group (P<0. 01). In addition, the expression level of DUOX2 protein
      in AD lesion group was significant higher than that in psoriasis lesion group
      (P<0. 01). RT-PCR test revealed DUOX2 mRNA was expressed positively in psoriasis
      and AD lesions. CONCLUSION: The strong expression of DUOX2 in psoriasis vulgaris
      lesion and AD lesion suggested that DUOX2 may play an important role in the
      mechanisms of cutaneous anti-inflammation.

PMID- 24325100
TI  - [Effects of an insertion/deletion polymorphism of angiotensin converting enzyme
      gene on the changes of serum lipid ratios and blood pressure induced by a high
      carbohydrate and low-fat diet].
AB  - OBJECTIVE: To investigate the effects of an insertion/deletion (I/D) polymorphism
      at the intron 16 of the gene of angiotensin converting enzyme (ACE) on the
      changes of serum lipid ratios and blood pressure induced by a high-carbohydrate
      and low-fat (HC/LF) diet in healthy Chinese Han youth. METHODS: Fifty six healthy
      Chinese Han young volunteers were enrolled. A washout diet was given for seven
      days followed by the HC/LF diet for six days. Serum lipids and blood pressure
      were measured on the 1st, 8th, and 14th days. Serum lipid ratios were calculated.
      The ACE I/D polymorphism was detected by PCR. RESULTS: There were no significant
      differences of serum lipid ratios and blood pressure at baseline and before and
      after the HC/LF diet between the II genotype and the D carriers (ID and DD
      genotypes) in the whole study population, the males or the females separately.
      When compared with those before the HC/LF diet, all the subjects regardless of
      the genotype experienced statistical decreases of low density lipoprotein
      cholesterol/high density lipoprotein-cholesterol (LDL-C/HDL-C) and total
      cholesterol (TC)/HDL-C, but significant decrease of systolic blood pressure (SBP)
      was only found in the subjects with the II genotype. After taking into account
      gender, triglyceride (TG)/HDL-C and Log (TG/HDL-C) decreased in the males with
      theII genotype and increased in the female counterparts. The decreases of TC/HDL
      C and LDL-C/HDIL-C were observed in all the males and the female D carriers. SBP
      decreased only in the male D carriers. CONCLUSION: The interaction of the HC/LF
      diet with the I allele of the intron 16 I/D polymorphism at the ACE gene
      decreases TG/HDL-C and log (TG/HDL-C) in males, but increases TG/HDL-C and log
      (TG/HDL-C) in females in the Chinese young population. The interplay with the D
      allele lowers SBP in males, and TC/HDL-C and LDL-C/ HDL-C in females.

PMID- 24325102
TI  - [The study of interfering of endogenous VEGF-C genes and the protein expression
      gastric cancer cell with siRNA technique].
AB  - OBJECTIVE: To explore the interfering effects of siRNA on endogenous VEGF-C genes
      and the protein expression in gastric cancer cells. METHODS: Cultured gastric
      cancer cell line SGC7901 cells were prepared in vitro. Five siRNA primers of VEGF
      C were designed depending on the sequence of Accession No. BC035212. 1 in
      Genbank. After homology analysis, the primers were synthesized and transfected
      into SGC7901 cells. The endogenous VEGF-C mRNA level and its protein expression
      were observed. RESULTS: VEGF-C-siRNA was inserted into the gastric cancer cell
      successfully. Five siRNA primers of VEGF-C could inhibit VEGF-C genes and protein
      expression. CONCLUSION: siRNA could block the endogenous VEGF-C genes and the
      protein expression in gastric cancer cell.

PMID- 24325103
TI  - [The effect of tanshinone II A on the transmembrance action potential of
      myocardial cells in LQT2 rabbit models].
AB  - OBJECTIVE: To determine the effect of tanshinone II A on the transmembrance
      action potential of three layers of myocardial cells in LQT2 rabbit models.
      METHODS: Whole-cell patch clamp technique was used to record the action potential
      duration 90 (APD90) and the transmural dispersion of repolarization (TDR) of the
      epicardium, mid-myocardium and endocardium in the LQT2 rabbits. RESULTS: Of the
      three layers of myocardial cells, the mid-myocardium had the longest APD90 and
      the epicardium had the shortest APD90. The APD90 of all three layers of
      myocardial cells were shortened with infusion of 10 mg/mL tanshinone II A. Their
      TDR values also reduced by the infusion. CONCLUSION: Tanshinone II A shortens
      APD90 and reduces TDR values.

PMID- 24325104
TI  - [Effects of hypoxia preconditioning on serum NGB and S-100B in patients with
      intracranial aneurysm surgery].
AB  - OBJECTIVE: To study the clinical effects of hypoxia preconditioning (HPC) and its
      effects on serum neuroglobin (NGB) and S-100B level in the patients undergoing
      intracranial aneurysm surgery. METHODS: Forty patients scheduled to intracranial
      aneurysm surgery were randomly.divided into 2 groups: HPC group (n= 20) and
      control group (n= 20). The patients in HPC group were treated with 3 cycles of
      deoxidation-reoxygenation after intubation. The time of deoxidation in each HPC
      cycle was recorded, while vital signs were also recorded in each corresponding
      time point. Blood samples were obtained from exsanguinate radial artery and
      jugular bulb section at the end of each HPC cycle and corresponding time points
      during operation to measure serum level of NGB and S100B protein and to analysis
      blood gas. RESULTS: During HPC process, the patients in group HPC experienced
      mild hypoxia and CO2 retention. With the times of HPC increasing, CO2 retention
      degree became heavier (P<0. 05) while hypoxia improved, the patients need more
      time to make SpO2 from 100% to 90% (P<0. 05). From T2 to T4 (the end of the third
      reoxygenation, during skull opened and aneurysm dipped, skull closed), NGB in
      group HPC was higher than that in control (P<0. 05), but S-100B level was not
      different between HPC and control group (P>0. 05). CONCLUSION: HPC could induce
      compensatory ability of the body to hypoxia, which might be related to the up
      regulation of NGB expression.

PMID- 24325105
TI  - [Protective effect of ulinastatin on pulmonary function after cardiopulmonary
      bypass].
AB  - OBJECTIVE: To investigate the effects of Ulinastatin with different doses on
      pulmonary protection after cardiopulmonary bypass (CPB). METHODS: Ninety patients
      after CPB were brought into this study and divided into low doses Ulinastatin
      group (L group, n=30, 5 000 U/kg), high doses Ulinastatin group (H group, n=30,
      20 000 U/kg) and control group (C group, n= 30), respectively. When the patients
      were transferred into ICU after CPB, Ulinastatin was given intravenously to those
      in L and H group, while saline was given in C group. Blood samples were harvested
      at the time before the treatments (T0) and 12 hours (T1), 24 hours (T2) after the
      treatments, for the measurements of arterial pressure of oxygen (PaO2), arterial
      pressure of carbon monoxide (PaCO2),difference of alveoli-arterial oxygen
      pressure (PO(2A), oxygenation index (Ol),and tumor necrosis factor-alpha (TNF
      alpha) level. Pulmonary dynamic compliance (Cd), plat pressure (Pplat) and peak
      pressure (Ppeak) were determined at the time of To and wean (Tw). The durations
      of ventilation and intubation were recorded. RESULTS: At T0, the levels of PaO2,
      PaCO2, PO2A-a, OI and TNF-alpha in each group showed no significantly difference
      (P> 0. 05). At T1 and T2, the patients in H group had higher levels of PO2, PO2A
      a. and OI, lower level of TNF-alpha, shorter duration of ventilation and
      intubation than the patients in other two groups(P<0. 05). The parameters in L
      group were better than those in C group, but the differences were not stastically
      significant (P>0. 05). There was no significantly difference in the levels of Cd,
      Pplat, and Ppeak at T0 and Tw between any two groups (P>0. 05). The intubation
      and ventilation time in H group were shorter than that in L and C group (P<0.
      05). CONCLUSION: The application of Ulinastatin could achieve pulmonary
      protective effect after CPB, and it seems the effect could be better with high
      dose (20 000 U/kg) of Ulinastatin.

PMID- 24325106
TI  - [Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in penile
      cancer].
AB  - OBJECTIVE: To investigate the expression of thymidylate synthase (TS) and
      dihydropyrimidine dehydrogenase (DPD) in penile cancer. METHODS: A total of 96
      patients with penile cancer were included, the expression of TS and DPD in tumor
      tissues were examined by immunohistochemistry method, the relationship of TS and
      DPD expressions with the clinical characters were also analyzed. RESULTS: The
      expression of TS and DPD in penile cancer tissue were 41. 67% (40/96) and 33. 33%
      (32/96) respectively. There was a positive correlation between TS and DPD
      expression (Pearson C= 0. 362, P<0. 01). DPD was found to be more expressed in
      non-smoking patients (P = 0. 040). CONCLUSION: TS and DPD were moderately
      expressed in penile cancer and their expressions were positively correlated. This
      could be helpful for the application of fluorouracil in chemotherapy for the
      patients with penile cancer.

PMID- 24325107
TI  - [Differences in pathological features of histological inflammation between benign
      prostatic hyperplasia and prostate cancer].
AB  - OBJECTIVE: To study the pathologic features and differences of tissue
      inflammation in benign prostatic hyperplasia (BPH) and prostate cancer (PCa).
      METHODS: The HE stained slice obtained by prostate biopsy from 143 BPH and 106
      PCa were reviewed to determine whether the tissue inflammation existed. According
      to the histological classification of prostatic tissue inflammation, the features
      of tissue inflammation and the differences of these features between the two
      groups were studied in detail. RESULTS: There were 142 cases found tissue
      inflammation in 143 BPH patients and 104 cases in 106 PCa patients, so the
      incidences of tissue inflammation in BPH and PCa were 99. 3% and 98. 1%
      respectively. The anatomical location of inflammation was significant difference
      between BPH and PCa group (P<0. 05). The peri-glandular inflammation (56. 3%) was
      primary in BPH, and interstitial inflammation (56.7%) was the main pattern in
      PCa. The inflammation range was also significant difference between the two
      groups (P<0. 05). The inflammation was presented multifocally (60. 6%) in BPH,
      and focal lesions (51. 0%) was commonly found in PCa. Mild inflammation was most
      frequently observed in both groups (P>0. 05). However, there were statistically
      significant differences between the two groups in the degree of moderate and
      severe inflammation (P<0. 05). CONCLUSION: The incidences of tissue inflammation
      were high in both BPH and PCa, but the pathological features of tissue
      inflammation were different between BPH and PCa.

PMID- 24325108
TI  - [Comparing overnight dexamethasone suppression test, urine free cortisol, and
      midnight serum cortisol for the initial diagnosis of Cushing' s syndrome].
AB  - OBJECTIVE: To identify retrospectively the optimal cut-off points and the values
      of overnight dexamethasone suppression test, urine free cortisol, and midnight
      serum cortisol in the initial diagnosis of Cushing's syndrome in Chinese people.
      METHODS: The results of overnight low-dose dexamethasone suppression test (PTC
      DST), urine free cortisol (UFC) and late-night plasma total cortisol (PTC-24 h)
      of 102 patients who had clinically confirmed Cushing's syndrome and 102 patients
      without Cushing's syndrome were extracted from West China Hospital. Receiver
      operating characteristic (ROC) curves were drawn to identify optimal cut-off
      points of the three assays and their values in diagnosing Cushing' s syndrome.
      RESULTS: The optimal cut-off point (the point on the ROC curve closest to 1) for
      PTC-DST was set at 86 nmol/L, with 98. 7% sensitivity and 97. 2% specificity
      (100% sensitivity and 94. 4% specificity was achieved at 50 nmol/L 100%o
      sensitivity and 95. 8% specificity was achieved at 60 nmol/L). The optimal cut
      off point for PTC-24 h was set at 347 nmol/L, with 93. 4% sensitivity and 98. 4%
      specificity (98. 9% sensitivity and 85. 2% specificity was achieved at 207
      nmol/L). The optimal cut-off point for UFC was set at 230. 15 icrog/24 h, with
      92. 2 sensitivity and 95. 7% specificity (96. 1% sensitivity and 85. 1%
      specificity was achieved at 127. 55 microg/24 h). There was no significant
      difference between PTC-DST and PTC-24 h in the areas under the ROC curves,
      whereas both had a greater area under the ROC curve than that of UFC (P< 0. 05).
      CONCLUSION: Compared with the recommended 50 nmol/L cut-off point for PTC-DST in
      the USA and the European countries, the same sensitivity and a higher specificity
      can be achieved at a cut-off at 60 nmol/L for the Chinese people. PTC-DST and PTC
      24 h have similar values in the initial diagnosis of Cushing's syndrome, but PTC
      DST is more convenient to be used in outpatient environment.

PMID- 24325109
TI  - [Change and correlated factors of fasting level of the plasma endotoxin in
      subjects with different glucose tolerances and body mass indices].
AB  - OBJECTIVE: To investigate the change of the levels of fasting plasma endotoxin
      (ET) and assess its correlated factors in individuals with different glucose
      tolerances and body mass indices. METHODS: The levels of fasting plasma ET were
      assayed by the endpoint chromogenic limulus amebocyte lysate method in subjects
      with type 2 diabetes (T2DM), impaired glucose regulation (IGR) and normal glucose
      tolerance (NGT). The height, body mass, waist, hips, systolic blood pressure and
      diastolic blood pressure were measured with the conventional methods; body mass
      index (BMI) and waist hip ratio (WHR) were calculated. All groups were divided
      into obesity (BMI>or=25 kg/m2) and non-obesity (BMI<25 kg/m2) subgroups. The
      levels of fasting blood glucose (FBG), 2 hours plasma glucose (2 hPG), fasting
      insulin (FINS), postprandial insulin (PINS), hemoglobin Alc (HbAlc), blood
      lipids, free fatty acids (FFA), serum aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) were also analyzed, and homeostasis model
      assessment of insulin resistance (HOMA-IR) was calculated. The relationship of
      the levels of plasma ET with age, BMI, WHR, blood pressure, FBG, 2 hPG, FINS,
      PINS, HOMA-IR, HbA1c, blood lipids, FFA, AST and ALT were also analyzed. RESULTS:
      (1) The levels of plasma ET in T2DM group (n=37) was significantly higher than
      that in NGT group (n=37) [7. 1 (3. 7-11. 8) EU/mL vs. 4. 5 (2.2-6.3) EU/mL,
      P<0.05]. The levels of plasma ET in IGR group (n=23) C5.0 (2.4-10.3) EU/mLU was
      lower than that in T2DM group and higher than NGT group but the differences were
      not significant (P>0. 05). (2) The levels of plasma ET in the obesity T2DM
      subgroup was higher than that in the non-obesity T2DM subgroup but the
      differences were not significant [7. 3 (3. 8-13. 3) EU/mL vs. 7.0 (3. 6-10. 4)
      EU/mL, P>0. 05]. There was a remarkable difference in the levels of plasma ET
      between obesity and non-obesity subgroup of IGR (6.8 (2.9-13.2) EU/mL vs. 2.7
      (1.6-5. 5) EU/mL, P<0. 05), similarly between obesity and non-obesity subgroup of
      NGT (6.2 (3. 4-12. 7) EU/mL vs. 2. 8 (1. 8-4. 9) EU/mL, P<0. 05). (3) Multiple
      linear regression analysis demonstrated that ET wasn' t the important factor
      influencing FBG and 2 hPG. But BMI and FBG were the important factors influencing
      ET. 2 hPG and WHR weren't the important factors influencing ET. CONCLUSION: With
      the increase in glucose metabolic abnormalities and BMI, the levels of plasma ET
      are gradually increased. ET isn't the important factor influencing FBG and 2 hPG.
      BMI and FBG are the important factors in influencing ET.

PMID- 24325110
TI  - [The changes of gastrointestinal hormones GLP-1, PYY and ghrelin in patients with
      newly diagnosed type 2 diabetes mellitus].
AB  - OBJECTIVE: To study the changes of plasma glucagon-like peptide-1 (GLP-1), serum
      peptide-YY (PYY) and Ghrelin and their secretion functions in patients with newly
      diagnosed type 2 diabetes mellitus (T2DM). METHOD: A total of 102 subjects were
      enrolled, including 32 normal-glucose-tolerance controls (NGT) and 70 patients
      with newly diagnosed T2DM. Height, body mass, waist circumference (WC) and hip
      circumference were measured. The plasma lipids and 0 h, 1/2 h, 2 h plasma
      glucose, insulin (INS), GLP-1, serum PYY and Ghrelin in a standard meal test in
      each subject were detected, and body mass index (BMI), homeostasis model
      assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI),
      homeostasis model assessment of beta cell function (HOMA-B) and early insulin
      secretion function index (DeltaI30/DeltaG30) were calculated. All these variables
      were compared between the two groups. RESULTS: Compared with those in NGT group,
      the WC, fasting plasma glucose (FPG), postprandial plasma glucose (2 h-PG),
      triglyceride (TG), HOMA-IR were significantly higher (P 0.05), while INS(30),
      HOMA-B, ISI, DeltaI30/DeltaG30 were significantly lower in T2DM group (P<0. 05).
      In addition, in T2DM group, 0 h, 1/2 h, 2 h plasma GLP-1 and serum PYY and the
      area under the curve (AUC) of GLP-1 (GLP-lAuc ) and PYY (PYYAc) in standard meal
      test were significantly lower (P<0. 05), but the serum Ghrelin and GhrelinA, were
      significantly higher (P<0. 05). Meanwhile, the secretory peak of GLP-1 and PYY
      after standard meal in T2DM patients all disappeared. In T2DM group, PYYAUC and
      TG were negatively correlated (P<0.05), the fasting serum Ghrelin level was
      negatively associated with total cholesterol (TC), and GhrelinAuc was positively
      associated with HOMA-B, but negatively with the low-density lipoprotein
      cholesterol (LDL-C) and FPG (P(<0. 05). CONCLUSION: Patients with newly diagnosed
      T2DM have decreased fasting and postprandial GLP-1 and PYY levels, along with
      changes of their secretion mode and increased levels of Ghrelin.

PMID- 24325111
TI  - [The curative effect of task-oriented approach in combination with articulation
      approach on spastic dysarthria].
AB  - OBJECTIVE: To assess the effectiveness of task-oriented approach in treating
      patients with spastic dysarthria. METHODS: A randomized control trial was
      undertaken in 44 inpatients diagnosed with spastic dysarthria at the Department
      of Rehabilitation Medicine in West China Hospital. All of the participants
      received basic medical therapy, occupational therapy, physical therapy, and an
      articulation approach for speech therapy by a professional speech therapist over
      a one month period. A task-oriented approach was added to the speech therapy
      regime of the test group of participants by another professional speech therapist
      over the same period of time. The outcomes of speech therapy were measured by the
      Frenchay dysarthria assessment (FDA). RESULTS: Significant improvements were
      found in the test group in relation to 15 FDA items, such as dribbling, lips
      spread, and palate maintenance (P<0. 05). The performance of the participants in
      the test group on the rest of FDA items also demonstrated an improvement trend
      compared with that of the controls (P>0. 05) except for the three items in
      relation to cough, lips at rest and jaw in speech. CONCLUSION: Task-oriented
      approach for speech therapy is effective in treating patients with spastic
      dysarthria. A task-oriented approach in combination with an articulation approach
      can produce better patient outcomes compared with the articulation approach
      alone. Further studies are warranted.

PMID- 24325112
TI  - [Low-dose of furosemide to correct oliguria in gynecological surgery].
AB  - OBJECTIVE: To investigate the safety and efficay of low-dose furosemide in the
      correction of oliguria in the patients undergoing gynecologic surgery. METHODS: A
      total of 120 patients, aged between 20 to 50 years old, who were scheduled to
      receive elective gynecological open surgery under general anesthesia, were
      randomly divided into 3 groups: the control group, furosemide 0. 05 mg/kg (F0.5)
      group and furosemide 0. 1 mg/kg (F1) group (n=40). During surgery, blood volume
      and blood pressure was maintained in the normal range. The urine volume was
      recorded every 30 minutes. Oliguria was defined as the urine volume less than 0.
      5 mL/(kg . h), When oliguria was observed, flurosemide or saline was given to the
      patients based on the enrollment status. If the patients were still oliguric 30
      min later, the treatment was repeated. The total time of surgery, net fluid
      infusion volume, urine volume per unit time per body weight at the completion of
      surgery, the incidence of intraoperative oliguria, the total amount of furosemide
      and the average specific gravity of urine were recorded. RESULTS: There was no
      statistically significant difference in sex, age, fasting time, the total time of
      surgery and intraoperative net fluid infusion volume among the three groups (P>0.
      05). The urine volume per unit time per body weight in control group was
      significantly lower than that of the other two groups (P<0. 01). The incidence of
      intraoperative oliguria in the three groups (control, low dose, high dose groups)
      were 52. 5%, 12. 5% and 0%, respectively (P<0. 01). CONCLUSION: Low-dose of
      furosemide could maintain normal urine volume and specific gravity of urine
      during gynecological surgery.

PMID- 24325113
TI  - [Three-dimensional finite element analysis of acetabular prosthesis in an adult
      patient with total flip arthroplasty for high dislocation].
AB  - OBJECTIVE: To observe stress distributions around the acetabular prosthesis and
      the bones of a patient who underwent total hip arthroplasty (THA). METHODS:
      Finite element analysis (FEA) was performed with an osteoarthritis patient who
      underwent THA for her secondary hip high dislocations: Scenario A--deepened
      acetabulum at the true acetabulum with a small 44 mm cup; Scenario B--structural
      bone graft at lateral acetabular with a 48 mm cup; Scenario C--place tantalum
      metal acetabular reconstruction at the lateral acetabular with a 48 mm cup;
      Scenario D--the normal side of the hip. According to the Wasielewski methods,
      acetabular was divided into four zones, in the same way on the lining surface.
      Ten points were taken in each zone for measuring the Von Mises stress values.
      RESULTS: Scenario A generated significantly greater stress values in the bones in
      zone one than the other three scenarios. Significantly greater stress was also
      found in the inner surface of polyethylene over all of the four zones under
      scenario A compared with those of the scenario B and C, especially in zone one
      and two. The cup initial micro-mobility for scenario A was 49. 18 microm, 19
      times of that of scenario B and 8 times of that of scenario C. CONCLUSION: (1)
      Deepened acetabulum with small cup can cause stress concentration in the
      acetabular bones and liner, leading to large cup initial micro-mobility. (2)
      Acetabular lateral structural bone grafting and placement of tantalum metal
      reconstruction have better biomechanical properties, which can enable the use of
      bigger cups.

PMID- 24325114
TI  - [Comprehensive understanding and study on idiopathic inflammatory myopathies to
      improve its diagnosis and treatment].
AB  - Idiopathic inflammatory myopathies(IIM) are a group of autoimmune diseases
      characterized by muscle inflammation and progressive weakness. Diagnosis of IIM
      relies on the combination of clinical manifestation, blood biochemical
      indicators, myositis specific antibodies, electromyogram and pathology of muscle.
      Classification criteria of IIM keeps developing, and different criteria has
      different value on clinical application. IIM may involve important organs such as
      skin, joint, cardiac muscle and lung, except for skeletal muscle. Internal organs
      involvement should be evaluated and predicted, which could help to improve the
      prognosis of IIM. It is necessary to evaluate the disease activity objectively
      and accurately, which now could be accomplished with uniform and standardized
      clinical assessment system established by international organizations as the
      International Myositis Assessment and Clinical Studies Group. The immune
      pathological progress of IIM has already been well-known but the pathogenesis
      mechanism needs further study. Comprehensive evaluation of disease activity and
      organ damage need be emphasized before the beginning of treatments. Treatment
      strategies should be individualized, and the side effects of therapeutic drugs
      should be monitored. Multidisciplinary collaboration contributes to the
      improvement of diagnosis and therapy for IIM.

PMID- 24325115
TI  - [Comparison of four diagnostic criteria for idiopathic inflammatory myopathy].
AB  - OBJECTIVE: To compare the clinical values of four different criteria for
      diagnosing idiopathic inflammatory myopathy (IIM). METHODS: The four different
      criteria published in 1975, 1995, 1997 and 2004 were applied to 94 IIM patients
      and 98 patients with other myopathies in West China Hospital. RESULTS: The
      sensitivity of the four criteria for diagnosing IIM was 56. 4% (1975), 87. 2%
      (1995), 61.7 % (1997), and 52. 1% (2004) respectively. The specificity of the
      four criteria for diagnosing IIM was 78. 6% (1975), 20. 4% (1995), 78. 6% (1997),
      and 90. 8% (2004) respectively. The Youden index was 35.0% (1975), 7.6% (1995),
      40. 3% (1997), and 42.9% (2004), with an odd product of 4. 74 (1975), 1. 75
      (1995), 5. 91 (1997) and 10. 77 (2004) respectively. The Kappa value of the four
      criteria was 0. 351 (1975, P<0.05), 0. 075 (1995, P>0. 05), 0. 404 (1997, P<0.05
      ) and 0. 433 (2004, P<0.05), and their area under the ROC curve was 0. 675 (1975,
      P=0. 00), 0. 538 (1995, P=0.36),0. 701 (1997, P=0.00) and 0. 715 (2004, P=0.00)
      respectively. CONCLUSION: The 2004 criteria have a better value in diagnosing
      IIM.

PMID- 24325116
TI  - [Risk factors associated with cardiac involvement in patients with
      dermatomyositis/polymyositis].
AB  - OBJECTIVE: To identify risk factors associated with cardiac involvement (CI) in
      patients with dermatomyositis/polymyositis (DM/PM). METHODS: Medical records of
      129 DM/PM patients were reviewed retrospectively. The risk factors associated
      with CI in those patients were screened through Xt tests or independent tests
      before a multivariate logistic regression analysis was performed. ROC curves were
      constructed to determine diagnostic values of the identified risk factors.
      RESULTS: CI occurred in 59 (45. 74%) of DM/PM patients, with 41 (69. 49%) showing
      electrocardiographic (ECG) abnormality; 25 (42. 37%) showing ultrasonic
      cardiogram (UCG) abnormality; 8 (13. 56%) being diagnosed with heart failure, and
      2 (3. 39%) being diagnosed with myocardial infarction. Eight (13.56%) of the
      patients with CI died. CI was more likely to occur in patients with an older age,
      having interstitial lung disease, antinuclear antibody (ANA) positive, and anti
      Jo-1 antibody positive (P<0.05). The logistic regression analysis revealed that
      interstitial lung disease (beta=1. 554), aspartic aminotransferase/creatine
      kinases (AST/CK) ratio (beta=1.189), positive ANA (beta= 1. 172) and age
      (beta=0.042) were risk factors associated with CI (P<0. 05). Notable areas under
      ROC curve (0. 642) was found for AST/CK in determining CI in DM/PM patients (P<0.
      05), albeit with low accuracy. A cut-off of AST/CK ratio at 0. 312 was identified
      as a reference point for determining CI in patients with DM/PM. CONCLUSION:
      Cardiac involvement is the most common complication of DM/PM, although the
      majority are subclinical. ECG and UCG are common tools for diagnosing cardiac
      involvement. Interstitial lung disease, AST/CK ratio, positive ANA and age are
      predictors of CI in DM/PM patients.

PMID- 24325117
TI  - [Clinical features and risk factors associated with interstitial lung disease in
      patients with classic dermatomyositis or clinical amyopathic dermatomyositis].
AB  - OBJECTIVE: To investigate the clinical features and risk factors associated with
      interstitial lung disease (ILD) in patients with classic dermatomyositis (classic
      DM) or clinical amyopathic dermatomyositis (CADM). METHODS: Medical records of
      121 DM patients (77 with classic DM and 44 with CADM) were reviewed
      retrospectively. The risk factors associated with ILD were identified through
      Binary Logistic Regression analyses. RESULTS: ILD presented in 40. 3% (31/77) of
      patients with classic DM and 50. 0% (22/44) of patients with CADM. Overall, the
      DM patients had a prevalence of ILD of 43. 8%. Univariate analyses showed that
      arthralgia, cough, dyspnea, anti-Jo-1 antibody, malignant tumors, and the levels
      of Erythrocyte sedimentation rate (ESR) and Albumin (ALB) were associated with
      ILD. The Multivariate Logistic Regression analysis identified arthralgia (beta=
      1. 119, P= 0. 023), cough (beta= 2. 423, P= 0. 003) and ESR (beta= 0. 041, P= 0.
      009) as risk factors of ILD. CONCLUSION: ILD is a common complication of classic
      DM/CADM and arthralgia, cough and high level of ESR are independent risk factors
      of ILD.

PMID- 24325118
TI  - [Idiopathic inflammatory myopathies complicated with pneumonias: clinical
      characteristics and pathogen analysis].
AB  - OBJECTIVE: To investigate the clinical characteristics, pathogen constitution and
      their tolerance to antibiotics in idiopathic inflammatory myopathies (IIM)
      patients complicated with pneumonia and the associated risk factors. METHODS: The
      clinical data and pathogen test results of 93 IIM patients with pneumonia and 52
      IIM patients without pneumonia (control group) were retrieved and compared.
      RESULTS: Age of onset and interstitial lung disease were identified as risk
      factors associated with IIM complicated with pneumonia. Gram negative bacteria
      were the most common pathogen. Klebsiella pneumoniae was the most common bacteria
      and Candida albicans was the most common fungus causing infections in the IIM
      patients, which were relatively sensitive to the third- and fourth-generation of
      antibiotics such as cephalosporin, fluoroquinolones and aminoglycoside.
      CONCLUSION: Older patients with interstitial lung disease are prone to having
      pneumonia, especially those caused by gram negative bacteria and other atypical
      pathogens. Timely and reasonable anti-infection treatment is essential.

PMID- 24325119
TI  - [Levels of acute-phase-reactants in patient with dermatomysitis and its
      correlations with IL-6 and dermatomyositis disease activity].
AB  - OBJECTIVE: To determine the association between acute-phase-reactants (APR) and
      interleukin-6 (IL-6) in patient with dermatomysitis (DM). METHODS: The levels of
      C-reactive protein (CRP), serum amyloid A protein(SAA) and serum ferritin (SF) in
      peripheral blood of 31 adult DM patients were determined by chemiluminescence
      immunoassay, and compared with those of 23 patients with systemic lupus
      erythematosus (SLE), 22 patients with rheumatoid arthritis (RA), and 18 patients
      with Sjagren syndrome (SS). The correlations between the levels of those APR and
      IL-6 were examined. We also measured dermatomyositis disease activity using
      myositis disease activity assessment tool (MDAAT), and examined its association
      with APR levels. RESULTS: DM patients had significantly lower level of CRP [(17.
      08 +/- 17. 18) mg/L] than those patients with RA [(85. 95 +/-60.62) mg/L, P<0.
      000 1], SLE [(51. 34+/-52. 98) mg/L, P=0. 006] and SS [(47. 00+/-47. 24) mg/L, P=
      0.018]. DM patients had significantly lower level of SAA [(92. 04 +/- 98. 93)
      mg/L] than those patients with RA [(311.30 +/- 292. 45) mg/L, P= 0. 002] and SS
      [(284. 31 +/- 325. 30) mg/L, P= 0. 025]. DM patients had significantly higher
      level of SF [(510. 10 +/- 610. 73) ng/mL] than those patients with SS [(220. 33
      +/- 164. 07) ng/ mL, P=0. 02], as well as those with RA and SLE albeit without
      statistical significance. All of the three APRs were positive correlated with IL
      6 level. No significant associations between APR and systemic or global disease
      activities were found, although CRP was associated with constitutional disease
      activity and SF was associated with pulmonary disease activity. CONCLUSION: DM
      patients have lower levels of elevated APR than the other three common connective
      tissue diseases, which is associated with IL-6 but not with global disease
      activity.

PMID- 24325120
TI  - [Survival analysis and risk factors for survival in idiopathic inflammatory
      myopathies: a retrospective cohort study].
AB  - OBJECTIVE: To study predominant risk factors for survival in idiopathic
      inflammatory myopathies (JIM). METHODS: The clinical data of 163 cases of IIM
      were reviewed, who received the diagnosis and treatments in West China Hospital
      from January 1997 to December 2010. Kaplan-Meier survival curve was used for the
      survival analysis of these patients with IIM. Univariate and multivariate
      analysis of risk factors for survival in the patients with IIM were carried out
      by Log-rank test, univariate Cox regression analysis and Cox regression model
      respectively. RESULTS: There were 21 death occured among 163 patients with IIM,
      and the estimated 3, 5, 10-year survival rate was 93%, 89%, 80% respectively. The
      mortality of the patients with dermatomyositis (DM) or amyophathic
      dermatomyositis(ADM) increased significantly when compared with polymyositis (PM,
      P=0. 033, P= 0. 06). The mortality of IIM patients complicated with tumor or
      cadiovascular involvement was much higher than that of those patients without any
      complications (P<0. 001, P=0. 015). Tumor and cadiovascular involvement were two
      independent risk factors for the survival of IIM individuals. CONCLUSION: DM and
      ADM have much unfavorable prognosis than PM. Tumor and cadiovascular involvement
      are two major risk factors for the survival of IIM patients.

PMID- 24325121
TI  - [Expression of Gphaq in peripheral blood T lymphocytes of patients with
      polymyositis and its correlation with disease activity].
AB  - OBJECTIVE: To analyze the expression of Gaq in peripheral blood T lymphocytes of
      the patients with polymyositis (PM) and its correlation with disease activity
      evaluated by the clinical markers [manual muscle test (MMT),myositis disease
      activity assessment (MDAA),creatine phosphokinase (CK), erythrocyte sedimentation
      rate (ESR), C-reactive protein (CRP)]. METHODS: Blood samples were obtained from
      30 patients with first onset PM and 30 healthy volunteers. Peripheral blood
      mononuclear cells (PBMCs) from these patients were collected and CD3+ T cells
      from PBMCs were sorted out with magnetic beans. The mRNA and protein expression
      levels of Galphaq in T cells were measured by RT-PCR and Western blot. Student's
      unpaired 2-tailed t-test was applied to identify Galphaq expression difference
      between PM patients and healthy controls. Pearson's correlation between Galphaq
      mRNA expression of PM and clinical evaluation markers MMT, MDAA, CK, ESR or CRP
      was determined. RESULTS: Compared to health control, PM patients had
      significantly lower expression levels of Galphaq protein and mRNA in peripheral
      blood CD3+ T cells (P<0. 001). Negative correlation was found between Galphaq
      mRNA level and MMT (r= -0. 704, P<0. 001), MDAA (r= -0. 793, P<0. 001) or CK (r= 
      0. 670, P<0. 001), and no correlation was found between Galphaq mRNA level and
      ESR or CRP. CONCLUSION: Galphaq expression in T cells of PM is lower than that in
      normal control and has negative correlation with PM disease activity.

PMID- 24325122
TI  - [A comparison of magnetic resonance spectroscopy and diffusion weighted imaging
      for diagnosing prostate cancer].
AB  - OBJECTIVE: To compare the clinical values of magnetic resonance spectroscopy
      (MRS) and diffusion weighted imaging (DWI) in diagnosing prostate cancer.
      METHODS: A 1. 5T MR scanner was used in this study. We measured 274 regions of
      interest (ROI) in the images produced by MRS and DWI from 53 patients. The biopsy
      confirmed 150 ROI as cancers and 124 ROI as non-cancers. The results of MRS and
      DWI were compared using receiver operating characteristic (ROC) curves. RESULTS:
      Significant differences (P<0. 05) between malignant and benign tumors were found
      in signal intensity (b= 0,100,800 s/mm, in DWI), ADC value(in DWI), Cit content
      integral, Cho content integral and (Cho+Cr)/Cit ratio (in MRS). The ROC curves
      showed that ADC value, signal intensity (b=800 s/mm2) and the ratio of
      (Cho+Cr)/Cit performed better in distinguishing prostate cancers from benign
      tumors. The optimal operating point (OOP) of ADC value was determined as 1. 027 x
      10(-3) mm2/s, with 0. 887 specificity, 0. 953 sensitivity, 0. 84 Youden index,
      and the area under curve (AUC) of 0. 966. The OOP of signal intensity (b=800
      s/mm2) was determined as 47. 1, with 0. 806 specificity, 0. 72 sensitivity, 0. 53
      Youden index, and the AUC of 0.782; The OOP of (Cho+Cr)/Cit ratio was determined
      as 0.78, with 0. 806 specificity, 0. 793 sensitivity, 0. 60 Youden index, and the
      AUC of 0. 844. CONCLUSION: DWI is a better method than MRS in differentiating
      prostate cancers from benign tumors.

PMID- 24325123
TI  - [Open high tibial osteotomy through small incision with annular external fixator
      for treating genu varum deformity].
AB  - OBJECTIVE: To evaluate the outcomes of open high tibial osteotomy through small
      incision with annular external fixator for treating genu varum deformity.
      METHODS: We reviewed 8 cases of open high proximal tibia osteotomy through small
      incision with annular external fixator for patients (10 knees) with genu varum
      due to high tibia varum. The patients were followed up 1, 2, 3, 6, 12, 24 and 36
      months after the operations. Data about infection, healing, varus angle, knee
      distance and Insall-Salvati index were retrieved and analysed. RESULTS: The
      patients had a mean varus angle of 15. 3 degrees +/- 2. 3 degrees (range, 10
      degrees - 28 degrees) before the operations. The operations were all recorded as
      successful following a (29. 3 +/- 3. 1) month (range, 24-36 months) post
      operation follow-up, with external fixator remaining stable and no instrument
      failures. The bones were healed at an average of (11. 2 +/- 1. 5) weeks (range, 8
      12 weeks) and there was no nonunion or delayed union. The operations reduced
      varus angle of the knees to - 1. 1 degrees +/- 0. 6 degrees (range, - 7 degrees -
      3 degrees ), indicating a significant improvement compared to that of the
      preoperations. There were 2 cases of superficial pin infections. CONCLUSION: Open
      high tibial osteotomy through small incision with annular external fixator has
      good fixation stability and satisfactory clinical outcomes with little
      complications for treating patients with genu varum deformity.

PMID- 24325124
TI  - [A comparison of 2-flap and sommerlad in surgical repair of cleft palate].
AB  - OBJECTIVE: To compare 2-flap and Sommerlad in surgical repair of cleft palate.
      METHODS: 30 patients with cleft palate were equally divided into two groups. One
      group accepted sommerlad operation (9 unilateral complete and 6 incomplete
      cases); the other group accepted 2-flap operation (10 unilateral complete and 5
      incomplete cases). RESULTS: Sommerlad operation lasted longer than 2-flap
      operation, but without statistical significance (P>0. 05). The two types
      operations produced similar functional recovery (P>0. 05). The Sommerlad
      operation had less intraoperation blood loss and left softer palate scars than
      the 2-flap operation (P<0. 05). CONCLUSION: Sommerlad operation and 2-flap
      operation are both effective. Different methods should be considered based on the
      abnormal situation of patients and the operation proficiency of the surgeons.

PMID- 24325125
TI  - Adaptive differentiation of traits related to resource use in a desert annual
      along a resource gradient.
AB  - * Plant resource-use traits are generally hypothesized to be adaptively
      differentiated for populations distributed along resource gradients. Although
      nutrient limitations are expected to select for resource-conservative strategies,
      water limitations may select for either resource-conservative or -acquisitive
      strategies. We test whether population differentiation reflects local adaptation
      for traits associated with resource-use strategies in a desert annual (Helianthus
      anomalus) distributed along a gradient of positively covarying water and nutrient
      availability. * We compared quantitative trait variation (Q(ST)) with neutral
      genetic differentiation (F(ST)), in a common garden glasshouse study, for leaf
      economics spectrum (LES) and related traits: photosynthesis (A(mass), A(area)),
      leaf nitrogen (N(mass), N(area)), leaf lifetime (LL), leaf mass per area (LMA),
      leaf water content (LWC), water-use efficiency (WUE, estimated as delta(13)C) and
      days to first flower (DFF). * Q(ST)-F(ST) differences support adaptive
      differentiation for Amass , N(mass), N(area), LWC and DFF. The trait combinations
      associated with drier and lower fertility sites represent correlated trait
      evolution consistent with the more resource-acquisitive end of the LES. There was
      no evidence for adaptive differentiation for A(area), LMA and WUE. * These
      results demonstrate that hot dry environments can selectively favor correlated
      evolution of traits contributing to a resource-acquisitive and earlier
      reproduction 'escape' strategy, despite lower fertility.

PMID- 24325126
TI  - Saturation behavior in X-ray Raman scattering spectra of aqueous LiCl.
AB  - We report a study on the hydrogen-bond network of water in aqueous LiCl solutions
      using X-ray Raman scattering (XRS) spectroscopy. A wide concentration range of 0
      17 mol/kg was covered. We find that the XRS spectral features change
      systematically at low concentrations and saturate at 11 mol/kg. This behavior
      suggests a gradual destruction in the hydrogen-bond network until the saturation
      concentration. The surprisingly large concentration required for the saturation
      supports an interpretation in which the ions affect the structure of water only
      within their first hydration shell. The study is complemented by density
      functional-theory calculations and molecular dynamics simulations. 

PMID- 24325127
TI  - Novel therapeutic options for multiple sclerosis.
AB  - Multiple sclerosis (MS) is considered as an autoimmune disorder of the CNS with
      neuro-inflammatory and neurodegenerative components. We review here the
      innovative drugs recently registered and those in clinical development for MS.
      Immunomodulation has been the preferred therapeutic approach for MS since the
      first IFN-beta was registered in the 1990s. Several immunomodulators are now
      available, which show a high efficacy in reducing the number of relapses in
      patients with the relapsing-remitting form of MS (RRMS). The high efficacy of
      most immunomodulators is, however, associated with substantial safety risks,
      notably concerning infections or cancers. Recently oral drugs have been approved
      for RRMS; however, biologics, and notably, monoclonal antibodies are still well
      represented in the development pipelines. An unmet medical need remains the
      treatment of the primary and secondary forms of MS or chronic progressive MS
      (CPMS). Half a dozen immunomodulators with proven efficacy in RRMS are now
      undergoing evaluation in Phase III trials in the CPMS indication. Neuroprotective
      drugs that prevent demyelination and/or improve remyelination would be
      interesting for CPMS, but these drugs are currently in the early development
      phase and their efficacy has not been demonstrated yet.

PMID- 24325128
TI  - GyneScan: an improved online paradigm for screening of ovarian cancer via tissue
      characterization.
AB  - Ovarian cancer is the fifth highest cause of cancer in women and the leading
      cause of death from gynecological cancers. Accurate diagnosis of ovarian cancer
      from acquired images is dependent on the expertise and experience of
      ultrasonographers or physicians, and is therefore, associated with inter observer
      variabilities. Computer Aided Diagnostic (CAD) techniques use a number of
      different data mining techniques to automatically predict the presence or absence
      of cancer, and therefore, are more reliable and accurate. A review of published
      literature in the field of CAD based ovarian cancer detection indicates that many
      studies use ultrasound images as the base for analysis. The key objective of this
      work is to propose an effective adjunct CAD technique called GyneScan for ovarian
      tumor detection in ultrasound images. In our proposed data mining framework, we
      extract several texture features based on first order statistics, Gray Level Co
      occurrence Matrix and run length matrix. The significant features selected using
      t-test are then used to train and test several supervised learning based
      classifiers such as Probabilistic Neural Networks (PNN), Support Vector Machine
      (SVM), Decision Tree (DT), k-Nearest Neighbor (KNN), and Naive Bayes (NB). We
      evaluated the developed framework using 1300 benign and 1300 malignant images.
      Using 11 significant features in KNN/PNN classifiers, we were able to achieve
      100% classification accuracy, sensitivity, specificity, and positive predictive
      value in detecting ovarian tumor. Even though more validation using larger
      databases would better establish the robustness of our technique, the preliminary
      results are promising. This technique could be used as a reliable adjunct method
      to existing imaging modalities to provide a more confident second opinion on the
      presence/absence of ovarian tumor. 

PMID- 24325129
TI  - A review of kidney motion under free, deep and forced-shallow breathing
      conditions: implications for stereotactic ablative body radiotherapy treatment.
AB  - Motion management strategies are important during stereotactic ablative body
      radiotherapy for abdominal targets. The kidney is a mobile retroperitoneal organ
      that moves with respiration. A review of the literature was performed to
      investigate the reported degree of kidney motion associated with various
      breathing conditions. A structured search was performed using Medline from
      January 1970 to May 2013 for all publications describing cranial-caudal kidney
      motion. Relevance to radiotherapy practice was reviewed based on any breathing
      instructions and/or immobilization equipment that could affect breathing pattern.
      Studies were categorized under three types of breathing conditions: Forced
      shallow, breath-hold/deep and free. A total of 25 publications were identified
      describing cranial-caudal kidney motion with a combined total of 415
      participants. Three publications described forced-shallow breathing using prone
      positioning or abdominal compression plates. Prone positioning, compared to
      supine positioning, did little to minimise kidney motion, however use of
      compression plates can result in kidney motion of less than 5 mm. Eight
      publications described deep breathing/breath hold techniques that showed average
      kidney motion ranging between 10 mm-40 mm. Fifteen publications investigated
      kidney motion under free breathing with the majority reporting mean motion of
      less than 10 mm. Kidney movement of up to 8.1 mm in the anterior posterior
      direction and 6.2 mm laterally were reported with no indications that breathing
      technique can influence the extent of this motion. In summary, kidney movement is
      complex and consideration should be made to ensure that motion management
      strategies provide the desired radiotherapy benefit. There are limited
      publications on the effectiveness of abdominal compression on reducing kidney
      motion which warrant further investigation in this area. 

PMID- 24325130
TI  - Dosimetric characteristics of a PIN diode for radiotherapy application.
AB  - The PIN diode developed by Bhabha Atomic Research Centre (BARC) was modified for
      its use as a dosimeter in radiation therapy. For this purpose the diode was
      mounted on a printed circuit board (PCB) and provided with necessary connections
      so that its response against irradiation can be recorded by a standard
      radiotherapy electrometer. The dosimetric characteristics of the diode were
      studied in Co-60 gamma rays as well as high energy X-rays. The measured
      sensitivity of this PIN diode is 4 nC/cGy which is about ten times higher than
      some commercial diode dosimeters. The leakage current from the diode is 0.04 nA.
      The response of the PIN diode is linear in the range of 20-1000 cGy which covers
      the full range of radiation dose encountered in radiotherapy treatments. The non
      linearity of the diode response is 3.5% at 20 cGy and it is less than 1.5% at
      higher dose values. Its repeatability is within 0.5%. The angular response
      variation is about 5.6% within 6608 with respect to normal beam incidence. The
      response of the PIN diode at 6 and 18 MV X-rays varies within 2% with respect to
      its response at Co-60 gamma rays. The source to surface distance (SSD) dependence
      of the PIN diode was studied for Co-60 beam. It was found that the response of
      the diode decreases almost linearly relative to given dose for beams with
      constant collimator setting but increasing SSD (decreasing dose-rate). Within
      this study the diode response varied by about 2.5% between the maximum and
      minimum SSD. The dose-rate dependence of the PIN diode for 6 and 15 MV-rays was
      studied. The variation in response of diode for both energies in the studied dose
      range is less than 1%. The field size dependence of the PIN diode response is
      within 1% with respect to the response of ionisation chamber. These studies
      indicate that the characteristics of the PIN diode are suitable for use in
      radiotherapy dosimetry. 

PMID- 24325131
TI  - Combination of cetuximab and rapamycin enhances the therapeutic efficacy in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide. It is
      well known that the activation of PI3K/AKT/mTOR and the Ras/MAPK signaling
      pathway plays a critical role in cellular metabolism, growth and proliferation,
      and its inhibitors have been used as therapeutic drugs for hepatocellular
      carcinoma. Cetuximab, a chimerical monoclonal EGFR IgG1 antibody, can block the
      binding of EGF or other ligands to EGFR and thus inhibit ligands-induced receptor
      phosphorylation. In the present study, we found that rapamycin could enhance the
      antiproliferation effect of cetuximab in both HepG2 cells and Huh-7 cells and
      arrest the cell cycle. Cetuximab in combination with rapamycin had synergistic
      effects on inhibiting the phosphrylation of proteins in PI3K/AKT/mTOR and
      Ras/MAPK signaling pathway. Combination of cetuximab with rapamycin treatment
      significantly suppressed the HCC development in HepG2 cells-xenografted mice and
      improved the survival. Cetuximab and rapamycin inhibited the growth of HCC both
      in vitro and in vivo. These results suggest that the combination therapy using
      the inhibitors for both EGFR and PI3K/AKT/mTOR signaling pathways may be a novel
      therapeutic approach for HCC. 

PMID- 24325132
TI  - Refractory malignant fibrous histiocytoma: CT-guided treatment with a
      multidisciplinary, minimally invasive approach.
AB  - The purpose of this study is to evaluate the effectiveness and safety of a
      computed tomography (CT)-guided, multidisciplinary, minimally invasive approach
      to the treatment of patients with large, refractory malignant fibrous
      histiocytoma. This approach includes microwave ablation and absolute alcohol
      therapy combined with 125I seed implantation. Seven patients (5 males and 2
      females, 26-78 years old, mean 49.7 years old) with large, refractory malignant
      fibrous histiocytoma participated in this study. The tumors had an average
      maximum diameter of 14.1 cm (10.0-19.0 cm). Follow-up was conducted for an
      average of 35.7 months to determine the local control rate, overall survival
      rate, and clinical complications. Follow-up times ranged from 2 to 45 months.
      Pain was significantly relieved in patients treated with multidisciplinary,
      minimally invasive approach. Complete response was achieved in 5 patients
      (71.4%), partial response in the other 2 patients (28.6%). The response rate of
      this treatment was 100%. The median survival time was 35.7 months. All patients
      were alive in 2 years after the treatment. Five patients were still alive after 3
      years. The 3 year survival rate was 71.4%. The long-term complications included
      hyperpigmentation at the operative sites (n = 5) and insensible feeling at the
      ablation sites (n = 3).This CT-guided multidisciplinary, minimally invasive
      approach is an effective, safe, and feasible means of treating large, refractory
      malignant fibrous histiocytoma with minimal damage and few complications, but
      large-scale randomized clinical trials are necessary to confirm this assessment. 

PMID- 24325133
TI  - Assessment of three-dimensional set-up errors using megavoltage computed
      tomography (MVCT) during image-guided intensity-modulated radiation therapy
      (IMRT) for craniospinal irradiation (CSI) on helical tomotherapy (HT).
AB  - The purpose of this study was to assess three-dimensional (3D) set-up errors
      using megavoltage computed tomography (MVCT) during image-guided intensity
      modulated radiation therapy (IMRT) for supine craniospinal irradiation (CSI) on
      helical tomotherapy (HT). Patients were immobilized in a customized 4-clamp
      thermoplastic head mask with or without whole-body vacuum cradle. Set-up was
      based primarily on a set of cranial fiducial markers. MVCT scans were acquired
      and co-registered with planning scan separately at three different levels (brain,
      upper, and lower spine) at every fraction. Only translational displacements were
      analysed, wherein positive sign denotes deviation in anterior, left, and superior
      direction; while negative sign denotes deviation in posterior, right, and
      inferior direction. Mean displacements, systematic, and random errors of the
      study population were calculated at all three levels separately. Local residual
      uncertainty of the upper and lower spine was also derived assuming perfect co
      registration of the skull. Set-up margins for clinical target volume (CTV) to
      planning target volume (PTV) were derived at these three levels separately using
      published margin recipes. Data from 1868 co-registrations in 674 fractions on 33
      patients was included. The mean displacements in the lateral, longitudinal, and
      vertical directions were -1.21, -1.36, and 1.38 mm; -1.25, -0.34, and 0.65 mm;
      and -1.47, -2.78, and 0.22 mm for the brain; upper spine; and lumbar spine
      respectively. The corresponding 3D vector of displacement was 2.28; 1.45; and
      3.15 mm respectively. There was a distinct systematic trend towards increasing
      inaccuracy from the brain towards the lower spine. Using Stroom's formula, the
      minimum recommended CTV to PTV margins in absence of daily image-guidance were
      6.5; 7.0; and 9.5 mm for the brain; upper spine; and lower spine respectively.
      This increased to 7.5; 8.5; and 11.5 mm using van Herk's formula. Subset and
      sensitivity analyses could not identify any factor predictive of increased
      inaccuracy. Residual uncertainty of the spinal column was lesser after daily co
      registration referenced to the skull, suggesting that smaller set-up margins
      maybe appropriate while using daily image-guidance with an online correction
      protocol. Daily MVCT imaging during supine CSI on HT provides volumetric
      verification of the set-up process. There is substantial site-dependent
      variability in translational displacements that increases systematically from
      brain towards the lower spine with implications for differential set-up -margins
      for the brain, upper, and lower spine. 

PMID- 24325134
TI  - Biological effects of passive versus active scanning proton beams on human lung
      epithelial cells.
AB  - The goal was to characterize differences in cell response after exposure to
      active beam scanning (ABS) protons compared to a passive delivery system. Human
      lung epithelial (HLE) cells were evaluated at various locations along the proton
      depth dose profile. The dose delivered at the Bragg peak position was essentially
      identical (~4 Gy) with the two techniques, but depth dose data showed that ABS
      resulted in lower doses at entry and more rapid drop-off after the peak. Average
      dose rates for the passive and ABS beams were 1.1 Gy/min and 5.1 Gy/min,
      respectively; instantaneous dose rates were 19.2 Gy/min and 2,300 Gy/min (to a
      0.5 * 0.5 mm(2) voxel). Analysis of DNA synthesis was based on (3)H-TdR
      incorporation. Quantitative real-time polymerase chain reaction (RT-PCR) was done
      to determine expression of genes related to p53 signaling and DNA damage; a total
      of 152 genes were assessed. Spectral karyotyping and analyses of the Golgi
      apparatus and cytokines produced by the HLE cells were also performed. At or near
      the Bragg peak position, ABS protons resulted in a greater decrease in DNA
      synthesis compared to passively delivered protons. Genes with >2-fold change (P <
      0.05 vs. 0 Gy) after passive proton irradiation at one or more locations within
      the Bragg curve were BTG2, CDKN1A, IFNB1 and SIAH1. In contrast, many more genes
      had >2-fold difference with ABS protons: BRCA1, BRCA2, CDC25A, CDC25C, CCNB2,
      CDK1, DMC1, DNMT1, E2F1, EXO1, FEN1, GADD45A, GTSE1, IL-6, JUN, KRAS, MDM4, PRC1,
      PTTG1, RAD51, RPA1, TNF, WT1, XRCC2, XRCC3 and XRCC6BP1. Spectral karyotyping
      revealed numerous differences in chromosomal abnormalities between the two
      delivery systems, especially at or near the Bragg peak. Percentage of cells
      staining for the Golgi apparatus was low after exposure to passive and active
      proton beams. Studies such as this are needed to ensure patient safety and make
      modifications in ABS delivery, if necessary. 

PMID- 24325135
TI  - Optimized PET imaging for 4D treatment planning in radiotherapy: the virtual 4D
      PET strategy.
AB  - The purpose of the study is to evaluate the performance of a novel strategy,
      referred to as "virtual 4D PET", aiming at the optimization of hybrid 4D CT-PET
      scan for radiotherapy treatment planning. The virtual 4D PET strategy applies 4D
      CT motion modeling to avoid time-resolved PET image acquisition. This leads to a
      reduction of radioactive tracer administered to the patient and to a total
      acquisition time comparable to free-breathing PET studies. The proposed method
      exploits a motion model derived from 4D CT, which is applied to the free
      breathing PET to recover respiratory motion and motion blur. The free-breathing
      PET is warped according to the motion model, in order to generate the virtual 4D
      PET. The virtual 4D PET strategy was tested on images obtained from a 4D
      computational anthropomorphic phantom. The performance was compared to
      conventional motion compensated 4D PET. Tests were also carried out on clinical
      4D CT-PET scans coming from seven lung and liver cancer patients. The virtual 4D
      PET strategy was able to recover lesion motion, with comparable performance with
      respect to the motion compensated 4D PET. The compensation of the activity
      blurring due to motion was successfully achieved in terms of spill out removal.
      Specific limitations were highlighted in terms of partial volume compensation.
      Results on clinical 4D CT-PET scans confirmed the efficacy in 4D PET count
      statistics optimization, as equal to the free-breathing PET, and recovery of
      lesion motion. Compared to conventional motion compensation strategies that
      explicitly require 4D PET imaging, the virtual 4D PET strategy reduces clinical
      workload and computational costs, resulting in significant advantages for
      radiotherapy treatment planning. 

PMID- 24325136
TI  - Analysis of dose distribution and risk of pneumonitis in stereotactic body
      radiation therapy for centrally located lung tumors: a comparison of robotic
      radiosurgery, helical tomotherapy and volumetric modulated arc therapy.
AB  - Stereotactic body radiation therapy (SBRT) to central lung tumors is associated
      with normal -tissue toxicity. Highly conformal technologies may reduce the risk
      of complications. This study compares physical dose characteristics and
      anticipated risks of radiation pneumonitis (RP) among three SBRT modalities:
      robotic radiosurgery (RR), helical tomotherapy (HT) and volumetric modulated arc
      therapy (VMAT). Nine patients with central lung tumors <=5 cm were compared. RR,
      HT and VMAT plans were developed per RTOG 0831. Dosimetric comparisons included
      target coverage, conformity index, heterogeneity index, gradient index, maximal
      dose at 2 cm from target (D2 cm), and dose-volume parameters for organs at risk
      (OARs). Efficiency endpoints included total beam-on time and monitor units. RP
      risk was derived from Lyman-Kutcher-Burman modeling on in-house software. The
      average GTV and PTV were 11.6 +/- 7.86 cm(3) and 36.8 +/- 18.1 cm(3). All
      techniques resulted in similar target coverage (p = 0.64) and dose conformity (p
      = 0.88). While RR had sharper fall-off gradient (p = 0.002) and lower D2 cm (p =
      0.02), HT and VMAT produced greater homogeneity (p < 0.001) and delivery
      efficiency (p = 0.001). RP risk predicted from whole or contralateral lung
      volumes was less than 10%, but was 2-3 times higher using ipsilateral volumes.
      Using whole (p = 0.04, p = 0.02) or ipsilateral (p = 0.004, p = 0.0008) volumes,
      RR and VMAT had a lower risk of RP than HT. Using contralateral volumes, RR had
      the lowest RP risk (p = 0.0002, p = 0.0003 versus HT, VMAT). RR, HT and VMAT were
      able to provide clinically acceptable plans following the guidelines provided by
      RTOG 0813. All techniques provided similar coverage and conformity. RR seemed to
      produce a lower RP risk for a scenario of small PTV-OAR overlap and small PTV.
      VMAT and HT produced greater homogeneity, potentially desirable for a large PTV
      OAR overlap. VMAT probably yields the lowest RP risk for a large PTV.
      Understanding subtle differences among these technologies may assist in
      situations where multiple choices of modality are available. 

PMID- 24325137
TI  - Image-guided Percutaneous Ablation of Small Breast Cancer: Which Technique is
      Leading the Pack?

PMID- 24325138
TI  - Spatial and temporal control of the diazonium modification of sp2 carbon
      surfaces.
AB  - Interest in the controlled chemical functionalization of sp(2) carbon materials
      using diazonium compounds has been recently reignited, particularly as a means to
      generate a band gap in graphene. We demonstrate local diazonium modification of
      pristine sp(2) carbon surfaces, with high control, at the micrometer scale
      through the use of scanning electrochemical cell microscopy (SECCM).
      Electrochemically driven diazonium patterning is investigated at a range of
      driving forces, coupled with surface analysis using atomic force microscopy (AFM)
      and Raman spectroscopy. We highlight how the film density, level of sp(2)/sp(3)
      rehybridization and the extent of multilayer formation can be controlled, paving
      the way for the use of localized electrochemistry as a route to controlled
      diazonium modification. 

PMID- 24325139
TI  - Chronic subdural haematoma: How can we improve patient care and outcomes?

PMID- 24325140
TI  - Comment on: proposal for a prospective multi-centre audit of chronic subdural
      haematoma management in the United Kingdom and Ireland.

PMID- 24325141
TI  - Epidemiologic study links induction and augmentation of labor to diagnosis of
      autism.

PMID- 24325142
TI  - Using humour as an extrinsic source of emotion regulation in young and older
      adults.
AB  - It has been suggested that intrinsic abilities for regulating emotions remain
      stable or improve with ageing, but, to date, no studies have examined age-related
      differences in extrinsic emotion regulation. Since humour has been found to be an
      effective form of emotion regulation, we used a paradigm similar to that of
      Strick and colleagues (2009) with two objectives: to compare extrinsic humorous
      emotion regulation in young and older adults and to test whether the potential
      beneficial effect of humour on negative emotion is better explained by the
      cognitive distraction hypothesis or by the positive affect elicitation
      hypothesis. To this end, neutral, moderately, and strongly negative pictures
      followed by humorous, simply positive, or weird cartoons, controlled for both
      their funniness and cognitive demands, were presented to 26 young and 25 older
      adults with the instruction to report their negative feelings. When induced to
      feel moderately negative emotions, both young and older adults reported a lower
      negative feeling after viewing the humorous cartoons than after the other ones.
      This indicates that the extrinsic humorous emotion regulation skill remains
      stable with ageing and suggests that the beneficial effect of humour on emotional
      feeling cannot be seen as a purely cognitive distraction.

PMID- 24325143
TI  - Effect of hydroxychloroquine on antiphospholipid antibody-induced changes in
      first trimester trophoblast function.
AB  - PROBLEM: Women with antiphospholipid syndrome (APS) are at risk for pregnancy
      complications. Antiphospholipid antibodies (aPL) alter trophoblast function by
      triggering an inflammatory cytokine response; modulating angiogenic factor
      secretion; and inhibiting migration. While patients with APS are often treated
      with hydroxychloroquine (HCQ), its effect on trophoblast function is poorly
      understood. METHOD OF STUDY: A human first trimester trophoblast cell line was
      treated with or without antihuman beta2GPI mAbs in the presence or absence of
      HCQ. Supernatants were analyzed by ELISA. Cell migration was measured using a
      colormetric assay. RESULTS: Antiphospholipid antibodies-induced trophoblast IL-8,
      IL-1 beta, PlGF, and sEndoglin secretion were not altered by HCQ. aPL-induced
      inhibition of trophoblast migration was partially reversed by HCQ, even though
      HCQ significantly increased secretion of pro-migratory IL-6 to greater than
      baseline. aPL-induced upregulation of TIMP2 appears to inhibit trophoblast
      migration; the inability of HCQ to prevent aPL-induced TIMP2 may explain why
      migration was only partially restored. CONCLUSION: Hydroxychloroquine reversed
      the aPL-inhibition of trophoblast IL-6 secretion and partially limited aPL
      inhibition of cell migration. Thus, some form of combination therapy that
      includes HCQ may be beneficial to pregnant APS patients.

PMID- 24325144
TI  - Cultural capital and attitudes toward homosexuals: exploring the relation between
      lifestyles and homonegativity.
AB  - This article explores the potential of cultural capital as explanatory factor in
      understanding homonegativity. Building on recent findings suggesting the need for
      a cultural component in understanding homonegativity, this article explores the
      relation between lifestyles (the measurable expression of cultural capital) and
      homonegativity. Using the "Social-Cultural Changes in Flanders 2006" survey (a
      population-wide survey in Flanders, the northern part of Belgium), we observed
      that homonegativity is lowest in lifestyle clusters where cultural capital is
      higher. This effect, furthermore, is maintained even after controlling for other
      homonegativity correlates. These results suggest that cultural capital, expressed
      by lifestyles, is a valuable addition to the understanding of homonegativity. 

PMID- 24325145
TI  - On the Coyne and Orr-igin of species: effects of intrinsic postzygotic isolation,
      ecological differentiation, x chromosome size, and sympatry on Drosophila
      speciation.
AB  - Coyne and Orr found that mating discrimination (premating isolation) evolves much
      faster between sympatric than allopatric Drosophila species pairs. Their meta
      analyses established that this pattern, expected under reinforcement, is common
      and that Haldane's rule is ubiquitous in Drosophila species divergence. We
      examine three possible contributors to the reinforcement pattern: intrinsic
      postzygotic isolation, dichotomized as to whether hybrid males show complete
      inviability/sterility; host-plant divergence, as a surrogate for extrinsic
      postzygotic isolation; and X chromosome size, whether roughly 20% or 40% of the
      genome is X-linked. We focus on "young" species pairs with overlapping ranges,
      contrasted with allopatric pairs. Using alternative criteria for "sympatry" and
      tests that compare either level of prezygotic isolation in sympatry or frequency
      of sympatry, we find no statistically significant effects associated with X
      chromosome size or our coarse quantifications of intrinsic postzygotic isolation
      or ecological differentiation. Although sympatric speciation seems very rare in
      animals, the pervasiveness of the reinforcement pattern and the commonness of
      range overlap for close relatives indicate that speciation in Drosophila is often
      not purely allopatric. It remains to determine whether increased premating
      isolation with sympatry results from secondary contact versus parapatric
      speciation and what drives this pattern. 

PMID- 24325146
TI  - Family voice with informed choice: coordinating wraparound with research-based
      treatment for children and adolescents.
AB  - The wraparound process is a type of individualized, team-based care coordination
      that has become central to many state and system efforts to reform children's
      mental health service delivery for youths with the most complex needs and their
      families. Although the emerging wraparound research base is generally positive
      regarding placements and costs, effect sizes are smaller for clinical and
      functional outcomes. This article presents a review of literature on care
      coordination and wraparound models, with a focus on theory and research that
      indicates the need to better connect wraparound-enrolled children and adolescents
      to evidence-based treatment (EBT). The article goes on to describe how recently
      developed applications of EBT that are based on quality improvement and flexible
      application of "common elements" of research-based care may provide a more
      individualized approach that better aligns with the philosophy and procedures of
      the wraparound process. Finally, this article presents preliminary studies that
      show the feasibility and potential effectiveness of coordinating wraparound with
      the Managing and Adapting Practice system, and discusses intervention development
      and research options that are currently under way. 

PMID- 24325147
TI  - Efficacy of simethicone and N-acetylcysteine as premedication in improving
      visibility during upper endoscopy.
AB  - BACKGROUND: Simethicone and N-acetylcysteine have been widely used in improving
      endoscopic visibility. However, the optimal dose, volume, and dosing time for the
      premedication regimen are still unclear. AIM: Our aim was to assess the efficacy
      of premedication in improving endoscopic visibility and determine the
      contributions of dose, volume, and premedication time. METHODS: A total of 1849
      patients were prospectively treated in three groups: group A: 100-mg simethicone
      suspension in 5 mL water; group B: 100-mg simethicone suspension in 100 mL water;
      and group C: 100-mg simethicone suspension in 100 mL water containing 200 mg N
      acetylcysteine. Mucosa visibility was assessed at seven sites of upper
      gastrointestinal tract. The sum of scores was considered as total mucosal
      visibility score (TMVS). RESULTS: The upper body of stomach had the worst
      visibility score for all groups. TMVS of groups B and C were significantly lower
      than those of group A. Group C had a significantly fewer patients requiring
      endoscopic flushing than groups A and B. The TMVS for groups B and C were
      significantly lower than for group A within 30 min of beginning premedication.
      Beyond 30 min of premedication, there was no significant difference in the TMVS
      among groups. CONCLUSIONS: Premedication using 100 mg simethicone in 100 mL of
      water improves endoscopic visibility. Addition of N-acetylcysteine to simethicone
      in 100 mL of water reduces the need for endoscopic flushing. For patients unable
      to tolerate a large fluid volume, a 5-mL simethicone suspension administered more
      than 30 min prior to upper endoscopy is suggested.

PMID- 24325148
TI  - Lymph node harvest in single incision laparoscopic surgery for colorectal
      malignancy.
AB  - AIM: Single incision laparoscopic surgery (SILS) has not been sufficiently
      evaluated with respect to its oncological equivalence to conventional
      laparoscopic or open surgery. METHOD: Of 507 patients who had SILS for colorectal
      diseases in our institution, 87 had segmental resection for colorectal
      adenocarcinoma. For each of the surgical specimens the number of lymph nodes
      which can be expected to be identified by the pathologist was calculated using
      the ACPGBI lymph node harvest model, which was developed from a nationwide
      database of 5845 surgical specimens. The predicted number of lymph nodes was
      compared with the number identified in our SILS specimens. RESULTS: The median
      predicted number of lymph nodes was 11 (4.5-14.8) compared with 18 (5-44) in the
      SILS specimens (P < 0.001). In all subgroups analysed for various operations, the
      lymph node harvest in the SILS specimens was significantly higher than predicted.
      CONCLUSION: In terms of lymph node harvest SILS seems to be comparable to
      conventional open or laparoscopic surgery.

PMID- 24325149
TI  - Ultrasonographic characterization of follicle deviation in follicular waves with
      single dominant and codominant follicles in dromedary camels (Camelus
      dromedarius).
AB  - Follicular wave emergence was synchronized by treating camels with GnRH when a
      dominant follicle (DF) was present in the ovaries. Animals were scanned twice a
      day from day 0 (day of GnRH treatment) to day 10, to characterize emergence and
      deviation of follicles during the development of the follicular wave. Follicle
      deviation in individual animals was determined by graphical method. Single DFs
      were found in 16, double DFs in 9 and triple DFs in two camels. The incidence of
      codominant (double and triple DFs) follicles was 41%. The interval from GnRH
      treatment to wave emergence, wave emergence to deviation, diameter and growth
      rate of F1 follicle before or after deviation did not differ between the animals
      with single and double DFs. The size difference between future DF(s) and the
      largest subordinate follicle (SF) was apparent from the day of wave emergence in
      single and double DFs. Overall, interval from GnRH treatment to wave emergence
      and wave emergence to the beginning of follicle deviation was 70.6 +/- 1.4 and
      58.6 +/- 2.7 h, respectively. Mean size of the DF and largest SF at the beginning
      of deviation was 7.4 +/- 0.2 and 6.3 +/- 0.1 mm, respectively. In conclusion, the
      characteristics of follicle deviation are similar between the animals that
      developed single or double DFs.

PMID- 24325150
TI  - What do paediatric trainees require from their clinical supervisors?
AB  - AIM: Clinical supervisors are appointed to ensure that medical trainees receive a
      satisfactory education, improve their academic orientation and develop
      professional attitudes. The aim of this study was to find out, from the
      paediatric trainee's perspective, how their clinical supervisor could best do
      that. METHODS: We conducted in-depth interviews with seven paediatric trainees in
      a university hospital. A template analysis of the transcribed data explored what
      trainees expect from their clinical supervisors and what they would change if
      they could. RESULTS: Trainees wanted the supervision process to begin with
      negotiating how their supervisory relationship would be structured and how the
      time could be used to best effect. They wanted their supervisors to provide them
      with stimulating, multifaceted guidance and encouragement and support a
      reflective approach that linked theory with practice. CONCLUSION: Trainees wanted
      their supervisors to support them as they took a reflective approach to their
      practical work and to help them to bridge theoretical and applied learning.

PMID- 24325151
TI  - Community stigma endorsement and voluntary counseling and testing behavior and
      attitudes among female heads of household in Zambezia Province, Mozambique.
AB  - BACKGROUND: Some aspects of HIV-related stigma have been shown to be a barrier to
      HIV services uptake and adherence to antiretroviral treatment (ART).
      Distinguishing which domains of stigma impact HIV services uptake can enhance the
      efficacy and efficiency of stigma-reduction interventions. METHODS: The
      relationships between use of voluntary counseling and testing (VCT) services and
      two domains of community stigma identified through factor analysis, negative
      labeling/devaluation and social exclusion, were investigated among 3749 female
      heads of household. Data were from a general household survey conducted in rural
      Mozambique. Multivariable logistic regression outcomes were: lifetime VCT use,
      past-6-months VCT use and VCT endorsement. RESULTS: Thirteen percent (13%) of the
      participants reported lifetime VCT use, 10% reported past-6-months VCT use and
      63% endorsed VCT. A 25-point decrease (from 50 to 25) in the score for negative
      labeling and devaluation stigma was associated with increased lifetime VCT use
      (adjusted OR: 1.6, 95% CI: 1.1-2.3) and past-6-months VCT use (adjusted OR: 1.6,
      95% CI: 1.1-2.4). A decrease from 50 to 25-points in the score for social
      exclusion stigma was associated with 1.5 and 1.3-fold increase in odds for past-6
      months VCT use and endorsing VCT use, respectively (p < 0.001 for both). Compared
      with never-testers, considerably high endorsement of VCT use was observed among
      testers who did not receive HIV test results (adjusted OR: 2.7, 95% CI: 1.6-4.6)
      and much higher among testers who received results (adjusted OR: 7.3, 95% CI: 4.9
      11.0). Distance from health facilities was associated with lower VCT use, but not
      lower endorsement of VCT. CONCLUSIONS: VCT use and endorsement might differ by
      domains of stigma held by individuals in the community. Greater uptake and
      favorable disposition towards use of VCT services in rural settings might be
      achieved by addressing stigma via domain-specific interventions and by improving
      the proximity of services and the dissemination of HIV test results.

PMID- 24325153
TI  - Parent experiences of inpatient pediatric care in relation to health care
      delivery and sociodemographic characteristics: results of a Norwegian national
      survey.
AB  - BACKGROUND: The national survey of parent experiences with inpatient pediatric
      care contribute to the Norwegian system of health care quality indicators. This
      article reports on the statistical association between parent experiences of
      inpatient pediatric care and aspects of health care delivery, child health status
      and health outcome as assessed by the parents, and the parents' sociodemographic
      characteristics. METHODS: 6,160 parents of children who were inpatients at one of
      Norway's 20 pediatric departments in 2005 were contacted to take part in a survey
      that included the Parent Experience of Pediatric Care questionnaire. It includes
      25 items that form six scales measuring parent experiences: doctor services,
      hospital facilities, information discharge, information about examinations and
      tests, nursing services and organization. The six scales were analyzed using OLS
      regression. RESULTS: 3,308 (53.8%) responded. Mean scores ranged from 62.81
      (organization) to 72.80 (hospital facilities) on a 0-100 scale where 100 is the
      best possible experience. Disappointment with staff, unexpected waiting,
      information regarding new medication, whether the staff were successful in easing
      the child's pain, incorrect treatment and number of previous admissions had a
      statistically significant association with at least five of the PEPC scale
      scores. Disappointment with staff had the strongest association. Most
      sociodemographic characteristics had weak or no associations with parent
      experiences. CONCLUSIONS: The complete relief of the child's pain, reducing
      unexpected waiting and disappointment with staff, and providing good information
      about new medication are aspects of health care that should be considered in
      initiatives designed to improve parent experiences. In the Norwegian context
      parent experiences vary little by parents' sociodemographic characteristics.

PMID- 24325152
TI  - Clinical trials in children.
AB  - Safety and efficacy data on many medicines used in children are surprisingly
      scarce. As a result children are sometimes given ineffective medicines or
      medicines with unknown harmful side effects. Better and more relevant clinical
      trials in children are needed to increase our knowledge of the effects of
      medicines and to prevent the delayed or non-use of beneficial therapies. Clinical
      trials provide reliable evidence of treatment effects by rigorous controlled
      testing of interventions on human subjects. Paediatric trials are more
      challenging to conduct than trials in adults because of the paucity of funding,
      uniqueness of children and particular ethical concerns. Although current
      regulations and initiatives are improving the scope, quantity and quality of
      trials in children, there are still deficiencies that need to be addressed to
      accelerate radically equitable access to evidence-based therapies in children. 

PMID- 24325154
TI  - Blood group discrepancies at a tertiary care centre - analysis and resolution.
AB  - INTRODUCTION: The ABO system is the most important of all blood group systems in
      transfusion practice. ABO grouping is a simple, accurate, and precise procedure
      and to be considered valid, the results of cell grouping and serum grouping
      should agree. The aim of this study was to assess the cause of discrepancies and
      its implication in transfusion practice. METHODS: This study was performed
      between January 2010 and May 2013. We analyzed ABO discrepancies which were
      detected serologically in blood donors, where a result of cell grouping and serum
      grouping was discordant. Confirmation of subgroups was carried out by adsorption
      and elution technique. Saliva of these donors was also tested for A, B, and H
      antigens by inhibition tests. RESULTS: Twenty-eight blood group discrepancies
      were observed in 44 425 blood groups tested during the study period, thus giving
      an overall frequency of 0.06%. Technical errors leading to blood group ABO
      discrepancy were noticed in five cases. Sample-related problems that affect red
      cell testing were observed in twenty cases, and the most common cause of ABO
      discrepancies in this category was subgroups of A and B. ABO discrepancies that
      affect the serum testing included the presence of additional antibodies other
      than anti-A and anti-B. CONCLUSION: It is imperative to recognize discrepant
      results and resolve them. Correct blood typing and labeling of an individual are
      essential to prevent ABO incompatibility.

PMID- 24325155
TI  - Are patients' preferences regarding the place of treatment heard and addressed at
      the point of referral: an exploratory study based on observations of GP-patient
      consultations.
AB  - BACKGROUND: Today, in several north-western European countries, patients are
      encouraged to choose, actively, a healthcare provider. However, patients often
      visit the provider that is recommended by their general practitioner (GP). The
      introduction of patient choice requires GPs to support patients to be involved,
      actively, in the choice of a healthcare provider. We aim to investigate whether
      policy on patient choice is reflected in practice, i.e. what the role of the
      patient is in their choices of healthcare providers at the point of referral and
      to what extent GPs' and patients' healthcare paths influence the role that
      patients play in the referral decision. METHODS: In 2007-2008, we videotaped
      Dutch GP-patient consultations. For this study, we selected, at random, 72
      videotaped consultations between 72 patients and 39 GPs in which the patient was
      referred to a healthcare provider. These were analysed using an observation
      protocol developed by the researchers. RESULTS: The majority of the patients had
      little or no input into the choice of a healthcare provider at the point of
      referral by their GP. Their GPs did not support them in actively choosing a
      provider and the patients often agreed with the provider that the GP proposed.
      Patients who were referred for diagnostic purposes seem to have had even less
      input into their choice of a provider than patients who were referred for
      treatment. CONCLUSIONS: We found that the GP chooses a healthcare provider on
      behalf of the patient in most consultations, even though policy on patient choice
      expects from patients that they choose, actively, a provider. On the one hand,
      this could indicate that the policy needs adjustments. On the other hand,
      adjustments may be needed to practice. For instance, GPs could help patients to
      make an active choice of provider. However, certain patients prefer to let their
      GP decide as their agent. Even then, GPs need to know patients' preferences,
      because in a principal-agent relationship, it is necessary that the agent is
      fully informed about the principal's preferences.

PMID- 24325156
TI  - [Precursors of breast cancer].
AB  - It has become apparent that estrogen receptor (ER) - positive and - negative
      breast lesions are completely distinct diseases. Precursors of low-grade breast
      cancer are low-grade premalignant lesions, usually ER and progesterone receptor
      (PR) positive and HER2 negative. On the other hand, precursors of high-grade
      breast cancer are high-grade premalignant lesions, usually ER and PR negative and
      HER2 positive. Lobular neoplasia (LN) and ductal carcinoma in situ (DCIS) are
      important from the clinical point of view. LN increases the risk of bilateral
      breast cancer. This is why the recommendation for the treatment of LN is very
      different -  from just following up up to bilateral mastectomy. The complete
      surgical excision of the lesion with negative margins is the usual treatment of
      DCIS. Several big randomized clinical trials showed the benefit of adjuvant
      radiotherapy (RT). Some of them suppose that there is a group of patients who do
      not need adjuvant treatment. The benefit of adjuvant tamoxifen is clear only for
      patients with ER positive disease. The UK/ ANZ study showed the benefit of
      tamoxifen only in patients without RT.

PMID- 24325157
TI  - [Precancerous conditions in the ENT area].
AB  - An important part of tumor prevention is early detection, dia-gnosis, treatment
      and screening of precancerous conditions. Correct detection and screening of
      premalignant lesions leads to early dia-gnosis of a malignant process which
      provides a better chance to completely cure the patient and also predicts better
      quality of life. Precancerous conditions look like whitish, red or mixed mucose
      lesions (leukoplakia, erytroplakia, erytroleukoplakia) which are visible during
      clinical examination. Nevertheless, these mucose changes are not absolutely
      conclusive. Therefore, histological testing is necessary for dia-gnosis and
      determination of bio-logical potencial of precancerous lesions. Precancerous
      lesions as a term of histological terminology means dysplasia. The risk of
      progression of dysplasia into a carcinoma depends on a grade of dysplasia. The
      conservative or surgical treatment is chosen according to localisation and grade
      of dysplasia.

PMID- 24325158
TI  - [Premalignant conditions of the esophagus].
AB  - Esophageal cancer has often poor survival when it is diagnosed at the time of
      clinical symptoms. Precancerous lesions of the esophagus are targets of interest
      in selected group of patients with important risk factors. Barrett's esophagus - 
      intestinal metaplasia is the main precursor lesion for the development of
      esophageal adenocarcinoma, the tumor with increased incidence. The major risk
      factor for Barrett's esophagus is longterm gastroesophageal reflux disease. In
      addition to antireflux therapy, the endoscopic surveillance and followup are
      scheduled in order to detect adenocarcinoma and its precursor dysplastic lesions
      at an early and curable stage. The patients with achalasia, caustic injury of the
      esophagus and those with head and neck cancer are at increased risk of
      development of the squamous cell esophageal cancer. The aim of this paper is to
      provide an overview of the risk factors, epidemiology, screening and surveillance
      of premalignant lesions of the esophagus. Recent endoscopic and surgical
      procedures to treat advanced dysplastic lesions and early cancer are discussed.

PMID- 24325159
TI  - [Precancerous conditions and lesions of the stomach].
AB  - Gastric carcinoma is a common malignant disease associated with an unfavorable
      prognosis in the case of late dia-gnosis. The most significant precancerous
      condition is chronic atrophic gastritis and intestinal metaplasia caused by
      Helicobacter pylori infection. These longlasting changes may lead to formation of
      dysplastic precancerous lesions. Upper endoscopy and histologic examination of
      forceps bio-psy specimens play a key role in the dia-gnosis of gastric
      precancerous conditions and lesions. Helicobacter pylori eradication therapy and
      endoscopic surveillance are main therapeutic modalities of gastric precancerous
      conditions. Localized precancerous lesions and early gastric neoplasia without
      the risk of lymphatic spread could be cured by means of endoscopic resection
      techniques.

PMID- 24325160
TI  - [Precancerous conditions and risk factors for pancreatic and bile duct cancer].
AB  - Pancreatic cancer has one of the worst prognoses of any type of cancer. Early
      detection and surgery is the best chance for cure. However, symptoms are
      typically vague and occur when the cancer is unresectable. Early detection
      through screening is likely to be the best hope to improve survival. The
      relatively low incidence of pancreatic cancer and the insensitive screening
      techniques currently available render this approach expensive and inefficient in
      the general population. Early detection and screening for pancreatic cancer in
      the current state should be limited to highrisk patiens. But hereditary factors
      account about 10% of patients with pancreatic cancer (familial pancreatic cancer,
      hereditary pancreatitis, Peutz Jeghers syndrom etc.). Continued efforts are
      needed to discover effective test to identify patients with nonhereditary risk
      factors who will benefit from screening and also to develop less invasive and
      more costeffective screening modalities aimed at controlling pancreatic cancer. A
      combined ap-proach of serum markers, genetic markers and specific imaging studies
      may prove to be the future of pancreatic screening.

PMID- 24325161
TI  - [Premalignant conditions of the small bowel].
AB  - Small intestinal dysplastic lesions are rare and difficult to detect before they
      progress to cancer. New investigative modalities, such as capsule endoscopy and
      doubleballoon enteroscopy, are very promising in search for premalignant lesions.
      Screening patients at high-risk for small bowel neoplasia is the only sensible
      approach. Duodenal adenoma represents the most easily accessible tumors with the
      possibility of curative endoscopic resection. Due to the strong association of
      the small bowel and colonic adenomas, it is always necessary to perform
      colonoscopy. In young patients, the exclusion of familial polyposis by genetic
      testing is always mandatory. Patients with celiac disease are especially at risk
      of developing nonHodgkins lymphomas and adenocarcinomas. There is a high-risk of
      ampuloma and other adenomas in patients with familial adenomatous polyposis.
      Patients with prolonged and complicated course of Crohns disease, Peutz Jeghers
      syndrome and patients with ileoanal pouch have higher risk of adenocarcinoma of
      the small intestine.

PMID- 24325162
TI  - [Premalignancies of colon].
AB  - The most common premalignant lesions of colorectal carcinoma include sporadic
      adenomas. Tubular and tubulovillous adenomas with mild dysplasia are considered
      benign lesions, while villous adenomas represent tumors with uncertain bio
      logical behavior. In recent years, demonstrable growth of flat lesions in the
      proximal intestine has been seen. Precision and yield of colonoscopy depends to
      some extent on good preparation, careful screening of intestine and use of new
      instruments of better quality. As an indicator of screening colonoscopy quality,
      the so -called adenoma detection rate is used. The text briefly describes options
      of endoscopic and surgical resolving of premalignancies. In the Czech Republic,
      attendance in the screening program is low, which could be changed by prepared
      addressed invitations of clients. The population with a genetic or familiar risk
      is examined according to recommended procedures intended for increased- risk
      persons.

PMID- 24325163
TI  - [Preinvasive lesions in gynecology -  vulva].
AB  - For preinvasive lesions of vulva, a common term VIN -  vulval intraepithelial
      neoplasia is used. VIN is a histological dia-gnosis based on abnormal squamous
      epithelial proliferation. There are two types of VIN apart from their association
      with human papillomavirus (HPV). Undifferentiated (usual) vulval intraepithelial
      neoplasia is commonly associated with carcinogenic genotypes of HVP, whereas
      differentiated vulval intraepithelial neoplasia is not associated with high-risk
      genotypes of HPV. The article presents an overview of VIN occurence and
      epidemiology, its classification system and dia-gnostics. In conclusion, VIN
      therapeutical possibilities are presented. It can be treated with surgical
      therapy (local excision, partial vulvectomy, vulvectomy, laser vaporization) or
      medical therapy (imiquimod).

PMID- 24325164
TI  - [Preinvasive lesions in gynaecology -  vagina].
AB  - Preinvasive lesions of the vagina are relatively rare, clearly defined
      afflictions, originating most of all in association with the highrisk human
      papillomavirus infection (HR HPV). The most frequent appearance is in coincidence
      with preinvasive lesions of uterine cervix and in vaginal cuff after
      hysterectomy. Preinvasive vaginal lesions are divided into squamous lesions
      (vaginal intraepithelial neoplasia) and nonsquamous lesions. Vaginal adenosis
      belongs to nonsquamous vaginal preinvasive lesions and is a precursor lesion of
      vaginal clear cell carcinoma. Surgical and nonsurgical techniques including laser
      destructive methods and local administration of 5- fluorouracile are used in the
      treatment of preinvasive lesions of vagina.

PMID- 24325165
TI  - [Preinvasive lesions in gynaecology - uterine cervix].
AB  - Preinvasive lesion of the uterine cervix can give rise to cervical cancer. High
      risk human papillomaviruses with high oncogenic potential are considered to be
      the main etiopathological factors with interaction of other risk factors
      (recurrent inflammation of the cervix, injury of the cervix, immunosuppressive
      conditions, sexual promiscuity, etc.). Early dia-gnosis of these changes at
      regular gynecological examinations and adequate treatment can prevent of
      malignant transformation. Organized cervical screening and implementation of
      nationwide vaccination against human papillomavirus promises to reduce the
      incidence of cervical cancer.

PMID- 24325166
TI  - [Preinvasive lesions in gynaecology -  endometrium].
AB  - Preinvasive lesions of the endometrium are histopathological and molecular
      alterations related to high-risk of uterine carcinoma development. Incidence has
      increasing tendency. Atypical endometrial hyperplasia is the preinvasive lesion
      of type I endometrial carcinoma, developing under a hyperestrogenic background.
      Carcinoma in situ of the endometrium is considered to be precursor lesion of type
      II endometrial carcinoma, first of all uterine serous carcinoma. Hysterectomy and
      bilateral oophorectomy is the main therapeutical modality in both preinvasive
      lesions of the endometrium. The hormonal therapy with progestogens is the
      possibility of fertility sparing approach in treatment of histological findings
      of atypical endometrial hyperplasia in young women. Even though preinvasive
      lesions of the endometrium are clearly defined, the possibilities of endometrial
      cancer screening are markedly limited.

PMID- 24325167
TI  - [Preinvasive lesions in gynaecology -  ovary].
AB  - In comparison to malignant tumors of vulva, vagina, cervix and uterine corpus,
      clear morphologic and molecular genetic features of precursor lesions of ovarian
      carcinoma have not been defined yet. We can see an effort to describe preinvasive
      lesions to allow dia-gnostics and treatment prior to development of invasive
      ovarian cancer. This tendency is magnified by the fact that ovarian carcinomas
      have the highest mortality from all gynecological malignancies. Currently,
      reports confirming different morphology, pathogenesis and molecular alterations
      in heterogeneous group of ovarian carcinomas have been described. There is a
      tendency to divide epithelial malignant tumors into two groups. Low grade ovarian
      serous carcinoma, low grade endometrioid, clear cell, mucinous ovarian cancers
      and Brenner tumors of ovary are categorized as type I ovarian tumors. Highgrade
      serous carcinoma, undifferentiated carcinomas and malignant mixed mesodermal
      tumors of the ovary (MMMTs) belong to type II tumors. A potential precursor
      lesion of highgrade serous ovarian cancer has been defined -  serous tubal
      intraepithelial carcinoma.

PMID- 24325168
TI  - Red blood cell phenotyping after transfusion: an in vitro model.
AB  - Recipients red blood cell (RBC) phenotyping using serologic techniques, within 3
      months of a transfusion, is considered unreliable. We conducted in vitro
      experiments to determine how long recipients RBC phenotyping results would be
      compromised. In vitro models were created to mimic in vivo posttransfusion ratios
      of "transfused" RBCs with either a single or a double dose of an antigen at 10
      day intervals from day 0 to day 90 in hypothetical recipients with varying
      weights and hematocrits (Hct) receiving varying numbers of RBC units. In general,
      a reliable recipient RBC phenotype was possible earlier after transfusion in
      larger recipients, those with higher Hct, and those transfused with fewer RBC
      unit and if the transfused units had the antigen of interest in single, rather
      than double, dose. We believe that a reliable RBC phenotype, using routine
      serologic techniques, can often be obtained well before 3 months after
      transfusion. Similar studies with other donors, antigens, antisera, and methods
      and in actual patients will be useful.

PMID- 24325169
TI  - Identifying D-positive donors using a second automated testing platform.
AB  - Because of the variability of D expression, one method may be inadequate to
      correctly classify donors with variant RHD alleles. We evaluated the use of a
      solid -phase automated platform (ImmucorGamma Galileo) to confirm D- test results
      obtained on first-time donors on the Beckman Coulter PK7300 automated microplate
      test system. Samples with discordant results were analyzed by serologic tube
      methods, RHD genotyping using the BLOODchip platform (Progenika) and, if
      necessary, sequencing. We estimated the number of cases of alloimmunization in
      women younger than 50 years likelyto be prevented by the addition of Galileo
      testing. From May 2011 to May 2012, 910,220 donor samples were tested; 15,441
      were first-time donors with concordant D- results. Five donors tested D- on the
      PK7300 and weak D+ on the Galileo; one was found to be a false positive on
      further testing. On manual testing, the other four donors had positive indirect
      antiglobulin test results with one to three of the antisera used and were C+. On
      BLOODchip testing, two donors were classified as D+, and two were assigned a "no
      call". D variants included weak D type 67, weak D type 9, and two novel variants.
      Approximately 10 percent of D- units are transfused to women younger that 50
      years. Assuming an alloimmunization rate of 30 percent, use of the Galileo would
      prevent approximately one alloimmunization every 5 to 6 years in this patient
      group. We conclude that the yield of preventing alloimmunization in this
      population by adding a second automated seologic testing platform is very low.

PMID- 24325170
TI  - Single-center comparison of gel microcolumn and solid-phase methods for antibody
      screening.
AB  - Our facility changed antibody screening methods from a gel microcolumn-based test
      (ID-Micro Typing System Gel TEst; Ortho Clinical Diagnostics, Inc., Raritan, NJ)
      to an automated solid-phase test (Galileo/Capture-R Ready Screen [I and II],
      Immucor, Inc., Norcross, GA). To determine whether detection rates for commonly
      encountered clinically significant red blood cell antibodies differed as a
      consequence of this change, preimplementation and postimplementation antibody
      identification records were retrospectively reviewed. A statistically significant
      difference in the percentage of positive screening tests during the gel
      microcolumn testing period (73,903 total screens, 1.56% confirmed positive)
      versus the solid0-phase screening period (80,242 total screens, 1.81% confirmed
      positive; p< 0.0002) was observed . The number of antibodies to K identified was
      significantly lower with solid phase that with gel (27% decrease; p=0.004). It is
      unknown whether there is a statistical difference in delayed or hemolytic
      transfusion reaction rates as this was not evaluated.

PMID- 24325171
TI  - Comparison of estimation of volume of fetomaternal hemorrhage using Kleihauer
      Betke test and microcolumn gel method in D-negative nonisoimmunized mothers.
AB  - In this study we assessed the efficay of the microcolumn gel method in the
      detection and quantification of the volume of fetomaternal hemorrhage (FMH) in
      comparison with the Kleihauer-Betke test (KB) in nonisoimmunized D- mothers. We
      collected blood samples from 80 D- indirect antiglobulin test-negative mothers
      over a span of more than 1 year. FMH was determined by KB and microcolumn gel
      method, and the results were compared. FMH was recorded as less than 4 mL by KB
      if no fetal cells were seen after examining 25 fields using 10x objective. If
      fetal cells were seen, slides were examined furhter to quantify FMH. By
      microcolumn gel method, FMH was reported as less than 0.1 percent, 0.1 percent,
      0.2 percent, and 0.4 percent or greater. None of the patients had FMH greater
      than 15 mL by KB . Sixty-two patients (77.5%) had FMH less than 4mL by KB. In all
      these cases , FMH was less than or equal 0.2 percent (approximately 4mL) by
      microcolumn gel method. The mean volume of FMH in the remaining 18 (22.5%) cases
      by KB was 8.3 +/- 1.7 mL. Fifteen (83.3%) of these 18 cases had FMH of at least
      0.4 percent (approximately 8 mL) by gel technology. Three cases (16.7%) that
      differed from KB results had FMH of 0.2 percent by microcolumn gel method with a
      maximal FMH of 6.4 mL by KB. FMH was significanlty increased in cesarean delivery
      (mean FMH 9.5 +/- 0.8 mL, range 7.9-10.4 mL, p=0.001) abd abtepartum hemorrahge
      (mean FMH 9.5 +/- 0.9 mL, range 7.9-10.4 mL, p< 0.001). Microcolumn gel method is
      an effective screening test . Technologies like KB and flow cytometry are better
      options for detecting a large volume of FMh. Antepartum hemorrhage and cesarean
      delivery are risk factors for FMH. the 300-ug dose of cases. We need to analyze
      the relative cost-effectiveness of universal administration of 300ug of Rh immune
      globulin vs. FMH quantitation with subsequent administration of titrated doses.

PMID- 24325172
TI  - Immunosuppressive protocols for transplantation and certain hematologic
      malignancies can prevent the primary immune response to the D blood group
      antigen.
AB  - A review of the published literature on Rh alloimmunization reveals that its
      incidence varies with the volume of infused D+ red blood cells (RBCs), the
      probable Rh genotype of the RBCs, and the immune competency of the D- recipient.
      Among the reports of Rh alloimmunization on different clinical circumstances, we
      identified five studies in which a combined total of 62 D- recipients of
      hematopoetic stem cell or solid -organ transplants were transfised with D+ RBCs
      and none (0%) formed anti-D. The observation that immunosuppressive protocols
      developed to prevent rejection of tissue and organ transplants also prevented
      alloimmunization to the D blood group antigen raises the possibility of practical
      applications in blood transfusion practice.

PMID- 24325173
TI  - Trends in adult current asthma prevalence and contributing risk factors in the
      United States by state: 2000-2009.
AB  - BACKGROUND: Current asthma prevalence among adults in the United States has
      reached historically high levels. Although national-level estimates indicate that
      asthma prevalence among adults increased by 33% from 2000 to 2009, state-specific
      temporal trends of current asthma prevalence and their contributing risk factors
      have not been explored. METHODS: We used 2000-2009 Behavioral Risk Factor
      Surveillance System data from all 50 states and the District of Columbia (D.C.)
      to estimate state-specific current asthma prevalence by 2-year periods (2000
      2001, 2002-2003, 2004-2005, 2006-2007, 2008-2009). We fitted a series of four
      logistic-regression models for each state to evaluate whether there was a
      statistically significant linear change in the current asthma prevalence over
      time, accounting for sociodemographic factors, smoking status, and weight status
      (using body mass index as the indicator). RESULTS: During 2000-2009, current
      asthma prevalence increased in all 50 states and D.C., with significant increases
      in 46/50 (92%) states and D.C. After accounting for weight status in the model
      series with sociodemographic factors, and smoking status, 10 states (AR, AZ, IA,
      IL, KS, ME, MT, UT, WV, and WY) that had previously shown a significant increase
      did not show a significant increase in current asthma prevalence. CONCLUSIONS:
      There was a significant increasing trend in state-specific current asthma
      prevalence among adults from 2000 to 2009 in most states in the United States.
      Obesity prevalence appears to contribute to increased current asthma prevalence
      in some states.

PMID- 24325174
TI  - Validation of intraluminal and intraperitoneal microdialysis in ischemic small
      intestine.
AB  - BACKGROUND: We sought to define the sensitivity and specificity of
      intraperitoneal (IP) and intraluminal (IL) microdialysate metabolites in
      depicting ex vivo small intestinal total ischemia during GI-tract surgery. We
      hypothesized that IL as opposed to IP microdialysis detects small intestinal
      ischemia with higher sensitivity and specificity. METHODS: IL and IP
      microdialysate lactate, pyruvate, glucose and glycerol were analysed from small
      intestine of pancreaticoduodenectomy patients before and after occluding the
      mesenteric vasculature and routine resection of a segment of small intestine. Ex
      vivo time sequences of microdialysate metabolites were described and ROC analyses
      after 0-30, 31-60, 61-90 and 91-120 minutes after the onset ischemia were
      calculated. RESULTS: IL lactate to pyruvate ratio (L/P ratio) indicated ischemia
      after 31-60 minutes with 0.954 ROC AUC (threshold: 109) in contrast to IP L/P
      (ROC AUC of 0.938 after 61-90 minutes, threshold: 18). At 31-60 minutes IL
      glycerol concentration indicated ischemia with 0.903 ROC AUCs (thresholds: 69
      MUmol/l). IP glycerol was only moderately indicative for ischemia after 91-120
      minutes with 0,791 ROC AUCs (threshold 122 MUmol/l). After 31-60 minutes IL and
      IP lactate to glucose ratios (L/G ratio) indicated ischemia with 0.956 and 0,942
      ROC AUCs (thresholds: 48,9 and 0.95), respectively. CONCLUSIONS: The results
      support the hypothesis that intraluminal application of microdialysis and
      metabolic parameters from the small intestinal lumen indicate onset of ischemia
      earlier than intraperioneal microdialysis with higher sensitivity and
      specificity.

PMID- 24325175
TI  - Poly(4-hydroxybutyrate) (P4HB) production in recombinant Escherichia coli: P4HB
      synthesis is uncoupled with cell growth.
AB  - BACKGROUND: Poly(4-hydroxybutyrate) (P4HB), belonging to the family of bacterial
      polyhydroxyalkanoates (PHAs), is a strong, flexible and absorbable material which
      has a large variety of medical applications like tissue engineering and drug
      delivery. For efficient production of P4HB recombinant Escherichia coli has been
      employed. It was previously found that the P4HB synthesis is co-related with the
      cell growth. In this study, we aimed to investigate the physiology of P4HB
      synthesis, and to reduce the total production cost by using cheap and widely
      available xylose as the growth substrate and sodium 4-hydroxybutyrate (Na-4HB) as
      the precursor for P4HB synthesis. RESULTS: Six different E. coli strains which
      are able to utilize xylose as carbon source were compared for their ability to
      accumulate P4HB. E. coli JM109 was found to be the best strain regarding the
      specific growth rate and the P4HB content. The effect of growth conditions such
      as temperature and physiological stage of Na-4HB addition on P4HB synthesis was
      also studied in E. coli JM109 recombinant in batch culture. Under the tested
      conditions, a cellular P4HB content in the range of 58 to 70% (w w(-1)) and P4HB
      concentrations in the range of 2.76 to 4.33 g L(-1) were obtained with a
      conversion yield (Y(P4HB/Na-4HB)) of 92% w w(-1) in single stage batch cultures.
      Interestingly, three phases were identified during P4HB production: the "growth
      phase", in which the cells grew exponentially, the "accumulation phase", in which
      the exponential cell growth stopped while P4HB was accumulated exponentially, and
      the "stagnation phase", in which the P4HB accumulation stopped and the total
      biomass remained constant. CONCLUSIONS: P4HB synthesis was found to be separated
      from the cell growth, i.e. P4HB synthesis mainly took place after the end of the
      exponential cell growth. High conversion rate and P4HB contents from xylose and
      precursor were achieved here by simple batch culture, which was only possible
      previously through fed-batch high cell density cultures with glucose.

PMID- 24325177
TI  - Elevated PAPP-A sets alarm bells ringing in patients with cardiac chest pain.
AB  - Novel biochemical markers may improve the estimation of overall risk in subjects
      at a high risk of adverse cardiac events. Measurement of some of these markers,
      including pregnancy-associated plasma protein A (PAPP-A), brings significant
      prognostic information independent of traditional risk factors. PAPP-A has been
      recently identified as a marker of plaque destabilization with growing interest
      in cardiovascular research. Our group has recently demonstrated that higher
      levels of serum PAPP-A were independently associated with an increased short-term
      risk of cardiovascular events in a large sample of 2568 consecutive patients
      presenting with cardiac chest pain. PAPP-A levels above 34.6 mIU/l in cardiac
      chest-pain patients sets alarm bells ringing as a warning for higher risk of
      short-term cardiovascular adverse events, including stent thrombosis, myocardial
      infarction, ischemic stroke or cardiovascular-related death within 90 days, the
      combined primary end point of this study. Cardiac chest pain patients with PAPP-A
      levels above 34.6 mIU/l may suffer from adverse cardiovascular events five times
      more frequently within 90 days than those with lower PAPP-A levels (hazard ratio:
      5.28; 95% CI: 3.81-7.31). However, current data do not support the diagnostic
      role of PAPP-A for acute coronary syndrome in comparison to the gold standard
      biomarker troponin. Additionally, PAPP-A is known to interact with heparin, which
      may diminish its potential utility in every day clinical life. Future multicenter
      and large-volume studies are warranted to validate the use of PAPP-A in routine
      clinical practice. 

PMID- 24325178
TI  - Queer blindfolding: a case study on difference "blindness" toward persons who
      identify as lesbian, gay, bisexual, and transgender.
AB  - The purpose of this article is to introduce and explore the narrative strategy of
      queer blindfolding. Utilizing psycho-discursive qualitative methodology, the
      authors will draw from a case study to demonstrate how some beneficent, well
      intended persons who identify as heterosexual adopt the narrative strategy of
      queer blindfolding as they negotiate the discourse of heteronormativity. We will
      map this narrative strategy, compare and contrast it to racial colorblindness,
      and unpack the accompanying intra-psychic conflict and defense mechanisms that
      are utilized by the participant in the case study. We will also demonstrate how
      this discursive strategy positions participants within systemic heterosexism. 

PMID- 24325179
TI  - Clinical trial recruitment in rural South Carolina: a comparison of
      investigators' perceptions and potential participant eligibility.
AB  - INTRODUCTION: Participation in clinical trial (CT) research can help decrease
      health disparities in rural communities. The purpose of this study was to examine
      the perceptions of principal investigators (PIs) regarding CT participation
      barriers and recruitment efforts in rural South Carolina, USA and to assess the
      actual pool of potential CT participants in rural and urban South Carolina. The
      ultimate goal was to evaluate the fit between PIs' perceptions and the pool of
      eligible participants in rural South Carolina. METHODS: An online survey was
      conducted with 119 CT PIs from South Carolina's five main academic medical
      centers located in urban areas of the state, for a response rate of 31%.
      Secondary data analyses were also conducted using data from government health
      insurance plans, including the 2009 South Carolina Medicaid, the 2009 State
      Health Plan (SHP) data, and census data from the 2005-2009 American Community
      Survey (ACS). Both parametric and non-parametric statistics were used to analyze
      survey and secondary data. RESULTS: Principal investigators perceived greater
      recruitment barriers in rural areas than in the general population. They
      indicated having difficulty finding CT participants in rural areas compared to
      the general population (t= -2.985, p=0.004). Rural residents were significantly
      more likely to be perceived as lacking knowledge and understanding about CT than
      the general public (t= -2.105, p=0.038), having significantly lower literacy than
      the general public (t= -2.058, p=0.043), lacking information about available CTs
      (t= -2.913, p=0.005), and having limited accessibility to trial sites compared to
      the general population (t= -4.380, p=0.000). Patients' insurance coverage,
      however, was not found to be a significant barrier for CT participation (t=0.418,
      p=0.677). Secondary data variables were aligned with these barriers. Data
      revealed that rural residents have slightly lower educational attainment than
      urban citizens >t=5.384, p=0.000), and more people live below poverty level in
      rural areas (23%) than in urban areas (15%) (t=4.86, p=0.000). The secondary data
      analyses also showed that the majority of rural citizens covered by the SHP and
      Medicaid are eligible for CTs. ACS data revealed that 75% of people in rural
      areas meet one or more basic eligibility requirements to participate in CTs
      compared to 83% in urban areas. CONCLUSIONS: Some important barriers hinder CT
      enrollment of rural participants, such as accessibility to trial sites, poverty,
      lack of knowledge about CTs, among others. Data suggested that insurance
      coverage, however, is not a barrier to CT participation. Although CT PIs are
      correct in considering these barriers in rural areas, there still exists a large
      pool of potentially eligible CT participants in rural South Carolina. PIs, who
      were recruited from urban academic medical centers, may therefore be perpetuating
      unhelpful rural myths about CT eligibility in rural communities. Despite their
      remote locations, rural citizens should take part in medical research. Greater
      communication between PIs and rural participants and better education of PIs on
      communication strategies are needed to enhance CT participation in rural South
      Carolina.

PMID- 24325180
TI  - Urinary neutrophil gelatinase-associated lipocalin predicts graft loss after
      acute kidney injury in kidney transplant.
AB  - OBJECTIVE: Establish the prognostic value for graft loss of urinary neutrophil
      gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1),
      interleukin-18 (uIL-18), and heat shock protein 72 (uHsp72) in kidney transplant
      recipients (KTR) with acute kidney injury (AKI). METHODS: Biomarkers were
      measured in 67 KTR with AKI caused by different entities. RESULTS: After 1 year,
      11 KTR with graft loss had higher uNGAL compared to KTR without loss (p < 0.001).
      There were no differences for uKIM-1, uIL-18 and uHsp-72. uNGAL >200 ng/mL had
      84% sensitivity and 86% specificity for graft loss (ROC AUC: 0.89, 95% CI: 0.81
      0.97). uNGAL may be useful to predict graft loss after AKI.

PMID- 24325182
TI  - Freud's free clinics: a tale of two continents.
AB  - Two important schools of thought began in the nineteenth century in Central
      Europe: Marxism and psychoanalysis. They had much common but there were
      significant differences. The Marxist influence on early psychoanalysts played out
      in one way in Europe and another way in the United States. Freud and his Austro
      Marxist colleagues were committed to human welfare and social justice. They
      established a network of clinics that offered psychoanalysis to patients of
      limited means. The free clinics movement did not cross the Atlantic. There was a
      cohort of Marxists in the United States who belonged to the United States
      Communist Party. They were not publicly socially committed, but this paper will
      try to show that their Marxism influenced their psychoanalytic theory, practice,
      and politics. 

PMID- 24325183
TI  - Psychoanalytic remarks on Fromm's book "Escape from freedom".

PMID- 24325184
TI  - Development and psychoanalysis: then and now-the influence of infant studies.
AB  - In this paper I review early analytic concepts of infancy and development that
      were based on top-down theories derived from adult treatment and pathological
      formations. The therapeutic approach of neutrality, abstinence, and anonymity was
      concordant with developmental hypotheses. I then present a contemporary view of
      infancy derived from bottom-up research and observation. I describe twelve
      capacities and qualities of experience that emerge during the first year of life
      and influence all later development. 

PMID- 24325185
TI  - The implications of conceptual critiques and empirical research on unconscious
      processes for psychoanalytic theory.
AB  - The paper examines the implications of conceptual critiques and empirical
      research on psychoanalytic formulations of unconscious processes. Different
      conceptions of unconscious processes and states are discussed: as markers for
      brain states, as unformulated and not-spelled-out fleeting experiences, and as
      implicit knowledge. The author notes and discusses the interpersonal and
      interactional aspects of unconscious processes in classical theory as well as in
      contemporary formulations. Representative examples of empirical research on
      unconscious processes are presented and their implications for psychoanalytic
      conceptions are examined. The author then discusses the conception of unconscious
      processes that emerges in view of conceptual critiques, empirical research
      findings, and clinical phenomena. Finally, the emphasis of both early and late
      Freudian theory on integration of various aspects of the personality rather than
      (or at least in addition to) on conscious versus unconscious is noted, and
      various ways of understanding what it means to make the unconscious conscious are
      discussed. 

PMID- 24325186
TI  - Psychoanalysis and research: some reflections and opinions.
AB  - The author argues that existing research on the outcome of psychoanalysis and the
      psychoanalytic therapies is sufficient to claim a solid basis in scientific
      evidence for psychodynamically oriented clinical work. She explores sociocultural
      trends that increase the probability that analytic therapists and academic
      researchers will misunderstand one another, and she discusses the problematic
      status of the randomized controlled trial as the "gold standard" of research. She
      urges readers to educate themselves about what the outcome research actually
      shows, to support empirical investigations of psychoanalytic theories and
      practice, to make alliances with therapists of other orientations, and to try to
      contribute to changing the terms in which policymakers and the public frame their
      understanding of mental health and mental suffering. 

PMID- 24325187
TI  - Toward a psychoanalytic way of teaching psychoanalysis.
AB  - The author's orientation to psychoanalytic education blends its subjective and
      objective ways of knowing, its cognitive and experiential aspects. Lear's (2003)
      definition of psychoanalysis as a subjective category contextualizes
      psychoanalytic teaching as a lived-out demonstration of its conceptual learning
      and generates a confident humility in how teachers express theoretical content.
      The author emphasizes teachers' gut-level psychological impacts on candidates,
      and the value of teachers conveying psychoanalytic knowledge as an internalized
      expression of their personal experience and meaning (identification), while
      simultaneously maintaining an objective perspective. A literature review of
      psychoanalytic education and discussion of Stanislavski's (1936, 1949) dramatic
      acting "Method" clarifies the author's pedagogy. 

PMID- 24325191
TI  - Gallic acid is an active component for the anticarcinogenic action of grape seed
      procyanidins in pancreatic cancer cells.
AB  - The aim of the present work was to evaluate the effects of a grape seed
      procyanidin extract (GSPE) on proliferation and apoptosis in the pancreatic
      adenocarcinoma cell line MIA PaCa-2 and identify the components of the extract
      with higher activity. The effects of the extract were analyzed on the
      proliferation and apoptosis processes in MIA PaCa-2 cells, as well as in the
      levels of the apoptosis markers Bcl-2 and Bax, the mitochondrial membrane
      potential, and reactive oxygen species levels. Finally, the components of the
      extract with higher effects were elucidated using enriched fractions of the
      extract and pure compounds. The results showed that GSPE inhibits cell
      proliferation and increases apoptosis in MIA PaCa-2 cells, which is primarily
      mediated by the downregulation of the antiapoptotic protein Bcl-2 and the
      depolarization of the mitochondrial membrane. GSPE also reduced the formation of
      reactive oxygen species. The component of the extract that possesses the highest
      antiproliferative and proapoptotic activity was gallic acid. In conclusion, GSPE
      acts as anticarcinogenic in MIA PaCa-2 cells, with gallic acid as the major
      single active constituent of the extract. 

PMID- 24325192
TI  - The relevance of socio-demographic and occupational variables for the assessment
      of work-related stress risk.
AB  - BACKGROUND: Work-related stress is widely recognized as one of the major
      challenges to occupational health and safety. The correlation between work
      related stress risk factors and physical health outcomes is widely acknowledged.
      This study investigated socio-demographic and occupational variables involved in
      perceived risk of work-related stress. METHODS: The Italian version of the Health
      and Safety Executive Management Standards Indicator Tool was used in a large
      survey to examine the relationship between work-related stress risks and workers'
      demographic and occupational characteristics. Out of 8,527 questionnaires
      distributed among workers (from 75 organizations) 6,378 were returned compiled
      (74.8%); a set of mixed effects models were adopted to test single and combined
      effects of the variables on work-related stress risk. RESULTS: Female workers
      reported lower scores on control and peer support and more negative perceptions
      of relationships and change at work than male workers, most of them with full
      time contracts. Age, job seniority, and educational level appeared positively
      correlated with control at work, but negatively with job demands. Fixed-term
      workers had positive perceptions regarding job demands and relationships, but
      more difficulties about their role at work than permanent workers. A commuting
      time longer than one hour and shift work appeared to be associated with higher
      levels of risk factors for work-related stress (except for role), the latter
      having more negative effects, increasing with age. CONCLUSIONS: The findings
      suggest that the assessment and management of work-related stress risk should
      consider specific socio-demographic and occupational risk factors such as gender,
      age, educational level, job status, shift work, commuting time, job contracts.

PMID- 24325193
TI  - An improved Bacillus subtilis cell factory for producing scyllo-inositol, a
      promising therapeutic agent for Alzheimer's disease.
AB  - BACKGROUND: Bacillus subtilis 168 possesses an efficient pathway to metabolize
      some of the stereoisomers of inositol, including myo-inositol (MI) and scyllo
      inositol (SI). Previously we reported a prototype of a B. subtilis cell factory
      with modified inositol metabolism that converts MI into SI in the culture medium.
      However, it wasted half of initial 1.0% (w/v) MI, and the conversion was limited
      to produce only 0.4% (w/v) SI. To achieve a more efficient SI production, we
      attempted additional modifications. RESULTS: All "useless" genes involved in MI
      and SI metabolism were deleted. Although no elevation in SI production was
      observed in the deletion strain, it did result in no wastage of MI anymore. Thus
      additionally, overexpression of the key enzymes, IolG and IolW, was appended to
      demonstrate that simultaneous overexpression of them enabled complete conversion
      of all MI into SI. CONCLUSIONS: The B. subtilis cell factory was improved to
      yield an SI production rate of 10 g/L/48 h at least. The improved conversion was
      achieved only in the presence of enriched nutrition in the form of 2% (w/v) Bacto
      soytone in the medium, which may be due to the increasing demand for regeneration
      of cofactors.

PMID- 24325194
TI  - Improving dementia diagnosis and management in primary care: a cohort study of
      the impact of a training and support program on physician competency, practice
      patterns, and community linkages.
AB  - BACKGROUND: Primary care physicians routinely provide dementia care, but may lack
      the clinical skills and awareness of available resources to provide optimal care.
      We conducted a community-based pilot dementia training intervention designed to
      both improve clinical competency and increase utilization of local dementia care
      services. METHODS: Physicians (N = 29) and affiliated staff (N = 24) participated
      in a one-day training program on dementia screening, diagnosis and management
      that included direct engagement with local support service providers.
      Questionnaires about their dementia care competency and referral patterns were
      completed before and 6 months after the training intervention. RESULTS:
      Physicians reported significantly higher overall confidence in their dementia
      care competency 6 months post-training compared to pre-training. The largest
      reported improvements were in their ability to educate patients and caregivers
      about dementia and making appropriate referrals to community care services.
      Participants also reported markedly increased use of cognitive screening tools in
      providing care. Community service providers recorded approximately 160 physician
      initiated referrals over a 2 year-period post-training, compared to few
      beforehand. CONCLUSIONS: Combining a targeted physician practice-based
      educational intervention with community service engagement improves dementia care
      competency in clinicians and promotes linkages between clinical and community
      dementia care providers.

PMID- 24325195
TI  - Superior aluminium (Al) tolerance of Stylosanthes is achieved mainly by malate
      synthesis through an Al-enhanced malic enzyme, SgME1.
AB  - Stylosanthes (stylo) is a dominant leguminous forage in the tropics. Previous
      studies suggest that stylo has great potential for aluminium (Al) tolerance, but
      little is known about the underlying mechanism. A novel malic enzyme, SgME1, was
      identified from the Al-tolerant genotype TPRC2001-1 after 72 h Al exposure by two
      dimensional electrophoresis, and the encoding gene was cloned and characterized
      via heterologous expression in yeast, Arabidopsis thaliana and bean (Phaseolus
      vulgaris) hairy roots. Internal Al detoxification might be mainly responsible for
      the 72 h Al tolerance of TPRC2001-1, as indicated by 5.8-fold higher root malate
      concentrations and approximately two-fold higher Al concentrations in roots and
      root symplasts of TPRC2001-1 than those of the Al-sensitive genotype Fine-stem.
      An accompanying increase in malate secretion might also reduce a fraction of Al
      uptake in TPRC2001-1. Gene and protein expression of SgME1 was only enhanced in
      TPRC2001-1 after 72 h Al exposure. Overexpressing SgME1 enhanced malate synthesis
      and rescued yeast, A. thaliana and bean hairy roots from Al toxicity via
      increasing intracellular malate concentrations and/or accompanied malate
      exudation. These results provide strong evidence that superior Al tolerance of
      stylo is mainly conferred by Al-enhanced malate synthesis, functionally
      controlled by SgME1. 

PMID- 24325199
TI  - Profile of bovine proteins in retained and normally expelled placenta in dairy
      cows.
AB  - Tissue-specific protein profile is determined by its function, structure,
      intensity of metabolism and usefulness. This profile remains under hormonal
      control. Any disturbance in the general metabolism may be reflected in changes in
      both protein quantity and quality. These changes can be of low or high
      specificity, and some can be used as clinical markers of pathological conditions.
      The aim of this study was to describe and to compare the protein profile of
      caruncle and foetal villi of bovine placenta that was either properly released or
      retained. Placental tissues were collected from healthy cows, divided into
      releasing and retaining foetal membranes, homogenized and subjected to 1D and 2D
      electrophoresis. Computer-aided analysis of gel images showed essential
      qualitative and quantitative alterations in protein profile between tissues that
      were properly released and retained. Alterations concerned both the number of
      fractions and spots as well as the intensity of staining. This preliminary study
      provides a general overview of the differences in the protein profile between
      released and retained foetal membranes. It may allow for selecting the group of
      proteins or single molecules, which should be further analysed in detail as
      possible markers differentiating the retention of foetal membranes in cows from
      placentas that were released spontaneously. The continuation of the study for the
      identification of particular spots detected in 2D gels is necessary. 

PMID- 24325200
TI  - Introduction: Astrochemistry.

PMID- 24325197
TI  - Thiazolidinediones and associated risk of bladder cancer: a systematic review and
      meta-analysis.
AB  - AIMS: To determine whether thiazolidinedione use is associated with a risk of
      bladder cancer. METHODS: We searched MEDLINE and EMBASE in June 2012 (with PubMed
      update to July 2013) and conducted meta-analysis on the overall risks of bladder
      cancer with pioglitazone or rosiglitazone and the risk with different categories
      of cumulative dose or duration of drug use. RESULTS: We screened 230 citations
      and included 18 studies, comprising five randomized controlled trials (RCTs) and
      13 observational studies. Meta-analysis showed a significantly higher overall
      risk of bladder cancer with pioglitazone in RCTs [7878 participants; odds ratio
      (OR) 2.51, 95% confidence interval (CI) 1.09-5.80] and observational studies
      (>2.6 million patients; OR for 'ever' users vs. non-users 1.21, 95% CI 1.09
      1.35). Subgroup analysis of observational studies by cumulative dose showed the
      risk of bladder cancer to be greatest with >28.0 g of pioglitazone (OR 1.64, 95%
      CI 1.28-2.12). A significantly increased risk was found with both 12-24 months
      (OR 1.41, 95% CI 1.16-1.71) and >24 months (OR 1.51, 95% CI 1.26-1.81) cumulative
      durations of pioglitazone exposure. No significant risk was seen with
      rosiglitazone in RCTs (OR 0.84, 95% CI 0.35-2.04) or 'ever' users vs. non-users
      in observational studies (OR 1.03, 95% CI 0.94-1.12); the evidence for any
      relationship between bladder cancer risk and rosiglitazone cumulative duration is
      limited and inconsistent. Direct comparison of pioglitazone to rosiglitazone
      'ever' users yielded an OR of 1.25 (95% CI 0.91-1.72). CONCLUSIONS: A modest but
      clinically significant increase in the risk of bladder cancer with pioglitazone
      was found, which appears to be related to cumulative dose and duration of
      exposure. We recommend that prescribers limit pioglitazone use to shorter
      durations.

PMID- 24325201
TI  - Treatment efficacy of pegylated interferon plus ribavirin therapy in chronic
      hepatitis C patients with mixed genotype 1/2 infection.
AB  - BACKGROUND AND AIM: The treatment efficacy of patients with mixed hepatitis C
      virus (HCV) genotype 1/genotype 2 (HCV-1/2) remains unknown. We aimed to
      elucidate the sustained virological response (SVR) rate in patients with HCV-1/2
      infection. METHODS: One hundred and ten HCV-1/2 patients treated with response
      guided peginterferon/ribavirin therapy (24 weeks for patients with a rapid
      virological response [RVR] and low viral loads; 48 weeks for patients without a
      RVR or high viral loads) were allocated. Two hundred HCV-1 patients were selected
      as a historical control. Interleukin-28B (IL-28B) rs8099917 genotype was tested
      for the association with an SVR. RESULTS: The rates of RVR, sustained virologic
      response (SVR), and relapse rate were 71.8%, 87.3%, and 11.1%, respectively. The
      SVR rate was significantly higher in patients with an abbreviated regimen as
      compared with those with 48-week regimen (95.5% vs 75.0%, P = 0.002), and both
      were similar to the HCV-1 historical control. Stepwise logistic regression
      analysis revealed that lower baseline viral loads were the single factor
      predictive of an RVR (odds ratio/95% confidence intervals [OR/CI] of 41.62/9.72
      178.19, P < 0.001). The achievement of an RVR was the single best factor
      predictive of an SVR (OR/CI: 7.5/1.33-42.27, P = 0.02). Nevertheless, an
      abbreviated regimen became the single factor associated with an SVR if treatment
      regimen was taken into consideration (OR/CI: 11.0/1.25-96.79, P = 0.03). The SVR
      rate did not differ between patients with rs8099917 TT and TG/GG genotype (91.7%
      vs 87.5%, P = 0.63). CONCLUSIONS: The treatment efficacy of patients with HCV-1/2
      was satisfactory. The role of IL-28B genetic variants in the population with
      response-guided therapy was limited.

PMID- 24325202
TI  - Muscle-invasive bladder cancer: evaluating treatment and survival in the National
      Cancer Data Base.
AB  - OBJECTIVE: To evaluate the association between patterns of care and patient
      survival for the treatment of muscle-invasive bladder cancer (MIBC) using a
      large, national database. PATIENTS AND METHODS: We identified a cohort of 36,469
      patients with MIBC (stage II) from 1998 to 2010 from the National Cancer Data
      Base. Patients were stratified into four treatment groups: radical cystectomy,
      chemo-radiation, other therapy, or no treatment. Overall survival (OS) among the
      groups was evaluated using Kaplan-Meier analysis and the log rank test. A
      multivariable Cox proportional hazards model was fit to evaluate the association
      between treatment groups and OS. RESULTS: In all, 27% of patients received
      radical cystectomy, 10% chemo-radiation, 61% other therapy and 2% no treatment.
      Unadjusted Kaplan-Meier analysis showed significant differences by treatment
      group, with cystectomy having the greatest median OS (48 months) followed by
      chemo-radiation (28 months), other therapy (20 months), and no treatment (5
      months). When controlling for multiple covariates, the OS for cystectomy was
      similar to that for chemo-radiation (hazard ratio [HR] 1.05, 95% confidence
      interval [CI] 0.98, 1.12), but superior to other therapy (HR 1.42; 95% CI 1.35,
      1.48), and no treatment (HR 2.40; 95% CI 2.12, 2.72). The OS time for chemo
      radiation was superior to other therapy and no treatment. CONCLUSIONS: Radical
      cystectomy and chemo-radiation are significantly underused despite a substantial
      survival benefit compared with other therapies or no treatment. Future studies
      are needed to optimise care delivery and improve outcomes for patients with MIBC.

PMID- 24325203
TI  - Usefulness of proton and phosphorus MR spectroscopic imaging for early diagnosis
      of Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Cerebral mitochondrial dysfunction has been observed in
      Parkinson's disease (PD). If mitochondrial dysfunction is an early event
      contributing to PD development, then noninvasive techniques that detect disturbed
      energy metabolism in vivo might be useful tools for early diagnosis and treatment
      monitoring. In the present study, we tested the hypothesis that proton ((1) H)
      and phosphorus ((31) P) magnetic resonance spectroscopy (MRS) measures of brain
      metabolites are able to differentiate between individuals with early PD and
      healthy volunteers (HVs). METHODS: During this cross-sectional study including 20
      subjects with early PD and 15 age-matched HV, ventricular lactate (anaerobic
      glycolysis); and regional levels of N-acetylaspartate (neuronal integrity);
      choline (membrane turnover); creatine (energy metabolism); ATP and other
      phosphate-containing compounds (oxidative phosphorylation) were determined using
      brain (1) H and (31) P MRS. RESULTS: No metabolic abnormalities were detectable
      in early-stage PD patients. Metabolite concentrations were not related to age,
      disease duration, or Unified Parkinson's Disease Rating Scale motor scores.
      DISCUSSION: In early PD, neither (1) H nor (31) P MRS were able to detect
      metabolic abnormalities, a finding that is in contrast to published data in more
      advanced PD cohorts. MRS under dynamic conditions might uncover latent energy
      deficits in early PD, thus warranting future study.

PMID- 24325204
TI  - High sensitivity of quick view capsule endoscopy for detection of small bowel
      Crohn's disease.
AB  - BACKGROUND AND AIM: Capsule endoscopy (CE) has a high sensitivity for diagnosing
      small bowel Crohn's disease, but video analysis is time-consuming. The quick view
      (qv) function is an effective tool to reduce time consumption. The aim of this
      study was to determine the rate of missed small bowel ulcerations with qv-CE
      compared with standard view and the diagnostic accuracy of qv-CE in suspected
      Crohn's disease. METHODS: This study consisted of two parts: (i) 12 small bowel
      segments with Crohn's disease of varying severity were selected for a detailed
      analysis of the number and type of lesions visualized with CE and qv-CE, and (ii)
      a blinded study of the diagnostic accuracy of qv-CE including 40 patients with
      suspected Crohn's disease. Ileocolonoscopy and CE served as gold standard.
      RESULTS: Part 1: CE visualized 171 ulcerations compared with 102 detected with qv
      CE (miss rate 40%, P = 0.02). Part 2: qv-CE identified 15 of 16 patients with
      small bowel Crohn's disease corresponding to a 94% sensitivity, and overall, 39
      out of 40 patients were classified correct (diagnostic accuracy 98%). Qv-CE was
      false negative in one patient because of a leap of 3 min and 20 s in the terminal
      ileum. Reading times varied from 5 to 18 min (median 10). CONCLUSION: Despite a
      significant number of missed lesions, qv-CE is a safe and time-reducing method
      for diagnosing small bowel Crohn's disease. To avoid false negative cases, we
      recommend viewing the terminal ileum in standard view.

PMID- 24325205
TI  - Small and ugly? Phylogenetic analyses of the "selfing syndrome" reveal complex
      evolutionary fates of monomorphic primrose flowers.
AB  - One of the most common trends in plant evolution, loss of self-incompatibility
      and ensuing increases in selfing, is generally assumed to be associated with a
      suite of phenotypic changes, notably a reduction of floral size, termed the
      selfing syndrome. We investigate whether floral morphological traits indeed
      decrease in a deterministic fashion after losses of self-incompatibility, as
      traditionally expected, using a phylogeny of 124 primrose species containing nine
      independent transitions from heterostyly (heteromorphic incompatibility) to
      homostyly (monomorphic self-compatibility), a classic system for evolution of
      selfing. We find similar overall variability of homostylous and heterostylous
      species, except for diminished herkogamy in homostyles. Bayesian mixed models
      demonstrate differences between homostylous and heterostylous species in all
      traits, but net effects across species are small (except herkogamy) and
      directionality differs among traits. Strongly drift-like evolutionary
      trajectories of corolla tube length and corolla diameter inferred by Ornstein
      Uhlenbeck models contrast with expected deterministic trajectories toward small
      floral size. Lineage-specific population genetic effects associated with
      evolution of selfing may explain that reductions of floral size represent one of
      several possible outcomes of floral evolution after loss of heterostyly in
      primroses. Contrary to the traditional paradigm, selfing syndromes may, but do
      not necessarily evolve in response to increased selfing. 

PMID- 24325206
TI  - Pilot evaluation of an integrated monitor-adhesive patch for long-term cardiac
      arrhythmia detection in India.
AB  - Electrocardiographic monitoring represents one of the most reliable and time
      tested methods for reducing ambiguity in cardiac arrhythmia diagnosis. In India,
      the resting ECG is generally the first tool of choice for in-clinic diagnosis.
      The external loop recorder (ELR) is another useful tool that compounds the
      advantages of traditional tools by coupling ambulatory monitoring with a long
      term window. Thus, the objective was to test the use of a 7-day ELR for
      arrhythmia diagnosis in India for a broad range of presenting symptoms. In this
      study set in the Indian healthcare environment, an auto-triggered, wireless patch
      type ELR was used with 125 patients (62.5 +/- 16.7 years, 76 males) presenting a
      broad range of symptoms. Eighty percent of the symptoms were related to syncope,
      presyncope or palpitations. Patients were administered an ELR for 7-28 days
      depending on the physician's prescription. Prespecified significant arrhythmias
      included sinus pause >2 s, symptomatic bradycardia <40 b.p.m., second-degree (and
      higher) AV block, complete heart block, ventricular fibrillation,
      sustained/nonsustained ventricular tachycardia (>3 beats), atrial fibrillation
      (chronic or paroxysmal), atrial flutter and supraventricular tachycardia (SVT)
      >130 b.p.m. Diagnostic yield was 38% when a stringent tabulation methodology
      considering only clinically significant arrhythmia was used. When first-degree AV
      block, premature atrial and ventricular beats, couplets (both atrial and
      ventricular in origin), bigeminy or trigeminy, or sudden changes in rate (noted
      as sinus arrhythmia) were included in the calculation, diagnostic yield was 80%.
      Patient compliance was 98%; patients wore the patch for the entire prescribed
      monitoring period without disruption. Seventy percent of the reported symptoms
      corresponded with an arrhythmia. Use of the ELR led to therapy change in 24% of
      patients: 15 patients went on to receive an implantable cardioverter
      defibrillator or pacemaker, 4 received ablation therapy and 11 altered their
      medication after diagnosis. This study demonstrates that a high diagnostic yield
      for clinically significant arrhythmias and high patient compliance can be
      achieved with a wearable patch monitor in Indian patients suffering from a
      variety of symptoms. 

PMID- 24325207
TI  - Combination of degradation pathways for naphthalene utilization in Rhodococcus
      sp. strain TFB.
AB  - Rhodococcus sp. strain TFB is a metabolic versatile bacterium able to grow on
      naphthalene as the only carbon and energy source. Applying proteomic, genetic and
      biochemical approaches, we propose in this paper that, at least, three
      coordinated but independently regulated set of genes are combined to degrade
      naphthalene in TFB. First, proteins involved in tetralin degradation are also
      induced by naphthalene and may carry out its conversion to salicylaldehyde. This
      is the only part of the naphthalene degradation pathway showing glucose
      catabolite repression. Second, a salicylaldehyde dehydrogenase activity that
      converts salicylaldehyde to salicylate is detected in naphthalene-grown cells but
      not in tetralin- or salicylate-grown cells. Finally, we describe the
      chromosomally located nag genes, encoding the gentisate pathway for salicylate
      conversion into fumarate and pyruvate, which are only induced by salicylate and
      not by naphthalene. This work shows how biodegradation pathways in Rhodococcus
      sp. strain TFB could be assembled using elements from different pathways mainly
      because of the laxity of the regulatory systems and the broad specificity of the
      catabolic enzymes.

PMID- 24325208
TI  - Antibiotic use and resistance in emerging economies: a situation analysis for
      Viet Nam.
AB  - BACKGROUND: Antimicrobial resistance is a major contemporary public health
      threat. Strategies to contain antimicrobial resistance have been comprehensively
      set forth, however in developing countries where the need for effective
      antimicrobials is greatest implementation has proved problematic. A better
      understanding of patterns and determinants of antibiotic use and resistance in
      emerging economies may permit more appropriately targeted interventions.Viet Nam,
      with a large population, high burden of infectious disease and relatively
      unrestricted access to medication, is an excellent case study of the difficulties
      faced by emerging economies in controlling antimicrobial resistance. METHODS: Our
      working group conducted a situation analysis of the current patterns and
      determinants of antibiotic use and resistance in Viet Nam. International
      publications and local reports published between 1-1-1990 and 31-8-2012 were
      reviewed. All stakeholders analyzed the findings at a policy workshop and
      feasible recommendations were suggested to improve antibiotic use in Viet
      Nam.Here we report the results of our situation analysis focusing on: the
      healthcare system, drug regulation and supply; antibiotic resistance and
      infection control; and agricultural antibiotic use. RESULTS: Market reforms have
      improved healthcare access in Viet Nam and contributed to better health outcomes.
      However, increased accessibility has been accompanied by injudicious antibiotic
      use in hospitals and the community, with predictable escalation in bacterial
      resistance. Prescribing practices are poor and self-medication is common - often
      being the most affordable way to access healthcare. Many policies exist to
      regulate antibiotic use but enforcement is insufficient or lacking.Pneumococcal
      penicillin-resistance rates are the highest in Asia and carbapenem-resistant
      bacteria (notably NDM-1) have recently emerged. Hospital acquired infections,
      predominantly with multi-drug resistant Gram-negative organisms, place additional
      strain on limited resources. Widespread agricultural antibiotic use further
      propagates antimicrobial resistance. CONCLUSIONS: Future legislation regarding
      antibiotic access must alter incentives for purchasers and providers and ensure
      effective enforcement. The Ministry of Health recently initiated a national
      action plan and approved a multicenter health improvement project to strengthen
      national capacity for antimicrobial stewardship in Viet Nam. This analysis
      provided important input to these initiatives. Our methodologies and findings may
      be of use to others across the world tackling the growing threat of antibiotic
      resistance.

PMID- 24325210
TI  - Education in the responsible conduct of research in psychology: methods and
      scope.
AB  - In this mixed-method study of education in the responsible conduct of research
      (RCR) in psychology, phase one survey respondents (n = 141) reported that faculty
      and students were familiar with RCR standards and procedures to educate them were
      believed to be adequate. However, educational methods varied widely. In phase
      two, seven survey respondents completed in-depth interviews assessing RCR
      training and education and research review procedures. Educational methods
      through which RCR content was presented included the following ones: traditional
      (lectures), technical (web-based), and experiential (internships), but RCR was
      often minimally considered in the formal curriculum. Our results suggest that
      psychology training programs might benefit from more formal consideration of RCR
      education and training in the curriculum. 

PMID- 24325211
TI  - Perspectives on whistleblowing: faculty member viewpoints and suggestions for
      organizational change.
AB  - Given the prevalence of unethical behavior in research, whistleblowing may serve
      an important policing function. Despite this potential value of whistleblowing to
      organizations, engaging in this type of activity often has negative ramifications
      for those who choose to blow the whistle. Organizations may fail to provide
      adequate support for these individuals. In order to help inform best practices
      for organizations in terms of whistleblowing support infrastructure, the present
      effort content analyzed interviews with university faculty members regarding
      ethical decision making in which whistleblowing was a topic. Relevant themes in
      these interviews are discussed. 

PMID- 24325212
TI  - Self-plagiarism and textual recycling: legitimate forms of research misconduct.
AB  - The concept of self-plagiarism frequently elicits skepticism and generates
      confusion in the research ethics literature, and the ethical status of what is
      often called "textual recycling" is particularly controversial. I argue that, in
      general, self-plagiarism is unethical because it is deceptive and dishonest. I
      then distinguish several forms of it and argue against various common
      rationalizations for textual recycling. I conclude with a discussion of two
      instances of textual recycling, distinguishing them in terms of their ethical
      seriousness but concluding that both are ethically problematic. 

PMID- 24325213
TI  - Analysis and implications of retraction period and coauthorship of fraudulent
      publications.
AB  - Studies have indicated that the number and frequency of fraudulent publications
      being retracted are not subsiding even with greater awareness of such incidents
      in the recent decades. In this study, the trends of retraction period, number of
      citations and coauthors of 5 selected researchers who had >= 15 fraudulent
      publications retracted were analyzed. The obtained results shows that the
      retraction period is 48.96 +/- 32.16 months for the 113 publications affiliated
      to the 5 studied researchers. There are a total of 180 coauthors with 6.40 +/-
      3.26 coauthors per researcher's retracted publication. The linear regression
      analysis indicates that there is limited correlation (R(2) = .008) between the
      citation counts and retraction period. The p value for multiple F-tests to assess
      the number of coauthors to a fraudulent publication on an interresearcher basis
      is found to be ranging from < .001 to .458. It is also found that a better
      correlation (R(2) = .592) exists between the likelihood of a researcher to
      involve different individuals for isolated fraudulent publications while only
      selecting very few to be their frequent coauthors of their mischievous acts. With
      this study, the possible use of coauthors as a strategy for publishing fraudulent
      work and a potential approach to tighten coauthorship are discussed. 

PMID- 24325214
TI  - Expression of MACC1 and c-Met in human gastric cancer and its clinical
      significance.
AB  - BACKGROUND: Recent studies have suggested that the metastasis-associated colon
      cancer1 (MACC1) gene can promote tumor proliferation, invasion and metastasis
      through an upregulation of c-Met expression. However, its role in gastric cancer
      is controversial. Our study investigated expression of MACC1 and c-Met in gastric
      cancer, as well as correlated this with clinicopathological parameters. METHODS:
      Expressions of MACC1 and c-Met protein in a sample of 98 gastric carcinoma and
      adjacent nontumorous tissues were detected by immunohistochemistry. Their
      relationships and correlations with clinicopathological features were analyzed.
      RESULTS: The positive rates of MACC1 and c-Met protein in primary tumors were
      61.22% and 59.18%, respectively. A significant correlation was found between
      expression of MACC1 and c-Met (P<0.05). Expression of the MACC1 protein in
      gastric cancer tissue was correlated with lymph node metastasis (chi2 = 10.555,P
      = 0.001), peritoneal metastasis (chi2 = 5.694, P = 0.017), and hepatic metastasis
      (chi2 = 4.540,P = 0.033), but not with age, gender, tumor size, location,
      clinical stage or the distant metastases (P>0.05). CONCLUSION: The positive rate
      of MACC1 protein expression was related to the protein expression of c-Met. Both
      had a correlation with the presence of peritoneal metastasis, lymph node
      metastasis and hepatic metastasis, all of which contribute to a poor prognosis
      for gastric cancer patients.

PMID- 24325215
TI  - Nicorandil infusion during inter-hospital transfer of patients with acute
      coronary syndrome--what can we do in a rural area of Japan?

PMID- 24325216
TI  - Lower incidence of CMV infection and acute rejections with valganciclovir
      prophylaxis in lung transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection
      following lung transplantation. CMV replication in the lung allograft is
      described as accelerating the development of bronchiolitis obliterans syndrome
      (BOS). Finding a strategy to prevent CMV infection is an important issue.
      METHODS: We performed a retrospective, single-centre study of 114 lung transplant
      recipients (LTRs) who underwent lung transplantation from January 2001 to
      December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months
      of valganciclovir prophylaxis (2004-2006) was compared to three months of oral
      ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease,
      the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year
      survival. In the whole group of 114 LTRs the impact of CMV infection on long-term
      survival (BOS free 4 year survival and 6 year survival) was assessed. RESULTS:
      For the cohort of 88 CMV seropositive LTRs, the incidence of CMV
      infection/disease at one year was lower in the valganciclovir group compared to
      the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards
      reduced CMV disease, from 33% to 20% and a significant lower incidence of
      asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute
      rejection was observed in the valganciclovir group. However, there was no
      significant difference between the two groups in BOS free 4 year survival and 4
      year survival.For the entire group of 114 LTRs, BOS-free 4 year survival for
      recipients with CMV disease was (32%, p = 0.005) and among those with
      asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV
      infection (69%). Six year survival was lower among patients with CMV disease,
      (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients
      without CMV infection (84%). CONCLUSIONS: A lower incidence of CMV
      infection/disease and acute rejections was observed with valganciclovir (3
      months) when compared to oral ganciclovir (3 months). The long-term impact of CMV
      infection/disease was significant for BOS-free survival and survival.

PMID- 24325217
TI  - Zinc status alters growth and oxidative stress responses in rat hepatoma cells.
AB  - Zinc deficiency and excess influence cellular homeostasis and are believed to
      modulate apoptosis. Zinc also regulates cell growth and proliferation.
      Understanding of the role of zinc in the mechanisms associated with these changes
      is limited because of its diverse, complex, and cell-specific effects. Therefore,
      we investigated the oxidative stress responses and the underlying molecular
      mechanisms associated with the disruption of intracellular zinc homeostasis in
      H4IIE rat hepatoma cells. We found that zinc excess (100 MUM) and DTPA
      (diethylenetriaminepentaacetic acid; 50-100 MUM) induced zinc deficiency both
      generate reactive oxygen species (ROS) and decrease viability in H4IIE cells.
      However, cotreatment with the antioxidant, N-acetyl-L-cysteine (NAC) both reduced
      ROS production and protected cells from death. We additionally observed an
      increase in Bax mRNA and cytochrome c release from the mitochondria in DTPA
      treated cells and an elevated expression of Fas/Fas ligand mRNA with zinc
      treatment. Both treatments increased p53 and MdM2 protein concentrations along
      with caspase 3/7 activity. These results suggest that zinc deficiency stimulates
      mitochondrial-dependent apoptosis whereas zinc activates the extrinsic-apoptotic
      pathway. Both decreasing and increasing cellular zinc concentrations modulate ROS
      mediated apoptosis and warrant further research on zinc mediated cancer
      chemoprevention in this and other cancer cell lines. 

PMID- 24325218
TI  - Biomarkers in schizophrenia.

PMID- 24325219
TI  - Precompetitive consortium approach to validation of the next generation of
      biomarkers in schizophrenia.

PMID- 24325222
TI  - The use of proteomic biomarkers for improved diagnosis and stratification of
      schizophrenia patients.
AB  - Schizophrenia is characterized by a wide spectrum of clinical manifestations,
      including strong effects on mood and behavior. Patients can also suffer from
      serious comorbidities including immune system or metabolic abnormalities. Recent
      advances using proteomic profiling approaches have increased our understanding of
      these molecular effects and have laid the groundwork for unraveling the
      heterogeneity of this broadly defined disease. These findings could lead to
      improved diagnosis and stratification of patients through identification of
      biochemically different disease subtypes and personalized medicine approaches.
      The inclusion of molecular signatures in psychiatry will be an important leap
      forward in providing more effective treatment of patients suffering from this
      debilitating disorder. 

PMID- 24325223
TI  - Use of translational pharmacodynamic biomarkers in early-phase clinical studies
      for schizophrenia.
AB  - Schizophrenia is a severe mental disorder characterized by cognitive deficits,
      and positive and negative symptoms. The development of effective pharmacological
      compounds for the treatment of schizophrenia has proven challenging and costly,
      with many compounds failing during clinical trials. Many failures occur due to
      disease heterogeneity and lack of predictive preclinical models and biomarkers
      that readily translate to humans during early characterization of novel
      antipsychotic compounds. Traditional early-phase trials consist of single- or
      multiple-dose designs aimed at determining the safety and tolerability of an
      investigational compound in healthy volunteers. However, by incorporating a
      translational approach employing methodologies derived from preclinical studies,
      such as EEG measures and imaging, into the traditional Phase I program, critical
      information regarding a compound's dose-response effects on pharmacodynamic
      biomarkers can be acquired. Furthermore, combined with the use of patients with
      stable schizophrenia in early-phase clinical trials, significant 'de-risking' and
      more confident 'go/no-go' decisions are possible. 

PMID- 24325220
TI  - Using biomarkers to inform diagnosis, guide treatments and track response to
      interventions in psychotic illnesses.

PMID- 24325224
TI  - Biomarkers in psychosis: an approach to early identification and individualized
      treatment.
AB  - Numerous biomarkers for somatic disorders are used in routine medical practice.
      Yet, despite remarkable advances in mental health research, we are not able to
      identify biomarkers with established clinical utility for mental disorders such
      as schizophrenia. While identification and characterization of biomarkers are
      crucial first steps in this process, their predictive diagnostic and treatment
      utility need to be better developed for clinical practice. The heterogeneity of
      psychotic disorders etiologically, pathologically and symptomatically presents
      both a challenge and an opportunity for the use of biomarkers in clinical
      practice. Simply said, a single biomarker might not exist that necessitates the
      search for a biomarker profile. In this review we discuss research findings in
      light of such an approach. We summarize some examples of emerging biomarkers in
      early psychosis research and delineate how these can be applied to a clinical
      setting to inform treatment on an individual basis fostering a personalized
      treatment approach. 

PMID- 24325225
TI  - Unresolved questions in Alzheimer's research: will biomarkers help?

PMID- 24325226
TI  - Biomarkers for fatal immune response to stem cell treatment could reduce
      mortality.

PMID- 24325229
TI  - Predicting the chance of relapse after tamoxifen treatment in breast cancer.

PMID- 24325230
TI  - Current and future roles of biochemical biomarkers in hypertrophic
      cardiomyopathy.

PMID- 24325231
TI  - Urinary biomarkers track the progression of nephropathy in hypertensive and obese
      rats.
AB  - AIMS: To determine whether urinary biomarkers of acute kidney injury can be used
      to monitor the progression of chronic kidney injury in a rat model of
      hypertension and obesity. MATERIALS & METHODS: A suite of novel urinary
      biomarkers were used to track the progression of kidney damage in SHROB and SHR
      lean rats. RESULTS: Urinary albumin, NAG, clusterin, osteopontin, RPA-1 and
      fibrinogen levels were significantly elevated over time and were closely
      associated with the severity of histopathologically determined nephropathy in
      both SHROB and SHR-lean rats. CONCLUSION: Urinary biomarkers, such as albumin,
      fibrinogen, NAG, clusterin, RPA-1 and osteopontin, may serve as useful tools to
      track the progression of chronic kidney disease associated with hypertension and
      obesity.

PMID- 24325232
TI  - Resistin as a biomarker linking obesity and inflammation to cancer: potential
      clinical perspectives.
AB  - Excess body weight is associated with various types of malignancies. Resistin,
      originally described as an adipocyte-specific hormone modulating insulin
      resistance in rodents, may exhibit proliferative, antiapoptotic, proinflammatory,
      proangiogenic and metastatic properties. Accumulating evidence supports a role of
      resistin as a risk factor and potential diagnostic and prognostic biomarker in
      cancer. In this report, the current knowledge about resistin's properties and
      pathophysiological implications in cancer in the context of dysregulated adipose
      tissue in obesity is summarized; clinical translations, preventive and
      therapeutic considerations, and future perspectives in the field of resistin
      research are discussed. At the same time, several enigmatic issues involving
      resistin receptor and signaling pathways remain to be clarified in order to
      unmask its ontological role in cancer pathophysiology. 

PMID- 24325233
TI  - Advances in technologies for screening and diagnosis of hemoglobinopathies.
AB  - Hemoglobinopathies constitute the most common monogenic disorders worldwide,
      caused by mutations in the globin genes that synthesize the globin chains of
      hemoglobin. Synthesis may be reduced (thalassemia) or underlie abnormal
      hemoglobins. Mutation interactions produce a wide range of disorders. For
      neonatal and antenatal screening, identification of affected newborns or carriers
      is achieved by hematological tests. DNA analysis supports definitive diagnosis,
      and additionally facilitates prenatal diagnosis procedures. Most methods used
      today have been developed over several decades, with few recent advances in
      hematology methods. However, DNA methods evolve continuously. With global
      migration and multiethnic societies the trend is from targeted, population
      specific methods towards generic methods, such as Sanger sequencing (point
      mutations) and multiplex ligation probe amplification (deletions). DNA
      microarrays constitute an advanced DNA method for some mutation categories. The
      newest DNA technology is next-generation sequencing. Although not completely
      ready for routine use currently, next-generation sequencing may soon become a
      reality for some hemoglobin diagnostic laboratories. 

PMID- 24325234
TI  - Chromogranin A as a biomarker in cardiovascular disease.
AB  - Chromogranin A is known as an important marker of neuroendocrine tumors. In
      cardiovascular medicine, however, chromogranin A measurement has only recently
      gained interest, since increased concentrations in the circulation are associated
      with risk of clinical worsening and death in patients with acute coronary
      syndromes or chronic heart failure. In this article, we summarize the current
      clinical data on chromogranin A as a biomarker in cardiovascular disease from
      high-risk conditions; for example, obesity, hypertension and diabetes, to overt
      heart failure. Biological activity of the various chromogranin A fragments,
      including the intact precursor itself, will not be covered in the present review.
      Instead, we highlight the complexity of chromogranin A as a plasma marker, where
      the protein is extensively and variably processed to a plethora of peptide
      fragments. Current immunological methods for clinical measurement differ
      dramatically with respect to both epitope choice and clinical validation. 

PMID- 24325235
TI  - The symbiotic transcription factor MtEFD and cytokinins are positively acting in
      the Medicago truncatula and Ralstonia solanacearum pathogenic interaction.
AB  - * A plant-microbe dual biological system was set up involving the model legume
      Medicago truncatula and two bacteria, the soil-borne root pathogen Ralstonia
      solanacearum and the beneficial symbiont Sinorhizobium meliloti. * Comparison of
      transcriptomes under symbiotic and pathogenic conditions highlighted the
      transcription factor MtEFD (Ethylene response Factor required for nodule
      Differentiation) as being upregulated in both interactions, together with a set
      of cytokinin-related transcripts involved in metabolism, signaling and response.
      MtRR4 (Response Regulator), a cytokinin primary response gene negatively
      regulating cytokinin signaling and known as a target of MtEFD in nodulation
      processes, was retrieved in this set of transcripts. * Refined studies of MtEFD
      and MtRR4 expression during M. truncatula and R. solanacearum interaction
      indicated differential kinetics of induction and requirement of central
      regulators of bacterial pathogenicity, HrpG and HrpB. Similar to MtRR4, MtEFD
      upregulation during the pathogenic interaction was dependent on cytokinin
      perception mediated by the MtCRE1 (Cytokinin REsponse 1) receptor. * The use of
      M. truncatula efd-1 and cre1-1 mutants evidenced MtEFD and cytokinin perception
      as positive factors for bacterial wilt development. These factors therefore play
      an important role in both root nodulation and root disease development.

PMID- 24325236
TI  - Diagnosis of famine: a discursive contribution.
AB  - This paper recommends the incorporation of an additional discursive dimension in
      famine diagnosis that draws on the number of reports referring to famine in the
      United Nations Office for the Coordination of Humanitarian Affairs (OCHA)'s
      ReliefWeb database. Present-day diagnostic tools already apply the principle of
      triangulation with multiple indicators; the addition of a discursive diagnostic
      dimension would enable even more refined analysis, allowing more forcefully for
      the incorporation of the aspect of change. The newly devised discursive famine
      indices are used both to identify famines--in Ethiopia (2000), Malawi (2002), and
      Somalia (2011)--and to analyse key socioeconomic determinants of famine. The
      study finds that income (or poverty) together with state fragility appear to be
      the major determinants of cross-country variations in famine reporting, while
      political regimes do not appear to have any independent effect. The indices
      appear largely robust with regard to concerns about cross-country, semantic, and
      temporal biases.

PMID- 24325237
TI  - The analytical framework of water and armed conflict: a focus on the 2006 Summer
      War between Israel and Lebanon.
AB  - This paper develops an analytical framework to investigate the relationship
      between water and armed conflict, and applies it to the 'Summer War' of 2006
      between Israel and Lebanon (Hezbollah). The framework broadens and deepens
      existing classifications by assessing the impact of acts of war as indiscriminate
      or targeted, and evaluating them in terms of international norms and law, in
      particular International Humanitarian Law (IHL). In the case at hand, the
      relationship is characterised by extensive damage in Lebanon to drinking water
      infrastructure and resources. This is seen as a clear violation of the letter and
      the spirit of IHL, while the partial destruction of more than 50 public water
      towers compromises water rights and national development goals. The absence of
      pre-war environmental baselines makes it difficult to gauge the impact on water
      resources, suggesting a role for those with first-hand knowledge of the
      hostilities to develop a more effective response before, during, and after armed
      conflict. 

PMID- 24325238
TI  - Constructing a holistic approach to disaster risk reduction: the significance of
      focusing on vulnerability reduction.
AB  - As a result of the increase in natural disaster losses, policy-makers,
      practitioners, and members of the research community around the world are seeking
      effective and efficient means of overcoming or minimising them. Although various
      theoretical constructs are beneficial to understanding the disaster phenomenon
      and the means of minimising losses, the disaster risk management process becomes
      less effective if theory and practice are set apart from one another.
      Consequently, this paper seeks to establish a relationship between two
      theoretical constructs, 'disaster risk reduction (DRR)' and 'vulnerability
      reduction', and to develop a holistic approach to DRR with particular reference
      to improving its applicability in practical settings. It is based on a literature
      review and on an overall understanding gained through two case studies of post
      disaster infrastructure reconstruction projects in Sri Lanka and three expert
      interviews in Sri Lanka and the United Kingdom. 

PMID- 24325239
TI  - Behavioural, emotional, and cognitive responses in European disasters: results of
      survivor interviews.
AB  - In the European multi-centre study BeSeCu (Behaviour, Security, Culture),
      interviews were conducted in seven countries to explore survivors' emotional,
      behavioural, and cognitive responses during disasters. Interviews, either in
      groups or one-to-one, were convened according to type of event: collapse of a
      building; earthquake; fire; flood; and terror attack. The content analysis of
      interviews resulted in a theoretical framework, describing the course of the
      events, behavioural responses, and the emotional and cognitive processing of
      survivors. While the environmental cues and the ability to recognise what was
      happening varied in different disasters, survivors' responses tended to be more
      universal across events, and most often were adaptive and non-selfish. Several
      peri-traumatic factors related to current levels of post-traumatic stress were
      identified, while memory quantity did not differ as a function of event type or
      post-traumatic stress. Time since the event had a minor effect on recall. Based
      on the findings, several suggestions for emergency training are made. 

PMID- 24325240
TI  - Decision-making behaviour during urban search and rescue: a case study of
      Germany.
AB  - The objective of assisting with tasks and decisions during incident response is
      to reduce the risks to victims and rescue personnel while increasing the
      efficiency of the rescue operation. Handling uncertain information during urban
      search and rescue (USAR) missions represents additional stress to the decision
      maker. The aim of this study is to identify the decision-making behaviour of
      rescuers during USAR missions to pinpoint trapped or buried victims in debris in
      order to design assistance technologies and decision-support systems that meet
      their needs. In 2010, a survey was conducted among 10-15 per cent of all German
      rescue personnel specialised in search tasks. One of the major results of this
      survey is that a subjective assessment of the reliability of information
      available from heterogeneous sources influences the rescuers' actions and that
      there is no methodology for decision-making involving uncertain information. In
      addition, the study found that compliance with procedures does not require
      assistance. 

PMID- 24325241
TI  - The feasibility of concentrated rural settlement in a context of post-disaster
      reconstruction: a study of China.
AB  - There is growing appreciation of the use of concentrated rural settlement as an
      effective means of implementing infrastructure projects and helping to achieve
      sustainable development in rural areas. This occurs in China through the exchange
      of rural residential land for urban construction. However, this policy has not
      been effective under normal circumstances (called development-driven conditions)
      as frequently farmers are reluctant to accept such an exchange. By contrast, in a
      time of disaster, such as after the 2008 earthquake in Sichuan Province, China,
      rural victims have accepted this policy of rural residential land exchange.
      Employing game theory, this paper identifies the reasons for the different
      outcomes and it contends that the implementation of concentrated rural settlement
      practice under disaster-induced conditions is more effective than its
      introduction under development-driven conditions. The results of the analysis
      indicate that, in China, concentrated rural settlement is feasible in a context
      of post-disaster reconstruction. 

PMID- 24325242
TI  - Collaborative modelling-based shelter planning analysis: a case study of the
      Nagata Elementary School Community in Kobe City, Japan.
AB  - This study, based on a questionnaire survey and workshops, and with a focus on
      the impact of an earthquake on the Nagata Elementary School Community in Kobe
      City, Japan, develops a collaborative model to assess the allocation of residents
      to shelters. The current official allocation plan is compared with three
      alternative allocations developed within the framework of this model. The
      collaborative model identifies accessibility, amenity, capacity, connectivity,
      continuity, security, and stability as the basic, necessary criteria for shelter
      planning. The three alternative allocations are very similar to the local
      residents' own choice of shelters, but they are quite different from the current
      official allocation plan, which is supposed to be followed but has achieved
      relatively low satisfaction among households. The proposed collaborative approach
      provides an effective tool to assess the officially determined allocation plan by
      taking into account the viewpoints of local residents, and the results are useful
      for enhancing community evacuation planning. 

PMID- 24325243
TI  - Organisational resilience following the Darfield earthquake of 2010.
AB  - This paper presents the preliminary findings of a study on the resilience and
      recovery of organisations following the Darfield earthquake in New Zealand on 4
      September 2010. Sampling included organisations proximal and distal to the fault
      trace, organisations located within central business districts, and organisations
      from seven diverse industry sectors. The research captured information on the
      challenges to, the impacts on, and the reflections of the organisations in the
      first months of recovery. Organisations in central business districts and in the
      hospitality sector were most likely to close, while organisations that had
      perishable stock and livestock were more heavily reliant on critical services.
      Staff well-being, cash flow, and customer loss were major concerns for
      organisations across all sectors. For all organisations, the most helpful factors
      in mitigating the effects of the earthquake were their relationship with staff
      members, the design and type of buildings, and critical service continuity or
      swift reinstatement of services. 

PMID- 24325244
TI  - Disasters as an ideological strategy for governing neoliberal urban
      transformation in Turkey: insights from Izmir/Kadifekale.
AB  - Since the turn of the twenty-first century, Turkish cities have undergone large
      scale change through a process referred to as urban transformation, involving,
      notably, the demolition of inner-city low-income settlements. The official
      authorities and business circles have resorted to various forms of discourse to
      justify these projects, which have led to the deportation of a significant number
      of people to peripheral areas. The discourse of 'natural disasters', for example,
      suggests that urban transformation is necessary to protect people from some
      pending event. Probably the most effective application of this discourse has
      occurred in Izmir, where the risk posed by 'landslides' has played a critical
      role in the settlement demolitions conducted in the huge inner-city neighbourhood
      of Kadifekale. By examining the case of Kadifekale, this paper provide some
      insights into how 'natural disasters' serve as a discourse with which to
      legitimise the neoliberal logic entrenched in the urban transformation process in
      Turkey. 

PMID- 24325245
TI  - Classification of residential areas according to physical vulnerability to
      natural hazards: a case study of Canakkale, Turkey.
AB  - The selection of new settlement areas and the construction of safe buildings, as
      well as rendering built-up areas safe, are of great importance in mitigating the
      damage caused by natural disasters. Most cities in Turkey are unprepared for
      natural hazards. In this paper, Canakkale, located in a first-degree seismic zone
      and sprawled around the Sartcay Delta, is examined in terms of its physical
      vulnerability to natural hazards. Residential areas are analysed using GIS
      (geographic information system) and remote-sensing technologies in relation to
      selected indicators. Residential areas of the city are divided into zones
      according to an evaluation of geological characteristics, the built-up area's
      features, and urban infrastructure, and four risk zones are determined. The
      results of the analysis show that the areas of the city suitable for housing are
      very limited. In addition, the historical centre and the housing areas near
      Sartcay stream are shown to be most problematic in terms of natural disasters and
      sustainability. 

PMID- 24325246
TI  - The genus Cyclidiopsis: an obituary.
AB  - Since its creation in 1917 the genus Cyclidiopsis, and its validity, has been a
      source of debate among euglenid taxonomists. While many authors have supported
      its legitimacy, various other authors have considered it to be a subgenus of
      Astasia or even promoted its complete dissolution. In this study, we have
      sequenced the small subunit and large subunit ribosomal DNA of Cyclidiopsis acus,
      the type species for the genus. Subsequent phylogenetic analyses showed that C.
      acus grouped with taxa from the genus Lepocinclis, which necessitated the removal
      of this taxon from Cyclidiopsis and into Lepocinclis as Lepocinclis cyclidiopsis
      nom. nov. After an extensive literature search it was determined that only two
      other previously described Cyclidiopsis taxa were morphologically distinct, and
      the rest were reassigned as synonyms of L. cyclidiopsis. These findings prompted
      a re-examination of the initial description of Cyclidiopsis, and it was
      determined that the morphological characters establishing the genus as a distinct
      group were no longer valid in light of current phylogenetic analyses and the
      emended generic description for Lepocinclis. Therefore, the remaining two taxa
      were formally moved to the genus Lepocinclis as L. crescentia comb. nov. and L.
      pseudomermis comb. nov. 

PMID- 24325248
TI  - Senescence-related genes possibly responsible for poor liver regeneration after
      hepatectomy in elderly patients.
AB  - BACKGROUND AND AIM: Liver regeneration likely decreases with age by an, as yet,
      incompletely understood mechanism, restricting the extent of hepatectomy. We
      therefore analyzed the effect of aging on liver regeneration and investigated
      mechanisms associate with poor regeneration of human liver. METHODS: We assessed
      130 patients who underwent hepatectomy at our institute between 2005 and 2012.
      The patients were divided into two groups, a younger (age < 65 years, n = 59) and
      an older (age > 65 years, n = 71) group. The expression of hepatocyte growth
      factor (HGF), its ligand Met, and the senescence-related genes p16, SIRT1 and
      SMP30 were assessed by qRT-PCR. Simulated preoperative and 1 week and 6 month
      postoperative liver volumes were evaluated in 11 younger and 11 older patients
      using a 3D simulation imaging system. Regenerated liver volumes were calculated
      and compared with clinicopathological factors, and correlations between liver
      regeneration and gene expression were calculated. RESULTS: HGF and Met expression
      was significantly lower, and p16 expression significantly higher in older than in
      younger patients (P < 0.05 each). Mean increases in liver volume after 6 months
      were significantly greater in younger than in older patients (396.5 mL, 45.6% vs
      159.4 mL, 23.3%, P < 0.05) but did not differ significantly at 1 week.
      Furthermore, p16 expression was negatively correlated with liver regeneration in
      older patients (R = -0.67, P < 0.05). CONCLUSION: Poor liver regeneration in
      older patients may be associated with the upregulation of senescence-related
      genes, such as p16, and the downregulation of regeneration-promoting genes, such
      as HGF and Met.

PMID- 24325249
TI  - A single amino acid residue controls ROS production in the respiratory Complex I
      from Escherichia coli.
AB  - Reactive oxygen species (ROS) production by respiratory Complex I from
      Escherichia coli was studied in bacterial membrane fragments and in the isolated
      and purified enzyme, either solubilized or incorporated in proteoliposomes. We
      found that the replacement of a single amino acid residue in close proximity to
      the nicotinamide adenine dinucleotide (NADH)-binding catalytic site (E95 in the
      NuoF subunit) dramatically increases the reactivity of Complex I towards dioxygen
      (O2 ). In the E95Q variant short-chain ubiquinones exhibit strong artificial one
      electron reduction at the catalytic site, also leading to a stronger increase in
      ROS production. Two mechanisms can contribute to the observed kinetic effects:
      (a) a change in the reactivity of flavin mononucleotide (FMN) towards dioxygen at
      the catalytic site, and (b) a change in the population of the ROS-generating
      state. We propose the existence of two (closed and open) states of the NAD(+) 
      bound enzyme as one feature of the substrate-binding site of Complex I. The
      analysis of the kinetic model of ROS production allowed us to propose that the
      population of Complex I with reduced FMN is always low in the wild-type enzyme
      even at low ambient redox potentials, minimizing the rate of reaction with O2 in
      contrast to E95Q variant. 

PMID- 24325250
TI  - Lon protease inactivation, or translocation of the lon gene, potentiate bacterial
      evolution to antibiotic resistance.
AB  - Previous work demonstrated that selection for Escherichia coli mutants with low
      antibiotic resistance frequently resulted in co-selection of lon mutations and
      that lon(-) mutants evolved higher-level resistance faster than a lon(+) strain.
      Here we show that lon mutation causes a very low multidrug resistance by inducing
      the AcrAB-TolC pump via stabilization of the acrAB transcriptional activators
      MarA and SoxS, which are substrates of the Lon protease. Fast evolution of lon(-)
      mutants towards higher resistance involves selection of frequent next-step
      mutations consisting of large duplications including acrAB and the mutated lon
      gene. Resistance results from the combined effects of acrAB duplication and lon
      mutation increasing dosage of efflux pump. In contrast, when acrAB duplication
      occurs as the first step mutation, increased Lon activity caused by lon(+) co
      duplication mitigates the effect of acrAB duplication on resistance, and faster
      evolution towards higher resistance is not observed. As predicted, when the
      functional lon gene is relocated far from acrAB to prevent their co-duplication,
      first-step acrAB duplication confers higher resistance, which then allows
      selection of frequent next-step mutations and results in faster evolution towards
      higher resistance. Our results demonstrate how order of appearance of mutations
      and gene location can influence the rate of resistance evolution. 

PMID- 24325253
TI  - Role of urinary cations in the aetiology of bladder symptoms and interstitial
      cystitis.
AB  - OBJECTIVES: To identify and characterise urinary cationic metabolites, defined as
      toxic factors, in patients with interstitial cystitis (IC) and in control
      subjects. To evaluate the cytotoxicity of the urinary cationic metabolite
      fraction of patients with IC vs control subjects and of individual metabolites in
      cultured urothelial cells. SUBJECTS AND METHODS: Cationic fractions (CFs) were
      isolated from the urine specimens of 62 patients with IC and 33 control subjects
      by solid-phase extraction. CF metabolites were profiled using C18 reverse-phase
      high performance liquid chromatography (RP-HPLC) with UV detection, quantified by
      area-under-the-peaks using known standards, and normalized to creatinine. RP-HPLC
      and liquid chromatography (LC)-mass spectrometry (MS)/tandem MS (MS/MS) were used
      to identify major CF peaks. HTB-4 urothelial cells were used to determine the
      cytotoxicity of CFs and of individual metabolites with and without Tamm-Horsfall
      protein (THP). RESULTS: RP-HPLC analysis showed that metabolite quantity was
      twofold higher in patients with IC compared with control subjects. The mean (SEM)
      for control subjects vs patients was 3.1 (0.2) vs 6.3 (0.5) mAU*min/MUg
      creatinine (P < 0.001). LC-MS identified 20 metabolites. Patients with IC had
      higher levels of modified nucleosides, amino acids and tryptophan derivatives
      compared with control subjects. The CF cytotoxicity was higher for patients with
      IC compared with control subjects. The mean (SEM) for control subjects vs
      patients was -2.3 (2.0)% vs 36.7 (2.7)% (P < 0.001). A total of 17 individual
      metabolites were tested for their cytotoxicity. Cytotoxicity data for major
      metabolites were all significant (P < 0.001): 1-methyladenosine (51%), 5
      methylcytidine (36%), 1-methyl guanine (31%), N(4)-acetylcytidine (24%), N(7)
      methylguanosine (20%) and L-Tryptophan (16%). These metabolites were responsible
      for higher toxicity in patients with IC. The toxicity of all metabolites was
      significantly lower in the presence of control THP (P < 0.001). CONCLUSIONS:
      Major urinary cationic metabolites were characterised and found to be present in
      higher amounts in patients with IC compared with control subjects. The
      cytotoxicity of cationic metabolites in patients with IC was significantly higher
      than in control subjects, and control THP effectively lowered the cytotoxicity of
      these metabolites. These data provide new insights into toxic factor composition
      as well as a framework in which to develop new therapeutic strategies to
      sequester their harmful activity, which may help relieve the bladder symptoms
      associated with IC.

PMID- 24325251
TI  - Interactions of bacterial flagellar chaperone-substrate complexes with FlhA
      contribute to co-ordinating assembly of the flagellar filament.
AB  - Assembly of the bacterial flagellar filament is strictly sequential; the junction
      proteins, FlgK and FlgL, are assembled at the distal end of the hook prior to the
      FliD cap, which supports assembly of as many as 30 000 FliC molecules into the
      filament. Export of these proteins requires assistance of flagellar chaperones:
      FlgN for FlgK and FlgL, FliT for FliD and FliS for FliC. The C-terminal
      cytoplasmic domain of FlhA (FlhAC ), a membrane component of the export
      apparatus, provides a binding-site for these chaperone-substrate complexes but it
      remains unknown how it co-ordinates flagellar protein export. Here, we report
      that the highly conserved hydrophobic dimple of FlhAC is involved in the export
      of FlgK, FlgL, FliD and FliC but not in proteins responsible for the structure
      and assembly of the hook, and that the binding affinity of FlhAC for the
      FlgN/FlgK complex is slightly higher than that for the FliT/FliD complex and
      about 14-fold higher than that for the FliS/FliC complex, leading to the proposal
      that the different binding affinities of FlhAC for these chaperone/substrate
      complexes may confer an advantage for the efficient formation of the junction and
      cap structures at the tip of the hook prior to filament formation. 

PMID- 24325254
TI  - Two-step transpeptidation of the insulin precursor expressed in Pichia pastoris
      to insulin ester via trypsin-catalyzed cleavage and coupling.
AB  - Insulin precursor fusion protein expressed in Pichia pastoris is a single-chain
      protein with a spacer peptide (EEAEAEAEPK) localized at its N-terminal.
      Currently, the one-step transpeptidation reaction with low yield and high cost is
      generally employed to convert the insulin precursor fusion protein into human
      insulin ester. In this study, a two-step transpeptidation reaction was proposed
      separating the cleavage step from the coupling step so that each reaction was
      performed under its optimal conditions. Using this method, the total efficiency
      doubled and the reaction time was shortened compared with the one-step method. In
      addition, the amount of O-t-butyl-l-threonine t-butyl ester and trypsin dosages
      were reduced by 50% and 75%, respectively. This two-step transpeptidation
      strategy was simple and efficient and could be used for the pharmaceutical
      production of human insulin. 

PMID- 24325255
TI  - Implantable nanosensors: toward continuous physiologic monitoring.
AB  - Continuous physiologic monitoring would add greatly to both home and clinical
      medical treatment for chronic conditions. Implantable nanosensors are a promising
      platform for designing continuous monitoring systems. This Feature reviews design
      considerations and current approaches toward such devices. 

PMID- 24325256
TI  - The niche construction perspective: a critical appraisal.
AB  - Niche construction refers to the activities of organisms that bring about changes
      in their environments, many of which are evolutionarily and ecologically
      consequential. Advocates of niche construction theory (NCT) believe that standard
      evolutionary theory fails to recognize the full importance of niche construction,
      and consequently propose a novel view of evolution, in which niche construction
      and its legacy over time (ecological inheritance) are described as evolutionary
      processes, equivalent in importance to natural selection. Here, we subject NCT to
      critical evaluation, in the form of a collaboration between one prominent
      advocate of NCT, and a team of skeptics. We discuss whether niche construction is
      an evolutionary process, whether NCT obscures or clarifies how natural selection
      leads to organismal adaptation, and whether niche construction and natural
      selection are of equivalent explanatory importance. We also consider whether the
      literature that promotes NCT overstates the significance of niche construction,
      whether it is internally coherent, and whether it accurately portrays standard
      evolutionary theory. Our disagreements reflect a wider dispute within
      evolutionary theory over whether the neo-Darwinian synthesis is in need of
      reformulation, as well as different usages of some key terms (e.g., evolutionary
      process). 

PMID- 24325257
TI  - Coexisting orchid species have distinct mycorrhizal communities and display
      strong spatial segregation.
AB  - Because orchids are dependent on mycorrhizal fungi for germination and
      establishment of seedlings, differences in the mycorrhizal communities
      associating with orchids can be expected to mediate the abundance, spatial
      distribution and coexistence of terrestrial orchids in natural communities. We
      assessed the small-scale spatial distribution of seven orchid species co
      occurring in 25 * 25 m plots in two Mediterranean grasslands. In order to
      characterize the mycorrhizal community associating with each orchid species, 454
      pyrosequencing was used. The extent of spatial clustering was assessed using
      techniques of spatial point pattern analysis. The community of mycorrhizal fungi
      consisted mainly of members of the Tulasnellaceae, Thelephoraceae and
      Ceratobasidiaceae, although sporadically members of the Sebacinaceae, Russulaceae
      and Cortinariaceae were observed. Pronounced differences in mycorrhizal
      communities were observed between species, whereas strong clustering and
      significant segregation characterized the spatial distribution of orchid species.
      However, spatial segregation was not significantly related to phylogenetic
      dissimilarity of fungal communities. Our results indicate that co-occurring
      orchid species have distinctive mycorrhizal communities and show strong spatial
      segregation, suggesting that mycorrhizal fungi are important factors driving
      niche partitioning in terrestrial orchids and may therefore contribute to orchid
      coexistence. 

PMID- 24325258
TI  - Two new degradative cassane-type diterpenes isolated from Caesalpinia minax.
AB  - Cassane-type diterpenes are main bioactive constituents of Caesalpinia minax
      HANCE. As a part of our ongoing chemical investigation of C. minax, two new
      degradative cassane-type diterpenes, named caesalpins I (1) and J (2), were
      isolated from the EtOAc extract of the seeds of C. minax. The structures were
      elucidated by means of spectroscopic analysis. 

PMID- 24325259
TI  - The effects of media usage and interpersonal contacts on the stereotyping of
      lesbians and gay men in China.
AB  - Relatively little research has investigated the association of information
      sources and the stereotyping of homosexuals in other cultures. This study is a
      survey of 226 Chinese college students about their stereotypes of homosexuals and
      their sources of information on gays and lesbians. The stereotyping of
      homosexuals is predicted by the size of community, interest in knowing
      homosexuals, and in-person contacts. A higher level of negative stereotypes is
      associated with frequent usage of Chinese media. 

PMID- 24325260
TI  - Vancomycin and daptomycin minimum inhibitory concentration distribution and
      occurrence of heteroresistance among methicillin-resistant Staphylococcus aureus
      blood isolates in Turkey.
AB  - BACKGROUND: The aim of this study was to determine the distribution of vancomycin
      and daptomycin MICs among methicillin-resistant Staphylococcus aureus (MRSA)
      blood isolates, the prevalence of heterogeneous vancomycin-intermediate S. aureus
      (hVISA) and the relationship between hVISA and vancomycin MIC values. METHODS: A
      total of 175 MRSA blood isolates were collected from seven university hospitals
      in Turkey. All isolates were tested for susceptibility to vancomycin and
      daptomycin by reference broth microdilution (BMD) and by standard Etest method.
      BMD test was performed according to CLSI guidelines and Etest was performed
      according to the instructions of the manufacturer. All isolates were screened for
      the presence of the hVISA by using macro Etest (MET) and population analysis
      profile-area under the curve (PAP-AUC) methods. RESULTS: The vancomycin MIC50,
      MIC90 and MIC ranges were 1, 2, and 0.5-2 MUg/ml, respectively, by both of BMD
      and Etest. The daptomycin MIC50, MIC90 and MIC ranges were 0.5, 1 and 0.125 -1
      MUg/ml by BMD and 0.25, 0.5 and 0.06-1 MUg/ml by Etest, respectively. The
      vancomycin MIC for 40.6% (71/175) of the MRSA isolates tested was >1 MUg/ml by
      BMD. No vancomycin and daptomycin resistance was found among MRSA isolates.
      Percent agreement of Etest MICs with BMD MICs within +/-1 doubling dilution was
      100% and 73.1% for vancomycin and daptomycin, respectively. The prevalence of
      hVISA among MRSA blood isolates was 13.7% (24/175) by PAP-AUC method. MET
      identified only 14 of the hVISA strains (sensitivity, 58.3%), and there were 12
      strains identified as hVISA that were not subsequently confirmed by PAP-AUC
      (specificity, 92.1%). CONCLUSIONS: Agreement between BMD and Etest MICs is high
      both for vancomycin and daptomycin. Daptomycin was found to be highly active
      against MRSA isolates including hVISA. A considerable number of isolates are
      determined as hVISA among blood isolates. As it is impractical to use the
      reference method (PAP-AUC) for large numbers of isolates, laboratory methods for
      rapid and accurate identification of hVISA need to be developed.

PMID- 24325261
TI  - Is homeopathy safe? A response to Posadzki et al.

PMID- 24325262
TI  - Acupuncture for military personnel health and performance.

PMID- 24325263
TI  - Dietary patterns and prostate cancer risk: report from the population based ULSAM
      cohort study of Swedish men.
AB  - Dietary pattern analyses have increased the possibilities to detect associations
      between diet and disease. However, studies on dietary pattern and prostate cancer
      are scarce. Food intake data in the Uppsala Longitudinal Study of Adult Men
      cohort was determined by 7-day food records. Adherence to a modified
      Mediterranean Diet Score (mMDS) and a low carbohydrate-high protein (LCHP) score
      were grouped as low, medium, or high in the whole study population (n = 1,044)
      and in those identified as adequate reporters of energy intake (n = 566),
      respectively. Prostate cancer risk was analyzed with Cox proportional hazard
      regression (median follow-up 13 years) and competing risk of death was
      considered. There were no associations between dietary patterns and prostate
      cancer (n = 133) in the whole study population. Among adequate reporters the mMDS
      was not associated with prostate cancer (n = 72). The LCHP score was inversely
      related to prostate cancer in adequate reporters, adjusted hazard ratios; 0.55
      (0.32-0.96) for medium and 0.47 (0.21-1.04) for high compared to low adherent
      participants (P-for-trend 0.04). Risk relations were not attributable to
      competing risk of death. In this study, a LCHP diet was associated with lower
      prostate cancer incidence. Relations emerged in adequate reporters, underscoring
      the importance of high-quality dietary data. 

PMID- 24325264
TI  - Alcohol marketing and drunkenness among students in the Philippines: findings
      from the nationally representative Global School-based Student Health Survey.
AB  - BACKGROUND: A largely unaddressed issue in lower income countries and the
      Philippines, in particular, is the role of alcohol marketing and its potential
      link to early alcohol use among youth. This study examines the associations
      between exposures to alcohol marketing and Filipino youths' drinking prevalence
      and drunkenness. METHODS: Cross-sectional analyses were used to examine the
      Global School-based Student Health Survey (GSHS) conducted in Philippines (2011).
      The self-administered questionnaires were completed by students primarily 13 to
      16 years of age (N = 5,290). Three statistical models were computed to test the
      associations between alcohol marketing and alcohol use, while controlling for
      possible confounding factors. RESULTS: Alcohol marketing, specifically through
      providing free alcohol through a company representative, was associated with
      drunkenness (AOR: 1.84; 95% CI=1.06-3.21) among youths after controlling for
      demographic and psychosocial characteristics, peer environment, and risky
      behaviors. In addition, seeing alcohol ads in newspapers and magazines (AOR:
      1.65, 95% CI=1.05-2.58) and seeing ads at sports events, concerts or fairs (AOR:
      1.50, 95% CI =1.06-2.12) were significantly associated with increased reports of
      drunkenness. CONCLUSIONS: There are significant associations between alcohol
      marketing exposure and increased alcohol use and drunkenness among youth in the
      Philippines. These findings highlight the need to put policies into effect that
      restrict alcohol marketing practices as an important prevention strategy for
      reducing alcohol use and its dire consequences among vulnerable youth.

PMID- 24325266
TI  - A metal-free tandem C-C/C-O bond formation approach to diversely functionalized
      tetrasubstituted furans.
AB  - A novel and efficient method for the synthesis of diversely functionalized furans
      is developed via DBU-mediated tandem Michael addition/5-exo-dig
      cycloisomerization of enynes and keto-methylenes. This [3 + 2]-annulation is
      operationally simple under metal-free reaction conditions with 100% atom economy
      and broad substrate scope. 

PMID- 24325265
TI  - Biotransformation of the high-molecular weight polycyclic aromatic hydrocarbon
      (PAH) benzo[k]fluoranthene by Sphingobium sp. strain KK22 and identification of
      new products of non-alternant PAH biodegradation by liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - A pathway for the biotransformation of the environmental pollutant and high
      molecular weight polycyclic aromatic hydrocarbon (PAH) benzo[k]fluoranthene by a
      soil bacterium was constructed through analyses of results from liquid
      chromatography negative electrospray ionization tandem mass spectrometry (LC/ESI(
      )-MS/MS). Exposure of Sphingobium sp. strain KK22 to benzo[k]fluoranthene
      resulted in transformation to four-, three- and two-aromatic ring products. The
      structurally similar four- and three-ring non-alternant PAHs fluoranthene and
      acenaphthylene were also biotransformed by strain KK22, and LC/ESI(-)-MS/MS
      analyses of these products confirmed the lower biotransformation pathway proposed
      for benzo[k]fluoranthene. In all, seven products from benzo[k]fluoranthene and
      seven products from fluoranthene were revealed and included previously unreported
      products from both PAHs. Benzo[k]fluoranthene biotransformation proceeded through
      ortho-cleavage of 8,9-dihydroxy-benzo[k]fluoranthene to 8-carboxyfluoranthenyl-9
      propenic acid and 9-hydroxy-fluoranthene-8-carboxylic acid, and was followed by
      meta-cleavage to produce 3-(2-formylacenaphthylen-1-yl)-2-hydroxy-prop-2-enoic
      acid. The fluoranthene pathway converged with the benzo[k]fluoranthene pathway
      through detection of the three-ring product, 2-formylacenaphthylene-1-carboxylic
      acid. Production of key downstream metabolites, 1,8-naphthalic anhydride and 1
      naphthoic acid from benzo[k]fluoranthene, fluoranthene and acenaphthylene
      biotransformations provided evidence for a common pathway by strain KK22 for all
      three PAHs through acenaphthoquinone. Quantitative analysis of
      benzo[k]fluoranthene biotransformation by strain KK22 confirmed biodegradation.
      This is the first pathway proposed for the biotransformation of
      benzo[k]fluoranthene by a bacterium.

PMID- 24325267
TI  - Correct dosing of artemether-lumefantrine for management of uncomplicated malaria
      in rural Tanzania: do facility and patient characteristics matter?
AB  - BACKGROUND: Use of artemisinin-based combination therapy (ACT), such as
      artemether-lumefantrine (AL), requires a strict dosing schedule that follows the
      drugs' pharmacokinetic properties. The quality of malaria case management was
      assessed in two areas in rural Tanzania, to ascertain patient characteristics and
      facility-specific factors that influence correct dosing of AL for management of
      uncomplicated malaria. METHODS: Exit interviews were conducted with patients
      attending health facilities for initial illness consultation. Information about
      health workers' training and supervision visits was collected. Health facilities
      were inventoried for capacity and availability of medical products related to
      care of malaria patients. The outcome was correct dosing of AL based on age and
      weight. Logistic regression was used to assess health facility factors and
      patient characteristics associated with correct dosing of AL by age and weight.
      RESULTS: A total of 1,531 patients were interviewed, but 60 pregnant women were
      excluded from the analysis. Only 503 (34.2%) patients who received AL were
      assessed for correct dosing. Most patients who received AL (85.3%) were seen in
      public health facilities, 75.7% in a dispensary and 91.1% in a facility that had
      AL in stock on the survey day. Overall, 92.1% (463) of AL prescriptions were
      correct by age or weight; but 85.7% of patients received correct dosing by weight
      alone and 78.5% received correct dosing by age alone. In multivariate analysis,
      patients in the middle dosing bands in terms of age or weight, had statistically
      significant lower odds of correct AL dosing (p < 0.05) compared to those in the
      lowest age or weight group. Other factors such as health worker supervision and
      training on ACT did not improve the odds of correct AL dosing. CONCLUSION:
      Although malaria treatment guidelines indicate AL dosing can be prescribed based
      on age or weight of the patient, findings from this study show that patients
      within the middle age and weight dosing bands were least likely to receive a
      correct dose by either measure. Clinicians should be made aware of AL dosing
      errors for patients aged three to 12 years and advised to use weight-based
      prescriptions whenever possible.

PMID- 24325268
TI  - A resurgence in field research is essential to better understand the diversity,
      ecology, and evolution of microbial eukaryotes.
AB  - The discovery and characterization of protist communities from diverse
      environments are crucial for understanding the overall evolutionary history of
      life on earth. However, major questions about the diversity, ecology, and
      evolutionary history of protists remain unanswered, notably because data obtained
      from natural protist communities, especially of heterotrophic species, remain
      limited. In this review, we discuss the challenges associated with "field
      protistology", defined here as the exploration, characterization, and
      interpretation of microbial eukaryotic diversity within the context of natural
      environments or field experiments, and provide suggestions to help fill this
      important gap in knowledge. We also argue that increased efforts in field studies
      that combine molecular and microscopical methods offer the most promising path
      toward (1) the discovery of new lineages that expand the tree of eukaryotes; (2)
      the recognition of novel evolutionary patterns and processes; (3) the untangling
      of ecological interactions and functions, and their roles in larger ecosystem
      processes; and (4) the evaluation of protist adaptations to a changing climate. 

PMID- 24325269
TI  - Subconscious manipulation of pain expectation can modulate cortical nociceptive
      processing.
AB  - OBJECTIVE: To determine whether manipulation of the expectation of pain
      inhibition can enhance the efficacy of conditioned pain modulation in healthy
      participants METHODS: A conditioned pain modulation paradigm was used to
      investigate the effect of psychological manipulation of expectation on pain
      inhibition. In 19 healthy men, the lower limb nociceptive flexion reflex was
      elicited in isolation (test stimulus) and during application of 2 forms of
      conditioning stimuli. Following application of the first conditioning stimulus
      (CS1), the participants were informed that the subsequent conditioning stimulus
      (CS2) would elicit a greater amount of inhibition of test pain compared with the
      first. Lower limb flexion reflex size, perceived pain ratings of the test
      stimulus, and ratings of expected pain modulation were obtained for both test and
      conditioning protocols. RESULTS: The inhibition of perceived pain was
      significantly greater with CS2 compared with CS1; however, there was no
      significant difference in inhibition of nociceptive flexion reflex size or the
      participant's reported expectation of pain modulation between the 2 conditioning
      stimuli. DISCUSSION: As perceived pain inhibition was enhanced but flexion reflex
      size unchanged following the intervention, we suggest that the intervention gave
      rise to an inhibition of ascending nociceptive information at a supraspinal level
      resulting in reduced pain perception without influencing spinal level processing
      of nociceptive input. The finding that conditioned pain modulation can be
      enhanced is of relevance to clinical pain populations who commonly show impaired
      inhibition.

PMID- 24325271
TI  - 7,8-dihydroxyflavone ameliorates scopolamine-induced Alzheimer-like pathologic
      dysfunction.
AB  - Scopolamine (Sco) can induce amyloid beta (Abeta) deposition, oxidative stress,
      synaptic dysfunction, and learning/memory impairment as observed in Alzheimer's
      disease (AD), the most common form of dementia affecting more than 25 million
      elderly people worldwide. Herein we explored the protective effect of 7,8
      dihydroxyflavone (7,8-DHF) on Sco-induced Abeta deposition, oxidative stress,
      synaptic dysfunction, and learning/memory defects. Rats were randomly divided
      into four groups (n=12 for each group). The control group received normal saline
      (NS); the Sco group received Sco (1 mg/kg per day) intraperitoneally (i.p.) for 2
      weeks. Mice in the Sco+7,8-DHF group received 1 mg/kg per day 7,8-DHF i.p. for 2
      weeks, followed by Sco (1 mg/kg per day)+1 mg/kg per day 7,8-DHF (i.p.) for
      another 2 weeks. The 7,8-DHF group received 1 mg/kg per day 7,8-DHF (i.p.) for 4
      weeks. Results showed that the supplement of 7,8-DHF significantly reversed Abeta
      deposition, oxidative stress, synaptic dysfunction, and cognitive defects. Our
      data suggest that 7,8-DHF might serve as a promising therapeutic candidate for
      attenuating Sco-induced AD-like pathological dysfuntion.

PMID- 24325272
TI  - Clinical outcomes of a cohort series of patients with hepatocellular carcinoma in
      a hepatitis B virus-endemic area.
AB  - BACKGROUND AND AIMS: To evaluate the clinical outcomes of patients with
      hepatocellular carcinoma (HCC) and compare the findings with that of a previous
      cohort. METHODS: Overall, 1972 HCC patients diagnosed and treated at the National
      Cancer Center, Korea between 2004 and 2009 were enrolled. The data of this cohort
      were compared with those of a previous cohort (2000-2003) from the same
      institution. RESULTS: In all (mean age, 56.4 years; 1642 men), 74.6% was
      hepatitis B virus (HBV) positive, 81.6% were Child-Pugh (CP) class A, and 64.4%
      was Barcelona Clinic Liver Cancer (BCLC) stage C. The modified Union for
      International Cancer Control (mUICC) stage I, II, III, IVa, and IVb was found in
      8.9%, 29.6%, 24.8%, 23.1%, and 13.6% patients, respectively. The most common
      initial treatment was transarterial chemotherapy (58.3%), followed by resection
      (18.6%). The 5-year survival rate of BCLC stage 0, A, B, and C were 79.6%, 67.2%,
      33.9%, and 17.1%, respectively. The performance status, BCLC stage, mUICC stage,
      CP class, model for end-stage liver disease score, tumor characteristics, portal
      vein tumor invasion, and serum alpha-fetoprotein level proved to be independent
      prognostic variables. Overall survival in the present cohort was better than that
      in the previous cohort (hazard ratio, 0.829; 95% confidence interval, 0.754
      0.912), especially for advanced HCC patients with HBV-positive status.
      CONCLUSIONS: This cohort study provides valuable insights into the
      characteristics of HCC in Korean patients. Our findings may help develop clinical
      trials, treatment strategies, and prognosis systems for HCC patients in HBV
      endemic areas.

PMID- 24325273
TI  - Novel nitrocellulose membrane substrate for efficient analysis of circulating
      tumor cells coupled with surface-enhanced Raman scattering imaging.
AB  - The capture and detection of circulating tumor cells (CTCs) in the bloodstream of
      patients with cancer is crucial for the clinical diagnosis and therapy. In the
      present work, a facile and integrated approach based on novel nitrocellulose
      membrane substrate and large-scale surface-enhanced Raman scattering (SERS)
      imaging technology has been developed for CTCs' sensitive detection and
      enumeration. The system mainly consists of three aspects: capture of CTCs in
      bloodstream, SERS probes labeling of the captured CTCs and large-scale SERS
      imaging readout of CTCs enumeration. The NC membrane was used to prepare the
      novel CTC-capture substrate through antibody self-assembled. It was low-cost,
      easily prepared and completely nontoxic. Furthermore, excellent capture
      efficiency of the substrate was demonstrated using nonsmall-cell lung cancer
      (NSCLC) cells (NCI-H1650) as target cells. As the most sensitive detection
      technology, SERS holds huge potential in CTCs analysis. Large-scale SERS imaging
      was employed in CTCs enumeration for the first time, instead of the conventional
      fluorescence imaging. Our SERS probes, with a simplified structure, offered
      highly enough sensitivity to recognize every single cell clearly. In the
      simulation experiment of spiking 100 cancer cells into 1 mL of human whole blood,
      34 cells were captured and counted successfully according to the SERS imaging
      result. Our experimental results demonstrate the potential feasibility of novel
      NC membrane substrate coupled with large-scale SERS imaging technology for the
      accurate enumeration of CTCs in human whole blood. 

PMID- 24325274
TI  - Effects of chronic cochlear electrical stimulation after an extended period of
      profound deafness on primary auditory cortex organization in cats.
AB  - Extended periods of deafness have profound effects on central auditory system
      function and organization. Neonatal deafening results in loss of the normal
      cochleotopic organization of the primary auditory cortex (AI), but
      environmentally-derived intracochlear electrical stimulation, via a cochlear
      implant, initiated shortly after deafening, can prevent this loss. We
      investigated whether such stimulation initiated after an extended period of
      deafness can restore cochleotopy. In two groups of neonatally-deafened cats, a
      multi-channel intracochlear electrode array was implanted at 8 weeks of age. One
      group received only minimal stimulation, associated with brief recordings at 4-6
      week intervals, over the following 6 months to check the efficacy of the implant.
      In the other group, this 6-month period was followed by 6 months of near
      continuous intracochlear electrical stimulation from a modified clinical cochlear
      implant system. We recorded multi-unit clusters in the auditory cortex and used
      two different methods to define the region of interest in the putative AI. There
      was no evidence of cochleotopy in any of the minimally stimulated animals,
      confirming our earlier finding. In three of six chronically stimulated cats there
      was clear evidence of AI cochleotopy, and in a fourth cat in which the majority
      of penetrations were in the anterior auditory field there was clear evidence of
      cochleotopy in that field. The finding that chronic intracochlear electrical
      stimulation after an extended period of deafness is able to restore cochleotopy
      in some (but not all) cases has implications for the performance of patients
      implanted after an extended period of deafness.

PMID- 24325275
TI  - Pathogenicity of two Toxoplasma gondii strains in chickens of different ages
      infected via intraperitoneal injection.
AB  - This experiment was conducted to investigate the pathogenicity of Toxoplasma
      gondii in broilers of different ages. Chickens at the ages of 7, 14, 21 and 28
      days were injected intraperitoneally with 1 * 10(8) tachyzoites of RH and JS
      strains of T. gondii, respectively. The clinical signs and death of chickens were
      recorded daily post inoculation. Serum samples were collected at days 0, 4, 11,
      18, 25, 32, 39, 46 and 53 post infection to screen T. gondii circulating antigens
      (TCA) and T. gondii circulating antibodies (TCAb). The results showed that T.
      gondii infection of 7-day-old chickens caused death, even though the mortality
      rate of the JS strain (100%) was significantly higher than that of the RH strain
      (70%). Chickens at 14 days old showed only mild clinical signs, but no death.
      Neither clinical signs nor death were recorded in 21-day-old and 28-day-old
      chickens. TCA and TCAb became positive at days 4 and 11, respectively. Both the
      TCA and the TCAb of groups 21 days old (RH strain) and 28 days old (both RH and
      JS strains) decreased to a negative level earlier than the other experimental
      groups. Specific T. gondii DNA was detected by polymerase chain reaction in
      chickens that survived in the 7-day-old group (RH strain) and in all infected
      chickens of groups 14 days old and 21 days old injected with both strains. In the
      groups injected at 28 days old, three samples (RH strain) and one sample (JS
      strain) were found negative. The results indicated that the age of the chicken
      was an important factor affecting the pathogenicity of T. gondii and that these
      two strains of T. gondii displayed different virulence for chickens. 

PMID- 24325276
TI  - Multimodal tract-based analysis in ALS patients at 7T: a specific white matter
      profile?
AB  - Our objective was to explore the value of additional MR contrasts in elucidating
      the decrease in fractional anisotropy (FA) as has been observed in the
      corticospinal tracts (CST) of patients with amyotrophic lateral sclerosis (ALS).
      Eleven patients and nine healthy control subjects were scanned at 3T and 7T MRI.
      Whole brain and tract specific comparison was performed of both diffusion
      weighted (3T), quantitative T1 (qT1), magnetization transfer ratio (MTR) and
      amide proton transfer weighted (APTw) imaging (7T). Results of whole brain
      comparison using histogram analyses showed no significant differences between
      patients and controls. Measures along the CST showed a significantly reduced FA
      together with a significantly increased diffusivity perpendicular to the tract
      direction in patients compared to controls. In addition, patients showed a small
      but significant increase in MTR values within the right CST. No significant
      changes were observed in qT1 and APTw values. In conclusion, our findings, based
      on a multimodal approach, revealed that the decrease in FA is most probably
      caused by an increased diffusivity perpendicular to the CST. This diffusivity
      profile, together with the increase in MTR is inconsistent with demyelination but
      consistent with an increase of free liquid spins in the white matter tissue.

PMID- 24325277
TI  - Characterization of the triplet state of tanshinone IIA and its reactivity by
      laser flash photolysis.
AB  - Tanshinone IIA (Tan IIA) has the properties of cardiovascular protection, anti
      inflammation, antioxidation and anticancer. Its light-induced instability has
      drawn our interests in its photochemistry. Therefore, laser flash photolysis
      herein was used to investigate the transient photochemistry of Tan IIA. Our
      results show that direct photoexcitation by 355 nm laser pulses or
      photosensitization by energy transfer can lead to the formation of the triplet
      state of Tan IIA ((3)Tan IIA*). The triplet absorption spectrum and molar
      absorption coefficient, and ISC quantum yield were determined. Self-quenching of
      (3)Tan IIA* by its ground state was identified as an autooxidation reaction.
      (3)Tan IIA* was proved to react quickly with N, N-dimethylaniline, tert
      butylhydroquinone and propyl gallate via electron transfer with the diffusion
      controlled rate constants. One of the products with maximum absorption around 390
      nm was assigned to the radical anion of Tan IIA. Our results indicate that (3)Tan
      IIA* is a reactive transient species and can be generated by photosensitization
      or direct photoexcitation. According to our results, the possible role of Tan IIA
      as a photosensitizer to induce potential phototoxicity via Type-II pathway in the
      presence of O2 can be predicted.

PMID- 24325278
TI  - Bioactive glass BAG-S53P4 for the adjunctive treatment of chronic osteomyelitis
      of the long bones: an in vitro and prospective clinical study.
AB  - BACKGROUND: This study aimed to explore the in vitro antibacterial activity of
      the bioglass BAG S53P4 against multi-resistant microorganisms commonly involved
      in osteomyelitis and to evaluate its use in surgical adjunctive treatment of
      osteomyelitis. METHODS: In vitro antibacterial activity of BAG-S53P4 against
      methicillin resistant Staphylococcus aureus and Staphylococcus epidermidis,
      Pseudomonas aeruginosa and Acinetobacter baumannii isolates was evaluated by
      means of time kill curves, with colony counts performed after 24, 48 and 72 hours
      of incubation. In vivo evaluation was performed by prospectively studying a
      cohort of 27 patients with a clinically and radiologically diagnosed
      osteomyelitis of the long bones in an observational study. Endpoints were the
      absence of infection recurrence/persistence at follow-up, no need for further
      surgery whenever during follow-up and absence of local or systemic side effects
      connected with the BAG use. RESULTS: In vitro tests regarding the antibacterial
      activity of BAG S53P4 showed a marked bactericidal activity after 24 hrs against
      all the tested species. This activity continued in the subsequent 24 hrs and no
      growth was observed for all strains after 72 hrs. Results of the clinical study
      evidenced no signs of infection in 24 patients (88.9%) at the follow-up, while 2
      subjects showed infection recurrence at 6 months from index operation and one
      more needed further surgical procedures. BAG-S53P4 was generally well tolerated.
      CONCLUSIONS: The in vitro and in vivo findings reinforce previous observations on
      the efficacy of BAG-S53P4 for the treatment of chronic osteomyelitis of the long
      bones, also in the presence of multi-resistant strains and in immunocompromised
      hosts, without relevant side effects and without the need for locally adding
      antibiotics. TRIAL REGISTRATION: Deutschen Register Klinischer Studien (DRKS)
      unique identifier: DRKS00005332.

PMID- 24325280
TI  - Stereodivergent synthesis of enantioenriched 4-hydroxy-2-cyclopentenones.
AB  - Protected 4-hydroxycyclopentenones (4-HCPs) constitute an important class of
      intermediates in chemical synthesis. A route to this class of compound has been
      developed. Key steps include Noyori reduction (which establishes the
      stereochemistry of the product), ring-closing metathesis, and simple functional
      group conversions to provide a set of substituted 4-HCPs in either enantiomeric
      form. 

PMID- 24325279
TI  - Did past economic prosperity affect the health related quality of life
      predictors? A longitudinal study on a representative sample of Slovenian family
      medicine patients.
AB  - BACKGROUND: Health related quality of life (HRQOL) as an important measure of
      medical outcomes has been shown to be associated with demographic factors and the
      most common mental and chronic somatic diseases. This study's aim was to identify
      factors predicting changes in HRQOL over a follow-up period in a representative
      sample of Slovenian family medicine patients. METHODS: In a longitudinal multi
      centred study between 2003 and 2005, data were collected from 1118 consecutive
      attendees from 60 family medicine practices in Slovenia on quality of life, socio
      demographic factors and the presence of mental disorders, with follow-up after 6
      and 24 months. Retrospective information on chronic diseases was obtained from
      patients' health records. In three time-sequential multiple linear regression
      models, data on 601 patients (53.8%) was analysed to determine factors associated
      with each component score of quality of life. RESULTS: At baseline the patients
      were 48.58 (SE = 0.58) years of age, over half were women (386 (64.2%)) and most
      were Slovenian (548 (91.2%)). Quality of life was seen to improve over the two
      year period. Factors significantly and consistently associated with a better
      mental component score of quality of life were social support, satisfactory
      circumstances in patients' household and absence of anxiety. Major life events in
      the past year and depression were shown to be risk factors for mental and
      physical components, while level of education, absence of long-term disability
      and chronic pain were identified as predictors of the physical component.
      CONCLUSIONS: Detection and successful treatment of depression and anxiety has a
      potential to lead to improved quality of life in family medicine attendees;
      family physicians should be alert for the early onset of these conditions,
      knowing that symptoms of chronic pain, depression and anxiety often overlap in
      patients. Poorly educated patients and those lacking social support and/or
      satisfactory household circumstances should be recognised and empowered, and
      appropriate coping mechanisms should be introduced.

PMID- 24325281
TI  - Daytime sleepiness in renal transplant recipients is associated with
      immunosuppressive non-adherence: a cross-sectional, multi-center study.
AB  - BACKGROUND: The aims of this study were to determine the prevalence of
      immunosuppressive non-adherence (NA) in renal transplant patients and describe
      whether the degree of daytime sleepiness (DS) and depressive symptomatology are
      associated with immunosuppressive NA. METHODS: Using a cross-sectional design,
      926 home-dwelling renal transplant recipients who were transplanted at one of
      three Swiss transplant centers provided data by self-report. The Basel Assessment
      of Adherence Scale for immunosuppressive was used to measure the following:
      taking, timing, and overall NA to immunosuppressive medication. DS was assessed
      with the Epworth Sleepiness Scale (ESS) (cut-off >=6 for DS) and the Swiss
      Transplant Cohort Study DS item (cut-off >=4 for DS), and depressive
      symptomatology was assessed with the Depression, Anxiety, and Stress Scale (cut
      off>10). An ordinal logistical regression model was applied for statistical
      analysis. RESULTS: The prevalence of the ESS-DS was 51%. NA for taking, timing,
      and the median overall NA level assessed by 0-100% visual analog scale (VAS) was
      16%, 42%, and 0%, respectively. Based on the multivariate analysis, DS was
      significantly associated (p < 0.001) with taking (1.08 [1.04-1.13]), timing (1.07
      [1.03-1.10]), and overall NA (1.09 [1.05-1.13]). Very similar results were found
      for the Swiss Transplant Cohort Study DS item. CONCLUSION: DS is associated with
      immunosuppressive medication NA in renal transplant recipients. Admittedly, the
      association's strength is limited.

PMID- 24325282
TI  - Temperature-density hysteresis in X-ray CT during HIFU thermal ablation: heating
      and cooling phantom study.
AB  - PURPOSE: This paper investigated the effects of thermal ablation treatment on
      imaged X-ray computed tomography (CT) Hounsfield units (HU), for the purpose of
      monitoring tissue denaturation and coagulation. MATERIALS AND METHODS: Eight
      phantoms of water, oil, and chicken serum albumin as well as 15 ex vivo tissue
      samples were heated by applying high intensity focused ultrasound (HIFU) for 10
      to 29 min to obtain denaturation temperatures, (i.e. >50  degrees C). X-ray CT
      scanning was performed simultaneously during heating and post-ablation cooling
      stages, and the HU at the focal zone were registered. The temperature profile
      versus time was also monitored under similar conditions using a thermocouple
      probe. The results were plotted and correlated as curves of HU versus
      temperature. RESULTS: In all specimens studied, HU values depicted an exponential
      curve as a function of temperature during the heating stage. However, linear
      behaviour was observed during the cool-down stage for both chicken serum albumin
      and ex vivo bovine liver. Thus, a hysteresis phenomenon occurred only when the
      thermal conditions induced irreversible changes in the sample with quantification
      demonstrating high correlation with the maximal temperature reached during
      treatment (R(2)> 0.9) for the chicken serum albumin. CONCLUSIONS: Our results
      demonstrate a HU-temperature hysteresis phenomenon for HIFU ablation, which is
      detectible by X-ray CT. This hysteresis is related to the amount of heat induced
      into the tissue and could potentially indicate irreversible tissue damage.
      Accordingly, this measurable phenomenon can be utilised as a quantitative method
      for non-invasive monitoring of thermal ablation.

PMID- 24325283
TI  - Active surveillance for renal angiomyolipoma: outcomes and factors predictive of
      delayed intervention.
AB  - OBJECTIVE: To present the outcomes of active surveillance (AS) for renal
      angiomyolipomas (AMLs) and to assess the clinical features predicting delayed
      intervention of this treatment option. PATIENTS AND METHODS: We retrospectively
      reviewed the outcomes of patients diagnosed with AMLs on computed tomography (CT)
      who were managed with AS at our institution. The AS protocol consisted of 6- and
      12-month, then annual follow-up visits, each one including a physical examination
      and CT imaging. Discontinuation of AS was defined as the need or decision for an
      active procedure during the follow-up period. Causes of delayed intervention, as
      well as the type of active treatment (AT), were recorded. Clinical features at
      presentation of patients failing AS were compared with those who remained under
      AS at the time of the last follow-up. Predictive factors of delayed intervention
      were analysed using univariate and multivariate Cox regression models. RESULTS:
      Overall, 130 patients were included in the analysis, of whom 102 (78.5%) were
      incidentally diagnosed, while 15 (11.5%) and 13 patients (10%) presented with
      flank pain and haematuria, respectively. After a mean (sd) follow-up of 49 (40)
      months, 17 patients (13%) discontinued AS and underwent AT. Patients who
      underwent delayed intervention were more likely to present with a higher body
      mass index, larger tumours and symptomatic disease. Angioembolization represented
      the first-line AT after AS (64.7%), whereas partial nephrectomy was adopted in
      29.4% of patients. On the univariate analysis, risk factors for delayed
      intervention included tumour size >=4 cm, symptoms at diagnosis, and history of
      concomitant or contralateral kidney disease. On the multivariate analysis, only
      tumour size and symptoms remained independently associated with discontinuation
      of AS. CONCLUSIONS: Tumour size and symptoms at initial presentation were highly
      predictive of discontinuation of AS in the management of AMLs. Selective
      angioembolization was the first-line option used for AT after AS was
      discontinued.

PMID- 24325285
TI  - Purification and characterization of polyphenol oxidase from jackfruit (
      Artocarpus heterophyllus ) bulbs.
AB  - Polyphenol oxidase (PPO) from jackfruit bulb was purified through acetone
      precipitation, ion-exchange column, and gel filtration column. PPO was a dimer
      with the molecular weight of 130 kDa determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration. The Km was 8.3
      and 18.2 mM using catechol and 4-methylcatechol as substrates, respectively. The
      optimum pH was 7.0 (catechol as the substrate) or 6.5 (4-methylcatechol as the
      substrate). The optimum temperature was 8  degrees C. The enzyme was stable below
      40  degrees C. The activation energy (Ea) of heat inactivation was estimated to
      be 103.30 kJ/mol. The PPO activity was activated by Mn(2+), SDS, Tween-20, Triton
      X-100, citric acid, and malic acid but inhibited by K(+), Zn(2+), Mg(2+), Ca(2+),
      Ba(2+), cetyl trimethyl ammonium bromide (CTAB), kojic acid, tropolone,
      glutathione (GSH), cysteine (Cys), and ascorbic acid (AA). Cys and AA were
      effective to reduce browning of jackfruit bulbs during the storage at 8  degrees
      C for 15 days. 

PMID- 24325284
TI  - Female promiscuity and maternally dependent offspring growth rates in mammals.
AB  - Conflicts between family members are expected to influence the duration and
      intensity of parental care. In mammals, the majority of this care occurs as
      resource transfer from mothers to offspring during gestation and lactation.
      Mating systems can have a strong influence on the severity of familial conflict-
      where female promiscuity is prevalent, conflict is expected to be higher between
      family members, causing offspring to demand more resources. If offspring are
      capable of manipulating their mothers and receive resources in proportion to
      their demands, resource transfer should increase with elevated promiscuity. We
      tested this prediction, unexplored across mammals, using a comparative approach.
      The total durations of gestation and lactation were not related to testes mass, a
      reliable proxy of female promiscuity across taxa. Offspring growth during
      gestation, however, and weaning mass, were positively correlated with testes
      mass, suggesting that offspring gain resources from their mothers at faster rates
      when familial conflict is greater. During gestation, the relationship between
      offspring growth and testes mass was also related to placenta morphology, with a
      stronger relationship between testes mass and growth observed in species with a
      less invasive placenta. Familial conflict could have a pervasive influence on
      patterns of parental care in mammals.

PMID- 24325287
TI  - Two new ylangene-type sesquiterpenoids from cultures of the fungus Postia sp.
AB  - Two new ylangene-type sesquiterpenoids, postinins A (1) and B (2), were isolated
      from cultures of the fungus Postia sp. Structures 1 and 2 were elucidated on the
      basis of extensive spectroscopic analysis. The bioactivity evaluation showed that
      both compounds had significant inhibitory activities against protein tyrosine
      phosphatase 1B, and SH2-containing cytoplasmic tyrosine phosphatase-1 and -2 with
      IC50 values of 1.6-6.2 MUg/ml.

PMID- 24325286
TI  - Validation of the Coping with Discrimination Scale in sexual minorities.
AB  - The Coping With Discrimination Scale (CDS) shows promise as a self-report measure
      of strategies for coping with racial discrimination. To assess the psychometric
      properties of the measure for use with sexual minorities (i.e., gay, lesbian,
      bisexual, or GLB persons), a nonprobability sample of 371 GLB adults completed
      the instrument along with several standardized, self-report measures.
      Confirmatory factor analyses supported the five-factor structure of the original
      scale with the exclusion of five items. Adequate internal consistency reliability
      was found. Internalization, drug and alcohol use, and detachment subscales were
      correlated positively with measures of psychological distress and negatively with
      a measure of life satisfaction, providing evidence of construct validity. The
      education/advocacy and resistance subscales were largely unrelated to
      concurrently administered validation measures, consistent with prior findings.
      Coping strategy use varied as a function of primary sources of social support.
      The CDS appears to be a psychometrically sound measure of several discrimination
      coping strategies for use with sexual minorities. 

PMID- 24325290
TI  - Counseling for IUDs and implants: are health educators and clinicians on the same
      page?
AB  - CONTEXT: Low knowledge of long-acting reversible contraceptives (LARC) and
      restrictive counseling practices have been documented among contraceptive care
      clinicians. However, little is known about health educators' counseling on LARC,
      how their practices compare with clinicians' and their specific training needs.
      METHODS: A survey conducted in 2011-2012 assessed knowledge and practices related
      to LARC counseling and provision among 410 staff at 40 Planned Parenthood
      clinics. Clinicians' and health educators' knowledge and practices were compared
      via chi-square tests; use of evidence-based criteria was assessed in
      multivariable logistic regression analyses. RESULTS: At least half of both types
      of staff routinely discussed LARC with clients, and nearly all considered the
      methods safe. Health educators considered a smaller proportion of clients
      candidates for LARC than did clinicians (57% vs. 77%), and they were less likely
      to consider IUDs for teenagers (79% vs. 96%), nulliparous women (82% vs. 98%) and
      unmarried clients (90% vs. 99%). In a multivariable model, health educators were
      less likely than clinicians to counsel clients using the least restrictive
      evidence-based criteria (odds ratio, 0.1). Sixty-four percent of health educators
      and 40% of clinicians desired additional LARC training. CONCLUSION: Even in
      clinics that specialize in reproductive health care, health educators are less
      likely than clinicians to apply current evidence-based criteria in counseling
      about LARC. To provide evidence-based contraceptive counseling, health educators
      need training on LARC eligibility and indications.

PMID- 24325293
TI  - Solid state 13C and 2H NMR investigations of paramagnetic [Ni(II)(acac)2L2]
      complexes.
AB  - Nine structurally related paramagnetic acetylacetonato nickel(II) complexes:
      [Ni(acac)2] and trans-[Ni(acac)2(X)2]nH/D2O, X = H2O, D2O, NH3, MeOH, PMePh2,
      PMe2Ph, or [dppe]1/2, n = 0 or 1, dppe = 1,2-bis(diphenylphosphino)ethane, as
      well as cis-[Ni(F6-acac)2(D2O)2], F6-acac = hexafluoroacetylonato, have been
      characterized by solid state (13)C MAS NMR spectroscopy. (2)H MAS NMR was used to
      probe the local hydrogen bonding network in [Ni(acac)2(D2O)2]D2O and cis-[Ni(F6
      acac)2(D2O)2]. The complexes serve to benchmark the paramagnetic shift, which can
      be associated with the resonances of atoms of the coordinated ligands. The
      methine (CH) and methyl (CH3) have characteristic combinations of the isotropic
      shift (delta) and anisotropy parameters (d, eta). The size of the anisotropy (d),
      which is the sum of the chemical shift anisotropy (CSA) and the paramagnetic
      electron-nuclei dipolar coupling, is much more descriptive than the isotropic
      shift. Moreover, the CSA is found to constitute up to one-third of the total
      anisotropy and should be taken into consideration when (13)C anisotropies are
      used for structure determination of paramagnetic materials. The (13)C MAS NMR
      spectra of trans-[Ni(acac)2(PMe2Ph)2], trans-[Ni(acac)2(PMePh2)2], and the
      noncrystallographically characterized trans-[Ni(acac)2(dppe)]n were assigned
      using these correlations. The complexes with L = H2O, D2O, NH3, and MeOH can be
      prepared by a series of solid state desorption and sorption reactions. Crystal
      structures for trans-[Ni(acac)2(NH3)2] and trans-[Ni(acac)2(PMePh2)2] are
      reported. 

PMID- 24325294
TI  - In-hospital costs associated with chronic constipation in Belgium: a
      retrospective database study.
AB  - BACKGROUND: Real-life data on the economic burden of chronic idiopathic
      constipation are scarce. The objectives of this study were to assess
      hospitalization resource use and costs associated with chronic constipation and
      its complications in Belgium. METHODS: This was a single country, retrospective
      study using the IMS Hospital Disease Database (2008), which comprises data on 34%
      of acute hospital beds in Belgium and contains information on patient
      demographics, length of stay (LOS), billed costs, drug use, diagnoses, and
      procedures. Stays with a primary diagnosis of constipation, or a secondary
      diagnosis of constipation and a concomitant diagnosis of a constipation-related
      complication, were selected. Patients with diagnoses of colorectal cancer,
      ulcerative colitis or Crohn's disease, or who had stays involving potentially
      constipation-inducing procedures, were excluded as having secondary constipation.
      Patients receiving opioids, calcium-antagonists, antipsychotics or
      antidepressants were excluded as having drug-induced constipation. KEY RESULTS:
      In total, 1541 eligible patients were identified. The average unadjusted cost per
      day in hospital for idiopathic constipation was ?441 (?311 +/- 1.4 in day clinic
      visits without overnight stays; ?711 +/- 14.0 in full hospitalizations with
      complications). The average LOS in a full hospitalization setting was 7.0 and 4.0
      days in stays with and without complications, respectively. The most frequent
      drug and procedural treatments were osmotically acting laxatives (with
      complications: 42.61%; without complications: 35.69%), and transanal enema (2.32%
      and 2.03%), respectively. CONCLUSIONS & INFERENCES: The burden of constipation is
      often underestimated; it is a condition reflected by hospital-related costs
      comparable to such indications as migraine, which increase when associated with
      complications.

PMID- 24325295
TI  - Endoscopic and clinical analysis of primary T-cell lymphoma of the
      gastrointestinal tract according to pathological subtype.
AB  - BACKGROUND AND AIM: Little is known about the clinicopathological characteristics
      of primary gastrointestinal T-cell lymphomas (PGITL). This study evaluated the
      clinical and endoscopic features of the pathological subtypes of PGITL. METHODS:
      Forty-two lesions in 36 patients with PGITL were assessed, including 15
      enteropathy-associated T-cell lymphomas (EATL), 13 peripheral T-cell lymphomas
      (PTCL), 10 NK/T-cell lymphomas (NK/TL), and four anaplastic large cell lymphomas
      (ALCL). RESULTS: PTCL occurred more frequently in the stomach and duodenum and
      NK/TL more frequently in the small and large intestines (P = 0.009). The
      endoscopic features of the four subtypes were similar (P = 0.124). Fifteen of 41
      lesions (36.6%) were Epstein-Barr virus (EBV) positive, with NK/TL more likely to
      be EBV positive than the other types (P < 0.001). First endoscopy and first
      computed tomography (CT) scan indicated that 65.4% and 51.4% of the lesions,
      respectively, were malignant, and that 43.2% and 42.3%, respectively, were GI
      lymphomas. The two modalities together correctly diagnosed about half of the
      lesions before biopsy. Intestinal perforation was associated with small bowel
      location (P < 0.001) and infiltrative type (P = 0.009), and was more common in
      NK/TL than in the other subtypes (P = 0.015). Multivariate analysis showed that
      higher international prognosis index (P = 0.008) and the presence of
      complications (P = 0.006) were associated with poor prognosis. Survival was
      poorer in patients with small bowel lesions than with lesions at other locations
      (P = 0.048). CONCLUSIONS: The four main pathological types of PGITL differed in
      clinical characteristics. As PGITL was often not diagnosed by initial endoscopic
      or radiological examination, a high index of suspicion is necessary to ensure its
      early diagnosis.

PMID- 24325296
TI  - Numerical study of the influence of water evaporation on radiofrequency ablation.
AB  - BACKGROUND: Radiofrequency ablation is a promising minimal invasive treatment for
      tumor. However, water loss due to evaporation has been a major issue blocking
      further RF energy transmission and correspondently eliminating the therapeutic
      outcome of the treatment. METHOD: A 2D symmetric cylindrical mathematical model
      coupling the transport of the electrical current, heat, and the evaporation
      process in the tissue, has been developed to simulate the treatment process and
      investigate the influence of the excessive evaporation of the water on the
      treatment. RESULTS: Our results show that the largest specific absorption rate
      (QSAR) occurs at the edge of the circular surface of the electrode. When
      excessive evaporation takes place, the water dehydration rate in this region is
      the highest, and after a certain time, the dehydrated tissue blocks the
      electrical energy transmission in the radial direction. It is found that there is
      an interval as long as 65 s between the beginning of the evaporation and the
      increase of the tissue impedance. The model is further used to investigate
      whether purposely terminating the treatment for a while allowing diffusion of the
      liquid water into the evaporated region would help. Results show it has no
      obvious improvement enlarging the treatment volume. Treatment with the cooled-tip
      electrode is also studied. It is found that the cooling conditions of the inside
      agent greatly affect the water loss pattern. When the convection coefficient of
      the cooling agent increases, excessive evaporation will start from near the
      central axis of the tissue cylinder instead of the edge of the electrode, and the
      coagulation volume obviously enlarges before a sudden increase of the impedance.
      It is also found that a higher convection coefficient will extend the treatment
      time. Though the sudden increase of the tissue impedance could be delayed by a
      larger convection coefficient; the rate of the impedance increase is also more
      dramatic compared to the case with smaller convection coefficient. CONCLUSION:
      The mathematical model simulates the water evaporation and diffusion during
      radiofrequency ablation and may be used for better clinical design of
      radiofrequency equipment and treatment protocol planning.

PMID- 24325297
TI  - Smooth muscle-specific drug targets for next-generation drug-eluting stent.
AB  - The occurrence of stent thrombosis is one of the major obstacles limiting the
      long-term clinical efficacy of percutaneous coronary intervention. The anti
      smooth muscle proliferation drugs coated on drug-eluting stents (DES) often
      indistinguishably block re-endothelialization, an essential step toward
      successful vascular repair, due to their nonspecific effect on endothelial cells
      (ECs). Therefore, identification of therapeutic targets that differentially
      regulate vascular smooth muscle cell (VSMC) and EC proliferation may lead to the
      development of ideal drugs for the next-generation DES. Our recent studies have
      shown that CTP synthase 1 (CTPS1) differentially regulates the proliferation of
      VSMC and EC after vascular injury. Therefore, CTPS1 inhibitors are promising
      agents for DES. In addition to CTPS1, other factors have also shown cell-specific
      effects on VSMC and/or EC proliferation and thus may become potential molecular
      targets for developing drugs to coat stents. 

PMID- 24325298
TI  - Measurement of the electrostatic interaction between polyelectrolyte brush
      surfaces by optical tweezers.
AB  - We demonstrated an optical tweezers method to measure the electrostatic
      interaction between the strong polyelectrolyte brushes, poly(2
      (methacryloyloxy)ethyltrimethylammonium chloride) (PMTAC), grafted on silica
      particles in aqueous media. The weak electrostatic interaction was successfully
      detected with a resolution of less than 0.1 MUN m(-1). The apparent Debye length,
      including the charge distribution in the polymer brush and the surface potential,
      decreased as the salt concentration in the medium increased. The experimentally
      obtained surface charge density was much smaller than that estimated from the
      amount of polyelectrolyte on the surface. Furthermore, the dissociation of ionic
      groups was enhanced by decreasing the grafting density of the polyelectrolyte
      brush. The results suggest that the majority of chloride counterions was
      immobilized in the dense polyelectrolyte brush layer to neutralize the high
      charge density. 

PMID- 24325299
TI  - Novel and robust transplantation reveals the acquisition of polarized processes
      by cortical cells derived from mouse and human pluripotent stem cells.
AB  - Current stem cell technologies have enabled the induction of cortical progenitors
      and neurons from embryonic stem cells (ESCs) and induced pluripotent stem cells
      in vitro. To understand the mechanisms underlying the acquisition of apico-basal
      polarity and the formation of processes associated with the stemness of cortical
      cells generated in monolayer culture, here, we developed a novel in utero
      transplantation system based on the moderate dissociation of adherens junctions
      in neuroepithelial tissue. This method enables (1) the incorporation of
      remarkably higher numbers of grafted cells and (2) quantitative morphological
      analyses at single-cell resolution, including time-lapse recording analyses. We
      then grafted cortical progenitors induced from mouse ESCs into the developing
      brain. Importantly, we revealed that the mode of process extension depends on the
      extrinsic apico-basal polarity of the host epithelial tissue, as well as on the
      intrinsic differentiation state of the grafted cells. Further, we successfully
      transplanted cortical progenitors induced from human ESCs, showing that our
      strategy enables investigation of the neurogenesis of human neural progenitors
      within the developing mouse cortex. Specifically, human cortical cells exhibit
      multiple features of radial migration. The robust transplantation method
      established here could be utilized both to uncover the missing gap between
      neurogenesis from ESCs and the tissue environment and as an in vivo model of
      normal and pathological human corticogenesis. 

PMID- 24325300
TI  - A protocol for concurrent high-quality immunohistochemical and biochemical
      analyses in adult mouse central nervous system.
AB  - Biochemical analysis of central nervous system proteins and nucleic acids
      requires fresh-tissue homogenates, whereas immunohistochemistry usually is
      performed in sections prepared from perfusion-fixed tissue. Post-mortem immersion
      fixation is possible, but largely impairs morphological preservation and protein
      antigenicity. Here, we present a simple, fast and versatile protocol allowing
      concurrent biochemical and immunohistochemical analysis, including pre-embedding
      immunoelectron microscopy, using tissue from the same animal. The protocol
      includes a brief transcardiac perfusion with ice-cold, oxygenated and glucose
      supplemented artificial cerebrospinal fluid to maintain brain tissue alive, prior
      to isolation of regions of interest, followed by homogenisation for biochemistry
      or immersion-fixation for immunohistochemistry. We provide several examples
      demonstrating that this protocol allows optimal biochemical and morphological
      analysis, characterised with optimal sensitivity and preservation of tissue
      structure, along with a reduction of artefacts typically seen in perfusion-fixed
      tissue. This protocol should find widespread applications for combining
      analytical methods in tissue from the same animal, thereby reducing the number of
      mice required for a given experiment. 

PMID- 24325301
TI  - Fabrication of free-standing hierarchical carbon nanofiber/graphene
      oxide/polyaniline films for supercapacitors.
AB  - A hierarchical high-performance electrode with nanoacanthine-style polyaniline
      (PANI) deposited onto a carbon nanofiber/graphene oxide (CNF/GO) template was
      successfully prepared via an in situ polymerization process. The morphology
      analysis shows that introducing one-dimensional (1D) CNF could significantly
      decrease/inhibit the staking of laminated GO to form an open-porous CNF/GO
      architecture. Followed with in situ facial deposition of PANI, the as-synthesized
      PANI modified CNF/GO exhibits three-dimensional (3D) hierarchical layered
      nanoarchitecture, which favors the diffusion of the electrolyte ions into the
      inner region of active materials. The hierarchical free-standing electrodes were
      directly fabricated into sandwich structured supercapacitors using 1 M H2SO4 as
      the electrolyte showing a significant specific capacitance of 450.2 F/g at the
      voltage scan rate of 10 mV/s. The electrochemical properties of the hierarchical
      structure can be further improved by a reduction procedure of GO before the
      deposition of PANI. 

PMID- 24325303
TI  - Multimorbidity prevalence in the general population: the role of obesity in
      chronic disease clustering.
AB  - BACKGROUND: The role of obesity in the prevalence and clustering of
      multimorbidity, the occurrence of two or more chronic conditions, is
      understudied. We estimated the prevalence of multimorbidity by obesity status,
      and the interaction of obesity with other predictors of multimorbidity. METHODS:
      Data from adult respondents (18 years and over) to the Health Quality Council of
      Alberta 2012 Patient Experience Survey were analyzed. Multivariable regression
      models were fitted to test for associations. RESULTS: The survey sample included
      4803 respondents; 55.8% were female and the mean age was 47.8 years (SD, 17.1).
      The majority (62.0%) of respondents reported having at least one chronic
      condition. The prevalence of multimorbidity, including obesity, was 36.0% (95%
      CI, 34.8 - 37.3). The prevalence of obesity alone was 28.1% (95% CI 26.6 - 29.5).
      Having obesity was associated with more than double the odds of multimorbidity
      (odds ratio = 2.2, 95% CI 1.9 - 2.7) compared to non-obese. CONCLUSIONS: The
      prevalence of multimorbidity in the general population is high, but even higher
      in obese than non-obese persons. These findings may be relevant for surveillance,
      prevention and management strategies for multimorbidity.

PMID- 24325305
TI  - Does the calcineurin inhibitor have influence on cytomegalovirus infection in
      heart transplantation?
AB  - Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in
      heart transplant (HTx). Our aim was to analyze the rate of CMV infection in HTx
      patients receiving treatment with cyclosporine (CsA) or tacrolimus (Tac). Ninety
      five patients were randomized to receive either CsA (53.7%) or Tac (46.3%). We
      performed prophylaxis with valganciclovir in patients with the highest risk of
      CMV infection. We considered CMV infection as an increased viral load or the
      presence of CMV in histological samples. We analyzed baseline characteristics,
      CMV infection, and other complications. Event-free rates were calculated using
      the Kaplan-Meier method. There were no significant differences in baseline
      characteristics between both groups. CMV infection was detected in 31.6% of
      patients (in 66.7% due to asymptomatic replication). The group treated with Tac
      had a lower rate of CMV infection (15.9% vs. 45.1%, p = 0.002) and longer CMV
      infection-free survival time (1440 vs. 899 d, p = 0.001). No differences were
      observed in the complications analyzed in both groups. The independent risk
      factors for infection identified in the multivariate analysis were treatment with
      CsA and bacterial infections. This was the first study to demonstrate a lower
      rate of CMV infection in patients treated with Tac vs. those treated with CsA
      after HTx. 

PMID- 24325306
TI  - Pollen-mediated gene flow from a commercial potato cultivar to the wild relative
      S. chacoense Bitter under experimental field conditions in Argentina.
AB  - The common potato, Solanum tuberosum ssp. tuberosum (tbr, 2n = 4x = 48; 4EBN),
      has many closely related wild tuber-bearing species. Around 28 to 35 of them
      spontaneously grow in Argentina overlapping, in some areas, with the crop and/or
      experimental transgenic potatoes. Although it is well proven that hybridization
      barriers in potatoes can be incomplete, information on gene flow between
      cultivated and wild germplasm is scarce. Thus, a gene flow field experiment with
      a circular array was set up in Balcarce, Argentina, in 2009, and evaluated over
      two seasons. The tetraploid tbr cultivar Huinkul MAG and one compatible cloned
      genotype of the related wild potato S. chacoense Bitter (chc, 2n = 2x = 24;
      2EBN), which produced 2n eggs, were used, respectively, as pollen donor and
      receptor. Berries with hybrid seeds - as revealed by ploidy and RAPD profiles -
      were obtained in one season, at 30 m from the pollen donor. These results
      reinforce others previously obtained with the same pollen donor and a male
      sterile tbr cultivar in a similar array, pointing out to the need of increasing
      isolation distances in areas of overlap between cultivated and wild potato
      germplasm to prevent or minimize undesirable pollen-mediated gene flow. 

PMID- 24325304
TI  - Circulating dendritic cell precursors in chronic kidney disease: a cross
      sectional study.
AB  - BACKGROUND: Dendritic cells (DC) are professional antigen-presenting cells in the
      immune system. They patrol the blood as circulating dendritic cell precursors
      (DCP). Decreased blood DCP count has been shown to be related to atherosclerotic
      plaque burden. Since chronic kidney disease (CKD) is associated with chronic
      inflammation and increased cardiovascular risk, the aim of our study was to
      investigate a potential effect of CKD on circulating DCP numbers especially in
      patients with a history of cardiovascular disease. METHODS: The number of
      circulating myeloid (mDCP), plasmacytoid (pDCP), and total DCP (tDCP) was
      analysed by flow cytometry in 245 patients with CKD stage 3 (with and without
      known cardiovascular events) and 85 coronary healthy controls. In addition, data
      were compared with a historical group of 130 patients with known coronary artery
      disease (CAD). RESULTS: Compared to controls, patients with CKD 3 revealed a
      significant decrease in circulating mDCP (-29%), pDCP (-43%), and tDCP (-38%) (P
      < 0.001, respectively). Compared with CAD-patients, the decrease in circulating
      DCP in CKD was comparable or even more pronounced indicating a potential role for
      DCP in cardiovascular risk potentiation due to CKD. CONCLUSIONS: Based on
      previous findings in CAD, the marked decrease of DCP in CKD implicates a
      potential role for DCP as a mediator of cardiovascular disease. Whether DCP in
      CKD may act as new cardiovascular biomarkers needs to be established in future
      prospective trials.

PMID- 24325307
TI  - A review of numerical and experimental compensation techniques for skull-induced
      phase aberrations in transcranial focused ultrasound.
AB  - The development of phased array transducers and their integration with magnetic
      resonance (MR) guidance and thermal monitoring has established transcranial MR
      guided focused ultrasound (tcMRgFUS) as an attractive non-invasive modality for
      neurosurgical interventions. The presence of the skull, however, compromises the
      efficiency of transcranial FUS (tcFUS) therapy, as its heterogeneous nature and
      acoustic characteristics induce significant phase aberrations and energy
      attenuation, especially at the higher acoustic frequencies employed in tcFUS
      thermal therapy. These aberrations may distort and shift the acoustic focus as
      well as induce heating at the patient's scalp and skull bone. Phased array
      transducers feature hundreds of elements that can be driven individually, each
      with its own phase and amplitude. This feature allows for compensation of skull
      induced aberrations by calculation and application of appropriate phase and
      amplitude corrections. In this paper, we illustrate the importance of precise
      refocusing and provide a comprehensive review of the wide variety of numerical
      and experimental techniques that have been used to estimate these corrections.

PMID- 24325308
TI  - Molecular and lipid biomarker analysis of a gypsum-hosted endoevaporitic
      microbial community.
AB  - Modern evaporitic microbial ecosystems are important analogs for understanding
      the record of earliest life on Earth. Although mineral-depositing shallow-marine
      environments were prevalent during the Precambrian, few such environments are now
      available today for study. We investigated the molecular and lipid biomarker
      composition of an endoevaporitic gypsarenite microbial mat community in Guerrero
      Negro, Mexico. The 16S ribosomal RNA gene-based phylogenetic analyses of this mat
      corroborate prior observations indicating that characteristic layered microbial
      communities colonize gypsum deposits world-wide despite considerable textural and
      morphological variability. Membrane fatty acid analysis of the surface tan/orange
      and lower green mat crust layers indicated cell densities of 1.6 * 10(9) and 4.2
      * 10(9)  cells cm(-3) , respectively. Several biomarker fatty acids, ?7,10
      hexadecadienoic, iso-heptadecenoic, 10-methylhexadecanoic, and a ?12
      methyloctadecenoic, correlated well with distributions of Euhalothece,
      Stenotrophomonas, Desulfohalobium, and Rhodobacterales, respectively, revealed by
      the phylogenetic analyses. Chlorophyll (Chl) a and cyanobacterial phylotypes were
      present at all depths in the mat. Bacteriochlorophyl (Bchl) a and Bchl c were
      first detected in the oxic-anoxic transition zone and increased with depth. A
      series of monomethylalkanes (MMA), 8-methylhexadecane, 8-methylheptadecane, and 9
      methyloctadecane were present in the surface crust but increased in abundance in
      the lower anoxic layers. The MMA structures are similar to those identified
      previously in cultures of the marine Chloroflexus-like organism 'Candidatus
      Chlorothrix halophila' gen. nov., sp. nov., and may represent the Bchl c
      community. Novel 3-methylhopanoids were identified in cultures of marine purple
      non-sulfur bacteria and serve as a probable biomarker for this group in the lower
      anoxic purple and olive-black layers. Together microbial culture and
      environmental analyses support novel sources for lipid biomarkers in gypsum crust
      mats. 

PMID- 24325309
TI  - Putative domal microbial structures in fluvial siliciclastic facies of the
      Mesoproterozoic (1.09 Ga) Copper Harbor Conglomerate, Upper Peninsula of
      Michigan, USA.
AB  - The Copper Harbor Conglomerate is a Mesoproterozoic (1.09 Ga) freshwater
      sedimentary sequence that outcrops in the Upper Peninsula of Michigan. The
      formation was deposited during infilling of the failed Midcontinent Rift and
      contains fluvial, lacustrine, and alluvial fan facies. This study describes and
      analyzes the formation of small domal structures preserved in fluvial sandstone
      facies within the lower portion of the formation. These domal structures range
      from millimeters to several centimeters in diameter and height, and are preserved
      in convex epirelief on fine-grained sandstone beds. The structures have a
      pustulose texture and a patchy distribution on bedding planes. Slabs containing
      the structures were collected in the field and analyzed in the laboratory through
      inspection of cut slabs, petrographic thin sections, X-radiographs, and RAMAN
      spectroscopy. Results of these analyses reveal that the domal structures often
      contain weak, wavy horizontal bedding and laminae, and lack any vertical
      structures. These results support a biogenic origin of the domal structures
      instead of through abiogenic processes such as loading, sand volcanoes, or
      adhesion warts. These structures are akin to what were traditionally labeled as
      'sand stromatolites', but are now known as 'domal sand structures'. Along with
      previous descriptions of carbonate stromatolites, organic-rich paleosols, and
      microbial sand structures, our findings provide further evidence that mat-forming
      microbial communities thrived in the late Mesoproterozoic freshwater systems of
      the Midcontinent Rift. 

PMID- 24325310
TI  - Evaluation of liquid chromatographic behavior of lumazinic derivatives, from
      alpha-dicarbonyl compounds, in different C18 columns: application to wine samples
      using a fused-core column and fluorescence detection.
AB  - Several C18 columns, packed with totally porous particles of different sizes and
      shell thicknesses, have been compared for simultaneous determination of alpha
      dicarbonyl compounds, previous derivatization to lumazinic derivatives.
      Chromatographic conditions for the separation have been optimized for each
      column, and chromatographic parameters have been calculated and exhaustively
      compared. A core-shell C18 column provided the best results, and a HPLC method
      with fluorimetric detection has been proposed. The developed method has been
      validated in terms of linearity, precision, and sensitivity. Detection and
      quantification limits obtained were comprised between 0.02 and 0.30 and 0.07 and
      1.0 ng mL(-1), respectively, while RSD values obtained were lower than 6% and 5%
      in intraday and interday repeatability studies, respectively. The method has been
      applied to analysis of the alpha-dicarbonyl compounds in different types of
      wines. The higher levels of the total alpha-dicarbonyl compounds were found in
      sweet wines and the lower levels in white wines. 

PMID- 24325311
TI  - Etiology and attitudes: beliefs about the origins of homosexuality and their
      implications for public policy.
AB  - Using survey data from the 2008 election cycle, this article updates and extends
      analysis of public attitudes regarding various aspects of homosexuality.
      Continued expansion of public belief in a biological root to homosexuality is
      found, and variations in such opinions are explored. Public attitudes toward the
      emerging issue of gay adoption is also examined, finding both similarities with
      and important differences from attitudes toward same-sex civil unions, although
      both are profoundly influenced by underlying attitudes regarding the causes of
      homosexuality. 

PMID- 24325312
TI  - Young women's contraceptive microbicide preferences: associations with
      contraceptive behavior and sexual relationship characteristics.
AB  - CONTEXT: In time, microbicides may provide women with dual prevention against
      pregnancy and STDs. Although several microbicide dimensions have been evaluated,
      little is known about women's preferences for contraceptive microbicides and
      correlates of these preferences. METHODS: Acceptability of a hypothetical
      contraceptive microbicide cream or jelly was examined among a -clinic-based
      sample of 266 women in Indianapolis from 2004 (when participants were aged 14-22)
      to 2008. Group conjoint analyses and individual conjoint analyses were used to
      compare preferences with respect to four microbicide -dimensions: contraceptive
      ability, efficacy in relation to condoms, timing of use and texture. Pearson's
      product moment correlations were used to examine the relationship between
      preferences for a contraceptive microbicide and selected characteristics of the
      women. RESULTS: Overall, the top-rated microbicide dimensions were efficacy in
      relation to that of condoms and contraceptive ability (importance scores, 40.0
      and 35.4 out of 100.0, respectively). When all dimension levels were compared,
      contraceptive ability was the most strongly preferred (part-worth utility score,
      8.9), and lower efficacy than that of -condoms was the least strongly preferred (
      11.9). Preference for contraceptive microbicides was positively -associated with
      current contraceptive use, sexual agency, partner communication, commitment to
      avoiding pregnancy and -perceived partner agreement about avoiding pregnancy
      (coefficients, 0.07-0.18). It was negatively associated with current or past
      nonuse of contraceptives, seeking pregnancy and perceived partner agreement about
      seeking -pregnancy (-0.08 to -0.14). CONCLUSIONS: Microbicides with dual
      prevention properties may be attractive to young women. Microbicide development
      and subsequent clinical trials should incorporate contraceptive microbicides.

PMID- 24325313
TI  - Two new isoflavone glycosides from the vine stem of Millettia dielsiana.
AB  - Two new isoflavone glycosides, millesianins F (1) and G (2), along with 11 known
      ones (3-13) have been isolated from the n-butanol extract of the vine stems of
      Millettia dielsiana Harms. The structures of 1 and 2 were established as
      cladrastin 7-O-beta-d-apiofuranosyl-(1 -> 6)-beta-d-glucopyranoside (1) and
      fujikinetin 7-O-beta-d-apiofuranosyl-(1 -> 6)-beta-d-glucopyranoside (2) by means
      of spectroscopic analysis and chemical methods. Some isolates (compounds 1, 3, 4,
      5, 6, and 11) were tested for their effects on the proliferation of hematopoietic
      progenitor cell, and the preliminary results showed that all of investigated
      compounds had moderate activities but not in dose-dependent manners. 

PMID- 24325317
TI  - Self-healing vesicles deposit lipid-coated Janus particles into nanoscopic
      trenches.
AB  - Using dissipative particle dynamics (DPD) simulations, we model the interaction
      between nanoscopic lipid vesicles and Janus nanoparticles localized on an
      adhesive substrate in the presence of an imposed flow. The system is immersed in
      a hydrophilic solution, and the hydrophilic substrate contains nanoscopic
      trenches, which are either step- or wedge-shaped. The fluid-driven vesicle
      successfully picks up Janus particles on the substrate, transports these
      particles as cargo along the surface, and then drops off the particles into the
      trenches. For Janus particles with a relatively large hydrophobic region, lipids
      from the bilayer membrane become detached from the vesicle and bound to the
      hydrophobic domain of the deposited particle. While the detachment of these
      lipids rips the vesicle, it provides a coating that effectively shields the
      hydrophobic portion of the nanoparticle from the outer solution. After the
      particle has been dropped off, the torn vesicle undergoes structural
      rearrangement, reforming into a closed structure that resembles its original
      shape. In effect, the vesicle displays pronounced adaptive behavior, shedding
      lipids to form a protective coating around the particle and undergoing a self
      healing process after the particle has been deposited. This responsive, adaptive
      behavior is observed in cases involving both the step- and wedge-shaped trenches,
      but the step trench is more effective at inducing particle drop off. The results
      reveal that the introduction of grooves or trenches into a hydrophilic surface
      can facilitate the targeted delivery of amphiphilic particles by self-healing
      vesicles, which could be used for successive delivery events. 

PMID- 24325314
TI  - Analysis of the effects of exposure to polychlorinated biphenyls and chlorinated
      pesticides on serum lipid levels in residents of Anniston, Alabama.
AB  - BACKGROUND: Anniston, Alabama, is the site of a former Monsanto plant where
      polychlorinated biphenyls (PCBs) were manufactured from 1929 until 1971.
      Residents of Anniston are known to have elevated levels of PCBs. The objective of
      the study was to test the hypothesis that levels of the various lipid components
      (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) are
      differentially associated with concentrations of total PCBs and total pesticides,
      and further that different congeners, congener groups and different pesticides do
      not have identical associations in serum samples obtained from Anniston residents
      in a cross-sectional study. METHODS: Fasting serum samples were obtained from 575
      residents of Anniston who were not on any lipid-lowering medication and were
      analyzed for 35 PCB congeners, nine chlorinated pesticides, total cholesterol,
      LDL and HDL cholesterol and triglyceride concentrations. Associations between
      toxicant concentrations and lipid levels were determined using multiple linear
      regression analysis. RESULTS: We observed that elevated serum concentrations of
      lipids were associated with elevated serum concentrations of SigmaPCBs and summed
      pesticides in analyses adjusted for age, race, gender, BMI, alcohol consumption,
      smoking and exercising status. The strongest associations were seen for PCB
      congeners with three, four, or at least eight substituted chlorines. Mono-ortho
      substituted congeners 74 and 156, di-ortho congeners 172 and 194, and tri- and
      tetra-ortho congeners 199, 196-203, 206 and 209 each were significantly
      associated with total lipids, total cholesterol and triglycerides. Serum
      concentrations of HCB and chlordane also had strong associations with lipid
      components. CONCLUSIONS: Increased concentrations of PCBs and organochlorine
      pesticides are associated with elevations in total serum lipids, total
      cholesterol and triglycerides, but the patterns are different for different
      groups of PCBs and different pesticides. These observations show selective
      effects of different organochlorines on serum concentrations of different groups
      of lipids. This elevation in concentrations of serum lipids may be the basis for
      the increased incidence of cardiovascular disease found in persons with elevated
      exposures to PCBs and chlorinated pesticides.

PMID- 24325316
TI  - Is knowledge and practice safer in England after the release of national guidance
      on the resuscitation of patients in mental health and learning disabilities?
AB  - ACCESSIBLE SUMMARY: This paper reports on the issue of resuscitation in mental
      health inpatient environments. It reviews the literature on national standards
      and best practice when emergency situations arise in mental health settings. The
      discussion on the best practice literature takes place alongside the reporting of
      a national evaluation of how National Patient Safety Agency improvement
      guidelines for the provision for life support, and resuscitation for mental
      health service users was effectively implemented across health-care providers in
      England. Methods used to establish the effective use of the guidelines include
      feedback from clinical staff and staff responsible for the implementation of the
      new national standards for resuscitation. Serious incident data were also
      compared prior to the release of the national guidelines and after the guideline
      release dates. This included looking at events around choking and
      cardiac/respiratory arrest in inpatient areas. There were five deaths post
      implementation of the guidelines that were considered to have serious enough
      error associated with the resuscitation process. This was down from 18 prior to
      the release of the guidelines. However, our survey showed that despite
      organisations reporting 100% compliance with the implementation of the
      guidelines, around half of frontline clinical staff were not aware of them.
      Although our survey responses show a contradiction between organisational and
      clinical staff awareness, our analysis suggests a reduction in moderate and
      severe harm cases and of deaths. There is evidence of a reduction in the worst
      types of error resulting in death, albeit with small numbers. In 2008, the
      National Patient Safety Agency issued a Rapid Response Report (RRR) aimed at
      health-care organisations providing inpatient care for mental health and learning
      disability patients, requiring organisations to make proper provision for life
      support and resuscitation for these patients. This paper examines whether
      effective implementation of the RRR recommendations had occurred across health
      providers in England. The methods used in this paper are the following: (1)
      Questionnaires were distributed nationally to clinical staff and implementation
      leads; (2) A national comparison of the number and severity of pre- and post-RRR
      release-related incidents involving choking/cardiac/respiratory arrest in Mental
      Health and Learning Disabilities settings was conducted; (3) Organisational
      compliance with the patient safety alert for all National Health Service
      Organisations in England was measured. There were five deaths post-implementation
      of the RRR that were considered to have serious enough error associated with the
      resuscitation. This was down from 18 deaths pre the RRR release. Although our
      survey responses show a contradiction between organisational implementation and
      clinical staff awareness, our analysis suggests a reduction in moderate and
      severe harm cases and of deaths. There is evidence of a reduction in the worst
      types of error resulting in death, albeit with small numbers.

PMID- 24325315
TI  - Impact of postoperative hepatitis B virus reactivation in hepatocellular
      carcinoma patients who formerly had naturally suppressed virus.
AB  - BACKGROUND AND AIM: Hepatitis B virus (HBV) replication detected before the
      resection of hepatocellular carcinoma (HCC) is to be controlled by antiviral
      agents. However, management strategy for patients with preoperatively
      undetectable HBV DNA without antiviral therapy is not clearly delineated. This
      study investigated viral reactivation after the liver resection in non
      replicating HBV DNA-related HCC patients and its impact on the surgical outcome.
      METHODS: From 198 patients that underwent liver resection due to HBV-related HCC,
      101 patients who had serially checked serum HBV DNA were analyzed. RESULTS: From
      101 patients, 33 patients had baseline undetectable HBV DNA. Eleven patients
      (11/33, 33.3%) had viral replication after the liver resection. The postoperative
      viral reactivation (HR: 2.144; 95% CI: 1.122-4.097; P = 0.021), along with the
      existence of satellite nodules (HR: 3.034; 95% CI: 1.1.376-6.689; P = 0.006),
      existence of microvascular invasion (HR: 2.479; 95% CI: 1.303-4.718; P = 0.006),
      and HBeAg positivity (HR: 2.059; 95% CI: 1.155-3.670; P = 0.014) predicted
      recurrence after the surgery. Quantification of intrahepatic total and covalently
      closed circular DNA (cccDNA) was done in 14 patients whose baseline serum HBV DNA
      was undetectable without the use of antiviral agent. Amount of intrahepatic
      cccDNA expressed as copies/hepatocyte in patients with postoperative viral
      reactivation showed significantly higher than those in patients with sustained
      negative serum HBV DNA (P = 0.010). CONCLUSIONS: This study shows that naturally
      suppressed preoperative HBV without application of antiviral agent does not
      ensure undetectable serum HBV after the surgery, and postoperative viral
      reactivation might be associated with HCC recurrence.

PMID- 24325318
TI  - Ruthenium bis-diimine complexes with a chelating thioether ligand: delineating
      1,10-phenanthrolinyl and 2,2'-bipyridyl ligand substituent effects.
AB  - Despite the high pi-acidity of thioether donors, ruthenium(II) complexes with a
      bidentate 1,2-bis(phenylthio)ethane (dpte) ligand and two chelating diimine
      ligands (i.e., Ru(diimine)2(dpte)(2+)) exhibit room-temperature fluid solution
      emission originating from a lowest MLCT excited state (diimine = 2,2'-bipyridine,
      5,5'-dimethyl-2,2'-bipyridine 4,4'-di-tert-butyl-2,2'-bipyridine, 1,10
      phenanthroline, 5-methyl-1,10-phenanthroline, 5-chloro-1,10-phenanthroline, 5
      bromo-1,10-phenanthroline, 5-nitro-1,10-phenanthroline, 4,7-diphenyl-1,10
      phenanthroline, and 3,4,7,8-tetramethyl-1,10-phenanthroline). Crystal structures
      show that the complexes form 2 of the 12 possible conformational/configurational
      isomers, as well as nonstatistical distributions of geometric isomers; there also
      are short intramolecular pi-pi interactions between the diimine ligands and dpte
      phenyl groups. The photoinduced solvolysis product, [Ru(diimine)2(CH3CN)2](PF6)2,
      for one complex in acetonitrile also was characterized by single-crystal X-ray
      diffraction. Variations in the MLCT energies and Ru(III/II) redox couple, E
      degrees '(Ru(3+/2+)), can be understood in terms of the influence of the donor
      properties of the ligands on the mainly metal-based HOMO and mainly diimine
      ligand-based LUMO. E degrees '(Ru(3+/2+)) also is quantitatively described using
      a summative Hammett parameter (sigmaT), as well as using Lever's electrochemical
      parameters (EL). Recommended parametrizations for substituted 2,2'-bipyridyl and
      1,10-phenanthrolinyl ligands were derived from analysis of correlations of E
      degrees '(Ru(3+/2+)) for 99 homo- and heteroleptic ruthenium(II) tris-diimine
      complexes. This analysis reveals that variations in E degrees '(Ru(3+/2+)) due to
      substituents at the 4- and 4'-positions of bipyridyl ligands and 4- and 7
      positions of phenanthrolinyl ligands are significantly more strongly correlated
      with sigmap(+) than either sigmam or sigmap. Substituents at the 5- and 6
      positions of phenanthrolinyl ligands are best described by sigmam and have
      effects comparable to those of substituents at the 3- and 8-positions.
      Correlations of EL with sigmaT for 1,10-phenanthrolinyl and 2,2'-bipyridyl
      ligands show similar results, except that sigmap and sigmap(+) are almost equally
      effective in describing the influence of substituents at the 4- and 4'-positions
      of bipyridyl ligands. MLCT energies and d(5)/d(6)-electron redox couples of the
      complexes with 5-substituted 1,10-phenanthroline exhibit correlations with values
      for other d(6)-electron metal complexes that can be rationalized in terms of the
      relative number of diimine ligands and substituents. 

PMID- 24325320
TI  - Fibrinolytic therapy in patients with ST-elevation myocardial infarction.
AB  - ST-elevation myocardial infarction (STEMI) is related to acute occlusion of a
      coronary artery by a fibrin-rich thrombus. Early reperfusion in STEMI reduces
      infarct size and improves prognosis. Acute reperfusion may be achieved with
      percutaneous coronary intervention (PCI) and/or fibrinolytic agents. When
      performed in a timely manner, primary PCI is the preferred method of reperfusion;
      however, due to logistic reasons, including lack of PCI-capable hospitals and
      delay in the first medical contact-to-balloon time, this simplified approach
      lacks universal applicability. Due to clinical efficacy and the ease of
      administration, fibrinolysis is still an important reperfusion modality in
      patients with STEMI who cannot have primary PCI within guideline-recommended
      time. This review focuses on the role of fibrinolysis in patients with STEMI. 

PMID- 24325319
TI  - The polycomb protein Ezh2 impacts on induced pluripotent stem cell generation.
AB  - Reprogramming of somatic cells toward pluripotency involves extensive chromatin
      reorganization and changes in gene expression. Polycomb group (PcG) proteins are
      key regulators of chromatin structure, cell identity, and development. In this
      study, we investigated the impact of Ezh2, a core subunit of Polycomb repressive
      complex 2 (PRC2), on the generation of induced pluripotent stem (iPS) cells. We
      found that Ezh2 expression is induced during iPS cell generation and iPS cells
      contain high levels of Ezh2 mRNA and protein. Importantly, shRNA knockdown of
      Ezh2 during reprogramming severely impairs iPS cell generation. Mechanistically,
      Ezh2 acts during reprogramming at least in part through repressing the Ink4a/Arf
      locus, which represents a major roadblock for iPS cell generation. Interestingly,
      knockdown of Ezh2 in established pluripotent cells leaves pluripotency and self
      renewal of embryonic stem cells and iPS cells unaffected. Altogether, our results
      demonstrate that Ezh2 is critical for efficient iPS cell generation, whereas it
      is dispensable for maintaining the reprogrammed iPS cell state. 

PMID- 24325321
TI  - Effects of intracerebroventricular infusion of somatostatin-14 on peripheral
      glucoregulation in dogs.
AB  - Somatostatin (SST) is an inhibitory hormone that regulates numerous biological
      processes and circulates in two bioactive isoforms: SST-14 and SST-28. SST-14 is
      the predominant form in the hypothalamus and regulates the secretion of growth
      hormone (GH) (directly) and of thyroid-stimulating hormone (indirectly). In the
      periphery, SST is a potent inhibitor of glucagon and insulin secretion. In the
      present study, we aimed to investigate the effect of i.c.v. administration of SST
      14 on glucose metabolism. Twenty healthy adult dogs randomly received either a
      bolus i.c.v. infusion of 5, 25 or 50 MUg of SST-14 or an equivalent amount of
      artificial cerebrospinal fluid through an epicranial apparatus during fasting.
      The same experiment was repeated during concomitant intraduodenal infusion of
      glucose solution through a Mann-Bollman fistula. Serum levels of glucose, insulin
      and glucose-dependent insulinotrophic peptide (GIP), plasma SST and serum GH
      levels were assayed. Circulating levels of SST and GH did not change
      significantly during i.c.v. infusions. Bolus infusion of 50 MUg of SST-14
      produced an increase in serum glucose levels at 10 min (94 +/- 2.5 mg/dl at
      baseline versus 101 +/- 3 mg/dl, P = 0.04) and significantly suppressed insulin
      levels, reaching maximal suppression at 60 min after infusion (9 +/- 1.3 MUIU/ml
      at baseline versus 4.6 +/- 0.5 MUIU/ml P = 0.04) in fasting animals. Similar
      results were obtained during intraduodenal infusion of glucose through a Mann
      Bollman fistula. GIP levels did not change significantly during i.c.v.
      administration of SST-14. Intracerebroventricular infusion of SST-14 increases
      glucose and suppresses insulin levels in the periphery independently of
      circulating SST levels.

PMID- 24325322
TI  - Li storage and impedance spectroscopy studies on Co3O4, CoO, and CoN for Li-ion
      batteries.
AB  - The compounds, CoN, CoO, and Co3O4 were prepared in the form of nano
      rod/particles and we investigated the Li-cycling properties, and their use as an
      anode material. The urea combustion method, nitridation, and carbothermal
      reduction methods were adopted to prepare Co3O4, CoN, and CoO, respectively. X
      ray diffraction (XRD), scanning electron microscope (SEM), transmission electron
      microscope (TEM), and the Brunauer-Emmett-Teller (BET) surface and density
      methods were used to characterise the materials. Cyclic voltammetry (CV) was
      performed and galvanostatic cycling tests were also conducted up to 60-70 cycles.
      The observed reversible capacity of all compounds is of the increasing order CoO,
      Co3O4, CoN and all compounds showed negligible capacity fading. CoO allows for
      Li2O and Co metal to form during the discharge cycle, allowing for a high
      theoretical capacity of 715 mA h g(-1). Co3O4 allows for 4 Li2O and 3Co to form,
      and has a theoretical capacity of 890 mAhg(-1). CoN is the best anode material of
      the three because the nitrogen allows for Li3N and Co to form, resulting in an
      even higher theoretical capacity of 1100 mAhg(-1) due to the Li3N and Co metal
      formation. Irrespective of morphology the charge profiles of all three compounds
      showed a major plateaux ~2.0 V vs. Li and potential values are almost unchanged
      irrespective of crystal structure. Electrochemical impedance spectroscopy (EIS)
      was performed to understand variation resistance and capacitance values.

PMID- 24325323
TI  - Changes in the composition and diversity of the bacterial microbiota associated
      with oysters (Crassostrea corteziensis, Crassostrea gigas and Crassostrea
      sikamea) during commercial production.
AB  - The resident microbiota of three oyster species (Crassostrea corteziensis,
      Crassostrea gigas and Crassostrea sikamea) was characterised using a high
      throughput sequencing approach (pyrosequencing) that was based on the V3-V5
      regions of the 16S rRNA gene. We analysed the changes in the bacterial community
      beginning with the postlarvae produced in a hatchery, which were later planted at
      two grow-out cultivation sites until they reached the adult stage. DNA samples
      from the oysters were amplified, and 31 008 sequences belonging to 13 phyla
      (including Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes) and 243
      genera were generated. Considering all life stages, Proteobacteria was the most
      abundant phylum, but it showed variations at the genus level between the
      postlarvae and the adult oysters. Bacteroidetes was the second most common
      phylum, but it was found in higher abundance in the postlarvae than in adults.
      The relative abundance showed that the microbiota that was associated with the
      postlarvae and adults differed substantially, and higher diversity and richness
      were evident in the postlarvae in comparison with adults of the same species. The
      site of rearing influenced the bacterial community composition of C. corteziensis
      and C. sikamea adults. The bacterial groups that were found in these oysters were
      complex and metabolically versatile, making it difficult to understand the host
      bacteria symbiotic relationships; therefore, the physiological and ecological
      significances of the resident microbiota remain uncertain.

PMID- 24325325
TI  - Investigating the experiences in a school-based occupational therapy program to
      inform community-based paediatric occupational therapy practice.
AB  - BACKGROUND/AIM: A collaborative approach with teachers is required when providing
      community-based occupational therapy to educationally at risk children.
      Collaborators share common goals and interact and support each other but
      challenges arise in providing collaborative occupational therapy in settings
      outside the school environment. The aim of this study was to capture experiences
      of teachers and occupational therapists working within a school-based
      occupational therapy program to determine if their experiences could inform
      collaborative practice. METHOD: In this pilot study, participant responses to
      questionnaires (n = 32) about their experiences formed the basis for focus groups
      and individual interviews. Two focus group were conducted, one with teachers (n =
      11) and one with occupational therapy participants (n = 6). Individual interviews
      were conducted with the supervising occupational therapist, school principal and
      two leading teachers. Descriptive statistics were used to analyse the data from
      closed questions, and thematic analysis using a constant comparison approach was
      used to analyse open ended questions, focus groups and interviews. RESULTS: Three
      main themes emerged: (i) the need for occupational therapists to spend time in
      the school, to explain their role, build relationships, understand classroom
      routines and the teacher role; (ii) occupational therapists need to not see
      themselves as the expert but develop equal partnerships to set collaborative
      goals and (iii) occupational therapists advocating for all parties to be informed
      throughout the occupational therapy process. CONCLUSION: The pilot study findings
      identified teacher and therapist experiences within the school setting that could
      inform improved collaborative practice with teachers and community-based
      occupational therapists and these findings warrant further investigation.

PMID- 24325327
TI  - Supplementary biotin decreases tibial bone weight, density and strength in
      riboflavin-deficient starter diets for turkey poults.
AB  - 1. Growth and skeletal responses to different dietary concentrations of
      riboflavin and biotin were compared in turkey poults from hatch to 21 d of age.
      The birds were fed on a turkey starter diet with different concentrations of
      supplementary riboflavin (0, 20 and 40 mg/kg) and biotin (0, 0.3 and 0.6 mg/kg)
      in a factorial design. 2. Poults fed on diets with no supplementary riboflavin
      had poor gait scores, decreased times to sit and higher rates of culling compared
      to poults fed on the control diet (20 mg riboflavin and 0.3 mg biotin/kg
      [corrected] diet). Histologically, riboflavin deficiency was associated with a
      peripheral neuropathy similar to that described previously in chicks and,
      unexpectedly, in growth plate abnormalities. 3. Tibiae of poults fed on the
      control diet were larger, more dense, stronger and stiffer than the diets with no
      supplementary riboflavin. 4. Increasing supplementary biotin in poults fed on
      diets with no supplementary riboflavin was associated with a decrease in tibia
      weight, density, strength and stiffness. 5. The results demonstrated that
      riboflavin deficiency in fast-growing turkey poults was associated with growth
      retardation, growth plate disturbance and peripheral nerve dysfunction leading to
      an inability to walk.

PMID- 24325326
TI  - The role of at-risk alcohol/drug use and treatment in appointment attendance and
      virologic suppression among HIV(+) African Americans.
AB  - The causes of poor clinic attendance and incomplete virologic suppression among
      HIV(+) African Americans (AAs) are not well understood. We estimated the effect
      of at-risk alcohol/drug use and associated treatment on attending scheduled
      appointments and virologic suppression among 576 HIV(+) AA patients in the
      University of Alabama at Birmingham (UAB) 1917 Clinic Cohort who contributed 591
      interviews to the analysis. At interview, 78% of patients were new to HIV care at
      UAB, 38% engaged in at-risk alcohol/drug use or received associated treatment in
      the prior year, while the median (quartiles) age and CD4 count were 36 (28; 46)
      years and 321 (142; 530) cells/MUl, respectively. In the 2 years after an
      interview, half of the patients had attended at least 82% of appointments while
      half had achieved virologic suppression for at least 71% of RNA assessments.
      Compared to patients who did not use or receive treatment, the adjusted risk
      ratio (aRR) for attending appointments for patients who did use but did not
      receive treatment was 0.97 (95% confidence limits: 0.92, 1.03). The corresponding
      aRR for virologic suppression was 0.94 (0.86, 1.03). Compared to patients who did
      not receive treatment but did use, the aRR for attending appointments for
      patients who did receive treatment and did use was 0.86 (0.78, 0.95). The
      corresponding aRR for virologic suppression was 1.07 (0.92, 1.24). Use was
      negatively associated with attendance and virologic suppression among patients
      not in treatment. Among users, treatment was negatively associated with
      attendance yet positively associated with virologic suppression. However, aRR
      estimates were imprecise.

PMID- 24325329
TI  - Living tensions: reconstructing notions of professionalism in occupational
      therapy.
AB  - BACKGROUND/AIM: Reform of health organisations has brought significant changes to
      healthcare systems with attendant consequences for the definition and practice of
      professionalism. Occupational therapists must continually strive to provide
      excellent patient care, delivering positive patient outcomes whilst responding
      effectively to increasing fiscal constraint and changing organisational
      paradigms. This paper explores the experiences of occupational therapists as they
      reconstruct professionalism as a consequence of health care reform in England.
      METHOD: Fourteen occupational therapists were interviewed over 12 months across
      five National Health Service organisations in England. Each participant was
      interviewed three times and was asked to keep a monthly diary of critical
      incidents. A process of narrative analysis was developed to analyse these data.
      RESULTS: Findings suggest that changes have occurred in the National Health
      Service which affects notions of professional values, expertise, status and
      accountability. However, far from seeing themselves as mere responders to
      stimuli, occupational therapists tell of mediating policies, of responding,
      experimenting and redefining choices whilst struggling to reconstruct
      professionalism. CONCLUSIONS: It is suggested that professionalism can be
      conceived as a reflexive ethical concept in that it is through the process of
      reflecting on the discursive and behavioural options and values available that
      occupational therapists come to understand, and define their professional selves.

PMID- 24325328
TI  - Mapping and exploring health systems' response to intimate partner violence in
      Spain.
AB  - BACKGROUND: For a comprehensive health sector response to intimate partner
      violence (IPV), interventions should target individual and health facility
      levels, along with the broader health systems level which includes issues of
      governance, financing, planning, service delivery, monitoring and evaluation, and
      demand generation. This study aims to map and explore the integration of IPV
      response in the Spanish national health system. METHODS: Information was
      collected on five key areas based on WHO recommendations: policy environment,
      protocols, training, monitoring and prevention. A systematic review of public
      documents was conducted to assess 39 indicators in each of Spain's 17 regional
      health systems. In addition, we performed qualitative content analysis of 26
      individual interviews with key informants responsible for coordinating the health
      sector response to IPV in Spain. RESULTS: In 88% of the 17 autonomous regions,
      the laws concerning IPV included the health sector response, but the integration
      of IPV in regional health plans was just 41%. Despite the existence of a
      supportive national structure, responding to IPV still relies strongly on the
      will of health professionals. All seventeen regions had published comprehensive
      protocols to guide the health sector response to IPV, but participants recognized
      that responding to IPV was more complex than merely following the steps of a
      protocol. Published training plans existed in 43% of the regional health systems,
      but none had institutionalized IPV training in medical and nursing schools. Only
      12% of regional health systems collected information on the quality of the IPV
      response, and there are many limitations to collecting information on IPV within
      health services, for example underreporting, fears about confidentiality, and
      underuse of data for monitoring purposes. Finally, preventive activities that
      were considered essential were not institutionalized anywhere. CONCLUSIONS:
      Within the Spanish health system, differences exist in terms of achievements both
      between regions and between the areas assessed. Progress towards integration of
      IPV has been notable at the level of policy, less outstanding regarding health
      service delivery, and very limited in terms of preventive actions.

PMID- 24325330
TI  - Being who I am: effective teaching, learning, student support, and societal
      change through LGBQ faculty freedom.
AB  - Framed within the context of a heterosexist society in which not all sexual
      minority faculty feel professionally and/or personally safe stepping out of the
      classroom closet, this qualitative study examines the phenomenon of non
      heterosexual faculty disclosing their sexual orientation to students in their
      classrooms. Findings demonstrate the depth and magnitude of impact the disclosure
      has on teaching, learning, student support, and societal change. Overarching is
      that faculty do not necessarily view the experience as "coming out in the
      classroom," but rather as "being who I am" in terms of freedom to present an
      authentic self, if so desired, to students. 

PMID- 24325331
TI  - Seroprevalence of herpes virus associated with the presence and severity of oral
      mucositis in children diagnosed with acute lymphoid leukemia.
AB  - INTRODUCTION: Acute lymphoid leukemia (ALL) is the hematologic neoplasia most
      commonly diagnosed in children. Among the secondary side effects of chemotherapy,
      mucositis is the most frequent complication. The aim of this study was to
      evaluate the seroprevalence of herpes viruses HSV-1, EBV, and CMV and the
      presence and severity of oral mucositis in children and adolescents diagnosed
      with ALL. METHODOLOGY: Ninety-two patients diagnosed with ALL were evaluated.
      Serum samples were collected before chemotherapy and tested by ELISA method.
      Presence of mucositis was observed on the first day before antineoplastic therapy
      (D0) and on 7th day post-therapy (D7). Classification of mucositis intensity was
      performed according to toxicity criteria established by the National Cancer
      Institute. RESULTS: 70.7% of the patients presented mucositis on the D7, and of
      these, 60% were classified as Grade I and 40% as Grade II; of the 92 individuals
      tested, 59 (64.1%) presented antibodies for HSV-1, 57 (62%) for EBV, 75 (81.5%)
      for CMV_IgG, and 21 (22.8%) for CMV_IgM. Using a logistic regression model, the
      presence of HSV-1 was observed to be 4.10 times greater in Grade II mucositis
      severity than in Grade I (P = 0.03). CONCLUSION: Based on the findings of this
      study, it was possible to conclude that infection by the herpes viruses HSV-1,
      EBV, and CMV is ubiquitous in the studied population and that HSV-1 may be a risk
      factor for aggravating the severity of mucositis.

PMID- 24325332
TI  - Guillain-Barre syndrome as a cause of acute flaccid paralysis in Iraqi children:
      a result of 15 years of nation-wide study.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is the most common cause of acute
      flaccid paralysis (AFP) in the post-poliomyelitis eradication era. This is the
      first study done to identify the epidemiology, clinical features, and outcome of
      GBS in Iraqi children over 15 years. METHODS: The surveillance database about AFP
      cases < 15 years reported during January 1997-December 2011 was used. RESULTS:
      GBS represented 52.5% of AFP cases, with an incidence of 1.33 case/100,000
      population < 15 years/year. There was a higher incidence in the Southern
      provinces, age group 1-4 years, males, and outside the capital city of province,
      with no significant seasonal variations (p = .22). Survival probability after the
      1 year of onset for those with respiratory muscle involvement was .76 (95% CI:
      .60-.86), versus .97 (95% Cl: .96-.98) for those who did not develop it (p <
      .001); and .97 (95% CI: .96-.98) for those living inside the capital city, versus
      .94 (.93-.95) for those living outside (p = .001). Cumulative incidence of
      residual paralysis for patients living inside the capital city was .21 (95% CI:
      .18-.24), versus .27 (95% CI: .25-.29) for those living outside (p < .001).
      CONCLUSIONS: The incidence, age and gender distribution, and seasonality of GBS
      among Iraqi children is similar to those reported from other previous studies. It
      is the most important cause of AFP, especially in those between the age of 1 to 4
      years living in rural areas.

PMID- 24325333
TI  - Crossed molecular beams studies of phenyl radical reactions with propene and
      trans-2-butene.
AB  - The reactions of phenyl radicals with propene have been studied at collision
      energies of 84 and 108 kJ/mol using the crossed molecular beams technique. The
      branching ratios between methyl radical elimination forming C8H8 and H-atom
      elimination forming C9H10 were found to be 10 +/- 1:1 at 84 kJ/mol and 3 +/- 1:1
      at 108 kJ/mol. By using "soft" 9.9 eV vacuum ultraviolet photoionization for
      product detection, we were able to observe both product channels with negligible
      fragmentation of C9H10 to C8H8(+). Our finding that CH3 elimination is dominant
      is consistent with conclusions from a recent study employing a pyrolysis
      molecular beam reactor using photoionization detection. However, our C8H8/C9H10
      branching ratios are significantly larger than inferred from previous CMB
      experiments and RRKM calculations. For comparison, we have also studied the
      reactions of phenyl radicals with trans-2-butene at Ecoll = 97 kJ/mol. In this
      case, the symmetry of trans-2-butene makes both alkene addition sites chemically
      equivalent. The intermediate formed in the reaction with trans-2-butene is
      similar to the 2-carbon addition intermediate in the reaction with propene. We
      observed only methyl elimination in the reaction with trans-2-butene, with no
      evidence for H-atom elimination, consistent with conclusions that C-C bond
      fission is the most favorable channel in these systems. Analogies between phenyl
      radical reactions with propene and trans-2-butene are used to provide insight
      into the mechanisms in the propene reaction. 

PMID- 24325334
TI  - Predominant association of Raoultella bacteremia with diseases of the biliary
      tract.
AB  - A case series of 14 patients with Raoultella bacteremia was compared with 28
      Klebsiella oxytoca and 28 Klebsiella pneumoniae bacteremia cases. Forty-three
      percent of Raoultella bacteremia cases were associated with biliary tract
      disease, compared to 32% and 22% of patients with K. oxytoca and K. pneumoniae
      bacteremia, respectively.

PMID- 24325335
TI  - Incidence and risk factors for carbapenem- and multidrug-resistant Acinetobacter
      baumannii bacteremia in hematopoietic stem cell transplantation recipients.
AB  - BACKGROUND: Bacteremia with multidrug-resistant (MDR) Acinetobacter baumannii
      with carbapenem resistance is an important healthcare-associated infection that
      increases morbidity and mortality in immunocompromised patients. The aim of this
      study was to assess the annual incidence and clinical characteristics of such
      bacteremia and to identify the risk factors for infection in hematopoietic stem
      cell transplantation (HSCT) recipients. METHODS: A retrospective cohort and case
      control study was conducted in 483 HSCT recipients between January 2005 and
      December 2011 at a single tertiary center. Thirty-eight control HSCT patients
      without evidence of post-transplant infection were matched with 19 patients with
      bacteremia due to MDR A. baumannii in a 2:1 ratio. RESULTS: The total incidence
      of carbapenem-resistant-MDR A. baumannii bacteremia was 0.52 cases/10,000 patient
      days. In most cases (17 of 19, 89.5%), bacteremia developed after engraftment.
      Pneumonia was the origin of bacteremia in all patients. Eighteen (94.7%) patients
      with bacteremia and 3 (8.3%) without bacteremia died. In multivariate regression
      analyses, the duration between admission and HSCT (odds ratio (OR) 2.19 per 1-day
      increase, p = 0.030) and a history of care in an intensive care unit after HSCT
      (OR 32.2, p = 0.021) were independent risk factors for the development of
      carbapenem-resistant-MDR A. baumannii bacteremia. CONCLUSIONS: We report that
      carbapenem-resistant-MDR A. baumannii bacteremia in HSCT recipients is a fatal
      infectious complication and mainly develops after engraftment.

PMID- 24325336
TI  - Skin and soft tissue infection caused by Achromobacter xylosoxidans: report of 14
      cases.
AB  - BACKGROUND: Skin and soft tissue infections (SSTIs) caused by Achromobacter
      xylosoxidans are very infrequent. The aim of the present study was to investigate
      the clinical and microbiological characteristics of this infection. METHODS: We
      carried out a retrospective review of 14 cases of SSTI due to A. xylosoxidans
      that occurred at the University Hospital of Guadalajara (Spain) from January 2007
      to December 2012. RESULTS: The infection was secondary to vascular diseases,
      trauma, and recent surgery in 12 patients (85.7%). The most frequent clinical
      presentation was infection of a vascular ulcer (5 cases). The infection was
      monomicrobial in 7 patients (50%) and 9 cases were community-acquired (64.2%).
      The clinical outcome of the patients was uniformly good after antibiotic
      treatment, except in 4 patients who suffered recurrence of the infection.
      CONCLUSION: A. xylosoxidans should be considered a potential pathogen in patients
      with SSTIs, especially in patients with vascular diseases or after surgery or
      trauma. A history of contact with water should be investigated in all cases.
      Treatment can be difficult due to the high level of antibiotic resistance.
      Trimethoprim-sulfamethoxazole may be useful for treatment in outpatients with
      community-acquired infections.

PMID- 24325337
TI  - Characterization of two-dimensional chiral self-assemblies L- and D-methionine on
      Au(111).
AB  - A combination of XPS, in situ RAIRS, LEED, and STM experiments together with ab
      initio DFT calculations were used to elucidate the self-assembly properties at
      the atomic level, and enabled the interpretation of the expression of surface
      chirality upon adsorption of both enantiomers of methionine on a clean Au(111)
      surface under UHV conditions. The combination of experimental results, in
      particular, LEED and STM data with quantum chemical calculations is shown to be a
      successful setup strategy for addressing this challenge. It was found that the
      methionine molecular self-assembly consists of the first molecule lying parallel
      to the gold surface and the second interacting with the first methionine through
      a 2D H-bond network. The interaction with the gold surface is weak. The stability
      of the assembly is mainly due to the presence of intermolecular H bonds,
      resulting in the formation of ziplike dimer rows on the Au(111) surface. The
      methionine molecules interact with each other via their amino acid functional
      groups. The assembly shows an asymmetric pattern due to a slightly different
      orientation of the methionine molecules with respect to the surface. Simulations
      of the STM image of methionine assemblies were consistent with the experimental
      STM image. The present study shows another example of Au(111) stabilizing a self
      assembled biological layer, which is not chemically perturbed by the surface. 

PMID- 24325338
TI  - Constructed uninterrupted charge-transfer pathways in three-dimensional
      micro/nanointerconnected carbon-based electrodes for high energy-density
      ultralight flexible supercapacitors.
AB  - A type of freestanding three-dimensional (3D) micro/nanointerconnected structure,
      with a conjunction of microsized 3D graphene networks, nanosized 3D carbon
      nanofiber (CNF) forests, and consequently loaded MnO2 nanosheets, has been
      designed as the electrodes of an ultralight flexible supercapacitor. The
      resulting 3D graphene/CNFs/MnO2 composite networks exhibit remarkable flexibility
      and highly mechanical properties due to good and intimate contacts among them,
      without current collectors and binders. Simultaneously, this designed 3D
      micro/nanointerconnected structure can provide an uninterrupted double charges
      freeway network for both electron and electrolyte ion to minimize electron
      accumulation and ion-diffusing resistance, leading to an excellent
      electrochemical performance. The ultrahigh specific capacitance of 946 F/g from
      cyclic voltammetry (CV) (or 920 F/g from galvanostatic charging/discharging
      (GCD)) were obtained, which is superior to that of the present electrode
      materials based on 3D graphene/MnO2 hybrid structure (482 F/g). Furthermore, we
      have also investigated the superior electrochemical performances of an asymmetric
      supercapacitor device (weight of less than 12 mg/cm(2) and thickness of ~0.8 mm),
      showing a total capacitance of 0.33 F/cm(2) at a window voltage of 1.8 V and a
      maximum energy density of 53.4 W h/kg for driving a digital clock for 42 min.
      These inspiring performances would make our designed supercapacitors become one
      of the most promising candidates for the future flexible and lightweight energy
      storage systems.

PMID- 24325339
TI  - Enhanced MALDI MS sensitivity by weak base additives and glycerol sample coating.
AB  - The concept of rationally designing MALDI matrices has been extended to the next
      "whole sample" level. These studies have revealed some unexpected and exploitable
      insights in improving MALDI sensitivity. It is shown that (i) additives which
      only provide additional laser energy absorption are best to be avoided; (ii) the
      addition of proton donors in the form of protonated weak bases can be highly
      beneficial; (iii) the addition of glycerol for coating crystalline samples is
      highly recommended. Overall, analytical sensitivity has been significantly
      increased compared to the current "gold" standards in MALDI MS, and new insights
      into the mechanisms and processes of MALDI have been gained. 

PMID- 24325340
TI  - Presence of spur cells as a highly predictive factor of mortality in patients
      with cirrhosis.
AB  - BACKGROUND AND AIM: The presence of spur-cell anemia (SCA) is due to lipid
      disturbances of the erythrocyte membrane and may develop in patients with
      advanced liver cirrhosis. The accurate predicting value of SC for survival has
      not been clarified. The aim of this study was to evaluate SCA as a prognostic
      indicator in patients with cirrhosis. METHODS: We prospectively evaluated
      clinical, laboratory parameters, and survival in patients with cirrhosis, with or
      without SCA, during the period 2008-2011. Patients who had at admission renal
      failure, other causes of hemolytic anemia, hepatocellular carcinoma, sepsis,
      and/or active bleeding, were excluded. One hundred sixteen patients with
      cirrhosis were included. The presence of SCA (SC rate higher or equal to 5% [>=
      5%]) was diagnosed in 36 (31%) patients. RESULTS: Patients with SCA compared to
      those without had more advanced liver disease (higher Model for End-Stage Liver
      Disease [MELD], P < 0.001), higher total bilirubin (P < 0.001), and International
      Normalized Ratio (P < 0.001). Patients with SCA had worse survival (log rank P <
      0.001). Survival of patients with SCA at the first, second, and third month of
      follow-up was 77%, 45%, and 33%, respectively. In multivariate Cox's regression
      analysis, the presence of SCA was an independent predictor of mortality (hazard
      ratio = 3.17 [95% CI 1.55-6.48]). CONCLUSIONS: The presence of spur-cell anemia
      is not uncommon in cirrhosis and seems to be strongly associated with mortality.
      SCA can be used in combination with MELD as an additional predictor of early
      mortality.

PMID- 24325341
TI  - Characterization of mesenchymal progenitor cell populations directly derived from
      human dermis.
AB  - Mesenchymal stem cell (MSC) and progenitor cell (MPC) populations in human dermis
      remain poorly characterized, despite their importance to wound repair and the
      pathogenesis of many skin diseases. To identify MSC/MPC populations in human
      dermis we developed an 11-marker flow cytometry technique that enabled sorting of
      mesenchymal cell populations for functional assays, using adipose-derived stem
      cells (ASCs) from human adipose tissue as a positive control. Two populations of
      dermal cells had similar phenotypes to ASCs: both were CD34(+) CD73(+) CD105(
      )/low, and lacked expression of c-kit (CD117) and hematopoietic or vascular
      markers (CD31, CD45, CD146, and HLA-DR). However, whereas ASCs were CD36(+/-)
      CD90(+), dermal mesenchymal progenitor cells (DMPCs) were split between a
      dominant CD36(-) CD90(+) population (DMPC1) and a small CD36(+) CD90(-)
      population (DMPC2). Both these populations were capable of differentiating into
      adipocytes, but only DMPC1 localized to a perivascular location, similar to that
      reported for ASCs. Re-gating of the flow cytometry data revealed that both DMPC1
      and DMPC2 were part of CD45(-) CD73(+) CD146(-) populations with variable
      expression of CD34. This suggests that CD34 may not be a stable marker of DMPC
      populations in human dermis, consistent with data from MSCs in human bone marrow,
      and with the loss of CD34 we observed from both ASCs and DMPCs on cell culture.
      These data enable future study of DMPCs in health and disease, and may also
      explain why some mesenchymal cell lines derived from human dermis exhibit
      characteristics of MSCs. 

PMID- 24325342
TI  - Comparing self-identified and census-defined neighborhoods among adolescents
      using GPS and accelerometer.
AB  - BACKGROUND: Numerous definitions of neighborhood exist, yet few studies have
      considered youth's perceptions of neighborhood boundaries. This study compared
      youth-identified neighborhood (YIN) boundaries to census-defined neighborhood
      (CDN) boundaries, and determined how the amount of time spent and moderate-to
      vigorous physical activity (MVPA) levels compared within both boundary types.
      METHODS: Adolescents aged 11-14 years were asked to identify their neighborhood
      boundaries using a map. Objective location and physical activity data collected
      using Global Positioning System (GPS) devices and accelerometers were used to
      calculate the amount of time spent and MVPA within youth-identified and census
      defined neighborhood boundaries. Paired bivariate analyses compared mean area
      (meters squared), percent of total time, daily MVPA (minutes), time density
      (minutes/m2) and MVPA density (minutes/m2) for both boundary types. RESULTS:
      Youth-identified neighborhoods (1,821,705 m2) and census-defined neighborhoods
      (1,277,181 m2) were not significantly different in area, p = 0.30. However,
      subjects spent more time in youth-identified neighborhoods (80.3%) than census
      defined neighborhoods (58.4%), p < 0.0001, and engaged in more daily MVPA within
      youth-identified neighborhoods (14.7 minutes) than census-defined neighborhoods
      (9.5 minutes), p < 0.0001. After adjusting for boundary area, MVPA density
      (minutes of MVPA per squared meter of area) remained significantly greater for
      youth-identified neighborhoods (2.4 * 10-4 minutes/m2) than census-defined
      neighborhoods (1.4 * 10-4 minutes/m2), p = 0.02. CONCLUSIONS: Adolescents
      perceive their neighborhoods to be similar in size to census-defined
      neighborhoods. However, youth-identified neighborhoods better capture the
      locations in which adolescents spend time and engage in physical activity. Asking
      adolescents to identify their neighborhood boundaries is a feasible and valuable
      method for identifying the spaces that adolescents are exposed to and use to be
      physically active.

PMID- 24325343
TI  - European Training and Research in Peritoneal Dialysis: scientific objectives,
      training, implementation and impact of the programme.
AB  - BACKGROUND: Peritoneal dialysis (PD) offers many advantages over hospital-based
      haemodialysis, including better quality of life. Despite this, there is a general
      under-utilisation of PD in Europe, which, to some extent, can be attributed to a
      lack of knowledge and education amongst renal clinicians and nurses. OBJECTIVES:
      The specific aim of the European Training and Research in Peritoneal Dialysis
      (EuTRiPD) programme is to address this lack of knowledge, to develop a minimum of
      five biomarkers that allow the prediction of outcome in PD and three therapeutic
      treatments to improve outcome in PD. APPROACH: EuTRiPD is a EU-wide consortium
      with clinical, academic and commercial partners set up to address this knowledge
      gap. By training through research and close collaboration between academic and
      commercial entities we hope to improve the outcome and uptake of PD. It is the
      goal of EuTRiPD to improve the currently hampered diagnostic therapeutic
      developments in renal replacement therapy (RRT) and structure existing high
      quality PD-related research across Europe. CONCLUSION: It is hoped that EuTRiPD
      can and will have a significant impact on socio-economic and scientific aspects
      of PD. It is the aim for EuTRiPD to boost the uptake of PD throughout Europe by
      making PD the obvious choice for patients.

PMID- 24325344
TI  - Microsatellite-based genetic diversity among accessions of maize landraces from
      Sinaloa in Mexico.
AB  - In the state of Sinaloa Mexico, traditional farmers still cultivate maize
      accessions with a wide diversity of morphological characteristics, but the gene
      reservoir maintained in these populations has been poorly studied and it is being
      lost due to changes in land use and the adoption of hybrid commercial varieties.
      The aim of this study was to evaluate the genetic diversity of some of these
      maize populations to contribute to their preservation. Twenty eight accessions
      were used for the analysis. DNA was extracted from 396 individuals and probed
      with 20 microsatellites distributed across the maize genome. A total of 121
      alleles were obtained (average of 6.1 alleles per locus) and a total genetic
      diversity of 0.72. The UPGMA-cluster analysis, model-based population structure
      and principal component analysis revealed three major groups, one formed mainly
      by accessions of races typical of the Northwestern lowlands (Chapalote, Dulcillo
      del Noroeste, Tabloncillo Perla, Blando de Sonora and Elotero de Sinaloa) and the
      other two with accessions mainly from Tabloncillo and Tuxpeno. The high number of
      alleles per locus and total genetic diversity found in this study demonstrate a
      broad genetic basis of the accessions of maize landraces from Sinaloa,
      representing a gene reservoir useful in breeding programs. 

PMID- 24325346
TI  - Cellular and molecular mechanisms in cancer immune escape: a comprehensive
      review.
AB  - Immune escape is the final phase of cancer immunoediting process wherein cancer
      modulates our immune system to escape from being destroyed by it. Many cellular
      and molecular events govern the cancer's evasion of host immune response. The
      tumor undergoes continuous remodeling at the genetic, epigenetic and metabolic
      level to acquire resistance to apoptosis. At the same time, it effectively
      modifies all the components of the host's immunome so as to escape from its
      antitumor effects. Moreover, it induces accumulation of suppressive cells like
      Treg and myeloid derived suppressor cells and factors which also enable it to
      elude the immune system. Recent research in this area helps in defining the role
      of newer players like miRNAs and exosomes in immune escape. The immunotherapeutic
      approaches developed to target the escape phase appear quite promising; however,
      the quest for a perfect therapeutic agent that can achieve maximum cure with
      minimal toxicity continues. 

PMID- 24325347
TI  - Maternal ABO and rhesus blood group phenotypes and hepatitis B surface antigen
      carriage.
AB  - In view of a persistently high prevalence of hepatitis B surface antigen (HBsAg)
      carriage in our obstetric population, we examined the association between HBsAg
      carriage with maternal ABO and rhesus (Rh) blood group phenotypes determined at
      routine antenatal screening. In a retrospective study, the antenatal screening
      results of women booked for confinement between 1998 and 2011 in our hospital
      were examined for the relationship between HBsAg carriage with the ABO and rhesus
      blood groups, taking into account also the effects of advanced maternal age (>=
      35 years) and parity status (nulliparous or multiparous), and year of birth
      before or following the availability of the hepatitis B vaccine (1984). HBsAg
      carriage was found in 9.9%, 9.6%, 9.1% and 10.2% (P = 0.037) for group-A (n = 20
      581 or 26.1%), -B (n = 20 744 or 26.4%), -AB (n = 5138 or 6.5%) and -O (n = 32
      242 or 41.0%) among the 78705 women in the study cohort. Rhesus negativity was
      found in 0.6%, and HBsAg carriage was 12.3% and 9.8%, respectively, for the Rh
      negative and Rh-positive women (P = 0.071). Carriage rate between group-O and non
      O was influenced by nulliparity, age >= 35 years and Rh-positive status.
      Regression analysis indicated that group-B (P = 0.044, aOR = 1.062, 95% CI 1.002
      1.127) and group-AB (P = 0.016, aOR = 1.134, 95% CI 1.024-1.256) were associated
      with HBsAg carriage. Blood groups-B and -AB are associated with increased
      hepatitis B virus (HBV) infection in our population, and further studies are
      warranted to elucidate the implications of this on the sequelae of HBV infection.

PMID- 24325345
TI  - Aging is associated with increased regulatory T-cell function.
AB  - Regulatory T-cell (Treg, CD4(+) CD25(+)) dysfunction is suspected to play a key
      role in immune senescence and contributes to increased susceptibility to diseases
      with age by suppressing T-cell responses. FoxP3 is a master regulator of Treg
      function, and its expression is under control of several epigenetically labile
      promoters and enhancers. Demethylation of CpG sites within these regions is
      associated with increased FoxP3 expression and development of a suppressive
      phenotype. We examined differences in FoxP3 expression between young (3-4 months)
      and aged (18-20 months) C57BL/6 mice. DNA from CD4(+) T cells is hypomethylated
      in aged mice, which also exhibit increased Treg numbers and FoxP3 expression.
      Additionally, Treg from aged mice also have greater ability to suppress effector
      T-cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged
      mice exhibit greater redox remodeling-mediated suppression of Teff proliferation
      during coculture with DCs by decreasing extracellular cysteine availability to a
      greater extent than Tregs from young mice, creating an adverse environment for
      Teff proliferation. Tregs from aged mice produce higher IL-10 levels and suppress
      CD86 expression on DCs more strongly than Tregs from young mice, suggesting
      decreased T-cell activity. Taken together, these results reveal a potential
      mechanism of higher Treg-mediated activity that may contribute to increased
      immune suppression with age.

PMID- 24325349
TI  - Are children's psychological self-concepts predictive of their self reported
      activity preferences and leisure participation?
AB  - BACKGROUND/AIM: Participation in leisure and play activities is recognised as an
      important outcome in occupational therapy for children. To investigate whether
      children's psychological self-concept are predictive of their activity
      preferences and leisure participation. METHOD: A group of 38 healthy children
      aged 10-14 years from Victoria, Australia completed the Piers-Harris Self Concept
      Scale (Piers Harris-2) and the Children's Assessment of Participation and
      Enjoyment/Preferences for Activities of Children (CAPE/PAC). Correlation and
      regression analyses were completed to investigate the predictive relationships
      between the Pier Harris-2 and the CAPE/PAC. RESULTS: The Piers Harris-2
      Intellectual and School Status subscale was found to be predictive of children's
      Overall Enjoyment of Participation as measured on the CAPE, explaining 21.9% of
      the total variance (beta = 0.566, P < 0.01). The Piers Harris-2 Freedom from
      Anxiety subscale made a unique contribution to children's preferences for skill
      based activities as measured by the PAC, explaining 18.9% of the total variance
      (beta = -.435, P < 0.01). Children's gender accounted for 22.7% of the total
      variance of the PAC Physical Activities subscale (beta = -.476, P <= 0.01) and
      14.6% of the PAC Preferences for Skill-Based Activities subscale (beta = 0.382, P
      <= 0.05) while age made unique contributions to the PAC Social Activities
      subscale (beta = -0.418, P <= 0.01) explaining 17.5% of its total variance.
      CONCLUSION: This study provides evidence that children's psychological self
      concept, age and gender are predictive of components of children's activity
      preferences and leisure participation. In particular, participation enjoyment is
      influenced by their perceived self-esteem and how well they do at school. Further
      investigation of this topic is recommended.

PMID- 24325348
TI  - Regulation of cyp26a1 on Th17 cells in mouse peri-implantation.
AB  - Cytochrome P450 26A1 (cyp26a1) is expressed in the mouse uterus during peri
      implantation. The repression of this protein is closely associated with a
      reduction in implantation sites, suggesting a specific role for cyp26a1 in
      pregnancy and prompting questions concerning how a metabolic enzyme can generate
      this distinct outcome. To explore the effective downstream targets of cyp26a1 and
      confirm if its role in peri-implantation depends on its metabolic substrate RA
      (retinoic acid), we characterized the changes in the peripheral blood, spleen and
      uterine implantation sites using the cyp26a1 gene vaccine constructed before.
      Flow cytometry results showed a significant increase in CD4(+) RORgammat(+) Th17
      cells in both the peripheral blood and spleen in the experimental group. The
      expression of RORgammat and IL-17 presented the Th17 cells reduction in uterus
      followed by the suppression of cyp26a1 expression. For greater certainty, cyp26a1
      antibody blocking model and RNA interference model were constructed to determine
      the precise target immune cell group. High performance liquid chromatography
      results showed a significant increase in uterine at-RA followed by the
      immunization of cyp26a1 gene vaccine. Both the ascertain by measuring RARalpha
      protein levels in peri-implantation uterus after gene vaccine immunization and
      researches using the specific agonist and antagonist against RARalpha suggested
      that RARalpha may be the main RA receptor for signal transduction. These results
      provided more evidence for the signal messenger role of RA in cyp26a1 regulation
      from the other side. Here, we showed that the cyp26a1-regulated Th17 cells are
      dependent on at-RA signalling, which is delivered through RARalpha in mouse peri
      implantation. 

PMID- 24325350
TI  - Association study between SNP rs150689919 in the DNA demethylation gene, TET1,
      and Parkinson's disease in Chinese Han population.
AB  - BACKGROUND: Recent studies suggest that epigenetic factors may play an important
      role in the pathogenesis of Parkinson's disease (PD). In our previous work, we
      sequenced the exomes of sixteen patients from eight Chinese PD families using
      whole exome sequencing technology, consequently three patients from different
      pedigrees were found sharing the variant c.1460C > T (rs150689919) in the coding
      region of the Tet methyl cytosine dioxygenase 1 (TET1) gene. METHODS: In order to
      evaluate the possible association between sporadic PD and the single nucleotide
      polymorphism (SNP) rs150689919 in TET1, a case-control cohort study was conducted
      in 514 sporadic PD patients and 529 normal controls. Genotyping was determined by
      PCR and direct sequencing. Statistical significance was analyzed by the Chi
      squared test. RESULTS: There was no statistical significance in TET1 rs150689919
      genotype or allele frequencies between the PD cases and healthy controls, even
      after being stratified by gender and age at onset. CONCLUSIONS: Our findings
      suggest that rs150689919 in TET1 may not be associated with PD in Chinese
      population. However, due to the limited data in this study, replication studies
      in larger sample and other populations are required.

PMID- 24325351
TI  - Leukocytes and systemic inflammatory response syndrome as prognostic factors in
      pulmonary embolism patients.
AB  - BACKGROUND: Hemodynamic status and cardiac function are important factors for
      predicting pulmonary embolism (PE) prognosis. Although inflammation is considered
      a risk factor for deep vein thrombosis, the prognostic significance of both
      systemic inflammatory response syndrome (SIRS) and leukocytosis has not been
      elucidated. This study evaluates PE prognostic factors, including SIRS and
      leukocytes. METHODS: This retrospective cohort study included 667 PE patients.
      Risk evaluation included SIRS and leukocytosis. A prediction model was developed
      based on independent predictors of 30-day mortality. RESULTS: Fifty-seven
      patients (8.5%) died within 30 days of PE. Multivariate analysis showed that SIRS
      satisfying the WBC criteria (odds ratio [OR], 2.8; 95% confidence interval [CI],
      1.5-5.4), altered mental status (OR, 4.0; 95% CI, 1.8-8.7), shock (OR, 2.6; 95%
      CI, 1.0-7.1), and right-to-left ventricle diameter ratio (OR, 1.7; 95% CI, 1.0
      2.8) were associated with 30-day mortality. SIRS criteria, including body
      temperature (OR, 4.6; 95% CI, 1.4-14.8), heart rate (OR, 2.0; 95% CI, 1.1-3.6),
      respiratory rate (OR, 2.5; 95% CI, 1.4-4.6), and white blood cells (WBC) count
      (OR, 1.9; 95% CI, 1.2-3.5) predicted short-term mortality following PE. The area
      under the receiver operating characteristic curve for the prognostic model
      performance was 0.76 (95% CI, 0.66-0.85); pulmonary embolism severity index
      (PESI) and PESI + WBC count were 0.72 (95% CI, 0.68-0.75) and 0.76 (95% CI, 0.72
      0.79, P < 0.001 versus PESI), respectively. CONCLUSIONS: Leukocytosis and SIRS
      are important factors in determining short-term outcomes in PE patients.

PMID- 24325352
TI  - Pachymetry map of corneal epithelium in children wearing orthokeratology contact
      lenses.
AB  - PURPOSE: To study the pachymetry map of the corneal epithelium in children
      wearing orthokeratology lenses automatically generated by a Fourier-domain
      optical coherence tomography. MATERIALS AND METHOD: The study was conducted on 60
      children who had been fitted with myopic orthokeratology lenses. Patients were
      divided into two groups according to the duration of OK lens treatment (group 1:
      <=14 days, n = 28; group 2: >14 days, n = 32). The control group consisted of 44
      children. An FD-OCT device with a pachymetry module was used to map the central 6
      mm corneal epithelial thickness. An epithelial thickness map was automatically
      generated and divided into three zones: central 2 mm, paracentral 2 to 5 mm (P1)
      and mid-peripheral 5 to 6 mm (P2). The average epithelial thickness of central
      (C), the temporal (T1), nasal (N1), superior (S1) and inferior (I1) sectors of
      P1, and the temporal (T2), nasal (N2), superior (S2) and inferior (I2) sectors of
      P2 were recorded and compared. The minimum and maximum points of epithelial
      thickness across the map were also recorded. Munnerlyn's formula was used to
      model the expected change in refractive error based on Delta(Max-Min) (Delta(Max
      Min) = (Max-Min)study-(Max-Min) mean of control). RESULTS: The central epithelial
      thickness was significantly different between individual groups and a significant
      difference from the control (Group 0) was seen in each treatment group. Both the
      epithelial thickness measurements of T1 and I1 were thinnest in Group 1. Both the
      epithelial thickness measurements of S2 and I2 were thickest in Group 2. The
      difference between maximum and minimum thickness was significantly different
      between groups with the largest effect in Group 2. The refractive changes
      predicted by Munnerlyn's formula were less than the actual refractive changes
      measured in both study groups. CONCLUSIONS: The epithelial thickness map
      automatically generated by FD-OCT can provide regional information about corneal
      epithelium thickness following overnight wearing of OK lenses.

PMID- 24325353
TI  - A low Dicer expression is associated with resistance to 5-FU-based
      chemoradiotherapy and a shorter overall survival in patients with oral squamous
      cell carcinoma.
AB  - BACKGROUND: The deregulation of microRNA (miRNA) is associated with multiple
      processes involved in cancer progression. RNase III endonucleases, Dicer and
      Drosha, are key enzymes for miRNA biogenesis, and it has been reported that
      altered expressions of these molecules affect the clinical outcomes of patients
      with various cancers. However, the clinical value of measuring the levels of
      Dicer and Drosha in oral squamous cell carcinoma (OSCC) patients is unclear. The
      purpose of this study was to determine the clinical significance of the
      expressions of Dicer and Drosha in patients with OSCC. METHODS: Oral squamous
      cell carcinoma specimens were obtained from 61 patients who underwent surgery
      following 5-fluorouracil-based chemoradiotherapy at Kumamoto University Hospital
      between October 2003 and January 2009. Paraffin-embedded sections obtained from
      biopsy specimens were immunohistochemically analyzed. The associations between
      Dicer, Drosha, and various clinicopathological features were examined, and the
      effects of Dicer and Drosha on the prognosis were evaluated. RESULTS: A low Dicer
      tumor expression was significantly correlated with the pathological response to
      chemoradiotherapy. Furthermore, a Cox regression analysis based on the overall
      survival revealed the Dicer expression status (hazard ratio, 0.34; P = 0.048) and
      pathological response to chemoradiotherapy (hazard ratio, 0.21; P = 0.014) to be
      significant prognostic factors in OSCC patients. On the other hand, the Drosha
      expression was not associated with any clinicopathological features or the
      prognosis. CONCLUSION: These results suggest that Dicer is a potential biomarker
      for predicting the clinical response to 5-FU-based chemoradiotherapy and the
      overall survival in patients with OSCC.

PMID- 24325354
TI  - Umbelliprenin induced production of IFN-gamma and TNF-alpha, and reduced IL-10,
      IL-4, Foxp3 and TGF-beta in a mouse model of lung cancer.
AB  - Umbelliprenin is a member of the 7-prenyloxycoumarins with potential therapeutic
      properties such as cytotoxic effects on various cancer cells. The present study
      investigates the effect of umbelliprenin on predominance of Th1 and Th2 responses
      in Lewis lung cancer (LLC) mouse model. The cytotoxic effect of umbelliprenin was
      explored on LLC cells and mouse splenocytes by MTT assay. Mice into which LLC had
      been transplanted were treated with umbelliprenin on alternate days, at 2.5
      mg/200 ul intraperitoneally. Foxp3, TNF-alpha and TGF-beta mRNA expressions were
      assessed in tumor and lung tissues of LLC mice. In addition, IL-10, IFN-gamma and
      IL-4 levels were determined in sera and also in splenocyte culture supernatants
      at the presence of tumor cell lysate (10 ug/ml) and Con A (3 ug/ml) after 72 h.
      Results showed the cytotoxic effects of umbelliprenin on LLC cells (IC50 = 51.6
      +/- 5.4 uM) while no adverse effect was seen at this concentration on normal
      splenocytes. TNF-alpha mRNA expression in both lung and tumor tissues was
      increased. However, Foxp3 and TGF-beta expressions were decreased in tumor
      tissues. Serum level of IFN-gamma was elevated in the umbelliprenin treated
      cancerous mice compared to the control group while IL-10 and IL-4 secretions were
      reduced. Tumor size was also decreased in umbelliprenin treated group. In
      summary, umbelliprenin has shown a partially Th1 bias with a reduction of
      regulatory immune response. Although the mechanism behind this action is not
      known, it is speculated that upon changing the Th1/Th2 balance in favour of Th1,
      umbelliprenin induces its antitumor activity.

PMID- 24325355
TI  - Optimal design of porous structures for the fastest liquid absorption.
AB  - Porous materials engineered for rapid liquid absorption are useful in many
      applications, including oil recovery, spacecraft life-support systems, moisture
      management fabrics, medical wound dressings, and microfluidic devices. Dynamic
      absorption in capillary tubes and porous media is driven by the capillary
      pressure, which is inversely proportional to the pore size. On the other hand,
      the permeability of porous materials scales with the square of the pore size. The
      dynamic competition between these two superimposed mechanisms for liquid
      absorption through a heterogeneous porous structure may lead to an overall
      minimum absorption time. In this work, we explore liquid absorption in two
      different heterogeneous porous structures [three-dimensional (3D) circular tubes
      and porous layers], which are composed of two sections with variations in
      radius/porosity and height. The absorption time to fill the voids of porous
      constructs is expressed as a function of radius/porosity and height of local
      sections, and the absorption process does not follow the classic Washburn's law.
      Under given height and void volume, these two-section structures with a negative
      gradient of radius/porosity against the absorption direction are shown to have
      faster absorption rates than control samples with uniform radius/porosity. In
      particular, optimal structural parameters, including radius/porosity and height,
      are found that account for the minimum absorption time. The liquid absorption in
      the optimized porous structure is up to 38% faster than in a control sample. The
      results obtained can be used a priori for the design of porous structures with
      excellent liquid management property in various fields. 

PMID- 24325356
TI  - Somatic mutations of calreticulin in myeloproliferative neoplasms.
AB  - BACKGROUND: Approximately 50 to 60% of patients with essential thrombocythemia or
      primary myelofibrosis carry a mutation in the Janus kinase 2 gene (JAK2), and an
      additional 5 to 10% have activating mutations in the thrombopoietin receptor gene
      (MPL). So far, no specific molecular marker has been identified in the remaining
      30 to 45% of patients. METHODS: We performed whole-exome sequencing to identify
      somatically acquired mutations in six patients who had primary myelofibrosis
      without mutations in JAK2 or MPL. Resequencing of CALR, encoding calreticulin,
      was then performed in cohorts of patients with myeloid neoplasms. RESULTS:
      Somatic insertions or deletions in exon 9 of CALR were detected in all patients
      who underwent whole-exome sequencing. Resequencing in 1107 samples from patients
      with myeloproliferative neoplasms showed that CALR mutations were absent in
      polycythemia vera. In essential thrombocythemia and primary myelofibrosis, CALR
      mutations and JAK2 and MPL mutations were mutually exclusive. Among patients with
      essential thrombocythemia or primary myelofibrosis with nonmutated JAK2 or MPL,
      CALR mutations were detected in 67% of those with essential thrombocythemia and
      88% of those with primary myelofibrosis. A total of 36 types of insertions or
      deletions were identified that all cause a frameshift to the same alternative
      reading frame and generate a novel C-terminal peptide in the mutant calreticulin.
      Overexpression of the most frequent CALR deletion caused cytokine-independent
      growth in vitro owing to the activation of signal transducer and activator of
      transcription 5 (STAT5) by means of an unknown mechanism. Patients with mutated
      CALR had a lower risk of thrombosis and longer overall survival than patients
      with mutated JAK2. CONCLUSIONS: Most patients with essential thrombocythemia or
      primary myelofibrosis that was not associated with a JAK2 or MPL alteration
      carried a somatic mutation in CALR. The clinical course in these patients was
      more indolent than that in patients with the JAK2 V617F mutation. (Funded by the
      MPN Research Foundation and Associazione Italiana per la Ricerca sul Cancro.).

PMID- 24325357
TI  - Another piece of the myeloproliferative neoplasms puzzle.

PMID- 24325358
TI  - A dominant-negative GFI1B mutation in the gray platelet syndrome.
AB  - The gray platelet syndrome is a hereditary, usually autosomal recessive bleeding
      disorder caused by a deficiency of alpha granules in platelets. We detected a
      nonsense mutation in the gene encoding the transcription factor GFI1B (growth
      factor independent 1B) that causes autosomal dominant gray platelet syndrome.
      Both gray platelets and megakaryocytes had abnormal marker expression. In
      addition, the megakaryocytes had dysplastic features, and they were abnormally
      distributed in the bone marrow. The GFI1B mutant protein inhibited nonmutant
      GFI1B transcriptional activity in a dominant-negative manner. Our studies show
      that GFI1B, in addition to being causally related to the gray platelet syndrome,
      is key to megakaryocyte and platelet development. 

PMID- 24325360
TI  - Real-time monitoring of in situ gas-phase H/D exchange reactions of cations by
      atmospheric pressure helium plasma ionization mass spectrometry (HePI-MS).
AB  - An enclosed atmospheric-pressure helium-plasma ionization (HePI-MS) source
      avoids, or minimizes, undesired back-exchange reactions usually encountered
      during deuterium incorporation experiments under ambient-pressure open-source
      conditions. A simple adaptation of an ESI source provides an economical way of
      conducting gas phase hydrogen/deuterium (H/D) exchange reactions (HDX) in real
      time without the need for complicated hardware modifications. For example, the
      spectrum of [(2)H8]toluene recorded under exposed ambient conditions showed the
      base peak at m/z 96 due to fast leaching of ring hydrogens because of
      interactions with H2O vapor present in the open source. Such D/H exchanges are
      rapidly reversed if the deuterium-depleted [(2)H8]toluene is exposed to D2O
      vapor. In addition to the enumeration of labile protons, our procedure enables
      the identification of protonation sites in molecules unambiguously, by the number
      of H/D exchanges observed in real time. For example, molecules such as
      tetrahydrofuran and pyridine protonate at the heteroatom and consequently undergo
      only one H/D exchange, whereas ethylbenzene, which protonates at a ring position
      of the aromatic ring, undergoes six H/D exchanges. In addition, carbocations
      generated in situ by in-source fragmentation of precursor protonated species,
      such as benzyl alcohol, do not undergo any rapid H/D exchanges. Because radical
      cations, second-generation cations (ions formed by losing a small molecule from a
      precursor ion), or those formed by hydride abstraction do not undergo rapid H/D
      exchanges, our technique provides a way to distinguish these ions from protonated
      molecules. 

PMID- 24325361
TI  - Probing the redox states at the surface of electroactive nanoporous NiO thin
      films.
AB  - Nanoporous NiO thin film electrodes were obtained via plasma-assisted microwave
      sintering and characterized by means of a combination of electrochemical
      techniques and X-ray photoelectron spectroscopy (XPS). The aim of this study is
      the elucidation of the nature of the surface changes introduced by the redox
      processes of this nanostructured material. NiO undergoes two distinct
      electrochemical processes of oxidation in aqueous electrolyte with the progress
      of NiO anodic polarization. These findings are consistent with the sequential
      formation of oxyhydroxide species at the surface, the chemical nature of which
      was assessed by XPS. Electronic relaxation effects in the Ni 2p spectra clearly
      indicated that the superficial oxyhydroxide species resulted to be beta-NiOOH and
      gamma-NiOOH. We also show for the first time spectral evidence of an
      electrochemically generated Ni(IV) species. This study has direct relevance for
      those applications in which NiO electrodes are utilized in aqueous electrolyte,
      namely catalytic water splitting or electrochromism, and may constitute a
      starting point for the comprehension of electronic phenomena at the NiO/organic
      electrolyte interface of cathodic dye-sensitized solar cells (p-DSCs). 

PMID- 24325359
TI  - Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.
AB  - BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many
      myeloproliferative neoplasms, but the molecular pathogenesis of
      myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis
      of these neoplasms remains a challenge. METHODS: We performed exome sequencing of
      samples obtained from 151 patients with myeloproliferative neoplasms. The
      mutation status of the gene encoding calreticulin (CALR) was assessed in an
      additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We
      established phylogenetic trees using hematopoietic colonies. We assessed
      calreticulin subcellular localization using immunofluorescence and flow
      cytometry. RESULTS: Exome sequencing identified 1498 mutations in 151 patients,
      with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of
      polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively.
      Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative
      neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional
      samples of other myeloid cancers, and in none of the other cancers. A total of
      148 CALR mutations were identified with 19 distinct variants. Mutations were
      located in exon 9 and generated a +1 base-pair frameshift, which would result in
      a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the
      endoplasmic reticulum without increased cell-surface or Golgi accumulation.
      Patients with myeloproliferative neoplasms carrying CALR mutations presented with
      higher platelet counts and lower hemoglobin levels than patients with mutated
      JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells.
      Clonal analyses showed CALR mutations in the earliest phylogenetic node, a
      finding consistent with its role as an initiating mutation in some patients.
      CONCLUSIONS: Somatic mutations in the endoplasmic reticulum chaperone CALR were
      found in a majority of patients with myeloproliferative neoplasms with nonmutated
      JAK2. (Funded by the Kay Kendall Leukaemia Fund and others.).

PMID- 24325362
TI  - Symptomatic polycystic liver disease treated with transcatheter hepatic arterial
      embolization and inferior vena cava stenting: a case report.
AB  - Autosomal-dominant polycystic kidney disease is frequently complicated by
      polycystic liver disease. Some patients with polycystic liver disease have a full
      stomach sensation and intractable ascites. We report a 56-year-old woman with
      polycystic liver disease waiting to receive a liver transplant, with a chief
      complaint of a full-stomach sensation and refractory ascites, wherein the
      transcatheter hepatic arterial embolization and inferior vena cava stenting were
      begun simultaneously, and the signs were favorably alleviated. It is important to
      recognize the risk of liver failure after the complete embolization of both the
      right and left hepatic arteries; however, performance of transcatheter hepatic
      arterial embolization and inferior vena cava stent placement also are indicated
      for patients awaiting a liver transplant for early alleviation of symptoms. 

PMID- 24325364
TI  - Considerations on the possible origins of fetal hemoglobin cells produced in
      developing tumors.
AB  - Although tumor angiogenesis in relation to cancer therapy has been widely
      investigated for more than four decades, its counterpart tumor hematopoiesis has
      not been equally considered. In that respect, in our long-term
      immunohistochemical examination of fetal hemoglobin (HbF) cells in various solid
      tumors, we have observed signs of fetal hematopoiesis in situ within the tumors.
      We hypothesize that this observed fetal hematopoiesis, involving angiogenesis,
      mirrors mammalian blood system development in the embryo and the fetus; this is
      consistent with the concept of the hemogenic endothelial progenitor, common to
      endothelial and hemopoietic cells. Based on this assumption, there should exist
      in tumors at least two routes of hematoangiogenesis: one of fetal (HbF)
      hematopoiesis and the other of adult (HbA) hematopoiesis, each one deserving a
      different therapeutic approach. In the fetal route, HbF should support tumor
      growth by virtue of its high oxygen affinity. 

PMID- 24325363
TI  - DKK1 promotes hepatocellular carcinoma cell migration and invasion through beta
      catenin/MMP7 signaling pathway.
AB  - BACKGROUND: Recently several reports have indicated that elevated expression of
      DKK1 is tightly associated with the progression of hepatocellular carcinoma
      (HCC). However, the biological function of DKK1 in HCC has not yet been well
      documented. METHODS: In this study, the role of DKK1 in tumor cell proliferation,
      migration and invasion was investigated using MTT, colony formation, wound
      scratch, transwell assays, and also human HCC samples. RESULTS: Both gain- and
      loss-of-function studies showed that DKK1 did not influence the tumor cell
      proliferation and colony formation, while dramatically promoted HCC cell
      migration and invasion. Subsequent investigations revealed that beta-catenin was
      an important target of DKK1. The blocking of beta-catenin by pharmacological
      inhibitor antagonized the function of DKK1, whereas introduction of beta-catenin
      by transfection with plasmids or treatment with GSK3beta inhibitor phenocopied
      the pro-migration and pro-invasion effects of DKK1. We further disclosed that
      DKK1 exerted its pro-invasion function, at least in part, by promoting beta
      catenin expression, in turn, upregulating the expression of matrix
      metalloproteinase 7 (MMP7), which was independent of the canonical Wnt signaling
      pathway. Moreover, introduction of MMP7 significantly enhanced the ability of HCC
      cells to invade extracellular matrix gel in vitro. Consistently, in human HCC
      tissues, DKK1 level was positively correlated with beta-catenin expression, as
      well as tumor metastasis. CONCLUSION: Taken together, these results demonstrated
      that DKK1 is overexpressed in HCC; moreover, ectopic expression DKK1 promotes HCC
      cell migration and invasion at least partly through beta-catenin/MMP7 signaling
      axis, suggesting that DKK1 may be a promising target for HCC therapy.

PMID- 24325365
TI  - Pharmacokinetics of a new once-daily controlled-release sarpogrelate
      hydrochloride compared with immediate-release formulation and the effect of food.
AB  - WHAT IS KNOWN AND OBJECTIVE: Sarpogrelate is a selective 5-hydroxytryptamine
      receptor subtype 2A antagonist that inhibits platelet aggregation and
      vasoconstriction. The aim of this study was to compare the pharmacokinetics of a
      sarpogrelate controlled-release formulation (CR) with those of the immediate
      release formulation (IR). The effect of food on the pharmacokinetics of CR
      sarpogrelate was also evaluated. METHODS: A randomized, open-label, 3-period, 3
      treatment crossover study was conducted in 50 healthy male subjects. Subjects
      were allocated into one of six sequence groups. In one period, a 100-mg IR
      formulation was administered three times at 6-h intervals, and in the other two
      periods, a 300-mg CR formulation was administered once to fasting and once to fed
      subjects. Each period was separated by a 7-day washout period. Serial blood
      samples were collected up to 24 h after the first drug administration in each
      period. The plasma concentrations of sarpogrelate were analysed by liquid
      chromatography-tandem mass spectrometry. Pharmacokinetic parameters were
      calculated by non-compartmental methods. RESULTS AND DISCUSSION: After the
      administration of the IR formulation, the plasma concentration reached a peak at
      0.48 h and the drug was eliminated with a half-life (t1/2 ) of 0.7 h. After
      administration of the CR formulation, the plasma concentration reached a peak at
      0.5 h and the drug was eliminated with a t1/2 of 3.23 h. The geometric mean
      ratios (CR/IR) for sarpogrelate area under the plasma concentration-time curve
      (AUC) and the maximum plasma drug concentration (Cmax) were 1.2040 (90%
      confidence interval (CI): 1.0992-1.3188) and 0.9462 (90% CI: 0.8504-1.0529). When
      CR was administered to fed subjects, the time to peak concentration was prolonged
      to 3.97 h and t1/2 was shortened to 1.45 h. The geometric mean ratios
      (fasting/fed) for sarpogrelate AUC and Cmax were 0.8573 (90% CI: 0.7687-0.9561)
      and 0.6452 (90% CI: 0.5671-0.7341). WHAT IS NEW AND CONCLUSION: After the
      administration of CR and IR formulations of the same daily dose of sarpogrelate
      hydrochloride, the overall systemic exposure was slightly higher for the CR than
      for the IR formulation, whereas peak concentration was comparable between the two
      formulations. Food reduced the bioavailability of sarpogrelate CR.

PMID- 24325367
TI  - Editorial for issue 3 of 2013, Journal of Evidence Based Medicine.

PMID- 24325366
TI  - Glutaredoxin-1 attenuates S-glutathionylation of the death receptor fas and
      decreases resolution of Pseudomonas aeruginosa pneumonia.
AB  - RATIONALE: The death receptor Fas is critical for bacterial clearance and
      survival of mice after Pseudomonas aeruginosa infection. OBJECTIVES: Fas ligand
      (FasL)-induced apoptosis is augmented by S-glutathionylation of Fas (Fas-SSG),
      which can be reversed by glutaredoxin-1 (Grx1). Therefore, the objective of this
      study was to investigate the interplay between Grx1 and Fas in regulating the
      clearance of P. aeruginosa infection. METHODS: Lung samples from patients with
      bronchopneumonia were analyzed by immunofluorescence. Primary tracheal epithelial
      cells, mice lacking the gene for Grx1 (Glrx1(-/-)), Glrx1(-/-) mice treated with
      caspase inhibitor, or transgenic mice overexpressing Grx1 in the airway
      epithelium were analyzed after infection with P. aeruginosa. MEASUREMENTS AND
      MAIN RESULTS: Patient lung samples positive for P. aeruginosa infection
      demonstrated increased Fas-SSG compared with normal lung samples. Compared with
      wild-type primary lung epithelial cells, infection of Glrx1(-/-) cells with P.
      aeruginosa showed enhanced caspase 8 and 3 activities and cell death in
      association with increases in Fas-SSG. Infection of Glrx1(-/-) mice with P.
      aeruginosa resulted in enhanced caspase activity and increased Fas-SSG as
      compared with wild-type littermates. Absence of Glrx1 significantly enhanced
      bacterial clearance, and decreased mortality postinfection with P. aeruginosa.
      Inhibition of caspases significantly decreased bacterial clearance postinfection
      with P. aeruginosa, in association with decreased Fas-SSG. In contrast,
      transgenic mice that overexpress Grx1 in lung epithelial cells had significantly
      higher lung bacterial loads, enhanced mortality, decreased caspase activation,
      and Fas-SSG in the lung after infection with P. aeruginosa, compared with wild
      type control animals. CONCLUSIONS: These results suggest that S-glutathionylation
      of Fas within the lung epithelium enhances epithelial apoptosis and promotes
      clearance of P. aeruginosa and that glutaredoxin-1 impairs bacterial clearance
      and increases the severity of pneumonia in association with deglutathionylation
      of Fas.

PMID- 24325368
TI  - Systematic review of interventions on antibiotic prophylaxis in surgery in
      Chinese hospitals during 2000-2012.
AB  - OBJECTIVE: To systematically review intervention studies on antibiotic
      prophylaxis in clean or clean-contaminated surgery in Chinese hospitals from 2000
      to 2012. METHODS: Published peer reviewed articles, unpublished documents and
      reports, and gray literature were identified through searching CNKI, CBM, VIP,
      PubMed (MEDLINE), WHO database, and the official websites of the Ministry of
      Health of China, provincial health authorities and medical university internal
      publications. RESULTS: Eighty-two studies were identified. Circulation and
      localization of central rules, regulations and guidelines; clinical pharmacists'
      involvement; technical, administrative, and managerial strategies were the mostly
      adopted interventions. Except one study, all claimed effectiveness of
      interventions. Limited effects were observed for non-indicated clean surgery.
      Huge gaps still existed between the international agreed guidelines and the
      claimed best performance following interventions. The following were critical to
      have more effective interventions: recognition, acceptance, and enforcement
      strategies of rules, regulations, and guidelines; intervention persistence and
      intensity; health information system; removal of health system perverse
      incentives; patient-doctor relationship; public education; and access to unbiased
      medicines information. A total 4 of 82 studies were pre-post studies with
      control; all others were simple pre-post studies without control. Simple
      measurement of the outcome indicators as an average for pre-post intervention
      groups and changes in between failed to distinguish the real intervention effect
      from confounding factors, and failed to adjust underlying trends. CONCLUSIONS:
      Interventions on surgical antibiotic prophylaxis in Chinese hospitals during 2000
      2012 brought limited positive effects. There are still huge gaps between the
      Chinese situation and internationally agreed standards. More advanced study
      methodologies are needed to have better documentation of evidence of the most
      effective interventions.

PMID- 24325369
TI  - SWAT 1: what effects do site visits by the principal investigator have on
      recruitment in a multicentre randomized trial?
AB  - The SWAT (Study Within A Trial) programme has been established to develop a
      series of studies that would embed research within research, so as to resolve
      uncertainties about the effects of different ways of designing, conducting,
      analyzing and interpreting evaluations of health and social care. It was
      described in an Education piece in the Journal of Evidence-Based Medicine in
      2012. We have now prepared the first example of the design summary for a SWAT,
      using the template that will be used for other SWAT. This is presented in this
      article. 

PMID- 24325370
TI  - Investigation on the governance model and effect of medical schools merged with
      comprehensive universities in China.
AB  - This investigation analyzes the management of medical schools merged with
      comprehensive universities through internet search and research review to reveal
      management model and effect of the merger. The conclusion is safely reached that
      governance models are divided into two different patterns: centralized management
      and decentralized management. Eight universities, representing the two models,
      were selected and evaluated comprehensively. Among them, the universities that
      carried out decentralized management have greater development after the merger
      based on a quality comparison concerning freshmen, faculty, teaching, and
      research between the two patterns. 

PMID- 24325371
TI  - Epidemiology of pulmonary tuberculosis in Wenchuan earthquake stricken area:
      population-based study.
AB  - OBJECTIVES: To explore spatio-temporal distribution and associated factors of
      pulmonary tuberculosis in Wenchuan earthquake stricken area. METHODS: Case count,
      county's location, demographic, health, and social economics data were collected.
      Longitudinal multilevel model of extra-Poisson and spatial clustering analysis
      Besag and Newell's method were used. RESULTS: The incidence rate decreased from
      117.59 to 81.04/100,000, and the associated factors included time, latitude of
      the county, proportion of people aged no more than 29 years, and the disaster
      affected severity of the county. The temporal distribution of mortality rate was
      parabolic, with a summit in 2008. The associated factors included time, whether
      or not the county is minority inhabited area, and the disaster-affected severity
      of the county. Two clustered regions of incidence rate were detected with little
      variations before and after the quake, which were Aba-Ganzi region and Liangshan
      Leshan border region. The clustered regions of mortality rate detected were five
      counties located in Aba-Ganzi region in 2008, and no cluster was detected during
      other years. CONCLUSIONS: Tuberculosis epidemiology demonstrates a special spatio
      temporal distribution pattern. Wenchuan earthquake has effects especially on
      mortality rate. Natural, demographic, and social factors also contribute.

PMID- 24325372
TI  - Internal challenge to clinical trial project management: strategies for managing
      investigator compliance.
AB  - BACKGROUND: Managing compliance in a clinical research, especially in a multi
      centre randomized clinical trial (MRCT) is vital. We now feel the need to take a
      look at the once overlooked area of investigator compliance as it may provide
      resources necessary for producing satisfactory trial outcomes. OBJECTIVES: To
      analyze investigator performance and examine their adherence behavior using data
      collected and information gained from the MISPS-TCM, a Chinese national research
      project. METHODS: Four researchers were responsible for collecting relevant
      information and investigating the compliance behavior of participants in MISPS
      TCM. The Data Management Committee of MISPS-TCM offered us the number of
      withdrawal at each site and other site information. Reports on investigator
      compliance events were provided by the Monitoring Committee. Records of any
      misconduct of or errors made by the investigator were collected from the Center's
      daily management diary. Other information sources included trial managers and
      investigators at the Center or at different sites of the study. RESULTS:
      Investigator compliance can be an important determinant of trial outcomes and the
      degree of compliance may have detrimental effects on the reliability of findings
      of an MRCT, directly or indirectly. CONCLUSIONS: Trial managers of future MRCTs
      should take a firm grip on investigator compliance from the following aspects.
      First, physicians should be provided with more opportunities. Second, we created
      and recommended the 'Five Step Method' for evaluating investigators. Third,
      measures must be taken to secure investigator compliance. Fourth, evaluation of
      investigator compliance in an MRCT needs to be made.

PMID- 24325373
TI  - How do patients between the age of 65 and 75 use a web-based decision aid for
      treatment choice in localized prostate cancer?
AB  - OBJECTIVES: This study was designed to evaluate the use of a web-based decision
      aid by a 65plus patient group in their decision-making process for treatment of
      localized prostate cancer. Of particular interest was the use of technology
      features such as patients' statements, comparative tables, and a values
      clarification tool. METHODS: One hundred men from the University Hospital of
      Leuven campus, Gasthuisberg, were invited to use the web-based decision aid in
      their decision-making process. Twenty-six men were excluded based on non- or
      limited use of the decision aid. Of the remaining 74 men, user specifications,
      decision aid surfing characteristics by means of web-log data, and especially the
      use of technology features were analyzed. RESULTS: Men spent on average 30
      minutes on the web-based decision aid. Most time was spent on the pages with
      information on treatment options. These pages were also most frequently accessed.
      The use of the feature 'comparative tables' was the highest, followed by the
      'values clarification tool'. According to age (<70 or >70 years) differences were
      observed for the time spent on the decision aid, the pages accessed, and the use
      of the technology features. CONCLUSION: Despite concerns about the usability of a
      web-based decision aid for elderly patients, these results indicated that the
      majority of 65plus persons with good internet skills use a web-based decision aid
      as well as its incorporated technology features.

PMID- 24325374
TI  - Impact of pay-for-performance on management of diabetes: a systematic review.
AB  - OBJECTIVES: To review and synthesize published evidence of pay-for-performance
      (P4P) effects on management of diabetes. METHODS: Databases including Ovid
      MEDLINE, EMbase, PubMed, The Cochrane Library (Issue 3, 2012) were
      comprehensively searched for the effects of P4P programs in terms of patient
      outcomes and physician behaviors. Studies covering detailed data were included
      and synthesized. The quality of the body of evidence for each quality indicator
      was determined using Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) system. RESULTS: Among 742 identified articles, 12 interrupted
      time series studies, 7 controlled before-after studies, and 2 cross-sectional
      studies were included. Additionally, 12 studies were further included for
      quantitative analysis. Results of meta-analysis showed that P4P produced
      generally positive effects in most indicators (eg, patients with records of total
      cholesterol or blood pressure). However, these results were inconsistent. The
      percentage of patients with HbA1c <= 7% or 53 mmol/mol showed a pooled odds ratio
      of 0.98 in patients, but a pooled mean difference of 19.71% in the physician
      groups. The odds ratios of receiving tests/reaching an outcome level were also
      diverse in patients (odds ratios ranged from 0.98 to 3.32). Besides, process
      indicators had higher rates of improvement than outcome indicators. CONCLUSIONS:
      P4P programs have variable impacts on patient outcomes of diabetes as well as
      physician behaviors, with various effects from negligible to strongly beneficial.
      Considering the low quality of the included studies, this conclusion should be
      cautiously interpreted.

PMID- 24325376
TI  - The Cochrane database of systematic reviews - issue 7 2013.

PMID- 24325375
TI  - Adoptive infusion of tolerance dendritic cells prolongs survival of small
      intestine allografts in rats: systematic review and meta-analysis.
AB  - BACKGROUND: Postoperative infections and rejection are the main limiting factors
      of small intestine allograft survival. In this study, we performed a systematic
      review and meta-analysis to review rat small intestine allograft survival
      following infusion of tolerance dendritic cells (Tol-DCs) induced by different
      methods. METHODS: Relevant publications were searched from PubMed database and
      EMbase database. Meta-analysis was performed using RevMan 5.0 software. We chose
      allograft survival, mixed leukocyte reaction, Th1/Th2 differentiation, Treg
      induction, and cytotoxic T lymphocyte activity as the outcomes by which to
      examine possible mechanisms that promote survival. RESULTS: Eleven suitable
      articles were identified and assessed. Tol-DCs induced by four methods all
      prolonged allograft survival. The difference in survival time between the Tol-DC
      group and the control group was indicated by SMD as follows: drug intervention
      (SMD = 3.02, 95% CI 1.16 to 4.88, P = 0.001), gene modification (SMD = 2.43, 95%
      CI 1.77 to 3.10, P < 0.00001), imDC (SMD = 1.76, 95% CI 0.90 to 2.62, P <
      0.0001), cytokine induction (SMD = 1.68, 95% CI 0.40 to 2.96, P = 0.01). Tol-DCs
      were also synergistic with immunosuppressive drugs or costimulation inhibitors,
      but no immune tolerance was observed. A single-dose intravenous injection of
      5*10(6) to 6*10(6) Tol-DCs showed the highest allograft survival. Possible
      mechanisms included donor-specific T-cell hyporesponsiveness and Th2
      differentiation. CONCLUSIONS: Our results demonstrated that Tol-DCs induced by
      four methods prolong rat small intestine allograft survival. Intravenous infusion
      of 5*10(6) to 6*10(6) Tol-DCs was the optimum dose in rat small intestine
      transplantation. Immunosuppressive or costimulatory blockade was synergistic with
      Tol-DC on graft survival. Additional high-quality studies with larger sample
      sizes are needed to better investigate small intestinal graft longer term
      survival.

PMID- 24325377
TI  - Swimming training for asthma in children and adolescents aged 18 years and under.

PMID- 24325378
TI  - Topical herbal therapies for treating osteo-arthritis.

PMID- 24325379
TI  - Nebuliser systems for drug delivery in cystic fibrosis.

PMID- 24325380
TI  - Folic acid or folinic acid for reducing side effects of methotrexate for people
      with rheumatoid arthritis.

PMID- 24325381
TI  - Education section - the need for core outcome sets.

PMID- 24325382
TI  - Tacrolimus-loaded PLGA implants: in vivo release and ocular toxicity.
AB  - PURPOSE: To evaluate the in vivo release and ocular toxicity of a tacrolimus
      loaded PLGA intravitreal implant. METHODS: Tacrolimus-loaded PLGA implants were
      inserted into the vitreous cavity of rabbits' eye. At different time points, the
      vitreous was retrieved and the concentration of tacrolimus released from the
      implants was determined. Clinical examination was performed to evaluate the
      implant tolerance. RESULTS: PLGA implants provided controlled and prolonged
      release of tacrolimus. Approximately 99.97% of the drug was released from the
      devices at 6 weeks. Ophthalmic examination revealed no evidence of toxic effects
      of implants. CONCLUSIONS: Tolerance and feasibility of the tacrolimus-loaded PLGA
      implants, as sustained intraocular drug delivery systems, were demonstrated.

PMID- 24325384
TI  - Unexpected reactions of the anti-IgA antibody particle gel immunoassay.
AB  - BACKGROUND: The cause of allergic transfusion reactions remains often unknown,
      but in rare cases anti-immunoglobulin A (IgA) antibodies in patients with IgA
      deficiency can be found. We report on the use of the DiaMed particle gel
      immunoassay (PaGIA) for detection of anti-IgA antibodies in patients with
      allergic transfusion reactions. METHODS: The examination of the suspected adverse
      reactions included an anti-IgA antibody test (ID-PaGIA Anti-IgA antibody test;
      DiaMed GmbH, Cressier , Switzerland) and measurement of IgA concentration in the
      patient's plasma. In the case of a discrepancy IgA subclasses were examined and
      neutralization of the anti-IgA antibodies by pure IgA was performed. RESULTS: Of
      142 patients tested for IgA concentration and anti-IgA antibodies, 8 gave
      positive results for the anti-IgA antibody test. In seven of these cases (4.9% of
      the patients tested) IgA levels were found to be normal, and in four of five so
      tested, the positive result could not be neutralized with purified IgA. Only one
      patient had confirmed IgA deficiency with anti-IgA antibodies that were
      neutralized by addition of purified IgA. CONCLUSION: Cause and clinical relevance
      of a positive reaction of the anti-IgA antibody test in patients with normal
      total IgA and normal IgA subclasses remains unknown. Because of the high false
      positive rate we do not recommend this test as a screening test for anti-IgA
      antibodies when evaluating allergic transfusion reactions, but instead recommend
      measurement of total IgA in patient's plasma or serum as a primary screen for IgA
      deficiency with antibodies as a cause of allergic transfusion reaction.

PMID- 24325385
TI  - Paradoxical effects of anti-TNF-alpha agents in inflammatory diseases.
AB  - Anti-TNF agents represent a major breakthrough in the management of inflammatory
      diseases. Among the side effects of these agents are the so-called paradoxical
      effects described in this review. They represent new onset or exacerbation of a
      condition (symptom/disease), usually improved with TNF blockers. These
      paradoxical effects are mainly psoriasiform skin reactions, uveitis and
      granulomatous diseases (such as sarcoidosis and Crohn's disease). Infrequent and
      probably underreported, they should be discussed from the viewpoint of
      spontaneous features of the underlying disease (e.g., uveitis or psoriasis in a
      case of spondyloarthritis). The causal mechanism of occurrence is still a matter
      of debate, but may implicate an imbalance of cytokines toward interferons,
      chemokines and probably IL-17. These reactions may raise differential diagnosis
      problems. Symptoms resolve, most of the time, due to the discontinuation of the
      anti-TNF agent or sometimes a switch to another TNF blocker; but in some cases,
      it is a class effect that could lead to the withdrawal of all anti-TNF agents. 

PMID- 24325386
TI  - Carnitine for prevention of antituberculosis drug-induced hepatotoxicity: a
      randomized, clinical trial.
AB  - BACKGROUND AND AIM: In the present study, the potential benefits of oral
      carnitine in preventing antituberculosis drug-induced hepatotoxicity (ATDH) were
      evaluated. METHODS: Fifty-four patients in the carnitine and 62 patients in the
      placebo group completed the study. The carnitine group received 1000 mg oral
      carnitine solution twice daily for 4 weeks. The placebo group received 10 mL of
      oral placebo solution twice daily for 4 weeks. ATDH was defined as an increase in
      the serum level of aspartate aminotransferase or alanine aminotransferase greater
      than three or five times of the upper limit of normal with or without clinical
      symptoms of hepatotoxicity, respectively. RESULTS: During the study period, 29
      (25%) patients experienced ATDH. Among these patients, nine (16.7%) and 20
      (32.3%) were in the carnitine and placebo groups, respectively (P = 0.049). Based
      on multivariate logistic regression model, age over 35 years old (odds ratio [OR]
      = 7.01, P = 0.002), human immunodeficiency virus infection (OR = 40.4, P <
      0.001), diabetes mellitus (OR = 37.6, P = 0.001), and placebo treatment (OR =
      0.1, P = 0.01) were identified as predisposing factors for ATDH. CONCLUSION:
      Results of our preliminary clinical trial suggested that cotreatment with 2000 mg
      oral L-carnitine solution daily for 4 weeks significantly decreased the rate of
      ATDH.

PMID- 24325387
TI  - Dutch women in midwife-led care at the onset of labour: which pain relief do they
      prefer and what do they use?
AB  - BACKGROUND: Pain experienced during labour is more extreme than many other types
      of physical pain. Many pregnant women are concerned about labour pain and about
      how they can deal with this pain effectively.The aim of this study was to examine
      the associations among low risk pregnant women's characteristics and their
      preferred use and actual use of pain medication during labour. METHODS: Our study
      is part of the DELIVER study: a dynamic prospective multi-centre cohort study.
      The data for this study were collected between September 2009 and March 2011,
      from women at 20 midwifery practices throughout the Netherlands. Inclusion
      criteria for women were: singleton pregnancies, in midwife-led care at the onset
      of labour and speaking Dutch, English, Turkish or Arabic. Our study sample
      consisted of 1511 women in primary care who completed both questionnaire two
      (from 34 weeks of pregnancy up to birth) and questionnaire three (around six week
      post partum). These questionnaires were presented either online or on paper.
      RESULTS: Fifteen hundred and eleven women participated. Prenatally, 15.9% of
      women preferred some method of medicinal pain relief. During labour 15.2% of the
      total sample used medicinal pain relief and 25.3% of the women who indicated a
      preference to use medicinal pain relief during pregnancy, used pain medication.
      Non-Dutch ethnic background and planned hospital birth were associated with
      indicating a preference for medicinal pain relief during pregnancy. Primiparous
      and planned hospital birth were associated with actual use of the preferred
      method of medicinal pain relief during labour. Furthermore, we found that 85.5%
      of women who indicated a preference not to use pain medication prenatally, did
      not use any medication. CONCLUSIONS: Only a small minority of women had a
      preference for intrapartum pain medication prenatally. Most women did not receive
      medicinal pain relief during labour, even if they had indicated a preference for
      it.Care providers should discuss the unpredictability of the labour process and
      the fact that actual use of pain medication often does not match with women's
      preference prenatally.

PMID- 24325388
TI  - Cerebrovascular diseases in the elderly: the challenge of multiple aneurysms.
AB  - OBJECTIVE: The worldwide population aging and the nowadays medical advances
      impose to consider new management guidelines for elderly. Aim of this study was
      to assess the best treatment in elderly with multiple intracranial aneurysms
      (MIA). METHODS: From 1994 to 2011, we admitted 1462 patients with ruptured
      cerebral aneurysm. Among those aged >=65 years, 43 had MIA (15% of elderly). Size
      and aneurysm location, timing and type of treatment were analyzed. Patients were
      thus stratified according to Hunt-Hess grade on admission and evaluated at 6
      months using the Glasgow Outcome Scale (GOS). RESULTS: We had 87 aneurysms in the
      final series. Three patients died because of the impossibility to treat the
      ruptured aneurysm. No new bleeding from untreated aneurysms was observed; no
      retreatment after previous coiling was performed. CONCLUSIONS: MIA lead to
      significantly poorer outcomes, especially in elderly, because of their general
      clinical condition, presence of risk factors and lower capacity of reaction to
      stressful events. In patients without large hematomas, coiling of the ruptured
      aneurysm represents the procedure with high effectiveness. The clinical
      conditions on admission represent the most important factor for the treatment
      results. To reduce the treatment-related risks we do recommend a conservative
      approach for the unruptured aneurysms.

PMID- 24325389
TI  - Association between endothelial nitric oxide synthase gene polymorphism (T-786C)
      and ischemic stroke susceptibility: a meta-analysis.
AB  - BACKGROUND: The endothelial nitric oxide synthase (eNOS) T-786C polymorphism has
      been implicated in a number of studies investigating ischemic stroke (IS), yet
      previously published studies showed inconsistent results that recent meta
      analyses have not resolved. METHODS: In the comprehensive meta-analysis of 12
      association studies involving 2836 IS cases and 3354 control subjects, we used a
      more stringent inclusion method and summarized data on the association of eNOS T
      786C polymorphism and IS susceptibility. RESULTS: We found a significantly
      lowered IS risk under the CC vs. TT genetic model (odds ratio, OR = 0.53, 95%
      confidence interval, CI = 0.29-0.98, p = 0.160, I(2) = 45.5%) by random effects
      model in Caucasians and under the allele model C vs. T (OR = 0.42, 95% CI = 0.21
      0.87) by fixed effects model in African-Americans. In addition, a significant
      increased risk of IS was observed in Asians (C vs. T: OR = 1.14, 95% CI = 1.02
      1.28, p = 0.990, I(2) = 0.0%) by fixed effects model. Stratified analysis by mean
      age also showed that the allele C carriers, compared with the allele T allele
      carriers, had higher risk of suffering IS (OR = 1.16, 95% CI = 1.03-1.31) in the
      population of 60-65 years without heterogeneity. CONCLUSIONS: The combined
      results suggest that eNOS T-786C polymorphism may be associated with IS
      susceptibility among the population between 60 and 65 years in particular.

PMID- 24325390
TI  - Neuroprotective activity of L-theanine on 3-nitropropionic acid-induced
      neurotoxicity in rat striatum.
AB  - The present study has been designed to investigate the protective effect of L
      theanine against 3-nitropropionic acid (3-NP)-induced Huntington's disease (HD)
      like symptoms in rats. The present experimental protocol design includes systemic
      3-NP acid (10 mg/kg intraperitonially) treatment for 14 d. L-theanine (100 and
      200 mg/kg) was given orally, once a day, 1 h before 3-NP acid treatment for 14 d.
      Body weight and behavioral parameters (Morris water maze, open field test (OFT),
      forced swim test (FST) and rotarod activity) were assessed on 1st, 5th, 10th and
      15th day post-3-NP acid administration. Malondialdehyde (MDA), glutathione (GSH),
      superoxide dismutase (SOD) and catalase (CAT) levels and mitochondrial enzyme
      complex. Succinate dehydrogenase (SDH) were measured on the 15th day in the
      striatum. Systemic 3-NP acid treatment significantly reduced body weight,
      locomotor activity and oxidative defense. The mitochondrial enzyme activity was
      also significantly impaired in the striatum region in 3-NP acid-treated animals.
      L-theanine (100 and 200 mg/kg b.wt.) treatment significantly attenuated the
      impairment in behavioral, biochemical and mitochondrial enzyme activities as
      compared to the 3-NP acid-treated group. The results of the present study suggest
      that pretreatment with L-theanine significantly attenuated 3-NP induced oxidative
      stress and restored the decreased SOD, GSH, CAT and SDH activity. It also
      decreased the neuronal damage as evidenced by histopathological analysis of
      striatum. Based on the above study, it has been proved that L-theanine has
      neuroprotective activity against 3-NP induced neurotoxicity.

PMID- 24325391
TI  - SbHKT1;4, a member of the high-affinity potassium transporter gene family from
      Sorghum bicolor, functions to maintain optimal Na+ /K+ balance under Na+ stress.
AB  - In halophytic plants, the high-affinity potassium transporter HKT gene family can
      selectively uptake K+ in the presence of toxic concentrations of Na+. This has so
      far not been well examined in glycophytic crops. Here, we report the
      characterization of SbHKT1;4, a member of the HKT gene family from Sorghum
      bicolor. Upon Na+ stress, SbHKT1;4 expression was more strongly upregulated in
      salt-tolerant sorghum accession, correlating with a better balanced Na+ /K+ ratio
      and enhanced plant growth. Heterogeneous expression analyses in mutants of
      Saccharomyces cerevisiae and Arabidopsis thaliana indicated that overexpressing
      SbHKT1;4 resulted in hypersensitivity to Na+ stress, and such hypersensitivity
      could be alleviated with the supply of elevated levels of K+, implicating that
      SbHKT1;4 may mediate K+ uptake in the presence of excessive Na+. Further
      electrophysiological evidence demonstrated that SbHKT1;4 could transport Na+ and
      K+ when expressed in Xenopus laevis oocytes. The relevance of the finding that
      SbHKT1;4 functions to maintain optimal Na+ /K+ balance under Na+ stress to the
      breeding of salt-tolerant glycophytic crops is discussed.

PMID- 24325393
TI  - Parasitic worms and allergies in childhood: insights from population studies 2008
      2013.
AB  - The last few decades have seen a marked increase in the global prevalence of
      allergic diseases particularly among children. Among the factors attributed to
      this rise has been reduced exposure to pathogens during childhood leading to
      insufficient maturation of the regulatory arm of developing immune systems. Over
      the years, a number of epidemiological studies have observed an inverse
      relationship between parasitic worm (helminth) infections and allergies. The
      purpose of this review is to highlight insights from population studies conducted
      among children published between 2008 and 2013 that explore the complex dynamics
      between helminth infections and allergies. These insights include the effect of
      anthelmintic treatment on allergic responses, an elucidation of immune mechanisms
      and an examination of helminth-induced immunoglobulin E cross-reactivity. A
      better understanding of the relationship between helminths and allergies is
      imperative as research directions move toward harnessing the therapeutic
      potential of helminths and their products in the treatment of allergic disorders.

PMID- 24325392
TI  - Reduced tumorigenicity and pathogenicity of cervical carcinoma SiHa cells
      selected for resistance to cidofovir.
AB  - BACKGROUND: Insights into the mechanisms associated with chemotherapy-resistance
      are important for implementation of therapeutic strategies and for unraveling the
      mode of action of chemotherapeutics. Although cidofovir (CDV) has proven
      efficacious in the treatment of human papillomavirus (HPV)-induced proliferation,
      no studies concerning the development of resistance to CDV in HPV-positive tumor
      cells have been performed yet. METHODS: From the cervical carcinoma SiHa cells
      (SiHaparental), which are HPV-16 positive, cidofovir-resistant cells (SiHaCDV)
      were selected, and differential gene expression profiles were analyzed by means
      of microarrays. We examined in vitro phenotyping of resistant cells compared to
      parental cells as well as tumorigenicity and pathogenicity in a mouse-xenograft
      model. RESULTS: SiHaCDV had a resistant phenotype and a reduced growth both in
      vitro and in vivo. A markedly diminished inflammatory response (as measured by
      production of host- and tumor-derived cytokines and number of neutrophils and
      macrophages in spleen) was induced by SiHaCDV than by SiHaparental in the
      xenograft model. Gene expression profiling identified several genes with
      differential expression upon acquisition of CDV-resistance and pointed to a
      diminished induction of inflammatory response in SiHaCDV compared to
      SiHaparental. CONCLUSIONS: Our results indicate that acquisition of resistance to
      cidofovir in SiHa cells is linked to reduced pathogenicity. The present study
      contributes to our understanding on the antiproliferative effects of CDV and on
      the mechanisms involved, the inflammatory response playing a central role.

PMID- 24325394
TI  - The aryl hydrocarbon receptor antagonist StemRegenin 1 promotes human
      plasmacytoid and myeloid dendritic cell development from CD34+ hematopoietic
      progenitor cells.
AB  - The superiority of dendritic cells (DCs) as antigen-presenting cells has been
      exploited in numerous clinical trials, where generally monocyte-derived DCs (Mo
      DCs) are injected to induce immunity in patients with cancer or infectious
      diseases. Despite promising expansion of antigen-specific T cells, the clinical
      responses following vaccination have been limited, indicating that further
      improvements of DC vaccine potency are necessary. Pre-clinical studies suggest
      that vaccination with combination of primary DC subsets, such as myeloid and
      plasmacytoid blood DCs (mDCs and pDCs, respectively), may result in stronger
      clinical responses. However, it is a challenge to obtain high enough numbers of
      primary DCs for immunotherapy, since their frequency in blood is very low. We
      therefore explored the possibility to generate them from hematopoietic progenitor
      cells (HPCs). Here, we show that by inhibiting the aryl hydrocarbon receptor with
      its antagonist StemRegenin 1 (SR1), clinical-scale numbers of functional
      BDCA2(+)BDCA4(+) pDCs, BDCA1(+) mDCs, and BDCA3(+)DNGR1(+) mDCs can be
      efficiently generated from human CD34(+) HPCs. The ex vivo-generated DCs were
      phenotypically and functionally comparable to peripheral blood DCs. They secreted
      high levels of pro-inflammatory cytokines such as interferon (IFN)-alpha,
      interleukin (IL)-12, and tumor necrosis factor (TNF)-alpha and upregulated co
      stimulatory molecules and maturation markers following stimulation with Toll-like
      receptor (TLR) ligands. Further, they induced potent allogeneic T-cell responses
      and activated antigen-experienced T cells. These findings demonstrate that SR1
      can be exploited to generate high numbers of functional pDCs and mDCs from
      CD34(+) HPCs, providing an alternative option to Mo-DCs for immunotherapy of
      patients with cancer or infections. 

PMID- 24325395
TI  - The singular qualities of motor neurones in health and disease.

PMID- 24325396
TI  - Effect of dynamic random leaks on the monitoring accuracy of home mechanical
      ventilators: a bench study.
AB  - BACKGROUND: So far, the accuracy of tidal volume (VT) and leak measures provided
      by the built-in software of commercial home ventilators has only been tested
      using bench linear models with fixed calibrated and continuous leaks. The
      objective was to assess the reliability of the estimation of tidal volume (VT)
      and unintentional leaks in a single tubing bench model which introduces random
      dynamic leaks during inspiratory or expiratory phases. METHODS: The built-in
      software of four commercial home ventilators and a fifth ventilator-independent
      ad hoc designed external software tool were tested with two levels of leaks and
      two different models with excess leaks (inspiration or expiration). The external
      software analyzed separately the inspiratory and expiratory unintentional leaks.
      RESULTS: In basal condition, all ventilators but one underestimated tidal volume
      with values ranging between -1.5 +/- 3.3% to -8.7% +/- 3.27%. In the model with
      excess of inspiratory leaks, VT was overestimated by all four commercial software
      tools, with values ranging from 18.27 +/- 7.05% to 35.92 +/- 17.7%, whereas the
      ventilator independent-software gave a smaller difference (3.03 +/- 2.6%). Leaks
      were underestimated by two applications with values of -11.47 +/- 6.32 and -5.9
      +/- 0.52 L/min. With expiratory leaks, VT was overestimated by the software of
      one ventilator and the ventilator-independent software and significantly
      underestimated by the other three, with deviations ranging from +10.94 +/- 7.1 to
      -48 +/- 23.08%. The four commercial tools tested overestimated unintentional
      leaks, with values between 2.19 +/- 0.85 to 3.08 +/- 0.43 L/min. CONCLUSIONS: In
      a bench model, the presence of unintentional random leaks may be a source of
      error in the measurement of VT and leaks provided by the software of home
      ventilators. Analyzing leaks during inspiration and expiration separately may
      reduce this source of error.

PMID- 24325397
TI  - Drainage of a thin liquid film between hydrophobic spheres: boundary curvature
      effects.
AB  - We investigate theoretically the drainage of a thin liquid film confined between
      two hydrophobic spheres. Such a problem has been considered in Vinogradova's
      seminal work, emphasizing the role of slippage. However, it does not include the
      boundary curvature effects, which may become especially important when the slip
      lengths are comparable to the sphere radii. We present a reformulation of the
      hydrodynamic boundary conditions, with the boundary curvature effects fully taken
      into account. It is shown that such effects not only renormalize the effective
      slip lengths but also give new contributions to the pressure and drag force,
      neglected so far. We focus on the symmetric case of two identical spheres with
      the same radii and slip lengths and obtain analytical expressions for the
      pressure as well as the drag force. The boundary curvature corrections to the
      drag force are analyzed and found to be more important for more hydrophobic
      spheres. The implications of our results are discussed for the coagulation
      processes of colloids and measurements of surface forces or slip lengths with the
      drainage technique. 

PMID- 24325398
TI  - Acetone cataluminescence as an indicator for evaluation of heterogeneous base
      catalysts in biodiesel production.
AB  - Rapid and effective evaluation techniques for heterogeneous base catalysts in
      biodiesel production are highly desirable with increased global demand for
      biofuels. In this work, we have discovered direct connections between the number
      of medium-strength basic sites of heterogeneous base catalysts in biodiesel
      production and cataluminescence intensity in acetone aldol condensation
      reactions. Accordingly, acetone cataluminescence has been employed as an
      indicator for rapid evaluation of heterogeneous base catalysts in biodiesel
      production. Its practical feasibility has been first established using
      commercially available heterogeneous base catalysts in biodiesel production
      (including MgO, Al2O3, TiO2, and ZnO), indicating a good matching between the
      proposed cataluminescence screening method and routine temperature-programmed
      desorption measurements. Subsequently, the proposed cataluminescence method can
      be used to effectively distinguish a set of layered double hydroxides and layered
      double oxide with fewer differences of basic sites, and the relative standard
      deviation (RSD) of the proposed method is 2.90%. The developed cataluminescence
      platform is able to take advantage of low cost, simple configuration, fast
      response, long-term stability, and easy operation. This work has a great
      potential in distinguishing weak/strong basic sites and even acidic sites of each
      catalyst system by tuning molecular probes. 

PMID- 24325400
TI  - Assessment of body composition by dual-energy X-ray absorptiometry, bioimpedance
      analysis and anthropometrics in children: the Physical Activity and Nutrition in
      Children study.
AB  - OBJECTIVE AND METHODS: We compared InBody720 segmental multifrequency
      bioimpedance analysis (SMF-BIA) with Lunar Prodigy Advance dual-energy X-ray
      absorptiometry (DXA) in assessment of body composition among 178 predominantly
      prepubertal children. Segmental agreement analysis of body compartments was
      carried out, and inter-relationships of anthropometric and other measures of body
      composition were defined. Moreover, the relations of different reference criteria
      for excess body fat were evaluated. RESULTS: The prevalence of excess body fat
      varies greatly according to the used criteria. Intraclass and Pearson's
      correlations between SMF-BIA and DXA were >0.92 in total body and >0.74 in
      regional measures. SMF-BIA underestimated percentage body fat (%BF) and fat mass
      (FM), and overestimated lean mass (LM) and percentage LM with significant offset
      trend bias. Higher adiposity increased offsets, and overall agreement was poorer
      in girls. On average, %BF offsets (girls/boys) and limits of agreement (LA) were
      3.9/1.6% [(-)1.4-9.2%/(-)3.4-6.7%]. Interestingly percentage offsets of fat
      content (%BF: 18.9/10.1%, FM: 18.8/11.1%) showed no significant bias trends
      indicating that the corresponding absolute methodological offset depends on the
      amount of fat content. The smallest percentage offset was found with LM:
      4.3/0.1%, referring offset (LA) of 0.88/0.03 kg (+/-2.05/+/-1.71 kg).
      Correspondingly, segmental LM had poorer agreement than total body LM. All
      anthropometrics except for the waist-to-hip ratio showed strong correlations (r =
      0.76-0.95) with abdominal and total body fat. CONCLUSION: Segmental
      multifrequency bioimpedance analysis is precise enough for total-LM analysis and
      had also sufficient trueness for total body composition analysis to be used in
      epidemiological purposes. There is need to generate scientifically and clinically
      relevant criteria and reference values for excess body fat.

PMID- 24325399
TI  - Meta-selective C-H functionalization using a nitrile-based directing group and
      cleavable Si-tether.
AB  - A nitrile-based template that enables meta-selective C-H bond functionalization
      was developed. The template is applicable to a range of substituted arenes and
      tolerates a variety of functional groups. The directing group uses a silicon atom
      for attachment, allowing for a facile introduction/deprotection strategy
      increasing the synthetic practicality of this template. 

PMID- 24325401
TI  - Distinct regions of triadin are required for targeting and retention at the
      junctional domain of the sarcoplasmic reticulum.
AB  - Ca2+ release, which is necessary for muscle contraction, occurs at the j-SR
      (junctional domain of the sarcoplasmic reticulum). It requires the assembly of a
      large multiprotein complex containing the RyR (ryanodine receptor) and additional
      proteins, including triadin and calsequestrin. The signals which drive these
      proteins to the j-SR and how they assemble to form this multiprotein complex are
      poorly understood. To address aspects of these questions we studied the
      localization, dynamic properties and molecular interactions of triadin. We
      identified three regions, named TR1 (targeting region 1), TR2 and TR3, that
      contribute to the localization of triadin at the j-SR. FRAP experiments showed
      that triadin is stably associated with the j-SR and that this association is
      mediated by TR3. Protein pull-down experiments indicated that TR3 contains
      binding sites for calsequestrin-1 and that triadin clustering can be enhanced by
      binding to calsequestrin-1. These findings were confirmed by FRET experiments.
      Interestingly, the stable association of triadin to the j-SR was significantly
      decreased in myotubes from calsequestrin-1 knockout mice. Taken together, these
      results identify three regions in triadin that mediate targeting to the j-SR and
      reveal a role for calsequestrin-1 in promoting the stable association of triadin
      to the multiprotein complex associated with RyR. 

PMID- 24325402
TI  - Growth factor release from polyelectrolyte-coated titanium for implant
      applications.
AB  - Polyelectrolyte multilayer coatings based on poly(methacrylic acid) and poly-l
      histidine were formed on anodized titanium surfaces with adsorbed bone
      morphogenetic protein 2 (BMP-2) or basic fibroblast growth factor (FGFb). These
      coatings are proposed for use on titanium implanted devices. Coatings were
      capable of sustained release of growth factor over 25 days, with BMP-2 and FGFb
      exhibiting approximately identical release profiles. Cell culture on growth
      factor-eluting surfaces was more effective for preosteoblasts on BMP-2-eluting
      surfaces than for fibroblasts on FGFb-eluting surfaces. Cell counts at all time
      points on BMP-2-eluting surfaces were significantly higher than for those on
      anodized titanium or polyelectrolyte surfaces that did not contain BMP-2.
      Alkaline phosphatase levels were significantly higher after 21 days on BMP-2
      eluting surfaces, indicating increased bone growth. 

PMID- 24325403
TI  - Long-term obesity prevention and the Motivating Adolescents with Technology to
      CHOOSE HealthTM program.
AB  - BACKGROUND: The Motivating Adolescents with Technology to CHOOSE HealthTM (MATCH)
      intervention integrates lifestyle behavior change curriculum within academic
      subjects taught in seventh grade. This study assesses obesity prevention in
      participants into high school. METHODS: The study compares four- to five-year
      longitudinal data from a single-site cohort (N=106, 54% retained from 195
      participants at baseline; 82% of those still at the school) pre- and
      postintervention in a rural middle school with high obesity rates with data from
      the 2006 Child Survey and 2010 Child and Young Adult Surveys from the National
      Longitudinal Survey of Youth 1979 (N=600), which serves as a nationally
      representative comparison group. Outcome measures include pre- and postchanges in
      weight category, BMI, BMI z-score, BMI percentile for age and gender, and rates
      of change per month in BMI measures. RESULTS: At follow-up, change in percent
      overweight was significantly different between groups, with the MATCH group
      decreasing (20-12%) and the comparison group increasing (17-19%). Overall, the
      MATCH group had significantly higher decrease rates in BMI z-scores (p=0.002) and
      BMI percentile (p=0.01) than the comparison group. Of all adolescents at healthy
      weight at baseline, 2% from MATCH became overweight after five years, whereas 13%
      of the comparison group increased to overweight or obese (p=0.02) after four
      years. CONCLUSIONS: Despite a small sample size and a high-risk setting, at long
      term follow-up, a greater proportion of MATCH participants than in the comparison
      group decreased from overweight to healthy weight or remained at healthy weight.
      The MATCH results suggest that some proportion of high-risk adolescents can have
      their growth trajectory follow a healthier path than expected.

PMID- 24325404
TI  - Emerging roles for triggering receptor expressed on myeloid cells receptor family
      signaling in inflammatory diseases.
AB  - Innate immune receptors represent important therapeutic targets for inflammatory
      disorders. In particular, the Toll-like receptor (TLR) family has emerged as a
      promoter of chronic inflammation that contributes to obesity, insulin resistance
      and atherosclerosis. Importantly, triggering receptor expressed on myeloid cells
      1 (TREM-1) has been characterized as an 'amplifier' of TLR2 and TLR4 signaling.
      TREM-1- and TREM-2-dependent signaling, as opposed to TREM-like transcript-1 (TLT
      1 or TREML1), are mediated through association with the transmembrane adaptor
      DNAX activation protein of 12 kDa (DAP12). Recessive inheritance of rare
      mutations in DAP12 or TREM-2 results in a disorder called polycystic
      lipomembranous osteodysplasia with sclerosing leukoencephalopathy, and
      surprisingly these subjects are not immunocompromised. Recent progress into the
      roles of TREM/DAP12 signaling is critically reviewed here with a focus on
      metabolic, cardiovascular and inflammatory diseases. The expanding repertoire of
      putative ligands for TREM receptors is also discussed. 

PMID- 24325405
TI  - Role of IL28B for chronic hepatitis C treatment toward personalized medicine.
AB  - Genome-wide association studies recently revealed that certain interleukin-28B
      (IL28B) polymorphisms are strongly associated with responses to pegylated
      interferon (PEG-IFN) and ribavirin (RBV) therapy in patients chronically infected
      with hepatitis C virus (HCV) genotype 1, as well as with spontaneous clearance of
      HCV. Subsequent reports revealed that IL28B genotypes also affect treatment
      efficacy in chronic infection with other HCV genotypes. Furthermore, there have
      been several reports that implicate IL28B genotypes in inflammatory status,
      progression of fibrosis and adverse clinical outcomes in chronic hepatitis C
      (CHC). Therapy of CHC recently entered a new era with the deployment of direct
      acting antivirals. These include nonstructural 3/4A protease inhibitors which
      have shown promise in combination with PEG-IFN/RBV in several clinical trials.
      IFN-free therapy is expected to be useful especially in IFN-resistant patients
      and may become the standard of care in the future. Several clinical trials have
      revealed an association between IL28B genotype and treatment efficacy in triple
      therapy or IFN-free regimens. On the other hand the mechanism of the effect of
      IL28B on HCV infection has not yet been elucidated. Recently, it was shown that
      the polymorphism of IFN-lambda 4 (IFNL4) is in high linkage disequilibrium with
      that of near IL28B, and more strongly associated with spontaneous or treatment
      induced HCV clearance than IL28B genotypes, especially in individuals of African
      ancestry. This finding provides new insights into the genetic regulation of HCV
      clearance and its clinical management. IL28B genotyping will be also useful for
      personalized CHC treatment in the forthcoming era of direct-acting antivirals. 

PMID- 24325406
TI  - Farinose flavonoids are associated with high freezing tolerance in fairy primrose
      (Primula malacoides) plants.
AB  - The deposition of surface (farinose) flavonoids on aerial parts of some Primula
      species is a well-documented but poorly understood phenomenon. Here, we show that
      flavonoid deposition on the leaves and winter buds may contribute strongly to
      preventing freezing damage in these plants. The ice nucleation temperature of
      fairy primrose (Primula malacoides) leaves covered with natural flavone was
      approximately 6  degrees C lower compared to those that had their flavone
      artificially removed. Additionally, farinose flavonoids on the leaves reduced
      subsequent electrolyte leakage (EL) from the cells exposed to freezing
      temperatures. Interestingly, exogenous application of flavone at 4 mg/g fresh
      weight to P. malacoides leaves, which had the original flavone mechanically
      removed, restored freezing tolerance, and diminished EL from the cells to
      pretreatment values. Our results suggest that farinose flavonoids may function as
      mediators of freezing tolerance in P. malacoides, and exogenous application of
      flavone could be used to reduce freezing damage during sudden but predictable
      frost events in other plant species. 

PMID- 24325407
TI  - Trends of risk classification and primary therapy for Japanese patients with
      prostate cancer in Nara Uro-Oncological Research Group (NUORG)--a comparison
      between 2004-2006 and 2007-2009.
AB  - BACKGROUND: To assess the trends of risk classification and primary therapy in
      Japanese patients who were diagnosed with prostate cancer between 2004-2006 and
      2007-2009. METHODS: A total of 4752 patients who were newly diagnosed with
      prostate cancer at Nara Medical University and its 23 affiliated hospitals
      between 2004 and 2009 were enrolled. The differences in risk classification and
      primary therapy were compared in patients who were newly diagnosed between 2004
      2006 (prior period) and 2007-2009 (latter period). RESULTS: The proportion of
      patients with a high or greater risk significantly decreased in the latter period
      compared to the prior period (p < 0.001). The proportion of primary androgen
      deprivation therapy (PADT) was 50% in the prior period, and 40% in the latter
      period. On the other hand, the proportion of radiation therapy was 14% in the
      prior period, but 24% in the latter period. The proportion of radical
      prostatectomy was the same in the two periods (30%). The primary therapy was
      significantly different between the two periods (p < 0.001). CONCLUSIONS: Higher
      risk patients significantly decreased in the latter period compared to the prior
      period. The use of PADT also significantly decreased in the latter period.
      However, there were still higher risk patients in Japan, and the use of PADT was
      still common in patients with localized prostate cancer or locally advanced
      prostate cancer in Japan.

PMID- 24325408
TI  - Periorbital dermatitis in 4779 patients - patch test results during a 10-year
      period.
AB  - BACKGROUND: The thinness of the periorbital skin may facilitate allergen
      penetration, making this area particularly susceptible to sensitization. MATERIAL
      AND METHODS: For the cross-sectional study, data were collected by the 57
      participating centres of the Information Network of Departments of Dermatology. A
      total of 101 403 patients patch tested between January 2001 and December 2010
      were included. Of these, 4779 patients suffered from periorbital dermatitis.
      RESULTS: Two major subgroups with different general epidemiological data and
      sensitization to specific allergens have to be considered: (i) young females with
      increased rates of skin atopy and allergies, particularly from cosmetic and skin
      care products; and (ii) older subjects with allergy to topical medications. The
      prevalence of sensitization to ophthalmic allergens is generally less than that
      to environmental allergens. CONCLUSIONS: Allergic contact dermatitis is a leading
      cause of periorbital dermatitis. Patch testing should be considered in all
      patients with periorbital dermatitis when contact allergy is suspected, in order
      to identify and avoid offending allergens.

PMID- 24325409
TI  - Leporacarus gibbus infestation in client-owned rabbits and their owner.
AB  - BACKGROUND: Leporacarus gibbus is a fur mite infesting both laboratory and pet
      rabbits; infestation is usually subclinical, but in some instances it has been
      associated with a highly pruritic dermatitis. A zoonotic potential has also been
      suggested. ANIMALS: Two pet rabbits, living in the same household, were presented
      with moderate scaling, erythema, pruritus and alopecia. In both rabbits, the
      lesions were mainly localized around the neck. A pruritic papular dermatitis was
      also present on the owner's arms and legs. METHODS AND RESULTS: Parasitological
      examination of the rabbits' skin and fur revealed many mites of the species L.
      gibbus. Skin cytology and fungal culture were both negative for bacteria and
      fungi. Both rabbits were treated with a single application of a spot-on
      formulation of 1% moxidectin and 10% imidacloprid, as well as environmental
      disinfection with a miticide. After treatment, the rabbits improved markedly, and
      the lesions on the owner's arms and legs disappeared within a week. CONCLUSIONS
      AND CLINICAL IMPORTANCE: This is the second description of L. gibbus dermatitis
      in people. In the present case report, the lesions on the rabbits and their owner
      were very similar, a pruritic dermatitis with small papules, more evident on the
      owner's extremities. Due to its zoonotic potential, although uncommon, L. gibbus
      infestation should be considered as a possible differential in pet rabbits,
      particularly when owners have a papular eruption.

PMID- 24325410
TI  - Editorial for issue 4 of 2013, Journal of Evidence Based Medicine.

PMID- 24325411
TI  - Work of the Cochrane Bone, Joint and Muscle Trauma Review Group: making sense of
      complexity.
AB  - This article examines the ways in which members of the Cochrane Bone, Joint and
      Muscle Trauma Review Group have tackled the intrinsic complexity of a large
      clinical area. This features a diversity of injuries in people of all ages,
      predominantly physical and surgical interventions that are inherently complex
      interventions, and a huge array of outcome measures. The methods described
      include a purposeful focus on common injuries, such as fragility fractures in
      older people; and the generation of groups of "all intervention" reviews whose
      structure is informed by a systematic approach, incorporating knowledge of
      clinical pathways and categorization of interventions. The article concludes with
      some thoughts about the challenges ahead, particularly in terms of selecting the
      scopes of future reviews. 

PMID- 24325412
TI  - The Cochrane tobacco addiction group.
AB  - The Cochrane Tobacco Addiction Group produces up-to-date systematic reviews of
      interventions for the cessation and prevention of tobacco use. Many of our
      Cochrane Reviews have also been published in scientific journals. Our review
      prioritization schedule is informed by our group's experience and expertise as
      well as identifying topics for reviews via regular searches of current scientific
      literature and from other news sources, such as the Action on Smoking and Health
      updates. The Cochrane Register of Studies allows identification of new trials,
      which might be eligible for review updates. Everyday challenges include timely
      publishing and updating of our reviews, and ensuring compliance to Cochrane
      methodological expectations of Cochrane intervention review standards. We are
      grateful for the contributions of our authors and peer reviewers, with whom we
      aim to have close working and productive relationships. We look forward to
      continuing our contribution toward a reliable evidence base on interventions to
      combat tobacco addiction. 

PMID- 24325413
TI  - Cochrane Consumers and Communication Review Group: leading the field on health
      communication evidence.
AB  - This paper presents an overview of the history and achievements of the Cochrane
      Consumers and Communication Review Group, part of the international Cochrane
      Collaboration. It surveys the Group's establishment and structure, the scope of
      its Cochrane Reviews and the growth in its publication output over its 16-year
      history. The paper examines the Group's developmental work in interventions and
      outcomes related to patient communication and involvement, as well as
      methodological resources for review authors. It also outlines the Review Group's
      research partnerships with state, national and international agencies,
      particularly in the areas of chronic disease management, medicines use, public
      involvement, and vaccines communication. The Group's strong contribution to an
      evidence-base for health communication and participation are acknowledged. 

PMID- 24325414
TI  - Cochrane systematic reviews in the field of addiction: past and future.
AB  - BACKGROUND AND OBJECTIVE: The Cochrane Drugs and Alcohol Group aims to produce,
      update, and disseminate systematic reviews on the prevention, treatment, and
      rehabilitation of problematic drug and alcohol use. This paper describes what the
      Group has done since the 1990s to produce evidence to guide policy, practice, and
      research. METHOD: We analyze the coverage of topics by our reviews, the body of
      studies they have included, and the evidence produced. RESULTS: By July 2013, the
      Group had published 67 reviews, with 376 authors from 25 different countries.
      These reviews included 906 studies, of 3061 studies considered for inclusion.
      Most (90%) included studies were randomized trials. Considering the 'Implications
      for practice' section of each review, 41% interventions were classified as 'do
      it', 15% as 'do not do', and 44% as 'do only in research'. These proportions
      varied according to the type of substance of abuse studied. The proportion of 'do
      it' interventions were 46% for alcohol, 40% for opioids, 20% for
      psychostimulants, 40% for polydrugs, and 62% for prevention. CONCLUSION: Cochrane
      Reviews produced by the Drugs and Alcohol Group provide evidence on the
      effectiveness of several interventions, and identify areas of uncertainty where
      new research is needed.

PMID- 24325415
TI  - Finding and filling the gaps in the evidence with high quality clinical trials -
      the experience of one Cochrane Review Group.
AB  - The Cochrane Cystic Fibrosis and Genetic Disorders Group publishes systematic
      reviews of randomized trials for many genetic disorders. Given the rarity of
      these disorders, there are often few relevant trials to be included. Therefore,
      it is common for the reviews to be 'empty' and unable to present evidence which
      aids decision-making in clinical practice. However, we do not regard this as
      negative; rather we see this as a challenge and an opportunity to influence the
      research agenda. We have several reviews which clearly illustrate the cycle of
      assessing the evidence base, identifying the lack of data, generating high
      quality research and incorporating the resulting data into the original
      systematic review. 

PMID- 24325416
TI  - Systematic reviews: work that needs to be done and not to be done.
AB  - Systematic reviews are researches requiring great attention to detail. They may
      well necessitate considerable investment of effort to ensure relevant data are
      identified, extracted, synthesized, written up and disseminated. These tasks have
      already been greatly refined and, in some cases, simplified, by machines. The
      last two decades have seen remarkable progress in machine-assisted production of
      reviews - the next two should see much more. 

PMID- 24325417
TI  - The Cochrane Skin Group: a vanguard for developing and promoting evidence-based
      dermatology.
AB  - AIM: The Cochrane Skin Group (CSG) is part of the international Cochrane
      Collaboration (http://www.cochrane.org/). The CSG prepares, maintains and
      disseminates high quality evidence-based summaries on the prevention, diagnosis
      and treatment of skin diseases. We present a synopsis of the history, scope and
      priorities of the CSG. In addition, we report outcomes of CSG reviews and
      critically assess clinical value. METHODS: Descriptive analysis of systematic
      reviews published by the CSG since its inception including output, impact factor,
      associated methodological studies, and influence in clinical guidelines,
      promoting patient and public engagement and in triggering new primary research.
      RESULTS: The CSG started in 1997, and has published 61 reviews, 34 protocols and
      31 registered titles by August 2013. The CSG scope includes 1000 skin diseases;
      80% of reviews cover the top ten diagnoses and 40% of reviews provide clear
      guidance for clinical practice. CSG reviews had an impact factor of 6.1 in 2011
      which places it alongside top dermatology journals. CSG reviews are typically
      broad in focus and have been shown to be of better quality than non-Cochrane
      reviews. They are highly cited in clinical guidelines. Several reviews have
      identified evidence gaps that have led to better primary research. CONCLUSIONS:
      The CSG has emerged as a vanguard of evidence-based dermatology by growing a
      community interested in applying best external evidence to the care of skin
      patients and by identifying topics for research. CSG reviews are high impact,
      clinically relevant and have tangibly influenced international dermatology
      clinical practice guidelines and new research.

PMID- 24325418
TI  - Quality of reporting clinical trials published in five leading Sri Lankan medical
      journals.
AB  - OBJECTIVES: To assess the quality of reporting of clinical trials published in
      five leading Sri Lankan medical journals. METHODS: Six medical journals were hand
      searched for clinical trials published from 1982 to 2011. Eligible criteria were
      all randomized and non-randomized clinical trials conducted in humans. A
      checklist was developed based on CONSORT and TREND recommendations. Each study
      was independently evaluated by two reviewers. Outcome measures were presence of
      checklist items in published reports. RESULTS: Fifteen randomized and 24 non
      randomized parallel group trials from 724 studies in five journals met the
      inclusion criteria. Out of 39 trials, 39 (97%) clearly described the objectives,
      16 (41%) defined the periods of recruitment, 7 (18%) reported how sample size was
      determined, 10 (25.6%) reported the methods to enhance the quality of
      measurements, 20 (51%) reported baseline demographic and clinical characteristics
      of each group, 4 (10%) showed flow diagrams, 23 (69%) reported statistical
      methods used to compare groups for primary outcomes, 21 (54%) reported effect
      size, 4 (10%) reported its precision, and 20 (51%) interpreted the results in the
      context of current evidence, and 5 (13%) described the generalizability of the
      findings. Of the 15 randomized trials, only one (7%) reported sequence
      generation, 5 (33%) allocation concealment, 9 (60%) reported blinding status of
      participants or investigators, and 2 (13%) reported intention to treat analysis.
      CONCLUSIONS: Reporting of several essential recommendations remained suboptimal.
      Education and training of trial methods and awareness of the CONSORT and TREND
      statements and more attention to the quality of reporting may improve matters.

PMID- 24325419
TI  - Adoptive transfusion of tolerant dendritic cells prolong the survival of renal
      allografts: a systematic review.
AB  - OBJECTIVE: The aim of this study was to systematically review the effects of
      transfusing Tol-DCs induced by different methods on renal transplantation and
      survival time. METHOD: PubMed and EMbase were searched for relevant articles from
      inception to July 20(th), 2013. Renal allograft survival time was regarded as the
      endpoint outcome. The effects of Tol-DCs on renal transplantation were evaluated
      semi-quantitatively. RESULTS: Sixteen articles were included. There were three
      sources of Tol-DCs, including bone marrow, spleen, and thoracic duct lymph node.
      Rats were administrated cells intravenously and 83% of mice through the portal
      vein. Four subtypes of bone marrow Tol-DCs enhanced renal allograft time:
      immature DCs enhanced allograft survival 4.9-fold in rats and 2.0-fold in mice,
      gene modified DCs enhanced allograft survival 4.4-fold in rats and 2.2-fold in
      mice, and drug and cytokine induced enhanced allograft survival 2.9-fold and 2.7
      fold, respectively, in rats. Tol-DCs from the spleen and thoracic duct lymph
      nodes prolonged allograft survival 2.7-fold and 1.8-fold, respectively, in rats.
      1-2 * 10(6) doses of Tol-DCs extended the survival time of rats following renal
      transplantation. The key mechanisms by which Tol-DCs enhance allograft and
      overall survival included: (i) inducing T-cell hyporeactivity; (ii) reducing the
      effects of cytotoxic lymphocytes; and (iii) inducing Th2 differentiation.
      CONCLUSION: Bone marrow Tol-DCs can extend allograft survival and induce immune
      tolerance in fully MHC-mismatched renal transplantation in rats and mice. The
      effects of imDCs and gene modified Tol-DCs in mice are less marked. In
      conclusion, a single-injection of 1-2 * 10(6) doses of bone marrow Tol-DCs
      (i.v.), in combination with an immune-suppressor, a co-stimulator, and accessory
      cells can significantly extend renal allograft survival.

PMID- 24325420
TI  - Effectiveness of health education programs on exercise behavior among patients
      with heart disease: a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Regular exercise has been shown to be beneficial to
      patients with heart disease. Previous studies have indicated that health
      education can effectively increase participants' physical activity. However, no
      systematic review was conducted to evaluate the effectiveness of health education
      programs on changing exercise behavior among patients with heart disease. The aim
      of this study was to examine the effectiveness of health education programs on
      exercise behavior among heart disease patients. METHOD: Potential studies were
      retrieved in the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL,
      EMbase, PsycINFO, the British Nursing Index and Archive, Science Direct, and ERIC
      via EBSCOhost. Meta-analysis was done using the random-effect model. RESULTS:
      Thirty-seven studies were identified. Only 12 studies delivered health education
      based on various theories/models. Twenty-eight studies were included in the meta
      analyses. The results showed that health education had significantly positive
      effects on exercise adherence (risk ratio = 1.35 to 1.48), exercise duration (SMD
      = 0.25 to 0.69), exercise frequency (MD = 0.54 to 1.46 session/week), and
      exercise level (SMD = 0.25), while no significant effects were found on exercise
      energy expenditure and cognitive exercise behavior. CONCLUSION: Health education
      has overall positive effects on changing exercise behavior among heart disease
      patients. Few theoretical underpinning studies were conducted for changing
      exercise behavior among heart disease patients. The findings suggest that health
      education improves exercise behavior for heart disease patients. Health
      professionals should reinforce health education programs for them.

PMID- 24325421
TI  - Evidence-based healthcare and the Cochrane Collaboration: an unfinished journey
      as yet!
AB  - OBJECTIVE: Although evidence-based medicine and the Cochrane Collaboration have
      become key players in modern medicine, it is important to note that evidencebased
      medicine and the Cochrane Collaboration are confronted with a number of
      substantial challenges that need to be addressed. The aim of this work is to
      highlight some of these problems. METHODS: This comment is based on a semi
      structured literature review and my personal experience in the field of evidence
      based medicine. RESULTS: In this comment, 3 important areas of controversy and
      conflict ("Improving the quality of Cochrane Review"; "Increasing the relevance
      to middle- and low-income countries"; and "Keeping reviews up to date") will be
      highlighted, and possible solutions will be presented. CONCLUSION: With the
      Cochrane Collaboration now having been at the forefront of promoting and
      implementing core principles of evidence-based medicine, further organizational,
      political and administrative efforts will have to be put in place to further
      improve the impact of evidence-based medicine in the field of health care. This
      process can best be realized through networking and cooperation of the medical
      community worldwide, irrespective of geographic origin. When successfully
      tackling the above mentioned issues and obstacles, the already amazing success
      story of evidence-based medicine and the Cochrane Collaboration will grow even
      more substantial.

PMID- 24325426
TI  - Education section - the Cochrane Collaboration.

PMID- 24325427
TI  - Graft of a tissue-engineered neural scaffold serves as a promising strategy to
      restore myelination after rat spinal cord transection.
AB  - Remyelination remains a challenging issue in spinal cord injury (SCI). In the
      present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs)
      with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor
      tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS)
      scaffold. This was aimed to generate a tissue-engineered neural scaffold and to
      investigate whether it could enhance myelination after a complete T10 spinal cord
      transection in adult rats. Indeed, many NT-3 overexpressing SCs (NT-3-SCs) in the
      GS scaffold assumed the formation of myelin. More strikingly, a higher incidence
      of NSCs overexpressing TrkC differentiating toward myelinating cells was induced
      by NT-3-SCs. By transmission electron microscopy, the myelin sheath showed
      distinct multilayered lamellae formed by the seeded cells. Eighth week after the
      scaffold was transplanted, some myelin basic protein (MBP)-positive processes
      were observed within the transplantation area. Remarkably, certain segments of
      myelin derived from NSC-derived myelinating cells and NT-3-SCs were found to
      ensheath axons. In conclusion, we show here that transplantation of the GS
      scaffold promotes exogenous NSC-derived myelinating cells and SCs to form myelins
      in the injury/transplantation area of spinal cord. These findings thus provide a
      neurohistological basis for the future application or transplantation using GS
      neural scaffold to repair SCI. 

PMID- 24325428
TI  - The pro-fibrotic effects of pregnancy in a carbon-tetrachloride-induced liver
      injury in mouse model.
AB  - BACKGROUND & AIMS: Immune cells interact with hepatic-stellate-cells (HSCs) in
      the development of liver fibrosis. Little is known about the influence of
      pregnancy on the development and progression of hepatic-fibrosis. In this study,
      we explored the influence of pregnancy on progression of hepatic fibrosis.
      METHODS: Female mice (C57Blc) were induced by 4 injections of peritoneal carbon
      tetrachloride (CCl4) within 10 days, starting at day 10 of documented pregnancy.
      At end of experiment, serum samples were obtained for ALT and estradiol
      determination. Harvested livers were histological evaluated for liver injury and
      for protein alphaSMA expressions. Isolated intra-hepatic lymphocytes were
      assessed by flow cytometry. Isolated lymphocytes and serum samples were in- vitro
      co-cultured for 48 h with primary isolated naive HSCs. Washed cells were analyzed
      for adherence (anti-alphaSMA+/anti-CD45 + ) and proliferations (CSFE). RESULTS:
      CCl4-model for liver injury was well tolerated when induced in pregnancy similar
      to non-pregnant state. Hepatic-fibrosis (Masson Trichrome Stain, Sirius red stain
      and alphaSMA expressions) and necro-inflammation (H&E stain and serum ALT levels)
      significantly increased in pregnancy. Increased liver injury was accompanied with
      pro-fibrotic lymphocyte profile; CD8 subsets increased and NK cells decreased.
      HSCs activation significantly increased when in-vitro cultured with lymphocytes
      from pregnant as compared to non-pregnant fibrotic ones. Pro-fibrotic profile was
      also explained by decreased NK activity (CD107a marker) and of their
      phagocytosis. Serum estradiol levels although elevated in fibrosis conditions of
      pregnancy was not associated with the pHSCs activations. CONCLUSION: Liver
      fibrosis in our murine model was severe in pregnant model; via pro-fibrotic
      lymphocyte and serum alterations.

PMID- 24325429
TI  - Impact of forced vital capacity loss on survival after the onset of chronic lung
      allograft dysfunction.
AB  - RATIONALE: Emerging evidence suggests a restrictive phenotype of chronic lung
      allograft dysfunction (CLAD) exists; however, the optimal approach to its
      diagnosis and clinical significance is uncertain. OBJECTIVES: To evaluate the
      hypothesis that spirometric indices more suggestive of a restrictive ventilatory
      defect, such as loss of FVC, identify patients with distinct clinical,
      radiographic, and pathologic features, including worse survival. METHODS:
      Retrospective, single-center analysis of 566 consecutive first bilateral lung
      recipients transplanted over a 12-year period. A total of 216 patients developed
      CLAD during follow-up. CLAD was categorized at its onset into discrete
      physiologic groups based on spirometric criteria. Imaging and histologic studies
      were reviewed when available. Survival after CLAD diagnosis was assessed using
      Kaplan-Meier and Cox proportional hazards models. MEASUREMENTS AND MAIN RESULTS:
      Among patients with CLAD, 30% demonstrated an FVC decrement at its onset. These
      patients were more likely to be female, have radiographic alveolar or
      interstitial changes, and histologic findings of interstitial fibrosis. Patients
      with FVC decline at CLAD onset had significantly worse survival after CLAD when
      compared with those with preserved FVC (P < 0.0001; 3-yr survival estimates 9%
      vs. 48%, respectively). The deleterious impact of CLAD accompanied by FVC loss on
      post-CLAD survival persisted in a multivariable model including baseline
      demographic and clinical factors (P < 0.0001; adjusted hazard ratio, 2.73; 95%
      confidence interval, 1.86-4.04). CONCLUSIONS: At CLAD onset, a subset of patients
      demonstrating physiology more suggestive of restriction experience worse clinical
      outcomes. Further study of the biologic mechanisms underlying CLAD phenotypes is
      critical to improving long-term survival after lung transplantation.

PMID- 24325431
TI  - The impact factor: a useful indicator of journal quality or fatally flawed?

PMID- 24325432
TI  - Why don't younger adults in England go to have their eyes examined?
AB  - PURPOSE: Most research on attitudes to eye health has focussed on older people,
      reflecting the higher prevalence of eye diseases in older age groups. Little is
      known about younger people's attitudes to eye health. This paper explores young
      adults understanding of eye health and the purpose of eye examinations and the
      reasons why they do or do not attend for eye examinations. The aim is to provide
      evidence to inform policy on recommendations relating to eye health for
      individuals at low risk of visual impairment. METHODS: Six focus-group meetings
      were held in Leeds with 43 people aged 18-35 (mean age 22 years). Focus group
      participants were recruited using a snowballing approach from an initial group of
      young adults. Focus groups were transcribed and a thematic analysis approach was
      used. RESULTS: Children who wore spectacles were often bullied. As people grew up
      it became more socially acceptable to wear spectacles. Practicalities, aesthetics
      and fashion were important issues. Knowledge about eye disease and the eye
      examination were generally poor. Many claimed to value vision, but recognised
      that young people do not have eye examinations as often as they should. Eye
      examinations were only perceived to be needed for younger people experiencing
      problems or to update prescriptions. Eye health was seen as issue for older
      people. Some had no idea or were shocked about how much spectacles cost.
      Optometrists were seen differently to other healthcare professionals. The retail
      aspect of optometry was seen as too dominant. More information was wanted from
      the NHS on eye health. CONCLUSION: While young adults are at low risk of sight
      threatening disease, many do benefit from correction of refractive error. There
      is an argument for reducing the recommended frequency of eye examinations for low
      risk individuals from the 2 years currently advised. Nevertheless, young adults
      need to be made more aware of eye health issues, so that optometrists are seen as
      more than somewhere that sell spectacles. Increasing awareness of eye health in
      younger adulthood will also be important to ensure that services are
      appropriately accessed as they get older.

PMID- 24325433
TI  - Why don't older adults in England go to have their eyes examined?
AB  - PURPOSE: Preventable sight loss is one of the Public Health Outcome Indicators in
      England. Despite availability of NHS-funded eye examinations, many people do not
      take up their entitlement. This paper explores older adults understanding of eye
      health and the purpose of eye examinations and the reasons why they do or do not
      attend for eye examinations. The aim is to provide evidence to inform policy on
      increasing uptake of eye examinations among older people who have increased risk
      of preventable sight loss. METHODS: 10 focus-group meetings were held with people
      living in deprived areas of Leeds, recruited via community groups and
      neighbourhood networks. Focus groups were transcribed and a thematic analysis
      approach was used. RESULTS: The majority of participants were aged over 60, wore
      spectacles, and had regular eye examinations. Most were eligible for a NHS-funded
      eye examination. There was poor knowledge about eye disease and the purpose of
      different elements of the eye examination. Participants felt very vulnerable
      about getting the tests 'wrong' and looking foolish. Wearing of spectacles was
      associated with appearing old and frail. Many did not trust the veracity of
      optometrists, and perceived opticians to be expensive places, where it was
      difficult to control spending. Many had experienced 'hard sell' and opaque
      pricing. Most, but not all, were happy with the optometric services received.
      Participants indicated a preference for utilising a local optometrist located
      alongside other familiar health care services. CONCLUSION: Not-for-profit
      services co-located with other public services are needed to address concerns
      about cost of spectacles, lack of trust in optometrists, and poor access to eye
      examinations in local settings. It will also be important to raise public
      understanding about the purpose of eye examinations in terms of other causes of
      preventable sight loss and not just refractive error and need for spectacles.

PMID- 24325434
TI  - Social media use by patients with glaucoma: what can we learn?
AB  - PURPOSE: Much health-related information is available on the internet but its
      quality is known to be variable. This research aimed to analyse the ophthalmic
      content of social media platforms which has yet to be formally assessed. METHODS:
      Five online social media platforms were selected, the International Glaucoma
      Association (IGA) forum, Facebook, Twitter, YouTube and Patient Opinion.org.uk. A
      total of 3785 items were scraped from the sites, collated and analysed using
      simple thematic analysis by two coders. RESULTS: Fourteen themes were identified.
      The most commonly discussed topics included treatments, care experiences,
      promotions and support. Un-moderated sites contain more misleading information.
      Complementary therapies and treatments with a poor evidence base are presented
      more positively than established, evidence-based treatments. CONCLUSION: Online
      forums give patients a space to air questions, grievances, suggestions and to
      provide mutual support. The information they contain may be of use to physicians
      by flagging adverse drug reactions, areas for service improvement or topics about
      which patients require more information. There is a risk of exposure to
      misleading content which is heightened in un-moderated sites. Social media
      platforms may be an adjunct to current care models by providing a supportive and
      educational online community if these risks are understood.

PMID- 24325435
TI  - Evaluation of a global algorithm for wavefront reconstruction for Shack-Hartmann
      wave-front sensors and thick fundus reflectors.
AB  - PURPOSE: Conventional aberration analysis by a Shack-Hartmann aberrometer is
      based on the implicit assumption that an injected probe beam reflects from a
      single fundus layer. In fact, the biological fundus is a thick reflector and
      therefore conventional analysis may produce errors of unknown magnitude. We
      developed a novel computational method to investigate this potential failure of
      conventional analysis. METHODS: The Shack-Hartmann wavefront sensor was simulated
      by computer software and used to recover by two methods the known wavefront
      aberrations expected from a population of normally-aberrated human eyes and bi
      layer fundus reflection. The conventional method determines the centroid of each
      spot in the SH data image, from which wavefront slopes are computed for least
      squares fitting with derivatives of Zernike polynomials. The novel 'global'
      method iteratively adjusted the aberration coefficients derived from conventional
      centroid analysis until the SH image, when treated as a unitary picture,
      optimally matched the original data image. RESULTS: Both methods recovered higher
      order aberrations accurately and precisely, but only the global algorithm
      correctly recovered the defocus coefficients associated with each layer of fundus
      reflection. The global algorithm accurately recovered Zernike coefficients for
      mean defocus and bi-layer separation with maximum error <0.1%. The global
      algorithm was robust for bi-layer separation up to 2 dioptres for a typical SH
      wavefront sensor design. For 100 randomly generated test wavefronts with 0.7 D
      axial separation, the retrieved mean axial separation was 0.70 D with standard
      deviations (S.D.) of 0.002 D. CONCLUSIONS: Sufficient information is contained in
      SH data images to measure the dioptric thickness of dual-layer fundus reflection.
      The global algorithm is superior since it successfully recovered the focus value
      associated with both fundus layers even when their separation was too small to
      produce clearly separated spots, while the conventional analysis misrepresents
      the defocus component of the wavefront aberration as the mean defocus for the two
      reflectors. Our novel global algorithm is a promising method for SH data image
      analysis in clinical and visual optics research for human and animal eyes.

PMID- 24325436
TI  - The effect of caffeine on spontaneous pupillary oscillations.
AB  - PURPOSE: Caffeine stimulates the central nervous system, but the duration and
      extent of its influence on the pupil are not known. The aim of this study was to
      determine whether caffeine could have an effect on pupillary sleepiness waves,
      measured with the Pupillographic Sleepiness Test (PST) during routine clinical
      PST testing, where the caffeine dose-response of a participant cannot be
      registered before recording. METHODS: Twenty participants (aged between 22 and 51
      years, (mean 30.9 years +/- 8.9 SD, 11 women and nine men),.were tested at seven
      different time-points over 4.5 h. Each participant was tested under four
      conditions with coffee drunk or not between 1 and 2 h before the first
      measurement and/or 15 min afterwards. RESULTS: Caffeine caused a reduction in the
      Pupillary Unrest Index (PUI) with a maximal effect 1.25 h after consumption. A
      prolonged effect is found if coffee was consumed between 1 and 2 h before the
      first measurement. More excessive coffee consumers show prolongation of the
      effect. Subjective scales of sleepiness, alertness and craving for caffeine were
      significantly correlated to linear logarithm of PUI (lnPUI). CONCLUSIONS: We
      conclude that caffeine causes a dampening of the pupillary oscillations in well
      rested participants. As caffeine consumption can affect the PST for up to 6.5 h
      after intake, it is recommended that if PST measurements are to be carried out in
      the morning, caffeine consumption should not be allowed after midnight.

PMID- 24325437
TI  - Influence of eye rotation on peripheral eye length measurement obtained with a
      partial coherence interferometry instrument.
AB  - PURPOSE: The eye rotation approach for measuring peripheral eye length leads to
      concern about whether the rotation influences results, such as through pressure
      exerted by eyelids or extra-ocular muscles. This study investigated whether this
      approach is valid. METHODS: Peripheral eye lengths were measured with a Lenstar
      LS 900 biometer for eye rotation and no-eye rotation conditions (head rotation
      for horizontal meridian and instrument rotation for vertical meridian).
      Measurements were made for 23 healthy young adults along the horizontal visual
      field (+/- 30 degrees ) and, for a subset of eight participants along the
      vertical visual field (+/- 25 degrees ). To investigate the influence of the
      duration of eye rotation, for six participants measurements were made at 0, 60,
      120, 180 and 210 s after eye rotation to +/- 30 degrees  along horizontal and
      vertical visual fields. RESULTS: Peripheral eye lengths were not significantly
      different for the conditions along the vertical meridian (F1,7 = 0.16, p = 0.71).
      The peripheral eye lengths for the conditions were significantly different along
      the horizontal meridian (F1,22 = 4.85, p = 0.04), although not at individual
      positions (p >= 0.10) and were not important. There were no apparent differences
      between the emmetropic and myopic groups. There was no significant change in eye
      length at any position after maintaining position for 210 s. CONCLUSION: Eye
      rotation and no-eye rotation conditions were similar for measuring peripheral eye
      lengths along horizontal and vertical visual field meridians at +/- 30 degrees 
      and +/- 25 degrees , respectively. Either condition can be used to estimate
      retinal shape from peripheral eye lengths.

PMID- 24325438
TI  - How representative is the 'Representative Value' of refraction provided by the
      Shin-Nippon NVision-K 5001 autorefractor?
AB  - PURPOSE: The aim of the study was to evaluate the level of agreement between the
      'Representative Value' (RV) of refraction obtained from the Shin-Nippon NVision-K
      5001 instrument with values calculated from individual measurement readings using
      standard algebraic methods. METHODS: Cycloplegic autorefraction readings for 101
      myopic children aged 8-13 years (10.9 +/- 1.42 years) were obtained using the
      Shin-Nippon NVision-K 5001. Ten autorefractor measurements were taken for each
      eye. The spherical equivalent (SE), sphere (Sph) and cylindrical component (Cyl)
      power of each eye were calculated, firstly, by averaging the 10 repeated
      measurements (Mean SE, Mean Sph and Mean Cyl), and secondly, by the vector
      representation method (Vector SE, Vector Sph and Vector Cyl). These calculated
      values were then compared with those of RV (RV SE, RV Sph and RV Cyl) provided by
      the proprietary software of the NVision-K 5001 using one-way analysis of variance
      (anova). The agreement between the methods was also assessed. RESULTS: The SE of
      the subjects ranged from -5.37 to -0.62 D (mean +/- SD, = -2.89 +/- 1.01 D). The
      Mean SE was in exact agreement with the Vector SE. There were no significant
      differences between the RV readings and those calculated using non-vectorial or
      vectorial methods for any of the refractive powers (SE, p = 0.99; Sph, p = 0.93;
      Cyl, p = 0.24). The (mean +/- SD) differences were: RV SE vs Mean SE (and also RV
      SE vs Vector SE) -0.01 +/- 0.06 D; RV Sph vs Mean Sph, -0.01 +/- 0.05 D; RV Sph
      vs Vector Sph, -0.04 +/- 0.06 D; RV Cyl vs Mean Cyl, 0.01 +/- 0.07 D; RV Cyl vs
      Vector Cyl, 0.06 +/- 0.09 D. Ninety-eight percent of RV reading differed from
      their non-vectorial or vectorial counterparts by less than 0.25 D. CONCLUSION:
      The RV values showed good agreement to the results calculated using conventional
      methods. Although the formula used to calculate RV by the NVision-K 5001
      autorefractor is proprietary, our results provide validation for the use of RV
      measurements in clinical practice and vision science research.

PMID- 24325439
TI  - Prevalence of choroidal naevi using scanning laser ophthalmoscope.
AB  - PURPOSE: To determine the prevalence of choroidal naevi in a healthy population
      using an ultra-wide scanning laser ophthalmoscope which can capture up to a 200
      degrees  field of view of the retina, without pupil dilation. METHODS: Subjects
      were recruited from a college population. Each subject underwent an eye
      examination that included retinal and choroidal imaging using the Optos scanning
      laser ophthalmoscope and completed a self-administered questionnaire. Univariate
      and multivariate regression analysis were performed to identify associated
      factors with choroidal naevi. RESULTS: The Optomap images of 406 participants
      (mean age 23.5 +/- 4.4) were analysed. Thirty-nine subjects (10%) presented with
      at least one naevus in one eye, and multiple naevi were observed unilaterally in
      eight subjects. Drusen were noted in only one eye. The mean naevus diameter was
      2.38 mm (+/- 2.07). Prevalence was not associated with either eye colour, time
      spent outdoors, visual impairment, or ethnic group, but was significantly
      associated with male gender (OR 2.41, p = 0.009), blond/red hair colour (OR 2.42,
      p = 0.037), skin that neither burns nor tans (OR 2.8, p = 0.02) and habitual
      sunglasses use (OR 0.33, p = 0.002). CONCLUSIONS: A higher prevalence of
      choroidal naevi was detected in this college population compared to other
      population-based studies. This is likely due to the use of an ultra-wide field
      scanning laser ophthalmoscope which provides up to 200 degrees  of the fundus.
      The naevi were associated with several factors.

PMID- 24325440
TI  - Statutory requirements for visual fields and IOP measurement during an NHS eye
      examination in Scotland.

PMID- 24325441
TI  - Statutory requirements for visual fields and IOP measurement during an NHS eye
      examination in Scotland.

PMID- 24325443
TI  - The association between foodborne and orofecal pathogens and allergic
      sensitisation -- EuroPrevall study.
AB  - BACKGROUND: An inverse association between markers of exposure to foodborne and
      orofecal pathogens and allergic sensitization has been reported. However, the
      findings of epidemiological studies have not been consistent. This study
      investigated the relationship between antibodies to hepatitis A, Toxoplasma
      gondii and salmonella and allergic sensitization to food and aeroallergens in
      children from different geographical areas. METHODS: Specific IgE and/or skin
      prick testing against food and aeroallergens were measured in children from 6 to
      12 years of age residing in Greece, the Netherlands, China, India and Russia.
      Seropositivity to the three pathogens was measured, and data on potential
      confounders were collected using questionnaire. RESULTS: Data from 800 children
      (126 from Athens; 248 from Utrecht; 110 from Hong Kong; 119 from urban Tomsk; and
      197 from rural Tomsk) could be analysed. The highest percentage of positive
      serology to salmonella was found in Hong Kong (46.4%), to T. gondii in urban
      Tomsk (13.4%) and to hepatitis A in Athens (71.2%). Although not significant, T.
      gondii seropositivity tends to be negatively associated, and hepatitis A
      seropositivity tends to be positively associated with allergic sensitization.
      CONCLUSION: Inconsistent associations were observed between allergic
      sensitization to food and aeroallergens and markers of exposure to two common
      foodborne pathogens. The association with T. gondii tends to be negative,
      consistent with the 'hygiene hypothesis', but the association with hepatitis A
      tends to be positive. Taken together, there is no clear evidence that past
      exposure to foodborne and orofecal pathogens protects against allergic
      sensitization to food or aeroallergens.

PMID- 24325444
TI  - Is salamander hindlimb regeneration similar to that of the forelimb? Anatomical
      and morphogenetic analysis of hindlimb muscle regeneration in GFP-transgenic
      axolotls as a basis for regenerative and developmental studies.
AB  - The axolotl Ambystoma mexicanum is one of the most used model organisms in
      developmental and regenerative studies because it is commonly said that it can
      reconstitute a normal and fully functional forelimb/hindlimb after amputation.
      However, there is not a publication that has described in detail the regeneration
      of the axolotl hindlimb muscles. Here we describe and illustrate, for the first
      time, the regeneration of the thigh, leg and foot muscles in transgenic axolotls
      that express green fluorescent protein in muscle fibers and compare our results
      with data obtained by us and by other authors about axolotl forelimb regeneration
      and about fore- and hindlimb ontogeny in axolotls, frogs and other tetrapods. Our
      observations and comparisons point out that: (1) there are no muscle anomalies in
      any regenerated axolotl hindlimbs, in clear contrast to our previous study of
      axolotl forelimb regeneration, where we found muscle anomalies in 43% of the
      regenerated forelimbs; (2) during axolotl hindlimb regeneration there is a
      proximo-distal and a tibio-fibular morphogenetic gradient in the order of muscle
      regeneration and differentiation, but not a ventro-dorsal gradient, whereas our
      previous studies showed that in axolotl forelimb muscle regeneration there are
      proximo-distal, radio-ulnar and ventro-dorsal morphogenetic gradients. We discuss
      the broader implications of these observations for regenerative, evolutionary,
      developmental and morphogenetic studies. 

PMID- 24325445
TI  - The role of disgust in patients with hypochondriasis.
AB  - Theoretically, disgust sensitivity and disgust proneness could play an important
      role in hypochondriasis, since disgust is a defensive emotion widely believed to
      protect the organism from illness. However, empirical evidence to support this
      hypothesis has so far been based only on nonclinical samples, so that the
      importance and specificity of disgust for hypochondriasis remains unclear. In the
      current study, 36 patients with hypochondriasis, 27 with an anxiety disorder, and
      29 healthy controls completed several measures which included the assessment of
      disgust sensitivity (Scale for the Assessment of Disgust Sensitivity) and disgust
      proneness (Questionnaire for the Assessment of Disgust Proneness). We found that
      patients with hypochondriasis and those with an anxiety disorder had higher
      scores than those of the healthy controls for several measures of disgust
      proneness. Moreover, measures of hypochondriacal characteristics were associated
      with those of disgust proneness and disgust sensitivity. However, no differences
      were found between patients with hypochondriasis and those with anxiety
      disorders, with respect to disgust proneness and disgust sensitivity. Therefore,
      it can be assumed that disgust proneness and disgust sensitivity seem to be less
      specific than previously suggested for the development and maintenance of
      hypochondriasis. 

PMID- 24325446
TI  - Aerobic condition increases carotenoid production associated with oxidative
      stress tolerance in Enterococcus gilvus.
AB  - Although it is known that a part of lactic acid bacteria can produce carotenoid,
      little is known about the regulation of carotenoid production. The objective of
      this study was to determine whether aerobic growth condition influences
      carotenoid production in carotenoid-producing Enterococcus gilvus. Enterococcus
      gilvus was grown under aerobic and anaerobic conditions. Its growth was slower
      under aerobic than under anaerobic conditions. The decrease in pH levels and
      production of lactic acid were also lower under aerobic than under anaerobic
      conditions. In contrast, the amount of carotenoid pigments produced by E. gilvus
      was significantly higher under aerobic than under anaerobic conditions. Further,
      real-time quantitative reverse transcription PCR revealed that the expression
      level of carotenoid biosynthesis genes crtN and crtM when E. gilvus was grown
      under aerobic conditions was 2.55-5.86-fold higher than when it was grown under
      anaerobic conditions. Moreover, after exposure to 16- and 32-mM H2O2, the
      survival rate of E. gilvus grown under aerobic conditions was 61.5- and 72.5-fold
      higher, respectively, than when it was grown under anaerobic conditions. Aerobic
      growth conditions significantly induced carotenoid production and the expression
      of carotenoid biosynthesis genes in E. gilvus, resulting in increased oxidative
      stress tolerance.

PMID- 24325448
TI  - Retraction of molecular characterization of binding of calcium and carbohydrates
      by an early activation antigen of lymphocytes CD69.

PMID- 24325447
TI  - Purification and characterization of an extracellular esterase with organic
      solvent tolerance from a halotolerant isolate, Salimicrobium sp. LY19.
AB  - BACKGROUND: Halotolerant bacteria are excellent sources for selecting novel
      enzymes. Being intrinsically stable and active under high salinities, enzymes
      from these prokaryotes have evolved to function optimally under extreme
      conditions, making them robust biocatalysts with potential applications in harsh
      industrial processes. RESULTS: A halotolerant strain LY19 showing lipolytic
      activity was isolated from saline soil of Yuncheng Salt Lake, China. It was
      identified as belonging to the genus of Salimicrobium by 16S rRNA gene sequence
      analysis. The extracellular enzyme was purified to homogeneity with molecular
      mass of 57 kDa by SDS-PAGE. Substrate specificity test revealed that the enzyme
      preferred short-chain p-nitrophenyl esters and exhibited maximum activity towards
      p-nitrophenyl butyrate (p-NPB), indicating an esterase activity. The esterase was
      highly active and stable over broad temperature (20 degrees C-70 degrees C), pH
      (7.0-10.0) and NaCl concentration (2.5%-25%) ranges, with an optimum at 50
      degrees C, pH 7.0 and 5% NaCl. Significant inhibition of the esterase was shown
      by ethylenediaminetetraacetic acid (EDTA), phenylmethylsulfonyl fluoride (PMSF)
      and phenylarsine oxide (PAO), which indicated that it was a metalloenzyme with
      serine and cysteine residues essential for enzyme activity. Moreover, the
      esterase displayed high activity and stability in the presence of hydrophobic
      organic solvents with log P(ow) >= 0.88 than in the absence of an organic solvent
      or in the presence of hydrophilic solvents. CONCLUSIONS: Results from the present
      study indicated the novel extracellular esterase from Salimicrobium sp. LY19
      exhibited thermostable, alkali-stable, halotolerant and organic solvent-tolerant
      properties. These features led us to conclude that the esterase may have
      considerable potential for industrial applications in organic synthesis
      reactions.

PMID- 24325449
TI  - A purine nucleoside phosphorylase in Solanum tuberosum L. (potato) with
      specificity for cytokinins contributes to the duration of tuber endodormancy.
AB  - StCKP1 (Solanum tuberosum cytokinin riboside phosphorylase) catalyses the
      interconversion of the N9-riboside form of the plant hormone CK (cytokinin), a
      subset of purines, with its most active free base form. StCKP1 prefers CK to
      unsubstituted aminopurines. The protein was discovered as a CK-binding activity
      in extracts of tuberizing potato stolon tips, from which it was isolated by
      affinity chromatography. The N-terminal amino acid sequence matched the
      translation product of a set of ESTs, enabling a complete mRNA sequence to be
      obtained by RACE-PCR. The predicted polypeptide includes a cleavable signal
      peptide and motifs for purine nucleoside phosphorylase activity. The expressed
      protein was assayed for purine nucleoside phosphorylase activity against CKs and
      adenine/adenosine. Isopentenyladenine, trans-zeatin, dihydrozeatin and adenine
      were converted into ribosides in the presence of ribose 1-phosphate. In the
      opposite direction, isopentenyladenosine, trans-zeatin riboside, dihydrozeatin
      riboside and adenosine were converted into their free bases in the presence of
      Pi. StCKP1 had no detectable ribohydrolase activity. Evidence is presented that
      StCKP1 is active in tubers as a negative regulator of CKs, prolonging
      endodormancy by a chill-reversible mechanism. 

PMID- 24325451
TI  - Changes of HBsAg and HBV DNA levels in Chinese chronic hepatitis B patients after
      5 years of entecavir treatment.
AB  - BACKGROUND AND AIM: Hepatitis B surface antigen (HBsAg) kinetics during long-term
      entecavir therapy has not been well investigated. METHODS: We described the
      cumulative serologic, virologic, and biochemical outcomes and the occurrence of
      signature entecavir mutations among 222 Chinese treatment-naive chronic hepatitis
      B (CHB) patients receiving entecavir for up to 5 years. RESULTS: The median rate
      of HBsAg reduction over 5 years was 0.125 log IU/mL/year. Patients with high
      baseline HBV DNA levels (>= 8 log copies/mL or >= 7.3 log IU/mL), when compared
      with those with baseline hepatitis B virus (HBV) DNA < 7.3 log IU/mL, had a
      significantly greater median rate of HBsAg reduction (0.178 and 0.102 log
      IU/mL/year, respectively, P < 0.001). The difference in HBsAg decline was most
      prominent in the first year (0.324 and 0.062 log IU/mL/year, respectively, P <
      0.001). Greater median rates of HBsAg reduction were also found in hepatitis B e
      antigen (HBeAg)-positive patients when compared with HBeAg-negative patients
      (0.144 and 0.098 log IU/mL/year, P = 0.015), and in patients with high baseline
      HBsAg levels (>= 3 log IU/mL), when compared with patients with low baseline
      HBsAg < 3 log IU/mL (0.131 and 0.045 log IU/mL/year, respectively, P = 0.001).
      The 5-year cumulative rate of HBV DNA undetectability (< 20 IU/mL) was 97.1%.
      There were two cases of entecavir resistance, resulting in a 5-year cumulative
      resistance rate of 1.2%. CONCLUSION: In contrast to the profound HBV DNA
      suppression, long-term entecavir treatment achieved only a slow decline in serum
      HBsAg. Although certain patient subgroups exhibit a more rapid HBsAg reduction,
      additional therapeutic agents are needed to increase the chance of HBsAg
      seroclearance in CHB.

PMID- 24325452
TI  - Is there a need to redefine the diagnostic criteria for common variable
      immunodeficiency?
AB  - Common variable immunodeficiency (CVID) is a heterogeneous group of disorders,
      characterized by decreased serum levels of immunoglobulins and abnormal antibody
      response to protein and/or polysaccharide antigens, leading to recurrent
      respiratory and gastrointestinal infections, autoimmunity and malignancies.
      Meanwhile, several monogenic defects with CVID-like phenotype have been
      identified during the last decade. There is a need to reach international
      consensus by modifying criteria for CVID, considering various areas of
      uncertainty in the field. 

PMID- 24325450
TI  - The roles of FOXM1 in pancreatic stem cells and carcinogenesis.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses among
      all cancers. Over the past several decades, investigators have made great
      advances in the research of PDAC pathogenesis. Importantly, identification of
      pancreatic cancer stem cells (PCSCs) in pancreatic cancer cases has increased our
      understanding of PDAC biology and therapy. PCSCs are responsible for pancreatic
      tumorigenesis and tumor progression via a number of mechanisms, including
      extensive proliferation, self-renewal, high tumorigenic ability, high propensity
      for invasiveness and metastasis, and resistance to conventional treatment.
      Furthermore, emerging evidence suggests that PCSCs are involved in the malignant
      transformation of pancreatic intraepithelial neoplasia. The molecular mechanisms
      that control PCSCs are related to alterations of various signaling pathways, for
      instance, Hedgehog, Notch, Wnt, B-cell-specific Moloney murine leukemia virus
      insertion site 1, phosphoinositide 3-kinase/AKT, and Nodal/Activin. Also, authors
      have reported that the proliferation-specific transcriptional factor Forkhead box
      protein M1 is involved in PCSC self-renewal and proliferation. In this review, we
      describe the current knowledge about the signaling pathways related to PCSCs and
      the early stages of PDAC development, highlighting the pivotal roles of Forkhead
      box protein M1 in PCSCs and their impacts on the development and progression of
      pancreatic intraepithelial neoplasia. 

PMID- 24325453
TI  - Eugenia jambolana pretreatment prevents isoproterenol-induced myocardial damage
      in rats: evidence from biochemical, molecular, and histopathological studies.
AB  - Preventive effects of hydroalcoholic extract of fruit pulp of Eugenia jambolana
      (HEEJ) on isoproterenol (ISP)-induced myocardial damage in rats were evaluated.
      Rats were pre-treated with HEEJ (100, 200, and 400 mg/kg) daily for 30 days. ISP
      (85 mg/kg bw) was administered on the 28th and 29th days at an interval of 24 h.
      Ischemic control group exhibited significant increases in oxidative stress
      parameters, markers of inflammation, cardiac damage markers, and apoptotic
      markers. Oral pre-treatment with HEEJ (100, 200, and 400 mg/kg bw) provided
      cardioprotective activity by decreasing levels of malondialdehyde, cardiac
      markers (serum glutamate oxaloacetate transaminase, creatine kinase-myocardial
      band, cardiac troponin I), and markers of inflammation (interleukin-6, C-reactive
      protein, and tumor necrosis factor alpha); and increased levels of superoxide
      dismutase and reduced glutathione. HEEJ (400 mg/kg bw) was found to exert
      significantly greater effects in comparison to HEEJ (100 and 200 mg/kg bw).
      Apoptotic marker Bcl-2 was increased, while Bax was decreased in pre-treated
      rats, which was further confirmed by terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling assay. The present study provides evidence that
      pre-treatment with HEEJ attenuates oxidative stress, apoptosis and improves
      cardiac architecture in ISP-induced rats and, hence, is cardioprotective.

PMID- 24325454
TI  - Quercetin suppresses MIP-1alpha-induced adipose inflammation by downregulating
      its receptors CCR1/CCR5 and inhibiting inflammatory signaling.
AB  - Obesity-induced inflammation is characterized by recruitment of adipose tissue
      macrophages that release inflammatory cytokines and chemokines. MIP-1alpha
      (macrophage inflammatory protein 1alpha)/CCL3, a CC chemokine, induces
      monocyte/macrophage infiltration and thus is implicated in obesity-induced
      adipose inflammation. Quercetin has been shown to modulate obesity-induced
      inflammation, but the mechanism of its action remains unclear. Here we
      demonstrate that quercetin decreases MIP-1alpha release from adipocytes and
      macrophages and from cocultured adipocytes/macrophages; it also opposes MIP
      1alpha-induced macrophage infiltration and activation. The inhibitory action of
      quercetin on the MIP-1alpha-induced inflammatory responses of macrophages is
      mediated by downregulation of CCR1/CCR5, and inhibition of activation of JNK, p38
      mitogen-activated-protein kinase (MAPK), and IKK as well as IkappaBalpha
      degradation. These findings suggest that quercetin may be a useful agent against
      obesity-induced adipose tissue inflammation.

PMID- 24325456
TI  - Immunoadjuvant efficacy of N-carboxymethyl chitosan for vaccination via dendritic
      cell activation.
AB  - To induce humoral- and cell-mediated immune responses in protein-based
      vaccinations, immunoadjuvants are needed. In this study, we investigated the
      immunoadjuvant effect of N-carboxymethyl chitosan (N-CMCh) on the vaccination
      system through dendritic cell activation. The results showed that N-CMCh
      nanoparticle enhanced the secretion of cytokines (interleukin [IL]-6, IL-12p70,
      and tumor necrosis factor-alpha) and antigen uptake in bone marrow-derived
      dendritic cells. This activated antigen-specific Th1 cell responses, including IL
      2 and interferon-gamma production and proliferation. In addition, N-CMCh delayed
      the dissemination of ovalbumin (OVA) from an injection site in female C57BL/6
      mice. As a result, in the subcutaneous vaccination, OVA-N-CMCh nanoparticles
      enhanced both humoral and cell-mediated vaccine responses.

PMID- 24325455
TI  - Genistein at maximal physiologic serum levels induces G0/G1 arrest in MCF-7 and
      HB4a cells, but not apoptosis.
AB  - Several studies have demonstrated that a balanced diet can contribute to better
      human health. For this reason, soy-based food and pure isoflavones (pills) are
      one of the most consumed. The association of this consumption and lower risks of
      chronic diseases and cancer is well established for the Asian population and has
      been attracting the attention of people worldwide, especially women at menopause
      who seek to alleviate the symptoms associated with the lack of estrogen. Despite
      positive epidemiological data, concerns still exist because of conflicting
      results found in scientific literature with relation to the role of isoflavones
      in breast and hormone-related cancers. The aim of our study was to investigate
      the cytotoxicity, induction of apoptosis, and changes in apoptosis-related genes
      of maximal physiological serum levels of the isoflavone genistein (Gen) in MCF-7
      tumoral cells and in HB4a non-tumoral cells. In addition, induction of cell cycle
      arrest was also investigated. Only supraphysiological levels of Gen (50 and 100
      MUM) were cytotoxic to these cell lines. Concentrations of 10 and 25 MUM did not
      induce apoptosis and significant changes in expression of the studied genes.
      Positive results were found only in cell cycle analysis: G0/G1 delay of MCF-7
      cells in both concentrations of Gen and at 25 MUM in HB4a cells. It is the first
      study investigating effects of Gen in the HB4a cell line. Thus, despite the lack
      of apoptosis induction (generally found with high concentrations), Gen at
      physiologically relevant serum levels still exerts chemopreventive effects
      through the modulation of cell cycle.

PMID- 24325457
TI  - The effects of alpha-lipoic acid on liver oxidative stress and free fatty acid
      composition in methionine-choline deficient diet-induced NAFLD.
AB  - Development of nonalcoholic fatty liver disease (NAFLD) occurs through initial
      steatosis and subsequent oxidative stress. The aim of this study was to examine
      the effects of alpha-lipoic acid (LA) on methionine-choline deficient (MCD) diet
      induced NAFLD in mice. Male C57BL/6 mice (n=21) were divided into three groups
      (n=7 per group): (1) control fed with standard chow, (2) MCD2 group--fed with MCD
      diet for 2 weeks, and (3) MCD2+LA group--2 weeks on MCD receiving LA i.p. 100
      mg/kg/day. After the treatment, liver samples were taken for pathohistology,
      oxidative stress parameters, antioxidative enzymes, and liver free fatty acid
      (FFA) composition. Mild microvesicular hepatic steatosis was found in MCD2 group,
      while it was reduced to single fat droplets evident in MCD2+LA group. Lipid
      peroxidation and nitrosative stress were increased by MCD diet, while LA
      administration induced a decrease in liver malondialdehyde and nitrates+nitrites
      level. Similary, LA improved liver antioxidative capacity by increasing total
      superoxide dismutase (tSOD), manganese SOD (MnSOD), and copper/zinc-SOD
      (Cu/ZnSOD) activity as well as glutathione (GSH) content. Liver FFA profile has
      shown a significant decrease in saturated acids, arachidonic, and docosahexaenoic
      acid (DHA), while LA treatment increased their proportions. It can be concluded
      that LA ameliorates lipid peroxidation and nitrosative stress in MCD diet-induced
      hepatic steatosis through an increase in SOD activity and GSH level. In addition,
      LA increases the proportion of palmitic, stearic, arachidonic, and DHA in the
      fatty liver. An increase in DHA may be a potential mechanism of anti-inflammatory
      and antioxidant effects of LA in MCD diet-induced NAFLD.

PMID- 24325458
TI  - Phytochemical attributes of four conventionally extracted medicinal plants and
      cytotoxic evaluation of their extracts on human laryngeal carcinoma (HEp2) cells.
AB  - The bioactive composition and cytotoxic and antioxidative/prooxidative effects of
      four medicinal plants: yarrow (Achillea millefolium L.), hawthorn (Crataegus
      oxyacantha L.), ground ivy (Glechoma hederacea L.), and olive (Olea europea L.)
      on human laryngeal carcinoma cell line (HEp2) were investigated. Water extracts
      of these plants obtained by infusion, maceration, and decoction were
      characterized for their polyphenol content and antioxidant capacity. Based on the
      extraction efficiency of polyphenols, the final extracts were obtained whose
      polyphenolic profile, polysaccharides, mineral content, and cytoprotective
      activities were determined. The overall highest content of polyphenols and
      antioxidant capacity was determined in hawthorn, followed by yarrow and ground
      ivy, and the lowest in olive leaves extract. Phytochemical screening revealed the
      presence of phenolic acids, as the most abundant bioactive compounds, followed by
      flavonoids, flavons, and flavonols. All examined medicinal plants reduced the
      cell viability and reactive oxygen species formation in a dose- and time
      dependent manner. Ground ivy and yarrow containing a high content of phenolic
      acids and polysaccharides were more efficient to decrease the cell survival when
      compared to olive leaf and hawthorn. Experiments confirmed the importance of
      polyphenolic composition rather than content of investigated plants and revealed
      a relationship between the polyphenolic and polysaccharide contents and
      antioxidant/prooxidant characters of medicinal plants.

PMID- 24325459
TI  - Effect of tomato industrial processing (different hybrids, paste, and pomace) on
      inhibition of platelet function in vitro, ex vivo, and in vivo.
AB  - Cardiovascular disease (CVD) is the leading cause of death worldwide. Healthy
      eating is among its safeguards, especially the daily intake of fruits and
      vegetables. In this context it has been shown that tomato (Solanum lycopersicum)
      presents antiplatelet activity. In the present study, we evaluated in vitro
      antiplatelet activity of fresh hybrid tomato process (nine hybrids: Apt 410, H
      9888, Bos 8066, Sun 6366, AB3, HMX 7883, H 9665, H 7709, and H 9997), paste and
      its by-product of industrial processes (pomace). We assessed antiplatelet
      activity ex vivo and bleeding time in rats that ingested 0.1 and 1.0 g/kg of
      pomace each day. In studies in vitro, no significant differences in antiplatelet
      activity was observed in fresh tomato hybrids. Furthermore, the agro-industrial
      process did not affect the antiplatelet activity of paste and pomace. Likewise,
      pomace intake of 1.0 g/kg per day prolonged bleeding time and reduced ex vivo
      platelet aggregation in rats. The data obtained indicate that tomato has one or
      more compounds that caused antiplatelet activity. Regular consumption of tomato
      and its industrial derivatives could be part of a CVD prevention regimen.

PMID- 24325460
TI  - Complex formation between malate dehydrogenase and isocitrate dehydrogenase from
      Bacillus subtilis is regulated by tricarboxylic acid cycle metabolites.
AB  - In Bacillus subtilis, recent in vivo studies revealed that particular enzymes of
      the tricarboxylic acid cycle form complexes that allow an efficient transfer of
      metabolites. Remarkably, a complex of the malate dehydrogenase (Mdh) (EC
      1.1.1.37) with isocitrate dehydrogenase (Icd) (EC 1.1.1.42) was identified,
      although both enzymes do not catalyze subsequent reactions. In the present study,
      the interactions between these enzymes were characterized in vitro by surface
      plasmon resonance in the absence and presence of their substrates and cofactors.
      These analyses revealed a weak but specific interaction between Mdh and Icd,
      which was specifically stimulated by a mixture of substrates and cofactors of
      Icd: isocitrate, NADP(+) and Mg(2+). Wild-type Icd converted these substrates too
      fast, preventing any valid quantitative analysis of the interaction with Mdh.
      Therefore, binding of the IcdS104P mutant to Mdh was quantified because the
      mutation reduced the enzymatic activity by 174-fold but did not affect the
      stimulatory effect of substrates and cofactors on Icd-Mdh complex formation. The
      analysis of the unstimulated Mdh-IcdS104P interaction revealed kinetic constants
      of k(a) = 2.0 +/- 0.2 * 10(2) m(-1) .s(-1) and k(d) = 1.0 +/- 0.1 * 10(-3) .s(-1)
      and a K(D) value of 5.0 +/- 0.1 MUm. Addition of isocitrate, NADP(+) and Mg(2+)
      stimulated the affinity of IcdS104P to Mdh by 33-fold (K(D) = 0.15 +/- 0.01 MUm,
      k(a) = 1.7 +/- 0.7 * 10(3) m(-1) .s(-1), k(d) = 2.6 +/- 0.6 * 10(-4) .s(-1)).
      Analyses of the enzymatic activities of wild-type Icd and Mdh showed that Icd
      activity doubles in the presence of Mdh, whereas Mdh activity was slightly
      reduced by Icd. In summary, these data indicate substrate control of complex
      formation in the tricarboxylic acid cycle metabolon assembly and maintenance of
      the alpha-ketoglutarate supply for amino acid anabolism in vivo.

PMID- 24325461
TI  - Epithelial mesenchymal transition status is associated with anti-cancer responses
      towards receptor tyrosine-kinase inhibition by dovitinib in human bladder cancer
      cells.
AB  - BACKGROUND: Dovitinib (TKI-258) is a receptor tyrosine kinase (RTK) inhibitor
      targeting fibroblast growth factor receptor (FGFR) and further related RTKs. TKI
      258 is under investigation as anticancer drug for the treatment of various
      cancers including bladder cancer with aberrant RTK signaling. Here, we analyzed
      the responses of ten human bladder cancer cell lines towards TKI-258 treatment in
      relation to the epithelial mesenchymal transition (EMT) status of the cells.
      METHODS: Expression of epithelial marker E-cadherin as well as mesenchymal
      markers N-cadherin and vimentin was determined by quantitative RT-PCR and Western
      blot in RNA and protein extracts from the cultured cell lines. The cell responses
      were analyzed upon addition of TKI-258 by viability/proliferation (XTT assay) and
      colony formation assay for measurement of cell contact independent growth.
      RESULTS: The investigated bladder cancer cell lines turned out to display quite
      different EMT patterns as indicated by the abundance of E-cadherin or N-cadherin
      and vimentin. Protein and mRNA levels of the respective components strongly
      correlated. Based on E-cadherin and N-cadherin mRNA levels that were expressed
      approximately mutual exclusively, an EMT-score was calculated for each cell line.
      A high EMT-score indicated mesenchymal-like cells and a low EMT-score epithelial
      like cells. Then, we determined the IC50 values for TKI-258 by dose response
      curves (0-12 MUM TKI-258) in XTT assays for each cell line. Also, we measured the
      clonogenic survival fraction after adding TKI-258 (1 MUM) by colony formation
      assay. We observed significant correlations between EMT-score and IC50 values (r
      = 0.637, p = 0.0474) and between EMT-score and clonogenic survival fraction (r =
      0.635, p = 0.0483) as analyzed by linear regression analyses. CONCLUSIONS: In
      sum, we demonstrated that the EMT status based on E-cadherin and N-cadherin mRNA
      levels may be useful to predict responses towards TKI-258 treatment in bladder
      cancer.

PMID- 24325462
TI  - The pharmacokinetics of glycopyrrolate in Standardbred horses.
AB  - The disposition of plasma glycopyrrolate (GLY) is characterized by a three
      compartment pharmacokinetic model after a 1-mg bolus intravenous dose to
      Standardbred horses. The median (range) plasma clearance (Clp), volume of
      distribution of the central compartment (V1 ), volume of distribution at steady
      state (Vss), and area under the plasma concentration-time curve (AUC0-inf ) were
      16.7 (13.6-21.7) mL/min/kg, 0.167 (0.103-0.215) L/kg, 3.69 (0.640-38.73) L/kg,
      and 2.58 (2.28-2.88) ng*h/mL, respectively. Renal clearance of GLY was
      characterized by a median (range) of 2.65 (1.92-3.59) mL/min/kg and represented
      approximately 11.3-24.7% of the total plasma clearance. As a result of these
      studies, we conclude that the majority of GLY is cleared through hepatic
      mechanisms because of the limited extent of renal clearance of GLY and absence of
      plasma esterase activity on GLY metabolism. Although the disposition of GLY after
      intravenous administration to Standardbred horses was similar to that in
      Thoroughbred horses, differences in some pharmacokinetic parameter estimates were
      evident. Such differences could be attributed to breed differences or study
      conditions. The research could provide valuable data to support regulatory
      guidelines for GLY in Standardbred horses. 

PMID- 24325463
TI  - Prevalence, serovars and antimicrobial susceptibility of Salmonella spp. from
      wild and domestic green iguanas (Iguana iguana) in Grenada, West Indies.
AB  - Cloacal swabs from 62 green iguanas (Iguana iguana), including 47 wild and 15
      domestic ones from five parishes of Grenada, were sampled during a 4-month period
      of January to April 2013 and examined by enrichment and selective culture for the
      presence of Salmonella spp. Fifty-five per cent of the animals were positive, and
      eight serovars of Salmonella were isolated. The most common serovar was Rubislaw
      (58.8%), a serovar found recently in many cane toads in Grenada, followed by
      Oranienburg (14.7%), a serovar that has been causing serious human disease
      outbreaks in Japan. Serovar IV:48:g,z51 :- (formerly, S. Marina) highly invasive
      and known for serious infections in children in the United States, constituted
      11.8% of the isolates, all of them being from domestic green iguanas. Salmonella
      Newport, a serovar recently found in a blue land crab in Grenada, comprised 11.8%
      of the isolates from the green iguanas. The remaining four less frequent serovars
      included S. Javiana and S. Glostrup. Antimicrobial susceptibility tests conducted
      by a disc diffusion method against amoxicillin-clavulanic acid, ampicillin,
      cefotaxime, ceftazidime, ciprofloxacin, enrofloxacin, gentamicin, nalidixic acid,
      streptomycin, tetracycline and trimethoprim-sulfamethoxazole showed that drug
      resistance is minimal, with intermediate susceptibility, mainly to streptomycin,
      tetracycline and cefotaxime. This is the first report of isolation and
      antimicrobial susceptibilities of various Salmonella serovars from wild and
      domestic green iguanas in Grenada, West Indies. 

PMID- 24325464
TI  - Role of proton pump inhibitors in the occurrence of spontaneous bacterial
      peritonitis.

PMID- 24325465
TI  - Etiology, clinical outcome, and laboratory features in children with neutropenia:
      analysis of 104 cases.
AB  - BACKGROUND: Neutropenia is not uncommon in childhood. The aim of our study was to
      analyze the underlying causes of neutropenia and to evaluate its clinical
      significance in a series of children referred to our center. METHODS: One hundred
      and four consecutive children with neutropenia were enrolled in this study.
      Clinical and laboratory features were analyzed. RESULTS: The majority of patients
      (63.5%) showed chronic neutropenia. Among all chronic forms, the most frequent
      was chronic idiopathic neutropenia (CIN), followed by autoimmune neutropenia
      (AIN). Congenital neutropenia was identified in 6 patients. Acute neutropenia was
      mainly due to infections. Overall, at the time of first detection, neutropenia
      was more frequently severe or moderate. One-third of our patients who presented
      with severe neutropenia were ultimately diagnosed with a post-infectious acute
      form. Conversely, nearly half patients with CIN, AIN, or congenital neutropenia
      showed moderate/mild neutropenia at onset. Among patients with AIN and CIN,
      nearly half recovered between 7 months and 46 months and approximately one-fourth
      experienced infectious episodes during follow-up. No significant difference was
      noticed in terms of mean ANC between patients with and without remission, neither
      between patients with and without infections. CONCLUSIONS: Our study confirms the
      great etiological heterogeneity of neutropenia in children. We could not
      demonstrate a correlation between ANC level at onset and the underlying disorder,
      nor a correlation between mean ANC and duration of neutropenia or infectious
      episodes during follow-up. Neutropenia remains a disease of concern to
      pediatricians, requiring several laboratory investigations, prolonged follow-up,
      and, in few cases, advanced molecular methods.

PMID- 24325466
TI  - Allometry of left ventricular myocardial innervation.
AB  - Body mass (BM) of terrestrial mammalian species ranges from a few grams in the
      case of the Etruscan shrew to a few tonnes for an elephant. The mass-specific
      metabolic rate, as well as heart rate, decrease with increasing BM, whereas heart
      mass is proportional to BM. In the present study, we investigated the scaling
      behaviour of several compartments of the left ventricular myocardium, notably its
      innervation, capillaries and cardiomyocytes. Myocardial samples were taken from
      10 mammalian species with BM between approximately 2 g and 900 kg. Samples were
      analysed by design-based stereology and electron microscopy and the resulting
      data were subjected to linear regression and correlation analyses. The total
      length of nerve fibres (axons) in the left ventricle increased from 0.017 km
      (0.020 km) in the shrew to 7237 km (13,938 km) in the horse. The innervation
      density was similar among species but the mean number of axons per nerve fibre
      profile increased with rising BM. The total length of capillaries increased from
      0.119 km (shrew) to 10,897 km (horse). The volume of cardiomyocytes was 0.017
      cm(3) in the shrew and 1818 cm(3) in the horse. Scaling of the data against BM
      indicated a higher degree of complexity of the axon tree in larger animals and an
      allometric relationship between total length of nerve fibres/axons and BM. In
      contrast, the density of nerve fibres is independent of BM. It seems that the
      structural components of the autonomic nervous system in the heart are related to
      BM and heart mass rather than to functional parameters such as metabolic rate.

PMID- 24325467
TI  - Elevated levels of extracellular heat-shock protein 72 (eHSP72) are positively
      correlated with insulin resistance in vivo and cause pancreatic beta-cell
      dysfunction and death in vitro.
AB  - eHSP72 (extracellular heat-shock protein 72) is increased in the plasma of both
      types of diabetes and is positively correlated with inflammatory markers. Since
      aging is associated with a low-grade inflammation and IR (insulin resistance), we
      aimed to: (i) analyse the concentration of eHSP72 in elderly people and determine
      correlation with insulin resistance, and (ii) determine the effects of eHSP72 on
      beta-cell function and viability in human and rodent pancreatic beta-cells.
      Fasting blood samples were collected from 50 older people [27 females and 23
      males; 63.4+/-4.4 years of age; BMI (body mass index)=25.5+/-2.7 kg/m2]. Plasma
      samples were analysed for eHSP72, insulin, TNF (tumour necrosis factor)-alpha,
      leptin, adiponectin and cortisol, and glycaemic and lipid profile. In vitro
      studies were conducted using rodent islets and clonal rat and human pancreatic
      beta-cell lines (BRIN-BD11 and 1.1B4 respectively). Cells/islets were incubated
      for 24 h with eHSP72 (0, 0.2, 4, 8 and 40 ng/ml). Cell viability was measured
      using three different methods. The impact of HSP72 on beta-cell metabolic status
      was determined using Seahorse Bioscience XFe96 technology. To assess whether the
      effects of eHSP72 were mediated by Toll-like receptors (TLR2/TLR4), we co
      incubated rodent islets with eHSP72 and the TLR2/TLR4 inhibitor OxPAPC (oxidized
      1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine; 30 MUg/ml). We found a
      positive correlation between plasma eHSP72 and HOMA-IR (homoeostasis model
      assessment of IR) (r=0.528, P<0.001), TNF-alpha (r=0.389, P<0.014), cortisol
      (r=0.348, P<0.03) and leptin/adiponectin (r=0.334, P<0.03). In the in vitro
      studies, insulin secretion was decreased in an eHSP72 dose-dependent manner in
      BRIN-BD11 cells (from 257.7+/-33 to 84.1+/-10.2 MUg/mg of protein per 24 h with
      40 ng/ml eHSP72), and in islets in the presence of 40 ng/ml eHSP72 (from 0.48+/
      0.07 to 0.33+/-0.009 MUg/20 islets per 24 h). Similarly, eHSP72 reduced beta-cell
      viability (at least 30% for BRIN-BD11 and 10% for 1.1B4 cells). Bioenergetic
      studies revealed that eHSP72 altered pancreatic beta-cell metabolism. OxPAPC
      restored insulin secretion in islets incubated with 40 ng/ml eHSP72. In
      conclusion, we have demonstrated a positive correlation between eHSP72 and IR. In
      addition, we suggest that chronic eHSP72 exposure may mediate beta-cell failure. 

PMID- 24325468
TI  - Challenges of surveying wastewater drug loads of small populations and
      generalizable aspects on optimizing monitoring design.
AB  - AIMS: Quantifying illicit drug loads through wastewater analysis (WWA) is an
      alternative approach to estimating population drug use. This study investigated
      the variability of daily drug loads in wastewater and their relationships to
      environmental factors over an extended period to: (i) explore the suitability of
      WWA in small populations and (ii) optimize the monitoring design for future
      studies. DESIGN, SETTING, PARTICIPANTS: Daily wastewater samples (n = 1369
      consecutive days) from a German village with approximately 7160 inhabitants.
      MEASUREMENTS: Samples were analysed for cocaine and benzoylecgonine with liquid
      chromatography-tandem mass spectrometry. Time-series analysis was used to explore
      the effects of weather and other factors on daily cocaine loads. Subsampling was
      used to assess monitoring design. FINDINGS: Cocaine loads [mean = 652 mgCOC /day,
      standard deviation (SD) = 498 mgCOC /day] increased over the study period, with
      higher values during winter and spring. Despite high day-to-day variation, loads
      were significantly higher during weekends [+161 mgCOC /day, 95% confidence
      interval (CI) = 115-207 mgCOC /day, P < 10(-4) ] and days with frost (+114 mgCOC
      /day, 95% CI = 6-223 mgCOC /day, P = 0.039) or snow (+150 mgCOC /day, 95% CI = 46
      253 mgCOC /day, P = 0.005). Annual means estimated from 1-week periods were
      subject to approximately 60% relative error. Increasing sample size and changing
      sampling from consecutive days to stratified random decreased this uncertainty.
      CONCLUSIONS: Day-to-day variation and seasonality of drug loads from the few long
      term wastewater studies available to date suggest that up to 56 stratified random
      samples are required to obtain reliable (expected uncertainty around 10%) annual
      estimates of drug loads. Successfully assessing changes in consumption patterns
      or relationships to external factors requires larger sample sizes than estimating
      annual means, which holds true for high-prevalence drugs in small communities and
      low-prevalence drugs in big cities.

PMID- 24325469
TI  - Evaluation of a cholecystokinin 2 receptor-targeted near-infrared dye for
      fluorescence-guided surgery of cancer.
AB  - Surgical resection of malignant disease remains one of the most effective tools
      for treating cancer. Tumor-targeted near-infrared dyes have the potential to
      improve contrast between normal and malignant tissues, thereby enabling surgeons
      to more quantitatively resect malignant disease. Because the cholecystokinin 2
      receptor (CCK2R and its tumor-specific splice variant CCK2i4svR) is overexpressed
      in cancers of the lungs, colon, thyroid, pancreas, and stomach, but absent or
      inaccessible to parenterally administered drugs in most normal tissues, we have
      undertaken to design a targeting ligand that can deliver attached near-infrared
      dyes to CCK2R+ tumors. We report here the synthesis and biological
      characterization of a CCK2R-targeted conjugate of the near-infrared dye, LS-288
      (CRL-LS288). We demonstrate that CRL-LS288 binds selectively to CCK2R+ cancer
      cells with low nanomolar affinity (Kd = 7 * 10(-9) M). We further show that CRL
      LS288 localizes primarily to CCK2R-expressing HEK 293 murine tumor xenografts and
      that dye uptake in these xenografts is significantly reduced when CCK2R are
      blocked by preinjection of excess ligand (CRL) or when mice are implanted with
      CCK2R-negative tumors. Because CRL-LS288 is also found to reveal the locations of
      distant tumor metastases, we suggest that CRL-LS288 has the potential to
      facilitate intraoperative identification of malignant disease during a variety of
      cancer debulking surgeries. 

PMID- 24325470
TI  - Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation
      in celiac disease.
AB  - OBJECTIVE: The aim was to investigate the mucosal activation of a broad range of
      genes associated with the T-helper 17 cell (Th17) signaling pathway in children
      at different stages of celiac disease (CD), including children with increased
      risk for CD and children with untreated and gluten-free diet (GFD)-treated CD.
      MATERIAL AND METHODS: Small intestinal biopsies were taken from children with
      untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children
      with potential CD, and reference children. Real-time polymerase chain reaction
      (PCR) arrays were used to study the gene expression pattern of Th17-related
      genes, and quantitative PCR was used to study the interleukin (IL)-17A
      expression. RESULTS: The mucosal expression of CD8A was elevated at all stages of
      CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc,
      STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but
      had elevated levels of MMP3, IL-17, interferon-gamma (IFN-gamma) and CD8A,
      compared to references. The majority of the aforementioned genes, being
      differentially expressed in untreated CD, displayed similar expression in GFD
      treated children and references. Children with untreated and GFD-treated CD had
      elevated expression of IFN-gamma but had reduced expression of CD247.
      Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL
      17A levels. CONCLUSION: Mucosal upregulation of Th17 immunity occurs at the late
      stage of disease and is downregulated with dietary treatment, thus indicating
      that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is
      not fully downregulated by GFD.

PMID- 24325471
TI  - Significance of MDM2-309 polymorphisms and induced corresponding plasma MDM2
      levels in susceptibility to laryngeal squamous cell carcinoma.
AB  - The tumor suppressor p53 plays a crucial role in maintaining genomic stability
      and tumor prevention. Murine double-minute 2 (MDM2) oncoprotein plays a pivotal
      role in regulating p53, and the single-nucleotide polymorphism (SNP) 309T/G SNP
      in the promoter region of Mdm2 has been shown to be associated with increased
      risk of cancer. We investigated the association between Mdm2-309 promoter
      polymorphism, plasma MDM2 levels, and risk of laryngeal squamous cell carcinoma
      (LSCC). In this case-control study, 146 patients with LSCC, 61 patients with
      vocal leukoplakia, and 212 healthy controls were genotyped for the Mdm2-309 T/G
      gene using pyrosequencing. Plasma MDM2 levels were also analyzed by enzyme-linked
      immunosorbent assay (ELISA). Patients with LSCC had a significantly lower
      frequency of GT at Mdm2-309 (odds ratio [OR]=0.50, p=0.02) than controls. The
      proportion of GT heterozygotes in advanced stage cases were less than that in the
      initial stage patients (OR: 0.36 vs. 0.63; p=0.007 and 0.16). The same result was
      found between cases with and without lymph node metastases (OR: 0.45 vs. 0.52;
      p=0.075 and 0.04). Moreover, the plasma Mdm2 concentrations of LSCC patients
      (343.36+/-14.8 pg/mL) were significantly higher than those in controls (255.76+/
      8.2 pg/mL; p<0.01) and vocal leukoplakia patients (301.42+/-8.6 pg/mL; p<0.05).
      Patients in advanced stages and with lymph node metastasis had higher plasma MDM2
      levels, while the GT genotypes (308.06+/-18.9 pg/mL; p=0.037) had lower MDM2
      plasma levels than the TT genotypes (369.00+/-25.2 pg/mL). The Mdm2 SNP309 G
      allele is implicated as an important LSCC and a vocal leukoplakia protective
      factor in the Chinese Han Population, and the proportion of GT genotype was lower
      in advanced LSCC patients and lymph node metastasis patients. Moreover, Mdm2-309
      GT genotype patients had a lower plasma MDM2 level than the TT genotypes.

PMID- 24325473
TI  - What is your diagnosis? Lung impression smear from a stray kitten.

PMID- 24325472
TI  - Effects of the n-6/n-3 polyunsaturated fatty acids ratio on postprandial
      metabolism in hypertriacylglycerolemia patients.
AB  - BACKGROUND: Atherosclerosis is a postprandial phenomenon. The balanced n-6/n-3
      PUFA ratio contributing to the prevention of atherosclerosis has been well shown,
      but the effect of the ratio on postprandial metabolism has not been fully
      investigated. The aim of this study was to investigate the effects of the n-6/n-3
      PUFAs ratio on postprandial metabolism in hypertriacylglycerolemia patients,
      comparing them to healthy controls. METHODS: Test meals with 0.97 (high n-3) and
      8.80 (low n-3) n-6/n-3 PUFAs ratio were administered in a randomized crossover
      design to 8 healthy and 8 hypertriacylglycerolemia subjects. Blood samples were
      collected for 8 hours after meals to measure triglyceride (TG), total cholesterol
      (TC), HDL, ApoA, ApoB, glucose, insulin, inflammatory makers including tumor
      necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), endothelial function
      including nitric oxide (NO) and endothelin-1 (ET-1). RESULTS: According to
      repeated-measures ANOVA, the postprandial response of lipid, glucose, insulin,
      inflammation and endothelial function were not significantly different between
      meals. The postprandial TG and NO response were significantly different between
      healthy control (HC) and hypertriglyceridemia group (HTG) after both meals (P <
      0.01). After both meals maximal change and iAUC for TG was all higher in HTG
      group than HC group, the difference was significant after low n-3 meal but not
      after high n-3 meal. The concentration of glucose, insulin, IL-6, TNFalpha and ET
      1 at each time point was higher and NO was lower in HTG group, but the maximal
      change and iAUC had no significant difference except for iAUC of insulin, IL-6
      and diAUC of NO after low n-3 meal. CONCLUSIONS: The ratio of n-6 and n-3 maybe
      do not acutely influence the postprandial metabolism, inflammatory response and
      endothelial function, but the low n-3 meal can strengthen the difference between
      HTG and HC group.

PMID- 24325474
TI  - Optimization of antitumor modulators of pre-mRNA splicing.
AB  - The spliceosome regulates pre-mRNA splicing, which is a critical process in
      normal mammalian cells. Recently, recurrent mutations in numerous spliceosomal
      proteins have been associated with a number of cancers. Previously, natural
      product antitumor agents have been shown to interact with one of the proteins
      that is subject to recurrent mutations (SF3B1). We report the optimization of a
      class of tumor-selective spliceosome modulators that demonstrate significant in
      vivo antitumor activity. This optimization culminated in the discovery of
      sudemycin D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2
      (IC50 = 39 nM) and other tumor cell lines, including JeKo-1 (IC50 = 22 nM), HeLa
      (IC50 = 50 nM), and SK-N-AS (IC50 = 81 nM). We also report improved processes for
      the synthesis of these compounds. Our work supports the idea that sudemycin D6 is
      worthy of further investigation as a novel preclinical anticancer agent with
      application in the treatment of numerous human cancers. 

PMID- 24325476
TI  - Spontaneous, non-cirrhotic, intrahepatic porto-systemic shunt presenting as acute
      encephalopathy.

PMID- 24325475
TI  - Targeting interleukin-13 with tralokinumab attenuates lung fibrosis and
      epithelial damage in a humanized SCID idiopathic pulmonary fibrosis model.
AB  - The aberrant fibrotic and repair responses in the lung are major hallmarks of
      idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been
      used in the clinic with limited success, raising the possibility that an
      effective therapeutic strategy in this disease must inhibit fibrosis and promote
      appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF,
      but its disease association and mechanism of action remains unknown. In the
      present study, an overexpression of IL-13 and IL-13 pathway markers was
      associated with IPF, particularly a rapidly progressive form of this disease.
      Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using
      tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling
      in this model. However, targeting IL-13 was also found to promote lung repair and
      to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic
      processes and enhances repair processes in the lung.

PMID- 24325477
TI  - Comments on: "In vivo bone regeneration using tubular perfusion system bioreactor
      cultured nanofibrous scaffolds" vascularization--one challenge of tissue
      engineering.

PMID- 24325478
TI  - Workforce planning needs to improve.

PMID- 24325496
TI  - Long-term workforce solutions needed to reduce agency spend.

PMID- 24325502
TI  - Lower urinary tract infections.

PMID- 24325503
TI  - Working on my own terms.
AB  - Six months after being named nurse of the year in 2007, Justine Whitaker left the
      NHS in a blaze of publicity, citing her disillusionment with increasing red tape
      and a culture of fear. Now an independent nurse, lecturer and business owner, she
      says NHS reforms still directly affect her.

PMID- 24325504
TI  - Gentle persuasion works well.
AB  - Nurses often have difficulty discussing unhealthy behaviours with patients. These
      conversations can be made less awkward, and more effective, by using positive and
      empathetic techniques such as motivational interviewing. Nurses describe the
      approaches that they have found effective.

PMID- 24325505
TI  - Gold standard support.
AB  - Prostate Cancer UK has launched a checklist of 15 standards covering every stage
      of the patient journey, including diagnosis, to encourage consistent quality in
      services across the UK. Supported by nurse champions, the checklist tells
      patients what they should expect and gives clinicians standards they can aspire
      to.

PMID- 24325506
TI  - East meets West.
AB  - A delegation from RCN Publishing and the RCN visited Beijing in September, where
      they saw how the city's hospitals integrate traditional Chinese and western
      medicine. Nursing schools in China are expanding their student intake to meet
      government targets. At the same time, nursing representatives are forging links
      and exchanging ideas with their counterparts in other countries, including the
      UK.

PMID- 24325519
TI  - Patients would benefit from having two types of nurses.

PMID- 24325520
TI  - Care would have improved long ago if nurse's warnings had been heeded.

PMID- 24325521
TI  - The accountability of nurses and healthcare assistants.

PMID- 24325523
TI  - We need safe staffing in care homes as well as hospitals.

PMID- 24325524
TI  - The most vulnerable people in society deserve better from us.

PMID- 24325525
TI  - Please take the time to lobby your MP about the care bill.

PMID- 24325529
TI  - Obtaining and communicating information about genetics and genomics.
AB  - This is the eighth article in a series looking at how nurses can develop
      competence in genetics and genomics health care. The article explores the many
      ways in which nurses can acquire up to date and accurate genetic and genomic
      information, with the intention of improving their knowledge base. It enables
      nurses to discover the best ways of giving specific and complex information to
      patients and colleagues effectively and using straightforward language. 

PMID- 24325530
TI  - Effects of stroke on informal carers.
AB  - Informal carers have a pivotal role in caring for patients who have had a stroke.
      Research has shown that informal carers have unmet information, psychological and
      social needs. There is a lack of research about how informal carers in Northern
      Ireland manage the role of caring for a patient who has experienced stroke, and
      what kind of support they need and receive. This literature review explores the
      experiences of informal carers providing stroke care in the home. The issues
      highlighted in the article are relevant worldwide, because the incidence of
      stroke is increasing in developed and developing countries. 

PMID- 24325531
TI  - Management of acute confusion in patients with CNS infections.
AB  - This article discusses the management of acute confusion and aggression in
      patients with infections of the central nervous system (CNS). The issues
      discussed are applicable to the management of acute confusion of any cause and
      the principles of care apply to all confused patients. The article addresses many
      of the challenges encountered by nurses caring for confused patients, including
      the recognition of acute confusion, use of screening tools, and the management
      and treatment of these patients. 

PMID- 24325532
TI  - Compassionate care.

PMID- 24325533
TI  - Map of opportunity.

PMID- 24325534
TI  - Counselling the carers.

PMID- 24325536
TI  - Increasing understanding of neuromuscular disease.

PMID- 24325537
TI  - Student life - acting responsibly.

PMID- 24325538
TI  - Student life - be prepared.

PMID- 24325539
TI  - Prolonged exposure to loteprednol etabonate in human tear fluid and rabbit ocular
      tissues following topical ocular administration of Lotemax gel, 0.5%.
AB  - PURPOSE: A new gel formulation containing loteprednol etabonate (LE), a C-20
      ester corticosteroid used to treat ocular inflammation, was developed to provide
      increased retention on the ocular surface for improved drug delivery to
      intraocular tissues. This investigation evaluated concentrations of LE in tear
      fluid following topical instillation of LE gel to humans and the ocular and
      systemic pharmacokinetics of LE following administration to rabbits. METHODS: LE
      ophthalmic gel 0.5% was administered as a single topical dose to human volunteers
      (n=12) and Dutch Belted rabbits (n=40). In the human study, tear sampling was
      performed at 6, 9, 12, and 24 h after instillation. In the rabbit study, tears
      and ocular tissues were collected from 5 min through 24 h postdose. Serial blood
      samples were collected from one cohort of rabbits for plasma analysis.
      Concentrations of LE were determined by high performance liquid chromatography
      tandem mass spectrometry. RESULTS: In humans, LE was detected in tears at all the
      time points assessed with mean concentrations of 114 MUg/g at 6 h declining to
      2.41 MUg/g at 24 h postdose. In rabbits, LE was detected in all ocular tissues
      within 5 min after dosing. Maximum concentrations of LE were achieved within 0.5
      h and were highest in tear fluid (1560 MUg/g), followed by bulbar conjunctiva
      (4.03 MUg/g), cornea, (2.18 MUg/g), iris/ciliary body (0.162 MUg/g), and aqueous
      humor (0.0138 MUg/mL). LE remained measurable in all ocular tissues through 24 h
      with the exception of aqueous humor. In contrast, plasma levels of LE were low
      with no detectable levels after 4 h. CONCLUSIONS: The gel formulation of LE
      provided prolonged exposure to LE on the ocular surface, with measurable levels
      in tears through 24 h in both humans and rabbits, for delivery of LE to anterior
      segment tissues, as evidenced by sustained levels of LE in rabbit conjunctiva,
      cornea, and iris/ciliary body.

PMID- 24325540
TI  - Novel central nervous system drug delivery systems.
AB  - For decades, biomedical and pharmaceutical researchers have worked to devise new
      and more effective therapeutics to treat diseases affecting the central nervous
      system. The blood-brain barrier effectively protects the brain, but poses a
      profound challenge to drug delivery across this barrier. Many traditional drugs
      cannot cross the blood-brain barrier in appreciable concentrations, with less
      than 1% of most drugs reaching the central nervous system, leading to a lack of
      available treatments for many central nervous system diseases, such as stroke,
      neurodegenerative disorders, and brain tumors. Due to the ineffective nature of
      most treatments for central nervous system disorders, the development of novel
      drug delivery systems is an area of great interest and active research. Multiple
      novel strategies show promise for effective central nervous system drug delivery,
      giving potential for more effective and safer therapies in the future. This
      review outlines several novel drug delivery techniques, including intranasal drug
      delivery, nanoparticles, drug modifications, convection-enhanced infusion, and
      ultrasound-mediated drug delivery. It also assesses possible clinical
      applications, limitations, and examples of current clinical and preclinical
      research for each of these drug delivery approaches. Improved central nervous
      system drug delivery is extremely important and will allow for improved treatment
      of central nervous system diseases, causing improved therapies for those who are
      affected by central nervous system diseases. 

PMID- 24325541
TI  - Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin
      phosphate after a single oral and i.v. administration in chickens.
AB  - The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin
      phosphate were carried out in broiler chickens according to a principle of single
      dose, random, parallel design. The two formulations of tylosin were given orally
      and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight
      fasting (n = 10 chickens/group). Serial blood samples were collected at different
      time points up to 24 h postdrug administration. A high performance liquid
      chromatography method was used for the determination of tylosin concentrations in
      chicken plasma. The tylosin plasma concentration's time plot of each chicken was
      analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described
      by a one-compartmental open model 1st absorption after oral administration. After
      intravenous administration the pharmacokinetics of tylosin was best described by
      a two-compartmental open model, and there were no significant differences between
      tylosin tartrate and tylosin phosphate. After oral administration, there were
      significant differences in the Cmax (0.18 +/- 0.01, 0.44 +/- 0.09) and AUC (0.82
      +/- 0.05, 1.57 +/- 0.25)between tylosin phosphate and tylosin tartrate. The
      calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate
      were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that,
      the absorption of tylosin tartrate is better than tylosin phosphate after oral
      administration. 

PMID- 24325542
TI  - Endoscopic diagnosis of early neoplasia of the esophagus with narrow band
      imaging: correlations among background coloration and iodine staining findings.
AB  - BACKGROUND AND AIM: It was previously reported that high-grade intraepithelial
      neoplasia of the esophagus turns pink within a few minutes after iodine staining
      (pink-color sign; PCS); however, iodine staining is uncomfortable. By using
      narrow band imaging (NBI), color change in the area between the intraepithelial
      papillary capillary loop (background coloration; BGC) is often observed within
      the brownish area. The diagnostic usefulness of BGC findings for differentiating
      high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia was
      evaluated. METHODS: In a prospective observational study from September 2010 to
      August 2012, 285 patients who were in a high-risk group for esophageal squamous
      cell carcinoma underwent endoscopic examination. Lesions with both endoscopic
      findings of dilated intraepithelial papillary capillary loop on NBI and iodine
      unstained areas were studied, in which endoscopic biopsy or endoscopic resection
      was subsequently performed. The esophageal background mucosa was also evaluated
      on the basis of the iodine staining pattern (uniform type: Group U, scattered
      type: Group S). RESULTS: One hundred three esophageal lesions in 87 patients were
      studied. When BGC was used as the differentiation index, sensitivity was 93.8%,
      specificity was 88.2%, and accuracy was 91.3%. When PCS was used, sensitivity was
      97.9%, specificity was 88.2%, and accuracy was 93.2% (P = 0.79). In Group U (n =
      54), BGC had an accuracy of 93.8%, and PCS had an accuracy of 92.3% (P = 1.0). On
      the other hand, in Group S (n = 33), BGC had an accuracy of 86.8%, while PCS had
      an accuracy of 94.7% (P = 0.27). CONCLUSIONS: Diagnosis using BGC on NBI may
      substitute for diagnosis based on PCS in many patients.

PMID- 24325543
TI  - Collection of Oral Fluids Using Cotton Ropes as a Sampling Method to Detect Foot
      and-Mouth Disease Virus Infection in Pigs.
AB  - In high-density farming practices, it is important to constantly monitor for
      infectious diseases, especially diseases that have the potential to spread
      rapidly between holdings. Pigs are known to amplify foot-and-mouth disease (FMD)
      by excreting large amounts of virus, and it is therefore important to detect the
      virus quickly and accurately to minimize the spread of disease. Ropes were used
      to collect oral fluid samples from pigs, and each sample was compared to saliva
      samples collected from individual animals by detecting FMD virus RNA using real
      time PCR. Two different experiments are described where groups of pigs were
      infected with different serotypes of FMD virus, either with or without
      vaccination, and unvaccinated pigs were kept in aerosol contact. The sensitivity
      of the rope sampling varied between 0.67 and 0.92, and the statistical agreement
      between this method and individual sampling ranged from substantial to moderate
      for the two different serotypes. The ease of collecting oral fluids using ropes
      together with the high sensitivity of subsequent FMD detection through PCR
      indicates that this could be a useful method to monitor pig populations for FMD
      virus infection. With further validation of the sensitivity of detection of FMD
      virus RNA, this can be a cost-effective, non-invasive diagnostic tool.

PMID- 24325544
TI  - Erosive and cariogenicity potential of pediatric drugs: study of physicochemical
      parameters.
AB  - BACKGROUND: Pediatric medications may possess a high erosive potential to dental
      tissues due to the existence of acid components in their formulations. The
      purpose was to determine the erosive and cariogenic potential of pediatric oral
      liquid medications through the analysis of their physicochemical properties in
      vitro. METHODS: A total of 59 substances were selected from the drug reference
      list of the National Health Surveillance Agency (ANVISA), which belong to 11
      therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory,
      corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials,
      antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of
      pH was performed by potentiometry, using a digital pH meter. For the Total
      Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used,
      which was titrated until drug pH was neutralized. The Total Soluble Solids
      Contents (TSSC) quantification was carried out by refractometry using Brix scale
      and the analysis of Total Sugar Content was performed according to Fehling's
      method. In addition, it was analyzed the information contained in the drug
      inserts with regard to the presence of sucrose and type of acid and sweetener
      added to the formulations. RESULTS: All drug classes showed acidic pH, and the
      lowest mean was found for antipsychotics (2.61 +/- 0.08). There was a large
      variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total
      sugar contents were identified in the antitussives (53.25%) and anticonvulsants
      (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the
      formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and
      sorbitol (34.8%). CONCLUSION: The drugs analyzed herein showed physicochemical
      characteristics indicative of a cariogenic and erosive potential on dental
      tissues. Competent bodies' strategies should be implemented in order to broaden
      the knowledge of health professionals, drug manufacturers and general consuming
      public about the risks from the consumption of medicines potentially harmful to
      dental tissues.

PMID- 24325545
TI  - Predictive factors of overall quality of life in advanced cancer patients using
      EORTC QLQ-C30.
AB  - OBJECTIVE: To identify which domains/symptoms from the European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
      were predictive of overall quality of life (QoL) in advanced cancer patients.
      METHODS: Four hundred and forty seven patients with brain metastases or bone
      metastases from seven countries were enrolled with regression analysis to
      determine the predictive value of the QLQ-C30 functional/symptom scores for
      patient reported overall QoL (question 30), overall health (question 29) and the
      global health status domain (questions 29 and 30). RESULTS: Worse role
      functioning, social functioning, fatigue and financial problems were the most
      significant predictive factors for worse QoL. In the bone metastases subgroup (n
      = 400), role functioning, fatigue and financial problems were the most
      significant predictors. In patients with brain metastases (n = 47), none of the
      EORTC domains significantly predicted worse QOL. CONCLUSION: Deterioration of
      certain QLQ-C30 functional/symptom scores significantly contributes to worse QoL,
      overall health and global health status.

PMID- 24325546
TI  - Involvement of nitric oxide synthase in matrix metalloproteinase-9- and/or
      urokinase plasminogen activator receptor-mediated glioma cell migration.
AB  - BACKGROUND: Src tyrosine kinase activates inducible nitric oxide synthase (iNOS)
      and, in turn, nitric oxide production as a means to transduce cell migration. Src
      tyrosine kinase plays a key proximal role to control alpha9beta1 signaling. Our
      recent studies have clearly demonstrated the role of alpha9beta1 integrin in
      matrix metalloproteinase-9 (MMP-9) and/or urokinase plasminogen activator
      receptor (uPAR)-mediated glioma cell migration. In the present study, we
      evaluated the involvement of alpha9beta1 integrin-iNOS pathway in MMP-9- and/or
      uPAR-mediated glioma cell migration. METHODS: MMP-9 and uPAR shRNAs and
      overexpressing plasmids were used to downregulate and upregulate these molecules,
      respectively in U251 glioma cells and 5310 glioma xenograft cells. The effect of
      treatments on migration and invasion potential of these glioma cells were
      assessed by spheroid migration, wound healing, and Matrigel invasion assays. In
      order to attain the other objectives we also performed immunocytochemical,
      immunohistochemical, RT-PCR, Western blot and fluorescence-activated cell sorting
      (FACS) analysis. RESULTS: Immunohistochemical analysis revealed the prominent
      association of iNOS with glioblastoma multiforme (GBM). Immunofluorescence
      analysis showed prominent expression of iNOS in glioma cells. MMP-9 and/or uPAR
      knockdown by respective shRNAs reduced iNOS expression in these glioma cells. RT
      PCR analysis revealed elevated iNOS mRNA expression in either MMP-9 or uPAR
      overexpressed glioma cells. The migration potential of MMP-9- and/or uPAR
      overexpressed U251 glioma cells was significantly inhibited after treatment with
      L-NAME, an inhibitor of iNOS. Similarly, a significant inhibition of the invasion
      potential of the control or MMP-9/uPAR-overexpressed glioma cells was noticed
      after L-NAME treatment. A prominent reduction of iNOS expression was observed in
      the tumor regions of nude mice brains, which were injected with 5310 glioma
      cells, after MMP-9 and/or uPAR knockdown. Protein expressions of cSrc, phosphoSrc
      and p130Cas were reduced with simultaneous knockdown of both MMP-9 and uPAR.
      CONCLUSIONS: Taken together, our results from the present and earlier studies
      clearly demonstrate that alpha9beta1 integrin-mediated cell migration utilizes
      the iNOS pathway, and inhibition of the migratory potential of glioma cells by
      simultaneous knockdown of MMP-9 and uPAR could be attributed to the reduced
      alpha9beta1 integrin and iNOS levels.

PMID- 24325547
TI  - Resonance frequency analysis as a predictor of early implant failure in the
      partially edentulous posterior maxilla following immediate nonfunctional loading
      or delayed loading with single unit restorations.
AB  - OBJECTIVES: To assess the ability of baseline resonance frequency analysis (RFA)
      measurements to predict early implant failure in the posterior maxilla and to
      evaluate potential correlations between this measurement with Hounsfield units,
      bone quality variables, and implant dimension. MATERIALS AND METHODS: This
      prospective randomized study involved 46 SLActive Straumann implants placed in
      the posterior maxillae of 21 subjects. Each patient received at least one control
      (delayed loading) and one experimental (immediate nonfunctional loading) implant.
      Each site was evaluated with presurgical computer-assisted tomography (CT) scans,
      histomorphometric analysis of bone cores, and subjective determination of bone
      quality. Baseline implant stability quotients (ISQ) were determined by RFA
      measurements made at the time of fixture placement. Pearson's correlation
      analysis and Spearman's test were used to identify statistically significant
      correlations within the resultant data. Receiver operating characteristic (ROC)
      analysis was used to determine whether baseline ISQ values can accurately predict
      early implant failure. RESULTS: The mean baseline ISQ values for the two groups
      were 66.8 (experimental) and 66.2 (control). The 12-month survival rates were
      86.4% (experimental) and 100% (control). There were no statistically significant
      correlations between baseline ISQ values and early implant failure, bone quality
      variables, or implant dimension. ROC analysis showed that baseline ISQ values
      cannot predict early implant failure. CONCLUSION: Baseline RFA measurements were
      not able to predict early failure of immediately loaded implants placed in the
      posterior maxilla and therefore should not be used to determine whether an
      implant is a candidate for immediate nonfunctional loading in this region of the
      mouth.

PMID- 24325548
TI  - On the mismatch between population drinking and drink driving. Response to Gjerde
      et al.

PMID- 24325549
TI  - Membrane transport in the malaria parasite and its host erythrocyte.
AB  - As it grows and replicates within the erythrocytes of its host the malaria
      parasite takes up nutrients from the extracellular medium, exports metabolites
      and maintains a tight control over its internal ionic composition. These
      functions are achieved via membrane transport proteins, integral membrane
      proteins that mediate the passage of solutes across the various membranes that
      separate the biochemical machinery of the parasite from the extracellular
      environment. Proteins of this type play a key role in antimalarial drug
      resistance, as well as being candidate drug targets in their own right. This
      review provides an overview of recent work on the membrane transport biology of
      the malaria parasite-infected erythrocyte, encompassing both the parasite-induced
      changes in the membrane transport properties of the host erythrocyte and the cell
      physiology of the intracellular parasite itself.

PMID- 24325551
TI  - Retraction. IRAK1-independent pathways required for the interleukin-1-stimulated
      activation of the Tpl2 catalytic subunit and its dissociation from ABIN2.

PMID- 24325550
TI  - The role of the non-canonical Wnt-planar cell polarity pathway in neural crest
      migration.
AB  - The neural crest is an embryonic stem cell population whose migratory behaviour
      has been likened to malignant invasion. The neural crest, as does cancer,
      undergoes an epithelial-to-mesenchymal transition and migrates to colonize almost
      all the tissues of the embryo. Neural crest cells exhibit collective cell
      migration, moving in streams of high directionality. The migratory neural crest
      streams are kept in shape by the presence of negative signals in their vicinity.
      The directionality of the migrating neural crest is achieved by contact-dependent
      cell polarization, in a phenomenon called contact inhibition of locomotion. Two
      cells experiencing contact inhibition of locomotion move away from each other
      after collision. However, if the cell density is high only cells exposed to a
      free edge can migrate away from the cluster leading to the directional migration
      of the whole group. Recent work performed in chicks, zebrafish and frogs has
      shown that the non-canonical Wnt-PCP (planar cell polarity) pathway plays a major
      role in neural crest migration. PCP signalling controls contact inhibition of
      locomotion between neural crest cells by localizing different PCP proteins at the
      site of cell contact during collision and locally regulating the activity of Rho
      GTPases. Upon collision RhoA (ras homologue family member A) is activated,
      whereas Rac1 is inhibited at the contact between two migrating neural crest
      cells, leading to the collapse of protrusions and the migration of cells away
      from one another. The present review summarizes the mechanisms that control
      neural crest migration and focuses on the role of non-canonical Wnt or PCP
      signalling in this process.

PMID- 24325553
TI  - Values associated with public involvement in health and social care research: a
      narrative review.
AB  - BACKGROUND: Much has been written about public involvement (PI) in health and
      social care research, but underpinning values are rarely made explicit despite
      the potential for these to have significant influence on the practice and
      assessment of PI. OBJECTIVE: The narrative review reported here is part of a
      larger MRC-funded study which is producing a framework and related guidance on
      assessing the impact of PI in health and social care research. The review aimed
      to identify and characterize the range of values associated with PI that are
      central elements of the framework. METHODS: We undertook a review and narrative
      synthesis of diverse literatures of PI in health and social care research,
      including twenty existing reviews and twenty-four chapters in sixteen textbooks.
      RESULTS: Three overarching value systems were identified, each containing five
      value clusters. (i) A system concerned with ethical and/or political issues
      including value clusters associated with empowerment; change/action;
      accountability/transparency; rights; and ethics (normative values). (ii). A
      system concerned with the consequences of public involvement in research
      including value clusters associated with effectiveness; quality/relevance;
      validity/reliability; representativeness/objectivity/generalizability; and
      evidence (substantive values). (iii) A system concerned with the conduct of
      public involvement in including value clusters associated with
      Partnership/equality; respect/trust; openness and honesty; independence; and
      clarity (process values). CONCLUSION: Our review identified three systems
      associated with PI in health and social care research focused on normative,
      substantive and process values. The findings suggest that research teams should
      consider and make explicit the values they attach to PI in research and discuss
      ways in which potential tensions may be managed in order to maximize the benefits
      of PI for researchers, lay experts and the research.

PMID- 24325554
TI  - Fetuin-A, a new vascular biomarker of cognitive decline in older adults.
AB  - OBJECTIVES: Fetuin-A is an abundant plasma protein known to predict vascular
      disease. Fetuin-A levels are lower in patients with Alzheimer's disease in
      proportion to the severity of cognitive impairment, but their association with
      normal cognitive ageing is unknown. We evaluated the association of serum fetuin
      A levels with cognitive function in community-dwelling older adults.
      DESIGN/PATIENTS/MEASUREMENTS: A population-based study of 1382 older adults
      (median age 75) who had plasma fetuin-A levels and cognitive function evaluated
      in 1992-1996; 855 had repeat cognitive function assessment a median of 4 years
      later. RESULTS: Adjusting for age, sex, education and depression, higher levels
      of fetuin-A were associated with better baseline performance on the Mini-Mental
      Status Exam (MMSE; P = 0.012) and a tendency for better Trails Making B scores (P
      = 0.066). In longitudinal analyses, the likelihood of a major decline (highest
      decile of change) in Trails B was 29% lower (P = 0.010) for each SD higher
      baseline fetuin-A level; odds of major decline in MMSE was 42% lower (P = 0.005)
      per SD higher fetuin-A for individuals with no known CVD, but were not related to
      fetuin-A in those with CVD (P = 0.33). Fetuin-A was not related to Category
      Fluency performance. Results were independent of multiple vascular risk factors
      and comorbid conditions. CONCLUSIONS: Higher plasma fetuin-A concentrations are
      associated with better performance on tests of global cognitive function and
      executive function and with less likelihood of major decline in these cognitive
      abilities over a 4-year period. Fetuin-A may serve as a biological link between
      vascular disease and normal age-related cognitive decline.

PMID- 24325555
TI  - Tumor-penetrating peptide mediation: an effective strategy for improving the
      transport of liposomes in tumor tissue.
AB  - Currently, the inefficient transport of liposomes in tumor tissue hinders their
      clinical application. Tumor-penetrating peptides (TPP) are a series of targeting
      peptides with the function of penetrating tumor blood vessels and tumor stroma.
      This work aimed to improve the penetration of liposomes in tumor tissues by TPP
      modification, thereby enhancing the antitumor effect. First, RPARPAR, a TPP, was
      modified to the surface of liposomes loaded with doxorubicin. The RPARPAR
      modified liposomes (RPA-LP) and unmodified liposomes (LP) showed spherical
      morphology with average sizes about 90 nm. RPA-LP exhibited remarkably increased
      cellular accumulation by PC-3 tumor cells than LP as evidenced by the cellular
      uptake test. The in vivo imaging study confirmed that RPARPAR modification
      significantly increased the liposome accumulation in subcutaneous tumor tissues.
      RPA-LP could penetrate through tumor blood vessels and tumor stroma and into the
      deep tumor tissues as evidence by the immunofluorescence staining analysis. The
      cytotoxicity of RPARPAR-modified doxorubicin liposomes (RPA-LP-DXR) is
      considerably increased compared with that of doxorubicin liposomes (LP-DXR). The
      RPA-LP-DXR also showed significantly (p < 0.005) stronger growth-inhibiting
      effect on tumor than LP-DXR, possibly due to the tumor-penetrating ability of RPA
      LP and targeted killing of tumor cells. This study proved that TPP mediation may
      be an effective strategy for improving the transport of liposomes in tumor
      tissue. 

PMID- 24325556
TI  - Functional hepatocellular regeneration in elderly patients undergoing
      hepatectomy.
AB  - BACKGROUND & AIMS: More than 50% of liver tumours occur in patients aged 65 years
      or more. Assessment of functional liver regeneration capacity is crucial to
      minimize postoperative liver failure. We aimed to study functional hepatocellular
      regeneration, through scintigraphic quantification of Mebrofenin hepatic
      extraction fraction (HEF), after partial hepatectomy, comparing elderly patients
      with younger ones. METHODS: One hundred and two patients undergoing partial
      hepatectomy for primary or secondary hepatic lesions were prospectively included
      and divided in two groups: Group A - 58 patients aged <65 years (33 men, 53.9 +/-
      8.7 years), Group B - 44 patients aged >=65 years (32 men, 71 +/- 5 years).
      Groups were comparable in several aspects except for the presence of cirrhosis
      (more common in Group B, all patients Child-Pugh score A) and the initial
      diagnosis (Group B - primary lesions, Group A - metastases). The scintigraphic
      evaluation of Mebrofenin-HEF was performed before surgery, on the 5th and 30th
      day post-hepatectomy. RESULTS: Mortality and morbidity were 3.4 and 12.1%,
      respectively, in Group A and 2.3 and 11.4% in Group B (n.s.). HEF values (%),
      T1/2 (min) and Tmax (min) showed no significant differences between the two
      groups: Group A (preoperative: HEF = 99.2 +/- 1.5%, T1/2 = 36.7 +/- 21.3, Tmax =
      15 +/- 6. Day 5: HEF = 96.3 +/- 10.8%, T1/2 = 76.4 +/- 75.9; Tmax = 13.3 +/- 4.9.
      Day 30: HEF = 98.4 +/- 5.5%, T1/2 = 38.6 +/- 7.7, Tmax = 12.8 +/- 3.6) and Group
      B (preoperative: HEF = 95.3 +/- 13%, T1/2 = 38.1 +/- 24.1; Tmax = 15.9 +/- 9.4.
      Day 5: HEF = 98.4 +/- 2.6%, T1/2 = 106.6 +/- 131.7; Tmax = 15.1 +/- 6.2. Day 30:
      HEF = 99 +/- 2.1%, T1/2 = 40.5 +/- 27; Tmax = 15.5 +/- 6.7). CONCLUSION: Our
      results suggest that functional hepatocellular regeneration is early, fast and
      similar between elderly and younger patients. Thus, age alone, does not appear to
      represent an absolute contraindication to hepatectomy.

PMID- 24325558
TI  - Respecting Choices(r) and advance directives in a diverse community.
AB  - BACKGROUND: Respecting Choices(r) is a program designed and verified to improve
      advance care planning, yet it has not been tested in racially/ethnically diverse
      communities. Research has shown racial/ethnic minorities are less likely to have
      advance directives (ADs). OBJECTIVE: To determine whether Respecting Choices(r)
      would improve AD prevalence and utilization in a racially and ethnically diverse
      community. METHODS: The study design was that of a retrospective chart review.
      Subjects were all decedents from 2005 to 2010 (n=732) in a 300-bed Midwestern
      metropolitan hospital. Prevalence was assessed by the presence of an AD in the
      chart. Utilization was measured by the consistency of wishes expressed in an AD
      and treatment received ("No CPR," "No Feeding Tube," "No Antibiotics," "No
      Ventilator," "Comfort Care," and "Terminal Extubation"). Average treatment effect
      using regression analysis and matching on covariates was used for analysis of
      Respecting Choices(r) on AD prevalence. Proportional difference tests were used
      to compare consistency of wishes by race/ethnicity before and after Respecting
      Choices(r). RESULTS: The prevalence of ADs increased significantly for racial and
      ethnic minorities after the implementation of Respecting Choices(r): from 25.8%
      to 38.4% (p=0.011). The increase in AD prevalence for whites following Respecting
      Choices(r) was only marginal (46.7% to 47.3%; p=0.648), and the overall
      prevalence of ADs did not significantly change (35.9% to 42.9%; p=0.069).
      Consistency was high (74% to 96%) for all orders, and there were no significant
      differences following implementation of Respecting Choices(r) or between whites
      and racial and ethnic minorities. CONCLUSIONS: The prevalence of ADs increased
      after Respecting Choices(r) was initiated in a racially and ethnically diverse
      community.

PMID- 24325559
TI  - A case of recurrent bleeding stomal varix controlled using embolization with a
      liquid copolymer: an effective therapy for palliation.
AB  - BACKGROUND: Bleeding stomal varices (BSV) is a common problem in patients
      undergoing an ileostomy or colostomy. The diagnosis is often delayed as blood
      loss occurs in small amounts over a period of time, usually from minor
      anastamosing blood vessels at the ostomy site making it hard to diagnose.
      Treatment options can be limited in terms of modalities and efficacy. CASE: We
      describe a case of recurrent bleeding from a superior mesenteric vein (SMV) that
      was inadvertently sewn into the ileostomy site during surgery. Bleeding was
      initially controlled with percutaneous SMV coil embolization, but the bleeding
      persisted, only to be controlled finally by embolization using a liquid
      copolymer. Though the patient was terminally ill, his quality of life
      significantly improved thereafter, he did not have any further bleeding episodes
      during 10 months of follow-up. CONCLUSION: Embolization of a recurrent bleeding
      stomal varix with a liquid copolymer may be an effective therapeutic option.

PMID- 24325561
TI  - Who is my patient? Reflection of a trainee trying to play doctor.

PMID- 24325560
TI  - Transfusion in palliative cancer patients: a review of the literature.
AB  - BACKGROUND: Transfusion is not an exceptional circumstance in palliative cancer
      patients (PCPs). This makes it necessary to confront not only medical aspects but
      also those of infrastructure and ethical issues. On some occasions, literature
      needs to be consulted to work out the best approach in a patient's particular
      case. Our aim was to review the literature contained in PubMed and EMBASE so as
      to find out about the information available on transfusion in PCPs. METHODS: A
      search for literature was carried out in databases PubMed and EMBASE, using
      "transfusion," "cancer," "end-of-life care," "terminal care," and "palliative
      care" as key words. Publications were classified according to the main topic
      discussed (clinical, infrastructure, and ethics) and the information included in
      each article critically assessed. RESULTS: We found 334 articles but only 43 were
      considered valuable for the present study. Of these 43 articles, 21 deal with
      clinical topics while 12 deal with infrastructure and 10 with ethical issues.
      There is an absolute lack of randomized controlled trials or clinical guidelines.
      Trigger parameters for transfusion are not clearly established. Benefits of the
      procedure are shortly experienced and remain controversial. Home transfusions are
      encouraged, but this sole procedure has not been demonstrated to be cost
      effective. Different cultures, cases, and realities illustrate the diversity of
      the ethical management of transfusion in PCPs. DISCUSSION: Although transfusion
      is certainly a common practice in PCPs, there is a relative lack of literature on
      this topic. Publications are unconnected and hardly any prospective studies have
      been performed. A large part of the little literature available only concerns
      descriptive and very general aspects of the issue. As transfusional products and
      financial and human resources are finite, it would be desirable to establish
      clear research lines on the different aspects considered (clinical,
      infrastructure, and ethical) that can help clinicians, nurses, patients, and
      carers to make a decision.

PMID- 24325562
TI  - Do no harm.

PMID- 24325563
TI  - All hospice patients are not equal: development of a visit-based acuity index.
AB  - BACKGROUND: Although hospices need to be able to anticipate patient acuity, there
      are currently no published models that predict the frequency of visits that a new
      hospice patient is likely to receive. OBJECTIVES: To identify patient
      characteristics that are associated with the frequency of health care provider
      visits in the first 8 days of hospice care. METHODS: An electronic health record
      (EHR)-based retrospective cohort study was conducted in seven hospice programs in
      the United States. Participants were 35,232 patients who were admitted between
      October 1, 2008 and May 31, 2011 and received hospice care at home on the day of
      enrollment. The main outcome measure was the average number of visits per day by
      nurses, social workers, chaplains, and home health aides in the first 8 days of
      home hospice care (day of admission plus up to 7 subsequent days). RESULTS: In a
      mixed effects regression model, 14 independent predictors of visit frequency were
      identified. For instance, several demographic characteristics were associated
      with more frequent visits, as were lower Palliative Performance Scale (PPS)
      scores (<40: 1.78 visits/day, 95% confidence interval [CI] 1.74-1.82 versus 40
      60: 1.65 visits/day, 95% CI 1.61-1.69 versus >60: 1.41 visits/day, 95% CI 1.36
      1.47; p<0.001), the presence of pain (pain: 1.77 visits/day; 95% CI 1.72-1.82
      versus no pain: 1.44 visits/day, 95% CI .39-1.59; p<0.001). Patients admitted to
      home hospice from a hospital also received more frequent visits compared with
      other patients (hospital: 1.73 visits/day, 95% CI 1.67-1.79 versus home: 1.42
      visits/day, 95% CI 1.40-1.44; p<0.001). CONCLUSIONS: An acuity index based on
      these variables could help hospices to better anticipate patient needs and staff
      workload, and could be used to guide strategic planning as hospices take part in
      accountable care organizations (ACOs).

PMID- 24325564
TI  - Proximal disease extension and related predicting factors in ulcerative
      proctitis.
AB  - OBJECTIVE: Ulcerative colitis usually involves the rectum, may extend in a
      proximal and continuous fashion to involve varying portions of the bowel.
      However, the risk factors predictive of proximal extension have yet to be
      determined. The aim of this study was to evaluate both the natural course of
      disease and the risk factors influencing the proximal disease extension in
      ulcerative proctitis. MATERIAL AND METHODS: We retrospectively analyzed 98
      patients with ulcerative proctitis at the time of diagnosis who were regularly
      followed and underwent sigmoidoscopy or colonoscopy between January 2000 and
      December 2007. RESULTS: The mean duration of follow-up was 109.2 +/- 49.5 months.
      A total of 27 (27.6%) patients experienced proximal disease extension. Mayo
      scores were significantly higher in the extension group compared with patients
      whose ulcerative proctitis did not extend proximally (p < 0.001). Corticosteroid
      use at initial diagnosis was also more frequent in the extension group (p =
      0.026). In addition, chronic, continuous disease activation within 6 months of
      the initial diagnosis was significantly higher in the extension group (p <
      0.001), as was disease relapse and the number of hospitalizations over the entire
      follow-up period (p < 0.001 and p = 0.002). According to multivariate analysis,
      disease extension after the initial diagnosis was associated with chronic disease
      activation, disease relapse and hospitalization (p = 0.030, p = 0.042 and p =
      0.044, respectively). CONCLUSION: Increased severity of disease upon diagnosis of
      ulcerative proctitis was associated with a higher probability of proximal disease
      extension during the follow-up period. Moreover, those with disease extension
      were more likely to experience relapse and to be hospitalized, indicating poor
      prognosis.

PMID- 24325566
TI  - Cost-effectiveness of abatacept for moderate-to-severe rheumatoid arthritis.
AB  - Abatacept, a selective T-cell costimulation modulator, has become a valuable
      treatment option for those with moderately to severely active rheumatoid
      arthritis. Given new clinical evidence, for the first time guidelines from the
      American College of Rheumatology and Canadian Rheumatology Association are
      promoting the consideration of abatacept as the first biologic added to initial
      traditional disease-modifying antirheumatic drugs once an inadequate response to
      disease-modifying antirheumatic drug monotherapy has been established, putting
      abatacept at the same line of treatment options as TNF-alpha inhibitors or
      rituximab. Since the advent of the subcutaneous formulation of abatacept,
      positive results from its clinical trials have further increased its appeal. In
      light of these changes, a review of the literature was conducted on the cost
      effectiveness of abatacept for moderate-to-severe rheumatoid arthritis. Here we
      discuss current evidence, gaps in the literature and abatacept's future outlook. 

PMID- 24325565
TI  - TE-array--a high throughput tool to study transposon transcription.
AB  - BACKGROUND: Although transposable element (TE) derived DNA accounts for more than
      half of mammalian genomes and initiates a significant proportion of RNA
      transcripts, high throughput methods are rarely leveraged specifically to detect
      expression from interspersed repeats. RESULTS: To characterize the contribution
      of transposons to mammalian transcriptomes, we developed a custom microarray
      platform with probes covering known human and mouse transposons in both sense and
      antisense orientations. We termed this platform the "TE-array" and profiled TE
      repeat expression in a panel of normal mouse tissues. Validation with
      nanoString(r) and RNAseq technologies demonstrated that TE-array is an effective
      method. Our data show that TE transcription occurs preferentially from the sense
      strand and is regulated in highly tissue-specific patterns. CONCLUSIONS: Our
      results are consistent with the hypothesis that transposon RNAs frequently
      originate within genomic TE units and do not primarily accumulate as a
      consequence of random 'read-through' from gene promoters. Moreover, we find TE
      expression is highly dependent on the tissue context. This suggests that TE
      expression may be related to tissue-specific chromatin states or cellular
      phenotypes. We anticipate that TE-array will provide a scalable method to
      characterize transposable element RNAs.

PMID- 24325567
TI  - Norartocarpetin from a folk medicine Artocarpus communis plays a melanogenesis
      inhibitor without cytotoxicity in B16F10 cell and skin irritation in mice.
AB  - BACKGROUND: Many natural products used in preventive medicine have also been
      developed as cosmeceutical ingredients in skin care products, such as Scutellaria
      baicalensis and Gardenia jasminoides. Norartocarpetin is one of the antioxidant
      and antityrosinase activity compound in Artocarpus communis; however, the
      cytotoxicity, skin irritation and antimelanogenesis mechanisms of norartocarpetin
      have not been investigated yet. METHODS: In the present study, cell viability in
      vitro and skin irritation in vivo are used to determine the safety of
      norartocarpetin. The melanogenesis inhibition of norartocarpetin was determined
      by cellular melanin content and tyrosinase in B16F10 melanoma cell. Moreover, we
      examined the related-melanogenesis protein by western blot analysis for
      elucidating the antimelanogenesis mechanism of norartocarpin. RESULTS: The result
      of the present study demonstrated that norartocarpetin not only present non
      cytotoxic in B16F10 and human fibroblast cells but also non-skin irritation in
      mice. Moreover, our result also first found that norartocarpetin downregulated
      phospho-cAMP response element-binding (phospho-CREB) and microphthalmia
      associated transcription factor (MITF) expression, which in turn decreased both
      synthesis of tyrosinases (TRP-1 and TRP-2) and cellular melanin content. This
      process is dependent on norartocarpetin phosphorylation by mitogen-activated
      protein kinases such as phospho-JNK and phospho-p38, and it results in decreased
      melanogenesis. CONCLUSION: The present study suggests that norartocarpetin could
      be used as a whitening agent in medicine and/or cosmetic industry and need
      further clinical study.

PMID- 24325568
TI  - Bisphenol A in domestic and imported canned foods in Japan.
AB  - Bisphenol A (BPA) concentrations were surveyed in 100 domestic and 60 imported
      canned foods purchased from the Japanese market in 2011-12. BPA was extracted
      from the canned foods, derivatised by ethylation and analysed using GC-MS. In the
      domestic canned foods, the maximum and average BPA concentrations were 30 and 3.4
      ng g(-1), respectively, while in the imported canned foods they were 390 and 57
      ng g(-1), respectively. The BPA level in the domestic canned foods was
      significantly lower than that in the imported canned foods. Based on these
      results, the intakes of BPA from the domestic and imported canned foods in Japan
      were estimated as 644 ng person(-1) day(-1). The Japanese BPA intake was the
      second lowest following New Zealand, although imported canned foods increased. It
      was sufficiently lower than the tolerable daily intake of EFSA and the USEPA. The
      drastic reduction of BPA in the domestic canned foods should be due to the 'BPA
      reduced cans' that Japanese can manufacturers had developed in the late 1990s and
      became widely used in Japan.

PMID- 24325569
TI  - Radiographic response to neoadjuvant therapy and its impact on scope of surgery
      and prognosis in stage IIB/III soft tissue sarcomas.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy has been newly included in the NCCN
      guidelines as a treatment option for stage IIB/III soft tissue sarcomas. Whether
      radiographic response to neoadjuvant therapy correlates with improved quality of
      resection and prognosis remains unproven. METHODS: Data from 120 consecutive
      patients who were treated with neoadjuvant chemoradiotherapy followed by surgical
      resection for their locally aggressive limb sarcomas were retrospectively
      reviewed. Radiographic response was evaluated after neoadjuvant therapy according
      to Response Evaluation Criteria In Solid Tumors, and data was analyzed for
      overall survival (OS), local recurrence free survival (LRFS) and metastasis free
      survival (MFS). Surgical complications and toxicities, as well as functional
      outcomes, were also analysed. RESULTS: After neoadjuvant chemoradiotherapy, 25
      patients (20.8%) had a partial response, 75 patients (62.5%) had stable disease,
      and 20 patients (16.7%) showed disease progression. Radiographic response to
      neoadjuvant therapy correlated significantly with improved OS (P = 0.002) and MFS
      (P < 0.001). Patients with partial response (PR) had a significantly decreased
      rate of R2 resection as compared with stable disease (SD) and progressive disease
      (PD) patients (4.0% Vs 21.4%, P < 0.001). CONCLUSIONS: Radiographic response to
      neoadjuvant chemoradiotherapy correlates with improved quality of resection and
      prognosis in extremity STS patients.

PMID- 24325570
TI  - Pro-inflammatory cytokine release and cell growth inhibition in primary human
      oral cells after exposure to endodontic sealer.
AB  - AIM: To assay the toxicity of the single-methacrylate-based sealer urethane
      dimethacrylate (UDMA) (EndoRez) in terms of cell growth and pro-inflammatory
      cytokines release, in expanded ex vivo human dental pulp stem cells (hDPSCs),
      human periodontal ligament stem cells (hPDLSCs), human gingival fibroblasts
      (hGFs) and human osteoblasts (hOSTs). METHODOLOGY: Dental pulp and periodontal
      ligament stem cells, osteoblasts and fibroblasts were derived from five young
      donors. After in vitro isolation, hDPSCs, hPDLSCs, hGFs and hOSTs were seeded to
      resin-based sealers for 24, 48, 72 h up to 1 week. The morphological features and
      the cell growth and the release of pro-inflammatory interleukin (IL)6, IL8, IL12
      and tumour necrosis factor (TNF) alpha were analysed. Differences in cell growth
      and in interleukin secretion were analysed for statistical significance with two
      way anova tests for multiple comparisons. RESULTS: Exposure to endodontic sealer
      based on UDMA resulted in a 50% decrease in survival oral cells at 24 h of
      incubation. No evident morphological changes were present in cell cultures
      examined. After 48 h, 72 h and 1-week culture time, a progressive cell growth was
      evident. A significant up-regulation of IL6, IL8, IL12 and TNFalpha cytokines in
      cells in contact with the dental sealer compared to the control was observed.
      CONCLUSION: In vitro, EndoRez interacted with primary human hDPSCs, hPDLSCs, hGFs
      and hOSTs causing damage to biological system evidenced through cell growth
      inhibition and up-regulation of IL6, IL8, IL12 and TNFalpha proinflammatory
      mediators.

PMID- 24325571
TI  - Ascorbic acid enhances adipogenesis of 3T3-L1 murine preadipocyte through
      differential expression of collagens.
AB  - BACKGROUND: Adipogenesis from preadipocytes into mature adipocyte is precisely
      coordinated by transcription factors such as CCAAT-enhancer-binding proteins
      (C/EBPs) and peroxisome proliferator-activated receptor gamma (PPARgamma),
      cytokines, and hormones, which is accompanied by extracellular matrix remodeling.
      Besides anti-oxidant activity, ascorbic acid (ASC) is participating in collagen
      biosynthesis and increase production and processing of collagens. Moreover,
      several studies demonstrated that ASC enhanced differentiation from preadipocytes
      into mature adipocytes. METHODS: The adipogenic effect of ascorbic acid was
      evaluated in chemical induced 3T3-L1 by Oil Red O staining. This effect was
      elucidated by immunoblotting which detected the expression level of collagens and
      transcription factors in adipogenesis. The immunocytochemical determination of
      type I collagen was performed in 3T3-L1 adipocyte to show the change of
      extracellular matrix during adipogenesis. RESULTS: In this study, Oil Red O
      staining in 3T3-L1 preadipocytes was increased dose-dependently by addition of
      ASC. These ASC-treated adipocytes increased collagen processing of alpha1(I) and
      alpha1(V) and expressed alpha1(VI) and alpha2(VI) collagens differentially. ASC
      also stimulated expression of C/EBPalpha and PPARgamma, which is preceded by
      collagen enhancement. In addition, inhibition of ASC activity by ethyl-3,4
      dihydroxybenzoate showed reduction of lipid accumulation by removal of large
      lipid droplets, not by inhibition of lipid production. This observation went with
      loss of alpha1(I) deposition on adipocyte surface, increase of alpha1(V) and
      alpha2(VI) collagens and decrease of C/EBPs. CONCLUSION: Our findings imply that
      various actions of ASC on adipogenesis through differential collagen expression
      may provide diverse applications of ASC to adipose tissue technology.

PMID- 24325572
TI  - Bone quality evaluation at dental implant site using multislice CT, micro-CT, and
      cone beam CT.
AB  - OBJECTIVES: The first purpose of this study was to analyze the correlation
      between bone volume fraction (BV/TV) and calibrated radiographic bone density
      Hounsfield units (HU) in human jaws, derived from micro-CT and multislice
      computed tomography (MSCT), respectively. The second aim was to assess the
      accuracy of cone beam computed tomography (CBCT) in evaluating trabecular bone
      density and microstructure using MSCT and micro-CT, respectively, as reference
      gold standards. MATERIAL AND METHODS: Twenty partially edentulous human
      mandibular cadavers were scanned by three types of CT modalities: MSCT (Philips,
      Best, the Netherlands), CBCT (3D Accuitomo 170, J Morita, Kyoto, Japan), and
      micro-CT (SkyScan 1173, Kontich, Belgium). Image analysis was performed using
      Amira (v4.1, Visage Imaging Inc., Carlsbad, CA, USA), 3Diagnosis (v5.3.1,
      3diemme, Cantu, Italy), Geomagic (studio((r)) 2012, Morrisville, NC, USA), and
      CTAn (v1.11, SkyScan). MSCT, CBCT, and micro-CT scans of each mandible were
      matched to select the exact region of interest (ROI). MSCT HU, micro-CT BV/TV,
      and CBCT gray value and bone volume fraction of each ROI were derived.
      Statistical analysis was performed to assess the correlations between
      corresponding measurement parameters. RESULTS: Strong correlations were observed
      between CBCT and MSCT density (r = 0.89) and between CBCT and micro-CT BV/TV
      measurements (r = 0.82). Excellent correlation was observed between MSCT HU and
      micro-CT BV/TV (r = 0.91). However, significant differences were found between
      all comparisons pairs (P < 0.001) except for mean measurement between CBCT BV/TV
      and micro-CT BV/TV (P = 0.147). CONCLUSIONS: An excellent correlation exists
      between bone volume fraction and bone density as assessed on micro-CT and MSCT,
      respectively. This suggests that bone density measurements could be used to
      estimate bone microstructural parameters. A strong correlation also was found
      between CBCT gray values and BV/TV and their gold standards, suggesting the
      potential of this modality in bone quality assessment at implant site.

PMID- 24325573
TI  - Dignity and respect: facilitating meaningful occupation for SeSotho elders.
AB  - AIM: Frail and vulnerable adults are divested of meaningful encounters when
      modernization and urbanization force them to embrace an unconventional
      residential care environment as a home. The aim of this article is to report on a
      study of SeSotho elders living in residential care to illustrate how more
      meaningful and culturally relevant experiences could be facilitated for them.
      METHODS: A content analysis was done of the individual opinions of 15
      collaborators as a secondary scrutiny of information obtained during a nominal
      group process. MAJOR FINDINGS. Findings revealed that elders were prone to
      experience loneliness, helplessness, and boredom due to situations dominated by
      occupational injustice. Co-occupations, training of staff, and environmental
      adaptations that allow a sense of interdependence could contribute in
      facilitating occupational justice for elders from a traditional South African
      indigenous background living in residential care. PRINCIPAL CONCLUSION: Human
      dignity and respect are upheld within residential care when elders have access to
      purposeful and meaningful activities of their choice that are culturally
      appropriate. Occupational therapists should advocate for doing, belonging, and
      becoming by facilitating meaningful occupational participation that is culturally
      relevant for their clients.

PMID- 24325574
TI  - Facing temptation in the bar: counteracting the effects of self-control failure
      on young adults' ad libitum alcohol intake.
AB  - BACKGROUND AND AIMS: The self-control strength model suggests that exertion of
      self-control leads to poorer subsequent self-control performance. Failure of self
      control has been suggested as an important underlying mechanism of excessive
      drinking. This study tested the effects of self-control failure on ad libitum
      drinking, and the potential moderating role of glucose and self-awareness on this
      relationship. DESIGN: The current research examined in two experiments whether
      the effects of self-control failure were different for males and females, and
      whether glucose (experiment 1) and self-awareness (experiment 2) would counteract
      the effects of self-control failure. A between-participants design with four
      conditions was employed in each experiment. SETTING: A semi-naturalistic drinking
      setting in the form of a laboratory bar. PARTICIPANTS: Undergraduate students
      recruited at Radboud University Nijmegen, the Netherlands (experiment 1: n = 106;
      experiment 2: n = 108). MEASUREMENTS: The total amount of alcohol consumed during
      an experimental break (observational data) and questionnaire data on drinking
      patterns. FINDINGS: Self-control failure led to increased levels of drinking in
      males (P < 0.05), whereas females drank less after being depleted (P < 0.01).
      Self-awareness, but not glucose, was found to counteract the effects of self
      control failure among males (P < 0.05). CONCLUSIONS: Self-control failure leads
      to increased drinking of alcohol in males and decreased levels of drinking
      alcohol in females. However, increasing self-awareness appears to be a promising
      strategy in facing the temptation to drink when cognitive resources to inhibit
      intake are low.

PMID- 24325576
TI  - Preparation, optimization and characterization of bovine lactoferrin-loaded
      liposomes and solid lipid particles modified by hydrophilic polymers using
      factorial design.
AB  - Bioadhesive liposomes and solid lipid particles (SLPs) modified by pectin and
      chitosan for oral administration of bovine lactoferrin (bLf) were prepared using
      a 2(4) full-factorial design to identify the key formulation variables
      influencing particle size and drug entrapment efficiency (EE). Netlike structures
      of the polymer-particle mixture consisting of a polymeric network in which
      multiple particles were imbedded were observed by scanning electron microscopy
      (SEM). Chemical stability of bLf after encapsulation into pectin- and chitosan
      modified liposomes and SLPs was confirmed by Fourier transform infrared spectra
      (FTIR). Bovine lactoferrin was located within phospholipid bilayer, whereas in
      SLPs bLf was within the matrix. The crystalline nature of bLf after encapsulation
      was investigated by differential scanning calorimetry (DSC) of drug-loaded
      particles, indicating amorphous dispersion of bLf in the polymer-lipid matrix of
      pectin- and chitosan-modified liposomes and SLPs. In vivo pharmacokinetic
      investigation of bLf in pectin- and chitosan-modified liposomes and SLPs showed
      prolonged mean residence time (MRT) of bLf in rat blood and increased the
      relative bioavailability (Fbio %) by 1.95- to 2.69-fold compared with free bLf.
      The developed carrier systems are considered to be promising vehicles for oral
      delivery. 

PMID- 24325575
TI  - The Juvenile Diabetes Research Foundation Network for Pancreatic Organ Donors
      with Diabetes (nPOD) Program: goals, operational model and emerging findings.
AB  - nPOD actively promotes a multidisciplinary and unbiased approach toward a better
      understanding of T1D and identify novel therapeutic targets, through its focus on
      the study of human samples. Unique to this effort is the coordination of
      collaborative efforts and real-time data sharing. Studies supported by nPOD are
      providing direct evidence that human T1D isa complex and heterogeneous disease,
      in which a multitude of pathogenic factors may be operational and may contribute
      to the onset of the disease. Importantly, the concept that beta cell destruction
      is almost completed and that the autoimmune process is almost extinguished soon
      after diagnosis is being challenged. nPOD investigators are exploring the
      hypothesis that beta cell dysfunction may also be a significant cause of
      hyperglycemia, at least around the time of diagnosis, and are uncovering novel
      molecules and pathways that are linked to the pathogenesis and etiology of human
      T1D. The validation of therapeutic targets is also a key component of this
      effort, with recent and future findings providing new strategic direction for
      clinical trials.

PMID- 24325578
TI  - Synthesis and characterization of a novel series of agonist compounds as
      potential radiopharmaceuticals for imaging dopamine D2/3 receptors in their high
      affinity state.
AB  - Imaging of dopamine D2/3 receptors (D2/3R) can shed light on the nature of
      several neuropsychiatric disorders in which dysregulation of D2/3R signaling is
      involved. Agonist D2/3 tracers for PET/SPECT imaging are considered to be
      superior to antagonists because they are more sensitive to dopamine
      concentrations and may selectively label the high-affinity receptor state. Carbon
      11-labeled D2/3R agonists have been developed, but these short-lived tracers can
      be used only in centers with a cyclotron. Here, we report the development of a
      series of novel D2R agonist compounds based on the 2-aminomethylchromane (AMC)
      scaffold that provides ample opportunities for the introduction of longer-lived
      [(18)F] or [(123)I]. Binding experiments showed that several AMC compounds have a
      high affinity and selectivity for D2/3R and act as agonists. Two fluorine
      containing compounds were [(18)F]-labeled, and both displayed specific binding to
      striatal D2/3R in rat brain slices in vitro. These findings encourage further in
      vivo evaluations. 

PMID- 24325577
TI  - Tumor necrosis factor-alpha accelerates the resolution of established pulmonary
      fibrosis in mice by targeting profibrotic lung macrophages.
AB  - Idiopathic pulmonary fibrosis (IPF) is a relentless, fibrotic parenchymal lung
      disease in which alternatively programmed macrophages produce profibrotic
      molecules that promote myofibroblast survival and collagen synthesis. Effective
      therapies to treat patients with IPF are lacking, and conventional therapy may be
      harmful. We tested the hypothesis that therapeutic lung delivery of the
      proinflammatory cytokine tumor necrosis factor (TNF)-alpha into wild-type
      fibrotic mice would reduce the profibrotic milieu and accelerate the resolution
      of established pulmonary fibrosis. Fibrosis was assessed in bleomycin-instilled
      wild-type and TNF-alpha(-/-) mice by measuring hydroxyproline levels, static
      compliance, and Masson's trichrome staining. Macrophage infiltration and
      programming status was assessed by flow cytometry of enzymatically digested lung
      and in situ immunostaining. Pulmonary delivery of TNF-alpha to wild-type mice
      with established pulmonary fibrosis was found to reduce their fibrotic burden, to
      improve lung function and architecture, and to reduce the number and programming
      status of profibrotic alternatively programmed macrophages. In contrast, fibrosis
      and alternative macrophage programming were prolonged in bleomycin-instilled TNF
      alpha(-/-) mice. To address the role of the reduced numbers of alternatively
      programmed macrophages in the TNF-alpha-induced resolution of established
      pulmonary fibrosis, we conditionally depleted macrophages in MAFIA (MAcrophage
      Fas-Induced Apoptosis) mice. Conditional macrophage depletion phenocopied the
      resolution of established pulmonary fibrosis observed after therapeutic TNF-alpha
      delivery. Taken together, our results show for the first time that TNF-alpha is
      involved in the resolution of established pulmonary fibrosis via a mechanism
      involving reduced numbers and programming status of profibrotic macrophages. We
      speculate that pulmonary delivery of TNF-alpha or augmenting its signaling
      pathway represent a novel therapeutic strategy to resolve established pulmonary
      fibrosis. 

PMID- 24325580
TI  - A multidimensional model of optimal participation of children with physical
      disabilities.
AB  - PURPOSE: To present a conceptual model of optimal participation in recreational
      and leisure activities for children with physical disabilities. METHODS: The
      conceptualization of the model was based on review of contemporary theories and
      frameworks, empirical research and the authors' practice knowledge. A case
      scenario is used to illustrate application to practice. RESULTS: The model
      proposes that optimal participation in recreational and leisure activities
      involves the dynamic interaction of multiple dimensions and determinants of
      participation. The three dimensions of participation are physical, social and
      self-engagement. Determinants of participation encompass attributes of the child,
      family and environment. Experiences of optimal participation are hypothesized to
      result in long-term benefits including better quality of life, a healthier
      lifestyle and emotional and psychosocial well-being. CONCLUSION: Consideration of
      relevant child, family and environment determinants of dimensions of optimal
      participation should assist children, families and health care professionals to
      identify meaningful goals and outcomes and guide the selection and implementation
      of innovative therapy approaches and methods of service delivery. Implications
      for Rehabilitation Optimal participation is proposed to involve the dynamic
      interaction of physical, social and self-engagement and attributes of the child,
      family and environment. The model emphasizes the importance of self-perceptions
      and participation experiences of children with physical disabilities. Optimal
      participation may have a positive influence on quality of life, a healthy
      lifestyle and emotional and psychosocial well-being. Knowledge of child, family,
      and environment determinants of physical, social and self-engagement should
      assist children, families and professionals in identifying meaningful goals and
      guiding innovative therapy approaches.

PMID- 24325579
TI  - Long-term outcomes of chronic hepatitis B virus infection in the era of antiviral
      therapy in Korea.
AB  - BACKGROUND AND AIMS: Chronic hepatitis B (CHB) can progress to cirrhosis,
      hepatocellular carcinoma (HCC), and ultimately liver-related deaths. Recently,
      owing to potent antiviral therapy with minimal side-effects, sustained
      suppression of hepatitis B virus replication can be achieved, thereby preventing
      such complications. We aimed to reappraise clinical courses regarding disease
      progression in the era of antiviral therapy. METHODS: Between 2001 and 2005,
      treatment-naive Korean CHB patients without cirrhosis were enrolled and followed
      up for at least 5 years. During follow up, antiviral therapy was commenced
      according to Korean Association for the Study of the Liver guidelines, if
      eligible, and ultrasonography and laboratory and clinical assessment were
      performed regularly. Primary end-points were development of cirrhosis, hepatic
      decompensation, HCC, or liver-related deaths. RESULTS: Of 360 patients, 323
      (89.7%) received antiviral therapy such as lamivudine (70.6%), entecavir (8.7%),
      or telbivudine (6.5%). During follow up, cirrhosis developed in 29 (8.1%),
      hepatic decompensation in 4 (1.1%), and HCC in 15 (4.2%) patients. Annual
      incidences of cirrhosis, hepatic decompensation, and HCC were 1.05%, 0.14%, and
      0.53% per person-year, respectively. Age was an independent predictor for
      developing cirrhosis (hazard ratio [HR] 1.075, 95% confidence interval [CI] 1.037
      1.116; P < 0.001), whereas age (HR 1.060, 95% CI 1.012-1.111; P = 0.014) and
      cirrhosis (HR 17.470, 95% CI 5.081-60.063; P < 0.001) were those for developing
      HCC. CONCLUSIONS: In the era of antiviral therapy, overall clinical courses have
      been much improved since introduction of lamivudine in 1999. However, patients
      with older age or cirrhosis are still subject to HCC development despite
      appropriate antiviral therapy, necessitating cautious surveillance.

PMID- 24325581
TI  - "What do you expect from physiotherapy?": a detailed analysis of goal setting in
      physiotherapy.
AB  - PURPOSE: Health care practice guidelines require physiotherapists to include
      patients in goal-setting. However, not much is known about how this process is
      accomplished in practice. The purpose of this study is to analyse patient
      physiotherapist consultations and to identify how physiotherapists enquire about
      goals and how patients respond to these enquiries. METHOD: 37 consenting patients
      and their physiotherapist from outpatient physiotherapy practice settings were
      videotaped. Conversation analysis was used to transcribe and analyse the data.
      RESULTS: In 11 cases, physiotherapists enquire explicitly about goals. Patients'
      responses indicate that problems can arise when therapists' questions treat it as
      expected that the patient has a goal already in mind, and has sufficient
      understanding about "physiotherapy-relevant" goals. Patients' difficulties with
      stating a goal are related to patients' knowledge to propose a goal and whether
      they treat consultations as one in which it is appropriate to claim knowledge
      about goals. CONCLUSIONS: Goal-setting is not a straightforward process.
      Practices that entail asking patients to state their goals neither take into
      consideration the fact that patients may not know what an achievable goal is nor
      do they consider so-called social reasons for patients not to make claims to
      their physiotherapist about what the goals should be. Implications for
      Rehabilitation Patients respond to explicit goal enquiries using an open question
      with delayed responses indicating some communication problem. Goal-setting should
      not be treated as a predetermined process, but as negotiated in consultations.
      Goal-setting is a complex interaction in which participants manage knowledge
      about goals.

PMID- 24325583
TI  - Formation of hydrogen polyoxides as constituents of peroxy radical condensate
      upon low-temperature interaction of hydrogen atoms with liquid ozone.
AB  - The composition of low-temperature condensates obtained by the reaction of
      hydrogen atoms with liquid ozone has been determined from the Raman spectra and
      data on the molar ratio of O2 to H2O2 in the decomposition products. The main
      constituents are hydrogen tetroxide H2O4, trioxide H2O3, and peroxide H2O2 in
      comparable amounts and also water H2O. The mechanism and quantitative kinetic
      model of their formation have been proposed. H2O4, H2O3, and H2O2 are formed in
      the diffusion-controlled reactions between OH and HO2 in the liquid ozone layer
      and stabilized by transfer to the solid phase. OH and HO2 radicals are generated
      via a sequence of the reactions initiated by the interaction H + O3(liq). The
      model adequately reproduces the properties of the real condensates. 

PMID- 24325582
TI  - Asymptomatic bacteriuria is an independent predictor of urinary tract infections
      in an ambulatory cirrhotic population: a prospective evaluation.
AB  - BACKGROUND & AIMS: Asymptomatic bacteriuria (ASB) is a risk factor for urinary
      tract infections (UTIs) in many patients without liver disease. It remains
      unclear whether a diagnosis of ASB in an outpatient with cirrhosis could be
      utilized to predict the subsequent development of a UTI. We undertook this study
      to determine the prevalence and incidence of ASB in an outpatient population and
      its association with UTI. METHODS: We prospectively evaluated 108 adult
      outpatients with cirrhosis over a 6-month period. Monthly midstream urines (MSU)
      were performed to detect the occurrence of UTI and ASB (culture of >=10(8) CFU/L
      of a urinary pathogen in the absence of UTI symptoms). RESULTS: Of 108 patients
      enrolled, 99 completed at least one MSU, for a total of 489 MSUs. Total follow-up
      was 44 person-years. The incidences of ASB and UTI were 181 and 250 per 1000
      person-years, respectively. The prevalences of ASB and UTI on the first MSU were
      5 and 1%, respectively. In total, 8% of patients developed an episode of ASB and
      11% developed a UTI during the study period. Univariate predictors of UTI were
      female gender, primary biliary cirrhosis, number of previous UTIs and preceding
      ASB. Preceding ASB was the only independent predictor of UTI on multivariate
      analysis, with an odds ratio of 6.2 (1.1-34.3), P = 0.04. CONCLUSIONS: Cirrhotic
      patients have higher rates of ASB and UTI than reported in the general
      population. ASB is an independent predictor of UTI. Further studies are necessary
      to determine whether routine screening and antimicrobial treatment of ASB is
      warranted.

PMID- 24325584
TI  - Plasma irisin depletion under energy restriction is associated with improvements
      in lipid profile in metabolic syndrome patients.
AB  - OBJECTIVE: A recently discovered myokine, irisin, may have an important role in
      energy metabolism. This study aimed to evaluate the relationship between this
      hormone and the lipid profile of patients with metabolic syndrome (MetS)
      following a hypocaloric diet. DESIGN: Ninety-three Caucasian adults (52 men/41
      women) diagnosed with MetS followed an 8-week-long energy-restricted programme (
      30% of the energy requirements). Anthropometric measurements, biochemical markers
      and plasma irisin levels were analysed before and after the nutritional
      intervention. RESULTS: Global plasma irisin levels were significantly reduced at
      the end of the study (-72.0 +/- 100.9 ng/ml, P < 0.001) accompanying the weight
      loss (-6.9%). The depletion of irisin significantly correlated with changes in
      some atherogenic-related variables: total cholesterol (B = 0.106, P = 0.018),
      total cholesterol/high-density lipoprotein cholesterol ratio (B = 0.002, P =
      0.036), low-density lipoprotein cholesterol (B = 0.085, P = 0.037) and
      apolipoprotein B (B = 0.052, P = 0.002), independently of changes in body weight.
      CONCLUSIONS: An association between the reduction in plasma irisin levels and the
      depletion of important lipid metabolism biomarkers was observed in patients with
      MetS undergoing an energy-restricted programme.

PMID- 24325585
TI  - Effect of prophylactic 360 degrees  laser treatment for prevention of retinal
      detachment after phacovitrectomy: (Prophylactic 360 degrees  laser treatment for
      prevention of retinal detachment).
AB  - BACKGROUND: To investigate the effect of intraoperative 360 degrees  laser
      retinopexy anterior to the equator for the prevention of retinal detachment after
      phacovitrectomy. METHODS: The patients were part of two consecutive case series
      cohorts in macular hole (MH) and rhegmatogenous retinal detachment (RRD), one
      which did not receive intraoperative prophylactic 360 degrees  laser, and one
      which received intraoperative prophylactic 360 degrees  laser. For the 360
      degrees  laser treatment group, three rows of medium-white burns were positioned
      anterior to the equator. The baseline characteristics and the risk of retinal
      detachment over time were analyzed and compared between the groups. RESULTS:
      Prophylactic intraoperative 360 degrees  laser treatment was performed on 77 MH
      cases (67.3 years) and compared to a control group of 35 MH cases (65.8 years).
      Additionally, prophylactic intraoperative 360 degrees  laser treatment was
      performed on 108 RRD cases (64.0 years) and compared to 270 RRD cases (64.4
      years). The 360 degrees  laser group showed a significant reduction (0%, 0/77
      eyes) in the rate of the incidence of retinal detachment after vitrectomy at 12
      months after surgery in MH cases, compared with the control group (5.7%, 2/35
      eyes) (p = 0.034). Kaplan-Meier survival analysis demonstrated that the rate of
      retinal detachment in the control group was significantly higher than that in the
      360 degrees  laser group (p = 0.035). There was no significant difference between
      the groups in RRD cases (p = 0.092). CONCLUSIONS: Intraoperative 360 degrees 
      laser retinopexy following phacovitrectomy resulted in a significant reduction in
      the rate of postoperative retinal detachment in MH cases.

PMID- 24325587
TI  - Expression of AIM2 is high and correlated with inflammation in hepatitis B virus
      associated glomerulonephritis.
AB  - BACKGROUND & AIMS: Innate immunity is the first line of defense against invasive
      microbial infection, and AIM2 plays an important role in this process by sensing
      double-stranded DNA viruses. However, the role of AIM2 in regulating the immune
      response to viruses in vivo, especially in sensing hepatitis B virus (HBV), has
      not been examined. We hypothesized that the expression of AIM2 increases
      corresponding to HBV-mediated inflammation in patients with hepatitis B virus
      associated glomerulonephritis (HBV-GN), a condition which activates inflammatory
      mechanisms and causes renal damage. To test this hypothesis, we analyzed the
      expression of AIM2 in HBV-GN patients in relation to the inflammatory response to
      HBV infection. METHODS: A total of 79 patients diagnosed with chronic nephritis
      (CN) were enrolled in this study, including 54 HBV-GN patients as the
      experimental group and 24 chronic glomerulonephritis (CGN) patients as the
      negative control group. Six patients diagnosed with chronic hepatitis B (CHB)
      were also enrolled as positive controls. Each CN patient received renal biopsy,
      and immunohistochemistry was used to detect the expression of AIM2 and
      inflammatory factors caspase-1 and IL-1beta in the biopsy specimens. CHB patients
      received liver puncture biopsy, and immunohistochemistry was used to detect the
      expression of AIM2 in these specimens. Expression of AIM 2 among different groups
      and in relation to inflammatory factors caspase-1 and IL-1beta was analyzed.
      RESULTS: The expression of AIM2 in HBV-GN patients (81.4%) was significantly
      higher than in CGN patients (4.0%). Among the HBV-GN patients, expression of AIM2
      was significantly higher in the high HBV replication group than in the low HBV
      replication group. AIM2 expression was not correlated with age, gender, HBeAg
      status in serum, HBV-antigen type deposited in renal tissue or pathological type
      of HBV-GN. However, AIM2 levels were positively correlated with the expression of
      caspase-1 and IL-1beta in HBV-GN patients. The data suggest that AIM2 expression
      is directly correlated with HBV infection-associated inflammation. CONCLUSION:
      The elevation of AIM2 during HBV infection or replication may contribute to its
      associated inflammatory damage, thus providing a putative therapeutic target and
      a new avenue for researching the pathogenesis of HBV-GN.

PMID- 24325588
TI  - Whole transcriptome characterization of the effects of dehydration and
      rehydration on Cladonia rangiferina, the grey reindeer lichen.
AB  - BACKGROUND: Lichens are symbiotic organisms with a fungal and an algal or a
      cyanobacterial partner. Lichens inhabit some of the harshest climates on earth
      and most lichen species are desiccation-tolerant. Lichen desiccation-tolerance
      has been studied at the biochemical level and through proteomics, but the
      underlying molecular genetic mechanisms remain largely unexplored. The objective
      of our study was to examine the effects of dehydration and rehydration on the
      gene expression of Cladonia rangiferina. RESULTS: Samples of C. rangiferina were
      collected at several time points during both the dehydration and rehydration
      process and the gene expression intensities were measured using a custom DNA
      microarray. Several genes, which were differentially expressed in one or more
      time points, were identified. The microarray results were validated using qRT-PCR
      analysis. Enrichment analysis of differentially expressed transcripts was also
      performed to identify the Gene Ontology terms most associated with the
      rehydration and dehydration process. CONCLUSIONS: Our data identify differential
      expression patterns for hundreds of genes that are modulated during dehydration
      and rehydration in Cladonia rangiferina. These dehydration and rehydration events
      clearly differ from each other at the molecular level and the largest changes to
      gene expression are observed within minutes following rehydration. Distinct
      changes are observed during the earliest stage of rehydration and the mechanisms
      not appear to be shared with the later stages of wetting or with drying. Several
      of the most differentially expressed genes are similar to genes identified in
      previous studies that have investigated the molecular mechanisms of other
      desiccation-tolerant organisms. We present here the first microarray experiment
      for any lichen species and have for the first time studied the genetic mechanisms
      behind lichen desiccation-tolerance at the whole transcriptome level.

PMID- 24325589
TI  - (18)F-glyco-RGD peptides for PET imaging of integrin expression: efficient
      radiosynthesis by click chemistry and modulation of biodistribution by
      glycosylation.
AB  - Glycosylation frequently improves the biokinetics and clearance properties of
      macromolecules in vivo and could therefore be used for the design of
      radiopharmaceuticals for positron emission tomography (PET). Recently, we have
      developed a click chemistry method for (18)F-fluoroglycosylation of alkyne
      bearing RGD-peptides targeting the integrin receptor. To investigate whether this
      strategy could yield an (18)F-labeled RGD glycopeptide with favorable
      biokinetics, we generated a series of new RGD glycopeptides, varying the 6
      fluoroglycosyl residue from monosaccharide to disaccharide units, which provided
      the glucosyl ([(19)F]6Glc-RGD, 4b), galactosyl ([(19)F]Gal-RGD, 4c), maltosyl
      ([(19)F]Mlt-RGD, 4e), and cellobiosyl ([(19)F]Cel-RGD, 4f) conjugated peptides in
      high yields and purities of >97%. All of these RGD glycopeptides showed high
      affinity to alphavbeta3 (11-55 nM), alphavbeta5 (6-14 nM), and to alphavbeta3
      positive U87MG cells (90-395 nM). (18)F-labeling of the various carbohydrate
      precursors (1a-f) using cryptate-assisted reaction conditions (CH3CN, 85  degrees
      C, 10 min) gave (18)F-labeled glycosyl azides in radiochemical yields (RCYs) of
      up to 84% ([(18)F]2b). The deacetylation and subsequent click reaction with the
      alkyne-bearing cyclic RGD peptide proceeded in one-pot reactions with RCYs as
      high as 81% in 15-20 min at 60  degrees C, using a minimal amount of peptide
      precursor (100 nmol). Optimization of the radiosynthesis strategy gave a decay
      uncorrected RCY of 16-24% after 70-75 min (based on [(18)F]fluoride). Due to
      their high-yield radiosyntheses, the glycopeptides [(18)F]6Glc-RGD and [(18)F]Mlt
      RGD were chosen for comparative biodistribution studies and dynamic small-animal
      PET imaging using U87MG tumor-bearing nude mice. [(18)F]6Glc-RGD and [(18)F]Mlt
      RGD showed significantly decreased liver and kidney uptake by PET relative to the
      2-[(18)F]fluoroglucosyl analog [(18)F]2Glc-RGD, and showed specific tumor uptake
      in vivo. Notably, [(18)F]Mlt-RGD revealed uptake and retention in the U87MG tumor
      comparable to that of [(18)F]Galacto-RGD. Both [(18)F]6Glc-RGD and [(18)F]Mlt-RGD
      were obtained by a reliable and easy click chemistry-based procedure, much more
      rapidly than was [(18)F]Galacto-RGD. Due to its favorable biodistribution and
      tissue clearance in vivo, [(18)F]Mlt-RGD represents a viable alternative
      radiotracer for imaging integrin expression in solid tumors by PET. 

PMID- 24325586
TI  - A tale of two cytokines: IL-17 and IL-22 in asthma and infection.
AB  - The Th17 pathway has recently been shown to play a critical role in host defense,
      allergic responses and autoimmune inflammation. Th17 cells predominantly produce
      IL-17 and IL-22, which are two cytokines with broad effects in the lung and other
      tissues. This review summarizes not only what is currently known about the
      molecular regulation of this pathway and Th17-related cytokine signaling, but
      also the roles of these cytokines in pathogen immunity and asthma. In the last 5
      years, the Th17 field has rapidly grown and research has revealed that the Th17
      pathway is essential in lung pathogenesis in response to exogenous stimuli. As
      work in the field continues, it is expected that many exciting therapeutic
      advances will be made for a broad range of diseases. 

PMID- 24325590
TI  - Commentary on the interactions of HIV and alcohol in the central nervous system.
AB  - This commentary is to highlight the relevance and public interest of the review
      published by Silverstein and Kumar, which focuses on the mechanisms by which
      alcohol and HIV-1 infection cause increased in central nervous system (CNS)
      damage. The overall review is based on previous literature with cell culture
      systems and animal models that have demonstrated that exposure to alcohol and HIV
      infection or HIV viral proteins result in synergistic up-regulation of pro
      inflammatory cytokines and oxidative stress. The authors discuss the effects of
      alcohol on cells in the CNS, followed by a brief discussion on the impact of HIV
      1 and HIV proteins on the CNS, and the final section focuses on the combined
      effects of HIV and alcohol on the CNS as determined by in vitro, in vivo, and
      clinical studies. 

PMID- 24325591
TI  - Comparison of 22-gauge aspiration needle with 22-gauge biopsy needle in
      endoscopic ultrasonography-guided subepithelial tumor sampling.
AB  - OBJECTIVE. Endoscopic ultrasonography (EUS)-guided fine-needle aspiration (EUS
      FNA) may facilitate tissue sampling for histopathological diagnosis of
      subepithelial tumors (SETs) in the gastrointestinal (GI) tract. However,
      immunohistochemistry is not always feasible using EUS-FNA samples due to the low
      quality of specimens often obtained by aspiration. This study aimed to compare
      the use of 22-gauge (G) EUS-guided fine-needle biopsy (EUS-FNB) with 22G EUS-FNA
      for core sampling used for histopathological examination, including
      immunohistochemistry, in patients with GI SETs. METHODS. Twenty-eight patients
      with GI SETs >=2 cm in size were prospectively enrolled at five university
      hospitals in Korea between January and June 2013. They were randomized to undergo
      either EUS-FNB or EUS-FNA. RESULTS. A total of 22 patients was finally analyzed
      in this study: 10 and 12 patients underwent EUS-FNA and EUS-FNB, respectively.
      Compared to the EUS-FNA group, the EUS-FNB group had a significantly lower median
      number of needle passes to obtain macroscopically optimal core samples (4 vs. 2,
      p = 0.025); higher yield rates of macroscopically and histologically optimal core
      samples with three needle passes (30% vs. 92%, p = 0.006; 20% vs. 75%, p = 0.010,
      respectively); and a higher diagnostic sufficiency rate (20% vs. 75%, p = 0.010).
      No technical difficulties were encountered in either group. CONCLUSIONS. This
      study shows that EUS-FNB has a better ability to obtain histological core samples
      and a higher diagnostic sufficiency rate than EUS-FNA and that EUS-FNB is a
      feasible, safe, and preferable modality for adequate core sampling for
      histopathological diagnosis of GI SETs.

PMID- 24325593
TI  - Improving symptom management in hemodialysis patients: identifying barriers and
      future directions.
AB  - BACKGROUND: Hemodialysis (HD) patients experience significant symptom burden that
      is often undertreated. OBJECTIVE: This study identified (1) barriers to symptom
      management in the HD population, (2) potential targets for improving symptom
      burden, (3) provider attitudes toward palliative care for HD patients, and (4)
      perceptions of how transplant eligibility impacts care. DESIGN: Semistructured,
      one-on-one interviews were conducted, audiotaped, and transcribed. Data were
      analyzed qualitatively by two investigators to identify discrete themes.
      SETTING/SUBJECTS: Health care providers (HCPs) and caregivers were recruited
      (June to October 2012) from three outpatient HD units in New York City.
      MEASUREMENTS: Open-ended questions were used with follow-up probes. RESULTS:
      Interviews were completed with 34 HCPs (8 physicians, 2 nurse practitioners, 4
      social workers, 13 registered nurses, 7 patient care technicians) and 20
      caregivers (14 family members, 5 home health aides, 1 friend). Barriers to
      symptom control were identified in three areas: (1) provider unawareness of
      symptoms, (2) provider's uncertainty as to whose responsibility it is to treat
      symptoms, and (3) inherent difficulty in symptom management. Ideas for
      ameliorating symptoms included enhancing systems for patient/caregiver education,
      improving systems for HCP communication with other disciplines, and encouraging
      alternative methods of dialysis when appropriate. HCPs also expressed discomfort
      with the term "palliative care." CONCLUSIONS: Renal HCPs are often unaware of the
      magnitude of symptom burden in their HD patients. This study found that there is
      lack of ownership for assessing and treating these symptoms. Providers also feel
      certain symptoms are "untreatable." Research is needed to develop effective
      treatment strategies for HD populations.

PMID- 24325594
TI  - Effect of constraint-induced therapy on upper limb functions: a randomized
      control trial.
AB  - AIMS: Children with congenital hemiparesis have unilateral upper extremity
      involvement, limiting their ability in unilateral or bilateral manual tasks, thus
      negatively influencing their participation in daily activities. Constraint
      induced movement therapy (CIMT) has been shown to be promising for improving
      upper-limb functions in children with cerebral palsy. Clinical assessments may be
      needed to quantify and qualify changes in children's performance following its
      application. METHODS: This study investigated the effectiveness of a child
      friendly form of CIMT to improve upper extremity functional performance. Thirty
      congenitally hemiparetic children aged 4-8 years were randomly assigned to
      receive either a CIMT program (study group) or a conventional non-structured
      therapy program (control group). The programs were applied for both groups for
      six hours daily, five days weekly for four successive weeks. The Pediatric Arm
      Function Test, Quality of Upper Extremity Skills Test, and isokinetic muscular
      performances of shoulder flexors, extensors, and abductors expressed as peak
      torque were used to evaluate immediate and long-lasting efficacy of CIMT.
      RESULTS: The results showed improvement in the involved upper extremity
      performances in different evaluated tasks immediately post-CIMT program
      application compared with the control group. These improvements continued three
      months later. CONCLUSION: Pediatric CIMT with shaping produced considerable and
      sustained improvement in the involved upper extremity movements and functions in
      children with congenital hemiparesis.

PMID- 24325595
TI  - Inflammatory bowel disease professionals' attitudes to and experiences of
      complementary and alternative medicine.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) use in patients with IBD
      is on the increase. Patients report they use CAM when their condition is
      unresponsive to conventional medication or when they suffer from side-effects,
      negative stress and disease-related concerns. CAM use may improve patients' well
      being but it can also lead to side-effects and interactions with conventional
      medications. Research on attitudes to and experiences of CAM among healthcare
      professionals working with IBD patients is not well studied. Studies in this area
      could lead to enhanced awareness of and improved communication about CAM between
      care staff and IBD patients. The aim of this study was to explore IBD
      professionals' attitudes to and experience of CAM. METHODS: Sixteen physicians
      and nurses, 26-70 years old, who had worked with IBD patients for 1-42 years,
      were recruited. Semi-structured qualitative interviews were conducted.
      Qualitative content analysis was performed. RESULTS: Participants stated patients
      used CAM to improve their well-being generally and there conditions specifically.
      Participants had a positive attitude towards CAM and respected their patients'
      decision to use it, but reported a lack of CAM knowledge. They required education
      about CAM to be able to meet patients' needs and provide adequate information.
      The result of this study indicates that there is a need for CAM education to be
      implemented in nursing and medical school. CONCLUSIONS: All participants had
      experience of IBD patients who had used CAM in an attempt to achieve improvement
      and well-being. Attitudes to CAM were mainly positive, although a problematic
      aspect was lack of knowledge and evidence in relation to CAM. Implementing CAM
      education in nursing and medical school will allow healthcare professionals to
      gain an understanding of therapies widely used by patients with IBD. In clinical
      practice, using a standard questionnaire regarding CAM use allow healthcare
      professionals to better understand their patients' wishes and current CAM use.

PMID- 24325596
TI  - No association between type 1 diabetes and genetic variation in vitamin D
      metabolism genes: a Danish study.
AB  - BACKGROUND: Vitamin D, certain single nucleotide polymorphisms (SNPs) in the
      vitamin D-receptor (VDR) gene and vitamin D metabolism genes have been associated
      with type 1 diabetes (T1D). OBJECTIVE: We wanted to examine if the most widely
      studied SNPs in genes important for production, transport, and action of vitamin
      D were associated with T1D or to circulating levels of vitamin D 25
      hydroxyvitamin D [25(OH)D] in a juvenile Danish population. METHODS: We genotyped
      eight SNPs in five vitamin D metabolism genes in 1467 trios. 25(OH)D status were
      analyzed in 1803 children (907 patients and 896 siblings). RESULTS: We did not
      demonstrate association with T1D for SNPs in the following genes: CYP27B1, VDR,
      GC, CYP2R1, DHCR7, and CYP24A1. Though, variants in the GC gene were
      significantly associated with 25(OH)D levels in the joint model. CONCLUSION: Some
      of the most examined SNPs in vitamin D metabolism genes were not confirmed to be
      associated with T1D, though 25(OH) levels were associated with variants in the GC
      gene.

PMID- 24325597
TI  - Chimeric hERG channels containing a tetramerization domain are functional and
      stable.
AB  - Biochemical and detailed structural information of human ether-a-go-go-related
      gene (hERG) potassium channels are scarce but are a prerequisite to understand
      the unwanted interactions of hERG with drugs and the effect of mutations that
      lead to long QT syndrome. Despite the huge interest in hERG, to our knowledge,
      procedures that provide a purified, functional, and tetrameric hERG channel are
      not available. Here, we describe hybrid hERG molecules, termed chimeric hERG
      channels, in which the N-terminal Per-Arnt-Sim (PAS) domain is deleted and the C
      terminal C-linker as well as the cyclic nucleotide binding domain (CNBD) portion
      is replaced by an artificial tetramerization domain. These chimeric hERG channels
      can be overexpressed in HEK cells, solubilized in detergent, and purified as
      tetramers. When expressed in Xenopus laevis oocytes, the chimeric channels
      exhibit efficient trafficking to the cell surface, whereas a hERG construct
      lacking the PAS and C-linker/CNBD domains is retained in the cytoplasm. The
      chimeric hERG channels retain essential hERG functions such as voltage-dependent
      gating and inhibition by astemizole and the scorpion toxin BeKm-1. The chimeric
      channels are thus powerful tools for helping to understand the contribution of
      the cytoplasmic hERG domains to the gating process and are suitable for in vitro
      biochemical and structural studies. 

PMID- 24325598
TI  - Effect of insertion torque on titanium implant osseointegration: an animal
      experimental study.
AB  - OBJECTIVE: To evaluate the effect of implant insertion torque on the peri-implant
      bone healing and implant osseointegration. MATERIAL AND METHODS: Bilaterally in
      the tibia of five adult New Zealand white rabbits, 20 implants were installed,
      subdivided into four groups, corresponding to two insertion torque conditions
      (low, < 10 Ncm vs. high > 50 Ncm) and 2 experimental periods (2 weeks vs. 4 weeks
      of healing). The implant insertion torque was determined by the surgical drill
      diameter relative to the implant diameter. Implant osseointegration was evaluated
      by quantitative histology (bone-to-implant contact with host bone [BIC-host],
      with neoformed bone [BIC-de novo], with both bone types [BIC-total], and peri
      implant bone [BA/TA]). Every response was modelled over time using GEE (general
      estimation equation) with an unstructured variance-covariance matrix to correct
      for dependency between the measurements from one animal. The statistical
      significance level of alpha = 0.05 was applied. RESULTS: Significantly, more BIC
      host and BIC-total were recorded for H implants compared with L implants after 2
      week of healing (P = 0.010 and P = 0.0001, respectively). However, this result
      was no longer found for the extended healing period. Furthermore, BIC-total
      significantly increased over time for L implants (P < 0.00001). In contrast, the
      significant increase in BA/TA over time was found for H implants (P < 0.01).
      Finally, H insertion torque led to an increased BA/TA after 4 week of healing (P
      < 0.02) compared with the L insertion protocol. CONCLUSION: L insertion torque
      implants installed in the rabbit tibial bone osseointegrate with considerable de
      novo bone formation. This bone neoformation enables L implants to catch up,
      already during the early osseointegration stage, the initial inferior amount BIC
      contact compared with that of H implants. A negative impact of the created strain
      environment accompanying H insertion torque implant installation on the
      biological process of osseointegration could not be observed, at least not at
      tissue level.

PMID- 24325599
TI  - Alcohol and tobacco use among maltreated and non-maltreated adolescents in a
      birth cohort.
AB  - AIMS: This study examines whether child maltreatment experience predicts
      adolescent tobacco and alcohol use. METHODS: The subjects were participants in
      the Mater-University Study of Pregnancy (MUSP), a birth cohort of 7223, of whom
      5158 (71.4%) were available for analysis at the 14-year follow-up. Child
      protection history was obtained from the state's child protection agency and
      confidentially linked. Exposure to reported child maltreatment was the primary
      predictor variable. The outcome variables were self-reported smoking and alcohol
      use. Associations were adjusted for potential confounders. RESULTS: Reported
      child maltreatment was associated with early adolescent smoking [odds ratio (OR)
      1.76, 95% confidence interval (CI) = 1.32-2.34] after adjustment for socio
      demographic variables and coexisting alcohol use. Both neglect/emotional abuse
      (OR 2.03, 95% CI = 1.20-3.42) and neglect/emotional abuse that included physical
      abuse (OR 1.85, 95% CI = 1.19-2.88) were associated with smoking after full
      adjustment, including for coexisting alcohol use. After full adjustment,
      including coexisting smoking, only child neglect/emotional abuse predicted early
      adolescent alcohol use (OR 1.78, 95% CI = 1.06-2.97), but not the other types of
      maltreatment. CONCLUSIONS: Reported child maltreatment predicts early adolescent
      smoking after adjusting for alcohol use, but does not predict alcohol use after
      adjustment for smoking. Both smoking and alcohol use are predicted by reported
      child neglect. Early adolescent smoking is also predicted by multi-type
      maltreatment that includes physical abuse.

PMID- 24325601
TI  - Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine
      specific demethylases display high anticancer activities.
AB  - In prostate cancer, two different types of histone lysine demethylases (KDM),
      LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen
      receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1
      6 by coupling the skeleton of tranylcypromine 7, a known LSD1 inhibitor, with 4
      carboxy-4'-carbomethoxy-2,2'-bipyridine 8 or 5-carboxy-8-hydroxyquinoline 9, two
      2-oxoglutarate competitive templates developed for JmjC inhibition. Hybrid
      compounds 1-6 are able to simultaneously target both KDM families and have been
      validated as potential antitumor agents in cells. Among them, 2 and 3 increase
      H3K4 and H3K9 methylation levels in cells and cause growth arrest and substantial
      apoptosis in LNCaP prostate and HCT116 colon cancer cells. When tested in
      noncancer mesenchymal progenitor (MePR) cells, 2 and 3 induced little and no
      apoptosis, respectively, thus showing cancer-selective inhibiting action. 

PMID- 24325600
TI  - 2-O, 3-O-desulfated heparin inhibits neutrophil elastase-induced HMGB-1 secretion
      and airway inflammation.
AB  - Neutrophil elastase (NE) is a major inflammatory mediator in cystic fibrosis (CF)
      that is a robust predictor of lung disease progression. NE directly causes airway
      injury via protease activity, and propagates persistent neutrophilic inflammation
      by up-regulation of neutrophil chemokine expression. Despite its key role in the
      pathogenesis of CF lung disease, there are currently no effective antiprotease
      therapies available to patients with CF. Although heparin is an effective
      antiprotease and anti-inflammatory agent, its anticoagulant activity prohibits
      its use in CF, due to risk of pulmonary hemorrhage. In this report, we
      demonstrate the efficacy of a 2-O, 3-O-desulfated heparin (ODSH), a modified
      heparin with minimal anticoagulant activity, to inhibit NE activity and to block
      NE-induced airway inflammation. Using an established murine model of
      intratracheal NE-induced airway inflammation, we tested the efficacy of
      intratracheal ODSH to block NE-generated neutrophil chemoattractants and NE
      triggered airway neutrophilic inflammation. ODSH inhibited NE-induced
      keratinocyte-derived chemoattractant and high-mobility group box 1 release in
      bronchoalveolar lavage. ODSH also blocked NE-stimulated high-mobility group box 1
      release from murine macrophages in vitro, and inhibited NE activity in functional
      assays consistent with prior reports of antiprotease activity. In summary, this
      report suggests that ODSH is a promising antiprotease and anti-inflammatory agent
      that may be useful as an airway therapy in CF. 

PMID- 24325602
TI  - Association of oestrogen-containing contraceptives with pulmonary
      lymphangioleiomyomatosis in women with tuberous sclerosis complex--findings from
      a survey.
AB  - OBJECTIVES About 30-40% of women with tuberous sclerosis complex (TSC) develop
      pulmonary lymphangioleiomyomatosis (LAM). Oestrogen seems to be involved in LAM
      pathogenesis and oestrogen-containing contraception should be avoided in women
      with known LAM. However, there is very little data on the use of contraceptives
      in TSC patients. METHODS We conducted a survey on the use of contraception and
      disease characteristics. The questionnaire was forwarded to all adult female TSC
      patients listed in the database of a German patient organisation. RESULTS Data
      from 39 such patients could be analysed. Of these, 15 were diagnosed with LAM.
      Twenty-five patients (65%) confirmed current or past use of oestrogen-containing
      contraceptives. We found a suggestive correlation between the history of
      oestrogen-containing contraception, and LAM (Odds ratio: 6.500; 95% confidence
      interval: 1.199-35.230). However, oestrogen use was not associated with LAM
      complications. CONCLUSIONS Based on our findings, oestrogen-containing
      contraceptives should be resorted to by these patients only with great caution,
      and avoided whenever possible.

PMID- 24325603
TI  - Comparison of binding characterization of two antiviral drugs to human serum
      albumin.
AB  - Ribavirin and lamivudine are representatives of antiviral drugs that are widely
      used to treat viral infections, especially chronic liver disease. To compare
      binding mechanism and behavior of antiviral drugs with human serum albumin (HSA),
      we performed fluorescence spectroscopy and X-ray crystallography to investigate
      the interactions of ribavirin and lamivudine with HSA. Fluorescence spectroscopy
      showed ribavirin and lamivudine inhibit binding affinity each other. Our results
      further demonstrated that ribavirin and lamivdudine interaction with HSA could be
      affected by the presence of other compounds, including the non-steroidal anti
      inflammatory drugs, indometacin. X-ray structures revealed that ribavirin and
      lamivudine bind in IIA subdomain of HSA mainly by forming hydrogen bond and
      hydrophobic interactions forces. The carboxamido of ribavirin forms hydrogen
      bonds with Arg222; Hydroxyl group (6) of ribavirin forms hydrogen bond with
      Arg257. Hydroxyl group (15) of lamivudine forms hydrogen bond with Arg222; amino
      group (4) of lamivudine forms hydrogen bond with carbonyl of Arg257. Our results
      reveal the key biochemical and structural characteristics of the HSA interaction
      with ribavirin and lamivudine, providing guidance for future development of
      ribavirin- and lamivudine-based compounds and a drug-HSA delivery system. 

PMID- 24325604
TI  - Aqueous flare and inflammatory factors in macular edema with central retinal vein
      occlusion: a case series.
AB  - BACKGROUND: The association of inflammatory factors and the aqueous flare value
      with macular edema in central retinal vein occlusion (CRVO) patients remains
      unclear. We investigated the relations between the aqueous flare value and
      vitreous levels of vascular endothelial growth factor (VEGF), soluble
      intercellular adhesion molecule-1 (sICAM-1), and interleukin-6 (IL-6) in patients
      with CRVO and macular edema or patients with idiopathic macular hole (MH).
      METHODS: In 38 patients who underwent unilateral vitrectomy (21 CRVO patients and
      17 MH patients), vitreous samples were obtained during vitrectomy to measure
      VEGF, sICAM-1, and IL-6. Retinal ischemia was evaluated from capillary non
      perfusion on fluorescein angiography, and the CRVO patients were classified into
      nonischemic or ischemic groups. Aqueous flare values were measured with a laser
      flare meter and macular edema was examined by optical coherence tomography.
      RESULTS: The median aqueous flare value increased significantly across the three
      groups (MH group < nonischemic CRVO group < ischemic CRVO group). There was a
      significant correlation between the flare value and vitreous levels of VEGF,
      sICAM-1, and IL-6 in the CRVO group. The flare value was also significantly
      correlated with the severity of macular edema in the CRVO group. CONCLUSIONS:
      Inflammation and/or ischemia may increase vascular permeability and disrupt the
      blood-aqueous barrier by increasing levels of inflammatory factors in patients
      with CRVO and macular edema.

PMID- 24325605
TI  - Enhanced lifetime of excitons in nonepitaxial Au/CdS core/shell nanocrystals.
AB  - The ability of metal nanoparticles to capture light through plasmon excitations
      offers an opportunity for enhancing the optical absorption of plasmon-coupled
      semiconductor materials via energy transfer. This process, however, requires that
      the semiconductor component is electrically insulated to prevent a "backward"
      charge flow into metal and interfacial states, which causes a premature
      dissociation of excitons. Here we demonstrate that such an energy exchange can be
      achieved on the nanoscale by using nonepitaxial Au/CdS core/shell nanocomposites.
      These materials are fabricated via a multistep cation exchange reaction, which
      decouples metal and semiconductor phases leading to fewer interfacial defects.
      Ultrafast transient absorption measurements confirm that the lifetime of excitons
      in the CdS shell (tau ~ 300 ps) is much longer than lifetimes of excitons in
      conventional, reduction-grown Au/CdS heteronanostructures. As a result, the
      energy of metal nanoparticles can be efficiently utilized by the semiconductor
      component without undergoing significant nonradiative energy losses, an important
      property for catalytic or photovoltaic applications. The reduced rate of exciton
      dissociation in the CdS domain of Au/CdS nanocomposites was attributed to the
      nonepitaxial nature of Au/CdS interfaces associated with low defect density and a
      high potential barrier of the interstitial phase. 

PMID- 24325606
TI  - Phylogeography of influenza A H5N1 clade 2.2.1.1 in Egypt.
AB  - BACKGROUND: Influenza A H5N1 has killed millions of birds and raises serious
      public health concern because of its potential to spread to humans and cause a
      global pandemic. While the early focus was in Asia, recent evidence suggests that
      Egypt is a new epicenter for the disease. This includes characterization of a
      variant clade 2.2.1.1, which has been found almost exclusively in Egypt.We
      analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains
      in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling
      of virus dispersion between Egyptian governorates including the most likely
      origin. RESULTS: Phylogeography models of hemagglutinin (HA) and neuraminidase
      (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is
      weak based on Kullback-Leibler values of 0.09 for HA and 0.01 for NA. Association
      Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05),
      indicating that dispersion of H5N1 in Egypt was geographically structured. In
      addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes
      had the strongest statistical support. CONCLUSION: We found that the majority of
      routes with strong statistical support were in the heavily populated Delta
      region. In particular, the Al Qalyubiyah governorate appears to represent a
      popular location for virus transition as it represented a large portion of
      branches in both trees. However, there remains uncertainty about virus dispersion
      to and from this location and thus more research needs to be conducted in order
      to examine this.Phylogeography can highlight the drivers of H5N1 emergence and
      spread. This knowledge can be used to target public health efforts to reduce
      morbidity and mortality. For Egypt, future work should focus on using data about
      vaccination and live bird markets in phylogeography models to study their impact
      on H5N1 diffusion within the country.

PMID- 24325607
TI  - Assessment of liver fibrosis with elastography point quantification technique in
      chronic hepatitis B virus patients: a comparison with liver pathological results.
AB  - BACKGROUND AND AIM: Elastography point quantification (ElastPQ) was a newly non
      invasive method for the assessment of liver fibrosis by measuring liver
      stiffness. We aimed at evaluating the reproducibility of ElastPQ technology in
      the determination of liver stiffness and to investigate the value of ElastPQ in
      liver fibrosis staging among chronic hepatitis B patients. METHODS: A total of
      291 successive patients who underwent liver partial hepatectomy or biopsy were
      examined with the ElastPQ technology for the measurement of liver stiffness. Ten
      ElastPQ measurements were obtained in the right lobe of the liver through the
      seventh to the tenth intercostal space for every patient. The reproducibility of
      ElastPQ technology was analyzed with intraclass correlation (ICC) of reliability
      analysis. Comparing the median of 10 measurements of ElastPQ with liver fibrosis,
      necroinflammatory activity, and steatosis pathologically, as well as gender and
      age, potential factors affecting liver stiffness were explored by multiple linear
      regression analysis, and the performances of ElastPQ were evaluated with repeated
      measures anova and receiver operating characteristic (ROC) curve. RESULTS: The
      ICC of 10 measurements of liver stiffness with ElastPQ technique was 0.798, which
      indicated a good reproducibility. Liver fibrosis and necroinflammatory activity
      were positively correlated with ElastPQ (P = 0.00, 0.01 < 0.05) while other
      factors had no effect on ElastPQ. There was significant difference of ElastPQ
      between S1 (5.60 +/- 2.55 kPa) and S2 (7.44 +/- 3.43 kPa) (P = 0.01 < 0.05), and
      S3 (8.71 +/- 3.14 kPa) and S4 (10.87 +/- 5.25 kPa) (P = 0.01 < 0.05). The area
      under the ROC curve was 0.94 (6.99 kPa, the optimal cut-off value) for ElastPQ
      measured with ElastPQ between S0-1 and S2-3, 0.89 (9.00 kPa) for ElastPQ between
      S2-3 and S4. CONCLUSION: ElastPQ is a valid and reproducible non-invasive
      technology in liver stiffness measurement among chronic hepatitis B patients. The
      stage of liver fibrosis and the grade of necroinflammatory activity are
      associated with values of ElastPQ while liver fibrosis is the dominating factor
      affecting liver stiffness measured by ElastPQ.

PMID- 24325608
TI  - Nanoparticles in orthodontics, a review of antimicrobial and anti-caries
      applications.
AB  - Nanoparticles (NPs) are insoluble particles smaller than 100 nm in size. In order
      to prevent microbial adhesion or enamel demineralization in orthodontic therapy,
      two broad strategies have been used. These are incorporating certain NPs into
      orthodontic adhesives/cements or acrylic resins (nanofillers, silver, TiO2, SiO2,
      hydroxyapatite, fluorapatite, fluorohydroxyapatite) and coating surfaces of
      orthodontic appliances with NPs (i.e. coating bracket surfaces with a thin film
      of nitrogen-doped TiO2). Although the use of NPs in orthodontics can offer new
      possibilities, previous studies investigated the antimicrobial or physical
      characteristic over a short time span, i.e. 24 hours to a few weeks, and the
      limitations of in vitro studies should be recognized. Information on the long
      term performance of orthodontic material using nanotechnology is lacking and
      necessitates further investigation and so do possible safety issues (toxicity),
      which can be related to the NP sizes.

PMID- 24325609
TI  - Visit-to-visit blood pressure variability and cardiovascular death in the
      Systolic Hypertension in the Elderly Program.
AB  - Most studies of an association of visit-to-visit variability of blood pressure
      with increased risk of future adverse cardiovascular events are of short duration
      and rarely include a placebo group. Using data from the double-blind, placebo
      controlled Systolic Hypertension in the Elderly Program, the authors examined
      mortality from cardiovascular causes up to 17 years of follow-up using the
      National Death Index. Visit-to-visit blood pressure variability was associated
      with cardiovascular death after adjustment for sex, age, serum creatinine,
      diabetes, body mass index, smoking status, left ventricular failure, and high
      density lipoprotein cholesterol. The relationship was significantly stronger in
      the active treatment group compared with the placebo group. Although this could
      be the result of an effect of the medications used unrelated to visit-to-visit
      variability, the data are compatible with the hypothesis that inconsistent
      adherence leading to missing active medication doses may be an additional
      explanation for the relationship of visit-to-visit variability with
      cardiovascular death. 

PMID- 24325610
TI  - Microenvironment influence on human colon adenocarcinoma phenotypes and matrix
      metalloproteinase-2, p53 and beta-catenin tumor expressions from identical
      monoclonal cell tumor in the orthotopic model in athymic nude rats.
AB  - The present study aims to identify differences between left and right colon
      adenocarcinoma arising from identical clonal cell and to find out if
      microenvironment has any influence on matrix metalloproteinase-2 (MMP2), p53 and
      beta-catenin tumor expressions. MATERIAL AND METHODS. Rats (RNU) were submitted
      to cecostomy to obtain the orthotopic model of right colon tumor (n = 10), while
      for the left colon model (n = 10), a colon diversion and distal mucous fistula in
      the descending colon was used. Cultivated human colon adenocarcinoma cells (WiDr)
      were inoculated in stomas submucosa. Histopathological analysis, real-time
      reverse transcription-PCR for beta-catenin, p53 and MMP2, as well as
      immunohistochemical analysis for p53 and beta-catenin expression were conducted.
      Central tendency, variance analysis and the Livak delta-delta-CT method were used
      for statistical analysis, adopting a 5% significance level. RESULTS. All tumors
      from the left colon exhibited infiltrative ulceration, while in the right colon
      tumor growth was predominantly exophytic (67%). In the left colon, tumor growth
      was undifferentiated (100%), while it was moderately differentiated in the right
      colon (83%). In right colon tumors, MMP2, p53, and beta-catenin gene expressions
      were higher than compared to left colon (p = 4.59354E-05, p = 0.0035179, p =
      0.00093798, respectively, for MMP2, p53 and beta-catenin). beta-catenin and p53
      results obtained by real-time polymerase chain reaction were confirmed by
      immunohistochemistry assay (p = 0.01 and p = 0.001, respectively, for beta
      catenin and p53). CONCLUSION. Left and right human colon adenocarcinomas
      developed in animal models have distinct phenotypes even when they have the same
      clonal origin. Microenvironment has influenced p53, beta-catenin, and MMP2
      expression in animal models of colon cancer.

PMID- 24325612
TI  - Why more is not always better: new Pap smear guidelines.

PMID- 24325611
TI  - Psychometric properties of the World Health Organization Quality Of Life
      Assessment-Brief in methadone patients: a validation study in northern Taiwan.
AB  - BACKGROUND: Quality of life (QOL) is an important outcome measure in the
      treatment of heroin addiction. The Taiwan version of the World Health
      Organization Quality of Life assessment (WHOQOL-BREF [TW]) has been developed and
      studied in various groups, but not specifically in a population of injection drug
      users. The aim of this study was to analyze the psychometric properties of the
      WHOQOL-BREF (TW) in a sample of injection drug users undergoing methadone
      maintenance treatment. METHODS: A total of 553 participants were interviewed and
      completed the instrument. Item-response distributions, internal consistency,
      corrected item-domain correlation, criterion-related validity, and construct
      validity through confirmatory factor analysis were evaluated. RESULTS: The
      frequency distribution of the 4 domains of the WHOQOL-BREF (TW) showed no floor
      or ceiling effects. The instrument demonstrated adequate internal consistency
      (Cronbach's alpha coefficients were higher than 0.7 across the 4 domains) and all
      items had acceptable correlation with the corresponding domain scores (r = 0.32
      0.73). Correlations (p < 0.01) of the 4 domains with the 2 benchmark items
      assessing overall QOL and general health were supportive of criterion-related
      validity. Confirmatory factor analysis yielded marginal goodness-of-fit between
      the 4-domain model and the sample data. CONCLUSIONS: The hypothesized WHOQOL-BREF
      measurement model was appropriate for the injection drug users after some
      adjustments. Despite different patterns found in the confirmatory factor
      analysis, the findings overall suggest that the WHOQOL-BREF (TW) is a reliable
      and valid measure of QOL among injection drug users and can be utilized in future
      treatment outcome studies. The factor structure provided by the study also helps
      to understand the QOL characteristics of the injection drug users in Taiwan.
      However, more research is needed to examine its test-retest reliability and
      sensitivity to changes due to treatment.

PMID- 24325613
TI  - Mental health: at the root of human development.

PMID- 24325614
TI  - Use of breath-actuated inhalers in patients with asthma and COPD - an advance in
      inhalational therapy: a systematic review.
AB  - The pressurized metered dose inhalers and dry powder inhalers are the most widely
      used devices for inhalation therapy in asthma and chronic obstructive pulmonary
      disease; each of these devices have certain advantages and disadvantages that
      impact their use. Motivation from the virtues of these devices led to the
      development of breath-actuated or breath-activated metered dose inhalers. A
      history of the breath-actuated inhalers, the development and technical aspects,
      studies about the usability, inhalation technique and patient preference, lung
      deposition and impact on lung function are presented in this review article. This
      review presents the use of breath-actuated inhalers in asthma and chronic
      obstructive pulmonary disease and in children and elderly; and a brief economic
      evaluation aims to put the clinical efficacy and ease-of-use of the breath
      actuated inhaler into perspective by understanding the long-term cost benefits
      associated with this device. 

PMID- 24325615
TI  - The synthesis of rigid polycyclic structures for the study of diatropic or steric
      effects of a phenyl ring on CF bond.
AB  - Polycyclic compounds 1a-c were synthesized to study the diatropic effects of a
      flanking phenyl ring on nearby CH and CF bonds. (19)F NMR spectra of 1b and 1c
      were strongly deshielded compared with those of the ring-opened compounds 3b, 7b,
      and 7c. DMol3 calculations on 1a-c provided quantitative bond lengths and
      torsional angles to support the conclusion that the downfield shifts in the (19)F
      NMR spectra are mainly due to steric interactions between the CF bonds and the pi
      clouds of the phenyl ring(s). 

PMID- 24325616
TI  - Septal pacing: still no clarity?

PMID- 24325617
TI  - The freeze on mass media campaigns in England: a natural experiment of the impact
      of tobacco control campaigns on quitting behaviour.
AB  - AIMS: To measure the impact of the suspension of tobacco control mass media
      campaigns in England in April 2010 on measures of smoking cessation behaviour.
      DESIGN: Interrupted time series design using routinely collected population-level
      data. Analysis of use of a range of types of smoking cessation support using
      segmented negative binomial regression. SETTING: England. MEASUREMENTS: Use of
      non-intensive support: monthly calls to the National Health Service (NHS)
      quitline (April 2005-September 2011), text requests for quit support packs
      (December 2007-10) and web hits on the national smoking cessation website
      (January 2009-March 2011). Use of intensive cessation support: quarterly data on
      the number of people setting a quit date and 4-week quitters at the NHS Stop
      Smoking Services (SSS) (quarter 1, 2001 and quarter 3, 2011). FINDINGS: During
      the suspension of tobacco control mass media spending, literature requests fell
      by 98% [95% confidence interval (CI) = 96-99], and quitline calls and web hits
      fell by 65% (95% CI = 43-79) and 34% (95% CI: 11-50), respectively. The number of
      people setting a quit date and 4-week quitters at the SSS increased throughout
      the study period. CONCLUSIONS: The suspension of tobacco control mass media
      campaigns in England in 2012 appeared to markedly reduce the use of smoking
      cessation literature, quitline calls and hits on the national smoking cessation
      website, but did not affect attendance at the Stop Smoking Services. Within a
      comprehensive tobacco control programme, mass media campaigns can play an
      important role in maximizing quitting activity.

PMID- 24325619
TI  - A prehospital use of ITClamp for haemostatic control and fixation of a chest
      tube.
AB  - We here present three cases in which a new device, the ITClamp Hemorrhage Control
      System (Innovative Trauma Care, Inc., Edmonton, Canada), was used for bleeding
      control and for securing a chest tube. 

PMID- 24325618
TI  - Molecular mechanism of apoptosis induction in skin cancer cells by the
      centipedegrass extract.
AB  - BACKGROUND: Centipedegrass extract (CGE) is mainly composed of maysin and its
      derivatives, which are recognized internationally as natural compounds. Compared
      to other flavonoids, maysin has a unique structure in that mannose is bound to
      the flavonoid backbone. CGE exhibits some biological properties in that it can
      function as an anti-oxidant, anti-inflammatory, anti-adipogenic, and
      insecticidal. Whether CGE has other biological functions, such as anti-cancer
      activity, is unknown. METHODS: B16F1 (mouse) and SKMEL-5 (human) cells were
      treated with CGE, and their subsequent survival was determined using MTT assay.
      We performed a cell cycle analysis using propidium iodide (PI), and detected
      apoptosis using double staining with annexin V-FITC/PI. In addition, we examined
      mitochondrial membrane potentials using flow cytometry, as well as signaling
      mechanisms with an immunoblotting analysis. RESULTS: CGE inhibited skin cancer
      cell growth by arresting the cell cycle in the G2/M phase, and increased both
      early and late apoptotic cell populations without affecting normal cells.
      Furthermore, we observed mitochondrial transmembrane depolarization, increased
      cytochrome-c release, caspase-3 and caspase-7 activation, and increased poly ADP
      ribose polymerase degradation. CGE also downregulated activation of p-AKT, p
      glycogen synthase kinase-3beta (GSK-3beta), and p-BAD in a time-dependent manner.
      LY294002 inhibition of phosphoinositide 3-kinase (PI3K) significantly sensitized
      skin cancer cells, which led to an increase in CGE-induced apoptosis.
      CONCLUSIONS: CGE controlled skin cancer cell growth by inhibiting the
      PI3K/AKT/GSK-3beta signaling pathway and activating the effector caspases. This
      study is the first to demonstrate anti-cancer properties for CGE, and that CGE
      may be an effective therapeutic agent for treating skin cancer.

PMID- 24325620
TI  - Ten-year review of gastrointestinal stromal tumours at a tertiary referral
      hospital in New Zealand.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common
      mesenchymal tumours of the gastrointestinal tract and make up 1-2% of all
      gastrointestinal malignancies. Traditionally, the treatment of choice for primary
      disease is surgical resection; however, no single surgeon or institution gets
      extensive exposure to these patients so appropriate decision-making is difficult,
      particularly since the introduction of the tyrosine kinase inhibitor imatinib,
      which has become an important additional management tool. METHOD: All patients
      were diagnosed and treated for GISTs in Christchurch Hospital (Christchurch, New
      Zealand) between 1 January 2000 and 31 December 2010. We maintain a prospective
      database of all patients with GISTs. Data on clinical and histopathological
      variables, management and survival outcomes were recorded. These were then
      reviewed. RESULTS: There were 93 patients in this study. Fifty were women. Median
      age was 69 (interquartile range (IQR) 59-76) years. Fifty-one tumours were
      located in the stomach, 27 in the small bowel, six in the colon, three in the
      oesophagus, one in the rectum and five were extra-gastrointestinal. In total, 22
      patients received imatinib therapy; four patients with metastatic disease had
      imatinib as sole therapy. The median follow-up was 58 (IQR 30-90) months. The 5
      year overall survival and disease-free survival (DFS) for the entire study
      population was 69% and 64%, respectively. The 5-year DFS was higher for all
      patients who have localized disease when compared with those who have metastatic
      disease (76% versus 28%, P-value 0.001). CONCLUSION: Surgery aiming at an R0
      resection remains the mainstay of treatment. We propose the most effective way to
      grow the knowledge base in New Zealand is the establishment of a national
      register, thereby allowing better clinical decision-making by interpretation of a
      larger data set.

PMID- 24325621
TI  - A novel method for volumetric assessment of tooth wear using three-dimensional
      reverse-engineering technology: a preliminary report.
AB  - OBJECTIVE: To describe a newly developed three-dimensional (3D) digital
      superimposition method for quantitative evaluation of tooth wear that occurs
      during orthodontic treatment. MATERIALS AND METHODS: The sample consisted of
      dental casts obtained from 56 patients (23 male patients and 33 female patients;
      mean +/- standard deviation age  =  21.8 +/- 5.1 years) who received orthodontic
      treatment with extraction of four premolars. The maxillary and mandibular dental
      casts taken before (T1) and after (T2) orthodontic treatments were scanned, and
      3D images of the canines were constructed. The canines at T1 were superimposed
      with those at T2 with the best-fit method using the middle third of the labial
      and lingual surface as the reference area. To measure the volume of the canines,
      four boundary planes were constructed, and the differences in volume before and
      after orthodontic treatment were calculated. RESULTS: The mean volume of tooth
      wear of the 224 canines was 2.0 mm(3) after 35.5 months of orthodontic treatment.
      The volume of canine tooth wear was 2.3 +/- 1.5 mm(3) in male subjects and 1.9 +/
      1.2 mm(3) in female subjects. The mean wear of the upper right canines (2.4 +/-
      2.0 mm(3)) was significantly greater than that of the lower right canines (1.9 +/
      2.6 mm(3)). CONCLUSIONS: Regional registration of teeth in 3D digital models is
      useful for quantitative evaluation of tooth wear in orthodontic patients. This
      method may also be used to assess treatment results in restorative dentistry.

PMID- 24325622
TI  - Comparison of transverse analysis between posteroanterior cephalogram and cone
      beam computed tomography.
AB  - OBJECTIVES: To evaluate maxillary and mandibular alveolar and basal bone widths
      using cone-beam computed tomography (CBCT) and to verify the correlation between
      CBCT images and posteroanterior (PA) cephalograms. MATERIALS AND METHODS: The
      CBCT scans and PA cephalograms were obtained from 20 men (age range  =  24.0-29.1
      years; mean age  =  27.2 years; SD  =  2.8 years) and 20 women (age range  = 
      20.3-28.1 years; mean age  =  26.4 years; SD  =  3.2 years) with normal
      occlusion. On CBCT images, maxillary and mandibular bone widths were measured at
      three posterior sites and five bone levels. The differences between maxillary and
      mandibular bone widths were calculated and compared with conventional transverse
      width of PA cephalograms. RESULTS: Statistically significant differences in
      maxillary and mandibular bone widths were detected at different levels and sites.
      Bone widths were significantly increased from the alveolar crest toward the basal
      bone in the maxillary molar and mandibular second premolar and molar areas. A
      statistically significant correlation was only found between CBCT images and PA
      cephalograms for maxillomandibular width at the first molar area. CONCLUSION: The
      results of this study suggested that three-dimensional assessment of
      maxillomandibular width is mandatory for the transverse analysis.

PMID- 24325623
TI  - Orthodontic bonding to porcelain: a systematic review.
AB  - OBJECTIVE: To use a systematic review to determine which materials and
      technique/protocol present the highest success rate in bonding brackets to
      porcelain surfaces. MATERIALS AND METHODS: Different databases were searched
      without limitations up to July 2013. Additionally, the bibliographies of the
      finally selected articles were hand searched to identify any relevant
      publications that were not identified earlier. In vitro and in vivo articles were
      included. RESULTS: No in vivo articles were found that fulfilled the inclusion
      criteria. A total of 45 in vitro articles met all inclusion criteria. They were
      published between 2000 to July 2013. CONCLUSIONS: The best protocol described in
      this review is the etching of 9.6% hydrofluoric acid for 1 minute, rinsed for 30
      seconds, and then air-dried. The etching of hydrofluoric acid should be followed
      by an application of silane. Considering the harmful effects of etching with
      hydrofluoric acid, another appropriate suggestion is mechanical roughening with
      sandblasting followed by an application of silane.

PMID- 24325624
TI  - Endothelin-1 signalling controls early embryonic heart rate in vitro and in vivo.
AB  - AIM: Spontaneous activity of embryonic cardiomyocytes originates from
      sarcoplasmic reticulum (SR) Ca(2+) release during early cardiogenesis. However,
      the regulation of heart rate during embryonic development is still not clear. The
      aim of this study was to determine how endothelin-1 (ET-1) affects the heart rate
      of embryonic mice, as well as the pathway through which it exerts its effects.
      METHODS: The effects of ET-1 and ET-1 receptor inhibition on cardiac contraction
      were studied using confocal Ca(2+) imaging of isolated mouse embryonic
      ventricular cardiomyocytes and ultrasonographic examination of embryonic cardiac
      contractions in utero. In addition, the amount of ET-1 peptide and ET receptor a
      (ETa) and b (ETb) mRNA levels were measured during different stages of
      development of the cardiac muscle. RESULTS: High ET-1 concentration and
      expression of both ETa and ETb receptors was observed in early cardiac tissue. ET
      1 was found to increase the frequency of spontaneous Ca(2+) oscillations in E10.5
      embryonic cardiomyocytes in vitro. Non-specific inhibition of ET receptors with
      tezosentan caused arrhythmia and bradycardia in isolated embryonic cardiomyocytes
      and in whole embryonic hearts both in vitro (E10.5) and in utero (E12.5). ET-1
      mediated stimulation of early heart rate was found to occur via ETb receptors and
      subsequent inositol trisphosphate receptor activation and increased SR Ca(2+)
      leak. CONCLUSION: Endothelin-1 is required to maintain a sufficient heart rate,
      as well as to prevent arrhythmia during early development of the mouse heart.
      This is achieved through ETb receptor, which stimulates Ca(2+) leak through IP3
      receptors.

PMID- 24325625
TI  - Structural insights into substrate recognition by the Neurospora Varkud satellite
      ribozyme: importance of U-turns at the kissing-loop junction.
AB  - Substrate recognition by the Neurospora Varkud satellite ribozyme depends on the
      formation of a magnesium-dependent kissing-loop interaction between the stem-loop
      I (SLI) substrate and stem-loop V (SLV) of the catalytic domain. From mutagenesis
      studies, it has been established that this I/V kissing-loop interaction involves
      three Watson-Crick base pairs and is associated with a structural rearrangement
      of the SLI substrate that facilitates catalysis. Here, we report the NMR
      structural characterization of this I/V kissing-loop using isolated stem-loops.
      NMR studies were performed on different SLI/SLV complexes containing a common SLV
      and shiftable, preshifted, or double-stranded SLI variants. These studies confirm
      the presence of three Watson-Crick base pairs at the kissing-loop junction and
      provide evidence for the structural rearrangement of shiftable SLI variants upon
      SLV binding. NMR structure determination of an SLI/SLV complex demonstrates that
      both the SLI and SLV loops adopt U-turn structures, which facilitates
      intermolecular Watson-Crick base pairing. Several other interactions at the I/V
      interface, including base triples and base stacking, help create a continuously
      stacked structure. These NMR studies provide a structural basis to understand the
      stability of the I/V kissing-loop interaction and lead us to propose a kinetic
      model for substrate activation in the VS ribozyme. 

PMID- 24325626
TI  - In young patients with Turner or Down syndrome, Graves' disease presentation is
      often preceded by Hashimoto's thyroiditis.
AB  - BACKGROUND: It is known that, in the general population, there exists a continuum
      between Hashimoto's thyroiditis (HT) and Graves' disease (GD) within the spectrum
      of autoimmune thyroid diseases, although the mechanisms involved in the
      metamorphosis from HT to GD or vice versa have not been elucidated as of yet. The
      aim of this study was to ascertain whether the association with Down or Turner
      syndromes (DS and TS) may affect the switching process from HT to GD. METHODS:
      Thirty-five young GD patients with either DS or TS (group A) and 109 age-matched
      GD patients with neither DS nor TS were retrospectively investigated in order to
      either confirm or exclude antecedents of HT. The investigations were based on
      either clinical records or questionnaires addressed to family pediatricians.
      Retrospective investigations also aimed to ascertain how many patients in each
      group exhibited a biochemical picture of either subclinical or overt
      hypothyroidism at the time of HT diagnosis, and how many had received
      levothyroxine (L-T4) therapy prior to the onset of GD. In both groups, all the
      patients with documented antecedents of HT underwent an assessment of their
      iodine status after GD diagnosis. RESULTS: Antecedents of HT were significantly
      more common in group A than in group B (25.7% vs. 3.7%, p=0.0004), with a time
      interval between HT and GD that was significantly higher in group A (p=0.003).
      Both thyroid function and autoimmunity tests at HT presentation and the
      prevalence of patients who underwent L-T4 therapy prior to GD diagnosis were not
      significantly different in the two groups, nor was the iodine status after GD
      diagnosis. CONCLUSIONS: In young patients with TS or DS, GD presentation is often
      (25.7% of cases) preceded by HT. This evolution trend does not seem to be
      conditioned by either thyroid tests at HT diagnosis, or L-T4 treatment, or iodine
      status alterations. Patients with these chromosomopathies and coexisting HT may
      be at high risk of progressing to GD. The pathophysiological bases of these
      findings need to be clarified.

PMID- 24325627
TI  - Regeneration of spermatogenesis in a mouse model of azoospermia by follicle
      stimulating hormone and oestradiol.
AB  - Busulfan is a chemotherapeutic drug that induces sterility, azoospermia and
      testicular atrophy. To induce degeneration of spermatogenesis, we used different
      amounts of busulfan. Adult male C57Bl/6 mice were treated with 15, 30 and 45 mg
      kg(-1) of busulfan. After 5 weeks, animals had daily injections of 7.5 IU human
      follicle-stimulating hormone (hFSH) and 12.5 MUg kg(-1) oestradiol benzoate (EB),
      separately or simultaneously. After this time, the animals were killed and blood
      samples were taken through cardiac puncture. Testes were used for histopathology
      experiments, DNA flow cytometry and RNA extraction for expression of c-kit and
      cyclin B1 genes. EB unlike FSH has induced stimulatory effects on
      spermatogenesis, increased the level of serum testosterone 2-fold and caused a 2
      fold increase in the number of haploid cells. The result showed that hFSH with EB
      multiplied EB stimulatory effects on spermatogenesis up to four times. Expression
      of c-kit and cyclin B1 genes increased in EB and hFSH+EB groups. These findings
      suggest that EB regulates spermatogonial stem cells via hFSH. hFSH with EB had
      synergistic effect on regeneration of spermatogenesis. 

PMID- 24325628
TI  - Lower extremity dexterity is associated with agility in adolescent soccer
      athletes.
AB  - Agility is important for sport performance and potentially injury risk; however,
      factors affecting this motor skill remain unclear. Here, we evaluated the extent
      to which lower extremity dexterity (LED) and muscle performance were associated
      with agility. Fourteen male and 14 female soccer athletes participated. Agility
      was evaluated using a hopping sequence separately with both limbs and with the
      dominant limb only. The LED test evaluated the athletes' ability to dynamically
      regulate foot-ground interactions by compressing a spring prone to buckling with
      the lower limb. Muscle performance included hip and knee isometric strength and
      vertical jump height. Correlation analyses were used to assess the associations
      between muscle performance, LED, and agility. Multiple regression models were
      used to determine whether linear associations differed between sexes. On average,
      the female athletes took longer to complete the agility tasks than the male
      athletes. This difference could not be explained by muscle performance.
      Conversely, LED was found to be the primary determinant of agility (double limb:
      R(2) = 0.61, P < 0.001; single limb: R(2) = 0.63, P < 0.001). Our findings
      suggest that the sensorimotor ability to dynamically regulate foot-ground
      interactions as assessed by the LED test is predictive of agility in soccer
      athletes. We propose that LED may have implications for sport performance, injury
      risk, and rehabilitation.

PMID- 24325629
TI  - Factors associated with pretreatment and treatment dropouts: comparisons between
      Aboriginal and non-Aboriginal clients admitted to medical withdrawal management.
AB  - BACKGROUND: Addiction treatment faces high pretreatment and treatment dropout
      rates, especially among Aboriginals. In this study we examined characteristic
      differences between Aboriginal and non-Aboriginal clients accessing an inpatient
      medical withdrawal management program, and identified risk factors associated
      with the probabilities of pretreatment and treatment dropouts, respectively.
      METHODS: 2231 unique clients (Aboriginal = 451; 20%) referred to Vancouver Detox
      over a two-year period were assessed. For both Aboriginal and non-Aboriginal
      groups, multivariate logistic regression analyses were conducted with
      pretreatment dropout and treatment dropout as dependent variables, respectively.
      RESULTS: Aboriginal clients had higher pretreatment and treatment dropout rates
      compared to non-Aboriginal clients (41.0% vs. 32.7% and 25.9% vs. 20.0%,
      respectively). For Aboriginal people, no fixed address (NFA) was the only
      predictor of pretreatment dropout. For treatment dropout, significant predictors
      were: being female, having HCV infection, and being discharged on welfare check
      issue days or weekends. For non-Aboriginal clients, being male, NFA, alcohol as a
      preferred substance, and being on methadone maintenance treatment (MMT) at
      referral were associated with pretreatment dropout. Significant risk factors for
      treatment dropout were: being younger, having a preferred substance other than
      alcohol, having opiates as a preferred substance, and being discharged on
      weekends. CONCLUSIONS: Our results highlight the importance of social factors for
      the Aboriginal population compared to substance-specific factors for the non
      Aboriginal population. These findings should help clinicians and decision-makers
      to recognize the importance of social supports especially housing and initiate
      appropriate services to improve treatment intake and subsequent retention,
      physical and mental health outcomes and the cost-effectiveness of treatment.

PMID- 24325630
TI  - Targeted transferrin-modified polymeric micelles: enhanced efficacy in vitro and
      in vivo in ovarian carcinoma.
AB  - In this study, transferrin (Tf)-modified poly(ethylene glycol)
      phosphatidylethanolamine (mPEG-PE) micelles loaded with the poorly water-soluble
      drug, R547 (a potent and selective ATP-competitive cyclin-dependent kinase (CDK)
      inhibitor), were prepared and evaluated for their targeting efficiency and
      cytotoxicity in vitro and in vivo to A2780 ovarian carcinoma cells, which
      overexpress transferrin receptors (TfR). At 10 mM lipid concentration, both Tf
      modified and plain micelles solubilized 800 MUg of R547. Tf-modified micelles
      showed enhanced interaction with A2780 ovarian carcinoma cells in vitro. The
      involvement of TfR in endocytosis of Tf-modified micelles was confirmed by
      colocalization studies of micelle-treated cells with the endosomal marker Tf
      Alexa488. We confirmed endocytosis of micelles in an intact form with micelles
      loaded with a fluorescent dye and additionally labeled with fluorescent lipid.
      The in vitro cytotoxicity and in vivo tumor growth inhibition studies in A2780
      tumor bearing mice confirmed the enhanced efficacy of Tf-modified R547-loaded
      micelles compared to free drug solution and to nonmodified micelles. The results
      of this study demonstrate the potential application of Tf-conjugated polymeric
      micelles in the treatment of tumors overexpressing TfR. 

PMID- 24325631
TI  - Beneficial effects of dual vascular endothelial growth factor receptor/fibroblast
      growth factor receptor inhibitor brivanib alaninate in cirrhotic portal
      hypertensive rats.
AB  - BACKGROUND AND AIM: Vascular endothelial (VEGF) and fibroblast growth factor
      (FGF)-induced hepatic stellate (HSCs) and liver endothelial cells (LECs)
      activation accelerates hepatic fibrogenesis and angiogenesis, and hemodynamic
      dysarrangements in cirrhosis. VEGF targeting agents had been reported as
      potential drugs for cirrhosis. However, the evaluation of effects of dual
      VEGF/FGF targeting agent in cirrhosis is still limited. METHODS: Using
      hemodynamic parameters, blood chemistry, primary isolated HSCs and LECs,
      histology, and digital imaging, we assess the effects of 2-week brivanib
      alaninate, a dual VEGFR/FGFR inhibitor, treatment in the pathophysiology of bile
      duct-ligated-cirrhotic rats. RESULTS: Fibrogenic and angiogenic markers in the
      serum and liver of bile duct-ligated-cirrhotic rats, including hydroxyproline,
      transforming growth factor-beta1, angiopoietin-1, VEGF, FGF-2, endocan and
      phosphorylated-VEGFR2/VEGFR2, and phosphorylated-FGFR/FGFR together with hepatic
      CD31/angiopoietin-1 expressions (immunohistochemistry staining), angiogenesis
      (micro-computed tomography scan), microcirculatory dysfunction (in vivo
      miscroscopy and in situ liver perfusion study), portal hypertension, and
      hyperdynamic circulations (colored microsphere methods) were markedly suppressed
      and ameliorated by brivanib alaninate treatment. In in vitro study, acute
      brivanib alaninate incubation inhibited the transforming growth factor-beta1
      induced HSCs contraction/migration and VEGF-induced LECs angiogenesis.
      Concomitantly, the overexpression of various fibrogenic and angiogenic markers in
      HSCs and LECs, and in their culture media, was increased in parallel and these
      changes were suppressed by acute brivanib alaninate incubation. CONCLUSIONS: This
      study demonstrated that brivanib alaninate targeting multiple mechanisms and
      working in the different pathogenic steps of the complications of cirrhotic rats
      with portal hypertension.

PMID- 24325633
TI  - Plasma uric acid response to rasburicase: early marker for acute kidney injury in
      tumor lysis syndrome?
AB  - Acute kidney injury (AKI) is associated with high morbidity and mortality in
      tumor lysis syndrome (TLS). The goal of this study was to assess a practical
      approach involving a simple risk-prediction model for AKI in patients at high
      risk for clinical TLS treated according to standardized guidelines. We collected
      data on 62 patients at high risk for clinical TLS. We evaluated whether the
      magnitude of the plasma uric acid decrease in response to rasburicase predicted
      AKI. According to RIFLE criteria (Risk, Injury, Failure, sustained Loss, End
      stage kidney disease), 41 (66.1%) patients had AKI. AKI was associated with
      higher hospital (26.8% vs. 0%, p = 0.01) and 6-month (41.4% vs. 9.5%, p = 0.04)
      mortality. The plasma uric acid decrease after rasburicase was significantly
      larger in patients who did not develop AKI than in those who did (95% vs. 84%; p
      < 0.01). By multivariate analysis, independent determinants of AKI were
      hypertension and a plasma uric acid decrease smaller than 92.9% 6 h after
      rasburicase.

PMID- 24325634
TI  - BCL6 corepressor gene dysregulation due to chromosomal translocation in acute
      myeloid leukemia: a new mechanism based on long non-coding RNA dislocation?

PMID- 24325635
TI  - Berberine radiosensitizes human nasopharyngeal carcinoma by suppressing hypoxia
      inducible factor-1alpha expression.
AB  - CONCLUSION: Berberine confers radiosensitivity on nasopharyngeal carcinoma (NPC)
      and this is associated with the down-regulation of hypoxia-inducible factor
      1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression.
      Berberine could be a promising radiosensitizer for NPC radiotherapy. OBJECTIVES:
      NPC has a poor prognosis. Radiotherapy as first-line therapy significantly
      increases patient survival but radioresistance is a problem. This study aimed to
      investigate the radiosensitizing effects of berberine on NPC and explore the
      underlying mechanisms. METHODS: CNE-1 and CNE-2 cells were exposed to hypoxia and
      treated with berberine at different concentrations. The MTT assay, clonogenic
      assay, and flow cytometry were performed to analyze cell proliferation, colony
      formation, and apoptosis. The expression of HIF-1alpha and VEGF was assessed by
      Western blot and immunofluorescence analysis. Male nude mice inoculated
      subcutaneously with CNE-2 cells were used to examine the sensitizing effects of
      berberine in vivo. RESULTS: Berberine efficiently radiosensitized NPC cells and
      xenografts in mice, and inhibited hypoxia/radiation-induced up-regulation of HIF
      1alpha and VEGF expression.

PMID- 24325636
TI  - Predictive value of middle ear aeration before second-stage operation in staged
      tympanoplasty with soft-wall reconstruction.
AB  - CONCLUSION: The extent of middle ear aeration before second-stage canal wall-down
      (CWD) tympanoplasty was correlated with postoperative middle ear stability.
      OBJECTIVE: To evaluate middle ear aeration before second-stage CWD tympanoplasty
      as a predictor of postoperative re-aeration potential and external auditory canal
      (EAC) stability in staged CWD tympanoplasty with soft-wall reconstruction (SWR).
      METHODS: Middle ear aeration was evaluated before and at 1 year after the second
      stage operation in patients who underwent staged CWD tympanoplasty with SWR for
      middle ear cholesteatoma. Based on the computed tomography (CT) findings, middle
      ear aeration was graded as A when the mastoid and tympanic cavities were aerated,
      B when only the tympanic cavity was aerated, and C in cases with no aeration in
      the tympanic cavity. We also examined postoperative EAC stability. RESULTS: Forty
      one ears were included. In all, 17 of 19 ears (89.5%) with grade A aeration
      preoperatively maintained grade A aeration postoperatively, while 5 of 18 ears
      (27.8%) with grade B aeration had grade A aeration, and no ear with grade C
      aeration had recovered grade A aeration. All ears with grade A aeration
      preoperatively maintained smooth EACs. EAC retraction requiring additional
      treatment occurred in five ears with grade B aeration and all ears with grade C
      aeration.

PMID- 24325637
TI  - Geographical differences in upper abdominal resectional surgery and high-volume
      procedures in Sweden during 2009-2011.
AB  - BACKGROUND: Upper abdominal surgery comprises many different procedures, from
      major resectional surgery on the esophagus, stomach, liver, and pancreas, to high
      volume operations such as cholecystectomy and bariatric surgery. The aim of the
      present study was to evaluate geographical differences, if any, in number of
      procedures performed per capita among the 6 healthcare regions and the 21 Swedish
      counties, responsible for the health care of its inhabitants. METHODS: Data on
      resectional surgery and high-volume procedures were collected for the study
      period (2009-2011) from the Swedish National Patient Register. Annual number of
      procedures and procedures performed per 100,000 inhabitants was registered based
      on the place of residence of patients. RESULTS: In the six healthcare regions,
      the number of resections per 100,000 inhabitants on the esophagus varied from 1.8
      to 3.9, stomach 5.3-6.7, liver 6.7-13.2, and pancreas 4.9-8.3. Corresponding
      figures for cholecystectomies were 146.7-191.3 and for bariatric surgery 33.1
      97.4. The southeast region had the highest incidence of major resectional
      surgery, except for gastric resections. A high number of cholecystectomies were
      performed in all regions. Bariatric surgery was most common in the Stockholm
      region. At county level, the variations were larger, particularly for liver
      surgery and high-volume procedures. CONCLUSION: Significant geographical
      differences were observed between the six healthcare regions and at county level,
      when studying the number of procedures performed per 100,000 inhabitants. We
      believe that this reflects local traditions in selection of patients for
      resectional surgery and differences in capacity for meeting the high demand for
      bariatric surgery.

PMID- 24325638
TI  - Analysis of recent papers in hypertension treatment of hypertension in the
      setting of acute intracerebral hemorrhage: still no clear answer on the best BP
      level to intervene or what BP goal to achieve.

PMID- 24325639
TI  - Can near-peer medical students effectively teach a new curriculum in physical
      examination?
AB  - BACKGROUND: Students in German medical schools frequently complain that the
      subject 'clinical examination' is not taught in a satisfying manner due to time
      constraints and lack of personnel resources. While the effectiveness and
      efficiency of practice-oriented teaching in small groups using near-peer teaching
      has been shown, it is rarely used in German medical schools. We investigated
      whether adding a new near-peer teaching course developed with student input plus
      patient examination under supervision in small groups improves basic clinical
      examination skills in third year medical students compared to a traditional
      clinical examination course alone. METHODS: Third year medical students
      registered for the mandatory curricular clinical examination course at the
      medical faculty of the Technische Universitat Munchen were invited to participate
      in a randomised trial with blinded outcome assessment. Students were randomised
      to the control group participating in the established curricular physical
      examination course or to the intervention group, which received additional near
      peer teaching for the same content. The learning success was verified by a
      voluntary objective structured clinical examination (OSCE). RESULTS: A total of
      84 students were randomised and 53 (63%) participated in the final OSCE. Students
      in the control group scored a median of 57% (25th percentile 47%, 75th percentile
      61%) of the maximum possible total points of the OSCE compared to 77% (73%, 80%;
      p < 0.001) for students in the intervention group. Only two students in the
      intervention group received a lower score than the best student in the control
      group. CONCLUSION: Adding a near-peer teaching course to the routine course
      significantly improved the clinical examination skills of medical students in an
      efficient manner in the context of a resource-constrained setting.

PMID- 24325640
TI  - Canalicular adenoma immunoprofile: a case report.
AB  - OBJECTIVES: To report a case of canalicular adenoma (CA) and discuss the use of
      immunohistochemistry to better address the diagnosis given some unusual
      characteristics in this patient. BACKGROUND: CA is an uncommon benign neoplasm
      that can develop in minor salivary gland duct tissues throughout the oral cavity.
      At histology, it shares several features with other salivary tumors.
      Immunohistochemistry can be useful in the differential diagnosis. MATERIALS AND
      METHODS: The clinical presentation consisted in a nodule on the left upper lip of
      an 85-year-old man. The patient's main complaint was upper denture instability
      secondary to soft tissue changes. The nodule was excised under local anesthesia
      and underwent histological and immunohistochemical examination to rule out any
      malignancy. RESULTS: Histological findings, cytokeratin positivity and the
      absence of any reactivity to specific markers of myoepithelial differentiation
      confirmed the epithelial nature of the lesion. CONCLUSION: The histological
      diagnosis of benign salivary tumors such as CA can be confirmed by
      immunohistochemistry.

PMID- 24325641
TI  - New carbapenases in Brazil.

PMID- 24325642
TI  - Torted pulmonary sequestration masquerading as empyema in a child.

PMID- 24325643
TI  - An engineering commentary on "Interference of avalanche transceivers".

PMID- 24325644
TI  - The glycosyltransferase involved in thurandacin biosynthesis catalyzes both O-
      and S-glycosylation.
AB  - The S-glycosyltransferase SunS is a recently discovered enzyme that selectively
      catalyzes the conjugation of carbohydrates to the cysteine thiol of proteins.
      This study reports the discovery of a second S-glycosyltransferase, ThuS, and
      shows that ThuS catalyzes both S-glycosylation of the thiol of cysteine and O
      glycosylation of the hydroxyl group of serine in peptide substrates. ThuS
      catalyzed S-glycosylation is more efficient than O-glycosylation, and the enzyme
      demonstrates high tolerance with respect to both nucleotide sugars and peptide
      substrates. The biosynthesis of the putative products of the thuS gene cluster
      was reconstituted in vitro, and the resulting S-glycosylated peptides thurandacin
      A and B exhibit highly selective antimicrobial activity toward Bacillus
      thuringiensis. 

PMID- 24325645
TI  - A noncompetitive inhibitor for Mycobacterium tuberculosis's class IIa fructose
      1,6-bisphosphate aldolase.
AB  - Class II fructose 1,6-bisphosphate aldolase (FBA) is an enzyme critical for
      bacterial, fungal, and protozoan glycolysis/gluconeogenesis. Importantly, humans
      lack this type of aldolase, having instead a class I FBA that is structurally and
      mechanistically distinct from class II FBAs. As such, class II FBA is considered
      a putative pharmacological target for the development of novel antibiotics
      against pathogenic bacteria such as Mycobacterium tuberculosis, the causative
      agent for tuberculosis (TB). To date, several competitive class II FBA substrate
      mimic-styled inhibitors have been developed; however, they lack either
      specificity, potency, or properties that limit their potential as possible
      therapeutics. Recently, through the use of enzymatic and structure-based assisted
      screening, we identified 8-hydroxyquinoline carboxylic acid (HCA) that has an
      IC50 of 10 +/- 1 MUM for the class II FBA present in M. tuberculosis (MtFBA). As
      opposed to previous inhibitors, HCA behaves in a noncompetitive manner, shows no
      inhibitory properties toward human and rabbit class I FBAs, and possesses anti-TB
      properties. Furthermore, we were able to determine the crystal structure of HCA
      bound to MtFBA to 2.1 A. HCA also demonstrates inhibitory effects for other class
      II FBAs, including pathogenic bacteria such as methicillin-resistant
      Staphylococcus aureus. With its broad-spectrum potential, unique inhibitory
      characteristics, and flexibility of functionalization, the HCA scaffold likely
      represents an important advancement in the development of class II FBA inhibitors
      that can serve as viable preclinical candidates. 

PMID- 24325646
TI  - FOXE1 association with differentiated thyroid cancer and its progression.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) near thyroid transcription
      factor genes (FOXE1 rs965513/NKX2-1 rs944289) have been shown to be associated
      with differentiated thyroid cancer (DTC) in Caucasoid populations. We
      investigated the role of those SNPs in German patients with DTC and also extended
      our analysis to tumor stages and lymphocytic infiltration of the tumors (ITL).
      METHODS: Patients with DTC (n=243; papillary, PTC; follicular, FTC) and healthy
      controls (HC; n=270) were analyzed for the rs965513 and rs944289 SNPs. RESULTS:
      The case-control analysis for rs965513 SNP showed that the genotypes "AA," "AG,"
      and minor allele "A" were more frequent in patients with DTC than in HC
      (pronounced in PTC p(genotype)=0.000084, p(allele)=0.006 than FTC
      p(genotype)=0.29 and p(allele)=0.06). Furthermore, subgroup analysis of the DTC
      patients stratified for primary tumor stage (T1-T2, T3-T4), the absence or
      presence of regional lymph node metastases (N0, N1), for distant metastases (M0,
      M1), as well as for ITL, showed an association of rs965513 with stages T1-T2, T1
      T3, N1, and absence of ITL. The NKX2-1 SNP rs944289, however, was not associated
      with DTC. CONCLUSION: Our results confirm that the FOXE1 rs965513 SNP confers an
      increased risk for DTC in the German population, particularly allele "A" and the
      genotypes "AA" and "AG" for PTC. This increased risk was also observed in
      advanced tumor stages and absence of ITL, which may reflect the course of a more
      aggressive disease. The NKX2-1 rs944289 SNP, however, appears to play a secondary
      role in the development of DTC in the German population.

PMID- 24325648
TI  - Cross-reactivity between decellularized  porcine corneal lamellae for corneal 
      xenobridging and subsequent corneal  allotransplants.
AB  - The purpose of this study is to investigate cross-reactivity between hypertonic
      saline-treated decellularized porcine corneal lamellae for corneal xenobridging
      and subsequent corneal allotransplants. Five Chinese rhesus macaques, which had
      undergone anterior partial thickness corneal transplantation using hypertonic
      saline-treated decellularized porcine corneal lamellae in preceding experiments,
      were used as recipients for subsequent full-thickness corneal allografts. To
      determine whether sensitization of recipients to xenoantigens leads to cross
      reactivity against alloantigens, we compared; (i) allogeneic one-way mixed
      lymphocyte reaction (MLR) of peripheral blood mononuclear cells (PBMCs) from xeno
      sensitized recipients with that of PBMCs from naive rhesus macaques, and (ii)
      amounts of IgG antibodies that bound to the PBMCs of a rhesus panel (five
      monkeys) before and after xeno-sensitization. Graft survival and immunologic
      profiles including memory T-cell subsets and donor rhesus-specific antibodies
      were also evaluated. No hyperacute or acute rejection was observed within a month
      of subsequent allotransplantation in any recipient. Alloreactivity by MLR was not
      different between xeno-sensitized rhesus recipients and naive rhesus monkeys.
      Panel-reactive IgG antibodies were unchanged after xeno-sensitization, and no
      change in donor rhesus-specific antibodies was observed in any recipient. No
      significant changes in memory T-cell subsets were observed during the early post
      operative period in any recipient. Decellularized porcine corneal lamellae may
      not increase cross-reactivity to alloantigens, and thus, porcine corneal lamellae
      may be used as a bridge to subsequent corneal allografting.

PMID- 24325649
TI  - Safety and efficacy of a novel disposable sheathed gastroscopic system in
      clinical practice.
AB  - BACKGROUND AND AIM: Endoscopic examinations carry a potential risk of cross
      infection, and the traditional reprocessing method is time consuming. We
      evaluated the safety and efficacy of a novel disposable sheathed gastroscope
      system in clinical practice in comparison with the conventional gastroscope.
      METHODS: There were two phases in the study. In phase 1, 20 patients with
      hepatitis B were randomized into two groups: the sheathed group was examined with
      the novel disposable sheathed gastroscope (n = 10) and the conventional group
      with the conventional gastroscope (n = 10). Microbiologic tests were performed on
      each endoscope afterwards. In the second phase, 1120 patients were randomized
      again into the same two groups with 568 and 552 patients in the sheathed group
      and the conventional group, respectively. The time duration of the endoscopic
      procedure and reprocessing were measured. The pathology detection rate of
      endoscopic examinations, the patients' subjective feelings, and problems occurred
      during procedures were also recorded. RESULTS: The total instrument turn-around
      time in the phase 2 sheathed group (9.9 +/- 1.3 min) was significantly shorter
      than the conventional group (39.0 +/- 1.4 min, P = 0.000). The mean procedural
      time was slightly longer in the sheathed group than in the conventional group
      (4.9 +/- 1.4 vs 4.1 +/- 1.3 min, P = 0.000). However, the duration of endoscopic
      reprocessing was much shorter (4.9 +/- 0.2 vs 35 +/- 0.2 min, P = 0.000). No
      significant differences were observed in patient discomfort, optical clarity, or
      pathology detection rate. There were no complications in either group, and no
      microbial contamination was detected in phase 1 of the study. CONCLUSIONS:
      Compared with the conventional gastroscope, the novel disposable sheathed
      gastroendoscope is safe and more efficient in clinical practice.

PMID- 24325647
TI  - Antibiotic resistance, virulence determinants and production of biogenic amines
      among enterococci from ovine, feline, canine, porcine and human milk.
AB  - BACKGROUND: Recent studies have shown that mammalian milk represents a continuous
      supply of commensal bacteria, including enterococci. The objectives of this study
      were to evaluate the presence of enterococci in milk of different species and to
      screen them for several genetic and phenotypic traits of clinical significance
      among enterococci. RESULTS: Samples were obtained from, at least, nine porcine,
      canine, ovine, feline and human healthy hosts. Enterococci could be isolated, at
      a concentration of 1.00 * 10(2) -1.16 * 10(3) CFU/ml, from all the porcine
      samples and, also from 85, 50, 25 and 25% of the human, canine, feline and ovine
      ones, respectively. They were identified as Enterococcus faecalis, Enterococcus
      faecium, Enterococcus hirae, Enterococcus casseliflavus and Enterococcus durans.
      Among the 120 initial enterococcal isolates, 36 were selected on the basis of
      their different PFGE profiles and further characterized. MLST analysis revealed a
      wide diversity of STs among the E. faecalis and E. faecium strains, including
      some frequently associated to hospital infections and novel STs. All the E.
      faecalis strains possessed some of the potential virulence determinants (cad,
      ccf, cob, cpd, efaA(fs), agg2, gelE, cylA, esp(fs)) assayed while the E. faecium
      ones only harboured the efaA(fm) gene. All the tested strains were susceptible to
      tigecycline, linezolid and vancomycin, and produced tyramine. Their
      susceptibility to the rest of the antimicrobials and their ability to produce
      other biogenic amines varied depending on the strain. Enterococci strains
      isolated from porcine samples showed the widest spectrum of antibiotic
      resistance. CONCLUSIONS: Enterococci isolated from milk of different mammals
      showed a great genetic diversity. The wide distribution of virulence genes and/or
      antibiotic resistance among the E. faecalis and E. faecium isolates indicates
      that they can constitute a reservoir of such traits and a risk to animal and
      human health.

PMID- 24325650
TI  - Many-body effects in valleytronics: direct measurement of valley lifetimes in
      single-layer MoS2.
AB  - Single layer MoS2 is an ideal material for the emerging field of "valleytronics"
      in which charge carrier momentum can be finely controlled by optical excitation.
      This system is also known to exhibit strong many-body interactions as observed by
      tightly bound excitons and trions. Here we report direct measurements of valley
      relaxation dynamics in single layer MoS2, by using ultrafast transient absorption
      spectroscopy. Our results show that strong Coulomb interactions significantly
      impact valley population dynamics. Initial excitation by circularly polarized
      light creates electron-hole pairs within the K-valley. These excitons coherently
      couple to dark intervalley excitonic states, which facilitate fast electron
      valley depolarization. Hole valley relaxation is delayed up to about 10 ps due to
      nondegeneracy of the valence band spin states. Intervalley biexciton formation
      reveals the hole valley relaxation dynamics. We observe that biexcitons form with
      more than an order of magnitude larger binding energy compared to conventional
      semiconductors. These measurements provide significant insight into valley
      specific processes in 2D semiconductors. Hence they could be used to suggest
      routes to design semiconducting materials that enable control of valley
      polarization. 

PMID- 24325651
TI  - High-titre circulating tissue transglutaminase-2 antibodies predict small bowel
      villous atrophy, but decision cut-off limits must be locally validated.
AB  - Numerous studies suggest that high levels of circulating immunoglobulin (Ig)A
      tissue transglutaminase (TTG2) antibodies predict coeliac disease with high
      specificity. Accordingly, it has been suggested that duodenal biopsy may not be
      required routinely for diagnostic confirmation where quantitative serology
      identifies the presence of high antibody titres. However, defining a cut-off TTG2
      threshold is problematic, as the multiple available assay methods are not
      harmonized and most studies have been focused on the paediatric population.
      Recent paediatric guidelines proposed a TTG2 antibody diagnostic cut-off at 10 *
      the upper limit of normal (ULN) for the method; however, concerns remain about
      errors of generalization, between both methods and laboratories. In this study,
      we used retrospective laboratory data to investigate the relationship between
      TTG2 antibody levels and Marsh 3 histology in the seropositive population of
      adults and children at a single centre. Among 202 seropositive patients with
      corresponding biopsies, it was possible to define a TTG2 antibody cut-off with
      100% specificity for Marsh 3 histology, at just over 10 * ULN for the method.
      However, UK National External Quality Assurance Scheme returns during the study
      period showed a wide dispersion of results and poor consensus, both between
      methods and between laboratories using the same method. Our results support the
      view that high-titre TTG2 antibody levels have strong predictive value for
      villous atrophy in adults and children, but suggest that decision cut-offs to
      guide biopsy requirement will require local validation. TTG2 antibody assay
      harmonization is a priority, in order to meet the evolving requirements of
      laboratory users in this field.

PMID- 24325652
TI  - Initial reactions to tobacco and cannabis smoking: a twin study.
AB  - BACKGROUND AND AIMS: Initial subjective reactions to cannabis and tobacco,
      broadly classified as positive or negative, have previously been explored for
      their associations with onset and maintenance of subsequent abuse/dependence. We
      examine (i) the factorial architecture of self-reported initial reactions to
      cannabis and tobacco; (ii) whether these factors associate with concurrently
      reported age at onset of DSM-IV diagnosis of nicotine dependence and cannabis
      abuse/dependence; and (iii) estimate heritable variation in and covariation
      between the factors. DESIGN: Factorial and exploratory structural equation
      modeling was conducted to examine the factor structure of initial reactions. Cox
      proportional hazards modeling was employed to examine their association with time
      to onset of diagnosis of DSM-IV nicotine dependence and cannabis
      abuse/dependence. Classical twin modeling, using univariate and multivariate
      models, was used to parse variance in each factor (and the covariance between
      factors) to their additive genetic, shared environmental and non-shared
      environmental sources. SETTING AND PARTICIPANTS: General population sample of
      Caucasian female twins aged 18-32 years, with a life-time history of tobacco [n =
      2393] and cannabis [n = 1445] use. MEASUREMENT: Self-report of initial subjective
      reactions to tobacco (cigarettes) and cannabis the first time they were used and
      time to onset of life-time history of DSM-IV diagnosis of abuse (cannabis) and
      dependence (cannabis or nicotine). FINDINGS: Factors representing putatively
      positive and negative reactions to cannabis and tobacco emerged. Initial
      reactions to tobacco were associated with onset of DSM-IV diagnosis of nicotine
      dependence and cannabis abuse/dependence while initial reactions to cannabis were
      associated with onset of DSM-IV diagnosis of cannabis abuse/dependence alone.
      Genetic factors played a moderate role in each factor (heritability of 27-35%, P
      < 0.05), with the remaining variance attributed to individual-specific
      environment. Covariation across the factors indexing positive and negative
      initial reactions was attributable to genetic sources (0.18-0.58, P < 0.05) and
      to overlapping individual-specific environmental factors (-0.16 to 0.36, P <
      0.05). CONCLUSIONS: Initial subjective reactions to tobacco are associated with
      onset of DSM-IV diagnosis of nicotine dependence and cannabis abuse/dependence
      while initial subjective reactions to cannabis are only associated with onset of
      diagnosis of DSM-IV cannabis abuse/dependence. Genetic and environmental factors
      underpin the overlap across the factors representing initial reactions, both
      positive and negative.

PMID- 24325653
TI  - Health promoting schools and children's oral health related quality of life.
AB  - BACKGROUND: The study objective was to compare children's oral health related
      quality of life (OHRQoL) in schools with 6 years of implementation of a health
      promoting school model in Malaysia, i.e. the Doktor Muda Programme (DMP) and in
      schools without the DMP. METHODS: This report was part of a larger study to
      evaluate the DMP impact on schoolchildren's oral health knowledge, attitudes,
      behaviour, caries progression and OHRQoL. It was conducted in Negri Sembilan
      state. The sample comprised 3455, Year 6 (11-12 year old) children; 1282 from DMP
      (intervention) and 2173 from non-DMP (control) schools. The Malay Child-OIDP
      index was used to evaluate children's levels of oral impacts on 8 daily
      performances after 6 years of DMP implementation (2006-2011). Prevalence, score,
      impact intensity, causes and extent of impacts were compared. Chi-square and Mann
      Whitney tests were used in the data analysis. RESULTS: Overall response rate was
      95.1%. Prevalence of overall impacts was 57.8% and 60.8% (mean total impact score
      was 7.10 and 7.77) in the intervention and control group, respectively. The three
      most frequently affected performances in both groups were eating, cleaning teeth
      and emotional stability. Significantly less DMP children had oral impact on
      cleaning teeth (p = 0.034). The majority of children with impacts in both groups
      reported 'very little' to 'moderate' levels of impact intensity. Significantly
      more DMP children reported having 'very little' and 'little' levels of impact
      intensity on cleaning teeth (p = 0.037) and emotional stability (p = 0.020),
      respectively. Significantly less DMP children reported having 'very severe' level
      of impact intensity on speaking (p = 0.038). The most prevalent cause of impacts
      in both groups was toothache. Significantly less DMP children reported bleeding
      gums (p = 0.016) and presence of plaque/calculus as causes of impacts (p =
      0.032). About 75% of children with impacts in both groups reported having up to
      four daily performances affected. CONCLUSION: This study showed that the health
      promoting school model, i.e. the Doktor Muda Programme for primary schools in
      Malaysia had some positive impacts on 11-12 year old children's oral health
      related quality of life.

PMID- 24325654
TI  - Initial experiences of a novel self-retaining intracorporeal retractor device for
      urologic laparoendoscopic single-site surgery.
AB  - BACKGROUND AND PURPOSE: Laparoendoscopic single-site surgery (LESS) is a surgical
      option for a number of urologic operations, although it does carry technical
      limitations. One of the major obstacles in performing LESS is accomplishing
      optimal retraction of adjacent organs. The aim of this study was to investigate
      the feasibility of a novel self-retaining intracorporeal retractor device, the
      Internal Organ Retractor (IOR), and to describe our experience using this device
      in LESS. PATIENTS AND METHODS: A total of 23 patients who underwent LESS using
      IOR between December 2012 and July 2013 were identified. Among these patients, 11
      nephrectomies, 9 adrenalectomies, 1 pyeloplasty, and 2 nephroureterectomies were
      performed. Perioperative outcomes including operative time, complications related
      to use of the IOR, and amount of time needed for the application and removal of
      the IOR were measured during each operation. RESULTS: Adequate retraction was
      accomplished in all surgical cases. The IOR helped to maintain a consistent
      operative field throughout the surgery. A median application time of a single IOR
      was 85.0 (range 44.5-187.5) seconds and removal time was 50.0 (20-400) seconds.
      The median number of IOR sets used was 2.0 (range 1-4), and the median total
      application and removal time in a single operation were 170.0 (45-750) seconds
      and 95.0 (20-400) seconds, respectively. There were no perioperative
      complications associated with use of the IOR. CONCLUSIONS: The IOR provided
      satisfactory retraction during LESS, and its application/removal was
      uncomplicated and needed a minimal amount of time. The IOR reduced the need for
      additional laparoscopic ports for retraction. We believe that the IOR is a useful
      retraction tool for LESS and possibly multiport laparoscopic surgeries.

PMID- 24325656
TI  - New role for endothelin signalling during development.

PMID- 24325655
TI  - Effectiveness and feasibility of lowering playground density during recess to
      promote physical activity and decrease sedentary time at primary school.
AB  - BACKGROUND: This pilot study aimed at investigating the effectiveness of lowering
      playground density on increasing children's physical activity and decreasing
      sedentary time. Also the feasibility of this intervention was tested. METHODS:
      Data were collected in September and October 2012 in three Belgian schools in
      187, 9-12 year old children. During the intervention, playground density was
      decreased by splitting up recesses and decreasing the number of children sharing
      the playground. A within-subject design was used. Children wore accelerometers
      during the study week. Three-level (class - participant - measurement (baseline
      or intervention)) linear regression models were used to determine intervention
      effects. After the intervention week the school principals filled out a
      questionnaire concerning the feasibility of the intervention. RESULTS: The
      available play space was 12.18 +/- 4.19 m2/child at baseline and increased to
      24.24 +/- 8.51 m2/child during intervention. During the intervention sedentary
      time decreased (-0.58 min/recess; -3.21%/recess) and moderate-to-vigorous
      physical activity (+1.04 min/recess; +5.9%/recess) increased during recess and
      during the entire school day (sedentary time: -3.29%/school day; moderate-to
      vigorous physical activity +1.16%/school day). All principals agreed that
      children enjoyed the intervention; but some difficulties were reported.
      CONCLUSIONS: Lowering playground density can be an effective intervention for
      decreasing children's sedentary time and increasing their physical activity
      levels during recess; especially in least active children.

PMID- 24325657
TI  - Expression of the Tpanxb1 gene from Taenia pisiformis and its potential
      diagnostic value by dot-ELISA.
AB  - Cysticercosis, caused by the larvae of Taenia pisiformis, is a common disease in
      rabbits that results in economic losses. To date, there has been limited
      information available on the early detection of infection by this parasite. This
      study describes a dot-ELISA method based on an autologous antigen annexin B1
      (Tpanxb1). Its potential for serodiagnosis of rabbit cysticercosis was also
      evaluated. Western blot analysis revealed that the recombinant Tpanxb1 (rTpanxb1)
      protein could be specifically recognized by rabbit anti-sera. In serum trials,
      the antibodies could be detected by dot-ELISA using rTpanxb1 at 14 days post
      infection. The positive response was present for up to 49 days post-infection.
      Based on the necropsy results of 169 rabbit samples, the relative sensitivity and
      specificity of the dot-ELISA were 94.55% and 92.86%, respectively. This study
      provides a foundation for studying the immunological function of annexin and its
      application to control Taenia cestodes.

PMID- 24325658
TI  - Mothers' perceptions of their child's enrollment in a randomized clinical trial:
      poor understanding, vulnerability and contradictory feelings.
AB  - BACKGROUND: Little is known about the views of mothers when their children are
      invited to participate in randomized clinical trials (RCTs) investigating
      medicines and/or invasive procedures. Our goal was to understand mothers'
      perceptions of the processes of informed consent and randomization in a RCT that
      divided uncooperative children into three intervention groups (physical
      restraint, sedation, and general anesthesia) for dental rehabilitation. METHODS:
      This is a qualitative study based on semi-structured interviews with mothers
      accompanying children under 3 years old presenting severe early childhood caries.
      Their responses were analyzed using content analysis. RESULTS: We identified one
      major theme from 15 mothers' responses - "Understanding of, attitudes toward, and
      feelings about consenting to participate in a RCT involving advanced behavior
      guidance techniques and about randomization" - that was derived from the
      following subcategories: confusion in defining techniques, questions after
      signing the consent form, lack of knowledge about the techniques, acceptance or
      questioning of the drawing, sharing responsibility with the child during the
      drawing, and feelings of faith in God, fear, powerlessness to choose, and relief
      from or an increase in pressure. CONCLUSIONS: Despite mothers' misunderstanding,
      vulnerability, and contradictory feelings, they were willing to overlook their
      thoughts in order to complete their children's dental treatment.

PMID- 24325659
TI  - Translation and validation of Hindi version of Geriatric Oral Health Assessment
      Index.
AB  - OBJECTIVE: The aim of the study was to translate and validate the oral health
      related quality of life assessment tool named Geriatric Oral Health Assessment
      Index (GOHAI) into Hindi language for use in the Indian population. METHODOLOGY:
      The 12-item GOHAI questionnaire was translated into Hindi, back-translated and
      compared with the original English version. After pilot testing and appropriate
      changes, the Hindi version was administered to a group of 500 patients visiting
      the geriatric medicine clinic in All India Institute of Medical Sciences, New
      Delhi. The questionnaire was re-administered to 29 participants after a gap of
      minimum 7 days. The measures for reliability and validity were also assessed.
      RESULTS: Cronbach's alpha score (0.79) showed excellent internal consistency.
      Item-scale correlations varied from 0.06 to 0.75. Test-retest correlation on the
      29 patients showed excellent results (ranging from 0.748 to 0.946). Lower GOHAI
      scores were associated with patient's self-perception of nutritional status,
      perceptive need for prosthesis, number of posterior occluding pair of teeth.
      Higher GOHAI scores were seen with patients with removable prosthesis than with
      edentulous or partially edentulous participants. Age group was also found to be a
      significant factor for GOHAI scores. CONCLUSION: The Hindi version of GOHAI
      exhibits acceptable validity and reliability and can be used in the elderly
      Indian population as a measure of oral health-related quality of life.

PMID- 24325660
TI  - QuickView video preview software of colon capsule endoscopy: reliability in
      presenting colorectal polyps as compared to normal mode reading.
AB  - OBJECTIVE. Colon capsule endoscopy (CCE) proved to be highly sensitive in
      detection of colorectal polyps (CP). Major limitation is the time-consuming video
      reading. The aim of this prospective, double-center study was to assess the
      theoretical time-saving potential and its possible impact on the reliability of
      "QuickView" (QV), in the presentation of CP as compared to normal mode (NM).
      METHODS. During NM reading of 65 CCE videos (mean patient's age 56 years), all
      frames showing CPs were collected and compared to the number of frames presented
      by QV at increasing QV settings (10, 20, ... 80%). Reliability of QV in
      presenting polyps <6 mm and >=6 mm (significant polyp), and identifying patients
      for subsequent therapeutic colonoscopy, capsule egestion rate, cleansing level,
      and estimated time-saving potential were assessed. RESULTS. At a 30% QV setting,
      the QV video presented 89% of the significant polyps and 86% of any polyps with
      >=1 frame (per-polyp analysis) identified in NM before. At a 10% QV setting, 98%
      of the 52 patients with significant polyps could be identified (per-patient
      analysis) by QV video analysis. Capsule excretion rate was 74% and colon
      cleanliness was adequate in 85%. QV's presentation rate correlates to the QV
      setting, the polyp size, and the number of frames per finding. CONCLUSIONS.
      Depending on its setting, the reliability of QV in presenting CP as compared to
      NM reading is notable. However, if no significant polyp is presented by QV, NM
      reading must be performed afterwards. The reduction of frames to be analyzed in
      QV might speed up identification of candidates for therapeutic colonoscopy.

PMID- 24325662
TI  - Predictors of postpartum sexual activity and function in a diverse population of
      women.
AB  - INTRODUCTION: The purpose of this study was to identify predictors of postpartum
      sexual activity and functioning in a diverse population of women using the Sexual
      Health Outcomes in Women Questionnaire (SHOW-Q). METHODS: This was a prospective
      study of 160 postpartum women assessing relationships between demographic
      factors, mode of birth, depression, breastfeeding, and sexual activity and
      function. Questionnaires were administered over the telephone 8 to 10 weeks
      postpartum and in person 6 to 8 months postpartum. Primary outcomes were sexual
      activity at 8 to 10 weeks postpartum and global and subscale SHOW-Q scores at 6
      to 8 months postpartum; the primary predictor was mode of birth. Associations
      were assessed using multiple linear and logistic regression analyses. RESULTS:
      Seventy-five percent of this population (n = 140 at 8-10 weeks, n = 129 at 6-8
      months) gave birth vaginally, and 60.7% resumed sexual activity by 8 to 10 weeks
      postpartum. Only multiparity was associated with increased odds of having resumed
      sexual activity by 8 to 10 weeks postpartum (adjusted odds ratio [aOR], 2.44; P =
      .03), whereas older age was associated with decreased odds (aOR, 0.92; P = .02)
      of having resumed sexual activity. Women who were depressed (effect estimate, 
      13.3; P = .01), older (-1.1, P = .01), or exclusively breastfeeding (-16.5, P <
      .001) had significantly poorer sexual satisfaction, whereas multiparous women
      reported better sexual satisfaction (11.1, P = .03). A significant relationship
      between mode of birth and SHOW-Q scores did not emerge, although we did observe a
      trend toward lower SHOW-Q scores among women who underwent cesarean compared with
      those giving birth vaginally. DISCUSSION: Multiparity and younger age predict
      early resumption of sexual activity, whereas depression and breastfeeding are
      associated with poorer postpartum sexual functioning. The relationship between
      mode of birth and resumed sexual activity or postpartum sexual function remains
      uncertain.

PMID- 24325663
TI  - Minimally invasive transcrestal sinus floor elevation with deproteinized bovine
      bone or beta-tricalcium phosphate: a multicenter, double-blind, randomized,
      controlled clinical trial.
AB  - AIMS: To evaluate the outcomes of transcrestal sinus floor elevation (tSFE)
      performed with a minimally invasive procedure (Smart Lift technique) combined
      with the additional use of deproteinized bovine bone mineral (DBBM) or beta
      tricalcium phosphate (beta-TCP). METHODS: In a multicenter randomized controlled
      trial, 38 sites in 38 patients were treated with the Smart Lift technique in
      association with DBBM (n = 19) or beta-TCP (n = 19). The extent of the sinus lift
      (SL) and the height of the graft apical to the implant apex (aGH) were assessed
      on periapical radiographs taken immediately after surgery and at 6 months
      following surgery. RESULTS: (i) Substantial aGH and SL were observed immediately
      after surgery and at 6 months, with no significant differences between DBBM and
      beta-TCP groups; (ii) a significant graft remodelling was observed from post
      surgery to 6-months in the beta-TCP group and (iii) limited incidence of
      complications as well as limited post-operative pain and discomfort were
      associated with the use of both graft materials. CONCLUSIONS: The Smart Lift
      technique in conjunction with the additional use of either DBBM or beta-TCP may
      provide a substantial elevation of the maxillary sinus floor along with limited
      post-surgical complications and post-operative pain/discomfort.

PMID- 24325664
TI  - Invaded grassland communities have altered stability-maintenance mechanisms but
      equal stability compared to native communities.
AB  - Theory predicts that stability should increase with diversity via several
      mechanisms. We tested predictions in a 5-year experiment that compared low
      diversity exotic to high-diversity native plant mixtures under two irrigation
      treatments. The study included both wet and dry years. Variation in biomass
      across years (CV) was 50% lower in mixtures than monocultures of both native and
      exotic species. Growth among species was more asynchronous and overyielding
      values were greater during and after a drought in native than exotic mixtures.
      Mean-variance slopes indicated strong portfolio effects in both community types,
      but the intercept was higher for exotics than for natives, suggesting that
      exotics were inherently more variable than native species. However, this failed
      to result in higher CV's in exotic communities because species that heavily
      dominated plots tended to have lower than expected variance. Results indicate
      that diversity-stability mechanisms are altered in invaded systems compared to
      native ones they replaced. 

PMID- 24325666
TI  - Assessment of possible immunotoxicity of the antipsychotic drug clozapine.
AB  - OBJECTIVES: The immunomodulatory effects of clozapine (CLZ), antipsychotic drug,
      were investigated in vivo using female Balb/c mice. The main aim of this study
      was to evaluate the immunomodulatory effects of CLZ, antipsychotic drug,
      following daily intraperitoneal injection to female Balb/c mice over a period of
      21 days. METHODS: Mice were divided into five groups, eight animals per group.
      Group I, served as a control group, received only the vehicle. Groups II-V
      received a daily intraperitoneal dose of CLZ (1, 5, 10 and 20 mg/kg,
      respectively) over a period of 21 days. KEY FINDINGS: CLZ has shown a significant
      decrease in the animal body weight, and it showed a significant decrease in the
      percentage of circulating neutrophils and lymphocytes while circulating monocytes
      were increased. The immunotoxicity has been also assessed by evaluating spleen
      cellularity, humoral immune response to a foreign antigen using sheep red blood
      cells and delayed-type hypersensitivity reaction. The results showed a marked
      suppression in these responses in CLZ-treated mice compared with the control
      group. Detectable changes have also been noticed in the histology of the footpad
      tissue and spleen. CONCLUSIONS: Results showed significant immunomodulatory
      effects of CLZ when used in Balb/c mice.

PMID- 24325667
TI  - Mitochondrial genome of Monotrete leiurus (Osteichthyes: Tetraodontidae).
AB  - Monotrete leiurus is the only freshwater puffer founded in Nala River, which is a
      tributary of the Langcang-Mekong River in China. The complete mitochondrial
      genome sequence of the Monotrete leiurus is 16,448 bp long and consists of 13
      protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 control region (CR). The
      base composition of the genome is 29% A, 23.8% T, 31.8% C and 15.4% G and this
      composition shows a bias for A + T. The mitochondrial genes from Monotrete
      leiurus are overlapped in a total of 34 bp at seven locations and interleaved
      with a total of 64 bp intergenic spacers at 13 locations. The results can not
      only help clarify the classification problem in sibling freshwater puffers, but
      also provide information for their protection in the future.

PMID- 24325668
TI  - Complete mitochondrial genome organization of Schizothorax esocinus (Heckel,
      1838).
AB  - The complete mitochondrial genome of Schizothorax esocinus, an endemic coldwater
      fish of Himalayas, was determined for the first time. The genome is 16,583 bp in
      length and consists of 13 protein-coding genes, 22 tRNAs, 2rRNA genes and 1
      putative control region. The gene organization and its order were similar to
      other vertebrates. The overall base composition was; A 29.8%, G 17.8%, C 27%, T
      25.4%, A + T content 55.2% and the G + C content 44.8%. The control region was
      also consisted of a microsatellite locus (TA) 13 between 16,463 to 16,488 bp. The
      present study will provide the rationale for the management and conservation of
      S. esocinus.

PMID- 24325669
TI  - Complete mitochondrial genome organization of Schizopyge niger (Heckel, 1838).
AB  - The complete mitochondrial genome of Schizopyge niger, an endemic coldwater fish
      of Himalayas was determined for the first time. The genome is 16,585 bp in length
      and consists of 13 protein-coding genes, 22 tRNAs, 2rRNA genes and 1 putative
      control region. The gene organization and its order were similar to other
      vertebrates. The overall base composition was; A: 29.9%, G: 17.7%, C 27.1%, T
      25.3%, A + T content 55.2% and the G + C content 44.8%. The control region was
      also consisted of a microsatellite locus (TA)13 between 16,471 to 16,496 bp. The
      present study will provide the rationale for the management and conservation of
      S. niger.

PMID- 24325670
TI  - The complete mitochondrial genome of Alburnus chalcoides aralensis.
AB  - The complete mitochondrial genome of Alburnus chalcoides aralensis is 16,604 bp
      in length and includes 13 protein-coding genes, 2 ribosomal genes, 22 transfer
      RNA genes and 2 non-coding sequences. The major non-coding sequence (D-loop
      control region) contains five conserved sequence blocks (CSB-1, CSB-2, CSB-3, CSB
      D and CSB-F) and one termination associated sequence. The other non-coding
      sequence is the origin of light-strand replication, which has the potential to
      fold into a stable stem-loop secondary structure. The mitochondrial genomic
      sequence will help us study the conservation genetics and evolution of
      Cyprinidae.

PMID- 24325671
TI  - The complete mitochondrial genome sequence of white-spotted char (Salvelinus
      leucomaenis).
AB  - The complete sequence of the mitochondrial genome of the white-spotted char
      (Salvelinus leucomaenis) was determined to be 16,658 bp in length, which contains
      the control region (CR), the origin of light-strand replication (OL), 22 transfer
      RNA genes, 2 ribosomal genes and 13 protein-coding genes. Overall, base
      composition of the complete mitochondrial DNA was 28.20% A, 26.51% T, 28.39% C,
      16.90% G, with 54.71% AT.

PMID- 24325672
TI  - Complete mitochondrial genome of northern spotted barramundi, Scleropages
      jardinii.
AB  - We sequenced the complete mitogenome of northern spotted barramundi Scleropages
      jardinii, an ancestral bonytongue with economic and conservation value. The
      mitogenome is 16,670 bp in length with an A + T content of 52.9%, and contains 13
      protein-coding genes, 2rRNAs, 22 tRNAs and a control region. The gene order and
      arrangement is similar to that of other Osteoglossidae species, as is base
      composition and codon usage. These data will provide useful molecular information
      for phylogenetic relationships within the family Osteoglossidae species.

PMID- 24325673
TI  - Self-assembly and crystallization of hairy (f-star) and DNA-grafted nanocubes.
AB  - Nanoparticle superlattices are key to realizing many of the materials that will
      solve current technological challenges. Particularly important for their optical,
      mechanical or catalytic properties are superlattices of anisotropic
      (nonspherical) nanoparticles. The key challenge is how to program anisotropic
      nanoparticles to self-assemble into the relevant structures. In this Article,
      using numerical simulations, we show that "hairy" (f-star) or DNA grafted on
      nanocubes provides a general framework to direct the self-assembly into phases
      with crystalline, liquid crystalline, rotator, or noncrystalline phases with both
      long-range positional and orientational order. We discuss the relevance of these
      phases for engineering nanomaterials or micromaterials displaying precise
      orientational order, realization of dry superlattices as well as for the field of
      programmed self-assembly of anisotropic nanoparticles in general. 

PMID- 24325675
TI  - Antithrombotic drug does not affect the positive predictive value of an
      immunochemical fecal occult blood test.
AB  - BACKGROUND AND AIM: Antithrombotic drugs may affect the diagnostic performance of
      immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC)
      screening. The aim of the present study was to assess the effect of
      antithrombotic drugs on the diagnostic performance of iFOBT. METHODS: We analyzed
      1016 patients who underwent colonoscopy for positive iFOBT. Patients were
      classified as follows: patients who had advanced neoplasms detected and those who
      did not; patients who had cancers detected and those who did not; patients who
      had any neoplasms detected and those who did not. We compared the following
      factors between two paired groups: sex, age, endoscopists' experience, and
      antithrombotic drug usage. RESULTS: A total of 139 patients were taking
      antithrombotic drugs (13.7%). Advanced neoplasms, cancers, and any neoplasms were
      detected in 196 (19.3%), 59 (5.8%), and 490 (48.2%)patients, respectively. There
      were no higher detection rates in the antithrombotic drug (-) group than in the
      (+) group (advanced neoplasms: 19.3% vs 19.4%, P=1.000; cancers: 5.8% vs 5.8%,
      P=1.000; any neoplasms: 48.4% vs 47.5%, P=0.856). Multivariate logistic
      regression analysis revealed that none of aspirin, warfarin, or other
      antithrombotic drugs was a significant factor for advanced neoplasms (95% CI
      0.350-1.216, P=0.179; 95% CI 0.421-1.899, P=0.772; 95% CI 0.323-1.810, P=0.764,
      respectively). As to cancers and any neoplasms, no antithrombotic drug also
      proved to be a significant factor. CONCLUSION: The present study demonstrated
      that the positive predictive value of iFOBT was not affected by ongoing
      antithrombotic therapy.

PMID- 24325674
TI  - Acrolein modification impairs key functional features of rat apolipoprotein E:
      identification of modified sites by mass spectrometry.
AB  - Apolipoprotein E (apoE), an antiatherogenic apolipoprotein, plays a significant
      role in the metabolism of lipoproteins. It lowers plasma lipid levels by acting
      as a ligand for the low-density lipoprotein receptor (LDLr) family of proteins,
      in addition to playing a role in promoting macrophage cholesterol efflux in
      atherosclerotic lesions. The objective of this study is to examine the effect of
      acrolein modification on the structure and function of rat apoE and to determine
      the sites and nature of modification by mass spectrometry. Acrolein is a highly
      reactive aldehyde, which is generated endogenously as one of the products of
      lipid peroxidation and is present in the environment in pollutants such as
      tobacco smoke and heated oils. In initial studies, acrolein-modified apoE was
      identified by immunoprecipitation using an acrolein-lysine specific antibody in
      the plasma of 10-week old male rats that were exposed to filtered air (FA) or low
      doses of environmental tobacco smoke (ETS). While both groups displayed acrolein
      modified apoE in the lipoprotein fraction, the ETS group had higher levels in the
      lipid-free fraction compared with the FA group. This observation provided the
      rationale to further investigate the effect of acrolein modification on rat apoE
      at a molecular level. Treatment of recombinant rat apoE with a 10-fold molar
      excess of acrolein resulted in (i) a significant decrease in lipid-binding and
      cholesterol efflux abilities, (ii) impairment in the LDLr- and heparin-binding
      capabilities, and (iii) significant alterations in the overall stability of the
      protein. The disruption in the functional abilities is attributed directly or
      indirectly to acrolein modification yielding an aldimine adduct at K149 and K155
      (+38); a propanal adduct at K135 and K138 (+56); an N(epsilon)-(3
      methylpyridinium)lysine (MP-lysine) at K64, K67, and K254 (+76), and an
      N(epsilon)-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) derivative at
      position K68 (+94), as determined by matrix-assisted laser desorption/ionization
      time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). The loss of
      function may also be attributed to alterations in the overall fold of the protein
      as noted by changes in the guanidine HCl-induced unfolding pattern and to protein
      cross-linking. Overall, disruption of the structural and functional integrity of
      apoE by oxidative modification of essential lysine residues by acrolein is
      expected to affect its role in maintaining plasma cholesterol homeostasis and
      lead to dysregulation in lipid metabolism. 

PMID- 24325676
TI  - Monoclonal antibodies to various epitopes of hepatitis B surface antigen inhibit
      hepatitis B virus infection.
AB  - BACKGROUND AND AIM: Antibodies against the "a" determinant of hepatitis B surface
      antigen (HBsAg) are able to neutralize circulating hepatitis B virus (HBV)
      particles and prevent HBV infection. It has been proposed that a single amino
      acid exchange may allow the virus to escape the immune response. We used a set of
      monoclonal antibodies (MAbs) to investigate whether a single mutation may account
      for virus escape from humoral immunity. METHODS: Nine murine HBsAg-specific MAbs
      were raised. Reactivity of all antibodies with 14 recombinant mutants of HBsAg
      was assessed by ELISA. HBV infection of HepaRG cells was used to evaluate viral
      neutralization capacity of MAbs in vitro. RESULTS: All MAbs were able to inhibit
      the establishment of HBV infection in a dose-dependent fashion, but recognition
      of HBsAg variants varied. The MAbs were classified into three subgroups based on
      their pattern of reactivity to the HBsAg variants. Accordingly, three MAbs showed
      weak reactivity (< 40%) to variants with mutations within the first loop of "a"
      determinant, five MAbs displayed negligible binding to variants with mutations
      within the second loop, and one MAb lost its binding to variants having mutations
      in both loops of the "a" determinant. CONCLUSIONS: Our results indicate that
      antibodies against different epitopes of the "a" determinant of HBsAg are able to
      neutralize HBV. It seems that mutations within a single or a limited number of
      amino acids within this determinant can hardly result in viral escape. These
      results have important implications for the development of antibody-based
      therapies against HBV.

PMID- 24325679
TI  - Sexuality for women with spinal cord injury.
AB  - The authors conducted a review of the literature on women's sexuality after
      spinal cord injury, including studies from 1990 to 2011 retrieved from PubMed.
      Several facets of a woman's sexuality are negatively affected by after spinal
      cord injury, and consequently, sexual satisfaction has been shown to decrease,
      which also negatively affects quality of life. Neurogenic bladder is common after
      spinal cord injury, and the resulting urinary incontinence is a top therapeutic
      priority of this population. To improve sexual satisfaction and quality of life
      for women with spinal cord injury, future research needs to explore the effects
      of urinary incontinence on various aspects of sexuality. 

PMID- 24325680
TI  - Direct observation of aggregative nanoparticle growth: kinetic modeling of the
      size distribution and growth rate.
AB  - Direct observations of solution-phase nanoparticle growth using in situ liquid
      transmission electron microscopy (TEM) have demonstrated the importance of "non
      classical" growth mechanisms, such as aggregation and coalescence, on the growth
      and final morphology of nanocrystals at the atomic and single nanoparticle
      scales. To date, groups have quantitatively interpreted the mean growth rate of
      nanoparticles in terms of the Lifshitz-Slyozov-Wagner (LSW) model for Ostwald
      ripening, but less attention has been paid to modeling the corresponding particle
      size distribution. Here we use in situ fluid stage scanning TEM to demonstrate
      that silver nanoparticles grow by a length-scale dependent mechanism, where
      individual nanoparticles grow by monomer attachment but ensemble-scale growth is
      dominated by aggregation. Although our observed mean nanoparticle growth rate is
      consistent with the LSW model, we show that the corresponding particle size
      distribution is broader and more symmetric than predicted by LSW. Following
      direct observations of aggregation, we interpret the ensemble-scale growth using
      Smoluchowski kinetics and demonstrate that the Smoluchowski model quantitatively
      captures the mean growth rate and particle size distribution. 

PMID- 24325678
TI  - Microbial fingerprinting detects intestinal microbiota dysbiosis in Zebrafish
      models with chemically-induced enterocolitis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) involves a breakdown in interactions
      between the host immune response and the resident commensal microbiota. Recent
      studies have suggested gut physiology and pathology relevant to human IBD can be
      rapidly modeled in zebrafish larvae. The aim of this study was to investigate the
      dysbiosis of intestinal microbiota in zebrafish models with IBD-like
      enterocolitis using culture-independent techniques. RESULTS: IBD-like
      enterocolitis was induced by exposing larval zebrafish to trinitrobenzenesulfonic
      acid (TNBS). Pathology was assessed by histology and immunofluorescence. Changes
      in intestinal microbiota were evaluated by denaturing gradient gel
      electrophoresis (DGGE) and the predominant bacterial composition was determined
      with DNA sequencing and BLAST and confirmed by real-time polymerase chain
      reaction. Larval zebrafish exposed to TNBS displayed intestinal-fold architecture
      disruption and inflammation reminiscent of human IBD. In this study, we defined a
      reduced biodiversity of gut bacterial community in TNBS-induced colitis. The
      intestinal microbiota dysbiosis in zebrafish larvae with IBD-like colitis was
      characterized by an increased proportion of Proteobacteria (especially
      Burkholderia) and a decreased of Firmicutes(Lactobacillus group), which were
      significantly correlated with enterocolitis severity(Pearson correlation p <
      0.01). CONCLUSIONS: This is the first description of intestinal microbiota
      dysbiosis in zebrafish IBD-like models, and these changes correlate with TNBS
      induced enterocolitis. Prevention or reversal of this dysbiosis may be a viable
      option for reducing the incidence and severity of human IBD.

PMID- 24325681
TI  - Issues in using whole slide imaging for diagnostic pathology: "routine" stains,
      immunohistochemistry and predictive markers.
AB  - The traditional microscope, together with the "routine" hematoxylin and eosin (H
      & E) stain, remains the "gold standard" for diagnosis of cancer and other
      diseases; remarkably, it and the majority of associated biological stains are
      more than 150 years old. Immunohistochemistry has added to the repertoire of
      "stains" available. Because of the need for specific identification and even
      measurement of "biomarkers," immunohistochemistry has increased the demand for
      consistency of performance and interpretation of staining results. Rapid advances
      in the capabilities of digital imaging hardware and software now offer a
      realistic route to improved reproducibility, accuracy and quantification by
      utilizing whole slide digital images for diagnosis, education and research. There
      also are potential efficiencies in work flow and the promise of powerful new
      analytical methods; however, there also are challenges with respect to validation
      of the quality and fidelity of digital images, including the standard H & E
      stain, so that diagnostic performance by pathologists is not compromised when
      they rely on whole slide images instead of traditional stained tissues on glass
      slides.

PMID- 24325682
TI  - Immunohistochemical identification of aquaporin 2 in the kidneys of young beef
      cattle.
AB  - Aquaporin 2 (AQP2) is a small, integral tetrameric plasma membrane protein that
      is expressed in mammalian kidneys. The specific constitution of this protein and
      its selective permeability to water means that AQP2 plays an important role in
      hypertonic urine production. Immunolocalization of AQP2 has been studied in
      humans, monkeys, sheep, dogs, rabbits, rats, mice and adult cattle. We analyzed
      the expression of AQP2 in kidneys of 7-month-old Polish-Friesian var. black and
      white male calves. AQP2 was localized in the principal cells of collecting ducts
      in medullary rays penetrating the renal cortex and in the collecting ducts of
      renal medulla. AQP2 was expressed most strongly in the apical plasma membrane,
      but expression was observed also in the intracellular vesicles and basolateral
      plasma membrane. Our study provides new information concerning the
      immunolocalization of AQP2 in calf kidneys.

PMID- 24325683
TI  - Child-rated versus parent-rated quality of life of community-based obese children
      across gender and grade.
AB  - BACKGROUND: Quality of life (QoL), which can be examined using self-reports or
      parental reports, might help healthcare providers understand obese children's
      subjective well-being in several domains of life. Community-based obese children
      report their QoL lower than their parents do. However, the differences between
      child- and parent-reported QoL have neither been tested across gender and grade
      nor analyzed by item. This study probed the relationship between obesity and QoL
      item scores in children, and compared child-reported with parent-reported QoL
      stratified by gender and grade. METHODS: One hundred eighty-seven dyads of 8- to
      12-year-old children (60 obese, 127 normal-weight) and their parents were
      recruited. QoL was assessed using both child- and parent-reported Pediatric
      Quality of Life Inventory 4.0 (PedsQL) questionnaires. RESULTS: Regression
      analyses showed specific difficulties with physical and emotional QoL in third-
      and fourth-grade obese boys (beta = 0.278-0.620), and specific problems with
      social functioning in fifth- and sixth-grade obese girls (beta = 0.337-0.411).
      Moreover, parents seemed unaware of the specific difficulties that their children
      faced (beta = 0.274-0.435). CONCLUSIONS: Obese children seemed to have their
      difficulties from third to fifth grade, respectively, and their parents seemed
      unaware of them. Thus, parents need to be more aware of specific difficulties
      related to childhood obesity.

PMID- 24325684
TI  - Early experience with the first commercially available off-the-shelf
      multibranched endograft (t-branch) in the treatment of thoracoabdominal aortic
      aneurysms.
AB  - PURPOSE: To assess the feasibility and safety of the first commercially available
      off-the-shelf multibranched endograft for total endovascular repair of
      thoracoabdominal aortic aneurysms (TAAA). METHODS: Between November 2012 and May
      2013, 15 patients (10 men; mean age 70 years) with TAAA underwent implantation of
      the Zenith t-Branch device, which received European marketing approval in late
      2012. Three patients presented with symptomatic TAAAs, and 2 patients had a
      chronic Stanford type B dissection with false lumen expansion. In a retrospective
      review of the prospectively collected data, the primary endpoint was 30-day
      mortality from any cause; the primary outcome measure was technical success.
      Secondary endpoints were postoperative complications, including renal failure
      requiring dialysis, organ ischemia, and spinal cord ischemia. Radiological
      outcomes, such as any type of endoleak, further aneurysm expansion, and branch
      occlusion, were also assessed. RESULTS: Technical success was 100%, with all
      target vessels connected and patent. There was no renal function deterioration or
      organ ischemia. Paraplegia was observed in one patient despite cerebrospinal
      fluid drainage and monitoring. Four patients suffered from transient paraparesis,
      which was completely resolved before discharge. There was no in-hospital or 30
      day mortality. After a mean follow-up of 5 months, no patient has died, and there
      has been no branch occlusion or type I/III endoleaks. CONCLUSION: Use of the off
      the-shelf t-Branch device in the treatment of TAAAs is feasible and safe, with
      encouraging early clinical and radiological outcomes. Long-term results are
      necessary to evaluate the applicability and performance of this endograft in the
      urgent setting.

PMID- 24325685
TI  - Commentary: from bespoke to off-the-shelf: the t-branch stent-graft for total
      endovascular TAAA repair.

PMID- 24325686
TI  - Periscope endograft technique to revascularize the left subclavian artery during
      thoracic endovascular aortic repair.
AB  - PURPOSE: To present early and midterm results of the periscope endograft (PG)
      technique to maintain left subclavian artery (LSA) blood flow in thoracic
      endovascular aortic repairs (TEVAR) involving zone 3. METHODS: From April 2010 to
      January 2013, 14 consecutive high-risk patients (11 men; mean age 70+/-8 years,
      range 56-87) underwent TEVAR with the PG technique for 10 thoracic aortic
      aneurysms (TAA), 2 traumatic aortic ruptures, and 2 aortic dissections without a
      suitable landing zone (>2 cm distal to the LSA). Five procedures were performed
      emergently for rupture (3 TAAs and the 2 trauma cases). Two patients had a
      periscope deployed in an aberrant right subclavian artery. The periscope
      endografts were sized 1 to 2 mm larger than the branch artery at the intended
      landing zone. The caudal end was extended distal to the intended distal landing
      site of the thoracic stent-graft, which was usually deployed after the PG. Both
      the PG and thoracic stent-grafts were generally molded using the kissing balloon
      technique. Outcomes analyzed were immediate technical success, perioperative
      mortality and morbidity, aneurysm diameter change, and periscope endograft
      patency. RESULTS: Immediate technical success was 100%, with all procedures
      completed as planned. Perioperatively, one periscope occluded and one of the
      ruptured TAA patients died. One percutaneous access site hematoma required only
      conservative management. At a mean follow-up of 26+/-9 months (range 9-37), there
      was no additional PG occlusion. The Kaplan-Meier estimate of PG patency was 93%
      at 2 years. CONCLUSION: The periscope endograft is a simple technique to maintain
      perfusion to the LSA in cases where the aortic stent-graft crosses its ostium.
      The PG technique can be performed transfemorally and even percutaneously, and it
      can be applied to all supra-aortic branches. Early and midterm results are
      encouraging, but more experience and long-term results are mandatory before this
      technique can be widely recommended.

PMID- 24325687
TI  - Commentary: midterm results of thoracic endovascular aortic repair with periscope
      graft revascularization of the left subclavian artery.

PMID- 24325688
TI  - Influence of oversizing on outcome in thoracic endovascular aortic repair.
AB  - PURPOSE: To investigate the influence of stent-graft oversizing on device-related
      complications after thoracic endovascular aortic repair (TEVAR) for thoracic
      aortic aneurysm (TAA). METHODS: The study cohort was composed of patients
      enrolled in 4 clinical trials of the TAG thoracic stent-graft. A total of 337 TAA
      patients (222 men; mean age 72 years) treated in these trials had sufficient data
      for analysis of oversizing and post-procedure mortality and complications, such
      as endoleak, migration, rupture, and reinterventions. Mean oversizing at the
      proximal landing zone was 14.6% (range -3.4% to 39.7%). Patients were stratified
      based on the percentage of oversizing: <10% (n=85, group 1), 10%-20% (n=188,
      group 2), and >20% (n=64, group 3). RESULTS: Patients in group 1 had
      significantly larger preoperative proximal aortic diameters (32.6 vs. 31.3 vs.
      28.2 mm, respectively; p<0.001) and neck lengths (6.9 vs. 5.8 vs. 5.2 cm
      (p=0.035). Overall, type I endoleak was the most frequent complication during the
      first 30 days of follow-up (35, 10.4%), but the incidences did not differ among
      the 3 groups (10.6% vs. 11.2% vs. 7.8%, respectively; p=0.809). Over a mean
      follow-up of 41.8+/-20.7 months, there were no significant differences in the
      occurrence of device-related complications among the groups, though the incidence
      of type I endoleaks was lower in group 2 (9.4% vs. 3.2% vs. 7.8%, respectively;
      p=0.073). Cox proportional hazards modeling showed no difference in the time to
      type I endoleak among oversizing groups [group 1 vs. 2: HR 1.24, 95% CI 0.65 to
      2.36 (p=0.509) and group 3 vs. 2: HR 1.24, 95% CI 0.60 to 2.60 (p=0.562)].
      CONCLUSION: The percentage of oversizing did not significantly affect the
      incidence of device-related complications after TEVAR for TAA. Although
      oversizing may enhance the radial force and help maintain a good proximal seal,
      additional oversizing seemed not to improve the overall outcome in this analysis.
      The current guidelines regarding stent-graft oversizing for TAA seem appropriate,
      though the correct percentage remains to be determined.

PMID- 24325689
TI  - 4-French-compatible endovascular material is safe and effective in the treatment
      of femoropopliteal occlusive disease: results of the 4-EVER trial.
AB  - PURPOSE: To report the 1-year results of a prospective multicenter trial to
      evaluate the safety and efficacy of treating symptomatic femoropopliteal
      occlusive disease using 4-F-compatible materials and no closure device. METHODS:
      The non-randomized 4-EVER trial (4-F endovascular treatment approach to
      infrainguinal disease) was conducted at 5 European hospitals (ClinicalTrials.gov
      identifier NCT01413139). The protocol mandated the use of only 4-F sheaths, self
      expanding nitinol stents (Astron Pulsar or Pulsar-18 stent), and balloons from a
      single manufacturer. Between June 2010 and June 2011, 120 symptomatic patients
      (82 men; mean age 71+/-9.7 years, range 47-90), primarily claudicants, treated
      for 120 femoropopliteal lesions (>90% TASC A/B) were enrolled. The mean lesion
      length was 71.0+/-45.9 mm. Follow-up evaluations were scheduled on day 1 and at
      1, 6, 12, and 24 months. A duplex ultrasound was performed on all follow-up
      visits to determine vessel patency (primary outcome measure at 1 year), and
      biplanar radiography was performed at 12 and 24 months to assess stent fracture.
      RESULTS: Stents were successfully implanted in all patients: an Astron Pulsar
      stent in 70 (58.3%) lesions and a Pulsar-18 stent in 46 (38.3%); 4 (3.3%)
      patients had both stents implanted for flow-limiting dissection after
      predilation. No closure devices were used; the mean manual compression time was
      8.1 minutes (2-15). Four (3.3%) patients developed significant hematoma at the
      puncture site, but none required surgical repair. The overall 12-month primary
      patency rate was 81.4%: 85.2% for the Astron Pulsar and 73.4% for the Pulsar-18
      (p=0.236). Freedom from target lesion revascularization at 12 months for the
      entire cohort was 89.3%. CONCLUSION: Compared to published historical data for
      superficial femoral artery type A/B lesion stenting using 6-F devices, the 4-F
      devices applied in this trial showed similar patency at 12 months, fewer access
      site complications, and shorter manual compression times, supporting the
      supposition that 4-F endovascular treatment is safe and effective.

PMID- 24325690
TI  - Commentary: voyage to miniaturization in lower limb artery intervention.

PMID- 24325691
TI  - SUMMIT registry: one-year outcomes after implantation of the EPIC self-expanding
      nitinol stent in the femoropopliteal segment.
AB  - PURPOSE: To evaluate the efficacy and safety of the EPIC self-expanding nitinol
      stent in patients with femoropopliteal occlusive disease. METHODS: The
      prospective, multicenter, nonrandomized SUMMIT study (ClinicalTrials.gov
      identifier NCT01336101) enrolled 100 patients (76 men; mean age 67.6 years) with
      symptomatic de novo femoropopliteal disease undergoing angioplasty and subsequent
      implantation of EPIC stents from April 2011 to October 2011. The mean lesion
      length was 69.5+/-40.5 mm; 29 of the lesions were total occlusions. Clinical
      examination and duplex sonography were prospectively performed after 6 and 12
      months. The primary endpoint was in-stent restenosis as assessed by duplex
      ultrasound (peak systolic velocity ratio >=2.5). Further outcome measures were
      patency rates, improvement in the Rutherford category and ankle-brachial index
      (ABI), as well as stent integrity based on plain radiography. RESULTS: A residual
      stenosis <30% was achieved in all procedures. The primary patency rates were
      96.8% after 6 months and 85.1% at 1 year. The secondary patency rates were 97.9%
      and 91.2% at the same intervals. The 1-year binary >50% restenosis rate was
      15.7%. Freedom from target lesion revascularization at 1 year was 92.3%. Between
      baseline and the 12-month follow-up, the mean ABI increased from 0.73 to 0.96,
      and the mean Rutherford category decreased from 2.9 to 1.0 (p<0.001 for both
      comparisons). Plain radiographs from 86 patients at the 12-month examination
      confirmed the absence of stent fractures. CONCLUSION: The outcome of the SUMMIT
      registry demonstrates that the EPIC self-expanding nitinol vascular stent is a
      safe and effective device for treating peripheral artery disease in the
      femoropopliteal segment.

PMID- 24325692
TI  - Commentary: nitinol stents for femoropopliteal disease: what is the view from the
      SUMMIT?

PMID- 24325693
TI  - Final results of the Chronic Total Occlusion Crossing With the Ocelot System II
      (CONNECT II) study.
AB  - PURPOSE: To evaluate the safety and effectiveness of the optical coherence
      tomography-guided Ocelot catheter to cross femoropopliteal chronic total
      occlusions (CTOs). METHODS: The CONNECT II study was a prospective, multicenter,
      non-randomized single-arm study of the safety and effectiveness of the Ocelot
      catheter in CTO crossing. Key inclusion criteria were a 99% to 100% stenosed
      femoropopliteal segment, lesion length between 1 and 30 cm, and resistance to
      guidewire crossing. The main exclusion criterion was a severely calcified target
      vessel. The primary safety endpoint was 30-day major adverse events (MAE), while
      the primary effectiveness endpoint was successful CTO crossing (i.e., guidewire
      placement in the distal true lumen) with the Ocelot catheter. Endpoint analysis
      was based on pre-specified objective performance criteria. Between February and
      June 2012, 100 patients (55 men; mean age 69 years) were enrolled. Most of the
      CTOs (94%) were in the superficial femoral artery (SFA); mean lesion length was
      16.6+/-9.3 cm. RESULTS: Through 30 days, 2 patients experienced MAE (significant
      perforations) related to the Ocelot catheter. The Ocelot catheter successfully
      crossed 97% of target CTOs either alone (72%), in conjunction with an assist
      device (18%), or in conjunction with a re-entry device (7%). Both primary safety
      and effectiveness endpoints were met. CONCLUSION: The Ocelot catheter with
      optical coherence tomography guidance offers physicians a reliable option for
      crossing femoral and popliteal chronic total occlusions with low MAE rates.

PMID- 24325694
TI  - Midterm outcomes of subintimal angioplasty supported by primary proximal stenting
      for chronic total occlusion of the superficial femoral artery.
AB  - PURPOSE: To investigate the midterm outcomes of subintimal angioplasty in
      occluded superficial femoral arteries (SFA) and evaluate the clinical and
      procedural factors affecting these results. METHODS: Between April 2004 and April
      2012, 150 patients (122 men; mean age 69+/-10 years) with chronic total
      occlusions in the SFA underwent subintimal angioplasty with primary stenting in
      172 limbs. The average lesion length was 22.6+/-8.5 cm. Stents were routinely
      implanted at the proximal entry into the subintimal channel. The primary endpoint
      was binary restenosis. RESULTS: Technical success was achieved in 161 (94%)
      limbs; there were no procedure-related deaths or complications requiring surgery,
      but distal embolization and arterial perforation occurred in 2 and 4 limbs,
      respectively. The cumulative freedom from binary restenosis rates at 1 and 3
      years were 77% and 59%, respectively, in the entire study group. The 96 patients
      without critical limb ischemia (CLI) had significantly higher patency rates at 1
      and 3 years (84% and 66%, respectively) than the 54 patients with CLI (66% and
      43%, respectively; p=0.011). Based on multivariate analysis, a larger number of
      stents, lower post-procedure ankle-brachial index, and lower body mass index were
      each independent predictors of binary restenosis. CONCLUSION: Subintimal
      angioplasty with routine stenting at the proximal stump is safe and effective for
      the treatment of chronic total SFA occlusions.

PMID- 24325695
TI  - High-grade, non-flow-limiting dissections do not negatively impact long-term
      outcome after paclitaxel-coated balloon angioplasty: an additional analysis from
      the THUNDER study.
AB  - PURPOSE: To investigate the impact of using paclitaxel-coated balloons (PCB) on
      outcome after post-angioplasty dissection in femoropopliteal arteries. METHODS:
      The angiograms obtained in the THUNDER study (ClinicalTrials.gov identifier
      NCT00156624) were analyzed to compare degrees of dissection and angiographic
      parameters between the control (uncoated balloons, n=43) and treatment (PCBs,
      n=43) groups before and after the intervention and at 6-month follow-up.
      Furthermore, target lesion revascularizations (TLR) were documented up to 2
      years. RESULTS: In each group, 24 (56%) patients had a dissection after the
      intervention. At the 6-month follow-up, patients with dissection of any grade
      after treatment with PCBs had significantly less late lumen loss (0.4 mm) than
      patients with dissection after treatment with uncoated balloons (1.9 mm, p=0.001)
      and a lower degree of stenosis (20% vs. 51%, respectively; p=0.003). Patients
      with severe dissection (grades C, D, or E) especially seemed to benefit from the
      PCBs, with late lumen loss of 0.4 mm vs. 2.4 mm for controls (p=0.05). The binary
      restenosis rate was also markedly lower in the PCB group (20%) than in the
      uncoated group (55%, p=0.02). In the 2-year follow-up, TLR was performed in 56%
      of patients in the control group compared to 10% of patients in the PCB group
      (p=0.002). CONCLUSION: The results of this subgroup analysis suggest that
      patients with dissection following treatment with a paclitaxel-coated balloon
      have a very acceptable outcome and stent implantation is not necessary as long as
      the dissection does not result in acute flow limitation.

PMID- 24325696
TI  - Commentary: how do we deal with dissection after angioplasty?

PMID- 24325697
TI  - Treatment of chronic SFA in-stent occlusion with combined laser atherectomy and
      drug-eluting balloon angioplasty in patients with critical limb ischemia: a
      single-center, prospective, randomized study.
AB  - PURPOSE: To compare the safety and efficacy of laser debulking (LD) and drug
      eluting balloon (DEB) angioplasty to treatment with DEB angioplasty alone in
      patients affected by critical limb ischemia (CLI) and superficial femoral artery
      (SFA) chronic stent occlusion in a prospective, randomized study. METHODS: Among
      448 CLI patients treated from December 2009 to March 2011, 48 patients (39 men;
      mean age 72.7+/-7.8 years) with chronic SFA in-stent occlusion were randomly
      assigned to treatment using LD+DEB (n=24) or DEB angioplasty alone (n=24).
      Patency at 12 months was the primary outcome measure; secondary outcomes were
      target lesion revascularization (TLR) and clinical success at 12 months. RESULTS:
      In the LD+DEB group, the patency rates at 6 and 12 months (91.7% and 66.7%,
      respectively) were significantly higher (p=0.01) than in the DEB only patients
      (58.3% and 37.5%, respectively). TLR at 12 months was 16.7% in the LD+DEB group
      and 50% in the DEB only group (p=0.01). Two (8%) patients needed major
      amputations in the LD+DEB group vs. 11 (46%) in the DEB only group at 12 months
      (p=0.003). CONCLUSION: In this small initial experience, combined treatment with
      LD and DEB angioplasty is correlated with better outcomes in CLI patients with
      occluded SFA stents.

PMID- 24325698
TI  - Commentary: laser debulking and drug-eluting balloons for in-stent restenosis: a
      light at the end of the tunnel?

PMID- 24325699
TI  - Cost-effectiveness analysis of paclitaxel-coated balloons for endovascular
      therapy of femoropopliteal arterial obstructions.
AB  - PURPOSE: To explore the cost-effectiveness of using drug-eluting balloon (DEB)
      angioplasty for the treatment of femoropopliteal arterial lesions, which has been
      shown to significantly lower the rates of target lesion revascularization (TLR)
      compared with standard balloon angioplasty (BA). METHODS: A simplified decision
      analytic model based on TLR rates reported in the literature was applied to
      baseline and follow-up costs associated with in-hospital patient treatment during
      1 year of follow-up. Costs were expressed in Swiss Francs (sFr) and calculated
      per 100 patients treated. Budgets were analyzed in the context of current
      SwissDRG reimbursement figures and calculated from two different perspectives: a
      general budget on total treatment costs (third-party healthcare payer) as well as
      a budget focusing on the physician/facility provider perspective. RESULTS: After
      1 year, use of DEB was associated with substantially lower total inpatient
      treatment costs when compared with BA (sFr 861,916 vs. sFr 951,877) despite the
      need for a greater investment at baseline related to higher prices for DEBs. In
      the absence of dedicated reimbursement incentives, however, use of DEB was shown
      to be the financially less favorable treatment approach from the
      physician/facility provider perspective (12-month total earnings: sFr 179,238 vs.
      sFr 333,678). CONCLUSION: Use of DEBs may be cost-effective through prevention of
      TLR at 1 year of follow-up. The introduction of dedicated financial incentives
      aimed at improving DEB reimbursements may help lower total healthcare costs.

PMID- 24325700
TI  - Commentary: aligning incentives of payer, facility, and provider: the lynchpin of
      providing more cost-effective care.

PMID- 24325701
TI  - Quantification of popliteal artery deformation during leg flexion in subjects
      with peripheral artery disease: a pilot study.
AB  - PURPOSE: To quantify the in vivo deformations of the popliteal artery during leg
      flexion in subjects with clinically relevant peripheral artery disease (PAD).
      METHODS: Five patients (4 men; mean age 69 years, range 56-79) with varying
      calcification levels of the popliteal artery undergoing endovascular
      revascularization underwent 3-dimensional (3D) rotational angiography. Image
      acquisition was performed with the leg straight and with a flexion of 70 degrees
      /20 degrees  in the knee/hip joints. The arterial centerline and the
      corresponding branches in both positions were segmented to create 3D
      reconstructions of the arterial trees. Axial deformation, twisting, and
      curvatures were quantified. Furthermore, the relationships between the
      calcification levels and the deformations were investigated. RESULTS: An average
      shortening of 5.9%+/-2.5% and twist rate of 3.8+/-2.2 degrees /cm in the
      popliteal artery were observed. Maximal curvatures in the straight and flexed
      positions were 0.12+/-0.04 cm(-1) and 0.24+/-0.09 cm(-1), respectively. As the
      severity of calcification increased, the maximal curvature in the straight
      position increased from 0.08 to 0.17 cm(-1), while an increase from 0.17 to 0.39
      cm(-1) was observed for the flexed position. Axial elongations and arterial
      twisting were not affected by the calcification levels. CONCLUSION: The popliteal
      artery of patients with symptomatic PAD is exposed to significant deformations
      during flexion of the knee joint. The severity of calcification directly affects
      curvature, but not arterial length or twisting angles. This pilot study also
      showed the ability of rotational angiography to quantify the 3D deformations of
      the popliteal artery in patients with various levels of calcification.

PMID- 24325702
TI  - Outcome of thrombolysis and thrombectomy for thrombosed endografts inserted in
      the superficial femoral artery for occlusive disease.
AB  - PURPOSE: To evaluate the efficacy and outcome of thrombolysis and thrombectomy
      for thrombosed polytetrafluoroethylene stent-grafts inserted in the superficial
      femoral artery (SFA) for occlusive disease. METHODS: A retrospective review was
      conducted of 79 consecutive patients with a thrombosed SFA endograft between
      November 2001 and December 2011. Of these, 46 (58%) were treated with
      thrombolysis (n=40, 87%) or thrombectomy (n=6, 13%) and form the study group (33
      men; median age 66.8 years, range 30-80). Median time from stent-graft insertion
      to thrombosis was 3 months (range 0-53). RESULTS: Thrombolysis was successful in
      38 (95%) patients over a mean 24 hours (range 3-48); one patient had failed lysis
      and another died during lytic treatment. Thrombectomy was successful in all 6
      patients. Thrombosis without a causal lesion was significantly more common in
      occlusions that presented <30 days after insertion (p=0.01). Over a median follow
      up of 14 months (range 1-69), reinterventions were performed for restenosis in 12
      patients and reocclusion in 14 patients, all within 18 months after thrombolytic
      treatment. More than a third of patients (16/45) had definitive failures (2/6
      from the thrombectomy group); 4 were treated conservatively (no/minor symptoms)
      and 12 had bypass grafts. Three (7%) patients eventually required a major
      amputation. The primary, assisted primary, and secondary patency rates of
      thrombolysis at 6 months were 56%, 56%, and 68%, respectively. Secondary patency
      for the entire cohort was 58% at 1 year. CONCLUSION: Thrombolysis and
      thrombectomy of thrombosed endografts in the SFA is effective and safe. Patency
      rates after treatment are moderate, but prolonged secondary patency can be
      achieved.

PMID- 24325703
TI  - Differences in patient selection and outcomes between SilverHawk atherectomy and
      laser ablation in the treatment of femoropopliteal in-stent restenosis: a
      retrospective analysis from a single center.
AB  - PURPOSE: To analyze differences in the application and outcomes of SilverHawk
      atherectomy (SH) and excimer laser ablation (ELA) in the treatment of
      femoropopliteal in-stent restenosis (ISR) in an unselected cohort of patients
      treated at a single center. METHODS: Between January 2005 and June 2010, 81
      consecutive patients (46 men; mean age 69.1 years, range 43-86) underwent
      directional atherectomy (41 SH, 40 ELA) for femoropopliteal ISR lesions. Data
      were reviewed retrospectively on procedural outcomes, major adverse events, and 1
      year target lesion revascularization (TLR) obtained from medical records and
      supplemented with telephone calls. The primary endpoint was symptom-driven TLR at
      1 year; secondary endpoints were death and amputation. RESULTS: ELA was utilized
      more frequently than SH in longer lesions (210.4+/-104 vs. 126.2+/-79.3 mm,
      respectively; p=0.001), subacute presentation (55% vs. 14.6%, p=0.001), TASC D
      lesions (47.5% vs. 12.2%), and in patients with more angiographic thrombus (42.5%
      vs. 4.9%, p=0.001). Final angiographic success (<30% residual narrowing post
      final treatment) was similar between ELA and SH (92.5% vs. 100%, respectively,
      p=0.12). Bailout stenting was significantly higher with ELA vs. SH (50.0% vs.
      24.4%, p=0.022). At 1 year, TLR had occurred in 48.7% of the ELA patients vs.
      31.7% of the SH cases (p=0.171). Regression analysis confirmed that SH was a
      predictor of TLR at 1 year (hazard ratio 2.679, 95% CI 1.015 to 7.073, p=0.047).
      CONCLUSION: Both SH and ELA continue to have a high TLR rate in treating ISR of
      the femoral and popliteal arteries. A higher rate of delayed failure is seen with
      SH and an earlier, steeper loss of TLR-free survival is seen with ELA.

PMID- 24325704
TI  - Clinical outcomes after crossed-limb vs. conventional endograft configuration in
      endovascular AAA repair.
AB  - PURPOSE: To report a case controlled analysis of endovascular aneurysm repair
      (EVAR) outcomes using the crossed-limb (CxL) endovascular configuration vs. the
      straight-limb configuration (SLC). METHODS: From January 2007 to July 2012, 27
      patients (25 men; mean age 73.7+/-7.2 years, range 53-82) were treated by EVAR
      with the CxL technique. These patients were matched anatomically with 27 patients
      (27 men; mean age 72.4+/-7.4 years, range 52-86) who underwent EVAR using the
      same endograft and the standard SLC within a +/-6-month period. Primary outcome
      measures included technical and clinical success and freedom from graft limb
      thrombosis, any type of endoleak, early or late secondary interventions, and
      aneurysm-related death estimated using the Kaplan-Meier method. RESULTS: The
      median follow-up periods for the CxL and SLC groups were 29.9 (range 6-54) and
      33.5 (range 6-59) months, respectively (p=0.81). The technical success rate was
      100% in both groups, but mean procedure times were significantly longer in the
      CxL group (116.3 vs. 90.7 minutes, p=0.035). Twelve intraoperative endoleaks (3
      each for types Ia, Ib, II, and IV) occurred but without any difference between
      groups (p=0.51). One CxL group patient died in the early postoperative period
      (aneurysm-related) and another had an early graft limb thrombosis. One late type
      Ib intraoperative endoleak was recorded in the SLC group (p=0.51). For the CxL
      vs. SLC groups, the 1-year rates for freedom from endograft limb thrombosis (94%
      vs. 96%), any type of endoleak (96% vs. 96%), early or late reintervention (94%
      vs. 96%), and aneurysm-related death (94% vs. 96%) were not significantly
      different. Respective values at 36 months were 82% vs. 82%, 85% vs. 84%, 81% vs.
      78%, and 83% vs. 84% (p>0.05). Clinical success rates at 12 months for the CxL
      and SLC groups were 91% and 100% (p>0.05), respectively, whereas at 36 months,
      the rates were 83% and 90% (p>0.05). CONCLUSION: No difference was found between
      the crossed-limb technique and the conventional endograft position as regards
      short- or midterm clinical outcomes.

PMID- 24325705
TI  - 3D printing of an aortic aneurysm to facilitate decision making and device
      selection for endovascular aneurysm repair in complex neck anatomy.
AB  - PURPOSE: To describe rapid prototyping or 3-dimensional (3D) printing of
      aneurysms with complex neck anatomy to facilitate endovascular aneurysm repair
      (EVAR). CASE REPORT: A 75-year-old man had a 6.6-cm infrarenal aortic aneurysm
      that appeared on computed tomographic angiography to have a sharp neck angulation
      of ~90 degrees . However, although the computed tomography (CT) data were
      analyzed using centerline of flow, the true neck length and relations of the
      ostial origins were difficult to determine. No multidisciplinary consensus could
      be reached as to which stent-graft to use owing to these borderline features of
      the neck anatomy. Based on past experience with rapid prototyping technology, a
      decision was taken to print a model of the aneurysm to aid in visualization of
      the neck anatomy. The CT data were segmented, processed, and converted into a
      stereolithographic format representing the lumen as a 3D volume, from which a
      full-sized replica was printed within 24 hours. The model demonstrated that the
      neck was adequate for stent-graft repair using the Aorfix device. CONCLUSION:
      Rapid prototyping of aortic aneurysms is feasible and can aid decision making and
      device delivery. Further work is required to test the value of 3D replicas in
      planning procedures and their impact on procedure time, radiation dose, and
      procedure cost.

PMID- 24325706
TI  - Endoluminal stent-graft relining of visceral artery bypass grafts to treat
      perigraft seroma.
AB  - PURPOSE: To describe the endovascular treatment of intra-abdominal perigraft
      seromas associated with small-caliber expanded polytetrafluoroethylene (ePTFE)
      grafts. CASE REPORTS: Two patients who underwent hybrid repair of
      thoracoabdominal aortic aneurysms in which renovisceral bypass grafts were
      implanted presented with large, symptomatic perigraft seromas. The 5- to 8-mm
      diameter ePTFE bypass grafts believed to be involved in the seromas were
      successfully relined with self-expanding Viabahn stent-grafts in percutaneous
      procedures. The patients' symptoms were relieved, and imaging follow-up (18 and
      10 months, respectively) has shown near complete resorption of the seromas.
      CONCLUSION: It is expected that this minimally invasive technique could be very
      valuable in treating aortic, renovisceral, and peripheral perigraft seroma.

PMID- 24325707
TI  - Aortic aneurysm rupture following treatment with flow-diverting multilayer
      stents.

PMID- 24325708
TI  - Reply:.

PMID- 24325709
TI  - Urgent endovascular treatment of a non-atherosclerotic penetrating aortic ulcer
      complicated by an aortic dissection.

PMID- 24325711
TI  - Skewed B cell differentiation affects lymphoid organogenesis but not T cell
      mediated autoimmunity.
AB  - B cell receptor (BCR) signalling determines B cell differentiation and may
      potentially alter T cell-mediated immune responses. In this study we used two
      transgenic strains of BCR-deficient mice expressing Epstein-Barr virus latent
      membrane protein (LMP)2A in B cells, where either follicular and marginal zone
      differentiation (D(H)LMP2A mice) or B-1 cell development (V(H)LMP2A mice) were
      supported, and evaluated the effects of skewed B lymphocyte differentiation on
      lymphoid organogenesis and T cell responses in vivo. Compared to wild-type
      animals, both transgenic strains displayed alterations in the composition of
      lymphoid organs and in the dynamics of distinct immune cell subsets following
      immunization with the self-antigen PLP185-206. However, ex-vivo T cell
      proliferation to PLP185-206 peptide measured in immunized D(H)LMP2A and V(H)LMP2A
      mice was similar to that detected in immunized control mice. Further, clinical
      expression of experimental autoimmune encephalitis in both LMP2A strains was
      identical to that of wild-type mice. In conclusion, mice with skewed B cell
      differentiation driven by LMP2A expression in BCR-negative B cells do not show
      changes in the development of a T cell mediated disease model of autoimmunity,
      suggesting that compensatory mechanisms support the generation of T cell
      responses.

PMID- 24325712
TI  - Conscious and unconscious processing of facial expressions: evidence from two
      split-brain patients.
AB  - We investigated how the brain's hemispheres process explicit and implicit facial
      expressions in two 'split-brain' patients (one with a complete and one with a
      partial anterior resection). Photographs of faces expressing positive, negative
      or neutral emotions were shown either centrally or bilaterally. The task
      consisted in judging the friendliness of each person in the photographs. Half of
      the photograph stimuli were 'hybrid faces', that is an amalgamation of filtered
      images which contained emotional information only in the low range of spatial
      frequency, blended to a neutral expression of the same individual in the rest of
      the spatial frequencies. The other half of the images contained unfiltered faces.
      With the hybrid faces the patients and a matched control group were more
      influenced in their social judgements by the emotional expression of the face
      shown in the left visual field (LVF). When the expressions were shown explicitly,
      that is without filtering, the control group and the partially callosotomized
      patient based their judgement on the face shown in the LVF, whereas the complete
      split-brain patient based his ratings mainly on the face presented in the right
      visual field. We conclude that the processing of implicit emotions does not
      require the integrity of callosal fibres and can take place within subcortical
      routes lateralized in the right hemisphere. 

PMID- 24325713
TI  - Regret in the context of unobtained rewards in criminal offenders.
AB  - In this study, we investigated whether differences in the experience of regret
      may be a potential explanation for damaging behaviours associated with
      psychopathy and criminal offending. Participants were incarcerated offenders (n =
      60) and non-incarcerated controls (n = 20). Psychopathic traits were
      characterised with the Psychopathic Checklist: Screening Version. Regret was
      assessed by responses to outcomes on a simulated gambling task. Incarcerated
      offenders experienced a reduced sense of regret as compared to non-incarcerated
      controls. We obtained some evidence that specific psychopathic factors and facets
      could differentially relate to the experience and use of emotions. Our data
      provide initial evidence of important associations between negative emotions and
      decision behaviour in the context of criminal offending. 

PMID- 24325714
TI  - Sex and violence in fairy tales.

PMID- 24325715
TI  - Statement on the health of people seeking asylum.

PMID- 24325716
TI  - Should intravenous immunoglobulin be used in infants with isoimmune haemolytic
      disease due to ABO incompatibility?
AB  - The use of intravenous immunoglobulin in isoimmune haemolytic disease due to ABO
      incompatibility is recommended by the American Academy of Pediatrics and the
      National Blood Authority, Australia. However, the evidence these recommendations
      are based on appears limited and, in some instances, outdated. In our article, we
      review the current available literature to help answer the question, 'In infants
      with isoimmune haemolytic disease due to ABO incompatibility [P], does use of
      intravenous immunoglobulin and intensive phototherapy [I] compared with intensive
      phototherapy alone [C] provide any clinically important benefits [O]?' 

PMID- 24325717
TI  - Pyrexia of unknown origin. Tuberculin skin test (TST); induration 26 mm diameter.

PMID- 24325722
TI  - TLR2 and TLR4 in healthy children: age and gender differences.

PMID- 24325723
TI  - Mobile phones as a potential vector of infection in a paediatric ward.

PMID- 24325724
TI  - Poractant alfa versus beractant in the treatment of preterm infants with
      respiratory distress syndrome.

PMID- 24325727
TI  - Ultrasound presentation of abdominal tuberculosis in a German tertiary care
      center.
AB  - OBJECTIVE: Abdominal tuberculosis (TB) is a relatively rare disease in most of
      Europe and the typical clinical and sonographic findings in this setting have not
      been studied. We aimed to define sonographic findings that should alert an
      examiner to the possibility of abdominal TB in a low endemic region. METHODS:
      Case records of 17 patients with proven (n = 11) or highly likely (n = 6)
      abdominal TB detected in the gastrointestinal ultrasound unit at a German
      tertiary care center in 2003-2013 were analyzed retrospectively. Findings were
      compared with reported series from high-prevalence regions. RESULTS: While 76% of
      patients had an immigrant background, only 35% had a condition associated with
      immunosuppression. Lymphadenopathy was present in all cases of abdominal TB,
      while it was absent in 28% of patients from a control group with proven abdominal
      sarcoidosis. Moreover, retroperitoneal lymphadenopathy was significantly more
      common in TB. Other findings in patients with abdominal TB in descending order of
      frequency were ascites, altered hepatic texture, splenomegaly, splenic lesions,
      peritoneal thickening, intestinal wall lesions, hepatic lesions and hepatomegaly.
      76% of abdominal TB patients had 2 or more pathological findings. CONCLUSIONS:
      Multiple pathological intra-abdominal findings including lymphadenopathy should
      alert the examiner to the possibility of abdominal TB.

PMID- 24325728
TI  - MmpL3 a potential new target for development of novel anti-tuberculosis drugs.
AB  - INTRODUCTION: Tuberculosis (TB) is still a leading cause of mortality in the
      developing world and there is an unmet clinical need for new drugs with novel
      mechanism of action. Targeting the complex and unique cell wall of TB-causing
      pathogen Mycobacterium tuberculosis (Mtb) has been a mainstay of TB drug
      discovery. Though, the composition of the cell wall of Mtb is well understood,
      little is known about the assembly process of the cell wall such as the transport
      of mycolic acids across the cell wall. AREAS COVERED: Recent research
      demonstrating MmpL3 protein as a transmembrane transporter of mycolic acids is
      discussed. In addition, MmpL3 has also been implicated in heme transport.
      Research describing several diverse chemical inhibitors that inhibit MmpL3 is
      reviewed. EXPERT OPINION: Evidence so far suggests MmpL3 is a transporter of
      mycolic acids. It has emerged as a novel therapeutic target for Mtb that is
      essential and for which several small molecule inhibitors have been identified.
      Identifying the interacting partners, understanding the substrate specificity and
      the mechanism of transport by MmpL3 are some of the gaps in knowledge that need
      to be addressed.

PMID- 24325729
TI  - Lactation accommodation in the workplace and duration of exclusive breastfeeding.
AB  - INTRODUCTION: The purpose of this study was to assess current lactation
      accommodations in a workplace environment and to examine the association between
      the different dimensions of support and the duration of exclusive breastfeeding.
      METHODS: A survey was conducted with employees of a higher-education institution
      and clients of an obstetric hospital in New Jersey. Factor analysis identified
      dimensions of workplace support. The dimensions were correlated with the duration
      of exclusive breastfeeding using Pearson's r correlation analysis. RESULTS: One
      hundred and thirteen working mothers participated in the study. The mean (SD)
      number of working hours of the participants was 34.3 (2.8) hours per week.
      Participants were primarily white (89.4%), older (mean age, 33.8 [6.0] years),
      highly educated (>82% above college graduate), and married (92%). Participants
      indicated that in their workplaces, breastfeeding was not common, breast pumps
      were not available, and on-site day care was not always an option. The analysis
      identified 4 dimensions of breastfeeding accommodation: break time, workplace
      environment, technical support, and workplace policy. Technical support (r =
      0.71, P = .01) and workplace environment (r = 0.26, P = .01) were significantly
      associated with the duration of exclusive breastfeeding. DISCUSSION: Employers
      can strengthen technical support and workplace environment to encourage
      breastfeeding continuation in working mothers. New federal laws should consider
      specific guidelines for minimum requirements for functional lactation support to
      achieve comprehensive breastfeeding benefits.

PMID- 24325730
TI  - MOVE: weight management program across the Veterans Health Administration:
      patient- and facility-level predictors of utilization.
AB  - BACKGROUND: Health care systems initiating major behavioral health programs often
      face challenges with variable implementation and uneven patient engagement. One
      large health care system, Veterans Health Administration (VHA), recently
      initiated the MOVE!(r) Weight Management Program, but it is unclear if veterans
      most in need of MOVE!(r) services are accessing them. The purpose of this study
      was to examine patient and facility factors associated with MOVE!(r) utilization
      (defined as 1 or more visits) across all VHA facilities. METHODS: Using national
      administrative data in a retrospective cohort study of eligible overweight (25 <
      = body mass index (BMI) < 30 and at least one obesity associated comorbidity) and
      obese (BMI > =30) VHA outpatients, we examined variation in and predictors of
      MOVE!(r) utilization in fiscal year (FY) 2010 using generalized linear mixed
      models. RESULTS: 4.39% (n = 90,230) of all eligible overweight and obese patients
      using VHA services utilized MOVE!(r) services at least once in FY 2010. Facility
      level MOVE! Utilization rates ranged from 0.05% to 16%. Veterans were more likely
      to have at least one MOVE!(r) visit if they had a higher BMI, were female,
      unmarried, younger, a minority, or had a psychiatric or obesity-related
      comorbidity. CONCLUSIONS: Although substantial variation exists across VHA
      facilities in MOVE!(r) utilization rates, Veterans most in need of obesity
      management services were more likely to access MOVE!(r), although at a low level.
      However, there may still be many Veterans who might benefit but are not accessing
      these services. More research is needed to examine the barriers and facilitators
      of MOVE!(r) utilization, particularly in facilities with unusually high and low
      reach.

PMID- 24325731
TI  - Treatment of porcine donor cells and reconstructed embryos with the antioxidant
      melatonin enhances cloning efficiency.
AB  - This study was conducted to investigate the effect of melatonin during the
      culture of donor cells and cloned embryos on the in vitro developmental
      competence and quality of cloned porcine embryos. At concentrations of 10(-6 )M
      or 10(-8) M, melatonin significantly enhanced the proliferation of porcine fetal
      fibroblasts (PFFs), and the blastocyst rate was significantly increased in the
      10(-10) M melatonin-treated donor cell group. Cloned embryo development was also
      improved in embryo culture medium that was supplemented with 10(-9) M or 10(-12)
      M melatonin. When both donor cells and cloned embryos were treated with
      melatonin, the cleavage rate and total cell number of blastocysts were not
      significantly affected; however, the blastocyst rate was increased significantly
      (20.0% versus 11.7%). TUNEL assays showed that combined melatonin treatment
      reduced the rate of apoptotic nuclei (3.6% versus 6.1%). Gene expression analysis
      of the apoptosis-related genes BAX, BCL2L1, and p53 showed that the expression of
      BCL2L1 was significantly elevated 2.7-fold relative to the control group, while
      the expression of BAX and p53 was significantly decreased by 3.7-fold and 23.2
      fold, respectively. In addition, we detected the expression of two melatonin
      receptors (MT1 and MT2) in PFFs but not in porcine cloned embryos. We conclude
      that exogenous melatonin enhances the development of porcine cloned embryos and
      improves embryo quality by inhibiting p53-mediated apoptotic pathway. The
      proliferation of PFFs may be mediated by receptor binding, but the beneficial
      effects of melatonin on embryonic development may be receptor-independent,
      possibly through melatonin's ability to directly scavenge free radicals.

PMID- 24325732
TI  - Highly selective inhibition of butyrylcholinesterase by a novel melatonin-tacrine
      heterodimers.
AB  - Novel inhibitors of cholinesterases, especially butyrylcholinesterase (BuChE),
      were obtained by coupling melatonin-tacrine heterodimers via the carbamate bond.
      Compounds 14a-i possessed potent cholinesterase inhibitory activity (with IC50
      values as low as 1.18 nM for acetylcholinesterase (AChE) and 0.24 nM for
      butyrylcholinesterase (BuChE)). These heterodimers exhibit selectivity toward
      BuChE, being from 4- to 256-fold more active toward BuChE than AChE, but still
      acting as better AChE inhibitors than tacrine 4.

PMID- 24325733
TI  - CREBZF expression and hormonal regulation in the mouse uterus.
AB  - BACKGROUND: CREBZF is a member of the mammalian ATF/CREB family of the basic
      region-leucine zipper (bZIP) transcription factors. Two isoforms of CREBZF have
      been identified from the alternative usage of initiation codons, SMILE (long
      isoform of CREBZF) and Zhangfei (short isoform of CREBZF). Until recently, the
      physiological function of CREBZF in mammalian reproductions has not been
      reported. METHODS: Multiple techniques were performed to investigate the
      spatiotemporal expression and hormonal regulation of the CREBZF gene in the mouse
      uterus and its role in embryo implantation. RESULTS: Zhangfei was not detected in
      the mouse uterus. SMILE immunostaining was mainly expressed in the uterine
      luminal and glandular epithelium, and the expression levels of both SMILE mRNA
      and protein gradually decreased from days 1-3 of pregnancy, peaked on day 4, and
      then declined again on day 6. On day 5 of pregnancy, SMILE protein expression was
      detected only in the luminal epithelium at implantation sites compared with the
      expression at inter-implantation sites. SMILE protein was not detected in
      decidual cells from days 6-8 of pregnancy or artificial decidualisation.
      Furthermore, SMILE protein was not detected in the mouse uterus on days 3-6 of
      pseudopregnancy, and SMILE expression was also induced in the delayed
      implantation uterus, indicating that the presence of an active blastocyst was
      required for SMILE expression at the implantation site. Oestrogen significantly
      stimulated SMILE expression in the ovariectomised mouse uterus. In addition, in
      cycling mice, high levels of SMILE protein and mRNA expression were also observed
      in proestrus and oestrus uteri. CONCLUSIONS: Taken together, these results
      suggested that SMILE expression was closely related to mouse implantation and up
      regulated by oestrogen.

PMID- 24325734
TI  - A biomimetic copper water oxidation catalyst with low overpotential.
AB  - Simply mixing a Cu(II) salt and 6,6'-dihydroxy-2,2'-bipyridine (H2L) in a basic
      aqueous solution afforded a highly active water oxidation catalyst (WOC). Cyclic
      voltammetry of the solution at pH = 12-14 shows irreversible catalytic current
      with an onset potential of ~0.8 V versus NHE. Catalytic oxygen evolution takes
      place in controlled potential electrolysis at a relatively low overpotential of
      640 mV. Experimental and computational studies suggest that the L ligand
      participates in electron transfer processes to facilitate the oxidation of the Cu
      center to lead to an active WOC with low overpotential, akin to the use of the
      tyrosine radical by Photosystem II to oxidize the CaMn4 center for water
      oxidation.

PMID- 24325735
TI  - Early detection of colon cancer by amino acid profiling using AminoIndex
      Technology: a case report.
AB  - Most tumor markers have low detection rates for curable stages of cancer and are
      therefore not satisfactory for use in a healthy population. A new cancer risk
      calculation method, AminoIndex Cancer Screening (AICS), uses multiple plasma
      amino acid concentrations to calculate the risks for several cancers
      simultaneously and is suggested to have a high detection rate for early-stage
      cancers and a low false-positive rate for adenomas. Here, we describe a male
      patient with a family history of colorectal cancer who underwent AICS. He was
      judged as Rank C for colorectal cancer, which reportedly has a specificity of
      95%, a sensitivity of 41%, and an estimated positive predictive value of 0.67%.
      He underwent colonoscopy for a secondary screening, which revealed a 10-mm
      adenoma-like lesion in the ascending colon, with a biopsy report of partial
      carcinoma. The tumor was endoscopically removed and diagnosed as carcinoma in
      situ (carcinoma in adenoma). This early detection method allowed complete
      resection of the carcinoma, and the patient is in remission. This is the first
      case in which a curable cancer was detected using AICS. With its high detection
      rate for early-stage cancers and its ease of use, this tool, which recently
      became available in Japan, may be beneficial for simultaneous screening of the
      general population for multiple cancers. Virtual slides: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2145080259887842.

PMID- 24325736
TI  - Ethnic and gender susceptibility to metabolic risk.
AB  - BACKGROUND: Aggregation of metabolic risk factors-i.e., elevated plasma
      triglyceride (TG), reduced high-density lipoprotein cholesterol (HDL-C), elevated
      blood pressure, and raised plasma glucose-convey increased risk for
      atherosclerotic cardiovascular disease and type 2 diabetes. METHODS: This study
      was carried out to determine the association of waist girth, ethnicity, and
      gender with susceptibility for metabolic risk. Included were 1671 adult women
      (50.7% black) and 1339 men (46.5% black) enrolled in the Dallas Heart Study.
      Subjects were stratified into three categories by waist girth-low, intermediate,
      and high, corresponding to BMI ranges of <25 kg/m(2), 25-29.9 kg/m(2), and >=30
      kg/m(2). RESULTS: Risk factor prevalence rose progressively through each waist
      girth category. However, even among those with high waist-girth, prevalence of
      three or more risk factors was less than 50%. Several differences among the
      ethnic groups were noted; for example, Hispanic men had a higher prevalence of
      elevated TG compared to whites; black men, on the other hand, had a lower
      frequency of high TG. There were also fewer black men with low HDL-C than in the
      other groups. Black and Hispanic men had a higher prevalence of elevated glucose
      and updated homeostasis model assessment of insulin resistance (HOMA2-IR) than
      whites. More black men had elevated blood pressure than other groups. These
      differences were less pronounced among ethnic groups of women. CONCLUSION:
      Although ethnic and gender differences in risk factor prevalence may exist, it is
      notable that the majority of subjects, even when obese, did not have elevated
      risk factors. This finding points to the need to focus largely on subjects with
      metabolic risk factors when implementing therapeutic interventions.

PMID- 24325738
TI  - Interactions between drugs and polymers influencing hot melt extrusion.
AB  - OBJECTIVES: Hot melt extrusion (HME) as a technique for producing amorphous solid
      dispersion (ASD) has been widely used in pharmaceutical research. The biggest
      challenge for the application of HME is the thermal degradation of drug, poor
      physical stability of ASD and precipitation of drug during dissolution.
      Interactions between drugs and polymers may play an important role in overcoming
      these barriers. In this review, influence of drug-polymer interactions on HME and
      the methods for characterizing the drug-polymer interactions were reviewed. KEY
      FINDINGS: Strong drug-polymer interactions, especially ionic interactions and
      hydrogen bonds, are helpful to improving the thermal stability of drug during
      HME, enhancing the physical stability of ASD during storage and maintaining
      supersaturated solution after dissolution in gastrointestinal tract. The
      interactions can be quantitatively and qualitatively characterized by many
      analysing methods. CONCLUSIONS: As many factors collectively determine the
      properties of HME products, drug-polymer interactions play an extremely important
      role. However, the action mechanisms of drug-polymer interactions need intensive
      investigation to provide more useful information for optimizing the formulation
      and the process parameters of HME.

PMID- 24325739
TI  - Side population cell fractions from hepatocellular carcinoma cell lines increased
      with tumor dedifferentiation, but lack characteristic features of cancer stem
      cells.
AB  - BACKGROUND AND AIM: Cancer stem cells (CSCs), a minority population with stem
      cell-like characteristics, play important roles in cancer development and
      progression. Putative CSC markers, such as CD13, CD90, CD133, and epithelial cell
      adhesion molecule (EpCAM), and side population (SP) technique are generally used
      in an attempt to isolate CSCs. We aimed to clarify the relationship between CSCs
      and clonal dedifferentiation in hepatocellular carcinoma (HCC). METHODS: We used
      a well-differentiated HCC cell line (HAK-1A) and a poorly differentiated HCC cell
      line (HAK-1B) established from a single nodule with histological heterogeneity.
      HAK-1B arose because of clonal dedifferentiation of HAK-1A. The SP cells and non
      SP (NSP) cells were isolated from the two cell lines with a FACSAria II and used
      for the analyses. RESULTS: The SP cell fractions in HAK-1A and HAK-1B were 0.2%
      and 0.9%, respectively. CD90 or EpCAM was not expressed in either HAK-1A or HAK
      1B, while CD13 and CD133 were expressed in HAK-1B alone. Although sphere forming
      ability, tumorigenicity, growth rate, and CD13 expression were higher in HAK-1B
      SP cells than HAK-1B NSP cells, there were no differences in drug resistance,
      colony forming ability, or cell cycle rates between HAK-1B SP and NSP cells,
      suggesting HAK-1B SP cells do not fulfill CSC criteria. CONCLUSIONS: Our findings
      suggested a possible relationship between the expression of CSC markers and
      clonal dedifferentiation. However, the complete features of CSC could not be
      identified in SP cells, and the concept of SP cells as a universal marker for CSC
      may not apply to HAK-1A and HAK-1B.

PMID- 24325740
TI  - The genetics of vascular incidents associated with second-generation
      antipsychotic administration.
AB  - Second-generation antipsychotics (SGA) have been associated with risk of stroke
      in elderly patients, but the molecular and genetic background under this
      association has been poorly investigated. The aim of the present study was to
      prioritize a list of genes with an SGA altered expression in order to
      characterize the genetic background of the SGA-associated stroke risk. Genes with
      evidence of an altered expression after SGA treatments in genome-wide
      investigations, both in animals and men, were identified. The Genetic Association
      Database (GAD) served to verify which of these genes had a proven positive
      association with an increased stroke risk, and along with it each evidence was
      tested and recorded. Seven hundred and forty five genes had evidence of a change
      of their expression profile after SGA administration in various studies. Nine out
      of them have also been significantly related to an increased strokes risk. We
      identified and described nine genes as potential candidates for future genetic
      studies aimed at identifying the genetic background of the SGA-related stroke
      risk. Further, we identify the molecular pathways in which these genes operate in
      order to provide a molecular framework to understand on which basis SGA may
      enhance the risk for stroke.

PMID- 24325737
TI  - HIV-exposed uninfected children: a growing population with a vulnerable immune
      system?
AB  - Through the successful implementation of policies to prevent mother-to-child
      transmission (PMTCT) of HIV-1 infection, children born to HIV-1-infected mothers
      are now much less likely to acquire HIV-1 infection than previously.
      Nevertheless, HIV-1-exposed uninfected (HEU) children have substantially
      increased morbidity and mortality compared with children born to uninfected
      mothers (unexposed uninfected, UU), predominantly from infectious causes.
      Moreover, a range of phenotypical and functional immunological differences
      between HEU and UU children has been reported. As the number of HEU children
      continues to increase worldwide, two questions with clear public health
      importance need to be addressed: first, does exposure to HIV-1 and/or ART in
      utero or during infancy have direct immunological consequences, or are these poor
      outcomes simply attributable to the obvious disadvantages of being born into an
      HIV-affected household? Secondly, can we expect improved maternal care and ART
      regimens during and after pregnancy, together with optimized infant immunization
      schedules, to reduce the excess morbidity and mortality of HEU children? 

PMID- 24325741
TI  - Exposure science comes of age.

PMID- 24325742
TI  - 21st century exposure: an opposing view.

PMID- 24325743
TI  - Determinants of metals exposure to metalworking fluid among metalworkers in
      Taiwan.
AB  - Metalworking fluids (MWFs) aerosols are known to have carcinogenic potential to
      humans that monitoring of MWFs is necessary to reduce risks. This study
      summarizes biological monitoring and occupational hygiene findings from a survey
      of metalworkers exposed to heavy metals in a socket manufacturing plant.
      Manganese, nickel, iron, copper, chromium, and zinc were selected for target
      metals. Air samples were collected and postshift urines were obtained from the
      thread cutting workers and punch press machine operators. There were positive
      correlations between the airborne concentrations of Cr, Mn, as well as Zn and the
      corresponding levels of urine for the exposed groups. Therefore, the integration
      of biological and environmental monitoring is feasible for Cr, Mn, and Zn. The
      results indicated significant correlations between the levels of Cu, Cr, Fe, as
      well as Zn from the air and sump MWFs at thread cutting and punch press sites.

PMID- 24325744
TI  - Risk of non-Hodgkin's lymphoma and residential exposure to air pollution in an
      industrial area in northern Italy: a case-control study.
AB  - The aim of this study was to evaluate the risk of non-Hodgkin's lymphoma (NHL) in
      an adult population residing in an area in northern Italy exposed to industrial
      air pollution from a big power plant, a coke oven, 2 chemical factories, and some
      minor plants. The design was a population-based case-control study and
      information about residential history and the main risk factors for NHL was
      obtained interviewing 133 cases and 279 controls using a structured
      questionnaire. Three exposure categories (heavy, moderate, and slight) were
      defined on the basis of the location of the major facilities with respect to the
      subject residence. NHL risk was not associated either with location or duration
      of residence in the heavily polluted area. However, the unavoidable limitations
      of this study prevent us from drawing definitive conclusions.

PMID- 24325745
TI  - Association of surface contamination by antineoplastic drugs with different
      working conditions in hospital pharmacies.
AB  - This study investigates the surface contamination levels of cyclophosphamide and
      platinum (a marker of platinum-containing drugs) in storage and preparation areas
      of hospital pharmacies and their relationship to working conditions surveyed by
      questionnaire. In total, 259 wipe samples were collected in 13 hospital
      pharmacies over 4 sampling campaigns. After sample extraction with acetate
      buffer, cyclophosphamide and platinum were determined using high-performance
      liquid chromatography-tandem mass spectroscopy (HPLC-MS/MS) and inductively
      coupled plasma mass spectrometry (ICP-MS). Depending on the sampling spot and
      campaign, median concentrations ranged from <2 to 61 pg/cm(2) and from <0.2 to
      6.9 pg/cm(2) for cyclophosphamide and platinum, respectively. Statistical
      evaluation of monitoring data revealed that the contamination level was
      significantly influenced by laboratory throughput (expressed as number of
      chemotherapies prepared per week), personnel expertise (ie, participation of
      pharmacists with academic education in drug admixture activities), and surface
      material.

PMID- 24325746
TI  - Relationship of burnout with personality, alexithymia, and coping behaviors among
      physicians in a semiurban and rural area in Turkey.
AB  - This present study aimed to assess levels of burnout, to investigate the extent
      to which personal characteristics and coping behaviors are related to burnout,
      and to establish the predictors of burnout among physicians in a semiurban and
      rural area. A sample of 139 physicians was assessed using the Maslach Burnout
      Inventory, Eysenck Personality Questionnaire, Toronto Alexithymia Scale, and Ways
      of Coping Inventory. The level of burnout was found to be moderately higher than
      those reported among urban physicians. A forward stepwise multiple regression
      analysis indicated that neuroticism, occupation (specialist vs general
      practitioner), helpless, self-confident, and social support seeking approaches
      were predictors of burnout. The results showed that burnout was negatively
      related with problem-focused copping strategies, and positively with emotion
      focused coping strategies. Fostering problem-focused coping strategies in
      physicians might be useful in the reduction of burnout.

PMID- 24325747
TI  - Occupational cancer risk perception in Iranian workers.
AB  - This cross-sectional study examined the occupational cancer risk perception among
      269 Iranian industrial workers according to their knowledge, job titles hazard,
      and demographical properties. The structured questionnaire was used to measure
      participants' knowledge and perception toward occupational cancers (reliability
      of the perception questions = .72). There was significant difference in both
      knowledge and perception about occupational cancers in different age and
      educational groups. It was significant relation between knowledge and perception
      (p = .001). True answer to some questions was less than 20%. An optimistic bias
      was found in participants' perception. These findings prove that cancer risk
      perception in industrial workforces is affected by several factors. Further
      efforts should be placed in the training of workers to enhance their knowledge
      and subsequently their perception toward occupational cancers.

PMID- 24325748
TI  - The association between occupational exposures and cigarette smoking among
      operating engineers.
AB  - The purpose of this study was to determine the relationship between occupational
      exposures and cigarette smoking among operating engineers. A cross-sectional
      survey was conducted with operating engineers (N = 412) from a midwestern state
      in the United States. The survey included validated questions on cigarette
      smoking, occupational exposures, demographics, comorbidities, and health
      behaviors. About 35% were current smokers. Those exposed to asphalt fumes, heat
      stress, concrete dust, and welding fumes were less likely to smoke (odds ratio
      [OR] = .79, 95% confidence interval [CI]: .64-.98). Other factors associated with
      smoking included younger age (OR = .97, 95% CI: .94-.99), problem drinking (OR =
      1.07, 95% CI: 1.03-1.12), lower Body Mass Index (OR = .95, 95% CI: .90-.99), and
      being separated/widowed/divorced (OR = 2.24, 95% CI: 1.19-4.20). Further
      investigation is needed for better understanding about job-specific exposure
      patterns and their impact on cigarette smoking among operating engineers.

PMID- 24325749
TI  - 8-hydroxydeoxyguanosine as a useful marker for determining the severity of
      trichloroethylene exposure.
AB  - The aim of this study was to determine 8-hydroxydeoxyguanosine (8-OH-dG) levels
      in trichloroethylene (TCE)-exposed workers. Oxidative stress biomarkers and
      biochemical parameters were monitored among 26 TCE-exposed workers and 78 age
      matched control subjects. Levels of urinary 8-OH-dG were analyzed by liquid
      chromatography tandem mass spectrometry. Urinary 8-OH-dG levels were
      significantly higher for TCE-exposed group (p < .001). Spearman's correlation
      test revealed positive correlations between urinary trichloroacetic acid levels
      and age, urinary 8-OH-dG, urinary total oxidant status, and urinary total
      antioxidant status (p = .042, p < .001, p < .001, and p < .001, respectively). 8
      OH-dG may be a useful marker to determine the extent of TCE exposure.

PMID- 24325751
TI  - Below-band-gap ionization of liquid-to-supercritical ammonia: geminate
      recombination via proton-coupled back electron transfer.
AB  - Femtosecond multiphoton ionization experiments have been conducted on ammonia
      over a wide range of temperature (225 K <= T <= 490 K) and density (0.18 g/cm(3)
      <= rho <= 0.7 g/cm(3)), thereby covering the liquid and supercritical phases. The
      experiments were carried out with excitation pulses having a wavelength of 400
      nm, and the ionization was found to involve two photons. Therefore, the total
      ionization energy in this study corresponds to 6.2 eV, which is roughly 2 eV
      below the valence-to-conduction band gap of the fluid. The ionization generates
      solvated electrons, which have been detected through their characteristic near
      infrared resonance, and must be facilitated through a coupling to nuclear degrees
      of freedom of the liquid. The recombination of the solvated electron with the
      geminate fragments was found to obey predominantly single-exponential kinetics
      with time constants between 500 fs and 1 ps. Only a very minor fraction of the
      photogenerated electrons is able to escape from the geminate recombination. The
      results indicate that the majority of electrons are injected into suitable
      trapping sites located between the first and second solvation shells of the
      initially ionized ammonia molecules. Such configurations can be considered as
      instantly reactive and facilitate an ultrafast barrierless electron annihilation.
      This process is found to exhibit a pronounced kinetic isotope effect, which
      indicates that the electronic decay is accompanied by the transfer of a proton.
      The sequence of ionization and recombination events can therefore be described
      appropriately as a proton-coupled electron transfer (PCET) followed by a proton
      coupled back electron transfer (PCBET). 

PMID- 24325752
TI  - Effectiveness of a Mindfulness-Based Childbirth Education pilot study on maternal
      self-efficacy and fear of childbirth.
AB  - INTRODUCTION: This pilot study tested the feasibility and effectiveness of using
      Mindfulness-Based Childbirth Education (MBCE), a novel integration of mindfulness
      meditation and skills-based childbirth education, for mental health promotion
      with pregnant women. The MBCE protocol aimed to reduce fear of birth, anxiety,
      and stress and improve maternal self-efficacy. This pilot study also aimed to
      determine the acceptability and feasibility of the MBCE protocol. METHODS: A
      single-arm pilot study of the MBCE intervention using a repeated-measures design
      was used to analyze data before and after the MBCE intervention to determine
      change trends with key outcome variables: mindfulness; depression, anxiety, and
      stress; childbirth self-efficacy; and fear of childbirth. Pregnant women (18-28
      weeks' gestation) and their support companions attended weekly MBCE group
      sessions over 8 weeks in an Australian community setting. RESULTS: Of the 18
      women who began and completed the intervention, missing data allowed for complete
      data from 12 participants to be analyzed. Statistically significant improvements
      and large effect sizes were observed for childbirth self-efficacy and fear of
      childbirth. Improvements in depression, mindfulness, and birth outcome
      expectations were underpowered. At postnatal follow-up significant improvements
      were found in anxiety, whereas improvements in mindfulness, stress, and fear of
      birth were significant at a less conservative alpha level. DISCUSSION: This pilot
      study demonstrated that a blended mindfulness and skills-based childbirth
      education intervention was acceptable to women and was associated with
      improvements in women's sense of control and confidence in giving birth. Previous
      findings that low self-efficacy and high childbirth fear are linked to greater
      labor pain, stress reactivity, and trauma suggest the observed improvements in
      these variables have important implications for improving maternal mental health
      and associated child health outcomes. Ways in which these outcomes can be
      achieved through improved childbirth education are discussed.

PMID- 24325753
TI  - Expression of Cox-2 in human breast cancer cells as a critical determinant of
      epithelial-to-mesenchymal transition and invasiveness.
AB  - INTRODUCTION: Cyclooxygenase-2 (COX-2) is overexpressed in several malignancies
      and is implicated in breast cancer progression. OBJECTIVES: We investigated
      whether changes in COX-2 expression may affect epithelial-to-mesenchymal
      transition (EMT) and then invasive potential of human breast cancer cells, in
      relationship with hypoxia. COX-2-null MCF-7 human breast cancer cells, MCF-7
      cells transiently expressing COX-2 and COX-2-expressing MDA-MB-231 cells were
      employed. RESULTS: COX-2 overexpression resulted in downregulation of E-cadherin
      and beta-catenin, upregulation of vimentin, N-cadherin and SNAI1, suggesting EMT
      occurrence. COX-2-overexpressing MCF-7 cells were also characterized by increased
      invasiveness and release of matrix-metalloproteinase-9. The above-mentioned
      characteristics, homologous to those detected in highly invasive MDA-MB-231
      cells, were reverted by treatment of COX-2-overexpressing MCF-7 cells with
      celecoxib, a COX-2-specific inhibitor, partly through the inhibition of COX-2
      related intracellular generation of reactive oxygen species. Hypoxia further
      exacerbated COX-2 expression, EMT changes and invasive ability in both COX-2
      overexpressing MCF-7 cells and MDA-MB-231 cells. Finally, immunohistochemistry
      performed on samples from normal and neoplastic human breast tissues revealed
      that COX-2-positive malignant cells were also positive for EMT-related antigens,
      hypoxia-inducible factor (HIF)-2alpha and the oxidative stress marker heme
      oxygenase. CONCLUSIONS: These findings support the existence of a direct link
      between COX-2 overexpression, EMT and invasiveness in human breast cancer cells,
      emphasizing the role of hypoxic microenvironment.

PMID- 24325755
TI  - Critical evaluation of the two-state model describing the equilibrium unfolding
      of the PI3K SH3 domain by time-resolved fluorescence resonance energy transfer.
AB  - It appears that equilibrium unfolding transitions of many small proteins can be
      described as two-state transitions, because the probes commonly used to measure
      such transitions cannot detect the underlying heterogeneity inherent in protein
      folding and unfolding reactions. Time-resolved fluorescence or Forster resonance
      energy transfer (TRFRET) measurements have the potential to uncover such
      heterogeneity and to test the cooperativity of protein folding reactions. Here,
      TRFRET measurements have been used to study the equilibrium unfolding of the SH3
      domain of PI3 kinase. The single tryptophan residue (W53) was used as the FRET
      donor, and a covalently attached thionitrobenzoate moiety at either of two sites
      (C17 and C70) was used as the FRET acceptor. The individual lifetime and
      amplitude components estimated from fitting the fluorescence decay kinetics to
      the sum of three or four exponentials were determined over a range of denaturant
      concentrations. The equilibrium unfolding transitions reported by these
      components were found to be noncoincident, suggesting the presence of multiple
      conformations in equilibrium during the course of unfolding. Fluorescence
      lifetime distributions were also generated by the model-free maximum entropy
      method of analysis. Different segments of the protein were found to show
      differences in the expansion of the native state at low denaturant
      concentrations, suggestive of gradual structural transitions. The unfolded
      protein was found to swell at increasingly high denaturant concentrations. The
      evolution of the fluorescence lifetime distributions with increasing denaturant
      concentration was also found to be incompatible with a two-state equilibrium
      unfolding model. 

PMID- 24325754
TI  - Effect of pH on in vitro biocompatibility of orthodontic miniscrew implants.
AB  - BACKGROUND: Although the clinical use of miniscrews has been investigated on a
      large scale, little is known about their biocompatibility. Since low pH can
      affect corrosion resistance, the aim of this study was to evaluate the cytotoxic
      effect of orthodontic miniscrews in different pH conditions. METHODS: Four
      orthodontic miniscrews of stainless steel and grade IV and grade V titanium were
      immersed in a pH 7 and pH 4 saline solution for 1, 7, 14, 21, 28, and 84 days.
      Human osteogenic sarcoma cells (U2OS), permanent human keratinocytes (HaCat), and
      primary human gingival fibroblasts (HGF) were exposed to eluates, and the
      mitochondrial dehydrogenase activity was measured after 24 h to assess the
      cytoxicity. The results were analyzed using the Mann-Whitney U test (P<0.05).
      RESULTS: When exposed to pH 7-conditioned eluates, the cell lines showed an even
      greater viability than untreated cells. On the contrary, the results revealed a
      statistically significant decrease in U2OS, HaCat, and HGF viability after
      exposure to eluates obtained at pH 4. Among the cell lines tested, HGF showed the
      most significant decrease of mitochondrial activity. Interestingly, grade V
      titanium miniscrews caused highest toxic effects when immersed at pH 4.
      CONCLUSIONS: The results suggested that at pH 7, all the miniscrews are
      biocompatible while the eluates obtained at pH 4 showed significant cytotoxicity
      response. Moreover, different cell lines can produce different responses to
      miniscrew eluates.

PMID- 24325756
TI  - Comparison between thromboelastography and conventional coagulation tests after
      cardiopulmonary bypass surgery in the paediatric intensive care unit.
AB  - INTRODUCTION: Following paediatric cardiac surgery using cardiopulmonary bypass
      (CPB), there is a risk of significant postoperative bleeding. A number of risk
      factors are associated with postoperative bleeding including; age, complexity of
      the surgery, dilution and consumption of clotting factors. We conducted a
      prospective audit comparing different coagulation tests used following paediatric
      CPB to determine whether thromboelastography (TEG) on the intensive care unit or
      routine laboratory coagulation assays including fibrinogen are better at
      assessing bleeding and bleeding risk. METHODS: Tests on arrival in paediatric
      intensive care unit (PICU) included the following: fibrinogen, prothrombin time,
      activated partial thromboplastin time, full blood count and TEG. Bleeding was
      measured in the first 1-4 h via chest drain loss. Bleeding was considered
      significant if >=5 ml/kg/h. RESULTS: Of 107 patients admitted to PICU, 23/107
      were considered to be bleeding during the first hour. Fibrinogen concentration
      had the best correlation with the amount of first-hour blood loss (r(s) = 0.52),
      followed by APTT (r(s) = 0.44) and TEG MA (r(s) = 0.34). TEG parameter TEG MA
      correlated with platelet count (r(s) = 0.68) and fibrinogen (r(s) = 0.66).
      CONCLUSIONS: Thromboelastography did not show better correlation with
      postoperative bleeding than conventional clotting tests. TEG parameter maximum
      amplitude correlates with platelet count and fibrinogen.

PMID- 24325757
TI  - Validity of 2D lateral cephalometry in orthodontics: a systematic review.
AB  - Lateral cephalometric radiography is commonly used as a standard tool in
      orthodontic assessment and treatment planning. The aim of this study was to
      evaluate the available scientific literature and existing evidence for the
      validation of using lateral cephalometric imaging for orthodontic treatment
      planning. The secondary objective was to determine the accuracy and reliability
      of this technique. We did not attempt to evaluate the value of this radiographic
      technique for other purposes. A literature search was performed using specific
      keywords on electronic databases: Ovid MEDLINE, Scopus and Web of Science. Two
      reviewers selected relevant articles, corresponding to predetermined inclusion
      criteria. The electronic search was followed by a hand search of the reference
      lists of relevant papers. Two reviewers assessed the level of evidence of
      relevant publications as high, moderate or low. Based on this, the evidence grade
      for diagnostic efficacy was rated as strong, moderately strong, limited or
      insufficient. The initial search revealed 784 articles listed in MEDLINE (Ovid),
      1,034 in Scopus and 264 articles in the Web of Science. Only 17 articles met the
      inclusion criteria and were selected for qualitative synthesis. Results showed
      seven studies on the role of cephalometry in orthodontic treatment planning,
      eight concerning cephalometric measurements and landmark identification and two
      on cephalometric analysis. It is surprising that, notwithstanding the 968
      articles published in peer-reviewed journals, scientific evidence on the
      usefulness of this radiographic technique in orthodontics is still lacking, with
      contradictory results. More rigorous research on a larger study population should
      be performed to achieve full evidence on this topic. 

PMID- 24325759
TI  - Combined usage of intercostal nerve block and tumescent anaesthesia: an effective
      anaesthesia technique for breast augmentation.
AB  - Patients are occasionally unhappy with the size, shape, and positioning of breast
      implants. An option to improve their satisfaction with breast augmentation
      includes directly involving them in the process with awake surgery done under
      nerve block and tumescence. This study describes the resultsof using such an
      awake anaesthesia technique in 35 patients. After the intercostal nerves
      dominating the Th3 to Th6 regions were anaesthetized using 0.5% bupivacaine, a
      tumescent solution consisting of lidocaine, epinephrine, and saline was injected
      around the mammary gland, and breast augmentation was conducted using silicon
      implants. The majority of patients (31/35) reported no pain during the procedure
      and all patients were able to choose and confirm their final implant size and
      positioning. In all cases, blood loss was less than 10 ml. No patient experienced
      pneumothorax or toxicity of local anaesthetics. Combined usage of the intercostal
      nerve block and tumescent anaesthesia effectively reduces pain during breast
      augmentation. Keeping patient conscious enables meeting their requests during
      operation, contributing to increased satisfaction. For these advantages, combined
      usage of the intercostal nerve block and tumescent anaesthesia is recommended as
      a useful anaesthetic technique for breast augmentation.

PMID- 24325758
TI  - Effect of chlorhexidine-containing prophylactic agent on the surface
      characterization and frictional resistance between orthodontic brackets and
      archwires: an in vitro study.
AB  - BACKGROUND: The purpose of this study was to assess the surface characterization
      and frictional resistance between stainless steel brackets and two types of
      orthodontic wires made of stainless steel and nickel-titanium alloys after
      immersion in a chlorhexidine-containing prophylactic agent. METHODS: Stainless
      steel orthodontic brackets with either stainless steel (SS) or heat-activated
      nickel-titanium (Ni-Ti) wires were immersed in a 0.2% chlorhexidine and an
      artificial saliva environment for 1.5 h. The frictional force was measured on a
      universal testing machine with a crosshead speed of 10 mm/min over a 5-mm of
      archwire. The surface morphology of bracket slots and surface roughness of
      archwires after immersion in chlorhexidine were also characterized using a
      scanning electron microscope (SEM) and an atomic force microscope (AFM),
      respectively. RESULTS: There was no significant difference in the frictional
      resistance values between SS and Ni-Ti wires immersed in either chlorhexidine or
      artificial saliva. The frictional resistance values for the SS and Ni-Ti wires
      immersed in 0.2% chlorhexidine solution were not significantly different from
      that in artificial saliva. No significant difference in the average surface
      roughness for both wires before (as-received) and after immersion in either
      chlorhexidine or artificial saliva was observed. CONCLUSIONS: One-and-half-hour
      immersion in 0.2% chlorhexidine mouthrinse did not have significant influence on
      the archwires surface roughness or the frictional resistance between stainless
      steel orthodontic brackets and archwires made of SS and Ni-Ti. Based on these
      results, chlorhexidine-containing mouthrinses may be prescribed as non
      destructive prophylactic agents on materials evaluated in the present study for
      orthodontic patients.

PMID- 24325760
TI  - The role of serpin and cystatin antiproteases in mucosal innate immunity and
      their defense against HIV.
AB  - Antiproteases play diverse roles in nature, from regulating protease activity to
      innate defense against microorganisms. Recently, antiproteases have been shown to
      play important roles in HIV pathogenesis including, inhibiting HIV binding and
      replication and reducing activation and inflammation of susceptible cells. They
      have also been implicated as one of the initial host responders, in plasma, to
      control replication of HIV. More recently, antiproteases expressed at the mucosal
      surface have been linked to reduced susceptibility to HIV infection in HIV
      exposed sero-negative individuals. These factors are expressed in the epithelial
      layer of the female genital tract, thus at the frontline of defense against
      mucosal infection. This review focuses on the specific antimicrobial roles of
      antiproteases, focusing on serpins and cystatins, with an emphasis on their known
      and potential roles in HIV infection. Their potential as therapeutic
      interventions to combat HIV is also discussed.

PMID- 24325762
TI  - Molecule database framework: a framework for creating database applications with
      chemical structure search capability.
AB  - BACKGROUND: Research in organic chemistry generates samples of novel chemicals
      together with their properties and other related data. The involved scientists
      must be able to store this data and search it by chemical structure. There are
      commercial solutions for common needs like chemical registration systems or
      electronic lab notebooks. However for specific requirements of in-house databases
      and processes no such solutions exist. Another issue is that commercial solutions
      have the risk of vendor lock-in and may require an expensive license of a
      proprietary relational database management system. To speed up and simplify the
      development for applications that require chemical structure search capabilities,
      I have developed Molecule Database Framework. The framework abstracts the storing
      and searching of chemical structures into method calls. Therefore software
      developers do not require extensive knowledge about chemistry and the underlying
      database cartridge. This decreases application development time. RESULTS:
      Molecule Database Framework is written in Java and I created it by integrating
      existing free and open-source tools and frameworks. The core functionality
      includes:*Support for multi-component compounds (mixtures)*Import and export of
      SD-files*Optional security (authorization)For chemical structure searching
      Molecule Database Framework leverages the capabilities of the Bingo Cartridge for
      PostgreSQL and provides type-safe searching, caching, transactions and optional
      method level security. Molecule Database Framework supports multi-component
      chemical compounds (mixtures).Furthermore the design of entity classes and the
      reasoning behind it are explained. By means of a simple web application I
      describe how the framework could be used. I then benchmarked this example
      application to create some basic performance expectations for chemical structure
      searches and import and export of SD-files. CONCLUSIONS: By using a simple web
      application it was shown that Molecule Database Framework successfully abstracts
      chemical structure searches and SD-File import and export to simple method calls.
      The framework offers good search performance on a standard laptop without any
      database tuning. This is also due to the fact that chemical structure searches
      are paged and cached. Molecule Database Framework is available for download on
      the projects web page on bitbucket:
      https://bitbucket.org/kienerj/moleculedatabaseframework.

PMID- 24325761
TI  - The effects of ABCC2 G1249A polymorphism on the risk of resistance to
      antiepileptic drugs: a meta-analysis of the literature.
AB  - AIMS: The G1249A variant of the multidrug resistance-associated protein 2 (ABCC2)
      gene may be associated with the development of antiepileptic drug (AED)
      resistance. Although numerous studies have investigated the association between
      the G1249A variant and the risk of drug resistance in epilepsy, the results of
      these studies have been inconclusive. To assess the role of G1249A polymorphism
      in drug resistance in epilepsy, a meta-analysis was performed. MATERIALS AND
      METHODS: We systematically reviewed relevant studies retrieved by the PubMed and
      Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
      based on the date extracted from the studies to evaluate the strength of
      association. We also analyzed the heterogeneity and sensitivity of each report
      and the publication bias of the studies. RESULTS: A total of 6 published studies,
      involving 2213 patients (1100 patients with drug-resistant epilepsy and 1113
      controls with drug-responsive epilepsy) were reviewed in the present meta
      analysis. The overall results indicated that the variant genotypes were
      associated with a significantly decreased risk of AED resistance (AA vs. GG:
      OR=0.372, 95% CI=0.182-0.762; recessive model: OR=0.399, 95% CI=0.200-0.795)
      (fixed-effects model). A stratified analysis by ethnicity showed similar findings
      for Caucasians in an additive model (A vs. G: OR=0.700, 95% CI=0.494-0.992).
      CONCLUSIONS: The meta-analysis suggests that the ABCC2 G1249A polymorphism is
      significantly associated with a decreased risk of AED resistance. However,
      further functional investigations are warranted to validate the association.

PMID- 24325763
TI  - Applying the workload indicators of staffing need (WISN) method in Namibia:
      challenges and implications for human resources for health policy.
AB  - INTRODUCTION: As part of ongoing efforts to restructure the health sector and
      improve health care quality, the Ministry of Health and Social Services (MoHSS)
      in Namibia sought to update staffing norms for health facilities. To establish an
      evidence base for the new norms, the MoHSS supported the first-ever national
      application of the Workload Indicators of Staffing Need (WISN) method, a human
      resource management tool developed by the World Health Organization. APPLICATION:
      The WISN method calculates the number of health workers per cadre, based on
      health facility workload. It provides two indicators to assess staffing: (1) the
      gap/excess between current and required number of staff, and (2) the WISN ratio,
      a measure of workload pressure. Namibian WISN calculations focused on four cadres
      (doctors, nurses, pharmacists, pharmacy assistants) and all four levels of public
      facilities (clinics, health centers, district hospitals, intermediate hospitals).
      WISN steps included establishing a task force; conducting a regional pilot;
      holding a national validation workshop; field verifying data; collecting,
      uploading, processing, and analyzing data; and providing feedback to policy
      makers. CHALLENGES: The task force faced two challenges requiring time and effort
      to solve: WISN software-related challenges and unavailability of some data at the
      national level. FINDINGS: WISN findings highlighted health worker shortages and
      inequities in their distribution. Overall, staff shortages are most profound for
      doctors and pharmacists. Although the country has an appropriate number of
      nurses, the nurse workforce is skewed towards hospitals, which are adequately or
      slightly overstaffed relative to nurses' workloads. Health centers and, in
      particular, clinics both have gaps between current and required number of nurses.
      Inequities in nursing staff also exist between and within regions. Finally, the
      requirement for nurses varies greatly between less and more busy clinics (range =
      1 to 7) and health centers (range = 2 to 57). POLICY IMPLICATIONS: The utility of
      the WISN health workforce findings has prompted the MoHSS to seek approval for
      use of WISN in human resources for health policy decisions and practices. The
      MoHSS will focus on revising staffing norms; improving staffing equity across
      regions and facility types; ensuring an appropriate skill mix at each level; and
      estimating workforce requirements for new cadres.

PMID- 24325764
TI  - Human papillomavirus genotypes in human immunodeficiency virus-positive patients
      with anal pathology in Madrid, Spain.
AB  - BACKGROUND: We studied anal specimens to determine the distribution of human
      papillomavirus (HPV) genotypes and co-infection occurrence. This information will
      contribute to the knowledge of HPV genotype distributions and provide an estimate
      of the prevalence of different oncogenic HPV genotypes found in patients in
      Madrid (Spain). METHODS: We studied a total of 82 anal biopsies from the Hospital
      General Universitario Gregorio Maranon of Madrid. These included 4 specimens with
      benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion,
      24 specimens with high-grade anal squamous intraepithelial lesions and 2
      specimens with invasive anal carcinoma. HPV genotyping was performed with PCR
      amplification and reverse dot blot hybridization. RESULTS: We detected 33
      different HPV genotypes, including 16 HPVs associated with a high risk of
      carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and
      14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an
      uncharacterized HPV genotype was detected. The most frequent HPV genotypes found
      were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV
      43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%
      3.2%) of the total viruses detected in all lesions. HPV co-infections were found
      in 83.9% of all types of lesions. The majority of cases (90.2%) were
      concomitantly infected with the human immunodeficiency virus (HIV). CONCLUSION:
      The prevalence of high-risk carcinogenic genotypes in anal pathological samples
      was remarkable. Therefore, further studies that include a greater number of
      samples, particularly invasive carcinoma cases are needed to evaluate the
      potential influence of these HPV genotypes in the appearance of anal carcinomas.
      Also, the influence of other accompanying infections should be evaluated clarify
      the appearance of this type of carcinoma. VIRTUAL SLIDES: The virtual slide(s)
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2075238024106058.

PMID- 24325765
TI  - A comparison of Chinese and non-Chinese Canadian patients hospitalized with heart
      failure.
AB  - BACKGROUND: Canadians of Chinese descent, represent one of the fastest growing
      visible minority groups in Canada, (as well as the second largest), but
      relatively little is known about the clinical features of heart failure (HF) in
      Chinese-Canadian versus non-Chinese Canadian patients. METHODS: We conducted a
      population-based analysis of urban patients hospitalized in Ontario, Canada for
      the first time with a most responsible diagnosis of HF between April 1, 1995 and
      March 31, 2008. Among the 99,278 patients, 1,339 (1.3%) were classified as
      Chinese using a previously validated list of Chinese surnames. Through linkage to
      other administrative databases, we compared the clinical characteristics,
      pharmacological management, and outcomes of Chinese versus non-Chinese HF
      patients. RESULTS: Ischemic heart disease was identified as the possible etiology
      of HF in a greater proportion of non-Chinese patients (47.7% vs. 35.3%; p <
      0.001) whereas hypertension (26.1% vs. 16.1%; p < 0.001) and valvular heart
      disease (11.6% vs. 7.2%; p < 0.001) were relatively more common in Chinese
      patients. Chinese patients were prescribed angiotensin-converting enzyme (ACE)
      inhibitors less frequently (57.5% vs. 66.4%, p < 0.001) and angiotensin receptor
      blockers (ARBs) more frequently (17.4% vs. 8.9%, p < 0.001) compared to non
      Chinese patients. They were also less likely to be adherent to ACE inhibitors
      over a 1-year follow up period. However, the 1-year case-fatality rates were
      comparable between the Chinese (31.7%) and non-Chinese (30.2%) subjects (p =
      0.24). CONCLUSION: There are important differences in the causes and medical
      management of HF in Chinese and non-Chinese patients residing in Canada. Despite
      these differences, the long-term outcomes of HF patients were similar.

PMID- 24325766
TI  - Children under the age of seven with diabetes are increasing their cardiovascular
      risk by their food choices.
AB  - AIM: Early-onset diabetes increases the risk of cardiovascular disease. This
      study examined the eating habits of children under 7 years of age with diabetes
      to see whether their diet increased that risk even further. METHODS: A total of
      24 children with type 1 diabetes (mean age 4.5 years) and 27 healthy controls
      (mean age 4.6 years) participated in this cross-sectional study. Food intake was
      assessed by two 4-day food records. RESULTS: Children with type 1 diabetes had a
      higher energy intake from protein (18 vs 15%, p < 0.05) and fat (35 vs 31%, p <
      0.05) but lower intake from carbohydrates (47 vs 54%, p < 0.05), than the healthy
      control group. Intake of saturated fat was higher than recommended in both
      groups, and consumption of fruit and vegetables was lower than recommended, but
      similar, in both the diabetes and control groups (191 vs 207 g per day). Total
      intake of fat was negatively correlated with intake of fruit and vegetables (r = 
      0.74 p < 0.05) in children with type 1 diabetes. CONCLUSION: Children under 7
      years of age with type 1 diabetes eat too much saturated fat and not enough fruit
      and vegetables. Their diet should be improved to reduce their cardiovascular
      risk.

PMID- 24325767
TI  - Bullying victimization among college students: negative consequences for alcohol
      use.
AB  - This study reports the prevalence of bullying victimization at school and work
      among college freshmen and the relationships between victimization and changes in
      alcohol consumption and alcohol problems. Web survey data at 2 time points from a
      sample of 2118 freshmen from 8 colleges and universities in the Midwestern United
      States indicated that 43% of students experienced bullying at school and that 33%
      of students experienced bullying at work. Bullying, particularly at school,
      consistently predicted alcohol consumption and problematic drinking, after
      controlling for baseline drinking and other school and work stressors. 

PMID- 24325768
TI  - Psychopathological stability of personality disorders in substance abuse patients
      treated in a therapeutic community.
AB  - The objective of this study is to explore the stability of personality dimensions
      in a selection of psychoactive substance abuse patients during treatment in
      therapeutic communities. The baseline assessment was conducted 15 to 20 days from
      the start of therapeutic community treatment, and the second assessment was
      conducted 3 months after admission. The Millon Clinical Multiaxial Inventory III
      was used to assess personality dimensions. At 3 months, a reduction was observed
      in the mean severity scores of most personality dimensions in both patterns and
      clinical syndromes. Caution should be exercised when assessing and diagnosing
      personality disorders in a drug addict population because one must consider the
      presence of abuse concomitant factors that may erroneously increase the
      comorbidity of personality disorders and related substance abuse disorders.

PMID- 24325769
TI  - Gender differences in alcohol and drug use among Hispanic adults: the influence
      of family processes and acculturation.
AB  - We examine the influence of family processes and acculturation for gender
      differences in alcohol and drug use among a sample representative of the Hispanic
      population in Miami-Dade County, Florida (N = 734). We found that (a) increases
      in age at marriage and acculturation were associated with greater substance use,
      (b) the associations between age at marriage, acculturation, and substance use
      were found to be greater for Hispanic women than men, and (c) with each
      additional child born, Hispanic women are increasingly less likely to use
      substances than Hispanic men. Data reveal that family processes and acculturation
      jointly impact substance use.

PMID- 24325770
TI  - Correlates of risky alcohol and methamphetamine use among currently homeless male
      parolees.
AB  - Homeless men on parole are a hard-to-reach population with significant community
      reintegration challenges. This cross-sectional study describes sociodemographic,
      cognitive, psychosocial, and drug-related correlates of alcohol and
      methamphetamine use in 157 homeless male parolees (age range 18-60) enrolled in a
      substance abuse treatment center in Los Angeles, California. Logistic regression
      results revealed that being African American and older were negatively related to
      methamphetamine use, whereas being older and more hostile were related to riskier
      alcohol abuse. Findings from this study provide a greater understanding of
      correlates of methamphetamine and alcohol--two of the most detrimental forms of
      substances abused among currently homeless parolees. 

PMID- 24325771
TI  - The effects of a tobacco intervention on binge drinking among African American
      light smokers.
AB  - Tobacco use and binge drinking are commonly associated with each other and
      research has shown that reducing smoking may influence alcohol use in alcohol
      dependent populations. Although African Americans report a lower prevalence of
      binge drinking than other racial/ethnic groups, they are more likely to report
      consequences associated with this behavior. The aim of this article was to study
      the effect of a smoking intervention (counseling) on binge drinking prevalence
      and the frequency and average daily alcohol consumption in a sample of African
      American light smokers (those who smoke 10 cigarettes or less per day).
      Multivariate models were used to assess whether counseling type (health education
      or motivational interviewing) affected binge drinking prevalence and frequency or
      average daily alcohol consumption among participants (N = 755). Generalized
      linear models were run to assess the mediation effect of smoking cessation on the
      relationship between the counseling intervention and drinking outcomes. Finally,
      smoking cessation (regardless of counseling type) was assessed to determine the
      effect on alcohol use outcomes. Overall, counseling type was significantly
      related to a reduction in past 30-day binge drinking prevalence at week 8 among
      participants in the health education counseling (P = .045); however, these
      results diminished within 6 months. Smoking cessation did not appear to mediate
      the relationship between counseling type and alcohol use outcomes. Regardless of
      counseling type, individuals who quit smoking within the first 8 weeks of the
      study reported lower past 30-day binge drinking prevalence at week 8 than those
      who did not quit during the first 8 weeks (P = .035), but the effect was not
      sustained at the end of the study (week 26). These results show that tobacco
      interventions can affect binge drinking, but the effect does not appear to be
      sustained over time. 

PMID- 24325772
TI  - An ECG-based cardiac safety initiative is well received by opioid treatment
      program staff: results from a qualitative assessment.
AB  - Registry data on methadone reveal that QTc-prolongation is reported more often
      among opioid-dependent patients than chronic pain patients. This suggests that
      opioid treatment programs may be an important venue for implementing arrhythmia
      risk-reduction strategies. An electrocardiography-based strategy in the opioid
      treatment program setting demonstrated a reduction in the QTc-interval among
      patients with marked QTc-prolongation. However, the feasibility of program
      implementation remains uncertain. Therefore, we performed qualitative interviews
      among opioid treatment program staff to determine the barriers and benefits of
      implementation. Overall, the program was well received by staff; however, a need
      for training and algorithms was identified. No patient was denied access to care.

PMID- 24325773
TI  - Venlafaxine abuse in a patient with schizophrenia and prior history of substance
      dependence: a case report.
AB  - Venlafaxine is a serotonin/norepinephrine reuptake inhibitor that is believed to
      have no abuse potential. Currently, 2 published case reports argue against this
      notion. This article describes a third case of venlafaxine abuse and the first in
      the literature on a patient with schizophrenia. This article will also review the
      literature on venlafaxine abuse and propose a pharmacological explanation for its
      abuse potential. Healthcare practitioners need to be cautious when prescribing
      venlafaxine and other neuromodulatory medications. 

PMID- 24325774
TI  - Kratom exposures reported to Texas poison centers.
AB  - Kratom use is a growing problem in the United States. Kratom exposures reported
      to Texas poison centers between January 1998 and September 2013 were identified.
      No kratom exposures were reported from 1998 to 2008 and 14 exposures were
      reported from 2009 to September 2013. Eleven patients were male, and 11 patients
      were in their 20s. The kratom was ingested in 12 patients, inhaled in 1, and both
      ingested and inhaled in 1. Twelve patients were managed at a healthcare facility
      and the remaining 2 were managed at home. 

PMID- 24325775
TI  - Educating providers for the epidemic: the role of AOAAM.

PMID- 24325777
TI  - Development of a multiplex PCR for the identification of major pathogenic
      bacteria of post-partum endometritis in dairy cows.
AB  - Post-partum period has an important role in cows' breeding due to its effects on
      reproductive efficiency and subsequent pregnancy. Escherichia coli, Trueperella
      pyogenes (Arcanobacterium pyogenes), Fusobacterium necrophorum and Prevotella
      melaninogenicus are recognized as major pathogens associated with uterine
      endometrial lesions. The objective of this study was to identify these pathogens
      using the polymerase chain reaction (PCR) as a culture-independent sensitive
      method. A total of 172 cows were examined 25-35 days post-partum, and 128 cows
      were examined at 2 weeks later (39-49 days post-partum). Uterine discharges were
      collected by covered plastic infusion pipettes. The prevalence of endometritis
      was greater in the first examination than the second (35.5% vs. 16%). E. coli was
      detected in eight of the samples, T. pyogenes was detected in 13 of the samples
      and F. necrophorum was detected in 11 of the samples. There was no positive
      sample of P. melaninogenicus. Uterine contamination by T. pyogenes and F.
      necrophorum in the first examination was higher than the second examination. T.
      pyogenes affected as a tendency the prevalence of clinical endometritis in first
      examination. Primiparous cows showed 4.02 times higher odds of clinical
      endometritis compared with second-parity cows in first examination. A multiplex
      PCR protocol as a simple, less expensive, fast assay was introduced to identify
      E. coli, T. pyogenes and F. necrophorum.

PMID- 24325778
TI  - Simvastatin and bezafibrate increase cholesterol efflux in men with type 2
      diabetes.
AB  - BACKGROUND: The importance of functional properties of high-density lipoproteins
      (HDL) for atheroprotection is increasingly recognized. We determined the impact
      of lipid-lowering therapy on 3 key HDL functionalities in Type 2 diabetes
      mellitus (T2DM). MATERIALS AND METHODS: A placebo-controlled, randomized cross
      over study (three 8-week treatment periods with simvastatin (40 mg daily),
      bezafibrate (400 mg daily), alone and in combination) was carried out in 14 men
      with T2DM. Cholesterol efflux was determined using human THP-1 monocyte-derived
      macrophages, HDL antioxidative capacity was measured as inhibition of low-density
      lipoprotein oxidation in vitro, and HDL anti-inflammatory capacity was assessed
      as suppression of thrombin-induced monocyte chemotactic protein 1 expression in
      human umbilical vein endothelial cells. Pre-beta-HDL was assayed using crossed
      immunoelectrophoresis. RESULTS: While cholesterol efflux increased in response to
      simvastatin, bezafibrate and combination treatment (+12 to +23%; anova, P =
      0.001), HDL antioxidative capacity (P = 0.23) and HDL anti-inflammatory capacity
      (P = 0.15) did not change significantly. Averaged changes in cellular cholesterol
      efflux during active treatment were correlated positively with changes in HDL
      cholesterol, apoA-I and pre-beta-HDL (P < 0.05 to P < 0.001). There were no inter
      relationships between changes in the three HDL functionalities during treatment
      (P > 0.10). Changes in HDL antioxidative capacity and anti-inflammatory capacity
      were also unrelated to changes in HDL cholesterol and apoA-I, while changes in
      HDL antioxidative capacity were related inversely to pre-beta-HDL (P < 0.05).
      CONCLUSION: Simvastatin and bezafibrate increase cholesterol efflux, parallel to
      HDL cholesterol and apoA-I responses. The antioxidative and anti-inflammatory
      properties of HDL are not to an important extent affected by these therapeutic
      interventions.

PMID- 24325779
TI  - Gestational length demonstrates natural variation.

PMID- 24325780
TI  - The significance of eosinophils in hypertrophic lichen planus.
AB  - BACKGROUND: Hypertrophic lichen planus (LP) is a variant of LP favoring the lower
      extremities and showing prominent epidermal hyperplasia and hyperorthokeratosis.
      Contrary to dogma that eosinophils are rare in LP and variants, we noticed that
      some cases of hypertrophic LP have eosinophils in the absence of drug history.
      METHODS: Retrospective review of all cases of hypertrophic LP over 22 consecutive
      years was conducted. The number of eosinophils in 10 representative * 20-fields
      was counted in the area of densest dermal infiltrate. Cases of classic LP were
      used for comparison. Clinical parameters on all cases were recorded. RESULTS: The
      two groups were clinically similar. The average number of eosinophils per 10 * 20
      fields in 63 cases of hypertrophic LP was 10.5 with a range between 0 and 200.
      Thirteen of 63 cases (20.6%) had more than 10 eosinophils per 10 * 20-fields. The
      average number of eosinophils in 17 cases of classic LP was 1.6 (p = 0.016) with
      a range between 0 and 9 and no cases with more than 10 eosinophils (p = 0.06).
      CONCLUSION: Hypertrophic LP is a distinct variant of LP that may show variable
      numbers of eosinophils and should be included in the differential diagnosis of
      lichenoid dermatitis with eosinophils.

PMID- 24325781
TI  - Effects of dietary supplementation of glucosamine sulfate on intestinal
      inflammation in a mouse model of experimental colitis.
AB  - BACKGROUND AND AIM: Epidemiological evidences suggested an inverse association
      between the use of glucosamine supplements and colorectal cancer (CRC) risk. In
      this study, the efficacy of glucosamine to attenuate dextran sodium sulfate (DSS)
      induced colitis, a precancerous condition for CRC, was evaluated. METHODS:
      C57BL/6 mice were separated into three groups receiving glucosamine sulfate at
      concentrations of 0, 0.05, and 0.10% (w/w) of AIN-93G diet, respectively for 4
      weeks. Colitis was induced by supplying two cycles (5 days per cycle) of 2% DSS
      in the animals' drinking water. RESULTS: Glucosamine supplementation at the level
      of 0.10% of the diet (w/w) reduced colitis-associated symptoms as measured by
      disease activity index (DAI). Tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta, and nuclear factor-kappa B mRNA expression in the colonic
      mucosa was significantly lower in animals fed 0.10% glucosamine compared with
      those of the control group. Expression of the tight junction proteins ZO-1 and
      occludin was significantly higher in the 0.10% glucosamine-supplemented group
      compared with the other groups. Also, colonic protein expression of lipocalin 2,
      and serum concentrations of interleukin-8 and amyloid P component (SAP) were
      significantly reduced in the 0.10% glucosamine-supplemented group compared with
      the control group. CONCLUSION: These results suggest that glucosamine attenuates
      the colitis disease activity by suppressing NF-kappaB activation and related
      inflammatory responses.

PMID- 24325782
TI  - Aminocyanation by the addition of N-CN bonds to arynes: chemoselective synthesis
      of 1,2-bifunctional aminobenzonitriles.
AB  - An efficient aminocyanation by the direct addition of aryl cyanamides to arynes
      is described, enabling incorporation of highly useful amino and cyano groups
      synchronously via cleavage of inert N-CN bonds, affording synthetically useful
      1,2-bifunctional aminobenzonitriles. The postsynthetic functionalization of the
      aminocyanation products allows diverse formation of synthetically important
      derivatives such as drug molecule Ponstan and fused heterocycles. 

PMID- 24325783
TI  - Three-dimensional methodology for photogrammetric acquisition of the soft tissues
      of the face: a new clinical-instrumental protocol.
AB  - BACKGROUND: The objective of this study is to define an acquisition protocol that
      is clear, precise, repeatable, simple, fast and that is useful for analysis of
      the anthropometric characteristics of the soft tissue of the face. METHODS: The
      analysis was carried out according to a new clinical-instrumental protocol that
      comprises four distinct phases: (1) setup of portable equipment in the space in
      which field analysis will be performed, (2) preparation of the subject and
      spatial positioning, (3) scanning of the subject with different facial
      expressions, and (4) treatment and processing of data. The protocol was tested on
      a sample comprising 66 female subjects (64 Caucasian, 1 Ethiopian, and 1
      Brazilian) who were the finalists of an Italian national beauty contest in 2010.
      To illustrate the potential of the method, we report here the measurements and
      full analysis that were carried out on the facial model of one of the subjects
      who was scanned. RESULTS: This new protocol for the acquisition of faces is shown
      to be fast (phase 1, about 1 h; phase 2, about 1.5 min; phase 3, about 1.5 min;
      phase 4, about 15 min), simple (phases 1 to 3 requiring a short operator training
      period; only phase 4 requires expert operators), repeatable (with direct
      palpation of anatomical landmarks and marking of their positions on the face, the
      problem of identification of these same landmarks on the digital model is
      solved), reliable and precise (average precision of measurements, 0.5 to 0.6 mm
      over the entire surface of the face). CONCLUSIONS: This standardization allows
      the mapping of the subjects to be carried out following the same conditions in a
      reliable and fast process for all of the subjects scanned.

PMID- 24325784
TI  - Automatic classification of atypical lymphoid B cells using digital blood image
      processing.
AB  - INTRODUCTION: There are automated systems for digital peripheral blood (PB) cell
      analysis, but they operate most effectively in nonpathological blood samples. The
      objective of this work was to design a methodology to improve the automatic
      classification of abnormal lymphoid cells. METHODS: We analyzed 340 digital
      images of individual lymphoid cells from PB films obtained in the CellaVision
      DM96:150 chronic lymphocytic leukemia (CLL) cells, 100 hairy cell leukemia (HCL)
      cells, and 90 normal lymphocytes (N). We implemented the Watershed Transformation
      to segment the nucleus, the cytoplasm, and the peripheral cell region. We
      extracted 44 features and then the clustering Fuzzy C-Means (FCM) was applied in
      two steps for the lymphocyte classification. RESULTS: The images were
      automatically clustered in three groups, one of them with 98% of the HCL cells.
      The set of the remaining cells was clustered again using FCM and texture
      features. The two new groups contained 83.3% of the N cells and 71.3% of the CLL
      cells, respectively. CONCLUSION: The approach has been able to automatically
      classify with high precision three types of lymphoid cells. The addition of more
      descriptors and other classification techniques will allow extending the
      classification to other classes of atypical lymphoid cells.

PMID- 24325785
TI  - MiR-92b inhibitor promoted glioma cell apoptosis via targeting DKK3 and blocking
      the Wnt/beta-catenin signaling pathway.
AB  - BACKGROUND: MiR-92b was upregulated in gliomas. However, the association of miR
      92b with glioma cell apoptosis and survival remains unknown. METHODS:
      Proliferation capability of glioma cells upon tranfection with miR-92b mimics or
      inhibitors was detected by mutiple analyses, including MTT assays, colony
      formation assay. Apoptosis abilities of glioma cells were detected by flow
      cytometric analysis. The target of miR-92b was determined by luciferase reporter
      and western blot. The association of miR-92b with outcome was examined in twenty
      glioma patients. RESULTS: MiR-92b expression was significantly increased in high
      grade gliomas compared with low-grade gliomas, and positively correlated with the
      degree of glioma infiltration. Over-expression of miR-92b increased cell
      proliferation, whereas knockdown of miR-92b decreased cell proliferation via
      modulating the levels of the target, Target prediction analysis and a dual
      luciferase reporting assay confirmed that the inhibitory protein-coding Dickkopf
      3 gene (DKK3) was a direct target of miR-92b. Furthermore, miR-92b could regulate
      the expression of downstream genes of the Wnt/beta-catenin signaling pathway,
      such as Bcl2, c-myc and p-c-Jun, in glioma cells. Finally, the increased level of
      miR-92b expression in high-grade gliomas confers poorer overall survival.
      CONCLUSIONS: The present data indicates that miR-92b directly regulate cell
      proliferation and apoptosis by targeting DKK3 and act as prognostic factors for
      glioma patients.

PMID- 24325786
TI  - Comparative oral bioavailability of geniposide following oral administration of
      geniposide, Gardenia jasminoides Ellis fruits extracts and Gardenia herbal
      formulation in rats.
AB  - OBJECTIVE: The aim of this study was to compare the oral bioavailability and
      pharmacokinetic data between pure compound of the major active component, single
      herbal extract and complex herbal formulation by determining bioavailability of
      geniposide in each group following intravenous and oral administrations. METHODS:
      A conscious and freely moving rat model was used in this experiment to avoid the
      stress caused by restraint or anaesthesia. The pure compound of geniposide,
      Gardenia fruits (Chinese name: Zhi-Zi), and extracts of a Gardenia herbal
      formulation (Chinese name: Zhi-Zi-Chi-Tang) were administered at doses of 200
      mg/kg, 4.69 g/kg and 10.82 g/kg for oral administration and fed by gavages to
      rats, respectively. The earlier doses are equivalent to geniposide administration
      dose of 200 mg/kg. KEY FINDINGS: The results show that after oral administration
      of geniposide, Gardenia fruits and Gardenia herbal formulation, the
      bioavailability were 4.23%, 32.32% and 27.17%, respectively. The results of oral
      bioavailability of geniposide also suggest that Gardenia fruits extract, single
      herb, is a more efficient way for geniposide, pure compound, absorption than
      traditional herbal formulation administration and direct pure compound
      administration. CONCLUSIONS: The conclusion reveals that herbal ingredient
      ingredient or herb-herb interaction may affect the oral absorption of geniposide
      related herbal formulation.

PMID- 24325787
TI  - State of the science on controversial topics: orthodontic therapy and gingival
      recession (a report of the Angle Society of Europe 2013 meeting).
AB  - BACKGROUND: Controversy exists in the literature between the role of orthodontic
      treatment and gingival recession. Whilst movement of teeth outside the alveolar
      bone has been reported as a risk factor for gingival recession, others have found
      no such association. FINDINGS: The Angle Society of Europe devoted a study day to
      explore the evidence surrounding these controversies. The aim of the day was for
      a panel of experts to evaluate the current evidence base in relation to either
      the beneficial or detrimental effects of orthodontic treatment on the gingival
      tissue. CONCLUSIONS: There remains a relatively weak evidence base for the role
      of orthodontic treatment and gingival recession and thus a need to undertake a
      risk assessment and appropriate consent prior to the commencement of treatment.
      In further prospective, well designed trials are needed.

PMID- 24325788
TI  - Long-term survival of patients with hepatocellular carcinoma with inferior vena
      cava tumor thrombus treated with sorafenib combined with transarterial
      chemoembolization: report of two cases and literature review.
AB  - The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus formation in
      the main vasculature is extremely poor. Sorafenib combined with transarterial
      chemoembolization is a novel treatment approach for advanced HCC. In this study,
      we report two HCC patients with inferior vena cava tumor thrombus who underwent
      the combination treatment. The overall survival times for these two patients were
      44 months and 35 months, respectively. Our report suggests that sorafenib
      combined with transarterial chemoembolization may be a viable choice for patients
      with advanced HCC even with inferior vena cava tumor thrombus. Further studies
      are required to verify the efficacy and safety of this combination therapy for
      patients with advanced HCC with inferior vena cava tumor thrombus. 

PMID- 24325790
TI  - Radiation and concomitant chemotherapy for patients with glioblastoma multiforme.
AB  - Postoperative external beam radiotherapy was considered the standard adjuvant
      treatment for patients with glioblastoma multiforme until the advent of using the
      drug temozolomide (TMZ) in addition to radiotherapy. High-dose volume should be
      focal, minimizing whole brain irradiation. Modern imaging, using several magnetic
      resonance sequences, has improved the planning target volume definition. The
      total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0
      Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the
      standard of care for glioblastoma multiforme patients. Radiotherapy dose
      intensification and radiosensitizer approaches have not improved the outcome. In
      spite of the lack of high quality evidence, stereotactic radiotherapy can be
      considered for a selected group of patients. For elderly patients, data suggest
      that the same survival benefit can be achieved with similar morbidity using a
      shorter course of radiotherapy (hypofractionation). Elderly patients with tumors
      that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter
      can benefit from TMZ alone. 

PMID- 24325789
TI  - Molecular biology of high-grade gliomas: what should the clinician know?
AB  - The current World Health Organization classification system of primary brain
      tumors is solely based on morphologic criteria. However, there is accumulating
      evidence that tumors with similar histology have distinct molecular signatures
      that significantly impact treatment response and survival. Recent practice
      changing clinical trials have defined a role for routine assessment of O-6
      methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma
      patients, especially in the elderly, and 1p and 19q codeletions in patients with
      anaplastic glial tumors. Recently discovered molecular alterations including
      mutations in IDH-1/2, epidermal growth factor receptor (EGFR), and BRAF also have
      the potential to become targets for future drug development. This article aims to
      summarize current knowledge on the molecular biology of high-grade gliomas
      relevant to daily practice. 

PMID- 24325791
TI  - Progesterone induced blocking factor isoforms in normal and failed murine
      pregnancies.
AB  - PROBLEM: Progesterone induced blocking factor (PIBF) is required for successful
      pregnancy. Alternative splicing produces PIBF isoforms with different functions.
      The full-length (90 kDa) PIBF is involved in cell cycle regulation, whereas
      smaller secreted forms act as cytokines. We aim to examine the PIBF exon pattern
      and protein isoform profile in normal and failed murine pregnancies. METHOD OF
      STUDY: Pregnant Balb/c mice were killed on gestation days 12-14 or 17-19. Normal
      and resorbed fetuses, placentae, and uterine tissue were used for RNA and protein
      analysis with RT-PCR and Western blot, respectively. RESULTS: Late pregnancy and
      resorption were associated with lower expression of the N-terminal exons,
      together with significantly reduced production of the full-length protein.
      CONCLUSION: Reduced production of the full-length PIBF protein might result in
      disturbed cell cycle regulation and dysregulated trophoblast invasion, while the
      absence of PIBF isoforms containing exon 2-4 coded sequences might lead to the
      loss of local immunosuppression.

PMID- 24325792
TI  - The distinct expression patterns of claudin-10, -14, -17 and E-cadherin between
      adjacent non-neoplastic tissues and gastric cancer tissues.
AB  - BACKGROUND: Recent data indicate that the cell adhesion proteins are abnormally
      regulated in several human cancers and the expression of the cell adhesion
      proteins E-cadherin and claudin proteins is involved in the etiology and
      progression of cancer. It is clear that these protein represent promising targets
      for cancer detection, diagnosis, and therapy. METHODS: To explore the expression
      distinction of the cell adhesion proteins claudin-10,-14,-17 and E-cadherin in
      the adjacent non-neoplastic tissues and gastric cancer tissues, 50 gastric cancer
      tissues and 50 samples of adjacent non-neoplastic tissues adjacent to the tumors
      were examined for expression of claudin-10,-14,-17 and E-cadherin by streptavidin
      perosidase immunohistochemical staining method. RESULTS: The positive expression
      rates of E-cadherin in gastric cancer tissues and adjacent non-neoplastic tissues
      were 32% and 74% respectively (P < 0.01). The positive expression rates of
      claudin-10 in gastric cancer tissues and adjacent non-neoplastic tissues were 24%
      and 72% respectively (P < 0.01). The positive expression rates of claudin-17 in
      gastric cancer tissues and adjacent non-neoplastic tissues were 18% and 70% (P <
      0.01). In contrast, the positive expression rates of claudin-14 in gastric cancer
      tissues and adjacent non-neoplastic tissues were 58% and 24% respectively (P =
      0.015 < 0.05) Thus in our study, the expression of E-cadherin, claudin-10, and
      claudin-17 was down-regulated in gastric cancer tissue while the expression of
      claudin-14 was up-regulated. Correlations between claudins and E-cadherin
      expression with lymphatic metastasis were observed. CONCLUSION: Our study reveals
      that the expression of E-cadherin, claudin-10, and claudin-17 were down-regulated
      in gastric cancer tissue while the expression of claudin-14 was up-regulated and
      correlation between claudins and E-cadherin expression with lymphatic metastasis
      were observed. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/1475928069111326.

PMID- 24325793
TI  - Rhinocerebral zygomycosis with pansinusitis in a 14-year-old girl with type 1
      diabetes: a case report and review of the literature.
AB  - BACKGROUND: Zygomycosis is a rare life-threatening fungal infection affecting
      mostly patients with predisposing conditions such as diabetes mellitus,
      immunodeficiency, haemochromatosis or major trauma. METHODS: We describe a case
      of rhinocerebral zygomycosis in a girl with type 1 diabetes and review previous
      published cases and treatment options. RESULTS: A 14-year-old girl with type 1
      diabetes mellitus occurred with dental pain, facial swelling, ecchymosis and left
      eye decreased visual acuity, unresponsive to antibiotic therapy. The cultures of
      the sinusal mucosa were positive for fungal species belonging to the Zygomycetes.
      She performed antifungal therapy with posaconazole (POS) with a very slow
      improvement and a poor glycemic control, leading to blindness of the left eye.
      CONCLUSION: Our report adds further awareness on rhinocerebral zygomycosis and
      emphasizes on urgent diagnosis and timely management of this potentially fatal
      fungal infection through an adequate treatment.

PMID- 24325794
TI  - Poor glycemic control in younger women attending Malaysian public primary care
      clinics: findings from adults diabetes control and management registry.
AB  - BACKGROUND: Women of reproductive age are a group of particular concern as
      diabetes may affect their pregnancy outcome as well as long-term morbidity and
      mortality. This study aimed to compare the clinical profiles and glycemic control
      of reproductive and non-reproductive age women with type 2 diabetes (T2D) in
      primary care settings, and to determine the associated factors of poor glycemic
      control in the reproductive age group women. METHODS: This was a cross-sectional
      study using cases reported by public primary care clinics to the Adult Diabetes
      Control and Management registry from 1st January to 31st December 2009. All
      Malaysian women aged 18 years old and above and diagnosed with T2D for at least 1
      year were included in the analysis. The target for glycemic control (HbA1c <
      6.5%) is in accordance to the recommended national guidelines. Both univariate
      and multivariate approaches of logistic regression were applied to determine
      whether reproductive age women have an association with poor glycemic control.
      RESULTS: Data from a total of 30,427 women were analyzed and 21.8% (6,622) were
      of reproductive age. There were 12.5% of reproductive age women and 18.0% of non
      reproductive age women that achieved glycemic control. Reproductive age group
      women were associated with poorer glycemic control (OR = 1.5, 95% CI = 1.2-1.8).
      The risk factors associated with poor glycemic control in the reproductive age
      women were being of Malay and Indian race, longer duration of diabetes, patients
      on anti-diabetic agents, and those who had not achieved the target total
      cholesterol and triglycerides. CONCLUSION: Women with T2D have poor glycemic
      control, but being of reproductive age was associated with even poorer control.
      Health care providers need to pay more attention to this group of patients
      especially for those with risk factors. More aggressive therapeutic strategies to
      improve their cardiometabolic control and pregnancy outcome are warranted.

PMID- 24325795
TI  - Evaluation of shear bond strength of orthodontic brackets using trans
      illumination technique with different curing profiles of LED light-curing unit in
      posterior teeth.
AB  - BACKGROUND: Although using light-cured composites for bonding orthodontic
      brackets has become increasingly popular, curing light cannot penetrate the
      metallic bulk of brackets and polymerization of composites is limited to the
      edges. Limited access and poor direct sight may be a problem in the posterior
      teeth. Meanwhile, effectiveness of the trans-illumination technique is
      questionable due to increased bucco-lingual thickness of the posterior teeth.
      Light-emitting diode (LED) light-curing units cause less temperature rise and
      lower risk to the pulpal tissue. The purpose of this study was to evaluate the
      clinical effectiveness of trans-illumination technique in bonding metallic
      brackets to premolars, using different light intensities and curing times of an
      LED light-curing unit. METHODS: Sixty premolars were randomly divided into six
      groups. Bonding of brackets was done with 40- and 80-s light curing from the
      buccal or lingual aspect with different intensities. Shear bond strengths of
      brackets were measured using a universal testing machine. Data were analyzed by
      one-way analysis of variance test and Duncan's post hoc test. RESULTS: The
      highest shear bond belonged to group 2 (high intensity, 40 s, buccal) and the
      lowest belonged to group 3 (low intensity, 40 s, lingual). Bond strength means in
      control groups were significantly higher than those in experimental groups.
      CONCLUSIONS: In all experimental groups except group 6 (80 s, high intensity,
      lingual), shear bond strength was below the clinically accepted values. In
      clinical limitations where light curing from the same side of the bracket is not
      possible, doubling the curing time and increasing the light intensity during
      trans-illumination are recommended for achieving acceptable bond strengths.

PMID- 24325796
TI  - Mitochondrial permeability transition pore regulates Parkinson's disease
      development in mutant alpha-synuclein transgenic mice.
AB  - Parkinson's disease (PD) is a movement disorder caused by neurodegeneration in
      neocortex, substantia nigra and brainstem, and synucleinopathy. Some inherited PD
      is caused by mutations in alpha-synuclein (alphaSyn), and inherited and
      idiopathic PD is associated with mitochondrial perturbations. However, the
      mechanisms of pathogenesis are unresolved. We characterized a human alphaSyn
      transgenic mouse model and tested the hypothesis that the mitochondrial
      permeability transition pore (mPTP) is involved in the disease mechanisms.
      C57BL/6 mice expressing human A53T-mutant alphaSyn driven by a thymic antigen-1
      promoter develop a severe, age-related, fatal movement disorder involving ataxia,
      rigidity, and postural instability. These mice develop synucleinopathy and
      neocortical, substantia nigra, and cerebello-rubro-thalamic degeneration
      involving mitochondriopathy and apoptotic and non-apoptotic neurodegeneration.
      Interneurons undergo apoptotic degeneration in young mice. Mutant alphaSyn
      associated with dysmorphic neuronal mitochondria and bound voltage-dependent
      anion channels. Genetic ablation of cyclophilin D, an mPTP modulator, delayed
      disease onset, and extended lifespans of mutant alphaSyn mice. Thus, mutant
      alphaSyn transgenic mice on a C57BL/6 background develop PD-like phenotypes, and
      the mPTP is involved in their disease mechanisms. 

PMID- 24325799
TI  - Interaction of microbial sulphate reduction and methanogenesis in oil sands
      tailings ponds.
AB  - Anaerobic turnover of organic compounds in oil sands tailings ponds is
      accomplished by a complex microbial consortium. We examined major electron
      accepting processes in mature fine tailings (MFT). Beside methanogenesis and
      sulphate reduction, microbial iron reduction was an important process of
      anaerobic respiration. Microbial numbers and activity were comparable to those
      reported for natural lakes. To understand metabolic interactions of indigenous
      methanogenic and sulphate-reducing communities, we conducted a 6 month microcosm
      experiment with MFT supplemented with easily available carbon sources and
      molybdate and/or 2-bromoethane sulphonate (BES) as specific inhibitors for
      sulphate reduction and methanogenesis. Methanogenesis increased when microcosms
      were supplemented with extra carbon, but was completely inhibited by the addition
      of BES. Molybdate not only inhibited sulphate reduction, but also methanogenesis,
      indicating a positive relation between the two processes. The turnover of extra
      carbon sources differed between microcosms treated with molybdate and BES.
      Acetate and propionate were not consumed in microcosms amended with molybdate,
      indicating that sulphate-reducing bacteria (SRB) were responsible for their
      metabolisation, and that methane was rather produced by hydrogenotrophic
      methanogens. In microcosms without molybdate, acetate transiently accumulated,
      indicating the activity of both incomplete and complete oxidizing SRB. Ethanol
      and lactate were also consumed in the simultaneous presence of BES and molybdate,
      demonstrating the occurrence of other anaerobic processes. Biomass increased by
      the addition of extra carbon, mainly due to a relative increase in the proportion
      of SRB. The addition of extra carbon lowered the degradation of BTEX compounds.

PMID- 24325798
TI  - Improving the knowledge of amyotrophic lateral sclerosis genetics: novel SOD1 and
      FUS variants.
AB  - Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative
      disorder involving both upper and lower motor neurons. About 5% of all cases
      exhibit signs of frontotemporal degeneration (FTD). We established the mutation
      frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic
      ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all
      originating from the northeastern part of Italy. C9ORF72 pathogenic expansion was
      found on 22% of familial ALS, 5% of sporadic ALS, and 14% of FTD patients,
      resulting the most frequently genetic determinant in our cohort. Sequence
      analysis of ALS cohort identified 2 novel variants on SOD1 (p.Glu41Gly) and FUS
      (p.Gly496Glyfs*31). Interestingly, the single base deletion on FUS was observed
      in an homozygous state, suggesting a recessive pattern of inheritance. No point
      mutations were identified on FTD cohort. Although useful to direct genetic
      testing, this study results expand the current knowledge of ALS genetics. 

PMID- 24325797
TI  - Permeability transition pore-mediated mitochondrial superoxide flashes mediate an
      early inhibitory effect of amyloid beta1-42 on neural progenitor cell
      proliferation.
AB  - Cellular damage by reactive oxygen species and altered neurogenesis are
      implicated in the etiology of AD and the pathogenic actions of amyloid beta
      peptide (Abeta); the underlying mechanisms and the early oxidative intracellular
      events triggered by Abeta are not established. In the present study, we found
      that mouse embryonic cortical neural progenitor cells exhibit intermittent
      spontaneous mitochondrial superoxide (SO) flashes that require transient opening
      of mitochondrial permeability transition pores (mPTPs). The incidence of
      mitochondria SO flash activity in neural progenitor cells (NPCs) increased during
      the first 6-24 hours of exposure to aggregating amyloid beta-peptide (Abeta1-42),
      indicating an increase in transient mPTP opening. Subsequently, the SO flash
      frequency progressively decreased and ceased between 48 and 72 hours of exposure
      to Abeta1-42, during which time global cellular reactive oxygen species
      increased, mitochondrial membrane potential decreased, cytochrome C was released
      from mitochondria and the cells degenerated. Inhibition of mPTPs and selective
      reduction in mitochondrial SO flashes significantly ameliorated the negative
      effects of Abeta1-42 on NPC proliferation and survival. Our findings suggest that
      mPTP-mediated bursts of mitochondrial SO production is a relatively early and
      pivotal event in the adverse effects of Abeta1-42 on NPCs. If Abeta inhibits NPC
      proliferation in the brains of AD patients by a similar mechanism, then
      interventions that inhibit mPTP-mediated superoxide flashes would be expected to
      protect NPCs against the adverse effects of Abeta. 

PMID- 24325800
TI  - Harnessing oil sands microbial communities for use in ex situ naphthenic acid
      bioremediation.
AB  - The caustic hot water extraction process used to release bitumen from the Alberta
      oil sands generates large volumes of tailings waste, or oil sands process water
      (OSPW). OSPW contains several components of environmental concern including
      diluents, polyaromatic hydrocarbons, heavy metals, and naphthenic acids (NAs);
      the latter are of particular concern as they are acutely toxic to aquatic
      organisms and mammals. Studies have demonstrated that the naturally occurring
      OSPW bacteria are capable of metabolizing the NAs. However, this in situ process
      takes place over hundreds of years, and is incomplete, leaving a recalcitrant
      fraction of NAs intact. In this study we explore options for recovering and
      harnessing the naturally occurring OSPW bacteria for potential future use in an
      aerobic ex situ OSPW treatment system. Here we evaluate our recovered microbes on
      their ability to degrade two model NAs, cyclohexane carboxylic acid and
      cyclohexane acetic acid. Using OSPW as a source for a bacterial inoculum, we were
      able to compare single and multispecies OSPW cultures, grown as either a biofilm,
      or as a planktonic suspension. Furthermore, we examined the effect of available
      nutrients on the ability of these cultures to degrade NAs. All biofilms were
      grown using the Calgary Biofilm Device. GC-MS, and GC-FID reveal that
      multispecies biofilm and planktonic cultures are each capable of degrading both
      NAs; a trait not observed for single species cultures. Moreover, complementary
      carbon sources have a tangible effect on the ability of the cultures to initiate
      the degradation of the NAs. 

PMID- 24325801
TI  - Reactive eccrine syringofibroadenomatosis secondary to primary cutaneous
      amyloidosis: a novel association.
AB  - We report the unprecedented case of reactive eccrine syringofibroadenoma (ESFA)
      secondary to primary cutaneous amyloidosis. A 62-year-old woman of Asian
      ethnicity presented with a pruritic rash on the back of long-standing duration.
      Physical examination revealed diffuse hyperpigmentation localized to the
      interscapular region; there were a multitude of hyperpigmented macules merged in
      a rippled pattern intermixed with scattered papules and cobblestone-like areas. A
      punch biopsy from a papule was taken. Histopathological examination revealed a
      network of epithelial strands and cords hanging from the epidermis and harboring
      foci of ductal differentiation. Eosinophilic collections of amorphous material
      were found between the epithelial strands, obscuring the superficial dermis. The
      microscopic picture was consistent with primary cutaneous amyloidosis associated
      with reactive ESFA. Results of histochemical and immunohistochemical staining
      confirmed the diagnosis. We speculate that pathogenetic mechanisms intrinsic to
      primary cutaneous amyloidosis, in addition to unknown genetic factors, resulted
      in clinical changes of lichen amyloidosus associated with an abnormal
      hyperplastic epithelial response with histopathological features of ESFA rather
      than the common epidermal change of acanthosis and hyperkeratosis. 

PMID- 24325802
TI  - Arachnoid cysts in tuberous sclerosis complex.
AB  - OBJECTIVE: Some clinical findings in tuberous sclerosis complex (TSC), such as
      hypomelanotic macules or angiofibromas are related to problems in development of
      the neural crest, which is also the origin of cranial leptomeninges. Arachnoid
      cysts have been reported in two TSC patients to date. The purpose of this study
      was to assess the prevalence and characteristics of arachnoid cysts in a large
      cohort of TSC. MATERIALS AND METHOD: We performed a review of brain MRIs of 220
      TSC patients searching for arachnoid cysts. RESULTS: Arachnoid cysts were found
      in 12 (5.5%) (general population: 0.5%), including ten males (83.3%). Four
      patients (33.3%) had also autosomal dominant polycystic kidney disease (ADPKD)
      due to a contiguous deletion of the TSC2-PKD1 genes. Three patients (25%) had two
      or more arachnoid cysts, of whom two also had ADPKD. One patient with an
      arachnoid cyst did not have tubers, subependymal nodules or white matter
      migration lines. CONCLUSION: Our study suggests that arachnoid cysts are part of
      the clinical spectrum of TSC and may be also present in TSC patients without
      other typical TSC brain lesions.

PMID- 24325803
TI  - Creatine supplementation and oxidative stress in rat liver.
AB  - BACKGROUND: The objective of this study was to determine the effects of creatine
      supplementation on liver biomarkers of oxidative stress in exercise-trained rats.
      METHODS: Forty 90-day-old adult male Wistar rats were assigned to four groups for
      the eight-week experiment. Control group (C) rats received a balanced control
      diet; creatine control group (CCr) rats received a balanced diet supplemented
      with 2% creatine; trained group (T) rats received a balanced diet and intense
      exercise training equivalent to the maximal lactate steady state phase; and
      supplemented-trained (TCr) rats were given a balanced diet supplemented with 2%
      creatine and subjected to intense exercise training equivalent to the maximal
      lactate steady state phase. At the end of the experimental period, concentrations
      of creatine, hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances
      (TBARS) were measured as well as the enzyme activity of superoxide dismutase
      (SOD), glutathione peroxidase (GSH-GPx) and catalase (CAT). Liver tissue levels
      of reduced glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio
      were also determined. RESULTS: Hepatic creatine levels were highest in the CCr
      and TCr groups with increased concentration of H2O2 observed in the T and TCr
      animal groups. SOD activity was decreased in the TCr group. GSH-GPx activity was
      increased in the T and TCr groups while CAT was elevated in the CCr and TCr
      groups. GSH, GGS and the GSH/GSSG ratio did not differ between all animal
      subsets. CONCLUSIONS: Our results demonstrate that creatine supplementation acts
      in an additive manner to physical training to raise antioxidant enzymes in rat
      liver. However, because markers of liver oxidative stress were unchanged, this
      finding may also indicate that training-induced oxidative stress cannot be
      ameliorated by creatine supplementation.

PMID- 24325804
TI  - Interleukin-6: from basic biology to selective blockade of pro-inflammatory
      activities.
AB  - Cytokines receptors exist in membrane bound and soluble form. A soluble form of
      the human IL-6R is generated by limited proteolysis and alternative splicing. The
      complex of IL-6 and soluble IL-6R stimulates target cells not stimulated by IL-6
      alone, since they do not express the membrane bound IL-6R. We have named this
      process trans-signaling. Soluble gp130 is the natural inhibitor of IL-6/soluble
      IL-6R complex responses. Recombinant soluble gp130 protein is a molecular tool to
      discriminate between gp130 responses via membrane bound and soluble IL-6R
      responses. Neutralizing monoclonal antibodies for global blockade of IL-6
      signaling and the sgp130Fc protein for selective blockade of IL-6 trans-signaling
      have been used in several animal models of human diseases. Using the sgp130Fc
      protein or sgp130Fc transgenic mice we demonstrate in models of inflammatory
      bowel disease, peritonitis, rheumatoid arthritis, atherosclerosis pancreatitis,
      colon cancer, ovarian cancer and pancreatic cancer, that IL-6 trans-signaling via
      the soluble IL-6R is the crucial step in the development and the progression of
      the disease. Therefore, sgp130Fc is a novel therapeutic agent for the treatment
      of chronic inflammatory diseases and cancer and it undergoes phase I clinical
      trials as an anti-inflammatory drug since June 2013. 

PMID- 24325805
TI  - Polyphyllin D induces apoptosis in K562/A02 cells through G2/M phase arrest.
AB  - OBJECTIVES: The effect of polyphyllin D on inducing cell death of the K562/A02
      human leukaemia drug-resistant cells in vitro was examined. METHODS: The effect
      of polyphyllin D on K562/A02 cells were analysed by studying their cytotoxicity,
      apoptosis, cell cycle distribution, caspase-3 activity and disruption of
      mitochondrial membrane potential (MMP). KEY FINDINGS: Polyphyllin D, a small
      molecular monomer extracted from rhizoma of Paris polyphyllin, exhibited strong
      anticancer activity in a previous study. Our results demonstrate that polyphyllin
      D exerts a growth inhibitory effect by arresting cells at G2/M phase and by the
      induction of apoptosis in K562/A02 human leukaemia drug-resistant cells, G2/M
      phase arrest was found to be associated with up-regulation of p21 and down
      regulation of cyclin B1 and cyclin-dependent protein kinase 1. Polyphyllin D
      induced apoptosis via the mitochondrial apoptotic pathway as evidenced by
      decreased Bcl-2 expression levels, disruption of MMP and increased Bax,
      cytochrome C and cleaved-caspase-3 levels. CONCLUSIONS: These data suggest that
      polyphyllin D has a potential as a potent therapeutic agent for chronic myeloid
      leukaemia.

PMID- 24325807
TI  - "Malignant" restless legs syndrome. Are we being too harsh with the name?

PMID- 24325806
TI  - Meta-analysis and systematic review of factors biasing the observed prevalence of
      congenitally missing teeth in permanent dentition excluding third molars.
AB  - No meta-analyses or systematic reviews have been conducted to evaluate numerous
      potential biasing factors contributing to the controversial results on
      congenitally missing teeth (CMT). We aimed to perform a rather comprehensive meta
      analysis and systematic review on this subject. A thorough search was performed
      during September 2012 until April 2013 to find the available literature regarding
      CMT prevalence. Besides qualitatively discussing the literature, the meta-sample
      homogeneity, publication bias, and the effects of sample type, sample size,
      minimum and maximum ages of included subjects, gender imbalances, and scientific
      credit of the publishing journals on the reported CMT prevalence were
      statistically analyzed using Q-test, Egger regression, Spearman coefficient,
      Kruskal-Wallis, Welch t test (alpha=0.05), and Mann-Whitney U test (alpha=0.016,
      alpha=0.007). A total of 111 reports were collected. Metadata were heterogeneous
      (P=0.000). There was not a significant publication bias (Egger Regression
      P=0.073). Prevalence rates differed in different types of populations (Kruskal
      Wallis P=0.001). Studies on orthodontic patients might report slightly (about 1%)
      higher prevalence (P=0.009, corrected alpha=0.016). Non-orthodontic dental
      patients showed a significant 2% decline [P=0.007 (Mann-Whitney U)]. Enrolling
      more males in researches might significantly reduce the observed prevalence
      (Spearman rho=-0.407, P=0.001). Studies with higher minimums of subjects' age
      showed always slightly less CMT prevalence. This reached about -1.6% around the
      ages 10 to 13 and was significant for ages 10 to 12 (Welch t test P<0.05). There
      seems to be no limit over the maximum age (Welch t test P>0.2). Studies' sample
      sizes were correlated negatively with CMT prevalence (rho=-0.250, P=0.009). It
      was not verified whether higher CMT rates have better chances of being published
      (rho=0.132, P=0.177). CMT definition should be unified. Samples should be sex
      balanced. Enrolling both orthodontic and dental patients in similar proportions
      might be preferable over sampling from each of those groups. Sampling from
      children over 12 years seems advantageous. Two or more observers should examine
      larger samples to reduce the false negative error tied with such samples.

PMID- 24325808
TI  - "Malignant restless legs syndrome"--a curse or a blessing?

PMID- 24325809
TI  - The role of actigraphy in the assessment of primary insomnia: a retrospective
      study.
AB  - OBJECTIVE: The aim of our study was to evaluate quantitative actigraphic criteria
      obtained using the Actiwatch device (AW64; Cambridge Neurotechnology Ltd.,
      Cambridge, UK) to differentiate participants with insomnia from normal sleepers.
      METHODS: In our retrospective study, we recovered 493 actigraphic records from
      two sleep measure databases of patients with insomnia (n=151) and one of normal
      sleepers (n=342). We considered the following actigraphic sleep parameters: time
      in bed (TIB), sleep-onset latency (SOL), total sleep time (TST), wake after sleep
      onset (WASO), sleep efficiency (SE), number of awakenings (NWAK), terminal
      wakefulness (TWAK), fragmentation index (FI), and mean motor activity (MA). We
      also considered two actigraphic circadian indexes: interdaily stability and
      intradaily variability. Using the Youden index, we calculated the quantitative
      actigraphic criteria that performed best for each actigraphic sleep parameter.
      Finally, we created receiver operating characteristic curves to test the accuracy
      of each criterion identified. RESULTS: All sleep parameters except TST and TWAK
      differentiated the two groups of participants, allowing calculation of
      quantitative actigraphic criteria. There were no differences in the circadian
      indices. CONCLUSIONS: The quantitative actigraphic criteria obtained in our study
      were not the same as those obtained previously with a different device,
      suggesting the need to adopt shared technical solutions for actigraphy.

PMID- 24325810
TI  - Possible causal relationships between competitive swimming in growing age and
      three-dimensional dentoalveolar development.
AB  - BACKGROUND: The aim of this study was to investigate possible links between
      competitive swimming during the growth phase and the development of the
      dentoalveolar arches. METHODS: The study sample included 100 swimmers and a
      control group of 100 age-matched non-swimmers who had never practised swimming or
      related sports. Subjects who had had previous orthodontic treatment were
      excluded. Overjet, overbite, sagittal and transverse parameters, arch dimension,
      crowding and oral habits were recorded. RESULTS: In the swimmers, there was a
      significantly higher frequency of molar symmetry (P=0.04), together with a
      greater number of Class I subjects. The overjet in the swimmers was mainly
      normal, but the arch dimensions were significantly wider (+10% in the upper arch;
      P<0.001). Similarly, the swimmers showed significantly less severe crowding
      (P<0.001) and significantly reduced oral habits (P<0.001). CONCLUSIONS: Our data
      and analysis demonstrate that competitive swimming during the growth phase has a
      favourable effect on dental arch development in the sagittal, vertical and
      transverse planes.

PMID- 24325811
TI  - Assessment of the loading history of patients after high tibial osteotomy using
      SPECT/CT--a new diagnostic tool and algorithm.
AB  - BACKGROUND: Single photon emission computerized tomography and conventional
      computerized tomography (SPECT/CT) tracer uptake has been shown to reflect the
      loading history of the tibiofemoral knee joint and correlate with the mechanical
      and anatomical alignment. It was our primary purpose to develop a novel
      standardized SPECT/CT algorithm for patients undergoing high tibial osteotomy,
      evaluate the inter- and intra-observer reliability (OR), and assess the clinical
      applicability for follow-up of patients before and after high tibial osteotomy.
      METHODS: The localization scheme defines 9 femoral, 8 patellar, and 13 tibial
      zones to accurately map the examined tracer uptake volume in each anatomical area
      of interest. Maximum values for each area (mean +/- standard deviation, median,
      and range) of the localization scheme were recorded as well as normalized values
      for the intensity of SPECT/CT tracer uptake calculated. The inter- and intra-OR
      was assessed for SPECT/CT localization and tracer activity. Pre- and
      postoperative mechanical alignment was assessed in SPECT/CT using a custom-made
      specialized software. The median inter- and intra-observer differences of the
      measured mechanical alignment were calculated along with the inter- and intra-OR.
      RESULTS: The localization scheme showed near-perfect inter- and intra-OR (intra
      class correlation coefficient (ICC) > 0.9) for the measurement of tracer activity
      and localization in all anatomical regions. For measurements of mechanical
      alignment, there was a strong agreement between the two observers (an inter-OR of
      ICC = 0.99 and an intra-OR of ICC = 0.98). CONCLUSIONS: The presented SPECT/CT
      algorithm is highly reliable and clinically feasible. Combined with mechanical
      alignment analysis, it provides the surgeon with helpful information about
      realignment effects of high tibial osteotomies (HTOs) and might help identify the
      optimal personalized degree of correction in HTO surgery.

PMID- 24325812
TI  - Maxillary protraction using a hybrid hyrax-facemask combination.
AB  - BACKGROUND: The aim of this in study was the evaluation of treatment outcomes
      after using a hybrid hyrax-facemask combination in growing class III patients.
      METHODS: Treatment of 16 children (mean age 9.5+/-1.3 years) was investigated
      clinically and by means of pre- and post-treatment cephalograms. Changes in
      sagittal and vertical, and dental and skeletal values were evaluated and tested
      for statistically significant differences. RESULTS: All mini-implants remained
      stable during treatment. Mean treatment duration was 5.8+/-1.7 months. There was
      a significant improvement in skeletal sagittal values: SNA, +2.0 degrees ; SNB, 
      1.2 degrees ; ANB, +3.2 degrees ; WITS appraisal, +4.1 mm and overjet, +2.7 mm.
      No significant changes were found concerning vertical skeletal relationships and
      upper incisor inclination. In relation to A point, the upper first molars moved
      mesially about 0.4 mm (P=0.134). CONCLUSIONS: The hybrid hyrax-facemask
      combination seems to be effective for orthopaedic treatment in growing class III
      patients. Unwanted maxillary dental movements can be avoided due to stable
      skeletal anchorage.

PMID- 24325813
TI  - Facilitation of intraguild prey by its intraguild predator in a three-species
      Lotka-Volterra model.
AB  - Explaining the coexistence of multiple species in the competition and predation
      theatre has proven a great challenge. Traditional intraguild predation (IGP)
      models have only relatively small regions of stable coexistence of all species.
      Here, we investigate potential additional mechanisms that extend these regions of
      stable coexistence. We used a 3-species Lotka-Volterra system to which we added
      an interaction term to model a unidirectional facilitative relationship between
      the two predators in the IGP. In this modelling study the IG predator was able to
      precondition a part of the common resource by an instantaneous manipulation,
      which resulted in the immobilization of the resource species. This mechanism of
      immobilization facilitated the resource uptake by the IG prey and thus increased
      its growth rates even in the presence of the common predator. The facilitative
      relationship of the IG prey by the IG predator produced a stable coexistence of
      both predators even though the IG prey was an inferior competitor for a common
      resource, which cannot be attained with the traditional IGP models. Furthermore,
      our model predicted a 3-species stable coexistence even at high enrichment where
      no coexistence was found in the basic IGP model. Thus, we showed that diversity
      of resource traits could significantly alter emergent community patterns via
      shifts in exploitative competition of IGP-related predators. The described
      mechanism could potentially lead to a higher efficiency in exploitation of common
      resources and thus promote higher diversity in a real community. 

PMID- 24325814
TI  - Epimutation profiling in Beckwith-Wiedemann syndrome: relationship with assisted
      reproductive technology.
AB  - BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder
      associated with abnormalities in 11p15.5 imprinted genes. The most common cause
      is loss of methylation (epimutation) at the imprinting control centre 2
      (IC2/KvDMR1). Most IC2 epimutations occur sporadically but an association with
      conception after assisted reproductive technologies (ART) has been reported. A
      subgroup of IC2 epimutation cases also harbour epimutations at other imprinting
      centres (ICs) outside of 11p15.5. We have investigated the relationship between
      these multiple epimutation cases (ME+), history of ART and clinical phenotype in
      a cohort of 187 BWS IC2 epimutation patients. RESULTS: Methylation analysis at
      PLAGL1, MEST and IGF2R ICs demonstrated an over-representation of patients with
      abnormally low methylation (8.5%, 12% and 6% respectively). At IGF2R some
      patients (2%) had gain of methylation but this was also detected in controls.
      Though there were no significant correlations between the methylation index (MIs)
      at the three ICs tested, a subset of patients appeared to be susceptible to
      multiple epimutations (ME+) and 21.2% of ME + patients had been conceived by ART
      compared to 4.5% (P = 0.0033) without additional epimutations. Methylation array
      profiling (Illumina Goldengate(r)) of patients and controls (excluding 11p15.5
      loci) demonstrated significant differences between patients and controls. No
      significant associations were found between aspects of the BWS phenotype and
      individual epimutations but we describe a case presenting with a post-ART BWS
      like phenotype in which molecular analysis demonstrated loss of paternal allele
      methylation at the 11p15.5 IC1 locus (IC1 regulates imprinting of IGF2 and H19).
      Loss of paternal allele methylation at the IC1 is the molecular finding
      associated with Silver-Russell syndrome whereas BWS is associated with gain of
      maternal allele methylation at IC1. Further analysis demonstrated epimutations at
      PLAGL1 and MEST consistent with the hypothesis that the presence of multiple
      epimutations may be of clinical relevance. CONCLUSIONS: These findings suggest
      that the ME + subgroup of BWS patients are preferentially, but not exclusively,
      associated with a history of ART and that, though at present, there are no clear
      epigenotype-phenotype correlations for ME + BWS patients, non-11p15.5 IC
      epimutations can influence clinical phenotype.

PMID- 24325815
TI  - Non-histone protein HMGB1 inhibits the repair of damaged DNA by cisplatin in NIH
      3T3 murine fibroblasts.
AB  - The nuclear non-histone protein high mobility group box (HMGB) 1 is known to
      having an inhibitory effect on the repair of DNA damaged by the antitumor drug
      cisplatin in vitro. To investigate the role of HMGB1 in living cells, we studied
      the DNA repair of cisplatin damages in mouse fibroblast cell line, NIH-3T3. We
      evaluated the effect of the post-synthetic acetylation and C-terminal domain of
      the protein by overexpression of the parental and mutant GFP fused forms of
      HMGB1. The results revealed that HMGB1 had also an inhibitory effect on the
      repair of cisplatin damaged DNA in vivo. The silencing of HMGB1 in NIH-3T3 cells
      increased the cellular DNA repair potential. The increased levels of repair
      synthesis could be "rescued" and returned to less than normal levels if the
      knockdown cells were transfected with plasmids encoding HMGB1 and HMGB1 K2A. In
      this case, the truncated form of HMGB1 also exhibited a slight inhibitory effect.
      [BMB Reports 2016; 49(2): 99-104]. 

PMID- 24325816
TI  - The expression and secretion of vimentin in the progression of non-alcoholic
      steatohepatitis.
AB  - The pathogenesis of non-alcoholic steatohepatitis (NASH) is not fully understood.
      In the present study, both in vitro and in vivo vimentin expression and secretion
      in NASH were investigated. The exposure of palmitate and lipopolysaccharide (LPS)
      to HepG2 cells enhanced caspase-3 activity and vimentin expression, respectively.
      The combined effects of both treatments on vimentin expression and caspase-3
      activation appeared to be synergic. In contrast, blockade of caspase-3 activity
      by zVADfmk resulted in a significant reduction of cleaved vimentin and secreted
      vimentin into the culture supernatant. Similarly, lipid accumulation and
      inflammation occurred in mice fed a methionine-choline-deficient diet; thus,
      vimentin expression and serum cleaved vimentin levels were increased. However,
      vimentin was not significantly upregulated, and no cleavage occurred in mice fed
      a high-fat diet. It was conclusively determined that lipid accumulation in
      hepatocytes induces apoptosis through a caspase-3 dependent pathway; whereas, LPS
      stimulates vimentin expression, leading to its cleavage and secretion. Increased
      vimentin fragment levels indicated the existence of substantial hepatocellular
      death via an apoptotic mechanism.

PMID- 24325817
TI  - Neurofeedback: introduction to the special issue.

PMID- 24325818
TI  - Hepatitis B virus surface antigen seroconversion in HIV-infected individual after
      pegylated interferon-alpha treatment: a case report.
AB  - Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals.
      Concurrent HIV/HBV infection occurs due to the overlapping routes of
      transmission, particularly sexual and parenteral. HIV-infected patients that have
      acute hepatitis B have six times greater risk of developing chronic hepatitis B,
      with higher viral replication, rapid progression to end-stage liver disease and
      shorter survival. The coinfection is also associated with poor response to
      hepatitis B treatment with interferon-alpha and increased liver toxicity to the
      antiretroviral therapy. Herein, we describe the case of a 35-year-old man who
      engages in sex with men and presented with newly diagnosed HIV-1, serological
      markers for acute hepatitis B and progression to chronic hepatitis B infection
      (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis
      as indicated by liver biopsy). Lacking indication of antiretroviral treatment
      (CD4 768 cells/mm3), he was treated with pegylated-interferon alpha2b (1.5
      mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment,
      the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks,
      he presented HBsAg seroconversion to anti-HBs. One year after treatment, the
      patient maintained sustained virological response (undetectable HBV-DNA). The
      initiation of antiretroviral therapy with nucleosides and nucleotides is
      recommended earlier for coinfected individuals. However, this report emphasizes
      that pegylated interferon remains an important therapeutic strategy to be
      considered for selected patients, in whom the initiation of HAART may be delayed.

PMID- 24325819
TI  - Demonstration of the efficiency and robustness of an acid leaching process to
      remove metals from various CCA-treated wood samples.
AB  - In recent years, an efficient and economically attractive leaching process has
      been developed to remove metals from copper-based treated wood wastes. This study
      explored the applicability of this leaching process using chromated copper
      arsenate (CCA) treated wood samples with different initial metal loading and
      elapsed time between wood preservation treatment and remediation. The sulfuric
      acid leaching process resulted in the solubilization of more than 87% of the As,
      70% of the Cr, and 76% of the Cu from CCA-chips and in the solubilization of more
      than 96% of the As, 78% of the Cr and 91% of the Cu from CCA-sawdust. The results
      showed that the performance of this leaching process might be influenced by the
      initial metal loading of the treated wood wastes and the elapsed time between
      preservation treatment and remediation. The effluents generated during the
      leaching steps were treated by precipitation-coagulation to satisfy the
      regulations for effluent discharge in municipal sewers. Precipitation using
      ferric chloride and sodium hydroxide was highly efficient, removing more than 99%
      of the As, Cr, and Cu. It appears that this leaching process can be successfully
      applied to remove metals from different CCA-treated wood samples and then from
      the effluents. 

PMID- 24325820
TI  - A model for evaluating the environmental benefits of elementary school
      facilities.
AB  - In this study, a model that is capable of evaluating the environmental benefits
      of a new elementary school facility was developed. The model is composed of three
      steps: (i) retrieval of elementary school facilities having similar
      characteristics as the new elementary school facility using case-based reasoning;
      (ii) creation of energy consumption and material data for the benchmark
      elementary school facility using the retrieved similar elementary school
      facilities; and (iii) evaluation of the environmental benefits of the new
      elementary school facility by assessing and comparing the environmental impact of
      the new and created benchmark elementary school facility using life cycle
      assessment. The developed model can present the environmental benefits of a new
      elementary school facility in terms of monetary values using Environmental
      Priority Strategy 2000, a damage-oriented life cycle impact assessment method.
      The developed model can be used for the following: (i) as criteria for a green
      building rating system; (ii) as criteria for setting the support plan and size,
      such as the government's incentives for promoting green-building projects; and
      (iii) as criteria for determining the feasibility of green building projects in
      key business sectors. 

PMID- 24325821
TI  - Response of an invasive native wetland plant to environmental flows: implications
      for managing regulated floodplain ecosystems.
AB  - The natural flow regimes of rivers underpin the health and function of floodplain
      ecosystems. However, infrastructure development and the over-extraction of water
      has led to the alteration of natural flow regimes, resulting in the degradation
      of river and floodplain habitats globally. In many catchments, including
      Australia's Murray-Darling Basin, environmental flows are seen as a potentially
      useful tool to restore natural flow regimes and manage the degradation of rivers
      and their associated floodplains. In this paper, we investigated whether
      environmental flows can assist in controlling an invasive native floodplain plant
      in Barmah Forest, south-eastern Australia. We experimentally quantified the
      effects of different environmental flow scenarios, including a shallow (20 cm)
      and deeper (50 cm) flood of different durations (12 and 20 weeks), as well as
      drought and soil-saturated conditions, on the growth and survival of seedlings of
      Juncus ingens, a native emergent macrophyte that has become invasive in some
      areas of Barmah Forest following river regulation and alteration of natural flow
      regimes. Three height classes of J. ingens (33 cm, 17 cm and 12 cm) were included
      in the experiment to explicitly test for relationships between treatments, plant
      survival and growth, and plant height. We found that seedling mortality occurred
      in the drought treatment and in the 20-week flood treatments of both depths;
      however, mortality rates in the flood treatments depended on initial plant
      height, with medium and short plants (initial heights of <=17 cm) exhibiting the
      highest mortality rates. Both the 20 cm and 50 cm flood treatments of only 12
      weeks duration were insufficient to cause mortality in any of the height classes;
      indeed, shoots of plants in the 20 cm flood treatment were able to elongate
      through the water surface at rapid rates. Our findings have important
      implications for management of Barmah Forest and floodplain ecosystems elsewhere,
      as it demonstrates the potential for using environmental flows to limit the
      spread of invasive plants by targeting a life-stage that is particularly
      sensitive to prolonged submergence. However, there may be narrow thresholds
      between the conditions that provide effective control of an invasive species, and
      those that instead facilitate growth and may promote further invasion. 

PMID- 24325822
TI  - Cost-effective river rehabilitation planning: optimizing for morphological
      benefits at large spatial scales.
AB  - River rehabilitation aims to protect biodiversity or restore key ecosystem
      services but the success rate is often low. This is seldom because of
      insufficient funding for rehabilitation works but because trade-offs between
      costs and ecological benefits of management actions are rarely incorporated in
      the planning, and because monitoring is often inadequate for managers to learn by
      doing. In this study, we demonstrate a new approach to plan cost-effective river
      rehabilitation at large scales. The framework is based on the use of cost
      functions (relationship between costs of rehabilitation and the expected
      ecological benefit) to optimize the spatial allocation of rehabilitation actions
      needed to achieve given rehabilitation goals (in our case established by the
      Swiss water act). To demonstrate the approach with a simple example, we link
      costs of the three types of management actions that are most commonly used in
      Switzerland (culvert removal, widening of one riverside buffer and widening of
      both riversides) to the improvement in riparian zone quality. We then use Marxan,
      a widely applied conservation planning software, to identify priority areas to
      implement these rehabilitation measures in two neighbouring Swiss cantons
      (Aargau, AG and Zurich, ZH). The best rehabilitation plans identified for the two
      cantons met all the targets (i.e. restoring different types of morphological
      deficits with different actions) rehabilitating 80,786 m (AG) and 106,036 m (ZH)
      of the river network at a total cost of 106.1 Million CHF (AG) and 129.3 Million
      CH (ZH). The best rehabilitation plan for the canton of AG consisted of more and
      better connected sub-catchments that were generally less expensive, compared to
      its neighbouring canton. The framework developed in this study can be used to
      inform river managers how and where best to spend their rehabilitation budget for
      a given set of actions, ensures the cost-effective achievement of desired
      rehabilitation outcomes, and helps towards estimating total costs of long-term
      rehabilitation activities. Rehabilitation plans ready to be implemented may be
      based on additional aspects to the ones considered here, e.g., specific cost
      functions for rural and urban areas and/or for large and small rivers, which can
      simply be added to our approach. Optimizing investments in this way will
      ultimately increase the likelihood of on-ground success of rehabilitation
      activities. 

PMID- 24325823
TI  - Measurement of flood peak effects as a result of soil and land management, with
      focus on experimental issues and scale.
AB  - As a result of several serious flood events which have occurred since 2000,
      flooding across Europe is now receiving considerable public and media attention.
      The impact of land use on hydrology and flood response is significantly under
      researched, and the links between land use change and flooding are still unclear.
      This study considers runoff data available from studies of arable in-field land
      use management options, applied with the aim of reducing diffuse pollution from
      arable land, in order to investigate whether these treatments also have potential
      to reduce downstream flooding. Intensive monitoring of 17 hillslope treatment
      areas produced a record of flood peak data covering different mitigation
      treatments for runoff which occurred in the winter of 2007-2008. We investigated
      event total runoff responses to rainfall, peak runoff, and timing of the runoff
      peaks from replicates of different treatments, in order to assess whether there
      is a significant difference in flood peak response between different mitigation
      options which could be used to mitigate downstream flood risk. A mixed-modelling
      approach was adopted in order to determine whether differences observed in runoff
      response were significant. The results of this study suggest that changes in land
      use management using arable in-field mitigation treatments can affect local-scale
      runoff generation, with differences observed in the size, duration and timing of
      flood peaks as a result of different management practices, but the study was
      unable to allow significant treatment effects to be determined. We suggest that
      further field studies of the effects of changes in land use and land use
      management need to upscale towards farm and catchment scale experiments which
      consider high quality before-and-after data over longer temporal timescales. This
      type of data collection is essential in order to allow appropriate land use
      management decisions to be made. 

PMID- 24325824
TI  - Use of preoperative computed tomography for surgical treatment of recurrent
      draining tracts.
AB  - OBJECTIVES: To evaluate a rational decision-making approach based on preoperative
      computed tomography for surgical planning in dogs and cats with recurrent
      draining tracts. METHODS: Retrospective evaluation of case records of animals
      that underwent preoperative computed tomography for surgical treatment of
      thoracic/abdominal recurrent draining tracts. Cases were classified according to
      whether a source of inflammation and/or infection, in particular foreign bodies,
      was identified (group 1), suspected (group 2) or neither identified nor suspected
      (group 3) at computed tomography. Surgery consisted of removal of the source of
      inflammation and/or infection (group 1), debridement or abscess drainage (group
      2) or en bloc resection of diseased tissues (group 3). Clinical outcome was
      evaluated at least 12 months after surgery. RESULTS: A source of inflammation
      and/or infection was found in 100% (8 of 8), 41% (7 of 17) and 25% (3 of 12) of
      cases in groups 1, 2 and 3, respectively. Recurrent draining tracts resolved in
      100% (8 of 8), 94% (16 of 17) and 92% (11 of 12) of cases in groups 1, 2 and 3,
      respectively. CLINICAL SIGNIFICANCE: The proposed strategy provided a 95% (35 of
      37) cure rate, after a single procedure in 81% (30 of 37) of cases. Recovery of a
      foreign body at surgery was not a prerequisite for the resolution of the
      recurrent draining tracts.

PMID- 24325825
TI  - Perceptions of dental professionals and laypeople to altered dental esthetics in
      cases with congenitally missing maxillary lateral incisors.
AB  - BACKGROUND: The smile perception of patients is not strictly related to
      standardized protocols and technical implications which certainly affect
      clinicians' decisions. The absence of maxillary lateral incisors could affect
      smile esthetics either with treatment or not. The aim of the present study was to
      investigate if different perceptions on altered smiles due to missing maxillary
      lateral incisors, with or without treatment, exist among different groups of
      people (laypersons, adult orthodontic patients, general dentists, and
      orthodontists). METHODS: An ideal smile model was selected and altered simulating
      different malocclusions and treatment options. Twelve simulations were submitted
      to four categories of respondents: laypeople, adult orthodontic patients, general
      dentists and orthodontists. They were asked to express smile perception for each
      simulation by ranking and rating simulations using a 0 to 100 visual analog
      scale. Analysis of variance was used to determine if there were statistically
      significant differences in values assigned among the four categories of
      respondents for each simulation. RESULTS: Significant differences in smile
      perceptions were found between professionals (dentists and orthodontists) and
      laypeople. Presence of dental tipping and marked diastema in the arch were
      disharmonious aspects less tolerated in a smile by all categories of evaluators.
      Simulations associated with space closure orthodontic treatment were ranked as
      the most attractive smile and significantly ranked higher by dental professionals
      than patients and laypeople. CONCLUSIONS: Treatment, absence of diastema, and
      symmetry were the most accepted characteristics by all categories of respondents.
      Ideal orthodontic treatment options might be overestimated by clinicians when
      compared to laypeople's smile perception.

PMID- 24325826
TI  - Type I interferon-dependent activation of NK cells by rAd28 or rAd35, but not
      rAd5, leads to loss of vector-insert expression.
AB  - Vaccines constructed from rare-serotype recombinant adenovirus vectors (rAd) such
      as rAd serotype 28 (rAd28) and rAd35 are currently being explored as alternatives
      to rAd5-based vaccines because they circumvent the problems with pre-existing
      immunity that complicate the effectiveness of rAd5 vaccines. However, previous
      work has demonstrated that the immunogenicity of rAd28 and rAd35 is substantially
      lower than rAd5. Here we show that rAd28 and rAd35 increase apoptosis of antigen
      presenting cells (APCs), such as monocytes, relative to rAd5 and mock infected
      controls. APCs undergoing apoptosis showed an increased loss of vector-insert
      expression. Loss of vector-insert expression correlated with activation of NK
      cells, which resulted in apoptosis of co-cultured monocytes. Finally, we show
      that activation of NK cells is dependent on IFNalpha which is produced by
      exposure to rAd28 or rAd35, but not to rAd5. Taken together, these data
      demonstrate that IFNalpha-induced activation of NK cells leads to increased
      monocyte apoptosis and subsequent vector-insert loss. This may be a possible
      mechanism that results in reduced immunogenicity of rAd28 and rAd35-based
      vectors. 

PMID- 24325827
TI  - Co-administration of live measles and yellow fever vaccines and inactivated
      pentavalent vaccines is associated with increased mortality compared with measles
      and yellow fever vaccines only. An observational study from Guinea-Bissau.
AB  - BACKGROUND: Studies from low-income countries indicate that co-administration of
      inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated
      measles vaccine (MV) is associated with increased mortality compared with
      receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine is
      replacing DTP in many low-income countries and yellow fever vaccine (YF) has been
      introduced to be given together with MV. Pentavalent and YF vaccines were
      introduced in Guinea-Bissau in 2008. We investigated whether co-administration of
      pentavalent vaccine with MV and yellow fever vaccine has similar negative
      effects. METHODS: In 2007-2011, we conducted a randomised placebo-controlled
      trial of vitamin A at routine vaccination contacts among children aged 6-23
      months in urban and rural Guinea-Bissau. In the present study, we included 2331
      children randomised to placebo who received live vaccines only (MV or MV+YF) or a
      combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent).
      Mortality was compared in Cox proportional hazards models stratified for
      urban/rural enrolment adjusted for age and unevenly distributed baseline factors.
      RESULTS: While DTP was still used 685 children received MV only and 358 MV+DTP;
      following the change in programme, 940 received MV+YF only and 348
      MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate
      ratio (MRR) for co-administered live and inactivated vaccines compared with live
      vaccines only was 3.24 (1.20-8.73). For MV+YF+pentavalent compared with MV+YF
      only, the adjusted MRR was 7.73 (1.79-33.4). CONCLUSION: In line with previous
      studies of DTP, the present results indicate that pentavalent vaccine co
      administered with MV and YF is associated with increased mortality.

PMID- 24325828
TI  - Course fees and academic ranking: insights from the IMI EMTRAIN on-course(r)
      database.
AB  - The Innovative Medicines Initiative (IMI) funded project on-course(r)
      (http://www.on-course.eu/) lists postgraduate biomedical courses in Europe and is
      comprehensive for all taught and research master's courses. Using on-course(r),
      new insights into education and training in Europe can be delivered; and here we
      investigate the relationship between master's course fees and university ranking.
      We hypothesise that higher master's course fees would be associated with higher
      university ranking. This was indeed the case for research master's courses and
      for taught master's courses for non-EU students. However, we observed no
      correlation between taught master's course fees for EU students and university
      ranking, meaning EU students are paying on average as much for courses at lower
      ranked universities as they are for courses at higher ranked universities.

PMID- 24325829
TI  - Development of a method for the analysis of drugs of abuse in vitreous humor by
      capillary electrophoresis with diode array detection (CE-DAD).
AB  - This work presents the development of an analytical method based on capillary
      electrophoresis with diode array detection for the analysis of drugs of abuse and
      biotransformation products in vitreous humor. Composition of the background
      electrolyte, implementation of an online pre-concentration strategy and sample
      preparation procedures were objects of study. The complete electrophoretic
      separation of 12 analytes (amphetamine, methamphetamine, 3,4
      methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4
      methylenedioxyethylamphetamine (MDEA), ketamine, cocaine, cocaethylene,
      lidocaine, morphine, 6-monoacetylmorphine and heroin) and the internal standard N
      methyl-1-(3,4-methylenedioxyphenyl)-2-butamine (MBDB) was obtained within 13min
      of run. The method was validated presenting good linearity (r(2)>0.99), recovery
      >=90%, precision better than 12% RSD and acceptable accuracy in the range of 86
      118% at three concentration levels (50, 100 and 500ng/mL). LODs and LOQs in the
      order of 1-5ng/mL and 5-10ng/mL, respectively, were obtained. After validation,
      the method was applied to eighty-seven vitreous humor samples and the results
      were compared to those obtained by a liquid chromatography tandem mass
      spectrometry (LC-MS/MS) screening method, routinely used by the forensic
      toxicology laboratory of the Sao Paulo State Police, Brazil. Cocaine was detected
      in 7.1%, cocaethylene in 3.6%, lidocaine in 2.4% and ketamine in 1.2% of the
      total number of analyzed samples. 

PMID- 24325830
TI  - Comparative chromatography-mass spectrometry studies on the antiretroviral drug
      nevirapine-analytical performance characteristics in human plasma determination.
AB  - A contrast between the analytical performance characteristics using gas
      chromatography-mass spectrometry (GC-MS) liquid chromatography-mass spectrometry
      (LC-MS) and liquid chromatography-ultraviolet (LC-UV) detection for the
      determination of the antiretroviral drug (ARV) nevirapine (NVP) in fortified
      human plasma after QuEChERS extraction has been made. Analytical performance
      characteristics, i.e. linearities, instrument detection limits (IDLs), limits of
      quantitation (LOQs), method detection limits (MDLs), % mean recoveries and the
      corresponding relative standard deviations (%RSDs) were estimated using
      techniques above. Using GC-MS, the correlation coefficients (r(2)) were >=0.990,
      which were deemed acceptable linearities. The MDLs ranged between 11.1-29.8MUg/L
      and 13.7-36.0MUg/L using helium and hydrogen carrier gases respectively. The LOQs
      ranged between 16.5-66.7MUg/L and 28.4-98.7MUg/L using helium and hydrogen
      carrier gases respectively with a % mean recovery of 83% and %RSD of 4.6%. Using
      LC-MS and LC-UV, the correlation coefficients (r(2)) were >=0.990. The MDLs were
      ranged between 3.14 and 47.1MUg/L. The LOQs ranged between 2.85 and 90.0MUg/L
      respectively. The MDLs using GC-MS, LC-MS and LC-UV were below the therapeutic
      range for NVP in human plasma is considered to be between 2300MUg/L (Cmin) and
      8000MUg/L (Cmax). This study also demonstrated that helium can be substituted
      with hydrogen which is relatively cheaper and easily obtainable even by use of a
      generator. 

PMID- 24325831
TI  - Rationale, bench testing and in vivo evaluation of a novel 5 mm laparoscopic
      vessel sealing device with homogeneous pressure distribution in long instrument
      jaws.
AB  - BACKGROUND: In 1998, an electrothermal bipolar vessel sealing (EBVS) system was
      introduced and quickly became an integral component of the surgical armamentarium
      in various surgical specialties. Currently available EBVS instruments use a
      scissor-like jaw configuration and closing mechanism, which causes decreasing
      compression pressure from the proximal to the distal end of the jaws. A new EBVS
      system is described here which utilizes a different instrument jaw configuration
      and closing mechanism to enable a more homogeneous pressure distribution despite
      longer instrument jaws. METHODS: Results of jaw pressure distribution
      measurements as well as sealing experiments with subsequent burst pressure
      measurements ex vivo on bovine uterine arteries are demonstrated. Furthermore, an
      in vivo evaluation of the new EBVS system in a canine and porcine model including
      histological examination is presented. RESULTS: The device revealed an even
      pressure distribution throughout the whole jaw length. The ex vivo burst pressure
      measurements revealed high average burst pressures, above 300 mmHg, independent
      of the outer diameter (1 to 7 mm) of the tested vessels. Histological evaluation
      of sealed vessels 21 days postoperatively demonstrated sealed and fused vessels
      without adjacent tissue damage. CONCLUSIONS: The even pressure distribution
      leading to a sufficient tissue sealing in combination with the novel closing
      mechanism and extended jaw length differentiates the novel device from other
      available EBVS systems. This might offer a reduction of the overall procedure
      time, which should be further evaluated in a clinical study.

PMID- 24325832
TI  - Skeletal and dental effects produced by functional regulator-2 in pre-pubertal
      class II patients: a controlled study.
AB  - BACKGROUND: Whether skeletal effects are obtained by functional appliances in
      class II subjects is still controversial. In this regard, most of the available
      studies did not clearly identify the growth phases (i.e. pubertal or not) of the
      treated patients. This retrospective controlled study aimed at evaluating the
      skeletal and dental changes in class II subjects produced by the functional
      regulator (FR)-2 treatment during the pre-pubertal growth phase. METHODS: The
      data were derived from records obtained at a university dental clinic. A total of
      17 treated subjects and a total of 17 untreated controls, all pre-pubertal,
      matched for malocclusion, age (8.8+/-1.5 years) and sex (18 females, 16 males),
      were included. The overall observational period was 1.6+/-0.8 years for both
      groups. RESULTS: Only minor skeletal changes with very little clinical relevance
      were seen after the observational period. Most of the changes produced by the FR
      2 treatment were at the dental level including palatal tipping of the maxillary
      incisors and slight proclination of the mandibular incisors, both accounting for
      the noteworthy overjet reduction. CONCLUSIONS: The present study has shown that
      functional treatment of class II malocclusion by FR-2 appliance during the pre
      pubertal growth phase is limited to modification at the dental level.

PMID- 24325833
TI  - Sporadic desmoid-type fibromatosis: a stepwise approach to a non-metastasising
      neoplasm--a position paper from the Italian and the French Sarcoma Group.
AB  - Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal
      proliferation of myofibroblasts lacking metastatic capacity. It may be observed
      in nearly every part of the body. Considering the variable clinical
      presentations, anatomic locations, and biologic behaviors, an individualized
      treatment approach is required. The pathogenesis of DF is not completely
      understood even if a high prevalence (~85%) of CTNNB1 mutations discovered in
      sporadic DF underlies the importance of the Wnt/beta-catenin pathway. No
      established and evidence-based approach for the treatment of this neoplasm is
      available as of today. Considering the unpredictable behavior and the
      heterogeneity of this disease, we propose a treatment algorithm approved by the
      French and the Italian Sarcoma Group, based on a front-line wait and see approach
      and subsequent therapy in the case of progression. A careful counseling at a
      referral center is mandatory and should be offered to all patients affected by
      sporadic DF from the time of their diagnosis. 

PMID- 24325834
TI  - Comparison of the effects of ibuprofen and acetaminophen on PGE2 levels in the
      GCF during orthodontic tooth movement: a human study.
AB  - BACKGROUND: Pain is among the most cited negative effects of orthodontic
      treatment. Non-steroidal anti-inflammatory drugs seem to be an effective option
      for minimizing this but can have adverse effects on tooth movement owing to their
      ability to block prostaglandin synthesis. Acetaminophen has been suggested as the
      analgesic of choice during orthodontic treatment as it showed no effect on
      orthodontic tooth movement in previous animal studies. The purpose of this study
      was to compare the effects of ibuprofen and acetaminophen on the prostaglandin E2
      (PGE2) levels of the gingival crevicular fluid (GCF) during orthodontic tooth
      movement in human subjects. METHODS: A total of 42 patients (mean age 18+/-4.5
      years) were randomly divided into three equal groups: ibuprofen, acetaminophen,
      and control groups. Maxillary canines were distalized with 150 g of force
      delivered by NiTi coil springs. GCF samples were obtained before (baseline) and
      after spring activation at 24, 48, and 168 h. The PGE2 content of the GCF was
      determined using enzyme-linked immunosorbent assay. RESULTS: PGE2 levels in all
      groups increased significantly by 24 and 48 h of force application and decreased
      to baseline levels by 168 h. No significant difference was found between the
      acetaminophen and control groups at any time point. There was a significant
      decrease in PGE2 levels in the ibuprofen group at 24 and 48 h when compared to
      the other two groups. CONCLUSIONS: Acetaminophen showed no significant effect on
      prostaglandin synthesis and may be the safe choice compared to ibuprofen for
      relieving pain associated with orthodontic tooth movement.

PMID- 24325835
TI  - Comparative preclinical pharmacokinetics study of 3,3'-diindolylmethane
      formulations: is personalized treatment and targeted chemoprevention in the
      horizon?
AB  - BACKGROUND: 3,3'-Diindolylmethane (DIM) is known as an agent of natural origin
      that provides protection against different cancers due to the broad spectrum of
      its biological activities in vivo. However, this substance has a very poor
      biodistribution and absorption in animal tissues. This preclinical trial was
      conducted to evaluate the pharmacokinetics and bioavailability of various DIM
      formulations in animal model. MATERIALS AND METHODS: The pharmacokinetic
      parameters of one crystalline DIM formulation and one liquid DIM formulation (oil
      solution) compared to non-formulated crystalline DIM (control) were tested in 200
      rats. The formulations were orally administered to animals by gavage at doses of
      200 mg/kg per DIM (crystalline DIM formulation and non-formulated crystalline
      DIM) and 0.1 mg/kg per DIM (DIM in oil solution). DIM plasma elimination was
      measured using HPLC method; after that, the area under the curve (AUC), relative
      bioavailability, and absolute bioavailability were estimated for two formulations
      in relation to non-formulated crystalline DIM. RESULTS AND CONCLUSION: The
      highest bioavailability was achieved by administering liquid DIM (oil solution),
      containing cod liver oil and polysorbate. The level of DIM in rat blood plasma
      was about fivefold higher, though the 2,000-fold lower dose was administered
      compared to crystalline DIM forms. The novel pharmacological DIM substance with
      high bioavailability may be considered as a promising targeted antitumor
      chemopreventive agent. It could be used to prevent breast and ovarian cancer
      development in patients with heterozygous inherited and sporadic BRCA1 gene
      mutations. Further preclinical and clinical trials are needed to prove this
      concept.

PMID- 24325836
TI  - Minocycline prevents retinal inflammation and vascular permeability following
      ischemia-reperfusion injury.
AB  - BACKGROUND: Many retinal diseases are associated with vascular dysfunction
      accompanied by neuroinflammation. We examined the ability of minocycline (Mino),
      a tetracycline derivative with anti-inflammatory and neuroprotective properties,
      to prevent vascular permeability and inflammation following retinal ischemia
      reperfusion (IR) injury, a model of retinal neurodegeneration with breakdown of
      the blood-retinal barrier (BRB). METHODS: Male Sprague-Dawley rats were subjected
      to 45 min of pressure-induced retinal ischemia, with the contralateral eye
      serving as control. Rats were treated with Mino prior to and following IR. At 48
      h after reperfusion, retinal gene expression, cellular inflammation, Evan's blue
      dye leakage, tight junction protein organization, caspase-3 activation, and DNA
      fragmentation were measured. Cellular inflammation was quantified by flow
      cytometric evaluation of retinal tissue using the myeloid marker CD11b and
      leukocyte common antigen CD45 to differentiate and quantify CD11b+/CD45low
      microglia, CD11b+/CD45hi myeloid leukocytes and CD11bneg/CD45hi lymphocytes.
      Major histocompatibility complex class II (MHCII) immunoreactivity was used to
      determine the inflammatory state of these cells. RESULTS: Mino treatment
      significantly inhibited IR-induced retinal vascular permeability and disruption
      of tight junction organization. Retinal IR injury significantly altered mRNA
      expression for 21 of 25 inflammation- and gliosis-related genes examined. Of
      these, Mino treatment effectively attenuated IR-induced expression of lipocalin 2
      (LCN2), serpin peptidase inhibitor clade A member 3 N (SERPINA3N), TNF receptor
      superfamily member 12A (TNFRSF12A), monocyte chemoattractant-1 (MCP-1, CCL2) and
      intercellular adhesion molecule-1 (ICAM-1). A marked increase in leukostasis of
      both myeloid leukocytes and lymphocytes was observed following IR. Mino treatment
      significantly reduced retinal leukocyte numbers following IR and was particularly
      effective in decreasing the appearance of MHCII+ inflammatory leukocytes.
      Surprisingly, Mino did not significantly inhibit retinal cell death in this
      model. CONCLUSIONS: IR induces a retinal neuroinflammation within hours of
      reperfusion characterized by inflammatory gene expression, leukocyte adhesion and
      invasion, and vascular permeability. Despite Mino significantly inhibiting these
      responses, it failed to block neurodegeneration.

PMID- 24325837
TI  - Analysis of the characteristics of slot design affecting resistance to sliding
      during active archwire configurations.
AB  - BACKGROUND: During orthodontic treatment, a low resistance to slide (RS) is
      desirable when sliding mechanics are used. Many studies showed that several
      variables affect the RS at the bracket-wire interface; among these, the design of
      the bracket slot has not been deeply investigated yet. This study aimed to
      clarify the effect of different slot designs on the RS expressed by five types of
      low-friction brackets in vertical and horizontal active configurations of the
      wire. METHODS: Five low-friction brackets (Damon SL II, Ormco, Orange, CA, USA;
      In-Ovation, GAC International, Bohemia, NY, USA; Quick, Forestadent, Pforzheim,
      Germany; Time 2, AO, Sheboygan, WI, USA; Synergy, RMO, Denver, CO, USA) coupled
      with an 0.014-in NiTi thermal wire (Therma-Lite, AO) were tested in two three
      bracket experimental models simulating vertical and horizontal bracket
      displacements. A custom-made machine was used to measure frictional resistance
      with tests repeated on ten occasions for each bracket-wire combination. Design
      characteristics such as the mesio-distal slot width, slot depth, and presence of
      chamfered edges at the extremities of the slot were evaluated on SEM images
      (SUPRA, Carl Zeiss, Oberkochen, Germany) and analyzed in relation to the data of
      RS recorded. RESULTS: Time 2 was found to show the higher frictional forces (1.50
      and 1.35 N) in both experimental models (p<0.05), while Quick and Synergy
      brackets showed the lower frictional values in the vertical (0.66 N) and in the
      horizontal (0.68 N) bracket displacements, respectively. With vertically
      displaced brackets, the increased mesio-distal slot width and the presence of
      clear angle at mesial and distal slot edges increase the values of RS. With
      brackets horizontally displaced, the RS expressed by the wire is influenced
      simultaneously by the depth of the slot, the mesio-distal slot width, and the
      presence of clear angle at the extremities of the slot base, the clip, or the
      slide. CONCLUSION: In order to select the proper low-friction bracket system,
      clinicians should consider specific characteristics of slot design apart from the
      wire engaging method.

PMID- 24325838
TI  - Neuronal aging: learning from C. elegans.
AB  - The heterogeneity and multigenetic nature of nervous system aging make modeling
      of it a formidable task in mammalian species. The powerful genetics, simple
      anatomy and short life span of the nematode Caenorhabditis elegans offer unique
      advantages in unraveling the molecular genetic network that regulates the
      integrity of neuronal structures and functions during aging. In this review, we
      first summarize recent breakthroughs in the morphological and functional
      characterization of C. elegans neuronal aging. Age-associated morphological
      changes include age-dependent neurite branching, axon beading or swelling, axon
      defasciculation, progressive distortion of the neuronal soma, and early decline
      in presynaptic release function. We then discuss genetic pathways that modulate
      the speed of neuronal aging concordant with alteration in life span, such as
      insulin signaling, as well as cell-autonomous factors that promote neuronal
      integrity during senescence, including membrane activity and JNK/MAPK signaling.
      As a robust genetic model for aging, insights from C. elegans neuronal aging
      studies will contribute to our mechanistic understanding of human brain aging. 

PMID- 24325839
TI  - Evaluation of tip and torque on virtual study models: a validation study.
AB  - BACKGROUND: The objectives of this study were to develop and validate a novel
      analysis protocol to measure linear and angular measurements of tip and torque of
      each tooth in the dental arches of virtual study models. METHODS: Maxillary and
      mandibular dental casts of 25 subjects with a full permanent dentition were
      scanned using a three-dimensional model scanner. Sixty points per arch were
      digitized on each model, five points on each tooth. A custom analysis to measure
      linear distances and angles of tip and torque was developed using a new reference
      plane passing as a best-fit among all of the lingual gingival points, with the
      intermolar lingual distance set as the reference X-axis. The linear distances
      measured included buccal, lingual, and centroid transverse widths at the level of
      canines, premolars, and molars as well as arch depth and arch perimeter. RESULTS:
      There was no systematic error associated with the methodology used. Intraclass
      correlation coefficient values were higher than 0.70 on every measure. The
      average random error in the maxilla was 1.5 degrees +/-0.4 degrees  for torque,
      1.8 degrees +/-0.5 degrees  for tip, and 0.4+/-0.2 mm for linear measurements.
      The average random error in the mandible was 1.2 degrees +/-0.3 degrees  for
      torque, 2.0 degrees +/-0.8 degrees  for tip, and 0.1+/-0.1 mm for the linear
      measurements. CONCLUSIONS: A custom digital analysis protocol to measure
      traditional linear measurements as well as tip and torque angulation on virtual
      dental casts was presented. This validation study demonstrated that the digital
      analysis used in this study has adequate reproducibility, providing additional
      information and more accurate intra-arch measurements for clinical diagnosis and
      dentofacial research.

PMID- 24325840
TI  - Dentoalveolar class III treatment using retromolar miniscrew anchorage.
AB  - In this article, we report the successful use of miniscrews in the distalization
      of the lower dentition to correct an Angle class III malocclusion with lower
      anterior crowding in a dolichofacial adult patient. Conventional intraoral and
      extraoral appliances have many disadvantages, including the need for patient
      cooperation, potential for anchorage loss, and vertical extrusion of upper molars
      and lower incisors. Extrusion should be prevented or minimized when treating long
      faced patients with reduced overbite. After third molar extractions, miniscrews
      were placed in the retromolar area. A sliding jig was applied to distalize the
      lower molars, while the anterior teeth were bonded and retracted secondarily to
      avoid round tripping. After 18 months of treatment, molar and canine class I
      relationship with normal overjet and overbite were achieved. In addition, there
      was an esthetic improvement in the profile with only a small increase of the
      lower anterior facial height. These results remained stable at a 12-month follow
      up. 

PMID- 24325841
TI  - Optimizing recruitment to a prostate cancer surveillance program among male BRCA1
      mutation carriers: invitation by mail or by telephone.
AB  - The effectiveness of a genetics-based public health screening programs depend on
      the successful recruitment of subjects who qualify for intensified screening by
      virtue of a positive genetic test. Herein we compare the effectiveness of a
      mailed invitation and follow-up phone call for non-responding subjects and an
      initial invitation by telephone addressed to male BRCA1 mutation carriers for
      prostate screening.The final participation rate was 75% (42 of 56) for men who
      were initially contacted by mail (and follow-up phone call) and 81% (30 of 37)
      for men who were initially contacted by telephone. Among the men who were
      initially contacted by mail, it was necessary to telephone 54% of these patients
      (30 of 56).After a calculation of the cost-effectiveness related to these
      results, we conclude that if the costs of the phone call were to exceed the costs
      of the letter by 2.5 times or more, then savings would be arranged by initiating
      contact with a mailed invitation. 

PMID- 24325842
TI  - Spatial analysis of condyle position according to sagittal skeletal relationship,
      assessed by cone beam computed tomography.
AB  - BACKGROUND: The study aims to compare the condylar position in patients with
      different anteroposterior sagittal skeletal relationships through a cone beam
      computed generated tomography (CBCT) imaging generated space analysis. METHODS:
      This was a retrospective study of clinically justified, previously taken CBCT
      images of 45 subjects. Based on a proper sample calculation, three groups of 15
      CBCT images each were made according to their ANB angle and facial pattern: class
      I (normo facial pattern) and class II and III (long facial pattern). The CBCT
      images were of adult patients between 18 and 35 years old, with full permanent
      dentition at maximum occlusal intercuspidation. Anatomical references previously
      used by Ricketts for the condyle position inside the glenoid fossae were measured
      digitally through the EzImplant software. Analysis of variance, Tukey's, Kruskal
      Wallis, and Mann-Whitney U statistical tests were used. RESULTS: The upper
      distance of the condyle to the glenoid fossa was smaller in the class II and
      class III compared with the class I group. The anterior distance of the condyle
      to the articular eminence showed significant differences when comparing the class
      I with the class II and class III groups. No statistically significant difference
      was noted in the posterior condylar distance between the groups. The angle of the
      eminence showed differences between the three groups, while the eminence height
      showed significant difference when comparing the class I with class III group.
      CONCLUSIONS: Spatial differences existed for the condylar position in relation to
      the glenoid fossa for skeletal class I, class II, and class III, but these
      spatial differences may not be clinically relevant.

PMID- 24325843
TI  - Economic modelling of diagnostic and treatment pathways in National Institute for
      Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways
      in Guidelines (MAPGuide) project.
AB  - BACKGROUND: National Institute for Health and Care Excellence (NICE) clinical
      guidelines (CGs) make recommendations across large, complex care pathways for
      broad groups of patients. They rely on cost-effectiveness evidence from the
      literature and from new analyses for selected high-priority topics. An
      alternative approach would be to build a model of the full care pathway and to
      use this as a platform to evaluate the cost-effectiveness of multiple topics
      across the guideline recommendations. OBJECTIVES: In this project we aimed to
      test the feasibility of building full guideline models for NICE guidelines and to
      assess if, and how, such models can be used as a basis for cost-effectiveness
      analysis (CEA). DATA SOURCES: A 'best evidence' approach was used to inform the
      model parameters. Data were drawn from the guideline documentation, advice from
      clinical experts and rapid literature reviews on selected topics. Where possible
      we relied on good-quality, recent UK systematic reviews and meta-analyses. REVIEW
      METHODS: Two published NICE guidelines were used as case studies: prostate cancer
      and atrial fibrillation (AF). Discrete event simulation (DES) was used to model
      the recommended care pathways and to estimate consequent costs and outcomes. For
      each guideline, researchers not involved in model development collated a
      shortlist of topics suggested for updating. The modelling teams then attempted to
      evaluate options related to these topics. Cost-effectiveness results were
      compared with opinions about the importance of the topics elicited in a survey of
      stakeholders. RESULTS: The modelling teams developed simulations of the guideline
      pathways and disease processes. Development took longer and required more
      analytical time than anticipated. Estimates of cost-effectiveness were produced
      for six of the nine prostate cancer topics considered, and for five of eight AF
      topics. The other topics were not evaluated owing to lack of data or time
      constraints. The modelled results suggested 'economic priorities' for an update
      that differed from priorities expressed in the stakeholder survey. LIMITATIONS:
      We did not conduct systematic reviews to inform the model parameters, and so the
      results might not reflect all current evidence. Data limitations and time
      constraints restricted the number of analyses that we could conduct. We were also
      unable to obtain feedback from guideline stakeholders about the usefulness of the
      models within project time scales. CONCLUSIONS: Discrete event simulation can be
      used to model full guideline pathways for CEA, although this requires a
      substantial investment of clinical and analytic time and expertise. For some
      topics lack of data may limit the potential for modelling. There are also
      uncertainties over the accessibility and adaptability of full guideline models.
      However, full guideline modelling offers the potential to strengthen and extend
      the analytical basis of NICE's CGs. Further work is needed to extend the analysis
      of our case study models to estimate population-level budget and health impacts.
      The practical usefulness of our models to guideline developers and users should
      also be investigated, as should the feasibility and usefulness of whole guideline
      modelling alongside development of a new CG. FUNDING: This project was funded by
      the Medical Research Council and the National Institute for Health Research
      through the Methodology Research Programme [grant number G0901504] and will be
      published in full in Health Technology Assessment; Vol. 17, No. 58. See the NIHR
      Journals Library website for further project information.

PMID- 24325844
TI  - Photostability and toxicity of finasteride, diclofenac and naproxen under
      simulating sunlight exposure: evaluation of the toxicity trend and of the
      packaging photoprotection.
AB  - BACKGROUND: Drugs photostability plays two different opposite roles; a real
      advantage arises considering the longer expiration time of the drugs while the
      consequent persistence in the environment involves an obvious negative effect
      bound to their harmfulness.On this basis we tested the photostability and
      toxicity of three pharmaceutical active principles: Finasteride, Diclofenac and
      Naproxen. The pure active principles, as well as commercial drugs containing
      them, were considered; for the last, the protective effect of the packaging was
      also evaluated. Samples were irradiated according to the ICH Guidelines for
      photostability testing (The International Conference on Harmonisation of
      Technical Requirements for Registration of Pharmaceuticals for Human Use); a
      simulating sunlight source (a mercury-vapor lamp coupled to a tungsten filament
      one) was used to cover the wavelength range 300-2000 nm; Temperature, Relative
      Humidity, Irradiance and Illuminance were maintained constant during the
      photodegradation. The concentrations of the pharmaceutical active principles
      during the photodegradation were monitored by HPLC with UV/Vis detector. Toxicity
      tests were performed by means of an amperometric biosensor based on suspended
      yeast cells. Since the products obtained by the photodegradation process can
      result as toxic or more toxic than the original molecules, tests were performed
      first and after the photodegadation. RESULTS: After 90 hours of exposure the
      concentration resulted lowered by 42.9%, 88.4% and 91% for Finasteride, Naproxen
      and Diclofenac respectively. Toxicity of the pure active principles follows the
      same order of the photostability. After photodegradation a contribute of the
      reaction products was evidenced. CONCLUSIONS: The simple and cheap analytical
      procedure here proposed, allowed to obtain not only data on photostability and
      toxicity of the pure active principles but, even if roughly, also useful
      information on the reactions kinetic and toxicity of the photodegradation
      products.

PMID- 24325845
TI  - Potential of activated carbon to recover randomly-methylated-beta-cyclodextrin
      solution from washing water originating from in situ soil flushing.
AB  - Despite the overall high efficacy of cyclodextrins to accelerate the treatment of
      soil aquifer remediation by in-situ soil flushing, the use in practice remains
      limited because of the high costs of cyclodextrin and high concentrations needed
      to significantly reduce the treatment time. The current study tested the
      potential of activated carbon to treat washing water originating from soil
      flushing in order to selectively separate hydrocarbon contaminants from washing
      water containing cyclodextrin and subsequently reuse the cyclodextrin solution
      for reinfiltration. A high recovery of the cyclodextrin from the washing water
      would reduce the costs and would make the technique economically feasible for
      soil remediation. This study aimed to investigate whether cyclodextrin can pass
      through the activated carbon filter without reducing the cyclodextrin
      concentration when the contaminated washing water is treated and whether the
      presence of cyclodextrin negatively affects the purification potential of
      activated carbon to remove the organic pollutants from the pumped soil water. Lab
      scale column experiments showed that with the appropriate activated carbon 100%
      of cyclodextrin (randomly-methylated-beta-cyclodextrin) can be recovered from the
      washing water and that the effect on the efficiency of activated carbon to remove
      the hydrocarbon contaminants remains limited. These results show that additional
      field tests are useful to make in-situ soil flushing with cyclodextrin both a
      technical and an economical interesting technique. These results might stimulate
      the application of cyclodextrin in soil treatment technology. 

PMID- 24325846
TI  - Distribution of perfluorinated compounds in Lake Taihu (China): impact to human
      health and water standards.
AB  - The distribution in water and sediment, the sources/sinks and the risk of
      perfluorinated compounds (PFCs) in Lake Taihu, China were investigated. The total
      PFCs concentration was 164 to 299 ng L(-1) in water and 5.8 to 35 ng g(-1) (dw)
      in sediment. The highest concentrations of perfluorooctane sulfonate (PFOS) and
      perfluorooctanoate (PFOA) in water were 29.2 ng L(-1) and 136ngL(-1). PFOS was
      largely associated with sediment, whereas short chain PFCs predominated in water.
      The partition coefficient (Kd) was positively correlated with the organic carbon
      fraction (foc) for PFOS but not for the other PFCs. The organic carbon normalized
      partition coefficient (Koc) increased by 0.51 log units for each additional CF2
      moiety from perfluoro-butanesulfonate (PFBS) to PFOS. For the same chain length
      but different functional groups, the log Koc of PFOS was 1.35 units higher than
      PFOA. PFOS exhibited the highest affinity for sediment through the partition
      mechanism, and foc affected the sediment as a sink of PFOS. Although there was no
      immediate health impact by the intake of the water alone, the consumption of
      aquatic products may cause potential health risks for animals/humans on the time
      scale of months to years. The relationship between the concentration, water
      sediment distribution, bioaccumulation and toxicity should be considered in
      determining the water standards of PFCs.

PMID- 24325848
TI  - Differentiation of large (>= 5 cm) gastrointestinal stromal tumors from benign
      subepithelial tumors in the stomach: radiologists' performance using CT.
AB  - PURPOSE: To identify significant CT findings for the differentiation of large (>=
      5 cm) gastric gastrointestinal stromal tumors (GIST) from benign subepithelial
      tumors and to assess whether radiologists' performance in differentiation is
      improved with knowledge of significant CT criteria. MATERIALS AND METHODS: One
      hundred twenty patients with pathologically proven large (>= 5 cm) GISTs (n=99),
      schwannomas (n=16), and leiomyomas (n=5) who underwent CT were enrolled. Two
      radiologists (A and B) retrospectively reviewed their CT images in consensus for
      the location, size, degree and pattern of enhancement, contour, growth pattern
      and the presence of calcification, necrosis, surface ulceration, or enlarged
      lymph nodes. CT findings considered significant for differentiation were
      determined using uni- and multivariate statistical analyses. Thereafter, two
      successive review sessions for the differentiation of GIST from non-GIST were
      independently performed by two other reviewers (C and D) with different expertise
      of 2 and 9 years using a 5-point confidence scale. At the first session,
      reviewers interpreted CT images without knowledge of significant CT findings. At
      the second session, the results of statistical analyses were provided to the
      reviewers. To assess improvement in radiologists' performance, a pairwise
      comparison of receiver operating curves (ROC) was performed. RESULTS:
      Heterogeneous enhancement, presence of necrosis, absence of lymph nodes, and mean
      size of >= 6 cm were found to be significant for differentiating GIST from
      schwannoma (P<0.05). Non-cardial location, heterogeneous enhancement, and
      presence of necrosis were differential CT features of GIST from leiomyoma
      (P<0.05). Multivariate analyses indicated that absence of enlarged LNs was the
      only statistically significant variable for GIST differentiating from schwannoma.
      The area under the curve of both reviewers obtained using ROC significantly
      increased from 0.682 and 0.613 to 0.903 and 0.904, respectively, with information
      of the significant CT findings differentiating GISTs from non-GISTs (P<0.001).
      CONCLUSION: Non-cardial location, heterogeneous enhancement, presence of
      necrosis, larger lesion size, and absence of lymphadenopathy are highly
      suggestive CT findings for large GISTs in differentiation from schwannomas or
      leiomyomas. Regardless of radiologists' expertise, diagnostic performance in
      differentiation can be significantly improved with knowledge of these CT
      findings.

PMID- 24325847
TI  - Frictional resistance exerted by different lingual and labial brackets: an in
      vitro study.
AB  - BACKGROUND: Although much has been written on the implications of friction
      generated between orthodontic archwires and labial brackets, information on
      lingual brackets is still limited. Hence, we set out to investigate the
      frictional resistance exerted by different lingual and labial brackets, including
      both conventional and self-ligating designs. The effect of various factors,
      namely bracket/base width, slot size, inter-bracket distance, and first-
      (ThetacI) and second-order (ThetacII) critical contact angles were evaluated and
      compared. METHODS: A plaster model of a pretreatment oral cavity was replicated
      to provide 18 (9 upper and 9 lower) identical versions. The anterior segments of
      each were taken, and the canine and lateral and central incisors were mounted
      with either lingual (7th Generation, STb, New STb, In-Ovation L, ORJ) or labial
      (Mini-Mono, Mini Diamond, G&H Ceramic) brackets. Mechanical friction tests were
      performed on each type of bracket using a universal testing machine. The maximum
      force necessary to displace NiTi wires of two different diameters (0.012, 0.014)
      was measured, using both elastic and metal ligatures with conventional brackets.
      RESULTS: The frictional force necessary to displace the wires increased as the
      diameter of the wire increased in all tested brackets (p<0.01). Friction was
      significantly higher (p<0.001) with elastic ligatures, as compared with metal
      ones, in all conventional brackets. In the lower lingual group, significantly
      lower friction was generated at conventional lingual New STb brackets (p<0.01)
      and ORJ lingual brackets (p<0.05) than at self-ligating In-Ovation L lingual
      brackets. A significant statistical correlation between (ThetacI) and friction
      was detected in the lower labial bracket group. CONCLUSIONS: Friction resistance
      is influenced not only by the bracket type, type of ligation, and wire diameter
      but also by geometric differences in the brackets themselves.

PMID- 24325849
TI  - How temporal frequency affects global form coherence in Glass patterns.
AB  - Glass patterns are textural moires from random dots. Sequential presentation of
      Glass patterns induces a sense of illusory motion. We evaluated how changes in
      temporal frequency affected the detection of global form in Glass patterns. We
      found linear improvement in coherence thresholds with increasing temporal
      frequency (Experiment 1), particularly in stimuli with large dot-pair separations
      (Experiment 2). These results support the notion that temporal and orientation
      information sum to boost sensitivity to visually obscure objects, and are
      discussed within the framework of "motion streak" detectors. 

PMID- 24325850
TI  - Perceptual learning as a possible new approach for remediation and prevention of
      developmental dyslexia.
AB  - Learning to read is extremely difficult for about 10% of children across cultures
      because they are affected by developmental dyslexia (DD). According to the
      dominant view, DD is considered an auditory-phonological processing deficit.
      However, accumulating evidence from developmental and clinical vision science,
      suggests that the basic cross-modal letter-to-speech sound integration deficit in
      DD might arise from a mild atypical development of the magnocellular-dorsal
      pathway which also contains the main fronto-parietal attentional network. Letters
      have to be precisely selected from irrelevant and cluttering letters by rapid
      orienting of visual attention before the correct letter-to-speech sound
      integration applies. Our aim is to review the literature supporting a possible
      role of perceptual learning (PL) in helping to solve the puzzle called DD. PL is
      defined as improvement of perceptual skills with practice. Based on the previous
      literature showing how PL is able to selectively change visual abilities, we here
      propose to use PL to improve the impaired visual functions characterizing DD and,
      in particular, the visual deficits that could be developmentally related to an
      early magnocellular-dorsal pathway and selective attention dysfunction. The
      crucial visual attention deficits that are causally linked to DD could be,
      indeed, strongly reduced by training the magnocellular-dorsal pathway with the
      PL, and learning to read for children with DD would not be anymore such a
      difficult task. This new remediation approach - not involving any phonological or
      orthographic training - could be also used to develop new prevention programs for
      pre-reading children at DD risk. 

PMID- 24325851
TI  - The effect of feedback on performance and brain activation during perceptual
      learning.
AB  - We investigated the role of informative feedback on the neural correlates of
      perceptual learning in a coherent-motion detection paradigm. Stimulus displays
      consisted of four patches of moving dots briefly (500 ms) presented
      simultaneously, one patch in each visual quadrant. The coherence level was varied
      in the target patch from near threshold to high, while the other three patches
      contained only noise. The participants judged whether coherent motion was present
      or absent in the target patch. To guarantee central fixation, a secondary RSVP
      digit-detection task was performed at fixation. Over six training sessions
      subjects learned to detect coherent motion in a predefined quadrant (i.e., the
      learned location). Half of our subjects were randomly assigned to the feedback
      group, where they received informative feedback after each response during
      training, whereas the other group received non-informative feedback during
      training that a response button was pressed. We investigated whether the presence
      of informative feedback during training had an influence on the learning success
      and on the resulting BOLD response. Behavioral data of 24 subjects showed
      improved performance with increasing practice. Informative feedback promoted
      learning for motion displays with high coherence levels, whereas it had little
      effect on learning for displays with near-threshold coherence levels. Learning
      enhanced fMRI responses in early visual cortex and motion-sensitive area MT+ and
      these changes were most pronounced for high coherence levels. Activation in the
      insular and cingulate cortex was mainly influenced by coherence level and trained
      location. We conclude that feedback modulates behavioral performance and, to a
      lesser extent, brain activation in areas responsible for monitoring perceptual
      learning.

PMID- 24325852
TI  - Pharmacophore mapping-based virtual screening followed by molecular docking
      studies in search of potential acetylcholinesterase inhibitors as anti
      Alzheimer's agents.
AB  - Alzheimer's disease (AD) is turning out to be one of the lethal diseases in older
      people. Acetylcholinesterase (AChE) is a crucial target in designing of drugs
      against AD. The present in silico study was carried out to explore natural
      compounds as potential AChE inhibitors. Virtual screening, via drug-like ADMET
      filter, best pharmacophore model and molecular docking analyses, has been
      utilized to identify putative novel AChE inhibitors. The InterBioScreen's Natural
      Compound (NC) database was first filtered by applying drug-like ADMET properties
      and then with the pharmacophore-based virtual screening followed by molecular
      docking analyses. Based on docking score, interaction patterns and calculated
      activity, the final hits were selected and these consist of coumarin and non
      coumarin classes of compounds. Few hits were found to have been already reported
      for their AChE inhibitory activity in different literatures confirming
      reliability of our pharmacophore model. The remaining hits are suggested to be
      potential AChE inhibitors for AD. 

PMID- 24325853
TI  - The diagnostic performance of dental maturity for identification of the
      circumpubertal growth phases: a meta-analysis.
AB  - The present meta-analysis initially evaluates the reliability of dental
      maturation in the identification of the circumpubertal growth phases, essentially
      for determining treatment timing in orthodontics. A literature survey was
      performed using the Medline, LILACS and SciELO databases, and the Cochrane
      Library (2000 to 2011). Studies of the correlation between dental and cervical
      vertebral maturation methods were considered. The mandibular canine, the first
      and second premolars, and the second molar were investigated. After the
      selection, six articles qualified for the final analysis. The overall correlation
      coefficients were all significant, ranging from 0.57 to 0.73. Five of these
      studies suggested the use of dental maturation as an indicator of the growth
      phase. However, the diagnostic performance analysis uncovered limited reliability
      only for the identification of the pre-pubertal growth phase. The determination
      of dental maturity for the assessment of treatment timing in orthodontics is not
      recommended. 

PMID- 24325854
TI  - Morphology and evolution of Myriapoda.

PMID- 24325855
TI  - Loving memories of Dr. Ko Shimamoto.

PMID- 24325857
TI  - Hypolipidemic effect of the polysaccharides extracted from pumpkin by cellulase
      assisted method on mice.
AB  - The fruit of pumpkin (Cucurbita moschata) is one of the most important vegetables
      in the world. This study was conducted to investigate the hypolipidemic effect of
      the polysaccharide isolated from pumpkin (PP). Male Sprague-Dawley rats were
      divided into three groups and treated with diets containing either high fat, PP,
      or normal fat. Oral administration of PP could significantly decrease the levels
      of plasma triacylglycerol (TG), total cholesterol (TC), and plasma low-density
      lipoprotein cholesterol and increase the levels of fecal fat, cholesterol, and
      plasma high-density lipoprotein cholesterol. Therefore, results suggest that PP
      had a high hypolipidemic activity and could be explored as a possible agent for
      hyperlipidemia. 

PMID- 24325856
TI  - Studies on the rheological and gelatinization characteristics of waxy wheat
      flour.
AB  - The chemical composition, rheological and gelatinization characteristics of waxy
      wheat flour were investigated. Compared with wheat flour, waxy wheat flour has
      lower protein (9.52%), amylase (1.02%) and higher crude starch (73.19%) contents.
      Because of its different chemical composition, waxy wheat flour exhibited some
      better processing characteristics (water-holding capacity, dough development
      time, extensibility, swelling power and setback) than normal wheat flour. It also
      exhibited some defects in rheological characteristics, including a higher degree
      of softening, a lower Farinograph quality number and smaller resistance to
      extensibility ratio. Differential scanning calorimetry results showed that waxy
      wheat flour gelatinized at higher onset (To=60.9  degrees C), peak (Tp=64.9 
      degrees C), conclusion (Tc=73.6  degrees C) temperatures and required more energy
      (DeltaH=7.6J/g) to melt gelatinized starch gels. The results of this
      investigation indicated that blending waxy wheat flour with normal flour is a
      promising way to improve product quality in baked foods and to prolong the shelf
      life of these products.

PMID- 24325858
TI  - N-O, carboxymethyl chitosan enhanced scaffold porosity and biocompatibility under
      e-beam irradiation at 50 kGy.
AB  - In this study, a chitosan co-polymer scaffold was prepared by mixing poly(vinyl
      alcohol) (PVA), NO, carboxymethyl chitosan (NOCC) and polyethylene glycol (PEG)
      solutions to obtain desirable properties for chondrocyte cultivation. Electron
      beam (e-beam) radiation was used to physically cross-link these polymers at
      different doses (30 kGy and 50 kGy). The co-polymers were then lyophilized to
      form macroporous three-dimensional (3-D) matrix. Scaffold morphology, porosity,
      swelling properties, biocompatibility, expression of glycosaminoglycan (GAG) and
      type II collagen following the seeding of primary chondrocytes were studied up to
      28 days. The results demonstrate that irradiation of e-beam at 50 kGy increased
      scaffold porosity and pore sizes subsequently enhanced cell attachment and
      proliferation. Scanning electron microscopy and transmission electron microscopy
      revealed extensive interconnected microstructure of PVA-PEG-NOCC, demonstrated
      cellular activities on the scaffolds and their ability to maintain chondrocyte
      phenotype. In addition, the produced PVA-PEG-NOCC scaffolds showed superior
      swelling properties, and increased GAG and type II collagen secreted by the
      seeded chondrocytes. In conclusion, the results suggest that by adding NOCC and
      irradiation cross-linking at 50 kGy, the physical and biological properties of
      PVA-PEG blend can be further enhanced thereby making PVA-PEG-NOCC a potential
      scaffold for chondrocytes.

PMID- 24325859
TI  - Preparation and characterization of chitosan-zirconium(IV) composite for
      adsorption of vanadium(V).
AB  - In this present study, an inorganic-biopolymer composite based on chitosan
      zirconium(IV) was prepared and investigated as a biosorbent for the removal of
      vanadium(V) ions from aqueous solution. The resulting composite before and after
      adsorbed V(V) were characterized by using FT-IR, XRD, SEM and EDS, respectively.
      Various relevant parameters affecting the adsorption capacity such as pH, initial
      concentration, contact time, temperature and co-existing ions were evaluated. The
      results demonstrated that the optimum pH was found to be 4.0 and the equilibrium
      was achieved after 4h for V(V) adsorption. The Langmuir isotherm model could be
      well described the adsorption of V(V), with the maximum adsorption capacity of
      208 mg g(-1) at 30  degrees C. The kinetics data were well fitted to pseudo
      second-order equation, indicating that chemical sorption as the rate-limiting
      step of adsorption mechanism. The calculated thermodynamic parameters such as
      DeltaG degrees , DeltaH degrees  and DeltaS degrees  indicated that the
      adsorption process was feasible, spontaneous and endothermic in nature. Moreover,
      co-existing ions including nitrate, chloride and sulfate had a certain effect on
      the uptake of V(V). The V(V) loaded chitosan-zirconium(IV) composite could be
      regenerated by 0.01 mol L(-1) sodium hydroxide, with efficiency greater than 95%.

PMID- 24325860
TI  - Inhibitory effects of beta-ionone on amyloid fibril formation of beta
      lactoglobulin.
AB  - beta-Lactoglobulin (beta-LG) is the major constituent of whey food, which has
      been shown to interact with a wide range of aroma compounds. In the present work,
      a model aroma compound, beta-ionone, is used to investigate the influence of
      aroma compounds on the urea-induced unfolding of beta-LG at pH 7.0. beta-Ionone
      is observed to enhance the stability of beta-LG at pH 7.0. Moreover, the amyloid
      fibrils are observed when beta-LG at pH 7.0 is incubated for 12-20 days at 37 
      degrees C in the presence of 3-5M urea. However, the formation of amyloid fibrils
      is inhibited when beta-ionone is added into the samples and the inhibitory
      effects follow a concentration-dependent fashion. There is a clear correlation
      between Cm and lag time. The correlation demonstrates that protein stability
      affects the amyloid fibril formation of beta-LG. The results highlight the
      critical role of protein stability and provide an approach to prevent the
      formation of amyloid fibrils in vitro.

PMID- 24325861
TI  - Structural features and biological activities of the polysaccharides from
      Astragalus membranaceus.
AB  - Recently, a great deal of interest has been developed to isolate and investigate
      novel bioactive components with health benefit effects from natural resources.
      The dried root of Astragalus membranaceus, one of the most popular health
      promoting herbal medicines, has been used historically as an immunomodulating
      agent for the treatment of common cold, diarrhea, fatigue and anorexia for more
      than 2000 years. Modern phytochemistry and pharmacological experiments have
      proved that polysaccharide is one of the major active ingredients in the root of
      A. membranaceus with various important bioactivities, such as immunomodulation,
      antioxidant, antitumor, anti-diabetes, antiviral, hepatoprotection, anti
      inflammation, anti-atherosclerosis, hematopoiesis and neuroprotection. The aim of
      the present review is to summarize previous and current references and give a
      comprehensive summary regarding the structural features and biological activities
      of A. membranaceus polysaccharides in order to provide new insight for further
      development of these macromolecules. 

PMID- 24325863
TI  - The effect of different surface treatments of demineralised enamel on
      microleakage under metal orthodontic brackets.
AB  - BACKGROUND: The aim of this investigation was to assess the effects of different
      treatments of demineralised enamel on microleakage under orthodontic brackets.
      METHODS: Seventy-five intact premolars were randomly assigned to five groups. The
      teeth in groups 2 through 5 were immersed in a demineralising solution for 16
      weeks. In groups 1 (control) and 2 (demineralised/control), conventional acid
      etching was used. In group 3, sodium hypochlorite (NaOCl) was applied on the
      enamel surface for 1 min after acid etching, and in group 4, Transbond Plus (3M
      Unitek, Monrovia, CA, USA) self-etching primer (SEP) was used. The teeth in group
      5 were treated with 2% sodium fluoride (NaF) for 4 min before etching. After
      bracket bonding, the specimens were thermocycled, sealed with nail varnish,
      immersed in 0.5% basic fuchsine solution for 24 h and sectioned. Microleakage was
      measured under a stereomicroscope for the enamel-adhesive and adhesive-bracket
      interfaces of both occlusal and gingival sides. RESULTS: Demineralised teeth
      showed more microleakage at the enamel-adhesive interface on both occlusal and
      gingival sides compared to sound teeth, but the difference was not significant
      (P>0.005). Treating the demineralised enamel with 5% NaOCl or Transbond Plus SEP
      was not effective in reducing microleakage. NaF treatment followed by acid
      etching of demineralised enamel resulted in significantly lower microleakage in
      most comparisons (P<0.005). CONCLUSIONS: The use of 2% NaF on hypomineralised
      enamel before the bracket bonding procedure is an effective way to decrease
      microleakage.

PMID- 24325864
TI  - Population prevalence and control of cardiovascular risk factors: what electronic
      medical records tell us.
AB  - OBJECTIVE: To analyze the prevalence, control, and management of hypertension,
      hypercholesterolemia, and diabetes mellitus type 2 (DM2). DESIGN: Cross-sectional
      analysis of all individuals attended in the Catalan primary care centers between
      2006 and 2009. LOCATION: History of cardiovascular diseases, diagnosis and
      treatment of hypertension, hypercholesterolemia, DM2, lipid profile, glycemia and
      blood pressure data were extracted from electronic medical records. Age
      standardized prevalence and levels of management and control were estimated.
      PARTICIPANTS: Individuals aged 35-74 years using primary care databases. MAIN
      MEASURES: A total of 2,174,515 individuals were included (mean age 52 years [SD
      11], 47% men). RESULTS: Hypertension was the most prevalent cardiovascular risk
      factor (39% in women, 41% in men) followed by hypercholesterolemia (38% and 40%)
      and DM2 (12% and 16%), respectively. Diuretics and angiotensin-converting enzyme
      inhibitors were most often prescribed for hypertension control (<140/90mmHg,
      achieved in 68% of men and 60% of women treated). Hypercholesterolemia was
      controlled (low-density lipoprotein cholesterol <130mg/dl) in just 31% of men and
      26% of women with no history of cardiovascular disease, despite lipid-lowering
      treatment, primarily (90%) with statins. The percentage of women and men with DM2
      and with glycated hemoglobin <7% was 64.7% and 59.2%, respectively; treatment was
      predominantly with oral hypoglycemic agents alone (70%), or combined with insulin
      (15%). CONCLUSIONS: Hypertension was the most prevalent cardiovascular risk
      factor in the Catalan population attended at primary care centers. About two
      thirds of individuals with hypertension or DM2 were adequately controlled;
      hypercholesterolemia control was particularly low.

PMID- 24325865
TI  - Renal cell carcinoma metastasis to thyroid tumor: a case report and review of the
      literature.
AB  - INTRODUCTION: Metastatic neoplasms to the thyroid gland are rare in clinical
      practice. Clear cell renal carcinoma is the most frequent site of origin of
      thyroid metastases and represents 12 to 34% of all secondary thyroid tumors.
      Tumor-to-tumor metastases, in which a thyroid neoplasm is the recipient of a
      metastasis, are exceedingly rare. We report a case of clear cell renal carcinoma
      metastatic to a follicular adenoma. This is the tenth case of renal cell
      carcinoma metastasis to thyroid tumor reported in the literature. CASE
      PRESENTATION: A 62-year-old Caucasian woman with a history of clear cell renal
      carcinoma was admitted to our institution for multinodular goiter. A histological
      examination after total thyroidectomy revealed clear cell renal carcinoma
      metastasis to a thyroid follicular adenoma. CONCLUSIONS: Preoperative diagnosis
      of secondary thyroid neoplasm is difficult to achieve. The diagnosis of
      metastatic disease should be taken into account if patients have a history of
      clear cell renal carcinoma or if there is a multifocal growth pattern and clear
      cell appearance of the cytoplasm.

PMID- 24325866
TI  - The two major isoforms of thyroid hormone receptor, TRalpha1 and TRbeta1,
      preferentially partner with distinct panels of auxiliary proteins.
AB  - Thyroid hormone receptors (TRs) are expressed primarily as two major isoforms,
      TRalpha1 and TRbeta1, which are expressed at different times in development and
      at different tissue abundances in the adult. The transcription properties and
      biological properties of TRalpha1 and TRbeta1 can differ. We report here that
      although overlapping, TRalpha1 and TRbeta1 recruit distinct panels of partner
      proteins that may account for their divergent biological functions, and which
      appear to explain their distinct target gene regulatory properties. 

PMID- 24325867
TI  - Development of monoclonal antibodies against human CYP11B1 and CYP11B2.
AB  - 1. The final enzymes in the biosynthesis of aldosterone and cortisol are by the
      cytochrome P450 CYP11B2 and CYP11B1, respectively. The enzymes are 93% homologous
      at the amino acid level and specific antibodies have been difficult to generate.
      2. Mice and rats were immunized with multiple peptides conjugated to various
      immunogenic proteins and monoclonal antibodies were generated. The only peptide
      sequences that generated specific antibodies were amino acids 41-52 for the
      CYP11B2 and amino acids 80-90 for the CYP11B1 enzyme. 3. The mouse monoclonal
      CYP11B2-41 was specific and sensitive for use in western blots and produced
      specific staining of the zona glomerulosa of normal adrenal glands. The rat
      monoclonal CYP11B1-80 also detected a single band by western blot and detected
      only the zona fasciculata. Triple immunofluorescence of the adrenal demonstrated
      that the CYP11B1 and the CYP11B2 did not co-localize, while as expected the
      CYP11B1 co-localized with the 17alpha-hydroxylase.

PMID- 24325868
TI  - HOXB13 contributes to G1/S and G2/M checkpoint controls in prostate.
AB  - HOXB13 is a homeobox protein that is expressed in normal adult prostate and colon
      tissues; however, its deregulated expression was evidenced in various
      malignancies. To characterize the putative role of HOXB13 in cell cycle
      progression, we performed overexpression and siRNA-mediated knockdown studies in
      PC-3 and LNCaP cells. Immunohistochemistry (IHC) analyses were also performed
      using formalin-fixed, paraffin-embedded tissues containing normal, H-PIN and PCa
      sections from 20 radical prostatectomy specimens. Furthermore, when the role of
      HOXB13 during cell cycle progression, association with cyclins, cell growth and
      colony formation using real-time cell proliferation were assessed, we observed
      that ectopic expression of HOXB13 accumulated cells at G1 through decreasing the
      cyclin D1 level by promoting its ubiquitination and degradation. This loss slowed
      S phase entry in both cell lines examined, with an associated decrease in
      pRb((S780) and (S795)) phosphorylations. Contrary, siRNA-mediated depletion of
      HOXB13 expression noticeably increased cyclin levels, stabilized E2F1 and CDC25C,
      subsequent to increased pRb phosphorylations. This increase in Cyclin B1 and
      CDC25C both together facilitated activation of cyclin B complex via
      dephosphorylating CDK1((T14Y15)), and resumed the G2/M transition after
      nocodazole synchronization. Despite an increase in the total expression level and
      cytoplasmic retention of HOXB13 in H-PIN and PCa samples that were observed via
      IHC evaluation of prostate tissues, HOXB13 depletion facilitated to an increase
      in PC-3 and LNCaP cell proliferation. Thus, we suggest that HOXB13 expression is
      required for cell cycle regulation, and increases by an unknown mechanism
      consequent to its functional loss in cancer. 

PMID- 24325869
TI  - YY1 represses the transcriptional activity of Runx2 in C2C12 cells.
AB  - Runx2 is a major transcription factor that induces osteoblast differentiation by
      bone morphogenetic proteins (BMPs). Conversely, YY1 is a transcription factor
      that inhibits BMP2-induced cell differentiation. Until now, there has been no
      understanding of how osteoblast differentiation by Runx2 and YY1 is regulated. In
      this study we focused on the relationship between Runx2 and YY1. We confirmed
      that alkaline phosphatase staining is repressed by YY1. Runx2 interacted with YY1
      through Runt and the C-terminus domain of Runx2. YY1 markedly repressed the Runx2
      mediated enhancement of transcriptional activity on the osteocalcin and alkaline
      phosphatase promoters. Knockdown of YY1 enhanced BMP2- and Runx2-induced
      osteoblast differentiation. YY1 decreased Runx2 DNA binding affinity. The results
      indicate that YY1 represses osteoblast differentiation by an interaction with
      Runx2 and inhibits the transcriptional activity of Runx2. 

PMID- 24325870
TI  - Development of an in vitro assay based on humoral immunity for quality control of
      oil-adjuvant Pseudotuberculosis vaccine in Yellowtail Seriola quinqueradiata.
AB  - Photobacterium damselae subsp. piscicida is an infectious pathogen that causes
      Pseudotuberculosis in Yellowtail fish. In Japan, several oil-adjuvant vaccines
      for Pseudotuberculosis have been approved for control of infectious diseases in
      aquaculture. Before distribution of an approved fish vaccine, an artificial
      challenge test for quality control is performed by the manufacturer and National
      Veterinary Assay Laboratory under Pharmaceutical Law of Japan to confirm potency.
      In this study, artificial challenge tests with a range of five diluted or
      undiluted approved vaccines was performed to determine the relationship between
      antigen levels and vaccine efficacy. Immunization of fish with the undiluted
      vaccine prevented Pseudotuberculosis. Results of artificial challenge tests
      demonstrated vaccine efficiency was dose dependent. Agglutination assays using
      immune sera were performed to determine agglutination titers, which were also
      dose dependent. These results suggest a link between survival rate in the
      artificial challenge tests and agglutination titers. Western blotting analysis
      identified a specific protein approximately 37 kDa in size in vaccinated fish. We
      confirmed antibodies were produced in vaccinated fish by immunoreactions with the
      approved vaccine. An agglutination assay based on humoral immunoreactions would
      be a useful alternative to the artificial challenge test for quality control of
      vaccines for aquaculture. 

PMID- 24325871
TI  - Anti-A and anti-B haemagglutinin levels in intravenous immunoglobulins: are they
      on the rise? A comparison of four different analysis methods and six products.
AB  - Recent reports of severe haemolytic reactions upon high dose treatment with new
      generation intravenous immunoglobulins (IVIGs) prompted us to examine the anti-A
      and anti-B haemagglutinin content of these therapeutics. We compared four
      different test methods, namely the indirect and direct haemagglutination test as
      described in the European Pharmacopoiea (Ph. Eur.) and two commercial gelcard
      systems with the aim to define the most reliable method for a large-scale
      comparison of different IVIG products. Absolute titres varied when the same
      samples were analyzed by the four methods, while the relative ranking of six
      different IVIG preparations representing different manufacturing classes was
      identical. New generation IVIGs showed 1-2 titre steps higher anti-A titres than
      the older products. Haemagglutinin titres of all 48 IVIG batches analyzed were
      within the current Ph. Eur. specification of <=1:64 when tested by the official
      pharmacopoeial method. Based on efficiency, reliability and lower costs, the
      direct gelcard method could be a valid alternative to the official Ph. Eur.
      method to serve as a limit test. However, due to the highest intermediate
      precision, the official Ph. Eur. method seems to be most suitable to compare
      haemagglutinin titres of different IVIG products. 

PMID- 24325872
TI  - Molecular characteristics of MDR Mycobacterium tuberculosis strains isolated in
      Fujian, China.
AB  - Of 75 MDR isolates from Fujian Province, the sensitivity of RIF, INH, EMB, SM,
      OFLX and KAN resistance by DNA sequencing was 96.0%, 96.0%, 66.7%, 66.0%, 84.2%
      and 75.0%, respectively. We also identified that minority mutations in the mixed
      Mycobacterium tuberculosis population may be responsible for two "false-negative"
      results. In addition, Beijing genotype is still the predominant sublineage in the
      MDR TB cases from Fujian. 

PMID- 24325873
TI  - Expression and immunolocalisation of TpFABP as a candidate antigen for the
      serodiagnosis of rabbit Taenia pisiformis cysticercosis.
AB  - The larval stage of Taenia pisiformis, also known as Cysticercus pisiformis, is
      the causative agent of cysticercosis and the cause of severe health problems in
      rabbits that negatively impacts on husbandry production. To date, there is no
      fast detection method to identify early infections in rabbits. In the present
      study, a new dot-ELISA-based on an endogenous antigen fatty acid-binding protein
      (FABP) was developed for the detection of cysticercosis, and its potential was
      then evaluated using test serum samples. Immunolocalisation showed that T.
      pisiformis FABP (TpFABP) localised to the parenchyma of the bladder wall of the
      cysticercus and perinuclear cytoplasm of parenchyma of the adult parasite. After
      cloning and expression, recombinant TpFABP (rTpFABP) protein was used for
      serodiagnosis of T. pisiformis infection in rabbits by dot-ELISA. The antibody
      was detected 14 days post-infection in rabbits experimentally infected with T.
      pisiformis. Based on the necropsy results, the sensitivity and specificity of 169
      serum samples tested by rTpFABP dot-ELISA were found to be 98.2% (54/55) and
      92.1% (105/114), respectively. These data suggest that the dot-ELISA developed in
      this study has potential for detection of T. pisiformis infection in rabbits. 

PMID- 24325874
TI  - Treatment decision-making in the medical encounter: comparing the attitudes of
      French surgeons and their patients in breast cancer care.
AB  - OBJECTIVES: To explore attitudes of French surgeons and their patients towards
      treatment decision-making (TDM) in the medical encounter. METHODS: Surgeons
      involved in early stage breast cancer and their patients treated in a French
      cancer care network received a cross-sectional survey questionnaire containing
      examples of four different approaches to TDM: paternalistic, "some sharing",
      informed TDM and, shared TDM. RESULTS: Surgeons' interaction styles were clearly
      distributed among paternalistic, shared and mixed. The paternalistic approach
      seemed to be associated with private rather than public practice and with less
      professional experience. Patients reported a rather low level of participation in
      TDM, varying by socio-demographic characteristics. One third of patients were
      dissatisfied with the way their treatment decision had been made. CONCLUSION:
      Most surgeons reported adopting the "some sharing" approach. However, one patient
      out of three reported that they would have liked to participate more in the TDM
      process. PRACTICE IMPLICATIONS: Surgeons need to ask patients what their
      preferences for involvement in TDM are and then think about ways to accommodate
      both their own and patients' preferences regarding the TDM process to be used in
      each encounter. In addition, decision aids could be offered to surgeons to help
      them discuss treatment options with their patients.

PMID- 24325875
TI  - Nutritional behavior and attitudes in food allergic children and their mothers.
AB  - BACKGROUND: Avoidance of food allergens requires adapting dietetic habits,
      changing nutritional approach. A restriction of food choice can result in a
      monotonous diet and impact social life. This study investigated the impact of
      food allergy on nutritional behavior and attitudes of patients and their
      families. METHODS: A survey involving mothers of food allergic children aged 0-16
      years was carried out. We primarily studied the variables related to the child
      (age, gender, clinical history, food and social events attitudes). In addition,
      Spielberg Trait-Anxiety Inventory (STAI-T) test was applied to the mothers. We
      assessed separately the associations between characteristics of child-mother
      pairs and diet monotony, and attendance to social events, by means of
      proportional odds regression models. RESULTS: Nearly 10% of the 124 participants
      completely banned allergenic foods at home and 15.3% consumed their meals
      separately. More than one fourth attended parties rarely or never. Most of the
      participants reported a "monotonous diet". Model results suggested significant
      associations between child age (p = 0.05), mother age (p = 0.05), number of
      excluded foods (p = 0.003) and monotony of the diet. The attendance of social
      events was inversely associated with the number of excluded foods (p = 0.04) and
      the mother's STAI-T T-score (p = 0.04). CONCLUSIONS: The results highlighted the
      impact of food allergy in reducing interest about food and influencing patients'
      approach to social life. It is important to support families in managing
      allergens avoidance.

PMID- 24325876
TI  - Development of a new laboratory test to evaluate antithrombin resistance in
      plasma.
AB  - INTRODUCTION: We recently reported a variant prothrombin (p.Arg596Leu:
      prothrombin Yukuhashi) that confers antithrombin resistance to patients with
      hereditary thrombosis. To detect antithrombin resistance in plasma, we devised a
      laboratory test analyzing the kinetics of thrombin inactivation using
      antithrombin. MATERIALS AND METHODS: After incubation with prothrombin activator
      components (phospholipids, CaCl2, and snake venom), samples were treated with
      excess antithrombin in the presence or absence of heparin for various time
      periods. Subsequently, H-D-Phe-Pip-Arg-p-nitoranilide was added and changes in
      absorbance/min (DeltaA/min) were measured at 405 nm. RESULTS: After 1 min
      inactivation using antithrombin and heparin, the relative residual thrombin
      activity of recombinant mutant prothrombin (34.3% +/- 2.2%) was higher than that
      of the wild-type (6.3% +/- 1.2 %). After 30 min without heparin, the relative
      residual thrombin activity of recombinant mutant prothrombin (95.8% +/- 0.4%) was
      higher than that of the wild-type (10.1% +/- 1.7%), indicating that this assay
      could detect antithrombin resistance of the variant 596Leu prothrombin. Moreover,
      warfarinized plasmas from 2 heterozygous patients with prothrombin Yukuhashi
      mutation clearly showed higher values of the relative residual thrombin activity
      than those from 5 thrombosis patients lacking the mutation in the presence or
      absence of heparin. CONCLUSIONS: We have devised a laboratory test to detect
      antithrombin resistance in plasma by analyzing the kinetics of thrombin
      inactivation using antithrombin. This assay may be useful for detecting
      antithrombin resistance in plasma, even in warfarinized patients.

PMID- 24325877
TI  - Elevated plasma levels of soluble platelet glycoprotein VI (GPVI) in patients
      with thrombotic microangiopathy.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) is caused by various conditions,
      such as decreased a ADAMTS13 level, activated or injured vascular endothelial
      cells or activated platelets. This study examined the soluble platelet
      glycoprotein VI (sGPVI) levels in patients with TMA to evaluate the activation of
      platelets in thrombotic states. MATERIALS AND METHODS: The plasma levels of
      sGPVI, ADAMTS13 activity, von Willebrand factor (VWF) and VWF propeptide (VWFpp)
      were measured in patients with TMA. RESULTS: The plasma levels of sGPVI were
      significantly higher in postoperative patients, patients with TMA and those with
      disseminated intravascular coagulation (DIC) than in those without thrombosis.
      The plasma levels of sGPVI were the highest in patients with TMA without markedly
      reduced ADAMTS13 and those were significantly reduced after plasma exchange.
      CONCLUSION: The measurement of sGPVI level is therefore considered to be
      important for the diagnosis and evaluation of TMA.

PMID- 24325878
TI  - Lentiviral vector platform for improved erythropoietin expression concomitant
      with shRNA mediated host cell elastase down regulation.
AB  - Lentiviral vector (LV) mediated gene transfer holds great promise to develop
      stable cell lines for sustained transgene expression providing a valuable
      alternative to the conventional plasmid transfection based recombinant protein
      production methods. We report here making a third generation HIV-2 derived LV
      containing erythropoietin (EPO) gene expression cassette to generate a stable
      HEK293 cell line secreting EPO constitutively. A high producer cell clone was
      obtained by limiting dilution and was adapted to serum free medium. The
      suspension adapted cell clone stably produced milligram per liter quantities of
      EPO. Subsequent host metabolic engineering using lentiviral RNAi targeted to
      block an endogenous candidate protease elastase, identified through an in silico
      approach, resulted in appreciable augmentation of EPO expression above the
      original level. This study of LV based improved glycoprotein expression with host
      cell metabolic engineering for stable production of protein therapeutics thus
      exemplifies the versatility of LV and is of significant future biopharmaceutical
      importance. 

PMID- 24325879
TI  - Imaging in thoracic oncology: case studies from Multidisciplinary Thoracic Tumor
      Board: (part 2 of 2 part series).
AB  - Multidisciplinary tumor board conferences foster collaboration among health care
      providers from a variety of specialties and help to facilitate optimal patient
      care. Generally, the clinical questions revolve around the best options for
      establishing a diagnosis, staging the disease and directing treatment. This
      article describes and illustrates the clinical scenarios of three patients who
      were presented at our thoracic Tumor Board, focusing on management issues and the
      role of imaging. These patients had invasive thymoma; concurrent small cell lung
      cancer and non-small cell lung cancer; and esophageal cancer with celiac lymph
      node metastases, respectively. 

PMID- 24325880
TI  - Comparative outcomes and cost-utility after surgical treatment of focal lumbar
      spinal stenosis compared with osteoarthritis of the hip or knee--part 1: long
      term change in health-related quality of life.
AB  - BACKGROUND CONTEXT: It is well accepted that total hip and knee arthroplasty
      (THA/TKA) for osteoarthritis (OA) is associated with reliable and sustained
      improvements in postoperative health-related quality of life (HRQoL). Although
      several studies have demonstrated comparable outcomes with THA/TKA after surgical
      intervention for lumbar spinal stenosis (LSS), the sustainability of the outcome
      after LSS surgery compared with THA/TKA remains uncertain. PURPOSE: The primary
      purpose of this study is to assess whether improvements in HRQoL after surgical
      management of focal lumbar spinal stenosis (FLSS) with or without
      spondylolisthesis are sustainable over the long term compared with that of
      THA/TKA for OA. STUDY DESIGN: Single-center, retrospective, longitudinal matched
      cohort study of prospectively collected outcomes, with a minimum of 5-year follow
      up (FU). PATIENT SAMPLE: Patients who had primary one- to two-level spinal
      decompression with or without instrumented fusion for FLSS and THA/TKA for
      primary OA. OUTCOME MEASURES: Postoperative change from baseline to last FU in
      Short-Form 36 physical component summary (PCS) and mental component summary (MCS)
      scores among groups was used as the primary outcome measure. METHODS: An age, sex
      matched inception cohort of primary one- to two-level spinal decompression with
      or without instrumented fusion for FLSS (n=99) was compared with a cohort of
      primary THA (n=99) and TKA (n=99) for OA and followed for a minimum of 5 years.
      Linear regression was used for the primary analysis. RESULTS: Mean (percent) FUs
      in months were 80.5+16.04 (79%), 94.6+16.62 (92%), and 80.6+16.84 (85%) for the
      FLSS, THA, and TKA cohorts, respectively, with a range of 5 to 10 years for all
      three cohorts. The number of patients who have undergone revision including those
      lost to FU for the FLSS, THA, and TKA cohorts were n=20 (20.2%, same site [n=7]
      and adjacent segment [n=13]) requiring 27 operations, n=3 (3%, same site)
      requiring 5 operations, and n=8 (8.1%, same site) requiring 12 operations,
      respectively (p<.01). The average time to first revision was 56/65/43 months,
      respectively. Mean postoperative PCS (p<.0001) and MCS (p<.02) scores improved
      significantly and were durable for all groups at the last FU. The mean changes
      from baseline PCS/MCS scores to last FU were 8.5/6.4, 12.3/7.0, and 8.3/4.9 for
      FLSS, THA, and TKA, respectively. Adjusting for baseline age, sex, body mass
      index, PCS score, and MCS score, there was a strong trend in favor of greater
      sustained change in the PCS score of THA over FLSS (p=.07) and TKA (p=.08). No
      difference was noted for change in PCS score between FLSS and TKA (p=.95). No
      differences were noted for change in MCS score among all three cohorts (p>.1).
      CONCLUSIONS: Significant improvements in HRQoL after surgical treatment of FLSS
      with or without spondylolisthesis and hip and knee OA are sustained for a mean of
      7 to 8 years, with a minimum of 5-year FU. Despite a higher revision rate,
      patients undergoing surgery for FLSS can expect a comparable long-term average
      improvement in HRQoL from baseline compared with their peers undergoing TKA and
      to a lesser extent THA.

PMID- 24325881
TI  - Diagnostic accuracy of history taking to assess lumbosacral nerve root
      compression.
AB  - BACKGROUND CONTEXT: The diagnosis of sciatica is primarily based on history and
      physical examination. Most physical tests used in isolation show poor diagnostic
      accuracy. Little is known about the diagnostic accuracy of history items.
      PURPOSE: To assess the diagnostic accuracy of history taking for the presence of
      lumbosacral nerve root compression or disc herniation on magnetic resonance
      imaging in patients with sciatica. STUDY DESIGN: Cross-sectional diagnostic
      study. PATIENT SAMPLE: A total of 395 adult patients with severe disabling
      radicular leg pain of 6 to 12 weeks duration were included. OUTCOME MEASURES:
      Lumbosacral nerve root compression and disc herniation on magnetic resonance
      imaging were independently assessed by two neuroradiologists and one neurosurgeon
      blinded to any clinical information. METHODS: Data were prospectively collected
      in nine hospitals. History was taken according to a standardized protocol. There
      were no study-specific conflicts of interest. RESULTS: Exploring the diagnostic
      odds ratio of 20 history items revealed a significant contribution in diagnosing
      nerve root compression for "male sex," "pain worse in leg than in back," and "a
      non-sudden onset." A significant contribution to the diagnosis of a herniated
      disc was found for "body mass index <30," "a non-sudden onset," and "sensory
      loss." Multivariate logistic regression analysis of six history items pre
      selected from the literature (age, gender, pain worse in leg than in back,
      sensory loss, muscle weakness, and more pain on coughing/sneezing/straining)
      revealed an area under the receiver operating characteristic curve of 0.65 (95%
      confidence interval, 0.58-0.71) for the model diagnosing nerve root compression
      and an area under the receiver operating characteristic curve of 0.66 (95%
      confidence interval, 0.58-0.74) for the model diagnosing disc herniation.
      CONCLUSIONS: A few history items used in isolation had significant diagnostic
      value and the diagnostic accuracy of a model with six pre-selected items was
      poor.

PMID- 24325882
TI  - Psychometric properties of online administered parental strengths and
      difficulties questionnaire (SDQ), and normative data based on combined online and
      paper-and-pencil administration.
AB  - OBJECTIVE: To examine the psychometric properties of the online administered
      parental version of the Strength and Difficulties Questionnaire (SDQ), and to
      provide parental norms from a nationwide Swedish sample. METHODS: A total of 1443
      parents from of a national probability sample of 2800 children aged 10-13 years
      completed the SDQ online or as usual (i.e., using paper-and-pencil). RESULTS: The
      SDQ subscales obtained from the online administration showed high internal
      consistency (polychoric ordinal alpha), and confirmatory factor analysis of the
      SDQ five factor model resulted in excellent fit. The Total Difficulties score of
      the SDQ and its other subscales were significantly related to the Disruptive
      Behavior Disorders (DBD) rating scale. Norms for the parent version of SDQ
      obtained from the Internet were identical to those collected using paper-and
      pencil. They were thus combined and are presented sorted by child gender and age.
      CONCLUSIONS: The SDQ seems to be a reliable and valid instrument given its high
      internal consistency, clear factor structure and high correlation with other
      instruments capturing the intended constructs. Findings in the present study
      support its use for online data collection, as well as using norms obtained
      through paper-and-pencil-administration even when SDQ has been administrated
      online.

PMID- 24325883
TI  - Quantitative assessment of interradicular bone density in the maxilla and
      mandible: implications in clinical orthodontics.
AB  - BACKGROUND: Bone density at the interradicular area plays an important role
      during orthodontic treatment. In view of this fact, the study was designed to
      quantitatively evaluate the bone density at the interradicular areas of the
      alveolar and basal bones of maxilla and mandible by computed tomography. METHODS:
      One hundred and nine computed tomographic images were randomly selected, and bone
      density was measured in Hounsfield units (HU) with bone mineral density software
      (Siemens VA20A_SP3A). The sample consisted of 78 males (mean age 29.5 years,
      range 20 to 40 years) and 31 females (mean age 27.6 years, range 20 to 40 years).
      Cortical and cancellous bone density was measured at the interradicular areas at
      the alveolar and basal bone levels of the maxilla and mandible, and the data was
      subjected to statistical analysis for comparisons. RESULTS: The highest cortical
      bone density was observed between the second premolar and first molar at the
      alveolar bone level and between the first and second molars at the basal bone
      level in the maxilla. Maxillary tuberosity showed the least bone density. The
      density of the cortical bone was greater in the mandible than in the maxilla and
      showed a progressive increase from the incisor to the retromolar area. The basal
      bone showed a higher density thanthe alveolar bone. CONCLUSION: Different
      qualities of the bone were found in the anatomic regions studied, which confirms
      the importance of knowledge of site-specific bone tissue density to correlate
      with various clinical findings.

PMID- 24325885
TI  - Child survival: a message of hope but a call for renewed commitment in UNICEF
      report.
AB  - A recent UNICEF report Committing to Child Survival: A Promise Renewed Progress
      Report 2013 presents a comprehensive analysis of levels and trends in child
      mortality and progress towards MDG 4. The global under-five mortality rate has
      been cut nearly in half (47%) since 1990. However, during this same period, 216
      million children are estimated to have died before their fifth birthday. Most of
      these deaths were from leading infectious diseases such as pneumonia, diarrhoea
      or malaria, or were caused by preventable neonatal causes such as those related
      to intra-partum complications. The highest mortality rates in the world are
      observed in low-income countries in sub-Saharan Africa and South Asia. Sub
      Saharan Africa faces a particular challenge in that it not only has the highest
      under-five mortality in the world but it also has the fastest population growth.
      Progress is possible, however, and sharp reductions in child mortality have been
      observed at all levels of national income and in all regions. Some of the world's
      poorest countries in terms of national income have made the strongest gains in
      child survival. Within countries, new analysis suggests that disparities in under
      five mortality between the richest and the poorest households have declined in
      most regions of the world, with the exception of Sub-Saharan Africa. Furthermore,
      under-five mortality rates have fallen even among the poorest households in all
      regions. The report highlights the growing importance of neonatal deaths; roughly
      44% of global under-five deaths - now 2.9 million a year - occur during the
      neonatal period, with up to 50% dying during their first day of life and yet over
      two-thirds of these deaths are preventable without intensive care. The report
      stresses how a continuum of care approach across the whole life cycle is the most
      powerful way of understanding and accelerating further progress. 

PMID- 24325884
TI  - State of the science on controversial topics: missing maxillary lateral incisors-
      a report of the Angle Society of Europe 2012 meeting.
AB  - BACKGROUND: The optimal long-term management of the congenitally missing
      maxillary lateral incisor continues to cause controversy within the specialty.
      The Angle Society of Europe meeting 2012 dedicated a day to address some of the
      current controversies relating to the management of these missing lateral
      incisors. FINDINGS: The format of the day consisted of morning presentations and
      afternoon breakout sessions to discuss a variety of questions related to the
      management of missing lateral incisors. CONCLUSIONS: The consensus viewpoint from
      this day was that the care of patients with congenitally missing lateral incisors
      is best achieved through a multi-disciplinary approach. The current evidence base
      is weak, and further well-designed, prospective trials are needed.

PMID- 24325886
TI  - Frictional resistance in monocrystalline ceramic brackets with conventional and
      nonconventional elastomeric ligatures.
AB  - BACKGROUND: The objective of this study was to compare the frictional forces
      generated by three types of monocrystalline ceramic brackets coupled with
      conventional elastomeric ligatures (CEL) and nonconventional elastomeric
      ligatures (NCEL) during the alignment of apically displaced teeth at the
      maxillary arch. METHODS: All tests (a total of 480 tests) were carried out in a
      dry state on a universal testing machine with a testing model consisting of three
      0.022-in. monocrystalline ceramic preadjusted brackets (from the maxillary right
      second premolar through the right central incisor). The canine bracket was bonded
      to a sliding bar that allowed for different vertical positions. The frictional
      forces generated by a 0.012- and 0.014-in. superelastic nickel titanium wire
      (SENT) with conventional and nonconventional ligatures at various amounts of
      canine misalignment (1.5, 3.0, 4.5, and 6.0 mm) were recorded. Comparisons
      between the different types of bracket-wire-ligature systems were carried out by
      means of analysis of variance on ranks with Tukey's post hoc test (P<0.05).
      RESULTS: No significant differences were assessed among the three types of
      monocrystalline brackets with NCEL when coupled with 0.012-in. SENT. Radiance
      brackets with NCEL coupled with 0.014-in. SENT showed significantly greater
      frictional force than Inspire Ice brackets and Pure brackets with NCEL. A
      significantly greater amount of frictional force was generated with CEL when
      compared with NCEL for all the tested variables, with the exception of the Pure
      brackets with 0.012-in. SENT at 1.5 and 3.0 mm of canine misalignment where
      similar frictional forces were found. CONCLUSIONS: Nonconventional elastomeric
      ligatures are able to reduce friction in monocrystalline ceramic brackets.

PMID- 24325887
TI  - Role of rostral medulla in serotonin-induced changes of respiratory rhythm in
      newborn rat brainstem-spinal cord preparations.
AB  - Abnormalities of the serotonin (5-hydroxytryptamine, 5-HT) system may induce
      respiratory disorders. We examined which regions in the rostral medulla are
      important for the effect of 5-HT on the frequency of respiratory-like nerve (fR
      like) activity by transecting the preparations at different levels near the
      facial nucleus (nVII) in newborn rat brainstem-spinal cord preparations. The fR
      like activity at the fourth cervical ventral root (C4) of the Pons-medulla-spinal
      cord preparations in 2-3-day-old rats (n=25) was monitored at 26 degrees C, and
      the change in fR-like activity in response to application of 10MUM 5-HT before
      and after transection was compared among three groups, in which nVII was retained
      (group A, n=10), partially retained (group B, n=7), or eliminated (group C, n=8)
      by the transection. Before transection, the resting fR-like activity (set to
      100%) and stimulant effect of 5-HT (+101-143%) were similar among the groups.
      After transection, resting fR-like activity increased in all groups, but the
      facilitatory effects of 5-HT on the fR-like activity were abolished in groups A
      and C (fR-like activity of -4% and +7%, respectively). In group B, 5-HT became
      inhibitory (fR-like activity of -28%). In conclusion, a distinct part of the
      rostral medulla in the absence of pontine influences may mediate the inhibitory
      effects of 5-HT on the respiratory rhythm. 

PMID- 24325888
TI  - The prevalence of weight loss during (chemo)radiotherapy treatment for lung
      cancer and associated patient- and treatment-related factors.
AB  - BACKGROUND & AIMS: Thoracic radiotherapy is associated with toxicities that can
      adversely impact nutritional intake. This study aimed to investigate the
      prevalence and predictors of >=5% weight loss and commencement of enteral
      nutrition in lung cancer patients receiving radiotherapy. METHODS: A
      retrospective study of 96 patients treated with high dose palliative or radical
      radiotherapy for a primary diagnosis of small cell or non-small cell lung cancer.
      Weight loss was calculated between the start and up to 90 days from radiotherapy
      commencement. Associations between >=5% weight loss and enteral feeding, and
      demographic and clinical factors (age, gender, nutritional status, total dose of
      radiotherapy, concurrent chemotherapy, disease stage, prior surgery, hyper
      fractionation and performance status) were assessed. RESULTS: The prevalence of
      weight loss >=5% was 31% (median weight loss 8%, range 5-19%). The prevalence of
      commencement of enteral nutrition was 12%. Patients receiving concurrent
      chemotherapy were more likely to have >=5% weight loss (40 versus 0%, phi = 0.35,
      p < 0.001). The odds of a patient with late stage disease having >=5% weight loss
      were 15 times greater than for a patient with earlier disease stage (95% CI 1.97,
      122.8, p = 0.009). Only Patient Generated Subjective Global Assessment score was
      associated with starting enteral nutrition (r = 0.27, p = 0.03). CONCLUSION:
      Clinically significant weight loss is prevalent in lung cancer patients receiving
      radiotherapy and is associated with concurrent chemotherapy and late stage
      disease. Identification of factors associated with weight loss assists with early
      identification and intervention in patients at high nutritional risk.

PMID- 24325889
TI  - Blood donor recruitment strategies and their impact on blood safety in Egypt.
AB  - INTRODUCTION: Because of the high incidence of HCV, blood safety presents a
      serious challenge in Egypt. Given the constrained economy which limits the
      implementation of nucleic acid amplification technology, proper recruitment of
      blood donors becomes of paramount importance. To evaluate the effectiveness of
      blood donor recruitment strategies, the seroprevalence of positive infectious
      markers among blood donors was studied. MATERIALS AND METHODS: Donors' records
      covering the period from 2006-2012 were reviewed. Blood donations were screened
      for HCV antibodies, HBs antigen (HBsAg), HIV-1 and 2 and syphilis antibodies.
      RESULTS: Of 308,762 donors, 63.4% were voluntary donors (VD). VD of 2011-2012
      were significantly younger than family replacement donors (RD) .The overall
      prevalences of HCV antibodies, HBsAg, HIV and syphilis antibodies were 4.3%,
      1.22%, 0.07%, and 0.13%, respectively. All tested markers (except HIV) were
      significantly higher among RD, when compared to VD (P<0.0001). A consistent
      steady trend for decrease in HCV seropositivity was observed in RD and VD from
      8.9% and 4.2% to 3.8% and 1.5%, respectively. A trend for decrease in HBsAg was
      demonstrated in VD from 1.2% to 0.53%. CONCLUSION: The decreasing trends in HCV
      antibody and HBs antigen is promising and may reflect the improved donor
      selection criteria.

PMID- 24325890
TI  - Successful management of acute bleeding in essential thrombocythemia using
      automated cell separator.
AB  - This case represents the challenging role of automated cell separators in
      management of acute hemorrhagic crisis in a young female patient of essential
      thrombocythemia. A 17 year old girl having body weight of 41 kg presented to us
      with profuse nasal bleed. Complete blood counts revealed extremely high platelet
      counts of 2987*10(9)/l. Due to no response by oral hydroxyurea for last 2 months,
      urgent mechanical platelet reduction was planned to prevent further complication.
      A rebound phenomenon of increase in circulating platelet count was observed after
      every therapeutic platelet reduction. Seven procedures had to be performed on
      alternate days to bring down the platelet counts to less than 600*10(9)/l.
      Patient was maintained on oral anagrelide therapy and discharged in a stable
      condition after 14 days. Therapeutic platelet reduction causes rapid platelet
      reduction and helps in managing acute complications.

PMID- 24325891
TI  - Properties of the Driving Behavior Survey among individuals with motor vehicle
      accident-related posttraumatic stress disorder.
AB  - Data suggest anxious drivers may engage in problematic behaviors that place
      themselves and others at increased risk of negative traffic events. Three domains
      of problematic behavior--exaggerated safety/caution, performance deficits, and
      hostile/aggressive behaviors--previously were identified during development of
      the Driving Behavior Survey (DBS), a novel measure of anxiety-related behavior.
      Extending this research, the current study examined the psychometric properties
      of DBS scores among individuals with posttraumatic stress disorder (PTSD)
      subsequent to motor vehicle trauma (N=40). Internal consistencies and 12-week
      test-retest reliabilities for DBS scales ranged from good to excellent.
      Comparison of scores to normative student data indicated dose-response
      relationships for safety/caution and performance deficit subscales, with
      increased frequency of anxious behavior occurring within the PTSD sample.
      Associations with standard clinical measures provide additional evidence for
      anxiety-related driving behavior as a unique marker of functional impairment,
      distinct from both avoidance and disorder-specific symptoms.

PMID- 24325892
TI  - Does early repair of congenital heart disease increase the rate of ADHD symptoms?
      Additional information is necessary to provide an answer.

PMID- 24325893
TI  - Reintroduction of the invasive mosquito species Aedes albopictus in Belgium in
      July 2013.
AB  - Since its first report in 2000, the invasive mosquito Aedes albopictus was not
      found any more during the different entomological inspections performed at its
      place of introduction in Belgium between 2001 and 2012. In July 2013, one adult
      male was captured at the same site (a platform of imported used tires located in
      Vrasene, Oost-Vlaanderen Province), during a monitoring using CO2-baited trap.
      This finding suggests the reintroduction of the species in Belgium via the used
      tire trade. 

PMID- 24325894
TI  - Primary lymphoma of the uterine horn in a Lhasa Apso dog.
AB  - Primary lymphomas of the canine female genital tract are uncommon tumours. A 9
      year-old intact female Lhasa Apso dog presenting with a closed pyometra underwent
      an ovariohysterectomy (OHE), and the hyperplastic uterine horn along with
      multiple follicular cysts on the right ovary was examined by histological
      analysis. Severe infiltration of medium-sized lymphocytes with strong positive
      immunoreactivity for CD79a and numerous anaplastic features was detected in the
      unilateral uterine horn, and the dog was diagnosed as having extranodal marginal
      zone B-cell lymphoma (MZBCL). The present case reports an extremely rare
      occurrence of primary lymphoma involving the uterine horn in a dog and describes
      histological characteristics of the tumour for definite diagnosis. 

PMID- 24325895
TI  - The "cytokine for gerontologists" has some company.

PMID- 24325896
TI  - Association between insulin resistance and low relative appendicular skeletal
      muscle mass: evidence from a cohort study in community-dwelling older men and
      women participants.
AB  - BACKGROUND: It has been hypothesized that insulin resistance plays a role in the
      development of the loss of skeletal muscle; however, no cohort studies on insulin
      resistance and low relative appendicular skeletal muscle mass (ASM) have been
      published to date. Thus, we examined whether insulin resistance is associated
      with low relative ASM after a 4.6-year follow-up period among apparently healthy
      older men and women participants. METHODS: This is a combined retrospective
      prospective cohort study, which includes 147 community-dwelling older men and
      women participants. ASM was measured by dual-energy x-ray absorptiometry at
      baseline and follow-up. Participants with a relative change in ASM below the sex
      specific 15th value were classified as the low relative ASM group. Homeostatic
      model assessment was used to quantify insulin resistance. Logistic regression
      calculated odds ratios and 95% confidence intervals for development of low
      relative ASM, adjusted for covariates. RESULTS: The loss of ASM in the low
      relative ASM and normal groups was -1.8kg and -0.35kg, respectively (p <= .05).
      The low relative ASM group was older and had higher insulin and homeostatic model
      assessment of insulin resistance values at baseline. The risk of developing low
      relative ASM at 4.6-year follow-up was 2.9 times higher (95% CI, 1.00-7.8; p =
      .04) among the participants with homeostatic model assessment of insulin
      resistance levels more than 2.3. After adjusting for age, the risk increased to
      3.9 times higher (95% CI, 1.3-11.5; p = .03). CONCLUSION: Insulin resistance was
      associated with low relative ASM at 4.6-year follow-up after accounting for
      several covariates in a cohort of apparently healthy, well-functioning young
      older men and women.

PMID- 24325897
TI  - Are glycans the Holy Grail for biomarkers of aging?
AB  - Posttranslational modifications of circulating proteins such as immunoglobulins
      may prove to be important biomarkers of aging.

PMID- 24325898
TI  - Glycans are a novel biomarker of chronological and biological ages.
AB  - Fine structural details of glycans attached to the conserved N-glycosylation site
      significantly not only affect function of individual immunoglobulin G (IgG)
      molecules but also mediate inflammation at the systemic level. By analyzing IgG
      glycosylation in 5,117 individuals from four European populations, we have
      revealed very complex patterns of changes in IgG glycosylation with age. Several
      IgG glycans (including FA2B, FA2G2, and FA2BG2) changed considerably with age and
      the combination of these three glycans can explain up to 58% of variance in
      chronological age, significantly more than other markers of biological age like
      telomere lengths. The remaining variance in these glycans strongly correlated
      with physiological parameters associated with biological age. Thus, IgG
      glycosylation appears to be closely linked with both chronological and biological
      ages. Considering the important role of IgG glycans in inflammation, and because
      the observed changes with age promote inflammation, changes in IgG glycosylation
      also seem to represent a factor contributing to aging. SIGNIFICANCE STATEMENT:
      Glycosylation is the key posttranslational mechanism that regulates function of
      immunoglobulins, with multiple systemic repercussions to the immune system. Our
      study of IgG glycosylation in 5,117 individuals from four European populations
      has revealed very extensive and complex changes in IgG glycosylation with age.
      The combined index composed of only three glycans explained up to 58% of variance
      in age, considerably more than other biomarkers of age like telomere lengths. The
      remaining variance in these glycans strongly correlated with physiological
      parameters associated with biological age; thus, IgG glycosylation appears to be
      closely linked with both chronological and biological ages. The ability to
      measure human biological aging using molecular profiling has practical
      applications for diverse fields such as disease prevention and treatment, or
      forensics.

PMID- 24325900
TI  - Imaging in thoracic oncology: case studies from Multidisciplinary Thoracic Tumor
      Board (part 1 of 2 part series).
AB  - Multidisciplinary tumor board conferences foster collaboration among health care
      providers from a variety of specialties and help to facilitate optimal patient
      care. Typical cases from thoracic tumor board conferences include patients with
      known or suspected bronchogenic and esophageal carcinomas, as well as less common
      diseases such as thymomas and mesotheliomas. In most instances, the clinical
      questions revolve around the best options for establishing a diagnosis, staging
      the disease and directing treatment. This article describes and illustrates the
      clinical scenarios of three patients who were presented at our tumor board,
      focusing on management issues and the role of imaging. These patients had non
      small cell lung cancer and mediastinal lymph node metastases; a small, growing
      ground glass nodule; and oligometastatic non-small cell lung cancer,
      respectively. 

PMID- 24325899
TI  - Randomized study comparing use of THUNDERBEAT technology vs standard
      electrosurgery during laparoscopic radical hysterectomy and pelvic
      lymphadenectomy for gynecologic cancer.
AB  - STUDY OBJECTIVE: To compare operative time with use of THUNDERBEAT (TB) vs
      standard electrosurgery (SES) during laparoscopic radical hysterectomy and pelvic
      lymphadenectomy to treat gynecologic tumors. DESIGN: Evidence obtained from a
      properly designed, randomized, controlled trial (Canadian Task Force
      classification I). SETTING: Gynecologic Oncology Unit of the Catholic University
      of the Sacred Heart in Rome, Italy. PATIENTS: Fifty patients with early cervical
      cancer (FIGO stages IA2, IB1, IIA <2 cm) or locally advanced cervical cancer
      (FIGO stages IB2, IIA >2cm, IIB) who received neoadjuvant treatment (chemotherapy
      or radiochemotherapy) and demonstrated a complete or partial clinical response
      and early stage endometrioid endometrial cancer (FIGO stages IB, II) were
      randomly assigned to undergo TB (arm A) or SES (arm B). INTERVENTION:
      Laparoscopic radical hysterectomy with bilateral pelvic lymphadenectomy, using an
      easily reproducible technique was performed. MEASUREMENTS AND MAIN RESULTS: Fifty
      patients were available for analysis, with 25 women randomly assigned to TB (arm
      A) and 25 to SES (arm B). The median operative time was 85 minutes for TB vs 115
      minutes for SES (p = .001). At multivariate analysis, endometrial cancer (p =
      .001) and TB (p = .001) were independently associated with shorter operating
      time. No differences in perioperative outcomes and postoperative complications
      were observed between the 2 arms. Patients who underwent TB reported less
      postoperative pain, both at rest (p = .005) and after the Valsalva maneuver (p =
      .008), with less additional analgesic therapy other than standard therapy
      required in patients who underwent SES (p = .02). CONCLUSION: TB is associated
      with shorter operative time and less postoperative pain than is the standard
      technique (SES) in patients with uterine cancer.

PMID- 24325901
TI  - Assembly of eukaryotic algal chromosomes in yeast.
AB  - BACKGROUND: Synthetic genomic approaches offer unique opportunities to use
      powerful yeast and Escherichia coli genetic systems to assemble and modify
      chromosome-sized molecules before returning the modified DNA to the target host.
      For example, the entire 1 Mb Mycoplasma mycoides chromosome can be stably
      maintained and manipulated in yeast before being transplanted back into recipient
      cells. We have previously demonstrated that cloning in yeast of large (> ~ 150
      kb), high G + C (55%) prokaryotic DNA fragments was improved by addition of yeast
      replication origins every ~100 kb. Conversely, low G + C DNA is stable (up to at
      least 1.8 Mb) without adding supplemental yeast origins. It has not been
      previously tested whether addition of yeast replication origins similarly
      improves the yeast-based cloning of large (>150 kb) eukaryotic DNA with moderate
      G + C content. The model diatom Phaeodactylum tricornutum has an average G + C
      content of 48% and a 27.4 Mb genome sequence that has been assembled into
      chromosome-sized scaffolds making it an ideal test case for assembly and
      maintenance of eukaryotic chromosomes in yeast. RESULTS: We present a modified
      chromosome assembly technique in which eukaryotic chromosomes as large as ~500 kb
      can be assembled from cloned ~100 kb fragments. We used this technique to clone
      fragments spanning P. tricornutum chromosomes 25 and 26 and to assemble these
      fragments into single, chromosome-sized molecules. We found that addition of
      yeast replication origins improved the cloning, assembly, and maintenance of the
      large chromosomes in yeast. Furthermore, purification of the fragments to be
      assembled by electroelution greatly increased assembly efficiency. CONCLUSIONS:
      Entire eukaryotic chromosomes can be successfully cloned, maintained, and
      manipulated in yeast. These results highlight the improvement in assembly and
      maintenance afforded by including yeast replication origins in eukaryotic DNA
      with moderate G + C content (48%). They also highlight the increased efficiency
      of assembly that can be achieved by purifying fragments before assembly.

PMID- 24325902
TI  - Burst and principal components analyses of MEA data for 16 chemicals describe at
      least three effects classes.
AB  - Microelectrode arrays (MEAs) can be used to detect drug and chemical induced
      changes in neuronal network function and have been used for neurotoxicity
      screening. As a proof-of-concept, the current study assessed the utility of
      analytical "fingerprinting" using principal components analysis (PCA) and
      chemical class prediction using support vector machines (SVMs) to classify
      chemical effects based on MEA data from 16 chemicals. Spontaneous firing rate in
      primary cortical cultures was increased by bicuculline (BIC), lindane (LND), RDX
      and picrotoxin (PTX); not changed by nicotine (NIC), acetaminophen (ACE), and
      glyphosate (GLY); and decreased by muscimol (MUS), verapamil (VER), fipronil
      (FIP), fluoxetine (FLU), chlorpyrifos oxon (CPO), domoic acid (DA), deltamethrin
      (DELT) and dimethyl phthalate (DMP). PCA was performed on mean firing rate,
      bursting parameters and synchrony data for concentrations above each chemical's
      EC50 for mean firing rate. The first three principal components accounted for
      67.5, 19.7, and 6.9% of the data variability and were used to identify separation
      between chemical classes visually through spatial proximity. In the PCA, there
      was clear separation of GABAA antagonists BIC, LND, and RDX from other chemicals.
      For the SVM prediction model, the experiments were classified into the three
      chemical classes of increasing, decreasing or no change in activity with a mean
      accuracy of 83.8% under a radial kernel with 10-fold cross-validation. The
      separation of different chemical classes through PCA and high prediction accuracy
      in SVM of a small dataset indicates that MEA data may be useful for separating
      chemicals into effects classes using these or other related approaches. 

PMID- 24325903
TI  - Mini-implants and the efficiency of Herbst treatment: a preliminary study.
AB  - BACKGROUND: The purpose of this study is to present the use of a modified Herbst
      appliance in association with temporary anchorage devices (TADs) in order to
      enhance the correction of skeletal class II malocclusions. METHODS: Ten
      consecutive adolescents scheduled for Herbst treatment were assigned to two
      treatment groups. Five cases were treated with a modified miniscrew-supported
      Herbst appliance (experimental group (EG)) and five cases with a conventional
      cast Herbst appliance (control group (CG)). In all cases, the Herbst was kept in
      place for 9 months and was followed by fixed appliances until class I
      relationships were achieved. The initial (T1) and final (T2) lower incisor
      inclination on lateral headfilms were analyzed for each case, and the mean
      increase for the five EG patients and the five CG patients were compared.
      RESULTS: The mean increase in lower incisor inclination at the end of treatment
      was 1 degrees  (range 0 degrees  to 2 degrees ) for the EG and 7 degrees  (range
      4 degrees  to 10 degrees ) for the CG. CONCLUSIONS: The rational association of
      TADs with the Herbst appliance can optimize treatment efficiency and skeletal
      response by reducing the occurrence of excessive lower incisor proclination.

PMID- 24325904
TI  - Comparison of shear bond strength and adhesive remnant index between precoated
      and conventionally bonded orthodontic brackets.
AB  - BACKGROUND: The purpose of this study was to compare the shear bond strength and
      adhesive remnant index (ARI) at the enamel-bonding interface of precoated and
      conventionally bonded brackets, utilizing standardized procedures. METHODS: The
      test sample consisted of 90 recently extracted bovine permanent mandibular
      incisors. The teeth were bonded using the same protocol and were tested in three
      different situations. A material testing systems machine was utilized for
      debonding, and the remaining adhesive on the tooth was recorded. RESULTS:
      Immediately after bonding, we found that the shear bond strength of the precoated
      brackets (6.27 MPa) was significantly higher than that of conventional brackets
      (5.37 MPa) (p<0.05). However, no significant differences in bond strength were
      found between the two bracket systems after 24 h of bonding or after
      thermocycling. The conventional brackets had higher ARI scores than the precoated
      bracket systems immediately after bonding and after 24 h. CONCLUSIONS: Since
      there were no significant differences in the bonding strength after 24 h, the
      immediate bonding strength of the precoated brackets during the first day does
      not appear to be a major advantage over the conventional bracket systems.
      However, less adhesive on the tooth after debonding is an advantage of precoated
      brackets.

PMID- 24325905
TI  - Preliminary experience with the use of an autologous platelet-rich fibrin
      membrane for urethroplasty coverage in distal hypospadias surgery.
AB  - OBJECTIVE: Platelet-rich fibrin (PRF) has been shown to have structural and
      biological properties that promote tissue healing. This prospective study
      evaluated the feasibility, safety, and efficiency of using autologous PRF
      membrane for urethroplasty coverage in distal hypospadias. MATERIALS AND METHODS:
      We prospectively included 33 patients with distal hypospadias operated on between
      June 2010 and September 2011. Urethroplasties were performed using the Duplay
      technique. During surgery, 5-10 ml of patient's blood was collected and
      immediately centrifuged. A PRF clot was transformed into a dense fibrin membrane
      with a particular cell content and architecture. This membrane was applied and
      sutured over the urethroplasty. The perioperative course and complications were
      recorded. Outcomes were compared with those in a control group of children
      undergoing the same procedure, but with another mean of coverage. RESULTS: With a
      median follow-up of 8 months (range, 6-18 months), urethral fistula occurred in
      2/33 patients. No other complication was noted. No complication related to the
      blood sampling was reported. There was no statistically significant difference
      with the control group (p = 0.65). CONCLUSION: The PRF patch seems to be a safe
      and efficient covering technique. Thus, procedure is an additional approach to
      coverage for hypospadias surgery, and may help to reduce the incidence of
      postoperative complications when coverage healthy tissue is not available.

PMID- 24325906
TI  - Myogenesis of Malacostraca - the "egg-nauplius" concept revisited.
AB  - BACKGROUND: Malacostracan evolutionary history has seen multiple transformations
      of ontogenetic mode. For example direct development in connection with extensive
      brood care and development involving planktotrophic nauplius larvae, as well as
      intermediate forms are found throughout this taxon. This makes the Malacostraca a
      promising group for study of evolutionary morphological diversification and the
      role of heterochrony therein. One candidate heterochronic phenomenon is
      represented by the concept of the 'egg-nauplius', in which the nauplius larva,
      considered plesiomorphic to all Crustacea, is recapitulated as an embryonic
      stage. RESULTS: Here we present a comparative investigation of embryonic muscle
      differentiation in four representatives of Malacostraca: Gonodactylaceus falcatus
      (Stomatopoda), Neocaridina heteropoda (Decapoda), Neomysis integer (Mysida) and
      Parhyale hawaiensis (Amphipoda). We describe the patterns of muscle precursors in
      different embryonic stages to reconstruct the sequence of muscle development,
      until hatching of the larva or juvenile. Comparison of the developmental
      sequences between species reveals extensive heterochronic and heteromorphic
      variation. Clear anticipation of muscle differentiation in the nauplius segments,
      but also early formation of longitudinal trunk musculature independently of the
      teloblastic proliferation zone, are found to be characteristic to stomatopods and
      decapods, all of which share an egg-nauplius stage. CONCLUSIONS: Our study
      provides a strong indication that the concept of nauplius recapitulation in
      Malacostraca is incomplete, because sequences of muscle tissue differentiation
      deviate from the chronological patterns observed in the ectoderm, on which the
      egg-nauplius is based. However, comparison of myogenic sequences between taxa
      supports the hypothesis of a zoea-like larva that was present in the last common
      ancestor of Eumalacostraca (Malacostraca without Leptostraca). We argue that much
      of the developmental sequences of larva muscle patterning were retained in the
      eumalacostracan lineage despite the reduction of free swimming nauplius larvae,
      but was severely reduced in the peracaridean clade.

PMID- 24325907
TI  - Effects of short chain fatty acid producing bacteria on epigenetic regulation of
      FFAR3 in type 2 diabetes and obesity.
AB  - The human gut microbiota and microbial influences on lipid and glucose
      metabolism, satiety, and chronic low-grade inflammation are known to be involved
      in metabolic syndrome. Fermentation end products, especially short chain fatty
      acids, are believed to engage the epigenetic regulation of inflammatory reactions
      via FFARs (free fatty acid receptor) and other short chain fatty acid receptors.
      We studied a potential interaction of the microbiota with epigenetic regulation
      in obese and type 2 diabetes patients compared to a lean control group over a
      four month intervention period. Intervention comprised a GLP-1 agonist (glucagon
      like peptide 1) for type 2 diabetics and nutritional counseling for both
      intervention groups. Microbiota was analyzed for abundance, butyryl-CoA:acetate
      CoA-transferase gene and for diversity by polymerase chain reaction and 454 high
      throughput sequencing. Epigenetic methylation of the promoter region of FFAR3 and
      LINE1 (long interspersed nuclear element 1) was analyzed using bisulfite
      conversion and pyrosequencing. The diversity of the microbiota as well as the
      abundance of Faecalibacterium prausnitzii were significantly lower in obese and
      type 2 diabetic patients compared to lean individuals. Results from Clostridium
      cluster IV and Clostridium cluster XIVa showed a decreasing trend in type 2
      diabetics in comparison to the butyryl-CoA:acetate CoA-transferase gene and
      according to melt curve analysis. During intervention no significant changes were
      observed in either intervention group. The analysis of five CpGs in the promoter
      region of FFAR3 showed a significant lower methylation in obese and type 2
      diabetics with an increase in obese patients over the intervention period. These
      results disclosed a significant correlation between a higher body mass index and
      lower methylation of FFAR3. LINE-1, a marker of global methylation, indicated no
      significant differences between the three groups or the time points, although
      methylation of type 2 diabetics tended to increase over time. Our results provide
      evidence that a different composition of gut microbiota in obesity and type 2
      diabetes affect the epigenetic regulation of genes. Interactions between the
      microbiota and epigenetic regulation may involve not only short chain fatty acids
      binding to FFARs. Therefore dietary interventions influencing microbial
      composition may be considered as an option in the engagement against metabolic
      syndrome.

PMID- 24325908
TI  - Analysis of DNA repair gene polymorphisms in glioblastoma.
AB  - BACKGROUND: Glioblastoma is the most common and aggressive primary brain tumor in
      adults. Despite several factors such as ionizing radiation exposure or rare
      genetic syndromes have been associated with the development of glioblastoma, no
      underlying cause has been identified for the majority of cases. We thus aimed to
      investigate the role of DNA repair polymorphisms in modulating glioblastoma risk.
      METHODS: Genotypic and allelic frequencies of seven common polymorphisms in DNA
      repair genes involved in nucleotide excision repair (ERCC1 rs11615, ERCC2
      rs13181, ERCC6 rs4253079), base excision repair (APEX1 rs1130409, XRCC1 rs25487),
      double-strand break repair (XRCC3 rs861539) and mismatch repair (MLH1 rs1800734)
      pathways were analyzed in 115 glioblastoma patients and 200 healthy controls.
      Haplotype analysis was also performed for ERCC1 rs11615 and ERCC2 rs13181
      polymorphisms, located on the same chromosomal region (19q13.32). RESULTS: Our
      results indicated that carriers of the ERCC2 Gln/Gln genotype were associated
      with a lower glioblastoma risk (OR=0.32, 95% CI 0.12-0.89; P=0.028), whereas
      carriers of the MLH1 AA genotype were associated with an increased risk of
      glioblastoma (OR=3.14, 95% CI 1.09-9.06; P=0.034). Furthermore, the haplotype
      containing the C allele of ERCC2 rs13181 polymorphism and the T allele of ERCC1
      rs11615 polymorphism was significantly associated with a protective effect of
      developing glioblastoma (OR=0.34, 95% CI 0.16-0.71; P=0.004). CONCLUSIONS: These
      results pointed out that MLH1 rs1800734 and ERCC2 rs13181 polymorphisms might
      constitute glioblastoma susceptibility factors, and also suggested that the
      chromosomal region 19q could be important in glioblastoma pathogenesis.

PMID- 24325909
TI  - Genetic variation rs10484761 on 6p21.1 derived from a genome-wide association
      study is associated with gastric cancer survival in a Chinese population.
AB  - A recent genome-wide association study (GWAS) on esophageal squamous-cell
      carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide
      polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP
      rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP
      rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan
      Meier survival analysis, log-rank test, and Cox proportional hazard models were
      used to evaluate the association between the SNP rs10484761 and gastric cancer
      survival. In the dominant model, those who carry TC/CC genotypes had a
      significant shorter survival time (log-rank P=0.005), especially in the subgroups
      of aged male patients, cardia intestinal tumor (HR=1.41, 95% CI=1.08-1.84 for
      cardia cancer and HR=1.64, 95% CI=1.14-2.37 for intestinal-type), tumor size <= 5
      cm (HR=1.41, 95% CI=0.56-0.99), T1 depth invasion (HR=2.34, 95% CI=1.20-4.56),
      lymph node metastasis (HR=1.51, 95% CI=1.19-1.96), no distant metastasis
      (HR=1.33, 95% CI=1.05-1.68), TNM stage III+IV (HR=1.50, 95% CI=1.13-1.98), and
      with chemotherapy (HR=1.53, 95% CI=1.17-1.99). The results indicated that SNP
      rs10484761 was associated with prognosis of gastric cancer, suggesting that this
      genetic variant may serve as a potential marker to predict the survival of
      gastric cancer in Chinese population.

PMID- 24325910
TI  - Should interventions to treat or prevent Alzheimer's disease be tested in a
      population or as targeted treatment of highly selected study participants?
AB  - Symptomatic treatments for Alzheimer's disease should retain a place in the
      advanced stages of disease since their actions on these symptoms, even if not
      modifying the course of disease, are critical for improving patients' comfort and
      reducing the burden felt by caregivers, especially those facing behavioral
      disorders. In mild or prodromal stages, the opportunity to act on specific
      pathophysiological targets should be considered. These targeted and tailored
      therapies have the greatest chance to be active in the early stages of disease,
      in the context of heterogeneous pathological mechanisms to be specified by
      reliable and accessible biomarkers. Finally, interventional approaches in large
      populations seem particularly appropriate for prevention strategies. 

PMID- 24325911
TI  - Meta-analysis on the efficacy of tourniquet on ankle trauma surgery.
AB  - BACKGROUND: In our study, we used meta-analysis to study the efficacy of the
      tourniquet on ankle trauma surgery. Postoperative infection rate, deep venous
      thrombosis incidence, hospital stay, and joint range of motion were studied to
      compare the tourniquet and non-tourniquet groups and provide certain references
      for clinical decision. METHODS: We searched PubMed, MEDLINE, EMBASE, and the
      Cochrane controlled trials register for all publications about the efficacy of
      tourniquet published before November 2012. The quality of included studies was
      evaluated by two estimators. I2-test and Q-statistic were used for heterogeneity
      analysis. When there was heterogeneity between studies, the random effects model
      analysis was applied or else the fixed effects model analysis was used. RESULTS:
      Three studies were included with 166 patients suffering from ankle trauma
      surgery. There was no statistical difference (P >0.05) between the tourniquet and
      non-tourniquet groups on operation time (mean difference (MD) -5.45, 95%
      confidence intervals (CI): (-13.98, 3.09)), postoperative infection rate
      (relative risk (RR) 1.83, 95% CI: (0.65, 5.12)), and deep venous thrombosis
      incidence (RR 4.13, 95% CI: (0.47, 36.17)). But statistical significances were
      observed on hospital stays (MD 3.17, 95% CI: (1.39, 4.95)) and joint range of
      motion (MD - 5.25, 95% CI: (-9.61, -0.89)). CONCLUSIONS: In general, the efficacy
      of the tourniquet group is comparable to that of the non-tourniquet group. The
      non-tourniquet group achieved greater benefits for the joint range of motion and
      reduced the hospital stay. However, a larger number of primary studies is still
      required for future evaluation of tourniquet efficacy on ankle trauma surgery.

PMID- 24325912
TI  - The stem cell factor SOX2 regulates the tumorigenic potential in human gastric
      cancer cells.
AB  - Gastric cancer (GC) is still one of the most common causes of cancer-related
      death worldwide, which is mainly attributable to late diagnosis and poor
      treatment options. Infection with Helicobacter pylori, different environmental
      factors and genetic alterations are known to influence the risk of developing
      gastric tumors. However, the molecular mechanisms involved in gastric
      carcinogenesis are still not fully understood, making it difficult to design
      targeted therapeutic approaches. Aberrant expression of the specific gastric
      differentiation marker SOX2 has been observed in stomach cancer. However, the
      role of SOX2 in gastric tumors has not been well established to date. To
      elucidate the role of SOX2 in gastric tumorigenesis, SOX2 transcriptional
      activity was blocked in AZ-521 cells. Interestingly, inhibition of SOX2 reduced
      cell proliferation and migration, increased apoptosis and induced changes in cell
      cycle. Blocking of SOX2 also reduced the tumorigenic potential of AZ-521 cells in
      vivo. In addition, correlation of SOX2 expression and proliferation was observed
      in a subset of human gastric tumors. Finally, target genes of SOX2 were for the
      first time identified by RNA microarray in GC cells. Taken together, the results
      presented here indicate that SOX2 controls several aspects related to GC
      development and progression by regulating the expression of members of important
      signaling pathways. These findings could provide new therapeutic options for a
      subset of GCs exhibiting SOX2 deregulation. 

PMID- 24325913
TI  - FAT10, an ubiquitin-like protein, confers malignant properties in non-tumorigenic
      and tumorigenic cells.
AB  - FAT10 (HLA-F-adjacent transcript 10) is an ubiquitin-like modifier, which has
      been implicated in immune response and cancer development. In particular, the
      hypothesis of FAT10 as a mediator of tumorigenesis stems from its ability to
      associate with a spindle checkpoint protein Mad2 during mitosis and cause
      aneuploidy, a hallmark of cancer cells. Furthermore, FAT10 is overexpressed in
      several carcinomas types, including that of liver and colon. Nevertheless, direct
      evidence linking FAT10 to cell malignant transformation and progression is
      lacking. Here, we demonstrate that high FAT10 expression enhanced the
      proliferative, invasive, migratory and adhesive functions of the transformed cell
      line, HCT116. These observations were consistently demonstrated in an
      immortalized, non-tumorigenic liver cell line NeHepLxHT. Importantly, FAT10 can
      induce malignant transformation as evidenced from the anchorage-independent
      growth as well as in vivo tumor-forming abilities of FAT10-overexpressing
      NeHepLxHT cells, whereas in rapidly proliferating HCT116, increased FAT10 further
      augmented tumor growth. FAT10 was found to activate nuclear factor-kappaB
      (NFkappaB), which in turn upregulated the chemokine receptors CXCR4 and CXCR7.
      Importantly, small interfering RNA depletion of CXCR7 and CXCR4 attenuated cell
      invasion of FAT10-overexpressing cells, indicating that the CXCR4/7 is crucial
      for the FAT10-dependent malignant phenotypes. Taken together, our data reveal
      novel functions of FAT10 in malignant transformation and progression, via the
      NFkappaB-CXCR4/7 pathway. 

PMID- 24325914
TI  - A genome-wide gene-gene interaction analysis identifies an epistatic gene pair
      for lung cancer susceptibility in Han Chinese.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. By now,
      genome-wide association studies (GWAS) have identified numerous loci associated
      with the risk of developing lung cancer. However, these loci account for only a
      small fraction of the familial lung cancer risk. We hypothesized that epistasis
      may contribute to the missing heritability. To test this hypothesis, we
      systematically evaluated the association of epistasis of genetic variants with
      risk of lung cancer in Han Chinese cohorts. We conducted a pairwise genetic
      interaction analysis of 591370 variants, using BOolean Operation-based Screening
      and Testing (BOOST), in an ongoing GWAS of lung cancer that includes 2331 cases
      and 3077 controls. Pairs of epistatic loci with P BOOST <= 1.00*10(-6) were
      further evaluated by a logistic regression model (LRM) with covariate adjustment.
      Four promising epistatic pairs identified at the screening stage (P LRM <=
      2.86*10(-) (13)) were validated in two replication cohorts: the first from
      Beijing (1534 cases and 1489 controls) and the second from Shenyang and Guangzhou
      (2512 cases and 2449 controls). Using this combined analysis, we identified an
      interaction between rs2562796 and rs16832404 at 2p32.2 that was significantly
      associated with the risk of developing lung cancer (P LRM = 1.03*10(-13) in total
      13 392 subjects). This study is the first investigation of epistasis for lung
      cancer on a genome-wide scale in Han Chinese. It addresses part of the missing
      heritability in lung cancer risk and provides novel insight into the
      multifactorial etiology of lung cancer.

PMID- 24325916
TI  - Integrative genomics analysis reveals the multilevel dysregulation and oncogenic
      characteristics of TEAD4 in gastric cancer.
AB  - Tumorigenesis is a consequence of failures of multistep defense mechanisms
      against deleterious perturbations that occur at the genomic, epigenomic,
      transcriptomic and proteomic levels. To uncover previously unrecognized genes
      that undergo multilevel perturbations in gastric cancer (GC), we integrated
      epigenomic and transcriptomic approaches using two recently developed tools: MENT
      and GENT. This integrative analysis revealed that nine Hippo pathway-related
      genes, including components [FAT, JUB, LATS2, TEA domain family member 4 (TEAD4)
      and Yes-associated protein 1 (YAP1)] and targets (CRIM1, CYR61, CTGF and ITGB2),
      are concurrently hypomethylated at promoter CpG sites and overexpressed in GC
      tissues. In particular, TEAD4, a link between Hippo pathway components and
      targets, was significantly hypomethylated at CpG site cg21637033 (P = 3.8 * 10(-)
      (20)) and overexpressed (P = 5.2 * 10(-) (10)) in 108 Korean GC tissues compared
      with the normal counterparts. A reduced level of methylation at the TEAD4
      promoter was significantly associated with poor outcomes, including large tumor
      size, high-grade tumors and low survival rates. Compared with normal tissues, the
      TEAD4 protein was more frequently found in the nuclei of tumor cells along with
      YAP1 in 53 GC patients, demonstrating the posttranslational activation of this
      protein. Moreover, the knockdown of TEAD4 resulted in the reduced growth of GC
      cells both in vitro and in vivo. Finally, chromatin immunoprecipitation
      sequencing and microarray analysis revealed the oncogenic properties of TEAD4 and
      its novel targets (ADM, ANG, ARID5B, CALD1, EDN2, FSCN1 and OSR2), which are
      involved in cell proliferation and migration. In conclusion, the multilevel
      perturbations of TEAD4 at epigenetic, transcriptional and posttranslational
      levels may contribute to GC development. 

PMID- 24325915
TI  - Genome-wide association study identifies 25 known breast cancer susceptibility
      loci as risk factors for triple-negative breast cancer.
AB  - Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer
      associated with a unique set of epidemiologic and genetic risk factors. We
      conducted a two-stage genome-wide association study of TN breast cancer (stage 1:
      1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify
      loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci
      showed genome-wide significant associations (P < 5 * 10(-) (8)) in stage 1 and 2
      combined. Results also suggested a substantial enrichment of significantly
      associated variants among the single nucleotide polymorphisms (SNPs) analyzed in
      stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also
      associated with risk of TN breast cancer (P < 0.05). Associations with TN breast
      cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT
      rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN
      breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1,
      2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24,
      BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously
      reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 * 10(-) (4)]
      and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 * 10(-) (9)) were associated with TN
      breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known
      breast cancer risk variants showed a 4-fold difference in risk between the
      highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P
      = 4.8 * 10(-) (69)). This translates to an absolute risk for TN breast cancer
      ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN
      breast cancer risk prediction. 

PMID- 24325917
TI  - Response to Szolcsanyi.

PMID- 24325919
TI  - Central ventilatory and cardiovascular actions of serotonin in trout.
AB  - This study was undertaken to investigate the central actions of 5-HT on
      ventilatory and cardiovascular variables in the unanesthetized trout. Compared to
      vehicle, intracerebroventricular injection (ICV) of 5-HT elevated the total
      ventilation. This elevation was due to its stimulatory action on ventilatory
      amplitude. Moreover, 5-HT produced a dose-dependent increase in mean dorsal
      aortic blood pressure (PDA) without change in heart rate (fH). Methysergide, a 5
      HT1/5-HT2 receptor antagonist, reduced the hyperventilatory and hypertensive
      actions of 5-HT. 8-OH-2-(di-n-propylamino) tetralin, a 5-HT1A receptor agonist,
      increased PDA while alpha-methyl-5-HT, a 5-HT2 receptor agonist, elevated all
      ventilatory variables and increased PDA without changing fH. Intra-arterial
      injection of 5-HT was without effect on ventilation, but 5-HT initially produced
      hypotension followed by hypertension. These changes were accompanied by
      tachycardia. It remains to be determined whether endogenous 5-HT within the brain
      of trout may act as a potent neuroregulator causing stimulatory effects on cardio
      ventilatory functions. In the periphery, 5-HT may act as local modulator involved
      in vasoregulatory mechanisms. 

PMID- 24325920
TI  - Effect of different concentrations of papain gel on orthodontic bracket bonding.
AB  - BACKGROUND: The objective of this study was to verify the hypothesis that enamel
      deproteinization with papain gel at concentrations of 2%, 4%, 6%, 8%, and 10%
      increases shear bond strength as concentration increases. METHODS: A total of 180
      bovine mandibular permanent incisors were used, divided into six groups (n=30),
      and denominated as follows: group 1 is the control group (CG) in which brackets
      are bonded with resin-modified glass ionomer cement (RMGIC) according to the
      manufacturer's recommendations and groups 2, 3, 4, 5, and 6 have brackets bonded
      with RMGIC after enamel deproteinization with papain gel at concentrations of 2%,
      4%, 6%, 8%, and 10%, respectively. After bonding, teeth were immersed in
      artificial saliva and kept at a temperature of 37 degrees C for 24 h. Mechanical
      tests were then performed in a universal mechanical test machine EMIC DL 5000
      (Sao Jose dos Pinhais, Brazil). Values obtained were submitted to analysis of
      variance and then to Tukey's test (p<0.05). RESULTS: The results demonstrated
      that groups 5 and 6 showed the highest shear bond strength, differing
      statistically from the other groups (p<0.05). CG with no papain gel used showed
      the lowest value and in turn showed no differences for groups 2, 3, and 4. As
      regards adhesive remnant index, CG showed statistical differences from the
      others. Groups 2, 3, 4, 5, and 6, in which papain gel was used, presented no
      statistical differences among them (p>0.05). CONCLUSIONS: It was concluded that
      enamel deproteinization with 8% and 10% papain gel increases shear bond strength
      of orthodontic brackets bonded with RMGIC.

PMID- 24325918
TI  - Amygdala FAAH and anandamide: mediating protection and recovery from stress.
AB  - A long-standing literature linking endocannabinoids (ECBs) to stress, fear, and
      anxiety has led to growing interest in developing novel anxiolytics targeting the
      ECB system. Following rapid on-demand biosynthesis and degradation upon neuronal
      activation, the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively
      degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH).
      Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA
      and increase neuronal excitability in a key anxiety-mediating region--the
      basolateral amygdala (BLA). Gene deletion or pharmacological inhibition of FAAH
      prevents stress-induced reductions in AEA and associated increases in BLA
      dendritic hypertrophy and anxiety-like behavior. Additionally, inhibition of FAAH
      facilitates long-term fear extinction and rescues deficient fear extinction in
      rodent models by enhancing AEA-CB1 (cannabinoid type 1) receptor signaling and
      synaptic plasticity in the BLA. These preclinical findings propose restoring
      deficient BLA AEA levels by pharmacologically inhibiting FAAH as a mechanism to
      therapeutically mitigate the effects of traumatic stress.

PMID- 24325922
TI  - Imaging features of carcinoid heart disease.
AB  - This article reviews the basic and clinical features of heart disease associated
      with carcinoid syndrome, with an emphasis on its principal imaging modalities.

PMID- 24325921
TI  - Pseudo-subarachnoid hemorrhage: a potential imaging pitfall.

PMID- 24325923
TI  - Renal transplant complications: diagnostic and therapeutic role of radiology.
AB  - Kidney was the first and is the most frequently transplanted organ. Despite
      improved surgical techniques and transplantation technology, complications do
      occur and, if left untreated, may lead to catastrophic consequences. Renal
      transplantation complications may be vascular (eg, renal artery and vein stenosis
      and thrombosis, arteriovenous fistula, and pseudoaneurysms); urologic (eg,
      urinary obstruction and leak, and peritransplantation fluid collections,
      including hematoma, seroma, lymphocele, and abscess formation); and nephrogenic,
      including acute tubular necrosis, graft rejection, chronic allograft nephropathy,
      and neoplasm. Early diagnosis and treatment of these complications are paramount
      to prevent graft failure and other significant morbidities to the patients.
      Radiology plays a pivotal role in the diagnosis and treatment of these
      complications, with minimally invasive percutaneous techniques. In this article,
      we reviewed renal transplantation anatomy, a wide range of complications that may
      occur after renal transplantation surgery, typical imaging appearances of the
      complications on varies imaging modalities, and percutaneous interventional
      techniques that are used in their treatment.

PMID- 24325924
TI  - Comparison of the spectrum of radiologic and clinical manifestations of pulmonary
      disease caused by Mycobacterium avium complex and Mycobacterium xenopi.
AB  - AIM: Mycobacterium xenopi is described with upper lobe cavitation
      ("fibrocavitary" pattern), whereas the Mycobacterium avium complex (MAC) is
      described with bronchiectasis and centrilobular nodules ("nodular
      bronchiectasis"). We retrospectively described and compared computed tomography
      (CT) chest manifestations of disease caused by MAC and M xenopi. MATERIALS AND
      METHODS: We reviewed patients who had either MAC or M xenopi lung disease and who
      had CTs between January 2002 and December 2003. Clinical data were recorded, and
      the patterns on chest CTs were categorized as "fibrocavitary," "nodular
      bronchiectatic," and "unclassified." RESULTS: There were 74 patients; 50 with MAC
      and 24 with M xenopi. The patients with MAC were older (mean 69 vs 58 years; P =
      .007). Patients with M xenopi more often had emphysema (50% vs 20%; P = .02),
      cavities (46% vs 16%; P = .01), and nodules <=5 mm (88% vs 58%; P = .02). M
      xenopi cases more commonly had a fibrocavitary radiologic pattern (33% vs 18%),
      with no statistically significant difference (P = .24). MAC was more often
      associated with a nodular bronchiectatic pattern (68% MAC vs 4% M xenopi; P <
      .0001). Sixty-three percent of patients with M xenopi had a pattern that was
      predominantly randomly distributed nodules (11/15 [73%]) or consolidation and/or
      ground-glass opacities (4/15 [27%]). CONCLUSION: Compared with MAC, patients with
      M xenopi infection develop more cavities and more nodules, and they less often
      have a predominant nodular bronchiectatic pattern. Although a predominantly
      cavitary pattern appears to be more common with M xenopi, the majority of
      patients with M xenopi had CT patterns of random nodules or consolidation and/or
      ground-glass opacities rather than classically described findings.

PMID- 24325925
TI  - Within- and between-child variation in repeated urinary pesticide metabolite
      measurements over a 1-year period.
AB  - BACKGROUND: Children are exposed to pesticides from many sources and routes,
      including dietary and incidental ingestion, dermal absorption, and inhalation.
      Linking health outcomes to these exposures using urinary metabolites requires
      understanding temporal variability within subjects to avoid exposure
      misclassification. OBJECTIVES: We characterized the within- and between-child
      variability of urinary organophosphorus and pyrethroid metabolites in 23
      participants of the Children's Pesticide Exposure Study-Washington over 1 year
      and examined the ability of one to four spot urine samples to categorize mean
      exposures. METHODS: Each child provided urine samples twice daily over 7- to 16
      day sessions in four seasons in 2003 and 2004. Samples were analyzed for five
      pyrethroid and five organophosphorus (OP) metabolites. After adjusting for
      specific gravity, we used a customized maximum likelihood estimation linear mixed
      effects model that accounted for values below the limit of detection to calculate
      intraclass correlation coefficients (ICC) and conducted surrogate category
      analyses. RESULTS: Within-child variability was 2-11 times greater than between
      child variability. When restricted to samples collected during a single season,
      ICCs were higher in the fall, winter, and spring than in summer for OPs, and
      higher in summer and winter for pyrethroids, indicating an increase in between
      person variability relative to within-person variability during these seasons.
      Surrogate category analyses demonstrated that a single spot urine sample did not
      categorize metabolite concentrations well, and that four or more samples would be
      needed to categorize children into quartiles consistently. CONCLUSIONS: Urinary
      biomarkers of these short half-life pesticides exhibited substantial within
      person variability in children observed over four seasons. Researchers
      investigating pesticides and health outcomes in children may need repeated
      biomarker measurements to derive accurate estimates of exposure and relative
      risks.

PMID- 24325926
TI  - Incomplete restoration of Mycobacterium tuberculosis-specific-CD4 T cell
      responses despite antiretroviral therapy.
AB  - OBJECTIVES: Despite antiretroviral therapy (ART), HIV-infected persons have
      increased risk of active tuberculosis (TB). PPD and combined ESAT-6 and CFP-10
      specific-CD4 (EC-Sp-CD4) responses were examined over 96 weeks. METHODS: HIV
      infected, ART-naive Thai adults with CD4 T cell count <=350 cells/MUL starting
      ART were assessed at baseline, wk4, 8, 12, 24, 48 and 96. PPD and EC-Sp-CD4 T
      cells were detected by CD25/CD134 co-expression after stimulation with antigens.
      RESULTS: Fifty subjects were enrolled, 39 were male, median age 32 yrs, median
      baseline CD4 T cell count 186 cells/MUL and plasma HIV-viral-load 4.9log10
      copies/mL. Seventeen were TB-sensitised. At baseline, 25 had positive PPD and 15
      had positive EC-Sp-CD4 response. CD4 T cell count <100 cells/MUL was less (P =
      0.005) and TB-sensitisation was more likely (P = 0.013) to be associated with
      positive baseline PPD-Sp-CD4 response. At wk4, the number of subjects with
      positive PPD-Sp-CD4 response rose to 35 (P = 0.021). Mean PPD-Sp-CD4 T cells
      increased at wk4 (P = 0.017) in patients not classified as TB-sensitised. The
      number of subjects with positive EC-Sp-CD4 response did not change significantly
      post ART. In TB-sensitised patients, mean EC-Sp-CD4 T cells declined to below
      baseline from wk12 (P = 0.010) onwards. EC-Sp-CD4 responses were undetectable in
      3 out of 17 TB-sensitised patients. CONCLUSIONS: Restoration of responses to TB
      antigens was incomplete and inconsistent under the employed experimental
      conditions and may account for persistent increased risk of TB despite ART.

PMID- 24325927
TI  - An approach for assessing effectiveness of a vaccination campaign against
      pertussis among young adults: the example of the French armed forces (2007-2012).

PMID- 24325928
TI  - Characterization and spinal fusion effect of rabbit mesenchymal stem cells.
AB  - BACKGROUND: The surface markers of mesenchymal stem cells (MSCs) of rabbits have
      been reported only sporadically. However, interest in the spinal fusion effect of
      MSCs has risen recently. The purpose of this research was to study the surface
      markers and spinal fusion effect of rabbit MSCs. RESULTS: Of our rabbit MSCs, 2%
      expressed CD14, CD29, and CD45, 1% expressed CD90 and 97% expressed CD44. These
      results implied the MSCs were negative for CD14, CD29, CD45, and CD90, but
      positive for CD44. The surgical results showed that satisfactory fusion occurred
      in 10 rabbits (83%) in the study group and unsatisfactory fusion in 2 (17%). In
      the control group, satisfactory fusion was found in 3 rabbits (25%) and
      unsatisfactory fusion in 9 (75%). Statistical analysis showed the study group had
      significantly better spinal fusion results than the control group. CONCLUSIONS:
      The surface markers of human and rabbit MSCs are not exactly the same. Rabbit
      MSCs do not have positive reactivity for CD29 and CD90, which are invariably
      present on human MSCs. The allogeneic undifferentiated rabbit MSCs were able to
      promote spinal fusion and did not induce an adverse immune response.

PMID- 24325930
TI  - Human cadaveric specimen study of the prostatic arterial anatomy: implications
      for arterial embolization.
AB  - PURPOSE: To describe and illustrate the prostatic arterial anatomy from human
      cadaveric specimens, highlighting implications for prostatic arterial
      embolization. MATERIALS AND METHODS: Dissection of 18 male pelves from white
      adults 35-68 years old was performed in the anatomy laboratory. Arterial branches
      were identified according to standard dissection technique using a 20-diopter
      magnifying lens for the prostatic sector. The branches were colored with red
      acrylic paint to enhance contrast and improve visualization. RESULTS: Two main
      arterial pedicles to the prostate from each hemipelvis were identified in all
      cadaveric specimens: the superior and inferior prostatic pedicles. The superior
      prostatic pedicle provides the main arterial supply of the gland and provides
      branches to both the inferior bladder and the ejaculatory system. The inferior
      prostatic pedicle distributes as a plexus in the prostatic apex and anastomoses
      with the superior pedicle. This pattern of prostatic arterial distribution was
      constant in all cadaveric specimens. In contrast, the origin of the superior
      prostatic pedicle was variable from different sources of the internal iliac
      artery. CONCLUSIONS: The description and illustration of the prostatic arterial
      anatomy, as demonstrated by this cadaveric study, may provide useful information
      and guidance for prostatic arterial embolization.

PMID- 24325929
TI  - Position statement on percutaneous vertebral augmentation: a consensus statement
      developed by the Society of Interventional Radiology (SIR), American Association
      of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS),
      American College of Radiology (ACR), American Society of Neuroradiology (ASNR),
      American Society of Spine Radiology (ASSR), Canadian Interventional Radiology
      Association (CIRA), and the Society of NeuroInterventional Surgery (SNIS).

PMID- 24325932
TI  - Global Mittag-Leffler stability and synchronization of memristor-based fractional
      order neural networks.
AB  - The present paper introduces memristor-based fractional-order neural networks.
      The conditions on the global Mittag-Leffler stability and synchronization are
      established by using Lyapunov method for these networks. The analysis in the
      paper employs results from the theory of fractional-order differential equations
      with discontinuous right-hand sides. The obtained results extend and improve some
      previous works on conventional memristor-based recurrent neural networks. 

PMID- 24325931
TI  - Roll-in experience from the Cardiovascular Outcomes with Renal Atherosclerotic
      Lesions (CORAL) study.
AB  - PURPOSE: To describe the experience and results from the roll-in phase of the
      Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study.
      MATERIALS AND METHODS: The CORAL roll-in database was used to describe the
      baseline characteristics of the patients in the roll-in cohort, all of whom
      underwent renal artery stent placement; to evaluate CORAL site performance; to
      compare estimates of lesion (stenosis) severity made by site interventionalists
      with the central CORAL angiographic core laboratory readings; and to report
      outcomes after renal artery stent placement. During the roll-in phase, 239
      patients (mean age, 70.2 y +/- 9.0; 49% male) underwent renal artery stent
      procedures. Angiographic core laboratory analysis of renal arteriograms was done,
      and participants were followed at 1 month and 9 months. RESULTS: Major
      angiographic complications were identified in 28 (13%) subjects. Kidney function
      remained unchanged at the short (2-4 weeks) follow-up interval. Improvement in
      systolic blood pressure with use of distal embolic protection devices (n = 161)
      did not show any clinical benefit over nonuse of such devices (n = 78) in this
      small series. At 9 months, there were significantly more endpoints reported by
      site in subjects with bilateral renal artery stenosis (P = .01) and prior history
      of stroke (P = .03). CONCLUSIONS: In the roll-in phase of the CORAL study, a
      significant number of angiographic complications were identified. No effect was
      seen on estimated glomerular filtration rate after renal artery stent placement,
      but systolic blood pressure decreased significantly.

PMID- 24325933
TI  - The novel use of three-dimensional surface models to quantify and visualise the
      immediate changes of the mid-facial skeleton following rapid maxillary expansion.
AB  - BACKGROUND: The transverse skeletal effects of rapid maxillary expansion (RME)
      have previously been assessed using cone-beam CT (CBCT). However, to date the
      majority of studies assess the changes based on two-dimensional slice images,
      which under utilises the three-dimensional (3D) data captured. This study
      optimizes the volumetric CBCT data by generating 3D rendered surface models to
      quantity and visualize the immediate 3D changes of the mid-facial bone surfaces
      following RME. METHODS: The sample consisted of 14 patients who required RME
      prior to fixed appliances. Pre-treatment (T0) and immediate post expansion (T1)
      CBCT images were taken. Following superimposition the mid face was divided into
      six anatomical regions. A one-sample t-test was used to determine if the
      differences between the two surfaces were significantly >=0.5 mm. FINDINGS: All
      regions showed a change following RME >= 0.5 mm. The maxillary and nasal bones
      showed 2.3 mm and 2.4 mm expansion respectively, followed by the zygomatic bones
      (1.4 mm), 2 cases showing asymmetric expansion. CONCLUSIONS: The use of 3D
      surface rendered models allows quantification and visualisation of 3D changes in
      the mid-facial skeleton at anatomical sites distant of RME activation. Following
      activation there can be a pan mid-facial expansion, including not only the
      maxilla but also the nasal lateral bones and zygomas. The response was highly
      variable and asymmetric expansion can occur.

PMID- 24325934
TI  - Surgeons' work engagement: influencing factors and relations to job and life
      satisfaction.
AB  - BACKGROUND: Work engagement has become a topic of great interest in recent years.
      However, clinicians' work engagement has rarely been studied and relatively
      little is known about its predictors and consequences. Therefore the objective of
      this cross-sectional questionnaire study was to test a model of possible
      institutional and personal predictors and significant relations to job and life
      satisfaction. METHODS: 123 clinicians specializing in Surgery Medicine
      participated in the study. Self-administered questionnaires, including the
      Copenhagen Psychosocial Questionnaire, the Utrecht Work Engagement Scale, the
      Brief Resilient Coping Scale and the Questionnaire for Self-efficacy, Optimism
      and Pessimism, were administered. Bivariate analyses and a stepwise regression
      analysis were performed. RESULTS: The whole sample of surgeons rated work
      engagement with a high mean of M = 4.38; SD = .91. Job satisfaction and perceived
      quality of life have been rated with moderate scores. The results show that job
      resources have a greater impact on surgeons' work engagement than their job
      demands. Significant correlations between surgeons' work engagement, their job
      satisfaction and quality of life were found. Moreover, work engagement mediated
      the relation between institutional factors and surgeons' job satisfaction.
      CONCLUSION: Our research suggests that strengthening surgeons' work engagement
      will contribute to a more sustainable workplace, in terms of both individual and
      hospital performance. Therefore, increasing work engagement among surgeons should
      be of concern for supervisors and hospital managers. Future research should focus
      on further predictors that may have an influence on health professionals' work
      engagement. Another field for future research is to study potential effects of
      interventions on work engagement.

PMID- 24325935
TI  - Occlus-o-Guide(r) versus Andresen activator appliance: neuromuscular evaluation.
AB  - BACKGROUND: The aim of the present study was to assess the muscular variations at
      the electromyography (EMG) level for the anterior temporalis muscles and masseter
      muscles during treatment with Occlus-o-Guide(r) and Andresen activator
      appliances. METHODS: Eighty-two patients (35 males and 47 females) aged between 8
      and 12 years (mean age, 10.5+/-0.8 years) participated in the study. Fifty
      patients underwent treatment with an Occlus-o-Guide(r) and 32 patients with an
      Andresen activator. All patients underwent EMG examination using a Freely EMG (De
      Gotzen, Legnano, Italy) and surface bipolar electrodes when the appliances were
      worn for the first time (T0), and after 6 months (T1) and after 12 months (T2) of
      appliance use. RESULTS: Statistical analysis showed that both at T0 and T2, the
      percent overlapping coefficient (POC) of the anterior temporalis muscles was not
      statistically different between the appliance groups. At T0, the POC of the
      masseter muscles was significantly lower for the Andresen appliance as compared
      to the Occlus-o-Guide(r) (p=0.02), while at T2 this significance was lost.
      CONCLUSIONS: At insertion of an appliance, all patients show neuromuscular
      balance that does not correspond to orthognathic occlusion. Both appliances work
      by creating muscular imbalance. With the appliances in situ, EMG responses were
      generally analogous for the Occlus-o-Guide(r) and the Andresen activator;
      however, the imbalance was greater and the recovery of the orthological muscular
      balance was slower in patients under treatment with the Andresen activator as
      compared to those with the Occlus-o-Guide(r).

PMID- 24325936
TI  - Intrathecal leptin inhibits expression of the P2X2/3 receptors and alleviates
      neuropathic pain induced by chronic constriction sciatic nerve injury.
AB  - BACKGROUND: Leptin, an adipocytokine produced mainly by white adipose tissue, has
      a broad role in the regulation of neuronal functions. Accumulating evidence has
      revealed that leptin plays an important role in influencing neuropathic pain,
      shown recently by the finding that chronic administration of leptin induced
      thermal hyperalgesia and mechanical allodynia in naive rats. Chronic constriction
      sciatic nerve injury (CCI) is a well characterized model used for studying
      neuropathic pain. The present study was designed to investigate whether leptin
      plays a role in neuropathic pain in rats induced by CCI by examining particular
      pain behaviors. RESULTS: After sciatic nerve injury in rats, endogenous levels of
      leptin and leptin receptor (OB-Rb) were increased in a time dependent manner
      within the ipsilateral dorsal root ganglion (DRG). Intrathecal administration of
      leptin once daily for 6 days, beginning 7 days after CCI, alleviated neuropathic
      pain and decreased the expression of IL-6, TNFalpha, and the P2X2 and P2X3
      receptors. Attenuation of endogenous OB-Rb in the DRG by intrathecal
      administration of OB-Rb antisense oligonucleotides did not change thermal
      hyperalgesia or mechanical allodynia induced by CCI. CONCLUSIONS: Our findings
      suggest that exogenous leptin can alleviate the chronic neuropathic pain caused
      by CCI. The leptin effect may be mediated by attenuated expression of IL-6,
      TNFalpha, and the P2X2 and P2X3 receptors in the DRG of CCI rats.

PMID- 24325937
TI  - Impact of sertraline salt form on the oxidative stability in powder blends.
AB  - Oxidation of active pharmaceutical ingredients is a common chemical degradation
      process occurring in solid dosage forms. The aim of this study was to investigate
      the tendency of various sertraline salts to oxidize in powder blends containing a
      basic additive. A different extent of conversion of each salt to the free base
      was observed to occur in the presence of the basic additive, consistent with
      their respective pHmax values. Sertraline was found to undergo oxidation as the
      unioinized form, in both solution and powder blends that incorporated an
      oxidizing agent. In contrast, the ionized form of sertraline remained stable in
      both cases. Three sertraline salts undergoing a significant extent of conversion
      from salt to free form in the presence of tribasic sodium phosphate were found to
      oxidize extensively while sertraline benzoate which had a considerably lower
      extent of free base formation was more resistant to oxidation. The oxidative
      degradants were produced through oxidation at the amine functional group of
      sertraline which is where sertraline is ionized as the salt form. The link
      between oxidation tendency and the ionization state of sertraline in powder
      mixtures has thus been demonstrated in this study. 

PMID- 24325938
TI  - Isothermal calorimetry: a predictive tool to model drug-propellant interactions
      in pressurized metered dose systems.
AB  - The purpose of this work was to evaluate gas perfusion isothermal calorimetry
      (ITC) as a method to characterize the physicochemical changes of active
      pharmaceutical ingredients (APIs) intended to be formulated in pressurized
      metered dose inhalers (pMDIs) after exposure to a model propellant. Spray dried
      samples of beclomethasone dipropionate (BDP) and salbutamol sulphate (SS) were
      exposed to controlled quantities of 2H,3H-decafluoropentane (HPFP) to determine
      whether ITC could be used as a suitable analytical method for gathering data on
      the behavioural properties of the powders in real time. The crystallization
      kinetics of BDP and the physiochemical properties of SS were successfully
      characterized using ITC and supported by a variety of other analytical
      techniques. Correlations between real and model propellant systems were also
      established using hydrofluoroalkane (HFA-227) propellant. In summary, ITC was
      found to be suitable for gathering data on the crystallization kinetics of BDP
      and SS. In a wider context, this work will have implications on the use of ITC
      for stability testing of APIs in HFA-based pMDIs. 

PMID- 24325939
TI  - Accuracy of a screening instrument to identify potential child abuse in emergency
      departments.
AB  - Although screening for child abuse at emergency departments (EDs) increases the
      detection rate of potential child abuse, an accurate instrument is lacking. This
      study was designed to measure the accuracy of a screening instrument for
      detection of potential child abuse used in EDs. In a prospective cohort study at
      three Dutch EDs, a 6-item screening instrument for child abuse, Escape, was
      completed for each child visiting the ED. The data from the completed Escape
      instrument was used to calculate sensitivity, specificity, and the
      positive/negative predictive value per item. The clinical notes and conclusions
      of the screen instruments of all potentially abused children reported to the
      hospitals' Child Abuse Teams were collected and reviewed by an expert panel. A
      logistic regression model was used to evaluate the predictors of potential abuse.
      Completed Escape instruments were available for 18,275 ED visits. Forty-four of
      the 420 children with a positive screening result, and 11 of the 17,855 children
      with a negative result were identified as potentially abused. Sensitivity of the
      Escape instrument was 0.80 and specificity was 0.98. Univariate logistic
      regression showed that potentially abused children were significantly more likely
      to have had an aberrant answer to at least one of the items, OR=189.8, 95% CI
      [97.3, 370.4]. Most of the children at high risk for child abuse were detected
      through screening. The Escape instrument is a useful tool for ED staff to support
      the identification of those at high risk for child abuse. 

PMID- 24325941
TI  - A new device (FAQ.FIX(r)) for orthodontic bracket placement in straight wire
      technique.
AB  - BACKGROUND: In straight wire preadjusted appliances, all the information required
      to position the teeth in three planes is included in the brackets placed at the
      midpoint of the facial axis of the clinical crown, defined by facial axis point
      (FA). Central to this technique is the bracket placement.Preadjusted orthodontic
      appliances cannot get the right tooth position with a straight wire because of
      the inaccuracy of bracket placement. Horizontal, axis, vertical, and base are the
      most common bracket placement errors.The aim of this paper was to describe a
      bracket positioner to fix the brackets accurately (Q) on FA point (FAQ.FIX(r)) in
      direct or indirect bonding. METHODS: After the development of a prototype, a
      FAQ.FIX(r) along with a Bracket Placement Clinical Chart was developed and thus
      described. RESULTS: FAQ.FIX(r) along with the Bracket Placement Clinical Chart
      may facilitate the accuracy in bracket placement on FA point avoiding the most
      common bracket placement errors regardless the operator skill, even in particular
      or difficult case. CONCLUSIONS: FAQ.FIX(r)may represent a significant improvement
      in the bracket placement compared to the bracket eye and the traditional gauges
      positioning. Further studies will be needed to verify the clinical efficacy.

PMID- 24325940
TI  - Child abuse and neglect and intimate partner violence victimization and
      perpetration: a prospective investigation.
AB  - This paper describes the extent to which abused and neglected children report
      intimate partner violence (IPV) victimization and perpetration when followed up
      into middle adulthood. Using data from a prospective cohort design study,
      children (ages 0-11) with documented histories of physical and sexual abuse
      and/or neglect (n=497) were matched with children without such histories (n=395)
      and assessed in adulthood (Mage=39.5). Prevalence, number, and variety of four
      types of IPV (psychological abuse, physical violence, sexual violence, and
      injury) were measured. Over 80% of both groups - childhood abuse and neglect
      (CAN) and controls - reported some form of IPV victimization during the past year
      (most commonly psychological abuse) and about 75% of both groups reported
      perpetration of IPV toward their partner. Controlling for age, sex, and race,
      overall CAN [adjusted odds ratio (AOR)=1.60, 95% CI [1.03, 2.49]], physical abuse
      (AOR=2.52, 95% CI [1.17, 5.40]), and neglect (AOR=1.64, 95% CI [1.04, 2.59])
      predicted increased risk for being victimized by a partner via physical injury.
      CAN and neglect also predicted being victimized by a greater number and variety
      of IPV acts. CAN and control groups did not differ in reports of perpetration of
      IPV, although neglect predicted greater likelihood of perpetrating physical
      injury to a partner, compared to controls. Abused/neglected females were more
      likely to report being injured by their partner, whereas maltreated males did
      not. This study found that child maltreatment increases risk for the most serious
      form of IPV involving physical injury. Increased attention should be paid to IPV
      (victimization and perpetration) in individuals with histories of neglect. 

PMID- 24325942
TI  - Preoperative exercise therapy for elective major abdominal surgery: a systematic
      review.
AB  - OBJECTIVES: The impact of postoperative complications after Major Abdominal
      Surgery (MAS) is substantial, especially when socio-economical aspects are taken
      into account. This systematic review focuses on the effects of preoperative
      exercise therapy (PEXT) on physical fitness prior to MAS, length of hospital
      admission and postoperative complications in patients eligible for MAS, and on
      what is known about the most effective kind of exercise regime. METHODS: A
      systematic search identified randomised controlled trials on exercise therapy and
      pulmonary physiotherapy prior to MAS. The methodological quality of the included
      studies was rated using the 'Delphi List For Quality Assessment of Randomised
      Clinical Trials'. The level of agreement between the two reviewers was estimated
      with Cohen's kappa. RESULTS: A total of 6 studies were included, whose
      methodological quality ranged from moderate to good. Cohen's kappa was 0.90.
      Three studies reported on improving physical fitness prior to MAS with the aid of
      PEXT. Two studies reported on the effect of training on postoperative
      complications, showing contradictory results. Three studies focused on the effect
      of preoperative chest physiotherapy on postoperative lung function parameters
      after MAS. While the effects seem positive, the optimal training regime is still
      unclear. CONCLUSION: Preoperative exercise therapy might be effective in
      improving the physical fitness of patients prior to major abdominal surgery, and
      preoperative chest physiotherapy seems effective in reducing pulmonary
      complications. However consensus on training method is lacking. Future research
      should focus on the method and effect of PEXT before high-risk surgical
      procedures.

PMID- 24325943
TI  - Ecotoxicology inside the gut: impact of heavy metals on the mouse microbiome.
AB  - BACKGROUND: The gut microbiota is critical for intestinal homeostasis. Recent
      studies have revealed the links between different types of dysbiosis and diseases
      inside and outside the intestine. Environmental exposure to pollutants (such as
      heavy metals) can also impair various physiological functions for good health.
      Here, we studied the impact of up to 8 weeks of oral lead and cadmium ingestion
      on the composition of the murine intestinal microbiome. RESULTS: Pyrosequencing
      of 16S RNA sequences revealed minor but specific changes in bacterial commensal
      communities (at both family and genus levels) following oral exposure to the
      heavy metals, with notably low numbers of Lachnospiraceae and high numbers levels
      of Lactobacillaceae and Erysipelotrichaceacae (mainly due to changes in
      Turicibacter spp), relative to control animals. CONCLUSIONS: Non-absorbed heavy
      metals have a direct impact on the gut microbiota. In turn, this may impact the
      alimentary tract and overall gut homeostasis. Our results may enable more
      accurate assessment of the risk of intestinal disease associated with heavy metal
      ingestion.

PMID- 24325944
TI  - Electrical conductivity measurements of urine as a new simplified method to
      evaluate the diuretic activity of medicinal plants.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Diuretic plants are widely used in traditional
      medicine in many countries. However, many of these species have not been
      subjected to experimental studies to confirm that property. In this paper, a
      simple new method is proposed to evaluate the diuretic activity of plants. We
      define a new index that takes into account only the volume of urinary excretion
      and total ion concentration excreted obtained by specific electrical conductivity
      measurements. MATERIALS AND METHODS: Urine was collected in a graduate cylinder
      during the 8h after Artemisia thuscula (AT), Withania aristata (WA), Smilax
      canariensis (SC) and HCTZ oral administration to laboratory mice. To obtain the
      new index Diuretic Power (DP), we measured the specific electrical conductivity
      (kappa) of the fresh urine samples. We calculated the concentration of a NaCl (or
      KCl) aqueous solution that has the same specific electrical conductivity as the
      urine sample. We multiplied this concentration by the corresponding urinary
      excretion volume, thus obtaining the total mEq. of electrolyte excreted "as if
      all were NaCl (or KCl)". Finally, we divided these mEq. by those corresponding to
      the control to obtain the DP value. RESULTS: HCTZ showed a 40% increase in DP,
      with respect to the control group, independently of the doses used, and the
      studied plants produced an increase between 7 and 28%. DP values were compared
      with other common indexes, DI and SIi, showing that the variation sequence of the
      three indexes was the same for HCTZ, WA and SC. CONCLUSIONS: A new and easy
      index, that we called diuretic power (DP), for estimating the diuretic activity
      of drugs or plants is proposed. It allows us to highlight diuretic effect with
      respect to a control value of a large amount of drugs or plants that had not been
      previously experimentally studied.

PMID- 24325945
TI  - Candida albicans lumbar spondylodiscitis in an intravenous drug user: a case
      report.
AB  - BACKGROUND: Spondylodiscitis leads to debility, and few data exist on Candida
      spondylodiscitis in patients with intravenous drug use. CASE PRESENTATION: We
      present a case of Candida albicans lumbar spondylodiscitis in a patient with
      intravenous drug use. This patient was treated with surgical debridement and 9
      months of fluconazole therapy, and the neurological deficits resolved completely.
      The infection did not recur clinically or radiologically during 9 months of
      follow-up. CONCLUSION: Although Candida albicans lumbar spondylodiscitis is rare,
      Candida should be suspected as a causative pathogen in patients with intravenous
      drug use except for Staphylococcus aureus, Pseudomonas aeruginosa, and
      Mycobacterium tuberculosis. As soon as Candida albicans lumbar spondylodiscitis
      is suspected, magnetic resonance imaging and percutaneous biopsy should be
      performed. Surgical intervention combined with treatment with antifungal
      medications can successfully eradicate the infection and resolve the neurological
      deficits.

PMID- 24325946
TI  - Re: Arakeri G, Brennan PA. Oral submucous fibrosis: an overview of the aetiology,
      pathogenesis, classification, and principles of management. Br J Oral Maxillofac
      Surg 51 (2013) 587-593.

PMID- 24325947
TI  - Intraoral adenoid cystic carcinoma: is the presence of perineural invasion
      associated with the size of the primary tumour, local extension, surgical
      margins, distant metastases, and outcome?
AB  - Adenoid cystic carcinoma is the most common malignancy of the minor salivary
      glands, and its biological behaviour is characterised by slow and indolent
      growth; rare involvement of regional lymph nodes; a high propensity for
      perineural invasion; multiple or delayed recurrences, or both; and a high
      incidence of distant metastases. Our aim was to find out the relation between the
      presence of perineural invasion and these factors. Between 1 January 1984 and 1
      May 2008, 26 cases of adenoid cystic carcinoma of the intraoral salivary glands,
      which had initially been treated surgically, were reviewed retrospectively. The
      most common site was the palate, and perineural invasion was reported in 13 of
      the 26 resected specimens. There was no significant association between it and
      the size of the primary tumour (OR=1.0; p=1.00), invasion of the surgical margins
      (OR=2.08; p=0.4), the presence of distant metastases (OR=3.43; p=0.197), or local
      control (p=0.76). It was exclusively present in patients with local extension,
      and was significantly associated with outcome (p=0.04). Resection with clear
      margins is the gold standard of care for patients with intraoral adenoid cystic
      carcinoma, and the role of adjuvant irradiation remains controversial. Given its
      paradoxical and complex biological behaviour, large studies with long term follow
      up are needed to define the clinicopathological and immunohistochemical variables
      associated with outcome, as well as the optimal treatment.

PMID- 24325948
TI  - Survival outcomes in breast cancer patients with low estrogen/progesterone
      receptor expression.
AB  - INTRODUCTION: The prognostic value of low estrogen and progesterone receptors
      expression (ER/PgR 1%-10%) in early breast cancer patients is still unclear.
      PATIENTS AND METHODS: We retrospectively analyzed 1424 consecutive patients with
      HER2/neu-negative and low endocrine receptors expression early breast cancer,
      submitted to surgery at the European Institute of Oncology between January 1995
      and December 2009. Patients were classified according to the percentage of ER/PgR
      expression using immunohistochemistry. Group 1 with ER/PgR < 1%, and group 2 with
      ER/PgR 1% to 10%. RESULTS: Group 1 (ER/PgR < 1%) included 1300 patients, and
      group 2 (ER/PgR 1%-10%) 124 patients. Median follow-up time was 74 months (range,
      3-192 months). The 5-year disease-free survival (DFS) rate was 74% (95%
      confidence interval [CI], 72%-77%) for group 1, and 79% (95% CI, 70%-86%) for
      group 2 (P = .16). The 5-year overall survival (OS) rate was 86% (95% CI, 84%
      88%) in group 1 and 90% (95% CI, 83%-95%) in group 2 (P = .13). In patients
      without lymph node involvement, the 5-year OS rate was 92% (95% CI, 89.5%-93.6%)
      for group 1 and 98% (95% CI, 90.2%-99.8%) for group 2 (P = .061). One hundred ten
      patients received endocrine therapy with no significant effect on DFS (P = .36)
      and OS (P = .30). CONCLUSION: The ER/PgR 1%-10% group had a slight, but not
      statistically significant, better prognosis than the ER/PgR <1% group. Further
      studies are needed to identify the appropriate clinical approach in this subset
      of patients with low ER/PgR expression (ER/PgR 1%-10%), HER2-negative early
      breast cancer.

PMID- 24325949
TI  - Validation of a real-time quantitative polymerase chain reaction method for the
      quantification of 3 survivin transcripts and evaluation in breast cancer tissues.
AB  - BACKGROUND: Survivin is a novel antiapoptotic gene, which is a member of the
      inhibitor of apoptosis protein (IAP) family. Recently, 3 splice variants of this
      gene were cloned and characterized. This study aimed to validate a sensitive and
      specific method for the detection of survivin variants in breast cancer. METHODS:
      Real-time quantitative polymerase chain reaction (qPCR) was performed on the cDNA
      with a reverse primer specific for each splice variant and a pair of common
      hybridization probes. RESULTS: The expression of wild-type survivin was
      significantly correlated with survivin-2b, survivin-DeltaEx3, and the ratio of
      survivin-DeltaEx3 to wild-type survivin (P < .001). The ratio of survivin-2b to
      wild-type survivin was strongly associated with the ratio of survivin-DeltaEx3 to
      wild-type survivin (P < .001). There was a strong positive association between
      the grade of the tumor and survivin-2b mRNA, survivin-DeltaEx3 mRNA, and the
      ratio of survivin-DeltaEx3 to wild-type survivin mRNA (P < .05). The ratio of
      survivin-2b to wild-type survivin was significantly associated with the presence
      of estrogen receptors (P = .05). CONCLUSION: Our validated data suggest that
      survivin isoforms may be related to clinicopathological features and could be
      used as molecular prognostic tools or as new therapy targets.

PMID- 24325950
TI  - Multicenter experience of nonpegylated liposomal doxorubicin use in the
      management of metastatic breast cancer.
AB  - BACKGROUND: This study aimed to investigate the use of nonpegylated liposomal
      doxorubicin (NPLD) in the management of metastatic breast cancer (MBC) within
      routine UK clinical practice and to assess its efficacy and tolerability.
      PATIENTS AND METHODS: All patients that received NPLD for MBC at 5 institutions
      were identified. Clinicopathologic details, echocardiographic data, and
      toxicities were documented. Response to treatment, outcome, cardiotoxicity, and
      safety were assessed. RESULTS: 63 patients (median age at NPLD therapy, 53.5
      years) who had received NPLD were identified; 18 (29%) were anthracycline-naive,
      and 42 (67%) were anthracycline-pretreated (median cumulative dose of epirubicin,
      450 mg/m(2)). In 3 cases, prior treatment history was not available. NPLD was
      most frequently (16 [25%] of 63 patients) administered as first-line chemotherapy
      (median, third-line; range, 1-9), although it was given later in anthracycline
      pretreated patients (median, fourth-line; range, 1-9). Overall, 14 (29%) of 49
      evaluable patients achieved an objective response, which increased to 10 (71%) of
      14 when NPLD was given first-line (anthracycline-naive, 8 [100%] of 8;
      anthracycline-pretreated, 2 [50%] of 4; adjuvant treatment unknown, 2). Median
      progression-free survival was 7 months (first-line, 18 months, vs. >= second
      line, 6 months; P = .0066), and median overall survival was 10 months (first
      line, 18 months, vs. >= second-line, 10 months; P = .0971). Toxicities tended to
      be grade 1 or 2. Three patients had cardiotoxicity (left ventricular ejection
      fraction < 50% or a fall of >= 10% from baseline), which resolved during
      treatment. CONCLUSION: NPLD was used in both anthracycline-naive patients and
      those with prior exposure. There is evidence of clinical activity in those with
      prior exposure to anthracyclines, with a low incidence of cardiotoxicity.

PMID- 24325951
TI  - Circulating levels of soluble MER in lupus reflect M2c activation of
      monocytes/macrophages, autoantibody specificities and disease activity.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is characterized by impaired
      efferocytosis and aberrant activation of innate immunity. We asked if shedding of
      MER receptor tyrosine kinase (MerTK) and AXL into soluble (s) ectodomains was
      related to immunological and clinical aspects of SLE. METHODS: Levels of sMER and
      sAXL in the plasma of 107 SLE patients and 45 matched controls were measured by
      ELISA. In 40 consecutive SLE patients, we examined potential correlations between
      either sMER or sAXL and plasma levels of sCD163, a marker of M2 activation. All
      three soluble receptors were measured in supernatants of monocytes/macrophages
      cultured in various immunological conditions. Membrane expression of MerTK, AXL
      and CD163 was assessed by flow cytometry. RESULTS: Both sMER and sAXL were
      associated with anti-chromatin and anti-phospholipid autoantibodies, and with
      hematological and renal involvement. However, sMER and sAXL did not significantly
      correlate with each other; sAXL correlated with growth arrest-specific 6 (Gas6),
      whereas sMER correlated with reduced free protein S (PROS) levels. Only sMER
      showed significant associations with lupus-specific anti-dsDNA, anti-Sm, anti
      ribonucleoprotein (anti-RNP) and anti-Ro60 autoantibodies. Strong correlations
      with disease activity indices (Systemic Lupus Erythematosus Disease Activity
      Index (SLEDAI), complement reduction, titer of circulating anti-dsDNA) were found
      for sMER, not for sAXL. Patients with active SLEDAI, nephritis, anti-dsDNA and
      anti-Ro60 positivity showed higher levels of sMER compared to controls. Levels of
      sMER, not sAXL, correlated with sCD163 levels, and these correlated with SLEDAI.
      Production of sMER and sCD163 occurred under "M2c" polarizing conditions, whereas
      sAXL was released upon type-I IFN exposure. CONCLUSIONS: Alterations in
      homeostasis of anti-inflammatory and efferocytic "M2c" monocytes/macrophages may
      have a role in immunopathogenesis of SLE.

PMID- 24325952
TI  - BRAF inhibitors in cancer therapy.
AB  - Activating BRAF mutations, leading to constitutive activation of the MAPK
      signaling pathway, are common in a variety of human cancers. Several small
      molecule BRAF inhibitors have been developed during the last years and shown
      promising results in clinical trials, especially for metastatic melanoma, while
      they have been less effective in colon cancer. Two inhibitors, vemurafenib and
      dabrafenib, have been approved for treatment of melanoma. Unfortunately, in most
      patients who initially respond the tumors eventually develop acquired resistance
      to the BRAF inhibitors. So far, a number of resistance mechanisms have been
      identified, including secondary NRAS mutations and BRAF alternative splicing,
      leading to reactivation of the MAPK pathway. Other alterations, both upstream and
      downstream of BRAF can have the same effect, and activation of alternative
      pathways can also play a role in resistance to BRAF inhibitors. In addition,
      intra-tumor heterogeneity with the presence of clones of tumor cells lacking BRAF
      mutations needs to be considered, since wildtype BRAF can be activated by
      inhibitors designed to target mutated BRAF. Combination of the BRAF inhibitor
      dabrafenib with the MEK inhibitor trametinib has significantly prolonged
      progression free survival compared to dabrafenib alone in metastatic melanoma.
      Combination treatments of BRAF inhibitors with other agents may not only
      circumvent or delay resistance, but may also lead to fewer side effects, such as
      development of secondary squamous tumors. Several clinical trials are underway
      for many different BRAF mutation positive cancers with BRAF inhibitors alone or
      in combination with other small molecule inhibitors, immunotherapies or
      conventional chemotherapy. 

PMID- 24325953
TI  - Transversus abdominis plane block following abdominally based breast
      reconstruction: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Breast reconstruction using the free muscle-sparing transversus
      abdominus myocutaneous or deep inferior epigastric perforator flaps are common
      methods for restoring mastectomy defects for breast cancer patients. Despite its
      increasing popularity and safety, the abdominal donor site remains a major source
      of postoperative pain. Conventional postoperative pain relief protocol consists
      primarily of a patient-controlled anesthesia device delivering intravenous
      opioids. Opioids can cause numerous side effects such as sedation, headache,
      nausea, vomiting, breathing difficulties and bladder and bowel dysfunction. A
      promising approach to provide postoperative pain control of the abdominal
      incision is the newly developed transversus abdominis plane peripheral nerve
      block. METHODS/DESIGN: This study is a double-blind, placebo-controlled,
      randomized controlled trial designed to rigorously test the effectiveness of a
      transversus abdominis plane catheter delivering intermittent local anesthetic in
      reducing postoperative abdominal pain following abdominal tissue breast
      reconstruction. The primary objective of this study is compare the mean total
      opioid consumption in the first postoperative 48 hours between the control and
      study groups including the patient-controlled anesthesia amounts and oral
      narcotic doses converted to intravenous morphine equivalent units. The secondary
      outcome measures include the following parameters: total in-hospital cumulative
      opioid consumption; daily patient-reported pain scores; total in-hospital
      cumulative anti-nausea consumption; nausea and sedation scores; and Quality of
      Recovery score; time to first bowel movement, ambulation, and duration of
      hospital stay. DISCUSSION: Autologous breast reconstruction using abdominal
      tissue is rapidly becoming the reconstructive option of choice for postmastectomy
      patients across North America. A substantial component of the pain experienced by
      patients after this abdominally based procedure is derived from the abdominal
      wall incision. By potentially decreasing the need for systemic opioids and their
      associated side effects, this transversus abdominis plane block study will
      utilize the most scientifically rigorous double-blind, placebo-controlled,
      randomized controlled trial methodology to potentially improve both clinical care
      and health outcomes in breast cancer surgery patients. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01398982.

PMID- 24325954
TI  - Invisalign technique in the treatment of adults with pre-restorative concerns.
AB  - The Invisalign method is gaining an increasing interest as an alternative
      treatment option in adult patient in multidisciplinary complex cases to simplify
      the treatment plan. The aim of this work is to show the importance of planning a
      multidisciplinary approach to respond at the esthetic requests of adult patients
      and to treat complex cases with high predictability. 

PMID- 24325955
TI  - Perioperative considerations in the management of a patient with multiple myeloma
      undergoing aortic valve replacement.

PMID- 24325956
TI  - Adenosine and bronchospasm: vigilance in the electrophysiology suite.

PMID- 24325957
TI  - Telephone calls postdischarge from hospital to home: a literature review.
AB  - The oncology population is particularly affected by hospital readmissions because
      hospitalized patients with cancer often have complex needs. The complexity and
      diversity of care requirements create substantial challenges in planning for
      appropriate postdischarge support. Implementing postdischarge telephone calls in
      the population of patients with cancer could offer a low-cost intervention to
      address the complex needs of patients during the transition from hospital to
      home. The goal of the current literature review is to provide an understanding
      about postdischarge telephone calls in patients with cancer. Findings from this
      review support the notion that discharge phone calls could improve care
      continuity for patients transitioning from hospital to home. The literature
      review outlines information related to telephone call content, timing, and
      structure for healthcare systems that want to use a postdischarge telephone
      intervention for patients with cancer. However, additional research is needed to
      develop and test cancer-specific protocols. 

PMID- 24325958
TI  - Early changes in apical rotation in genotype positive children with hypertrophic
      cardiomyopathy mutations without hypertrophic changes on two-dimensional imaging.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common form of
      inherited cardiomyopathy. Echocardiography is the mainstay of screening and
      disease surveillance, and genetic testing has identified a carrier population
      without hypertrophy. The aim of this study was to investigate whether changes in
      left ventricular (LV) function are detectable before the advent of hypertrophy.
      METHODS: Fourteen children with genotype-positive, phenotype-negative HCM were
      identified (12 male; median age, 9.14 years; range, 1.91-15.9 years; median
      weight, 34.6 kg; range, 15-92.1 kg) and compared with age-matched and sex-matched
      healthy controls. All children underwent full echocardiographic studies using an
      extensive functional protocol, including two-dimensional dimensions, Doppler
      tissue imaging, and two-dimensional speckle-tracking echocardiography. RESULTS:
      There were no differences in LV wall thickness, chamber dimensions, length, and
      shortening fraction between the groups. Doppler tissue imaging in children with
      HCM demonstrated mildly reduced septal velocities, notably A' (5.9 cm/sec [range,
      4-8.9 cm/sec] vs 6.7 cm/sec [range, 5.2-9.5 cm/sec]; P = .009). Circumferential
      and longitudinal strain was similar between groups. Mean apical circumferential
      deformation was increased in the HCM group (-24.6 +/- 3.8% vs -22.2 +/- 2.5%, P =
      .04). There were significant increases in basal and apical rotation and LV twist
      in children with HCM, most marked at the apex (11.7 +/- 4.4 degrees  vs 5.3 +/-
      2.5 degrees , P = .0001). On receiver operating characteristic curve analysis,
      apical rotation > 7 degrees  conferred 83% sensitivity and 82% specificity for
      predicting HCM (area under the curve, 0.919; P = .0001). CONCLUSIONS: Increased
      LV rotation and twist are present in children with genotype-positive, phenotype
      negative HCM. Apical rotation on speckle-tracking echocardiography provides good
      sensitivity and specificity for the prediction of gene-positive HCM and may be a
      clinically useful early marker of HCM before the onset of hypertrophy.

PMID- 24325959
TI  - Doppler tissue imaging is an independent predictor of outcome in patients with ST
      segment elevation myocardial infarction treated with primary percutaneous
      coronary intervention.
AB  - BACKGROUND: Doppler tissue imaging (DTI) detects early signs of left ventricular
      (LV) dysfunction; however, the prognostic significance of DTI after ST-segment
      elevation myocardial infarction (STEMI) is unknown. The aim of this study was to
      evaluate the prognostic value of DTI after STEMI in patients treated with primary
      percutaneous coronary intervention. METHOD: In total, 391 patients who were
      admitted with STEMIs and treated with primary percutaneous coronary intervention
      were prospectively included. All participants were examined by echocardiography 2
      days (interquartile range, 1-3 days) after STEMI. Longitudinal systolic (s'),
      early diastolic (e'), and late diastolic (a') myocardial velocities were measured
      using color DTI at six mitral annular sites and averaged to provide global
      estimates. RESULTS: The median follow-up period was 25 months (interquartile
      range, 19-32 months). The primary end point was a composite of death, heart
      failure, or a new myocardial infarction. Patients with low global systolic
      function (s') or low global diastolic function (e') had >2 times greater risk for
      the combined end point compared with patients with high global s' (hazard ratio,
      2.60; 95% confidence interval, 1.64-4.13; P < .001) or e' (hazard ratio, 2.26;
      95% confidence interval, 1.44-3.55; P < .001), respectively. After adjustment for
      age, gender, peak troponin I, previous myocardial infarction, LV ejection
      fraction, LV mass index, and LV dimension in a multivariate Cox model, patients
      with low values of both global s' and e' remained at significantly higher risk
      than patients with high s' and/or e' (hazard ratio, 1.69; 95% confidence
      interval, 1.02-2.81; P = .043). CONCLUSIONS: A pattern of low systolic and
      diastolic performance as assessed by DTI is a paramount marker of adverse
      prognosis for patients with STEMIs independent of conventional echocardiographic
      parameters. DTI velocities should be evaluated together as they interact with the
      prognosis.

PMID- 24325960
TI  - Use of three-dimensional speckle-tracking echocardiography for quantitative
      assessment of global left ventricular function: a comparative study to three
      dimensional echocardiography.
AB  - BACKGROUND: The aim of this study was to determine whether global strains derived
      from three-dimensional (3D) speckle-tracking echocardiography (STE) are as
      accurate as left ventricular (LV) ejection fraction (LVEF) obtained by two
      dimensional (2D) and 3D echocardiography in the quantification of LV function.
      METHODS: Two-dimensional and 3D echocardiography and 2D and 3D STE were performed
      in 88 patients (LVEF range, 17%-79%). Two-dimensional and 3D global longitudinal
      strain (GLS), global circumferential strain (GCS), global radial strain, and
      global area strain were quantified and correlated with LV function determined by
      2D and 3D echocardiographic LVEF. Reproducibility, feasibility, and duration of
      study to perform 3D STE were assessed by independent, blinded observers. RESULTS:
      A total of 78 patients (89%) underwent 3D STE. All 3D speckle-tracking
      echocardiographic parameters had strong correlations with assessment of LV
      function determined by 2D and 3D echocardiographic LVEF. Three-dimensional GCS
      was the best marker of LV function (r = -0.89, P < .0001). Subgroup analysis
      demonstrated that 3D speckle-tracking echocardiographic parameters were
      particularly useful in identifying LV dysfunction (LVEF < 50%). Receiver
      operating characteristic curve analysis demonstrated areas under the curve of
      0.97 for 3D GCS, 0.96 for 3D global radial strain, 0.95 for 3D global area
      strain, and 0.87 for 3D GLS. An optimal 3D GCS cutoff value of magnitude < -12%
      predicted LV dysfunction (LVEF obtained by 2D echocardiography < 50%) with 92%
      sensitivity and 90% specificity. There was good correlation between 2D GLS and 3D
      GLS (r = 0.85, P < .001; mean difference, -1.7 +/- 6.5%). Good intraobserver,
      interobserver, and test-retest agreements were seen with 3D STE. Time for image
      acquisition to postprocessing analysis was significantly reduced with 3D STE (3.7
      +/- 1.0 minutes) compared with 2D STE (4.6 +/- 1.5 min) (P < .05). CONCLUSIONS:
      Global strain by 3D STE is a promising novel alternative to quantitatively assess
      LV function. Three-dimensional STE is reproducible, feasible, and time efficient.

PMID- 24325961
TI  - Right ventricular function in acute pulmonary embolism: a combined assessment by
      three-dimensional and speckle-tracking echocardiography.
AB  - BACKGROUND: The aim of this study was to assess changes in right ventricular (RV)
      parameters determined by three-dimensional (3D) echocardiography and speckle
      tracking echocardiography in patients with acute pulmonary embolism and RV
      dysfunction without systemic hypotension (submassive pulmonary embolism).
      METHODS: Sixty-six patients were prospectively studied at the onset of the acute
      episode and after median follow-up periods of 30 days and 6 months. Sixty-six
      controls were selected. RV fractional area change, tricuspid annular plane
      systolic excursion, and myocardial performance index were determined. RV systolic
      pressure was assessed using continuous-wave Doppler echocardiography. Three
      dimensional RV ejection fraction (RVEF) was calculated. Two-dimensional peak
      systolic RV longitudinal strain (RVLS) was measured in the basal free wall, mid
      free wall (MFW), and apical free wall and the septum. RESULTS: Tricuspid annular
      plane systolic excursion and fractional area change were smaller and myocardial
      performance index was larger compared with controls (P < .05). Global RVLS (P <
      .05), MFW RVLS (P < .001), and 3D RVEF (P < .001) were lower in patients with
      pulmonary embolism than in controls. There was earlier reversal of MFW RVLS
      values on 30-day follow-up and longer reversal of 3D RVEF and RV systolic
      pressure values at 6-month follow-up. Receiver operating characteristic curve
      analysis showed that changes in 3D RVEF and MFW RVLS were the most sensitive
      predictors of adverse events. By multivariate analysis, RV systolic pressure (P =
      .007), MFW RVLS (P = .002), and 3D RVEF (P = .001) were independently associated
      with adverse outcomes. CONCLUSIONS: Acute submassive pulmonary embolism has a
      significant impact on RV function as assessed by 3D echocardiography and speckle
      tracking echocardiography. Decreases in MFW RVLS and 3D RVEF may persist during
      short-term and long-term follow-up and correlate with unfavorable outcomes.

PMID- 24325962
TI  - Right ventricular to left ventricular diameter ratio at end-systole in evaluating
      outcomes in children with pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) increases right ventricular (RV)
      pressure, resulting in septal shift and RV dilation. Few echocardiographic
      measures have been used to evaluate severity and outcomes in children with PH.
      The aims of this study were to compare the RV to left ventricular (LV) diameter
      ratio at end-systole (RV/LV ratio) in normal controls and patients with PH, to
      correlate the RV/LV ratio with invasive hemodynamic measures, and to evaluate its
      association with outcomes in children with PH. METHODS: The RV/LV ratio was
      compared retrospectively between 80 matched normal controls and 84 PH patients
      without shunts. Of the patients with PH, 49 children underwent 94
      echocardiographic studies and cardiac catheterizations within 48 hours (13
      patients had simultaneous measurements). The RV/LV ratio was correlated against
      hemodynamic measures. Kaplan-Meier curves and a Cox proportional-hazards
      regression model were used to assess relationships between RV/LV ratio and time
      until an adverse clinical event (initiation of intravenous prostacyclin therapy,
      atrial septostomy, death, or transplantation). RESULTS: RV/LV ratios were lower
      in controls compared with patients with PH (mean, 0.51 [95% confidence interval,
      0.48-0.54] vs 1.47 [95% confidence interval, 1.25-1.70], P < .01). The RV/LV
      ratio correlated significantly with mean pulmonary artery pressure, systolic
      pulmonary artery pressure, systolic pulmonary artery pressure as a percentage of
      systemic pressure, and pulmonary vascular resistance index (r = 0.65 [P < .01], r
      = 0.6 [P < .01], r = 0.49 [P < .01], and r = 0.43 [P < .01], respectively).
      Twenty-two patients with PH with RV/LV ratios > 1 had adverse events within a
      median of 1.1 years from their earliest echocardiographic studies. Increasing
      RV/LV ratio was associated with an increasing hazard for a clinical event (hazard
      ratio, 2.49; 95% confidence interval, 1.92-3.24). CONCLUSIONS: The RV/LV end
      systolic diameter ratio can easily be obtained noninvasively in the clinical
      setting and can be used in the management of patients with PH. The RV/LV ratio
      incorporates both pathologic septal shift and RV dilation in children with PH and
      correlates with invasive measures of PH. An RV/LV ratio > 1 is associated with
      adverse clinical events.

PMID- 24325963
TI  - Toll-like receptor polymorphism associations with HIV-1 outcomes among sub
      Saharan Africans.
AB  - OBJECTIVE: We evaluated Toll-like receptors (TLRs) single nucleotide
      polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and
      disease progression in African couples. METHODS: Seven candidate and 116
      haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and
      343 seronegative controls. RESULTS: TLR9 1635A/G was associated with reduced HIV
      1 acquisition among HIV-seronegative controls with high but not low HIV-1
      exposure (odds ratio [OR] = 0.7; P = .03 and OR = 0.9, P = .5, respectively).
      TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time
      since HIV-1 acquisition. TLR8 1A/G reduced disease progression. CONCLUSIONS: TLR
      SNPs impact HIV-1 outcomes with epidemiologic factors modifying these
      relationships.

PMID- 24325964
TI  - Survey of human antibody responses to influenza virus matrix protein 2 by use of
      a sensitive flow cytometric method.

PMID- 24325965
TI  - Serum antibody response to matrix protein 2 following natural infection with 2009
      pandemic influenza A(H1N1) virus in humans.
AB  - Natural infection-induced humoral immunity to matrix protein 2 (M2) of influenza
      A viruses in humans is not fully understood. Evidence suggests that anti-M2
      antibody responses following influenza A virus infection are weak and/or
      transient. We show that the seroprevalence of anti-M2 antibodies increased with
      age in 317 serum samples from healthy individuals in the United States in 2007
      2008. Infection with 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) elicited
      a recall serum antibody response to M2 protein of A(H1N1)pdm09 in 47% of the
      affected 118 individuals tested. Anti-M2 antibody responses were more robust
      among individuals with preexisting antibodies to M2 protein. Moreover, the
      antibodies induced as a result of infection with A(H1N1)pdm09 were cross-reactive
      with M2 protein of seasonal influenza A viruses. These results emphasize the need
      to further investigate the possible roles of anti-M2 antibodies in human
      influenza A virus infection. 

PMID- 24325966
TI  - Monocyte activation by interferon alpha is associated with failure to achieve a
      sustained virologic response after treatment for hepatitis C virus infection.
AB  - BACKGROUND: Interferon alpha (IFN-alpha) and ribavirin can induce a sustained
      virologic response (SVR) in some but not all hepatitis C virus (HCV)-infected
      patients. The mechanism of effective treatment is unclear. One possibility is
      that IFN-alpha differentially improves the functional capacity of classic myeloid
      dendritic cells (mDCs) by altering expression of surface molecules or cytokines.
      Others have proposed that antigen-presenting cell activation could be
      paradoxically detrimental during HCV infection because of the production by
      monocytes of substances inhibitory or toxic to plasmacytoid dendritic cells.
      METHODS: We examined responses to in vitro IFN-alpha treatment of peripheral
      blood leukocyte samples from a retrospective treatment cohort of nearly 200 HCV
      seropositive patients who had undergone antiviral therapy with ribavirin and
      pegylated IFN. We analyzed the variable responses of antigen-presenting cell
      subsets to drug. RESULTS: We found that patients achieving SVR were no more
      likely to have robust mDC activation in response to IFN-alpha than those who did
      not achieve SVR. Rather, patients achieving SVR were distinguished by restrained
      monocyte activation in the presence of IFN-alpha, a factor that was second in
      importance only to IL28B genotype in its association with SVR. CONCLUSIONS: These
      results suggest that interindividual variability in the response of monocytes to
      IFN-alpha is an important determinant of treatment success with IFN-alpha-based
      regimens.

PMID- 24325968
TI  - Insight into the pathogenesis of fetal growth restriction in placental malaria:
      decreased placental glucose transporter isoform 1 expression.
AB  - Placental malaria, especially when complicated with intervillositis, can cause
      fetal growth restriction. Transplacental glucose transport by glucose transporter
      isoform 1 (GLUT-1) on the syncytiotrophoblast microvillous and basal plasma
      membranes regulates fetal growth. We found that GLUT-1 expression in the
      microvillous plasma membrane of Plasmodium falciparum-negative placenta biopsy
      specimens was comparable to that in P. falciparum-positive placenta biopsy
      specimens with or without intervillositis, whereas GLUT-1 expression in the basal
      plasma membrane was lowest in P. falciparum-positive placenta biopsy specimens
      with intervillositis, compared with the other 2 specimen types (P <= .0016). GLUT
      1 expression in the basal plasma membrane also correlated negatively with
      monocyte infiltrate density (r = -0.43; P = .003) and positively with birth
      weight (r = 0.28; P = .06). These findings suggest that intervillositis, more
      than placental malaria per se, might cause fetal growth restriction, through
      impaired transplacental glucose transport. 

PMID- 24325967
TI  - Cord blood Vgamma2Vdelta2 T cells provide a molecular marker for the influence of
      pregnancy-associated malaria on neonatal immunity.
AB  - BACKGROUND: Plasmodium falciparum placental infection primes the fetal immune
      system and alters infant immunity. Mechanisms leading to these outcomes are not
      completely understood. We focused on Vgamma2Vdelta2 cells, which are part of the
      immune response against many pathogens, including P. falciparum. These
      unconventional lymphocytes respond directly to small, nonpeptidic antigens,
      independent of major histocompatibility complex presentation. We wondered whether
      placental malaria, which may increase fetal exposure to P. falciparum
      metabolites, triggers a response by neonatal Vgamma2Vdelta2 lymphocytes that can
      be a marker for the extent of fetal exposure to malarial antigens. METHODS: Cord
      blood mononuclear cells were collected from 15 neonates born to mothers with P.
      falciparum infection during pregnancy (8 with placental malaria) and 25 unexposed
      neonates. Vgamma2Vdelta2 cell phenotype, repertoire, and proliferative responses
      were compared between newborns exposed and those unexposed to P. falciparum.
      RESULTS: Placental malaria-exposed neonates had increased proportions of central
      memory Vgamma2Vdelta2 cells in cord blood, with an altered Vgamma2 chain
      repertoire ex vivo and after stimulation. CONCLUSION: Our results suggest that
      placental malaria affects the phenotype and repertoire of neonatal Vgamma2Vdelta2
      lymphocytes. Placental malaria may lower the capacity for subsequent
      Vgamma2Vdelta2 cell responses and impair the natural resistance to infectious
      diseases or the response to pediatric vaccination.

PMID- 24325969
TI  - Biochemical responses of ecological importance in males of the austral South
      America amphipod Hyalella curvispina Shoemaker, 1942 exposed to waterborne
      cadmium and copper.
AB  - The use of physiological parameters as sensitive indicators of toxic stress from
      exposure to different pollutants is an important issue to be studied. Hyalella
      curvispina is a Neotropical amphipod often used in ecotoxicological evaluations.
      This work aimed to quantify biochemical responses of ecological importance in H.
      curvispina males under stress exposure to sublethal concentrations of waterborne
      copper (Cu) and cadmium (Cd); in order to obtain basic physiological data as
      indicators of early effect on this species, on track to its standardization. In
      order to evaluate the physiological, biochemical and energetic status of the
      exposed animals, the following endpoints were selected: content of glycogen,
      total proteins, total lipids, triglycerides, glycerol, arginine, arginine
      phosphate, levels of lipid peroxidation (TBARS), and Na(+)/K(+)ATPase, catalase
      (CAT) and superoxide dismutase (SOD) activities. Our results show that the
      concentrations of Cu (135 and 175 ug/L) and Cd (6.5 and 10.5 ug/L) tested altered
      most of the biochemical variables measured (glycogen, total proteins, total
      lipids, triglycerides, arginine phosphate, TBARS, and SOD and Na(+)/K(+)ATPase
      activities). In addition, neither the levels of glycerol and arginine nor CAT
      activity were affected by exposure to either metal. Energy metabolism was
      similarly affected both by exposure to Cu and exposure to Cd. The results
      obtained show the existence of an energy imbalance associated with oxidative
      damage, suggesting a comprehensive response. This work represents a first
      contribution of the evaluation of the effect of two heavy metals in some
      parameters of oxidative stress and energy metabolism of H. curvispina males. The
      results indicate these parameters can provide a sensitive criterion for the
      assessment of early ecotoxicological effects of Cu and Cd in laboratory assays,
      on a native species representative of the zoobenthic and epiphytic communities of
      South America.

PMID- 24325970
TI  - Low-dose protocol of the spiral CT in orthodontics: comparative evaluation of
      entrance skin dose with traditional X-ray techniques.
AB  - BACKGROUND: The aim of this study was to evaluate the amount of radiation doses
      absorbed by soft tissues (entrance skin dose) with a low-dose spiral computed
      tomography (CT) protocol compared to conventional X-ray techniques commonly used
      in orthodontics. METHODS: The amount of skin dose has been evaluated using a
      tissue-equivalent head-neck radiotherapy humanoid phantom with thermoluminescent
      dosimeters placed at the level of eye lens, parotid glands, and thyroid glands.
      CT images have been taken using a Sensation 16 Siemens CT scan and a low-dose
      protocol (15 mAs, 1 pitch, 2.5 mGy (CTDIvol), 80 kV, 1-mm slice thickness).
      RESULTS: The difference in image quality between traditional X-ray techniques and
      low-dose spiral CT was statistically significant (P<0.05). The difference in mean
      absorbed dose instead was not statistically significant. CONCLUSIONS: Our
      protocol allows a more accurate orthodontic diagnosis without an increase of
      radiological risk for the patients in comparison to traditional X-ray techniques.

PMID- 24325971
TI  - How useful are complete blood count and reticulocyte reports to clinicians in
      Addis Ababa hospitals, Ethiopia?
AB  - BACKGROUND: Complete blood count (CBC) and reticulocyte (Retics) are routine
      hematology tests useful for the differential diagnosis of anemia and other
      medical conditions. However, it has been presumed that they are not used as
      regular as they should be in medical practice in Addis Ababa hospitals. METHODS:
      A hospital-based cross-sectional questionnaire survey was conducted during
      November-December 2010, in which 408 clinicians participated and their response
      on the use of CBC and Retics was assessed. The always/frequently (A/F) response
      was considered to reflect routine use of the CBC/Retics parameters by the
      clinicians. The Chi square test was used to study statistical associations among
      different variables. RESULT: Only four of 13 parameters in CBC were frequently or
      always used by more than 85% of the clinicians. Health Officers were observed to
      use 12 of the 13 CBC parameters less than the other professional group; interns
      and residents demonstrated highest use of CBC results. More than a third of
      clinicians' preferred white blood cell (WBC) differential report in percentages
      than the more useful absolute number report. Reticulocyte parameters were not
      being used by majority of clinicians in patient management. Clinicians rated
      'average' regarding the adequacy of clinical laboratory methods course they took
      during medical education. As service users, clinicians indicated mm3 as unit of
      preference in cell count on the laboratory report form. CONCLUSION: Overall, most
      clinicians do not use much of the data provided on routine CBC report. Additional
      research is needed to understand the issue further. Responsible bodies should
      promote the appropriate use of CBC/Retics reports by clinicians.

PMID- 24325972
TI  - Cell damage induced by copper: an explant model to study anemone cells.
AB  - Sea anemones are benthic organisms, of low mobility and can be directly affected
      by water pollution. This work studied the defense mechanisms and DNA damage
      caused by copper toxicity in cells from the anemone Bunodosoma cangicum. For
      this, exposure of anemones cells were held, kept in primary culture through
      explant of podal disk to copper (7.8 and 15.6 MUg/L), and the control group, for
      6 and 24h. Cytotoxicity was seen through the viability and cell number, MXR
      phenotype through the accumulation of rhodamine-B, ROS generation by H2DCF-DA and
      DNA damage by comet assay. The results obtained show that there is a drop in
      viability and number of cells, especially after exposure of 24h in 15.6 MUg/L.
      There is an induction of the MXR activity only at 7.8 MUg/L for 24h. As for ROS,
      there is an increase in the generation of reactive species in greatest
      concentration of copper for 6h, and in both for 24h, which leads to oxidative
      stress, which culminates with a DNA damage. What was evidenced by the increase of
      the tail size, % DNA presented and moment of tail. Therefore, the copper
      represents an adversity to the anemones cells, being cytotoxic and genotoxic.

PMID- 24325973
TI  - An atypical case of choroidal neovascularization associated with pseudoxanthoma
      elasticum treated with intravitreal bevacizumab: a case report.
AB  - BACKGROUND: Pseudoxanthoma elasticum is an inherited disorder that is associated
      with accumulation of pathologic elastic fibers in the skin, vascular walls and
      Bruch's membrane in the eye. Choroidal neovascularization is one of the most
      common causes of acute vision loss in these patients. We report an atypical case
      of suspected choroidal neovascularization associated with pseudoxanthoma
      elasticum. CASE PRESENTATION: A 47-year-old Caucasian woman with pseudoxanthoma
      elasticum and angioid streaks was referred because of decreased and distorted
      vision in her right eye of one week's duration. Visual acuity was 6/12 in the
      right eye and 6/6 in the left eye. Fundus examination revealed angioid streaks
      and white intraretinal macular deposits bilaterally. Fluorescein angiography did
      not reveal any obvious leakage in the right eye while optical coherence
      tomography revealed subretinal fluid associated with an adjacent intraretinal
      hyperreflective structure. Autofluoresence imaging showed focal areas of
      increased autofluorescence corresponding to the deposits in both eyes. Over the
      following year the patient underwent five intravitreal injections of bevacizumab
      (Genentech/Roche,US) in the right eye, which resulted in visual acuity improving
      to 6/9 with regression of the hyperreflective structrure and complete resolution
      of subretinal fluid. CONCLUSIONS: Traditionally, fluorescein angiography is
      effective in the detection of choroidal neovascularization in patients with
      pseudoxanthoma elasticum. In our case, optical coherence tomography revealed
      subretinal fluid and an adjacent hyperreflective structure while fluorescein
      angiography did not reveal any obvious leakage. The sole presence of subretinal
      fluid does not necessarily imply the presence of choroidal neovascularization and
      certainly retinal pigment epithelium dysfunction could also explain subretinal
      fluid in these patients. However, the complete absorption of the fluid and the
      disappearance of the previously evident hyperreflective structure following
      treatment, led us to suspect choroidal neovascularization as the primary cause of
      the above findings. The poor natural course of choroidal neovascularization in
      these patients increases the importance of early detection and should result in
      the adaptation of a low-threshold strategy concerning the initiation of
      treatment.

PMID- 24325974
TI  - The effect of interlocking parallel screws in subcapital femoral-neck fracture
      fixation: a cadaver study.
AB  - BACKGROUND: A new locking-plate for femoral-neck fractures that provides angular
      stability to three screws in an inverted triangle configuration was evaluated.
      The plate is not fixed to the lateral cortex and therefore represents a new
      treatment principle. METHODS: Twelve pairs of cadaver femurs (mean T-score -1,95
      (range -4,5-0)) with subcapital femoral-neck fractures angulating 60 degrees 
      were randomly allocated to fracture-fixation using either three individual screws
      or three interlocked screws. Subject-specific axial force and torque were applied
      by a hip simulator and three-dimensional migrations were recorded. The femurs
      underwent 10,000 cycles of simulated partial weight-bearing, followed by 10,000
      cycles of simulated full weight-bearing and stair climbing. FINDINGS: On average
      interlocking reduced femoral-head centre migrations 1.6mm (95% CI 0.1-3.1, P =
      0.04). The intra-pair correlation of migration was 0.953 (Pearson's r).
      Interlocking did not change rotational stability (P = 0.87). Adding a locking
      plate did not affect the risk of failure, however all failed femurs were fixed
      using the smallest-sized aiming guide. INTERPRETATIONS: Adding a lateral
      interlocking plate to three screws might improve the fracture stability. However,
      none of the implants were able to resist the unwanted deformation of the proximal
      femur. Regardless of the fixation, female sex, reduced bone quality and small
      sized femurs appear to increase risk of failure.

PMID- 24325975
TI  - Decreased resting-state interhemispheric functional connectivity in unaffected
      siblings of schizophrenia patients.
AB  - BACKGROUND: Neuroimaging studies in unaffected siblings of schizophrenia patients
      can provide clues to the pathophysiology for the development of schizophrenia.
      However, little is known about the alterations of the interhemispheric resting
      state functional connectivity (FC) in siblings, although the dysconnectivity
      hypothesis is prevailing in schizophrenia for years. In the present study, we
      used a newly validated voxel-mirrored homotopic connectivity (VMHC) method to
      identify whether aberrant interhemispheric FC was present in unaffected siblings
      at increased risk of developing schizophrenia at rest. METHODS: Forty-six
      unaffected siblings of schizophrenia patients and 50 age-, sex-, and education
      matched healthy controls underwent a resting-state functional magnetic resonance
      imaging (fMRI). Automated VMHC was used to analyze the data. RESULTS: The sibling
      group had lower VMHC than the control group in the angular gyrus (AG) and the
      lingual gyrus/cerebellum lobule VI. No region exhibited higher VMHC in the
      sibling group than in the control group. There was no significant sex difference
      of the VMHC values between male siblings and female siblings or between male
      controls and female controls, although evidence has been accumulated that size
      and shape of the corpus callosum, and functional homotopy differ between men and
      women. CONCLUSIONS: Our results first suggest that interhemispheric resting-state
      FC of VMHC is disrupted in unaffected siblings of schizophrenia patients, and add
      a new clue of abnormal interhemispheric resting-state FC to the pathophysiology
      for the development of schizophrenia.

PMID- 24325976
TI  - Attenuated prefrontal activation during decision-making under uncertainty in
      schizophrenia: a multi-center fMRI study.
AB  - Decisions are called decisions under uncertainty when either prior information is
      incomplete or the outcomes of the decision are unclear. Alterations in these
      processes related to decisions under uncertainty have been linked to delusions.
      In patients with schizophrenia, the underlying neural networks have only rarely
      been studied. We aimed to disentangle the neural correlates of decision-making
      and relate them to neuropsychological and psychopathological parameters in a
      large sample of patients with schizophrenia and healthy subjects. Fifty-seven
      patients and fifty-seven healthy volunteers from six centers had to either
      indicate via button-press from which of two bottles red or blue balls were drawn
      (decision-making under uncertainty condition), or indicate whether eight red
      balls had been presented (baseline condition) while BOLD signal was measured with
      fMRI. Patients based their decisions on less conclusive evidence and had
      decreased activations in the underlying neural network, comprising of medial and
      lateral frontal as well as parietal areas, as compared to healthy subjects. While
      current psychopathology was not correlated with brain activation, positive
      symptoms led to longer decision latencies in patients. These results suggest that
      decision-making under uncertainty in schizophrenia is affected by a complex
      interplay of aberrant neural activation. Furthermore, reduced neuropsychological
      functioning in patients was related to impaired decision-making and task
      performance was modulated by distinct positive symptoms. 

PMID- 24325977
TI  - Cognition impairment in schizophrenia patients with tardive dyskinesia:
      association with plasma superoxide dismutase activity.
AB  - Long-term antipsychotic treatment for schizophrenia is often associated with the
      emergence of tardive dyskinesia (TD), and TD presence is also accompanied by more
      severe cognitive impairment. Oxidative stress-induced damage may be involved in
      the development of TD and contribute to cognitive deficits in schizophrenia. We
      examined the role of oxidative stress in relation to TD and cognitive deficits in
      schizophrenia using plasma manganese superoxide dismutase (MnSOD) as a biomarker.
      We recruited 83 male chronic patients with (n=32) and without TD (n=51) meeting
      DSM-IV criteria for schizophrenia, and 58 male control subjects. We examined the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and
      MnSOD activity for all subjects. Positive and Negative Symptom Scale (PANSS) and
      the Abnormal Involuntary Movement Scale (AIMS) were assessed in the patients.
      MnSOD activity was lower in patients with TD than non-TD, and either TD or non-TD
      group had lower MnSOD levels than controls (all p<0.05). Patients with TD had
      lower RBANS total (p<0.05) and Visuospatial/Constructional subscale scores than
      non-TD patients (p<0.01), and either TD or non-TD group scored lower than the
      controls on all RBANS subscales (all p<0.001) except for the
      Visuospatial/Constructional index. Multiple regression analysis showed that in
      either TD or non-TD group, MnSOD was an independent contributor to the RBANS
      total score (both p<0.05). These findings suggest that TD patients suffered
      oxidative stress and cognition impairment at a more severe level than non-TD
      patients. Oxidative stress might serve as a functionally linking node between TD
      development and cognition dysfunction in schizophrenia. 

PMID- 24325978
TI  - Sclerosing bone dysplasias with involvement of the craniofacial skeleton.
AB  - In this review we provide a complete overview of the existing sclerosing bone
      dysplasias with craniofacial involvement. Clinical presentation, disease course,
      the craniofacial symptoms, genetic transmission pattern and pathophysiology are
      discussed. There is an emphasis on radiologic features with a large collection of
      CT and MRI images. In previous reviews the craniofacial area of the sclerosing
      bone dysplasias was underexposed. However, craniofacial symptoms are often the
      first symptoms to address a physician. The embryology of the skull and skull base
      is explained and illustrated for a better understanding of the affected areas. 

PMID- 24325979
TI  - Iron and fibroblast growth factor 23 in X-linked hypophosphatemia.
AB  - BACKGROUND: Excess fibroblast growth factor 23 (FGF23) causes hypophosphatemia in
      autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia
      (XLH). Iron status influences C-terminal FGF23 (incorporating fragments plus
      intact FGF23) in ADHR and healthy subjects, and intact FGF23 in ADHR. We
      hypothesized that in XLH serum iron would inversely correlate to C-terminal
      FGF23, but not to intact FGF23, mirroring the relationships in normal controls.
      METHODS: Subjects included 25 untreated outpatients with XLH at a tertiary
      medical center and 158 healthy adult controls. Serum iron and plasma intact FGF23
      and C-terminal FGF23 were measured in stored samples. RESULTS: Intact FGF23 was
      greater than the control mean in 100% of XLH patients, and >2SD above the control
      mean in 88%, compared to 71% and 21% respectively for C-terminal FGF23. In XLH,
      iron correlated negatively to log-C-terminal FGF23 (r=-0.523, p<0.01), with a
      steeper slope than in controls (p<0.001). Iron was not related to log-intact
      FGF23 in either group. The log-ratio of intact FGF23 to C-terminal FGF23 was
      higher in XLH (0.00+/-0.44) than controls (-0.28+/-0.21, p<0.01), and correlated
      positively to serum iron (controls r=0.276, p<0.001; XLH r=0.428, p<0.05), with a
      steeper slope in XLH (p<0.01). CONCLUSION: Like controls, serum iron in XLH is
      inversely related to C-terminal FGF23 but not intact FGF23. XLH patients are more
      likely to have elevated intact FGF23 than C-terminal FGF23. The relationships of
      iron to FGF23 in XLH suggest that altered regulation of FGF23 cleaving may
      contribute to maintaining hypophosphatemia around an abnormal set-point.

PMID- 24325980
TI  - Potentiometric sensors doped with biomolecules as a new approach to small
      molecule/biomolecule binding kinetics analysis.
AB  - The most successful binding kinetics analysis systems at this moment include
      surface plasmon resonance (SPR), quartz microcrystal balance (QMB) and surface
      acoustic wave (SAW). Although these are powerful methods, they generally are
      complex, expensive and require the use of monolayers. Here, we report on
      potentiometric sensors as an inexpensive and simple alternative to do binding
      kinetics analysis between small molecules in solution and biomolecules
      (covalently) attached in a biopolymer sensor coating layer. As an example,
      dopamine and an anti-dopamine aptamer were used as the small molecule and the
      biomolecule respectively. Binding between both follows a Langmuir adsorption type
      model and creates a surface potential. The system operates in Flow Injection
      Analysis mode (FIA). Besides being an interesting new binding kinetics tool, the
      approach allows systematic design of potentiometric biosensors (in the present
      study a dopamine sensor), and gives new insights into the functioning of ion
      selective electrodes (ISE's). 

PMID- 24325981
TI  - Novel tungsten carbide nanorods: an intrinsic peroxidase mimetic with high
      activity and stability in aqueous and organic solvents.
AB  - Tungsten carbide nanorods (WC NRs) are demonstrated for the first time to possess
      intrinsic peroxidase-like activity towards typical peroxidase substrates, such as
      3, 3', 5, 5'-tetramethylbenzidine (TMB) and omicron-phenylenediamine (OPD) in the
      presence of hydrogen peroxide (H2O2). The reactions catalyzed by these nanorods
      follow the Michaelis-Menten kinetics. The excellent catalytic performance of WC
      NRs could be attributed to their intrinsic catalytic activity to efficiently
      accelerate the electron-transfer process and facilitate the decomposition of H2O2
      to generate more numbers of reactive oxygen species (ROS). Based upon the strong
      peroxidase-like activity of these WC NRs, a colorimetric sensor for H2O2 is
      designed, which provides good response towards H2O2 concentration over a range of
      2*10(-7)-8*10(-5) M with a detection limit of 60 nM. Moreover, the peroxidase
      like activities of WC NRs with TMB as the substrate are investigated in both
      protic and aprotic organic media, showing different colorimetric reactions from
      that performed in aqueous solutions. In comparison with the natural horse radish
      peroxidase, WC NR exhibits excellent robustness of catalytic activity and
      considerable reusability, thus making it a promising mimic of peroxidase
      catalysts.

PMID- 24325982
TI  - Facile synthesis of tetragonal columnar-shaped TiO2 nanorods for the construction
      of sensitive electrochemical glucose biosensor.
AB  - A tetragonal columnar-shaped TiO2 (TCS-TiO2) nanorods are synthesized via a
      facile route for the immobilization of glucose oxidase (GOx). A novel
      electrochemical glucose biosensor is constructed based on the direct
      electrochemistry of GOx at TCS-TiO2 modified glassy carbon electrode. The
      fabricated biosensor is characterized by scanning electron microscopy, Fourier
      transform infrared spectroscopy, electrochemical impedance spectra and cyclic
      voltammetry. The immobilized enzyme molecules on TCS-TiO2 nanorods retain its
      native structure and bioactivity and show a surface controlled, quasi-reversible
      and fast electron transfer process. The TCS-TiO2 nanorods have large surface area
      and provide a favorable microenvironment for enhancing the electron transfer
      between enzyme and electrode surface. The constructed glucose biosensor shows
      wide linear range from 5.0*10(-6) to 1.32*10(-3) M with a high sensitivity of
      23.2 mA M(-1) cm(-2). The detection limit is calculated to be 2.0*10(-6) M at
      signal-to-noise of 3. The proposed glucose biosensor also exhibits excellent
      selectivity, good reproducibility, and acceptable operational stability.
      Furthermore, the biosensor can be successfully applied in the detection of
      glucose in serum sample at the applied potential of -0.50 V. The TCS-TiO2
      nanorods provide an efficient and promising platform for the immobilization of
      proteins and development of excellent biosensors.

PMID- 24325983
TI  - Graphene-based potentiometric biosensor for the immediate detection of living
      bacteria.
AB  - In this communication we present a potentiometric aptasensor based on chemically
      modified graphene (transducer layer of the aptasensor) and aptamers (sensing
      layer). Graphene oxide (GO) and reduced graphene oxide (RGO) are the basis for
      the construction of two versions of the aptasensor for the detection of a
      challenging living organism such as Staphylococcus aureus. In these two versions,
      DNA aptamers are either covalently (in the GO case) or non-covalently (in the RGO
      case) attached to the transducer layer. In both cases we are able to selectively
      detect a single CFU/mL of S. aureus in an assay close to real time, although the
      noise level associated to the aptasensors made with RGO is lower than the ones
      made with GO. These new aptasensors, that show a high selectivity, are
      characterized by the simplicity of the technique and the materials used for their
      construction while offering ultra-low detection limits in very short time
      responses in the detection of microorganisms. 

PMID- 24325984
TI  - A miniaturized nanobiosensor for choline analysis.
AB  - A novel reusable chemiluminescence choline nanobiosensor has been developed using
      aligned zinc oxide nanorod-films (ZnONR). The chemically fashioned ZnONR were
      synthesized by hybrid wet chemical route onto glass substrates and used to
      fabricate a stable chemiluminescent choline biosensor. The biosensor was
      constructed by co-immobilization of the enzymes choline oxidase and peroxidase.
      The covalent immobilization of the enzymes on the ZnONR was achieved using 16
      phosphonohexadecanoic acid as a cross-linker. The phosphonation of the ZnONR
      imparted significant stability to the immobilized enzyme as against physisorbed
      enzyme. A lower value of Michaelis-Menten constant (Km), of 0.062 mM for the
      covalently coupled enzyme over the physisorbed enzymes facilitated enhanced
      stability of ZnONR nanobiosensor. The ZnONR-choline biosensor has been
      investigated over a wide range of choline from 0.0005 mM to 2 mM. Importantly,
      the recovery of choline in milk samples was close to 99%. Using the developed
      biosensor, choline was measurable even after 30 days with 60 repeated
      measurements proving the stability of the sensor (Intraday RSD%=2.83 and Interday
      RSD%=3.51).

PMID- 24325986
TI  - What is the effect of postoperative scapular fracture on outcomes of reverse
      shoulder arthroplasty?
AB  - BACKGROUND: Postoperative scapular fracture is a common complication after
      reverse shoulder arthroplasty (RSA). The purpose of this study was to determine
      its effect on RSA patient outcomes. METHODS: A retrospective, case-control study
      of 25 nonoperatively treated postoperative scapular fractures after RSA were
      analyzed with a minimum 2-year follow-up from surgery and 1-year follow-up from
      fracture. Eligible patients were matched 1:4 to a control group for age, sex,
      follow-up time, surgery indication, and primary operation vs revision. Outcome
      measures, including American Shoulder and Elbow Surgeons (ASES) score and range
      of motion, were compared between fracture cases and controls. Also analyzed were
      radiographic features, including fracture location (acromion vs scapular spine)
      and healing. RESULTS: Incidence of scapular fracture after RSA in this series was
      3.1%. Fractures occurred from 1 to 94 months postoperatively. The revision rate
      was higher in the fracture group (8% vs. 2%) but did not reach statistical
      significance (P = .18). Fracture patients had improved (DeltaASES, 21) but
      inferior clinical outcomes, with a postoperative ASES score of 58.0 compared with
      74.2 (P <= .001). Change in range of motion also diminished in the fracture
      group, with a mean gain of 26 degrees  forward elevation compared with 76 degrees
      (P < .001). Fracture location (P = .54) or healing (P = .40) did not affect
      outcome. CONCLUSION: Postoperative scapular fractures may occur at any point
      postoperatively; increasing incidence is likely as longer follow-up becomes
      available. This complication leads to inferior clinical results compared with
      controls. However, patients show improvement compared with their preoperative
      measurements, even at longer-term follow-up. Patients with postoperative scapular
      fractures may have increased risk of revision. LEVEL OF EVIDENCE: Level III, case
      control study, treatment study.

PMID- 24325985
TI  - Automated analysis of intracellular calcium fluorescence in rat organotypic
      hippocampal cultures: comparison to a manual, observer based method.
AB  - The technical advances made in microscopy have been matched by an increase in the
      application of fluorescent microscopy to answer scientific questions. While
      analysis of fluorescent microscopy images represents a powerful tool, one must be
      aware of the potential pitfalls. Frequently, the analysis methods applied involve
      at least some manual steps which are dependent on an observers input. Typically
      these steps are laborious and time consuming, but more importantly they are also
      influenced by an individual observer's bias, drift or imprecision. This raises
      concerns about the repeatability and definitiveness of the reported observations.
      Using calcium fluorescence in organotypic hippocampal slices as an experimental
      platform, we demonstrate the influence that manual interventions can exert on an
      analysis. We show that there is a high degree of variability between observers,
      and that this can be sufficient to affect the outcome of an experiment. To
      counter this, and to eliminate the disagreement between observers, we describe an
      alternative fully automated method which was created using EBImage package for R.
      This method has the added advantage of being fully open source and customisable,
      allowing for this approach to be applied to other analyses. 

PMID- 24325987
TI  - Corticosteroid injection for shoulder pain: single-blind randomized pilot trial
      in primary care.
AB  - BACKGROUND: Shoulder pain is a very common presentation in primary care. Evidence
      of benefit for subacromial corticosteroid injection is inconclusive and confined
      largely to studies with short follow-up. We plan a large, definitive, primary
      care-based trial to determine efficacy and safety in patients with rotator cuff
      tendinopathy, and conducted a pilot trial to explore feasibility. METHODS: Six
      general practitioners (GPs) from Oxfordshire, UK underwent update training in
      assessing painful shoulders and injecting the subacromial space. Each then
      recruited patients aged 35 to 74 years from primary care complaining of shoulder
      pain lasting no more than 6 months. Eligible participants were randomized to
      receive either methylprednisolone acetate 40 mg with lidocaine 1% (total volume 1
      ml), or lidocaine 1% alone (total volume 1 ml), injected into the subacromial
      space. The participants were blinded to treatment allocation. Feasibility
      outcomes were rates of recruitment, withdrawal, adherence to the protocol,
      completeness of follow-up, and success of patient masking. Clinical outcomes were
      the Oxford Shoulder Score (OSS) at baseline and at 4 and 12 weeks, and responses
      to three satisfaction questions at 2, 4 and 12 weeks. Outcome data were collected
      by postal questionnaires. RESULTS: A total of 40 participants were randomized
      (80% of the target 50 participants) over 26 weeks giving an overall recruitment
      rate of 1.5 participants per week. Rates of follow-up were maintained to a high
      level for the full 12 weeks. Four participants requested a 'rescue'
      corticosteroid injection but no patients withdrew. The trial GPs gave high scores
      for their confidence that the patient had remained blinded to treatment
      allocation during the procedure. The OSS at 4 and 12 weeks and the responses to
      the satisfaction questions are reported. CONCLUSIONS: It is feasible to recruit
      participants with shoulder pain in the primary care setting for a blinded,
      randomized trial of corticosteroid injection. Online randomization of
      participants from the practice is also feasible, and postal questionnaires
      provide an effective means of gathering outcome data in this area of study. The
      lessons learned from this pilot will usefully inform the design of a large,
      definitive efficacy trial in primary care. TRIAL REGISTRATION: Current Clinical
      Trials ISRCTN82357435.

PMID- 24325988
TI  - The cytokine and chemokine expression profile of nucleus pulposus cells:
      implications for degeneration and regeneration of the intervertebral disc.
AB  - INTRODUCTION: The aims of these studies were to identify the cytokine and
      chemokine expression profile of nucleus pulposus (NP) cells and to determine the
      relationships between NP cell cytokine and chemokine production and the
      characteristic tissue changes seen during intervertebral disc (IVD) degeneration.
      METHODS: Real-time q-PCR cDNA Low Density Array (LDA) was used to investigate the
      expression of 91 cytokine and chemokine associated genes in NP cells from
      degenerate human IVDs. Further real-time q-PCR was used to investigate 30
      selected cytokine and chemokine associated genes in NP cells from non-degenerate
      and degenerate IVDs and those from IVDs with immune cell infiltrates
      ('infiltrated'). Immunohistochemistry (IHC) was performed for four selected
      cytokines and chemokines to confirm and localize protein expression in human NP
      tissue samples. RESULTS: LDA identified the expression of numerous cytokine and
      chemokine associated genes including 15 novel cytokines and chemokines. Further q
      PCR gene expression studies identified differential expression patterns in NP
      cells derived from non-degenerate, degenerate and infiltrated IVDs. IHC confirmed
      NP cells as a source of IL-16, CCL2, CCL7 and CXCL8 and that protein expression
      of CCL2, CCL7 and CXCL8 increases concordant with histological degenerative
      tissue changes. CONCLUSIONS: Our data indicates that NP cells are a source of
      cytokines and chemokines within the IVD and that these expression patterns are
      altered in IVD pathology. These findings may be important for the correct
      assessment of the 'degenerate niche' prior to autologous or allogeneic cell
      transplantation for biological therapy of the degenerate IVD.

PMID- 24325990
TI  - Hypothyroidism and reversible kidney dysfunction: an essential relationship to
      recognize.
AB  - OBJECTIVE: To report 3 cases of reversible hypothyroidism-induced kidney
      dysfunction and review the interaction between these commonly encountered, yet
      seemingly disparate, conditions. METHODS: We describe the clinical course and
      laboratory and physical findings of 3 patients who presented with kidney
      dysfunction that improved after initiating thyroid hormone replacement therapy.
      We also review similar cases in the literature and discuss the pathophysiologic
      mechanisms. RESULTS: A 68-year-old male presented with classical signs and
      symptoms of hypothyroidism, including fatigue, confusion, and gait imbalance.
      Physical exam showed bradycardia, thyromegaly, slow mentation, and cracked, thin
      skin; he was found to have decreased kidney function. Second, a 42-year-old
      previously healthy female presented with bilateral hand swelling and elevated
      serum creatinine with an otherwise unremarkable physical exam. The third patient
      was a 72-year-old male with advanced heart failure on amiodarone and stage 3
      chronic kidney disease who presented with fatigue, acute kidney injury, and lower
      extremity edema. In all cases, serum creatinine and thyroid-stimulating hormone
      (TSH) were elevated at presentation (1.4-3.0 mg/dL and 94.1-184 mIU/L
      respectively), and free thyroxine (T4) was low (undetectable-0.4 ng/dL). The
      initiation or increased dose of levothyroxine normalized serum creatinine to
      baseline within 2 to 10 months. CONCLUSION: Hypothyroidism and kidney dysfunction
      are both commonly encountered clinical entities, but the interplay between the
      thyroid gland and kidneys may be infrequently recalled, causing the reversible
      relationship between these 2 disorders to be missed.

PMID- 24325989
TI  - Orthodontic-surgical treatment: neuromuscular evaluation in open and deep
      skeletal bite patients.
AB  - BACKGROUND: The aim of this study was to compare electromyographic data of two
      groups of patients (open and deep skeletal bite) before and after surgical
      orthodontic treatment. METHODS: All patients who underwent orthognathic surgery
      at the Department of Orthodontics (University of Milan) were subjected to
      periodic electromyographic evaluation of the masticatory muscles (masseter and
      anterior temporal muscles) and to electrokinesiographic evaluation of mandibular
      movements. The sample comprised 72 patients (35 open skeletal bite patients and
      37 deep skeletal bite patients) at the end of craniofacial growth. The
      electromyographic instruments used in the study included a Freely and a K6-I
      electromyograph. Statistical evaluation was carried out with Student's t tests
      for independent samples. RESULTS: Lots of differences between open and deep
      skeletal bite patients have been underlined by the analysis of the
      electromyographic data obtained. These results have been obtained with both
      electromyographic systems. Muscular activity in microvolts is higher in deep
      skeletal bite patients at the beginning of the treatment than in open bite ones,
      but during the following phases of the treatment, the two values became similar.
      CONCLUSIONS: Morphologic differences between open and deep bite patients can also
      be demonstrated by instrumental examinations, and their correction after surgical
      treatment is observable on electromyographic and electrognatographic exams.

PMID- 24325991
TI  - Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBDs): What the
      Endocrinologist Needs to Know.
AB  - OBJECTIVE: Chronic kidney disease-mineral and bone disorders (CKD-MBDs) are a
      spectrum of abnormalities involving skeletal hormones, minerals, and bone
      turnover and mineralization. This paper focuses on what the endocrinologist
      should know about the assessment and management of skeletal and metabolic
      disorders in CKD-MBDs. METHODS: Relevant literature was reviewed to (1) define
      disturbances of minerals and hormones in the course of CKD; (2) identify the
      variable radiographic and histomorphometric changes of CKD-MBDs; (3) review the
      association among CKD-MBDs, vascular calcification, cardiovascular disease (CVD),
      and mortality; and (4) clarify issues in CKD-MBDs therapy. RESULTS: Assessment
      and treatment of CKD-MBDs is complicated by progressive changes in bone minerals
      and skeletal regulatory hormones as kidney function declines. CKD-MBDs are
      associated with fracture risk, and studies demonstrate that bone mineral density
      can be used to assess bone loss and fracture risk in these patients. Treatment of
      CKD-MBDs continues to evolve. Use of calcium, phosphate binders, vitamin D,
      vitamin D-receptor analogs, and drugs for osteoporosis and CKD-MBDs treatment are
      discussed in the context of safety and efficacy for patients with CKD.
      CONCLUSION: The association of CKD with bone disease, vascular calcification,
      CVD, and mortality mandates earlier recognition and treatment of CKD-MBDs.
      Osteoporosis as a distinct entity can be diagnosed and managed in CKD, although
      assessment of osteoporosis becomes challenging in late (stage 4 to 5) CKD.
      Diabetes is common in early (stage 1 to 3) CKD. In addition, 96% of all
      individuals identified as having CKD have early CKD. The endocrinologist is
      uniquely positioned to address and treat both diabetes and many of the metabolic
      and skeletal disorders associated with early CKD-MBDs, including osteoporosis.

PMID- 24325992
TI  - Cushing's syndrome due to a corticotropin-releasing hormone- and
      adrenocorticotrophic hormone-producing neuroendocrine pancreatic tumor.
AB  - OBJECTIVE: To our knowledge, only 2 cases of pancreatic neuroendocrine tumors
      have been described as the source of corticotropin-releasing hormone (CRH) in
      Cushing's syndrome. Here, we describe a case of ectopic adrenocorticotrophic
      hormone (ACTH-) and CRH-production caused by a pancreatic neuroendocrine tumor.
      METHODS: We analyzed and summarized the patient's medical history, physical
      examination results, laboratory data, imaging studies, and histopathologic
      results. RESULTS: An endocrinologic workup revealed massive ACTH-dependent
      hypercortisolism. Pituitary magnetic resonance imaging (MRI) showed no pathologic
      findings and led to extensive imaging in search of the suspected ectopic lesion.
      Ketoconazole treatment was initiated. Rapid deterioration of the patient's
      clinical condition due to escalating cortisol levels and resulting sepsis
      required an emergency adrenalectomy to control the hypercortisolism. A positron
      emission tomography-computed tomography (PET-CT) scan revealed a hepatic lesion,
      which was biopsied. Histology of the lesion showed a well-differentiated
      endocrine tumor. Subsequent scintigraphy with octreotide (a somatostatin [SMS]
      analog) detected a pancreatic tumor, which was endosonographically confirmed. The
      initiated SMS therapy was followed by a distal splenopancreatectomy and a right
      hemihepatectomy. Immunostaining of the specimen showed positive expression for
      CRH and ACTH. CONCLUSION: We conclude that SMS-scintigraphy did have an
      additional diagnostic benefit compared to PET-CT. In hypercortisolemic patients,
      rapid endocrinologic evaluation is crucial to prevent rapid deterioration and a
      possible fatal outcome.

PMID- 24325993
TI  - Uterine volume and endometrial thickness in the early follicular phase in
      patients with polycystic ovary syndrome.
AB  - OBJECTIVE: We aimed to evaluate uterine volume and endometrial thickness during
      the early follicular phase in patients with polycystic ovary syndrome (PCOS) and
      healthy controls. METHODS: We studied 1,016 PCOS patients and 182 healthy
      controls. The anthropometric, endocrine, and metabolic characteristics of PCOS
      were determined. Uterine volume and endometrial thickness were also recorded.
      RESULTS: Uterine volume progressively increased with age both in PCOS patients
      and controls. Patients with PCOS and body mass index (BMI) >=25 kg/m2 had greater
      uterine volumes than PCOS patients with BMI <25 kg/m2 (P<.001). Patients with the
      classic PCOS phenotypes (i.e., with oligo-ovulation and/or anovulation [ANOV] and
      hyperandrogenemia [HA] with or without polycystic ovaries [PCO]) had smaller
      uterine volume than PCOS patients with the additional phenotypes introduced by
      the Rotterdam criteria (i.e., with PCO and either ANOV or HA; P = .033) and
      controls (P = .045). CONCLUSION: Uterine volume increases progressively with age
      and obesity in PCOS patients. The smaller uterine volumes and endometrial
      thicknesses in the classic PCOS phenotypes might be attributed to the more severe
      HA of these patients.

PMID- 24325994
TI  - Sentinel Lymph Node Biopsy Status Correlates with Postoperative Stimulated
      Thyroglobulin Levels in Low-risk Papillary Thyroid Cancer Patients.
AB  - OBJECTIVE: Radioactive iodine (RAI) remnant ablation in low-risk papillary
      thyroid cancer (PTC) is controversial. Current patient selection guidelines
      recommend the use of postoperative stimulated thyroglobulin (stim-Tg), neck
      dissections, and sonography but fail to include sentinel lymph node biopsy
      (SLNB). The objective of this study was to evaluate the correlation between SLNB
      status and postoperative stimulated thyroglobulin as a surrogate marker of
      clinical outcome. METHODS: Retrospective chart review of low-risk PTC patients
      who underwent a total thyroidectomy with SLNB at the McGill Thyroid Cancer
      Center. SLNBs were obtained using methylene blue dye. Biochemical measurements
      were acquired between 4 and 12 weeks postoperatively. Statistical analyses were
      performed using logistic regression models and receiver operating characterisitc
      (ROC) curves. A P-value <.05 was considered significant. RESULTS: Ninety-six
      patients were included in this study. The positive SLNB rate was 14.6%. The mean
      postoperative Tg level was 1.41 MUg/L. There were no significant correlations
      between the SLNB and the covariates analyzed (age, gender, histology, tumor size,
      and thyrotropin levels). Patients with negative SLNB were significantly more
      likely to have a lower stim-Tg (P<.0001). When postoperative Tg was analyzed as a
      categorical variable, a threshold of <1 MUg/L was significantly associated with a
      negative SLNB, with a sensitivity and specificity (determined by ROC curves) of
      0.86 and 0.88, respectively. CONCLUSION: There exists a correlation between SLNB
      and postoperative Tg. This creates the possibility of a new approach to RAI
      administration among low-risk PTC patients incorporating SLNB to the current
      guidelines.

PMID- 24325995
TI  - Preclinical atherosclerosis in patients with prolactinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of hyperprolactinemia
      on body fat, insulin sensitivity, inflammatory markers, and cardiovascular risk
      in patients with prolactinoma. METHODS: The study included 35 untreated
      hyperprolactinemic patients with pituitary adenomas, and 36 age-, gender-, and
      body mass index (BMI)-matched healthy controls without any known disease. Serum
      glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR,
      lipid profile, high-sensitivity C-reactive protein (hs-CRP), and heart-type fatty
      acid binding protein (H-FABP) levels were measured. Waist and hip circumference
      (WC and HC) were measured in all the participants. The body fat percentage was
      measured, and the visceral fat and abdominal fat percentages were measured via
      bioelectrical impedance (BIA). In addition, carotid intima media thickness (CIMT)
      was measured using high-resolution B-mode ultrasound. RESULTS: The serum glucose
      level, HOMA-IR, triglyceride level, and SC were significantly higher in the
      patient group than in the control group. The hs-CRP level and CIMT were
      significantly higher in the hyperprolactinemic patients. Visceral and truncal fat
      percentages were significantly higher in the patients with prolactinoma. H-FABP
      levels were similar in the 2 groups, and there was a positive correlation between
      the prolactin (PRL) and H-FABP protein levels. CONCLUSIONS: Based on the present
      findings, hyperprolactinemia is associated with preclinical atherosclerosis and
      metabolic abnormalities. Patients with hyperprolactinemia might experience
      cardiovascular disease in the long term. Metabolic control should be achieved in
      addition to the control of hyperprolactinemia in the clinical management of
      patients diagnosed with prolactinoma.

PMID- 24325996
TI  - Inpatient Management of Diabetes Mellitus among Noncritically Ill Patients at
      University Hospital of Puerto Rico.
AB  - OBJECTIVE: To describe the state of glycemic control in noncritically ill
      diabetic patients admitted to the Puerto Rico University Hospital and adherence
      to current standard of care guidelines for the treatment of diabetes. METHODS:
      This was a retrospective study of patients admitted to a general medicine ward
      with diabetes mellitus as a secondary diagnosis. Clinical data for the first 5
      days and the last 24 hours of hospitalization were analyzed. RESULTS: A total of
      147 noncritically ill diabetic patients were evaluated. The rates of
      hyperglycemia (blood glucose >=180 mg/dL) and hypoglycemia (blood glucose <70
      mg/dL) were 56.7 and 2.8%, respectively. Nearly 60% of patients were
      hyperglycemic during the first 24 hours of hospitalization (mean random blood
      glucose, 226.5 mg/dL), and 54.2% were hyperglycemic during the last 24 hours of
      hospitalization (mean random blood glucose, 196.51 mg/dL). The mean random last
      glucose value before discharge was 189.6 mg/dL. Most patients were treated with
      subcutaneous insulin, with basal insulin alone (60%) used as the most common
      regimen. The proportion of patients classified as uncontrolled receiving basal
      bolus therapy increased from 54.3% on day 1 to 60% on day 5, with 40% continuing
      to receive only basal insulin. Most of the uncontrolled patients had their
      insulin dose increased (70.1%); however, a substantial proportion had no change
      (23.7%) or even a decrease (6.2%) in their insulin dose. CONCLUSION: The
      management of hospitalized diabetic patients is suboptimal, probably due to
      clinical inertia, manifested by absence of appropriate modification of insulin
      regimen and intensification of dose in uncontrolled diabetic patients. A
      comprehensive educational diabetes management program, along with standardized
      insulin orders, should be implemented to improve the care of these patients.

PMID- 24325997
TI  - Efficacy and safety of insulin lispro in obese patients with type 2 diabetes: a
      retrospective metaanalysis of 7 randomized controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy and safety of insulin lispro in the treatment
      of patients with type 2 diabetes (T2DM) who had a body mass index (BMI) >=30
      kg/m2 (obese) compared with patients with BMIs <30 kg/m2 (nonobese). METHODS: A
      retrospective analysis of predefined end-points from 7 randomized clinical trials
      of T2DM patients treated with insulin lispro was performed. The primary efficacy
      measure was to assess the noninferiority of insulin lispro in obese patients
      versus nonobese patients as measured by the change in hemoglobin A1C (HbA1c) from
      baseline to Month 3 (n = 1,518), using a noninferiority margin of 0.4%. The
      secondary measures included overall hypoglycemia incidence and event rates and
      relative change in body weight. RESULTS: Mean changes in HbA1c from baseline
      (9.06% for obese and 8.92% for nonobese) to Month 3 were similar for obese
      patients (-1.03%) and nonobese (-1.02%), with a least squares (LS) mean
      difference (95% confidence interval [CI]) of -0.05% (-0.17%, 0.07%; P = .384).
      The overall incidence of hypoglycemia (53% vs. 63%; P<.001) and rate of
      hypoglycemia (0.93 vs. 1.76 events per 30 days; P<.001) was significantly lower
      in obese patients compared with nonobese patients. The 2 BMI cohorts did not
      demonstrate a significant difference in mean percent changes in body weights (LS
      mean difference = 0.4% [-0.2%, 0.9%]; P = .202). CONCLUSION: Obese patients with
      T2DM treated with insulin lispro were able to achieve the same level of glycemic
      control as their nonobese counterparts, with some evidence supporting a reduced
      risk of hypoglycemia.

PMID- 24325998
TI  - Pituitary apoplexy secondary to thrombocytopenia due to dengue hemorrhagic fever:
      a case report and review of the literature.
AB  - OBJECTIVE: To present a case of pituitary apoplexy secondary to thrombocytopenia
      associated with dengue hemorrhagic fever (DHF). METHODS: In this case study, we
      review the presentation, evaluation, diagnosis, and management of a case of
      pituitary apoplexy in the setting of DHF. We also searched the literature for
      cases of pituitary apoplexy associated with thrombocytopenia and review their
      clinical presentation, management, and outcome. RESULTS: A 53-year-old man
      presented with fever, lethargy, and worsening headache. Routine investigations
      revealed thrombocytopenia secondary to dengue fever. He developed symptoms of a
      cavernous sinus lesion the next day. Urgent magnetic resonance imaging revealed
      pituitary apoplexy in a pituitary macroadenoma. A transsphenoidal surgery was
      done and histology was consistent with apoplexy in a prolactin/follicle
      stimulating hormone macroadenoma. Subsequently, the patient developed permanent
      deficits of anterior pituitary hormones. We review 8 other cases of pituitary
      apoplexy associated with thrombocytopenia reported in the literature. CONCLUSION:
      Thrombocytopenia due to various causes may be a predisposing factor for pituitary
      apoplexy in a patient with underlying pituitary disease. In view of the tendency
      for bleeding associated with thrombocytopenia, the risks of surgical intervention
      have to be carefully weighed against the potential benefits. Indications for
      surgery would include progressive alteration of consciousness, visual
      disturbances, and opthalmoplegia despite conservative management. Patients with
      underlying pituitary macroadenomas with optic chiasm compression have a worse
      prognosis, and the chances of recovery, even with early surgery, are limited.

PMID- 24325999
TI  - Surgeons and patients disagree on the potential consequences from
      hypoparathyroidism.
AB  - OBJECTIVE: To test the hypothesis that surgeons and their patients underestimate
      the potential negative impact that permanent hypoparathyroidism has on quality of
      life (QOL). METHODS: We used a modified SF-36 assessment tool to compare the
      perceptions of patients with permanent hypoparathyroidism to the perceptions of
      control subjects who were given a standardized preoperative statement about the
      complications of hypoparathyroidism. We also elicited the perceptions of
      endocrine surgeons regarding the QOL impacts of hypoparathyroidism using a subset
      of questions from the modified SF-36. RESULTS: A total of 340 postsurgical
      patients with permanent hypoparathyroidism, 200 controls, and 102 surgeons
      participated in the study. Both surgeons and controls underestimated the negative
      impact of hypoparathyroidism on QOL when compared to patients living with
      permanent hypoparathyroidism. Forty-seven percent of hypoparathyroid patients
      believed that their health was "much worse" than before surgery, compared with
      16% of surgeons (P<.001) and 7% of controls (P<.001). Postoperative
      hypoparathyroid patients also reported far more negative effects on QOL, from
      interference with social activities, paresthesias, muscle cramping, and
      medications than were anticipated by surgeons or controls (P<.05 for all
      comparisons). In each of the 8 dimensions of QOL, including physical functioning,
      role limitations due to physical health, role limitations due to emotional
      problems, energy/fatigue, emotional well-being, social functioning, pain, and
      general health, hypoparathyroid patients reported a significantly lower mean
      score compared to the control group (P<.001 for all comparisons). CONCLUSION: The
      impact of postoperative hypoparathyroidism on patient QOL is consistently and
      significantly underestimated by surgeons and subjects receiving surgical
      consultation.

PMID- 24326000
TI  - Comparison of radioiodine utilization in adolescent and young adult and older
      thyroid cancer patients.
AB  - OBJECTIVE: Differentiated thyroid cancer (DTC) is 1 of the most common cancers in
      adolescents and young adults (AYA, ages 15-39). Although most AYAs with DTC are
      considered low risk compared to older patients, there are no specific
      postoperative radioiodine (RAI) treatment recommendations despite the potential
      adverse effects specific to this age group, namely secondary malignancies and
      fertility difficulties. This study compares factors influencing RAI utilization
      in AYA and older patients. METHODS: A total of 5,687 primary DTC patients were
      identified from the SEER (Surveillance, Epidemiology, and End RESULTS) database
      between January 1, 2004 and January 31, 2009. The 2009 American Thyroid
      Association (ATA) guidelines were used to classify patients as low (LR) or
      intermediate/high risk (IHR) based on tumor characteristics. Multivariate
      logistic regression analysis was performed. RESULTS: Overall, 56.9% of AYA (n =
      1,963) patients received postoperative RAI compared to 52.2% of older (n = 3,724)
      patients (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.09-1.35, P =
      .001). For AYA patients, having a total thyroidectomy (TTx) (OR: 3.53, 95% CI:
      2.7-4.61, P<.001) predicted RAI in a multivariate model whereas LR status (OR:
      0.52, 95% CI: 0.43-0.63, P<.001) and northeast residence (OR: 0.39, 95% CI: 0.29
      0.52, P<.001) decreased the probability. All 3 factors similarly affected older
      patients in addition to an increased likelihood after lymph node (LN) dissection.
      Additionally, after selecting for TTx (n = 1,077), no factor influenced the use
      of RAI for AYA patients, whereas LR (OR: 0.30, 95% CI: 0.21-0.43, P<.001) and
      northeast residence (OR: 0.39, 95% CI: 0.19-0.79, P = .008) were associated with
      decreased RAI use in older patients. CONCLUSION: Despite their excellent
      prognosis, AYA thyroid cancer patients are more likely to receive postoperative
      RAI compared to older patients. Increased awareness of the unique survivorship
      implications for AYA patients will be an important aspect to address going
      forward.

PMID- 24326001
TI  - Examination of implementation of intravenous and subcutaneous insulin protocols
      and glycemic control in heart transplant patients.
AB  - OBJECTIVE: Perioperative glycemic management is particularly challenging in heart
      transplant (HT) patients who are on high-dose steroids and subject to surgical
      stress. The objective of the study was to examine the efficacy and safety of
      perioperative insulin administration in HT patients with and without diabetes.
      METHODS: Medical records of 71 HT patients from June 1, 2005 to July 31, 2009
      whose hyperglycemia was managed by our Glucose Management Service (GMS) were
      analyzed for up to 1 year after HT. Their daily blood glucose (BG) averages on
      intravenous (i.v.) insulin drips and subcutaneous (s.q.) insulin, hypoglycemia
      rates, reasons for hypoglycemia, and deviations from insulin protocols were
      analyzed. RESULTS: Daily BG averages between diabetic (DM) and nondiabetic
      (nonDM) patients were not significantly different while on the drip but were
      significantly different for first 5 days on s.q. (P<.05). The daily insulin
      glargine doses were similar. No patients developed severe hypoglycemia (BG <=40
      mg/dL) while on drip, and only 2.8% experienced hypoglycemia on s.q. Among 40
      episodes of moderate hypoglycemia while on drip, 15 had nurse deviations from
      protocol prior to the episode. Posttransition day fasting glucose was at goal
      (mean 124.7 +/- 35.4 mg/dL); however 39.4% (28/71) of patients received a
      transition insulin glargine dose that was different from the amount indicated by
      protocol. The likelihood of developing moderate hypoglycemia on s.q. was
      associated with the glargine dose used at the time of transition (odds ratio [OR]
      1.03, P = .034). CONCLUSION: Inpatient insulin protocols implemented by a GMS are
      successful in obtaining glycemic control with minimal side effects in patients
      with and without diabetes, even when they are on a high-dose steroid regimen.

PMID- 24326002
TI  - Evaluation of Variables Influencing the Measurement of Insulin-like Growth Factor
      1.
AB  - OBJECTIVE: Our aim was to identify the frequency and possible clinical and
      analytical factors leading to "falsely" elevated insulin-like growth factor-1
      (IGF-1). METHODS: We performed a retrospective review of patients with IGF-1
      concentrations above the reference interval. They were selected from a database
      of patients who had consecutive IGF-1 measurements between the years 2007-2010.
      RESULTS: Out of 2,747 unique patients, 117 (4%) were found to have IGF-1
      concentrations above the reference interval that were considered false-positives
      following a review of the clinical data. There was no relationship between the
      percentage of increase in IGF-1 and age, sex, body mass index (BMI),
      comorbidities, medication use, gonadal status, baseline growth hormone (GH), or
      insulin-like growth factor binding protein-3 (IGFBP-3) concentrations. An
      abnormal IGF-1 concentration led to performance of an oral glucose tolerance test
      (OGTT) for GH suppression in 21 of 117 patients (18%) and repeat IGF-1
      measurements in 52 patients (44%). In 34 of 52 patients (65%) with a median
      follow-up of 36 months, the subsequent IGF-1 concentration was within the
      reference interval. CONCLUSION: Discovery of "falsely" elevated IGF-1
      concentrations may lead to unnecessary testing and physician visits. Although the
      cause of the "falsely" elevated IGF-1 concentrations during the study period
      remains to be elucidated, it appears they are caused by a combination of high
      biological variability and method-specific assay performance issues. Clinicians
      should consider retesting patients with potentially spurious IGF-1 elevations
      after some time interval before embarking on more extensive investigations.

PMID- 24326003
TI  - Efficacy and Safety of Linagliptin in Black/African American Patients with Type 2
      Diabetes: A 6-month, Randomized, Double-blind, Placebo-controlled Study.
AB  - OBJECTIVE: Although black/African American individuals are disproportionately
      affected by type 2 diabetes, there is scant clinical trial information available
      on antidiabetes therapies in this group. We compared linagliptin with placebo in
      black/African American adults who were treatment-naive or receiving one oral
      antidiabetes drug. METHODS: Of 226 patients randomized to 24 weeks' linagliptin 5
      mg/day or placebo, 208 had baseline and at least one on-treatment glycated
      hemoglobin (HbA1c) measurement. Mean baseline HbA1c was 8.6% in the linagliptin
      group (n = 98) and 8.68% in the placebo group (n = 110). The primary outcome was
      change in HbA1c from baseline to week 24. RESULTS: By week 24, mean HbA1c changes
      were -0.84% with linagliptin and -0.25% with placebo (treatment difference, 
      0.58%; P<.001), and more patients in the linagliptin group achieved HbA1c <7.0%
      (26.8% vs. 8.3%; P = .001) or an HbA1c reduction >=0.5% (54.1% vs. 30.0%;
      P<.001). Mean weight loss was -1.1 kg in both groups. During the treatment
      period, 8 of 98 linagliptin-group patients and 17 of 110 placebo-group patients
      required rescue therapy (odds ratio, 0.5; P = .14). For postprandial glucose,
      values were available for few patients (11 placebo, 10 linagliptin), and thus the
      between-group difference was associated with wide confidence intervals (CIs)
      (difference, -1.97 mg/dL; 95% CI, -53.80 to 49.86; P = .94). In the overall study
      population, a similar proportion of patients in both groups had adverse events
      (58.5% vs. 61.7%); most events were mild or moderate and considered unrelated to
      study drug. Investigator-defined hypoglycemia was rare (3 linagliptin-group
      patients and 1 placebo-group patient), with no severe events (requiring external
      assistance). CONCLUSION: This study confirms that linagliptin is efficacious and
      well tolerated in black/African American patients with type 2 diabetes.

PMID- 24326004
TI  - Effect of glargine insulin delivery method (pen device versus vial/syringe) on
      glycemic control and patient preferences in patients with type 1 and type 2
      diabetes.
AB  - OBJECTIVE: To evaluate the effects of two different glargine insulin delivery
      methods (pen device vs. vial/syringe) on glycemic control and patient preferences
      in a randomized, open-label, crossover, comparative effectiveness study. METHODS:
      Thirty-one patients discharged from the hospital were recruited for this study.
      In the hospital, all patients were treated with a basal-bolus insulin regimen.
      Upon discharge, 21 patients received glargine by pen device for 3 months and were
      then switched to vial/syringe for the next 3 months (group 1). Group 2 consisted
      of 10 patients discharged on vial/syringe and converted to pen device after 3
      months. Hemoglobin A1c (HbA1c) was measured at enrollment and at 3 and 6 months.
      A questionnaire assessing patient preference was administered at 3 and 6 months.
      RESULTS: Groups 1 and 2 had similar baseline HbA1c (10.7 +/- 2.2% and 11.2 +/-
      2.5%, respectively) and similar reduction in HbA1c at 3 months (7.8 +/- 1.7% and
      7.3 +/- 1.4%, respectively; P<.001 vs. baseline). However, after crossover, the
      changes in HbA1c from 3 to 6 months were significantly different between groups.
      HbA1c increased to 8.5 +/- 2.0% at 6 months in group 1 after switching to the
      vial/syringe but remained unchanged (7.1 +/- 1.6%) in group 2 after switching to
      a pen device (P<.01, group 1 vs. group 2). Patient questionnaires after each
      phase of the trial revealed that patients found the pen device more convenient
      and were more likely to recommend this insulin delivery method to someone else.
      CONCLUSION: Patients switching to a glargine pen device achieved lower HbA1c at
      the 6-month follow-up. Patients in both groups overwhelmingly preferred glargine
      pens over vials/syringes.

PMID- 24326005
TI  - Visual vignette.

PMID- 24326006
TI  - Amelioration of experimental arthritis by stroke-induced immunosuppression is
      independent of Treg cell function.
AB  - OBJECTIVES: Clinical evidence suggests that neurological lesions can protect from
      arthritis. Acute cerebral ischaemia induces severe immunosuppression, resulting
      in enhanced susceptibility to infections. We aimed to determine if stroke-induced
      immunosuppression can ameliorate arthritis and to delineate the immunological
      mechanisms involved. METHODS: Unilateral cerebral ischaemia was induced in mice
      by occlusion of one middle cerebral artery (MCAO) at different time points after
      induction of G6PI-induced arthritis in mice. Clinical and histological signs of
      arthritis were assessed. Regulatory T cells were specifically depleted by
      injection of diphtheria toxin into transgenic DEREG mice. Immunological
      correlates of MCAO were determined by flow cytometry and serological methods.
      RESULTS: MCAO reduced the clinical and histological signs of arthritis
      significantly. To be effective, stroke had to be induced during the induction
      phase or the early clinical stage of arthritis. MCAO induced a global loss of
      leucocytes. Despite the reduced absolute number of lymphocytes, the functional
      differentiation of T helper cells into Th1/17 cells and the production of
      autoantibodies were unimpaired. Depletion experiments showed that regulatory T
      cells were dispensable for the protective effect of MCAO. CONCLUSIONS: MCAO
      ameliorates arthritis. The correlate of protection from arthritis is not the
      reduction of a particular pathogenic leucocyte subset or the preferential
      expansion or emergence of a protective cell population but the global reduction
      of leucocytes during arthritis.

PMID- 24326007
TI  - High-density lipoproteins inhibit urate crystal-induced inflammation in mice.
AB  - OBJECTIVES: To investigate the effects and mechanisms of action of high-density
      lipoproteins (HDL) in monosodium urate (MSU) crystal-induced inflammation -that
      is, gouty inflammation, in vivo. METHODS: Air pouches raised on the backs of mice
      were injected with MSU crystals or tumour necrosis factor (TNF) in the presence
      or absence of HDL and/or interleukin (IL)-1 receptor antagonist (IL-1Ra) for 3 h.
      Leucocyte count and neutrophil percentage in pouch fluids were measured using a
      haemocytometer and May-Grunwald-Giemsa staining. The cytokine production and
      expression in the pouch were measured by ELISA and quantitative RT-PCR. RESULTS:
      MSU crystals induced leucocyte infiltration, mostly neutrophils, and the release
      of IL-1beta, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C
      motif) ligand 2 (CCL2) and IL-1Ra in pouch fluids. TNF remained under the
      detection limit. MSU crystals triggered IL-1beta, IL-6 and CXCL1 expression in
      both pouch exudates and membranes, whereas CCL2 and TNF mRNA were not modulated.
      The co-injection of MSU crystals and HDL inhibited leucocyte influx by 59% and
      neutrophil infiltration by 83% and, in turn, both protein and mRNA levels of all
      assessed proinflammatory cytokines were reduced, but not those of IL-1Ra. Similar
      results were obtained when mice were injected with MSU crystals pretreated with
      HDL or TNF instead of crystals. When HDL and IL-1Ra were added together they
      displayed additional inhibition, suggesting different mechanisms of action.
      CONCLUSIONS: This study demonstrated that HDL may represent an important factor
      in the modulation of gouty inflammation by acting on both tissue and infiltrating
      cells -that is, synovial tissue and synovial fluid cells. HDL display anti
      inflammatory activity, in part, by interacting with crystals but also by directly
      acting on cells.

PMID- 24326008
TI  - Key findings towards optimising adalimumab treatment: the concentration-effect
      curve.
AB  - OBJECTIVE: To determine a concentration-effect curve of adalimumab in rheumatoid
      arthritis (RA) patients taking into account the effect of methotrexate (MTX) on
      concentration and effect and to identify a therapeutic range for adalimumab
      concentrations. METHODS: In a prospective observational cohort study, 221
      consecutive patients with RA were treated with 40 mg adalimumab subcutaneously
      every other week. The relationship between adalimumab trough level and clinical
      efficacy after 28 weeks of follow-up was determined in a concentration-effect
      curve. A receiver-operator characteristics (ROC) curve established a therapeutic
      cut-off concentration. The effect of MTX on adalimumab trough levels was shown by
      dividing patients that are and are not concomitantly using MTX in the
      concentration-effect curve and a concentration table. RESULTS: Clinical efficacy
      improved with increasing adalimumab concentration and reached a maximum (mean
      disease activity score in 28 joints improvement of 2) with levels between 5-8
      MUg/mL. Levels exceeding 8 MUg/mL were illustrated to have no additional
      beneficial effect on disease activity. The ROC curve showed an area under the
      curve of 0.695 (95% CI 0.626 to 0.764) for European League Against Rheumatism
      response and adalimumab levels: good responders versus non-responders and
      moderate responders. A cut-off of 5 MUg/mL had a sensitivity of 91% and a
      specificity of 43%. Adalimumab levels are influenced by concomitant MTX use:
      patients on adalimumab monotherapy had a median adalimumab level of 4.1 MUg/mL
      (IQR 1.3-7.7), whereas patients concomitantly taking MTX had a median level of
      7.4 MUg/mL (IQR 5.3-10.6, p<0.001). CONCLUSIONS: Adalimumab trough levels in a
      range of 5-8 MUg/mL are sufficient to reach adequate clinical response. These
      levels are influenced substantially by concomitant MTX use.

PMID- 24326010
TI  - FUT2: filling the gap between genes and environment in Behcet's disease?
AB  - OBJECTIVES: To identify new susceptibility loci for Behcet's disease (BD), we
      performed a genome-wide association study (GWAS) using DNA pooling. METHODS: Two
      replicate pools of 292 Iranian BD cases and of 294 age- and sex-matched controls
      were allelotyped in quadruplicate on the Affymetrix Genome-Wide Human SNP Array
      6.0. Of the 51 top markers, 47 were technically validated through individually
      genotyping. Replication of validated single nucleotide polymorphisms (SNPs) was
      performed in an independent Iranian dataset (684 cases and 532 controls).
      RESULTS: In addition to the well-established HLA-B locus, rs7528842 in a gene
      desert on chromosome 1p21.2, and rs632111 at the 3'UTR of FUT2 were associated in
      both the discovery and replication datasets (individually and in combination).
      However, only the FUT2 SNP was associated in a previous GWAS for BD in Turkish
      people. Fine-mapping of FUT2 in the full Iranian dataset showed additional
      associations in five coding SNPs (2.97E-06<pcombined<1.34E-04), including the
      rs601338 nonsense (W143X) variant which, in Caucasians, determines the secretion
      of the H antigen (precursor of the ABO blood group antigens) in body fluids and
      on the intestinal mucosa. Meta-analysis with the published Turkish GWAS data
      strengthened the FUT2 associations (4.78E-09<pmeta<1.66E-07). CONCLUSIONS: This
      study suggests for the first time a putative link between a specific gene and
      environment in the aetiopathogenesis of BD. The non-secretor phenotype affects
      mucosal glycosylation, which may explain its known association with dysbiosis and
      altered susceptibility to infections. A different antigenic stimulation in early
      life and consequent increased propensity for autoimmunity and inflammation may
      contribute to BD development.

PMID- 24326009
TI  - Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by
      different phenotypes of cryopyrin-associated periodic syndromes.
AB  - : Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and
      chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are
      dominantly inherited autoinflammatory diseases associated to gain-of-function
      NLRP3 mutations and included in the cryopyrin-associated periodic syndromes
      (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ~35% of
      patients with CINCA. However, no data are currently available regarding the
      relevance of this mechanism in other CAPS phenotypes. OBJECTIVE: To evaluate
      somatic NLRP3 mosaicism as the disease-causing mechanism in patients with
      clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. METHODS:
      NLRP3 analyses were performed by Sanger sequencing and by massively parallel
      sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)
      dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF
      kappaB) activation and transfection-induced THP-1 cell death assays determined
      the functional consequences of the detected variants. RESULTS: A variable degree
      (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled
      patients, all of them with a MWS phenotype. Six different missense variants,
      three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and
      functional analyses confirmed that they were disease-causing, gain-of-function
      NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long
      lasting positive responses. CONCLUSIONS: We herein show somatic NLRP3 mosaicism
      underlying MWS, probably representing a shared genetic mechanism in CAPS not
      restricted to CINCA syndrome. The data here described allowed definitive
      diagnoses of these patients, which had serious implications for gaining access to
      anti-interleukin 1 treatments under legal indication and for genetic counselling.
      The detection of somatic mosaicism is difficult when using conventional methods.
      Potential candidates should benefit from the use of modern genetic tools.

PMID- 24326011
TI  - Immunogenicity, adalimumab levels and clinical response in ankylosing spondylitis
      patients during 24 weeks of follow-up.
AB  - BACKGROUND: Immunogenicity influences adalimumab levels and therefore clinical
      response in patients with rheumatic diseases. OBJECTIVES: To study the
      relationship between clinical response, adalimumab levels and antidrug antibodies
      (ADAb) in ankylosing spondylitis (AS). METHODS: Observational cohort study of 115
      consecutive AS patients treated with adalimumab in the Netherlands (n=85) and
      Taiwan (n=30), monitored during 24 weeks. Adalimumab levels and ADAb titres were
      determined using an ELISA and an antigen binding test (ABT), respectively,
      designed by Sanquin Research, Amsterdam. Response to adalimumab treatment was
      defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
      response, and disease activity was measured using the Ankylosing Spondylitis
      Disease Activity Score using C-reactive protein (CRP) (ASDAS). RESULTS: At
      baseline, median BASDAI (IQR) was 6.4 (4.5-7.6) and mean ASDAS (SD) was 3.5
      (1.0). After 24 weeks, 49 (42.6%) patients were BASDAI50 responders and mean
      ASDAS (SD) for responders was 1.5 (1.0) vs 2.6 (1.0) for non-responders
      (p<0.001). Thirty-one (27.0%) patients had detectable ADAb. After 24 weeks,
      adalimumab levels (mg/L) (IQR) were significantly higher in ADAb-negative
      patients than in ADAb-positive patients (12.7 (8.2-18.0) vs 1.2 (0.0-2.0),
      (p<0.001)). A significant association was demonstrated between adalimumab levels
      and ASDAS (p=0.02; RC -1.1; 95% CI -2.0 to -0.2). Eleven (9.6%) patients had no
      detectable adalimumab levels and high detectable ADAb titres (>100 AU/mL). In
      these patients, CRP and erythrocyte sedimentation rate remained elevated during
      treatment. CONCLUSIONS: Adalimumab levels are related to clinical response in AS
      patients measured with ASDAS and are influenced by ADAb detectable with an ABT.

PMID- 24326012
TI  - Response to: 'Five Factor Score in patients with eosinophilic granulomatosis with
      polyangiitis (Churg-Strauss; EGPA): to use or not to use?' by Moiseev and
      Novikov.

PMID- 24326013
TI  - Comparison of survival time between two types of orthodontic fixed retainer: a
      prospective randomized clinical trial.
AB  - BACKGROUND: The aim of this prospective clinical study was to compare the mean
      durability and the failure rates of two types of orthodontic retainers. METHODS:
      Orthodontic patients (142) aged between 14 and 28 years were recruited in this
      study. The polyethylene woven ribbon (Ribbond, Seattle, WA, USA) retainer was
      compared with a 0.0175-in flexible spiral wire (Respond, Ormco, Glendora, CA,
      USA) retainer. When treatment was completed, the retainers were bonded from
      canine to canine in the maxillary and the mandibular arches of the participants.
      In the follow-up visits, the patients were re-evaluated every 3 months over a
      period of 18 months. The time taken for the retainers to remain without any
      fracture was appraised. Kaplan-Meier analysis and the logrank test were employed
      to identify significant differences in the survival functions between the groups.
      The rates of the retainers' failure between the groups were analyzed using Chi
      square test. RESULTS: It was revealed that the mean survival of the flexible
      spiral wire retainer was 15.34+/-0.47 and 15.60+/-0.42 months in the maxillary
      and mandibular arches, respectively. The mean survival of the ribbon retainer was
      13.95+/-0.55 and 14.26+/-0.57 months in the maxillary and mandibular arches,
      respectively. Ribbon retainers showed a failure rate of 50% in the maxillary and
      42.6% in the mandibular arches. Flexible spiral retainers showed a failure rate
      of 36.5% in the maxillary and 37.8% in the mandibular arches. The differences
      were not statistically significant. Regarding the evaluation period, the
      differences had limited clinical significance. CONCLUSION: The mean survival time
      and the failure rates of the polyethylene woven ribbon retainer were comparable
      to the flexible spiral wire retainer during the 18 months after orthodontic
      treatment.

PMID- 24326014
TI  - Strain-dependent effects of prenatal maternal immune activation on anxiety- and
      depression-like behaviors in offspring.
AB  - There is converging evidence that prenatal maternal infection can increase the
      risk of occurrence of neuropsychiatric disorders like schizophrenia, autism,
      anxiety and depression in later life. Experimental studies have shown conflicting
      effects of prenatal maternal immune activation on anxiety-like behavior and
      hypothalamic-pituitary-adrenal (HPA) axis development in offspring. We
      investigated the effects of maternal immune activation during pregnancy on
      anxiety- and depression-like behaviors in pregnant mice and their offspring to
      determine whether these effects are dependent on strain. NMRI and C57BL/6
      pregnant mice were treated with either saline or lipopolysaccharide on
      gestational day 17 and then interleukin (IL)-6 and corticosterone (COR) levels;
      anxiety or depression in the pregnant mice and their offspring were evaluated.
      The results indicate that maternal inflammation increased the levels of COR and
      anxiety-like behavior in NMRI pregnant mice, but not in C57BL/6 dams. Our data
      also demonstrate that maternal inflammation elevated the levels of anxiety-and
      depression-like behaviors in NMRI offspring on the elevated plus-maze, elevated
      zero-maze, tail suspension test and forced swimming test respectively, but not in
      the open field and light-dark box. In addition, we did not find any significant
      change in anxiety- and depression-like behaviors of adult C57BL/6 offspring. Our
      findings suggest that prenatal maternal immune activation can alter the HPA axis
      activity, anxiety- and depression-like behaviors in a strain- and task-dependent
      manner in offspring and further comprehensive studies are needed to prove the
      causal relationship between the findings found here and to validate their
      relevance to neuropsychiatric disorders in humans. 

PMID- 24326015
TI  - Cancer immunotherapy: are we there yet?
AB  - The immune system is the built-in host defense mechanism against infectious
      agents as well as cancer. Protective immunity against cancer was convincingly
      demonstrated in the 1940s with syngeneic animal models (JNCI 18:769-778, 1976;
      Cancer Immun 1:6, 2001). Since then, the last century's dream has been to
      effectively prevent and cure cancers by immunological means. This dream has
      slowly but surely become a reality (Nature 480:480-489, 2011). The successful
      examples of immunoprophylaxis and therapy against cancers include: (i) targeted
      therapy using monoclonal antibodies (Nat Rev Cancer 12:278-287, 2012); (ii)
      allogeneic hematopoietic stem cell transplantion to elicit graft-versus-cancer
      effect against a variety of hematopoietic malignancies (Blood 112:4371-4383,
      2008); (iii) vaccination for preventing cancers with clear viral etiology such as
      hepatocellular carcinoma and cervical cancer (Cancer J Clin 57:7-28, 2007; NEJM
      336:1855-1859, 1997); (iv) T cell checkpoint blockade against inhibitory pathways
      including targeting CTLA-4 and PD-1 inhibitory molecules for the treatment of
      melanoma and other solid tumors (NEJM 363:711-723, 2010; NEJM 366:2443-2454,
      2012; NEJM 369:122-133, 2013; NEJM 366:2455-2465, 2012); (v) antigen-pulsed
      autologous dendritic cell vaccination against prostate cancer (NEJM 363:411-422,
      2010); and (vi) the transfer of T cells including those genetically engineered
      with chimeric antigen receptors allowing targeting of B cell neoplasms (NEJM
      365:725-733, 2011; NEJM 368:1509-1518, 2013; Blood 118:4817-4828, 2013; Sci
      Transl Med 5:177ra138, 2013).This article provides an overview on the exciting
      and expanding immunological arsenals against cancer, and discusses critical
      remaining unanswered questions of cancer immunology. The inherent specificity and
      memory of the adaptive immune response towards cancer will undoubtedly propel
      cancer immunotherapy to the forefront of cancer treatment in the immediate near
      future. Study of the fundamental mechanisms of the immune evasion of cancer shall
      also advance the field of immunology towards the development of effective
      immunotherapeutics against a wide spectrum of human diseases. 

PMID- 24326016
TI  - How safe is your motorcycle helmet?
AB  - PURPOSE: Motorcycle crash helmets do not totally prevent head and facial trauma.
      The aim of this study was to investigate if protection offered by helmets differs
      according to helmet type. MATERIALS AND METHODS: In this retrospective cohort
      study, outpatient records of motorcyclists were analyzed for the Facial Injury
      Severity Scale (FISS), traumatic brain injury (TBI), facial fractures, and helmet
      use. Statistical analysis was conducted using the Fisher and Bonferroni tests,
      bivariate regression analysis, and 1-way analysis of variance. RESULTS: There
      were 253 motorcyclists who sustained craniomaxillofacial injuries and were
      referred for outpatient treatment (men, 88.9%; mean age, 29.64 +/- 11.6 yr);
      60.1% had up to 9 years of formal education; 156 patients reported not using
      crash helmets, 51 were using open-face helmets, and 46 were using full-face
      helmets. The mean FISS score was significantly higher for unhelmeted riders
      compared with full-face helmet riders (P = .047), with no difference between
      unhelmeted riders and open-face helmet users (P = 1.00). Results for TBI were
      statistically greater for those wearing open-face helmets compared with full-face
      helmets (P = .035). CONCLUSION: In this study, a large percentage of
      motorcyclists had facial fractures and TBI, and crash helmets did not always
      offer adequate protection against craniomaxillofacial injury, especially open
      face helmets. Thus, further investigation into helmet types and quality of
      protection offered is recommended.

PMID- 24326017
TI  - Surgical treatment of excessive gingival display using lip repositioning
      technique and laser gingivectomy as an alternative to orthognathic surgery.
AB  - Excessive gingival display (EGD) is a condition in which an overexposure of the
      maxillary gingiva (>3 mm) is present during smiling. The proper diagnosis and
      determination of its etiology are essential for the selection of the right
      treatment modality. Different techniques have been used in cases of hyperactive
      upper lip: botulinum toxin injections, lip elongations with rhinoplasties, lip
      muscle detachments, myotomies, and lip repositions. This report presents a case
      of a young woman with an EGD larger than 10 mm during smiling caused by altered
      passive eruption, vertical maxillary excess, and a hyperactive upper lip that was
      treated with a modified lip repositioning technique and laser gingivectomy
      because she strongly refused orthognathic surgical treatment. A novel addition to
      the technique is proposed, a reversible trial accomplished just by applying
      sutures on the borders of the future split-thickness flap, marked using diode
      laser, before starting the flap incision.

PMID- 24326018
TI  - Is the lingual fracture line influenced by the mandibular canal or the mylohyoid
      groove during a bilateral sagittal split osteotomy? A human cadaveric study.
AB  - PURPOSE: Although the bilateral sagittal split osteotomy (BSSO) is a routinely
      performed procedure, exact control of the lingual fracture line remains
      problematic. The purpose of this study was to determine the various lingual
      splitting patterns in cadaveric human mandibles after a BSSO and the possible
      influence of the mandibular canal and mylohyoid groove on the lingual fracture
      line. MATERIALS AND METHODS: The investigators designed and implemented a case
      series to compare different lingual fracture lines. A standardized SSO was
      performed on 40 cadaveric hemimandibles using elevators and splitting forceps.
      The primary outcome variable during this study was the lingual fracture pattern
      possibly influenced by independent variables: the mandibular canal, the mylohyoid
      groove, and dental status. Descriptive and analytic statistics were computed for
      each study variable. RESULTS: Most lingual fractures (72.5%) ended in the
      mandibular foramen. Only 25% of fractures were "true" Hunsuck fractures, and no
      "bad splits" occurred. In addition, 35% of lingual fractures ran more than
      halfway or entirely through the mandibular canal, whereas only 30% of fractures
      ran along the mylohyoid groove. However, when the lingual fracture ran along this
      groove, it had a 6-fold greater chance of ending in the mandibular foramen.
      CONCLUSIONS: The hypothesis that the mandibular canal or mylohyoid groove would
      function as the path of least resistance was only partly confirmed. The use of
      splitters and separators did not increase the incidence of bad splits compared
      with the literature.

PMID- 24326019
TI  - Ultrasound endoscopic bone cutting for rapid maxillary expansion.
AB  - PURPOSE: This study evaluated the feasibility and morbidity of ultrasound
      endoscopic rapid maxillary expansion. PATIENTS AND METHODS: Thirteen consecutive
      patients (7 women and 6 men; mean age at time of surgery, 22 yr 10 months; range,
      15 yr 4 months to 26 yr 3 months) who required surgically assisted rapid palatal
      expansion were included in this study. Eight patients had Class III malocclusion
      and 5 had Class II malocclusion. All osteotomies were performed using ultrasound
      bone-cutting instruments under direct visualization with a rigid 30 degrees  2.7
      mm-diameter endoscope connected to a video system, with access through 3 small
      vertical incisions. RESULTS: Satisfactory maxillary expansion was achieved in all
      patients, with minimal postsurgical sequelae. The average operative time for the
      13 cases was 74 minutes (standard deviation, 11 minutes) and was not dependent on
      the quality of bone. Postoperative pain was measured using a visual analog scale
      ranging from 0 to 10 and was found to be 1.5 +/- 0.8 on the first postoperative
      day, which decreased to 0.9 +/- 0.4 on the second day. Mucosal healing was
      excellent and none of the patients had excessive edema, hematoma formation, or
      nerve injury. CONCLUSION: The procedure described is minimally invasive and has
      advantages over the usual technique in providing direct vision, creation of a
      precise and safe osteotomy, minimal bleeding risk, and decreased dissection.

PMID- 24326020
TI  - Modeling anaerobic digestion of blue algae: stoichiometric coefficients of amino
      acids acidogenesis and thermodynamics analysis.
AB  - In order to facilitate the application of Anaerobic Digestion Model No. 1 (ADM1),
      an approach for a detailed calculation of stoichiometric coefficients for amino
      acids acidogenesis during the anaerobic digestion of blue algae is presented. The
      simulation results obtained support the approach by good predictions of the
      dynamic behavior of cumulative methane production, pH values as well as the
      concentrations of acetate, propionate, butyrate, valerate and inorganic nitrogen.
      The sensitivity analysis based on Monte Carlo simulation showed that the
      stoichiometric coefficients for amino acids acidogenesis had high sensitivities
      to the outputs of the model. The model further indicated that the Gibbs free
      energies from the uptake of long-chain fatty acids (LCFA), valerate and butyrate
      were positive through the digestion, while the free energies for other components
      were negative. During the digestion, the cumulative heat productions from
      microbial activities and methane were 77.69 kJ and 185.76 kJ, respectively. This
      result suggested that proper heat preservation of anaerobic digesters could
      minimize the external heating needs due to the heat produced from microbial
      activities.

PMID- 24326021
TI  - The role of iron in sulfide induced corrosion of sewer concrete.
AB  - The sulfide-induced corrosion of concrete sewer is a widespread and expensive
      problem for water utilities worldwide. Fundamental knowledge of the initiation
      and propagation of sewer corrosion, especially the interactions between chemical
      reactions and physical structure changes, is still largely unknown. Advanced
      mineral analytical techniques were applied to identify the distribution of
      corrosion products and the micro-cracking that developed along the corrosion
      boundary. It was found that sewer concrete corrosion caused by reactions with
      sulfuric acid progressed uniformly in the cement of concrete. In contrast to
      conventional knowledge, iron rust rather than gypsum and ettringite was likely
      the factor responsible for cracking ahead of the corrosion front. The analysis
      also allowed quantitative determination of the major corrosion products, i.e.,
      gypsum and ettringite, with the latter found closer to the corrosion front. The
      conceptual model based on these findings clearly demonstrated the complex
      interactions among different chemical reactions, diffusion, and micro-structure
      changes. 

PMID- 24326022
TI  - Modeling the pH effect on sulfidogenesis in anaerobic sewer biofilm.
AB  - Wastewater pH affects the transfer of H2S from liquid to gas and hence impacts on
      the extent of odour and corrosion. Sewage pH may change significantly in sewer
      networks due to, for example, the fermentation of organic compounds, particularly
      when the hydraulic retention time is long, the discharge of trade wastes that are
      organic-rich or with extreme pH, and the intentional addition of alkali to raise
      the sewage pH. Such a variation of pH is expected to affect sulfate reduction by
      sewer biofilms. In this work, experimental studies were carried out to reveal the
      detailed effects of pH on sulfidogenesis by anaerobic sewer biofilms developed in
      a laboratory sewer reactor fed with real sewage, and the potential causes for the
      inhibitory effects observed under both high and low pH conditions. The data
      clearly showed that the sewer biofilm had the highest sulfate reduction rate at
      around neutral pH (6.5-7.5), and the activity decreased when pH was higher or
      lower. The data also suggested that the inhibiting effect at a higher pH is
      likely due to the inhibitory effects of free ammonia, while at a lower pH it is
      more likely due to the pH itself. An inhibition model formulated based on the
      above hypotheses was able to adequately describe the measured sulfide production
      rates under different pH levels and different free ammonia concentrations, as
      well as data previously reported in literature. The calibrated model was used to
      simulate sulfide production in a sewer network receiving alkali dosage. The model
      adequately predicted sulfide production in the network, which could not be
      achieved with a model not considering the pH effect. 

PMID- 24326023
TI  - Chemical and technical challenges in the analysis of central carbon metabolites
      by liquid-chromatography mass spectrometry.
AB  - This review deals with chemical and technical challenges in the analysis of small
      molecule metabolites involved in central carbon and energy metabolism via liquid
      chromatography mass-spectrometry (LC-MS). The covered analytes belong to the
      prominent pathways in biochemical carbon oxidation such as glycolysis or the
      tricarboxylic acid cycle and, for the most part, share unfavorable properties
      such as a high polarity, chemical instability or metal-affinity. The topic is
      introduced by selected examples on successful applications of metabolomics in the
      clinic. In the core part of the paper, the structural features of important
      analyte classes such as nucleotides, coenzyme A thioesters or carboxylic acids
      are linked to "problematic hotspots" along the analytical chain (sample
      preparation and-storage, separation and detection). We discuss these hotspots
      from a chemical point of view, covering issues such as analyte degradation or
      interactions with metals and other matrix components. Based on this understanding
      we propose solutions wherever available. A major notion derived from these
      considerations is that comprehensive carbon metabolomics inevitably requires
      multiple, complementary analytical approaches covering different chemical classes
      of metabolites. 

PMID- 24326024
TI  - Bartonella melophagi in Melophagus ovinus (sheep ked) collected from sheep in
      northern Oromia, Ethiopia.
AB  - Melophagus ovinus (sheep ked) is one of the most common ectoparasites that
      contributes to enormous economic losses in the productivity of sheep in many
      countries. The present study was conducted from January 2012 to July 2013 on M.
      ovinus collected from sheep at three sites in Ethiopia. Of the sheep studied,
      65.7% (88/134) were infested with M. ovinus. The prevalence of M. ovinus was 76%
      (76/100), 47% (8/17) and 23.5% (4/17) at the Kimbibit, Chacha and Shano sites,
      respectively. An overall number of 229 M. ovinus specimens (138 females, 86 males
      and five pupae) and 554 M. ovinus specimens (272 females, 282 males) were
      collected from young and adult sheep, respectively. Bartonella DNA was detected
      in 89% (694/783) of M. ovinus using a quantitative Bartonella genus-specific PCR
      assay targeting the 16S/23S rRNA intergenic spacer region. The sequencing of the
      PCR products of fragments of the gltA and rpoB genes showed 99.6-100% and 100%
      homology, respectively, with B. melophagi. Statistically significant variation
      was not noted in the overall prevalence of Bartonella DNA between female and male
      M. ovinus. All of the sheep infested with M. ovinus 100% (88/88) harbored at
      least one M. ovinus specimen that contained Bartonella DNA. This study highlights
      that B. melophagi in M. ovinus from sheep in highlands in Ethiopia possibly has
      certain zoonotic importance. 

PMID- 24326025
TI  - Protease-activated receptor-2 activates NQO-1 via Nrf2 stabilization in
      keratinocytes.
AB  - BACKGROUND: Protease-activated receptor-2 (PAR-2) mediates inflammation and
      immune responses by serine proteinases. NF-E2-related factor 2 (Nrf2) confers
      protection against tissue injury through antioxidant responses to oxidative
      stress induced by a variety of factors, including electrophilic chemicals,
      hydrogen peroxide, and ultraviolet irradiation. OBJECTIVE: In this study, we
      investigated if PAR-2 activation can stimulate Nrf2 signaling to preserve
      homeostasis in keratinocytes. METHODS: We performed western blotting, real-time
      reverse transcription polymerase chain reaction, and immunocytochemistry of
      keratinocyte cultures, as well as immunohistochemical labeling of human skin
      samples. Short interfering RNA (siRNA) was employed to confirm the effects of PAR
      2 activation. RESULTS: PAR-2 activation with a selective PAR-2 agonist peptide
      increased the nuclear level of Nrf2 protein and subsequently induced phase II
      enzyme expression. Nrf2 signaling via PAR-2 activation was confirmed with
      experiments using PAR-2-siRNA-treated keratinocytes. The activation of an Nrf2
      targeted gene by PAR-2 activation was not induced by new production of Nrf2 but
      by prolonged stabilization of Nrf2. Lesional skin samples from vitiligo patients
      showed significantly lower expression of PAR-2 and Nrf2 than control skin
      samples. CONCLUSION: Collectively, PAR-2 activation enhanced nuclear Nrf2
      translocation, and PAR-2-mediated Nrf2 activation was attributable to existing
      Nrf2 stabilization rather than de novo production. Our findings suggest that in
      addition to induction of inflammation, PAR-2 can play a chemopreventative role
      via Nrf2 stabilization in keratinocytes.

PMID- 24326026
TI  - Additional anterior plating enhances fusion in anteroposteriorly stabilized
      thoracolumbar fractures.
AB  - INTRODUCTION: To prospectively evaluate the potential radiological and clinical
      effect of the additional application of an anterior plate in anteroposteriorly
      stabilized thoracolumbar fractures. PATIENTS AND METHODS: 75 consecutive patients
      with unstable thoracolumbar fractures underwent posterior (internal fixator) and
      anterior stabilization (corpectomy cage with local autologous bone grafting). 40
      (53.3%) patients received an additional anterior plate (Group A), while 35
      (46.6%) (Group B) did not. Plain X-rays and CT-scans were obtained pre- and
      postoperatively, after 12 months and at the last follow-up (mean 32 months, range
      22-72). Loss of reduction, cage subsidence to adjacent vertebrae, fusion rates
      and clinical results were evaluated. RESULTS: 66 (87%) patients (36 Group A; 30
      Group B) were available for follow-up. Patients in both groups were comparable
      regarding age, gender, comorbidities, localization and classification of
      fracture. Average loss of reduction was 2.4 degrees  in Group A, and 3.1 degrees 
      in Group B (not significant). Cage subsidence did not differ significantly
      between both groups, too. However, after 12 months the rate of continuous osseous
      bridging between endplates was significantly higher in Group A (63% vs. 25%)
      (p<0.05). After 32 months this difference was even higher (81% vs. 33%)
      (p<0.001). The bony fusion mass was located beneath or around the anterior plate
      in 94% of patients. There was no significant difference in clinical outcome.
      CONCLUSIONS: Additional anterior plating in anteroposteriorly stabilized
      thoracolumbar fractures leads to significant faster fusion but does neither
      influence reduction loss nor cage subsidence. The anterior plate serves as a
      pathway for bone growth and increases biomechanical stability, resulting in a
      higher fusion rate.

PMID- 24326027
TI  - Locked versus standard unlocked plating of the symphysis pubis in a Type-C pelvic
      injury: a cadaver biomechanical study.
AB  - INTRODUCTION: The benefits of locked plating for pubic symphyseal disruption have
      not been established. The purpose of this biomechanical study was to determine
      whether locked plating offers any advantage over conventional unlocked plating of
      the pubic symphysis in the vertically unstable, Type-C pelvic injury. METHODS: In
      each of eight embalmed cadaver pelvis specimens, sectioning of the pubic
      symphysis in conjunction with a unilateral release of the sacroiliac,
      sacrospinous, and sacrotuberous ligaments and pelvic floor was performed to
      simulate a vertically unstable Type-C (Orthopaedic Trauma Association 61-C1.2)
      pelvic injury. The disrupted SI joint was then reduced and fixed using two 6.5mm
      cannulated screws inserted into the S1 body. Using a six-hole 3.5mm plate
      specifically designed for the symphysis pubis having both locked and unlocked
      capability, four pelvises were fixed with locked screws and four pelvises were
      fixed with standard unlocked bicortical screws. Both groups were similar based on
      a dual-emission X-ray absorptiometry evaluation (P=0.69). Each pelvis was then
      mounted on a servohydraulic materials-testing apparatus using a bilateral stance
      model to mainly stress the symphyseal fixation and was cycled up to 1 million
      cycles or failure, whichever occurred first. RESULTS: Five specimens experienced
      failure at the jig mounting/S1 vertebral body interface, occurring between
      360,000 and 715,000 cycles. Frank failure of the anterior or posterior
      instrumentation did not occur. However, end-trialing diastasis of the initial
      pubic symphysis reduction was found in all pelvises. There were no differences
      between the groups with respect to this loss of symphyseal reduction (P=0.69) or
      average cycles to failure (P=1.0). CONCLUSION: Pubic symphyseal locked plating
      does not appear to offer any advantage over standard unlocked plating for a Type
      C (OTA 61-C1.2) pelvic ring injury.

PMID- 24326028
TI  - New interlocking intramedullary radius and ulna nails for treating forearm
      diaphyseal fractures in adults: a retrospective study.
AB  - INTRODUCTION: The treatment goal for diaphyseal forearm fractures in adults is to
      restore axial and rotational stability. The treatment of these fractures with
      intrmaedullary locked nailing remains sparse. We therefore evaluated IM nails for
      treating forearm diaphyseal fractures in adults. METHODS: We retrospectively
      reviewed adult patients with isolated unilateral or bilateral fractures of the
      radius, ulna, or both, who were treated with closed or mini open reduction with a
      new IM nail between May 2008 and January 2012 and who were followed for a least 1
      year. Patients with a Galeazzi fracture, a pathological fracture or patients with
      nonunion after previous surgeries were excluded. All patients were allowed full
      range of motion without any external support. Primary outcomes were Grace and
      Eversmann rating, Disabilities of the Arm, Shoulder and Hand (DASH) scores.
      RESULTS: The 43 enrolled patients (mean age, 37 years; 32 men) had 59 forearm
      fractures: 14 isolated radius fractures, 17 isolated ulna fractures (2
      bilateral), and 28 fractures of both the radius and ulna. Mean time to fracture
      union was 13 weeks (range 10-14 weeks) for ulnar fractures and 12 weeks (range 10
      13 weeks) for radial fractures. No patient had nonunion, deep infections, or
      radioulnar synostosis. Followup ranged from 12 to 44 months. Grace and Eversmann
      ratings were excellent in 38 patients and good in 5. Mean DASH score was 6.5
      points (range 0-13.3). CONCLUSIONS: Intramedullary nailing of adult forearm
      diaphyseal fractures appears to be a good alternative to plate osteosynthesis.
      The advantages are short operative time, minimal invasive techniques, and
      sufficient stability in all planes that allows early motion without additional
      fracture support.

PMID- 24326029
TI  - Does normalized signal intensity of cervical discs on T2 weighted MRI images
      change in whiplash patients?
AB  - PURPOSE: We tested the hypothesis that whiplash trauma leads to changes of the
      signal intensity of cervical discs in T2-weighted images. METHODS AND MATERIALS:
      50 whiplash patients (18-65 years) were examined within 48h after motor vehicle
      accident, and again after 3 and 6 months and compared to 50 age- and sex-matched
      controls. Signal intensity in ROI's of the discs at the levels C2/3 to C7/T1 and
      the adjacent vertebral bodies were measured on sagittal T2 weighted MR images and
      normalized using the average of ROI's in fat tissue. The contrast between discs
      and both adjacent vertebrae was calculated and disc degeneration was graded by
      the Pfirrmann-grading system. RESULTS: Whiplash trauma did not have a significant
      effect on the normalized signals from discs and vertebrae, on the contrast
      between discs and adjacent vertebrae, or on the Pfirrmann grading. However, the
      contrast between discs and adjacent vertebrae and the Pfirrmann grading showed a
      strong correlation. In healthy volunteers, the contrast between discs and
      adjacent vertebrae and Pfirrmann grading increased with age and was dependent on
      the disc level. CONCLUSION: We could not find any trauma related changes of
      cervical disc signal intensities. Normalized signals of discs and Pfirrmann
      grading changed with age and varied between disc levels with the used MR
      sequence.

PMID- 24326030
TI  - Larval nutrition differentially affects adult fitness and Plasmodium development
      in the malaria vectors Anopheles gambiae and Anopheles stephensi.
AB  - BACKGROUND: Mosquito fitness is determined largely by body size and nutritional
      reserves. Plasmodium infections in the mosquito and resultant transmission of
      malaria parasites might be compromised by the vector's nutritional status. We
      studied the effects of nutritional stress and malaria parasite infections on
      transmission fitness of Anopheles mosquitoes. METHODS: Larvae of Anopheles
      gambiae sensu stricto and An. stephensi were reared at constant density but with
      nutritionally low and high diets. Fitness of adult mosquitoes resulting from each
      dietary class was assessed by measuring body size and lipid, protein and glycogen
      content. The size of the first blood meal was estimated by protein analysis.
      Mosquitoes of each dietary class were fed upon a Plasmodium yoelii nigeriensis
      infected mouse, and parasite infections were determined 5 d after the infectious
      blood meal by dissection of the midguts and by counting oocysts. The impact of
      Plasmodium infections on gonotrophic development was established by dissection.
      RESULTS: Mosquitoes raised under low and high diets emerged as adults of
      different size classes comparable between An. gambiae and An. stephensi. In both
      species low-diet females contained less protein, lipid and glycogen upon
      emergence than high-diet mosquitoes. The quantity of larval diet impacted
      strongly upon adult blood feeding and reproductive success. The prevalence and
      intensity of P. yoelii nigeriensis infections were reduced in low-diet mosquitoes
      of both species, but P. yoelii nigeriensis impacted negatively only on low-diet,
      small-sized An. gambiae considering survival and egg maturation. There was no
      measurable fitness effect of P. yoelii nigeriensis on An. stephensi. CONCLUSIONS:
      Under the experimental conditions, small-sized An. gambiae expressed high
      mortality, possibly caused by Plasmodium infections, the species showing distinct
      physiological concessions when nutrionally challenged in contrast to well-fed,
      larger siblings. Conversely, An. stephensi was a robust, successful vector
      regardless of its nutrional status upon emergence. The data suggest that small
      sized An. gambiae, therefore, would contribute little to malaria transmission,
      whereas this size effect would not affect An. stephensi.

PMID- 24326031
TI  - Restrictive cardiomyopathy mutations demonstrate functions of the C-terminal end
      segment of troponin I.
AB  - The C-terminal end-segment of Troponin I (TnI) corresponding to the last 27-33
      amino acids is the most conserved structure of TnI and interacts with tropomyosin
      in a Ca(2+)-regulated manner, suggesting a role in muscle relaxation. Mutations
      in the C-terminal end-segment of cardiac TnI cause restrictive cardiomyopathy.
      Here we demonstrate that mouse cardiac TnI containing R193H or R205H mutation
      have significantly conformational changes in the region interfacing with troponin
      T (TnT) and increased binding affinity for TnT. These restrictive cardiomyopathy
      mutations also exhibit increased binding affinity for troponin C at pCa 4. The
      effects of R193H mutation were more profound than that of R205H. Tertiary
      troponin complex was reconstituted using the TnI mutants and a mini TnT lacking
      tropomyosin-binding sites to examine the interaction between the C-terminal end
      segment of TnI and tropomyosin. The results showed that, R193H, but not R205H,
      caused a moderate but statistically significant increase in the binding affinity
      for tropomyosin at pCa 9. Similar trend was observed at pCa 5.5 but not pCa 4.
      These results provide novel evidence for the function of the C-terminal end
      segment of TnI, where mutations with conformational effects alter TnI's
      interaction with other troponin subunits and tropomyosin to cause diastolic
      dysfunction. 

PMID- 24326032
TI  - Vasculitis associated with large granular lymphocyte (LGL) leukemia: presentation
      and treatment outcomes of 11 cases.
AB  - OBJECTIVE: The association between vasculitis and large granular lymphocyte (LGL)
      leukemia has rarely been reported or investigated. Thus, we assessed the clinical
      and biological phenotypes of LGL leukemia associated with vasculitis. RESULTS: We
      studied a series of 11 patients displaying LGL leukemia associated with
      vasculitis (LAV). The mean age at diagnosis of LGL leukemia was 60.3 years; there
      were nine women and two men. The mean follow-up period was 45 months. The main
      LGL lineage was T-LGL (10 patients), and only one NK-LGL was identified. Clinical
      and biological features of T-LGL leukemia were compared with those from the 2009
      French T-LGL registry. We did not find any relevant differences except that
      patients with LAV were predominantly female (p < 0.05). The most frequently
      observed vasculitis was cryoglobulinemia (n = 5). Three patients presented with
      cutaneous leukocytoclastic angiitis, two patients had ANCA-negative microscopic
      polyangiitis, and one patient had giant cell arteritis. The main clinical
      features involved the skin, e.g., purpura (91%), arthralgia (37%), peripheral
      neuritis (27%), and renal glomerulonephritis (18%). The most frequent histologic
      finding was leucocytoclastic vasculitis (54%). The rate of complete remission was
      high; i.e., 80%. A minority of patients had a vasculitis relapse (27%). Three
      patients (27%) died; one death was related to LGL leukemia (acute infection) and
      the two other deaths were related to vasculitis (both with heart failure).
      CONCLUSION: We conclude that vasculitis is overrepresented in the population of
      LGL patients, LAV predominantly affects women, vasculitis preferentially affects
      the small vessels, and LAV has high rate of complete response.

PMID- 24326033
TI  - A systematic review and meta-analysis on the safety and efficacy of febuxostat
      versus allopurinol in chronic gout.
AB  - OBJECTIVE: To evaluate the safety and efficacy of febuxostat compared to
      allopurinol for the treatment of chronic gout. METHODS: We did a systematic
      review and meta-analysis of randomized and non-randomized controlled trials that
      compared oral febuxostat to oral allopurinol for treatment of chronic gout. Two
      reviewers independently selected studies, assessed study quality, and extracted
      data. Risk ratios (RR) were calculated with random effects and were reported with
      corresponding 95% confidence intervals (CI). RESULTS: From 1076 potentially
      relevant citations, 7 studies and 25 associated publications met inclusion
      criteria; 5 studies were ultimately included in the analysis. Febuxostat did not
      reduce the risk of gout flares compared with allopurinol (RR = 1.16, 95% CI =
      1.03-1.30, I(2) = 44%). Overall, the risk of any adverse event was lower in
      febuxostat recipients compared to allopurinol (RR = 0.94, 95% CI = 0.90-0.99,
      I(2) = 13%). Patients receiving febuxostat were more likely to achieve a serum
      uric acid of <6 mg/dl than allopurinol recipients (RR = 1.56, 95% CI = 1.22-2.00,
      I(2) = 92%). Subgroup analysis did not indicate any significant difference
      between high- and low-dose febuxostat on the risk of gout flares. CONCLUSION:
      Although febuxostat was associated with higher likelihood of achieving a target
      serum uric acid level of <6 mg/dl, there was significant heterogeneity in the
      pooled results. There was no evidence that febuxostat is superior to allopurinol
      for clinically relevant outcomes. Given its higher cost, febuxostat should not be
      routinely used for chronic gout.

PMID- 24326034
TI  - The Crafoord Prize in Polyarthritis 2013: significant discoveries and remaining
      challenges.

PMID- 24326035
TI  - Proceedings of the 5th annual perspectives in rheumatic diseases.
AB  - OBJECTIVES: Update on rheumatic diseases and their intersection with dermatology.
      RESULTS: This continuing medical education conference included more than 25
      presentations and interactive sessions from leading experts in managing rheumatic
      diseases, comorbid conditions and related dermatologic diseases. Multiple areas
      were discussed, including: treating newly diagnosed rheumatoid arthritis;
      comparing Biologics in rheumatoid arthritis; examining changed approaches to
      treating SLE, psoriasis, psoriatic arthritis, ankylosing spondylitis, gout and
      vasculitis. Also visited were new understandings regarding chronic pain and
      osteoporosis. CONCLUSIONS: Multiple presentations and interactive sessions from
      leading experts in the management of rheumatic diseases emphasized the
      interconnection between rheumatology and dermatology. Practical management
      approaches to both specialties and their sequelae were discussed. Additional
      content from the conference is available at www.globalacademycme.com and through
      Rheumatology News at www.rheumatologynews.com.

PMID- 24326036
TI  - Removal of dorzolamide from biomedical wastewaters with adsorption onto graphite
      oxide/poly(acrylic acid) grafted chitosan nanocomposite.
AB  - A novel graphite oxide/poly(acrylic acid) grafted chitosan nanocomposite (GO/CSA)
      was prepared and used as biosorbent for the removal of pharmaceutical compound
      (dorzolamide) from biomedical synthetic wastewaters. The performance was
      evaluated taking into account pH, kinetics and thermodynamics of adsorption.
      GO/CSA presented higher adsorption capacity in comparison with the parent
      materials (graphite oxide and poly(acrylic acid) grafted chitosan). All
      adsorbents prepared were characterized using X-ray diffraction (XRD), scanning
      electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and
      potentiometric titration. The surface features were also evaluated after the
      dorzolamide adsorption in order to derive the adsorption mechanism. It was
      suggested that the reactive groups of GO and CSA can interact with the amino
      groups of dorzolamide and mainly the abundance of carboxyl groups of GO/CSA
      composite was the main reason for its enhanced adsorption capacity. 

PMID- 24326037
TI  - The purification of crude glycerol derived from biodiesel manufacture and its use
      as a substrate by Rhodopseudomonas palustris to produce hydrogen.
AB  - Crude glycerol (CG) from biodiesel production is often contaminated with several
      compounds, including saponified fatty acids (SFAs). Photofermentative growth of
      Rhodopseudomonas palustris on glycerol leads to hydrogen production; however, R.
      palustris is inhibited by SFAs. This study examines inhibition of R. palustris by
      SFAs, finding that, with increasing concentration of SFA, growth rate falls,
      reaching zero at an SFA concentration of 0.2 mM. Methods for purifying CG were
      examined, namely (i) treatment with ethanol and activated carbon, (ii) pH
      adjustment, (iii) solvent extraction, and (iv) precipitation of the fatty acids
      with calcium. The rates of growth and production of hydrogen were investigated
      using CG treated by these methods. It was found that treatment with activated
      carbon, pH reduction, and calcium precipitation reduced inhibition, while solvent
      extraction was effective only when used in conjunction with pH adjustment. These
      treatments allow crude glycerol to be used for hydrogen production by R.
      palustris.

PMID- 24326038
TI  - Immune profiles of CD4+ lymphocyte subsets in breast cancer tumor draining lymph
      nodes.
AB  - Tumor draining lymph nodes form the first line of defense against tumor
      dissemination. Lymphocyte subpopulations activated during anti-tumor response
      determine the outcome of host-tumor interaction. In the present study we explored
      the percentages of different subtypes of CD4+ lymphocytes, including regulatory
      cells (TFR, CD25-, and CD25+ Treg cells), helper subsets (Th1, Th2, Th17, and Tfh
      cells), and the expression level of their cognate cytokines (IFNgamma, IL4, and
      IL17) in tumor draining lymph nodes of patients with breast cancer, and compared
      the results between node negative (LN-) and node positive (LN+) patients. Forty
      seven sentinel and non-sentinel auxiliary lymph nodes with or without tumor
      involvement were collected from untreated breast cancer patients undergoing
      surgical resection. Mononuclear cells obtained from fresh homogenized lymph nodes
      were subjected to surface and intracellular staining by flow cytometry. The
      results revealed the presence of a newly identified subtype of regulatory T
      cells, TFR, as well as CD25- Treg cells in TDLNs of the breast cancer patients.
      In addition, evaluation of different helper and regulatory subgroups of CD4+ T
      lymphocytes showed that upon metastasis of tumor cells to lymph nodes together
      with the progression of the disease stage, the immune responses changed from an
      inflammatory to an inhibitory state, as evidenced by a reduction in pro
      inflammatory and anti-tumor cytokines, IL17 and IFNgamma, as well as an increase
      in pro-tumorigenic phenotypes, Th2 and Treg cells. This situation may provide a
      favorable condition for tumor growth and spread. 

PMID- 24326039
TI  - The correlation between the number of eligible patients in routine clinical
      practice and the low recruitment level in clinical trials: a retrospective study
      using electronic medical records.
AB  - BACKGROUND: A number of clinical trials have encountered difficulties enrolling a
      sufficient number of patients upon initiating the trial. Recently, many screening
      systems that search clinical data warehouses for patients who are eligible for
      clinical trials have been developed. We aimed to estimate the number of eligible
      patients using routine electronic medical records (EMRs) and to predict the
      difficulty of enrolling sufficient patients prior to beginning a trial. METHODS:
      Investigator-initiated clinical trials that were conducted at Kyoto University
      Hospital between July 2004 and January 2011 were included in this study. We
      searched the EMRs for eligible patients and calculated the eligible EMR patient
      index by dividing the number of eligible patients in the EMRs by the target
      sample size. Additionally, we divided the trial eligibility criteria into
      corresponding data elements in the EMRs to evaluate the completeness of mapping
      clinical manifestation in trial eligibility criteria into structured data
      elements in the EMRs. We evaluated the correlation between the index and the
      accrual achievement with Spearman's rank correlation coefficient. RESULTS:
      Thirteen of 19 trials did not achieve their original target sample size. Overall,
      55% of the trial eligibility criteria were mapped into data elements in EMRs. The
      accrual achievement demonstrated a significant positive correlation with the
      eligible EMR patient index (r = 0.67, 95% confidence interval (CI), 0.42 to
      0.92). The receiver operating characteristic analysis revealed an eligible EMR
      patient index cut-off value of 1.7, with a sensitivity of 69.2% and a specificity
      of 100.0%. CONCLUSIONS: Our study suggests that the eligible EMR patient index
      remains exploratory but could be a useful component of the feasibility study when
      planning a clinical trial. Establishing a step to check whether there are likely
      to be a sufficient number of eligible patients enables sponsors and investigators
      to concentrate their resources and efforts on more achievable trials.

PMID- 24326040
TI  - Acceleration of tooth movement during orthodontic treatment--a frontier in
      orthodontics.
AB  - Nowadays, there is an increased tendency for researches to focus on accelerating
      methods for tooth movement due to the huge demand for adults for a shorter
      orthodontic treatment time. Unfortunately, long orthodontic treatment time poses
      several disadvantages like higher predisposition to caries, gingival recession,
      and root resorption. This increases the demand to find the best method to
      increase tooth movement with the least possible disadvantages. The purpose of
      this study is to view the successful approaches in tooth movement and to
      highlight the newest technique in tooth movement. A total of 74 articles were
      reviewed in tooth movement and related discipline from 1959 to 2013. There is a
      high amount of researches done on the biological method for tooth movement;
      unfortunately, the majority of them were done on animals. Cytokine, PTH, vitamin
      D, and RANKL/RANK/OPG show promising results; on the other hand, relaxin does not
      accelerate tooth movement, but increases the tooth mobility. Low-level laser
      therapy has shown positive outcome, but further investigation should be done for
      the best energy and duration to achieve the highest success rate. Surgical
      approach has the most predictable outcomes but with limited application due to
      its aggressiveness. Piezocision technique is considered one of the best surgical
      approaches because it poses good periodontal tissue response and excellent
      aesthetic outcome. Due to the advantages and disadvantages of each approach,
      further investigations should be done to determine the best method to accelerate
      tooth movement. 

PMID- 24326041
TI  - Evaluation of ultra-deep targeted sequencing for personalized breast cancer care.
AB  - INTRODUCTION: The increasing number of targeted therapies, together with a deeper
      understanding of cancer genetics and drug response, have prompted major
      healthcare centers to implement personalized treatment approaches relying on high
      throughput tumor DNA sequencing. However, the optimal way to implement this
      transformative methodology is not yet clear. Current assays may miss important
      clinical information such as the mutation allelic fraction, the presence of sub
      clones or chromosomal rearrangements, or the distinction between inherited
      variants and somatic mutations. Here, we present the evaluation of ultra-deep
      targeted sequencing (UDT-Seq) to generate and interpret the molecular profile of
      38 breast cancer patients from two academic medical centers. METHODS: We
      sequenced 47 genes in matched germline and tumor DNA samples from 38 breast
      cancer patients. The selected genes, or the pathways they belong to, can be
      targeted by drugs or are important in familial cancer risk or drug metabolism.
      RESULTS: Relying on the added value of sequencing matched tumor and germline DNA
      and using a dedicated analysis, UDT-Seq has a high sensitivity to identify
      mutations in tumors with low malignant cell content. Applying UDT-Seq to matched
      tumor and germline specimens from the 38 patients resulted in a proposal for at
      least one targeted therapy for 22 patients, the identification of tumor sub
      clones in 3 patients, the suggestion of potential adverse drug effects in 3
      patients and a recommendation for genetic counseling for 2 patients. CONCLUSION:
      Overall our study highlights the additional benefits of a sequencing strategy,
      which includes germline DNA and is optimized for heterogeneous tumor tissues.

PMID- 24326042
TI  - Association of cardiovascular risk factors and troponin elevation after
      generalized tonic-clonic seizures.
AB  - PURPOSE: Troponins are very sensitive biomarkers of myocardial injury.
      Conflicting data regarding elevation of troponin levels following a generalized
      tonic-clonic (GTC) seizure have been reported. In this study we hypothesized that
      troponin elevation after a GTC seizure occurs more frequently in patients with
      cardiovascular risk factors. METHODS: Patients who presented to the ER after a
      single GTC seizure with troponin levels assessed by cardiac troponin T (cTnT) and
      drawn within 12h of the GTC seizure were included. Patients with cardiac
      symptoms, elevated CPK levels or renal insufficiency were excluded. The frequency
      and risk factors for elevated cTnT levels were analyzed. RESULTS: Fourteen
      patients with a mean age of 54 years (range: 19-87 years) were included. Four
      patients (28.6%) had elevated cTnT levels (mean=0.06MUg/L; range: 0.035
      0.076MUg/L). Patients with elevated cTnT levels were significantly older than
      those with normal levels (77.5 years vs. 45.5 years; P=0.03). Of the eight
      patients 60 years of age and older, four (50%) had elevated cTnT levels. The
      coronary heart disease (CHD) score was significantly higher in patients with
      elevated cTnT levels compared to those with normal levels (13.5 vs. 9.75,
      P=0.012). CONCLUSIONS: Elevated troponin levels can occur after a GTC seizure.
      Patients at risk are the elderly and those with cardiovascular risk factors. Our
      results suggest that elevation of troponin levels after a GTC seizure reflects a
      minor ischemic cardiac injury related to the demand ischemia during the
      sympathetic overactivity that accompanies a GTC seizure.

PMID- 24326043
TI  - No association between polymorphisms in the calcium homeostasis modulator 1 gene
      and mesial temporal lobe epilepsy risk in a Chinese population.
AB  - PURPOSE: Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of
      epilepsies in adults. The calcium homeostasis modulator 1 gene (CALHM1) has been
      considered one of the candidate genes that play a role in epileptogenesis due to
      its function in calcium homeostasis and amyloid beta (Abeta) regulation.
      Recently, the association of a single nucleotide polymorphism (rs11191692) of
      CALHM1 has been reported to be associated with MTLE in Han Chinese, but
      independent replication is needed. In the present study, rs11191692 and rs2986017
      of CALHM1 were determined in 512 MTLE patients and 412 control subjects to
      investigate the possible involvement of CALHM1 in the etiology of MTLE. METHOD:
      Genotyping was determined by polymerase chain reaction-restriction fragment
      length polymorphism method. Major statistical analyses were performed by SAS.
      RESULTS: No significant differences in the genotypic or allelic frequencies of
      both single-nucleotide polymorphisms were revealed between subjects with and
      without MTLE (rs11191692: P=0.890 and 0.230; rs2986017: P=0.581 and 0.072).
      Further stratification analysis by gender and age, and analysis of clinical
      features in relation to MTLE also yielded negative results. CONCLUSION:
      rs11191692 and rs2986017 of CALHM1 do not contribute substantially to MTLE in Han
      Chinese.

PMID- 24326044
TI  - [Truthfully - would you have known?].

PMID- 24326045
TI  - [Poisoning with Amanita mushrooms].

PMID- 24326047
TI  - [Imaging of Lemierre in children and young adults].
AB  - PURPOSE: The aim of this study is to describe the role of imaging in the medical
      care of Lemierre Syndrome and to describe its US, CT and MRI features. PATIENTS
      AND METHODS: Files of patients diagnosed with Lemierre Syndrome between 2005 and
      2011 at CHUV hospital have been analysed retrospectively to define its imaging
      semiology. RESULTS: IJV thrombosis was demonstrated by US, CT and MRI. Septic
      pulmonary emboli were detected by CT. Complications of the Lemierre Syndrome were
      depicted by MR and CT. CONCLUSION: US, CT or MR evidence of IJV thrombosis and
      chest CT suggestive of septic emboli, should lead the physician to diagnose
      Lemierre Syndrome, which in case of insufficient therapy can lead to death.

PMID- 24326048
TI  - [The treatment of Parkinson's disease].
AB  - Parkinson's disease belongs to the most prevalent neurodegenerative disorders and
      manifests both with motor and non-motor symptoms. Symptomatic treatment of this
      disorder became more multifaceted over the past years: besides classical
      dopaminergic drugs and physiotherapy, novel invasive escalation treatment
      strategies became gold standard in many countries. On the other hand, non-motor
      symptoms significantly impacts quality of life in many patients which
      necessitates initiation of adequate therapy.

PMID- 24326049
TI  - [Positional plagiocephaly in infancy: diagnosis and management].
AB  - Positional plagiocephaly in the newborn corresponds to a posterior flattening and
      asymetry of the head. Its incidence has significantly increased since the "back
      to sleep" campain in the nineteen nineties to prevent sudden infant death
      syndrome. The posterior deformation usually worsens during the first six months
      of life when the skull is susceptible to posterior constant pressure which
      induces the deformation. Spontaneous outcome can be favorable. Treatment is
      always conservative and consists in positionnal exercise, physiotherapy and
      osteopathy. In some cases treatment with a helmet is recommended for a period of
      three months usually. Posterior positionnal plagiocephaly has no consequences on
      the brain's developement an is considered as an esthetic issue. In most cases
      good results are obtained after management with a custom fitted helmet when
      needed. 

PMID- 24326052
TI  - [Ginseng in cancer-induced fatigue - more than a placebo].

PMID- 24326050
TI  - ["Is there a doctor on board?" - legal aspects of medical care in emergency
      situations during spare time].
AB  - Medical emergencies on international flights are not uncommon. In these
      situations the question often arises whether physicians are obliged to render
      first aid and whether omission leads to legal consequences. The general
      obligation to aid those in need applies to everyone, not only to physicians.
      Evading this duty makes liable to prosecution for omittance of defence of a third
      person in line with Art. 128 of the Swiss Penal Code, punishable by custodial
      sentence up to three years or an equivalent punitive fine. Vocational and
      professional law extend the duty to aid for physicians to urgent cases. Although
      resulting from the performance of a legal obligation, malpractice occurred in the
      course of first aid can lead to claims for compensation - even from foreign
      patients, and that according to their own domestic law. 

PMID- 24326053
TI  - [Blind administration of statins could harm the eyes].

PMID- 24326056
TI  - [CME ultrasound diagnosis 55. Pseudoaneurysm of the gastroduodenal artery].

PMID- 24326059
TI  - Endovascular SilverHawk directional atherectomy for thromboangiitis obliterans
      with occlusion of the popliteal artery.
AB  - Thromboangiitis obliterans (TAO), also known as Buerger disease, is a
      nonatherosclerotic segmental inflammatory disease of small and medium-sized
      arteries of the distal extremities occurring predominantly in young men who are
      long-term tobacco smokers. We treated 2 patients who presented with TAO involving
      popliteal and tibial arteries. Directional atherectomy with a SilverHawk device
      was used to recanalize the arteries without major complications. During follow-up
      conducted using computed tomography or sonography, we observed that the treated
      vessels remained patent. These cases report illustrate the feasibility and
      immediate effectiveness of endovascular SilverHawk directional atherectomy in TAO
      patients with occlusion of the popliteal arteries. 

PMID- 24326060
TI  - Peroneal nerve palsy caused by popliteal pseudoaneurysm in a child with
      hereditary multiple exostosis.
AB  - A 12-year-old boy with a family history of hereditary multiple exostosis
      presented with a 3-week history of progressive knee swelling. The clinical
      examination revealed drop foot and a loss of extension in his right knee.
      Evaluation with color duplex ultrasonography, computed tomography angiography,
      and magnetic resonance imaging revealed a popliteal artery pseudoaneurysm
      associated with exostosis from the distal femur. This patient was diagnosed as
      having peroneal neuropathy caused by popliteal artery pseudoaneurysm compressing
      the nerve in the right popliteal fossa. The pseudoaneurysm was repaired
      primarily, and the exostosis was excised during the operation. Pain and knee
      contracture resolved after surgery. The patient was then referred to physical
      therapy for the management of drop foot. 

PMID- 24326061
TI  - Effects of crown-root angle on stress distribution in the maxillary central
      incisors' PDL during application of intrusive and retraction forces: a three
      dimensional finite element analysis.
AB  - BACKGROUND: Different crown-root angulations of maxillary central incisors can be
      assumed as a potential reason for many underscored outcomes of orthodontic
      treatments. The aim of this study was to determine the effects of the different
      crown-root angles on stress distributions in the maxillary central incisor's
      periodontal ligament (PDL) during application of intrusive and retraction forces
      using a 3D finite element method. METHODS: Two models of a maxillary central
      incisor were constructed using ANSYS software: the first one with an angle of
      166.7 degrees  (as a sample of the maxillary central incisor in a class II,
      division 2 patient) and the other one with an angle of 173.4 degrees  (normal
      angulation). Each of the samples was loaded twice by an intrusive force (0.25 N)
      and a retraction force (0.5 N) through the ideal position of brackets. RESULTS:
      FEM results showed little difference between stress distributions in the two
      models during intrusion (ten thousandth) compared to retraction (thousandth). In
      the application of retraction force, the stress concentration on the curved tooth
      was less than the other. CONCLUSION: To produce similar patterns of stress in the
      PDL, orthodontists can apply 1.18 times heavier retraction forces on the
      maxillary central incisors in class II, division 2 patients compared to class I
      patients.

PMID- 24326062
TI  - Diagnostic performance of combined canine and second molar maturity for
      identification of growth phase.
AB  - BACKGROUND: The objective of this research is to analyze the diagnostic
      performance of the circumpubertal dental maturation stages of the mandibular
      canine and second molar, as individual teeth and in combination, for the
      identification of growth phase. METHODS: A total of 300 healthy subjects, 192
      females and 108 males, were enrolled in the study (mean age, 11.4+/-2.4 years;
      range, 6.8 to 17.1 years). Dental maturity was assessed through the calcification
      stages from panoramic radiographs of the mandibular canine and second molar.
      Determination of growth phase (as pre-pubertal, pubertal, and post-pubertal) was
      carried out according to the cervical vertebral maturation method. The diagnostic
      performances of the dental maturation stages, as both individual teeth and in
      combination, for the identification of the growth phase were evaluated using
      positive likelihood ratios (LHRs), with a threshold of >=10 for satisfactory
      performance. RESULTS: For the individual dental maturation stages, most of these
      positive LHRs were <=1.6, with values>=10 seen only for the identification of the
      pre-pubertal growth phase for canine stage F and second molar stages D and E, and
      for the post-pubertal growth phase for second molar stage H. All of the combined
      dental maturation stages yielded positive LHRs up to 2.6. CONCLUSIONS: Dental
      maturation of either individual or combined teeth has little role in the
      identification of the pubertal growth spurt and should not be used to assess
      timing for treatments that are required to be performed at this growth phase.

PMID- 24326063
TI  - Self-expandable metal stents for malignant colonic obstruction: data from a
      retrospective regional SIED-AIGO study.
AB  - BACKGROUND: Self-expandable metal stents are a non-surgical option for the
      treatment of symptomatic malignant colorectal obstruction as palliative treatment
      or as a bridge to surgery. AIMS: To report data from a regional study on self
      expandable metal stent (SEMS) placement for malignant colorectal obstruction.
      METHODS: Two hundred and four patients (male 54.9%, mean age of 69.5 +/- 14.2)
      were retrospectively evaluated and data on technical and clinical success, and
      complications, were analyzed. RESULTS: Technical and clinical success rates were
      99% and 94.6% respectively, with 36.7% treated on an emergency basis and 63.3%
      electively. Palliative treatment was administered to 70.1%, and as a bridge to
      surgery for 29.9%. Complications were 17 neoplastic ingrowths, 10 stent
      migrations, and 4 perforations. Palliative treatment was associated with a higher
      risk of stent ingrowth (p=0.003), and chemotherapy with a lower risk of stent
      ingrowth (p=0.009). CONCLUSION: This regional study, although it has certain
      limitations, confirms the positive role of self-expandable metal stents in the
      treatment of symptomatic malignant colorectal obstruction, and that chemotherapy
      decreases the risk of ingrowth.

PMID- 24326064
TI  - Sorption of selected veterinary antibiotics onto dairy farming soils of
      contrasting nature.
AB  - The sorption potential for three sulfonamides (SAs), sulfamethoxazole (SMO),
      sulfachloropyridazine (SCP) and sulfamethazine (SM) and a macrolide, tylosin
      tartrate (TT) was assessed on six New Zealand dairy farming soils of contrasting
      physico-chemical properties. Kinetics studies showed that the sorption was rapid
      in the first few hours of the contact time (0-2h for SA and 0-4h for TT) and
      thereafter apparent equilibrium was achieved. Batch sorption isotherm data
      revealed that the degree of isotherm linearity (N) for SCP and SM varied between
      0.50 and 1.08 in the six soils. Isotherms of both TT and SMO were mostly non
      linear with the degree of non-linearity for TT (N=0.38-0.71) being greater than
      for SMO (0.42-0.75) in all soils except Manawatu (TT) and Te Kowhai (SMO) where a
      linear pattern was observed. Concentration-dependent effective distribution
      coefficient (Kd(eff)) values for the SMO, SCP and SM antibiotics in the soils
      ranged from 0.85 to 16.35 L kg(-1), while that for TT was 1.6 to 1,042 L kg(-1).
      The sorption affinity for all soils followed an order: TT>SCP>SM>SMO. Remarkable
      high sorption for tylosin in Matawhero soil as compared to other soils was
      attributed to the presence of oxygen containing acidic polar functional groups as
      evident in the FT-IR spectra of the soil. Furthermore, it was hypothesised that
      sorption of TT onto soils was mostly driven by metal oxide-surface mediated
      transformations whereas for sulfonamides it was primarily due to hydrophobic
      interactions.

PMID- 24326065
TI  - Development and initial evaluation of an Internet-based support system for face
      to-face cognitive behavior therapy: a proof of concept study.
AB  - BACKGROUND: Evidence-based psychological treatments, such as cognitive behavior
      therapy (CBT), have been found to be effective in treating several anxiety and
      mood disorders. Nevertheless, issues regarding adherence are common, such as poor
      patient compliance on homework assignments and therapists' drifting from strictly
      evidence-based CBT. The development of Internet-delivered CBT (ICBT) has been
      intensive in the past decade and results show that guided ICBT can be as
      effective as face-to-face CBT but also indicate a need to integrate the two forms
      of CBT delivery. OBJECTIVE: In this study, we developed and tested a new
      treatment format in which ICBT and face-to-face therapy were blended. We designed
      a support system accessible via the Internet (using a computer or an Apple iPad)
      for patients and therapists delivering CBT face-to-face. The support system
      included basic CBT components and a library of interventions gathered from
      existing ICBT manuals. METHODS: The study involved 15 patients with mild to
      moderate anxiety or depression (or both). Eight therapists conducted the
      treatments. All participants were interviewed after the nine-week intervention.
      Further, patients provided self-reports on clinical measures pre- and post-trial,
      as well as at a 12-month follow-up. RESULTS: A reduction was found in symptom
      scores across all measures. The reliable change index ranged from 60% to 87% for
      depression and anxiety. Large effect sizes (Cohen's d) ranging from 1.62 (CI 95%
      0.59-2.66) to 2.43 (CI 95% 1.12-3.74) were found. There were no missing data and
      no treatment dropouts. In addition, the results had been maintained at the 12
      month follow-up. Qualitative interviews revealed that the users perceived the
      support system as beneficial. CONCLUSIONS: The results suggest that modern
      information technology can effectively blend with face-to-face treatments and be
      used to facilitate communication and structure in therapy, thus reducing
      therapist drift.

PMID- 24326066
TI  - Endothelial dysfunction after pregnancy-induced hypertension.
AB  - OBJECTIVE: To carry out long-term analysis of the presence of endothelial
      dysfunction after the development of pregnancy-induced hypertension (PIH).
      METHODS: In a retrospective cohort study, data were analyzed from 60 women who
      delivered at a tertiary maternity hospital in Fortaleza, Ceara, Brazil, between
      1992 and 2002. Thirty women had a history of PIH and 30 had no history of
      complications. Anthropometric and laboratory data were collected, and endothelial
      function was evaluated by flow-mediated dilatation of the brachial artery.
      Continuous variables were analyzed via Student t test, and Mann-Whitney test was
      used to compare means. Clinical and metabolic measures were categorized according
      to cardiovascular risk by cutoff points determined by national consensus; chi2
      and Fisher exact tests were used to compare the groups. Relative risk was
      calculated for variables that were statistically significant (P<0.05). RESULTS:
      Women with a history of PIH had higher body mass index (P=0.03), systolic blood
      pressure (P=0.03), low-density lipoprotein cholesterol (P=0.02), and fasting
      glucose (P=0.02) compared with women with no pregnancy complications. The
      frequency of endothelial dysfunction was 60% among all women, with a significant
      difference between the 2 groups (P=0.01). CONCLUSION: Women with a history of PIH
      were found to have a higher frequency of long-term endothelial dysfunction.

PMID- 24326067
TI  - BSA-boronic acid conjugate as lectin mimetics.
AB  - We report bovine serum albumin (BSA)-boronic acid (BA) conjugates as lectin
      mimetics and their glyco-capturing capacity. The BSA-BA conjugates were
      synthesized by amidation of carboxylic acid groups in BSA with aminophenyl
      boronic acid in the presence of EDC, and were characterized by Alizarin Red S
      (ARS) assay and SDS-PAGE gel. The BSA-BA conjugates were immobilized onto
      maleimide-functionalized silica beads and their sugar capturing capacity and
      specificity were confirmed by ARS displacement assay. Further, surface plasmon
      resonance (SPR) analysis of the glyco-capturing activity of the BSA-BA conjugates
      was conducted by immobilizing BSA-BA onto SPR gold chip. Overall, we demonstrated
      a BSA-BA-based lectin mimetics for glyco-capturing applications. These lectin
      mimetics are expected to provide an important tool for glycomics and biosensor
      research and applications. 

PMID- 24326068
TI  - Characterization of NAADP-mediated calcium signaling in human spermatozoa.
AB  - Ca(2+) signaling in spermatozoa plays a crucial role during processes such as
      capacitation and release of the acrosome, but the underlying molecular mechanisms
      still remain unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a
      potent Ca(2+)-releasing second messenger in a variety of cellular processes. The
      presence of a NAADP synthesizing enzyme in sea urchin sperm has been previously
      reported, suggesting a possible role of NAADP in sperm Ca(2+) signaling. In this
      work we used in vitro enzyme assays to show the presence of a novel NAADP
      synthesizing enzyme in human sperm, and to characterize its sensitivity to Ca(2+)
      and pH. Ca(2+) fluorescence imaging studies demonstrated that the permeable form
      of NAADP (NAADP-AM) induces intracellular [Ca(2+)] increases in human sperm even
      in the absence of extracellular Ca(2+). Using LysoTracker, a fluorescent probe
      that selectively accumulates in acidic compartments, we identified two such
      stores in human sperm cells. Their acidic nature was further confirmed by the
      reduction in staining intensity observed upon inhibition of the endo-lysosomal
      proton pump with Bafilomycin, or after lysosomal bursting with glycyl-l
      phenylalanine-2-naphthylamide. The selective fluorescent NAADP analog, Ned-19,
      stained the same subcellular regions as LysoTracker, suggesting that these stores
      are the targets of NAADP action.

PMID- 24326069
TI  - V-ATPase-dependent luminal acidification is required for endocytic recycling of a
      yeast cell wall stress sensor, Wsc1p.
AB  - Wsc1p is a major cell wall sensor protein localized at the polarized cell
      surface. The localization of Wsc1p is maintained by endocytosis and recycling
      from endosomes back to the cell surface, but changes to the vacuole when cells
      are subjected to heat stress. Exploiting this unique property of Wsc1p, we
      screened for yeast single-gene deletion mutants exhibiting defects in Wsc1p
      trafficking. By expressing 3GFP-tagged Wsc1p in mutants with deleted genes whose
      function is related to intracellular trafficking, we identified 5 gene groups
      affecting Wsc1p trafficking, impaired respectively in endocytic internalization,
      multivesicular body sorting, the GARP complex, endosomal maturation/vacuolar
      fusion, and V-ATPase. Interestingly, deletion of the VPH1 gene, encoding the V(o)
      subunit of vacuolar-type H(+)-ATPase (V-ATPase), led to mis-localization of Wsc1p
      from the plasma membrane to the vacuole. In addition, disruption of other V
      ATPase subunits (vma mutants) also caused defects of Wsc1p trafficking and
      vacuolar acidification similar to those seen in the vph1Delta mutant. Moreover,
      we found that deletion of the VPS26 gene, encoding a subunit of the retromer
      complex, also caused a defect in Wsc1p recycling and mis-localization of Wsc1p to
      the vacuole. These findings clarified the previously unidentified Wsc1p recycling
      pathway and requirement of V-ATPase-dependent luminal acidification for Wsc1p
      recycling.

PMID- 24326070
TI  - Remodeling of ion channel expression may contribute to electrophysiological
      consequences caused by methamphetamine in vitro and in vivo.
AB  - Methamphetamine (MA) is a psychostimulant. MA may induce numerous cardiotoxic
      effects, leading to cardiac arrhythmias, heart failure, eventually leading to
      sudden cardiac death. The deleterious effects of methamphetamine work in tandem
      to disrupt the coordinated electrical activity of the heart and have been
      associated with life-threatening cardiac arrhythmias. Remodeling of ion channels
      is an important mechanism of arrhythmia. Although arrhythmogenic remodeling
      involves alterations in ion channel expression, it is yet unknown whether MA
      induced electrical remodeling by affecting gene expression, and whether the
      changes in protein expression are paralleled by alterations in mRNA expression.
      Our study focused on the expression of ion channels which were correlated to the
      electrical remodeling caused by MA. We used RT-PCR and western blot to assess of
      the transcript and translate levels of ion channel subunits, including Ito:
      kv1.4, kv1.7, kv3.4, kv4.2; IK1: kir2.1, kir2.2, kir2.3, kir2.4; and ICa-l:
      Ca(2+)alpha1, Ca(2+)beta, respectively. The reversible effect of these changes
      after MA withdrawal was also evaluated. MA caused decrease in mRNA and protein
      levels in all ion channel subunits in vitro and also in vivo, is at this work.
      The kv3.4 and all 4 subunits of Kir2.0 family showed significant decrease than
      the other genes. Most of the channel subunit expression started to reverse after
      MA withdrawal for 4 weeks and significantly reverse in all of the channel
      subunits after MA withdrawal for 8 weeks. We found that CACNA1C and Kir2.0 family
      showed lower recoverability than the others after MA withdrawal for 8 weeks. The
      reduction of the ion channel expression levels may be the molecular mechanism
      that mediates the electrical remodeling caused by methamphetamine.

PMID- 24326071
TI  - Uric acid induces NADPH oxidase-independent neutrophil extracellular trap
      formation.
AB  - Neutrophil extracellular traps (NETs) are composed of extracellular DNA fibers
      with antimicrobial peptides that capture and kill microbes. NETs play a critical
      role in innate host defense and in autoimmune and inflammatory diseases. While
      the mechanism of NET formation remains unclear, reactive oxygen species (ROS)
      produced via activation of NADPH oxidase (Nox) are known to be an important
      requirement. In this study, we investigated the effect of uric acid (UA) on NET
      formation. UA, a well-known ROS scavenger, was found to suppress Nox-dependent
      ROS release in a dose-dependent manner. Low concentrations of UA significantly
      inhibited Nox-dependent NET formation. However, high concentrations of UA
      unexpectedly induced, rather than inhibited, NET formation. NETs were directly
      induced by UA alone in a Nox-independent manner, as revealed by experiments using
      control neutrophils treated with ROS inhibitors or neutrophils of patients with
      chronic granulomatous disease who have a congenital defect in ROS production.
      Furthermore, we found that UA-induced NET formation was partially mediated by NF
      kappaB activation. Our study is the first to demonstrate the novel function of UA
      in NET formation and may provide insight into the management of patients with
      hyperuricemia. 

PMID- 24326072
TI  - A vertebrate model for the study of lipid binding/transfer protein function:
      conservation of OSBP-related proteins between zebrafish and human.
AB  - Oxysterol-binding protein (OSBP) and OSBP-related (ORP) or OSBP-like (OSBPL)
      proteins constitute a family of lipid-binding/transfer proteins (LTPs) present in
      eukaryotes from yeast to man. The mechanisms of ORP function have remained
      incompletely understood. However, several ORPs are present at membrane contact
      sites and act as either lipid transporters or sensors that control lipid
      metabolism, cell signaling, and vesicle transport. Zebrafish, Danio rerio, has
      gained increasing popularity as a model organism in developmental biology, human
      disease, toxicology, and drug discovery. However, LTPs in the fish are thus far
      unexplored. In this article we report a series of bioinformatic analyses showing
      that the OSBPL gene family is highly conserved between the fish and human. The
      OSBPL subfamily structure is markedly similar between the two organisms, and all
      12 human genes have orthologs, designated osbpl and located on 11 chromosomes in
      D. rerio. Interestingly, osbpl2 and osbpl3 are present as two closely related
      homologs (a and b), due to gene duplication events in the teleost lineage.
      Moreover, the domain structures of the distinct ORP proteins are almost identical
      between zebrafish and man, and molecular modeling in the present study suggests
      that ORD liganding by phosphatidylinositol-4-phosphate (PI4P) is a feature
      conserved between yeast Osh3p, human ORP3, and zebrafish Osbpl3. The present
      analysis identifies D. rerio as an attractive model to study the functions of
      ORPs in vertebrate development and metabolism. 

PMID- 24326073
TI  - The Saccharomyces cerevisiae poly(A)-binding protein is subject to multiple post
      translational modifications, including the methylation of glutamic acid.
AB  - Poly(A)-binding protein in mouse and man was recently found to be highly post
      translationally modified. Here we analysed an ortholog of this protein, Pab1 from
      Saccharomyces cerevisiae, to assess the conservation and thus likely importance
      of these modifications. Pab1 showed the presence of six sites of methylated
      glutamate, five sites of lysine acetylation, and one phosphorylation of serine.
      Many modifications on Pab1 showed either complete conservation with those on
      human or mouse PABPC1, were present on nearby residues and/or were present in the
      same domain(s). The conservation of methylated glutamate, an unusual
      modification, was of particular note and suggests a conserved function.
      Comparison of methylated glutamate sites in human, mouse and yeast poly(A)
      binding protein, along with methylation sites catalysed by CheR L-glutamyl
      protein methyltransferase from Salmonella typhimurium, revealed that the
      methylation of glutamate preferentially occurs in EE and DE motifs or other small
      regions of acidic amino acids. The conservation of methylated glutamate in the
      same protein between mouse, man and yeast suggests the presence of a eukaryotic l
      glutamyl protein methyltransferase and that the modification is of functional
      significance.

PMID- 24326074
TI  - A critical role for the regulation of Syk from agglutination to aggregation in
      human platelets.
AB  - Agglucetin, a tetrameric glycoprotein (GP) Ibalpha agonist from Formosan
      Agkistrodon acutus venom, has been characterized as an agglutination inducer in
      human washed platelets (WPs). In platelet-rich plasma (PRP), agglucetin
      dramatically elicits a biphasic response of agglutination and subsequent
      aggregation. For clarifying the intracellular signaling events from agglutination
      to aggregation in human platelets, we examined the essential signaling molecules
      involved through the detection of protein tyrosine phosphorylation (PTP). In WPs,
      an anti-GPIbalpha monoclonal antibody (mAb) AP1, but not a Src kinase inhibitor
      PP1, completely inhibited agglucetin-induced agglutination. However, PP1 but not
      AP1 had a potent suppression on platelet aggregation by a GPVI activator
      convulxin. The PTP analyses showed agglucetin alone can cause a weak pattern
      involving sequential phosphorylation of Lyn/Fyn, Syk, SLP-76 and phospholipase
      Cgamma2 (PLCgamma2). Furthermore, a Syk-selective kinase inhibitor, piceatannol,
      significantly suppressed the aggregating response in agglucetin-activated PRP.
      Analyzed by flow cytometry, the binding capacity of fluorophore-conjugated PAC-1,
      a mAb recognizing activated integrin alphaIIbbeta3, was shown to increase in
      agglucetin-stimulated platelets. Again, piceatannol but not PP1 had a
      concentration-dependent suppression on agglucetin-induced alphaIIbbeta3 exposure.
      Moreover, the formation of signalosome, including Syk, SLP-76, VAV, adhesion and
      degranulation promoting adapter protein (ADAP) and PLCgamma2, are required for
      platelet aggregation in agglucetin/fibrinogen-activated platelets. In addition,
      GPIbalpha-ligation via agglucetin can substantially promote the interactions
      between alphaIIbbeta3 and fibrinogen. Therefore, the signal pathway of
      Lyn/Fyn/Syk/SLP-76/ADAP/VAV/PLCgamma2/PKC is sufficient to trigger platelet
      aggregation in agglucetin/fibrinogen-pretreated platelets. Importantly, Syk may
      function as a major regulator for the response from GPIbalpha-initiated
      agglutination to integrin alphaIIbbeta3-dependent aggregation in human platelets.

PMID- 24326075
TI  - Cognitive behavioral therapy and pharmacotherapy for anxiety: treatment
      preferences and credibility among pregnant and non-pregnant women.
AB  - BACKGROUND: Relatively little is known about women's anxiety-related treatment
      preferences and no studies have examined potential differences between pregnant
      versus non-pregnant women. Treatment credibility and willingness are particularly
      important to understand regarding exposure-based cognitive behavioral therapy
      (CBT) and pharmacotherapy, the leading evidence-based treatments. METHODS: A
      large U.S. sample of pregnant (n = 377) and matched non-pregnant (n = 399) women
      (total N = 776) rated overall treatment preferences and treatment credibility,
      concerns, and willingness to have CBT and pharmacotherapy if suffering from
      anxiety. RESULTS: Women preferred anxiety-related treatment that included
      psychotherapy. Preference for psychotherapy alone was stronger among pregnant
      (74%) than non-pregnant (47%) women, p < .001. In response to treatment
      descriptions, both groups rated CBT more favorably than pharmacotherapy on
      treatment willingness, credibility, and concerns, ps < .001, with the magnitude
      of this preference significantly greater among pregnant than non-pregnant women,
      ps < .001. Pregnancy status was unrelated to CBT ratings. Treatment credibility
      and to a lesser extent total concerns mediated the relationship between pregnancy
      status and pharmacotherapy willingness. CONCLUSIONS: Non-pregnant and especially
      pregnant women rated exposure-based CBT for anxiety more favorably than
      pharmacotherapy. Pregnancy status predicted general treatment preferences and
      pharmacotherapy, but not CBT, ratings.

PMID- 24326076
TI  - Poor health and loneliness in later life: the role of depressive symptoms, social
      resources, and rural environments.
AB  - OBJECTIVES: We draw on cognitive discrepancy theory to hypothesize and test a
      pathway from poor health to loneliness in later life. We hypothesize that poor
      health will have a negative influence on social participation and social
      resources, and these factors will mediate between health and loneliness. We
      hypothesize that rural environments will amplify any difficulties associated with
      social participation or accessing social resources and that depression will
      moderate how intensely people react to levels of social contact and support.
      METHODS: We conceptualize a mediation model and a moderated-mediation model.
      Nationally representative data on older people living in the Republic of Ireland
      are used to validate the hypothesized pathways. RESULTS: In the mediation model,
      health has a significant indirect effect on loneliness through the mediating
      variables social resources and social participation. In the moderated-mediation
      model, rurality moderates the pathway between health and social resources but not
      social participation. Depressive symptoms moderate the effect of social resources
      on loneliness but not social participation. DISCUSSION: The results provide
      further credence to cognitive discrepancy theory, suggesting that depressive
      symptoms influence cognitive processes, interfering with judgments about the
      adequacy of social interaction. The theory is extended by demonstrating the
      impact of the environment on loneliness.

PMID- 24326078
TI  - Variety is the Spice of Life: A Microlongitudinal Study Examining Age Differences
      in Intraindividual Variability in Daily Activities in Relation to Sleep Outcomes.
AB  - OBJECTIVE: The relative importance of mean timing of daily activities versus
      intraindividual variability in the timing of daily activities in relation to
      health outcomes such as sleep has yet to be established. Furthermore, age-related
      changes in sleep could affect this relationship. The study objective was to
      examine the extent that intraindividual variability in the timing of daily
      activities is associated with sleep outcomes in younger and older adults.
      MEASURES: A microlongitudinal observational study design was used with 14
      consecutive days of diaries in community-dwelling younger and older adults. 50
      younger and 50 older adults completed daily assessments of activities and sleep.
      Three activities (going outside, starting work, and eating dinner) and 5 sleep
      (sleep onset latency, wake time after sleep onset, number of awakenings, total
      sleep time, and sleep quality rating) variables were used in the analyses.
      RESULTS: Hierarchical regressions revealed variability in the timing of daily
      activities significantly predicted sleep, beyond mean timing of activities, for 4
      of 6 models. Results differed depending on the type of activity and age group.
      DISCUSSION: Intraindividual variability, not mean timing of daily activities,
      best-predicted sleep outcomes. Variability was associated with positive sleep
      outcomes for older, but not younger adults.

PMID- 24326077
TI  - Sleep Architecture and Mental Health Among Community-Dwelling Older Men.
AB  - OBJECTIVES: To investigate the association of mood and anxiety symptoms with
      sleep architecture (the distribution of sleep stages) in community-dwelling older
      men. METHOD: We used in-home unattended polysomnography to measure sleep
      architecture in older men. Men were categorized into 4 mental health categories:
      (a) significant depressive symptoms only (DEP+ only, Geriatric Depression Scale
      >= 6), (b) significant anxiety symptoms only (ANX+ only, Goldberg Anxiety Scale
      >= 5), (c) significant depressive and anxiety symptoms (DEP+/ANX+), or (d) no
      significant depressive or anxiety symptoms (DEP-/ANX-). RESULTS: Compared with
      men without clinically significant symptomology, men with depressive symptoms
      spent a higher percentage of time in Stage 2 sleep (65.42% DEP+ only vs 62.47%
      DEP-/ANX-, p = .003) and a lower percentage of time in rapid eye movement sleep
      (17.05% DEP+ only vs 19.44% DEP-/ANX-, p = .0005). These differences persisted
      after adjustment for demographic/lifestyle characteristics, medical conditions,
      medications, and sleep disturbances, and after excluding participants using
      psychotropic medications. The sleep architecture of ANX+ or DEP+/ANX+ men did not
      differ from asymptomatic men. DISCUSSION: Depressed mood in older adults may be
      associated with accelerated age-related changes in sleep architecture.
      Longitudinal community-based studies using diagnostic measures are needed to
      further clarify relationships among common mental disorders, aging, and sleep.

PMID- 24326079
TI  - "Gratitude is with me all the time": how gratitude relates to wisdom.
AB  - OBJECTIVES: This study investigated the relationship of gratitude to wisdom. Both
      constructs are conceptually related to self-reflectivity, but they differ in
      their emphasis on extrapersonal resources. Previous wisdom research has focused
      mainly on intrapersonal capacities. METHOD: In Study 1, 47 wisdom nominees and 47
      control participants were interviewed about their most difficult and best life
      event and filled out a questionnaire on sources of gratitude. Study 2 was a
      quantitative study (N = 443) of the relationship between a wisdom scale and scale
      measures and individual sources of gratitude. RESULTS: Significantly more wisdom
      nominees expressed feelings of gratitude spontaneously in their interview. Wisdom
      nominees reported gratitude for their life in general, religion, and partner more
      often than control participants. In Study 2, wisdom was related to all gratitude
      scales and to similar sources of gratitude as in Study 1. Both studies found
      gender differences in gratitude but not wisdom. DISCUSSION: Two important
      implications of these findings are that wisdom entails an appreciation of life
      and its experiences, especially the growth opportunities that may result from
      negative events, and that there may be substantial differences between male and
      female pathways to wisdom.

PMID- 24326080
TI  - Meso-Rex bypass--a procedure to cure prehepatic portal hypertension: the insight
      and the inside.

PMID- 24326081
TI  - Molecular identification of zoonotic and livestock-specific Giardia-species in
      faecal samples of calves in Southern Germany.
AB  - BACKGROUND: Giardia-infection in cattle is often subclinical or asymptomatic, but
      it can also cause diarrhoea. The livestock-specific species Giardia bovis is the
      most frequently observed in cattle, however, the two zoonotic species Giardia
      duodenalis and Giardia enterica have also been found. Therefore calves are
      thought to be of public health significance. The aim of this study was to obtain
      current data about the frequency of the different Giardia-species in calves in
      Southern Germany. FINDINGS: Faecal samples of calves (diarrhoeic and healthy) in
      Southern Germany, diagnosed Giardia-positive by microscopy, were characterised by
      multi-locus PCR and sequencing.Of 152 microscopically Giardia-positive samples
      110 (72.4%) were positive by PCR and successfully sequenced. G. bovis (Assemblage
      E) was detected in 101/110 (91.8%) PCR-positive samples, whilst G. duodenalis
      (Assemblage A) was detected in 8/110 (7.3%) samples and a mixed infection with G.
      duodenalis and G. bovis (Assemblage A+E) was identified in 1/110 (0.9%) samples.
      The sub-genotypes A1, E2 and E3 were identified with the beta-giardin and the
      glutamate dehydrogenase genes. In the majority of diarrhoeic faecal samples a co
      infection with Cryptosporidium spp. or Eimeria spp. was present, however, there
      were some in which G. bovis was the only protozoan pathogen found. CONCLUSIONS:
      The results suggest that there is potentially a risk for animal handlers as
      calves in Southern Germany are, at a low percentage, infected with the zoonotic
      species G. duodenalis. In addition, it was found that G. bovis was the only
      pathogen identified in some samples of diarrhoeic calves, indicating that this
      parasite may be a contributing factor to diarrhoea in calves.

PMID- 24326082
TI  - Quality of criminal responsibility reports submitted to the Hawaii judiciary.
AB  - This paper is the third in a series of research reports on quality of forensic
      mental health evaluations submitted to the Hawaii judiciary. Previous studies
      examined quality of reports assessing competency to stand trial (CST) and post
      acquittal conditional release, in felony defendants undergoing court-ordered
      examinations. Utilizing a 44-item quality coding instrument, this study examined
      quality of criminal responsibility reports in a sample of 150 forensic mental
      health evaluations conducted between 2006 and 2010 by court-appointed panels.
      Raters attained high levels of agreement in training and quality coding. Similar
      to the previous studies, overall quality of reports was mediocre, falling below
      the .80 quality criterion score for report elements, regardless of evaluator
      professional identification or employment status. Level of agreement between
      evaluators and judicial sanity determinations was "fair" using Cicchetti's (1994)
      standards for interpretation of intra-class correlations. Level of agreement was
      lower than previously published findings for CST reports and better than
      conditional release reports. Reasons for mediocre report quality and "fair" inter
      rater agreement are discussed, including the fact that criminal responsibility
      evaluations are complex, retrospective in nature, and involve significant degrees
      of inference. In contrast to CST evaluations, assessment of criminal
      responsibility involves a mental state at the time of the offense evaluation.
      Threats to reliability in forensic reports are discussed. Suggestions for
      improvement of report quality are proffered, including standardization of
      procedures and report format and use of forensic assessment instruments. 

PMID- 24326083
TI  - Anaerobic fermentation of biogas liquid pretreated maize straw by rumen
      microorganisms in vitro.
AB  - This study intended to investigate the effect of pretreatment of maize straw with
      biogas liquid on followed fermentation by rumen microorganisms in vitro. The
      multiple effects including treated time, temperature and dosage of biogas liquid
      in pretreatment on the followed fermentation performance were analyzed by
      orthogonal array. The optimum conditions of pretreatment were 9days, 25 degrees C
      and 50% (v/w) dosage of biogas liquid, which were indicated by the corresponding
      crystallinity index, dry matter digestibility (DMD) and acetate limiting-step
      concentration were 57.5%, 73.76% and 1756mg/L, respectively. The ordering
      sequence of the influential factors for pretreatment was treated time >
      temperature > dosage of biogas liquid. The results of fermentation showed that
      the maize straw pretreated by biogas liquid was an efficient and economic
      pretreatment method of maize straw. 

PMID- 24326084
TI  - Grammatical number agreement processing using the visual half-field paradigm: an
      event-related brain potential study.
AB  - Despite indications in the split-brain and lesion literatures that the right
      hemisphere is capable of some syntactic analysis, few studies have investigated
      right hemisphere contributions to syntactic processing in people with intact
      brains. Here we used the visual half-field paradigm in healthy adults to examine
      each hemisphere's processing of correct and incorrect grammatical number
      agreement marked either lexically, e.g., antecedent/reflexive pronoun ("The
      grateful niece asked herself/*themselves...") or morphologically, e.g.,
      subject/verb ("Industrial scientists develop/*develops..."). For reflexives,
      response times and accuracy of grammaticality decisions suggested similar
      processing regardless of visual field of presentation. In the subject/verb
      condition, we observed similar response times and accuracies for central and
      right visual field (RVF) presentations. For left visual field (LVF) presentation,
      response times were longer and accuracy rates were reduced relative to RVF
      presentation. An event-related brain potential (ERP) study using the same
      materials revealed similar ERP responses to the reflexive pronouns in the two
      visual fields, but very different ERP effects to the subject/verb violations. For
      lexically marked violations on reflexives, P600 was elicited by stimuli in both
      the LVF and RVF; for morphologically marked violations on verbs, P600 was
      elicited only by RVF stimuli. These data suggest that both hemispheres can
      process lexically marked pronoun agreement violations, and do so in a similar
      fashion. Morphologically marked subject/verb agreement errors, however, showed a
      distinct LH advantage. 

PMID- 24326086
TI  - Editorial: changes to the masthead.

PMID- 24326085
TI  - The effect of excess fluid balance on the mortality rate of surgical patients: a
      multicenter prospective study.
AB  - INTRODUCTION: In some studies including small populations of patients undergoing
      specific surgery, an intraoperative liberal infusion of fluids was associated
      with increasing morbidity when compared to restrictive strategies. Therefore, to
      evaluate the role of excessive fluid infusion in a general population with high
      risk surgery is very important. The aim of this study was to evaluate the impact
      of intraoperative fluid balance on the postoperative organ dysfunction, infection
      and mortality rate. METHODS: We conducted a prospective cohort study during one
      year in four ICUs from three tertiary hospitals, which included patients aged 18
      years or more who required postoperative ICU after undergoing major surgery.
      Patients who underwent palliative surgery and whose fluid balance could change in
      outcome were excluded. The calculation of fluid balance was based on preoperative
      fasting, insensible losses from surgeries and urine output minus fluid
      replacement intraoperatively. RESULTS: The study included 479 patients. Mean age
      was 61.2 +/- 17.0 years and 8.8% of patients died at the hospital during the
      study. The median duration of surgery was 4.0 (3.2 to 5.5) h and the value of the
      Simplified Acute Physiology Score (SAPS) 3 score was 41.8 +/- 14.5. Comparing
      survivors and non-survivors, the intraoperative fluid balance from non-survivors
      was higher (1,950 (1,400 to 3,400) mL vs. 1,400 (1,000 to 1,600) mL, P <0.001).
      Patients with fluid balance above 2,000 mL intraoperatively had a longer ICU stay
      (4.0 (3.0 to 8.0) vs. 3.0 (2.0 to 6.0), P <0.001) and higher incidence of
      infectious (41.9% vs. 25.9%, P = 0.001), neurological (46.2% vs. 13.2%, P
      <0.001), cardiovascular (63.2% vs. 39.6%, P <0.001) and respiratory complications
      (34.3% vs. 11.6%, P <0.001). In multivariate analysis, the fluid balance was an
      independent factor for death (OR per 100 mL = 1.024; P = 0.006; 95% CI 1.007 to
      1.041). CONCLUSIONS: Patients with excessive intraoperative fluid balance have
      more ICU complications and higher hospital mortality.

PMID- 24326087
TI  - Intranasal neuropeptide Y reverses anxiety and depressive-like behavior impaired
      by single prolonged stress PTSD model.
AB  - PTSD is a debilitating neuropsychiatric disorder and many patients do not respond
      sufficiently to current treatments. Neuropeptide Y (NPY) is suggested to provide
      resilience to the development of PTSD and co-morbid depression. Injections of NPY
      to the rodent brain are anxiolytic. Recently we showed that intranasal delivery
      of NPY to rats before or immediately after exposure to single prolonged stress
      (SPS) animal model of PTSD prevented development of many biochemical and
      behavioral symptoms of PTSD, indicating its prophylactic potential. Here, we
      investigated whether intranasal NPY might provide benefits once symptoms have
      already developed. One week after exposure to SPS stressors, animals were given
      intranasal NPY or vehicle and tested on elevated plus maze 2h or 2 days later.
      The NPY treated rats had lower anxiety-like behavior than vehicle treated rats as
      indicated by more entries into open arms and fewer into closed arms, lower
      anxiety index, higher risk assessment and unprotected head dips and reduced
      grooming time. Their anxiety index was similar to that of unstressed controls. On
      most of these variables there was no effect of time interval and rats displayed
      similar overall changes 2h or 2 days after the infusion. Moreover, intranasal NPY
      led to reduced depressive-like behavior, assessed by forced swim test. Thus,
      intranasal NPY reversed several behavioral impairments triggered by the traumatic
      stress of SPS and has potential for non-invasive PTSD therapeutic intervention. 

PMID- 24326089
TI  - [Facial follicular mucinosis in childhood].

PMID- 24326088
TI  - Treatment of obstructive sleep apnea with oral appliances.
AB  - BACKGROUND: The purpose of this study was to evaluate the effectiveness of
      mandibular advancement devices (MADs) for treatment of obstructive sleep apnea
      syndrome (OSAS) compared with the results obtained with a placebo device in
      accordance with the following indicators: apnea hypopnea index (AHI) per hour of
      sleep, apnea index (AI) per hour of sleep, mean oxyhemoglobin saturation, sleep
      efficiency, and percentage of rapid eye movement (REM) sleep. METHODS: This is a
      controlled, prospective longitudinal study with a follow-up time of 10.5 months.
      Nineteen patients (8 females and 11 males) with mean age 48.6 years (SD 9.6) were
      selected for the study. The sample was randomized in terms of device use, and the
      evaluation design was double blind. A total of 57 polysomnography tests were
      studied (at baseline, after the use of a MAD, and after the use of placebo). The
      following variables were assessed: AHI, AI, mean oxyhemoglobin saturation,
      percentage of REM sleep, and sleep efficiency. Wilcoxon and Mann-Whitney tests
      were used for evaluating data (p<0.05). RESULTS: Reductions from 16.3 to 11.7 in
      AHI and from 5.7 to 3.8 in AI were observed after MAD use. During the use of
      placebo, AHI increased from 16.3 to 19.6, and AI from 5.7 to 7.5. The other
      indexes showed no statistically significant differences. CONCLUSIONS: Treatment
      with oral appliances, i.e., MADs, can be an effective alternative for mild and
      medium-to-moderate OSAS, but requires strict monitoring due to differences in
      individual response to this therapy.

PMID- 24326090
TI  - Mechanisms of Class II correction induced by the crown Herbst appliance as a
      single-phase Class II therapy: 1 year follow-up.
AB  - BACKGROUND: The objective of this study is to evaluate the skeletal and
      dentoalveolar effects of the crown Herbst appliance used alone for a single phase
      of therapy followed by a 1-year observation period. METHODS: Forty patients (mean
      age 13.6+/-1.3 years) with a stable Class I occlusion 1 year following the
      treatment with the crown Herbst appliance were selected from a prospective sample
      of 180 consecutively treated Class II patients. No other appliances were used
      during treatment or during the follow-up period. The dentoskeletal changes were
      compared with a matched sample of untreated Class II subjects (mean age 13.9+/
      1.6 years). Lateral cephalograms were taken before treatment, after Herbst
      treatment (1 year), and after 1-year follow-up. Overcorrection was avoided
      intentionally. RESULTS: Treatment produced an increase in mandibular length, a
      decrease in ANB angle, and a restriction in the vertical growth of posterior
      maxilla. The maxillary molars moved backward and tipped distally. The lower
      incisors proclined markedly, and the upper incisors became retroclined. During
      the follow-up period, the changes primarily were dentoalveolar in nature, with
      marked rebound of the upper molars and lower incisors, resulting in some
      increases in overbite and overjet. CONCLUSIONS: The occlusal correction of Class
      II malocclusion observed 1 year after the crown Herbst appliance as a single
      phase therapy was achieved primary due to the dentoalveolar changes and only
      limited skeletal change occurred.

PMID- 24326091
TI  - Versatile on-resin synthesis of high mannose glycosylated asparagine with
      functional handles.
AB  - Here we present a synthetic route for solid phase synthesis of N-linked
      glycoconjugates containing high mannose oligosaccharides which allows the
      incorporation of useful functional handles on the N-terminus of asparagine. In
      this strategy, the C-terminus of an Fmoc protected aspartic acid residue is first
      attached to a solid phase support. The side chain of aspartic acid is protected
      by a 2-phenylisopropyl protecting group, which allows selective deprotection for
      the introduction of glycosylation. By using a convergent on-resin glycosylamine
      coupling strategy, an N-glycosidic linkage is successfully formed on the free
      side chain of the resin bound aspartic acid with a large high mannose
      oligosaccharide, Man8GlcNAc2, to yield N-linked high mannose glycosylated
      asparagine. The use of on-resin glycosylamine coupling provides excellent
      glycosylation yield, can be applied to couple other types of oligosaccharides,
      and also makes it possible to recover excess oligosaccharides conveniently after
      the on-resin coupling reaction. Useful functional handles including an alkene (p
      vinylbenzoic acid), an alkyne (4-pentynoic acid), biotin, and 5
      carboxyfluorescein are then conjugated onto the N-terminal amine of asparagine on
      resin after the removal of the Fmoc protecting group. In this way, useful
      functional handles are introduced onto the glycosylated asparagine while
      maintaining the structural integrity of the reducing end of the oligosaccharide.
      The asparagine side chain also serves as a linker between the glycan and the
      functional group and preserves the native presentation of N-linked glycan which
      may aid in biochemical and structural studies. As an example of a biochemical
      study using functionalized high mannose glycosylated asparagine, a fluorescence
      polarization assay has been utilized to study the binding of the lectin
      Concanavalin A (ConA) using 5-carboxyfluorescein labeled high mannose
      glycosylated asparagine. 

PMID- 24326092
TI  - The association between chemosensitivity and Pgp, GST-pi and Topo II expression
      in gastric cancer.
AB  - BACKGROUND: To investigate the relationship between P-glycoprotein (Pgp),
      glutathione S-transferase pi (GST-pi) and topoisomerase II (Topo II) expression
      and human gastric cancer chemoresistance in vitro. METHODS: Primary single-cell
      suspensions were prepared from fresh specimens of primary gastric cancer and
      exposed to hydroxycamptothecin (HCPT), cisplatin (CDDP), 5-fluorouracil (5-FU),
      adriamycin (ADM) and mitomycin (MMC) for 48 h. Cell metabolic activity and rate
      of inhibition were evaluated using tetrazolium (MTT) assay. Pgp, GST-pi and Topo
      II expression was determined in gastric carcinoma tissue samples using
      immunohistochemistry. RESULTS: Chemosensitivity of the gastric cancer cells
      varied; the rates of inhibition of cells exposed to HCPT, CDDP and 5-FU were
      significantly higher than that of cells exposed to ADM and MMC (p < 0.05).
      Gastric cancer cells with Pgp expression were resistant to ADM and HCPT (p =
      0.008 and p = 0.011, respectively). Cells resistant to 5-FU, CDDP and MMC had
      significantly higher GST-pi expression (p < 0.05). Topo II expression was
      significantly lower in cells resistant to HCPT, ADM and MMC (p < 0.05). Pgp and
      GST-pi expression may contribute to primary resistance of gastric cancer cells to
      some chemotherapeutic drugs, while Topo II expression may indicate HCPT, ADM and
      MMC sensitivity. CONCLUSIONS: Pgp, GST-pi and Topo II detection and the MTT assay
      could be used as predictors in chemotherapeutic drug administration and for
      identifying drug resistance in gastric carcinoma. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3448329111142964.

PMID- 24326093
TI  - Relationship between vertical facial patterns and dental arch form in class II
      malocclusion.
AB  - BACKGROUND: The purpose of this study is to evaluate the relationship between
      dental arch form and the vertical facial pattern determined by the angle between
      the mandibular plane and the anterior cranial base (Sella-nasion/mandibular plane
      angle (SN-MP)) in skeletal class II untreated patients. METHODS: A sample of 73
      Caucasians patients with untreated skeletal class II in permanent dentition was
      divided into three groups according to the values of the angle SN-MP. An
      evaluation of the arch form was performed by angular and linear relation values
      on each patient. Regression analysis was used to determine the statistical
      significance of the relationships between SN-MP angle and dental arch form. The
      differences among the three groups were analyzed for significance using a
      variance analysis. RESULTS: A decrease of the upper arch transversal diameters in
      high SN-MP angle patients and an increase in low angle SN-MP ones (P<0.05) were
      shown. Result analysis showed a change in upper arch shape, with a smaller
      intercanine width in patients with high SN-MP angle and a greater one in low
      angle patients. As SN-MP angle increased, the upper arch form tended to be
      narrower. No statistically significant difference in mandibular arch form among
      the three groups was found, except the angle value related to incisors position.
      CONCLUSIONS: The results showed the association between the upper dental arch
      form and the vertical facial pattern. On the contrary, the lower arch form was
      not related to the mandibular divergence.

PMID- 24326094
TI  - Neuroprotective effect of chondroitinase ABC on primary and secondary brain
      injury after stroke in hypertensive rats.
AB  - Focal cerebral infarction causes secondary damage in the ipsilateral
      ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs)
      are a family of putative inhibitory components, and its degradation by
      chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study
      investigated the role of ChABC in the primary and secondary injury post stroke in
      hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle
      cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct
      infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was
      evaluated by a modified neurologic severity score. Neurons were counted in the
      peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl
      staining and NeuN labeling. The expressions of CSPGs, growth-associated protein
      43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or
      Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated
      CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both
      the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as
      augmented axonal growth and synaptic plasticity, eventually improving overall
      neurological function. The study demonstrated that intra-infarct ChABC infusion
      could salvage the brain from both primary and secondary injury by the
      intervention on the neuroinhibitory environment post focal cerebral infarction.

PMID- 24326095
TI  - Effects of cortical activations on enhancement of handgrip force during teeth
      clenching: an fMRI study.
AB  - We assessed the effect of teeth clenching on handgrip force behaviorally, and
      investigated cortical activity during the occurrence of facilitatory effects
      using functional magnetic resonance imaging (fMRI). Twenty-three participants
      were assessed as to whether they had habitual teeth clenching during maximal
      voluntary contraction (MVC) exertion, and 21 of them were identified to have such
      a habit. For those participants, behavioral testing showed that MVC with
      clenching was greater compared with without clenching (approximately 108% greater
      on average). Next, cortical activity was measured under gripping with clenching
      (GwC), gripping without clenching (GwoC), and teeth clenching (C) conditions. We
      found that the activity of the hand region in primary motor cortex (M1),
      cingulate motor area/supplementary motor area (CMA/SMA) and anterior cerebellum
      (AC) was greater in contrast of GwC vs. (GwoC+C). Furthermore, significant
      correlation was observed between the increasing ratio of the handgrip force and
      the % signal change in the hand region of M1 and AC, but not in CMA/SMA. These
      results suggest that the activation in the hand region of M1 and AC may
      facilitate the spinal motoneurons, and the activation in the hand region in M1 by
      clenching may be due to a signal from CMA/SMA. 

PMID- 24326096
TI  - Co-infection of Borrelia burgdorferi sensu lato and Rickettsia species in ticks
      and in an erythema migrans patient.
AB  - BACKGROUND: Lyme borreliosis is the most prevalent tick-borne disease in Europe.
      Ixodes ricinus also carries other pathogenic bacteria, but corresponding human
      diseases are rarely reported. Here, we compared the exposure to Rickettsia
      helvetica and Rickettsia monacensis with that to Lyme borreliosis spirochetes. We
      assumed that their exposure corresponds to their infection rate in questing I.
      ricinus. FINDINGS: Three Rickettsia species were detected in ticks with a total
      prevalence of 7.9%, of which the majority was R. helvetica (78%) and R.
      monacensis (21%). From the same geographic area, skin biopsies of erythema
      migrans patients were investigated for possible co-infections with Rickettsia
      spp.. Forty-seven out of 67 skin biopsies were PCR positive for Borrelia
      burgdorferi s.l. and one sample was positive for R. monacensis. The Borrelia
      genospecies from the R. monacensis positive patient was identified as Borrelia
      afzelii. The patient did not show any symptoms associated with rickettsiosis.
      CONCLUSIONS: Co-infections of I. ricinus with Rickettsia spp. and B. burgdorferi
      s.l. were as high as expected from the individual prevalence of both pathogens.
      Co-infection rate in erythema migrans patients corresponded well with tick
      infection rates. To our knowledge, this is the first reported co-infection of B.
      afzelii and R. monacensis.

PMID- 24326097
TI  - Primary and secondary restraints of human and ovine knees for simulated in vivo
      gait kinematics.
AB  - Knee soft tissue structures are frequently injured, leading to the development of
      osteoarthritis even with treatment. Understanding how these structures contribute
      to knee function during activities of daily living (ADLs) is crucial in creating
      more effective treatments. This study was designed to determine the role of
      different knee structures during a simulated ADL in both human knees and ovine
      stifle joints. A six degree-of-freedom robot was used to reproduce each species'
      in vivo gait while measuring three-dimensional joint forces and torques. Using a
      semi-randomized selective cutting method, we determined the primary and secondary
      structures contributing to the forces and torques along and about each anatomical
      axis. In both species, the bony interaction, ACL, and medial meniscus provided
      most of the force contributions during stance, whereas the ovine MCL, human bone,
      and ACLs of both species were the key contributors during swing. This study
      contributes to our overarching goal of establishing functional tissue engineering
      parameters for knee structures by further validating biomechanical similarities
      between the ovine model and the human to provide a platform for measuring
      biomechanics during an in vivo ADL. These parameters will be used to develop more
      effective treatments for knee injuries to reduce or eliminate the incidence of
      osteoarthritis. 

PMID- 24326098
TI  - Hydrostatic pressure decreases membrane fluidity and lipid desaturase expression
      in chondrocyte progenitor cells.
AB  - Membrane biomechanical properties are critical in modulating nutrient and
      metabolite exchange as well as signal transduction. Biological membranes are
      predominantly composed of lipids, cholesterol and proteins, and their fluidity is
      tightly regulated by cholesterol and lipid desaturases. To determine whether such
      membrane fluidity regulation occurred in mammalian cells under pressure, we
      investigated the effects of pressure on membrane lipid order of mouse
      chondrogenic ATDC5 cells and desaturase gene expression. Hydrostatic pressure
      linearly increased membrane lipid packing and simultaneously repressed lipid
      desaturase gene expression. We also showed that cholesterol mimicked and
      cholesterol depletion reversed those effects, suggesting that desaturase gene
      expression was controlled by the membrane physical state itself. This study
      demonstrates a new effect of hydrostatic pressure on mammalian cells and may help
      to identify the molecular mechanisms involved in hydrostatic pressure sensing in
      chondrocytes. 

PMID- 24326099
TI  - Determination of the tensile mechanical properties of the segmented mitral valve
      annulus.
AB  - The mitral valve annulus is a complex and irregular component of the mitral valve
      apparatus, serving both a structural and sphincteric role. We have sought to
      determine the mechanical properties of the mitral valve annulus segmentally.
      Twenty porcine hearts were dissected to isolate the annulus. The annulus was
      segmented into four sections: anterior, posterior, and left and right commissural
      sections. Ten of these were tensile tested to failure as control samples. The
      remaining ten were digested in order to fully isolate the annulus from the
      myocardium, and subsequently tensile tested to failure. Histological samples of
      each segment were analysed to determine collagen/annular content. Whole segments
      of muscular annulus were tensile tested to failure; the stress and strain at
      failure and location of failure were determined in these larger specimens. Our
      results demonstrated that the anterior annulus is stiffer than the posterior
      segment by a factor of approximately 27 at a 2% strain level, and approximately
      13 at a 6% strain. There is a trend in the results that identifies that the
      muscular annulus is stiffest at the right commissural segment, while the
      posterior segment tends to be the least stiff. The stiffness of the samples can
      be correlated with the area associated with the dense collagen annulus using
      histological analysis. Finally, the weakest section of the mitral valve annulus
      was identified as the intersection of the right commissural segment and the
      posterior segment. 

PMID- 24326100
TI  - Re: On the accuracy of the Head Impact Telemetry (HIT) system used in football
      helmets.

PMID- 24326101
TI  - Initial impact of tailored web-based messages about cigarette smoke and breast
      cancer risk on boys' and girls' risk perceptions and information seeking:
      randomized controlled trial.
AB  - BACKGROUND: Recent evidence indicates a causal link between both active smoking
      and secondhand smoke (SHS) exposure and breast cancer (BC). OBJECTIVE: The
      objective of the present study was to evaluate the initial reactions of girls and
      boys to tailored Web-based messages that describe the relationship between SHS
      and BC, using a parallel, single-blinded cluster randomized controlled trial.
      METHODS: This trial was nested within a cycle of an ongoing longitudinal study of
      1498 students from 74 secondary schools. Self-reported assessments were used to
      evaluate the impact of study messages on participants' risk perception and
      interest in obtaining additional information after participants were randomized
      by schools to control or intervention groups. The intervention group received a
      tailored visual message (based on gender and Aboriginal status) about BC and
      tobacco smoke. The control group received a standard visual message about smoking
      and cancer. RESULTS: SHS exposure was identified as a BC risk factor by 380/1488
      (25.54%) participants, during the preintervention analysis. Compared to the
      female participants in the control group (491/839, 58.5%), girls who received the
      intervention (339/649, 52.2%) were 14% more likely to agree that exposure to SHS
      increased their BC risk (relative risk [RR] 1.14, 95% CI 1.07-1.21). Nonsmoking
      girls who received the intervention were 14% more likely to agree that starting
      smoking would increase their BC risk (RR 1.14, 95% CI 1.07-1.21). Compared to the
      male participants in control group (348/839, 41.5%), boys who received the
      intervention (310/649, 47.8%) were 10% more likely to agree that girls' exposure
      to SHS increased their BC risk (RR 1.10, 95% CI 1.02-1.18). Compared to controls,
      girls who received the intervention were 52% more likely to request additional
      information about SHS and BC (RR 1.52, 95% CI 1.12-2.06). CONCLUSIONS: Brief
      gender-sensitive messages delivered via the Internet have the potential to
      increase awareness and to stimulate information seeking about the risk for BC
      associated with SHS.

PMID- 24326102
TI  - Potential predictive values of inflammatory biomarkers for stroke rehabilitation
      outcomes.

PMID- 24326104
TI  - Mutations of cytochrome c identified in patients with thrombocytopenia THC4
      affect both apoptosis and cellular bioenergetics.
AB  - Inherited thrombocytopenias are heterogeneous diseases caused by at least 20
      genes playing different role in the processes of megakaryopoiesis and platelet
      production. Some forms, such as thrombocytopenia 4 (THC4), are very rare and not
      well characterized. THC4 is an autosomal dominant mild thrombocytopenia described
      in only one large family from New Zealand and due to a mutation (G41S) of the
      somatic isoform of the cytochrome c (CYCS) gene. We report a novel CYCS mutation
      (Y48H) in patients from an Italian family. Similar to individuals carrying G41S,
      they have platelets of normal size and morphology, which are only partially
      reduced in number, but no prolonged bleeding episodes. In order to determine the
      pathogenetic consequences of Y48H, we studied the effects of the two CYCS
      mutations in yeast and mouse cellular models. In both cases, we found reduction
      of respiratory level and increased apoptotic rate, supporting the pathogenetic
      role of CYCS in thrombocytopenia.

PMID- 24326103
TI  - In vivo functions of Drp1: lessons learned from yeast genetics and mouse
      knockouts.
AB  - Mitochondria grow, divide, and fuse in cells. Mitochondrial division is critical
      for the maintenance of the structure and function of mitochondria. Alterations in
      this process have been linked to many human diseases, including peripheral
      neuropathies and aging-related neurological disorders. In this review, we discuss
      recent progress in mitochondrial division by focusing on molecular and in vivo
      analyses of the evolutionarily conserved, central component of mitochondrial
      division, dynamin-related protein 1 (Drp1), in the yeast and mouse model
      organisms.

PMID- 24326105
TI  - An easy method of attachment to an impacted canine.
AB  - BACKGROUND: Since many years, various bonding attachments have been used as a
      mode of traction for surgically exposed impacted teeth. It has always been a
      challenge to select an attachment considering predictability of the bonded
      attachment, mucogingival and periodontal conditions of the overlying tissues, and
      additional inventory requirement. METHODS: A 0.010-in. stainless steel ligature
      wire with eyelets at one end and spiral twisted at the other end was made and
      used as an attachment to guide surgically exposed impacted canine. RESULTS:
      Orthodontic guided eruption of an impacted canine of a 16-year-old patient using
      this simple attachment with 1-year follow-up illustrates adequate amount of
      attached gingiva. CONCLUSIONS: Ligature wire attachment is a simple inexpensive
      attachment that can be custom made without any need for additional inventory,
      besides being more comfortable to patients.

PMID- 24326106
TI  - RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal
      neovascularization secondary to pathologic myopia.
AB  - OBJECTIVE: To compare the efficacy and safety of ranibizumab 0.5 mg, guided by
      visual acuity (VA) stabilization or disease activity criteria, versus verteporfin
      photodynamic therapy (vPDT) in patients with visual impairment due to myopic
      choroidal neovascularization (CNV). DESIGN: Phase III, 12-month, randomized,
      double-masked, multicenter, active-controlled study. PARTICIPANTS: Patients (N =
      277) with visual impairment due to myopic CNV. METHODS: Patients were randomized
      to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA
      stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as
      needed guided by disease activity criteria (group II, n=116); or vPDT on day 1
      and disease activity treated with ranibizumab or vPDT at investigators'
      discretion from month 3 (group III, n = 55). MAIN OUTCOME MEASURES: Mean average
      best-corrected visual acuity (BCVA) change from baseline to month 1 through
      months 3 (primary) and 6, mean BCVA change and safety over 12 months. RESULTS:
      Ranibizumab treatment in groups I and II was superior to vPDT based on mean
      average BCVA change from baseline to month 1 through month 3 (group I: +10.5,
      group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study
      [ETDRS] letters; both P<0.0001). Ranibizumab treatment guided by disease activity
      was noninferior to VA stabilization-guided retreatment based on mean average BCVA
      change from baseline to month 1 through month 6 (group II: +11.7 vs. group I:
      +11.9 ETDRS letters; P<0.00001). Mean BCVA change from baseline to month 12 was
      +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month
      12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients
      received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab
      injections over 12 months. No deaths or cases of endophthalmitis and myocardial
      infarction occurred. CONCLUSIONS: Ranibizumab treatment, irrespective of
      retreatment criteria, provided superior BCVA gains versus vPDT up to month 3.
      Ranibizumab treatment guided by disease activity criteria was noninferior to VA
      stabilization criteria up to month 6. Over 12 months, individualized ranibizumab
      treatment was effective in improving and sustaining BCVA and was generally well
      tolerated in patients with myopic CNV.

PMID- 24326107
TI  - Antibiotic choice for the prophylaxis of post-cataract extraction
      endophthalmitis.
AB  - OBJECTIVE: To determine the 8-year incidence of endophthalmitis after cataract
      surgery and to determine which surgical practices were associated with higher
      rates of endophthalmitis. DESIGN: Case-control study. PARTICIPANTS: A total of 75
      318 eyes undergoing cataract extractions, performed by 26 different surgeons at 4
      public hospitals and 5 nonhospital surgical facilities. METHODS: Cases of
      endophthalmitis were acquired using a detailed, prospectively designed
      demographic database. Controls were tabulated using volume data available from
      the provincial health care system. MAIN OUTCOME MEASURES: The primary outcome was
      the development of endophthalmitis. RESULTS: A total of 23 cases (13 with culture
      positive results) of postoperative endophthalmitis occurred, yielding an overall
      8-year incidence of 0.03%. The incidence of endophthalmitis varied between
      surgeons from 0% to 0.20%. Two surgeons had higher rates than the rest of the
      group: 1 high-volume surgeon (1059.4+/-231.9 mean cases per year) with an
      incidence of 0.08% (n = 7; P = 0.004) and 1 low-volume surgeon (123.5+/-44.8 mean
      cases per year) with an incidence of 0.20% (n = 2; P = 0.002). On univariate
      analysis, the rate of endophthalmitis was not influenced by the use of
      intracameral (0.898) or subconjunctival antibiotics (0.331), whereas the use of
      moxifloxacin was associated with a lower rate of endophthalmitis (P = 0.029).
      Surgery at 1 private facility (P = 0.046) and the use of timolol at the end of
      the procedure (P = 0.007) were associated with a higher rate of endophthalmitis.
      Multivariate analysis demonstrated that the odds of endophthalmitis was lower if
      a second-generation (P = 0.02) or fourth-generation (P = 0.008) fluoroquinolone
      antibiotic was used after surgery. In contrast, the odds of endophthalmitis
      occurring was higher if timolol (P = 0.0002) was used at the end of the procedure
      or if the surgery was performed at one of the private facilities (P = 0.009).
      CONCLUSIONS: The rate of endophthalmitis was lower if a fluoroquinolone was used
      after surgery. In contrast, endophthalmitis was more likely to occur if timolol
      was used at the end of the procedure or if surgery was performed at one of the
      private facilities.

PMID- 24326108
TI  - [A man with spontaneous pain in shoulders and hips].
AB  - A 19-year-old man presented with spontaneous pain in both hips and shoulders. X
      ray of the pelvis showed osteopenia throughout the pelvis and a late stadium of
      coxarthrosis. MRI showed osteonecrosis on both sides in the femur head and
      acetabulum as well as both humerus heads. Glucocorticoids may induce
      osteonecrosis. 

PMID- 24326109
TI  - [A woman with red-purple blotches].
AB  - A 56-year-old woman presented with red-purple blotches on both forearms which had
      suddenly appeared without any pain, pruritus or trauma. Laboratory investigation
      showed no abnormalities. Histopathology revealed non-inflammatory actinic
      purpura. These purpura are frequently seen in older people due to a weakened
      collagen framework. 

PMID- 24326110
TI  - [A man with a rapidly growing tumor of the hand].
AB  - A 28-year-old man suffered a minor trauma from his fifth finger of the left hand.
      The small wound developed rapidly within weeks. A granoloma pyogenicum was
      diagnosed. This is a benign vascular tumor mostly resulting after minor trauma.
      Treatment is surgical removal of the lesion. 

PMID- 24326111
TI  - [A man with an oppressive sensation behind the orbit].
AB  - A 68-year-old man presented with an intraconal lesion on the right side, which
      increased in size after a CT-scan in prone position. This phenomenon is
      diagnostic for an orbital varix. 

PMID- 24326112
TI  - [Multidisciplinary guideline irritable bowel syndrome].
AB  - The multidisciplinary guideline 'Diagnostics and treatment of irritable bowel
      syndrome (IBS)' provides the basis for a properly coordinated collaboration
      between the patient suffering from IBS and all healthcare providers involved in
      his or her treatment, such as the general practitioner, gastroenterologist,
      internist, occupational-health physician, dietitian and psychologist. The
      diagnosis 'IBS' is often made in accordance with diagnostic criteria, such as the
      Rome III criteria, but a somatic condition needs to be excluded first. If there
      are no indications for this, additional diagnostic tests are not necessary.
      Management of the condition consists primarily of advice on life-style plus non
      pharmacological interventions, in addition to explaining the condition and
      providing information. Drug treatment is rarely indicated. If the IBS symptoms
      have a significant impact on quality of life and patients do not respond to the
      measures taken in accordance with this general policy, there are three options
      for psychotherapeutic treatment. When the symptoms result in absenteeism or other
      work-related problems, the doctor can advise the patient to contact the
      occupational-health physician and to search for specific solutions in
      consultation with the employer. When individual advice is required or if the
      patient's diet is not well-balanced, a referral to the dietitian will follow.

PMID- 24326113
TI  - [Bariatric surgery: part of a systematic approach to obesity].
AB  - Bariatric surgery is becoming popular as treatment of morbid obesity. With this
      popularity there is a danger that it surpasses or even replaces conservative
      medical therapy. Instead, bariatric surgery should be part of a systematic
      approach in the treatment of obesity. There is a new Dutch practice guideline on
      the treatment of morbid obesity in which conservative treatment is hardly
      covered. There is little evidence of the highest level to support the
      recommendations in this guideline. 

PMID- 24326114
TI  - [Inflammation and structural organ damage: chicken or egg?].
AB  - It is not inflammation but functional and/or anatomical loss of integrity of
      target organs that is the major determinant of morbidity in many immune-mediated
      inflammatory diseases (IMIDs). This structural and often irreversible tissue
      damage is generally considered to be a direct or indirect consequence of
      inflammation (through failed repair mechanisms). However, recent clinical
      observations in rheumatic diseases, demonstrate clearly that the postulated
      causal relationship between inflammation and structural damage does certainly not
      hold true in all IMIDs. On the contrary, potent anti-inflammatory treatments
      suggest an uncoupling of inflammation and damage in diseases such as ankylosing
      spondylitis. The author proposes a third and intriguing alternative hypothesis:
      inflammation and stromal remodelling are causally linked but it is the latter
      that drives the former. If this hypothesis is correct, we should focus our
      therapeutic efforts on pathways of tissue remodelling rather than on inflammation
      in IMIDs such as ankylosing spondylitis, but potentially also scleroderma or
      asthma. 

PMID- 24326116
TI  - [Medical nutrition in Alzheimer's: the trials].
AB  - We describe the small but statistically significant effects of the medical
      nutrition diet 'Souvenaid' on memory in early Alzheimer's disease in two
      published randomised clinical trials. We specifically discuss the design and
      statistical approach, which were predefined and meet current standards in the
      field. Further research is needed to substantiate the long term effects and learn
      more about the mode of action of Souvenaid. 

PMID- 24326117
TI  - Zoonotic infection with Chlamydia psittaci at an avian refuge centre.
AB  - This paper reports the zoonotic transmission of Chlamydia psittaci at a wild bird
      refuge centre resulting in the infection of members of the staff. Pharyngeal
      swabs were culture positive in 26% (11/42) of the sampled birds, and molecular
      characterisation of isolates revealed genotypes A, B, D, and E/B. The finding
      reflects multiple distinct infections and highlights the endemic nature of this
      pathogen in avian wildlife. Two clinically normal birds being prepared for
      release were found to be excreting C. psittaci genotype B or E/B and viable
      genotype B was detected in pharyngeal swabs from 30% (3/10) of the human workers
      tested. The findings suggest there should be enhanced surveillance and control
      measures in place in bird rehabilitation centres in order to minimise the risk of
      both zoonoses and of re-introduction of infection back into wildlife populations.

PMID- 24326119
TI  - Epigenetic regulation of the Plasmodium falciparum genome.
AB  - Recent research has highlighted some unique aspects of chromatin biology in the
      malaria parasite Plasmodium falciparum. During its erythrocytic lifecycle P.
      falciparum maintains its genome primarily as unstructured euchromatin. Indeed
      there is no clear role for chromatin-mediated silencing of the majority of the
      developmentally expressed genes in P. falciparum. However discontinuous stretches
      of heterochromatin are critical for variegated expression of contingency genes
      that mediate key pathogenic processes in malaria. These range from invasion of
      erythrocytes and antigenic variation to solute transport and growth adaptation in
      response to environmental changes. Despite lack of structure within euchromatin
      the nucleus maintains functional compartments that regulate expression of many
      genes at the nuclear periphery, particularly genes with clonally variant
      expression. The typical components of the chromatin regulatory machinery are
      present in P. falciparum; however, some of these appear to have evolved novel
      species-specific functions, e.g. the dynamic regulation of histone variants at
      virulence gene promoters. The parasite also appears to have repeatedly acquired
      chromatin regulatory proteins through lateral transfer from endosymbionts and
      from the host. P. falciparum chromatin regulators have been successfully targeted
      with multiple drugs in laboratory studies; hopefully their functional divergence
      from human counterparts will allow the development of parasite-specific
      inhibitors. 

PMID- 24326118
TI  - C. elegans epigenetic regulation in development and aging.
AB  - The precise developmental map of the Caenorhabditis elegans cell lineage, as well
      as a complete genome sequence and feasibility of genetic manipulation make this
      nematode species highly attractive to study the role of epigenetics during
      development. Genetic dissection of phenotypical traits, such as formation of egg
      laying organs or starvation-resistant dauer larvae, has illustrated how chromatin
      modifiers may regulate specific cell-fate decisions and behavioral programs.
      Moreover, the transparent body of C. elegans facilitates non-invasive microscopy
      to study tissue-specific accumulation of heterochromatin at the nuclear
      periphery. We also review here recent findings on how small RNA molecules
      contribute to epigenetic control of gene expression that can be propagated for
      several generations and eventually determine longevity. 

PMID- 24326121
TI  - Cadmium mobility in sediments and soils from a coal mining area on Tibagi River
      watershed: environmental risk assessment.
AB  - The risk of cadmium contamination in the Tibagi River watershed (Parana State,
      Brazil) affected by past coal mining activities was assessed through sorption
      desorption modeling for sediment and soil samples. The acidic character of the
      samples resulted in more competition between the cadmium ions and protons,
      thereby influencing the cadmium sorption-desorption. The sorption isotherms were
      fitted to the Langmuir and Freundlich single models and to the dual-site Langmuir
      Freundlich (or Sips) model. The single-site models indicated a low-energy
      character of sorption sites on the sample sorption sites, whereas the dual-site
      model explained the availability of higher-affinity and lower-affinity non
      specific sites. The correlation of the sorption and desorption constants with the
      physicochemical and mineralogical characteristics of the samples showed that the
      cadmium sorption behavior was significantly affected by the pH, point of zero
      charge, and also by the magnesium, aluminum, calcium and manganese amounts.
      Besides, the desorption rate and hysteresis index suggested a high risk of
      cadmium mobilization along the Tibagi River basin. 

PMID- 24326120
TI  - Changes in the oral environment after placement of lingual and labial orthodontic
      appliances.
AB  - BACKGROUND: This study compared the oral hygiene and caries risk of patients
      treated with labial and lingual orthodontic appliances throughout a prospective
      evaluation of the status of the oral environment before and after bracket
      placement. METHODS: A total of 20 orthodontic patients aged 19 to 23 years were
      included in the study and were divided into two groups: 10 patients wore Roth
      labial appliance (American Orthodontics, Sheboygan, WI, USA) and 10 patients wore
      STb lingual appliance (Ormco Corporation, Glendora, CA, USA). Plaque index (PI),
      gingival bleeding index (GBI), salivary flow rate, saliva buffer capacity,
      salivary pH, and Streptococcus mutans and Lactobacillus counts in saliva were
      determined at three time points: before orthodontic appliance placement (T0), 4
      weeks after bonding (T1), and 8 weeks after bonding (T2). After appliance
      placement, all patients were periodically educated to the oral hygiene
      procedures. Wilcoxon rank and Mann-Whitney U tests were used to determine
      intragroup and intergroup differences as regards qualitative data. To compare
      quantitative data between the groups, chi-square and Fisher's exact tests were
      undertaken, while intragroup differences were tested with McNemar test. The level
      of statistical significance was set at p<0.05. RESULTS: Statistical analysis of
      the data obtained revealed a statistically significant difference between the
      data of T0 and T1 and the data of T0 and T2 of the PI scores and between T0 and
      T2 of the GBI scores in the group treated with the lingual appliance. The GBI
      value increased significantly between T0 and T1 but decreased significantly
      between T1 and T2 (p<0.01) in the group treated with labial appliance. S. mutans
      counts increased significantly between T0 and T2 in the saliva samples of
      patients treated with lingual appliance. No statistically significant differences
      were found between S. mutans and Lactobacillus counts at the three terms of
      saliva collection in patients treated with labial appliance. No statistically
      significant differences were found between the two groups at the three time
      points as regards the salivary flow rate and saliva buffer capacity. CONCLUSIONS:
      Lingual and labial orthodontic appliances showed a different potential in
      modifying the investigated clinical parameters: patients wearing STb lingual
      orthodontic appliance had more plaque retention 4 and 8 weeks after bonding,
      while there were more gingival inflammation and more S. mutans counts 8 weeks
      after bonding. No differences were found between the two groups as regards the
      Lactobacillus counts, the salivary flow rate, and saliva buffer capacity.

PMID- 24326122
TI  - The obesity paradox and acute kidney injury: beneficial effects of hyper
      inflammation?
AB  - In the general population, obesity is associated with an increased mortality
      risk, whereas several epidemiological studies demonstrated a protective effect of
      obesity in critically ill patients. In this context, Sleeman and colleagues
      investigated the effects of obesity on kidney function in a well-established
      porcine model of cardiopulmonary bypass. The authors confirm literature data that
      obesity per se is associated with a chronic hyper-inflammatory status.
      Nevertheless, obese swine undergoing the surgical procedure presented with
      attenuated kidney dysfunction and tissue apoptosis. The authors suggest that the
      chronic inflammation causes pre-conditioning against excessive acute hyper
      inflammation. The authors have to be commended for using a long-term, clinically
      relevant model that, moreover, addresses a variety of putative mechanisms. The
      study is discussed in the context of the controversial findings that, in contrast
      to the existing literature on improved survival, most studies available suggest a
      higher incidence and severity of acute kidney injury in obese patients when
      compared with lean controls. 

PMID- 24326123
TI  - Whole-blood gene expression profiling in ankylosing spondylitis identifies novel
      candidate genes that may contribute to the inflammatory and tissue-destructive
      disease aspects.
AB  - We performed a comprehensive gene expression analysis to identify differentially
      expressed genes (DEGs) between AS (ankylosing spondylitis) and health controls. A
      total of 1454 DEGs were obtained, including 919 up-regulated genes and 535 down
      regulated genes. There were 218 interactions and 224 pairs in the conPPI network.
      Topological analysis showed that 11 genes had a close relationship with AS. GO
      (gene ontology) functional enrichment analysis of the two modules showed that the
      DEGs in conPPI mainly participated in the biologic process of immune response.
      The KEGG pathway analysis showed that most DEGs in the two modules were enriched
      into cell receptor signaling pathway, natural killer cell mediated cytotoxicity
      and primary immunodeficiency. We hypothesized that these DEGs associated with
      immune response DEGs might provide basic for depth understanding of the AS
      development. 

PMID- 24326125
TI  - Comparison of estimated glomerular filtration rates using creatinine values
      generated by iSTAT and Cobas 6000.

PMID- 24326124
TI  - Macromolecular prodrug of dexamethasone prevents particle-induced peri-implant
      osteolysis with reduced systemic side effects.
AB  - Aseptic implant loosening related to implant wear particle-induced inflammation
      is the most common cause of failure after joint replacement. Modulation of the
      inflammatory reaction to the wear products represents a rational approach for
      preventing aseptic implant failure. Long-term treatment using anti-inflammatory
      agents, however, can be associated with significant systemic side effects due to
      the drugs' lack of tissue specificity. To address this issue, N-(2-hydroxypropyl)
      methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) was developed and
      evaluated for prevention of wear particle-induced osteolysis and the loss of
      fixation in a murine prosthesis failure model. Daily administration of free
      dexamethasone (Dex) was able to prevent wear particle-induced osteolysis, as
      assessed by micro-CT and histological analysis. Remarkably, monthly P-Dex
      administration (dose equivalent to free Dex treatment) was equally effective as
      free dexamethasone, but was not associated with systemic bone loss (a major
      adverse side effect of glucocorticoids). The reduced systemic toxicity of P-Dex
      is related to preferential targeting of the sites of wear particle-induced
      inflammation and its subcellular sequestration and retention by local
      inflammatory cell populations, resulting in sustained therapeutic action. These
      results demonstrate the feasibility of utilizing a macromolecular prodrug with
      reduced systemic toxicity to prevent wear particle-induced osteolysis. 

PMID- 24326126
TI  - Minimal interference from paricalcitol (Zemplar(r)) in underivatized 1,25
      dihydroxyvitamin D LC-MS/MS assays.

PMID- 24326128
TI  - Change in urinary N-acetyl-beta-d-glucosaminidase levels relevant to postprandial
      glycemic control conditions in subjects without diabetes mellitus.
AB  - BACKGROUND: To assess the relationship between the serum level of 1,5
      anhydroglucitol (1,5-AG), a marker of postprandial hyperglycemia, and the ratio
      of the urinary activity of N-acetyl-beta-d-glucosaminidase to creatinine (NAG
      index) in subjects without diabetes mellitus (DM). METHODS: This was a cross
      sectional study with 495 subjects without DM who had an estimated glomerular
      filtration rate>=30ml/min/1.73m(2). Subjects were divided into tertiles based on
      serum 1,5-AG levels: high (>21.0MUg/ml), middle (14.0-21.0MUg/ml), and low
      (<14.0MUg/ml). Adjusted odds ratios for an elevated urinary NAG index (>5.8U/g
      creatinine) according to the HbA1c (<=5.4%, 5.5%-5.9%, and 6.0%-6.4%) and 1,5-AG
      tertiles were calculated. RESULTS: The NAG index was negatively correlated with
      the serum 1,5-AG level in all subjects. The slopes of the regression lines for
      these variables did not differ significantly between elderly (>=65y) and
      nonelderly subjects. As compared with high 1,5-AG and HbA1c<=5.4%, the odds
      ratios for an elevated urinary NAG index increased progressively to 7.71 across
      the categories of low 1,5-AG and HbA1c of 6.0% to 6.4%. CONCLUSION: Poor control
      of postprandial glucose is related to an elevated urinary NAG index in persons
      without DM.

PMID- 24326127
TI  - Identification of a novel NOG mutation in a Chinese family with proximal
      symphalangism.
AB  - Proximal symphalangism (SYM1) is an autosomal dominant disorder, mainly
      characterized by variable fusion of the proximal interphalangeal joints of the
      hands and feet. To date, two genes, GDF5 and NOG, have been reported to associate
      with SYM1. Herein, we clinically characterized a Chinese family with fusions of
      the bilateral proximal interphalangeal joints in the 2-5 digits without
      conductive hearing loss. Direct DNA sequencing of the two genes revealed a novel
      heterozygous missense mutation (c.499C>T, p.R167C) in the NOG gene. This mutation
      co-segregates with the phenotype in the family and is not present in the 200
      control individuals. The c.499C>T mutation is predicted to change the conserved
      amino acid arginine at codon 167 to cysteine at the protein level. A different
      mutation in the same codon (R167G) has been described to cause brachydactyly type
      B2 (BDB2). Our work indicates that the c.499C>T (R167C) mutation is likely to
      represent the pathogenic mutation in the family. This finding broadens the
      spectrum of NOG mutations associated with SYM1 and will help to provide genetic
      counseling to the affected family. 

PMID- 24326129
TI  - How to achieve harmonisation of laboratory testing -The complete picture.
AB  - Harmonisation is likely to be an important contributor to ensure high quality
      laboratory testing, thus potentially improving patient outcome. Efforts for
      harmonisation must be made in the total testing process, from test requesting to
      communication of the laboratory test results and its consequences to the patient.
      In this article, suggestions are given about what level of harmonisation is
      possible at the various steps of the testing process, who could be responsible
      for facilitating and monitoring the effects of harmonisation, and what are likely
      barriers to achieving harmonisation. Harmonisation can be achieved at local,
      national and international levels, and will be most challenging when it involves
      more than one profession as in the extra-analytical phases. Key facilitators will
      be laboratory associations, regulatory bodies and accreditation systems, whereas
      barriers are likely to be reimbursement systems or economic factors, opinion
      leaders and manufacturers. A challenge is to try to turn barriers into
      facilitators. Harmonisation effects can in most settings be monitored by external
      quality assurance organisations provided that schemes are expanded to cover all
      relevant steps and phases. We must combine our efforts, both within our
      profession as well as in cooperation with others, to achieve harmonisation of the
      total testing process, in the best interests of the patient.

PMID- 24326131
TI  - Determination of 23 phthalic acid esters in food by liquid chromatography tandem
      mass spectrometry.
AB  - A rapid and sensitive method was developed for the determination of 23 phthalates
      in food samples including milk-based products, distilled liquor, wine, beverage,
      grain, meat, oil, biscuit (cookie), and canned food by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). Liquid samples were exacted by acetonitrile,
      while solid samples were prepared by QuEChERS or glass-based SPE methods. The 23
      phthalates were separated on Poroshell 120 EC-C18 column and followed by positive
      electrospray ionization as well as multi-reaction monitoring provided by a triple
      quadrupole tandem mass spectrometer. To reduce contamination, the plastic
      materials were avoided in sample handling and preparation . The LODs were between
      0.8 and 15 MUg kg(-1) and LOQs were between 10 and 100 MUg kg(-1). By using
      different concentrations: 100, 500, and 1000 MUg kg(-1)) for DINP and DIDP; 50,
      100, and 1000 MUg kg(-1) for other 21 phthalate compounds, the spiked recoveries
      were within 75.5-115.2% and the relative standard deviations (RSDs) were in the
      range of 3.2-18.9%. The proposed protocol was then applied to the analysis of 623
      real samples collected from the two sides of the Taiwan Straits, and the DEHP was
      found in almost all samples tested in this study, with levels ranging from 0.02
      to 2685 mg kg(-1). The present study demonstrated a rapid, sensitive, and
      accurate method for determining 23 phthalates in foodstuffs.

PMID- 24326130
TI  - Targeting MET kinase with the small-molecule inhibitor amuvatinib induces
      cytotoxicity in primary myeloma cells and cell lines.
AB  - BACKGROUND: MET is a receptor tyrosine kinase that is activated by the ligand HGF
      and this pathway promotes cell survival, migration, and motility. In accordance
      with its oncogenic role, MET is constitutively active, mutated, or over-expressed
      in many cancers. Corollary to its impact, inhibition of MET kinase activity
      causes reduction of the downstream signaling and demise of cells. In myeloma, a B
      cell plasma malignancy, MET is neither mutated nor over-expressed, however, HGF
      is increased in plasma or serum obtained from myeloma patients and this was
      associated with poor prognosis. The small-molecule, amuvatinib, inhibits MET
      receptor tyrosine kinase. Based on this background, we hypothesized that
      targeting the HGF/MET signaling pathway is a rational approach to myeloma therapy
      and that myeloma cells would be sensitive to amuvatinib. METHODS: Expression of
      MET and HGF mRNAs in normal versus malignant plasma cells was compared during
      disease progression. Cell death and growth as well as MET signaling pathway were
      assessed in amuvatinib treated primary myeloma cells and cell lines. RESULTS:
      There was a progressive increase in the transcript levels of HGF (but not MET)
      from normal plasma cells to refractory malignant plasma cells. Amuvatinib readily
      inhibited MET phosphorylation in primary CD138+ cells from myeloma patients and
      in concordance, increased cell death. A 48-hr amuvatinib treatment in high HGF
      expressing myeloma cell line, U266, resulted in growth inhibition. Levels of
      cytotoxicity were time-dependent; at 24, 48, and 72 h, amuvatinib (25 MUM)
      resulted in 28%, 40%, and 55% cell death. Consistent with these data, there was
      an amuvatinib-mediated decrease in MET phosphorylation in the cell line.
      Amuvatinib at concentrations of 5, 10, or 25 MUM readily inhibited HGF-dependent
      MET, AKT, ERK and GSK-3-beta phosphorylation. MET-mediated effects were not
      observed in myeloma cell line that has low MET and/or HGF expression.
      CONCLUSIONS: These data suggest that at the cellular level MET/HGF pathway
      inclines with myeloma disease progression. Amuvatinib, a small molecule MET
      kinase inhibitor, is effective in inducing growth inhibition and cell death in
      myeloma cell lines as well as primary malignant plasma cells. These cytostatic
      and cytotoxic effects were associated with an impact on MET/HGF pathway.

PMID- 24326132
TI  - An artificial receptor fabricated by target recognition determinant imprinting
      for selective capture of alpha-amanitin.
AB  - This is the first reported work of artificial alpha-amanitin receptors which are
      prepared using the design and synthesis of a template molecule based on an alpha
      amanitin recognition determinant imprinting strategy. The resultant molecularly
      imprinted polymers (MIPs) are evaluated using high performance liquid
      chromatography (HPLC), binding experiment, nitrogen adsorption measurement, and
      solid-phase extraction. Experiment clearly demonstrates that the MIPs as the HPLC
      stationary phase can specifically recognize alpha-amanitin from analogues. The
      MIPs also successfully adsorb trace amounts of alpha-amanitin in spiked serum
      samples selectively pretreated and enriched through molecularly imprinted solid
      phase extraction. The limit of detection and recovery is 3.0 ng mL(-1) and 88.5
      95.9%, respectively, for alpha-amanitin in serum samples. The high specific
      adsorption and excellent selectivity of the MIPs arises from imprinting effects
      related to the imprinting cavity of the polymeric matrix, the metal-coordination
      bond, and the hydrogen bond between the receptor and ligand.

PMID- 24326133
TI  - Voltage-step pulsed electromembrane as a novel view of electrical field-induced
      liquid-phase microextraction.
AB  - In the present work, the effect of application of voltage steps on extraction
      efficiency of pulsed electromembrane extraction (PEME) was investigated for the
      first time. The effects of voltage variations including initial and final
      voltages, number of steps between the initial and final voltages as well as their
      time durations were studied on the extraction efficiencies of three different
      classes of analytes. These classes include amitriptyline (AMI) and nortriptyline
      (NOR) as more hydrophobic analytes, diclofenac (DIC) and mefenamic acid (MEF) as
      acidic drugs and salbutamol (SB) and terbutaline (TB) as hydrophilic compounds.
      It was anticipated that the application of high voltages is not necessary at the
      beginning of the extraction, since large amounts of target analytes exist around
      the supported liquid membrane (SLM)/sample solution interface. So, they could be
      easily transferred into the acceptor phase utilizing lower voltages. Results
      showed that the benefits of voltage-step PEME (VS-PEME) are more obvious in
      systems with low electrical resistance (regarding the SLM composition).
      Efficiencies of VS-PEME for extraction of AMI and NOR (96% and 89% for AMI and
      NOR, respectively) were comparable with those achieved from applying a constant
      voltage (95% for AMI and 83% for NOR). However, recoveries from the VS-PEME of
      DIC and MEF (53% and 44% for DIC and MEF, respectively) were significantly higher
      than those from the application of a constant voltage (33% for DIC and 31% for
      MEF). Also, recoveries obtained from the VS-PEME for SB and TB were approximately
      3 orders of magnitude greater than those from a constant voltage. Moreover, it
      was demonstrated that in all cases analytes could effectively be extracted at the
      beginning of extraction by applying low voltages. 

PMID- 24326134
TI  - A study on the properties and reactivity of naphthoquinone-cobalt(III) prototypes
      for bioreductive prodrugs.
AB  - Our group has recently initiated a study on the development of new prototypes for
      bioreductive prodrugs, based on Co(III) complexes with the ligand 2,2'-bis(3
      hydroxy-1,4-naphthoquinone), H2bhnq. The focus of this work is to investigate the
      dissociation of bhnq(-2) from the complex upon reduction, and the effects of pH,
      redox potential, oxygen concentration and nature of the auxiliary ligands on this
      reaction. The bhnq(2-) ligand is a "non-cytotoxic" agent that was chosen as a
      probe for the reactivity studies due to its suitable chromophoric properties, at
      the same time that it resembles more cytotoxic naphthoquinones relevant for
      cancer therapy. In this way, two Co(III) complexes [Co(bhnq)(L1)]BF4.H2O (1) and
      [Co(bhnq)(L2)]BF4.H2O (2) (L1=N,N'-bis(pyridin-2-ylmethyl)ethylenediamine and
      L2=N,N'-dimethyl-N,N'-bis(pyridin-2-ylmethyl)ethylenediamine) were synthesized
      and fully characterized. The gallium analogs [Ga(bhnq)(L1)]NO3.3H2O (3) and
      [Ga(bhnq)(L2)]NO3.3H2O (4) were also prepared for helping with the assignments of
      the redox properties of the cobalt complexes and the structure of 2. Cyclic
      voltammetry analysis revealed a pH-independent quasi-reversible Co(III)/Co(II)
      process at -0.22 and -0.08V vs NHE for 1 and 2, respectively. An O2-dependent
      dissociation of bhnq(2-) was observed for the reaction of 1 with ascorbic acid.
      For 2, the dissociation of bhnq(2-) was found to be independent on the
      concentration of O2 and faster than in 1, with little influence of the pH on both
      complexes. The difference in reactivity between 1 and 2 and their redox
      properties, among other factors, suggests that 1 undergoes redox cycling, pointed
      out as a key feature for a prodrug to achieve hypoxic selectivity. 

PMID- 24326136
TI  - [Hyperglycaemic crises in children and adolescents].
AB  - Recently the Paediatric Association of the Netherlands (NVK) published a new
      guideline on the treatment of diabetic ketoacidosis (DKA) and hyperglycaemic
      hyperosmolar syndrome (HHS) in children and adolescents. DKA comprises
      hyperglycaemia, ketosis and acidosis. Cerebral oedema is a feared, life
      threatening complication of DKA. HHS is characterized by hyperglycaemia,
      hyperosmolarity, severe dehydration, and little or no ketone production. Multi
      organ failure, rhabdomyolysis and thrombosis are the most common complications.
      The NVK guideline distinguishes between treatment of DKA and treatment of HHS, in
      contrast with the draft version of the Netherlands Association of Internal
      Medicine guideline on diabetes. To prevent cerebral oedema in children with DKA,
      it is necessary that both rehydration and metabolic correction are done slowly
      and carefully. Use of hypotonic fluids is not recommended. Correction of
      hyperglycaemia is of secondary importance and insulin should be started at a low
      dosage. Correction of intravascular hypovolaemia is the most important treatment
      in children with HHS. If adequate fluid replacement does not cause serum glucose
      levels to drop sufficiently, then administration of insulin should be considered.
      Fluid replacement is the initial treatment of HHS. Insulin administration should
      be considered when serum glucose concentrations are no longer declining
      adequately with fluid administration alone.

PMID- 24326135
TI  - Hypermethylation of EDNRB promoter contributes to the risk of colorectal cancer.
AB  - OBJECTIVE: Colorectal cancer (CRC) is one of the most common digestive
      malignancies in the world. EDNRB is a new candidate tumor suppressor gene which
      is often down-regulated or even silenced by promoter hypermethylation in various
      human cancers. However, the function of EDNRB gene in CRC remains unknown. In
      this study, we examined the expression and DNA methylation of EDNRB in CRC
      tissues. METHODS: A total of 42 paired CRC and adjacent normal tissue samples
      were used to determine mRNA levels and DNA methylation status of EDNRB gene by
      qRT-PCR and methylation-specific PCR (MSP), respectively. RESULTS: Our study
      showed that EDNRB promoter hypermethylation was more frequently in CRC tissues
      than in the normal tissues (92.86 versus 59.52, p = 0.001). Consequently,
      significantly lower level of EDNRB mRNA was found in CRC tumor samples than in
      normal samples (0.31 +/- 0.91 versus 0.70 +/- 1.18, p = 0.032). CONCLUSIONS: Our
      results suggested that EDNRB promoter hypermethylation might downregulate its
      gene expression in CRC, and thus played an important role in the development of
      CRC. THE VIRTUAL SLIDE: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7420980471113303.

PMID- 24326137
TI  - [Bypass surgery or angioplasty: which treatment for which patient?].
AB  - In patients with symptoms of ischaemic heart disease, despite optimal medical
      therapy, a PCI or CABG may be indicated if the coronary arteries are narrowed.
      Decisions regarding PCI or CABG need to be taken by the local heart team,
      consisting of a cardiothoracic surgeon and an interventional cardiologist. After
      a complete diagnostic work-up, the referring cardiologist presents the patient
      with accompanying written information supporting revascularisation. The decision
      of the heart team takes the characteristics of each individual patient into
      account and, most importantly, the coronary angiogram. Despite improvements in
      medical and interventional treatments, mortality and morbidity remain high among
      patients with NSTEMI. Early risk stratification is essential to determine those
      patients who can be treated safely with medical therapy and those who require
      interventional treatment. Ad hoc PCI is indicated in patients with STEMI or
      haemodynamic instability.

PMID- 24326138
TI  - [Multidisciplinary practice guideline 'Marfan syndrome'].
AB  - Marfan syndrome is a multi-system disorder of dominant inheritance in which the
      cardiovasculature, in particular the aorta, the eyes and the skeleton are
      affected. Diagnostic assessment and treatment of patients who are suspected of or
      have Marfan syndrome should preferably be done by multidisciplinary teams such as
      those found in specialised Marfan syndrome centres. The practice guideline is
      intended for all care givers involved with the recognition, diagnosis,
      consultations and the medicinal and surgical treatment of Marfan patients; it
      includes referral criteria and information on the referral process. A diagnosis
      of Marfan syndrome is based on international criteria in which aortic root
      dilatation and dissection, ectopia lentis, an affected first-degree family member
      and a pathogenic FBN1 mutation are the cardinal features. Alternative diagnoses
      are also included in the practice guideline. Recommendations are given for the
      monitoring and treatment of Marfan patients during pregnancy and delivery. Advice
      on lifestyle is mainly focussed on sports activities.

PMID- 24326139
TI  - [A strong man with a weak shoulder].
AB  - A 47-year-old former olympic athlete had pain and weakness of his left shoulder.
      There was no prior trauma. He had full range-of-motion and a scapular dyskinesia.
      There was atrophy of the trapezius and sternocleidomastoideus muscles. He was
      diagnosed with 'idiopathic neuritis of the accessorius nerve'.

PMID- 24326140
TI  - [Long-term effects of childhood cancer in primary care].
AB  - Recent publications on the long-term effects of treatment for childhood cancer
      underline the need for a larger role of primary care in the guidance given to
      these patients regarding risks and lifestyle. This group is growing and there are
      a large number of potential long-term risks. Practice guidelines on registration
      in the electronic patient file are needed. Sometimes active screening is
      required, sometimes potential risk factors become manifest. The replacement of
      secondary care (often specialised outpatient clinics) with primary care should be
      an active process, which is supported by personalised and up-to-date information
      in the form of a letter from the specialist to the primary care physician.
      Patients can play an important role in drawing up the primary care follow-up
      plan. 

PMID- 24326141
TI  - [The core of solidarity].
AB  - Dutch Journal of Medicine (NTVG) Lecture 2013: Organized solidarity in a welfare
      state is impersonal, restricted and based on enlightened self-interest. Critics
      of the welfare state argue that it is obsolete and we should aim for a society
      based on individual participation. They believe that people now prefer
      individualized care, that it is no longer possible to set boundaries and that too
      much altruism is required from those with higher incomes. In this year's NTvG
      lecture Margo Trappenburg contended that this criticism is unjust. Many people
      prefer professional care to care from the family or from volunteers and it could
      be possible to set boundaries again: recent developments within the medical
      profession are hopeful. And although the more highly educated make a greater
      financial contribution to the welfare state, those with a lower level of
      education show more, and more frequent, active solidarity. There is insufficient
      reason to abolish the welfare state and replace it with a society of greater
      individual participation.

PMID- 24326142
TI  - Prevalence of malocclusions, oral habits and orthodontic treatment need in a 7-
      to 15-year-old schoolchildren population in Tirana.
AB  - BACKGROUND: The aim of present study was to determine the prevalence of
      malocclusions, oral habits and the need for orthodontic treatment in a sample of
      7- to 15-year-old Albanese schoolchildren. METHODS: The final sample comprised
      2,617 subjects (1,257 males and 1,360 females), all orthodontically untreated.
      Occlusal relationship and the functional analysis were recorded for all subjects.
      The prevalence rates for the dental health component of the index of orthodontic
      treatment need (IOTN) were calculated. Comparisons between genders were performed
      for the prevalence of malocclusions, oral habits and IOTN grades (chi-square
      tests). RESULTS: Class I, class II and class III malocclusions and asymmetries
      were observed in 40.4%, 29.2%, 3.2% and 27.1% of the sample, respectively. There
      were 2,108 subjects (80.6%) that showed oral habits, with females (82.1%)
      presenting with a greater prevalence rate than males (78.9%). The objective need
      for orthodontic treatment (grades 4 and 5 of IOTN) was registered in 1,077
      subjects (41.2%). This prevalence rate is higher than those reported for other
      European countries. No significant differences between genders were found for the
      IOTN grades. CONCLUSIONS: The findings of the present study revealed the need to
      improve public health plans for orthodontic prevention and screening and to
      organise the resources in this area in Albania.

PMID- 24326143
TI  - Skeletal and dental characteristics in subjects with ankyloglossia.
AB  - BACKGROUND: The role of ankyloglossia in etiology of malocclusion is not much
      discussed over the years. The aim of the present study was to assess the skeletal
      and dental characteristics in subjects with ankyloglossia. METHODS: Fifty-seven
      subjects diagnosed with ankyloglossia (group 1) were compared with 60 subjects
      (group 2) without ankyloglossia, who had class I skeletal base. Ankyloglossia was
      diagnosed and graded (mild, moderate, severe and very severe) using Kortlow's
      method. SNA, SNB, ANB, Go-Gn-SN angle, FMA, maxillary and mandibular intercanine
      widths and intermolar widths, tooth size-arch length discrepancy in maxillary and
      mandibular arches and overbite were measured. Independent t test was used to
      compare the mean parameters between the two groups. Analysis of variance and
      Tukey honestly significant difference were used to compare mean parameters among
      various grades of ankyloglossia. RESULTS: Majority of group 1 subjects belonged
      to class I skeletal base followed by class II and class III skeletal bases.
      Moderate ankyloglossia was most common in group 1. The mean maxillary and
      mandibular intercanine widths and maxillary intermolar width were statistically
      significant in independent t test (P<0.01) and reduced in group 1. In ANOVA
      followed by Tukey HS, the Go-Gn-SN angle and overbite were statistically
      significant among different grades of ankyloglossia (P<0.05). CONCLUSIONS:
      Subjects with ankyloglossia had reduced maxillary and mandibular intercanine
      widths and reduced maxillary intermolar width. The mandibular plane angle and
      overbite were altered with severity of ankyloglossia.

PMID- 24326144
TI  - Small RNA analysis of Potato spindle tuber viroid infected Phelipanche ramosa.
AB  - Plants defend themselves against virus/viroid infection by induction of a
      mechanism of viral RNA degradation or translation inhibition. This is achieved by
      the production of small RNAs referred to as small interfering RNAs and microRNA,
      the key molecules in establishment of RNA directed silencing. Potato Spindle
      Tuber Viroid (PSTVd) was the first viroid species to be identified as naturally
      infecting potato, and it was found to infect many other crop species, wild and
      ornamental plants. Recently the experimental host range of PSTVd was extended
      with the root non-photosynthetic parasitic weed--Phelipanche ramosa (L) Pomel.
      Here we examined the small RNA population in P. ramosa infected with PSTVd and we
      observed the presence of PSTVd derived small RNAs. The hotspot regions for
      production of those PSTVd specific small RNAs were defined by their mapping on
      the viroid genome sequence. Further, we evaluated the expression levels of
      selected conserved microRNA families in the viroid infected P. ramosa. Upon
      infection, two members of miRNA395 family were significantly accumulated, while
      several members of miRNA390, miRNA396, miRNA319, miRNA166, miRNA167 and miRNA159
      were strongly down-regulated. All these findings imply the involvement of various
      small RNA classes in the P. ramosa response to PSTVd infection.

PMID- 24326146
TI  - Solution processable titanium dioxide precursor and nanoparticulated ink:
      application in Dye Sensitized Solar Cells.
AB  - Colloidal TiO2 anatase nanoparticles of 4-8 nm diameter capped with 3,6,9
      trioxadecanoic acid (TODA) were synthesized at low temperature using water and
      ethanol as the solvents. ATR-FTIR and (1)H NMR characterization showed the
      capping acid capability of stabilizing the TiO2 nanoparticles through labile
      hydrogen bonds. The presence of the capping ligand permitted the further
      preparation of homogeneous and stable colloidal dispersions of the TiO2 powder in
      aqueous media. Moreover, after solvent evaporation, the ligand could be easily
      eliminated by soft treatments, such as UV irradiation or low-temperature thermal
      annealing. These properties have been used in this work to fabricate mesoporous
      TiO2 electrodes, which can be applied as photoanodes in Dye Sensitized Solar
      Cells (DSSCs). For the preparation of the electrodes, the as-synthesized
      mesoporous TiO2 nanoparticles were mixed with commercial TiO2 (Degussa P25) and
      deposited on FTO substrates by using the doctor blade technique. A mixture of
      water and ethanol was used as the solvent. A soft thermal treatment at 140 
      degrees C for 2h eliminated the organic compound and produced a sintered
      mesoporous layer of 6 MUm thickness. The photovoltaic performance of the DSSCs
      applying these electrodes sensitized with the N3 dye resulted in 5.6% power
      conversion efficiency.

PMID- 24326147
TI  - Salt, fruit and vegetable consumption and blood pressure development: a
      longitudinal investigation in healthy children.
AB  - Low salt intake and high fruit and vegetable intake (FVI) have been shown to
      reduce blood pressure (BP) in adults. Longitudinal data on the independent effect
      of both FVI and salt intake on BP in healthy normotensive children are not
      available yet. In the present study, we aimed to characterise the concomitant
      influence of salt intake and FVI on BP development throughout childhood and
      adolescence. We examined 435 healthy subjects, for whom at least three repeated
      measurements of BP had been taken and who had provided 24 h urine samples and 3 d
      weighed dietary records between 4 and 18 years of age. BP was measured using a
      mercury sphygmomanometer (Mercuro 300, WelchAllyn) and salt intake was determined
      based on 24 h Na excretion. The intra-individual change in salt intake was almost
      significantly associated with the change in systolic BP (SBP, P= 0.06) and
      marginally (P= 0.09) with that in diastolic BP (DBP) in puberty, but not in pre
      puberty. A 1 g/d increase in salt intake was associated with a 0.2 mmHg increase
      in SBP. In pre-puberty, but not in puberty, differences in FVI between children
      predicted between-person variations in SBP and DBP (P= 0.03). Corresponding
      findings were obtained for 24 h K excretion (a urinary indicator for FVI). A 100
      g/d lower FVI was related to a 0.4 mmHg higher BP value. In conclusion, in
      healthy children and adolescents with BP in the low-normal range, both salt
      intake and FVI may already start to influence BP, although at a small magnitude.
      The potential importance of establishing healthy eating habits in childhood for
      later BP development emphasises the role of higher FVI and lower salt intake in
      the prevention of hypertension in the long run.

PMID- 24326148
TI  - Unhealthy food in relation to posttraumatic stress symptoms among adolescents.
AB  - The linkage between mood states and unhealthy food consumption has been under
      investigation in the recent years. This study aimed to evaluate the associations
      between posttraumatic stress (PTS) symptoms after lifetime traumatic experiences
      and daily unhealthy food consumption among adolescents, taking into account the
      possible effects of physical inactivity, smoking, and a sense of coherence. A
      self-administered questionnaire measured symptoms of PTS, lifetime traumatic
      experiences, food frequency scale, sense of coherence scale in a representative
      sample of eighth grade pupils of the Kaunas, Lithuania, secondary schools
      (N=1747; 49.3% girls and 50.7% boys). In the logistic regression models, all
      lifetime traumatic events were associated with PTS symptoms, as well as were
      unhealthy foods, (including light alcoholic drinks, spirits, soft and energy
      drinks, flavored milk, coffee, fast food, chips and salty snacks, frozen
      processed foods; excluding sweet snacks, biscuits and pastries) and sense of
      coherence weakened the strength of the associations. However, physical inactivity
      and smoking showed no mediating effect for the majority of unhealthy foods. In
      conclusion, we found that intervention and preventive programs on PTS symptoms
      may be beneficial while dealing with behavioral problems (unhealthy diet,
      smoking, alcohol, physical inactivity) among adolescents. 

PMID- 24326149
TI  - Effect of fixed orthodontic appliances on salivary properties.
AB  - BACKGROUND: So far, a few studies have tried to investigate the relationship
      between the placement of fixed orthodontic appliances and the change of
      nonmicrobial salivary properties, mostly with conflicting outcomes and short-term
      assessment (up to 6 months from bracket placement). The purpose of this study was
      to evaluate the salivary flow rate, pH and buffer capacity prior to the beginning
      of therapy and after 1 year from bracket placement using a simple and
      commercially available chairside saliva check kit. METHODS: The study population
      consisted of 20 healthy patients (mean age, 16.5+/-4 years) scheduled for fixed
      orthodontic treatment. Salivary samples were taken just before bracket bonding
      (T0; baseline assessment) and after 1 year of treatment (T1; half-treatment
      assessment) using the GC Saliva-Check Kit (GC Corp., Leuven, Belgium). RESULTS:
      No statistically significant difference was detected between T0 and T1 for the
      salivary parameters examined in the present study. CONCLUSIONS: Under the
      conditions of this study, the placement of fixed orthodontic appliances did not
      change the salivary pH, buffer capacity and flow rate after 1 year of treatment
      if compared with the baseline assessment.

PMID- 24326150
TI  - Cone-beam computed tomography evaluation of periodontal and bone support loss in
      extraction cases.
AB  - BACKGROUND: The aim of this study was to evaluate, in particular, whether bone
      resorption occurred at the extraction sites of a group of patients under
      orthodontic treatment, and, in general, whether extraction treatment predisposes
      patients to a greater degree of root resorption. METHODS: The study group
      comprised 12 class II division 1 malocclusion patients who underwent orthodontic
      treatment and extraction, and the control group comprised 10 class II division 1
      patients who underwent orthodontic treatment without extraction. In both groups,
      treatments were carried out by the same operator using the same techniques. Cone
      beam computed tomography performed before (T1) and after (T2) treatment was used
      to determine and compare the root length, the distance from the cementoenamel
      junction to the base of the defect and to the bone peak, the width of the defect
      and the buccolingual bone thickness. RESULTS: Root length was reduced following
      treatment in both groups, although to a statistically significantly greater
      extent in the study group. The buccolingual bone thickness was reduced after
      treatment in both groups, with no differences found between the study and control
      groups. The bone loss at the sites assessed was greater in the patients after
      extraction treatment, with a statistically significant difference revealed
      between the two groups. The site that showed the greatest variation in both
      groups was distal to the upper canines. CONCLUSIONS: In the present study,
      extractive orthodontic treatment appeared to predispose patients to a greater
      degree of root resorption. Indeed, the bone at the extraction site showed greater
      resorption in the study group with respect to the control group, and the
      appearance of intraosseous defects was noted in the former.

PMID- 24326145
TI  - Diagnosis and management of temperature abnormality in ICUs: a EUROBACT
      investigators' survey.
AB  - INTRODUCTION: Although fever and hypothermia are common abnormal physical signs
      observed in patients admitted to intensive care units (ICU), little data exist on
      their optimal management. The objective of this study was to describe
      contemporary practices and determinants of management of temperature
      abnormalities among patients admitted to ICUs. METHODS: Site leaders of the multi
      national EUROBACT study were surveyed regarding diagnosis and management of
      temperature abnormalities among patients admitted to their ICUs. RESULTS: Of the
      162 ICUs originally included in EUROBACT, responses were received from 139 (86%)
      centers in 23 countries in Europe (117), South America (8), Asia (5), North
      America (4), Australia (3) and Africa (2). A total of 117 (84%) respondents
      reported use of a specific temperature threshold in their ICU to define fever. A
      total of 14 different discrete levels were reported with a median of 38.2 degrees
      C (inter-quartile range, IQR, 38.0 degrees C to 38.5 degrees C). The use of
      thermometers was protocolized in 91 (65%) ICUs and a wide range of methods were
      reportedly used, with axillary, tympanic and urinary bladder sites as the most
      common as primary modalities. Only 31 (22%) of respondents indicated that there
      was a formal written protocol for temperature control among febrile patients in
      their ICUs. In most or all cases practice was to control temperature, to use
      acetaminophen, and to perform a full septic workup in febrile patients and that
      this was usually directed by physician order. While reported practice was to
      treat nearly all patients with neurological impairment and most patients with
      acute coronary syndromes and infections, severe sepsis and septic shock, this was
      not the case for most patients with liver failure and fever. CONCLUSIONS: A wide
      range of definitions and management practices were reported regarding temperature
      abnormalities in the critically ill. Documenting temperature abnormality
      management practices, including variability in clinical care, is important to
      inform planning of future studies designed to optimize infection and temperature
      management strategies in the critically ill.

PMID- 24326151
TI  - Assessment of childhood overweight and obesity: any better and feasible tool
      other than body mass index?

PMID- 24326152
TI  - An Important Finding of Systemic Aspergillosis: Skin Involvement and Amphotericin
      B Resistance in an Adolescent.
AB  - Invasive aspergillosis is a life-threatening infectious complication in
      immunocompromised patients, especially with malignancy, and in some cases, it
      causes extensive tissue destruction and subsequent systemic illness, leading to
      multiorgan failure and death. Skin involvement and amphotericin B resistance are
      very rare findings of aspergillosis. Herein, we report the case of a primary
      hemophagocytic syndrome patient who developed subcutaneous nodules in the 3(rd)
      month of bone marrow transplantation from which Aspergillus fumigatus was
      cultivated despite the fact that she was under antifungal therapy. In
      immunocompromised patients with prolonged fever, atypical presentations of
      invasive mycosis should be kept in mind, and early appropriate therapy should be
      initiated promptly to decrease morbidity and mortality.

PMID- 24326153
TI  - Is it accurate to separate glucose-6-phosphate dehydrogenase activity in neonatal
      hyperbilirubinemia as deficient and normal?
AB  - BACKGROUND: The aim of this study was to investigate glucose 6-phosphate
      dehydrogenase (G6PD) activity in term and late preterm babies with severe
      neonatal hyperbilirubinemia and its relationship to the severity and treatment of
      this disorder, regardless of level of G6PD activity (deficient/normal). METHODS:
      A total of 529 term and late preterm (>=35 weeks) infants (228 female, 301 male)
      who were diagnosed with severe hyperbilirubinemia were included in this study. In
      each case, serum was collected to evaluate blood group, direct Coombs' test,
      complete blood cell count, total and direct bilirubin, thyroid-stimulating
      hormone, and G6PD activity. A partial correlation analysis was carried out to
      assess the relationship between G6PD activity and total bilirubin levels.
      RESULTS: A significant correlation was found between the severity of
      hyperbilirubinemia and G6PD activity in both males and females. Male neonates who
      had G6PD levels <12 U/g Hb required more phototherapy time than neonates who had
      G6PD levels >=12 U/g Hb; and female neonates who had G6PD levels <16 U/g Hb
      required more phototherapy time than neonates who had G6PD levels >=16 U/g Hb (p
      < 0.0001). When we analyzed only breastfed infants, a significant difference also
      emerged in both sexes. Decreased G6PD activity was associated with increased
      phototherapy time and the need for exchange transfusion. CONCLUSION: Routine
      checks of G6PD level in hyperbilirubinemic neonates are very important in
      providing proper medical management to prevent bilirubin-induced neurological
      dysfunction. Appropriate identification of G6PD (<12 U/g Hb for male infants and
      <16 U/g Hb for female infants) raises awareness of the severity of the condition
      and the necessity for immediate care of severe hyperbilirubinemic infants.

PMID- 24326154
TI  - Olive oil compounds inhibit vascular endothelial growth factor receptor-2
      phosphorylation.
AB  - Vascular endothelial growth factor (VEGF) triggers crucial signaling processes
      that regulate tumor angiogenesis and, therefore, represents an attractive target
      for the development of novel anticancer therapeutics. Several epidemiological
      studies have confirmed that abundant consumption of foods from plant origin is
      associated with reduced risk of developing cancers. In the Mediterranean basin,
      the consumption of extra virgin olive oil is an important constituent of the
      diet. Compared to other vegetable oils, the presence of several phenolic
      antioxidants in olive oil is believed to prevent the occurrence of a variety of
      pathological processes, such as cancer. While the strong antioxidant potential of
      these molecules is well characterized, their antiangiogenic activities remain
      unknown. The aim of this study is to investigate whether tyrosol (Tyr),
      hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five
      compounds contained in extra virgin olive oil, can affect in vitro angiogenesis.
      We found that HT, Tax and OA were the most potent angiogenesis inhibitors through
      their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951,
      Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC)
      signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly
      reduced VEGF-induced EC proliferation and migration as well as their morphogenic
      differentiation into capillary-like tubular structures in Matrigel. Our study
      demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2
      signaling pathway. These findings emphasize the chemopreventive properties of
      olive oil and highlight the importance of nutrition in cancer prevention. 

PMID- 24326155
TI  - Peritoneal full-conditioning reduces postoperative adhesions and pain: a
      randomised controlled trial in deep endometriosis surgery.
AB  - BACKGROUND: To translate the concept of full-conditioning (FC) from animal
      experiments to the human, and to evaluate the efficacy for adhesion prevention.
      FC consisted of decreasing acute inflammation by 86% CO2+ 10% N2O + 4% O2 for the
      pneumoperitoneum, cooling of the peritoneal cavity, humidification, heparinized
      rinsing solution and 5 mg of dexamethasone as demonstrated in animal models.
      METHODS: A randomized controlled trial (RCT: NCT01344486) comparing standard
      laparoscopy with full conditioning together with a barrier in a 2/3 ratio in 44
      women undergoing deep endometriosis surgery at KULeuven. The primary aim was
      reduction of adhesions. Secondary aims were CO2 resorption, postoperative pain
      and recovery. Randomization was performed after signing informed consent.
      Adhesion scoring during second look laparoscopy and pain scoring were done
      blindly. RESULTS: In the FC group (n = 16) adhesions were completely prevented in
      12/16 women whereas in the control group (n = 11) all women had severe adhesions
      (P < 0.0005). Also the area, density and severity of adhesions were less. (P
      <0.001). In the control group, severity, density and area of adhesions were
      strongly interrelated (P = 0.0001 for all areas) suggesting a common enhancing
      factor. In the FC group CO2 resorption (P < 0.001), postoperative pain (P <
      0.001), and CRP concentrations (P < 0.01) were lower while clinical recovery was
      faster (P < 0.0001) and time to first flatus (P < 0.002) shorter. IN CONCLUSION:
      This translational research confirms in the human the efficacy of FC in reducing
      CO2 resorption and adhesions with in addition less postoperative pain, lower
      postoperative CRP concentrations and an accelerated recovery.

PMID- 24326156
TI  - MicroRNA-21 expression is associated with overall survival in patients with
      glioma.
AB  - BACKGROUND: MicroRNA-21 has been proved to be associated with glioma
      proliferation and invasion; thus, we sought to clarify the clinical value of miR
      21 expression in glioma tissues with WHO grade I to IV. METHODS: One hundred and
      fifty-two pairs of human gliomas and non-neoplastic brain tissues were evaluated
      using real-time PCR. The association of miR-21 expression with
      clinicopathological factors or the prognosis of glioma patients was also
      analyzed. In this study, survival analysis was performed using the Kaplan-Meier
      method and Cox's proportional hazards model. RESULTS: MiR-21 was more greatly
      expressed in glioma tissues compared to the corresponding non-neoplastic brain
      tissues (P < 0.001). This observed high miR-21 expression was significantly
      associated with high pathological grades and the Karnofsky performance score of
      glioma patients. In addition, overall patient survival for those with low miR-21
      expression was significantly longer than those patients with high miR-21
      expression (P < 0.001). Moreover, multivariate Cox regression analysis indicated
      that miR-21 might be an independent prognostic marker for glioma patient
      survival. CONCLUSIONS: Our data show that miR-21 may be a candidate independent
      marker for gliomas, especially those with high pathological grades, and this
      could also be a potential therapeutic target for molecular glioma therapy.
      VIRTUAL SLIDE: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1445749171109834.

PMID- 24326157
TI  - Oxidative stress in children and adolescents with anxiety disorders.
AB  - BACKGROUND: Anxiety disorders are common in children and adolescents, and they
      can significantly impair quality of life. Genetic, neurobiological,
      neurochemical, and psychological factors are believed to play a role in the
      etiopathogenesis of anxiety disorders. Recent evidence suggests that the
      pathophysiology of anxiety disorders may be associated with oxidative stress. In
      this study, we investigated whether there are associations between children with
      anxiety disorders and total oxidant/antioxidant status. METHODS: The experimental
      group consisted of 40 patients (children and adolescents) with anxiety disorders.
      An age- and gender-matched control group composed of 35 healthy subjects was also
      assessed. Venous blood samples were collected and total antioxidative status
      (TAS), total oxidative status (TOS), and the oxidative stress index (OSI) were
      determined. RESULTS: Both the TOS and the OSI of the experimental group were
      significantly higher than those of the control group. There were no significant
      differences in TAS between the experimental and control groups. LIMITATIONS: The
      main limitation of our study was the small sample size. CONCLUSIONS: This study
      suggests that oxidative balance is impaired in children with anxiety disorders.
      Oxidative stress may play a role in the etiopathogenesis of anxiety disorders,
      and TOS may be a useful diagnostic tool in this context.

PMID- 24326159
TI  - Sustainable design for automotive products: dismantling and recycling of end-of
      life vehicles.
AB  - The growth in automotive production has increased the number of end-of-life
      vehicles (ELVs) annually. The traditional approach ELV processing involves
      dismantling, shredding, and landfill disposal. The "3R" (i.e., reduce, reuse, and
      recycle) principle has been increasingly employed in processing ELVs,
      particularly ELV parts, to promote sustainable development. The first step in
      processing ELVs is dismantling. However, certain parts of the vehicle are
      difficult to disassemble and use in practice. The extended producer
      responsibility policy requires carmakers to contribute in the processing of scrap
      cars either for their own developmental needs or for social responsibility. The
      design for dismantling approach can be an effective solution to the existing
      difficulties in dismantling ELVs. This approach can also provide guidelines in
      the design of automotive products. This paper illustrates the difficulty of
      handling polymers in dashboards. The physical properties of polymers prevent easy
      separation and recycling by using mechanical methods. Thus, dealers have to rely
      on chemical methods such as pyrolysis. Therefore, car designers should use a
      single material to benefit dealers. The use of materials for effective end-of
      life processing without sacrificing the original performance requirements of the
      vehicle should be explored. 

PMID- 24326158
TI  - A simple three-dimensional stent for proper placement of mini-implant.
AB  - BACKGROUND: This paper deals with the fabrication of a three-dimensional stent
      which is simple in design but provides an accurate placement of a mini-implant in
      three planes of space, namely, sagittal (root proximity), vertical (attached
      gingiva/alveolar mucosa) and transverse (angulation). FINDINGS: The stent is made
      of 0.018*0.025 in. stainless steel archwire which consists of a 'u loop'
      angulated at 20 degrees , a vertical limb, a horizontal limb and a stop. The
      angulation of the 'u' helps in the placement of the mini-implant at 70 degrees 
      to the long axis of the tooth. The vertical height is determined such that the
      mini-implant is placed at the mucogingival junction. The mini-implant is placed
      with the aid of the stent, and its angulation and proximity to the adjacent roots
      are checked with a cone beam computed tomography image. The cone beam computed
      tomography image showed the mini-implant at an angle of 70 degrees  to the long
      axis of the tooth. There is no contact between mini-implant and the roots of the
      adjacent teeth. CONCLUSION: This stent is simple, easy to fabricate, cost
      effective, and provides ease of insertion/removal, and three-dimensional
      orientation of the mini-implant.

PMID- 24326160
TI  - Inventory and treatment of compost maturation emissions in a municipal solid
      waste treatment facility.
AB  - Emissions of volatile organic compounds (VOCs) from the compost maturation
      building in a municipal solid waste treatment facility were inventoried by solid
      phase microextraction and gas chromatography-mass spectrometry. A large diversity
      of chemical classes and compounds were found. The highest concentrations were
      found for n-butanol, methyl ethyl ketone and limonene (ppmv level). Also, a range
      of compounds exceeded their odor threshold evidencing that treatment was needed.
      Performance of a chemical scrubber followed by two parallel biofilters packed
      with an advanced packing material and treating an average airflow of 99,300 m(3)
      h(-1) was assessed in the treatment of the VOCs inventoried. Performance of the
      odor abatement system was evaluated in terms of removal efficiency by comparing
      inlet and outlet abundances. Outlet concentrations of selected VOCs permitted to
      identify critical odorants emitted to the atmosphere. In particular, limonene was
      found as the most critical VOC in the present study. Only six compounds from the
      odorant group were removed with efficiencies higher than 90%. Low removal
      efficiencies were found for most of the compounds present in the emission showing
      a significant relation with their chemical properties (functionality and
      solubility) and operational parameters (temperature, pH and inlet concentration).
      Interestingly, benzaldehyde and benzyl alcohol were found to be produced in the
      treatment system.

PMID- 24326161
TI  - Intake of dietary phylloquinone and menaquinones and risk of stroke.
AB  - BACKGROUND: Dietary vitamin K intake is thought to decrease the risk of
      cardiovascular disease (CVD) by reducing vascular calcification, although vitamin
      K is also involved in coagulation. Studies investigating the association between
      phylloquinone intake and risk of stroke are scarce, and the relation with
      menaquinones has not been investigated to date. METHODS AND RESULTS: We
      investigated the association between intake of phylloquinone and menaquinones and
      stroke in a prospective cohort of 35,476 healthy subjects. Information on
      occurrence of stroke was obtained by linkage to national registries, and stroke
      was further specified into ischemic and hemorrhagic stroke. Vitamin K intake was
      estimated using a validated food-frequency questionnaire. Multivariate Cox
      proportional hazards models adjusted for cardiovascular risk factors, lifestyle,
      and other dietary factors were used to estimate the associations. During a follow
      up of 12.1 +/- 2.1 years, 580 incident cases of stroke were identified, 163 of
      which were hemorrhagic and 324 were ischemic. Phylloquinone intake was not
      associated with risk of stroke with a hazard ratio (HR) of 1.09 (95% CI: 0.85 to
      1.40, P(trend) 0.41) for the highest versus lowest quartile. For intake of
      menaquinones similar results were found, with an HR(Q4 versus Q1) of 0.99 (95%
      CI: 0.75 to 1.29, P(trend) 0.82). When specifying hemorrhagic and ischemic stroke
      or menaquinone subtypes, no significant associations were detected. CONCLUSION:
      In our study, neither dietary phylloquinone nor dietary menaquinones intake were
      associated with stroke risk.

PMID- 24326162
TI  - Activation of hypoxia-inducible factor-2 in adipocytes results in pathological
      cardiac hypertrophy.
AB  - BACKGROUND: Obesity can cause structural and functional abnormalities of the
      heart via complex but largely undefined mechanisms. Emerging evidence has shown
      that obesity results in reduced oxygen concentrations, or hypoxia, in adipose
      tissue. We hypothesized that the adipocyte hypoxia-signaling pathway plays an
      essential role in the development of obesity-associated cardiomyopathy. METHODS
      AND RESULTS: Using a mouse model in which the hypoxia-inducible factor (HIF)
      pathway is activated by deletion of the von Hippel-Lindau gene specifically in
      adipocytes, we found that mice with adipocyte-von Hippel-Lindau deletion
      developed lethal cardiac hypertrophy. HIF activation in adipocytes results in
      overexpression of key cardiomyopathy-associated genes in adipose tissue,
      increased serum levels of several proinflammatory cytokines including interleukin
      1beta and monocyte chemotactic protein-1, and activation of nuclear factor-kappaB
      and nuclear factor of activated T cells in the heart. Interestingly, genetic
      deletion of Hif2a, but not Hif1a, was able to rescue cardiac hypertrophy and
      abrogate adipose inflammation. CONCLUSION: We have discovered a previously
      uncharacterized mechanism underlying a critical and direct role of the adipocyte
      HIF-2 transcription factor in the development of adipose inflammation and
      pathological cardiac hypertrophy.

PMID- 24326164
TI  - An integrated approach to evaluating alternative risk prediction strategies: a
      case study comparing alternative approaches for preventing invasive fungal
      disease.
AB  - OBJECTIVES: This article proposes an integrated approach to the development,
      validation, and evaluation of new risk prediction models illustrated with the
      Fungal Infection Risk Evaluation study, which developed risk models to identify
      non-neutropenic, critically ill adult patients at high risk of invasive fungal
      disease (IFD). METHODS: Our decision-analytical model compared alternative
      strategies for preventing IFD at up to three clinical decision time points
      (critical care admission, after 24 hours, and end of day 3), followed with
      antifungal prophylaxis for those judged "high" risk versus "no formal risk
      assessment." We developed prognostic models to predict the risk of IFD before
      critical care unit discharge, with data from 35,455 admissions to 70 UK adult,
      critical care units, and validated the models externally. The decision model was
      populated with positive predictive values and negative predictive values from the
      best-fitting risk models. We projected lifetime cost-effectiveness and expected
      value of partial perfect information for groups of parameters. RESULTS: The risk
      prediction models performed well in internal and external validation. Risk
      assessment and prophylaxis at the end of day 3 was the most cost-effective
      strategy at the 2% and 1% risk threshold. Risk assessment at each time point was
      the most cost-effective strategy at a 0.5% risk threshold. Expected values of
      partial perfect information were high for positive predictive values or negative
      predictive values (L11 million-L13 million) and quality-adjusted life-years (L11
      million). CONCLUSIONS: It is cost-effective to formally assess the risk of IFD
      for non-neutropenic, critically ill adult patients. This integrated approach to
      developing and evaluating risk models is useful for informing clinical practice
      and future research investment.

PMID- 24326163
TI  - Cortical synaptic NMDA receptor deficits in alpha7 nicotinic acetylcholine
      receptor gene deletion models: implications for neuropsychiatric diseases.
AB  - Microdeletion of the human CHRNA7 gene (alpha7 nicotinic acetylcholine receptor,
      nAChR) as well as dysfunction in N-methyl-d-aspartate receptors (NMDARs) have
      been associated with cortical dysfunction in a broad spectrum of
      neurodevelopmental and neuropsychiatric disorders including schizophrenia.
      However, the pathophysiological roles of synaptic vs. extrasynaptic NMDARs and
      their interactions with alpha7 nAChRs in cortical dysfunction remain largely
      uncharacterized. Using a combination of in vivo and in vitro models, we
      demonstrate that alpha7 nAChR gene deletion leads to specific loss of synaptic
      NMDARs and their coagonist, d-serine, as well as glutamatergic synaptic deficits
      in mouse cortex. alpha7 nAChR null mice had decreased cortical NMDAR expression
      and glutamatergic synapse formation during postnatal development. Similar
      reductions in NMDAR expression and glutamatergic synapse formation were revealed
      in cortical cultures lacking alpha7 nAChRs. Interestingly, synaptic, but not
      extrasynaptic, NMDAR currents were specifically diminished in cultured cortical
      pyramidal neurons as well as in acute prefrontal cortical slices of alpha7 nAChR
      null mice. Moreover, d-serine responsive synaptic NMDAR-mediated currents and
      levels of the d-serine synthetic enzyme serine racemase were both reduced in
      alpha7 nAChR null cortical pyramidal neurons. Our findings thus identify specific
      loss of synaptic NMDARs and their coagonist, d-serine, as well as glutamatergic
      synaptic deficits in alpha7 nAChR gene deletion models of cortical dysfunction,
      thereby implicating alpha7 nAChR-mediated control of synaptic NMDARs and serine
      racemase/d-serine pathways in cortical dysfunction underlying many
      neuropsychiatric and neurodevelopmental disorders, particularly those associated
      with deletion of human CHRNA7. 

PMID- 24326165
TI  - Mifamurtide for high-grade, resectable, nonmetastatic osteosarcoma following
      surgical resection: a cost-effectiveness analysis.
AB  - OBJECTIVES: Mifamurtide is an immune macrophage stimulant that when added to
      standard chemotherapy has demonstrated survival benefit for newly diagnosed
      osteosarcoma. The objectives of this study were to investigate the cost
      effectiveness of adding mifamurtide to standard three- or four-agent chemotherapy
      for high-grade, resectable, nonmetastatic osteosarcoma following surgical
      resection and the issues of obtaining robust cost-effectiveness estimates for
      ultra-orphan drugs, given the shortage of data. METHODS: An economic evaluation
      was conducted from the perspective of the UK's National Health Service as part of
      the manufacturer's submission to the National Institute for Health and Care
      Excellence. The disease process was simplified to a transition through a series
      of health states, modeled by using a Markov approach. Data to inform the model
      were derived from patient-level data of Study INT-0133, published literature, and
      expert opinion. The final efficacy measure was life-years gained (LYG), and
      utilities were used to obtain quality-adjusted life-years (QALYs). RESULTS: For a
      60-year time frame and a discount rate of 3.5% for outcomes, patients receiving
      mifamurtide benefited from an average additional 1.57 years of life and 1.34
      QALYs, compared with patients receiving chemotherapy alone, giving an incremental
      cost-effectiveness ratio (ICER) of L58,737 per LYG and L68,734 per QALY. Because
      treatment effects were both substantial in restoring health and sustained over a
      very long period, the National Institute for Health and Care Excellence changed
      its guidance to allow a discount of 1.5% for outcomes to be applied in these
      special circumstances. By using this discount factor, it was found that patients
      receiving mifamurtide had an average additional 2.58 years of life and 2.20 QALYs
      compared with patients receiving chemotherapy alone, resulting in an ICER of
      L35,765 per LYG and L41,933 per QALY. CONCLUSION: Mifamurtide's ICER is cost
      effective compared with that of other orphan and ultra-orphan drugs, for which
      prices and corresponding cost-effectiveness estimates are high.

PMID- 24326166
TI  - A clinical research practice datalink analysis of antidepressant treatment
      patterns and health care costs in generalized anxiety disorder.
AB  - OBJECTIVE: To describe real-life prescription patterns, health care resource use,
      and costs in adults with generalized anxiety disorder (GAD) initiating
      antidepressant (AD) treatment in the United Kingdom. METHODS: A retrospective
      longitudinal cohort study using data from Clinical Research Practice Datalink was
      conducted. Adults with incident prescription of an AD (index date) between
      January 1, 2006, and June 30, 2010, and with a diagnosis of GAD within the 2
      months preceding or following the index date were included. Patients with a
      diagnosis of schizophrenia or bipolar disorder were excluded. RESULTS: A total of
      29,131 patients with GAD were included in the analysis. Their mean age was 48.5
      +/- 15.5 years, and two thirds were women. GAD-licensed ADs (i.e., escitalopram,
      paroxetine, venlafaxine XR, and duloxetine) represented only 12.5% of the index
      AD prescriptions. At least one anxiolytic was prescribed for 23.5% of the
      patients. Only 33.2% of the patients continued index AD treatment over the study
      period. Discontinuation occurred for 46.0% of the patients, after a mean of 3.7
      months of treatment. The health care costs were L338.4 per patient in the 6
      months before the index date and L984.6 in the 9 months after the index date.
      Psychiatric hospitalization (relative risk = 4.18; 95% CI 3.53-4.96; P < 0.001)
      and duloxetine as index treatment (relative risk = 1.85; 95% CI 1.30-2.63; P <
      0.001) were the main determinants of increased costs for these patients.
      CONCLUSIONS: The significant rate of AD discontinuation and associated treatment
      duration indicate unmet needs among patients with GAD. As described in American
      studies, substantial health care costs were also observed in this study.

PMID- 24326167
TI  - Understanding the economic burden of nonsevere nocturnal hypoglycemic events:
      impact on work productivity, disease management, and resource utilization.
AB  - OBJECTIVE: Nonsevere hypoglycemic events are common and may occur in one-third of
      persons with diabetes as often as several times a week. This study's objective
      was to examine the economic burden of nonsevere nocturnal hypoglycemic events
      (NSNHEs). METHODS: A 20-minute Web-based survey, with items derived from the
      literature, expert input, and patient interviews, assessing the impact of NSNHEs
      was administered in nine countries to 18 years and older patients with self
      reported diabetes having an NSNHE in the past month. RESULTS: A total of 20,212
      persons were screened, with 2,108 respondents meeting criteria and included in
      the analysis sample. The cost of lost work productivity per NSNHE was estimated
      to be between $10.21 (Germany) and $28.13 (the United Kingdom), representing 3.3
      to 7.5 hours of lost work time per event. A reduction in work productivity
      (presenteeism) was also reported. Compared with respondents' usual blood sugar
      monitoring practice, on average, 3.6 +/- 6.6 extra tests were conducted in the
      week following the event at a cost of approximately $87.1 per year. Additional
      costs were also incurred for doctor visits as well as medical care required
      because of falls or injuries incurred during the NSNHE for an annual cost of
      $2,111.3 per person per year. When taking into consideration the multiple impacts
      of NSNHEs for the total sample and the frequency that these events occur, the
      resulting total annual economic burden was $288,000 or $127 per person per event.
      CONCLUSIONS: NSNHEs have serious consequences for patients. Greater attention to
      treatments that reduce NSNHEs can have a major impact on reducing the economic
      burden of diabetes.

PMID- 24326168
TI  - Assessment of PRO label claims granted by the FDA as compared to the EMA (2006
      2010).
AB  - BACKGROUND: The US Food and Drug Administration (FDA) provides formal guidance
      for the use of patient-reported outcomes (PROs) in support of labeling claims,
      whereas the European Medicines Agency (EMA) offers insight in a reflection paper
      relating to health-related quality of life in lieu of formal guidance.
      OBJECTIVES: PRO label claims granted for new molecular entities and biologic
      license applications from 2006 through 2010 were reviewed to evaluate
      consistencies and discrepancies in PRO label claims granted by the FDA and the
      EMA and to highlight trends in the acceptance of PRO claims across agencies.
      METHODS: Products approved by both the FDA and the EMA were identified. By using
      US Drug Approval Packages and European Public Assessment Reports packages, any
      PRO label claims made for the same product by the same company were compared.
      RESULTS: Both agencies approved a total of 75 products. Of these, 35 (47%) had at
      least one EMA-granted PRO label claim compared with 14 (19%) by the FDA. Most FDA
      grated claims focused on symptoms; however, EMA-granted claims were more likely
      to include higher order concepts. Few (~12%) were granted the same label claims.
      Despite this discordance between the two agencies, where PRO label claims were
      granted by both the FDA and the EMA, there was similarity in the type of label
      claim. CONCLUSIONS: The EMA is more likely than the FDA to grant PRO claims and
      for higher order constructs. On a macro level, there appears to be poor
      concordance between claims granted by both agencies. On close examination,
      however, there appears to be greater concordance than previously recognized,
      which may be instructive in formulating future PRO strategies. Further research
      to create strategic alignment across agencies may be beneficial.

PMID- 24326169
TI  - Development of a disease-specific version of the EQ-5D-5L for use in patients
      suffering from psoriasis: lessons learned from a feasibility study in the UK.
AB  - OBJECTIVES: The EuroQol five-dimensional (EQ-5D) questionnaire is a generic
      measure widely used for the assessment of health status. Research has suggested
      that it may be insensitive to the burdens associated with particular conditions.
      This study was designed to explore the feasibility of developing and valuing a
      disease-specific "bolt-on" version of the EQ-5D questionnaire for use in
      psoriasis. METHODS: A series of steps were undertaken to develop, test, and
      evaluate dimensions for a psoriasis-specific version of the EQ-5D questionnaire
      (hereafter referred to as the EQ-PSO questionnaire). Candidate dimensions were
      explored through a review of published literature, in-depth qualitative
      interviews with patients, and consultation with a clinical expert. A psychometric
      validation exercise was then undertaken to establish how well dimensions
      functioned. Two dimensions were selected for inclusion in a draft measure
      alongside the existing EQ-5D questionnaire dimensions: "skin irritation" and
      "self-confidence." Last, a time trade-off valuation exercise was conducted with
      300 members of the UK general public to derive utilities for health states
      described by the measure. RESULTS: The psychometric analyses indicated that the
      two new candidate dimensions captured additional variance over and above the
      existing five dimensions. Data from the valuation exercise were analyzed by using
      different models. A collapsed random effects model was put forward as a
      parsimonious and accurate approach. Based on this model, estimated utilities
      ranged from 0.98 +/- 0.02 for state "1111111" to 0.03 +/- 0.29 for state
      "5555555." CONCLUSIONS: This study has developed the EQ-PSO questionnaire to
      support future psoriasis research and has informed the development of future bolt
      on versions of the EQ-5D questionnaire.

PMID- 24326170
TI  - A pilot study of multicriteria decision analysis for valuing orphan medicines.
AB  - OBJECTIVE: To pilot the use of multicriteria decision analysis to establish and
      apply a framework of weighted attributes to value orphan medicinal products.
      METHODS: Literature searches on the natural history and burden of 40 rare
      diseases and of how payers assess treatment value and three workshops with,
      respectively, GlaxoSmithKline managers working on orphan medicinal products,
      European Union clinical and health economics experts, and representatives of rare
      diseases patient groups in the European Union. RESULTS: Eight nonmonetary
      attributes were identified and weights agreed: four concern the disease being
      treated and four the treatment itself. About half of the weight went to
      attributes of the disease treated and half to attributes of the treatment.
      Patient group representatives gave greater weight than did the experts to
      patients' and carers' quality of daily life. CONCLUSIONS: The multicriteria
      decision analysis approach piloted works and could be developed for use by payers
      and health technology assessment bodies.

PMID- 24326171
TI  - Validation of models that estimate the cost-effectiveness of improving patient
      adherence.
AB  - This note suggests a test for internal validation of models that estimate the
      costs and effects of improving patient adherence. We apply the validation test to
      two published cost-effectiveness models on adherence improvement. 

PMID- 24326172
TI  - The cost-effectiveness of duloxetine in chronic low back pain: a US private payer
      perspective.

PMID- 24326173
TI  - The cost-effectiveness of duloxetine in chronic low back pain: a US private payer
      perspective-author response to letter to the editor.

PMID- 24326174
TI  - Thirteen-week oral dose toxicity study of Oligonol containing oligomerized
      polyphenols extracted from lychee and green tea.
AB  - Oligonol is a functional food containing catechin-type monomers and
      proanthocyanidin oligomer converted from polymer forms via a novel manufacturing
      process. The catechin component of green tea extract has been associated with
      nasal toxicity in rats following subchronic exposure. To assess the potential for
      Oligonol to induce nasal toxicity a 13-week repeated oral dose toxicity study was
      conducted in rats using doses of 100, 300, and 1000 mg/kg/d. Clinical signs and
      mortality were not affected by Oligonol treatment. Compound-colored stools and an
      increase in food consumption were observed in some treated groups; however, there
      were no treatment-related differences in terminal body weights or with respect to
      the results of the gross postmortem examinations. Histopathological evaluation of
      the nasal cavity tissues revealed no treatment-related lesions. The results from
      this toxicity study indicate that Oligonol does not induce nasal toxicity and
      further supports the results of previous studies demonstrating the safety of
      Oligonol for human consumption.

PMID- 24326175
TI  - Monitoring treatment response in abdominal sepsis with procalcitonin--if only!
AB  - The ideal management of infection includes not only the early identification and
      start of effective therapy but also the correct categorization of non-infected
      patients in order to avoid unnecessary use of antimicrobials. The availability of
      a specific and sensitive test for the presence of infection is of paramount
      importance to improve the prudent use of antimicrobial therapy. Procalcitonin
      (PCT) has been evaluated over recent years as to whether it can be used to detect
      the presence of different types of infection, allows reduced duration of
      antibiotic therapy, or predicts treatment failure or adverse outcome. In the
      previous issue of Critical Care, Jung and colleagues report about the monitoring
      of treatment response in abdominal sepsis by repetitive determination of PCT. 

PMID- 24326176
TI  - Effects of cyclic loading on the shear bond strength of metal orthodontic
      brackets bonded to resin composite veneer surface using different conditioning
      protocols.
AB  - BACKGROUND: The aim of this research is to evaluate cyclic (CSBS) and static
      shear bond strengths (SSBS) of metal orthodontic brackets bonded to composite
      laminates using different conditioning protocols. METHODS: A total of 80 direct
      nanofilled composite laminate veneers were prepared on permanent incisors and
      divided into four equal groups according to different surface treatments. In
      group 1, diamond bur was used. In group 2, microetcher (50-MUm alumina particles)
      was utilized. In group 3, 38% phosphoric acid treatment for 60 s was done. In
      group 4 (control group), metal brackets were bonded to the untreated veneer
      surfaces using no-mix adhesive resin. SSBS testing was carried out for ten
      specimens, while CSBS testing was done for another ten specimens from each group.
      The data were subjected to analysis of variance and Scheffe post hoc test. The
      chi-square test was used to determine significant differences in the adhesive
      remnant index scores among different groups. RESULTS: Statistically significant
      difference was only found between SSBS of brackets bonded when surface treatment
      was done using the diamond bur, microetcher, and the phosphoric acid at P<0.05.
      With regard to CSBS, the use of bur treatment and microetching achieved the
      highest values; however, there was no significant difference between these two
      groups. With phosphoric acid, surface treatment achieved the lowest CSBS value;
      there was no significant difference between this group and the control group. The
      SSBS was significantly higher than CSBS in all groups. CONCLUSIONS: Roughening
      composite laminate veneers with either diamond bur or microetcher could be used
      successfully as an alternative to provide higher bond strength than phosphoric
      acid surface treatment. Cyclic loading significantly decreased bond strength.

PMID- 24326177
TI  - A new intranuclear microsporidium, Enterospora nucleophila n. sp., causing an
      emaciative syndrome in a piscine host (Sparus aurata), prompts the redescription
      of the family Enterocytozoonidae.
AB  - The presence of a new microsporidium is believed to be responsible for an
      emaciative syndrome observed in farmed gilthead sea bream (Sparus aurata) from
      different facilities along the Spanish coast. Infected fish were approximately
      half the average weight and significant mortality was attributed to the condition
      in some facilities. Clinical signs included anorexia, cachexia and pale internal
      organs. The microsporidium was found mainly in the intestinal mucosa and
      occasionally in the submucosa. Morphological, histopathological, ultrastructural
      and molecular phylogenetic studies were conducted to characterise this organism.
      This microsporidium undergoes intranuclear development in rodlet cells and
      enterocytes, and cytoplasmic development mainly in enterocytes and macrophages.
      The nucleus-infecting plasmodium contains several diplokarya and displays
      polysporous development which occurs without an interfacial envelope. In the host
      cell cytoplasm, the parasite develops within a membrane-bound matrix. In both
      infection locations, the polar tube precursors appear as disks, first with lucent
      centres, then as fully dense disks as they fuse to form the polar filament, all
      before division of the plasmodium into sporoblasts. Up to 16 intranuclear spores
      result from the sporogonic development of a single plasmodium, whereas more than
      40 spores result from several asynchronous reproductive cycles in the cytoplasmic
      infection. Fixed spores are ellipsoidal and diplokaryotic, with five to six coils
      of an isofilar polar filament in a single row. ssrDNA-based molecular
      phylogenetic inference places this parasite as a sister clade to crustacean
      infecting species of the Enterocytozoonidae and closer to Enterocytozoon bieneusi
      than to other fish-infecting microsporidians presenting intranuclear development,
      i.e. Nucleospora, Paranucleospora and Desmozoon. Our studies result in the
      erection of a new species, Enterospora nucleophila, within the family
      Enterocytozoonidae, and the description of this family is amended accordingly to
      accommodate the features of known species assigned to it. Severe
      histopathological damage occurs in intense infections and this microsporidian is
      considered a serious emerging threat in sea bream production. 

PMID- 24326179
TI  - Electronic medical record: research tool for pancreatic cancer?
AB  - BACKGROUND: A novel data warehouse based on automated retrieval from an
      institutional health care information system (HIS) was made available to be
      compared with a traditional prospectively maintained surgical database. METHODS:
      A newly established institutional data warehouse at a single-institution academic
      medical center autopopulated by HIS was queried for International Classification
      of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes for
      pancreatic neoplasm. Patients with ICD-9-CM diagnosis codes for pancreatic
      neoplasm were captured. A parallel query was performed using a prospective
      database populated by manual entry. Duplicated patients and those unique to
      either data set were identified. All patients were manually reviewed to determine
      the accuracy of diagnosis. RESULTS: A total of 1107 patients were identified from
      the HIS-linked data set with pancreatic neoplasm from 1999-2009. Of these, 254
      (22.9%) patients were also captured by the surgical database, whereas 853 (77.1%)
      patients were only in the HIS-linked data set. Manual review of the HIS-only
      group demonstrated that 45.0% of patients were without identifiable pancreatic
      pathology, suggesting erroneous capture, whereas 36.3% of patients were
      consistent with pancreatic neoplasm and 18.7% with other pancreatic pathology. Of
      the 394 patients identified by the surgical database, 254 (64.5%) patients were
      captured by HIS, whereas 140 (35.5%) patients were not. Manual review of patients
      only captured by the surgical database demonstrated 85.9% with pancreatic
      neoplasm and 14.1% with other pancreatic pathology. Finally, review of the 254
      patient overlap demonstrated that 80.3% of patients had pancreatic neoplasm and
      19.7% had other pancreatic pathology. CONCLUSIONS: These results suggest that
      cautious interpretation of administrative data rely only on ICD-9-CM diagnosis
      codes and clinical correlation through previously validated mechanisms.

PMID- 24326178
TI  - Cellular localization of protein arginine methyltransferase-5 correlates with
      grade of lung tumors.
AB  - BACKGROUND: Protein arginine methyltransferase-5 (PRMT5) is a chromatin-modifying
      enzyme capable of methylating histone and non-histone proteins, and is involved
      in a wide range of cellular processes that range from transcriptional regulation
      to organelle biosynthesis. As such, its overexpression has been linked to tumor
      suppressor gene silencing, enhanced tumor cell growth and survival. MATERIAL AND
      METHODS: Quantitative real-time polymerase chain reaction, Western immunoblot and
      immunohistochemistry were used to characterize PRMT5 expression in lung cancer
      cell lines and human tumors. Clinicopathological findings of tissue microarray
      based samples from 229 patients with non-small cell lung carcinomas (NSCLC) and
      133 cases with pulmonary neuroendocrine tumors (NET) were analyzed with regard to
      nuclear and cytoplasmic PRMT5 expression. RESULTS: There was statistically
      significant difference in PRMT5 messenger RNA expression between tumors and
      nonneoplastic lung tissues. Immunoblot experiments showed abundant expression of
      PRMT5 and its symmetric methylation mark H4R3 in lung carcinoma but not in non
      neoplastic human pulmonary alveolar and bronchial epithelial cell lines. More
      than two thirds of lung tumors expressed PRMT5. High levels of cytoplasmic PRMT5
      were detected in 20.5% of NSCLC and in 16.5% of NET; high levels of nuclear PRMT5
      were detected in 38.0% of NSCLC and 24.0% of NET. Cytoplasmic PRMT5 was
      associated with high grade in both NSCLC and pulmonary NET while nuclear PRMT5
      was more frequent in carcinoid tumors (p < 0.05). CONCLUSION: The observed
      findings support the role of PRMT5 in lung tumorigenesis and reflect its
      functional dichotomy in cellular compartments. VIRTUAL SLIDE: The virtual slides
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1611895162102528.

PMID- 24326180
TI  - The power to resist: the relationship between power, stigma, and negative
      symptoms in schizophrenia.
AB  - Stigmatizing beliefs about mental illness can be a daily struggle for people with
      schizophrenia. While investigations into the impact of internalizing stigma on
      negative symptoms have yielded mixed results, resistance to stigmatizing beliefs
      has received little attention. In this study, we examined the linkage between
      internalized stigma, stigma resistance, negative symptoms, and social power, or
      perceived ability to influence others during social interactions among people
      with schizophrenia. Further, we sought to determine whether resistance to stigma
      would be bolstered by social power, with greater power in relationships with
      other possibly buffering against motivation/pleasure negative symptoms. Fifty-one
      people with schizophrenia or schizoaffective disorder completed measures of
      social power, internalized stigma, and stigma resistance. Negative symptoms were
      assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS).
      Greater social power was associated with less internalized stigma and negative
      symptoms as well as more stigma resistance. Further, the relationship between
      social power and negative symptoms was partially mediated by stigma resistance.
      These findings provide evidence for the role of stigma resistance as a viable
      target for psychosocial interventions aimed at improving motivation and social
      power in people with schizophrenia. 

PMID- 24326181
TI  - Predicting mandibular growth increment on the basis of cervical vertebral
      dimensions in Iranian girls.
AB  - BACKGROUND: The purpose of this longitudinal study was to establish an equation
      to predict incremental mandibular length on the basis of the analysis of the
      cervical vertebrae on a single cephalometric radiograph and to compare the
      predictive accuracy with the method by Mito et al. METHODS: Data consist of a
      group of 33 Iranian girls, 9 to 11 years old with two lateral cephalometric
      radiographs taken at a 24-month interval. For each individual, on the lateral
      cephalometric radiographs, points and lines for the description of the
      morphologic characteristics of the third and fourth cervical vertebral bodies
      were traced and measured. The real mandibular length increment (MLI) in this
      period was determined by the difference between the second (24 months) and first
      (baseline) radiographs: MLI=Ar-Pog (second)-Ar-Pog (first). An equation was
      determined to calculate mandibular length increments on the basis of the
      measurements in the third and fourth cervical vertebral bodies. The predictive
      accuracy was assessed using multiple regression analysis. RESULTS: The adjusted
      R2 for this equation was 54.9% which is a reliable value for evaluating
      prediction accuracy .The average error between the predicted increment and the
      actual increment was 0.149 mm for our method and 5.87 mm for the method by Mito
      et al. DISCUSSION: There are two items that contributed to easier and better
      prediction accuracy in our equation: (1) higher R2 and (2) fewer independent
      variables. In our subjects, the prediction accuracy was lower when using Mito et
      al.'s method, which could be due to genetic and environmental factors and
      selected age range. CONCLUSION: These results indicate that cervical vertebral
      measurements, obtained in lateral cephalograms, are able to predict properly the
      mandibular growth potential.

PMID- 24326182
TI  - Glycaemic index: did Health Canada get it wrong? Position from the International
      Carbohydrate Quality Consortium (ICQC).

PMID- 24326183
TI  - Serum IGF-1 levels as a clinical tool for optimizing orthodontic treatment
      timing.
AB  - BACKGROUND: The study aims to associate serum insulin-like growth factor-1 (IGF
      1) levels with cervical maturation stages (CS) 3, 4, and 5 on lateral cephalogram
      in male subjects and to find out peak serum IGF-1 levels among these three
      stages. METHODS: The study was conducted on 45 male subjects who were at skeletal
      maturation stage CS-3, CS-4, and CS-5. Subjects were selected using simple random
      sampling technique. Serum IGF-1 levels were estimated from blood samples using
      chemiluminescence immunoassay (CLIA) method. CS was evaluated using a six-stage
      method of evaluating the cervical vertebrae. Mean IGF-1 levels between the stages
      were compared by analysis of variance (ANOVA) test. RESULTS: One-way ANOVA showed
      highly significant differences between all cervical stages with p value<0.01, but
      post hoc Tukey test showed highly significant differences between CS-4 and CS-5
      with p value 0.006. Serum IGF-1 levels showed good association with skeletal age
      in male subjects; 53.3% of subjects at CS-3, 66.7% subjects at CS-4, and 6.7%
      subjects at CS-5 showed IGF-1 levels in peak range. CONCLUSIONS: Serum IGF levels
      can be used as an additional tool to optimize orthodontic treatment timing.

PMID- 24326184
TI  - Choice alters Drosophila oviposition site preference on menthol.
AB  - Food choice and preference relies on multiple sensory systems that are under the
      control of genes and sensory experience. Exposure to specific nutrients and
      nutrient-related molecules can change food preference in vertebrates and
      invertebrates. For example, larval exposure of several holometabolous insects to
      menthol can change their adult response to this molecule. However, studies
      involving Drosophila melanogaster exposure to menthol produced controversial
      results due maybe to methodological differences. Here, we compared the
      oviposition-site preference of wild-type D. melanogaster lines freely or forcibly
      exposed to menthol-rich food. After 12 generations, oviposition-site preference
      diverged between the two lines. Counterintuitively, menthol 'forced' lines showed
      a persistent aversion to menthol whereas 'free choice' lines exhibited a
      decreased aversion to menthol-rich food. This effect was specific to menthol
      since the 'free choice' lines showed unaltered responses to caffeine and sucrose.
      This suggests that the genetic factors underlying Drosophila oviposition site
      preference are more rapidly influenced when flies have a choice between
      alternative sources compared to flies permanently exposed to the same aversive
      substance. 

PMID- 24326185
TI  - Yeast RAD2, a homolog of human XPG, plays a key role in the regulation of the
      cell cycle and actin dynamics.
AB  - Mutations in the human XPG gene cause Cockayne syndrome (CS) and xeroderma
      pigmentosum (XP). Transcription defects have been suggested as the fundamental
      cause of CS; however, defining CS as a transcription syndrome is inconclusive. In
      particular, the function of XPG in transcription has not been clearly
      demonstrated. Here, we provide evidence for the involvement of RAD2, the
      Saccharomyces cerevisiae counterpart of XPG, in cell cycle regulation and
      efficient actin assembly following ultraviolet irradiation. RAD2 C-terminal
      deletion, which resembles the XPG mutation found in XPG/CS cells, caused cell
      growth arrest, the cell cycle stalling, a defective alpha-factor response,
      shortened lifespan, cell polarity defect, and misregulated actin-dynamics after
      DNA damage. Overexpression of the C-terminal 65 amino acids of Rad2p was
      sufficient to induce hyper-cell polarization. In addition, RAD2 genetically
      interacts with TPM1 during cell polarization. These results provide insights into
      the role of RAD2 in post-UV irradiation cell cycle regulation and actin assembly,
      which may be an underlying cause of XPG/CS. 

PMID- 24326186
TI  - Mutagenesis and homologous recombination in Drosophila cell lines using
      CRISPR/Cas9.
AB  - We have applied the CRISPR/Cas9 system to Drosophila S2 cells to generate
      targeted genetic mutations in more than 85% of alleles. By targeting a
      constitutive exon of the AGO1 gene, we demonstrate homozygous mutation in up to
      82% of cells, thereby allowing the study of genetic knockouts in a Drosophila
      cell line for the first time. We have shown that homologous gene targeting is
      possible at 1-4% efficiency using this system, allowing for the construction of
      defined insertions and deletions. We demonstrate that a 1&emsp14;kb homology arm
      length is optimal for integration by homologous gene targeting, and demonstrate
      its efficacy by tagging the endogenous AGO1 protein. This technology enables
      controlled genetic manipulation in Drosophila cell lines, and its simplicity
      offers the opportunity to study cellular phenotypes genome-wide. 

PMID- 24326187
TI  - Gain-of-function mutations in the ALS8 causative gene VAPB have detrimental
      effects on neurons and muscles.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a motor neuron degenerative disease
      characterized by a progressive, and ultimately fatal, muscle paralysis. The human
      VAMP-Associated Protein B (hVAPB) is the causative gene of ALS type 8. Previous
      studies have shown that a loss-of-function mechanism is responsible for VAPB
      induced ALS. Recently, a novel mutation in hVAPB (V234I) has been identified but
      its pathogenic potential has not been assessed. We found that neuronal expression
      of the V234I mutant allele in Drosophila (DVAP-V260I) induces defects in synaptic
      structure and microtubule architecture that are opposite to those associated with
      DVAP mutants and transgenic expression of other ALS-linked alleles. Expression of
      DVAP-V260I also induces aggregate formation, reduced viability, wing postural
      defects, abnormal locomotion behavior, nuclear abnormalities, neurodegeneration
      and upregulation of the heat-shock-mediated stress response. Similar, albeit
      milder, phenotypes are associated with the overexpression of the wild-type
      protein. These data show that overexpressing the wild-type DVAP is sufficient to
      induce the disease and that DVAP-V260I is a pathogenic allele with increased wild
      type activity. We propose that a combination of gain- and loss-of-function
      mechanisms is responsible for VAPB-induced ALS. 

PMID- 24326188
TI  - Differential expression of the FMRF gene in adult and hatchling stellate ganglia
      of the squid Loligo pealei.
AB  - The giant fiber system of the squid Loligo pealei mediates the escape response
      and is an important neurobiological model. Here, we identified an abundant
      transcript in the stellate ganglion (SG) that encodes a FMRFamide precursor, and
      characterized FMRFamide and FI/LRF-amide peptides. To determine whether FMRFamide
      plays a role in the adult and hatchling giant fiber system, we studied the
      expression of the Fmrf gene and FMRFamide peptides. In stage 29 embryos and stage
      30 hatchlings, Ffmr transcripts and FMRFamide peptide were low to undetectable in
      the SG, in contrast to groups of neurons intensely expressing the Fmrf gene in
      several brain lobes, including those that innervate the SG. In the adult SG the
      Fmrf gene was highly expressed, but the FMRFamide peptide was in low abundance.
      Intense staining for FMRFamide in the adult SG was confined to microneurons and
      fibers in the neuropil and to small fibers surrounding giant axons in stellar
      nerves. This shows that the Fmrf gene in the SG is strongly regulated post
      hatching, and suggests that the FMRFamide precursor is incompletely processed in
      the adult SG. The data suggest that the SG only employs the Fmrf gene post
      hatching and restricts the biosynthesis of FMRFamide, demonstrating that this
      peptide is not a major transmitter of the giant fiber system. This contrasts with
      brain lobes that engage FMRFamide embryonically as a regulatory peptide in
      multiple neuronal systems, including the afferent fibers that innervate the SG.
      The biological significance of these mechanisms may be to generate diversity
      within Fmrf-expressing systems in cephalopods. 

PMID- 24326189
TI  - Sublethal mechanisms of Pb and Zn toxicity to the purple sea urchin
      (Strongylocentrotus purpuratus) during early development.
AB  - In order to understand sublethal mechanisms of lead (Pb) and zinc (Zn) toxicity,
      developing sea urchins were exposed continuously from 3h post-fertilization
      (eggs) to 96 h (pluteus larvae) to 55 (+/-2.4) MUgPb/L or 117 (+/-11)MUgZn/L,
      representing ~ 70% of the EC50 for normal 72 h development. Growth,
      unidirectional Ca uptake rates, whole body ion concentrations (Na, K, Ca, Mg),
      Ca(2+) ATPase activity, and metal bioaccumulation were monitored every 12h over
      this period. Pb exhibited marked bioaccumulation whereas Zn was well-regulated,
      and both metals had little effect on growth, measured as larval dry weight, or on
      Na, K, or Mg concentrations. Unidirectional Ca uptake rates (measured by (45)Ca
      incorporation) were severely inhibited by both metals, resulting in lower levels
      of whole body Ca accumulation. The greatest disruption occurred at gastrulation.
      Ca(2+) ATPase activity was also significantly inhibited by Zn but not by Pb.
      Interestingly, embryos exposed to Pb showed some capacity for recovery, as
      Ca(2+)ATPase activities increased, Ca uptake rates returned to normal
      intermittently, and whole body Ca levels were restored to control values by 72-96
      h of development. This did not occur with Zn exposure. Both Pb and Zn rendered
      their toxic effects through disruption of Ca homeostasis, though likely through
      different proximate mechanisms. We recommend studying the toxicity of these
      contaminants periodically throughout development as an effective way to detect
      sublethal effects, which may not be displayed at the traditional toxicity test
      endpoint of 72 h.

PMID- 24326190
TI  - PAH effects on meio- and microbial benthic communities strongly depend on
      bioavailability.
AB  - The effects of anthropogenic pollutants in dissimilar habitats can vary depending
      on differences in bioavailability. The factors determining bioavailability are
      not yet fully understood. This study was performed to evaluate whether analysis
      of total PAH concentrations in sediments is a satisfactory measurement to
      indicate environmental effects or if bioavailability is needed to be taken into
      account. We have here performed a 60-day experiment, where nominal PAH
      concentrations of 1,300 MUg/kg sediment were added to three different marine
      sediments. Meiofaunal and microbial communities were analyzed for alterations in
      community response at 30 and 60 days. Results showed that bioavailability of PAHs
      varied between the three different sediments. Nonetheless, the petroleum addition
      gave rise to significant negative effects on all three sediments at both time
      points. The two direct measurements of toxicity on the microbial community,
      potential nitrification and denitrification, displayed a lower effect of the PAH
      addition in the muddy sediment at both time points, compared to the other two
      sediment types. No effects were seen in the analysis of meiofaunal community
      structure. Measurements of PAH bioavailability in the three sediment types
      concurred with the results from the microbial community, revealing a lower
      bioavailability in the muddy sediment compared to the other two sediment types,
      34% compared to sandy and 18% compared to organic at day 0. At day 60 it was 61%
      lower compared to sandy and 20% lower compared to organic. The negative effects
      of the PAH addition on the microbial nitrogen cycle were in six out of eight
      cases best correlated to the amount of alkylated bioavailable PAH in the
      sediments, and thus microbial nitrogen cycle is a possible good indicator for
      assessing PAH-induced stress. The results presented here have implications for
      risk analysis studies of petroleum-contaminated marine sediments; consequently,
      sediment characteristics and its effects on bioavailability are important to
      include. In addition, these results add to the understanding that bioavailability
      measurements of PAHs are a more correct assessment compared to measurements of
      total PAH concentrations, and need to be included when estimating effects of PAHs
      in marine benthic communities.

PMID- 24326191
TI  - Expression, purification and improved antigenicity of the Mycobacterium
      tuberculosis PstS1 antigen for serodiagnosis.
AB  - The phosphate-specific transport substrate binding protein-1 (PstS1) is a
      potential antigen used for the serological diagnosis of tuberculosis. For a
      highly specific diagnostic result, it is important that the recombinant PstS1 be
      highly pure and correctly folded. In this study, the PstS1 was expressed as
      fusion protein with glutathione-S-transferase (PstS1-GST) and Escherichia coli
      trigger factor (PstS1-TF) and their immunodiagnostic potentials were evaluated.
      The insoluble PstS1-GST was denatured and refolded to the native conformation by
      a step-gradient dilution, followed by purification with affinity chromatography
      on immobilized glutathione whereas the soluble PstS1-TF was directly purified by
      Ni-NTA affinity and size-exclusion chromatographies. The levels of antibody
      responses to PstS1-TF and PstS1-GST were measured by enzyme-linked immunosorbent
      assay (ELISA) in the sera of 22 tuberculosis patients with smear-positive and
      culture-positive tuberculosis as well as 20 healthy individuals; the
      antigenicities of the samples were evaluated in terms of sensitivity and
      specificity. To determine the diagnostic accuracy, receiver operation
      characteristic (ROC) curves were constructed and then the areas under the ROC
      curves (AUC) were calculated; the AUC values for PstS1-TF and PstS1-GST were
      0.971 and 0.877 with 95% confidence intervals (CI) of 0.927-1.000 and 0.768
      0.986, respectively. The specificity of PstS1-TF was reduced from 89.5% to 84.2%,
      but in case of PstS1-GST it dropped drastically from 78.9% to 26.3% when the
      sensitivity was raised from 86.4% up to 95.5%. These results indicate that PstS1
      TF is capable of producing more accurate and consistent serodiagnostic results
      than PstS1-GST, possibly due to its conformation being closer to the native
      state. 

PMID- 24326192
TI  - Use of IPTG-inducible promoters for anchoring recombinant proteins on the
      Bacillus subtilis spore surface.
AB  - The method of surface display allows the fusion of passenger proteins to a
      carrier protein displayed on the outside of bioparticles such as spores. Here, we
      used spores of Bacillus subtilis, the outer surface proteins CotB, CotC, and CotG
      as carrier and the amyQ-encoded alpha-amylase and GFPuv as passenger proteins.
      The different translational fusions were fused to two different IPTG-inducible
      promoters, and the regulated expression level of both passenger proteins were
      measured in relation to the inducer concentration added to sporulating cells. It
      turned out that the amount of fusion protein on the outside of spores was
      dependent on the amount of IPTG added, but the optimal amount of inducer varied
      depending on the carrier and the passenger proteins. These experiments
      demonstrate that a regulatable expression of passenger proteins on the surface of
      spores is possible. This will help to adjust the amount of any passenger protein
      to that needed for specific purposes. 

PMID- 24326194
TI  - Orbital myositis in Behcet's disease.

PMID- 24326193
TI  - Improved purification and enzymatic properties of a mixture of Sticholysin I and
      II: isotoxins with hemolytic and phospholipase A(2) activities from the sea
      anemone Stichodactyla helianthus.
AB  - Sticholysin I and Sticholysin II (StI and StII) are two potent hemolysins which
      form pores in natural and model membranes at nanomolar concentrations. These
      proteins were purified from the aqueous extract of the sea anemone Stichodactyla
      helianthus, Ellis 1768, by gel filtration and ionic exchange chromatography. This
      procedure rendered StI and StII with high purity (purification factors: 36 and
      50, respectively) but a low yield of hemolytic activity, HA (<3%). Additionally,
      these toxins exhibited very low phospholipase activity (10(-3)U/mg of protein).
      In this work, a mixture StI-StII was obtained (yield >95%, with an increase in
      specific activity: 14 times) from the animal extract using an oxidized
      phospholipid-based affinity chromatographic matrix binding phospholipases.
      Cytolysin identification in the mixture was performed by immunoblotting and N
      terminal sequence analyses. Phospholipase A2 (PLA2) activity of StI-StII was
      relatively high (1.85U/mg) and dependent of Ca(2+). The activity resulted optimum
      when was measured with the mostly unsaturated soybean phosphatidylcholine (PC),
      when compared to the less unsaturated egg PC or completely saturated dipalmitoyl
      PC, in the presence of 40mM Ca(2+) at pH 8.0. This Ca(2+) concentration did not
      exert any effect on binding of StI-StII with soybean PC monolayers. Then, PLA2
      activity seems not be required to binding to membranes. 

PMID- 24326195
TI  - Factors influencing return to work after illness in France.
AB  - BACKGROUND: Few studies have been published about the factors influencing return
      to work after sickness absence. AIMS: To identify medical and occupational
      factors influencing the type of fitness certificate given by occupational
      physicians before employees return to work after sickness absence. METHODS: A
      cross-sectional study was undertaken over 3 months in several health services in
      France. Workers undergoing a medical examination before returning to work after a
      period of sickness absence of at least 3 weeks were included. Medical and
      occupational factors were collected using a questionnaire. The relationship
      between different factors and certification of fitness was assessed by univariate
      and multivariate analyses. RESULTS: Among the 402 workers included, 64% were
      considered fit to return to work. Being older, strenuous work, prolonged sick
      leave and fear of returning to work appeared to be negative factors influencing
      the return to a previous job. In contrast, having an education level higher than
      secondary school, being satisfied at work, perception of very good health and
      benefitting from satisfactory professional relationships appeared to favour
      return to work. We developed a predictive score of not being fit to return to
      work after illness. CONCLUSIONS: Our study highlighted the relationship between
      medical and occupational factors with problems returning to work. The predictive
      score may be used by occupational physicians as a screening tool to identify
      those who are likely to have difficulties returning to work after illness, so
      that their working conditions can be modified to take this into consideration.

PMID- 24326196
TI  - Accuracy of body mass index in volunteer firefighters.
AB  - BACKGROUND: Obesity is prevalent among career firefighters and may contribute to
      heart attacks, a leading cause of on-duty fatalities. The US National Fire
      Protection Association estimates that 800 000 of 1.1 million firefighters are
      volunteers. Body mass index (BMI) is commonly used to assess obesity, but little
      is known about its accuracy in volunteer firefighters, in whom muscle mass may be
      higher, given firefighting's physical demands, reducing its accuracy in
      identifying obesity. AIMS: To evaluate the accuracy of BMI in identifying obese
      volunteer firefighters. METHODS: Height, weight and body composition were
      measured in 73 male volunteer firefighters (mean age 40+/-12). The proportions
      with BMI >= 25kg/m(2), >=30kg/ m(2) and percent fat <= 20th percentile were
      determined. Using the age-specific 20th percentile for percent fat (Cooper
      Clinic) as the criterion for being over-fat, the accuracy of BMI was assessed
      using sensitivity and specificity calculations. RESULTS: The means +/- standard
      deviation of BMI and percent fat were 32+/-6 and 25+/-5, respectively. The
      proportions with a BMI >= 25 and >=30 were 90% and 60%, respectively. Fifty-one
      percent had a percent fat <= 20th percentile. The measure BMI >= 25 had a perfect
      sensitivity (1.0) and low specificity (0.19) and BMI >= 30 had a high sensitivity
      (0.89) and moderate specificity (0.69). CONCLUSIONS: Although BMI >= 30
      accurately predicted being over-fat, it misclassified large and lean
      firefighters. Although BMI should be used cautiously, it can identify over-fat
      firefighters at risk of cardiovascular disease, and its measurement is cost
      effective and simple.

PMID- 24326197
TI  - Differential resting-state EEG patterns associated with comorbid depression in
      Internet addiction.
AB  - OBJECTIVE: Many researchers have reported a relationship between Internet
      addiction and depression. In the present study, we compared the resting-state
      quantitative electroencephalography (QEEG) activity of treatment-seeking patients
      with comorbid Internet addiction and depression with those of treatment-seeking
      patients with Internet addiction without depression, and healthy controls to
      investigate the neurobiological markers that differentiate pure Internet
      addiction from Internet addiction with comorbid depression. METHOD: Thirty-five
      patients diagnosed with Internet addiction and 34 age-, sex-, and IQ-matched
      healthy controls were enrolled in this study. Patients with Internet addiction
      were divided into two groups according to the presence (N=18) or absence (N=17)
      of depression. Resting-state, eye-closed QEEG was recorded, and the absolute and
      relative power of the brain were analyzed. RESULTS: The Internet addiction group
      without depression had decreased absolute delta and beta powers in all brain
      regions, whereas the Internet addiction group with depression had increased
      relative theta and decreased relative alpha power in all regions. These
      neurophysiological changes were not related to clinical variables. CONCLUSION:
      The current findings reflect differential resting-state QEEG patterns between
      both groups of participants with Internet addiction and healthy controls and also
      suggest that decreased absolute delta and beta powers are neurobiological markers
      of Internet addiction.

PMID- 24326198
TI  - Photobiomodulation accelerates orthodontic alignment in the early phase of
      treatment.
AB  - BACKGROUND: Numerous strategies have been proposed to decrease the treatment time
      a patient requires in orthodontic treatment. Recently, a number of device
      accelerated therapies have emerged in orthodontics. Photobiomodulation is an
      emerging area of science that has clinical applications in a number of human
      biological processes. The aim of this study was to determine if
      photobiomodulation reduces the treatment time in the alignment phase of
      orthodontic treatment. METHODS: This multicenter clinical trial was performed on
      90 subjects (73 test subjects and 17 controls), and Little's Index of
      Irregularity (LII) was used as a measure of the rate of change of tooth movement.
      Subjects requiring orthodontic treatment were recruited into the study, and the
      LII was measured at regular time intervals. Test subjects used a device which
      produced near-infrared light with a continuous 850-nm wavelength. The surface of
      the cheek was irradiated with a power density of 60 mW/cm2 for 20 or 30 min/day
      or 60 min/week to achieve total energy densities of 72, 108, or 216 J/cm2,
      respectively. All subjects were fitted with traditional orthodontic brackets and
      wires. The wire sequences for each site were standardized to an initial round
      alignment wire (014 NiTi or 016 NiTi) and then advanced through a progression of
      stiffer arch wires unit alignment occurred (LII<1 mm). RESULTS: The mean LII
      scores at the start of the clinical trial for the test and control groups were
      6.35 and 5.04 mm, respectively. Multi-level mixed effect regression analysis was
      performed on the data, and the mean rate of change in LII was 0.49 and 1.12
      mm/week for the control and test groups, respectively. CONCLUSIONS:
      Photobiomodulation produced clinically significant changes in the rates of tooth
      movement as compared to the control group during the alignment phase of
      orthodontic treatment.

PMID- 24326199
TI  - Sustained high serum malondialdehyde levels are associated with severity and
      mortality in septic patients.
AB  - INTRODUCTION: There is a hyperoxidative state in sepsis. The objective of this
      study was to determine serum malondialdehyde (MDA) levels during the first week
      of follow up, whether such levels are associated with severity during the first
      week and whether non-surviving patients showed higher MDA levels than survivors
      during the first week. METHODS: We performed an observational, prospective,
      multicenter study in six Spanish Intensive Care Units. Serum levels of MDA were
      measured in 328 patients (215 survivors and 113 non-survivors) with severe sepsis
      at days one, four and eight of diagnosis, and in 100 healthy controls. The
      primary endpoint was 30-day mortality and the secondary endpoint was six -month
      mortality. The association between continuous variables was carried out using
      Spearman's rank correlation coefficient. Cox regression analysis was applied to
      determine the independent contribution of serum MDA levels on the prediction of
      30-day and 6-month mortality. Hazard ratio (HR) and 95% confidence intervals (CI)
      were calculated as measures of the clinical impact of the predictor variables.
      RESULTS: We found higher serum MDA in septic patients at day one (p < 0.001), day
      four (p < 0.001) and day eight (p < 0.001) of diagnosis than in healthy controls.
      Serum MDA was lower in surviving than non-surviving septic patients at day one (p
      < 0.001), day four (p < 0.001) and day eight (p < 0.001). Serum MDA levels were
      positively correlated with lactic acid and SOFA during the first week. Finally,
      serum MDA levels were associated with 30-day mortality (HR = 1.05; 95% CI = 1.02
      1.09; p = 0.005) and six-month mortality (hazard ratio (HR) = 1.05; 95% CI = 1.02
      1.09; p = 0.003) after controlling for lactic acid levels, acute physiology and
      chronic health evaluation (APACHE)-II, diabetes mellitus, bloodstream infection
      and chronic renal failure. CONCLUSIONS: To our knowledge, this is the largest
      series providing data on the oxidative state in septic patients to date. The
      novel finding is that high serum MDA levels sustained throughout the first week
      of follow up were associated with severity and mortality in septic patients.

PMID- 24326200
TI  - Autonomic dysfunction in different subtypes of post-acute ischemic stroke.
AB  - OBJECTIVES: Central autonomic impairment is frequent in ischemic stroke at acute
      or chronic stages. The mechanism by which these symptoms occur in patients with
      ischemic stroke has not been elucidated. This study sought to investigate
      cardiovascular autonomic function in patients with different subtypes of post
      acute ischemic stroke. METHODS: 77 ischemic stroke patients [50 patients with
      large-artery atherosclerosis (LAA) and 27 patients with small-vessel occlusion
      (SVO), average 6 months after stroke onset] and 37 elderly controls were
      recruited. All performed Ewing's battery autonomic function tests and power
      spectral analysis of heart rate variability (HRV). RESULTS: Stroke patients with
      both LAA and SVO had significantly lower low frequency power spectral density
      than controls. The prevalence of autonomic dysfunction in both groups (82.0%
      patients with LAA and 63.0% with SVO) was higher than that in controls (21.6%).
      Patients with LAA showed impairment of all parasympathetic tests (all P<0.05) and
      one of the sympathetic tests (mean fall in systolic blood pressure on standing: P
      = 0.058) and those with SVO only showed impairment in two parasympathetic tests
      (heart rate response to deep breathing: P = 0.010; heart rate response to
      standing: P = 0.004) in comparison with controls. Patients with LAA had
      significantly more impairment than those with SVO in some autonomic parameters
      (Valsalva ratio: P = 0.039; mean fall in systolic blood pressure on standing: P =
      0.015). CONCLUSIONS: Irrespective of the subtype of the ischemia, post-acute
      stroke patients showed a parasympathetic cardiac deficit. Additionally,
      parasympathetic and sympathetic cardiovascular modulations were more severely
      impaired in patients with LAA.

PMID- 24326201
TI  - Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease.
AB  - SNCA is a pathogenic gene identified in rare familial PD, and over-expression of
      SNCA was suggested in the pathogenesis of familial and sporadic PD. Rep1
      polymorphism of SNCA was associated with susceptibility to sporadic PD and SNCA
      expression in intro and in vivo. Hypomethylation in SNCA intron-1 was associated
      with increased SNCA expression and was observed in postmortem brains of patients
      with sporadic PD. We studied the methylation status of SNCA intron-1, SNCA mRNA
      levels and Rep1 genotypes in PBMCs of 100 sporadic PD patients and 95 controls
      and explored the relationship between DNA methylation, mRNA expression and Rep1
      genotypes. Hypomethylation of SNCA intron-1 was detected in PBMCs of PD patients,
      and DNA methylation levels were associated with Rep1 polymorphism. The shorter
      allele was associated with higher level of SNCA intron-1 methylation, and
      genotypes carrying the shorter allele showed significantly higher methylation
      level of SNCA intron-1 than genotypes carrying the longer allele. However, SNCA
      mRNA levels were not associated with disease status, Rep1 polymorphism or DNA
      methylation of SNCA intron-1 in our study. 

PMID- 24326202
TI  - Investigations of single nucleotide polymorphisms in folate pathway genes in
      Chinese families with neural tube defects.
AB  - AIMS: We investigated the hypothesis that there are interactions between SNPs in
      folate metabolism pathway genes and environmental risk factors to the etiology of
      neural tube defects (NTDs). METHOD: In 602 Chinese families, 609 aborted fetus
      tissues or blood samples were collected from NTD individuals, and 1106 parental
      blood samples were detected as controls. We analyzed 28 SNPs in 12 folate pathway
      genes. Folate supplementation, gestational diabetes mellitus (GDM) and medicine
      administration before and during pregnancy were investigated. Case-parental
      control study and transmission/disequilibrium tests were performed according to
      environmental cofactor stratification. RESULTS: Association between 5,10
      methylenetetrahydrofolate reductase (MTHFR) 677C>T and NTDs was significant in
      all stratifications (all P<.05), and synergistic effects of no folate
      supplementation and GDM were shown on NTD occurrence. 5-Methyltetrahydrofolate
      homocysteine methyltransferase (MTHM) 501A>G in case of GDM, and betaine
      homocysteine methyltransferase (BHMT) 716G>A in case of no folate supplementation
      significantly associated with NTDs (both P<.05), whereas the two genotypes alone
      did not significantly associate with NTDs (both P>.05). CONCLUSIONS: MTHFR 677C>T
      genotype, especially in case of no folate supplementation and GDM, promotes NTD
      occurrence. MTHM 501A>G only in case of GDM, and BHMT 716G>A only in case of no
      folate supplementation contribute to the etiology of NTDs.

PMID- 24326204
TI  - "King hit" fatalities in Australia, 2000-2012: the role of alcohol and other
      drugs.
AB  - INTRODUCTION: "King hits" are when a single blow to the head causes a victim to
      fall to the ground unconscious, either from the punch itself or the impact
      between the head and the ground. This can result in fatal skull fractures and
      subdural hematomas. This study aimed to establish the prevalence of king hit
      deaths in Australia and determine the involvement of drugs in these violent
      fatalities. METHODS: The National Coronial Information System was used to
      retrieve all cases involving a king hit within Australia between 2000 and 2012.
      RESULTS: 90 cases were identified with a median age of 33 years (range 15-78).
      There were 4 females. Most cases occurred in the state of New South Wales (n=28),
      followed by Victoria and Queensland (24 cases each), at a hotel or pub before
      3a.m. Toxicology reports were available in 68 cases. Of these, 53 cases involved
      the use of alcohol or other drugs (other than those used in hospital treatment).
      Forty-nine cases (73%) involved the use of alcohol, with a median alcohol
      concentration of 0.144g/100mL and 0.191g/100mL in ante-mortem and post-mortem
      specimens, respectively. Illicit drugs were detected in 10 cases of which most
      involved cannabis. Other pharmaceutical drugs were detected in 3 cases.
      DISCUSSION: Assaults are an ongoing problem in Australia and king hits form a
      large group of these substance-related and often unprovoked attacks. Importantly,
      this study indicated that alcohol intoxication increases the risk of
      victimization, not just aggressive offending. This reiterates the serious
      consequences of alcohol-fueled violence in Australia.

PMID- 24326203
TI  - Neighborhood-level LGBT hate crimes and current illicit drug use among sexual
      minority youth.
AB  - OBJECTIVE: To investigate whether past-30 day illicit drug use among sexual
      minority youth was more common in neighborhoods with a greater prevalence of hate
      crimes targeting lesbian, gay, bisexual, and transgender (LGBT, or sexual
      minority) individuals. METHODS: We used a population-based survey of public
      school youth in Boston, Massachusetts, consisting of 1292 9th-12th grade students
      from the 2008 Boston Youth Survey Geospatial Dataset (sexual minority n=108).
      Data on LGBT hate crimes involving assaults or assaults and battery between 2005
      and 2008 were obtained from the Boston Police Department and linked to youths'
      residential address. Youth reported past-30 day use of marijuana and other
      illicit drugs. Wilcoxon-Mann-Whitney tests and corresponding p-values were
      computed to assess differences in substance use by neighborhood-level LGBT
      assault hate crime rate among sexual minority youth (n=103). RESULTS: The LGBT
      assault hate crime rate in the neighborhoods of sexual minority youth who
      reported current marijuana use was 23.7 per 100,000, compared to 12.9 per 100,000
      for sexual minority youth who reported no marijuana use (p=0.04). No associations
      between LGBT assault hate crimes and marijuana use among heterosexual youth
      (p>0.05) or between sexual minority marijuana use and overall neighborhood-level
      violent and property crimes (p>0.05) were detected, providing evidence for result
      specificity. CONCLUSIONS: We found a significantly greater prevalence of
      marijuana use among sexual minority youth in neighborhoods with a higher
      prevalence of LGBT assault hate crimes. These results suggest that neighborhood
      context (i.e., LGBT hate crimes) may contribute to sexual orientation disparities
      in marijuana use.

PMID- 24326205
TI  - Associations of pulse pressure index with left ventricular filling pressure and
      diastolic dysfunction in patients with chronic kidney disease.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) often have poor vascular
      compliance and poor left ventricular diastolic dysfunction (LVDD). The pulse
      pressure index (PPI) defined as ((systolic blood pressure - diastolic blood
      pressure)/systolic blood pressure) reflects vascular compliance. Vascular
      compliance is reportedly associated with left ventricular diastolic function.
      This study of CKD patients investigated whether PPI correlates with the ratio of
      transmitral E wave velocity (E) to early diastole mitral annulus velocity (Ea) or
      with LVDD. METHODS: This study enrolled 511 CKD patients who had been referred
      for echocardiographic examination. Blood pressure was automatically measured with
      an ABI-form device. The LVDD was defined as E-to-transmitral A wave velocity
      ratio of >=0.9, Ea <8 cm/s, or E/Ea >=15. RESULTS: Compared with those with E/Ea
      <15, patients with E/Ea >=15 had significantly higher systolic blood pressure,
      pulse pressure, and PPI (all P < 0.001). Multivariable analysis showed that PPI
      was independently associated with E/Ea (unstandardized coefficient beta = 1.348;
      P < 0.001) and with LVDD (odds ratio = 1.441 per 0.064 increase; P < 0.001).
      CONCLUSIONS: This study showed that increased PPI significantly correlates with
      elevated E/Ea and LVDD in CKD patients. Because PPI can be rapidly acquired
      during blood pressure measurement, it may be helpful for identifying CKD patients
      with a high left ventricular filling pressure and LVDD.

PMID- 24326206
TI  - Up-regulated death-associated LIM-only protein contributes to fitness costs of
      Bacillus thuringiensis Cry1Ac resistance in Helicoverpa armigera.
AB  - The evolution of Bacillus thuringiensis (Bt) resistance provides a useful pathway
      for the study of fitness trade-offs associated with stress adaptation. In a
      previous study, we used cDNA-amplification fragment length polymorphism (cDNA
      ALFP) analysis to identify differentially expressed genes (DEGs) in Cry1Ac
      susceptible (96S) and -resistant (Bt-R) Helicoverpa armigera larvae. Among these
      DEGs, a death-associated LIM-only protein (HaDALP) was identified. In the current
      study, the full-length cDNA encoding HaDALP was cloned using rapid amplification
      of cDNA ends according to an expressed sequence tag derived from the previous
      cDNA-ALFP analysis. HaDALP expression patterns indicated that this gene was
      differentially expressed in tissues and stages and was highest in the midgut and
      epidermis of the 5th instar larvae. It is up-regulated in Cry1Ac-resistant H.
      armigera larvae. Fitness parameters, such as larval and pupal weight, pupal
      duration, and survival rate, which are the most sensitive indicators, were
      evaluated after HaDALP knockdown or feeding of the HaDALP protein in vivo. Our
      findings suggested that up-regulation of HaDALP might be related to Cry1Ac
      resistance and an adaption to Bt toxins. 

PMID- 24326207
TI  - Bronchopleural fistula after non small cell lung cancer radiofrequency ablation:
      what it implying to us?
AB  - Radiofrequency ablation (RFA) is an alternative method to treat the inoperable
      NSCLC and there were few serious complications after RFA therapy have been
      reported. Here, we reported a NSCLC patient endured empyema after treatment by
      RFA for one month. There was a 20 * 25 * 20 mm mass on the right middle lobe by
      CT scan before RFA and a huge gas cavity with liquid was found in the right chest
      cavity after RFA treatment for twenty- eight days. A hole in the right middle
      lobe was found with large amount of pus in the pleural cavity as well as the
      bronchopleural fistula (BPF) during the operation. Results from the postoperative
      pathology showed a multiple small foci differentiated adenocarcinoma, partial
      bronchiolar-alveolar carcinoma, 0.5 cm away around the hole at the same time. It
      is difficult to diagnose and treat the rare complication of BPF, while, the
      larger field of ablation might be helpful to postpone the tumor local
      progression. Therefore, surgery was a good option for BPF especially when an
      empyema occurred. Virtual slides: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/8028049341122276.

PMID- 24326208
TI  - Congenital left atrial bands and cardioembolic events.

PMID- 24326209
TI  - Serum sRANKL/OPG predict recurrence after radiofrequency catheter ablation of
      lone atrial fibrillation.
AB  - BACKGROUND: Radiofrequency catheter ablation (RFCA) is a widely accepted strategy
      for eliminating atrial fibrillation (AF). A considerable recurrence rate has
      partly been ascribed to atrial remodeling. Osteoprotegerin (OPG)/receptor
      activator of nuclear factor-kappaB (RANK)/RANK ligand (RANKL) axis may contribute
      to the development and progression of AF by regulating atrial structural
      remodeling. This study aimed to determine the relationship between serum soluble
      RANKL (sRANKL)/OPG and the risk of recurrent arrhythmia after ablation of lone
      AF. METHODS: We enrolled 527 lone AF patients undergoing first-time RFCA with
      complete follow-up data. Pre-ablation venous blood samples were obtained for
      measurement of serum sRANKL and OPG. RESULTS: During the follow-up period of 15
      (3-64)months, AF recurred in 187 patients (35.5%). Recurrence was associated with
      an elevation of serum sRANKL level and sRANKL/OPG ratio. In multivariate survival
      regression, persistent AF, AF duration, left atrial diameter, amiodarone after
      ablation, particularly serum sRANKL level and sRANKL/OPG ratio independently
      predicted AF recurrence. According to ROC curve analysis, the best diagnostic
      values of serum sRANKL level and sRANKL/OPG ratio for predicting recurrence were
      4.89 pmol/l and 0.76, respectively. CONCLUSIONS: Baseline serum high sRANKL level
      and sRANKL/OPG ratio are associated with AF recurrence after primary ablation
      procedure in lone AF patients, and may be used in the prediction of AF recurrence
      in these patients.

PMID- 24326210
TI  - Exercise training program characteristics and magnitude of change in functional
      capacity of heart failure patients.
AB  - BACKGROUND: Intuitively higher exercise program volume may be the primary
      stimulus for physical adaptation. We sought to establish if aerobic exercise
      training program characteristics produced different effect sizes for change in
      cardiorespiratory fitness in heart failure patients. METHODS: We conducted a
      MEDLINE search (1966 to 2012), for exercise based rehabilitation trials in heart
      failure, using the search terms 'exercise training, left ventricular dysfunction,
      peak VO2, cardio-myopathy and systolic heart dysfunction'. Forty seven studies
      were included, producing 54 intervention groups; 3 (6%) were high-, 29 (54%)
      vigorous-, 20 (37%) moderate- and 2 (3%) low- intensity groups, providing a total
      of 2285 exercising subjects and 2098 control subjects, totaling 4383
      participants. RESULTS: Peak VO2 increased by a mean difference of 3.3 ml kg(
      1)min(-1) [95% CI 0.53 to 6.13, p=0.02] with high intensity training in exercise
      groups versus control, equating to a 23% improvement from baseline. The
      corresponding data for vigorous, moderate and low intensity were 8%, 13%; and 7%
      respectively. Weekly exercise energy expenditure >460 kcal was associated with a
      mean difference in peak VO2 of 2.6 ml kg(-1)min(-1) [95% CI 1.88 to 3.28,
      p<0.00001]. CONCLUSIONS: Our data suggest that high-intensity exercise, achieving
      at least 460 kcal weekly energy expenditure may elicit the greatest changes in
      cardiorespiratory fitness.

PMID- 24326211
TI  - Flocculation of high purity wheat straw soda lignin.
AB  - In industrial process, acidification causes non-sulfonated lignin insolubility.
      The flocculants poly(diallyldimethylammonium chloride) (pDADMAC) and bovine blood
      (BB) also caused lignin insolubility while cationic polyacrylamide, chitosan, and
      soy protein PF 974 were ineffective. Turbidity determined optimal flocculant, but
      turbidity magnitude with BB was greater than expected. pDADMAC caused negative
      lignin Zeta potential to became positive, but BB-lignin Zeta potential was always
      negative. Insoluble lignin did not gravity sediment, and flocculant-lignin
      mixtures were centrifuged. Pellet and supernatant dry mass and corrected
      spectroscopic results were in good agreement for optimal pDADMAC and BB.
      Spectroscopy showed 87-92% loss of supernatant lignin. Nitrogen analysis showed
      BB concentrated in the pellet until the pellet became saturated with BB.
      Subtracting ash and BB mass from pellet and supernatant mass confirmed optimal
      BB. Low levels of alum caused increased lignin flocculation at lower levels of
      pDADMAC and BB, but alum did not affect optimal flocculant. 

PMID- 24326212
TI  - Aerobic granulation of aggregating consortium X9 isolated from aerobic granules
      and role of cyclic di-GMP.
AB  - This study monitored the granulation process of an aggregating functional
      consortium X9 that was consisted of Pseudomonas putida X-1, Acinetobacter sp. X
      2, Alcaligenes sp. X-3 and Comamonas testosteroni X-4 in shaken reactors. The
      growth curve of X9 was fit using logistic model as follows y=1.49/(1+21.3*exp(
      0.33x)), the maximum specific cell growth rate for X9 was 0.33 h(-1). Initially
      X9 consumed polysaccharides (PS) and secreted proteins (PN) to trigger
      granulation. Then X9 grew in biomass and formed numerous micro-granules, driven
      by increasing hydrophobicity of cell membranes and of accumulated extracellular
      polymeric substances (EPS). In later stage the intracellular cyclic diguanylate
      (c-di-GMP) was at high levels for inhibiting bacteria swarming motility, thereby
      promotion formation of large aerobic granules. The findings reported herein
      advise the way to accelerate granule formation and to stabilize operation in
      aerobic granular reactors.

PMID- 24326213
TI  - Extraction decision and identification of treatment predictors in Class I
      malocclusions.
AB  - BACKGROUND: The extraction rate in orthodontics varies throughout the years.
      While the extraction decision is easily made or excluded in clear-cut cases, it
      still remains controversial what makes an orthodontist decide to extract in
      borderline cases. The aim of this retrospective study was to identify the
      percentage of extraction cases in a large group of Class I malocclusions and to
      clarify which variables contributed most to the extraction decision. METHODS: The
      sample consisted of 542 randomly selected records of Class I patients treated in
      a university graduate program and in five private orthodontic offices. Of these
      patients, 331 were female and 211 male. The mean age was 14.55 (standard
      deviation (SD) 5.36) for the non-extraction group and 14.52 (SD 4.86) for the
      extraction group. The extensive series of 32 linear and angular measurements
      derived from the cephalometric analysis and the dental casts, along with the
      variables of age and gender, fueled a stepwise discriminant analysis. RESULTS:
      The percentage of the patients treated with four first premolar extractions was
      26.8%. The results showed that the variables of lower crowding, lower lip to E
      plane, upper crowding, and overjet accounted most for the decision to extract at
      a very significant level (Sig. 0.000). The discriminant analysis assigned a
      classification power of 83.9% to the predictive model (p<0.0001). Fisher's linear
      discriminant functions provided a mathematical model, according to which any case
      can be classified into the adequate treatment group. CONCLUSIONS: In a large
      contemporary sample of 542 Class I patients, the extraction rate was 26.8%. The
      most important measurements when the orthodontist decides extractions in Class I
      cases are lower crowding, lower lip to E-plane, upper crowding, and overjet. In
      clinical orthodontic practice, the findings facilitate treatment by providing
      evidence-based treatment predictors for Class I malocclusions.

PMID- 24326214
TI  - Steps toward validity in active living research: research design that limits
      accusations of physical determinism.
AB  - "Active living research" has been accused of being overly "physically
      deterministic" and this article argues that urban planners must continue to
      evolve research and address biases in this area. The article first provides
      background on how researchers have dealt with the relationship between the built
      environment and health over years. This leads to a presentation of how active
      living research might be described as overly deterministic. The article then
      offers lessons for researchers planning to embark in active-living studies as to
      how they might increase validity and minimize criticism of physical determinism. 

PMID- 24326215
TI  - Nodular pericardial metastases.

PMID- 24326216
TI  - Iterative reconstruction of cryo-electron tomograms using nonuniform fast Fourier
      transforms.
AB  - Algorithms for three-dimensional (3D) reconstruction of objects based on their
      projections are essential in various biological and medical imaging modalities.
      In cryo-electron tomography (CET) a major challenge for reconstruction is the
      limited range of projection angles, which manifests itself as a "missing wedge"
      of data in Fourier space making the reconstruction problem ill-posed. Here, we
      apply an iterative reconstruction method that makes use of nonuniform fast
      Fourier transform (NUFFT) to the reconstruction of cryo-electron tomograms.
      According to several measures the reconstructions are superior to those obtained
      using conventional methods, most notably weighted backprojection. Most
      importantly, we show that it is possible to fill in partially the unsampled
      region in Fourier space with meaningful information without making assumptions
      about the data or applying prior knowledge. As a consequence, particles of known
      structure can be localized with higher confidence in cryotomograms and
      subtomogram averaging yields higher resolution densities. 

PMID- 24326217
TI  - Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of
      death. A nationwide registry-based cohort study.
AB  - BACKGROUND & AIMS: Population-based studies of the clinical course of autoimmune
      hepatitis are scarce. We conducted a nationwide study of incidence, prevalence,
      prognosis, and causes of death of autoimmune hepatitis in Denmark. METHODS: From
      nationwide healthcare registries we identified all Danish citizens diagnosed with
      autoimmune hepatitis in 1994-2012 and their liver biopsy data. We followed
      patients through January 2013 and examined age-standardized incidence and
      prevalence, mortality, prognostic factors, risk of hepatocellular carcinoma, and
      causes of death. We used Cox regression to compare patients' mortality relative
      to a gender- and age-matched general population sample. RESULTS: We included 1721
      autoimmune hepatitis patients. The incidence rate was 1.68 (95% confidence
      interval 1.60 to 1.76) per 100,000 population per year, and it doubled during the
      study period. Of the 1318 patients who were biopsied at diagnosis, 28.3% had
      cirrhosis. The 10-year cumulative risk of hepatocellular carcinoma was 0.7% (95%
      confidence interval 0.3 to 1.5). Male gender and cirrhosis were associated with
      high mortality and development of hepatocellular carcinoma. In the first year
      after diagnosis, patients with autoimmune hepatitis had six-fold higher mortality
      than the general population; later, their mortality remained two-fold higher.
      Their 10-year cumulative mortality was 26.4% (95% confidence interval 23.7 to
      29.1). 38.6% of deaths were liver-related including 3.6% from hepatocellular
      carcinoma. CONCLUSIONS: This nationwide population-based study of autoimmune
      hepatitis showed that the incidence increased during 1994-2012, and that the
      disease remains associated with a high mortality, particularly in the first year
      after diagnosis. Male gender and cirrhosis were adverse prognostic factors.

PMID- 24326218
TI  - Growing up with cancer: accommodating the effects of cancer into young people's
      social lives.
AB  - Adolescence and young adulthood are transitional periods of rapid and dramatic
      personal change. Few events can cause as unpredictable and challenging
      alterations to this process as the onset of a serious illness, such as cancer.
      Although we know much about the physical and psychological consequences of having
      cancer at this time, we know little about the effect of cancer on young people's
      relationships. We conducted interviews with 15 women and 12 men aged between 16
      and 29 years, who had survived cancer. Our findings demonstrate that the
      experience of cancer and how it affects relationships is complex. It arrests
      young people's development by increasing their dependence on parents, giving them
      life experiences unavailable to peers, and complicating the process of
      establishing new relationships. However, it also accelerates development by
      facilitating closer and more mature relationships with parents and giving young
      people wisdom and insight not shared by peers. Cancer profoundly shapes how young
      people conduct their relationships. These changes require ongoing accommodation
      by young people with cancer, their parents, peers, and new acquaintances. 

PMID- 24326219
TI  - Impact of social support on bereaved siblings' anxiety: a nationwide follow-up.
AB  - PURPOSE: To assess adolescent and young adult siblings' perception of social
      support prior to and following the loss of their brother or sister to cancer, 2
      to 9 years earlier, and their anxiety at follow-up. METHOD: In 2009, 174 (73%)
      bereaved siblings (12-25 years) participated in a nationwide, long-term follow-up
      study in Sweden using an anonymous study-specific questionnaire. The Hospital
      Anxiety and Depression Scale was used to measure self-assessed anxiety. RESULTS:
      Siblings had a higher risk of anxiety if they perceived their need for social
      support was unsatisfied during their brother or sisters' last month before death,
      relative risk (RR) = 3.6 (95% confidence interval [CI] = 1.8-7.3); time after
      death, RR = 2.9 (95% CI = 1.5-5.6); and at follow-up, RR = 3.8 (95% CI = 2.0
      7.2). Furthermore, a higher risk for anxiety was shown for siblings if they did
      not perceive that their parents and neighbors cared for them after their brother
      or sisters' death, RR = 2.7 (95% CI = 1.3-5.5), RR = 5.4 (95% CI = 1.3-21.9),
      respectively. CONCLUSION: Bereaved siblings had a greater probability to report
      self-assessed anxiety if they perceived that their need for social support was
      not satisfied prior to and following death. Information from both nurses and
      other health care professionals to families about the impact of social support
      may contribute to lessen the siblings' risk of anxiety.

PMID- 24326220
TI  - Ultrasound-assisted oxidation of dibenzothiophene with phosphotungstic acid
      supported on activated carbon.
AB  - Phosphotungstic acid (HPW) supported on activated carbon (AC) was applied to
      catalyze deep oxidation desulfurization of fuel oil with the assist of
      ultrasound. The sulfur-conversion rate was evaluated by measuring the
      concentration of dibenzothiophene (DBT) in n-octane before and after the
      oxidation. Supporting HPW on AC has been verified to play a positive role in UAOD
      process by a series of contrast tests, where only HPW, AC or a mixture of free
      HPW and AC was used. The influences of catalyst dose, ultrasound power, reaction
      temperature, H2O2:oil volume ratio and the reuse of catalyst on the catalytic
      oxidation desulfurization kinetics were investigated. The DBT conversion rate of
      the reaction catalyzed by supported HPW under ultrasound irradiation was higher
      than the summation of the reactions with HPW only and AC only as catalyst. With
      the increase of loading amount of HPW on AC, ultrasound power, H2O2:oil volume
      ratio and reaction temperature, the catalytic oxidation reactivity of DBT would
      be enhanced. The optimum loading amount of HPW was 10%, exceed which DBT
      conversion would no longer increase obviously. DBT could be completely converted
      under the optimized conditions (volume ratio of H2O2 to model oil: 1:10, mass
      ratio of the supported HPW to model oil: 1.25%, temperature: 70 degrees C) after
      9 min of ultrasound irradiation.

PMID- 24326222
TI  - Hypothermic endpoint for an intranasal invasive pulmonary aspergillosis mouse
      model.
AB  - Immunocompromised mice were infected intranasally with Aspergillus fumigatus as
      part of a vaccine efficacy study. Although body temperature was measured
      throughout the study, a formal evaluation of its usefulness as an endpoint
      criterion was not performed. We retrospectively evaluated survival data and
      temperature records to determine whether body temperature can be used as an
      objective predictor of death and included in the humane endpoint criteria for
      this mouse model. CF1 mice were immunosuppressed with either cortisone acetate or
      by treatment with antiGR1 (a neutrophil-depleting antibody) and then intranasally
      challenged with A. fumigatus. Body temperature was measured by using an infrared
      noncontact thermometer a maximum of 3 times daily until death or euthanasia. A
      surface body temperature below 29.0  degrees C was correlated with a poor chance
      of survival, and using this cutoff point with signs of morbidity (hunched,
      ruffled fur, respiratory distress) reliably indicates mice for euthanasia without
      negatively affecting data collection. Using 2 subsequent readings of less than
      31.0  degrees C as an endpoint would have led to premature euthanasia of only one
      mouse (2.2%). As a single reading, a body temperature of 28.8  degrees C had a
      sensitivity of 92.2% and specificity of 90.9%. Hypothermia proved to be a useful
      addition to the humane endpoint criteria for this mouse model, and veterinary and
      research groups should discuss their study needs in relation to animal welfare to
      best determine the most appropriate means of including this parameter. 

PMID- 24326223
TI  - Contrast agents for quantitative microCT of lung tumors in mice.
AB  - The identification and quantitative evaluation of lung tumors in mouse models is
      challenging and an unmet need in preclinical arena. In this study, we developed a
      noninvasive contrast-enhanced microCT (MUCT) method to longitudinally evaluate
      and quantitate lung tumors in mice. Commercially available MUCT contrast agents
      were compared to determine the optimal agent for visualization of thoracic blood
      vessels and lung tumors in naive mice and in non-small-cell lung cancer models.
      Compared with the saline control, iopamidol and iodinated lipid agents provided
      only marginal increases in contrast resolution. The inorganic nanoparticulate
      agent provided the best contrast and visualization of thoracic vascular
      structures; the density contrast was highest at 15 min after injection and was
      stable for more than 4 h. Differential contrast of the tumors, vascular
      structures, and thoracic air space by the nanoparticulate agent enabled
      identification of tumor margins and accurate quantification. MUCT data correlated
      closely with traditional histologic measurements (Pearson correlation
      coefficient, 0.995). Treatment of ELM4-ALK mice with crizotinib yielded 65%
      reduction in tumor size and thus demonstrated the utility of quantitative MUCT in
      longitudinal preclinical trials. Overall and among the 3 agents we tested, the
      inorganic nanoparticulate product was the best commercially available contrast
      agent for visualization of thoracic blood vessels and lung tumors. Contrast
      enhanced MUCT imaging is an excellent noninvasive method for longitudinal
      evaluation during preclinical lung tumor studies. 

PMID- 24326221
TI  - Animal models of Q fever (Coxiella burnetii).
AB  - Q fever, caused by the pathogen Coxiella burnetii, is an acute disease that can
      progress to become a serious chronic illness. The organism leads an obligate,
      intracellular lifecycle, during which it multiplies in the phagolytic
      compartments of the phagocytic cells of the immune system of its hosts. This
      characteristic makes study of the organism particularly difficult and is perhaps
      one of the reasons why, more than 70 y after its discovery, much remains unknown
      about the organism and its pathogenesis. A variety of animal species have been
      used to study both the acute and chronic forms of the disease. Although none of
      the models perfectly mimics the disease process in humans, each opens a window
      onto an important aspect of the pathology of the disease. We have learned that
      immunosuppression, overexpression of IL10, or physical damage to the heart muscle
      in mice and guinea pigs can induce disease that is similar to the chronic disease
      seen in humans, suggesting that this aspect of disease may eventually be fully
      understood. Models using species from mice to nonhuman primates have been used to
      evaluate and characterize vaccines to protect against the disease and may
      ultimately yield safer, less expensive vaccines. 

PMID- 24326224
TI  - A clinically translatable mouse model for chemotherapy-related fatigue.
AB  - Fatigue is a debilitating and pervasive complication of cancer and cancer care.
      Clinical research investigating potential therapies is hindered by variability in
      patient histories, different metrics for measuring fatigue, and environmental
      factors that may affect fatigue. The purpose of this study was to establish an
      animal model of chemotherapy-related fatigue. Female HSD:ICR mice were treated
      with doxorubicin (2.5 mg/kg) or saline in 2 cycles (days 1 through 3 and 10
      through 12). After treatment, mice were individually housed in cages equipped
      with running wheels. Open-field activity and motor coordination were examined
      after each cycle of treatment and after each week of wheel running. In a separate
      cohort, modafinil (50 mg/kg) was assessed as a potential treatment for fatigue.
      Doxorubicin administration resulted in greater than 30% less wheel running
      compared with that of saline controls. Activity differences were specific to
      wheel running: neither distance traveled in the open field nor motor coordination
      according to the rotarod test differed between groups. Compared with control
      values, RBC counts in the doxorubicin group were decreased on days 15 and 22 but
      recovered to control levels by study completion. Modafinil was efficacious in
      increasing wheel running in the doxorubicin group. The current results establish
      an animal model of chemotherapy-related fatigue that recapitulates the physical
      symptoms of cancer-related fatigue as manifested as decreased voluntary activity.
      This model is sensitive to pharmaceutical intervention and can be used to screen
      potential treatments for fatigue. 

PMID- 24326225
TI  - Age-related differences in collagen-induced arthritis: clinical and imaging
      correlations.
AB  - Arthritis is among the most common chronic diseases in both children and adults.
      Although intraarticular inflammation is the feature common among all patients
      with chronic arthritis there are, in addition to age at onset, clinical
      characteristics that further distinguish the disease in pediatric and adult
      populations. In this study, we aimed to demonstrate the utility of microCT (MUCT)
      and ultrasonography in characterizing pathologic age-related differences in a
      collagen-induced arthritis (CIA) rat model. Juvenile (35 d old) and young adult
      (91 d old) male Wistar rats were immunized with bovine type II collagen and
      incomplete Freund adjuvant to induce polyarthritis. Naive male Wistar rats served
      as controls. All paws were scored on a scale of 0 (normal paw) to 4 (disuse of
      paw). Rats were euthanized at 14 d after the onset of arthritis and the hindpaws
      imaged by MUCT and ultrasonography. Young adult rats had more severe signs of
      arthritis than did their juvenile counterparts. Imaging demonstrated that young
      adult CIA rats exhibited more widespread and severe skeletal lesions of the
      phalanges, metatarsals, and tarsal bones, whereas juvenile CIA rats had more
      localized and less proliferative and osteolytic damage that was confined
      predominantly to the phalanges and metatarsals. This report demonstrates the
      utility of imaging modalities to compare juvenile and young adult rats with CIA
      and provides evidence that disease characteristics and progression differ between
      the 2 age groups. Our observations indicate that the CIA model could help discern
      age-related pathologic processes in inflammatory joint diseases. 

PMID- 24326226
TI  - Enteric infection and subsequent septicemia due to attaching and effacing
      Escherichia coli in a Chinchilla.
AB  - An adult male chinchilla (Chinchilla lanigera) presented with severe lethargy and
      tachypnea; the physical examination was otherwise unremarkable. Due to the
      animal's clinical condition, it was submitted for necropsy but died immediately
      prior to euthanasia. Clinicopathologic findings included leukocytosis with a left
      shift neutrophilia and lymphopenia, azotemia, hyperphosphatemia, hyperglycemia,
      hyperlipemia, electrolyte imbalance, cholestasis, and hepatocellular damage.
      Neutrophilic enteritis with gramnegative bacterial colonization, hepatic
      lipidosis, interstitial pneumonia, suppurative tubulonephritis, erosive
      gastritis, cerebral edema, and lymphoid depletion were present microscopically.
      Attaching and effacing, eae-positive, Escherichia coli characterized by the
      presence of the intimin virulence factor was isolated from both the kidney and
      spleen. The cause of death was attributed to acute E. coli septicemia and
      subsequent disseminated intravascular coagulation. 

PMID- 24326227
TI  - Constitutive release of IFNgamma and IL2 from peripheral blood mononuclear cells
      of rhesus macaques (Macaca mulatta) infected with simian T-lymphotropic virus
      type 1.
AB  - Simian T-cell lymphotropic viruses (STLV), the nonhuman primate counterparts of
      human T-cell lymphotropic viruses (HTLV), are endemic in many populations of
      African and Asian monkeys and apes. Although an etiologic link between STLV1
      infection and lymphoproliferative disorders such as malignant lymphomas has been
      suggested in some nonhuman primate species, most STLV infections are inapparent,
      and infected animals remain clinically healthy. The retroviral transactivator,
      tax, is well known to increase transcription of viral and cellular genes,
      resulting in altered cytokine profiles. This study compared the cytokine profiles
      of peripheral blood mononuclear cell (PBMC) cultures from 25 STLV1-seropositive
      rhesus macaques (Macaca mulatta) with those of age- and sex-matched seronegative
      controls. IFNgamma, TNFalpha, IL10, and IL2 levels in unstimulated PBMC culture
      supernatants were measured at 24, 48, and 72 h by using enzyme immunoassays.
      IFNgamma concentrations were found significantly higher in the supernatants of
      PBMC cultures of seropositive monkeys as compared with seronegative controls. In
      addition, although IL2 concentrations were not significantly elevated in the
      supernatants of PBMC cultures of all seropositive monkeys as compared with all
      seronegative controls, IL2 levels were increased in a subset of 5 pairs.
      Increased constitutive cytokine release occurred in the absence of spontaneous
      proliferation. The increased constitutive release of IFNgamma and IL2 suggests
      that STLV1 alters immune functions in infected but clinically healthy rhesus
      macaques and further characterizes STLV1 infection of rhesus macaques as a
      potential model for human HTLV1 infection. 

PMID- 24326228
TI  - Cerebral amyloid angiopathy in an aged sooty mangabey (Cercocebus atys).
AB  - A 26-y-old male sooty mangabey (Cercocebus atys) was found at necropsy to have a
      moderate degree of cerebral amyloid beta (Abeta) angiopathy in superficial and
      parenchymal blood vessels of the brain. Senile (Abeta) plaques were absent, as
      were neurofibrillary tangles and other signs of neurodegeneration. Affected blood
      vessels were arterial, capillary, and, less frequently, venous in nature.
      Histologically, the Abeta40 isoform was more prevalent than was Abeta42. As in
      humans but unlike in squirrel monkeys, the density of lesions in this mangabey
      increased along a rostral-to-caudal gradient. Therefore mangabeys appear to
      conform to the general tendency of nonhuman primates by developing cerebral Abeta
      angiopathy in the absence of other indices of Alzheimer-type neuropathology. 

PMID- 24326229
TI  - Septic arthritis due to moraxella osloensis in a rhesus macaque (Macaca mulatta).
AB  - A 5.5-y-old Chinese-origin female rhesus macaque (Macaca mulatta) presented for
      bilateral hindlimb lameness. The primate had been group-reared in an SPF breeding
      colony and was seronegative for Macacine herpesvirus 1, SIV, simian retrovirus
      type D, and simian T-lymphotropic virus. The macaque's previous medical history
      included multiple occasions of swelling in the left tarsus, and trauma to the
      right arm and bilateral hands. In addition, the macaque had experienced
      osteomyelitis of the left distal tibia and rupture of the right cranial cruciate
      ligament that had been surgically repaired. Abnormal physical examination
      findings on presentation included a thin body condition, mild dehydration, and
      bilaterally swollen stifles that were warm to the touch, with the right stifle
      more severely affected. Mild instability in the left stifle was noted, and
      decreased range of motion and muscle atrophy were present bilaterally.
      Hematologic findings included marked neutrophilia and lymphopenia and moderate
      anemia. Arthrocentesis and culture of joint fluid revealed Moraxella-like
      organisms. Treatment with enrofloxacin was initiated empirically and subsequently
      switched to cephalexin, which over time alleviated the joint swelling and
      inflammation. Definitive diagnosis of Moraxella osloensis septic arthritis was
      made through isolation of the organism and sequencing of the 16S rDNA region. To
      our knowledge, this report is the first description of Moraxella osloensis septic
      arthritis in a rhesus macaque. 

PMID- 24326230
TI  - Natural infection of Burkholderia pseudomallei in an imported pigtail macaque
      (Macaca nemestrina) and management of the exposed colony.
AB  - Identification of the select agent Burkholderia pseudomallei in macaques imported
      into the United States is rare. A purpose-bred, 4.5-y-old pigtail macaque (Macaca
      nemestrina) imported from Southeast Asia was received from a commercial vendor at
      our facility in March 2012. After the initial acclimation period of 5 to 7 d,
      physical examination of the macaque revealed a subcutaneous abscess that
      surrounded the right stifle joint. The wound was treated and resolved over 3 mo.
      In August 2012, 2 mo after the stifle joint wound resolved, the macaque exhibited
      neurologic clinical signs. Postmortem microbiologic analysis revealed that the
      macaque was infected with B. pseudomallei. This case report describes the
      clinical evaluation of a B. pseudomallei-infected macaque, management and care of
      the potentially exposed colony of animals, and protocols established for the
      animal care staff that worked with the infected macaque and potentially exposed
      colony. This article also provides relevant information on addressing matters
      related to regulatory issues and risk management of potentially exposed animals
      and animal care staff. 

PMID- 24326232
TI  - Cytotoxicity and morphological effects induced by carvacrol and thymol on the
      human cell line Caco-2.
AB  - Essential oils used as additives in the food industry due to its flavour,
      antimicrobial and antioxidant properties. Therefore, human can be exposed orally
      to these compounds through the ingestion of foods. In this sense, the present
      work aims to assess toxicological effects of oregano essential oil on the
      digestive tract. In concrete, the cytotoxic effects of two components of the
      oregano essential oils, carvacrol and thymol, and their mixture, on the
      intestinal cells line Caco-2 after 24 and 48 h of exposure are studied. The basal
      cytotoxicity endpoints assayed (total protein content, neutral red uptake and the
      tetrazolium salt reduction) and the annexin/propidium iodide staining indicated
      that carvacrol and the mixture carvacrol/thymol induced toxic effects. Moreover,
      a morphological study was performed in order to determine the ultrastructural
      cellular damages caused by these substances. The main morphological alterations
      were vacuolated cytoplasm, altered organelles and finally cell death. In
      addition, although no cytotoxic effects were recorded for thymol at any
      concentration and time of exposure, ultrastructural changes evidenced cellular
      damage such as lipid degeneration, mitochondrial damage, nucleolar segregation
      and apoptosis.

PMID- 24326231
TI  - Antibiotic resistances of intestinal lactobacilli isolated from wild boars.
AB  - Acquired antibiotic resistances have been reported in lactobacilli of various
      animal and food sources, but there are no data from wild boar. The objective was
      a preliminary examination of the antibiotic resistance prevalence of
      intrinsically vancomycin-resistant lactobacilli isolated from wild boar
      intestines and analysis of the genetic determinants implicated. Out of three wild
      boars, 121 lactobacilli were recovered and grouped according to their whole cell
      protein patterns. Initial phenotypic screening revealed that all were susceptible
      to erythromycin (2 MUg/ml), but 30 were resistant to tetracycline (32 MUg/ml).
      Based on Randomly Amplified Polymorphic DNA-PCR clustering, 64 strains were
      selected as representative genotypes for identification and minimum inhibitory
      concentration (MIC) determination. Partial 16S rRNA gene sequencing identified
      four species: (i) L. mucosae (n=57), (ii) L. reuteri (n=47), (iii) L. fermentum
      (n=12), and (iv) L. murinus (n=5). Most heterofermentative strains displayed low
      MICs for ampicillin (AMP), chloramphenicol (CHL), streptomycin (STR), kanamycin
      (KAN), gentamicin (GEN), erythromycin (ERY), quinupristin/dalfopristin (Q/D), and
      clindamycin (CLI). Atypical MICs were found mainly in L. mucosae and L. reuteri
      for TET, KAN, STR, AMP and CHL, but except the TET MICs of L. mucosae mostly at
      low level. L. murinus strains revealed atypical MICs for aminoglycosides, and/or
      CHL, AMP, CLI. PCR screening detected tet(W) in 12 and tet(M) in one of
      heterofermentative strains, as well as the aph(3')-III kanamycin gene in L.
      murinus. This is the first report showing acquired antibiotic resistance
      determinants in intestinal lactobacilli of wild boar origin.

PMID- 24326233
TI  - Sequence of onset latency of body segments when turning on-the-spot in people
      with stroke.
AB  - BACKGROUND: Turning around is a common activity of daily living. The location of
      a target may be known or unknown while angle and direction may vary prior to
      turning. A stroke can compromise coordination of body movement during turning.
      OBJECTIVES: To investigate the effect of target predictability, turn angle and
      turn direction on the kinematic sequence of rotation of body segments in people
      with stroke and healthy controls when turning on-the-spot. METHODS: Ten people
      with stroke (age: 66+/-10 years; 8 males) and 10 age-matched controls (age: 65+/
      8 years; 6 males) were asked to either turn to a specific light (predictable
      condition) or locate and turn to a random light (unpredictable condition) placed
      at 45 degrees , 90 degrees  or 135 degrees  to the right or left when a light in
      front extinguished. RESULTS: People with stroke initiated movement of the
      segments significantly later than the controls (p=0.014). The sequence of onset
      of rotation of the segments was not different between both groups. Target
      predictability affected the sequence of the segments; the eyes, head and shoulder
      started moving simultaneously when turning to unpredictable targets while the
      head and shoulder started moving before the eyes when turning to predictable
      targets. The sequence was also different across the three turn angles for each
      predictability condition. However, the sequence remained the same when turning to
      both sides in each group. CONCLUSION: Similarities between the groups may be
      because the time since the stroke was long and therefore some recovery of
      function may have occurred. Slowness of movement in people with stroke may
      predispose them to falls.

PMID- 24326235
TI  - Do nocturnal headaches matter? A prospective diary study on subjective sleep
      parameters in snorers and their bed partners.
AB  - BACKGROUND: The objective of this study was to assess the influence of nocturnal
      headaches (NH) on subjective sleep parameters prospectively in habitual snorers
      and their bed partners. METHODS: We recruited habitual snorers and their bed
      partners via newspaper articles. The participants completed a semistructured
      interview, filled in questionnaires about quality of sleep (PSQI), daytime
      sleepiness (ESS), depression (SDS) and anxiety (SAS) and they kept a 90-day
      headache and sleep diary. RESULTS: Seventy-six snorers (25 female) and 41 bed
      partners (31 female) completed the study recording a total of 6690 and 3497 diary
      days, respectively. NH were recorded on 222 (3.3%) and 79 (2.2%) days in 32 (42%)
      snorers and 17 (41%) bed partners, respectively. Snorers with NH showed
      significantly higher PSQI (5 +/- 3 vs. 4 +/- 2, p = 0.004), SAS (38 +/- 11 vs. 31
      +/- 10, p = 0.011) and SDS scores (39 +/- 12 vs. 34 +/- 10, p = 0.048) than
      snorers without NH. For bed partners with NH we found a significant female
      predominance (sex ratio f:m = 16:1 vs. 12:12, p = 0.005) and significantly higher
      SAS scores (38 +/- 6 vs. 33 +/- 8, p = 0.030) compared with bed partners without
      NH. The subjective quality of sleep in habitual snorers (p < 0.001) as well as
      their bed partners (p = 0.017) was negatively influenced by NH, but not total
      sleep time. DISCUSSION: NH occurred in around 40% of snorers and their bed
      partners at least once during the 90-day observation period. Our results
      confirmed a negative impact on the subjective quality of sleep in both groups.

PMID- 24326234
TI  - Mesenchymal stem cell secreted platelet derived growth factor exerts a pro
      migratory effect on resident Cardiac Atrial appendage Stem Cells.
AB  - Mesenchymal stem cells (MSCs) modulate cardiac healing after myocardial injury
      through the release of paracrine factors, but the exact mechanisms are still
      unknown. One possible mechanism is through mobilization of endogenous cardiac
      stem cells (CSCs). This study aimed to test the pro-migratory effect of MSC
      conditioned medium (MSC-CM) on endogenous CSCs from human cardiac tissue. By
      using a three-dimensional collagen assay, we found that MSC-CM improved migration
      of cells from human cardiac tissue. Cell counts, perimeter and area measurements
      were utilized to quantify migration effects. To examine whether resident stem
      cells were among the migrating cells, specific stem cell properties were
      investigated. The migrating cells displayed strong similarities with resident
      Cardiac Atrial appendage Stem Cells (CASCs), including a clonogenic potential of
      ~21.5% and expression of pluripotency associated genes like Oct-4, Nanog, c-Myc
      and Klf-4. Similar to CASCs, migrating cells demonstrated high aldehyde
      dehydrogenase activity and were able to differentiate towards cardiomyocytes.
      Receptor tyrosine kinase analysis and collagen assays performed with recombinant
      platelet derived growth factor (PDGF)-AA and Imatinib Mesylate, a PDGF receptor
      inhibitor, suggested a role for the PDGF-AA/PDGF receptor alpha axis in enhancing
      the migration process of CASCs. In conclusion, our findings demonstrate that
      factors present in MSC-CM improve migration of resident stem cells from human
      cardiac tissue. These data open doors towards future therapies in which MSC
      secreted factors, like PDGF-AA, can be utilized to enhance the recruitment of
      CASCs towards the site of myocardial injury. 

PMID- 24326236
TI  - Randomized, proof-of-principle clinical trial of active transcranial magnetic
      stimulation in chronic migraine.
AB  - BACKGROUND: High-frequency repetitive transcranial magnetic stimulation of the
      left dorsolateral prefrontal cortex (rTMS-DLPFC) is an effective treatment for
      depression. Preliminary studies indicated beneficial effects of rTMS-DLPFC on
      pain relief in patients treated for depression, and in patients with chronic
      migraine. METHODS: In this randomized, double-blind, parallel-group, single
      center, proof-of-principle clinical trial, we tested the hypothesis that 23
      sessions of active rTMS-DLPFC delivered over eight weeks would be feasible, safe
      and superior to sham rTMS to decrease the number of headache days in 18 patients
      with chronic migraine without severe depression. Per-protocol analysis was
      performed. RESULTS: rTMS-DLPFC applied over eight weeks was feasible and safe in
      patients with chronic migraine. Contrary to our primary hypothesis, the number of
      headache days decreased significantly more in the sham group than in the group
      treated with active rTMS-DLPFC at eight weeks. Average decrease in headache days
      was >50% in the sham group, indicating a powerful placebo response. Pain
      intensity improved in both groups to a similar extent. CONCLUSIONS: Positive
      results of M1 stimulation in other studies, and the absence of significant
      benefits of active high-frequency rTMS of the DLPFC in the present study, point
      to M1 as a more promising target than the DLPFC, for larger trials of noninvasive
      brain stimulation in patients with chronic migraine.

PMID- 24326237
TI  - Long-term follow-up of home-based behavioral management training provided by
      migraine patients.
AB  - BACKGROUND: Behavioral migraine approaches are effective in reducing headache
      attacks. Availability of treatment might be increased by using migraine patients
      as trainers. Therefore, Merelle and colleagues developed and evaluated a home
      based behavioral management training (BMT) by lay trainers (1). The maintenance
      of effects at long-term follow-up is studied in the present study. METHOD:
      Measurements were taken pre-BMT (T0), post-BMT (T1), at six-month follow-up (T2),
      and at long-term follow-up, i.e. two to four years after BMT (T3). Data of 127
      participants were analyzed with longitudinal multi-level analyses. RESULTS: Short
      term improvements in attack frequency and self-efficacy post-BMT were maintained
      at long-term follow-up ( DT0T3  = -.34 and DT0T3  = .69, respectively). The level
      of internal control that increased during BMT decreased from post-BMT to long
      term follow-up ( DT0T3  = .18). Quality of life and migraine-related disability
      improved gradually over time ( DT0T3  = .45 and DT0T3  = -.26, respectively).
      CONCLUSIONS: Although the results should be interpreted with caution because of
      the lack of a follow-up control group and the inability to gather information
      about additional treatments patients may have received during the follow-up
      period, the findings suggest that lay BMT for migraine may be beneficial over the
      long term. If so, this could make migraine treatments more widely available.

PMID- 24326238
TI  - Aortic perforation during lateral lumbar interbody fusion.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To report a unique case of aortic
      perforation during lateral lumbar interbody fusion (LLIF). SUMMARY OF BACKGROUND
      DATA: Among the reported advantages of this minimally invasive transpsoas
      procedure is the avoidance of an anterior intraperitoneal approach to the lumbar
      spine, thus avoiding visceral and vascular injuries typically associated with the
      latter. METHODS: We report a single case of aortic perforation during LLIF, which
      occurred in the setting of an incidental endplate and anterior vertebral cortex
      violation. RESULTS: During the implantation of an interbody prosthetic device at
      the L3-L4 level, the proximal aspect of the implant broke which caused cage
      misplacement. During the attempt to advance the well-fixed cage, distal violation
      of the endplate and anterior cortex of the L3 vertebra was noted, concomitant
      with immediate loss of blood pressure. A presumptive diagnosis of injury to a
      major vascular structure was quickly made, along with the decision to proceed
      with emergency laparotomy to repair a through-and-through laceration of the
      aortic terminus. After successful suture repair of the aortic lesions, the
      patient was kept intubated, and transferred to the intensive care unit in stable
      condition. CONCLUSIONS: The distal endplate and anterior vertebral cortex
      violation can result in the formation of an anterior bony spur in close proximity
      to the major abdominal vascular structures, and despite the avoidance of an
      anterior approach to the lumbar spine, surgery-related injury to major abdominal
      vessels can occur during LLIF. Aortic perforation is a rare, yet potentially
      lethal intraoperative complication of LLIF, which requires emergency laparatomy
      and vascular suture repair.

PMID- 24326240
TI  - Incidental dural tear in cervical spine surgery: analysis of a nationwide
      database.
AB  - STUDY DESIGN: This was a retrospective study. OBJECTIVE: To report the incidence
      of incidental dural tear (DT) in cervical spine surgery, risk factors, and in
      hospital patient outcomes on a national level. SUMMARY OF BACKGROUND DATA: DT
      during cervical spine surgery is not as common as that during lumbar spine
      surgery; however, DT is still a difficult complication. METHODS: Clinical data
      were obtained from the US Nationwide Inpatient Sample for 2009. Patients who
      underwent cervical spine surgery were identified and divided into those with and
      without DT according to the International Classification of Diseases, 9th
      revision, Clinical Modification codes. The patient and health care system-related
      demographic data were retrieved. The incidence of DT and patient outcomes were
      analyzed. A multivariate logistic regression analysis was performed to identify
      the risk factors for DT. RESULTS: The incidence of DT was 0.45% (855/190,021).
      The multivariate analysis revealed that a diagnosis of myelopathy and
      ossification of the posterior longitudinal ligament; posterior approach, anterior
      and posterior approach; and insurance status were the significant risk factors
      for DT. Comparison between patients with and without DT showed that those with DT
      had significantly higher overall in-hospital complications (21.6% vs. 7.3%),
      longer hospital stays (6.0 vs. 3.2 d), a lower proportion who were discharged
      home routinely (66.3% vs. 83.9%), increased total hospital costs ($96,424 vs.
      $62,416), and similar in-hospital mortality (0.6% vs. 0.4%). CONCLUSIONS: The
      incidence of DT in cervical spine surgery was 0.45% in the United States. The
      risk of DT was highest with a primary diagnosis of the ossification of the
      posterior longitudinal ligament (58.4 times). DT significantly increased the rate
      of in-hospital complications and health care burden.

PMID- 24326241
TI  - Surgical Treatment for Thoracic Myelopathy Due to Simultaneous Ossification of
      the Posterior Longitudinal Ligament and Ligamentum Flavum at the Same Level.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: The aim of this study was to
      assess the clinical outcomes of surgery in patients with simultaneous
      ossification of the posterior longitudinal ligament (OPLL) and ossification of
      the ligamentum flavum (OLF) at the same thoracic spine level and identify the
      risk factors for poor outcomes. SUMMARY OF BACKGROUND DATA: OPLL complicated with
      OLF in the thoracic spine is a rare condition. The optimal treatment option for
      thoracic myelopathy due to OPLL and OLF remains controversial, and high risk of
      postoperative paralysis remains a major complication. METHODS: We conducted a
      retrospective review of clinical and radiographic records of 15 patients who
      underwent surgery for simultaneous OPLL and OLF at the same level. RESULTS:
      Simultaneous OPLL and OLF occurred in the upper thoracic spine in 3 patients
      (20%), mid-thoracic spine in 10 patients (67%), and lower thoracic spine in 2
      patients (13%). Six, 4, 2, and 3 patients underwent posterior decompression,
      posterior decompression and fusion, posterior decompression and circumferential
      decompression through a posterior approach, and circumferential decompression and
      posterior fusion, respectively. The mean Japanese Orthopaedic Association score
      before surgery and at the final follow-up was 5.7+/-1.9 and 7.0+/-2.1 points,
      respectively, yielding a mean recovery rate of 16.5%. However, no significant
      difference was observed between preoperative and postoperative Japanese
      Orthopaedic Association scores. Two patients with mid-thoracic lesions reported
      postoperative lower extremity weakness. Mid-thoracic lesions and considerable
      blood loss were risk factors for poor surgical outcome. CONCLUSIONS: Simultaneous
      OPLL and OLF in the mid-thoracic spine was observed in two thirds of the
      patients. We suggest that simultaneous OPLL and OLF in this area has a relatively
      poor recovery and may be very challenging and risky to treat, regardless of the
      surgical method selected, and recommend early surgery for OPLL and OLF in the mid
      thoracic spine.

PMID- 24326242
TI  - Incidence of Dysphagia and Serial Videofluoroscopic Swallow Study Findings After
      Anterior Cervical Discectomy and Fusion: A Prospective Study.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To prospectively assess the incidence
      of dysphagia and to present the serial changes of each finding in the
      videofluoroscopic swallow study (VFSS) after anterior cervical discectomy and
      fusion (ACDF). SUMMARY OF BACKGROUND DATA: The reported incidence of dysphagia
      after ACDF has varied widely, and the serial changes of dysphagia using VFSS have
      not been clearly determined yet. METHODS: Data of 47 patients preoperatively and
      at 1 week and 1 month postoperatively were used for the analyses. The Bazaz
      dysphagia score and VFSS were checked preoperatively and at 1 week and 1 month
      postoperatively. The presence of aspiration or penetration, amount of vallecular
      and pyriform sinus residues, functional dysphagia scale, temporal parameters of
      oral transit time, pharyngeal transit time, and pharyngeal delay time (PDT) were
      evaluated from the VFSS data. RESULTS: Incidences of dysphagia measured by the
      Bazaz dysphagia score were 83.0% at 1 week and 59.6% at 1 month after ACDF.
      Although the incidence of aspiration was 4.3% and the incidence of penetration
      was 36.2% at 1 week and 25.5% at 1 month after surgery, none of the patients had
      aspiration pneumonia. The number of patients with vallecular and pyriform sinus
      residues significantly increased after ACDF. Further, there were no statistically
      significant changes at all time points in terms of oral transit time, pharyngeal
      transit time, and pharyngeal delay time. CONCLUSIONS: Dysphagia is common until 1
      month after ACDF. Although the incidence of aspiration or penetration in VFSS
      after ACDF was high, no patient had aspiration pneumonia, which may be because of
      the intact neurological swallowing mechanism. The typical pattern of dysphagia
      after ACDF included vallecular and pyriform sinuses filled with postswallow
      residue, which may result from soft tissue edema and weak constriction of
      pharyngeal muscles after ACDF.

PMID- 24326243
TI  - [Facial paralysis secondary to single metastasis to the temporal bone from
      bladder cancer].

PMID- 24326244
TI  - Effects of environmental enrichment on growth, aggressive behaviour and brain
      monoamines of gilthead seabream Sparus aurata reared under different social
      conditions.
AB  - The presence of blue or red-brown substrate on the tank bottom has been
      previously reported as an efficient means of environmental enrichment for
      gilthead seabream. The present study aimed to investigate whether this enrichment
      is still beneficial when gilthead seabream is reared under different social
      conditions (i.e. a lower 4.9 kg m(-3) and a higher 9.7 kg m(-3) density). Water
      exchange was adjusted according to fish biomass to exclude density effects on
      water quality. In the enriched tanks single-colour glass gravel was used as
      substrate (blue and red-brown substrate, or BS and RBS respectively), while
      control tanks had no gravel. Growth, aggressive behaviour and size distribution
      results indicated that the lower density created a less favourable social
      environment. In both densities studied, BS enhanced growth, suppressed aggression
      and reduced brain serotonergic activity. In the condition of intense social
      interactions (i.e. the lower density) BS also reduced brain dopaminergic
      activity. These results along with the negative correlations observed between
      brain monoamines and fish body mass, indicated that substrate and density effects
      are socially-induced. However, there may be several biotic and/or abiotic factors
      interfering with substrate effects that should be investigated before the
      practical use of a substrate in land-based intensive aquaculture.

PMID- 24326245
TI  - Simulation of the planetary interior differentiation processes in the laboratory.
AB  - A planetary interior is under high-pressure and high-temperature conditions and
      it has a layered structure. There are two important processes that led to that
      layered structure, (1) percolation of liquid metal in a solid silicate matrix by
      planet differentiation, and (2) inner core crystallization by subsequent planet
      cooling. We conduct high-pressure and high-temperature experiments to simulate
      both processes in the laboratory. Formation of percolative planetary core depends
      on the efficiency of melt percolation, which is controlled by the dihedral
      (wetting) angle. The percolation simulation includes heating the sample at high
      pressure to a target temperature at which iron-sulfur alloy is molten while the
      silicate remains solid, and then determining the true dihedral angle to evaluate
      the style of liquid migration in a crystalline matrix by 3D visualization. The 3D
      volume rendering is achieved by slicing the recovered sample with a focused ion
      beam (FIB) and taking SEM image of each slice with a FIB/SEM crossbeam
      instrument. The second set of experiments is designed to understand the inner
      core crystallization and element distribution between the liquid outer core and
      solid inner core by determining the melting temperature and element partitioning
      at high pressure. The melting experiments are conducted in the multi-anvil
      apparatus up to 27 GPa and extended to higher pressure in the diamond-anvil cell
      with laser-heating. We have developed techniques to recover small heated samples
      by precision FIB milling and obtain high-resolution images of the laser-heated
      spot that show melting texture at high pressure. By analyzing the chemical
      compositions of the coexisting liquid and solid phases, we precisely determine
      the liquidus curve, providing necessary data to understand the inner core
      crystallization process. 

PMID- 24326246
TI  - The influence of averageness on judgments of facial attractiveness: no own-age or
      own-sex advantage among children attending single-sex schools.
AB  - We examined how recent biased face experience affects the influence of
      averageness on judgments of facial attractiveness among 8- and 9-year-old
      children attending a girls' school, a boys' school, and a mixed-sex school. We
      presented pairs of individual faces in which one face was transformed 50% toward
      its group average, whereas the other face was transformed 50% away from that
      average. Across blocks, the faces varied in age (adult, 9-year-old, or 5-year
      old) and sex (male or female). We expected that averageness might influence
      attractiveness judgments more strongly for same-age faces and, for children
      attending single-sex schools, same-sex faces of that age because their
      prototype(s) should be best tuned to the faces they see most frequently.
      Averageness influenced children's judgments of attractiveness, but the strength
      of the influence was not modulated by the age of the face, nor did the effects of
      sex of face differ across schools. Recent biased experience might not have
      affected the results because of similarities between the average faces of
      different ages and sexes and/or because a minimum level of experience with a
      particular group of faces may be adequate for the formation of a veridical
      prototype and its influence on judgments of attractiveness. The results suggest
      that averageness affects children's judgments of the attractiveness of the faces
      they encounter in everyday life regardless of age or sex of face. 

PMID- 24326247
TI  - Synthesis of 2.3 mg/ml of protein with an all Escherichia coli cell-free
      transcription-translation system.
AB  - Cell-free protein synthesis is becoming a useful technique for synthetic biology.
      As more applications are developed, the demand for novel and more powerful in
      vitro expression systems is increasing. In this work, an all Escherichia coli
      cell-free system, that uses the endogenous transcription and translation
      molecular machineries, is optimized to synthesize up to 2.3 mg/ml of a reporter
      protein in batch mode reactions. A new metabolism based on maltose allows
      recycling of inorganic phosphate through its incorporation into newly available
      glucose molecules, which are processed through the glycolytic pathway to produce
      more ATP. As a result, the ATP regeneration is more efficient and cell-free
      protein synthesis lasts up to 10 h. Using a commercial E. coli strain, we show
      for the first time that more than 2 mg/ml of protein can be synthesized in run
      off cell-free transcription-translation reactions by optimizing the energy
      regeneration and waste products recycling. This work suggests that endogenous
      enzymes present in the cytoplasmic extract can be used to implement new metabolic
      pathways for increasing protein yields. This system is the new basis of a cell
      free gene expression platform used to construct and to characterize complex
      biochemical processes in vitro such as gene circuits. 

PMID- 24326249
TI  - Galectin-3 interactions with glycosphingolipids.
AB  - Galectins have essential roles in pathological states including cancer,
      inflammation, angiogenesis and microbial infections. Endogenous receptors include
      members of the lacto- and neolacto-series glycosphingolipids present on mammalian
      cells and contain the tetrasaccharides lacto-N-tetraose (LNT) and lacto-N
      neotetraose (LNnT) that form their core structural components and also ganglio
      series glycosphingolipids. We present crystallographic structures of the
      carbohydrate recognition domain of human galectin-3, both wild type and a mutant
      (K176L) that influenced ligand affinity, in complex with LNT, LNnT and acetamido
      ganglioside a-GM3 (alpha2,3-sialyllactose). Key structural features revealed
      include galectin-3's demonstration of a binding mode towards gangliosides
      distinct from that to the lacto/neolacto-glycosphingolipids, with its capacity
      for recognising the core beta-galactoside region being challenged when the core
      oligosaccharide epitope of ganglio-series glycosphingolipids (GM3) is embedded
      within particular higher-molecular-weight glycans. The lacto- and neolacto-
      glycosphingolipids revealed different orientations of their terminal galactose in
      the galectin-3-bound LNT and LNnT structures that has significant ramifications
      for the capacity of galectin-3 to interact with higher-order lacto/neolacto
      series glycosphingolipids such as ABH blood group antigens and the HNK-1 antigen
      that is common on leukocytes. LNnT also presents an important model for poly-N
      acetyllactosamine-containing glycans and provides insight into galectin-3's
      accommodation of extended oligosaccharides such as the poly-N-acetyllactosamine
      modified N- and O-glycans that, via galectin-3 interaction, facilitate
      progression of lung and bladder cancers, respectively. These findings provide the
      first atomic detail of galectin-3's interactions with the core structures of
      mammalian glycosphingolipids, providing information important in understanding
      the capacity of galectin-3 to engage with receptors identified as facilitators of
      major disease.

PMID- 24326248
TI  - An unusual mode of galactose recognition by a family 32 carbohydrate-binding
      module.
AB  - Carbohydrate-binding modules (CBMs) are ancillary modules commonly associated
      with carbohydrate-active enzymes (CAZymes) that function to mediate the adherence
      of the parent enzyme to its carbohydrate substrates. CBM family 32 (CBM32) is one
      of the most diverse CBM families, whose members are commonly found in bacterial
      CAZymes that modify eukaryotic glycans. One such example is the putative MU
      toxin, CpGH84A, of the family 84 glycoside hydrolases, which comprises an N
      terminal putative beta-N-acetylglucosaminidase catalytic module and four tandem
      CBM32s. Here, we report a unique mode of galactose recognition by the first
      CBM32, CBM32-1 from CpGH84A. Solution NMR-based analyses of CpGH84A CBM32-1
      indicate a divergent subset of residues, located in ordered loops at the apex of
      the CBM, conferring specificity for the galacto-configured sugars galactose,
      GalNAc, and LacNAc that differs from those of the canonical galactose-binding
      CBM32s. This study showcases the impressive variability in ligand binding by this
      CBM family and offers insight into the growing role of these modules in the
      interaction of CAZymes with eukaryotic glycans. 

PMID- 24326250
TI  - Innate antiviral immune signaling, viral evasion and modulation by HIV-1.
AB  - The intracellular innate antiviral response in human cells is an essential
      component of immunity against virus infection. As obligate intracellular
      parasites, all viruses must evade the actions of the host cell's innate immune
      response in order to replicate and persist. Innate immunity is induced when
      pathogen recognition receptors of the host cell sense viral products including
      nucleic acid as "non-self". This process induces downstream signaling through
      adaptor proteins to activate latent transcription factors that drive the
      expression of genes encoding antiviral and immune modulatory effector proteins
      that restrict virus replication and regulate adaptive immunity. The interferon
      regulatory factors (IRFs) are transcription factors that play major roles in
      innate immunity. In particular, IRF3 is activated in response to infection by a
      range of viruses including RNA viruses, DNA viruses and retroviruses. Among these
      viruses, human immunodeficiency virus type 1 (HIV-1) remains a major global
      health problem mediating chronic infection in millions of people wherein recent
      studies show that viral persistence is linked with the ability of the virus to
      dysregulate and evade the innate immune response. In this review, we discuss
      viral pathogen sensing, innate immune signaling pathways and effectors that
      respond to viral infection, the role of IRF3 in these processes and how it is
      regulated by pathogenic viruses. We present a contemporary overview of the
      interplay between HIV-1 and innate immunity, with a focus on understanding how
      innate immune control impacts infection outcome and disease. 

PMID- 24326252
TI  - Comment on: Marginal zone lymphoma of the thoracic dura causing spinal cord
      compression (Dey et al.).

PMID- 24326253
TI  - Sonication of catheter tips for improved detection of microorganisms on external
      ventricular drains and ventriculo-peritoneal shunts.
AB  - The diagnosis of infections involving internal or external neurosurgical drainage
      devices is challenging, and to our knowledge no single reliable microbiological
      test exists. We used sonication to study bacterial colonization in 14 explanted
      external ventricular drains (EVD) and 13 ventriculo-peritoneal shunt (VPS)
      devices. This technique dislodges biofilm bacteria from the surface of implanted
      materials before culture. Removed devices were sonicated in saline (40 kHz, 1
      minute, 0.25 W/cm(2)), the resulting fluid was cultured aerobically and
      anaerobically at 37 degrees C, and bacterial growth was counted. Ventricular
      cerebrospinal fluid (CSF) was cultured separately. In the EVD group, sonication
      cultures grew significantly more bacteria (64%, 9/14) than cultures of aspirated
      ventricular CSF (14%, 2/14). In the VPS group the difference was not significant.
      Positive sonication cultures of EVD catheters yielded a median of >100 colony
      forming units (CFU) (range, 60-800). For positive sonication cultures of VPS, the
      median was 1000 CFU (range, 20-100,000). All patients with bacteria in their CSF
      also had positive sonication cultures from the removed device. Of the five
      patients with sterile or presumably contaminated CSF cultures but positive
      sonication cultures of removed shunts, one became afebrile after removal of the
      EVD, two developed meningitis and two remained asymptomatic. Sonication culture
      of EVD appears to improve the microbiological assessment of device-related
      infection and it corroborates with CSF cultures of revision surgery for VPS.
      Sonication of the removed EVD tip may raise awareness for the onset of
      meningitis.

PMID- 24326254
TI  - Surgical training technology for cerebrovascular anastomosis.
AB  - Cerebrovascular anastomosis (for example in the management of Moyamoya disease or
      complex aneurysms) is a rarely performed but essential procedure in neurosurgery.
      Because of the complexity of this technique and the infrequent clinical
      opportunities to maintain skills relevant to this surgery, laboratory training is
      important to develop a consistent and competent performance of cerebrovascular
      anastomosis. We reviewed the literature pertaining to the training practices
      surrounding cerebrovascular anastomosis in order to understand the ways in which
      trainees should best develop these skills. A wide variety of training methods
      have been described. These may be classified into five general categories,
      according to training materials used, being synthetic material, living animal,
      animal carcass, human cadaver, and computer simulation. Ideally, a novice begins
      training with non-biological material. After gaining sufficient dexterity, the
      trainee will be able to practice using biological materials followed by high
      fidelity models prior to actual surgery. Unfortunately, the effectiveness of each
      model has generally, to our knowledge, only been judged subjectively. Objective
      quantification methods are necessary to accelerate the acquisition of competence.

PMID- 24326255
TI  - Feasibility of the mini-open vertebral column resection for severe thoracic
      kyphosis.
AB  - Severe thoracic kyphosis caused by pathologic fractures often needs to be
      corrected by resection of the collapsed vertebral body, reconstruction of the
      anterior spinal column, and correction of the kyphosis with long-segment
      fixation. The resection of this pathologic bone functions essentially as a
      vertebral column resection. With the advent of minimally invasive technology, the
      powerful corrective forces afforded in open cases can be applied using a less
      invasive approach. In this article, we describe a mini-open posterior technique
      for thoracic kyphosis via a vertebrectomy and cantilever technique. Two patients
      underwent kyphosis correction via mini-open vertebrectomy. One patient was
      corrected from 92 degrees to 65 degrees, and the second patient was corrected
      from 70 degrees to 53 degrees. Both patients underwent a mini-open approach.
      Cantilever correction was accomplished over an expandable cage with a minimally
      invasive pedicle screw system. We describe our technique of mini-open vertebral
      column resection and kyphosis correction in the thoracic spine.

PMID- 24326257
TI  - Serum level of IL-10 is increased in patients with endometriosis, and IL-10
      promotes the growth of lesions in a murine model.
AB  - Immune dysregulation may be involved in the development of endometriosis. The
      anti-inflammatory cytokine IL-10 plays an important role in eliminating unwanted
      cells and cellular debris in a silent way. We investigated the modulatory role of
      IL-10 in the development of endometriosis. We observed that the serum level of IL
      10 in patients with endometriosis was significantly higher than that in healthy
      subjects or in control subjects with other gynecological disease. Monocyte
      derived dendritic cells acquired from male donors and subsequently conditioned
      with serum from women with endometriosis exhibited a tolerogenic phenotype,
      including increased IL-10 production, lower IL-12 secretion, and down-regulation
      of CD86 and HLA-DR molecules. Depletion of IL-10 activity in a C57BL/6 mouse
      model of surgically induced endometriosis significantly decreased the size of
      endometrial lesions. In contrast, IL-10 administration promoted the growth of
      endometrial lesions in this model. In addition, infiltrated plasmacytoid
      dendritic cells were the primary IL-10-secreting immune cells in endometrial
      lesions. Our findings suggest that IL-10 may suppress immunity against
      endometrial implants, contributing to development of endometriosis. 

PMID- 24326258
TI  - Experimental design based response surface methodology optimization of ultrasonic
      assisted adsorption of safaranin O by tin sulfide nanoparticle loaded on
      activated carbon.
AB  - In this research, the adsorption rate of safranine O (SO) onto tin sulfide
      nanoparticle loaded on activated carbon (SnS-NPAC) was accelerated by the
      ultrasound. SnS-NP-AC was characterized by different techniques such as SEM, XRD
      and UV-Vis measurements. The present results confirm that the ultrasound assisted
      adsorption method has remarkable ability to improve the adsorption efficiency.
      The influence of parameters such as the sonication time, adsorbent dosage, pH and
      initial SO concentration was examined and evaluated by central composite design
      (CCD) combined with response surface methodology (RSM) and desirability function
      (DF). Conducting adsorption experiments at optimal conditions set as 4 min of
      sonication time, 0.024 g of adsorbent, pH 7 and 18 mg L(-1) SO make admit to
      achieve high removal percentage (98%) and high adsorption capacity (50.25 mg g(
      )(1)). A good agreement between experimental and predicted data in this study was
      observed. The experimental equilibrium data fitting to Langmuir, Freundlich,
      Tempkin and Dubinin-Radushkevich models show that the Langmuir model is a good
      and suitable model for evaluation and the actual behavior of adsorption. Kinetic
      evaluation of experimental data showed that the adsorption processes followed
      well pseudo-second-order and intraparticle diffusion models.

PMID- 24326256
TI  - Loss of caveolin-1 causes blood-retinal barrier breakdown, venous enlargement,
      and mural cell alteration.
AB  - Blood-retinal barrier (BRB) breakdown and related vascular changes are implicated
      in several ocular diseases. The molecules and mechanisms regulating BRB integrity
      and pathophysiology are not fully elucidated. Caveolin-1 (Cav-1) ablation results
      in loss of caveolae and microvascular pathologies, but the role of Cav-1 in the
      retina is largely unknown. We examined BRB integrity and vasculature in Cav-1
      knockout mice and found a significant increase in BRB permeability, compared with
      wild-type controls, with branch veins being frequent sites of breakdown. Vascular
      hyperpermeability occurred without apparent alteration in junctional proteins.
      Such hyperpermeability was not rescued by inhibiting eNOS activity. Veins of Cav
      1 knockout retinas exhibited additional pathological features, including i) eNOS
      independent enlargement, ii) altered expression of mural cell markers (eg, down
      regulation of NG2 and up-regulation of alphaSMA), and iii) dramatic alterations
      in mural cell phenotype near the optic nerve head. We observed a significant NO
      dependent increase in retinal artery diameter in Cav-1 knockout mice, suggesting
      that Cav-1 plays a role in autoregulation of resistance vessels in the retina.
      These findings implicate Cav-1 in maintaining BRB integrity in retinal
      vasculature and suggest a previously undefined role in the retinal venous system
      and associated mural cells. Our results are relevant to clinically significant
      retinal disorders with vascular pathologies, including diabetic retinopathy,
      uveoretinitis, and primary open-angle glaucoma. 

PMID- 24326259
TI  - Determination of cysteine and glutathione based on the inhibition of the
      dinuclear Cu(II)-catalyzed luminol-H2O2 chemiluminescence reaction.
AB  - The catalyzed luminol chemiluminescent reaction has received a great amount of
      attention because of its high sensitivity and low background signal which make
      the reaction an attractive analytical chemistry tool. The present study,
      introduces the beneficial catalytic effects of dinuclear Cu(II) complex
      [Cu2L2(TAE)]X2, where TAE=tetraacetylethane; L=N,N(')-dibenzylethylenediamine and
      X=ClO4 on the luminol chemiluminescent reaction as a novel probe for the
      determination of glutathione (GSH) and L-cysteine (CySH) in human serum and
      urine. The [Cu2L2(TAE)]X2 has exhibited highly efficient catalytic activity of
      luminol CL as an artificial peroxidase model at pH as low as 7.5 in water in the
      presence of H2O2?GSH and CySH can induce a sharp decrease in CL intensity from
      the [Cu2L2(TAE)]X2-catalyzed luminol system. Under the selected experimental
      conditions, a linear relationship was obtained between the CL intensity and the
      concentrations of GSH and CySH in the range of 1.0*10(-7)-1.0*10(-4) M, with
      detection limits (S/N=3) of 2.7*10(-8) and 6.8*10(-8) M and RSD<4.2% (n=7) for
      GSH and CySH, respectively.

PMID- 24326260
TI  - Optical properties of Nd3+ doped bismuth zinc borate glasses.
AB  - Glasses with compositions of (100-x) (Bi2ZnOB2O6) -x Nd2O3 (where x=0.1, 0.3,
      0.5, 1 and 2 mol%) were prepared by melt quenching method and characterized
      through optical absorption, emission and decay curve measurements. Optical
      absorption spectra have been analyzed using Judd-Ofelt theory. The emission
      spectra exhibit three peaks at 919, 1063 and 1337 nm corresponding to (4)F3/2 to
      (4)I9/2, (4)I11/2 and (4)I13/2 transitions in the near infrared region. The
      emission intensity of the (4)F3/2 to (4)I11/2 transition increases with increase
      of Nd(3+) concentration up to 1 mol% and then concentration quenching is observed
      for 2 mol% of Nd(3+) concentration. The lifetimes for the (4)F3/2 level are found
      to decrease with increase in Nd2O3 concentration in the glasses. The decay curves
      of the glass up to 0.3 mol% of Nd(3+) exhibit single exponential nature and
      thereafter the curves become nonexponential nature (0.5, 1 and 2 mol%). The
      nonexponential curve has been fitted to the Inokuti-Hirayama model to understand
      the nature of energy transfer process.

PMID- 24326261
TI  - Physicochemical properties of liposomes as potential anticancer drugs carriers.
      Interaction of etoposide and cytarabine with the membrane: spectroscopic studies.
AB  - The interactions between etoposide, cytarabine and 1,2-dihexadecanoyl-sn-glycerol
      3-phosphocholine bilayers were studied using differential scanning calorimetry
      (DSC), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic
      resonance (NMR). These techniques have proven to be a very powerful tool in
      studying the structure and dynamics of phospholipid bilayers. In particular, DSC
      can provide information on the phase transition temperature and cooperativity of
      the lipid molecules in the absence and presence of the drug. Vibrational
      spectroscopy is well suited to the study of drug-lipid interactions, since it
      allows for an investigation of the conformation of phospholipid molecules at
      different levels in lipid bilayers and follows structural changes that occur
      during the gel to liquid-crystalline phase transition. NMR supported the
      determination of the main phase transition temperatures (TC) of 1,2
      dihexadecanoyl-sn-glycerol-3-phosphocholine (DPPC). The main phase transition
      temperature (TC) determined by (1)H NMR is comparable with values obtained by DSC
      for all studied liposomes. The location of cytarabine and etoposide in liposomes
      was also determined by NMR. Atomic force microscopy (AFM) images, acquired
      immediately after sample deposition on a mica surface, revealed the spherical
      shape of lipid vesicles. 

PMID- 24326262
TI  - Characterization by combined optical and FT infrared spectra of 3d-transition
      metal ions doped-bismuth silicate glasses and effects of gamma irradiation.
AB  - Optical and infrared absorption spectral measurements were carried out for binary
      bismuth silicate glass and other derived prepared samples with the same
      composition and containing additional 0.2% of one of 3d transition metal oxides.
      The same combined spectroscopic properties were also measured after subjecting
      the prepared glasses to a gamma dose of 8 Mrad. The experimental optical spectra
      reveal strong UV-near visible absorption bands from the base and extended to all
      TMs-doped samples and these specific extended and strong UV-near visible
      absorption bands are related to the contributions of absorption from both trace
      iron (Fe(3+)) ions present as contaminated impurities within the raw materials
      and from absorption of main constituent trivalent bismuth (Bi(3+)) ions. The
      strong UV-near visible absorption bands are observed to suppress any further UV
      bands from TM ions. The studied glasses show obvious resistant to gamma
      irradiation and only small changes are observed upon gamma irradiation. This
      observed shielding behavior is related to the presence of high Bi(3+) ions with
      heavy mass causing the observed stability of the optical absorption. Infrared
      absorption spectra of the studied glasses reveal characteristic vibrational bands
      due to both modes from silicate network and the sharing of Bi-O linkages and the
      presence of TMs in the doping level (0.2%) causes no distinct changes within the
      number or position of the vibrational modes. The presence of high Bi2O3 content
      (70 mol%) appears to cause stability of the structural building units towards
      gamma irradiation as revealed by FTIR measurements.

PMID- 24326263
TI  - Probing the local environment of hybrid materials designed from ionic liquids and
      synthetic clay by Raman spectroscopy.
AB  - Hybrid organic-inorganic material containing Laponite clay and ionic liquids
      forming cations have been prepared and characterized by FT-Raman spectroscopy, X
      ray diffraction, and thermal analysis. The effect of varying the length of the
      alkyl side chain and conformations of cations has been investigated by using
      different ionic liquids based on piperidinium and imidazolium cations. The
      structure of the N,N-butyl-methyl-piperidinium cation and the assignment of its
      vibrational spectrum have been further elucidated by quantum chemistry
      calculations. The X-ray data indicate that the organic cations are intercalated
      parallel to the layers of the clay. Comparison of Raman spectra of pure ionic
      liquids with different anions and the resulting solid hybrid materials in which
      the organic cations have been intercalated into the clay characterizes the local
      environment experienced by the cations in the hybrid materials. The Raman spectra
      of hybrid materials suggest that the local environment of all confined cations,
      in spite of this diversity in properties, resembles the liquid state of ionic
      liquids with a relatively disordered structure. 

PMID- 24326264
TI  - Crystal structure, vibrational studies, optical properties and DFT calculation of
      bis 2-aminobenzothiazolium tetrachloridocuprate.
AB  - The zero dimensional organic-inorganic hybrid compound (C7H7N2S)2CuCl4 was
      synthesized and characterized by X-ray diffraction, infrared absorption, Raman
      spectroscopy scattering and optical transmission measurements. The title compound
      crystallizes in the monoclinic system with P21/c space group. The unit cell
      parameters are a=7.060 (5) A, b=9.748 (5) A, c=14.037 (5) A, beta=98.520 (5)
      degrees  and Z=2. The copper (II) ion has square planar coordination environment
      and the structure is built up from isolated [CuCl4](2)(-) anion surrounded by
      organic cations connected together via N-H?Cl hydrogen bonding. Room temperature
      IR and Raman spectra of the title compound were recorded and analyzed. The
      theoretical geometrical parameters in the ground state have been investigated by
      density functional theory (DFT) with the B3LYP/LanL2DZ level of theory. The
      organic-inorganic hybrid crystal thin film can be easily prepared by spin-coating
      method from the ethanol solution of the (C7H7N2S)2CuCl4 compound and it showed
      characteristic absorptions of Cu-Cl based layered perovskite centered at 288 and
      400 nm.

PMID- 24326265
TI  - Isolation and analysis of membrane lipids and lipid rafts in common carp
      (Cyprinus carpio L.).
AB  - Cell membranes act as an interface between the interior of the cell and the
      exterior environment and facilitate a range of essential functions including cell
      signalling, cell structure, nutrient uptake and protection. It is composed of a
      lipid bilayer with integrated proteins, and the inner leaflet of the lipid
      bilayer comprises of liquid ordered (Lo) and liquid disordered (Ld) domains. Lo
      microdomains, also named as lipid rafts are enriched in cholesterol,
      sphingomyelin and certain types of proteins, which facilitate cell signalling and
      nutrient uptake. Lipid rafts have been extensively researched in mammals and the
      presence of functional lipid rafts was recently demonstrated in goldfish, but
      there is currently very little knowledge about their composition and function in
      fish. Therefore a protocol was established for the analysis of lipid rafts and
      membranous lipids in common carp (Cyprinus carpio L.) tissues. Twelve lipids were
      identified and analysed in the Ld domain of the membrane with the most
      predominant lipids found in all tissues being; triglycerides, cholesterol,
      phosphoethanolamine and phosphatidylcholine. Four lipids were identified in lipid
      rafts in all tissues analysed, triglycerides (33-62%) always found in the highest
      concentration followed by cholesterol (24-32%), phosphatidylcholine and
      sphingomyelin. Isolation of lipid rafts was confirmed by identifying the presence
      of the lipid raft associated protein flotillin, present at higher concentrations
      in the detergent resistant fraction. The data provided here build a lipid library
      of important carp tissues as a baseline for further studies into virus entry,
      protein trafficking or environmental stress analysis. 

PMID- 24326266
TI  - Enhancement of SIV-specific cell mediated immune responses by co-administration
      of soluble PD-1 and Tim-3 as molecular adjuvants in mice.
AB  - The development of an effective T cell based HIV vaccine would need to elicit
      cell mediated immune responses with superior magnitude, breadth, and quality.
      Since blocking the interactions between inhibitory receptors with their
      associated ligands using soluble PD-1 (sPD-1) and soluble Tim-3 (sTim-3) have
      been shown to reverse T cell exhaustion and enhance cell mediated immune
      responses, we tested if co-administration of sPD-1 and sTim-3 with an adenovirus
      vectored SIV vaccine (rAd5-SIV) can enhance cell mediated immune responses. The
      frequency of SIV antigen specific IFN-gamma spot-forming cells and the secretion
      of IFN-gamma and TNF-alpha by splenocytes from rAd5-SIV immunized mice was
      significantly increased when stimulated ex vivo with SIV peptides in the presence
      of sPD-1 or sTim-3 or both sPD-1 and sTim-3. The magnitude of cell mediated
      immune responses elicited by rAd5-SIV was enhanced by co-administration of sPD-1
      and sTim-3. Co-administration of both sPD-1 and sTim-3 induced higher frequency
      of SIV antigen specific IFN-gamma(+) spot-forming cells to poorly immunogenic Vif
      and Tat. The percentage of cell mediated responses for each SIV antigen became
      more balanced, with reduction to Gag but induction to non-structural proteins.
      Furthermore, co-injection of rAd5-sPD1 and rAd5-sTim3 with rAd5-SIV in mice
      enhanced T cell proliferation capability and generated more antigen specific IFN
      gamma(+) CD4(+) and CD8(+) T cells. Our study provided a new approach to enhance
      vaccine induced cell mediated immune responses, which may be applicable to
      improve the efficacy of vaccines against SIV/HIV. 

PMID- 24326267
TI  - Early dynamic fate changes in haemogenic endothelium characterized at the single
      cell level.
AB  - Haematopoietic stem cells (HSCs) are the founding cells of the adult
      haematopoietic system, born during ontogeny from a specialized subset of
      endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic
      transition (EHT). Although recently imaged in real time, the underlying mechanism
      of EHT is still poorly understood. We have generated a Runx1 +23 enhancer
      reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout
      embryonic development. Here we perform functional analysis of over 1,800 and
      transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of
      EHT at the single-cell level. We show that initiation of the haematopoietic
      programme occurs in cells still embedded in the endothelial layer, and is
      accompanied by a previously unrecognized early loss of endothelial potential
      before HSCs emerge. Our data therefore provide important insights on the timeline
      of early haematopoietic commitment. 

PMID- 24326268
TI  - Intranasal immunization with W 80 5EC adjuvanted recombinant RSV rF-ptn enhances
      clearance of respiratory syncytial virus in a mouse model.
AB  - Respiratory Syncytial Virus (RSV) is a ubiquitous virus that infects almost all
      people by age two and is a major source of respiratory illness in infants, the
      elderly and others with compromised immune systems. Currently there is no
      available vaccine. Prior efforts using formalin-inactivated RSV (FI-RSV) were
      associated with enhanced respiratory disease upon viral exposure following
      clinical vaccine trials. Several researchers and pharmaceutical companies have
      utilized vector-associated live attenuated RSV vaccines in pre-clinical and
      clinical studies. Another attractive approach, however, is a subunit vaccine
      which would be easier to produce and quality control. Our group has previously
      demonstrated in a murine model of infection that intranasal immunization with
      nanoemulsion-inactivated and adjuvanted RSV induces humoral and cellular immune
      responses, resulting in protection against RSV infection. The present studies
      characterize the immune responses elicited by intranasal RSV F protein adjuvanted
      with nanoemulsion. Intranasal application of nanoemulsion adjuvanted F protein
      induced a rapid and robust systemic and mucosal antibody response, as well as
      protection against subsequent RSV challenge. Importantly, RSV challenge in
      immunized animals did not elicit airway hyper-reactivity, a Th2-skewed immune
      response or immunopathology associated with hypersensitivity reactions with
      formalin-inactivated vaccine. These results suggest that RSV F protein adjuvanted
      with nanoemulsion may be a good mucosal vaccine candidate. Formulating RSV F
      protein in nanoemulsion creates a well-defined and well-controlled vaccine that
      can be delivered intranasally to induce T cell mediated immunity without inducing
      enhanced disease associated with the mouse model of FI-RSV vaccination and
      infection. 

PMID- 24326270
TI  - What is new in the biology and treatment of pediatric rhabdomyosarcoma?
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight some of the
      advances in the way we think about rhabdomyosarcoma (RMS). Recent outcome and
      biological analyses have shifted the risk stratification and treatment paradigms
      for pediatric RMS. RECENT FINDINGS: The presence or absence of the FOXO1
      translocation is one of the most important prognostic factors in RMS. Future
      clinical studies will incorporate FOXO1 translocation status within risk
      stratification criteria. Molecular analyses have identified RAS/NF1, hedgehog, IL
      4R, and ALK pathway abnormalities as potential therapeutic targets in RMS.
      Reductions in systemic therapy are possible, although radiation therapy remains
      essential to prevent local failures in most patients. SUMMARY: Although survival
      for RMS has not improved in recent years, refinement in risk stratification,
      further understanding of the biological drivers of the disease, and modifications
      in treatment intensity have set the stage for the next generation of studies in
      RMS.

PMID- 24326271
TI  - Influence of gender on clinical outcomes following transcatheter aortic valve
      implantation from the UK transcatheter aortic valve implantation registry and the
      National Institute for Cardiovascular Outcomes Research.
AB  - Gender differences exist in outcomes after percutaneous coronary intervention and
      coronary artery bypass graft surgery but have yet to be fully explored after
      transcatheter aortic valve implantation. We aimed to investigate gender
      differences after transcatheter aortic valve implantation in the UK National
      Institute for Cardiovascular Outcomes Research registry. A retrospective analysis
      was performed of Medtronic CoreValve and Edwards SAPIEN implantation in 1,627
      patients (756 women) from January 2007 to December 2010. Men had more risk
      factors: poor left ventricular systolic function (11.9% vs 5.5%, p <0.001), 3
      vessel disease (19.4% vs 9.2%, p <0.001), previous myocardial infarction (29.5%
      vs 13.0%, p <0.001), peripheral vascular disease (32.4% vs 23.3%, p <0.001), and
      higher logistic EuroSCORE (21.8 +/- 14.2% vs 21.0 +/- 13.4%, p = 0.046). Thirty
      day mortality was 6.3% (confidence interval 4.3% to 7.9%) in women and 7.4% (5.6%
      to 9.2%) in men and at 1 year, 21.9% (18.7% to 25.1%) and 22.4% (19.4% to 25.4%),
      respectively. There was no mortality difference: p = 0.331 by log-rank test;
      hazard ratio for women 0.91 (0.75 to 1.10). Procedural success (96.6% in women vs
      96.4% in men, p = 0.889) and 30-day cerebrovascular event rates (3.8% vs 3.7%, p
      = 0.962) did not differ. Women had more major vascular complications (7.5% vs
      4.2%, p = 0.004) and less moderate or severe postprocedural aortic regurgitation
      (7.5% vs 12.5%, p = 0.001). In conclusion, despite a higher risk profile in men,
      there was no gender-related mortality difference; however, women had more major
      vascular complications and less postprocedural moderate or severe aortic
      regurgitation.

PMID- 24326272
TI  - Non-high-density lipoprotein cholesterol and coronary artery calcium progression
      in a multiethnic US population.
AB  - Non-high-density lipoprotein cholesterol (non-HDLc) is an independent predictor
      of cardiovascular disease risk, with elevated levels signifying an increased risk
      beyond low-density lipoprotein. Previous data have shown inconsistent association
      of lipid subfractions with progression of coronary artery calcium (CAC), a
      surrogate marker of incident cardiovascular disease. We sought to evaluate the
      association between non-HDLc and development (incident) and progression of CAC in
      a cohort of multiethnic asymptomatic subjects. The cohort (n = 5,705) was derived
      from the limited access data set of the Multi-Ethnic Study of Atherosclerosis
      obtained from the National Heart Lung and Blood Institute. Multivariable
      regression analysis was performed to derive the association between non-HDLc and
      incident CAC (n = 2,927) and non-HDLc and progression of CAC (n = 2,778). In the
      population without CAC at baseline, non-HDLc, especially >190 mg/dl, was
      independently associated with incident CAC (relative risk 1.40, 95% confidence
      interval 1.09 to 1.79, p = 0.008) after adjustments with age, gender, race,
      systolic blood pressure, antihypertension medication use, smoking, diabetes,
      lipid-lowering therapy use, follow-up duration, and waist-hip ratio. Similarly,
      among those with CAC at baseline, non-HDLc levels >190 mg/dl were associated with
      significant CAC progression in the overall population (beta 16.4, 95% confidence
      interval -5.63 to 27.2, p = 0.003) after adjustments. In conclusion, non-HDLc
      levels, especially >190 mg/dl, are consistently associated with increased risk of
      CAC progression. Our results suggest that among lipid fractions, non-HDLc may be
      best suited for the prediction of future CAC progression.

PMID- 24326273
TI  - Significance of imbalance in the ratio of serum n-3 to n-6 polyunsaturated fatty
      acids in patients with acute coronary syndrome.
AB  - This study aimed to assess the balance of serum n-3 to n-6 polyunsaturated fatty
      acids (PUFAs) in patients with acute coronary syndrome (ACS). We enrolled 1,119
      patients who were treated and in whom serum PUFA level was evaluated in 5
      divisions of cardiology in a metropolitan area in Japan. Serum levels of PUFAs,
      including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and
      arachidonic acid (AA), were compared between patients with and without ACS. We
      also evaluated the balance of serum n-3 to n-6 PUFAs, including EPA/AA and DHA/AA
      ratios. EPA/AA values were 0.46 +/- 0.32 and 0.50 +/- 0.32 in the ACS and non-ACS
      groups, respectively. DHA/AA values were 0.95 +/- 0.37 and 0.96 +/- 0.41 in the
      ACS and non-ACS groups, respectively. Next, we divided the patients into 3 groups
      based on the tertiles of EPA/AA or tertiles of DHA/AA to determine the
      independent risk factors for ACS. According to multivariate logistic regression
      analysis, the group with the lowest EPA/AA (<=0.33) had a greater probability of
      ACS (odds ratio 3.14, 95% confidence interval 1.16 to 8.49), but this was not
      true for DHA/AA. In conclusion, an imbalance in the ratio of serum EPA to AA, but
      not in the ratio of DHA to AA, was significantly associated with ACS.

PMID- 24326274
TI  - Antecedents to cardiac arrests in a teaching hospital intensive care unit.
AB  - BACKGROUND: In hospital cardiac arrests (CA) treated with cardio-pulmonary
      resuscitation (CPR) outside of the intensive care unit (ICU) have poor outcomes.
      Most are preceded by deranged vital signs. There are, however, limited studies
      assessing antecedents to CAs inside the ICU. OBJECTIVES: To study the antecedents
      to, and characteristics of CAs in ICU. STUDY POPULATION: We prospectively
      identified CA cases that occurred inside our ICU between January 2010 and July
      2012. Controls were obtained by sequentially matching ICU patients based on
      APACHE III diagnosis, APACHE III score, age, gender and length of stay in ICU.
      RESULTS: Thirty-six patients had a CA during the study period (6.28/1000
      admissions). In the 12h prior to CA, index patients had higher maximum (22
      breaths/min vs. 18 breaths/min, p=0.001) and minimum respiratory rates (16
      breaths/min vs. 12 breaths/min, p=0.031), a lower median mean arterial pressure
      (65 mmHg vs. 70 mmHg, p=0.029) and systolic blood pressure (97 mmHg vs. 106 mmHg,
      p=0.033), a higher central venous pressure (14 cm H2O vs. 11 cm H2O, p=0.008) and
      a lower bicarbonate level (20.5 mmol vs. 26 mmol, p=0.018) compared to controls.
      CA patients also had a higher maximum dose of noradrenaline (norepinephrine)
      (17.5 mcg/min vs. 8.0 mcg/min, p=0.052) but there was no difference in any other
      levels of intensive care support. Two-thirds of CA's occurred within the first 48
      h of ICU admission. The initial monitored rhythm was non-shock responsive
      (pulseless electrical activity, bradycardia or asystole) in 26/36 (72%). Return
      of spontaneous circulation was achieved in 29/36 (80.6%) patients, with 16/36
      (44.4%) surviving to hospital discharge. CONCLUSIONS: In the period leading up to
      the CA inside ICU, there were signs of physiological instability and the need for
      higher doses of noradrenaline. Return of spontaneous circulation was achieved in
      80%. However, in-hospital mortality was greater than 50%.

PMID- 24326275
TI  - Synthesis and insecticidal evaluation of novel anthranilic diamides containing N
      substitued nitrophenylpyrazole.
AB  - To cope with developing pest resistance and ecological problems associated with
      conventional insecticides and to search for potent insecticides targeting at
      ryanodine receptor (RyR), a series of novel anthranilic diamides containing N
      substitued nitrophenylpyrazole were designed and synthesized. The insecticidal
      activities of target compounds against oriental armyworm (Mythimna separata) and
      diamondback moth (Plutella xylostella) were evaluated in our greenhouse by bio
      assay tests and the relative structure-activity relationships were briefly
      discussed. Most compounds exhibited moderate to high activities, in which G7 and
      K5 showed high activity against oriental armyworm and K2 and K4 against
      diamondback moth even better than the control-chlorantraniliprole. The calcium
      imaging technique was used to investigate the effects of several typical title
      compounds on the [Ca(2+)](i), especially the effects of G7 on the intracellular
      calcium ion concentration ([Ca(2+)](i)) in neurons, which indicated that some
      title compounds were potent activators of the RyR.

PMID- 24326276
TI  - Comparative molecular field analysis of fenoterol derivatives interacting with an
      agonist-stabilized form of the beta2-adrenergic receptor.
AB  - The beta2-adrenergic receptor (beta2-AR) agonist [(3)H]-(R,R')-methoxyfenoterol
      was employed as the marker ligand in displacement studies measuring the binding
      affinities (Ki values) of the stereoisomers of a series of 4'-methoxyfenoterol
      analogs in which the length of the alkyl substituent at alpha' position was
      varied from 0 to 3 carbon atoms. The binding affinities of the compounds were
      additionally determined using the inverse agonist [(3)H]-CGP-12177 as the marker
      ligand and the ability of the compounds to stimulate cAMP accumulation, measured
      as EC50 values, were determined in HEK293 cells expressing the beta2-AR. The data
      indicate that the highest binding affinities and functional activities were
      produced by methyl and ethyl substituents at the alpha' position. The results
      also indicate that the Ki values obtained using [(3)H]-(R,R')-methoxyfenoterol as
      the marker ligand modeled the EC50 values obtained from cAMP stimulation better
      than the data obtained using [(3)H]-CGP-12177 as the marker ligand. The data from
      this study was combined with data from previous studies and processed using the
      Comparative Molecular Field Analysis approach to produce a CoMFA model reflecting
      the binding to the beta2-AR conformation probed by [(3)H]-(R,R')-4'
      methoxyfenoterol. The CoMFA model of the agonist-stabilized beta2-AR suggests
      that the binding of the fenoterol analogs to an agonist-stabilized conformation
      of the beta2-AR is governed to a greater extend by steric effects than binding to
      the [(3)H]-CGP-12177-stabilized conformation(s) in which electrostatic
      interactions play a more predominate role.

PMID- 24326277
TI  - Design, synthesis and biological evaluation of ezrin inhibitors targeting
      metastatic osteosarcoma.
AB  - Respiratory failure due to pulmonary metastasis is the major cause of death for
      patients with osteosarcoma. However, the molecular basis for metastasis of
      osteosarcoma is poorly understood. Recently, ezrin, a member of the ERM family of
      proteins, has been associated with osteosarcoma metastasis to the lungs. The
      small molecule NSC 668394 was identified to bind to ezrin, inhibit in vitro and
      in vivo cell migration, invasion, and metastatic colony survival. Reported herein
      are the design and synthesis of analogues of NSC 668394, and subsequent
      functional ezrin inhibition studies. The binding affinity was characterized by
      surface plasmon resonance technique. Cell migration and invasion activity was
      determined by electrical cell impedance methodology. Optimization of a series of
      heterocyclic-dione analogues led to the discovery of compounds 21k and 21m as
      potential novel antimetastatic agents. 

PMID- 24326278
TI  - Rational design and synthesis of topoisomerase I and II inhibitors based on
      oleanolic acid moiety for new anti-cancer drugs.
AB  - Semisynthetic reactions were conducted on oleanolic acid, a common plant-derived
      oleanane-type triterpene. Ten rationally designed derivatives of oleanolic acid
      were synthesized based on docking studies and tested for their topoisomerase I
      and IIalpha inhibitory activity. Semisynthetic reactions targeted C-3, C-12, C
      13, and C-17. Nine of the synthesized compounds were identified as new compounds.
      The structures of these compounds were confirmed by spectroscopic methods (1D, 2D
      NMR and MS). Five oleanolic acid analogues (S2, S3, S5, S7 and S9) showed higher
      activity than camptothecin (CPT) in the topoisomerase I DNA relaxation assay.
      Four oleanolic acid analogues (S2, S3, S5 and S6) showed higher activity than
      etoposide in a topoisomerase II assay. The results indicated that the C12-C13
      double bond of the oleanolic acid skeleton is important for the inhibitory
      activity against both types of topoisomerases, while insertion of a longer chain
      at either position 3 or 17 increases the activity against topoisomerases by
      various degrees. Some of the synthesized compounds act as dual inhibitors for
      both topoisomerase I and IIalpha. 

PMID- 24326279
TI  - 7,7'-Diazaindirubin--a small molecule inhibitor of casein kinase 2 in vitro and
      in cells.
AB  - Aza- and diaza-bisindoles were synthesized by coupling of 7-azaisatin, 7
      azaoxindol, 7-azaindoxyl acetate, and their non-aza counterparts, respectively.
      Whereas 7,7'-diazaindigo (10) and 7,7'-diazaisoindigo (11) did not show
      antiproliferative activity in several human tumor cell lines up to 100 MUM, 7
      azaindirubin (12) and 7'-azaindirubin (13) were more active than the parent
      molecule, indirubin, in LXFL529L cells (human large cell lung tumor xenograft),
      and 7,7'-diazaindirubin (14) was exhibiting substantially enhanced growth
      inhibitory activity in these cells. In the NCI 60 cell line panel, 14 displayed
      antiproliferative activity preferentially in certain melanoma and non-small cell
      lung cancer cells. In contrast to the potent serine/threonine/tyrosine kinase
      inhibition observed for indirubins, kinase inhibition profiling of 14 in 220
      kinases revealed largely a loss of kinase inhibitory activity towards most
      kinases, with retained inhibitory activity for just a few kinases. At 1 MUM
      concentration, especially casein kinases CK1gamma3, CK2alpha, CK2alpha2, and SIK
      were inhibited by more than 50%. In cell-based assays, 14 markedly affected CK2
      mediated signaling in various human tumor cells. In MCF7 cells, 14 induced cell
      cycle arrest at G1 and G2/M and apoptosis, whereas CK2-deficient MCF7 cells were
      resistant. These findings reveal a novel key mechanism of action for 14,
      suggesting primarily CK2 inhibition to be causally related to growth inhibition
      of human tumor cells.

PMID- 24326280
TI  - Isolation of antiplasmodial anthraquinones from Kniphofia ensifolia, and
      synthesis and structure-activity relationships of related compounds.
AB  - Bioassay-guided separation of the South African plant Kniphofia ensifolia for
      antiplasmodial activity led to the isolation of two new anthraquinones, named
      kniphofiones A and B (3 and 4), together with three known bioactive anthraquinone
      monomers (1, 2 and 5), and four known bisanthraquinones (6-9). The structures of
      the two new compounds were elucidated based on analyses of their 1D and 2D NMR
      spectra and mass spectrometric data. The dimeric compounds 6 and 7 displayed the
      strongest antiplasmodial activity among all the isolated compounds, with IC50
      values of 0.4 +/- 0.1 and 0.2 +/- 0.1 MUM, respectively. The two new compounds
      displayed modest activities, with IC50 values of 26 +/- 4 and 9 +/- 1 MUM,
      respectively. Due to the synthetic accessibility of the new compounds and the
      increased activity shown by the dimeric compounds, a structure-activity
      relationship study was conducted. As a result, one analogue of kniphofione B (4),
      the caffeic acid derivative of aloe-emodin, was found to have the highest
      activity among all the aloe-emodin derivatives, with an IC50 value of 1.3 +/- 0.2
      MUM.

PMID- 24326281
TI  - Decision aid reduces misperceptions about hormone therapy: a randomized
      controlled trial.
AB  - OBJECTIVE: This study aims to evaluate the role of a decision aid intervention in
      knowledge of menopausal symptom management. METHODS: Five hundred fifteen U.S.
      women who had menopausal symptoms and had discussed symptom management with
      providers within the past 12 months were assigned to either receive a decision
      aid or not. Participants completed a telephone survey 2 weeks after enrollment to
      assess knowledge. Overall knowledge scores and knowledge scores for general
      symptoms, benefits of hormone therapy, and risks of HT were compared between the
      decision aid arm and the control arm. RESULTS: Four hundred one women completed
      the survey. Participants in the decision aid arm had a significantly higher mean
      (SD) knowledge score (63.3% [18.4%]) compared with the control arm (57.5%
      [16.4%]; P = 0.001). Specifically, participants in the decision aid arm had
      significantly higher scores for general symptoms (mean difference, 11.0; 95% CI,
      5.3 to 16.6; P < 0.001) and knowledge about benefits of HT (mean difference, 4.2;
      95% CI, 0.03 to 8.5; P = 0.048) compared with the control arm. However, scores on
      knowledge about HT risks were not different between the arms (mean difference,
      2.1; 95% CI, -3.0 to 7.2; P = 0.422). CONCLUSIONS: The decision aid arm has
      greater knowledge of menopausal symptom management compared with the control arm,
      although the difference is small. In general, there is a considerable lack of
      knowledge about menopausal symptoms and HT risks.

PMID- 24326282
TI  - Are acupuncture and Chinese herbal medicine effective options for hot flashes?

PMID- 24326283
TI  - In reply.

PMID- 24326284
TI  - To pick, choose, or single out.

PMID- 24326285
TI  - Still another selective estrogen receptor modulator to enhance women's health:
      this time in combination with conjugated equine estrogens.

PMID- 24326286
TI  - Factors influencing breeding success, ovarian cyclicity, and cub survival in zoo
      managed tigers (Panthera tigris).
AB  - Understanding factors that influence reproduction and offspring survival in zoo
      populations is critical for management of threatened and endangered species.
      Examination of long-term data (1989-2011) compiled from the Association of Zoos
      and Aquarium's zoo-managed tiger breeding program provides the basis for a more
      thorough understanding of reproduction and scientifically based decisions for
      effective population management in this endangered felid. Biological and
      management-related factors that could influence tiger breeding success and cub
      survival were evaluated using logistic mixed models. Breeding success improved
      with female age until approximately age five, then declined thereafter.
      Experienced female breeders had greater breeding success than inexperienced
      females. Litter size was most predictive of cub survival, with average-sized
      litters (3-4 cubs) experiencing the highest proportional survival. Management
      related factors, such as whether the breeding institution had a recent tiger
      litter and whether both animals were already located at the same institution,
      also influenced breeding success and cub survival. These results highlight the
      importance of institutional husbandry experience and the need to retain knowledge
      through staff turnovers to achieve optimal reproductive success. Using fecal
      estrogen data, frequency of ovarian cyclicity and mean cycle length did not
      differ by female age or parity; thus, lack of cyclicity and/or increased cycle
      duration are not likely explanations for declining breeding success with age.
      These results provide valuable reproductive information that should improve
      scientific management of zoo-based tiger populations. 

PMID- 24326287
TI  - MicroRNA in situ hybridization for formalin fixed kidney tissues.
AB  - In this article we describe a method for colorimetric detection of miRNA in the
      kidney through in situ hybridization with digoxigenin tagged microRNA probes.
      This protocol, originally developed by Kloosterman and colleagues for broad use
      with Exiqon miRNA probes(1), has been modified to overcome challenges inherent in
      miRNA analysis in kidney tissues. These include issues such as structure
      identification and hard to remove residual probe and antibody. Use of relatively
      thin, 5 mm thick, tissue sections allowed for clear visualization of kidney
      structures, while a strong probe signal was retained in cells. Additionally,
      probe concentration and incubation conditions were optimized to facilitate
      visualization of microRNA expression with low background and nonspecific signal.
      Here, the optimized protocol is described, covering the initial tissue collection
      and preparation through the mounting of slides at the end of the procedure. The
      basic components of this protocol can be altered for application to other tissues
      and cell culture models. 

PMID- 24326288
TI  - Immunoglobulin deficiency in patients with Streptococcus pneumoniae or
      Haemophilus influenzae invasive infections.
AB  - OBJECTIVES: Immunoglobulin (Ig) deficiency is a well-known risk factor for
      Streptococcus pneumoniae or Haemophilus influenzae infections and noteworthy
      invasive diseases. However, the proportion of these deficiencies in cases of
      invasive disease is unknown. The objective of this study was to evaluate the rate
      of Ig deficiency in cases of invasive disease. METHODS: A prospective study was
      conducted from January 2008 to October 2010 in two French hospitals. Measurement
      of Ig levels was carried out in patients hospitalized for invasive diseases.
      RESULTS: A total of 119 patients were enrolled in the study, with nine cases of
      H. influenzae and 110 cases of S. pneumoniae invasive disease. There were 18
      cases of meningitis, 79 of invasive pneumonia, and 22 other invasive diseases.
      Forty-five patients (37.8%) had an Ig abnormality, 37 of whom had an Ig
      deficiency (20 IgG <6g/l, four isolated IgA <0.7g/l, and 13 isolated IgM
      <0.5g/l), while eight had an elevated monoclonal paraprotein. Nineteen of these
      45 patients had a clearly defined Ig abnormality, with five primary deficiencies
      (three common variable immunodeficiencies and two complete IgA deficiencies) and
      14 secondary deficiencies, mainly lymphoproliferative disorders. All these
      deficiencies were either not known or not substituted. CONCLUSIONS: Humoral
      deficiency is frequent in patients with S. pneumoniae or H. influenzae invasive
      disease and Ig dosage should be proposed systematically after such infections.

PMID- 24326290
TI  - Protein microarray technology: how far off is routine diagnostics?
AB  - The nature of protein microarray platforms is favorable for multiplexing, leading
      to the development of tools for personalised medicine and highly precise
      diagnostics. However, to date, only a limited number of protein microarrays are
      available in the in vitro diagnostics (IVD) market. This review article will
      focus on the following operational challenges that are crucial for the use of
      microarrays in clinical settings: (1) probe printing and quality control; (2)
      procurement of bio-reagents and antibody cross-reactivity; (3) mass transport
      limitations and assay automation; (4) calibration and quantification. A selection
      of microarray assays applicable to IVD and a summary of the diagnostic products
      currently available on the market are provided. 

PMID- 24326289
TI  - Impact of the International Nosocomial Infection Control Consortium (INICC)
      multidimensional hand hygiene approach in three cities of Colombia.
AB  - OBJECTIVE: To assess the feasibility and effectiveness of the International
      Nosocomial Infection Control Consortium (INICC) multidimensional hand hygiene
      (HH) approach in Colombia, and analyze predictors of poor HH compliance. METHODS:
      An observational, prospective, interventional, before-and-after study was
      conducted from May 2003 through September 2010 in 10 intensive care units (ICUs)
      of six hospitals in three cities. The study was divided into two periods: a
      baseline and a follow-up period. Observations for HH compliance were done in each
      ICU during randomly selected 30-min periods. The multidimensional HH approach
      included: (1) administrative support, (2) supplies availability, (3) education
      and training, (4) reminders in the workplace, (5) process surveillance, and (6)
      performance feedback. RESULTS: A total of 13 187 opportunities for HH were
      observed. Overall HH compliance increased from 50% to 77% (relative risk 1.55,
      95% confidence interval 1.43-1.68; p=0.0001). Multivariate and univariate
      analyses showed that several variables were significantly associated with poor HH
      compliance: males vs. females (67% vs. 77%; p=0.0001), physicians vs. nurses (59%
      vs. 78%; p<0.0001), and adult vs. pediatric ICUs (76% vs. 42%; p<0.001), among
      others. CONCLUSIONS: Adherence to HH was increased by 55% with the INICC
      approach. Programs targeted at improving HH in variables found to be predictors
      of poor compliance should be implemented.

PMID- 24326291
TI  - Two genomic regions together cause dark abdominal pigmentation in Drosophila
      tenebrosa.
AB  - Pigmentation is a rapidly evolving trait that is under both natural and sexual
      selection in many organisms. In the quinaria group of Drosophila, nearly all of
      the 30 species have an abdomen that is light in color with distinct markings; D.
      tenebrosa is the exception in that it has a completely melanic abdomen with no
      visible markings. In this study, we use a combination of quantitative genetic and
      candidate gene approaches to investigate the genetic basis of abdominal
      pigmentation in D. tenebrosa. We find that abdominal pigmentation is invariant
      across wild-caught lines of D. tenebrosa and is not sexually dimorphic.
      Quantitative genetic mapping utilizing crosses between D. tenebrosa and the light
      colored D. suboccidentalis indicates that two genomic regions together underlie
      abdominal pigmentation, including the X-chromosome and an autosome (Muller
      Element C/E). Further support for their central importance in pigmentation is
      that experimental introgression of one phenotype into the other species, in
      either direction, results in introgression of these two genomic regions. Finally,
      the expression of the X-linked gene yellow in the pupae exactly foreshadows the
      adult melanization pattern in the abdomen of both species, suggesting that
      changes in the regulation of yellow are important for the phenotypic divergence
      of D. tenebrosa from the rest of the quinaria group. These results contribute to
      a body of work that demonstrates how changes in expression of highly conserved
      genes can cause substantial phenotypic differences even between closely related
      species. 

PMID- 24326292
TI  - Cross-validation in association mapping and its relevance for the estimation of
      QTL parameters of complex traits.
AB  - Association mapping has become a widely applied genomic approach to identify
      quantitative trait loci (QTL) and dissect the genetic architecture of complex
      traits. However, approaches to assess the quality of the obtained QTL results are
      lacking. We therefore evaluated the potential of cross-validation in association
      mapping based on a large sugar beet data set. Our results show that the
      proportion of the population that should be used as estimation and validation
      sets, respectively, depends on the size of the mapping population. Generally, a
      fivefold cross-validation, that is, 20% of the lines as independent validation
      set, appears appropriate for commonly used population sizes. The predictive power
      for the proportion of genotypic variance explained by QTL was overestimated by on
      average 38% indicating a strong bias in the estimated QTL effects. The cross
      validated predictive power ranged between 4 and 50%, which are more realistic
      estimates of this parameter for complex traits. In addition, QTL frequency
      distributions can be used to assess the precision of QTL position estimates and
      the robustness of the detected QTL. In summary, cross-validation can be a
      valuable tool to assess the quality of QTL parameters in association mapping. 

PMID- 24326293
TI  - Genetic diversity and classification of Oryza sativa with emphasis on Chinese
      rice germplasm.
AB  - Despite extensive studies on cultivated rice, the genetic structure and
      subdivision of this crop remain unclear at both global and local scales. Using 84
      nuclear simple sequence repeat markers, we genotyped a panel of 153 global rice
      cultivars covering all previously recognized groups and 826 cultivars
      representing the diversity of Chinese rice germplasm. On the basis of model-based
      grouping, neighbour-joining tree and principal coordinate analysis, we confirmed
      the widely accepted five major groups of rice cultivars (indica, aus, aromatic,
      temperate japonica and tropical japonica), and demonstrated that rayada rice was
      unique in genealogy and should be treated as a new (the sixth) major group of
      rice germplasm. With reference to the global classification of rice cultivars, we
      identified three major groups (indica, temperate japonica and tropical japonica)
      in Chinese rice germplasm and showed that Chinese temperate japonica contained
      higher diversity than that of global samples, whereas Chinese indica and tropical
      japonica maintained slightly lower diversity than that present in the global
      samples. Particularly, we observed that all seasonal, drought-tolerant and
      endosperm types occurred within each of three major groups of Chinese cultivars,
      which does not support previous claims that seasonal differentiation exists in
      Indica and drought-tolerant differentiation is present in Japonica. It is most
      likely that differentiation of cultivar types arose multiple times stemming from
      artificial selection for adaptation to local environments. 

PMID- 24326294
TI  - Fatal pulmonary disease and encephalic complication in a man with HSV-1
      Infection: a case report.
AB  - Herpes simplex virus type 1 (HSV-1) is associated with a large spectrum of
      pathologies i.e. pulmonary diseases. Although it has often been isolated from the
      lower respiratory tract of immunocompetent or immunosuppressed patients
      undergoing prolonged mechanical ventilation (MV), its causative role in serious
      lung infections is still unclear. Here we report the case of a 44-year-old man
      presenting seizures that followed an acute respiratory illness that occurred
      during hospitalization. The detection of HSV-1 DNA in bronchoalveolar lavage
      (BAL), in spinal fluid, and in blood samples, supported the evidence of a
      disseminated viral infection that strengthens the hypothesis of herpetic
      pneumonia as a possible triggering cause of neurological complications and fatal
      outcome. This observation draws attention to the opportunity of introducing tests
      for the detection of HSV-1 into the diagnostic protocols for such patients. In
      fact, adequate diagnostic tools would favor early diagnosis and correct therapy
      to HSV-1 that could reduce the possibility of either encephalic complications or
      the rate of mortality in critical long-term patients affected by respiratory
      pathologies who need assisted ventilation. 

PMID- 24326295
TI  - Increased O-GlcNAcylation reduces pathological tau without affecting its normal
      phosphorylation in a mouse model of tauopathy.
AB  - Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of
      hyperphosphorylated tau, are a defining pathological feature of Alzheimer's
      Disease and other tauopathies. Progressive accumulation of tau into NFT is
      considered to be a toxic cellular event causing neurodegeneration. Tau is subject
      to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of
      tau has been suggested to regulate tau phosphorylation. We tested if an increase
      in tau O-GlcNAcylation affected tau phosphorylation and aggregation in the
      rTg4510 tau transgenic mouse model. Acute treatment of rTg4510 mice with an O
      GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes
      implicated in tau pathology. More importantly, long-term inhibitor treatment
      strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons,
      and protected against the formation of pathological tau species without altering
      the phosphorylation of non-pathological tau. This indicates that O-GlcNAcylation
      prevents the aggregation of tau in a manner that does not affect its normal
      phosphorylation state. Collectively, our results support O-GlcNAcase inhibition
      as a potential therapeutic strategy for the treatment of Alzheimer's Disease and
      other tauopathies. 

PMID- 24326296
TI  - Tuning gap states at organic-metal interfaces via quantum size effects.
AB  - Organic-metal interfaces are key elements in organic-based electronics. The
      energy-level alignment between the metal Fermi level and the molecular orbital
      levels determines the injection barriers for the charge carriers at the
      interfaces, which are crucial for the performance of organic electronic devices.
      Dipole formation at the interfaces has been regarded as the main factor that
      affects the energy-level alignment. Several models have been proposed for the
      mechanism of dipole formation in the context of the interface between organic
      molecules and a bulk metal crystal surface, at which surface states were mostly
      used to probe the interfacial properties. Here we report that when the bulk metal
      crystal is replaced by a uniform metal thin film, the resulting two-dimensional
      quantum-well states will be able to not only probe but also modify the
      interfacial electronic structures, such as gap states, that have no counterpart
      at the organic-bulk crystal interface. 

PMID- 24326297
TI  - A facile method to align carbon nanotubes on polymeric membrane substrate.
AB  - The alignment of carbon nanotubes (CNT) is the fundamental requirement to ensure
      their excellent functions but seems to be desolated in recent years. A facile
      method, hot-press combined with peel-off (HPPO), is introduced here, through
      which CNT can be successfully vertically aligned on the polymeric membrane
      substrate. Shear force and mechanical stretch are proposed to be the main forces
      to align the tubes perpendicular to the substrate surface during the peel-off
      process. The alignment of CNT keeps its orientation in a thin hybrid membrane by
      dip-coating cellulose acetate dope solution. It is expected that the stable
      alignment of CNT by HPPO would contribute to the realization of its potential
      applications. 

PMID- 24326298
TI  - Handedness differences in information framing.
AB  - Previous research has shown that strength of handedness predicts differences in
      sensory illusions, Stroop interference, episodic memory, and beliefs about body
      image. Recent evidence also suggests handedness differences in the susceptibility
      to common decision biases such as anchoring and sunk cost. The present paper
      extends this line of work to attribute framing effects. Sixty-three
      undergraduates were asked to advise a friend concerning the use of a safe allergy
      medication during pregnancy. A third of the participants received negatively
      framed information concerning the fetal risk of the drug (1-3% chance of having a
      malformed child); another third received positively-framed information (97-99%
      chance of having a normal child); and the final third received no counseling
      information and served as the control. Results indicated that, as predicted,
      inconsistent (mixed)-handers were more responsive than consistent (strong)
      handers to information changes and readily update their beliefs. Although not
      significant, the data also suggested that only inconsistent handers were affected
      by information framing. Theoretical implications as well as ongoing work in
      holistic versus analytic processing, contextual sensitivity, and brain asymmetry
      will be discussed. 

PMID- 24326299
TI  - Special issues on advances in quantitative genetics: introduction.

PMID- 24326300
TI  - Universal coverage challenges require health system approaches; the case of
      India.
AB  - This paper uses the case of India to demonstrate that Universal Health Coverage
      (UHC) is about not only health financing; personal and population services
      production issues, stewardship of the health system and generation of the
      necessary resources and inputs need to accompany the health financing proposals.
      In order to help policy makers address UHC in India and sort out implementation
      issues, the framework developed by the World Health Organization (WHO) in the
      World Health Report 2000 and its subsequent extensions are advocated. The
      framework includes final goals, generic intermediate objectives and four inter
      dependent functions which interact as a system; it can be useful by diagnosing
      current shortcomings and facilitating the filling up of gaps between functions
      and goals. Different positions are being defended in India re the preconditions
      for UHC to succeed. This paper argues that more (public) money will be important,
      but not enough; it needs to be supplemented with broad interventions at various
      health system levels. The paper analyzes some of the most important issues in
      relation to the functions of service production, generation of inputs and the
      necessary stewardship. It also pays attention to reform implementation, as
      different from its design, and suggests critical aspects emanating from a review
      of recent health system reforms. Precisely because of the lack of comparative
      reference for India, emphasis is made on the need to accompany implementation
      with analysis, so that the "solutions" ("what to do?", "how to do it?") are found
      through policy analysis and research embedded into flexible implementation.
      Strengthening "evidence-to-policy" links and the intelligence dimension of
      stewardship/leadership as well as accountability during implementation are
      considered paramount. Countries facing similar challenges to those faced by India
      can also benefit from the above approaches. 

PMID- 24326301
TI  - Analyzing protein dynamics using hydrogen exchange mass spectrometry.
AB  - All cellular processes depend on the functionality of proteins. Although the
      functionality of a given protein is the direct consequence of its unique amino
      acid sequence, it is only realized by the folding of the polypeptide chain into a
      single defined three-dimensional arrangement or more commonly into an ensemble of
      interconverting conformations. Investigating the connection between protein
      conformation and its function is therefore essential for a complete understanding
      of how proteins are able to fulfill their great variety of tasks. One possibility
      to study conformational changes a protein undergoes while progressing through its
      functional cycle is hydrogen-(1)H/(2)H-exchange in combination with high
      resolution mass spectrometry (HX-MS). HX-MS is a versatile and robust method that
      adds a new dimension to structural information obtained by e.g. crystallography.
      It is used to study protein folding and unfolding, binding of small molecule
      ligands, protein-protein interactions, conformational changes linked to enzyme
      catalysis, and allostery. In addition, HX-MS is often used when the amount of
      protein is very limited or crystallization of the protein is not feasible. Here
      we provide a general protocol for studying protein dynamics with HX-MS and
      describe as an example how to reveal the interaction interface of two proteins in
      a complex.

PMID- 24326302
TI  - The hcp to fcc transformation path of scandium trihydride under high pressure.
AB  - We used density functional theory to calculate the phase stability of the hcp
      (hexagonal close packed) and the fcc (face centered cubic) structures of ScH3.
      The hcp form is stable up to 22 GPa according to the generalized gradient
      approximation calculation. Then the fcc form becomes energetically more stable.
      In order to provide insight into the phase transition mechanism, we modeled the
      hcp to fcc transition by sliding the hcp basal planes, i.e. (001)h planes, in
      such a way that the ABABAB sequence of the hcp form is altered into the ABCABC
      sequence of the fcc form. This sliding was suggested by the experiment. The
      configurations of these sliding steps are our proposed intermediate
      configurations, whose symmetry group is the Cm group. By using the Cm
      crystallography, we can match the d-spacings from the lattice planes of the hcp
      and fcc forms and the intermediate planes measured from the experiment. We also
      calculated the enthalpy per step, from which the energy barrier between the two
      phases at various pressures was derived. The barrier at 35 GPa is 0.370 eV per
      formula or 0.093 eV/atom. The movements of the hydrogen atoms during the hcp to
      intermediate phase transition are consistent with the result from the Raman
      spectra.

PMID- 24326303
TI  - High yield and high specific activity synthesis of [18F]fallypride in a batch
      microfluidic reactor for micro-PET imaging.
AB  - [(18)F]fallypride was synthesized in a batch microfluidic chip with a
      radiochemical yield of 65 +/- 6% (n = 7) and an average specific activity of 730
      GBq MUmol(-1) (20 Ci MUmol(-1)) (n = 4). Specific activity was ~2-fold higher
      than [(18)F]fallypride synthesized in a macroscale radiosynthesizer, despite
      starting with significantly less radioactivity, and thus safer conditions, in the
      microchip.

PMID- 24326305
TI  - A small molecule that displays marked reactivity toward copper- versus zinc
      amyloid-beta implicated in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex, multifactorial, neurodegenerative disease
      that poses tremendous difficulties in pinpointing its precise etiology. A
      toolkit, which specifically targets and modulates suggested key players, may
      elucidate their roles in disease onset and progression. We report high-resolution
      insights on the activity of a small molecule (L2-NO) which exhibits reactivity
      toward Cu(II)-amyloid-beta (Abeta) over Zn(II)-Abeta.

PMID- 24326304
TI  - The impact of age on the prognostic capacity of CD8+ T-cell activation during
      suppressive antiretroviral therapy.
AB  - OBJECTIVE: To assess whether CD8 T-cell activation predicts risk of AIDS and non
      AIDS morbidity during suppressive antiretroviral treatment (ART). DESIGN: Post
      hoc analyses of ART-naive participants in prospective ART studies. Participants
      with HIV-RNA levels 200 copies/ml or less and CD8 T-cell activation data
      (%CD38HLA-DR) at year-1 of ART were selected to determine years 2-5 incidence of
      AIDS and non-AIDS events. METHODS: We censored data at time of ART interruption
      or virologic failure. Inverse probability of censoring-weighted logistic
      regression was used to correct for informative censoring. RESULTS: We included
      1025 participants; 82% were men, median age 38 years, pre-ART CD4 cell count 255
      cells/MUl, and year-1-activated CD8 T cells 24%. Of these, 752 had 5 years of
      follow-up; 379 remained on ART and had no confirmed plasma HIV-RNA more than 200
      copies/ml. The overall probability of an AIDS or non-AIDS event in years 2-5 was
      estimated at 13% [95% confidence interval (CI) 10-15%] had everyone remained on
      suppressive ART. Higher year-1-activated CD8 T-cell percentage increased the
      probability of subsequent events [odds ratio 1.22 per 10% higher (95% CI 1.04
      1.44)]; this effect was not significant after adjusting for age. Among those age
      50 years at least (n=108 at year 1), the probability of an event in years 2-5 was
      37% and the effect of CD8 T-cell activation was more apparent (odds ratio=1.42,
      P=0.02 unadjusted and adjusted for age). CONCLUSION: CD8 T-cell activation is
      prognostic of clinical events during suppressive ART, although this association
      is confounded by age. The consequences of HIV-associated immune activation may be
      more important in patients 50 years and older.

PMID- 24326306
TI  - The redox series [Ru(bpy)2(L)]n, n = +3, +2, +1, 0, with L = bipyridine, "click"
      derived pyridyl-triazole or bis-triazole: a combined structural, electrochemical,
      spectroelectrochemical and DFT investigation.
AB  - The compounds [Ru(bpy)2(L(1))](ClO4)2 (1(ClO4)2), [Ru(bpy)2(L(2))](ClO4)2
      (2(ClO4)2), [Ru(bpy)2(L(3))](ClO4)2 (3(ClO4)2), [Ru(bpy)2(L(4))](ClO4)2
      (4(ClO4)2), [Ru(bpy)2(L(5))](ClO4)2 (5(ClO4)2), and [Ru(bpy)2(L(6))](ClO4)2
      6(ClO4)2 (bpy = 2,2'-bipyridine, L(1) = 1-(4-isopropyl-phenyl)-4-(2-pyridyl)
      1,2,3-triazole, L(2) = 1-(4-butoxy-phenyl)-4-(2-pyridyl)-1,2,3-triazole, L(3) = 1
      (2-trifluoromethyl-phenyl)-4-(2-pyridyl)-1,2,3-triazole, L(4) = 4,4'-bis-{1-(2,6
      diisopropyl-phenyl)}-1,2,3-triazole, L(5) = 4,4'-bis-{(1-phenyl)}-1,2,3-triazole,
      L(6) = 4,4'-bis-{1-(2-trifluoromethyl-phenyl)}-1,2,3-triazole) were synthesized
      from [Ru(bpy)2(EtOH)2](ClO4)2 and the corresponding "click"-derived pyridyl
      triazole or bis-triazole ligands, and characterized by (1)H-NMR spectroscopy,
      elemental analysis, mass spectrometry and X-ray crystallography. Structural
      analysis showed a distorted octahedral coordination environment about the Ru(II)
      centers, and shorter Ru-N(triazole) bond distances compared to Ru-N(pyridine)
      distances in complexes of mixed-donor ligands. All the complexes were subjected
      to cyclic voltammetric studies, and the results were compared to the well-known
      [Ru(bpy)3](2+) compound. The oxidation and reduction potentials were found to be
      largely uninfluenced by ligand changes, with all the investigated complexes
      showing their oxidation and reduction steps at rather similar potentials. A
      combined UV-vis-NIR and EPR spectroelectrochemical investigation, together with
      DFT calculations, was used to determine the site of electron transfer in these
      complexes. These results provided insights into their electronic structures in
      the various investigated redox states, showed subtle differences in the
      spectroscopic signatures of these complexes despite their similar electrochemical
      properties, and provided clues to the unperturbed redox potentials in these
      complexes with respect to ligand substitutions. The reduced forms of the
      complexes display structured absorption bands in the NIR region. Additionally, we
      also present new synthetic routes for the ligands presented here using Cu
      abnormal carbene catalysts.

PMID- 24326308
TI  - Infant feeding attitudes and breastfeeding intentions of black college students.
AB  - Breastfeeding rates are lowest among Black women than women of other races. An
      understanding of infant feeding attitudes may help improve breastfeeding rates
      among Black women. The theory of planned behavior guided this study to explore
      infant feeding attitudes of Black college students and the contribution of
      attitudes to breastfeeding intentions after controlling for age, gender, income,
      and education level. A sample of 348 Black college students below 45 years old
      with no children and no history of pregnancies were recruited for this study. The
      Iowa Infant Feeding Attitude Scale and a Demographic Questionnaire were used to
      collect data. Participants agreed that breast milk is the ideal food for infants
      and 48% indicated high probability of breastfeeding intentions. Infant feeding
      attitudes also explained approximately 30% (Nagelkerke R (2)) of the variance in
      breastfeeding intentions. Therefore, breastfeeding interventions targeting Black
      women should focus on improving breastfeeding attitudes. 

PMID- 24326307
TI  - Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination.
AB  - Although mammalian long non-coding (lnc)RNAs are best known for modulating
      transcription, their post-transcriptional influence on mRNA splicing, stability
      and translation is emerging. Here we report a post-translational function for the
      lncRNA HOTAIR as an inducer of ubiquitin-mediated proteolysis. HOTAIR associates
      with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well
      as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In
      this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and
      Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation.
      HOTAIR levels are highly upregulated in senescent cells, causing rapid decay of
      targets Ataxin-1 and Snurportin-1, and preventing premature senescence. These
      results uncover a role for a lncRNA, HOTAIR, as a platform for protein
      ubiquitination. 

PMID- 24326309
TI  - Understanding of advance care planning by family members of persons undergoing
      hemodialysis.
AB  - The purpose of this qualitative descriptive study was to explore hemodialysis
      patients' family members' understanding of end-of-life decision-making processes.
      The project aimed to address (a) family members' constructions of advance care
      planning (ACP), including their roles and responsibilities, and (b) family
      members' perceptions of health care providers' roles and responsibilities in ACP.
      Eighteen family members of persons undergoing hemodialysis were recruited
      primarily from outpatient dialysis facilities and interviewed individually.
      Confirmed transcript data were analyzed, coded, and compared, and categories were
      established. Interpretations were validated throughout the interviews and peer
      debriefing sessions were used at a later stage in the analysis. The overarching
      construct identified was one of Protection. Family members protect patients by
      (a) Sharing Burdens, (b) Normalizing Life, and (c) Personalizing Care.
      Recommendations for future research include the need to explore ACP of persons
      undergoing hemodialysis who do not have a family support system. 

PMID- 24326310
TI  - Structure determines medication errors in nursing units: a mechanistic approach.
AB  - Medication errors have long been considered critical in global health care
      systems. However, few studies have been conducted to explore the effects of
      nursing unit structure on medication errors. The purpose of this study,
      therefore, was to determine the effects of structural factors on medication
      errors in nursing units. A total of 977 staff nurses and 62 head nurses
      participated in this cross-sectional design study. The findings show that
      professional autonomy (beta = .53, t = 6.03, p < .01), technology (beta = .25, t
      = 3.02, p < .01), and nursing experts (beta = .52, t = 5.99, p < .01) are
      predictors of medication error rates. This study shows that the structural
      factors influence medication administration and the mechanistic approach is
      specifically in relation of low medication error rates. The author suggests that
      head nurses should consider strategies that require adjustments to unit control
      mechanisms. 

PMID- 24326311
TI  - Revisiting the (7)Li(p,n)(7)Be reaction near threshold.
AB  - In this work we review all the available experimental neutron data for the
      (7)Li(p,n) reaction near threshold which is necessary to obtain an accurate
      source model for Monte Carlo simulations in Boron Neutron Capture Therapy.
      Scattered published experimental results such as cross sections, differential
      neutron yields and total yields were collected and analyzed, exploring the
      sensitivity of the fitting parameters to the different possible variables and
      deriving a consistent working set of parameters to evaluate the neutron source
      near threshold. 

PMID- 24326312
TI  - Glioblastoma, brain metastases and soft tissue sarcoma of extremities: candidate
      tumors for BNCT.
AB  - (10)B-concentration ratios between human glioblastoma multiforme (U87MG), sarcoma
      (S3) and melanoma (MV3) xenografted in nu/nu mice and selected normal tissues
      were investigated to test for preferential (10)B-accumulation. Animals received
      BSH, BPA or both compounds sequentially. Mean (10)B-concentration ratios between
      tumor and normal tissues above 2 were found indicating therapeutic ratios. In
      addition to glioblastoma, brain metastases and soft tissue sarcoma appear to be
      promising targets for future BNCT research. 

PMID- 24326313
TI  - Precise test of internal-conversion theory: transitions measured in five nuclei
      spanning 50<=Z<=78.
AB  - In a research program aimed at testing calculated internal-conversion
      coefficients (ICCs), we have made precise measurements of alphaK values for
      transitions in five nuclei, (197)Pt, (193)Ir, (137)Ba, (134)Cs and (119)Sn, which
      span a wide range of A and Z values. In all cases, the results strongly favor
      calculations in which the final-state electron wave function has been computed
      using a potential that includes the atomic vacancy created by the internal
      conversion process. 

PMID- 24326314
TI  - Digital pulse processing and optimization of the front-end electronics for
      nuclear instrumentation.
AB  - This article describes an algorithm developed for the digital processing of
      signals provided by a high-efficiency well-type NaI(Tl) detector used to apply
      the 4pigamma technique. In order to achieve a low-energy threshold, a new front
      end electronics has been specifically designed to optimize the coupling to an
      analog-to-digital converter (14 bit, 125 MHz) connected to a digital development
      kit produced by Altera((r)). The digital pulse processing is based on an IIR
      (Infinite Impulse Response) approximation of the Gaussian filter (and its
      derivatives) that can be applied to the real-time processing of digitized
      signals. Based on measurements obtained with the photon emissions generated by an
      (241)Am source, the energy threshold is estimated to be equal to ~2 keV
      corresponding to the physical threshold of the NaI(Tl) detector. An algorithm
      developed for a Silicon Drift Detector used for low-energy x-ray spectrometry is
      also described. In that case, the digital pulse processing is specifically
      designed for signals provided by a reset-type preamplifier ((55)Fe source).

PMID- 24326315
TI  - Long-term performances of the 95ZR/95Nb chronometer for nuclear events dating.
AB  - The present work reports on a long-term analysis of the performances of the
      (95)Zr/(95)Nb chronometer for dating a nuclear event. Taking benefit of a recent
      Profiency Test Exercise, a sample containing a standardized mixture of fission
      products has been measured repeatedly with a low background HPGe spectrometer
      during a period extending up to one year with the aim of assessing the accuracy
      of the various zero-time determinations. Evaluation of the uncertainties
      associated to these evaluations was performed using a Monte Carlo approach. Input
      parameters sensitivity has been investigated, especially the influence of the
      (95m)Nb decay branch. The (95)Zr/(95)Nb chronometer was found to be accurate for
      zero-time determination within one day and one week for a decay of 3 months and
      10 months respectively. Sub-day uncertainties are achievable for a two months old
      sample whereas sub-week uncertainties are reached after a decay of six months.
      Limitations of the technique for dating a real event are investigated. 

PMID- 24326316
TI  - Coincidence summing corrections for volume samples using the PENELOPE/penEasy
      Monte Carlo code.
AB  - The coincidence summing correction factors estimated with penEasy, a steering
      program for the Monte Carlo simulation code PENELOPE, and with penEasy-eXtended,
      an in-house modified version of penEasy, are presented and discussed for (152)Eu
      and (134)Cs in volume sources. The geometries and experimental data were obtained
      from an intercomparison study organized by the International Committee for
      Radionuclide Metrology (ICRM). A significant improvement in the results
      calculated with PENELOPE/penEasy was obtained when X-rays are included in the
      (152)Eu simulations. 

PMID- 24326317
TI  - Efficiency calibration of BEGe and extended range detectors.
AB  - Any approach to efficiency calibration of HPGe detectors sensitive to low-energy
      gamma-rays and X-rays has to deal with true coincidence summing. We developed a
      method based on the integration of the EFFTRAN code into the commercial Genie2KTM
      gamma-ray spectrometry software. EFFTRAN's role is to compute true coincidence
      summing corrections and to obtain satisfactory results for detectors sensitive to
      X-rays. EFFTRAN had to be upgraded to include a full simulation of the emission
      of X-rays. In this manner, efficiency calibrations were successfully set up for
      BeGe and XtRa detectors. 

PMID- 24326318
TI  - Real-time in vivo uric acid biosensor system for biophysical monitoring of birds.
AB  - Research on birds has long played an important role in ecological investigations,
      as birds are relatively easily observed, and their high metabolic rates and
      diurnal habits make them quite evidently responsive to changes in their
      environments. A mechanistic understanding of such avian responses requires a
      better understanding of how variation in physiological state conditions avian
      behavior and integrates the effects of recent environmental changes. There is a
      great need for sensor systems that will allow free-flying birds to interact with
      their environment and make unconstrained decisions about their spatial location
      at the same time that their physiological state is being monitored in real time.
      We have developed a miniature needle-based enzymatic sensor system suitable for
      continuous real-time amperometric monitoring of uric acid levels in unconstrained
      live birds. The sensor system was constructed with Pt/Ir wire and Ag/AgCl paste.
      Uricase enzyme was immobilized on a 0.7 mm sensing cavity of Nafion/cellulose
      inner membrane to minimize the influences of background interferents. The sensor
      response was linear from 0.05 to 0.6 mM uric acid, which spans the normal
      physiological range for most avian species. We developed a two-electrode
      potentiostat system that drives the biosensor, reads the output current, and
      wirelessly transmits the data. In addition to extensive characterization of the
      sensor and system, we also demonstrate autonomous operation of the system by
      collecting in vivo extracellular uric acid measurements on a domestic chicken.
      The results confirm our needle-type sensor system's potential for real-time
      monitoring of birds' physiological state. Successful application of the sensor in
      migratory birds could open up a new era of studying both the physiological
      preparation for migration and the consequences of sustained avian flight. 

PMID- 24326319
TI  - The legacy of Marc Jeannerod.

PMID- 24326320
TI  - Neural mass modeling for predicting seizures.

PMID- 24326321
TI  - Association of C-reactive protein levels with fasting and postload glucose levels
      according to glucose tolerance status.
AB  - BACKGROUND AND AIMS: Several studies show that high serum C-reactive protein
      (CRP) levels are associated with an increased risk of diabetes, data that
      strongly supports a possible role for inflammation in diabetogenesis. The aim of
      this study was to determine whether elevated CRP levels are associated with
      fasting plasma glucose (FPG) and/or postload glucose levels according to the
      glucose tolerance status. METHODS: A total of 169 healthy males and non-pregnant
      females aged 18-65 years were enrolled in a population-based cross-sectional
      study. Individuals were allocated into groups with a new diagnosis of normal
      glucose tolerance (NGT) (n = 82), impaired fasting glucose (IFG) (n = 54), and
      impaired glucose tolerance (IGT) (n = 33). Elevated CRP was defined by CRP levels
      >3.0 and <10.0 mg/L, IFG by FPG >=100 and <126 mg/dL, and IGT by plasma glucose
      concentration 2 h postload >=140 and <200 mg/dL. A multiple regression linear
      analysis adjusted by body mass index, waist circumference, and lipid profile was
      performed to evaluate the association between CRP levels (independent variable)
      with FPG and 2 h postload glucose levels (dependent variables). RESULTS:
      Multivariate linear regression analysis showed a significant association between
      hsCRP levels with FPG (beta = 0.536; 95% CI 1.03-5.1, p = 0.005) and 2 h postload
      glucose (beta = 0.209; 95% CI 1.31-2.97, p = 0.01) in the IGT group, but not with
      FPG (beta = 0.147; 95% CI 0.55-2.0, p = 0.25) and 2 h postload glucose (beta =
      0.151; 95% CI 0.83-3.2, p = 0.24) in the IFG group. CONCLUSIONS: Elevated CRP
      levels are associated with FPG and 2 h postload glucose in the individuals with
      IGT, but not in subjects with IFG or NGT.

PMID- 24326322
TI  - Innate immune system cells in atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease of the arterial wall
      characterized by innate and adaptive immune system involvement. A key component
      of atherosclerotic plaque inflammation is the persistence of different innate
      immune cell types including mast cells, neutrophils, natural killer cells,
      monocytes, macrophages and dendritic cells. Several endogenous signals such as
      oxidized low-density lipoproteins, and exogenous signals such as
      lipopolysaccharides, trigger the activation of these cells. In particular, these
      signals orchestrate the early and late inflammatory responses through the
      secretion of pro-inflammatory cytokines and contribute to plaque evolution
      through the formation of foam cells, among other events. In this review we
      discuss how innate immune system cells affect atherosclerosis pathogenesis. 

PMID- 24326323
TI  - Vitreous base visualisation through trans-scleral illumination with a standard 25
      gauge light probe.
AB  - PURPOSE: To describe a technique of vitreous base visualisation through trans
      scleral illumination using a standard 25-gauge light probe. METHODS: All
      vitrectomies are performed using 25-gauge+ instruments and valved trocars. A non
      contact viewing system is used to visualise the retina. After core vitrectomy and
      the necessary additional procedures, triamcinolone acetonide (Kenacort) is
      injected in the vitreous cavity. Then, the standard 25-gauge light pipe is
      covered with a sleeve obtained from a 20-gauge venflon cannula. The light
      brightness is increased to 100%, and the light probe used to indent the sclera
      and trans-illuminate the vitreous base. The vitreous cutter is activated between
      the crystals of triamcinolone acetonide and the retinal surface. Complete
      vitreous base shaving is carried out for 360 degrees . RESULTS: Iatrogenic
      peripheral retinal tears, as a result of vitreous shaving, occurred in 4.1% of
      cases with this technique. CONCLUSIONS: This method represents a valid and low
      cost option to achieve accurate vitreous base shaving.

PMID- 24326324
TI  - Light out of deep darkness, a biography of Arthur Ferguson MacCallan.

PMID- 24326325
TI  - Sectorial loss of retinal ganglion cells in inherited photoreceptor degeneration
      is due to RGC death.
AB  - AIMS: To investigate the cause of retinal ganglion cell (RGC) loss in dystrophic
      aged Royal College of Surgeons (RCS) rats. METHODS: RCS-p+ (dystrophic) female
      rats of postnatal times (P365, P450 and P540) and age-matched RCS-p1 rdy+ (non
      dystrophic) rats were used. In whole-mounted retinas, RGCs were doubly labelled
      with Fluorogold (FG) retrogradely transported from the superior colliculi and
      Brn3a immunohistochemistry. RGC axons were labelled with anti-neurofilament
      antibodies. Automatic image analysis techniques allowed quantification of the
      total population of RGCs per retina and construction of isodensity maps to
      investigate RGC topology. RESULTS: Dystrophic retinas showed at all times studied
      wedge-shaped sectors devoid of FG(+) and Brn3a(+) RGCs. These sectors were also
      devoid of neurofilament-labelled axons. The total number of FG(+)RGC and
      Brn3a(+)RGC per retina was significantly smaller in dystrophic rats at P540,
      revealing RGC death at this age. The total number of FG(+)RGCs was smaller than
      those of Brn3a(+)RGCs at P540, indicating a disturbance of the retrograde axonal
      transport at this age. CONCLUSIONS: RGC double labelling documents that sectorial
      RGC loss in aged dystrophic RCS rats is mainly due to RGC death, although a
      deficit of the retrograde axonal transport exists also at the more advanced ages.

PMID- 24326326
TI  - What is the evidence for systemic effects of intravitreal anti-VEGF agents, and
      should we be concerned?
AB  - Anti-vascular endothelial growth factor (VEGF) therapy has revolutionised the
      treatment of retinal disease, and appears to be very safe. Nevertheless, there
      are several lines of evidence that imply that small doses of these agents could
      potentially have a systemic effect. The clinical significance of these systemic
      effects remains unclear, but further study is indicated. 

PMID- 24326327
TI  - Pushing the envelope.

PMID- 24326328
TI  - The hard truth about human trafficking.

PMID- 24326329
TI  - Prediction of mean corneal power change after pterygium excision.
AB  - PURPOSE: The aim of this study was to predict the mean corneal power change
      preoperatively for simultaneous pterygium excision and cataract extraction.
      METHODS: This study was performed in 2 stages. First, 66 eyes undergoing
      pterygium excision were recruited, and the subjects were divided into 2 groups
      based on a pterygium length of 2.0 mm (group 1: <2.0 mm, group 2: >=2.0 mm).
      Keratometric values (K) were measured before, 1 month after, and 3 months after
      surgery. Multiple regression analyses were used to predict the postoperative mean
      K using preoperative K and morphological factors that significantly affect
      corneal power change. In the second stage, the regression equation was applied to
      50 eyes (23 with pterygium <2.0 mm and 27 with pterygium >=2.0 mm) in several
      clinics. Prediction accuracy was graded based on the difference between the
      calculated mean K and the postoperative mean K. RESULTS: In group 1, the mean Ks
      did not change significantly after the surgery, and therefore, the predicted mean
      K was not statistically different from the preoperative mean K. In group 2, the
      horizontal and mean Ks steepened significantly, and the regression analysis
      predicted the mean K within the range of 0.5 diopter difference in 22 of 31 eyes,
      showing a better approximation compared with the preoperative mean K (P < 0.001).
      The prediction accuracy was verified similarly in other clinics, and the
      regression analysis was useful for pterygium exceeding a length of 2.0 mm.
      CONCLUSIONS: Pterygium exceeding a length of 2.0 mm induced a significant corneal
      power change after surgery. The mean K predicted from the regression analysis
      could be used as an approximation for a simultaneous pterygium and cataract
      surgery.

PMID- 24326330
TI  - Successful Muller muscle-conjunctiva resection in patients with Boston
      keratoprosthesis type I.
AB  - PURPOSE: To present a case series of patients with Boston keratoprosthesis type I
      (KPro) who have had successful ptosis repair with Muller muscle-conjunctiva
      resection (MMCR). METHODS: Patients with KPros managed with MMCR for ptosis were
      identified. Records were examined to obtain preoperative and postoperative visual
      acuity, KPro viability, and eyelid measurements including margin-to-reflex
      distance 1 (MRD1), levator function, and lagophthalmos. RESULTS: Seven eyes of 6
      patients with KPros and ptosis treated with MMCR were identified. Four eyes
      underwent a lower lid tarsal strip procedure concurrently with the MMCR to
      minimize the risk of exposure to the graft postoperatively. The average time
      between KPro surgery and ptosis surgery was 29.1 months (range, 4-79 months).
      Preoperatively, the average MRD1 was -2.4 mm and the average levator function was
      11.3 mm. Postoperatively, all eyelids were elevated and the average MRD1 was 0.9
      mm. One eye had 0.5 mm of lagophthalmos noted whereas all other eyes had no
      lagophthalmos. The average follow-up time was 25.9 months (range, 13-41 months).
      All 7 eyes maintained a viable KPro without any compromise to the conjunctiva or
      donor corneal tissue. CONCLUSIONS: This retrospective case series describes 7
      eyes with KPros that underwent successful MMCR without compromise to the
      integrity of the KPro. Because these patients are at high risk for potential
      complications, we recommend careful patient selection, a goal of undercorrection,
      and consideration of supplemental procedures to the lower eyelids to minimize
      complications to the KPro.

PMID- 24326331
TI  - Wavefront properties of the anterior and posterior corneal surface after
      photorefractive keratectomy.
AB  - PURPOSE: The aim of this study was to evaluate the balance and changes of corneal
      higher order aberrations (HOAs) after photorefractive keratectomy (PRK). METHODS:
      Myopic and myopic-astigmatic patients (89 eyes of 48 patients) were enrolled in
      this study. A PRK was performed using an Asclepion Meditec MEL 80 G flying-spot
      excimer laser. The mean ablation depth and diameter were 76.78 MUm (+/-19.40 MUm)
      and 6.0 mm (+/-0.06 mm), respectively. Before and 1 year after the surgery,
      uncorrected and best spectacle-corrected visual acuities were determined.
      Wavefront aberrations of the anterior [root mean square (RMS)-HOA anterior],
      posterior (RMS-HOA posterior), and total cornea (RMS-HOA total) were measured
      using a Scheimpflug Camera. Linear piecewise regression analysis was used for
      correlations between the ablation depth and aberration of the anterior corneal
      surface. The follow-up time was 1 year. RESULTS: At baseline, RMS-HOA anterior
      proved to be significantly higher compared with RMS-HOA total (P < 0.001). After
      the PRK was performed, the RMS-HOA anterior (P < 0.001) and RMS-HOA total values
      (P < 0.001) increased significantly; however, RMS-HOA posterior values (P = 0.12)
      remained stable. Above an ablation depth of 76.78 MUm, the RMS-HOA anterior
      increased 2.4-fold. Uncorrected and best spectacle-corrected visual acuities were
      1.0 (20/20) in 95.5% and 98.8% of the patients 1 year postoperatively.
      CONCLUSIONS: Aberrations of the posterior corneal surface seem to compensate for
      wavefront alterations of the anterior cornea, decreasing the amount of wavefront
      error regarding the total cornea in myopic patients. PRK induced increased HOAs
      with respect to the anterior corneal surface; however, the posterior surface
      remained stable. The increase in the HOAs was measured to be significantly larger
      above 76.78 MUm photoablation depth.

PMID- 24326332
TI  - A review of quality of life measures in dry eye questionnaires.
AB  - PURPOSE: Dry eye disease (DED) is an ocular disease that affects 5% to 17% of the
      US population. Because of the negative effects of DED on patients' quality of
      life (QOL), disease-specific questionnaires that assess QOL in patients with dry
      eyes are essential in the monitoring and management of this chronic ocular
      condition. This review provides clinicians and researchers with a summary of the
      current questionnaires available for assessing QOL in patients with dry eyes.
      METHODS: A systematic review of the literature was performed in March 2013.
      RESULTS: There are only 2 validated, reliable dry eye questionnaires with QOL
      measures currently available for clinic use: the Ocular Surface Disease Index
      (OSDI) and the Impact of Dry Eye on Everyday Life questionnaire (IDEEL). Multiple
      other dry eye questionnaires assess some degree of QOL, but they have either not
      been tested for validity and reliability or are limited in QOL measures they
      assess. CONCLUSIONS: The OSDI and IDEEL are validated, reliable disease-specific
      questionnaires that assess QOL measures in patients with DED. Because of its
      extensive development process and multiple QOL measures, the IDEEL offers a more
      thorough assessment of the effect of DED on QOL for clinical trials, whereas the
      OSDI may be the more convenient option for clinical use as a result of its
      shorter completion time. Other questionnaires used to assess QOL in DED (eg, 25
      item National Eye Institute Visual Function Questionnaire and Texas Eye Research
      and Technology Center DEQ) are fairly limited in this assessment. Finally,
      because of the negative effects of DED on QOL, this review emphasizes the
      importance of including QOL measures in future questionnaires for the monitoring
      and management of DED.

PMID- 24326333
TI  - Bevacizumab in the treatment of pterygium: a meta-analysis.
AB  - PURPOSE: The aim of this study was to assess the efficacy and safety of
      bevacizumab in the treatment of pterygium and to mainly explore its effects on
      recurrence rate and complications. METHODS: We searched MEDLINE, EMBASE, Web of
      Science, and Cochrane Central Register from the inception to July 2013 for
      relevant randomized controlled trials that examined bevacizumab therapy for
      pterygium. Data concerning study design, patient characteristics, treatment, and
      outcomes were extracted. The methodological quality of the studies included was
      assessed using the Jadad score. Relative risk (RR) was calculated for recurrence
      rate and complications. RESULTS: A total of 474 patients with 482 eyes in 9
      randomized controlled trials were analyzed. The pooled estimate showed that
      bevacizumab had no statistically significant effect on preventing pterygium
      recurrence [RR 0.90, 95% confidence interval (CI) 0.77-1.07, P = 0.23]. None of
      the subgroup analyses yielded significant results in favor of bevacizumab
      (surgery group: RR 0.77, 95% CI 0.50-1.18, P = 0.23; nonsurgery group: RR 0.98,
      95% CI 0.86-1.11, P = 0.76; primary pterygium group: RR 0.82, 95% CI 0.53-1.26, P
      = 0.36; recurrent pterygium group: RR 0.95, 95% CI 0.82-1.09, P = 0.44). There
      were no statistically significant differences in the complications between the 2
      groups (RR 1.00, 95% CI 0.73-1.37, P = 1.00). However, the bevacizumab group was
      associated with a higher risk of developing subconjunctival hemorrhage (RR 3.34,
      95% CI 1.07-10.43, P = 0.04). CONCLUSIONS: Topical or subconjunctival bevacizumab
      was relatively safe and well tolerated, but it had no statistically significant
      effect on preventing pterygium recurrence. A large-scale trial with a suitable
      dosage and a longer follow-up would be required to rule out the possibility of
      any treatment benefit.

PMID- 24326334
TI  - In vitro pilot analysis of uniformity, circularity, and concentricity of DSAEK
      donor endothelial grafts prepared by a microkeratome.
AB  - PURPOSE: The aim of this study was to analyze Descemet stripping automated
      endothelial keratoplasty donor endothelial grafts, prepared by using a
      microkeratome, in terms of uniformity, circularity, and concentricity. METHODS:
      In this pilot study, 12 human donor corneas were prepared by means of a
      microkeratome and imaged using the Visante anterior segment optical coherence
      tomography along 4 meridians. The microkeratome enters and exits the corneal
      tissue at an angle, creating a donor graft bed with a uniform stromal (US)
      thickness in between the angled edges. We termed the angled portion the
      "nonuniform stromal transitional annulus" (STA), the point of entry and exit of
      the microkeratome the "epithelium-to-epithelium" (E-E) diameter, and the length
      of the US bed the "US" diameter. The E-E and US diameters were measured to create
      a model of each donor graft, from which circularity and concentricity were
      calculated. The STA length and height were measured, and the slope was
      calculated. RESULTS: The mean E-E diameter was 10.69 +/- 0.32 mm (range, 9.46
      11.75 mm) and the mean US diameter was 8.96 +/- 0.40 mm (range, 7.62-10.28 mm).
      The microkeratome generated elliptical rather than circular cuts, with a mean
      eccentricity of 0.34 +/- 0.098 (range, 0.22-0.58). Eccentricity values between 0
      and 1 represent ellipses, with zero characterizing a circle. The US ellipses and
      E-E ellipses were not concentric, with a mean deviation of the centers of the
      shapes of 177.06 +/- 92.06 MUm (range, 21.95-322.22 MUm). The mean STA length was
      0.73 +/- 0.31 mm (range, 0.25-1.89 mm), the mean height was 0.43 +/- 0.08 mm
      (range, 0.28-0.64 mm), and the mean slope was 34.11 +/- 14.00 degrees  (range,
      8.43-53.67 degrees ). CONCLUSIONS: Microkeratome cuts created nonuniform,
      noncircular nonconcentric donor grafts. Asymmetry and nonuniformity of donor
      tissue may help explain suboptimal visual outcomes.

PMID- 24326335
TI  - Observation of replacement of carbon in benzene with nitrogen in a low
      temperature plasma.
AB  - Selective activation of benzene has been mainly limited to the C-H activation.
      Simple replacement of one carbon in benzene with another atom remains unresolved
      due to the high dissociation energy. Herein, we demonstrate a direct breakage of
      the particularly strong C = C bond in benzene through ion-molecule reaction in a
      low-temperature plasma, in which one carbon atom was replaced by one atomic
      nitrogen with the formation of pyridine. The mechanism for the formation of
      pyridine from benzene has been proposed based on the extensive investigation with
      tandem mass spectrometry. The reaction pathway also works to other aromatics such
      as toluene and o-xylene. This finding provides a new avenue for selective
      conversion of aromatics into nitrogen-containing compounds. 

PMID- 24326336
TI  - Like/dislike analysis using EEG: determination of most discriminative channels
      and frequencies.
AB  - In this study, we have analyzed electroencephalography (EEG) signals to
      investigate the following issues, (i) which frequencies and EEG channels could be
      relatively better indicators of preference (like or dislike decisions) of
      consumer products, (ii) timing characteristic of "like" decisions during such
      mental processes. For this purpose, we have obtained multichannel EEG recordings
      from 15 subjects, during total of 16 epochs of 10 s long, while they were
      presented with some shoe photographs. When they liked a specific shoe, they
      pressed on a button and marked the time of this activity and the particular epoch
      was labeled as a LIKE case. No button press meant that the subject did not like
      the particular shoe that was displayed and corresponding epoch designated as a
      DISLIKE case. After preprocessing, power spectral density (PSD) of EEG data was
      estimated at different frequencies (4, 5, ..., 40 Hz) using the Burg method, for
      each epoch corresponding to one shoe presentation. Each subject's data consisted
      of normalized PSD values (NPVs) from all LIKE and DISLIKE cases/epochs coming
      from all 19 EEG channels. In order to determine the most discriminative
      frequencies and channels, we have utilized logistic regression, where
      LIKE/DISLIKE status was used as a categorical (binary) response variable and
      corresponding NPVs were the continuously valued input variables or predictors. We
      observed that when all the NPVs (total of 37) are used as predictors, the
      regression problem was becoming ill-posed due to large number of predictors
      (compared to the number of samples) and high correlation among predictors. To
      circumvent this issue, we have divided the frequency band into low frequency (LF)
      4-19 Hz and high frequency (HF) 20-40 Hz bands and analyzed the influence of the
      NPV in these bands separately. Then, using the p-values that indicate how
      significantly estimated predictor weights are different than zero, we have
      determined the NPVs and channels that are more influential in determining the
      outcome, i.e., like/dislike decision. In the LF band, 4 and 5 Hz were found to be
      the most discriminative frequencies (MDFs). In the HF band, none of the
      frequencies seemed offer significant information. When both male and female data
      was used, in the LF band, a frontal channel on the left (F7-A1) and a temporal
      channel on the right (T6-A2) were found to be the most discriminative channels
      (MDCs). In the HF band, MDCs were central (Cz-A1) and occipital on the left (O1
      A1) channels. The results of like timings suggest that male and female behavior
      for this set of stimulant images were similar.

PMID- 24326337
TI  - Introducing treatment strategy for cerebellar ataxia in mutant med mice:
      combination of acetazolamide and 4-aminopyridine.
AB  - Purkinje neurons are the sole output neuron of the cerebellar cortex, and they
      generate high-frequency action potentials. Electrophysiological dysfunction of
      Purkinje neurons causes cerebellar ataxia. Mutant med mice have the lack of
      expression of the Scn8a gene. This gene encodes the NaV1.6 protein. In med
      Purkinje neurons, regular high-frequency firing is slowed, and med mice are
      ataxic. The aim of this study was to propose the neuroprotective drugs which
      could be useful for ataxia treatment in med mice, and to investigate the
      neuroprotective effects of these drugs by simulation. Simulation results showed
      that Kv4 channel inhibitors and BK channel activators restored the normal
      electrophysiological properties of the med Purkinje neurons. 4-Aminopyridine (4
      AP) and acetazolamide (ACTZ) were proposed as neuroprotective drugs for Kv4
      channel inhibitor and BK channel activator, respectively. 

PMID- 24326339
TI  - New rubrolides from the marine-derived fungus Aspergillus terreus OUCMDZ-1925.
AB  - Two new rubrolides, rubrolides R (1) and S (2), were isolated from the
      fermentation broth of the marine-derived fungus Aspergillus terreus OUCMDZ-1925.
      Their structures were elucidated on the basis of spectroscopic analysis and X-ray
      single crystal diffraction. Compound 1 showed comparable or superior
      antioxidation against 2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS)
      radicals to those of trolox and ascorbic acid with an IC50 value of 1.33 mM.
      Compound 2 showed comparable or superior anti-influenza A (H1N1) virus activity
      to that of ribavirin with an IC50 value of 87.1 MUM. Both compounds 1 and 2
      showed weak cytotoxicity against the K562 cell line with IC50 values of 12.8 and
      10.9 MUM, respectively.

PMID- 24326338
TI  - Mangromicins A and B: structure and antitrypanosomal activity of two new
      cyclopentadecane compounds from Lechevalieria aerocolonigenes K10-0216.
AB  - Two new cyclopentadecane antibiotics, named mangromicins A and B, were separated
      out from the culture broth of Lechevalieria aerocolonigenes K10-0216 by Diaion HP
      20, silica gel and ODS column chromatography, and were finally purified by HPLC.
      The chemical structures of the two novel compounds were elucidated by
      instrumental analyses, including various NMR, MS and X-ray crystallography.
      Mangromicins A and B consist of cyclopentadecane skeletons with a tetrahydrofuran
      unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. Mangromicins A and B showed in
      vitro antitrypanosomal activity with IC50 values of 2.4 and 43.4 MUg ml(-1),
      respectively. The IC50 values of both compounds were lower than those of
      cytotoxicity against MRC-5 human fetal lung fibroblast cells. 

PMID- 24326340
TI  - Inhibition of indoleamine 2,3-dioxygenase by thielavin derivatives from a soil
      fungus, Coniochaeta sp. 10F058.

PMID- 24326341
TI  - Molecular characterization of multidrug-resistant Mycobacterium tuberculosis
      isolated from south-central in China.
AB  - Rifampicin (RIF) and isoniazid (INH) Mycobacterium tuberculosis isolates were
      characterized from south-central China and transmission patterns within the
      Beijing genotype were detected in multidrug-resistant isolates. Six genetic
      regions, including rpoB for RIF, and katG, inhA, ahpC, mabA-inhA promoter and
      oxyR-ahpC intergenic region for INH were analyzed by DNA sequencing in 60
      multidrug-resistant isolates, including 7 extensively drug-resistant isolates.
      The genomic deletion RD105 was characterized by genotyping. The results showed
      that 91.7% of MDR isolates carried mutations in the rpoB gene and 85.0% of the
      MDR isolates had at least one mutation in the INH resistance-associated loci
      detected. In total, these six genetic regions are responsible for 95.0% of MDR
      isolates. Mutations in the XDR isolates were focused on rpoB 531 or rpoB 526, and
      katG 315, correlating to a higher frequency level of resistance to RIF MIC ?8 MUg
      ml-1 and INH MIC ?4 MUg m-1. Three novel katG mutants (G273S, I266T and P232S)
      and three new alleles (E458A, S509R and P535S) in the rpoB gene were identified.
      Among the 85 clinical isolates, 78 are Beijing genotypes and the other 7 are non
      Beijing genotypes. The results present the identification of genetic markers in
      M. tuberculosis isolates, some of which may be unique to this particular
      geographic niche. An understanding of the mutations in these drug-resistant
      strains may aid in choosing the appropriate chemotherapy regimens on the
      pharmacogenetic properties of the mutations for the prevention and control of
      tuberculosis.

PMID- 24326342
TI  - Asymmetric synthesis of N-stereogenic molecules: diastereoselective double aza
      Michael reaction.
AB  - A novel approach towards the asymmetric synthesis of N-stereogenic molecules via
      double aza-Michael addition was developed. The diastereomeric ratio can be
      increased by a thermodynamically controlled isomerization mechanism. Simple
      separation and functionalization of the products afford N-stereogenic compounds
      in high enantiomeric purity. 

PMID- 24326343
TI  - Membrane potential dye imaging of ventromedial hypothalamus neurons from adult
      mice to study glucose sensing.
AB  - Studies of neuronal activity are often performed using neurons from rodents less
      than 2 months of age due to the technical difficulties associated with increasing
      connective tissue and decreased neuronal viability that occur with age. Here, we
      describe a methodology for the dissociation of healthy hypothalamic neurons from
      adult-aged mice. The ability to study neurons from adult-aged mice allows the use
      of disease models that manifest at a later age and might be more developmentally
      accurate for certain studies. Fluorescence imaging of dissociated neurons can be
      used to study the activity of a population of neurons, as opposed to using
      electrophysiology to study a single neuron. This is particularly useful when
      studying a heterogeneous neuronal population in which the desired neuronal type
      is rare such as for hypothalamic glucose sensing neurons. We utilized membrane
      potential dye imaging of adult ventromedial hypothalamic neurons to study their
      responses to changes in extracellular glucose. Glucose sensing neurons are
      believed to play a role in central regulation of energy balance. The ability to
      study glucose sensing in adult rodents is particularly useful since the
      predominance of diseases related to dysfunctional energy balance (e.g. obesity)
      increase with age.

PMID- 24326344
TI  - Single crystal study of antiferromagnetic CePd3Al9.
AB  - Single crystal x-ray diffraction, magnetic susceptibility (M), heat capacity (C),
      and electrical resistivity (rho) measurements are reported for specimens of the
      new tetragonal compound CePd3Al9, which forms in a new structure type. X-ray
      diffraction measurements reveal that the nearest neighbor Ce-Ce distances are
      large (d(Ce-Ce) = 5.272 A), suggesting that this compound may be described as a
      stoichiometric dilute Kondo lattice. Thermodynamic and transport measurements
      reveal antiferromagnetic order near T(N) = 0.9 K. The ordered ground state
      emerges from a lattice of localized Ce ions that are weakly hybridized with the
      conduction electrons, as revealed by the moderate electronic coefficient of the
      specific heat gamma ~ 45 mJ mol(-1) K(-2) (extrapolated from above T(N)) and the
      lack of evidence for Kondo coherence in the magnetic susceptibility and
      electrical resistivity. The application of a magnetic field initially suppresses
      the magnetic order at a rate of -0.04 K kOe(-1), but Zeeman splitting of the
      doublet ground state produces a nonmagnetic singlet before TN reaches zero. The
      data additionally reveal that chemical/structural disorder plays an important
      role, as evidenced by results from single crystal x-ray diffraction, the
      broadness of the peak at TN in the heat capacity, and the small residual
      resistivity ratio RRR = rho(300 K)/rho0 = 1.3.

PMID- 24326345
TI  - A novel (99m)Tc labelling strategy for the development of silica based particles
      for medical applications.
AB  - The reaction of high-valent fac-{(99m)TcO3}(+) complexes with alkenes ((3 + 2)
      cycloaddition) has been used to develop a novel labelling procedure for silica
      based particles. This strategy can help to gain more detailed in vivo data of
      mesoporous silica by non-invasive radioimaging in the future. By applying
      norbornene as a coupling unit the (3 + 2)-cycloaddition reaction proceeds
      stereoselectively and with high reaction rates. 

PMID- 24326346
TI  - Liver functional genomics in beef cows on grazing systems: novel genes and
      pathways revealed.
AB  - The adaptation of the liver to periods of negative energy balance is largely
      unknown in beef cattle on grazing systems. We evaluated liver transcriptome
      throughout gestation and early lactation of purebred and crossbred beef cows
      [Angus, Hereford, and their F1 crossbreeds (CR)], grazing high or low herbage
      allowances (HA) of native grasslands (4 and 2.5 kg dry matter/kg body wt annual
      mean; n = 16) using an Agilent 4 * 44k bovine array. A total of 4,661 transcripts
      were affected by days [272 >= 2.5-fold difference, false discovery rate (FDR) <=
      0.10] and 47 pathways were altered during winter gestation (-165 to -15 days
      relative to calving), when cows experienced decreased body condition score,
      decreased insulin, and increased nonesterified fatty acid concentrations.
      Gluconeogenesis and fatty acid oxidation pathways were upregulated, while cell
      growth, DNA replication, and transcription pathways were downregulated (FDR <=
      0.25). We observed only small changes in the liver transcriptome during early
      lactation (+15 to +60 days). A total of 225 genes were differentially expressed
      (47 >= 2-fold difference, FDR <= 0.10) between HA. The majority of those were
      related to glucose and pyruvate metabolism and were upregulated in high HA,
      reflecting their better metabolic status. Two genes were upregulated in CR cows,
      but 148 transcripts (74 >= 2-fold change difference, FDR <= 0.10) were affected
      by the HA and cow genotype interaction. The transcriptional changes observed
      indicated a complex and previously unrecognized, hepatic adaptive program of
      grazing beef cows in different nutritional environments. Novel target candidate
      genes, metabolic pathways, and regulatory mechanisms were reported.

PMID- 24326348
TI  - Next-generation sequencing of microRNAs uncovers expression signatures in
      polarized macrophages.
AB  - microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at a
      posttranscriptional level and play a crucial role in the development of cells of
      the immune system. Macrophages are essential for generating inflammatory
      reactions upon tissue damage and encountering of invading pathogens, yet
      modulation of their immune responses is critical for maintaining tissue
      homeostasis. Macrophages can present different phenotypes, depending on the
      cytokine environment they encounter in the affected tissues. In this study, we
      have identified expression signatures of miRNAs that are differentially regulated
      during maturation of monocytes and polarization of macrophages by cytokines. We
      present a comprehensive characterization of miRNA expression in human monocytes
      and M1, M2a, and M2c polarized macrophages, using next-generation sequencing.
      Furthermore, we show that miRNA expression signatures are closely related to the
      various immune functions of polarized macrophages and therefore are involved in
      shaping the diverse phenotypes of these cells. The miRNAs identified here serve
      as markers for identification of inflammatory macrophages involved in the
      development of immune responses. Our findings contribute to understanding the
      role of miRNAs in determining the macrophage function in healthy and diseased
      tissues. 

PMID- 24326347
TI  - QTL mapping in outbred populations: successes and challenges.
AB  - Quantitative trait locus (QTL) mapping in animal populations has been a
      successful strategy for identifying genomic regions that play a role in complex
      diseases and traits. When conducted in an F2 intercross or backcross population,
      the resulting QTL is frequently large, often encompassing 30 Mb or more and
      containing hundreds of genes. To narrow the locus and identify candidate genes,
      additional strategies are needed. Congenic strains have proven useful but work
      less well when there are multiple tightly linked loci, frequently resulting in
      loss of phenotype. As an alternative, we discuss the use of highly recombinant
      outbred models for directly fine-mapping QTL to only a few megabases. We discuss
      the use of several currently available models such as the advanced intercross
      (AI), heterogeneous stocks (HS), the diversity outbred (DO), and commercially
      available outbred stocks (CO). Once a QTL has been fine-mapped, founder sequence
      and expression QTL mapping can be used to identify candidate genes. In this
      regard, the large number of alleles found in outbred stocks can be leveraged to
      identify causative genes and variants. We end this review by discussing some
      important statistical considerations when analyzing outbred populations. Fine
      resolution mapping in outbred models, coupled with full genome sequence, has
      already led to the identification of several underlying causative genes for many
      complex traits and diseases. These resources will likely lead to additional
      successes in the coming years.

PMID- 24326349
TI  - Transcriptome sequencing reveals differences between anagen and telogen secondary
      hair follicle-derived dermal papilla cells of the Cashmere goat (Capra hircus).
AB  - Dermal papilla is considered the control center of hair follicle growth and hair
      cycle. The secondary hair follicle (producing cashmere) growth cycle of the
      Cashmere goat (Capra hircus) is circannual, and each growth phase can be easily
      distinguished by its long duration. To identify gene expression patterns and
      differences of the dermal papilla cell (DPC) between the anagen and telogen
      phases, we established two DPC lines: ana-DPCs (DPCs derived from the anagen
      secondary hair follicle) and tel-DPCs (DPCs derived from the telogen secondary
      hair follicle). Compared with the ana-DPCs, the tel-DPCs lost the capacity to
      form cell aggregates and showed lower cell proliferation rate. Transcriptome
      sequencing revealed that 825 genes were differentially expressed by at least
      threefold between the two DPC lines. These genes were significantly enriched in
      cell cycle control, cell division, and chromosome partitioning from the
      Eukaryotic Orthologous Groups of proteins (KOG) database and in cell cycle, cell
      adhesion molecules, cytokine-cytokine receptor interaction, and p53 signaling
      pathway from the Kyoto Encyclopedia of Gene and Genomes (KEGG) database.
      Enrichment analyses revealed that in the middle of the telogen the DPCs of
      secondary hair follicles (SHFs) seemed on the one hand to promote the
      degeneration of SHFs and cessation of cashmere growth, while on the other hand to
      resist self-apoptosis and prepare for the regeneration or revivification of fully
      functional dermal papillae. These findings provide a better understanding of hair
      follicle growth and will be useful for identification of novel molecules
      associated with the control of hair growth cycle. 

PMID- 24326351
TI  - Characterization of a thermostable 2,4-diaminopentanoate dehydrogenase from
      Fervidobacterium nodosum Rt17-B1.
AB  - 2,4-Diaminopentanoate dehydrogenase (2,4-DAPDH), which is involved in the
      oxidative ornithine degradation pathway, catalyzes the NAD(+)- or NADP(+)
      dependent oxidative deamination of (2R,4S)-2,4-diaminopentanoate (2,4-DAP) to
      form 2-amino-4-oxopentanoate. A Fervidobacterium nodosum Rt17-B1 gene, Fnod_1646,
      which codes for a protein with sequence similarity to 2,4-DAPDH discovered in
      metagenomic DNA, was cloned and overexpressed in Escherichia coli, and the gene
      product was purified and characterized. The purified protein catalyzed the
      reduction of NAD(+) and NADP(+) in the presence of 2,4-DAP, indicating that the
      protein is a 2,4-DAPDH. The optimal pH and temperature were 9.5 and 85 degrees C,
      respectively, and the half-denaturation time at 90 degrees C was 38 min.
      Therefore, the 2,4-DAPDH from F. nodosum Rt17-B1 is an NAD(P)(+)-dependent
      thermophilic-alkaline amino acid dehydrogenase. This is the first thermophilic
      2,4-DAPDH reported, and it is expected to be useful for structural and functional
      analyses of 2,4-DAPDH and for the enzymatic production of chiral amine compounds.
      Activity of 2,4-DAPDH from F. nodosum Rt17-B1 was suppressed by 2,4-DAP via
      uncompetitive substrate inhibition. In contrast, the enzyme showed typical
      Michaelis-Menten kinetics toward 2,5-diaminohexanoate. The enzyme was
      uncompetitively inhibited by d-ornithine with an apparent Ki value of 0.1 mM.
      These results suggest a regulatory role for this enzyme in the oxidative
      ornithine degradation pathway.

PMID- 24326353
TI  - Low activation energy for the crystallization of amorphous silicon nanoparticles.
AB  - We have experimentally determined the crystallization rate of plasma-produced
      amorphous silicon powder undergoing in-flight thermal annealing, and have found a
      significant reduction in the activation energy for crystallization compared to
      amorphous silicon thin films. This finding allows us to shed light onto the
      mechanism leading to the formation of high quality nanocrystals in non-thermal
      plasmas. 

PMID- 24326350
TI  - MicroRNAs in normal and psoriatic skin.
AB  - Psoriasis is a chronic and common human skin disorder currently with no cure.
      Psoriatic skin displays inflammatory, raised, and scaly lesions with widely
      aberrant gene expression. Recent studies have revealed critical roles that
      microRNAs play as a class of posttranscriptional gene regulator in skin
      development and skin diseases. A substantial number of novel microRNAs have been
      identified in skin, and much has been learned about the dysregulated expression
      and functional roles of microRNAs in psoriasis, as well as the robustness and
      plasticity of microRNA-mediated gene expression regulation. Here we review recent
      progresses in discovery, profiling, and characterization of microRNAs in human
      psoriatic skin, discuss insights to their biological functions, and share our
      view on remaining challenges to be addressed. 

PMID- 24326352
TI  - Glycosylation analysis of an aggregated antibody produced by Chinese hamster
      ovary cells in bioreactor culture.
AB  - N-Glycosylation of therapeutic antibodies contributes not only to their
      biological function, but also to their stability and tendency to aggregate. Here,
      we investigated the impact of the glycosylation status of an aggregated antibody
      that accumulated during the bioreactor culture of Chinese hamster ovary cells.
      High-performance liquid chromatography analysis showed that there was no apparent
      difference in the glycosylation patterns of monomeric, dimeric, and large
      aggregated forms of the antibody. In contrast, lectin binding assays, which
      enable the total amounts of specific sugar residues to be detected, showed that
      both galactose and fucose residues in dimers and large aggregates were reduced to
      70-80% of the amount in monomers. These results strongly suggest that the lack of
      N-linked oligosaccharides, a result of deglycosylation or aglycosylation,
      occurred in a proportion of the dimeric and large aggregated components. The
      present study demonstrates that glycosylation heterogeneities are a potential
      cause of antibody aggregation in cell culture of Chinese hamster ovary cells, and
      that the lack of N-glycosylation promotes the formation of dimers and finally
      results in large aggregates. 

PMID- 24326354
TI  - Effect of antiretroviral therapy on the incidence of cervical neoplasia among HIV
      infected women: a population-based cohort study in Taiwan.
AB  - OBJECTIVE: Cervical cancer has been recognized as one of the AIDS-defining
      cancers since 1993. Receipt of HAART has been shown to reduce the risk of
      opportunistic infection and AIDS-defining malignancies. However, findings
      concerning the effect of HAART on cervical neoplasia have been inconsistent.
      DESIGN: A population-based cohort design was used, in which 1360 HIV-infected
      women were compared to the general population (HIV-negative women). The
      comparison population included 358 141 HIV-negative women randomly selected from
      among all insured persons in Taiwan in 2000. Data from HIV-infected and
      uninfected women were analyzed through 2008. METHODS: The age and calendar year
      standardized incidence ratio was calculated to estimate the relative risk of
      cervical neoplasia, and Cox proportional hazards models were used to assess the
      effect of HAART on the incidence of cervical neoplasia. RESULTS: The incidence of
      cervical neoplasia was four times higher in the HIV-infected women than in the
      general population [standardized incidence ratio 4.0, 95% confidence interval
      (CI) 2.16-6.95]. The most increased risk was noted in HIV-infected women aged 40
      59 years. Receipt of HAART was associated with a significantly reduced risk of
      cervical neoplasia (0.20, 0.05-0.77). The most evident protective effect was
      noted in adherent to HAART at least 85%, and those treated with HAART for more
      than 3 years (0.01, 0.00-0.47). CONCLUSIONS: HIV-infected women have a
      substantially increased risk of cervical neoplasia. Adherent to HAART and
      prolonged HAART for more than 3 years may contribute to a reduction risk of
      cervical neoplasia.

PMID- 24326355
TI  - Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine
      resistant HIV-1.
AB  - OBJECTIVE: The M184V mutation in the HIV-1 reverse transcriptase gene is frequent
      (>50%) in patients, both in resource-rich and resource-limited countries,
      conferring high-level resistance (>100-fold) to the cytosine analog reverse
      transcriptase inhibitors lamivudine and emtricitabine. The reverse transcriptase
      enzyme of M184V HIV-1 mutants has reduced processivity, resulting in reduced
      viral replication, particularly at low deoxynucleotide (dNTP) levels. We
      hypothesized that lowering intracellular dNTPs with resveratrol, a dietary
      supplement, could interfere with replication of M184V HIV-1 mutants. DESIGN AND
      METHODS: Evaluation of the activity of resveratrol on infection of primary
      peripheral blood lymphocytes by wild-type and M184V mutant HIV-1. We assayed both
      molecular clones and primary isolates of HIV-1, containing M184V alone and in
      combination with other reverse transcriptase mutations. Viral infection was
      quantified by p24 ELISA and by quantitative real-time PCR analysis. Cell
      viability was measured by colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assays. RESULTS: In virus-infectivity assays,
      resveratrol did not inhibit replication of wild-type NL4-3 (resveratrol EC50 > 10
      MUmol/l), but it inhibited NL4-3 184V mutant (resveratrol EC50 = 5.8 MUmol/l).
      These results were confirmed by real-time PCR analysis of early and late products
      of reverse transcription. Resveratrol inhibited molecular clones and primary
      isolates carrying M184V, alone or in combination with other reverse transcriptase
      mutations (resveratrol EC50 values ranging from 2.5 to 7.7 MUmol/l). CONCLUSIONS:
      Resveratrol inhibits HIV-1 strains carrying the M184V mutation in reverse
      transcriptase. We propose resveratrol as a potential adjuvant in HIV-1 therapy,
      particularly in resource-limited settings, to help control emtricitabine
      resistant M184V HIV-1 mutants.

PMID- 24326357
TI  - [Oncological imaging for therapy response assessment].
AB  - This review illustrates different radiological methods for therapy response
      assessment in the field of oncological imaging. Unidimensional measurement of
      tumor size according to the response evaluation criteria in solid tumors (RECIST)
      is of utmost importance. The established RECIST definitions of changes in size
      are decisive for subdivision into the categories complete response (CR), partial
      response (PR), stable disease (SD) and progressive disease (PD), which are
      generally accepted as the concise characterization for therapy response. Problems
      with size-dependent response assessment occur particularly in targeted therapy
      and by phenomena, such as pseudoprogression. Several variants of functional
      imaging and their role in cancer imaging regarding practical requests are
      introduced. 

PMID- 24326356
TI  - HIV RNA levels in plasma and cervical-vaginal lavage fluid in elite controllers
      and HAART recipients.
AB  - OBJECTIVES: The introduction of HAART leads to control of HIV replication to less
      than 50 copies/ml, similar to levels in 'elite controllers'. Low-level viral
      replication may be one of the contributing factors to persistent immune
      activation/inflammation in HAART-treated individuals. There are still gaps in our
      knowledge of whether low-level replication persists in systemic versus mucosal
      sites. DESIGN AND METHODS: Participants for this study were recruited from the
      Women's Interagency HIV Study. We evaluated 33 'elite controllers' who naturally
      controlled HIV replication and 33 matched HAART-suppressed recipients. This study
      employed a sensitive target-capture transcription-mediated-amplification assay to
      compare low-level virus concentrations in plasma and cervical-vaginal lavage
      (CVL) samples from HIV-positive HAART recipients and 'elite controllers'.
      RESULTS: The median (interquartile range) plasma viral load signal/cut-off (S/Co)
      for 'elite controllers' was 10.5 (3.9-21.1), which was significantly (P < 0.001)
      higher than the S/Co for HAART recipients [2.0 (1-4.9)]. The majority of CVL
      samples from both groups had undetectable HIV RNA and the proportion of CVL
      samples with a cut-off more than 1.0 was not different between 'elite
      controllers' and HAART-suppressed recipients. CONCLUSION: This study demonstrated
      persistent low-level HIV replication in 'elite controllers', suggesting potential
      value of HAART treatment for these individuals. Absent or very low levels of HIV
      RNA in CVL indicate very low risk of secondary sexual transmission for both
      groups.

PMID- 24326358
TI  - A simple and novel system for colorimetric detection of cobalt ions.
AB  - A simple and novel method for the colorimetric detection of Co(2+) was developed
      based on controlling the oxidation level of methylene blue (MB). After a complex
      was formed between MB, 2-aminothiophenol (ATP) and copper nitrate (MB-ATP
      Cu(2+)), the sensing of Co(2+) showed high selectivity. The mechanism of sensing
      has also been discussed. 

PMID- 24326359
TI  - Tension band wiring in olecranon fractures: the myth of technical simplicity and
      osteosynthetical perfection.
AB  - PURPOSE: The tension band wiring (TBW) technique is a common treatment for the
      fixation of olecranon fractures with up to three fragments. The literature and
      surgeons describe TBW as an uncomplicated, always available and convenient
      operation producing excellent results. The purpose of this study was to determine
      whether TBW is more ambitious than believed or the procedure provides an
      increased level of tolerance concerning the surgical technique. METHODS: This
      study reviewed 239 TBW cases in patients with olecranon fractures or osteotomies.
      We reviewed a total of 2,252 X-rays for ten operative imperfections: (1)
      nonparallel K-wires, (2) long K-wires, (3) K-wires extending radially outwards,
      (4) insufficient fixation of the proximal ends of the K-wires, (5) intramedullary
      K-wires, (6) perforation of the joint surface, (7) single wire knot, (8) jutting
      wire knot(s), (9) loose figure-of-eight configuration, and (10) incorrect
      repositioning. RESULTS: On average, there were 4.24 imperfections per
      intervention in the cases reviewed. A total of 1,014 of 2,390 possible
      imperfections were detected. The most frequent imperfections were insufficient
      fixation of the proximal ends of the K-wires (91% of all cases), the use of a
      single wire knot (78%) and nonparallel K-wires (72%). Mayo IIa (n = 188) was the
      most common fracture type. CONCLUSIONS: Our results and the number of
      complications described by the literature together support the conclusion that
      TBW is not as easy as surgeons and the literature suggest. Although bone healing
      and the functional results of TBW are excellent in most cases, the challenges
      associated with this operation are underestimated. LEVEL OF EVIDENCE: IV,
      treatment study.

PMID- 24326360
TI  - Comment on Giannini et al.: A minimally invasive technique for surgical treatment
      of hallux valgus: simple, effective, rapid, inexpensive (SERI).

PMID- 24326361
TI  - Mono- versus polyaxial locking plates in distal femur fractures: a prospective
      randomized multicentre clinical trial.
AB  - PURPOSE: Treatment of complex fractures of the distal femur utilizing monoaxial
      locking plates (e.g. Less Invasive Stabilisation System, LISS(r), Synthes) is
      considered to be superior to conventional plating systems. Due to the limitation
      that the thread forces the screw into pre-determined positions, modifications
      have been made to allow screw positioning within a range of 30 degrees  (Non
      Contact Bridging, NCB(r)-DF, Zimmer). For the first time, this multicenter
      prospective randomized clinical trial (RCT) investigates the outcome of LISS(r)
      vs. NCB(r)-DF treatment following complex fractures of the distal femur. METHODS:
      Since June 2008, 27 patients with a fracture of the distal femur (AO ASIF 33-A-C
      and periprosthetic fractures) were enrolled in this study by four university
      trauma centres in southern Germany. Clinical (e.g. range of motion, Oxford knee
      score, Tegner score) and radiological (e.g. axis deviation, secondary loss of
      realignment) follow-ups were conducted one and six weeks, as well as three, six,
      and 12 months after the operation. RESULTS: This study comprises data of 27
      patients (8 male, 19 female; 15 NCB(r)-DF, 12 LISS(r)). Polyaxial osteosynthesis
      using the NCB(r) system tended to result in better functional knee scores and a
      higher range of motion. Interestingly, fracture union tended to be more rapid
      using the polyaxial plating system. CONCLUSIONS: We present the analysis of a
      multicenter prospective RCT to compare the monoaxial LISS(r) vs. the polyaxial
      NCB(r)-DF treatment following complex fractures of the distal femur. NCB(r)-DF
      treatment tended to result in better functional and radiological outcomes than
      LISS(r) treatment. LEVEL OF EVIDENCE: Level I.

PMID- 24326362
TI  - Expression of glucagon-like Peptide 1 receptor and its effects on biologic
      behavior in pancreatic neuroendocrine tumors.
AB  - OBJECTIVES: Glucagon-like peptide 1 (GLP-1) interacts with its specific high
      affinity receptor, glucagon-like peptide 1 receptor (GLP-1R), and induces
      cellular growth and inhibition of apoptosis in pancreatic beta cells. The aim of
      this study was to investigate the significance of GLP-1R expression in pancreatic
      neuroendocrine tumors (PNETs). METHODS: Glucagon-like peptide 1 receptor
      expression was semiquantitatively evaluated by immunohistochemical staining in 50
      resected PNETs, and the correlation between the GLP-1R expression and
      clinicopathologic features was investigated. RESULTS: There were 23 PNETs with
      positive expression and 27 PNETs with negative expression of GLP-1R. Positive
      expression of GLP-1R was more frequently observed in insulinoma than in
      gastrinoma and nonfunctioning tumor (P < 0.05). Although expression status of GLP
      1R did not affect the prognosis of the patients with PNETs (P = 0.82), most of
      the metastatic sites such as lymph node and liver showed positive staining for
      GLP-1R (8 of 11 PNETs, 73%). CONCLUSIONS: Glucagon-like peptide 1 receptor would
      be a diagnostic marker of insulinoma and might become a molecular target for
      treatment of metastatic PNETs and hormonal regulation of insulin.

PMID- 24326363
TI  - RC-3095, a gastrin-releasing peptide receptor antagonist, synergizes with
      gemcitabine to inhibit the growth of human pancreatic cancer CFPAC-1 in vitro and
      in vivo.
AB  - OBJECTIVES: Pancreatic cancer remains a lethal disease. In this study, we
      investigated the efficacy of a combination of gastrin-releasing peptide receptor
      antagonist RC-3095 and gemcitabine on pancreatic cancer CFPAC-1. METHODS: The
      antiproliferation effects of RC-3095, gemcitabine, or the combination on
      pancreatic cancer were monitored in vitro. Nude mice bearing xenografts of CFPAC
      1 cell received injections of the vehicle (control), RC-3095 (20 MUg,
      subcutaneously, daily), gemcitabine (15 mg/kg, intraperitoneally, every 3 days),
      or the combination of RC-3095 and gemcitabine for 4 weeks. The histological
      changes and protein expression were tested using immunohistochemistry and Western
      blotting. RESULTS: Treatment with the combination in culture exhibited a powerful
      inhibition effect on CFPAC-1 cell proliferation. In xenograft mice model, RC-3095
      or gemcitabine significantly reduced the volume and weight of tumors after 4
      weeks of treatment, as compared with controls. The combination more potently
      inhibited the tumor growth than either agent used individually.
      Immunohistochemistry and Western blotting showed gastrin-releasing peptide
      receptor/bombesin receptor subtype-3 positive cells and protein expression in
      tumors decreased by treatment with RC-3095 or gemcitabine alone or greater in
      combination. CONCLUSIONS: Our data suggested that the combination could be
      considered for the possible new approaches for treatment of pancreatic cancers.

PMID- 24326365
TI  - Acute alcohol-induced pancreatic injury is similar with intravenous and
      intragastric routes of alcohol administration.
AB  - OBJECTIVES: Five percent of alcoholics develop an acute pancreatitis (AP). The
      mechanism leading to pancreatic injury is not yet understood. Microcirculatory
      disorders seem to play a pivotal role. The objective of this study was to compare
      alcoholic pancreatic injury in response to intravenous and intragastric routes of
      alcohol administration. METHODS: Alcohol was applied in rats intravenously (IV)
      or gastric via a surgical implanted feeding tube (IG). Serum alcohol
      concentration was maintained between 1.50/00 and 2.50/00. Four subgroups (n =
      6/group) were examined in the IV/IG arm and compared with healthy controls.
      Pancreatic microcirculation, enzyme levels, and morphological damage were
      assessed after 3, 6, 12, and 24 hours. RESULTS: Microcirculatory analysis showed
      significantly disturbed pancreatic perfusion and increased adherent leukocytes in
      IV and IG animals. In IV and IG groups, serum amylase was increased without
      morphological signs of AP compared with healthy controls. CONCLUSIONS: Alcohol
      application does not induce AP in rodents, but impairs pancreatic
      microcirculation irrespectively of the application route. Intravenous application
      is commonly used and shows no disadvantages compared with the physiological
      intragastric application form. Therefore, the intravenous route offers a valid
      model, which mimics the physiological process for further studies of the
      influence of acute alcohol intoxication on the pancreas.

PMID- 24326364
TI  - Potential prognostic biomarkers of pancreatic cancer.
AB  - OBJECTIVES: We evaluated whether pancreatic main duct fluid can provide protein
      biomarkers with prognostic value. METHODS: Mass spectrometry proteomics was
      applied to as little as 20uL of fluid collected at the time of tumor surgical
      resection. Biomarker proteins identified for 27 patients were correlated with
      clinical outcomes. RESULTS: Thirteen patients had pancreatic ductal
      adenocarcinomas, 4 had intraductal papillary mucinous neoplasm with in situ
      adenocarcinoma, 5 had ampullary adenocarcinomas, 2 had intraductal papillary
      mucinous neoplasms, and 3 had benign diseases. In pathologic stage II or higher
      pancreatic ductal adenocarcinoma, moderate or high expression of S100A8 or S100A9
      proteins was associated with a median disease recurrence-free survival of 5.8
      months compared with 17.3 months in patients with low expression (P = 0.002).
      Median overall survival was 12.6 versus 27 months for patients with moderate to
      high versus low S100A8 and A9 expression (P = 0.02). CONCLUSIONS: This analysis
      suggests distinct proteomic signatures for pancreatic cancer. Patients in our
      study with elevated levels of S100A8 or A9 in the ductal fluid, a near absence of
      pancreatic enzymes, and high levels of mucins were found to have significantly
      worse prognosis. Although further validation is needed to corroborate these
      findings, analysis of pancreatic ductal fluid is a promising tool for identifying
      biomarkers of interest.

PMID- 24326368
TI  - Endoscopic ultrasound and pancreas divisum.

PMID- 24326366
TI  - Opuntia humifusa ameliorated cerulein-induced acute pancreatitis.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of Opuntia humifusa
      (OH) on cerulein-induced acute pancreatitis (AP). METHODS: Acute pancreatitis was
      induced via intraperitoneal injection of cholecystokinin analog cerulein (50
      MUg/kg). In the OH pretreatment group, OH was administered intraperitoneally
      (100, 250, or 500 mg/kg) 1 hour before first cerulein injection. In the
      posttreatment group, OH was administered intraperitoneally (500 mg/kg) 1 hour
      after the first cerulein injection. Furthermore, we isolated the pancreatic
      acinar cells using collagenase method, then investigated the acinar cell
      viability, cytokine productions, and the regulating mechanisms. RESULTS: The both
      pretreatment and posttreatment of OH treatment attenuated the severity of AP, as
      shown by the histology of the pancreas and lung, and inhibited neutrophil
      infiltration; serum amylase and lipase activities; proinflammatory cytokine
      expression such as interleukin 1, interleukin 6, and tumor necrosis factor alpha;
      and cell death including apoptosis and necrosis. Furthermore, OH inhibited the
      activation of c-Jun N-terminal kinases. CONCLUSIONS: These results suggest that
      OH reduces the severity of AP by inhibiting acinar cell death through c-Jun N
      terminal kinases.

PMID- 24326367
TI  - B7-H4 expression in normal and diseased human islet beta cells.
AB  - OBJECTIVES: B7-H4 is a negative coregulatory molecule known to be involved in
      immune response. We study here B7-H4 expression and its possible role in diabetes
      and cancer development. METHODS: Formalin-fixed, paraffin-processed pancreas
      samples from patients with type 1 diabetes (T1D), insulinoma, pancreatic ductal
      adenocarcinoma (PDAC), and normal organ donors were studied by bright-field and
      multifluorescence immunohistochemistry to examine B7-H4 expression and its
      colocalization with islet endocrine hormones. Quantitative RT-PCR and Western
      blot assay were used to examine B7-H4 mRNA and protein expression in the islet
      and exocrine tissues from normal donors and pancreatic cancer cell lines.
      RESULTS: B7-H4 protein expression in islet beta cells is decreased in T1D and
      PDAC, but increased in insulinoma patients when compared to normal controls; the
      changes in B7-H4 expression are concomitant with insulin expression on the islet
      beta cells. The insulin/B7-H4 colocalization on the beta cells, expressed in
      colocalization coefficient Pearson r, is also changed in these islets.
      CONCLUSIONS: Our observation of altered B7-H4 expression, concomitant with
      insulin expression, in the pancreatic islets of T1D, PDAC, and insulinoma
      patients when compared to normal controls suggests that B7-H4 pathway might play
      an important role in maintenance of beta-cell function, but its exact role
      remains to be explored.

PMID- 24326369
TI  - Issues in the design and analysis of a small external validation study.

PMID- 24326370
TI  - Reply: To PMID 23429493.

PMID- 24326371
TI  - Exocrine pancreas hyperplasia without dysplasia in glucagon receptor knockout
      mice.

PMID- 24326372
TI  - Multiple endocrine neoplasia type 1 associated with a new mutation in the menin
      gene and a midgut neuroendocrine tumor.

PMID- 24326373
TI  - A novel mutation in the cystic fibrosis transmembrane conductance regulator gene
      in an Indian patient with idiopathic chronic pancreatitis: a case report.

PMID- 24326374
TI  - Endoscopic ultrasound should be performed before endoscopic retrograde
      cholangiopancreatography in all patients with mild acute gallstone pancreatitis.

PMID- 24326375
TI  - A new mouse model of chronic pancreatitis in C57BL/6J strain that mimics the
      human pathology.

PMID- 24326376
TI  - Translational research in pancreatic cancer: KRAS and beyond.

PMID- 24326378
TI  - Reaction of L2Zn2 with Ph2E2--synthesis of LZnEPh and reactions with oxygen and H
      acidic substrates.
AB  - L2Zn2 (L = HC[C(Me)N(2,4,6-Me3C6H2)]2) and Ph2E2 (E = Se, Te) react to form
      LZnSePh (1) and LZnTePh (2).1 and 2 further react with H2O and EtOH to form LZnOH
      (3) and LZnOEt (4), respectively, whereas the reaction of 2 with oxygen yielded
      [LZnOTe(O)Ph]2 (5). 1, 4 and 5 were characterized by single crystal X-ray
      diffraction.

PMID- 24326377
TI  - Crystal structure and photoluminescence of two europium compounds with
      phenoxyacetic acid and 2,4,6-tri(2-pyridyl)-s-triazine.
AB  - Two novel crystal compounds of Eu(3+) and Gd(3+)/Eu(3+) with phenoxyacetic acid
      (HPOA) and 2,4,6-tri(2-pyridyl)-s-triazine (TPTZ) have been synthesized. The two
      compounds are characterized by elemental analysis, rare earth coordination
      titrations, molar conductivity measurements, UV-vis absorption spectroscopy and
      IR spectroscopy. The crystal structures of compounds 1 Eu2(TPTZ)2(POA)6.2CH3OH
      and 2 EuGd(TPTZ)2(POA)6.2CH3OH were determined by single-crystal X-ray
      diffraction. The two monocrystals belong to the triclinic system and space group
      P1[combining macron] with the following unit cell parameters: a = 12.2448(10),
      12.2476(6) A; b = 13.2214(11), 13.2260(7) A; c = 13.5248(12), 13.5210(7) A; alpha
      = 74.8544(15), 74.8810(10) degrees ; beta = 83.0605(16), 83.0465(8) degrees ;
      gamma = 87.1996(14), 87.2126(8) degrees ; V = 2097.7(7), 2098.5(19) A(3) and Z =
      1, respectively. They are both dinuclear: one is homonuclear and the other is
      heteronuclear. Each metal ion is coordinately bonded to three nitrogen atoms of
      one TPTZ and seven oxygen atoms of three phenoxyacetate ions. Furthermore, there
      exist two coordinate forms between C6H5OCH2COO(-) and metal ions. One is
      chelating bidentate and the other is chelating and bridge coordinating. The
      triplet energy level of phenoxyacetic acid was measured, which is approximately
      22,500 cm(-1), indicating that the lowest excitation state energy level of
      Eu(III) and the triplet state energy level of phenoxyacetic acid match well with
      each other. The luminescent emission intensity of both compounds was very strong.
      Besides, the results indicate that the luminescent emission intensity,
      luminescence lifetimes and the emission quantum efficiencies of Gd(3+)/Eu(3+)
      compound 2 are remarkably superior to those of compound 1, respectively. This
      phenomenon may mainly result from the decrease of the concentration quenching
      effect of Eu(3+) ions, and the intramolecular energy transfer from the ligands
      coordinated with Gd(3+) ions to Eu(3+) ions.

PMID- 24326379
TI  - Restoration of albumin production by nucleoside analogue therapy in patients with
      chronic hepatitis B.
AB  - The clinical course of patients with chronic hepatitis B (CH-B) was greatly
      changed by the introduction of nucleoside analogues. We often encounter patients
      where the serum level of albumin recovers quickly following the treatment. In
      this study, we focused carefully on the changes in serum albumin level noted
      during nucleoside analogue therapy, in an effort to clarify the mechanism behind
      the restoration of albumin production. We observed changes in serum albumin
      levels during nucleoside analogue therapy in 12 patients with CH-B and studied
      the mechanism behind the restoration of albumin production following the therapy.
      The serum level of albumin was significantly increased very soon after the
      treatment was started. Prior to treatment with nucleoside analogues, the albumin
      signal for mRNA was only slightly seen in the peri-portal area, whereas 12 months
      after the treatment, the liver tissue presented an obvious signal of albumin
      mRNA. Serum levels of hepatocyte growth factor (HGF) were significantly decreased
      12 months after the treatment. In this study, we demonstrated that nucleoside
      analogues decrease HGF through the suppression of hepatocyte damage, leading to
      the restoration of albumin production in patients with CH-B.

PMID- 24326380
TI  - Novel PHKG2 mutation causing GSD IX with prominent liver disease: report of three
      cases and review of literature.
AB  - Glycogen storage disease type IX (GSD IX) is a common form of glycogenosis due to
      mutations in PHKA1, PHKA2, or PHKB and PHKG2 genes resulting in the deficiency of
      phosphorylase kinase. The first two genes are X-linked while the latter two
      follow an autosomal recessive inheritance. The majority of cases of GSD IX are
      attributed to defects in PHKA2 which usually cause a mild disease. We report
      three patients with PHKG2-related GSD IX presenting with significant hepatic
      involvement, fibrosis, and cirrhosis. Interestingly, the homozygosity mapping
      resolved a dilemma about an erroneously normal phosphorylase kinase activity in
      patient 1. The novel mutation found in all the three patients (p.G220E) affects
      the catalytic subunit of the phosphorylase kinase. Increasing evidence shows that
      patients with PHKG2 mutations have a severe hepatic phenotype within the
      heterogeneous GSD IX disorder. Therefore, defect in PHKG2 should be considered in
      patients with suspected glycogenosis associated with significant liver fibrosis
      and cirrhosis. 

PMID- 24326381
TI  - Incidence of whooping cough in Spain (1997-2010): an underreported disease.
AB  - Whooping cough is currently the worst controlled vaccine-preventable disease in
      the majority of countries. In order to reduce its morbidity and mortality, it is
      essential to adapt vaccination programmes to data provided by epidemiological
      surveillance. A population-based retrospective epidemiological study to estimate
      the minimum annual undernotification rate of pertussis in Spain from 1997 to 2010
      was performed. The incidence of pertussis cases reported to the National
      Notifiable Disease Surveillance System was compared with the incidence of
      hospital discharges for pertussis from the National Surveillance System for
      hospital data, Conjunto Minimo Basico de Datos. The overall reported incidence
      and that of hospitalisation for whooping cough were 1.3 cases * 100,000
      inhabitants in both cases. Minimum underreporting oscillated between 3.8 and 22.8
      %, according to the year of the study. The greatest underreporting (50 %) was
      observed in children under the age of 1 year. CONCLUSION: Spanish epidemiological
      surveillance system of pertussis should be improved with complementary active
      systems to ascertain the real incidence. Paediatricians and general practitioners
      should be sensibilized to the importance of notification because this would be
      essential for adapting the prevention and control measures of this disease.

PMID- 24326382
TI  - Transport of infants with congenital heart disease: benefits of antenatal
      diagnosis.
AB  - Infants with significant congenital heart disease (CHD) typically require
      transport from their birth centre to a regional paediatric cardiac centre.
      Antenatal diagnosis of CHD allows early pre-emptive stabilisation, and is
      associated with improved early clinical status. However, the effect of antenatal
      diagnosis on the transport characteristics of infants with CHD has not been
      previously investigated. The aim of this study was to compare the transport
      characteristics of infants with antenatal and postnatal diagnosis of CHD. This
      study is a retrospective cohort study of all infants of <=10 days and >=34 weeks
      of gestation with CHD admitted to the Royal Children's Hospital, Melbourne (RCH)
      over 5 years. Demographic, diagnosis, and transport data were recorded. Cases of
      complex CHD were included in this study. Of 320 infants with complex CHD, 198 (62
      %) had antenatal diagnosis (ANdx) and 122 (38 %) had postnatal diagnosis (PNdx).
      There was no significant difference in sex, birth weight, or gestation between
      ANdx and PNdx groups. Average age of referral was 15 vs. 53.4 h in ANdx vs. PNdx
      groups. Aggregate transfer distance in the ANdx group was 2216 km and in the PNdx
      group was 10,274 km (P < 0.0001). Of the infants, 39 % in the PNdx group required
      highest-acuity "time critical" transports compared to 6 % of ANdx infants (P =
      0.0001). Conversely, only 11 % of the infants in the PNdx group had lowest acuity
      "non-urgent" transfers, compared to 24 % of ANdx infants (P = 0.003). PNdx was
      associated with significantly higher rates of invasive ventilation (36 vs 20 %; P
      = 0.01) and higher rates of inotrope use (19 vs. 9 %; P = 0.007) during
      transport. CONCLUSIONS: Improved antenatal detection would allow for safer, less
      resource intense transfers of infants with CHD.

PMID- 24326384
TI  - Interpretation of experimental results on Kondo systems with crystal field.
AB  - We present a simple approach to calculate the thermodynamic properties of single
      Kondo impurities including orbital degeneracy and crystal field effects (CFE) by
      extending a previous proposal by Schotte and Schotte (1975 Phys. Lett. 55A 38).
      Comparison with exact solutions for the specific heat of a quartet ground state
      split into two doublets shows deviations below 10% in the absence of CFE and a
      quantitative agreement for moderate or large CFE. As an application, we fit the
      measured specific heat of the compounds CeCu2Ge2, CePd3Si0.3, CePdAl, CePt,
      Yb2Pd2Sn and YbCo2Zn20. The agreement between theory and experiment is very good
      or excellent depending on the compound, except at very low temperatures due to
      the presence of magnetic correlations (not accounted for in the model). 

PMID- 24326383
TI  - Excess of weight, but not underweight, is associated with poor physical fitness
      in children and adolescents from Castilla-La Mancha, Spain.
AB  - We estimated the prevalence of underweight, overweight and obesity of children
      and adolescents from Castilla-La Mancha region (Spain), applying the new
      International Obesity Task Force (IOTF) 2012 criteria, and analysed differences
      in physical fitness components in relation to weight status. The sample was 2,330
      schoolchildren aged 6-17 years. We measured height and weight, calculated body
      mass index (BMI) and assessed physical fitness using four tests included in the
      EUROFIT battery. Differences in physical fitness components across BMI
      categories, by sex, were calculated using ANOVA models. In children aged 6-11
      years, 4.9 % were underweight, 26.7 % overweight and 11.0 % obese; in adolescents
      aged 12-17 years, 6.4 % were underweight, 16.7 % overweight and 5.8 % obese.
      Overall, overweight and obesity were associated with worse physical fitness but
      students in the underweight category did not score worse than their normal weight
      counterparts on fitness tests. CONCLUSION: Childhood obesity in Spain remains a
      public health problem. Our results show low physical fitness levels in
      overweight/obese children and adolescents and low levels of handgrip strength in
      underweight adolescents compared with normal weight subjects. Exercise programmes
      must be tailored to the specific needs of the subjects according to the different
      weight status.

PMID- 24326385
TI  - Cerebral oxygen metabolism in neonates with congenital heart disease quantified
      by MRI and optics.
AB  - Neonatal congenital heart disease (CHD) is associated with altered cerebral
      hemodynamics and increased risk of brain injury. Two novel noninvasive
      techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation
      spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation
      spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and
      oxygen metabolism (CMRO(2)) of 32 anesthetized CHD neonates at rest and during
      hypercapnia. Cerebral venous oxygen saturation (S(v)O(2)) and CBF were measured
      simultaneously with MRI in the superior sagittal sinus, yielding global oxygen
      extraction fraction (OEF) and global CMRO(2) in physiologic units. In addition,
      microvascular tissue oxygenation (StO(2)) and indices of microvascular CBF (BFI)
      and CMRO(2) (CMRO(2)(i)) in the frontal cortex were determined by DOS/DCS. Median
      resting-state MRI-measured OEF, CBF, and CMRO(2) were 0.38, 9.7 mL/minute per 100
      g and 0.52 mL O(2)/minute per 100 g, respectively. These CBF and CMRO(2) values
      are lower than literature reports for healthy term neonates (which are sparse and
      quantified using different methods) and resemble values reported for premature
      infants. Comparison of MRI measurements of global S(v)O(2), CBF, and CMRO(2) with
      corresponding local DOS/DCS measurements demonstrated strong linear correlations
      (R(2)=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The
      results suggest that MRI and optics offer new tools to evaluate cerebral
      hemodynamics and metabolism in CHD neonates.

PMID- 24326386
TI  - Stress as necessary component of realistic recovery in animal models of
      experimental stroke.
AB  - Over the last decade there has been a considerable effort directed toward
      reformulating the standard approach taken to preclinically model stroke and
      stroke recovery. The principal objective of this undertaking has been to improve
      the success with which preclinical findings can be translated. Although several
      advancements have already been introduced, one potentially critical feature that
      appears to have been overlooked is psychological stress. Stroke is well
      recognized to produce high levels of stress in patients, and ongoing exposure to
      stress is recognized to deleteriously interfere with recovery. The presence of
      high levels of stress (distress) in stroke patients is also relevant because
      nearly all clinically deployed neurorestorative interventions occur against this
      background. Somewhat perplexingly, however, we could find no preclinical stroke
      studies concerned with investigating the efficacy of putative neurorestorative
      compounds that did so in the presence of stress. The following article will make
      the case that failure to recognize or compensate for the effects of ongoing
      stress in standard preclinical experimental models of recovery is likely to
      result in overestimation of the effectiveness of pharmacological or behavioral
      neurorestorative interventions. 

PMID- 24326387
TI  - Inhibiting mitochondrial beta-oxidation selectively reduces levels of
      nonenzymatic oxidative polyunsaturated fatty acid metabolites in the brain.
AB  - Schonfeld and Reiser recently hypothesized that fatty acid beta-oxidation is a
      source of oxidative stress in the brain. To test this hypothesis, we inhibited
      brain mitochondrial beta-oxidation with methyl palmoxirate (MEP) and measured
      oxidative polyunsaturated fatty acid (PUFA) metabolites in the rat brain. Upon
      MEP treatment, levels of several nonenzymatic auto-oxidative PUFA metabolites
      were reduced with few effects on enzymatically derived metabolites. Our finding
      confirms the hypothesis that reduced fatty acid beta-oxidation decreases
      oxidative stress in the brain and beta-oxidation inhibitors may be a novel
      therapeutic approach for brain disorders associated with oxidative stress. 

PMID- 24326388
TI  - Immune cell infiltration in malignant middle cerebral artery infarction:
      comparison with transient cerebral ischemia.
AB  - We tested whether significant leukocyte infiltration occurs in a mouse model of
      permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or
      24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral
      artery occlusion (MCAO). Using flow cytometry, we observed ~15,000 leukocytes
      (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after
      permanent MCAO (pMCAO), comprising ~40% lymphoid cells and ~60% myeloid cells.
      Neutrophils were the predominant cell type entering the brain, and were increased
      to ~5,000 as early as 3 hours after pMCAO. Several cell types (monocytes,
      macrophages, B lymphocytes, CD8(+) T lymphocytes, and natural killer cells) were
      also increased at 3 hours to levels sustained for 24 hours, whereas others
      (CD4(+) T cells, natural killer T cells, and dendritic cells) were unchanged at 3
      hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis
      revealed that leukocytes typically had entered and widely dispersed throughout
      the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO,
      there were ~50% fewer infiltrating leukocytes at 24 hours after transient MCAO
      (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally
      increased in both models. These findings indicate that a profound infiltration of
      inflammatory cells occurs in the brain early after focal ischemia, especially
      without reperfusion. 

PMID- 24326389
TI  - Glycolysis and oxidative phosphorylation in neurons and astrocytes during network
      activity in hippocampal slices.
AB  - Network activation triggers a significant energy metabolism increase in both
      neurons and astrocytes. Questions of the primary neuronal energy substrate (e.g.,
      glucose vs. lactate) as well as the relative contributions of glycolysis and
      oxidative phosphorylation and their cellular origin (neurons vs. astrocytes) are
      still a matter of debates. Using simultaneous measurements of
      electrophysiological and metabolic parameters during synaptic stimulation in
      hippocampal slices from mature mice, we show that neurons and astrocytes use both
      glycolysis and oxidative phosphorylation to meet their energy demands.
      Supplementation or replacement of glucose in artificial cerebrospinal fluid
      (ACSF) with pyruvate or lactate strongly modifies parameters related to network
      activity-triggered energy metabolism. These effects are not induced by changes in
      ATP content, pH(i), [Ca(2+)](i) or accumulation of reactive oxygen species. Our
      results suggest that during network activation, a significant fraction of NAD(P)H
      response (its overshoot phase) corresponds to glycolysis and the changes in
      cytosolic NAD(P)H and mitochondrial FAD are coupled. Our data do not support the
      hypothesis of a preferential utilization of astrocyte-released lactate by neurons
      during network activation in slices--instead, we show that during such activity
      glucose is an effective energy substrate for both neurons and astrocytes.

PMID- 24326390
TI  - Hydrocephalus after intraventricular hemorrhage: the role of thrombin.
AB  - Previous studies demonstrated that thrombin is an important factor in brain
      injury after intracerebral hemorrhage. This study investigated the effect of
      thrombin on hydrocephalus development in a rat intraventricular hemorrhage (IVH)
      model. There were three parts in this study. First, male Sprague-Dawley rats had
      an injection of 200 MUL saline, autologous blood or heparinized blood, into the
      right lateral ventricle. Second, rats had an injection of 50 MUL saline or 3U
      thrombin into the right lateral ventricle. Third, rats had an injection of
      thrombin (3U) with a protease-activated receptor-1 (PAR-1) antagonist, SCH79797
      (0.15 nmol), or vehicle into the right lateral ventricle. Lateral ventricle
      volumes were measured by magnetic resonance imaging and the brains were used for
      immunohistochemistry and western blot analyses. Intraventricular injection of
      autologous blood induced hydrocephalus from day 1 to 28. Heparinized blood
      injection resulted in less hydrocephalus at all time points compared with blood
      injection alone (P<0.05). Intraventricular injection of thrombin caused
      significant hydrocephalus, ventricular wall damage, and periventricular blood
      brain barrier disruption. Thrombin-induced hydrocephalus was reduced by co
      injection of the PAR-1 antagonist SCH79797 (P<0.05). In conclusion, thrombin
      contributes to hydrocephalus development after IVH and thrombin-induced
      hydrocephalus is through PAR-1. 

PMID- 24326391
TI  - Bradykinin antagonist counteracts the acute effect of both angiotensin-converting
      enzyme inhibition and of angiotensin receptor blockade on the lower limit of
      autoregulation of cerebral blood flow.
AB  - The lower limit of autoregulation of cerebral blood flow (CBF) can be modulated
      with both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor
      blockers (ARB). The influence of bradykinin antagonism on ARB-induced changes was
      the subject of this study. CBF was measured in Sprague-Dawley rats with laser
      Doppler technique. The blood pressure was lowered by controlled bleeding. Six
      groups of rats were studied: a control group and five groups given drugs
      intravenously: an ACE inhibitor (enalaprilat), an ARB (candesartan), a bradykinin
      2 receptor antagonist (Hoe 140), a combination of enalaprilat and Hoe 140, and a
      combination of candesartan and Hoe 140. In the control group, the lower limit of
      CBF autoregulation was 54+/-9 mm Hg (mean+/-s.d.), with enalaprilat it was 46+/
      6, with candesartan 39+/-8, with Hoe 140 53+/-6, with enalaprilat/Hoe 140 52+/-6,
      and with candesartan/Hoe 140 50+/-7. Both enalaprilat and candesartan lowered the
      lower limit of autoregulation of CBF significantly. The bradykinin antagonist
      abolished not only the effect of the ACE inhibitor but surprisingly also the
      effect of the ARB on the lower limit of CBF autoregulation, the latter suggesting
      an effect on intravascular bradykinin. 

PMID- 24326392
TI  - Transplantation of neural stem cells that overexpress SOD1 enhances amelioration
      of intracerebral hemorrhage in mice.
AB  - Previous studies have shown that intraparenchymal transplantation of neural stem
      cells (NSCs) ameliorates neurologic deficits in animals with intracerebral
      hemorrhage (ICH). However, massive grafted cell death after transplantation,
      possibly caused by a hostile host brain environment, lessens the effectiveness of
      this approach. We focused on the effect of oxidative stress against grafted NSCs
      and hypothesized that conferring antioxidant properties to transplanted NSCs may
      overcome their death and enhance neuroprotection after ICH. Copper/zinc
      superoxide dismutase (SOD1) is a specific antioxidant enzyme that counteracts
      superoxide anions. We investigated whether genetic manipulation to overexpress
      SOD1 enhances survival of grafted NSCs and accelerates amelioration of ICH.
      Neural stem cells that overexpress SOD1 were administered intracerebrally 3 days
      after ICH in a mouse model. Histologic and behavioral tests were examined after
      ICH. Copper/zinc-superoxide dismutase overexpression protected the grafted NSCs
      via a decrease in production of reactive oxygen species. This resulted in an
      increase in paracrine factors released by the NSCs, and an increase in surviving
      neurons in the striatum and a reduction in striatal atrophy. In addition, SOD1
      overexpression showed progressive improvement in behavioral recovery. Our results
      suggest that enhanced antioxidative activity in NSCs improves efficacy of stem
      cell therapy for ICH. 

PMID- 24326394
TI  - Analysis of spatiotemporal pattern correction using a computational model of the
      auditory periphery.
AB  - OBJECTIVES: The purpose of this study was to determine the cause of poor
      experimental performance of a spatiotemporal pattern correction (SPC) scheme that
      has been proposed as a hearing aid algorithm and to determine contexts in which
      it may provide benefit. The SPC scheme is intended to compensate for altered
      phase response and group delay differences in the auditory nerve spiking patterns
      in impaired ears. Based on theoretical models of loudness and the hypothesized
      importance of temporal fine structure for intelligibility, the compensations of
      the SPC scheme are expected to provide benefit; however, preliminary experiments
      revealed that listeners preferred unprocessed or minimally processed speech as
      opposed to complete SPC processed speech. DESIGN: An improved version of the SPC
      scheme was evaluated with a computational auditory model in response to a
      synthesized vowel at multiple SPLs. The impaired model auditory nerve response to
      SPC-aided stimuli was compared to the unaided stimuli for spectrotemporal
      response similarity to the healthy auditory model. This comparison included
      analysis of synchronized rate across auditory nerve characteristic frequencies
      and a measure of relative phase response of auditory nerve fibers to complex
      stimuli derived from cross-correlations. RESULTS: Analysis indicates that SPC can
      improve a metric of relative phase response at low SPLs, but may do so at the
      cost of decreased spectrotemporal response similarity to the healthy auditory
      model and degraded synchrony to vowel formants. In-depth analysis identifies
      several technical and conceptual problems associated with SPC that need to be
      addressed. These include the following: (1) a nonflat frequency response through
      the analysis-synthesis filterbank that results from time-varying changes in the
      relative temporal alignment of filterbank channels, (2) group delay corrections
      that are based on incorrect frequencies because of spread of synchrony in
      auditory nerve responses, and (3) frequency modulations in the processed signal
      created by the insertion of delays. CONCLUSIONS: Despite these issues, SPC
      provided benefit to an error metric derived from auditory nerve response cross
      correlations at low SPLs, which may mean phase adjustment is achieved at the
      expense of other metrics, but could be beneficial for low-level speech.

PMID- 24326393
TI  - Aneurysmal remodeling in the circle of Willis after carotid occlusion in an
      experimental model.
AB  - Carotid occlusions are associated with de novo intracranial aneurysm formation in
      clinical case reports, but this phenomenon is not widely studied. We performed
      bilateral carotid ligation (n=9) in rabbits to simulate carotid occlusion, and
      sham surgery (n=3) for control. Upon euthanasia (n=3 at 5 days, n=6 at 6 months
      post ligation, and n=3 at 5 days after sham operation), vascular corrosion casts
      of the circle of Willis (CoW) were created. Using scanning electron microscopy,
      we quantified gross morphologic, macroscopic, and microscopic changes on the
      endocasts and compared findings with histologic data. At 5 days, CoW arteries of
      ligated animals increased caliber. The posterior communicating artery (PCom)
      increased length and tortuosity, and the ophthalmic artery (OA) origin presented
      preaneurysmal bulges. At 6 months, calibers were unchanged from 5 days, PComs
      further increased tortuosity while presenting segmental dilations, and the OA
      origin and basilar terminus presented preaneurysmal bulges. This exploratory
      study provides evidence that flow increase after carotid occlusion produces both
      compensatory arterial augmentation and pathologic remodeling such as tortuosity
      and saccular/fusiform aneurysm. Our findings may have considerable clinical
      implications, as these lesser-known consequences should be considered when
      managing patients with carotid artery disease or choosing carotid ligation as a
      therapeutic option. 

PMID- 24326397
TI  - Surface plasmon resonance-induced color-selective Au-peapodded silica nanowire
      photodetectors with high photoconductive gain.
AB  - We report the optoelectronic device properties of individual Au-silica hybrid
      nanowires prepared by microwave plasma enhanced chemical vapor deposition. Due to
      the surface plasmon resonance (SPR) effect the photo-responsivity peak strongly
      depends on the shape of the embedded gold nanostructures in the silica nanowire
      in which the shape can be modified by controlling the growth time of Au-silica
      nanowires. Finite difference time domain (FDTD) simulation shows that the
      electric field distribution profiles of Au-silica hybrid nanowires support the
      photo-responsivity spectrum results. The photodetector performance of the Au
      NPs@silica nanowire is investigated. The single Au-NPs@silica nanowire exhibits
      unique photo-responsivity in the visible range (500 nm), high selectivity, high
      photoconductive gain, and very fast rise (141 MUs) and decay (298 MUs) time
      constants. Furthermore, the mechanism for the high photoconductive gain is also
      discussed. This result implies that the Au-NPs@silica nanowire can be applied for
      future nanoscale optoelectronic devices. 

PMID- 24326396
TI  - Dietary supplementation of polyunsaturated fatty acids in Caenorhabditis elegans.
AB  - Fatty acids are essential for numerous cellular functions. They serve as
      efficient energy storage molecules, make up the hydrophobic core of membranes,
      and participate in various signaling pathways. Caenorhabditis elegans synthesizes
      all of the enzymes necessary to produce a range of omega-6 and omega-3 fatty
      acids. This, combined with the simple anatomy and range of available genetic
      tools, make it an attractive model to study fatty acid function. In order to
      investigate the genetic pathways that mediate the physiological effects of
      dietary fatty acids, we have developed a method to supplement the C. elegans diet
      with unsaturated fatty acids. Supplementation is an effective means to alter the
      fatty acid composition of worms and can also be used to rescue defects in fatty
      acid-deficient mutants. Our method uses nematode growth medium agar (NGM)
      supplemented with fatty acid sodium salts. The fatty acids in the supplemented
      plates become incorporated into the membranes of the bacterial food source, which
      is then taken up by the C. elegans that feed on the supplemented bacteria. We
      also describe a gas chromatography protocol to monitor the changes in fatty acid
      composition that occur in supplemented worms. This is an efficient way to
      supplement the diets of both large and small populations of C. elegans, allowing
      for a range of applications for this method.

PMID- 24326395
TI  - The effects of ketamine and risperidone on eye movement control in healthy
      volunteers.
AB  - The non-competitive N-methyl-D-aspartate receptor antagonist ketamine leads to
      transient psychosis-like symptoms and impairments in oculomotor performance in
      healthy volunteers. This study examined whether the adverse effects of ketamine
      on oculomotor performance can be reversed by the atypical antipsychotic
      risperidone. In this randomized double-blind, placebo-controlled study, 72
      healthy participants performed smooth pursuit eye movements (SPEM), prosaccades
      (PS) and antisaccades (AS) while being randomly assigned to one of four drug
      groups (intravenous 100 ng ml(-1) ketamine, 2 mg oral risperidone, 100  ng ml(-1)
      ketamine plus 2 mg oral risperidone, placebo). Drug administration did not lead
      to harmful adverse events. Ketamine increased saccadic frequency and decreased
      velocity gain of SPEM (all P < 0.01) but had no significant effects on PS or AS
      (all P > or = 0.07). An effect of risperidone was observed for amplitude gain and
      peak velocity of PS and AS, indicating hypometric gain and slower velocities
      compared with placebo (both P < or = 0.04). No ketamine by risperidone
      interactions were found (all P > or = 0.26). The results confirm that the
      administration of ketamine produces oculomotor performance deficits similar in
      part to those seen in schizophrenia. The atypical antipsychotic risperidone did
      not reverse ketamine-induced deteriorations. These findings do not support the
      cognitive enhancing potential of risperidone on oculomotor biomarkers in this
      model system of schizophrenia and point towards the importance of developing
      alternative performance-enhancing compounds to optimise pharmacological treatment
      of schizophrenia.

PMID- 24326398
TI  - Primary stability of two uncementedacetabular components of different geometry:
      hemispherical or peripherallyenhanced?
AB  - OBJECTIVE: This study compared the primary stability of two commercially
      available acetabular components from the same manufacturer, which differ only in
      geometry; a hemispherical and a peripherally enhanced design (peripheral self
      locking (PSL)). The objective was to determine whether altered geometry resulted
      in better primary stability. METHODS: Acetabular components were seated with 0.8
      mm to 2 mm interference fits in reamed polyethylene bone substrate of two
      different densities (0.22 g/cm(3) and 0.45 g/cm(3)). The primary stability of
      each component design was investigated by measuring the peak failure load during
      uniaxial pull-out and tangential lever-out tests. RESULTS: There was no
      statistically significant difference in seating force (p = 0.104) or primary
      stability (pull-out p = 0.171, lever-out p = 0.087) of the two components in the
      low-density substrate. Similarly, in the high-density substrate, there was no
      statistically significant difference in the peak pull-out force (p = 0.154) or
      lever-out moment (p = 0.574) between the designs. However, the PSL component
      required a significantly higher seating force than the hemispherical cup in the
      high-density bone analogue (p = 0.006). CONCLUSIONS: Higher seating forces
      associated with the PSL design may result in inadequate seating and increased
      risk of component malpositioning or acetabular fracture in the intra-operative
      setting in high-density bone stock. Our results, if translated clinically,
      suggest that a purely hemispherical geometry may have an advantage over a
      peripherally enhanced geometry in high density bone stock. Cite this article:
      Bone Joint Res 2013;2:264-9.

PMID- 24326399
TI  - Imaging for approach selection of TAVI: assessment of the aorto-iliac tract
      diameter by computed tomography-angiography versus projection angiography.
AB  - The choice of preferred access route for transcatheter aortic valve implantation
      (TAVI) is mainly guided by the minimal aorto-femoral tract diameter. Currently,
      projection angiography (XA) and CT-angiography (CTA) are used interchangeably to
      assess this diameter in the TAVI work-up. We aimed to assess the agreement of XA
      and CTA diameter measurements in TAVI candidates. Diameters of 700 aorta-iliac
      segments of 102 TAVI candidates were analyzed on both XA and CTA. The diameters
      on XA were measured manually, for the CTA-based analysis semi-automated
      segmentation software was used. Paired sample T test was used to evaluate
      differences in diameter measurements between the modalities. Disagreement on the
      suitability for a transfemoral (TF)-TAVI approach was identified. The
      interobserver agreement for both measurements was assessed by calculating the
      intraclass correlation coefficient (ICC). The average diameters were 10.1 +/- 1.8
      mm and 8.4 +/- 1.7 for XA and CTA respectively. The mean paired difference was
      1.73 mm (p < 0.001). For 18 patients (17.6 %) diameters measured on CTA images,
      were bilaterally less than 6 mm, whilst XA indicated a minimum diameter exceeding
      6 mm. For both modalities, the interobserver agreement was excellent (ICC 0.95).
      Diameters measured semi-automatically on CTA were statistically significantly
      smaller compared to XA. This should be acknowledged in the work-up for selecting
      the most appropriate approach for TAVI. In our population 17.6 % of patients
      would have been denied a transfemoral TAVI based on CTA measurements, whilst XA
      suggested diameters sufficient for a TF approach.

PMID- 24326402
TI  - The enhancement debate.

PMID- 24326400
TI  - Forebrain-specific CRF overproduction during development is sufficient to induce
      enduring anxiety and startle abnormalities in adult mice.
AB  - Corticotropin releasing factor (CRF) regulates physiological and behavioral
      responses to stress. Trauma in early life or adulthood is associated with
      increased CRF in the cerebrospinal fluid and heightened anxiety. Genetic variance
      in CRF receptors is linked to altered risk for stress disorders. Thus, both
      heritable differences and environmentally induced changes in CRF
      neurotransmission across the lifespan may modulate anxiety traits. To test the
      hypothesis that CRF hypersignaling is sufficient to modify anxiety-related
      phenotypes (avoidance, startle, and conditioned fear), we induced transient
      forebrain-specific overexpression of CRF (CRFOE) in mice (1) during development
      to model early-life stress, (2) in adulthood to model adult-onset stress, or (3)
      across the entire postnatal lifespan to model heritable increases in CRF
      signaling. The consequences of these manipulations on CRF peptide levels and
      behavioral responses were examined in adulthood. We found that transient CRFOE
      during development decreased startle habituation and prepulse inhibition, and
      increased avoidance (particularly in females) recapitulating the behavioral
      effects of lifetime CRFOE despite lower CRF peptide levels at testing. In
      contrast, CRFOE limited to adulthood reduced contextual fear learning in females
      and increased startle reactivity in males but did not change avoidance or startle
      plasticity. These findings suggest that forebrain CRFOE limited to development is
      sufficient to induce enduring alterations in startle plasticity and anxiety,
      while forebrain CRFOE during adulthood results in a different phenotype profile.
      These findings suggest that startle circuits are particularly sensitive to
      forebrain CRFOE, and that the impact of CRFOE may be dependent on the time of
      exposure. 

PMID- 24326404
TI  - Selective detection of complementarity-determining regions of monoclonal antibody
      by limiting protease access to the substrate: nano-surface and molecular
      orientation limited proteolysis.
AB  - We report a novel method for the selective proteolysis by limiting protease
      access to the substrate, which we have named nano-surface and molecular
      orientation limited (nSMOL) proteolysis. We focus on the identification of the
      Fab and quantitation of antibodies. This method successfully performed limited
      proteolysis on the Fab. 

PMID- 24326406
TI  - Impact of a Pharmacist on Compliance With Hospital Core Measures.
AB  - PURPOSE: The role of a pharmacist in achieving compliance with hospital core
      measures is described. SUMMARY: Core measures for hospitals, also known as
      quality measures, were introduced by the Department of Health and Human Services
      as an initiative to improve health care through accountability and public
      disclosure. Hospitals receive financial incentives for compliance with these core
      measures, but most importantly, these measures ensure that evidence-based therapy
      is consistently provided to each patient. If a core measure is not met,
      documentation must be provided to ensure that there is not a failure to meet the
      measure. Pharmacists were granted the authority to provide core measure
      documentation in 2007. There are a total of 44 core measures, 22 (50%) of which
      are medication related and can be documented by a pharmacist. Over a 5-year
      period, clinical pharmacists have recorded 1281 interventions for core measure
      documentation. In an analysis of a 1-year period of charts with missing core
      measure documentation, pharmacists prevented failure to meet the measure in 96%
      of the cases. CONCLUSION: Given the great impact that pharmacists can have on
      hospital core measure compliance, each hospital's Pharmacy Department should
      evaluate ways to improve involvement in the quality programs at their hospitals.

PMID- 24326405
TI  - Carbonic anhydrase activity of dinuclear Cu(II) complexes with patellamide model
      ligands.
AB  - The dicopper(II) complexes of six pseudo-octapeptides, synthetic analogues of
      ascidiacyclamide and the patellamides, found in ascidians of the Pacific and
      Indian Oceans, are shown to be efficient carbonic anhydrase model complexes with
      k(cat) up to 7.3 * 10(3) s(-1) (uncatalyzed: 3.7 * 10(-2) s(-1); enzyme
      catalyzed: 2 * 10(5)-1.4 * 10(6) s(-1)) and a turnover number (TON) of at least
      1700, limited only by the experimental conditions used. So far, no copper-based
      natural carbonic anhydrases are known, no faster model systems have been
      described and the biological role of the patellamide macrocycles is so far
      unknown. The observed CO2 hydration rates depend on the configuration of the
      isopropyl side chains of the pseudo-octapeptide scaffold, and the naturally
      observed R*,S*,R*,S* geometry is shown to lead to more efficient catalysts than
      the S*,S*,S*,S* isomers. The catalytic efficiency also depends on the
      heterocyclic donor groups of the pseudo-octapeptides. Interestingly, the
      dicopper(II) complex of the ligand with four imidazole groups is a more efficient
      catalyst than that of the close analogue of ascidiacyclamide with two thiazole
      and two oxazoline rings. The experimental observations indicate that the
      nucleophilic attack of a Cu(II)-coordinated hydroxide at the CO2 carbon center is
      rate determining, i.e. formation of the catalyst-CO2 adduct and release of
      carbonate/bicarbonate are relatively fast processes.

PMID- 24326407
TI  - Pharmacist testers in multidisciplinary health care team expand HIV point-of-care
      testing program.
AB  - Knowledge of HIV serostatus is the first step to accessing treatment, reducing
      transmission, and mitigating public health challenges. We describe the expansion
      of an HIV point-of-care testing (POCT) program within a health care system
      utilizing pharmacists as testers. The testing program's expansion is detailed and
      its impact assessed. The POCT program was evaluated by comparing the number of
      traditional HIV venipuncture tests to the number of POCTs performed across the
      health system as well as comparing the number of POCTs performed by clinical
      pharmacists to the number of tests at other POCT locations. Although pharmacists'
      contributions to HIV prevention are well documented, pharmacists' involvement in
      HIV testing initiatives is still nascent. Our POCT program demonstrates an
      effective HIV testing initiative driven by pharmacists and other health care
      providers. 

PMID- 24326408
TI  - Intensive care unit delirium: a review of the literature.
AB  - PURPOSE: The recent literature regarding intensive care unit (ICU) delirium and
      updated clinical practice guidelines are reviewed. SUMMARY: Recent studies show
      that ICU delirium in critically ill patients is an independent predictor of
      higher mortality, longer ICU and hospital stay, and is associated with multiple
      clinical complications. Delirium has been reported to occur in greater than 80%
      of hospitalized critically ill patients, yet it remains an underdiagnosed
      condition. Several subtypes of delirium have been identified including
      hypoactive, hyperactive, and mixed presentation. Although the exact mechanism is
      unknown, several factors are thought to interact to cause delirium. Multiple risk
      factors related to medications, acute illness, the environment, and patient
      characteristics may contribute to the development of delirium. Practical bedside
      screening tools have been validated and are recommended to identify ICU patients
      with delirium. Nonpharmacologic interventions such as early mobilization have
      resulted in better functional outcomes, decreased incidence and duration of
      delirium, and more ventilator-free days. Data supporting pharmacologic treatments
      are limited. CONCLUSION: Clinicians should become familiar with tools to identify
      delirium in order to initiate treatment and remove mitigating factors early in
      hospitalization to prevent delirium. Pharmacists are in a unique position to
      reduce delirium through minimization of medication-related risk factors and
      development of protocols.

PMID- 24326409
TI  - Safety of compounded calcium chloride admixtures for peripheral intravenous
      administration in the setting of a calcium gluconate shortage.
AB  - Calcium gluconate is preferred over calcium chloride for intravenous (IV)
      repletion of calcium deficiencies in the inpatient setting. In the setting of a
      national shortage of IV calcium gluconate, our institution implemented a
      compounded calcium chloride admixture for IV administration. The objective of
      this analysis is to evaluate the peripheral infusion site safety of compounded IV
      calcium chloride admixtures in adult inpatients. A total of 222 patients,
      encompassing 224 inpatient admissions, from April to June 2011 were
      retrospectively reviewed. Sterile preparations of calcium chloride in 5% dextrose
      (600 mg/250 mL and 300 mg/100 mL) were used during the study time period. Adverse
      infusion site reactions were assessed using an institutional infiltration and
      phlebitis grading system. A total of 333 doses were administered peripherally. In
      all, 4 (1.8%) patients experienced a moderate to severe infusion site reaction,
      with 3 due to phlebitis and 1 due to infiltration. Naranjo Nomogram for Adverse
      Drug Reaction Assessment classified all 4 reactions to have a possible link to
      calcium chloride administration. Peripheral administration of compounded calcium
      chloride admixtures in 5% dextrose is associated with a low incidence of IV
      infusion site reactions and can be considered as an alternative in the event of a
      calcium gluconate shortage. 

PMID- 24326410
TI  - Community-Based Pharmacists' Needs for HIV-Related Training and Experience.
AB  - OBJECTIVE: To examine pharmacists' self-reported competence in providing care to
      persons living with HIV (PLWH) and their HIV-related training and experience
      needs. METHODS: We interviewed 28 community-based pharmacists providing care to
      PLWH in 4 Midwestern cities. RESULTS: Less than half (46%) of the pharmacists
      considered themselves competent to provide PLWH care, and less than a third (29%)
      worked with PLWH during their pharmacy residency. Specialty pharmacists need
      training on opportunistic infections and HIV-related comorbidities, nonspecialty
      pharmacists need general training in HIV treatment and patient communications
      skills, and all pharmacists require a mechanism to keep updated in the latest HIV
      treatment recommendations. CONCLUSION: In the current era of patient-centered
      care, a pharmacist that is well rounded-not just in dispensing antiretroviral
      medications but highly knowledgeable in different aspects of ART and HIV-specific
      patient care-can make a valuable contribution to the health care team. Pharmacy
      school curricula and continuing professional education need to be aligned to meet
      the knowledge and competency needs of community pharmacists who are strategically
      positioned to provide care to PLWH.

PMID- 24326411
TI  - Development of an anticoagulation stewardship program at a large tertiary care
      academic institution.
AB  - Pharmacist-directed anticoagulation management services (AMSs) have been shown to
      significantly lower anticoagulation-related mortality, length of hospital stay,
      bleeding complications, blood transfusion requirements, and cost of therapy. AMSs
      are only 1 component of an anticoagulation stewardship program. Frequently,
      stewardship programs are limited to inpatient populations. Incorporating
      components that facilitate transition to outpatient status will ideally encompass
      complete care. The purpose of this program was to expand anticoagulation services
      and standardize care by implementing a full-service stewardship program including
      a transition of care service. The first component of the study involved
      medication surveillance for inpatients on anticoagulation therapy. The second
      component involved transitioning patients on anticoagulation, primarily with
      venous thromboembolism (VTE) to outpatient management. Finally, the pharmacist
      identified areas for optimization. Optimization involved developing or updating
      protocols to reflect updates in the literature as well as updating institution
      specific information resources. Interventions made through medication
      surveillance and utilization of the VTE transition of care services translated
      into a total cost savings of approximately US$270 320. A postgraduate, first-year
      pharmacy resident contributed to improving patient outcomes while reducing
      utilization of hospital services and obtaining substantial cost savings through
      participation in anticoagulation stewardship services. 

PMID- 24326412
TI  - Management of prediabetes: a comparison of the treatment approaches utilized by a
      family practice clinic and an internal medicine/endocrinology practice.
AB  - PURPOSE: To compare the management of prediabetes between a family practice
      clinic and internal medicine/endocrinology practice. METHODS: A randomized,
      retrospective evaluation of the medical history in 168 eligible patients with a
      diagnosis of prediabetes or abnormal blood glucose (BG) at a family practice
      clinic (n = 78) and an internal medicine/endocrinology practice (n = 90).
      RESULTS: The internal medicine/endocrinology practice provided more counseling
      regarding lifestyle modifications (91.1% vs 76.9%, P = .039), specific physical
      activity recommendations (26.7% vs 7.7%, P = .003), and recommended more patients
      receive 150 minutes/week of moderate exercise (8.9% vs 1.3%, P = .038). The
      family practice clinic provided more written dietary information (16.9% vs 13.3%,
      P = .044) and specific weight loss goals (20.5% vs 6.7%, P = .015). The internal
      medicine/endocrinology practice initiated pharmacological therapy in more
      patients (51.1% vs 3.8%, P< .001) and had a significant decrease in fasting BG
      from baseline compared to the family practice clinic (-9.0 vs -5.6 mg/dL, P<
      .001). CONCLUSION: Providers are likely to initiate nonpharmacological therapy
      but may not provide specific education recommended by the American Diabetes
      Association. The integration of a multidisciplinary team to provide guideline
      based nonpharmacologic counseling may be beneficial in improving outcomes in the
      management of prediabetes.

PMID- 24326413
TI  - Paraoxonase activity and genetic polymorphisms in northern Han Chinese workers
      exposed to organophosphate pesticides.
AB  - Paraoxonase (PON1) is one of the major players in the detoxification of
      organophosphates (OPs). This study presents our investigation into the effect of
      OPs on serum PON1 activity and the distribution of common PON1 polymorphisms in
      Han Chinese workers with repeated high exposure to OP pesticides, and the factors
      modulating PON1 activity. In all, 400 participants, including 180 workers exposed
      to OP pesticides occupationally, and 220 controls were investigated. Serum PON1
      and cholinesterase (ChE) activity were measured, and genotyping was done using
      polymerase chain reaction-restriction fragment length polymorphism. The
      association between PON1 activity and PON1 polymorphisms, and the influencing
      factors of PON1 activity, were analyzed. The results revealed that repeated OP
      exposures significantly decreased serum PON1 and ChE activity (P< 0.05), although
      the exposed workers did not complain of health problems. Higher L and R allele
      frequencies for the L55M and Q192R polymorphisms of PON1 were observed. PON1
      polymorphisms (especially the Q192R polymorphism) and pesticide exposures
      significantly affected serum PON1 activity in the study population. Therefore,
      the results of this investigation indicate PON1 polymorphisms and pesticide
      exposures may be important risk predictors for OP poisoning in the Han Chinese
      population, who display very high frequencies of the M allele and R allele for
      PON1 polymorphisms at the positions 55 and 192, respectively.

PMID- 24326414
TI  - Characterization of cultured multipotent zebrafish neural crest cells.
AB  - The neural crest is a unique cell population associated with vertebrate
      evolution. Neural crest cells (NCCs) are characterized by their multipotent and
      migratory potentials. While zebrafish is a powerful genetic model organism, the
      isolation and culture of zebrafish NCCs would provide a useful adjunct to fully
      interrogate the genetic networks that regulate NCC development. Here we report
      for the first time the isolation, in vitro culture, and characterization of NCCs
      from zebrafish embryos. NCCs were isolated from transgenic sox10:egfp embryos
      using fluorescence activated cell sorting and cultured in complex culture medium
      without feeder layers. NCC multilineage differentiation was determined by
      immunocytochemistry and real-time qPCR, cell migration was assessed by wound
      healing assay, and the proliferation index was calculated by immunostaining
      against the mitosis marker phospho-histone H3. Cultured NCCs expressed major
      neural crest lineage markers such as sox10, sox9a, hnk1, p75, dlx2a, and pax3,
      and the pluripotency markers c-myc and klf4. We showed that the cultured NCCs can
      be differentiated into multiple neural crest lineages, contributing to neurons,
      glial cells, smooth muscle cells, melanocytes, and chondrocytes. We applied the
      NCC in vitro model to study the effect of retinoic acid on NCC development. We
      showed that retinoic acid had a profound effect on NCC morphology and
      differentiation, significantly inhibited proliferation and enhanced cell
      migration. The availability of high numbers of NCCs and reproducible functional
      assays offers new opportunities for mechanistic studies of neural crest
      development, in genetic and chemical biology applications. 

PMID- 24326415
TI  - Detection of rotateq vaccine-derived, double-reassortant rotavirus in a 7-year
      old child with acute gastroenteritis.
AB  - We describe a case of acute gastroenteritis in a schoolgirl associated with a
      detection of vaccine-derived, human-bovine double reassortant G1P[8] rotavirus,
      without any known contact with recently vaccinated infants. We propose that human
      bovine double reassortant G1P[8] may be formed in RotaTeq-vaccinated infants and
      can occasionally cause gastroenteritis symptoms in vaccine recipients who may
      rarely transmit the virus to close contacts. The present case suggests that such
      viruses can remain stable in environment longer than 1 transmission cycle. 

PMID- 24326416
TI  - The changing epidemiology of serious bacterial infections in young infants.
AB  - BACKGROUND: Management of febrile young infants suspected of having serious
      bacterial infections has been a challenge for decades. The impact of changes in
      prenatal screening for Group B Streptococcus and of infant immunizations has
      received little attention in population-based studies. METHODS: This study
      analyzed all cultures of blood, urine and cerebrospinal fluid obtained from full
      term infants 1 week to 3 months of age, who presented for care at Kaiser
      Permanente Northern California during a 7-year period utilizing electronic
      medical records. RESULTS: A total of 224,553 full-term infants were born during
      the study period. Of 5396 blood cultures, 129 bacteremic infants were identified
      (2%). Of 4599 urine cultures, 823 episodes of urinary tract infection (UTI) were
      documented in 778 infants (17%). Of 1796 CSF cultures, 16 infants had bacterial
      meningitis (0.9%). The incidence rate of serious bacterial infections
      (bacteremia, UTI and meningitis) and febrile serious bacterial infections was
      3.75 and 3.1/1000 full-term births, respectively. Escherichia coli was the
      leading cause of bacteremia (78), UTI (719) and bacterial meningitis (7). There
      were 23 infants with Group B Streptococcus bacteremia including 6 cases of
      meningitis and no cases of Listeria infection. Nine percentage of infants had
      multiple sites of infection; 10% of UTIs were associated with bacteremia and 52%
      of bacteremia was associated with UTI. CONCLUSIONS: Compared with earlier
      studies, UTIs now are found significantly more often than bacteremia and
      meningitis with 92% of occult infections associated with UTIs. These data
      emphasize the importance of an urinalysis in febrile infants.

PMID- 24326417
TI  - Characterization of an animal model of pregnancy-induced vitamin D deficiency due
      to metabolic gene dysregulation.
AB  - Vitamin D deficiency has been associated with pregnancy complications such as
      preeclampsia, gestational diabetes, and recurrent miscarriage. Therefore, we
      hypothesized differences in vitamin D status between healthy [Sprague-Dawley (SD)
      and Lewis (LW)] and complicated [Brown Norway (BN)] rat pregnancies. In SD, LW,
      and BN rats, we analyzed the maternal plasma levels of the vitamin D metabolites
      25-OH-D and 1,25-(OH)2-D at prepregnancy, pregnancy, and postpartum. Analysis of
      the active metabolite 1,25-(OH)2-D showed a twofold increase in pregnant SD and
      LW rats but a nearly 10-fold decrease in pregnant BN rats compared with
      nonpregnant controls. BN rats had a pregnancy-dependent upregulation of CYP24a1
      expression, a key enzyme that inactivates vitamin D metabolites. In contrast, the
      maternal renal expression of CYP24a1 in SD and LW rats remained constant
      throughout pregnancy. Analysis of the vitamin D receptor (VDR) indicated that LW
      and SD but not BN rats experience a pregnancy-induced 10-fold decrease in
      maternal renal VDR protein levels. Further analysis of bisulfite-converted and
      genomic DNA indicated that the observed differences in maternal renal regulation
      of CYP24a1 during pregnancy and lactation are not due to differences in CYP24a1
      promoter methylation or single-nucleotide polymorphisms. Finally, supplementation
      with 1,25-(OH)2-D significantly improved the reproductive phenotype of BN rats by
      increasing litter size and maternal-fetal weight outcomes. We conclude that BN
      rats represent a novel animal model of pregnancy-specific vitamin D deficiency
      that is linked to pregnancy complications. Vitamin D deficiency in BN rats
      correlates with maternal renal CYP24a1 upregulation followed by CYP27b1
      upregulation. 

PMID- 24326418
TI  - Involvement of mast cells in adipose tissue fibrosis.
AB  - Recently, fibrosis is observed in obese adipose tissue; however, the pathogenesis
      remains to be clarified. Obese adipose tissue is characterized by chronic
      inflammation with massive accumulation of immune cells including mast cells. The
      objective of the present study was to clarify the relationship between fibrosis
      and mast cells in obese adipose tissue, as well as to determine the origin of
      infiltrating mast cells. We observed the enhancement of mast cell accumulation
      and fibrosis in adipose tissue of severely obese diabetic db/db mice.
      Furthermore, adipose tissue-conditioned medium (ATCM) from severely obese
      diabetic db/db mice significantly enhanced collagen 5 mRNA expression in NIH-3T3
      fibroblasts, and this enhancement was suppressed by the addition of an anti-mast
      cell protease 6 (MCP-6) antibody. An in vitro study showed that only collagen V
      among various types of collagen inhibited preadipocyte differentiation. Moreover,
      we found that ATCM from the nonobese but not obese stages of db/db mice
      significantly enhanced the migration of bone marrow-derived mast cells (BMMCs).
      These findings suggest that immature mast cells that infiltrate into adipose
      tissue at the nonobese stage gradually mature with the progression of obesity and
      diabetes and that MCP-6 secreted from mature mast cells induces collagen V
      expression in obese adipose tissue, which may contribute to the process of
      adipose tissue fibrosis. Induction of collagen V by MCP-6 might accelerate
      insulin resistance via the suppression of preadipocyte differentiation. 

PMID- 24326419
TI  - Intrinsic circannual regulation of brown adipose tissue form and function in tune
      with hibernation.
AB  - Winter hibernators repeatedly cycle between cold torpor and rewarming supported
      by nonshivering thermogenesis in brown adipose tissue (BAT). In contrast, summer
      animals are homeotherms, undergoing reproduction, growth, and fattening. This
      life history confers variability to BAT recruitment and activity. To address the
      components underlying prewinter enhancement and winter activation, we
      interrogated the BAT proteome in 13-lined ground squirrels among three summer and
      five winter states. We also examined mixed physiology in fall and spring
      individuals to test for ambient temperature and seasonal effects, as well as the
      timing of seasonal transitions. BAT form and function differ circannually in
      these animals, as evidenced by morphology and proteome dynamics. This intrinsic
      pattern distinguished homeothermic groups and early vs. late winter hibernators.
      Homeothermic variation derived from postemergence delay in growth and substrate
      biosynthesis. The heterothermic proteome varied less despite extreme winter
      physiological shifts and was optimized to exploit lipids by enhanced fatty acid
      binding, beta-oxidation, and mitochondrial protein translocation. Surprisingly,
      ambient temperature did not affect the BAT proteome during transition seasons;
      rather, the pronounced summer-winter shift preceded environmental changes and
      phenotypic progression. During fall transition, differential regulation of two
      fatty acid binding proteins provides further evidence of recruitment and
      separates proteomic preparation from successful hibernation. Abundance of FABP4
      correlates with torpor bout length throughout the year, clarifying its potential
      function in hibernation. Metabolically active BAT is a target for treating human
      obesity and metabolic disorders. Understanding the hibernator's extreme and
      seasonally distinct recruitment and activation control strategies offers untapped
      potential to identify novel, therapeutically relevant regulatory pathways. 

PMID- 24326420
TI  - MicroRNA profiling links miR-378 to enhanced adipocyte lipolysis in human cancer
      cachexia.
AB  - Cancer cachexia is associated with pronounced adipose tissue loss due to, at
      least in part, increased fat cell lipolysis. MicroRNAs (miRNAs) have recently
      been implicated in controlling several aspects of adipocyte function. To gain
      insight into the possible impact of miRNAs on adipose lipolysis in cancer
      cachexia, global miRNA expression was explored in abdominal subcutaneous adipose
      tissue from gastrointestinal cancer patients with (n = 10) or without (n = 11)
      cachexia. Effects of miRNA overexpression or inhibition on lipolysis were
      determined in human in vitro differentiated adipocytes. Out of 116 miRNAs present
      in adipose tissue, five displayed distinct cachexia-associated expression
      according to both microarray and RT-qPCR. Four (miR-483-5p/-23a/-744/-99b) were
      downregulated, whereas one (miR-378) was significantly upregulated in cachexia.
      Adipose expression of miR-378 associated strongly and positively with
      catecholamine-stimulated lipolysis in adipocytes. This correlation is most
      probably causal because overexpression of miR-378 in human adipocytes increased
      catecholamine-stimulated lipolysis. In addition, inhibition of miR-378 expression
      attenuated stimulated lipolysis and reduced the expression of LIPE, PLIN1, and
      PNPLA2, a set of genes encoding key lipolytic regulators. Taken together,
      increased miR-378 expression could play an etiological role in cancer cachexia
      associated adipose tissue loss via effects on adipocyte lipolysis. 

PMID- 24326421
TI  - Musculoskeletal and prostate effects of combined testosterone and finasteride
      administration in older hypogonadal men: a randomized, controlled trial.
AB  - Testosterone acts directly at androgen receptors and also exerts potent actions
      following 5alpha-reduction to dihydrotestosterone (DHT). Finasteride (type II
      5alpha-reductase inhibitor) lowers DHT and is used to treat benign prostatic
      hyperplasia. However, it is unknown whether elevated DHT mediates either
      beneficial musculoskeletal effects or prostate enlargement resulting from higher
      than-replacement doses of testosterone. Our purpose was to determine whether
      administration of testosterone plus finasteride to older hypogonadal men could
      produce musculoskeletal benefits without prostate enlargement. Sixty men aged
      >=60 yr with a serum testosterone concentration of <=300 ng/dl or bioavailable
      testosterone <=70 ng/dl received 52 wk of treatment with testosterone enanthate
      (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using
      a 2 * 2 factorial design. Over the course of 12 mo, TE increased upper and lower
      body muscle strength by 8-14% (P = 0.015 to <0.001), fat-free mass 4.04 kg (P =
      0.032), lumbar spine bone mineral density (BMD) 4.19% (P < 0.001), and total hip
      BMD 1.96% (P = 0.024) while reducing total body fat -3.87 kg (P < 0.001) and
      trunk fat -1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased
      hematocrit 4.13% (P < 0.001). Coadministration of finasteride did not alter any
      of these effects. Over 12 mo, testosterone also increased prostate volume 11.4
      cm(3) (P = 0.0051), an effect that was completely prevented by finasteride (P =
      0.0027). We conclude that a higher-than-replacement TE combined with finasteride
      significantly increases muscle strength and BMD and reduces body fat without
      causing prostate enlargement. These results demonstrate that elevated DHT
      mediates testosterone-induced prostate enlargement but is not required for
      benefits in musculoskeletal or adipose tissue. 

PMID- 24326422
TI  - Suppression of the GLUT4 adaptive response to exercise in fructose-fed rats.
AB  - Exercise-induced increase in skeletal muscle GLUT4 expression is associated with
      hyperacetylation of histone H3 within a 350-bp DNA region surrounding the myocyte
      enhancer factor 2 (MEF2) element on the Glut4 promoter and increased binding of
      MEF2A. Previous studies have hypothesized that the increase in MEF2A binding is a
      result of improved accessibility of this DNA segment. Here, we investigated the
      impact of fructose consumption on exercise-induced GLUT4 adaptive response and
      directly measured the accessibility of the above segment to nucleases. Male
      Wistar rats (n = 30) were fed standard chow or chow + 10% fructose or
      maltodextrin drinks ad libitum for 13 days. In the last 6 days five animals per
      group performed 3 * 17-min bouts of intermittent swimming daily and five remained
      untrained. Triceps muscles were harvested and used to measure 1) GLUT4, pAMPK,
      and HDAC5 contents by Western blot, 2) accessibility of the DNA segment from
      intact nuclei using nuclease accessibility assays, 3) acetylation level of
      histone H3 and bound MEF2A by ChIP assays, and 4) glycogen content. Swim training
      increased GLUT4 content by ~66% (P < 0.05) but fructose and maltodextrin feeding
      suppressed the adaptation. Accessibility of the DNA region to MNase and DNase I
      was significantly increased by swimming (~2.75- and 5.75-fold, respectively) but
      was also suppressed in trained rats that consumed fructose or maltodextrin.
      Histone H3 acetylation and MEF2A binding paralleled the accessibility pattern.
      These findings indicate that both fructose and maltodextrin modulate the GLUT4
      adaptive response to exercise by mechanisms involving chromatin remodeling at the
      Glut4 promoter. 

PMID- 24326424
TI  - Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis
      via the GHSR-independent pathway.
AB  - Doxorubicin is an effective chemotherapeutic agent used to treat malignancies,
      but it causes cardiomyopathy. Preliminary evidence suggests that desacyl ghrelin
      might have protective effects on doxorubicin cardiotoxicity. This study examined
      the cellular effects of desacyl ghrelin on myocardial fibrosis and apoptosis in a
      doxorubicin cardiomyopathy experimental model. Adult C57BL/6 mice received an
      intraperitoneal injection of doxorubicin to induce cardiomyopathy, followed by 4
      day treatment of saline (control) or desacyl ghrelin with or without [d-Lys3]
      GHRP-6 (a growth hormone secretagogue receptor or GHSR1a antagonist). Ventricular
      structural and functional parameters were evaluated by transthoracic
      echocardiography. Molecular and cellular measurements were performed in
      ventricular muscle to examine myocardial fibrosis and apoptosis. Cardiac
      dysfunction was induced by doxorubicin, as indicated by significant decreases in
      ventricular fractional shortening and ejection fraction. This doxorubicin-induced
      cardiac dysfunction was prevented by the treatment of desacyl ghrelin no matter
      with or without the presence of [d-Lys3]-GHRP-6. Doxorubicin induced fibrosis
      (accumulated collagen deposition and increased CTGF), activated apoptosis
      (increased TUNEL index, apoptotic DNA fragmentation, and caspase-3 activity and
      decreased Bcl-2/Bax ratio), and suppressed phosphorylation status of prosurvival
      signals (ERK1/2 and Akt) in ventricular muscles. All these molecular and cellular
      alterations induced by doxorubicin were not found in the animals treated with
      desacyl ghrelin. Notably, the changes in the major markers of apoptosis,
      fibrosis, and Akt phosphorylation were found to be similar in the animals
      following the treatment of desacyl ghrelin with and without GHSR antagonist [d
      Lys3]-GHRP-6. These findings demonstrate clearly that desacyl ghrelin protects
      the cardiomyocytes against the doxorubicin-induced cardiomyopathy by preventing
      the activation of cardiac fibrosis and apoptosis, and the effects are probably
      mediated through GHSR-independent mechanism. 

PMID- 24326423
TI  - ROCK1 isoform-specific deletion reveals a role for diet-induced insulin
      resistance.
AB  - Rho kinase (ROCK) isoforms regulate insulin signaling and glucose metabolism
      negatively or positively in cultured cell lines and skeletal muscle. However, the
      in vivo function of the ROCK1 isoform in adipose tissue has not been addressed.
      To determine the specific role of the adipose ROCK1 isoform in the development of
      insulin resistance and obesity, mice lacking ROCK1 in adipose tissue globally or
      selectively were studied. Here, we show that insulin's ability to activate IRS
      1/PI3K/Akt signaling was greatly enhanced in adipose tissue of ROCK1(-/-) mice
      compared with wild-type mice. These effects resulted from the inhibitory effect
      of ROCK1 on insulin receptor action, as evidenced by the fact that IR tyrosine
      phosphorylation was abolished in ROCK1(-/-) MEF cells when ROCK1 was reexpressed.
      Consistently, adipose-specific disruption of ROCK1 increased IR tyrosine
      phosphorylation in adipose tissue and modestly improved sensitivity to insulin in
      obese mice induced by high-fat feeding. This effect is independent of any changes
      in adiposity, number or size of adipocytes, and metabolic parameters, including
      glucose, insulin, leptin, and triglyceride levels, demonstrating a minimal effect
      of adipose ROCK1 on whole body metabolism. Enzymatic activity of ROCK1 in adipose
      tissue remained ~50%, which likely originated from the fraction of stromal
      vascular cells, suggesting involvement of these cells for adipose metabolic
      regulation. Moreover, ROCK isoform activities were increased in adipose tissue of
      diet-induced or genetically obese mice. These data suggest that adipose ROCK1
      isoform plays an inhibtory role for the regulation of insulin sensitivity in diet
      induced obesity in vivo. 

PMID- 24326425
TI  - Connexin 36 mediates blood cell flow in mouse pancreatic islets.
AB  - The insulin-secreting beta-cells are contained within islets of Langerhans, which
      are highly vascularized. Blood cell flow rates through islets are glucose
      dependent, even though there are no changes in blood cell flow within in the
      surrounding exocrine pancreas. This suggests a specific mechanism of glucose
      regulated blood flow in the islet. Pancreatic islets respond to elevated glucose
      with synchronous pulses of electrical activity and insulin secretion across all
      beta-cells in the islet. Connexin 36 (Cx36) gap junctions between islet beta
      cells mediate this synchronization, which is lost in Cx36 knockout mice (Cx36(-/
      )). This leads to glucose intolerance in these mice, despite normal plasma
      insulin levels and insulin sensitivity. Thus, we sought to investigate whether
      the glucose-dependent changes in intraislet blood cell flow are also dependent on
      coordinated pulsatile electrical activity. We visualized and quantified blood
      cell flow using high-speed in vivo fluorescence imaging of labeled red blood
      cells and plasma. With the use of a live animal glucose clamp, blood cell flow
      was measured during either hypoglycemia (~50 mg/dl) or hyperglycemia (~300
      mg/dl). In contrast to the large glucose-dependent islet blood velocity changes
      observed in wild-type mice, only minimal differences are observed in both Cx36(+/
      ) and Cx36(-/-) mice. This observation supports a novel model where intraislet
      blood cell flow is regulated by the coordinated electrical activity in the islet
      beta-cells. Because Cx36 expression and function is reduced in type 2 diabetes,
      the resulting defect in intraislet blood cell flow regulation may also play a
      significant role in diabetic pathology. 

PMID- 24326427
TI  - Reversible cardiomyopathy after radiofrequency ablation of 30-year persistent
      atrial tachycardia.
AB  - Tachycardia-induced cardiomyopathy (TIC) is a reversible form of the left
      ventricular (LV) systolic dysfunction and is believed to be a relatively acute
      process. We report a TIC case with a 30-year history of long-lasting persistent
      atrial tachycardia involving a 44-year-old man previously diagnosed with dilated
      cardiomyopathy and a low LV ejection fraction (LVEF) of 20%. ECG revealed atrial
      tachycardia at 110-120 bpm. He was hospitalised with a worsening heart failure.
      His clinical status was New York Heart Association functional class III, and
      echocardiography revealed LV dilation and an LVEF of 9%. A two-dimensional
      speckle-tracking strain measurement revealed LV mechanical dyssynchrony. He
      underwent radiofrequency ablation for atrial tachycardia. After restoring sinus
      rhythm, his cardiac symptoms improved immediately. The LV mechanical dyssynchrony
      decreased a week after ablation, without changes in the LV dilation or LVEF.
      Thereafter, the LV dilation and systolic function gradually improved, and atrial
      tachycardia and heart failure remained absent. 

PMID- 24326426
TI  - Combining metformin and aerobic exercise training in the treatment of type 2
      diabetes and NAFLD in OLETF rats.
AB  - Here, we sought to compare the efficacy of combining exercise and metformin for
      the treatment of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) in
      hyperphagic, obese, type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF)
      rats. OLETF rats (age: 20 wk, hyperglycemic and hyperinsulinemic; n = 10/group)
      were randomly assigned to sedentary (O-SED), SED plus metformin (O-SED + M; 300
      mg.kg(-1).day(-1)), moderate-intensity exercise training (O-EndEx; 20 m/min, 60
      min/day, 5 days/wk treadmill running), or O-EndEx + M groups for 12 wk. Long
      Evans Tokushima Otsuka (L-SED) rats served as nonhyperphagic controls. O-SED + M,
      O-EndEx, and O-EndEx + M were effective in the management of type 2 diabetes, and
      all three treatments lowered hepatic steatosis and serum markers of liver injury;
      however, O-EndEx lowered liver triglyceride content and fasting hyperglycemia
      more than O-SED + M. In addition, exercise elicited greater improvements compared
      with metformin alone on postchallenge glycemic control, liver diacylglycerol
      content, hepatic mitochondrial palmitate oxidation, citrate synthase, and beta
      HAD activities and in the attenuation of markers of hepatic fatty acid uptake and
      de novo fatty acid synthesis. Surprisingly, combining metformin and aerobic
      exercise training offered little added benefit to these outcomes, and in fact,
      metformin actually blunted exercise-induced increases in complete mitochondrial
      palmitate oxidation and beta-HAD activity. In conclusion, aerobic exercise
      training was more effective than metformin administration in the management of
      type 2 diabetes and NAFLD outcomes in obese hyperphagic OLETF rats. Combining
      therapies offered little additional benefit beyond exercise alone, and findings
      suggest that metformin potentially impairs exercise-induced hepatic mitochondrial
      adaptations. 

PMID- 24326428
TI  - All contraindications to thrombolysis for life-threatening pulmonary embolus
      should be considered relative.
AB  - Acute massive pulmonary embolism (PE) can be fatal; however, timely thrombolytic
      therapy can be life saving. Guidelines advocate the use of thrombolysis for
      massive PE in patients with an acceptable bleeding-risk profile. Nonetheless,
      estimating what constitutes an acceptable bleeding risk in those with life
      threatening PE is a clinical challenge, and even contraindications considered
      'absolute' may present lesser risk than leaving PE untreated. We discuss the case
      of a 77-year-old man who received thrombolysis for a massive PE 4 weeks following
      admission with a significant intracerebral bleed. There was rapid resolution of
      hypotension and hypoxia and he survived to be discharged home. This case is used
      to illustrate that no potential therapy should be discounted in patients faced
      with acute life-threatening PE. Decisions to thrombolyse patients with
      traditional contraindications-even those considered absolute-must be taken by
      clinicians able to weigh relative risks. 

PMID- 24326429
TI  - Unusual head metastasis of kidney cancer.
AB  - Renal cell carcinoma (RCC) metastasis can involve any organ. Head metastasis are
      rare, namely tongue, scalp and nose and only a few cases have been described. The
      authors describe three cases of unusual presentation of head metastasis of RCC.
      In case 1, a 50-year-old man with RCC underwent left nephrectomy, and presented
      16 months later with nasal metastasis. In case 2, a 64-year-old woman with RCC
      operated 12 years ago, relapsed at multiple sites including scalp, which was
      treated surgically. In case 3, a 47-year-old man with RCC developed metastasis in
      multiple organs including a mass on the tongue that was operated and was
      compatible with primary tumour metastasis. These cases show the importance of
      correct diagnosis of rare presentations and local treatment of metastasis of RCC.

PMID- 24326430
TI  - Pseudomelanosis duodeni in a postrenal transplant patient.
AB  - Pseudomelanosis duodeni is a rare entity characterised by dark pigmented
      intracellular granules seen within macrophages that lie within the lamina propria
      of the duodenal villi. There is no known treatment, and the clinical significance
      and long-term sequelae of this entity are unclear. We present a case of
      pseudomelanosis duodeni in a 54-year-old woman who presented with a 1-month
      history of nausea, vomiting and non-bloody diarrhoea. The medical history was
      significant for diabetes mellitus type 2, end-stage renal disease status
      postkidney transplant, hypertension, anaemia of chronic disease and
      hypothyroidism. A gastroduodenal endoscopy revealed pigmented dark lesions in the
      duodenal mucosa. Biopsies from the second part of the duodenum and duodenal bulb
      showed pigmented macrophages in the lamina propria. The findings were consistent
      with duodenal melanosis. In spite of renal transplant with normalisation of renal
      function, the duodenal melanosis persists, which raises questions on the role of
      renal impairment in this entity. 

PMID- 24326431
TI  - Nematode infection mimicking paratesticular malignancy.
AB  - Paratesticular swellings pose a diagnostic dilemma due to concerns over
      malignancy. We present a case of paratesticular swelling in a 13-year-old boy as
      a result of Dirofilaria immitis infection. The boy presented with a 2-month
      history of right testicular discomfort associated with an irregular mass within
      the scrotum. 

PMID- 24326432
TI  - Choroidal melanoma presenting with anterior segment involvement and phthisis
      bulbi.

PMID- 24326433
TI  - Early second trimester uterine scar rupture.
AB  - Spontaneous uterine scar rupture can be lethal in pregnant women. A spontaneous
      uterine scar rupture in the early mid-trimester is rare and difficult to
      diagnose. This is a case of a 30-year-old woman (G2P1L1) at 19 weeks of gestation
      and having undergone a previous caesarean section presented with acute abdomen in
      shock. Laparotomy revealed a uterine scar rupture, which was resutured after
      evacuation of products of conception. This case merits that the uterine rupture
      should be considered as a differential diagnosis in pregnant women presenting
      with acute abdomen. In this case, although there was uterine rupture in the
      second trimester and a complete placental separation, fetus was alive which is
      quite unusual in patients presenting with rupture uterus. 

PMID- 24326434
TI  - Stridor in an 11-year-old child.
AB  - Stridor in older children can be due to diverse aetiology that includes
      infections, anaphylaxis and rarely systemic conditions leading to hypocalcaemia.
      We report the case of a previously asymptomatic 11-year-old girl who presented to
      the casualty with stridor due to hypocalcaemia. The aetiological investigations
      for hypocalcaemia uncovered previously undetected chronic renal failure, possibly
      due to a rare autosomal recessive condition called nephronophthisis. We report
      this case to highlight the importance of widening the diagnostic focus for
      children presenting with stridor, especially when they fall outside the usual age
      group for infections like croup, or when the history is atypical. 

PMID- 24326435
TI  - Small bowel injury after suprapubic catheter insertion presenting 3 years after
      initial insertion.
AB  - A 77-year-old woman was referred to urology with blockages of her suprapubic
      catheter (SPC). The catheter was replaced easily in the emergency department,
      however, no urine was draining, only a cloudy green fluid was visible. On
      cystoscopy bilious material was identified in the bladder. There was no catheter
      visible. There seemed to be a fistulous tract entering the bladder at the left
      dome. The urethra was dilated, a urethral catheter was placed and the SPC was
      removed. A CT demonstrated that the SPC tract transfixed a loop of pelvic small
      bowel and entered the bladder with no intraperitoneal contrast leak. The patient
      recovered well and did not require laparotomy. This case emphasises that bowel
      perforation, although rare, must be considered as a complication of SPC placement
      even years after initial insertion when catheter problems arise. Unusually, we
      learn that this complication may not present with abdominal pain or peritonism. 

PMID- 24326436
TI  - Myositis ossificans: the mimicker.
AB  - A 14-year-old boy presented with upper backache and a painful swelling in the
      right paraspinal region for 7 days. He had no history of trauma. MRI showed a non
      specific ill-defined heterogeneous lesion, which showed intense postcontrast
      enhancement. Ultrasonogram showed a peripheral sheet of calcification around the
      lesion. A CT scan showed a faint rim of calcification, which increased in
      thickness over weeks, confirming the diagnosis as myositis ossificans. We present
      our approach to the case and also review the imaging features of different stages
      of the disease process and their differentials. 

PMID- 24326437
TI  - Poststroke psychosis in an 8-year-old child with moyamoya disease.
AB  - Psychiatric illnesses following cerebrovascular accidents has been a popular area
      of research in recent times. Though poststroke anxiety and mood disorders
      including depression have been reported often, reports of poststroke psychosis
      have been considerably rarer. This case report documents an even rarer occurrence
      of a psychotic disorder in an 8-year-old child with moyamoya disease following a
      cerebrovascular accident. The child was managed with low-dose atypical
      antipsychotic, risperidone and the psychotic symptoms eventually were under
      control around 3 weeks following the initiation of psychotropic medication. 

PMID- 24326438
TI  - Rare occurrence of a transient isolated unilateral partial third nerve palsy
      after angioplasty.

PMID- 24326439
TI  - Necrotising fasciitis.
AB  - A patient in his late 50s who suffered from necrotising fasciitis is described in
      this case report. The patient first presented at the chest pain unit, where he
      reported of respiratory distress and showed systemic signs of an infection.
      Because of progressive skin lesions indicative of necrotising fasciitis on both
      the lower extremities, the patient was immediately rushed into surgery and was
      treated at the intensive care unit. Despite receiving immediate treatment, the
      patient died of this rapidly spreading infectious disease. Because of the fast
      advance of this disease, we would like to emphasise the importance of early
      recognition of symptoms. 

PMID- 24326440
TI  - Late diagnosis of Lesch-Nyhan disease variant.
AB  - A 30-year-old man was referred for investigation and management of
      hyperuricaemia. History included recurrent nephrolithiasis and chronic gout with
      poor response to medical management. Hypoxanthine-guanine
      phosphoribosyltransferase (HGPRT) enzyme activity was investigated and found to
      be deficient confirming the diagnosis of Lesch-Nyhan disease. Hyperuricaemia was
      treated with allopurinol. To prevent nephrolithiasis, the patient was instructed
      to avoid dehydration and aim for a minimum urine output of 2 L/day. Urinary
      alkalinisation with potassium citrate was started. The patient was referred for
      genetic counselling. This case discusses the genetics, pathophysiology, clinical
      manifestations, diagnosis and management of HGPRT deficiency. 

PMID- 24326441
TI  - Empyema necessitans: very late complication of pulmonary tuberculosis.
AB  - Empyema necessitans is a rare clinical finding nowadays. We report the case of a
      patient admitted in our ward for investigation of an unknown onset anterior chest
      wall mass, with no accompanying signs or symptoms. It is noteworthy that the
      patient had had pulmonary tuberculosis submitted to thoracoplasty more than 60
      years before. Thoracic MRI showed a large heterogeneous mass, with a thick wall
      and internal septations located at the right anterior chest wall, as well as a
      heterogeneous content inside the right pleural cavity, with direct communication
      between both. An aspirative puncture of both masses was performed, with positive
      cultures for Mycobacterium tuberculosis, thus leading to the diagnosis of pleural
      tuberculosis with anterior chest wall empyema necessitans. A drain was inserted
      and antibiotics started. This case draws our attention to a very rare
      complication of pulmonary tuberculosis and its surgical treatment, though it
      aroused many decades after primary infection. 

PMID- 24326442
TI  - Primary synovial chondromatosis of the ankle joint presenting as monoarthritis.

PMID- 24326443
TI  - Claudication without risk factors: a case of popliteal entrapment syndrome.

PMID- 24326444
TI  - Acquired left coronary artery fistulae to pulmonary artery and superior vena
      cava.

PMID- 24326445
TI  - Erosive polyarticular tophaceous gout: an unusually deforming and destructive
      presentation.

PMID- 24326446
TI  - ESR of coupled spin-1/2 chains in copper pyrazine dinitrate: unveiling
      geometrical frustration.
AB  - The spin dynamics of copper pyrazine dinitrate (Cu(C4H4N2)(NO3)2), a model spin
      1/2 Heisenberg antiferromagnetic (AF) chain system, was investigated by means of
      electron spin resonance (ESR). Using the high-field ESR we evidenced the
      inequivalence of Cu sites belonging to adjacent spin chains in the ac planes of
      this compound. It was revealed that the dominating interchain interaction is of
      zig-zag-type. This interaction gives rise to geometrical frustration strongly
      affecting the character of AF ordering. Combining our experimental findings with
      the results of a quasiclassical approach we predict that at low temperatures the
      system orders in an incommensurate spiral state. 

PMID- 24326447
TI  - Diagnosing intracranial aneurysms with MR angiography: systematic review and meta
      analysis.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate the sensitivity and
      specificity of MR angiography (MRA) in the diagnosis of ruptured and unruptured
      intracranial aneurysms. METHODS: A systematic search was performed on 4
      electronic databases on relevant articles that were published from January 1998
      to October 2013. Inclusion criteria were met by 12 studies that compared MRA with
      digital subtraction angiography as reference standard. Two independent reviewers
      evaluated the methodological quality of the studies. Data from eligible studies
      were extracted and used to construct 2*2 contingency tables on a per-aneurysm
      level. Pooled estimates of sensitivity and specificity were calculated for all
      studies and subgroups of studies. Heterogeneity was tested, and risk for
      publication bias was assessed. RESULTS: Included studies were of high
      methodological quality. Studies with larger sample size tended to have higher
      diagnostic performance. Most studies used time-of-flight MRA technique. Among the
      960 patients assessed, 772 aneurysms were present. Heterogeneity with reference
      to sensitivity and specificity was moderate to high. Pooled sensitivity of MRA
      was 95% (95% confidence interval, 89%-98%), and pooled specificity was 89% (95%
      confidence interval, 80%-95%). False-negative and false-positive aneurysms
      detected on MRA were mainly located at the skull base and middle cerebral artery.
      Freehand 3-dimensional reconstructions performed by the radiologist significantly
      increased diagnostic performance. Studies performed on 3 Tesla showed a trend
      toward higher performance (P=0.054). CONCLUSIONS: Studies on diagnostic
      performance of MRA show high sensitivity with large variation in specificity in
      the detection of intracranial aneurysms.

PMID- 24326448
TI  - Coffee, tea, and cocoa and risk of stroke.
AB  - Current evidence from experimental studies in animals and humans along with
      findings from prospective studies indicates beneficial effects of green and black
      tea as well as chocolate on cardiovascular health, and that tea and chocolate
      consumption may reduce the risk of stroke. The strongest evidence exists for
      beneficial effects of tea and cocoa on endothelial function, total and LDL
      cholesterol (tea only), and insulin sensitivity (cocoa only). The majority of
      prospective studies have reported a weak inverse association between moderate
      consumption of coffee and risk of stroke. However, there are yet no clear
      biological mechanisms whereby coffee might provide cardiovascular health
      benefits. Awaiting the results from further long-term RCTs and prospective
      studies, moderate consumption of filtered coffee, tea, and dark chocolate seems
      prudent.

PMID- 24326449
TI  - Letter by Taguchi et al regarding article, "Granulocyte colony-stimulating factor
      in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke
      Trial".

PMID- 24326450
TI  - Response to letter regarding article, "Granulocyte colony-stimulating factor in
      patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke
      Trial".

PMID- 24326451
TI  - Characteristics and outcomes of patients with multiple cervical artery
      dissection.
AB  - BACKGROUND AND PURPOSE: Little is known about factors contributing to multiple
      rather than single cervical artery dissections (CeAD) and their associated
      prognosis. METHODS: We compared the baseline characteristics and short-term
      outcome of patients with multiple to single CeAD included in the multicenter
      Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study. RESULTS:
      Among the 983 patients with CeAD, 149 (15.2%) presented with multiple CeAD.
      Multiple CeADs were more often associated with cervical pain at admission (odds
      ratio [OR], 1.59; 95% confidence interval [CI], 1.10-2.30), a remote history of
      head or neck surgery (OR, 1.87; 95% CI, 1.16-3.00), a recent infection (OR, 1.71;
      95% CI, 1.12-2.61), and cervical manipulation (OR, 2.23; 95% CI, 1.26-3.95). On
      imaging, cervical fibromuscular dysplasia (OR, 3.97; 95% CI, 2.04-7.74) and the
      presence of a pseudoaneurysm (OR, 2.91; 95% CI, 1.86-4.57) were more often seen
      in patients with multiple CeAD. The presence of multiple rather than single CeAD
      had no effect on functional 3-month outcome (modified Rankin Scale score, >=3;
      12% in multiple CeAD versus 11.9% in single CeAD; OR, 1.20; 95% CI, 0.60-2.41).
      CONCLUSIONS: In the largest published series of patients with CeAD, we
      highlighted significant differences between multiple and single artery
      involvement. Features suggestive of an underlying vasculopathy (fibromuscular
      dysplasia) and environmental triggers (recent infection, cervical manipulation,
      and a remote history of head or neck surgery) were preferentially associated with
      multiple CeAD.

PMID- 24326453
TI  - Ganglioside GM3 depletion reverses impaired wound healing in diabetic mice by
      activating IGF-1 and insulin receptors.
AB  - Ganglioside GM3 mediates adipocyte insulin resistance, but the role of GM3 in
      diabetic wound healing, a major cause of morbidity, is unclear. The purpose of
      this study was to determine whether GM3 depletion promotes diabetic wound healing
      and directly activates keratinocyte (KC) insulin pathway signaling. GM3 synthase
      (GM3S) expression is increased in human diabetic foot skin, ob/ob and diet
      induced obese diabetic mouse skin, and in mouse KCs exposed to increased glucose.
      GM3S knockout in diet-induced obese mice prevents the diabetic wound-healing
      defect. KC proliferation, migration, and activation of insulin receptor (IR) and
      insulin growth factor-1 receptor (IGF-1R) are suppressed by excess glucose in
      wild-type cells, but increased in GM3S (-/-) KCs with supplemental glucose. Co
      immunoprecipitation of IR, IR substrate 1 (IRS-1), and IGF-1R, and increased IRS
      1 and Akt phosphorylation accompany receptor activation. GM3 supplementation or
      inhibition of IGF-1R or PI3K reverses the increased migration of GM3S(-/-) KCs,
      whereas IR knockdown only partially suppresses migration. 

PMID- 24326455
TI  - Time to breast cancer relapse predicted by primary tumour characteristics, not
      lymph node involvement.
AB  - INTRODUCTION: The risk of breast cancer recurrence has been linked to tumour
      size, grade, oestrogen (ER) receptor status, and degree of lymph node (LN)
      involvement. However, the role of these variables in predicting time to relapse
      is not well defined. This study was designed to identify patient and primary
      tumour characteristics that predict risk periods for breast cancer recurrence
      within our institution, to enable more tailored surveillance strategies. METHODS:
      We retrospectively studied a cohort of 473 patients who presented to The Queen
      Elizabeth Hospital, Adelaide, Australia, with recurrent breast cancer between
      1968 and 2008. Patient and primary tumour characteristics were collected,
      including age, menopausal status, tumour grade, size, ER and progesterone
      receptor (PR) status, and LN involvement and modeled against time to relapse
      using Kaplan-Meier survival curves. RESULTS: High tumour grade, size >= 20 mm, ER
      negativity, and PR negativity were shown on univariate analysis to correlate
      significantly with earlier recurrence (P < 0.0001, P = 0.0012, P = 0.0006, and P
      = 0.006). Multivariate analysis identified tumour grade and size as significant
      predictors of timing of relapse after adjustment for other variables. LN
      involvement, menopausal status, and age did not significantly correlate with
      earlier recurrence. CONCLUSIONS: High tumour grade and larger size were shown to
      independently predict earlier breast cancer relapse. While LN involvement
      increases absolute recurrence risk, our study proposes that it does not influence
      timing of relapse. Use of these predictors will enable key risk periods for onset
      of relapse to be characterised according to tumour profile with more appropriate
      discharge to primary care providers for ongoing surveillance.

PMID- 24326454
TI  - Toll-like receptor-4 deficiency enhances repair of UVR-induced cutaneous DNA
      damage by nucleotide excision repair mechanism.
AB  - UVB-induced DNA damage has a critical role in the development of
      photoimmunosuppression. The purpose of this study was to determine whether repair
      of UVB-induced DNA damage is regulated by Toll-like receptor-4 (TLR4). When TLR4
      gene knockout (TLR4(-/-)) and TLR4-competent (TLR4(+/+)) mice were subjected to
      90 mJ cm(-2) UVB radiation locally, DNA damage in the form of cyclobutane
      pyrimidine dimers (CPDs) was repaired more efficiently in the skin and bone
      marrow-derived dendritic cells (BMDCs) of TLR4(-/-) mice in comparison to
      TLR4(+/+) mice. Expression of DNA repair gene XPA (xeroderma pigmentosum
      complementation group A) was significantly lower in skin and BMDCs of TLR4(+/+)
      mice than TLR4(-/-) mice after UVB exposure. When cytokine levels were compared
      in these strains after UVB exposure, BMDCs from UV-irradiated TLR4(-/-) mice
      produced significantly more interleukin (IL)-12 and IL-23 cytokines (P<0.05) than
      BMDCs from TLR4(+/+) mice. Addition of anti-IL-12 and anti-IL-23 antibodies to
      BMDCs of TLR4(-/-) mice (before UVB exposure) inhibited repair of CPDs, with a
      concomitant decrease in XPA expression. Addition of TLR4 agonist to TLR4(+/+)
      BMDC cultures decreased XPA expression and inhibited CPD repair. Thus, strategies
      to inhibit TLR4 may allow for immunopreventive and immunotherapeutic approaches
      for managing UVB-induced cutaneous DNA damage and skin cancer. 

PMID- 24326456
TI  - ALPPS for patients with colorectal liver metastases: effective liver hypertrophy,
      but early tumor recurrence.
AB  - BACKGROUND: Associating liver partition and portal vein ligation for staged
      hepatectomy (ALPPS) is a promising method to increase resectability rates of
      liver tumors. Little has been published about oncological results so far. This
      report describes clinical evidence regarding a possible effect of ALPPS on tumor
      recurrence. METHODS: Ten ALPPS procedures were performed for otherwise non
      resectable colorectal liver metastases. Seven of these ten patients had a follow
      up of at least 3 months and were analyzed for tumor recurrence. RESULTS: Six of
      these seven patients had tumor recurrence to the liver. Three of seven patients
      presented with lung metastases, occurring earlier than liver metastases in two of
      three cases. One patient with a follow-up of 3 months had no visible recurrent
      disease, but increasing carcinoembryonic antigen levels. CONCLUSIONS: The patient
      group operable only through ALPPS is at high risk for recurrence and early tumor
      progression. Still, this new method is the only chance for an oncological
      treatment strategy including a surgical approach and possibly better outcome.

PMID- 24326457
TI  - Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance
      and enabling drug-gene co-delivery to cancer cells.
AB  - Having unique architectural features, cationic polymeric nanocapsules (NCs) with
      well-defined covalently stabilized biodegradable structures were generated as
      potentially universal and safe therapeutic nanocarriers. These NCs were
      synthesized from allyl-functionalized cationic polylactide (CPLA) by highly
      efficient UV-induced thiol-ene interfacial cross-linking in transparent
      miniemulsions. With tunable nanoscopic sizes, negligible cytotoxicity and
      remarkable degradability, they are able to encapsulate doxorubicin (Dox) with
      inner cavities and bind interleukin-8 (IL-8) small interfering RNA (siRNA) with
      cationic shells. The Dox-encapsulated NCs can effectively bypass the P
      glycoprotein (Pgp)-mediated multidrug resistance of MCF7/ADR cancer cells,
      thereby resulting in increased intracellular drug concentration and reduced cell
      viability. In vitro studies also showed that the NCs loaded with Dox, IL-8 siRNA
      and both agents can be readily taken up by PC3 prostate cancer cells, resulting
      in a significant chemotherapeutic effect and/or IL-8 gene silencing. 

PMID- 24326458
TI  - Genetic dissection of drought tolerance in chickpea (Cicer arietinum L.).
AB  - KEY MESSAGE: Analysis of phenotypic data for 20 drought tolerance traits in 1-7
      seasons at 1-5 locations together with genetic mapping data for two mapping
      populations provided 9 QTL clusters of which one present on CaLG04 has a high
      potential to enhance drought tolerance in chickpea improvement. Chickpea (Cicer
      arietinum L.) is the second most important grain legume cultivated by resource
      poor farmers in the arid and semi-arid regions of the world. Drought is one of
      the major constraints leading up to 50% production losses in chickpea. In order
      to dissect the complex nature of drought tolerance and to use genomics tools for
      enhancing yield of chickpea under drought conditions, two mapping populations
      ICCRIL03 (ICC 4958 * ICC 1882) and ICCRIL04 (ICC 283 * ICC 8261) segregating for
      drought tolerance-related root traits were phenotyped for a total of 20 drought
      component traits in 1-7 seasons at 1-5 locations in India. Individual genetic
      maps comprising 241 loci and 168 loci for ICCRIL03 and ICCRIL04, respectively,
      and a consensus genetic map comprising 352 loci were constructed (
      http://cmap.icrisat.ac.in/cmap/sm/cp/varshney/). Analysis of extensive genotypic
      and precise phenotypic data revealed 45 robust main-effect QTLs (M-QTLs)
      explaining up to 58.20% phenotypic variation and 973 epistatic QTLs (E-QTLs)
      explaining up to 92.19% phenotypic variation for several target traits. Nine QTL
      clusters containing QTLs for several drought tolerance traits have been
      identified that can be targeted for molecular breeding. Among these clusters, one
      cluster harboring 48% robust M-QTLs for 12 traits and explaining about 58.20%
      phenotypic variation present on CaLG04 has been referred as "QTL-hotspot". This
      genomic region contains seven SSR markers (ICCM0249, NCPGR127, TAA170, NCPGR21,
      TR11, GA24 and STMS11). Introgression of this region into elite cultivars is
      expected to enhance drought tolerance in chickpea.

PMID- 24326459
TI  - Construction of an integrative linkage map and QTL mapping of grain yield-related
      traits using three related wheat RIL populations.
AB  - A novel high-density consensus wheat genetic map was obtained based on three
      related RIL populations, and the important chromosomal regions affecting yield
      and related traits were specified. A prerequisite for mapping quantitative trait
      locus (QTL) is to build a genetic linkage map. In this study, three recombinant
      inbred line populations (represented by WL, WY, and WJ) sharing one common
      parental line were used for map construction and subsequently for QTL detection
      of yield-related traits. PCR-based and diversity arrays technology markers were
      screened in the three populations. The integrated genetic map contains 1,127
      marker loci, which span 2,976.75 cM for the whole genome, 985.93 cM for the A
      genome, 922.16 cM for the B genome, and 1,068.65 cM for the D genome. Phenotypic
      values were evaluated in four environments for populations WY and WJ, but three
      environments for population WL. Individual and combined phenotypic values across
      environments were used for QTL detection. A total of 165 putative additive QTL
      were identified, 22 of which showed significant additive-by-environment
      interaction effects. A total of 65 QTL (51.5%) were stable across environments,
      and 23 of these (35.4%) were common stable QTL that were identified in at least
      two populations. Notably, QTkw-5B.1, QTkw-6A.2, and QTkw-7B.1 were common major
      stable QTL in at least two populations, exhibiting 11.28-16.06, 5.64-18.69, and
      6.76-21.16% of the phenotypic variance, respectively. Genetic relationships
      between kernel dimensions and kernel weight and between yield components and
      yield were evaluated. Moreover, QTL or regions that commonly interact across
      genetic backgrounds were discussed by comparing the results of the present study
      with those of previous similar studies. The present study provides useful
      information for marker-assisted selection in breeding wheat varieties with high
      yield.

PMID- 24326460
TI  - Amnion-derived mesenchymal stromal cells show a mesenchymal-epithelial phenotype
      in culture.
AB  - The amnionic membrane is a rich source of multipotent mesenchymal stromal cells
      (hAMSC), which are readily available and show a potential use in regenerative
      medicine and tissue engineering. Before these cells can be applied clinically,
      careful characterization is necessary, especially as primary cells are known to
      change their phenotype in culture. We analyzed the mesenchymal phenotype of hAMSC
      at different stages after isolation using immunohistochemistry. Shortly after
      isolation (1 day), 92 % (+/- 7 %) of the hAMSC expressed the mesenchymal marker
      vimentin, 2 % (+/- 1 %) stained for the epithelial marker cytokeratin-7 and 5 %
      (+/- 4 %) co-expressed these markers. After 5 days, the double positive cells
      slightly increased to 7 % (+/- 3 %), while exclusive expression of cytokeratin-7
      or vimentin remained unchanged (1 % +/- 2 % and 92 % +/- 1 %, respectively).
      After the first passage, all attached cells were vimentin-positive, while 54 %
      (+/- 9 %) co-expressed cytokeratin-7 and vimentin. Thus, we conclude that under
      culture, hAMSC adopt a hybrid mesenchymal-epithelial phenotype. It is also
      essential to perform microscopical examination during the first days after
      isolation to detect contaminations with human amnion-derived epithelial cells in
      cultures of hAMSC.

PMID- 24326463
TI  - Practicing pathology in the era of big data and personalized medicine.
AB  - The traditional task of the pathologist is to assist physicians in making the
      correct diagnosis of diseases at the earliest possible stage to effectuate the
      optimal treatment strategy for each individual patient. In this respect surgical
      pathology (the traditional tissue diagnosis) is but a tool. It is not, of itself,
      the purpose of pathology practice; and change is in the air. This January 2014
      issue of Applied Immunohistochemistry and Molecular Morphology (AIMM) embraces
      that change by the incorporation of the agenda and content of the journal
      Diagnostic Molecular Morphology (DMP). Over a decade ago AIMM introduced and
      promoted the concept of "molecular morphology," and has sought to publish
      molecular studies that correlate with the morphologic features that continue to
      define cancer and many diseases. That intent is now reinforced and extended by
      the merger with DMP, as a logical and timely response to the growing impact of a
      wide range of genetic and molecular technologies that are beginning to reshape
      the way in which pathology is practiced. The use of molecular and genomic
      techniques already demonstrates clear value in the diagnosis of disease, with
      treatment tailored specifically to individual patients. Personalized medicine is
      the future, and personalized medicine demands personalized pathology. The need
      for integration of the flood of new molecular data, with surgical pathology,
      digital pathology, and the full range of pathology data in the electronic medical
      record has never been greater. This review describes the possible impact of these
      pressures upon the discipline of pathology, and examines possible outcomes. There
      is a sense of excitement and adventure. Active adaption and innovation are
      required. The new AIMM, incorporating DMP, seeks to position itself for a central
      role in this process.

PMID- 24326464
TI  - In vitro reproduction of the life cycle of Pythium insidiosum from kunkers'
      equine and their role in the epidemiology of pythiosis.
AB  - Pythium insidiosum is an important pathogen of mammals' species, including
      humans. Equine is the main species affected by this oomycete. P. insidiosum
      requires an aquatic environment to develop its life cycle, and the susceptible
      hosts are contaminated when they contact the microorganism in swampy areas. The
      equine pythiosis is characterized by the formation of irregular masses within the
      cutaneous lesions, called kunkers, which easily detach from the lesion. From
      these structures, it is possible to isolate P. insidiosum in pure cultures. The
      present study aimed to reproduce in vitro the life cycle of P. insidiosum from
      kunkers of equine clinical lesions. Fifteen kunkers from different horses were
      tested. It was observed that the discharge of zoospores occurred after 24-48 h of
      incubation at 37  degrees C in, respectively, 40 and 47 % of the kunkers
      evaluated. Only two samples showed no development of the asexual cycle of P.
      insidiosum under the conditions tested. It was possible to demonstrate that
      kunkers are able to restart the asexual cycle of P. insidiosum. Based on our in
      vitro results, we highlight the importance of these structures in the
      epidemiology of the pythiosis, since kunkers can be a potential source of
      contamination of this oomycete for aquatic environments.

PMID- 24326465
TI  - Off to a flying start.

PMID- 24326466
TI  - Non-acute myocardial infarction-related causes of elevated high-sensitive
      troponin T in the emergency room: a cross-sectional analysis.
AB  - To systematically investigate putative causes of non-coronary high-sensitive
      troponin elevations in patients presenting to a tertiary care emergency
      department. In this cross-sectional analysis, patients who received serial
      measurements of high-sensitive troponin T between 1 August 2010 and 31 October
      2012 at the Department of Emergency Medicine were included. The following
      putative causes were considered to be associated with non-acute coronary syndrome
      related increases in high-sensitive troponin T: acute pulmonary embolism, renal
      insufficiency, aortic dissection, heart failure, peri-/myocarditis, strenuous
      exercise, rhabdomyolysis, cardiotoxic chemotherapy, high-frequency ablation
      therapy, defibrillator shocks, cardiac infiltrative disorders (e.g.,
      amyloidosis), chest trauma, sepsis, shock, exacerbation of chronic obstructive
      pulmonary disease, and diabetic ketoacidosis. During the study period a total of
      1,573 patients received serial measurements of high-sensitive troponin T. Of
      these, 175 patients were found to have acute coronary syndrome leaving 1,398
      patients for inclusion in the study. In 222 (30 %) of patients, no putative cause
      described in the literature could be attributed to the elevation in high
      sensitive troponin T observed. The most commonly encountered mechanism underlying
      the troponin T elevation was renal insufficiency that was present in 286 patients
      (57 %), followed by cerebral ischemia in 95 patients (19 %), trauma in 75
      patients (15 %) and heart failure in 41 patients (8 %). Non-acute coronary
      syndrome-associated elevation of high-sensitive troponin T levels is commonly
      observed in the emergency department. Renal insufficiency and acute cerebral
      events are the most common conditions associated with high-sensitive troponin T
      elevation. 

PMID- 24326468
TI  - A new year and some new ideas-including motivational interviewing!

PMID- 24326469
TI  - Roughly 14% of Infants Share Bed With Adult or Child.

PMID- 24326467
TI  - Efficacy of artemether and artesunate in mice infected with praziquantel non
      susceptible isolate of Schistosoma japonicum.
AB  - Praziquantel is currently the only drug of choice for the treatment of human
      Schistosoma japonicum infections, and praziquantel-based chemotherapy has been
      proved to be generally effective to control the morbidity and reduce the
      prevalence and intensity of S. japonicum infections. However, the potential
      emergence of praziquantel resistance in S. japonicum seriously threatens the
      elimination of this neglected tropical disease in China. The purpose of this
      study was designed, in mouse animals, to evaluate the in vivo efficacy of
      artemether and artesunate against praziquantel non-susceptible S. japonicum. Mice
      infected with a praziquantel non-susceptible isolate and a praziquantel
      susceptible isolate of S. japonicum were treated with artemether and artesunate
      at a single oral dose of 300 mg/kg given once on each of days 7-8 and 35-36 post
      infection to assess the efficacy against juvenile and adult worms. Administration
      with artemether and artesunate at a single oral dose of 300 mg/kg on each of days
      7-8 post-infection resulted in total worm burden reductions of 72.8 and 73.5% in
      mice infected with praziquantel-susceptible S. japonicum, and 77.9 and 74.1% in
      mice infected with the non-susceptible isolate (both P values >0.05), while the
      same treatments given on days 35-36 post-infection reduced total worm burdens by
      71.4 and 69.6% in mice infected with the susceptible isolate, and 75.3 and 69.6%
      in mice infected with the non-susceptible parasite (both P values >0.05). It is
      concluded that there is no evidence for reduced susceptibility of artemether and
      artesunate in praziquantel non-susceptible S. japonicum.

PMID- 24326470
TI  - Validating a multifactorial falls risk assessment.
AB  - Reducing risk of falls has been identified as a national safety goal by The Joint
      Commission (TJC). The purpose was to determine if the total score on the
      multifactorial Falls Risk Assessment accurately identifies the risk of falls in a
      homebound client. In addition, the study examined if any individual item had a
      higher predictive power with the incidence of falls. One hundred clients (> 65
      years old) who sustained an avoidable fall during a home care episode of care,
      plus 25 home care clients in the same age range and time period, who did not
      fall. A retrospective chart review, including Falls Risk Assessment (FRA)
      performed at start of care, demographic information, specific physical therapy
      (PT) evaluation, and visit notes if necessary to determine if the fall met the
      inclusion criteria. Scores for each individual area of the assessment were
      collected for statistical analysis. Data were analyzed by a biostatistician using
      simple linear regression, t-tests, and regression of variable combinations. The
      total score on the multifactorial risk assessment tool was shown to have a strong
      relationship with incidence of falls. The average scores of individuals who fell
      after assessment were significantly higher than those of individuals who did not
      fall. No single factors were found to be highly predictive. A single approach to
      decreasing falls is likely to be less effective than a multipronged approach.
      Caregivers and providers are advised to consider the entirety of the falls risk
      and direct comprehensive interventions to address the multiple factors that lead
      to falls. 

PMID- 24326471
TI  - Enhancing cultural competency in home care nurses caring for hispanic/latino
      patients.
AB  - The Latino population is the fastest growing ethnically diverse group in the
      United States, but U.S. healthcare studies report poorer health status in this
      population than in non-Latinos. Using Campinha-Bacote's Inventory for Assessing
      the Process of Cultural Competence Among Healthcare Professionals-Revised (IAPCC
      R, 2003), a single-session pilot educational program to enhance culturally
      responsive home care nursing to Latinos resulted in a 27% increase in the nurse
      participant cultural competency levels. 

PMID- 24326472
TI  - Effectiveness of wound, ostomy and continence-certified nurses on individual
      patient outcomes in home health care.
AB  - PURPOSE: To assess whether there was a significant improvement and stabilization
      (not worse at discharge) in pressure ulcers, lower extremity venous ulcers,
      surgical wounds, urinary incontinence, bowel incontinence, and urinary tract
      infections in home health care (HHC) patients cared for by a certified WOC nurse.
      SUBJECTS AND SETTING: There were 449,170 episodes of care from a national
      convenience sample of 785 HHC agencies with 447,309 nonmaternity, adult patients
      between October 1, 2008, and December 31, 2009. DESIGN: Descriptive and
      comparative. INSTRUMENTS AND METHODS: Data from the Outcome and Assessment
      Information Set documented by HHC clinicians were analyzed using mixed-effects
      logistic regression, propensity score analysis, and appropriate parametric and
      nonparametric tests. An Internet survey identified whether WOC nurses provided
      care to patients in an HHC agency. Home health care agencies identified records
      of patients receiving WOC nurse visits/consults. RESULTS: An HHC patient assigned
      to a WOC nurse had surgical wounds, pressure ulcers, and incontinence problems
      that were significantly worse than HHC patients not assigned to a WOC nurse.
      Patients cared for by a WOC nurse showed significant improvement and
      stabilization of the number of pressure ulcers and surgical wounds and the
      frequency of urinary and bowel incontinence, despite having problems that were
      more severe than other patients. Home health care patients not cared for by WOC
      nurses, with less-severe wound and incontinence problems, also got better.
      CONCLUSIONS: WOC nurses are effective in achieving positive health outcomes for
      pressure ulcers, surgical wounds, and incontinence in HHC patients with severe
      health problems.

PMID- 24326473
TI  - Bag technique: preventing and controlling infections in home care and hospice.
AB  - The nursing bag has been used by home care visiting staff for decades to carry
      needed equipment and supplies to provide patient care in the home. The nursing
      bag is transported from patient home to home and may serve as a vehicle for
      transmitting microorganisms by virtue of the bag's contact with the staff's hands
      and contact with the patient's environment. This article establishes guidelines
      for the management of the nursing bag used by home care and hospice staff and
      offers strategies to prevent and control the transfer of microorganisms through
      its use. 

PMID- 24326475
TI  - Palliative wound care: principles of care.
AB  - Home care nursing occurs in a complex care environment. Nurses working in this
      setting care for a wide array of individuals who often are sicker and more
      complex than ever before. The high prevalence of wounds among these individuals
      requires that home care nurses have a certain level of knowledge to provide
      excellent care. Many times, individuals with wounds do not have the capacity to
      heal or are burdened with numerous symptoms affecting quality of life. In these
      cases, the home care nurse must understand concepts of palliative wound care to
      alleviate symptoms with the goal of improving quality of life. 

PMID- 24326477
TI  - Effectiveness of motivational interviewing to improve chronic condition self
      management: what does the research show us?
AB  - Motivational interviewing (MI) as a strategy to promote behavior change has its
      roots in the addiction field. In recent years there is growing use of MI as an
      intervention to help patients with diet, physical activity, and other lifestyle
      changes. This counseling approach initially developed by clinical psychologists
      is a goal-oriented, client-centered counseling style for eliciting behavior
      change by helping clients to explore and resolve ambivalence (). MI is appealing
      because it is seen as a practical front-line intervention that is concordant with
      patient-centered care that is being called for in the health service
      environment.This column profiles four published research/synthesis articles
      describing experiences by different groups in implementing MI strategies. As you
      will read, results from trials evaluating MI on patient outcomes are mixed and
      there continues to be gaps in the evidence on how to best implement MI and on
      which patients will most likely benefit. Even with outstanding questions, MI
      shows promise in the very challenging area of promoting behavior change and
      warrants continued investigation. Interested readers are encouraged to read the
      original articles for more details. 

PMID- 24326478
TI  - The new quality movement in hospice and palliative care: where is it going?

PMID- 24326480
TI  - Didactic Lecture Versus Interactive Workshop for Continuing Pharmacy Education on
      Reproductive Health: A Randomized Controlled Trial.
AB  - Pharmacists are routinely providing reproductive health counseling in community
      pharmacies, but studies have revealed significant deficits in their competencies.
      Therefore, continuing pharmacy education (CPE) could be utilized as a valuable
      modality to upgrade pharmacists' capabilities. A randomized controlled trial was
      designed to compare the efficacy of CPE meetings (lecture based vs. workshop
      based) on contraception and male sexual dysfunctions. Sixty pharmacists were
      recruited for each CPE meeting. Small group training using simulated patients was
      employed in the workshop-based CPE. Study outcomes were declarative/procedural
      knowledge, attitudes, and satisfaction of the participants. Data were collected
      pre-CPE, post-CPE, and 2 months afterward and were analyzed using repeated
      measure analysis of variance and Mann-Whitney U test. Results showed that lecture
      based CPE was more successful in improving pharmacists' knowledge post-CPE (p <
      .001). In contrast, a significant decrease was observed in the lecture-based
      group at follow-up (p = .002), whereas the workshop-based group maintained their
      knowledge over time (p = 1.00). Knowledge scores of both groups were
      significantly higher at follow-up in comparison with pre-CPE (p < .01). No
      significant differences were observed regarding satisfaction and attitudes scores
      between groups. In conclusion, an interactive workshop might not be superior to
      lecture-based training for improving pharmacists' knowledge and attitudes in a 1
      day CPE meeting. 

PMID- 24326479
TI  - In vivo postnatal electroporation and time-lapse imaging of neuroblast migration
      in mouse acute brain slices.
AB  - The subventricular zone (SVZ) is one of the main neurogenic niches in the
      postnatal brain. Here, neural progenitors proliferate and give rise to
      neuroblasts able to move along the rostral migratory stream (RMS) towards the
      olfactory bulb (OB). This long-distance migration is required for the subsequent
      maturation of newborn neurons in the OB, but the molecular mechanisms regulating
      this process are still unclear. Investigating the signaling pathways controlling
      neuroblast motility may not only help understand a fundamental step in
      neurogenesis, but also have therapeutic regenerative potential, given the ability
      of these neuroblasts to target brain sites affected by injury, stroke, or
      degeneration. In this manuscript we describe a detailed protocol for in vivo
      postnatal electroporation and subsequent time-lapse imaging of neuroblast
      migration in the mouse RMS. Postnatal electroporation can efficiently transfect
      SVZ progenitor cells, which in turn generate neuroblasts migrating along the RMS.
      Using confocal spinning disk time-lapse microscopy on acute brain slice cultures,
      neuroblast migration can be monitored in an environment closely resembling the in
      vivo condition. Moreover, neuroblast motility can be tracked and quantitatively
      analyzed. As an example, we describe how to use in vivo postnatal electroporation
      of a GFP-expressing plasmid to label and visualize neuroblasts migrating along
      the RMS. Electroporation of shRNA or CRE recombinase-expressing plasmids in
      conditional knockout mice employing the LoxP system can also be used to target
      genes of interest. Pharmacological manipulation of acute brain slice cultures can
      be performed to investigate the role of different signaling molecules in
      neuroblast migration. By coupling in vivo electroporation with time-lapse
      imaging, we hope to understand the molecular mechanisms controlling neuroblast
      motility and contribute to the development of novel approaches to promote brain
      repair. 

PMID- 24326481
TI  - Annular erythema in primary Sjogren's syndrome: description of 43 non-Asian
      cases.
AB  - OBJECTIVE: The objective of this paper is to evaluate the prevalence and
      characterize the main epidemiological, clinical and immunological features of
      annular erythema (AE) in non-Asian patients with primary Sjogren's syndrome (SS).
      METHODS: We carried out a retrospective study searching for AE in 377 Spanish
      patients with primary SS fulfilling the 2002 American-European criteria. In
      addition, we searched PubMed (1994-2012) using the MeSH terms "annular erythema"
      and "primary Sjogren's syndrome" for additional cases. All cases with AE reported
      in patients with SS associated with systemic lupus erythematosus were excluded.
      RESULTS: In our Spanish cohort, we found 35 (9%) patients diagnosed with AE. All
      were white females, with a mean age of 47 years at diagnosis of AE. AE preceded
      diagnosis of SS in 27 (77%) patients. Cutaneous AE lesions involved principally
      the face and upper extremities. All patients reported photosensitivity, with
      cutaneous flares being reported during the warmest months in 93% of patients.
      Immunological markers consisted of anti-Ro/La antibodies in 31 (89%) patients. In
      the literature search, we identified eight additional non-Asian patients with
      primary SS diagnosed with AE. In comparison with 52 Asian patients, the 43 non
      Asian patients with AE related to primary SS were more frequently women (100% vs
      78%, p=0.008), and cutaneous lesions were less frequently reported in the face
      (55% vs 81%, p=0.045) and more frequently in the neck (40% vs 14%, p=0.041).
      Immunologically, non-Asian patients had a lower frequency of anti-Ro antibodies
      and a higher frequency of negative Ro/La antibodies, although the differences
      were not statistically significant. CONCLUSION: AE is not an exclusive cutaneous
      feature of Asian patients with primary SS. In addition to the characteristic
      cutaneous expression, AE has a very specific clinical and immunological profile:
      often presenting before the fulfillment of SS criteria, overwhelmingly associated
      with anti-Ro antibodies but weakly associated with other immunological markers
      and the main systemic SS-related features.

PMID- 24326482
TI  - Trends in systemic lupus erythematosus mortality in Spain from 1981 to 2010.
AB  - BACKGROUND: Incidence and mortality of systemic lupus erythematosus (SLE) seem to
      be increasing in the last few decades, in contrast to the survival rate that has
      improved over time. The objective of this study was to examine the trends in the
      SLE mortality in Spain over a 30-year period (1981-2010). METHODS: Data on SLE
      deaths were drawn from the National Statistics Institute of Spain. Crude and
      overall age-standardized SLE mortality rates were calculated and joinpoint
      regression models were used to describe trend changes. Mean age of deaths by SLE
      each year was also assessed. RESULTS: The overall age-standardized SLE mortality
      rate was 1.82 per million in 1981 and 2.24 in 2010. It was higher in women, 1.39
      vs 0.43 in 1981 and 1.96 vs 0.28 in 2010. There was a statistically significant
      change in 1999. The overall age-standardized mortality rate increased from 1981
      to 1999 and stabilized from 2000 to 2010. Only male rates decreased from 2000 to
      2010. The mean age at death increased with time, from 42 years in 1981 to 61
      years in 2010. CONCLUSIONS: In conclusion, a slight decrease in SLE mortality has
      been observed in Spain over the last decade and future studies would be needed to
      explain the factors contributing to the improvement in the mortality rates.

PMID- 24326485
TI  - What happened to Dan Markingson?

PMID- 24326484
TI  - Dynamic behaviour of giant unilamellar vesicles induced by the uptake of
      [70]fullerene.
AB  - To obtain direct evidence for the fullerene-exchange reactions from the gamma
      cyclodextrin cavities to the lipid membranes following the addition of a
      C70.gamma-cyclodextrin complex, we monitored the dynamic behaviours of the giant
      unilamellar vesicles. A number of C70 aggregates generated in the lipid membranes
      moved about vigorously. 

PMID- 24326486
TI  - Unwanted pregnancies continue to be a major problem for women's health.

PMID- 24326487
TI  - [Apocalypse now?].

PMID- 24326488
TI  - [Nobel Prize for studies of vesicle transport].

PMID- 24326489
TI  - [The body's own signaling system--now as treatment].

PMID- 24326490
TI  - [New religiosity and the magical].

PMID- 24326491
TI  - [E. Meland replies].

PMID- 24326492
TI  - [Reservation without any inconvenience?].

PMID- 24326496
TI  - Poor title--poor manuscript?
AB  - BACKGROUND: The title of a scientific article is important for several reasons.
      Does the title of a manuscript submitted for publication in a medical journal
      reflect the quality of the manuscript itself? MATERIAL AND METHOD: We prepared
      criteria for poor, fair and good titles and tested them in pilot studies. All
      manuscripts submitted to the Journal of the Norwegian Medical Association during
      the period 1 September 2009-31 August 2011 as original articles (n = 211) or
      review articles (n = 110) were recorded. The quality of the titles was scored by
      two former editors. Primary outcome measures were rejection rates and odds ratio
      for rejection of manuscripts with a poor title compared to those with a good
      title. RESULTS: For original articles, the rejection rate for manuscripts with a
      poor, fair or good title amounted to 88%, 73% and 61% (p = 0.002) respectively,
      and for review articles 83%, 56% and 38% (p < 0.001). The odds ratio for
      rejection of manuscripts with a poor title compared to those with a good title
      was 4.6 (95% CI: 1.7-12.3) for original articles and 8.2 (95% CI: 2.6-26.4) for
      review articles. In a logistic regression model, the quality of the title
      explained 14% and 27% of the variance in outcome for original articles and review
      articles respectively. INTERPRETATION: In this study, a poor manuscript title was
      significantly associated with manuscript rejection. This indicates that the
      quality of the title often reflects the quality of the manuscript itself.

PMID- 24326497
TI  - [The Oslo96 reform and skills updating practices].
AB  - BACKGROUND: We have previously shown that 2-3 years after completion of their
      studies, doctors who had followed the study programme Oslo96 spent somewhat more
      time on updating their skills than other doctors trained at the University of
      Oslo, but less time than doctors trained at the University of Bergen. The purpose
      of this study is to investigate whether these differences had changed 5.5-7 years
      after graduation. MATERIAL AND METHOD: We used questionnaire data collected from
      the last cohort to follow the old programme of study at UiO (graduated 2001), the
      second cohort to follow the Oslo96 programme (graduated 2003) and the cohort that
      graduated from the University of Bergen in 2003. Data were collected 5.5-7 years
      after graduation (T2) and compared to corresponding data collected 2-3 years
      after graduation (T1). The study included only respondents who had answered all
      questions at both T1 and T2. RESULTS: The response rate ranged from 55% to 59% in
      the three samples. At 5.5-7 years after graduation we found no differences with
      regard to the time spent on updating between Oslo96 doctors (median: 230
      minutes/week) and doctors who had graduated before the Oslo96 reform or from the
      University of Bergen (median: 240 minutes/week in both groups). All three groups
      reported a statistically significant increase from T1 to T2 in their use of the
      Internet for purposes of skills updating. Training courses and conferences were
      the preferred forms of skills updating. INTERPRETATION: A correlation between the
      programme of study and the doctors' habits with regard to skills updating could
      not be detected.

PMID- 24326498
TI  - Catheter retained in the brain.

PMID- 24326499
TI  - [A man in his 70s found confused on his training ride].

PMID- 24326500
TI  - [Metabolic acidosis--not always easy].

PMID- 24326501
TI  - "I'm a Norwegian doctor"--a quotation with a life of its own.

PMID- 24326502
TI  - Dead infants and unmarried women--from forensic pathology reports 1910-12.
AB  - The lack of access to contraceptives and poor control over their own pregnancies
      represented a major problem for women 100 years ago. An unwanted pregnancy could
      lead to social exclusion and loss of paid work, and clandestine births and
      infanticide thus posed a social problem. A review of the archives of the
      Norwegian Board of Forensic Medicine in the period 1910 to 1912 shows that one
      fifth of all expert opinions were related to infants and pregnancy. Autopsies
      performed on children constituted over one-third of all forensic autopsies during
      this period. Although the reports provide a timely reminder of the value of hard
      earned rights in Norway, the lack of control over their own sexuality and
      unwanted pregnancies are unfortunately still the reality for a large proportion
      of the world's women.

PMID- 24326503
TI  - "The child has lived and breathed." Forensic examinations of newborns 1910-1912.
AB  - One hundred years ago, forensic examination of deceased infants was not an
      uncommon task for doctors in Norway. The key questions were whether the infant
      had been born alive and whether the manner of death could be explained. The
      decomposition of the corpses, which had often lain hidden long before they were
      examined, posed a considerable problem. Notwithstanding the known shortcomings in
      the criteria used for assessment of breathing (the lung flotation test), and the
      fact that the bodies were often severely decomposed, the lung flotation test and
      the supposed signs of asphyxiation were used indiscriminately. This absence of
      association between theoretical knowledge and practice may have had its origin in
      societal conditions in which clandestine birth and the killing of newborns was
      not uncommon.

PMID- 24326504
TI  - [The history of antibiotics].
AB  - The development of chemical compounds for the treatment of infectious diseases
      may be divided into three phases: a) the discovery in the 1600s in South America
      of alkaloid extracts from the bark of the cinchona tree and from the dried root
      of the ipecacuanha bush, which proved effective against, respectively, malaria
      (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs,
      which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915)
      discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964)
      discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The
      prime example of the latter is the development of penicillin in the late 1920s
      following a discovery by a solitary research scientist who never worked in a team
      and never as part of a research programme. It took another ten years or so before
      drug-quality penicillin was produced, with research now dependent on being
      conducted in large collaborative teams, frequently between universities and
      wealthy industrial companies. The search for new antibiotics began in earnest in
      the latter half of the 1940s and was mostly based on soil microorganisms. Many
      new antibiotics were discovered in this period, which may be termed "the golden
      age of antibiotics". Over the past three decades, the development of new
      antibiotics has largely stalled, while antibiotic resistance has increased. This
      situation may require new strategies for the treatment of infectious diseases.

PMID- 24326505
TI  - Jacob Aall's illness and death.
AB  - Jacob Aall (1773-1844) was one of Norway's most notable nation-builders at the
      beginning of the 19th century. He owned and operated a large ironworks,
      participated in political life and was an historian, writer and translator of
      sagas. In the last 15 years of his life, he suffered greatly from pain attacks.
      After his death, an autopsy was performed and the doctors found a stone the size
      of a hen's egg, which weighed more than 90 g. The stone was variously described
      as a kidney stone and a bladder stone. Aall had travelled to Copenhagen in 1837
      and consulted the Danish doctor Ludvig Levin Jacobson (1783-1843), known for his
      instrument for crushing bladder stones, a new and revolutionary treatment method.
      But some disagreement appears to have arisen between them about the treatment. A
      year later Aall consulted Christen Heiberg (1799-1872), a professor of surgery in
      Christiania (now Oslo). Heiberg also examined Aall's bladder and found "no cause
      for alarm". Aall adhered to a strict diet, including drinking an Italian "spa
      water" daily which he obtained in bottles from Trieste. However, he showed no
      great improvement. To all appearances, it was kidney stones that afflicted him in
      his last years and which finally ended his life. This article gives a full
      portrayal of the course of his illness with an authentic description from an age
      when there were no treatment possibilities for kidney stones.

PMID- 24326506
TI  - Christiansen's artificial hip joints--what went wrong?
AB  - Modern arthroplasty is undoubtedly the greatest contribution that orthopaedic
      surgery has ever made to medical science. The honour for the good results
      achieved with total hip replacement surgery goes chiefly to the Briton John
      Charnley (1911-1982). However, the Norwegian Tor Aas Christiansen (1917-1981) has
      also earned a place in this history. He wanted to improve the operative treatment
      of dislocated, medial fractures of the femoral neck, and in the 1960s he
      constructed a hemiprosthesis. Later, he also made a total prosthesis for the hip
      joint. Over time, the prostheses proved to be less than successful. Nevertheless,
      approximately 6,500 Christiansen prostheses were fitted in Norway before a
      prospective Charnley vs. Christiansen study at the Coastal Hospital in Hagavik
      finally put an end to his prostheses in 1983. Indirectly, the study led to the
      establishment of a national register of hip prostheses, now the National
      Arthroplasty Register, at Haukeland University Hospital. Based on our personal
      cooperation with Christiansen, as well as original drawings and correspondence
      from the Polaris factory in Sandnes, we will tell the story of Christiansen's
      hemi- and total prostheses. These are a key element in the history of hip
      arthroplasty in Norway.

PMID- 24326507
TI  - [Inadequate transportation of patients].

PMID- 24326508
TI  - [An expected effect].

PMID- 24326509
TI  - Emeritus, emerita--or simply retired?

PMID- 24326514
TI  - Wnt1-regulated genetic networks in midbrain dopaminergic neuron development.
AB  - Neurons synthesizing the neurotransmitter dopamine exert crucial functions in the
      mammalian brain. The biggest and most important population of dopamine
      synthesizing neurons is located in the mammalian ventral midbrain (VM), and
      controls and modulates the execution of motor, cognitive, affective,
      motivational, and rewarding behaviours. Degeneration of these neurons leads to
      motor deficits that are characteristic of Parkinson's disease, while their
      dysfunction is involved in the pathogenesis of psychiatric disorders including
      schizophrenia and addiction. Because the aetiology and therapeutic prospects for
      these diseases include neurodevelopmental aspects, substantial scientific
      interest has been focused on deciphering the mechanistic pathways that control
      the generation and survival of these neurons during embryonic development.
      Researches during the last decade revealed the pivotal role of the secreted Wnt1
      ligand and its signalling cascade in the generation of the dopamine-synthesizing
      neurons in the mammalian VM. Here, we summarize the initial and more recent
      findings that have unravelled several Wnt1-controlled genetic networks required
      for the proliferation and commitment of VM progenitors to the dopaminergic cell
      fate during midgestational embryonic stages, and for the correct differentiation
      of these progenitors into postmitotic dopamine-synthesizing neurons at late
      midgestational embryonic and foetal stages. 

PMID- 24326515
TI  - Lateralized cortical involvement and contralateral parkinsonism without basal
      ganglia involvement in two autopsy cases of corticobasal syndrome-Alzheimer's
      disease.
AB  - Corticobasal syndrome (CBS) is characterized by lateralized motor disturbance due
      to levodopa nonresponsive parkinsonism and progressive apraxia. Although CBS is
      neuropathologically heterogeneous, it remains unclear whether the clinical
      features of all CBS cases are the same. We report two autopsy cases diagnosed
      clinically as CBS and pathologically as Alzheimer's disease characterized by
      lateralized cerebral cortical degeneration and absence of significant
      nigrostriatial lesions. Cerebral cortical degeneration in both cases was
      contralateral to their motor disturbances. Thus, nigrostriatial lesions and
      contralateral cerebral cortical lesions can cause motor disturbances in CBS,
      necessitating the need for bedside examination in patients with CBS. 

PMID- 24326516
TI  - No differences in hippocampal volume between carriers and non-carriers of the
      ApoE epsilon4 and epsilon2 alleles in young healthy adolescents.
AB  - Alleles of the apolipoprotein E (ApoE) gene are known to modulate the genetic
      risk for developing late-onset Alzheimer's disease (AD) and have been associated
      with hippocampal volume differences in AD. However, the effect of these alleles
      on hippocampal volume in younger subjects has yet to be clearly established.
      Using a large cohort of more than 1,400 adolescents, this study found no
      hippocampal volume or hippocampal asymmetry differences between carriers and non
      carriers of the ApoE epsilon4 or epsilon2 alleles, nor dose-dependent effects of
      either allele, suggesting that regionally specific effects of these polymorphisms
      may only become apparent in later life. 

PMID- 24326517
TI  - TFP5, a peptide derived from p35, a Cdk5 neuronal activator, rescues cortical
      neurons from glucose toxicity.
AB  - Multiple lines of evidence link the incidence of diabetes to the development of
      Alzheimer's disease (AD). Patients with diabetes have a 50 to 75% increased risk
      of developing AD. Cyclin dependent kinase 5 (Cdk5) is a serine/threonine protein
      kinase, which forms active complexes with p35 or p39, found principally in
      neurons and in pancreatic beta cells. Recent studies suggest that Cdk5
      hyperactivity is a possible link between neuropathology seen in AD and diabetes.
      Previously, we identified P5, a truncated 24-aa peptide derived from the Cdk5
      activator p35, later modified as TFP5, so as to penetrate the blood-brain barrier
      after intraperitoneal injections in AD model mice. This treatment inhibited
      abnormal Cdk5 hyperactivity and significantly rescued AD pathology in these mice.
      The present study explores the potential of TFP5 peptide to rescue high glucose
      (HG)-mediated toxicity in rat embryonic cortical neurons. HG exposure leads to
      Cdk5-p25 hyperactivity and oxidative stress marked by increased reactive oxygen
      species production, and decreased glutathione levels and superoxide dismutase
      activity. It also induces hyperphosphorylation of tau, neuroinflammation as
      evident from the increased expression of inflammatory cytokines like TNF-alpha,
      IL-1beta, and IL-6, and apoptosis. Pretreatment of cortical neurons with TFP5
      before HG exposure inhibited Cdk5-p25 hyperactivity and significantly attenuated
      oxidative stress by decreasing reactive oxygen species levels, while increasing
      superoxide dismutase activity and glutathione. Tau hyperphosphorylation,
      inflammation, and apoptosis induced by HG were also considerably reduced by
      pretreatment with TFP5. These results suggest that TFP5 peptide may be a novel
      candidate for type 2 diabetes therapy.

PMID- 24326518
TI  - Natural history of functional decline in Alzheimer's disease: a systematic
      review.
AB  - BACKGROUND: Knowledge of functional evolution in dementia is crucial for the
      patients and their families as well as the clinician. OBJECTIVE: This review
      identifies scales and outcomes used to describe the natural history of functional
      decline and describes the natural history of functional decline in a
      representative clinical population sample of published studies of patients with
      Alzheimer's disease (AD). METHODS: A search of three relevant databases was
      conducted and limited to articles published in English and French between 1998 to
      March 2012, using the keywords "Dementia", "Activities of Daily Living",
      "Instrumental Activities of Daily Living", "Functional Impairment", "Prognosis",
      and "Disease Progression". RESULTS: The search strategy displayed 683 articles,
      20 of which were found to be related to the functional evolution of AD. In these
      studies, different scales were used to describe the evolution of the functional
      decline, except for the decline of instrumental activities, for which the Lawton
      scale was used in all studies. Thus, it is difficult to represent the evolution
      of the functional decline from a clinical point of view. CONCLUSION: Relatively
      little data are available to estimate the functional evolution of AD. A consensus
      with broadened thought is required to know if the progression of the incapacities
      in these scales is additive or hierarchical.

PMID- 24326520
TI  - Estrogen receptor beta variants modify risk for Alzheimer's disease in a
      multiethnic female cohort.
AB  - BACKGROUND: Few studies of gene variants that affect estrogen activity
      investigate their association with age at onset of Alzheimer's disease (AD) in
      women of different ethnicities. We investigated the influence of ESR2
      polymorphisms on age at onset of AD in a multiethnic cohort of women. OBJECTIVES:
      To determine whether gene variants would affect risk for AD differently in women
      of different population ancestries. METHODS: Among 1,686 women participating in
      the Washington Heights Inwood Columbia Aging Project (WHICAP), association with
      risk for AD was assessed for 20 ESR2 single-nucleotide polymorphisms (SNPs) using
      multivariate logistic regression, adjusting for age at time of study enrollment,
      presence of an APOE epsilon4 allele, years of education, and body mass index.
      RESULTS: Increased risk for AD was associated with four ESR2 SNPs in women of
      predominantly Caucasian AIMS-defined ancestry: rs944045, rs1256062, rs10144225,
      and rs2274705 (OR range 1.6-1.9, empiric p-value range 0.002-0.004). A separate
      SNP (rs10137185) was associated with decreased risk for AD in women who
      identified themselves as Black (OR 0.6, 95% CI = 0.4-0.9). When vascular risk
      factors were included in the model, a separate SNP (rs1256059) was associated
      with increased risk for AD in women of admixed/Hispanic ancestry (OR 1.5, 95% CI
      = 1.1-2.4). CONCLUSIONS: ESR2 polymorphisms affect risk for AD in women, and risk
      alleles vary by AIMs-defined ancestry and self-identified ethnicity. These
      effects are possibly due to different linkage disequilibrium patterns or
      differences in comorbid risk factors mediating SNP effect on risk for AD by
      group.

PMID- 24326521
TI  - Bisphenol A does not affect memory performance in adult male rats.
AB  - Bisphenol A (BPA) is an estrogenic endocrine disruptor used for producing
      polycarbonate plastics and epoxy resins. This study investigated the effects of
      oral BPA administration on memory performance, general activity, and emotionality
      in adult male Sprague Dawley rats using a battery of behavioral tests, including
      an appetite-motivated maze test (MAZE test) used to assess spatial memory
      performance. In addition, in order to confirm the effects of BPA on spatial
      memory performance, we examined whether intrahippocampal injection of BPA affects
      spatial memory consolidation. In the MAZE test, although oral BPA administration
      at 10 mg/kg significantly altered the number of entries into the incorrect area
      compared to those of vehicle-treated rats, male rats given BPA through either
      oral administration or intrahippocampal injection failed to show significant
      differences in latencies to reach the reward. Also, oral BPA administration did
      not affect fear-motivated memory performance in the step-through passive
      avoidance test. Oral BPA administration at 0.05 mg/kg, the lowest dose used in
      this study, was correlated with a decrease in locomotor activity in the open
      field test, whereas oral administration at 10 mg/kg, the highest dose used in
      this study, was correlated with a light anxiolytic effect in the elevated plus
      maze test. The present study suggests that BPA in adulthood has little effect on
      spatial memory performance in male rats.

PMID- 24326519
TI  - Late-onset Alzheimer's disease, heating up and foxed by several proteins:
      pathomolecular effects of the aging process.
AB  - Late-onset Alzheimer's disease (LOAD) is the most common neurodegenerative
      disorder in older adults, affecting over 50% of those over age 85. Aging is the
      most important risk factor for the development of LOAD. Aging is associated with
      the decrease in the ability of cells to cope with cellular stress, especially
      protein aggregation. Here we describe how the process of aging affects pathways
      that control the processing and degradation of abnormal proteins including
      amyloid-beta (Abeta). Genetic association studies in LOAD have successfully
      identified a large number of genetic variants involved in the development of the
      disease. However, there is a gap in understanding the interconnections between
      these pathomolecular events that prevent us from discovering therapeutic targets.
      We propose novel, pertinent links to elucidate how the biology of aging affects
      the sequence of events in the development of LOAD. Furthermore we analyze and
      synthesize the molecular-pathologic-clinical correlations of the aging process,
      involving the HSF1 and FOXO family pathways, Abeta metabolic pathway, and the
      different clinical stages of LOAD. Our new model postulates that the aging
      process would precede Abeta accumulation, and attenuation of HSF1 is an
      "upstream" event in the cascade that results in excess Abeta and synaptic
      dysfunction, which may lead to cognitive impairment and/or trigger "downstream"
      neurodegeneration and synaptic loss. Specific host factors, such as the activity
      of FOXO family pathways, would mediate the response to Abeta toxicity and the
      pace of progression toward the clinical manifestations of AD. 

PMID- 24326523
TI  - Gold nanoparticle-decorated graphene oxides for plasmonic-enhanced polymer
      photovoltaic devices.
AB  - In this work, gold nanoparticle/graphene oxide (AuNP/GO) nanocomposites are
      synthesized and used as anodic buffer layers in organic photovoltaic devices
      (OPVs). The application of thiol-terminated polyethylene glycol as a capping
      agent prevents the aggregation of AuNPs on the GO surface and further improves
      the solubility and stability of these nanomaterials in solutions. When AuNP/GO
      nanomaterials served as the buffer layers, they introduced localized surface
      plasmon resonance (LSPR) in the OPVs, leading to noticeable enhancements in the
      photocurrent and the efficiencies of the OPVs. We attribute the primary origin of
      the improvement in device performance to local field enhancement induced by the
      LSPR. We anticipate that this study might open up new avenues for constructing
      plasmon-enhancing layers on the nanoscale to improve the performance of solar
      cells. 

PMID- 24326522
TI  - Aminoguanidine changes hippocampal expression of apoptosis-related genes,
      improves passive avoidance learning and memory in streptozotocin-induced diabetic
      rats.
AB  - Cognitive dysfunction occurs in patients with diabetes mellitus. The objective of
      this study was to examine whether bilateral intrahippocampal CA1 (intra-CA1)
      injection of aminoguanidine (AG) can either affect the Bcl-2 family gene
      expression or reduce the diabetic imposing abnormalities of passive avoidance
      learning (PAL) and memory. Rats were divided into five groups: control (C),
      control treated with normal saline (CS), control treated with AG (S-AG),
      diabetics (D), and diabetics treated with AG (D-AG). Diabetes mellitus was
      induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg).
      AG (30 MUg/rat) or vehicle was administered intra-CA1 bilaterally at the onset of
      hyperglycemia. PAL was assessed 7 weeks later. Animals were killed, and
      hippocampus was dissected following the behavioral test. The expressions of Bax,
      Bcl-2, and Bcl-xl mRNAs were measured using semiquantitative RT-PCR technique.
      The result of passive avoidance task showed that AG significantly improved the
      cognitive performance in diabetic rats. Moreover, AG treatment decreased the
      levels of Bcl-2 and Bcl-xL expressions in diabetic group. The ratio of Bax/Bcl-2
      and Bax/Bcl-xL decreased significantly in AG-treated diabetic animals. In
      conclusion, initial treatment with AG by intra-CA1 micro-injection improves the
      impaired passive avoidance task in STZ-induced diabetic rats which may be related
      to the decreased Bax/Bcl-2 and Bax/Bcl-xL ratios.

PMID- 24326524
TI  - Maspin and it's evolving role in tumor progression in systemic malignancies.

PMID- 24326525
TI  - In reply: maspin and it's evolving role in tumor progression in systemic
      malignancies.

PMID- 24326527
TI  - Pancreatic beta cell function following liraglutide-augmented weight loss in
      individuals with prediabetes: analysis of a randomised, placebo-controlled study.
AB  - AIMS/HYPOTHESIS: Liraglutide can modulate insulin secretion by directly
      stimulating beta cells or indirectly through weight loss and enhanced insulin
      sensitivity. Recently, we showed that liraglutide treatment in overweight
      individuals with prediabetes (impaired fasting glucose and/or impaired glucose
      tolerance) led to greater weight loss (-7.7% vs -3.9%) and improvement in insulin
      resistance compared with placebo. The current study evaluates the effects on beta
      cell function of weight loss augmented by liraglutide compared with weight loss
      alone. METHODS: This was a parallel, randomised study conducted in a single
      academic centre. Both participants and study administrators were blinded to
      treatment assignment. Individuals who were 40-70 years old, overweight (BMI 27-40
      kg/m(2)) and with prediabetes were randomised (via a computerised system) to
      receive liraglutide (n = 35) or matching placebo (n = 33), and 49 participants
      were analysed. All were instructed to follow an energy-restricted diet. Primary
      outcome was insulin secretory function, which was evaluated in response to graded
      infusions of glucose and day-long mixed meals. RESULTS: Liraglutide treatment (n
      = 24) significantly (p <= 0.03) increased the insulin secretion rate (% mean
      change [95% CI]; 21% [12, 31] vs -4% [-11, 3]) and pancreatic beta cell
      sensitivity to intravenous glucose (229% [161, 276] vs -0.5% (-15, 14]), and
      decreased insulin clearance rate (-3.5% [-11, 4] vs 8.2 [0.2, 16]) as compared
      with placebo (n = 25). The liraglutide-treated group also had significantly (p <=
      0.03) lower day-long glucose (-8.2% [-11, -6] vs -0.1 [-3, 2]) and NEFA
      concentrations (-14 [-20, -8] vs -2.1 [-10, 6]) following mixed meals, whereas
      day-long insulin concentrations did not significantly differ as compared with
      placebo. In a multivariate regression analysis, weight loss was associated with a
      decrease in insulin secretion rate and day-long glucose and insulin
      concentrations in the placebo group (p <= 0.05), but there was no association
      with weight loss in the liraglutide group. The most common side effect of
      liraglutide was nausea. CONCLUSIONS/INTERPRETATION: A direct stimulatory effect
      on beta cell function was the predominant change in liraglutide-augmented weight
      loss. These changes appear to be independent of weight loss. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01784965 FUNDING: The study was funded by the ADA.

PMID- 24326528
TI  - Construction of a genetic map based on high-throughput SNP genotyping and genetic
      mapping of a TuMV resistance locus in Brassica rapa.
AB  - Brassica rapa is a member of the Brassicaceae family and includes vegetables and
      oil crops that are cultivated worldwide. The introduction of durable resistance
      against turnip mosaic virus (TuMV) into agronomically important cultivars has
      been a significant challenge for genetic and horticultural breeding studies of B.
      rapa. Based on our previous genome-wide analysis of DNA polymorphisms between the
      TuMV-resistant doubled haploid (DH) line VC40 and the TuMV-susceptible DH line
      SR5, we constructed a core genetic map of the VCS-13M DH population, which is
      composed of 83 individuals derived from microspore cultures of a F1 cross between
      VC40 and SR5, by analyzing the segregation of 314 sequence-characterized genetic
      markers. The genetic markers correspond to 221 SNPs and 31 InDels of genes as
      well as 62 SSRs, covering 1,115.9 cM with an average distance of 3.6 cM between
      the adjacent marker loci. The alignment and orientation of the constructed map
      showed good agreement with the draft genome sequence of Chiifu, thus providing an
      efficient strategy to map genic sequences. Using the genetic map, a novel
      dominant TuMV resistance locus (TuMV-R) in the VCS-13M DH population was
      identified as a 0.34 Mb region in the short arm of chromosome A6 in which four CC
      NBS-LRR resistance genes and two pathogenesis-related-1 genes reside. The genetic
      map developed in this study can play an important role in the genetic study of
      TuMV resistance and the molecular breeding of B. rapa.

PMID- 24326529
TI  - Evaluation of stationary colposcope and the Gynocular, by the Swede score
      systematic colposcopic system in VIA positive women: a crossover randomized
      trial.
AB  - OBJECTIVE: This study aimed to evaluate cervical lesions by the Swede coloscopy
      system, histologic finding, liquid-based cytology, and human papillomavirus (HPV)
      in women who resulted positive for visual inspection of the cervix with acetic
      acid (VIA) by using a pocket-sized battery-driven colposcope, the Gynocular
      (Gynius AB, Sweden). METHODS: This study was a crossover, randomized clinical
      trial at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University in
      Dhaka, Bangladesh, with 540 VIA-positive women. Swede scores were obtained by the
      Gynocular and stationary colposcope, as well as samples for liquid-based
      cytology, HPV, and cervical biopsies. The Swede scores were compared against the
      histologic diagnosis and used as criterion standard. The percentage agreement and
      the kappa statistic for the Gynocular and standard colposcope were also
      calculated. RESULTS: The Gynocular and stationary colposcope showed high
      agreement in Swede scores with a kappa statistic of 0.998, P value of less than
      0.0001, and no difference in detecting cervical lesions in biopsy. Biopsy
      detected cervical intraepithelial neoplasia (CIN) 2+ (CIN2, CIN3, and invasive
      cancer) in 38 (7%) of the women, whereas liquid-based cytology detected CIN2+ in
      13 (2.5%) of the women. Forty-four (8.6%) women who were tested resulted positive
      for HPV; 20 (3.9%) women had HPV-16, 2 (0.4%) had HPV-18, and 22 (4.3%) had other
      high-risk HPV. CONCLUSIONS: Our study showed that few VIA-positive women had
      CIN2+ lesions or HPV infection. Colposcopy by Swede score identified
      significantly more CIN2+ lesions than liquid-based cytology and could offer a
      more accurate screening and selection for immediate treatment of cervical lesions
      in low-resource settings.

PMID- 24326530
TI  - 1-Methyl-4-phenylpyridinium-induced cell death via autophagy through a Bcl
      2/Beclin 1 complex-dependent pathway.
AB  - Several lines of evidence suggest that the mechanism underlying drug-induced
      neuronal apoptosis is initiated by the increased production of reactive oxygen
      species (ROS). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin,
      has been shown to initiate an apoptotic cascade by increasing ROS in the
      dopaminergic neurons of the substantia nigra, leading to the morphological and
      physiological features associated with Parkinson's disease. Recently, it has been
      reported that autophagy, a type of programmed cell death independent of the
      apoptotic cascade, also plays a role in neuronal damage. Although autophagy is
      negatively regulated by the mammalian target of rapamycin receptor (mTOR), there
      is some evidence showing a novel function for the anti-apoptotic protein Bcl-2.
      Bcl-2 is proposed to play a role in negatively regulating autophagy by blocking
      an essential protein in the signaling pathway, Beclin 1. Nevertheless, it is
      unclear whether autophagy is also correlated with apoptotic signaling in 1-methyl
      4-phenylpyridinium (MPP(+)) toxicity. Therefore, we hypothesized that the MPP(+)
      toxicity generally associated with initiating the apoptotic signaling cascade
      also increases an autophagic phenotype in neuronal cells. Using the SK-N-SH
      dopaminergic cell lines, we demonstrate that MPP(+) increases the expression of
      microtubule-associated protein light chain 3 (LC3-II), an autophagosome membrane
      marker and the mTOR signaling pathway, and Beclin 1 while decreasing the Bcl-2
      levels. Moreover, these expressions correlate with a decreased binding ratio
      between Bcl-2 and Beclin 1, in effect limiting the regulation of the downstream
      autophagic markers, such as LC3-II. Our results indicate that MPP(+) can induce
      autophagy in SK-N-SH cells by decreasing the Bcl-2/Beclin 1 complex. 

PMID- 24326531
TI  - Association between Alzheimer disease and the -491T allele of regulatory region
      polymorphism of Apolipoprotein E in a Tunisian population.
AB  - The apolipoprotein E (APOE) is a well-established risk factor for late-onset
      Alzheimer's disease (AD). Several studies have attempted to confirm the
      association between the polymorphism located at position -491 in the
      transcriptional regulatory region of the APOE gene and AD. We examined in 85 AD
      patients and 90 control subjects of a Tunisian population the potential
      involvement of this polymorphism as a risk factor for AD, either through an
      independent effect or through interaction with the existing APOE epsilon4 allele
      risk. The T allele frequency was significantly higher in the AD patients group
      (45.3 %) than in the controls group (32.78 %) and may possibly constitute a
      significant risk factor for AD. The APOE epsilon4 allele did not influence the
      distribution of the -491 polymorphism after stratification. 

PMID- 24326532
TI  - Coaxial guide wire placement in the right adrenal vein for repeated adrenal
      venous samplings.
AB  - PURPOSE: Many adrenal venous sampling (AVS) protocols require repeated samplings
      before and after adrenocorticotrophic hormone (ACTH) stimulation. Maintaining
      catheter selectivity in the adrenal vein over time is essential but can be
      challenging, especially in the short right adrenal vein, where the catheter is
      often in an unstable position. The aim of our study was to evaluate guide wire
      insertion into the right adrenal vein catheter to sustain AVS selectivity
      (adrenal/peripheral cortisol ratio [Ca/Cp]) over time. METHODS: This
      retrospective investigation was approved by our institutional review board, and
      informed consent was obtained. A 0.014-inch guide wire was inserted in the right
      adrenal vein 5F catheter to secure its positioning and to facilitate blood
      sampling. Plasma cortisol levels from the left and right adrenal veins and left
      iliac vein were assessed in 117 consecutive patients undergoing bilateral,
      simultaneous sets of AVS at -5 and 0 min (baseline) and 5, 10, and 15 min after
      intravenous bolus of 250 MUg ACTH (stimulated). Ca/Cp ratios of >=2 for baseline
      and >10 for stimulated AVS were considered selective. RESULTS: The first
      sampling, at time -5 min, was nonselective in 41 of 116 (35.3 %) right and 30 of
      116 (25.9 %) left AVSs retained for analysis. In patients with a selective first
      sampling, 74 of 75 (98.7 %) right and 85 of 86 (98.8 %) left AVSs were selective
      in all post-ACTH samplings. Right and left selectivity rates were not
      statistically different (p > 0.87). No complications arose from guide wire
      insertion. CONCLUSION: Guide wire insertion into the right adrenal vein catheter
      is safe and effective to maintain AVS selectivity over time.

PMID- 24326533
TI  - Nature and consequences of non-covalent interactions between flavonoids and
      macronutrients in foods.
AB  - Many of the potential health benefits of flavonoids have been associated with
      their specific chemical and biological properties including their ability to
      interact and bind non-covalently to macronutrients in foods. While flavonoid
      protein interactions and binding have been the subject of intensive study,
      significantly less is understood about non-covalent interactions with
      carbohydrates and lipids. These interactions with macronutrients are likely to
      impact both the flavonoid properties in foods, such as their radical scavenging
      activity, and the food or beverage matrix itself, including their taste, texture
      and other sensorial properties. Overall, non-covalent binding of flavonoids with
      macronutrients is primarily driven by van der Waals interactions. From the
      flavonoid perspective, these interactions are modulated by characteristics such
      as degree of polymerization, molecular flexibility, number of external hydroxyl
      groups, or number of terminal galloyl groups. From the macronutrient standpoint,
      electrostatic and ionic interactions are generally predominant with
      carbohydrates, while hydrophobic interactions are generally predominant with
      lipids and mainly limited to interactions with flavonols. All of these
      interactions are involved in flavonoid-protein interactions. While primarily
      associated with undesirable characteristics in foods and beverages, such as
      astringency, negative impact on macronutrient digestibility and hazing, more
      recent efforts have attempted to leverage these interactions to develop
      controlled delivery systems or strategies to enhance flavonoids bioavailability.
      This paper aims at reviewing the fundamental bases for non-covalent interactions,
      their occurrence in food and beverage systems and their impact on the physico
      chemical, organoleptic and some nutritional properties of food. 

PMID- 24326534
TI  - Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells
      as monotherapy and in combination with anti-CD20 antibodies.
AB  - Natural killer (NK) cells mediate antilymphoma activity by spontaneous
      cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) when
      triggered by rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat
      patients with B-cell lymphomas. The balance of inhibitory and activating signals
      determines the magnitude of the efficacy of NK cells by spontaneous cytotoxicity.
      Here, using a killer-cell immunoglobulin-like receptor (KIR) transgenic murine
      model, we show that blockade of the interface of inhibitory KIRs with major
      histocompatibility complex (MHC) class I antigens on lymphoma cells by anti-KIR
      antibodies prevents a tolerogenic interaction and augments NK-cell spontaneous
      cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR treatment induces
      enhanced NK-cell-mediated, rituximab-dependent cytotoxicity against lymphoma in
      vitro and in vivo in KIR transgenic and syngeneic murine lymphoma models. These
      results support a therapeutic strategy of combination rituximab and KIR blockade
      through lirilumab, illustrating the potential efficacy of combining a tumor
      targeting therapy with an NK-cell agonist, thus stimulating the postrituximab
      antilymphoma immune response. 

PMID- 24326535
TI  - Evaluation and treatment of childhood physical abuse and neglect: a review.
AB  - According to 2010 CDC estimates, 1 in 5 US children have experienced
      maltreatment. Risk factors for child maltreatment include child characteristics
      such as non-compliance and diagnostic conditions that increase caregiver burden.
      Parent characteristic risk factors include parental mental illness and low social
      support. New developments in radiologic evaluation of child maltreatment will be
      reviewed. New findings in evidence based psychotherapies for childhood
      maltreatment will be discussed. A review of the role of pharmacotherapy in child
      maltreatment cases will also be presented. New evidence from prevention models
      targeting young mothers and families are also reviewed. 

PMID- 24326537
TI  - Electronic recording and reporting system for tuberculosis in China: experience
      and opportunities.
AB  - Tuberculosis (TB) surveillance in China is organized through a nationwide network
      of about 3200 hospitals and health facilities. In 2005, an electronic
      Tuberculosis Information Management System (TBIMS) started to be phased in to
      replace paper recording. The TBIMS collects key information on TB cases notified
      in TB care facilities, and exchanges real-time data with the Infectious Disease
      Reporting System, which covers the country's 37 notifiable diseases. The system
      is accessible to authorized users at every level of the TB network through a
      password-protected website. By 2009 the TBIMS achieved nationwide coverage.
      Completeness of data on patient bacteriological end points improved remarkably
      over time. Data on about a million active TB cases, including drug-resistant TB,
      are included each year. The sheer scale of the data handling and the intricate
      functions that the China TBIMS performs makes it stand apart from the electronic
      information systems for TB adopted in other countries. 

PMID- 24326536
TI  - Personal health records: a randomized trial of effects on elder medication
      safety.
AB  - PURPOSE: To examine the impact of a personal health record (PHR) on medication
      use safety among older adults. BACKGROUND: Online PHRs have potential as tools to
      manage health information. We know little about how to make PHRs accessible for
      older adults and what effects this will have. METHODS: A PHR was designed and
      pretested with older adults and tested in a 6-month randomized controlled trial.
      After completing mailed baseline questionnaires, eligible computer users aged 65
      and over were randomized 3:1 to be given access to a PHR (n=802) or serve as a
      standard care control group (n=273). Follow-up questionnaires measured change
      from baseline medication use, medication reconciliation behaviors, and medication
      management problems. RESULTS: Older adults were interested in keeping track of
      their health and medication information. A majority (55.2%) logged into the PHR
      and used it, but only 16.1% used it frequently. At follow-up, those randomized to
      the PHR group were significantly less likely to use multiple non-steroidal anti
      inflammatory drugs-the most common warning generated by the system (viewed by 23%
      of participants). Compared with low/non-users, high users reported significantly
      more changes in medication use and improved medication reconciliation behaviors,
      and recognized significantly more side effects, but there was no difference in
      use of inappropriate medications or adherence measures. CONCLUSIONS: PHRs can
      engage older adults for better medication self-management; however, features that
      motivate continued use will be needed. Longer-term studies of continued users
      will be required to evaluate the impact of these changes in behavior on patient
      health outcomes.

PMID- 24326539
TI  - Introduction to innovations in the immunology and clinical science of alopecia
      areata.
AB  - Alopecia areata is an autoimmune skin disease resulting in the loss of hair on
      the scalp and elsewhere on the body. The disease most often occurs in childhood
      and affects males and females of all ages. The National Alopecia Areata
      Foundation conducts research summits every 2 years to review progress and create
      new directions in its funded and promoted research. The Foundation brings
      together scientists from all disciplines to get a broad and varied perspective.
      These summits are part of the Foundation's main strategic initiative, the
      Alopecia Areata Treatment Development Program to accelerate progress toward a
      viable alopecia areata treatment. 

PMID- 24326538
TI  - Heart beats in the cloud: distributed analysis of electrophysiological 'Big Data'
      using cloud computing for epilepsy clinical research.
AB  - OBJECTIVE: The rapidly growing volume of multimodal electrophysiological signal
      data is playing a critical role in patient care and clinical research across
      multiple disease domains, such as epilepsy and sleep medicine. To facilitate
      secondary use of these data, there is an urgent need to develop novel algorithms
      and informatics approaches using new cloud computing technologies as well as
      ontologies for collaborative multicenter studies. MATERIALS AND METHODS: We
      present the Cloudwave platform, which (a) defines parallelized algorithms for
      computing cardiac measures using the MapReduce parallel programming framework,
      (b) supports real-time interaction with large volumes of electrophysiological
      signals, and (c) features signal visualization and querying functionalities using
      an ontology-driven web-based interface. Cloudwave is currently used in the
      multicenter National Institute of Neurological Diseases and Stroke (NINDS)-funded
      Prevention and Risk Identification of SUDEP (sudden unexplained death in
      epilepsy) Mortality (PRISM) project to identify risk factors for sudden death in
      epilepsy. RESULTS: Comparative evaluations of Cloudwave with traditional desktop
      approaches to compute cardiac measures (eg, QRS complexes, RR intervals, and
      instantaneous heart rate) on epilepsy patient data show one order of magnitude
      improvement for single-channel ECG data and 20 times improvement for four-channel
      ECG data. This enables Cloudwave to support real-time user interaction with
      signal data, which is semantically annotated with a novel epilepsy and seizure
      ontology. DISCUSSION: Data privacy is a critical issue in using cloud
      infrastructure, and cloud platforms, such as Amazon Web Services, offer features
      to support Health Insurance Portability and Accountability Act standards.
      CONCLUSION: The Cloudwave platform is a new approach to leverage of large-scale
      electrophysiological data for advancing multicenter clinical research.

PMID- 24326540
TI  - Genes and immune response in alopecia areata: review of the alopecia areata
      research summit first day proceedings.

PMID- 24326541
TI  - Overview of alopecia areata.
AB  - Alopecia areata is a complex genetic, immune-mediated disease that targets anagen
      hair follicles. The disease affects children and adults and is characterized by
      round or oval patches of hair loss, loss of all scalp hair (alopecia totalis),
      body hair (alopecia universalis), or ophiasis pattern hair loss. Patients may
      also present with patchy loss in multiple hair-bearing areas. Commonly associated
      diseases include asthma, allergic rhinitis, atopic dermatitis, thyroid disease,
      and automimmune diseases, such as thyroiditis and vitiligo. Nail abnormalities
      may precede, follow, or occur concurrently with hair loss activity. Alopecia
      areata has no known age, race, or ethnic preponderance and in contrast to other
      autoimmune diseases such as thyroiditis or lupus, the hair follicle does not
      usually sustain permanent injury and maintains its potential to regrow hair. It
      is estimated that alopecia areata affects between six and seven million
      individuals in the United States. Genes, the immune and nervous systems have all
      been implicated in the pathogenesis of alopecia areata. Although many treatments
      are available, there is still no cure. Bolstered by new scientific and
      translational opportunities from recently published genome-wide association
      studies, an ambitious treatment development program has recently been initiated
      by the National Alopecia Areata Foundation. 

PMID- 24326542
TI  - The genetic architecture of alopecia areata.
AB  - A major impetus to initiating the Human Genome Project was the belief that
      information encoded in the human genome would "accelerate progress in
      understanding disease pathogenesis and in developing new approaches to diagnosis,
      treatment, and prevention in many areas of medicine". Alopecia areata (AA) is a
      notable example of how understanding the genetic basis of a disease can have an
      impact on the care of patients in a relatively short time. Our first genome-wide
      association study in AA identified an initial set of common variants that
      increase risk of AA, some of which are shared with other autoimmune diseases.
      Thus, there has already been rapid progress in the translation of this
      information into new therapeutic strategies for patients, as drugs are already on
      the market for some of these disorders that can now be tested in AA. Informed by
      the progress achieved with genetic studies for mechanistically aligned autoimmune
      diseases, we are poised to carry this work forward and interrogate the underlying
      disease mechanisms in AA. Importantly, future genetic studies aimed at
      identifying additional susceptibility genes will further establish the foundation
      for the application of precision medicine in the care of AA patients. 

PMID- 24326543
TI  - Alopecia areata: updates from the mouse perspective.
AB  - Alopecia areata (AA) is a cell-mediated autoimmune disease that targets actively
      growing hair follicles in mammals, including humans and mice. Development of the
      C3H/HeJ spontaneous mouse model AA nearly 20 years ago provided a much needed
      tool to test the hypotheses and ultimately serve as a preclinical model for drug
      testing. Discoveries in both human AA patients and the mouse model supported each
      other and lead to discoveries on the incredibly complex genetic basis of this
      disease. The discovery that A/J, MRL/MpJ, SJL/J, and SWR/J strains also develop
      AA now allows genome-wide association mapping studies to expand the list of genes
      underlying this disease. Potential new targets for unraveling the pathogenesis of
      AA include the role of retinoic acid metabolism in the severity of disease and
      hair shaft proteins that may be either the inciting antigen or ultimate target of
      the immune reaction leading to breakage of the shaft causing clinical alopecia.
      Comparing these model systems with human and mouse clinical disease, for both
      discovery and validation of the discoveries, continues to resolve the complex
      questions surrounding AA. 

PMID- 24326544
TI  - The role of hair follicle immune privilege collapse in alopecia areata: status
      and perspectives.
AB  - Alopecia areata (AA) may represent a CD8+T cell-mediated, organ-specific
      autoimmune disease in which as yet elusive autoantigens are recognized, once they
      become exposed by ectopic major histocompatibility complex class I expression by
      anagen hair follicles (HFs) that have lost their relative immune privilege (IP).
      On this basis, AA research is chiefly challenged with identifying the
      autoreactive CD8+T cells and their cognate autoantigens as well as key inducers
      of HF-IP collapse and "HF-IP guardians" that prevent and/or can restore IP
      collapse. However, natural killer group 2D-positive (NKG2D+) cells (incl. NK,
      NKT, and CD8+T cells) and NKG2D-activating ligands from the MICA (MHC I-related
      chain A) family may also have a key role in AA pathogenesis, as a massive
      infiltrate of IFN-gamma-secreting NKG2D+ cells alone suffices to induce the AA
      phenotype. Therefore, we speculate that AA may represent a stereotypic, but
      distinct HF response pattern to inflammatory insults associated with HF-IP
      collapse. 

PMID- 24326545
TI  - The biology of IL-15: implications for cancer therapy and the treatment of
      autoimmune disorders.
AB  - IL-15 has a pivotal role in life and death of natural killer (NK) and CD8 memory
      T cells. IL-15 signals through a heterotrimeric receptor involving the common
      gamma chain (gammac) shared with IL-2, IL-4, IL-7, IL-9, and IL-21, IL-2/IL-15
      receptor beta (IL-15Rbeta) shared with IL-2 and a private IL-15Ralpha subunit.
      IFN- or CD40 ligand-stimulated dendritic cells coordinately express IL-15 and IL
      15Ralpha. Cell surface IL-15Ralpha presents IL-15 in trans to cells that express
      IL-2/IL-15Rbeta and gammac. IL-15 is being used to treat patients with metastatic
      malignancy. However, IL-15 is an inflammatory cytokine involved in immunological
      memory including that to self, thereby playing a role in autoimmune diseases.
      These insights provide the scientific basis for clinical strategies directed
      toward diminishing IL-15 action. Dysregulated IL-15 expression was demonstrated
      in patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis,
      celiac disease, and alopecia areata. The monoclonal antibody Hu-Mik-beta-1
      targets the cytokine receptor subunit IL-2/IL-15Rbeta (CD122), blocks IL-15
      transpresentation, and is being used in clinical trials in patients with
      autoimmune diseases. In parallel, clinical trials have been initiated involving
      the Jak2/3 (Janus kinase-2/3) inhibitor tofacitinib and Jak1/2 inhibitor
      ruxolitinib to block IL-15 signaling. 

PMID- 24326546
TI  - Toward T cell protein-protein interaction activity relevant to alopecia areata.
AB  - Development of better therapies for the T cell-mediated autoimmune disease
      alopecia areata (AA) could be expedited by an improved understanding of the
      immunologic signals underlying its pathogenesis. To approach this, our group is
      mounting a new technological and analytical platform, multiplex
      immunoprecipitation detected by flow cytometry (MIF). MIF is designed to allow
      analysis of collections of protein-protein interactions that participate in T
      cell signaling webs. Early experiments suggest that MIF can detect the increased
      protein-protein interaction network activity that occurs under conditions of T
      cell antigenic stimulation. Future experiments will focus on application of MIF
      to T cells isolated from AA or control patient samples, to identify critical T
      cell signaling complexes associated with the disorder. 

PMID- 24326547
TI  - What can the genetics of psoriasis teach us about alopecia areata?
AB  - Previous genetic epidemiological studies of psoriasis and alopecia areata
      demonstrated strong heritability in first-degree relatives and in twins. In
      recent years, these two conditions have emerged as two skin diseases that are
      starting to yield their secrets through genome-wide association studies. Both
      diseases manifest prominent human leukocyte antigen (HLA) associations, psoriasis
      primarily with major histocompatibility complex (MHC) Class 1, specifically HLA
      Cw6, and alopecia areata primarily with MHC Class II. Despite these differences
      in HLA associations, both diseases have in common a prominent role for CD8+
      lymphocytes. The purpose of this brief review is to present the recent
      developments in the genetics of psoriasis. 

PMID- 24326548
TI  - A new humanized mouse model for alopecia areata.
AB  - Although alopecia areata (AA) is not life threatening, it may lead to severe
      psychological disturbances, reducing the quality of life in all ages. Thus, a new
      animal model is needed for shedding more light onto the pathogenesis of this cell
      mediated, organ-specific autoimmune disease to identify more effective
      therapeutic strategies. Recently, we succeeded in developing a new humanized
      mouse model of AA, which includes transplantation of healthy human scalp skin
      obtained from normal volunteers on to severe-combined immunodeficient mice. This
      is followed by intradermal injection of either autologous or allogeneic
      peripheral blood mononuclear cells, which had been cultured with high dose of IL
      2 and enriched for natural killer group 2D-positive (NKG2D+) and CD56+ cells.
      This protocol leads to rapid and predictable development of focal hair loss, with
      all the characteristic clinical, histological, and immunohistochemical features
      of AA. This humanized mouse AA model underscores the functional importance of
      NKG2D+ and CD56+ cells in AA pathogenesis and promises to be instrumental for
      identifying novel AA treatment strategies. 

PMID- 24326549
TI  - Pharmacogenomics in clinical drug development and potential for alopecia areata.
AB  - Alopecia areata, alopecia totalis, and alopecia universalis likely represent a
      constellation of related diseases with similar, yet distinct heritability
      markers. There is currently no known curative therapy that works universally for
      all patients. Pharmacogenomic research enables the pharmaceutical industry to
      understand variability of patient responses to drugs during clinical drug
      development and during post-marketing surveillance. Understanding the genetic
      basis for patient response/non-response can enable the development of
      individualized therapies for those patients with an inherited basis for altered
      response to drug therapy. There are multiple examples of drugs that now contain a
      recommendation for genetic testing before dosing in their drug labels, directing
      clinicians to obtain genetic information for each individual patient in order to
      help direct drug therapy. 

PMID- 24326550
TI  - Alopecia areata and its effects on patients.
AB  - The onset of alopecia areata creates a roller coaster of emotions. Like the
      disease, a patient's emotions are unpredictable. The lack of control over one's
      body is both frightening and intimidating. Alopecia areata not only impacts an
      individual but it also has a halo effect, impacting family and friends, thereby
      increasing the number of people affected by the disease. 

PMID- 24326551
TI  - Current treatment of alopecia areata.
AB  - Treatment of alopecia areata is dependent on age of patient as well as the extent
      and duration of scalp involvement. Treatments include steroids, topical
      immunotherapy, topical minoxidil, anthralin, and immunosuppressants. Each case
      must be dealt with on a customized individual basis. 

PMID- 24326552
TI  - DNCB use in treating extensive alopecia areata.
AB  - The author has been treating extensive cases of alopecia areata with 1-chloro-2,
      4-dinitrobenzene (DNCB) for 35 years with considerable success. This presentation
      outlines the protocol that has been used. 

PMID- 24326553
TI  - Treatment development program: the National Alopecia Areata Foundation's
      initiative for achieving safe and effective therapies.
AB  - Founded in 1981, the National Alopecia Areata Foundation (NAAF) is dedicated to
      research to find a cure or acceptable treatment for alopecia areata (AA), to
      develop support for people affected by the disease, and to educate the public
      about it. NAAF has developed into an international organization advancing patient
      interests in a number of ways. Beginning in 2008, NAAF organized a series of
      research summits that focused AA research investments into genetic, molecular,
      and immunological investigations as well as laying the groundwork for clinical
      trials and support for regulatory evaluation of prospectively available
      treatments. This multifaceted initiative is called the Alopecia Areata Treatment
      Development Program (TDP). It is representative of initiatives among voluntary
      patient advocacy organizations to partner with academic, clinical, government,
      and biotechnology interests to accelerate the development and approval of
      treatments for understudied diseases. The article describes key steps in the
      development of TDP, its progress, and future direction. 

PMID- 24326554
TI  - Universal protocol for alopecia areata clinical studies.
AB  - Within the area of alopecia areata research, there is an obvious need for well
      designed clinical trials of therapeutic agents. The National Alopecia Areata
      Foundation (NAAF) has created an initiative for the development of a unified
      protocol with guidelines for clinical studies. The NAAF universal protocol
      represents a joint effort of clinicians and investigators with experience in
      treating alopecia areata. This protocol will serve as a tremendous resource to
      facilitate future clinical studies. 

PMID- 24326555
TI  - Health-Related Quality of Life (HRQoL) in alopecia areata patients-a secondary
      analysis of the National Alopecia Areata Registry Data.
AB  - Alopecia areata (AA) is a nonscarring and recurrent disease characterized by hair
      loss that may significantly affect patient health-related quality of life
      (HRQoL). Given the lack of reliable and accurate reporting of HRQoL status in
      patients with AA, we analyzed data from 532 AA patients from the National
      Alopecia Areata Registry whose registry record included HRQoL assessments using
      three validated instruments: Skindex-16, brief version of the Fear of Negative
      Evaluation Scale, and Dermatology Life Quality Index. The mean HRQoL scores were
      compared with previously reported HRQoL levels from healthy controls and patients
      with other skin diseases. Two-step cluster analysis of Skindex-16 scales divided
      patients into two groups: 481 (57%) with good HRQoL and 361 (43%) with poor
      HRQoL. Multivariate logistic regression modeling revealed a set of risk factors
      for poor HRQoL: age <50 years (odds ratio (OR) 3.99, 95% confidence interval (CI)
      1.66-9.58), female gender (OR 2.74, 95% CI 1.73-4.34), hair loss 25-99% (OR 2.47,
      95% CI 1.12-5.45), family stress (OR 1.8, 95% CI 1.13-2.86), and job change (OR
      2.01, 95% CI 1.02-3.94). The current analysis provides an overview of the HRQoL
      status of AA patients and may guide patient care in the future. 

PMID- 24326556
TI  - Summary of the preceding three alopecia areata research summits: what's past is
      prologue.

PMID- 24326557
TI  - Development of the alopecia areata symptom impact scale.
AB  - The existing literature on alopecia areata (AA) clearly demonstrates patients'
      concerns related to physical symptoms, emotional well-being, mental health,
      social functioning, and other dimensions of daily functioning. Although
      questionnaires such as the Skindex-16 and the Dermatology Life Quality Index have
      been used, these questionnaires were validated for skin conditions other than AA
      as a chronic condition. The goals of this study are to develop a measure of
      quality of life, symptoms, and their impact for patients with AA called the
      Alopecia Areata Symptom Impact Scale (AASIS) and to provide psychometric evidence
      for its use. We used data from 1,400 patients from the National Alopecia Areata
      Registry together with clinical experts' reviews and quantitative approaches. The
      preliminary version of the AASIS with 13 items was administered to about 210
      patients with AA. Results indicated that the AASIS measures three underlying
      constructs related to AA. These dimensions were impact of AA, hair loss, and
      physical skin symptoms. The internal consistency reliabilities of these subscales
      are 0.93, 0.86, and 0.81, respectively. Cognitive debriefing results showed that
      patients find the AASIS items easy to understand, clear, and concise. Preliminary
      evidence suggests that the AASIS is a reliable and valid measure of the symptoms
      and their impact in patients with AA. 

PMID- 24326558
TI  - The national alopecia areata registry-update.

PMID- 24326559
TI  - Growth hormone deficiency in a young patient with alopecia areata.
AB  - A young female child aged 7 years presented initially with chronic alopecia
      areata, which over 2 years progressed to alopecia areata universalis. 

PMID- 24326560
TI  - Association between alopecia areata, psoriasis vulgaris, thyroid disease, and
      metabolic syndrome.
AB  - Although the association between alopecia areata (AA), psoriasis, and other
      autoimmune diseases has been well reported in the literature, an association with
      metabolic syndrome has not been reported. We present two young women with the
      combination of severe psoriasis, androgen excess, metabolic syndrome,
      thyroiditis, and AA. Both women ultimately progressed to treatment-resistant
      alopecia universalis. This constellation of autoimmunity and metabolic syndrome
      presents a therapeutic challenge while highlighting the need for full laboratory
      assessment of AA patients. Careful selection of biological treatment regimens may
      offer therapeutic benefit for both their psoriasis and AA while giving us
      experience with the newer biologics in AA. 

PMID- 24326561
TI  - Clinical response to combined therapy of cyclosporine and prednisone.
AB  - Reported is a patient with severe alopecia areata, multiple autoimmune diseases
      (chronic lymphocytic thyroidis, primary ovarian failure), and Down syndrome. She
      had a poor response to topical treatment with glucocorticoids and minoxidil, but
      showed some improvement with glucocorticoid injections. At the time of
      evaluation, she had hair loss on 85-90% of her scalp. She was treated initially
      with oral prednisone 50 mg per day for 2 weeks, followed by a 3-month course of
      prednisone 10 mg per day and cyclosporine 125 mg (4 mg kg(-1)) two times per day.
      She responded well with excellent regrowth of hair on the scalp, and prednisone
      was tapered and ultimately discontinued. Importantly, her parents noted marked
      improvement in sense of well-being. Several months after discontinuing treatment,
      she developed hyperpigmentation on the trunk consistent with confluent and
      reticulated papillomatosis; she has several known risk factors for this disorder,
      but it is not clear if this is related to her previous treatment. 

PMID- 24326562
TI  - Hepatitis C treatment and alopecia totalis.
AB  - Peg-interferon alpha-2a and 2b and ribavirin have become the mainstays of chronic
      hepatitis C treatment. Although various cutaneous side effects have been
      reported, alopecia areata in its various forms have rare reports and has not been
      well categorized. Here we present a case of alopecia universalis occurring
      shortly after treatment for chronic hepatitis C, and we discuss some of the
      implications this has in understanding the pathophysiology of alopecia areata. 

PMID- 24326563
TI  - Therapy for alopecia areata in mice using parathyroid hormone agonists and
      antagonists, linked to a collagen-binding domain.
AB  - Alopecia areata is a common form of hair loss in which autoimmune-mediated
      destruction of hair follicles causes patchy hair loss, for which there is no
      adequate therapy. Parathyroid hormone (PTH) induces the hair cycle and promotes
      hair growth. PTH-CBD is a fusion protein of PTH and a bacterial collagen-binding
      domain (CBD), leading to targeted delivery to and retention in the skin collagen.
      We tested the effects of a single dose of PTH-CBD (low or high dose) on an animal
      model for alopecia areata, the C3H/HeJ engrafted mouse. In all the treated
      animals, there was a rapid (1-4 days) increase in hair growth, with sustained
      effects observed over a 2-month period (7/10 total treated mice<40% hair loss
      based on gray scale analysis, vs. 2/5 in vehicle control animals). Histological
      examination revealed massive stimulation of anagen VI hair follicles in treated
      animals despite an ongoing immune response. PTH-CBD thus shows promise as a
      therapy for alopecia areata, likely in conjunction with a mild immune
      suppressant, such as hydrocortisone cream. 

PMID- 24326564
TI  - What looks like alopecia areata is not always alopecia areata.
AB  - The differential diagnosis of a strongly positive and painless hair pull test
      includes alopecia areata and loose anagen syndrome. A hair mount examined with
      low power light microscopy easily clarifies the diagnosis. 

PMID- 24326565
TI  - A single question can make the diagnosis.
AB  - Alopecia areata is the only condition that can cause complete hair loss in 3
      months without symptoms or signs. 

PMID- 24326566
TI  - Cutaneous drug delivery: an update.
AB  - Cutaneous delivery of therapeutics represents a proven and attractive option for
      treating a variety of dermatologic conditions with minimal systemic side effects.
      Although there have been many innovations in drug delivery systems, the number of
      effective cutaneous drugs remains small, primarily because of the stratum corneum
      permeability barrier. Overcoming this barrier safely and reversibly to deliver
      large hydrophilic drugs cutaneously is one of the major challenges in the field
      of dermatologic therapy. 

PMID- 24326567
TI  - Janus kinases: an ideal target for the treatment of autoimmune diseases.
AB  - Cytokines have pivotal roles in the maintenance of an appropriate immune
      response. Targeting cytokine receptors has been an effective means of treating
      immune-related disorders. In the past few years, research efforts have been
      directed toward cytokines' intracellular signaling pathways and, in particular,
      the JAK-STAT (Janus kinase-signal transducers and activation of transcription)
      signaling cascade. Recently, spearheaded by the development of effective drugs in
      cancer treatment, it has become clear that the targeting of intracellular protein
      kinases is a very attractive and feasible possibility for the treatment of
      autoimmune disorders. The targeting of the Janus kinases (JAKs) has been quite
      successful and two JAK inhibitors are now approved to be used in humans.
      Interestingly, although some of the inhibitors developed and tested to date have
      been shown to target more than one kinase, this promiscuity does not appear to be
      problematic. Novel second-generation, more specific inhibitors are under
      development, and in the next few years, we expect this class of drugs to become a
      powerful tool in the hands of clinician treating autoimmune diseases. 

PMID- 24326568
TI  - Safety and efficacy of bimatoprost solution 0.03% topical application in patients
      with chemotherapy-induced eyelash loss.
AB  - Few dermatologic conditions carry as much anxiety and emotional distress as hair
      loss resulting from a disease condition such as alopecia areata or as a result of
      cytotoxic drug treatment, e.g., after chemotherapy. Bimatoprost 0.03% solution is
      a Food and Drug Administration-approved prescription product indicated for the
      treatment of eyelash hypotrichosis. The product was investigated in a double
      masked, randomized, and placebo-controlled study in patients who had significant
      eyelash loss or hypotrichosis as a result of chemotherapy. Once-daily treatment
      with bimatoprost ophthalmic solution 0.03% to the upper eyelid margin restored
      eyelash growth and prominence more quickly than the slower, natural course of
      recovery observed in the vehicle control subjects. The eyelash prominence
      measured using a validated Global Eyelash Assessment (GEA) scale demonstrated a
      statistically significant increase over placebo following 6 months of treatment.
      Efficacy was also demonstrated using a validated objective digital image analysis
      methodology to show significant increase in eyelash length, thickness/fullness,
      and darkness in these patients. Bimatoprost was found to be well tolerated over
      the 1-year treatment period. 

PMID- 24326569
TI  - Excimer laser: a module of the alopecia areata common protocol.
AB  - Alopecia areata (AA) is an autoimmune condition characterized by T cell-mediated
      attack of the hair follicle. The inciting antigenic stimulus is unknown. A dense
      perbulbar lymphocytic infiltrate and reproducible immunologic abnormalities are
      hallmark features of the condition. The cellular infiltrate primarily consists of
      activated T lymphocytes and antigen-presenting Langerhans cells. The xenon
      chloride excimer laser emits its total energy at the wavelength of 308 nm and
      therefore is regarded as a "super-narrowband" UVB light source. Excimer laser
      treatment is highly effective in psoriasis, another T cell-mediated disorder that
      shares many immunologic features with AA. The excimer laser is superior in
      inducing T cell apoptosis in vitro compared with narrowband UVB, with paralleled
      improved clinical efficacy. The excimer laser has been used successfully in
      patients with AA. In this context, evaluation of the potential benefit of 308-nm
      excimer laser therapy in the treatment of AA is clinically warranted. Herein, the
      use of a common treatment protocol with a specifically designed module to study
      the outcome of excimer laser treatment on moderate-to-severe scalp AA in adults
      is described. 

PMID- 24326574
TI  - Sulfur-amine chemistry-based synthesis of multi-walled carbon nanotube-sulfur
      composites for high performance Li-S batteries.
AB  - We report a sulfur-amine chemistry-based method to prepare multi-walled carbon
      nanotube-sulfur (MWNT-S) composites in a highly efficient and quantitative
      manner. The resulting MWNT-S composites exhibit excellent cycling stability at up
      to 400 cycles, with high sulfur loading. Developing this method also increases
      the number of research routes that could be pursued with respect to Li-S
      batteries. 

PMID- 24326576
TI  - Self-testing for HIV and its impact on public health.

PMID- 24326577
TI  - Risk factors for congenital syphilis and adverse pregnancy outcomes in offspring
      of women with syphilis in Shenzhen, China: a prospective nested case-control
      study.
AB  - BACKGROUND: Despite existence of a highly effective intervention, maternal
      syphilis still causes substantial perinatal morbidity and mortality, even in
      China, where antenatal health services are strong. This study sought to address
      personal, programmatic, and other risk factors for congenital syphilis (CS) and
      adverse pregnancy outcomes (APOs) among pregnant women in Shenzhen, China.
      METHODS: Pregnant women attending antenatal services were offered serologic
      tests, and those diagnosed as having syphilis were recruited from April 2007 to
      October 2012. In a nested case-control study for the pregnancy outcomes of
      syphilis-infected women, we assessed risk factors comparing infants born with CS
      (group II) and with any APOs (group III) to infants without CS or APOs (group I).
      RESULTS: During the 66-month study period, we screened 279,334 pregnant women and
      identified 838 (0.3%; 95% confidence interval, 0.28%-0.32%) women infected with
      syphilis. Among infants born to syphilitic mothers, 8.2% (34/417) were diagnosed
      as having CS and 24.7% (103/417) were diagnosed as having APOs. Compared with
      group I, maternal baseline titers of nontreponemal antibodies (adjusted odds
      ratio [aOR], 2.13), stage of syphilis (aOR, 21.56), length of time between the
      end of the first treatment to childbirth (aOR, 11.93), gestational week at
      treatment (aOR, 2.63), and fathers' cocaine use (aOR, 15.44) and syphilis
      infection status (aORpositive vs. negative, 5.84; aORunknown vs. negative, 5.55)
      were positively associated with CS, but prenatal care (aOR, 0.11) and complete
      treatment (aOR, 0.20) were negatively associated with CS. Maternal age (aOR,
      1.43), marriage (aOR, 2.41), history of cocaine use (aOR, 3.79) and ectopic
      pregnancy (aOR, 5.91), baseline titers of nontreponemal antibodies (aOR, 1.30),
      stage of syphilis (aOR, 8.89), length of time between the end of the first
      treatment to childbirth (aOR, 2.52), gestational week at treatment (aOR, 1.78),
      and fathers' syphilis infection status (aORunknown vs. negative, 2.02) were also
      positively associated with APOs, but maternal history of syphilis (aOR, 0.44),
      prenatal care (aOR, 0.29), and complete treatment (aOR, 0.25) were negatively
      associated with APOs, CONCLUSIONS: Syphilis was an important cause of pregnancy
      loss and infant disability, particularly among women who did not receive prenatal
      care or had late or inadequate treatment. These study results can inform
      antenatal programs on the importance of early syphilis testing and prompt and
      appropriate treatment. Some strategies targeted at other risk factors areas may
      be helpful.

PMID- 24326578
TI  - Improved reverse screening algorithm for Treponema pallidum antibody using signal
      to-cutoff ratios from chemiluminescence microparticle immunoassay.
AB  - BACKGROUND: The widespread reverse syphilis screening algorithm involves 1 more
      treponemal test than the traditional screening algorithm, resulting in increased
      medical costs. In the first screening step of the algorithm, a chemiluminescence
      microparticle immunoassay is used to detect Treponema pallidum (TP) antibody on
      the basis of signal-to-cutoff (S/CO) ratios. We hypothesized that by analyzing
      S/CO ratios, we could determine a strategy to reduce unnecessary confirmatory
      testing. METHODS: The ARCHITECT Syphilis TP assay using the chemiluminescence
      microparticle immunoassay was used as a syphilis screening test, and all reactive
      results were followed up with a toluidine red unheated serum test (TRUST) and a
      TP particle agglutination (TPPA) assay. We evaluated the S/CO ratios of 319
      reactive samples of a total of 8980 that were included in the screening tests. A
      receiver operating characteristic curve was used to determine the optimal S/CO
      ratio to predict confirmatory TPPA results. RESULTS: When the S/CO ratio was 9.9
      or greater, the specificity and positive predictive value were both determined to
      be 100.0%. All samples (194/194) with S/CO ratios of 9.9 or greater, even with
      negative results for TRUST, were confirmed to be positive for treponemal
      antibody. CONCLUSIONS: A sample with an S/CO ratio of 9.9 or greater in initial
      screening does not need an extra confirmatory TPPA test, although the sample has
      a negative result for TRUST. We propose a potentially cost-effective reverse
      screening algorithm, obviating the need for the secondary treponemal testing in
      65.2% of the screening-reactive samples.

PMID- 24326579
TI  - Migration distorts surveillance estimates of engagement in care: results of
      public health investigations of persons who appear to be out of HIV care.
AB  - BACKGROUND: Prevention and clinical efforts are increasingly focused on improving
      the HIV care cascade, the sequential steps from diagnosis to engagement in care
      and viral suppression. Monitoring of this cascade is largely dependent on HIV
      laboratory surveillance data. However, little is known about the completeness of
      these data or the true care status of individuals for whom no data are reported.
      METHODS: We investigated people presumed to be living with HIV/AIDS in King
      County, WA, who had no laboratory results reported to HIV surveillance for at
      least 1 year between 2006 and 2010. We determined whether each person had
      relocated, died, or remained in the county. RESULTS: Of 7379 HIV-infected people
      presumed living in King County, 2545 (35%) had 1 or more 12-month gap in
      laboratory reporting. Among these individuals, 47% had relocated, 7% died, and
      38% remained in King County; we were unable to determine the status of 8%. Of
      individuals remaining in the area, 91% had evidence of returning to or being in
      HIV care. Case investigations reduced the proportion of individuals thought to be
      out of care in 2011 from 27% to 16%. CONCLUSIONS: Investigations of individuals
      without laboratory results reported to HIV surveillance identified large numbers
      of people who are no longer living in the area. Our findings suggest that current
      estimates of the HIV care cascade may be too pessimistic and that individual case
      investigations are required to accurately define the size and composition of the
      population of people living with HIV in local areas.

PMID- 24326580
TI  - The HIV care cascade: simple concept, complex realization.

PMID- 24326581
TI  - Potential impact and acceptability of Internet partner notification for men who
      have sex with men and transgender women recently diagnosed as having sexually
      transmitted disease in Lima, Peru.
AB  - We assessed the potential impact of Internet partner notification among men who
      have sex with men and transgender women in Peru recently diagnosed as having
      sexually transmitted disease. Use of Internet partner notification was
      anticipated for 55.9% of recent partners, including 43.0% of partners not
      currently expected to be notified, a 20.6% increase in anticipated notification
      outcomes. 

PMID- 24326583
TI  - Check Yourself: a social marketing campaign to increase syphilis screening in Los
      Angeles County.
AB  - BACKGROUND: In 2007, the Los Angeles County Department of Public Health launched
      Check Yourself, a new social marketing campaign, as part of ongoing efforts to
      address the persistent syphilis epidemic among men who have sex with men (MSM) in
      the county. The goals of the campaign were to increase syphilis testing and
      knowledge among MSM. Check Yourself was planned with careful attention to the
      principles of social marketing, including formative research, market
      segmentation, and an emphasis on building a strong brand. METHODS: A cross
      sectional survey using a time-location sample was conducted in 2009 for the
      evaluation. The survey assessed demographics, syphilis knowledge, and recent
      syphilis testing as well as unaided awareness, aided awareness, and confirmed
      awareness, meaning that a person had both awareness of the campaign and could
      correctly identify that the campaign was about syphilis. The total sample size
      was 306. RESULTS: Unaided awareness for Check Yourself was 20.7%, and aided
      awareness was 67.5%, bringing total campaign awareness to 88.2%; confirmed
      awareness was 30.4%. Unaided campaign awareness was associated with syphilis
      knowledge and important risk behaviors for syphilis, indicating that the campaign
      reached an appropriate audience. Total awareness was not associated with recent
      syphilis testing in a multivariate model. However, MSM with confirmed awareness
      were more than 6 times more likely to have been recently tested. CONCLUSIONS: The
      evaluation of Check Yourself found that the campaign had a very strong brand
      among MSM. Although total awareness was not associated with syphilis testing,
      confirmed awareness, a more robust measure, was strongly associated.

PMID- 24326582
TI  - Would young women attending sexually transmitted disease clinics benefit from
      human papillomavirus vaccination? An assessment of human papillomavirus DNA and
      seropositivity from human papillomavirus sentinel surveillance, 2003-2005.
AB  - BACKGROUND: There are limited data on the proportion who have been exposed to
      vaccine-type human papillomavirus (HPV) among women attending sexually
      transmitted disease (STD) clinics; this information could inform the potential
      benefits of HPV vaccination for women attending this venue. METHODS: Human
      papillomavirus surveillance was conducted in STD clinics in Baltimore, MD;
      Boston, MA; Denver, CO; Los Angeles, CA; and Seattle, WA, among women receiving
      cervical cancer screening from January 2003 to December 2005. The women had
      specimens collected for cervical cytology HPV testing by L1 consensus polymerase
      chain reaction testing and serologic assessment for HPV 6, 11, 16, and 18 using
      the competitive Luminex immunoassay. Results from 880 women with adequate
      specimens were included. Women were HPV naive if they were both HPV DNA negative
      and seronegative for a specific HPV type. RESULTS: One hundred seventy women
      (19.3%) had HPV 16, 18, 6, or 11 DNA, and 418 (47.5%) were HPV 16, 18, 6, or 11
      seropositive. Four hundred ten (46.6%) women were naive to all 4 types, 570
      (64.8%) were naive to both HPV 16 and 18, and 545 (61.9%) were naive to both HPV
      6 and 11. Almost all (99.3%) women were naive to at least 1 vaccine HPV type.
      CONCLUSIONS: Almost half of young women age eligible for HPV vaccine and
      attending STD clinics were naive to all 4 HPV types, and more than half were
      naive to both HPV 16 and 18. This assessment suggests that most young women
      attending this venue might benefit from HPV vaccination.

PMID- 24326584
TI  - A comparison of Internet search trends and sexually transmitted infection rates
      using Google trends.
AB  - Google Trends was used to determine the relationship between sexually transmitted
      infection (STI)-related search engine trends and STI rates. Trends seem to be
      similar to the relative rates of STIs and to regional differences in rates.
      Search engine trends are an innovative tool to integrate into STI surveillance. 

PMID- 24326585
TI  - Chlamydia and gonorrhea diagnosis, treatment, personnel cost savings, and service
      delivery improvements after the implementation of express sexually transmitted
      disease testing in Maricopa County, Arizona.
AB  - BACKGROUND: The demand for low-cost sexually transmitted disease (STD) services
      in Maricopa County (Phoenix area) is high. Improved methods for STD/HIV testing
      are needed to increase the number of patients receiving testing. OBJECTIVES: The
      present study sought to evaluate an STD/HIV express testing (ET) option for
      patients identified as being at lower risk for infection. METHODS: Clients
      reporting current STD symptoms, contact to an infected partner, or health
      department referral were identified via questionnaire and routed to a traditional
      provider visit (PV); those not reporting these situations were routed to ET
      (laboratory-only). Demographics, treatment completion, and treatment intervals
      were compared among patients diagnosed as having chlamydia and gonorrhea through
      ET and PV encounters in September 2008 to July 2011. Personnel costs were
      compared for each of the 2 visit types. The number of clinic turn-aways for the 2
      month time interval before the start of the program was compared with the 2-month
      interval at the end of the evaluation. RESULTS: Of the 36,946 clients seen at
      Maricopa County Department of Public Health, 7466 (20.2%) were patients seen
      through express visits. Overall chlamydia and gonorrhea positivity was lower
      among ET patients (527/7466; 7.1%) as compared with those tested through PVs
      (6323/29,480; 21.4%). Treatment completion rates were comparable but were higher
      among patients seen through PVs (99%) as compared with ET (94%). A savings of
      $2936 per 1000 patients seen was achieved when 20% of clients were routed through
      ET. Clinic turn-aways decreased significantly, from 159 clients during the 2
      months before implementation of ET to 6 patients during the last 2 months of
      evaluation (96% reduction). CONCLUSIONS: This ET system included an effective
      patient routing process that provided an efficient way to increase access to STD
      testing among persons at lower risk, at a reduced cost per patient, while
      maintaining high treatment coverage.

PMID- 24326586
TI  - Echocardiographic assessment of the right heart in mice.
AB  - Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely
      used to study the pathophysiology of PAH and to investigate potential therapies.
      Given the expense and time involved in creating animal models of disease, it is
      critical that researchers have tools to accurately assess phenotypic expression
      of disease. Right ventricular dysfunction is the major manifestation of pulmonary
      hypertension. Echocardiography is the mainstay of the noninvasive assessment of
      right ventricular function in rodent models and has the advantage of clear
      translation to humans in whom the same tool is used. Published echocardiography
      protocols in murine models of PAH are lacking. In this article, we describe a
      protocol for assessing RV and pulmonary vascular function in a mouse model of PAH
      with a dominant negative BMPRII mutation; however, this protocol is applicable to
      any diseases affecting the pulmonary vasculature or right heart. We provide a
      detailed description of animal preparation, image acquisition and hemodynamic
      calculation of stroke volume, cardiac output and an estimate of pulmonary artery
      pressure. 

PMID- 24326587
TI  - X-linked congenital ptosis and associated intellectual disability, short stature,
      microcephaly, cleft palate, digital and genital abnormalities define novel
      Xq25q26 duplication syndrome.
AB  - Submicroscopic duplications along the long arm of the X-chromosome with known
      phenotypic consequences are relatively rare events. The clinical features
      resulting from such duplications are various, though they often include
      intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and
      feeding difficulties. Female carriers are often phenotypically normal or show a
      similar but milder phenotype, as in most cases the X-chromosome harbouring the
      duplication is subject to inactivation. Xq28, which includes MECP2 is the major
      locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25
      and Xq26 have been reported in only a few cases. Using genome-wide array
      platforms we identified overlapping interstitial Xq25q26 duplications ranging
      from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males
      and seven affected females. All affected males shared a common phenotype with
      intrauterine- and postnatal growth retardation and feeding difficulties in
      childhood. Three had microcephaly and two out of five suffered from epilepsy. In
      addition, three males had a distinct facial appearance with congenital bilateral
      ptosis and large protruding ears and two of them showed a cleft palate. The
      affected females had various clinical symptoms similar to that of the males with
      congenital bilateral ptosis in three families as most remarkable feature.
      Comparison of the gene content of the individual duplications with the respective
      phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A,
      GPC3 and IGSF1) for the common phenotypes, including candidate loci for
      congenital bilateral ptosis, small head circumference, short stature, genital and
      digital defects. 

PMID- 24326588
TI  - ABA-insensitive3, ABA-insensitive5, and DELLAs Interact to activate the
      expression of SOMNUS and other high-temperature-inducible genes in imbibed seeds
      in Arabidopsis.
AB  - Seeds monitor the environment to germinate at the proper time, but different
      species respond differently to environmental conditions, particularly light and
      temperature. In Arabidopsis thaliana, light promotes germination but high
      temperature suppresses germination. We previously reported that light promotes
      germination by repressing SOMNUS (SOM). Here, we examined whether high
      temperature also regulates germination through SOM and found that high
      temperature activates SOM expression. Consistent with this, som mutants
      germinated more frequently than the wild type at high temperature. The induction
      of SOM mRNA at high temperature required abscisic acid (ABA) and gibberellic acid
      biosynthesis, and ABA-insensitive3 (ABI3), ABI5, and DELLAs positively regulated
      SOM expression. Chromatin immunoprecipitation assays indicated that ABI3, ABI5,
      and DELLAs all target the SOM promoter. At the protein level, ABI3, ABI5, and
      DELLAs all interact with each other, suggesting that they form a complex on the
      SOM promoter to activate SOM expression at high temperature. We found that high
      temperature-inducible genes frequently have RY motifs and ABA-responsive elements
      in their promoters, some of which are targeted by ABI3, ABI5, and DELLAs in vivo.
      Taken together, our data indicate that ABI3, ABI5, and DELLAs mediate high
      temperature signaling to activate the expression of SOM and other high
      temperature-inducible genes, thereby inhibiting seed germination.

PMID- 24326589
TI  - Phosphatidylinositol 4,5-bisphosphate influences PIN polarization by controlling
      clathrin-mediated membrane trafficking in Arabidopsis.
AB  - The functions of the minor phospholipid phosphatidylinositol-4,5-bisphosphate
      [PtdIns(4,5)P2] during vegetative plant growth remain obscure. Here, we targeted
      two related phosphatidylinositol 4-phosphate 5-kinases (PI4P 5-kinases) PIP5K1
      and PIP5K2, which are expressed ubiquitously in Arabidopsis thaliana. A pip5k1
      pip5k2 double mutant with reduced PtdIns(4,5)P2 levels showed dwarf stature and
      phenotypes suggesting defects in auxin distribution. The roots of the pip5k1
      pip5k2 double mutant had normal auxin levels but reduced auxin transport and
      altered distribution. Fluorescence-tagged auxin efflux carriers PIN-FORMED (PIN1)
      green fluorescent protein (GFP) and PIN2-GFP displayed abnormal, partially apolar
      distribution. Furthermore, fewer brefeldin A-induced endosomal bodies decorated
      by PIN1-GFP or PIN2-GFP formed in pip5k1 pip5k2 mutants. Inducible overexpressor
      lines for PIP5K1 or PIP5K2 also exhibited phenotypes indicating misregulation of
      auxin-dependent processes, and immunolocalization showed reduced membrane
      association of PIN1 and PIN2. PIN cycling and polarization require clathrin
      mediated endocytosis and labeled clathrin light chain also displayed altered
      localization patterns in the pip5k1 pip5k2 double mutant, consistent with a role
      for PtdIns(4,5)P2 in the regulation of clathrin-mediated endocytosis. Further
      biochemical tests on subcellular fractions enriched for clathrin-coated vesicles
      (CCVs) indicated that pip5k1 and pip5k2 mutants have reduced CCV-associated PI4P
      5-kinase activity. Together, the data indicate an important role for
      PtdIns(4,5)P2 in the control of clathrin dynamics and in auxin distribution in
      Arabidopsis. 

PMID- 24326591
TI  - Protective effect of esculin against prooxidant aflatoxin B1-induced
      nephrotoxicity in mice.
AB  - The study was designed to investigate the protective effect of esculin against
      pro-oxidant aflatoxin B1 (AFB1)-induced nephrotoxicity in mice. In this study
      toxicity was developed by oral administration of AFB1 at a dose of 66.60 MUg/kg
      bw/day for 90 days in male Swiss albino mice. Esculin (150 mg/kg bw/0.2 ml/day)
      and standard compound ascorbic acid (300 mg/kg bw/0.2 ml/day) was given after 30
      min of AFB1 administration for 90 days. Protective efficacy was assessed by
      measuring the levels of lipid peroxidation (LPO) and non-enzymatic antioxidants
      such as reduced glutathione (GSH) and also by measuring activities of enzymatic
      antioxidants such as glutathione peroxidase (GPX), glutathione-S-transferase
      (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT)
      in kidney. Results were analysed at the 30(th), 60(th) and 90(th) day of the
      daily treatments, which showed a decrease in the level of LPO and an increase in
      the levels of enzymatic and non-enzymatic antioxidants. The protective effect of
      esculin was further proved by histopathological findings as it exhibited
      regenerative activities in mice renal tubules against AFB1-induced
      nephrotoxicity. The results obtained clearly demonstrate that the protective
      efficacy of esculin against pro-oxidant AFB1-induced nephrotoxicity in mice might
      be due to its antioxidants and free radical scavenging properties. 

PMID- 24326590
TI  - Arabidopsis ERG28 tethers the sterol C4-demethylation complex to prevent
      accumulation of a biosynthetic intermediate that interferes with polar auxin
      transport.
AB  - Sterols are vital for cellular functions and eukaryotic development because of
      their essential role as membrane constituents. Sterol biosynthetic intermediates
      (SBIs) represent a potential reservoir of signaling molecules in mammals and
      fungi, but little is known about their functions in plants. SBIs are derived from
      the sterol C4-demethylation enzyme complex that is tethered to the membrane by
      Ergosterol biosynthetic protein28 (ERG28). Here, using nonlethal loss-of-function
      strategies focused on Arabidopsis thaliana ERG28, we found that the previously
      undetected SBI 4-carboxy-4-methyl-24-methylenecycloartanol (CMMC) inhibits polar
      auxin transport (PAT), a key mechanism by which the phytohormone auxin regulates
      several aspects of plant growth, including development and responses to
      environmental factors. The induced accumulation of CMMC in Arabidopsis erg28
      plants was associated with diagnostic hallmarks of altered PAT, including the
      differentiation of pin-like inflorescence, loss of apical dominance, leaf fusion,
      and reduced root growth. PAT inhibition by CMMC occurs in a brassinosteroid
      independent manner. The data presented show that ERG28 is required for PAT in
      plants. Furthermore, it is accumulation of an atypical SBI that may act to
      negatively regulate PAT in plants. Hence, the sterol pathway offers further
      prospects for mining new target molecules that could regulate plant development. 

PMID- 24326592
TI  - Editorial comment: Symposium: 2013 Hip Society proceedings.

PMID- 24326593
TI  - Deltoid-split or deltopectoral approaches for the treatment of displaced proximal
      humeral fractures?
AB  - BACKGROUND: Proximal humeral fractures are mainly associated with osteoporosis
      and are becoming more common with the aging of our society. The best surgical
      approach for internal fixation of displaced proximal humeral fractures is still
      being debated. QUESTIONS/PURPOSES: In this prospective randomized study, we aimed
      to investigate whether the deltoid-split approach is superior to the
      deltopectoral approach with regard to (1) complication rate; (2) shoulder
      function (Constant score); and (3) pain (visual analog scale [VAS]) for internal
      fixation of displaced humeral fractures with a polyaxial locking plate. METHODS:
      We randomized 120 patients with proximal humeral fractures to receive one of
      these two approaches (60 patients for each approach). We prospectively documented
      demographic and perioperative data (sex, age, fracture type, hospital stay,
      operation time, and fluoroscopy time) as well as complications. Followup
      examinations were conducted at 6 weeks, 6 months, and 12 months postoperatively,
      including radiological and clinical evaluations (Constant score, activities of
      daily living, and pain [VAS]). Baseline and perioperative data were comparable
      for both approaches. The sample size was chosen to provide 80% power, but it
      reached only 68% as a result of the loss of followups to detect a 10-point
      difference on the Constant score, which we considered the minimum clinically
      important difference. RESULTS: Complications or reoperations between the
      approaches were not different. Eight patients in the deltoid-split group (14%)
      needed surgical revisions compared with seven patients in the deltopectoral group
      (13%; p = 1.00). Deltoid-split and deltopectoral approaches showed similar
      Constant scores 12 months postoperatively (Deltoid-split 81; 95% confidence
      interval [CI], 74-87 versus deltopectoral 73; 95% CI, 64-81; p = 0.13), and there
      were no differences between the groups in terms of pain at 1 year (deltoid-split
      1.8; 95% CI, 1.2-1.4 versus deltopectoral 2.5; 95% CI, 1.7-3.2; p = 0.14). No
      learning-curve effects were noted; fluoroscopy use during surgery and function
      and pain scores during followups were similar among the first 30 patients and the
      next 30 patients treated in each group. CONCLUSIONS: The treatment of proximal
      humeral fractures with a polyaxial locking plate is reliable using both
      approaches. For a definitive recommendation for one of these approaches, further
      studies with appropriate sample size are necessary. LEVEL OF EVIDENCE: Level II,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 24326595
TI  - Heterogeneity of outcome with single-agent carfilzomib: all relapsed/refractory
      myelomas are not created equal.

PMID- 24326596
TI  - First synthesis and aggregation behaviour of periconjugated triazoliumfullerene.
AB  - Triazoliumfullerene was first prepared by the [3+2] cycloaddition of in situ
      generated 1,3-diaza-2-azoniaallene with fullerene and was characterized by the
      dispersed positive charge over the fullerene sphere associated with
      periconjugation. This new type of amphiphilic fullerene tended to form vesicles
      and crystalline aggregates after the casting of THF or MeOH solutions. 

PMID- 24326594
TI  - Biceps detachment decreases joint damage in a rotator cuff tear rat model.
AB  - BACKGROUND: Pathology in the long head of the biceps tendon often occurs in
      patients with rotator cuff tears. Arthroscopic tenotomy is the most common
      treatment. However, the role of the long head of the biceps at the shoulder and
      the consequences of surgical detachment on the remaining shoulder structures
      remain unknown. QUESTIONS/PURPOSES: We hypothesized that detachment of the long
      head of the biceps, in the presence of supraspinatus and infraspinatus tears,
      would decrease shoulder function and decrease mechanical and histologic
      properties of both the subscapularis tendon and the glenoid articular cartilage.
      METHODS: We detached the supraspinatus and infraspinatus or the supraspinatus,
      infraspinatus, and long head of the biceps after 4 weeks of overuse in a rat
      model. Animals were gradually returned to overuse activity after detachment. At 8
      weeks, the subscapularis and glenoid cartilage biomechanical and histologic
      properties were evaluated and compared. RESULTS: The supraspinatus,
      infraspinatus, and long head of the biceps group had a decreased change in
      braking and vertical force. [corrected]. This group also had an increased upper
      and lower subscapularis modulus but without any differences in glenoid cartilage
      modulus. Finally, this group had a significantly lower cell density in both the
      upper and lower subscapularis tendons, although cartilage histology was not
      different. CONCLUSIONS: Detachment of the long head of the biceps tendon in the
      presence of a posterior-superior cuff tear resulted in improved shoulder function
      and less joint damage in this animal model. CLINICAL RELEVANCE: This study
      provides evidence in an animal model that supports the use of tenotomy for the
      management of long head of the biceps pathology in the presence of a two-tendon
      cuff tear. However, long-term clinical trials are required.

PMID- 24326597
TI  - Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to
      lopinavir/ritonavir or nonnucleoside reverse transcriptase inhibitor therapy.
AB  - BACKGROUND: In the Prevention of Malaria and HIV disease in Tororo pediatrics
      trial, HIV-infected Ugandan children randomized to receive lopinavir/ritonavir
      (LPV/r)-based antiretroviral therapy (ART) experienced a lower incidence of
      malaria compared with children receiving nonnucleoside reverse transcriptase
      inhibitor (NNRTI)-based ART. Here we present the results of the noninferiority
      analysis of virologic efficacy and comparison of immunologic outcomes. METHODS:
      ART-naive or -experienced (HIV RNA <400 copies/mL) children aged 2 months to 6
      years received either LPV/r or NNRTI-based ART. The proportion of children with
      virologic suppression (HIV RNA <400 copies/mL) at 48 weeks was compared using a
      prespecified noninferiority margin of -11% in per-protocol analysis. Time to
      virologic failure by 96 weeks, change in CD4 counts and percentages, and
      incidence of adverse event rates were also compared. RESULTS: Of 185 children
      enrolled, 91 initiated LPV/r and 92 initiated NNRTI-based ART. At baseline, the
      median age was 3.1 years (range, 0.4-5.9), and 131 (71%) children were ART-naive.
      The proportion of children with virologic suppression at 48 weeks was 80% (67/84)
      in the LPV/r arm vs. 76% (59/78) in the NNRTI arm, a difference of 4% (95%
      confidence interval: -9% to +17%). Time to virologic failure, CD4 changes, and
      the incidence of Division of AIDS grade III/IV adverse events were similar
      between arms. CONCLUSIONS: LPV/r-based ART was not associated with worse
      virologic efficacy, immunologic efficacy, or adverse event rates compared with
      NNRTI-based ART. Considering these results and the reduction in malaria incidence
      associated with LPV/r previously reported for this trial, wider use of LPV/r to
      treat HIV-infected African children in similar malaria-endemic settings could be
      considered.

PMID- 24326598
TI  - Antiretroviral therapy restores age-dependent loss of resting memory B cells in
      young HIV-infected Zambian children.
AB  - BACKGROUND: Antiretroviral therapy (ART) is associated with incomplete
      restoration of resting memory B (RMB) cell percentages in adults infected with
      HIV, but the effects on RMB cells in children are less well defined, in part
      because changes in RMB cell percentages are confounded by the development and
      maturation of the RMB cell pool. The objective of this study was to assess the
      effect of age at ART initiation on RMB cell percentages over time in HIV-infected
      Zambian children. METHODS: RMB cell percentages (CD19CD21CD27) were measured by
      flow cytometry in 146 HIV-infected Zambian children (9-120 months old) at
      baseline and at 3-month intervals after ART initiation and in 34 control children
      at a single study visit. RESULTS: RMB cell percentages among untreated HIV
      infected children younger than 24 months did not differ from those of control
      children (P = 0.97). Among HIV-infected children older than 24 months of age,
      however, each 12-month increase in age at ART initiation was associated with a
      1.8% decrease in RMB cell percentage. In contrast, RMB cell percentages in
      control children up to 48 months increased 4.4% with each 12-month increase in
      age. After 12 months of ART, children aged 24-60 months had a significant
      increase in RMB cell percentages that no longer differed from those of control
      children. CONCLUSIONS: Initiation of ART in 2- to 5-year-old HIV-infected
      children resulted in reconstitution of RMB cell percentages to levels similar to
      control children and may help restore normal development and maintenance of B
      cell immunity.

PMID- 24326599
TI  - Tracing of patients lost to follow-up and HIV transmission: mathematical modeling
      study based on 2 large ART programs in Malawi.
AB  - OBJECTIVE: Treatment as prevention depends on retaining HIV-infected patients in
      care. We investigated the effect on HIV transmission of bringing patients lost to
      follow-up (LTFU) back into care. DESIGN: Mathematical model. METHODS: Stochastic
      mathematical model of cohorts of 1000 HIV-infected patients on antiretroviral
      therapy, based on the data from 2 clinics in Lilongwe, Malawi. We calculated
      cohort viral load (sum of individual mean viral loads each year) and used a
      mathematical relationship between viral load and transmission probability to
      estimate the number of new HIV infections. We simulated 4 scenarios: "no LTFU"
      (all patients stay in care), "no tracing" (patients LTFU are not traced),
      "immediate tracing" (after missed clinic appointment), and "delayed tracing"
      (after 6 months). RESULTS: About 440 of 1000 patients were LTFU over 5 years.
      Cohort viral loads (million copies/mL per 1000 patients) were 3.7 [95% prediction
      interval (PrI), 2.9-4.9] for no LTFU, 8.6 (95% PrI, 7.3-10.0) for no tracing, 7.7
      (95% PrI, 6.2-9.1) for immediate, and 8.0 (95% PrI, 6.7-9.5) for delayed tracing.
      Comparing no LTFU with no tracing, the number of new infections increased from 33
      (95% PrI, 29-38) to 54 (95% PrI, 47-60) per 1000 patients. Immediate tracing
      prevented 3.6 (95% PrI, -3.3 to 12.8) and delayed tracing 2.5 (95% PrI, -5.8 to
      11.1) new infections per 1000. Immediate tracing was more efficient than delayed
      tracing: to 116 and 142 tracing efforts, respectively, were needed prevent 1 new
      infection. CONCLUSIONS: Tracing of patients LTFU enhances the preventive effect
      of antiretroviral therapy, but the number of transmissions prevented is small.

PMID- 24326601
TI  - Optimizing the use of surveillance data for monitoring the care status of persons
      recently diagnosed with HIV in NYC.
AB  - BACKGROUND: Comprehensive laboratory reporting of CD4 and viral load (VL) tests
      to surveillance has been used to assess HIV care-related outcomes at the
      population level, but their validity for this purpose has not been
      comprehensively evaluated. OBJECTIVE: Assess performance characteristics and
      validity of surveillance-based measures of linkage to and establishment of HIV
      primary care among HIV-infected persons in the first 12 months after diagnosis
      using medical record (MR) data on outpatient HIV primary care visits as the gold
      standard. METHODS: All patients diagnosed with HIV in 2009 at 24 New York City
      high-volume, HIV diagnostic and treatment facilities who linked to care within 12
      months at the same site as defined by the presence of >=1 CD4/VL report received
      by surveillance were selected for MR review to confirm linkage to outpatient HIV
      primary care within the first year. All HIV care visit dates were abstracted and
      considered associated with a surveillance laboratory report, if within 14 days of
      a care visit. The proportion linking to care according to the MR was compared
      with the proportion linking per CD4/VL tests reported to surveillance. Four
      measures of the establishment of outpatient HIV primary care in the first year
      were assessed: (1) sustained care (first visit within 3 months; second visit, 3-9
      months later), (2) continuous care (2 visits at least 90 days apart), (3)
      trimester visits (visit in each 4-month period), and (4) visit constancy (visit
      in each 3-month period). The validity of surveillance data for measuring this
      outcome was assessed by comparing results for each of the 4 measures calculated
      using surveillance data to those calculated using MR data. RESULTS: Of the 782
      patients selected, 20% (N = 157) of patients did not link to outpatient HIV
      primary care at the co-located care facility within 12 months of diagnosis. Half
      (48.5%) of patients' care visits after linkage did not have an associated CD4/VL
      reported to surveillance. Of the 4 establishment measures, sustained and
      continuous care had the highest agreement with MR (86.6% and 88.8%, respectively)
      as compared with the trimester visits and visit constancy (77.8% and 72.8%,
      respectively). CONCLUSIONS: Surveillance data overestimated linkage rates but
      underestimated the frequency of HIV care in the first year after HIV diagnosis.
      Of the 4 measures of establishment of HIV care evaluated, "sustained care" is
      best suited for measurement using surveillance data because of its high level of
      agreement with MR data and close alignment with national standards for timely
      linkage and flexible follow-up.

PMID- 24326600
TI  - Predictors of first follow-up HIV testing for couples' voluntary HIV counseling
      and testing in Ndola, Zambia.
AB  - INTRODUCTION: We describe predictors of first follow-up testing for concordant
      negative and discordant couples seeking joint voluntary HIV counseling and
      testing in Ndola, Zambia, where cohabiting couples account for an estimated two
      thirds of incident HIV infections. METHODS: Demographic and serostatus data were
      collected from couples' voluntary HIV testing and counseling and follow-up
      testing services implemented in government clinics. We calculated follow-up
      testing rates by serostatus and compared rates before and after the introduction
      of a Good Health Package (GHP). RESULTS: The follow-up testing rate from May 2011
      to December 2012 was 12.2% for concordant negative (M-F-) couples and 24.5% for
      discordant (M+F- or M-F+) couples. Significant predictors of follow-up testing in
      multivariate analyses included increasing age of the man [adjusted odds ratio
      (aOR) = 1.02 per year] and the woman (aOR = 1.02 per year), and either partner
      being HIV+ (aOR = 2.57 for HIV+ man, aOR = 1.89 for HIV+ woman). The man (aOR =
      1.29) and the couple (aOR = 1.22) having been previously tested for HIV were
      predictive of follow-up testing among concordant negative couples. Introduction
      of a GHP increased follow-up testing among discordant (aOR = 2.93) and concordant
      negative (aOR = 2.06) couples. CONCLUSIONS: A low-cost GHP, including prevention,
      screening, and treatment for common causes of morbidity and mortality resulted in
      increased follow-up testing rates among HIV discordant and concordant negative
      couples. Overall follow-up testing rates remain low, and efforts to increase
      these rates are necessary to ensure linkage to combination prevention, reduce HIV
      transmission within couples, and identify seroconversions promptly. Further
      investigation of low-cost sustainable incentives and other factors influencing
      follow-up HIV testing for couples is needed.

PMID- 24326602
TI  - Qualitative assessment of the integration of HIV services with infant routine
      immunization visits in Tanzania.
AB  - BACKGROUND: In 2009, a project was implemented in 8 primary health clinics
      throughout Tanzania to explore the feasibility of integrating pediatric HIV
      prevention services with routine infant immunization visits. METHODS: We
      conducted interviews with 64 conveniently sampled mothers of infants who had
      received integrated HIV and immunization services and 16 providers who delivered
      the integrated services to qualitatively identify benefits and challenges of the
      intervention midway through project implementation. FINDINGS: Mothers' perceived
      benefits of the integrated services included time savings, opportunity to learn
      their child's HIV status and receive HIV treatment, if necessary. Providers'
      perceived benefits included reaching mothers who usually would not come for only
      HIV testing. Mothers and providers reported similar challenges, including
      mothers' fear of HIV testing, poor spousal support, perceived mandatory HIV
      testing, poor patient flow affecting confidentiality of service delivery, heavier
      provider workloads, and community stigma against HIV-infected persons; the latter
      a more frequent theme in rural compared with urban locations. INTERPRETATION:
      Future scale-up should ensure privacy of these integrated services received at
      clinics and community outreach to address stigma and perceived mandatory testing.
      Increasing human resources for health to address higher workloads and longer
      waiting times for proper patient flow is necessary in the long term.

PMID- 24326603
TI  - The impact of a food assistance program on nutritional status, disease
      progression, and food security among people living with HIV in Uganda.
AB  - BACKGROUND: Although the last decade has seen increased access to antiretroviral
      therapy across the developing world, widespread food insecurity and
      undernutrition continue to compromise an effective response to the AIDS epidemic.
      Limited evidence exists on the potential benefit of food security and nutrition
      interventions to people living with HIV (PLHIV). METHODS: We capitalized on an
      existing intervention to PLHIV in Uganda and conducted a prospective quasi
      experimental study evaluating the impact of a monthly household food basket,
      provided to food insecure antiretroviral therapy-naive PLHIVs for 12 months. The
      outcomes of interest measured at baseline and follow-up were nutritional status
      [body mass index; mid-upper arm circumference and hemoglobin (Hb)
      concentrations], disease severity (CD4 count), and 2 measures of food security:
      diet quality (Individual Dietary Diversity Score) and food access (Household Food
      Insecurity Access Scale). We used difference-in-difference propensity score
      matching to examine the impact of food assistance. RESULTS: Over 12 months, food
      assistance significantly increased body mass index by 0.6 kg/m (P < 0.01) and mid
      upper arm circumference by 6.7 mm (P < 0.05). We found no impact on CD4 count, Hb
      concentrations, or Individual Dietary Diversity Score. Restricting the analysis
      to individuals with CD4 counts of greater than 350 cells per microliter, there
      were significant impacts on Hb concentrations (1.0 g/dL; P < 0.05). At the
      household level, food assistance increased the Household Food Insecurity Access
      Scale, by 2.1 points (P < 0.01). CONCLUSIONS: This study demonstrates the
      potential for food assistance programming to be part of the standard of care for
      PLHIV in areas of widespread food insecurity.

PMID- 24326604
TI  - Clinical versus rapid molecular HIV diagnosis in hospitalized African infants: a
      randomized controlled trial simulating point-of-care infant testing.
AB  - OBJECTIVE: Many African infants fail to receive their diagnostic HIV molecular
      test results and subsequently, antiretroviral therapy (ART). To determine whether
      a point-of-care molecular HIV test increases ART access for hospitalized Malawian
      infants, we simulated a point-of-care test using rapid HIV RNA polymerase chain
      reaction (Rapid PCR) and compared patient outcomes with an optimized standard
      care that included assessment with the World Health Organization clinical
      algorithm for HIV infection plus a DNA PCR with a turnaround time of several
      weeks (standard care). DESIGN: Randomized controlled trial. METHODS: Hospitalized
      HIV-exposed Malawian infants aged <12 months were randomized into Rapid PCR or
      standard care. Rapid PCR infants obtained molecular test results within 48 hours
      to facilitate immediate ART, similar to a point-of-care test. Standard care
      infants meeting clinical criteria were also offered inpatient ART. The primary
      outcome was appropriate in-hospital ART for DNA or RNA PCR-confirmed HIV-infected
      infants. RESULTS: Three hundred infants were enrolled. A greater proportion of
      HIV-infected infants receiving Rapid PCR, versus standard care, started inpatient
      ART (72.3% vs 47.8%, P = 0.016). Among molecular test-negative infants, 26.9%
      receiving standard care unnecessarily initiated inpatient ART, versus 0.0%
      receiving Rapid PCR (P < 0.001). Rapid PCR modestly reduced the median days to
      ART (3.0 vs 6.5, P = 0.001) but did not influence outpatient follow-up for HIV
      infected infants (78.1% vs 82.4%, P = 0.418). CONCLUSIONS: Rapid PCR, versus an
      optimized standard care, increased the proportion of hospitalized HIV-infected
      infants initiating ART and reduced ART exposure in molecular test-negative
      infants, without meaningfully impacting time to ART initiation or follow-up
      rates.

PMID- 24326605
TI  - Linkage to HIV care and antiretroviral therapy by HIV testing service type in
      Central Mozambique: a retrospective cohort study.
AB  - BACKGROUND: Access to antiretroviral therapy (ART) has increased dramatically in
      resource-limited settings since its introduction a decade ago. However, ART
      coverage remains low in countries with the highest disease burden, which may be
      partially explained by poor testing to care linkages. HIV testing service may
      impact early attrition in the HIV treatment cascade. METHODS: A retrospective
      cohort study was conducted in 18 clinics in central Mozambique using routine
      patient data and monthly reports. Patients referred from voluntary counseling and
      testing (VCT) were compared with those referred from prevention of mother-to
      child transmission (PMTCT) for 3 outcomes: (1) enrollment at an HIV clinic <=30
      days after testing HIV positive, (2) CD4 test <=30 days after enrollment, and (3)
      ART initiation <=90 days after first CD4 test. RESULTS: Patient retention in the
      HIV care system dropped at each step from HIV testing to ART initiation.
      Enrollment in HIV care was not significantly different between PMTCT and VCT
      [risk ratio (RR) = 0.84, 0.72 < RR < 1.02]. Women tested in PMTCT were less
      likely to have a CD4 test <=30 days after enrollment when adjusting for age,
      education level, and marital status (adjusted RR = 0.84, 0.70 < RR < 1.00), and
      were less likely to initiate ART <=90 days after their first CD4 test when
      adjusting for age, education, and marital status (adjusted RR = 0.56, 0.44 < RR <
      0.71). CONCLUSIONS: Poor linkages between HIV testing and care hamper efforts to
      improve coverage for HIV care and treatment services. Increased loss to follow-up
      among women diagnosed in PMTCT relative to VCT is worrisome and merits further
      qualitative research and programmatic attention.

PMID- 24326606
TI  - Increase in single-tablet regimen use and associated improvements in adherence
      related outcomes in HIV-infected women.
AB  - INTRODUCTION: The use of single-tablet antiretroviral therapy (ART) regimens and
      its implications on adherence among HIV-infected women have not been well
      described. METHODS: Participants were enrolled in the Women's Interagency HIV
      Study, a longitudinal study of HIV infection in US women. We examined semiannual
      trends in single-tablet regimen use and ART adherence, defined as self-reported
      95% adherence in the past 6 months, during 2006-2013. In a nested cohort study,
      we assessed the comparative effectiveness of a single-tablet versus a multiple
      tablet regimen with respect to adherence, virologic suppression, quality of life,
      and AIDS-defining events, using propensity score matching to account for
      demographic, behavioral, and clinical confounders. We also examined these
      outcomes in a subset of women switching from a multiple- to single-tablet regimen
      using a case-crossover design. RESULTS: We included 15,523 person-visits,
      representing 1727 women (53% black, 29% Hispanic, 25% IDU, median age 47). Use of
      single-tablet regimens among ART users increased from 7% in 2006% to 27% in 2013;
      adherence increased from 78% to 85% during the same period (both P < 0.001).
      Single-tablet regimen use was significantly associated with increased adherence
      (adjusted risk ratio: 1.05; 95% confidence interval: 1.03 to 1.08) and virologic
      suppression (risk ratio: 1.06; 95% confidence interval: 1.01 to 1.11), while
      associations with improved quality of life and fewer AIDS-defining events did not
      achieve statistical significance. Similar findings were observed among the subset
      of switchers. CONCLUSIONS: Single-tablet regimen use was associated with
      increased adherence and virologic suppression. Despite this, 15% of women
      prescribed ART were still not optimally adherent; additional interventions are
      needed to maximize therapeutic benefits.

PMID- 24326607
TI  - Epidemiology of head and neck squamous cell cancer among HIV-infected patients.
AB  - BACKGROUND: HIV-infected individuals have a higher incidence of head and neck
      cancer (HNC). METHODS: Case series of 94 HIV-infected HNC patients (HIV-HNC) at 6
      tertiary care referral centers in the US between 1991 and 2011. Clinical and risk
      factor data were abstracted from the medical record. Risk factors for survival
      were analyzed using Cox proportional hazard models. Human papillomavirus (HPV)
      and p16 testing was performed in 46 tumors. Findings were compared with
      Surveillance Epidemiology and End Results HNC (US-HNC) data. RESULTS: This study
      represents the largest HIV-HNC series reported to date. HIV-HNC cases were more
      likely than US-HNC to be male (91% vs. 68%), younger (median age, 50 vs. 62
      years), nonwhite (49% vs. 18%), and current smokers (61% vs. 18%). Median HIV-HNC
      survival was not appreciably lower than US-HNC survival (63 vs. 61 months). At
      diagnosis, most cases were currently on highly active antiretroviral therapy
      (77%) but had detectable HIV viremia (99%), and median CD4 was 300 cells per
      microliter (interquartile range = 167-500). HPV was detected in 30% of HIV-HNC
      and 64% of HIV-oropharyngeal cases. Median survival was significantly lower among
      those with CD4 counts <=200 than >200 cells per microliter at diagnosis (16.1 vs.
      72.8 months, P < 0.001). In multivariate analysis, poorer survival was associated
      with CD4 <100 cells per microliter [adjusted hazard ratio (aHR) = 3.09, 95%
      confidence interval (CI): 1.15 to 8.30], larynx/hypopharynx site (aHR = 3.54, 95%
      CI: 1.34 to 9.35), and current tobacco use (aHR = 2.54, 95% CI: 0.96 to 6.76).
      CONCLUSIONS: Risk factors for the development of HNC in patients with HIV
      infection are similar to the general population, including both HPV-related and
      tobacco/alcohol-related HNC.

PMID- 24326609
TI  - Dementia (including Alzheimer's disease) can be prevented: statement supported by
      international experts.

PMID- 24326608
TI  - Discontinuation of antiretroviral therapy among adults receiving HIV care in the
      United States.
AB  - BACKGROUND: Continuous antiretroviral therapy (ART) is important for maintaining
      viral suppression. This analysis estimates prevalence of and reason for ART
      discontinuation. METHODS: Three-stage sampling was used to obtain a nationally
      representative, cross-sectional sample of HIV-infected adults receiving HIV care.
      Face-to-face interviews and medical record abstractions were collected from June
      2009 to May 2010. Data were weighted based on known probabilities of selection
      and adjusted for nonresponse. Patient characteristics of ART discontinuation,
      defined as not currently taking ART, stratified by provider-initiated versus non
      provider-initiated discontinuation, were examined. Weighted logistic regression
      models predicted factors associated with ART discontinuation. RESULTS: Of adults
      receiving HIV care in the United States who reported ever initiating ART, 5.6%
      discontinued treatment. Half of those who discontinued treatment reported
      provider-initiated discontinuation. Provider-initiated ART discontinuation
      patients were more likely to have a nadir CD4 >= 200 cells per cubic millimeter.
      Non-provider-initiated ART discontinuation patients were more likely to have
      unmet need for supportive services and to have not received HIV care in the past
      3 months. Among all patients who discontinued, younger age, female gender, not
      having continuous health insurance, incarceration, injection drug use, nadir CD4
      count >= 2 00 cells per cubic millimeter, unmet need for supportive services, no
      care in the past 3 months and HIV diagnosis >= 5 years before interview were
      independently associated with ART discontinuation. CONCLUSIONS: These findings
      inform development of interventions to increase ART persistence by identifying
      groups at increased risk of ART discontinuation. Evidence-based interventions
      targeting vulnerable populations are needed and are increasingly important as
      recent HIV treatment guidelines have recommended universal ART.

PMID- 24326612
TI  - An orthotopic bladder cancer model for gene delivery studies.
AB  - Bladder cancer is the second most common cancer of the urogenital tract and novel
      therapeutic approaches that can reduce recurrence and progression are needed. The
      tumor microenvironment can significantly influence tumor development and therapy
      response. It is therefore often desirable to grow tumor cells in the organ from
      which they originated. This protocol describes an orthotopic model of bladder
      cancer, in which MB49 murine bladder carcinoma cells are instilled into the
      bladder via catheterization. Successful tumor cell implantation in this model
      requires disruption of the protective glycosaminoglycan layer, which can be
      accomplished by physical or chemical means. In our protocol the bladder is
      treated with trypsin prior to cell instillation. Catheterization of the bladder
      can also be used to deliver therapeutics once the tumors are established. This
      protocol describes the delivery of an adenoviral construct that expresses a
      luciferase reporter gene. While our protocol has been optimized for short-term
      studies and focuses on gene delivery, the methodology of mouse bladder
      catheterization has broad applications. 

PMID- 24326613
TI  - Effects of heme iron enriched peptide on iron deficiency anemia in rats.
AB  - The present study aims to investigate whether a daily intake of heme iron
      enriched peptide obtained from bovine hemoglobin is effective in alleviating iron
      deficiency anemia (IDA). Wistar rats were randomly divided into six groups: a
      control group, an anemic group not treated, and anemic groups treated with FeSO4
      or with the heme iron enriched peptide at low, moderate or high doses. The rats
      in the anemic groups were fed on a low-iron diet to establish the iron deficiency
      anemia model. After the model had been established, different doses of heme iron
      enriched peptide were given to the rats once a day via intragastric
      administration. After the iron supplement administration, it was observed that
      heme iron enriched peptide had effective restorative action returning the
      hemoglobin, red blood cells, hematocrit, mean corpuscular volume, mean
      corpuscular hemoglobin concentration and serum iron in IDA animals to normal
      values or better. In addition, compared with FeSO4, higher Fe bioavailability and
      fewer side effects were observed. The rats in the moderate dose group had the
      highest apparent Fe absorption. Moreover, in vivo antioxidant activity was also
      observed, enhancing the activities of antioxidant enzymes and reduced
      malondialdehyde levels in IDA rats. Furthermore, the heme iron enriched peptide
      also exhibited strong in vitro antioxidant activities. In conclusion, heme iron
      enriched peptide significantly alleviated iron deficiency anemia, and exhibited
      strong in vitro and in vivo antioxidant activities. This suggests that heme iron
      enriched peptide might be exploited as a safe, efficient new iron supplement. 

PMID- 24326614
TI  - Lentiviral vectors enveloped with rabies virus glycoprotein can be used as a
      novel retrograde tracer to assess nerve recovery in rat sciatic nerve injury
      models.
AB  - Retrograde labeling has become the new "gold standard" technique to evaluate the
      recovery of injured peripheral nerves. In this study, lentiviral vectors with
      rabies virus glycoprotein envelop (RABV-G-LV) and RFP genes are injected into
      gastrocnemius muscle to determine the location of RFP in sciatic nerves. We then
      examine RFP expression in the L4-S1 spinal cord and sensory dorsal root ganglia
      and in the rat sciatic nerve, isolated Schwann cells, viral dose to expression
      relationship and the use of RABV-G-LV as a retrograde tracer for regeneration in
      the injured rat sciatic nerve. VSV-G-LV was used as control for viral envelope
      specificity. Results showed that RFP were positive in the myelin sheath and
      lumbar spinal motorneurons of the RABV-G-LV group. RFP gene could be detected
      both in myelinated Schwann cells and lumbar spinal motor neurons in the RABV-G-LV
      group. Schwann cells isolated from the RABV-G-LV injected postnatal Sprague
      Dawley rats were also RFP-gene positive. All the results obtained in the VSV-G-LV
      group were negative. Distribution of RFP was unaltered and the level of RFP
      expression increasing with time progressing. RABV-G-LV could assess the amount of
      functional regenerating nerve fibers two months post-operation in the four
      models. This method offers an easy-operated and consistent standardized approach
      for retrograde labeling regenerating peripheral nerves, which may be a
      significant supplement for the previous RABV-G-LV-related retrograde labeling
      study. 

PMID- 24326615
TI  - Dysfunction of neuronal calcium signalling in neuroinflammation and
      neurodegeneration.
AB  - Neurodegeneration has been increasingly recognised as the leading structural
      correlate of disability progression in autoimmune diseases such as multiple
      sclerosis. Since calcium signalling is known to regulate the development of
      degenerative processes in many cell types, it is believed to play significant
      roles in mediating neurodegeneration. Because of its function as a major juncture
      linking various insults and injuries associated with inflammatory attack on
      neuronal cell bodies and axons, it provides potential for the development of
      neuroprotective strategies. This is of great significance because of the lack of
      neuroprotective agents presently available to supplement the current array of
      immunomodulatory treatments. In this review, we summarise the role that various
      calcium channels and pumps have been shown to play in the development of
      neurodegeneration under inflammatory autoimmune conditions. The identification of
      suitable targets might also provide insights into applications in non
      inflammatory neurodegenerative diseases. 

PMID- 24326616
TI  - Changes in epidermal growth factor receptor expression during chemotherapy in non
      small cell lung cancer.
AB  - BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as
      cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC)
      patients with high EGFR expression. The EGFR expression may be heterogeneously
      distributed within tumors, and small biopsies may thus not accurately reveal the
      EGFR expression. In addition, EGFR expression may also change during
      chemotherapy. The current study investigates the magnitude of these two issues.
      MATERIALS AND METHODS: EGFR expression in diagnostic biopsies and resection
      specimen was compared in 53 NSCLC patients stage T1-4N0-1M0 treated with surgery
      without preceding chemotherapy (OP group), and 65 NSCLC patients stage T1-3N0-2M0
      (NAC group) treated with preoperative carboplatin and paclitaxel in order to
      evaluate the discordance of EGFR expression between samples. RESULTS: Discordance
      between tumors dichotomized according to EGFR expression (high: H-score >=200;
      low: H-score <200) in diagnostic biopsies and immediate resection specimens was
      25 % in the OP group and 33 % in the NAC group (p = 0.628). Five (9 %) of primary
      tumors in the OP group and 4 (13 %) in the NAC group had increased EGFR
      expression in the resection specimens as compared to the diagnostic biopsies (p =
      0.583). A decrease in EGFR expression was observed in 6 (11 %) in the OP group
      and 7 (23 %) in the NAC group (p = 0.148). CONCLUSION: EGFR expression in 25 % of
      diagnostic biopsies may potentially not be accurate compared to the prevailing
      pattern in the whole tumor based on the larger resection specimens. This may
      potentially be an obstacle for proper use of antibodies targeting the EGFR in
      NSCLC. EGFR expression does, however, not change significantly during paclitaxel
      and carboplatin and rebiopsies in order to decide on anti-EGFR antibody therapy
      following chemotherapy do not seem warranted.

PMID- 24326617
TI  - Diabetes care and its association with glycosylated hemoglobin level.
AB  - BACKGROUND: This article examines the associations between patients' source of
      most help with diabetes care and their glycosylated hemoglobin (A1C) levels. The
      extent to which differences in A1C by source of most help could be explained by
      perceived levels of total social support, sociodemographics, and medication
      adherence were also assessed. METHODS: A cross-sectional study of 205 adults with
      type 2 diabetes mellitus who completed a clinic survey that included questions
      about perceived social support, who provides the most support with their diabetes
      care, and medication adherence. The most recent A1C was abstracted from medical
      records. RESULTS: The mean (standard deviation) age of participants was 61 (12.3)
      years, 43.9% were male, 37.1% African American. After adjustment for age, sex,
      race, marital status, education, diabetes duration, and medication adherence, the
      means (95% confidence intervals) A1C by source of most help were 9.4 (8.4-10.4)
      for nonspouse family or friend, 8.2 (7.3-9.1) for health care worker, 8.2 (7.2
      9.1) for self-reliant, and 8.1 (7.1-9.0) for spouse. A1C was significantly higher
      for nonspouse family or friend compared with all other groups (P < 0.01 for each
      comparison). Differences in A1C by source of most help could not be explained by
      differences in total social support or medication adherence. CONCLUSIONS:
      Patients reporting a nonspouse family member or friend as their source of most
      help with their diabetes management had worse glycemic control than patients
      reporting all other sources of help.

PMID- 24326618
TI  - The differential diagnosis of hypoglycorrhachia in adult patients.
AB  - OBJECTIVES: Hypoglycorrhachia, a low glucose level in the cerebrospinal fluid
      (CSF), can suggest bacterial, fungal or tuberculous meningitis. When tests for
      these common infectious etiologies are negative, many clinicians are unsure of
      which diagnoses to consider, resulting in delayed treatment. The authors analyzed
      the diagnoses associated with hypoglycorrhachia to determine their relative
      frequencies at our institution and summarized all the diagnoses associated with
      hypoglycorrhachia in the literature. METHODS: Retrospective analysis of adults
      with hypoglycorrhachia at a tertiary care teaching hospital over a 5-year period.
      Inclusion criteria included CSF glucose <40 mg/dL and age 18 years or older.
      Exclusion criteria included CSF/serum glucose >=0.6. RESULTS: Eighty-nine unique
      hypoglycorrhachia episodes were identified. The most common etiologies among all
      episodes of hypoglycorrhachia were bacterial meningitis (24%), fungal meningitis
      (15%), stroke/bleed (13%), malignancy (11%), viral meningitis (6%),
      neurosarcoidosis (4%), neurosyphilis (4%) and cerebral toxoplasmosis (3%). The
      most common etiology was fungal meningitis (38%) among HIV-infected patients and
      bacterial meningitis (62%) among neurosurgery patients. However, in patients
      without HIV or neurosurgical history, noninfectious etiologies (stroke/bleed,
      24%; malignancy, 22%) were most common. CONCLUSIONS: Many diagnoses, both
      infectious and noninfectious, lead to hypoglycorrhachia and must be considered in
      the differential diagnosis.

PMID- 24326619
TI  - Metformin-associated lactic acidosis.
AB  - : Metformin is the most commonly prescribed oral antidiabetic agent. Despite a
      good safety profile in most patients with diabetes, the risk of metformin
      associated lactic acidosis is real if safety guidelines are ignored. Experience
      with 3 cases of metformin-associated lactic acidosis is reported. Two cases were
      caused by inappropriate use of metformin in the presence of renal, cardiac and
      hepatic failure and 1 case followed an intentional overdose. The literature was
      reviewed on the clinical presentation, prevalence, pathogenesis, prognosis and
      management of metformin-associated lactic acidosis. This report highlights the
      importance of proper patient selection, clinical and laboratory monitoring and
      recommendation on when to stop the drug in ambulatory and hospitalized patients
      to prevent this unusual but potentially lethal complication. 

PMID- 24326620
TI  - Protein metabolism: A channel for ERAD.

PMID- 24326621
TI  - Adult intestinal stem cells: critical drivers of epithelial homeostasis and
      regeneration.
AB  - Small populations of adult stem cells are responsible for the remarkable ability
      of the epithelial lining of the intestine to be efficiently renewed and repaired
      throughout life. The recent discovery of specific markers for these stem cells,
      together with the development of new technologies to track endogenous stem cell
      activity in vivo and to exploit their ability to generate new epithelia ex vivo,
      has greatly improved our understanding of stem cell-driven homeostasis,
      regeneration and cancer in the intestine. These exciting new insights into the
      biology of intestinal stem cells have the potential to accelerate the development
      of stem cell-based therapies and ameliorate cancer treatments. 

PMID- 24326624
TI  - DABCO catalyzed cross-Rauhut-Currier/transesterification reactions of activated
      alkenes with phenyl acrylates: scope and mechanistic insight.
AB  - DABCO catalyzed the cross-Rauhut-Currier/transesterification reaction of alpha
      cyano-alpha,beta-unsaturated ketones and aryl acrylates was discovered. The
      reaction rate law was determined by an integral method under pseudo-first-order
      reaction conditions, which assisted in proposing the mechanism of cross-Rauhut
      Currier reaction promoted by Bronsted acid and establishing the rate-determining
      step. 

PMID- 24326622
TI  - The return of the nucleus: transcriptional and epigenetic control of autophagy.
AB  - Autophagy is a conserved process by which cytoplasmic components are degraded by
      the lysosome. It is commonly seen as a cytoplasmic event and, until now, nuclear
      events were not considered of primary importance for this process. However,
      recent studies have unveiled a transcriptional and epigenetic network that
      regulates autophagy. The identification of tightly controlled transcription
      factors (such as TFEB and ZKSCAN3), microRNAs and histone marks (especially
      acetylated Lys16 of histone 4 (H4K16ac) and dimethylated H3K9 (H3K9me2))
      associated with the autophagic process offers an attractive conceptual framework
      to understand the short-term transcriptional response and potential long-term
      responses to autophagy.

PMID- 24326623
TI  - Double-strand break repair: 53BP1 comes into focus.
AB  - DNA double-strand break (DSB) signalling and repair is crucial to preserve
      genomic integrity and maintain cellular homeostasis. p53-binding protein 1
      (53BP1) is an important regulator of the cellular response to DSBs that promotes
      the end-joining of distal DNA ends, which is induced during V(D)J and class
      switch recombination as well as during the fusion of deprotected telomeres. New
      insights have been gained into the mechanisms underlying the recruitment of 53BP1
      to damaged chromatin and how 53BP1 promotes non-homologous end-joining-mediated
      DSB repair while preventing homologous recombination. From these studies, a model
      is emerging in which 53BP1 recruitment requires the direct recognition of a DSB
      specific histone code and its influence on pathway choice is mediated by mutual
      antagonism with breast cancer 1 (BRCA1). 

PMID- 24326625
TI  - Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic
      factor in rats after permanent middle cerebral artery occlusion.
AB  - It has been well documented that exercise promotes neurological rehabilitation in
      patients with cerebral ischemia. However, the exact mechanisms have not been
      fully elucidated. This study aimed to discuss the effect of treadmill exercise on
      expression levels of 5-HT, 5-HT1A receptor (5-HT1AR) and brain derived neurophic
      factor (BDNF) in rat brains after permanent middle cerebral artery occlusion
      (pMCAO). A total of 55 rats were randomly divided into 3 groups: pMCAO group,
      pMCAO and treadmill exercise (pMCAO + Ex) group, and sham-operated group. Rats in
      pMCAO + Ex group underwent treadmill exercise for 16 days. Neurological function
      was evaluated by modified Neurological Severity Scores (mNSS). High-performance
      liquid chromatography-electrochemical detection system was used to determine the
      content of 5-HT in cortex tissues. The protein levels of 5-HT1AR, BDNF and
      synaptophysin were measured by Western blot. The mNSS in pMCAO + Ex group was
      lower than that in pMCAO group on day 19 post-MCAO (p < 0.001). The content of 5
      HT dropped to 3.81 +/- 1.86 ng/ml in pMCAO group (43.84 +/- 2.05 ng/ml in sham
      operated group), but increased in pMCAO + Ex group (10.06 +/- 1.80 ng/ml). The
      protein expressions levels of synaptophysin, 5-HT1AR and BDNF were downregulated
      after cerebral ischemia (p < 0.05), and upregulated after treadmill exercise (p <
      0.05). These results indicate that treadmill exercise improves neurologic
      function, enhances neuronal plasticity and upregulates the levels of 5-HT, 5
      HT1AR and BDNF in rats with pMCAO.

PMID- 24326626
TI  - The 2-repeat allele of the MAOA gene confers an increased risk for shooting and
      stabbing behaviors.
AB  - There has been a great deal of research examining the link between a polymorphism
      in the promoter region of the MAOA gene and antisocial phenotypes. The results of
      these studies have consistently revealed that low activity MAOA alleles are
      related to antisocial behaviors for males who were maltreated as children.
      Recently, though, some evidence has emerged indicating that a rare allele of the
      MAOA gene-that is, the 2-repeat allele-may have effects on violence that are
      independent of the environment. The current study builds on this research and
      examines the association between the 2-repeat allele and shooting and stabbing
      behaviors in a sample of males drawn from the National Longitudinal Study of
      Adolescent Health. Analyses revealed that African-American males who carry the 2
      repeat allele are significantly more likely than all other genotypes to engage in
      shooting and stabbing behaviors and to report having multiple shooting and
      stabbing victims. The limitations of the study are discussed and suggestions for
      future research are offered. 

PMID- 24326627
TI  - Hormone contraception before the first birth and endometrial cancer risk.
AB  - There is a well-documented reduction in endometrial cancer risk with combined
      oral contraceptive (COC) use. COC use before the first full-term pregnancy may
      affect breast cancer risk for decades, but this relationship has not been
      investigated in endometrial cancer. We investigated the risk for endometrial
      cancer with COC use before the first full-term pregnancy. Cases (n = 524) from a
      population-based cancer registry and age-matched controls (n = 1,032) were
      recruited between 2002 and 2006 in Alberta, Canada. Participants completed an in
      person interview and provided detailed information on exogenous hormone use and
      other risk factors. Risk reductions in endometrial cancer with COC use over the
      premenopausal years were consistent with the published literature. We also found
      evidence of a long-term, significant risk reduction in parous women with COC use
      before the first full-term pregnancy. Among parous women, >=5 years of COC use
      before a first full-term pregnancy was associated with a significant reduction in
      risk [adjusted OR, 0.42; 95% confidence interval (CI), 0.25-0.72], even if this
      exposure was a woman's only use of COCs (adjusted OR, 0.35; 95% CI, 0.18-0.68).
      Further understanding of the long-term effects of COC use may help guide the
      timing of chemoprevention efforts via COCs.

PMID- 24326629
TI  - Prevalence of HIV Infection among U.S. Hodgkin lymphoma cases.
AB  - BACKGROUND: Hodgkin lymphoma is uncommon in the U.S. general population; however,
      Hodgkin lymphoma risk is elevated in people with human immunodeficiency virus
      (HIV) infection. Thus, despite the low HIV prevalence in the United States, the
      HIV epidemic may have contributed substantially to the general population burden
      of Hodgkin lymphoma. METHODS: We used data from 14 U.S. cancer registries in the
      Surveillance, Epidemiology, and End Results Program that recorded HIV status of
      Hodgkin lymphoma cases at diagnosis during 2000 to 2010. We computed the HIV
      prevalence in Hodgkin lymphoma cases by demographic and tumor characteristics,
      the proportion of deaths among Hodgkin lymphoma cases because of HIV, and 5-year
      mortality by HIV status. RESULTS: Of 22,355 Hodgkin lymphoma cases, 848 (3.79%)
      were HIV infected at diagnosis. HIV prevalence in Hodgkin lymphoma cases was
      greater among males than females (6.0% vs. 1.2%). Among males, HIV prevalence was
      greatest among 40- to 59-year-olds (14.2%), non-Hispanic blacks (16.9%),
      Hispanics (9.9%), and among cases of lymphocyte-depleted (15.1%), and mixed
      cellularity Hodgkin lymphoma (10.5%). Eight percent of male and 1.5% of female
      Hodgkin lymphoma cases died from HIV. Five-year mortality was two-fold higher in
      HIV-infected Hodgkin lymphoma cases (36.9% vs. 17.5%). CONCLUSION: In the United
      States, a substantial proportion of lymphocyte-depleted and mixed cellularity
      Hodgkin lymphoma cases and Hodgkin lymphoma cases among non-Hispanic black,
      Hispanic, and middle-aged men are HIV infected. In addition, HIV is an important
      cause of death among Hodgkin lymphoma cases. IMPACT: Clinicians should be aware
      of the high prevalence of HIV in certain subgroups of patients with Hodgkin
      lymphoma and routine HIV testing should be recommended for all patients
      presenting with Hodgkin lymphoma.

PMID- 24326628
TI  - Epigenetic research in cancer epidemiology: trends, opportunities, and
      challenges.
AB  - Epigenetics is emerging as an important field in cancer epidemiology that
      promises to provide insights into gene regulation and facilitate cancer control
      throughout the cancer care continuum. Increasingly, investigators are
      incorporating epigenetic analysis into the studies of etiology and outcomes. To
      understand current progress and trends in the inclusion of epigenetics in cancer
      epidemiology, we evaluated the published literature and the National Cancer
      Institute (NCI)-supported research grant awards in this field to identify trends
      in epigenetics research. We present a summary of the epidemiologic studies in
      NCI's grant portfolio (from January 2005 through December 2012) and in the
      scientific literature published during the same period, irrespective of support
      from the NCI. Blood cells and tumor tissue were the most commonly used
      biospecimens in these studies, although buccal cells, cervical cells, sputum, and
      stool samples were also used. DNA methylation profiling was the focus of the
      majority of studies, but several studies also measured microRNA profiles. We
      illustrate here the current status of epidemiologic studies that are evaluating
      epigenetic changes in large populations. The incorporation of epigenomic
      assessments in cancer epidemiology studies has and is likely to continue to
      provide important insights into the field of cancer research.

PMID- 24326630
TI  - Hepatic glucose uptake is increased in association with elevated serum gamma
      glutamyl transpeptidase and triglyceride.
AB  - BACKGROUND: Subjects with fatty liver disease (FLD) can show increased hepatic 2
      deoxy-2-((18)F)fluoro-D-glucose (FDG) uptake, but the role of hepatic
      inflammation has not been explored. AIMS: We investigated whether hepatic
      inflammatory response, as implicated by elevated serum markers, is associated
      with increased liver FDG uptake in FLD. METHODS: Liver sonography and FDG
      positron emission tomography was performed in 331 asymptomatic men with
      nonalcoholic FLD (NAFLD), 122 with alcoholic FLD (AFLD), and 349 controls. Mean
      standard uptake value (SUV) of liver FDG uptake was compared to cardiac risk
      factors and serum markers of liver injury. RESULTS: Hepatic FDG mean SUV was
      increased in NAFLD (2.40 +/- 0.25) and AFLD groups (2.44 +/- 0.25) compared to
      controls (2.28 +/- 0.26; both P < 0.001). Both FLD groups also had higher serum
      gamma-glutamylranspeptidase (GGT), triglyceride (TG), hepatic transaminases, and
      LDL. High GGT and TG levels were independent determinants of increased FDG uptake
      for both FLD groups. Hepatic mean SUV significantly increased with high compared
      to low GGT for NAFLD (2.48 +/- 0.28 vs. 2.37 +/- 0.24), AFLD (2.51 +/- 0.27 vs.
      2.39 +/- 0.23), and control groups (2.39 +/- 0.22 vs. 2.26 +/- 0.26). High TG
      increased hepatic mean SUV in AFLD and control groups. Furthermore, serum GGT and
      TG levels significantly correlated to hepatic mean SUV in all three groups.
      CONCLUSIONS: Hepatic FDG uptake is closely associated with elevated TG and GGT
      regardless of the presence of FLD. Thus, inflammation response may play a major
      role in increased hepatic glucose uptake.

PMID- 24326632
TI  - [The BLOCK HF study].

PMID- 24326631
TI  - Incidence, risk factors and clinical course of pancreatic fluid collections in
      acute pancreatitis.
AB  - BACKGROUND: Acute pancreatitis is an acute inflammatory process of the pancreas
      with variable involvement of other regional tissues or remote organ systems.
      Acute fluid collections and pseudocyst formation are the most frequent
      complications of acute pancreatitis. AIMS: The aims of this study were to
      evaluate the incidence, risk factors, and clinical course of pancreatic fluid
      collections and pseudocyst formation following acute pancreatitis. METHODS: A
      prospective multicenter study was conducted in five participating centers with
      302 patients diagnosed with acute pancreatitis from January 2011 to July 2012.
      RESULTS: The incidence of pancreatic fluid collections and pseudocyst was 42.7
      and 6.3 %, respectively. Patients with fluid collections were significantly
      younger, compared to those without fluid collections (51.5 +/- 15.9 vs. 60.4 +/-
      16.5 years, P = 0.000). The proportion of alcoholic etiology (54.3 %) in patients
      with fluid collections was significantly higher compared to other etiologies (P =
      0.000). C-reactive protein (CRP) (48 h) was significantly higher in patients with
      fluid collections, compared to patients without fluid collections (39.2 +/- 77.4
      vs. 15.1 +/- 36.2 mg/dL, P = 0.016). LDH (48 h) was significantly higher in
      patients with pseudocyst formation, compared to patients with complete resolution
      (1,317.6 +/- 706.4 vs. 478.7 +/- 190.5 IU/L, P = 0.000). Pancreatic fluid
      collections showed spontaneous resolution in 69.8 % (90/129) and 84.2 % of the
      pseudocysts disappeared or decreased in size during follow up. CONCLUSIONS: Age,
      CRP (48 h), and alcohol etiology are risk factors for pancreatic fluid
      collections. LDH (48 h) appears to be a risk factor for pseudocyst formation.
      Most pseudocysts showed a decrease in size or spontaneous resolution with
      conservative management.

PMID- 24326633
TI  - [The BRUISE CONTROL study].

PMID- 24326634
TI  - [Continued oral anticoagulation during cardiac pacing: the BRUISE CONTROL study].

PMID- 24326635
TI  - [Catheter ablation of atrial fibrillation: an update from the most important
      trials].
AB  - The treatment of atrial fibrillation has greatly changed over the past decade.
      Following the pivotal observation by Haissaguerre et al. who showed the relevance
      of ectopic beats in the initiation of atrial fibrillation, percutaneous catheter
      ablation of atrial fibrillation has evolved as the most effective therapeutic
      option for the treatment of paroxysmal atrial fibrillation. The aim of this
      review is to analyze the role of catheter ablation in the management of atrial
      fibrillation on the basis of the most important trials published so far. A brief
      mention to complications and strategies for their early detection is also made. 

PMID- 24326636
TI  - [Postoperative atrial fibrillation in noncardiac thoracic surgery].
AB  - Atrial fibrillation is the most common arrhythmia in clinical practice. Although
      postoperative atrial fibrillation occurs in a small percentage of the total
      number of cases, it is associated with increased mortality, longer hospital stay
      and higher hospitalization costs, making this issue of particular relevance. The
      aim of this literature review is to describe the risk profile of this patient
      subset and to focus on the current knowledge of available prophylactic and
      therapeutic strategies. 

PMID- 24326637
TI  - [Pro-arrhythmic effect of cardiac memory in a patient with long QT syndrome].
AB  - We describe the case of a patient with a congenital long QT syndrome (LQTS) who
      showed signs of cardiac memory associated with early afterdepolarizations and
      ventricular arrhythmias, after a change in the pacing mode from VVI to AAI.
      Cardiac memory, further altering the potassium ion channel function, may have pro
      arrhythmic potential in patients with LQTS. 

PMID- 24326638
TI  - [Asymptomatic perforation of the left ventricular apex by an active-fixation
      defibrillation lead].

PMID- 24326639
TI  - [Remarks on the guideline recommendations for cardioverter-defibrillator
      implantation for primary prevention of sudden cardiac Death in patients with
      severe ventricular dysfunction. Consensus Document of the Italian Association of
      Hospital Cardiologists (ANMCO)/Italian Society of Cardiology (SIC)/Italian
      Association of Arrhythmology and Cardiac Pacing (AIAC)].
AB  - The indications for implantable cardioverter-defibrillator (ICD) therapy for the
      prevention of sudden cardiac death in patients with severe left ventricular
      dysfunction have rapidly expanded over the last 10 years on the basis of the very
      satisfying results of the numerous randomized clinical trials that have provided
      the framework for guidelines. However, the analysis of clinical practice in the
      real world has highlighted some important criticisms in the complex process of
      selection-management of those patients candidates for ICD therapy: 1)
      approximately one fourth of all ICD implantations is not justified by clinical
      evidence, 2) approximately one half of patients with an indication for ICD
      therapy do not undergo implantation, 3) the benefits from ICD therapy do not
      apply uniformly to all patients, 4) the relationship between the lifesaving
      benefit and the potential for harm of ICD therapy is still scarcely known. The
      main reason for this clinical scenario can be ascribed to the guideline
      recommendations that are based only on few standard cut-off criteria and
      therefore too generic and insufficiently detailed. This does not help
      cardiologists in their decision-making process, and results in fear, uncertainty,
      and sometimes emotional choices. The aim of this consensus document is to discuss
      current guideline recommendations and to provide the Italian cardiologists with
      the most updated information to optimize the selection of patients with severe
      left ventricular dysfunction who should receive ICD therapy. 

PMID- 24326640
TI  - [Appropriateness criteria for the treatment of atrial fibrillation with
      dronedarone: practical issues. An Italian cardiologists' expert opinion].
AB  - Antiarrhythmic agents are among the therapeutic options available for the
      treatment of atrial fibrillation when a rhythm control strategy is required.
      Although their efficacy seems to be generally comparable to that of
      nonpharmacological interventions, the use of these agents remains controversial.
      In particular, among this class of drugs, the use of dronedarone in clinical
      practice is a matter of debate. In this paper, the authors aimed to address these
      issues, involving a team of expert cardiologists who discussed about the
      potential use of dronedarone in different clinical scenarios. The RAND/UCLA
      appropriateness method was used to develop appropriateness measures for the
      optimal management of patients treated with dronedarone, by combining the best
      available scientific evidence with the collective judgment of experts. To this
      purpose, a group of experts was identified and asked to rate the benefit-to-harm
      ratio of 52 clinical scenarios. Each indication was classified as "appropriate",
      "uncertain" or "inappropriate" in accordance with the panelists' median score.
      The classification of each scenario has led to the development of several
      recommendations for clinical practice. The use of dronedarone for the management
      of paroxysmal and persistent atrial fibrillation has evolved over time: this
      antiarrhythmic drug appears to be useful not only in monitoring symptoms, but
      also in reducing hospitalization and mortality rates in patients with atrial
      fibrillation. 

PMID- 24326642
TI  - How much should doctors tell their patients?

PMID- 24326641
TI  - [The pacemaker and implantable cardioverter-defibrillator registry of the Italian
      Association of Arrhythmology and Cardiac Pacing - Annual Report 2012].
AB  - BACKGROUND: The pacemaker (PM) and implantable cardioverter-defibrillator (ICD)
      Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)
      monitors the main epidemiological data in real-world practice. The survey for the
      2012 activity collects information about demographics, clinical characteristics,
      main indications for PM/ICD therapy and device types from the Italian
      collaborating centers. METHODS: The Registry collects prospectively national PM
      and ICD implantation activity on the basis of European cards. RESULTS: PM
      Registry: data about 25 611 PM implantations were collected (18 870 first implant
      and 6741 replacements). The number of collaborating centers was 245. Median age
      of treated patients was 80 years (74 quartile I; 86 quartile III). ECG
      indications included atrioventricular conduction disorders in 41.9% of first PM
      implants, sick sinus syndrome in 26.0%, atrial fibrillation plus bradycardia in
      13.7%, other in 18.4%. Among atrioventricular conduction defects, third-degree
      atrioventricular block was the most common type (21.7% of first implants). Use of
      single-chamber PMs was reported in 29.0% of first implants, of dual-chamber PMs
      in 61.3%, of PMs with cardiac resynchronization therapy (CRT) in 1.7%, and of
      single lead atrial-synchronized ventricular stimulation (VDD/R PMs) in 8.0%. ICD
      REGISTRY: data about 16 606 ICD implantations were collected (11 393 first
      implants and 5213 replacements). The number of collaborating centers was 427.
      Median age of treated patients was 71 years (62 quartile I; 77 quartile III).
      Primary prevention indication was reported in 68.6% of first implants, secondary
      prevention in 31.4% (cardiac arrest in 9.0%). A single-chamber ICD was used in
      29.4% of first implants, dual-chamber in 37.6% and biventricular in 32.9%.
      CONCLUSIONS: The PM and ICD Registry appears fundamental for monitoring PM and
      ICD utilization on a large national scale with rigorous examination of
      demographics and clinical indications. The PM Registry showed stable
      electrocardiographic and symptom indications, with an important prevalence of
      dual-chamber pacing. The use of CRT-PM regards a very limited number of patients.
      The ICD Registry documented a constant increase in prophylactic and biventricular
      ICD use, reflecting a favorable adherence to trials and guidelines in clinical
      practice.

PMID- 24326643
TI  - Palm vitamin eprotects bone against dexamethasone-induced osteoporosis in male
      rats.
AB  - The aim of this study was to determine the effects of palm oil-derived vitamin E
      on glucocorticoid-induced osteoporosis. Three-month old male Wistar rats were
      adrenalectomised to remove circulating glucocorticoids. The animals were then
      administered with Dexamethasone 120 ug/kg body weight/day. Treatment with palm
      vitamin E 60 mg/kg body weight/day was given simultaneously. The results showed
      that palm vitamin E prevented the loss in regional and whole body bone mineral
      density seen in the Dexamethasone treated animals. Palm vitamin E improved
      femoral length and calcium content in the Dexamethasone treated animals. The
      results confirmed that palm oil-derived vitamin E was effective in preventing
      glucocorticoid-induced osteoporosis. 

PMID- 24326644
TI  - Patients' desire for information about anaesthesia: a survey in a teaching
      hospital.
AB  - The aim of this study was to investigate the attitudes and desire of Malaysian
      patients for information about anaesthesia and compare the result to that of
      other similar studies in other countries namely Scotland, Canada, Australia and
      denMark. Two hundred and forty patients undergoing elective surgery were asked to
      complete a preoperative quentionnaire examining their desire for information
      relating to anaesthesia. As in all countries compared, most Malaysian patients
      were interested to know the time they could start to mobilize from the bed and
      the time to commence normal oral intake postoperatively. Information related to
      postoperative pain and pain relief was also highly desired. However, patients
      showed less interest towards information about perioperative anaesthetic or
      surgical procedures and drug used. Unlike Australian patients, the Malaysian
      patients showed less interest about perioperative complications. As in other
      countries, patients under the age of 50 years had a greater desire for
      information than those who were older. However there was no difference in desire
      for information between male and female patients. Patients who have had previous
      anaesthesia would ask more information compared to those who had none. 

PMID- 24326645
TI  - Bleeding peptic ulcer: experience with endoscopic therapy.
AB  - Bleeding is a serious complication of peptic ulcer and mortality rate has
      remained at approximately 10% or more. Traditionally surgeons selected patients
      who were at significant risk of continued or re-bleeding and advocated early
      surgery. However, patients with bleeding peptic ulcers are generally elderly with
      coexisting medical illness and surgery results in significant morbidity and
      mortality. In the last decade, endoscopic haemostatic therapy has been effective
      in arresting the bleeding with surgical option considered only after endoscopic
      treatment has failed. We report the outcome of 196 patients who were
      endoscopically diagnosed to have bleeding from peptic ulcers. One hundred and
      thirty patients were to have active bleeding or recent bleed from the ulcer.
      Endoscopic adrenaline injection therapy was used in 53 patients who had active
      bleeding ulcers and another 77 patients with endoscopic evidence of recent bleed.
      The injection therapy was successfully in 127 (97.7%) patients. The treatment
      failed in three patients and they underwent urgent surgery. Re-bleeding occurred
      in 26 (20.5%) patients and endoscopic adrenaline therapy was repeated in these
      cases. Haemostatic was achieved in 19 patients, however 7 patients continued to
      bleed and required surgery. There were 3 deaths, principally from advanced age
      and coexisting medical illness. Endoscopic therapy for bleeding peptic ulcers is
      simply to apply, safe and effective. In cases of re-bleeding after initial
      endoscopic hemostasis, re-treatment is a preferable alternative to surgery. The
      role of surgery is limited to bleeding that is refractory or inaccessible to
      endoscopic control. 

PMID- 24326646
TI  - A study of proliferating cell nuclear antigen expression in benign, borderline
      and malignant epithelial tumours of ovary.
AB  - Borderline epithelial tumours or low malignant potential epithelial tumours of
      ovary have a better prognosis and hence it is important to distinguish this group
      from their malignant counterparts. Several studies were done correlate the growth
      rates of tumours with nuclear proteins that are expressed in proliferating cells.
      Immunohistochemical stains with monoclonal antibodies against proliferating cell
      nuclear antigen (PCNA) were used on 51 archival epithelial tumours of ovary. The
      percentage of PCNA reactivity showed means of 1.1%, 2.3% and 27.7% with benign,
      borderline tumours and malignant epithelial tumours of ovary. respectively. The %
      PCNA reactivity was found to be significantly different amongst the three group
      (p<0.001). Thus , PCNA reactivity can help to differentiate borderline tumours
      from malignant epithelial tumours of ovary. This is critical when light
      microscopic appearances are equivocal and therapeutic management is dependent on
      the diagnosis. 

PMID- 24326647
TI  - Reliability and Validity of the Malay Version of the General Health Questionnaire
      (GHQ - 12) Among Urological Patients.
AB  - The aim of the study was to validate the Malay version of the General
      Quentionnaire (GHQ-12) in patients with psychiatric morbidity secondary to
      urological disorder. Validity and reliability were studied in patients with lower
      urinary tract symptoms (LUTS) and patients without LUTS. Internal consistency was
      excellent. A high degree of internal consistency was observed for each of the 12
      items and total scores (Cronbach's alpha value = 0.50 and higher and 0.65
      respectively. Test-retest correlation coefficient for the 12 items scores was
      highly significant. Intraclass correlation coefficient was high (ICC=0.47 and
      above). A significant level between baseline and post-treatment scores were
      observed across 3 items in the surgical group. The Mal-GHQ-12 is a suitable,
      reliable, valid and sensitive to clinical change in the Malaysian population. 

PMID- 24326648
TI  - Progesterone Profiles in Pregnant, Non-Pregnant, Natural and Stimulated IVF
      Cycles with and Without Luteal Support.
AB  - OBJECTIVES: (1) To describe the progesterone profiles following pituitary down
      regulation in stimulated IVF cycles with the use of GnRH-a (2) To assess the
      impact of progesterone supplement and pregnancy on the subsequent luteal phase.
      STUDY DESIGN: A prospective observational study performed in a specialist
      infertility clinic based at a tertiary centre in the north of England. Subjects
      were divided into cohorts depending on their treatment (natural or stimulated IVF
      cycles), the type of luteal support (nil or Progesterone) and eventual outcome
      (successful pregnancy or failure to conceive). Saliva Progesterone concentrations
      were the only measuring outcome. RESULTS: Natural versus stimulated cycle (SIVF);
      As expected saliva progesterone concentrations were significantly higher in
      subjects undergoing SIVF than in the natural cycle from day 1 to day 6 of the
      cycle (P<0.001) but thereafter stimulated cycle concentrations declined
      prematurely to fall below those of the natural cycle group by day 7, becoming
      significantly lower than natural cycle concentrations by days 9 and 10 (P<0.01).
      With and without progesterone supplementation; Saliva progesterone concentrations
      in subjects undergoing NIVF and receiving progesterone supplement were 2.5-3
      times greater than those concentrations seen in the unsupplementated natural
      cycle (P<0.001). Similarly in the SIVF-Progesterone supplemented group, saliva
      concentrations remained significantly higher (P<0.001) than in the unsupplemented
      cycle throughout luteal phase. Despite this, luteal supplementation did not
      prevent nor reverse the acute mid luteal (day 7) decline in progesterone seen in
      all stimulated cycles. CONCLUSION: Luteal phase following pituitary down
      regulation is grossly abnormal. The timing and degree of luteal support routinely
      provided following stimulated IVF is not effective in 'correcting' the
      progesterone profile.

PMID- 24326649
TI  - Breastfeeding practices among mothers in an urban polyclinic.
AB  - A cross sectional descriptive study on breast feeding practices in an urban
      clinic was conducted among 136 mothers aged between 21-49 years who were
      interviewed using a questionnaire. Malays constituted 61% of the respondents,
      Chinese 22.8% and Indians 16.2%. Mojority of these were working mothers and
      although the initiation of breastfeeding was high (99.3%), exclusive
      breastfeeding was only 12.5%. A large proportion (33.8%) dtopped prior to 3
      months. Majority of the Chinese mothers (61.3%) stipped before 3 months as
      compared to the Indian (40.9%) and Malay (21.7%) mothers (p<0.001). Mean age of
      introducing complementary foods at 3 months is below the accepted age of 4 to 6
      months for weaning. Ever-breast feeding rate is high in this urban setting but
      more efforts are needed to effect a higher rate of exclusive breastfeeding and
      longer duration of breastfeeding. 

PMID- 24326650
TI  - Diabetes Mellitus in a Malaysian Teaching Hospital: Prevalence of Diabetes
      Mellitus and Frequency of Testing for Hypercholesterolaemia, Proteinuria and
      HbAlc.
AB  - We examined the prevalence of diabetes among inpatients in our hospital, the
      relationship of the diagnoses on admission to diabetes, and the frequency of
      testing for HbA1c as a marker of long-term glycaemic control, proteinuria, and
      hypercholesterolaemia. In addition, patients with raised laboratory plasma
      glucose without a know history of diabetes mellitus, were studied to see if these
      had been further evaluation. The overall prevalence of diabetes in our hospital
      was 25.% with the highest prevalence found (37.8%) on medical wards. 10.5% of
      admissions were due directly to diabetes and a further 58.9% of patients were
      admitted with illness which were significant related to diabetes. Overall testing
      rates for HbA31c, proteinuria, and hypercholesterolaemia were less than ideal
      (51.6, 73.4 and 45.% respectively). Less than 50% of patients without previously
      diagnosed diabetes but with high plasma glucose values had further evaluation for
      diabetes. In conclusion, this study has detected a high overall prevalence of
      diabetes among inpatients in an urban Malaysian hospital. Rates of testing for
      HbA51c, proteinuria, and hypercholesterolaemia, are disappointingly low, as is
      further evaluation of patients without known diabetes, but with elevated glucose
      values. More effective measures to improve the delivery of inpatient diabetes
      care are needed. 

PMID- 24326651
TI  - Serum Eosinophilic Cationic Protein (ECP) in Asthmatic Malaysian Children.
AB  - Eosinophilic inflammation in the airways is important in the pathogenesis of
      childhood asthma. Serum eosinophilic cationic protein (ECP), a marker of
      eosinophil activation was measured in 20 asthmatic children and 19 non-asthmatic
      controls. There was no difference in the socio-demography, passive smoke
      exposure, urinary cotinine levels and family history of asthma between the 2
      groups. The median serum ECP in asthmatic children was 27.0 mcg/L (IQ1 8.8, IQ3
      59.0); which was higher than in non-asthmatic controls [5.9 mcg/L (IQ1 3.0, IQ3
      11.9), p=0.002]. An elevated serum ECP level can be helpful as supportive
      evidence in the diagnosis of bronchial asthma in Malaysia children. 

PMID- 24326652
TI  - Is arthoscopy of the shoulder safe - a study/perspective on arthroscopic
      subracromial decompression.
AB  - Fourteen fit and healthy patients underwent arthroscopic subacromial
      decompression (ASD) of shoulder for rotator cuff impingement. Their blood
      chemistry was analysed pre-operatively, 24 hours post-operatively and 2-3 weeks
      post-operatively. Levels of haematocrit, sodium, potassium, creatinine and urea
      were measured. The blood chemistry returned almost to the pre-operative level at
      2-3 weeks post-operatively. There was no statistically significant differences
      found. This study concludes that arthroscopic subacromial decompression is a safe
      technique when considering the blood parameters despite the haemodilution seen in
      all patients. 

PMID- 24326653
TI  - An unusual case of metformin associated lactic acidosis.
AB  - Metformin Associated Lactic Acidosis (MALA) is a rare, but serious complications
      of Type 2 diabetes mellitus treatment with a mortality rate of around 50%. It
      most commonly occurs in the setting of hepatic, cardiac or renal insufficiency.
      We report the case of an elderly female with MALA and concomitant starvation
      ketosis in the absence of any known risk factor, who went undiagnosed for a
      period of at least a month and made a complete recovery in the hospital. 

PMID- 24326654
TI  - Waldenstrom's Macroglobulinaemia Presenting as Demyelinating
      Polyradiculoneuropathy.
AB  - Patients (particularly elderly) undergoing evaluation for peripheral neuropathy
      of unknown cause should be screened for the presence of a monoclonal protein (M
      protein). The association of a neuropathy and a paraproteinaemia such as
      Waldenstrom's Macroglobulinaemia (WM) is not uncommon with the former antedating
      the haematologic symptoms by several years. Response to treatment has varied from
      good to very poor. We describe a case of WM presenting as a subacute
      demyelinating peripheral neuropathy. There was prompt resolution of the
      neuropathy with intravenous immunoglobulin therapy. Subsequent treatment with
      cyclophosphamide and plasmapheresis resulted in complete clinical remission with
      no further neurological relapses. 

PMID- 24326655
TI  - Visual disturbances with clomiphene.
AB  - Clomiphene is a widely prescribed drug for the treatment of infertility. Visual
      symptoms that occur as a side effect of this drug are uncommon. Some doctors may
      neglect to mention this side effect when prescribing clomiphene. Thus these
      visual disturbances can be very alarming to the patient and may also pose a
      hazard if the patient is doing activities such as driving or operating machinery.
      The patient should be told to stop taking clomiphene and ophthalmologic
      evaluation should be performed. Although visual disturbances generally cease on
      stopping clomiphene, some women may experience persistent visual disturbances. 

PMID- 24326656
TI  - Cervical sympathetic schwannoma simulating a thyroid nodule.
AB  - Schwannomas are rare tumours arising from peripheral nerve linings. A case of a
      schwannoma arising from cervical sympathetic chain is presented. The clinical
      presentation was that of a right solitary thyroid nodule. Intra-operatively, a 3
      x 3 cm encapsulated lesion was seen arising posterior to the vagas nerve and
      attached to the cervical sympathetic trunk. The lesion was excised together with
      part of the nerve. Post-operatively, the patient developed Horner's syndrome that
      persisted. Unitil 2000, less that 50 cased of cervical sympathetic schwannoma
      have been described in the Englidh literature. A brief description of the
      pathology, presentation, diagnosis and treatment of this condition is presented. 

PMID- 24326657
TI  - An unusual cause of efferent loop obstruction.
AB  - A patient who presented with massive upper gastrointestinal hemorrhage underwent
      a Billroth II partial gastrectomy. He developed efferent loop obstruction due to
      a retained abdominal drain. Relaparotomy for removal of drain was performed.
      Retained drains are known complications but rarely, it is cause of efferent loop
      obstruction. 

PMID- 24326658
TI  - "Cauliflower ears" in a patient with anterior uveitis.
AB  - "Cauliflower Ears" describes the appearance of swelling of the auricular
      cartilage resulting in gross distortion of the auricle. The underlying pathology
      is inflammation of the auricular cartilage. We report a case of a patient who
      presented to the ophthalmology clinic with an ocular inflammation, whose
      subsequent diagnosis of replapsing polychondritis was clinched with the finding
      of "Cauliflower Ears". This case emphasizes the importance of an appropriate
      general examination of ophthalmic patients for early diagnosis and prompt
      institution of medical treatment, which may prevent life-threatening
      complications to the patient. 

PMID- 24326659
TI  - Superior masenteric vein thrombosis.
AB  - A 43 year-old woman presented with severe non-specific abdominal pain of 1-week
      duration. She was on oral contraceptive pills for the past 6 years. Clinically
      patient appeared ill with no specific abnormal physical sign. Moderate amount of
      free fluid in the peritoneal cavity on ultrasound prompted an urgent abdominal
      computed tomography (CT) scan, which revealed thrombosis of the superior
      mesenteric vein. Further investigations revealed a hypercoagulable state with
      protein C deficiency. Patient responded well to anticoagulation and supportive
      therapy. One month later patient readmitted with vomiting and signs of intestinal
      obstruction. Barium study revealed a moderately long tight stricture at mid
      jejunum with proximal dilation. A by-pass surgery was carried out. She was well
      at 3 months follow-up. 

PMID- 24326660
TI  - Angiosarcoma of the liver.
AB  - A 47-years-old Malay man presented with unremitting epigastric pain and loss
      weight for 3 months. At laparotomy, a large tumour mas was found in the liver and
      a few small nodules in the spleen. Histopathological examination revealed a
      hepatic angiosarcoma with metastsis to the spleen. He had exposure to formic acid
      fumes for more than 23 years in his work as a rubber tapper. The various chemical
      carcinogens that are implicated in this type of tumour are discussed. The
      possiblity of an association between formic acid fumes and development of
      angiosarcoma in the liver is highlighted. 

PMID- 24326661
TI  - A case of tuberculosis of the thyroid gland.
AB  - We report a case of tuberculosis of the thyroid gland associated with mediastinal
      lymphadenitis in a 30 years-old male, who presented with dysphagia and a mid line
      anterior neck swelling. Fine needle aspiration was positive for acid fast
      bacilli. He made an uneventful recovery with antituberculous drugs. Although
      seldom observed, tuberculosis should be kept in mind in te differential diagnisis
      of nodular lesions of the thyroid. 

PMID- 24326662
TI  - Adult acute epiglottitis.
AB  - Acute epiglotiitis is a disease of rapid onset and progression of symptoms and
      has been well described in children. The importance of being aware of this
      diagnosis is to prevent an acute upper airway obstruction that can be potentially
      fatal. Here we describe two cases of adult acute epiglottitis where the patients
      had severe symptoms of sorethroat but a normal looking oropharynx. 

PMID- 24326663
TI  - Re-emergence of dengue 4 virus.

PMID- 24326664
TI  - Avoiding Osteoradionecrosis - The Dental Surgeo's Nightmaren.
AB  - Osteoradionecrosis is a severe debilitating complication; it may occur from
      radiotherapy to the bones. It is a dental surgeon's nightmare as it may be long
      standing and difficult to manage. Osteoradionecrosis is characterised by hypoxia,
      hypocellularity and hypovascularity of the affected tissue. This paper reviews
      osteoradionecrosis in relation to dental treatment. 

PMID- 24326665
TI  - Involvement of cytochromes p450 in drug-drug interactions: an overview.
AB  - Drug interactions can cause iatrogenic disease. If concurrent medications are
      taken, the potential exists for a drug interaction to occur. Renewed interest in
      the topic interactions has been generated by the fatal interactions involving non
      sedating histamine H-1 antagonists and the recent intriduction of two therapeutic
      agents, the selective serotonin reuptake inhibitors (SSRIs) and HIV protease
      inhibitors, for the treatment of depression and AIDS, respectively. These three
      therapeutic agents have been implicated in clinically significant drug
      interactions. The consequences of these interactions vary in clinical
      significance, extent, and effect. Some interactions are theoretical whereas
      others may lead to severe iatrogenic adverse experiences including lethal
      consequences.The purpose of this review is to alert the medical practioner to
      potential drug interactions that may occur when these drugs are prescribed to
      patients. The pharmacological basis and clinical signficance of these
      interactions are reviewed. The pharmacological mechanisms underlying these
      interactions are illustrative of those that may be involved for many other
      medications. Doctors should be aware of the potential pitfall that may occur when
      certain groups of drugs are prescribed with concurrent medications. 

PMID- 24326667
TI  - Patients are at risk because doctors don't know how much IV fluid they need, NICE
      says.

PMID- 24326668
TI  - Bioengineering murine mastocytoma cells to produce anticoagulant heparin.
AB  - Heparin (HP), an important anticoagulant polysaccharide, is produced in a complex
      biosynthetic pathway in connective tissue-type mast cells. Both the structure and
      size of HP are critical factors determining the anticoagulation activity. A
      murine mastocytoma (MST) cell line was used as a model system to gain insight
      into this pathway. As reported, MST cells produce a highly sulfated HP-like
      polysaccharide that lacks anticoagulant activity (Montgomery RI, Lidholt K, Flay
      NW, Liang J, Vertel B, Lindahl U, Esko JD. 1992. Stable heparin-producing cell
      lines derived from the Furth murine mastocytoma. Proc Natl Acad Sci USA 89:11327
      11331). Here, we show that transfection of MST cells with a retroviral vector
      containing heparan sulfate 3-O-sulfotransferase-1 (Hs3st1) restores anticoagulant
      activity. The MST lines express N-acetylglucosamine N-deacetylase/N
      sulfotransferase-1, uronosyl 2-O-sulfotransferase and glucosaminyl 6-O
      sulfotransferase-1, which are sufficient to make the highly sulfated HP.
      Overexpression of Hs3st1 in MST-10H cells resulted in a change in the composition
      of heparan sulfate (HS)/HP and CS/dermatan sulfate (DS) glycosaminoglycans. The
      cell-associated HS/HP closely resembles HP with 3-O-sulfo group-containing
      glucosamine residues and shows anticoagulant activity. This study contributes
      toward a better understanding of the HP biosynthetic pathway with the goal of
      providing tools to better control the biosynthesis of HP chains with different
      structures and activities. 

PMID- 24326669
TI  - African-American breast cancer survivors participating in a breast cancer support
      group: translating research into practice.
AB  - Despite an overall decline in mortality, breast cancer is the most commonly
      diagnosed cancer and the second most common cause of cancer death among African
      American women. As such, clinicians should prepare to address the unique
      sociocultural and psychological concerns encountered by African-American women
      breast cancer survivors. The objective of this study is to examine, using
      qualitative methods, the main coping facilitators used by African-American women
      as they transition across the cancer continuum. The identification of these
      facilitators was then aligned with culturally sensitive interventions most useful
      with women coping with cancer along the cancer continuum. This was a secondary
      analysis of 20 videotaped stories of African-American breast cancer survivors
      collected as a part of the Washington University Center for Excellence in Cancer
      Communications project. The interview began with a discussion of how the survivor
      first became aware she had breast cancer, followed by a series of open-ended
      probes used to explore the following themes: coping, relationships, health care
      system experiences, follow-up care, and quality of life living with breast
      cancer. Survivors discussed their experiences and advice for targeting needs at
      each cancer stage from screening to diagnosis, treatment, and then survivorship.
      Survivor narratives point to key evidence-based clinical intervention strategies
      at each stage of the cancer trajectory. This study found that survivors see a
      cyclical cancer course, whereby African-American breast cancer survivors serve an
      important role in the lives of unscreened women, newly diagnosed women, and women
      in treatment. 

PMID- 24326671
TI  - Functional connectivity changes within specific networks parallel the clinical
      evolution of multiple sclerosis.
AB  - BACKGROUND: In multiple sclerosis (MS), the location of focal lesions does not
      always correlate with clinical symptoms, suggesting disconnection as a major
      pathophysiological mechanism. Resting-state (RS) functional magnetic resonance
      imaging (fMRI) is believed to reflect brain functional connectivity (FC) within
      specific neuronal networks. OBJECTIVE: RS-fMRI was used to investigate changes in
      FC within two critical networks for the understanding of MS disabilities, namely,
      the sensory-motor network (SMN) and the default-mode network (DMN), respectively,
      implicated in sensory-motor and cognitive functions. METHODS: Thirty-four
      relapsing-remitting (RR), 14 secondary progressive (SP) MS patients and 25
      healthy controls underwent MRI at 3T, including conventional images, T1-weighted
      volumes, and RS-fMRI sequences. Independent component analysis (ICA) was employed
      to extract maps of the relevant RS networks for every participant. Group analyses
      were performed to assess changes in FC within the SMN and DMN in the two MS
      phenotypes. RESULTS: Increased FC was found in both networks of MS patients.
      Interestingly, specific changes in either direction were observed also between RR
      and SP MS groups. CONCLUSIONS: FC changes seem to parallel patients' clinical
      state and capability of compensating for the severity of clinical/cognitive
      disabilities.

PMID- 24326670
TI  - A wheat allene oxide cyclase gene enhances salinity tolerance via jasmonate
      signaling.
AB  - One of the two branches of the alpha-linolenic acid metabolism pathway is
      catalyzed by 12-oxo-phytodienoic acid reductase I, and the other is involved in
      jasmonic acid (JA) synthesis. The former is known to be active in the response to
      salinity tolerance in wheat (Triticum aestivum), but the participation of the
      latter in this response has not been established as yet. Here, the salinity
      responsive bread wheat gene TaAOC1, which encodes an allene oxide cyclase
      involved in the alpha-linolenic acid metabolism pathway, was constitutively
      expressed in both bread wheat and Arabidopsis (Arabidopsis thaliana). In both
      species, transgenic lines exhibited an enhanced level of tolerance to salinity.
      The transgenic plants accumulated a higher content of JA and developed shorter
      roots. Both the shortened roots and the salinity tolerance were abolished in a
      background lacking a functional AtMYC2, a key component of the JA and abscisic
      acid signaling pathway, but were still expressed in a background deficient with
      respect to abscisic acid synthesis. We provide the first evidence, to our
      knowledge, suggesting that JA is also involved in the plant salinity response and
      that the alpha-linolenic acid metabolism pathway has a regulatory role over this
      response. 

PMID- 24326672
TI  - Milder multiple sclerosis course in patients with concomitant inflammatory bowel
      disease.
AB  - An association between multiple sclerosis (MS) and inflammatory bowel disease
      (IBD) has been suggested. The purpose of this study was to compare the disease
      course of patients with both MS and IBD with that of patients with isolated MS or
      isolated IBD. Sixty-six MS-IBD patients were identified and were matched with 251
      isolated MS and 257 isolated IBD controls. Main outcomes were scores using the
      Expanded Disability Status Scale (EDSS) in MS and extent of disease extension in
      IBD at last clinical evaluation. After a median 12 years of disease duration, the
      median EDSS and the percentages of patients reaching an EDSS of 3.0 and 4.0 were
      significantly lower in MS-IBD patients than in controls. MS had no impact on IBD.
      MS course appears to be milder in patients with concomitant IBD.

PMID- 24326673
TI  - Multiple sclerosis in Isfahan, Iran: an update.

PMID- 24326674
TI  - High-resolution, high-speed, three-dimensional video imaging with digital fringe
      projection techniques.
AB  - Digital fringe projection (DFP) techniques provide dense 3D measurements of
      dynamically changing surfaces. Like the human eyes and brain, DFP uses
      triangulation between matching points in two views of the same scene at different
      angles to compute depth. However, unlike a stereo-based method, DFP uses a
      digital video projector to replace one of the cameras(1). The projector rapidly
      projects a known sinusoidal pattern onto the subject, and the surface of the
      subject distorts these patterns in the camera's field of view. Three distorted
      patterns (fringe images) from the camera can be used to compute the depth using
      triangulation. Unlike other 3D measurement methods, DFP techniques lead to
      systems that tend to be faster, lower in equipment cost, more flexible, and
      easier to develop. DFP systems can also achieve the same measurement resolution
      as the camera. For this reason, DFP and other digital structured light techniques
      have recently been the focus of intense research (as summarized in(1-5)). Taking
      advantage of DFP, the graphics processing unit, and optimized algorithms, we have
      developed a system capable of 30 Hz 3D video data acquisition, reconstruction,
      and display for over 300,000 measurement points per frame(6,7). Binary defocusing
      DFP methods can achieve even greater speeds(8). Diverse applications can benefit
      from DFP techniques. Our collaborators have used our systems for facial function
      analysis(9), facial animation(10), cardiac mechanics studies(11), and fluid
      surface measurements, but many other potential applications exist. This video
      will teach the fundamentals of DFP techniques and illustrate the design and
      operation of a binary defocusing DFP system. 

PMID- 24326675
TI  - Six-step framework for ethical decision making.
AB  - The expectation, from the ethos of medicine and society, is that a practitioner
      should make the correct ethical decision in the clinical setting. Yet there is
      little help for them as to a process for making ethical decisions. A structured
      six-step framework may assist. It is not an algorithm to arrive at a determinate
      answer in all situations and ethical issues but instead offers a process that
      indicates the most relevant information and biomedical considerations a
      practitioner needs to be aware of and helps to make ethics issues more
      manageable. The issues practitioners face are complex and resistant to reduction;
      it is hubris to pretend otherwise. Yet, the difficulty of these issues warrants
      practitioners relying on a framework to guide them in the process of making
      ethical decisions. 

PMID- 24326676
TI  - Detrimental effects of metronidazole on selected innate immunological indicators
      in common carp (Cyprinus carpio L.).
AB  - The widely used antibiotic metronidazole (MTZ) was investigated for its toxic
      effects on the innate immunity in common carp (Cyprinus carpio L.). The fish were
      exposed to MTZ at nominal concentrations of 0.1, 0.5, and 2.5 mg L(-1) in water
      for 30 days, followed by a 5-days of cleanout period, after which certain innate
      immunity parameters were measured. The results showed that under the tested
      concentrations, MTZ-exposed fish exhibited decline in several humoral and
      cellular parameters, including complement activity, lysozyme activity,
      bactericidal activity, total serum protein levels, total WBC count, and the
      respiratory burst activity of kidney leukocytes. Except for total serum proteins,
      all of these parameters showed a significant difference in the 2.5 mg L(-1) MTZ
      group compared to control group (p < 0.05). The results clearly support the
      contention that MTZ suppresses the innate immunity of common carp.

PMID- 24326677
TI  - Nutritional quality and safety related to trace element content in fish from
      Tyrrhenian Sea.
AB  - This study analyzed for the detection of the following trace elements: As, Cd,
      Cu, Hg, Pb, Se, Zn, in muscle of four widely traded and consumed marine fish
      species (Mullus surmuletus L., Merluccius merluccius L., Micromesistius poutassou
      (Risso, 1827), Scomber scombrus L.) selected for their wide trade and
      consumption. Mean concentrations found in fish muscle, irrespective of species,
      ranged from 3.61 to 105.49 (As); 0.01-0.08 (Cd); 0.74-4.71 (Cu); 0.09-1.10 (Hg);
      0.02-0.58 (Pb); 0.30-2.88 (Se); 11.56-73.37 (Zn) mg/kg wet weight. As, Hg, Cu and
      Se concentrations showed a significant difference (p < 0.01) among the analyzed
      species in winter and in summer. Cd exhibited a significant difference (p < 0.01)
      only in summer. The maximum levels set for Hg, Cd and Pb by European Regulation
      No 1881/2006 were exceeded by 5 (8.9%), 1 (1.8%) and 4 (7.1%) samples,
      respectively. In particular the species exceeding the legal limits were red
      mullet for Cd and Pb, Atlantic mackerel and blue whiting for Hg and Pb.

PMID- 24326678
TI  - Acetaldehyde detoxification using resting cells of recombinant Escherichia coli
      overexpressing acetaldehyde dehydrogenase.
AB  - Acetaldehyde dehydrogenase (E.C. 1.2.1.10) plays a key role in the acetaldehyde
      detoxification. The recombinant Escherichia coli cells producing acetaldehyde
      dehydrogenase (ist-ALDH) were applied as whole-cell biocatalysts for
      biodegradation of acetaldehyde. Response surface methodology (RSM) was employed
      to enhance the production of recombinant ist-ALDH. Under the optimum culture
      conditions containing 20.68 h post-induction time, 126.75 mL medium volume and 3
      % (v/v) inoculum level, the maximum ist-ALDH activity reached 496.65 +/- 0.81
      U/mL, resulting in 12.5-fold increment after optimization. Furthermore, the
      optimum temperature and pH for the catalytic activity of wet cells were 40 
      degrees C and pH 9.5, respectively. The biocatalytic activity was improved 80 %
      by permeabilizing the recombinant cells with 0.075 % (v/v) Triton X-100. When
      using 2 mmol/L NAD(+) as coenzyme, the permeabilized cells could catalyze 98 % of
      acetaldehyde within 15 min. The results indicated that the recombinant E. coli
      with high productivity of ist-ALDH might be highly efficient and easy-to-make
      biocatalysts for acetaldehyde detoxification.

PMID- 24326679
TI  - miRNAs: a new method for erythroid differentiation of hematopoietic stem cells
      without the presence of growth factors.
AB  - Micro RNAs (miRNAs) are a novel class of non-coding regulatory RNA molecules that
      contribute to post-transcriptional gene regulation. Recent studies have
      demonstrated that specific miRNAs such as miR-150, miR-154, and miR-451 have key
      roles in erythropoiesis. To date, stimulatory cytokines are considered as unique
      effectors for in vitro differentiation of HSCs to erythropoietic lineage.
      However, the use of these factors is not cost-effective for clinical applications
      and therapeutic strategies. Here, we present a novel and cost-effective strategy
      in which miRNAs expression modulation promotes erythroid differentiation in HSCs
      in the absence of any extrinsic factors. Thus, CD133(+) hematopoietic stem cells
      purified from human umbilical cord blood were treated with pre-miR-451 containing
      lentiviruses, anti-miR-150 and anti-miR-154 in the absence of growth factors and
      cytokines. Obtained results indicated that miR-451 upregulation and miR-150
      downregulation have positive effect on GATA-1, FOG-1, and EKLF, CD71 and CD235a
      genes expression and induce hemoglobinization efficiently. However,
      downregulation of miR-154 had no effect on erythropoiesis indexes compared to
      that observed in the control group. In conclusion, the data presented here for
      the first time demonstrate that expression modulation of miR-451 and miR-150
      could be an efficient alternative to stimulatory cytokines for CD133(+)
      differentiation into erythroid lineage. Modulation of erythropoiesis in stem
      cells via miRNA holds promising potential for vascular tissue engineering and
      regenerative medicine applications. 

PMID- 24326680
TI  - Aptamer-based biosensor for detection of phenylalanine at physiological pH.
AB  - A simple, sensitive aptamer-based biosensor for the detection of phenylalanine is
      developed using the electrochemical transduction method. For this proposed
      aptasensor, a 5-thiol-terminated aptamer is covalently attached onto a gold
      electrode. At the first time, the electrode was evaluated as an electrochemical
      aptasensor for determination of phenylalanine in aqueous solutions. This sensor
      was tested in a Tris-HCl buffer with physiological pH = 7.4 by cyclic voltammetry
      and differential pulse voltammetry. The detection limit and sensitivity of the
      modified electrode toward phenylalanine were estimated to be 1 nM (S/N = 3) and
      0.367 MUA nM(-1), respectively. The linear range of the signal was observed
      between 1 and 10 nM of phenylalanine with 0.9914 correlation factor. The herein
      described approach is expected to promote the exploitation of aptamer-based
      biosensors for protein assays in biochemical and biomedical studies.

PMID- 24326681
TI  - Microbiological transformation of L-tyrosine to L-dopa from methanol pretreated
      biomass of a novel Coriolus versicolor under submerged culture.
AB  - The present study is concerned with the microbiological transformation of L
      tyrosine to L-dopa by a newly isolated turkey tail mushroom Coriolus versicolor
      DOB-4. As tyrosinase (catechol oxidase, EC 1.10.3.1) is an extracellular enzyme,
      therefore biomass was used as an enzyme source in the reaction mixture. Biomass
      particles were pretreated with methanol and oven dried at 105  degrees C for 2 h.
      The optimal L-dopa production was achieved when 1.5 mg/ml L-tyrosine was used as
      the basal substrate. Thin layer chromatography and high-performance liquid
      chromatography analysis depicted that citric acid supports higher substrate
      conversion and product formation rates. A noticeable enhancement was observed
      when process parameters viz. L-tyrosine concentration (1.5 mg/ml), citric acid
      (1.5 mg/ml), time of incubation (50 min), and reaction temperature (60  degrees
      C) were optimized using Plackett-Burman design. The maximum production of L-dopa
      was found to be 0.872 mg/ml with L-tyrosine consumption of 1.002 mg/ml. The model
      terms were found highly significant (HS, p <= 0.05), suggesting the potential
      commercial utility of the culture (df = 3, LSD = 0.342).

PMID- 24326682
TI  - Immobilization of xylanase on poly (ethylene glycol) methyl ether 5000 and its
      self-extractive bioconversion for the production of xylo-oligosaccharides.
AB  - Endo-beta-1,4-xylanase derived from Trichoderma reesei was covalently immobilized
      on poly (ethylene glycol) methyl ether 5000 (mPEG5000), and the resulting
      immobilized enzyme had a residual activity of 72.4 % with 82.9 % of PEGylated
      amino groups. Compared with the free enzyme, the immobilized xylanase was stable
      at pH values in the range of 4.0-6.0 and temperatures in the range of 50-65 
      degrees C. A self-extractive bioconversion system composed of immobilized
      xylanase, mPEG5000, and sodium citrate was used to produce xylo-oligosaccharides
      and provided a better distribution of the xylo-oligosaccharides than the free
      enzyme. Furthermore, the immobilized xylanase could be effectively recovered in
      situ following the hydrolysis reaction.

PMID- 24326684
TI  - An MDS xenograft model utilizing a patient-derived cell line.

PMID- 24326683
TI  - GAS6 expression identifies high-risk adult AML patients: potential implications
      for therapy.
AB  - Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor
      tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the
      prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in
      270 adults (n=71 aged<60 years; n=199 aged ?60 years) with de novo
      cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6
      (GAS6+), especially those aged ?60 years, more often failed to achieve a complete
      remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS)
      and overall (OS) survival than patients without GAS6 expression (GAS6-). After
      adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02),
      shorter DFS (P=0.004) and OS (P=0.04). To gain further biological insights, we
      derived a GAS6-associated gene-expression signature (P<0.001) that in GAS6+
      patients included overexpressed BAALC and MN1, known to confer adverse prognosis
      in CN-AML, and overexpressed CXCL12, encoding stromal cell-derived factor, and
      its receptor genes, chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. This
      study reports for the first time that GAS6 expression is an adverse prognostic
      marker in CN-AML. Although GAS6 decoy receptors are not yet available in the
      clinic for GAS6+ CN-AML therapy, potential alternative therapies targeting GAS6+
      associated pathways, for example, CXCR4 antagonists, may be considered for GAS6+
      patients to sensitize them to chemotherapy. 

PMID- 24326685
TI  - Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and
      increasing BDNF levels.
AB  - Astaxanthin (AST) is a carotenoid pigment which possesses potent antioxidative,
      anti-inflammatory, and neuroprotective properties. The aim of this study was to
      investigate whether administration of AST had protective effects on D-galactose
      induced brain aging in rats, and further examined its protective mechanisms. The
      results showed that AST treatment significantly restored the activities of
      glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), and increased
      glutathione (GSH) contents and total antioxidant capacity (T-AOC), but decreased
      malondialdehyde (MDA), protein carbonylation and 8-hydroxy-2- deoxyguanosine (8
      OHdG) levels in the brains of aging rats. Furthermore, AST increased the ratio of
      Bcl-2/Bax, but decreased the expression of Cyclooxygenase-2 (COX-2) in the brains
      of aging rats. Additionally, AST ameliorated histopathological changes in the
      hippocampus and restored brain derived neurotrophic factor (BDNF) levels in both
      the brains and hippocampus of aging rats. These results suggested that AST could
      alleviate brain aging, which may be due to attenuating oxidative stress,
      ameliorating hippocampus damage, and upregulating BDNF expression.

PMID- 24326687
TI  - Memory: a boost for medical marijuana?

PMID- 24326689
TI  - Learning and memory: synapse remodelling extinguishes fear.

PMID- 24326686
TI  - Axon-soma communication in neuronal injury.
AB  - The extensive lengths of neuronal processes necessitate efficient mechanisms for
      communication with the cell body. Neuronal regeneration after nerve injury
      requires new transcription; thus, long-distance retrograde signalling from axonal
      lesion sites to the soma and nucleus is required. In recent years, considerable
      progress has been made in elucidating the mechanistic basis of this system. This
      has included the discovery of a priming role for early calcium waves;
      confirmation of central roles for mitogen-activated protein kinase signalling
      effectors, the importin family of nucleocytoplasmic transport factors and
      molecular motors such as dynein; and demonstration of the importance of local
      translation as a key regulatory mechanism. These recent findings provide a
      coherent mechanistic framework for axon-soma communication in the injured nerve
      and shed light on the integration of cytoplasmic and nuclear transport in all
      eukaryotic cells. 

PMID- 24326690
TI  - An elusive fulvene 1,7,11,24-C60(CF3)4 and its unusual reactivity.
AB  - The X-ray crystal structure of a trifluoromethylfullerene (TMF), 1,7,11,24
      C60(CF3)4, is reported for the first time. This elusive intermediate, while
      highly air stable as a solid, exhibits highly regioselective reactivity towards
      molecular oxygen in polar solvents, and only when exposed to light.

PMID- 24326688
TI  - Neurocriminology: implications for the punishment, prediction and prevention of
      criminal behaviour.
AB  - Criminal behaviour and violence are increasingly viewed as worldwide public
      health problems. A growing body of knowledge shows that criminal behaviour has a
      neurobiological basis, and this has intensified judicial interest in the
      potential application of neuroscience to criminal law. It also gives rise to
      important questions. What are the implications of such application for predicting
      future criminal behaviour and protecting society? Can it be used to prevent
      violence? And what are the implications for the way offenders are punished? 

PMID- 24326691
TI  - Parent vs burn-injured child self-report: contributions to a better understanding
      of anxiety levels.
AB  - Anxiety disorders are the most commonly reported form of mental health problem
      among youth, but they often go undiagnosed and untreated. This study examined the
      relationship between burn-injured youths' self-reported anxiety levels, as
      compared with their parent's perceptions of their child's emotional well-being.
      Burn-injured children were invited to voluntarily complete the Child Version of
      the 41-item survey, Screen for Child Anxiety Related Disorders, which consists of
      five anxiety subscales as well as a Total Anxiety Score. Parents were invited to
      complete the Parent Version. Sixty-three parent-child dyads, with girls (57%) and
      boys (43%), completed surveys. Mothers (73%) fathers (16%), and other caregivers
      (11%) participated. Youth mean age was 12.63 years and 60% reported visible burn
      scars. Matched-pairs t-tests were used to compare parent and child reports.
      Significantly lower mean scores were found between Screen for Child Anxiety
      Related Disorders Total Anxiety Score--Parent mean score of 10.52 vs the Youth
      mean score 21.06 (P<.001), as well as on all subscales including; panic
      disorder/somatic symptoms (P<.001), generalized anxiety disorder (P=.004), social
      anxiety disorder (separation anxiety (P<.001), and school avoidance (P<0.001).
      Results indicate that parents may be severely underestimating the psychological
      well-being of burn-injured youth. Findings emphasize the importance of a
      comprehensive approach in assessment for anxiety, involving the collection of
      feedback from both child and parent. Asking children for input into their
      psychological well-being is important. This study reinforces the need for a
      course of ongoing patient and parent education.

PMID- 24326692
TI  - Corticomotor excitability in Parkinson's disease during observation, imagery and
      imitation of action: effects of rehabilitation using wii fit and comparison to
      healthy controls.
AB  - BACKGROUND: Parkinson's disease (PD) is responsible for a progressive motor
      impairment. Wii Fit game represents an innovative treatment modality using
      external visual cueing, which can be used to help patients with PD in executing
      motor tasks and improving function. OBJECTIVES: The objectives of this study were
      (1) to compare lower limb corticomotor activation in subjects with and without PD
      during action observation (OBS), motor imagery (IMAG), and imitation (IMIT), and
      (2) to evaluate the effects of a 6-week training program using Wii Fit on
      corticomotor excitability during these 3 conditions. METHODS: Using transcranial
      magnetic stimulation, we assessed motor evoked potentials (MEPs) in Quadriceps
      Femoris (QF) and Soleus (SOL) muscles in 8 subjects with moderate PD (PD group)
      and 8 healthy subjects (HS group) before and after 6 weeks of training using Wii
      Fit during OBS, IMAG and IMIT of a mini-squat action. RESULTS: At baseline, PD
      showed significantly less MEPs in QF during OBS, IMAG and IMIT compared with HS.
      In SOL, MEPs were reduced in PD only during IMIT. Following training, PD
      increased QF MEPs during OBS, which was opposite to the decrease in QF MEPs noted
      in HS. During IMAG, increased MEPs were found only in PD for SOL. During IMIT,
      both groups significantly reduced MEPs in both QF and SOL. CONCLUSION: Subjects
      with PD may have improved their dual-task ability considering changes observed
      during OBS and IMIT. Visual cueing training using Wii Fit may provide an
      interesting rehabilitation method for PD.

PMID- 24326693
TI  - Droxidopa in patients with neurogenic orthostatic hypotension associated with
      Parkinson's disease (NOH306A).
AB  - BACKGROUND: Neurogenic orthostatic hypotension (nOH) is common in Parkinson's
      disease (PD), and represents a failure to generate norepinephrine responses
      appropriate for postural change. Droxidopa (L-threo-3,4-dihydroxyphenylserine) is
      an oral norepinephrine prodrug. OBJECTIVE: Interim analyses of the initial
      patients enrolled in a multicenter, randomized, double-blind, placebo-controlled
      phase 3 trial of droxidopa for nOH in PD (ClinicalTrials.gov Identifier:
      NCT01176240). METHODS: PD patients with documented nOH underwent <= 2 weeks of
      double-blind droxidopa or placebo dosage optimization followed by 8 weeks of
      maintenance treatment (100-600 mg t.i.d.). The primary efficacy measure was
      change in Orthostatic Hypotension Questionnaire (OHQ) composite score from
      baseline to Week 8. Key secondary variables included dizziness/lightheadedness
      score (OHQ item 1) and patient-reported falls. RESULTS: Among 24 droxidopa and 27
      placebo recipients, mean OHQ composite-score change at Week 8 was -2.2 versus 
      2.1 (p = 0.98); in response to this pre-planned futility analysis, the study was
      temporarily stopped and all data from these patients were considered exploratory.
      At Week 1, mean dizziness/lightheadedness score change favored droxidopa by 1.5
      units (p = 0.24), with subsequent numerical differences favoring droxidopa
      throughout the observation period, and at Week 1, mean standing systolic blood
      pressure change favored droxidopa by 12.5 mmHg (p = 0.04). Compared with placebo,
      the droxidopa group exhibited an approximately 50% lower rate of reported falls
      (p = 0.16) and fall-related injuries (post-hoc analysis). CONCLUSIONS: This
      exploratory analysis of a small dataset failed to show benefit of droxidopa, as
      compared with placebo by the primary endpoint. Nonetheless, there were signals of
      potential benefit for nOH, including improvement in dizziness/lightheadedness and
      reduction in falls, meriting evaluation in further trials.

PMID- 24326694
TI  - Evolutionary increases in defense during a biological invasion.
AB  - Invasive plants generally escape from specialist herbivores of their native
      ranges but may experience serious damage from generalists. As a result, invasive
      plants may evolve increased resistance to generalists and tolerance to damage. To
      test these hypotheses, we carried out a common garden experiment comparing 15
      invasive populations with 13 native populations of Chromolaena odorata, including
      putative source populations identified with molecular methods and binary choice
      feeding experiments using three generalist herbivores. Plants from invasive
      populations of C. odorata had both higher resistance to three generalists and
      higher tolerance to simulated herbivory (shoot removal) than plants from native
      populations. The higher resistance of plants from invasive populations was
      associated with higher leaf C content and densities of leaf trichomes and
      glandular scales, and lower leaf N and water contents. Growth costs were detected
      for tolerance but not for resistance, and plants from invasive populations of C.
      odorata showed lower growth costs of tolerance. Our results suggest that invasive
      plants may evolve to increase both resistance to generalists and tolerance to
      damage in introduced ranges, especially when the defense traits have low or no
      fitness costs. Greater defenses in invasive populations may facilitate invasion
      by C. odorata by reducing generalist impacts and increasing compensatory growth
      after damage has occurred. 

PMID- 24326695
TI  - Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated
      Patients With Supratherapeutic International Normalized Ratios?
AB  - The management of upper gastrointestinal bleeding (UGIB) in anticoagulated
      patients with supratherapeutic international normalized ratios (INRs) presents a
      challenge. The purpose of the study was to evaluate the safety of endoscopic
      therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of
      rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated
      patients who underwent endoscopic treatment for UGIB were enrolled in the study.
      Patients were divided into 2 groups based on the occurrence of rebleeding within
      30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and
      rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from
      gastric cancer and bleeding at the duodenum were significantly related to
      rebleeding in a univariate analysis. Multivariate analysis determined that
      presenting symptoms other than melena (hematemesis, hematochezia, or others)
      (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric
      cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant
      factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic
      therapy was not significantly associated with rebleeding in either univariate or
      multivariate analysis. Significant differences in bleeding-related mortality,
      additional intervention to control bleeding, length of hospital stay, and
      transfusion requirements were revealed between the rebleeding and no-rebleeding
      groups. There were no significant differences in therapeutic outcomes between
      patients with INR within the therapeutic range and those with supratherapeutic
      INR. Supratherapeutic INR at the time of endoscopic therapy did not change
      rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy
      for UGIB in anticoagulated patients, irrespective of INR at the time of
      endoscopic therapy. 

PMID- 24326696
TI  - Warfarin and Aspirin Use for Stroke Prevention Among Patients With Atrial
      Fibrillation: The US National Health and Wellness Survey.
AB  - Vitamin K antagonist (VKA) and aspirin (ASA) are recommended for stroke
      prevention in patients with atrial fibrillation (AF). This study examined VKA and
      ASA use and their clinical correlates, including CHADS2 stroke risk scores, among
      adult patients with AF in the general population. Participants included 1290
      (1.72%) adults reporting diagnosis with AF (mean age, 64.9 years; 65% men) from
      the 2009 US National Health and Wellness Survey, an online, self-administered,
      nationwide, stratified random sample survey of 75,000 adults. Antithrombotic use
      patterns, including VKA, ASA, VKA+ASA, and non-VKA/ASA, and their correlates were
      examined using logistic regressions. Respondents with AF were treated with VKA
      (26.6%), ASA (34.5%), VKA+ASA (15.4%), or neither (23.5%). Among those with
      CHADS2 >=1, 19.3% did not report use of VKA or ASA. Among those with CHADS2 >=2,
      35.7% were treated only with ASA. Adjusting for covariates in logistic
      regressions, CHADS2 >=1 was associated with VKA and/or ASA (vs. non-VKA/ASA) use
      (P <= 0.02), but CHADS2 score did not differentiate VKA versus ASA use (P > 0.4).
      Comorbidities were associated with ASA versus VKA use (P <= 0.01). Older age,
      male gender, married status, and obesity were each associated with use of at
      least one of the treatments investigated (all P < 0.05). One-in-five AF patients
      with CHADS2 >=1 were untreated and more than one-third with CHADS2 >=2 treated
      with only ASA for stroke prevention. Our findings suggest that although patient
      characteristics including CHADS2 score were associated with either VKA or ASA
      use, CHADS2 score was unrelated to VKA versus ASA treatment. 

PMID- 24326697
TI  - Albinism in barley androgenesis.
AB  - Androgenesis is highly useful for plant breeding, significantly reducing breeding
      cycle times, as well as in a wide range of biological research. However, for
      widespread use this process must be efficient. Despite several decades of
      research on the phenomenon of androgenesis, many processes involved are obscure
      and there is much to be understood about androgenesis. One of the problems
      inherent in androgenesis, and reducing its efficiency, is albinism. This article
      reviews albinism in barley anthers and microspores in vitro cultures. Of special
      interest is the fate of plastids throughout androgenesis, which is important at
      several levels, including the genes responsible for driving the green-to-albino
      ratios. We also summarize the external factors that reduce the incidence of
      albino plants that are regenerated via androgenesis. 

PMID- 24326699
TI  - Fast and simple epidemiological typing of Pseudomonas aeruginosa using the double
      locus sequence typing (DLST) method.
AB  - Although the molecular typing of Pseudomonas aeruginosa is important to
      understand the local epidemiology of this opportunistic pathogen, it remains
      challenging. Our aim was to develop a simple typing method based on the
      sequencing of two highly variable loci. Single-strand sequencing of three highly
      variable loci (ms172, ms217, and oprD) was performed on a collection of 282
      isolates recovered between 1994 and 2007 (from patients and the environment). As
      expected, the resolution of each locus alone [number of types (NT) = 35-64; index
      of discrimination (ID) = 0.816-0.964] was lower than the combination of two loci
      (NT = 78-97; ID = 0.966-0.971). As each pairwise combination of loci gave similar
      results, we selected the most robust combination with ms172 [reverse; R] and
      ms217 [R] to constitute the double-locus sequence typing (DLST) scheme for P.
      aeruginosa. This combination gave: (i) a complete genotype for 276/282 isolates
      (typability of 98%), (ii) 86 different types, and (iii) an ID of 0.968. Analysis
      of multiple isolates from the same patients or taps showed that DLST genotypes
      are generally stable over a period of several months. The high typability,
      discriminatory power, and ease of use of the proposed DLST scheme makes it a
      method of choice for local epidemiological analyses of P. aeruginosa. Moreover,
      the possibility to give unambiguous definition of types allowed to develop an
      Internet database ( http://www.dlst.org ) accessible by all.

PMID- 24326700
TI  - Pentalenene formation mechanisms redux.
AB  - Quantum chemical calculations are used to assess various means of lowering the
      barrier for the dyotropic rearrangement previously proposed to occur during the
      carbocation rearrangement process promoted by pentalenene synthase. Several means
      of lowering this barrier, including a stepwise pathway for dyotropic
      rearrangement, are uncovered. 

PMID- 24326701
TI  - [The future of scientific libraries].
AB  - "Making predictions is always very difficult, especially about the future". Niels
      Bohr's quote is very appropriate when looking into the future of libraries. If
      the Web is now the richest library in the world, it is also the most friendly and
      therefore the most convenient. The evolution of libraries in the coming years -
      both traditional and online - will probably depend on their ability to meet the
      information needs of users: improved ease of use and better reliability of the
      information. These are objectives that require money and - given the general
      reduction in budgets - it is not obvious that the results will be achieved.
      However, there are many promising experiences at the international level that
      show that the world of libraries is populated by projects and creativity.
      Traditional or digital, libraries will increasingly present themselves more as a
      sharing tool than as a repository of information: it is the sharing that
      translates data into knowledge. In the healthcare field, the integration of
      online libraries with the epidemiological information systems could favor the
      fulfillment of unconscious information needs of health personnel; libraries will
      therefore be a key tool for an integrated answer to the challenge of continuing
      education in medicine. The Internet is no longer a library but an information
      ecosystem where the data are transformed into knowledge by sharing and
      discussion. 

PMID- 24326702
TI  - [Clinical practice guidelines and knowledge management in healthcare].
AB  - Clinical practice guidelines are key tools for the translation of scientific
      evidence into everyday patient care. Therefore guidelines can act as cornerstones
      of evidence based knowledge management in healthcare, if they are trustworthy,
      and its recommendations are not biased by authors' conflict of interests. Good
      medical guidelines should be disseminated by means of virtual
      (digital/electronic) health libraries - together with implementation tools in
      context, such as guideline based algorithms, check lists, patient information,
      a.s.f. The article presents evidence based medical knowledge management using the
      German experiences as an example. It discusses future steps establishing evidence
      based health care by means of combining patient data, evidence from medical
      science and patient care routine, together with feedback systems for healthcare
      providers. 

PMID- 24326703
TI  - [DECIDE: developing and evaluating communication strategies to support informed
      decisions and practice based on evidence].
AB  - Healthcare systems are offered with a wide range of technologies and services,
      but they have to cope with decreasing resources and the uncertainty about what is
      effective and more appropriate. Making decisions about health care interventions
      is complex. Decisions should be informed by the best available evidence, being
      comprehensive to take into account all the relevant aspects (e.g. efficacy,
      safety, equity, costs), and taken within a limited time period. DECIDE is a
      project funded by the European Community that, using the GRADE methodology, aims
      at implementing strategies to enhance dissemination and communication of
      scientific evidence to support on-time evidence-based decision making in clinical
      practice and healthcare policies. Communication strategies are developed in order
      to address different target audiences, trying to meet their information needs.
      One key target are policy makers and managers who are responsible for coverage
      decision making. 

PMID- 24326704
TI  - [Italian physician's needs for medical information. Retrospective analysis of the
      medical information service provided by Novartis Pharma to clinicians].
AB  - The physician's need for medical information updates has been studied extensively
      in recent years but the point of view of the pharmaceutical industry on this need
      has rarely been considered. This paper reports the results of a retrospective
      analysis of the medical information service provided to Italian physicians by an
      important pharmaceutical company, Novartis Pharma, from 2004 to 2012. The results
      confirm clinicians' appreciation of a service that gives them access to tailored
      scientific documentation and the number of requests made to the network of
      medical representatives has been rising steadily, peaking whenever new drugs
      become available to physicians. The analysis confirms what -other international
      studies have ascertained, that most queries are about how to use the drugs and
      what their properties are. The results highlight some differences between
      different medical specialties: for example, proportionally, neurologists seem to
      be the most curious. This, as well as other interesting snippets, is worth
      further exploration. Despite its limits in terms of representativeness, what
      comes out of the study is the existence of an real unmet need for information by
      healthcare institutions and that the support offered by the pharmaceutical
      industry could be invaluable; its role could go well beyond that of a mere
      supplier to National Healthcare Systems, to that of being recognised as an active
      partner the process of ensuring balanced and evidence-based information. At the
      same time, closer appraisal of clinicians' needs could help the pharma industries
      to improve their communication and educational strategies in presenting their
      latest clinical research and their own products. 

PMID- 24326705
TI  - [Knowledge management and healthcare organizations].
AB  - The present scenario is characterized by a high "environmental turbulence".
      Healthcare professionals and organizations must increase their knowledge, skills
      and attitudes for choosing wisely. Healthcare organizations are complex adaptive
      systems which should use integrated governance systems: knowledge management
      should be a strategic goal. These organizations should become learning
      organizations: they should build and renovate their knowledge in a systematic,
      explicit and definite way.

PMID- 24326706
TI  - [The role of the scientific librarian in HTA:what is the status quo and what are
      the prospects].
AB  - The first Italian experiences of HTA are born inside single hospitals and,
      lately, regional health care systems. In Italy, anyway, no agency had health
      technology assessment as an institutional duty until 2007, the year of the
      founding of the Italian Society of Health Technology Assessment (SIHTA). In times
      of "spending review", the HTA, whose purpose is to make decisions about health
      technologies rational and consistent with a context of scarce resources, is
      increasingly emerging as a priority need of the National Health System. The
      objective of this paper is to analyze if and how the librarian is involved in the
      process of health technology assessment, analyzing the results of a survey
      performed at a selection of Italian research organizations. The analysis of the
      results shows that the Italian situation is still very varied, from the point of
      view of HTA, and health technologies are often introduced without any preliminary
      analysis. The librarian is almost never represented within the HTA evaluation
      group and his/her knowledge of HTA should be improved.

PMID- 24326707
TI  - [Swept away and squashed between myth based medicine and eminence based medicine.
      Metaphor of medical meta-cognition. What are we doing wrong with our patient?].
AB  - Myths have played essential social functions throughout human history, and modern
      medical culture makes no exception. Despite ongoing scientific efforts,
      clinicians still encounter biological phenomena that they can hardly explain. In
      this ocean of uncertainty they continue, either consciously or unconsciously, to
      convey a number of myths, which are also used as professional tools. Although in
      recent decades clinical research and randomized trials have emerged as the main
      arbiters of truth in medicine, there are still large areas of uncertainty that
      are consistently filled up with tradition, common sense and experience. In this
      context, mysticism seldom represent a latent source of error, especially when it
      penetrates education and medical literature, so growing to the role of
      indisputable truth, which can hardly be eradicated. The aim of this article is to
      discuss some paradigmatic examples of medical myths, such as the use of beta
      blockers in patients with heart failure, the risk of administering opioids in
      patients with abdominal pain, the suggestion to drink at least eight glasses of
      water per day, the risk of using contrast media in patients with shellfish
      allergy, the indiscriminate prescription of a huge number of laboratory tests to
      achieve an efficient diagnosis, the use of garlic for treat a kaleidoscope of
      human disorders, fructose as a viable replacement for sucrose, the relationship
      between obesity and mortality or between sex and caloric consumption, and the
      cognitive biases. 

PMID- 24326708
TI  - [Parvovirus B19 in adult: report of two cases].
AB  - Parvovirus B19 infection is asymptomatic in the majority of cases, but the are
      several well-known clinical manifestation. In adults transient aplastic crisis,
      chronic anemia, arthropathy, meningitis, encephalitis, myocarditis and acute
      hepatitis have been described. In this paper the Authors report two cases -
      arthropathy and acute hepatitis - of Parvovirus B19 infection in adults. 

PMID- 24326709
TI  - The NICE acute kidney injury guideline: questions still unanswered.

PMID- 24326710
TI  - The value of case reports in medical education.

PMID- 24326713
TI  - Current uses of smartphones and apps in orthopaedic surgery.

PMID- 24326714
TI  - Towards promoting and assessing clinical compassion.

PMID- 24326715
TI  - Foundation doctors' experience and views of mentoring.

PMID- 24326716
TI  - Don't follow your leader: challenging erroneous decisions.

PMID- 24326717
TI  - National Joint Registry data inaccuracy: a threat to proper reporting.
AB  - INTRODUCTION: The authors set out to investigate the accuracy of the information
      their unit was inputting onto the National Joint Registry. This is important both
      in relation to implant surveillance and also to the use of these data to monitor
      the performance of surgeons. METHOD: A single consultant's arthroplasty patients
      were audited over 12 months. Data taken from the National Joint Registry were
      compared to the operation notes and the hospital's computer system. RESULTS: Of
      78 cases inputted, 27 (35%) were incorrect. Sixteen cases (21%) had the incorrect
      'consultant in charge' recorded, eight cases (10%) had the incorrect 'operating
      surgeon' recorded and three cases (4%) had both errors. The most frequent
      inaccuracies resulted from listing by another consultant and incorrectly recorded
      trainee supervision. These errors were highlighted to the unit and a corrected
      process was designed. The intervention was to implement this process by
      presenting to the involved groups and displaying posters to prevent the error
      producing process. The audit was repeated (after 6 months) showing eradication of
      the problem. DISCUSSION: It is the surgeon's duty to ensure data recorded under
      his/her name are accurate and justify any discrepancies when compared to other
      surgeons. Pooling of patients and supervision of trainees are sources of
      potential error.

PMID- 24326718
TI  - Cerebral mass lesions presenting in a cognitive disorders clinic.

PMID- 24326719
TI  - A patient with low pressure idiopathic intracranial hypertension and multiple
      cranial neuropathies.

PMID- 24326720
TI  - Caseous calcification of the mitral valve annulus.

PMID- 24326721
TI  - Parkinsonism hyperpyrexia syndrome caused by abrupt withdrawal of ropinirole.

PMID- 24326722
TI  - Brainstem abscess presenting with lateral gaze palsy in a healthy adolescent
      patient.

PMID- 24326723
TI  - Tuberculosis of the central nervous system.

PMID- 24326724
TI  - The research that time forgot.

PMID- 24326725
TI  - Horace Evans: royal physician.

PMID- 24326726
TI  - Using savings and investments to beat inflation.

PMID- 24326727
TI  - The future of medical education: blending new with old.

PMID- 24326729
TI  - Is lung protective ventilation beneficial for patients without acute respiratory
      distress syndrome?

PMID- 24326731
TI  - Effect of aerobic exercise on quality of life in population with diabetic
      peripheral neuropathy in type 2 diabetes: a single blind, randomized controlled
      trial.
AB  - OBJECTIVE: To evaluate the effect of 8-week moderate intensity aerobic (heart
      rate reserve 40-60%) exercise on neuropathy quality of life in type 2 diabetes.
      METHODS: A single blind, parallel-group, randomized controlled trial was carried
      out in a tertiary setting. People with type 2 diabetes were eligible for the
      study if they had clinical neuropathy which was defined by a minimum score of
      seven on the Michigan diabetic neuropathy score. Following which, the patients
      were randomly assigned to an 8-week program by a computer-generated random number
      tables to intervention or control group. Repeated measure analysis of variance
      was used for data analysis (p < 0.05 was considered significant). RESULTS: There
      were 47 participants in the control group and 40 participants in the study group
      after randomization but 37 from the control group and 29 from the intervention
      group completed the final analysis. The two groups had a significant difference,
      pre-post intervention in scores of pain (F = 7, p = 0.01), sensory symptoms (F =
      4.60, p = 0.04), restricted activities of daily living (F = 4.97, p = 0.03),
      disruptions in social relationships (F = 5.43, p = 0.02), specific impact on
      quality of life (F = 9.28, p < 0.001) overall quality of life (F = 28.72, p <
      0.001), and total score (F = 31.10, p < 0.001). Degrees of freedom for all the
      components were 1, 62. CONCLUSION: Moderate intensity aerobic exercise is
      cornerstone in improving the quality of life of individuals with peripheral
      neuropathy in type 2 diabetes.

PMID- 24326732
TI  - Intra-abdominal candidiasis and probiotics: we know little but it's time to try.

PMID- 24326733
TI  - Satellite monitoring for carbon monoxide and particulate matter during forest
      fire episodes in Northern Thailand.
AB  - This study explored the use of satellite data to monitor carbon monoxide (CO) and
      particulate matter (PM) in Northern Thailand during the dry season when forest
      fires are known to be an important cause of air pollution. Satellite data,
      including Measurement of Pollution in the Troposphere (MOPITT) CO, Moderate
      Resolution Imaging Spectroradiometer aerosol optical depth (MODIS AOD), and MODIS
      fire hotspots, were analyzed with air pollution data measured at nine automatic
      air quality monitoring stations in the study area for February-April months of
      2008-2010. The correlation analysis showed that daily CO and PM with size below
      10 MUm (PM10) were associated with the forest fire hotspot counts, especially in
      the rural areas with the maximum correlation coefficient (R) of 0.59 for CO and
      0.65 for PM10. The correlations between MODIS AOD and PM10, between MOPITT CO and
      CO, and between MODIS AOD and MOPITT CO were also analyzed, confirming the
      association between these variables. Two forest fire episodes were selected, and
      the dispersion of pollution plumes was studied using the MOPITT CO total column
      and MODIS AOD data, together with the surface wind vectors. The results showed
      consistency between the plume dispersion, locations of dense hotspots, ground
      monitoring data, and prevalent winds. The satellite data were shown to be useful
      in monitoring the regional transport of forest fire plumes.

PMID- 24326734
TI  - Effective Targeted Gene Knockdown in Mammalian Cells Using the piggyBac
      Transposase-based Delivery System.
AB  - Nonviral gene delivery systems are rapidly becoming a desirable and applicable
      method to overexpress genes in various types of cells. We have recently developed
      a piggyBac transposase-based, helper-independent and self-inactivating delivery
      system (pmGENIE-3) capable of high-efficiency transfection of mammalian cells
      including human cells. In the following study, we have assessed the potential of
      this delivery system to drive the expression of short hairpin RNAs to knock down
      genes in human cells. Two independent pmGENIE-3 vectors were developed to
      specifically target knockdown of an endogenous gene, telomerase reverse
      transcriptase (TERT), in telomerase-positive human immortalized cell lines. As
      compared with a transposase-deficient vector, pmGENIE-3 showed significantly
      improved short-term transfection efficiency (~4-fold enhancement, 48 hours
      posttransfection) and long-term integration efficiency (~5-fold enhancement)
      following antibiotic selection. We detected a significant reduction of both TERT
      expression and telomerase activity in both HEK293 and MCF-7 breast carcinoma
      cells transfected with two pmGENIE-3 construct targeting distinct regions of
      TERT. Importantly, this knockdown of expression was sufficient to abrogate
      telomerase function since telomeres were significantly shortened (3-4 Kb, P <
      0.001) in both TERT-targeted cell lines following antibiotic selection of stable
      integrants. Together, these data show the capacity of the piggyBac nonviral
      delivery system to stably knockdown gene expression in mammalian cells and
      indicate the potential to develop novel tumor-targeting therapies.Molecular
      Therapy-Nucleic Acids (2013) 2, e137; doi:10.1038/mtna.2013.61; published online
      3 December 2013. 

PMID- 24326735
TI  - The utility of stage-specific mid-to-late Drosophila follicle isolation.
AB  - Drosophila oogenesis or follicle development has been widely used to advance the
      understanding of complex developmental and cell biologic processes. This methods
      paper describes how to isolate mid-to-late stage follicles (Stage 10B-14) and
      utilize them to provide new insights into the molecular and morphologic events
      occurring during tight windows of developmental time. Isolated follicles can be
      used for a variety of experimental techniques, including in vitro development
      assays, live imaging, mRNA expression analysis and western blot analysis of
      proteins. Follicles at Stage 10B (S10B) or later will complete development in
      culture; this allows one to combine genetic or pharmacologic perturbations with
      in vitro development to define the effects of such manipulations on the processes
      occurring during specific periods of development. Additionally, because these
      follicles develop in culture, they are ideally suited for live imaging studies,
      which often reveal new mechanisms that mediate morphological events. Isolated
      follicles can also be used for molecular analyses. For example, changes in gene
      expression that result from genetic perturbations can be defined for specific
      developmental windows. Additionally, protein level, stability, and/or
      posttranslational modification state during a particular stage of follicle
      development can be examined through western blot analyses. Thus, stage-specific
      isolation of Drosophila follicles provides a rich source of information into
      widely conserved processes of development and morphogenesis. 

PMID- 24326736
TI  - Patient outcomes using the European label for dabigatran. A post-hoc analysis
      from the RE-LY database.
AB  - In the RE-LY trial dabigatran 150 mg twice daily (D150) showed significantly
      fewer strokes, and 110 mg (D110) significantly fewer major bleeding events (MBE)
      compared to well-controlled warfarin in patients with atrial fibrillation (AF).
      The European (EU) label currently recommends the use of D150 in AF patients who
      are aged < 80 years without an increased risk for bleeding (e.g. HAS-BLED score
      <3) and not on concomitant verapamil. In other patients, D110 is recommended. In
      this post-hoc analysis of the RE-LY dataset, we simulated how dabigatran
      (n=6,004) would compare to well-controlled warfarin (n=6,022) used according to
      the EU label. "EU label simulated dabigatran treatment" was associated with
      significant reductions in stroke and systemic embolism (hazard ratio [HR] 0.74;
      95% confidence interval [CI] 0.60-0.91), haemorrhagic stroke (HR 0.22; 95%CI 0.11
      0.44), death (HR 0.86; 95%CI 0.75-0.98), and vascular death (HR 0.80; 95%CI 0.68
      0.95) compared to warfarin. Dabigatran was also associated with less major
      bleeding (HR 0.85; 95%CI 0.73-0.98), life-threatening bleeding (HR 0.72; 95%CI
      0.58-0.91), intracranial haemorrhage (HR 0.28; 95%CI 0.17-0.45), and "any bleeds"
      (HR 0.86; 95%CI 0.81-0.92), but not gastrointestinal major bleeding (HR 1.23;
      95%CI 0.96-1.59). The net clinical benefit was significantly better for
      dabigatran compared to warfarin. In conclusion, this post-hoc simulation of
      dabigatran usage based on RE-LY trial dataset indicates that "EU label simulated
      dabigatran treatment" may be associated with superior efficacy and safety
      compared to warfarin, and are in support of the EU label and the 2012 European
      Society of Cardiology AF guideline recommendations. Thus, adherence to European
      label/guideline use results in a clinically relevant benefit for dabigatran over
      warfarin, for both efficacy and safety. 

PMID- 24326737
TI  - A rapid in situ immobilization of D-amino acid oxidase based on immobilized metal
      affinity chromatography.
AB  - A rapid in situ immobilization process was developed based on conventional
      separation technique of immobilized metal affinity chromatography (IMAC) and was
      studied in the case of D-amino acid oxidase (DAAO) with binding-enhancing Heli
      tag (His-Arg-Asn-Tyr-Gly-Gly-Cys-Cys-Gly). A recombinant Escherichia coli strain
      JM105 (Deltaase)/pGEMK-R-DAAO-Heli was successfully constructed to synthesize
      chimeric protein DAAO-Heli. Without additional purification procedure, the tagged
      enzyme DAAO-Heli could be directly immobilized to EP-IDA-Ni(2+) support with
      purity of 90 % and DAAO activity of over 70 U/g support. Experimental results
      showed that the immobilized DAAO-Heli was 73 times more thermally stable than
      free enzyme. Besides, it remained 67 % of initial activity after 100 cycles of
      batch catalysis and its operational stability was improved 36 times than that of
      the previously IMAC-immobilized DAAO-His. Furthermore, the epoxy (EP) support
      could be easily recovered and repeatedly used with simple steps, which could
      reduce the immobilization costs significantly. 

PMID- 24326738
TI  - Small-scale slow glucose feed cultivation of Pichia pastoris without repression
      of AOX1 promoter: towards high throughput cultivations.
AB  - Recombinant protein synthesis in Pichia pastoris is generally controlled by the
      strong methanol inducible AOX1 promoter which is repressed by glucose and
      glycerol. In shake flasks, commonly one or two methanol pulses are added per day
      for induction. Such pulse feeding procedure leads to carbon starvation phases,
      which may enhance proteolytic activities and, therefore, cause product losses.
      Starvation between the methanol pulses could be avoided with a continuous
      enzymatic feed of glucose from a glucose-based polymer. The amount of glucose was
      low enough to prevent AOX1 repression by glucose. Energy and carbon were
      continuously supplied for cell maintenance resulting in significantly increased
      cell densities and product activities, as shown here at the example of a fungal
      lipase expressed in P. pastoris. A threefold improvement in measured product
      activity was obtained by applying enzymatic glucose feed and a further
      improvement was achieved by applying a defined mixture of ammonium compounds. The
      strategy described here simplifies the general procedure in shaken cultures by
      allowing the direct continuation of the cultivation from glucose to the methanol
      based production phase without a medium change. It is easily applicable to
      multiwell plates and thus beneficial for high throughput applications. 

PMID- 24326739
TI  - Graphene oxide can induce in vitro and in vivo mutagenesis.
AB  - Graphene oxide (GO) has attracted enormous interests due to its extraordinary
      properties. Recent studies have confirmed the cytotoxicity of GO, we further
      investigate its mutagenic potential in this study. The results showed that GO
      interfered with DNA replication and induced mutagenesis at molecular level. GO
      treatments at concentrations of 10 and 100 MUg/mL altered gene expression
      patterns at cellular level, and 101 differentially expressed genes mediated DNA
      damage control, cell apoptosis, cell cycle, and metabolism. Intravenous injection
      of GO at 4 mg/kg for 5 consecutive days clearly induced formation of
      micronucleated polychromic erythrocytes in mice, and its mutagenesis potential
      appeared to be comparable to cyclophosphamide, a classic mutagen. In conclusion,
      GO can induce mutagenesis both in vitro and in vivo, thus extra consideration is
      required for its biomedical applications.

PMID- 24326740
TI  - Cost effectiveness of a survivorship care plan for breast cancer survivors.
AB  - PURPOSE: Survivorship care plans (SCPs) are recommended for patients who have
      completed primary treatment and are transitioning to routine follow-up care.
      However, SCPs may be costly, and their effectiveness is unproven. The study
      objective was to assess the cost effectiveness of an SCP for breast cancer
      survivors transitioning to routine follow-up care with their own primary care
      physician (PCP) using data from a recent randomized controlled trial (RCT).
      METHODS: Resource use and utility data for 408 patients with breast cancer
      enrolled in the RCT comparing an SCP with standard care (no SCP) were used. The
      intervention group received a 30-minute educational session with a nurse and
      their SCP, and their PCPs received the SCP plus a full guideline on follow-up.
      Analysis assessed the societal costs and quality-adjusted life years (QALYs) for
      the intervention group and the control group over the 2-year follow-up of the
      RCT. Uncertainty concerning cost effectiveness was assessed through nonparametric
      bootstrapping and deterministic sensitivity analysis. RESULTS: The no-SCP group
      had better outcomes than the SCP group: total costs per patient were lower for
      standard care (Canadian $698 v $765), and total QALYs were almost equivalent
      (1.42 for standard care v 1.41 for the SCP). The probability that the SCP was
      cost effective was 0.26 at a threshold value of a QALY of $50,000. A variety of
      sensitivity analyses did not change the conclusions of the analysis. CONCLUSION:
      This SCP would be costly to introduce and would not be a cost effective use of
      scarce health care resources.

PMID- 24326742
TI  - XIAP deficiency is a mendelian cause of late-onset IBD.

PMID- 24326741
TI  - Multinational, double-blind, randomised, placebo-controlled, prospective study of
      esomeprazole in the prevention of recurrent peptic ulcer in low-dose
      acetylsalicylic acid users: the LAVENDER study.
AB  - OBJECTIVES: To evaluate if esomeprazole prevents recurrent peptic ulcer in adult
      patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid
      (ASA, aspirin) for cardiovascular protection in East Asia. METHODS: In this
      prospective, randomised, double-blind, placebo-controlled trial conducted in
      Japan, Korea and Taiwan, eligible patients receiving low-dose ASA for
      cardiovascular protection (81-324 mg/day) were randomised to esomeprazole 20
      mg/day or placebo for <=72 weeks. All patients received concomitant mucosal
      protection (gefarnate 100 mg/day). The primary endpoint was time to ulcer
      recurrence (Kaplan-Meier analysis). Efficacy findings are presented up to week
      48, as per a planned interim analysis within the study protocol. RESULTS: A total
      of 364 patients (79.9% men; mean age, 67.1 years) comprised the full analysis set
      (esomeprazole, n=182; placebo, n=182). There was a statistically significant
      difference in the time to ulcer recurrence between esomeprazole and placebo (HR
      0.09; 96.65% CI 0.02 to 0.41; p<0.001). The estimated ulcer-free rate at week 12
      was 99.3% (esomeprazole) and 89.0% (placebo). The high estimated ulcer-free rate
      for esomeprazole was maintained through to week 48 (98.3% vs. 81.2% of placebo
      treated patients). No factors, other than female gender, reduced time to ulcer
      recurrence in addition to the effect of esomeprazole (p<0.001). Treatment with
      esomeprazole was generally well tolerated. CONCLUSIONS: Daily esomeprazole 20 mg
      is efficacious and well tolerated in reducing the recurrence of peptic ulcer in
      East-Asian patients with a history of ulcers who are taking low-dose ASA for
      cardiovascular protection. CLINICALTRIALGOV IDENTIFIER: NCT01069939.

PMID- 24326743
TI  - Effect of Nd:YAG laser parameters on the penetration depth of a representative Ni
      Cr dental casting alloy.
AB  - The effects of voltage and laser beam (spot) diameter on the penetration depth
      during laser beam welding in a representative nickel-chromium (Ni-Cr) dental
      alloy were the subject of this study. The cast alloy specimens were butted
      against each other and laser welded at their interface using various voltages
      (160-390 V) and spot diameters (0.2-1.8 mm) and a constant pulse duration of 10
      ms. After welding, the laser beam penetration depths in the alloy were measured.
      The results were plotted and were statistically analyzed with a two-way ANOVA,
      employing voltage and spot diameter as the discriminating variables and using
      Holm-Sidak post hoc method (a = 0.05). The maximum penetration depth was 4.7 mm.
      The penetration depth increased as the spot diameter decreased at a fixed voltage
      and increased as the voltage increased at a fixed spot diameter. Varying the
      parameters of voltage and laser spot diameter significantly affected the depth of
      penetration of the dental cast Ni-Cr alloy. The penetration depth of laser-welded
      Ni-Cr dental alloys can be accurately adjusted based on the aforementioned
      results, leading to successfully joined/repaired dental restorations, saving
      manufacturing time, reducing final cost, and enhancing the longevity of dental
      prostheses. 

PMID- 24326744
TI  - 1064 Nd:YAG laser for the treatment of chronic paronychia: a pilot study.
AB  - Paronychia, which can be acute or chronic, is characterized by erythema, edema,
      and tenderness at the proximal and occasionally lateral nail folds. Causes of
      chronic paronychia include excessive moisture, contact irritants, trauma, and
      candida infection. Chronic paronychia is usually multifactorial and difficult to
      treat. The aim of the present work was to assess the role of neodymium-doped
      yttrium aluminium garnet (Nd:YAG) laser as a new modality for the treatment of
      chronic paronychia. In this interventional pilot study, eight female patients
      suffering from long-standing paronychia received 2-5 Nd:YAG laser sessions (4
      weeks apart). Fluences ranged between 70 to 80 J/cm(2), using a 2.5-mm spot size
      handpiece, and pulse duration was set at 0.7 ms. Patients were digitally
      photographed and clinically evaluated before starting the treatment and at each
      session. Seven of our patients showed various degree of improvement regarding
      erythema and swelling of their proximal nail folds. Nail plate abnormalities also
      improved in six patients. These preliminary results document the efficacy and
      feasibility of Nd:YAG laser as one of the treatments that could ameliorate
      chronic paronychia. 

PMID- 24326745
TI  - The effectiveness of low-level laser therapy in accelerating orthodontic tooth
      movement: a meta-analysis.
AB  - Low-level laser therapy is claimed to accelerate bone remodeling. The aim of this
      meta-analysis was to critically appraise current evidence and to determine the
      effectiveness of low-level laser therapy in accelerating orthodontic tooth
      movement. PubMed, Web of Knowledge, Embase, CENTRAL, ProQuest Dissertations
      &Theses, and SIGLE were electronically searched from Jan 1990 to Jun 2013.
      Article screening, data extraction, assessment of risk of bias and evaluation of
      evidence quality through GRADE were conducted independently and in duplicate by
      two reviewer authors. Outcome of interest in this meta-analysis was accumulative
      moved distance (AMD). Meta-analyses were performed in Comprehensive Meta-Analysis
      Version 2.2.064 (Biostat, Englewood, NJ, USA). Finally, five studies were
      included in this meta-analysis. The meta-analysis revealed that the pooled
      difference in mean (DM) was 0.33 [95 % CI: (0.03-0.64)], 0.76 [95 % CI: (-0.14,
      1.65)] and 0.43 [95 % CI: (-0.05, 0.91)] for AMD within 1 month, AMD within 2
      months and AMD within 3 months, respectively. However, significant
      heterogeneities and instability of the pooled results were detected. Moreover,
      publication bias was found for AMD within 3 months. The subgroup analysis on the
      wavelength of 780 nm revealed that the pooled DM of AMD were 0.54 (95 % CI = 0.18
      0.91), 1.11 (95 % CI = 0.91-1.31) and 1.25 (95 % CI = 0.68-1.82) for 1, 2, and 3
      months, respectively. For the output power of 20 mW, the subgroup analysis showed
      that the pooled DM of AMD was 0.45 (95 % CI = 0.26-0.64), 1.11 (95 % CI = 0.91
      1.31), and 1.25 (95 % CI = 0.68-1.82) for 1, 2, and 3 months, respectively. Weak
      evidence suggests that low-level laser irradiations at the wavelength of 780 nm,
      at the fluence of 5 J/cm(2) and/or the output power of 20 mW could accelerate
      orthodontic tooth movement within 2 months and 3 months. However, we cannot
      determine its effectiveness within 1 month due to potential measurement errors.

PMID- 24326746
TI  - Factors associated with adoption of robotic surgical technology in US hospitals
      and relationship to radical prostatectomy procedure volume.

PMID- 24326747
TI  - Patient value is superior with early surgery for acute cholecystitis.

PMID- 24326748
TI  - Fetal Alcohol Spectrum Disorder (FASD): neurobehavioral profile, indications for
      diagnosis and treatment.
AB  - It is now known that exposure to alcohol in utero produces a wide spectrum of
      morphological and behavioural outcomes in the offspring, commonly referred as
      fetal alcohol spectrum disorders (FASD). A large body of literature documents
      cognitive deficits and behavioural-emotional difficulties in children with FASD.
      Researchers have found that individuals with FASD often experience a range of
      adverse life outcomes, called secondary disabilities, which include disrupted
      school experience, troubles with the law, confinement, inappropriate sexual
      behaviours on repeated occasions, and alcohol/drug related problems.
      Additionally, despite considerable data published on cognitive and behavioural
      disabilities in children with FASD, relatively little information is available on
      behavioural or pharmacological interventions for alcohol affected children. This
      paper will provide a comprehensive review of the neuropsychological and
      behavioural effects of prenatal alcohol exposure, including a discussion of the
      emerging neurobehavioral profile. Finally, we will summarize published
      intervention studies of FASD focusing on their strengths and weaknesses.

PMID- 24326749
TI  - [Symptoms related to addiction: elements for the differential diagnosis with
      personality disorders].
AB  - Some manifestations, observed in situations of addiction, are often interpreted
      as symptoms of a personality disorder. On the contrary, they may not be referable
      to personality structural aspects, but they hold rather a functional aspect,
      linked to the implications of the relationship between the individual and the
      object of addiction. In particular, the personal meaning given to addiction holds
      an important role as regards the intensity of this relationship. This recalls the
      necessity of a thorough examination for differential diagnosis. The awareness of
      intervening in behaviour modalities, due to the process of addiction and not to
      preexistent personality features, modifies the perspective of action. As a
      result, generic modalities of treatment, leading to confused therapeutic routes,
      would be overcome, presuming that acting on other aspects interferes in addiction
      phenomena. In that way, it would be possible to pick out specific routes to act
      from the therapeutic point of view on the focus of addiction. The recovery of the
      meaning the patient gives to it and a following elaboration can bring to the
      awareness of different emotional and behavioural options to face moments that can
      reestablish the individual emotional process at the basis of addiction. From an
      organizational point of view, it would be possible to reserve the articulated and
      complex interventions for cases of comorbidity to those who really require. 

PMID- 24326750
TI  - [The endocannabinoid system and its possible role in neurobiology of psychiatric
      disorders].
AB  - In the last years, numerous researches led to identify endocannabinoid system, a
      sophisticated short-range signaling system which is located both in Central
      Nervous System (CNS) and in whole organism. Because of its flexibility of
      expression, it plays a modulatory role in controlling the answers to stimuli
      which disturb homeostasis. On one hand it lets them occur whilst on the other it
      limits them in order to protect organism from consequences due to excessive
      reaction. In the CNS, endocannabinoid system is able to control the release of
      several neurotransmitters thanks to its retrograde signaling, modulating synaptic
      activity. Analysing this property during preclinical studies, it came out that
      the endocannabinoid system is involved in numerous physiologic processes, such as
      neuroendocrine axes, food consumption, brain reward and satisfaction mechanisms,
      memories storing and extinction, emotions and neurodevelopment regulation. Such
      discoveries have led researchers to suppose and investigate an alteration of this
      system in the physiopathology of some psychiatric disorders such as anxiety
      disorder, depression, eating disorders, addiction and schizophrenia. Results of
      such studies on animal models show a possible involvement of this system and were
      quickly followed by clinical studies which seem to confirm it. These findings
      might open new scenarios for understanding the pathogenesis of several
      psychiatric disorders and, at same time, they show new prospects for their
      treatment. 

PMID- 24326751
TI  - [Recovery style, symptoms and psychosocial functioning in psychotic patients: a
      preliminary study].
AB  - BACKGROUND: Both integration and sealing over have been identified as global,
      clinically distinct recovery styles from the psychotic illness. The aim of this
      study was to investigate the correlation between recovery style, symptoms and
      global functioning in psychotic patients. METHODS: 106 psychiatric patients in
      different phases of recovery were studied (no patient at the first episode in our
      sample). The Integration/Sealing Over Scale, the Recovery Style Questionnaire,
      the Positive and Negative Syndrome Scale and the Life Skills Profile were
      completed for all patients; moreover, socio-demographic and clinical data were
      collected. RESULTS: A relationship was found between the integrative recovery
      style and age >45 years (p<0.05), integration and affective disorders (p<0.05),
      delusions and sealing over (p<0.05). CONCLUSIONS: Although the limited study
      sample, our findings suggest some predictors of integration which should be taken
      into consideration to "drive" patients toward an integrative recovery style after
      an acute psychotic episode.

PMID- 24326752
TI  - [Psychiatric features before and after intervention: a study of patients affected
      by severe obesity undergoing adjustable gastric banding].
AB  - AIM: This study identifies psychological features and the evolution of
      psychiatric symptoms in a group of patients affected by obesity, who underwent
      adjustable gastric banding. MATERIALS AND METHODS: In this group, other than
      clinical visit, test SCL-90 is made in preoperative time. In postoperative SCL
      90, TAS and BES were carried out. Patients evaluated before and after bariatric
      surgery were 220 and 115, respectively. SCL-90 test made before bariatric surgery
      showed high values (>0.7) for cluster related to somatization, interpersonal
      sensitivity, paranoid ideation, depression and obsessive compulsive disorder.
      DISCUSSION: Depression symptoms were more important in patients undergoing
      endogastric balloon placement (mean value of 0.9). Anxious symptoms showed a mean
      value of 0.73 in patients undergoing endogastric balloon placement as compared to
      a mean value of 0.52 in patients undergoing gastric banding. CONCLUSIONS: Our
      findings show that in patients undergoing bariatric surgery, depressive symptoms
      are more common preoperatively and normalize at follow-up. This confirms that a
      possible cause of depression is obesity. The present study also shows that
      anxious symptoms are lower in obese patients.

PMID- 24326753
TI  - [Female sexual functioning: the role of psychopathology].
AB  - BACKGROUND: In the study of the relationship between sexuality and
      psychopathology, female sexual functioning appears to be relatively poorly
      explored. In addition, most studies have been conducted on clinical samples, so
      that the question of whether non-clinically relevant psychopathological symptoms
      may have a negative impact on women's sexual response still remains unanswered.
      The aim of this study was to analyze the influence of psychopathology on specific
      phases of sexual functioning (desire, arousal, lubrication, orgasm, satisfaction)
      and pain in a sample of young women without psychiatric case history. METHODS:
      Two questionnaires were administered to a sample of female students in Psychology
      of the University of Florence (n=75): the Symptom Checklist (SCL-90) to evaluate
      psychic distress and the Female Sexual Function Index (FSFI) for data collection
      on sexual functioning. RESULTS: 44 questionnaires were valid. The dimensions of
      SCL-90 explain a relatively high percentage of variance of the global severity
      index of sexuality (R2=0.49); significant predictors were: somatization (Beta=
      0.75), depression (Beta=-0.89), anxiety (Beta=-0.79), and hostility (Beta=-0.48).
      The same variables were significant predictors, though at a lesser extent, for
      all the single dimensions of sexuality, with the exception of pain, on which only
      hostility had a significant correlation (Beta=-0.55). CONCLUSIONS: Although the
      small size and the peculiar characteristics of the sample do not allow to
      extrapolate the results, the findings of this study show that psychopathological
      dimensions can affect female sexual functioning at subclinical level in the
      absence of the confounding effect of drug therapy.

PMID- 24326754
TI  - pH-Impedance Findings and proton pump inhibitors-responsiveness in patients with
      typical gastroesophageal reflux disease symptoms in a large single-center Italian
      series.
AB  - INTRODUCTION: A multicenter study with a limited sample size found that absence
      of esophagitis, presence of functional digestive disorders, and overweight were
      associated with proton pump inhibitors (PPI) failure. AIM: To assess clinical and
      reflux patterns associated with PPI-responsiveness. MATERIALS AND METHODS:
      Patients with typical gastroesophageal reflux disease (GORD) symptoms had 24
      hours pH-impedance monitoring off therapy. Responders had <2 days of symptoms per
      week while on standard-dose/double-dose PPI. Clinical and reflux parameters were
      considered for analysis. RESULTS: A total of 514 patients were included (267
      women), 185 patients were considered PPI responders, and 329 were considered
      nonresponders. In the whole population, the only significant factor in the
      prediction of responsiveness to PPI at the multivariate analysis was the presence
      of esophagitis (P=0.028). The factors identified as significant in patients with
      a pathologic acid exposure (142 patients) in the prediction of responsiveness to
      PPI were overweight (body mass index >25 kg/m(2)) and the presence of esophagitis
      (P=0.019 and 0.043, respectively). CONCLUSIONS: We confirm that no reflux pattern
      demonstrated by 24 hours pH-impedance monitoring is associated to PPI response in
      GORD patients. Presence of esophagitis in the whole population and overweight in
      patients with pathologic GORD, but not dyspepsia, are strongly associated with
      PPI-responsiveness.

PMID- 24326755
TI  - Edwardsiella tarda superinfection in relapse of ulcerative colitis.

PMID- 24326758
TI  - Tumour lysis syndrome.
AB  - Tumour lysis syndrome is a group of metabolic abnormalities that result from the
      rapid release of intracellular metabolites such as nucleic acids, proteins,
      phosphorus and potassium from lysed malignant cells. 

PMID- 24326756
TI  - What are the characteristics of breast cancers misclassified as benign by
      quantitative ultrasound shear wave elastography?
AB  - OBJECTIVES: Shear wave elastography (SWE) is a promising adjunct to greyscale
      ultrasound in differentiating benign from malignant breast masses. The purpose of
      this study was to characterise breast cancers which are not stiff on quantitative
      SWE, to elucidate potential sources of error in clinical application of SWE to
      evaluation of breast masses. METHODS: Three hundred and two consecutive patients
      examined by SWE who underwent immediate surgery for breast cancer were included.
      Characteristics of 280 lesions with suspicious SWE values (mean stiffness >50
      kPa) were compared with 22 lesions with benign SWE values (<50 kPa). Statistical
      significance of the differences was assessed using non-parametric goodness-of-fit
      tests. RESULTS: Pure ductal carcinoma in situ (DCIS) masses were more often soft
      on SWE than masses representing invasive breast cancer. Invasive cancers that
      were soft were more frequently: histological grade 1, tubular subtype, <=10 mm
      invasive size and detected at screening mammography. No significant differences
      were found with respect to the presence of invasive lobular cancer, vascular
      invasion, hormone and HER-2 receptor status. Lymph node positivity was less
      common in soft cancers. CONCLUSION: Malignant breast masses classified as benign
      by quantitative SWE tend to have better prognostic features than those correctly
      classified as malignant. KEY POINTS: * Over 90 % of cancers assessable with
      ultrasound have a mean stiffness >50 kPa. * 'Soft' invasive cancers are
      frequently small (<=10 mm), low grade and screen-detected. * Pure DCIS masses are
      more often soft than invasive cancers (>40 %). * Large symptomatic masses are
      better evaluated with SWE than small clinically occult lesions. * When assessing
      small lesions, 'softness' should not raise the threshold for biopsy.

PMID- 24326759
TI  - Interpretation of iron studies.
AB  - Iron plays a vital role in the human body in oxygen transport, mitochondrial
      oxidative energy production, inactivation of drugs and toxins, and DNA synthesis
      (Munoz et al, 2011). 

PMID- 24326757
TI  - Wall morphology, blood flow and wall shear stress: MR findings in patients with
      peripheral artery disease.
AB  - OBJECTIVES: To investigate the influence of atherosclerotic plaques on femoral
      haemodynamics assessed by two-dimensional (2D) phase-contrast (PC) magnetic
      resonance imaging (MRI) with three-directional velocity encoding. METHODS: During
      1 year, patients with peripheral artery disease and an ankle brachial index <1.00
      were enrolled. After institutional review board approval and written informed
      consent, 44 patients (age, 70 +/- 12 years) underwent common femoral artery MRI.
      Patients with contra-indications for MRI were excluded. Sequences included 2D
      time-of-flight, proton-density, T1-weighted and T2-weighted MRI.
      Electrocardiogram (ECG)-gated 2D PC-MRI with 3D velocity encoding was acquired. A
      radiologist classified images in five categories. Blood flow, velocity and wall
      shear stress (WSS) along the vessel circumference were quantified from the PC-MRI
      data. RESULTS: The acquired images were of good quality for interpretation. There
      were no image quality problems related to poor ECG-gating or slice positioning.
      Velocities, oscillatory shear stress and total flow were similar between patients
      with normal arteries and wall thickening/plaque. Patients with plaques
      demonstrated regionally increased peak systolic WSS and enhanced WSS
      eccentricity. CONCLUSIONS: Combined multi-contrast morphological imaging of the
      peripheral arterial wall with PC-MRI with three-directional velocity encoding is
      a feasible technique. Further study is needed to determine whether flow is an
      appropriate marker for altered endothelial cell function, vascular remodelling
      and plaque progression. KEY POINTS: * Femoral plaques are associated with altered
      dynamics of peripheral blood flow. * Multi-contrast MRI can investigate the
      presence and type of atherosclerotic plaques. * Three-dimensional velocity
      encoding phase-contrast MRI can investigate flow and wall shear stress. *
      Atherosclerotic peripheral arteries demonstrate increased systolic velocities and
      wall shear stress.

PMID- 24326760
TI  - An introduction to pain pathways and mechanisms.
AB  - Pain is a vital function of the nervous system in providing the body with a
      warning of potential or actual injury. It is both a sensory and emotional
      experience, affected by psychological factors such as past experiences, beliefs
      about pain, fear or anxiety. 

PMID- 24326761
TI  - Obstetric hysterectomy: a life saving emergency.
AB  - OBJECTIVE: To study the cases of obstetric hysterectomy performed over a period
      of 1 year (January 2008 to December 2008) in tertiary care center to estimate the
      incidence, indications, and maternal outcome following the procedure. MATERIALS
      AND METHODS: A retrospective analysis of 20 cases of emergency obstetric
      hysterectomies performed during the study period. RESULTS: During the study
      period, there were 11,356 deliveries and 20 emergency hysterectomies were done,
      giving an incidence of 0.17%. 75% cases were unbooked. Ruptured uterus was the
      most common indication for the procedure, followed by atonic Post-partum
      haemorrhage (PPH). Six out of 10 cases of rupture uterus had a previous cesarean
      delivery. Maternal mortality was 15% due to late referral. CONCLUSION: Emergency
      obstetric hysterectomy though a rare operation, still remains a life-saving
      procedure with which every obstetrician must be conversant. Regular antenatal
      care, identification of high-risk cases, and prompt referral can reduce the
      incidence of this operation.

PMID- 24326762
TI  - The economic burden of hemodialysis in Jordan.
AB  - BACKGROUND: Hemodialysis treatment is a costly procedure that requires specific
      resources. It has a considerable burden on patients, caregivers, and healthcare
      system. The aim of this study was to estimate the economic burden borne by the
      Ministry of Health (MOH) in Jordan, with a focus on direct medical, direct non
      medical, and indirect cost. MATERIALS AND METHODS: The study was conducted at MOH
      hospitals in Jordan, from August to November 2010. A total of 138 patients and 49
      caregivers were involved in the study. An economic evaluation study was used to
      analyze the burden of hemodialysis treatment at MOH, Jordan. Direct medical costs
      were estimated through micro and macro costing from the provider's perspective.
      Patients' and caregivers' costs were included to calculate direct non-medical
      costs. Human capital approach was employed to evaluate the productivity loss for
      indirect cost and premature death and potential year life loss was used to
      estimate the premature death cost. RESULTS: The total burden of hemodialysis at
      MOH, Jordan was USD17.70 million per year. Cost per session was $72 and the
      annual cost per patient was $9976. Direct medical cost was $7.20 million (41%)
      and direct non-medical cost was $2.02 million (11%). On the other hand, indirect
      cost (productivity loss) was $8.48 million (48%). All 722 patients on
      hemodialysis at MOH hospitals consumed 2.7% of MOH budget. CONCLUSIONS: Costs of
      treating and managing patients on hemodialysis at MOH hospitals in Jordan are
      substantial. Therefore, efforts should be taken to slow down the progress of
      renal failure to save resources and a comparative study with other modalities,
      such as continuous ambulatory peritoneal dialysis and kidney transplantation,
      should be considered.

PMID- 24326763
TI  - Study of parents of beta-thalassemia major children to determine cutoff values of
      hematological parameters for diagnosis of beta-thalassemia trait and assessment
      of anemia in them.
AB  - BACKGROUND: Because of the overlapping MCV, MCH and HbA 2 values in BTT and non
      BTT subjects our laboratory determined own cutoffs. AIMS: To establish cutoff
      values by investigating the parents of thalassemia major children and to assess
      the degree of anemia in BTT subjects. MATERIALS AND METHODS: Study includes 179
      parents of thalassemia major children (BTT cases) and 287 non-BTT controls.
      Samples were analyzed on an electronic hematology analyzer. The samples having
      MCV <= 76 fl and MCH <= 27 pg were quantified for HbA 2 by cellulose acetate
      electrophoresis and grey zone samples were confirmed on HPLC. Statistical
      Analysis Mean +/- SD, sensitivity, specificity, PPV, NPV and accuracy were
      calculated. The histograms were plotted for MCV, MCH and HbA 2 . RESULTS: Cases
      having MCV <= 76 fl and MCH <= 27 pg if considered as suspected cases of BTT then
      we could have missed five known BTT samples. Sensitivity increased to 100% in all
      three diagnostic parameters when the cutoff values were raised and specificity
      for MCV and MCH was decreased. But specificity was 100% with raised cutoff for
      HbA 2 . Hb and HCT mean values were significantly reduced in BTT cases compared
      to controls (P < 0.001). In 100% females and 84.9% males having BTT, mild to
      moderate anemia was observed. CONCLUSION: In our setup, the cutoff values are MCV
      (<=78.0 fl), MCH (<=28 pg) and HbA 2 (>3.8%) for BTT diagnosis and there is a
      mild to moderate anemia in BTT cases.

PMID- 24326764
TI  - Activities of serum Ada, GGT and alp in carcinoma breast-a case control study for
      diagnostic and prognostic significance.
AB  - AIM: To assess the clinical utility of Serum adenosine deaminase, gamma glutamyl
      transferase and alkaline phosphatase in carcinoma breast patients for diagnostic
      and prognostic purpose. MATERIALS AND METHODS: Thirty clinically and
      histopathologically confirmed female patients of the age group of 30-65 years
      served as cases and 30 normal healthy females in the same age group served as
      controls. The parameters were estimated by standard biochemical methods. RESULTS:
      The activities of serum ADA, GGT and ALP were significantly increased in
      carcinoma breast patients when compared to controls. When all the 4 stages of
      carcinoma breast were compared with controls ADA and GGT were increased
      significantly. Whereas ALP showed a significant increase only in stage II, III
      and IV. Interstage comparison yielded a steady and progressive increase in the
      activities of these enzymes from stage I-IV. CONCLUSION: The study concludes that
      enzyme markers like serum ADA and GGT could be sensitive, specific and cost
      effective biomarkers for diagnosing carcinoma breast and for monitoring its
      progression. Serum ALP level can be used as important biomarker for detecting
      metastasis and for differentiation of carcinoma breast with and without
      metastasis.

PMID- 24326765
TI  - Prevalence of diabetes and hypertension among geriatric population in a rural
      community of Tamilnadu.
AB  - INTRODUCTION: Elderly population contributed to 7% of total population of India
      in 2001 and it will rise to 9% by 2016. In 2010,100 million people were aged
      above 60 years and by 2020 it will be 177 million. Ageing process is as such
      complex and multi-factorial. Chronic morbidities like diabetes and hypertension
      are becoming common health problems among the geriatric population. AIM: To
      assess the prevalence of diabetes and hypertension among geriatric population in
      a rural community of Tamilnadu. MATERIALS AND METHODS: A cross-sectional study
      was conducted on 400 geriatric population at Attayampatti village, rural
      community in Salem district by using a pre-tested, semi-structured questionnaire.
      House to house visit was done on simple random basis. Their height and weight was
      measured and body mass index was calculated. The diabetic status was confirmed by
      using random blood sugar estimation and hypertension was assessed by using a
      standard sphygmomanometer apparatus. RESULTS: The overall prevalence of diabetes
      among study population was 36% and the prevalence of hypertension was 59%. Among
      diabetes, the prevalence in males was 22% and in females it was 15%. Among
      hypertensives, the prevalence in males was 33.3% and in females it was 26.2%.
      Their mean BP was 140/100 and the mean random blood sugar was 180 mgs/dl. Factors
      like age, BMI and smoking showed statistical significant association towards
      diabetes and hypertension. CONCLUSION: Early identification of chronic geriatric
      morbidities like diabetes and hypertension should be ensured through periodic
      screening and regular health checkups.

PMID- 24326766
TI  - Bedside utility of clinical scoring systems in classifying stroke.
AB  - BACKGROUND: The study aimed to validate and compare the Siriraj score, Guy's
      hospital score, Greek score, and Besson score in a group of stroke patients.
      MATERIALS AND METHODS: We assessed the stroke scores and compared them to
      computed tomography (CT) scan of brain. RESULTS: Two hundred stroke patients (129
      ischemic stroke) were included. For ischemic stroke, sensitivity and specificity
      were 71% and 92% (Siriraj score), 73% and 98% (Greek score), 59% and 87% (Guy's
      hospital score), and 65% and 98% (Besson score), respectively. For intracranial
      hemorrhage, sensitivity and specificity were 84% and 89% (Siriraj score), 80% and
      99% (Greek score), and 63% and 95% (Guy's hospital score), respectively. Using
      receptor operating characteristic curve, the greatest area under the curve was
      obtained for Greek score (0.973). For bedside accurate and safe diagnosis of
      ischemic stroke, the best cut off was for Greek score (1.5) which identified 47%
      of ischemic stroke patients. CONCLUSIONS: The Greek score appears as the single
      best score. Using the newly developed discriminant cut off value; a substantial
      number of patients may be started with anti-platelet therapy while awaiting CT
      scan of brain.

PMID- 24326767
TI  - Bernard Soulier Syndrome associated with acute myeloid leukemia.
AB  - Bernard Soulier Syndrome is a very rare congenital bleeding disorder
      characterized by deficiency in glycoprotein Ib (Gp Ib) which is vital for clot
      formation. We present a case of 21-year-old girl with onset of menorrhagia since
      4 months. She was investigated and diagnosed to be a case of AML-M4 with
      associated Gp Ib deficiency. 

PMID- 24326768
TI  - A graphene dispersed CdS-MoS2 nanocrystal ensemble for cooperative photocatalytic
      hydrogen production from water.
AB  - We report a simple but highly cooperative ensemble with CdS and MoS2 nanocrystals
      dispersed on graphene sheets: it is demonstrated that CdS nanocrystals can
      capture light energy and facilitate excited electron transfer to MoS2 for
      catalytic hydrogen production via the 2-D graphene which plays a key role as an
      efficient electron mediator. 

PMID- 24326769
TI  - The association between polymorphism of P53 Codon72 Arg/Pro and hepatocellular
      carcinoma susceptibility: evidence from a meta-analysis of 15 studies with 3,704
      cases.
AB  - Emerging evidence has shown that p53gene participates in human carcinogenesis as
      tumor suppressors. Polymorphism of p53 gene codon72 arginine (Arg)/proline (Pro)
      (rs1042522) may influence the function of p53 protein and then affect the
      processing of carcinogenesis. It has been suggested that p53 codon72 Arg/Pro
      polymorphism is associated with susceptibility to hepatocellular carcinoma (HCC).
      However, published results are inconsistent and inconclusive. To examine the
      validity of the association between the polymorphism and HCC risk, we performed
      this meta-analysis. We have conducted a search of case-control studies on the
      associations of p53 codon72 polymorphism with susceptibility to HCC in PubMed,
      ScienceDirect, BioMed central, Springer, EBSCO, Wanfang databases, and Chinese
      National Knowledge Infrastructure databases. A total of 15 studies were
      identified with 3,704 cases and 4,559 controls for codon72 Arg/Pro polymorphism.
      The result did support a significant genetic association between Pro allele and
      susceptibility to HCC in all the genetic models. Similarly, subgroup analysis
      showed significant associations between the Arg/Pro polymorphism and
      susceptibility to HCC when stratifying by race, gender, source of controls, and
      hepatitis virus infection status. This meta-analysis suggests that p53 codon72
      Arg/Pro polymorphism may be associated with the risk of HCC, especially in
      subgroup analysis of Asian and Caucasian population, hospital-based population,
      the female, and the individuals infected with hepatitis virus. However, well
      designed studies based on different ethnic groups with larger sample size and
      more detailed data are needed to confirm these conclusions. 

PMID- 24326770
TI  - Clinicopathological and prognostic significance of chemokine receptor CXCR4
      overexpression in patients with esophageal cancer: a meta-analysis.
AB  - The prognostic significance of CXC chemokine receptor type 4 (CXCR4) for survival
      of patients with esophageal cancer remains controversial. To investigate its
      expression impact on clinicopathological features and survival outcome, a meta
      analysis was performed. A comprehensive search in the PubMed, Embase, and Web of
      Science (up to October 8, 2013) was performed for relevant studies using multiple
      search strategies. Correlation between CXCR4 expression and clinicopathological
      features and overall survival (OS) was analyzed. A total of 1,055 patients with
      esophageal cancer from seven studies were included. The pooled odds ratios (ORs)
      which indicated CXCR4 expression was associated with tumor depth (OR = 0.35,
      confidence interval (CI) = 0.27-0.47, P < 0.00001), status of lymph node (OR =
      0.36, CI = 0.21-0.61, P < 0.0002), TNM (tumor, node, metastasis) stage (OR =
      0.38, CI = 0.25-0.56, P < 0.00001), and histological type (OR = 1.81, CI = 1.07
      3.05, P = 0.03). Poor overall survival of esophageal cancer was found to be
      significantly related to CXCR4 overexpression (hazard ratio (HR) 1.49, 95% CI =
      1.24-1.80, P < 0.0001), whereas combined ORs exhibited that CXCR4 expression has
      no correlation with gender or tumor differentiation. Based on the published
      studies, CXCR4 overexpression in patients with esophageal cancer indicated worse
      survival outcome and was associated with common clinicopathological poor
      prognostic factors.

PMID- 24326771
TI  - Leptospirosis seroprevalence and risk factors for sheep in Maranhao state,
      Brazil.
AB  - This study was conducted to determine leptospirosis seroprevalence in sheep and
      their spatial distribution as well as identify risk factors associated with
      seropositivity in sheep from 37 herds and 11 municipalities in the Presidente
      Dutra microregion, Maranhao state, Brazil. We analyzed 379 blood serum samples
      using a Microscopic Agglutination Test (MAT). The individual seroprevalence was
      32%. Of the 37 herds studied, 30 (81%, 95% CI 69-94%) had at least one
      seropositive animal. In seven municipalities, we observed infection in 100% of
      the herds. The serovars recorded were Grippotyphosa (67%), Wollfi with Hardjo
      (9%), Bratislava (9%), Hardjo (5%), Icterohaemorrhagiae (5%), Pomona (2%),
      Castellonis (2%) and Copenhageni (0.8%). We concluded that the Leptospira spp. in
      sheep is widespread in the area of sheep farms in Maranhao state, and a risk
      factor is the animals' water source.

PMID- 24326773
TI  - Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1.
AB  - Functional pancreatic neuroendocrine tumours (PNETs) are mainly represented by
      insulinoma, which secrete insulin independent of glucose and cause hypoglycaemia.
      The major genetic alterations in sporadic insulinomas are still unknown. Here we
      identify recurrent somatic T372R mutations in YY1 by whole exome sequencing of 10
      sporadic insulinomas. Further screening in 103 additional insulinomas reveals
      this hotspot mutation in 30% (34/113) of all tumours. T372R mutation alters the
      expression of YY1 target genes in insulinomas. Clinically, the T372R mutation is
      associated with the later onset of tumours. Genotyping of YY1, a target of mTOR
      inhibitors, may contribute to medical treatment of insulinomas. Our findings
      highlight the importance of YY1 in pancreatic beta-cells and may provide
      therapeutic targets for PNETs. 

PMID- 24326774
TI  - Monolayer contact doping of silicon surfaces and nanowires using organophosphorus
      compounds.
AB  - Monolayer Contact Doping (MLCD) is a simple method for doping of surfaces and
      nanostructures(1). MLCD results in the formation of highly controlled, ultra
      shallow and sharp doping profiles at the nanometer scale. In MLCD process the
      dopant source is a monolayer containing dopant atoms. In this article a detailed
      procedure for surface doping of silicon substrate as well as silicon nanowires is
      demonstrated. Phosphorus dopant source was formed using tetraethyl
      methylenediphosphonate monolayer on a silicon substrate. This monolayer
      containing substrate was brought to contact with a pristine intrinsic silicon
      target substrate and annealed while in contact. Sheet resistance of the target
      substrate was measured using 4 point probe. Intrinsic silicon nanowires were
      synthesized by chemical vapor deposition (CVD) process using a vapor-liquid-solid
      (VLS) mechanism; gold nanoparticles were used as catalyst for nanowire growth.
      The nanowires were suspended in ethanol by mild sonication. This suspension was
      used to dropcast the nanowires on silicon substrate with a silicon nitride
      dielectric top layer. These nanowires were doped with phosphorus in similar
      manner as used for the intrinsic silicon wafer. Standard photolithography process
      was used to fabricate metal electrodes for the formation of nanowire based field
      effect transistor (NW-FET). The electrical properties of a representative
      nanowire device were measured by a semiconductor device analyzer and a probe
      station. 

PMID- 24326775
TI  - Quantum effects in the case of (6)Li+ and (7)Li+ ions evolving in a neutral (6)Li
      gas at a wide range of temperatures.
AB  - This work deals with the quantum-mechanical calculation of the temperature
      dependent mobility of ionic lithium atoms diffusing in their parent gas. The
      computation of the quantal phase shifts in connection with the gerade and
      ungerade potential-energy curves, through which Li(+) approaches Li(2s), leads to
      the computation of the charge-transfer and diffusion cross sections. The behavior
      of the coefficients of diffusion and mobility with temperature is also examined.
      Throughout this work, the isotopic effects in the (6)Li(+)-(6)Li and (7)Li(+)
      (6)Li collisions are emphasized. 

PMID- 24326776
TI  - Professional Talk: How Middle Managers Frame Care Workers as Professionals.
AB  - This paper examines how middle managers in the long term care sector use the
      discourse of professionalism to create 'appropriate' work conduct of care
      workers. Using Watson's concept of professional talk, we study how managers in
      their daily work talk about professionalism of vocationally skilled care workers.
      Based on observations and recordings of mundane conversations by middle managers,
      we found four different professional talks that co-exist: (1) appropriate looks
      and conduct, (2) reflectivity about personal values and 'good' care, (3)
      methodical work methods, (4) competencies. Jointly, these professional talks
      constitute an important discursive resource for middle managers to facilitate
      change on the work floor. Change involves the reconfiguration of care work and
      different managerial-worker relations. Middle managers use professional talks in
      both enabling and disenabling ways vis-a-vis care workers. Based on these
      findings, we suggest a more nuanced portrayal of the relationship between
      managers and professionals. Rather than being based on an intrinsic opposition,
      i.e. 'managers versus professionals', this relationship is flexibly reconstructed
      via professional talk. 

PMID- 24326777
TI  - Optimized delivery system achieves enhanced endomyocardial stem cell retention.
AB  - BACKGROUND: Regenerative cell-based therapies are associated with limited
      myocardial retention of delivered stem cells. The objective of this study is to
      develop an endocardial delivery system for enhanced cell retention. METHODS AND
      RESULTS: Stem cell retention was simulated in silico using 1- and 3-dimensional
      models of tissue distortion and compliance associated with delivery. Needle
      designs, predicted to be optimal, were accordingly engineered using nitinol, a
      nickel and titanium alloy displaying shape memory and superelasticity.
      Biocompatibility was tested with human mesenchymal stem cells. Experimental
      validation was performed with species-matched cells directly delivered into
      Langendorff-perfused porcine hearts or administered percutaneously into the
      endocardium of infarcted pigs. Cell retention was quantified by flow cytometry
      and real-time quantitative polymerase chain reaction methodology. Models,
      computing optimal distribution of distortion calibrated to favor tissue
      compliance, predicted that a 75 degrees -curved needle featuring small-to-large
      graded side holes would ensure the highest cell retention profile. In isolated
      hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold
      superior stem cell retention compared with a standard needle. In the setting of
      chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a
      37.7+/-7.1% versus 10.0+/-2.8% retention achieved with a traditional needle
      without effect on biocompatibility or safety. CONCLUSIONS: Modeling-guided
      development of a nitinol-based curved needle delivery system with incremental
      side holes achieved enhanced myocardial stem cell retention.

PMID- 24326778
TI  - HS-173, a novel PI3K inhibitor, attenuates the activation of hepatic stellate
      cells in liver fibrosis.
AB  - Hepatic stellate cells (HSCs) are the primary source of matrix components in
      liver disease such as fibrosis. Phosphatidylinositol 3-kinase (PI3K) signaling in
      HSCs has been shown to induce fibrogenesis. In this study, we evaluated the anti
      fibrotic activity of a novel imidazopyridine analogue (HS-173) in human HSCs as
      well as mouse liver fibrosis. HS-173 strongly suppressed the growth and
      proliferation of HSCs and induced the arrest at the G2/M phase and apoptosis in
      HSCs. Furthermore, it reduced the expression of extracellular matrix components
      such as collagen type I, which was confirmed by an in vivo study. We also
      observed that HS-173 blocked the PI3K/Akt signaling pathway in vitro and in vivo.
      Taken together, HS-173 suppressed fibrotic responses such as cell proliferation
      and collagen synthesis by blocking PI3K/Akt signaling. Therefore, we suggest that
      this compound may be an effective therapeutic agent for ameliorating liver
      fibrosis through the inhibition of PI3K signaling. 

PMID- 24326779
TI  - Clinical results and second-look arthroscopic findings after treatment with
      adipose-derived stem cells for knee osteoarthritis.
AB  - PURPOSE: In the present study, the clinical outcomes and second-look arthroscopic
      findings of intra-articular injection of stem cells with arthroscopic lavage for
      treatment of elderly patients with knee osteoarthritis (OA) were evaluated.
      METHODS: Stem cell injections combined with arthroscopic lavage were administered
      to 30 elderly patients (>=65 years) with knee OA. Subcutaneous adipose tissue was
      harvested from both buttocks by liposuction. After stromal vascular fractions
      were isolated, a mean of 4.04 * 10(6) stem cells (9.7 % of 4.16 * 10(7) stromal
      vascular fraction cells) were prepared and injected in the selected knees of
      patients after arthroscopic lavage. Outcome measures included the Knee Injury and
      Osteoarthritis Outcome Scores, visual analog scale, and Lysholm score at
      preoperative and 3-, 12-, and 2-year follow-up visits. Sixteen patients underwent
      second-look arthroscopy. RESULTS: Almost all patients showed significant
      improvement in all clinical outcomes at the final follow-up examination. All
      clinical results significantly improved at 2-year follow-up compared to 12-month
      follow-up (P < 0.05). Among elderly patients aged >65 years, only five patients
      demonstrated worsening of Kellgren-Lawrence grade. On second-look arthroscopy,
      87.5 % of elderly patients (14/16) improved or maintained cartilage status at
      least 2 years postoperatively. Moreover, none of the patients underwent total
      knee arthroplasty during this 2-year period. CONCLUSION: Adipose-derived stem
      cell therapy for elderly patients with knee OA was effective in cartilage
      healing, reducing pain, and improving function. Therefore, adipose-derived stem
      cell treatment appears to be a good option for OA treatment in elderly patients.
      LEVEL OF EVIDENCE: Therapeutic case series study, Level IV.

PMID- 24326780
TI  - Quadriceps corticomotor excitability following an experimental knee joint
      effusion.
AB  - PURPOSE: Deficits in quadriceps strength and voluntary activation are common
      following knee injury. These deficits are hypothesized to generate from a neural
      level, however, it remains unclear how corticomotor pathways are affected
      following acute injury. The purpose of this investigation was to examine whether
      corticomotor alterations of the quadriceps were present following a simulated
      knee joint injury using an experimental effusion model. METHODS: Participants
      completed two testing sessions, an experimental knee effusion and control
      session, separated by 7 days. The central activation ratio was used to assess
      change in quadriceps activation. Corticomotor excitability was assessed pre- and
      post-intervention via active motor thresholds (AMTs) and motor evoked potentials
      (MEPs) normalized to maximal muscle responses. MEPs were assessed at different
      percentages of AMT, and associated slopes between these percentages were
      analysed. Paired-sample t tests were performed on percentage change scores
      calculated from pre-intervention outcome measures to assess change in
      corticomotor excitability and changes in the slope of MEP values as percentage of
      AMT increased. RESULTS: Quadriceps activation significantly decreased during the
      effusion session. AMT and MEP change scores were not different between effusion
      and control conditions. No substantial differences were found in slope between
      any percentages of AMT. CONCLUSIONS: An experimental knee effusion did not induce
      changes in corticomotor excitability. Further research is needed to understand
      how corticomotor pathways are affected following joint injury. Corticomotor
      excitability alterations may not be the cause of acute changes in neuromuscular
      activation following joint effusion. Future research should determine whether
      clinically altering corticomotor excitability will improve physical function.
      LEVEL OF EVIDENCE: II.

PMID- 24326781
TI  - The effect of cleaning substances on the surface of denture base material.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of substances used
      for hygienic cleaning of dentures on the surface of the denture base material.
      MATERIAL AND METHODS: Meliodent Heat Cure (Heraeus-Kulzer, Germany) heat
      polymerized acrylic resin was used to produce plates with all the characteristics
      of removable denture bases (subsequently, "plates"). Oral-B Complete toothbrushes
      of various brush head types were fixed to a device that imitated tooth brushing
      movements; table salt and baking soda (frequently used by patients to improve
      tooth brushing results), toothpaste ("Colgate Total"), and water were also
      applied. Changes in plate surfaces were monitored by measuring surface reflection
      alterations on spectrometry. Measurements were conducted before the cleaning and
      at 2 and 6 hours after cleaning. RESULTS: No statistically significant
      differences were found between the 3 test series. All 3 plates used in the study
      underwent statistically significant (p<0.05 changed)--the reflection became
      poorer. The plates were most affected by the medium-bristle toothbrush with
      baking soda--the total reflection reduction was 4.82 +/- 0.1%; among toothbrushes
      with toothpaste, the hard-type toothbrush had the greatest reflection-reducing
      effect--4.6 +/- 0.05%, while the toothbrush with table salt inflicted the least
      damage (3.5 +/- 0.16%) due to the presence of rounded crystals between the
      bristles and the resin surface. Toothbrushes with water had a uniform negative
      effect on the plate surface - 3.8 9 +/- 0.07%. CONCLUSIONS: All substances used
      by the patients caused surface abrasion of the denture base material, which
      reduced the reflection; a hard toothbrush with toothpaste had the greatest
      abrasive effect, while soft toothbrushes inflicted the least damage.

PMID- 24326782
TI  - Analysis of the pentafecta learning curve for laparoscopic radical prostatectomy.
AB  - PURPOSE: Laparoscopic radical prostatectomy (LRP) has a long learning curve;
      however, little is known about the pentafecta learning curve for LRP. We analysed
      the learning curve for a fellowship trained surgeon with regard to the pentafecta
      with up to 6-year follow-up. METHODS: A retrospective review was performed in 550
      cases, by dividing these cases into 11 groups of 50 patients. Outcomes analysed
      were the following: (1) the pentafecta (complication rate, positive surgical
      margin (PSM) rate, continence, potency and biochemical recurrence); (2) operative
      time and blood loss; and (3) overall pentafecta attainment. RESULTS: The mean
      complication rate for the entire series was 9 %; this plateaued after 150 cases.
      The overall PSM rate for the series was 23.5 %, 16.3 % for pT2 and 40.5 % for
      pT3. PSM plateaued after 200 cases. Excluding the first 100 cases, the overall
      PSM rate for pT2 was 10.9 % and 37.8 % for pT3. The continence rate stabilised
      after approximately 250 cases. The rate of male sling/artificial urinary
      sphincter plateaued after 200 cases. The potency learning curve continues to
      improve after 250 cases of nerve-sparing (ns) endoscopic extraperitoneal radical
      prostatectomy (EERPE) as does the pentafecta learning curve which closely follows
      the pattern of the potency learning curve. The last group of nsEERPE achieved
      pentafecta in 63 %. CONCLUSION: This study shows multiple learning curves: an
      initial for peri-operative outcomes, then stabilisation of oncologic outcomes and
      the final for stabilisation of functional outcomes. In this series over 250 cases
      were required to achieve the learning curve.

PMID- 24326783
TI  - The relationship between neutrophil/lymphocyte ratio and infarct-related artery
      patency before mechanical reperfusion in patients with ST-elevation myocardial
      infarction.
AB  - OBJECTIVES: Reduced baseline coronary flow in an infarct-related artery (IRA)
      before a primary percutaneous coronary intervention (PPCI) increases mortality in
      patients with ST-elevation myocardial infarction (STEMI). Increased
      neutrophil/lymphocyte (N/L) ratio has been linked to poor clinical outcomes in
      patients with STEMI. We investigated whether the N/L ratio, as measured at
      admission, was associated with IRA patency before mechanical reperfusion in
      patients with STEMI undergoing PPCI. PATIENTS AND METHODS: A total of 404
      patients who had undergone PPCI on a single culprit artery were enrolled in this
      study. According to thrombolysis in myocardial infarction (TIMI) flow grade in
      the IRA before PPCI, the study population was divided into two groups as TIMI 0
      or 1 group (occluded IRA) and TIMI 2 or 3 group (patent IRA). RESULTS: The N/L
      ratios were found to be significantly higher in the TIMI flow 0/1 group when
      compared with the TIMI flow 2/3 group (6.08+/-3.94 vs. 4.01+/-2.87, P=0.001). The
      absence of early IRA patency was associated with higher Syntax score, mean
      platelet volume, creatine kinase-myocardial band, and troponin T levels
      (P=0.0001, P=0.03, P<0.001, and P=0.004, respectively), and lower left
      ventricular ejection fraction (P=0.02). Multivariate logistic regression analysis
      showed that the N/L ratio and Syntax score were independent predictors of IRA
      patency (odds ratio: 1.89, 95% confidence interval: 1.82-1.98; odds ratio=2.80,
      95% confidence interval: 1.75-3.86, respectively; P=0.001). CONCLUSION: The N/L
      ratio has been found to be associated independently with early IRA patency before
      PPCI in patients who have undergone PCI for STEMI. This simple and cheap
      parameter can provide useful information on the related risk evaluation in these
      patients.

PMID- 24326784
TI  - Coronary artery spasm and thyrotoxicosis: the best index is that of suspicion.

PMID- 24326785
TI  - C1q nephropathy in children: clinical characteristics and outcome.
AB  - BACKGROUND: C1q nephropathy has been suggested as a separate disease entity. C1q
      positivity has also been described in association with nephrotic syndrome (NS) as
      a potential marker for worse outcome. The aims of this study were to describe the
      clinical characteristics, laboratory parameters and outcomes of 35 children whose
      renal histology revealed predominant mesangial C1q deposition and to investigate
      if the experience at our institution supports the above hypothesis. METHOD:
      Clinical and pathological characteristics of all children whose kidney biopsies
      showed positive C1q staining were retrospectively recorded. The outcome of
      children with minimal change nephrotic syndrome (MCNS) and predominant mesangial
      C1q deposition based on C1q staining was compared with that of a concurrent group
      of children with MCNS with no such immune staining. RESULTS: The median age of
      the patient cohort was 4.5 years (range 6 months to 16 years), 69 % were boys and
      88 % presented with nephrotic syndrome (NS). Children with C1q staining and MCNS
      had more relapses (p = 0.001) and shorter relapse-free periods (p = 0.033) than
      those with negative immunostaining, but the long-term outcomes were similar in
      both groups. CONCLUSION: Our data do not support C1q nephropathy as a separate
      diagnostic category. Children with MCNS and mesangial C1q deposition (staining)
      showed more relapses but no difference in long term renal outcome.

PMID- 24326786
TI  - N-acetyl-cysteine is associated to renal function improvement in patients with
      nephropathic cystinosis.
AB  - BACKGROUND: Nephropathic cystinosis is an autosomal recessive systemic severe
      disease characterized by intralysosomal cystine storage. Cysteamine is an
      essential component of treatment. There is solid evidence that cystine
      accumulation itself is not responsible for all abnormalities in cystinosis; there
      is also a deficiency of glutathione in the cytosol. Patients with cystinosis can
      be more susceptible to oxidative stress. CASE-DIAGNOSIS/TREATMENT: The patient
      cohort comprised 23 cystinosis patients (16 males) aged <18 years (mean age 8.0
      +/- 3.6 years) with chronic kidney disease class I-IV with good adherence to
      treatment, including cysteamine. Oxidative stress was evaluated based on the
      levels of serum thiobarbituric acid-reactive substances (TBARS), and renal
      function was evaluated based on serum creatinine and cystatin C levels and
      creatinine clearance (Schwartz formula). N-Acetylcysteine (NAC), an antioxidant
      drug was given to all patients for 3 months (T1) at 25 mg/kg/day divided in three
      doses per day. The measured values at just before the initiation of NAC treatment
      (T0) served as the control for each patient. RESULTS: Median serum TBARS levels
      at T0 and T1 were 6.92 (range 3.3-29.0) and 1.7 (0.6-7.2)  nmol/mL, respectively
      (p < 0.0001). In terms of renal function at T0 and T1, serum creatinine levels
      (1.1 +/- 0.5 vs. 0.9 +/- 0.5 mg/dL, respectively; p < 0.0001), creatinine
      clearance (69.7 +/- 32.2 vs. T1 = 78.5 +/- 33.9 mL/min/1.73 m(2), respectively; p
      = 0.006), and cystatin c level (1.33 +/- 0.53 vs. 1.15 +/- 0.54 mg/l,
      respectively; p = 0.0057) were all significantly different at these two time
      points. Serum creatinine measurements at 6 (T -6) and 3 months (T -3) before NAC
      initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were
      also evaluated. CONCLUSION: During the 3-month period that our 23 cystinosis
      patients were treated with NAC, oxidative stress was reduced and renal function
      significantly improved. No side-effects were detected. Larger and controlled
      studies are needed to confirm these findings.

PMID- 24326788
TI  - Screening blood pressure measurement in children: are we saving lives?
AB  - Blood Pressure screening in children and adolescents is currently recommended by
      several prominent medical organizations, including the American Heart
      Association, the National High Blood Pressure Education Program, the National
      Heart, Lung, and Blood Institute, the European Society of Hypertension, and the
      American Academy of Pediatrics. This practice was recently subject to intense
      scientific review by the U.S. Preventive Services Task Force. The conclusion of
      the Task Force was that "current evidence is insufficient to assess the balance
      of benefits and harms of screening for primary hypertension in asymptomatic
      children and adolescents." This commentary provides an alternate interpretation
      of current evidence for blood pressure screening in children and adolescents and
      highlights its importance as a part of routine medical care. 

PMID- 24326789
TI  - [Renal function tests in milk fed calves--reference values and influence of
      bovine neonatal pancytopenia (BNP)].
AB  - OBJECTIVES: Renal function tests were performed on 38 clinically healthy Holstein
      calves aged 1435 days, of which seven had survived bovine neonatal pancytopenia
      (BNP). The main objective was the establishment of reference values for renal
      fractional excretions (FE) of sodium (Na), potassium (K), calcium (Ca) and
      phosphate (P) in calves fed milk replacer. Additionally, it should be clarified
      whether calves suffer from permanent renal disorders as a result of BNP. MATERIAL
      AND METHODS: The fractional excretions were determined using wet chemical
      analyses of simultaneously taken urine and blood samples. Their calculation was
      based on the endogenous excretion of creatinine. RESULTS: There were no
      significant differences in the FE between calves with and without a history of
      BNP. Based on the values of all 38 calves, reference values were calculated for
      the FE indicated above, and also for the urinary gamma-glutamyltransferase
      creatinine ratio as a parameter for the damage of tubular cells. CONCLUSION: It
      has been demonstrated that age- and feeding-specific reference values for renal
      function parameters in cattle are necessary. For renal function analyses in
      calves, the nutritional supply with electrolytes has to be considered to
      differentiate the variability of electrolyte excretions due to different feeding
      regimes from renal disorders. Based on the calculated reference values for calves
      fed milk replacer, renal function disorders can be determined sensitively and
      further differentiation is possible.

PMID- 24326790
TI  - [Relationship between natal course and metabolic parameters during the peripartal
      period in cattle].
AB  - OBJECTIVE: To evaluate metabolic disorders in high-yielding cattle du- ring the
      peripartal period, the relationship between the course of the delivery and
      relevant metabolic parameters (insulin-like growth fac-tor 1 [IGF-1], cortisol
      and non-esterified fatty acids [NEFA]) were examined. MATERIAL AND METHODS: A
      total of 28 heavily pregnant cows (13 primiparous and 15 multiparous) with normal
      and difficult natal courses, respectively, were included in the study. Serum IGF
      1, NEFA and cortisol were analysed between day 14 ante partum (a. p.) and day 14
      post partum (p. p.), IGF-1 and cortisol were also determined in the newborn
      calves. RESULTS: An elevated stress situation was present for all heifers
      primarily at birth, because their serum IGF-1 levels were lower (114 +/- 11 vs
      158 +/- 28 ng/ml) while NEFA and cortisol values were higher (896 +/- 76 vs 705
      +/- 58 umol/l, p = 0.05; 6.51 +/- 1.14 vs 4.67 +/- 0.46 ng/ml, p = 0.039,
      respectively) than those of the cows. During the entire examination period,
      metabolic disorders could be found in animals with difficult birth, based on
      significantly lower IGF-1 values (p = 0.003; heifers: p < 0.001), significantly
      higher NEFA levels (at birth p = 0.05) and higher cortisol values compared to the
      animals with a normal birth. Similar to their mothers, newborn calves of heifers
      with dystocia had significantly higher cortisol (p = 0.003) at birth and lower
      IGF-1 levels (p = 0.002) p. p. compared to calves with a normal natal course.
      CONCLUSION AND CLINICAL RELEVANCE: Identification and prevention of natal
      disorders in cattle is very important, especially with regard to animal welfare
      and economics. In this study, difficult natal courses were associated with
      altered blood serum concentrations of IGF-1, NEFA and cortisol, which
      consequently reflect an elevated stress situation during the peripartal period.
      Furthermore, with regard to these results, it can be concluded that heifers with
      dystocia are affected by an increased metabolic stress situation mainly during
      the antepartal period, while multiparous cows suffer from metabolic disorders
      primarily in the period after birth.

PMID- 24326791
TI  - Watering cattle (young bulls) with brackish water--a hazard due to its salt
      content?
AB  - OBJECTIVE: The aim of this experimental study was primarily to test the effects
      and reactions of cattle offered salty water as the only source of drinking water.
      MATERIAL AND METHODS: Mineral balance studies were carried out on three bull,
      continuously fed a ration based on hay, hay cobs, barley, soybean meal and a
      vitamin/mineral supplement. The salt content of the drinking water varied between
      the trials (trials I/II/III: 0.10/5.00/10.0 g/l; town water supplemented by
      different amounts of an additive containing 95.4% sodium chloride and 4.6%
      potassium chloride). RESULTS: Rising salt concentration of the drinking water led
      to significantly higher sodium, potassium and chloride intake (sodium: trial
      I/II/III = 5.42/59.5/ 157 g/day; potassium: trials I/II/III = 108/117/121 g/day;
      chloride: trials I/II/III = 22.8/112/266 g/day) mainly caused by a significantly
      higher water intake (trials I/II/III: 21.8 +/- 2.03/30.4 +/- 3.08/41.5 +/- 5.89
      kg/day). Amounts of urine increased significantly (trials I/II/III: 3.99 +/-
      0.46/ 9.66 +/- 1.34/20.2 +/- 3.14 kg/day). The concentrations of minerals in the
      urine (sodium: trials I/II/III = 123/3729/6705 mg/kg; potassium: trials I/II/III
      = 17345/9996/ 5496 mg/kg; chloride: trials I/II/III = 2020/ 9672/11870 mg/kg) and
      faeces (sodium: trials I/II/III = 1299/6544/ 7653 mg/kg; potassium: trials
      I/II/III = 6343/3719/3490 mg/kg; chloride: trials I/II/III = 3851/4580/4693
      mg/kg) also changed significantly over time. Serum values of sodium tended to
      decrease (trials I/II/III: 142/137/137 mmol/l) within the physiological range,
      whereas those of chloride increased (trials I/II/III: 91.5/95.6/97.5 mmol/l) at
      higher salt concentrations in drinking water. The haematocrit, pH-value as well
      as urea content in blood were not affected by the higher salt intake. In balance
      trial III (highest salt load: 10.0 g/l), sodium intake of the bulls reached 0.57
      +/- 0.03 g/kg BW (~22.1 +/- 0.9 g sodium/kg dry matter feed). CONCLUSION AND
      CLINICAL RELEVANCE: An increase of salinity in drinking water up to 10 g/l--with
      otherwise harmless water quality--had no measurable negative effects on animal
      health in the investigation period and subsequent periods (total of 58 days with
      more than 5.00 g of salt per litre drinking water).

PMID- 24326787
TI  - Electrolyte abnormalities in cystic fibrosis: systematic review of the
      literature.
AB  - BACKGROUND: Cystic fibrosis per se can sometimes lead to hyponatremia,
      hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first
      documented 60 years ago and has subsequently been confirmed in single case
      reports or small case series, most of which were retrospective. However, this
      issue has not been addressed analytically. We have therefore systematically
      reviewed and analyzed the available literature on this subject. METHODS: This was
      a systematic review of the literature. RESULTS: The reports included in this
      review cover 172 subacute and 90 chronic cases of electrolyte imbalances in
      patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte
      abnormalities were mostly associated with clinically inapparent fluid volume
      depletion, mainly affected patients aged <=2.5 years, frequently tended to recur
      and often were found before the diagnosis of cystic fibrosis was established.
      Subacute presentation often included an history of heat exposure, vomiting,
      excessive sweating and pulmonary infection. History of chronic presentation, in
      contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and
      metabolic alkalosis was similar between subacute and chronic patients, with
      hyponatremia being more pronounced (P < 0.02) in subacute compared to chronic
      presentations. Subacute cases were treated parenterally; chronic ones were
      usually managed with oral salt supplementation. Retention of urea and creatinine
      was documented in 38 % of subacute cases. CONCLUSIONS: The findings of our review
      suggest that physicians should be aware that electrolyte abnormalities can occur
      both as a presenting and a recurring feature of cystic fibrosis.

PMID- 24326792
TI  - [Influence of atracurium on cardiovascular parameters in horses undergoing
      vitrectomy during general anaesthesia, and on recovery duration and quality].
AB  - OBJECTIVE: In most ocular procedures, a central position of the eye is necessary.
      This can be achieved using a deep plane of anaesthesia, locoregional blocks or
      with neuromuscular blocking agents. The aim of this study was to evaluate the
      influence of atracurium on cardiovascular parameters, and on recovery quality and
      duration in horses. MATERIAL AND METHODS: Thirty-four warmblood horses undergoing
      in total 50 vitrectomies were divided into two groups. Premedication, induction
      and maintenance were identical in all patients. After 20 minutes, horses of group
      A received atracurium (0.1 mg/kg) while in the control group (group K) the depth
      of anaesthesia was adapted to keep the bulbus in a central position. Dobutamine
      and fluids were administered to maintain the mean arterial blood pressure (MAP)
      above 70 mmHg. Cardiac output (CO), heart rate (HR), MAP, respiratory rate, end
      expiratory isoflurane concentration (ETIso) and dobutamine requirements were
      determined. Position and movement of the globe during the surgical procedure were
      scored. Time and quality of the recovery period was scored. RESULTS: Horses of
      group K required significantly higher concentrations of isoflurane (group A: 1.08
      +/- 0.1%; group K: 1.34 +/- 0.2%) and had an overall lower MAP (group A: 88.4 +/-
      10.3 mmHg; group K: 76.6 +/- 11.6 mmHg) and CO (group A: 36.9 +/- 11.7 l/min;
      group K: 28.5 +/- 7.2 l/min) but needed significantly more dobutamine (group A:
      0.37 +/- 0.17 MUg/kg/min; group K: 0.99 +/- 0.46 MUg/kg/min) compared to group A.
      Complete relaxation occurred 9.5 +/- 2.5 minutes after atracurium bolus and
      lasted for 25 +/- 7.1 minutes. The score of the bulbus position and movement was
      significantly lower in group A, resulting in a better quality for the surgical
      procedure. In group A, the recovery time to standing was significantly shorter
      (group A: 18.1 +/- 5.4 min; group K: 31.5 +/- 7.1 min), with no difference in
      quality. CONCLUSION AND CLINICAL RELEVANCE: The use of atracurium resulted in a
      better cardiovascular condition, probably because of the isoflurane-sparing
      effect. The recovery time was shorter in these horses without negative effects on
      recovery quality. No signs of residual atracurium effects were detected.

PMID- 24326793
TI  - [Relationship between residual milk and clinical mastitis in dairy cattle].
AB  - Mastitis in cattle is an infection of the mammary gland caused by infection,
      toxins and/or trauma. Currently, it is assumed that there is a correlation
      between higher amounts of residual milk and the incidence of clinical mastitis.
      The amount of residual milk can be examined using different methods. Higher
      amounts of residual milk may result from an insufficient teat condition and
      individual detachment settings of milking units. To date, scientific literature
      has already discussed the relationship between high amounts of residual milk,
      undermilking and the occurrence of clinical mastitis. The present paper reviews
      the current status of knowledge regarding residual milk and risk of mastitis. 

PMID- 24326794
TI  - Perosomus elumbis in a Holstein calf infected with bovine viral diarrhea virus.
AB  - The detection of bovine viral diarrhea virus (BVDV) in a female Holstein calf
      presented with perosomus elumbis, a congenital anomaly, is reported here. A cow
      with dystocia was evaluated and an abnormal dead calf was detected during vaginal
      examination. The calf was retrieved via caesarean section and exhibited
      abnormalities characteristic of PE, such as vertebral and pelvic malformations.
      These abnormalities were further confirmed using radiographic and necropsy
      examinations. At necropsy cerebellar hypoplasia was an additional finding, which
      is a typical lesion associated with bovine virus diarrhea (BVD). Several tissue
      samples from the calf were tested for the presence of antigens of BVDV and bovine
      herpesvirus-1 (BHV-1) by ELISA. In addition, sera samples from the dam and calf
      were tested for the presence of antibodies against BVDV, BHV-1, and bluetongue
      disease virus (BTV) using a virus neutralization assay. Results indicated that
      the calf was congenitally infected with BVDV, whereas there was no evidence for
      the presence of BHV-1 and BTV. In the dam's serum no antibodies against BVDV, BHV
      1, and BTV were detected. Even though the etiology of perosomus elumbis is
      unknown, BVDV, which causes fetal anomalies at early gestation in cows, may have
      been a contributing factor in this case. 

PMID- 24326795
TI  - [Sudden death of outdoor housed pigs caused by Clostridium novyi. A case report].
AB  - In an outdoor pig-breeding unit of the Tierpark Arche Warder e. V. (Germany), 16
      pigs of different age and sex died in October 2011. Necropsy findings revealed
      tympany, liver emphysema, subcutaneous oedema, haemopericardium, haemothorax, and
      intense gas bubble infiltrations in muscles. The stomachs were filled. The
      initial anaerobic bacteriological investigations gave negative results. In
      further analyses of tissue samples, the flagellin gene of C. novyi types A and B
      was detected using PCR. Based on the anatomical-pathological and bacteriological
      findings as well as PCR testing, a C. novyi infection was assumed to be the cause
      of the pig mortality. 

PMID- 24326796
TI  - [Skin diseases of swine].
AB  - Skin alterations can be caused by both environmental conditions and diseases of
      the organism. Some diseases may only manifest in the skin while others represent
      signs of a generalized infection. Regarding their origin, skin diseases can be
      divided into congenital, infectious, and nutritional disorders, and those
      resulting from housing scarcities. Additionally, there are skin diseases with
      unknown causes. Skin diseases in a swine herd can result in economic losses
      through decreased feed efficiency and growth rate and increased mortality. The
      knowledge of causes and symptoms as well as the selection of appropriate further
      laboratory investigations provide a valid diagnosis and enable a quick and
      effective therapy. This description of several skin diseases should provide a
      background. 

PMID- 24326797
TI  - Outcome of primary posterior sagittal anorectoplasty of high anorectal
      malformation in well selected neonates.
AB  - BACKGROUND: Conventional posterior sagittal anorectoplasty (PSARP) for high
      anorectal malformation (ARM) involves initial colostomy creation with its
      attendant complications, but primary PSARP in neonates requires no initial
      colostomy. OBJECTIVES: To report on locally adapted inclusion criteria and
      outcomes of primary PSARP in neonates in Benin City. MATERIALS AND METHODS:
      Babies who presented during the first week of life in clinically stable
      conditions, without cardiac anomaly, and had hemogram and blood chemistry within
      normal ranges, were included in this prospective study undertaken at the
      University of Benin Teaching Hospital in 2008-2011. RESULTS: Fifty children with
      ARM comprising 19 (38%) low/intermediate and 31 (62%) high anomalies were treated
      during the period. Five (10%) singletons delivered via spontaneous vaginal
      delivery at term. Aged at operation between two and seven (mean 4) days and
      comprised three males and two females (ratio 1.5:1), met the inclusion criteria
      for primary PSARP. The procedure was well tolerated by all the babies; oral
      intake was commenced on the second post-operative day with nine days median
      hospitalization duration. No mortality was recorded on six months to four years
      follow-up. Apart from minor superficial perianal surgical site infection in one
      baby which responded to antibiotics, no post-operative sepsis or breakdown of
      repair was recorded. Continence and other anal functions were found excellent
      using the modified Wingspread scoring during follow-up. CONCLUSION: These
      outcomes showed that with meticulous selection, primary PSARP in neonates was
      feasible and safe in a developing country. Multicenter studies and long-term
      follow-up are advocated World-wide.

PMID- 24326798
TI  - Awareness, knowledge and attitude on cleft lip and palate among antenatal clinic
      attendees of tertiary hospitals in Nigeria.
AB  - BACKGROUND: Adequate knowledge and awareness of cleft lip and palate (CLP)
      deformity may help to counter the negative beliefs and attitudes toward the
      condition. The objective of this study was to assess the level of awareness,
      knowledge and attitude of women attending antenatal clinics about CLP. MATERIALS
      AND METHODS: A cross-sectional descriptive study with the aid of a structured
      interview administered questionnaire was conducted among 200 women attending
      antenatal clinics in three Federal Government Teaching Hospitals in the Northern
      and Southwestern regions of Nigeria. The main outcome measure was the level of
      awareness and the mean cumulative knowledge score. RESULTS: The mean age of the
      subjects was 28.9 +/- 5.1 years (age range: 16-42 years). Half of the women
      (50.5%) reported that they had seen or heard about CLP. The mean cumulative
      knowledge score was 6.9, with only 19.8% having adequate knowledge. Many
      respondents had neither read an article on CLP nor participated in any public
      enlightenment program, and 31.5% indicated that they would like to know more
      about the condition. Level of educational attainment had a statistically
      significant effect on the level of awareness and knowledge on CLP, as more
      educated respondents tend to be more aware and knowledgeable ( P < 0.001).
      CONCLUSION: There is need for increased public enlightenment/health education to
      increase awareness and subsequently help develop more positive attitudes toward
      children with CLP. Such programs should include distribution of pamphlets on CLP
      at clinics, especially antenatal clinics, media campaigns on radio, TV and
      newspaper as well as establishment of cleft support groups by the relevant
      governmental and professional organizations.

PMID- 24326799
TI  - Oral misoprostol in the prevention of uterine bleeding after surgical evacuation
      of first trimester abortion: a comparative study of three uterotonic agents.
AB  - OBJECTIVE: This comparative study was aimed at determining the effectiveness of
      oral Misoprostol compared with intravenous Ergometrine and intravenous Oxytocin
      in reducing vaginal bleeding following surgical evacuation for first trimester
      abortions. MATERIALS AND METHODS: This was a single-blind placebo-controlled
      study in which patients with first trimester uncomplicated abortions were divided
      into three groups using computer-generated randomization table. The first group
      was administered oral Misoprostol, the second group had intravenous Ergometrine,
      and the third group was administered intravenous Oxytocin. The uterotonic agents
      were administered before the surgical evacuation was carried out. RESULTS: There
      was statistically significant reduction in blood loss after the evacuation in the
      Misoprostol group ( P < 0.000). There was also significant reduction in the
      number of days of bleeding in the Misoprostol group (2.00 +/- 0.86) compared with
      4.43 +/- 0.92 and 4.64 +/- 1.06 days in the Ergometrine and Oxytocin groups,
      respectively ( P < 0.000). There were, however, more gastrointestinal side
      effects in the Misoprostol and Ergometrine groups (60.7% and 57.1%, respectively)
      compared with the Oxytocin group. CONCLUSION: Oral Misoprostol appeared to
      demonstrate superior efficacy in reducing uterine bleeding after surgical
      evacuation, compared to the other commonly used uterotonic agents.

PMID- 24326800
TI  - Pediatric cataract surgery in Madagascar.
AB  - BACKGROUND: Cataract is the main cause of blindness among children in Africa,
      having replaced vitamin A deficiency and measles. The management of childhood
      cataract in Africa, especially francophone countries, is inadequate. AIMS AND
      OBJECTIVE: The objective is to study the age at presentation of children
      diagnosed with cataract, their visual outcomes, and follow-up patterns after
      surgery in Madagascar. MATERIALS AND METHODS: This was a retrospective case
      series of children operated on for cataract in one of the busiest eye hospitals
      in Madagascar between September 1999 and July 2009. Data were obtained from
      theater logs and patient case notes and entered in a Microsoft Excel spreadsheet.
      Data entry was carried out using Microsoft Excel and analysis using Intercooled
      Stata version 9.0. Student t-test and Pearson's Chi-square were used to test
      associations where appropriate. RESULTS: A total of 60.5 percent of the 86
      children operated on during the study period were boys. The mean age at
      presentation was 6.9 years (+/-SD 4.3) for congenital cataract, 13.1 years (+/-SD
      2.9) for developmental cataract and 9.4 years (+/-SD 4.0) for traumatic cataract.
      A total of 36 children (41.9%) came back for follow-up, while 72 children (83.7%)
      were lost to follow-up 5 weeks after surgery. The mean follow-up period was 5
      weeks (+/-SD 17.9). Children, who were brought back for follow-up were younger
      than those who were not. Although 64 (74.4%) of children had refraction during
      their encounters with the eye care facility, only 3 (3.5%) were provided with
      glasses. At last documented follow-up, 2.7% of the children had 6/18 vision or
      better. CONCLUSIONS: In Madagascar, presentation for congenital and developmental
      cataract is very late, visual outcome poor and follow-up inadequate. There is an
      urgent need for a childhood blindness program to effectively deal with pediatric
      cataract, an avoidable cause of blindness and visual disability in children on
      the island nation.

PMID- 24326801
TI  - Non-third molar related pericoronitis in a sub-urban Nigeria population of
      children.
AB  - BACKGROUND: The study will report on the prevalence, clinical presentation,
      diagnosis, and management of non-third molar related pericoronitis seen in
      children below the age of 15 years who report at the Pediatric Dental Clinic,
      Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife over a 41/2 year
      period. MATERIALS AND METHODS: This is a prospective study of cases of
      pericoronitis affecting any tooth exclusive of the third molar diagnosed in the
      pediatric dentistry out-patient clinic in Obafemi Awolowo University Teaching
      Hospitals Complex, Ile-Ife between January 2008 and June 2012. Pericoronitis was
      diagnosed using the criteria described by Howe. Information on age, sex, history
      malaria fever, upper respiratory diseases, tonsillitis, and evidence of
      immunosuppression were taken. Radiographs were taken in all cases to rule out
      tooth impaction and information on treatment regimen was also collected. RESULTS:
      The prevalence of non-third molar related pericoronitis was 0.63%. More females
      (63.6%) were affected. Chronic pericoronitis was the most common presentation
      (73.3%). No case was reported in the primary dentition and the premolar. No case
      was associated with tooth impaction and the tooth most affected was the lower
      right second permanent molar (35.7%). Bilateral presentation was seen in 36.4%
      patients. Herpetic gingivostomatitis was reported in association with one case.
      Chronic pericoronitis resolved within 3 days of management with warm saline mouth
      bath (WSMB) and analgesics, while acute/subacute resolved within 10 days of
      management with antibiotics, analgesics, and WSMB. CONCLUSIONS: The prevalence of
      non-third molar related pericoronitis is the low. The most prevalence type is
      chronic pericoronitis affecting the lower right second permanent molar.

PMID- 24326802
TI  - Facial nerve palsy: analysis of cases reported in children in a suburban hospital
      in Nigeria.
AB  - AIM: The study describes the epidemiology, treatment, and treatment outcomes of
      the 10 cases of facial nerve palsy seen in children managed at the Obafemi
      Awolowo University Teaching Hospitals Complex, Ile-Ife over a 10 year period. It
      also compares findings with report from developed countries. METHODOLOGY: This
      was a retrospective cohort review of pediatric cases of facial nerve palsy
      encountered in all the clinics run by specialists in the above named hospital. A
      diagnosis of facial palsy was based on International Classification of Diseases,
      Ninth Revision, Clinical Modification codes. Information retrieved from the case
      note included sex, age, number of days with lesion prior to presentation in the
      clinic, diagnosis, treatment, treatment outcome, and referral clinic. FINDINGS:
      Only 10 cases of facial nerve palsy were diagnosed in the institution during the
      study period. Prevalence of facial nerve palsy in this hospital was 0.01%. The
      lesion more commonly affected males and the right side of the face. All cases
      were associated with infections: Mainly mumps (70% of cases). Case management
      include the use of steroids and eye pads for cases that presented within 7 days;
      and steroids, eye pad, and physical therapy for cases that presented later. All
      cases of facial nerve palsy associated with mumps and malaria infection fully
      recovered. The two cases of facial nerve palsy associated with otitis media only
      partially recovered. CONCLUSION: Facial nerve palsy in pediatric patients is more
      commonly associated with mumps in the study environment. Successes are recorded
      with steroid therapy.

PMID- 24326803
TI  - Cardiac arrest during anesthesia at a university Hospital in Nigeria.
AB  - BACKGROUND: We assessed the incidence and outcomes of cardiac arrest during
      anesthesia in the operating room at our university hospital. A previous study on
      intraoperative cardiac arrests covered a period from 1994-1998 and since then;
      anesthetic personnel, equipment, and workload have increased remarkably.
      MATERIALS AND METHODS: After obtaining institutional ethics approval, we
      retrospectively reviewed patients' hospital records such as anesthetic charts and
      register and ICU admission charts between 1 st July 2005 and 30 th June 2010. The
      cardiac arrests encountered during anesthesia was identified from anesthetic
      charts and followed-up in the intensive care unit (ICU) for the first 24 h
      postoperatively. We consider that cardiac arrest occurred in any patient under
      anesthesia with asystole or ventricular fibrillation requiring cardiac
      compression or electrical defibrillation. We define recovery as an alive and non
      comatose patient 24-h after the cardiac arrest. RESULTS: During the study period,
      a total of 12,143 surgeries were done; the median age of all the patients was 30
      years (range: 1 day-119 years). A total of 31 cardiac arrests identified
      (frequency 25.5:10,000; 95% confidence interval (CI) 17.7-35.8) out of which 17
      were nonfatal. Mortality related to anesthesia was 11.5:10,000 (95% CI 6.5-18.9).
      The median age of patients with cardiac arrests was 39 years (range: 2 months-78
      years). Overall, 80.7% cardiac arrests occurred in the American Society of
      Anesthesiologists' (ASA) physical status 3-5. Cardiothoracic and neurosurgical
      operations accounted for 54.8% of the total cardiac arrests. The known risk
      factors identified among those who had cardiac arrest were, ASA physical status 3
      5 (80.7%), procedures performed out-of-work hours (60%), and manually ventilating
      patients during general anesthesia (39%). CONCLUSION: Cardiac arrest during
      anesthesia is higher in poor risk patients (ASA 3-5) who are manually ventilated
      under general anesthesia and operated during out-of-work hours.

PMID- 24326804
TI  - Comparison of chemotherapy and hematopoietic stem cell transplantation pre and
      postterm DMFT scores: a preliminary study.
AB  - AIMS: Chemotherapy is frequently used as a conditioning regimen to destroy
      malignant marrow cells before transplantation. Xerostomia, dysphagia, altered
      taste perception, mucositis, soft-tissue ulceration, and infection are common
      adverse oral effects of chemotherapy. The study was aimed to compare decayed,
      missing, filled teeth (DMFT) scores before and after hematopoietic stem cell
      transplantation (HSCT) and chemotherapy. MATERIALS AND METHODS: Thirty-six
      patients undergoing HSCT were included in the study. A pre-HSCT dental treatment
      protocol was implemented that consisted of restoration of all active carious
      lesions, treatment of periodontal infections, and extraction of all teeth with
      advanced periodontal disease. Upon completion of dental treatment, the importance
      of rigorous and effective oral hygiene was reemphasized, and patients were
      recalled 6 months later. DMFT scores were calculated prior to the initiation of
      HSCT treatment and 6 months after transplantation. STATISTICAL ANALYSIS USED:
      Regression analysis was used to evaluate the effects of HSCT and chemotherapy on
      DMFT scores. RESULTS: Wilcoxon T test showed a statistically significant
      difference in DMFT scores before and after HSCT ( P < 0.001). CONCLUSIONS: DMFT
      scores were found to increase after chemotherapy and HSCT, suggesting that the
      risk of infection is higher among HSCT patients when compared to other
      individuals. The results emphasize the need for dental examinations as an
      integral part of examination and treatment planning for patients undergoing HSCT
      and chemotherapy.

PMID- 24326805
TI  - An in vitro study of the effect of design of repair surface on the transverse
      strength of repaired acrylic resin using autopolymerizing resin.
AB  - STATEMENT OF PROBLEM: The fracture of complete denture is a common occurrence in
      the field of prosthodontics. Often if all other criteria are met such as good
      aesthetics, occlusion, and functionality; denture repair is acceptable. Once
      denture fractures, we would want the joint surface strength to be as good as
      original. PURPOSE: The purpose of this study was to determine the effect of
      different repair surface design on the transverse strength of repaired acrylic
      denture resin. MATERIALS AND METHODS: Sixty specimens of heat-cured acrylic resin
      of dimension 65 mm * 20 mm * 2.5 mm were prepared using a special die. Transverse
      strength of 15 samples was calculated which serves as a control group. Three
      different types of joint surface contours were prepared each having 15 samples
      each as butt, round, and rabbet joint. Transverse strength of three joint
      contours was then compared with control group and also they were compared with
      each other and result was statistically analyzed with one-way analysis of
      variance (ANOVA) and Post-hoc ANOVA Tukey's HSD test at 5% level of significance.
      Z-test of proportion was also done for types of failures. RESULT: Transverse
      strength of original specimen was higher than that of repaired specimens.
      Transverse strength of round joint was higher than the butt and rabbet joint.
      CONCLUSION: Methods of repair have significant effect on strength of repaired
      denture. Round joint design of repair technique was far superior.

PMID- 24326806
TI  - Treatment of unilateral giant fibroadenoma by breast reduction skin incision: the
      inverted "T" technique.
AB  - BACKGROUND: Giant fibroadenoma (GFA) has been defined as fibroadenoma greater
      than 5 cm in it's the widest diameter and/or weighing more than 500 g. A benign
      lesion, its size also raises the possibility of malignancy requiring
      differentiation from a malignant breast disease. When unilateral GFA presents
      with a severe breast asymmetry, due to its size, it is not correctable by simple
      enucleation alone. Postoperative asymmetry from volume and ptosis disparity
      results, which needs to be addressed at the primary surgery. The inverted "T"
      technique, which is effective in volume reduction and ptosis correction in breast
      hypertrophy, can be applied in the treatment of unilateral GFA. AIM: This is a
      retrospective review of all GFA treated by inverted "T" method. MATERIALS AND
      METHODS: A retrospective review was carried out on all patients with GFA treated
      by inverted "T" skin pattern method over a period of 20 years (January 1988 to
      December 2007). The procedures were carried out at the University of Nigeria
      Teaching Hospital and the National Orthopedic Hospital, Enugu. Information, which
      included patients' demographics, pre-operative assessment, operative findings and
      outcome of surgery were obtained from the case files of the patients. The degree
      of ptosis was recorded for each patient. Diagnosis of GFA was made after clinical
      evaluation and pre-operative tissue biopsy. Immediate results of treatment were
      based on the patients' satisfaction, visual assessment of symmetry of size of
      breasts, correction of ptosis and position of nipple areola complex (NAC).
      RESULTS: A total of 27 patients underwent inverted "T" technique for excision of
      GFA in their breasts. Their average age was 17.5 years (range 12-25 years) delay
      in presentation ranged from 2 months to 15 months. In 16 patients (59.2%), the
      left breast was involved in GFA whilst the tumor occurred on the right breast in
      11 (40.7%). The tumor weighed on the average 1500 g (range 655-2200 g). Average
      diameter of the tumor was 15 cm (range 12-20 cm). All quadrants of the breasts
      were involved at presentation. The inferior glandular pedicle bearing the NAC was
      used in all patients. The length of the pedicle ranged from 8 cm to 14 cm whilst
      the width ranged from 6 cm to 8 cm. Lactation was reported by three patients who
      went on to successfully breast feed. Complications were minimal. Most were minor
      wound healing problems and minor breast asymmetry. Epidermolysis in 2,
      hypertrophic scar in 6,minor breast asymmetry in 3 and delayed healing at the "T"
      junction in the inframammary fold in 4 were the common complications. All
      patients were satisfied with the result obtained. CONCLUSION: In GFA with a
      significant breast asymmetry, excision through inverted "T" technique was
      successful in achieving postoperative symmetry with the opposite breast in these
      patients. Complications were minimal.

PMID- 24326807
TI  - Pattern of presentation of oral health conditions by children at University of
      Nigeria Teaching Hospital, Enugu: a retrospective study.
AB  - AIM: The study aimed to determine the pattern of occurrence of oral conditions
      among children that attended the Child Dental Health clinic of the University of
      Nigeria Teaching Hospital (UNTH), Enugu over a 45 months period. MATERIALS AND
      METHODS: Clinical records of 305 patients, aged 3 days to 16 years, who attended
      the Child Dental Health Clinic of the UNTH from April 2008 to December 2011 were
      retrieved and analyzed. RESULTS: Out of a total of 305 children who visited the
      Child Dental Health Clinic within this period, there were 148 (48.5%) males and
      157 (51.5%) females. The ages ranged from 3 days to 16 years with a mean age of
      9.05 years, only 4.6% made asymptomatic visit while 95.4% made symptomatic visit.
      68.2% had caries and its sequeale, with no significant difference across the
      gender ( P = 1.472). Nearly 91.1% had periodontal diseases, with a significant
      difference noted ( P = 0.020) 2% had tooth developmental anomalies, 10.5% had
      traumatic dental injuries, 12.1% had malocclusion and other esthetic problems,
      15.1% had other oral pathologies, 14.4% had abnormalities of tooth eruption.
      CONCLUSION: A significant 95.4% of the children made symptomatic visit.
      Periodontal disease was the most prevalent finding followed by dental caries.
      There is an urgent need to increase dental health awareness among children
      through school based continuing dental education program and also among other
      pediatric care givers such as parents, teachers, and pediatricians.

PMID- 24326808
TI  - Early results of two methods of posterior spinal stabilization in Nigerians.
AB  - BACKGROUND: In this study, early outcomes of the spinous process wiring with
      vertical strut (SPWVS) were compared with that of standard pedicle screw and rod
      (PSR) in our patients. MATERIALS AND METHODS: We obtained patients' bio-data,
      diagnosis, investigations, cost of implant, operative circumstances,
      complications, and outcomes from clinical documentation. Outcome measures,
      including postoperative infection and persistent/recurrent instabilities, implant
      related problems, operative blood loss and time and cost, were compared in the
      two groups of patients. RESULTS: Forty one (M:F-0.9:1) patients had PSR and 35
      (M:F-2.2:1) had SPWVS. There was no difference in the occurrence of post
      operative instability ( P = 0.630), surgical site infection ( P >= 0.416),
      neurological deficits ( P >= 0.461) and implant related complications ( P >=
      0.461) in the two groups of patients. Cost of implant in the PSR group range from
      N138,000 (for 2 level fusion) (1USD = N159) to N246,000 (for 4 level fusion) with
      an average of N192,000 (Standard deviation [SD] N44,090.81) depending on the
      number of level fused while the cost of implant for SPWVS was N8,000 irrespective
      of the number of level of fusion being carried out ( P = 0.000). Mean estimated
      blood loss intra-operatively was higher for PSR (761.33 [SD 396.24] ml) than
      SPWVS (524.58 [SD 504.70] ml) ( P = 0.005). Mean operation time was 397.17 (SD
      122.183) min and 249.44 (SD 130.31) min PSR and SPWVS ( P = 0.000). CONCLUSION:
      SPWVS appears to be a good alternative to PSR, especially in our resource limited
      environment, in view of similar post-operative infection rate, implant
      complication, stability and post-operative neurological deterioration as well as
      shorter operation time, less estimated blood loss and much cheaper cost of
      implant in the former.

PMID- 24326809
TI  - Effect of the number of portal area on modified histological activity index of
      viral hepatitis and histological findings.
AB  - AIM: Viral hepatitis is one of the most important causes of chronic hepatitis.
      Liver biopsy is used to verify clinical diagnosis and to evaluate
      necroinflammation and fibrosis. Biopsy is the guide for therapy and can be
      performed also after treatment to assess the effect of therapy on liver. This
      paper aimed to explore histopathological characteristics of biopsy samples, which
      had been referred to our department with the clinical diagnosis of chronic viral
      hepatitis, in reference to Ishak Modified Hepatic Activity Index (IMHAI), as well
      as to compare inflammatory scores and stages in the groups created according to
      the number of portal area (PA). MATERIALS AND METHODS: The study included 107
      patients that underwent liver biopsy in 2011 being diagnosed with chronic viral
      hepatitis. Age, gender and type of viral hepatitis were retrospectively reviewed
      and histological findings such as IMHAI inflammatory score and stage,
      hepatosteatosis and ground glass hepatocytes were re-assessed by two
      pathologists. RESULTS: Of the present cases, 97 had chronic hepatitis B, 5 had
      chronic hepatitis C, and 5 had chronic hepatitis BDThe group with PA number of 2
      4 consisted of 8 cases and the group with PA number of 11 and over consisted of
      37 cases. CONCLUSION: Statistical analysis performed by comparing IMHAI
      inflammatory score and stage with PA revealed that score and stage were
      significantly higher in PA >= 11 groups as compared to PA 2-4 group.

PMID- 24326810
TI  - Reducing maternal deaths in a low resource setting in Nigeria.
AB  - OBJECTIVE: To assess the impact of the adoption of evidence based guidelines on
      maternal mortality reduction at Enugu State University Teaching Hospital,
      Nigeria. MATERIALS AND METHODS: A retrospective review of all maternal deaths
      between 1 st January, 2005 and 31 st December, 2010 was carried out. Evidence
      based management guidelines for eclampsia and post-partum hemorrhage were
      adopted. These interventions strategy were carried out from 1 st January, 2008-31
      st December, 2010 and the result compared with that before the interventions
      (2005-2007). MAIN OUTCOME MEASURE: Maternal mortality ratio (MMR) and case
      fatality rates. RESULTS: There were 9150 live births and 59 maternal deaths
      during the study period, giving an MMR of 645/100 000 live births. Pregnant women
      who had no antenatal care had almost 10 times higher MMR. There was 43.5%
      reduction in the MMR with the interventions (488 vs. 864/100 000 live births P =
      0.039, odds ratio = 1.77). There was also significant reduction in case fatality
      rate for both eclampsia (15.8% vs. 2.7%; P = 0.024, odds ratio = 5.84 and Post
      partum hemorrhage (PPH) (13.6% vs. 2.5% P value = 0.023, odds ratio = 5.5.
      Obstetric hemorrhage was the most common cause of death (23.73%), followed by the
      eclampsia. CONCLUSION: Administration of evidence based intervention is possible
      in low resource settings and could contribute to a significant reduction in the
      maternal deaths.

PMID- 24326811
TI  - Comparative evaluation of root canal disinfection by conventional method and
      laser: an in vivo study.
AB  - OBJECTIVE: The aim of this study was to comparatively evaluate in vivo the
      disinfecting ability of conventional method and lasers in root canals. MATERIALS
      AND METHODS: Study criteria included 60 single rooted teeth, which were indicated
      for root canal therapy followed to dental caries and trauma with intact crowns.
      Such selected patients were randomly divided into 2 groups, namely, Group A (30
      teeth) and Group B (30 teeth). All clinical procedures were carried out under
      strict aseptic precautions. The teeth in Group A were subjected to biomechanical
      preparation followed by the treatment with the help of diode laser containing the
      gallium aluminum and arsenic, which emitted 980 nm wavelengths. The teeth in
      Group B were treated with routine method of biomechanical preparation along with
      irrigation using sodium hypochlorite and hydrogen peroxide. The microbiological
      samples were taken immediately after the access preparation and after the
      completion of the root canal disinfection and were sent for microbiological
      analysis. RESULTS: The teeth in Group A showed presence of common strains of
      bacteria ranging from Streptococci, Staphylococci, Klebsiella, and Pseudomonas.
      Reduction in the growth of microorganisms was found for all types of
      microorganisms. Only 8 samples exhibited the growth after treatment with laser.
      Results of Group B also showed the presence of common strains of anaerobic and
      aerobic bacteria as shown in earlier studies, predominantly Staphylococcus,
      Streptococci, and Pseudomonas. Statistical analysis showed non-significant P
      values for the microorganisms; however, only 3 samples showed the growth after
      treatment with conventional technique using sodium hypochlorite and hydrogen
      peroxide. CONCLUSION: Conventional method by using sodium hypochlorite and
      hydrogen peroxide as irrigating solutions is highly effective in disinfecting the
      root canal. Lasers when used can also reduce the bacterial load of the infected
      root canal.

PMID- 24326812
TI  - Effects of the topical hemostatic agent Ankaferd Blood Stopper on the incidence
      of alveolar osteitis after surgical removal of an impacted mandibular third
      molar.
AB  - BACKGROUND: Alveolar osteitis (AO) is a commonly seen post-operative complication
      during the wound-healing period after permanent tooth extraction or surgical
      removal of impacted third molar teeth. OBJECTIVES: The aim of this clinical study
      was to evaluate the effects of administration of the topical hemostatic agent
      Ankaferd Blood Stopper (ABS) into the socket on AO formation after impacted
      mandibular third molar extraction. PATIENTS AND METHODS: Bilaterally, 100 half
      impacted mandibular third molars were extracted in 50 patients. Then, 1.0 mL ABS
      was administered to achieve hemostasis in one half of the sockets and as a
      control, the other half was irrigated with 1.0 mL physiological serum after
      surgery. RESULTS: There was no statistically significant difference in terms of
      AO formation ( P > 0.05) between the extraction sites. However, the postoperative
      pain in ABS administration sites was higher than in the other sites for the first
      2 days after surgery ( P < 0.05). CONCLUSIONS: The results showed that ABS
      administration did not increase the incidence of AO formation. Thus, ABS can be
      used safely for hemostasis after impacted mandibular third molar surgery.

PMID- 24326813
TI  - The effect of orthodontic extraoral appliances on depression and the anxiety
      levels of patients and parents.
AB  - BACKGROUND: Psychosocial consequences and post-operative anxiety in patients
      after fixed orthodontic treatment are important parameters that must be evaluated
      by clinicians not to effect patient and their parent's psychosocial mood
      negatively. OBJECTIVE: The aim of this study was to evaluate the changes in
      depression and anxiety levels of orthodontic patients and their parents before
      the extraoral appliance therapy, and at a 1-year follow-up. MATERIALS AND
      METHODS: Patients and one of their parents responded to a series of
      questionnaires and evaluation scales in order to assess depression and anxiety
      levels. Two groups of patients and their parents were surveyed; one group that
      had not yet embarked on the treatment and another that had commenced extra-oral
      appliance therapy 1 year prior to the study. RESULTS: The 1-year-treatment group
      scored significantly higher than the pre-treatment group on the depression scale
      and the trait-anxiety scale. State-trait anxiety inventory scores did not differ
      significantly between the groups. The parents of the 1-year-treatment group also
      scored significantly higher on the Beck depression inventory than those of the
      pre-treatment group. CONCLUSION: The results of this study emphasize the need for
      due consideration of psychological parameters before and during treatment with
      extra-oral appliances, particularly with regard to depression and anxiety.

PMID- 24326814
TI  - Avascular necrosis in sickle cell (homozygous S) patients: predictive clinical
      and laboratory indices.
AB  - BACKGROUND: Pathogenetic mechanism as well as laboratory and clinical correlates
      of osteonecrosis in sickle cell have not been fully investigated. The aim of this
      study is to investigate the predictive value of the steady state white cell and
      platelet count as well as the frequency of bone pain crisis per annum to detect
      sickle cell patients who will eventually develop avascular necrosis (AVN).
      PATIENTS AND METHODS: A 5 year retrospective analysis of 122 homozygous S (HbSS)
      patients, aged 6-49 years (mean age 24.7 +/- 7 years), out of which 16 patients
      (13.1%) had developed AVN within the years under review. RESULTS: The prevalence
      of AVN in sickle cell patients was determined to be 13.1 per 1000. The steady
      state white cell count, platelet count, frequency of bone pain crisis and
      hematocrit, was compared in patients that develop AVN and those who had not over
      the period. Only the steady state platelet count was found to differ
      significantly ( P = 0.011) between these two patient groups and to correlate
      positively (Pearson correlation coefficient = -0.251) with development of AVN.
      The hematocrit, white cell count, and frequency of bone pain crisis were found
      neither to differ significantly nor correlate with the development of AVN.
      CONCLUSION: In conclusion, patients with a raised steady state platelet count may
      have a higher tendency to develop AVN and may require closer orthopedic review
      and prophylactic intervention.

PMID- 24326815
TI  - Indications for tonsillectomy and adenoidectomy: our experience.
AB  - BACKGROUND: Infection and obstruction are the most common indications for
      performing tonsillectomy and adenoidectomy. In the past, infection was the main
      indication for these procedures; however, in the last few decades obstruction is
      said to be more prominent as an indication when compared to infection. OBJECTIVE:
      The objective of this study was to report our observations of indications for
      tonsillectomy and adenoidectomy. MATERIALS AND METHODS: This is a 2 year
      retrospective analysis of case records of patients aged 0-18 years who have had
      tonsillectomy, adenoidectomy and adenotonsillectomy performed in a tertiary
      hospital. STATISTICAL ANALYSIS USED: IBM SPSS (for windows, version 19) software
      was used to analyze this data. RESULTS: A total of 115 patient's records were
      reviewed. Moreover, 33.9% were children under 3 years, 60.0% were between 4 years
      and 10 years and 6.1% were between the ages of 11 years and 18 years. Obstruction
      accounted for a total of 68.7% while infection accounted for only 31.3% of the
      indication for these procedures. CONCLUSION: Obstruction as an indication is
      proportionally higher in younger children while infection is proportionally
      higher in older children.

PMID- 24326816
TI  - Asymptomatic bacteriuria among pregnant women with sickle cell trait in Enugu,
      South Eastern Nigeria.
AB  - CONTEXT: Asymptomatic bacteriuria (ASB) in pregnancy is a major risk factor for
      developing acute cystitis and pyelonephritis, especially, among women with sickle
      cell disease. This study compared the prevalence, pattern, and microbiological
      characteristics of ASB in pregnancy between sickle cell trait (HbAS) and normal
      hemoglobin AA (HbAA) genotype subjects. MATERIALS AND METHODS: Culture and
      sensitivity of mid-stream urine samples were collected from 300 HbAS women and
      300 matched HbAA control at the antenatal clinic of University of Nigeria
      Teaching Hospital Enugu, Nigeria from August 2010 to December 2011. Analysis was
      both descriptive and inferential at 95% confidence levels. RESULTS: Prevalence of
      ASB in HbAS and HbAA women were 32.7% (98/300) and 32% (96/300) respectively (odd
      ratio (OR) =1.03 [95% confidence interval (CI) 0.73, 1.45]). Escherichia coli was
      the most common organism isolated in both the HbAS group (56.1%, 55/98) and
      control group (61.4%, 59/96), (OR = 0.80 [95% CI 0.45, 1.42]). The antibiotics
      with the highest microbial sensitivity were ciprofloxacin 90.8% (89/98) and
      gentamicin 100% (98/98) for HbAS and HbAA women respectively. CONCLUSIONS: The
      prevalence of ASB in pregnant women with HbAS in Enugu, Nigeria was high and did
      not vary significantly from that of woman with HbAA. Therefore, pregnant women
      irrespective of their sickle cell status would benefit from routine screening for
      ASB.

PMID- 24326817
TI  - Health education alone and health education plus advance provision of emergency
      contraceptive pills on knowledge and attitudes among university female students
      in Enugu, Nigeria.
AB  - This was an intervention study to compare the effects of health education alone
      and health education plus advance provision of emergency contraception (EC) pills
      on the knowledge and attitudes to EC by female students of University of Nigeria
      in South-East Nigeria. MATERIALS AND METHODS: A structured questionnaire was used
      to collect data in February, 2009 from 290 female students of a tertiary
      educational institution (140 in the study group and 150 from the control group)
      who were selected by multistage sampling. Subsequently, health education was
      conducted among all the students. In addition, a pack containing 2 tablets of EC
      pills (Postinor) was given only to the students in the study group. Three months
      after this intervention, its effects were assessed through a survey using the
      same structured questionnaire employed in the baseline survey. RESULTS: knowledge
      of EC was significantly higher among the study group than the controls at post
      intervention, P < 0.05. Attitudes to EC were also more favorable at post
      intervention survey among the study group, P < 0.05 in most of the variables.
      CONCLUSION/RECOMMENDATION: Health education plus advance provision of EC pills
      effectively improved knowledge and attitudes to EC among female students of
      tertiary institutions more than health education alone and this should be
      promoted.

PMID- 24326818
TI  - Refractive errors in patients attending a private hospital in Jos, Nigeria.
AB  - OBJECTIVE: This study was carried out to determine the prevalence and pattern of
      refractive error in patients presenting to a private hospital. MATERIALS AND
      METHODS: Records of all patients who presented at the hospital from 2000 to 2009
      with visual acuity (VA) of 6/9 or less and showed improvement in distance vision
      of one or more lines with refraction were reviewed. The eye with the better
      presenting visual acuity was used for classifying the patient. The spherical
      equivalent refraction was used with the formula (sphere plus cylinder/2).
      RESULTS: Two thousand eight hundred ninety eight patients were seen at the
      hospital for various eye problems. Six hundred one (20.7%) patients with distant
      VA which improved with refraction were considered for this analysis. Two hundred
      twenty one (36.8%) of patients with refractive error were visually impaired (VA
      <6/12-3/60). Blindness (<3/60 - none perception of light) was seen in 91 (15.1%)
      of the patients, seven of whom were aphakic. Best corrected visual acuity
      increased the number of patients with normal visual acuity from 289 (48.1%) to
      579 (96.3%). Overall visual impairment (VI) (<6/12-3/60) was reduced from 221
      (36.8%) to 22 (3.6%). Severe visual impairment and blindness were completely
      eliminated just with refractive correction. Of those with refractive error, there
      were 35.8% with myopia, 29.5% with hypermetropia and 34.8% with astigmatism.
      Males had slightly more myopia and astigmatism, and female more hypermetropia
      though the difference was not statistically significant. Refractive error was
      seen more among the students 207 (34.4%) and civil servants 189 (31.4%) and least
      among the artisans 7 (1.2%). Anisometropia of <= 1 D, >1-2 D, >2-3 and > 3 D were
      found in 76.5%, 11.8%, 5% and 5.0% respectively. CONCLUSION: The study shows that
      refractive error is a common cause of VI and myopia is the most common type. It
      confirms that most of the refractive error can be corrected with off-the-shelf
      spectacles.

PMID- 24326819
TI  - Fatal scorpion sting in a child.
AB  - Fatal scorpion stings are rare in Nigeria. Hitherto, there has been no report
      from Nigeria of death following scorpion stings. This report is that of a 2-year
      old boy who was stung by a scorpion while playing outside his home environment in
      Osogbo, South West Nigeria. He subsequently presented to the Children Emergency
      Unit of Ladoke Akintola University of Technology Teaching Hospital, Osogbo, in
      pain and with features of shock. He died within 2 h of admission despite all
      treatment given to relieve pain and manage shock. The case is reported in order
      to share the important lessons learned. 

PMID- 24326820
TI  - Multiple bilateral submandibular gland sialolithiasis.
AB  - Sialolithiasis accounts for the most common etiology of salivary gland
      obstruction which leads to recurrent painful swelling of the involved gland which
      often exacerbates while eating. Stones may be encountered in any of the salivary
      glands but most frequently in the submandibular gland and its duct. Simultaneous
      sialolithiasis in more than one salivary gland is rare, occurring in fewer than
      3% of cases. Seventy to 80% of cases feature solitary stones; only about 5% of
      patients have three or more stones, the case report which we are presenting here
      had three submandibular sialoliths involving both the submandibular glands which
      were removed by intraoral approach and no post-operative complications were
      noted. 

PMID- 24326821
TI  - Rectal and genital prolapse in Nigerian newborns: case reports and review of the
      literature.
AB  - Genital prolapse in the newborn is a rare clinical condition often times seen in
      association with congenital myelo-meningocele, or this could occur following
      shigellosis infection. We therefore report two neonates with rectal prolapse
      following diarrhea and utero-vaginal prolapse associated with congenital spinal
      bifida. 

PMID- 24326822
TI  - Multiple organ dysfunction caused by parathyroid adenoma-induced primary
      hyperparathyroidism.
AB  - We present a 27-year-old male with multiple organ dysfunction caused by
      parathyroid adenoma-induced primary hyperparathyroidism (PHPT). Initially, the
      patient experienced a sudden onset of gastrointestinal symptoms, polyuria,
      polydipsia, bone pain, renal dysfunction, nephrolithiasis, and acute
      pancreatitis, symptoms associated with hypercalcemia. Biochemical findings
      suggested PHPT. Renal biopsy showed an acute tubular injury and massive calcium
      deposits in the tubular epithelial cells and tubular lumina. Moreover, neck
      ultrasonography suggested the possibility of a parathyroid tumor. We excised his
      right parathyroid gland. Histopathological analysis revealed features of a
      parathyroid adenoma. Post-operatively this patient had normal serum calcium
      concentration, but was renally insufficient. A recent repeat biopsy showed
      chronic renal tubular injury. Our findings illustrate the complications of
      various systems that can occur in patients with PHPT caused by a parathyroid
      adenoma. 

PMID- 24326823
TI  - Does immunohistochemistry affect response to therapy and survival of inoperable
      non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive
      cases.
AB  - Whether non-small cell lung carcinoma (NSCLC) unveiled by immunohistochemistry
      (IHC) has the same clinical outcome as those typed by morphology is still matter
      of debate. A total of 145 stage III-IV, consecutive inoperable NSCLC patients
      treated by chemotherapy (133 cases) or EGFR tyrosine kinase inhibitor (12 cases)
      and including 100 biopsies, 11 surgical specimens, and 34 cytological samples had
      originally accounted for 120 adenocarcinomas (ADs), 19 squamous cell carcinomas
      (SQCs), and 6 adenosquamous carcinomas (ADSQCs) by integrating morphology and
      thyroid transcription factor-1 (TTF1)/p40 IHC. Thirty-two NSCLC-not otherwise
      specified (NSCLC-NOS) cases were identified by morphology revision of the
      original diagnoses, which showed solid growth pattern (P < .001), 22 ADs, 5 SQCs,
      and 5 ADSQCs by IHC profiling (P < .001), and 10 gene-altered tumors (3 EGFR, 5
      KRAS, and 2 ALK). While no significant relationships were observed between
      response to therapy and original, morphology or IHC diagnoses, driver mutations
      and tumor differentiation by TTF1 expression, AD run better progression-free
      survival (PFS) or overall survival (OS) than other tumor types by morphology (P =
      .010 and P = .047) and IHC (P = .033 and P = .046), respectively. Furthermore,
      patients with NSCLC-NOS confirmed as AD by IHC tended to have poorer OS (P =
      .179) and PFS (P = .193) similar to that of ADSQC and SQC (P = .702 and P = .540,
      respectively). A category of less differentiated AD with poorer prognosis on
      therapy could be identified by IHC, while there were no differences for SQC or
      ADSQC. The terminology of "NSCLC-NOS, favor by IHC" is appropriate to alert
      clinicians toward more aggressive tumors. 

PMID- 24326824
TI  - Primary intraosseous schwannoma in tibial epiphysis with unique
      immunohistochemical phenotype: a case report.
AB  - Schwannoma is a benign peripheral nerve sheath neoplasm of soft tissue that
      consistently demonstrates immunohistochemical staining for S100 protein.
      Intraosseous location of schwannoma is very uncommon. We report the first case of
      an intraosseous schwannoma located in the epiphysis of tibia in an adult patient.
      Radiologically, it mimicked a primary bone tumor and despite benign histological
      appearance, the tumor eroded cortical bone. Morphologically on routine stains and
      electron microscopy it has features of a schwannoma. But by immunohistochemistry,
      the tumor was positive for both desmin and S100 protein in the same region. 

PMID- 24326825
TI  - Clinicopathologic parameters related to recurrence and locoregional metastasis in
      180 oral squamous cell carcinomas.
AB  - Lymph node metastasis (LNm), local recurrence (LR), and second primary tumor
      (SPT) after primary surgery for oral squamous cell carcinoma (OSCC) have been
      considered poor prognostic entities in terms of survival rate. The purpose of
      this study was to identify the clinicopathologic parameters significantly related
      to LNm, LR, and SPT. Records from 180 patients who underwent radical surgery for
      OSCC were retrospectively reviewed. Perineural invasion was significantly related
      to LNm (18% vs 8%) and LR (15% vs 5%), while the status of the surgical margin
      (10% in case of clear margins, 18% close margins, and 24% involved margins),
      namely epithelial precursor lesions (43%) was an independent factor influencing
      SPT. Perineural invasion proved a good prognostic factor for early events, either
      LNm or LR, while a surgical margin width less than 5 mm or with epithelial
      precursor lesions may be considered a risk factor for late events such as SPT.

PMID- 24326826
TI  - A Clinicopathologic Analysis of 207 Cases of Benign Fibro-Osseous Lesions of the
      Jaws.
AB  - Benign fibro-osseous lesion (BFOL) is a distinct group of jaw entities composed
      of fibrocellular tissue and mineralized materials. In this study, we examined the
      epidemiological, clinical, and pathological features of patients with BFOL.
      Records and microslides of 207 BFOLs submitted to pathology service were
      retrospectively reviewed. Overall, fibrous dysplasia (FD) was the most prevalent
      (36.7%), followed by ossifying fibroma (OF; 32.4%), osseous dysplasia (OD;
      24.6%), and juvenile ossifying fibroma (JOF; 6.3%). Female predilection was
      noted. FD and JOF were common in maxilla, whereas most OF and OD affected the
      mandible. Most patients with FD and OF presented with painless swelling, while
      patients with OD were symptomless. The majority of FD specimens showed woven
      bone, while a mixture of woven bone and cementum-like materials was often noted
      in OF and OD. Our data show variations in the clinicopathologic features of
      BFOLs. A thorough examination of all aspects of BFOL patients is imperative for
      accurate diagnosis. 

PMID- 24326827
TI  - Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between
      nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.
AB  - Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin
      lymphoma (NLPHL) are considered separate entities with different prognosis and
      treatment. However, morphologic features can be similar and immunohistochemical
      studies are essential in the distinction; thus, determination of additional
      biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an
      interacting partner co-expressed with BCL6 in germinal centers and highly
      expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely,
      loss of the LRF gene in mouse hematopoietic stem cells results in complete block
      of early B cell development with concomitant Notch de-repression, indicating its
      critical role in B versus T cell fate decision at the hematopoietic stem cell
      stage. For the first time, we show that LRF/Pokemon is predominantly expressed in
      NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while
      Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon
      expression with higher NOTCH1 expression. We illustrate a potential functional
      interaction between LRF and BCL6 in NLPHL pathogenesis, and differential
      expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential
      expression, making for an additional diagnostic marker and therapeutic target. 

PMID- 24326828
TI  - Mucinous carcinoma of the rectum: a distinct clinicopathological entity.
AB  - PURPOSE: The definition of mucinous tumours relies on quantification of the
      amount of mucus produced by neoplastic cells within the rectum. This has changed
      over the years to include varying degrees of mucin production. The inconsistency
      of diagnosis has led to conflicting reports in the literature regarding clinical
      outcomes and treatment response. A universally accepted definition and improved
      imaging and surgical techniques in the last decade are now challenging the
      traditional view of these tumours. The aim of this review was to present the
      current evidence on the clinicopathological characteristics of mucinous tumours
      of the rectum. METHODS: A systematic review was conducted using Preferred
      Reporting for Systematic Reviews and Meta-Analyses guidelines. A literature
      search was performed using the Ovid SP to search both EMBASE and MEDLINE
      databases, Google Scholar and PubMed to find all studies relating to mucinous
      carcinoma of the rectum. The search dates were between 1 January 1965 and 1 March
      2013. RESULTS: Mucinous tumours comprise 5-20 % of all rectal cancers and
      commonly present at a more advanced stage and in younger patients. They are
      readily identified on MRI, and the diagnosis is confirmed on histological
      analysis, demonstrating more than 50 % of extracellular mucin within the tumour
      complex. They carry an overall worse prognosis compared to adenocarcinoma of the
      same stage. The response to oncological treatment remains controversial.
      CONCLUSION: Mucinous tumours of the rectum are less well understood than non
      mucinous adenocarcinoma. This is due to the inconsistent histopathological
      definitions of the past making comparison of clinical outcome data difficult.
      They remain challenging to treat and are associated with a poor prognosis. A
      universally accepted definition and the role of imaging techniques such as MRI to
      accurately detect mucinous tumours are likely to lead to a better understanding
      of these cancers.

PMID- 24326829
TI  - Hemospray application in nonvariceal upper gastrointestinal bleeding: results of
      the Survey to Evaluate the Application of Hemospray in the Luminal Tract.
AB  - BACKGROUND: Hemospray TM (TC-325) is a novel hemostatic agent licensed for use in
      nonvariceal upper gastrointestinal bleeding (NVUGIB) in Europe. GOALS: We present
      the operating characteristics and performance of TC-325 in the largest registry
      to date of patients presenting with NVUGIB in everyday clinical practice.
      METHODS: Prospective anonymized data of device performance and clinical outcomes
      were collected from 10 European centers using the multicentre SEAL survey (Survey
      to Evaluate the Application of Hemospray in the Luminal tract). TC-325 was used
      as a monotherapy or as second-line therapy in combination with other hemostatic
      modalities at the endoscopists' discretion. RESULTS: Sixty-three patients (44
      men, 19 women), median age 69 (range, 21 to 98) years with NVUGIB requiring
      endoscopic hemostasis were treated with TC-325. There were 30 patients with
      bleeding ulcers and 33 with other NVUGIB pathology. Fifty-five (87%) were treated
      with TC-325 as monotherapy; 47 [85%; 95% confidence interval (CI), 76%-94%] of
      them achieved primary hemostasis, and rebleeding rate at 7 days was 15% (95% CI,
      5%-25%). Primary hemostasis rate for TC-325 in patients with ulcer bleeds was 76%
      (95% CI, 59%-93%). Eight patients, who otherwise may have required either surgery
      or interventional radiology, were treated with TC-325 as second-line therapy
      after failure of other endoscopic treatments, all of whom achieved hemostasis
      following the adjunct of TC-325. CONCLUSIONS: This multicentre registry
      identifies potentially useful characteristics of Hemospray (TC-325) when used
      either as monotherapy or as a rescue therapy in a wide variety of ulcer and
      nonulcer NVUGIB.

PMID- 24326830
TI  - Lung cancer survival and deletion of GSTM1 and GSTT1 genes. A case-series from
      Spain.
AB  - AIMS AND BACKGROUND: Lung cancer has a high incidence, and only 15% of all cases
      are alive 5 years after the diagnosis. Identifying the role of the genes
      implicated in the success of chemotherapy agents is crucial to predict survival.
      The objective of the study was to assess the effect of GSTM1 and GSTT1 gene
      deletion on lung cancer survival. METHODS AND STUDY DESIGN: A consecutive
      sampling of lung cancer cases was performed in 1999-2000 at the University
      Hospital of Santiago de Compostela, Spain, and GSTM1 and GSTT1 genes were
      genotyped. The effect of GSTM1 and GSTT1 deletion on survival was analyzed with
      the logrank test and with Cox regression. RESULTS: A total of 132 individuals
      were included, and more than half of them had stage IV lung cancer at diagnosis.
      Survival was similar irrespective of the presence or absence of the GSTM1 gene,
      whereas those with deleted GSTT1 had a significantly shorter survival. In
      multivariate Cox regression analysis, no significant effect was observed for the
      deletion of any of the genes, although there was a tendency towards a worse
      survival for those with deletion of GSTT1. The main limitation was that stage at
      diagnosis could not be considered in the analysis since most of the patients were
      diagnosed at stage IV. CONCLUSIONS: GSTT1 appears to influence lung cancer
      survival whereas GSTM1 seems to have no effect.

PMID- 24326831
TI  - Abortion and breast cancer: case-control study.
AB  - AIMS AND BACKGROUND: The aim of the present study was to examine if certain
      aspects of a woman's experience of abortion might be associated with the risk of
      breast cancer. METHODS AND STUDY DESIGN: The case-control study was conducted in
      Kragujevac (Serbia) during the period 2004-2005. The case group (191 women)
      consisted of patients with newly diagnosed first primary breast cancer, which was
      histologically confirmed. The control group (191 women), individually matched by
      age (+/- 2 years), hospital admittance and place of residence (rural/urban) to
      the respective cases, was selected from female patients admitted for other
      diseases. The analysis was restricted to parous women (168 cases and 171
      controls). RESULTS: Breast cancer risk was reduced among women who had a history
      of any abortion (adjusted OR, 0.46; 95% CI, 0.24-0.88). The protective effect was
      found for both induced abortion (adjusted OR, 0.47; 95% CI, 0.25-0.90) and
      spontaneous abortion (adjusted OR, 0.31; 95% CI, 0.10-0.98). It seems that these
      associations did not depend on the number of abortions, age at first abortion, or
      gestational age at first aborted pregnancy. CONCLUSIONS: Our study suggests that
      even short pregnancies ending in abortion add to the protection against breast
      cancer.

PMID- 24326832
TI  - Risk factors for well-differentiated thyroid cancer in men.
AB  - AIMS AND BACKGROUND: Thyroid cancers are relatively rare tumors that appear more
      frequently in women than in men. Accordingly, most studies focus on studying risk
      factors for thyroid cancer in women and consequently on various hormonal or
      reproductive factors that are specific for women. The aim of our study was to
      examine risk factors for developing well-differentiated thyroid cancer in men.
      Heretofore, we did not encounter in the literature a study that was solely
      focused on studying risk factors for well-differentiated thyroid cancer in men.
      METHODS: A case-control study was performed from 2005 to 2010. The case group
      included 204 consecutive well-differentiated thyroid cancers in male patients
      (180 papillary and 24 follicular including Hurthle cell). The control group
      comprised the same number of cases. Patients were individually matched by gender,
      age and place of residence. Statistical analysis included conditional univariate
      and multivariate logistic regression methods. RESULTS: According to univariate
      logistic regression, well-differentiated thyroid cancer in men was significantly
      related to smoking status, duration of smoking, number of cigarettes smoked per
      day, history of goiter or thyroid nodules, history of non-thyroid cancer,
      diabetes mellitus, radiotherapy of the head and neck, and history of malignant
      tumors. According to multivariate logistic regression, it was independently
      related to smoking status (OR = 0.36; 95% CI, 0.19-0.69), history of goiter or
      thyroid nodules (OR = 9.19; 95% CI, 1.25-64.58), and a history of malignant
      tumors (OR = 2.11; 95% CI, 1.19-7.33). CONCLUSIONS: Risk factors for well
      differentiated thyroid cancer in men were goiter or thyroid nodules and family
      history of malignant tumors. Cigarette smoking was negatively associated with the
      disease.

PMID- 24326833
TI  - Biweekly triplet chemotherapy with gemcitabine, cisplatin and vinorelbine for
      advanced chemotherapy naive non-small cell lung cancer.
AB  - AIMS AND BACKGROUND: To investigate the efficacy and tolerability of biweekly
      scheduled triplet chemotherapy consisting of gemcitabine, cisplatin and
      vinorelbine for chemotherapy-naive advanced non-small cell lung cancer. METHODS
      AND STUDY DESIGN: Patients with stage IIIB/IV non-small cell lung cancer and
      performance status of 0-2 were eligible. Patients who had brain metastasis and of
      an older age were also enrolled in the study. The triplet combination
      chemotherapy consisted of gemcitabine, cisplatin and vinorelbine at the doses of
      1000 mg/m(2), 25 mg/m(2) and 50 mg/m(2), respectively, were administered on day 1
      and 14, every 28 days, up to 6 cycles. RESULTS: Thirty patients were enrolled in
      the study. Median age was 60 years (range, 42-74). Most of the patients (83%) had
      metastatic disease and 7 patients (23%) had brain metastasis. In assessing 24
      patients for response evaluation, none had complete response. Partial responses
      were achieved in 18 (60%) patients. Four patients (13%) had stable disease and 2
      (7%) progressed. Thirteen percent and 20% of the patients developed severe (grade
      3-4) neutropenia and anemia, respectively. Febrile neutropenia, severe
      thrombocytopenia, hepatic and renal toxicity were not seen. Overall and
      progression-free survival were 8.15 and 7.15 months, respectively. Patients who
      had no brain metastasis ( P = 0.069), who had more than 3 courses of chemotherapy
      (P <0.001), and who had chemotherapy applied without dose reduction (P = 0.018)
      had better survivals. CONCLUSIONS: The biweekly schedule of the triplet
      chemotherapy combination including gemcitabine, cisplatin and vinorelbine was
      effective in advanced, mostly metastatic non-small cell lung cancer with
      acceptable and manageable side effects.

PMID- 24326834
TI  - Efficacy and safety of concurrent chemoradiotherapy with cisplatin and docetaxel
      in patients with locally advanced nasopharyngeal cancers.
AB  - AIMS AND BACKGROUND: Chemoradiation using cisplatin-based regimens has become the
      standard care in the treatment of nasopharyngeal cancers. The impact of taxanes
      as radiosensitizing agents with concurrent chemoradiation regimens is unknown. We
      retrospectively evaluated the efficacy and tolerability of weekly cisplatin +
      docetaxel combination with chemoradiation in locally advanced nasopharyngeal
      cancers. METHODS: Forty-two patients with locally advanced nasopharyngeal cancers
      (59.5% stage IV, 23.3% stage III, and 16.7% stage II) were assessed
      retrospectively. Total radiation dose to the planning target volume of gross
      disease (primary and/or node) was 70 Gy/35 fractions, 5 fractions per week.
      Minimum doses of 60 Gy and 50 Gy were administered to planning target volume of
      elective high-risk and low-risk disease, respectively. Chemotherapy consisted of
      weekly cisplatin (20 mg/m(2)) + docetaxel (20 mg/m(2)) concurrently with
      radiotherapy. RESULTS: The median age of the patients was 46.5 years (range, 17
      79). Objective response rate was 86%. The 4-year progression-free survival and
      overall survival were 65.4% and 91.3%, respectively. The most common grade 3 and
      4 toxicities were mucositis (48%), nausea (22%), neutropenia (12%), dermatitis
      (5%), fatigue (5%) and weight loss (5%). CONCLUSIONS: Weekly cisplatin and
      docetaxel concurrent with radiotherapy for locally advanced nasopharyngeal
      cancers was found tolerable with a high efficacy.

PMID- 24326835
TI  - Hypofractionated intensity-modulated simultaneous integrated boost and image
      guided radiotherapy in the treatment of high-risk prostate cancer patients: a
      preliminary report on acute toxicity.
AB  - AIMS AND BACKGROUND: To evaluate acute toxicity of hypofractionated intensity
      modulated radiotherapy with simultaneous integrated boost and image-guided
      radiotherapy in the treatment of high-risk prostate cancer patients. METHODS:
      Between November 2009 and March 2012, 59 patients with high-risk prostate cancer
      were enrolled. The eclipse inverse planning system (Varian) was used to calculate
      an IMRT plan with simultaneous integrated boost, delivering 68.75 Gy (2.75 Gy per
      fraction) to the prostate, 55 Gy (2.2 Gy per fraction) to the seminal vesicles
      and positive nodes, and 45 Gy (1.8 Gy per fraction) to the pelvis, 4 fractions
      per week, 25 fractions. Prior to each treatment, patients underwent a kilo
      voltage cone-beam CT performing an image-guided radiation therapy (IGRT). All
      patients were submitted to neoadjuvant, concomitant and adjuvant hormone therapy.
      RESULTS: The median follow-up for all patients was 13 months (range, 3-28). At
      the last follow-up, no grade 3 or 4 side effect was observed. Toxicity occurred
      as follows during the treatment: grade 1 and 2 gastrointestinal toxicity 5.2% and
      6.9%, respectively; grade 1 and 2 genitourinary toxicity 24.1% and 1.7%,
      respectively. Only 1.7% of the patients developed grade 3 genitourinary toxicity.
      No grade 3 gastrointestinal toxicity was observed. CONCLUSIONS: The present study
      demonstrated that 4/w hypofractionated intensity-modulated radiotherapy with
      simultaneous integrated boost and image-guided radiotherapy in patients with high
      risk prostate cancer is feasible and safe. Low acute toxicity rates were
      verified. Longer follow-up is needed to evaluate the outcomes in terms of late
      toxicity and survival.

PMID- 24326836
TI  - Hypofractionated intensity-modulated radiotherapy using simultaneous integrated
      boost technique with concurrent and adjuvant temozolomide for glioblastoma.
AB  - AIMS AND BACKGROUND: We assessed the therapeutic efficacy of combined
      hypofractionated intensity-modulated radiotherapy with temozolomide in patients
      with primary glioblastoma. METHODS AND STUDY DESIGN: Thirty-nine patients with
      histologically confirmed glioblastoma were accrued. Using the simultaneous
      integrated boost technique, a dose of 50 Gy in 5-Gy fractions was applied to the
      gross tumor volume, together with 40 Gy in 4-Gy fractions and 30 Gy in 3-Gy
      fractions to the 1- and 2-cm margins from the gross tumor volume, respectively.
      Patients were also treated with concurrent temozolomide during intensity
      modulated radiotherapy, followed by six cycles of adjuvant temozolomide. RESULTS:
      Median follow-up was 16.8 months (range, 4.3-54.3). Tumor progression was
      observed in 28 patients (71.8%), and the median time to progression was 6.8
      months. Median survival was 16.8 months, and it was affected significantly by the
      extent of surgery. During adjuvant temozolomide treatment, 3 patients (9.7%)
      developed grade 3-4 hematologic or hepatic toxicity. Radiation necrosis developed
      in 7 patients (17.9%) and massive necrosis, requiring emergency surgery, in 1
      patient (2.6%). CONCLUSIONS: The regimen of hypofractionated intensity-modulated
      radiotherapy with temozolomide showed a relatively good outcome in patients with
      glioblastoma. Further studies are required to define the optimal fraction size
      for glioblastoma using this highly sophisticated radiation technique.

PMID- 24326837
TI  - Palliative two-dimensional radiotherapy of pancreatic carcinoma: a feasibility
      study.
AB  - AIMS AND BACKGROUND: The aim of the study was to analyze the dose to be
      administered with two-dimensional involved-field palliative radiotherapy in
      advanced pancreatic carcinoma with respect to current dose-volume constraints
      (QUANTEC). METHODS AND STUDY DESIGN: The following standard regimens were
      evaluated: 30 Gy at 3 Gy/fraction (regimen A), 36 Gy at 2.4 Gy/fraction (regimen
      B), 45 Gy at 1.8 Gy/fraction (regimen C), and 50 Gy at 2 Gy /fraction (regimen
      D). The following constraints were considered: spinal cord Dmax <50 Gy, duodenum
      Dmax <55 Gy, liver Dmean <30 Gy, kidneys Dmean <15 Gy. For dose/fraction
      different from 1.8-2 Gy, the correction of constraints using a value of
      alpha/beta = 3 for late effects was considered. The calculation of dose/volume
      constraints was repeated for three different radiation beams: cobalt unit, 6 MV
      photons, and 15 MV photons. Standard field sizes were used and adapted according
      to the different beam types, using the parameters of our previous study. Respect
      of dose-volume constraints was assessed for each type of beam and treatment (dose
      per fractionation) in all patients. Treatments were considered acceptable in case
      of: 1) respect of the constraints for spinal cord and duodenum in all patients;
      2) respect in >10/15 patients of constraints for kidneys and liver. Therefore,
      minor violations (<10%) of the constraints for these organs were accepted (in
      less than 5/15 patients), in consideration of the palliative aim of treatment.
      RESULTS: In regimen A (30 Gy, 3 Gy/fraction), evaluated constraints were
      respected in all patients, regardless of the type of energy. In regimen B (36 Gy,
      2.4 Gy/fraction), constraints were met in all patients undergoing irradiation
      with 6 and 15 MV photons. However, using the cobalt unit, kidney constraint was
      respected only in 5 of 15 patients. In regimens C and D (45 Gy, 1.8 Gy/fraction
      and 50 Gy, 2 Gy/fraction, respectively), the constraint for the kidney was
      respected only in 2-5 patients, depending on the energy used. Furthermore, using
      50 Gy, the spinal cord constraint was not respected in 2-3 patients, depending on
      the beam used. Therefore, only the following treatments were considered
      acceptable: 1) 30 Gy, 3 Gy/fraction, regardless of the energy used; 2) 36 Gy, 2.4
      Gy/fraction, only for treatments performed with linear accelerator (6-15 MV).
      CONCLUSIONS: The clinical benefits of radiotherapy in pancreatic tumors should
      not be withheld from patients treated in centers only with two-dimensional
      technology. Prospective trials, particularly in developing countries, would be
      useful to evaluate the efficacy in this setting of involved-field two-dimensional
      treatments using the dose and fractionation defined in this analysis.

PMID- 24326838
TI  - Reconstructive head and neck surgery: oncological and functional results.
AB  - AIMS: The aim of this retrospective study is to review the experience in
      performing head and neck reconstruction surgery between 1989 and 2009 at the ENT
      Department of the University Hospital of Ferrara, Italy, considering the
      oncological as well as the functional and psychological outcome. METHODS AND
      STUDY DESIGN: Thirty-three consecutive patients were enrolled. Patients underwent
      flap reconstruction following primary or salvage surgery for squamous cell
      carcinoma of the oral cavity or oropharynx. Oncological results in terms of
      survival rate and disease-free interval, as well as functional and psychological
      results were evaluated. RESULTS: The oncological results, i.e. survival rate
      related to cancer stage and disease-free interval, were in agreement with those
      of the literature. Functional assessment, swallowing function and speech
      intelligibility were statistically poorer in patients affected by oropharyngeal
      malignancies than in patients affected by oral cancer. Quality of life was
      compromised in terms of reduced relationships and onset of depression or
      irritability. CONCLUSIONS: Reconstructive surgery can be considered a relatively
      standard procedure in the treatment of head and neck cancer. The main drawback is
      still related to the major impact on patients' quality of life and functional
      status.

PMID- 24326839
TI  - Thoracoscopic lobectomy: comparison of intraoperative and postoperative outcomes
      between 3 and 4 incision accesses.
AB  - AIMS AND BACKGROUND: Several techniques have been proposed to perform a video
      assisted thoracic lobectomy. We compared the results of a 3 versus 4-port
      procedure, analyzing intraoperative data, morbidity, and mortality. METHODS:
      Prospective analysis of 30 consecutive patients who underwent a 4-port approach
      video-assisted thoracic lobectomy (group A) and comparison with a historical
      series with 30 patients who had a 3-port video-assisted thoracic lobectomy (group
      B). RESULTS: The groups were comparable for clinical characteristics and
      pathological staging. There was no difference in operating time: median, 128 min
      for group A versus 129 min for group B (P = 0.9). There was a significant
      difference in rate of conversion to thoracotomy: 1 of 30 (3.3%) in group A and 7
      of 30 (23.3%) in group B (3 ports) (P = 0.02). In group A, 11 patients (36.7%)
      experienced postoperative complications and in group B, 13 patients (43.3%; P =
      0.6). The difference in median time to drain removal and median length of
      hospital stay between the two groups was not significant. There was a significant
      difference in persistent pain between group A and group B: 6 patients (20%) in
      group B presented with persistent neuropathic pain on regular medication (P =
      0.02). CONCLUSIONS: Our study showed that the 4-port approach was similar in
      operative time, length of drain and hospital stay but showed a statistically
      significant lower conversion rate and lower rate of persistent pain than the 3
      port access.

PMID- 24326840
TI  - Gastric remnant cancer patients had a better prognosis than upper-third gastric
      cancer patients in a case-control study after surgical treatment.
AB  - BACKGROUND: The aim was to compare the clinicopathological features and
      prognostic outcomes of gastric remnant carcinoma patients with those of patients
      with upper-third gastric cancer. METHODS: Clinical data extracted from 112
      gastric remnant carcinomas and 367 upper-third gastric cancer patients were
      analyzed to explore the clinicopathologic differences between two groups. After
      radical resection, prognostic difference between them was evaluated through a 1:2
      matched case-control study. RESULTS: The pattern of gastric remnant carcinomas
      showed a male predominance. Undifferentiated type histology, depth at T4 stage
      and distant metastases were more frequent in gastric remnant carcinomas than in
      upper-third gastric cancers (P <0.05). The radical resectability of gastric
      remnant carcinomas was lower and the multi-visceral resectabilitiy was relatively
      higher than the other group (P = 0.00). Gastric remnant carcinomas trended to
      have a higher incidence of metastases to either mesojejunum or lower mediastinal
      lymph nodes than upper-third gastric cancers, but patient survival was not
      significantly different. In the case-control study, gastric remnant carcinomas
      had a better prognosis than upper-third gastric cancers after radical resection
      when the clinicopathologic features and surgical treatment were matched.
      CONCLUSIONS: Although there was no significant prognostic distinction between
      gastric remnant carcinomas and upper-third gastric cancer, after radical surgical
      treatment, patients with the former had an even better prognosis.

PMID- 24326841
TI  - Prognostic role of neutrophil-to-lymphocyte ratio in advanced pancreatic ductal
      adenocarcinoma: impact of baseline fluctuation and changes during chemotherapy.
AB  - AIMS AND BACKGROUND: Inflammation has been implicated in carcinogenesis and
      progression of pancreatic cancer. The neutrophil-to-lymphocyte ratio is an index
      of systemic inflammation. We examined the prognostic role of the neutrophil-to
      lymphocyte ratio at baseline and the significance of intrapersonal variability of
      the ratio before and during chemotherapy. METHODS AND STUDY DESIGN: Advanced
      pancreatic adenocarcinoma patients who had received chemotherapy were included.
      Baseline clinical and biochemical parameters, including the neutrophil-to
      lymphocyte ratio, were extracted and analyzed. The neutrophil-to-lymphocyte ratio
      threshold was determined via recursive partitioning and assessed at diagnosis,
      prior to chemotherapy and during treatment. Overall survival was estimated via
      the Kaplan-Meier method and compared between groups with the logrank test.
      RESULTS: Between 2005 and 2011, 85 patients with locally advanced (n = 38) and
      metastatic disease were identified: 68% with a neutrophil-to-lymphocyte ratio >3
      had shorter median overall survival than patients with a neutrophil-to-lymphocyte
      ratio <3 (3.4 vs 9.4 months, P = 0.001). Pretreatment, 35% of repeat neutrophil
      to-lymphocyte ratios crossed the threshold of 3. A persistently elevated
      neutrophil-to-lymphocyte ratio >3 suggested a worse overall survival than in
      patients with a decreasing, increasing or persistently low neutrophil-to
      lymphocyte ratio (1.9 vs 8.2, 12.3 and 11.7 months, respectively, P <0.001).
      Twenty-three percent of patients had a >50% decrease in neutrophil-to-lymphocyte
      ratio following 4 weeks of chemotherapy, with a trend towards improvement in
      overall survival (12.5 vs 5.0 mo, P = 0.068). CONCLUSIONS: The baseline
      neutrophil-to-lymphocyte ratio is a validated marker for a poor prognosis.
      Multiple assessments of the pre-treatment neutrophil-to-lymphocyte ratio might be
      required. Reduction in the neutrophil-to-lymphocyte ratio during chemotherapy may
      be associated with improved survival.

PMID- 24326842
TI  - Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer.
AB  - BACKGROUND: The aim of the study was to assess the expression of the MMP-9 gene
      and -1562 C/T polymorphism in MMP-9 gene promoter in relation to
      clinicopathological parameters in predicting the clinical outcome of prostate
      cancer patients. METHODS: A total of 82 patients with histopathologically
      diagnosed prostate cancer were enrolled in the study. MMP-9 gene expression was
      assessed by reverse transcription-PCR method. MMP-9 (-1562 C/T) polymorphism
      variants were determined by the polymerase chain reaction-based restriction
      fragment length polymorphism method. RESULTS: MMP-9 expression and MMP-9 -1562
      polymorphism variants in relation to disease pathological stage (P = 0.006; P
      <0.0001, respectively), as well as to prognostic group (P = 0.019; P <0.0001,
      respectively), were statistically significant. Only MMP-9 -1562 polymorphism
      variants in relation to tumor differentiation grade (P = 0.044) were found to be
      statistically significant. Positive MMP-9 gene expression was associated with 5
      year survival rate of prostate cancer patients with pathological stage III (P =
      0.036) and for the patients in prognostic group III (P = 0.012). Patients with
      tumor differentiation grade G2 and with the identified CC variant had a
      significantly longer survival time than patients with the identified TT variant
      (P = 0.007). CONCLUSIONS: MMP-9 gene expression and MMP-9 -1562 polymorphism
      variants were associated with prostate cancer pathological stage and prognostic
      group. MMP-9 -1562 polymorphism CC variant was associated with prostate cancer
      tumor differentiation grade. Five-year survival analysis showed the relationship
      between MMP-9 gene expression and pathological stage III, as well as prognostic
      group III, whereas MMP-9 -1562 polymorphism variants, with tumor differentiation
      grade G2.

PMID- 24326843
TI  - Girdin correlated with autophagy in invasive ductal breast carcinomas.
AB  - AIMS AND BACKGROUND: Increasing evidence claims that autophagy is essential for
      breast cancer progression. Girdin was found highly expressed in breast cancers.
      It has been reported that Girdin attenuates autophagy in HeLa cells. We explored
      the relationship between Girdin expression and autophagic patterns in breast
      cancer. METHODS AND STUDY DESIGN: In the study, Girdin expression and autophagic
      activity were investigated in a series of 99 invasive ductal breast carcinomas
      after immunohistochemical staining for the autophagy-associated proteins LC3-II
      and Girdin. RESULTS: The level of Girdin expression negatively correlated with
      LC3-II level, which represents autophagic activity (r = -0.289), and positively
      correlated with lymph node metastasis (r = 0.472). Girdin level was found no
      different in the "diffuse cytoplasmic" and "stone-like" patterns of LC3-II.
      CONCLUSIONS: Up-regulated autophagy was negatively associated with Girdin level.
      There was a significant correlation between Girdin expression and lymph nodes
      metastasis in invasive ductal breast carcinoma.

PMID- 24326844
TI  - Clinical application of serum alpha-fetoprotein-IgM complexes on the diagnosis of
      primary hepatocellular carcinoma in Kazakh and Han populations.
AB  - AIMS AND BACKGROUND: We detected serum AFP-IgM levels in patients with primary
      hepatocellular carcinoma in Kazakh and Han populations to investigate the
      clinical significance of AFP-IgM in the diagnosis of hepatocellular carcinoma.
      METHODS AND STUDY DESIGN: Serum AFP-IgM levels were examined in 28 cases of
      hepatocellular carcinoma and 164 controls in the Kazakh population and in 85
      cases of hepatocellular carcinoma and 187 controls in the Han population. AFP-IgM
      was detected with the ELISA assay. RESULTS: In general, serum AFP-IgM levels of
      hepatocellular carcinoma patients in the Han population and hepatocellular
      carcinoma patients in the Kazakh population were statistically higher than those
      of controls, but there was no statistical significance between hepatocellular
      carcinoma patients in the Han and hepatocellular carcinoma patients in the Kazakh
      population. CONCLUSIONS: AFP-IgM is an encouraging serological marker and may be
      useful in the diagnosis of hepatocellular carcinoma.

PMID- 24326845
TI  - Assessment of chemokine serum levels in epithelial ovarian cancer patients.
AB  - AIMS AND BACKGROUND: The study was undertaken to investigate CCL2/MCP-1, CCL3/
      MIP-1alpha, CCL4/MIP-1beta, CCL5/RANTES and CXCL8/IL-8 women with epithelial
      ovarian cancer. METHODS AND STUDY DESIGN: Sixteen patients diagnosed with
      epithelial ovarian cancer and 18 healthy women with no evidence of malign
      neoplasia (control group) aged from 23 to 89 years (mean +/- SEM, 58.7 +/- 2.3)
      were included. The epithelial ovarian cancer patients underwent laparotomy and
      debulking surgery. Chemokines serum levels were measured by cytometric bead
      array. Statistical analysis was performed using Mann-Whitney and Kendall's tau. P
      <0.05 was considered statistically significant for all analyses. RESULTS: The
      tumor staging (FIGO) was classified into: I in 4 cases (25%), III in 5 cases
      (31.3%) and stage IV in 7 cases (43.8%). Sera chemokine dosages of CCL2/MCP-1 and
      CCL4/MIP-1beta were lower in epithelial ovarian cancer patients than in the
      control group (P = 0.021 and P = 0.030, respectively). No significant difference
      between groups was observed in the levels of CCL3/MIP-1alpha, CCL5/RANTES and
      CXCL8/IL-8. No association between the chemokines analyzed and tumor stage was
      found. The serum level of CCL4/MIP-1beta was correlated with CA-125. CONCLUSIONS:
      The study of serum levels of CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta,
      CCL5/RANTES and CXCL8/IL-8 chemokines in epithelial ovarian cancer patients
      identified a down-regulation in CCL2/MCP-1 and CCL4/MIP-1beta, which suggests
      that the two chemokines may play an important role in the pathophysiology of
      ovarian cancer.

PMID- 24326846
TI  - Increased expression of biological markers as potential therapeutic targets in
      Saudi women with triple-negative breast cancer.
AB  - AIMS AND BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive
      subtype of breast cancer that lacks the expression of hormone receptors and human
      epidermal growth factor receptor 2 (HER2). Although TNBC represents only 15% of
      all types of breast cancer, it accounts for a large number of metastatic cases
      and deaths. Because of the high metastatic rate and both local and systemic
      recurrence associated with TNBC, extensive research efforts are actively looking
      for target therapies to effectively treat this aggressive disease. Accordingly,
      this study has been initiated to investigate the differential expression of
      biological markers in TNBC and non-TNBC Saudi women that might be utilized as
      potential targeted therapy and/or predict the sensitivity to currently available
      therapeutic regimens. METHODS AND STUDY DESIGN: Two hundred formalin-fixed,
      paraffin-embedded (FFPE) breast cancer tissues were selected and divided into 3
      groups: benign breast tissues (20), TNBC tissues (80) and non-TNBC tissues (100).
      Expression of mRNA in FFPE tissues was analyzed using real-time polymerase chain
      reaction (RT-PCR) for the following genes: poly (ADP-ribose) polymerase 1 (PARP
      1), topoisomerase 2A (TOPO-2A), vascular endothelial growth factor (VEGF), C-MYC,
      basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP-2 and MMP
      9), human epidermal growth factor 1 (HER1) and multidrug resistance (MDR) genes.
      RESULTS: In the TNBC group, expression of PARP-1, TOPO-2A, HER1, C-MYC, VEGF,
      bFGF and MMP-2 showed a highly significant increase compared to the non-TNBC
      group. CONCLUSIONS: The results of this study suggest that (1) TNBC patients will
      benefit more from TOPO-2A inhibitors as well as antiangiogenic and antimetastatic
      therapies; (2) inhibition of these target genes is emerging as one of the most
      exciting and promising targeted therapeutic strategies to treat TNBC in which the
      intended targets are DNA repair, tumor angiogenesis and metastasis.

PMID- 24326847
TI  - Expression of cell metabolism-related genes in different molecular subtypes of
      triple-negative breast cancer.
AB  - AIMS AND BACKGROUND: We evaluated the difference in and significance of cancer
      cell metabolism by molecular subtyping of triple-negative breast carcinoma.
      METHODS: Tissue microarrays from 122 surgical specimens of triple-negative breast
      carcinoma patients and immunohistochemical staining for CK5/6, epidermal growth
      factor receptor, claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor,
      and gamma-glutamyltransferase 1 were used to classify triple-negative breast
      carcinoma as follows: basal-like type, molecular apocrine type, claudin low type,
      mixed type and null type. In addition, immunohistochemical staining for
      metabolism-related proteins such as c-myc, insulin-like growth factor (g)-1,
      hypoxia-inducible factor 1-1alpha, glucose transporter 1, carbonic anhydrase IX
      antibody, macrophage migration inhibitory factor, and pyruvate dehydrogenase
      kinase 1 was used to compare the differences according to molecular subtype and
      clinicopathological factors. RESULTS: The basal-like type showed the highest
      proportion of high glucose transporter 1 expression (P = 0.049) and carbonic
      anhydrase IX antibody expression (P = 0.008). Hypoxia-inducible factor 1-1alpha
      expression was associated with lymph node metastasis (P = 0.001) and central
      fibrotic zone (P = 0.012), and high glucose transporter 1 expression was related
      to high histologic grade (P = 0.007), cytokeratin 5/6 positivity (P = 0.002), and
      central fibrotic zone (P = 0.017). Finally, carbonic anhydrase IX antibody was
      associated with cytokeratin 5/6 positivity (P = 0.001) and central fibrotic zone
      (P = 0.048). CONCLUSIONS: Our study revealed the different characteristics of
      cancer cell metabolism according to the molecular subtypes of triple-negative
      breast carcinoma. Among them, basal-like type was the most glycolytic and acid
      resistant phenotype.

PMID- 24326848
TI  - Gastrointestinal carcinoids and colorectal cancers: is it a paracrine effect?
AB  - BACKGROUND: Carcinoid tumors are uncommon neuroendocrine tumors that account for
      less than 1% of gastrointestinal tract malignancies. They have a reported
      incidence of 1.3 per 100,000. Small bowel carcinoids are the commonest and have
      the highest incidence of associated second primary malignancies, followed by
      appendiceal and colorectal carcinoids. The most common second primary malignancy
      is colorectal adenocarcinoma. CASE SERIES: We report a series of 11 patients
      observed in the period 2006-2011 with primary gastrointestinal tract cancers and
      synchronous carcinoids discovered incidentally by the histopathologist in the
      resected primary cancer specimen. RESULTS: In all patients with synchronous
      carcinoids and colorectal adenocarcinoma there was a pattern of similar embryonic
      visceral origin. Is this a paracrine effect from biological peptides produced by
      the carcinoids?

PMID- 24326849
TI  - Recurrence due to neoplastic seeding in head and neck cancer: report of two cases
      and review of the literature.
AB  - AIMS AND BACKGROUND: Tumor progression due to seeding of tumor cells after
      definitive treatment for squamous cell carcinomas of the head and neck is an
      uncommon condition that can considerably worsen the outcome of patients with head
      and neck cancer. METHODS AND STUDY DESIGN: We report two cases of recurrence due
      to neoplastic seeding from oropharyngeal and oral cancer, respectively. We
      performed a literature review with MEDLINE as the main search engine. RESULTS:
      Seeding was found to occur most often in tracheotomy scars and gastrostomy sites.
      The oral cavity, hypopharynx and oropharynx were the primary sites in most cases,
      and advanced tumor stage seemed to be a risk factor for seeding. Treatment
      options include salvage surgery, which requires thorough resections, radiotherapy
      when possible, and palliative management. The prognosis of such events is poor.
      CONCLUSION: Although neoplastic seeding is a well-known phenomenon in cancer
      surgery, many questions remain unanswered, especially regarding preventive
      measures and management strategies.

PMID- 24326850
TI  - Well-differentiated neuroendocrine tumor of tailgut cyst. A rare entity with
      controversial medical opportunities.
AB  - The incidence of neuroendocrine tumors is rising, and this rise is explained by
      more than just better diagnostic procedures. About 85% of these neoplasms arise
      in gastrointestinal or pulmonary sites, but cases where the location is more
      unusual also occur in clinical practice. The tailgut cyst is a rare entity well
      described in the medical literature, but a neuroendocrine tumor within such a
      cyst is a very rare event, with about 30 cases described in the literature to
      date. In this report we present the case of a young woman with this unusual
      diagnosis. The characteristics of the case differ from most previous case reports
      in a few respects: the patient was a young rather than middle-aged female; she
      had a presacral mass with a significant solid component; at diagnosis, there was
      evidence of a lytic lesion in the coccyx. Despite this particular medical
      presentation, radical surgery was accomplished. In this disease the greatest risk
      is local relapse, but adjuvant radiotherapy may compromise the patient's
      fertility. We therefore opted for strict control only, but this decision might be
      debatable. 

PMID- 24326852
TI  - Nocardia yamanashiensis in an immunocompromised patient presenting as an
      indurated nodule on the dorsal hand.
AB  - BACKGROUND: Nocardia are ubiquitous, aerobic, gram-positive actinomycetes.
      Nocardiosis typically occurs in immunocompromised patients, although
      immunocompetent individuals can also be affected. PURPOSE: The purpose of this
      case study is to review the clinical characteristics and treatments of a unique
      form of cutaneous nocardiosis. MATERIALS AND METHODS: We retrospectively reviewed
      the medical literature using PubMed, searching the terms cutaneous, host,
      immunocompromised, Nocardia, primary, yamanashiensis. Patient reports and
      previous reviews of the subject were critically assessed and the salient features
      are presented. RESULTS: Cutaneous nocardiosis typically presents as pustular
      nodules and the lesions may progress to become abscesses, cellulitis, granulomas
      or keloid-like tumors. N. brasiliensis is the predominant species involved in
      primary cutaneous nocardiosis; other common Nocardia species involved in human
      disease are N. farcinica, N. abscessus, N. cyriacigeorgica, and N. nova. Only two
      individuals (including the patient presented here) with primary cutaneous
      infection by N. yamanashiensis have been described in the literature; a third
      clinical isolate was recovered from a lung biopsy. CONCLUSION: Nocardia
      yamanashiensis is a rare clinical form of primary cutaneous nocardiosis. 16S
      ribosomal gene sequencing, as well as Gram stain and modified Fite acid-fast
      stain, play a vital role in identifying this clinical variant.

PMID- 24326851
TI  - A case of NUT midline carcinoma with no HPV infection, slight EWSR1 rearrangement
      and strong expression of EGFR.
AB  - NUT midline carcinoma (NMC) is a rare neoplasm with a poor prognosis and
      involving mostly young patients. Here we describe a classic NMC with a BRD4-NUT
      fusion gene in a middle-aged woman. We also analyzed some biological features
      that could potentially influence its clinical behavior such as HPV infection,
      EWSR1 rearrangement, and the status of the EGFR gene. 

PMID- 24326853
TI  - Nontuberculous mycobacterial infection after therapy with temsirolimus for
      metastatic renal cell carcinoma.
AB  - We describe the case of a patient with metastatic renal cell carcinoma (mRCC) who
      developed a nontuberculous mycobacteria (NTM)-related pulmonary nodule during
      therapy with the mammalian target of rapamycin (mTOR) inhibitor temsirolimus.
      After discontinuation of temsirolimus treatment, a small pulmonary nodule with
      increased glucose uptake was detected on a positron emission tomography (PET)
      scan. A lung resection carried out to confirm and treat the suspected solitary
      metastasis of RCC yielded the surprising finding of a caseating granuloma
      containing NTM. A single PET-positive nodule presents a significant differential
      diagnostic dilemma in the setting of mRCC treated with mTOR inhibitors. Although
      the treatment of mRCC with temsirolimus can lead to immunosuppression and
      opportunistic infections, there is no report to our knowledge on the occurrence
      of NTM infections in mRCC patients treated with mTOR inhibitors. These infections
      should be included in the differential diagnosis of lung nodules. Interestingly,
      there is strong preclinical evidence pointing to direct and indirect
      antimycobacterial activity of mTOR inhibitors. We therefore hypothesize that
      while the seeding of NTM can occur during temsirolimus therapy due to T
      lymphocyte suppression, the infection may only become active after the
      discontinuation of mTOR inhibitor treatment. 

PMID- 24326854
TI  - Vanishing bile duct syndrome as a manifestation of Hodgkin's lymphoma: a case
      report and review of the literature.
AB  - Vanishing bile duct syndrome (VBDS) is characterized by cholestasis and
      progressive destruction of the intrahepatic bile ducts (ductopenia). The current
      definition of ductopenia is the loss of interlobular bile ducts in more than 50%
      of portal tracts. Ductopenia is believed, at a molecular level, to result from
      the misbalance in cell regeneration and apoptosis. In the literature various
      etiologies have been reported to cause ductopenia, with Hodgkin's lymphoma (HL)
      being listed as a rare example. How HL causes ductopenia remains ambiguous, and
      seems to be related to a paraneoplastic phenomenon causing cytokine release from
      lymphoma cells, not tumor infiltration or obstructive lymphadenopathy. VBDS is
      generally considered irreversible, unlike its histopathological counterpart,
      idiopathic cholestasis, where ductopenia is not present and liver function
      improves with therapy. Therefore, a distinction between the two is warranted.
      There have been only 19 case reports in the English literature associating VBDS
      with HL. Here we report a 64-year-old female patient who presented with
      distributive shock and jaundice. Initial laboratory values revealed leukocytosis,
      mild transaminase elevation with significantly elevated alkaline phosphatase,
      along with direct hyperbilirubinemia. During hospital stay, the patient's liver
      function progressively worsened. Further workup did not reveal ductal dilation or
      obstruction and there were unremarkable results for infectious and autoimmune
      etiologies. Imaging studies with biopsy revealed extensive lymphadenopathy
      consistent with HL; liver biopsy showed cholestasis and ductopenia. Despite
      chemotherapy the patient succumbed to progressive liver failure and sepsis. 

PMID- 24326855
TI  - Adenocarcinoma of the lung in Down syndrome: first clinical report.
AB  - Lung cancer is rare in persons with Down syndrome, and the clinical presentation
      of the disease has not been described in adults with intellectual disability. We
      report the first detailed clinical observation of a 33-year-old man with Down
      syndrome who developed an adenocarcinoma of the lung 30 years after an acute
      lymphoblastic leukemia in infancy. Despite advanced disease at initial
      presentation and extensive tumor spreading during the course of the disease, he
      presented with unusually mild symptoms. The scarcity of lung cancer in people
      with intellectual disability, and particularly those with Down syndrome, is due,
      in part, to reduced tobacco use. However, cytogenetic and molecular studies
      suggest that genes mapping to chromosome 21 may protect against lung cancer.
      Numerous reports also suggest that, in persons with Down syndrome and other
      intellectual disability, cancers are often discovered late, leading to loss of
      the chance of cure and recovery. 

PMID- 24326856
TI  - Chemotherapy with carboplatin and paclitaxel after failure of primary
      chemotherapy for advanced thymic carcinoma. A report of three cases and review of
      the literature.
AB  - For patients with inoperable thymic carcinoma, multidrug chemotherapy containing
      cisplatin and an anthracycline is often used as first-line chemotherapy. A
      commonly applied regimen is cisplatin + doxorubicin + vincristine +
      cyclophosphamide (ADOC). There are relatively few reports on the use of
      carboplatin and paclitaxel as first-line chemotherapy for thymic carcinoma. In
      addition, little is known about its efficacy as second-line chemotherapy in
      patients with advanced thymic carcinoma. We here report on three patients with
      thymic carcinoma who were treated with carboplatin and paclitaxel as second-line
      chemotherapy after failure of ADOC. According to the Response Evaluation Criteria
      in Solid Tumors version 1.1, one patient achieved a partial response and two
      patients achieved stable disease. The median progression-free survival was 6.7
      months and the median overall survival exceeded 3 years. Toxicities were well
      tolerated. Chemotherapy with carboplatin and paclitaxel appears to be effective
      as second-line chemotherapy for some persons with thymic carcinoma who fail ADOC.

PMID- 24326857
TI  - Solitary fibrous tumors of the pleura: a case report and review of the
      literature.
AB  - BACKGROUND: Solitary fibrous tumors of the pleura are rare and slow-growing
      neoplasms originating from the mesenchymal tissue underlying the mesothelial
      layer of the pleura. These tumors may have an unpredictable clinical course. Most
      cases occur in the sixth or seventh decades of life with no gender predilection,
      and more than 80% of cases are benign. The predominant clinical symptoms and
      signs are dyspnea, cough, chest pain, finger clubbing and hypoglycemia. However,
      because many patients are asymptomatic, the incidence rates are affected by the
      likelihood of its incidental detection, often through medical imaging of the
      chest. Surgical resection is the treatment of choice and is usually curative,
      even though local recurrence can occur many years after an adequate resection.
      METHODS: We reviewed the literature by performing a computerized search of
      MEDLINE, CANCERLIT and Embase with the terms fibrous tumor, pleura, surgery,
      immunohistochemical analysis. Articles and s were also identified by back
      referencing from other relevant papers. RESULTS: The clinical, radiological and
      pathological features of a 48-year-old woman with a primary solitary fibrous
      tumor of the pleura are reviewed and a literature search for other reported cases
      has been performed. CONCLUSIONS: Although localized fibrous tumors of the pleura
      are considered histologically benign, there is a risk of recurrence and malignant
      transformation. Complete surgical resection is mandatory and long-term clinical
      and radiological follow-up is indicated in all patients. For malignant cases
      complete surgical resection may not be adequate and studies are needed to define
      the role of preoperative and postoperative systemic treatment. Diagnosis is very
      difficult in limited samples such as fine-needle aspiration or needle-core tissue
      biopsy, and immunohistochemical analysis may be useful to differentiate solitary
      fibrous tumor of the pleura from mesothelioma and other similar tumors.

PMID- 24326858
TI  - The youth area project at the Centro di Riferimento Oncologico in Aviano.

PMID- 24326859
TI  - Adolescents with cancer in Italy: from local projects to a national coordinated
      program.

PMID- 24326860
TI  - Improving the outcome and reducing the risks of imaging-guided transthoracic
      biopsies of lung lesions.

PMID- 24326861
TI  - Off-label prescription of anti-cancer drugs in Italy: what responsibilities?

PMID- 24326862
TI  - Cost of illness in patients with multiple myeloma in Italy: the CoMiM study.
AB  - AIMS AND BACKGROUND: Multiple myeloma is the second most common hematological
      cancer. Although it accounts for only a relatively small percentage of all cancer
      types, the costs associated with managing multiple myeloma are considerable.
      Available studies are mainly focused on health care costs. The Costo del Mieloma
      Multiplo (Cost of MM, CoMiM) study investigated the cost of illness of multiple
      myeloma in Italy during one year of disease management. METHODS: CoMiM is a
      retrospective, prevalence-based, multi-center, cross-sectional study based on a
      stratified sample of patients seen during normal clinical practice (asymptomatic;
      symptomatic on drugs; symptomatic receiving autologous stem cell transplantation;
      plateau/remission). Demographics, clinical history, health care and non-health
      care resource consumption data were collected. Costs were evaluated from the
      societal viewpoint and expressed in Euro 2008. RESULTS: Data on 236 patients were
      analyzed (39 asymptomatic, 17%; 29 symptomatic receiving autologous stem-cell
      transplantation, 12%; 105 symptomatic receiving drugs, 44%; 63 plateau/remission,
      27%). The total cost of illness reached ? 19,267.1 +/- 25,078.6 (asymptomatic, ?
      959.3 +/- 1091.6; symptomatic receiving drugs, ? 21,707.8 +/- 21,785.3;
      symptomatic receiving autologous stem-cell transplantation, ? 59,243.7 +/-
      24,214.0; plateau/remission, ? 8130.7 +/- 15,092.5). The main cost drivers of
      total cost of illness were drugs and hospital admissions (46.1% and 29.4%,
      respectively). Antineoplastics and immunomodulators drove the cost of drugs
      (21.6% and 21.1% of the total cost of illness). Cost of antineoplastics was led
      by bortezomib (97.4%), whereas the cost driver for immunomodulators was
      lenalidomide (99.4%). Cost of hospitalization funded by the Italian National
      Health Service was strongly influenced by transplantation (94.6%), whereas
      chemotherapy and skeletal fractures did not exceed 1% and 2%, respectively.
      CONCLUSIONS: Despite some limitations, the CoMiM study provides Italian health
      care decision-makers with an insight into the stratified cost of illness of
      multiple myeloma patients.

PMID- 24326863
TI  - Exogenous spatial attention: evidence for intact functioning in adults with
      autism spectrum disorder.
AB  - Deficits or atypicalities in attention have been reported in individuals with
      autism spectrum disorder (ASD), yet no consensus on the nature of these deficits
      has emerged. We conducted three experiments that paired a peripheral precue with
      a covert discrimination task, using protocols for which the effects of covert
      exogenous spatial attention on early vision have been well established in
      typically developing populations. Experiment 1 assessed changes in contrast
      sensitivity, using orientation discrimination of a contrast-defined grating;
      Experiment 2 evaluated the reduction of crowding in the visual periphery, using
      discrimination of a letter-like figure with flanking stimuli at variable
      distances; and Experiment 3 assessed improvements in visual search, using
      discrimination of the same letter-like figure with a variable number of
      distractor elements. In all three experiments, we found that exogenous attention
      modulated visual discriminability in a group of high-functioning adults with ASD
      and that it did so in the same way and to the same extent as in a matched control
      group. We found no evidence to support the hypothesis that deficits in exogenous
      spatial attention underlie the emergence of core ASD symptomatology. 

PMID- 24326864
TI  - Solitary metastasis to the small bowel from primary adenocarcinoma of the lung.

PMID- 24326865
TI  - ERCC1 in advanced biliary tract cancer patients treated with chemotherapy:
      prognostic and predictive roles.
AB  - BACKGROUND: In oncology, we tend to look for factors that reflect better
      prognosis or predict response to treatments in order to make a selection from
      which patients will derive the benefit, avoiding futile therapies and/or
      toxicities. Definitive prognostic and predictive factors in advanced biliary
      cancer remain unknown. METHODS: We retrospectively analyzed all consecutive
      patients in our institution with advanced biliary tract cancer treated with
      palliative cisplatin plus gemcitabine. We evaluated the prognostic and predictive
      role of the immunohistochemistry (IHC) expression of ERCC1 (excision cross
      complementing gene-1) on tumor response and also examined several clinical and
      laboratory prognostic factors for overall survival. RESULTS: From January 2009 to
      July 2011, 72 patients were identified; their median overall survival was 9.5
      months. Independent variables associated with shorter survival identified by the
      multivariable Cox regression analysis were ECOG 2-3 (HR 8.4; 95% CI 3.4 to 20.7;
      p < 0.001) and Charlson Comorbidity Index >1 (HR 9.5; 95% CI 1.6 to 55.3; p =
      0.012). Pathology slides were available from 44 patients: 23 (52%) stained
      positive for ERCC1 on IHC (score >=0.5). In this subgroup, expression of ERCC-1
      was not prognostic and was not associated with either clinical benefit (partial
      response and stable disease) or tumor response (partial response only) to
      chemotherapy. CONCLUSIONS: In this cohort of unselected patients with advanced
      biliary tract cancer treated with first-line gemcitabine plus cisplatin, IHC
      expression of ERCC1 was not either predictive or prognostic. Patients with ECOG 2
      3 and/or multiple comorbidities had worse survival.

PMID- 24326866
TI  - Robotic selective neck dissection by a postauricular facelift approach:
      comparison with conventional neck dissection.
AB  - OBJECTIVES: The aim of this study was to investigate the feasibility and efficacy
      of robot-assisted neck dissection by a postauricular facelift approach in head
      and neck squamous cell carcinoma (HNSCC), compared with conventional neck
      dissection. STUDY DESIGN: Case series with chart review. SETTING: University
      tertiary care hospital. SUBJECTS AND METHODS: Thirty HNSCC patients with
      clinically node negative necks (cN0) who underwent robot-assisted selective neck
      dissection (SND) by a postauricular facelift approach (11 patients, 12 necks) or
      conventional neck dissection (19 patients, 21 necks). RESULTS: The mean age was
      lower in the robotic group (P = .030). However, the distributions of gender and
      TNM stage did not differ between the two groups. The robotic SND was completed
      successfully in all patients. The mean operative time was longer in the robotic
      group (215 +/- 56 min) than the conventional group (144 +/- 43 min) (P < .001).
      The mean numbers of lymph nodes removed were 25.0 +/- 7.4 and 28.9 +/- 8.2 in the
      robotic and conventional group, respectively (P = .192), and the number of lymph
      nodes removed at each level also did not differ between the 2 groups. In
      addition, there was no significant difference in postoperative complications
      between the 2 groups, but cosmetic satisfaction was higher in the robot group (P
      = .002). CONCLUSIONS: Robot-assisted SND by a postauricular facelift approach is
      comparable to conventional neck dissection in selected patients with cN0 HNSCC
      and results in excellent postoperative cosmesis.

PMID- 24326867
TI  - Modified hyoid suspension technique in the treatment of multilevel related
      obstructive sleep apnea.
AB  - OBJECTIVE: Using the Hormann technique of hyoid suspension in sleep apnea
      surgery, a steel wire is placed through the thyroid cartilage and slung around
      the hyoid bone. However, we experienced thyroid cartilage fracture by steel wire
      traction. A modification is presented to avoid thyroid cartilage fracture. STUDY
      DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND
      METHODS: Twenty-seven patients affected by obstructive sleep apnea syndrome
      underwent Hormann hyoid suspension. In 2 patients, the steel wire caused a
      fracture of the thyroid cartilage. The technique was therefore modified in 25
      subsequent patients. The wire is threaded through an adaptation titanium
      miniplate placed on the surface of the thyroid cartilage. RESULTS: The apnea
      hypopnea index decreased from 43.1 to 10.9/h. Nineteen patients (76%) met the
      criteria for a successful outcome. No complications related to this modification
      were noted. CONCLUSIONS: The Hormann hyoid suspension is a procedure that
      advances the hyoid bone to expand the airway, and its effectiveness has been
      proven previously. The modified hyoid suspension presented here promises similar
      results without the risk of serious complications such as thyroid cartilage
      fracture.

PMID- 24326868
TI  - A large juvenile xanthogranuloma within the tongue.

PMID- 24326869
TI  - Synthesis of 3-((trifluoromethyl)thio)indoles via a reaction of 2-alkynylaniline
      with trifluoromethanesulfanylamide.
AB  - 3-((Trifluoromethyl)thio)indoles can be synthesized by a palladium(II)-catalyzed
      reaction of 2-alkynylaniline with trifluoromethanesulfanylamide in the presence
      of bismuth(III) chloride. The presence of bismuth(III) chloride is crucial for
      the success of this transformation, which activates the
      trifluoromethanesulfanylamide during the reaction.

PMID- 24326870
TI  - Small molecule-based tandem solar cells with solution-processed and vacuum
      processed photoactive layers.
AB  - A tandem solar cell device whose sub-cells are fabricated exclusively from small
      molecules (SMs) through both solution-processed and vacuum-processed deposition
      techniques is described. The front sub-cell's active layer consists of a bulk
      heterojunction (BHJ) DPP(TBFu)2:PC70BM device while the back cell has a typical
      bilayer structure employing a 2,4-bis[4-(N,N-diisobutylamino)-2,6
      dihydroxyphenyl] squaraine (SQ) donor and a C60 acceptor. 

PMID- 24326871
TI  - shRNA-mediated GSTP1 gene silencing enhances androgen-independent cell line DU145
      chemosensitivity.
AB  - PURPOSE: Design short hairpin RNA (shRNA) interference sequence to silence
      glutathione S-transferase P1 (GSTP1) gene of androgen-independent prostate cancer
      cell line DU145, and then to explore its effect on sensitivity to
      chemotherapeutics. METHODS: Target sequence was picked up to form the shRNA.
      DU145 cell was divided into five groups according to the shRNA added for
      transfection: shRNA255, shRNA554, shRNA593, negative-shRNA and blank group.
      Fluorescence microscope was used to pick up the shRNA with the highest
      transfection ratio. Western blotting and RT-PCR were taken to pick up the shRNA
      with the best gene silencing result. 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyl
      tetrazolium bromide assay and terminal de-oxynucleotidyl transferase-mediated
      dUTP nick end-labeling assay were used to detect survival ratio and apoptosis
      ratio of DU145 administered of fluorouracil (5-FU) or paclitaxel (PA) at
      different concentrations before and after shRNA transfection. RESULTS: Three
      different shRNA oligonucleotides (shRNA255; shRNA554; shRNA593) targeting the
      coding sequence of GSTP1 mRNA and one negative control shRNA were constructed.
      The transfection ratio of shRNA554 (76.2 +/- 0.68 %) was higher than that of
      shRNA255 (63.3 +/- 1.04 %) (P < 0.01) or shRNA593 (72.7 +/- 0.33 %) (P < 0.01).
      After transfection of shRNA554, the mRNA and protein of level were the lowest, P
      < 0.01. The survival ratio of DU145 administered with 5-FU of different
      concentrations (30, 60, 120, 240 MUg/ml) declined after transfection (P < 0.01).
      Besides, the apoptosis ratio increased after transfection (P < 0.01). Similarly
      the survival ratio of DU145 administered with PA of different concentrations
      (0.2, 2, 10, 20 MUg/ml) declined (P < 0.01) and the apoptosis ratio increased (P
      < 0.01) after transfection. CONCLUSIONS: The gene GSTP1 silence via shRNA
      transfection to androgen-independent prostate cancer cell line DU145 enhances the
      sensitivity to chemotherapeutics.

PMID- 24326872
TI  - Caecum perforation after renal transplantation: a case report and review of
      literature.
AB  - Gastrointestinal (GI) complication used to be the second most common complication
      in renal transplant patients after infection (Bardaxoglou et al. in Transpl Int
      6(3):148-152, 1993). Review of transplant registry reveals that GI complication
      is no longer the second most common type of complication after renal transplant,
      but that it is still a common cause of significant amount of deaths in renal
      transplant recipients (De Bartolomeis et al. in Transpl Proc 37(6):2504-2506,
      2005). In a study of 1,515 adults with severe GI complication after renal
      transplant, Sarkio et al. (Transpl Int 17(9):505-510, 2004) reported that
      gastroduodenal ulcers followed by colon perforation were the two biggest groups
      of GI complications during the first year after renal transplantation. Colonic
      perforation is estimated to occur in about 1 % of all cases of renal transplant
      patients, and it does predispose to potentially fatal complication. About 50 % of
      all colonic perforation is due to complication of acute inflammation of
      diverticular disease (Bardaxoglou et al. in Transpl Int 6(3):148-152, 1993; Guice
      et al. in Am J Surg 138(1):43-48, 1979; Koneru et al. in Arch Surg 125(5):610
      613, 1990; Coccolini et al. in Transpl Proc 41(4):1189-1190, 2009). This is
      particularly so because these patients were previously exposed to uremia before
      transplantation which alters their protein metabolism hence interfering with
      tissue healing there after (Carson et al. in Ann Surg 188(1):109-113, 1978). GI
      complications including colon perforation after renal transplantation have effect
      on a patient's long-term survival (Gil-Vernet et al. in Transpl Proc 39(7):2190
      2193, 2007). Despite this, the role of renal transplantation medication compared
      to anatomic anomaly in GI complication has been equivocal.

PMID- 24326873
TI  - Economies of scale in federally-funded state-organized public health programs:
      results from the National Breast and Cervical Cancer Early Detection Programs.
AB  - This study investigates the existence of economies of scale in the provision of
      breast and cervical cancer screening and diagnostic services by state National
      Breast and Cervical Cancer Early Detection Program (NBCCEDP) grantees. A translog
      cost function is estimated as a system with input factor share equations. The
      estimated cost function is then used to determine output levels for which average
      costs are decreasing (i.e., economies of scale exist). Data were collected from
      all state NBCCEDP programs and District of Columbia for program years 2006-2007,
      2008-2009 and 2009-2010 (N = 147). Costs included all programmatic and in-kind
      contributions from federal and non-federal sources, allocated to breast and
      cervical cancer screening activities. Output was measured by women served, women
      screened and cancers detected, separately by breast and cervical services for
      each measure. Inputs included labor, rent and utilities, clinical services, and
      quasi-fixed factors (e.g., percent of women eligible for screening by the
      NBCCEDP). 144 out of 147 program-years demonstrated significant economies of
      scale for women served and women screened; 136 out of 145 program-years displayed
      significant economies of scale for cancers detected. The cost data were self
      reported by the NBCCEDP State programs. Quasi-fixed inputs were allowed to affect
      costs but not economies of scale or the share equations. The main analysis
      accounted for clustering of observations within State programs, but it did not
      make full use of the panel data. The average cost of providing breast and
      cervical cancer screening services decreases as the number of women screened and
      served increases. 

PMID- 24326874
TI  - Dual-phase cone-beam computed tomography to see, reach, and treat hepatocellular
      carcinoma during drug-eluting beads transarterial chemo-embolization.
AB  - The advent of cone-beam computed tomography (CBCT) in the angiography suite has
      been revolutionary in interventional radiology. CBCT offers 3 dimensional (3D)
      diagnostic imaging in the interventional suite and can enhance minimally-invasive
      therapy beyond the limitations of 2D angiography alone. The role of CBCT has been
      recognized in transarterial chemo-embolization (TACE) treatment of hepatocellular
      carcinoma (HCC). The recent introduction of a CBCT technique: dual-phase CBCT (DP
      CBCT) improves intra-arterial HCC treatment with drug-eluting beads (DEB-TACE).
      DP-CBCT can be used to localize liver tumors with the diagnostic accuracy of
      multi-phasic multidetector computed tomography (M-MDCT) and contrast enhanced
      magnetic resonance imaging (CE-MRI) (See the tumor), to guide intra-arterially
      guidewire and microcatheter to the desired location for selective therapy (Reach
      the tumor), and to evaluate treatment success during the procedure (Treat the
      tumor). The purpose of this manuscript is to illustrate how DP-CBCT is used in
      DEB-TACE to see, reach, and treat HCC. 

PMID- 24326876
TI  - [Formal sample size calculation and its limited validity in animal studies of
      medical basic research].
AB  - Animal studies are highly relevant for basic medical research, although their
      usage is discussed controversially in public. Thus, an optimal sample size for
      these projects should be aimed at from a biometrical point of view. Statistical
      sample size calculation is usually the appropriate methodology in planning
      medical research projects. However, required information is often not valid or
      only available during the course of an animal experiment. This article critically
      discusses the validity of formal sample size calculation for animal studies.
      Within the discussion, some requirements are formulated to fundamentally regulate
      the process of sample size determination for animal experiments. 

PMID- 24326875
TI  - Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of
      in vivo virulence or transmissibility.
AB  - Without baseline human immunity to the emergent avian influenza A(H7N9) virus,
      neuraminidase inhibitors are vital for controlling viral replication in severe
      infections. An amino acid change in the viral neuraminidase associated with drug
      resistance, NA-R292K (N2 numbering), has been found in some H7N9 clinical
      isolates. Here we assess the impact of the NA-R292K substitution on antiviral
      sensitivity and viral replication, pathogenicity and transmissibility of H7N9
      viruses. Our data indicate that an H7N9 isolate encoding the NA-R292K
      substitution is highly resistant to oseltamivir and peramivir and partially
      resistant to zanamivir. Furthermore, H7N9 reassortants with and without the
      resistance mutation demonstrate comparable viral replication in primary human
      respiratory cells, virulence in mice and transmissibility in guinea pigs. Thus,
      in stark contrast to oseltamivir-resistant seasonal influenza A(H3N2) viruses,
      H7N9 virus replication and pathogenicity in these models are not substantially
      altered by the acquisition of high-level oseltamivir resistance due to the NA
      R292K mutation. 

PMID- 24326877
TI  - Evaluation of the quality of endoscopically obtained esophageal biopsies in the
      dog.
AB  - OBJECTIVE: An important premise for obtaining diagnostically relevant histology
      specimens is an appropriate biopsy technique. Goal of this study was to determine
      if biopsies of adequate quality can be obtained from the canine esophagus at the
      gastro-esophageal junction (GEJ) during routine upper gastrointestinal endoscopy.
      MATERIAL AND METHODS: Over the course of one year, 58 dogs undergoing upper
      gastrointestinal endoscopy because of the presence of esophageal (n = 22) or
      gastrointestinal (n = 36) clinical signs were prospectively included. Five
      biopsies were repeatedly collected from the same dorsal and ventral locations of
      the GEJ, fixated individually in 4% neutral buffered formaldehyde, and evaluated
      histopathologically after standard preparation and haematoxylin and eosin
      staining. The presence of esophageal squamous epithelium with a basal cell layer
      and lamina propria mucosae in conjunction with foveolar columnar epithelium and
      cardiac glands, and the absence of fundic glands in one specimen, respectively,
      was judged as an adequately sampled biopsy. RESULTS: Adequately sampled biopsies
      were reported in 45 out of 58 dogs, with 31 samples originating from the dorsal
      GEJ, 36 samples originating from the ventral GEJ, and with 22 samples originating
      from both sites, respectively. The incidence of adequately sampled biopsies
      increased significantly over time (r = 0,22; p < 0,05), with these biopsies being
      reported significantly more often during the last 6 months compared to the first
      6 months of the study (p = 0,03). Histopathological evaluation of the esophageal
      squamous epithelium showed fibrosis, inflammation, elongation of the stromal
      papillae, and increased thickness of the basal cell layers in 14 out of 58 dogs.
      Stromal papillae of the ventral esophageal epithelium were significantly
      elongated in dogs with esophageal clinical signs compared to dogs with
      gastrointestinal clinical signs (p = 0,03). CONCLUSION AND CLINICAL RELEVANCE:
      After an initial learning phase adequate esophageal biopsies from the GEJ can be
      obtained in canine patients undergoing upper gastrointestinal endoscopy, and
      histological lesions can be found in these biopsies.

PMID- 24326878
TI  - [Sublumbar abscesses in the dog. Retrospective evaluation of 13 patients].
AB  - OBJECTIVE: Presentation of sublumbar abscesses in the dog with regard to
      diagnostic and therapeutic options as well as prognosis. MATERIAL AND METHODS:
      Retrospective evaluation of the data of 13 dogs, which were presented with
      sublumbar abscesses between 2002 and 2012. RESULTS: Young to middle-aged and
      middle to large breed dogs were mainly affected. The time until presentation
      varied from 1 day to 2 years. Symptoms were generally nonspecific. Computed
      tomography and sonography were normally applied for diagnosis. All dogs underwent
      surgery and several wound examinations; only in two cases was a single surgical
      intervention sufficient. In addition, after being discharged, ambulant post
      operative care was usually necessary for a considerable time. In two cases, plant
      foreign bodies could be identified as a cause of abscess formation, and in one
      case a prostatic abscess and a putative prostate carcinoma were present. After
      surgery, 12 of 13 dogs could be discharged. Nine of them showed an unremarkable
      healing process, one dog had a relapse followed by an unremarkable healing
      process, and one dog was euthanized at the request of the owners because of a
      putative relapse. One animal was lost to follow-up. One dog was euthanized after
      two surgical procedures. CONCLUSION AND CLINICAL RELEVANCE: Sublumbar abscesses
      are a rare, but a serious disease in veterinary medicine. Sectional imaging
      techniques and sonography are suitable for diagnosis. Treatment is often
      sophisticated and long-standing. However, with adequate treatment, the prognosis
      with regard to a complete convalescence is favorable. In most cases, the cause of
      abscess formation remains unclear.

PMID- 24326879
TI  - [Efficacy of doxycycline for treatment of chlamydiosis in flocks of racing and
      fancy pigeons].
AB  - OBJECTIVE: Evaluation of the clinical efficacy of doxycycline application via
      drinking water in the treatment of chlamydiosis in infected, clinically ill
      flocks of racing and fancy pigeons (Columba livia f. domestica) under field
      conditions. MATERIAL AND METHODS: In the scope of a field study, 13 pigeon flocks
      with clinically manifest ornithosis were treated over a period of 25 days with a
      novel doxycycline formulation via drinking water. Infection with Chlamydia
      psittaci had been confirmed beforehand by molecular-biological investigation of
      organ material from dissected pigeons in each flock. Therapeutic success was
      evaluated by PCR-analysis of triple swabs from 10 animals of each flock on day 25
      of treatment and 7 days after completion of the therapy, as well as by repeated
      individual and daily herd examination. RESULTS: The causative agent Chlamydia
      psittaci together with additionally documented atypical chlamydia species in six
      of the 13 flocks could thereby no longer be detected. Furthermore, a resolution
      of clinical symptoms was achieved in each of the treated pigeon flocks.
      CONCLUSION: Application of doxycycline in the described therapy regimen proved
      successful for the treatment of ornithosis. In addition, excellent acceptance and
      tolerance of the deployed formulation could be confirmed in praxis.

PMID- 24326880
TI  - [Disseminated intravascular coagulopathy in a dog with Angiostrongylus vasorum
      infection].
AB  - A 2-year-old female spayed Epagneul-Breton dog was presented with ecchymoses, but
      an undisturbed general condition. Clinical examination additionally revealed
      petechia and a haematoma. Travel history included Italy and Denmark. Laboratory
      abnormalities were moderate thrombocytopenia, prolonged PT, aPTT and TT, and
      elevated d-dimers. Initial therapy consisted of plasma transfusions, fluids,
      doxycycline and famotidine administration. Babesiosis, ehrlichiosis,
      leishmaniosis, dirofilariosis or anaplasmosis could not be confirmed. Abdominal
      ultrasound was unremarkable, while thoracic radiographs showed a
      bronchointerstitial pattern. Faecal samples collected over 3 days were positive
      for Angiostrongylus vasorum after examination using the Baermann lungworm test.
      The A. vasorum infection was successfully treated with fenbendazole, whereupon
      thrombocytopenia and prolonged coagulation times were resolved. In regions of low
      prevalence, an infection with A. vasorum should also be considered as a
      differential diagnosis in dogs with coagulation abnormalities. Respiratory signs
      can be absent with this disease. The patient may have acquired the infection
      abroad or in Germany.

PMID- 24326881
TI  - Co-occurrence of an intraventricular meningioma and cholesterol granuloma of the
      choroid plexus in a cat.
AB  - A 12-year-old domestic shorthair cat was presented with neurologic signs
      localized to the forebrain. Magnetic resonance imaging (MRI) of the brain
      revealed a space occupying lesion within the third and the lateral ventricles.
      The lesion had areas of disparate signal characteristics and exerted a mass
      effect on the surrounding parenchyma and ventricular system. The histologic
      examination identified the co-existence of two intraventricular masses: a
      meningioma and a choroid plexus cholesterol granuloma. 

PMID- 24326882
TI  - [Multiple myeloma with significant multifocal osteolysis in a dog without a
      detectible gammopathy].
AB  - Description of a variant of multiple myeloma in a dog lacking the gammopathy
      normally associated with this type of neoplasm. A Border Collie mongrel was
      presented with symptoms of progressive hind-leg weakness, lethargy and tiredness,
      which had started to appear 6 weeks previously. Radiographic examination showed
      small osteolytic areas in the spinal column, but also diffuse small areas of
      increased opacity as well as evidence of decreased bone density in the pelvis and
      of both femoral necks. Moderate regenerative anaemia, hypogammopathy and
      hypercalcaemia were diagnosed. Computed tomography scans displayed multifocal
      osteolysis and bone destruction in the skull, spinal column, scapulae, proximal
      humeri, pelvis and femoral necks. H&E staining of the biopsies showed bone
      destruction and monomorphic plasmacyotid cell populations, causing infiltrative
      bone marrow lesions and osteolysis. In many areas neoplastic plasma cell
      infiltration of the bone marrow was 70% and in some areas reached 100%. The
      diagnosis was non-secretory multiple myeloma without apparent secretion of
      paraproteins into the blood. 

PMID- 24326883
TI  - [Deafness in the dog and cat: aetiology, diagnostics and treatment].
AB  - Deafness is one of the most common sensory deficits in cats and dogs. Determining
      the scope and the cause of deafness is important for a possible therapy and can
      enable the handling of the animal by its owner as well as influence the decision
      about breeding with the affected animal. Electrodiagnostic testing using the
      brainstem auditory evoked response (BAER) enables an objective evaluation of the
      hearing function. Additionally, otoscopy and various diagnostic imaging
      techniques, including computed tomography, can help in determining the cause of
      deafness. While conductive deafness can often be treated, there is normally no
      satisfactory treatment for sensorineural deafness. In such cases, an important
      task of the attending veterinarian is to advise the owner on handling his/her
      animal. 

PMID- 24326884
TI  - Evaluation of coronary artery disease and cardiac morphology and function in
      patients with hypertrophic cardiomyopathy, using cardiac computed tomography.
AB  - Coronary artery disease and cardiac morphology and function were evaluated in 51
      patients with hypertrophic cardiomyopathy (HCM), without typical chest pain,
      using cardiac computed tomography (CT). This study investigated the prevalence of
      coronary artery disease, the indicators of obstructive coronary stenosis, and the
      magnitude of left ventricular (LV) hypertrophy. The patients' mean coronary
      artery calcium score was 198.8 +/- 312.0 and was positively correlated with the
      number of coronary risk factors (r = 0.32; P < 0.05). Of the 51 patients with
      HCM, 42 (82.4 %) had some degree of stenosis and 8 (15.7 %) had obstructive
      stenosis. Noncalcified and mixed plaques were detected in 14 (27.5 %) and 11
      (21.6 %) patients, respectively. Multivariate logistic regression revealed that
      diabetes was an independent indicator of the presence of obstructive stenosis in
      HCM patients. Multivariate linear regression revealed that low estimated
      glomerular filtration rates and high triglyceride concentrations were independent
      indicators of higher LV mass indexes. In conclusion, cardiac CT revealed that
      coronary artery disease was common among patients with HCM. The presence of
      obstructive coronary stenosis and the magnitude of LV hypertrophy were related to
      the presence of diabetes, triglyceride levels, and estimated glomerular
      filtration rate. 

PMID- 24326885
TI  - Does lean tissue mass accrual during adolescence influence bone structural
      strength at the proximal femur in young adulthood?
AB  - The purpose of this study was to identify whether young adult bone structural
      strength at the hip is associated with adolescent lean tissue mass (LTM) accrual.
      It was observed that those individuals who accrued more LTM from adolescence to
      adulthood had significantly greater adult bone structural strength at the hip.
      INTRODUCTION: The purpose of this study was to identify whether young adult bone
      cross-sectional area (CSA), section modulus (Z), and outer diameter (OD) at the
      hip were associated with adolescent LTM accrual. METHODS: One hundred three young
      adult participants (55 males, 48 females) were tertiled into adolescent LTM
      accrual groupings. LTM accrual was assessed by serial measures using dual energy
      X-ray absorptiometry (DXA) from adolescence to young adulthood (21.3 +/- 1.3
      years). CSA, Z, and OD at the narrow neck (NN) and femoral shaft (S) sites of the
      proximal femur were assessed in young adulthood (21.3 +/- 4.5 years), using hip
      structural analysis. Group differences were assessed using an analysis of
      covariance, controlling for adult height, weight, sex, and physical activity
      levels. RESULTS: It was found that individuals with higher adjusted adolescent
      LTM accrual had significantly greater adult adjusted values of NNCSA (2.49 +/-
      0.06 vs 2.77 +/- 0.07 cm(2)), NN Z (1.18 +/- 0.04 vs 1.37 +/- 0.04 cm(3)), NN OD
      (3.07 +/- 0.04 vs 3.21 +/- 0.04 cm), SCSA (3.45 +/- 0.08 vs 3.88 +/- 0.09 cm(3)),
      and SZ (1.77 +/- 0.05 vs 2.00 +/- 0.05 cm(3)) than individuals with lower LTM
      accrual (p < 0.05). CONCLUSIONS: These findings suggest that the amount of LTM
      accrued from adolescence to young adulthood has a positive influence on adult
      bone structural strength at the proximal femur.

PMID- 24326886
TI  - Evaluation of pre-hospital administration of adrenaline (epinephrine) by
      emergency medical services for patients with out of hospital cardiac arrest in
      Japan: controlled propensity matched retrospective cohort study.
AB  - OBJECTIVES: To evaluate the effectiveness of pre-hospital adrenaline
      (epinephrine) administered by emergency medical services to patients with out of
      hospital cardiac arrest. DESIGN: Controlled propensity matched retrospective
      cohort study, in which pairs of patients with or without (control) adrenaline
      were created with a sequential risk set matching based on time dependent
      propensity score. SETTING: Japan's nationwide registry database of patients with
      out of hospital cardiac arrest registered between January 2007 and December 2010.
      PARTICIPANTS: Among patients aged 15-94 with out of hospital cardiac arrest
      witnessed by a bystander, we created 1990 pairs of patients with and without
      adrenaline with an initial rhythm of ventricular fibrillation or pulseless
      ventricular tachycardia (VF/VT) and 9058 pairs among those with non-VF/VT. MAIN
      OUTCOME MEASURES: Overall and neurologically intact survival at one month or at
      discharge, whichever was earlier. RESULTS: After propensity matching, pre
      hospital administration of adrenaline by emergency medical services was
      associated with a higher proportion of overall survival (17.0% v 13.4%;
      unadjusted odds ratio 1.34, 95% confidence interval 1.12 to 1.60) but not with
      neurologically intact survival (6.6% v 6.6%; 1.01, 0.78 to 1.30) among those with
      VF/VT; and higher proportions of overall survival (4.0% v 2.4%; odds ratio 1.72,
      1.45 to 2.04) and neurologically intact survival (0.7% v 0.4%; 1.57, 1.04 to
      2.37) among those with non-VF/VT. CONCLUSIONS: Pre-hospital administration of
      adrenaline by emergency medical services improves the long term outcome in
      patients with out of hospital cardiac arrest, although the absolute increase of
      neurologically intact survival was minimal.

PMID- 24326887
TI  - Intravenous fluid therapy for adults in hospital: summary of NICE guidance.

PMID- 24326888
TI  - Adrenaline for out of hospital cardiac arrest?

PMID- 24326889
TI  - Sodium in drugs and hypertension.

PMID- 24326890
TI  - Who cares for the nine million displaced people of Syria?

PMID- 24326891
TI  - A fat chance of slimming.

PMID- 24326892
TI  - Regulatory authority reviews GMC decisions in Mid Staffordshire cases.

PMID- 24326893
TI  - UK doctors' regulator strikes off GP for persistent dishonesty.

PMID- 24326894
TI  - Ex vivo characterization of carotid plaques by intravascular ultrasonography and
      virtual histology: concordance with real plaque pathomorphology.
AB  - BACKGROUND: The purpose of this study was to evaluate the accuracy of carotid
      plaque characterisation by virtual histology using intravascular ultrasonography
      (VH-IVUS) by comparing the results with real morphology. METHODS: Following
      elective carotid endarterectomy (CEA), atherosclerotic plaques from 36 patients
      (19 asymptomatic, 17 symptomatic) underwent ex-vivo VH-IVUS examination.
      Afterwards, tissue specimens were fixed with formalin and embedded in paraffin.
      Atherosclerotic lesions were characterised following hematoxylin/eosin (HE) and
      Elastin van Gieson (EvG) staining using AHA classification (stages I to VIII).
      The plaque composition, cellularity, severity of inflammation, and atheroma
      associated macrophages and foam cells were compared with virtual histology.
      RESULTS: Patients with symptomatic carotid artery stenosis showed most commonly
      lesion type IV-V (N.=9; 52.9%), followed by type VI (N.=3; 17.6%) and type VII
      (N.=3, 17.6%), type VIII (N.=1; 5.9%) and type I-III (N.=1; 5.9%). In
      asymptomatic patients with the main lesion was type VII (N.=8; 42.1%), followed
      by type I-III (N.=4; 21.1%), type IV-V (N.=3, 15.8%) and type VIII (N.=1; 5.3%).
      The composition of unstable lesions differed significantly in symptomatic
      patients compared to asymptomatic subjects (70.1% vs. 31.6%, P=0.03). The
      concordance between the histological results and the VH-IVUS classification was
      86.1% (Cohen's kappa of 0.72). CONCLUSIONS: In the present study, our findings
      demonstrated significant correlation between true plaque composition determined
      by histology and VH-IVUS. Thus, IVUS might be useful as an additional diagnostic
      method to detect patients with unstable rupture-prone plaques.

PMID- 24326895
TI  - Endovascular versus surgical revascularization in proximal subclavian artery
      obstruction.
AB  - BACKGROUND: The aim of this paper was to compare the outcomes of endovascular
      versus surgical treatment in patients with symptomatic proximal subclavian artery
      obstruction through a retrospective clinical study. Treatment of symptomatic
      subclavian artery obstruction can be performed with percutaneous transluminal
      angioplasty or open surgical reconstruction. Comparative studies are scarce.
      METHODS: Technical success, patency and complication rates of 47 endovascular
      reconstructions in 46 patients were retrospectively compared with those of 19
      open surgical reconstructions in 17 patients performed between 1996 and 2012. An
      additional series of 51 surgical reconstructions performed in the same
      institution between 1976 and 1993 served as a reference. RESULTS: The technical
      success rate was 79% for endovascular and 100% for open surgical reconstructions
      (P<0.05). Primary patency was 72% and 89% at 1 year or 54% and 55% at 5 years for
      the endovascular and open surgical groups, respectively (log rank 0.210, P=0.65).
      Assisted primary patency was 77% and 100% at 1 year or 67% and 67% at 5 years,
      respectively (log rank 0.528, P=0.47). There was no mortality and major
      complications were infrequent, occurring equally in both groups (P=0.22).
      CONCLUSIONS: Although with its less invasive character endovascular treatment has
      gained preference over surgical treatment of proximal subclavian obstruction in
      many cases, extrathoracic surgical reconstruction can be performed with a higher
      technical success rate, similar patency and a comparable number of complications.

PMID- 24326896
TI  - Deformation and distensibility distribution along the abdominal aorta in the
      presence of aneurysmal dilatation.
AB  - BACKGROUND: In order to evaluate the elastic behavior of the abdominal aortic
      aneurysm (AAA), the distribution of aortic deformation during the cardiac cycle
      is measured. Moreover, the distensibility of the AAA composite structure
      consisting of the AAA wall and the intraluminal thrombus (ILT), as well as that
      of the adjacent non-aneurysmal aortic segment (NAA), are calculated. METHODS: Ten
      patients underwent electrocardiographically-gated computed tomography. 3D
      surfaces of aortic wall and lumen were reconstructed during peak-systole and end
      diastole and cross-sections perpendicular to the centerline were extracted 1 mm
      apart. Comparison of cross-sectional areas between peak-systole and end-diastole
      provided the relative area change (RAC). Mean values were calculated for NAA
      (RACNAA), aneurysmal wall (RACWall), and aneurysmal lumen (RACLumen).
      Distensibility of aneurysmal and unaffected aorta was calculated using brachial
      blood pressure measurements (DAAA and DNAA respectively). Normalized
      distensibility (DNORM) of the AAA was calculated with respect to normal aortic
      segment distensibility and related to aneurysm size and thrombus content.
      RESULTS: A map of aortic deformation during the cardiac cycle was obtained.
      Differences between RACWall (median=0.7%, range=0.3-2.1%) and both RACNAA
      (median=2.8%, range=0.9-4.8%) and RACLumen (median=1.8%, range=0.5-3.4%) were
      statistically significant. DAAA (median=0.30?10-5 Pa-1, range=0.05-0.64?10-5 Pa
      1) was lower than DNAA (median=0.43?10-5 Pa-1, range=0.16-0.83?10-5 Pa-1) but
      difference was not statistically significant. Median DNORM was 0.73 (range=0.1
      3.1) and presented a significant positive correlation with AAA size and thrombus
      content. CONCLUSIONS: Aneurysmal wall deforms significantly less than non
      aneurysmal wall and aneurysmal lumen, due to altered elastic properties and
      reduced loading. In large AAAs with larger amounts of ILT, the lumen deformation
      is comparable or even exceeds that of NAA and subsequently so does the
      distensibility of the Wall-ILT composite, an observation suggesting a thrombus
      cushioning effect. DNORM may provide insight in the estimation of AAA evolution
      and assist in rupture risk assessment.

PMID- 24326897
TI  - Exercise capacity and paroxysmal atrial fibrillation in patients with
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia among patients
      with hypertrophic cardiomyopathy (HCM). The relationship between paroxysmal AF
      and exercise capacity in this population is incompletely understood. METHODS:
      Patients with HCM underwent symptom-limited cardiopulmonary testing with expired
      gas analysis at Stanford Hospital between October 2006 and October 2012. Baseline
      demographics, medical histories and resting echocardiograms were obtained for all
      subjects. Diagnosis of AF was established by review of medical records and
      baseline ECG. Those with paroxysmal AF were in sinus rhythm at the time of
      cardiopulmonary testing with expired gas analysis. Exercise intolerance was
      defined as peak VO2<20 mL/kg/min. We used multivariate logistic regression to
      evaluate the association between exercise intolerance and paroxysmal AF. RESULTS:
      Among the 265 patients recruited, 55 had AF (28 paroxysmal and 27 permanent).
      Compared with those without AF, subjects with paroxysmal AF were older, more
      likely to use antiarrhythmic and anticoagulant medications, and had larger left
      atria. Patients with paroxysmal AF achieved lower peak VO2 (21.9+/-9.2 mL/kg/min
      vs 26.9+/-10.8 mL/kg/min, p=0.02) and were more likely to have exercise
      intolerance (61% vs 28%, p<0.001) compared with those without AF. After
      adjustment for age, sex and body mass index (BMI) exercise intolerance remained
      significantly associated with paroxysmal AF (OR 4.65, 95% CI 1.83 to 11.83,
      p=0.001). CONCLUSIONS: Patients with HCM and paroxysmal AF demonstrate exercise
      intolerance despite being in sinus rhythm at the time of exercise testing.

PMID- 24326898
TI  - Dabigatran in the setting of catheter ablation of atrial fibrillation: the road
      ahead. The authors' reply.

PMID- 24326899
TI  - Cardiac complications and manifestations of chemotherapy for cancer.

PMID- 24326900
TI  - Psychosocial benefits of cardiac rehabilitation among women compared with men.
AB  - PURPOSE: Cardiac rehabilitation (CR) has been shown to reduce cardiac risk and
      improve the psychosocial functioning of participants. This study examines gender
      differences on several psychosocial indicators across the course of CR. METHODS:
      Patients (N = 380; 67.9% men and 32.1% women) referred from local inpatient and
      outpatient settings at a southeastern US academic medical facility were assessed
      on reported levels of depression, anxiety, panic, anger, and relationship
      satisfaction, using the Burns Brief Mood Survey, at the start and conclusion of a
      CR program. Medical variables were also assessed but are not the focus of this
      report. Statistical analyses included 1-way, Kruskal-Wallis, and repeated
      measures analysis of variance procedures, as well as chi analyses. RESULTS: Women
      reported more psychosocial symptoms at pre-CR than men, and overall, both groups
      improved across CR. Women with significant depression, anxiety, and panic
      experienced clinically significant benefit across CR. Although the percentage of
      men reporting clinically significant levels of anger decreased significantly
      across CR, clinically significant levels of anger did not significantly change
      among women. In addition, women did not report benefits in relationship
      dissatisfaction. CONCLUSION: This study provides further evidence that CR offers
      psychosocial benefit for women, as has been reported in several small clinical
      samples. Some notable gender differences on anger and relationship satisfaction
      were observed. Clinical attention may be warranted to facilitate improvement for
      symptoms of anger and relationship concerns among selected women who participate
      in CR.

PMID- 24326901
TI  - Comorbidities and medication burden in patients with chronic obstructive
      pulmonary disease attending pulmonary rehabilitation.
AB  - PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by
      concomitant systemic manifestations and comorbidities such as cardiovascular
      disease. Little data exist on the prevalence of comorbidities and medication
      burden in people with COPD attending pulmonary rehabilitation (PR) programs in
      Australia. This study aimed to determine the prevalence of comorbidities and
      describe the type and number of medications reported in a sample of patients with
      COPD referred to PR. METHODS: A retrospective audit was conducted on patients
      referred to PR over a 1-year period. Data were collected on patient demographics,
      disease severity, comorbidities, and medications by review of patient notes,
      physician referral, and self-reported medication use. RESULTS: Data were
      available on 70 patients (forced expiratory volume in 1 second = 37.5 [26.0] %
      predicted). Ninety-six percent of patients had at least 1 comorbidity, and 29%
      had 5 or more. The most common comorbidities were associated with cardiovascular
      disease (64% of patients). Almost half of the sample was overweight or obese
      (49%). Prescription medication use was high, with 57% using between 4 and 7
      medications, and 29% using 8 or more. CONCLUSIONS: Patients with COPD attending
      PR in Australia have high rates of comorbidity. The number of medications
      prescribed for these individuals is similar to that seen in other chronic disease
      states such as chronic heart failure. Pulmonary rehabilitation presents
      opportunities for clinicians to educate patients on self-management strategies
      for multiple comorbidities, review medication usage, and discuss strategies aimed
      at optimizing adherence with medication regimes.

PMID- 24326902
TI  - Examining the steps-per-day trajectories of cardiac rehabilitation patients: a
      latent class growth analysis perspective.
AB  - PURPOSE: Research suggests that cardiac rehabilitation (CR) patients need to
      engage in at least 6500 steps per day to obtain health benefits. Unfortunately,
      very little is known about the steps-per-day trajectories of these patients and
      whether the demographic, clinical, and CR program characteristics are similar for
      these trajectories. METHODS: Patients (n = 235) completed a questionnaire
      assessing demographic and clinical variables upon entry to CR and subsequently
      wore a pedometer for 7 days at the end of CR, and 3, 6, and 9 months after
      completing CR. RESULTS: Latent class growth analyses showed that 3 classes of
      patients emerged that were termed nonadherers (averaged ~3112 steps per day at
      the end of CR and remained stable up to 9 months after CR), significant decliners
      (averaged ~7010 steps per day at the end of CR and steadily declined after CR),
      and optimal adherers (averaged ~10 700 steps per day and remained stable after
      CR). Logistic regressions showed that nonadherers were more likely to be obese,
      have at least 1 comorbidity, and a lower exercise capacity compared with the
      significant decliners/optimal adherers. CONCLUSIONS: Distinct steps-per-day
      trajectories exist for CR patients that are partially distinguished by
      demographic and clinical variables.

PMID- 24326904
TI  - Electrification of wind-blown sand: recent advances and key issues.
AB  - In this paper, we summarize the recent advances on the electrification of wind
      blown sand. Some of the outstanding questions, such as the interpretation of the
      electrification of wind-blown sand, measurements on and models of the features of
      the wind-blown sand E-fields, as well as their effect on the wind-blown sand flux
      and electromagnetic wave propagation, are reviewed. We end by highlighting the
      challenges that remain. 

PMID- 24326903
TI  - The epidemiology of occupational heat exposure in the United States: a review of
      the literature and assessment of research needs in a changing climate.
AB  - In recent years, the United States has experienced record-breaking summer heat.
      Climate change models forecast increasing US temperatures and more frequent heat
      wave events in the coming years. Exposure to environmental heat is a significant,
      but overlooked, workplace hazard that has not been well-characterized or studied.
      The working population is diverse; job function, age, fitness level, and risk
      factors to heat-related illnesses vary. Yet few studies have examined or
      characterized the incidence of occupational heat-related morbidity and mortality.
      There are no federal regulatory standards to protect workers from environmental
      heat exposure. With climate change as a driver for adaptation and prevention of
      heat disorders, crafting policy to characterize and prevent occupational heat
      stress for both indoor and outdoor workers is increasingly sensible, practical,
      and imperative. 

PMID- 24326905
TI  - On the determination of a generalized Darcy equation for yield-stress fluid in
      porous media using a Lattice-Boltzmann TRT scheme.
AB  - Simulating flow of a Bingham fluid in porous media still remains a challenging
      task as the yield stress may significantly alter the numerical stability and
      precision. We present a Lattice-Boltzmann TRT scheme that allows the resolution
      of this type of flow in stochastically reconstructed porous media. LB methods
      have an intrinsic error associated to the boundary conditions. Depending on the
      schemes this error might be directly linked to the effective viscosity. As for
      non-Newtonian fluids viscosity varies in space the error becomes inhomogeneous
      and very important. In contrast to that, the TRT scheme does not present this
      deficiency and is therefore adequate to be used for simulations of non-Newtonian
      fluid flow. We simulated Bingham fluid flow in porous media and determined a
      generalized Darcy equation depending on the yield stress, the effective
      viscosity, the pressure drop and a characteristic length of the porous medium. By
      evaluating the flow in the porous structure, we distinguished three different
      scaling regimes. Regime I corresponds to the situation where fluid is flowing in
      only one channel. Here, the relation between flow rate and pressure drop is given
      by the non-Newtonian Poiseuille law. During Regime II an increase in pressure
      triggers the opening of new paths and the relation between flow rate and the
      difference in pressure to the critical yield pressure becomes quadratic:
      [Formula: see text]. Finally, Regime III corresponds to the situation where all
      the fluid is flowing. In this case, [Formula: see text]. 

PMID- 24326906
TI  - Convolution theory for dynamic systems: a bottom-up approach to the
      viscoelasticity of polymeric networks.
AB  - Biological materials such as the cytoskeleton are characterized by remarkable
      viscoelastic properties and therefore represent the subject of numerous micro-
      and macrorheological experimental studies. By generalizing the previously
      introduced dynamic convolution theory (DCT) to two dimensions, we devise a bottom
      up approach for the viscoelastic properties of extended, crosslinked semiflexible
      polymer networks. Brownian dynamics (BD) simulations serve to determine the
      dynamic linear self- and cross-response properties of isolated semiflexible
      polymers to externally applied forces and torques; these response functions are
      used as input to the DCT. For a given network topology, the frequency-dependent
      response of the network subject to a given external force/torque distribution is
      calculated via the DCT allowing to resolve both micro- and macrorheological
      properties of the networks. A mapping on continuum viscoelastic theory yields the
      corresponding viscoelastic bulk moduli. Special attention is drawn to the
      flexibility of crosslinkers, which couple angular degrees of freedom at the
      network nodes and which are found to sensitively affect the resulting rheological
      properties of the polymeric meshwork. 

PMID- 24326907
TI  - Different bacterial communities in ectomycorrhizae and surrounding soil.
AB  - Several eukaryotic symbioses have shown to host a rich diversity of prokaryotes
      that interact with their hosts. Here, we study bacterial communities associated
      with ectomycorrhizal root systems of Bistorta vivipara compared to bacterial
      communities in bulk soil using pyrosequencing of 16S rRNA amplicons. A high
      richness of Operational Taxonomic Units (OTUs) was found in plant roots (3,571
      OTUs) and surrounding soil (3,476 OTUs). The community composition differed
      markedly between these two environments. Actinobacteria, Armatimonadetes,
      Chloroflexi and OTUs unclassified at phylum level were significantly more
      abundant in plant roots than in soil. A large proportion of the OTUs, especially
      those in plant roots, presented low similarity to Sanger 16S rRNA reference
      sequences, suggesting novel bacterial diversity in ectomycorrhizae. Furthermore,
      the bacterial communities of the plant roots were spatially structured up to a
      distance of 60 cm, which may be explained by bacteria using fungal hyphae as a
      transport vector. The analyzed ectomycorrhizae presents a distinct microbiome,
      which likely influence the functioning of the plant-fungus symbiosis.

PMID- 24326909
TI  - A method based on impedance spectroscopy to determine transport properties of
      polymer electrolytes.
AB  - In this work, we introduce a method based on impedance spectroscopy and the
      equations developed to evaluate, with a good degree of accuracy, the number
      density, mobility and diffusion coefficient of mobile ions. Nyquist plots of
      electrolytes based on poly(acrylonitrile) or PAN and methyl cellulose (MC)
      incorporated with lithium bis(oxalato)borate have been established from impedance
      measurements. Equivalent circuits based on a resistor and "leaky capacitor(s)"
      have been determined and the relevant impedance equations derived. The values of
      the parameters required in the equation are obtained from the Nyquist plots and
      the parameters that cannot be obtained from the respective plots have been
      obtained by trial and error in order to fit the Nyquist plots. The transport
      parameters are calculated using the developed equations and the results have been
      compared with those obtained from the broadband dielectric response (BDR) method.
      Finally, Fourier transform infrared (FTIR) spectroscopy has been used to verify
      the results obtained from the two approaches at room and elevated temperatures. 

PMID- 24326908
TI  - Measurement of mealtime behaviors in rural overweight children: an exploratory
      factor analysis of the Behavioral Pediatrics Feeding Assessment Scale.
AB  - OBJECTIVE: The current study presents results of an exploratory factor analysis
      (EFA) of the Behavioral Pediatric Feeding Assessment Scale (BPFAS) in a sample of
      rural children with overweight and obesity. Relationships between mealtime
      behavior and health outcomes are also explored. METHODS: EFA was used to assess
      the fit of the BPFAS in a group of 160 treatment-seeking children (Mage = 9.11,
      SD = 1.77) living in rural Midwest communities. Correlations were also computed
      between factor scores and select health variables (child body mass index z-score
      and diet variables). RESULTS: The EFA identified a 5-factor solution as the best
      fitting model (Tucker-Lewis Index = .96, root mean square error of approximation
      = .05), although several items (i.e., 7 of 25) did not load on any factor. 2
      factors were correlated with health variables of interest. CONCLUSION: Study
      results suggest that certain items on the BPFAS may not be appropriate for use
      with rural children with pediatric overweight or obesity. Implications for future
      research and practice are discussed.

PMID- 24326910
TI  - A novel inducible expression system for the functional study of toxic gene in
      bacteria.
AB  - The cloning and expression of toxic proteins in bacteria have posed a great
      challenge because of the leaky expression in inducible expression systems. Using
      artificial gene synthesis and clone screening methods, we identified a mutant T5
      promoter, which significantly reduced leaky expression of lac operator. The
      mutant T5 promoter contains two T deletions at -35 region and may reduce promoter
      activity. A bacterial lethal gene, Phi174 lytic gene E, was successfully cloned
      in this system and expressed in the presence of isopropyl beta-D-1
      thiogalactopyranoside. The system is compatible with existing T5 inducible
      expression systems and can be used for the controlled expression of toxic
      proteins. 

PMID- 24326911
TI  - Isolation and characterization of xanthan-degrading Enterobacter sp. nov. LB37
      for reducing the viscosity of xanthan in petroleum industry.
AB  - A Gram-negative, straight rod and facultative anaerobic bacterium was isolated
      from soil sample. It exhibits the phenotypic characteristics consistent with its
      classification in the genus Enterobacter. The isolate ferment glucose to acid and
      gas. Arginine dihydrolase, ornithin decarboxylase and gelatinase but not
      deoxyribonuclease was produced by this isolate. There was no hydrogen sulfide
      production. On the basis of the phenotypic data, together with phylogenetic
      analysis based on 16S rDNA gene sequences, this strain should represent a novel
      species of the genus Enterobacter and was designated as LB37. The strain LB37
      could degrade xanthan molecules resulting in the rapid decrease of the viscosity
      of xanthan solution used in oil drilling process. Endoxanthanase activity was
      also detected in the culture supernatant. To our knowledge, it is the first
      report on the microbes being involved in the xanthan degradation for oil
      industry. The isolate LB37 would be useful for potential application in enhanced
      oil recovery and oil drilling field. 

PMID- 24326912
TI  - Total prohibition of smoking but not partial restriction effectively reduced
      exposure to tobacco smoke among restaurant workers in Finland.
AB  - OBJECTIVES: To assess work-related exposure to tobacco smoke in Finnish
      restaurants, a series of nationwide questionnaire surveys were conducted among
      restaurant workers and the levels of indoor air nicotine concentrations were
      measured in restaurants. The survey aimed to evaluate the impact of the smoke
      free legislation in general and in particular after the total smoking ban
      launched in 2007. MATERIALS AND METHODS: In 2003-2010, four national
      questionnaire surveys were conducted among restaurant workers and the
      concentration of nicotine in indoor air was measured in different types of
      restaurants, bars and nightclubs. RESULTS: Between 2003 and 2010, the proportion
      of restaurant workers reporting occupational exposure to tobacco smoke dropped
      from 59% to 11%. Among pub workers, the decrease was from 97% to 18% and in
      workers of dining restaurants from 49% to 10%, respectively. The median
      concentration of nicotine in indoor air of all restaurants decreased from 11.7
      MUg/m(3) to 0.1 MUg/m(3). The most significant decrease was detected in pubs
      where the decrease was from 16.1 MUg/m(3) to 0.1 MUg/m(3). Among all restaurant
      workers, in 2003-2010 the prevalence of daily smokers was reduced from 39% to 31%
      in men and from 35% to 25% in women. CONCLUSION: Total prohibition of smoking but
      not partial restriction in restaurants was effective in reducing work-related
      exposure to tobacco smoke. Strict tobacco legislation may partly be associated
      with the significant decrease of daily smoking prevalence among restaurant
      workers.

PMID- 24326913
TI  - Assessment of 8-oxo-7,8-dihydro-2'-deoxyguanosine as a marker of oxidative DNA
      damage in gasoline filling station attendants.
AB  - OBJECTIVES: The urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxodG) was used as a biomarker of oxidative DNA damage. The urinary 8-oxodG
      levels in petrol filling station attendants (exposed) at various petrol bunks
      were estimated as well as in the unexposed (cashier) population. MATERIALS AND
      METHODS: A total of 100 workers (79 petrol fillers and 21 cashiers) aged from 20
      to 41 years participated in the study. An informed consent was taken from each
      participant. Information on personal habits and health was obtained through a
      questionnaire. After shifts, urine samples were collected analyzed for 8-oxodG
      using enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty-three percent of
      workers were in the 21-30 years age group. The maximum level of 8-oxodG was
      observed in the age group >= 41 years and the minimum in the age group of 31-40
      years. The maximum level of 8-oxodG was observed among those workers who had >=
      21 years of experience. The concentrations of 8-oxodG were significantly higher
      in petrol fillers than those in cashiers (p < 0.05). CONCLUSIONS: Despite the
      conflicting results obtained in our study it was shown that 8-oxodG is related to
      chemical exposure. Further research is needed embracing a bigger number of
      participants to highlight the correlations between the exposure and the effects.

PMID- 24326914
TI  - Ceci tuera cela and disruptive technologies.

PMID- 24326915
TI  - Issues affecting the motivation of nuclear medicine technologists in Kuwait.
AB  - The demand for nuclear medicine technologists (NMTs) in Kuwait has increased,
      especially with the introduction of multimodality imaging systems. In order to
      increase the number of NMTs in the workforce and retain the existing NMTs, there
      should be a better way to motivate them. AIM: To find out how satisfied NMTs are
      and the factors that motivate them. METHODS: An interview was conducted with 40
      randomly selected NMTs to explore deep-seated emotions and attitudes that were
      related to motivation. Questions about the recognition NMTs receive from the
      general public, whether they are acknowledged as significant contributors to
      health services, ways to improve the standing of NMTs in society, and the clarity
      of the job description were included. A questionnaire survey was then conducted
      with 100 randomly selected NMTs. The questions were designed to elicit wider
      perspective of the information obtained from the interviews. RESULTS: The results
      show a need for attention in the Ministry of Health to NMTs for recognition,
      motivation, and improvement. Giving the NMTs their own identity and opportunities
      to be part of decision-making in the health team would influence more students to
      join nuclear medicine departments and give more self-confidence to the existing
      NMTs.

PMID- 24326916
TI  - Jefferson interprofessional clinical rounding project: an innovative approach to
      patient care.
AB  - BACKGROUND: Bedside rounding is an historical clinical model that brings together
      care providers and the patient to discuss the plan of care. Interprofessional
      clinical rounding is an approach that uses this historical model to involve
      multiple health professions. This study was conducted to determine if a model of
      interprofessional clinical rounding could be implemented successfully in an acute
      care setting. METHODS: Teams consisting of medical, nursing, and pharmacy
      students were assigned to work with the attending physician (AP) in the
      colorectal surgery service. Prior to the rounding experience, students met to
      review and discuss patients' data from their discipline-specific perspective and
      then made a presentation of the case to the AP, who used these presentations as
      an educational opportunity, asking probing questions. A structured observation
      form was used to assess the team members' interaction during this process, and a
      debriefing was held at the conclusion of each experience. FINDINGS: Results of
      the observations suggested that most students were very engaged in the process,
      while summaries of the debriefing revealed a high level of satisfaction among
      participants. All groups suggested that they had a better understanding of the
      roles of other professions as a result of the increased communication and claimed
      that the process resulted in a more patient-centered approach. They also claimed
      that the additional information provided through the team approach resulted in a
      more integrated plan of care because input is provided from these different
      perspectives. CONCLUSION: Interprofessional bedside rounding can be implemented
      successfully, resulting in a more effective experience for health professions
      students.

PMID- 24326917
TI  - Dissecting first-year students' perceptions of health profession groups:
      potential barriers to interprofessional education.
AB  - BACKGROUND: Previous research has shown that health profession students enter
      interprofessional education (IPE) programs with negative perceptions of health
      disciplines other than their own, which could serve as possible barriers to
      engagement with interprofessional principles. Yet, past studies have not fully
      dissected these perceptions, nor have they examined how these perceptions may
      contrast with how students view their own future profession. METHODS/FINDINGS: A
      total of 638 students from six different health profession training programs
      completed surveys assessing their perceptions/stereotypes of their own and other
      health professions. ANOVA and MANCOVA analyses showed a high degree of
      variability in how each profession is perceived by the students, but that the
      students, regardless of discipline (except medical students), rated their own
      profession the highest on almost every attribute listed. CONCLUSIONS: The data
      provide evidence for the tenets of Social Identity Theory raised in the relevant
      literature. The authors also suggest that the lack of adequately formulated
      "professional-in-training" identity, as well as the formidability of anticipatory
      socialization, help to foster and perpetuate these stereotypes and that IPE
      programs have the potential to exacerbate these negative perceptions.

PMID- 24326918
TI  - Student performance and satisfaction for a musculoskeletal objective structured
      clinical examination.
AB  - BACKGROUND: The reliability and validity of various Objective Structured Clinical
      Examinations (OSCEs) have been well documented in the medical and nursing
      literature. The purpose of this study was to examine the effect of exam
      preparation methods on student performance and student satisfaction for an OSCE
      used to assess doctoral physical therapist students. SUBJECTS: Sixty-five
      physical therapist students from two post-professional physical therapist
      programs were randomized to a rubric exam preparation group and a nonrubric exam
      preparation group for a musculoskeletal OSCE. METHODS: The OSCE was a midterm
      practical exam for a peripheral joint musculoskeletal course. Upon completion of
      the exam, all students completed a post-exam satisfaction survey. RESULTS: The
      results of the 2 x 2 ANCOVA that examined performance and satisfaction on the
      OSCE indicated a significant interaction between the group assignment and
      program, p<0.028, for performance, and that satisfaction scores between the
      rubric and nonrubric groups and program were not significant for any of the
      questions asked on the post-examination survey. CONCLUSION: Despite the reported
      benefit of utilizing rubrics, the findings of this study did not show a
      difference in student performance or satisfaction when using a rubric to prepare
      for an OSCE.

PMID- 24326919
TI  - Learning Style of Undergraduate Allied Health Students: clinical versus
      classroom.
AB  - BACKGROUND: Recognizing and valuing the diversity of student learning and
      learning styles allow educators to construct more effective and efficient
      teaching methods and create mutually beneficial learning environments. METHODS:
      Kolb(s Learning Style Inventories (LSI) were administered to 82 seniors enrolled
      in a School of Allied Health at a large midwestern university. The students
      completed LSI in relation to both their didactic and clinical coursework. Sets of
      instruments were matched and evaluated using descriptive statistics. RESULTS:
      Overall, in the didactic classroom setting, 24.2% (n=16) of the students were
      divergers, 28.8% (n=19) were accommodators, 19.4% (n=13) were convergers, and
      27.3% (n=18) were assimilators. In the clinical settings, 27.8% (n=20) of the
      students were divergers, 36.1% (n=26) were accommodators, 23.6% (n=17) were
      convergers, and only 12.5% (n=9) were assimilators. Learning style did change for
      66.7% (n=10) of athletic training majors. Over half of the students in medical
      dietetics, radiological sciences, and respiratory therapy LSIs did not change
      from classroom to clinical. CONCLUSION: The diverse nature of the students'
      preferences reinforces the need for various teaching strategies. Both the
      students and the educators need to work cooperatively to maximize the balance of
      the learning environment and make meaning of the educational experience.

PMID- 24326920
TI  - The standardized patient encounter: a dynamic educational approach to enhance
      students' clinical healthcare skills.
AB  - Occupational therapy educators are challenged to prepare students entering the
      profession to be skilled in assessment, critical thinking, self-analysis, and
      decision-making. Simulation is an effective strategy used in medical and nursing
      curriculums to develop or enhance critical thinking, self-analysis, and decision
      making skills. Through simulated learning activities, such as encounters with
      standardized patients (SP), students develop skills in decision-making, clinical
      reasoning, and interpersonal communication, skills necessary to function
      effectively in the current health care environment. This paper describes the
      process for integrating SP encounters in a professional healthcare curriculum for
      occupational therapy graduate students. Evidence that supports the use of
      simulation in healthcare curriculums for health profession students is explored.
      An example of an SP encounter in one occupational therapy course is described to
      illustrate how students engage in higher-level thinking as they administer an
      assessment tool and interact with an SP. The process of developing and evaluating
      the SP encounter is described and the outcomes are presented. The authors believe
      the SP experience is a viable teaching method in preparing competent, reflective
      practitioners for tomorrow's healthcare environment. 

PMID- 24326921
TI  - Sitting and cardiometabolic risk factors in U.S. adolescents.
AB  - PURPOSE: To examine sitting time and cardiometabolic disease risk in US
      adolescents. METHODS: Data from the 2007-2008 National Health and Nutrition
      Examination Survey (NHANES) were utilized. Self-reported daily sitting was
      ascertained by total time in seated activities. Cardiometabolic disease risk was
      defined by using age- and sex-specific metabolic syndrome (MetS), continuous
      metabolic risk score, and individual risk factors. RESULTS: There were 394
      adolescents (12-20 yrs) meeting the inclusion criteria. Mean age (+/- SE) was
      16.1 +/- 0.1 yrs and 51% were male. Mean daily sitting time (+/- SE) was 407 +/-
      11 min/day(6.8 hrs/day) and prevalence of MetS was 8.3%. Adolescents in the
      highest tertile for sitting time were more likely to be overweight/obese (42%)
      than adolescents in the other tertiles (22-28%). Multivariate regression analyses
      revealed that daily sitting time was not associated with MetS (odds ratio 0.94,
      95%CI 0.80-1.11) or the continuous risk score (b=0.02, SE=0.03, p=0.44). However,
      daily sitting time was positively correlated with insulin resistance (HOMA-IR)
      (b=0.03, SE=0.04, p=0.04); this association was attenuated after accounting for
      adiposity (sum of skinfolds), diet, and physical activity (b=0.04, SE=0.03,
      p=0.21). CONCLUSION: In adolescents, daily sitting time was not associated with
      MetS but was positively associated with fasting insulin resistance, although this
      relationship appears to be secondary to the influence of adiposity.

PMID- 24326922
TI  - Supervising allied health assistants: a concerning skill gap in allied health
      professionals.
AB  - The purpose of this paper is to identify and discuss the problem of a skill gap
      in the training of allied health professionals. Allied health assistants are
      required to work under the supervision of allied health professionals. There is
      little evidence to suggest supervisory skills are routinely taught as part of the
      development of professional behavior. With increasing concern about a lack of
      supervisory skill, there is an opportunity for supervisory skills to be
      incorporated into the undergraduate curriculum. A combination of classroom and
      clinical experience is required to ensure this professional skill does not
      continue to be overlooked. 

PMID- 24326923
TI  - Learning style preferences and academic success of preclinical allied health
      students.
AB  - Student learning style modality preferences, in preclinical classes, were
      assessed using the visual-aural-read/write-kinesthetic (VARK) inventory.
      Preferences were assessed for 137 preclinical students, including those in
      nursing, physician's assistant, physical therapy, athletic training, and natural
      science programs using the online VARK inventory. All classes contained a
      majority of multimodal and a significantly high proportion of kinesthetic
      learners. No correlations were noted between modality preference strength and
      assessment performance in general biology classes; significant correlations were
      discovered for kinesthetic preference among the same cohort in subsequent human
      anatomy (negative correlation) and general physiology (positive correlation)
      classes. Assessment performance of nursing students in an anatomy and physiology
      class resulted in correlations with aural (negative correlation) and visual
      (positive correlation) preference strengths. Study findings are used to evaluate
      the efficacy of non-omnimodal delivery of content-focused science classes, before
      the students have developed the background knowledge or skills required to
      contextualize the learning. 

PMID- 24326924
TI  - Interdisciplinary group learning in a kinesiology course: a novel approach.
AB  - This paper describes an active, collaborative learning project that occurred
      during a kinesiology course for first-year graduate students in physical (PT) and
      occupational therapy (OT) that was taught by faculty from both disciplines and
      designed to promote teamwork and integration of kinesiology concepts. The project
      required the students to describe and illustrate an assigned functional task,
      including the involved bony structure, joint mechanics, and muscle actions for
      joints of the lower extremities. Students from the PT and OT cohorts were
      intentionally mixed into groups of five students. They were provided with a topic
      for the assignment and a clear grading rubric. Each group gathered information
      from a variety of sources to address the topic. The final project was a poster
      that was presented to the class through an elaborate schedule that required all
      members of an individual group to present their poster to the group when they
      arrive at their poster. The presentations were well done and received high marks
      overall. Student scores were much less critical than faculty scores and included
      very few comments. The high scores awarded by course faculty indicated the
      thoroughness of the detail in the posters, as well as the preparedness of the
      students. An informally determined majority of students commented that being
      required to present the entire poster required them to comprehend material from
      the entire course, which we viewed as a positive learning experience. 

PMID- 24326925
TI  - Innovating in teaching collaborative practice with a large student cohort at
      Universite de Montreal.
AB  - Universite de Montreal implemented an interprofessional education (IPE)
      curriculum on collaborative practice in a large cohort of students (>1,100) from
      10 health sciences and psychosocial sciences training programs. It is made up of
      three one-credit undergraduate courses (CSS1900, CSS2900, CSS3900) spanning the
      first 3 years of training. The course content and activities aim for development
      of the six competency domains identified by the Canadian Interprofessional Health
      Collaborative. This paper describes the IPE curriculum and highlights the
      features contributing to its success and originality. Among main success key
      factors were: administrative cooperation among participating faculties, educators
      eager to develop innovative approaches, extensive use of clinical situations
      conducive to knowledge and skill application, strong logistic support, close
      cooperation with health care delivery organizations, and partnership between
      clinicians and patients. A distinguishing feature of this IPE curriculum is the
      concept of partnership in care between the patient and caregivers. Patients'
      representatives were involved in course planning, and patients were trained to
      become patients-as-trainers and cofacilitate interprofessional discussion
      workshops. They give feedback to students regarding integration and application
      of the patient partnership concept from a patient's point of view. 

PMID- 24326926
TI  - Production and purification of non replicative canine adenovirus type 2 derived
      vectors.
AB  - Adenovirus (Ad) derived vectors have been widely used for short or long-term gene
      transfer, both for gene therapy and vaccine applications. Because of the frequent
      pre-existing immunity against the classically used human adenovirus type 5,
      canine adenovirus type 2 (CAV2) has been proposed as an alternative vector for
      human gene transfer. The well-characterized biology of CAV2, together with its
      ease of genetic manipulation, offer major advantages, notably for gene transfer
      into the central nervous system, or for inducing a wide range of protective
      immune responses, from humoral to cellular immunity. Nowadays, CAV2 represents
      one of the most appealing nonhuman adenovirus for use as a vaccine vector. This
      protocol describes a simple method to construct, produce and titer recombinant
      CAV2 vectors. After cloning the expression cassette of the gene of interest into
      a shuttle plasmid, the recombinant genomic plasmid is obtained by homologous
      recombination in the E. coli BJ5183 bacterial strain. The resulting genomic
      plasmid is then transfected into canine kidney cells expressing the complementing
      CAV2-E1 genes (DK-E1). A viral amplification enables the production of a large
      viral stock, which is purified by ultracentrifugation through cesium chloride
      gradients and desalted by dialysis. The resulting viral suspension routinely has
      a titer of over 10(10) infectious particles per ml and can be directly
      administrated in vivo. 

PMID- 24326927
TI  - Ringette-related injuries in young female players.
AB  - OBJECTIVE: To document the injuries sustained during organized ringette games.
      DESIGN: Retrospective data. SETTING: Canadian Children's Hospital Emergency
      Department. PATIENTS: Information reported by the Canadian Hospitals Injury
      Reporting Prevention Program on the injuries of 494 female ringette players (age,
      10-17 years) between 2004 and 2010. ASSESSMENT OF RISK FACTORS: The injuries
      (types, body part, and mechanisms) presenting to emergency departments were
      compared between the 4 levels of minor organized ringette. MAIN OUTCOME MEASURES:
      Proportions of injuries by diagnosis, body site, and mechanisms. RESULTS: The
      common injuries noted were contusions and head injuries, fractures of the upper
      extremities, and contusions to both lower and upper extremities. Hospitalizations
      after injury were rare (1.0%). Body contacts, intentional or incidental,
      accounted for 63% of all injuries. The actual ringette (rubber ring) was not
      involved in any injury. CONCLUSIONS: Even though all types of contact are
      forbidden in ringette, our research showed that in minor leagues, a significant
      proportion of the injuries were caused by body contact. As with regular ice
      hockey, enforcing policies regarding contacts, use of proper equipment, good
      maintenance (ice conditions should be checked regularly), and proper skill
      training should help diminish these types of injuries.

PMID- 24326928
TI  - An exploratory study of respiratory muscle endurance training in high lesion
      level paraplegic handbike athletes.
AB  - OBJECTIVE: To investigate the impact of respiratory muscle endurance training
      (RMET) on lung function and exercise performance in athletes with high lesion
      level paraplegia. DESIGN: This was a case-control intervention study. SETTING:
      Sport and exercise science laboratories and bike path. PARTICIPANTS: Twelve
      competitive handbike athletes with high lesion level paraplegia matched by lesion
      and fitness level in training (T) group (7) and control (C) group (5).
      INTERVENTIONS: The T group performed 20 RMET training sessions over a 4-week
      period using a SpiroTiger. Each session lasted for 30 minutes. The C group did
      not perform any RMET. MAIN OUTCOME MEASURES: Resting lung function, respiratory
      muscle endurance, and exercise performance (arm cranking maximal incremental test
      and simulated handbike time trial). RESULTS: Resting lung function was not
      different between groups and did not change with the intervention. After RMET,
      the respiratory muscle endurance was significantly increased by 27% in the T
      group but did not alter in the C group. Final minute ventilation was increased
      from 89 +/- 20 L/min to 112 +/- 20 L/min after RMET in the T group and the
      sensation of dyspnea decreased (P < 0.05). Peak oxygen consumption, peak
      mechanical power output, and handbike time trial performance were not different
      between groups and did not change with the RMET intervention. CONCLUSIONS: A
      short-term RMET intervention in handbike athletes with high lesion level
      paraplegia improved respiratory muscle endurance but had little impact on overall
      exercise performance.

PMID- 24326929
TI  - Bone loss over 1 year of training and competition in female cyclists.
AB  - OBJECTIVE: To observe changes in hip, spine, and tibia bone characteristics in
      female cyclists over the course of 1 year of training. DESIGN: Prospective
      observational study. SETTING: Laboratory. PARTICIPANTS: Female cyclists (n = 14)
      aged 26-41 years with at least 1 year of competition history and intent to
      compete in 10 or more races in the coming year. ASSESSMENT OF RISK FACTORS: Women
      who train and compete in road cycling as their primary sport. MAIN OUTCOME
      MEASURES: Total body fat-free and fat mass and lumbar spine and proximal femur
      areal bone mineral density (aBMD) and bone mineral content (BMC) assessments by
      dual-energy x-ray absorptiometry. Volumetric BMD and BMC of the tibia were
      measured by peripheral quantitative computed tomography at sites corresponding to
      4%, 38%, 66%, and 96% of tibia length. Time points were baseline and after 12
      months of training and competition. RESULTS: Weight and body composition did not
      change significantly over 12 months. Total hip aBMD and BMC decreased by -1.4% +/
      1.9% and -2.1% +/- 2.3% (P < 0.02) and subtrochanter aBMD and BMC decreased by 
      2.1% +/- 2.0% and -3.3% +/- 3.7% (P < 0.01). There was a significant decrease in
      lumbar spine BMC (-1.1% +/- 1.9%; P = 0.03). There were no significant bone
      changes in the tibia (P > 0.11). CONCLUSIONS: Bone loss in female cyclists was
      site specific and similar in magnitude to losses previously reported in male
      cyclists. Research is needed to understand the mechanisms for bone loss in
      cyclists.

PMID- 24326930
TI  - Analyses of Helsinki 2012 European Athletics Championships injury and illness
      surveillance to discuss elite athletes risk factors.
AB  - OBJECTIVE: To further analyze newly incurred injuries and illnesses (I&Is) during
      Athletics International Championships to discuss risk factors. DESIGN:
      Prospective recording of newly occurred injuries and illnesses. SETTING: The 2012
      European Athletics (EA) Championships in Helsinki, Finland. PARTICIPANTS:
      National team and local organizing committee physicians and physiotherapists and
      1342 registered athletes. MAIN OUTCOME MEASURES: Incidence and characteristics of
      new injuries and illnesses. RESULTS: Ninety-three percent of athletes were
      covered by medical teams, with a response rate of 91%. One hundred thirty-three
      injuries were reported (incidence of 98.4 injuries per 1000 registered athletes).
      Sixty-two injuries (47%) resulted in time loss from sport. The most common
      diagnosis was hamstring strain (11.4% of injuries and 21% of time-loss injuries).
      Injury risk was higher in males and increased with age. The highest incidences of
      injuries were found in combined events and middle- and long-distance events.
      Twenty-seven illnesses were reported (4.0 illnesses per 1000 athlete days). The
      most common diagnoses were upper respiratory tract infection (33.3%) and
      gastroenteritis/diarrhea (25.9%). CONCLUSIONS: During outdoor EA Championships,
      injury and illness incidences were slightly lower and injury characteristics were
      comparable with those during outdoor World Athletics Championships. During elite
      athletics Championships, gender (male), age (older than 30 years), finals, and
      some events (combined events and middle- and long-distance races) seem to be
      injury risk factors. Illness risk factors remain unclear. As in previous
      recommendations, preventive interventions should focus on overuse injuries,
      hamstring strains, and adequate rehabilitation of previous injuries, decreasing
      risk of infectious diseases transmission, appropriate event scheduling, sports
      clothes, and heat acclimatization.

PMID- 24326931
TI  - The role of magnetic resonance imaging in a Division I university sports medicine
      program.
AB  - OBJECTIVE: To prospectively document musculoskeletal magnetic resonance imaging
      (MRI) use and how it affects diagnosis, playing status, and treatment of Division
      I university athletes. We hypothesized that MRI often has little or no effect on
      the diagnosis or treatment plan. DESIGN: Cross-sectional study. SETTING: Division
      I university sports medicine program. PATIENTS: Division I university varsity
      athletes. INTERVENTIONS: Data were collected of musculoskeletal MRI use in
      varsity student athletes for 2 full academic years from 2010 to 2012 at a
      National Collegiate Athletic Association Division I institution. MAIN OUTCOME
      MEASURES: Timing of the injury, first physician visit, and MRI and pre- and post
      MRI diagnosis, playing status, and treatment (surgical vs nonsurgical). RESULTS:
      Eighty-six MRIs were obtained during the 2 years studied. Average age was 19.9
      (18-23) years. Forty-five percent of injuries occurred during competition season,
      34% occurred preseason, and 21% occurred postseason. There was a change in
      diagnosis in 13 athletes (15.1%, 1 led to surgery performed after completion of
      the season), and there was a change in participation status in 8 athletes (9.3%,
      5 increased and 3 decreased). Treatment plan changed in 1 athlete (1.2%). No
      athlete required surgery immediately after an MRI that was not already being
      planned. Every athlete treated nonsurgically pre-MRI was able to finish their
      season. CONCLUSIONS: Magnetic resonance imaging was obtained in 14% of athletes
      and did not demonstrate a clear benefit over history, examination, and
      radiographs. Magnetic resonance imaging did change diagnosis in 15% of cases,
      though it did not appreciably change the playing status or treatment plan.

PMID- 24326932
TI  - Body mass index, nutritional knowledge, and eating behaviors in elite student and
      professional ballet dancers.
AB  - OBJECTIVE: It is recognized that there is a high esthetic demand in ballet, and
      this has implications on dancers' body mass index (BMI) and eating behaviors. The
      objective of this study was to examine the association between BMI, eating
      attitudes, and nutritional knowledge of elite student and professional ballet
      dancers. DESIGN: Observational design. SETTING: Institutional. PARTICIPANTS: One
      hundred eighty-nine participants from an elite full-time dance school (M = 53, F
      = 86) and from an elite ballet company (M = 16, F = 25) volunteered for the
      study. There were no exclusion criteria. INTERVENTIONS: Anthropometric data
      (height and mass), General Nutrition Knowledge Questionnaire (GNKQ), and the
      Eating Attitude Test-26 (EAT-26) were collected from each participant. MAIN
      OUTCOME MEASURES: Univariate analysis of variance was used to examine differences
      in gender and group for BMI, GNKQ, and EAT-26. Regression analyses were applied
      to examine interactions between BMI, GNKQ, and EAT-26. RESULTS: Professional
      dancers had significantly greater BMI than student dancers (P < 0.001), and males
      had significantly higher BMI scores than females (P < 0.05). Food knowledge
      increased with age (P < 0.001) with no gender difference. Student dancers had a
      significant interaction between year group and gender because of significantly
      higher EAT-26 scores for females in years 10 and 12. Regression analysis of the
      subcategories (gender and group) reported a number of significant relationships
      between BMI, GNKQ, and EAT-26. CONCLUSIONS: The findings suggest that dancers
      with disordered eating also display lower levels of nutritional knowledge, and
      this may have an impact on BMI. Female students' eating attitudes and BMI should
      especially be monitored during periods of adolescent development.

PMID- 24326933
TI  - Head impact exposure in youth football: elementary school ages 7-8 years and the
      effect of returning players.
AB  - OBJECTIVE: To provide data describing the head impact exposure of 7- to 8-year
      old football players. DESIGN: Head impact data were collected from 19 players
      over the course of 2 seasons using helmet-mounted accelerometer arrays. SETTING:
      Data were collected from 2 youth football teams in Blacksburg, VA, spanning 2
      seasons. PARTICIPANTS: A total of 19 youth football players aged 7-8 years.
      INDEPENDENT VARIABLES: Type of session (practice or game) and the player's
      experience. MAIN OUTCOME MEASURES: Head impact frequency, acceleration magnitude,
      and impact location for games, practices, and the season as a whole were
      measured. RESULTS: The average instrumented player sustained 9 +/- 6 impacts per
      practice, 11 +/- 11 impacts per game, and 161 +/- 111 impacts per season. The
      average instrumented player had a median impact of 16 +/- 2 g and 686 +/- 169
      rad/s and a 95th percentile impact of 38 +/- 13 g and 2052 +/- 664 rad/s
      throughout a season. Impacts of 40 g or greater tended to occur more frequently
      in practices than in games, and practices had a significantly higher 95th
      percentile impact magnitude than games (P = 0.023). Returning players had
      significantly more impacts than first time players (P = 0.007). CONCLUSIONS:
      These data are a further step toward developing effective strategies to reduce
      the incidence of concussion in youth football and have applications toward youth
      specific football helmet designs.

PMID- 24326934
TI  - Low paternal dietary folate alters the mouse sperm epigenome and is associated
      with negative pregnancy outcomes.
AB  - Epidemiological studies suggest that a father's diet can influence offspring
      health. A proposed mechanism for paternal transmission of environmental
      information is via the sperm epigenome. The epigenome includes heritable
      information such as DNA methylation. We hypothesize that the dietary supply of
      methyl donors will alter epigenetic reprogramming in sperm. Here we feed male
      mice either a folate-deficient or folate-sufficient diet throughout life.
      Paternal folate deficiency is associated with increased birth defects in the
      offspring, which include craniofacial and musculoskeletal malformations. Genome
      wide DNA methylation analysis and the subsequent functional analysis identify
      differential methylation in sperm of genes implicated in development, chronic
      diseases such as cancer, diabetes, autism and schizophrenia. While >300 genes are
      differentially expressed in offspring placenta, only two correspond to genes with
      differential methylation in sperm. This model suggests epigenetic transmission
      may involve sperm histone H3 methylation or DNA methylation and that adequate
      paternal dietary folate is essential for offspring health. 

PMID- 24326936
TI  - Association of body mass index and long-term outcomes in older patients with non
      ST-segment-elevation myocardial infarction: results from the CRUSADE Registry.
AB  - BACKGROUND: Prior studies have found that obese patients have paradoxically lower
      in-hospital mortality after non-ST-segment-elevation myocardial infarction than
      their normal-weight counterparts, yet whether these associations persist long
      term is unknown. METHODS AND RESULTS: We linked detailed clinical data for
      patients with non-ST-segment-elevation myocardial infarction aged >=65 years in
      the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse
      Outcomes With Early Implementation of the American College of Cardiology/American
      Heart Association Guidelines (CRUSADE) Registry to Medicare claims data to obtain
      longitudinal outcomes. Using height and weight measured on admission, patients
      were categorized into 6 body mass index (BMI [kilograms per meter squared])
      groups. Multivariable Cox proportional hazards models were used to estimate the
      association between BMI and (1) all-cause mortality, (2) all-cause readmission,
      (3) cardiovascular readmission, and (4) noncardiovascular readmission for 3 years
      after hospital discharge. Among older patients with non-ST-segment-elevation
      myocardial infarction (n=34,465), 36.3% were overweight and 27.7% were obese.
      Obese patients were younger and more likely to have hypertension, diabetes
      mellitus, and dyslipidemia than normal or underweight patients. Relative to
      normal-weight patients, long-term mortality was lower for patients classified as
      overweight (BMI, 25.0-29.9), obese class I (BMI, 30.0-34.9), and obese class II
      (BMI, 35.0-39.9), but not obese class III (BMI >=40.0). In contrast, 3-year all
      cause and cardiovascular readmission were similar across BMI categories. Relative
      to normal-weight patients, noncardiovascular readmissions were similar for obese
      class I but higher for obese class II and obese class III. CONCLUSIONS: All-cause
      long-term mortality was generally lower for overweight and obese older patients
      after non-ST-segment-elevation myocardial infarction relative to those with
      normal weight. Longitudinal readmissions were similar or higher with increasing
      BMI.

PMID- 24326935
TI  - Association of body mass index and mortality after acute ischemic stroke.
AB  - BACKGROUND: The prevalence of severe obesity is rising in the United States.
      Although mild to moderately elevated body mass index (BMI) is associated with
      reduced mortality after acute ischemic stroke, less is known about severe
      obesity. METHODS AND RESULTS: Patients with acute ischemic stroke (n=1791) >=45
      years were identified from the biethnic population-based Brain Attack
      Surveillance in Corpus Christi (BASIC) study from June 1, 2005, to December 31,
      2010. Median follow-up was 660 days. BMI was abstracted from the medical record.
      Survival was estimated by BMI category (underweight, normal weight, overweight,
      class 1 obesity, class 2 obesity, and severe obesity) using Kaplan-Meier methods.
      Hazard ratios for the relationship between BMI modeled continuously and mortality
      were estimated from Cox regression models after adjustment for patient factors.
      The median BMI was 27.1 kg/m(2) (interquartile range, 23.7-31.2 kg/m(2)), and 56%
      were Mexican American. A total of 625 patients (35%) died during the study
      period. Persons with higher baseline BMI had longer survival in unadjusted
      analysis (P<0.01). After adjustment for demographics, stroke severity, and stroke
      and mortality risk factors, the relationship between BMI and mortality was U
      shaped. The lowest mortality risk was observed among patients with an approximate
      BMI of 35 kg/m(2), whereas those with lower or higher BMI had higher mortality
      risk. CONCLUSIONS: Severe obesity is associated with increased poststroke
      mortality in middle-aged and older adults. Stroke patients with class 2 obesity
      had the lowest mortality risk. More research is needed to determine weight
      management goals among stroke survivors.

PMID- 24326937
TI  - Comorbidity influenced health-related quality of life of 390 patients with
      idiopathic scoliosis at long-term follow-up.
AB  - BACKGROUND: Comorbidity is common in patients with low back pain and is
      associated with a poorer prognosis, but this has not been evaluated in patients
      with idiopathic scoliosis. AIM: To evaluate comorbidity and health-related
      quality of life in scoliosis patients. DESIGN: Cross-sectional study. SETTING:
      Outpatient clinic. POPULATION: Four hundred and ninety-six patients treated with
      Boston brace for idiopathic scoliosis were invited for long-term follow-up. 390
      patients (361 women and 29 men) responded. Mean age was 39.2 (+/-4.6) years; mean
      follow-up time 23.4 (+/-4.3) years after brace weaning. Twenty-eight patients had
      been operated, 27 of these had long-term follow-up. METHODS: Radiographs at
      baseline, brace weaning, and follow-up. Validated questionnaires for evaluation
      of health-related quality of life including Scoliosis Research Society (SRS-22)
      and EuroQol (EQ-5D) were applied at follow-up. RESULTS: 122 (31%) patients
      reported that they had at least one comorbid condition at long-term follow-up.
      The most common diseases were: asthma (N.=14); migraine (N.=13); lower extremity
      disorders (N.=10); anxiety/depression (N.=9); allergy (N.=9); cardiovascular
      disease (N.=8); lumbar disc herniation (N.=8); neck pain or injury (N.=8); and
      widespread pain (N.=8). Age at bracing and at menarche, compliance, curve sizes,
      and the number of patients operated, were not different in those who did have and
      those who did not have comorbidity. Sixty-one percent with comorbidity versus 78%
      without (P<0.001) had excellent or good back function, and 57% versus 86% worked
      full-time. Those with comorbidity had significantly (P<0.001) worse SRS-22 scores
      for pain, function, self-image, and mental health, but not for satisfaction with
      bracing. Mean EQ-5D was 0.74 with comorbidity and 0.85 (normal for age and
      gender) without (P<0.001). Curve size was not significantly associated with any
      health-related quality of life outcome, while operated patients had worse SRS-22
      scores for self-image and function (P=0.03). CONCLUSION: About one-third of
      middle aged patients with idiopathic scoliosis reported to have at least one
      comorbid condition. Results indicate that comorbidity influences health related
      quality of life. CLINICAL REHABILITATION IMPACT: Comorbidity should be considered
      when interpreting scores of health-related quality of life in patients with
      idiopathic scoliosis.

PMID- 24326946
TI  - Who is responsible for publishing the results of old trials?

PMID- 24326945
TI  - Pharmacological and pharmacokinetic studies with vitamin D-loaded nanoemulsions
      in asthma model.
AB  - Vitamin D (VD) was studied for its anti-inflammatory activities with prepared VD
      loaded nanoemulsions (VDNM) in ovalbumin-induced asthmatic mice in this paper. In
      this study, we prepared VDNM for the delivery of VD from the established
      composition of solid self-emulsifying drug delivery systems (sSEDDS) by spray
      drying technique and evaluated its bioavailability (BA) and anti-inflammatory
      activities in experimental allergic asthma. After the mice were treated orally
      with VD or VDNM, the plasma 25(OH) D levels, polymorphonuclear cells, tumor
      necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), total
      antioxidant activity, and C3 and C4 complement protein levels were studied,
      respectively. Treatment with VDNM reduced MPO activity, oxidative stress, C3
      protein level, O2(-) level as well as the production of IL-1beta and TNF-alpha.
      Pharmacokinetic studies showed that a significant increase in the maximum
      concentration (Cmax) and AUC0->24 h were observed in VDNM group when compared
      with VD group (P < 0.01). The result revealed that VDNM led to an improvement in
      oral BA of VD in a murine ovalbumin-induced asthma model. These data provided an
      important proof that VDNM might be a new potential therapy for the management of
      asthma in humans.

PMID- 24326947
TI  - Impact of a financial risk-sharing scheme on budget-impact estimations: a game
      theoretic approach.
AB  - BACKGROUND: As part of the process of updating the National List of Health
      Services in Israel, health plans (the 'payers') and manufacturers each provide
      estimates on the expected number of patients that will utilize a new drug.
      Currently, payers face major financial consequences when actual utilization is
      higher than the allocated budget. We suggest a risk-sharing model between the two
      stakeholders; if the actual number of patients exceeds the manufacturer's
      prediction, the manufacturer will reimburse the payers by a rebate rate of alpha
      from the deficit. In case of under-utilization, payers will refund the government
      at a rate of gamma from the surplus budget. Our study objective was to identify
      the optimal early estimations of both 'players' prior to and after implementation
      of the risk-sharing scheme. METHODS: Using a game-theoretic approach, in which
      both players' statements are considered simultaneously, we examined the impact of
      risk-sharing within a given range of rebate proportions, on players' early budget
      estimations. RESULTS: When increasing manufacturer's rebate alpha to be over 50
      %, then manufacturers will announce a larger number, and health plans will
      announce a lower number of patients than they would without risk sharing, thus
      substantially decreasing the gap between their estimates. Increasing gamma
      changes players' estimates only slightly. CONCLUSION: In reaction to applying a
      substantial risk-sharing rebate alpha on the manufacturer, both players are
      expected to adjust their budget estimates toward an optimal equilibrium.
      Increasing alpha is a better vehicle for reaching the desired equilibrium rather
      than increasing gamma, as the manufacturer's rebate alpha substantially
      influences both players, whereas gamma has little effect on the players behavior.

PMID- 24326948
TI  - Direct modeling of the electrochemistry in the three-phase boundary of solid
      oxide fuel cell anodes by density functional theory: a critical overview.
AB  - The first principles modeling of electrochemical reactions has proven useful for
      the development of efficient, durable and low cost solid oxide full cells
      (SOFCs). In this account we focus on recent advances in modeling of structural,
      electronic and catalytic properties of the SOFC anodes based on density
      functional theory (DFT) first principle calculations. As a starting point, we
      highlight that the adequate analysis of cell electrochemistry generally requires
      modeling of chemical reactions at the metal/oxide interface rather than on
      individual metal or oxide surfaces. The atomic models of Ni/YSZ and Ni/CeO2
      interfaces, required for DFT simulations of reactions on SOFC anodes are
      discussed next, together with the analysis of the electronic structure of these
      interfaces. Then we proceed to DFT-based findings on charge transfer mechanisms
      during redox reactions on these two anodes. We provide a comparison of the
      electronic properties of Ni/YSZ and Ni/CeO2 interfaces and present an
      interpretation of their different chemical performances. Subsequently we discuss
      the computed energy pathways of fuel oxidation mechanisms, obtained by various
      groups to date. We also discuss the results of DFT studies combined with
      microkinetic modeling as well as the results of kinetic Monte Carlo simulations.
      In conclusion we summarize the key findings of DFT modeling of metal/oxide
      interfaces to date and highlight possible directions in the future modeling of
      SOFC anodes. 

PMID- 24326949
TI  - Emergence of scaling in human-interest dynamics.
AB  - Human behaviors are often driven by human interests. Despite intense recent
      efforts in exploring the dynamics of human behaviors, little is known about human
      interest dynamics, partly due to the extreme difficulty in accessing the human
      mind from observations. However, the availability of large-scale data, such as
      those from e-commerce and smart-phone communications, makes it possible to probe
      into and quantify the dynamics of human interest. Using three prototypical "Big
      Data" sets, we investigate the scaling behaviors associated with human-interest
      dynamics. In particular, from the data sets we uncover fat-tailed (possibly power
      law) distributions associated with the three basic quantities: (1) the length of
      continuous interest, (2) the return time of visiting certain interest, and (3)
      interest ranking and transition. We argue that there are three basic ingredients
      underlying human-interest dynamics: preferential return to previously visited
      interests, inertial effect, and exploration of new interests. We develop a biased
      random-walk model, incorporating the three ingredients, to account for the
      observed fat-tailed distributions. Our study represents the first attempt to
      understand the dynamical processes underlying human interest, which has
      significant applications in science and engineering, commerce, as well as
      defense, in terms of specific tasks such as recommendation and human-behavior
      prediction. 

PMID- 24326950
TI  - Factors affecting quality of life in early childhood in patients with congenital
      hydrocephalus.
AB  - BACKGROUND: Predicting the outcome of congenital hydrocephalus in early infancy
      and childhood is difficult. Various consequences of hydrocephalus like
      ophthalmic, audiometric, musculoskeletal, and the developmental abnormalities
      play a complex role. We analyzed the quality of life of these patients in early
      life. METHODS: A prospective multispecialty assessment of the patients with
      congenital hydrocephalus, who had undergone ventriculoperitoneal shunt in the
      Pediatric Surgery unit of a tertiary care hospital, was carried out and analyzed.
      RESULTS: There were 24 boys and 6 girls. Eighty-three percent were operated
      before the age of 3 months. Mean age at follow up was 6 years (3-9 years). Shunt
      complications were seen in 53% (16) of the patients, out of which 68.75% had
      shunt blocks. In 70% (21) of the patients, the ventricle to hemisphere ratio
      (VHR) was between 51 and 70%, 20% (6) had a VHR of more than 70% and only 3
      patients had a VHR between 40-50%. Audiological and ophthalmic problems were seen
      in 20 and 66% of the children, respectively. Musculoskeletal abnormalities were
      present in 36% of the patients. Developmental profile showed 44% being normal,
      30% retarded, and 26% were borderline cases. The schooling had started in 56.6%,
      out of which only one child went to a special school. CONCLUSIONS: A multitude of
      problems associated with congenital hydrocephalus should be diligently diagnosed,
      aggressively followed and intervened with in the early years of life. Preschool
      management well before the peer interaction should optimize the social
      integration and improve the quality of life in these patients.

PMID- 24326951
TI  - Depression in parents of children with leukemia in southern China accompanied by
      the prevalence of type D personality.
AB  - PURPOSE: The aims of this study were to assess depression and type D personality
      in parents of children with leukemia in southern China and to investigate the
      associations between parents' depression and type D personality, social support,
      coping style, and demographic characteristics. METHODS: Parents (n=231) of
      children with leukemia (study group) and parents (n=261) of children with acute
      respiratory/digestive infections (control group) were recruited from five
      hospitals in southern China. Children's clinical characteristics and parents'
      demographic characteristics, depression, type D personality, coping styles, and
      social support were collected with self-report questionnaires. RESULTS: Parents
      of children with leukemia, especially mothers, reported higher levels of
      depression accompanied by a higher prevalence of type D personality, more
      negative coping styles, and less subjective social support, but received more
      objective social support than controls (P<0.05). The depression in parents in the
      study group was positively correlated with type D personality and negative coping
      style, but negatively correlated with social support and positive coping styles
      (P<0.05). Multivariate logistic regression analyses showed that type D
      personality (OR=5.64, P<0.001), lower social support (OR=2.38, P=0.020), and less
      positive coping (OR=3.32, P=0.003) were independently associated with depression
      in parents of children with leukemia. As for demographic characteristics, female,
      lower education level, unemployed, and paying medical expenses at one's own
      expenses were independent predictors of depression in parents of children with
      leukemia. CONCLUSION: Depression and type D personality were remarkably prevalent
      in parents of children with leukemia in southern China. Type D personality and
      multiple social factors were associated with depression in parents of children
      with leukemia.

PMID- 24326952
TI  - Upper extremity morbidity after radial forearm flap harvest: a prospective study.
AB  - OBJECTIVE: To determine the effect of radial forearm free (RFF) flap harvest on
      patient-reported postoperative upper extremity disability. METHODS: Patients
      undergoing RFF flap reconstruction following resection of head and neck cancer
      were recruited and matched with similar patients undergoing non-RFF
      reconstruction. All subjects completed the Disability of the Arm, Shoulder, and
      Hand (DASH) questionnaire preoperatively and at least 1 year postoperatively.
      RESULTS: Postoperative DASH scores were significantly higher (more severe
      disability) in patients undergoing RFF flap reconstruction (6.93 +/- 5.54; n =
      52) compared with those undergoing non-RFF flap surgeries (2.95 +/- 4.42; n =
      52). Preoperative DASH score, flap size, patient age and tumour stage were
      significantly correlated with postoperative DASH score. CONCLUSION: Excluding the
      effect of neck dissection, RFF flap reconstruction has a significant deleterious
      effect on upper extremity function.

PMID- 24326953
TI  - Postoperative complications after closed calcaneus fracture treated by open
      reduction and internal fixation: a review.
AB  - OBJECTIVE: To review postoperative complications reported after closed calcaneus
      fracture treated by open reduction and internal fixation (ORIF). METHODS:
      Postoperative complications reported in the literature between 1995 and 2012 were
      identified. Papers were retrieved from publicly available databases and included
      in this study if they met the following criteria: clinical research of cases of
      closed calcaneus fracture treated by ORIF; >=10 cases; detailed information about
      complications, treatment and follow up. RESULTS: Twenty-one clinical reports were
      analysed (2046 cases). Reported complications (and incidence rates) were:
      infection and skin flap necrosis (13.6%); neurovascular injury (2.8%); post
      traumatic arthritis (1.2%); malreduction/implant problems (0.8%); nonunion
      (0.1%). CONCLUSIONS: Postoperative complications after closed calcaneus fracture
      are common clinical problems that cannot always be avoided. They can even be life
      altering, due to the requirement for long-term treatment or amputation and their
      economic impact on the patient. Complications should be diagnosed and treated
      promptly, to achieve satisfactory outcomes. Nonsurgical treatment (e.g. local
      wound care, drugs or physical therapy) can be attempted. If such measures fail,
      surgical treatment (e.g. debridement, skin flap transplantation, implant removal,
      re-opening of the reduction and internal fixation or subtalar joint arthrodesis)
      should be considered.

PMID- 24326954
TI  - Mechanism of temozolomide-induced antitumour effects on glioma cells.
AB  - OBJECTIVE: To investigate the mechanisms of action of the tumoricidal effects of
      temozolomide against the human glioma cell line U251 in vitro, and to provide
      preclinical proof-of-concept studies of the effects of temozolomide-containing
      regimens. METHODS: U251 cells were exposed to 100 umol/l temozolomide.
      Morphological alterations were monitored by light microscopy. Cell viability was
      measured using the 3 -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. Cell cycle analysis and the rate of apoptosis were determined using
      flow cytometry and the number of acidic vesicular organelles stained with
      acridine orange were analysed by fluorescence microscopy. The scratch recovery
      test was used to measure cell migration. RESULTS: U251 cells that were treated
      with temozolomide displayed morphological alterations indicative of a rounder
      shape and impaired cellular adhesion to the cell culture plate compared with
      control U251 cells. Temozolomide reduced cell viability as measured by the MTT
      assay, caused cell cycle arrest in the gap 2/mitosis phase, inhibited cell
      migration and promoted autophagy in U251 cells. CONCLUSION: Temozolomide induced
      autophagic, but not apoptotic processes, in U251 cells and thus reduced their
      viability and migration.

PMID- 24326957
TI  - Wolf-Hirschhorn syndrome: a historical note and comment on an older adult.

PMID- 24326955
TI  - Cellular therapy in bone-tendon interface regeneration.
AB  - The intrasynovial bone-tendon interface is a gradual transition from soft tissue
      to bone, with two intervening zones of uncalcified and calcified fibrocartilage.
      Following injury, the native anatomy is not restored, resulting in inferior
      mechanical properties and an increased risk of re-injury. Recent in vivo studies
      provide evidence of improved healing when surgical repair of the bone-tendon
      interface is augmented with cells capable of undergoing chondrogenesis. In
      particular, cellular therapy in bone-tendon healing can promote fibrocartilage
      formation and associated improvements in mechanical properties. Despite these
      promising results in animal models, cellular therapy in human patients remains
      largely unexplored. This review highlights the development and structure-function
      relationship of normal bone-tendon insertions. The natural healing response to
      injury is discussed, with subsequent review of recent research on cellular
      approaches for improved healing. Finally, opportunities for translating in vivo
      findings into clinical practice are identified. 

PMID- 24326956
TI  - Non-synaptic roles of acetylcholinesterase and agrin.
AB  - Proteins in living organisms have names that are usually derived from their
      function in the biochemical system their discoverer was investigating. Typical
      examples are acetylcholinesterase and agrin; however, for both of these, various
      other functions that are not related to the cholinergic system have been
      revealed. Our investigations have been focused on the alternative roles of
      acetylcholinesterase and agrin in the processes of muscle development and
      regeneration. Previously, we described a role for agrin in the development of
      excitability in muscle contraction. In this study, we report the effects of agrin
      on secretion of interleukin 6 in developing human muscle. At the myoblast stage,
      agrin increases interleukin 6 secretion. This effect seems to be general as it
      was observed in all of the cell models analysed (human, mouse, cell lines). After
      fusion of myoblasts into myotubes, the effects of agrin are no longer evident,
      although agrin has further effects at the innervation stage, at least in in vitro
      innervated human muscle. These effects of agrin are another demonstration of its
      non-synaptic roles that are apparently developmental-stage specific. Our data
      support the view that acetylcholinesterase and agrin participate in various
      processes during development of skeletal muscle. 

PMID- 24326958
TI  - The first report of nephrocalcinosis in a patient with a 16q23.1-16q23.3
      deletion, global developmental delay, trigonocephaly, and portocaval shunt.

PMID- 24326959
TI  - Chitayat-Hall syndrome: extending the clinical phenotype.

PMID- 24326960
TI  - GAPO syndrome with deafness: new feature or incidental finding?

PMID- 24326961
TI  - Syndrome of megalencephaly, mega corpus callosum, and complete lack of motor
      development: exploring the phenotype.

PMID- 24326962
TI  - A patient with hyperphalangism: the milder phenotype of Catel-Manzke syndrome.

PMID- 24326963
TI  - An infant with trisomy 15 mosaicism.

PMID- 24326965
TI  - Possible number systems.
AB  - Number systems-such as the natural numbers, integers, rationals, reals, or
      complex numbers-play a foundational role in mathematics, but these systems can
      present difficulties for students. In the studies reported here, we probed the
      boundaries of people's concept of a number system by asking them whether "number
      lines" of varying shapes qualify as possible number systems. In Experiment 1,
      participants rated each of a set of number lines as a possible number system,
      where the number lines differed in their structures (a single straight line, a
      step-shaped line, a double line, or two branching structures) and in their
      boundedness (unbounded, bounded below, bounded above, bounded above and below, or
      circular). Participants also rated each of a group of mathematical properties
      (e.g., associativity) for its importance to number systems. Relational
      properties, such as associativity, predicted whether participants believed that
      particular forms were number systems, as did the forms' ability to support
      arithmetic operations, such as addition. In Experiment 2, we asked participants
      to produce properties that were important for number systems. Relational,
      operation, and use-based properties from this set again predicted ratings of
      whether the number lines were possible number systems. In Experiment 3, we found
      similar results when the number lines indicated the positions of the individual
      numbers. The results suggest that people believe that number systems should be
      well-behaved with respect to basic arithmetic operations, and that they reject
      systems for which these operations produce ambiguous answers. People care much
      less about whether the systems have particular numbers (e.g., 0) or sets of
      numbers (e.g., the positives). 

PMID- 24326964
TI  - The antinociceptive effect of 4-substituted derivatives of 5-(4-chlorophenyl)-2
      (morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in mice.
AB  - The aim of the present experiments was to examine the antinociceptive activity of
      4-substituted derivatives of 5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4
      dihydro-3H-1,2,4-triazole-3-thione in mice. The compounds were synthesized using
      the so-called Mannich reaction and their structures were confirmed using IR and
      1H-NMR spectra. The antinociceptive activity was investigated in two behavioral
      tests: the hot plate test and the writhing test. For preliminary estimation of
      other behavioral effects, the locomotor activity of mice, the motor coordination
      in the rota-rod test, and the myorelaxation in the chimney test were also
      studied. The changes in body temperature of animals were also recorded. We
      demonstrated that all examined compounds produced antinociceptive effect, both in
      the hot plate test and in the writhing test, without impact on the motor
      coordination and myorelaxation of animals. The pharmacological effect of all
      drugs has been developed within 60 min after administration of drugs; and in two
      cases (T-103 and T-104), it has been a short-lasting effect (up to 90 min). Two
      compounds (T-100 and T-102) also inhibited the locomotor activity of animals. T
      104 induced the changes in body temperature of mice. Generally, we demonstrated
      that combination of two different heterocyclic systems (morpholine and 1,2,4
      triazole) might be beneficial for reduction of nociception. 

PMID- 24326967
TI  - Surgically induced astigmatism following glaucoma surgery in Egyptian patients.
AB  - PURPOSE: The altered visual function induced by changes in corneal curvature
      following filtration surgery is distressing to patients. The aim of this study
      was to evaluate surgically induced astigmatism following trabeculectomy in
      comparison with deep sclerectomy. METHODS: In a prospective interventional
      comparative study, patients with primary open-angle glaucoma were randomly
      allocated to either group A or B; deep sclerectomy with mitomycin C 0.2 mg/mL and
      trabeculectomy with mitomycin C 0.2 mg/mL, respectively. Keratometry was
      performed using Topcon KR-7000P autokerato-refractometer preoperatively and at 6
      months postoperatively. Vector analysis was used to analyze the surgically
      induced astigmatism. RESULTS: Sixty eyes of 45 patients in group A, and 60 eyes
      of 42 patients in group B were enrolled for vector analysis. The mean
      preoperative astigmatic vector power was -0.49+/-1.65 D and +0.47+/-2.18 D in
      groups A and B, respectively. The mean postoperative astigmatic vector power was 
      1.14+/-1.55 D in group A and -0.35+/-1.8 D in group B. The mean change in
      astigmatic vector powers was -0.67+/-1.63 D in group A and -0.82+/-2.0 D in group
      B. When compared with preoperative data in either group, the differences were
      significant, P=0.001 & 0.007 in groups A and B respectively, whereas the
      postoperative difference between either group was insignificant (P=0.723). A
      total of 40% of corneas got flatter in group B compared with 25% in group A,
      P=0.057. CONCLUSIONS: Both trabeculectomy and deep sclerectomy induced
      considerable postoperative astigmatism. A longer follow-up period is recommended
      to study the different patterns of astigmatism in either procedure.

PMID- 24326966
TI  - Beauty is in the ease of the beholding: a neurophysiological test of the
      averageness theory of facial attractiveness.
AB  - Hundreds of studies have shown that people prefer attractive over unattractive
      faces. But what is an attractive face, and why is it preferred? Averageness
      theory claims that faces are perceived as being attractive when their facial
      configuration approximates the mathematical average facial configuration of the
      population. Conversely, faces that deviate from this average configuration are
      perceived as being unattractive. The theory predicts that both attractive and
      mathematically averaged faces should be processed more fluently than unattractive
      faces, whereas the averaged faces should be processed marginally more fluently
      than the attractive faces. We compared neurocognitive and behavioral responses to
      attractive, unattractive, and averaged human faces to test these predictions. We
      recorded event-related potentials (ERPs) and reaction times (RTs) from 48 adults
      while they discriminated between human and chimpanzee faces. The participants
      categorized averaged and high-attractive faces as being "human" faster than low
      attractive faces. The posterior N170 (150-225 ms) face-evoked ERP component was
      smaller in response to high-attractive and averaged faces than to low-attractive
      faces. Single-trial electroencephalographic analysis indicated that this reduced
      ERP response arose from the engagement of fewer neural resources, and not from a
      change in the temporal consistency of how those resources were engaged. These
      findings provide novel evidence that faces are perceived as being attractive when
      they approximate a facial configuration close to the population average, and they
      suggest that processing fluency underlies preferences for attractive faces. 

PMID- 24326968
TI  - Evaluation of Risk Factors for Glaucoma Drainage Device-related Erosions: A
      Retrospective Case-Control Study.
AB  - PURPOSE: To identify risk factors for glaucoma drainage device (GDD) erosions.
      PATIENTS AND METHODS: In a retrospective comparative case series, medical records
      of 1013 patients who underwent GDD surgery performed by 5 surgeons between 2006
      and 2011 were reviewed. The outcome measures assessed included age, race, sex,
      contact lens wear, seasonal allergies, medical comorbidities, glaucoma diagnosis,
      preoperative oral and topical medications, type and number of preoperative
      surgeries and lasers, concomitant surgeries, tube type and position, patch graft
      material, and intraoperative use of Avastin, mitomycin-C, or Triescence. The
      association of variables with erosion status was evaluated using the Fisher exact
      test for categorical variables and the exact Wilcoxon rank-sum test for
      continuous variables. RESULTS: Charts were included from 339 eyes that had
      complete data sets and at least 6 months of follow-up. Twenty-eight eyes (8.3%)
      developed conjunctival erosions. The median follow-up time was 2.03 years for the
      erosion group and 1.71 years for nonerosion group. Erosion was only associated
      with the presence of concomitant surgical procedures at the time of GDD
      implantation (35.7% erosion group vs. 17.4% nonerosion group, P=0.02, OR=2.64).
      The majority of concomitant surgeries were composed of pars plana vitrectomy
      (35.0%) and cataract surgery (32.0%). Variables that were suggestive of
      association with erosion (P<0.20) included smoking (OR=2.14), pseudoexfoliation
      glaucoma (OR=2.71), and history of dry eye syndrome (OR=2.22). CONCLUSION:
      History of concomitant intraocular surgery with GDD implantation may be a
      potential risk factor for future erosions.

PMID- 24326969
TI  - Structural landscape of the 1 : 1 benzoic acid : isonicotinamide cocrystal.
AB  - The acid-pyridine heterosynthon may be used as a "molecular" module to probe the
      structural landscape of the benzoic acid : isonicotinamide 1 : 1 cocrystal, BA :
      INA. Experimental structures of 1 : 1 cocrystals of fluorobenzoic acids (FBA)
      with isonicotinamide (INA) contain this heterosynthon and correspond to high
      energy structures of 1 : 1 BA : INA.

PMID- 24326970
TI  - Effects of intracisternal tramadol on cerebral and spinal neuronal cells in rat.
AB  - BACKGROUND: The aim was to investigate whether tramadol had toxic effect on
      cerebral neurons and/or spinal cord neurons when it was administered into the
      cerebrospinal fluid. Due to lipid peroxidation (LPO) and myeloperoxidation (MPO)
      levels are not specific predictors of neuronal damage, these biochemical markers
      of tissue damage were evaluated together with the histopathological findings of
      apoptosis. METHODS: Forty eight Wistar rats were anesthetized and the right
      femoral artery was cannulated. Mean arterial pressures, and heart rates, arterial
      carbon dioxide tension, arterial oxygen tension, blood pH were recorded. When the
      free cerebrospinal fluid flow was seen; 0.04 mL normal saline (Group Sham) or
      diluted tramadol in 0.04 mL volume (Group T1, T2, T0.5 and T0.1) was administered
      within 30 seconds from the posterior craniocervical junction of rats. For the
      Control Group, the free cerebrospinal fluid flow was seen but nothing was
      injected in it. After 7 days, following the sacrification of the rats, brain
      tissue, cervical and lumber segments of spinal cord were collected for the
      histopathological and biochemical examination. RESULTS: There was not a
      statistically significant difference among all groups regarding the brain LPO
      levels (P=0.485). The LPO levels of the cervical segment of spinal cord and the
      lumbar segment of spinal cord were also similar (P=0.146, P=0.939, respectively).
      The mean MPO levels of the cervical and the lumbar segments of spinal cord were
      similar among all groups (P=0.693, P=0.377, respectively). There were not any
      statistically significant difference regarding the total number of red neurons of
      the brain tissue and the cervical and lumbar segments of spinal cord among all
      groups (P=0.264, P=0.202, P=0.780, respectively). CONCLUSION: Tramadol had no
      neurotoxic effect on brain and on spinal cord tissue when administered by the
      intracisternal route in cerebrospinal fluid in rats.

PMID- 24326971
TI  - Aminoglycosides for life-threatening infections: a plea for an individualized
      approach using intensive therapeutic drug monitoring.
AB  - Aminoglycosides are potent antibiotics with a renewed interest due to the
      increase in multidrug resistant infections. Their use in life-threatening
      infections - in combination with other antibiotics - has been debated due to the
      lack of clear outcome benefits. However, based on recent pharmacokinetic
      pharmacodynamic studies, conventional dosing may be inefficient in a considerable
      number of patients, which could preclude the efficiency of this potent drug
      class. Toxicity on the other hand remains a concern, with nephrotoxicity as the
      most relevant negative effect in the critically ill. Short term, intensively
      monitored treatment strategies - with monitoring both peak and trough levels -
      may increase efficacy as well as reduce toxicity in the critically ill patient. 

PMID- 24326972
TI  - Mathematical coupling of data between global-end diastolic volume index and
      cardiac index calculated by the PiCCO device: myth or reality?
AB  - BACKGROUND: Aim of the study was to investigate whether cardiac index (CI) and
      global end diastolic volume index (GEDVi) determined from the same thermodilution
      curve are mathematically coupled during the infusion of an inotropic agent in
      critically ill patients. METHODS: Seventeen patients were prospectively studied.
      CI and GEDVi were evaluated in triplicate by the transpulmonary thermodilution
      technique with the PiCCO system before and 20 to 30 minutes after increases in
      dobutamine infusion rate. Mixed linear model was used to determine the within
      subject correlation coefficient between changes in CI and GEDVi induced by
      changes in dobutamine infusion rate. RESULTS: Dobutamine administration
      significantly increased CI by 48+/-35%, whereas the average increase in GEDVi was
      only 8.2+/-12.3% but statistically significant (P<0.0001). The increase of GEDVi
      in response to dobutamine infusion was unexpected given that dobutamine has no
      recognized effect on right and left ventricular dimensions. Intriguingly, we
      observed a significant correlation coefficient, in individual patients, between
      changes in CI and GEDVi (r=0.58, P=0.002). CONCLUSION: Our study provides
      evidence that changes in GEDVi are mathematically coupled to changes in CI during
      dobutamine infusion. Therefore, clinicians using PiCCO device to evaluate GEDVi
      must be aware of the underlying formula to avoid placing undue reliance on
      artifactual correlations due to mathematical coupling.

PMID- 24326973
TI  - Prone position during ECMO: a turn of events?

PMID- 24326974
TI  - Stabilization of a linear nanomechanical oscillator to its thermodynamic limit.
AB  - The rapid development of micro- and nanomechanical oscillators in the past decade
      has led to the emergence of novel devices and sensors that are opening new
      frontiers in both applied and fundamental science. The potential of these devices
      is however affected by their increased sensitivity to external perturbations.
      Here we report a non-perturbative optomechanical stabilization technique and
      apply the method to stabilize a linear nanomechanical beam at its thermodynamic
      limit at room temperature. The reported ability to stabilize a nanomechanical
      oscillator to the thermodynamic limit can be extended to a variety of systems and
      increases the sensitivity range of nanomechanical sensors in both fundamental and
      applied studies. 

PMID- 24326976
TI  - Competition between n -> pi(Ar)* and conventional hydrogen bonding (N-H...N)
      interactions: an ab initio study of the complexes of 7-azaindole and
      fluorosubstituted pyridines.
AB  - In this work, we have investigated a subtle competition between a very weak n ->
      pi(Ar)* interaction and a very strong hydrogen bond (N-H...N) interaction present
      in the complexes of 7-azaindole with a series of 2,6-substituted fluoropyridines
      and observed how the weak interaction modulates the overall structural motif of
      these complexes in the presence of the strong interaction. We have studied the
      structures and binding energies of these complexes using MP2 as well as
      dispersion-corrected DFT calculations. It has been found that the strength of the
      N-H...N interaction in these complexes decreases with increasing fluorination in
      the fluoropyridine ring while the proximity between the nitrogen atom in 7
      azaindole and the aromatic ring of fluoropyridine increases through n -> pi(Ar)*
      interaction. Comparison of the binding energy values as well as structural
      parameters of these complexes calculated at the B3LYP level with those obtained
      at the MP2, M05-2X, and B97-D levels of theory clearly indicates that the
      dispersion effect is mostly responsible for this attractive n -> pi(Ar)*
      interaction. This conclusion is also supported by localized molecular orbital
      energy decomposition analysis (LMO-EDA). The current investigation is the first
      theoretical study on the n -> pi(Ar)* interaction in the presence of a
      conventional strong hydrogen bonding interaction in the molecular system. Thus
      the present study has great significance for understanding the structures of the
      biomolecules as well as materials, as these interactions are very often present
      there simultaneously.

PMID- 24326977
TI  - Use of an autologous lamellar scleral graft to repair a corneal perforation.
AB  - To report the use of an autologous lamellar scleral graft to close a corneal
      perforation. Our patient was a 55-year-old female who presented with a
      paracentral 2 * 2 mm perforation in the center of a preexisting corneal opacity.
      Because of the unavailability of corneal tissue and the failure to seal the
      perforation with glue, a partial thickness lamellar scleral graft was harvested
      from the inferotemporal quadrant and used to close the corneal defect. There was
      gradual adherence and uptake of the scleral tissue into the surrounding cornea
      along with significant clearing over the next few months. At 9 months, her best
      corrected visual acuity was 20/80 with a stable anterior chamber, focal posterior
      synechiae and early cataract changes. A band of iris tissue was observed within
      the lens substance extending posterolaterally from 1 to 7 o'clock positions. In
      the absence of donor corneal tissue and in selective emergency situations, an
      autologous scleral patch graft can be considered as a viable alternative in the
      treatment of full-thickness corneal perforations. We also report the presence of
      a band of iris tissue within the lens, a finding which has not been previously
      reported.

PMID- 24326979
TI  - Evaluation of VEGF-C and tumor markers in bronchoalveolar lavage fluid for lung
      cancer diagnosis.
AB  - A total of 87 patients were enrolled and bronchoalveolar lavage fluid (BALF)
      samples were obtained from all subjects. A significant difference was found in
      BALF VEGF-C level between patients with squamous cell carcinoma and benign
      diseases (P = 0.043). In addition, the concentration of NSE in BALF form the
      malignant group was significantly higher compared with that of the benign groups
      (P = 0.018). However, no statistical difference was observed in BALF CEA (P =
      0.375) or CYFRA21-1 (P = 0.838) between lung cancer patients and nonmalignant
      controls. With a cut-off value of 2.06 ng/ml, NSE had a sensitivity of 72.9%, a
      specificity of 69.2%, respectively, in predicting the malignant nature of
      pulmonary mass. Our study observed that the level of VEGF-C was increased in BALF
      of patients with squamous cell carcinoma. Moreover, we found that NSE was
      significantly higher in BALF of lung cancer patients than in benign diseases. 

PMID- 24326980
TI  - Effect of oral piperine on the swallow response of patients with oropharyngeal
      dysphagia.
AB  - BACKGROUND: Oropharyngeal dysphagia (OD) is a major gastrointestinal motility
      disorder that causes severe nutritional and respiratory complications in elderly
      and neurological patients. In an earlier study, we found that stimulation of
      pharyngeal sensory neurons by capsaicinoids acting on transient receptor
      potential vanilloid 1 (TRPV1) improved the swallow response of dysphagic
      patients. The aim of this study was to explore the effect of piperine, a dual
      TRPV1/TRPA1 agonist, on the swallow response of dysphagic patients. METHODS: A
      videofluoroscopic study was performed to assess the signs of impaired safety and
      efficacy of swallow and the swallow response of 40 dysphagic patients while
      swallowing one series of nectar control boluses and two series of nectar boluses
      supplemented with piperine. Patients were randomized into two groups: one group
      received 150 MUM piperine and the other group received 1 mM. RESULTS: Piperine
      improved the safety of swallow by: (a) reducing the prevalence of unsafe swallows
      by -34.48% (P = 0.004) at 150 MUM and -57.19% (P < 0.001) at 1 mM, and the
      severity score of the penetration-aspiration scale from 3.25 +/- 0.51 to 1.85 +/-
      0.27 (P = 0.003, 1 mM); and (b) shortening the time to laryngeal vestibule
      closure from 0.366 +/- 0.024 to 0.270 +/- 0.022 s with 150 MUM piperine (P <
      0.001) and from 0.380 +/- 0.032 to 0.306 +/- 0.028 s with 1 mM piperine (P <
      0.05). CONCLUSIONS: Supplementing the alimentary bolus with piperine speeds
      swallow response and strongly improves safety of swallow in patients with OD,
      with a maximal therapeutic effect at 1 mM. Our results suggest that activation of
      TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation
      strategy for dysphagic patients.

PMID- 24326978
TI  - Activating secondary metabolism with stress and chemicals.
AB  - The available literature on the secondary or nonessential metabolites of the
      streptomycetes bacteria suggests that there may be poorly expressed or "cryptic"
      compounds that have yet to be identified and that may have significant medical
      utility. In addition, it is clear that there is a large and complex regulatory
      network that controls the production of these molecules in the laboratory and in
      nature. Two approaches that have been taken to manipulating the yields of
      secondary metabolites are the use of various stress responses and, more recently,
      the use of precision chemical probes. Here, we review the status of this work and
      outline the challenges and opportunities afforded by each of them. 

PMID- 24326981
TI  - The effect of antioxidant vitamins E and C on cognitive performance of the
      elderly with mild cognitive impairment in Isfahan, Iran: a double-blind,
      randomized, placebo-controlled trial.
AB  - PURPOSE: This study was carried out to investigate the effect of vitamins E and C
      on cognitive performance among the elderly in Iran. METHODS: About 256 elderly
      with mild cognitive impairment, aged 60-75 years, received 300 mg of vitamin E
      plus 400 mg of vitamin C or placebo daily just for 1 year. BACKGROUND:
      Demographic characteristics, anthropometric variables food consumption, cognitive
      function by Mini-Mental State Examination (MMSE), and some of the oxidative
      stress biomarkers were examined. RESULTS: Antioxidant supplementation reduced
      malondialdehyde level (P < 0.001) and raised total antioxidant capacity (P <
      0.001) and glutathione (P < 0.01). The serum 8-hydroxydeoxyguanosine remained
      unchanged (P < 0.4). After adjusting for the covariates effects, MMSE scores
      following 6- (25.88 +/- 0.17) and 12-month antioxidant supplementation (26.8 +/-
      0.17) did not differ from control group (25.86 +/- 0.18 and 26.59 +/- 0.18,
      respectively). CONCLUSION: Despite significant improvement in most of the
      oxidative stress biomarkers, antioxidants' supplementation was not observed to
      enhance cognitive performance. A large number of kinetic and/or dynamic factors
      could be suspected.

PMID- 24326982
TI  - Measurement of coherence decay in GaMnAs using femtosecond four-wave mixing.
AB  - The application of femtosecond four-wave mixing to the study of fundamental
      properties of diluted magnetic semiconductors ((s,p)-d hybridization, spin-flip
      scattering) is described, using experiments on GaMnAs as a prototype III-Mn-V
      system.  Spectrally-resolved and time-resolved experimental configurations are
      described, including the use of zero-background autocorrelation techniques for
      pulse optimization.  The etching process used to prepare GaMnAs samples for four
      wave mixing experiments is also highlighted.  The high temporal resolution of
      this technique, afforded by the use of short (20 fsec) optical pulses, permits
      the rapid spin-flip scattering process in this system to be studied directly in
      the time domain, providing new insight into the strong exchange coupling
      responsible for carrier-mediated ferromagnetism.  We also show that spectral
      resolution of the four-wave mixing signal allows one to extract clear signatures
      of (s,p)-d hybridization in this system, unlike linear spectroscopy techniques.  
      This increased sensitivity is due to the nonlinearity of the technique, which
      suppresses defect-related contributions to the optical response. This method may
      be used to measure the time scale for coherence decay (tied to the fastest
      scattering processes) in a wide variety of semiconductor systems of interest for
      next generation electronics and optoelectronics. 

PMID- 24326983
TI  - Prognostic value of FDG uptake in primary inoperable non-small cell lung cancer.
AB  - The purpose of this study was to assess the prognostic value of 18F-fluoro-2
      deoxy-glucose positron emission tomography (FDG-PET) in therapy for non-small
      cell lung cancer (NSCLC) and to further analyze the possible risk factors
      contributing to overall survival (OS) and progression-free survival (PFS). We
      retrospectively analyzed fifty patients between June 2007 and June 2010 with
      NSCLC who underwent positron emission tomography/computed tomography. We examined
      the correlation of the maximum standardized uptake value (SUVmax) in FDG-PET of
      the primary tumor with other possible factors. The FDG uptake in the primary
      tumor was also compared for the different Union for International Cancer Control
      (UICC) staging groups and further correlation was analyzed. We divided the
      patients into two groups by the receiver operating characteristic curve of
      SUVmax: SUVmax < 5.45 (low-SUV) and >= 5.45 (high-SUV). The prognostic value of
      each parameter for OS and PFS was determined by using univariate and multivariate
      analysis. There were significant correlations between SUVmax and Tumor length, N
      stage, UICC stage, histologic differentiation (r = 0.298, 0.855, 0.345, 0.435).
      The comparison between the low- and high-SUV groups was evaluated. Statistically
      significant differences were found in the SUVmax of the primary tumors among
      different UICC staging groups, and the correlation between stages I-II and stages
      III-IV for OS and PFS was also statistically significant. Univariate analysis
      showed that performance status (PS-ZPS score), histologic differentiation, UICC
      stages, and SUVmax of the primary tumor were significantly associated with OS and
      PFS. Multivariate logistic analysis showed that histologic differentiation and
      SUVmax of primary tumor might be considered as significant predictive factors for
      OS and PFS in patients with NSCLC. Our results showed that there was a
      significant relationship between the SUVmax of the primary tumor and OS and PFS.
      FDG uptake by the primary tumor may be an independent outcome predictor for
      patients with NSCLC.

PMID- 24326984
TI  - Cytokeratin 5/6, c-Met expressions, and PTEN loss prognostic indicators in triple
      negative breast cancer.
AB  - In subgroups of breast cancer, the shortest disease-free and overall survival was
      observed in basaloid and human epidermal growth factor receptor-2 groups. CK5/6
      expression is a marker used in diagnosing breast cancers in basaloid group and is
      associated with a poor prognosis. Similarly, loss of tumor suppressor gene PTEN
      and a high expression of c-Met has been associated with poor prognosis in breast
      cancer and many other cancers. In this study, we aimed to determine the effect of
      CK5/6 and c-Met expressions, and PTEN loss on the disease prognosis in triple
      negative breast cancer patients. Ninety-seven patients pathologically diagnosed
      with triple-negative breast cancer were enrolled. The clinical and pathological
      characteristics of the patients were recorded. c-Met, PTEN, and CK5/6 expressions
      were evaluated with immunohistochemical methods from paraffin blocks. The median
      age of patients was 47 years. CK5/6 positivity was 50.5 %, PTEN loss was 44.3 %,
      and high c-Met expression was detected in 53.6 %. In multivariate analysis,
      predictors of the recurrence were loss of PTEN (HR = 2.99; P = 0.004), high c-Met
      expression (HR = 2.05; P = 0.06), CK5/6 expression (HR = 2.99; P = 0.02),
      increase in the number of metastatic lymph nodes (HR = 1.11; P = 0.001), and an
      increase in tumor size (HR = 1.226; P = 0.01). Also, PTEN loss (HR = 2.43; P =
      0.05), CK5/6 expression (HR = 3.74; P = 0.01), and N2-3 tumors compared to
      negatives (HR = 3.63; P = 0.01) were associated with death. PTEN loss correlated
      with those of lymphovascular invasion. There was a correlation between CK5/6
      expression and the number of metastatic lymph nodes. Also, a correlation was
      found among cancers with highly expressed levels of c-Met, T1-2 tumors, and high
      grade tumors. The classical markers, lymph node involvement and tumor size, were
      found to be of prognostic value; however, high c-Met and CK5/6 expressions, and
      PTEN loss were found to increase risk of recurrence and death in patients with
      triple-negative breast cancer.

PMID- 24326985
TI  - Single measurement of hemoglobin predicts outcome of HCC patients.
AB  - Anemia is a common complication in several types of cancer including
      hepatocellular carcinoma (HCC). The prognostic potential of hemoglobin (Hb)
      levels has not yet been investigated in HCC patients. One hundred and ninety-nine
      patients were prospectively recruited and Hb levels were determined. Hb levels
      were compared to the stages of liver cirrhosis and HCC stages. The association of
      the Hb levels and overall survival (OS) was assessed by univariate and
      multivariate Cox regression models. The relation of Hb levels and OS was further
      validated in an independent cohort of 87 HCC patients. Hb levels negatively
      correlated with the stage of liver cirrhosis (model of end stage liver disease
      score and Child-Pugh stage) and differed between stages of HCC. Low Hb levels (<=
      13 g/dl) were associated with higher mortality in the test [hazard ratio (HR)
      2.422, 95 % confidence interval (CI) 1.357-4.322, P = 0.003] as well in the
      validation cohort (HR 2.486, 95 % CI 1.097-5.632, P = 0.029) in univariate Cox
      regression model. Low Hb levels were associated with mortality independently from
      the tumor stage, age, gender and the C-reactive protein levels in a multivariate
      Cox regression model. Anemia should be considered as a risk factor for mortality
      in HCC patients.

PMID- 24326986
TI  - Selection of hospital antimicrobial prescribing quality indicators: a consensus
      among German antibiotic stewardship (ABS) networkers.
AB  - PURPOSE: Simple, valid, and evidence-based indicators to measure the quality of
      antimicrobial prescribing in acute-care hospitals are urgently needed and
      increasingly requested by policymakers. The aim of this study was to develop new
      consensus quality indicators (QIs) for hospital antibiotic stewardship (ABS) and
      infection management which will be further evaluated for internal quality
      management and external quality assessment in Germany. METHODS: Based on an
      extensive literature review, the Austrian-German hospital ABS Guideline Committee
      and selected members of the German ABS Expert Network discussed and drafted a
      list of 99 potential indicators for hospitals that reflect structural
      prerequisites for ABS (35 items), ABS core activities (18 items), additional ABS
      measures (5 items), and process of care indicators (both generic and disease
      specific-12 and 29 items, respectively). Questionnaires were mailed to German ABS
      experts and healthcare professionals with further education in ABS. Participants
      scored (on a nine-point Likert scale) relevance (clinical, ecological/resistance,
      economical/expenses) and presumed practicability (six categories: clarity of
      definition, effort to collect data, barrier to implementation, verifiability,
      suitability for external quality assessment, quality gap), taking into account
      their local work environment. The scores were processed according to the
      RAND/UCLA appropriateness method, and QIs were judged relevant if the median
      (clinical + ecological and/or economical) scores were >6. The indicators thus
      assessed to be potentially relevant were then filtered according to their
      practicability. Highly relevant QIs with borderline practicability scores and
      items with disagreements and overlapping areas were re-discussed in a final
      multidisciplinary panel consensus workshop convened in November 2012. RESULTS: Of
      the 340 questionnaires that were mailed, 75 questionnaires were completed and
      returned. Of 99 initially proposed items, 32 were excluded due to insufficient
      scores. Of the remaining 67 items, 21 structural and 21 process of care QIs were
      finally selected, including four QIs with high clinical and ecological but
      limited economical relevance, and three QIs with high clinical and economical but
      limited ecological relevance. Among the selected QIs, efforts to collect data and
      implementation barriers were scored as suboptimal in many cases. CONCLUSIONS: A
      catalog of consensus structural and process of care ABS-QIs was established.
      These should undergo further pilot and feasibility studies in the German hospital
      healthcare sector. The panelists were most critical regarding resource
      use/complexity issues and presumed implementation barriers. How this may limit
      applicability of QIs remains to be determined.

PMID- 24326987
TI  - Fusobacterium species infections: clinical spectrum and outcomes at a district
      general hospital.
AB  - PURPOSE: Fusobacterium species infections are rare. Recently, however, this
      potentially deadly pathogen has been attracting interest, and efforts are being
      made to characterise its epidemiology and clinical spectrum of disease. The aim
      of our study is to provide further evidence towards this cause, in what is, to
      date, the largest study of its kind from the UK. METHOD: A 22-year,
      retrospective, descriptive study was performed at Royal Hampshire County
      Hospital. An electronic database was used to identify patients with
      microbiologically confirmed infection with Fusobacterium, and clinical records
      were examined to provide further information on the presentation, source,
      treatment and outcome. RESULTS: Fusobacterium species infections were identified
      in 18 patients during the study period, which is an incidence of 0.76
      cases/100,000/year. The overall death rate was 29 %. Half of these patients had
      Fusobacterium necrophorum infections and were a predominantly young, fit and
      uniquely male population who had excellent outcomes. Among the remaining patients
      with Fusobacterium species infections, 22 % had infection with F. varium and 11 %
      with F. nucleatum. These patients were an older cohort who tended to have co
      morbidities and unsurprisingly worse outcomes. We identified a number of
      Fusobacterium bacteraemias likely to have resulted from pressure ulcers, a
      presentation that has been rarely reported. Interestingly, we also identified a
      case of neonatal F. nucleatum bacteraemia that was not associated with premature
      nor stillborn birth. CONCLUSION: As work continues to depict the spectrum of
      disease caused by this enigmatic bacterium, it is hoped that improved clinical
      suspicion will result in better outcomes and management.

PMID- 24326989
TI  - Not there yet: Medicare Part D and elimination of cardiovascular medication usage
      sociodemographic disparities after myocardial infarction.

PMID- 24326988
TI  - Racial/Ethnic and gender gaps in the use of and adherence to evidence-based
      preventive therapies among elderly Medicare Part D beneficiaries after acute
      myocardial infarction.
AB  - BACKGROUND: It is unclear whether gender and racial/ethnic gaps in the use of and
      patient adherence to beta-blockers, angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers, and statins after acute myocardial
      infarction have persisted after establishment of the Medicare Part D prescription
      program. METHODS AND RESULTS: This retrospective cohort study used 2007 to 2009
      Medicare service claims among Medicare beneficiaries >=65 years of age who were
      alive 30 days after an index acute myocardial infarction hospitalization in 2008.
      Multivariable logistic regression models examined racial/ethnic (white, black,
      Hispanic, Asian, and other) and gender differences in the use of these therapies
      in the 30 days after discharge and patient adherence at 12 months after
      discharge, adjusting for patient baseline sociodemographic and clinical
      characteristics. Of 85 017 individuals, 55%, 76%, and 61% used angiotensin
      converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and
      statins, respectively, within 30 days after discharge. No marked differences in
      use were found by race/ethnicity, but women were less likely to use angiotensin
      converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers
      compared with men. However, at 12 months after discharge, compared with white
      men, black and Hispanic women had the lowest likelihood (~30%-36% lower; P<0.05)
      of being adherent, followed by white, Asian, and other women and black and
      Hispanic men (~9%-27% lower; P<0.05). No significant difference was shown between
      Asian/other men and white men. CONCLUSIONS: Although minorities were initially no
      less likely to use the therapies after acute myocardial infarction discharge
      compared with white patients, black and Hispanic patients had significantly lower
      adherence over 12 months. Strategies to address gender and racial/ethnic gaps in
      the elderly are needed.

PMID- 24326990
TI  - Can we learn about the hypertension-induced decline in renal function from
      noninvasive haemodynamics?

PMID- 24326991
TI  - Renal denervation: still more questions than answers.

PMID- 24326992
TI  - Assessment of the reductions in night-time blood pressure and dipping induced by
      antihypertensive medication using a home blood pressure monitor.
AB  - BACKGROUND: Night-time blood pressure (BP) is strongly associated with
      hypertensive target organ damage; however, no previous studies have compared home
      BP monitor measurements of the reduction in night-time BP induced by
      antihypertensive medications with those obtained with ambulatory BP monitors.
      METHODS: As part of the Japan Morning Surge-Target Organ Protection study, in
      which candesartan (thiazide diuretics were added, if needed) was administered to
      hypertensive patients in the morning or at bedtime, 50 hypertensive patients had
      their night-time home and ambulatory BP successfully measured at the baseline and
      6 months. In addition, three night-time home BP readings were taken during
      sleeping hours (at 2, 3, and 4 o'clock) for 6 months. RESULTS: The mean reduction
      in night-time BP did not differ significantly between home and ambulatory BP
      monitoring (10.4 +/- 17.9/6.0 +/- 12.0 vs. 13.3 +/- 14.6/7.6 +/- 8.9 mmHg, P =
      0.219/0.344), but the differences varied among individual patients. The reduction
      in night-time BP according to home BP monitoring was significantly correlated
      with the value obtained with ambulatory BP monitoring (r = 0.51/0.38, P <
      0.001/=0.006). The reduction in night-time SBP according to home BP monitoring
      was significantly correlated with the reductions in left ventricular mass index
      (r = 0.385, P = 0.013, N = 41) and Sokolow-Lyon voltage (r = 0.335, P = 0.035, N
      = 40). CONCLUSION: Home BP monitoring produces estimates of mean night-time BP
      reductions comparable to those from ambulatory monitoring, while the differences
      varied among individual patients. The reduction in night-time home BP according
      to home BP monitoring is significantly correlated with the reduction in left
      ventricular hypertrophy.

PMID- 24326993
TI  - The effect of oral contraceptive pills and the natural menstrual cYCLe on
      arterial stiffness and hemodynamICs (CYCLIC).
AB  - BACKGROUND: Over 100 million women currently use oral contraceptive pills (OCPs)
      worldwide. However, little is known about the effects of OCPs on arterial
      stiffness and hemodynamics. Furthermore, whether arterial stiffness and
      hemodynamics vary throughout the natural menstrual cycle remains controversial.
      Herein, we estimated the effect of the natural menstrual cycle and OCP use on
      arterial stiffness and hemodynamics. METHODS: Healthy, nonsmoking women, aged 18
      30 years, were recruited if they had regular menstrual cycles and never used OCPs
      (OCP nonuser group), or were using low-dose OCPs for at least 6 months (OCP user
      group). Using applanation tonometry, three assessments of arterial stiffness and
      central and peripheral hemodynamics were performed in a randomized order: during
      the early follicular (days 3-6), late follicular (days 14-16), and luteal (days
      22-26) phases. Within group and between group comparisons were performed using
      general linear models. RESULTS: Sixty women (21.7 +/- 2.8 years) were recruited.
      Compared with OCP nonusers, OCP users had significantly increased aortic and
      peripheral SBPs during the active OCP use, but not during the inert tablet phase.
      No differences in arterial stiffness were noted. CONCLUSION: OCP use was
      associated with significant increases in aortic and peripheral blood pressures,
      but not with increased arterial stiffness. Given the widespread OCP use, future
      longitudinal studies are needed to confirm our findings and assess the long-term
      effect of OCPs on arterial stiffness and hemodynamics.

PMID- 24326994
TI  - Burns: a forgotten cause of hypertension in children.

PMID- 24326995
TI  - Comment on 'Munchausen syndrome: a novel cause of drug-resistant hypertension'.

PMID- 24326996
TI  - Antihypertensive treatment: a source of confusion when considered as a
      cardiovascular risk factor.

PMID- 24326997
TI  - Reply to 'antihypertensive treatment: a source of confusion when considered as a
      cardiovascular risk factor'.

PMID- 24326999
TI  - Influences of enteral nutrition upon CEACAM6 expression by intestinal epithelial
      cells.
AB  - Exclusive enteral nutrition is established as an initial therapy to induce
      remission in active Crohn's disease (CD), especially in children, but the
      mechanisms of action of this therapy are yet to be fully defined. CEACAM6 protein
      is an adhesion molecule that is up-regulated in active CD and implicated in the
      attachment of adherent-invasive Escherichia coli (AIEC) to the gut epithelium.
      Using the Caco-2 human adenocarcinoma cell line, this study showed that the
      incubation of human cells with a polymeric formula (PF) resulted in a dose
      dependent increase in the expression of CEACAM6, and that this effect was most
      noticeable on the cell surface. Further investigation revealed that PF doubled
      the release of CEACAM6 protein by Caco-2 cells exposed to PF, and that an
      increase in release of soluble CEACAM6 inversely correlated with the ability of
      AIEC to associate with the intestinal epithelial cells. Our findings suggest that
      the secretion of cell surface-associated proteins acting as releasable decoys may
      be an aspect of the gut's innate immune response to pathogenic bacteria that is
      strengthened by PF in the setting of CD. 

PMID- 24326998
TI  - Matrix identity and tractional forces influence indirect cardiac reprogramming.
AB  - Heart regeneration through in vivo cardiac reprogramming has been demonstrated as
      a possible regenerative strategy. While it has been reported that cardiac
      reprogramming in vivo is more efficient than in vitro, the influence of the
      extracellular microenvironment on cardiac reprogramming remains incompletely
      understood. This understanding is necessary to improve the efficiency of cardiac
      reprogramming in order to implement this strategy successfully. Here we have
      identified matrix identity and cell-generated tractional forces as key
      determinants of the dedifferentiation and differentiation stages during
      reprogramming. Cell proliferation, matrix mechanics, and matrix microstructure
      are also important, but play lesser roles. Our results suggest that the
      extracellular microenvironment can be optimized to enhance cardiac reprogramming.

PMID- 24327001
TI  - COPD classification methods and informativeness on mortality: contrasting
      evidences.
AB  - Understanding whether the ABCD GOLD classification method is informative with
      respect to the spirometric classification of severity in predicting mortality of
      patients with chronic obstructive pulmonary disease (COPD) is subject of debate.
      The results of a study performed on a sample of the Norwegian population (HUNT2)
      were recently published. Such data showed the inferiority of ABCD classification
      in predicting mortality compared to the spirometric classification, which was
      considered the gold standard up to the 2011 version of GOLD guidelines. This
      result is not in line with the results of other studies that have shown the
      equivalence of the two classifications. The new GOLD classification seemed to be
      a step forward for what concerns understanding patient's needs, but it seems
      clear that the insertion of a single clinical variable to the spirometric data
      may not be exhaustive in describing all the phenomena related to a heterogeneous
      disease such as COPD. The publication of the HUNT study provides an opportunity
      to analyze how the evidence has been produced, which scientific speculations it
      offers, what considerations could be drawn and what further research would be
      appropriate. 

PMID- 24327002
TI  - New life for macrolides.
AB  - This article is an attempt to analyze and discuss the role and the purported
      mechanisms of azithromycin (AZM) in non-eosinophilic severe asthma, including
      antineutrophil activity, an effect on gastroesophageal reflux or antibacterial
      activity against an underlying chronic infection, such as Chlamydia pneumoniae.
      Macrolides have an expanding role in the therapy of chronic inflammatory diseases
      based on their additional anti-inflammatory and immunosuppressive properties.
      Many studies have been performed in lung transplantation field and maintenance
      treatment has been proved to be effective in cystic fibrosis, bronchiectasis,
      diffuse panbronchiolitis, and in bronchiolitis obliterans syndrome and in the
      prevention of exacerbations in patients with chronic obstructive pulmonary
      disease. Pathobiological studies of people with severe, refractory asthma focused
      on its heterogeneity encouraging more targeted and personalized approaches to
      asthma therapy. In neutrophilic asthma corticosteroids are not very effective,
      while the immunomodulatory action of macrolides is particularly relevant on
      neutrophils. Recently, The AZIthromycin in Severe ASThma (AZISAST) study,
      published on the April number of Thorax, provided evidences on the efficacy and
      safety of long-term add-on treatment with AZM in severe non-eosinophilic asthma.
      Despite concerns about an increased proportion of macrolide-resistant organism
      and about the effects of macrolides on cardiovascular events, there was no
      evidence of an increased risk of pneumonia or other adverse events. Because the
      AZISAST study was not able to demonstrate significant improvement in lung
      function and use of rescue medication, there is still a need for new data
      confirming the efficacy of AZM in severe non-eosinophilic asthma. 

PMID- 24327000
TI  - Endothelial injury markers before and after nasal continuous positive airway
      pressure treatment for obstructive sleep apnoea hypopnoea syndrome.
AB  - PURPOSE: The purpose of this study was to evaluate whether serum amyloid A (SAA),
      C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1) and
      intercellular adhesion molecule-1 (ICAM-1) levels are elevated in obstructive
      sleep apnoea hypopnoea syndrome (OSAHS), and whether they change following acute-
      and medium-term CPAP treatment. METHODS: Consecutive subjects (n = 40) referred
      to the Sleep Disordered Breathing Unit were included in the research. Sera were
      sampled in the afternoon prior to an in-hospital limited-channel sleep study and
      on the next morning. Those diagnosed with OSAHS were commenced on CPAP and had
      further blood samples collected in the morning after the first night and then
      after a month of treatment. RESULTS: We had 20 subjects with moderate/severe
      OSAHS (mean +/- SD), 4% desaturation rate (4% DR) 44.3 +/- 31.4 events/h, and 20
      comparator subjects with symptoms but negative sleep studies, 4% DR 5.6 +/- 2.9
      events/h. There was no difference in the morning and afternoon vascular injury
      marker levels between the OSAHS and comparator groups. However, CRP (6.52 +/-
      9.53 vs. 5.58 +/- 8.47, p = 0.04) and VCAM-1 (366.30 +/- 90.11 vs. 339.60 +/-
      95.87, p = 0.02) levels showed significant diurnal variation within the OSAHS
      group with higher afternoon levels compared to morning measurements. There were
      no changes in any of the vascular injury marker levels following CPAP.
      CONCLUSIONS: This study demonstrates that OSAHS leads to endothelial dysfunction
      as reflected by higher afternoon than morning CRP and VCAM-1 levels. However,
      despite a good CPAP compliance, a month of treatment does not decrease vascular
      injury marker levels.

PMID- 24327003
TI  - Lung cancer: can staging improvement ensure a better survival?
AB  - Lung cancer is among the most common cancers in the world. Despite advances in
      defining the molecular mechanisms involved in lung oncogenesis and the remarkable
      efforts made to improve screening programs for secondary cancer prevention,
      patients' prognosis remains poor. Moreover, wide international inequalities
      remain apparent, even among developed countries. Here we analyze and discuss the
      findings of the extensive work by Walters S et al., recently published in
      "Thorax", which aimed to clarify whether differences in stage at diagnosis might
      explain these divergences. A better understanding of why survival differences
      between different states still exist will facilitate policy design to increase
      lung cancer overall survival itself and to bring it up to the highest
      international standards. It is the first international population-based study of
      lung cancer survival by stage at diagnosis and includes nearly 60,000 patients.
      By using a well detailed and appropriate statistical approach, authors conclude
      that improvement in outcomes is primarily related to a proper initial disease
      staging and that socioeconomic international and interregional inequalities might
      play a relevant role in this scenario. Our review takes in consideration both the
      methodological and scientific issues of the paper, focusing on the potential
      consequences in lung cancer management and on the need, in the post genomic era,
      of a molecular-based epidemiologic approach. 

PMID- 24327004
TI  - Revealing the properties of Mn2Au for antiferromagnetic spintronics.
AB  - The continuous reduction in size of spintronic devices requires the development
      of structures, which are insensitive to parasitic external magnetic fields, while
      preserving the magnetoresistive signals of existing systems based on giant or
      tunnel magnetoresistance. This could be obtained in tunnel anisotropic
      magnetoresistance structures incorporating an antiferromagnetic, instead of a
      ferromagnetic, material. To turn this promising concept into real devices, new
      magnetic materials with large spin-orbit effects must be identified. Here we
      demonstrate that Mn2Au is not a Pauli paramagnet as hitherto believed but an
      antiferromagnet with Mn moments of ~4 MUB. The particularly large strength of the
      exchange interactions leads to an extrapolated Neel temperature well above 1,000
      K, so that ground-state magnetic properties are essentially preserved up to room
      temperature and above. Combined with the existence of a significant in-plane
      anisotropy, this makes Mn2Au the most promising material for antiferromagnetic
      spintronics identified so far.

PMID- 24327005
TI  - Evaluation of coracoclavicular stabilization of acute acromioclavicular joint
      dislocation with multistrand titanium cables.
AB  - PURPOSE: The aim of this study was to evaluate the outcome of surgical treatment
      of acute acromioclavicular (AC) joint dislocation with multistrand titanium
      cables for coracoclavicular (CC) stabilization. METHODS: Forty-two patients with
      acute AC joint dislocation, including Rockwood type III 14 cases, type IV 2 cases
      and type V 26 cases, were operated with CC stabilization using multistrand
      titanium cables. The cables were removed 3-12 months after surgery. The function
      outcome was evaluated by Constant scores and visual analog scale (VAS) scores.
      Radiological examination included bilateral antero-posterior and axillary
      radiography. RESULTS: Three patients were lost to follow-up. Thirty-nine patients
      had an average follow-up time of 42 months (range 34-60). The Constant scores
      were 95.3 +/- 9.3 at final evaluation. Preoperative and final follow-up VAS
      scores were 5.6 +/- 1.5 and 0.4 +/- 1.2, respectively (P < 0.05). Radiographs
      showed anatomical reduction in 32 patients. Cables breakage occurred in two
      patients. CONCLUSIONS: CC stabilization with multistrand titanium cables was an
      effective and safe alternative to other procedures for the treatment of acute
      high-grade AC joint dislocations. It can provide immediate joint stabilization
      and allow early mobilization of limb with satisfied functional recovery.

PMID- 24327006
TI  - Management of Mason type 1 radial head fractures: a regional survey and a review
      of literature.
AB  - INTRODUCTION: Despite being the most common fracture around the elbow, the
      management of Mason type 1 radial head fractures lacks a clear protocol in
      literature. The aims of this study were to assess our practice of managing this
      injury and to create guidance for the management of these fractures based on
      literature review. METHODS: We designed a survey investigating the practice of
      orthopaedic surgeons in the management of Mason type 1 fracture. The literature
      review was carried out looking for the best practice guidelines. RESULTS: Forty
      nine surgeons (out of 56) responded, and mean duration of immobilisation was
      11.69 days with the collar and cuff sling as the preferred method. 65.3% offered
      physiotherapy service to their patients. 20.4% recommended plain radiographic
      imaging follow-up. Mean duration of follow-up was 43.9 days. Decision to
      discharge the patient was mostly (77.6%) dependent on clinical improvement at
      time of last examination. 4.1% of treatment decisions were evidence based.
      CONCLUSION: We observed a wide variation in the management of this common injury.
      Based on the current literature, the best protocol for the management of type 1
      radial head fractures should be joint aspiration, followed by immobilisation in a
      broad arm sling for 2 days. At the first outpatient visit, assessment of the
      collateral stability should be performed. Patients with stable elbows should be
      encouraged to stretch these beyond the painful range. Patients can be discharged
      at this stage with an advice to come back for a clinical and radiographic
      assessment if there is no improvement at 6 weeks.

PMID- 24327007
TI  - Manipulation for stiffness following total knee arthroplasty: when and how often
      to do it?
AB  - Stiffness following total knee arthroplasty is a disabling complication. One of
      the management options of stiffness includes manipulation under anaesthesia, but
      no real consensus exist on appropriate timing of intervention, and the timing and
      results of the manipulation under anaesthesia (MUA) are under debate in the
      literature. Our aim was to determine the efficacy of single and multiple
      manipulations under anaesthesia following total knee arthroplasty and to
      determine the most appropriate timing for manipulation. We retrospectively
      reviewed 86 patients who underwent manipulation for stiffness following primary
      total knee replacement with at least 1-year follow-up. Range of motion before
      surgery, at the time of the MUA, immediately after MUA and at 6 weeks and 1 year
      post-MUA were recorded. At the end of 1 year post-manipulation, manipulations
      performed at less than 20 weeks, following primary total knee arthroplasty,
      showed 31 degrees  of flexion gain as compared to only 1.5 degrees  of flexion
      gain when manipulation was undertaken after 20 weeks. Of the 86 patients, 21 had
      multiple manipulations with no significant difference in flexion gain after the
      second manipulation. Patients on warfarin (26%) had an increased incidence of
      stiffness and poor flexion gain. This study showed that better results were
      achieved when manipulation was performed at less than 20 weeks (particularly
      between 12 and 14 weeks) from primary surgery with no added benefit from re
      manipulations.

PMID- 24327008
TI  - Good practice models for public workplace health promotion projects in Austria:
      promoting mental health.
AB  - Promoting mental health is a central public health issue since the Jakarta
      statement in 1997. In Austria, the nationwide organisation for health promotion
      is the 'Fonds Gesundes Osterreich' (FGO), which has been established in 1998. The
      FGO funds and supports workplace health promotion projects; therefore, it co
      operates with the Austrian Network on Workplace Health Promotion. In 2011, among
      others, two Austrian companies were honoured as best practice models for
      promoting mental health in the project 'Work. In tune with life. Move Europe'.
      One of their central key success factors are the provision of equal
      opportunities, engagement, their focus on overall health as well as the
      implementation of behavioural and environmental preventive measures. Since mental
      health problems in the population are still rising, public health promotion
      projects which orientate on the best practice models have to be established in
      Austria.

PMID- 24327009
TI  - Out-of-plane ion concentration polarization for scalable water desalination.
AB  - We present a scalable, out-of-plane desalination approach using ion concentration
      polarization. A depletion boundary separates salt ions and purified water into
      distinct vertical layers. The out-of-plane design enables multiplexing in three
      dimensions, providing the functional density required for practical application.
      For membrane widths of 125-200 MUm, and applied voltage of 5 V, the energy
      requirement is 4.6 Wh L(-1) for 20 mM solution, and 13.8 Wh L(-1) for 200 mM.
      Energy efficiency is found to be insensitive to flow rate as the depletion
      boundary adjusts to yield a commensurate volume of purified water. Scaled-up
      devices are presented, which have a 3-fold improvement in functional density over
      planar systems. 

PMID- 24327010
TI  - Negative effect of P72 polymorphism on p53 gene in IVF outcome in patients with
      repeated implantation failure and pregnancy loss.
AB  - PURPOSE: Investigate whether R72P on p53 gene polymorphism has a higher
      prevalence among women with a history of recurrent implantation failure (RIF) and
      pregnancy loss (RPL) and its influence in their IVF cycle outcome. MATERIAL AND
      METHODS: p53 polymorphism R72P has been studied in 181 women. The control group
      included 83 oocyte donors. In the study group 98 women were included: 44 with RIF
      and 54 with RPL. From the study group, 76 patients underwent IVF-cycles (55 RPL
      and 21 RIF). RESULTS: The frequency of PP genotypes on p53 among RIF was 11.4%
      compared with 18.5% for RPL and 6% in controls (p < 0.01). There were no
      significant differences with respect to patient characteristics. Significant
      differences were reported in pregnancy rate (69.4% for RR/RP and 33.3% for PP; p
      < 0.05), embryo implantation rate (33.3% for RR/RP and 7.3% for PP; p < 0.05) and
      ongoing pregnancy rate (53.1% for RR/RP and 14.3% for PP; p < 0.05) among RIF and
      RPL. CONCLUSIONS: This investigation reveals that in RIF and RPL patients R72P on
      p53 gene is more prevalent than fertile population. Moreover, patients carrying a
      PP genotype on p53 codon 72 will have less chance to achieve an ongoing
      pregnancy. This information together with some additional markers will allow
      development of diagnostic tests for detects risk for RIF and RPL before
      infertility treatment is initiated.

PMID- 24327011
TI  - Molecular dynamics simulations of PNA-PNA and PNA-DNA duplexes by the use of new
      parameters implemented in the GROMACS package: a conformational and dynamics
      study.
AB  - Peptide Nucleic Acids (PNAs) still represent a growing research area thanks to
      their potential applications in many fields of science from chemistry and biology
      to medicine. In these years, structural investigations by means of either
      experimental or computational techniques have proved to be very useful for the
      understanding of the structural organization and the binding properties of PNA.
      In this context, we here report an all-atoms Molecular Dynamics (MD) study of a
      PNA-PNA duplex and a PNA-DNA hetero-duplex with the well known GROMACS simulation
      package, by using new force field parameters properly derived for PNA molecules.
      The good agreement of our results with the crystallographic and NMR data,
      available for both the systems under investigation, confirms the validity of our
      approach. Moreover, our simulations reveal new interesting features related to
      the conformational-dynamic behavior of the studied systems, thus demonstrating
      the ability of MD simulations to gain insights into the dynamic properties of
      biologically relevant systems. This force field parametrization represents a good
      starting point for the implementation of a computational platform, based on the
      GROMACS package, useful for the rational design of modified PNA molecules with
      improved conformational features for selective binding toward DNA or RNA. 

PMID- 24327012
TI  - Tumors and tumor-like lesions mimicking carpal tunnel syndrome.
AB  - INTRODUCTION: Tumors and tumor-like lesions in or around the median nerve are
      uncommon causes of carpal tunnel syndrome (CTS). The purpose of the present study
      is to highlight the diagnostic approach and point out the profile of patients
      with CTS and potential underlying pathology. MATERIALS AND METHODS: Twenty-eight
      patients with 32 affected hands had CTS correlated to a mass in or around the
      nerve. In 20 hands a palpable mass was present. Diagnostic workup included nerve
      conduction studies, ultrasound and/or MRI. Pre- and postoperative examination
      included two-point discrimination (2PD), grip strength, visual analogue scale
      (for pain) (VAS) and disabilities of the arm, shoulder and hand (DASH) scores.
      RESULTS: Twelve of 28 patients were young (range 9-38 years) and 10 were male.
      Nerve compression was due to 27 extraneural lesions (8 abnormal muscles, 5
      lipomas, 7 tenosynovitis, 4 vascular tumors, 2 ganglia, 1 Dupuytren's
      fibromatosis) and five intraneural tumors (three schwannomas, one neurofibroma,
      one sarcoma). Nerve decompression and excision of extraneural lesions were
      performed in all cases whereas in intraneural tumors, decompression was followed
      by excision in most cases and nerve grafting in one. Mean follow-up was 22 months
      (12-105 months). Extraneural masses were associated with a better outcome than
      nerve tumors. The mean postoperative VAS/DASH scores were 0.3/16.2 in extraneural
      lesions and 2.5/22 in intraneural lesions. The 2PD improved gradually in all
      patients (mean pre- and postoperative 12 and 5 mm). The mean grip strength
      increased from 28 to 31.3 kg postoperatively. CONCLUSIONS: Although rare, the
      surgeon should include in the differential diagnosis of CTS the unusual cause of
      tumors and tumor-like lesions, especially when the patients' profile is not
      typical (young, male, no repetitive stress or manual labor). In addition, the
      presence of a palpable mass at the distal forearm or palm dictates the need for
      imaging studies. The extent, location and aggressiveness of the mass will
      determine the approach and type of procedure.

PMID- 24327013
TI  - Brain metastasis in renal cancer patients: metastatic pattern, tumour-associated
      macrophages and chemokine/chemoreceptor expression.
AB  - BACKGROUND: The mechanisms of brain metastasis in renal cell cancer (RCC)
      patients are poorly understood. Chemokine and chemokine receptor expression may
      contribute to the predilection of RCC for brain metastasis by recruitment of
      monocytes/macrophages and by control or induction of vascular permeability of the
      blood-brain barrier. METHODS: Frequency and patterns of brain metastasis were
      determined in 246 patients with metastatic RCC at autopsy. Expression of CXCR4,
      CCL7 (MCP-3), CCR2 and CD68(+) tumour-associated macrophages (TAMs) were analysed
      in a separate series of 333 primary RCC and in 48 brain metastases using
      immunohistochemistry. RESULTS: Fifteen percent of 246 patients with metastasising
      RCC had brain metastasis. High CXCR4 expression levels were found in primary RCC
      and brain metastases (85.7% and 91.7%, respectively). CCR2 (52.1%) and CCL7
      expression (75%) in cancer cells of brain metastases was more frequent compared
      with primary tumours (15.5% and 16.7%, respectively; P<0.0001 each). The density
      of CD68(+) TAMs was similar in primary RCC and brain metastases. However, TAMs
      were more frequently CCR2-positive in brain metastases than in primary RCC
      (P<0.001). CONCLUSION: Our data demonstrate that the monocyte-specific chemokine
      CCL7 and its receptor CCR2 are expressed in tumour cells of RCC. We conclude that
      monocyte recruitment by CCR2 contributes to brain metastasis of RCC.

PMID- 24327014
TI  - Long-term dietary sodium, potassium and fluid intake; exploring potential novel
      risk factors for renal cell cancer in the Netherlands Cohort Study on diet and
      cancer.
AB  - BACKGROUND: As sodium, potassium and fluid intake are related to hypertension, an
      established risk factor for renal cell cancer (RCC), they may be independent risk
      factors for RCC. METHODS: The Netherlands Cohort Study (NLCS) with case-cohort
      design included 120,852 participants aged 55-69 years. At baseline, diet and
      lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485
      RCC cases and 4438 subcohort members were available for analyses. RESULTS: Sodium
      intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did
      not. For high sodium and low fluid intake, the RCC risk additionally increased (P
      interaction=0.02). CONCLUSION: Sodium intake is a potential risk factor for RCC,
      particularly if fluid consumption is low.

PMID- 24327015
TI  - An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic
      targets in malignant pleural mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour
      originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12
      month median survival, and new targets for treatments are desperately needed.
      METHODS: Utilising an RNA interference (RNAi)-based screen of 40 genes
      overexpressed in tumours, including genes involved in the control of cell cycle,
      DNA replication and repair, we investigated potential therapeutic targets for
      MPM. Following in vitro characterisation of the effects of target silencing on
      MPM cells, candidates were assessed in tumour samples from 154 patients. RESULTS:
      Gene knockdown in MPM cell lines identified growth inhibition following knockdown
      of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased
      apoptosis. Using small-molecule inhibitors specific for these three proteins also
      led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1)
      sensitised cells to cisplatin. Protein expression was also measured in tumour
      samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in
      over 10% of cells correlated significantly with a poor prognosis. CONCLUSION:
      These results suggest that RNAi-based screening has utility in identifying new
      targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for
      treatment of this disease.

PMID- 24327016
TI  - Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma
      metastasis.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) has a distinctive geographic
      distribution and is characterised by its strong tendency of metastasis. We aimed
      to examine the microRNA (miRNA) expression profiles in plasma samples of NPC
      patients to explore their clinical significance in disease development and
      progression. METHODS: This study was divided into four steps: (1) confirmation of
      differentially expressed miRNAs using microarray analysis and quantitative PCR
      validation; (2) comparison of plasma miR-9 levels during NPC progression; (3)
      evaluation of the predictive performance of plasma miR-9 as a biomarker for NPC
      metastasis; and (4) comparison of plasma miR-9 levels between pre- and post
      treatment samples. RESULTS: Plasma microarray profiling identified 33
      differentially expressed miRNAs between NPC patients and healthy volunteers. The
      significantly declined level of miR-9 in NPC patients was confirmed through two
      stage validation. The low level of plasma miR-9 was significantly correlated with
      worse lymphatic invasion and advanced TNM stage. The plasma miR-9 could
      distinguish locoregional from metastatic NPC cases with a high sensitivity and
      specificity. Furthermore, the plasma miR-9 level was significantly elevated in
      post-treatment plasma compared with those pre-treatment samples. CONCLUSION: Our
      study reports that plasma miR-9 may serve as a useful biomarker to predict NPC
      metastasis and to monitor tumour dynamics.

PMID- 24327021
TI  - From an upstairs window, winter: L. L. FitzGerald.

PMID- 24327017
TI  - ALDH1 is an independent prognostic factor for patients with stages II-III rectal
      cancer after receiving radiochemotherapy.
AB  - BACKGROUND: About one in five patients with locally advanced rectal cancer (RC)
      suffers recurrence or distant metastasis after neoadjuvant therapy. We
      investigated how cancer stem cell markers change after neoadjuvant therapy and
      how these markers relate to recurrence. METHODS: Pretreatment biopsies and
      postoperative specimens were taken from 64 patients with locally advanced rectal
      adenocarcinoma who received preoperative radiochemotherapy (RCT) between
      sampling. Samples were tested immunohistochemically for CD44, LGR5, ALDH1 and
      CD166; scores were dichotomised as high or low. The median follow-up period was
      36 months. RESULTS: High expression of CD44, LGR5, ALDH and CD166 was found in
      38%, 5%, 48% and 10%, respectively, before RCT and 86%, 33%, 71% and 52%,
      respectively, after RCT. CD44 (P=0.001), LGR5 (P=0.049) and CD166 (P=0.003) were
      significantly upregulated after RCT. Whereas no recurrence was seen during the
      follow-up in the low ALDH group, 40% of the high ALDH group suffered recurrence.
      In multivariate COX analysis, postoperative ALDH1 independently predicted poor
      prognosis in patients with RC who received RCT (P=0.0095). CONCLUSION:
      Preoperative RCT upregulates expression of stem cell markers in patients with RC.
      High post-treatment ALDH1 expression predicts poor prognosis for these patients
      after neoadjuvant therapy.

PMID- 24327022
TI  - IDSA: Better, faster diagnostics for infectious diseases needed to curb
      overtreatment, antibiotic resistance.

PMID- 24327018
TI  - Enhanced FGFR signalling predisposes pancreatic cancer to the effect of a potent
      FGFR inhibitor in preclinical models.
AB  - BACKGROUND: Fibroblast growth factor receptor (FGFR) signalling has been
      implicated in pancreas carcinogenesis. We investigated the effect of FGFR
      inhibition in pancreatic cancer in complementary cancer models derived from cell
      lines and patient-derived primary tumour explants. METHODS: The effects of FGFR
      signalling inhibition in pancreatic cancer were evaluated using anti-FRS2 shRNA
      and dovitinib. Pancreatic cancers with varying sensitivity to dovitinib were
      evaluated to determine potential predictive biomarkers of efficacy. Primary
      pancreatic explants with opposite extreme of biomarker expression were selected
      from 13 tumours for in vivo dovitinib treatment. RESULTS: Treatment with anti
      FRS2 shRNA induced significant in vitro cell kill in pancreatic cancer cells.
      Dovitinib treatment achieved similar effects and was mediated by Akt/Mcl-1
      signalling in sensitive cells. Dovitinib efficacy correlated with FRS2
      phosphorylation status, FGFR2 mRNA level and FGFR2 IIIb expression but not
      phosphorylation status of VEGFR2 and PDGFRbeta. Using FGFR2 mRNA level, a proof
      of-concept study using primary pancreatic cancer explants correctly identified
      the tumours' sensitivity to dovitinib. CONCLUSION: Inhibiting FGFR signalling
      using shRNA and dovitinib achieved significant anti-cancer cancer effects in
      pancreatic cancer. The effect was more pronounced in FGFR2 IIIb overexpressing
      pancreatic cancer that may be dependent on aberrant stimulation by stromal
      derived FGF ligands.

PMID- 24327023
TI  - FDA moves to further reduce trans fat in food.

PMID- 24327024
TI  - Nephrologists question ACP's kidney disease guidelines.

PMID- 24327025
TI  - Pregnancy after bariatric surgery associated with risks to offspring.

PMID- 24327035
TI  - Conflicts of interest in medical education: recommendations from the Pew task
      force on medical conflicts of interest.

PMID- 24327036
TI  - A piece of my mind. Scut.

PMID- 24327038
TI  - Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12
      deficiency.
AB  - IMPORTANCE: Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists
      (H2RAs) suppress the production of gastric acid and thus may lead to
      malabsorption of vitamin B12. However, few data exist regarding the associations
      between long-term exposure to these medications and vitamin B12 deficiency in
      large population-based studies. OBJECTIVE: To study the association between use
      of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the
      United States. DESIGN, SETTING, AND PATIENTS: We evaluated the association
      between vitamin B12 deficiency and prior use of acid-suppressing medication using
      a case-control study within the Kaiser Permanente Northern California population.
      We compared 25,956 patients having incident diagnoses of vitamin B12 deficiency
      between January 1997 and June 2011 with 184,199 patients without B12 deficiency.
      Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and
      diagnostic databases. MAIN OUTCOMES AND MEASURES: Risk of vitamin B12 deficiency
      was estimated using odds ratios (ORs) from conditional logistic regression.
      RESULTS: Among patients with incident diagnoses of vitamin B12 deficiency, 3120
      (12.0%) were dispensed a 2 or more years' supply of PPIs, 1087 (4.2%) were
      dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 21,749
      (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients
      without vitamin B12 deficiency, 13,210 (7.2%) were dispensed a 2 or more years'
      supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years' supply of H2RAs
      (without any PPI use), and 165,092 (89.6%) had not received prescriptions for
      either PPIs or H2RAs. Both a 2 or more years' supply of PPIs (OR, 1.65 [95% CI,
      1.58-1.73]) and a 2 or more years' supply of H2RAs (OR, 1.25 [95% CI, 1.17-1.34])
      were associated with an increased risk for vitamin B12 deficiency. Doses more
      than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency
      (OR, 1.95 [95% CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63
      [95% CI, 1.48-1.78]; P = .007 for interaction). CONCLUSIONS AND RELEVANCE:
      Previous and current gastric acid inhibitor use was significantly associated with
      the presence of vitamin B12 deficiency. These findings should be considered when
      balancing the risks and benefits of using these medications.

PMID- 24327037
TI  - Effect of CPAP on blood pressure in patients with obstructive sleep apnea and
      resistant hypertension: the HIPARCO randomized clinical trial.
AB  - IMPORTANCE: More than 70% of patients with resistant hypertension have
      obstructive sleep apnea (OSA). However, there is little evidence about the effect
      of continuous positive airway pressure (CPAP) treatment on blood pressure in
      patients with resistant hypertension. OBJECTIVE: To assess the effect of CPAP
      treatment on blood pressure values and nocturnal blood pressure patterns in
      patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS:
      Open-label, randomized, multicenter clinical trial of parallel groups with
      blinded end point design conducted in 24 teaching hospitals in Spain involving
      194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15
      or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS:
      CPAP or no therapy while maintaining usual blood pressure control medication.
      MAIN OUTCOMES AND MEASURES: The primary end point was the change in 24-hour mean
      blood pressure after 12 weeks. Secondary end points included changes in other
      blood pressure values and changes in nocturnal blood pressure patterns. Both
      intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS: A
      total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP
      (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8
      antihypertensive drugs were taken per patient. Baseline 24-hour mean blood
      pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and
      diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients
      displayed a dipper pattern (a decrease of at least 10% in the average nighttime
      blood pressure compared with the average daytime blood pressure). The percentage
      of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in
      blood pressure over the study period were compared between groups by ITT, the
      CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg
      [95% CI, 0.6 to 5.6]; P = .02) and 24-hour DBP (3.2 mm Hg [95% CI, 1.0 to 5.4]; P
      = .005), but not in 24-hour SBP (3.1 mm Hg [95% CI, -0.6 to 6.7]; P = .10)
      compared with the control group. Moreover, the percentage of patients displaying
      a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in
      the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio
      [OR], 2.4 [95% CI, 1.2 to 5.1]; P = .02). There was a significant positive
      correlation between hours of CPAP use and the decrease in 24-hour mean blood
      pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P =
      .005). CONCLUSIONS AND RELEVANCE: Among patients with OSA and resistant
      hypertension, CPAP treatment for 12 weeks compared with control resulted in a
      decrease in 24-hour mean and diastolic blood pressure and an improvement in the
      nocturnal blood pressure pattern. Further research is warranted to assess longer
      term health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00616265.

PMID- 24327039
TI  - Pruritus in the older patient: a clinical review.
AB  - IMPORTANCE: Pruritus is a common problem among elderly people and, when severe,
      causes as much discomfort as chronic pain. Little evidence supports pruritus
      treatment, limiting therapeutic possibilities and resulting in challenging
      management problems. OBJECTIVES: To present the evidence on the etiology,
      diagnosis, and treatment of pruritus in the elderly and, using the best available
      evidence, provide an approach for generalist physicians caring for older patients
      with pruritus. EVIDENCE REVIEW: PubMed and EMBASE databases were searched (1946
      August 2013).The Cochrane Database of Systematic Reviews and the Agency for
      Healthcare Research and Quality Systematic Review Data Repository were also
      searched from their inception to August 2013. References from retrieved articles
      were evaluated. FINDINGS: More than 50% of elderly patients have xerosis (dry
      skin). Xerosis treatment should be included in the initial therapy for pruritus
      in all elderly patients. Calcium channel blockers and hydrochlorothiazide are
      important causes of pruritic skin eruptions in older patients. Neuropathic
      pruritus is infrequently considered but may cause localized itching (especially
      in the genital area) and generalized truncal pruritus (especially in patients
      with diabetes mellitus). Certain skin conditions are more common in elderly
      patients, including scabies, bullous pemphigoid, transient acantholytic
      dermatosis, and mycosis fungoides, and should be considered in elderly patients
      with pruritus. CONCLUSIONS AND RELEVANCE: It is important to evaluate elderly
      patients for dermatological, systemic, and neurological etiologies of itch. A
      simple-to-apply diagnostic and therapeutic algorithm can be used. Xerosis, drug
      reactions, and neuropathy should be considered when evaluating pruritus.

PMID- 24327040
TI  - Differences in breast cancer survival by race.

PMID- 24327041
TI  - Therapy for posttraumatic stress and alcohol dependence.

PMID- 24327042
TI  - Differences in breast cancer survival by race--reply.

PMID- 24327043
TI  - Therapy for posttraumatic stress and alcohol dependence--reply.

PMID- 24327044
TI  - Drug postmarketing studies.

PMID- 24327045
TI  - Drug postmarketing studies--reply.

PMID- 24327048
TI  - Metabolism in cancer.

PMID- 24327049
TI  - JAMA patient page. Valley fever (coccidioidomycosis).

PMID- 24327050
TI  - Mind the gap: the transition to hospital consultant.
AB  - BACKGROUND: Thesis defended on the 19th of December 2012 at the faculty of
      Medicine of the VU University Amsterdam. Promotors: Professor Fedde Scheele MD,
      PhD, (VUmc Amsterdam) and Professor Albert Scherpbier MD, PhD (University of
      Maastricht). Copromotors: Pim Teunissen, MD, PhD (University of Maastricht) and
      Carl Siegert MD, PhD (St. Lucas Andreas Hospital, Amsterdam).

PMID- 24327051
TI  - The cyclic AMP response element-binding protein (CREB) mediates smooth muscle
      cell proliferation in response to angiotensin II.
AB  - The cAMP response element-binding protein (CREB) is a transcription factor that
      mediates the cellular response to metabolic and mitogenic signals. Whether CREB
      contributes to vascular function has received little attention, especially in
      relation to the processes associated with atherosclerotic disease progression and
      restenosis. This study examined the involvement of CREB in the mitogenic actions
      of angiotensin II (AngII), a growth factor that promotes neointimal hyperplasia
      in response to vascular injury. Treatments were performed on quiescent vascular
      smooth muscle cells (VSMCs) obtained from a porcine explant model. Organ culture
      was performed on porcine hearts subjected to angioplasty ex vivo. Stimulation of
      VSMCs with AngII resulted in transient CREB phosphorylation. Proliferation of
      smooth muscle cells in response to AngII was reduced by 90 % after infection with
      adenovirus expressing dominant-negative killer CREB (kCREB) mutant. Likewise,
      expression of kCREB prevented angioplasty-induced neointimal hyperplasia. AngII
      induced CREB phosphorylation was independent of cAMP activation. Examination of
      putative CREB kinases revealed that MSK was responsible for phosphorylating CREB.
      In addition, inhibition of PKC revealed that this kinase operates upstream and
      activates MSK. These results indicate that activation of CREB via PKC and MSK is
      essential for SMC proliferation in response to AngII. 

PMID- 24327052
TI  - Long-term potentiation of perforant pathway-dentate gyrus synapse in freely
      behaving mice.
AB  - Studies of long-term potentiation of synaptic efficacy, an activity-dependent
      synaptic phenomenon having properties that make it attractive as a potential
      cellular mechanism underlying learning and information storage, have long been
      used to elucidate the physiology of various neuronal circuits in the hippocampus,
      amygdala, and other limbic and cortical structures. With this in mind, transgenic
      mouse models of neurological diseases represent useful platforms to conduct long
      term potentiation (LTP) studies to develop a greater understanding of the role of
      genes in normal and abnormal synaptic communication in neuronal networks involved
      in learning, emotion and information processing. This article describes
      methodologies for reliably inducing LTP in the freely behaving mouse. These
      methodologies can be used in studies of transgenic and knockout freely behaving
      mouse models of neurodegenerative diseases.

PMID- 24327053
TI  - 5d iridium oxide as a material for spin-current detection.
AB  - Devices based on pure spin currents have been attracting increasing attention as
      key ingredients for low-dissipation electronics. To integrate such spintronics
      devices into charge-based technologies, electric detection of spin currents is
      essential. The inverse spin Hall effect converts a spin current into an electric
      voltage through spin-orbit coupling. Noble metals such as Pt and Pd, and also Cu
      based alloys, have been regarded as potential materials for a spin-current
      injector, owing to the large direct spin Hall effect. Their spin Hall resistivity
      rhoSH, representing the performance as a detector, is not large enough, however,
      due mainly because of their low charge resistivity. Here we report that a binary
      5d transition metal oxide, iridium oxide, overcomes the limitations encountered
      in noble metals and Cu-based alloys and shows a very large rhoSH~38 MUOmega cm at
      room temperature.

PMID- 24327054
TI  - Occupational risk factors for chronic respiratory disease in a New Zealand
      population using lifetime occupational history.
AB  - OBJECTIVES: To investigate associations between respiratory disease and
      occupational exposures in a New Zealand urban population, the Wellington
      Respiratory Survey. METHODS: Multiple regression analyses in a population sample
      of 1017 individuals aged 25 to 74 years with spirometry and questionnaire
      information, including a lifetime occupational history. RESULTS: Chronic
      bronchitis symptoms were associated with self-reported exposure to hairdressing,
      paint manufacturing, insecticides, welding, detergents and with ALOHA Job
      Exposure Matrix-assessed gases/fumes exposure. The strongest association was for
      hairdressing (odds ratio 6.91; 95% confidence interval: 2.02 to 23.70).
      Cumulative exposure to mineral dust and gases/fumes was associated with higher
      FEV1% (forced expiratory volume in the first second of expiration) predicted.
      Analyses were limited by relatively small numbers of cases. CONCLUSIONS:
      Increased risks of objectively defined respiratory disease, which have been
      previously documented, were not seen. Nevertheless, the study suggested increased
      risk of respiratory symptoms with various occupational exposures as well as
      likely healthy worker effect.

PMID- 24327055
TI  - Relationship between welding fume concentration and systemic inflammation after
      controlled exposure of human subjects with welding fumes from metal inert gas
      brazing of zinc-coated materials.
AB  - OBJECTIVES: It has been shown that exposure of subjects to emissions from a metal
      inert gas (MIG) brazing process of zinc-coated material led to an increase of
      high-sensitivity C-reactive protein (hsCRP) in the blood. In this study, the no
      observed-effect level (NOEL) for such emissions was assessed. METHODS: Twelve
      healthy subjects were exposed for 6 hours to different concentrations of MIG
      brazing fumes under controlled conditions. High-sensitivity C-reactive protein
      was measured in the blood. RESULTS: For welding fumes containing 1.20 and 1.50 mg
      m zinc, high-sensitivity C-reactive protein was increased the day after exposure.
      For 0.90 mg m zinc, no increase was detected. CONCLUSIONS: These data indicate
      that the no-observed-effect level for emissions from a MIG brazing process of
      zinc-coated material in respect to systemic inflammation is found for welding
      fumes with zinc concentrations between 0.90 and 1.20 mg m.

PMID- 24327056
TI  - What is the point of doctors?

PMID- 24327057
TI  - Hospital trusts will have to cut activity when integration fund comes into
      effect, meeting is told.

PMID- 24327058
TI  - MicroRNA-499 rs3746444 polymorphism and autoimmune diseases risk: a meta
      analysis.
AB  - BACKGROUND AND OBJECTIVE: MicroRNA (miR)-499 rs3746444 polymorphisms may
      participate in the pathogenesis of autoimmune diseases, but the results remain
      conflicting. We further investigated this association using a meta-analysis.
      METHODS: We conducted a retrieval of studies and obtained the eligible studies if
      they met inclusion criteria. Two researchers independently extracted the data
      from original articles. The genotype frequencies were analysed using Stata
      software. RESULTS: We finally archived six eligible studies that included 1,118
      cases and 1,673 controls. After pooling the data, the results indicated that
      homozygote TT had an overall association with autoimmune diseases (TC + CC vs.
      TT: odds ratio [OR] 1.31, 95% CI 1.11-1.55, p = 0.001). The allele C, genotype TC
      and CC, may be associated with rheumatoid arthritis (RA) risks in Mediterranean
      populations (C vs. T: OR 2. 00, 95% CI 1.37-2.91, p < 0.001; TC vs. CC + TT: OR
      1.76, 95% CI 1.27-2.44; p = 0.001; CC vs. TC + TT: OR 2.31, 95% CI 1.24-4.27, p =
      0.008; CC vs. TT: OR 2.92, 95% CI 1.59-5.37, p = 0.001; TC vs. TT: OR 1.98, 95%
      CI 1.42-2.77). The genotype TT may decrease the risk of RA in Mediterranean
      populations (TC + CC vs. TT: OR 2.15, 95% CI 1.57-2.94, p < 0.001) rather than in
      East Asians. CONCLUSIONS: This study suggested that miR-499 polymorphisms were
      associated with a significantly increased risk of RA in Mediterranean
      populations.

PMID- 24327059
TI  - Quantifying surgical access in eyebrow craniotomy with and without orbital bar
      removal: cadaver and surgical phantom studies.
AB  - BACKGROUND: Eyebrow craniotomy is a recently described minimally invasive
      approach for tackling primarily pathology of the anterior skull base. The removal
      of the orbital bar may further expand the surgical corridor of this exposure, but
      the extent of benefit is poorly quantified. We assessed the effect of orbital bar
      removal with regards to surgical access in the eyebrow craniotomy using classic
      morphometric measurements in cadaver heads. Using surgical phantoms and
      neuronavigation, we also measured the 'working volume', a new parameter for
      characterising the volume of surgical access in these approaches. METHODS:
      Silicon injected cadaver heads (n = 5) were used for morphometric analysis of the
      eyebrow craniotomy with and without orbital bar removal. Working depths and
      'working areas' of surgical access were measured as defined by key anatomical
      landmarks. The eyebrow craniotomy with or without orbital bar removal was also
      simulated using surgical phantoms (n = 3, 90-120 points per trial), calibrated
      against a frameless neuronavigation system. Working volume was derived from
      reference coordinates recorded along the anatomical borders of the eyebrow
      craniotomy using the "alpha-shape algorithm" in R statistics. RESULTS: In cadaver
      heads, eyebrow craniotomy with removal of the orbital bar reduced the working
      depth to the ipsilateral anterior clinoid process (42 +/- 2 versus 33 +/- 3 mm; p
      < 0.05), but the working areas as defined by deep neurovascular and bony
      landmarks was statistically unchanged (total working areas of 418 +/- 80 cm(2)
      versus 334 +/- 48 cm(2); p = 0.4). In surgical phantom studies, however, working
      volume for the simulated eyebrow craniotomies was increased with orbital bar
      removal (16 +/- 1 cm(3) versus 21 +/- 1 cm(3); p < 0.01). CONCLUSIONS: In
      laboratory studies, orbital bar removal in eyebrow craniotomy provides a modest
      reduction in working depth and increase in the working volume. But this must be
      weighed up against the added morbidity of the procedure. Working volume, a newly
      developed parameter may provide a more meaningful endpoint for characterising the
      surgical access for different surgical approaches and it could be applied to
      other operative cases undertaken with frameless neuronavigation.

PMID- 24327060
TI  - The effect of the size of surface Pd island ensembles on electron transfer of
      adsorbed perchlorate ions on Au(111).
AB  - A progressive increase in the size of Pd ensembles on a mica-supported Au(111)
      single crystal surface can facilitate electron transfer of perchlorate ions at
      lower anodic potential in CV curves than pure Au(111) due to a strong ligand
      effect and Pd-Au neighbouring pairs at edge sites render a higher degree of
      electron transfer. 

PMID- 24327062
TI  - Linear neutral platinum-acetylide moiety: beyond the links.
AB  - In this feature article, brief highlights of research progress on the linear
      neutral platinum-acetylide moiety, trans-Pt(PR3)2(C=CR')2, are presented. Due to
      its unique characteristics such as the well-defined linear geometry, synthetic
      accessibility, and intriguing photoproperties, this type of platinum-acetylide
      moiety has been extensively investigated in many respects from supramolecular
      chemistry to materials science during the past two decades. However, compared
      with the extensively studied charged platinum-acetylide complexes, the linear
      neutral platinum-acetylide moiety has been less reviewed. Based upon our recent
      progress in platinum chemistry, we provide herein a brief review on the linear
      neutral platinum-acetylide building block. This feature article will focus on its
      role as a linkage building block, but beyond the links. Three aspects including
      complex architectures composed of platinum-acetylide links, platinum-acetylide
      bridged multichromophoric arrays, and supramolecular self-assembly of platinum
      acetylide building blocks are discussed.

PMID- 24327061
TI  - Multimodal evaluation of macular function in age-related macular degeneration.
AB  - OBJECTIVE: To evaluate macular function using multimodality in eyes with age
      related macular degeneration (AMD) at various stages. METHODS: Macular function
      in 20 control eyes (20 subjects), 17 eyes (17 patients) with large drusen, 18
      eyes (18 patients) with drusenoid pigment epithelial detachment (PED), and 19
      eyes (19 patients) with neovascular AMD was examined using a Landolt chart for
      visual acuity; retinal sensitivity was measured by microperimetry; and focal
      macular electroretinography (fmERG) was performed. In all of these eyes, retinal
      morphology was examined using optical coherence tomography. RESULTS: Eyes with
      neovascular AMD showed morphologic changes in the neurosensory retina as well as
      marked deterioration of macular function in all parameters measured with a
      Landolt chart, fmERG, and microperimetry. Eyes with large drusen showed only
      minimal morphologic changes in the neurosensory retina. In this large drusen
      group, although retinal sensitivity at the central point was significantly
      decreased (P = 0.0063), the other parameters of macular function were well
      preserved. In eyes with drusenoid PED, the structure of the neurosensory retina
      was well preserved, while the foveal thickness was significantly increased (P =
      0.013). The macular function of these eyes was significantly deteriorated, with
      the VA, amplitude of the a-wave and b-wave, and retinal sensitivity being
      markedly decreased. In addition, the area of PED correlated with the latency of
      the a-wave and b-wave and with the retinal sensitivity within the central 4
      degrees  or 8 degrees  region. CONCLUSION: Multimodal evaluation demonstrated a
      significant decrease in macular function in drusenoid PED and in neovascular AMD.

PMID- 24327063
TI  - A beta unfolding model for continuous bounded responses.
AB  - An unfolding model for continuous bounded responses is proposed, derived both
      from a hypothetical interpolation response mechanism and from the hypothesis of
      two opposite sources of item refusal being collapsed. These two sources of
      refusal are made explicit in a three-component Dirichlet response model and then
      collapsed to obtain a (two-component) beta response model. The two natural
      parameters of the beta are interpreted as acceptance and refusal parameters and
      expressed as functions of person-item distances on a latent continuum. The
      potentially bimodal shape of the beta is exploited to model chaotic response
      choices among ambivalent subjects. 

PMID- 24327064
TI  - Bayesian inferences of latent class models with an unknown number of classes.
AB  - This paper focuses on analyzing data collected in situations where investigators
      use multiple discrete indicators as surrogates, for example, a set of
      questionnaires. A very flexible latent class model is used for analysis. We
      propose a Bayesian framework to perform the joint estimation of the number of
      latent classes and model parameters. The proposed approach applies the reversible
      jump Markov chain Monte Carlo to analyze finite mixtures of multivariate
      multinomial distributions. In the paper, we also develop a procedure for the
      unique labeling of the classes. We have carried out a detailed sensitivity
      analysis for various hyperparameter specifications, which leads us to make
      standard default recommendations for the choice of priors. The usefulness of the
      proposed method is demonstrated through computer simulations and a study on
      subtypes of schizophrenia using the Positive and Negative Syndrome Scale (PANSS).

PMID- 24327065
TI  - Hierarchical Bayesian Modeling for Test Theory Without an Answer Key.
AB  - Cultural Consensus Theory (CCT) models have been applied extensively across
      research domains in the social and behavioral sciences in order to explore shared
      knowledge and beliefs. CCT models operate on response data, in which the answer
      key is latent. The current paper develops methods to enhance the application of
      these models by developing the appropriate specifications for hierarchical
      Bayesian inference. A primary contribution is the methodology for integrating the
      use of covariates into CCT models. More specifically, both person- and item
      related parameters are introduced as random effects that can respectively account
      for patterns of inter-individual and inter-item variability. 

PMID- 24327066
TI  - Constrained Stochastic Extended Redundancy Analysis.
AB  - We devise a new statistical methodology called constrained stochastic extended
      redundancy analysis (CSERA) to examine the comparative impact of various
      conceptual factors, or drivers, as well as the specific predictor variables that
      contribute to each driver on designated dependent variable(s). The technical
      details of the proposed methodology, the maximum likelihood estimation algorithm,
      and model selection heuristics are discussed. A sports marketing consumer
      psychology application is provided in a Major League Baseball (MLB) context where
      the effects of six conceptual drivers of game attendance and their defining
      predictor variables are estimated. Results compare favorably to those obtained
      using traditional extended redundancy analysis (ERA). 

PMID- 24327067
TI  - Empirical Correction to the Likelihood Ratio Statistic for Structural Equation
      Modeling with Many Variables.
AB  - Survey data typically contain many variables. Structural equation modeling (SEM)
      is commonly used in analyzing such data. The most widely used statistic for
      evaluating the adequacy of a SEM model is T ML, a slight modification to the
      likelihood ratio statistic. Under normality assumption, T ML approximately
      follows a chi-square distribution when the number of observations (N) is large
      and the number of items or variables (p) is small. However, in practice, p can be
      rather large while N is always limited due to not having enough participants.
      Even with a relatively large N, empirical results show that T ML rejects the
      correct model too often when p is not too small. Various corrections to T ML have
      been proposed, but they are mostly heuristic. Following the principle of the
      Bartlett correction, this paper proposes an empirical approach to correct T ML so
      that the mean of the resulting statistic approximately equals the degrees of
      freedom of the nominal chi-square distribution. Results show that empirically
      corrected statistics follow the nominal chi-square distribution much more closely
      than previously proposed corrections to T ML, and they control type I errors
      reasonably well whenever N >= max(50,2p). The formulations of the empirically
      corrected statistics are further used to predict type I errors of T ML as
      reported in the literature, and they perform well.

PMID- 24327068
TI  - A Rate Function Approach to Computerized Adaptive Testing for Cognitive
      Diagnosis.
AB  - Computerized adaptive testing (CAT) is a sequential experiment design scheme that
      tailors the selection of experiments to each subject. Such a scheme measures
      subjects' attributes (unknown parameters) more accurately than the regular
      prefixed design. In this paper, we consider CAT for diagnostic classification
      models, for which attribute estimation corresponds to a classification problem.
      After a review of existing methods, we propose an alternative criterion based on
      the asymptotic decay rate of the misclassification probabilities. The new
      criterion is then developed into new CAT algorithms, which are shown to achieve
      the asymptotically optimal misclassification rate. Simulation studies are
      conducted to compare the new approach with existing methods, demonstrating its
      effectiveness, even for moderate length tests. 

PMID- 24327071
TI  - DNA methylation-associated inactivation of TGFbeta-related genes, DRM/Gremlin,
      RUNX3, and HPP1 in human cancers.

PMID- 24327069
TI  - Synthetic cell division system: controlling equal vs. unequal divisions by
      design.
AB  - Cell division is one of the most fundamental and evolutionarily conserved
      biological processes. Here, we report a synthetic system where we can control by
      design equal vs. unequal divisions. We synthesized a micro-scale inverse
      amphipathic droplet of which division is triggered by the increase of surface to
      volume ratio. Using this system, we succeeded in selectively inducing equal vs.
      unequal divisions of the droplet cells by adjusting the temperature or the
      viscosity of the solvent outside the droplet cell accordingly. Our synthetic
      division system may provide a platform for further development to a system where
      intracellular contents of the parent droplet cell could be divided into various
      ratios between the two daughter droplet cells to control their functions and
      fates. 

PMID- 24327074
TI  - Electrochemical, spectroscopic and theoretical studies of a simple bifunctional
      cobalt corrole catalyst for oxygen evolution and hydrogen production.
AB  - Six cobalt and manganese corrole complexes were synthesized and examined as
      single-site catalysts for water splitting. The simple cobalt corrole
      [Co(tpfc)(py)2] (1, tpfc = 5,10,15-tris(pentafluorophenyl)corrole, py = pyridine)
      catalyzed both water oxidation and proton reduction efficiently. By coating
      complex 1 onto indium tin oxide (ITO) electrodes, the turnover frequency for
      electrocatalytic water oxidation was 0.20 s(-1) at 1.4 V (vs. Ag/AgCl, pH = 7),
      and it was 1010 s(-1) for proton reduction at -1.0 V (vs. Ag/AgCl, pH = 0.5). The
      stability of 1 for catalytic oxygen evolution and hydrogen production was
      evaluated by electrochemical, UV-vis and mass measurements, scanning electron
      microscope (SEM) and energy dispersive X-ray spectroscopy (EDX), which confirmed
      that 1 was the real molecular catalyst. Titration and UV-vis experiments showed
      that the pyridine group on Co dissociated at the beginning of catalysis, which
      was critical to subsequent activation of water. A proton-coupled electron
      transfer process was involved based on the pH dependence of the water oxidation
      reaction catalyzed by 1. As for manganese corroles 2-6, although their oxidizing
      powers were comparable to that of 1, they were not as stable as 1 and underwent
      decomposition at the electrode. Density functional theory (DFT) calculations
      indicated that water oxidation by 1 was feasible through a proposed catalytic
      cycle. The formation of an O-O bond was suggested to be the rate-determining
      step, and the calculated activation barrier of 18.1 kcal mol(-1) was in good
      agreement with that obtained from experiments.

PMID- 24327075
TI  - Development and validation of a rapid multiplex ELISA for pyrrolizidine alkaloids
      and their N-oxides in honey and feed.
AB  - Pyrrolizidine alkaloids (PAs) are a group of plant secondary metabolites with
      carcinogenic and hepatotoxic properties. When PA-producing plants contaminate
      crops, toxins can be transferred through the food chain and cause illness in
      humans and animals, most notably hepatic veno-occlusive disease. Honey has been
      identified as a direct risk of human exposure. The European Food Safety Authority
      has recently identified four groups of PAs that are of particular importance for
      food and feed: senecionine-type, lycopsamine-type, heliotrine-type and
      monocrotaline-type. Liquid or gas chromatography methods are currently used to
      detect PAs but there are no rapid screening assays available commercially.
      Therefore, the aim of this study was to develop a rapid multiplex ELISA test for
      the representatives of three groups of alkaloids (senecionine, lycopsamine and
      heliotrine types) that would be used as a risk-management tool for the screening
      of these toxic compounds in food and feed. The method was validated for honey and
      feed matrices and was demonstrated to have a detection capability less than 25
      MUg/kg for jacobine, lycopsamine, heliotrine and senecionine. The zinc reduction
      step introduced to the extraction procedure allows for the additional detection
      of the presence of N-oxides of PAs. This first multiplex immunoassay for PA
      detection with N-oxide reduction can be used for the simultaneous screening of 21
      samples for >12 PA analytes. Honey samples (n = 146) from various origins were
      analysed for PA determination. Six samples were determined to contain measurable
      PAs >25 MUg/kg by ELISA which correlated to >10 MUg/kg by LC-MS/MS. 

PMID- 24327076
TI  - Microbial communities analysis assessed by pyrosequencing--a new approach applied
      to conservation state studies of mural paintings.
AB  - The knowledge about the microbial communities present in mural paintings is of
      utmost importance to develop effective conservation and mitigation strategies.
      The present paper describes a methodological approach for the detailed
      characterisation of microorganisms thriving in mural paintings by combining
      culture-dependent methods that allow the identification of microorganisms capable
      of growing in the laboratory conditions and to obtain high cell densities for
      further studies, and culture independent methods, such as denaturing gradient gel
      electrophoresis (DGGE) and pyrosequencing. The coupled use of culture-dependent
      methods and DGGE does not give enough information to investigate the diversity
      and abundance of microorganisms present in wall paintings. Pyrosequencing, a
      novel molecular technique, used here for the first time in this area of research,
      allowed the identification of a large number of microorganisms, confirming some
      already identified by the cultivation-dependent methods such as fungi of the
      genera Penicillium and Cladosporium, but also providing a great contribution in
      the identification of several genera and species, not previously identified in
      these artworks, giving also a detailed overview of contaminants which was not
      possible with the other approaches. The results obtained on several mural
      painting samples show a strong relationship between the most deteriorated areas
      of the paintings and higher microbial contamination. 

PMID- 24327077
TI  - Assessing the multisite binding properties of multiple sources of dissolved
      organic matter at nanomolar copper concentrations using piecewise linear
      regression and parallel factor analysis of fluorescence quenching.
AB  - This study reports on the development and application of a piecewise linear model
      for the determination of copper-binding parameters at concentrations in the
      nanomolar range using fluorescence quenching. L-Tyrosine, Suwannee River natural
      organic matter, and two leaf leachates with similar fluorescence signatures were
      used as test compounds, and results were compared with those of the standard Ryan
      Weber model. The piecewise model was also applied to and compared with data from
      an earlier study. Parallel factor analysis (PARAFAC) was used to identify three
      to five independent fluorophores in each test compound, and copper-binding
      parameters were estimated for one to three binding sites for each fluorophore.
      The binding properties of similar and different fluorophores were also compared.
      The conditional binding strengths (log K') estimated using the piecewise approach
      were similar to those obtained using the Ryan-Weber approach (p > 0.05); however,
      the piecewise linear model provided superior results compared to models based on
      the Ryan-Weber equation in several ways, including (1) capable of distinguishing
      more binding sites for a single fluorophore, (2) capable of extracting binding
      parameters at environmentally relevant, nanomolar concentrations of copper, where
      fluorescence changes are often observed as enhancement, (3) greater precision
      over repeated titrations, and (4) no severe underestimation of complexing
      capacities. Finally, the copper-binding properties of PARAFAC components with
      similar optical signatures were found to be similar, both in sources with
      dramatically different and similar total fluorescence signatures. 

PMID- 24327078
TI  - Simultaneous high-performance liquid chromatography-tandem mass spectrometry
      (HPLC-MS-MS) analysis of cyanide and thiocyanate from swine plasma.
AB  - An analytical procedure for the simultaneous determination of cyanide and
      thiocyanate in swine plasma was developed and validated. Cyanide and thiocyanate
      were simultaneously analyzed by high-performance liquid chromatography tandem
      mass spectrometry in negative ionization mode after rapid and simple sample
      preparation. Isotopically labeled internal standards, Na(13)C(15)N and
      NaS(13)C(15)N, were mixed with swine plasma (spiked and nonspiked), proteins were
      precipitated with acetone, the samples were centrifuged, and the supernatant was
      removed and dried. The dried samples were reconstituted in 10 mM ammonium
      formate. Cyanide was reacted with naphthalene-2,3-dicarboxaldehyde and taurine to
      form N-substituted 1-cyano[f]benzoisoindole, while thiocyanate was chemically
      modified with monobromobimane to form an SCN-bimane product. The method produced
      dynamic ranges of 0.1-50 and 0.2-50 MUM for cyanide and thiocyanate,
      respectively, with limits of detection of 10 nM for cyanide and 50 nM for
      thiocyanate. For quality control standards, the precision, as measured by percent
      relative standard deviation, was below 8 %, and the accuracy was within +/-10 %
      of the nominal concentration. Following validation, the analytical procedure
      successfully detected cyanide and thiocyanate simultaneously from the plasma of
      cyanide-exposed swine. 

PMID- 24327079
TI  - The neutrophil-lymphocyte ratio is not enough to describe inflammatory condition.

PMID- 24327080
TI  - Quantitative study on endoscopic endonasal approach to the posterior sino-orbito
      cranial interface: implications and clinical considerations.
AB  - The posterior sino-orbito-cranial interface is a critical area in the skull base
      since it represents a gateway to deeper vital regions. Quantification of the
      surgical freedom for any given point/area is an objective method for comparing in
      a reproducible way different surgical approaches. Three freshly injected cadaver
      heads (six sides) were dissected under the magnetic navigation control system.
      The surgical freedom (SF) and the angle of attack of fixed target points were
      determined from the ipsilateral nasal fossa, from the contralateral nasal fossa
      (after posterior septectomy), and after an anteromedial maxillotomy (according to
      the Denker procedure). The mean pre-operative SF value resulted to be 403.07 +/-
      102.73 mm(2) for the ipsilateral nostril, increasing by 126.97 % for the
      binostril approach, by 118.45 % for the monolateral nostril approach after
      anteromedial maxillotomy, and by 310.48 % for the binostril approach after
      bilateral anteromedial maxillotomy. Laterally extended lesions require an
      anteromedial maxillotomy, while more medially located lesions can be managed by
      means of a posterior septectomy. When addressing the posterior sino-orbito
      cranial interface, the transnasal binostril approach and anteromedial maxillotomy
      both increase the SF. The choice between them depends on exact position,
      relationship and clinical behaviour of the lesion to treat.

PMID- 24327081
TI  - Lower cranial nerves function after surgical treatment of Fisch Class C and D
      tympanojugular paragangliomas.
AB  - The aim of this study was to report the postoperative lower cranial nerves (LCNs)
      function in patients undergoing surgery for tympanojugular paraganglioma (TJP)
      and to evaluate risk factors for postoperative LCN dysfunction. A retrospective
      case review of 122 patients having Fisch class C or D TJP, surgically treated
      from 1988 to 2012, was performed. The follow-up of the series ranged from 12 to
      156 months (mean, 39.4 +/- 32.6 months). The infratemporal type A approach was
      the most common surgical procedure. Gross total tumor removal was achieved in 86%
      of cases. Seventy-two percent of the 54 patients with preoperative LCN deficit
      had intracranial tumor extension. Intraoperatively, LCNs had to be sacrificed in
      63 cases (51.6%) due to tumor infiltration. Sixty-six patients (54.09%) developed
      a new deficit of one or more of the LCNs. Of those patients who developed new LCN
      deficits, 23 of them had intradural extension. Postoperative follow-up of at
      least 1 year showed that the LCN most commonly affected was the CN IX (50%).
      Logistic regression analysis showed that intracranial transdural tumor extension
      was correlated with the higher risk of LCN sacrifice (p < 0.05). Despite the
      advances in skull base surgery, new postoperative LCN deficits still represent a
      challenge. The morbidity associated with resection of the LCNs is dependent on
      the tumor's size and intradural tumor extension. Though no recovery of LCN
      deficits may be expected, on long-term follow-up, patients usually compensate
      well for their LCNs loss.

PMID- 24327083
TI  - Unusual chest pain syndromes caused by implanted cardiac device leads: a case
      series.
AB  - Chest pain can occur after cardiac device lead placement through various
      mechanisms. Commonly, this is secondary to perforation. We present four cases of
      unusual chest pain syndromes secondary to device leads with normal function and
      position without evidence of typical complications. The possible etiologies and
      management considerations for these cases are discussed. 

PMID- 24327084
TI  - Thrombocytopenia in children with vivax malaria: a study from north India.
AB  - OBJECTIVES: To study incidence, severity and clinical significance of
      thrombocytopenia and to study recovery pattern of platelet counts in children
      with vivax malaria. METHODS: This was a retrospective hospital based descriptive
      case series. Cases of confirmed vivax malaria were studied and their Total
      Platelet Counts (TPC) evaluated daily till recovery and again after 1 wk on
      follow up visit. RESULTS: In this study out of 39 children of confirmed vivax
      malaria 22 had thrombocytopenia, having mean platelet count 48 * 10(9)/L on
      admission which showed a very quick recovery on treatment and by day 3 of
      treatment it rose to 126.5 * 10(9)/L without platelet transfusion. In untreated
      cases the lowest platelet counts was observed on day 5-6 and on treatment,
      platelet counts returned to normal without any platelet transfusion by 9th day.
      Even among children there are variations in different age groups and younger ones
      show more quicker recovery than older peers. CONCLUSIONS: Vivax malaria is
      associated with transient thrombocytopenia which does not lead to significant
      bleeding in children.

PMID- 24327085
TI  - Acute hemorrhagic edema of infancy.
AB  - The authors report an 11-mo-old child presenting with acute onset appearance of
      large, erythematous, palpable purpuric lesions involving face, extremities and
      trunk. Skin biopsy from the margin of the lesions showed leukocytoclastic
      vasculitis suggesting a diagnosis of acute hemorrhagic edema of infancy. This
      rare type of cutaneous vasculitis, despite its grave presentation is a benign
      condition with self-limiting course. 

PMID- 24327086
TI  - The passive leg raise test to predict fluid responsiveness in children-
      preliminary observations.
AB  - OBJECTIVE: To assess whether the passive leg raising (PLR) test can predict fluid
      responsiveness in pediatric patients. METHODS: This was a prospective
      observational study in a tertiary care pediatric center. Hemodynamic parameters
      including heart rate, stroke volume and cardiac output were assessed at baseline,
      after passive leg raising (PLR), at second baseline, and after volume loading (10
      mL/kg normal saline in 10 min). Cutoff values of 7.5 and 10 % increase in cardiac
      index (CI) with passive leg raising were explored as predictors of volume loading
      response. RESULTS: Overall, the changes in CI with passive leg raising varied
      widely and was a poor predictor of response to volume loading in children under 5
      years of age. Of 40 patients, 23 had greater than 10 % increase in CI with PLR
      which predicted fluid responsiveness with a sensitivity of 94 % (95 % confidence
      interval 71,100) and specificity of 26 % (95 % confidence interval 10,48).
      Sensitivity was higher (100 % vs. 91 %) and specificity similar (27 % vs. 25 %)
      in predicting CI for those over 5 as compared to under 5 y, respectively. In
      patients over 5 y, simple linear regression revealed a positive correlation (R(2)
      = 21) while R(2) values were much lower (0-0.07) for those under 5 y.
      CONCLUSIONS: Cardiac index changes after PLR varies widely in children and may be
      a poor predictor to volume loading in children under 5-y-old. However, in those
      over 5 y, PLR may be helpful in predicting fluid responsiveness in pediatric
      patients.

PMID- 24327087
TI  - Opioid signaling in mast cells regulates injury responses associated with
      heterotopic ossification.
AB  - INTRODUCTION: Previous studies found that neuron specific enolase promoter (Nse
      BMP4) transgenic mice have increased expression of the nociceptive mediator,
      substance P and exaggerated local injury responses associated with heterotopic
      ossification (HO). It is of interest great to know the pain responses in these
      mice and how the opioid signaling is involved in the downstream events such as
      mast cell (MC) activation. MATERIALS AND METHODS: This study utilized a
      transgenic mouse model of HO in which BMP4 is expressed under the control of the
      Nse-BMP4. The tactile sensitivity and the cold sensitivity of the mice were
      measured in a classic inflammatory pain model (carrageenan solution injected into
      the plantar surface of the left hind paw). The MC activation and the expression
      profiles of different components in the opioid signaling were demonstrated
      through routine histology and immunohistochemistry and Western blotting, in the
      superficial and deep muscle injury models. RESULTS: We found that the pain
      responses in these mice were paradoxically attenuated or unchanged, and we also
      found increased expression of both Methionine Enkephalin (Met-Enk), and the MU
      opioid receptor (MOR). Met-Enk and MOR both co-localized within activated MCs in
      limb tissues. Further, Nse-BMP4;MOR(-/-) double mutant mice showed attenuated MC
      activation and had a significant reduction in HO formation in response to
      injuries. CONCLUSIONS: These observations suggest that opioid signaling may play
      a key role in MC activation and the downstream inflammatory responses associated
      with HO. In addition to providing insight into the role of MC activation and
      associated injury responses in HO, these findings suggest opioid signaling as a
      potential therapeutic target in HO and possibly others disorders involving MC
      activation.

PMID- 24327088
TI  - Infection through structured polymicrobial Gardnerella biofilms (StPM-GB).
AB  - BACKGROUND: We analysed data on bacterial vaginosis (BV) contradicting the
      paradigm of mono-infection. METHODOLOGY: Tissues and epithelial cells of vagina,
      uterus, fallopian tubes and perianal region were investigated using fluorescence
      in situ hybridization (FISH) in women with BV and controls. RESULTS: Healthy
      vagina was free of biofilms. Prolific structured polymicrobial (StPM) Gardnerella
      dominated biofilm characterised BV. The intact StPM-Gardnerella-biofilm enveloped
      desquamated vaginal/prepuce epithelial cells and was secreted with urine and
      sperma. The disease involved both genders and occurred in pairs. Children born to
      women with BV were negative. Monotherapy with metronidazole, moxifloxacin or
      local antiseptics suppressed but often did not eradicate StPM-Gardnerella
      biofilms. There was no BV without Gardnerella, but Gardnerella was not BV.
      Outside of StPM-biofilm, Gardnerella was also found in a subset of children and
      healthy adults, but was dispersed, temporal and did not transform into StPM
      Gardnerella-biofilm. CONCLUSIONS: StPM-Gardnerella-biofilm is an infectious
      subject. The assembly of single players to StPM-Gardnerella-biofilm is a not
      trivial every day process, but probably an evolutionary event with a long history
      of growth, propagation and selection for viability and ability to reshape the
      environment. The evolutionary memory is cemented in the structural
      differentiation of StPM-Gardnerella-biofilms and imparts them to resist previous
      and emerging challenges.

PMID- 24327089
TI  - Genomic characterization and integrative properties of phiSMA6 and phiSMA7, two
      novel filamentous bacteriophages of Stenotrophomonas maltophilia.
AB  - Two novel filamentous phages, phiSMA6 and phiSMA7, were isolated from
      Stenotrophomonas maltophilia environmental strain Khak84. We identified and
      annotated 11 potential open reading frames in each phage. While the overall
      layout of the functional gene groups of both phages was similar to that of the
      known filamentous phages, they differed from them in their molecular structure.
      The genome of phiSMA6 is a mosaic that evolved by acquiring genes from at least
      three different filamentous S. maltophilia phages and one Xanthomonas campestris
      phage related to Cf1. In the phiSMA6 genome, a gene similar to the bacterial gene
      encoding the mating pair formation protein trbP was also found. We showed that
      phiSMA6 possesses lysogenic properties and upon induction produces high-titer
      lysates. The genome of phiSMA7 possesses a unique structure and was found to be
      closely related to a prophage present in the chromosome of the completely
      sequenced S. maltophilia clinical strain D457. We suggest that the other three
      filamentous phages of S. maltophilia described previously also have the capacity
      to integrate into the genome of their bacterial host.

PMID- 24327090
TI  - Lamium amplexicaule (Lamiaceae): a weed reservoir for tomato yellow leaf curl
      virus (TYLCV) in Korea.
AB  - After the first identification of tomato yellow leaf curl virus (TYLCV) in the
      southern part of Korea in 2008, TYLCV has rapidly spread to tomato farms in most
      regions of Korea. From 2008 to 2010, a survey of natural weed hosts that could be
      reservoirs of TYLCV was performed in major tomato production areas of Korea.
      About 530 samples were collected and identified as belonging to 25 species from
      11 families. PCR and Southern hybridization were used to detect TYLCV in samples,
      and replicating forms of TYLCV DNA were detected in three species (Achyranthes
      bidentata, Lamium amplexicaule, and Veronica persica) by Southern hybridization.
      TYLCV transmission mediated by Bemisia tabaci from TYLCV-infected tomato plants
      to L. amplexicaule was confirmed, and TYLCV-infected L. amplexicaule showed
      symptoms such as yellowing, stunting, and leaf curling. TYLCV from infected L.
      amplexicaule was also transmitted to healthy tomato and L. amplexicaule plants by
      B. tabaci. The rate of infection of L. amplexicaule by TYLCV was similar to that
      of tomato. This report is the first to show that L. amplexicaule is a reservoir
      weed host for TYLCV.

PMID- 24327091
TI  - Rubella virus genotype 1G and echovirus 9 as etiologic agents of exanthematous
      diseases in Brazil: insights from phylogenetic analysis.
AB  - The aim of the present study was to identify the rubella virus (RV) and
      enterovirus (EV) genotypes detected during the Epidemiological Surveillance on
      Exanthematic Febrile Diseases (VIGIFEX) study and to perform phylogenetic
      analysis. Ten RV- and four EV-positive oropharyngeal samples isolated from cell
      culture were subjected to RT-PCR and sequencing. Genotype 1G and echovirus 9 (E
      9) was identified in RV- and EV-positive samples, respectively. The RV 1G
      genotype has been persisting in Brazil since 2000-2001. No evidence of E-9 being
      involved in exanthematic illness in Brazil has been reported previously.
      Differential laboratory diagnosis is essential for management of rash and fever
      disease.

PMID- 24327092
TI  - First survey of the occurrence of duck enteritis virus (DEV) in free-ranging
      Polish water birds.
AB  - Duck plague (DP) caused by anatid herpesvirus 1, also called duck enteritis virus
      (DEV), presents one of the most important concerns in mass waterfowl production.
      Apart from geese and ducks, free-ranging water birds are the most notorious
      infection carriers. The epidemiology of DEV in Western Europe remains unknown.
      Therefore, it was reasonable to conduct a study on its occurrence using modern
      but simple real-time loop-mediated isothermal amplification (LAMP). Analysis of
      132 field isolates showed the presence of DEV in 96 birds (72.7 %), and it was
      found predominantly in wild ducks (Anas platyrhynchos) and mute swans (Cygnus
      olor). This virus was also found in graylag geese (Anser anser), tundra bean
      geese (Anser fabalis), and grey herons (Ardea cinerea). The results were recorded
      as green colour of positive samples, fluorescence under ultraviolet light, and
      florescent curves in a real-time PCR system. This study indicates the high
      prevalence of DEV among free-ranging water birds in Poland and the possible
      transmission to other birds settling in the water environment. This is the first
      report of DEV detection among free-ranging water birds in Poland.

PMID- 24327093
TI  - Molecular characterization of a novel victorivirus from the entomopathogenic
      fungus Beauveria bassiana.
AB  - New Zealand isolates of the entomopathogenic fungus Beauveria were examined for
      the presence of dsRNAs and virus-like particles. Seven out of nine isolates
      contained one or more high-molecular-weight dsRNAs and all seven contained
      isometric virus particles ranging in size from 30 to 50 nm. B. bassiana isolate
      ICMP#6887 contained a single dsRNA band of ~6 kb and isometric virus-like
      particles of ~50 nm in diameter. Sequencing revealed that the virus from
      ICMP#6887 had a genome of 5,327 nt with two overlapping ORFs coding for a
      putative coat protein (CP) and an RNA-dependent RNA-polymerase (RdRp). The
      sequence showed a highest CP identity of 58.3 % to Tolypocladium cylindrosporum
      virus 1 (TcV1) and a highest RdRp identity of 48.8 % to Sphaeropsis sapinea RNA
      virus 1 (SsRV1). Since both TcV1 and SsRV1 belong to the genus Victorivirus, the
      new virus from B. bassiana ICMP#6887 was tentatively assigned the name Beauveria
      bassiana victorivirus 1 (BbVV1-6887).

PMID- 24327094
TI  - The molecular biology of nairoviruses, an emerging group of tick-borne
      arboviruses.
AB  - The nairoviruses are a rapidly emerging group of tick-borne bunyaviruses that
      includes pathogens of humans (Crimean-Congo hemorrhagic fever virus [CCHFV]) and
      livestock (Nairobi sheep disease virus [NSDV], also known as Ganjam virus), as
      well as a large number of viruses for which the normal vertebrate host has not
      been established. Studies on this group of viruses have been fairly limited, not
      least because CCHFV is a BSL4 human pathogen, restricting the number of labs able
      to study the live virus, while NSDV, although highly pathogenic in naive animals,
      is not seen as a threat in developed countries, making it a low priority.
      Nevertheless, recent years have seen significant progress in our understanding of
      the biology of these viruses, particularly that of CCHFV, and this article seeks
      to draw together our existing knowledge to generate an overall picture of their
      molecular biology, underlining areas of particular ignorance for future studies. 

PMID- 24327095
TI  - Molecular detection and genetic characterization of kobuviruses and astroviruses
      in asymptomatic local pigs in East Africa.
AB  - In this study, swine fecal specimens (n = 251) collected from nursing and weaned
      piglets raised under smallholder production systems were screened for the
      presence of kobuviruses by RT-PCR. Porcine kobuviruses were detected in 13.1 %
      (33/251) of the samples. We demonstrated that porcine kobuvirus infections exist
      in indigenous pigs in Kenya and Uganda and that the prevalence was higher in
      young piglets than older pigs: nursing piglets (15 %), post-weaning (3-month-old)
      pigs (17 %), 4-month-old pigs (10 %). Genetic analysis of the partial RNA
      dependent RNA polymerase (RdRp) region (690 nt) revealed that kobuviruses
      circulating in East Africa are diverse, sharing nucleotide sequence identities
      ranging from 89.7 to 99.1 % and 88 to 92.3 % among them and with known porcine
      kobuviruses, respectively. The nucleotide sequence identities between our
      kobuvirus strains and those of human, bovine and canine kobuviruses were 69.4
      70.7 %, 73.1-74.4 % and 67-70.7 %, respectively. Additionally, upon sequencing
      selected samples that showed consistent 720-bp RT-PCR bands while using the same
      primer set, we detected porcine astroviruses in our samples belonging to type 2
      and type 3 mamastroviruses. To our knowledge, this study reports the first
      detection and molecular analysis of both porcine kobuviruses and astroviruses in
      an African region. Further studies are required to determine the role of these
      viruses in gastrointestinal infections of pigs in this region and to determine
      the genetic diversity of the circulating strains to develop accurate diagnostic
      tools and implement appropriate control strategies.

PMID- 24327096
TI  - Isolation and molecular characterization of Brazilian turkey reovirus from
      immunosuppressed young poults.
AB  - In this study, we investigated turkey reovirus (TReoV) in tissue samples from
      young birds, aged 15 days. RT-PCR for TReoV detected 3.3 % positive samples and
      TReoV was successfully isolated in Vero cells. Histological analysis of positive
      bursa of Fabricius (BF) revealed atrophied follicles and lymphocyte depletion.
      The number of CD8+, CD4+ and IgM+ cells was lower in infected BF. Phylogenetic
      analysis based on S3 gene showed that the Brazilian TReoV isolates clustered in a
      single group with 98-100 % similarity to TReoV strains circulating in the United
      States. This is the first indication that TReoV infection may be a contributing
      factor to immunosuppression in young birds.

PMID- 24327097
TI  - First complete genomic characterization of a porcine parvovirus 5 isolate from
      China.
AB  - To investigate porcine parvovirus 5 (PPV5) infections in swine herds in China,
      clinical specimens of piglet lungs were examined for the presence of PPV5 using a
      polymerase chain reaction method. A strain of PPV5 was detected, and its genome
      was sequenced and analyzed. In the sequence alignment and phylogenetic analysis,
      the Chinese PPV5 strain clustered into a distinct clade with the reference PPV5
      strains. These results provide direct evidence that PPV5 is present in pigs in
      China. Extensive epidemiological studies are warranted to determine the
      geographic distribution of PPV5 in China.

PMID- 24327098
TI  - Pulmonary inflammation and cell death in mice after acute exposure to air
      particulate matter from an industrial region of Buenos Aires.
AB  - Epidemiological studies have shown that air particulate matter (PM) can increase
      respiratory morbidity and mortality being the lungs the main target organ to PM
      body entrance. Even more, several in vivo and in vitro studies have shown that
      air PM has a wide toxicity spectra depending among other parameters, on its size,
      morphology, and chemical composition. The Reconquista River is the second most
      polluted river from Buenos Aires, and people living around its basin are
      constantly exposed to its contaminated water, soil and air. However, the air PM
      from the Reconquista River (RR-PMa) has not been characterized, and its
      biological impact on lung has yet not been assessed. Therefore, the present
      investigation was undertaken to study (1) RR-PMa morphochemical characteristic
      and (2) RR-PMa lung acute effects after intranasal instillation exposure through
      the analysis of three end points: oxidative stress, inflammation, and apoptosis.
      A single acute exposure of RR-PMa (1 mg/kg body weight) after 24 h caused
      significant (p < 0.05) enrichment in bronchoalveolar total cell number and
      polymorphonuclear (PNM) fraction, superoxide anion generation, production of pro
      inflammatory cytokines TNF-alpha and IL-6, and induction of apoptosis. It was
      also observed that in lung homogenates, none of the antioxidant enzymes assayed
      showed differences between exposed RR-PMa and control mice. These data
      demonstrate that air PM from the Reconquista River induce lung oxidative stress,
      inflammation, and cell death therefore represents a potential hazard to human
      health. 

PMID- 24327099
TI  - Millifluidics for chemical synthesis and time-resolved mechanistic studies.
AB  - Procedures utilizing millifluidic devices for chemical synthesis and time
      resolved mechanistic studies are described by taking three examples. In the
      first, synthesis of ultra-small copper nanoclusters is described. The second
      example provides their utility for investigating time resolved kinetics of
      chemical reactions by analyzing gold nanoparticle formation using in situ X-ray
      absorption spectroscopy. The final example demonstrates continuous flow catalysis
      of reactions inside millifluidic channel coated with nanostructured catalyst. 

PMID- 24327100
TI  - Beta-blockers and ivabradine in chronic heart failure: from clinical trials to
      clinical practice.
AB  - Beta-blockers have become one of the cornerstones of treatment of patients with
      heart failure (HF) and depressed left ventricular function, but in clinical
      practice only 30-35% of patients achieve the therapeutic target dose as
      established in randomized clinical trials. Moreover, high resting heart rate (HR)
      has emerged as a simple but relevant risk factor for cardiovascular events,
      including coronary artery disease and HF; also, it was found to have an
      independent prognostic value in patients with HF. Evidence that HR could be
      considered a good parameter to evaluate the quality of treatment in patients with
      HF has been suggested; of note, many patients maintain a resting HR >=70 beats
      per minute despite optimal beta-blocker therapy. In recent years, a new drug able
      to reduce HR, ivabradine, has been introduced in clinical practice, and its use
      in the clinical setting of HF patients has been recommended by current European
      Society of Cardiology (ESC) guidelines. Here we review the evidence of the
      prognostic role of HR in systolic HF and the potential relationship between HR
      lowering and the beneficial effects of beta-blockers; we will also analyze the
      reasons why an appropriate use of these drugs is seldom achieved in clinical
      practice, and review the evidence for the use of ivabradine in systolic HF in the
      clinical setting.

PMID- 24327101
TI  - Decoding the iceman's death?

PMID- 24327102
TI  - Primary combined neuroendocrine and squamous cell carcinoma of the maxillary
      sinus: report of a case with immunohistochemical and molecular characterization.
AB  - Neuroendocrine neoplasms represent a rare subset of tumors in the sinonasal
      tract. Combined tumors, with an endocrine and a non-neuroendocrine component, are
      exceedingly rare, and mainly consist of a combination of neuroendocrine carcinoma
      with adenocarcinomas. We present the clinico-pathologic and immunohistochemical
      features of a neuroendocrine carcinoma combined with squamous cell carcinoma,
      arising in the maxillary sinus. In addition, we evaluated the clonal origin of
      the two components through analysis of TP53 gene status. Both components were
      positive for cytokeratins AE1/AE3, while the squamous cell carcinoma was positive
      for cytokeratin 5/6 and p63, and the neuroendocrine carcinoma showed
      immunoreactivity for neuron specific enolase, chromogranin, synaptophysin and
      CD56. In situ hybridization for human papilloma virus and Epstein-Barr virus were
      negative in both components. A missense mutation in TP53 exon 7 (c.734G>C) and
      strong nuclear immunostaining for p53 were detected only in the neuroendocrine
      carcinoma. This suggests that the tumor either derived from one precursor cell
      with squamous differentiation, which underwent TP53 mutation and acquisition of a
      neuroendocrine phenotype, or it derived from two separate clones, one with
      mutated TP53 and neuroendocrine differentiation, and the other with wild type
      TP53 and squamous differentiation (collision tumor). 

PMID- 24327103
TI  - Current trends in stem cell therapy for improvement of bone quality.
AB  - As the average lifespan of humans continues to increase, improvement in the
      quality of life for elderly people is important. Among the most severe problems
      during aging are bone loss-associated diseases such as poor fracture healing and
      osteoporosis. Therapy-induced bone loss such as bisphosphonate-associated
      osteonecrosis of the jaw also increases in incidence with age. Most of the
      current treatment strategies are focused on antiresorptive and bone formation
      pharmacological agents, but it is hard to obtain appropriate bone augmentation
      and there are concerns regarding their long-term safety without side effects.
      Therefore, a novel method for improvement of bone quality is required, and stem
      cells are of great interest as potential therapeutic tools for diseases that
      remain without clinically effective therapies. In this review, we describe the
      concept of stem cell-based therapy and evaluate the current progress of cell
      therapy for the improvement of bone quality. In addition, we report and discuss a
      new clinical strategy in which improved bone quality was obtained by applying
      bone-marrow derived MSCs with platelet rich plasma in clinical therapy.

PMID- 24327104
TI  - Dental abnormalities and preventive oral care in Schimke immuno-osseous
      dysplasia.
AB  - BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare, severe, autosomal
      recessive disorder that results in spondyloepiphyseal dysplasia, renal
      dysfunction, immunodeficiency, facial dysmorphism and growth failure. Little is
      known about oral features associated with SIOD. Some of the dental anomalies
      encountered are specific to SIOD and have only been reported in individuals with
      SIOD. CASE REPORT: This paper describes the clinical and radiographic dental
      manifestations of SIOD in two Caucasian brothers. Both lived to be about 10 years
      old. After a variety of symptoms were reported, a diagnosis of SIOD was finally
      made when the brothers were, respectively, 5 and 8 years old. At that time,
      dental anomalies, such as dyschromia, bulbous crowns, short and thin roots, had
      not been taken into account to establish the diagnosis. However, knowledge of the
      dental features characteristic of this disease could have helped make the
      diagnosis. Although both were caries- and periodontal disease-free, special
      attention was focused on prevention, including dietary counselling, plaque
      control, oral hygiene instructions and the use of fluoridated toothpaste. FOLLOW
      UP: The two patients were followed every 6 months, for over 2 years (until their
      death), by both a private dentist and a university hospital dentist, which helped
      them maintain good oral health. Oral hygiene was assessed at each appointment and
      fissure sealants were placed by the private practitioner on their first permanent
      molars. CONCLUSION: This report describes dental anomalies specific to SIOD that
      could facilitate diagnosis. Clinicians and dentists should work in collaboration
      to diagnose and treat children with SIOD. These patients require regular and
      specific dental management because of their fragile health and their
      characteristic dental anomalies. Ideally, preventive visits should be scheduled
      every 6 months in addition to curative visits as needed.

PMID- 24327105
TI  - Goldstone and Higgs modes of photons inside a cavity.
AB  - Goldstone and Higgs modes have been detected in various condensed matter, cold
      atom and particle physics experiments. Here, we demonstrate that the two modes
      can also be observed in optical systems with only a few (artificial) atoms inside
      a cavity. We establish this connection by studying the U(1)/Z2 Dicke model where
      N qubits (atoms) coupled to a single photon mode. We determine the Goldstone and
      Higgs modes inside the super-radiant phase and their corresponding spectral
      weights by performing both 1/J = 2/N expansion and exact diagonalization (ED)
      study at a finite N. We find nearly perfect agreements between the results
      achieved by the two approaches when N gets down even to N = 2. The quantum finite
      size effects at a few qubits make the two modes quite robust against an
      effectively small counterrotating wave term. We present a few schemes to reduce
      the critical coupling strength, so the two modes can be observed in several
      current available experimental systems by just conventional optical measurements.

PMID- 24327106
TI  - Karrikins from plant smoke modulate bacterial quorum sensing.
AB  - The discovery that plant smoke contains germination stimuli has led to the
      identification of a new class of signaling molecules named karrikins. Here we
      report a potential second role for these molecules: in various bacterial species 
      A. tumefaciens, P. aeruginosa and V. harveyi- they modulate bacterial quorum
      sensing (QS), with very different outcomes. 

PMID- 24327108
TI  - Expression of adenosine A2b receptor in rat type II and III taste cells.
AB  - We previously demonstrated that equilibrative nucleoside transporter 1 was
      expressed in taste cells, suggesting the existence of an adenosine signaling
      system, but whether or not the expression of an adenosine receptor occurs in rat
      taste buds remains unknown. Therefore, we examined the expression profiles of
      adenosine receptors and evaluated their functionality in rat circumvallate
      papillae. Among adenosine receptors, the mRNA for an adenosine A2b receptor
      (A2bR) was expressed by the rat circumvallate papillae, and its expression level
      was significantly greater in the circumvallate papillae than in the non-taste
      lingual epithelium. A2bR-immunoreactivity was detected primarily in type II taste
      cells, and partial, but significant expression was also observed in type III
      ones, but there was no immunoreactivity in type I ones. The cAMP generation in
      isolated epithelium containing taste buds treated with 500 MUM adenosine or 10
      MUM BAY60-6583 was significantly increased compared to in the controls. These
      findings suggest that adenosine plays a role in signaling transmission via A2bR
      between taste cells in rats.

PMID- 24327109
TI  - In vitro characterization of a novel tissue engineered based hybridized nano and
      micro structured collagen implant and its in vivo role on tenoinduction,
      tenoconduction, tenogenesis and tenointegration.
AB  - Surgical reconstruction of large tendon defects is technically demanding. Tissue
      engineering is a new option. We produced a novel tissue engineered, collagen
      based, bioimplant and in vitro characterizations of the implant were
      investigated. In addition, we investigated role of the collagen implant on the
      healing of a large tendon defect model in rabbits. A two cm length of the left
      rabbit's Achilles tendon was transected and discarded. The injured tendons of all
      the rabbits were repaired by Kessler pattern to create and maintain a 2 cm tendon
      gap. The collagen implant was inserted in the tendon defect of the treatment
      group (n = 30). The defect area was left intact in the control group (n = 30).
      The animals were euthanized at 60 days post injury (DPI) and the macro- micro-
      and nano- morphologies and the biomechanical characteristics of the tendon
      samples were studied. Differences of P < 0.05 were considered significant. The
      host graft interaction was followed at various stages of tendon healing, using
      pilot animals. At 60 DPI, a significant increase in number, diameter and density
      of the collagen fibrils, number and maturity of tenoblasts and tenocytes,
      alignment of the collagen fibrils and maturity of the elastic fibers were seen in
      the treated tendons when compared to the control ones (P < 0.05). Compared to the
      control lesions, number of inflammatory cells, amount of peritendinous adhesions
      and muscle fibrosis and atrophy, were significantly lower in the treated lesions
      (P < 0.05). Treatment also significantly increased load to failure, tensile
      strength and elastic modulus of the samples as compared with the control ones.
      The collagen implant properly incorporated with the healing tissue and was
      replaced by the new tendinous structure which was superior both ultra
      structurally and physically than the loose areolar connective tissue regenerated
      in the control lesions. The results of this study may be valuable in the clinical
      practice. 

PMID- 24327110
TI  - Olive oil based novel thermo-reversible emulsion hydrogels for controlled
      delivery applications.
AB  - Gels have been considered as a popular mode of delivering medicament for the
      treatment of sexually transmitted diseases (STDs) (e.g. human immunodeficiency
      virus, bacterial vaginosis, epididymitis, human papillomavirus infection and
      condylomata acuminata etc.). The present study discusses the development of novel
      olive oil based emulsion hydrogels (EHs) using sorbitan monopalmitate as the
      structuring agent. The developed EHs may be tried as drug delivery vehicle for
      the treatment of STDs. The formation of EHs was confirmed by fluorescence and
      confocal microscopy. FTIR studies suggested intermolecular hydrogen bonding
      amongst the components of the EHs. X-ray diffraction study suggested the
      amorphous nature of the EHs. The developed EHs have shown non-Newtonian flow
      behavior. The EHs were found to be biocompatible. The formulations were able to
      effectively deliver two model antimicrobial drugs (e.g. ciprofloxacin and
      metronidazole), commonly used in the treatment of the STDs. 

PMID- 24327111
TI  - Nanoparticles of deoxycholic acid, polyethylene glycol and folic acid-modified
      chitosan for targeted delivery of doxorubicin.
AB  - Chitosan (CS) was first modified hydrophobically with deoxycholic acid (DCA) and
      then with polyethylene glycol (PEG) to obtain a novel amphiphilic polymer (CS-DCA
      PEG). This was covalently bound to folic acid (FA) to develop nanoparticles (CS
      DCA-PEG-FA) with tumor cell targeting property. The structure of the conjugates
      was characterised using Fourier transform infrared and (1)H nuclear magnetic
      resonance spectroscopy and X-ray diffraction. Based on self-aggregation, the
      conjugates formed nanoparticles with a low critical aggregation concentration of
      0.035 mg/ml. The anti-cancer drug doxorubicin (DOX) was encapsulated into the
      nanoparticles with a drug-loading capacity of 30.2 wt%. The mean diameter of the
      DOX-loaded nanoparticles was about 200 nm, with a narrow size distribution.
      Transmission electron microscopy images showed that the DOX-loaded nanoparticles
      were spherical. The drug release was studied under different conditions.
      Furthermore, the cytotoxic activities of DOX in CS-DCA-PEG-FA nanoparticles
      against folate receptor (FR)-positive HeLa cells and FR-negative fibroblast 3T3
      cells were evaluated. These results suggested that the CS-DCA-PEG-FA
      nanoparticles may be a promising vehicle for the targeting anticancer drug to
      tumor cells. 

PMID- 24327112
TI  - Cytocompatibility evaluation of different biodegradable magnesium alloys with
      human mesenchymal stem cells.
AB  - In the last few years, the use of biodegradable magnesium (Mg) alloys has evoked
      great interest in the orthopedic field due to great advantages over long-term
      implant materials associated with various side effects like allergy and
      sensitization and consequent implant removal surgeries. However, degradation of
      these Mg alloys results in ion release, which may cause severe cytotoxicity and
      undesirable complications after implantation. In this study, we investigated the
      cytological effects of various Mg alloys on cells that play an important role in
      bone repair. Eight different magnesium alloys containing varying amounts of Al,
      Zn, Nd and Y were either incubated directly or indirectly with the osteosarcoma
      cell line Saos-2 or with uninduced and osteogenically-induced human mesenchymal
      stem cells (MSCs) isolated from bone marrow specimens obtained from the femoral
      shaft of patients undergoing total hip replacement. Cell viability, cell
      attachment and the release of ions were investigated at different time points in
      vitro. During direct or indirect incubation different cytotoxic effects of the Mg
      alloys on Saos-2 cells and osteogenically-induced or uninduced MSCs were
      observed. Furthermore, the concentration of degradation products released from
      the Mg alloys differed. Overall, Mg alloys MgNd2, MgY4, MgAl9Zn1 and MgY4Nd2
      exhibit good cytocompatibility. In conclusion, this study reveals the necessity
      of cytocompatibility evaluation of new biodegradable magnesium alloys with cells
      that will get in direct contact to the implant material. Furthermore, the use of
      standardized experimental in vitro assays is necessary in order to reliably and
      effectively characterize new Mg alloys before performing in vivo experiments. 

PMID- 24327114
TI  - Decolorization of palm oil mill effluent using growing cultures of Curvularia
      clavata.
AB  - Agricultural wastewater that produces color are of environmental and health
      concern as colored effluent can produce toxic and carcinogenic by-products. From
      this study, batch culture optimization using response surface methods indicated
      that the fungus isolated from the pineapple solid waste, Curvularia clavata was
      able to decolorize sterile palm oil mill effluent (POME) which is mainly
      associated with polyphenol and lignin. Results showed successful decolorization
      of POME up to 80 % (initial ADMI [American Dye Manufacturing Index] of 3,793)
      with 54 % contributed by biosorption and 46 % by biodegradation after 5 days of
      treatment. Analysis using HPLC and GC-MS showed the degradation of color causing
      compound such as 3-methoxyphenyl isothiocynate and the production of new
      metabolites. Ecotoxicity test indicated that the decolorized effluent is safe for
      discharge. To determine the longevity of the fungus for a prolonged
      decolorization period, sequential batch decolorization studies were carried out.
      The results showed that lignin peroxidase and laccase were the main ligninolytic
      enzymes involved in the degradation of color. Carboxymethyl cellulase (CMCase)
      and xylanase activities were also detected suggesting possible roles of the
      enzymes in promoting growth of the fungus which consequently contributed to
      improved decolorization of POME. In conclusion, the ability of C. clavata in
      treating color of POME indicated that C. clavata is of potential use for
      decolorization and degradation of agricultural wastewater containing polyphenolic
      compounds.

PMID- 24327113
TI  - Environmental effects of anticholinesterasic therapeutic drugs on a crustacean
      species, Daphnia magna.
AB  - The presence of pharmaceutical drugs in the environment is an important field of
      toxicology, since such residues can cause deleterious effects on exposed biota.
      This study assessed the ecotoxicological acute and chronic effects of two
      anticholinesterasic drugs, neostigmine and pyridostigmine in Daphnia magna. Our
      study calculated 48 h-EC50 values for the immobilization assay of 167.7 MUg L(-1)
      for neostigmine and 91.3 MUg L(-1) for pyridostigmine. In terms of feeding
      behavior, we calculated a 5 h-EC50 for filtration rates of 7.1 and 0.2 MUg L(-1)
      for neostigmine and pyridostigmine, respectively; for the ingestion rates, the
      calculated EC50 values were, respectively, 7.5 and 0.2 MUg L(-1) for neostigmine
      and pyridostigmine. In the reproduction assay, the most affected parameter was
      the somatic growth rate (LOECs of 21.0 and 2.9 MUg L(-1) for neostigmine and
      pyridostigmine, respectively), followed by the fecundity (LOECs of 41.9 and 11.4
      MUg L(-1) for neostigmine and pyridostigmine, respectively). We also determined a
      48 h-IC50 for cholinesterase activity of 1.7 and 4.5 MUg L(-1) for neostigmine
      and pyridostigmine, respectively. These results demonstrated that both compounds
      are potentially toxic for D. magna at concentrations in the order of the MUg L(
      1).

PMID- 24327115
TI  - Human health risk from organ-specific accumulation of toxic metals and response
      of antioxidants in edible fish species from Chenab River, Pakistan.
AB  - In the current study, the bioaccumulation of essential and nonessential metals
      and related antioxidant activity were analyzed in three organs (muscle, gills,
      and liver) of herbivorous (HF) and carnivorous (CF) edible fish of Chenab River.
      The comparative analysis revealed a more heterogeneous accumulation of metals in
      the muscles of HF fish than that of CF fish [chromium (Cr, 3.4 MUg g(-1)), cobalt
      (Co, 1.7 MUg g(-1)), copper (Cu, 3 MUg g(-1)), and iron (Fe, 45 MUg g(-1)) versus
      Cr (1.3 MUg g(-1)), Co (0.1 MUg g(-1)), Cu (1.1 MUg g(-1)), and Fe (33 MUg g(
      1)), respectively, P<0.001]. These results implied an organ-specific accumulation
      of metals at different trophic levels. According to logistic regression analysis,
      the bioaccumulation of metals had marked differences in HF and CF. The
      antioxidant activity was significantly related to the tissue type and the metals
      to which the organs are exposed to. The liver of CF fish had a higher activity of
      antioxidant superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and
      lipid peroxidase (LPO) than that of HF (P<0.05). LPO and guaiacol peroxidase
      (POD) in both groups were associated with a number of metals, but in HF, cadmium
      (Cd), Cr, Pb, and Zn were more related with the LPO and SOD activities. Moreover,
      Cd, Co, Fe, Pb, Ni, Cu, and Zn were above the permissible limits set by various
      agencies. In numerous cases, our results were even higher than those previously
      reported in the literature. The results provide an insight into the pollution
      pattern of Chenab River. These results may be helpful in the future to identify
      biomarkers of exposure in aquatic organisms.

PMID- 24327116
TI  - The local and regional atmospheric oxidants at Athens (Greece).
AB  - In the present study, the investigation of the levels of the local and regional
      oxidants concentration at Athens, Greece, is attempted by analyzing the
      observations obtained at an urban and a rural station, during 2001-2011 and 2007
      2011, respectively. A progressive increase of the daytime and nighttime average
      of [NO2]/[Ox] versus [NOx] is observed showing a larger proportion of Ox in the
      form of NO2 when the level of NOx increases. Similar results are observed when
      studying the variation of mean values of [NO2]/[NOx] versus [NOx]. The results
      obtained when compared with those that have earlier detected elsewhere, revealed
      similarities and discrepancies that are discussed in detail. The parameterized
      curves that are presented for the first time in this paper may be used by the air
      quality planners to track the trends in other cities also, and to understand what
      is or was driving them. 

PMID- 24327117
TI  - Zinc pharmacokinetic parameters in the determination of body zinc status in
      children.
AB  - BACKGROUND/OBJECTIVES: Serum or tissue zinc concentrations are often used to
      assess body zinc status. However, all of these methods are relatively inaccurate.
      Thus, we investigated three different kinetic methods for the determination of
      zinc clearance to establish which of these could detect small changes in the body
      zinc status of children. SUBJECTS/METHODS: Forty apparently healthy children were
      studied. Renal handling of zinc was investigated during intravenous zinc
      administration (0.06537 mg Zn/kg of body weight), both before and after oral zinc
      supplementation (5 mg Zn/day for 3 months). Three kinetic methods were used to
      determine zinc clearance: CZn-Formula A and CZn-Formula B were both used to
      calculate systemic clearance; the first is a general formula and the second is
      used for the specific analysis of a single-compartment model; CZn-Formula C is
      widely used in medical practices to analyze kinetic routine. RESULTS: Basal serum
      zinc values, which were within the reference range for healthy children,
      increased significantly after oral zinc supplementation. The three formulas used
      gave different results for zinc clearance both before and after oral zinc
      supplementation. CZn-Formula B showed a positive correlation with basal serum
      zinc concentration after oral supplementation (R2=0.1172, P=0.0306). In addition,
      CZn-Formula B (P=0.0002) was more effective than CZn-Formula A (P=0.6028) and CZn
      Formula C (P=0.0732) in detecting small variations in body zinc status.
      CONCLUSIONS: All three of the formulas used are suitable for studying zinc
      kinetics; however, CZn-Formula B is particularly effective at detecting small
      changes in body zinc status in healthy children.

PMID- 24327118
TI  - The effects of second-generation antipsychotics on food intake, resting energy
      expenditure and physical activity.
AB  - Second-generation antipsychotics (SGA) are associated with weight gain and
      metabolic alterations including hyperglycemia, dyslipidemia, hypertension and
      metabolic syndrome. These metabolic side effects increase cardiovascular risk and
      are related to medication non-compliance. Patients without previous exposure to
      these or other antipsychotic drugs (naive patients) seem to be more prone to
      develop these metabolic abnormalities. The mechanisms behind weight gain can be
      an increase in food intake and/or a decrease in energy expenditure. This review
      comprehensively examines the current knowledge on the impact of these drugs on
      food intake and energy expenditure. The influence of these drugs on appetite and
      food intake (total caloric intake and food sources) is reviewed as well as the
      evidence of abnormal eating behaviors. The studies evaluating the effect on
      resting energy expenditure are critically examined, taking into account the
      influence of body composition and previous exposure to antipsychotics (naive vs
      non-naive patients). Finally, the influence of these drugs on physical activity
      is also discussed. The knowledge of the mechanisms of weight gain in patients
      starting these drugs may be useful to further prompt research in this field and
      ameliorate the metabolic side effects associated with these treatments.

PMID- 24327119
TI  - Back-transformation of treatment differences--an approximate method.
AB  - BACKGROUND/OBJECTIVES: Transformation of outcomes is frequently used in the
      analysis of studies in clinical nutrition. However, back-transformation of
      estimated treatment means and differences is complicated by the nonlinear nature
      of the transformations. It is not straightforward to obtain an estimated
      treatment difference that can be interpreted without any reference to the
      additional predictors included in the statistical model; and moreover, standard
      errors are not easily available. The aim of this work was to provide a generally
      applicable, yet operational procedure for obtaining back-transformed estimated
      differences, and corresponding standard errors and 95% confidence intervals.
      SUBJECTS/METHODS: Based on data from two randomized controlled studies and an
      exemplary data set that had all previously been published, we evaluated our
      approximate procedure by comparing results for different approaches for showing
      back-transformed estimated treatment differences. RESULTS: Estimated differences
      obtained on logarithm, square root and reciprocal square root-transformed scales
      were back-transformed into estimated differences on the original scales, and
      these estimates were in good agreement with the results reported by the original
      studies. CONCLUSIONS: The proposed approximate procedure provides a flexible
      approach for obtaining quite accurate back-transformed estimated differences in
      terms of medians and for deriving the corresponding standard errors.

PMID- 24327122
TI  - Total body potassium revisited.

PMID- 24327120
TI  - Effect of inflammation on handgrip strength in the non-critically ill is
      independent from age, gender and body composition.
AB  - BACKGROUND/OBJECTIVES: We investigated whether C-reactive protein (CRP) as
      indicator of acute inflammation is associated with maximal isometric handgrip
      strength in non-critically ill patients. SUBJECTS/METHODS: Handgrip strength was
      measured with Jamar dynamometer in 620 hospitalized patients (56.4+/-15.9 years
      old, 52.3% men). CRP was measured with immunoturbidimetric assay. Fat free mass
      (FFM) was assessed by bioelectrical impedance analysis. A general linear model
      regression analysis corrected for confounding variables such as age, sex, FFM,
      body mass index, comorbidity count and diagnosis category (malignant/benign
      disease) was performed to test the association between elevated levels of CRP and
      handgrip strength. RESULTS: CRP was an independent predictor of grip strength
      (CRP: beta-coefficient: -0.169, P=0.018) even after adjustment for relevant
      confounders. All groups with inflammation showed significant reduction in
      handgrip strength, corresponding to a loss of ~1.6 kg in mild inflammation, 3.2
      kg in moderate inflammation and 2.9 kg in severe inflammation compared with
      patients without inflammation. DISCUSSION: Our data demonstrate the independent
      association between inflammation and handgrip strength in non-critically ill
      patients. If not corrected, reduced strength may have implications for the
      patients' functional status and prognosis. Increasing physical activity and
      resistance training during convalescence are recommended.

PMID- 24327121
TI  - Oxidative stress markers and micronutrients in maternal and cord blood in
      relation to neonatal outcome.
AB  - BACKGROUND/OBJECTIVES: Oxidative stress and micronutrient deficiencies have been
      related to lower birth weight (BW), small for gestational age (SGA) offspring and
      preterm delivery. SUBJECTS/METHODS: The relation between neonatal outcome (BW,
      head circumference, SGA, preterm delivery) with markers of oxidative stress and
      micronutrients in maternal and cord blood was to be examined. Oxidative stress
      markers (protein carbonyls (PrCarb), 3-nitrotyrosine (3NT), malondialdehyde
      (MDA)), total protein concentration and lipid-soluble micronutrients
      (carotenoids, retinol, tocopherols) were measured in 200 newborns (11% preterms,
      13% SGA) and 151 mothers. Associations between target parameters in cord plasma
      and maternal serum with BW, head circumference and risk of being SGA or preterm
      were explored. RESULTS: Maternal protein concentration, PrCarb, MDA and all lipid
      soluble micronutrients were significantly higher compared with newborns, except
      for 3NT, which was significantly elevated in newborns. Newborn parameters
      correlated positively with those of mothers. Preterms had lower proteins and
      retinol but higher PrCarb than terms. Maternal PrCarb and retinol were inversely
      associated with BW and head circumference. Mothers with PrCarb, MDA and retinol
      in the highest quintile had a 3.3-fold (0.9; 12.1), 2.1-fold (0.7; 6.4) and 3.3
      fold (1.2; 9.4) risk, respectively, for delivering an SGA newborn, whereas the
      lowest quintile of retinol in cord blood was associated with an increased risk
      for preterm delivery. CONCLUSIONS: Oxidative stress (elevated PrCarb) was
      associated with lower BW/head circumference and SGA. Inadequate hemodilution may
      explain the inverse relation of maternal retinol with BW and head circumference,
      and the association between highest maternal retinol and risk for SGA.

PMID- 24327123
TI  - Quality of dietary intake in relation to body composition in patients with
      chronic obstructive pulmonary disease eligible for pulmonary rehabilitation.
AB  - BACKGROUND/OBJECTIVES: A poor dietary quality may accelerate disturbances in body
      composition in chronic obstructive pulmonary disease (COPD), but only limited
      studies have investigated dietary intake from this perspective. The objective of
      the current study was to investigate dietary intake in relation to low fat-free
      mass and abdominal obesity in COPD. SUBJECTS/METHODS: Dietary intake was assessed
      by means of a cross-check dietary history method in 564 COPD patients referred
      for pulmonary rehabilitation. The Dutch Food Composition Database was used to
      calculate nutrient intake, which was compared with the 2006 recommendations from
      the Dutch Health Council. Body composition was assessed by DEXA scan. RESULTS: In
      general, the reported intake of macronutrients represented a typical western
      diet. With regard to micronutrients, vitamin D and calcium intakes were below the
      recommended levels in the majority of patients (>75%), whereas vitamin A, C and E
      intakes were below the recommended levels in over one-third of patients. Patients
      with inadequate vitamin D intake more frequently reported a low intake of protein
      (P=0.02) and micronutrients (P<0.001). Patients with a low fat-free mass index
      (FFMI) more often had low intake of protein, while abdominally obese patients
      more often had low intake of protein and most micronutrients (P<0.05). Patients
      with both low FFMI and abdominal obesity appeared most often to be consuming a
      poor-quality diet. CONCLUSIONS: Our data indicate that dietary quality is low in
      COPD patients referred for pulmonary rehabilitation and differs between patients
      with different body composition profiles.

PMID- 24327125
TI  - Conclusiveness of the Cochrane reviews in nutrition: a systematic analysis.
AB  - BACKGROUND/OBJECTIVE: To assess the conclusiveness of the Cochrane Reviews (CRs)
      in the field of Nutrition, we tested the hypotheses that: (1) the majority of CRs
      is inconclusive; (2) the majority of CRs recognizes the need for further and
      better studies and (3) the ability to reach a conclusion is dependent on the
      number of studies performed and number of patients enrolled. SUBJECTS/METHODS: We
      selected all 87 CRs in the field of Nutrition available in Cochrane library. Each
      CR was analyzed for the number of randomized clinical trials (RCTs) found, number
      of RCTs included for analysis, number of patients enrolled, the stated need for
      further studies and the reason(s) for it and the conclusiveness of the CR.
      RESULTS: Fifty-six out of eighty-seven CRs (64.4%) were conclusive. The average
      number of available articles, the percentage of articles included, the average
      number of RCT's retained in the analyses and the total cumulative number of
      patients enrolled in the studies retained for analysis were significantly higher
      in conclusive CRs than in non-conclusive ones. The majority of inconclusive CRs
      (70.9%) recognized the need for further studies, a percentage not significantly
      different from that found in conclusive ones (58.9%, P=0.26). The percentage of
      conclusive CRs was not affected by year of publication. CONCLUSIONS: The majority
      of CRs in Nutrition is conclusive, but most of them emphasize the need for
      further studies. The ability for a CR to reach a conclusion is affected by the
      cumulative patient sample size and number of RCT's included in the analysis.

PMID- 24327124
TI  - Radiation enteritis leading to intestinal failure: 1994 patient-years of
      experience in a national referral centre.
AB  - BACKGROUND/OBJECTIVES: Chronic radiation enteritis (RE) has been reported in up
      to 20% of patients receiving pelvic radiotherapy and can lead to intestinal
      failure (IF), accounting for 3.9% of new registrants for home parenteral
      nutrition (HPN) in the UK annually. Our aim is to report nutritional and survival
      outcomes for patients with RE referred to a national IF unit. SUBJECTS/METHODS: A
      retrospective study of all new admissions over a 13-year period at the Intestinal
      Failure Centre, Manchester, UK. Data are presented as median (range). RESULTS:
      Twenty-three (3.8%) of 611 patients were admitted with IF secondary to RE. The
      primary site of malignancy was genitourinary in 17 (74%) patients. Radiotherapy
      was administered 9.5 (1-42) years previously. Patients underwent 2 (1-5)
      laparotomies prior to intestinal failure unit (IFU) admission. Twelve (52%)
      patients were admitted with intestinal obstruction and 11 (48%) with intractable
      weight loss and/or high output fistulae/stomas. Additional conditions
      contributing to IF were noted in 11 (48%) patients. Twenty-two (96%) patients had
      2 (1-5) laparotomies prior to IFU referral. At discharge, 5 (22%) patients
      resumed oral diet without the need for artificial nutrition support, 3 (13%)
      required enteral feeding and 13 (56%) commenced HPN. The 10-year survival of the
      patient cohort was 48.2%. CONCLUSIONS: Surgical intervention is infrequently
      required, whereas the majority of patients with IF secondary to RE require long
      term HPN. The judicious use of surgery in selected patients, coupled with an
      aggressive medical strategy to detect and treat contributing factors, and optimal
      enteral feeding may allow a modest proportion of patients with IF secondary to RE
      to achieve independence from PN.

PMID- 24327126
TI  - Refractory iron-deficiency anemia and autoimmune atrophic gastritis in pediatric
      age group: analysis of 8 clinical cases.
AB  - INTRODUCTION: Refractory iron-deficiency anemia with no obvious etiology in
      pediatric age can be a puzzling problem. Screening of iron malabsorption
      conditions, including autoimmune atrophic gastritis (AAG), is emerging as a
      priority in the investigational procedure. MATERIALS AND METHODS: Retrospective
      analysis of clinical process of children/adolescents with the diagnosis of AAG.
      RESULTS: Eight patients (aged between 4.7 and 18 years old) were identified. The
      diagnosis was triggered on the basis of high serum gastrin levels and strong
      positivity of antiparietal cell antibodies. Upper endoscopy and biopsy revealed
      atrophic gastritis in all patients, with 2 of them with intestinal metaplasia.
      Four patients presented with Helicobacter pylori infection object of eradication
      therapy. After a medium follow-up of 36.6 months, antiparietal cell antibodies
      and hypergastrinemia did not show evidence of regression. Of the 3 patients who
      underwent endoscopic reevaluation, a similar anatomo-pathologic pattern was
      observed in 2 and intestinal metaplasia in 1 patient. Normalization of
      hematological parameters was achieved, using alternative iron formulas.
      CONCLUSIONS: AAG must be recognized as a pathology affecting pediatric patients.
      Gastric autoimmune lesion is a chronic process with potential evolution to
      malignancy. Management guidelines in childhood are not available. Their
      elaboration is important considering an important risk factor in these age group:
      a long life expectancy.

PMID- 24327127
TI  - Cerebral vascular abnormalities in pediatric patients with sickle cell disease
      after hematopoietic cell transplant.
AB  - OVERVIEW: Stroke is a common sequela of sickle cell disease (SCD). Patients with
      SCD who undergo hematopoietic stem cell transplantation (HSCT) with successful
      engraftment will not experience sickling. This ameliorates one aspect of stroke
      risk; however, the significance of preexisting cerebrovascular abnormalities
      remains unclear. METHODS: We performed a literature search for neurological
      outcomes following HSCT for SCD. We searched for relevant neuroimaging and
      neurosurgical protocols. We identified 4 unique studies encompassing 196
      patients. Of these, 81 had a history of a stroke, transient ischemic attack
      (TIA), cognitive dysfunction or cerebrovascular abnormalities identified by
      pretransplant neuroimaging, achieved stable engraftment, and had long-term follow
      up. RESULTS: Of the 81 patients, 1 had peritransplant (10 days prior transplant
      to 50 days posttransplant) TIA. One had posttransplant TIA within 36 to 72
      months. None had strokes. Forty-five underwent cerebral imaging at nonuniform
      intervals. Among this group, 32 (71%) had stable cerebrovascular abnormalities on
      imaging, 6 (13%) had improvement, and 7 (16%) showed worsening. CONCLUSIONS:
      Cerebrovascular abnormalities identified on neuroimaging may stabilize, improve,
      or worsen in patients after successful HSCT. Some patients may have neurological
      events such as TIA. Neurological outcomes in children with SCD post-HSCT have
      been inadequately studied.

PMID- 24327128
TI  - Superselective intracerebral catheterization for administration of oncolytic
      virotherapy in a case of diffuse intrinsic pontine glioma.
AB  - New therapies are needed to improve current results in diffuse intrinsic pontine
      glioma. We present here the initial experience of administering Celyvir,
      autologous mesenchymal stem cells infected with ICOVIR-5, an oncolytic adenovirus
      that selectively replicates in cancer cells, by means of superselective intra
      arterial delivery, in a patient diagnosed of diffuse intrinsic pontine glioma.
      Feasibility, safety, and morbidity rates of the superselective catheterization
      technique are comparable with those of diagnostic angiography. The intra-arterial
      approach warrants a greater contact of the mesenchymal stem cells with the tumor
      mass, and minimizes hemorrhages or vascular disruption. The tolerance to the 2
      administrations was excellent, with no acute or delayed adverse effect,
      underscoring the feasibility of this technique for the delivery of virotherapies
      and/or cellular therapies in this location. 

PMID- 24327129
TI  - High-dose cyclophosphamide for the treatment of refractory T-cell acute
      lymphoblastic leukemia in children.
AB  - Despite an almost 80% overall survival rate in pediatric T-cell acute
      lymphoblastic leukemia (T-ALL), there is a subset of patients who are refractory
      to standard chemotherapy regimens and could benefit from novel treatment
      approaches. Over a 2-year period, we treated 5 pediatric patients with refractory
      T-ALL, aged 3 to 15 years, with high-dose cyclophosphamide (CY) at a dose of 2100
      mg/m for 2 consecutive days either alone (n=1) or in combination with other
      chemotherapy agents (n=4). Four of these 5 patients had a 1.5 log decrease in
      disease burden. Three of the 5 patients had no evidence of minimal residual
      disease (MRD) after high-dose CY. One patient developed transient grade 4
      transaminitis and 1 patient developed grade 3 typhlitis. All 5 patients
      ultimately proceeded to hematopoietic stem cell transplant when MRD levels were
      <0.01%. Pediatric T-ALL patients with persistent MRD after treatment with
      conventional chemotherapy may respond to CY at escalated dosing. 

PMID- 24327130
TI  - Respiratory syncytial virus infections in children with cancer.
AB  - Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract
      infections (LRTIs) in children, especially those with cancer. Data on RSV
      infections in this vulnerable population is limited. We conducted a retrospective
      study of all RSV infections in children with cancer from 1998 to 2009 to
      determine characteristics and outcomes of these infections, identify risk factors
      for LRTI and mortality, and the effect of antiviral therapy on these outcomes. We
      identified 59 patients with a median age of 5 years; 53% had hematologic
      malignancy, 32% were hematopoietic stem cell transplant recipients, 39% had
      received corticosteroids, and 76% cytotoxic chemotherapy within 1 month before
      RSV infection. LRTI developed in 22 (37%) patients with a trend of higher rate in
      males (odds ratio=2.57 [0.86-7.62], P=0.09) and children with lymphocytopenia
      (odds ratio=2.95 [0.86-10.12], P=0.085). No significant differences were observed
      in the rates of progression to LRTI (3/10 [30%] vs. 19/49 [39%], P=0.729) and RSV
      associated mortality (0/10 [0%] vs. 3/49 [6%], P=0.422) for patients receiving
      antiviral therapy at upper respiratory tract infection stage compared with those
      who did not. However, patients with LRTI had significantly better outcomes when
      treated with aerosolized ribavirin plus immunomodulators (mainly palivizumab)
      when compared with aerosolized ribavirin alone (mortality rates: 0/6 [0%] vs. 3/4
      [75%], P=0.03). Ribavirin did not show any benefit in reducing LRTI or mortality;
      however, addition of palivizumab to the treatment regimen may be potentially
      beneficial, especially for children with LRTI. 

PMID- 24327131
TI  - Coping and coping assistance among children with sickle cell disease and their
      parents.
AB  - The ways in which a family copes with the physical and psychosocial burdens of
      sickle cell disease (SCD) can influence the child and family functioning.
      However, few studies have examined SCD-related stressors beyond pain or how
      children and parents cope with these stressors. This study aimed to describe
      child coping and parent attempts to help their children cope (ie, coping
      assistance) with a range of SCD stressors by using a triangulated mixed methods
      design. We also explored convergence between findings from qualitative interviews
      and quantitative coping inventories. Fifteen children (aged 6 to 14 years) with
      SCD and their parents (N=15) completed semistructured interviews and self-report
      measures to assess SCD-related stressors, coping, and coping assistance
      strategies. Findings indicate that children experience numerous stressors related
      to SCD and its treatment, including, but not limited to, pain. To manage these
      stressors, families employ a range of approach and avoidance-oriented coping
      strategies. Quantitative and qualitative assessments provided complementary and
      unique contributions to understanding coping processes among children with SCD
      and their parents. Examining a broad range of stressors and integrating multiple
      assessment methods helps improve our understanding of coping with pediatric SCD,
      which may inform clinical practice and family-focused intervention development.

PMID- 24327132
TI  - Effect of margin width on local recurrence in triple-negative breast cancer
      patients treated with breast-conserving therapy.
AB  - BACKGROUND: The effect of increasing negative margin width after breast
      conserving therapy (BCT) on local recurrence (LR) is controversial. LR rates vary
      by subtype, with the highest rates seen in triple-negative breast cancer (TNBC).
      This study examined LR rates in relationship to margin width in TNBC treated with
      BCT. METHODS: Women with TNBC who underwent BCT between 1999 and 2009 were
      identified. Margins were defined as positive (ink on tumor), 0.1-2.0, and 2 mm.
      Patients with positive margins were excluded. Statistical comparisons were by t
      test, Fisher's exact test, and Wilcoxon rank sum test. Cumulative incidence of LR
      was compared by competing-risks methodology. RESULTS: Of 535 cancers, 71 had
      margins <=2 mm and 464 had margins >2 mm. At a median follow-up of 84 months
      (range 8-165 months), there were 37 local, 18 regional, and 77 distant
      recurrences or deaths as first events. Ten patients had a locoregional recurrence
      before planned radiotherapy and were excluded from cumulative incidence analyses.
      The cumulative incidence of LR at 60 months for margins <=2 mm was 4.7 % (95 %
      confidence interval 0-10.0) and for >2 mm was 3.7 % (1.8, 5.5) (p = 0.11). After
      controlling for chemotherapy and tumor size, there was no difference in LR
      between the two margin groups (p = 0.06). A difference in the risk of distant
      recurrence or death was not observed (p = 0.53). CONCLUSIONS: Margin width of >2
      mm was not associated with reduced LR rates. These data support a negative margin
      definition of no ink on tumor, even in this high-risk TNBC cohort.

PMID- 24327133
TI  - [Panton-Valentine leukocidin in patients with chronic wounds. Results from a
      clinical investigation in 100 patients].
AB  - BACKGROUND: The toxin Panton-Valentine leukocidin (PVL) produced by S. aureus is
      known as a virulence factor that leads to severe infections of skin and soft
      tissue. However the effect of PVL on wound healing is not known yet. Therefore we
      examined the detection rate of PVL in patients with chronic wounds. PATIENTS AND
      METHODS: The study included 100 patients with chronic wounds of the lower limb.
      We determined in all S. aureus isolates the presence of the PVL gene using a PCR
      technique. RESULTS: Altogether 94% of the patients had a leg ulcer, while 6% had
      a foot ulcer; 65% were women. PVL was found in two patients. One of the strains
      was methicillin-resistant (MRSA) and the other was methicillin-sensitive (MSSA).
      CONCLUSION: In our investigation there was detection rate for PVL of 2% of all S.
      aureus isolates in patients with chronic wounds of the lower extremities.
      Although the role of PVL as a virulence factor of S. aureus in wound healing
      remains unclear, the detection of PVL should be taken as a cause for a consequent
      topical antimicrobial wound therapy because of the increased risk of serious
      infections.

PMID- 24327134
TI  - C3a, C5a renal expression and their receptors are correlated to severity of IgA
      nephropathy.
AB  - BACKGROUND: IgA nephropathy (IgAN) is the most common primary kidney disease,
      often leading to chronic renal failure. Complement activation products C3a and
      C5a have broad pro-inflammatory potential through their receptors, C3aR and C5aR,
      and contribute to the pathogenesis of several inflammatory and autoimmune
      diseases, but their roles in IgAN are poorly defined. PURPOSE: This study aimed
      to establish correlations between renal C3a, C5a, C3aR, C5aR, or serum/urinary
      C3a, C5a with clinical features and renal histopathology in patients with IgAN.
      METHODS: Eighty-three patients with renal biopsy proven IgAN were investigated.
      Thirty patients fulfilled Haas's II, 30 fulfilled Haas's III and 23 fulfilled
      Haas's IV criteria. Deposition of C3a and C5a was assessed by
      immunohistochemistry. C3aR and C5aR mRNAs and proteins in kidney tissue were
      examined by real-time quantitative PCR (RT-qPCR) and immunohistochemical
      staining, respectively. C3a and C5a levels were quantified by ELISA in serum and
      urine samples of 30 IgAN patients, 10 control subjects and 10 septic patients.
      RESULTS: Renal C3a and C5a deposition and C3aR and C5aR expression increased with
      increasing grades of renal pathology in IgAN patients. They positively correlated
      with proteinuria and serum creatinine (SCr), but not serum C-reactive protein
      (CRP) or complement 3 (C3). Serum C3a and C5a increased to levels comparable to
      septic patients but did not differ among IgAN sub-groups. In contrast, urinary
      C3a and C5a increased significantly and correlated positively with renal
      pathological grades. CONCLUSIONS: In patients with IgAN, urinary and renal C3a
      and C5a and renal expression of C3aR and C5aR are significantly correlated with
      the activity and severity of renal injury. This observation warrants further
      study into the roles of C3a, C5a and their receptors in the pathogenesis of IgAN
      and as potential therapeutic targets.

PMID- 24327136
TI  - Introduction to the special section on Lesbian, Gay, Bisexual, and Transgender
      (LGBT) health disparities: where we are and where we're going.

PMID- 24327135
TI  - A longitudinal study of the effects of instrumental and emotional social support
      on physical activity in underserved adolescents in the ACT trial.
AB  - BACKGROUND: Few previous studies have examined the influence of instrumental and
      emotional social support on physical activity (PA) longitudinally in underserved
      adolescents. PURPOSE: This longitudinal study was a secondary analysis of the
      Active by Choice Today (ACT) trial examining whether instrumental social support
      predicts increases in PA in underserved adolescents, above and beyond emotional
      social support provided by family or peers. METHODS: Students in the sixth grade
      (N = 1,422, 73 % African American, 54 % female, M age = 11 years) in the ACT
      trial participated. At baseline and 19 weeks, previously validated measures of
      social support (family instrumental, family emotional, and peer emotional) were
      completed and moderate-to-vigorous PA (MVPA) was assessed using 7-day
      accelerometry estimates. RESULTS: A mixed ANCOVA demonstrated that baseline (p =
      0.02) and change in family instrumental support (p = 0.01), but not emotional
      support from family or peers, predicted increases in MVPA across a 19-week
      period. CONCLUSIONS: Future interventions in underserved adolescents should
      enhance opportunities for instrumental support for PA.

PMID- 24327137
TI  - [Mutation analysis of EXT genes in two pedigrees with hereditary multiple
      exostoses].
AB  - OBJECTIVE: To detect the underlying genetic defect in two Chinese families with
      hereditary multiple exostoses and provide genetic counseling. METHODS: Potential
      mutations in EXT1 and EXT2 genes in the probands were detected by direct
      sequencing of PCR-amplified exons. Suspected mutations were verified in all
      available family members and 200 unrelated healthy controls. RESULTS: A
      heterozygous frameshift mutation c.346_356delinsTAT in exon 1 of EXT1 and a
      heterozygous deletion mutation c.2009-2012del(TCAA) in exon 10 of EXT1 were
      respectively detected in affected members from the two families. The same
      mutations were not detected in unaffected members and 200 unrelated healthy
      controls. No mutations in EXT2 were detected in the two families. CONCLUSION: Two
      novel mutations of EXT1 have been detected in association with hereditary
      multiple exostoses in two Chinese families. Above results have provided a basis
      for genetic counseling for the two families and expanded the spectrum of EXT1
      mutations.

PMID- 24327138
TI  - [Genetic diagnosis for a Chinese Han family with hereditary multiple
      osteochondromas].
AB  - OBJECTIVE: To identify the genetic cause for a Chinese Han family affected with
      hereditary multiple osteochondromas. METHODS: Two patients, five unaffected
      relatives of the family and 100 unrelated healthy controls were collected. The
      coding sequences and intron/exon boundaries of EXT1 gene were amplified with
      polymerase chain reaction (PCR) and sequenced. RESULTS: A heterozygous c.600G>A
      (p.Trp200X) mutation in exon 1 of the EXT1 gene was detected in the patients. The
      same mutation was not found in unaffected family members and 100 healthy
      controls. CONCLUSION: The hereditary multiple osteochondromas in the family is
      caused by a nonsense mutation (p.Trp200X) in the EXT1 gene.

PMID- 24327139
TI  - [Clinical investigation and mutation analysis of a child with citrin deficiency
      complicated with purpura, convulsive seizures and methioninemia].
AB  - OBJECTIVE: To analyze the clinical features and SLC25A13 gene mutations of a
      child with citrin deficiency complicated with purpura, convulsive seizures and
      methioninemia. METHODS: The patient was subjected to physical examination and
      routine laboratory tests. Blood amino acids and acylcarnitines, and urine organic
      acids and galactose were analyzed respectively with tandem mass spectrometry and
      gas chromatographic mass spectrometry. SLC25A13 gene mutation screening was
      conducted by high resolution melt (HRM) analysis. RESULTS: The petechiae on the
      patient's face and platelet count (27*10(9)/L, reference range 100*10(9)/L
      300*10(9)/L) supported the diagnosis of immunologic thrombocytopenic purpura
      (ITP). Laboratory tests found that the patient have abnormal coagulation, cardiac
      enzyme, liver function and liver enzymes dysfunction. Tandem mass spectrometry
      also found methionine to be increased (286 MUmol/L, reference ranges 8-35
      MUmol/L). The patient did not manifest any galactosemia, citrullinemia and
      tyrosinemia. Analysis of SLC25A13 gene mutation found that the patient has
      carried IVS16ins3kb, in addition with abnormal HRM result for exon 6. Direct
      sequencing of exon 6 revealed a novel mutation c.495delA. The same mutation was
      not detected in 100 unrelated healthy controls. Further analysis of her family
      has confirmed that the c.495delA mutation has derived from her farther, and that
      the IVS16ins3kb was derived from her mother. CONCLUSION: The clinical features
      and metabolic spectrum of citrin deficiency can be variable. The poor prognosis
      and severity of clinical symptoms of the patient may be attributed to the novel
      c.495delA mutation.

PMID- 24327140
TI  - [Mutation analysis for a Chinese family featuring X-linked alpha
      thalassemia/mental retardation syndrome].
AB  - OBJECTIVE: To identify potential mutation in a Chinese family featuring X-linked
      alpha thalassemia/mental retardation syndrome (ATR-X). METHODS: Based on clinical
      symptoms and inheritance pattern, linkage analysis of X chromosome short tandem
      repeats (X-STR) loci was carried out to locate the candidate gene. Subsequently,
      sequences of exons and exon-intron boundaries of the candidate gene were
      amplified with polymerase chain reaction (PCR). Potential mutations were detected
      by direct DNA sequencing. All patients were also analyzed for the trait of
      thalassemia. RESULTS: Linkage analysis indicated the candidate gene to be ATRX.
      Subsequently, a homozygous missense mutation c.736C>T (p.R246C) was found in exon
      9 of ATRX in all of the 3 patients. And a heterozygous mutation c.736C>T
      (p.R246C) was also identified in the patient's mother and grandmother. Similar
      mutations were not detected in other members of the family. Alpha thalassemia was
      detected in the proband and another patient, whose genotypes were determined as 
      alpha(3.7)/alphaalpha and --(sea)/alphaalpha, respectively. CONCLUSION: Missense
      mutation of c.736C>T in ATRX gene is a mutation hotspot, and p.R246C may disturb
      the function of ATRX-DNMT3-DNMT3L domain (ADD), which may be responsible for the
      disease in this family.

PMID- 24327141
TI  - [Clinical and genetic analysis of a Chinese family affected with X-linked Charcot
      Marie-Tooth disease].
AB  - OBJECTIVE: To study the clinical manifestations and identify causative mutations
      for a Chinese family affected with X-linked Charcot-Marie-Tooth disease. METHODS:
      Clinical, electrophysiological and pathological features of the family were
      carefully analyzed by neurologists. Blood samples were obtained from the proband
      and other family members. Genomic DNA was extracted. Mutation analysis of GJB1
      gene was analyzed with PCR and direct sequencing. RESULTS: The family has fit
      with X-linked inheritance, and the affected individuals have typical clinical
      manifestations. A c.614A>G (p.Asn205Ser) mutation was detected in the GJB1 gene
      in all affected individuals in the family. CONCLUSION: A c.614A>G (p.Asn205Ser)
      mutation of GJB1 gene is co-segregated with the disease phenotype in this family
      and probably underlies the disease.

PMID- 24327142
TI  - [Clinical features and mutation analysis of CHRNA4 gene for families and sporadic
      cases affected with autosomal dominant nocturnal frontal lobe epilepsy].
AB  - OBJECTIVE: To investigate mutations of CHRNA4 gene in Chinese patients with
      autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). METHODS: Two hundred
      and fifty-seven patients (including 215 sporadic and 42 familial cases) were
      analyzed. Mutational screening was performed by sequencing all of the 6 exons of
      the CHRNA4 gene including the donor and acceptor splice sites. RESULTS: The
      results have excluded the involvement of any known mutations of the CHRNA4 gene.
      A novel synonymous mutation c.570C>T(D190D) and 6 single nucleotide polymorphisms
      (SNPs) of the CHRNA4 gene were detected in 6 sporadic cases, including c.639T/C,
      c.678T/C, c.1209G/T, c.1227T/C, c.1659G/A, and c.1629C/T. The SNP D190D was
      hererozygous and absent in 200 healthy controls. CONCLUSION: This results
      suggested that mutations of the CHRNA4 gene may be rare in southern Chinese
      population with ADNFLE. The synonymous mutation D190D has not been reported
      previously. Its impact on the pathogenesis of ADNFLE warrant further study.

PMID- 24327143
TI  - [Unbalanced subtelomic rearrangement involving 9q and 22q in a child with mental
      retardation and multiple congenital anomalies].
AB  - OBJECTIVE: To determine genetic cause for a patient with development delay and
      multiple congenital anomalies. METHODS: Routine karyotype analysis was performed
      for the patient and his parents. Array comparative genomic hybridization (array
      CGH) was performed for the patient to detect cryptic chromosome aberration.
      RESULTS: Karyotype analysis revealed no obvious anomaly for the patient and his
      parents. Array CGH has detected a 2.8 Mb heterozygous deletion at 9q34.3 and an
      8.1 Mb heterozygous duplication at 22q. Fluorescence in situ hybridization
      analysis of the patient revealed an unbalanced subtelomeric translocation 46, XY,
      der(9) t(9; 22) (q34.3; q13.2q13.33) mat, which has resulted in partial trisomy
      22q and partial monosomy 9q. Clinical features of the patient included
      developmental delay, facial dysmorphism and multiple congenital anomalies. Upon
      subsequent pregnancy, FISH analysis revealed that the fetus has inherited the
      normal chromosomes 9 and 22 from his mother. Postnatal follow-up confirmed normal
      development milestone and physiques in the child. CONCLUSION: An unbalanced
      translocation involving 9q and 22q has been found in a child featuring multiple
      congenital anomalies, which is due to a balanced translocation 9; 22 in his
      mother. Array CGH and FISH have also helped with discovery of subtelomeric
      rearrangement. Prenatal diagnosis of this aberration in subsequent pregnancies
      with FISH can prevent the recurrence of this disease.

PMID- 24327144
TI  - [Carrier screening for spinal muscular atrophy in 4719 pregnant women in Shanghai
      region].
AB  - OBJECTIVE: Spinal muscular atrophy (SMA) is a common and fatal autosomal
      recessive disorder. Approximately 94% of SMA patients are caused by homozygous
      deletion of SMN1 gene. SMA carrier screening is recommended considering the high
      carrier frequency (1 in 35-50) as well as severity of the disease. METHODS: A
      prospective population-based cohort study was carried out on 4719 pregnant women
      from Shanghai region. Copy numbers of SMN1 and SMN2 genes were effectively
      determined with denaturing high performance liquid chromatography (DHPLC)
      technique. The method has detected 94% of SMA cases with deletion or conversion
      of the SMN1 genes. RESULTS: Ninety SMA carriers with only one copy of the SMN1
      gene were identified among the 4719 pregnant woman. The carrier rate was 1.9%.
      Respectively, 1.2% and 0.6% of the carriers were caused by SMN1 gene deletion and
      SMN1 gene conversion. CONCLUSION: Through this study, we have determined the
      frequency of SMA mutation carriers in a population of pregnant women. The result
      may provide a basis for genetic counseling in order to reduce the rate of SMA
      affected births.

PMID- 24327145
TI  - [In vitro expression study of novel mutations in phenylalanine hydroxylase gene].
AB  - OBJECTIVE: To study the in vitro expression of 6 novel missense mutations (R270G,
      P275A, F121L, A156P, E183G, I324N) and a previously described R408Q mutation of
      phenylalanine hydroxylase (PAH) gene and explore the genotype-phenotype
      correlation through comparison of protein levels and residual enzyme activities.
      METHODS: Seven expression vectors containing PAH cDNA were constructed with a
      site-directed mutagenesis kit. The plasmids were extracted and sequenced to
      confirm the target mutations. pcDNA3.0 containing PAH cDNA was transfected into
      COS-7 cells and total proteins were extracted 48 h after transfection. The
      quantities of proteins and residual enzyme activities of the 7 mutants were
      assessed with the wild-type PAH gene as reference. RESULTS: Relative quantities
      of PAH proteins for R270G, P275A, F121L, A156P, E183G, I324N and R408Q were
      10.5%, 56.6%, 54.3%, 8.7%, 8.5%, 67.3% and 85.4%, respectively. The residual
      enzyme activities were 7.7%, 27.6%, 19.0%, 10.4%, 9.1%, 50.6% and 40.2%,
      respectively. CONCLUSION: PAH residual enzyme activities of 7 PAH mutants were
      all significantly reduced.

PMID- 24327146
TI  - [Methylation pattern of imprinted genes H19 and IGF2r in spermatogenic cells
      cultured in vitro].
AB  - OBJECTIVE: To compare the methylation patterns of imprinting control region (ICR)
      of H19 gene and differentially methylated region (DMR) of IGF2r gene in mature
      sperms derived from epididymis of Kunming mice and in vitro cultured haploid
      spermatids. METHODS: The H19 ICR and IGF2r DMR2 were detected by bisulfite
      sequencing PCR (BSP). The results were compared with standard sequence derived
      from GenBank using a DNAman software. RESULTS: 96.67% (15 CpG sites) of H19 ICR
      was found to be methylated, and 94.29% IGF2r DMR2 was found to be unmethylated in
      mature sperms. By contrast, 69.33% of H19 ICR and 44.29% of IGF2r DMR2 were found
      to be methylated in the haploid spermatids cultured in vitro. A significant
      difference was detected in the methylation patterns between the two types of
      cells (P<0.01). CONCLUSION: The H19 ICR in mature sperm of Kunming mice was
      essentially methylated, while the IGF2r DMR2 was essentially unmethylated.
      Partial methylation loss in H19 ICR and abnormal methylation in IGF2r DMR2 were
      found in the haploid spermatids cultured in vitro.

PMID- 24327147
TI  - [MicroRNAs and polyglutamine diseases].
AB  - Polyglutamine(PolyQ) diseases comprise a group of inherited neurodegenerative
      disorders with significant clinical and genetic heterogeneity. Although they
      share a common mechanism involving dynamic expansion of CAG trinucleotide
      repeats, their clinical features may vary and there has been no specific
      treatment. Recently, much attention had been attracted to microRNAs which, as a
      new type of posttranscription regulatory factor, have proven to significantly
      affect the progress of PolyQ disease. This review will focus on the roles of
      microRNAs in the pathogenesis of PolyQ diseases and their potential use for
      therapy. 

PMID- 24327148
TI  - [Research on molecular markers for epigenetic changes in myeloid malignancies].
AB  - Novel recurrent somatic mutations have been identified in patients with myeloid
      malignancies including myeloproliferative neoplasms (MPNs), myelodysplastic
      syndrome (MDS) and acute myeloid leukaemia (AML). Mutations of tet methylcytosine
      dioxygenase 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase
      (IDH)1/2, enhancer of zeste homologue 2 (EZH2) and additional sex combs-like 1
      (ASXL1) have been shown to play important roles in the regulation of epigenetic
      patterning, and may be used as molecular predictors for pathogenesis and clinical
      outcome for patients with myeloid malignancies. 

PMID- 24327149
TI  - [Association of RNASET2 gene polymorphisms and haplotypes with Graves disease in
      Han Chinese population from coastal regions of Shandong].
AB  - OBJECTIVE: To assess the association of RNASET2 gene polymorphisms and haplotypes
      with Graves disease (GD) in Han Chinese population from coastal regions of
      Shandong Province. METHODS: A total of 471 GD patients and 472 controls were
      enrolled. Genotypes of single nucleotide polymorphisms (SNPs) in RNASET2 gene
      were determined with a Taqman probe on a Fluidigm EPl platform. Haplotypes and
      their frequencies were analyzed with a SHEsis online software. RESULTS: There was
      a significant difference in allele frequencies of rs3777722, rs3777723 and
      rs9355610 between the GD patients and the controls (P=0.018; P=0.028;
      P=0.021).Allele frequencies of rs3777722 and rs9355610 were significantly lower
      in GD than in the controls (P=0.018, P=0.021). Haplotypes A-A-C-A and A-A-T-A
      were significantly more common in the control group compared with the GD group
      (P=0.046, OR=0.448, 95%CI:0.200-1.006; P=0.049, OR=0.823, 95%CI:0.678-0.999). The
      frequency of C-G-C-G haplotype was significantly higher in GD patient group than
      the control group (P=0.018). CONCLUSION: RNASET2 gene polymorphisms and
      haplotypes are associated with GD in Han population from coastal areas of
      Shandong Province. rs3777722 and rs9355610 may contribute to the risk for GD.

PMID- 24327150
TI  - [A study of HLA-DPA1 and DPB1 matching status for unrelated donor-recipient pairs
      matched at allele level for HLA-A, -B, -C, -DRB1 and -DQB1 loci].
AB  - OBJECTIVE: To analyze the status of HLA-DPA1 and DPB1 matching for unrelated
      donor-recipient pairs matched at high-resolution allele level for HLA-A, B, C,
      DRB1 and DQB1 loci. METHODS: A total of 76 unrelated donor-recipient pairs
      matching at allele level for HLA-A, B, C, DRB1 and DQB1 loci were subjected to
      HLA-DPA1 and DPB1 sequence-based typing (SBT). HLA-DPA1and DPB1 matching status
      at high-resolution allelic level was also analyzed. RESULTS: The allelic identity
      ratio for single HLA-DPA1 and DPB1 were 17.1% and 9.2%, respectively. HLA-DPA1
      and DPB1 allelic identity ratio were both very low. The majority of unrelated
      donor-recipient pairs (73.7%) had an incompatibility at 1 HLA-DPA1 allele, 9.2%
      of pairs had an incompatibility at 2 DPA1 alleles. As for the high-polymorphic
      HLA-DPB1 gene, 57.9% of studied donor-recipient pairs had an incompatibility at 1
      HLA-DPB1 allele, almost 1/3 (32.9%) of them were completely incompatible. When
      HLA-DPA1 and DPB1 genes were analyzed together, the donor-recipient pairs matched
      at 2/4 was the most common (51.4%), 4/4 allelic complete matched pairs accounted
      for 5.6%, and 0/4 matched pairs accounted for 8.3%. CONCLUSION: Our results
      indicated that the ratio of HLA-DPA1 and DPB1 complete match in the unrelated
      donor-recipient pairs matching at allelic level for HLA-A, B, C, DRB1 and DQB1
      loci were very low. The effect of HLA-DPA1 and DPB1 matching status on clinical
      unrelated stem cell transplantation still needs to be elucidated.

PMID- 24327151
TI  - [Study on KIR gene polymorphisms in 416 renal transplantation recipients from
      southern Zhejiang].
AB  - OBJECTIVE: To investigate polymorphisms of killer cell immunoglobulin-like
      receptor gene (KIR) in renal transplant recipients from southern Zhejiang.
      METHODS: KIR genotypes were analyzed by PCR-SSP in 416 renal transplant
      recipients, and the genotype frequencies were compared with populations from
      Eastern China and worldwide. RESULTS: All 16 known KIR genes were detected in the
      renal transplant recipients, and KIR2DL4, 3DL2-3, 3PD1 were found in all. As a
      pseudogene, 2DP1 has a high genotype frequency (99%). The frequencies of KIR2DL1,
      2DL3, 3DL1, 2DS4 have ranged from 92.1% to 98.8%. Compared with 11 groups in
      Eastern China and other countries, the KIR2DL2 phenotype frequency was higher
      (34.6%) than those of Shanghai, Zhejiang and Jiangsu populations (P<0.05). Among
      41 genotypes, three have not been reported previously. The most common genotype
      was AA1, with a frequency of 43.51%, which was significantly lower than those of
      Jiangsu and Northern Zhejiang. CONCLUSION: Renal transplant recipients from
      southern Zhejiang share similar features with Eastern China Han population with
      regard to KIR polymorphisms, but also have unique frequencies for KIR genotypes.

PMID- 24327152
TI  - [Association of single nucleotide polymorphism in M-type phospholipase A2
      receptor gene with membranous nephropathy].
AB  - OBJECTIVE: To assess the association between single nucleotide polymorphism in M
      type phospholipase A2 receptor (PLA2R) gene and membranous nephropathy (MN) in a
      Chinese Han population. METHODS: A total of 430 non-related Chinese Hans were
      enrolled, which included 145 patients with idiopathic membranous nephropathy
      (IMN), 53 patients with secondary MN and 232 normal controls (NC). The
      polymorphism of rs35771982 in PLA2R gene was determined with polymerase chain
      reaction-restriction fragment length polymorphism assay. Serum anti-PLA2R
      antibodies were detected by Western blotting. RESULTS: The genotypic and allelic
      frequencies for rs35771982 was significantly different among the three groups
      (P=0.004; P<0.001). CC genotype and C allele were significantly more common in
      IMN group compared with NC group (P=0.002; P<0.001) or secondary MN group
      (P=0.011; P=0.001). In the IMN group, the CC genotype was correlated with serum
      albumin (Alb), 24-hour urine protein (24h UP) and positive rate of serum anti
      PLA2R antibody (P<0.001, P<0.001, P=0.010), and was a risk factor for IMN
      (OR=8.927, 95%CI:2.107-37.821, P=0.003). CONCLUSION: The CC genotype and C allele
      at rs35771982 in PLA2R gene are associated with susceptibility to IMN in Chinese
      Hans. The associations between CC genotype and severity of IMN as well as serum
      anti-PLA2R antibody have indicated that production of anti-PLA2R autoantibody in
      IMN patients is associated with mutation at the rs35771982 locus of PLA2R gene.

PMID- 24327153
TI  - [Association between matrix metalloproteinase-10 gene polymorphisms and
      instability of carotid plaque].
AB  - OBJECTIVE: To assess the association between 2 single nucleotide polymorphisms
      (SNPs) located in exonic regions of matrix metalloproteinase-10 (MMP-10) gene and
      instability of carotid plaques in a Han Chinese population. METHODS: Five hundred
      and eighty-five patients were divided into carotid vulnerable plaque group
      (n=206) and stable plaque group (n=379) based on results of carotid B-mode
      ultrasonography. The SNPs were genotyped by real-time polymerase chain reaction
      using an ABI 7300 TaqMan platform. RESULTS: The distribution of rs17435959
      between the two groups was significantly different at both genotypic (GC+CC vs.
      GG, P=0.006, OR=2.012) and allelic levels (C vs. G, P=0.001,OR=2.160). Above
      differences have remained significant with binary logistic regression analysis
      (P=0.007, OR=2.022; P=0.002, OR=2.104). The minor allele frequency of rs17293607
      was 0.56%. CONCLUSION: Above findings suggested that rs17435959 of the MMP-10
      gene is associated with carotid vulnerable plaque in ethnic Chinese Hans. The C
      allele may be a susceptible predictor for carotid vulnerable plaque.

PMID- 24327154
TI  - [Association study of PRDM16 gene polymorphisms with essential hypertension in
      Xinjiang Uygur population].
AB  - OBJECTIVE: To assess the association of polymorphisms of PR domain containing 16
      gene (PRDM16) with essential hypertension in ethnic Uygur population from
      Xinjiang, China. METHODS: Functional regions of the PRDM16 gene were sequenced in
      48 Uygur subjects with essential hypertension selected from 480 hypertensive
      patients and 819 normotensive controls. Representative variations were genotyped
      with TaqMan-PCR method. Association of variations of PRDM16 gene with
      hypertension was analyzed. RESULTS: For the 4 genotyped representative variations
      (rs2236518, rs2282198, rs2493292 and rs870171), no significant difference in
      genotype distribution and allele frequencies has been found between the patient
      and control groups (P>0.05). By ANOVA analysis, none of the polymorphisms was
      significantly associated with systolic or diastolic blood pressure (P>0.05). Nor
      was significant difference in haplotypic frequencies between the two groups
      detected (P>0.05). CONCLUSION: We have found no association between the four
      polymorphisms (rs2236518, rs2282198, rs2493292 and rs870171) of the PRDM16 gene
      with essential hypertension in ethnic Uygur population from Xinjiang.

PMID- 24327155
TI  - [Detection of hemophilia A carrier by FVIII:C/vWFAg ratio].
AB  - OBJECTIVE: To determine the cut-off value for coagulation factor VIII activity
      (FVIII:C) to von Willebrand factor antigen (vWFAg) ratio which can classify
      obligatory carriers of hemophilia A and normal females, and assess its
      feasibility to diagnose suspected carriers in affected families through
      comparison with the method of gene diagnosis. METHODS: FVIII:C assay was carried
      out by a one-stage method in both obligatory carriers and normal females. vWF
      antigen was measured with ELISA assay. The FVIII:C/vWF ratio was calculated.
      Statistic analysis was carried out to determine the cut-off value which can
      classify the two groups. The ratio was then used to diagnose suspected carriers
      from families affected with hemophilia A. The results were compared with that by
      long distance polymerase chain reaction, genetic linkage analysis and/or direct
      sequencing. RESULTS: The FVIII:C/vWFAg value for 90.6% of obligatory carriers was
      under 0.82. Should 0.82 be selected as the cut-off value to diagnose the 42
      suspected carriers, most of them can be readily diagnosed. The results were all
      in agreement with that of genetic analysis. CONCLUSION: Cut-off value of
      FVIII:C/vWFAg may be used for initial diagnose of the suspected carriers from
      families affected with hemophilia A. The method is quite convenient and reliable.

PMID- 24327156
TI  - [Association of interleukin 10 gene -592C/A polymorphism with coronary artery
      disease].
AB  - OBJECTIVE: To assess the association of interleukin 10 (IL10) gene -592C/A
      polymorphism with morbidity of coronary heart disease in a southern Chinese Han
      population. METHODS: Frequencies of various genotypes and alleles for the IL10 
      592C/A polymorphism (rs1800872) were determined by the means of matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in
      249 patients and 132 unaffected controls. RESULTS: The frequencies of both IL10 
      592C/A site and different alleles have reached statistical significance (P<0.05)
      after correcting the difference in clinical data by logistic regression analysis.
      The risk of coronary heart disease in the patients with A gene (AA+CA) was 2.449
      times greater than those without (95%CI:1.214-4.940, P=0.012). CONCLUSION: IL10
      gene -592C/A polymorphism is associated with the risk of coronary heart disease.
      Allele A may be a risk factor for this disease in the studied population.

PMID- 24327157
TI  - [Association of CFTR gene polymorphism with congenital bilateral absence of vas
      deferens in ethnic Han Chinese patients].
AB  - OBJECTIVE: To assess the association between a 5T polymorphism in intron 8 of
      cystic fibrosis transmembrane conductance regulator (CFTR) gene and congenital
      bilateral absence of vas deferens (CBAVD) in Han Chinese males. METHODS: Genomic
      DNA from 33 individuals with CBAVD and 99 azoospermic males with CBAVD were
      recruited. The 5T polymorphism was detected with PCR, TA cloned and sequenced.
      RESULTS: CFTR gene mutations were identified in 17 (51.5%) of patients with
      CBAVD. In 3 patients (17.6%), the mutations were identified on both alleles. Nine
      CFTR gene mutations (9.1%) were detected in 99 azoospermic patients, for whom
      none had mutations on both alleles. CONCLUSION: This study has confirmed
      molecular heterogeneity of CFTR mutations in CBAVD. For CBAVD patients without 5T
      mutations, other changes may be found in the same gene.

PMID- 24327158
TI  - [Molecular genetic analysis of two individuals with Bw subtypes of ABO variant].
AB  - OBJECTIVE: To investigate the molecular characteristics of Bw subgroup of ABO
      variant. METHODS: Two individuals with Bw phenotypes were confirmed by standard
      serological assays. ABO genotype was analyzed with polymerase chain reaction
      sequence specific primer (PCR-SSP) method. Exons 6-7 of B genes were amplified by
      specific PCR, and the PCR product was subjected to direct sequencing. RESULTS:
      The probands were identified as Bw phenotype by serological assays. As detected
      by PCR-SSP, the genotypes of the two probands were both B/O2. Compared with the
      wild-type B101, the B allele in one individual has harbored a missense mutation
      (C721T) in exon 7, which resulted in an amino acid substitutions (R241S). In the
      second individual, the B allele has harbored a missense mutation (C278T) in exon
      6, which also resulted in an amino acid substitution (P93L). CONCLUSION: A Bw03
      allele and a Bw12 allele were identified, which resulted in varied intensity of B
      antigen expression.

PMID- 24327159
TI  - [Pedigree investigation and genetic analysis of a case with p blood group].
AB  - OBJECTIVE: To explore the molecule basis of a p blood group in a patient with
      gastric carcinoma. METHODS: The p phenotype was determined with serological
      method. Inheritance of the p phenotype was investigated by pedigree analysis.
      Sequence of alpha-1,4- galactosyltransferase (A4GALT) gene was determined by
      Sanger method. RESULTS: The proband and his younger brother were both determined
      to have a p phenotype. Two homozygous variations, c.343A>T (AAA>TAA) and c.903C>G
      (CCC>CCG), have been detected in exon 3 of the A4GALT gene. Among these, c.343
      A>T (AAA>TAA) was a novel mutation, which has resulted in a termination codon,
      with which no normal product of the gene can be produced. c.903C>G was determined
      to be a polymorphism. CONCLUSION: A novel c.343A>T mutation in the A4GALT gene
      probably underlies the p phenotype, to which a Genbank access number KC202808 has
      been assigned.

PMID- 24327160
TI  - [Genetic polymorphisms of 10 short tandem repeat loci in Lhasa Tibetans in
      China].
AB  - OBJECTIVE: To investigate genetic polymorphisms of 10 short tandem repeats loci
      (D6S1043, D7S3048, D9S925, D10S2325, D11S2368, D14S608, D15S659, D17S1290,
      D20S470 and GATA198B05) in Tibetans from Lhasa, China. METHODS: Following
      extraction, DNA from 208 unrelated Tibetan individuals was amplified with a self
      designed multiplex PCR system. The amplified fragments were separated by
      electrophoresis on an ABI 3130 Genetic Analyzer and analyzed with
      GeneMapper(r)3.2 software. RESULTS: The distributions of genotype for the 10 STR
      loci in the population were in accordance with Hardy-Weinberg equilibrium. The
      polymorphism information component for the 10 loci was 0.750-0.860, the degree of
      heterozygosity was 0.726-0.865, the discrimination power was 0.919-0.968, and the
      probability of exclusion was 0.470-0.725. The combined probability of exclusion
      and combined discrimination power was 0.9998 and 0.999 999 999 997, respectively.
      CONCLUSION: Above STR loci have high probability of exclusion and discrimination
      power, which can be used as candidate markers for population genetic research and
      forensic practice for Tibetans from Lhasa, China.

PMID- 24327161
TI  - [Identification of a rare allele FGA-13 in Guangdong Han population].
AB  - OBJECTIVE: To report on a rare allele FGA-13 identified in Guangdong Han
      population. METHODS: The rare allele was detected by PCR-STR and DNA sequencing.
      RESULTS: The core repeat sequence of rare allele FGA-OL is
      [TTTC]3[TTTT][TTCT][CTTT]5 [CTCC][TTCC]2, which has been determined as FGA-13.
      CONCLUSION: The rare allele FGA-13 is also present in Guangdong Han population.
      This is significant for personal identification and paternity testing.

PMID- 24327164
TI  - The efficacy of rib-based distraction with VEPTR in the treatment of early-onset
      scoliosis in patients with arthrogryposis.
AB  - BACKGROUND: Although arthrogryposis multiplex congenital (AMC) is a rare
      condition, rapidly progressive scoliosis is common in children with AMC. Only a
      limited number of studies characterize the nature of these curves, and even fewer
      describe surgical outcomes. To determine efficacy or rib-based distraction in
      these patients, we reviewed the outcomes of the use of the Vertical Expandable
      Prosthetic Titanium Rib (VEPTR) device in what we believe is the first study to
      report this. METHODS: Search of the Chest Wall Spinal Deformity Study Group
      database identified 10 children with AMC and early-onset scoliosis who were
      treated with the VEPTR device at 6 different pediatric health centers. The 7
      female and 3 male patients had their initial surgery at an average age of 5
      years. Mean follow-up was 4.2 years. RESULTS: The most common curve was from T5
      to L2. After initial VEPTR insertion, the scoliosis decreased from a mean of 67
      to 43 degrees (37% correction) and kyphosis from 65 to 48 degrees (29%
      correction). The mean proximal junctional kyphosis after initial insertion was 33
      degrees. At final follow-up, scoliosis and kyphosis were 55 degrees (17%
      correction) and 62 degrees (8% correction), respectively. Spinal growth during
      the treatment period showed a mean T1-S1 increase of 4.2 cm or approximately 1
      cm/y. In the 62 procedures performed over the course of the study period, 6
      complications occurred in 4 patients: 3 infections, 2 rib failures, and 1 implant
      failure. Six patients had proximal junctional kyphosis of >=45 degrees at the
      last follow-up. CONCLUSIONS: In children with AMC, rib-based distraction using
      the VEPTR is an effective treatment method for controlling scoliosis and kyphosis
      and maintaining thoracic growth, but proximal junctional kyphosis remains a
      problem.

PMID- 24327165
TI  - Postoperative spine and VEPTR infections in children: a case-control study.
AB  - BACKGROUND: Surgical site infection (SSI) after pediatric scoliosis surgery is a
      major cause of morbidity. We compared the odds ratios of various potential risk
      factors for infection among patients who developed a deep SSI following spinal
      deformity surgery and those who remained infection free. METHODS: This was a case
      control study, not a matched study. More noninfection cases (50) than infection
      cases (20) were selected because more were available. Twenty children with a deep
      SSI after scoliosis surgery were compared with 50 similar children who did not
      develop a deep SSI. Fourteen perioperative factors were examined in both the
      groups. RESULTS: Of the 20 patients who had a deep SSI, 14 had neuromuscular
      scoliosis. In the infected group, 6 patients had undergone vertical expandable
      prosthetic titanium rib placement, 2 had undergone growing rod insertion, and 12
      had undergone posterior spinal fusion. Eighteen patients developed a SSI within 1
      year of the operation and 2 patients presented with a SSI >1 year after surgery.
      Sixteen patients had positive cultures. Majority were skin flora: coagulase
      negative Staphylococcus (8) and Propionibacterium acnes (4). Both patients with
      tracheostomies had Enterococcus faecalis infections. When comparing the 20
      patients with deep SSI to the 50 controls, increased preoperative Cobb angle
      (P=0.011), increased postoperative Cobb angle (P=0.0043), nonambulatory status
      (P=0.0002), and increased length of stay (P=0.015) were associated with
      significantly increased odds of infection. CONCLUSIONS: Our study shows that
      patients with neuromuscular scoliosis are at higher risk of developing a deep SSI
      after spinal deformity surgery. Skin flora is a common cause of deep SSI. We have
      now instituted a standard skin preparation protocol to include alcohol and
      chlorhexidine washes the night before and the morning of surgery. We have altered
      our prophylactic antibiotic regimen to cover skin flora in all patients and
      gastrointestinal flora in patients with a tracheostomy. We have counseled the
      families of nonambulatory children with large neuromuscular curves regarding the
      significantly increased odds of postoperative deep SSI. LEVEL OF EVIDENCE: Level
      III.

PMID- 24327166
TI  - Bier block regional anesthesia and casting for forearm fractures: safety in the
      pediatric emergency department setting.
AB  - BACKGROUND: Bier block regional anesthesia was first described in 1908; however,
      it is uncommonly used for fears of cardiac and neurological complications.
      Although recent studies have documented safe usage in an adult population, no
      study to date has investigated its use in a pediatric setting. In addition, most
      emergency departments feel that splint placement is safer than casting after
      acute forearm fracture reduction in the pediatric population. However, to our
      knowledge there is no such study that documents the complication rates associated
      with immediate casting. The goal of this study was to assess the safety and
      efficacy of Bier block regional anesthesia and immediate cast application after
      closed reduction of pediatric forearm fractures. METHODS: A retrospective review
      was conducted of patients treated for forearm fractures in a 2-year period at a
      major metropolitan pediatric hospital. Rates of complications and length and
      costs of the 2 procedures were analyzed. RESULTS: A total of 600 patients were
      treated with Bier block regional anesthesia and 645 were treated with conscious
      sedation for displaced fractures of the forearm in the 2-year study period. No
      complications requiring admission were seen in either group. No patient
      experienced compartment syndrome or a need for readmission secondary to cast
      application. 2.2% and 4.3% (P=0.0382) of patients in the Bier block and sedation
      groups, respectively, needed their cast bivalved secondary to swelling. The
      average time from initiation of procedural sedation to discharge was 1 hour and
      42 minutes, whereas the time to discharge from initiation of Bier block regional
      anesthesia was 47 minutes (P<0.0001). The average cost for a patient treated with
      procedural sedation was $6313, whereas the average cost for the Bier block
      regional anesthesia group was $4956. CONCLUSIONS: Bier block regional anesthesia
      is a safe, efficient, and cost-effective method of reducing pediatric forearm
      fractures. Immediate cast application can be used without fear of major
      complications. LEVELS OF EVIDENCE: Level III--retrospective review.

PMID- 24327167
TI  - Towards the estimation of effect measures in studies using respondent-driven
      sampling.
AB  - Respondent-driven sampling (RDS) is an increasingly common sampling technique to
      recruit hidden populations. Statistical methods for RDS are not straightforward
      due to the correlation between individual outcomes and subject weighting; thus,
      analyses are typically limited to estimation of population proportions. This
      manuscript applies the method of variance estimates recovery (MOVER) to construct
      confidence intervals for effect measures such as risk difference (difference of
      proportions) or relative risk in studies using RDS. To illustrate the approach,
      MOVER is used to construct confidence intervals for differences in the prevalence
      of demographic characteristics between an RDS study and convenience study of
      injection drug users. MOVER is then applied to obtain a confidence interval for
      the relative risk between education levels and HIV seropositivity and current
      infection with syphilis, respectively. This approach provides a simple method to
      construct confidence intervals for effect measures in RDS studies. Since it only
      relies on a proportion and appropriate confidence limits, it can also be applied
      to previously published manuscripts. 

PMID- 24327168
TI  - Analytical methods for the evaluation of melamine contamination.
AB  - There is an urgent need for the analysis of melamine in the global pharmaceutical
      supply chain to detect economically motivated adulteration or unintentional
      contamination using a simple, nondestructive analytical technique that confirms
      the extent of adulteration in a shorter time period. In this work, different
      analytical techniques (thermal analysis, X-ray diffraction, Fourier transform
      infrared (FT-IR), FT-Raman, and near-infrared (NIR) spectroscopy) were evaluated
      for their ability to detect a range of melamine levels in gelatin. While FT-IR
      and FT-Raman provided qualitative assessment of melamine contamination or
      adulteration, powder X-ray diffraction and NIR were able to detect and quantify
      the presence of melamine at levels as low as 1.0% w/w. Multivariate analysis of
      the NIR data yielded the most accurate model when three principal components were
      used. Data were pretreated using standard normal variate transformation to remove
      multiplicative interferences of scatter and particle size. The model had a root
      mean-square error of calibration of 2.4 (R(2) = 0.99) and root-mean square error
      of prediction of 2.5 (R(2) = 0.96). The value of the paired t test for actual and
      predicted samples (1%-50% w/w) was 0.448 (p < 0.05), further indicating the
      robustness of the model.

PMID- 24327169
TI  - Expression of the rodent-specific alternative splice variant of tryptophanyl-tRNA
      synthetase in murine tissues and cells.
AB  - Tryptophanyl-tRNA synthetase (TrpRS) catalyzes the aminoacylation of tRNA(Trp).
      mRNA of a rodent-specific alternative splice variant of TrpRS (SV-TrpRS), which
      results in the inclusion of an additional hexapeptide at the C-terminus of full
      length TrpRS (FL-TrpRS), has been identified in murine embryonic stem (ES) cells.
      In the present study, we evaluated the expression of mouse TrpRS mRNA by real
      time reverse transcription PCR. We show that SV-TrpRS and FL-TrpRS mRNAs are
      highly expressed in murine ES cells, embryo, spleen, lung, liver and uterus, and
      that the relative expression of SV-TrpRS compared to FL-TrpRS is significantly
      less in the brain. Moreover, we found that interferon-gamma increases the
      expression of TrpRS in a mouse cell line. These results provide the first
      evidence for tissue-specific expression and alternative splicing of mouse TrpRS. 

PMID- 24327170
TI  - Abomasal infusion of arginine stimulates SCD and C/EBPbeta gene expression, and
      decreases CPT1beta gene expression in bovine adipose tissue independent of
      conjugated linoleic acid.
AB  - Based on previous research with bovine peadipocytes, we hypothesized that
      infusion of arginine into the abomasum of Angus steers stimulates stearoyl-CoA
      desaturase (SCD) gene expression in bovine subcutaneous (s.c.) adipose tissue,
      and that this would be attenuated by conjugated linoleic acid (CLA). Growing
      Angus steers were infused abomasally with L-arginine 50 g/day; n = 13; provided
      as L-arginine HCl) or L-alanine (isonitrogenous control, 100 g/day; n = 11) for
      14 days. For the subsequent 14 days, half of the steers in each amino acid group
      were infused with CLA (100 g/day). Body weight gain and average daily gain were
      unaffected (P > 0.15) by infusion of arginine or CLA into the abomasum. The
      plasma concentrations of cis-9, trans-11 and trans-10, cis-12 CLA were increased
      CLA infusion (P = 0.001) and infusion of arginine increased plasma arginine (P =
      0.01). Compared with day 0, fatty acid synthase, glucose-6-phosphate
      dehydrogenase, and 6-phosphogluconate dehydrogenase enzyme activities in s.c.
      adipose tissue increased by day 14 in steers infused with either alanine or
      arginine (all P < 0.01). NADP-MDH activity was higher (P = 0.01) in steers
      infused with arginine than in steers infused with arginine plus CLA by day 28,
      but lipid synthesis in vitro from glucose and acetate was unaffected by infusion
      of either arginine or CLA (P > 0.40). By day 28, C/EBPbeta and SCD gene
      expression was higher, and CPT1beta gene expression was lower, in s.c. adipose
      tissue of steers infused with arginine than in steers infused with alanine (+/
      CLA) (P = 0.05). CLA decreased adipose tissue oleic acid (18:1n-9) in alanine- or
      arginine-infused steers (P = 0.05), although CLA had no effect on SCD gene
      expression. The data indicate that supplemental arginine promotes adipogenic gene
      expression and may promote lipid accumulation in bovine adipose tissue. L
      Arginine may beneficially improve beef quality for human consumption.

PMID- 24327171
TI  - Gender-related effects on urine L-cystine metastability.
AB  - Cystinuria is an autosomal recessive disease that causes L-cystine precipitation
      in urine and nephrolithiasis. Disease severity is highly variable; it is known,
      however, that cystinuria has a more severe course in males. The aim of this study
      was to compare L-cystine metastability in first-morning urine collected from 24
      normal female and 24 normal male subjects. Samples were buffered at pH 5 and
      loaded with L-cystine (0.4 and 4 mM final concentration) to calculate the amount
      remaining in solution after overnight incubation at 4  degrees C; results were
      expressed as Z scores reflecting the L-cystine solubility in each sample. In
      addition, metabolomic analyses were performed to identify candidate compounds
      that influence L-cystine solubility. L-cystine solubility Z score was +0.44 +/-
      1.1 and -0.44 +/- 0.70 in female and male samples, respectively (p < 0.001).
      Further analyses showed that the L-cystine solubility was independent from urine
      concentration but was significantly associated with low urinary excretion of
      inosine (p = 0.010), vanillylmandelic acid (VMA) (p = 0.015), adenosine (p =
      0.029), and guanosine (p = 0.032). In vitro L-cystine precipitation assays
      confirmed that these molecules induce higher rates of L-cystine precipitation in
      comparison with their corresponding dideoxy molecules, used as controls. In
      silico computational and modeling analyses confirmed higher binding energy of
      these compounds. These data indicate that urinary excretion of nucleosides and
      VMA may represent important factors that modulate L-cystine solubility and may
      represent new targets for therapy in cystinuria.

PMID- 24327172
TI  - Synergistic interaction between redox-active electrolyte and binder-free
      functionalized carbon for ultrahigh supercapacitor performance.
AB  - Development of supercapacitors with high-energy density and high-power density is
      a tremendous challenge. Although the use of conductive carbon materials is
      promising, other methods are needed to reach high cyclability, which cannot be
      achieved by fully utilizing the surface-oxygen redox reactions of carbon. Here we
      introduce an effective strategy that utilizes Cu(2+) reduction with carbon-oxygen
      surface groups of the binder-free electrode in a new redox-active electrolyte. We
      report a 10-fold increase in the voltammetric capacitance (4,700 F g(-1))
      compared with conventional electrolyte. We measured galvanostatic capacitances of
      1,335 F g(-1) with a retention of 99.4% after 5,000 cycles at 60 A g(-1) in a
      three-electrode cell and 1,010 F g(-1) in a two-electrode cell. This improvement
      is attributed to the synergistic effects between surface-oxygen molecules and
      electrolyte ions as well as the low charge transfer resistance (0.04 Omega) of
      the binder-free porous electrode. Our strategy provides a versatile method for
      designing new energy storage devices and is promising for the development of high
      performance supercapacitors for large-scale applications.

PMID- 24327173
TI  - Safety and pharmacokinetics of escalating doses of human recombinant nerve growth
      factor eye drops in a double-masked, randomized clinical trial.
AB  - BACKGROUND AND OBJECTIVES: Nerve growth factor (NGF) is a neurotrophin with
      therapeutic possibilities that extend from the nervous system to the eye. We
      tested the safety, maximal tolerated dose, pharmacokinetics, and antigenicity of
      a novel human recombinant NGF (rhNGF) eye-drop formulation in a phase I study.
      METHODS: This prospective, randomized, double-masked, vehicle-controlled trial,
      sponsored by Dompe SpA (registered as NCT01744704 at ClinicalTrials.gov),
      enrolled 74 healthy volunteers (24 females, 50 males, age 40.2 +/- 11.8 years).
      Subjects were randomized in three cohorts to receive (1) a single eye-drop
      containing 0.0175, 0.175, or 0.7 MUg rhNGF; (2) a single ascending dose of rhNGF
      eye drops three times a day for 1 day (total daily dose 2.1, 6.3, or 18.9 MUg),
      or vehicle; or (3) a multiple ascending dose of rhNGF eye drops three times a day
      for 5 days (total dose 10.5, 31.5, or 94.5 MUg), or vehicle. Outcome measures
      included blood chemistry, urinalyses, vital signs, electrocardiograms (ECGs),
      serum NGF antibodies, ocular and systemic adverse events (AEs), visual acuity,
      tear function, intraocular pressure, fundus oculi, and ocular symptoms. RESULTS:
      Administration of rhNGF eye drops did not result in a significant increase of
      circulating NGF levels and no antidrug antibodies were detected in serum. No
      serious AEs were recorded, and a few mild, transient ocular AEs related to rhNGF
      administration were reported only at the highest concentration. CONCLUSIONS:
      rhNGF eye drops were well tolerated, with no detectable clinical evidence of
      systemic AEs. These results pave the way for the development of clinical trials
      on rhNGF in ophthalmology.

PMID- 24327174
TI  - Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work.
AB  - PURPOSE: We explored whether altered expression of factors tuning mitochondrial
      metabolism contributes to muscular adaptations with endurance training in the
      condition of lowered ambient oxygen concentration (hypoxia) and whether these
      adaptations relate to oxygen transfer as reflected by subsarcolemmal mitochondria
      and oxygen metabolism in muscle. METHODS: Male volunteers completed 30 bicycle
      exercise sessions in normoxia or normobaric hypoxia (4,000 m above sea level) at
      65% of the respective peak aerobic power output. Myoglobin content, basal oxygen
      consumption, and re-oxygenation rates upon reperfusion after 8 min of arterial
      occlusion were measured in vastus muscles by magnetic resonance spectroscopy.
      Biopsies from vastus lateralis muscle, collected pre and post a single exercise
      bout, and training, were assessed for levels of transcripts and proteins being
      associated with mitochondrial metabolism. RESULTS: Hypoxia specifically lowered
      the training-induced expression of markers of respiratory complex II and IV (i.e.
      SDHA and isoform 1 of COX-4; COX4I1) and preserved fibre cross-sectional area.
      Concomitantly, trends (p < 0.10) were found for a hypoxia-specific reduction in
      the basal oxygen consumption rate, and improvements in oxygen repletion, and
      aerobic performance in hypoxia. Repeated exercise in hypoxia promoted the
      biogenesis of subsarcolemmal mitochondria and this was co-related to expression
      of isoform 2 of COX-4 with higher oxygen affinity after single exercise, de
      oxygenation time and myoglobin content (r >= 0.75). Conversely, expression in
      COX4I1 with training correlated negatively with changes of subsarcolemmal
      mitochondria (r < -0.82). CONCLUSION: Hypoxia-modulated adjustments of aerobic
      performance with repeated muscle work are reflected by expressional adaptations
      within the respiratory chain and modified muscle oxygen metabolism.

PMID- 24327176
TI  - Bright ideas.

PMID- 24327177
TI  - Untested waters.

PMID- 24327175
TI  - Glucocorticoids improve high-intensity exercise performance in humans.
AB  - PURPOSE: It was investigated whether oral dexamethasone (DEX) administration
      improves exercise performance by reducing the initial rate of muscle fatigue
      development during dynamic exercise. METHODS: Using a double-blinded placebo
      controlled randomized crossover design, subjects ingested either 2 * 2 mg of DEX
      or placebo for five consecutive days. Muscle function was investigated using one
      legged kicking exercise and whole body performance was evaluated using a 20-m
      shuttle run and a 30-m sprint test. RESULTS: One-legged dynamic knee-extensor
      exercise time to exhaustion was 29 +/- 35% (mean +/- SD) longer (P < 0.05) in DEX
      compared to Placebo. Likewise, total running distance in the shuttle run test was
      19 +/- 23% longer (P < 0.05), whereas 30-m sprint performance was unaltered.
      During the initial 75 s of dynamic leg extensions, peak force and rate of force
      development determined from an electrically evoked twitch declined in a similar
      way in DEX and placebo. Similarly, the EMG root mean square was similar with DEX
      and placebo treatment. CONCLUSION: Short-term dexamethasone administration
      increases high-intensity one-legged kicking time to exhaustion and 20-m shuttle
      run performance, although sprint ability and the initial loss of muscular force
      generating capacity are similar after DEX and placebo.

PMID- 24327178
TI  - Meaningful deadlines.

PMID- 24327179
TI  - Peer review farce.

PMID- 24327180
TI  - Driving quality.

PMID- 24327181
TI  - Using community service to promote awareness of health care-related resources,
      volunteerism, and teamwork in an incoming medical school class.
AB  - Community service has a documented correlation with improved medical school
      performance. To promote community service and awareness of community resources, a
      Community Service Day was integrated into orientation for incoming first-year
      students at Baylor College of Medicine. One hundred seventy-five first-year
      medical students and 31 second-year leaders volunteered at 11 community sites. We
      hoped this early introduction to community service would make students more aware
      of community resources and motivate them to continue volunteering throughout
      their medical training. Students were surveyed about their experiences. Seventy
      percent of responding students reported the service day helped them learn about
      the community's resources related to health care, and 92% reported it helped them
      get to know their classmates. We concluded that integrating a Community Service
      Day into medical student orientation is a successful way to expose students to
      community resources, while simultaneously encouraging camaraderie and teamwork
      among classmates.

PMID- 24327182
TI  - Syria: a healthcare system on the brink of collapse.

PMID- 24327184
TI  - International traineeships in AIDS prevention studies: 25 years of collaborative
      research.

PMID- 24327185
TI  - Between and within couple-level factors associated with gay male couples'
      investment in a sexual agreement.
AB  - Sexual agreements are common among gay male couples, and between one-third and
      two-thirds of gay men acquire HIV while in a same-sex relationship. Studies have
      assessed whether agreements could be used for HIV prevention yet additional
      research is needed. By using dyadic data collected from 361 U.S. gay male
      couples, the present cross-sectional study sought to assess whether certain
      between and within couple-level relationship characteristics predict a partner's
      value in, commitment to, and satisfaction with an agreement. On average, couples
      with higher levels of constructive communication and relationship satisfaction
      and commitment were associated with partners who had higher levels of investment
      in the agreement. Within the couple, differences in commitment and investment of
      the relationship were also found to be negatively associated with partners'
      investment toward an agreement. Implications are discussed for how sexual
      agreements may be used to develop new HIV prevention efforts for gay male
      couples. 

PMID- 24327186
TI  - The recognition of the personality disorders among young people.
AB  - BACKGROUND: Previous research suggests that mental health literacy regarding the
      personality disorders is low, with few disorders being recognised. AIMS: The
      current study aimed to examine the effect of a background in psychology as a
      predictor of knowledge of the personality disorders. METHODS: An opportunistic
      sample of 165 participants (mean age = 30.12 years, standard deviation (SD) =
      15.27 years) took part in the study. Participants were instructed to read 10
      personality disorder vignettes and other 'filler' items and rate each person in
      terms of how happy, successful at work and good at personal relationships they
      are, as well as whether they have a psychological problem. RESULTS: Results
      showed, as predicted, that those with a background in psychology were more
      accurate at labelling disorders. In addition, laypeople's mental health literacy
      was good for identifying the presence of personality disorders, but was
      considerably poorer when naming them. CONCLUSION: Recognising that people may
      have a disorder and having a 'correct' or recognised label are not the same
      thing.

PMID- 24327187
TI  - Religiosity, health and happiness: significant relations in adolescents from
      Qatar.
AB  - BACKGROUND: Several studies have revealed positive associations between
      religiosity, health and happiness. However, the vast majority of these studies
      were carried out on native English-speaking participants. AIMS: The objective of
      this study was to estimate the relations between religiosity, health and
      happiness among a sample (N = 372) of Qatari adolescents (M age = 15.2). METHOD:
      The students responded to five self-rating scales to assess religiosity, mental
      health, physical health, happiness and satisfaction with life. RESULTS: Boys
      obtained a higher mean score on mental health than did their female counterparts.
      All the correlations between the rating scales were significant and positive.
      Principal component analysis disclosed one component and labelled 'Religiosity,
      health and happiness' in both sexes. The multiple stepwise regression indicated
      that the predictors of religiosity were the self-ratings of satisfaction with
      life and happiness in boys, whereas the predictors among girls were satisfaction
      with life and physical health. CONCLUSIONS: On the basis of the responses of the
      present sample, it was concluded that those who consider themselves as religious
      were more happy, satisfied with their life and healthy.

PMID- 24327188
TI  - U-shaped sacral fracture with iliac crest apophyseal avulsion in a young child.
AB  - BACKGROUND: U-shaped sacral fractures or Jumper's fractures are rare injuries in
      adults and are even rarer in the pediatric population. These fractures share a
      common pathoanatomy where the pelvis as a unit together with the bilateral alar
      parts and the lower part of the sacrum, loses its skeletal and soft tissue
      connections to the remaining axial skeleton and hence the term spinopelvic
      dissociation. This report describes an unusual pattern of spinopelvic
      dissociation in a young child where the transverse process of the fifth lumbar
      vertebra was avulsed on one side (spinal side avulsion), whereas on the other
      side, complete iliac crest apophyseal avulsion took place (pelvic sided
      avulsion). To our knowledge, this combination of injuries was not reported
      before. The available literature describing pediatric U-shaped sacral fractures
      were also reviewed to help explain the pathoanatomic basis of this association.
      METHODS: An 8-year-old boy sustained a U-shaped sacral fracture with avulsion of
      the left iliac crest apophysis. A search in the English literature was performed
      for all reports of U-shaped sacral fractures in pediatric patients (<= 18 y of
      age), as well as the relevant literature, which describes the pathoanatomy,
      possible radiologic findings, and current classification systems and treatment
      options. RESULTS: Fixation using a 7.3 mm percutaneous iliosacral screw was
      performed. At the latest follow-up, the child had no pain, was fully bearing
      weight on lower extremities, and was neurologically intact. The literature review
      yielded 6 other pediatric patients with U-shaped sacral fractures in 4 articles.
      CONCLUSIONS: In young children with immature pelvis, the iliac apophysis may be
      avulsed instead of the transverse process of the fifth lumbar vertebra by forces
      transmitted through the iliolumbar ligament. The apophysis will therefore keep
      its attachment to the abdominal and trunk muscles, whereas the bony iliac wing
      and the pelvis would be dissociated from the axial skeleton. Otherwise, the
      pathoanatomy of these injuries is the same as described in adults. LEVEL OF
      EVIDENCE: Level IV.

PMID- 24327190
TI  - Efficient single-strand cleavage of DNA mediated by a MnIIIMnIV-based artificial
      nuclease.
AB  - A water-soluble Mn(IV) 1,4,7-triazacyclononane complex, [Mn(IV)2L2(MU
      O)2](ClO4)2.2H2O (1), was prepared to serve as a nuclease mimic (L = 1,4,7
      triazacyclononane-N-acetate). Complex 1 was readily synthesized from the highly
      water soluble ligand (L), with Mn(III) salt, [Mn3O(MeCO2)7].3H2O in basic
      condition, and characterized by X-ray, IR, electronic spectroscopy, cyclic
      voltammetry and magnetic susceptibility as well as ESI-MS. The bond valence sum
      (BVS) analysis and magnetic data suggest that 1 is a Mn(IV)-MU-O2-Mn(IV) species.
      The electrospray mass spectrum and electronic spectrum of 1 in aqueous solution
      indicates that dinuclear Mn complex [Mn(III)Mn(IV)L2(MU-O)2](+) (2) is the active
      species. A predominantly hydrolytic cleavage mechanism was confirmed through
      experiments performed in the presence of various radical scavengers, T4 ligase
      and under anaerobic conditions. The kinetic aspects of DNA cleavage under pseudo-
      or true-Michaelis-Menten conditions were also detailed, kinetic parameters (kcat,
      KM, Vmax) were calculated to be 6.27 h(-1), 7.35 * 10(-5) M, 4.6 * 10(-4) M h(
      1); 0.683 h(-1), 1.93 * 10(-5) M, 1.32 * 10(-5) M h(-1) for 2, respectively. 

PMID- 24327192
TI  - NO Fluorescence Quantification by Chitosan CdSe Quantum Dots Nanocomposites.
AB  - The quantification of nitric oxide (NO) based on the quenching of the
      fluorescence of a nanocomposites sensor constituted by cadmium/selenium quantum
      dots (CdSe) stabilized by chitosan (CS) and mercaptosuccinic acid (MSA) is
      assessed. The optimization of the response of the CS-CdSe-MSA nanocomposites to
      NO was done by multivariate response surface experimental design methodologies.
      The highest fluorescence quenching was obtained at pH 5.5 and at room
      temperature. The NO quantification capability of CS-CdSe-MSA was evaluated using
      standard solutions and a NO donor reagent. A large linear working range from 5 to
      200 MUM and a limit of detection of 1.86 MUM were obtained. Better quantification
      results were obtained using the NO donor reagent. Besides NO, the response of the
      fluorescence of CS-CdSe-MSA to the main reactive oxygen and nitrogen species and
      similar NO compounds was also assessed. 

PMID- 24327191
TI  - Identification and functional characterization of nonmammalian Toll-like receptor
      20.
AB  - Like other vertebrate Toll-like receptors (TLRs), the TLRs of teleost fish can be
      subdivided into six major families, each of which recognize a general class of
      molecular patterns. However, there also are a number of Tlrs with unknown
      function, the presence of which seems unique to the bony fish, among which is
      Tlr20. We identified full-length complementary DNA (cDNA) sequences for tlr20 of
      zebrafish and common carp, two closely related fish species. Zebrafish have six
      copies of tlr20, whereas carp express only a single copy. Both zebrafish Tlr20
      (at least Tlr20a-d) and carp Tlr20 have 26 leucine-rich repeats (LRRs). Three
      dimensional modeling indicates a best fit to the crystal structure of TLR8.
      Phylogenetic analyses place Tlr20 in the TLR11 family closest to Tlr11 and Tlr12,
      which sense ligands from protozoan parasites in the mouse. Conservation of genes
      on zebrafish chromosome 9, which carries tlr20, with genes on mouse chromosome
      14, which carries tlr11, indicates Tlr11 could be a possible ortholog of Tlr20.
      Confocal microscopy suggests a subcellular localization of Tlr20 at the
      endoplasmatic reticulum. Although in vitro reporter assays could not identify a
      ligand unique to Tlr20, in vivo infection experiments indicate a role for Tlr20
      in the immune response of carp to protozoan parasites (Trypanoplasma borreli).
      Carp tlr20 is mainly expressed in peripheral blood leukocytes (PBL) with B
      lymphocytes, in particular, expressing relatively high levels of Tlr20. In vitro
      stimulation of PBL with T. borreli induces an upregulation of tlr20, supportive
      of a role for Tlr20 in the immune response to protozoan parasites. 

PMID- 24327189
TI  - WHODAS 2.0 in prodromal Huntington disease: measures of functioning in
      neuropsychiatric disease.
AB  - Clinical trials to improve day-to-day function in Huntington disease (HD) require
      accurate outcome measures. The DSM-5 recommends the World Health Organization
      Disability Assessment Schedule (WHODAS) 2.0 for use in neuropsychiatric
      disorders. The DSM-5 also states proxy measures may be useful when cognitive
      function may be impaired. We tested WHODAS participant and companion ratings for
      differences in baseline and longitudinal function in three prodromal HD groups
      and a control group. Participants with prodromal HD were stratified by disease
      progression (low, medium, and high disease burden) based on their cytosine
      adenine-guanine (CAG)-age product (CAP) score. Participant (N=726) and companion
      (N=630) WHODAS scores were examined for group differences, and for participant
      versus companion differences using linear mixed effects regression and Akaike's
      information criterion to test model fit. We also compared WHODAS with the Total
      Functional Capacity (TFC) scale. At baseline, functioning on the WHODAS was rated
      worse by participants in the high group and companions compared with controls.
      For longitudinal changes, companions reported functional decline over time in the
      medium and high groups. In simultaneous analysis, participant and companion
      longitudinal trajectories showed divergence in the high group, suggesting reduced
      validity of self-report. The WHODAS showed greater longitudinal difference than
      the TFC in the medium group relative to controls, whereas the TFC showed greater
      longitudinal difference than WHODAS in the high group. Results suggest the WHODAS
      can identify baseline and longitudinal differences in prodromal HD and may be
      useful in HD clinical trials. Companions may provide more accurate data as the
      disease progresses. 

PMID- 24327194
TI  - [Correction of complex facial scars].
AB  - Correction of complex facial scars frequently requires individualized, multimodal
      strategies, which are composed of various therapeutic measures. This report
      provides information on techniques for correction of contractures, atrophic
      scars, scars within hair-bearing regions of the face and auricular keloids.
      Additionally, we present adjuvant procedures in a subject-related manner. 

PMID- 24327195
TI  - [Quality control following reconstructive middle ear surgery: from bench to
      bedside].
AB  - BACKGROUND: The ongoing improvement of imaging quality nowadays focuses
      increasingly more on immediate quality evaluation of surgical measures. METHODS:
      Rotational tomography (RT) has been experimentally proven to be an alternative
      imaging technique to computed tomography (CT) in terms of quality and
      postoperative localization of middle ear implants in temporal bones. Based on
      these results imaging parameters were determined in the form of a surgical check
      list in order to systematically check individual but important surgical
      reconstructive steps. RESULTS: The positive benefit of RT concerning immediate
      and significant postoperative quality control was confirmed by a patient study.
      The surgical check list was successfully implemented under clinical framework
      requirements. Among these standardized parameters the determined angulation of
      inserted middle ear implants was given outstanding significance due to the
      predictive value concerning functional outcome. CONCLUSION: The RT procedure has
      been proven to be a reliable imaging tool for postoperative quality control
      following reconstructive middle ear surgery.

PMID- 24327196
TI  - [The patulous eustachian tube-novel surgical approaches].
AB  - A patulous eustachian tube (tuba aperta) may lead to an enormous reduction in
      quality of life. A patulous eustachian tube can cause symptoms such as autophony,
      breath synchronous tinnitus, pressure sensation in the ear, and hearing loss. In
      combination with so-called "sniffing", it can trigger the development of
      cholesteatoma. Due to the diffuse symptoms the correct diagnosis of this disease
      can be challenging. A patulous eustachian tube can be best diagnosed through a
      well-structured examination including patient history, physical examination with
      thorough observation of movements of the tympanic membrane, and tympanometry with
      reflex decay. This publication reviews recent literature on the patulous
      eustachian tube. We focused on the evaluation of the different surgical
      strategies such as the patulous eustachian tube reconstruction, the Kobayashi
      plug or the injection of Vox(r) implants into the torus tubarius. 

PMID- 24327197
TI  - [Psycho-oncology for speech therapists: establishment and conception of the
      course PSYKOL].
AB  - OBJECTIVE: Head and neck cancer patients show a high psychiatric comorbidity, yet
      receive only little psychosocial support. Therefore, a specific psychosocial
      qualification for speech therapists working with head and neck cancer patients
      seems necessary. MATERIAL AND METHODS: A course was developed based on a process
      model. Questionnaires were completed by speech therapists (self-evaluation of
      working situation; n = 15) as well as therapists interested in further training
      (collection of issues in the work with head and neck patients who are under
      psychological pressure assessed as problematic by the therapists; n = 27), whose
      competence in communication was also evaluated. In addition, a literature
      research was conducted and a focus group was formed. RESULTS: High psychosocial
      demands within the therapists' work with tumor patients and difficulties in
      communication became obvious. Nearly all interviewees frequently used
      nonconducive communication patterns, yet implicit knowledge existed (usage of a
      favorable conversational style in multiple choice test: 68 %). The content and
      concept of the curriculum were discussed within the focus group and led to the
      final version of the training. CONCLUSION: A customised psycho-social training
      curriculum for speech therapists has been developed.

PMID- 24327198
TI  - [Medical examination: preparation for ENT specialisation : part 12].

PMID- 24327199
TI  - [Modern, minimally invasive surgery of the lacrimal duct system].
AB  - Epiphora (tearing) is the main symptom of a dysfunction of the lacrimal drainage.
      Tearing is a common problem and the cause can not easily be identified. Since
      development and miniaturisation of gastroduodenal endoscopes in the 1990s, it is
      possible to check the anatomical structure and the pathological changes of the
      lacrimal drainage system, which has a diameter of 1 mm. Mechanical stenosis is
      often caused by recurring chronic inflammation. Complete stenosis is usually only
      punctual and seldom over a long distance. Shortly after the development of
      microendoscopic diagnostic tools, therapeutic techniques using a laser for the
      dacryoplasty (LDP) or a microdrill for the dacryoplasty (MDP) were established.
      For the first time, these treatments enable preservation of the whole physiology
      of the lacrimal drainage system in spite of surgical intervention. 

PMID- 24327200
TI  - Magneto-transport characteristics of a 2D electron system driven to negative
      magneto-conductivity by microwave photoexcitation.
AB  - Negative diagonal magneto-conductivity/resistivity is a spectacular- and thought
      provoking-property of driven, far-from-equilibrium, low dimensional electronic
      systems. The physical response of this exotic electronic state is not yet fully
      understood since it is rarely encountered in experiment. The microwave-radiation
      induced zero-resistance state in the high mobility GaAs/AlGaAs 2D electron system
      is believed to be an example where negative magneto-conductivity/resistivity is
      responsible for the observed phenomena. Here, we examine the magneto-transport
      characteristics of this negative conductivity/resistivity state in the microwave
      photo-excited two-dimensional electron system (2DES) through a numerical solution
      of the associated boundary value problem. The results suggest, surprisingly, that
      a bare negative diagonal conductivity/resistivity state in the 2DES under photo
      excitation should yield a positive diagonal resistance, with a concomitant sign
      reversal in the Hall voltage. 

PMID- 24327201
TI  - Indicators of collapse in systems undergoing unsustainable growth.
AB  - Unsustainable growth is typical of systems that rely on a finite pool of non
      renewable resources that are tapped until they are depleted. The decrease in
      resource availability eventually leads these systems to a decline. Here we
      investigate the dynamics of systems that exhibit unsustainable growth and are
      prone to a collapse to an alternative ("degraded") state. For these systems the
      possible imminent occurrence of a collapse is difficult to avert because they
      keep growing as they approach the transition point. It is therefore important to
      identify some early warning signs that can be used to predict whether the system
      is approaching a critical and likely irreversible transition to an undesired and
      degraded state. This study evaluates whether existing theories of precursors of
      phase transitions based on the critical slowing down phenomenon are applicable as
      leading indicators of state shift in unsustainable growth dynamics. It is found
      that such indicators fail to serve as reliable early warning signs of the
      system's collapse. 

PMID- 24327202
TI  - Management of humeral head deficiencies and glenoid track.
AB  - When considering the management of shoulder anterior instability with glenoid
      bone loss >=25 % of the inferior glenoid diameter (inverted-pear glenoid), the
      consensus among recent authors is that glenoid bone grafting should be done.
      Although the engaging Hill-Sachs lesion has been recognized as a risk factor for
      recurrent anterior instability, there has been no generally accepted methodology
      for quantifying the Hill-Sachs lesion taking into account the geometric interplay
      of various sizes and various orientations of bipolar (humeral-sided plus glenoid
      sided) bone loss. Keeping the glenoid track concept in mind, if a Hill-Sachs
      lesion engages the anterior glenoid rim, with or without concomitant anterior
      glenoid bone loss, it is possible to manage this pathology, reducing the risk of
      recurrent shoulder instability after surgery. If the Hill-Sachs engages,
      "Remplissage" or "Latarjet" surgical procedures are indicated depending of
      glenoid bone loss. 

PMID- 24327203
TI  - The effect of metals on SDS-induced partially folded states of CopC.
AB  - In this work, the unfolding of CopC was used to elucidate details of the protein
      structure through different spectroscopic techniques. The interactions of CopC
      and its mutants with the anionic surfactant sodium dodecyl sulfate (SDS),
      guanidinium hydrochloride, and urea were monitored by fluorescence spectroscopy,
      far-UV circular dichroism spectroscopy, and fluorescence lifetime measurements.
      The interaction of SDS with CopC resulted in the formation of a partially folded
      intermediate. In this intermediate, the structure of the C-terminal is unfolded,
      whereas the N-terminal retains the native structure. Further, we have explored
      the effects of metals on the intermediate in aqueous surfactant. The results
      suggested that the Ag(+) ion has a large effect on the unfolding induced by SDS.
      In addition, the binding capacity of the different unfolding degree protein
      toward Cu(2+) indicated the high stability of the N-terminal. The protein-Cu(2+)
      unfolding induced by guanidinium hydrochloride and urea caused the binding of
      Cu(2+) to increase the stability of the N-terminal, which resulted in an
      intermediate in the unfolding process. The first transition corresponded to
      unfolding of the C-terminal, and the second transition was attributed to
      unfolding of the N-terminal. Furthermore, the anisotropy decay indicated that the
      motion of tryptophan occurred at a higher urea concentration, which suggested the
      high stability of the N-terminal. Steered molecular dynamics simulations also
      indicated that the structure of the N-terminal was rigid. 

PMID- 24327204
TI  - Kv7 potassium channel subunits and M currents in cultured hippocampal
      interneurons.
AB  - Potassium channels of the Kv7 family that mediate the non-inactivating M current
      regulate the excitability of many types of neurons in the central nervous system,
      including some in the hippocampus. We report here that individual interneurons
      from newborn rat hippocampi in long-term culture strongly express messenger RNA
      specific for Kv7.2 and Kv7.3 and, to a lesser extent, Kv7.5 channel subunits but
      not for the Kv7.4 subunit. An M-like current was electrophysiologically
      identified in two subpopulations of interneurons distinct in their spiking
      behaviour (regular or fast spiking). The M-channel enhancer retigabine reduced
      interneuronal excitability by constraining the number of action potentials
      generated during imposed depolarisations; this effect was inhibited by specific
      the M-channel blocking drugs. In paired synaptically connected interneuron-target
      cell recordings, anatomically localised applications of retigabine indicated that
      M channels were present in both the interneuron soma and its GABA-ergic
      inhibitory axon. We conclude that M-channel subunits and functional M channels
      are broadly expressed in hippocampal interneurons and their axons and are
      potentially capable of strongly regulating their firing properties. 

PMID- 24327205
TI  - 5,6-EET potently inhibits T-type calcium channels: implication in the regulation
      of the vascular tone.
AB  - T-type calcium channels (T-channels) are important actors in neuronal pacemaking,
      in heart rhythm, and in the control of the vascular tone. T-channels are
      regulated by several endogenous lipids including the primary eicosanoid
      arachidonic acid (AA), which display an important role in vasodilation via its
      metabolism leading to prostanoids, leukotrienes, and epoxyeicosatrienoic acids
      (EETs). However, the effects of these latter molecules on T-currents have not
      been investigated. Here, we describe the effects of the major cyclooxygenase,
      lipoxygenase, and cytochrome P450 epoxygenase products on the three human
      recombinant T-channels (Cav3.1, Cav3.2, and Cav3.3), as compared to those of AA.
      We identified the P450 epoxygenase product, 5,6-EET, as a potent physiological
      inhibitor of Cav3 currents. The effects of 5,6-EET were observed at sub
      micromolar concentrations (IC50 = 0.54 MUM), occurred in the minute range, and
      were reversible. The 5,6-EET inhibited the Cav3 currents at physiological resting
      membrane potentials mostly by inducing a large negative shift in their steady
      state inactivation properties. Using knockout mice for Cav3.1 and Cav3.2, we
      demonstrated that the vasodilation of preconstricted mesenteric arteries induced
      by 5,6-EET was specifically impaired in Cav3.2 knockout mice. Overall, our
      results indicate that inhibition of Cav3 currents by 5,6-EET is an important
      mechanism controlling the vascular tone. 

PMID- 24327206
TI  - Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in
      electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen
      species and NHE-1.
AB  - Emerging evidence supports a key role for endothelin-1 (ET-1) and the
      transactivation of the epidermal growth factor receptor (EGFR) in angiotensin II
      (Ang II) action. We aim to determine the potential role played by endogenous ET
      1, EGFR transactivation and redox-dependent sodium hydrogen exchanger-1 (NHE-1)
      activation in the hypertrophic response to Ang II of cardiac myocytes.
      Electrically paced adult cat cardiomyocytes were placed in culture and stimulated
      with 1 nmol l(-1) Ang II or 5 nmol l(-1) ET-1. Ang II increased ~45 % cell
      surface area (CSA) and ~37 % [(3)H]-phenylalanine incorporation, effects that
      were blocked not only by losartan (Los) but also by BQ123 (AT1 and ETA receptor
      antagonists, respectively). Moreover, Ang II significantly increased ET-1
      messenger RNA (mRNA) expression. ET-1 similarly increased myocyte CSA and protein
      synthesis, actions prevented by the reactive oxygen species scavenger MPG or the
      NHE-1 inhibitor cariporide (carip). ET-1 increased the phosphorylation of the
      redox-sensitive ERK1/2-p90(RSK) kinases, main activators of the NHE-1. This
      effect was prevented by MPG and the antagonist of EGFR, AG1478. Ang II, ET-1 and
      EGF increased myocardial superoxide production (187 +/- 9 %, 149 +/- 8 % and
      163.7 +/- 6 % of control, respectively) and AG1478 inhibited these effects.
      Interestingly, Los inhibited only Ang II whilst BQ123 cancelled both Ang II and
      ET-1 actions, supporting the sequential and unidirectional activation of AT1, ETA
      and EGFR. Based on the present evidence, we propose that endogenous ET-1 mediates
      the hypertrophic response to Ang II by a mechanism that involves EGFR
      transactivation and redox-dependent activation of the ERK1/2-p90(RSK) and NHE-1
      in adult cardiomyocytes. 

PMID- 24327207
TI  - Modeling of Friedreich ataxia-related iron overloading cardiomyopathy using
      patient-specific-induced pluripotent stem cells.
AB  - Friedreich ataxia (FRDA), a recessive neurodegenerative disorder commonly
      associated with hypertrophic cardiomyopathy, is due to GAA repeat expansions
      within the first intron of the frataxin (FXN) gene encoding the mitochondrial
      protein involved in iron-sulfur cluster biosynthesis. The triplet codon repeats
      lead to heterochromatin-mediated gene silencing and loss of frataxin.
      Nevertheless, inadequacy of existing FRDA-cardiac cellular models limited
      cardiomyopathy studies. We tested the hypothesis that iron homeostasis
      deregulation accelerates reduction in energy synthesis dynamics which contributes
      to impaired cardiac calcium homeostasis and contractile force. Silencing of FXN
      expressions occurred both in somatic FRDA-skin fibroblasts and two of the induced
      pluripotent stem cells (iPSC) clones; a sign of stress condition was shown in
      FRDA-iPSC cardiomyocytes with disorganized mitochondrial network and
      mitochondrial DNA (mtDNA) depletion; hypertrophic cardiac stress responses were
      observed by an increase in alpha-actinin-positive cell sizes revealed by FACS
      analysis as well as elevation in brain natriuretic peptide (BNP) gene expression;
      the intracellular iron accumulated in FRDA cardiomyocytes might be due to
      attenuated negative feedback response of transferring receptor (TSFR) expression
      and positive feedback response of ferritin (FTH1); energy synthesis dynamics, in
      terms of ATP production rate, was impaired in FRDA-iPSC cardiomyocytes, which
      were prone to iron overload condition. Energetic insufficiency determined slower
      Ca(2+) transients by retarding calcium reuptake to sarcoplasmic reticulum (SR)
      and impaired the positive inotropic and chronotropic responses to adrenergic
      stimulation. Our data showed for the first time that FRDA-iPSCs cardiac
      derivatives represent promising models to study cardiac stress response due to
      impaired iron homeostasis condition and mitochondrial damages. The cardiomyopathy
      phenotype was accelerated in an iron-overloaded condition early in calcium
      homeostasis aspect. 

PMID- 24327208
TI  - MYBPC3's alternate ending: consequences and therapeutic implications of a highly
      prevalent 25 bp deletion mutation.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common form of inherited cardiac
      disease and the leading cause of sudden cardiac death in young people. HCM is
      caused by mutations in genes encoding contractile proteins. Cardiac myosin
      binding protein-C (cMyBP-C) is a thick filament contractile protein that
      regulates sarcomere organization and cardiac contractility. About 200 different
      mutations in the cMyBP-C gene (MYBPC3) have thus far been reported as causing
      HCM. Among them, a 25 base pair deletion in the branch point of intron 32 of
      MYBPC3 is widespread, particularly affecting people of South Asian descent, with
      4% of this population carrying the mutation. This polymorphic mutation results in
      skipping of exon 33 and a reading frame shift, which, in turn, replaces the last
      65 amino acids of the C-terminal C10 domain of cMyBP-C with a novel sequence of
      58 residues (cMyBP-C(C10mut)). Carriers of the 25 base pair deletion mutation are
      at increased risk of developing cardiomyopathy and heart failure. Because of the
      high prevalence of this mutation in certain populations, genetic screening of at
      risk groups might be beneficial. Scientifically, the functional consequences of C
      terminal mutations and the precise mechanisms leading to HCM should be defined
      using induced pluripotent stem cells and engineered heart tissue in vitro or
      mouse models in vivo. Most importantly, therapeutic strategies that include
      pharmacology, gene repair, and gene therapy should be developed to prevent the
      adverse clinical effects of cMyBP-C(C10mut). This review article aims to examine
      the effects of cMyBP-C(C10mut) on cardiac function, emphasizing the need for the
      development of genetic testing and expanded therapeutic strategies. 

PMID- 24327209
TI  - Stem cell gene SALL4 in aggressive hepatocellular carcinoma: a cancer stem cell
      specific target?

PMID- 24327210
TI  - Understanding change in recycling and littering behavior across a school social
      network.
AB  - Understanding how communities change requires examining how individuals' beliefs
      and behaviors are shaped by those around them. This paper investigates behavior
      change across a large social network following a recycling intervention in a New
      Zealand high school community. We used a mixed methods design, combining focus
      group data with social network analysis from two waves of a questionnaire that
      measured friendship networks; recycling and littering behaviors; perceived
      behavioral norms; and teacher, friend, and parent encouragement for these
      behaviors. Recycling behavior increased significantly over the course of our
      study. Supporting the importance of social networks in this context, both
      littering and recycling behavior showed clear social clustering. Further, the
      degree of change in an individuals' littering and recycling behavior across time
      was predicted by friends' prior behavior. Focus group data provided insight into
      students' perceptions of social interactions and how these contributed to
      littering and recycling behavior. 

PMID- 24327211
TI  - Biotechnological transformation of hydrocortisone to 16alpha-hydroxy
      hydrocortisone by Streptomyces roseochromogenes.
AB  - Streptomyces roseochromogenes is able to hydroxylate steroid compounds in
      different positions of their cycloalkane rings thanks to a cytochrome P-450 multi
      enzyme complex. In this paper, the hydroxylation of the hydrocortisone in the
      16alpha position, performed by bacterial whole cells, was investigated in both
      shake flask and fermentation conditions; the best settings for both cellular
      growth and transformation reaction were studied by investigating the optimal
      medium composition, the kinetic of conversion, the most suitable substrate
      concentration and the preferred addition timing. Using newly formulated malt
      extract- and yeast extract-based media, a 16alpha-hydrohydrocortisone
      concentration of 0.2 +/- 0.01 g L(-1) was reached in shake flasks. Batch
      experiments in a 2-L fermentor established the reproducibility and robustness of
      the biotransformation, while a pulsed batch fermentation strategy allowed the
      production to increase up to 0.508 +/- 0.01 g L(-1). By-product formation was
      investigated, and two new derivates of the hydrocortisone obtained during the
      bacterial transformation reaction and unknown so far, a C-20 hydroxy derivate and
      a C-21 N-acetamide one, were determined by NMR analyses.

PMID- 24327212
TI  - A new synthetic ligand that activates QscR and blocks antibiotic-tolerant biofilm
      formation in Pseudomonas aeruginosa.
AB  - Quorum sensing (QS) has been recognized to play an important role in many
      pathogenic bacteria and has become a novel target for the treatment of infectious
      disease. Pseudomonas aeruginosa is highly resistant to antibiotic treatment,
      largely due to its ability to form biofilms, and QS was found to be essential for
      the creation of mature, differentiated biofilms in this organism. A novel QS
      inhibitor, C2 (N-decanoyl-L-homoserine benzyl ester), can attenuate not only
      total protease and elastase activity, but also swarming motility and biofilm
      formation in the P. aeruginosa strain PAO1. We demonstrated that C2 showed a
      significant inhibitory effect on biofilm formation in a dose-dependent manner.
      Data from cDNA microarray showed that expression of 382 genes (~6.4 %) was
      significantly different with C2 treatment, including downregulation of 215 genes
      (~3.6 %) and upregulation of 167 genes (~2.8 %). Real-time reverse transcription
      polymerase chain reaction (RT-PCR) showed that the gene qscR, which encodes the
      LuxR-type receptor QscR (quorum sensing control repressor), was significantly
      upregulated by 375.4 % during C2 treatment. The mechanism by which C2 inhibits
      biofilm formation may be through repression of Las and Rhl systems by QscR. C2
      was shown to reduce biofilm formation; in combination with antibiotics, it
      abolishes biofilm formation completely. This result may pave the way for new
      treatments for biofilm-related infections and may be exploited for the general
      prevention of biofilm formation.

PMID- 24327213
TI  - Proteins improving recombinant antibody production in mammalian cells.
AB  - Mammalian cells have been successfully used for the industrial manufacture of
      antibodies due to their ability to synthesize antibodies correctly. Nascent
      polypeptides must be subjected to protein folding and assembly in the ER and the
      Golgi to be secreted as mature proteins. If these reactions do not proceed
      appropriately, unfolded or misfolded proteins are degraded by the ER-associated
      degradation (ERAD) pathway. The accumulation of unfolded proteins or
      intracellular antibody crystals accompanied by this failure triggers the unfolded
      protein response (UPR), which can considerably attenuate the levels of
      translation, folding, assembly, and secretion, resulting in reduction of antibody
      productivity. Accumulating studies by omics-based analysis of recombinant
      mammalian cells suggest that not only protein secretion processes including
      protein folding and assembly but also translation are likely to be the rate
      limiting factors for increasing antibody production. Here, this review describes
      the mechanism of antibody folding and assembly and recent advantages which could
      improve recombinant antibody production in mammalian cells by utilizing proteins
      such as ER chaperones or UPR-related proteins. 

PMID- 24327214
TI  - Pyloroduodenal duplication cysts: treatment of eleven cases.

PMID- 24327215
TI  - Endoloop as the first line tool for appendiceal stump closure in children with
      appendicitis.
AB  - PURPOSE: The objective of this study is to compare outcomes for pediatric
      patients undergoing laparoscopic appendectomy (LA) performed either (1) using an
      endostapler (ES) to divide the appendix and mesoappendix or (2) using endoloops
      (ELs) to close the appendiceal stump and electrocautery to divide the
      mesoappendix. METHODS: We conducted a retrospective chart review of all patients
      who underwent LA for suspected appendicitis 4 years at a free standing children's
      hospital. The use of EL and ES was compared separately in patients with
      perforated and nonperforated appendicitis. We compared patient characteristics
      and outcomes. RESULTS: There were no significant differences in rate of
      postoperative abscess, rate of subsequent small bowel obstruction requiring
      operation or rate of intraperitoneal hematoma between the ES and EL groups for
      both nonperforated and perforated appendectomy cases. Superficial wound infection
      was more common in the nonperforated EL group (17/309, 5.5%) than in the
      nonperforated ES group (2/235, 0.9%; p = 0.007). Operative time for the EL
      technique (52.2 +/- 15.8 minutes; p = 0.047) was shorter than for the ES
      technique (58 +/- 23.2 minutes) for patients with perforated appendicitis.
      CONCLUSION: EL stump closure and mesoappendix cauterization during LA is safe and
      effective in children with appendicitis, including perforated appendicitis.

PMID- 24327216
TI  - Ganglioneuroma: to operate or not to operate.
AB  - INTRODUCTION: Ganglioneuroma (GN) is a benign, differentiated variety of
      neurogenic tumor. It is often asymptomatic and may be diagnosed by serendipity.
      Surgical removal is the treatment of choice. However, it has been suggested that
      postoperative complications and sequelae might outweigh the benefits of this
      approach. The purpose of the present study was to examine these issues in a large
      experience of neural tumors. METHODS: Patients treated between 1992 and 2012 were
      retrospectively reviewed. Modern imaging, measurement of catecholamine metabolite
      excretion and metaiodobenzylguanidine were used for workup. Surgical treatment
      aimed at complete resection. Complications and sequelae were recorded. Literature
      was searched for regrowth or malignant transformation of GN. RESULTS: Of 227
      patients with neural tumors, 24 were GN patients (12 abdominal, 11 thoracic and 1
      cervical with 8 dumbbell extensions). Six children were symptomatic (three with
      abdominal pain and mass, one with stridor or dysphonia, and one each with
      anisocoria and opsomyoclonus). However, 18 (75%) were asymptomatic and the
      diagnosis was incidental. Several tumors were large and involved more than one
      body space. There were no neurologic symptoms in eight cases with dumbbell
      extension. Complete resection was achieved in 20 children (83%) whereas gross
      residual was left in four. Postoperative complications were: Horner syndrome (3
      patients), mild scoliosis (1 patient), adhesive bowel obstruction (1 patient) and
      acute urinary retention (1 patient). There was no evidence of either regrowth or
      malignant behavior in residual masses left in place after follow-up of 84 (1-194)
      months. CONCLUSIONS: There were a limited number of general minor complications
      in this series that did not include cases of regrowth or malignant
      transformation. However, these unfavorable events were occasionally reported in
      the literature. Since diagnosis of GN cannot be ascertained before removal of the
      mass, this should remain the aim of the treatment, although limiting the chances
      of complications to a minimum even if incomplete resection is the price to pay.
      Nonoperative attitudes should not be recommended in all cases, but they are
      certainly justified in some.

PMID- 24327217
TI  - Retrievable Z-stents for the treatment of refractory corrosive esophageal
      strictures in children.
AB  - INTRODUCTION: The use of retrievable esophageal stents represents a new method to
      avoid multiple dilations for stenosis recurrence. The aim of this study was to
      evaluate the efficacy of treatment with a retrievable covered Z-stent for
      corrosive esophageal stenosis in children. MATERIALS AND METHODS: A total of 15
      children were enrolled in this study. All patients had undergone balloon catheter
      dilatation (BCD) but without significant symptomatic improvement. A retrievable Z
      stent was placed, and the dysphagia score was evaluated. After stent removal,
      healing was considered to have occurred if the score was 0 to 1 for at least 12
      continuous months. RESULTS: Stents were placed in all children without
      complications and were later removed successfully. Stents remained in situ for 4
      to 8 weeks (mean, 7.4 weeks). Dysphagia scores decreased from 3 to 4 to 0 to 1 in
      all patients while the stent was in place. During the 12-month follow-up period,
      seven patients remained free from dysphagia, but eight children had recurrent
      stenosis and required a subsequent BCD to alleviate symptoms from the stricture.
      Six of them required placement of a second stent. CONCLUSIONS: The use of a
      retrievable Z-stent is an effective method and may become the treatment of choice
      for corrosive esophageal stenosis in children.

PMID- 24327218
TI  - Treatment of thoracic trauma in children: literature review, Red Cross War
      Memorial Children's Hospital data analysis, and guidelines for management.
AB  - INTRODUCTION: Thoracic injuries continue to be a leading cause of childhood
      trauma, despite the government's efforts to curb the scourge of this problem. Our
      review focuses on the incidence, etiology, and management of thoracic trauma in
      the pediatric population with reference to the recent experience at our
      institution in a developing country. METHODS: For the literature review, the
      National Library of Medicine's PubMed database was searched for the following
      terms: "pediatric," "chest trauma," "hemothorax," "hemopneumothorax,"
      "pneumothorax," "diaphragmatic," "esophageal," and "mediastinal injury." For the
      hospital data analysis, data of all 378 pediatric patients treated with thoracic
      injuries under the age of 13 years from 2008 to 2012 (a 5-year period), at the
      Red Cross War Memorial Children's Hospital, were retrospectively analyzed.
      RESULTS: The male to female ratio was 2.1:1 (255 males and 123 females). The mean
      age was 6.9 +/- 2.3 years. Blunt chest trauma was responsible for chest injuries
      in 90.5%, while penetrating trauma caused 9.5% of the injuries. Road traffic
      crashes were the mean cause (48.9%) with pedestrian injuries in 72.4% and
      passenger injuries in 27.6%, respectively. Sports injuries were the cause in 4%
      and falls from a height in 22%. Most injuries occurred at home: inside one's own
      home (5%), outside one's own home (52%); inside someone else's home (44%);
      outside someone else's home (2%). Public space injuries occurred at schools or
      creches in 77%, pavement or roads in 6%, and were not specified in 17%. Overall
      74% presented with injuries of the thoracic cage; rib fractures occurred in 13%,
      chest wall contusions in 40%, and abrasions in 31%. Respiratory system injuries
      occurred in 22%; hemothoraces in 23%, pneumothoraces in 45%, and
      hemopneumothoraces in 29%. Cardiovascular injuries occurred in 16% of cases with
      vascular injuries in five patients (two firearms injuries and three motor vehicle
      crashes). Management was nonoperative in 79.4%, tube thoracotomy in 17.2%, and
      open surgery in 3.4%. The mortality rate was 1.3%, all contributed by firearm
      related injuries and polytrauma. CONCLUSION: Thoracic trauma has remained a
      significant cause of morbidity and mortality in the pediatric population.
      Concerted effort from governments, civil societies, and the medical profession
      are needed to address this challenge.

PMID- 24327219
TI  - Developments in the treatment of pediatric long bone shaft fractures.
AB  - Shaft fractures of the long bones are among the most common pediatric injuries.
      They are characterized by a limited potential for spontaneous correction because
      of the fractures--distance to the physis. Although conservative treatment has
      been practiced for many years with satisfying results, several aspects have led
      to an increase in the numbers of surgical procedures including changes of living,
      sports habits, economics, and patients-request to treatment. We reviewed the
      literature to describe developments of treatment concepts of pediatric shaft
      fractures. In shaft fractures of the upper extremities, increasing rates of
      surgical procedures have been reported preventing functional deficits of forearm
      prosupination and cosmetic deformities of the humerus. In fractures of the lower
      extremities maximizing stability shifted into the focus of interest to achieve
      early mobilization and to compensate heavier body weights of children and
      adolescents. Consecutively, the current gold standard of pediatric shaft fracture
      treatment--ESIN (elastic stable intramedullary nailing)--has been modified
      repeatedly using end caps, prebended nails, and optimized surgical techniques. In
      addition, new methods such as rigid locking nails and plates have been included
      in the treatment approaches for femur and tibia shaft fractures. All these
      methods of pediatric fracture care carry inherent advantages that require
      consideration for each clinical situation. On the other side, this has enlarged
      the spectrum of potential complications, which needs continuous evaluation to
      further improve treatment results.

PMID- 24327220
TI  - Selective angioembolization in blunt solid organ injury in children and
      adolescents: review of recent literature and own experiences.
AB  - Nonoperative management (NOM) is considered the standard therapy for clinically
      stable children with blunt solid organ injuries (SOI) grade I to IV. The
      capability of angioembolization (AE) to decrease the NOM failure rate in adults
      with blunt SOI has been demonstrated. The inclusion of AE in the pediatric SOI
      management is rarely reported. The aim of this review is to evaluate the recent
      literature surrounding trauma-related AE in children focusing on criteria for
      patient selection for AE and on the success rates including the greater
      experience in adults and on our own little series with splenic and renal injuries
      at a Level 1 Trauma Center. The technique will be described in detail. Although
      already added to some institutional treatment protocols patient selection for AE
      is still without full consent. High-grade injury, active bleeding with contrast
      blush on computed tomography, threatening, or ongoing hemodynamic instability and
      pseudoaneurysm represent the most common criteria to admit AE. Patients'
      characteristics are often similar to those of NOM failure groups in trauma
      managements protocols without AE. The impact of this interventional approach is
      situated between the possibility for NOM in the obvious stable child and the need
      for open surgery in the obvious unstable patient with grade IV to grade V SOI.
      There is evidence that AE is capable to decrease the failure rate and
      complications in the NOM. Although available data are based on cohort studies
      rather than prospective randomized-controlled trials, we conclude, AE represents
      a safe and effective therapy and should be part of the interdisciplinary trauma
      management protocol for SOI in children and adolescents.

PMID- 24327221
TI  - Computed tomographic scan in head trauma: what is the rational in children?
AB  - Traumatic brain injury (TBI) is the consequence of external forces that
      traumatically injure the brain. Closed head injury is common in children and is
      estimated to result in 650,000 to 1 million emergency department visits annually
      with approximately 7,400 deaths in the United States. Mild TBI is the most common
      form of closed head injury and constitutes 80 to 90% of all the TBI. Cranial
      computed tomography (cCT) is performed in usually more than 50% of the patients,
      thus, resulting in an extreme overuse with the inherent risk for inducing
      malignancies. The purpose of this article is to review current approaches,
      recommendations, and guidelines on pediatric head trauma with special emphasis on
      cCT. Therefore, after an overview on classification and TBI scores, diagnostic
      imaging, and management rules for clinical important TBI, as well as own
      experience including remarks on cCT technique will be discussed. 

PMID- 24327222
TI  - Anterior cruciate ligament injuries in children and adolescents: a review of the
      recent literature.
AB  - In contrast to the treatment of avulsion lesions of the anterior cruciate
      ligament (ACL) the management of intrasubstance ACL tears in the skeletally
      immature patient remains controversial. Prospective studies could show that
      conservative treatment results in severe instability with concomitant
      intraarticular damage and poor function of the knee. Reconstruction of a torn ACL
      always carries the risk of damaging the open growth plates; with consecutively
      affecting the longitudinal or axial growth of the lower extremity either on the
      femoral or the tibial side. Thus, several surgical procedures are available to
      prevent adverse events mentioned above. The purpose of this study is to review
      the recent literature regarding the treatment algorithm for ACL injuries in
      skeletally immature patients. This review will (1) investigate the indications
      for ACL surgery in children; (2) determine if a surgical procedure is clinically
      superior in skeletally immature patients; and (3) correlate the adverse events
      with the surgical technique.

PMID- 24327223
TI  - Surgical closure of persistent arterial duct with minimal invasive anterior
      thoracotomy: an alternative technique.
AB  - Surgical approach for persistent ductus arteriosus ligation is typically a left
      lateral thoracotomy opening the pleural-space with left lung retraction. We
      describe an alternative approach, with a minimally invasive anterior parasternal
      incision. This is particularly adapted to preterm infants weighing less than 1.5
      kg. This approach ensures a good exposure of vessels. We believe that it is safe,
      reliable and reproducible. The learning curve should not be an issue for surgeons
      used to manage low weight patients.

PMID- 24327224
TI  - Laparoscopic button cholecystostomy for progressive familial intrahepatic
      cholestasis in two children.
AB  - BACKGROUND: Untreated, progressive familial intrahepatic cholestasis (PFIC)
      results in fibrosis, cirrhosis, and liver failure. It has been shown that partial
      external biliary diversion (PEBD) may prevent from liver transplantation in
      patients without cirrhosis. The aim of this study is to present a new
      laparoscopic technique using a button instead of a bowel conduit for PEBD.
      PATIENTS AND METHODS: Two boys with PFIC (patient 1, 17 months; patient 2, 12
      years) underwent laparoscopic button cholecystostomy using a 3-trocar technique
      by insertion of a 14 French MIC KEY button (Kimberly-Clark Worldwide, Inc,
      Draper, Utah, United States) at the gallbladder fundus secured with two
      absorbable purse-string sutures. Beside the suitability of the procedure, end
      points included course of serum bile acids, total bilirubin, liver enzymes, and
      pruritus at a follow-up of 6 months. RESULTS: No complications related to the
      operation occurred. Relieve of pruritus was achieved in both the children, due to
      adequate bile drainage during a follow-up period of 6 months. In patient 2, a 10
      mm gallstone was removed simultaneously. In patient 1, serum bile acids decreased
      from 12.3 to 6.6 umol/L and in patient 2, serum bile acids decreased from 106.3
      to 2.9 umol/L. Total bilirubin, aspartate amino transferase, alanine amino
      transferase, and gamma-glutamyltransferase are kept in normal ranges during
      follow-up. Patient's and parent's acceptance with the button was excellent.
      CONCLUSION: Laparoscopic button cholecystostomy is a simple, safe, and sufficient
      technique for PEBD in patients with PFIC. It achieves an adequate bile flow with
      consecutive relief of pruritus and avoids an enteric anastomosis.

PMID- 24327226
TI  - A magnetic ionic liquid based on tetrachloroferrate exhibits three-dimensional
      magnetic ordering: a combined experimental and theoretical study of the magnetic
      interaction mechanism.
AB  - A new magnetic ionic liquid (MIL) with 3D antiferromagnetic ordering has been
      synthetized and characterized. The information obtained from magnetic
      characterization was supplemented by analysis of DFT calculations and the magneto
      structural correlations. The result gives no evidence for direct iron-iron
      interactions, corroborating that the 3D magnetic ordering in MILs takes place via
      super-exchange coupling containing two diamagnetic atoms intermediaries. 

PMID- 24327227
TI  - Phenanthroline ligands are biologically more active than their corresponding
      ruthenium(II) arene complexes.
AB  - New cationic, half-sandwich Ru(II) arene compounds of general formula [(eta(6)
      arene)RuCl(kappa(2)-N,N-L)]X (where L are functionalized phenanthrolines such as
      1,10-phenanthroline-5-amine (aphen); 5,6-epoxy-5,6-dihydro-[1,10]phenanthroline
      (ephen); or 4,7-dihydroxy-1,10-phenanthroline (dhphen)) have been prepared to
      study their anticancer potential. All the isolated complexes have been fully
      characterized by spectroscopic and analytical techniques. The structure of endo
      [(eta(6)-p-cymene)RuCl(kappa(2)-N,N-ephen)]BF4, [2a](BF4), has been determined by
      X-ray crystallography. The in vitro cytotoxicity of the aphen and ephen
      phenanthrolines and their Ru derivatives [(eta(6)-p-cymene)RuCl(kappa(2)-N,N
      L)]Cl ([1a]Cl and [2a]Cl, respectively) assessed in tumour cell lines has shown
      that the free ligands are more active than the organometallic products, with
      aphen being the most potent specimen. Furthermore, the binding interaction of
      both [1a]Cl and aphen with calf thymus DNA (CT-DNA) has been investigated using a
      variety of thermodynamic and kinetic techniques. The aphen free ligand
      intercalates into DNA at low ligand content, whereas [1a]Cl forms with DNA a
      bifunctional partially intercalated-covalent complex, in which the intercalation
      constant is nearly three orders of magnitude lower than that of aphen. This
      finding demonstrates that the covalent binding noticeably weakens the
      intercalation, a feature presumably related to the higher cytotoxic activity of
      aphen relative to that of [1a]Cl.

PMID- 24327228
TI  - Adducts of nitrogenous ligands with rhodium(II) tetracarboxylates and
      tetraformamidinate: NMR spectroscopy and density functional theory calculations.
AB  - Complexation of tetrakis(MU2-N,N'-diphenylformamidinato-N,N')-di-rhodium(II) with
      ligands containing nitrile, isonitrile, amine, hydroxyl, sulfhydryl, isocyanate,
      and isothiocyanate functional groups has been studied in liquid and solid phases
      using (1)H, (13)C and (15)N NMR, (13)C and (15)N cross polarisation-magic angle
      spinning NMR, and absorption spectroscopy in the visible range. The complexation
      was monitored using various NMR physicochemical parameters, such as chemical
      shifts, longitudinal relaxation times T1 , and NOE enhancements. Rhodium(II)
      tetraformamidinate selectively bonded only unbranched amine (propan-1-amine),
      pentanenitrile, and (1-isocyanoethyl)benzene. No complexation occurred in the
      case of ligands having hydroxyl, sulfhydryl, isocyanate, and isothiocyanate
      functional groups, and more expanded amine molecules such as butan-2-amine and 1
      azabicyclo[2.2.2]octane. Such features were opposite to those observed in
      rhodium(II) tetracarboxylates, forming adducts with all kind of ligands. Special
      attention was focused on the analysis of Deltadelta parameters, defined as a
      chemical shift difference between signal in adduct and corresponding signal in
      free ligand. In the case of (1)H NMR, Deltadelta values were either negative in
      adducts of rhodium(II) tetraformamidinate or positive in adducts of rhodium(II)
      tetracarboxylates. Experimental findings were supported by density functional
      theory molecular modelling and gauge independent atomic orbitals chemical shift
      calculations. The calculation of chemical shifts combined with scaling procedure
      allowed to reproduce qualitatively Deltadelta parameters.

PMID- 24327229
TI  - [Early surgery for menisco-ligamental injuries in elite athletes].
AB  - For elite athletes with anterior cruciate ligament (ACL) rupture, surgical
      management in the acute phase has become widespread practice. After performing a
      selective review of the literature using PubMed, these results were compared with
      our own experience. Surgery including concomitant injuries should be performed
      within the first 48 h. The principal advantage for athletes is the possibility of
      an earlier return to training and competition. The acute treatment of concomitant
      injuries may also improve outcome. Treatment in the acute phase, however, may be
      more demanding for the surgeon than surgery at a later point in time. 

PMID- 24327230
TI  - [Typical injuries in snowboarding. Possible prevention strategies].
AB  - Due to the specific position on a snowboard, crashes often result in snowboard
      specific injuries. As snowboarding nowadays represents a mass sport, treatment of
      injured snowboarders is becoming common clinical practice. Optimal treatment
      makes knowledge about snowboard-specific injuries and their underlying mechanisms
      mandatory. The upper extremities are most frequently affected, with the most
      frequent injury being the distal radius fracture. Because especially beginners
      are more often injured, prevention strategies seem to be promising. It was
      demonstrated that wrist-protection guards are able to decrease the risk of
      suffering a distal radius fracture. Moreover, use of a helmet was also shown to
      be protective. Against this background, wearing protective gear such as wrist
      guards and helmets is strongly recommended to decrease injury severity and
      frequency. 

PMID- 24327231
TI  - [Bony injuries of the shoulder girdle in snowboarding].
AB  - BACKGROUND: The fracture of the clavicle is the second most common fracture in
      snowboarding after the distal radius fracture. Nonsurgical treatment is
      frequently the treatment of first choice. For displaced fractures, surgical
      treatment is recommended. METHODS: In general, internal fixation can be performed
      with a plate osteosynthesis or an intramedullary nail. Clinical studies were able
      to show similar and even slightly better functional results of the intramedullary
      nail in comparison to plate osteosynthesis. Because of less surgical trauma and
      better cosmetic results, intramedullary systems are increasingly preferred.
      RESULTS: Lateral clavicular fractures are more complex regarding surgical
      treatment due to their potential for concomitant ligamentous injuries. The hooked
      plate shows good clinical results with the advantage of addressing the fracture
      as well as the ligament injury in one step. The limitation of mobility during the
      first few postoperative weeks is the technique's main disadvantage. CONCLUSIONS:
      Ligament reconstruction with suture pulley systems as a stand-alone treatment or
      in combination with a locking plate osteosythesis are increasingly used due to
      their excellent clinical results with early postoperative mobilization.

PMID- 24327232
TI  - [Emergency radiographs in injured children and adolescents].
AB  - BACKGROUND: Adequate interpretation of radiographs of injured children and
      adolescents is key for appropriate treatment. For the purposes of structuring in
      hospital education and training, conventional radiographs obtained in the
      emergency department (ED) should be analyzed. MATERIAL AND METHODS: A total of
      10,232 radiographs of children and adolescents (0-17 years old) were analyzed
      retrospectively. Data was analyzed according to sex, age, time, radiograph, and
      type of insurance. RESULTS: The male to female ratio was 3:2. In all, 76% of all
      radiographs were processed during on-call duty hours. Radiographs of the ankle
      were ordered most at a rate of 11%. Radiographs of the skull, wrist, finger, and
      ankle stood out from the sum of all radiographs and together accounted for 40%.
      CONCLUSION: Radiographs of injured children are analyzed predominantly during on
      call duty hours. Frequently mandated radiographs should be diagnosed accurately
      and standard injuries should be well known. Particular attention should be
      directed to the typical injury patterns of the ankle joint.

PMID- 24327233
TI  - Rating the effectiveness of local tobacco policies for reducing youth smoking.
AB  - Important questions remain regarding the effectiveness of local tobacco policies
      for preventing and reducing youth tobacco use and the relative importance of
      these policies. The aims of this paper are to: (1) compare policy effectiveness
      ratings provided by researchers and tobacco prevention specialists for individual
      local tobacco policies, and (2) develop and describe a systematic approach to
      score communities for locally-implemented tobacco policies. We reviewed municipal
      codes of 50 California communities to identify local tobacco regulations in five
      sub-domains. We then developed an instrument to rate the effectiveness of these
      policies and administered it to an expert panel of 40 tobacco researchers and
      specialists. We compared mean policy effectiveness ratings obtained from
      researchers and prevention specialists and used it to score the 50 communities.
      High inter-rater reliabilities obtained for each sub-domain indicated substantial
      agreement among the raters about relative policy effectiveness. Results showed
      that, although researchers and prevention specialists differed on the mean levels
      of policy ratings, their relative rank ordering of the effectiveness of policy
      sub-domains were very similar. While both researchers and prevention specialists
      viewed local outdoor clean air policies as least effective in preventing and
      reducing youth cigarette smoking, they rated tobacco sales policies and
      advertising and promotion as more effective than the other policies. Moreover, we
      found high correlations between community scores generated from researchers' and
      prevention specialists' ratings. This approach can be used to inform research on
      local policies and prevention efforts and help bridge the gap between research
      and practice. 

PMID- 24327234
TI  - Qualitative and quantitative evaluation of human dental enamel after bracket
      debonding: a noncontact three-dimensional optical profilometry analysis.
AB  - OBJECTIVES: The aim of this study was to undertake a qualitative and quantitative
      evaluation of changes on enamel surfaces after debonding of brackets followed by
      finishing procedures, using a high-resolution three-dimensional optical profiler
      and to investigate the accuracy of the technique. MATERIALS AND METHODS: The
      labial surfaces of 36 extracted upper central incisors were examined. Before
      bonding, the enamel surfaces were subjected to profilometry, recording four
      amplitude parameters. Brackets were then bonded using two types of light-cured
      orthodontic adhesive: composite resin and resin-modified glass ionomer cement.
      Finishing was performed by three different methods: pumice on a rubber cup, fine
      and ultrafine aluminum oxide discs, and microfine diamond cups followed by
      silicon carbide brushes. The samples were subsequently re-analyzed by
      profilometry. RESULTS: Wilcoxon signed-rank test, Kruskal-Wallis test (p < 0.05)
      and a posteriori Mann-Whitney U test with Bonferroni correction (p < 0.0167)
      revealed a significant reduction of enamel roughness when diamond cups followed
      by silicon carbide brushes were used to finish surfaces that had remnants of
      resin-modified glass ionomer adhesive and when pumice was used to finish surfaces
      that had traces of composite resin. Enamel loss was minimal. CONCLUSIONS: The 3D
      optical profilometry technique was able to provide accurate qualitative and
      quantitative assessment of changes on the enamel surface after debonding.
      CLINICAL RELEVANCE: Morphological changes in the topography of dental surfaces,
      especially if related to enamel loss and roughness, are of considerable clinical
      importance. The quantitative evaluation method used herein enables a more
      comprehensive understanding of the effects of orthodontic bonding on teeth.

PMID- 24327235
TI  - Treatment effect of ozone and fluoride varnish application on occlusal caries in
      primary molars: a 12-month study.
AB  - AIM: The aim of this study is to evaluate the effect of ozone and fluoride
      varnish on occlusal caries in primary molars in a split-mouth study. MATERIALS
      AND METHODS: Caries risk was estimated by treating Public Dental Health Service
      dentists. Children with occlusal caries with Ekstrand index scores <=3 (VI <=3)
      were included. Selection of caries lesions was discontinued for ethical reasons
      due to non-acceptable clinical results during the follow-up. In the continued
      evaluation pairs of teeth with non-cavitated caries lesions, Ekstrand score <=2a
      (VI <=2) were selected. Fifty pairs of carious primary molars were included, 18
      boys and 15 girls (mean 4.7 years, range 3-8). At baseline, the lesions were
      assessed by visual inspection (VI) and laser-induced fluorescence (LF), in each
      pair to treatment with 40 s ozone (HealOzone(TM), 2,100 ppm) or fluoride varnish
      Duraphat(r). The treatments and evaluations were repeated at 3, 6 9 months and
      evaluations only at 12 months. RESULTS: Medium-high caries risk was observed in
      VI <=3 children and low-medium risk in VI <=2a children. In the 15 pairs VI <=3
      lesions, 8 treated with ozone and 9 with fluoride progressed to failure. In the
      35 pairs VI <=2a lesions, one lesion failed. Median baseline LF values in the VI
      <=3 group were 76 and 69, for ozone and fluoride lesions, respectively, and 21
      and 19 in the VI <=2a group. At 12 months, LF values in the VI <=2a group were 15
      and 18. No improvement or difference in LF values was found over time between the
      caries lesions treated with ozone or fluoride. CONCLUSIONS: Neither ozone nor
      fluoride varnish treatments stopped the progression of caries in cavitated
      lesions. In low and medium caries risk children, non-cavitated lesions following
      both treatments showed slight or no progression. The use of ozone or fluoride
      varnish treatments in this regime as caries preventive method, added to the daily
      use of fluoridated toothpaste, to arrest caries progression in primary molars
      must therefore be questioned.

PMID- 24327236
TI  - Using the low-pass monogenic signal framework for cell/background classification
      on multiple cell lines in bright-field microscope images.
AB  - PURPOSE: Several cell detection approaches which deal with bright-field
      microscope images utilize defocusing to increase image contrast. The latter is
      related to the physical light phase through the transport of intensity equation
      (TIE). Recently, it was shown that it is possible to approximate the solution of
      the TIE using a low-pass monogenic signal framework. The purpose of this paper is
      to show that using the local phase of the aforementioned monogenic signal instead
      of the defocused image improves the cell/background classification accuracy.
      MATERIALS AND METHODS: The paper statement was tested on an image database
      composed of three cell lines: adherent CHO, adherent L929, and Sf21 in
      suspension. Local phase and local energy images were generated using the low-pass
      monogenic signal framework with axial derivative images as input. Machine
      learning was then employed to investigate the discriminative power of the local
      phase. Three classifier models were utilized: random forest (RF), support vector
      machine (SVM) with a linear kernel, and SVM with a radial basis function (RBF)
      kernel. RESULTS: The improvement, averaged over cell lines, of classifying 5*5
      sized patches extracted from the local phase image instead of the defocused image
      was 7.3% using the RF, 11.6% using the linear SVM, and 10.2% when a RBF kernel
      was employed instead of the linear one. Furthermore, the feature images can be
      sorted by increasing discriminative power as follows: at-focus signal, local
      energy, defocused signal, local phase. The only exception to this order was the
      superiority of local energy over defocused signal for suspended cells.
      CONCLUSIONS: Local phase computed using the low-pass monogenic signal framework
      considerably outperforms the defocused image for the purpose of pixel-patch
      cell/background classification in bright-field microscopy.

PMID- 24327237
TI  - Reporting a population pharmacokinetic-pharmacodynamic study: a journal's
      perspective.
AB  - The key purpose of performing pharmacometric research is to aid optimization of
      drug dosing strategies. The statistical techniques required for this research are
      advanced, which can make interpretation of results difficult to convey to the
      target audience if they are unfamiliar with pharmacometric concepts. This article
      provides a basic guide for authors who wish to publish pharmacometric analyses in
      peer-reviewed journals. This guide is intended to enhance the readability,
      reproducibility and understanding of the work for a general readership, which may
      include clinicians, pharmacists and pharmacometricians. Presentation techniques
      and examples are offered, as well as a checklist of suggested contents for the
      manuscript. 

PMID- 24327241
TI  - Nasal septal reconstruction.

PMID- 24327240
TI  - Measuring the displacement and replacement of government health expenditure.
AB  - Research assessing the relationship between government health expenditure and
      development assistance for health channeled to governments (DAHG) has not
      considered that this relationship may depend on whether DAHG is increasing or
      decreasing. We explore this issue using general method of moments estimation and
      a panel of financial flows data spanning 119 countries and 16 years. Our primary
      concern is how DAHG affects government health expenditure as source (GHES). We
      disaggregate the average effect of DAHG and separately identify the effects of
      increases versus decreases in DAHG. We find that a $1 year-over-year increase in
      DAHG leads to a $0.62 (90% confidence interval (CI): 0.15, 1.09) decrease in
      GHES, whereas a $1 year-over-year decrease in DAHG does not have an effect on
      GHES that is statistically different from zero (CI: -0.67, 1.17). Simulation
      shows that the displacement of GHES between 1995 and 2010 reduced total
      government health expenditure by $152.8 billion (CI: 46.9, 277.6). Moreover, the
      irregular disbursement of DAHG reduced total government expenditure by $96.9
      billion (CI: 0.5, 212.4). Thus, this research shows that health aid is fungible
      and highlights the cost of displacement and erratic aid disbursement.

PMID- 24327239
TI  - The 60- and 70-kDa heat-shock proteins and their correlation with cardiovascular
      risk factors in postmenopausal women with metabolic syndrome.
AB  - We investigated the association between circulating levels of 60 and 70 kDa heat
      shock proteins (HSP60 and 70) and cardiovascular risk factors in postmenopausal
      women with or without metabolic syndrome (MetS). This cross-sectional study
      included 311 Brazilian women (age >=45 years with amenorrhea >=12 months). Women
      showing three or more of the following diagnostic criteria were diagnosed with
      MetS: waist circumference (WC) >=88 cm, blood pressure >=130/85 mmHg,
      triglycerides >=150 mg/dl, high-density lipoprotein (HDL) <50 mg/dl, and glucose
      >=100 mg/dl. Clinical, anthropometric, and biochemical parameters were collected.
      HSP60, HSP70, antibodies to HSP60 and HSP70, and C-reactive protein (CRP) levels
      were measured in serum. Student's t test, Kruskal-Wallis test, chi-square test,
      and Pearson correlation were used for statistical analysis. Of the 311 women,
      30.9 % (96/311) were diagnosed with MetS. These women were, on average, obese
      with abdominal fat deposition and had lower HDL values as well as higher
      triglycerides and glucose levels. Homeostasis model assessment-insulin resistant
      (HOMA-IR) test values in these women were compatible with insulin resistance (P <
      0.05). CRP and HSP60 concentrations were higher in women with MetS than in women
      without MetS (P < 0.05). HSP60, anti-HSP70, and CRP concentrations increased with
      the number of features indicative of MetS (P < 0.05). There was a significant
      positive correlation between anti-HSP70 and WC, blood pressure and HOMA-IR, and
      between CRP and WC, blood pressure, glucose, HOMA-IR, and triglycerides (P <
      0.05). In postmenopausal women, serum HSP60 and anti-HSP70 concentrations
      increased with accumulating features of the metabolic syndrome. These results
      suggest a greater immune activation that is associated with cardiovascular risk
      in postmenopausal women with metabolic syndrome. 

PMID- 24327238
TI  - How accurate and precise are limited sampling strategies in estimating exposure
      to mycophenolic acid in people with autoimmune disease?
AB  - Mycophenolic acid (MPA) is a potent immunosuppressant agent, which is
      increasingly being used in the treatment of patients with various autoimmune
      diseases. Dosing to achieve a specific target MPA area under the concentration
      time curve from 0 to 12 h post-dose (AUC12) is likely to lead to better treatment
      outcomes in patients with autoimmune disease than a standard fixed-dose strategy.
      This review summarizes the available published data around concentration
      monitoring strategies for MPA in patients with autoimmune disease and examines
      the accuracy and precision of methods reported to date using limited
      concentration-time points to estimate MPA AUC12. A total of 13 studies were
      identified that assessed the correlation between single time points and MPA AUC12
      and/or examined the predictive performance of limited sampling strategies in
      estimating MPA AUC12. The majority of studies investigated mycophenolate mofetil
      (MMF) rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation of
      MPA. Correlations between MPA trough concentrations and MPA AUC12 estimated by
      full concentration-time profiling ranged from 0.13 to 0.94 across ten studies,
      with the highest associations (r (2) = 0.90-0.94) observed in lupus nephritis
      patients. Correlations were generally higher in autoimmune disease patients
      compared with renal allograft recipients and higher after MMF compared with EC
      MPS intake. Four studies investigated use of a limited sampling strategy to
      predict MPA AUC12 determined by full concentration-time profiling. Three studies
      used a limited sampling strategy consisting of a maximum combination of three
      sampling time points with the latest sample drawn 3-6 h after MMF intake, whereas
      the remaining study tested all combinations of sampling times. MPA AUC12 was best
      predicted when three samples were taken at pre-dose and at 1 and 3 h post-dose
      with a mean bias and imprecision of 0.8 and 22.6 % for multiple linear regression
      analysis and of -5.5 and 23.0 % for maximum a posteriori (MAP) Bayesian analysis.
      Although mean bias was less when data were analysed using multiple linear
      regression, MAP Bayesian analysis is preferable because of its flexibility with
      respect to sample timing. Estimation of MPA AUC12 following EC-MPS administration
      using a limited sampling strategy with samples drawn within 3 h post-dose
      resulted in biased and imprecise results, likely due to a longer time to reach a
      peak MPA concentration (t max) with this formulation and more variable
      pharmacokinetic profiles. Inclusion of later sampling time points that capture
      enterohepatic recirculation and t max improved the predictive performance of
      strategies to predict EC-MPS exposure. Given the considerable pharmacokinetic
      variability associated with mycophenolate therapy, limited sampling strategies
      may potentially help in individualizing patient dosing. However, a compromise
      needs to be made between the predictive performance of the strategy and its
      clinical feasibility. An opportunity exists to combine research efforts globally
      to create an open-source database for MPA (AUC, concentrations and outcomes) that
      can be used and prospectively evaluated for AUC target-controlled dosing of MPA
      in autoimmune diseases.

PMID- 24327242
TI  - A new documentation standard in the nose examination: SL classification.
AB  - The goal of this article is to present a system for standardized documentation of
      the findings obtained during the examination of the nose. Three levels of data
      recording have been established for various purposes: (1) First level: Septum
      lateral nasal wall (SL) classification, (2) Second level: SL classification
      including seven drawings, (3) Third level: SL classification including seven
      drawings and a detailed questionnaire. The first level was found to be a fast,
      easy, and standard way to document the findings of the nose examination which
      facilitated follow-up as well. The addition of graphics enhanced its informative
      power at the second level. The third level helped to describe the proper status
      of the nose in detail before and after septoplasty which was invaluable for
      follow-up, statistical analysis, self-education, and self-assessment. 

PMID- 24327243
TI  - Segmental reconstruction for nasal septal deviation.
AB  - The management of septal deviations is one of the major challenges for the
      surgeon due to variability of the etiology of nasal obstruction. In parallel with
      the advances in rhinoplasty techniques during the last three decades, the
      treatment options for septal deviation increased tremendously. In this article, a
      new anatomical and virtual division of the nasal septum known as "segmental
      division" is proposed. Additionally, the management of deviations in the caudal
      and/or dorsal segment is presented. In traumatic and revision cases, more
      difficult techniques necessitating the harvesting of conchal or costal cartilages
      are also demonstrated. 

PMID- 24327244
TI  - Use of polydioxanone plate in septal reconstruction.
AB  - Septal reconstruction is challenging. Autologous cartilage may be thin or
      deviated and traditional techniques are often inadequate or technically
      difficult. The use of an absorbable scaffold material for support during healing
      can improve results. Polydioxanone (PDS) plate can be used for this purpose. We
      describe our use of PDS plate in both open and closed septal surgeries, as well
      as in the repair of septal perforations. Surgical techniques and potential
      complications are discussed. The current evidence for PDS plate is reviewed. PDS
      plate is a safe and reliable absorbable implant that has many different
      applications in septal surgery and reconstruction. It not only acts as a scaffold
      but also stimulates and guides cartilage regeneration. 

PMID- 24327245
TI  - Bone recycling in nasal septal reconstruction.
AB  - Septal reconstruction alone or together with rhinoplasty can be a very
      challenging operation. In situations where septal cartilage is used for grafting
      or is not enough, bony implants taken from the perpendicular plate of the ethmoid
      and vomer can be used as a filler material between the mucoperichondrial flaps to
      avoid from unwanted mucosal atrophy, flapping, and septal perforation. These bony
      implants can also be used for splinting the dorsal and/or caudal segment of the
      septal cartilage after reshaping by rongeurs. On rare occasions, they can even be
      used for subtotal reconstruction of the septum. 

PMID- 24327246
TI  - Subtotal septal reconstruction by using conchal graft.
AB  - Loss of the cartilaginous nasal septum, a condition frequently encountered in the
      practice of nasal surgery, can vary in scale depending on its etiopathogenesis.
      Previous surgery, trauma, and infection can lead to subtotal absence of the
      septum with severe functional and aesthetic problems. Use of the auricular concha
      for reconstructive purposes proves an immediate and effective method making it
      possible to replace the missing tissue without involving operations of a more
      invasive nature. The fundamental problem in the use of the auricular concha is
      making this type of cartilage as similar as possible to the cartilaginous septum,
      endowing it with the structural strength and straightness required for support
      and the respiratory function. Surgical procedures with the use of figure-eight
      sutures and grafts of cartilage harvested from the concha prove capable of
      performing this major task of morphofunctional transformation. The article
      describes the phases involved in achieving the set objectives. 

PMID- 24327247
TI  - Oblique split technique in septal reconstruction.
AB  - The septum is considered to be the most important anatomical structure in
      providing nasal support. Because of a variety of potential etiologies nasal
      septum could be severely deformed or even diminished. Autogenous cartilage has
      generally been considered the gold standard grafting material in reconstructive
      septal surgery for creating the infrastructure of the nose. In the restructuring
      of the nasal skeleton autogenous cartilage can be harvested from the auricle or
      the rib. For the major septal problems requiring a large volume of tissues with
      severe structural defects costal cartilage is considered the best graft material.
      Apart from its advantages, warping has been the main problem with costal
      cartilage grafting. Oblique split method, provides straight costal cartilage
      grafts of varying thicknesses without the risk of warping. Segmental
      reconstruction of the L-strut with oblique split method, composed of dorsal and
      caudal struts, enables fine adjustment of height of the reconstructed septum. 

PMID- 24327248
TI  - Subtotal septal reconstruction: an update.
AB  - Subtotal septal reconstruction is a surgical technique used to reconstruct severe
      septal deviations that are not easily repaired using less invasive methods.
      Patients with identifiable septal fractures across the caudal or dorsal segments
      of the L-strut are good candidates. These patients may present with deformities
      such as the deviated nose or saddle nose. Adequate autologous cartilage is needed
      to reconstruct the septum. The deviated segments of the nasal septum are removed
      and then reconstructed by replacing the caudal septum with a straight piece of
      septal cartilage fixated to the nasal spine. The bilateral extended spreader
      grafts fixated to the remnant dorsal strut is then fixed to the caudal septal
      replacement graft to reconstitute the L-strut. In some cases, the dorsal strut
      may overlap the caudal portion of the L-strut to complete the repair. Care must
      be taken in setting nasal length, projection, rotation, and supratip break. If
      these parameters are not set very carefully deformity may ensue. Other potential
      complications include change in the upper lip smile or a crease forming in the
      upper lip when the patient smiles. This is a complex technique and must be
      performed with special care to avoid deformity. 

PMID- 24327249
TI  - Analysis of cartilage-polydioxanone foil composite grafts.
AB  - This study presents an analytical investigation into the mechanical behavior of a
      cartilage-polydioxanone (PDS) plate composite grafts. Numerical methods are used
      to provide a first-order, numerical model of the flexural stiffness of a
      cartilage-PDS graft. Flexural stiffness is a measure of resistance to bending and
      is inversely related to the amount of deformation a structure may experience when
      subjected to bending forces. The cartilage-PDS graft was modeled as a single
      composite beam. Using Bernoulli-Euler beam theory, a closed form equation for the
      theoretical flexural stiffness of the composite graft was developed. A parametric
      analysis was performed to see how the flexural properties of the composite model
      changed with varying thicknesses of PDS foil. The stiffness of the cartilage-PDS
      composite using 0.15-mm-thick PDS was four times higher than cartilage alone. The
      composite with a 0.5-mm-thick PDS graft was only 1.7 times stiffer than the
      composite with the 0.15-mm-thick PDS graft. Although a thicker graft material
      will yield higher flexural stiffness for the composite, the relationship between
      composite stiffness and PDS thickness is nonlinear. After a critical point,
      increments in graft thickness produce gradually smaller improvements in flexural
      stiffness. The small increase in stiffness when using the thicker PDS foils
      versus the 0.15 mm PDS foil may not be worth the potential complications
      (prolonged foreign body reaction, reduction in nutrient diffusion to cartilage)
      of using thicker artificial grafts.

PMID- 24327250
TI  - A new classification of spreader flap techniques.
AB  - The objective of this study was to introduce various spreader flap technique
      modifications to adjust the width of the middle nasal vault in patients who
      underwent rhinoplasties with humpectomy. Decisive modifications of current
      spreader flap techniques were performed to allow a more natural restoration of
      the middle nasal vault and the internal nasal valve after humpectomy. Additional
      steps provide tools to adjust the width and shape of the middle nasal vault
      according to patients' requirements. The techniques were categorized into "basic
      spreader flaps," "flaring spreader flaps," "support spreader flaps," and
      "interrupted spreader flaps." The various spreader flap techniques were used
      during 576 primary septorhinoplasties in patients with hump noses, hump/crooked
      noses, or hump/tension noses. The average follow-up was 19 months. Patients who
      received basic spreader flaps or a flaring spreader flaps tended to show a
      slightly too wide middle nasal vault, revision surgery was necessary in four of
      these cases. All other patients showed an appropriate width in the middle nasal
      vault and an aesthetically pleasing course of the dorsal aesthetic lines. No
      signs of inverted v deformities or collapse of the internal nasal valve were
      observed in any of the patients. Patients who had reported impaired nasal
      breathing preoperatively described clearly improved subjective symptoms. The
      described techniques appear to be appropriate and highly promising as a
      supplement to existing procedures for reconstructing the middle nasal vault and
      internal nasal valves. No additional cartilage grafts are needed. 

PMID- 24327251
TI  - Spreader graft in closed rhinoplasty: the "rail spreader".
AB  - Spreader grafts (SGs) have been widely used for both aesthetic and functional
      reasons to prevent middle vault collapse and treat internal nasal valve
      insufficiency. Although SG precise fixation can be easily achieved in open
      rhinoplasty, the difficulties of SG placement in closed rhinoplasties can be
      discouraging. In the present report, we describe a new custom-made SG (called
      "rail spreader") and the personal easy method of application of such graft in
      "endonasal" rhinoplasty. The technical details and results are reported along
      with the advantages of our technique over previously described approaches. 

PMID- 24327252
TI  - Stahl ear correction using the third crus cartilage flap.
AB  - Stahl ear is usually associated with the existence of a third crus that traverses
      the scapha. The absence of the superior crus of the antihelix, a broadened
      scapha, and unfolded, long helical rim may contribute to the formation of the
      deformity. The method presented in this article is a combined technique intended
      to recreate the absent superior crus using the third crus as a cartilage flap
      along with elimination of the third crus, reducing the scapha size, and
      correcting helical rim deformities by skin and cartilage excisions. One bilateral
      and three unilateral cases were operated on with this technique (five auricles).
      The first unilateral cases were performed without scapha reduction and helix
      correction which was used in the other three cases with successful results. This
      procedure can be used to correct Stahl ear variations in the case of an absent
      superior crus when a third crus is present, the scapha is of increased size, and
      the helix is long without a fold. 

PMID- 24327253
TI  - Entangler via electromagnetically induced transparency with an atomic ensemble.
AB  - Quantum entanglement plays an essential role in quantum information processing
      and quantum networks. One of the commonly-used methods to generate multiple
      entangled fields is to employ polarizing beam splitters. However, nonclassical
      input light fields are required and the generated entangled fields are always
      degenerate in such case. Here, we present a proof-of-principle demonstration of
      an efficient and convenient way to entangle multiple light fields via
      electromagnetically induced transparency (EIT) in an atomic ensemble. The atomic
      spin wave, produced through EIT in the Lambda-type atomic system, can be
      described by a Bose operator and can act as an entangler. With such an entangler,
      any desired number of nondegenerate narrow-band continuous-variable entangled
      fields, in principle, can be generated through stimulated Raman scattering
      processes. This scheme holds great promise for applications in scalable quantum
      communication and quantum networks. PACS: 42.50.Gy, 03.67.Bg, 42.50.Dv, 42.65.Lm.

PMID- 24327254
TI  - SAR news.

PMID- 24327255
TI  - The analysis of enhancement pattern of hepatic inflammatory pseudotumor on
      contrast-enhanced ultrasound.
AB  - OBJECTIVE: The aim of this study was to assess the role of contrast-enhanced
      ultrasound (CEUS) in the characterization of hepatic inflammatory pseudotumor
      (IPT). METHODS: We retrospectively reviewed 36 cases of histopathologically
      diagnosed IPT. Nodule enhancement appearances during the arterial, portal, and
      delayed phases were defined as hyperenhancement, isoenhancement, hypoenhancement,
      and non-enhancement compared with the surrounding liver parenchyma. Statistical
      analysis was performed by the one-way ANOVA and chi (2) tests. RESULTS: Among
      total 36 cases, 7 nodules were absent of contrast enhancement during all three
      phrases on CEUS. Twenty-nine nodules appeared different forms of enhancement in
      arterial phase. Diffuse homogeneous hyperenhancement, diffuse heterogeneous
      hyperenhancement, peripheral rim-like enhancement, and diffuse iso-enhancement
      were found in 10, 12, 5, and 2 of the nodules, respectively. Twenty-five nodules
      showed hypoenhancement in portal and delayed phases. Four nodules showed contrast
      washed out synchronously with normal liver parenchyma. The median time to
      enhancement, median time to peak, and median time to wash out of the nodules were
      17 s (range 11-28 s), 23 s (range 14-42 s), and 45 s (range 23-100 s),
      respectively. No statistical significant differences were found in the above
      parameters of nodule enhancement and proportion of enhancement patterns when
      dividing the nodules into subgroups by nodule size. CONCLUSION: IPT displays a
      variety of enhancement patterns due to pathological changes in the course of
      disease progression. Some characteristics on CEUS may be helpful in the
      differential diagnosis of IPT.

PMID- 24327257
TI  - CD24 mediates gastric carcinogenesis and promotes gastric cancer progression via
      STAT3 activation.
AB  - The development of gastric cancer (GC) is a complex multistep process, including
      numerous genetic and epigenetic changes. CD24 is associated with enhanced
      invasiveness of GC and a poor prognosis. However, the mechanism by which CD24
      induces GC progression remains poorly characterized. Here, we found that the
      expression of CD24 gradually increased in samples of normal gastric mucosa, non
      atrophic chronic gastritis, chronic atrophic gastritis (CAG), CAG with intestinal
      metaplasia, dysplasia and GC. Moreover, the knockdown of CD24 induced significant
      levels of apoptosis in GC cells via the mitochondrial apoptotic pathway. CD24 may
      also promote cellular invasion and regulate the expression of E-cadherin,
      fibronectin and vitamin D receptor in GC cells. The activation of signal
      transducer and activator of transcription 3 (STAT3) may mediate CD24-induced GC
      survival and invasion in vitro. Furthermore, CD24-induced GC progression and
      STAT3 activation could also be detected in vivo and in clinical GC tissues
      samples. Taken together, our results indicate that CD24 mediates gastric
      carcinogenesis and may promote GC progression by suppressing apoptosis and
      promoting invasion, with the activation of STAT3 playing a critical role. 

PMID- 24327259
TI  - Effect of a mutagenized acyl-ACP thioesterase FATA allele from sunflower with
      improved activity in tobacco leaves and Arabidopsis seeds.
AB  - The substrate specificity of the acyl-acyl carrier protein (ACP) thioesterases
      significantly determines the type of fatty acids that are exported from plastids.
      Thus, designing acyl-ACP thioesterases with different substrate specificities or
      kinetic properties would be of interest for plant lipid biotechnology to produce
      oils enriched in specialty fatty acids. In the present work, the FatA
      thioesterase from Helianthus annuus was used to test the impact of changes in the
      amino acids present in the binding pocket on substrate specificity and catalytic
      efficiency. Amongst all the mutated enzymes studied, Q215W was especially
      interesting as it had higher specificity towards saturated acyl-ACP substrates
      and higher catalytic efficiency compared to wild-type H. annuus FatA. Null, wild
      type and high-efficiency alleles were transiently expressed in tobacco leaves to
      check their effect on lipid biosynthesis. Expression of active FatA thioesterases
      altered the composition of leaf triacylglycerols but did not alter total lipid
      content. However, the expression of the wild type and the high-efficiency alleles
      in Arabidopsis thaliana transgenic seeds resulted in a strong reduction in oil
      content and an increase in total saturated fatty acid content. The role and
      influence of acyl-ACP thioesterases in plant metabolism and their possible
      applications in lipid biotechnology are discussed. 

PMID- 24327260
TI  - Enzymatic characterization of a glycoside hydrolase family 5 subfamily 7 (GH5_7)
      mannanase from Arabidopsis thaliana.
AB  - Each plant genome contains a repertoire of beta-mannanase genes belonging to
      glycoside hydrolase family 5 subfamily 7 (GH5_7), putatively involved in the
      degradation and modification of various plant mannan polysaccharides, but very
      few have been characterized at the gene product level. The current study presents
      recombinant production and in vitro characterization of AtMan5-1 as a first step
      towards the exploration of the catalytic capacity of Arabidopsis thaliana beta
      mannanase. The target enzyme was expressed in both E. coli (AtMan5-1e) and P.
      pastoris (AtMan5-1p). The main difference between the two forms was a higher
      observed thermal stability for AtMan5-1p, presumably due to glycosylation of that
      particular variant. AtMan5-1 displayed optimal activity at pH 5 and 35  degrees C
      and hydrolyzed polymeric carob galactomannan, konjac glucomannan, and spruce
      galactoglucomannan as well as oligomeric mannopentaose and mannohexaose. However,
      the galactose-rich and highly branched guar gum was not as efficiently degraded.
      AtMan5-1 activity was enhanced by Co(2+) and inhibited by Mn(2+). The catalytic
      efficiency values for carob galactomannan were 426.8 and 368.1 min(-1) mg(-1) mL
      for AtMan5-1e and AtMan5-1p, respectively. Product analysis of AtMan5-1p
      suggested that at least five substrate-binding sites were required for manno
      oligosaccharide hydrolysis, and that the enzyme also can act as a
      transglycosylase.

PMID- 24327258
TI  - Drug repositioning: playing dirty to kill pain.
AB  - The number of approved new molecular entity drugs has been decreasing as the
      pharmaceutical company investment in research and development is increasing. As
      we face this painful crisis, called an innovation gap, there is increasing
      awareness that development of new uses of existing drugs may be a powerful tool
      to help overcome this obstacle because it takes too long, costs too much and can
      be risky to release drugs developed de novo. Consequently, drug repositioning is
      emerging in different therapeutic areas, including the pain research area.
      Worldwide, pain is the main reason for seeking healthcare, and pain relief
      represents an unmet global clinical need. Therefore, development of analgesics
      with better efficacy, safety and cost effectiveness is of paramount importance.
      Despite the remarkable advancement in research on cellular and molecular
      mechanisms underlying pain pathophysiology over the past three decades, target
      based therapeutic opportunities have not been pursued to the same extent.
      Phenotypic screening remains a more powerful tool for drug development than
      target-based screening so far. It sounds somewhat heretical, but some multi
      action drugs, rather than very selective ones, have been developed intentionally.
      In the present review, we first critically discuss the utility of drug
      repositioning for analgesic drug development and then show examples of 'old'
      drugs that have been successfully repositioned or that are under investigation
      for their analgesic actions. We conclude that drug repositioning should be more
      strongly encouraged to help build a bridge between basic research and pain relief
      worldwide. 

PMID- 24327261
TI  - The human dark side: evolutionary psychology and original sin.
AB  - Human nature has a dark side, something important to religions. Evolutionary
      psychology has been used to illuminate the human shadow side, although as a
      discipline it has attracted criticism. This article seeks to examine the
      evolutionary psychology's understanding of human nature and to propose an
      unexpected dialog with an enduring account of human evil known as original sin.
      Two cases are briefly considered: murder and rape. To further the exchange,
      numerous theoretical and methodological criticisms and replies of evolutionary
      psychology are explored jointly with original sin. Evolutionary psychology can
      partner with original sin since they share some theoretical likenesses and
      together they offer insights into the nature of what it means to be human. 

PMID- 24327262
TI  - Facile one-pot fabrication of hollow porous silica nanoparticles.
AB  - A method for the fabrication of hollow silica nanospheres, a facile one-pot
      hydrothermal route, is described. Heating of an aqueous solution of water glass
      and D-glucose to 180  degrees C for 24 h affords-as indicated by transmission
      electron microscopy-a nanospherical composite consisting of a silica shell
      sheathing a carbonaceous core. Subsequent removal of the carbonaceous interior
      through oxidation in air produces hollow silica structures. Variation of the
      concentration of the two jointly dissolved chemicals enables a variation of the
      thickness of the silica shell. The hollow silica particles were characterized by
      means of SEM, TEM, XRD, IR spectroscopy, thermogravimetrical analysis (TGA), and
      sorption measurements. 

PMID- 24327263
TI  - Sesamoiditis of the cyamella: imaging features of this rare presentation.
AB  - We report a unique case of sesamoiditis in an extremely rare accessory genicular
      ossicle. Common to lower primates, the cyamella or popliteus tendon sesamoid bone
      is usually absent in humans. A 19-year-old male sustained a twisting injury to
      the right knee and presented with mechanical symptoms of knee pseudo-locking. A
      plain radiograph of the knee illustrated the presence of a cyamella. Magnetic
      resonance imaging demonstrated marked bone marrow oedema of this sesamoid
      structure and in the adjacent popliteus tendon. To our knowledge, documented
      sesamoiditis of this osseous structure on radiological imaging has not been
      published in English literature and this case highlights the imaging features of
      this uncommon entity. 

PMID- 24327264
TI  - Inter-layer charge disproportionation in the dual-layer organic metal (tTTF
      I)2ClO4 with unsymmetrical I...O halogen bond interactions.
AB  - A mixed-valence salt of tTTF-I with ClO4(-), formulated as (tTTF-I)2ClO4, is
      characterized by the presence of two crystallographically independent donor
      molecules, segregated in different layers and linked together through I...O
      interactions with the ClO4(-) anion disordered at room temperature. The tTTF-I
      donor molecule was prepared by metallation of tTTF (trimethylene
      tetrathiafulvalene) followed by reaction with iodine to afford the mono and
      diiodo derivatives tTTF-I and tTTFI2, respectively. The crystal structure of the
      latter neutral tTTFI2 shows the occurrence of strong type II, II halogen bond
      interactions. Band structure calculations of the dual-layer structure of the 2 :
      1 salt (tTTF-I)2ClO4 show co-existence of both 1D open and 2D closed Fermi
      surfaces. The salt undergoes a metal-insulator phase transition at T(MI) = 90 K,
      associated with an electronic dimensionality decrease, since already at 100 K,
      the 2D part of the Fermi surface transforms into 1D corrugated planes. High
      resolution X-ray investigations performed at 100 K, combined with multipolar
      refinements, indicate an approximately equivalent +0.5e charge in both donor
      molecules, as also deduced from the intramolecular bond distances. On the other
      hand, Raman spectroscopic investigations show that at ambient temperature the
      charge is actually distributed non-uniformly in conducting layers of tTTF-I
      molecules, with the identification of molecules with charges +1, +0.5, 0e, while
      at low temperature the charge distribution becomes essentially uniform (+0.5e),
      as confirmed from the X-ray high resolution data. These apparently contradictory
      behaviors are actually a consequence of a partial electron transfer between the
      two independent slabs to reach a common Fermi level in the metallic phase.

PMID- 24327265
TI  - Lipid-lowering agents for nephrotic syndrome.
AB  - BACKGROUND: Nephrotic syndrome is the collective name given to a group of
      symptoms that include proteinuria, lipiduria, hypoalbuminaemia, oedema,
      hypercholesterolaemia, elevated triglycerides, and hyperlipidaemia.
      Hyperlipidaemia is thought to aggravate glomerulosclerosis (hardening of blood
      vessels in the kidneys) and enhance progression of glomerular disease. Studies
      have established that reduction in total cholesterol and low density lipoprotein
      (LDL) cholesterol is associated with reduction in risk of cardiovascular
      diseases. In 2011, the European Society of Cardiology and European
      Atherosclerosis Society guidelines for the management of dyslipidaemia
      recommended use of statins as first-line agents in the management of nephrotic
      dyslipidaemia. However, the effectiveness and safety of statins for people with
      nephrotic syndrome remains uncertain. Furthermore, the efficacy of second-line
      lipid-lowering drugs, such as ezetimibe and nicotinic acid, has not been proven
      in patients with nephrotic syndrome who are unable to tolerate statin therapy.
      OBJECTIVES: This review aimed to evaluate the benefits and harms of lipid
      lowering agents in adults and children with nephrotic syndrome. SEARCH METHODS:
      We searched the Cochrane Renal Group's Specialised Register (to 18 March 2013)
      through contact with the Trials Search Co-ordinator using search terms relevant
      to this review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and
      quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation,
      use of alternate medical records, date of birth or other predictable methods)
      looking at participants with nephrotic syndrome that compared any lipid-lowering
      agent to placebo, no treatment or other lipid-lowering agents, given for not less
      than four weeks, were included. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed study eligibility and risk of bias, and extracted data.
      Statistical analyses were performed using a random effects model. Dichotomous
      results were expressed as risk ratios (RR) with 95% confidence intervals (CI).
      For continuous measures mean difference (MD) was used, or the standardised mean
      difference (SMD) where different scales had been used. MAIN RESULTS: We included
      five RCTs enrolling a total of 203 participants. Of these, four studies compared
      statins with no treatment or placebo, and one compared fibrates with placebo. We
      found no published studies comparing second-line agents such as ezetimibe, bile
      acid sequestrants, and nicotinic acid with placebo or no treatment. Our
      assessment of the risk of bias found that one study was judged overall to be at
      low risk of bias and the remaining four were judged to be at high risk of
      bias.Most outcomes were supported by single study data. One study reported
      significantly increased high density lipoprotein (HDL) cholesterol among
      participants in the statin arm compared with the no treatment group (MD 5.40
      mg/dL, 95% CI 2.31 to 8.49). Another study reported higher serum albumin in the
      statin group compared to those who received no treatment (MD 0.60 g/dL, 95% CI
      0.14 to 1.06). No serious adverse events, such as rhabdomyolysis, were reported,
      however some minor events occurred. One study reported no significant difference
      in the number of participants with elevated liver enzymes (RR 3.00, 95% CI 0.13
      to 69.52); three studies reported liver enzymes remained within the normal range
      (no data provided). Four studies reported creatinine phosphokinase (CPK). One
      study indicated that CPK values fluctuated in both the simvastatin and placebo
      groups (no data provided); the remaining three studies reported CPK either stayed
      within the normal range (one study) or there was no significant difference
      between the lipid lowering agents and placebo. AUTHORS' CONCLUSIONS: None of the
      included studies reported patient-centred outcomes including all-cause mortality,
      cardiovascular mortality, or non-fatal myocardial infarction; only single studies
      reported cholesterol (HDL, LDL and total cholesterol), triglycerides, serum
      creatinine, blood urea nitrogen, liver enzymes, and protein (serum, urine). High
      quality RCTs need to be conducted to assess the safety and efficacy of lipid
      lowering drugs for people with nephrotic syndrome.

PMID- 24327266
TI  - Psychopathic-like traits in detained adolescents: clinical usefulness of self
      report.
AB  - Studies have demonstrated that self-report tools can be used to reliably and
      validly examine psychopathic-like traits in adolescents. However, it is unclear
      if self-report instruments are still reliable and valid when confidentiality
      cannot be guaranteed, such as during routine assessments in juvenile detention
      centres. To address this issue, the current study used data from the routine
      mental health screening of 365 detained male adolescents (12-18 years) in two
      juvenile detention centres. With the intention of gaining insight in the clinical
      usefulness of self-reported psychopathic-like traits, we examined relations known
      from literature with emotional and behavioural features. Self-reported
      psychopathic-like traits, measured by the Youth Psychopathic Traits Inventory
      Short version (YPI-S), were uniquely associated with substance abuse,
      anger/irritability, conduct problems and hyperactivity, but not with
      internalizing problems. YPI-S-dimensions showed several specific relationships
      with variables of interest. For example, only the callous unemotional dimension
      was negatively related with prosocial behaviour and only the behavioural
      dimension was positively related with hyperactivity. In conclusion, self-reported
      psychopathic-like traits showed expected relations with relevant variables. These
      findings suggest that self-report can be used to identify detained youths with
      high levels of psychopathic-like traits outside a research context, thus, even
      when anonymity and confidentiality are not guaranteed.

PMID- 24327267
TI  - Healthcare use and costs associated with children's behavior problems.
AB  - The objective of the study was to investigate associations between severity of
      behavior problems, specific symptom domains with healthcare use and costs in
      school-aged children. A cross-sectional study using data from the 10-year follow
      up of two population-based birth cohorts was conducted on four rural and urban
      communities in Germany. There were 3,579 participants [1,834 boys (51%), 1,745
      girls (49%)] on average aged 10.4 years. The severity levels (normal, at risk,
      abnormal) and symptom domains of behavioral problems were assessed by parent
      reported strengths and difficulties questionnaire (SDQ).The outcomes were medical
      use categories (physicians, therapists, hospital, and rehabilitation), medical
      costs categories and total direct medical use and costs (calculated from parent
      reported utilization of healthcare services during the last 12 months). Total
      direct medical costs showed a graded relationship with severity level (adjusted p
      < 0.0001). Average annual cost difference in total direct medical costs between
      at risk and normal total difficulties was Euro (<euro>) 271 (SD 858), and <euro>
      1,237 (SD 2,528) between abnormal and normal total difficulties. A significant
      increase in physician costs showed between children with normal and at risk total
      difficulties (1.30), and between normal and abnormal total difficulties (1.29; p
      < 0.0001). Between specific symptom domains, children with emotional symptoms
      showed highest costs for physicians, psychotherapist, and hospitalization as well
      as total direct medical costs. Children with hyperactivity/inattention showed
      highest costs for therapists and emergency room costs. Healthcare use and costs
      are related to the severity of child behavior problems. In general, children's
      costs for psychotherapy treatments have been low relative to general medical
      treatments which may indicate that some children with behavioral problems did not
      get appropriate care. To some degree, medical conditions may be attributable to
      some of the high hospitalization costs found in children with emotional symptom.

PMID- 24327268
TI  - Hepatocyte-specific Ptpn6 deletion promotes hepatic lipid accretion, but reduces
      NAFLD in diet-induced obesity: potential role of PPARgamma.
AB  - Hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)) are protected from hepatic
      insulin resistance evoked by high-fat diet (HFD) feeding for 8 weeks.
      Unexpectedly, we report herein that Ptpn6(H-KO) mice fed an HFD for up to 16
      weeks are still protected from insulin resistance, but are more prone to hepatic
      steatosis, as compared with their HFD-fed Ptpn6(f/f) counterparts. The livers
      from HFD-fed Ptpn6(H-KO) mice displayed 1) augmented lipogenesis, marked by
      increased expression of several hepatic genes involved in fatty acid
      biosynthesis, 2) elevated postprandial fatty acid uptake, and 3) significantly
      reduced lipid export with enhanced degradation of apolipoprotein B (ApoB).
      Despite more extensive hepatic steatosis, the inflammatory profile of the HFD-fed
      Ptpn6(H-KO) liver was similar (8 weeks) or even improved (16 weeks) as compared
      to their HFD-fed Ptpn6(f/f) littermates, along with reduced hepatocellular damage
      as revealed by serum levels of hepatic enzymes. Interestingly, comparative
      microarray analysis revealed a significant up-regulation of peroxisome
      proliferator-activated receptor gamma (PPARgamma) gene expression, confirmed by
      quantitative polymerase chain reaction. Elevated PPARgamma nuclear activity also
      was observed and found to be directly regulated by Shp1 in a cell-autonomous
      manner. CONCLUSION: These findings highlight a novel role for hepatocyte Shp1 in
      the regulation of PPARgamma and hepatic lipid metabolism. Shp1 deficiency
      prevents the development of severe hepatic inflammation and hepatocellular damage
      in steatotic livers, presenting hepatocyte Shp1 as a potential novel mediator of
      nonalcoholic fatty liver diseases in obesity.

PMID- 24327269
TI  - Value-based differential pricing: efficient prices for drugs in a global context.
AB  - This paper analyzes pharmaceutical pricing between and within countries to
      achieve second-best static and dynamic efficiency. We distinguish countries with
      and without universal insurance, because insurance undermines patients' price
      sensitivity, potentially leading to prices above second-best efficient levels. In
      countries with universal insurance, if each payer unilaterally sets an
      incremental cost-effectiveness ratio (ICER) threshold based on its citizens'
      willingness-to-pay for health; manufacturers price to that ICER threshold; and
      payers limit reimbursement to patients for whom a drug is cost-effective at that
      price and ICER, then the resulting price levels and use within each country and
      price differentials across countries are roughly consistent with second-best
      static and dynamic efficiency. These value-based prices are expected to differ
      cross-nationally with per capita income and be broadly consistent with Ramsey
      optimal prices. Countries without comprehensive insurance avoid its distorting
      effects on prices but also lack financial protection and affordability for the
      poor. Improving pricing efficiency in these self-pay countries includes improving
      regulation and consumer information about product quality and enabling firms to
      price discriminate within and between countries.

PMID- 24327270
TI  - Clusterin is a gene-specific target of microRNA-21 in head and neck squamous cell
      carcinoma.
AB  - PURPOSE: MicroRNA-21 (miRNA-21) has proto-oncogenic properties, although no miRNA
      21-specific targets have been found in head and neck squamous cell carcinoma
      (HNSCC). Further study of miRNA-21 and its specific targets is essential to
      understanding HNSCC biology. EXPERIMENTAL DESIGN: miRNA expression profiles of 10
      HNSCCs and 10 normal mucosa samples were investigated using a custom miRNA
      microarray. Thirteen HNSCCs and five normal mucosa primary tissue specimens
      underwent mRNA expression microarray analysis. To identify miRNA-21 downstream
      targets, oral keratinocyte cells were subjected to microarray analysis after
      miRNA-21 transient transfection. miRNA and mRNA expression were validated by
      reverse transcription quantitative polymerase chain reaction (RT-qPCR) in a
      separate cohort of 16 HNSCCs and 15 normal mucosal samples. Microarray and
      bioinformatics analyses were integrated to identify potential gene targets. In
      vitro assays looked at the function and interaction of miRNA-21 and its specific
      gene targets. RESULTS: miRNA-21 was upregulated in HNSCCs and stimulated cell
      growth. Integrated analyses identified Clusterin (CLU) as a potential miRNA-21
      gene target. CLU was downregulated after forced expression of miRNA-21 in normal
      and HNSCC cell lines. The activity of a luciferase construct containing the 3'
      untranslated region (UTR) of CLU was repressed by the ectopic expression of miRNA
      21. CLU was also downregulated in primary HNSCCs and correlated with miRNA-21
      overexpression. CLU variant 1 (CLU-1) was the predominant splice variant in
      HNSCCs and showed growth suppression function that was reversed by miRNA-21
      overexpression. CONCLUSIONS: CLU is a specific, functional target of oncogenic
      miRNA-21 in HNSCCs. CLU-1 isoform is the predominant growth-suppressive variant
      targeted by miRNA-21.

PMID- 24327271
TI  - Aspirin and colorectal cancer: back to the future.
AB  - Abundant epidemiologic evidence indicates that regular and long-term use of
      aspirin is associated with a significant reduction in the incidence of colorectal
      cancer. The long duration of aspirin needed to prevent colorectal cancer is
      believed to be due to inhibition of precursor lesions known as adenomas, the
      recurrence of which is inhibited by aspirin in randomized trials. Aspirin intake
      has also been associated with a statistically significant improvement in patient
      survival after curative resection of colorectal cancer in large observational
      studies. In these cohorts, the survival benefit of aspirin was shown to depend
      upon the level of COX-2 expression in the primary colorectal cancer. More recent
      analysis of patient tumors from these observational cohorts suggests that the
      benefit of aspirin may be limited to specific molecular subtypes. Aspirin intake
      following colorectal cancer resection was associated with a significant
      improvement of survival in patients whose tumors carried mutant, but not wild
      type, copies of the phosphoinositide 3-kinase (PI3KCA) gene, especially tumors
      that overexpressed COX-2. A mechanistic explanation is suggested by the finding
      that inhibition of COX-mediated prostaglandin E2 synthesis by aspirin attenuates
      PI3K signaling activity that is known to regulate cancer cell proliferation and
      survival. Aspirin has also been shown to reduce the incidence of colorectal
      cancers bearing wild-type, but not mutant alleles of the BRAF(V600E) oncogene.
      Although provocative, the potential utility of these molecular markers for
      predicting aspirin efficacy awaits prospective evaluation in clinical trials. If
      validated, these findings may support a personalized approach to using aspirin
      for the therapy of colorectal cancer.

PMID- 24327272
TI  - Synergistic antitumor activity of cetuximab and namitecan in human squamous cell
      carcinoma models relies on cooperative inhibition of EGFR expression and depends
      on high EGFR gene copy number.
AB  - PURPOSE: Despite the frequent overexpression of epidermal growth factor receptor
      (EGFR) in squamous cell carcinoma (SCC), the efficacy of cetuximab alone is
      limited. Given the marked activity of namitecan, a hydrophilic camptothecin,
      against SCC models, the present study was performed to explore the efficacy of
      the cetuximab-namitecan combination in a panel of SCC models. EXPERIMENTAL
      DESIGN: We examined the antiproliferative and antitumor activities of the
      cetuximab-namitecan combination in four SCC models characterized by a different
      EGFR gene copy number/EGFR protein level. We also assessed the effects of the
      combination on EGFR expression at both mRNA and protein levels and investigated
      the molecular basis of the interaction between the two agents. RESULTS: Cetuximab
      and namitecan exhibited synergistic effects, resulting in potentiation of cell
      growth inhibition and, most importantly, enhanced therapeutic efficacy, with high
      cure rates in three SCC models characterized by high EGFR gene copy number,
      without increasing toxicity. The synergistic antitumor effect was also observed
      with the cetuximab-irinotecan combination. At the molecular level, the two agents
      produced a cooperative effect resulting in complete downregulation of EGFR.
      Interestingly, when singly administered, the camptothecin was able to strongly
      decrease EGFR expression mainly by transcriptional inhibition. CONCLUSIONS: Our
      results (i) demonstrate a marked efficacy of the cetuximab-namitecan combination,
      which reflects a complete abrogation of EGFR expression as a critical determinant
      of the therapeutic improvement, in SCC preclinical models, and (ii) suggest EGFR
      gene copy number as a possible marker to be used for patient selection in the
      clinical setting.

PMID- 24327274
TI  - microRNA-202-3p inhibits cell proliferation by targeting ADP-ribosylation factor
      like 5A in human colorectal carcinoma.
AB  - PURPOSE: MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have
      recently reshaped our understanding of the role of non-protein-coding RNAs. Here,
      we focused on the function and molecular mechanism of miR-202-3p and its
      potential clinical application in colorectal cancer. EXPERIMENTAL DESIGN: miR-202
      3p expression was determined by quantitative reverse transcriptase PCR (qRT-PCR)
      in 94 colorectal cancer tissues and corresponding noncancerous tissues (NCT).
      Cell proliferation and colony formation assays in vitro and xenograft experiments
      in vivo were used to evaluate the effect of miR-202-3p on colorectal cancer cell
      proliferation. Luciferase assay and Western blot analysis were performed to
      validate the potential targets of miR-202-3p after the preliminary screening by
      online prediction and microarray analysis. The mRNA and protein levels of target
      genes were detected by qRT-PCR and immunohistochemical staining. The copy number
      of pre-miR-202 was measured by quantitative PCR. RESULTS: First, miR-202-3p was
      significantly downregulated in 46.7% colorectal cancer samples compared with
      NCTs. The overexpression of miR-202-3p inhibited colorectal cancer cell growth in
      vitro and repressed tumorigenesis in nude mice. Then, miR-202-3p downregulated
      ADP-ribosylation factor-like 5A (ARL5A) protein level by binding to its 3'
      untranslated region, and knockdown of ARL5A phenocopied the proliferation
      inhibition effect of miR-202-3p. Furthermore, both of ARL5A mRNA and protein
      levels were upregulated in colorectal cancer samples compared with NCTs and high
      ARL5A protein levels predicted a poor prognosis. CONCLUSIONS: miR-202-3p might
      function as a tumor suppressor in colorectal cancer, and ARL5A, the functional
      target of miR-202-3p in colorectal cancer, is a potential prognostic factor for
      colorectal cancer.

PMID- 24327276
TI  - Are Classrooms Meeting the Basic Psychological Needs of Children With ADHD
      Symptoms? A Self-Determination Theory Perspective.

PMID- 24327275
TI  - Physicochemical properties and anti-Propionibacterium acnes activity of film
      forming solutions containing alpha-mangostin-rich extract.
AB  - The objective of this study was to study the effect of formulation compositions
      on physicochemical properties and anti-Propionibacterium acnes activity of film
      forming solutions containing alpha-mangostin-rich extract (AM). Film-forming
      solution bases and film-forming solutions containing AM were prepared by using
      Eudragit RL PO or Klucel LF or combinations of them as film-forming polymers.
      Rheological properties, pH values of the solutions, and mechanical properties of
      the dry films were investigated. An optimized formulation was selected and
      evaluated for the film surface, in vitro AM release, an anti-P. acnes activity,
      and potential for being a skin irritant. It was found that mechanical properties
      of the dry films were affected by total polymer contents, ratios of Klucel
      LF/Eudragit RL PO, AM, and contents of triethyl citrate. The film-forming
      solutions containing AM had pH values around 7.0. Their flow curves exhibited
      Newtonian flow behaviors. The optimized formulation provided films possessing
      smooth and nonporous surfaces. These films showed greater anti-P. acnes activity
      than their base films without toxicity to skin fibroblasts. Furthermore, AM
      released from the film matrix obeyed Higuchi's equation. In conclusion, the film
      forming solutions containing AM had potential for treatment of acne vulgaris
      caused by P. acnes. However, further in vivo study is necessary to determine
      their efficacy and safety for using in patients suffering from acne vulgaris. 

PMID- 24327273
TI  - Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK
      rearranged non-small cell lung cancer and predict strategies to overcome
      resistance.
AB  - PURPOSE: To extend the results of a phase III trial in patients with non-small
      cell lung cancer with adenocarcinomas harboring EML4-ALK fusion. EXPERIMENTAL
      DESIGN: We conducted a co-clinical trial in a mouse model comparing the ALK
      inhibitor crizotinib to the standard-of-care cytotoxic agents docetaxel or
      pemetrexed. RESULTS: Concordant with the clinical outcome in humans, crizotinib
      produced a substantially higher response rate compared with chemotherapy,
      associated with significantly longer progression-free survival. Overall survival
      was also prolonged in crizotinib- compared with chemotherapy-treated mice.
      Pemetrexed produced superior overall survival compared with docetaxel, suggesting
      that this agent may be the preferred chemotherapy in the ALK population. In
      addition, in the EML4-ALK-driven mouse lung adenocarcinoma model, HSP90
      inhibition can overcome both primary and acquired crizotinib resistance.
      Furthermore, HSP90 inhibition, as well as the second-generation ALK inhibitor
      TAE684, demonstrated activity in newly developed lung adenocarcinoma models
      driven by crizotinib-insensitive EML4-ALK L1196M or F1174L. CONCLUSIONS: Our
      findings suggest that crizotinib is superior to standard chemotherapy in ALK
      inhibitor-naive disease and support further clinical investigation of HSP90
      inhibitors and second-generation ALK inhibitors in tumors with primary or
      acquired crizotinib resistance.

PMID- 24327277
TI  - A Double Dissociation Between Inattentive and Impulsive Traits, on Tasks of
      Visual Processing and Emotion Regulation.
AB  - OBJECTIVE: To dissociate between inattentive and impulsive traits common in
      attention deficit hyperactivity disorder (ADHD) using a non-dichotomous
      measurment of these traits. METHOD: 120 university students who completed the
      Conner's adult ADHD rating scales (CAARS) were also tested on the Microgenesis
      task which requires visual attention and on the Cyber Cruiser task which requires
      emotion regulation. RESULTS: Results show that a measure of inattention was
      specifically related to a measure of effortful visual processing condition. In
      addition, a measure of impulsivity was specifically related to the tendency to
      fail in refueling one's car on time, although this relation was opposite to the
      predicted direction. Furthermore, by using exploratory and confirmatory factor
      analyses, the CAARS' factor structure was confirmed to be relevant to an Israeli
      population. CONCLUSION: The current experiment supports the idea that visual
      attention may play a part in inattentive symptoms, and that emotion regulation
      may play a part in impulsivity symptoms.

PMID- 24327278
TI  - Cannabis use: a perspective in relation to the proposed UK drug-driving
      legislation.
AB  - With regard to THC (Delta(9)-tetrahydrocannabinol), the main psychoactive
      constituent identified in the plant Cannabis sativa L, several facts are
      indisputable. Cannabis remains the most commonly used drug in the UK among those
      who reported driving under the influence of illegal drugs in the previous 12
      months. There is a significant dose-related decrement in driving performance
      following cannabis use; raised blood THC concentrations are significantly
      associated with increased traffic crash and death risk. When cannabis and alcohol
      are detected together, there is a greater risk to road safety than when either
      drug is used alone. Patterns of use are important when interpreting blood
      concentration data: Smoking infrequently a single cannabis cigarette leads to
      peak plasma THC concentrations (21-267 ug/L) causing acute intoxication. In
      habitual, daily users, plasma THC concentrations range from 1.0 to 11.0 ug/L and
      are maintained by sequestration of the drug from the tissues. These facts
      undoubtedly make setting thresholds for drug-driving legislation difficult but
      there is clearly a case for cannabis. Determining minimum blood THC
      concentrations at which a driver becomes sufficiently impaired to be unable to
      safely drive a vehicle is of particular concern given the increasing medicinal
      use of the drug. Internationally legislation for driving under the influence of
      drugs (DUID) is based on either a proof of impairment or a per se approach. For
      the latter this can be either zero-tolerance or based on concentration limits
      such as those used for alcohol. The different approaches are considered against
      current scientific evidence.

PMID- 24327279
TI  - [Highlights from yesterday's Clinical Monatsblatter Ophthalmology. 1899, Carlo
      Reymond].

PMID- 24327280
TI  - [Not Available].

PMID- 24327281
TI  - [Quantitative diagnostics].

PMID- 24327282
TI  - [Examination of visual performance by adaptive optics].
AB  - BACKGROUND: The dependence of visual quality on higher order aberrations (HOA) is
      highly important for refractive surgery (LASIK) as well as for the correction by
      vision aids. The use of the adaptive optics (AO) enables the measurement and
      manipulation of conventional lower order aberrations (defocus, astigmatism) and
      for HOAs as well. In this work, an Adaptive Optics Visual Simulator is presented
      that enables one to correct wave-front deformations up to the sixth order of
      Zernike polynomials, as well as to induce specific aberrations. The subjects
      observe a TFT monitor, so that a subjective rating of the visual impression is
      possible, as well as objective measurements. METHODS: Possible applications of
      such an adaptive optics visual simulator are demonstrated by means of several
      studies in this survey paper. The main challenge was to investigate the influence
      of HOAs on the subjective visual impression. Thereby, the following questions
      have been examined among others: Does the correction of the HOAs lead to an
      improved visual impression? Are there ways to check the effect of HOAs, what are
      the effects of single HOAs on the subjective visual impression and what just
      noticeable levels do they have? RESULTS: Three studies are presented
      investigating the impact of HOAs on visus, contrast sensitivity and on vision
      with glare as well as objective stimulus thresholds of selected HOAs. For
      example, by using a staircase-procedure it was possible to determine that the
      objective stimulus threshold for coma has a significantly lower value than the
      thresholds for astigmatism or trefoil. CONCLUSION: Adaptive optics enables the
      investigation of effects of HOAs on subjective and objective visual impression.
      In future, this may result in individualised corrections of refractive errors,
      which will improve the patient's quality of life.

PMID- 24327283
TI  - [Update on fs laser technology in ophthalmology].
AB  - Femtosecond (fs) lasers for LASIK flap creation have increased their market share
      from 0 percent in 2001 to over 55 percent in 2010. Now, in cataract surgery a
      similar revolution may take place. What makes this technology so special and
      which new areas of surgery will furthermore be entered in the future? This review
      elucidates the most important technical features of the fs lasers and interaction
      processes with the tissue. This understanding is intended to provide a better
      overview of the current market situation on the one hand. In addition, it can be
      estimated what kind of short- and long-term development this technology could
      take in the future. 

PMID- 24327284
TI  - [Comparison of dysphotopsia effects in phakic and pseudophakic eyes using Rostock
      glare perimeter].
AB  - BACKGROUND: Pseudophakic dysphotopsia as unwanted side effect after cataract
      surgery are becoming increasingly important. The so-called glare perimetry allows
      a realistic quantification of these phenomena. The article presents the method on
      the example of healthy subjects and pseudophakic patients. PATIENTS AND METHODS:
      Using glare perimetry phakic and pseudophakic subjects were examined for
      differences in disability glare. For this, data from 60 phakic persons of
      different ages (45 +/- 17.1 years) were used. As pseudophakic subjects 31
      carriers of monofocal lenses (70 +/- 6.7 years) and 25 carriers of multifocal
      lenses (71 +/- 8.5 years) were tested. RESULTS: Disability glare was
      significantly smaller in the phakic group (1.00 +/- 0.336 degrees ) than in the
      pseudophakic group (1.56 +/- 0.622 degrees ). Among the pseudophakic eyes those
      with a multifocal lens (1.69 +/- 0.367 degrees ) were significantly more
      sensitive to glare than those with a monofocal lens (1.43 +/- 0.492 degrees ).
      CONCLUSION: Glare perimetry allows an objective quantification of effects of
      dysphotopsia under realistic conditions. Pseudophakic eyes show a higher
      sensitivity to glare than eyes with the natural clear lens. Here, eyes with
      multifocal lenses prove to be particularly sensitive to glare.

PMID- 24327285
TI  - [Characterisation of tear film dynamics after application of trehalose for
      treatment of dry eye].
AB  - The implementation of additional modalities for tear film break-up time
      characterisation expands the application range of the Oculus(r) Keratograph 5M.
      The aim of the present study was to evaluate the possibilities for non-invasive
      break-up time analysis using this device. Furthermore we applied the Oculus(r)
      Keratograph 5M to characterise possible modifications of tear break-up time after
      application of Thealoz(r) eye drops (Thea Pharma). The device allowed for a
      precise and solid topographical analysis of tear film dynamics. We could show
      that at four weeks after treatment, trehalose solution was a better treatment for
      dry eye compared with saline. These results are in agreement with our previous in
      vitro findings concerning the protective role of trehalose on desiccation-caused
      cell death in a corneal epithelial model. 

PMID- 24327286
TI  - [Analysis and long-term observation after surgical treatment of patients with
      tumours of the iris].
AB  - BACKGROUND: Uveal melanoma is the most common primary intraocular malignancy in
      adults. Iris melanomas are rare tumours: they account for 2-3 % of all uveal
      melanomas. The clinical differentiation between benign iris nevi and malignant
      iris melanomas can be difficult. PATIENTS AND METHODS: The aim of this study was
      the registration, analysis and observation of all patients with tumours of the
      anterior uvea who had been treated surgically between 1992 and 2011 at the
      ophthalmic department of the University Hospital of Jena. 40 patients were
      analysed and compared concerning their preoperative states, operating methods
      including complications, histological results, postoperative function, subjective
      complaints as well as the risk of metastasis and the associated dependence on
      mortality of the dignity of the tumours. In this time period 26 patients has been
      observed in a follow-up visit. Patients with a malignant tumour were offered an
      examination. RESULTS: The histological examination revealed for 24 patients a
      benign tumour and for 16 patients a malignant tumour. After an exact analysis of
      multiple parameters there was only a statistically significant difference in the
      preoperative visual acuity (p = 0.025) and in the tumour size (p = 0.011) between
      the two analysed groups of patients. The rate of serious postoperative
      complications was 11.4 %. One fourth of the patients complained of subjective
      problems after the surgical intervention. In the follow-up visit a visual acuity
      of 0.5 or better was achieved in 68 % of all interventions. CONCLUSIONS: A
      reliable diagnosis is only possible after histological examination. The analysed
      parameters can only give indications for the dignity of the tumour. The strategy
      of the ophthalmic department of the University Hospital of Jena to remove a
      tumour of uncertain dignity at an early state makes sense, because there are few
      postoperative complications, few patients complain about subjective problems and
      the chances for achieving good visual acuity are high.

PMID- 24327287
TI  - [Ophthalmology lectures from the students' point of view].
AB  - INTRODUCTION: Lectures with many participants are considered inefficient and
      ophthalmology is seen as "not so important" for those studying medicine. We
      wondered about the students' view on this subject. METHODS: During the last
      lesson of a two-week-series of lectures together with the written test, 337
      students of two consecutive semesters received a questionnaire with specific
      questions concerning ophthalmology lectures. RESULTS: 257 questionnaires (76 %)
      were returned. The students claimed that the lecture itself contributed most of
      the knowledge for their later medical practice, more than books, scripts,
      internet etc. Interactivity was welcome, audience response systems were
      appreciated. Personal contact to the lecturers was considered less important, a
      variation of the lecturers was considered advantageous. It would be seen as a
      serious loss if the ophthalmology lecture were abolished. CONCLUSION: These
      results contradict clearly the concept of the unimportance of lectures with many
      participants and contradict as well tendencies not to teach "small" specialties
      in separate lectures.

PMID- 24327288
TI  - [Coping with wet age-related macular degeneration--a study from Switzerland].
AB  - BACKGROUND: Age-related macular degeneration (AMD) affects the quality of life of
      about 40,000 patients in Switzerland. The treatment of wet AMD with intravitreal
      injected anti-vascular endothelial growth factor (VEGF) can be a heavy burden for
      many patients. The aim of this study was to understand the quality of life of the
      patients and to seek ways to improve the treatment compliance. METHODS: Half
      structured telephone interviews with 28 patients between 56 and 94 years of age
      were transcribed and analysed. In 21 patients, both eyes were concerned with AMD.
      RESULTS: The quality of life of patients with AMD is reduced. Many activities of
      daily living are hindered. Dependence on others increases. Communication of the
      diagnosis is perceived as a shock. Most interviewees wish for more information
      about their specific situation. Auxiliary means and counselling possibilities are
      hardly known. CONCLUSION: Wet AMD impacts on the quality of life of the patient.
      Treatment should therefore not be limited to the medical treatment of the ill
      eye. Triage to rehabilitation and counselling services should be included as
      important duties of the medical practitioners.

PMID- 24327289
TI  - [Editorial on "The eye of an executed human"].

PMID- 24327290
TI  - [The eye of an executed human].

PMID- 24327291
TI  - [Obituary: Dr. Bernard Becker, Head of the Department of Ophthalmology and Visual
      Sciences of the Washington University Medical School, St. Louis, Missouri, 1953
      1988].

PMID- 24327293
TI  - Mouse divalent metal transporter 1 is a copper transporter in HEK293 cells.
AB  - Divalent Metal Transporter 1 (DMT1) is an apical Fe transporter in the duodenum
      and is involved in endosomal Fe export. Four protein isoforms have been described
      for DMT1, two from mRNA with an iron responsive element (IRE) and two from mRNA
      without it. The sets of two begin in exon 1A or 2. We have characterized copper
      transport using mouse 2/-IRE DMT1 during regulated ectopic expression. HEK293
      cells carrying a TetR:Hyg element were stably transfected with pDEST31 containing
      a 2/-IRE construct. (64)Cu(1+) incorporation in doxycycline treated cells
      exhibited 18.6 and 30.0-fold increases in Cu content, respectively when were
      exposed to 10 and 100 MUM of extracellular Cu. Cu content was ~4-fold above that
      of parent cells or cells carrying just the vector. (64)Cu uptake in transfected
      cells pre-incubated with 5 MUM of Cu-His revealed a Vmax and Km of 11.98 +/- 0.52
      pmol mg protein(-1) min(-1) and 2.03 +/- 0.03 MUM, respectively. Doxycycline
      stimulated Cu uptake was linear with time. The rates of apical Cu uptake
      decreased and transepithelial transport increased when intracellular Cu
      increased. The optimal pH for Cu transport was 6.5; uptake of Cu was temperature
      dependent. Silver does not inhibit Cu uptake in cells carrying the vector. In
      conclusion, Cu uptake in HEK293 cells that over-expressed the 2/-IRE isoform of
      DMT1 transporter supports our earlier contention that DMT1 transports Cu as
      Cu(1+). 

PMID- 24327292
TI  - Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with
      metastatic CEA-expressing carcinoma.
AB  - Yeast-CEA (GI-6207) is a therapeutic cancer vaccine genetically modified to
      express recombinant carcinoembryonic antigen (CEA) protein, using heat-killed
      yeast (Saccharomyces cerevisiae) as a vector. In preclinical studies, yeast-CEA
      induced a strong immune response to CEA and antitumor responses. Patients
      received subcutaneous vaccines every 2 weeks for 3 months and then monthly.
      Patients were enrolled at 3 sequential dose levels: 4, 16, and 40 yeast units
      (10(7) yeast particles/unit). Eligible patients were required to have serum CEA >
      5 ng/mL or > 20 % CEA(+) tumor block, ECOG PS 0-2, and no history of
      autoimmunity. Restaging scans were performed at 3 months and then bimonthly.
      Peripheral blood was collected for the analysis of immune response (e.g., by
      ELISPOT assay). Twenty-five patients with metastatic CEA-expressing carcinomas
      were enrolled. Median patient age was 52 (range 39-81). A total of 135 vaccines
      were administered. The vaccine was well tolerated, and the most common adverse
      event was grade 1/2 injection-site reaction. Five patients had stable disease
      beyond 3 months (range 3.5-18 months), and each had CEA stabilization while on
      study. Some patients showed evidence post-vaccination of increases in antigen
      specific CD8(+) T cells and CD4(+) T lymphocytes and decreases in regulatory T
      cells. Of note, a patient with medullary thyroid cancer had substantial T cell
      responses and a vigorous inflammatory reaction at sites of metastatic disease.
      Yeast-CEA vaccination had minimal toxicity and induced some antigen-specific T
      cell responses and CEA stabilization in a heterogeneous, heavily pre-treated
      patient population. Further studies are required to determine the clinical
      benefit of yeast-CEA vaccination.

PMID- 24327294
TI  - A model of glycosylated human butyrylcholinesterase.
AB  - Human butyrylcholinesterase (BChE) and its mutants have shown great potential in
      treating cocaine overdose and addiction. In order to effectively suppress cocaine
      reward in the brain for a long period of time after an exogenous cocaine
      hydrolase administration, the therapeutic enzyme should have not only a high
      catalytic efficiency against cocaine, but also a sufficiently long circulation
      time. It has been known that PEGylation (covalent attachment of polyethylene
      glycol) modification of a therapeutic protein can prolong the biological half
      life of the protein without affecting its biological function. However, the
      asparagine-linked glycans on the surface of glycosylated BChE may interfere with
      the PEGylation modification. In this study, we built a three-dimensional (3D)
      model of glycosylated human BChE to investigate the influence of glycans on the
      PEGylation modification. Glycans did not change the overall stability of the BChE
      structure, but could increase the flexibility of some local structures. For
      further evaluating the accessibility of the PEGylation reaction sites,
      particularly lysine residues, on the protein surface, we calculated the Solvent
      Accessible Surface Areas (SASAs) of these residues. The results indicate that
      some lysine residues show a significant decrease in SASA due to the direct or
      indirect influence of their surrounding glycans. The results also indicate that
      PEGylation reaction agents with smaller functional groups could have a better
      chance to react with lysine residues. This investigation provides a structural
      basis for rational engineering of human BChE and its mutants as therapeutic
      candidates. 

PMID- 24327295
TI  - Testing pathways linking exposure to community violence and sexual behaviors
      among African American youth.
AB  - Exposure to community violence and HIV sexual risks are two major public health
      concerns among youth. This study tests various pathways linking exposure to
      community violence and sexual behaviors among African American adolescents. Using
      a sample of 563 (61% females) African American youth attending high school we
      examined whether problematic psychological symptoms, low school engagement,
      and/or negative perceptions of peer norms about safer sex functioned as pathways
      linking exposure to community violence and sexual behaviors. Major findings
      indicated that, for boys, the relationship between exposure to community violence
      and sexual debut and sexual risk behaviors were linked by aggression. In
      addition, the relationship between exposure to community violence and sexual risk
      behaviors were linked by negative perceptions of peer attitudes about safer sex.
      For girls, the relationship between exposure to community violence and sexual
      debut was linked by aggression and negative perceptions of peer attitudes about
      safer sex. These findings provide support for pathways linking exposure to
      community violence to sexual behaviors.

PMID- 24327296
TI  - Age at menarche and adolescent alcohol use.
AB  - Research has shown that early maturation is related to problematic alcohol use,
      yet the differential effect of early pubertal timing (i.e., younger age at
      menarche) on the onset of alcohol use and subsequent level of alcohol use has
      rarely been examined. This distinction is relevant, as younger age at menarche
      can have differential effects on these outcomes, which in turn can have long
      lasting effects. Therefore, the present study examined the relationship between
      age at menarche and adolescent alcohol use among girls, hereby distinguishing
      between onset and level of alcohol use. In addition, the moderating effects of
      alcohol-specific rules, child disclosure and class gender composition were
      examined. Participants were 430 girls from a Dutch four-wave survey, with a mean
      age of 12.17 years (SD = 0.50) at the beginning of the study. Results showed that
      the probability of onset of alcohol use was increased by younger age at menarche,
      but only when girls were younger than 15. Moderation analyses showed that younger
      age at menarche increased the risk of alcohol onset only in low risk girls (with
      high levels of alcohol-specific rules and in classes with a high percentage of
      girls). Once adolescent girls started drinking alcohol, younger age at menarche
      was associated positively with alcohol consumption only for girls in classes with
      a moderate to high percentage of girls. These findings confirm that younger age
      at menarche is a risk factor for the onset of alcohol use, but strongly suggest
      that this effect is strongest for girls having restrictive alcohol-specific rules
      and in classes with a high percentage of girls. Possibly, in the absence of
      social factors that "push" to alcohol use, biological factors (like age at
      menarche) become more important. Another possibility is that adolescent girls
      start drinking alcohol to oppose their parents if they set too strict alcohol
      specific rules. 

PMID- 24327297
TI  - Opioids for chronic refractory breathlessness: right patient, right route?
AB  - Chronic breathlessness at rest or on minimal exertion despite optimal treatment
      of the underlying chronic cause(s) is termed chronic refractory breathlessness.
      This is prevalent across the community and is an independent indicator of poor
      prognosis. This narrative review focuses on the palliation of chronic refractory
      breathlessness in people predominantly with non-cancer diagnoses. Breathlessness
      is a complex sensation with at least three dimensions--intensity,
      distress/unpleasantness and its impact on function. It is the conscious
      representation of a mismatch between central ventilatory drive (the demand to
      breathe) and the responding respiratory output (the ability to breathe).
      Measurement relies on subjective reports by patients using a choice of uni- and
      multi-variable tools; the minimal clinically important difference is the smallest
      change conceived as clinically meaningful by the patients. Exogenous and
      endogenous opioids work centrally to reduce the sensation of breathlessness, with
      morphine as a mu opioid receptor agonist the most widely studied. Regular, low
      doses of sustained-release morphine have been shown to safely reduce
      breathlessness in this setting without evidence of respiratory depression nor
      obtundation. Patients should be initiated at a dosage of 10 mg/24 h and titrated
      by 10 mg if there is no benefit once in steady state. The highest dosage in the
      only dose-ranging study published to date was only 30 mg/24 h. Predictors of
      response to opioids for chronic refractory breathlessness include younger people
      with more severe breathlessness at baseline. Future research should address
      whether upward titration delivers further clinical benefit and whether all
      underlying aetiologies respond as predictably to opioids.

PMID- 24327298
TI  - New approaches to antiretroviral drug delivery: challenges and opportunities
      associated with the use of long-acting injectable agents.
AB  - Research on improved treatment of HIV infection and pre-exposure prophylaxis
      continues. Poor adherence to treatment is the critical risk factor for
      virological failure and resistance development, and long-acting formulations of
      anti-HIV medications that need only infrequent dosing may facilitate long-term
      therapeutic responses. Importantly, long-acting formulations of therapeutic
      agents have been used to avoid missing doses or treatment fatigue to prescribed
      lifelong medications in a number of different medical fields, with demonstrable
      success. However, such formulations are associated with challenges, such as the
      prolongation of adverse events with the persistence of drug concentrations and
      concerns over the development of resistance as a result of selective pressure as
      drug concentrations decline. Furthermore, long-acting injectable formulations of
      antiretroviral (ARV) agents with infrequent dosing may be advantageous over daily
      oral drug intake to prevent transmission of HIV. However, the knowledge on
      protective drug concentrations and frequency of dosing is poor to date and
      implementation globally is challenging. Importantly, if nanoformulations of ARVs
      requiring lower drug doses become available globally, the potential for treatment
      cost reductions is high, as, especially in resource-limited settings, the active
      pharmaceutical ingredient accounts for the greater proportion of the total cost
      of the medicine. In conclusion, different long-acting ARVs are being studied in
      phase I/II for both the treatment and prevention of HIV infection, and research
      on administering these agents in combination has started. 

PMID- 24327299
TI  - What do the data show? Knowledge map development for comprehensive environmental
      assessment.
AB  - Environmental and human health risk assessments benefit from using data that
      cross multiple scientific domains. Although individual data points may often be
      readily understood, the total picture can be difficult to envision. This is
      especially true with gaps in the data (e.g., with emerging substances such as
      engineered nanomaterials [ENM]), such that simply presenting only known
      information can result in a skewed picture. This study describes a method for
      building knowledge maps (KM) to visually summarize factors relevant to risk
      assessment in a relatively easy to interpret format. The KMs were created in the
      context of the comprehensive environmental assessment (CEA) approach for research
      planning and risk management of environmental contaminants. Recent applications
      of CEA to emerging substances such as engineered nanomaterials that have numerous
      data gaps have suggested that a more visually based depiction of information
      would improve the approach. We developed KM templates as a pilot project, to
      represent pertinent aspects of conceptual domains, and to highlight gaps in
      available information for one particular portion of a specific CEA application:
      the comparison of environmental transport, transformation, and fate of
      multiwalled carbon nanotubes (MWCNTs) and decabromodiphenyl ether as flame
      retardants. The results are 3 KM templates representing Physical Properties,
      Transport, and Transformation. The 3 templates were applied to both substances,
      resulting in a total of 6 KMs. In addition to presenting the KMs, this paper
      details the process used to generate them, to aid KM development for other
      sections of CEA applied to MWCNTs, or to apply the process to new CEA
      applications.

PMID- 24327300
TI  - [Post-surgical treatment after non-penetrating glaucoma surgery: the
      goniopuncture].
AB  - Non-penetrating glaucoma surgery was primarily developed as an alternative to the
      widely applied trabeculectomy. Since the anterior chamber in non-penetrating
      surgery is not directly opened, common postoperative complications such as
      hypotony are rare. The most frequently applied technique in this group is the
      deep sclerectomy. After having prepared a superficial scleral flap a deeper
      scleral flap is performed and excised unroofing Schlemm's canal. The trabecular
      meshwork is then peeled leaving a residual trabeculodescemet membrane. As a
      consequence aqueous humour diffuses via the trabeculodescemet membrane under the
      scleral flap and subsequently under the conjunctiva. One of the reasons for a
      postoperatively high IOP is seen in the resistance of the residual
      trabculodescemet membrane. A solution to this problem lies in its puncture, the
      so-called goniopuncture. Goniopunctures are done in approximately 50 % of cases
      after deep sclerectomy and are also applied in cases of canaloplasty and
      viscocanaloplasty. Usually a 1064 nm Nd : YAG laser is used. A potential risk of
      iris incarceration is described. Two studies have shown that an equally IOP
      lowering effect can be achieved by treating the trabeculodescemet membrane with a
      frequency-doubled 532 nm Nd : YAG laser (SLT). No complications were detected in
      those cases. In conclusion, goniopuncture should be considered as the first line
      treatment for postoperative IOP increase in cases of non-penetrating glaucoma
      surgery. It should therefore be preferred to a (re)start of topical treatment. 

PMID- 24327301
TI  - [Upper eyelid blepharoplasty with the CO2 laser].
AB  - Eyelid blepharoplasty is a common plastic surgical procedure in patients between
      the age of 40 and 60 and is performed by different specialists. Preoperative
      evaluation and understanding the patient's aesthetic expectations are essential
      for surgery planning. Laser blepharoplasty offers the possibility to perform
      incision and haemostasis with the same device. This article reports on our
      experience with the CO2 laser. 

PMID- 24327302
TI  - [Specific gene therapy for hereditary retinal dystrophies - an update].
AB  - Treatment possibilities based on specific gene therapy strategies have become
      reality for a small number of patients with hereditary retinal dystrophies and
      are currently under investigation in several clinical trials worldwide. The most
      advanced studies are for patients suffering from mutations in the RPE65 gene. In
      addition, studies are ongoing for patients with disease causing mutations in the
      MERTK, REP1, ABCA4, or Myosin7A gene. Depending on the size of the gene copy to
      be transferred, two vectors are currently used in clinical trials: vectors based
      on adeno-associated virus (AAV) or on lentivirus (equine infectious anaemia
      virus, EIAV). An important aspect of current research includes the capacity to
      objectively measure the treatment effect in patients, since this is currently
      limited. This article gives an overview of the current state of specific gene
      therapy for hereditary retinal dystrophies. 

PMID- 24327303
TI  - Facile preparation and characterization of BiOI-rectorite composite with high
      adsorptive capacity and photocatalytic activity.
AB  - Rectorite was composited with BiOI to extend its applicability as an applied
      material with high adsorptive capacity and photocatalytic activity. The facile
      synthesis process involved ultrasonic irradiation and in situ reaction. The
      physicochemical properties of the as-prepared samples were characterized by means
      of X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), X
      ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy
      (FESEM), transmission electron microscopy (TEM), N2 adsorption-desorption
      isotherms, and UV-vis diffuse reflectance spectroscopy (UV-vis DRS). Rhodamine B
      (RhB), a typical organic contaminant, was used as the model contaminant to
      evaluate the adsorption capacity and photocatalytic performance of the prepared
      BiOI-rectorite composite. The adsorption process was found to obey pseudo-second
      order kinetics. The equilibrium adsorption was well-modeled using the Freundlich
      adsorption isotherm. High photocatalytic activity under visible light irradiation
      was observed. 

PMID- 24327304
TI  - N-doped graphene derived from biomass as a visible-light photocatalyst for
      hydrogen generation from water/methanol mixtures.
AB  - There is much current interest in developing graphene-based materials as
      photocatalysts, particularly in the field of solar fuels and the photocatalytic
      generation of hydrogen. Graphene is a versatile material allowing different
      modification strategies to improve its activity. Thus, in the present manuscript
      we report that, in contrast to the lack of photocatalytic activity of undoped
      graphene, nitrogen doping introduces UV- and visible-light activity for hydrogen
      evolution; the efficiency of the material depends on the preparation conditions.
      The N-doped graphene is obtained by pyrolysis under an inert atmosphere of
      natural chitosan, which is considered a biomass waste, followed by ultrasound
      exfoliation, without the need of oxidation and reconstitution. The main parameter
      controlling the residual amount of nitrogen and the resulting photocatalytic
      activity is the pyrolysis temperature that produces an optimal material when the
      thermal treatment is carried out at 900  degrees C. Due to the fact that, in
      contrast to graphene oxide, N-doped graphene exhibits an almost "neutral"
      absorption spectrum, the material exhibits photocatalytic activity upon UV- (355
      nm) and visible-light (532 nm) irradiation, and is able to generate hydrogen upon
      simulated sunlight illumination.

PMID- 24327305
TI  - The expanded FindCore method for identification of a core atom set for assessment
      of protein structure prediction.
AB  - Maximizing the scientific impact of NMR-based structure determination requires
      robust and statistically sound methods for assessing the precision of NMR-derived
      structures. In particular, a method to define a core atom set for calculating
      superimpositions and validating structure predictions is critical to the use of
      NMR-derived structures as targets in the CASP competition. FindCore (Snyder and
      Montelione, Proteins 2005;59:673-686) is a superimposition independent method for
      identifying a core atom set and partitioning that set into domains. However, as
      FindCore optimizes superimposition by sensitively excluding not-well-defined
      atoms, the FindCore core may not comprise all atoms suitable for use in certain
      applications of NMR structures, including the CASP assessment process. Adapting
      the FindCore approach to assess predicted models against experimental NMR
      structures in CASP10 required modification of the FindCore method. This paper
      describes conventions and a standard protocol to calculate an "Expanded FindCore"
      atom set suitable for validation and application in biological and biophysical
      contexts. A key application of the Expanded FindCore method is to identify a core
      set of atoms in the experimental NMR structure for which it makes sense to
      validate predicted protein structure models. We demonstrate the application of
      this Expanded FindCore method in characterizing well-defined regions of 18 NMR
      derived CASP10 target structures. The Expanded FindCore protocol defines
      "expanded core atom sets" that match an expert's intuition of which parts of the
      structure are sufficiently well defined to use in assessing CASP model
      predictions. We also illustrate the impact of this analysis on the CASP GDT
      assessment scores.

PMID- 24327306
TI  - Tumor-associated macrophages are involved in tumor progression in papillary renal
      cell carcinoma.
AB  - Tumor-associated macrophages (TAMs) play a key role in cancer development.
      Especially, the immunosuppressive M2 phenotype is associated with increased tumor
      growth, invasiveness and metastasis. The differentiation of macrophages to the
      alternative phenotype M2 is mediated, inter alia, by macrophage colony
      stimulating factor (M-CSF). Papillary renal cell carcinoma (RCC) represents a
      rare tumor type which, based upon histological criteria, can be subdivided into
      two subtypes (I and II), of which type II is associated with poor prognosis. In
      both subtypes, typically, a dense infiltrate of macrophages is found. In the
      present study, the expression of CD68, CD163, M-CSF, Ki-67, and CD31 was examined
      in 30 type I and 30 type II papillary RCCs (n = 60). Both types of papillary RCCs
      contained an equally dense infiltrate of CD68-positive macrophages. Nearly all
      macrophages in papillary RCC type II expressed CD163, a characteristic for M2
      macrophages. In type I papillary RCC, less than 30 % of macrophages expressed
      CD163. Furthermore, tumor cells in type II papillary RCC expressed significantly
      more M-CSF and showed increased (Ki-67 expression defined) proliferative activity
      in comparison with type I papillary RCC. In addition, the (CD31 defined)
      capillary density was higher in type II than in type I papillary RCC. A dense
      infiltrate of M2 phenotype TAM and high M-CSF expression in tumor cells are key
      features of type II papillary RCC. These findings might explain why the prognosis
      of papillary RCC type II is worse than that of type I. 

PMID- 24327307
TI  - Characterization of UO2(2+) binding to osteopontin, a highly phosphorylated
      protein: insights into potential mechanisms of uranyl accumulation in bones.
AB  - Bones are one of the few organs in which uranyl (UO2(2+)) accumulates. This large
      dioxo-cation displays affinity for carboxylates, phenolates and phosphorylated
      functional groups in proteins. The noncollagenous protein osteopontin (OPN) plays
      an important role in bone homeostasis. It is mainly found in the extracellular
      matrix of mineralized tissues but also in body fluids such as milk, blood and
      urine. Furthermore, OPN is an intrinsically disordered protein, which, like other
      proteins of the SIBLING family, contains a polyaspartic acid sequence and
      numerous patterns of alternating acidic and phosphorylated residues. All these
      properties led to the hypothesis that this protein could be prone to UO2(2+)
      binding. In this work, a simple purification procedure enabling highly purified
      bovine (bOPN) and human OPN (hOPN) to be obtained was developed. Various
      biophysical approaches were set up to study the impact of phosphorylations on the
      affinity of OPN for UO2(2+) as well as the formation of stable complexes
      originating from structural changes induced by the binding of this metal cation.
      The results obtained suggest a new mechanism of the interaction of UO2(2+) with
      bone metabolism and a new role for OPN as a metal transporter. 

PMID- 24327308
TI  - Changing pattern of epidemiology in intrahepatic cholangiocarcinoma.

PMID- 24327310
TI  - Hospital discharge and the transition home for poor patients: "I knew I couldn't
      do what they were asking me".

PMID- 24327311
TI  - The mini mental status exam as a surrogate measure of health literacy.
AB  - BACKGROUND: Studies have documented strong associations between cognitive
      function, health literacy skills, and health outcomes, such that outcome
      performance may be partially explained by cognitive ability. Common cognitive
      assessments such as the Mini Mental Status Exam (MMSE) therefore may be measuring
      the same latent construct as existing health literacy tools. OBJECTIVES: We
      evaluated the potential of the MMSE as a surrogate measure of health literacy by
      comparing its convergent and predictive validity to the three most commonly used
      health literacy assessments and education. SUBJECTS: 827 older adults recruited
      from an academic general internal medicine ambulatory care clinic or one of five
      federally qualified health centers in Chicago, IL. Non-English speakers and those
      with severe cognitive impairment were excluded. MEASURES: Pearson correlations
      were completed to test the convergent validity of the MMSE with assessments of
      health literacy and education. Receiver Operating Characteristic (ROC) curves and
      the d statistic were calculated to determine the optimal cut point on the MMSE
      for classifying participants with limited health literacy. Multivariate logistic
      regression models were completed to measure the predictive validity of the new
      MMSE cut point. KEY RESULTS: The MMSE was found to have moderate to high
      convergent validity with the existing health literacy measures. The ROC and d
      statistic analyses suggested an optimal cut point of <= 27 on the MMSE. The new
      threshold score was found to predict health outcomes at least as well as, or
      better than, existing health literacy measures or education alone. CONCLUSIONS:
      The MMSE has considerable face validity as a health literacy measure that could
      be easily administered in the healthcare setting. Further research should aim to
      validate this cut point and examine the constructs being measured by the MMSE and
      other literacy assessments.

PMID- 24327312
TI  - An aqueous rechargeable battery based on zinc anode and Na(0.95)MnO2.
AB  - An aqueous rechargeable battery system is assembled by using metallic zinc and
      Na(0.95)MnO2 as the negative and positive electrodes, respectively. It is cheap
      and environmentally friendly, and its energy density is 78 Wh kg(-1). Its cycling
      performance is very good with only 8% capacity loss after 1000 cycles at 4 C
      between 1 and 2 V.

PMID- 24327309
TI  - Teamwork assessment in internal medicine: a systematic review of validity
      evidence and outcomes.
AB  - OBJECTIVE: Valid teamwork assessment is imperative to determine physician
      competency and optimize patient outcomes. We systematically reviewed published
      instruments assessing teamwork in undergraduate, graduate, and continuing medical
      education in general internal medicine and all medical subspecialties. DATA
      SOURCES: We searched MEDLINE, MEDLINE In-process, CINAHL and PsycINFO from
      January 1979 through October 2012, references of included articles, and abstracts
      from four professional meetings. Two content experts were queried for additional
      studies. STUDY ELIGIBILITY: Included studies described quantitative tools
      measuring teamwork among medical students, residents, fellows, and practicing
      physicians on single or multi-professional (interprofessional) teams. STUDY
      APPRAISAL AND SYNTHESIS METHODS: Instrument validity and study quality were
      extracted using established frameworks with existing validity evidence. Two
      authors independently abstracted 30 % of articles and agreement was calculated.
      RESULTS: Of 12,922 citations, 178 articles describing 73 unique teamwork
      assessment tools met inclusion criteria. Interrater agreement was intraclass
      correlation coefficient 0.73 (95 % CI 0.63-0.81). Studies involved practicing
      physicians (142, 80 %), residents/fellows (70, 39 %), and medical students (11, 6
      %). The majority (152, 85 %) assessed interprofessional teams. Studies were
      conducted in inpatient (77, 43 %), outpatient (42, 24 %), simulation (37, 21 %),
      and classroom (13, 7 %) settings. Validity evidence for the 73 tools included
      content (54, 74 %), internal structure (51, 70 %), relationships to other
      variables (25, 34 %), and response process (12, 16 %). Attitudes and opinions
      were the most frequently assessed outcomes. Relationships between teamwork scores
      and patient outcomes were directly examined for 13 (18 %) of tools. Scores from
      the Safety Attitudes Questionnaire and Team Climate Inventory have substantial
      validity evidence and have been associated with improved patient outcomes.
      LIMITATIONS: Review is limited to quantitative assessments of teamwork in
      internal medicine. CONCLUSIONS: There is strong validity evidence for several
      published tools assessing teamwork in internal medicine. However, few teamwork
      assessments have been directly linked to patient outcomes.

PMID- 24327313
TI  - Mirror therapy for phantom limb pain: brain changes and the role of body
      representation.
AB  - BACKGROUND: Phantom limb pain (PLP) is a common consequence of amputation and is
      difficult to treat. Mirror therapy (MT), a procedure utilizing the visual
      recreation of movement of a lost limb by moving the intact limb in front of a
      mirror, has been shown to be effective in reducing PLP. However, the neural
      correlates of this effect are not known. METHODS: We investigated the effects of
      daily mirror training over 4 weeks in 13 chronic PLP patients after unilateral
      arm amputation. Eleven participants performed hand and lip movements during a
      functional magnetic resonance imaging (fMRI) measurement before and after MT. The
      location of neural activity in primary somatosensory cortex during these tasks
      was used to assess brain changes related to treatment. RESULTS: The treatment
      caused a significant reduction of PLP (average decrease of 27%). Treatment
      effects were predicted by a telescopic distortion of the phantom, with those
      patients who experienced a telescope profiting less from treatment. fMRI data
      analyses revealed a relationship between change in pain after MT and a reversal
      of dysfunctional cortical reorganization in primary somatosensory cortex. Pain
      reduction after mirror training was also related to a decrease of activity in the
      inferior parietal cortex (IPC). CONCLUSIONS: Experienced body appearance seems to
      be an important predictor of mirror treatment effectiveness. Maladaptive changes
      in cortical organization are reversed during mirror treatment, which also alters
      activity in the IPC, a region involved in painful perceptions and in the
      perceived relatedness to an observed limb.

PMID- 24327314
TI  - Magnetic source localization of early visual mismatch response.
AB  - Previous studies have reported a visual analogue of the auditory mismatch
      negativity (MMN) response that is based on sensory memory. The neural generators
      and attention dependence of the visual MMN (vMMN) still remain unclear. We used
      magnetoencephalography (MEG) and spatio-temporal source localization to determine
      the generators of the sensory-memory-based vMMN response to non-attended
      deviants. Ten participants were asked to discriminate between odd and even digits
      presented at the center of the visual field while grating patterns with different
      spatial frequencies were presented outside the focus of attention. vMMN was
      calculated as the difference between MEG responses to infrequent gratings in
      oddball blocks and the same gratings in equiprobable blocks. The peak latency of
      the vMMN response was between 100 and 160 ms. The neuromagnetic sources of the
      vMMN localized in the occipital cortex differed from the sources evoked by the
      equiprobable gratings and were stimulus-dependent. Our results suggest the
      existence of separate neural systems for pre-attentive memory-based detection of
      visual change and provide new evidence that the vMMN is feature-specific.

PMID- 24327316
TI  - Approches medicales de la vulnerabilite humaine, or medical approaches to human
      vulnerability. Introduction.

PMID- 24327315
TI  - Reversing multidrug-resistant by RNA interference through silencing MDR1 gene in
      human hepatocellular carcinoma cells subline Bel-7402/ADM.
AB  - Multidrug resistance (MDR) in hepatocellular carcinoma (HC) significantly impedes
      the effect of chemotherapy and is considered as a primary reason leading to its
      recurrences and metastasis. The aim of present study was to explore new molecular
      targets for the reversal of MDR in HC by screening the adriamycin (ADM)-induced,
      human MDR-resistant HC cell subline Bel-7402/ADM. Small interfering RNAs (siRNAs)
      of four (MDR1si326, MDR1si1513, MDR1si2631 and MDR1si3071) targeting MDR1 were
      designed and transfected into Bel-7402/ADM cell strains. The experiments involved
      the following: mRNA expression of MDR1 gene by RT-PCR, P-glycoprotein (P-gp)
      expression by Western blot, intracellular ADM accumulation flow cytometry, and
      IC50 of ADM by a cytotoxic MTT assay. Four siRNAs reversed MDR in HC mediated by
      MDR1 to varying degrees. The expression level of MDR1 mRNA in cells of MDR1si326
      or MDR1si2631 group (0.190 +/- 0.038 or 0.171 +/- 0.011) was more decreased. The
      expression level of P-gp in cells of MDR1si326 group was the lowest. The
      accumulation of ADM in cells of MDR1si326 or MDR1si2631 group (77.0 +/- 3.5 or
      75.4 +/- 2.9) was more increased. The IC50 of cells to ADM was lowest in
      MDR1si326 group (11.32 +/- 0.69 mg/L). Compared with other three siRNAs,
      MDR1si326 performed the optimal reversal effect of drug resistance in human HC
      Bel-7402/ADM.

PMID- 24327317
TI  - Contribution of testosterone to the clock system in rat prostate mesenchyme
      cells.
AB  - Circadian rhythms are modulated in a variety of peripheral tissues including the
      prostate, in which the mesenchyme and epithelium cells are controlled under
      androgens. Here, we investigated the testosterone regulation of core clock genes
      such as Bmal1, Clock, Per2 and Nr1d1 under a deficient state of testosterone. In
      vivo studies showed that the Bmal1 mRNA expression in the prostates displayed a
      peak at ZT 20 and a trough at ZT 12. Both Bmal1 and Clock transcripts decreased
      after castration. Conversely, the expression of Per2 that is promoted by binding
      of Bmal1 and Clock heterodimers to the E-box, enhanced or did not decease at
      least within 1 week after castration. The clock gene transcripts were recovered
      to the intact levels, when 1 mg testosterone was administered daily for 5 days.
      Fluorescent immunohistochemical studies revealed the increased staining of
      caspase 3 in the epithelium and Per2 in both the mesenchyme and epithelium after
      1-week castration. In the mesenchyme cells prepared from castrated rats, the Per2
      oscillation was generated in response to dexamethasone. The circadian rhythms of
      Bmal1 and Nr1d1 transcripts were obviously antiphase in the cells. However, the
      mesenchyme cells displayed the different profiles in the presence or absence of
      testosterone; the amplitude of the first phase was significantly decreased by
      testosterone. Addition of testosterone significantly increased the transcripts of
      Bmal1, Clock and Casp3 in cultured cells, whereas the Per2 and Nr1d1 transcripts
      were significantly inhibited. Collectively, the present results demonstrated that
      Bmal1 and Clock, but not Per2 and Nr1d1, are down-regulated in mesenchyme cells
      by testosterone deficiency. In addition to the conservative interlocked
      transcriptional-translational feedback loop, it is strongly suggested that the
      prostate clock system is controlled under androgen.

PMID- 24327318
TI  - Multicolor detection of rare tumor cells in blood using a novel flow cytometry
      based system.
AB  - The presence and number of circulating tumor cells (CTCs) in the blood of
      patients with solid tumors are predictive of their clinical outcomes. To date,
      the CellSearch system is the only US Food and Drug Administration-approved CTC
      enumeration system for advanced breast, prostate, and colon cancers. However,
      sensitivity issues due to epithelial cellular adhesion molecule (EpCAM)-based
      enrichment and limited capability for subsequent molecular analysis must be
      addressed before CTCs can be used as predictive markers in the clinical setting.
      We have developed a multicolor CTC detection system using cross-contamination
      free flow cytometry, which permits the enumeration and characterization of CTCs
      for multiple molecular analyses. Tumor cell lines with different expression
      levels of EpCAM were spiked into peripheral blood obtained from healthy donors.
      Spike-in samples were negatively enriched using anti-CD45-coated magnetic beads
      to remove white blood cells, and this was followed by fixation and labeling with
      CD45-Alexa Fluor 700, EpCAM-phycoerythrin, cytokeratin (CK)-fluorescein
      isothiocyanate antibodies, and/or 7-aminoactinomycin D for nuclei staining.
      Excellent detection (slope = 0.760-0.888) and a linear performance (R(2) = 0.994
      0.998) were noted between the observed and expected numbers of tumor cells,
      independent of EpCAM expression. The detection rate was markedly higher than that
      obtained using the CellSearch system, suggesting the superior sensitivity of our
      system in detecting EpCAM- tumor cells. Additionally, the incorporation of an
      epithelial-mesenchymal transition (EMT) marker allowed us to detect EpCAM-/CK-
      cells and EMT-induced tumor cells. Taken together, our multicolor CTC detection
      system may be highly efficient in detecting previously unrecognized populations
      of CTCs.

PMID- 24327320
TI  - Decreased expression of Gab2 in patients with temporal lobe epilepsy and
      pilocarpine-induced rat model.
AB  - Growth factor receptor bound protein-2 associated binding protein-2 (Gab2) is
      widely expressed in the central nervous system, and participates in multiple
      signaling pathways. Recent studies showed that Gab2 was involved in the
      pathogenesis of Alzheimer's disease (AD). Gab2 reduces tau phosphorylation levels
      and is associated with cellular apoptosis and differentiation. However, whether
      Gab2 was also involved in the pathogenesis of epilepsy, remains unknown. This
      study aimed to investigate the expression pattern of Gab2 protein in brains with
      temporal lobe epilepsy (TLE) and in pilocarpine-induced rat model of TLE. Western
      blot, immunohistochemistry, and immunofluorescence were used to assess the
      location and the expression level of Gab2 in the neocortex of the temporal lobe
      in patients with TLE and in rat model of epilepsy. Results showed that Gab2
      protein was expressed mainly in the membranes and cytoplasm of neurons in the
      cortex and hippocampus. Gab2 protein expression was remarkably reduced in
      temporal neocortex of TLE patients. In hippocampus and adjacent cortex in rat
      epilepsy model, Gab2 expression was decreased at different time points after
      kindling compared with the controls, and the lowest level of Gab2 expression
      occurred at 1 week. Thus, significant reductions of Gab2 protein in both TLE
      patients and epilepsy rats suggest that Gab2 may play an important role in the
      pathogenesis of TLE.

PMID- 24327321
TI  - Rare combination of myasthenia and motor neuronopathy, responsive to Msc-Ntf stem
      cell therapy.

PMID- 24327323
TI  - A general method for N-methylation of amines and nitro compounds with
      dimethylsulfoxide.
AB  - DMSO methylates a broad range of amines in the presence of formic acid, providing
      a novel, green and practical method for amine methylation. The protocol also
      allows the one-pot transformation of aromatic nitro compounds into dimethylated
      amines in the presence of a simple iron catalyst. 

PMID- 24327325
TI  - Response profiles of cytokines and chemokines against avian H9N2 influenza virus
      within the mouse lung.
AB  - The circulation of H9N2 viruses throughout the world, along with their expanded
      host range, poses a potential health risk to the public, but the host responses
      to H9N2 virus in mammals were little known. To obtain insight into the host
      immune responses to the avian H9N2 virus, the expressions of both cytokines and
      chemokines in the lungs of infected mice were examined by real-time polymerase
      chain reaction and enzyme-linked immunosorbent assay. We found that interferon
      gamma (IFN-gamma) was the dominant antiviral component, and IFN-gamma-induced
      protein 10 kDa, interleukin 6, chemokine (C-C motif) ligand 5 and macrophage
      inflammatory protein-1 alpha all played a role in pro-inflammatory responses to
      H9N2 viruses. In conclusion, this research can make us further understand the
      infection characteristics of H9N2 virus in mammalian host by providing the data
      on mice lung immune responses to the avian H9N2 virus. 

PMID- 24327326
TI  - Risk factors for first time incidence sciatica: a systematic review.
AB  - BACKGROUND AND PURPOSE: Characteristically, sciatica involves radiating leg pain
      that follows a dermatomal pattern along the distribution of the sciatic nerve. To
      our knowledge, there are no studies that have investigated risk factors
      associated with first time incidence sciatica. The purpose of the systematic
      review was to identify the longitudinal risk factors associated with first time
      incidence sciatica and to report incidence rates for the condition. For the
      purposes of this review, first time incidence sciatica was defined as either of
      the following: 1) no prior history of sciatica or 2) transition from a pain-free
      state to sciatica. Studies included subjects of any age from longitudinal,
      observational, cohort designs. METHODS: The study was a systematic review. Eight
      of the 239 articles identified by electronic search strategies met the inclusion
      criteria. RESULTS: Risk factors and their respective effect estimates were
      reported using descriptive analysis and the preferred reporting items for
      systematic reviews and meta-analyses guidelines. Modifiable risk factors included
      smoking, obesity, occupational factors and health status. Non-modifiable factors
      included age, gender and social class. Incidence rates varied among the included
      studies, in part reflecting the variability in the operationalized definition of
      sciatica but ranged from <1% to 37%. DISCUSSION: A majority of the identified
      risk factors associated with first time sciatica are modifiable, suggesting the
      potential benefits of primary prevention. In addition, those risk factors are
      also associated with unhealthy lifestyles, which may function concomitantly
      toward the development of sciatica. Sciatica as a diagnosis is inconsistently
      defined among studies.

PMID- 24327327
TI  - Neuroimaging biomarkers and cognitive function in non-CNS cancer and its
      treatment: current status and recommendations for future research.
AB  - Cognitive changes in patients undergoing treatment for non-central nervous system
      (CNS) cancers have been recognized for several decades, yet the underlying
      mechanisms are not well understood. Structural, functional and molecular
      neuroimaging has the potential to help clarify the neural bases of these
      cognitive abnormalities. Structural magnetic resonance imaging (MRI), functional
      MRI (fMRI), diffusion tensor imaging (DTI), MR spectroscopy (MRS), and positron
      emission tomography (PET) have all been employed in the study of cognitive
      effects of cancer treatment, with most studies focusing on breast cancer and
      changes thought to be induced by chemotherapy. Articles in this special issue of
      Brain Imaging and Behavior are devoted to neuroimaging studies of cognitive
      changes in patients with non-CNS cancer and include comprehensive critical
      reviews and novel research findings. The broad conclusions that can be drawn from
      past studies and the present body of new research is that there are structural
      and functional changes associated with cancer and various treatments,
      particularly systemic cytotoxic chemotherapy, although some cognitive and fMRI
      studies have identified changes at pre-treatment baseline. Recommendations to
      accelerate progress include well-powered multicenter neuroimaging studies, a
      better standardized definition of the cognitive phenotype and extension to other
      cancers. A systems biology framework incorporating multimodality neuroimaging,
      genetics and other biomarkers will be highly informative regarding individual
      differences in risk and protective factors and disease- and treatment-related
      mechanisms. Studies of interventions targeting cognitive changes are also needed.
      These next steps are expected to identify novel protective strategies and
      facilitate a more personalized medicine for cancer patients. 

PMID- 24327328
TI  - Splenic vein thrombosis and pancreatic fistula after minimally invasive distal
      pancreatectomy.
AB  - BACKGROUND: This study aimed to investigate the clinical relevance of splenic
      vein thrombosis (SVT) in the splenic vein remnant following minimally invasive
      distal pancreatosplenectomy (DPS). METHODS: Medical records of patients who
      underwent laparoscopic or robotic distal pancreatectomy (DP) with or without
      splenectomy between January 2006 and August 2012 were reviewed. Rates of SVT and
      clinically relevant postoperative pancreatic fistula (POPF) were compared in a
      group of patients undergoing DPS and a group having spleen-preserving DP.
      RESULTS: Seventy-nine patients had minimally invasive DP, of whom 38 (48 per
      cent) developed SVT in the splenic vein remnant. DPS was associated with POPF (P
      = 0.001) and SVT (P < 0.001). SVT length was closely related to the amount of
      peripancreatic fluid collection (P = 0.025) and POPF (P = 0.045). In a comparison
      of splenic vessel-sacrificing, spleen-preserving DP and DPS, postoperative
      platelet count was significantly higher in the DPS group (P < 0.001). In
      addition, grade of SVT (P = 0.092) and POPF (P = 0.065) tended to be associated
      with DPS, suggesting that SVT may be related to both splenectomy and POPF.
      CONCLUSION: Minimally invasive DPS is associated with SVT and POPF. Preservation
      of the spleen should be considered when treating patients with benign and
      borderline malignant tumours of the distal pancreas.

PMID- 24327330
TI  - Regulation of acrosome reaction by Liprin alpha3, LAR and its ligands in mouse
      spermatozoa.
AB  - Zona pellucida-based induction of acrosome reaction (AR) is a popular and well
      accepted hypothesis. However, this hypothesis is being challenged in recent years
      and it has been proposed that the cumulus cells might be the site of AR. In our
      previous study, we reported the presence of a synaptic protein Liprin alpha3 on
      sperm acrosome, and proposed its role in AR. This study was designed to
      understand the role of Liprin alpha3 and its interacting proteins in regulation
      of AR. It is observed that the presence of anti-Liprin alpha3 antibody inhibits
      the process of AR. Colocalization experiments demonstrate the coexistence of
      leucocyte antigen related (LAR) protein, Rab-interacting molecule (RIM) and
      Liprin alpha3 on sperm acrosome thereby completing the identification of all the
      members of RIM/MUNC/Rab3A/liprinalpha complex required for membrane fusion. This
      study demonstrates the effect of LAR ligands such as Syndecans, Nidogens and LAR
      wedge domain peptide on AR. We could see an increase in AR in presence of these
      ligands. On the basis of these data, we speculate that in presence of ligands or
      wedge peptide, LAR undergoes dimerization leading to inhibition of phosphatase
      activity and increase in AR. The presence of one of the ligands Syndecan-1 on
      cumulus cells led us to hypothesize that it is Syndecan which induces AR in vivo
      and thus another site of AR could lie in cumulus. 

PMID- 24327331
TI  - Breast cancer screening of women aged 70-74 years: results from a natural
      experiment across Australia.
AB  - There is a lack of evidence regarding the optimal age at which to cease
      mammographic screening for breast cancer. This ecological study compared
      Australian state and territory level screening participation rates and cancer
      outcomes from 1996 to 2005 to identify the extent to which screening women aged
      70-74 results in smaller, earlier stage breast cancers. With each 10 % absolute
      increase in screening participation, there was no significant difference in
      cancer incidence, but the incidence of large cancers was 8 % lower (IRR = 0.92,
      95 % CI 0.90-0.94, p < 0.001); there was some evidence of reduced nodal
      involvement at diagnosis (IRR 0.97, 95 % CI 0.95-0.99, p = 0.004) but this
      estimate was sensitive to assumptions regarding missing data. Increased
      mammographic screening of women aged 70-74 years reduces the incidence of large
      (>15 mm) cancers-and possibly cancers with nodal involvement-without a
      concomitant increase in overall cancer incidence.

PMID- 24327329
TI  - Targeting inflammation: impact on atherothrombosis.
AB  - Atherothrombosis is a worldwide epidemic accounting for an unacceptable toll of
      deaths and disabilities. Its pathophysiology is complex and hardly referable to a
      specific mechanism; however, in the last 20 years, a growing amount of evidence
      has demonstrated that inflammatory processes play a major role from the very
      beginning to the ultimate complication of atherothrombosis. These evidences are
      addressing a growing interest toward anti-inflammatory agents as preventive or
      curative treatments of atherothrombosis. At present, accumulated data are not
      conclusive, but strong evidence exists in favor of an anti-inflammatory positive
      effect for several drugs as statins or renin-angiotensin inhibitors. More
      conclusive data are expected from ongoing trials directly exploring the role of
      specific cytokines antagonists. 

PMID- 24327332
TI  - Osteolysis and pain due to experimental bone metastases are improved by treatment
      with rapamycin.
AB  - In advanced breast cancer, bone metastases occur in 70 % of patients. Managing
      the devastating pain associated with the disease is difficult. Rapamycin is an
      immunomodulatory drug that targets the mammalian target of rapamycin pathway.
      Rapamycin has been shown to decrease osteolysis associated with metastatic breast
      cancer in pre-clinical models and to reduce pain in inflammatory and neuropathic
      models. The aim of this study was to evaluate the effectiveness of rapamycin in
      reducing pain associated with experimental osteolytic metastases. Bone cancer was
      induced by intra-tibial injections of murine mammary carcinoma cells (4T1) in
      immunocompetent BALB/c mice and treated intraperitoneally for up to 5 weeks with
      vehicle, rapamycin or pamidronate (a bisphosphonate currently used to reduce bone
      loss in bone cancer patients). The control group received intra-tibial injection
      with saline (sham) and was treated with vehicle intraperitoneally. Cancer-induced
      osteolysis was observed histologically and radiographically 2-3 weeks following
      cancer inoculation and gradually increased with time. Measures of evoked
      nociceptive behaviors including sensitivity to mechanical, thermal, and cold
      stimuli and spontaneous nociceptive behaviors (limping, guarding) were evaluated.
      Significant hypersensitivity to sensory stimuli developed in cancer-bearing mice
      compared to sham 3 weeks following inoculation. Rapamycin decreased or delayed
      the development of cancer-induced mechanical, heat, and cold hypersensitivity,
      while pamidronate reduced heat and cold hypersensitivity. Both rapamycin and
      pamidronate had a partial protective effect on the spontaneous nociceptive
      behaviors, limping and guarding. Our data suggest that rapamycin may have
      efficacy in the management of pain associated with metastatic breast cancer.

PMID- 24327333
TI  - Sixteen years follow-up results of a randomized phase II trial of neoadjuvant
      fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with
      cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast
      cancer: GOCS experience.
AB  - Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's
      sensitivity to therapy, eradication of micrometastatic disease and the
      possibility of performing breast conserving surgery. The aim of this study was to
      describe long-term results of NAC in stage III breast cancer patients. We
      evaluated 126 patients that participated in a phase II randomized trial of
      neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles
      prior to definitive surgery and radiotherapy, and then for six cycles as
      adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response
      rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There
      were no differences in median disease free survival (DFS) or overall survival
      (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After
      16 years of follow-up, 53 patients are still alive. Multivariate analysis showed
      that the number of pathologically involved lymph nodes (pLN) was the only factor
      associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both
      regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia,
      thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the
      best of our knowledge, this is the first study to report long-term outcomes of
      FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both
      regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years.
      After 5 years, the hazard of death seems to decline. The prolonged follow-up of
      this study provides a unique opportunity to evaluate factors that predict long
      term outcomes. After 16 years of follow-up, the number of pLN remains the most
      powerful predictor of survival. 

PMID- 24327334
TI  - A phase II study of combined fulvestrant and everolimus in patients with
      metastatic estrogen receptor (ER)-positive breast cancer after aromatase
      inhibitor (AI) failure.
AB  - Fulvestrant, which degrades ER, is used after AI failure in metastatic breast
      cancer but resistance develops quickly. We hypothesized that using everolimus to
      inhibit mTOR, a key signaling pathway in endocrine resistance, may delay
      fulvestrant resistance in patients and thus improve its efficacy. We conducted a
      phase II trial of combined fulvestrant and everolimus in postmenopausal women
      with disease progression or relapse after an AI. Primary endpoint was time to
      progression (TTP) and secondary endpoints included objective response rate,
      clinical benefit rate (CBR), safety, and biomarker correlates. Tumor blocks were
      collected and biopsy of accessible tumor was done for future biomarker analysis.
      Of 33 patients enrolled two were ruled ineligible after enrollment and were
      excluded from study analysis, for a total of 31 evaluable patients. Median age
      was 54 years (range 45-85). Prior therapy included tamoxifen (81 %), chemotherapy
      (71 %), with 26 % of patients having received 3 or more endocrine agents. Median
      TTP was 7.4 months (95 % CI 1.9-12.1) with an objective response rate of 13 % and
      CBR of 49 %. Of particular note, 32 % of patients exhibited de novo resistance to
      study treatment with disease progression as their best response. Most common
      adverse events (AEs) were elevated AST (87 %) and ALT (77 %), anemia (74 %),
      hyperglycemia (71 %), and hypercholesterolemia (68 %). Prominent clinical
      toxicities were mucositis (58 %), weight loss (48 %), and rash (42 %). Most AEs
      were grade 1 or 2 and largely reversible with infrequent need for everolimus dose
      reduction. To conclude, everolimus plus fulvestrant is effective after AI failure
      in heavily pretreated metastatic ER-positive breast cancer and has manageable
      toxicity. Further study of this combination is warranted in randomized studies.
      Since not all patients experience benefit, and in view of potential toxicities,
      biomarker examination is critical to help select patients most likely to benefit
      from this strategy in future studies. 

PMID- 24327335
TI  - Copy number variants are produced in response to low-dose ionizing radiation in
      cultured cells.
AB  - Despite their importance to human genetic variation and disease, little is known
      about the molecular mechanisms and environmental risk factors that impact copy
      number variant (CNV) formation. While it is clear that replication stress can
      lead to de novo CNVs, for example, following treatment of cultured mammalian
      cells with aphidicolin (APH) and hydroxyurea (HU), the effect of different types
      of mutagens on CNV induction is unknown. Here we report that ionizing radiation
      (IR) in the range of 1.5-3.0 Gy effectively induces de novo CNV mutations in
      cultured normal human fibroblasts. These IR-induced CNVs are found throughout the
      genome, with the same hotspot regions seen after APH- and HU-induced replication
      stress. IR produces duplications at a higher frequency relative to deletions than
      do APH and HU. At most hotspots, these duplications are physically shifted from
      the regions typically deleted after APH or HU, suggesting different pathways
      involved in their formation. CNV breakpoint junctions from irradiated samples are
      characterized by microhomology, blunt ends, and insertions like those seen in
      spontaneous and APH/HU-induced CNVs and most nonrecurrent CNVs in vivo. The
      similarity to APH/HU-induced CNVs suggests that low-dose IR induces CNVs through
      a replication-dependent mechanism, as opposed to replication-independent repair
      of DSBs. Consistent with this mechanism, a lower yield of CNVs was observed when
      cells were held for 48 hr before replating after irradiation. These results
      predict that any environmental DNA damaging agent that impairs replication is
      capable of creating CNVs.

PMID- 24327336
TI  - Mutation in FAM134B causing hereditary sensory neuropathy with spasticity in a
      Turkish family.

PMID- 24327337
TI  - The RNA/DNA-binding protein PSF relocates to cell membrane and contributes cells'
      sensitivity to antitumor drug, doxorubicin.
AB  - Cell surface proteins play an important role in multidrug resistance (MDR).
      However, the identification involving chemoresistant features for cell surface
      proteins is a challenge. To identify potential cell membrane markers in
      hematologic cancer MDR, we used a cell- and antibody-based strategy of
      subtractive immunization coupled with cell surface comparative screening of
      leukemia cell lines from sensitive HL60 and resistant HL60/DOX cells. Fifty one
      antibodies that recognized the cell surface proteins expressed differently
      between the two cell lines were generated. One of them, the McAb-5D12 not only
      recognizes its antigen but also block its function. Comparative analysis of
      immunofluorescence, flow cytometry, and mass spectrum analysis validated that the
      membrane antigen of McAb-5D12 is a nucleoprotein-polypyrimidine tract binding
      protein associated splicing factor, PSF. Our results identified that PSF
      overexpressed on the membrane of sensitive cells compared with resistant cells
      and its relocation from the nuclear to the cell surface was common in
      hematological malignancy cell lines and marrow of leukemia patients. Furthermore,
      we found that cell surface PSF contributed to cell sensitivity by inhibiting cell
      proliferation. The results represent a novel and potentially useful biomarker for
      MDR prediction. The strategy enables the correlation of expression levels and
      functions of cell surface protein with some cell-drug response traits by using
      antibodies.

PMID- 24327338
TI  - Segmenting patients and physicians using preferences from discrete choice
      experiments.
AB  - People often form groups or segments that have similar interests and needs and
      seek similar benefits from health providers. Health organizations need to
      understand whether the same health treatments, prevention programs, services, and
      products should be applied to everyone in the relevant population or whether
      different treatments need to be provided to each of several segments that are
      relatively homogeneous internally but heterogeneous among segments. Our objective
      was to explain the purposes, benefits, and methods of segmentation for health
      organizations, and to illustrate the process of segmenting health populations
      based on preference coefficients from a discrete choice conjoint experiment (DCE)
      using an example study of prevention of cyberbullying among university students.
      We followed a two-level procedure for investigating segmentation incorporating
      several methods for forming segments in Level 1 using DCE preference coefficients
      and testing their quality, reproducibility, and usability by health decision
      makers. Covariates (demographic, behavioral, lifestyle, and health state
      variables) were included in Level 2 to further evaluate quality and to support
      the scoring of large databases and developing typing tools for assigning those in
      the relevant population, but not in the sample, to the segments. Several
      segmentation solution candidates were found during the Level 1 analysis, and the
      relationship of the preference coefficients to the segments was investigated
      using predictive methods. Those segmentations were tested for their quality and
      reproducibility and three were found to be very close in quality. While one
      seemed better than others in the Level 1 analysis, another was very similar in
      quality and proved ultimately better in predicting segment membership using
      covariates in Level 2. The two segments in the final solution were profiled for
      attributes that would support the development and acceptance of cyberbullying
      prevention programs among university students. Those segments were very different
      where one wanted substantial penalties against cyberbullies and were willing to
      devote time to a prevention program, while the other felt no need to be involved
      in prevention and wanted only minor penalties. Segmentation recognizes key
      differences in why patients and physicians prefer different health programs and
      treatments. A viable segmentation solution may lead to adapting prevention
      programs and treatments for each targeted segment and/or to educating and
      communicating to better inform those in each segment of the program/treatment
      benefits. Segment members' revealed preferences showing behavioral changes
      provide the ultimate basis for evaluating the segmentation benefits to the health
      organization. 

PMID- 24327339
TI  - The intestinal microbiota interferes with the microRNA response upon oral
      Listeria infection.
AB  - The intestinal tract is the largest reservoir of microbes in the human body. The
      intestinal microbiota is thought to be able to modulate alterations of the gut
      induced by enteropathogens, thereby maintaining homeostasis. Listeria
      monocytogenes is the agent of listeriosis, an infection transmitted to humans
      upon ingestion of contaminated food. Crossing of the intestinal barrier is a
      critical step of the infection before dissemination into deeper organs. Here, we
      investigated the role of the intestinal microbiota in the regulation of host
      protein-coding genes and microRNA (miRNA or miR) expression during Listeria
      infection. We first established the intestinal miRNA signatures corresponding to
      the 10 most highly expressed miRNAs in the murine ileum of conventional and
      germfree mice, noninfected and infected with Listeria. Next, we identified 6
      miRNAs whose expression decreased upon Listeria infection in conventional mice.
      Strikingly, five of these miRNA expression variations (in miR-143, miR-148a, miR
      200b, miR-200c, and miR-378) were dependent on the presence of the microbiota. In
      addition, as is already known, protein-coding genes were highly affected by
      infection in both conventional and germfree mice. By crossing bioinformatically
      the predicted targets of the miRNAs to our whole-genome transcriptomic data, we
      revealed an miRNA-mRNA network that suggested miRNA-mediated global regulation
      during intestinal infection. Other recent studies have revealed an miRNA response
      to either bacterial pathogens or commensal bacteria. In contrast, our work
      provides an unprecedented insight into the impact of the intestinal microbiota on
      host transcriptional reprogramming during infection by a human pathogen.
      IMPORTANCE: While the crucial role of miRNAs in regulating the host response to
      bacterial infection is increasingly recognized, the involvement of the intestinal
      microbiota in the regulation of miRNA expression has not been explored in detail.
      Here, we investigated the impact of the intestinal microbiota on the regulation
      of protein-coding genes and miRNA expression in a host infected by L.
      monocytogenes, a food-borne pathogen. We show that the microbiota interferes with
      the microRNA response upon oral Listeria infection and identify several protein
      coding target genes whose expression correlates inversely with that of the miRNA.
      Further investigations of the regulatory networks involving miR-143, miR-148a,
      miR-200b, miR-200c, and miR-378 will provide new insights into the impact of the
      intestinal microbiota on the host upon bacterial infection.

PMID- 24327340
TI  - Cytokeratin 8 is an epithelial cell receptor for Pet, a cytotoxic serine protease
      autotransporter of Enterobacteriaceae.
AB  - The group of proteins known as serine protease autotransporters of
      Enterobacteriaceae (SPATE) is a growing family of serine proteases secreted to
      the external milieu by the type V secretion system. Pet toxin and some other
      SPATE belong to the class 1 cytotoxic SPATE, which have comparable protease
      strength on fodrin. Pet is internalized and is directed to its intracellular
      substrate by retrograde transport. However, the epithelial cell receptor for Pet
      has yet to be identified. We show that Pet has affinity for the epithelial cell
      surface until the saturation of the binding sites at 100 nM Pet. Affinity column
      assays and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)
      analysis identified a cytokeratin (CK8) which directly binds to Pet, and both
      proteins colocalized on the cell surface. Interestingly, CK8 is not present in
      kidney cell lines, which are not susceptible to Pet. Inhibition experiments by
      using anti-CK8 and ck8 small interfering RNA (siRNA) blocked the cytotoxic effect
      induced by Pet, while exogenous CK8 expression in kidney cells made them
      susceptible to Pet intoxication. Recombinant CK8 showed a Pet-binding pattern
      similar to that seen by using fixed cells. Remarkably, Pet colocalized with CK8
      and clathrin at early times (receptor-mediated endocytosis), and subsequently,
      Pet colocalized with CK8 and Rab5b in the early endosomes. These data support the
      idea that CK8 is an important receptor for Pet on epithelial cells for starting
      its cytotoxic effects. These data suggest that therapeutics that block Pet-CK8
      interaction may improve outcome of diseases caused by Pet-secreting
      Enterobacteriaceae such as enteroaggregative Escherichia coli. IMPORTANCE:
      Receptor-ligand binding is one mechanism by which cells sense and respond to
      external cues. Receptors may also be utilized by toxins to mediate their own
      internalization. Pet toxin is secreted by enteroaggregative Escherichia coli, an
      organism that causes persistent diarrhea in children, traveler's diarrhea, and
      acute and persistent diarrhea in patients with HIV. Pet is a member of the family
      of serine protease autotransporters of Enterobacteriaceae (SPATE). SPATE in
      different pathogens are virulence factors, and Pet belongs to the class 1
      cytotoxic SPATE, which have comparable protease strength on their biological
      substrate, fodrin (a cytoskeletal protein important for maintaining cell
      viability). To cleave fodrin, Pet enters the cells by clathrin-mediated
      endocytosis. This mechanism includes receptor-mediated endocytosis (a receptor
      ligand complex triggers the endocytosis). We show that CK8 is an important
      receptor for Pet on epithelial cells and that it may be useful for identifying
      molecules that block the interaction of CK8 with Pet.

PMID- 24327341
TI  - MinC, MinD, and MinE drive counter-oscillation of early-cell-division proteins
      prior to Escherichia coli septum formation.
AB  - Bacterial cell division initiates with the formation of a ring-like structure at
      the cell center composed of the tubulin homolog FtsZ (the Z-ring), which acts as
      a scaffold for the assembly of the cell division complex, the divisome. Previous
      studies have suggested that the divisome is initially composed of FtsZ polymers
      stabilized by membrane anchors FtsA and ZipA, which then recruit the remaining
      division proteins. The MinCDE proteins prevent the formation of the Z-ring at
      poles by oscillating from pole to pole, thereby ensuring that the concentration
      of the Z-ring inhibitor, MinC, is lowest at the cell center. We show that prior
      to septum formation, the early-division proteins ZipA, ZapA, and ZapB, along with
      FtsZ, assemble into complexes that counter-oscillate with respect to MinC, and
      with the same period. We propose that FtsZ molecules distal from high
      concentrations of MinC form relatively slowly diffusing filaments that are bound
      by ZapAB and targeted to the inner membrane by ZipA or FtsA. These complexes may
      facilitate the early stages of divisome assembly at midcell. As MinC oscillates
      toward these complexes, FtsZ oligomerization and bundling are inhibited, leading
      to shorter or monomeric FtsZ complexes, which become less visible by
      epifluorescence microscopy because of their rapid diffusion. Reconstitution of
      FtsZ-Min waves on lipid bilayers shows that FtsZ bundles partition away from high
      concentrations of MinC and that ZapA appears to protect FtsZ from MinC by
      inhibiting FtsZ turnover. IMPORTANCE: A big issue in biology for the past 100
      years has been that of how a cell finds its middle. In Escherichia coli, over 20
      proteins assemble at the cell center at the time of division. We show that the
      MinCDE proteins, which prevent the formation of septa at the cell pole by
      inhibiting FtsZ, drive the counter-oscillation of early-cell-division proteins
      ZapA, ZapB, and ZipA, along with FtsZ. We propose that FtsZ forms filaments at
      the pole where the MinC concentration is the lowest and acts as a scaffold for
      binding of ZapA, ZapB, and ZipA: such complexes are disassembled by MinC and
      reform within the MinC oscillation period before accumulating at the cell center
      at the time of division. The ability of FtsZ to be targeted to the cell center in
      the form of oligomers bound by ZipA and ZapAB may facilitate the early stages of
      divisome assembly.

PMID- 24327342
TI  - Dissecting the machinery that introduces disulfide bonds in Pseudomonas
      aeruginosa.
AB  - Disulfide bond formation is required for the folding of many bacterial virulence
      factors. However, whereas the Escherichia coli disulfide bond-forming system is
      well characterized, not much is known on the pathways that oxidatively fold
      proteins in pathogenic bacteria. Here, we report the detailed unraveling of the
      pathway that introduces disulfide bonds in the periplasm of the human pathogen
      Pseudomonas aeruginosa. The genome of P. aeruginosa uniquely encodes two DsbA
      proteins (P. aeruginosa DsbA1 [PaDsbA1] and PaDsbA2) and two DsbB proteins
      (PaDsbB1 and PaDsbB2). We found that PaDsbA1, the primary donor of disulfide
      bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and
      PaDsbB2. In vitro reconstitution of the pathway confirms that both PaDsbB1 and
      PaDsbB2 shuttle electrons from PaDsbA1 to membrane-bound quinones. Accordingly,
      deletion of both P. aeruginosa dsbB1 (PadsbB1) and PadsbB2 is required to prevent
      the folding of several P. aeruginosa virulence factors and to lead to a
      significant decrease in pathogenicity. Using a high-throughput proteomic
      approach, we also analyzed the impact of PadsbA1 deletion on the global
      periplasmic proteome of P. aeruginosa, which allowed us to identify more than 20
      new potential substrates of this major oxidoreductase. Finally, we report the
      biochemical and structural characterization of PaDsbA2, a highly oxidizing
      oxidoreductase, which seems to be expressed under specific conditions. By fully
      dissecting the machinery that introduces disulfide bonds in P. aeruginosa, our
      work opens the way to the design of novel antibacterial molecules able to disarm
      this pathogen by preventing the proper assembly of its arsenal of virulence
      factors. IMPORTANCE: The human pathogen Pseudomonas aeruginosa causes life
      threatening infections in immunodepressed and cystic fibrosis patients. The
      emergence of P. aeruginosa strains resistant to all of the available
      antibacterial agents calls for the urgent development of new antibiotics active
      against this bacterium. The pathogenic power of P. aeruginosa is mediated by an
      arsenal of extracellular virulence factors, most of which are stabilized by
      disulfide bonds. Thus, targeting the machinery that introduces disulfide bonds
      appears to be a promising strategy to combat P. aeruginosa. Here, we unraveled
      the oxidative protein folding system of P. aeruginosa in full detail. The system
      uniquely consists of two membrane proteins that generate disulfide bonds de novo
      to deliver them to P. aeruginosa DsbA1 (PaDsbA1), a soluble oxidoreductase.
      PaDsbA1 in turn donates disulfide bonds to secreted proteins, including virulence
      factors. Disruption of the disulfide bond formation machinery dramatically
      decreases P. aeruginosa virulence, confirming that disulfide formation systems
      are valid targets for the design of antimicrobial drugs.

PMID- 24327344
TI  - Blood-brain barrier and traumatic brain injury.
AB  - The blood-brain barrier (BBB) is an anatomical microstructural unit, with several
      different components playing key roles in normal brain physiological regulation.
      Formed by tightly connected cerebrovascular endothelial cells, its normal
      function depends on paracrine interactions between endothelium and closely
      related glia, with several recent reports stressing the need to consider the
      entire gliovascular unit in order to explain the underlying cellular and
      molecular mechanisms. Despite that, with regard to traumatic brain injury (TBI)
      and significant events in incidence and potential clinical consequences in
      pediatric and adult ages, little is known about the actual role of BBB disruption
      in its diverse pathological pathways. This Mini-Review addresses the current
      literature on possible factors affecting gliovascular units and contributing to
      posttraumatic BBB dysfunction, including neuroinflammation and disturbed
      transport mechanisms along with altered permeability and consequent posttraumatic
      edema. Key mechanisms and its components are described, and promising lines of
      basic and clinical research are identified, because further knowledge on BBB
      pathological interference should play a key role in understanding TBI and provide
      a basis for possible therapeutic targets in the near future, whether through
      restoration of normal BBB function after injury or delivering drugs in an
      increased permeability context, preventing secondary damage and improving
      functional outcome.

PMID- 24327343
TI  - The histone code of Toxoplasma gondii comprises conserved and unique
      posttranslational modifications.
AB  - Epigenetic gene regulation has emerged as a major mechanism for gene regulation
      in all eukaryotes. Histones are small, basic proteins that constitute the major
      protein component of chromatin, and posttranslational modifications (PTM) of
      histones are essential for epigenetic gene regulation. The different combinations
      of histone PTM form the histone code for an organism, marking functional units of
      chromatin that recruit macromolecular complexes that govern chromatin structure
      and regulate gene expression. To characterize the repertoire of Toxoplasma gondii
      histone PTM, we enriched histones using standard acid extraction protocols and
      analyzed them with several complementary middle-down and bottom-up proteomic
      approaches with the high-resolution Orbitrap mass spectrometer using collision
      induced dissociation (CID), higher-energy collisional dissociation (HCD), and/or
      electron transfer dissociation (ETD) fragmentation. We identified 249 peptides
      with unique combinations of PTM that comprise the T. gondii histone code. T.
      gondii histones share a high degree of sequence conservation with human histones,
      and many modifications are conserved between these species. In addition, T.
      gondii histones have unique modifications not previously identified in other
      species. Finally, T. gondii histones are modified by succinylation,
      propionylation, and formylation, recently described histone PTM that have not
      previously been identified in parasitic protozoa. The characterization of the T.
      gondii histone code will facilitate in-depth analysis of how epigenetic
      regulation affects gene expression in pathogenic apicomplexan parasites and
      identify a new model system for elucidating the biological functions of novel
      histone PTM. IMPORTANCE: Toxoplasma gondii is among the most common parasitic
      infections in humans. The transition between the different stages of the T.
      gondii life cycle are essential for parasite virulence and survival. These
      differentiation events are accompanied by significant changes in gene expression,
      and the control mechanisms for these transitions have not been elucidated.
      Important mechanisms that are involved in the control of gene expression are the
      epigenetic modifications that have been identified in several eukaryotes. T.
      gondii has a full complement of histone-modifying enzymes, histones, and
      variants. In this paper, we identify over a hundred PTM and a full repertoire of
      PTM combinations for T. gondii histones, providing the first large-scale
      characterization of the T. gondii histone code and an essential initial step for
      understanding how epigenetic modifications affect gene expression and other
      processes in this organism.

PMID- 24327346
TI  - Neuroprotection against permanent focal cerebral ischemia by ginkgolides A and B
      is associated with obstruction of the mitochondrial apoptotic pathway via
      inhibition of c-Jun N-terminal kinase in rats.
AB  - We have previously reported that ginkgolides containing ginkgolides A and B
      (GKAB) reduce infarct size in a rat model of focal ischemia. c-Jun N-terminal
      kinase (JNK), also known as stress-activated kinase (SAPK), is a critical stress
      responsive kinase activated by various brain insults. Previous studies have
      demonstrated a brief increase in p-SAPK/JNK levels after focal ischemic brain
      injuries. In this study, we sought to investigate whether the neuroprotective
      effects of GKAB in rat models of permanent focal cerebral ischemia are associated
      with the JNK signaling pathway. Sprague-Dawley rats were subjected to permanent
      middle cerebral artery occlusion by intraluminal suture blockade. GKAB was
      injected intravenously immediately after ischemia onset. Here we demonstrate in
      rats that GKAB reduces neuronal apoptosis and blocks the increase of p-SAPK/JNK
      levels and nuclear translocation after cerebral ischemia in a dose-dependent
      manner. Furthermore, we report that cerebral ischemia increases ischemia-induced
      induction of reactive oxygen species, and this effect was blocked by GKAB. In
      addition, we show that BimL is induced and attenuated by GKAB. GKAB also
      repressed the ischemia-induced increase in the expression of Bax and reversed the
      decline in expression of Bcl-2. Likewise, there was a reduction in the release or
      activation of several mitochondrial proapoptotic molecules, including cytochrome
      c, caspases 3 and 9, and PARP. Taken together, our findings strongly suggest that
      GKAB-mediated neuroprotective effects against focal ischemia act through the
      inhibition of p-SAPK/JNK activation, in which the obstruction of the
      mitochondrial apoptotic pathway via the JNK signaling pathway is a key downstream
      mechanism of GKAB.

PMID- 24327347
TI  - Neurofilament-tubulin binding site peptide NFL-TBS.40-63 increases the
      differentiation of oligodendrocytes in vitro and partially prevents them from
      lysophosphatidyl choline toxiciy.
AB  - During multiple sclerosis (MS), the main axon cystoskeleton proteins,
      neurofilaments (NF), are altered, and their release into the cerebrospinal fluid
      correlates with disease severity. The role of NF in the extraaxonal location is
      unknown. Therefore, we tested whether synthetic peptides corresponding to the
      tubulin-binding site (TBS) sequence identified on light NF chain (NFL-TBS.40-63)
      and keratin (KER-TBS.1-24), which could be released during MS, modulate
      remyelination in vitro. Biotinylated NFL-TBS.40-63, NFL-Scramble2, and KER-TBS.1
      54 (1-100 MUM, 24 hr) were added to rat oligodendrocyte (OL) and astrocyte (AS)
      cultures, grown in chemically defined medium. Proliferation and differentiation
      were characterized by using specific antibodies (A2B5, CNP, MBP, GFAP) and
      compared with untreated cultures. Lysophosphatidyl choline (LPC; 2 * 10(-5) M)
      was used to induce OL death and to test the effects of TBS peptides under these
      conditions. NFL-TBS.40-63 significantly increased OL differentiation and
      maturation, with more CNP(+) and MBP(+) cells characterized by numerous ramified
      processes, along with myelin balls. When OL were challenged with LPC, concomitant
      treatment with NFL-TBS.40-63 rescued more than 50% of OL compared with cultures
      treated with LPC only. Proliferation of OL progenitors was not affected, nor were
      AS proliferation and differentiation. NFL-TBS.40-63 peptide induces specific
      effects in vitro, increasing OL differentiation and maturation without altering
      AS fate. In addition, it partially protects OL from demyelinating injury. Thus
      release of NFL-TBS.40-63 caused by axonal damage in vivo could improve repair
      through increased OL differentiation, which is a prerequisite for remyelination.

PMID- 24327345
TI  - Intracellular distribution of differentially phosphorylated dual-specificity
      tyrosine phosphorylation-regulated kinase 1A (DYRK1A).
AB  - The gene encoding dual-specificity tyrosine phosphorylation-regulated kinase 1A
      (DYRK1A) is located within the Down syndrome (DS) critical region of chromosome
      21. DYRK1A interacts with a plethora of substrates in the cytosol, cytoskeleton,
      and nucleus. Its overexpression is a contributing factor to the developmental
      alterations and age-associated pathology observed in DS. We hypothesized that the
      intracellular distribution of DYRK1A and cell-compartment-specific functions are
      associated with DYRK1A posttranslational modifications. Fractionation showed
      that, in both human and mouse brain, almost 80% of DYRK1A was associated with the
      cytoskeleton, and the remaining DYRK1A was present in the cytosolic and nuclear
      fractions. Coimmunoprecipitation revealed that DYRK1A in the brain cytoskeleton
      fraction forms complexes with filamentous actin, neurofilaments, and tubulin. Two
      dimensional gel analysis of the fractions revealed DYRK1A with distinct
      isoelectric points: 5.5-6.5 in the nucleus, 7.2-8.2 in the cytoskeleton, and 8.7
      in the cytosol. Phosphate-affinity gel electrophoresis demonstrated several bands
      of DYRK1A with different mobility shifts for nuclear, cytoskeletal, and cytosolic
      DYRK1A, indicating modification by phosphorylation. Mass spectrometry analysis
      disclosed one phosphorylated site in the cytosolic DYRK1A and multiple
      phosphorylated residues in the cytoskeletal DYRK1A, including two not previously
      described. This study supports the hypothesis that intracellular distribution and
      compartment-specific functions of DYRK1A may depend on its phosphorylation
      pattern.

PMID- 24327348
TI  - Static versus vacuum cell seeding on high and low porosity ceramic scaffolds.
AB  - An adequate cell seeding technique is essential for effective bone regeneration
      on cell seeded constructs of porous tricalcium phosphates. In previous studies,
      dynamic cell seeding, in which an external force is applied to seed cells on a
      biomaterial, resulted in more homogeneous cell seeding in low porosity scaffolds
      than static seeding. The optimal cell seeding technique for high porosity
      scaffolds has not been defined yet. Human mesenchymal stem cells were isolated
      from bone marrow and characterized. The cells were seeded on low porosity (45%)
      and high porosity (90%) tricalcium phosphate scaffolds using a static and a
      vacuum seeding technique. LIVE/DEAD(r) staining of the cell-scaffold complexes
      followed by confocal laser scanning microscopy was used to measure cell
      proliferation, cell distribution and cell viability one, three and seven days
      after seeding. Cell proliferation was also quantified using a DNA quantification
      assay. Neither static nor vacuum seeding resulted in homogeneous cell seeding on
      both low and high porosity scaffolds. Cell density was lower on the inside than
      on the outside of the scaffolds. On low porosity scaffolds, the vacuum method
      yielded the highest numbers of cells compared to the static method. Low porosity
      scaffolds were seeded most homogeneously using the static seeding method. Seven
      days after seeding, numbers of adherent cells were comparable for both scaffold
      types and independent of the cell seeding technique used. In conclusion, on high
      porosity scaffolds, static seeding results in more homogeneous cell seeding and
      it is easier to use than a vacuum seeding technique.

PMID- 24327349
TI  - Effects of releasing recombinant human growth and differentiation factor-5 from
      poly(lactic-co-glycolic acid) microspheres for repair of the rat degenerated
      intervertebral disc.
AB  - PURPOSE: The objective of this study was to investigate the therapeutic potential
      of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with recombinant
      human growth and differentiation factor-5 (rhGDF-5) on the disc degeneration
      induced by needle puncture in a rat caudal disc model. METHODS: The rhGDF-5
      loaded PLGA microspheres were prepared by the water-oil-water double-emulsion
      solvent evaporation method, and release kinetics was determined over 42 days.
      Rats that underwent 21-G needle puncture at rat tail discs were injected with
      rhGDF-5/PLGA microspheres at four weeks after needle injury. At eight weeks after
      the injection, disc height, glycosaminoglycans content, and DNA content of the
      discs were evaluated. In addition, gene expression analysis of aggrecan, collagen
      type I, and collagen type II in the rat nucleus pulposus was measured by real
      time polymerase chain reaction. Rat discs were also assessed by histology using
      hematoxylin and eosin stain. RESULTS: Encapsulation of rhGDF-5 in PLGA
      microspheres guaranteed a sustained release of active rhGDF-5 for more than 42
      days. The injection of GDF-5/PLGA microspheres resulted in a statistically
      significant restoration of disc height (p < 0.01), improvement of sulfated
      glycosaminoglycan (p < 0.05), DNA content (p < 0.05), and significantly increased
      mRNA levels of collagen type II (p < 0.01), and the differentiation index (the
      ratio of collagen type II to collagen type I, p < 0.01). In addition, rhGDF
      5/PLGA microspheres treatment also improved histological changes induced by
      needle puncture. CONCLUSIONS: The results of this study suggest that injection of
      rhGDF-5 loaded in PLGA microspheres into rat tail discs may be as a promising
      therapy strategy to regenerate or repair the degenerative disc.

PMID- 24327350
TI  - A scalable approach to obtain mesenchymal stem cells with osteogenic potency on
      apatite microcarriers.
AB  - Bone tissue engineering, which relies on the interactions between stem cells and
      suitable scaffold materials, represents a highly desirable alternative to
      currently used allograft or autograft strategies for the treatment of bone
      defects caused by injury or disease, with one of the major challenges being to
      generate sufficient quantities of stem cells to bring about the intended
      therapeutic effect. However, conventional cell culture to achieve sufficient cell
      numbers faces limitations of low efficiency and diminished efficacy of stem cells
      due to repeated passaging. Furthermore, current microcarriers available may not
      be suitable for therapeutic implantation. Here, the authors featured an apatite
      based microcarrier intended for bone tissue engineering applications. These
      apatite microcarriers have a diameter of ~230 um, and exhibited porous and rough
      surface morphology. Peaks obtained from X-ray diffractometry (XRD) corresponded
      to hydroxyapatite (HA) with high crystallinity. Fourier transform infrared
      spectrophotometry (FTIR) showed that no residues of alginate remained, and all
      bands observed belong to phosphate and hydroxyl groups of HA. To evaluate the
      cytocompatibility of these microcarriers, in vitro proliferation studies were
      conducted and compared with conventional monolayer as well as Cytodex 3. The
      authors found that human foetal mesenchymal stem cells (hfMSCs) cultured on
      apatite microcarriers exhibited comparable growth characteristics, achieving 1.4
      fold higher live cells than Cytodex 3 over a 9-day culture period. As these
      microcarriers were hypothesised to offer enhanced osteogenic potency over
      conventional monolayer culture, alkaline phosphatase (ALP), type I collagen and
      osteocalcin expression of hfMSCs cultured on the apatite microcarriers were
      evaluated over a 12-day period. ALP expression for hfMSCs seeded on apatite
      microcarriers was 2.7-fold higher than that of adherent monolayer culture (p <
      0.001). Additionally, type I collagen and osteocalcin expression were 1.8- and
      1.5-fold higher than that of adherent monolayer culture on day 12, respectively
      (p < 0.001).

PMID- 24327351
TI  - Reduced graphene oxide functionalized with a luminescent rare-earth complex for
      the tracking and photothermal killing of drug-resistant bacteria.
AB  - An antibacterial platform based on multifunctional reduced graphene oxide (rGO)
      that is responsive to near-infrared (NIR) light has been constructed. By
      introducing a luminescent Eu(3+) complex and vancomycin for bacteria tracking
      into one system, this platform could specifically recognize and light up
      bacteria. Antibacterial activity of this nanoscale construction under NIR
      illumination was investigated. Upon illumination with NIR light, this nanoscale
      architecture generates great heat locally, resulting in the death of drug
      resistant bacteria. These results indicate that the ability of this nanoscale
      platform to kill drug-resistant bacteria has great potential for clinical
      pathogenic bacteria diagnosis and treatment. 

PMID- 24327352
TI  - [Decision process in a multidisciplinary cancer team with limited evidence].
AB  - BACKGROUND: The Head and Neck Cancer Tumor Board is a multispeciality
      comprehensive conference that brings together experts with different backgrounds
      to make group decisions about the appropriate treatment. Due to the complexity of
      the patient cases and the collaboration of different medical disciplines most of
      these decisions have to be made under uncertainty, i. e., with-out knowing all
      relevant factors and without being quite sure about the outcome. METHODS: To
      develop effective team decision making under uncertainty, it is necessary to
      understand how medical experts perceive and handle uncertainties. The aim of this
      field study was to develop a knowledge base by exploring additionally the factors
      that influence group decision making processes. A structured nonparticipant
      observational study was employed to address the research goal. Video data were
      analyzed by 2 independent observers using an observation checklist. A total of 20
      videotaped case discussions were studied. Observations were complemented by a
      questionnaire gathering subjective evaluations of board members about the process
      and quality of their decisions (N=15). RESULTS: The results show that uncertainty
      is recognized by board members. Reasons for uncertainty may stem from the
      complexity of the cases (e. g. therapy options) or the assessment from different
      disciplines coming together at the board. CONCLUSION: With respect to handling
      uncertainty and guaranteeing an optimal decision making process potential for
      improvement could be defined. This pertains to the handling of different levels
      of competence, the promotion of a positive discussion culture as well as
      structuring of the decision making process.

PMID- 24327353
TI  - [Social integration and its relevance for quality of life after laryngectomy].
AB  - BACKGROUND: Social networks and social participation generally have positive
      effects on health. Yet, little is known about how patients after total
      laryngectomy (TLE) are integrated into the society. Aim of this study was to
      investigate how patients are socially integrated after a TLE and if social
      integration is associated with certain areas of quality of life. PATIENTS AND
      METHODS: In a longitudinal multi-centred study 161 laryngectomees were
      interviewed 1 year after the total laryngectomy. Social integration was measured
      on the basis of an index formed by the questionnaire "Psychosocial Adjustment
      after Laryngectomy" and questions about social support. To assess quality of
      life, we used the questionnaire from the European Organisation for Research and
      Treatment of Cancer EORTC QLQ-C30. RESULTS: 58% of all patients are well
      integrated 1 year after surgery. Well integrated persons have less problems in
      different components of quality of life. They report higher levels of social (OR
      4.07; CI: 1.96-8.47) and role functioning (OR 3.59; CI: 1.61-8.02). Successful
      social integration is also associated with higher emotional well-being (OR 8.57;
      CI: 3.59-20.46). CONCLUSIONS: There is evidence that 1 year after TLE only about
      half of the patients feel socially integrated. Because of the negative
      association of poor social integration with social, emotional and role
      functioning, patients should be supported in their attempts to take actively part
      in social life.

PMID- 24327354
TI  - Sperm nuclear proteome and its epigenetic potential.
AB  - The main function of the sperm cell is to transmit the paternal genetic message
      and epigenetic information to the embryo. Importantly, the majority of the genes
      in the sperm chromatin are highly condensed by protamines, whereas genes
      potentially needed in the initial stages of development are associated with
      histones, representing a form of epigenetic marking. However, so far little
      attention has been devoted to other sperm chromatin-associated proteins that, in
      addition to histones and protamines, may also have an epigenetic role. Therefore,
      with the goal of contributing to cover this subject we have compiled, reviewed
      and report a list of 581 chromatin or nuclear proteins described in the human
      sperm cell. Furthermore, we have analysed their Gene Ontology Biological Process
      enriched terms and have grouped them into different functional categories.
      Remarkably, we show that 56% of the sperm nuclear proteins have a potential
      epigenetic activity, being involved in at least one of the following functions:
      chromosome organization, chromatin organization, protein-DNA complex assembly,
      DNA packaging, gene expression, transcription, chromatin modification and histone
      modification. In addition, we have also included and compared the sperm cell
      proteomes of different model species, demonstrating the existence of common
      trends in the chromatin composition in the mammalian mature male gamete. Taken
      together, our analyses suggest that the mammalian sperm cell delivers to the
      offspring a rich combination of histone variants, transcription factors,
      chromatin-associated and chromatin-modifying proteins which have the potential to
      encode and transmit an extremely complex epigenetic information.

PMID- 24327355
TI  - Silica: a lung carcinogen.
AB  - Silica has been known to cause silicosis for centuries, and evidence that silica
      causes lung cancer has accumulated over the last several decades. This article
      highlights 3 important developments in understanding the health effects of silica
      and preventing illness and death from silica exposure at work. First, recent
      epidemiologic studies have provided new information about silica and lung cancer.
      This includes detailed exposure-response data, thereby enabling the quantitative
      risk assessment needed for regulation. New studies have also shown that excess
      lung mortality occurs in silica-exposed workers who do not have silicosis and who
      do not smoke. Second, the US Occupational Safety and Health Administration has
      recently proposed a new rule lowering the permissible occupational limit for
      silica. There are approximately 2 million US workers currently exposed to silica.
      Risk assessments estimate that lowering occupational exposure limits from the
      current to the proposed standard will reduce silicosis and lung cancer mortality
      to approximately one-half of the rates predicted under the current standard.
      Third, low-dose computed tomography scanning has now been proven to be an
      effective screening method for lung cancer. For clinicians, asking about
      occupational history to determine if silica exposure has occurred is recommended.
      If such exposure has occurred, extra attention might be given to the early
      detection of silicosis and lung cancer, as well as extra emphasis on quitting
      smoking.

PMID- 24327356
TI  - Next-generation technologies and data analytical approaches for epigenomics.
AB  - Epigenetics refers to the collection of heritable features that modulate the
      genome-environment interaction without being encoded in the actual DNA sequence.
      While being mitotically and sometimes even meiotically transmitted, epigenetic
      traits often demonstrate extensive flexibility. This allows cells to acquire
      diverse gene expression patterns during differentiation, but also to adapt to a
      changing environment. However, epigenetic alterations are not always beneficial
      to the organism, as they are, for example, frequently identified in human
      diseases such as cancer. Accurate and cost-efficient genome-scale profiling of
      epigenetic features is thus of major importance to pinpoint these "epimutations,"
      for example, to monitor the epigenetic impact of environmental exposure. Over the
      last decade, the field of epigenetics has been revolutionized by several
      innovative "epigenomics" technologies exactly addressing this need. In this
      review, we discuss and compare widely used next-generation methods to assess DNA
      methylation and hydroxymethylation, noncoding RNA expression, histone
      modifications, and nucleosome positioning. Although recent methods are typically
      based on "second-generation" sequencing, we also pay attention to still commonly
      used array- and PCR-based methods, and look forward to the additional advantages
      of single-molecule sequencing. As the current bottleneck in epigenomics research
      is the analysis rather than generation of data, the basic difficulties and
      problem-solving strategies regarding data preprocessing and statistical analysis
      are introduced for the different technologies. Finally, we also consider the
      complications associated with epigenomic studies of species with yet unsequenced
      genomes and possible solutions.

PMID- 24327357
TI  - Atypical presentation of late-onset Tay-Sachs disease.
AB  - INTRODUCTION: Late-onset Tay-Sachs disease (LOTS) is a lysosomal storage disease
      caused by deficient Beta-hexosaminidase A activity. METHODS: We describe a 53
      year-old woman who presented with adult-onset leg weakness, and whose initial
      diagnosis was progressive muscular atrophy without identifiable etiology.
      Development of cerebellar ataxia in mid-life prompted reassessment. RESULTS: Beta
      hexosaminidase A quantification assay demonstrated absence of the isozyme.
      Genetic testing identified compound heterozygous mutations in the HEXA gene,
      confirming the diagnosis of LOTS. CONCLUSIONS: The phenotypic spectrum of LOTS
      includes motor neuronopathy, ataxia, choreoathetosis, neuropathy, and psychiatric
      symptoms in various combinations. This patient highlights the emergence of
      different clinical features over many years and emphasizes the need to consider
      LOTS in the differential diagnosis of progressive muscular atrophy.

PMID- 24327359
TI  - The prevalence of latex sensitisation and allergy and associated risk factors
      among healthcare workers using hypoallergenic latex gloves at King Edward VIII
      Hospital, KwaZulu-Natal South Africa: a cross-sectional study.
AB  - OBJECTIVES: The present study describes latex sensitisation and allergy
      prevalence and associated factors among healthcare workers using hypoallergenic
      latex gloves at King Edward VIII Hospital in KwaZulu-Natal, South Africa. DESIGN:
      Cross-sectional study. SETTING: A tertiary hospital in eThekwini municipality,
      KwaZulu-Natal, South Africa. PARTICIPANTS: 600 healthcare workers were randomly
      selected and 501 (337 exposed and 164 unexposed) participated. Participants who
      were pregnant, with less than 1 year of work as a healthcare worker and a history
      of anaphylactic reaction were excluded from the study. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Latex sensitisation and latex allergy were the outcome of
      interest and they were successfully measured. RESULTS: The prevalence of latex
      sensitisation and allergy was observed among exposed workers (7.1% and 5.9%) and
      unexposed workers (3.1% and 1.8%). Work-related allergy symptoms were
      significantly higher in exposed workers (40.9%, p<0.05). Duration of employment
      was inversely associated with latex allergy (OR 0.9; 95% CI 0.8 to 0.9). The risk
      of latex sensitisation (OR 4.2; 95% CI 1.2 to 14.1) and allergy (OR 5.1; 95% CI
      1.2 to 21.2) increased with the exclusive use of powder-free latex gloves. A dose
      response relationship was observed for powdered latex gloves (OR 1.1; 95% CI 1.0
      to 1.2). Atopy (OR 1.5; 95% CI 0.7 to 3.3 and OR 1.4; 95% CI 0.6 to 3.2) and
      fruit allergy (OR 2.3; 95% CI 0.8 to 6.7 and OR 3.1; 95% CI 1.1 to 9.2) also
      increased the risk of latex sensitisation and allergy. CONCLUSIONS: This study
      adds to previous findings that healthcare workers exposed to hypoallergenic latex
      gloves are at risk for developing latex sensitisation highlighting its importance
      as an occupational hazard in healthcare. More research is needed to identify the
      most cost effective way of implementing a latex-free environment in resource
      limited countries, such as South Africa. In addition more cohort analysis is
      required to better understand the chronicity of illness and disability associated
      with latex allergy.

PMID- 24327358
TI  - Properties of human blood monocytes. II. Monocytes from healthy adults are highly
      heterogeneous within and among individuals.
AB  - BACKGROUND: Human blood monocytes are known to include subsets defined by the
      expression of CD14 and CD16 but otherwise are often assumed to be relatively
      homogeneous. However, we had observed additional heterogeneity that led us to a
      more extensive examination of monocytes. METHODS: Blood samples from 200 healthy
      adults without known immunological abnormalities were examined by analysis with a
      hematology analyzer and by flow cytometry (FCM) to determine leukocyte
      differential counts, to identify subsets and to measure expression of monocyte
      associated molecules. RESULTS: The estimated cell counts of monocytes,
      neutrophils, total lymphocytes, and T cells all varied to a similar extent, that
      is, +/-30-35%. The fractions of monocyte subsets defined by CD14 and CD16 or by
      CD163 expression also varied among individuals. FCM examinations showed that all
      the monocyte-associated molecules that were examined varied in expression in this
      increasing order-CD244, CD4, CD38, CD91, CD11b, toll-like receptor 2 (TLR2), TIA
      1, CD14 (on CD14(Br+) cells), CD86, CD80, HLA-DQ, CD33, and HLA-DR. CONCLUSIONS:
      Human blood monocytes are heterogeneous among healthy adults with respect to cell
      counts, subsets, and the levels of expression of monocyte-associated molecules.
      An increase in the "non-classical" (CD14(Lo/Neg) /CD16(+) ) monocyte subset or in
      the expression of CD11b or TLR2 have known diagnostic/prognostic implications.
      CD244 and CD4 have well-defined functions on lymphocytes but perform unknown
      activities on monocytes although their expression appears more narrowly
      controlled. Together, these data suggest that monocytes should be more
      extensively examined in both clinical and basic contexts.

PMID- 24327360
TI  - Differences in research funding for women scientists: a systematic comparison of
      UK investments in global infectious disease research during 1997-2010.
AB  - OBJECTIVES: There has not previously been a systematic comparison of awards for
      research funding in infectious diseases by sex. We investigated funding awards to
      UK institutions for all infectious disease research from 1997 to 2010, across
      disease categories and along the research and development continuum. DESIGN:
      Systematic comparison. METHODS: Data were obtained from several sources for
      awards from the period 1997 to 2010 and each study assigned to-disease
      categories; type of science (preclinical, phases I-III trials, product
      development, implementation research); categories of funding organisation. Fold
      differences and statistical analysis were used to compare total investment, study
      numbers, mean grant and median grant between men and women. RESULTS: 6052 studies
      were included in the final analysis, comprising 4357 grants (72%) awarded to men
      and 1695 grants (28%) awarded to women, totalling L2.274 billion. Of this, men
      received L1.786 billion (78.5%) and women L488 million (21.5%). The median value
      of award was greater for men (L179 389; IQR L59 146-L371 977) than women (L125
      556; IQR L30 982-L261 834). Awards were greater for male principal investigators
      (PIs) across all infectious disease systems, excepting neurological infections
      and sexually transmitted infections. The proportion of total funding awarded to
      women ranged from 14.3% in 1998 to 26.8% in 2009 (mean 21.4%), and was lowest for
      preclinical research at 18.2% (L285.5 million of L1.573 billion) and highest for
      operational research at 30.9% (L151.4 million of L489.7 million). CONCLUSIONS:
      There are consistent differences in funding received by men and women PIs: women
      have fewer funded studies and receive less funding in absolute and in relative
      terms; the median funding awarded to women is lower across most infectious
      disease areas, by funder, and type of science. These differences remain broadly
      unchanged over the 14-year study period.

PMID- 24327361
TI  - Return to work following unintentional injury: a prospective follow-up study.
AB  - OBJECTIVE: The aim of this study was to predict time off work following
      unintentional injuries due to accidents leading to hospital admission. DESIGN:
      Prospective 6-month follow-up study. SETTING: Department of Trauma Surgery of a
      University Hospital. PARTICIPANTS: Consecutively recruited victims of
      unintentional injuries (n=221) hospitalised for a minimum of 32 h including two
      consecutive nights. All the participants were aged 18-65 years and were able to
      participate in an assessment within 30 days of the accident. MAIN OUTCOME
      MEASURES: Interview-assessed number of days off work during the 6 months
      immediately following the accident. RESULTS: The patients' subjective appraisals
      of (1) accident severity and (2) their ability to cope with the resulting injury
      and its job-related consequences predicted time off work following the accident
      beyond the impact of the objective severity of their injury and the type of
      accident involved. CONCLUSIONS: The patients' subjective appraisals of the
      accident severity and of their ability to cope with its consequences are highly
      relevant for return to work after accidents. Extending the findings from previous
      studies on severely injured and otherwise preselected accident victims, this
      seems to apply to the whole spectrum of patients hospitalised with unintentional
      injuries.

PMID- 24327362
TI  - Accountable to whom, for what? An exploration of the early development of
      Clinical Commissioning Groups in the English NHS.
AB  - OBJECTIVE: One of the key goals of the current reforms in the English National
      Health Service (NHS) under the Health and Social Care Act, 2012, is to increase
      the accountability of those responsible for commissioning care for patients
      (clinical commissioning groups (CCGs)), while at the same time allowing them a
      greater autonomy. This study was set out to explore CCG's developing
      accountability relationships. DESIGN: We carried out detailed case studies in
      eight CCGs, using interviews, observation and documentary analysis to explore
      their multiple accountabilities. SETTING/PARTICIPANTS: We interviewed 91 people,
      including general practitioners, managers and governing body members in
      developing CCGs, and undertook 439 h of observation in a wide variety of
      meetings. RESULTS: CCGs are subject to a managerial, sanction-backed
      accountability to NHS England (the highest tier in the new organisational
      hierarchy), alongside a number of other external accountabilities to the public
      and to some of the other new organisations created by the reforms. In addition,
      unlike their predecessor commissioning organisations, they are subject to complex
      internal accountabilities to their members. CONCLUSIONS: The accountability
      regime to which CCGs are subject to is considerably more complex than that which
      applied their predecessor organisations. It remains to be seen whether the twin
      aspirations of increased autonomy and increased accountability can be realised in
      practice. However, this early study raises some important issues and concerns,
      including the risk that the different bodies to whom CCGs are accountable will
      have differing (or conflicting) agendas, and the lack of clarity over the
      operation of sanction regimes.

PMID- 24327363
TI  - Parent-led or baby-led? Associations between complementary feeding practices and
      health-related behaviours in a survey of New Zealand families.
AB  - OBJECTIVE: To determine feeding practices and selected health-related behaviours
      in New Zealand families following a 'baby-led' or more traditional 'parent-led'
      method for introducing complementary foods. DESIGN, SETTING AND PARTICIPANTS: 199
      mothers completed an online survey about introducing complementary foods to their
      infant. Participants were classified into one of four groups: 'adherent baby-led
      weaning (BLW)', the infant mostly or entirely fed themselves at 6-7 months; 'self
      identified BLW', mothers reported following BLW at 6-7 months but were using
      spoon-feeding at least half the time; 'parent-led feeding', the mother reported
      not having tried BLW; and 'unclassified method', the mother reported they were
      not following BLW at 6-7 months but reported the infant mostly or entirely fed
      themselves at 6-7 months. RESULTS: 8% were following 'adherent BLW', 21% 'self
      identified BLW' and 0% were following the 'unclassified method'. Compared with
      'self-identified BLW' and 'parent-led feeding', a higher proportion of the
      'adherent BLW' met the WHO recommendations to exclusively breastfeed for 6 months
      and to introduce complementary foods at 6 months. The 'adherent BLW' group was
      more likely to have family foods (p=0.018), and less likely (p=0.002) to have
      commercially prepared baby food. Both BLW groups were more likely to share meals
      with the family compared with 'parent-led feeding'. In contrast to 'self
      identified BLW' and 'parent-led feeding', the 'adherent BLW' group did not offer
      iron-fortified cereal as a first food. CONCLUSIONS: This study suggests that
      although many parents consider they follow BLW, a very few are following it
      strictly. The extent to which BLW was followed was associated with potential
      benefits (eg, sharing family meals) and risks (eg, low iron first foods)
      highlighting the importance for health professionals and researchers of
      accurately determining the extent of adherence to BLW.

PMID- 24327364
TI  - Exploring the implementation of the framework convention on tobacco control in
      four small island developing states of the Pacific: a qualitative study.
AB  - OBJECTIVES: To determine what variables influence the implementation of the
      Framework Convention on Tobacco Control (FCTC) in small island developing states
      of the Pacific and how they affect its success or failure. To explore how
      barriers can be overcome and opportunities utilised to ensure an effective FCTC
      implementation in the Pacific Islands. DESIGN: A mixed methods, multiple case
      study consisting of primarily qualitative data in the form of semistructured
      interviews, document analysis and opportunistic observation. SETTING: Field
      visits were undertaken to collect data in the Cook Islands, Vanuatu, Palau and
      Nauru. The key informants were interviewed in the major cities or islands of each
      respective country: Rarotonga, Port Vila, Koror and Nauru. PARTICIPANTS:
      Purposive sampling was used to select 39 informants, whose roles were associated
      with FCTC implementation. Most of the participants worked in health-oriented
      positions in the government and non-government organisations. RESULTS: Each
      country made a significant progress towards FCTC implementation. Overall, strong
      policy content, public support and limited pro-tobacco coalition activity were
      conducive to FCTC implementation, but the challenges were evident in the form of
      limited capacity, limited antitobacco coalition activity and limited political
      commitment outside the ministries of health in each country. CONCLUSIONS: Further
      efforts are needed for full FCTC implementation, through building capacity and
      using resources effectively, growing commitment to FCTC beyond the health sector,
      fostering growth in antitobacco coalition activity, exploiting the limited pro
      tobacco activity that may be present and garnering public support for tobacco
      control. These lessons may be particularly important for other small island
      developing states in the Pacific and developing countries elsewhere.

PMID- 24327365
TI  - Young people's use of NHS Direct: a national study of symptoms and outcome of
      calls for children aged 0-15.
AB  - OBJECTIVES: National Health Service (NHS) Direct provides 24/7 expert telephone
      based healthcare information and advice to the public in England. However,
      limited research has explored the reasons to why calls are made on behalf of
      young people, as such this study aimed to examine call rate (CR) patterns in
      younger people to enable a better understanding of the needs of this population
      in England. SETTING: NHS Direct, England, UK. PARTICIPANTS AND METHODS: CRs
      (expressed as calls/100 persons/annum) were calculated for all calls (N=358 503)
      made to NHS Direct by, or on behalf of, children aged 0-15 during the combined
      four '1-month' periods within a year (July 2010, October 2010, January 2011 and
      April 2011). chi&sup2; Analysis was used to determine the differences between
      symptom, outcome and date/time of call. RESULTS: For infants aged <1, highest CRs
      were found for 'crying' for male (n=14, 440, CR=13.61) and female (n=13 654,
      CR=13.46) babies, which is used as a universal assessment applied to all babies.
      High CRs were also found for symptoms relating to 'skin/hair/nails' and
      'colds/flu/sickness' for all age groups, whereby NHS Direct was able to support
      patients to self-manage and provide health information for these symptoms for
      59.7% and 51.4% of all cases, respectively. Variations in CRs were found for time
      and age, with highest peaks found for children aged 4-15 in the 15:00-23:00
      period and in children aged <1 in the 7:00-15:00 period. CONCLUSIONS: This is the
      first study to examine the symptoms and outcome of calls made to NHS Direct for
      and on behalf of young children. The findings revealed how NHS Direct has
      supported a range of symptoms through the provision of health information and
      self-care support which provides important information about service planning and
      support for similar telephone-based services.

PMID- 24327366
TI  - New data about the functional morphology of the chaetiferous leech-like annelids
      Acanthobdella peledina (Grube, 1851) and Paracanthobdella livanowi (Epshtein,
      1966) (Clitellata, Acanthobdellida).
AB  - Approximately 130 individuals of Acanthobdella peledina and 100 individuals of
      Paracanthobdella livanowi were studied. Morphometric measurements were taken to
      explore the body form. The digestive and the reproductive systems of leech-like
      annelids were analyzed for the first time in such a high number of specimens.
      Observation of A. peledina and P. livanowi revealed crucial differences in the
      reproductive system of the analyzed taxa, mostly regarding variation in the shape
      of the testisacs and the length of the ovisacs. The results of a digestive system
      analysis suggest that blood-sucking parasites of the order Acanthobdellida may
      also lead a predatory lifestyle. The presented findings support the taxonomic
      division of the order Acanthobdellida into the families Acanthobdellidae and
      Paracanthobdellidae. Multiple similarities between Acanthobdellida and Hirudinida
      were also discussed.

PMID- 24327367
TI  - Severe infection and autoimmune disease are associated with increased risk of
      mood disorders.

PMID- 24327368
TI  - [Test your knowledge].

PMID- 24327369
TI  - Single-nucleotide polymorphism, rs1799941 in the Sex Hormone-Binding Globulin
      (SHBG) gene, related to both serum testosterone and SHBG levels and the risk of
      myocardial infarction, type 2 diabetes, cancer and mortality in men: the Tromso
      Study.
AB  - Low testosterone levels are associated with metabolic and cardiovascular disease
      risk factor, and have been shown to predict type 2 diabetes mellitus (T2DM),
      myocardial infarction (MI) and all-cause mortality. It is not known if these
      associations are causal or not. Recently, it has been shown that the serum
      testosterone levels are associated with single-nucleotide polymorphisms (SNPs),
      and we therefore studied the associations between one of these SNPs, rs1799941 on
      the Sex Hormone-Binding Globulin (SHBG) gene, and MI, T2DM, cancer and death. DNA
      was prepared from men who participated in the fourth survey of the Tromso Study
      in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death
      and a randomly selected control group. For mortality, the observation time was
      set from 1994, and for the other endpoints from birth. The endpoint data were
      completed up to 2010-2013. Genetic analyses were successfully performed in 5309
      men, of whom 1454 were registered with MI, 638 with T2DM, 1534 with cancer and in
      2226 who had died. Men with the minor homozygote genotype had significantly
      higher levels of total testosterone (14.7%) and SHBG (24.7%) compared with men
      with the major homozygote genotype, whereas free testosterone levels did not
      differ significantly between the genotypes. The SNP rs1799941 was not
      significantly associated with MI, T2DM, cancer or mortality. Thus, our result
      does not support a causal relationship between total testosterone and SHBG and
      MI, T2DM, cancer or mortality, suggesting that low testosterone more likely is a
      marker of poor health. 

PMID- 24327370
TI  - Association of iron indices and type 2 diabetes: a meta-analysis of observational
      studies.
AB  - The literature on the role of body iron status in the development of type 2
      diabetes (T2D) in humans is inconsistent. We aimed to assess the association
      between iron indices and T2D by a meta-analysis of previously published studies.
      A systematic literature search was conducted in PubMed and EMBASE. Observational
      studies on the association of ferritin (when controlled for age and sex),
      transferrin saturation, soluble transferrin receptor and transferrin with T2D
      were included. Pooled association estimates were calculated using a random
      effects model. Forty-six eligible studies were identified. The pooled
      multivariable adjusted relative risks of T2D in the highest versus lowest
      quartile of ferritin levels were significantly elevated in both cross-sectional
      as well as prospective studies and after restriction to inflammation-adjusted
      studies [overall: 1.67 (95% CI 1.41-1.99)]. The mean difference indicated 43.54
      ng/mL (95% CI 28.14-58.94) higher ferritin levels in type 2 diabetic individuals.
      The relative risk for a transferrin saturation >= 50% was 1.59 (95% CI 1.28
      1.97), the mean difference was -1.92% [95% CI -2.99-(-0.85)]. Study-specific
      results of soluble transferrin receptor and transferrin levels were extremely
      heterogeneous. Ferritin and clinically elevated transferrin saturation were
      strongly associated with an increased risk of T2D, overall and in prospective
      studies. Ferritin was also significantly associated after multivariable
      adjustment including inflammation. Thus, the current evidence hints at a causal
      effect; however, publication bias and unmeasured confounding cannot be excluded.

PMID- 24327372
TI  - Functional assessment of expiratory flow pattern in feline lower airway disease.
AB  - Feline lower airway disease (FLAD) is a chronic respiratory disease of which
      there is a lack of information on functional assessment in current veterinary
      medicine. The purposes of this study were to investigate expiratory pattern and
      evaluate the diagnostic utility of functional parameters in cats with FLAD.
      Thirty-three client-owned cats (23 FLAD cats and 10 control cats) were studied.
      Under quiet tidal breathing, pseudo-tidal breathing flow-volume loop (pTBFVL) was
      obtained from a barometric whole body plethysmography (BWBP) device. There were
      significant differences in the shapes of expiratory, but not inspiratory, curves
      between FLAD and control cats. The incidence of the presence of concave
      expiratory curve indicating lower airway obstruction was 74% in FLAD cats. To
      assess the diagnostic utility of pTBFVL indices in cats with FLAD, area under the
      receiver-operator curve was 0.86 for PEF/EF50 (peak expiratory flow divided by
      expiratory flow at end expiratory volume plus 50% tidal volume); a cuff-off value
      of PEF/EF50 >1.51 distinguished normal from FLAD (73.9% sensitivity, 100%
      specificity). There were no significant differences in traditionally measured
      BWBP parameters (ie, enhanced pause) between cats with and without FLAD in the
      present study. In conclusion, underlying change on expiratory flow pattern during
      natural tidal breathing existed in FLAD cats, and selected pTBFVL indices were
      useful in discriminating FLAD from normal cats. Tidal breathing pattern depicted
      by pseudoflow-pseudovolume loops from a BWBP system could be a non-invasive tool
      for functional assessment in client-owned cats. 

PMID- 24327371
TI  - Survivorship care plans: is there buy-in from community oncology providers?
AB  - BACKGROUND: The Institute of Medicine recommended that survivors of cancer and
      their primary care providers receive survivorship care plans (SCPs) to summarize
      cancer treatment and plan ongoing care. However, the use of SCPs remains limited.
      METHODS: Oncology providers at 14 National Cancer Institute Community Cancer
      Centers Program hospitals completed a survey regarding their perceptions of SCPs,
      including barriers to implementation, strategies for implementation, the role of
      oncology providers, and the importance of topics in SCPs (diagnosis, treatment,
      recommended ongoing care, and the aspects of ongoing care that the oncology
      practice will provide). RESULTS: Among 245 providers (response rate of 70%), 52%
      reported ever providing any component of an SCP to patients. The most widely
      reported barriers were lack of personnel and time to create SCPs (69% and 64% of
      respondents, respectively). The most widely endorsed strategy among those using
      SCPs was the use of a template with prespecified fields; 94% of those who used
      templates found them helpful. For each topic of an SCP, although 87% to 89% of
      oncology providers believed it was very important for primary care providers to
      receive the information, only 58% to 65% of respondents believed it was very
      important for patients to receive the information. Furthermore, 33% to 38% of
      respondents reported mixed feelings regarding whether it was the responsibility
      of oncology providers to provide SCPs. CONCLUSIONS: Practices need additional
      resources to overcome barriers to implementing SCPs. We found resistance toward
      SCPs, particularly the perceived value for the survivor and the idea that
      oncology providers are responsible for SCP dissemination.

PMID- 24327373
TI  - Getting back to basics: on the need to define care in analyses of care.

PMID- 24327374
TI  - Psychiatry's new manual (DSM-5): ethical and conceptual dimensions.
AB  - The introduction of the Diagnostic and statistical manual of mental disorders
      (DSM-5) in May 2013 is being hailed as the biggest event in psychiatry in the
      last 10 years. In this paper I examine three important issues that arise from the
      new manual:(1) Expanding nosology: Psychiatry has again broadened its nosology to
      include human experiences not previously under its purview (eg, binge eating
      disorder, internet gaming disorder, caffeine use disorder, hoarding disorder,
      premenstrual dysphoric disorder). Consequence-based ethical concerns about this
      expansion are addressed, along with conceptual concerns about a confusion of
      "construct validity" and "conceptual validity" and a failure to distinguish
      between "disorder" and "non disordered conditions for which we help people."(2)
      The role of claims about societal impact in changes in nosology: Several changes
      in the DSM-5 involved claims about societal impact in their rationales. This is
      due in part to a new online open comment period during DSM development. Examples
      include advancement of science, greater access to treatment, greater public
      awareness of condition, loss of identify or harm to those with removed disorders,
      stigmatization, offensiveness, etc. I identify and evaluate four importantly
      distinct ways in which claims about societal impact might operate in DSM
      development. (3) Categorisation nosology to spectrum nosology: The move to
      "degrees of severity" of mental disorders, a major change for DSM-5, raises
      concerns about conceptual clarity and uniformity concerning what it means to have
      a severe form of a disorder, and ethical concerns about communication. 

PMID- 24327375
TI  - Debating DSM-5: diagnosis and the sociology of critique.
AB  - The development of the fifth edition of the American Psychiatric Association's
      Diagnostic and Statistical Manual of Mental Disorders-the DSM-5-has reenergised
      and driven further forward critical discourse about the place and role of
      diagnosis in mental health. The DSM-5 has attracted considerable criticism, not
      least about its role in processes of medicalisation. This paper suggests the need
      for a sociology of psychiatric critique. Sociological analysis can help map
      fields of contention, and cast fresh light on the assumptions and nuances of
      debate around the DSM-5; it underscores the importance of diagnosis to the
      governance of social and clinical life, as well as the wider discourses critical
      commentaries connect with and are activated by. More normatively, a sociology of
      critique can indicate which interests and values are structuring the dialogues
      being articulated, and just how diverse clinical opinion regarding the DSM can
      actually be. This has implications for the considerations of health services and
      policy decision-makers who might look to such debates for guidance. 

PMID- 24327376
TI  - Stereospecific multiple isotopic labeling of benzyl alcohol.
AB  - Isotopically labeled enzymatic substrates and biological metabolites are useful
      for many mechanistic analyses, particularly the study of kinetic and equilibrium
      isotope effects, determining the stereospecificity of enzymes, and resolving
      metabolic pathways. Here, we present the one-pot synthesis, purification, and
      kinetic analysis of 7R-[(2) H]-phenyl-[(14) C]-benzyl alcohol. The procedure
      involves a chemoenzymatic synthesis that couples formate dehydrogenase to alcohol
      dehydrogenase with a catalytic amount of nicotinamide cofactor. The reaction goes
      to completion overnight, and the measurement of a competitive kinetic isotope
      effect on the enzymatic oxidation of the purified product identified no (1) H
      contamination. This measurement is very sensitive to such isotopic contamination
      and verified the high level of isotopic and enantiomeric purity yielded by the
      new synthetic procedure.

PMID- 24327380
TI  - Shape-tailored polymer colloids on the road to become structural motifs for
      hierarchically organized materials.
AB  - Anisometric polymer colloids are likely to behave differently when compared with
      centrosymmetric particles. Their study may not only shine new light on the
      organization of matter; they may also serve as building units with specific
      symmetries and complexity to build new materials from them. Polymer colloids of
      well-defined complex geometries can be obtained by packing a limited number of
      spherical polymer particles into clusters with defined configurations. Such
      supracolloidal architectures can be fabricated at larger scales using narrowly
      dispersed emulsion droplets as templates. Assemblies built from at least two
      different types of particles as elementary building units open perspectives in
      selective targeting of colloids with specific properties, aiming for mesoscale
      building blocks with tailor-made morphologies and multifunctionality. Polymer
      colloids with defined geometries are also ideal to study shape-dependent
      properties such as the diffusion of complex particles. 

PMID- 24327377
TI  - Prenatal arsenic exposure and the epigenome: altered microRNAs associated with
      innate and adaptive immune signaling in newborn cord blood.
AB  - The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio,
      Mexico was recently established to better understand the impacts of prenatal
      exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40)
      of newborn cord blood samples for microRNA (miRNA) expression changes associated
      with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs)
      and maternal urine were assessed. Levels of DW-iAs ranged from below detectable
      values to 236 ug/L (mean = 51.7 ug/L). Total arsenic in maternal urine (U-tAs)
      was defined as the sum of iAs and its monomethylated and dimethylated metabolites
      (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 ug/L (mean = 64.5
      ug/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs
      with increasing expression associated with U-tAs. Transcriptional targets of the
      miRNAs were computationally predicted and subsequently assessed using
      transcriptional profiling. Pathway analysis demonstrated that the U-tAs
      associated miRNAs are involved in signaling pathways related to known health
      outcomes of iAs exposure including cancer and diabetes mellitus. Immune response
      related mRNAs were also identified with decreased expression levels associated
      with U-tAs, and predicted to be mediated in part by the arsenic-responsive
      miRNAs. Results of this study highlight miRNAs as novel responders to prenatal
      arsenic exposure that may contribute to associated immune response perturbations.

PMID- 24327381
TI  - Non-radial growth of helical homopolymer crystals: breaking the paradigm of the
      polymer spherulite microstructure.
AB  - Radial symmetry is essential for the conventional view of the polymer spherulite
      microstructure. Typically it is assumed that, in the course of the spherulite
      morphogenesis, the lamellar crystals grow radially. Using submicron X-ray
      diffraction, it is shown that in banded spherulites of poly(propylene adipate)
      the crystals have the shape of a helix with flat-on crystals winding around a
      virtual cylinder of about 6 um in diameter. The helix angle of 30 degrees 
      implies that the crystal growth direction is tilted away from the spherulite
      radius by this angle. The implications of the helical crystal shape contradict
      the paradigm of the spherulitic microstructure. The radial growth rate of such
      spherulites does not correspond to the crystal growth rate, but to the
      propagation rate of the virtual cylinder the ribbons wind around. 

PMID- 24327382
TI  - Ion transport through polyelectrolyte multilayers.
AB  - Polyelectrolyte multilayer (PEM) films and capsules loaded with ion-sensitive
      fluorophores can be used as ion-sensors for many applications including
      measurements of intracellular ion concentration. Previous studies have shown the
      influence of the PEM films/shells on the specific response of encapsulated ion
      sensitive fluorophores. PEM shells are considered as semipermeable barriers
      between the environment and the encapsulated fluorophores. Parameters such as the
      time response of the encapsulated sensor can be affected by the porosity and
      charge of the PEM shell. In this study, the time response of an encapsulated pH
      sensitive fluorophore towards pH changes in the surrounding environment is
      investigated. Furthermore, the conductance of PEM films for potassium ions is
      determined. 

PMID- 24327385
TI  - LAMA2 mutations in adult-onset muscular dystrophy with leukoencephalopathy.

PMID- 24327386
TI  - [On the article Kaireit T et al. "Smartphones now even smarter - possibility of
      using a "dose warner" "].

PMID- 24327387
TI  - Basophil Activation Test in the diagnosis and monitoring of mastocytosis patients
      with wasp venom allergy.
AB  - Background: There is need for an accurate diagnostic test in mastocytosis
      patients with wasp venom allergy (WVA) and monitoring of these patients during
      immunotherapy (IT). In this study, we aimed to evaluate sensitivity and
      specificity of the Basophil Activation Test (BAT) as a diagnostic and monitoring
      test in patients with mastocytosis and WVA. Methods: Seventeen patients with
      mastocytosis and WVA and 6 mastocytosis patients without WVA were included. BAT
      was performed before the start of IT (1st visit) and at 6 weeks (2nd visit) and 1
      year (3rd visit), after reaching the maintenance dose. Of 17 patients included,
      11 complerted the 3rd visit.In mastocytosis patients with WVA, dose-dependent
      wasp-venom induced upregulation of CD63 and CD203c expression on basophils was
      observed compared to mastocytosis patients without WVA. Serum specific IgE, IgG4
      and tryptase levels were measured in all patients. Results: BAT had a sensitivity
      of 87% and specificity of 100% in diagnosing WVA in mastocytosis patients.
      Basophil allergen threshold sensitivity with respect to CD63 and CD203c was
      significantly decreased in the second visit compared to the first visit and
      increased significantly in the third visit compared to the second visit. Specific
      IgE levels increased significantly in the 2nd visit compared to first and
      decreased significantly in the third visti compared to the second. Specific IgG4
      levels rose significantly in the 2nd visit compared to the 1st and on the 3rd
      visit compared to the 2nd . Tryptase levels did not change significantly during
      the study. Conclusions: BAT can represent a diagnostic test in allergic patients
      with mastocytosis and these patients are better to be monitored for a longer
      period during IT. (c) 2013 Clinical Cytometry Society.

PMID- 24327388
TI  - Magnetic navigation facilitates percutaneous coronary intervention for complex
      lesions.
AB  - BACKGROUND: We sought to determine the utility of a magnetic navigation system
      (MNS) in treating a variety of coronary artery lesions including those that could
      not be revascularized with standard percutaneous coronary intervention (PCI). MNS
      may add value in the treatment of tortuous arteries and bifurcation lesions;
      however its widespread adoption has lagged because of cost and a lack of clear
      advantage over conventional PCI. We performed a retrospective analysis to
      determine whether MNS improved procedural success for highly complex lesions.
      METHODS AND RESULTS: One hundred and forty-eight patients underwent treatment
      with MNS at Mayo Clinic, Rochester. Clinical data, angiographic and procedural
      characteristics, lesion crossing success and outcomes were reviewed. Overall 133
      patients underwent successful revascularization with 87% (143) of 164 lesions
      crossed using MNS alone. Another six lesions required a combination of MNS and
      conventional devices resulting in overall success of 91% (149/164). Eighteen
      complex lesions had previously failed PCI and 12 (67%) were successfully treated
      with MNS. Success after failed PCI was higher (88%) when a frequent user operated
      MNS, but occasional users also noted incremental success (30%). Twenty-five
      chronic total occlusions were included amongst these 164 lesions, with observed
      antegrade MNS lesion crossing rates of 78% for regular and 14% for occasional
      users. CONCLUSIONS: MNS is a useful adjunct to performance of PCI. This
      specialized technology has a clear learning curve and can facilitate treatment of
      highly complex lesions.

PMID- 24327390
TI  - Palladium-mediated oxidative carbonylation reactions for the synthesis of (11) C
      radiolabelled ureas.
AB  - Palladium(II)-mediated oxidative carbonylation reactions have been used to
      synthesize (11) C-radiolabelled ureas via the coupling of amines with [(11)
      C]carbon monoxide, in a one-pot process. Following trapping of (11) CO in a
      solution of copper(I) tris(3,5-dimethylpyrazolyl)borate, homocoupling reactions
      of primary aliphatic amines proceed in the presence of Pd(PPh3 )2 Cl2 to give the
      corresponding N,N-disubstituted [(11) C]ureas. Secondary amines do not produce
      the corresponding N,N,N,N-tetrasubsituted [(11) C]ureas under these conditions.
      This difference in reactivity allows for the formation of unsymmetrical N,N',N'
      trisubstituted [(11) C]ureas using a mixture of a primary amine and a reactive
      secondary amine. The potential use of this method in positron emission tomography
      (PET) was demonstrated by the synthesis of the M1 muscarinic acetylcholine
      receptor radiotracer, [(11) C-carbonyl]GSK1034702. 

PMID- 24327389
TI  - Racial/ethnic differences in clinical trial enrollment, refusal rates,
      ineligibility, and reasons for decline among patients at sites in the National
      Cancer Institute's Community Cancer Centers Program.
AB  - BACKGROUND: This study examined racial/ethnic differences among patients in
      clinical trial (CT) enrollment, refusal rates, ineligibility, and desire to
      participate in research within the National Cancer Institute's Community Cancer
      Centers Program (NCCCP) Clinical Trial Screening and Accrual Log. METHODS: Data
      from 4509 log entries were evaluated in this study. Four logistic regression
      models were run using physical/medical conditions, enrollment into a CT, patient
      eligible but declined a CT, and no desire to participate in research as dependent
      variables. RESULTS: Age >= 65 years (OR = 1.51, 95% CI = 1.28-1.79), males (OR =
      2.28, 95% CI = 1.92-2.71), and non-Hispanic black race (OR = 1.53, 95% CI = 1.2
      1.96) were significantly associated with more physical/medical conditions. Age >=
      65 years was significantly associated with lower CT enrollment (OR = 0.83, 95% CI
      = 0.7-0.98). Males (OR = 0.78, 95% CI = 0.65-0.94) and a higher grade level score
      for consent form readability (OR = 0.9, 95% CI = 0.83-0.97) were significantly
      associated with lower refusal rates. Consent page length >= 20 was significantly
      associated with lower odds of "no desire to participate in research" among CT
      decliners (OR = 0.75, 95% CI = 0.58-0.98). CONCLUSIONS: There were no
      racial/ethnic differences in CT enrollment, refusal rates, or "no desire to
      participate in research" as the reason given for CT refusal. Higher odds of
      physical/medical conditions were associated with older age, males, and non
      Hispanic blacks. Better management of physical/medical conditions before and
      during treatment may increase the pool of eligible patients for CTs. Future work
      should examine the role of comorbidities, sex, age, and consent form
      characteristics on CT participation.

PMID- 24327391
TI  - Seeking and Utilizing a Curandero in the United States: A Literature Review.
AB  - PURPOSE: The purpose of this systematic review was to address two key questions:
      "Why do Hispanics seek a curandero?" And "How do Hispanics utilize the
      curandero?" METHODS: The literature was reviewed using two databases-PubMed and
      CINAHL-during the period January 2000 to September 2012-and reference lists for
      potentially relevant studies. The search terms used were Hispanics/Latinos,
      curandero, CAM use, and traditional healers/medicine. Terms were searched in the
      keywords, title, and abstract. FINDINGS: Of the 30 articles reviewed, 9 reflected
      the two key questions. Hispanics seek curanderos because they are affordable and
      are Spanish literate. Less common reasons include immigration status, culturally
      appropriate, spiritual healing, acculturation, and dissatisfaction with Western
      medicine. Hispanics utilize curanderos for a range of illnesses, including folk
      illnesses and treatments that may be unfamiliar to health care practitioners.
      IMPLICATIONS: Utilization of a curandero among the U.S. Hispanics was the focus
      of only four nursing articles on the practice of curanderos, but these did not
      address nursing implications. Knowledge of Hispanic folk illnesses and treatments
      is important in providing culturally appropriate holistic care. Furthermore,
      patient disclosure about the use of curanderos and folk remedies given may be
      critical to Western medical providers and the treatments they give.

PMID- 24327392
TI  - Studies on enantioselective liquid-liquid extraction of amino-(4-nitro-phenyl)
      acetic acid enantiomers: modeling and optimization.
AB  - BINAP-metal complexes were prepared as extractant for enantioselective liquid
      liquid extraction (ELLE) of amino-(4-nitro-phenyl)-acetic acid (NPA) enantiomers.
      The influence of process variables, including types of organic solvents and metal
      precursor, concentration of ligand, pH, and temperature on the efficiency of the
      extraction, were investigated experimentally. An interfacial reaction model was
      established for insightful understanding of the chiral extraction process.
      Important parameters required for the model were determined. The experimental
      data were compared with model predictions to verify the model prediction, It was
      found that the interfacial reaction model predicted the experimental results
      accurately. By modeling and experiment, an optimal extraction condition with pH
      of 7 and host (extractant) concentration of 1 mmol/L was obtained and high
      enantioselectivity (alphaop ) of 3.86 and performance factor (pf) of 0.1949 were
      achieved.

PMID- 24327396
TI  - Rod-like nano-light harvester.
AB  - Imitating the natural "energy cascade" architecture, we present a single
      molecular rod-like nano-light harvester (NLH) based on a cylindrical polymer
      brush. Block copolymer side chains carrying (9,9-diethylfluoren-2-yl)methyl
      methacrylate units as light absorbing antennae (energy donors) are tethered to a
      linear polymer backbone containing 9-anthracenemethyl methacrylate units as
      emitting groups (energy acceptors). These NLHs exhibit very efficient energy
      absorption and transfer. Moreover, we manipulate the energy transfer by tuning
      the donor-acceptor distance. 

PMID- 24327397
TI  - Percutaneous balloon dilation of severe pulmonary valve stenosis in patients with
      cyanosis and congestive heart failure.
AB  - OBJECTIVES: This article reports outcomes of percutaneous balloon dilation in
      patients with severe pulmonary valve stenosis, in particular in those treated
      late with cyanosis, congestive heart failure, and pericardial effusion.
      BACKGROUND: Percutaneous balloon dilation is the treatment of choice for
      pulmonary valve stenosis. Although earlier intervention may produce better
      results, patients may present late with congestive heart failure and cyanosis.
      METHODS: Fifty-five patients who underwent pulmonary valve balloon dilation, were
      grouped into two groups, based on the presence or absence of congestive right
      heart failure and/or central cyanosis. Group I included 33 patients with severe
      pulmonary valve stenosis, but without clinical evidence of congestive right heart
      failure in the form of liver enlargement, raised jugular venous pressure, and
      peripheral edema and/or central cyanosis and group II included 22 patients with
      severe pulmonary valve stenosis and congestive right heart failure and/or central
      cyanosis. Their outcomes were compared. RESULTS: Doppler measured transvalvar
      pressure gradient decreased from 110.2 +/- 34.0 mm Hg before to 52.5 +/- 28.7 mm
      Hg in group I after dilation (P < 0.001), and from 138.4 +/- 32.3 mm Hg to 53.9
      +/- 19.3 mm Hg in group II, (P < 0.001). Complications included ventricular
      tachycardia/fibrillation in three patients and severe bradycardia in one patient
      in group II. Twelve patients in group II developed clinical and radiologic
      evidence of reperfusion injury/pulmonary edema within the first 24 hr of
      intervention and needed ventilation for 2-9 days. Three of these patients died
      from intractable pulmonary edema. On follow up, clinical and echocardiographic
      improvement parameters were similar in the two groups. CONCLUSION: Those patients
      with severe pulmonary valve stenosis with congestive right heart failure,
      especially those with pericardial effusion, ascites and cyanosis, represent an
      important technical and clinical challenge. They are a high-risk group with or
      without treatment. If they survive the procedure, they may still remain at a high
      risk in the first few days afterward. Maintaining their ventilator and inotropic
      support after balloon dilation may increase survival. However, excellent results
      can be obtained.

PMID- 24327399
TI  - Pharmacy legislation: public protector or professional hindrance?
AB  - Pharmacy originates from a background of medication compounding and supply. More
      recently, this role has developed away from an absolute focus on the supply of
      pharmaceuticals with, for example, the advent of pharmacist prescribing.
      Nevertheless, for a majority of the profession, medication supply remains a core
      activity. Regulation of the pharmacy profession is now the responsibility of the
      General Pharmaceutical Council, although up until 27 September 2010, this role
      fell to the Royal Pharmaceutical Society of Great Britain (RPSGB). Before this
      change, in one of the most high-profile legal cases involving a pharmacist in a
      professional capacity, R. v Lee, a pharmacist was prosecuted firstly for gross
      negligence manslaughter, later revised to offences under the Medicines Act 1968,
      for a single error relating to medication supply, and was given a suspended
      custodial sentence. Offences against sections 64 or 85 of the Medicines Act are
      absolute offences and there is no due diligence defence. Prosecution of a
      pharmacist for the supply of incorrect medication may seem a measured course of
      action to protect the public from the wrongful supply of potent
      pharmacotherapeutic agents; however, further analysis of Lee indicates that this
      approach may be counterproductive. An appeal of the original conviction in the
      Lee case has resulted in a clarification of the interpretation of section 85(5);
      however currently, prosecutions under section 64 are still a possibility. Owing
      to the seriousness of a criminal conviction under section 64, this continuation
      will potentially stifle the profession's ability to learn from dispensing errors.

PMID- 24327398
TI  - ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid
      cancer.
AB  - BACKGROUND: In their previous analysis of papillary thyroid carcinomas (PTCs)
      from an Ukrainian-American cohort that was exposed to iodine-131 ((131) I) from
      the Chernobyl accident, the authors identified RET/PTC rearrangements and other
      driver mutations in 60% of tumors. METHODS: In this study, the remaining mutation
      negative tumors from that cohort were analyzed using RNA sequencing (RNA-Seq) and
      reverse transcriptase-polymerase chain reaction to identify novel chromosomal
      rearrangements and to characterize their relation with radiation dose. RESULTS:
      The ETS variant gene 6 (ETV6)-neurotrophin receptor 3 (NTRK3) rearrangement (ETV6
      NTRK3) was identified by RNA-Seq in a tumor from a patient who received a high
      (131) I dose. Overall, the rearrangement was detected in 9 of 62 (14.5%) post
      Chernobyl PTCs and in 3 of 151 (2%) sporadic PTCs (P = .019). The most common
      fusion type was between exon 4 of ETV6 and exon 14 of NTRK3. The prevalence of
      ETV6-NTRK3 rearrangement in post-Chernobyl PTCs was associated with increasing
      (131) I dose, albeit at borderline significance (P = .126). The group of
      rearrangement-positive PTCs (ETV6-NTRK3, RET/PTC, PAX8-PPARgamma) was associated
      with significantly higher dose response compared with the group of PTCs with
      point mutations (BRAF, RAS; P < .001). In vitro exposure of human thyroid cells
      to 1 gray of (131) I and gamma-radiation resulted in the formation of ETV6-NTRK3
      rearrangement at a rate of 7.9 * 10(-6) cells and 3.0 * 10(-6) cells,
      respectively. CONCLUSIONS: The authors report the occurrence of ETV6-NTRK3
      rearrangements in thyroid cancer and demonstrate that this rearrangement is
      significantly more common in tumors associated with exposure to (131) I and has a
      borderline significant dose response. Moreover, ETV6-NTRK3 rearrangement can be
      directly induced in thyroid cells by ionizing radiation in vitro and, thus, may
      represent a novel mechanism of radiation-induced carcinogenesis.

PMID- 24327400
TI  - TiS2 and ZrS2 single- and double-wall nanotubes: first-principles study.
AB  - Hybrid density functional theory has been applied for investigations of the
      electronic and atomic structure of bulk phases, nanolayers, and nanotubes based
      on titanium and zirconium disulfides. Calculations have been performed on the
      basis of the localized atomic functions by means of the CRYSTAL-2009 computer
      code. The full optimization of all atomic positions in the regarded systems has
      been made to study the atomic relaxation and to determine the most favorable
      structures. The different layered and isotropic bulk phases have been considered
      as the possible precursors of the nanotubes. Calculations on single-walled TiS2
      and ZrS2 nanotubes confirmed that the nanotubes obtained by rolling up the
      hexagonal crystalline layers with octahedral 1T morphology are the most stable.
      The strain energy of TiS2 and ZrS2 nanotubes is small, does not depend on the
      tube chirality, and approximately obeys to D(-2) law (D is nanotube diameter) of
      the classical elasticity theory. It is greater than the strain energy of the
      similar TiO2 and ZrO2 nanotubes; however, the formation energy of the disulfide
      nanotubes is considerably less than the formation energy of the dioxide
      nanotubes. The distance and interaction energy between the single-wall components
      of the double-wall nanotubes is proved to be close to the distance and
      interaction energy between layers in the layered crystals. Analysis of the
      relaxed nanotube shape using radial coordinate of the metal atoms demonstrates a
      small but noticeable deviation from completely cylindrical cross-section of the
      external walls in the armchair-like double-wall nanotubes.

PMID- 24327401
TI  - Biocompatibility and tissue integration of a novel shape memory surgical mesh for
      ventral hernia: in vivo animal studies.
AB  - Approximately 400,000 ventral hernia repair surgeries are performed each year in
      the United States. Many of these procedures are performed using laparoscopic
      minimally invasive techniques and employ the use of surgical mesh. The use of
      surgical mesh has been shown to reduce recurrence rates compared to standard
      suture repairs. The placement of surgical mesh in a ventral hernia repair
      procedure can be challenging, and may even complicate the procedure. Others have
      attempted to provide commercial solutions to the problems of mesh placement, but
      these have not been well accepted by the clinical community. In this article, two
      versions of shape memory polymer (SMP)-modified surgical mesh, and unmodified
      surgical mesh, were compared by performing laparoscopic manipulation in an acute
      porcine model. Also, SMP-integrated polyester surgical meshes were implanted in
      four rats for 30-33 days to evaluate chronic biocompatibility and capacity for
      tissue integration. Porcine results show that the modified mesh provides a
      controlled, temperature-activated, automated deployment when compared to an
      unmodified mesh. In rats, results indicate that implanted SMP-modified meshes
      exhibit exceptional biocompatibility and excellent integration with surrounding
      tissue with no noticeable differences from the unmodified counterpart. This
      article provides further evidence that an SMP-modified surgical mesh promises
      reduction in surgical placement time and that such a mesh is not substantially
      different from unmodified meshes in chronic biocompatibility.

PMID- 24327402
TI  - Involving paediatricians-in-training in quality and service improvement.

PMID- 24327403
TI  - Hypothermia did not improve mortality or disability in severe traumatic brain
      injury.

PMID- 24327404
TI  - Development of an automated system for preparation of liquid scintillation
      counting samples for radiolabeled pharmaceuticals.
AB  - Radiolabeled compounds are essential tools in drug development used to obtain
      critical metabolism and safety information. To support the synthesis and ensure
      quality of radiolabeled compounds for all programs, bench automation has been
      implemented in our laboratories. The concept of a platform technology for bench
      top automation is not new. A considerable investment in the automation of various
      critical analytical laboratory workflows to both harmonize the efforts of a large
      and diverse global organization and minimize capital footprint has been made on
      our part. Various custom automation techniques and applications have been
      developed to increase capabilities and productivity of radiochemical analyses at
      Merck. In this paper, we will present a novel system that is capable of
      automating the liquid scintillation counting procedure. The system has handled
      multiple radiolabeled ((3)H, (14)C, and (35)S) pharmaceutical compounds with an
      accuracy of 5% with a standard deviation of 2% and a cycle time of ~10 min per
      analysis.

PMID- 24327405
TI  - Strong intermolecular exciton couplings in solid-state circular dichroism of aryl
      benzyl sulfoxides.
AB  - A series of 13 enantiopure aryl benzyl sulfoxides () with different substituents
      on the two aromatic rings has been previously analyzed by means of electronic
      circular dichroism (CD) spectroscopy. Most of these compounds are crystalline and
      their X-ray structure is established. For almost one-half of the series, CD
      spectra measured in the solid state were quite different from those in
      acetonitrile solution. We demonstrate that the difference is due to strong
      exciton couplings between molecules packed closely together in the crystal. The
      computational approach consists of time-dependent density functional theory
      (TDDFT) calculations run on "dimers" composed of nearest neighbors found in the
      lattice. Solid-state CD spectra are well reproduced by the average of all
      possible pairwise terms. The relation between the crystal space group and
      conformation, and the appearance of solid-state CD spectra, is also discussed.

PMID- 24327407
TI  - Anatomy and biomechanics of the elbow joint.
AB  - Magnetic resonance (MR) imaging provides clinically useful information in
      assessing the elbow joint. Superior depiction of muscles, ligaments and tendons
      as well as the ability to directly visualize nerves, bone marrow and hyaline
      cartilage, are advantages of MR imaging relative to conventional imaging
      techniques. As the elbow is located superficially, clinical examination is easier
      for the orthopedic surgeon and only a few cases need a diagnosis for the
      radiologist, for this reason the elbow joint is little known for the radiologist.
      To better understand the injuries that occur in the elbow during the sport
      activities, we need a better understanding of the biomechanics of the joint. And
      for understanding the biomechanics, it is necessary to know the exact anatomy of
      the elbow joint and to be able to identify each anatomic structure in the
      different imaging planes and pulse sequences. This is especially important in MR
      as the imaging tool that shows a highest soft tissue resolution among other
      imaging techniques. 

PMID- 24327406
TI  - LEAP: highly accurate prediction of protein loop conformations by integrating
      coarse-grained sampling and optimized energy scores with all-atom refinement of
      backbone and side chains.
AB  - Prediction of protein loop conformations without any prior knowledge (ab initio
      prediction) is an unsolved problem. Its solution will significantly impact
      protein homology and template-based modeling as well as ab initio protein
      structure prediction. Here, we developed a coarse-grained, optimized scoring
      function for initial sampling and ranking of loop decoys. The resulting decoys
      are then further optimized in backbone and side-chain conformations and ranked by
      all-atom energy scoring functions. The final integrated technique called loop
      prediction by energy-assisted protocol achieved a median value of 2.1 A root mean
      square deviation (RMSD) for 325 12-residue test loops and 2.0 A RMSD for 45 12
      residue loops from critical assessment of structure-prediction techniques (CASP)
      10 target proteins with native core structures (backbone and side chains). If all
      side-chain conformations in protein cores were predicted in the absence of the
      target loop, loop-prediction accuracy only reduces slightly (0.2 A difference in
      RMSD for 12-residue loops in the CASP target proteins). The accuracy obtained is
      about 1 A RMSD or more improvement over other methods we tested. The executable
      file for a Linux system is freely available for academic users at http://sparks
      lab.org.

PMID- 24327408
TI  - The value of multislice computed tomography in the diagnosis of elbow fractures.
AB  - Within the sports pathology it is vital the functional recovery of the lesions.
      To achieve this goal it is necessary very precise anatomical information. The
      elbow region is made up of three bones that together they have a complex
      relationship. Range of motion is wide and is thanks to the form of their
      components. To obtain precise information we need complex imaging techniques that
      allow us to avoid overlaps that show conventional radiology. Thanks to the
      development of CT multislices we have a high precision tool. Following the
      classification of the AO Foundation describes all types of fracture and provides
      images with 3D reconstruciton which allows you to schedule surgery the surgeon
      with a degree of prior information that approximates the excellence. 

PMID- 24327409
TI  - Osteochondral lesions of the elbow.
AB  - Osteochondral lesions of the elbow are injuries that disrupt the cartilage and
      subjacent bone, and they most commonly involve the capitellum. The staging,
      prognosis, and treatment of osteochondral lesions in the elbow are based on a
      combination of radiographic, magnetic resonance imaging, and arthroscopic
      findings. Radiographic staging includes the radiolucent, separation, and free
      (advanced) stages. MR imaging features of instability include cysts,
      osteochondral fracture, T2 hyperintense rim, subchondral plate defects, and fluid
      filled osteochondral defects. Finally, arthroscopic grading of osteochondral
      lesions increases in severity based on findings of softened cartilage, cartilage
      fissuring, exposed bone, loose but nondisplaced fragments, and eventually
      displaced fragments resulting in intra-articular bodies. This pictorial review
      focuses on osteochondral lesions in the capitellum and trochlea including
      osteochondritis dissecans, Panner disease, and acute trauma. 

PMID- 24327410
TI  - Imaging of sports ligamentous injuries of the elbow.
AB  - Ligamentous injuries of the elbow are common in sports. The diagnosis is usually
      based on a combination of the assessment of the mechanism of injury during the
      sporting activity and physical examination. Imaging with radiographs and MR
      imaging has an important diagnostic role, particularly when the clinical
      presentation is unclear and to evaluate for other important potential associated
      injuries such as myotendinous injuries, fractures, dislocations, and
      osteochondral lesions. Treatment includes conservative and surgical measures
      depending on the severity of the instability and associated injuries. We provide
      a detailed review of sports-related injuries of the medial and lateral collateral
      ligament complexes of the elbow with an emphasis on imaging manifestations of
      disease and a discussion of the anatomy, biomechanics, and treatment options. 

PMID- 24327411
TI  - Imaging finger joint instability with ultrasound.
AB  - Closed injuries affecting the metacarpophalangeal and interphalangeal joints and
      their stabilizers in the thumb and fingers occur very commonly in athletes,
      possibly leading to finger joint instability and long-standing or permanent
      disability. This article reviews the spectrum of joint injuries of the thumb and
      fingers that are common in the athletic population with a main focus on the
      ultrasound features of collateral ligament tears, palmar plate injuries, and
      thumb sesamoid fractures. A thorough understanding of the complex anatomy,
      mechanism of injury, soft tissue abnormalities, and imaging findings is critical
      in the diagnostic work-up of closed finger joint trauma and may help improve
      outcomes. 

PMID- 24327412
TI  - Synthetic niches for differentiation of human embryonic stem cells bypassing
      embryoid body formation.
AB  - The unique self-renewal and pluripotency features of human embryonic stem cells
      (hESCs) offer the potential for unlimited development of novel cell therapies.
      Currently, hESCs are cultured and differentiated using methods, such as monolayer
      culture and embryoid body (EB) formation. As such, achieving efficient
      differentiation into higher order structures remains a challenge, as well as
      maintaining cell viability during differentiation into homogeneous cell
      populations. Here, we describe the application of highly porous polymer scaffolds
      as synthetic stem cell niches. Bypassing the EB formation step, these scaffolds
      are capable of three-dimensional culture of undifferentiated hESCs and subsequent
      directed differentiation into three primary germ layers. H9 hESCs were
      successfully maintained and proliferated in biodegradable polymer scaffolds based
      on poly (lactic-co-glycolic acid) (PLGA). The results showed that cells within
      PLGA scaffolds retained characteristics of undifferentiated pluripotent stem
      cells. Moreover, the scaffolds allowed differentiation towards the lineage of
      interest by the addition of growth factors to the culture system. The in vivo
      transplantation study revealed that the scaffolds could provide a
      microenvironment that enabled hESCs to interact with their surroundings, thereby
      promoting cell differentiation. Therefore, this approach, which provides a unique
      culture/differentiation system for hESCs, will find its utility in various stem
      cell-based tissue-engineering applications.

PMID- 24327417
TI  - Materials and optimized designs for human-machine interfaces via epidermal
      electronics.
AB  - Thin, soft, and elastic electronics with physical properties well matched to the
      epidermis can be conformally and robustly integrated with the skin. Materials and
      optimized designs for such devices are presented for surface electromyography
      (sEMG). The findings enable sEMG from wide ranging areas of the body. The
      measurements have quality sufficient for advanced forms of human-machine
      interface. 

PMID- 24327420
TI  - Alternative approaches for PET radiotracer development in Alzheimer's disease:
      imaging beyond plaque.
AB  - Alzheimer's disease (AD) and related dementias show increasing clinical
      prevalence, yet our understanding of the etiology and pathobiology of disease
      related neurodegeneration remains limited. In this regard, noninvasive imaging
      with radiotracers for positron emission tomography (PET) presents a unique tool
      for quantifying spatial and temporal changes in characteristic biological markers
      of brain disease and for assessing potential drug efficacy. PET radiotracers
      targeting different protein markers are being developed to address questions
      pertaining to the molecular and/or genetic heterogeneity of AD and related
      dementias. For example, radiotracers including [(11) C]-PiB and [(18) F]-AV-45
      (Florbetapir) are being used to measure the density of Abeta-plaques in AD
      patients and to interrogate the biological mechanisms of disease initiation and
      progression. Our focus is on the development of novel PET imaging agents,
      targeting proteins beyond Abeta-plaques, which can be used to investigate the
      broader mechanism of AD pathogenesis. Here, we present the chemical basis of
      various radiotracers which show promise in preclinical or clinical studies for
      use in evaluating the phenotypic or biochemical characteristics of AD.
      Radiotracers for PET imaging neuroinflammation, metal ion association with Abeta
      plaques, tau protein, cholinergic and cannabinoid receptors, and enzymes
      including glycogen-synthase kinase-3beta and monoamine oxidase B amongst others,
      and their connection to AD are highlighted.

PMID- 24327421
TI  - Clinical outcomes in real-world patients with small vessel disease treated with
      XIENCE V(r) everolimus-eluting stents: one year results from the XIENCE V(r) USA
      condition of approval post-market study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the 1-year clinical
      outcomes of more complex XIENCE V USA real-world patients with small versus
      nonsmall vessel lesions. BACKGROUND: Patients with small vessel lesions
      undergoing coronary stent placement are at higher risk of major adverse cardiac
      events. Improved safety and efficacy of XIENCE V everolimus eluting stents (EES)
      have been previously demonstrated in selected low-risk small vessel populations
      in randomized clinical trials. METHODS: The XIENCE V USA study was a condition of
      approval, single-arm study in unselected real-world patients. Baseline and 1-year
      clinical outcomes were compared between XIENCE V USA patients who received a
      single 2.5 mm stent (small vessel group, N = 838) and patients implanted with a
      single >2.5 mm stent (non-small vessel group, N = 2,015). Mean reference vessel
      diameter was 2.55 +/- 0.36 and 3.25 +/- 0.46 mm in the small and non-small vessel
      groups, respectively (P < 0.001). RESULTS: Small vessel group had more females,
      presented with a higher rate of diabetes, and had more complex lesion
      characteristics. The definite or probable ST rates analyzed using Kaplan-Meier
      method were low and not significantly different between the groups at 0.37 and
      0.40% for the small and nonsmall vessel group (P = 0.88), respectively. The
      composite rate of cardiac death or MI was comparable at 4.5% for the small and
      5.1% for the non-small vessel 1 groups (P = 0.57). The 1-year target lesion
      revascularization rate was also comparable in the small vessel group (3.8% vs.
      3.0%, P = 0.35). CONCLUSIONS: Despite gender difference, higher prevalence of
      diabetes and more complex lesions in the small vessel groups, the 1-year clinical
      outcomes were similar in both small and nonsmall vessel groups. These results
      demonstrate the therapeutic benefit of XIENCE V EES in a real-world all inclusive
      patient population with small vessel disease.

PMID- 24327422
TI  - Effect of a randomized controlled trial on the surgical treatment of spinal
      metastasis, 2000 through 2010: a population-based cohort study.
AB  - BACKGROUND: The effect of randomized controlled trials (RCT) on clinical practice
      patterns and patient outcomes is understudied. A 2005 RCT by Patchell et al
      demonstrated benefit for surgical decompression in patients with spinal
      metastasis (SpM). We examined trends in spinal surgery for patients with SpM
      before and after publication of the Patchell RCT. METHODS: The Nationwide
      Inpatient Sample (NIS) was used to identify a 20% stratified sample of surgical
      SpM admissions to nonfederal United States hospitals from 2000 to 2004 and 2006
      to 2010, excluding 2005 when the RCT was published. Propensity scores were
      generated and logistic regression analysis was performed to compare outcomes in
      pre- and post-RCT time periods. RESULTS: A total of 7404 surgical admissions were
      identified. The rate of spine surgery increased post-RCT from an average of 3.8%
      to 4.9% surgeries per metastatic admission per year (P = .03). Admissions in the
      post-RCT group were more likely to be non-Caucasian, lower income, Medicaid
      recipients, and have more medical comorbidities and a greater metastatic burden
      (P < .001). Logistic regression of the propensity-matched sample showed increased
      odds post-RCT for expensive hospital stay (2.9; 95% confidence interval [CI] =
      2.6-3.4) and some complications, including neurologic (1.7; 95% CI = 1.1-2.8),
      venous thromboembolism (2.8; 95% CI = 1.9-4.2), and decubitis ulcers (15.4; 95%
      CI = 6.7-34.5). However, odds for in-hospital mortality decreased (0.6; 95% CI =
      0.5-0.8). CONCLUSIONS: Surgery for SpM increased after publication of a positive
      RCT. A significantly greater proportion of patients with lower socioeconomic
      status, more comorbidities, and greater metastatic burden underwent surgery post
      RCT. These patients experienced more postoperative complications and higher in
      hospital charges but less in-hospital mortality.

PMID- 24327423
TI  - Proteomic analysis and polyamines, ethylene and reactive oxygen species levels of
      Araucaria angustifolia (Brazilian pine) embryogenic cultures with different
      embryogenic potential.
AB  - Somatic embryogenesis is an important biotechnological tool in the large-scale
      propagation of elite genotypes and ex situ conservation of conifer species.
      Protocols for the induction and proliferation of embryogenic cultures (ECs) of
      Brazilian pine (Araucaria angustifolia (Bert.) O. Ktze) are well established,
      although the proper formation of mature somatic embryos (SEs) is still
      problematic. Thus, the identification of molecular markers for the screening of
      ECs able to respond to maturation conditions (abscisic acid and osmotic agents)
      is highly desirable. To develop molecular markers for the early detection of ECs
      able to develop well-formed SEs under maturation conditions, we analyzed the
      proteins found during the proliferation phase of A. angustifolia cell lines with
      different embryogenic capabilities, with one cell line being responsive to
      maturation conditions (R cell line), and one cell line that presented blocked
      development of SEs (B cell line). In addition, based on the peptides identified,
      polyamine levels (free and conjugate), ethylene production and reactive oxygen
      species (ROS) emission were analyzed using both EC lines (R and B cell lines). A
      marked difference in the biochemistry of ECs between these two cell lines was
      observed. Eleven proteins that were differentially expressed in the cell lines
      were identified by the combination of two-dimensional electrophoresis (2-DE) and
      MALDI-TOF/TOF mass spectrometry. Among these, S-adenosylmethionine synthase, the
      enzyme associated with polyamines and ethylene biosynthesis, was observed
      exclusively in the R cell line, while a protein linked to the oxidative stress
      subunit F of NADH dehydrogenase was observed exclusively in the B cell lines.
      Additionally, B cell lines showed higher levels of diamine putrescine and lower
      levels of ethylene. Higher values of ethylene and ROS were observed for the cell
      line that showed normal development of SEs. Altogether, our results open new
      perspectives in the optimization of culture conditions for A. angustifolia
      somatic embryogenesis, as well as establishing biochemical markers for the early
      selection of ECs during maturation trials. 

PMID- 24327425
TI  - Arabidopsis thaliana and Pisum sativum models demonstrate that root colonization
      is an intrinsic trait of Burkholderia cepacia complex bacteria.
AB  - Burkholderia cepacia complex (Bcc) bacteria possess biotechnologically useful
      properties that contrast with their opportunistic pathogenicity. The rhizosphere
      fitness of Bcc bacteria is central to their biocontrol and bioremediation
      activities. However, it is not known whether this differs between species or
      between environmental and clinical strains. We investigated the ability of 26 Bcc
      strains representing nine different species to colonize the roots of Arabidopsis
      thaliana and Pisum sativum (pea). Viable counts, scanning electron microscopy and
      bioluminescence imaging were used to assess root colonization, with Bcc bacteria
      achieving mean (+/-sem) levels of 2.49+/-0.23*10(6) and 5.16+/-1.87*10(6) c.f.u.
      per centimetre of root on the A. thaliana and P. sativum models, respectively.
      The A. thaliana rhizocompetence model was able to reveal loss of colonization
      phenotypes in Burkholderia vietnamiensis G4 transposon mutants that had only
      previously been observed in competition experiments on the P. sativum model.
      Different Bcc species colonized each plant model at different rates, and no
      statistical difference in root colonization was observed between isolates of
      clinical or environmental origin. Loss of the virulence-associated third
      chromosomal replicon (>1 Mb DNA) did not alter Bcc root colonization on A.
      thaliana. In summary, Bcc bacteria possess intrinsic root colonization abilities
      irrespective of their species or source. As Bcc rhizocompetence does not require
      their third chromosomal replicon, the possibility of using synthetic biology
      approaches to engineer virulence-attenuated biotechnological strains is
      tractable. 

PMID- 24327424
TI  - Epstein-Barr virus antibody titer and its association with the domain scores from
      the World Health Organization's Quality of Life questionnaire: Findings from
      Rural Hainan Province, China.
AB  - OBJECTIVE: Epstein-Barr virus (EBV) antibody titer has recently been used as a
      biomarker of psychological stress. This is the first study to investigate the
      association between EBV antibody titer and perceived quality of life (QOL) in
      Hainan Island, China. METHODS: Participants from two regions of Hainan Island,
      recruited into a larger study investigating the health impact of rapid economic
      development among rural residents, were stratified by age, sex, and region; 15
      people were randomly selected from each of the 16 subgroups, to give a total
      sample size of 240. EBV antibody titer in dried blood spot samples was measured
      by enzyme-linked immunosorbent assay. The abbreviated version of the World Health
      Organization's Quality of Life questionnaire was used to gather information on
      six categories of QOL. Multiple linear regression analysis was used to examine
      the relationship between EBV antibody titer and QOL. RESULTS: After adjusting for
      the effects of age, sex, region and C-reactive protein concentration, EBV
      antibody titer was negatively associated with the physical (P = 0.044) and
      psychological QOL domains (P = 0.039). CONCLUSION: This study suggests that among
      individuals living in an environment in the initial stages of economic
      development EBV antibody titer, a biomarker of psychological stress, is not only
      associated with the psychological aspects of QOL but is also linked to physical
      problems.

PMID- 24327426
TI  - Comment on "Clinical application of massively parallel sequencing-based prenatal
      non-invasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies
      with mixed risk factors".

PMID- 24327427
TI  - Response to "concerns about the statistical methodology described in the
      'clinical application of massively parallel sequencing-based prenatal noninvasive
      fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk
      factors'".

PMID- 24327428
TI  - Comment on "is fetal magnetic resonance imaging indicated when ultrasound
      isolated mild ventriculomegaly is present in pregnancies with no risk factors?".

PMID- 24327429
TI  - Comment on "first trimester uterine artery Doppler velocimetry in the prediction
      of birth weight in a low-risk population".

PMID- 24327430
TI  - Comment on "prenatal diagnosis and prognosis in Noonan syndrome".

PMID- 24327431
TI  - Comment on "what is predictive of preterm delivery in the first trimester:
      isthmus or cervical length?".

PMID- 24327432
TI  - Tuning optical conductivity of large-scale CVD graphene by strain engineering.
AB  - A controllable optical anisotropy in CVD graphene is shown. The transparency in
      the visible range of pre-strained CVD graphene exhibits a periodic modulation as
      a function of polarization direction. The strain sensitivity of the optical
      response of graphene demonstrated here can be effectively utilized towards novel
      ultra-thin optical devices and strain sensing applications. 

PMID- 24327433
TI  - Catheter approach to redirect hepatic venous return for treatment of unilateral
      pulmonary arteriovenous malformations after fontan.
AB  - OBJECTIVES: The goal of this report is to describe a percutaneous approach to
      rerouting hepatic venous return in patients who developed progressive cyanosis
      due to unilateral pulmonary arteriovenous malformations (PAVM) after the total
      cavopulmonary connection (TCPC) operation. BACKGROUND: Unilateral PAVM can
      develop in patients after TCPC operation when there is unequal distribution of
      hepatic venous return between the two lungs. This often results in progressive
      cyanosis and the need for surgical re-intervention. A percutaneous based approach
      for rerouting hepatic venous return has never been described. METHODS: We
      retrospectively reviewed the clinical data on four patients who underwent
      percutaneous rerouting procedures. One patient with a misaligned TCPC underwent
      realignment of the circuit with a bare metal stent. In three patients a
      combination of bare metal and covered stents were needed to achieve the desired
      results. RESULTS: The rerouting procedures were successful in all patients with
      significant improvement in oxygen saturation from a median of 75% (range 55-80%)
      to a median of 90% (range 84-92%) (P = 0.02). There were no recorded short term
      or intermediate term complications with maximum follow-up time of 43 months.
      CONCLUSIONS: Percutaneous rerouting of hepatic venous flow is feasible and should
      be considered when a surgical approach is not possible; this strategy may serve
      as a viable alternative to complex operative approaches in select cases.
      Furthermore studies are needed to determine the long-term efficacy of this
      procedure.

PMID- 24327435
TI  - Radiolabeled antagonistic bombesin peptidomimetics for tumor targeting.
AB  - The replacement of amide bonds in the backbone of peptides by proteolytically
      stable 1,2,3-triazole isosteres can provide novel peptidomimetics with promising
      properties for the development of tumor-targeting radiopeptides. On the basis of
      our previous work with radiolabeled agonistic bombesin (BBN) derivatives of the
      sequence [Nle(14) ]BBN(7-14), we substituted selected amide bonds of the
      structurally closely related antagonistic peptide analog JMV594. With the
      exception of the C-terminal modification, amide-to-triazole substitutions
      tolerated by [Nle(14) ]BBN(7-14) without loss of biological function led to
      abolished receptor affinity in the case of JMV594. These findings provide an
      additional piece of evidence for the currently disputed differences in the modes
      of action of agonistic and antagonistic gastrin-releasing peptide receptor (GRPR)
      targeting radiopeptides.

PMID- 24327434
TI  - Progress in the management of limited-stage small cell lung cancer.
AB  - Approximately 15% of lung cancer cases are of the small cell subtype, but this
      variant is highly aggressive and is often diagnosed at advanced stages. Outcomes
      after current treatment regimens have been poor, with 5-year survival rates as
      low as 25% for patients with limited-stage disease. Advances in therapy for small
      cell lung cancer have included the development of more effective chemotherapeutic
      agents and radiation techniques. For example, hyperfractionated radiotherapy
      given early in the course of the disease can reduce local recurrence and extend
      survival. Other technologic advances in radiation planning and delivery such as
      intensity-modulated radiotherapy, image-guided adaptive radiotherapy, and 4
      dimensional computed tomography/positron emission tomography have facilitated the
      design of treatment volumes that closely conform to the shape of the tumor, which
      allows higher radiation doses to be given while minimizing radiation-induced
      toxicity to adjacent structures. Future improvements in outcomes will require
      clarifying the molecular basis for this disease.

PMID- 24327436
TI  - Syntheses, receptor bindings, in vitro and in vivo stabilities and
      biodistributions of DOTA-neurotensin(8-13) derivatives containing beta-amino acid
      residues - a lesson about the importance of animal experiments.
AB  - Neurotensin(8-13) (NTS(8-13)) analogs with C- and/or N-terminal beta-amino acid
      residues and three DOTA derivatives thereof have been synthesized (i.e., 1-6). A
      virtual docking experiment showed almost perfect fit of one of the 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives, 6a, into a
      crystallographically identified receptor NTSR1 (Fig.1). The affinities for the
      receptors of the NTS analogs and derivatives are low, when determined with cell
      membrane homogenates, while, with NTSR1-exhibiting cancer tissues, affinities in
      the single-digit nanomolar range can be observed (Table 2). Most of the beta
      amino acid-containing NTS(8-13) analogs (Table 1 and Fig.2), including the (68)
      Ga complexes of the DOTA-substituted ones (6; Figs.2 and 5), are stable for ca. 1
      h in human serum and plasma, and in murine plasma. The biodistributions of two
      (68) Ga complexes (of 6a and 6b) in HT29 tumor-bearing nude mice, in the absence
      and in the presence of a blocking compound, after 10, 30, and 60 min (Figs. 3 and
      4) lead to the conclusion that the amount of specifically bound radioligand is
      rather low. This was confirmed by PET-imaging experiments with the tumor-bearing
      mice (Fig.6). Comparison of the in vitro plasma stability (after 1 h) with the ex
      vivo blood content (after 10-15 min) of the two (68) Ga complexes shows that they
      are rapidly cleaved in the animals (Fig.5).

PMID- 24327437
TI  - Sebaceous lipid profiling of bat integumentary tissues: quantitative analysis of
      free Fatty acids, monoacylglycerides, squalene, and sterols.
AB  - White-nose syndrome (WNS) is a fungal disease caused by Pseudogymnoascus
      destructans and is devastating North American bat populations. Sebaceous lipids
      secreted from host integumentary tissues are implicated in the initial attachment
      and recognition of host tissues by pathogenic fungi. We are interested in
      determining if ratios of lipid classes in sebum can be used as biomarkers to
      diagnose severity of fungal infection in bats. To first establish lipid
      compositions in bats, we isolated secreted and integral lipid fractions from the
      hair and wing tissues of three species: big brown bats (Eptesicus fuscus),
      Eastern red bats (Lasiurus borealis), and evening bats (Nycticeius humeralis).
      Sterols, FFAs, MAGs, and squalene were derivatized as trimethylsilyl esters,
      separated by gas chromatography, and identified by mass spectrometry. Ratios of
      sterol to squalene in different tissues were determined, and cholesterol as a
      disease biomarker was assessed. Free sterol was the dominant lipid class of bat
      integument. Squalene/sterol ratio is highest in wing sebum. Secreted wing lipid
      contained higher proportions of saturated FFAs and MAGs than integral wing or
      secreted hair lipid. These compounds are targets for investigating responses of
      P. destructans to specific host lipid compounds and as biomarkers to diagnose
      WNS. 

PMID- 24327438
TI  - Chemical constituents and biological activities of pinus species.

PMID- 24327439
TI  - Terpenes from the soft corals of the genus Sarcophyton: chemistry and biological
      activities.
AB  - This review covers structural diversity and biological activities of terpenes
      from soft corals of the genus of Sarcophyton, reported from 1995 to July, 2011.
      During this period, besides undefined species, 16 species of the genus
      Sarcophyton, from different geographical areas, had been chemically examined. Two
      hundred and five terpenes had been isolated from this genus, including eleven
      sesquiterpenes, 165 diterpenes, 29 biscembranoids, some of which had novel
      skeletons. They exhibited various biological features, such as antifeedant, anti
      inflammatory, antiviral, and antifouling activities. 

PMID- 24327440
TI  - 5alpha-Androst-16-en-3alpha-ol beta-D-glucuronide, precursor of 5alpha-androst-16
      en-3alpha-ol in human sweat.
AB  - 5alpha-Androst-16-en-3alpha-ol (alpha-androstenol) is an important contributor to
      human axilla sweat odor. It is assumed that alpha-andostenol is excreted from the
      apocrine glands via a H2 O-soluble conjugate, and this precursor was formally
      characterized in this study for the first time in human sweat. The possible H2 O
      soluble precursors, sulfate and glucuronide derivatives, were synthesized as
      analytical standards, i.e., alpha-androstenol, beta-androstenol sulfates, 5alpha
      androsta-5,16-dien-3beta-ol (beta-androstadienol) sulfate, alpha-androstenol beta
      glucuronide, alpha-androstenol alpha-glucuronide, beta-androstadienol beta
      glucuronide, and alpha-androstenol beta-glucuronide furanose. The occurrence of
      alpha-androstenol beta-glucuronide was established by ultra performance liquid
      chromatography (UPLC)/MS (heated electrospray ionization (HESI)) in negative-ion
      mode in pooled human sweat, containing eccrine and apocrine secretions and
      collected from 25 female and 24 male underarms. Its concentration was of 79 ng/ml
      in female secretions and 241 ng/ml in male secretions. The release of alpha
      androstenol was observed after incubation of the sterile human sweat or alpha
      androstenol beta-glucuronide with a commercial glucuronidase enzyme, the urine
      isolated bacteria Streptococcus agalactiae, and the skin bacteria Staphylococcus
      warneri DSM 20316, Staphylococcus haemolyticus DSM 20263, and Propionibacterium
      acnes ATCC 6919, reported to have beta-glucuronidase activities. We demonstrated
      that if alpha- and beta-androstenols and androstadienol sulfates were present in
      human sweat, their concentrations would be too low to be considered as potential
      precursors of malodors; therefore, the H2 O-soluble precursor of alpha
      androstenol in apocrine secretion should be a beta-glucuronide.

PMID- 24327441
TI  - Mitsunobu reactions of 5-fluorouridine with the terpenols phytol and nerol: DNA
      building blocks for a biomimetic lipophilization of nucleic acids.
AB  - The cancerostatic 5-fluorouridine (5-FUrd; 1) was sequentially sugar-protected by
      introduction of a 2',3'-O-heptylidene ketal group (->2), followed by 5'-O
      monomethoxytritylation (->3). This fully protected derivative was submitted to
      Mitsunobu reactions with either phytol ((Z and E)-isomer) or nerol ((Z)-isomer)
      to yield the nucleoterpenes 4a and 4b. Both were 5'-O-deprotected with 2% Cl2
      CHCOOH in CH2 Cl2 to yield compounds 5a and 5b, respectively. These were
      converted to the 5'-O-cyanoethyl phosphoramidites 6a and 6b, respectively.
      Moreover, the 2',3'-O-(1-nonyldecylidene) derivative, 7a, of 5-fluorouridine was
      resynthesized and labelled at C(5') with an Eterneon-480 fluorophor((r)) (->7b).
      The resulting nucleolipid was studied with respect to its incorporation in an
      artificial bilayer, as well as to its aggregate formation. Additionally, two
      oligonucleotides carrying terminal phytol-alkylated 5-fluorouridine tags were
      prepared, one of which was studied concerning its incorporation in an artificial
      lipid bilayer. 

PMID- 24327442
TI  - The creation of proton hopping from a drug-receptor encounter.
AB  - We extend recent modeling studies of proton hopping, used to describe the
      functioning of membrane channels and axon nerve conduction, to offer an
      explanation of the initiation of the nerve impulse at an effector-ligand
      encounter. This encounter is proposed to create a hydronium ion in the vicinity
      of the effector and ligand, which leads to a continuous flow of protons, called
      proton hopping, through water adjacent to this encounter. This proton hopping is
      proposed to be the message carried from the encounter to the axon of a particular
      nerve system associated with that particular effector-ligand system.

PMID- 24327443
TI  - Chemosystematic analyses of Gingidia volatiles.
AB  - The leave volatiles of six Gingidia species from New Zealand and Australia and
      the seed volatiles of G. grisea were characterized by solid-phase microextraction
      (SPME)-GC/MS analysis. This technique, using a small quantity of samples and
      automated extraction, gave repeatable results, with maximum sensitivity for
      medium volatility compounds. The major monoterpenes among the volatiles, i.e.,
      beta-phellandrene (4), limonene (6), and gamma-terpinene (5), and
      phenylpropanoids, i.e., estragole (3), (E)-anethole (7), and myristicin (1),
      showed to be useful chemotaxonomic markers. For G. grisea leaves and seeds,
      similar compositions were detected, characterized by high contents of 4. As
      leaves were more readily available for study than seeds, they were used for
      further investigations. The G. grisea leaf volatiles showed infraspecific
      variation in the ratio of 4/5 between and within sites of collection. The G.
      montana leaf volatiles also showed infraspecific variation, with high contents of
      3 at one site and high contents of 7 at another. The SPME-GC/MS analysis of G.
      montana herbarium voucher specimens resulted in the identification of further
      chemotypes for this species. The volatiles of the G. amphistoma samples were all
      dominated by 7 and those of the G. haematitica samples were rich in 5. Moreover,
      single plants of two Australian Gingidia species were analyzed; the volatiles of
      G. harveyana showed high concentrations of 5 and 7, whereas those of G. rupicola
      were dominated by 5 and 1. 

PMID- 24327444
TI  - Synthesis of 5-fluorouridine nucleolipid derivatives and their
      cytostatic/cytotoxic activities on human HT-29 colon carcinoma cells.
AB  - One of the major drawbacks of chemotherapeutics is their insufficient penetration
      through cell membranes due to a high hydrophobicity. Thus, we have synthesized a
      series of selected nucleolipid derivatives of 5-fluorouridine (5-FUrd; 2a),
      carrying lipophilic moieties at N(3) and/or in the 2',3'-O-position (i.e., 3a-7a
      and 3c), and tested their cytostatic/cytotoxic activities using HT-29 human colon
      carcinoma cells, in comparison with, e.g., 5-FU (1) and 5-FUrd (2a).
      Incorporation and intracellular localization of the substances under test were
      performed after conjugation with the fluorochrome Atto 425. We showed that all 5'
      O-labelled Atto 425 derivatives were incorporated by the human HT-29 cells and
      accumulated in their cytoplasm. Moreover, after 24-h treatment of HT-29 human
      colon carcinoma cells, 1 or 2a (10, 20, 40, or 80 MUM) revealed a significant (14
      23 or 33-45%, resp.) decrease of the viability in comparison with the (negative)
      control. Interestingly, derivatives 3a and 3c (40 and 80 MUM) led to a
      significant (77-95 or 89-96%, resp.) inhibition of survival of human HT29 cells,
      i.e., these two substances were ca. 63-72% or ca. 75%, respectively more
      effective than 5-FU (1; positive control). Furthermore, derivative 5a showed a
      significant, i.e., 30 and 86%, inhibition of the survival at 40 and 80 MUM,
      respectively in comparison with the (negative) control. Some synthesized 5-FUrd
      derivatives turned out to be more effective than 5-FU (1) or 5-FUrd (2a). 

PMID- 24327445
TI  - An interactive SAR approach to discover novel hybrid thieno probes as ligands for
      D2-like receptors with affinities in the subnanomolar range.
AB  - A series of [(phenylpiperazinyl)alkyl]-isoindole-1,3-dione derivatives was
      synthesized to serve as probes for dopaminergic receptors. Among this series,
      compound 6a showed the highest affinity towards D4 and D3 receptors with Ki
      values in the low nanomolar range, and D2/D4- and D2/D3-selectivity indices of 72
      and 20, respectively. Optimization rounds were adopted and led to the D4
      selective ligand thiophene-2-carboxamide 9a with a Ki (D4) value of 0.62 nM, and
      to its butyl analog, 10a, with Ki (D4) and Ki (D3) values of 0.03 and 0.26 nM,
      respectively. Docking experiments revealed the importance of the unique D4
      residue Arg186 in manipulating the ligands' D4-subtype-receptor selectivity.

PMID- 24327446
TI  - Synthesis, characterization, and anti-amoebic activity of N-(pyrimidin-2
      yl)benzenesulfonamide derivatives.
AB  - A new series of N-(pyrimidin-2-yl)benzenesulfonamide derivatives, 3a-3i and 4a
      4i, was synthesized from pyrimidin-2-amines, 2a-2i, with the aim to explore their
      effects on in vitro growth of Entamoeba histolytica. The chemical structures of
      the compounds were elucidated by elemental analysis, FT-IR, (1) H- and (13) C
      NMR, and ESI mass-spectral data. In vitro anti-amoebic activity was evaluated
      against HM1 : IMSS strain of Entamoeba histolytica. The IC50 values were
      calculated by using the double dilution method. The results were compared with
      the IC50 value of the standard drug 'metronidazole'. The selected compounds were
      tested for their cytotoxic activities by cell-viability assay using H9C2 cardiac
      myoblasts cell line, and the results indicated that all the compounds displayed
      remarkable >80% viabilities to a concentration of 100 MUg/ml.

PMID- 24327447
TI  - Variation of the chemical composition and antimicrobial activity of the essential
      oils of natural populations of Tunisian Daucus carota L. (Apiaceae).
AB  - The essential oils of Daucus carota L. (Apiaceae) seeds sampled from ten wild
      populations spread over northern Tunisia were characterized by GC-FID and GC/MS
      analyses. In total, 36 compounds were identified in the D. carota seed essential
      oils, with a predominance of sesquiterpene hydrocarbons in most samples (22.63
      89.93% of the total oil composition). The main volatile compounds identified were
      beta-bisabolene (mean content of 39.33%), sabinene (8.53%), geranyl acetate
      (7.12%), and elemicin (6.26%). The volatile composition varied significantly
      across the populations, even for oils of populations harvested in similar areas.
      The chemometric principal component analysis and the hierarchical clustering
      identified four groups, each corresponding to a composition-specific chemotype.
      The in vitro antimicrobial activity of the isolated essential oils was
      preliminarily evaluated, using the disk-diffusion method, against one Gram
      positive (Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli
      and Salmonella typhimurium), as well as against a pathogenic yeast (Candida
      albicans). All tested essential oils exhibited interesting antibacterial and
      antifungal activities against the assayed microorganisms. 

PMID- 24327448
TI  - Enzymatic modification of palmarosa essential oil: chemical analysis and
      olfactory evaluation of acylated products.
AB  - We have developed an enzymatic protocol to modify the composition of palmarosa
      essential oil by acylation of its alcohol components by three different acyl
      donors at various rates. The resulting modified products were characterized by
      qualitative and quantitative analyses by gas chromatography, and their olfactory
      properties were evaluated by professional perfumers. We showed that our protocol
      resulted in two types of modifications of the olfactory properties. The first and
      most obvious effect observed was the decrease of the alcohol content, with the
      concomitant increase of the corresponding esters, along with their fruity notes
      (pear, most notably). The second and less obvious effect was the expression of
      notes from minor components ((E)-beta-ocimene, linalool, beta-caryophyllene, and
      farnesene), originally masked by the sweet-floral-rose odor of geraniol, present
      in 70% in the palmarosa essential oil used, and emergence of citrus, green, spicy
      and clove characters in the modified products. This methodology might be
      considered in the future as a sustainable route to new natural ingredients for
      the perfumer. 

PMID- 24327450
TI  - Differences in the neurochemical and behavioural profiles of lisdexamfetamine
      methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis
      and locomotor activity measurements in freely-moving rats.
AB  - Lisdexamfetamine dimesylate is a novel prodrug approved in North America, Europe
      and Brazil for treating attention deficit hyperactivity disorder (ADHD). It
      undergoes rate-limited hydrolysis by red blood cells to yield d-amphetamine.
      Following our previous work comparing lisdexamfetamine with d-amphetamine, the
      neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and
      modafinil were compared by dual-probe microdialysis in the prefrontal cortex
      (PFC) and striatum of conscious rats with simultaneous locomotor activity
      measurement. We employed pharmacologically equivalent doses of all compounds and
      those that spanned the therapeutically relevant and psychostimulant range.
      Lisdexamfetamine (0.5, 1.5, 4.5 mg/kg d-amphetamine base, per os (po)),
      methylphenidate (3, 10, 30 mg/kg base, po) and modafinil (100, 300, 600 mg/kg
      base, po) increased efflux of dopamine and noradrenaline in PFC, and dopamine in
      striatum. Only lisdexamfetamine increased 5-hydroxytryptamine (5-HT) efflux in
      PFC and striatum. Lisdexamfetamine had larger and more sustained effects on
      catecholaminergic neurotransmission than methylphenidate or modafinil. Linear
      correlations were observed between striatal dopamine efflux and locomotor
      activity for lisdexamfetamine and methylphenidate, but not modafinil. Regression
      slopes revealed greater increases in extracellular dopamine could be elicited
      without producing locomotor activation by lisdexamfetamine than methylphenidate.
      These results are consistent with clinical findings showing that lisdexamfetamine
      is an effective ADHD medication with prolonged duration of action and good
      separation between its therapeutic actions and stimulant side-effects. 

PMID- 24327451
TI  - Evidence for a crucial modulating role of the sodium channel in the QTc
      prolongation related to antipsychotics.
AB  - Blockade of the cardiac hERG channel is recognized as the main mechanism
      underlying the QT prolongation induced by many classes of drugs, including
      antipsychotics. However, antipsychotics interact with a variety of other
      pharmacological targets that could also modulate cardiac function. The present
      study aims to identify those key factors involved in the QT prolongation induced
      by antipsychotics. The interactions of 28 antipsychotics were measured on a
      variety of pharmacological targets. Binding affinity (K(i)), functional channel
      blockade (IC50), and the corresponding ratios to total and free plasma drug
      concentration were compared with the corrected QT changes (QTc) associated with
      the therapeutic use of these drugs by multivariable linear regression analysis to
      determine the best predictors of QTc. Besides confirming hERG as the primary
      predictor of QTc, all analyses consistently show the concomitant involvement of
      Na(V)1.5 channel as modulating factor of the QTc related to hERG blockade. In
      particular, the hERG/Na(V)1.5 ratio explains the 57% of the overall QTc
      variability associated with antipsychotics. Since it is known that inhibition of
      late I Na could offset the dysfunctional effects of hERG blockade, we hypothesize
      the inhibition of late I(Na) as a crucial compensatory mechanism of the QTc
      associated with antipsychotics and hence an important factor to consider
      concomitantly with hERG blockade to appraise the arrhythmogenic risk of these
      drugs more accurately.

PMID- 24327453
TI  - Acute disseminated encephalomyelitis presenting with hypertensive emergency.
AB  - We report a 12-year-old girl presenting with acute disseminated encephalomyelitis
      (ADEM) along with hypertensive emergency. Hypertension persisted for few weeks
      following recovery and subsided with oral clonidine. Although autonomic
      instability in ADEM has been reported before, hypertensive emergency was not
      previously documented as presenting feature of ADEM. 

PMID- 24327452
TI  - Psychiatric profiles of mothers who take Ecstasy/MDMA during pregnancy: reduced
      depression 1 year after giving birth and quitting Ecstasy.
AB  - BACKGROUND: The recreational drug MDMA (3,4-methylenedioxymethamphetamine) or
      'Ecstasy' is associated with heightened psychiatric distress and feelings of
      depression. The Drugs and Infancy Study (DAISY) monitored the psychiatric symptom
      profiles of mothers who used Ecstasy/MDMA while pregnant, and followed them over
      the first year post-partum. METHODS: We compared 28 young women whom took MDMA
      during their pregnancy with a polydrug control group of 68 women who took other
      psychoactive drugs while pregnant. The Brief Symptom Inventory (BSI) was
      completed for several periods: The first trimester of pregnancy; and 1, 4 and 12
      months after childbirth. Recreational drug use was monitored at each time point.
      RESULTS: During the first trimester of pregnancy, MDMA-using mothers reported
      higher depression scores than the polydrug controls. At 1 year after childbirth,
      their BSI depression scores were significantly lower, now closer to the control
      group values. At the same time point, their self-reported use of MDMA became
      nearly zero, in contrast to their continued use of Cannabis/marijuana, nicotine
      and alcohol. We found significant symptom reductions in those with BSI obsessive
      compulsive and interpersonal sensitivity, following Ecstasy/MDMA cessation.
      CONCLUSIONS: The findings from this unique prospective study of young
      recreational drug-using mothers are consistent with previous reports of improved
      psychiatric health after quitting MDMA.

PMID- 24327454
TI  - Evaluating clinical course of BCG lymphadenitis and factors affect on it during a
      5-year period in Kerman, Iran.
AB  - INTRODUCTION: One of the preventive methods of pulmonary tuberculosis is bacillus
      Calmette-Guerin (BCG) vaccination and one of the common complications of vaccine
      is lymphadenitis. We aimed to evaluate clinical course of BCG lymphadenitis in
      children of Kerman Province, Iran. METHOD: 314 children with BCG lymphadenitis
      were enrolled in study. Patients were followed up monthly regarding clinical
      improvement and complications. RESULTS: BCG lymphadenitis was improved in many
      patients during follow up; during 6 months 23.7% of patients had spontaneous
      regression. Only the primary size of lymphadenitis had significant effect on
      clinical course of lymphadenitis and developing complication (p = 0.0540).
      CONCLUSION: Many patients improved without any intervention. The primary size of
      lymphadenitis may affect clinical course of lymphadenitis and dispose person to
      abscess and fistula. To confirm this result and evaluate efficiency of preventive
      surgery instead of observation further study is recommended.

PMID- 24327455
TI  - Pedicled no-touch saphenous vein graft harvest limits vascular smooth muscle cell
      activation: the PATENT saphenous vein graft study.
AB  - OBJECTIVE: Neointimal hyperplasia secondary to vascular smooth muscle cell (VSMC)
      activation limits the long-term patency of saphenous vein grafts (SVGs). We
      compared markers of vascular injury and VSMC activation in SVGs harvested using
      the pedicled 'no-touch' (NT) vs the conventional (CON) technique. METHODS:
      Patients undergoing coronary artery bypass surgery were enrolled in the PATENT
      SVG trial (clinicaltrials.gov NCT01488084). Patients were randomly allocated to
      have SVGs harvested with the NT technique from one leg and the CON method from
      the other. SVG segments underwent morphometry, histological and electron
      microscopy assessments and transcript measurements of VSMC activation and
      differentiation markers. Leg wound functional recovery and harvest site
      complications were assessed using a quality-of-life questionnaire. RESULTS: A
      total of 17 patients (65.3 +/- 7.3 years) were enrolled. SVGs harvested using the
      NT vs CON technique exhibited preserved intimal, medial and adventitial
      architecture. CON harvest was associated with greater medial Kruppel-like factor
      4 transcript levels (0.26 +/- 0.05 vs 0.11 +/- 0.02, P < 0.05). CON samples had
      significantly lower medial serum response factor (0.53 +/- 0.11 vs 1.44 +/- 0.50,
      P < 0.05) and myocardin (0.59 +/- 0.08 vs 1.33 +/- 0.33, P < 0.05) transcript
      levels. MicroRNA-145, an inhibitor of VSMC activation and differentiation, was
      higher in the NT vs CON samples (1.84 +/- 1.03 vs 0.50 +/- 0.19, P < 0.05). Leg
      assessment scores were worse in the NT legs at 3 months, but similar to CON
      scores at 12 months. CONCLUSIONS: SVGs harvested using the 'NT' technique exhibit
      an early molecular and morphological pattern consistent with decreased VSMC
      activation compared with CON harvesting. Functional leg recovery was similar in
      both groups at 12 months. Larger studies are required to corroborate these
      findings.

PMID- 24327456
TI  - Oesophageal foreign body in the left main bronchus.

PMID- 24327457
TI  - Herniation of an abdominal antireflux fundoplication into the chest: what does it
      mean?
AB  - OBJECTIVES: The specific contribution of the herniation of an abdominal
      antireflux fundoplication into the chest to symptomatic and therefore surgical
      failure remains unclear. METHODS: The study was conducted in 189 consecutive
      fundoplication patients, categorized as patients reoperated on for chest
      herniation of either an abdominal 360 degrees  (Group 1; n = 95) or a partial
      (Group 2; n = 10) fundoplication, and patients having undergone an intrathoracic
      360 degrees  fundoplication for short oesophagus (Group 3; n = 84; reference
      group). There were four subgroups in Group 1: 1A: wrap still complete and
      perioesophageal; 1B: wrap still complete but perigastric; 1C: wrap still
      perioesophageal but partially disrupted and 1D: wrap perigastric and partially
      disrupted. RESULTS: The prevalence of defective symptoms (heartburn and
      regurgitation) was significantly lower (P < 0.0001) in Group 3 (0.0%) and
      Subgroup 1A (3.7%) than in Subgroups 1B (84.4%), 1C (86.7%) and 1D (100%) and
      Group 2 (100%). The prevalence of obstructive symptoms (dysphagia, chest pain,
      necrosis and perforation) was significantly higher (P < 0.0001) in Subgroup 1A
      (100%) than in Subgroups 1B (57.8%), 1C (60.0%) and 1D (25.0%). The prevalence of
      a short oesophagus, an abdominal wall hernia repair and high abdominal pressure
      episodes in reoperated patients were 13.7, 36.2 and 67.2%, respectively.
      CONCLUSIONS: Unlike perigastric or partial fundoplication, a 360 degrees 
      perioesophageal abdominal fundoplication, when herniated into the chest, is still
      effective against reflux. Obstructive symptoms are due to either diaphragmatic
      strangulation or perigastric migration of the wrap (slipknot effect). Short
      oesophagus, weakness of the abdominal wall and high abdominal pressure episodes
      favour the herniation process.

PMID- 24327458
TI  - One-step two-dimensional microfluidics-based synthesis of three-dimensional
      particles.
AB  - Synthesis of three-dimensional anisotropic microparticles using a simple one-step
      microfluidic-based method is described. The method exploits the nonuniformity of
      the polymerizing UV light, UV absorption by opaque nanoparticles in the precursor
      solution, and discontinuous photomask patterns to make magnetic and non-magnetic
      microparticles in a twodimensional microchannel. Numerical simulations of monomer
      conversion in the microfluidic channel are performed to predict the manufactured
      particle shape. 

PMID- 24327459
TI  - Diagnostic utility of central node necrosis in predicting extracapsular spread
      among oral cavity squamous cell carcinoma.
AB  - BACKGROUND: Oral cavity squamous cell carcinoma (SCC) represents the most common
      SCC affecting the head and neck region. Long-term survival of patients with oral
      cavity SCC is adversely affected by lymph node metastasis and further decreased
      by the presence of lymph node extracapsular spread (ECS). METHODS: Using a case
      control design, preoperative CT scans from patients with oral cavity SCC and
      metastatic lymphadenopathy were evaluated by 2 independent neuroradiologists,
      blinded to the study, for a number of radiologic parameters, including central
      node necrosis. Multivariate logistic regression was used to identify parameters
      independently predicting pathologic ECS. RESULTS: For both neuroradiologists,
      central node necrosis was a significant predictor of ECS, with high interrater
      agreement (kappa = 0.71). On multivariate analysis, only central node necrosis
      independently predicted ECS (odds ratio [OR] = 12.1; 95% confidence interval [CI]
      = 1.24-119). Central node necrosis predicted ECS with 91% sensitivity and 88%
      negative predictive values. CONCLUSION: Our findings suggest that central node
      necrosis on preoperative CT scans is strongly associated with the presence of
      ECS.

PMID- 24327460
TI  - 18F-Fluorodeoxyglycosylamines: Maillard reaction of 18F-fluorodeoxyglucose with
      biological amines.
AB  - The Maillard reaction of sugars and amines resulting in the formation of
      glycosylamines and Amadori products is of biological significance, for drug
      delivery, role in central nervous system, and other potential applications. We
      have examined the interaction of (18) F-fluorodeoxyglucose ((18) F-FDG) with
      biological amines to study the formation of (18) F-fluorodeoxyglycosylamines
      ((18) F-FDGly). Respective amines N-allyl-2-aminomethylpyrrolidine (NAP) and 2
      (4'-aminophenyl)-6-hydroxybenzothiazole (PIB precursor) were mixed with FDG to
      provide glycosylamines, FDGNAP and FDGBTA. Radiosynthesis using (18) F-FDG (2-5
      mCi) was carried out to provide (18) F-FDGNAP and (18) F-FDGBTA. Binding of
      FDGBTA and (18) F-FDGBTA was evaluated in human brain sections of Alzheimer's
      disease (AD) patients and control subjects using autoradiography. Both FDGNAP and
      FDGBTA were isolated as stable products. Kinetics of (18) F-FDGNAP reaction
      indicated a significant product at 4 h (63% radiochemical yield). (18) F-FDGBTA
      was prepared in 57% yield. Preliminary studies of FDGBTA showed displacement of
      (3) H-PIB (reduced by 80%), and (18) F-FDGBTA indicated selective binding to
      Abeta-amyloid plaques present in postmortem AD human brain, with a gray matter
      ratio of 3 between the AD patients and control subjects. We have demonstrated
      that (18) F-FDG couples with amines under mild conditions to form (18) F-FDGly in
      a manner similar to click chemistry. Although these amine derivatives are stable
      in vitro, stability in vivo and selective binding is under investigation.

PMID- 24327461
TI  - Glycosylated platycosides: identification by enzymatic hydrolysis and structural
      determination by LC-MS/MS.
AB  - In this study, enzymatic hydrolysis and chemometric methods were utilized to
      discriminate glycosylated platycosides in the extract of Platycodi Radix by LC
      MS. Laminarinase, whose enzymatic activity was evaluated using gentiobiose and
      laminaritriose, was a suitable enzyme to identify the glycosylated platycosides.
      The laminarinase produced deapi-platycodin D and platycodin D from the isolated
      deapi-platycoside E and platycoside E through the loss of two glucose units by
      enzymatic reaction, respectively. After hydrolyzing a crude extract by
      laminarinase, the reconstructed total ion chromatogram generated by a chemometric
      technique sorted peaks of deglycosylated platycosides easily. Structural
      information of the glycosylated isomers was revealed through fragment ions
      generated by the sodiated C0beta ion corresponding to reduced disaccharides in
      the positive MS(4) spectra. Characteristic fragment ions of Glc-(1->6)-Glc
      moieties were observed through ring cleavages of (0,2)A0beta, (0,3)A0beta, and
      (0,4)A0beta, whereas Glc-(1->3)-Glc moieties produced only (0,3)A0beta ions.
      Lithium-adducted platycosides allowed more detailed structural analysis of
      glycosidic bond cleavage corresponding to Y1beta and B1beta in addition to ring
      cleavage.

PMID- 24327462
TI  - Safety of percutaneous left atrial appendage closure with the Amplatzer cardiac
      plug in patients with atrial fibrillation and contraindications to
      anticoagulation.
AB  - OBJECTIVE: To evaluate the safety of percutaneous left atrial appendage (LAA)
      closure with the Amplatzer Cardiac Plug (ACP) in patients with nonvalvular atrial
      fibrillation (AF) who are not eligible for oral anticoagulation with warfarin.
      BACKGROUND: Anticoagulation is the treatment of choice for prevention of strokes
      in patients with AF, but some patients have contraindications to anticoagulation.
      METHODS: A total of 60 patients with a CHA2 DS2 -VASc score of at least 1 and
      contraindications to warfarin who underwent percutaneous LAA closure with the ACP
      were included. Stroke risk assessment was performed with the CHADS2 and CHA2 DS2 
      VASc score and the bleeding risk was calculated with the HAS-BLED-score. Follow
      up included office visits, telephone inquiries, and mail contact. RESULTS: Mean
      CHADS2 -, CHA2 DS2 -VASc-, and HAS-BLED scores were 2.6 (+/- 1.4), 4.3 (+/- 1.7),
      and 3.3 (+/- 1.0), respectively. Twenty-five percent had a history of previous
      bleeding without oral anticoagulation and 63.3% while receiving oral
      anticoagulation. In 36.7% other contraindications to warfarin were present.
      Procedural success was achieved in 95%. Mean follow-up time was 1.8 (1.0-2.8)
      years. The estimated annual stroke risk based on the CHADS2 -score was 5.8%. The
      estimated annual bleeding risk on warfarin based on the HAS-BLED score was 3.7%.
      During follow-up, the annual incidence of stroke was 0%. Major bleeding
      complications occurred in 1.9% annually. CONCLUSIONS: Percutaneous LAA closure
      with the ACP in patients with contraindications to oral anticoagulation is safe.
      The stroke and bleeding risk after percutaneous LAA closure is lower than
      predicted by conventional risk scores.

PMID- 24327463
TI  - Bias correction of risk estimates in vaccine safety studies with rare adverse
      events using a self-controlled case series design.
AB  - The self-controlled case series (SCCS) method is often used to examine the
      temporal association between vaccination and adverse events using only data from
      patients who experienced such events. Conditional Poisson regression models are
      used to estimate incidence rate ratios, and these models perform well with large
      or medium-sized case samples. However, in some vaccine safety studies, the
      adverse events studied are rare and the maximum likelihood estimates may be
      biased. Several bias correction methods have been examined in case-control
      studies using conditional logistic regression, but none of these methods have
      been evaluated in studies using the SCCS design. In this study, we used
      simulations to evaluate 2 bias correction approaches-the Firth penalized maximum
      likelihood method and Cordeiro and McCullagh's bias reduction after maximum
      likelihood estimation-with small sample sizes in studies using the SCCS design.
      The simulations showed that the bias under the SCCS design with a small number of
      cases can be large and is also sensitive to a short risk period. The Firth
      correction method provides finite and less biased estimates than the maximum
      likelihood method and Cordeiro and McCullagh's method. However, limitations still
      exist when the risk period in the SCCS design is short relative to the entire
      observation period. 

PMID- 24327465
TI  - Three-dimensional carbon nanotube sponge-array architectures with high energy
      dissipation.
AB  - Carbon nanotube sponges and aligned arrays are seamlessly integrated into
      numerous possible configurations such as series, parallel, package, and sandwich
      complex structures, leading to significantly broadened stress plateau and
      enhanced energy dissipation. 

PMID- 24327466
TI  - Oncologic results of the surgical salvage of recurrent laryngeal squamous cell
      carcinoma in a multicentric retrospective series: emerging role of supracricoid
      partial laryngectomy.
AB  - BACKGROUND: Several studies in the last decade evaluated conservative surgical
      procedures and, in particular, supracricoid operations as an alternative to total
      laryngectomy for the salvage of recurrences of laryngeal squamous cell carcinoma
      (SCC) after a first attempt of organ preservation. METHODS: The clinical records
      of 68 consecutive patients primarily treated by irradiation or endoscopic surgery
      and surgically salvaged by total laryngectomy or supracricoid partial
      laryngectomy in 2 large university hospitals in Italy from 2004 to 2010 were
      reviewed. RESULTS: The survival was not affected by the primary treatment or by
      salvage modality. The only parameter always keeping a prognostic value is the
      involvement of resection margins of salvage surgery. Patients with early relapse
      seem to have a worse prognosis than patients with a delayed relapse (p = .05 at
      Cox multivariate analysis and p = .048 at Wilcoxon test for overall survival [OS]
      from the primary treatment). CONCLUSION: Supracricoid operations, if the
      indications are careful, can prove reliable salvage procedures.

PMID- 24327467
TI  - Unusual Nodular Regenerative Hyperplasia Mimicking Liver Metastases in CEUS.

PMID- 24327468
TI  - Effect of aging and diffuse chronic pancreatitis on pancreas elasticity evaluated
      using semiquantitative EUS elastography.
AB  - PURPOSE: Endosonographic elastography has been introduced as a method of
      estimating the stiffness of pancreatic tumors. This prospective single-center
      study was conducted to evaluate changes in the stiffness of the pancreas related
      to age and diffuse chronic pancreatitis. PATIENTS AND METHODS: 46 individuals
      each up to age 60 (group 1) and over age 60 (group 2) with healthy pancreata and
      26 patients with diffuse chronic pancreatitis (group 3) were included. Three
      elastograms were obtained in each case by endosonography in a defined section
      through the pancreatic body. Elastograms were further evaluated by histogram
      analysis. Mean strain values, based on a range from 0 (hardest) to 255 (softest),
      and their standard deviation were calculated from the histogram. The three groups
      were compared statistically with regard to pancreatic stiffness. A cut-off level
      for the diagnosis of chronic pancreatitis was defined by testing receiver
      operating characteristics curves. RESULTS: The strain values (mean, SD) measured
      in the pancreatic body in groups 1 - 3 were 110.2 (23.9), 80.0 (16.4), and 32.4
      (11.9), respectively. Pairwise comparison of the groups revealed highly
      significant differences (p < 0.001). At a cut-off value of 50, the area under the
      curve was 0.993 for distinguishing between chronic pancreatitis and healthy
      pancreata in people aged over 60. CONCLUSION: Semiquantitative elastography shows
      that pancreata become significantly harder during aging, but remain softer than
      in chronic pancreatitis. A cut-off value of 50 is suggested as a possible
      diagnostic criterion for diffuse chronic pancreatitis.

PMID- 24327469
TI  - Correlation between cardiac tissue Doppler and peripheral vascular Doppler in the
      anemic fetus - an additional method to determine the transfusion threshold?
AB  - PURPOSE: To examine the relationship between cardiac tissue Doppler and
      peripheral vascular Doppler measurements in fetal anemia. MATERIALS AND METHODS:
      We analyzed high frame rate cardiac Tissue Doppler Imaging (TDI) data files of 26
      anemic fetuses. The peak systolic tissue velocity (PSV), peak systolic
      displacement (PD), and peak systolic strain (PS) were determined in the mid
      segment of the ventricular walls (ROI 1 right ventricle (RV), ROI 2 left
      ventricle (LV)) and in the basal segment of the ventricular walls (ROI 3
      tricuspid annulus, ROI 4 mitral annulus). TDI parameters were correlated with
      established fetal vascular Doppler parameters (peak systolic blood flow velocity
      (Vmax) in the middle cerebral artery (MCA), pulsatility index (PI) in the MCA, in
      the umbilical artery (UA), and in the venous duct (DV)). RESULTS: The PSV in the
      LV correlated significantly negatively with the PI in the MCA. Both the PSV and
      PD in the LV correlated significantly negatively with the PI in the UA. The PS in
      the RV correlated significantly negatively with the PI in the UA. The left
      ventricular PSV and PD correlated significantly positively with the PI in the DV.
      The Vmax in the MCA did not correlate with any systolic myocardial TDI parameter.
      CONCLUSION: In fetal anemia, peak systolic myocardial TDI parameters correlate
      with vascular Doppler parameters, confirming that TDI is a promising method to
      evaluate myocardial function in the anemic fetus. This suggests combining both
      techniques to quantify fetal myocardial function in anemia even more accurately,
      possibly allowing for the determination of the indication for intrauterine
      transfusion.

PMID- 24327470
TI  - Post-operative 3-dimensional contrast-enhanced ultrasound (CEUS) versus Tc99m
      DTPA in the detection of post-surgical perfusion defects in kidney transplants -
      preliminary findings.
AB  - PURPOSE: 2800 renal transplants are carried out annually in the UK and it is
      standard practice to perform a Tc-DTPA renogram examination after surgery to
      check perfusion. This provides some functional information but suffers from low
      spatial resolution, is lengthy, immobile and costly and uses ionizing radiation.
      We surmised that contrast-enhanced ultrasound (CEUS) would provide an accurate
      alternative with increased speed, resolution (temporal and spatial), cost
      efficiency and safety. MATERIALS AND METHODS: 97 renal transplant patients
      underwent both Tc-DTPA and CEUS after surgery to assess the perfusion of the
      graft. Tc-DTPA was performed in the nuclear medicine department with at least 10
      minutes of continuous screening and a standard dose of 150 mBq Tc-DTPA. CEUS
      consisted of I. V. 2.4 ml Sonovue contrast agent, 60 seconds continuous capture
      and a 3 D acquisition of the organ. 3 D CEUS was assessed using QLab analysis
      software. RESULTS: Tc-DTPA detected 9 perfusion defects of varying size. CEUS
      detected all these defects plus 14 further defects (0.2 - 17 % of total renal
      volume) not detected on DTPA. These results demonstrate a statistically
      significant divergence (p < 0.0001). Retrospective clinical correlation showed
      ligated polar arteries in 8 of these 14 cases. CONCLUSION: CEUS will detect
      perfusion defects seen with Tc-DTPA and due to increased spatial and temporal
      resolution and multiple scanning angles, will detect further perfusion defects
      not seen on Tc-DTPA. 3 D CEUS is useful in the quantification of perfusion
      defects. CEUS is an accurate examination for detecting renal transplant perfusion
      defects and will detect significantly more defects than DTPA.

PMID- 24327471
TI  - Correlation of contrast-enhanced ultrasound with two distinct types of blood
      vessels for the assessment of angiogenesis in lewis lung carcinoma.
AB  - OBJECTIVE: The aim of our study was to evaluate tumor angiogenesis in Lewis lung
      carcinoma (LLC) of mice using a contrast-enhanced ultrasound (CEUS) examination,
      and to determine the correlation of contrast-enhanced ultrasonographic parameters
      with different blood vessel markers of microvessel density (MVD). MATERIALS AND
      METHODS: Subcutaneous Lewis lung carcinomas were established in 25 mice, which
      were evaluated by contrast-enhanced US using SonoVue (a second-generation US
      contrast agent). The results were recorded as digital video images and the time
      intensity curves and hemodynamic parameters were analyzed. Pathological tumor
      specimens were obtained just after US examination. Tumor specimens were stained
      with hematoxylin and eosin (H & E) and expression of CD31 and CD34, the different
      endothelial cell markers, was determined by immunohistochemical straining. Then
      the relationship between the CEUS parameters and the level of MVD was analyzed.
      RESULTS: Two distinct types of microvessels were identified in Lewis lung
      carcinoma: differentiated (CD34 +) and undifferentiated (CD31 +) vessels. A
      significant correlation was found between CEUS parameters and undifferentiated
      MVD (CD31 + vessels) in LLC (P < 0.05). There was a reverse correlation between
      the different MVDs. CONCLUSION: The study showed that among the distinct types of
      vasculature (CD31 + and CD34 +) in Lewis lung carcinoma, the former correlated
      with the CEUS parameters. Therefore, CEUS using a second-generation US contrast
      agent may be useful for the evaluation of tumor angiogenesis of LLC of mice.

PMID- 24327472
TI  - [Transperineal ultrasound to measure cervical length of pregnant women in general
      and in particular with cervical insufficiency - a comparison of transabdominal
      and transperineal ultrasound as alternatives to transvaginal ultrasound].
AB  - PURPOSE: To investigate the feasibility of measuring cervical length by
      transabdominal and transperineal ultrasound as alternatives to transvaginal
      ultrasound. MATERIALS AND METHODS: 33 pregnant women with and 28 without cervical
      insufficiency at 16 to 35 weeks of gestation were examined by an experienced
      examiner (DEGUM II) and the cervical length was measured twice at an interval of
      6 months. Comparability, reliability and comfort of the patients during the
      examinations were taken for statistical analysis. RESULTS: There is poor
      agreement between transabdominal and transvaginal ultrasound (Lin's rho = 0.578),
      whereas transperineal ultrasound shows high correlation (Lin's rho = 0.922) to
      the measurements obtained transvaginally, a preference referring to the comfort
      scale and good reliability (ICC = 0.949). When regarding sub-groups (pregnant
      women with and without cervical insufficiency), transperineal ultrasound shows
      better results than transabdominal ultrasound. However, small cohort sizes affect
      the statistical validity. CONCLUSION: Transabdominal ultrasound cannot be
      recommended to measure cervical length. Besides providing exact measurements,
      transperineal ultrasound avoids contact between the cervix and the probe, is
      better accepted by patients and offers a simplified examination. This method is a
      good alternative to transvaginal ultrasound. Due to minor inaccuracies of the
      method, we recommend this technique only for patients with a cervix longer than
      2.5 cm. For further analysis concerning patients with cervical insufficiency,
      large-scale studies should be performed.

PMID- 24327473
TI  - Ultrasound elastography of pulmonary lesions - a feasibility study.
AB  - INTRODUCTION: The potential of sonography in the examination of lung tissue is
      extremely limited by the air-filled alveoles of the lung. Only in special
      circumstances like pleural adhesion lesions, atelectasis or pneumonia can lung
      tissue be visualized by B-mode sonography. Real-time elastography was primarily
      applied to detect and visualize pulmonary lesions. METHODS AND PATIENTS: 8
      patients with a total of 18 histologically proven metastases of the lung were
      included. All pulmonary lesions were detected by computed tomography. Sonographic
      examination was performed with a 7.5 MHz linear transducer (Acuson Antares
      premium edition, Siemens, Erlangen, Germany), including B-mode and real-time
      elastography (RTE). The mean distance between pleura and the lesions ranged from
      0 to 2.5 cm. Two lesions were located in the upper right lobe, eleven lesions in
      the lower right and five in the lower left lobe. RESULTS: RTE was able to detect
      and visualize all 18 pulmonary lesions in contrast to B-mode. The size and
      distance of the lesions from the pleura correlated with the CT findings.
      CONCLUSION: In contrast to B-mode sonography, RTE is able to detect and visualize
      peripheral, non-pleural adherent pulmonary lesions.

PMID- 24327475
TI  - Rhenium and technetium tricarbonyl complexes of 1,4-Substituted pyridyl-1,2,3
      triazole bidentate 'click' ligands conjugated to a targeting RGD peptide.
AB  - New 1,4-substituted pyridyl-1,2,3-triazole ligands with pendent phenyl
      isothiocyanate functional groups linked to the heterocycle through a short
      methylene or longer polyethylene glycol spacers were prepared and conjugated to a
      peptide containing the arginine-glycine-aspartic acid peptide motif. Rhenium and
      technetium carbonyl complexes, [M(CO)3 L(x) (py)](+) (where M = Re(I) or (99m)
      Tc(I) ; L(x)  = 1,4-substituted pyridyl-1,2,3-triazole ligands and py = pyridine)
      were prepared. One rhenium complex has been characterized by X-ray
      crystallography, and the luminescent properties of [M(CO)3 L(x) (py)](+) are
      reported. 

PMID- 24327474
TI  - Filamin A interacting protein 1-like inhibits WNT signaling and MMP expression to
      suppress cancer cell invasion and metastasis.
AB  - Identifying key mediators of cancer invasion and metastasis is crucial to the
      development of new and more effective therapies. We previously identified FILamin
      A Interacting Protein 1-Like (FILIP1L) as an important inhibitor of cell
      migration and invasion. FILIP1L expression was inversely correlated with the
      invasive potential of ovarian tumors. In our study, we established an orthotopic
      ovarian cancer model, wherein FILIP1L expression can be regulated in vivo. Using
      this model, we observed that expression of FILIP1L in ovarian cancer cells
      inhibited spontaneous lung metastasis. Experimental lung metastases (established
      via tail vein injection of cancer cells) as well as the extravasation step of
      metastasis were not inhibited by FILIP1L, suggesting that FILIP1L inhibits the
      earlier steps of metastasis such as invasion and intravasation. FILIP1L inhibited
      matrix metalloproteinase (MMP)-dependent invasion in vivo. MMP3, -7 and -9 were
      transcriptionally downregulated, and MMP9 protein expression and activity were
      inhibited in FILIP1L-expressing tumors. Importantly, overexpression of MMP9
      compensated for the anti-invasive activity of FILIP1L. Furthermore, our studies
      suggest that FILIP1L regulates invasion and metastasis by inhibiting components
      of the WNT signaling pathway. FILIP1L expression reduced the induction of WNT
      target genes such as MMP3, -7 and -9, and beta-catenin-directed transcriptional
      activity, suggesting inhibition of the canonical WNT pathway. Nuclear beta
      catenin, an indicator of an active canonical WNT pathway, was reduced in FILIP1L
      expressing tumors. Overall, these findings suggest that FILIP1L reduces beta
      catenin levels, which may lead to the transcriptional downregulation of WNT
      target genes such as MMPs, resulting in inhibition of metastasis. Modulation of
      FILIP1L expression has the potential to be a target for cancer therapy. 

PMID- 24327476
TI  - Frequency and outcomes of aortocoronary dissection during percutaneous coronary
      intervention of chronic total occlusions: a case series and systematic review of
      the literature.
AB  - BACKGROUND: Aortocoronary dissection can complicate percutaneous coronary
      intervention (PCI) of chronic total occlusions (CTOs). METHODS: We
      retrospectively examined the frequency and outcomes of aortocoronary dissection
      among 336 consecutive CTO PCIs performed at our institution between 2005 and 2012
      and performed a systematic review of the published literature. RESULTS:
      Aortocoronary dissection occurred in six patients (1.8%, 95% confidence intervals
      0.7%, 3.8%). All aortocoronary dissections occurred in the right coronary artery
      (CTO target vessel in five patients and donor vessel in one patient). The
      baseline clinical characteristics of patients with and without aortocoronary
      dissection were similar. Compared to patients without, those with aortocoronary
      dissection were more likely to undergo crossing attempts using the retrograde
      approach (25% vs. 67%, P = 0.036) and experience a major complication (2.4% vs.
      33.3%, P = 0.008). Technical and procedural success rates were similar in both
      groups. Of the six patients with aortocoronary dissection one underwent emergency
      coronary bypass graft surgery (CABG), four were treated with ostial stenting, and
      one was treated conservatively without subsequent adverse clinical outcomes.
      Systematic literature review provided 107 published cases of aortocoronary
      dissection during PCI, that occurred mainly in the right coronary artery (74.8%)
      and were treated with stenting (49.5%), emergency CABG (29%), or conservatively
      (21.5%). CONCLUSIONS: Aortocoronary dissection is an infrequent complication of
      CTO PCI and although it can be treated with stents in most patients, it may
      infrequently require emergency CABG.

PMID- 24327477
TI  - Maternal obesity and risk of Down syndrome in the offspring.
AB  - OBJECTIVE: The objective of this article is to determine if maternal obesity is
      associated with an increased risk of Down syndrome in the offspring and whether
      the risk estimates for trisomy 21 based on combined screening is affected by
      maternal body mass index (BMI). METHODS: Study group I consisted of a nationwide
      cohort of 1 568 604 women giving birth; outcome was infants born with Down
      syndrome [Correction made here after initial online publication.]. Adjustment was
      made for maternal age. Study group II consisted of 10 224 women undergoing 1st
      trimester combined screening. Outcome was risk assessment for Down syndrome. All
      women were divided into six BMI groups, and outcomes were evaluated over the BMI
      strata with BMI 18.5 to 24.9 as reference and correcting for maternal age.
      RESULTS: Obese women had an increased risk for giving birth to an infant with
      Down syndrome compared with normal-weight women, BMI 30 to 34.9 odds ratio (OR)
      1.31 [95% confidence interval (CI) 1.10-1.55], BMI 35 to 39.9 OR 1.12 (95% CI
      0.82-1.53), BMI >= 40 OR 1.56 (95% CI 1.00-2.43). The observed and the expected
      numbers of women with a risk of Down syndrome >1/300 based on 1st trimester
      combined screen and maternal age were similar in each BMI group. CONCLUSION:
      Maternal obesity seems to increase the risk for Down syndrome births. The risk
      estimate for Down syndrome with 1st trimester combined screening is unaffected by
      BMI.

PMID- 24327478
TI  - Bio-inspired hierarchical polymer fiber-carbon nanotube adhesives.
AB  - Hierarchical pillar arrays consisting of micrometer-sized polymer setae covered
      by carbon nanotubes are engineered to deliver the role of spatulae, mimicking the
      fibrillar adhesive surfaces of geckos. These biomimetic structures conform well
      and achieve better attachment to rough surfaces, providing a new platform for a
      variety of applications. 

PMID- 24327479
TI  - A new source of mesenchymal stem cells for articular cartilage repair: MSCs
      derived from mobilized peripheral blood share similar biological characteristics
      in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model.
AB  - BACKGROUND: Bone marrow (BM) has been considered as a major source of mesenchymal
      stem cells (MSCs), but it has many disadvantages in clinical application.
      However, MSCs from peripheral blood (PB) could be obtained by a less invasive
      method and be more beneficial for autologous transplantation than BM MSCs, which
      makes PB a promising source for articular cartilage repair in clinical use.
      PURPOSE: To assess whether MSCs from mobilized PB of New Zealand White rabbits
      have similar biological characteristics in vitro and chondrogenesis in vivo as BM
      MSCs. STUDY DESIGN: Controlled laboratory study. METHODS: A combined method of
      drug administration containing granulocyte colony stimulating factor (G-CSF) plus
      CXCR4 antagonist AMD3100 was adopted to mobilize the PB stem cells of adult New
      Zealand White rabbits in vitro. The isolated cells were identified as MSCs by
      morphological characteristics, surface markers, and differentiation potentials. A
      comparison between PB MSCs and BM MSCs was made in terms of biological
      characteristics in vitro and chondrogenesis in vivo. This issue was investigated
      from the aspects of morphology, immune phenotype, multiple differentiation
      capacity, expansion potential, antiapoptotic capacity, and ability to repair
      cartilage defects in vivo of PB MSCs compared with BM MSCs. RESULTS: Peripheral
      blood MSCs were successfully mobilized by the method of combined drug
      administration, then isolated, expanded, and identified in vitro. No significant
      difference was found concerning the morphology, immune phenotype, and
      antiapoptotic capacity between PB MSCs and BM MSCs. Significantly, MSCs from both
      sources compounded with decalcified bone matrix showed the same ability to repair
      cartilage defects in vivo. For multipluripotency, BM MSCs exhibited a more
      osteogenic potential and higher proliferation capacity than PB MSCs, whereas PB
      MSCs possessed a stronger adipogenic and chondrogenic differentiation potential
      than BM MSCs in vitro. CONCLUSION: Although there are some differences in the
      proliferation and differentiation aspects between the 2 sources, PB MSCs share
      certain similar biological characteristics in vitro and chondrogenesis in vivo as
      BM MSCs. CLINICAL RELEVANCE: These results suggest that PB MSCs are a new source
      of seed cells used in articular cartilage repair.

PMID- 24327480
TI  - Informal care of patients with schizophrenia.
AB  - BACKGROUND: Schizophrenia is a disease that causes strong societal rejection and
      requires a significant allocation of healthcare and social resources. The
      chronicity and characteristics of the disease require continued care, often
      provided by nonprofessionals close to the person diagnosed with schizophrenia.
      AIM OF STUDY: To analyze the value of informal care associated with the loss of
      personal autonomy (dependency) caused by schizophrenia in Spain; to study the
      association between the level of dependency and the number of hours of informal
      care provided; and to examine the association between the level of
      dependency/hours of informal care and the burden borne by caregivers. METHODS: We
      used the Survey on Disabilities, Autonomy and Dependency to obtain information on
      the characteristics of disabled individuals with schizophrenia and the
      individuals who provide them with personal care. Assessment of informal care time
      was performed using the proxy good method. Statistical multivariate analyses
      using ordered probit models were conducted to study the impact of the degree of
      dependency on the hours of care provided and probit models to study the burden
      placed on caregivers in terms of health, professional, and leisure/social
      dimensions. RESULTS: The economic value of care varies between 523.06 and 866.7
      euro per week censoring at 16 hours of care per day (667.22-1,105.66 when no time
      censored). A primary informal caregiver of a severe or greatly dependent
      individual with schizophrenia was between 20.5% and 23.8% more likely to provide
      a high level of informal care (over 70 hours per week), between 6.1% and 6.4%
      less likely to provide a medium level of informal care (between 31 and 70 hours
      per week), and between 14.4% and 17.6% less likely to provide low-level care (30
      hours or less per week). Informal caregivers who provide care for
      severely/greatly dependent or moderately dependent people had a higher
      probability of suffering from health, professional, and family/socially related
      problems than caregivers who cared for non-dependent people. DISCUSSION AND
      CONCLUSIONS: The results show a part of the high social cost of schizophrenia in
      Spain. At the same time, the study provides evidence that more severe levels of
      dependency are positively associated with more hours of informal care and higher
      caregiver burden. IMPLICATIONS FOR HEALTH POLICY: The results show that health or
      social care programs targeted at persons with autonomy limitations cannot
      overlook the importance of informal care, since doing so would lead to
      inefficiencies or inequities and reduce the well-being of citizens. IMPLICATIONS
      FOR FURTHER RESEARCH: Information on informal care should be incorporated in the
      design of health and social care policies geared toward improving equity and
      efficiency in the allocation of social resources. Longitudinal studies of
      patients diagnosed with schizophrenia would provide further information on the
      characteristics and impact of informal care.

PMID- 24327481
TI  - Geographical inequalities in suicide rates and area deprivation in South Korea.
AB  - BACKGROUND: Recent years have witnessed growing interest in determinants of
      suicide in South Korea. While much of the research has paid attention to the role
      of individual factors in explaining suicide mortality, another potentially
      important dimension of health inequality is geography. AIMS OF THE STUDY: To
      describe the geographical distribution of suicide rates in South Korea, and to
      examine to what extent the distribution is shaped by area deprivation. METHODS:
      Using 2004-2006 mortality data and 2005 population census data, the study first
      described the spatial mapping of age-standardised suicide rates and level of area
      deprivation across 250 districts in South Korea. A spatial lag model was also
      employed to examine the association between the two, taking into account the
      spatial dependence and interactions between neighbouring districts, as indicated
      by Moran's I and Geary' C statistics. In addition to level of area deprivation,
      population density, welfare spending, and rates of divorce, marriage and
      fertility at district-level were added to the model. RESULTS: The spatial mapping
      of suicide rates across 250 districts exhibited a different pattern between males
      and females. While the highest suicide rates tended to cluster in the north-east
      region of South Korea for males, no clear pattern was observed for females. On
      the other hand, the lowest suicide rates for both males and females were found in
      most districts of the capital city. The results of the spatial lag model revealed
      a significant association between suicide rates and area deprivation,
      particularly for male suicide. Compared to the least deprived area, there were
      about 12-13 more male suicide cases (per 100,000 males) in highly deprived areas.
      The association with area deprivation was less clear for females. Population
      density was negatively associated with suicide rates for both males and females.
      While suicide rates were in general positively associated with divorce rates and
      negatively associated with fertility rates, the coefficients of both were not
      significant in the model for females. DISCUSSION AND LIMITATIONS: The study
      highlighted substantial geographical variation in suicide rates across South
      Korea. Such variation can be largely explained by level of area deprivation,
      especially for males. The level of excess suicides (i.e. 12-13 per 100,000 males)
      in highly deprived areas was similar to the average suicide rates of OECD
      countries. Due to the paucity of individual-level data however, the study was
      unable to test whether or not these associations were independent of population
      composition. IMPLICATIONS FOR HEALTH POLICIES: Prioritising development in
      relatively more deprived areas would potentially minimise resource barriers.
      Since such area-based approaches focus on a body with clear responsibility (i.e.
      local authority) and a greater relevance for local residents, programmes and
      services can be more effectively tailored to local needs and also more
      effectively delivered to local residents. IMPLICATIONS FOR FURTHER RESEARCH:
      Alternative sources of data with individual-level data should be explored to
      strengthen the basis of the present findings, and also to examine the exact
      mechanism underlying the associations between suicide rates and area deprivation.

PMID- 24327482
TI  - Economic analysis of an internet-based depression prevention intervention.
AB  - BACKGROUND: The transition through adolescence places adolescents at increased
      risk of depression, yet care-seeking in this population is low, and treatment is
      often ineffective. In response, we developed an Internet-based depression
      prevention intervention (CATCH-IT) targeting at-risk adolescents. AIMS OF THE
      STUDY: We explore CATCH-IT program costs, especially safety costs, in the context
      of an Accountable Care Organization as well as the perceived value of the
      Internet program. METHODS: Total and per-patient costs of development were
      calculated using an assumed cohort of a 5,000-patient Accountable Care
      Organization. Total and per-patient costs of implementation were calculated from
      grant data and the Medicare Resource-Based Relative Value Scale (RBRVS) and were
      compared to the willingness-to-pay for CATCH-IT and to the cost of current
      treatment options. The cost effectiveness of the safety protocol was assessed
      using the number of safety calls placed and the percentage of patients receiving
      at least one safety call. The willingness-to-pay for CATCH-IT, a measure of its
      perceived value, was assessed using post-study questionnaires and was compared to
      the development cost for a break-even point. RESULTS: We found the total cost of
      developing the intervention to be USD 138,683.03. Of the total, 54% was devoted
      to content development with per patient cost of USD 27.74. The total cost of
      implementation was found to be USD 49,592.25, with per patient cost of USD
      597.50. Safety costs accounted for 35% of the total cost of implementation. For
      comparison, the cost of a 15-session group cognitive behavioral therapy (CBT)
      intervention aimed at at-risk adolescents was USD 1,632 per patient. Safety calls
      were successfully placed to 96.4% of the study participants. The cost per call
      was USD 40.51 with a cost per participant of USD 197.99. The willingness-to-pay
      for the Internet portion of CATCH-IT had a median of USD 40. The break-even point
      to offset the cost of development was 3,468 individuals. DISCUSSION AND
      LIMITATIONS: Developing Internet-based interventions like CATCH-IT appears
      economically viable in the context of an Accountable Care Organization.
      Furthermore, while the cost of implementing an effective safety protocol is
      proportionally high for this intervention, CATCH-IT is still significantly
      cheaper to implement than current treatment options. Limitations of this research
      included diminished participation in follow-up surveys assessing willingness-to
      pay. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE AND HEALTH POLICIES: This
      research emphasizes that preventive interventions have the potential to be
      cheaper to implement than treatment protocols, even before taking into account
      lost productivity due to illness. Research such as this business application
      analysis of the CATCH-IT program highlights the importance of supporting
      preventive medical interventions as the healthcare system already does for
      treatment interventions. IMPLICATIONS FOR FURTHER RESEARCH: This research is the
      first to analyze the economic costs of an Internet-based intervention. Further
      research into the costs and outcomes of such interventions is certainly warranted
      before they are widely adopted. Furthermore, more research regarding the safety
      of Internet-based programs will likely need to be conducted before they are
      broadly accepted.

PMID- 24327483
TI  - Perspectives: the mental health care gap in intellectual disabilities in Spain:
      impact analysis and knowledge-to-action plan.
AB  - BACKGROUND: Intellectual developmental disorder or Intellectual disability (ID)
      is a prevalent condition with a high impact along the life-span particularly when
      associated to other mental disorders (MD). SPECIFIC AIM: To estimate the unmet
      needs and to design a knowledge to action plan to reduce the care gap in ID-MD in
      Spain. METHOD: We followed a 5-step 'maxi' impact assessment and a mixed
      qualitative/quantitative design including expert panels, secondary analysis of
      databases and a prospective survey in the 17 regions in Spain. Schizophrenia was
      used as comparator due to similar prevalence rates and burden. RESULTS: Persons
      with ID-MD had ten times less outpatient contacts and hospital admissions than
      patients with schizophrenia. The outpatient case load was 2.31% in ID and 14.6%
      in schizophrenia. ID had the lowest hospitalization rate amongst all mental
      disorders but the highest length of stay. The expert panel estimated that half of
      persons with ID-MD are not adequately assessed and 95% do not receive the
      required care in Spain. Basic care needs include 6.5 beds and an ID-MD outpatient
      service per 1 million population. At least 134 specialized psychiatrists and
      psychologists and 277 beds are needed to reach the minimum standards in Spain.
      CONCLUSION: This study quantifies the ID-MD care gap in Spain and the basic
      specialized services needed. In spite of the societal and health implications of
      ID-MD the knowledge-to-action plan had a modest impact limited at the regions
      where ID-MD programmes were already implemented. IMPLICATIONS FOR HEALTH POLICY:
      Specific priority setting on ID-MH should be incorporated to mental health
      strategy at the Ministry of Health within a broader health and ID plan. National
      and regional policies should incorporate an integrative care approach through the
      life cycle. The development of excellence centers on ID-MD and a national
      observatory on this topic should be encouraged.

PMID- 24327484
TI  - [Prognostic Value of Preoperative Anaemia and Perioperative Blood Transfusion in
      Surgical Treatment of Rectal Cancer].
AB  - INTRODUCTION: There is evidence for the prognostic value of perioperative blood
      transfusion in the surgical treatment of patients with rectal cancer in the
      current literature. Also preoperative anaemia seems to have an impact on the
      outcome of these patients. The aim of this study was to evaluate the impact of
      preoperative anaemia and perioperative blood transfusion in patients with rectal
      cancer treated in our hospital. PATIENTS AND METHODS: 208 patients (81 females,
      127 males; median age, 67 years) with rectal cancer were included in this
      retrospective study. All patients received surgical treatment. In 75 % of the
      patients an anterior rectum resection was performed while 25 % received an
      abdominoperineal rectum exstirpation. Patients with neoadjuvant treatment were
      included and statistical analyses were performed. RESULTS: 107 (51.4 %) patients
      exhibited preoperative anaemia. Patients with neoadjuvant treatment presented
      with significantly lower preoperative Hb (haemoglobin) values than patients
      without neoadjuvant treatment (p = 0.022). Patients with preoperative anaemia
      received significantly more blood transfusions (p = 0.001), had significantly
      longer hospital stays (p = 0.023) and significantly lower 5-years overall
      survival (p = 0.005). Blood transfusion was necessary in 82 patients (39.4 %).
      These patients presented with a significantly higher rate of perioperative
      complications (p = 0.01) and a lower 5-years overall survival (p = 0.002). In
      multivariate analyses neither preoperative anaemia nor perioperative transfusion
      was a significant prognostic factor. CONCLUSION: In our study preoperative
      anaemia and perioperative blood transfusion seems to have an impact on outcome of
      surgical treatment of patients with rectal cancer. However, in multivariate
      analyses neither preoperative anaemia nor perioperative transfusion was a
      significant prognostic factor.

PMID- 24327485
TI  - [Preoperative Information: What Do Patients Want to Know?].
AB  - BACKGROUND: Aimed at supporting patient information, media forms were developed.
      While doing so patient views were predominantly not considered. Moreover, for one
      of the most common surgical procedures, herniated disk surgery, there rarely
      exists appropriate information material. PATIENTS AND METHODS: 29 people with
      experience of back pain were recruited to participate in focus group interviews,
      where conditions of satisfying consultations and needs regarding the design of an
      education film for herniated disk surgery were analysed. RESULTS: Frame
      conditions, desired education media and factors relating to the physician compose
      three complexes of general satisfaction criteria. Needs in terms of form and
      content design of an education film were discussed and registered in detail.
      CONCLUSION: Existing guidelines considering patient education are extensively
      consistent with patients' desires and should be implemented obligatorily. The use
      of audio-visual media as well as medical students' and physicians' training in
      soft skills requires expansion.

PMID- 24327486
TI  - [Hereditary syndromes of neuroendocrine tumours].
AB  - Diffuse localised neuroendocrinal cells represent the largest population of
      endocrinally active cells and can degenerate to malignant neuroendocrine tumours
      (NET). In this review the most important hereditary syndromes that predispose for
      endocrine and neuroendocrine tumours are presented and discussed. NET occur
      mainly as sporadic tumours. Current investigations on the pathogenesis of
      sporadic neuroendocrine tumours have revealed a close relationship between
      hereditary and sporadic neuroendocrine tumours. In the course of hereditary
      syndromes, such as multiple endocrine neoplasia, endocrine and neuroendocrine
      tumours as well as non-endocrine neoplasias can occur. In order to recognise
      these syndromes in good time a knowledge of the predisposing syndromes and their
      cardinal symptoms is essential. In this way not only individualised diagnosis and
      therapy can be planned but also an appropriate early management of first degree
      relatives can be initiated. 

PMID- 24327487
TI  - [What should a surgeon know about family medicine?].
AB  - BACKGROUND: Surgeons have only limited options from case-specific contacts to
      generate a comprehensive picture about family medicine as a discipline and the
      family practitioner with its specific issues and characteristics. Thus, the
      typical function of the family practitioner is often not sufficiently taken into
      account while aiming for a better cooperation: the primary care of "unselected
      reasons for encounter" with integration of bio-psycho-social aspects, long-term
      care, close distance contacts and low-threshold access. In addition, family
      practitioners and surgeons have different expectations regarding their
      cooperation, which are important to know and handle. METHODS: A selective
      literature search was undertaken on the self-conception and professional
      functioning of family medicine as well as on mutual expectations to improve
      cooperation at the outpatient-inpatient interface. RESULTS/CONCLUSION: Surgeons
      benefit from the knowledge on self-conception and functioning of family
      practitioners by using options and potentials for the reduction of problems at
      the outpatient-inpatient interface and for an optimised network.

PMID- 24327488
TI  - [The significance of contrast-enhanced ultrasound in vascular surgery].
AB  - BACKGROUND: Vascular contrast-enhanced ultrasound (CEUS) is a special ultrasound
      application without the harmful side effects of nephrotoxicity and radiation
      exposure. CEUS can be used for advanced diagnosis of carotid stenosis and follow
      up checks of endovascular repair of abdominal aortic aneurysms (EVAR). Low-flow
      phenomenon in peripheral vascular disease can easily be detected by enhanced
      colour-coded duplex sonography (CCDS). METHODS: The technical requirements of
      CEUS are explained here for the aorta, carotid, and peripheral arteries. The
      benefits and risks compared to computed tomography (CT), magnetic resonance (MR)
      and angiography are evaluated. Based on a selective review of the literature and
      the authors' personal experiences, CEUS is recommended for routine surveillance
      after EVAR. RESULTS: CEUS is a safe method using SonoVue(r) (Bracco) as the only
      approved agent for vascular examination. Special equipment and training is
      necessary. In prospective studies and meta-analyses the detection and
      characterisation of endoleaks is comparable to that of CT imaging.
      Neovascularisation as a sign of carotid plaques at risk can be seen without the
      need for invasive treatment. Imaging of crural vessels with enhanced CCDS is a
      promising but rarely needed option in diabetic and renally insufficient patients.
      CONCLUSION: CEUS in vascular medicine should be performed prior to other methods
      to avoid nephrotoxic contrast agents for the patients, especially in follow-up
      checks after EVAR. The time and effort required are still limiting its practical
      breakthrough.

PMID- 24327489
TI  - [Immunomodulatory aspects in the development, prophylaxis and therapy for
      postoperative ileus].
AB  - Postoperative ileus (POI) is defined as a transient episode of impaired
      gastrointestinal motility after abdominal surgery, which prevents effective
      transit of intestinal contents or tolerance of oral intake. This frequent
      postoperative complication is accompanied by a considerable increase in morbidity
      and hospitalisation costs. The aetiology of POI is multifactorial. Besides a
      suppression of peristalsis by inhibitory neuronal signalling and administration
      of opioids, particularly in the prolonged form, immunological processes play an
      important role. After surgical trauma, resident macrophages of the muscularis
      externa (ME) are activated leading to the liberation of proinflammatory mediators
      and a spreading of the inflammation along the entire gastrointestinal tract. To
      date, no prophylaxis or evidence-based single approach exists to treat POI. Since
      none of the current treatment approaches (i.e., prokinetic drug treatment) has
      provided a benefit in randomised trials, immunoregulatory interventions appear to
      be more promising in POI prevention or treatment. The present contribution gives
      an overview of immunological mechanisms leading to POI focusing on current and
      future therapeutic and prophylactic approaches. 

PMID- 24327490
TI  - Off-label drug use in the pediatric cardiac intensive care unit.

PMID- 24327491
TI  - Patient age at the Ross operation in children influences aortic root dimensions
      and aortic regurgitation.
AB  - BACKGROUND: The Ross operation provides the advantage of growth potential of the
      pulmonary autograft in the aortic position. However, development of autograft
      dilatation and regurgitation may occur. We sought to assess the progression of
      autograft diameters and aortic regurgitation (AR) with regard to patient age at
      the time of the Ross operation. METHODS: Autograft echo dimensions from 48
      children <16 years of age at the time of the Ross operation, who had follow-up
      echocardiograms at <20 years of age, were analyzed using hierarchical multilevel
      modeling. The z values of autograft dimensions were calculated according to the
      normal aortic dimensions. Mean follow-up was 5.1 +/- 3.3 years. The mean age at
      the time of the Ross operation was 10.0 +/- 4.3 years. RESULTS: The mean z values
      of all patients showed a significant increase with follow-up time at the sinus
      (0.5 +/- 0.1/year, P < .001) and the sinotubular junction (0.7 +/- 0.2/year, P <
      .001) but not at the annulus (0.1 +/- 0.1/year, P = .59). There was no
      significant difference in the z values of sinus and the sinotubular junction
      between younger and older children at implantation and with time. The initial
      annulus z value was significantly larger in younger children (P < .0001), whereas
      the annual increase was significantly higher in older children (P = .021). Age at
      operation has no impact on the initial AR grade (P = .60). The AR tends to
      increase more quickly in older patients (P = .040). Sinus and sinotubular
      junction dilate with time, regardless of patient age. CONCLUSIONS: Young children
      show larger initial annulus sizes than older children. However, annulus diameters
      tend to normalize in young children, whereas they increase in older children.
      Autograft regurgitation develops slowly, but significantly, and predominantly in
      older children. Stabilizing measures to prevent autograft root dilatation are
      warranted in adolescents, but they are not required in young children.

PMID- 24327492
TI  - Subaortic membrane and aorto-septal angle: an echocardiographic assessment and
      surgical outcome.
AB  - BACKGROUND: Development of a subaortic membrane is not fully understood.
      Recurrence after surgical removal continues to be high. We sought to assess the
      differences in aorto-septal angles (AoSA) to possibly explain alterations within
      the left ventricular outflow tract, hence in subaortic membrane formation.
      METHODS: A total of 113 patients who underwent subaortic membrane resection were
      matched by age and sex with 113 controls. The subaortic membrane resection group
      included isolated subaortic membranes (n = 34, group I), associated with
      ventricular septal defect (n = 29, group II), or patent ductus arteriosus (n =
      50, group III). RESULTS: Mean (+/- standard deviation) AoSA (in degrees) were not
      different between subaortic membrane groups I, II, and III but were steeper than
      their control groups (126.2 +/- 9.2 vs 138.6 +/- 7.0, 129.2 +/- 9.9 vs 137.7 +/-
      10.0, and 126.2 +/- 8.1 vs 135 +/- 8.5, respectively; all Ps < .05).
      Additionally, group II had lower preoperative gradients (28.8 +/- 20.7 mm Hg)
      compared to groups I and III (67.0 +/- 32.9 and 66.2 +/- 33.1 mm Hg,
      respectively, P < .001). Follow-up ranged from 3 to 132 months. In 22 (32%)
      patients, a subaortic membrane recurred. Early postoperative residual gradients
      and development of aortic regurgutation were associated with the need for
      reoperation (P < .05). CONCLUSIONS: These findings suggest a contributing role of
      the AoSA in the development of subaortic membrane. Further rheological
      experiments are warranted. Whether the steeper the angle the higher the risk of
      recurrence may be revealed by longer follow-up periods.

PMID- 24327493
TI  - Off-label drug use in a single-center pediatric cardiac intensive care unit.
AB  - BACKGROUND: The frequency of off-label drug use and its association with
      morbidity and mortality in the cardiac intensive care unit (CICU) has not been
      previously studied. METHODS: Patients less than 18 years of age admitted to the
      CICU from June to August 2008 were retrospectively identified. Patient
      demographics were collected for 30 days or until CICU discharge. Off-label drug
      use was defined as the prescription of a medication that lacked a labeled
      indication based on patient's age as reported in the Micromedex drug database and
      electronic Physician's Desk Reference. RESULTS: Eighty-two patients were admitted
      to the CICU during the study period. In all, 40 (46%) patients were male; the
      median age was 10.6 months. Common diagnoses were left-to-right shunt lesions
      (20.7%) and single-ventricle lesions (20.7%), with an overall mortality of 2.4%.
      Of all drugs prescribed, 36% were off-label. In all, 94% of the patients received
      >=1 drug off-label. The median number of drugs prescribed off-label was four.
      Patients receiving more than four off-label medications were younger, had longer
      CICU lengths of stay (median 9.5 vs 2 days, P < .001), and increased ventilator
      days (median two vs one day, P < .001). CONCLUSIONS: Off-label drug use in the
      CICU is common. Frequency of use is likely higher in patients with a higher
      severity of illness. Further safety, efficacy, and pharmaceutical trials are
      warranted to optimize the use of these drugs to improve outcomes.

PMID- 24327494
TI  - Staphylococcus aureus colonization in children undergoing heart surgery.
AB  - BACKGROUND: Staphylococcus aureus is an important cause of cardiac surgical site
      infection. Based on studies in adults, nasal screening to detect S
      aureuscolonization is used to guide decolonization and selection of prophylactic
      antibiotics. In our Children's Hospital, a sensitive polymerase chain reaction
      (PCR)-based assay is used to screen patients undergoing cardiac surgery for nasal
      colonization with methicillin-sensitive S aureus (MSSA) and methicillin-resistant
      S aureus (MRSA). Additionally for patients in diapers, cultures are used to
      detect MRSA colonization of the groin. The purpose of this study was to determine
      whether screening two anatomic locations results in a higher MRSA detection rate
      among children undergoing cardiac surgery. METHODS: A retrospective chart review
      determined whether the frequency of bacterial colonization with MRSA differed by
      anatomic site. Records for 322 pediatric cardiac surgery procedures performed
      between January 2009 and June 2011 were reviewed. Both a nasal PCR and a second
      anatomic site culture were performed before 102 procedures. RESULTS: The overall
      rate of colonization with MRSA and MSSA was 4.2% and 29.1%, respectively. Of the
      seven dually screened patients who tested positive for MRSA, two were identified
      solely via a groin test, four by nasal screening alone, and one by both the
      tests. Screening of only the nose would have failed to detect 28.6% of the MRSA
      cases. CONCLUSION: Preoperative detection of MRSA colonization may be enhanced by
      screening both the nose and a second anatomic site. The clinical utility of the
      extranasal MRSA culture was limited due to the long assay turnaround time.

PMID- 24327495
TI  - Morphology, surgical techniques, and outcomes in patients above 15 years
      undergoing surgery for congenitally corrected transposition of great arteries.
AB  - BACKGROUND: There is a paucity of data about morphology, surgical procedure, and
      results in older patients with congenitally corrected transposition of great
      arteries (ccTGAs). PATIENTS AND METHODS: Between January 2002 and August 2012, 15
      patients (7 males), median age 25 years, range 16 to 41 years underwent surgery
      for ccTGA. Associated lesions were tricuspid regurgitation (TR; n = 5) and
      ventricular septal defect (VSD) with pulmonary stenosis (PS; n = 10). Surgical
      procedures included tricuspid valve replacement (n = 4), tricuspid valve repair
      (n = 1), lateral tunnel Fontan (n = 2), extracardiac Fontan (n = 2), Kawashima
      procedure (n = 1), bidirectional (BD) Glenn (n = 2), Senning + Rastelli procedure
      (n = 1), and VSD closure + left ventricle to pulmonary artery conduit (n = 1).
      The details of these procedures and outcomes were analyzed. RESULTS: There were
      no early or late deaths. Mean follow-up period was 49.9 +/- 26 months. All
      patients who underwent tricuspid valve replacement are in New York Heart
      Association (NYHA) class I, with no progression of right ventricular (RV)
      dysfunction. One patient who underwent tricuspid valve repair is in NYHA class
      III and has progressed to severe RV dysfunction. None of the patients undergoing
      single ventricle palliation had any complications related to the surgery. Both
      patients who underwent anatomical and physiological biventricular (BV) repair had
      no complications. CONCLUSIONS: Older patients with ccTGA present a challenge.
      Fontan/BD Glenn remains a good option for patients who presented with VSD PS.
      Both anatomic and physiological BV repairs provide acceptable results. Tricuspid
      valve replacement is safe for patients presenting with TR who have improvement in
      functional class, though the right ventricular function may not improve.

PMID- 24327496
TI  - Infant cardiac surgery: mothers tell their story: a therapeutic experience.
AB  - BACKGROUND: Serious congenital heart disease frequently requires major congenital
      heart surgery. It causes much distress for parents, which may not always be
      recognized and treated appropriately. PATIENTS AND METHODS: As part of a larger
      study, 26 mothers of two-month-old infants subjected to recent cardiac surgery
      were interviewed in depth. Each mother was invited to describe her own and what
      she perceived were her infant's experiences and to comment on the interview
      process. A systematic content analysis of the interviews was performed using
      qualitative research methodology. RESULTS: Almost all participants described
      acute stress symptoms relating to the diagnosis and the infant's surgery. In
      addition, most mothers reported that the interview helped them to think about and
      integrate what had happened to them and their infant, suggesting a probable
      therapeutic value to the interview. CONCLUSIONS: A suitably qualified and
      experienced mental health professional, assisting the mother to tell her story
      about the diagnosis and her infant's cardiac surgery, may provide a valuable,
      brief, and very cost-effective therapeutic intervention for these mothers and
      infants. It has the potential to alleviate maternal distress, with associated
      gains for the developing mother-infant relationship, reducing infant morbidity,
      and enhancing the quality of life for both infant and mother.

PMID- 24327497
TI  - Potts shunt in a child with end-stage pulmonary hypertension after late repair of
      ventricular septal defect.
AB  - We report on a 10-year-old boy with medically refractory pulmonary arterial
      hypertension (PAH) and end-stage right heart failure after closure of a
      ventricular septal defect. The boy was a candidate for lung transplantation
      (LTX), but an alternative option was to create an Eisenmenger physiology with
      right-to-left shunting. The shunt could be created either as an intracardiac or
      as an extracardiac shunt. We decided to create a Potts shunt, a direct
      anastomosis between the left pulmonary artery and the descending aorta. The Potts
      shunt functioned as a right-to-left shunt, thus reducing the afterload on the
      right ventricle. The boy's clinical condition improved markedly, so he was
      discharged two weeks after the procedure. The ultimate therapeutic option for
      medically refractory PAH is LTX or heart-lung transplantation, but because of the
      short life span after LTX, time was bought by postponing the time of
      transplantation. 

PMID- 24327498
TI  - Left mammary artery bypass grafting rescued a patient with hypoplastic left heart
      syndrome with ascending aorta obstruction after norwood stage I procedure.
AB  - A three-month-old boy with hypoplastic left heart syndrome (mitral atresia,
      aortic atresia) and moderate tricuspid regurgitation developed ascending aorta
      obstruction two months after a Norwood stage I procedure. An emergent left
      mammary artery bypass grafting to the ascending aorta and extracorporeal membrane
      oxygenator support resulted in successful salvage. The patient subsequently
      underwent a bidirectional Glenn procedure and tricuspid valve repair at the age
      of five months. Follow-up at an outpatient clinic reveals no electrocardiographic
      evidence of ischemia, and echocardiography shows recovery of ventricular
      function. 

PMID- 24327499
TI  - Esophageal perforation associated with fontan operation: a complication of
      transesophageal echocardiography.
AB  - A 10-year-old girl with unbalanced atrioventricular septal defect and aortic arch
      interruption with interrupted inferior vena cava and dextrocardia had undergone a
      modified Norwood procedure followed by a Kawashima operation in 2002 and 2005,
      respectively. In 2012, she underwent Fontan operation with diversion of hepatic
      veins to left pulmonary artery. Intraoperative transesophageal echocardiography
      (TEE) was used. She was noted to have an esophageal perforation, diagnosed on the
      10th postoperative day. She was managed with thoracic drainage, cervical
      esophagostomy, and feeding jejunostomy. Esophageal perforation is a rare
      complication of TEE and requires very aggressive treatment. 

PMID- 24327500
TI  - Off-pump LIMA-RIMA Y graft: a practical option in adult-type ALCAPA.
AB  - A 29-year-old female was diagnosed to have adult-type anomalous left coronary
      artery from pulmonary artery (ALCAPA). She underwent a two-coronary system repair
      using left internal mammary artery and right internal mammary artery Y (LIMA-RIMA
      Y) off-pump coronary artery bypass grafting and made an uneventful postoperative
      recovery. The usage of off-pump LIMA-RIMA Y graft can be a suitable option for
      adult ALCAPA with a potential for good long-term outcomes. 

PMID- 24327501
TI  - Laubry-Pezzi syndrome with aortic root dilatation treated with a bentall and De
      Bono procedure.
AB  - Laubry-Pezzi syndrome is a clinical entity in which prolapse of an aortic valve
      cusp into a subjacent ventricular septal defect (VSD) due to Venturi effect
      results in progressive aortic valve insufficiency. Aortic valve prolapse is found
      in over 5% of children with VSDs, most commonly in association with supracristal
      VSDs, and the risk of development of aortic regurgitation increases during
      childhood, peaking at 5 to 10 years of age. The VSD closure eliminates the low
      pressure zone that is the cause of ongoing aortic valve cusp deformity and, if
      performed early, prevents the development of aortic regurgitation. However, the
      management of this rare pathology is still a matter of some debate with respect
      to indications, operative techniques, and timing. We report the case of a patient
      with Laubry-Pezzi syndrome, originally operated on at six years of age for VSD
      closure and plasty between the left and the right aortic cusps. However, in the
      follow-up the patient developed severe aortic regurgitation and aortic root
      dilatation. Eventually, a Bentall and De Bono procedure was performed. 

PMID- 24327502
TI  - Lusoria flap for the management of aortic coarctation in an eight-year-old child.
AB  - Anomalous origin of right subclavian artery arising from the descending aorta is
      known as "arteria lusoria." The diagnosis in asymptomatic children is usually the
      by-product of other symptomatic-associated anomalies, such as aortic coarctation.
      We describe a case of an eight-year-old boy with juxtaductal aortic coarctation
      and rare origin of the arteria lusoria proximal to the aortic coarctation. The
      anomalous arteria lusoria was used as a flap to repair the aortic coarctation. To
      the authors' knowledge, this is the first reported application of lusoria flap in
      a young child (not newborn) with ductal aortic coarctation. 

PMID- 24327503
TI  - Cardiac injury in child managed successfully in underprivileged hospital of
      Africa.
AB  - Cardiac injuries are rare and the associated mortality is high. Their prognosis
      can be ameliorated by early diagnosis and management in a specialized hospital
      with appropriate resuscitation care. This report describes a case of cardiac
      penetrating injury in a child managed successfully in an underprivileged hospital
      of Africa. 

PMID- 24327504
TI  - Topsy-turvy heart: a very rare congenital rotational heart disease with
      tracheobronchial anomalies.
AB  - The topsy-turvy heart is characterized by a global 90 degrees clockwise rotation
      around the heart's long axis. This rotation displaces all basal great arteries
      inferiorly and posteriorly, resulting in elongation and stretching of the
      brachiocephalic arteries and the bronchi. To date, reports of only four living
      cases have been published in the literature. We report here three new cases, with
      additional aortopulmonary window defects, and present their morphological
      details, clinical presentations, and our management. 

PMID- 24327505
TI  - Contained rupture of the sinus of valsalva associated with infective endocarditis
      and untreated congenital ventricular septal defect.
AB  - Isolated sinus of Valsalva (SV) aneurysm is a rare condition that may arise in
      patients with congenital ventricular septal defects (VSD). Small VSDs are often
      left untreated because of high rate of spontaneous closure. However,
      complications such as aortic regurgitation and infective endocarditis may occur
      as complications of small VSDs. We present the case of a 19-year-old man with a
      history of VSD, who presented with Staphylococcus aureus endocarditis and a
      contained rupture of the SV into the right ventricle, which was successfully
      treated. In the light of this case, we believe that even small VSDs should be
      assessed regularly and treated before such drastic complications occur. 

PMID- 24327506
TI  - Large pericardial cyst in an asymptomatic child: a case report.
AB  - We present a case report of a nine-year-old asymptomatic girl with a large cystic
      lesion of the left hemithorax, occupying almost 80% of the left hemithorax, first
      believed to be a parasitic cyst that was operated and proved to be of parietal
      pericardial origin. Mediastinal cysts and pericardial cysts in particular are
      mostly discovered accidentally and so was the case with our patient. The
      diagnosis included not only clinical examination but also the utilization of
      computed tomography and magnetic resonance imaging. The only treatment for
      pericardial cysts is surgical excision and patients recover fully with no
      complication. 

PMID- 24327507
TI  - Left ventricular diverticulum: how we do it.
AB  - Left ventricular diverticulum is an extremely rare anomaly, especially in the
      absence of other findings, and as such it has been rarely imaged, rarely seen
      intraoperatively, and has no standardized management algorithm. We report our
      suggested imaging and management in the context of previous management
      philosophies. 

PMID- 24327508
TI  - Tetralogy of fallot with absent pulmonary valve: imaging with today's diagnostic
      tools.

PMID- 24327509
TI  - Three-dimensional rotational angiography during percutaneous device closure of
      fontan fenestration.
AB  - The Fontan circulation was originally described as palliation for tricuspid
      atresia but was subsequently used for a wide variety of single-ventricle
      physiologies, with the common thread being inability to separate the ventricles
      for independent use in the systemic and pulmonary circulations. Fontan baffle
      fenestrations have been created since the late 1980s to assist in maintaining the
      cardiac output in the presence of increased resistance to flow through the
      pulmonary circuit. Many institutions continue to use an approach to Fontan
      circulation that utilizes routine fenestration followed by percutaneous device
      closure at a later time, whereas other institutions use fenestrations sparingly.
      We present the case of a five-year-old female with hypoplastic left heart
      syndrome with a fenestrated Fontan, who underwent three-dimensional rotational
      angiography at the time of catheterization for percutaneous device closure of the
      fenestration. 

PMID- 24327510
TI  - Diaphragmatic nerve palsy after cardiac surgery in children.

PMID- 24327511
TI  - Response to the letter "diaphragmatic nerve palsy after cardiac surgery in
      children: outcome and debate in management".

PMID- 24327512
TI  - Transition from residency to "independent" congenital heart surgeon: a lifelong
      process, not a graduation day.

PMID- 24327514
TI  - Clinical features and outcomes of young patients with head and neck non
      rhabdomyosarcoma soft tissue sarcomas.
AB  - BACKGROUND: The history, prognostic factors, and outcome of young patients with
      head and neck non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) have not been
      adequately characterized. METHODS: Medical records of 58 patients with head and
      neck NRSTS treated at St. Jude Children's Research Hospital were reviewed.
      RESULTS: The majority of tumors were <=5 cm and high grade. Lymph node and/or
      distant metastases were present in 17% at presentation. Patients received a
      combination of surgery, chemotherapy, and radiotherapy. The 10-year event-free
      and survival rates were 53.1% +/- 7.3% and 63.2% +/- 7.1%, respectively. Features
      associated with inferior survival included high histologic grade (p = .006),
      tumor diameter >5 cm (p < .001), invasiveness (p < .001), and incomplete
      resection at diagnosis (p = .005). CONCLUSION: Most head and neck NRSTS in young
      patients are small, high grade, and nonmetastatic. The outcome is poor compared
      to NRSTS at other anatomic sites. Innovative approaches to local control and
      improved systemic therapy are needed.

PMID- 24327515
TI  - Distribution of vesicular glutamate transporter 2 in auditory and song control
      brain regions in the adult zebra finch (Taeniopygia guttata).
AB  - The songbird brain has a system of interconnected nuclei that are specialized for
      singing and song learning. Wada et al. (2004; J. Comp. Neurol. 476:44-64) found a
      unique distribution of the mRNAs for glutamate receptor subunits in the song
      control brain areas of songbirds. In conjunction with data from
      electrophysiological studies, these finding indicate a role for the glutamatergic
      neurons and circuits in the song system. This study examines vesicular glutamate
      transporter 2 (VGLUT2) mRNA and protein expression in the zebra finch brain,
      particularly in auditory areas and song nuclei. In situ hybridization assays for
      VGLUT2 mRNA revealed high levels of expression in the ascending auditory nuclei
      (magnocellular, angular, and laminar nuclei; dorsal part of the lateral
      mesencephalic nucleus; ovoidal nucleus), high or moderate levels of expression in
      the telencephalic auditory areas (cudomedial mesopallium, field L, caudomedial
      nidopallium), and expression in the song nuclei (HVC, lateral magnocellular
      nucleus of the anterior nidopallium, robust nucleus of the arcopallium), where
      levels of expression were greater than in the surrounding brain subdivisions.
      Area X did not show expression of VGLUT2 mRNA. Nuclei in the descending motor
      pathway (dorsomedial nucleus of the intercollicular complex, retroambigual
      nucleus, tracheosyringeal motor nucleus of the hypoglossal nerve) expressed
      VGLUT2 mRNA. The target nuclei of VGLUT2 mRNA-expressing nuclei showed
      immunoreactivity for VGLUT2 as well as hybridization signals for the mRNA of
      glutamate receptor subunits. The present findings demonstrate the origins and
      targets of glutamatergic neurons and indicate a central role for glutamatergic
      circuits in the auditory and song systems in songbirds.

PMID- 24327516
TI  - Reply: To PMID 23907995.

PMID- 24327517
TI  - Rebuttal: "Closure of patent foramen ovale and prevention of recurrent
      thromboembolic events".

PMID- 24327518
TI  - Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in
      renal cancer.
AB  - Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine
      kinase, is a key regulator of numerous cellular processes ranging from glycogen
      metabolism to cell-cycle regulation and proliferation. Consistent with its
      involvement in many pathways, it has also been implicated in the pathogenesis of
      various human diseases, including type II diabetes, Alzheimer disease, bipolar
      disorder, inflammation, and cancer. Consequently, it is recognized as an
      attractive target for the development of new drugs. In the present study, we
      investigated the effect of both pharmacologic and genetic inhibition of GSK-3 in
      two different renal cancer cell lines. We have shown potent antiproliferative
      activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The antiproliferative
      activity is most likely caused by G(0)-G(1) and G(2)-M phase arrest as evident
      from cell-cycle analysis. We have established that inhibition of GSK-3 imparted a
      differentiated phenotype in renal cancer cells. We have also shown that GSK-3
      inhibition induced autophagy, likely as a result of imbalanced energy homeostasis
      caused by impaired glucose metabolism. In addition, we have demonstrated the
      antitumor activity of 9-ING-41 in two different subcutaneous xenograft renal cell
      carcinoma tumor models. To our knowledge, this is the first report describing
      autophagy induction due to GSK-3 inhibition in renal cancer cells.

PMID- 24327520
TI  - Leucine improves protein nutritional status and regulates hepatic lipid
      metabolism in calorie-restricted rats.
AB  - Several studies have highlighted the potential of leucine supplementation for the
      treatment of metabolic diseases including type 2 diabetes and obesity. Caloric
      restriction is a common approach to improve the health in diabetic and obese
      subjects. However, very few studies assessed the effects of leucine
      supplementation in calorie-restricted animals. Rats were subjected to a 30%
      calorie-restricted diet for 6 weeks to study the effects of leucine
      supplementation on protein status markers and lipid metabolism. Caloric
      restriction reduced the body weight. However, increased leucine intake preserved
      body lean mass and protein mass and improved protein anabolism as indicated by
      the increased circulating levels of albumin and insulin-like growth factor-1 (IGF
      1), and the liver expression of albumin and IGF-1 messenger RNA. Leucine
      supplementation also increased the circulating levels of interleukin-6 and leptin
      but did not affect the tumour necrosis factor-alpha and monocyte chemotactic
      protein-1 concentrations. Ketone bodies were increased in rats consuming a
      leucine-rich diet, but we observed no changes in cholesterol or triglycerides
      concentrations. Caloric restriction reduced the liver expression of peroxisome
      proliferator activated receptor-alpha and glucose-6-phosphatase, whereas leucine
      supplementation increased the liver expression of 3-hydroxy-3-methyl-glutaryl-CoA
      reductase (HMG-CoA) reductase and sterol regulatory element-binding transcription
      factor 1. A leucine-rich diet during caloric restriction preserved whole body
      protein mass and improved markers of protein anabolism. In addition, leucine
      modulated the hepatic lipid metabolism. These results indicate that increased
      leucine intake may be useful in preventing excessive protein waste in conditions
      of large weight loss.

PMID- 24327519
TI  - Combined MET inhibition and topoisomerase I inhibition block cell growth of small
      cell lung cancer.
AB  - Small cell lung cancer (SCLC) is a devastating disease, and current therapies
      have not greatly improved the 5-year survival rates. Topoisomerase (Top)
      inhibition is a treatment modality for SCLC; however, the response is short
      lived. Consequently, our research has focused on improving SCLC therapeutics
      through the identification of novel targets. Previously, we identified MNNG HOS
      transforming gene (MET) to be overexpressed and functional in SCLC. Herein, we
      investigated the therapeutic potential of combinatorial targeting of MET using
      SU11274 and Top1 using 7-ethyl-10-hydroxycamptothecin (SN-38). MET and TOP1 gene
      copy numbers and protein expression were determined in 29 patients with limited
      (n = 11) and extensive (n = 18) disease. MET gene copy number was significantly
      increased (>6 copies) in extensive disease compared with limited disease (P =
      0.015). Similar TOP1 gene copy numbers were detected in limited and extensive
      disease. Immunohistochemical staining revealed a significantly higher Top1
      nuclear expression in extensive (0.93) versus limited (0.15) disease (P = 0.04).
      Interestingly, a significant positive correlation was detected between MET gene
      copy number and Top1 nuclear expression (r = 0.5). In vitro stimulation of H82
      cells revealed hepatocyte growth factor (HGF)-induced nuclear colocalization of p
      MET and Top1. Furthermore, activation of the HGF/MET axis enhanced Top1 activity,
      which was abrogated by SU11274. Combination of SN-38 with SU11274 dramatically
      decreased SCLC growth as compared with either drug alone. Collectively, these
      findings suggest that the combinatorial inhibition of MET and Top1 is a
      potentially efficacious treatment strategy for SCLC.

PMID- 24327521
TI  - Microscopic signature of metallic state in semicrystalline conjugated polymers
      doped with fluoroalkylsilane molecules.
AB  - Fluoroalkylsilane (FTS) acts as an efficient p-type dopant for organic
      semiconductors. FTS-doped films of the semicrystalline PBTTT polymer exhibit
      relatively high conductivities. We demonstrate that highly doped PBTTT films
      exhibit a metallic nature with clear Pauli paramagnetism as observed
      microscopically using electron spin resonance spectroscopy. The metallic state is
      realized within crystalline grains, as confirmed from the anisotropy of the ESR
      signal. 

PMID- 24327522
TI  - CoQ10 and L-carnitine attenuate the effect of high LDL and oxidized LDL on
      spermatogenesis in male rats.
AB  - BACKGROUND: It is estimated that one-third of infertility cases are due to male
      factors. Hyper-cholesterolemia is a social problem in many developed countries
      and contributed with a heterogeneous group of disorders characterized by an
      excess of cholesterol and its derivatives in the blood stream. PURPOSE: The
      objective of the present study was to investigate the protective effects of
      coenzyme Q10 and L-Carnitine supplementation on semen parameters, sperm function
      and reproductive hormone profiles in male Wistar rats with high LDL and Oxidized
      LDL (OxLDL) blood levels. METHODS: Animals were fed with cholesterol and oxidized
      cholesterol-rich diets for 14 weeks to elevate the LDL and OxLDL blood level,
      respectively. Pretreatment with coenzyme Q10 (10 mg/kg/day, oral) and L-Carnitine
      (350 mg/kg/day, oral) were conducted for 5 consecutive weeks. Sex hormones
      levels, malondialdehyde and total antioxidant concentrations, as well as testis,
      epididymis and seminal vesicle weight were also analyzed. RESULTS: Following high
      LDL and OxLDL blood levels, decrease in the sperms count and viability, weights
      of testis, epididymis and seminal vesicle as well as concentration of
      testosterone and LH hormone were observed. On the other hand, in contrast to
      reduction of total antioxidant level, malondialdehyde concentration, both in
      serum and testis, was increased. However, pretreatment with L-carnitine and
      coenzyme Q10 increased serum sex hormones level and improved semen parameters
      significantly. CONCLUSION: Overall, pretreatment with coenzyme Q10 and L
      Carnitine attenuated the destructive effects of high LDL and oxidized LDL levels
      on spermatogenesis parameters in male rats.

PMID- 24327523
TI  - Sampling intervals verification in pharmacokinetics studies.
AB  - Regulatory agencies do not specify how to plan the sampling intervals in
      pharmacokinetics (PK) studies. Every interval between each sampling point forms
      one of the fractions of the area under the curve (AUC). The aim of this study is
      to propose a method of qualitative evaluation of PK studies, on the basis of the
      analysis of the partial AUC fields' values. For the pharmacokinetic analysis,
      average concentrations of high variability drug-itraconazole were used before
      (BO) and after sampling intervals optimization (AO). PK calculations were
      performed using Phoenix(TM) WinNonlin 6.3((r)) (Certara L.P.) and in house
      software Biokinetica 4.0. Arithmetic formula and acceptance limit (AL%) was
      established, below which the mean of partial fields (MAF) value in PK study can
      be considered optimal. In case of MAF the CV% value before optimization was
      125.35 and after the optimization 46.51. In the cases of AUC fractions for
      several partial fields BO data, the AL% value was exceeded. The values of AUC
      fractions did not exceed AL% established for AO data. The paper proposes an
      empirical method of quality assessment, made on the basis of the percentage of
      the AUC fractions. This method can be used in the quality assessment of PK
      studies. 

PMID- 24327524
TI  - Pretreatment neutrophil-to-lymphocyte ratio as predictor of survival for patients
      with metastatic nasopharyngeal carcinoma.
AB  - BACKGROUND: The outcomes of patients with metastatic nasopharyngeal carcinoma
      (NPC) differ between individuals. The purpose of this study was to examine the
      impact of neutrophil-to-lymphocyte ratio (NLR) on survival in patients with
      metastatic NPC. METHODS: A total of 229 patients with disseminated NPC were
      evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte,
      and NLR on survival were examined using the proportional hazards regression model
      to estimate hazard ratio (HR). The relationship between short-term treatment
      efficacy and pretreatment NLR was analyzed using the chi-square test. RESULTS:
      The pretreatment elevated neutrophil count (p = .020), percentage of neutrophil
      (p < .001), and NLR (p = .002) were statistically significantly associated with a
      poor prognosis. The cutoff value selected for NLR was 3.6. The median survival
      time was 15.3 months for the high-NLR group and was 23.5 months for the low-NLR
      group (p < .001). CONCLUSION: NLR is a prognosticator in patients with metastatic
      NPC.

PMID- 24327525
TI  - A novel approach in extracorporeal circulation: individual, integrated, and
      interactive heart-lung assist (I3-Assist).
AB  - Extracorporeal life support (ECLS) is a well-established technique for the
      treatment of different cardiac and pulmonary diseases, e.g., congenital heart
      disease and acute respiratory distress syndrome. Additionally, severely ill
      patients who cannot be weaned from the heart-lung machine directly after surgery
      have to be put on ECLS for further therapy. Although both systems include
      identical components, a seamless transition is not possible yet. The adaption of
      the circuit to the patients' size and demand is limited owing to the components
      available. The project I3-Assist aims at a novel concept for extracorporeal
      circulation. To better match the patient's therapeutic demand of support, an
      individual number of one-size oxygenators and heat exchangers will be combined. A
      seamless transition between cardiopulmonary bypass and ECLS will be possible as
      well as the exchange of components during therapy to enhance circuit maintenance
      throughout long-term support. Until today, a novel oxygenator and heat exchanger
      along with a simplified manufacturing protocol have been established. The first
      layouts of the unit to allow the spill- and bubble-free connection and
      disconnection of modules as well as improved cannulas and a rotational pump are
      investigated using computational fluid dynamics. Tests were performed according
      to current guidelines in vitro and in vivo. The test results show the feasibility
      and potential of the concept.

PMID- 24327526
TI  - Methylation of OPCML promoter in ovarian cancer tissues predicts poor patient
      survival.
AB  - BACKGROUND: Ovarian cancer is a lethal gynecological malignancy largely due to
      the lack of biomarkers for early detection and treatment options. Opioid binding
      protein/cell adhesion molecule-like gene (OPCML) has a tumor-suppressor function
      in ovarian cancer, and epigenetic inactivation of OPCML induces oncogenic
      transformation of human ovarian surface epithelial cells. METHODS: This study
      investigated OPCML promoter methylation levels in ovarian cancer tissues. A total
      of 30 normal ovarian, 85 benign ovarian tumor, and 102 ovarian cancer tissues
      were subjected to quantitative methylation-specific PCR analysis of OPCML
      methylation. Four ovarian cancer cell lines were cultured and treated with the
      DNA demethylation agent 5-aza-2'-deoxycytidine (5-AZA) for restoring OPCML
      expression. RESULTS: The data showed that 80 of 102 (78.4%) ovarian cancer
      tissues and 28 of 85 (32.9%) benign ovarian tumors had a methylated OPCML gene
      promoter. In contrast, there was no OPCML gene promoter methylation in any of the
      30 normal ovarian samples. OPCML promoter methylation was significantly
      associated with an older age of the patients (p=0.022), an advanced pathological
      stage of ovarian cancer (p=0.023), and poor overall survival of ovarian cancer
      patients (p<0.001). Multivariate analysis data showed that pathological stage,
      age, and OPCML promoter methylation were all independent factors to predict
      overall survival of patients. Furthermore, 5-AZA was able to restore expression
      of OPCML mRNA and protein in ovarian cancer cell lines. CONCLUSIONS: These data
      indicate that detection of OPCML gene promoter methylation could be a useful
      biomarker for predicting the prognosis of ovarian cancer patients and disease
      progression.

PMID- 24327527
TI  - Extensive elevation of BNP but not NT-ProBNP in a patient with advanced
      urothelial carcinoma in absence of cardiac failure and volume overload.

PMID- 24327528
TI  - Effect of biobanking conditions on short-term stability of biomarkers in human
      serum and plasma.
AB  - BACKGROUND: Liquid biobanking is an important tool for laboratory diagnostics in
      routine settings and clinical studies. However, the current knowledge about
      adequate storage conditions for different classes of biomarkers is incomplete
      and, in part, contradictory. Here, we performed a comprehensive study on the
      effects of different storage conditions on the stability of various biomarkers in
      human serum and plasma. METHODS: Serum and citrated plasma were aliquoted and
      stored at 4  degrees C, -20  degrees C, -80  degrees C, and <-130  degrees C for
      0, 7, 30, and 90 days, respectively (5-10 pools/condition). Additionally, frozen
      aliquots were temporarily exposed to higher temperatures during storage to
      simulate removing individual samples. Stability was tested for 32 biomarkers from
      10 different parameter classes (electrolytes, enzymes, metabolites, inert
      proteins, complement factors, ketone bodies, hormones, cytokines, coagulation
      factors, and sterols). RESULTS: Biobanking at -80  degrees C and <-130  degrees C
      for up to 90 days did not lead to substantial changes (defined as >3 interassay
      coefficients of variation and p<0.01) of any biomarker concentration. In
      contrast, storage at 4  degrees C and -20  degrees C induced substantial changes
      in single biomarker concentrations in most classes. Such substantial changes were
      increases (<20%) in electrolytes, metabolites, and proteins, and decreases (<96%)
      in enzymes, ketone bodies, cytokines, and coagulation factors. Biomarker
      stability was minimally affected by occasional short-term thermal exposure.
      CONCLUSIONS: Based on these results, we provide recommendations for storage
      conditions of up to 90 days for several biomarkers. Generally, storage at <=-80 
      degrees C for at least 90 days including occasional short-term thermal exposure
      is an excellent storage condition for most biomarkers.

PMID- 24327529
TI  - Analysis of patients with gamma-heavy chain disease by the heavy/light chain and
      free light chain assays.
AB  - BACKGROUND: The objective of this study was to evaluate the performance of the
      heavy/light chain and free light chain immunoassays in patients with heavy chain
      disease, and to assess the ability of the heavy/light chain assay to measure and
      confirm the abnormal, truncated heavy chain. METHODS: Frozen serum samples from
      15 gamma-heavy chain disease patients were tested for IgGkappa, IgGlambda, total
      IgG, free light chains, and M-spike concentrations. RESULTS: The
      (Gkappa+Glambda)/IgGtotal ratio for these 15 patients ranged from 0.02 to 0.80.
      The 10 patients with IgG concentrations above 1 g/dL all had ratios below 0.3
      indicating that a substantial portion of IgG was not quantitated by the Gkappa
      and Glambda reagents. The average M-spike was 1.61 g/dL and the average
      calculated abnormal gamma-chain concentration was 2.94 g/dL. Additionally, free
      light chain analysis revealed the presence of monoclonal free kappa light chain
      in three of the 15 patients. CONCLUSIONS: This study demonstrates utility of a
      nephelometric assay to identify truncated immunoglobulin heavy chains in gamma
      HCD and that 20% of these patients also have monoclonal free light chain.

PMID- 24327530
TI  - Fetal membranes as a source of stem cells.
AB  - In recent years, a constant growth of knowledge and clinical applications of stem
      cells have been observed. Mesenchymal stromal cells, also described as
      mesenchymal stem cells (MSCs) represent a particular cell type for research and
      therapy because of their ability to differentiate into mesodermal lineage cells.
      The most investigated source of MSCs is bone marrow (BM). Yet, collection of BM
      is an invasive procedure associated with significant discomfort to the patient.
      The procedure results in a relatively low number of these cells, which can
      decrease with donor's age. Therefore, it seems to be very important to find other
      sources of mesenchymal stem cells nowadays. A human placenta, which is routinely
      discarded postpartum, in spite of its natural aging process, is still a rich
      source of stem cells capable to proliferate and in vitro differentiate in many
      directions. Besides homing and differentiation in the area of injury, MSCs there
      elicit strong paracrine effects stimulating the processes of repair. In this
      review, we focus on the biology, characteristics and potential clinical
      applications of cells derived from human fetal membranes: amnion and chorion.

PMID- 24327531
TI  - Metformin treatment may be associated with decreased levels of NT-proBNP in
      patients with type 2 diabetes.
AB  - PURPOSE: Individuals with type 2 diabetes (T2DM) are at increased risk of
      cardiovascular disease, including heart failure (HF). In patients with T2DM
      elevated serum concentrations of the N-terminal fragment of pro-B-type
      natriuretic peptide (NT-proBNP) correlate with cardiovascular morbidity and
      mortality. We aimed to identify predictors of increased serum NT-proBNP levels in
      patients with T2DM. METHODS: The study included 185 patients with T2DM treated
      with either oral antidiabetic agents (49.7%) or insulin (17.8%), or both (32.5%).
      We divided the patients into two groups: with high (>200 pg/mL) and low (<=200
      pg/mL) NT-proBNP concentrations. RESULTS: We found differences between the
      patients with high and low NT-proBNP levels including age, prevalence of
      dyslipidemia and HF, history of previous myocardial infarction (MI), heart rate,
      hemoglobin level, platelet count, creatinine, urea and uric acid concentrations,
      use of beta-blockers, loop diuretics, metformin and insulin. In a multivariate
      analysis metformin was a negative predictor of increased NT-proBNP concentration.
      Age, history of HF and decreased estimated glomerular filtration rate (eGFR) were
      positive predictors. We found no correlation between NT-proBNP serum
      concentration and insulin treatment or history of coronary artery disease or MI.
      CONCLUSION: Metformin correlates with lower concentrations of NT-proBNP in
      patients with T2DM.

PMID- 24327532
TI  - The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and
      aldehyde dehydrogenase in ovarian cancer and ovarian cysts.
AB  - PURPOSE: The metabolism of cancerous cells is in many ways different than in
      healthy cells. In ovarian cancer, cells exhibit activity of alcohol dehydrogenase
      (ADH) and aldehyde dehydrogenase (ALDH), which participate in metabolism of many
      biological substances. The aim of this study was to compare the metabolism of
      ovarian cancer cells, ovarian cysts and normal ovarian cells by measurement of
      ADH isoenzymes and ALDH activities. MATERIAL AND METHODS: The study material
      consisted of 36 cancerous ovarian tissues. Class III, IV of ADH and total ADH
      activity was measured by the photometric method and class I, II ADH and ALDH
      activity by the fluorometric method with class-specific fluorogenic substrates.
      RESULTS: The activity of the class I ADH isoenzyme and the total ADH was
      significantly higher in ovarian cancer as compared to ovarian cysts and healthy
      tissues but there are no significant differences between ovarian cysts and
      healthy cells. The other classes of ADH tested, did not show significant
      differences between activity of cancerous cells and healthy ovary. CONCLUSION:
      The increased activity of total ADH in ovarian cancer, especially the class I
      isoenzyme and normal activity of ALDH, may be the factor for the disturbances in
      important biological substances metabolism and could increase the concentration
      of highly carcinogenic acetaldehyde.

PMID- 24327533
TI  - Coronoid-condylar index in assessing of mandibular coronoid hyperplasia.
      Preliminary results.
AB  - PURPOSE: The purpose of this study was to define the coronoid-condylar index
      (CCI). MATERIALS AND METHODS: The material for studies comprised 26 patients.
      Thirteen patients were treated for bilateral coronoid hyperplasia. The remaining
      13 patients were included in the control group. Based on 3D CT measurements, the
      coronoidcondylar index (CCI) was calculated and assessed statistically. RESULTS:
      In patients with coronoid hyperplasia mean CCI was 1.25, while in the control
      group it was 1.00. CONCLUSION: The proposed CCI can be used for the evaluation of
      anomalies of the mandibular coronoid processes.

PMID- 24327535
TI  - Questions about efficacy of exon-skipping therapy for duchenne muscular
      dystrophy.

PMID- 24327534
TI  - Pollen limitation and reduced reproductive success are associated with local
      genetic effects in Prunus virginiana, a widely distributed self-incompatible
      shrub.
AB  - BACKGROUND AND AIMS: A vast quantity of empirical evidence suggests that
      insufficient quantity or quality of pollen may lead to a reduction in fruit set,
      in particular for self-incompatible species. This study uses an integrative
      approach that combines field research with marker gene analysis to understand the
      factors affecting reproductive success in a widely distributed self-incompatible
      species, Prunus virginiana (Rosaceae). METHODS: Twelve patches of P. virginiana
      distributed within three populations that differed in degree of disturbance were
      examined. Two of the sites were small (7-35 km(2)) remnants of forest in an
      intensively used agricultural landscape, while the third was continuous (350
      km(2)) and less disturbed. Field studies (natural and hand cross-pollinations)
      were combined with marker gene analyses (microsatellites and S-locus) in order to
      explore potential factors affecting pollen delivery and consequently reproductive
      success at landscape (between populations) and fine scales (within populations).
      KEY RESULTS: Reductions in reproductive output were found in the two fragments
      compared with the continuous population, and suggest that pollen is an important
      factor limiting fruit production. Genetic analyses carried out in one of the
      fragments and in the continuous site suggest that even though S-allele diversity
      is high in both populations, the fragment exhibits an increase in biparental
      inbreeding and correlated paternity. The increase in biparental inbreeding in the
      fragment is potentially attributable to variation in the density of individuals
      and/or the spatial distribution of genotypes among populations, both of which
      could alter mating dynamics. CONCLUSIONS: By using a novel integrative approach,
      this study shows that even though P. virginiana is a widespread species,
      fragmented populations can experience significant reductions in fruit set and
      pollen limitation in the field. Deatiled examination of one fragmented population
      suggests that these linitations may be explained by an increase in biparental
      inbreeding, correlated paternity and fine-scale genetic structure. The
      consistency of the field and fine-scale genetic analyses, and the consistency of
      the results within patches and across years, suggest that these are important
      processes driving pollen limitation in the fragment.

PMID- 24327536
TI  - Simultaneous determination of some dihydroxybenzenesulphonic acid derivatives and
      their degradation product and main impurity (hydroquinone) by ion-pair liquid
      chromatography.
AB  - A simple and sensitive high-performance liquid chromatography method was
      developed and validated for the determination of calcium dobesilate (DOB) or
      ethamsylate (ETM) in the presence of their degradation product, hydroquinone
      (HQ). The analyses were carried out on Promosil C18 column (4.6 mM * 250 mM, 5 um
      particle size) using an ion-pair mobile phase consisting of methanol-1.5 mM tetra
      butyl ammonium bromide in 0.06 M phosphate buffer (25 : 75, v/v) at pH 6.0 with
      fluorescence detection at 286/333 nm. Pindolol was used as an internal standard.
      The proposed method was found to be rectilinear over the concentration ranges of
      0.05-0.5 ug/mL for DOB, 0.1-0.8 ug/mL for ETM and 0.005-0.1 ug/mL for HQ. The
      method was applied for the determination of the studied drugs in different dosage
      forms and biological fluids. The results of the proposed method were
      statistically compared with those obtained by the comparison methods revealing no
      significance differences in the performance of the methods regarding accuracy and
      precision. Moreover, applying a time-programmed fluorescence technique was
      valuable for the detection of trace amounts of HQ as an impurity and allowed
      purity testing of ETM or DOB within the BP pharmacopeial limit (0.1%).

PMID- 24327537
TI  - An improved highly sensitive method to determine low oxyresveratrol
      concentrations in rat plasma and its pharmacokinetic application.
AB  - Existing methods to determine oxyresveratrol, a trans-polyphenolic stilbene, lack
      selectivity, require large plasma sample volumes or have time-consuming sample
      preparation and chromatographic isolation. Here an improved highly sensitive
      liquid chromatography-tandem mass spectrometry method was developed to determine
      low oxyresveratrol concentrations in rat plasma. The plasma samples were prepared
      by liquid-liquid extraction with acetoacetate. The analytes were separated on
      Venusil hydrophilic interaction chromatography (HILIC) column (2.1 * 50 mm, 5.0
      um) guarded by a HILIC column (4 * 3.0 mm, 5.0 um). The mobile phase consisted of
      acetonitrile-water (containing 1 mmol/L ammonium formate) at gradient elution
      mode with a flow rate of 0.3 mL/min. Resveratrol was used as the internal
      standard. An electrospray ionization source was applied and operated in the
      negative multiple reaction monitoring (MRM) mode. Oxyresveratrol and resveratrol
      were detected on MRM by the transitions from the precursor to the product ion
      (m/z 243.1 -> 175.1 and 227.1 -> 143.0). The total running time was 5 min and the
      retention times of oxyresveratrol and resveratrol were 1.97 and 1.82 min.
      Chromatograms showed no endogenous interfering peaks with blank samples. The
      linear calibration curve was obtained over the concentration range of 1-500
      ng/mL. The injection volume was 10 MUL and the limit of quantification was 1
      ng/mL. The extraction recovery varied from 78.2 to 84.3% for low, medium and high
      quality control samples. At the same time, the intra- and inter-day relative
      standard deviations were <6.78 and <10.02%, respectively, while the corresponding
      intra- and inter-day accuracy relative error values fell in the range of 3.75
      6.67%. The HPLC-MS/MS method was successfully applied to a pharmacokinetics
      study, in which the experimental rats received a single dose of oxyresveratrol
      (10 mg/kg, intragastric administration). The pharmacokinetic results are
      presented.

PMID- 24327538
TI  - In vivo exposure to benzo(a)pyrene induces significant DNA damage in mouse
      oocytes and cumulus cells.
AB  - STUDY QUESTION: Does in vivo exposure to benzo(a)pyrene (BaP) induce DNA damage
      in oocytes and cumulus cells (CCs) in mice? SUMMARY ANSWER: Significant increases
      in DNA strand breaks in oocytes and CCs and in BaP-induced DNA adducts in CCs
      were detected in exposed mice compared with controls. WHAT IS KNOWN ALREADY: BaP
      has well-known mutagenic and carcinogenic effects on somatic cells, and is also
      registered as potential reproductive toxicant by several environmental protection
      agencies. It has been shown to cause a significant increase in DNA adducts in
      ovarian tissues; however, to our knowledge, the genotoxic effects of BaP on
      oocytes and CCs have not been studied to date. STUDY DESIGN, SIZE, DURATION:
      Female CD1 mice were exposed to BaP via the oral administration of a single dose
      of 13 mg/kg body weight (bw); matched controls were exposed to the vehicle only
      (soya oil). A total of 15 groups of 6 mice (exposed or controls) were sacrificed
      2, 4, 6, 15 or 22 days after BaP exposure, and after collection of oviducts, the
      oocyte-CC complexes (COC) were released. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: The alkaline comet assay was used to quantify the DNA breaks in oocytes
      and CCs; DNA damage was expressed as the Olive Tail Moment (OTM).
      Immunofluorescent staining was used to quantify BaP-induced DNA adducts in CCs.
      Fluorescence was expressed as the average grey value (AGVA; arbitrary units). The
      differences between the exposed and control groups were assessed using analysis
      of variance (ANOVA) and the non-parametric Mann-Whitney test. MAIN RESULTS AND
      THE ROLE OF CHANCE: Higher levels of DNA damage were observed in the oocytes and
      CCs of BaP-exposed mice than in those of vehicle controls. Significant increases
      in OTM (mean +/- SE) were detected in (i) oocytes from females exposed for 4
      (10.5 +/- 0.9 versus 3.1 +/- 0.4, P < 0.0001) or 6 days before collection (15.6
      +/- 2.0 versus 3.6 +/- 0.9, P < 0.0001) and (ii) CCs from females exposed 2 (6.4
      +/- 0.6 versus 2.1 +/- 0.2, P < 0.0001), 4 (7.8 +/- 0.4 versus 2.4 +/- 0.1, P <
      0.0001) or 6 days before collection (7.3 +/- 0.3 versus 3.2 +/- 0.5, P < 0.0001)
      compared with controls. A significant increase in benzo(a)pyrene-7,8-9,10 diol
      epoxide (BPDE)-DNA adducts and higher AGVA (mean +/- SE) scores were observed in
      CCs from females exposed 2 (6.1 +/- 0.3 versus 3.6 +/- 0.5, P < 0.0001), 4 (7.5
      +/- 0.1 versus 3.4 +/- 0.1, P < 0.0001) or 6 days before collection (11.6 +/- 0.4
      versus 3.7 +/- 0.1, P < 0.0001) compared with control mice. LIMITATIONS, REASONS
      FOR CAUTION: Mice were given one treatment via the oral route because this dose
      and mode of administration have been shown to induce detectable BPDE-DNA adduct
      levels in mouse organs and sperm cells. Additional data are needed to assess DNA
      damage in oocytes and CCs after chronic exposure to BaP in vivo. WIDER
      IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study examining
      the in vivo genotoxicity of BaP in oocytes and CCs. We observed significant DNA
      damage in the oocytes and CCs of mice after acute BaP exposure. BPDE-DNA adducts
      result directly from BaP metabolism while DNA breaks could result mainly from
      BPDE-DNA adduct excision and repair and/or through direct genotoxicity from
      increased reactive oxygen species. These results add new and important insights
      regarding the recently suggested toxicity of chronic BaP exposure in the ovary.
      STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant (93-CPQ
      2012-05) from the DIRRECTE, Provence Alpes Cote d'Azur, France. None of the
      authors have any conflict of interest to declare.

PMID- 24327539
TI  - First pregnancy and live birth resulting from cryopreserved embryos obtained from
      in vitro matured oocytes after oophorectomy in an ovarian cancer patient.
AB  - In vitro maturation (IVM) of immature oocytes retrieved from surgically resected
      ovaries has been proposed as a method of fertility preservation in ovarian cancer
      patients undergoing definitive surgery. While there had been several reports of
      successful derivation of mature oocytes and or embryos, there have been no
      reports as yet of successful pregnancies. In this case report, we present a
      pregnancy and live birth from a young patient, with stage IIIC ovarian cancer,
      who had undergone fertility sparing surgery. The immature oocytes recovered after
      oophorectomy were fertilized after IVM. The embryos obtained were cryopreserved
      and later transferred to achieve a singleton healthy pregnancy leading to a live
      birth. 

PMID- 24327540
TI  - Thermodynamics of water-solid interactions in crystalline and amorphous
      pharmaceutical materials.
AB  - Pharmaceutical materials, crystalline and amorphous, sorb water from the
      atmosphere, which affects critical factors in the development of drugs, such as
      the selection of drug substance crystal form, compatibility with excipients,
      dosage form selection, packaging, and product shelf-life. It is common practice
      to quantify the amount of water that a material sorbs at a given relative
      humidity (RH), but the results alone provide minimal to no physicochemical
      insight into water-solid interactions, without which pharmaceutical scientists
      cannot develop an understanding of their materials, so as to anticipate and
      circumvent potential problems. This research was conducted to advance the science
      of pharmaceutical materials by examining the thermodynamics of solids with sorbed
      water. The compounds studied include nonhygroscopic drugs, a channel hydrate
      drug, a stoichiometric hydrate excipient, and an amorphous excipient. The water
      sorption isotherms were measured over a range of temperature to extract the
      partial molar enthalpy and entropy of sorbed water as well as the same quantities
      for some of the solids. It was found that water-solid interactions spanned a
      range of energy and entropy as a function of RH, which was unique to the solid,
      and which could be valuable in identifying batch-to-batch differences and effects
      of processing in material performance.

PMID- 24327541
TI  - The role of topoisomerase II beta on breakage and proximity of RUNX1 to partner
      alleles RUNX1T1 and EVI1.
AB  - Rearrangements involving the RUNX1 gene account for approximately 15% of balanced
      translocations in therapy-related acute myeloid leukemia (t-AML) patients and are
      one of the most common genetic abnormalities observed in t-AML. Drugs targeting
      the topoisomerase II (TOP2) enzyme are implicated in t-AML; however, the
      mechanism is not well understood and to date a single RUNX1-RUNX1T1 t-AML
      breakpoint junction sequence has been published. Here we report an additional
      five breakpoint junction sequences from t-AML patients with the RUNX1- RUNX1T1
      translocation. Using a leukemia cell line model, we show that TOP2 beta (TOP2B)
      is required for induction of RUNX1 chromosomal breaks by the TOP2 poison
      etoposide and that, while TOP2 alpha (TOP2A) and TOP2B proteins are both present
      on RUNX1 and RUNX1T1 chromatin, only the TOP2B enrichment reached significance
      following etoposide exposure at a region on RUNX1 where translocations occur.
      Furthermore, we demonstrate that TOP2B influences the separation between RUNX1
      and two translocation partners (RUNX1T1 and EVI) in the nucleus of lymphoid
      cells. Specifically, we identified a TOP2B-dependent increase in the number of
      nuclei displaying juxtaposed RUNX1 and RUNX1T1 loci following etoposide
      treatment.

PMID- 24327543
TI  - Targetable activating mutations are very frequent in GCB and ABC diffuse large B
      cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is an aggressive and heterogeneous
      malignancy that can be divided in two major subgroups, germinal center B-cell
      like (GCB) and activated B-cell-like (ABC). Activating mutations of genes
      involved in the BCR and NF-kappaB pathways (CD79A, CD79B, MYD88, and CARD11) or
      in epigenetic regulation (EZH2) have been recently reported, preferentially in
      one of the two DLBCL subtypes. We analyzed the mutational status of these five
      recurrently mutated genes in a cohort of 161 untreated de novo DLBCL. Overall, 93
      mutations were detected, in 61 (38%) of the patients. The L265P MYD88 mutation
      was the most frequent MYD88 variant (n = 18), observed exclusively in the ABC
      subtype. CD79A/CD79B ITAM domains were targeted in ABC DLBCL (12/77; 16%),
      whereas CARD11 mutations were equally distributed in the two subtypes. The EZH2
      Y641 substitution was found almost exclusively in the GCB subgroup (15/62; 24%).
      Twenty cases (12%) displayed two activating mutations, including the most
      frequent CD79/MYD88 variants combination (n = 8) which is observed exclusively in
      the ABC subtype. When considering only ABC DLBCL patients treated by rituximab
      plus chemotherapy, the presence of an activating NF-kappaB mutation was
      associated with an unfavorable outcome (3-years OS 26% for mutated cases versus
      67% for the cases without mutations, P = 0.0337). Our study demonstrates that
      activating and targetable mutations are observed at a very high frequency in
      DLBCL at the time of diagnosis, indicating that sequencing of a limited number of
      genes could help tailor an optimal treatment strategy in DLBCL.

PMID- 24327542
TI  - Targeted inhibition of ATR or CHEK1 reverses radioresistance in oral squamous
      cell carcinoma cells with distal chromosome arm 11q loss.
AB  - Oral squamous cell carcinoma (OSCC), a subset of head and neck squamous cell
      carcinoma (HNSCC), is the eighth most common cancer in the U.S.. Amplification of
      chromosomal band 11q13 and its association with poor prognosis has been well
      established in OSCC. The first step in the breakage-fusion-bridge (BFB) cycle
      leading to 11q13 amplification involves breakage and loss of distal 11q. Distal
      11q loss marked by copy number loss of the ATM gene is observed in 25% of all
      Cancer Genome Atlas (TCGA) tumors, including 48% of HNSCC. We showed previously
      that copy number loss of distal 11q is associated with decreased sensitivity
      (increased resistance) to ionizing radiation (IR) in OSCC cell lines. We
      hypothesized that this radioresistance phenotype associated with ATM copy number
      loss results from upregulation of the compensatory ATR-CHEK1 pathway, and that
      knocking down the ATR-CHEK1 pathway increases the sensitivity to IR of OSCC cells
      with distal 11q loss. Clonogenic survival assays confirmed the association
      between reduced sensitivity to IR in OSCC cell lines and distal 11q loss. Gene
      and protein expression studies revealed upregulation of the ATR-CHEK1 pathway and
      flow cytometry showed G2 M checkpoint arrest after IR treatment of cell lines
      with distal 11q loss. Targeted knockdown of the ATR-CHEK1 pathway using CHEK1 or
      ATR siRNA or a CHEK1 small molecule inhibitor (SMI, PF-00477736) resulted in
      increased sensitivity of the tumor cells to IR. Our results suggest that distal
      11q loss is a useful biomarker in OSCC for radioresistance that can be reversed
      by ATR-CHEK1 pathway inhibition.

PMID- 24327544
TI  - Molecular events underlying interleukin-6 independence in a subclone of the CMA
      03 multiple myeloma cell line.
AB  - We explored the molecular mechanisms involved in the establishement of CMA-03/06,
      an IL-6-independent variant of the multiple myeloma cell line CMA-03 previously
      generated in our Institution. CMA-03/06 cells grow in the absence of IL-6 with a
      doubling time comparable with that of CMA-03 cells; neither the addition of IL6
      (IL-6) to the culture medium nor co-culture with multipotent mesenchymal stromal
      cells increases the proliferation rate, although they maintain the responsiveness
      to IL-6 stimulation as demonstrated by STAT1, STAT3, and STAT5 induction. IL-6
      independence of CMA-03/06 cells is not apparently due to the development of an
      autocrine IL-6 loop, nor to the observed moderate constitutive activation of
      STAT5 and STAT3, since STAT3 silencing does not affect cell viability or
      proliferation. When compared to the parental cell line, CMA-03/06 cells showed an
      activated pattern of the NF-kappaB pathway. This finding is supported by gene
      expression profiling (GEP) analysis identifying an appreciable fraction of
      modulated genes (28/308) in the CMA-03/06 subclone reported to be involved in
      this pathway. Furthermore, although more resistant to apoptotic stimuli compared
      to the parental cell line, CMA-03/06 cells display a higher sensibility to NF
      kappaB inhibition induced by bortezomib. Finally, GEP analysis suggests an
      involvement of a number of cytokines, which might contribute to IL-6 independence
      of CMA-03/06 by stimulating growth and antiapoptotic processes. In conclusion,
      the parental cell-line CMA-03 and its variant CMA-03/06 represent a suitable
      model to further investigate molecular mechanisms involved in the IL-6
      independent growth of myeloma cells.

PMID- 24327545
TI  - SMARCB1 expression in epithelioid sarcoma is regulated by miR-206, miR-381, and
      miR-671-5p on Both mRNA and protein levels.
AB  - Proximal type epithelioid sarcoma shares similarities with malignant rhabdoid
      tumor, including the lack of nuclear immunoreactivity of SMARCB1. Biallelic
      mutation of SMARCB1 has been convincingly established as the cause of loss of
      protein expression in rhabdoid tumor, but the cause in epithelioid sarcoma
      remains unknown. In our previous work, we demonstrated that DNA hypermethylation
      and post-translational modification mechanisms were not involved. In this current
      work, we explored the hypothesis that miRNAs regulate SMARCB1 gene expression in
      epithelioid sarcomas. In silico target prediction analysis revealed eight
      candidate miRNAs, and quantitative PCR-in 32 formalin-fixed, paraffin-embedded
      tumor samples comprising 30 epithelioid sarcomas and two malignant rhabdoid
      tumors-demonstrated significant (P < 0.001) overexpression of four miRNAs in
      epithelioid sarcomas: miR-206, miR-381, miR-671-5p, and miR-765. Two human tumors
      (fibrosarcoma and colon adenocarcinoma) and a normal cell line (human dermal
      fibroblast) with retained SMARCB1 expression were cultured for miRNA transient
      transfection (electroporation) experiments. SMARCB1 mRNA expression was analyzed
      by quantitative real-time PCR and immunostaining of SMARCB1 was performed to
      examine the effect of miRNAs transfections on both RNA and protein levels. Only
      three of the overexpressed miRNAs (miR-206, miR-381, and miR-671-5p) could
      silence the SMARCB1 mRNA expression in cell cultures; most effectively miR-206.
      Transfection of miR-206, miR-381, miR-671-5p, and some combination of them also
      eliminated SMARCB1 nuclear staining, demonstrating a strong effect on not only
      mRNA but also protein levels. Our results suggest loss of SMARCB1 protein
      expression in epithelioid sarcoma is due to the epigenetic mechanism of gene
      silencing by oncomiRs.

PMID- 24327547
TI  - Relaxation effects in MRI-based quantification of fat content and fatty acid
      composition.
AB  - PURPOSE: To investigate various sources of bias in MRI-based quantification of
      fat fraction (FF) and fatty acid composition (FAC) using chemical shift-encoded
      techniques. METHODS: Signals from various FFs and FACs and individual relaxation
      rates of all signal components were simulated. From these signals, FF and FAC
      parameters were estimated with and without correction for differences in
      individual relaxation rates. In addition, phantom experiments were conducted with
      various flip angles and number of echoes to validate the simulations. RESULTS: As
      expected, T(1) weighting resulted in an overestimation of the FF, but had much
      smaller impact on the FAC parameters. Differences in T(2) values of the signal
      components resulted in overestimation of the FAC parameters in fat/water
      mixtures, whereas the estimation in pure oil was largely unaffected. This bias
      was corrected using a simplified signal model with different T(2) values of water
      and fat, where the accuracy of the modeled T(2) of water was critical. The
      results of the phantom experiment were in agreement with simulations. CONCLUSION:
      T(1) weighting has only a minor effect on FAC quantification in both fat/water
      mixtures and pure oils. T(2) weighting is mainly a concern in fat/water mixtures
      but may be corrected using a simplified model.

PMID- 24327546
TI  - Corrections for mRNA extraction and sample normalization errors find increased
      mRNA levels may compensate for cancer haplo-insufficiency.
AB  - The relative mRNA levels of differentially expressed (DE) and housekeeping (HK)
      genes of six aneuploid cancer lines with large-scale genomic changes identified
      by SNP/SKY analysis were compared with similar genes in diploid cells. The
      aneuploid cancer lines had heterogeneous genomic landscapes with subdiploid,
      diploid, and supradiploid regions and higher overall gene copy numbers compared
      with diploid cells. The mRNA levels of the haploid, diploid, and triploid HK
      genes were found to be higher after correction of easily identifiable mRNA
      measurement errors. Surprisingly, diploid and aneuploid HK gene mRNA levels were
      the same by standard expression array analyses, despite the higher copy numbers
      of the cancer cell HK genes. This paradoxical result proved to be due to
      inaccurate inputs of true intra-cellular mRNAs for analysis. These errors were
      corrected by analyzing the expression intensities of DE and HK genes in mRNAs
      extracted from equal cell numbers (50:50) of intact cancer cell and lymphocyte
      mixtures. Correction for both mRNA extraction/sample normalization errors and
      total gene copy numbers found the SUIT-2 and PC-3 cell lines' cancer genes both
      had ~50% higher mRNA levels per single allele than lymphocyte gene alleles. These
      increased mRNA levels for single transcribed cancer alleles may restore
      functional mRNA levels to cancer genes rendered haplo-insufficient by the genetic
      instability of cancer. (c) 2013 Wiley Periodicals, Inc.

PMID- 24327548
TI  - Exploring the effect of bioisosteric replacement of carboxamide by a sulfonamide
      moiety on N-glycosidic torsions and molecular assembly: synthesis and X-ray
      crystallographic investigation of N-(beta-D-glycosyl)sulfonamides as N
      glycoprotein linkage region analogues.
AB  - N-Glycoprotein linkage region constituents, 2-acetamido-2-deoxy-beta-D
      glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all the
      eukaryotes. To gain a better understanding for nature's choice of GlcNAcbetaAsn
      as linkage region constituents and inter- and intramolecular carbohydrate-protein
      interactions, a detailed systemic structural study of the linkage region
      conformation is essential. Earlier crystallographic studies of several N-(beta
      glycopyranosyl)alkanamides showed that N-glycosidic torsion, phiN , is influenced
      to a larger extent by structural variation in the sugar part than that of the
      aglycon moiety. To explore the effect of the bioisosteric replacement of a
      carboxamide group by a sulfonamide moiety on the N-glycosidic torsions as well as
      on molecular assembly, several glycosyl methanesulfonamides and glycosyl
      chloromethanesulfonamides were synthesized as analogues of the N-glycoprotein
      linkage region, and crystal structures of seven of these compounds have been
      solved. A comparative analysis of this series of crystal structures as well as
      with those of the corresponding alkanamido derivatives revealed that N-glycosidic
      torsion, phiN, does not alter significantly. Methanesulfonamido and
      chloromethanesulfonamido derivatives of GlcNAc display a different aglycon
      conformation compared to other sulfonamido analogues. This may be due to the
      cumulative effect of the direct hydrogen bonding between N1 and O1' and C-H...O
      interactions of the aglycon chain, revealing the uniqueness of the GlcNAc as the
      linkage sugar.

PMID- 24327549
TI  - Gold nanoparticle loaded hybrid nanofibers for cardiogenic differentiation of
      stem cells for infarcted myocardium regeneration.
AB  - Heart disease is the leading cause of mortality in many industrialized nations
      and is often related to irregularities in electrical function that can radically
      damage cardiac functioning. The aim of this study is to develop a novel
      therapeutic hybrid scaffold that can couple electrical, mechanical, and
      biological properties, desirable for cardiac tissue regeneration. BSA/PVA
      scaffolds are fabricated in the ratio 2:1 and gold nanoparticles (AuNPs) embedded
      scaffolds in the ratios BSA/PVA/Au of 2:1:0.1 (lower concentration) and
      BSA/PVA/Au of 2:1:0.4 (higher concentration) by electrospinning. The scaffolds
      are characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), contact angle, Fourier transform infrared (FTIR) spectroscopy,
      and tensile testing to analyze the fiber morphology, AuNP distribution,
      hydrophilicity, surface functional groups, and mechanical properties of the
      scaffolds, respectively. Results show that ex vivo pretreatment of MSCs using 5
      aza and AuNPs loaded conductive nanofibrous construct could lead to enhanced
      cardiomyogenic differentiation and result in superior biological and functional
      effects on infarcted myocardium regeneration.

PMID- 24327550
TI  - Human collagen-based multilayer scaffolds for tendon-to-bone interface tissue
      engineering.
AB  - The natural tendon-to-bone region has a gradient in structure and composition,
      which is translated into a spatial variation of chemical, physical, and
      biological properties. This unique transitional tissue between bone and tendon is
      not normally recreated during natural bone-to-tendon healing. In this study, we
      have developed a human collagen-based multilayer scaffold mimicking the tendon-to
      bone region. The scaffold consists of four different layers with the following
      composition gradient: (a) a tendon layer composed of collagen; (b) an uncalcified
      fibrocartilage layer composed of collagen and chondroitin sulfate; (c) a
      calcified fibrocartilage layer composed of collagen and less apatite; (d) a bone
      layer composed of collagen and apatite. The chemical, physical, and mechanical
      properties of the scaffold were characterized by a scanning electron microscope,
      porosimeter, universal tensile machine, Fourier transform infrared spectrometer,
      energy dispersive X-ray analysis apparatus, and thermogravimetric analysis
      apparatus. The multilayer scaffold provided a gradual transition of the physical,
      chemical, and mechanical environment and supported the adhesion and proliferation
      of human fibroblasts, chondrocytes, and osteoblasts toward each corresponding
      matrix. Overall, our results suggest the feasibility of a human collagen-based
      multilayer scaffold for regeneration of hard-to-soft interface tissues.

PMID- 24327551
TI  - Quantification of carbamazepine and its 10,11-epoxide metabolite in rat plasma by
      UPLC-UV and application to pharmacokinetic study.
AB  - A rapid, selective and sensitive UPLC-UV method was developed and validated for
      the quantitative analysis of carbamazepine and its epoxide metabolite in rat
      plasma. A relatively small volume of plasma sample (200 MUL) is required for the
      described analytical method. The method includes simple protein precipitation,
      liquid-liquid extraction, evaporation, and reconstitution steps. Samples were
      separated on a Waters Acquity UPLC BEH C18 column (1.7 um, 2.1 * 100 mm) with a
      gradient mobile phase consisted of 60:40 going to 40:60 (v/v) water-acetonitrile
      at a flow rate of 0.5 mL/min. The total run time was as low as 6 min,
      representing a significant improvement in comparison to existing methods.
      Excellent linearity (r(2)  > 0.999) was achieved over a wide concentration range.
      Close to complete recovery, short analysis time, high stability, accuracy,
      precision and reproducibility, and low limit of quantitation were demonstrated.
      Finally, we successfully applied this analytical method to a pre-clinical oral
      pharmacokinetic study, revealing the plasma profiles of both carbamazepine and
      carbamazepine-10,11-epoxide following oral administration of carbamazepine to
      rats. The advantages demonstrated in this work make this analytical method both
      time- and cost-efficient approach for drug and metabolite monitoring in the pre
      clinical/clinical laboratory.

PMID- 24327552
TI  - Presurgical diagnosis of adnexal tumours using mathematical models and scoring
      systems: a systematic review and meta-analysis.
AB  - BACKGROUND Characterizing ovarian pathology is fundamental to optimizing
      management in both pre- and post-menopausal women. Inappropriate referral to
      oncology services can lead to unnecessary surgery or overly radical interventions
      compromising fertility in young women, whilst the consequences of failing to
      recognize cancer significantly impact on prognosis. By reflecting on recent
      developments of new diagnostic tests for preoperative identification of malignant
      disease in women with adnexal masses, we aimed to update a previous systematic
      review and meta-analysis. METHODS An extended search was performed in MEDLINE
      (PubMed) and EMBASE (OvidSp) from March 2008 to October 2013. Eligible studies
      provided information on diagnostic test performance of models, designed to
      predict ovarian cancer in a preoperative setting, that contained at least two
      variables. Study selection and extraction of study characteristics, types of
      bias, and test performance was performed independently by two reviewers. Quality
      was assessed using a modified version of the QUADAS assessment tool. A bivariate
      hierarchical random effects model was used to produce summary estimates of
      sensitivity and specificity with 95% confidence intervals or plot summary ROC
      curves for all models considered. RESULTS Our extended search identified a total
      of 1542 new primary articles. In total, 195 studies were eligible for qualitative
      data synthesis, and 96 validation studies reporting on 19 different prediction
      models met the predefined criteria for quantitative data synthesis. These models
      were tested on 26 438 adnexal masses, including 7199 (27%) malignant and 19 239
      (73%) benign masses. The Risk of Malignancy Index (RMI) was the most frequently
      validated model. The logistic regression model LR2 with a risk cut-off of 10% and
      Simple Rules (SR), both developed by the International Ovarian Tumor Analysis
      (IOTA) study, performed better than all other included models with a pooled
      sensitivity and specificity, respectively, of 0.92 [95% CI 0.88-0.95] and 0.83
      [95% CI 0.77-0.88] for LR2 and 0.93 [95% CI 0.89-0.95] and 0.81 [95% CI 0.76
      0.85] for SR. A meta-analysis of centre-specific results stratified for
      menopausal status of two multicentre cohorts comparing LR2, SR and RMI-1 (using a
      cut-off of 200) showed a pooled sensitivity and specificity in premenopausal
      women for LR2 of 0.85 [95% CI 0.75-0.91] and 0.91 [95% CI 0.83-0.96] compared
      with 0.93 [95% CI 0.84-0.97] and 0.83 [95% CI 0.73-0.90] for SR and 0.44 [95% CI
      0.28-0.62] and 0.95 [95% CI 0.90-0.97] for RMI-1. In post-menopausal women,
      sensitivity and specificity of LR2, SR and RMI-1 were 0.94 [95% CI 0.89-0.97] and
      0.70 [95% CI 0.62-0.77], 0.93 [95% CI 0.88-0.96] and 0.76 [95% CI 0.69-0.82], and
      0.79 [95% CI 0.72-0.85] and 0.90 [95% CI 0.84-0.94], respectively. CONCLUSIONS An
      evidence-based approach to the preoperative characterization of any adnexal mass
      should incorporate the use of IOTA Simple Rules or the LR2 model, particularly
      for women of reproductive age. 

PMID- 24327553
TI  - PCLR: phase-constrained low-rank model for compressive diffusion-weighted MRI.
AB  - PURPOSE: This work develops a compressive sensing approach for diffusion-weighted
      (DW) MRI. THEORY AND METHODS: A phase-constrained low-rank (PCLR) approach was
      developed using the image coherence across the DW directions for efficient
      compressive DW MRI, while accounting for drastic phase changes across the DW
      directions, possibly as a result of eddy current, and rigid and nonrigid motions.
      In PCLR, a low-resolution phase estimation was used for removing phase
      inconsistency between DW directions. In our implementation, GRAPPA (generalized
      autocalibrating partial parallel acquisition) was incorporated for better phase
      estimation while allowing higher undersampling factor. An efficient and easy-to
      implement image reconstruction algorithm, consisting mainly of partial Fourier
      update and singular value decomposition, was developed for solving PCLR. RESULTS:
      The error measures based on diffusion-tensor-derived metrics and tractography
      indicated that PCLR, with its joint reconstruction of all DW images using the
      image coherence, outperformed the frame-independent reconstruction through zero
      padding FFT. Furthermore, using GRAPPA for phase estimation, PCLR readily
      achieved a four-fold undersampling. CONCLUSION: The PCLR is developed and
      demonstrated for compressive DW MRI. A four-fold reduction in k-space sampling
      could be readily achieved without substantial degradation of reconstructed images
      and diffusion tensor measures, making it possible to significantly reduce the
      data acquisition in DW MRI and/or improve spatial and angular resolutions.

PMID- 24327554
TI  - Fabrication of novel reduction-sensitive gene vectors based on three-armed
      peptides.
AB  - To address the inherent barriers of gene transfection, two reduction-sensitive
      branched polypeptides (RBPs) are synthesized and explored as novel non-viral gene
      vectors. The introduced disulfide linkages in RBPs facilitate glutathione
      triggered intracellular gene release and reduce polymer degradation-induced
      cytotoxicity. Furthermore, the highly branched architecture concurrently realizes
      multivalency for strong DNA binding and elicits conformational flexibility for
      tight DNA compacting, which are beneficial for cellular entry. To increase the
      endosomal escape of plasmid DNA, pH-sensitive histidyl residues are incorporated
      into RBPs to improve buffer capacity in an acidic environment. In vitro study
      demonstrates that RBPs can efficiently mediate the DNA transfection and avoid
      apparent cytotoxicity in HeLa and COS7. The present gene delivery system offers a
      simple and flexible approach to fabricate microenvironment-specific branched gene
      vectors for gene therapy.

PMID- 24327555
TI  - Insertion of a single-molecule magnet inside a ferromagnetic lattice based on a
      3D bimetallic oxalate network: towards molecular analogues of permanent magnets.
AB  - The insertion of the single-molecule magnet (SMM) [Mn(III)(salen)(H2O)]2(2+)
      (salen(2-) = N,N'-ethylenebis-(salicylideneiminate)) into a ferromagnetic
      bimetallic oxalate network affords the hybrid compound
      [Mn(III)(salen)(H2O)]2[Mn(II)Cr(III)(ox)3]2?(CH3OH)?(CH3CN)2 (1). This cationic
      Mn2 cluster templates the growth of crystals formed by an unusual achiral 3D
      oxalate network. The magnetic properties of this hybrid magnet are compared with
      those of the analogous compounds
      [Mn(III)(salen)(H2O)]2[Zn(II)Cr(III)(ox)3]2?(CH3OH)?(CH3CN)2 (2) and
      [In(III)(sal2-trien)][Mn(II)Cr(III)(ox)3]?(H2O)0.25?(CH3OH)0.25?(CH3CN)0.25 (3),
      which are used as reference compounds. In 2 it has been shown that the magnetic
      isolation of the Mn2 clusters provided by their insertion into a paramagnetic
      oxalate network of Cr(III) affords a SMM behavior, albeit with blocking
      temperatures well below 500 mK even for frequencies as high as 160 kHz. In 3 the
      onset of ferromagnetism in the bimetallic Mn(II) Cr(III) network is observed at
      Tc = 5 K. Finally, in the hybrid compound 1 the interaction between the two
      magnetic networks leads to the antiparallel arrangement of their respective
      magnetizations, that is, to a ferrimagnetic phase. This coupling induces also
      important changes on the magnetic properties of 1 with respect to those of the
      reference compounds 2 and 3. In particular, compound 1 shows a large
      magnetization hysteresis below 1 K, which is in sharp contrast with the near
      reversible magnetizations that the SMMs and the oxalate ferromagnetic lattice
      show under the same conditions.

PMID- 24327556
TI  - Award Winner in the Young Investigator Category, 2014 Society for Biomaterials
      Annual Meeting and Exposition, Denver, Colorado, April 16-19, 2014: Periodically
      perforated core-shell collagen biomaterials balance cell infiltration,
      bioactivity, and mechanical properties.
AB  - Orthopedic tissue engineering requires biomaterials with robust mechanics as well
      as adequate porosity and permeability to support cell motility, proliferation,
      and new extracellular matrix (ECM) synthesis. While collagen-glycosaminoglycan
      (CG) scaffolds have been developed for a range of tissue engineering
      applications, they exhibit poor mechanical properties. Building on previous work
      in our lab that described composite CG biomaterials containing a porous scaffold
      core and nonporous CG membrane shell inspired by mechanically efficient core
      shell composites in nature, this study explores an approach to improve cellular
      infiltration and metabolic health within these core-shell composites. We use
      indentation analyses to demonstrate that CG membranes, while less permeable than
      porous CG scaffolds, show similar permeability to dense materials such as small
      intestine submucosa (SIS). We also describe a simple method to fabricate CG
      membranes with organized arrays of microscale perforations. We demonstrate that
      perforated membranes support improved tenocyte migration into CG scaffolds, and
      that migration is enhanced by platelet-derived growth factor BB-mediated
      chemotaxis. CG core-shell composites fabricated with perforated membranes display
      scaffold-membrane integration with significantly improved tensile properties
      compared to scaffolds without membrane shells. Finally, we show that perforated
      membrane-scaffold composites support sustained tenocyte metabolic activity as
      well as improved cell infiltration and reduced expression of hypoxia-inducible
      factor 1alpha compared to composites with nonperforated membranes. These results
      will guide the design of improved biomaterials for tendon repair that are
      mechanically competent while also supporting infiltration of exogenous cells and
      other extrinsic mediators of wound healing.

PMID- 24327557
TI  - Discovery of a metabolic alternative to the classical mevalonate pathway.
AB  - Eukarya, Archaea, and some Bacteria encode all or part of the essential
      mevalonate (MVA) metabolic pathway clinically modulated using statins. Curiously,
      two components of the MVA pathway are often absent from archaeal genomes. The
      search for these missing elements led to the discovery of isopentenyl phosphate
      kinase (IPK), one of two activities necessary to furnish the universal five
      carbon isoprenoid building block, isopentenyl diphosphate (IPP). Unexpectedly, we
      now report functional IPKs also exist in Bacteria and Eukarya. Furthermore,
      amongst a subset of species within the bacterial phylum Chloroflexi, we
      identified a new enzyme catalyzing the missing decarboxylative step of the
      putative alternative MVA pathway. These results demonstrate, for the first time,
      a functioning alternative MVA pathway. Key to this pathway is the catalytic
      actions of a newly uncovered enzyme, mevalonate phosphate decarboxylase (MPD) and
      IPK. Together, these two discoveries suggest that unforeseen variation in
      isoprenoid metabolism may be widespread in nature. DOI:
      http://dx.doi.org/10.7554/eLife.00672.001. 

PMID- 24327558
TI  - Charcot-Marie-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration
      due to partial loss of function.
AB  - The small GTPase Rab7 is a key regulator of endosomal maturation in eukaryotic
      cells. Mutations in rab7 are thought to cause the dominant neuropathy Charcot
      Marie-Tooth 2B (CMT2B) by a gain-of-function mechanism. Here we show that loss of
      rab7, but not overexpression of rab7 CMT2B mutants, causes adult-onset
      neurodegeneration in a Drosophila model. All CMT2B mutant proteins retain 10-50%
      function based on quantitative imaging, electrophysiology, and rescue experiments
      in sensory and motor neurons in vivo. Consequently, expression of CMT2B mutants
      at levels between 0.5 and 10-fold their endogenous levels fully rescues the
      neuropathy-like phenotypes of the rab7 mutant. Live imaging reveals that CMT2B
      proteins are inefficiently recruited to endosomes, but do not impair endosomal
      maturation. These findings are not consistent with a gain-of-function mechanism.
      Instead, they indicate a dosage-dependent sensitivity of neurons to rab7
      dependent degradation. Our results suggest a therapeutic approach opposite to the
      currently proposed reduction of mutant protein function. DOI:
      http://dx.doi.org/10.7554/eLife.01064.001. 

PMID- 24327559
TI  - Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of
      antimicrobial pressure.
AB  - Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a
      severe systemic infection caused by the bacterium Salmonella enterica serovar
      Typhi. FQ-resistance mutations in S. Typhi have become common, hindering
      treatment and control efforts. Using in vitro competition experiments, we assayed
      the fitness of eleven isogenic S. Typhi strains with resistance mutations in the
      FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out
      of 11 mutants carried a selective advantage over the antimicrobial-sensitive
      parent strain, indicating that FQ resistance in S. Typhi is not typically
      associated with fitness costs. Double-mutants exhibited higher than expected
      fitness as a result of synergistic epistasis, signifying that epistasis may be a
      critical factor in the evolution and molecular epidemiology of S. Typhi. Our
      findings have important implications for the management of drug-resistant S.
      Typhi, suggesting that FQ-resistant strains would be naturally maintained even if
      fluoroquinolone use were reduced. DOI: http://dx.doi.org/10.7554/eLife.01229.001.

PMID- 24327560
TI  - Hydrogen bonds as molecular timers for slow inactivation in voltage-gated
      potassium channels.
AB  - Voltage-gated potassium (Kv) channels enable potassium efflux and membrane
      repolarization in excitable tissues. Many Kv channels undergo a progressive loss
      of ion conductance in the presence of a prolonged voltage stimulus, termed slow
      inactivation, but the atomic determinants that regulate the kinetics of this
      process remain obscure. Using a combination of synthetic amino acid analogs and
      concatenated channel subunits we establish two H-bonds near the extracellular
      surface of the channel that endow Kv channels with a mechanism to time the entry
      into slow inactivation: an intra-subunit H-bond between Asp447 and Trp434 and an
      inter-subunit H-bond connecting Tyr445 to Thr439. Breaking of either interaction
      triggers slow inactivation by means of a local disruption in the selectivity
      filter, while severing the Tyr445-Thr439 H-bond is likely to communicate this
      conformational change to the adjacent subunit(s). DOI:
      http://dx.doi.org/10.7554/eLife.01289.001. 

PMID- 24327561
TI  - Development of schemas revealed by prior experience and NMDA receptor knock-out.
AB  - Prior experience accelerates acquisition of novel, related information through
      processes like assimilation into mental schemas, but the underlying neuronal
      mechanisms are poorly understood. We investigated the roles that prior experience
      and hippocampal CA3 N-Methyl-D-aspartate receptor (NMDAR)-dependent synaptic
      plasticity play in CA1 place cell sequence encoding and learning during novel
      spatial experiences. We found that specific representations of de novo
      experiences on linear environments were formed on a framework of pre configured
      network activity expressed in the preceding sleep and were rapidly, flexibly
      adjusted via NMDAR-dependent activity. This prior experience accelerated encoding
      of subsequent experiences on contiguous or isolated novel tracks, significantly
      decreasing their NMDAR-dependence. Similarly, de novo learning of an alternation
      task was facilitated by CA3 NMDARs; this experience accelerated subsequent
      learning of related tasks, independent of CA3 NMDARs, consistent with a schema
      based learning. These results reveal the existence of distinct neuronal encoding
      schemes which could explain why hippocampal dysfunction results in anterograde
      amnesia while sparing recollection of old, schema-based memories. DOI:
      http://dx.doi.org/10.7554/eLife.01326.001. 

PMID- 24327563
TI  - Fitness gains hamper efforts to tackle drug resistance.
AB  - It has long been assumed that resistance to antibiotics reduces the fitness of
      disease-causing bacteria, but experiments on Salmonella Typhi, the bacteria that
      causes Typhoid fever, are now challenging this view. 

PMID- 24327562
TI  - A Gata3-Mafb transcriptional network directs post-synaptic differentiation in
      synapses specialized for hearing.
AB  - Information flow through neural circuits is determined by the nature of the
      synapses linking the subtypes of neurons. How neurons acquire features distinct
      to each synapse remains unknown. We show that the transcription factor Mafb
      drives the formation of auditory ribbon synapses, which are specialized for rapid
      transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs
      to drive differentiation of the large postsynaptic density (PSD) characteristic
      of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs,
      leading to reduced synapse number and impaired auditory responses. Conversely,
      increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for
      executing one branch of the SGN differentiation program orchestrated by the Gata3
      transcriptional network. Remarkably, restoration of Mafb rescues the synapse
      defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type
      specific features of auditory synaptogenesis that offers a new entry point for
      treating hearing loss. DOI: http://dx.doi.org/10.7554/eLife.01341.001. 

PMID- 24327564
TI  - Quantitative determination of alkannins and shikonins in endemic Mediterranean
      Alkanna species.
AB  - The optical antipodes alkannin/shikonin (A/S) and their esters are potent
      pharmaceutical substances found in the roots of 150 Boraginaceous species. This
      study estimated and compared total and free A/S content and A/S enantiomeric
      ratio in roots of 11 Alkanna species (A. corcyrensis, A. tinctoria, A. pindicola,
      A. orientalis, A. methanaea, A. calliensis, A. graeca, A. primuliflora, A.
      stribrnyi, A. sieberi and A. noneiformis) growing wild in various Greek regions,
      to compare with cultivated species. It also re-characterized the chirality of A/S
      commercial samples, since most of them were misnamed by the providers. Several
      Alkanna species were collected (groups 1 and 3) and botanically identified,
      whereas some Alkanna species were cultivated from collected seeds (group 2). Free
      A/S and derivatives were extracted from the dried roots of Alkanna species and
      analyzed by high performance liquid chromatography-diode array detection (HPLC
      DAD). For total A/S content the hexane extracts of Alkanna roots were hydrolyzed
      and analyzed by HPLC-DAD. Chirality determination and A/S enantiomeric ratio
      estimation was performed for several commercial samples by polarimetry,chiral LC
      DAD and circular dichroism studies. Quantitative analysis revealed that A/S
      content varied from one region to another even within the same species. Most of
      the cultivated samples contained greater amounts of free and total A/S compared
      with the wild ones, wheras no difference was observed in A/S enantiomeric ratio.
      All the Alkanna samples tested contain mainly alkannin derivatives. Some of the
      examined Alkanna species of the Greek flora that are endemic to the Mediterranean
      area could serve as alternative sources for medicinally valuable A/S derivatives.
      Most of the commercial A/S samples tested were misnamed in terms of chirality and
      re-characterized.

PMID- 24327565
TI  - Fistula-first and catheter-last: fading certainties and growing doubts.

PMID- 24327567
TI  - NMR study of O and N, O-substituted 8-quinolinol derivatives.
AB  - The (1)H and (13)C NMR spectral study of several biologically active derivatives
      of 8-quinolinol have been made through extensive NMR studies including
      homodecoupling and 2D-NMR experiments such as COSY-45 degrees , NOESY, and
      HeteroCOSY. Electron donating resonance and electron withdrawing inductive effect
      of several groups showed marked changes in chemical shifts of nuclei at the
      seventh positions of O-substituted quinolinols (2-15). Although in N-alkyl, 8
      alkoxyquinolinium halides (16-21), ring A rightly showed low frequency chemical
      shift values.

PMID- 24327566
TI  - Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race.
AB  - BACKGROUND: African Americans have more severe hypertensive nephrosclerosis than
      white Americans, possibly at similar levels of blood pressure. Glomerular volume
      is increased in African Americans relative to whites, but it is uncertain how
      this relates to nephrosclerosis and whether it contributes to or compensates for
      glomerulosclerosis. METHODS: Stereological disector/fractionator estimates of
      glomerular number (N(glom)) and average glomerular volume (V(glom)) were obtained
      on autopsy kidneys of 171 African Americans and 131 whites. Eighty-eight African
      Americans and 49 whites were identified as hypertensive. Nephrosclerosis was
      measured morphometrically as the percentage of glomerulosclerosis, proportion of
      cortical fibrosis and interlobular artery intimal thickness, and analyzed with
      V(glom) by age, race, gender, body mass index (BMI) and blood pressure. RESULTS:
      African Americans were more frequently hypertensive (58.5%) than whites (35.8%)
      and when hypertensive had higher levels of blood pressure (P = 0.02). N(glom) was
      significantly lower in hypertensive compared with non-hypertensive subjects among
      white women (P = 0.02) but not white males (P = 0.34) or African American females
      (P = 0.10) or males (P = 0.41). For each race and gender, glomerulosclerosis,
      cortical fibrosis and arterial intimal thickening were statistically correlated
      with age (P < 0.001) and hypertension (P < 0.001) and increased V(glom) with
      hypertension (P < 0.001) and BMI (P < 0.001). In multivariate analysis, African
      American race was associated with increased V(glom) (P = 0.01) and arterial
      intimal thickening (P < 0.01), while interactions between race and blood pressure
      indicated that the severity of nephrosclerosis including increased V(glom) was
      linked most directly to hypertension without significant contributions from race.
      The hypertension-associated enlargement of V(glom) was present with mild degrees
      of glomerulosclerosis and changed little as the severity of glomerulosclerosis
      increased. CONCLUSIONS: Glomerular hypertrophy was identified as an integral
      feature of hypertensive nephropathy and appeared to precede rather than
      compensate for glomerulosclerosis. An effect of race on V(glom) and arterial
      intimal thickening seemed to be related to the more frequent and more severe
      hypertension among African Americans.

PMID- 24327568
TI  - A 4-MicroRNA signature can discriminate primary lymphomas from anaplastic
      carcinomas in thyroid cytology smears.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) and primary thyroid lymphoma (PTL)
      are uncommon tumors of the thyroid gland with several overlapping clinical and
      pathologic features that may render their differentiation difficult in fine
      needle aspiration (FNA) cytology. MicroRNA (miRNA) signatures have been recently
      reported as useful diagnostic tools applied to cytology specimens. METHODS:
      Smears of 23 ATCs, 14 PTLs, and 20 non-neoplastic materials with multinodular
      goiter (MNG) were retrieved and classified based on their cytologic features and
      flow cytometric profiles. The ATC-related expression of hsa-miR-26a, hsa-miR
      146b, hsa-miR-221, and hsa-miR-222 was quantified using quantitative reverse
      transcriptase-polymerase chain reaction analysis. RESULTS: All miRNAs were
      remarkably up-regulated in ATC samples compared with PTL samples (P < .01).
      Moreover, expression levels of hsa-miR-146b, hsa-miR-221, and hsa-miR-222 were
      significantly higher in ATCs than in MNG samples (P < .01). Significant down
      regulation of hsa-miR-26a was observed in PTLs compared with MNG samples, whereas
      hsa-miR-146b was overexpressed. Receiver operating characteristic analysis was
      used to determine the optimal cutoff for distinguishing ATC from PTL. The
      estimated receiver operating characteristic thresholds displayed a sensitivity
      level greater than 0.80 in achieving a diagnosis of PTL, allowing the correct
      identification of 13 of 14 PTL samples (93%). CONCLUSIONS: Histotype-specific
      miRNA signatures can provide new insight into the molecular mechanisms of thyroid
      carcinogenesis. The tested 4-miRNA signature is a promising diagnostic tool for
      differentiating ATC from PTL and non-neoplastic MNG, even in the presence of
      scant material obtained from minimally invasive procedures.

PMID- 24327569
TI  - Simultaneous immobilization of heparin and gentamicin on polypropylene textiles:
      a dual therapeutic activity.
AB  - The aim of this work was to prepare a nonwoven polypropylene (PP) textile
      functionalized with bioactive molecules in order to improve simultaneously
      anticoagulation and antibacterial properties. The immobilization of either
      heparin (anticoagulation agent) or gentamicin (aminoglycoside class antibiotic)
      alone has already been proven to be effective on PP nonwoven textiles. In this
      work, we managed to go further, by immobilizing both heparin and gentamicin at
      the same time on one unique textile. A successive immersion in different heparin
      and gentamicin bathes successfully led to a dual drug coated textile, as
      confirmed by several characterization techniques (Fourier transform infrared
      attenuated total reflectance, X-ray photoelectron spectroscopy, and scanning
      electron microscopy). The immobilization times were varied in order to determine
      the best compromise between cytocompatibility, anticoagulant effect, and
      antimicrobial activity. Short immersion times in gentamicin solutions confer very
      good antimicrobial activity to the textile and avoid cytotoxicity, whereas long
      immersion times in heparin solution were necessary to observe a significant
      anticoagulant effect.

PMID- 24327570
TI  - Manganese oxide/graphene aerogel composites as an outstanding supercapacitor
      electrode material.
AB  - Graphene aerogels (GA), prepared with an organic sol-gel process, possessing a
      high specific surface area of 793 m(2)  g(-1) , a high pore volume of 3 cm(3)  g(
      1) , and a large average pore size of 17 nm, were applied as a support for
      manganese oxide for supercapacitor applications. The manganese oxide was
      electrochemically deposited into the highly porous GA to form MnO2 /GA
      composites. The composites, at a high manganese oxide loading of 61 wt. %,
      exhibited a high specific capacitance of 410 F g(-1) at 2 mV s(-1) . More
      importantly, the high rate specific capacitances measured at 1000 mV s(-1) for
      these composites were two-fold higher than those obtained with samples prepared
      in the absence of the GA support. The specific capacitance retention ratio, based
      on the specific capacitance obtained at 25 mV s(-1) , was maintained high, at 85
      %, even at the high scan rate of 1000 mV s(-1) , in contrast with the
      significantly lower value of 67 % for the plain manganese oxide sample. For the
      cycling stability, the specific capacitance of the composite electrode decayed by
      only 5 % after 50,000 cycles at 1000 mV s(-1) . The success of this MnO2 /GA
      composite may be attributed to the structural advantages of high specific surface
      areas, high pore volumes, large pore sizes, and three-dimensionally well
      connected network of the GA support. These structural advantages made possible
      the high mass loading of the active material, manganese oxide, large amounts of
      electroactive surfaces for the superficial redox events, fast mass-transfer
      within the porous structure, and well-connected conductive paths for the involved
      charge transport.

PMID- 24327571
TI  - A comparison of outpatient healthcare expenditures between public and private
      medical institutions in urban China: an instrumental variable approach.
AB  - The growth of healthcare expenditure provokes constant comments and discussions,
      as countries battle the issues on cost containment and cost effectiveness. Prior
      to 1978, medical institutions in China were either state-owned or were collective
      public hospitals. Since 1978, China has been trying to rebuild its healthcare
      system, which was destroyed during the 'cultural revolution', allowing private
      medical institutions to deliver healthcare services. As a result, private medical
      institutions have grown from 0% to 28.57% between 1978 and 2010. In this context,
      we compare outpatient healthcare expenditures between public and private medical
      institutions. The central problem of this comparison is that the choice of
      medical institution is endogenous. So we apply an instrumental variable (IV)
      framework utilizing geographic information (whether the closest medical
      institution is private) as the instrument while controlling for severity of
      health and other relevant confounding factors. Using China's Urban Resident Basic
      Medical Insurance Survey 2008-2010, we found that there is no difference in
      expenditure between public and private medical institutions when IV framework is
      used. Our econometric tests suggest that our IV model is specified appropriately.
      However, the ordinary least square model, which is inconsistent in the presence
      of endogenous regressor(s), reveals that public medical institutions are more
      expensive.

PMID- 24327572
TI  - Does interleukin-17 play the villain in nonalcoholic steatohepatitis?

PMID- 24327574
TI  - A simple technique to control placement of Dumon stent in subglottic tracheal
      stenosis.
AB  - Airway stenting is the chosen treatment for patients affected by subglottic
      tracheal stenosis and unfit for surgery. Among the different types of prostheses,
      the Dumon stent is a valid option especially in patients without tracheotomy.
      Insertion is usually achieved by pushing the stent off from a loader using a
      prosthesis pusher. If the stent is expelled below the stenosis, rigid forceps
      grasping the proximal end of the stent retract it above the stenosis. However, in
      difficult cases such as rigid stenosis with a luminal diameter smaller than the
      profile of the stent, such a manoeuvre may be difficult in non-expert hands.
      Thus, we proposed a simple and safe technique to facilitate the placement of a
      Dumon stent. We passed a long thread from outside to the inside of the stent.
      After the dilatation of the stenosis, the stent was pushed and, if needed, easily
      retracted with the thread into the proper position to ensure airway patency and
      to avoid migration. In addition, our procedure could be useful also to rapidly
      remove the stent if its size turned out to be inaccurate for the stenosis. With
      such a simple method we successfully treated 7 consecutive patients affected by
      complex subglottic stenosis and unfit for surgery. 

PMID- 24327575
TI  - Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) contributes to a
      triple-negative test in preoperative screening of pancreatic cysts.
AB  - BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of
      pancreatic cysts obtains cyst fluid for cytologic and biochemical analysis, which
      may determine whether the cyst is mucinous and malignant, contributing to patient
      management. Despite this added value, EUS-FNA remains controversial in the
      preoperative assessment of pancreatic cysts. The objective of this study was to
      assess the utility of EUS-FNA in a cohort of small pancreatic cysts that were
      benign on imaging studies. METHODS: All pancreatic cysts that underwent initial
      EUS-FNA in 2006 and 2007 were retrospectively analyzed. Ninety-two patients with
      pancreatic cysts met the inclusion criteria. Patients who had high-risk or
      worrisome features on imaging studies were excluded. Cytology, histology, and
      cyst fluid analysis data were collected. The main outcome measurements were
      radiologic and clinical follow-up as well as cytopathologic and histologic
      results. RESULTS: EUS-FNA supported a diagnosis of a mucinous cyst in 38 of 92
      patients (41%) by carcinoembryonic antigen (CEA) measurement and/or cytology.
      Cytology demonstrated an absence of high-grade atypia (HGA) in 89 of 92 patients
      (97%). The mean follow-up was 4.4 years (range, 0-7.7 years), during which 6
      cysts were surgically resected and 16 cysts were resampled by at least 1
      subsequent EUS-FNA. The overall negative predictive value of cytologic
      examination for HGA was 99%. CONCLUSIONS: EUS-FNA is a screening test that
      contributes to a triple-negative test for pancreatic cysts--no high-risk
      stigmata, no worrisome features, and no HGA on cytology--providing a negative
      predictive value of 99% for conservative management.

PMID- 24327573
TI  - Effects of hepatocyte growth factor in myocarditis rats induced by immunization
      with porcine cardiac myosin.
AB  - OBJECTIVES: Myocarditis is considered one of the major causes of dilated
      cardiomyopathy. Hepatocyte growth factor (HGF) has pleiotropic activities that
      promote tissue regeneration and facilitate functional improvement of injured
      tissue. We investigated whether the epicardial sustained-release of HGF, using
      gelatin hydrogel sheets, improves cardiac function in a chronic myocarditis rat
      model. METHODS: Six weeks after Lewis rats were immunized with porcine cardiac
      myosin to establish autoimmune myocarditis, HGF- or normal saline (NS)
      incorporated gelatin hydrogel sheets were applied to the epicardium (G-HGF and G
      NS, respectively). At either 2 or 4 weeks after treatment, these were compared
      with the Control myocarditis group. Cardiac function was evaluated by
      echocardiography and cardiac catheterization. Development of fibrosis was
      determined by histological study and expression of transforming growth factor
      beta1 (TGF-beta1). Bax and Bcl-2 levels were measured to evaluate apoptotic
      activity. RESULTS: At both points, fractional shortening and end-systolic
      elastance were higher in the G-HGF group than in the Control and G-NS groups (P <
      0.01). Fractional shortening at 2 weeks of each group were as follows: 31.0 +/-
      0.9%, 24.8 +/- 2.7% and 48.6 +/- 2.6% (Control, G-NS and G-HGF, respectively).
      The ratio of the fibrotic area of the myocardium was lower in the G-HGF group
      than in the Control and G-NS groups at 2 weeks (G-HGF, 8.8 +/- 0.9%; Control,
      17.5 +/- 0.2%; G-NS, 15.6 +/- 0.7%; P < 0.01). The ratio at 4 weeks was lower in
      the G-HGF group than in the G-NS group (10.9 +/- 1.4% vs 18.5 +/- 1.3%; P <
      0.01). The mRNA expression of TGF-beta1 in the G-HGF group was lower than in the
      Control group at 2 weeks (0.6 +/- 0.1 vs 1.1 +/- 0.2) and lower than that in the
      G-NS group at 4 weeks (0.7 +/- 0.1 vs 1.3 +/- 0.2). The Bax-to-Bcl-2 ratios at
      both points were lower in the G-HGF group than in the Control group. CONCLUSIONS:
      Sustained-released HGF markedly improves cardiac function in chronic myocarditis
      rats. The antifibrotic and antiapoptotic actions of HGF may contribute to the
      improvement. HGF-incorporated gelatin hydrogel sheet can be a new therapeutic
      modality for myocarditis.

PMID- 24327576
TI  - Can anatomists teach living anatomy using ultrasound as a teaching tool?
AB  - The utilization of bedside ultrasound by an increasing number of medical
      specialties has created the need for more ultrasound exposure and teaching in
      medical school. Although there is a widespread support for more vertical
      integration of ultrasound teaching throughout the undergraduate curriculum,
      little is known about whether the quality of ultrasound teaching differs if
      performed by anatomists or clinicians. The purpose of this study is to compare
      medical students' evaluation of ultrasound anatomy teaching by clinicians and
      anatomists. Hands-on interactive ultrasound sessions were scheduled as part of
      the gross anatomy course following principles of adult learning and instructional
      design. Seven teachers (three anatomists and four clinicians) taught in each
      session. Before each session, anatomists were trained in ultrasound by
      clinicians. Students were divided into groups, rotated teachers between sessions,
      and completed evaluations. Results indicated students perceived the two groups as
      comparable for all factors except for knowledge organization and the helpfulness
      of ultrasound for understanding anatomy (P < 0.001). However, results from
      unpaired samples t-tests demonstrated a nonstatistically significant difference
      between the groups within each session for both questions. Moreover, students'
      test performance for both groups was similar. This study demonstrated that
      anatomists can teach living anatomy using ultrasound with minimal training as
      well as clinicians, and encourage the teaching of living anatomy by anatomists in
      human anatomy courses using ultrasound. Repeating this study at a multicenter
      level is currently being considered to further validate our conclusion.

PMID- 24327577
TI  - Improvement in institutional protocols leads to decreased mortality in patients
      with haemodynamically unstable pelvic fractures.
AB  - BACKGROUND: The mortality rate in patients with haemodynamically unstable pelvic
      fractures is as high as 40-60%. In recent years, angioembolisation and pelvic
      packing have been introduced as part of a multimodality treatment for these
      patients. Protocol-driven management has been shown to improve outcomes. PATIENTS
      AND METHODS: This is a Level III retrospective cohort study of patients suffering
      from unstable pelvic fractures from 1 January 1996 to 30 September 2011. The aim
      of the study was to review our results, particularly in terms of mortality
      through the evolution of three phases of treatment protocols: preangiography,
      angiography and pelvic packing. RESULTS: The overall 30-day mortality rate for
      all patients was 47.2%, with a rate of 63.5% in the preangiography phase, 42.1%
      in the angiography phase and 30.6% in the pelvic packing phase. Multivariate
      logistic regression analysis identified the use of retroperitoneal packing as a
      significant independent predictive factor for 24 h mortality. CONCLUSIONS: Our
      results showed an improvement in patient survival with sequential protocols over
      the study period, during which we incorporated a multidisciplinary approach to
      managing these complicated pelvic fractures. The results strongly suggest that
      retroperitoneal packing should be highly recommended for bleeding subsequent to
      pelvic fracture, in addition to other modalities of treatment.

PMID- 24327578
TI  - CanFOAMed: Canadians can do FOAM too.

PMID- 24327579
TI  - Proper compression landmark and depth for cardiopulmonary resuscitation in
      patients with pectus excavatum: a study using CT.
AB  - OBJECTIVE: To determine by chest CT the proper compression landmark and depth for
      cardiopulmonary resuscitation in patients with pectus excavatum (PE). METHODS:
      The chest CT of 22 patients with PE (mean age=27 years; range 16-53 years, 10
      male) from March 2002 to September 2011 were retrospectively evaluated as
      follows: length of sternum, external thickness/internal thickness (ET/IT) of the
      chest and the intrathoracic structures in the level of lower half (LH) of the
      sternum. In addition, Haller index (HI) and the degree of leftward displacement
      of the heart were measured. Finally, variables were also measured in an age/sex
      matched control group (n=22) with no evidence of any chest wall deformity.
      RESULTS: The sternal length was not different and LH of the sternum was adequate
      to compress left ventricle (LV) in both groups. Patients had a significant higher
      HI and showed a greater leftward displacement of LV centre with a mean difference
      of 11 mm. PE patients showed a lesser ET/IT with a mean difference of
      approximately 20 mm than controls (mean ET/IT=174+/-18/70+/-10 mm vs 199+/
      23/93+/-15 mm, p<0.001). CONCLUSIONS: The LH of the sternum is an appropriate
      chest compression landmark in PE patients to compress LV, although the centre of
      LV shows slightly leftward displacement. Since PE patients have sunken chest, a 3
      4 cm may be the proper compression depth in the patients when considering the
      current compression guideline in normal subjects is 5-6 cm.

PMID- 24327580
TI  - Patterns of vulnerability to non-fatal injuries in Sudan: initial evidence from a
      national cross-sectional survey.
AB  - BACKGROUND: Successful injury prevention requires identification and targeting of
      particularly vulnerable groups. Little is known about injury vulnerability
      patterns in Sudan. This paper aimed to fill this gap using survey data. METHODS:
      Data from the Sudan Household Health Survey were used. This was a national cross
      sectional interview survey of 83,510 individuals selected by multistage cluster
      random sampling. Multivariable Poisson regression was used to investigate the
      association of cause-specific injury that received care by traditional healers,
      outpatient care and inpatient care, and those that received only inpatient care,
      with age, gender, area of residence (urban or rural), socioeconomic status and
      education. Relevant interactions were tested. RESULTS: Independent of other
      sociodemographic variables, men were at higher risk of road traffic injury
      (prevalence ratio (PR): 3.3 95% CI 2.4 to 4.7), falls (PR: 1.5, 95% CI 1.3 to
      1.9), assault (PR: 3.0 95% CI 1.8-5) and mechanical injury (PR: 2.0 95% CI 1.2 to
      3.1) that received any form of healthcare. Those aged 65 years and over also had
      the highest risk of those injury causes, while children under 5 years were the
      most likely to suffer burn injuries. Socioeconomic status was associated with
      assault (PR for the richest group 0.4 95% CI 0.2 to 0.8). Vulnerability patterns
      for injury that received inpatient care were fairly similar for some causes.
      CONCLUSIONS: In Sudan, existing disease prevention and health promotion
      programmes should expand to target men, children under 5 years, elderly people
      and those of low socioeconomic status with injury prevention interventions.
      Further research is needed to investigate the context-specific proximal risk
      factors that shape the various vulnerability patterns observed.

PMID- 24327581
TI  - Association of matrix metalloproteinase 2 plasma level with response and survival
      in patients treated with bevacizumab for recurrent high-grade glioma.
AB  - BACKGROUND: A predictive marker of bevacizumab activity is an unmet medical need.
      We evaluated the predictive value of selected circulating prebiomarkers involved
      in neoangiogenesis and invasion on patient outcome in recurrent high-grade glioma
      treated with bevacizumab. METHODS: Analyzed in plasma were a set of 11
      prebiomakers of interest (vascular endothelial growth factor receptor [VEGF];
      VEGF receptor 2; basic fibroblast growth factor; stromal cell derived factor 1;
      placenta growth factor; urokinase-type plasminogen activator; plasminogen
      activator inhibitor 1; matrix metalloproteinases 2, 7, and 9; and
      adrenomedulline), using ELISA, at baseline and 2 weeks after bevacizumab
      initiation in a prospective cohort of 26 patients (Cohort 1). Correlations were
      validated in a separate retrospective cohort (Cohort 2; n = 50) and tested in
      cohort patients treated with cytotoxic agents without bevacizumab (Cohort 3; n =
      34). Dosages were correlated to objective response, progression-free survival
      (PFS), and overall survival (OS). RESULTS: In Cohort 1, high MMP2 baseline level
      was associated with a probability of objective response of 83.3% versus 15.4% for
      low MMP2 level (P = .001). In multivariate analysis, baseline level of MMP2
      correlated with PFS (hazard ratio, 3.92; 95% confidence interval [CI]:1.46-10.52;
      P = .007) and OS (hazard ratio, 4.62; 95% CI: 1.58-13.53; P = .005), as decrease
      of VEGF (P = .038 for PFS and P = .013 for OS) and MMP9 (P = .016 for PFS and P =
      .025 for OS). In Cohort 2, MMP2, but not MMP9, confirmed its predictive
      significance. In Cohort 3, no association was found between MMP2, MMP9, and
      outcome. CONCLUSION: In patients with recurrent high-grade glioma treated with
      bevacizumab, but not with cytotoxic agent, high MMP2 plasma levels are associated
      with prolonged tumor control and survival. MMP2 should be tested in randomized
      clinical trials that evaluate bevacizumab efficacy, and its biological role
      reassessed.

PMID- 24327582
TI  - A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of
      glioblastoma-initiating cells.
AB  - BACKGROUND: There are emerging reports that the family of a disintegrin and
      metalloproteinases (ADAM) are involved in the maintenance of the malignant
      phenotype of glioblastomas. Notably, ADAM proteases 10 and 17 might impair the
      immune recognition of glioma cells via the activating immunoreceptor NKG2D by
      cleavage of its ligands from the cell surface. Glioblastoma-initiating cells
      (GIC) with stem cell properties have been identified as an attractive target for
      immunotherapy. However, GIC immunogenicity seems to be low. METHODS AND RESULTS:
      Here,we show that ADAM10 and ADAM17 are expressed on the cell surface of GIC and
      contribute to an immunosuppressive phenotype by cleavage of ULBP2. The cell
      surface expression of ULBP2 is enhanced upon blocking ADAM10 and ADAM17, and
      treatment with ADAM10 and ADAM17specific inhibitors leads to enhanced
      immunerecognition of GIC by natural killer cells. CONCLUSIONS: Therefore, ADAM10
      and ADAM17 constitute suitable targets to boost an immune response against GIC.

PMID- 24327583
TI  - Induced interleukin-33 expression enhances the tumorigenic activity of rat glioma
      cells.
AB  - BACKGROUND: Glioma development is a multistep process associated with progressive
      genetic alterations but also regulated by cellular and noncellular components in
      a tumor-associated niche. METHODS: Using 2 rat C6 glioma cell clones with
      different tumorigenesis, named C6-1 and C6-2, this study characterized genes
      associated with enhanced tumorigenic features of glioma cells by comparative cDNA
      microarray analysis combined with Q-PCR. Neurospehere formation and clonogenicity
      were examined to determine the growth of tumorigenic C6 glioma cells. The
      lentivirus-mediated gene knockdown approach was conducted to determine the role
      of interleukin-33 (IL-33) in glioma cell proliferation and migration. Transwell
      cell invasion assay was used to examine microglia migration induced by
      tumorigenic C6 cells. RESULTS: The functional analysis of gene ontology (GO)
      biological processes shows that the upregulated genes found in tumorigenic C6 (C6
      1) cells are closely related to cell proliferation. Tumorigenic C6 cells
      expressed cytokines and chemokines abundantly. Among these genes, IL-33 was
      profoundly induced in tumorigenic C6 cells with the expression of IL-33 receptor
      ST2. Furthermore, the growth rate and colony formation of tumorigenic C6 cells
      were attenuated by the inhibition of IL-33 and ST2 gene expression. Moreover, IL
      33 was involved in tumorigenic glioma cell migration and regulation of the
      expression of several glioma-associated growth factors and chemokines in
      tumorigenic C6 cells. CONCLUSION: Accordingly, we concluded that glioma cells
      with abundant production of IL-33 grow rapidly; moreover, the interactions of
      multiple cytokines/chemokines induced by glioma cells may develop a
      microenvironment that facilitates microglia/macrophage infiltration and fosters
      glioma growth in the brain.

PMID- 24327585
TI  - Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of
      treatment margins and treatment technique.
AB  - BACKGROUND: We investigated how varying the treatment margin and applying
      hippocampal sparing and proton therapy impact the risk of neurocognitive
      impairment in pediatric medulloblastoma patients compared with current standard
      3D conformal radiotherapy. METHODS: We included 17 pediatric medulloblastoma
      patients to represent the variability in tumor location relative to the
      hippocampal region. Treatment plans were generated using 3D conformal
      radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot
      scanned proton therapy, using 3 different treatment margins for the conformal
      tumor boost. Neurocognitive impairment risk was estimated based on dose-response
      models from pediatric CNS malignancy survivors and compared among different
      margins and treatment techniques. RESULTS: Mean hippocampal dose and
      corresponding risk of cognitive impairment were decreased with decreasing
      treatment margins (P < .05). The largest risk reduction, however, was seen when
      applying hippocampal sparing proton therapy-the estimated risk of impaired task
      efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50%
      (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and
      proton therapy, respectively, for the smallest boost margin and 98% (78%-100%),
      90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the
      distance between the closest point of the planning target volume and the center
      of the hippocampus can be used to predict mean hippocampal dose for a given
      treatment technique. CONCLUSIONS: We estimate a considerable clinical benefit of
      hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff
      between margin size and risk of neurocognitive impairment quantified here should
      be considered.

PMID- 24327584
TI  - Investigation of the diffusion abnormality index as a new imaging biomarker for
      early assessment of brain tumor response to radiation therapy.
AB  - BACKGROUND: Diffusion MRI, although having the potential to be a biomarker for
      early assessment of tumor response to therapy, could be confounded by edema and
      necrosis in or near the brain tumors. This study aimed to develop and investigate
      the ability of the diffusion abnormality index (DAI) to be a new imaging
      biomarker for early assessment of brain metastasis response to radiation therapy
      (RT). METHODS: Patients with either radiosensitive or radioresistant brain
      metastases that were treated by whole brain RT alone or combined with bortezomib
      as a radiation sensitizer had diffusion-weighted (DW) MRI pre-RT and 2 weeks (2W)
      after starting RT. A patient-specific diffusion abnormality probability function
      (DAProF) was created to account for abnormal low and high apparent diffusion
      coefficients differently, reflecting respective high cellularity and
      edema/necrosis. The DAI of a lesion was then calculated by the integral of DAProF
      weighted tumor apparent diffusion coefficient histogram. The changes in DAI from
      pre-RT to 2W were evaluated for differentiating the responsive, stable, and
      progressive tumors and compared with the changes in gross tumor volume and
      conventional diffusion metrics during the same time interval. RESULTS: In lesions
      treated with whole brain RT, the DAI performed the best among all metrics in
      predicting the posttreatment response of brain metastases to RT. In lesions
      treated with whole brain RT + bortezomib, although DAI was the best predictor,
      the performance of all metrics worsened compared with the first group.
      CONCLUSIONS: The ability of DAI for early assessment of brain metastasis response
      to RT depends upon treatment regimes.

PMID- 24327586
TI  - Comparison of colorectal cancer screening in veterans based on the location of
      primary care clinic.
AB  - OBJECTIVES: To compare colorectal cancer screening rates in veterans receiving
      primary care (PC) in Veterans Administration (VA) community-based outpatient
      clinics (CBOCs) and VA medical centers (VAMCs). METHODS: The VA Outpatient Care
      Files were used to identify 2 837 770 patients >= 50 years with >= 2 PC visits in
      2010. Veterans undergoing screening/surveillance colonoscopy, sigmoidoscopy,
      fecal-occult-blood testing (FOBT), and double-contrast barium enema (DCBE) were
      identified from ICD-9-CM/CPT codes. Patients were categorized as VAMC (n = 1 403
      273; 49.5%) or CBOC (1 434 497; 50.5%) based on where majority of PC encounters
      occurred and as high risk (n = 284 090) or average risk (n = 2 553 680) based on
      colorectal cancer risk factors and validated ICD-9-CM-based algorithms. RESULTS:
      CBOC patients were older than VAMC (mean ages 69.3 vs 67.4 years; P < .001), more
      likely (P < .001) to be male (96.5% vs 95.1%), and white (67.8% vs 64.2%), but
      less likely to be high-risk (9.4% vs 10.5%; P < .001). Rates of colonoscopy,
      sigmoidoscopy, and DCBE were all lower in CBOC (P < .001). Among high-risk
      veterans, rates in CBOC and VAMC, respectively, were 27.4% versus 36.8% for
      colonoscopy, 1.3% versus 0.8% for sigmoidoscopy, and 0.8% versus 0.5% for DCBE.
      Among average-risk veterans, these rates were 1.3% versus 1.9%, 0.2% versus 0.1%,
      and 0.2% versus 0.1%, respectively. The differences remained after adjusting for
      age/comorbidity. The adjusted odds of colonoscopy for CBOC were 0.73 (95%
      confidence interval = 0.64-0.82) for average risk and 0.76 (95% confidence
      interval = 0.67-0.87) for high risk. In contrast, the use of FOBT was relatively
      similar in CBOCs and VAMCs among both high risk (11.1% vs 11.2%) and average risk
      (14.3% vs 14.1%). Screening rates were similar between those younger than 65
      years and older than 65 years. CONCLUSIONS: Veterans receiving PC in CBOCs are
      less likely to receive screening colonoscopy, sigmoidoscopy, and DCBE than VAMC
      according to VA records. The lower use in CBOC was not offset by higher use of
      FOBT, including the degree to which CBOC patients may be more reliant to use non
      VA services. The clinical appropriateness of these differences merits further
      examination.

PMID- 24327587
TI  - Temporal trends in the diagnosis and management of childhood obesity/overweight
      in primary care.
AB  - OBJECTIVE: To determine the temporal trends in diagnosis and management of
      pediatric overweight/obesity by primary care providers at a single medical
      center. PATIENTS: Children 2 to 18 years old undergoing a general medical
      examination during 3 calendar years (2003, 2006, and 2009). The number of visits
      for general medical examination were 6390 in 2003, 6646 in 2006, and 7408 in
      2009. METHODS: We performed a retrospective review of the electronic medical
      records for weight related diagnostic and/or management terms and laboratory
      screening in children with body mass index at or greater than the 85th percentile
      (n = 1630 in 2003, 1495 in 2006, and 1730 in 2009). RESULTS: There was a
      significant increase in the diagnosis of obesity among obese children seen in
      2009 (53.3%) compared with 2006 (36%, P < .001) and 2003 (24.3%, P < .001).
      Weight-related counseling was documented in a higher proportion of obese children
      in 2009 (49.4%) compared with 2006 (34.8%) and 2003 (26.6%). There was a
      significant increase in counseling regarding screen time in 2009 compared with
      2006. A significant increase in screening for nonalcoholic fatty liver disease
      was also noted (30.5% in 2009 vs 21.9% in 2006, P = .018). CONCLUSIONS: There has
      been steady improvement in the rates of obesity diagnosis and obesity-related
      counseling by primary care providers. However, continued efforts to increase
      awareness of these issues are needed as nearly half of obese children remained
      undiagnosed and recommended laboratory screening for obesity-related
      comorbidities was performed in only a third of obese children.

PMID- 24327588
TI  - Use of electronic clinical reminders to increase preventive screenings in a
      primary care setting: blueprint from a successful process in Kodiak, Alaska.
AB  - PURPOSE: The Kodiak Area Native Association (KANA) provides primary health care
      in Kodiak, Alaska and 6 outlying villages. KANA sought to actively improve key
      preventive screening rates for its patients. METHODS: KANA adopted an electronic
      health record in 2008 and deployed national clinical reminders from the Indian
      Health Service for 5 key preventive screenings: tobacco use, alcohol use,
      depression, intimate partner violence, and a comprehensive cardiovascular exam.
      Clinical reminders were deployed in a 5-step process: (a) establish clinical
      demand, (b) pilot test reminder, (c) expand reminder to all providers, (d)
      measure outcomes and share results, and (e) delegate clinical reminder follow-up
      (primarily to nurses). RESULTS: Data from 2007-2011 show screening rates for all
      5 measures improved considerably, to levels significantly above the national
      average for Indian Health Service facilities. CONCLUSIONS: Clinical reminders
      have been a key part of a multistep process to improve screening for depression,
      tobacco cessation, intimate partner violence, alcohol use, and cardiovascular
      disease. If deployed correctly, reminders are valuable tools in identifying
      patients who are overdue for preventive health screenings.

PMID- 24327589
TI  - Rewards and challenges of community health center practice.
AB  - BACKGROUND: More than 1100 community health centers (CHCs) in the United States
      provide primary care to 20 million underserved patients annually. CHCs have
      struggled to recruit and retain qualified physicians. OBJECTIVE: To understand
      physicians' work experiences in CHCs and identify major sources of satisfaction
      and dissatisfaction. METHODS: Using purposeful sampling, we conducted
      semistructured interviews with 12 family physicians practicing in CHCs. Interview
      questions assessed physicians' experiences in CHCs and sources of satisfaction
      and dissatisfaction. Interview notes were coded and analyzed by 2 investigators
      using a grounded theory approach to identify key themes. RESULTS: Though family
      physicians feel tremendous satisfaction from care of underserved patients, they
      are frustrated with the overwhelming workload they experience. Family physicians
      also report poor administrative management while working in CHCs. CONCLUSIONS:
      Implementation of the Affordable Care Act, which relies on expansion of CHC
      services, may be adversely affected by family physicians' frustrations with CHC
      practice. Further research to explore and potentially improve the CHC work
      environment may be needed.

PMID- 24327590
TI  - Impact of an outpatient pharmacist intervention on medication discrepancies and
      health care resource utilization in posthospitalization care transitions.
AB  - PURPOSE: Medication errors related to hospital discharge result in
      rehospitalization and emergency department (ED) visits, yet no systematic
      approach has been implemented nationally to decrease these medication errors.
      Pharmacist involvement during postdischarge transitions of care may be an
      important strategy to prevent and correct medication discrepancies and reduce
      costly rehospitalization and ED visits. METHODS: This prospective, randomized,
      open-label, pilot study evaluated the effect of a pharmacy clinic visit focused
      on medication reconciliation and patient education after hospital discharge on
      the incidence of rehospitalization and ED visits and the resolution of medication
      discrepancies. RESULTS: Of the 61 subjects included in the study, 33 (54%) had
      medication discrepancies identified at discharge. Fifty percent of medication
      discrepancies were resolved in subjects randomized to the pharmacist intervention
      arm compared with 9.5% in the usual care arm (P = .015). Patients randomized to
      the intervention arm had significantly lower rates of the primary composite
      outcome of 30-day rehospitalization and ED visits compared with the usual care
      arm (0% vs 40.5%, P < .001). CONCLUSION: A pharmacist-driven intervention focused
      on patient education and medication reconciliation after discharge improved
      medication use and reduced health care resource utilization in this pilot study.

PMID- 24327591
TI  - Multiple chronic conditions: diabetes associated with comorbidity and shared risk
      factors using CDC WEAT and SAS analytic tools.
AB  - BACKGROUND: Multiple chronic conditions (MCCs) are significant public health
      problems receiving much attention, and rightly so, because of the substantial
      morbidity, mortality, and cost burden. OBJECTIVES: To report the prevalence of
      selected frequent MCCs with shared risk factors that are leading causes of death;
      and to quantify the association between diabetes and its comorbidity and shared
      risk factors. METHODS: This is a cross-sectional study of 9172 participants in
      Pennsylvania's 2009 Behavioral Risk Factor Surveillance System (BRFSS). Centers
      for Disease Control and Prevention's Web Enabled Analysis Tool (WEAT) and SAS
      Proc Survey were used for all analyses, to account for BRFSS's multistage complex
      survey design and sample weights. RESULTS: SAS estimated prevalence among >=35
      year-olds were as follows: diabetes (11.9%), heart disease (9.5%), stroke (3.3%),
      diabetes and heart disease (2.9%), diabetes and stroke (1.0%), heart disease and
      stroke (1.1%), and diabetes, heart disease, and stroke (0.4%). Adults >=35 years
      old with the following characteristics were more likely to have diabetes when
      self-reporting: obese (adjusted odds ratio [ORAdj] = 4.63, 95% confidence
      interval [95% CI] = 3.41-6.30); low income (<$15 000 ORAdj = 2.85, 95% CI = 1.90
      4.27; $15 000-$24 999 ORAdj = 2.07, 95% CI = 1.50-2.86; $25 000-$34 999 ORAdj =
      2.06, 95% CI = 1.47-2.88; $35 000-$49 999 ORAdj = 1.51, 95% CI = 1.08-2.12);
      elderly >=65 years old (ORAdj = 2.84, 95% CI = 1.76-4.56); non-Hispanic black
      (ORAdj = 2.54, 95% CI = 1.08-6.00); overweight (ORAdj = 1.99, 95% CI = 1.47
      2.68); heart disease (ORAdj = 1.94, 95% CI = 1.47-2.56); 45 to 64 years old
      (ORAdj = 1.88 95%, CI = 1.21-2.93); hypertension (ORAdj = 1.78, 95% CI = 1.39
      2.29); stroke (ORAdj = 1.62, 95% CI = 1.05-2.50); high cholesterol (ORAdj = 1.49,
      95% CI = 1.18-1.88); physically inactive (ORAdj = 1.33 95% CI = 1.06-1.67); and
      men (ORAdj = 1.32, 95% CI = 1.04-1.67). CONCLUSION: Adults with comorbidity and
      risk factors were 1.3 to 4.6 times more likely to have diabetes, with obesity
      consistently the strongest risk factor. WEAT's limitations are the predefined
      categories, inability to restrict to specific age groups and to estimate the
      prevalence of >2 MCCs. WEAT has considerable potential to advance evidence-based
      primary care practice and community health programs, such as state-wide programs
      that target obesity and physical inactivity. The robust capability of SAS to
      calculate MCC prevalence and adjusted associations with risk factors provides the
      fundamentals for developing and evaluating primary care services and community
      health programs.

PMID- 24327592
TI  - Working conditions and parents' ability to care for children's preventive health
      needs.
AB  - OBJECTIVE: To determine whether workplace flexibility policies influence parents'
      ability to meet their children's preventive primary health care needs. PATIENTS
      AND METHODS: Study sample included 917 employed adults with at least 1 child
      younger than 18 years in their household from a nationally representative survey
      of US adults. Multivariate logistic regression analyses of factors influencing
      parental ability to meet their children's preventive primary health care needs
      were conducted. Analyses assessed the effect of having access to schedule
      flexibility, a supervisor who is accommodating about work adjustments when family
      issues arise, and the ability to make personal calls without consequences on the
      odds of a parents' being unable to meet their child's preventive health care
      needs. RESULTS: Being able to make a personal phone call at work was associated
      with a 56% (P < .05) reduction in the odds of being unable to meet children's
      preventive health needs. Working at a job that allowed for schedule adjustments
      was associated with more than 40% (P < .05) lower odds of being unable to meet
      preventive care needs. CONCLUSION: Feasible steps to increase flexibility at work
      could make a substantial difference in parents' ability to obtain preventive care
      for their children.

PMID- 24327593
TI  - The repeatability of gait speed and physiological cost index measurements in
      working adults.
AB  - OBJECTIVES: To determine the performance characteristics of gait speed
      measurements and the physiological cost index (PCI; heart rate change/gait speed)
      in working adults. METHODS: Gait speeds, heart rate changes, and non-steady state
      PCIs were calculated in 61 volunteers who worked in our health sciences center.
      These subjects completed 9 separate 100-foot walk tests in 3 separate sessions.
      RESULTS: The mean heart rate change after a 100-foot walk was 16.6 +/- 8.1 beats
      per minute. The mean gait speed was 76.1 +/- 9.6 meters per minute, and the mean
      PCI was 0.22 +/- 0.11 beats per meter. There were highly significant correlations
      among all measurements on the 9 separate tests (correlation coefficients 0.41
      0.95); gait speed measurements had the highest correlations (0.91-0.95). In a
      multivariable model hypertension and arthritis were associated with reduced gait
      speeds. CONCLUSION: Gait speed, heart rate changes, and non-steady state PCIs
      have good repeatability when measured over short walks. This information provides
      a rapid physiological assessment and a method for measuring changes in functional
      status in healthy subjects and most patients.

PMID- 24327594
TI  - Severe obesity and high blood pressure among children, Philadelphia health
      centers, 2010.
AB  - BACKGROUND: Child obesity is a major health problem particularly affecting
      disadvantaged population groups. Severe obesity carries additional health risks
      for children. In the context of the childhood obesity epidemic, high blood
      pressure among children is of increasing concern. METHODS: Chart reviews were
      carried out to examine the prevalence of severe obesity and its association with
      high blood pressure measurements among randomly selected patients aged 3 to 17
      years who had well-child care visits at 8 public community health centers during
      2010. RESULTS: A majority of the 691 patients reviewed were African American
      (58%); an additional 16% were Hispanic. The prevalence of severe obesity was 7.7%
      (95% confidence interval = 5.8% to 9.9%) and the prevalence of high blood
      pressure measurements was 17.5% (95% confidence interval = 14.8% to 20.6%).
      Patients who were severely obese were more than twice as likely as other children
      to have high blood pressure values. CONCLUSIONS: Severe obesity is associated
      with substantially increased frequency of high blood pressure measurements in
      children, and should be investigated further as a potential marker for
      hypertension in children. Primary care providers should be prepared to diagnose
      and treat hypertension in severely obese children.

PMID- 24327596
TI  - Mental health integration: normalizing team care.
AB  - This article examines the impact of integrating mental health into primary health
      care. Mental Health Integration (MHI) within Intermountain Healthcare has changed
      the culture of primary health care by standardizing a team-based care process
      that includes mental health as a normal part of the routine medical encounter.
      Using a quantitative statistical analysis of qualitative reports (mixed methods
      study), the study reports on health outcomes associated with MHI for patients and
      staff. Researchers interviewed 59 patients and 50 staff to evaluate the impact of
      MHI on depression care. Patients receiving MHI reported an improved relationship
      with caregivers (P < .001) and improved overall functioning in their lives (P <
      .01). Staff providing care in MHI reported that patients experienced improved
      access to mental health care, improved overall patient productivity in daily
      functions (P < .01), and access to team care (P < .001). As MHI became routine,
      patients discussed complementary team interventions more frequently (P < .0001).
      Mental health problems rank second in chronic disease today. MHI offers promising
      results for improving the quality and cost of effective treatment for chronic
      disease. This research provides guidelines for organizing mental health care,
      staff productivity, and patient satisfaction, using a team approach to improve
      outcomes. 

PMID- 24327595
TI  - African american primary care physicians' prostate cancer screening practices.
AB  - INTRODUCTION: Prostate cancer is the most common cancer and the second leading
      cause of cancer death among men in the United States. African American (AA) men
      have greater prostate cancer burden than other men. Little is known about AA
      primary care physicians' (PCPs) practices regarding prostate cancer screening.
      METHODS: We analyzed data from the 2007-2008 National Survey of Primary Care
      Physicians' Practices Regarding Prostate Cancer Screening. The current study
      included 604 AA PCPs. Outcomes assessed were (a) offering screening using the
      prostate-specific antigen (PSA) test, (b) use of screening discussions to involve
      patients in the decision to screen, and (c) having a discussion policy to try to
      talk the patient into getting the screening tests. RESULTS: Most AA PCPs were
      male (52%), younger than 50 years (61%), and had 21% to 100% AA patients in their
      practices (74%). The majority (94%) of AA PCPs offered prostate cancer screening
      using PSA, discussed the tests with their male patients to involve them in the
      decision to screen (83%), and had a policy to try to talk the patient into
      getting the screening tests (77%). Multivariate analysis showed that offering
      screening, use of discussions, and a usual policy to encourage taking the
      screening tests varied mainly by practice-related factors, including practice
      type, practice location, and percentage of AA patients in the practice.
      CONCLUSION: Data from this study indicate that most AA PCPs reported high
      proscreening behaviors for all 3 outcomes. Additionally, practice- and screening
      related factors may be important when examining AA PCP screening behaviors.

PMID- 24327597
TI  - Implementation of the Connective Tissue Screening Questionnaire in northeast
      Pennsylvania to identify comorbidities of connective tissue diseases in subjects
      with systemic lupus erythematosus.
AB  - Previous studies have described an increased risk of developing an additional
      connective tissue disease (CTD) when one such ailment is present. We examine here
      the likelihood that individuals with systemic lupus erythematosus (SLE) screen
      positive for one or more of the following five autoimmune CTDs: Sjogren's
      syndrome, scleroderma, rheumatoid arthritis, dermatomyositis/polymyositis, and
      mixed connective tissue disorder. Five hundred SLE-diagnosed subjects were asked
      to complete a CTD screening questionnaire (CSQ). The results were analyzed
      according to the set of diagnostic criteria given by the American College of
      Rheumatology to identify probable cases of each CTD. Significant standardized
      prevalence ratios and comorbidities indicate an increased risk for the other
      autoimmune CTDs. In all, 96% of the subjects screened positive for at least one
      additional CTD, and 13% screened positive for at least two additional CTDs. We
      see that the SLE-diagnosed population may benefit from further attention
      regarding the presence of additional CTDs, which may further inform treatment
      strategies. We also see the application of the CSQ as a potentially important
      tool for clinical practice, and we describe the present study's limitations along
      with possible ways that these can be addressed. 

PMID- 24327598
TI  - Future complexity of care tier affected by depression outcomes.
AB  - BACKGROUND: The inclusion of mental health issues in the evaluation of
      multimorbidity generally has been as the presence or absence of the condition
      rather than severity, complexity, or stage. The hypothesis for this study was
      that clinical outcome of the depression 6 months after enrollment into
      collaborative care management would have a role in predicting future complexity
      of care tier. METHODS: This study was a retrospective chart review of 1894
      primary care patients who were diagnosed with major depressive disorder or
      dysthymia as of December 2012. Multiple logistic regression analysis was used to
      test the independent associations between each variable and the odds of being
      included in the higher tiers (HT) group. RESULTS: Age (odds ratio [OR] = 1.022,
      confidence interval [CI] = 1.013-1.030, P < .001), female gender (OR = 1.380, CI
      = 1.020-1.868, P = .037), being married (OR = 0.730, CI = 0.563-0.947, P = .018),
      and the presence of comorbidities (1, OR = 1.986, CI = 1.485-2.656, P < .001; >=
      2, OR = 4.678, CI = 3.242-6.750, P < .001) were independently associated with
      future HT levels. The presence of persistent depressive symptoms (PHQ-9 >= 10) at
      6 months conferred 2.280 (CI = 1.673-3.107, P < .001) times likely odds of HT
      level compared with clinical remission at 6 months. CONCLUSION: Patients with the
      diagnosis of major depression or dysthymia had greater odds of complex tier
      levels in the future, if depression was not treated to remission by 6 months.
      This study demonstrated the importance of the goal of significant improvement
      (ie, remission) of depression symptoms by 6 months (especially those older
      patients with more comorbidity) from entering into the higher complexity tiers.

PMID- 24327599
TI  - Well-child care clinical practice redesign at a community health center: provider
      and staff perspectives.
AB  - BACKGROUND: Community health centers (CHCs) are a key element of the health care
      safety net for underserved children. They may be an ideal setting to create well
      child care (WCC) clinical practice redesign to drastically improve WCC delivery.
      OBJECTIVE: To examine the perspectives of clinical and administrative staff at a
      large, multisite urban CHC on alternative ways to deliver WCC services for low
      income children aged 0 to 3 years. METHODS: Eight semistructured interviews were
      conducted with 4 pediatric teams (each consisting of 1 pediatrician and 2 medical
      assistants) and 4 CHC executive/administrative staff (Medical Director, COO, CEO,
      and Nurse Supervisor). Discussions were recorded, transcribed, and analyzed using
      the constant comparative method of qualitative analysis. Salient themes included
      WCC delivery challenges and endorsed WCC clinical practice redesign solutions.
      RESULTS: The 3 main WCC delivery challenges included long wait times due to
      insurance verification and intake paperwork, lack of time for parent education
      and sick visits due to WCC visit volume, and absence of a system to encourage
      physicians to use non-face-to-face communication with parents. To address WCC
      delivery challenges, CHC providers and administrators endorsed several options
      for clinical practice redesign in their setting. These included use of a health
      educator in a team-based model of care, a previsit tool for screening and
      surveillance, Web site health education, a structured system for non-face-to-face
      (eg, phone) parent communication, and group visits. CONCLUSION: CHC-specific
      strategies for WCC clinical practice redesign endorsed by a large, multisite
      safety net clinic may lead to more efficient, effective, and family-centered WCC
      for low-income populations.

PMID- 24327600
TI  - Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy
      males.
AB  - The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists
      have been linked to the release of atrial natriuretic peptide (ANP) in mice.
      Whether a GLP1-ANP axis exists in humans is unknown. In this study, we examined
      12 healthy young males in a randomized, controlled, double-blinded, single-day,
      cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma
      proANP concentrations were measured by an automated mid-region-directed proANP
      immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular
      E170. Urine was collected for measurements of sodium excretion. Although GLP1
      infusion increased the urinary sodium excretion markedly, there were no
      significant changes in either proANP or proBNP concentrations. When GLP1 infusion
      was stopped, sodium excretion declined rapidly. As proANP concentration reflects
      ANP secretion, our data could not confirm the existence of a GLP1-ANP axis in
      humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated
      exclusively via ANP. 

PMID- 24327601
TI  - Effect of i.p. insulin administration on IGF1 and IGFBP1 in type 1 diabetes.
AB  - In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high
      concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been
      suggested that these abnormalities in the GH-IGF1 axis are due to low insulin
      concentrations in the portal vein. We hypothesized that the i.p. route of insulin
      administration increases IGF1 concentrations when compared with the s.c. route of
      insulin administration. IGF1 and IGFBP1 concentrations in samples derived from an
      open-label, randomized cross-over trial comparing the effects of s.c. and i.p.
      insulin delivery on glycaemia were determined. T1DM patients were randomized to
      receive either 6 months of continuous i.p. insulin infusion (CIPII) through an
      implantable pump (MIP 2007C, Medtronic) followed by 6 months of s.c. insulin
      infusion or vice versa with a washout phase in between. Data from 16 patients who
      had complete measurements during both treatment phases were analysed. The change
      in IGF1 concentrations during CIPII treatment was 10.4 MUg/l (95% CI -0.94, 21.7
      MUg/l; P=0.06) and during s.c. insulin treatment was -2.2 MUg/l (95% CI -13.5,
      9.2 MUg/l; P=0.69). When taking the effect of treatment order into account, the
      estimated change in IGF1 concentrations was found to be 12.6 MUg/l (95% CI -3.1,
      28.5 MUg/l; P=0.11) with CIPII treatment compared with that with s.c. insulin
      treatment. IGFBP1 concentrations decreased to -100.7 MUg/l (95% CI -143.0, -58.3
      MUg/l; P<0.01) with CIPII treatment. During CIPII treatment, parts of the GH-IGF1
      axis changed compared with that observed during s.c. insulin treatment. This
      supports the hypothesis that the i.p. route of insulin administration is of
      importance in the IGF1 system. 

PMID- 24327602
TI  - Adipose-derived Mesenchymal Stem Cells (ASCs) may favour breast cancer recurrence
      via HGF/c-Met signaling.
AB  - Adipose tissue is a reservoir of Mesenchymal Stem Cells (Adipose-derived
      Mesenchymal Stem Cells, ASCs), endowed with regenerative properties. Fat graft
      was proposed for breast reconstruction in post-surgery cancer patients achieving
      good aesthetic results and tissues regeneration. However, recent findings
      highlight a potential tumorigenic role that ASCs may have in cancer recurrence,
      raising some concerns about their safety in clinical application. To address this
      issue, we established a model where autologous ASCs were combined with primary
      normal or cancer cells from breast of human donors, in order to evaluate
      potential effects of their interactions, in vitro and in vivo. Surprisingly, we
      found that ASCs are not tumorigenic per se, as they are not able to induce a
      neoplastic transformation of normal mammary cells, however they could exhacerbate
      tumorigenic behaviour of c-Met-expressing breast cancer cells, creating an
      inflammatory microenvironment which sustained tumor growth and angiogenesis.
      Pharmacological c-Met inhibition showed that a HGF/c-Met crosstalk between ASCs
      and breast cancer cells enhanced tumor cells migration, acquiring a metastatic
      signature, and sustained tumor self-renewal. The master role of HGF/c-Met pathway
      in cancer recurrence was further confirmed by c-Met immunostaining in primary
      breast cancer from human donors, revealing a strong positivity in patients
      displaying a recurrent pathology after fat grafts and a weak/moderate staining in
      patients without signs of recurrence. Altogether our findings, for the first
      time, suggest c-Met expression, as predictive to evaluate risk of cancer
      recurrence after autologous fat graft in post-surgery breast cancer patients,
      increasing the safety of fat graft in clinical application. 

PMID- 24327603
TI  - Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin
      Eg5.
AB  - Kinesin motor proteins exert essential cellular functions in all eukaryotes. They
      control mitosis, migration and intracellular transport through interaction with
      microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a
      promising new class of anti-neoplastic agents currently evaluated in clinical
      cancer trials for solid tumors and hematological malignancies. Here we report
      induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon
      stimulation of in vivo angiogenesis with vascular endothelial growth factor-A
      (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding
      genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of
      Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis
      independent vascular outgrowth in aortic ring cultures is strongly impaired after
      Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function
      causes developmental and vascular defects in zebrafish and chick embryos and
      potent inhibition of tumor angiogenesis in experimental tumor models. Besides
      blocking tumor cell proliferation, impairing endothelial function is a novel
      mechanism of action of kinesin inhibitors. 

PMID- 24327605
TI  - Effect of Cyp27A1 gene dosage on atherosclerosis development in ApoE-knockout
      mice.
AB  - In humans, sterol 27-hydroxylase (CYP27A1) deficiency leads to cholesterol
      deposition in tendons and vasculature. Thus, in addition to its role in bile acid
      synthesis, where it converts cholesterol to 27-hydroxycholesterol (27-OHC),
      CYP27A1 may also be atheroprotective. Cyp27A1-deficient (Cyp27A1(-/-)) mice were
      crossed with apolipoprotein E (apoE)-deficient mice. Cyp27A1(+/+)/apoE(-/-) [ApoE
      knockout (KO)], Cyp27A1(+/-)/apoE(-/-) heterozygous (het), and Cyp27A1(-/-)/apoE(
      /-) [double-knockout (DKO)] mice were challenged with a Western diet (WD) for 3
      and 6 mo. ApoE-KO mice fed a chow diet or a WD were used as the control. The
      severity of atherosclerosis in DKO mice was reduced 10-fold. Compared with the
      control, the DKO mice had no 27-OHC, total plasma cholesterol and low-density
      lipoprotein and very low density lipoprotein (LDL/VLDL) concentrations were
      reduced 2-fold, and HDL was elevated 2-fold. Expression of hepatic CYP7A1, CYP3A,
      and CYP8B1 were 5- to 10-fold higher. 3-Hydroxy-3-methyl-glutaryl-CoA reductase
      (HMGR) activity increased 4-fold. Fecal cholesterol was increased. In contrast,
      het mice fed a WD developed accelerated atherosclerosis and severe skin lesions,
      possibly because of reduced reverse cholesterol transport due to diminished 27
      OHC production. CYP27A1 activity is involved in the control of cholesterol
      homeostasis and development of atherosclerosis with a distinct gene dose
      dependent effect.

PMID- 24327606
TI  - Unexpected low-dose toxicity of the universal solvent DMSO.
AB  - Dimethyl sulfoxide (DMSO) is an important aprotic solvent that can solubilize a
      wide variety of otherwise poorly soluble polar and nonpolar molecules. This,
      coupled with its apparent low toxicity at concentrations <10%, has led to its
      ubiquitous use and widespread application. Here, we demonstrate that DMSO induces
      retinal apoptosis in vivo at low concentrations (5 MUl intravitreally dosed DMSO
      in rat from a stock concentration of 1, 2, 4, and 8% v/v). Toxicity was confirmed
      in vitro in a retinal neuronal cell line, at DMSO concentrations >1% (v/v), using
      annexin V, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL),
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and
      AlamarBlue cell viability assays. DMSO concentrations >10% (v/v) have recently
      been reported to cause cellular toxicity through plasma membrane pore formation.
      Here, we show the mechanism by which low concentrations (2-4% DMSO) induce
      caspase-3 independent neuronal death that involves apoptosis-inducing factor
      (AIF) translocation from mitochondria to the nucleus and poly-(ADP-ribose)
      polymerase (PARP) activation. These results highlight safety concerns of using
      low concentrations of DMSO as a solvent for in vivo administration and in
      biological assays. We recommend that methods other than DMSO are employed for
      solubilizing drugs but, where no alternative exists, researchers compute absolute
      DMSO final concentrations and include an untreated control group in addition to
      DMSO vehicle control to check for solvent toxicity.

PMID- 24327604
TI  - Drug resistance in multiple myeloma: latest findings and new concepts on
      molecular mechanisms.
AB  - In the era of new and mostly effective therapeutic protocols, multiple myeloma
      still tends to be a hard-to-treat hematologic cancer. This hallmark of the
      disease is in fact a sequel to drug resistant phenotypes persisting initially or
      emerging in the course of treatment. Furthermore, the heterogeneous nature of
      multiple myeloma makes treating patients with the same drug challenging because
      finding a drugable oncogenic process common to all patients is not yet feasible,
      while our current knowledge of genetic/epigenetic basis of multiple myeloma
      pathogenesis is outstanding. Nonetheless, bone marrow microenvironment components
      are well known as playing critical roles in myeloma tumor cell survival and
      environment-mediated drug resistance happening most possibly in all myeloma
      patients. Generally speaking, however; real mechanisms underlying drug resistance
      in multiple myeloma are not completely understood. The present review will
      discuss the latest findings and concepts in this regard. It reviews the
      association of important chromosomal translocations, oncogenes (e.g. TP53)
      mutations and deranged signaling pathways (e.g. NFkappaB) with drug response in
      clinical and experimental investigations. It will also highlight how bone marrow
      microenvironment signals (Wnt, Notch) and myeloma cancer stem cells could
      contribute to drug resistance in multiple myeloma. 

PMID- 24327608
TI  - Normative values for corneal densitometry analysis by Scheimpflug optical
      assessment.
AB  - PURPOSE: To describe the normative data for corneal Scheimpflug densitometry
      based on a cohort of normal participants. METHODS: A total of 445 healthy
      participants were recruited for assessment (794 eyes). Left and right eyes were
      considered separately. All participants were assessed using the corneal
      densitometry analysis add-on to the standard software of the Oculus Pentacam.
      Densitometry measurements were obtained and expressed in standardized grayscale
      units (GSU). RESULTS: All participants were Caucasian; 42% were male and 58% were
      female. The mean age was 48.0 +/- 15.3 years (range, 20.2-84.2 years). Mean
      corneal densitometry over the 12-mm-diameter area was 19.74 +/- 3.89 GSU. When
      divided by radial zone, densitometry values were lowest in the central zone
      (16.76 +/- 1.87 GSU) and highest in the periphery (27.36 +/- 7.47 GSU). There was
      no difference between central zone and the surrounding 2- to 6-mm annulus (P >
      0.05), though the 6- to 10-mm and the 10- to 12-mm zones displayed higher
      densitometry values (P < 0.001). When divided by depth, the anterior layer
      displayed the highest densitometry reading of 25.81 +/- 5.14 GSU, which was
      significantly higher than that of both the central (P < 0.001) and the posterior
      layers (P < 0.001). Changes in corneal densitometry were correlated with age,
      though not within the central 6-mm-diameter ring. No sex difference was seen
      within the cohort. CONCLUSIONS: This add-on to the standard imaging software
      allows rapid and objective assessment of the corneal densitometry. We provide
      normative data that may be used as a reference facilitating research and
      complementing clinical examination.

PMID- 24327607
TI  - Regulatory circuitry of TWEAK-Fn14 system and PGC-1alpha in skeletal muscle
      atrophy program.
AB  - Skeletal muscle wasting attributed to inactivity has significant adverse
      functional consequences. Accumulating evidence suggests that peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and TNF
      like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal
      muscle mass in various catabolic states. While the activation of TWEAK-Fn14
      signaling causes muscle wasting, PGC-1alpha preserves muscle mass in several
      conditions, including functional denervation and aging. However, it remains
      unknown whether there is any regulatory interaction between PGC-1alpha and TWEAK
      Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly
      reduces the levels of PGC-1alpha and mitochondrial content (~50%) in skeletal
      muscle. Levels of PGC-1alpha are significantly increased in skeletal muscle of
      TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation.
      Transgenic (Tg) overexpression of PGC-1alpha inhibited progressive muscle wasting
      in TWEAK-Tg mice. PGC-1alpha inhibited the TWEAK-induced activation of NF-kappaB
      (~50%) and dramatically reduced (~90%) the expression of atrogenes such as MAFbx
      and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1alpha also
      prevented the inducible expression of Fn14 in denervated skeletal muscle.
      Collectively, our study demonstrates that TWEAK induces muscle atrophy through
      repressing the levels of PGC-1alpha. Overexpression of PGC-1alpha not only blocks
      the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in
      denervated skeletal muscle.

PMID- 24327609
TI  - Swine cone and rod precursors arise sequentially and display sequential and
      transient integration and differentiation potential following transplantation.
AB  - PURPOSE: We followed cone and rod development in the pig and we correlated
      development with the potential for cone and rod precursor integration and
      differentiation following subretinal transplantation. METHODS: Rod and cone
      precursors were identified during development by their position in the outer
      retina and by immunostaining for markers of differentiation. Embryonic retinal
      cells from green fluorescent protein (GFP)(+) transgenic pigs at different
      developmental stages were transplanted into adult retinas and integration and
      differentiation was followed and quantified by immunostaining for markers of cone
      and rod differentiation. RESULTS: Pig cones and rods are spatially segregated,
      allowing us to follow rod and cone development in situ. Gestation in the pig is
      114 days. By embryonic day (E) 50, postmitotic cone progenitors had formed the
      outer two rows of the retina. These cone progenitors are marked by expression of
      Islet1 (ISL1) and Recoverin (RCVRN) (at this embryonic stage, RCVRN exclusively
      marks these cone precursors). By contrast, postmitotic neural retina leucine
      zipper (NRL)(+) rod precursors, located interior to the cone precursors, did not
      appear until E65. At E50, before NRL(+) rod precursors are evident, transplanted
      cells gave rise almost exclusively to cones. At, E57, transplanted cells gave
      rise to equal numbers of rods and cones, but by E65, transplanted cells gave rise
      almost exclusively to rods. Transplantation of cells at E85 or E105, as
      precursors initiate opsin expression, led to few integrated cells. CONCLUSIONS:
      Consistent with their sequential appearances in embryonic retina, these results
      demonstrate sequential and surprisingly narrow developmental windows for
      integration/differentiation of cone and rod precursors following transplantation.

PMID- 24327610
TI  - Retinal vessel tortuosity associated with central retinal vein occlusion: an
      optical coherence tomography study.
AB  - PURPOSE: We studied morphologic changes of the retinal vasculature in eyes with
      central retinal vein occlusion (CRVO) through the use of optical coherence
      tomography (OCT). METHODS: Major retinal vessels in 35 eyes from 35 consecutive
      patients with acute CRVO were examined prospectively and longitudinally with
      sequential thin sectioning and circumpapillary scanning. Anteroposterior venous
      tortuosity associated with CRVO was quantified on longitudinal OCT images of a
      randomly selected major temporal vein. On OCT sections of a given vein, we
      identified the innermost and outermost points of the vessel wall. The degree of
      anteroposterior venous tortuosity was defined as the difference between the
      vertical distances from the retinal pigment epithelium to the center of the
      venous lumen at these two points. RESULTS: The OCT images revealed that the major
      retinal veins traveled tortuously through the swollen neurosensory retina from
      the inner retinal surface to the retinal pigment epithelium. The degree of
      anteroposterior venous tortuosity was correlated with poor visual acuity (r =
      0.457, P = 0.017), increased mean foveal thickness (r = 0.671, P < 0.001), and
      the height of foveal detachment (r = 0.414, P = 0.032). In 4 (11%) eyes, a
      localized retinal detachment was detected around the optic disc, which correlated
      with anteroposterior venous tortuosity. In 14 (40%) eyes, elongated major retinal
      veins disrupted the boundary between retinal vessels and parenchyma, which
      resulted in juxtavenous splitting of the neurosensory retina. CONCLUSIONS: In
      eyes with CRVO, OCT can be used to visualize anteroposterior venous tortuosity
      and associated structural changes to the retinal parenchyma.

PMID- 24327611
TI  - Results of a patient-directed survey on frequency of family history of glaucoma
      in 2170 patients.
AB  - PURPOSE: To evaluate in different types of glaucoma frequency of family history
      of glaucoma (FHG), age at diagnosis, glaucoma risk in relatives, and acceptance
      rate of genetic glaucoma tests. To assess stage of visual field loss (VFL) in
      relation to FHG. METHODS: Using standardized questions whether an ophthalmologist
      had found or excluded glaucoma or ocular hypertension (OH), 2170 patients with
      glaucoma or OH interviewed all their first and second degree relatives. One
      thousand three hundred thirty-eight patients had POAG, 233 primary angle closure
      glaucoma (PACG), 148 OH, 153 normal tension glaucoma (NTG), 50 pigmentary
      glaucoma (PG), and 66 pseudoexfoliation glaucoma (PEX). RESULTS: Frequency of FHG
      was 40% in POAG, without significant differences compared with NTG (P = 0.08), OH
      (P = 0.5), PACG (P = 0.4), and PG (P = 0.6). There were significant differences
      in age at diagnosis between the glaucomas (smallest between group P < 0.0001).
      Patients with FHG were significantly younger at diagnosis than patients without
      FHG in all types of glaucoma (all P values <= 0.03), except NTG and PEX.
      Patients' siblings and mothers had the highest detection probability for glaucoma
      in POAG and OH. There was no significant relation between stage of VFL and FHG in
      POAG (P = 0.6). Sixty-eight percent of patients would participate in genetic
      glaucoma tests. CONCLUSIONS: There is a similarly high genetic disposition in all
      types of glaucoma. Disease risk was especially high in mothers and siblings. In
      patients with FHG, knowledge of genetic disposition of the glaucomas may have led
      to earlier diagnosis. This highlights the need for glaucoma awareness campaigns.

PMID- 24327612
TI  - The ocular surface phenotype of Muc5ac and Muc5b null mice.
AB  - PURPOSE: Recent development of mice null for either Muc5ac or Muc5b mucin allows
      study of their specific roles at the mouse ocular surface. A recent report
      indicated that Muc5ac null mice show an ocular surface phenotype similar to that
      seen in dry eye syndrome. The purpose of our study was to determine the effect of
      lack of Muc5ac or Muc5b on the ocular surface, and to determine if environmental
      desiccating stress exacerbated a phenotype. METHODS: Muc5ac null and Muc5b null
      mice, and their wild-type controls were examined for ocular surface defects by
      fluorescein staining. The number of goblet cells per area of conjunctival
      epithelium was counted, and levels of mucin gene expression and genes associated
      with epithelial stress, keratinization, and differentiation, known to be altered
      in dry eye syndrome, were assayed. To determine if the null mice would respond
      more to desiccating stress than their wild-type controls, they were challenged in
      a controlled environment chamber (CEC) and assessed for changes in fluorescein
      staining, tear volume, and inflammatory cells within the conjunctival and corneal
      epithelia. RESULTS: Unlike the previous study, we found no ocular surface
      phenotype in the Muc5ac null mice, even after exposure to desiccating
      environmental stress. Similarly, no ocular surface phenotype was present in the
      Muc5b null mice, either before or after exposure to a dry environment in the CEC.
      CONCLUSIONS: Our results indicate that deleting either the Muc5ac or Muc5b gene
      is insufficient to create an observable dry eye phenotype on the ocular surface
      of these mice.

PMID- 24327613
TI  - Effect of nerve growth factor on the in vitro induction of apoptosis of human
      conjunctival epithelial cells by hyperosmolar stress.
AB  - PURPOSE: To evaluate the effects of nerve growth factor (NGF), which is activated
      during inflammatory episodes of ocular diseases, on the apoptotic response in
      cultured human primary conjunctival epithelial cells (pHCECs). METHODS: Levels of
      NGF transcripts and NGF protein in pHCEC grown in medium with normal osmolarity
      (307 mOsm/L) or hyperosmolar medium (350, 400, and 450 mOsm/L) were determined
      using RT-PCR or ELISA, respectively. To assess apoptosis, pHCEC were cultured in
      normal or 400 mOsm/L hyperosmolar medium with neutralizing anti-NGF antibody or
      recombinant human NGF for 6 hours before analysis by flow cytometry. Levels of
      Bcl-xL, Bax, phosphorylated JNK, and cleaved caspase-3 were detected using
      Western blotting. Levels of the inflammatory cytokine IL-6 was analyzed using
      ELISA. RESULTS: Hyperosmolar conditions increased NGF levels in cultured pHCECs.
      Hyperosmolarity and exposure to neutralizing anti-NGF antibody significantly
      increased the number of apoptotic cells. Addition of recombinant human NGF to 400
      mOsm/L medium decreased the number of apoptotic cells, reduced the expression of
      phosphorylated JNK, Bax, and cleaved caspase-3 and increased the expression of
      Bcl-xL. Levels of IL-6 were increased by hyperosmotic stress but decreased by
      exposure to recombinant human NGF. CONCLUSIONS: Hyperosmolarity induces apoptosis
      of pHCECs by activating JNK signaling. Increased levels of NGF under hyperosmolar
      conditions may contribute, at least in part, to the reduced apoptosis of pHCECs
      and may be beneficial in recovering conjunctival damage due to chronic
      hyperosmolar stress.

PMID- 24327614
TI  - Suggestive association with ocular phoria at chromosome 6p22.
AB  - PURPOSE: We conducted a genome-wide association study to identify genetic factors
      that contribute to the etiology of heterophoria. METHODS: We measured near and
      far vertical and horizontal phorias in 988 healthy adults aged 16 to 40 using the
      Keystone telebinocular with plates 5218 and 5219. We regressed degree of phoria
      against genotype at 642758 genetic loci. To control for false positives, we
      applied the conservative genome-wide permutation test to our data. RESULTS: A
      locus at 6p22.2 was found to be associated with the degree of near horizontal
      phoria (P = 2.3 * 10(-8)). The P value resulting from a genome-wide permutation
      test was 0.014. CONCLUSIONS: The strongest association signal arose from an
      intronic region of the gene ALDH5A1, which encodes the mitochondrial enzyme
      succinic semialdehyde dehydrogenase (SSADH), an enzyme involved in gamma
      aminobutyric acid metabolism. Succinic semialdehyde dehydrogenase deficiency,
      resulting from mutations of ALDH5A1, causes a variety of neural and behavioral
      abnormalities, including strabismus. Variation in ALDH5A1 is likely to contribute
      to degree of horizontal phoria.

PMID- 24327615
TI  - Neuropeptides released from trigeminal neurons promote the stratification of
      human corneal epithelial cells.
AB  - PURPOSE: To examine the effects of neural cells on the stratification of and
      junctional protein expression by corneal epithelial cells with a coculture
      system. METHODS: PC12 cells induced to undergo neuronal differentiation or rat
      trigeminal nerve cells were cultured together with simian virus 40-transformed
      human corneal epithelial (HCE) cells on opposite sides of a collagen vitrigel
      membrane. Stratification of HCE cells was examined by immunofluorescence analysis
      with antibodies to zonula occludens-1. Expression of junctional proteins in HCE
      cells was assessed by RT-PCR and immunoblot analyses. RESULTS: The presence of
      neural cells (PC12 cells or trigeminal neurons) markedly promoted the
      stratification of HCE cells as well as increased the amounts of N-cadherin mRNA
      and protein in these cells. These effects of the neural cells were mimicked by
      conditioned medium prepared from differentiating PC12 cells or by the
      neuropeptides substance P and calcitonin gene-related peptide (CGRP).
      Furthermore, the stimulatory effects of trigeminal neurons on the stratification
      of and N-cadherin expression by HCE cells were inhibited by antagonists of
      substance P or of CGRP. CONCLUSIONS: These results suggest that trigeminal
      neurons play an important role in the differentiation of corneal epithelial
      cells. Neuropeptides released from these neurons may thus regulate adhesion
      between corneal epithelial cells and thereby contribute to the establishment and
      maintenance of corneal structure and function.

PMID- 24327616
TI  - Accuracy of rural refractionists in western China.
AB  - PURPOSE: We assessed the prevalence and predictors of inaccurate refractive error
      among rural refractionists in western China. METHODS: A subset of primary school
      children with visual acuity (VA) <=6/12 in >=1 eye, undergoing subjective
      refinement by local refractionists after cycloplegic autorefraction in an ongoing
      population-based study, received repeat refraction by university optometrists for
      quality control. RESULTS: Among 502 children (mean age 10.5 years, 53.2% girls),
      independent predictors of poor (inaccurate by >=1.0 diopter [D]) refraction by 21
      rural practitioners (66.7% with high school or lower education) included
      hyperopia (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.4-7.3, P <
      0.001), astigmatism (OR = 3.8; 95% CI, 2.5-5.6; P < 0.001) and VA uncorrectable
      to >6/12 by the rural refractionist (OR = 4.7; 95% CI, 3.1-7.3; P = < 0.001).
      Among 201 children whose vision was uncorrectable in >=1 eye by the rural
      refractionists, vision could be improved to >6/12 by the university optometrist
      in 110 (54.7%). We estimate vision could be so improved in 9.1% of all children
      refracted by these rural refractionists. A reason for inaccuracy in this setting
      is the erroneous tendency of rural refractionists to adjust instrument values for
      accommodation, even under cycloplegia. CONCLUSIONS: Rural refractionists in
      western China have little formal training and frequently fail to optimize VA
      among children, even when autorefractors are used. Training is needed emphasizing
      better use of automated refraction, particularly in children with astigmatism and
      hyperopia.

PMID- 24327618
TI  - Macular microstructures and prognostic factors in myopic subretinal hemorrhages.
AB  - PURPOSE: To investigate microstructural changes and visual prognosis in myopic
      subretinal hemorrhages (mSH) without choroidal neovascularization (CNV). METHODS:
      In this retrospective, observational case series, 13 consecutive eyes with mSH
      were followed for 6 months. The medical records, fluorescein angiography (FA),
      and spectral-domain optical coherence tomography (OCT) were reviewed. Fluorescein
      angiography confirmed the absence of CNV. The baseline and 6-month
      findings/parameters were investigated, including the maximal hemorrhagic height,
      intraretinal hyperscattering signal across the retina at 6 months (i.e.,
      intraretinal hyperreflective sign), and integrity of the photoreceptor inner and
      outer segment (IS/OS) and external limiting membrane (ELM) lines. RESULTS: The
      final visual acuity (VA) improved significantly (P = 0.001), and the hemorrhages
      resolved in 12 (92.3%) eyes by 6 months. The tops of the hemorrhages reached the
      outer nuclear layer (ONL) in three eyes (23.1%), internal limiting membrane (ILM)
      in five (38.5%), and between the two layers in five (38.5%). The intraretinal
      hyperreflective sign in all eyes extended into the ONL in five eyes (38.5%), to
      the ILM in four (30.8%), and between the two layers in four (30.8%). The location
      of the hyperreflective signs at 6 months coincided with the ruptured retinal
      layers at baseline in all eyes. The IS/OS line and the ELM were each intact in
      six (46.2%) eyes. The final VA was associated significantly with the IS/OS (P <
      0.05) and ELM (P < 0.01) integrity. CONCLUSIONS: The intraretinal hyperreflective
      sign, presumed to be scarring that enters through the disrupted outer retina, is
      correlated closely with photoreceptor function.

PMID- 24327617
TI  - The effect of vasopressin on ciliary blood flow and aqueous flow.
AB  - PURPOSE: Previous experiments have shown that arginine-vasopressin (AVP) reduces
      intraocular pressure (IOP) dose-dependently. The present study investigated the
      relationships between IOP, ciliary blood flow (CilBF), and aqueous flow (AqF)
      responses to AVP in anesthetized rabbits. METHODS: CilBF was measured by laser
      Doppler flowmetry and AqF by fluorophotometry. Mean arterial pressure (MAP) and
      IOP were monitored continuously and simultaneously. Perfusion pressure (PP) was
      varied mechanically. Four experimental protocols were performed: the dose
      response (n = 11) and the pressure-flow relationship (n = 8) for CilBF and the
      effects on CilBF, and AqF at low (0.08 ng/kg/min; n = 14) and high AVP infusion
      rates (1.33 ng/kg/min; n = 12). RESULTS: AVP decreased CilBF and IOP dose
      dependently. At the low AVP infusion rate, AqF was reduced by 21.48% +/- 2.52%
      without changing CilBF significantly. The high AVP infusion rate caused a 24.49%
      +/- 3.53% decrease of AqF and a significant reduction in CilBF (35.60% +/-
      3.58%). IOP was reduced by 9.56% +/- 2.35% at low and by 41.02% +/- 3.19% at high
      AVP infusion rates. Based on the Goldmann equation, the decrease of AqF at the
      low AVP infusion rate accounted for 77.1% of the IOP reduction, whereas at the
      high AVP infusion rate, decreased AqF accounted for 28.4% of the IOP decline.
      CONCLUSIONS: The results indicate that AVP can modulate IOP by different dose
      dependent physiological mechanisms. The shifts of the CilBF-AqF relationship
      suggest that the reduction of AqF by the low AVP infusion rate is mainly provoked
      by inhibiting secretory processes in the ciliary epithelium. In contrast, at the
      high AVP infusion rate, the AqF reduction is caused by either reduced CilBF or
      more likely by a combined effect of reduced CilBF and secretory inhibition.

PMID- 24327619
TI  - Medication risk factors associated with healthcare-associated Clostridium
      difficile infection: a multilevel model case-control study among 64 US academic
      medical centres.
AB  - OBJECTIVES: The main objective of this study was to determine patient- and
      hospital-level medication risk factors associated with Clostridium difficile
      infection (CDI) occurrence among patients clustered within hospitals using a
      multilevel model. METHODS: Patients with healthcare-associated (HA)-CDI were
      identified from among 64 academic medical centres in 2009. A frequency match was
      conducted; for each case, up to two controls were selected, matched on similar
      pre-infection length of stay and clinical service line. Patient- and hospital
      level medication use, including antibacterial and gastric acid-suppressant
      agents, was assessed using a two-level logistic regression model. RESULTS: A
      total of 5967 CDI cases and 8167 controls were included in the analysis. The odds
      of acquiring HA-CDI increased with the following medications [OR (95% CI)]: anti
      methicillin-resistant Staphylococcus aureus agents [1.38 (1.22-1.56)]; third- or
      fourth-generation cephalosporins [1.75 (1.62-1.89)]; carbapenems [1.60 (1.44
      1.79)]; beta-lactam/beta-lactamase inhibitor combinations [1.49 (1.36-1.64)];
      vancomycin [1.73 (1.57-1.89)]; and proton pump inhibitors [1.43 (1.30-1.57)]. The
      odds of acquiring HA-CDI decreased with the following medications: clindamycin
      [0.74 (0.63-0.87)]; and macrolides [0.88 (0.77-0.99)]. Controlling for patient
      level covariates, no hospital-level medication covariates that we analysed had
      statistically significant effects on HA-CDI. The odds of acquiring HA-CDI
      increased with the hospital proportion of patients aged >= 65 years [1.01 (1.00
      1.02)]. CONCLUSIONS: We found several medications that were associated with the
      risk of patients developing HA-CDI, including beta-lactam/beta-lactamase
      inhibitor combinations, third- or fourth-generation cephalosporins, carbapenems,
      vancomycin, proton pump inhibitors and anti-methicillin-resistant S. aureus
      agents. There were no medication effects significant at the hospital level.

PMID- 24327620
TI  - Accuracy profile validation of a new analytical method for propane measurement
      using headspace-gas chromatography-mass spectrometry.
AB  - Propane can be responsible for several types of lethal intoxication and
      explosions. Quantifying it would be very helpful to determine in some cases the
      cause of death. Some gas chromatography-mass spectrometry (GC-MS) methods of
      propane measurements do already exist. The main drawback of these GC-MS methods
      described in the literature is the absence of a specific propane internal
      standard necessary for accurate quantitative analysis. The main outcome of the
      following study was to provide an innovative Headspace-GC-MS method (HS-GC-MS)
      applicable to the routine determination of propane concentration in forensic
      toxicology laboratories. To date, no stable isotope of propane is commercially
      available. The development of an in situ generation of standards is thus
      presented. An internal-labeled standard gas (C3DH7) is generated in situ by the
      stoichiometric formation of propane by the reaction of deuterated water (D2O)
      with Grignard reagent propylmagnesium chloride (C3H7MgCl). The method aims to use
      this internal standard to quantify propane concentrations and, therefore, to
      obtain precise measurements. Consequently, a complete validation with an accuracy
      profile according to two different guidelines, the French Society of
      Pharmaceutical Sciences and Techniques (SFSTP) and the Gesellschaft fur
      toxikologische und Forensische Chemie (GTFCh), is presented.

PMID- 24327621
TI  - Accumulation of clenbuterol residues in the hair of Chinese Simmental beef cattle
      during and after treatment.
AB  - The aim of this study was to evaluate the concentrations of clenbuterol residues
      in the red hair of Chinese Simmental beef cattle following exposure to two doses
      of clenbuterol for 21 days. This experiment was conducted in six male red pied
      Chinese Simmental beef cattle which were randomly divided into two groups (n =
      3). Groups 1 and 2 were administered clenbuterol at a dose of 16 and 48 MUg/kg
      body weight (BW)/day, respectively. Hair samples were collected on Days 7, 14 and
      21 during treatment, and on Days 0, 14, 28, 42 and 70 after discontinuation of
      medication, using liquid chromatography tandem mass spectrometry (LC-MS-MS)
      method. About 500 mg hair samples spiked with 50 pg/mg D9-clenbuterol internal
      standard were analyzed with which the method recovery was from 88.6 to 116.9%.
      The results showed that clenbuterol was significantly accumulated in hair, with a
      concentration of 0.98 +/- 0.56 pg/mg in Group 1 and 6.34 +/- 3.21 pg/mg in Group
      2 on Day 7 of treatment, and the residue concentrations increased as treatment
      proceeded. During the early withdrawal period, the residues increased from 13.52
      +/- 8.69 to 17.96 +/- 6.94 pg/mg in Group 1 and from 55.15 +/- 4.04 to 147.79 +/-
      15.35 pg/mg in Group 2. No significant differences were found in the later
      withdrawal period in both treatment groups. The results of the present study
      indicated that the red hair of Chinese Simmental beef cattle has high
      accumulation potential for clenbuterol residues. Hair, as a target matrix, even
      light-pigmented hair, can be used to monitor clenbuterol abuse over a long
      period. 

PMID- 24327622
TI  - Concentrations of cocaine and benzoylecgonine in femoral blood from cocaine
      related deaths compared with venous blood from impaired drivers.
AB  - The concentrations of cocaine and its major metabolite benzoylecgonine (BZE) were
      determined in femoral blood from 132 cocaine-related deaths and compared with
      venous blood from 988 apprehended drivers. Cocaine and BZE were determined by
      solid-phase extraction and isotope dilution gas chromatography-mass spectrometry
      with limits of quantitation of 0.02 mg/L for both substances. Significantly more
      men (95-98%) than women (2-5%) abused cocaine, although their mean age was about
      the same (29-30 years). Mean age (+/-SD) of cocaine-related deaths was 29 +/- 7
      years, which was not significantly different from 30 +/- 8 years in traffic cases
      (P > 0.05). The median concentration of cocaine in blood in 61 fatalities was
      0.10 mg/L compared with 0.06 mg/L in traffic cases (P < 0.001). In drug
      intoxication deaths, the median concentration of cocaine was 0.13 mg/L (N = 25),
      which was not significantly different from 0.09 mg/L (N = 36) in other causes of
      death. Cocaine-related deaths mostly involved mixed drug intoxications including
      co-ingestion of heroin, cannabis, amphetamines as well as legal drugs, such as
      benzodiazepines and/or ethanol. The concentrations of cocaine in blood from
      living and deceased persons overlapped, which makes it infeasible to predict
      toxicity from the analytical toxicology results alone. 

PMID- 24327623
TI  - Surgery for aortic valve disease in teenagers and young adults.

PMID- 24327625
TI  - Methicillin-resistant Staphylococcus aureus in patients with congenital heart
      disease in the pediatric intensive care unit.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization has
      been recognized as a significant problem among hospitalized patients. Available
      data about prevalence of MRSA among children with congenital heart disease (CHD)
      are minimal. The aim of the study was to determine the prevalence of MRSA
      colonization and to identify risk factors for MRSA colonization among children
      <19 years old with CHD admitted to a pediatric intensive care unit (PICU).
      METHODS: Admission and weekly MRSA nasal surveillance testing was performed, and
      patients were stratified into six risk groups based on the Risk Adjustment for
      Congenital Heart Surgery-1 Method. The MRSA-colonized children were compared to
      the MRSA noncolonized children. RESULTS: During the 3-year study period, there
      were 372 admissions of children with CHD to the PICU. Of the 372, 72 (19.4%) had
      no surveillance cultures performed or had no prior history of MRSA and were
      excluded from further analysis. Of the remaining 300 admissions, 29 (9.7%) (263
      individual children) were found to be colonized. The mean age of the 263 children
      when first admitted to the PICU was 3.29 years (range 0.03-18.30, median 0.66).
      Age distribution was not significantly different between the colonized and
      noncolonized groups (P = .236). Gender (P = .667), race (P = .837), and CHD
      complexity (P = .395) were not significantly associated with colonization. The
      odds of being colonized if previously hospitalized were 4.42 times greater than
      if not previously hospitalized (95% confidence interval 1.89, 10.34). CONCLUSION:
      Routine MRSA surveillance should be performed in patients with CHD to identify
      colonized patients.

PMID- 24327626
TI  - Functionally univentricular heart and the fontan operation: lessons learned about
      patterns of practice and outcomes from the congenital heart surgery databases of
      the European association for cardio-thoracic surgery and the society of thoracic
      surgeons.
AB  - BACKGROUND: "The term "functionally univentricular heart" describes a spectrum of
      congenital cardiovascular malformations in which the ventricular mass may not
      readily lend itself to partitioning that commits one ventricular pump to the
      systemic circulation and another to the pulmonary circulation." The purpose of
      this article is to review patterns of practice and outcomes in the Congenital
      Heart Surgery Databases (CHSDBs) of the European Association for Cardio-Thoracic
      Surgery (EACTS) and the Society of Thoracic Surgeons (STS) in patients with
      functionally univentricular hearts undergoing the Fontan operation. METHODS: We
      examined all index operations performed on patients with functionally
      univentricular hearts in the EACTS and STS-CHSDBs over 4 years from 2007 to 2010,
      inclusive. RESULTS: The most common diagnostic categories are hypoplastic left
      heart syndrome, tricuspid atresia, and double inlet left ventricle. The Fontan
      operation makes up 3.2% of all cardiac operations in the EACTS and STS-CHSDBs
      over 4 years from 2007 to 2010, inclusive. Of all the patients undergoing a
      Fontan procedure, 65.1% had an extracardiac Fontan, 21.5% had a lateral tunnel,
      and 5.8% had a Fontan revision or conversion (Re-do Fontan). In operations where
      fenestration status is known, 68.5% of the Fontan operations were fenestrated.
      During the four years of this analysis, only 5 patients had ventricular
      septation. Exclusive of Fontan revision or conversion (Re-do Fontan), all
      remaining Fontan operations had a discharge mortality of 2.3%. Fontan revision or
      conversion (Re-do Fontan) had a discharge mortality of 12.8%. CONCLUSIONS: The
      STS database is largest CHSDB in North America. The EACTS database is largest
      CHSDB in Europe. This review of data from EACTS and STS allows for unique
      documentation of practice patterns and outcomes. From this analysis, it is clear
      that patients with functionally univentricular hearts present a challenging
      problem; however, exclusive of Fontan revision or conversion (Re-do Fontan), the
      Fontan operation has a discharge mortality of 2.3%.

PMID- 24327627
TI  - Innominate artery cannulation and antegrade cerebral perfusion for aortic arch
      reconstruction in infants and children.
AB  - PURPOSE: Innominate artery cannulation has been widely adopted as a means to
      perform aortic arch reconstruction with continuous cerebral perfusion in the
      newborn. Although this technique has been subsequently utilized in infants and
      children, there is currently no data regarding the safety or efficacy in these
      older children. The purpose of this study was to review our experience with
      innominate artery cannulation for aortic arch reconstruction in patients beyond
      the neonatal period. METHODS: This was a retrospective review of 42 infants and
      children who underwent aortic arch reconstruction using the technique of
      innominate artery cannulation with continuous cerebral perfusion. Of these
      procedures, 29 (69%) were primary arch reconstructions, while 13 (31%) were
      aortic arch reoperations. The median age at surgery was 8 months, and 22 patients
      underwent concomitant intracardiac repairs. RESULTS: There was no operative
      mortality in this cohort of 42 patients undergoing aortic arch reconstruction.
      There was also no overt evidence of neurologic injury. Specifically, none of the
      patients demonstrated a neurologic deficit, clinical seizure, or unexpected delay
      in regaining a normal state of consciousness. The median duration of antegrade
      cerebral perfusion was 34 minutes. The median duration of hospital stay was 11
      days. No patient required reoperation on the aortic arch with a median of 45
      month follow-up. CONCLUSIONS: Innominate artery cannulation is a safe and
      effective technique for aortic arch reconstruction in nonneonates. We conclude
      that antegrade cerebral perfusion is a useful technique for aortic arch
      reconstruction in this patient population.

PMID- 24327628
TI  - Bicuspid aortic valves experience increased strain as compared to tricuspid
      aortic valves.
AB  - OBJECTIVE: To determine whether the leaflets of bicuspid aortic valve (BAV)
      experience increased strain when compared to tricuspid aortic valve (TAV)
      leaflets. BACKGROUND: The population at highest risk of aortic valve
      calcification (AVC) are individuals with BAVs. Currently, efforts to medically
      treat AVC are hampered by a limited understanding of the biomechanical forces
      involved in the molecular pathogenesis of AVC. METHODS: Surgically created BAVs
      and control TAVs were placed into a left heart simulator. Strains were calculated
      by comparing the distances between points on the aortic valve (AoV) leaflet
      during various time points during a simulated cardiac cycle. RESULTS: The fused
      leaflets of BAVs experience significantly more strain during systole when
      compared to TAVs. Specifically, BAVs experience 24% strain (P < .0001) in the
      radial direction, parallel to the direction of blood flow, as compared to TAVs.
      There was peak difference of 4% (P < .001) in the circumferential direction.
      DISCUSSION: Based upon the data presented here, we are in the process of
      identifying how increased strain activates calcification-associated pathways in
      AoV cells. Future studies will examine whether these stretch responsive pathways
      can be blocked to inhibit calcification of BAVs.

PMID- 24327629
TI  - Early cyanosis after stage II palliation for single ventricle physiology:
      etiologies and outcomes.
AB  - BACKGROUND: In the early postoperative period after stage II palliation, patients
      with single ventricle physiology can have cyanosis due to a variety of causes.
      This cyanosis can be significant and necessitate cardiac catheterization to
      determine etiology and attempt treatment. Our objective was to determine the
      etiology of early postoperative cyanosis and outcomes in patients referred to the
      catheterization laboratory from the cardiac intensive care unit (CICU) after
      stage II palliation. METHODS: We performed a retrospective analysis of all
      patients referred for cardiac catheterization from the CICU for evaluation of
      early cyanosis after stage II palliation. Etiology for hypoxemia, treatment
      strategy, and patient outcomes were examined for each patient. RESULTS: Between
      January 1, 2006, and December 31, 2011, 244 patients underwent stage II
      palliation of which 22 required cardiac catheterization during the early
      postoperative period because of severe cyanosis. The etiologies for cyanosis were
      venovenous collaterals (n = 12), cavopulmonary pathway thrombosis (n = 3), hemi
      Fontan pathway baffle leak (n = 2), and undetermined (n = 5). Overall, transplant
      free survival to hospital discharge was 50% and survival to hospital discharge
      with stage II physiology was 32%. Venovenous collateral occlusion, cavopulmonary
      anastomosis takedown, and addition of a second source of pulmonary blood flow
      were not associated with improved outcome. CONCLUSIONS: Regardless of the
      etiology or treatment strategy, severe cyanosis in the early postoperative period
      after stage II palliation imparts high mortality and usually indicates failing
      stage II physiology. Venovenous collateral occlusion and thrombectomy are usually
      futile, and those who survive have a low likelihood of having stage II physiology
      at hospital discharge.

PMID- 24327630
TI  - The effect of epinephrine on coronary flow in the setting of a systemic-to
      pulmonary artery shunt.
AB  - BACKGROUND: Indirect clinical evidence suggests that coronary blood flow (CBF) is
      altered in patients palliated with systemic-to-pulmonary artery shunts (SPSs).
      The addition of epinephrine may exert additional effects. METHODS: A total of 11
      newborn piglets underwent placement of a 3.5- to 4-mm graft between the
      innominate artery and the pulmonary artery. Doppler probes measured flow
      continuously in the aorta (aortic flow [AoF]), pulmonary artery and left coronary
      artery at baseline (SPS closed), SPS open, and during epinephrine administration
      (SPS closed and open). Each animal served as its own control. Systolic and
      diastolic CBF, resistance (coronary vascular resistance index [CVRI]), and
      myocardial oxygen supply demand ratio were calculated. RESULTS: Opening the SPS
      increased AoF and decreased systolic and diastolic pressure from baseline, with
      and without the presence of epinephrine. The CBF and CVRI decreased on opening
      the SPS in the presence of epinephrine. The decrease occurred only in diastole
      and was proportional to pulmonary-to-systemic flow ratio (Qp/Qs). Epinephrine
      infusion itself reduced CVRI with SPS closed, but there was little further
      decrease on opening SPS. Myocardial oxygen supply-demand ratio decreased on
      opening SPS at baseline and with epinephrine. CONCLUSIONS: This study suggests
      that SPS decreases CBF, especially in the presence of a higher Qp/Qs and
      epinephrine. The mechanism is largely due to the decrease in diastolic pressure
      and the inability of the coronary arteries to compensate with vasodilation.

PMID- 24327631
TI  - Secondary prophylaxis for rheumatic fever: simple concepts, difficult delivery.
AB  - Registers of those with rheumatic heart disease or a history of acute rheumatic
      fever (RF) are key to prevent RF recurrences and improve disease control.
      Randomized controlled trials show intramuscular long-acting benzathine penicillin
      G is more effective than oral penicillin to prevent recurrences. Although some
      guidelines recommend three-weekly benzathine penicillin, four weekly is effective
      if compliance rates are high. Four-weekly penicillin delivery is also preferable
      to three-weekly regimens for health resource and logistical reasons and for
      patient acceptability and compliance. 

PMID- 24327632
TI  - Aortic cusp extension for surgical correction of rheumatic aortic valve
      insufficiency in children.
AB  - Surgical management of aortic insufficiency in the young is problematic because
      of the lack of an ideal valve substitute. Potential advantages of aortic valve
      repair include low incidences of thromboembolism and endocarditis, avoiding
      conduit replacements, the maintenance of growth potential, and improved quality
      of life. Aortic valve repair is still far from fulfilling the three key factors
      that have allowed the phenomenal development of mitral valve repair
      (standardization, reproducibility, and stable long-term results); however,
      techniques of aortic valve repair have been refined, and subsets of patients
      amenable to repair have been identified. We have focused on the oldest technique
      of aortic valve repair, cusp extension, focusing on children with rheumatic
      aortic insufficiency. Among 77 children operated from 2003 to 2007, there was one
      early death from ventricular failure and one late death from sudden cardiac
      arrhythmia. During a mean follow-up of 12.8 +/- 5.9 years, there were 16 (20.5%)
      reoperations on the aortic valve, at a median of 3.4 years (range, 2 months to
      18.3 years) from repair. Freedom from aortic valve reoperation was 96.2% +/- 2.2%
      at 1 year, 94.9% +/- 2.5% at 2 years, 88.5% +/- 3.6% at 5 years, 81.7% +/- 4.4%
      at 10 years, 79.7% +/- 4.8% at 15 years, and 76.2% +/- 5.7% at 20 years. Although
      aortic cusp extension is technically more demanding, it remains particularly more
      suitable in the context of evolving rheumatic aortic insufficiency in children
      with a small aortic annulus as a bridge surgical approach to late aortic valve
      replacement with a larger valvular prosthesis. 

PMID- 24327633
TI  - Repair options in rheumatic aortic valve disease in young patients: potential
      problems with pericardial cusp extension.
AB  - This article outlines the arguments against cusp extension, which were put
      forward at the debate entitled "Repair options in rheumatic aortic disease in
      young patients" at the Symposium on Surgery for Rheumatic Heart Disease organized
      by The World Society for Pediatric and Congenital Heart Surgery at The Sixth
      World Congress of Paediatric Cardiology and Cardiac Surgery, February 17-22,
      2013, Cape Town, South Africa. We propose that cusp extension should be avoided
      because (1) these patients are usually old enough to receive the same valve
      substitutes as adults, (2) lack of antibioprophylaxis compliance will likely
      result in early reintervention, (3) cusp extension mandates rerepair within four
      to five years and is more expensive in the long term, and (4) it is fraught with
      myocardial ischemic complications. Thus, a mechanical, bioprosthetic, or
      autograft valve replacement may be superior for patients unless they have
      unrestricted access to repetitive interventions. A single surgical technique does
      not suffice in the treatment of rheumatic aortic valve disease, and a diversified
      approach should be adopted dependent on both the patients' characteristics and
      the financial constraints. 

PMID- 24327634
TI  - Aortic valve insufficiency in the teenager and young adult: the role of
      prosthetic valve replacement.
AB  - The contents of this article were presented in the session "Aortic insufficiency
      in the teenager" at the congenital parallel symposium of the 2013 Society of
      Thoracic Surgeons (STS) annual meeting. The accompanying articles detail the
      approaches of aortic valve repair and the Ross procedure.(1,2) The current
      article focuses on prosthetic valve replacement. For many young patients
      requiring aortic valve surgery, either aortic valve repair or a Ross procedure
      provides a good option. The advantages include avoidance of anticoagulation and
      potential for growth. In other patients, a prosthetic valve is an appropriate
      alternative. This article discusses the current state of knowledge regarding
      mechanical and bioprosthetic valve prostheses and their specific advantages
      relative to valve repair or a Ross procedure. In current practice, young patients
      requiring aortic valve surgery frequently undergo valve replacement with a
      prosthetic valve. In STS adult cardiac database, among patients <=30 years of age
      undergoing aortic valve surgery, 34% had placement of a mechanical valve, 51% had
      placement of a bioprosthetic valve, 9% had aortic valve repair, and 2% had a Ross
      procedure. In the STS congenital database, among patients 12 to 30 years of age
      undergoing aortic valve surgery, 21% had placement of a mechanical valve, 18% had
      placement of a bioprosthetic valve, 30% had aortic valve repair, and 24% had a
      Ross procedure. In the future, the balance among these options may be altered by
      design improvements in prosthetic valves, alternatives to warfarin, the
      development of new patch materials for valve repair, and techniques to avoid Ross
      autograft failure. 

PMID- 24327635
TI  - The Ross operation in adolescents.
AB  - PURPOSE: The pulmonary autograft aortic valve replacement (Ross AVR) is the AVR
      of choice for children below the teenage years. Recent literature has questioned
      the durability of the Ross AVR in older children and young adults that present
      predominantly with aortic regurgitation and a dilated aortic root. At our center,
      the Ross AVR has been an excellent choice for most children and young and middle
      aged adults. The Ross AVR is an especially good choice in young females who plan
      on becoming pregnant. We reviewed our experience with the Ross AVR in older
      children and young adults (10-20 years old) and analyzed mortality, early and
      late complications, and the need for reoperation and compared it to non-Ross AVR
      patients of the same age group during the same time period. METHODS: Between 1993
      and 2013, 79 children and young adults, of which 19 were female, between the age
      of 10 and 20, mean of 16.0 +/- 2.7 years, underwent the Ross AVR. Follow-up
      ranged from 1 month to 20 years with a mean of 6.9 +/- 5.8 years. Patients with
      primary and/or predominant aortic regurgitation and a dilated aortic root and/or
      ascending aorta at any level were called the "primarily aortic insufficiency (AI)
      group" (PAIG); 38 (48%) met this criteria. Because we saw some pathologic root
      enlargement and/or progressive aortic regurgitation in our early Ross experience
      (1993-2000), we modified our technique and postoperative management in 2000; 51
      (65%) of 79 patients underwent the modified technique while 28 underwent our
      original Ross root replacement technique. The modified technique included
      reinforcing the aortic valve annulus and sinotubular junction and resecting or
      replacing the ascending aorta if it was dilated (>30 mm). Twenty-six patients
      during this same time period and in the same age group underwent the non-Ross AVR
      with a mean age of 16.5 +/- 2 years. Seven of these 26 non-Ross patients were
      female, and 16 (62%) presented with aortic regurgitation as their primary lesion.
      RESULTS: The early mortality for the Ross group and the non-Ross group was 0% and
      4%, respectively. Late mortality for the Ross group was 2.5% and 0% for the non
      Ross group. Of the 28 patients, 14 (50%) receiving the early Ross operation prior
      to 2000 have required reoperations. Only three (5.9%) of the 51 patients done
      after 2000 have required surgical reintervention (P <.01). In all, 11 (34%) of
      our Ross patients operated prior to 2000 and three (6%) after 2000 have required
      reintervention on their autografts. Patients in the PAIG had zero early and late
      deaths and a 16% rate of reoperation on the autograft compared to zero early and
      two late deaths and 20% rate of reoperation in patients not in the PAIG group (P
      = .266 and .467 respectively). The actuarial survival for the Ross group at 5 (N
      = 42), 10 (N = 24), and 20 (N = 1) years was 100%, 97%, and 73% respectively.
      Survival for the non-Ross group at 5 (N = 18), 10 (N = 8), and 20 (N = 1) years
      was 96%, 96%, and 96%, respectively; this difference in survival was not
      statistically significant (P =.90). Differences in survival without reoperation
      for both the groups were not statistically significant (P =.55). When comparing
      patients who had the newer Ross AVR technique and the non-Ross AVR patients,
      there was a significantly lower incidence of late aortic stenosis (AS) with a
      resting gradient greater than 20 mm Hg, 0% versus 53% (P <.001). CONCLUSION: The
      Ross AVR is the procedure of choice for adolescents requiring AVR who have a
      normal pulmonary valve. There was no difference between the outcomes in patients
      who were in the PAIG group compared to non-PAIG patients. There was no difference
      in survival without reoperation between the Ross AVR and the non-Ross AVR within
      the 10- to 20-year age group. The Ross AVR patients had lower incidences of
      nonoperative complications. The Ross AVR patients had excellent hemodynamic
      outcomes with a significantly lower incidence of late AS when compared to the non
      Ross AVR group. Reports of 15- to 20-year survival for the Ross AVR are
      encouraging. Long-term follow-up is necessary in all patients with aortic valve
      disease regardless of the treatment modality.

PMID- 24327636
TI  - Systematic approach to aortic valvuloplasty in children and young adults.
AB  - Valve repair in children and young adults is an attractive alternative to
      replacement or Ross procedure. In the past, the various valvuloplasty techniques
      have addressed isolated valve pathology. Recently, however, a holistic approach
      involving repair of all aortic root structures has evolved and promised to be an
      excellent alternative to valve replacement. It provides good long-term results
      and avoids all the drawback of prosthetic valve insertion in this age group.
      Development of ideal patch material needed for valve repair and better
      understanding of the anatomy and function of the aortic root may further improve
      the short- and long-term outcomes of aortic valvuloplasty. 

PMID- 24327637
TI  - Descending aortic and innominate artery cannulation for aortic arch repair with
      mildly hypothermic continuous cardiopulmonary bypass in infants and children.
AB  - A technique is described for exposure of the descending aorta, allowing separate
      arterial cannulation for perfusion of the upper and lower body during
      reconstruction of the aortic arch, maintaining continuous full-flow
      cardiopulmonary bypass to the entire body. This single technique is applicable to
      all aortic arch pathologies and allows an unhurried aortic reconstruction in an
      unobstructed field. 

PMID- 24327638
TI  - Native pulmonary valve restoration after remote tetralogy of fallot repair: how
      to do it.
AB  - Methods to repair tetralogy of Fallot have evolved from large ventriculotomy,
      large transannular patch placement techniques to smaller, transatrial approaches
      with valve-sparing strategies in select patients. Despite these advances, there
      continue to be patients in whom transannular patch is inevitable, and the
      management of the resulting pulmonary insufficiency that develops from this has
      been the source of considerable discussion. Techniques aimed at restoring
      pulmonary valve competence utilizing the remaining valve leaflets after
      transannular patch placement have recently been proposed for very select patient
      populations. We review the technical aspects of the operation including removal
      of the transannular patch and bicuspidization of a formerly tricuspid pulmonary
      valve, which results in a competent, nonstenotic valve. This report confirms the
      feasibility of these operative details and highlights the importance of planning
      before initial repair of tetralogy of Fallot as a way to prepare for a future
      valve restoration procedure and therefore avoid prosthetic valve placement. 

PMID- 24327639
TI  - Pulmonary artery aneurysm with patent arterial duct: resection of aneurysm and
      ductal division.
AB  - Congenital or acquired aneurysm of the pulmonary artery (PA) is rare. Although
      aneurysms are described following surgical treatment of patent ductus arteriosus
      (PDA), occurrence of this lesion in association with PDA without previous surgery
      is extremely uncommon. An eight-year-old patient with PDA and aneurysm of the
      main PA is described in this report. Clinical diagnosis of PDA was made upon
      presentation. Diagnosis of PA aneurysm was suspected on chest x-ray and was
      confirmed on transthoracic echocardiography. Successful surgical resection of the
      aneurysm and division of the duct were performed under cardiopulmonary bypass.
      The patient did well on follow-up both from clinical and echocardiographic point
      of view. 

PMID- 24327640
TI  - Lung decortication and lobectomy in a child with unrepaired tetralogy of fallot.
AB  - Patients with uncorrected tetralogy of Fallot (TOF) have been reported as
      undergoing emergency noncardiac surgeries such as cesarean section, brain abscess
      drainage, and major abdominal surgery. The uncorrected TOF group presents a great
      challenge with issues related to long-term effects of chronic hypoxemia and
      decreased pulmonary blood flow modifying patient physiology. We report a rare
      case of a child with uncorrected TOF with necrotizing streptococcal pneumonia
      complicated by empyema and bronchopleural fistula. The child successfully
      underwent lung decortication and right middle lobectomy in the first stage
      followed by an intracardiac repair (ICR) 15 days later. This staged approach was
      directed at controlling the infective focus, improving the pulmonary status, and
      following it up with a definitive ICR electively. 

PMID- 24327641
TI  - Surgical unroofing of an anomalous right coronary artery arising from the
      posterior left sinus of valsalva.
AB  - A 25-year-old male patient presented with sudden collapse due to a cardiac arrest
      during physical exercise. An electrocardiogram revealed ST-T wave abnormalities.
      A coronary catheterization and complementary computer tomography angiography
      showed an anomalous right coronary artery arising from the posterior left sinus
      of Valsalva. A successful surgical unroofing was performed. 

PMID- 24327642
TI  - Single-stage surgical correction of combination lesions through thoracotomy.
AB  - Coarctation of the descending aorta is associated with significant cardiac
      lesions in up to 50% of the patients. Under such circumstances, surgical
      management requires consideration of the nature of the associated lesion which
      usually requires a median sternotomy for surgical correction. Coarctation of the
      aorta (COA) is, therefore, rarely associated with lesions that are amenable to
      surgical correction through a thoracotomy incision. In this case report, we
      report a case of COA with significant associated cardiac disease that was
      repaired through a left thoracotomy incision. A 13-year-old boy was found to have
      COA and also partial anomalous pulmonary venous drainage of the left upper
      pulmonary vein to the innominate vein. Both the lesions were surgically corrected
      simultaneously through a thoracotomy. 

PMID- 24327643
TI  - Urgent hepatic to azygous vein connection for thrombosis of hepatic vein to
      pulmonary artery conduit.
AB  - We report on an emergent use of hepatic-to-azygous vein connection using a 10-mm
      polytetrafluoroethylene graft in a 6-year-old girl who developed acute thrombosis
      of an extracardiac graft conduit from the hepatic veins to the pulmonary
      arteries. She had left atrial isomerism, interrupted inferior vena cava with
      azygous continuation, and had undergone surgical creation of bilateral superior
      cavopulmonary connections 5 years earlier. The emergency procedure to create
      hepatic-to-azygous connection resulted in successful salvage of the patient who
      was subsequently able to maintain stable oxygen saturations and experienced rapid
      regression of hepatic congestion and pleural effusions. Six months following the
      procedure, oxygen saturation was above 90%. Repeated echocardiography and
      computed tomography angiography showed patency of the hepatic-to-azygous
      connection. 

PMID- 24327644
TI  - Thoracoscopic pericardiectomy for constrictive pericarditis in a pediatric
      patient with mulibrey nanism.
AB  - Mulibrey nanism is a rare autosomal recessive disease with multisystem
      involvement. Clinical deterioration is most often related to cardiac involvement
      in the form of restrictive or constrictive disorders, and pericardiectomy may be
      required. We report a case of Mulibrey nanism in a patient of non-Finnish origin,
      where a thoracoscopic pericardiectomy helped in good palliation and clinical
      recovery. 

PMID- 24327645
TI  - Late bidirectional glenn anastomosis in a 54-year-old patient with unoperated
      functionally univentricular heart.
AB  - We report the case of a 54-year-old patient with complex univentricular
      physiology who presented with worsening exercise intolerance, chronic cyanosis,
      and uncontrolled heart failure. Investigations included echocardiography, cardiac
      magnetic resonance imaging, and cardiac catheterization. After discussion in a
      multidisciplinary meeting, the patient underwent successful surgery that included
      a bidirectional Glenn anastomosis and repair of the atrioventricular (AV)
      junction. She recovered well and on follow-up had substantially less cyanosis and
      heart failure. We demonstrated that common AV valve repair and Glenn shunt can be
      used together successfully in appropriately selected older patients as palliation
      for complex congenital heart disease with functionally univentricular physiology.

PMID- 24327646
TI  - Use of beta-blockade and levosimendan for separation from extracorporeal life
      support in an infant with postoperative diastolic dysfunction.
AB  - Diastolic dysfunction is common in infants and neonates with left ventricular
      (LV) outflow tract obstruction and may lead to low-cardiac output in the
      postoperative period. We present a management strategy for severe postrepair
      diastolic dysfunction in an infant with critical congenital aortic stenosis and
      LV hypertrophy, employing beta-blockade and levosimendan. 

PMID- 24327647
TI  - Secondary repair of Ebstein's anomaly with atrioventricular septal defect using
      the cone technique.
AB  - A nine-year-old boy with incomplete atrioventricular septal defect (AVSD) and
      Ebstein's anomaly had undergone a closure of primum atrial septal defect and
      repair of right and left AV valves at four years of age. He presented with severe
      regurgitation of the right AV valve. He underwent further surgery, and a cone
      reconstruction of the right AV valve was performed. The association of Ebstein's
      anomaly with AVSD has been reported only rarely. We present a case of this
      association treated with the previously unreported application of the cone
      reconstruction (da Silva repair) as a secondary strategy. 

PMID- 24327648
TI  - Cervical arch with aortic kinking.

PMID- 24327651
TI  - Anatomically corrected malposition and double outlet ventricle.

PMID- 24327652
TI  - Anatomically corrected malposition.

PMID- 24327653
TI  - Isolated resistant ascites in a patient with hypoxemic congenital heart disease.

PMID- 24327654
TI  - Isolated left common carotid artery arising from the main pulmonary artery: where
      is the ductus arteriosus? an embryologist's view.

PMID- 24327655
TI  - Lack of association between venous hemodynamics, venous morphology and the
      postthrombotic syndrome after upper extremity deep venous thrombosis.
AB  - OBJECTIVES: To explore the association of the postthrombotic syndrome with venous
      hemodynamics and morphological abnormalities after upper extremity deep venous
      thrombosis. METHODS: Thirty-seven patients with a history of upper extremity deep
      venous thrombosis treated with anticoagulation alone underwent a single study
      visit (mean time after diagnosis: 44.4 +/- 28.1 months). Presence and severity
      postthrombotic syndrome were classified according to the modified Villalta score.
      Venous volume and venous emptying were determined by strain-gauge
      plethysmography. The arm veins were assessed for postthrombotic abnormalities by
      ultrasonography. The relationship between postthrombotic syndrome and hemodynamic
      and morphological sequelae was evaluated using univariate significance tests and
      Spearman's correlation analysis. RESULTS: Fifteen of 37 patients (40.5%)
      developed postthrombotic syndrome. Venous volume and venous emptying of the arm
      affected by upper extremity deep venous thrombosis did not correlate with the
      Villalta score (rho = 0.17 and 0.19; p = 0.31 and 0.25, respectively). Residual
      morphological abnormalities, as assessed by ultrasonography, did not differ
      significantly between patients with and without postthrombotic syndrome (77.3%
      vs. 86.7%, p = 0.68). CONCLUSIONS: Postthrombotic syndrome after upper extremity
      deep venous thrombosis is not associated with venous hemodynamics or residual
      morphological abnormalities.

PMID- 24327656
TI  - The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding
      the tetratricopeptide repeat (TPR) domain.
AB  - Protein phosphatase 5 (PP5) is auto-inhibited by intramolecular interactions with
      its tetratricopeptide repeat (TPR) domain. Hsp90 has been shown to bind PP5 to
      activate its phosphatase activity. However, the functional implications of
      binding Hsp70 to PP5 are not yet clear. In this study, we find that both Hsp90
      and Hsp70 bind to PP5 using a luciferase fragment complementation assay. A
      fluorescence polarization assay shows that Hsp90 (MEEVD motif) binds to the TPR
      domain of PP5 almost 3-fold higher affinity than Hsp70 (IEEVD motif). However,
      Hsp70 binding to PP5 stimulates higher phosphatase activity of PP5 than the
      binding of Hsp90. We find that PP5 forms a stable 1:1 complex with Hsp70, but the
      interaction appears asymmetric with Hsp90, with one PP5 binding the dimer.
      Solution NMR studies reveal that Hsc70 and PP5 proteins are dynamically
      independent in complex, tethered by a disordered region that connects the Hsc70
      core and the IEEVD-TPR contact area. This tethered binding is expected to allow
      PP5 to carry out multi-site dephosphorylation of Hsp70-bound clients with a range
      of sizes and shapes. Together, these results demonstrate that Hsp70 recruits PP5
      and activates its phosphatase activity which suggests dual roles for PP5 that
      might link chaperone systems with signaling pathways in cancer and development. 

PMID- 24327657
TI  - The D-ring, not the A-ring, rotates in Synechococcus OS-B' phytochrome.
AB  - Phytochrome photoreceptors in plants and microorganisms switch photochromically
      between two states, controlling numerous important biological processes. Although
      this phototransformation is generally considered to involve rotation of ring D of
      the tetrapyrrole chromophore, Ulijasz et al. (Ulijasz, A. T., Cornilescu, G.,
      Cornilescu, C. C., Zhang, J., Rivera, M., Markley, J. L., and Vierstra, R. D.
      (2010) Nature 463, 250-254) proposed that the A-ring rotates instead. Here, we
      apply magic angle spinning NMR to the two parent states following studies of the
      23-kDa GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domain fragment of
      phytochrome from Synechococcus OS-B'. Major changes occur at the A-ring covalent
      linkage to the protein as well as at the protein residue contact of ring D.
      Conserved contacts associated with the A-ring nitrogen rule out an A-ring
      photoflip, whereas loss of contact of the D-ring nitrogen to the protein implies
      movement of ring D. Although none of the methine bridges showed a chemical shift
      change comparable with those characteristic of the D-ring photoflip in canonical
      phytochromes, denaturation experiments showed conclusively that the same occurs
      in Synechococcus OS-B' phytochrome upon photoconversion. The results are
      consistent with the D-ring being strongly tilted in both states and the C15=C16
      double bond undergoing a Z/E isomerization upon light absorption. More subtle
      changes are associated with the A-ring linkage to the protein. Our findings thus
      disprove A-ring rotation and are discussed in relation to the position of the D
      ring, photoisomerization, and photochromicity in the phytochrome family. 

PMID- 24327658
TI  - Casein kinase 1 regulates sterol regulatory element-binding protein (SREBP) to
      control sterol homeostasis.
AB  - Sterol homeostasis is tightly controlled by the sterol regulatory element-binding
      protein (SREBP) transcription factor that is highly conserved from fungi to
      mammals. In fission yeast, SREBP functions in an oxygen-sensing pathway to
      promote adaptation to decreased oxygen supply that limits oxygen-dependent sterol
      synthesis. Low oxygen stimulates proteolytic cleavage of the SREBP homolog Sre1,
      generating the active transcription factor Sre1N that drives expression of sterol
      biosynthetic enzymes. In addition, low oxygen increases the stability and DNA
      binding activity of Sre1N. To identify additional signals controlling Sre1
      activity, we conducted a genetic overexpression screen. Here, we describe our
      isolation and characterization of the casein kinase 1 family member Hhp2 as a
      novel regulator of Sre1N. Deletion of Hhp2 increases Sre1N protein stability and
      ergosterol levels in the presence of oxygen. Hhp2-dependent Sre1N degradation by
      the proteasome requires Hhp2 kinase activity, and Hhp2 binds and phosphorylates
      Sre1N at specific residues. Our results describe a role for casein kinase 1 as a
      direct regulator of sterol homeostasis. Given the role of mammalian Hhp2
      homologs, casein kinase 1delta and 1epsilon, in regulation of the circadian
      clock, these findings may provide a mechanism for coordinating circadian rhythm
      and lipid metabolism. 

PMID- 24327660
TI  - A survey of prognosis discussions held by health-care providers who request
      palliative care consultation.
AB  - BACKGROUND: Patient misunderstandings about prognosis may be related to lack of
      communication. AIM: This study aimed to examine prognosis discussions held with
      hospitalized patients for whom palliative care consultations were requested, and
      if prognosis discussions did not occur, to explore why not. DESIGN: This was a
      survey conducted over the telephone from a convenience sample of health-care
      providers who requested palliative care consultations. Respondents were asked
      about whether prognosis had been discussed with the patient and the topics
      addressed. PARTICIPANTS: A total of 65 health-care providers who called to
      request a consultation from the palliative care team in a large academic medical
      center in the United States. RESULTS: Of the 65 responses, 45 (69.2%) subjects
      reported that a prognosis discussion had occurred, while 15 (23.1%) reported that
      a prognosis discussion had not taken place. Among the surveys reporting a
      prognosis discussion, a majority of providers responded that most aspects of
      prognosis were discussed, with the exceptions of life expectancy, survival
      rates/statistics, and psychosocial concerns. When the prognosis discussion had
      not occurred, the most common reasons for omitting the prognosis discussion
      included difficulty in determining prognosis, the perception that the patient
      already knew his or her prognosis, and the belief that the prognosis discussion
      was better suited for a different specialty. CONCLUSIONS: The results of this
      study highlight the uncertainty that primary team providers in the academic
      hospital environment have with prognostication, which is a complex process for
      which this set of providers, composed primarily of medical trainees and nurses,
      may not have had sufficient training.

PMID- 24327659
TI  - The large Hsp70 Grp170 binds to unfolded protein substrates in vivo with a
      regulation distinct from conventional Hsp70s.
AB  - The Hsp70 superfamily is a ubiquitous chaperone class that includes conventional
      and large Hsp70s. BiP is the only conventional Hsp70 in the endoplasmic reticulum
      (ER) whose functions include: assisting protein folding, targeting misfolded
      proteins for degradation, and regulating the transducers of the unfolded protein
      response. The ER also possesses a single large Hsp70, the glucose-regulated
      protein of 170 kDa (Grp170). Like BiP it is an essential protein, but its
      cellular functions are not well understood. Here we show that Grp170 can bind
      directly to a variety of incompletely folded protein substrates in the ER, and as
      expected for a bona fide chaperone, it does not interact with folded secretory
      proteins. Our data demonstrate that Grp170 and BiP associate with similar
      molecular forms of two substrate proteins, but while BiP is released from
      unfolded substrates in the presence of ATP, Grp170 remains bound. In comparison
      to conventional Hsp70s, the large Hsp70s possess two unique structural features:
      an extended C-terminal alpha-helical domain and an unstructured loop in the
      putative substrate binding domain with an unknown function. We find that in the
      absence of the alpha-helical domain the interaction of Grp170 with substrates is
      reduced. In striking contrast, deletion of the unstructured loop results in
      increased binding to substrates, suggesting the presence of unique intramolecular
      mechanisms of control for the chaperone functions of large Hsp70s. 

PMID- 24327661
TI  - The association of serum antiphospholipid antibodies and dilute Russell's viper
      venom times.
AB  - AIMS: We hypothesised that there is a threshold value for the association of
      dilute Russell's viper venom times (dRVVT) with positive immunoglobin G
      antiphospholipid antibody (IgG-APLA) test results. METHODS: We tested 120
      controls and a cohort of 2412 outpatients who had concomitant test results for
      dRVVT and IgG-APLA (IgG antibodies to cardiolipins and beta2-glycoprotein I). We
      also selected a subgroup who had repeated IgG-APLA tests at least 12 weeks apart
      (1398 patients with multiple beta2-glycoprotein I tests and 672 with multiple aCL
      tests). We cross tabulated the proportion of IgG-APLA single positive, double
      positive and persistently positive antibodies with dRVVT values. RESULTS: The
      distribution of the dRVVT results from the reference population was consistent
      with an upper limit of the reference interval of 1.22 to >1.48. A consistent
      increase in the proportion of IgG-APLA single, double positive and persistently
      positive antibody tests occurred in the group with a normalised dRVVT ratio of
      1.40-1.49. IgG-APLA double positivity was found in 12.5% (4 of 32) patients with
      a ratio of dRVVT 1.40-1.49 compared with 3.3% (6/181) of those with a ratio of
      dRVVT 1.20-1.39 (p=0.045). CONCLUSIONS: We conclude that there is an association
      between dRVVT positivity and elevated proportions of single, double and
      persistently positive IgG-APLA test results with an apparent threshold effect.
      These findings may provide a general guide to risk and suggest a way to choose
      from a wide range of possible upper limits of the reference interval.

PMID- 24327662
TI  - Bone marrow trephine biopsy involvement by lymphoma: review of histopathological
      features in 511 specimens and correlation with diagnostic biopsy, aspirate and
      peripheral blood findings.
AB  - AIMS: This study aimed to evaluate the key features of bone marrow trephine (BMT)
      biopsy involvement by lymphoma. METHODS: 511 cases were assessed for percentage
      of marrow involvement, pattern of involvement (diffuse, nodular, paratrabecular,
      interstitial or intrasinusoidal), presence/absence of granulomas, stromal
      fibrosis and necrosis, presence/absence of neoplastic/reactive follicles and
      discordance with other biopsy sites. Correlation with aspirate and peripheral
      blood findings was made in a subset of 345 patients (167 aspirates, 178 blood).
      RESULTS: The most frequent subtype was follicular lymphoma (26.2%) followed by
      extranodal marginal zone (23.1%), lymphoplasmacytic (19.2%), diffuse large B cell
      (DLBCL) (12.5%), Hodgkin (HL) (5.7%) and mantle cell lymphomas (4.3%). The
      predominant pattern in follicular lymphoma was paratrabecular. Marginal zone
      lymphomas of all types and lymphoplasmacytic lymphoma showed a relatively even
      distribution between diffuse, interstitial, paratrabecular and nodular patterns.
      The majority of mantle cell lymphoma cases showed either diffuse or nodular
      patterns. A diffuse pattern was common in DLBCL and Burkitt lymphomas. An
      intrasinusoidal pattern was seen only in extranodal and splenic marginal zone
      lymphomas. Granulomas and fibrosis were uncommon in small cell B cell lymphomas
      but frequent in DLBCL and HL. Aspirate and trephine results concurred in 73.8% of
      cases overall, but this varied widely between subtypes. Peripheral blood
      involvement rates by lymphoma also varied, with a mean of 37.1%. CONCLUSIONS:
      Different lymphomas often demonstrate reliably characteristic architectural
      patterns of marrow involvement which can help differentiate them even when
      cytological features do not permit this, and marrow stromal and other background
      changes may also be useful pointers towards a particular lymphoma subtype.

PMID- 24327663
TI  - Theory and the fallacy of misplaced concreteness.

PMID- 24327664
TI  - No-show to primary care appointments: why patients do not come.
AB  - BACKGROUND: Missed primary care appointments lead to poor disease control and
      later presentation to care. No-show rates are higher in clinics caring for
      underserved populations and may contribute to poorer health outcomes in this
      group. The objective of this study was to determine who were the patients not
      showing to primary care appointments and their reasons to no-show. METHODS: A
      retrospective study was conducted at a community health center serving a
      predominantly Latino, immigrant, low-income population. Adult patients >18 years
      old who did not show to primary care appointments during a 5-month period were
      called by a bilingual (English and Spanish) patient service coordinator. The
      patients' reported reason for missing the appointment was documented. Two-sided t
      test of proportions was used to compare demographic characteristics of the
      patients that showed to their appointments to patients that did not. RESULTS: Of
      7508 scheduled appointments, 5604 were included in the analysis and 927 (16.5%)
      no-showed. There were 735 (79%) calls made to the patients who missed their
      appointments and 273 (37%) were reached. The 2 most common reasons for missing an
      appointment were forgetting (n = 97, 35.5%) and miscommunication (n = 86, 31.5%).
      When compared with patients who came to their appointments, patients who no
      showed were younger (P < .0001), more likely to be black (P = .0423) or Hispanic
      (P = .0001), and to have Medicaid (P < .0001). CONCLUSIONS: No-show rates
      interfere with quality primary care. Interventions designed to target reasons for
      no-show are needed to help reduce the no-show rate, improve access and decrease
      health disparities in underserved patient populations.

PMID- 24327665
TI  - Using electronic medical record data to characterize the level of medication use
      by age-groups in a network of primary care clinics.
AB  - PURPOSE: Our primary aim was to characterize the level of medication use across
      age-groups by examining electronic medical record data for a large number of
      patients receiving care in primary care clinics. A secondary aim was to identify
      factors associated with higher levels of medication use or polypharmacy. METHODS:
      We conducted a retrospective query of electronic medical record data from a
      clinical data warehouse, evaluating 114 012 patients seen in primary care clinics
      at least once in the previous 6 months. Medication use was evaluated in 3
      different categories: level 1 (0-4 medications), level 2 (5-9 medications), and
      level 3 (>= 10 medications). Multivariate analysis was used to analyze different
      patient demographics and comorbidities for association with level of medication
      use. RESULTS: At ages 18 to 24 years, 15% (male) to 23% (female) of patients were
      taking greater than 5 medications, a trend that continued to increase with older
      cohorts. Female patients were more likely to have level 2 (odds ratio [OR] =
      1.76) and level 3 (OR = 2.73) use compared with men. Level 2 and level 3 use was
      associated with other patient characteristics, including number of patient
      encounters (level 2 OR = 2.99; level 3 OR = 8.08 for >7 encounters) and common
      chronic conditions such as chronic pain (level 2 OR = 2.56; level 3 OR = 6.40),
      diabetes (level 2 OR = 2.4; level 3 OR = 4.61), heart disease (level 2 OR = 1.99;
      level 3 OR = 3.65), hypertension (level 2 OR = 2.27; level 3 OR = 2.87), and
      dyslipidemia (level 2 OR = 1.82; level 3 OR = 2.12). CONCLUSION: Electronic
      medical record data may be an important tool for providing more comprehensive
      information regarding medication usage. Medication usage assessed by electronic
      medical records, even among the youngest cohort, appears to be greater than other
      sources of medication usage indicate. Higher levels of medication use were
      associated with a number of factors, including gender, body mass index, number of
      patient encounters, and comorbid conditions.

PMID- 24327666
TI  - Satisfaction with cosmesis and priorities for cosmesis design reported by lower
      limb amputees in the United Kingdom: instrument development and results.
AB  - BACKGROUND: Amputee satisfaction with cosmesis and the importance they place on
      cosmesis design have not been published in the literature. OBJECTIVES: To
      investigate the current satisfaction levels of amputees in the United Kingdom
      with their cosmesis and the importance placed on attributes of cosmesis design to
      inform future cosmesis redesign. STUDY DESIGN: Cross-sectional questionnaire
      study. METHODS: Questionnaires were administered to lower limb amputees in the
      United Kingdom. Satisfaction scores and the overall importance ranking of
      cosmesis features were calculated. Statistically significant relationships
      between two demographic, satisfaction or importance variables were tested using
      Fisher's exact tests (one-tailed) at a significance level p = 0.05. RESULTS:
      Between 49% and 64% of respondents reported neutral or dissatisfied opinions with
      the cosmesis features (greater than 50% for five of the nine features). The three
      most important features identified were shape matching the cosmesis to the sound
      limb, free prosthetic joint movement underneath the cosmesis and natural fit of
      clothing over the cosmesis. CONCLUSIONS: The results indicate that current
      cosmesis satisfaction levels of amputees in the United Kingdom are below what the
      medical device industry and clinical community would desire. The most important
      cosmesis features identified by the sample can be used to direct future cosmesis
      design research. CLINICAL RELEVANCE: The findings will enable the medical device
      industry to improve cosmesis design in the areas that are important to amputees.
      The findings also counter anecdotal opinions held by clinicians, providing an
      opportunity for them to evaluate any preconceptions they harbour and how this
      might influence their clinical work.

PMID- 24327667
TI  - Oculo-facial rehabilitation after facial cancer removal: updated CAD/CAM
      procedures: a pilot study.
AB  - BACKGROUND AND AIM: Leaving open or closing the oculo-facial defect by means of a
      myocutaneous flap mainly depends on maxillofacial surgical considerations. For
      those cases that present a closed defect, the authors aim to evaluate an
      innovative method of ocular bulb positioning using a magnetic resonance imaging
      dataset. TECHNIQUE: Following cancer removal and plastic reconstructive surgery,
      a Digital Imaging and Communications in Medicine format magnetic resonance
      imaging dataset was used to determine the volume and position of the left ocular
      bulb. The exact location of the prosthetic bulb was determined by mirroring this
      position on the affected side. Images of the eyeglasses were imported into the
      virtual environment, and the designs of the substructure and facial prosthesis
      were projected using computer-aided design/computer-aided manufacture (CAD/CAM)
      technology. DISCUSSION: The updated method presented here enables restoration
      with a facial prosthesis, even when a myocutaneous flap is used to close the
      defect, thereby resolving the problem of ocular bulb positioning and enabling the
      rapid and easy design of a retention system connected to eyeglasses. CLINICAL
      RELEVANCE: The proposed protocol aims to develop and describe a viable method for
      the construction of a facial prosthesis for a patient whose face had been
      reconstructed using a myocutaneous free flap.

PMID- 24327668
TI  - Effect of an ankle-foot orthosis on knee joint mechanics: a novel conservative
      treatment for knee osteoarthritis.
AB  - BACKGROUND: Several conservative treatments for medial knee osteoarthritis such
      as knee orthosis and laterally wedged insoles have been shown to reduce the load
      in the medial knee compartment. However, those treatments also present
      limitations such as patient compliance and inconsistent results regarding the
      treatment success. OBJECTIVE: To analyze the effect of an ankle-foot orthosis on
      the knee adduction moment and knee joint alignment in the frontal plane in
      subjects with knee varus alignment. STUDY DESIGN: Controlled laboratory study,
      repeated measurements. METHODS: In total, 14 healthy subjects with knee varus
      alignment were analyzed in five different conditions: without orthotic, with
      laterally wedged insoles, and with an ankle-foot orthosis in three different
      adjustments. Three-dimensional kinetic and kinematic data were collected during
      gait analysis. RESULTS: Significant decreases in knee adduction moment, knee
      lever arm, and joint alignment in the frontal plane were observed with the ankle
      foot orthosis in all three different adjustments. No significant differences
      could be found in any parameter while using the laterally wedged insoles.
      CONCLUSION: The ankle-foot orthosis was effective in reducing the knee adduction
      moment. The decreases in this parameter seem to be achieved by changing the knee
      joint alignment and thereby reducing the knee lever arm in the frontal plane.
      CLINICAL RELEVANCE: This study presents a novel approach for reducing the load in
      the medial knee compartment, which could be developed as a new treatment option
      for patients with medial knee osteoarthritis.

PMID- 24327669
TI  - Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer from the
      American Society of Clinical Oncology.
AB  - A MESSAGE FROM ASCO'S PRESIDENT: Since its founding in 1964, the American Society
      of Clinical Oncology (ASCO) has been committed to improving cancer outcomes
      through research and the delivery of quality care. Research is the bedrock of
      discovering better treatments--providing hope to the millions of individuals who
      face a cancer diagnosis each year. The studies featured in "Clinical Cancer
      Advances 2013: Annual Report on Progress Against Cancer From the American Society
      of Clinical Oncology" represent the invaluable contributions of thousands of
      patients who participate in clinical trials and the scientists who conduct basic
      and clinical research. The insights described in this report, such as how cancers
      hide from the immune system and why cancers may become resistant to targeted
      drugs, enable us to envision a future in which cancer will be even more
      controllable and preventable. The scientific process is thoughtful, deliberate,
      and sometimes slow, but each advance, while helping patients, now also points
      toward new research questions and unexplored opportunities. Both dramatic and
      subtle breakthroughs occur so that progress against cancer typically builds over
      many years. Success requires vision, persistence, and a long-term commitment to
      supporting cancer research and training. Our nation's longstanding investment in
      federally funded cancer research has contributed significantly to a growing array
      of effective new treatments and a much deeper understanding of the drivers of
      cancer. But despite this progress, our position as a world leader in advancing
      medical knowledge and our ability to attract the most promising and talented
      investigators are now threatened by an acute problem: Federal funding for cancer
      research has steadily eroded over the past decade, and only 15% of the ever
      shrinking budget is actually spent on clinical trials. This dismal reality
      threatens the pace of progress against cancer and undermines our ability to
      address the continuing needs of our patients. Despite this extremely challenging
      economic environment, we continue to make progress. Maintaining and accelerating
      that progress require that we keep our eyes on the future and pursue a path that
      builds on the stunning successes of the past. We must continue to show our
      policymakers the successes in cancer survival and quality of life (QOL) they have
      enabled, emphasizing the need to sustain our national investment in the
      remarkably productive US cancer research enterprise. We must also look to
      innovative methods for transforming how we care for-and learn from-patients with
      cancer. Consider, for example, that fewer than 5% of adult patients with cancer
      currently participate in clinical trials. What if we were able to draw lessons
      from the other 95%? This possibility led ASCO this year to launch CancerLinQ, a
      groundbreaking health information technology initiative that will provide
      physicians with access to vast quantities of clinical data about real-world
      patients and help achieve higher quality, higher value cancer care. As you read
      the following pages, I hope our collective progress against cancer over the past
      year inspires you. More importantly, I hope the pride you feel motivates you to
      help us accelerate the pace of scientific advancement. Clifford A. Hudis, MD,
      FACP President American Society of Clinical Oncology.

PMID- 24327670
TI  - Underestimating our influence over others' unethical behavior and decisions.
AB  - We examined the psychology of "instigators," people who surround an unethical act
      and influence the wrongdoer (the "actor") without directly committing the act
      themselves. In four studies, we found that instigators of unethical acts
      underestimated their influence over actors. In Studies 1 and 2, university
      students enlisted other students to commit a "white lie" (Study 1) or commit a
      small act of vandalism (Study 2) after making predictions about how easy it would
      be to get their fellow students to do so. In Studies 3 and 4, online samples of
      participants responded to hypothetical vignettes, for example, about buying
      children alcohol and taking office supplies home for personal use. In all four
      studies, instigators failed to recognize the social pressure they levied on
      actors through simple unethical suggestions, that is, the discomfort actors would
      experience by making a decision that was inconsistent with the instigator's
      suggestion. 

PMID- 24327672
TI  - Communicating through humour: A project of stand-up comedy about science.
AB  - A study of a project on science stand-up comedy developed in Portugal between
      2009 and 2013 is presented, in which thirteen scientists, coordinated by a
      science communicator and a professional actor, created and presented comedy acts.
      Eleven of these scientists were asked about their motivations to participate, the
      process of performance development and the perceived value of the project.
      Personal motivations were highly important, but professional reasons were also
      mentioned. Working in a group with the guidance of coordinators, testing and re
      writing the texts and gradually gaining confidence on stage were considered
      fundamental in the development of the shows. Additionally, a questionnaire
      revealed that the audience, most of whom were young adults, and held a higher
      education degree, were satisfied with the show. Overall, both participating
      scientists and audience members considered that stand-up comedy has potential for
      science communication. 

PMID- 24327671
TI  - Mental health selection and income support dynamics: multiple spell discrete-time
      survival analyses of welfare receipt.
AB  - BACKGROUND: The higher occurrence of common psychiatric disorders among welfare
      recipients has been attributed to health selection, social causation and
      underlying vulnerability. The aims of this study were to test for the selection
      effects of mental health problems on entry and re-entry to working-age welfare
      payments in respect to single parenthood, unemployment and disability. METHODS:
      Nationally representative longitudinal data were drawn from the Household Income
      and Labour Dynamics in Australia survey. Multiple spell discrete-time survival
      analyses were conducted using multinomial logistic regression models to test if
      pre-existing mental health problems predicted transitions to welfare. Analyses
      were stratified by sex and multivariate adjusted for mental health problems,
      father's occupation, socioeconomic position, marital status, employment history,
      smoking status and alcohol consumption, physical function and financial hardship.
      All covariates were modelled as either lagged effects or when a respondent was
      first observed to be at risk of income support. RESULTS: Mental health problems
      were associated with increased risk of entry and re-entry to disability,
      unemployment and single parenting payments for women, and disability and
      unemployment payments for men. These associations were attenuated but remained
      significant after adjusting for contemporaneous risk factors. CONCLUSIONS:
      Although we do not control for reciprocal causation, our findings are consistent
      with a health selection hypothesis and indicate that mental illness may be a
      contributing factor to later receipt of different types of welfare payments. We
      argue that mental health warrants consideration in the design and targeting of
      social and economic policies.

PMID- 24327673
TI  - Persistence of socioeconomic differences in adolescents' environmental tobacco
      smoke exposure in Finland: 1991-2009.
AB  - AIMS: Socioeconomic differences in children's exposure to environmental tobacco
      smoke (ETS) in favour of those with higher positions are known, but research is
      scarce on whether differences have persisted when smoking restrictions have been
      tightened. We examined socioeconomic differences in adolescents' ETS exposure
      from 1991 to 2009 in Finland where the tobacco law has gradually restricted
      smoking of population. METHODS: National cross-sectional surveys (1991-2009) in
      12-18-year-olds (N=72,726, response rate 77-56%). An outcome measure was self
      reported exposure to ETS (>= 1 hour/day). Parents' socioeconomic and adolescent's
      individual social position (school performance/career) were used as independent
      variables. Across four time periods, associations were studied by logistic
      regression. RESULTS: Over the study period 1991-2009, the proportion of
      adolescents exposed to ETS decreased from 17% to 6% (p <= 0.001). There were
      large and persistent differences between socioeconomic and parents' smoking
      groups. The decrease occurred in all groups but was smaller among 16-18-year-olds
      whose father had a low education. A steeper decline occurred among 16-18-year
      olds who were not in school or were in vocational school with poor school
      performance compared with those with more advanced educational career. Compared
      with other subgroups, the decline in ETS exposure was greater among those whose
      parents were smokers. CONCLUSIONS: Adolescents' ETS exposure remarkably decreased
      over time, when tobacco control measures were tightened, particularly among
      children of smoking parents. Socioeconomic differences persisted although
      diminishing differences were observed between educational groups at age 16-18.

PMID- 24327676
TI  - Pan-Cancer Initiative finds patterns of drivers.

PMID- 24327677
TI  - Targeting gaps in pediatric cancer science.

PMID- 24327678
TI  - Consortium launches genotyping effort.

PMID- 24327680
TI  - NIH-FDA effort focuses on tobacco research.

PMID- 24327681
TI  - Q&A: Elizabeth Blackburn on telomerase and tumors.

PMID- 24327682
TI  - A role for aspirin in cancer prevention?

PMID- 24327693
TI  - Dynamic interplay of oncogenes and T cells induces PD-L1 in the tumor
      microenvironment.
AB  - Tumor-infiltrating T cells have recently been found to upregulate
      immunosuppressive pathways, such as programmed cell death protein 1 ligand 1 (PD
      L1), in a paracrine fashion on tumor cells, but tumor cell-intrinsic regulation
      of PD-L1 is another potential mechanism. In this issue of Cancer Discovery, Akbay
      and colleagues show that signaling via mutant EGF receptor (EGFR) in murine lung
      tumor cells directly upregulates tumor PD-L1 and that therapeutic blockade of
      this pathway improves survival in EGFR-driven preclinical models-highlighting the
      dynamic interplay and therapeutic opportunities of cancer cell biology and immune
      biology.

PMID- 24327694
TI  - Teaching an old dog new tricks: drug repositioning in small cell lung cancer.
AB  - Jahchan and colleagues report the use of a biostatistical analysis to identify
      effective therapeutics for small cell lung cancer (SCLC). Their results reveal a
      new use for the tricyclic antidepressant imipramine in SCLC and shed light on the
      therapeutic potential of drug repositioning in cancer and other diseases.

PMID- 24327695
TI  - Personalized therapy for acute myeloid leukemia.
AB  - Patient-specific ex vivo drug sensitivity and resistance screening can identify
      rational drug candidates for the testing of personalized targeted therapy. An
      iterative approach of genomic and drug susceptibility characterization at
      sequential time points during clinical trials of targeted therapy in acute
      myeloid leukemia may be useful both for characterizing mechanisms of resistance
      and clonal evolution and also for identification of novel therapeutic targets and
      drug combinations.

PMID- 24327696
TI  - A systems biology approach to personalizing therapeutic combinations.
AB  - The identification of evidence-based, efficacious drug combinations for each
      cancer, among thousands of potential permutations, is a daunting task. In this
      perspective, we propose a systematic approach to defining such combinations by
      molecularly benchmarking a drug against a desired state of efficacy using model
      systems.

PMID- 24327698
TI  - Antibody-drug conjugate may inhibit pancreatic cancer.

PMID- 24327709
TI  - Tripling up for early-stage drug development.

PMID- 24327712
TI  - Nanopharmaceutical may offer benefits in combinations.

PMID- 24327713
TI  - Ramucirumab takes steps forward in gastric cancer.

PMID- 24327714
TI  - T-DM1 aids patients with advanced breast cancer.

PMID- 24327715
TI  - Drug firms chip in for multiple myeloma database.

PMID- 24327716
TI  - Decade-long survival possible after ipilimumab.

PMID- 24327717
TI  - Checkpoint inhibitor shows promise in smokers.

PMID- 24327718
TI  - Targeting resistance in lung cancer.

PMID- 24327719
TI  - The eminent and forgotten Roger Barone (c. 13th century): a great and innovative
      surgeon in Montpellier.

PMID- 24327720
TI  - Impact of vitamin D supplementation on inflammatory markers in African Americans:
      results of a four-arm, randomized, placebo-controlled trial.
AB  - African Americans have a disproportionate burden of inflammation-associated
      chronic diseases such as cancer and lower circulating levels of 25-hydroxyvitamin
      D [25(OH)D]. The effect of vitamin D3 (cholecalciferol) supplementation on
      inflammatory markers is uncertain. We conducted a randomized, double-blind,
      placebo-controlled trial of supplemental oral vitamin D (placebo, 1,000, 2,000,
      or 4,000 IU/day of vitamin D3 orally for 3 months) in 328 African Americans
      (median age, 51 years) of public housing communities in Boston, MA, who were
      enrolled over three consecutive winter periods (2007-2010). Change from 0 to 3
      months of plasma levels of 25(OH)D, high-sensitivity C-reactive protein (CRP),
      interleukin (IL)-6, IL-10, and soluble TNF-alpha receptor type 2 (sTNF-R2) in 292
      (89%) participants were measured. Overall, no statistically significant changes
      in CRP, IL-6, IL-10, and sTNF-R2 were observed after the vitamin D
      supplementation period. Baseline CRP was significantly inversely associated with
      the baseline 25(OH)D level (P < 0.001) in unadjusted and adjusted models. An
      interaction between baseline 25(OH)D and vitamin D supplementation was observed
      for outcome change in log CRP (month 3-month 0; P for interaction = 0.04). Within
      an unselected population of African Americans, short-term exposure to vitamin D
      supplementation produced no change in circulating inflammatory markers. This
      study confirms the strong independent association of CRP with 25(OH)D status even
      after adjusting for body mass index. Future studies of longer supplemental
      vitamin D3 duration are necessary to examine the complex influence of vitamin D3
      on CRP and other chronic inflammatory cytokines for possible reduction of cancer
      health disparities in African Americans.

PMID- 24327721
TI  - Naproxen induces cell-cycle arrest and apoptosis in human urinary bladder cancer
      cell lines and chemically induced cancers by targeting PI3K.
AB  - Naproxen [(S)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid] is a potent
      nonsteroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 and is
      widely used as an over-the-counter medication. Naproxen exhibits analgesic,
      antipyretic, and anti-inflammatory activities. Naproxen, as well as other
      nonsteroidal anti-inflammatory drug, has been reported to be effective in the
      prevention of urinary bladder cancer in rodents. However, potential targets other
      than the COX isozymes have not been reported. We examined potential additional
      targets in urinary bladder cancer cells and in rat bladder cancers. Computer
      kinase profiling results suggested that phosphoinositide 3-kinase (PI3K) is a
      potential target for naproxen. In vitro kinase assay data revealed that naproxen
      interacts with PI3K and inhibits its kinase activity. Pull-down binding assay
      data confirmed that PI3K directly binds with naproxen in vitro and ex vivo.
      Western blot data showed that naproxen decreased phosphorylation of Akt, and
      subsequently decreased Akt signaling in UM-UC-5 and UM-UC-14 urinary bladder
      cancer cells. Furthermore, naproxen suppressed anchorage-independent cell growth
      and decreased cell viability by targeting PI3K in both cell lines. Naproxen
      caused an accumulation of cells at the G1 phase mediated through cyclin-dependent
      kinase 4, cyclin D1, and p21. Moreover, naproxen induced significant apoptosis,
      accompanied with increased levels of cleaved caspase-3, caspase-7, and PARP in
      both cell types. Naproxen-induced cell death was mainly because of apoptosis in
      which a prominent downregulation of Bcl-2 and upregulation of Bax were involved.
      Naproxen also caused apoptosis and inhibited Akt phosphorylation in rat urinary
      bladder cancers induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

PMID- 24327723
TI  - Prevalence and predictors of cytomegalovirus retinitis in HIV-infected patients
      with low CD4 lymphocyte counts in Vietnam.
AB  - We describe the results of a study to determine the prevalence and
      characteristics of cytomegalovirus (CMV) retinitis among HIV-infected patients in
      Vietnam. We conducted a cross-sectional prospective study of patients with CD4
      lymphocyte count <=100 cells/mm(3)recruited from public HIV clinics. The
      diagnosis was made by a trained ophthalmologist using slit lamp biomicroscopy and
      corroborated on fundus photography. A total of 201 patients were screened. The
      median age was 32 years, 77% were men, median CD4 count was 47 cells/mm(3), and
      62% were on antiretroviral treatment. Prevalence of CMV retinitis was 7% (14/201,
      95% CI 4-11%). CMV retinitis was not associated with age, gender, injection drug
      use, CD4 count, WHO clinical stage, or antiretroviral treatment status. Blurring
      of vision and reduced visual acuity <20/40 were associated with CMV retinitis,
      but only 29% of patients with the diagnosis reported blurry vision and only 64%
      had abnormal vision. On multivariate analysis, the sole predictor for CMV
      retinitis was decreased visual acuity (OR 22.8,p < 0.001). In Ho Chi Minh City,
      CMV retinitis was found in 7% of HIV-infected patients with low CD4. HIV-infected
      patients with a CD4 count <100/mm(3)or who develop blurring of vision in Vietnam
      should be screened for CMV retinitis. 

PMID- 24327722
TI  - Serum glycan signatures of gastric cancer.
AB  - Glycomics, a comprehensive study of glycans expressed in biologic systems, is
      emerging as a simple yet highly sensitive diagnostic tool for disease onset and
      progression. This study aimed to use glycomics to investigate glycan markers that
      would differentiate patients with gastric cancer from those with nonatrophic
      gastritis. Patients with duodenal ulcer were also included because they are
      thought to represent a biologically different response to infection with
      Helicobacter pylori, a bacterial infection that can cause either gastric cancer
      or duodenal ulcer. We collected 72 serum samples from patients in Mexico City
      that presented with nonatrophic gastritis, duodenal ulcer, or gastric cancer. N
      glycans were released from serum samples using the generic method with PNGase F
      and were analyzed by matrix-assisted laser desorption/ionization Fourier
      transform-ion cyclotron resonance mass spectrometry. The corresponding glycan
      compositions were calculated based on accurate mass. ANOVA-based statistical
      analysis was performed to identify potential markers for each subgroup. Nineteen
      glycans were significantly different among the diagnostic groups. Generally,
      decreased levels of high-mannose-type glycans, glycans with one complex type
      antenna, bigalactosylated biantennary glycans, and increased levels of
      nongalactosylated biantennary glycans were observed in gastric cancer cases.
      Altered levels of serum glycans were also observed in duodenal ulcer, but
      differences were generally in the same direction as gastric cancer. Serum glycan
      profiles may provide biomarkers to differentiate gastric cancer cases from
      controls with nonatrophic gastritis. Further studies will be needed to validate
      these findings as biomarkers and identify the role of protein glycosylation in
      gastric cancer pathology.

PMID- 24327724
TI  - Incidence and predictive factors of depression among patients with HIV infection
      in Guadeloupe: 1988-2009.
AB  - A retrospective cohort study was conducted to determine the incidence and the
      predictive factors of depression in a cohort of 2737 HIV/AIDS-infected patients
      in Guadeloupe followed for a total of 8402 patient-years. The incidence rate of
      first observed depression was 2.2 per 100 person-years (95% confidence interval
      [CI], 1.9-2.6). A single failure Cox proportional hazards model showed that the
      1997-2000 inclusion period (hazard ratio [HR] = 1.60; 95% CI = 1.10-2.40;p =
      0.01), the 2001-2009 inclusion period (HR = 1.50; 95% CI = 1.02-2.40;p = 0.04),
      the more advanced CDC stage (HR = 2.30; 95% CI = 1.30-3.10;p = 0.000) and the
      annual frequency of visits > 10 (HR = 2.30; 95% CI = 1.70-3.30;p = 0.000) were
      associated with an increased risk of depression. Incidence of depression in this
      HIV cohort was high and the hazard function showed three peaks of depression (2,
      7 and 12 years). Physicians should be vigilant to psychological distress
      throughout life with HIV. 

PMID- 24327725
TI  - Do attendees at sexual health and HIV clinics prefer to be called in by name or
      number?
AB  - Calling patients in from the waiting area is an important aspect of the initial
      medical encounter. According to national and international guidelines, clinics
      should decide on an appropriate way of calling patients in from the waiting room
      for consultations; however, no preference is actually recommended. A survey was
      carried out to see if patients were happy to be called in by number, first name,
      surname, full name, or title (Mr/Mrs/Miss/Ms) followed by surname. One hundred
      unselected patients were drawn from each clinic including; a genito-urinary
      medicine (GUM), a co-located GUM (cGUM) and co-located reproductive health (cRH),
      an HIV and a reproductive health (RH) clinic. Patients from the GUM, cGUM, cRH
      and RH clinics preferred to be called in by number rather than full name or
      title. Patients from the cRH clinic also preferred number to first name. In
      contrast, patients from the HIV clinics preferred to be called in by first name
      rather than number, surname, full name or title. Following this survey it would
      appear that number would be the most popular method of calling patients in sexual
      and reproductive health clinics and first name is the choice in HIV clinics. 

PMID- 24327726
TI  - Trends in clinical characteristics of HIV-infected patients initiating
      antiretroviral therapy in Shanghai from 2006 to 2011.
AB  - This study aimed to characterise the clinical characteristics of HIV-infected
      patients accessing antiretroviral therapy (ART) in Shanghai, China, from 2006 to
      2011. We retrospectively reviewed the records of patients who initiated ART in
      Shanghai during the 6-year period of 2006 through 2011. The median age at ART
      initiation decreased from 41 years in 2008 to 38 years in 2011. The median CD4
      counts at ART initiation rose from 65 cells/mm(3)in 2006 to 203 cells/mm(3)in
      2011. The proportion of patients with CD4 counts <200 cells/mm(3)at ART
      initiation decreased from 88.5% in 2006 to 49.6% in 2011. The proportion of
      patients starting stavudine-based regimens of stavudine/lamivudine/efavirenz and
      stavudine/lamivudine/nevirapine fell from 49.2% in 2006 to 23.4% in 2011. The
      proportion of patients starting nevirapine-based regimens of
      zidovudine/lamivudine/nevirapine and stavudine/lamivudine/nevirapine fell from
      44.3% in 2006 to 16.5% in 2011. The study reflects that the clinical
      characteristics of the patients initiating ART in Shanghai have changed over
      time; ART was increasingly provided in patients with higher CD4 counts; and the
      regimens containing stavudine were prescribed less frequently. Strategies to
      facilitate early access to ART and further reduction in stavudine use are needed.

PMID- 24327727
TI  - beta1 integrin: Critical path to antiangiogenic therapy resistance and beyond.
AB  - Angiogenesis is an important tissue-level program supporting the growth of highly
      aggressive cancers and early-stage metastases. However, rapid emergence of
      resistance to antiangiogenic therapies, such as bevacizumab, greatly limits the
      clinical utility of these promising approaches. The mechanisms of resistance to
      antiangiogenic therapy remain incompletely understood. The tumor microenvironment
      has been demonstrated to be a source of broad therapeutic resistance in multiple
      cancers. Much of the interaction between the cells comprising a tumor and their
      microenvironment is driven by integrins. Notably, signaling downstream of
      integrins in tumor cells promotes fundamental programs vital to aggressive cancer
      biology, including proliferation, growth, invasion, and survival signaling. These
      functions then can contribute to malignant phenotypes, including metastasis,
      therapy resistance, epithelial-to-mesenchymal transition, and angiogenesis.
      Accordingly, we found beta1 integrin to be functionally upregulated in tumor
      specimens from patients after bevacizumab failure and in xenograft models of
      bevacizumab resistance. Inhibition of beta1 in tumor cells with stable gene
      knockdown or treatment with OS2966, a neutralizing beta1 integrin monoclonal
      antibody, attenuated aggressive tumor phenotypes in vitro and blocked growth of
      bevacizumab-resistant tumor xenografts in vivo. Thus, beta1 integrins promote
      resistance to antiangiogenic therapy through potentiation of multiple malignant
      programs facilitated by interactions with the tumor microenvironment. The
      elucidation of this mechanism creates an outstanding opportunity for improving
      patient outcomes in cancer.

PMID- 24327729
TI  - The relationship between serum bilirubin concentration and coronary slow flow.
AB  - BACKGROUND: The pathophysiology of coronary slow flow (CSF) has not been clearly
      identified, although multiple abnormalities including arteritis, endothelial
      dysfunction, and atherothrombosis have been reported. Several studies have
      demonstrated that higher serum bilirubin inhibits the inflammation and
      proliferation of vascular smooth muscle cells; in addition, there is a
      relationship between serum bilirubin and cardiovascular disease. However, the
      relationship between bilirubin and CSF is still unknown. In our study, we
      compared serum bilirubin concentrations between CSF patients and controls.
      METHODS: The study included 50 CSF patients (19 male, mean age 65.6 +/- 13.7
      years) and 30 controls (10 male, mean age 57.86 +/- 11.6 years). Concurrent
      routine biochemical tests and leukocyte count, hemoglobin, hematocrit, and
      platelet count on whole blood count were performed in patients that underwent a
      coronary angiogram. These parameters were compared between groups. RESULTS: No
      statistically significant difference was found between the two groups in terms of
      basic characteristics. Total, direct, and indirect serum bilirubin levels were
      significantly lower among CSF patients than controls (14.0 +/- 12.0 versus 6.15
      +/- 6.8, 5.6 +/- 3.4 versus 2.6 +/- 1.7, and 8.4 +/- 8.5 versus 3.6 +/- 3.4
      umol/l; all p < 0.001, respectively). CONCLUSIONS: The study revealed a
      relationship between serum bilirubin and CSF.

PMID- 24327731
TI  - Constrictive pericarditis in a young patient with very thick pericardium
      initially diagnosed as cirrhosis.
AB  - Constrictive pericarditis (CP) is a disease of pericardium that restricts filling
      of the heart. Patients with CP generally present to hospitals with exercise
      induced dyspnea, pretibial edema and abdominal ascites, and it is sometimes
      mistakenly diagnosed as liver or renal disease. Pericardial thickening, which is
      defined as more than 4 mm in diameter, is observed in nearly 80% of patients. In
      the present paper, we describe a case of CP with a pericardial thickness of 12 mm
      that was initially diagnosed as cirrhosis. 

PMID- 24327730
TI  - Sevelamer revisited: pleiotropic effects on endothelial and cardiovascular risk
      factors in chronic kidney disease and end-stage renal disease.
AB  - Endothelial dysfunction underlies multiple cardiovascular consequences of chronic
      kidney disease (CKD) and antecedent diabetes or hypertension. Endothelial insults
      in CKD or end-stage renal disease (ESRD) patients include uremic toxins, serum
      uric acid, hyperphosphatemia, reactive oxygen species, and advanced glycation
      endproducts (AGEs). Sevelamer carbonate, a calcium-free intestinally nonabsorbed
      polymer, is approved for hyperphosphatemic dialysis patients in the US and
      hyperphosphatemic stage 3-5 CKD patients in many other countries. Sevelamer has
      been observed investigationally to reduce absorption of AGEs, bacterial toxins,
      and bile acids, suggesting that it may reduce inflammatory, oxidative, and
      atherogenic stimuli in addition to its on-label action of lowering serum
      phosphate. Some studies also suggest that noncalcium binders may contribute less
      to vascular calcification than calcium-based binders. Exploratory sevelamer
      carbonate use in patients with stages 2-4 diabetic CKD significantly reduced
      HbA1c, AGEs, fibroblast growth factor (FGF)-23, and total and low-density
      lipoprotein (LDL) cholesterol versus calcium carbonate; inflammatory markers
      decreased and defenses against AGEs increased. Sevelamer has also been observed
      to reduce circulating FGF-23, potentially reducing risk of left ventricular
      hypertrophy. Sevelamer but not calcium-based binders in exploratory studies
      increases flow-mediated vasodilation, a marker of improved endothelial function,
      in patients with CKD. In contrast, lanthanum carbonate and calcium carbonate
      effects on FMV did not differ in hemodialysis recipients. The recent independent
      CKD randomized trial compared sevelamer versus calcium carbonate in predialysis
      CKD patients (investigational in the US, on-label in European participants);
      sevelamer reduced 36-month mortality and the composite endpoint of mortality or
      dialysis inception. Similarly, independent-HD in incident dialysis patients
      showed improved survival with 24 months of sevelamer versus calcium-based
      binders. This review discusses recent exploratory evidence for pleiotropic
      effects of sevelamer on endothelial function in CKD or ESRD. Endothelial effects
      of sevelamer may contribute mechanistically to the improved survival observed in
      some studies of CKD and ESRD patients.

PMID- 24327732
TI  - Scalable culture of human pluripotent stem cells in 3D.

PMID- 24327733
TI  - PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1.
AB  - The PI3K pathway is genetically altered in excess of 70% of breast cancers,
      largely through PIK3CA mutation and HER2 amplification. Preclinical studies have
      suggested that these subsets of breast cancers are particularly sensitive to PI3K
      inhibitors; however, the reasons for this heightened sensitivity are mainly
      unknown. We investigated the signaling effects of PI3K inhibition in PIK3CA
      mutant and HER2 amplified breast cancers using PI3K inhibitors currently in
      clinical trials. Unexpectedly, we found that in PIK3CA mutant and HER2 amplified
      breast cancers sensitive to PI3K inhibitors, PI3K inhibition led to a rapid
      suppression of Rac1/p21-activated kinase (PAK)/protein kinase C-RAF (C-RAF)/
      protein kinase MEK (MEK)/ERK signaling that did not involve RAS. Furthermore,
      PI3K inhibition led to an ERK-dependent up-regulation of the proapoptotic
      protein, BIM, followed by induction of apoptosis. Expression of a constitutively
      active form of Rac1 in these breast cancer models blocked PI3Ki-induced down
      regulation of ERK phosphorylation, apoptosis, and mitigated PI3K inhibitor
      sensitivity in vivo. In contrast, protein kinase AKT inhibitors failed to block
      MEK/ERK signaling, did not up-regulate BIM, and failed to induce apoptosis.
      Finally, we identified phosphatidylinositol 3,4,5-trisphosphate-dependent Rac
      exchanger 1 (P-Rex1) as the PI(3,4,5)P3-dependent guanine exchange factor for
      Rac1 responsible for regulation of the Rac1/C-RAF/MEK/ERK pathway in these cells.
      The expression level of P-Rex1 correlates with sensitivity to PI3K inhibitors in
      these breast cancer cell lines. Thus, PI3K inhibitors have enhanced activity in
      PIK3CA mutant and HER2 amplified breast cancers in which PI3K inhibition down
      regulates both the AKT and Rac1/ERK pathways. In addition, P-Rex1 may serve as a
      biomarker to predict response to single-agent PI3K inhibitors within this subset
      of breast cancers. 

PMID- 24327735
TI  - Governance of quality of care: a qualitative study of health service boards in
      Victoria, Australia.
AB  - OBJECTIVES: To describe the engagement of health service boards with quality-of
      care issues and to identify factors that influence boards' activities in this
      area. METHODS: We conducted semistructured interviews with 35 board members and
      executives from 13 public health services in Victoria, Australia. Interviews
      focused on the role currently played by boards in overseeing quality of care. We
      also elicited interviewees' perceptions of factors that have influenced their
      current approach to governance in this area. Thematic analysis was used to
      identify key themes from interview transcripts. RESULTS: Virtually all
      interviewees believed boards had substantial opportunities to influence the
      quality of care delivered within the service, chiefly through setting priorities,
      monitoring progress, holding staff to account and shaping culture. Perceived
      barriers to leveraging this influence included insufficient resources, gaps in
      skills and experience among board members, inadequate information on performance
      and regulatory requirements that miss the mark. Interviewees converged on four
      enablers of more effective quality governance: stronger regional collaborations;
      more tailored board training on quality issues; smarter use of reporting and
      accreditation requirements; and better access to data that was reliable,
      longitudinal and allowed for benchmarking against peer organisations.
      CONCLUSIONS: Although health service boards are eager to establish quality of
      care as a governance priority, several obstacles are blocking progress. The
      result is a gap between the rhetoric of quality governance and the reality of
      month-to-month activities at the board level. The imperative for effective board
      level engagement in this area cannot be met until these barriers are addressed.

PMID- 24327734
TI  - Cholinergic left-right asymmetry in the habenulo-interpeduncular pathway.
AB  - The habenulo-interpeduncular pathway, a highly conserved cholinergic system, has
      emerged as a valuable model to study left-right asymmetry in the brain. In larval
      zebrafish, the bilaterally paired dorsal habenular nuclei (dHb) exhibit prominent
      left-right differences in their organization, gene expression, and connectivity,
      but their cholinergic nature was unclear. Through the discovery of a duplicated
      cholinergic gene locus, we now show that choline acetyltransferase and vesicular
      acetylcholine transporter homologs are preferentially expressed in the right dHb
      of larval zebrafish. Genes encoding the nicotinic acetylcholine receptor subunits
      alpha2 and beta4 are transcribed in the target interpeduncular nucleus (IPN),
      suggesting that the asymmetrical cholinergic pathway is functional. To confirm
      this, we activated channelrhodopsin-2 specifically in the larval dHb and
      performed whole-cell patch-clamp recording of IPN neurons. The response to
      optogenetic or electrical stimulation of the right dHb consisted of an initial
      fast glutamatergic excitatory postsynaptic current followed by a slow-rising
      cholinergic current. In adult zebrafish, the dHb are divided into discrete
      cholinergic and peptidergic subnuclei that differ in size between the left and
      right sides of the brain. After exposing adults to nicotine, fos expression was
      activated in subregions of the IPN enriched for specific nicotinic acetylcholine
      receptor subunits. Our studies of the newly identified cholinergic gene locus
      resolve the neurotransmitter identity of the zebrafish habenular nuclei and
      reveal functional asymmetry in a major cholinergic neuromodulatory pathway of the
      vertebrate brain. 

PMID- 24327736
TI  - Weissella confusa septicemia in a foal.
AB  - Weissella confusa is a Gram-positive bacterium that has been identified in
      environmental and food samples from around the world. Rare cases of bacteremia in
      immunocompromised people have been reported. A 2-day-old foal was presented for
      weakness and suspected sepsis. Blood culture yielded pure growth of a Gram
      positive coccobacillus, which was identified as W. confusa through sequencing of
      the 16S ribosomal DNA. Although the foal initially responded to antimicrobial
      therapy with ceftiofur and metronidazole, it later developed septic complications
      of the right tarsocrural joint and right digital flexor tendon sheath and was
      euthanized. Postmortem examination and histology revealed subcutaneous icterus,
      severe diffuse interstitial pneumonia, septic synovitis, necrotizing vasculitis
      with marked thrombosis and hemorrhage in the medial digital vessels of the right
      hind limb, and ischemic necrosis of the right hind hoof laminae. Gram-positive,
      coccobacilli were observed in the vascular lesion. 

PMID- 24327737
TI  - Distribution of lymphoid depletion and viral antigen in alpacas experimentally
      infected with Bovine viral diarrhea virus 1.
AB  - It was hypothesized that acute postnatal Bovine viral diarrhea virus 1 (BVDV-1)
      infection leads to leukopenia and lymphoid depletion of gut-associated lymphoid
      tissues similar to acute disease in calves. The objectives of the current study
      were to characterize the pathologic effects, viremia, viral shedding, and viral
      antigen deposition in 6-24-month-old, acutely infected alpacas following
      experimental infection with noncytopathic BVDV-1 subgenotype 1b (BVDV C0-6). The
      BVDV-1 isolate was obtained from a cria with naturally occurring persistent
      infection. Lymphocytopenia occurred 3-7 days postinfection, with a 50% reduction
      in peripheral lymphocytes in infected alpacas. Depletion of B-cell populations in
      gut-associated lymphoid tissues was evident microscopically. Populations of T
      cells in parafollicular zones and in nodular aggregates along the superficial
      submucosa remained intact. The BVDV antigen was deposited most consistently in
      submucosal gastrointestinal aggregated lymphoid tissues of ileum, proximal colon,
      and stomach compartment three. Viral antigen was more variably evident in other
      lymphoid tissues. Antigen distribution correlated well with histologic lesions in
      gastrointestinal aggregated lymphoid tissues, confirming the role of virus in
      lymphoid depletion. Nasal shedding was detected in all challenged alpacas on day
      6 and in 4 out of 12 challenged alpacas on day 9. Viremia was present as early as
      day 3, and present in all challenged alpacas on days 5, 6, 7, and 9
      postchallenge. Lymphocytopenia and depletion of gastrointestinal aggregated
      lymphoid tissues associated with acute BVDV-1 infection likely results in immune
      compromise and is expected to exacerbate concurrent infections even though
      uncomplicated BVDV-1 infection was clinically unapparent. 

PMID- 24327738
TI  - Kisspeptin and energy balance in reproduction.
AB  - Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion.
      Kisspeptin neurons are now recognized as a central pathway responsible for
      conveying key homeostatic information to GNRH neurons. This pathway is likely to
      mediate the well-established link between energy balance and reproductive
      function. Thus, in states of severely altered energy balance (either negative or
      positive), fertility is compromised, as is Kiss1 expression in the arcuate
      nucleus. A number of metabolic modulators have been proposed as regulators of
      kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and
      neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or
      indirectly will be discussed. Moreover, whether the stimulatory role of leptin on
      reproduction is mediated by kisspeptin directly will be questioned. Furthermore,
      in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r)
      is also expressed in other areas of the brain, as well as in the periphery,
      suggesting alternative roles for kisspeptin signaling outside of reproduction.
      Interestingly, kisspeptin neurons are anatomically linked to, and can directly
      excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons.
      Thus, kisspeptin may have a direct role in regulating energy balance. Although
      data from Kiss1r knockout and WT mice found no differences in body weight, recent
      data indicate that kisspeptin may still play a role in food intake and glucose
      homeostasis. Thus, in addition to regulating reproduction, and mediating the
      effect of energy balance on reproductive function, kisspeptin signaling may also
      be a direct regulator of metabolism. 

PMID- 24327739
TI  - Traumatic complex splenic arteriovenous fistula causing prehepatic portal
      hypertension and variceal bleeding: the importance of the diagnosis for the
      endovascular treatment approach.
AB  - We report a case of a 68-year-old female patient presenting with portal
      hypertension and variceal bleeding in the absence of any liver disease. After
      performing a computed tomography angiogram, the cause of her condition was
      identified to be a splenic arteriovenous fistula (SAVF). After confirming the
      findings with angiography, we opted to treat the condition with coil embolization
      as an alternative to a more invasive surgical treatment. Coil embolization of the
      SAVF was performed successfully resulting in the improvement of the patient's
      variceal congestion. Our case highlights the importance of identifying SAVF as a
      potentially curable cause of variceal bleeding in the absence of liver disease.
      Seeking this diagnosis is of utmost importance since it completely changes the
      endovascular approach and management of these patients with variceal bleeding. We
      describe a minimally invasive endovascular technique for treatment of these
      critically ill patients. 

PMID- 24327740
TI  - The accuracy of transcutaneous PCO2 in subjects with severe brain injury: a
      comparison with end-tidal PCO2.
AB  - BACKGROUND: In patients suffering from brain injury, end-tidal PCO2 (PETCO2 )
      monitoring is controversial, but transcutaneous PCO2 (PtcCO2 ), which is
      noninvasive and utilizes immediate display, may be an alternative method. We
      hypothesized that PtcCO2 would be more accurate than PETCO2 for monitoring PaCO2
      in patients with severe brain injury. METHODS: A prospective observational study
      included consecutive mechanically ventilated adult subjects who had acute brain
      injury and an arterial catheter in place. When an arterial blood gas analysis was
      required, the PETCO2 and PtcCO2 values were simultaneously recorded. The
      agreement between the PETCO2 , PtcCO2 , and PaCO2 measurements (reference) was
      determined using the Bland-Altman method. The number of outliers defined by the
      formula ([PETCO2 or PtcCO2 ] - PaCO2 ) > +/- 4 mm Hg indicated the proportion of
      measurements that were considered clinically unacceptable. RESULTS: A total of 25
      subjects were included in the study, and 85 simultaneous measurements of PaCO2 ,
      PtcCO2 , and PETCO2 were obtained. The bias and precision between PaCO2 and
      PtcCO2 were -0.75 and 6.23 mm Hg, respectively. The limits of agreement ranged
      from -12.97 to 11.47 mm Hg. The bias and precision between PaCO2 and PETCO2 were
      0.68 and 5.82 mm Hg, respectively. The limits of agreement ranged from -10.72 to
      12.08 mm Hg. There were 34 (40%) outliers for the PtcCO2 sensor and 34 (40%)
      outliers for the PETCO2 sensor (P > .99). CONCLUSIONS: The accuracy of PtcCO2 was
      not superior to that of PETCO2 for assessing PCO2 levels and should not be used
      to monitor these levels in subjects with severe brain injury.

PMID- 24327741
TI  - Biphasic capnogram in a single-lung transplant recipient: a case report.
AB  - Capnography is a graphic representation of the carbon dioxide concentration in
      the airways plotted against time. We report an unusual biphasic-shaped capnogram
      in a single-lung transplant recipient. In keeping with the only 2 prior reports
      of which we are aware, we ascribe the unusual biphasic pattern to differential
      emptying of the native and transplanted lungs. This experience reminds
      respiratory clinicians of the value of capnometry as a monitoring tool and
      hopefully will heighten awareness regarding the diagnostic value of usual and
      unusual capnographic patterns.

PMID- 24327742
TI  - Necrotizing sarcoid granulomatosis with an uncommon manifestation:
      clinicopathological features and review of literature.
AB  - We report a rare case of an incidental diagnosis of necrotizing sarcoid
      granulomatosis (NSG) in a 60-y-old non-smoking male. The patient was admitted to
      the hospital for sudden back pain. Chest x-ray revealed areas of parenchymal
      consolidation and high-resolution computed tomography demonstrated a pulmonary
      nodular pattern with no lymph node enlargement. All laboratory and pulmonary
      function tests were normal. Bronchoscopy with bronchoalveolar lavage showed no
      sign of infection or specific inflammation. The diagnosis of NSG was made by
      histopathological examination of a surgical lung biopsy and by excluding other
      causes of granulomatous disease. In paucisymptomatic/asymptomatic patients, as in
      our case, therapy is not necessary, with a good prognosis and complete recovery.
      NSG is a rare systemic disease similar to sarcoidosis and Wegener's
      granulomatosis with a benign clinical course and should always be considered for
      patients with nodular pulmonary lesions even with subclinical or uncommon
      features. 

PMID- 24327743
TI  - Endurance time is the most responsive exercise measurement in idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Although pulmonary rehabilitation (PR) has been reported to improve
      exercise capacity in patients with idiopathic pulmonary fibrosis, it is unknown
      which exercise measurement is the most responsive for evaluation of PR efficacy.
      The purpose of this study was to compare the responsiveness of 5 exercise
      measurements by evaluating the efficacy of PR in subjects with idiopathic
      pulmonary fibrosis. METHODS: We conducted a prospective observational study in
      which 53 subjects with idiopathic pulmonary fibrosis were enrolled. The PR group
      underwent a 10-week out-patient PR program. The control group was observed
      without any additional intervention, including PR. Five exercise measurements
      (endurance time [ET], peak work rate, peak oxygen consumption [VO2 ], 6-min walk
      distance, and incremental shuttle walk distance) were evaluated at baseline and
      after 10 weeks. The effect size was used for the assessment of responsiveness.
      RESULTS: In each group, 24 subjects completed the 5 measurements at baseline and
      after 10 weeks. The changes in ET (PR: 181.6%; control: -8.2%), peak VO2 (PR:
      7.6%; control: -5.4%), peak work rate (PR: 15.1%; control: -5.1%), 6-min walk
      distance (PR: 6.0%; control: -3.8%), and incremental shuttle walk distance (PR:
      9.1%; control: -5.1%) were significantly different between the groups after 10
      weeks (P < .05). In the PR group, ET showed the most striking improvement among
      the 5 measurements (P < .05), and its effect size was as large as 2.96, whereas
      those of the others were all < 0.5. CONCLUSIONS: ET is the most responsive
      exercise measurement for evaluating PR efficacy in patients with idiopathic
      pulmonary fibrosis.

PMID- 24327744
TI  - Effect of mask dead space and occlusion of mask holes on delivery of nebulized
      albuterol.
AB  - BACKGROUND: Infants and children with respiratory conditions are often prescribed
      bronchodilators. Face masks are used to facilitate the administration of
      nebulized therapy in patients unable to use a mouthpiece. Masks incorporate holes
      into their design, and their occlusion during aerosol delivery has been a common
      practice. Masks are available in different sizes and different dead volumes. The
      aim of this study was to compare the effect of different degrees of occlusion of
      the mask holes and different mask dead space on the amount of nebulized albuterol
      available at the mouth opening in a model of a spontaneously breathing child.
      METHODS: A breathing simulator mimicking infant (tidal volume [VT] = 50 mL,
      breathing frequency = 30 breaths/min, inspiratory-expiratory ratio [I:E] = 1:3),
      child (VT = 155 mL, breathing frequency = 25 breaths/min, I:E = 1:2), and adult
      (VT = 500 mL, breathing frequency = 15 breaths/min, I:E = 1:2) breathing patterns
      was connected to a collection filter hidden behind a face plate. A pediatric size
      mask and an adult size mask connected to a continuous output jet nebulizer were
      sealed to the face plate. Three nebulizers were loaded with albuterol sulfate
      (2.5 mg/3 mL) and operated with 6 L/min compressed air for 5 min. Experiments
      were repeated with different degrees of occlusion (0%, 50%, and 90%). Albuterol
      was extracted from the filter and measured with a spectrophotometer at 276 nm.
      RESULTS: Occlusion of the holes in the large mask did not increase the amount of
      albuterol in any of the breathing patterns. The amount of albuterol captured at
      the mouth opening did not change when the small mask was switched to the large
      mask, except with the breathing pattern of a child, and when the holes in the
      mask were 50% occluded (P = .02). CONCLUSIONS: Neither decreasing the dead space
      of the mask nor occluding the mask holes increased the amount of nebulized
      albuterol captured at the mouth opening.

PMID- 24327745
TI  - Better ventilator settings using a computerized clinical tool.
AB  - BACKGROUND: The Acute Respiratory Distress Syndome (ARDS) Network low tidal
      volume (VT) trial paved the ground for mechanically ventilating ARDS patients
      with a VT of 6 mL/kg ideal body weight (IBW). Although there is no consensus that
      a low VT is advantageous in non-ARDS patients,it is accepted that high VT should
      be avoided. Because compliance rates with ventilator recommendations are 30%,
      there is a need for process improvement. We postulated that a computerized screen
      prompt that recommended VT based on height would improve compliance with low
      VT.During ventilator order entry, the computerized decision tool prompts the
      clinician and encourages ventilation of patients at 8 mL/kg IBW, and 6 mL/kg IBW
      for patients with ARDS. METHODS: A retrospective review was performed on patients
      who required volume controlled mechanical ventilation over a 3-y period. Subjects
      were chosen randomly from the respiratory records of 6 different ICUs at a single
      tertiary care academic center. Half of the charts selected were before
      intervention of on-screen prompt, and the other half were after implementation of
      the computerized decision tool. RESULTS: The initial set VT ranged from 6.26 to
      13.45 mL/kg IBW, with a mean of 8.92 mL/kg. After implementation of the on-screen
      prompt, mean VT decreased by 0.84 mL/kg to 8.07 mL/kg (P= .001) with a lower
      range of 4.73-11.56 mL/kg IBW. We also noted a significant decrease in the number
      of subjects placed on an initial VT > 10 mL/kg IBW from 20% to 4% (P= .003).
      CONCLUSIONS: A computerized clinical decision tool with the preferred initial VT
      settings based on the patients' sex and height is a safe and reliable way to
      increase low VT strategy compliance across multiple ICUs. Its limitations are
      similar to those shared by other computer-generated prompts.

PMID- 24327746
TI  - Functional respiratory imaging as a tool to personalize respiratory treatment in
      patients with unilateral diaphragmatic paralysis.
AB  - A completely different treatment approach was chosen for 2 patients with
      unilateral diaphragmatic paralysis and complaints of dyspnea despite similar
      anatomic and physiologic abnormalities. These decisions were supported by results
      obtained by functional respiratory imaging (FRI). FRI generated functional
      information on lobar ventilation and local drug deposition. In the first patient,
      some lobes were poorly ventilated, and drug deposition simulation showed that
      some regions were undertreated. This patient underwent diaphragmatic plication to
      restore ventilation. In the second patient, all lobes were still ventilated. A
      conservative approach with regular follow-ups was chosen to wait for spontaneous
      recovery of the diaphragmatic function. Both patients improved subjectively and
      objectively. These cases demonstrate how novel medical imaging techniques such as
      FRI can be used to personalize respiratory treatment in patients with unilateral
      diaphragmatic paralysis. 

PMID- 24327747
TI  - Evaluation of transport ventilators at mild simulated altitude: a bench study in
      a hypobaric chamber.
AB  - BACKGROUND: Previous studies on ventilators used for air transport showed
      significant effects of altitude, in particular with regard to accuracy of the
      tidal volume (VT) and breathing frequency. The aim of the study was to evaluate
      transport ventilators under hypobaric conditions. METHODS: We conducted a bench
      study of 6 transport ventilators in a Comex hypobaric chamber to simulate mild
      altitude (1,500 m [4,920 feet] and 2,500 m [8,200 feet]). The ventilators were
      connected to a test lung to evaluate their accuracy: (1) to deliver a set VT
      under normal resistance and compliance conditions at F(IO2) = 0.6 and 1, (2) to
      establish a set PEEP (0, 5, 10, and 15 cm H2O), and (3) to establish a set
      inspiratory pressure in pressure controlled mode, (4) at a F(IO2) setting, and
      (5) and at a frequency setting. RESULTS: Four ventilators kept an average
      relative error in VT of < 10% without effect of altitude. The Medumat ventilator
      was affected by the altitude only at F(IO2) = 1. The Osiris 3 ventilator had >
      40% error even at 1,500 m. We found no change in frequency as a function of
      altitude for any ventilators studied. No clinically important differences were
      found between all altitudes with the PEEP or inspiratory pressure setting.
      Although F(IO2) was affected by altitude, the average error did not exceed 11%,
      and it is unclear whether this fact is an experimental artifact. CONCLUSIONS: We
      have shown that most of the new transport ventilators tested require no setting
      adjustment at moderate altitude and are as safe at altitude as at sea level under
      normal respiratory conditions. Older technologies still deliver more volume with
      altitude in volumetric mode.

PMID- 24327748
TI  - Clinical diagnosis of invasive pulmonary aspergillosis in a non-neutropenic
      critically ill patient.

PMID- 24327749
TI  - Procalcitonin kinetics and nosocomial pneumonia in older patients.
AB  - BACKGROUND: Early identification of treatment failure for nosocomial pneumonia
      remains a major challenge. The goal of this study was to test whether
      procalcitonin kinetics can be used to assess the clinical efficacy in older
      critically ill patients with nosocomial pneumonia. METHODS: A prospective
      observational study was conducted with 60 subjects (>= 65 y old) admitted to the
      ICU with severe nosocomial pneumonia. Serum procalcitonin was measured on days 0,
      3, and 7 and at the end of treatment. The procalcitonin time course was analyzed
      according to the therapeutic efficacy. RESULTS: Procalcitonin levels were
      elevated in all subjects (n = 60) on day 0, and the median level (range) was 2.5
      (0.8-42.7) MUg/L. There were no differences in procalcitonin between the improved
      subjects (n = 41) and those without improvement (n = 19) on day 0 (P > .05).
      However, lower procalcitonin levels on days 3 and 7 and at the end of treatment
      (all P < .05) and greater rates of procalcitonin decline between days 0 and 3
      (DeltaPCT(d3)%; 29.5 +/- 10.8% vs 15.1 +/- 5.9%, P = .009) were observed in the
      improved subjects compared with those with no improvement. DeltaPCT(d3)% was the
      best single predictor of efficacy (area under the curve of 0.79, P < .001) and
      had a sensitivity of 75.7% and a specificity of 72.0% with a threshold of 26.2%.
      By comparison, traditional parameters and absolute procalcitonin failed to
      predict treatment response (P > .05). Indeed, the combination of DeltaPCT(d3)% >
      26.2% and a modified Clinical Pulmonary Infection Score of < 6 points improved
      the predictive value (area under the curve of 0.89, sensitivity of 81.3%,
      specificity of 86.5%). CONCLUSIONS: Procalcitonin levels were not influenced by
      aging, and procalcitonin kinetics might help to identify treatment failure.
      DeltaPCT(d3)% in combination with the Clinical Pulmonary Infection Score has been
      shown to be a marker of clinical efficacy at an earlier stage.

PMID- 24327751
TI  - An upgraded track structure model: experimental validation.
AB  - The track nanodosemeter developed at the National Laboratories of Legnaro (LNL),
      Italy allows the direct investigation of the properties of particle tracks, by
      measuring ionisation-cluster-size distributions caused by ionising particles
      within a 'nanometre-sized' target volume while passing it at a well-specified
      impact parameter. To supplement the measurements, a dedicated Monte Carlo code
      was developed which is able to reproduce the general shape of measured cluster
      size distributions with a satisfactory quality. To reduce the still existing
      quantitative differences between measured and simulated data, the validity of
      cross sections used in the Monte Carlo model was revisited again, taking into
      account the large amount of data available now from recent track structure
      measurements at LNL. Here, special emphasis was laid on a deeper and detailed
      investigation of the cross sections applied to calculate the energy of secondary
      electrons after impact ionisation of primary particles: the cross sections due to
      the HKS model and the so-called Rudd model. Representative results for 240 MeV
      (12)C-ions are presented. 

PMID- 24327750
TI  - A new regulatory pathway of mRNA export by an F-box protein, Mdm30.
AB  - Mdm30, an F-box protein in yeast, has been recently shown to promote mRNA export.
      However, it remains unknown how Mdm30 facilitates mRNA export. Here, we show that
      Mdm30 targets the Sub2 component of the TREX (Transcription/Export) complex for
      ubiquitylation and subsequent proteasomal degradation. Such a targeted
      degradation of Sub2 enhances the recruitment of the mRNA export adaptor, Yra1, to
      the active genes to promote mRNA export. Together, these results elucidate that
      Mdm30 promotes mRNA export by lowering Sub2's stability and consequently
      enhancing Yra1 recruitment, thus illuminating new regulatory mechanisms of mRNA
      export by Mdm30. 

PMID- 24327752
TI  - Track counting and thickness measurement of LR115 radon detectors using a
      commercial image scanner.
AB  - An original optical method for track counting and film thickness determination of
      etched LR115 radon detectors was developed. The method offers several advantages
      compared with standard techniques. In particular, it is non-destructive, very
      simple and rather inexpensive, since it uses a commercial scanner and a free
      software. The complete analysis and the calibration procedure carried out for the
      determination of radon specific activity are reported. A comparison with the
      results of spark counting defines the accuracy and the precision of the new
      technique. 

PMID- 24327753
TI  - New radiation protection calibration facility at CERN.
AB  - The CERN radiation protection group has designed a new state-of-the-art
      calibration laboratory to replace the present facility, which is >20 y old. The
      new laboratory, presently under construction, will be equipped with neutron and
      gamma sources, as well as an X-ray generator and a beta irradiator. The present
      work describes the project to design the facility, including the facility
      placement criteria, the 'point-zero' measurements and the shielding study
      performed via FLUKA Monte Carlo simulations. 

PMID- 24327755
TI  - For Wayne S. Fenton, in memoriam.

PMID- 24327754
TI  - Prefrontal inefficiency is associated with polygenic risk for schizophrenia.
AB  - Considering the diverse clinical presentation and likely polygenic etiology of
      schizophrenia, this investigation examined the effect of polygenic risk on a well
      established intermediate phenotype for schizophrenia. We hypothesized that a
      measure of cumulative genetic risk based on additive effects of many genetic
      susceptibility loci for schizophrenia would predict prefrontal cortical
      inefficiency during working memory, a brain-based biomarker for the disorder. The
      present study combined imaging, genetic and behavioral data obtained by the Mind
      Clinical Imaging Consortium study of schizophrenia (n = 255). For each
      participant, we derived a polygenic risk score (PGRS), which was based on over
      600 nominally significant single nucleotide polymorphisms, associated with
      schizophrenia in a separate discovery sample comprising 3322 schizophrenia
      patients and 3587 control participants. Increased polygenic risk for
      schizophrenia was associated with neural inefficiency in the left dorsolateral
      prefrontal cortex after covarying for the effects of acquisition site, diagnosis,
      and population stratification. We also provide additional supporting evidence for
      our original findings using scores based on results from the Psychiatric Genomics
      Consortium study. Gene ontology analysis of the PGRS highlighted genetic loci
      involved in brain development and several other processes possibly contributing
      to disease etiology. Our study permits new insights into the additive effect of
      hundreds of genetic susceptibility loci on a brain-based intermediate phenotype
      for schizophrenia. The combined impact of many common genetic variants of small
      effect are likely to better reveal etiologic mechanisms of the disorder than the
      study of single common genetic variants. 

PMID- 24327756
TI  - Static and dynamic characteristics of cerebral blood flow during the resting
      state in schizophrenia.
AB  - BACKGROUND: The cerebral network that is active during rest and is deactivated
      during goal-oriented activity is called the default mode network (DMN). It
      appears to be involved in self-referential mental activity. Atypical functional
      connectivity in the DMN has been observed in schizophrenia. One hypothesis
      suggests that pathologically increased DMN connectivity in schizophrenia is
      linked with a main symptom of psychosis, namely, misattribution of thoughts.
      METHODS: A resting-state pseudocontinuous arterial spin labeling (ASL) study was
      conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia
      patients and 27 healthy controls. Using independent component analysis (ICA), the
      DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared
      between groups using a 2-sample t test. RESULTS: Schizophrenia patients showed
      decreased mean CBF in the frontal and temporal regions (P < .001). ICA
      demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = 
      16/-64/38) in patients than in controls (P < .001). CBF was not elevated in the
      respective regions. DMN connectivity in the precuneus was significantly
      correlated with the Positive and Negative Syndrome Scale scores (P < .01).
      CONCLUSIONS: In schizophrenia patients, the posterior hub--which is considered
      the strongest part of the DMN--showed increased DMN connectivity. We hypothesize
      that this increase hinders the deactivation of the DMN and, thus, the translation
      of cognitive processes from an internal to an external focus. This might explain
      symptoms related to defective self-monitoring, such as auditory verbal
      hallucinations or ego disturbances.

PMID- 24327757
TI  - Concise review: identifying limbal stem cells: classical concepts and new
      challenges.
AB  - The presence of a clear cornea is required for vision, and corneal epithelial
      cells play a key role. There is a long held view, supported by decades of study,
      that corneal epithelial stem cells reside at the limbus to regulate homeostatic
      cell turnover and wound healing. However, the identification of specific markers
      that allow the isolation and characterization of limbal stem cells remains
      elusive. Here, we review the classical concepts of limbal stem cell identity and
      highlight the current state of the field. 

PMID- 24327758
TI  - Evaluation of WHO screening algorithm for the presumptive treatment of
      asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya.
AB  - OBJECTIVES: The WHO recommends that men who have sex with men (MSM) reporting
      unprotected receptive anal intercourse (RAI) and either multiple partners or a
      partner with a sexually transmitted infection (STI) in the past 6 months should
      be presumptively treated for asymptomatic rectal Neisseria gonorrhoeae (NG) and
      Chlamydia trachomatis (CT) infections. We evaluated this recommendation in a
      cohort of 'high-risk' MSM in Coastal Kenya. METHODS: We assessed presence of
      genitourinary and rectal symptoms, and determined prevalence and 3-month
      incidence of rectal NG and CT infections. We performed nucleic acid amplification
      testing of urine and rectal swab samples collected from MSM followed
      prospectively, and assessed predictive values of the WHO algorithm at baseline
      screening. RESULTS: Of 244 MSM screened, 240 (98.4%) were asymptomatic, and 147
      (61.3%) reported any RAI in the past 6 months. Among 85 (35.4%) asymptomatic MSM
      meeting criteria for the WHO presumptive treatment (PT) recommendation, we
      identified 20 with rectal infections (six NG, 12 CT and two NG-CT co-infections).
      Among 62 asymptomatic MSM who did not meet criteria, we identified seven who were
      infected. The sensitivity and specificity of the WHO algorithm were 74.1% (95% CI
      53.7% to 88.9%) and 45.8% (95% CI 36.7% to 55.2%), respectively. The 3-month
      incidence of any rectal NG or CT infection in asymptomatic men reporting any RAI
      was 39.7 (95% CI 24.3 to 64.8) per 100 person-years. CONCLUSIONS: About one-third
      of asymptomatic MSM were eligible to receive PT for NG and CT infections. Among
      MSM who would qualify for PT of rectal STIs, the number needed to treat in order
      to treat one infection was four. Our results support the value of the WHO
      screening algorithm and recommended PT strategy in this population.

PMID- 24327759
TI  - Phase portraits of the proliferation-quiescence decision.
AB  - Mammalian cells make the proliferation or quiescence decision at a specific point
      in the cell cycle called the restriction point, after which they become committed
      to proliferation and independent of growth factors for completion of mitosis. In
      the textbook view, this crucial transition occurs several hours after mitotic
      division (in the middle of G1 phase). In a Cell paper, Spencer et al. show that
      the restriction point should be defined not as a particular time point in G1
      phase but in terms of the ON-OFF status of a bistable switch that emerges from
      the positive feedback in the CDK2-RB-E2F (cyclin-dependent kinase 2
      retinoblastoma-E2F) interaction network. 

PMID- 24327760
TI  - Controlling long-term signaling: receptor dynamics determine attenuation and
      refractory behavior of the TGF-beta pathway.
AB  - Understanding the complex dynamics of growth factor signaling requires both
      mechanistic and kinetic information. Although signaling dynamics have been
      studied for pathways downstream of receptor tyrosine kinases and G protein
      (heterotrimeric guanine nucleotide-binding protein)-coupled receptors, they have
      not been investigated for the transforming growth factor-beta (TGF-beta)
      superfamily pathways. Using an integrative experimental and mathematical modeling
      approach, we dissected the dynamic behavior of the TGF-beta to Smad pathway,
      which is mediated by type I and type II receptor serine/threonine kinases, in
      response to acute, chronic, and repeated ligand stimulations. TGF-beta exposure
      produced a transient response that attenuated over time, resulting in
      desensitized cells that were refractory to further acute stimulation. This loss
      of signaling competence depended on ligand binding, but not on receptor activity,
      and was restored only after the ligand had been depleted. Furthermore, TGF-beta
      binding triggered the rapid depletion of signaling-competent receptors from the
      cell surface, with the type I and type II receptors exhibiting different
      degradation and trafficking kinetics. A computational model of TGF-beta signal
      transduction from the membrane to the nucleus that incorporates our experimental
      findings predicts that autocrine signaling, such as that associated with
      tumorigenesis, severely compromises the TGF-beta response, which we confirmed
      experimentally. Thus, we have shown that the long-term signaling behavior of the
      TGF-beta pathway is determined by receptor dynamics, does not require TGF-beta
      induced gene expression, and influences context-dependent responses in vivo. 

PMID- 24327762
TI  - Accuracy of computed tomography findings in acute pericarditis.
AB  - BACKGROUND: Acute pericarditis is a close clinical mimic of pulmonary embolism
      (PE) in the emergency department, and thus many of these patients are evaluated
      with chest computed tomography (CT). PURPOSE: To study whether CT findings can be
      diagnostic of acute pericarditis. MATERIAL AND METHODS: Using the electronic
      medical record, we retrospectively identified 46 cases of acute pericarditis and
      46 control patients with pericardial effusions due to volume overload, all of
      whom underwent CT examination. Cases were reviewed by two blinded academic
      thoracic radiologists. RESULTS: The majority, 67%, of the pericarditis cases were
      evaluated with PE-protocol CTs. Pericardial thickening/enhancement was the most
      accurate single parameter for pericarditis, with sensitivity of 54-59% and
      specificity of 91-96%. CONCLUSION: CT findings, while not sensitive for
      pericarditis, are diagnostic, with few false-positives. Radiologists should be
      attentive to pericardial thickening or enhancement on CT studies done for chest
      pain, as they may be able to suggest pericarditis as an alternative diagnosis for
      the chest pain.

PMID- 24327761
TI  - Interferon-gamma resets muscle cell fate by stimulating the sequential
      recruitment of JARID2 and PRC2 to promoters to repress myogenesis.
AB  - The inflammatory cytokine interferon-gamma (IFN-gamma) orchestrates a diverse
      array of fundamental physiological processes. IFN-gamma and the class II
      transactivator (CIITA) play essential roles in inhibiting muscle development
      during the inflammatory response. We describe the mechanism through which IFN
      gamma and CIITA inhibit myogenesis by repressing gene expression in muscle cells
      subjected to inflammation. In mice, the presence of increased amounts of
      circulating IFN-gamma resulted in the increased abundance of Polycomb repressive
      complex 2 (PRC2) in muscle fibers, a tissue in which PRC2 is not normally present
      in the adult. We showed that CIITA first interacted with the Jumonji family
      protein JARID2, a noncatalytic subunit of PRC2, which caused an RNA polymerase II
      (RNAPII), phosphorylated at serine-5, to pause at target promoters. Additional
      subunits of the PRC2 complex, including the catalytic subunit EZH2, were then
      recruited in a JARID2-dependent manner that was concurrent with the loss of
      RNAPII and the methylation of Lys(27) of histone H3 (H3K27), which is associated
      with gene repression. IFN-gamma and CIITA act to both promote the abundance of
      PRC2 subunits, which are not normally present during muscle differentation, and
      recruit the PRC2 complex to block myogenesis. Together, these data indicate that
      increased amounts of IFN-gamma reset myogenic cell fate through a multistep
      mechanism that culminates in the recruitment of PRC2 to silence muscle-specific
      genes. 

PMID- 24327763
TI  - Application of the Caprini risk assessment model in evaluation of non-venous
      thromboembolism complications in plastic and reconstructive surgery patients.
AB  - BACKGROUND: The Caprini Risk Assessment Model is used to categorize patient risk
      for venous thromboembolism (VTE) events; its predictive associations have been
      repeatedly corroborated. Calculating scores involves consideration of systemic
      factors that may predict other postoperative complications. OBJECTIVE: This study
      investigates whether Caprini scores can be applied to non-VTE complications.
      METHODS: The authors undertook a retrospective chart review of 1598 encounters
      for a series of complex reconstructive and body contouring operations at an
      academic medical institution. Input variables included Caprini score components,
      patient comorbidities, and prophylactic use of antithrombotic drugs. Output
      variables were postoperative complications. Tests for proportions were performed
      on percentile data. Nonpercentile data were treated with comparison of means (t
      test). Odds ratios for complications were calculated for stratified risk groups
      and compared. RESULTS: The overall complication rate was 28.03%. Deep vein
      thrombosis (DVT) incidence was 1.50%. Differences in age, body mass index (BMI),
      operation time, hypertension, diabetes, renal disease, and cancer were
      statistically significant between patients who experienced complications and
      those who did not. For DVT versus DVT-free patients, differences in sex, BMI,
      operation time, smoking status, diabetes, hypertension, and prior DVT were
      significant. Caprini scores identified 628 encounters as low risk (0-4) and 970
      as high risk (>5). Dehiscence, infection, necrosis, seroma, hematoma, and overall
      complication rate significantly increased the incidence for the high-risk group.
      CONCLUSIONS: Caprini scores can be used as valuable predictors for some non-VTE
      postoperative complications (dehiscence, infection, seroma, hematoma, and
      necrosis). In addition to VTE events, clinicians should pay special attention to
      clinical signs indicative of the complications listed above when dealing with
      high-risk, high-Caprini score patients.

PMID- 24327764
TI  - The effectiveness of facial exercises for facial rejuvenation: a systematic
      review.
AB  - BACKGROUND: Although aesthetic correction of facial aging had long been the
      exclusive domain of plastic surgeons and dermatologists, alternative nonmedical
      approaches to facial rejuvenation are becoming more popular, such as facial
      acupuncture, facial acupressure, and facial exercises. However, the effectiveness
      of these alternative approaches is still a topic of debate. OBJECTIVES: The
      authors review the evidence of the effectiveness of facial exercises for facial
      rejuvenation. METHODS: A literature search was performed in Medline, Web of
      Science, Science Direct, SciELO, and LILACS databases for the terms facial
      rejuvenation, facial exercises, facial massage, face building, face yoga,
      (oro)facial (a)esthetics, (a)esthetic logopedics, and (a)esthetic speech therapy.
      Nine reports were identified from the search and were subject to further
      assessment. RESULTS: Although positive outcomes were achieved in all 9 studies,
      none of the studies used a control group and randomization process. They were
      single case reports, small case series, or studies with a single-group pretest
      posttest design. Moreover, the effectiveness assessments in most of the studies
      were purely subjective, carried out by the authors and/or the patients
      themselves, without blinding. CONCLUSIONS: The evidence to date is insufficient
      to determine whether facial exercises are effective for facial rejuvenation.
      Evidence from large randomized controlled trials will be needed before
      conclusions can be drawn.

PMID- 24327765
TI  - Effects of upstream administration of tirofiban before percutaneous coronary
      intervention on spontaneous reperfusion and clinical outcomes in acute ST-segment
      elevation myocardial infarction.
AB  - We assessed the effects of upstream administration of the glycoprotein IIb/IIIa
      inhibitor tirofiban before percutaneous coronary intervention (PCI) on
      spontaneous reperfusion (SR) of infarct-related artery (IRA) and the clinical
      outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The
      incidence of SR of the IRA was significantly higher in the tirofiban group than
      in the no-tirofiban group (141 [36.5%] vs 21 [17.2%], P < .001). By multivariate
      logistic regression analysis, use of tirofiban (odds ratio 2.32, 95% confidence
      interval 1.25-4.31, P = .008) independently predicted the occurrence of SR.
      Kaplan-Meier survival analysis demonstrated that major adverse cardiovascular
      event-free survival was significantly higher in patients treated with tirofiban
      than in patients without tirofiban at 30-day (log rank = 11.65, P = .001) and 90
      day follow-up (log rank = 16.79, P < .001). Upstream administration of tirofiban
      is significantly associated with increased SR of the IRA and favorable clinical
      prognosis in patients undergoing PCI for STEMI. 

PMID- 24327766
TI  - Mean platelet volume: an emerging diagnostic factor of recurrent aphthous
      stomatitis and behcet disease.

PMID- 24327767
TI  - Endocan in hypertension and cardiovascular disease.

PMID- 24327768
TI  - Estradiol in vivo induces changes in cardiomyocytes size in obese rats.
AB  - We studied the in vivo effects of estradiol on size and biochemical parameters of
      cardiomyocytes in pathophysiological conditions such as obesity and insulin
      resistance. Male Wistar rats were normally fed (controls, n = 7) or fed with high
      fat diet (obese, n = 14). Half of the obese rats (obese + estradiol, n = 7) were
      treated with a single dose of estradiol (40 MUg/kg, intraperitoneally) and 24
      hours after treatment all the rats were killed. Estradiol in vivo in obese rats
      resulted in a significant increase in protein kinase B (Akt) activation (P < .05)
      and decrease in heart mass (P < .05), ratio of the heart mass/body mass (P <
      .05), transverse diameters of cardiomyocytes (P < .001), concentration of serum
      high-sensitivity C-reactive protein (P < .001), and total cholesterol (P < .01)
      compared with obese nontreated rats. Our results suggest that estradiol in
      obese/IR rats affects the size of cardiomyocytes and its actions lead in vivo to
      a reduction in obesity-induced cardiac hypertrophy, via Akt. 

PMID- 24327769
TI  - The etiology of Behcet disease: is it really inflammation or not!

PMID- 24327770
TI  - Serum uric acid concentration and asymptomatic hyperuricemia with subclinical
      organ damage in general population.
AB  - We assessed the effect of increased serum uric acid (SUA) concentration and
      hyperuricemia on subclinical organ damage. A cross-sectional examination of 1243
      asymptomatic patients aged 55 to 84 years was conducted from September to October
      2012. All participants underwent the measurements of SUA and other established
      cardiovascular (CV) risk factors. A morning spot urine sample was collected to
      detect microalbuminuria, and carotid plaque was scanned by B-mode ultrasound; the
      cardioankle vascular index and ankle-brachial index were obtained to evaluate
      arterial stiffness and peripheral artery disease (PAD), respectively. After
      adjustment for established CV risk factors, multiple logistic regression analyses
      showed that the highest quartile of SUA concentration and hyperuricemia had an
      independent association with PAD (respective odds ratios: 3.86 [1.26-11.83] and
      2.33 [1.14-4.77]); this association maintained significantly in males but
      disappeared in females. Serum uric acid concentration and hyperuricemia are
      significantly associated with PAD in males. 

PMID- 24327771
TI  - Practicing What They Preach? Lynching and Religion in the American South, 1890 -
      1929.
AB  - This project employs a moral solidarity framework to explore the relationship
      between organized religion and lynching in the American South. We ask whether a
      county's religious composition impacted its rate of lynching, net of demographic
      and economic controls. We find evidence for the solidarity thesis using three
      religious metrics. First, our findings show that counties with greater religious
      diversity experienced more lynching, supporting the notion that a pluralistic
      religious marketplace with competing religious denominations weakened the bonds
      of a cohesive moral community and might have enhanced white racial solidarity.
      Second, counties in which a larger share of the black population worshipped in
      churches controlled by blacks experienced higher levels of racial violence,
      indicating a threat to the prevailing moral community or inter-group racially
      based solidarity. Finally, we find a lower incidence of lynching in counties
      where a larger share of church members belonged to denominations with racially
      mixed denominations, suggesting that cross-racial solidarity served to reduce
      racial violence.

PMID- 24327772
TI  - Multiscale geometric modeling of macromolecules I: Cartesian representation.
AB  - This paper focuses on the geometric modeling and computational algorithm
      development of biomolecular structures from two data sources: Protein Data Bank
      (PDB) and Electron Microscopy Data Bank (EMDB) in the Eulerian (or Cartesian)
      representation. Molecular surface (MS) contains non-smooth geometric
      singularities, such as cusps, tips and self-intersecting facets, which often lead
      to computational instabilities in molecular simulations, and violate the physical
      principle of surface free energy minimization. Variational multiscale surface
      definitions are proposed based on geometric flows and solvation analysis of
      biomolecular systems. Our approach leads to geometric and potential driven
      Laplace-Beltrami flows for biomolecular surface evolution and formation. The
      resulting surfaces are free of geometric singularities and minimize the total
      free energy of the biomolecular system. High order partial differential equation
      (PDE)-based nonlinear filters are employed for EMDB data processing. We show the
      efficacy of this approach in feature-preserving noise reduction. After the
      construction of protein multiresolution surfaces, we explore the analysis and
      characterization of surface morphology by using a variety of curvature
      definitions. Apart from the classical Gaussian curvature and mean curvature,
      maximum curvature, minimum curvature, shape index, and curvedness are also
      applied to macromolecular surface analysis for the first time. Our curvature
      analysis is uniquely coupled to the analysis of electrostatic surface potential,
      which is a by-product of our variational multiscale solvation models. As an
      expository investigation, we particularly emphasize the numerical algorithms and
      computational protocols for practical applications of the above multiscale
      geometric models. Such information may otherwise be scattered over the vast
      literature on this topic. Based on the curvature and electrostatic analysis from
      our multiresolution surfaces, we introduce a new concept, the polarized
      curvature, for the prediction of protein binding sites.

PMID- 24327773
TI  - Identification of atg8 isoform in encysting Acanthamoeba.
AB  - Autophagy-related protein 8 (Atg8) is an essential component of autophagy
      formation and encystment of cyst-forming parasites, and some protozoa, such as,
      Acanthamoeba, Entamoeba, and Dictyostelium, have been reported to possess a type
      of Atg8. In this study, an isoform of Atg8 was identified and characterized in
      Acanthamoeba castellanii (AcAtg8b). AcAtg8b protein was found to encode 132 amino
      acids and to be longer than AcAtg8 protein, which encoded 117 amino acids. Real
      time PCR analysis showed high expression levels of AcAtg8b and AcAtg8 during
      encystation. Fluorescence microscopy demonstrated that AcAtg8b is involved in the
      formation of the autophagosomal membrane. Chemically synthesized siRNA against
      AcAtg8b reduced the encystation efficiency of Acanthamoeba, confirming that
      AcAtg8b, like AcAtg8, is an essential component of cyst formation in
      Acanthamoeba. Our findings suggest that Acanthamoeba has doubled the number of
      Atg8 gene copies to ensure the successful encystation for survival when 1 copy is
      lost. These 2 types of Atg8 identified in Acanthamoeba provide important
      information regarding autophagy formation, encystation mechanism, and survival of
      primitive, cyst-forming protozoan parasites. 

PMID- 24327774
TI  - A rapid diagnostic test for toxoplasmosis using recombinant antigenic N-terminal
      half of SAG1 linked with intrinsically unstructured domain of gra2 protein.
AB  - Toxoplasma gondii is an apicomplexan parasite with a broad host range of most
      warm-blooded mammals including humans, of which one-thirds of the human
      population has been infected worldwide which can cause congenital defects,
      abortion, and neonatal complications. Here, we developed a rapid diagnostic test
      (RDT) for T. gondii infection. Antigenic N-terminal half of the major surface
      antigen (SAG1) was linked with intrinsically unstructured domain (IUD) of dense
      granule protein 2 (GRA2). The recombinant GST-GRA2-SAG1A protein was successfully
      expressed and purified as 51 kDa of molecular weight. Furthermore, antigenicity
      and solubility of the rGST-GRA2-SAG1A protein were significantly increased. The
      overall specificity and sensitivity of GST-GRA2-SAG1A loaded RDT (TgRDT) were
      estimated as 100% and 97.1% by comparing with ELISA result which uses T. gondii
      whole cell lysates as the antigen. The TgRDT tested with Uganda people sera for
      field trial and showed 31.9% of seroprevalence against T. gondii antibody. The
      TgRDT is proved to be a kit for rapid and easy to use with high accuracy, which
      would be a suitable serodiagnostic tool for toxoplasmosis. 

PMID- 24327775
TI  - Phylogenetic analysis of ruminant Theileria spp. from China based on 28S
      ribosomal RNA gene.
AB  - Species identification using DNA sequences is the basis for DNA taxonomy. In this
      study, we sequenced the ribosomal large-subunit RNA gene sequences (3,037-3,061
      bp) in length of 13 Chinese Theileria stocks that were infective to cattle and
      sheep. The complete 28S rRNA gene is relatively difficult to amplify and its
      conserved region is not important for phylogenetic study. Therefore, we selected
      the D2-D3 region from the complete 28S rRNA sequences for phylogenetic analysis.
      Our analyses of 28S rRNA gene sequences showed that the 28S rRNA was useful as a
      phylogenetic marker for analyzing the relationships among Theileria spp. in
      ruminants. In addition, the D2-D3 region was a short segment that could be used
      instead of the whole 28S rRNA sequence during the phylogenetic analysis of
      Theileria, and it may be an ideal DNA barcode. 

PMID- 24327777
TI  - Comparison of functional gene annotation of Toxascaris leonina and Toxocara canis
      using CLC genomics workbench.
AB  - The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common
      gastrointestinal helminths encountered in dogs. In order to understand biological
      differences of 2 ascarids, we analyzed gene expression profiles of female adults
      of T. canis and T. leonina using CLC Genomics Workbench, and the results were
      compared with those of free-living nematode Caenorhabditis elegans. A total of
      2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively.
      The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820
      bp. Overall, our results showed that most functional gene annotations of 2
      ascarids were quite similar to each other in 3 major categories, i.e., cellular
      component, biological process, and molecular function. Although some different
      transcript expression categories were found, the distance was short and it was
      not enough to explain their different lifestyles. However, we found distinguished
      transcript differences between ascarid parasites and free-living nematodes.
      Understanding evolutionary genetic changes might be helpful for studies of the
      lifestyle and evolution of parasites. 

PMID- 24327776
TI  - Breast-feeding protects infantile diarrhea caused by intestinal protozoan
      infections.
AB  - This study investigated the effect of breast-feeding in protection against
      protozoan infection in infants with persistent diarrhea. Infants were classified
      into 2 groups; 161 breast-fed infants and the same number of non-breast-fed
      infants. Microscopic examinations of stool were done for detection of parasites
      and measuring the intensity of infection. Moreover, serum levels of IgE and TNF
      alpha were measured by ELISA. Cryptosporidium spp., Entamoeba
      histolytica/Entamoeba dispar, Giardia lamblia, and Blastocystis sp. were
      demonstrated in infants with persistent diarrhea. The percentage of protozoan
      infections was significantly lower in breast-fed infants than that in the non
      breast-fed infants. The levels of IgE and TNF-alpha were significantly lower in
      the breast-fed group than in the non-breast-fed group. There were significant
      positive associations between the serum levels of IgE and TNF-alpha and the
      intensity of parasite infection in the breast-fed group. It is suggested that
      breast-feeding has an attenuating effect on the rate and intensity of parasite
      infection. 

PMID- 24327778
TI  - Tetrathyridia of Mesocestoides lineatus in Chinese snakes and their adults
      recovered from experimental animals.
AB  - Morphological characteristics of Mesocestoides lineatus tetrathyridia collected
      from Chinese snakes and their adults recovered from experimental animals were
      studied. The tetrathyridia were detected mainly in the mesentery of 2 snake
      species, Agkistrodon saxatilis (25%) and Elaphe schrenckii (20%). They were 1.73
      by 1.02 mm in average size and had an invaginated scolex with 4 suckers. Adult
      tapeworms were recovered from 2 hamsters and 1 dog, which were orally infected
      with 5-10 larvae each. Adults from hamsters were about 32 cm long and those from
      a dog were about 58 cm long. The scolex was 0.56 mm in average width with 4
      suckers of 0.17 by 0.15 mm in average size. Mature proglottids measured 0.29 by
      0.91 mm (av.). Ovaries and vitellaria bilobed and located in the posterior
      portion of proglottids. The cirrus sac was oval-shaped and located median. Testes
      were follicular, distributed in both lateral fields of proglottids, and 41-52 in
      number per proglottid. Gravid proglottids were 1.84 by 1.39 mm (av.) with a
      characteristic paruterine organ. Eggs were 35 by 27 um in average size with a
      hexacanth embryo. These morphological characteristics of adult worms were
      identical with those of M. lineatus reported previously. Therefore, it has been
      confirmed that the tetrathyridia detected in 2 species of Chinese snakes are the
      metacestodes of M. lineatus, and 2 snake species, A. saxatilis and E. schrenckii,
      play the role of intermediate hosts. 

PMID- 24327779
TI  - Histopathological changes in tissues of Bithynia siamensis goniomphalos incubated
      in crude extracts of camellia seed and mangosteen pericarp.
AB  - The present study was performed to observe histopathological changes in tissues
      of Bithynia siamensis goniomphalos (Gastropoda, Bithyniidae) incubated in crude
      extract solutions of camellia (Camellia oleifera) seed and mangosteen (Garcinia
      mangostana) pericarp, and furthermore to estimate the molluscicidal effects of 2
      plant substances. Substantial numbers of bithyniid snails were incubated in
      various concentrations of 2 plant solution for 24 hr. As the positive control,
      snails incubated in various concentrations of niclosamide, a chemical
      molluscicide, were used. The histopathological findings were observed in
      sectioned snail specimens of each experimental and control groups. The results
      showed that both camellia and mangosteen extracts had molluscicidal effects at 24
      hr with 50% lethal concentration (LC50) at concentrations of 0.003 and 0.002
      g/ml, respectively, while niclosamide had LC50 at concentrations 0.599 ppm. B.
      siamensis goniomphalos snail tissues (foot, gill, and digestive system) showed
      disruption of columnar muscle fibers of the foot, reduction of the length and
      number of gill cilia, numerous mucous vacuoles, and irregularly shaped of
      epithelial cells. Irregular apical and calciferous cells, dilatation of the
      digestive gland tubule, and large hemolymphatic spaces, and irregular apical
      surfaces, detachment of cilia, and enlargement of lysosomal vacuoles of epidermis
      were also shown in all groups. By the present study, it is confirmed that 2
      plants, camellia and mangosteen, are keeping some substance having molluscicidal
      effects, and histopathological findings obtained in this study will provide some
      clues in further studies on their action mechanisms to use them as natural
      molluscicides. 

PMID- 24327780
TI  - An autochthonous case of canine visceral leishmaniasis in Korea.
AB  - A 12-year-old spayed female mixed-bred dog presented with nasal bleeding of 2
      days duration and a skin nodule in the left flank. No abnormalities were found in
      coagulation profiles and blood pressure. Cytological evaluation of the nodule
      revealed numerous characteristic round organisms having a nucleus and a bar
      within macrophages and in the background, consistent with leishmaniasis. In vitro
      culture was unsuccessful but PCR of the nodular aspirate identified the organisms
      as Leishmania infantum, and the final diagnosis was canine leishmaniasis. No
      history of travel to endemic countries was noted. Because the dog had received a
      blood transfusion 2 years before the illness, serological screening tests were
      performed in all donor dogs of the commercial blood bank using the commercial
      Leishmania ELISA test kit, and there were no positive results. Additional 113
      dogs with hyperglobulinemia from Seoul were also screened with the same kits but
      no positive results were obtained. To the best of the author's knowledge this is
      the first autochthonous case of canine leishmaniasis in Korea. 

PMID- 24327781
TI  - A case of vivax malaria complicated by adult respiratory distress syndrome and
      successful management with extracorporeal membrane oxygenation.
AB  - Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly,
      Plasmodium vivax is also being reported as a cause. Since the reemergence of
      indigenous vivax malaria in 1993, cases of severe malaria have been steadily
      reported in Korea. Herein, we report a case of vivax malaria complicated by adult
      respiratory distress syndrome (ARDS) that was successfully managed with
      extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our
      hospital with fever and abdominal pain, which had persisted for 10 days. On
      admission, the patient had impaired consciousness, shock, hypoxia and haziness in
      both lungs, jaundice, thrombocytopenia and disseminated intravascular
      coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood
      smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours
      after admission, hypoxia became more severe, despite providing maximal
      ventilatory support. The administration of antimalarial agents, ECMO, and
      continuous venovenous hemofiltration resulted in an improvement of his vital
      signs and laboratory findings. He was discharged from the hospital 7 weeks later,
      without any sequelae. 

PMID- 24327782
TI  - A case of Plasmodium ovale wallikeri infection in a Chinese worker returning from
      West Africa.
AB  - In contrast to the gradual reduction in the number of locally transmitted malaria
      cases in China, the number of imported malaria cases has been increasing since
      2008. Here, we report a case of a 39-year-old Chinese man who acquired Plasmodium
      ovale wallikeri infection while staying in Ghana, West Africa for 6 months in
      2012. Microscopic examinations of Giemsa-stained thin and thick blood smears
      indicated Plasmodium vivax infection. However, the results of rapid diagnostic
      tests, which were conducted 3 times, were not in agreement with P. vivax. To
      further check the diagnosis, standard PCR analysis of the small-subunit rRNA gene
      was conducted, based on which a phylogeny tree was constructed. The results of
      gene sequencing indicated that this malaria is a variant of P. ovale (P. ovale
      wallikeri). The infection in this patient was not a new infection, but a relapse
      of the infection from the one that he had contracted in West Africa. 

PMID- 24327783
TI  - Molecular diagnosis of an ocular toxocariasis patient in Vietnam.
AB  - An ocular Toxocara canis infection is reported for the first time in Vietnam. A
      34-year-old man residing in a village of Son La Province, North Vietnam, visited
      the National Eye Hospital (NEH) in August 2011. He felt a bulge-sticking pain in
      his left eye and loss of vision occurred over 3 months before visiting the
      hospital. The eye examination in the hospital showed damage of the left eye, red
      eye, retinal fibrosis, retinal detachment, inflammation of the eye tissues,
      retinal granulomas, and a parasitic cyst inside. A larva of Toxocara was
      collected with the cyst by a medical doctor by surgery. Comparison of 264
      nucleotides of internal transcribed spacer 2 (ITS2) of ribosomal DNA was done
      between our Vietnamese Toxocara canis and other Toxocara geographical isolates,
      including Chinese T. canis, Japanese T. canis, Sri Lankan T. canis, and Iranian
      T. canis. The nucleotide homology was 97-99%, when our T. canis was compared with
      geographical isolates. Identification of a T. canis infection in the eye by a
      molecular method was performed for the first time in Vietnam. 

PMID- 24327784
TI  - A case of human pulmonary dirofilariasis in a 48-year-old Korean man.
AB  - Dirofilariasis is a rare disease in humans. We report here a case of a 48-year
      old male who was diagnosed with pulmonary dirofilariasis in Korea. On chest
      radiographs, a coin lesion of 1 cm in diameter was shown. Although it looked like
      a benign inflammatory nodule, malignancy could not be excluded. So, the nodule
      was resected by video-assisted thoracic surgery. Pathologically, chronic
      granulomatous inflammation composed of coagulation necrosis with rim of fibrous
      tissues and granulations was seen. In the center of the necrotic nodules, a
      degenerating parasitic organism was found. The parasite had prominent internal
      cuticular ridges and thick cuticle, a well-developed muscle layer, an intestinal
      tube, and uterine tubules. The parasite was diagnosed as an immature female worm
      of Dirofilaria immitis. This is the second reported case of human pulmonary
      dirofilariasis in Korea. 

PMID- 24327785
TI  - Detection of acute toxoplasmosis in pigs using loop-mediated isothermal
      amplification and quantitative PCR.
AB  - A loop-mediated isothermal amplification (LAMP) assay allows rapid diagnosis of
      Toxoplasma gondii infection. In the present study, the LAMP assay was evaluated
      using blood from both naturally and experimentally infected pigs. The sensitivity
      of the LAMP assay was compared with that of Q-PCR. Both assays detected T. gondii
      in the blood of experimentally infected pigs, with 100% agreement. In infected
      blood samples, the parasite was detected as early as 2 days post-infection and
      reached a peak in 3-5 days. In 216 field serum samples, the detection rates of
      LAMP and Q-PCR assays were 6.9% and 7.8%, respectively. This result indicates
      that the sensitivity of the LAMP assay was slightly lower than that of the Q-PCR
      assay. However, the LAMP may be an attractive diagnostic method in conditions
      where sophisticated and expensive equipment is unavailable. This assay could be a
      powerful supplement to current diagnostic methods. 

PMID- 24327786
TI  - Seroprevalence of Toxoplasma gondii infection in police dogs in Shenyang,
      Northeastern China.
AB  - In recent years, worldwide surveys of Toxoplasma gondii infection in dogs have
      been reported. However, only limited surveys of T. gondii infection in police
      dogs have been available, including China. In the present study, we report the
      seroprevalence of T. gondii in police dogs in Shenyang, northeastern China. Sera
      from 291 police dogs were examined for T. gondii antibodies with the modified
      agglutination test (MAT), and 30.9% animals were tested seropositive. The results
      of the present study indicated a relatively high prevalence of T. gondii
      infection in police dogs in Shenyang, China. 

PMID- 24327787
TI  - Alteration of cytokine production during visceral larva migrans by Toxascaris
      leonina in mice.
AB  - To determine alteration of immune responses during visceral larva migrans (VLM)
      caused by Toxascaris leonina at several time points, we experimentally infected
      mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related
      serial cytokine production after infection. At day 5 post infection (PI), most
      larvae were detected from the lungs, spleen, intestine, and muscle. Expression of
      thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant
      increase in most infected organs, except the intestine. However, expression of
      the CXCL1 (Gro-alpha) gene was most highly enhanced in the intestine at day 14
      PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI,
      and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of
      splenocytes also showed an increase after infection; in particular, IL-5 level
      showed a significant increase at day 14 PI, and the level showed a decrease at
      day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed
      gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related
      cytokine production might be important in immune responses against T. leonina VLM
      in experimental mice. 

PMID- 24327788
TI  - STAT6 expression and IL-13 production in association with goblet cell hyperplasia
      and worm expulsion of Gymnophalloides seoi from C57BL/6 mice.
AB  - In intestinal helminth infections, Th2 immune respones are generally associated
      with mucin secretion for worm expulsion from the host intestine. In particular,
      IL-4 and IL-13 are the important cytokines related with intestinal mucus
      production via STAT6 signalling in nematode infections. However, this perspective
      has never been studied in Gymnophalloides seoi infection. The present study aimed
      to observe the STAT6 signalling and cytokine responses in C57BL/6 mice, a mouse
      strain resistant to infection with this trematode. The results showed that worm
      expulsion occurred actively during days 1-2 post-infection (PI), when goblet
      cells began to proliferate in the small intestine. The STAT6 gene expression in
      the mouse spleen became remarkable from day 2 PI. Moreover, G. seoi infection
      induced a significant increase of IL-13 from day 4 PI in the spleen of infected
      mice. Our results suggested that goblet cell hyperplasia and worm expulsion in G.
      seoi-infected mice should be induced by STAT6 signalling, in which IL-13 may be
      involved as a dominant triggering cytokine. 

PMID- 24327789
TI  - Serological and molecular characteristics of the first Korean case of
      Echinococcus multilocularis.
AB  - In December 2011, we reported an autochthonous case of Echinococcus
      multilocularis infection in a 42-year-old woman in Korea. The diagnosis was based
      on histopathological findings of the surgically resected liver cyst. In the
      present study, we evaluated the serological and molecular characteristics of this
      Korean E. multilocularis case. The patient's serum strongly reacted with affinity
      purified native Em18 and recombinant Em18 antigens (specific for E.
      multilocularis) but negative for recombinant antigen B8/1 (reactive for
      Echinococcus granulosus). In immunoaffinity chromatography, the serum also
      strongly reacted with E. multilocularis and only weakly positive for E.
      granulosus. We determined the whole nucleotide sequence of cox1 (1,608 bp) using
      the paraffin-embedded cystic tissue which was compared with E. multilocularis
      isolates from China, Japan, Kazakhstan, Austria, France, and Slovakia. The Korean
      case showed 99.8-99.9% similarity with isolates from Asia (the highest similarity
      with an isolate from Sichuan, China), whereas the similarity with European
      isolates ranged from 99.5 to 99.6%. 

PMID- 24327790
TI  - Human neurocysticercosis case and an endemic focus of Taenia solium in Lao PDR.
AB  - A male patient with neurocysticercosis was identified in Montai Village, Xay
      District, Oudomxay Province, Lao PDR in February 2004. He had a history of
      diagnosis for neurocysticercosis by a CT scan in Thailand after an onset of
      epileptic seizure in 1993. A pig in the same district was found to contain Taenia
      solium metacestodes (=cysticerci); the slaughtered pig body contained more than
      2,000 cysticerci. In addition to morphological identification, molecular
      identification was also performed on the cysticerci by DNA sequencing analysis of
      the mitochondrial cox1 gene; they were confirmed as T. solium metacestodes. The
      patient is regarded as an indigenous case of neurocysticercosis infected in an
      endemic focus of T. solium taeniasis/cysticercosis in Oudomxay Province, Lao PDR.

PMID- 24327792
TI  - A simple one-pot 2-step N-1-alkylation of indoles with alpha-iminoketones toward
      the expeditious 3-step synthesis of N-1-quinoxaline-indoles.
AB  - A straightforward procedure for the preparation of N-quinoxaline-indoles is
      presented. A base-catalyzed one-pot addition of indoles to a preformed alpha
      iminoketone proceeds on the N-1 indole and the subsequent adduct undergoes an
      acid-mediated deprotection of an internal amino nucleophile, intramolecular
      cyclization and final oxidation generating N-1-quinoxaline-indoles in good yield.

PMID- 24327791
TI  - Intestinal parasites among wild rodents in Northern Gangwon-do, Korea.
AB  - To determine geographical patterns of natural parasite infections among wild
      rodents, a total of 46 wild rodents from 3 different localities in northern
      Gangwon-do (Province), Korea were examined for intestinal parasite infections.
      Along with nematodes such as hookworms and Syphacia spp., Plagiorchis muris (2
      specimens) (Trematoda) were collected from striped field mice, Apodemus agrarius.
      In a Korean wood mouse, Apodemus peninsulae, the overall nematode infections were
      similar to A. agrarius, but an adult worm of Echinostoma hortense (Trematoda) was
      collected. In addition, 2 species of cestodes, i.e., Hymenolepis nana and
      Hymenolepis diminuta, were collected from A. agrarius. Through this survey, A.
      agrarius and A. peninsule were confirmed as the natural definite hosts for
      zoonotic intestinal helminths, i.e., P. muris, E. hortense, H. nana, and H.
      diminuta, in northern Gangwon-do, Korea. Considering increased leisure activities
      around these areas, seasonal and further comprehensive surveys on wild rodents
      seem to be needed to prevent zoonotic parasite infections. 

PMID- 24327793
TI  - Math skills and market and non-market outcomes: Evidence from an Amazonian
      society of forager-farmers.
AB  - Research in industrial nations suggests that formal math skills are associated
      with improvements in market and non-market outcomes. But do these associations
      also hold in a highly autarkic setting with a limited formal labor market? We
      examined this question using observational annual panel data (2008 and 2009) from
      1,121 adults in a native Amazonian society of forager-farmers in Bolivia
      (Tsimane'). Formal math skills were associated with an increase in wealth in
      durable market goods and in total wealth between data collection rounds, and with
      improved indicators of own reported perceived stress and child health. These
      associations did not vary significantly by people's Spanish skills or proximity
      to town. We conclude that the positive association between math skills and market
      and non-market outcomes extends beyond industrial nations to even highly autarkic
      settings.

PMID- 24327797
TI  - Energy Storage via Polyvinylidene Fluoride Dielectric on the Counterelectrode of
      Dye-Sensitized Solar Cells.
AB  - To study the fundamental energy storage mechanism of photovoltaically self
      charging cells (PSCs) without involving light-responsive semiconductor materials
      such as Si powder and ZnO nanowires, we fabricate a two-electrode PSC with the
      dual functions of photocurrent output and energy storage by introducing a PVDF
      film dielectric on the counterelectrode of a dye-sensitized solar cell. A layer
      of ultrathin Au film used as a quasi-electrode establishes a shared interface for
      the I-/I3- redox reaction and for the contact between the electrolyte and the
      dielectric for the energy storage, and prohibits recombination during the
      discharging period because of its discontinuity. PSCs with a 10-nm-thick PVDF
      provide a steady photocurrent output and achieve a light-to-electricity
      conversion efficiency (eta) of 3.38%, and simultaneously offer energy storage
      with a charge density of 1.67 C g-1. Using this quasi-electrode design, optimized
      energy storage structures may be used in PSCs for high energy storage density.

PMID- 24327798
TI  - GM-CSF exhibits anti-inflammatory activity on endothelial cells derived from
      chronic venous disease patients.
AB  - Twenty patients affected by chronic venous disease (CVD) in tertiary venous
      network and/or saphenous vein were analyzed before surgical ablation by echo
      color-doppler for the hemodynamic parameters reflux time (RT) and resistance
      index (RI), a negative and a positive prognostic factor, respectively. RT and RI
      were next correlated with relevant in vitro parameters of venous endothelial
      cells (VEC) obtained from surgical specimens, such as cell migration in response
      to serum gradient, proliferation index, intercellular adhesion molecule (ICAM)-1
      and vascular cell adhesion molecule (VCAM)-1 expression, as well as cytokines
      release. Of interest, ICAM-1 expression in patient-derived VEC cultures
      correlated positively with RT and negatively with RI. Moreover, RT showed a
      positive correlation with the baseline osteoprotegerin (OPG) expression by VEC
      and an inverse correlation with VEC proliferation index. On the other hand, RI
      correlated positively with TNF-related apoptosis inducing ligand (TRAIL)
      expression. Among the cytokines released by VEC, GM-CSF showed a positive
      correlation with VEC proliferation and TRAIL expression and a negative
      correlation with OPG, ICAM-1 and VCAM-1 expression. Since in vitro recombinant GM
      CSF induced VEC proliferation and counteracted the induction of ICAM-1, VCAM-1
      and OPG upon exposure to TNF-alpha, our data suggest an anti-inflammatory
      activity of GM-CSF on venous endothelial cells.

PMID- 24327799
TI  - Differential expression of host biomarkers in saliva and serum samples from
      individuals with suspected pulmonary tuberculosis.
AB  - The diagnosis of tuberculosis remains challenging in individuals with difficulty
      in providing good quality sputum samples such as children. Host biosignatures of
      inflammatory markers may be valuable in such cases, especially if they are based
      on more easily obtainable samples such as saliva. To explore the potential of
      saliva as an alternative sample in tuberculosis diagnostic/biomarker
      investigations, we evaluated the levels of 33 host markers in saliva samples from
      individuals presenting with pulmonary tuberculosis symptoms and compared them to
      those obtained in serum. Of the 38 individuals included in the study,
      tuberculosis disease was confirmed in 11 (28.9%) by sputum culture. In both the
      tuberculosis cases and noncases, the levels of most markers were above the
      minimum detectable limit in both sample types, but there was no consistent
      pattern regarding the ratio of markers in serum/saliva. Fractalkine, IL-17, IL-6,
      IL-9, MIP-1 beta , CRP, VEGF, and IL-5 levels in saliva and IL-6, IL-2, SAP, and
      SAA levels in serum were significantly higher in tuberculosis patients (P <
      0.05). These preliminary data indicate that there are significant differences in
      the levels of host markers expressed in saliva in comparison to those expressed
      in serum and that inflammatory markers in both sample types are potential
      diagnostic candidates for tuberculosis disease. 

PMID- 24327800
TI  - Gene Expression Meta-Analysis Identifies Cytokine Pathways and 5q Aberrations
      Involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer.
AB  - BACKGROUND: Breast tumors have been described by molecular subtypes characterized
      by pervasively different gene expression profiles. The subtypes are associated
      with different clinical parameters and origin of precursor cells. However, the
      biological pathways and chromosomal aberrations that differ between the subgroups
      are less well characterized. The molecular subtypes are associated with different
      risk of metastatic recurrence of the disease. Nevertheless, the performance of
      these overall patterns to predict outcome is far from optimal, suggesting that
      biological mechanisms that extend beyond the subgroups impact metastasis.
      RESULTS: We have scrutinized publicly available gene expression datasets and
      identified molecular subtypes in 1,394 breast tumors with outcome data. By
      analysis of chromosomal regions and pathways using "Gene set enrichment analysis"
      followed by a meta-analysis, we identified comprehensive mechanistic differences
      between the subgroups. Furthermore, the same approach was used to investigate
      mechanisms related to metastasis within the subgroups. A striking finding is that
      the molecular subtypes account for the majority of biological mechanisms
      associated with metastasis. However, some mechanisms, aside from the subtypes,
      were identified in a training set of 1,239 tumors and confirmed by survival
      analysis in two independent validation datasets from the same type of platform
      and consisting of very comparable node-negative patients that did not receive
      adjuvant medical therapy. The results show that high expression of 5q14 genes and
      low levels of TNFR2 pathway genes were associated with poor survival in basal
      like cancers. Furthermore, low expression of 5q33 genes and interleukin-12
      pathway genes were associated with poor outcome exclusively in ERBB2-like tumors.
      CONCLUSION: The identified regions, genes, and pathways may be potential drug
      targets in future individualized treatment strategies.

PMID- 24327801
TI  - Controlling Selectivity for Cycloadditions of Nitrones and Alkenes Tethered by
      Benzimidazoles: Combining Experiment and Theory.
AB  - Herein we describe a combined experimental/theoretical study on the effects of
      substituents on regio- and stereoselectivity in intramolecular 1,3-dipolar
      cycloadditions of nitrones and alkenes tethered by benzimidazoles. By employing a
      large substituent at position R2 or R3, complete selectivity was achieved for
      either the fused or bridged cycloadduct, respectively. In addition, these
      cycloadducts were formed as single diastereomers in all of the cycloadditions
      examined.

PMID- 24327803
TI  - A novel open-loop tracking strategy for photovoltaic systems.
AB  - This paper approaches a dual-axis equatorial tracking system that is used to
      increase the photovoltaic efficiency by maximizing the degree of use of the solar
      radiation. The innovative aspect in the solar tracker design consists in
      considering the tracking mechanism as a perturbation for the DC motors. The goal
      is to control the DC motors, which are perturbed with the motor torques whose
      computation is based on the dynamic model of the mechanical structure on which
      external forces act. The daily and elevation angles of the PV module represent
      the input parameters in the mechanical device, while the outputs transmitted to
      the controller are the motor torques. The controller tuning is approached by a
      parametric optimization process, using design of experiments and response surface
      methodology techniques, in a multiple regression. The simulation and experimental
      results demonstrate the operational performance of the tracking system. 

PMID- 24327802
TI  - Evaluation of different wastewater treatment processes and development of a
      modified attached growth bioreactor as a decentralized approach for small
      communities.
AB  - This study was undertaken to evaluate the potential future use of three
      biological processes in order to designate the most desired solution for on-site
      treatment of wastewater from residential complexes, that is, conventional
      activated sludge process (CASP), moving-bed biofilm reactor (MBBR), and packed
      bed biofilm reactor (PBBR). Hydraulic retention time (HRT) of 6, 3, and 2 h can
      be achieved in CASP, MBBR, and PBBR, respectively. The PBBR dealt with a
      particular arrangement to prevent the restriction of oxygen transfer efficiency
      into the thick biofilms. The laboratory scale result revealed that the overall
      reduction of 87% COD, 92% BOD5, 82% TSS, 79% NH3-N, 43% PO4-P, 95% MPN, and 97%
      TVC at a HRT of 2 h was achieved in PBBR. The microflora present in the system
      was also estimated through the isolation, identification, and immobilization of
      the microorganisms with an index of COD elimination. The number of bacterial
      species examined on the nutrient agar medium was 22 and five bacterial species
      were documented to degrade the organic pollutants by reducing COD by more than
      43%. This study illustrated that the present PBBR with a specific modified
      internal arrangement could be an ideal practice for promoting sustainable
      decentralization and therefore providing a low wastage sludge biomass
      concentration.

PMID- 24327804
TI  - A robust variable sampling time BLDC motor control design based upon MU
      synthesis.
AB  - The variable sampling rate system is encountered in many applications. When the
      speed information is derived from the position marks along the trajectory, one
      would have a speed dependent sampling rate system. The conventional fixed or
      multisampling rate system theory may not work in these cases because the system
      dynamics include the uncertainties which resulted from the variable sampling
      rate. This paper derived a convenient expression for the speed dependent sampling
      rate system. The varying sampling rate effect is then translated into
      multiplicative uncertainties to the system. The design then uses the popular MU
      synthesis process to achieve a robust performance controller design. The
      implementation on a BLDC motor demonstrates the effectiveness of the design
      approach. 

PMID- 24327806
TI  - The relationship between the morphology and structure and the quality of fruits
      of two pear cultivars (Pyrus communis L.) during their development and
      maturation.
AB  - The flavour and nutritional values of pears are appreciated by consumers
      worldwide, who, however, demand specific fruit quality, that is, attractive
      appearance, firmness and flavour, and health safety as well as long-term shelf
      life and storability. Pear cultivars differ in terms of the above-mentioned
      traits; therefore, we undertook investigations to demonstrate the differences in
      structure of fruits of two pear cultivars that determine fruit quality in its
      broadest sense. The micromorphology, anatomy, and ultrastructure of "Clapp's
      Favourite" and "Conference" fruits in the fruit set stage and in the harvest
      maturity stage were investigated under light microscope and scanning and
      transmission electron microscopes. The fruits of "Clapp's Favourite" and
      "Conference" in the fruit set stage exhibited distinct differences in the values
      of anatomical parameters only. Substantial differences in fruit structure were
      observed in the harvest maturity stage. The analyses indicate that firmness and
      durability of pear fruits are largely influenced by the presence of russeting,
      the proportion of closed lenticels and number of stone cells, and the content of
      starch grains and tannin compounds. The thickness of the cuticle and presence of
      epicuticular waxes as well as the number of lenticels and the number and depth of
      microcracks play a minor role. 

PMID- 24327807
TI  - On the accurate identification of network paths having a common bottleneck.
AB  - We present a new mechanism for detecting shared bottlenecks between end-to-end
      paths in a network. Our mechanism, which only needs one-way delays from endpoints
      as an input, is based on the well-known linear algebraic approach: singular value
      decomposition (SVD). Clusters of flows which share a bottleneck are extracted
      from SVD results by applying an outlier detection method. Simulations with
      varying topologies and different network conditions show the high accuracy of our
      technique. 

PMID- 24327805
TI  - AKT kinase pathway: a leading target in cancer research.
AB  - AKT1, a serine/threonine-protein kinase also known as AKT kinase, is involved in
      the regulation of various signalling downstream pathways including metabolism,
      cell proliferation, survival, growth, and angiogenesis. The AKT kinases pathway
      stands among the most important components of cell proliferation mechanism.
      Several approaches have been implemented to design an efficient drug molecule to
      target AKT kinases, although the promising results have not been confirmed. In
      this paper we have documented the detailed molecular insight of AKT kinase
      protein and proposed a probable doxorubicin based approach in inhibiting miR-21
      based cancer cell proliferation. Moreover, the inhibition of miR-21 activation by
      raising the FOXO3A concentration seems promising in reducing miR-21 mediated
      cancer activation in cell. Furthermore, the use of next generation sequencing and
      computational drug design approaches will greatly assist in designing a potent
      drug molecule against the associated cancer cases. 

PMID- 24327808
TI  - Radiological control of the floating mass transducer attached to the round
      window.
AB  - The surgical rehabilitation of mixed hearing losses can be performed by coupling
      the floating mass transducer of the Vibrant Soundbridge to the round window. The
      quality of coupling the floating mass transducer to the round window is crucial
      for the audiological outcome. It was the aim of this study to further observe the
      different patterns of floating mass transducer position at the round window. We
      compared twenty patients with mixed hearing loss implanted with a floating mass
      transducer attached to the round window and 24 surgeries between 5/2007 and
      6/2010. An evaluation of the chronological observation of the flat panel
      angiography-controlled position of the floating mass transducer at the round
      window with relation to the surgical report and the audiological outcome was
      done. We observed no changes in the mean pre- and postbone conduction thresholds.
      The floating mass transducer position was variable and could be radiologically
      classified and correlated with the audiologically outcome. A learning curve was
      observed from the earlier to later implantations. Postoperative, radiological
      evaluation of the location and angle of the floating mass transducer by means of
      flat panel tomography allowed us to classify the floating mass transducer
      position at the round window into 4 groups. 

PMID- 24327809
TI  - Thin film heater for removable volatile protecting coatings.
AB  - Freshly coated aluminum mirrors have excellent reflectivity at far ultraviolet
      wavelengths. However, reflectivity rapidly degrades when the mirror surfaces are
      exposed to atmosphere. In order to avoid this problem, freshly coated aluminum
      surface can be protected by over-coating of a removable volatile protecting
      coating. This protecting coating can be re-evaporated by controlled heating or by
      some other methods when required. This type of removable coating has immediate
      application in UV space astronomy. The purpose of this paper is to demonstrate
      the feasibility of re-evaporation of removable volatile Zn protecting coating
      using a NiCr thin film heater without affecting the reflection properties of Al
      mirror surfaces. 

PMID- 24327810
TI  - Induction of a Soluble Anti-HIV-1 factor (s) with IFN-gamma, IL-10, and beta
      Chemokine Modulating Activity by an Influenza-Bacterial Polyantigenic Mixture.
AB  - Partial immune restoration may be obtained with highly active antiretroviral
      therapy (HAART), but specific anti-HIV-1 immune responses do not appear to
      improve substantially. We have demonstrated that a soluble factor(s) induced by a
      mixture of inactivated influenza and bacterial vaccines called polyantigenic
      immunomodulator (PAI), possesses strong immunoregulatory and anti-HIV-1
      activities. In the present study, we show that culture fluids from both PAI
      stimulated peripheral blood mononuclear cells (PBMC) and CD8+ T-cells of HIV-1
      infected patients were able to suppress HIV-1 replication in an MHC-unrestricted
      fashion. The PAI-induced antiviral activity was eliminated when culture fluids
      were pre-heated at 100 degrees C for 10 min. and it is associated with induction
      of IFN-gamma, MIP-1alpha, MIP-1beta, and RANTES production, but inhibition of IL
      10. Furthermore, this induction is dependent on the immunological status (CD4:CD8
      ratio) of the HIV-1 infected patient. Taken together, our results suggest that
      the MHC-unrestricted HIV-1 suppression that is induced by culture fluids from PAI
      stimulated PBMC may result from the stimulation of immune cell subpopulations to
      produce a heat-labile antiviral soluble factor(s), which in turn modulate
      cytokine and beta-chemokine production. The identification of this PAI-induced
      soluble factor(s) may have major therapeutic potential.

PMID- 24327811
TI  - Monogamy on the Street: A Mixed-Methods Study of Homeless Men.

PMID- 24327812
TI  - Takotsubo cardiomyopathy as an early complication of drug-induced suicide
      attempt.
AB  - Takotsubo cardiomyopathy typically presents in menopausal women following
      episodes of intense physical or mental stress. To our knowledge, the literature
      contains only two documented cases of Takotsubo cardiomyopathy arising following
      a suicide attempt, neither of which involved pharmaceutical poisoning. Here,
      however, we document the case of a young male patient with borderline personality
      disorder and a clinical and angiographic presentation compatible with Takotsubo
      cardiomyopathy arising following a suicide attempt by voluntary drug intoxication
      (risperidone, barbiturates, and benzodiazepine). The potential pathophysiological
      mechanisms behind this unusual clinical picture are discussed. 

PMID- 24327813
TI  - Effect of 808nm diode laser irradiation on root canal walls after smear layer
      removal: A scanning electron microscope study.
AB  - INTRODUCTION: This study was carried out to investigate the effect of 808nm diode
      laser irradiation on dentinal tubules of root canal wall. MATERIALS AND METHODS:
      Twelve single-rooted teeth were used. After cleaning and shaping with rotary
      instruments by the crown down technique, the smear layer was removed by
      alternating irrigation with EDTA and sodium hypochlorite. The teeth were then
      randomly divided into experimental and control groups of six teeth each. In
      experimental group, laser irradiation was activated inside the canal and the
      teeth of the other group served as controls. Kruskal-Wallis and Friedman tests
      were used for comparing occluded dentinal tubules in different part of the roots.
      RESULTS: Scanning electron microscopy showed that occluded dentinal tubules could
      be observed in all laser irradiated teeth; however, none of the control teeth
      showed occluded dentinal tubules. The Friedman test showed that in the laser
      irradiated group the best result was achieved in the apical third of the root
      canals compared with the middle (p<0.005) and cervical third (p<0.002). Dentinal
      tubules of the middle third were also significantly different from the cervical
      third as well (p<0.005). CONCLUSION: Laser radiation after removing smear layer
      could successfully occlude dentinal tubules and the best results was achieved at
      the apical part of the canal.

PMID- 24327814
TI  - An Evaluation of the Sealing Ability of MTA and Resilon: A Bacterial Leakage
      Study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the sealing ability of
      gray-colored mineral trioxide aggregate (GMTA), white-colored MTA (WMTA), and
      Resilon as root filling materials. MATERIALS AND METHODS: Sixty-six human
      maxillary central incisors were used in the present study. In the group A, 20
      teeth were filled with GMTA. In the group B, 20 teeth were filled with WMTA and
      in the group C, 20 teeth were filled with Resilon/Epiphany. Three teeth were used
      as positive (obturated using the single gutta-percha cone technique without
      sealer) and three were used as negative (obturated with gutta-percha and AH-26
      sealer, coated with two layers of nail varnish) controls. A bacterial leakage
      model utilizing Enterococcus faecalis was used for evaluation. Leakage was noted
      when turbidity was observed. RESULTS: Controls behaved as expected. In the group
      A (GMTA) three samples, in the group B (WMTA) four samples, and in the group C
      (Resilon/Epiphany), two samples were leaked. There was no statistically
      significant difference between GMTA and WMTA or GMTA and Resilon. CONCLUSION: In
      conclusion, sealing ability of GMTA and WMTA was similar to Resilon as orthograde
      root filling materials.

PMID- 24327815
TI  - Finite element evaluation of stress distribution in mature and immature teeth.
AB  - INTRODUCTION: Traumatic injuries may affect the vitality and development of
      tooth. So divergence or parallelism of canal walls induces an open apex which is
      very susceptible to fracture. The aim of this study was to determine the stress
      distribution pattern in immature teeth and compare it with mature teeth.
      MATERIALS AND METHODS: In order to analyze stress distribution using finite
      element method, models were first designed according to actual samples by "ANSYS"
      software. Two models of the maxillary central incisors were designed, one mature
      and one with open apex. Mature tooth was designed as having undergone root canal
      therapy with gutta-percha and the immature one with both MTA plug and gutta
      percha. Samples were loaded in seven stages and then, the stress distribution in
      each model was measured, using the "ANSYS" software. RESULTS: During gutta-percha
      condensation, the immature tooth transfers the stress directly to the external
      root surface where force is directly applied, whereas during masticatory occlusal
      forces, the stress is transferred to middle third of buccal and lingual surfaces
      and to buccal cervix in lunar shape. During traumatic forces, stress
      concentration was on the cervical region of buccal surface and middle third of
      buccal and lingual surfaces. MTA plug prevents stress distribution toward apical
      region and forces concentrate in dentin at the point where stress terminates.
      CONCLUSION: Within the limitations of this simulated mechanical analysis, it was
      confirmed that the pattern of stress distribution in mature and immature teeth is
      different. Cervical area of the buccal surface in immature teeth is one of the
      stress concentration areas, which contribute to the high rate of fracture in this
      area.

PMID- 24327816
TI  - Histologic Evaluation of Three Treatment Methods for Direct Pulp Capping of Cat's
      Canine.
AB  - INTRODUCTION: Direct pulp capping (DPC) is coverage of exposed pulp by a
      biocompatible material after traumatic or carious exposure. The purpose of this
      procedure is to seal against bacterial leakage, stimulate dentinal barrier
      formation, and maintain the vitality of pulp. Several factors contribute to the
      consequence of this treatment such as material and the procedural technique. The
      aim of this study was to histological evaluation of three treatment methods
      (Laser+MTA, Laser+Ca(OH)2 and MTA alone) in direct pulp capping of cat's canines.
      MATERIALS AND METHODS: Thirty six canine teeth of 9 cats were selected for this
      experimental study. After anesthesia, the teeth were exposed under isolated
      condition. The teeth were randomly divided into three treatment groups. In group
      I, the pulp exposures were covered by Mineral Trioxide Aggregate (MTA) alone. In
      group II, the pulps after treating with Er: YAG laser, were covered by MTA. In
      group III, treating with laser and covering with Ca(OH)2 was performed. All
      cavities were filled by Amalgam after DPC. After 4 months, the animals were
      sacrificed and block sections were prepared. Then, the specimens were
      histologically evaluated according to the scores that designed by a pathologist.
      The data was analyzed by Mann-Whitney and Chi-square tests with significant level
      of 95%. RESULTS: Dentinal barrier was formed in all groups. Laser+MTA group
      showed nearly similar results to other groups in dentinal barrier formation, type
      and intensity of inflammatory responses and soft tissue changes (P>0.05).
      CONCLUSION: Although Laser+MTA had slightly better effects, but this difference
      was not statistically significant. Based on this study, it seems that laser
      treatment has no effect on outcome of DPC.

PMID- 24327817
TI  - Tissue dissolving ability of several endodontic irrigants on bovine pulp tissue.
AB  - INTRODUCTION: A desirable characteristic of root canal irrigants is the ability
      of dissolving soft tissues. Sodium hypochlorite, an antibacterial and tissue
      solvent irrigant used in endodontic treatment is known to be toxic for periapical
      tissues. Chlorhexidine gluconate, an effective antimicrobial agent, is another
      irrigant with limited tissue dissolving ability. A mixture of a tetracycline
      isomer, an acid, and a detergent (MTAD), has recently been introduced as an
      alternative irrigant in root canal therapy. The purpose of this study was to
      evaluate the tissue dissolving effect of these root canal irrigants on bovine
      pulp tissue. MATERIALS AND METHODS: Fifty pieces of bovine pulp tissue 80 mg each
      were treated with either normal saline, MTAD, 2% chlorhexidine gluconate, 2.6%
      NaOCl or 5.25% NaOCl for 10 min at 37 degrees C. Desiccated pre-treatment and
      post-treatment weights of samples were compared. Using Kruskal-Wallis and Mann
      Whitney U tests, data was analyzed. RESULTS: Tissue dissolution effect of 5.25%
      NaOCl (85.98%) was statistically greater than that of all other solutions
      (P<0.05). Chlorhexidine gluconate had the weakest dissolution effect, and
      dissolved only 9.36% of the sample tissue. No significant differences were
      observed between the dissolution effects of normal saline or MTAD. CONCLUSION:
      Based on the results of this study, the use of NaOCl as intracanal irrigation
      during instrumentation is recommended, because of its greater tissue dissolution
      effect.

PMID- 24327818
TI  - Evaluation of the success rate of nonsurgical single visit retreatment.
AB  - INTRODUCTION: Advantages of endodontic treatments over tooth extraction have
      increased the demands for these treatments. Success rate of these treatments is
      generally lower than the primary root canal therapies. Recently, single visit
      treatments have gained more popularity. But, the influence of completing
      retreatment in a single appointment on success of the treatment is still a
      controversy. The aim of this study was evaluating the most common causes of
      failures and determining the success rate of completing retreatments in single
      appointment. MATERIALS AND METHODS: Hundred and twenty four patients who had
      single appointment retreatment within past 4 years in postgraduate ward of Shahid
      Beheshti Dental School were selected and clinical and radiographic examinations
      were carried out. The data were analyzed by SPSS using Chi-square and Exact
      Fisher tests. RESULTS: Success rate and uncertain cases were shown to be 50.7%
      and 34.2%, respectively and failure rate was 15.1%. Presence of periradicular
      lesion or history of swelling prior to retreatment had significant effect on the
      success of single visit retreatments (p<0.001). Another important finding of the
      study was that the success rate of retreatments was significantly higher in cases
      referred for restorative purposes compared with retreatments for nonrestorative
      purposes (p<0.001). CONCLUSION: The overall success rate of single appointment
      retreatments is up to 84.9% which is considerably higher in cases referred for
      restorative purposes. So based on the results of this study single appointment
      retreatment of symptom less teeth is recommended.

PMID- 24327819
TI  - Endodontic treatment of a maxillary second molar with developmental anomaly: a
      case report.
AB  - Fusion is a rare occurrence in molar teeth. The purpose of this rare case
      presentation is to describe the nonsurgical endodontic treatment of maxillary
      molar. A 28-year-old patient was referred for endodontic treatment of her chronic
      apical abscess of right maxillary second molar. In the clinical examination, a
      sinus tract adjacent to involved tooth and a small crown of supernumerary tooth
      fused to the buccal surface of the molar at gingival margin was observed.
      Endodontic treatment was decided for the involved molar for functional reason.
      Recall examination, a year after completion of endodontic and restorative
      treatments, showed the tooth was clinically asymptomatic and there was no
      radiographic lucency around the apical region. 

PMID- 24327820
TI  - Comparison of physical therapy with energy healing for improving range of motion
      in subjects with restricted shoulder mobility.
AB  - Two forms of energy healing, Reconnective Healing (RH) and Reiki, which involve
      light or no touch, were tested for efficacy against physical therapy (PT) for
      increasing limited range of motion (ROM) of arm elevation in the scapular plane.
      Participants were assigned to one of 5 groups: PT, Reiki, RH, Sham Healing, or no
      treatment. Except for no treatment, participants were blinded as to grouping.
      Range of Motion, self-reported pain, and heart rate variability (HRV) were
      assessed before and after a 10-minute session. On average, for PT, Reiki, RH,
      Sham Healing, and no treatment, respectively, ROM increased by 12 degrees , 20
      degrees , 26 degrees , 0.6 degrees , and 3 degrees  and pain score decreased by
      11.5%, 10.1%, 23.9%, 15.4%, and 0%. Physical therapy, Reiki, and RH were more
      effective than Sham Healing for increasing ROM (PT: F = 8.05, P = 0.008; Reiki: F
      = 10.48, P = 0.003; RH: F = 30.19, P < 0.001). It is possible that this
      improvement was not mediated by myofascial release because the subjects' HRV did
      not change, suggesting no significant increase in vagal activity. Sham treatment
      significantly reduced pain compared to no treatment (F = 8.4, P = 0.007) and was
      just as effective as PT, Reiki, and RH. It is the authors' opinion that the
      accompanying pain relief is a placebo effect. 

PMID- 24327822
TI  - The infrared radiation temperature characteristic of acupoints of mammary gland
      hyperplasia patients.
AB  - Objective. To ascertain pathological information on hyperplasia of mammary glands
      (HMG) of patients via the infrared radiation temperature of acupoints. Method.
      Patients with HMG and healthy controls were tested using an infrared thermal
      imager. Results. In controls, no significant difference in temperature was
      observed between points with the same name (P > 0.05). The temperature of all
      tested points was found to be higher in the group with HMG than in that of the
      healthy controls, except for the left and right Zusanli (ST36). The temperature
      of the right Rugen (ST18), Guanyuan (CV4), Qihai (CV6), and Hegu (LI4) reached a
      statistically significant heightened level (P = 0.046~P < 0.001). The temperature
      of the Zusanli (ST36) and Hegu (LI4) present on the right side was significantly
      higher than that of the left (P = 0.001 and P = 0.004, resp.), while the
      temperature of the left Youmen (KI21) was significantly higher than that of the
      right (P = 0.008). Conclusion. The temperature of the bilateral acupoints in
      healthy controls was symmetrical, and the raised temperatures observed of the
      Rugen (ST18), Guanyuan (CV4), Qihai (CV6), and Hegu (LI4) acupoints of HMG
      patients and the imbalance of the temperature of the bilateral acupoints Zusanli
      (ST36), Youmen (KI21), and Hegu (LI4) carried special pathological information
      about HMG disease. 

PMID- 24327821
TI  - The Protective Role of Resveratrol against Arsenic Trioxide-Induced
      Cardiotoxicity.
AB  - Arsenic trioxide (As2O3) shows substantial anticancer activity in patients with
      acute promyelocytic leukemia (APL). Unfortunately, limiting the application of
      this effective agent to APL patients is severe cardiotoxicity. Resveratrol, the
      natural food-derived polyphenolic compound, is well known for its antioxidant
      properties and protects the cardiovascular system. But the potential role of
      resveratrol against As2O3 in heart via nuclear factor erythroid 2-related factor
      2 (Nrf2) and heme oxygenase-1 (HO-1) is unclear. The present study evaluated the
      effects of pretreatment with resveratrol and As2O3 on oxidative stress and
      cardiac dysfunction in rat. In the present study, resveratrol decreased As2O3
      induced reactive oxygen species generation, oxidative DNA damage, and
      pathological alterations. In addition, cardiac dysfunction parameters,
      intracellular calcium and arsenic accumulation, glutathione redox ratio, and cAMP
      deficiency levels were observed in As2O3-treated rats; these changes were
      attenuated by resveratrol. Furthermore, resveratrol significantly prohibited the
      downregulation of both Nrf2 and HO-1 gene expressions that were downregulated by
      As2O3, whereas resveratrol did not alter As2O3-induced nitric oxide formation.
      Thus, the protective role of resveratrol against As2O3-induced cardiotoxicity is
      implemented by the maintenance of redox homeostasis (Nrf2-HO-1 pathway) and
      facilitating arsenic efflux. Our findings suggest coadministration with
      resveratrol, and As2O3 might provide a novel therapeutic strategy for APL. 

PMID- 24327823
TI  - Erratum: Drug-primed reinstatement of cocaine seeking in mice: increased
      excitability of mediumsized spiny neurons in the nucleus accumbens.
AB  - [This corrects the article on p. e122 in vol. 5.].

PMID- 24327824
TI  - ESTIMATING DAILY NITROGEN DIOXIDE LEVEL: EXPLORING TRAFFIC EFFECTS.
AB  - Data used to assess acute health effects from air pollution typically have good
      temporal but poor spatial resolution or the opposite. A modified longitudinal
      model was developed that sought to improve resolution in both domains by bringing
      together data from three sources to estimate daily levels of nitrogen dioxide
      (NO2) at a geographic location. Monthly NO2 measurements at 316 sites were made
      available by the Study of Traffic, Air quality and Respiratory health (STAR).
      Four US Environmental Protection Agency monitoring stations have hourly
      measurements of NO2. Finally, the Connecticut Department of Transportation
      provides data on traffic density on major roadways, a primary contributor to NO2
      pollution. Inclusion of a traffic variable improved performance of the model, and
      it provides a method for estimating exposure at points that do not have direct
      measurements of the outcome. This approach can be used to estimate daily
      variation in levels of NO2 over a region.

PMID- 24327825
TI  - Steviol glycosides modulate glucose transport in different cell types.
AB  - Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South
      America, have been used as a sweetener since ancient times. Currently, Stevia
      extracts are largely used as a noncaloric high-potency biosweetener alternative
      to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and
      metabolic disorders worldwide. Despite the large number of studies on Stevia and
      steviol glycosides in vivo, little is reported concerning the cellular and
      molecular mechanisms underpinning the beneficial effects on human health. The
      effect of four commercial Stevia extracts on glucose transport activity was
      evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The
      extracts were able to enhance glucose uptake in both cellular lines, as
      efficiently as insulin. Our data suggest that steviol glycosides could act by
      modulating GLUT translocation through the PI3K/Akt pathway since treatments with
      both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt.
      Furthermore, Stevia extracts were able to revert the effect of the reduction of
      glucose uptake caused by methylglyoxal, an inhibitor of the insulin
      receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia
      extracts could mimic insulin effects modulating PI3K/Akt pathway. 

PMID- 24327827
TI  - Antioxidants in longevity and medicine.

PMID- 24327826
TI  - Hypothermia improves oral and gastric mucosal microvascular oxygenation during
      hemorrhagic shock in dogs.
AB  - Hypothermia is known to improve tissue function in different organs during
      physiological and pathological conditions. The aim of this study was to evaluate
      the effects of hypothermia on oral and gastric mucosal microvascular oxygenation
      (MUHbO2) and perfusion (MUflow) under physiological and hemorrhagic conditions.
      Five dogs were repeatedly anesthetized. All animals underwent each experimental
      protocol (randomized cross-over design): hypothermia (34 degrees C), hypothermia
      during hemorrhage, normothermia, and normothermia during hemorrhage.
      Microcirculatory and hemodynamic variables were recorded. Systemic (DO2) and oral
      mucosal (MUDO2) oxygen delivery were calculated. Hypothermia increased oral MU
      HbO2 with no effect on gastric MUHbO2. Hemorrhage reduced oral and gastric MUHbO2
      during normothermia (-36 +/- 4% and -27 +/- 7%); however, this effect was
      attenuated during additional hypothermia (-15 +/- 5% and -11 +/- 5%). The
      improved MU HbO2 might be based on an attenuated reduction in MU flow during
      hemorrhage and additional hypothermia (-51 +/- 21 aU) compared to hemorrhage and
      normothermia (-106 +/- 19 aU). MUDO2 was accordingly attenuated under hypothermia
      during hemorrhage whereas DO2 did not change. Thus, in this study hypothermia
      alone improves oral MUHbO2 and attenuates the effects of hemorrhage on oral and
      gastric MU HbO2. This effect seems to be mediated by an increased MUDO2 on the
      basis of increased MU flow.

PMID- 24327828
TI  - Self-Assembly and Thermal Stability of Binary Superlattices of Gold and Silicon
      Nanocrystals.
AB  - Simple hexagonal (sh) AB2 binary superlattices (BSLs) of organic ligand-capped
      silicon (A; 5.40(+/-9.8%) nm diameter) and gold (B; 1.88(+/-10.1%) nm diameter)
      nanocrystals were assembled by evaporation of colloidal dispersions and
      characterized using transmission electron microscopy (TEM) and grazing incidence
      small-angle X-ray scattering (GISAXS). When deposited on tilted substrates by
      slow evaporation, the sh-AB2 superlattice contracts slightly towards the
      substrate with centered orthorhombic structure. Heating the BSL to 200 degrees C
      in air led to gold coalescence and segregation to the surface of the assembly
      without disrupting the Si nanocrystal sublattice, thus creating a simple
      hexagonal superlattice of Si nanocrystals.

PMID- 24327829
TI  - Formal Anti-Markovnikov Hydroamination of Terminal Olefins.
AB  - A new strategy to access linear amines from terminal olefin precursors is
      reported. This two-step, one-pot hydroamination methodology employs sequential
      oxidation and reduction catalytic cycles. The formal hydroamination
      transformation proceeds with excellent regioselectivity, and only the anti
      Markovnikov product is observed. Up to 70% yield can be obtained from styrenes or
      aliphatic olefins and either primary or secondary aromatic amines. Additionally,
      the scope is broad with respect to the olefin and accommodates a variety of
      functionalities; we demonstrate that amines with removable aryl protecting groups
      may be utilized to allow access to a more diverse array of hydroamination
      adducts.

PMID- 24327874
TI  - Mobile phones affect multiple sperm quality traits: a meta-analysis.
AB  - As mobile phone usage is growing rapidly, there is a need for a comprehensive
      analysis of the literature to inform scientific debates about the adverse effects
      of mobile phone radiation on sperm quality traits. Therefore, we conducted a meta
      analysis of the eligible published research studies on human males of
      reproductive age. Eleven studies were eligible for this analysis. Based on the
      meta-analysis, mobile phone use was significantly associated with deterioration
      in semen quality (Hedges's g = -0.547; 95% CI: -0.713, -0.382; p < 0.001). The
      traits particularly affected adversely were sperm concentration, sperm
      morphology, sperm motility, proportion of non-progressive motile sperm (%),
      proportion of slow progressive motile sperm (%), and sperm viability. Direct
      exposure of spermatozoa to mobile phone radiation with in vitro study designs
      also significantly deteriorated the sperm quality (Hedges's g = -2.233; 95% CI: 
      2.758, -1.708; p < 0.001), by reducing straight line velocity, fast progressive
      motility, Hypo-osmotic swelling (HOS) test score, major axis (um), minor axis
      (um), total sperm motility, perimeter (um), area (um 2), average path velocity,
      curvilinear velocity, motile spermatozoa, and  acrosome reacted spermatozoa (%).
      The strength of evidence for the different outcomes varied from very low to very
      high. The analysis shows that mobile phone use is possibly associated with a
      number of deleterious effects on the spermatozoa.

PMID- 24327864
TI  - Advances in systemic therapy for advanced pancreatobiliary malignancies.
AB  - Pancreatobiliary malignancies are relatively uncommon and the overall prognosis
      is poor. Treatment options for advanced disease are limited to systemic therapy
      for metastatic disease and a combination of systemic therapy and radiation
      therapy for locally advanced but unresectable tumors. There have been significant
      advances in the treatment of pancreatobiliary cancers in recent years but the
      prognosis for patient survival remains disappointingly poor. We review the
      current treatment options for locally advanced pancreatobiliary malignancies and
      highlight recent advances in systemic therapy, including novel approaches using
      targeted treatments.

PMID- 24327877
TI  - Is gastroenterology research in decline? A comparison of abstract publication
      rates from The British Society of Gastroenterology meetings between 1995 and
      2005.
AB  - Background: Reports have suggested that academic medicine may be in decline
      within the UK. Further evidence suggests that rates of subsequent full
      publication of abstracts presented at major scientific meetings are low and may
      be declining. We have compared the publication rates of abstracts presented at
      meetings of the British Society of Gastroenterology (BSG) between 1995 and 2005
      and examined factors associated with full paper publication.  Methods: Abstracts
      presented at BSG meetings in 1995 and 2005 were assessed by cross-referencing
      with multiple databases. Abstract characteristics associated with publication
      were analysed. Results: There were no differences in overall publication rates,
      impact factors or time to publication between 1995 and 2005. Overall, basic
      science abstracts were twice as likely to achieve full publication than non-basic
      science. There was a significant fall in the publication rates for case series
      and audits, and significantly increased rates for fundamental/basic-science
      abstracts over the study period. There were non-significant increases in
      publication rates for controlled trials and systematic reviews. In general,
      publication rates for all predominantly clinically orientated abstracts reduced
      between the two periods with the most notable fall occurring in nutrition. 
      Conclusions: There was no evidence of a decline in overall abstract publication
      rates between 1995 and 2005. There seemed to be trend for increased publication
      rates of abstracts using perceived high-quality study methodologies with a
      corresponding decrease in those with lower quality methods. The proportion of
      basic-science abstracts is likely to be a determinant of overall full publication
      rates following scientific meetings.

PMID- 24327840
TI  - Neuronal activity-regulated gene transcription: how are distant synaptic signals
      conveyed to the nucleus?
AB  - Synaptic activity can trigger gene expression programs that are required for the
      stable change of neuronal properties, a process that is essential for learning
      and memory. Currently, it is still unclear how the stimulation of dendritic
      synapses can be coupled to transcription in the nucleus in a timely way given
      that large distances can separate these two cellular compartments. Although
      several mechanisms have been proposed to explain long distance communication
      between synapses and the nucleus, the possible co-existence of these models and
      their relevance in physiological conditions remain elusive. One model suggests
      that synaptic activation triggers the translocation to the nucleus of certain
      transcription regulators localised at postsynaptic sites that function as synapto
      nuclear messengers. Alternatively, it has been hypothesised that synaptic
      activity initiates propagating regenerative intracellular calcium waves that
      spread through dendrites into the nucleus where nuclear transcription machinery
      is thereby regulated. It has also been postulated that membrane depolarisation of
      voltage-gated calcium channels on the somatic membrane is sufficient to increase
      intracellular calcium concentration and activate transcription without the need
      for transported signals from distant synapses. Here I provide a critical overview
      of the suggested mechanisms for coupling synaptic stimulation to transcription,
      the underlying assumptions behind them and their plausible physiological
      significance.

PMID- 24327878
TI  - Critical care management of patients following transcatheter aortic valve
      replacement.
AB  - Transcatheter aortic valve replacement (TAVR) is rapidly gaining popularity as a
      technique to surgically manage aortic stenosis (AS) in high risk patients. TAVR
      is significantly less invasive than the traditional approach to aortic valve
      replacement via median sternotomy. Patients undergoing TAVR often suffer from
      multiple comorbidities, and their postoperative course may be complicated by a
      unique set of complications that may become evident in the intensive care unit
      (ICU). In this article, we review the common complications of TAVR that may be
      observed in the ICU, and different strategies for their management.

PMID- 24327885
TI  - Assets of the non-pathogenic microorganism Dictyostelium discoideum as a model
      for the study of eukaryotic extracellular vesicles.
AB  - Dictyostelium discoideum microvesicles have recently been presented as a valuable
      model for eukaryotic extracellular vesicles. Here, the advantages of D.
      discoideum for unraveling important biological functions of extracellular
      vesicles in general are detailed. D. discoideum, a non-pathogenic eukaryotic
      microorganism, belongs to a billion-year-old Amoeboza lineage, which diverged
      from the animal-fungal lineage after the plant animal-split. During growth and
      early starvation-induced development, it presents analogies with lymphocytes and
      macrophages with regard to motility and phagocytosis capability, respectively.
      Its 6-chromosome genome codes for about 12,500 genes, some showing analogies with
      human genes. The presence of extracellular vesicles during cell growth has been
      evidenced as a detoxification mechanism of various structurally unrelated drugs.
      Controls led to the discovery of constitutive extracellular vesicle secretion in
      this microorganism, which was an important point. It means that the secretion of
      extracellular vesicles occurs, in the absence of any drug, during both cell
      growth and early development. This constitutive secretion of D. discoideum cells
      is very likely to play a role in intercellular communication. The detoxifying
      secreted vesicles, which can transport drugs outside the cells, can also act as
      "Trojan horses", capable of transferring these drugs not only into naive D.
      discoideum cells, but into human cells as well. Therefore, these extracellular
      vesicles were proposed as a new biological drug delivery tool. Moreover,
      Dictyostelium, chosen by the NIH (USA) as a new model organism for biomedical
      research, has already been used for studying some human diseases. These cells,
      which are much easier to manipulate than human cells, can be easily designed in
      simple conditioned medium experiments. Owing to the increasing consensus that
      extracellular vesicles are probably important mediators of intercellular
      communication, D. discoideum is here suggested to constitute a convenient model
      for tracking as yet unknown biological functions of eukaryotic extracellular
      vesicles.

PMID- 24327918
TI  - The effects of anaesthesia on the developing brain: a summary of the clinical
      evidence.
AB  - Introduction: There is data amassing in the literature regarding the potentially
      adverse effects of anaesthesia exposure on the developing human brain. The
      purpose of this article is to summarise current relevant data from clinical
      studies in this area. Methods: Articles from journals written in English were
      searched for using PubMed, Ovid and Medline. Keywords used included: brain
      (newborn, infant, child and neonate), neurodegeneration, apoptosis, toxicity,
      neurocognitive impairment (developmental impairment and learning disorders) and
      anaesthesia (intravenous, inhalational and sedation). Results: From the initial
      search, 23 articles were identified as potentially relevant, with publication
      dates spanning from 1978 to 2012.  Twelve studies were deemed irrelevant to the
      research questions. The results of neurocognitive assessment from eight of the
      remaining eleven studies had showed some differences in the performances of
      children exposed to anaesthesia. The control population in these studies was
      highly variable. The age at which the subjects were exposed to anaesthesia ranged
      from prenatal to 4 years in the majority of studies with one including children
      aged up to 12 years when exposed. Discussion: Although there is clinical data
      suggesting a possible detrimental effect, the evidence is best considered
      preliminary and inconclusive at this stage. Many of the outcome measures were
      lacking in specificity and standardization in most cases. Parents should be
      counselled to not avoid necessary invasive procedures for fear of a currently ill
      defined risk.  However, deferral of elective procedures beyond the first few
      years of life should be contemplated.

PMID- 24327924
TI  - The RASSF1 Gene and the Opposing Effects of the RASSF1A and RASSF1C Isoforms on
      Cell Proliferation and Apoptosis.
AB  - RASSF1A has been demonstrated to be a tumor suppressor, while RASSF1C is now
      emerging as a growth promoting protein in breast and lung cancer cells. To
      further highlight the dual functionality of the RASSF1 gene, we have compared the
      effects of RASSF1A and RASSF1C on cell proliferation and apoptosis in the
      presence of TNF- alpha . Overexpression of RASSF1C in breast and lung cancer
      cells reduced the effects of TNF- alpha on cell proliferation, apoptosis, and
      MST1/2 phosphorylation, while overexpression of RASSF1A had the opposite effect.
      We also assessed the expression of RASSF1A and RASSF1C in breast and lung tumor
      and matched normal tissues. We found that RASSF1A mRNA levels are significantly
      higher than RASSF1C mRNA levels in all normal breast and lung tissues examined.
      In addition, RASSF1A expression is significantly downregulated in 92% of breast
      tumors and in 53% of lung tumors. Conversely, RASSF1C was upregulated in 62% of
      breast tumors and in 47% of lung tumors. Together, these findings suggest that
      RASSF1C, unlike RASSF1A, is not a tumor suppressor but instead may play a role in
      stimulating survival in breast and lung cancer cells. 

PMID- 24327925
TI  - Advances in Robotic-Assisted Radical Prostatectomy over Time.
AB  - Since the introduction of robot-assisted radical prostatectomy (RALP), robotics
      has become increasingly more commonplace in the armamentarium of the urologic
      surgeon. Robotic utilization has exploded across surgical disciplines well beyond
      the fields of urology and prostate surgery. The literature detailing technical
      steps, comparison of large surgical series, and even robotically focused
      randomized control trials are available for review. RALP, the first robot
      assisted surgical procedure to achieve widespread use, has recently become the
      primary approach for the surgical management of localized prostate cancer. As a
      result, surgeons are constantly trying to refine and improve upon current
      technical aspects of the operation. Recent areas of published modifications
      include bladder neck anastomosis and reconstruction, bladder drainage, nerve
      sparing approaches and techniques, and perioperative and postoperative management
      including penile rehabilitation. In this review, we summarize recent advances in
      perioperative management and surgical technique for RALP. 

PMID- 24327927
TI  - Fracture of the Atlas through a Synchondrosis of Anterior Arch.
AB  - Cervical fractures are rare in paediatric population. In younger children,
      cervical fractures usually occur above the level of C4; whereas in older
      population, fractures or dislocations more commonly involve the lower cervical
      spine. Greater elasticity of intervertebral ligaments and also the spinal
      vertebrae explains why cervical fractures in paediatric ages are rare. The injury
      usually results from a symmetric or asymmetric axial loading. In paediatric
      cases, most fractures occur through the synchondroses which are the weakest links
      of the atlas. The prognosis depends on the severity of the spinal cord injury. In
      this case, we presented an anterior fracture in synchondrosis of atlas after
      falling on head treated with cervical collar. There was no neurologic deficit for
      the following 2 years. 

PMID- 24327928
TI  - Risk factors for chronic mastitis in morocco and egypt.
AB  - Chronic mastitis is a prolonged inflammatory breast disease, and little is known
      about its etiology. We identified 85 cases and 112 controls from 5 hospitals in
      Morocco and Egypt. Cases were women with chronic mastitis (including periductal,
      lobular, granulomatous, lymphocytic, and duct ectasia with mastitis). Controls
      had benign breast disease, including fibroadenoma, benign phyllodes, and
      adenosis. Both groups were identified from histopathologically diagnosed patients
      from 2008 to 2011, frequency-matched on age. Patient interviews elicited
      demographic, reproductive, breastfeeding, and clinical histories. Cases had
      higher parity than controls (OR = 1.75, 1.62-1.90) and more reported history of
      contraception use (OR = 2.73, 2.07-3.61). Cases were less likely to report
      wearing a bra (OR = 0.56, 0.47-0.67) and less often used both breasts for
      breastfeeding (OR = 4.40, 3.39-5.72). Chronic mastitis cases were significantly
      less likely to be employed outside home (OR = 0.71, 0.60-0.84) and more likely to
      report mice in their households (OR = 1.63, 1.36-1.97). This is the largest case
      control study reported to date on risk factors for chronic mastitis. Our study
      highlights distinct reproductive risk factors for the disease. Future studies
      should further explore these factors and the possible immunological and
      susceptibility predisposing conditions. 

PMID- 24327926
TI  - Molecular mechanisms of treadmill therapy on neuromuscular atrophy induced via
      botulinum toxin A.
AB  - Botulinum toxin A (BoNT-A) is a bacterial zinc-dependent endopeptidase that acts
      specifically on neuromuscular junctions. BoNT-A blocks the release of
      acetylcholine, thereby decreasing the ability of a spastic muscle to generate
      forceful contraction, which results in a temporal local weakness and the atrophy
      of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to
      manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy,
      and cervical dystonia. However, the combined effect of treadmill exercise and
      BoNT-A treatment is not well understood. We previously demonstrated that for
      rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running
      improved the recovery of the sciatic functional index (SFI), muscle contraction
      strength, and compound muscle action potential (CMAP) amplitude and area.
      Treadmill training had no influence on gastrocnemius mass that received BoNT-A
      injection, but it improved the maximal contraction force of the gastrocnemius,
      and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine
      receptor (AChR) subunits alpha and beta was found following treadmill training.
      Taken together, these results suggest that the upregulation of genes associated
      with neurite and AChR regeneration following treadmill training may contribute to
      enhanced gastrocnemius strength recovery following BoNT-A injection. 

PMID- 24327930
TI  - Brain injury after transient global cerebral ischemia and subarachnoid
      hemorrhage.

PMID- 24327931
TI  - Spectral studies of a Cr(PNP)-MAO system for selective ethylene trimerization
      catalysis: searching for the active species.
AB  - Variable temperature spectroscopic, kinetic, and chemical studies were performed
      on a soluble CrIIICl3(PNP) (PNP = bis(diarylphosphino)alkylamine) ethylene
      trimerization precatalyst to map out its methylaluminoxane (MAO) activation
      sequence. These studies indicate that treatment of CrIIICl3(PNP) with MAO leads
      to first replacement of chlorides with alkyl groups, followed by alkyl
      abstraction, and then reduction to lower-valent species. Reactivity studies
      demonstrate that the majority of the chromium species detected is not
      catalytically active.

PMID- 24327932
TI  - Contribution of regulatory T cells to immunosuppression and disease progression
      in multiple myeloma patients.
AB  - Multiple myeloma (MM) patients exhibit consistent degrees of immune dysfunction.
      Regulatory T cells contribute to the establishment of an immunosuppressive status
      in MM patients, hence favoring disease progression.

PMID- 24327929
TI  - A compendium of urinary biomarkers indicative of glomerular podocytopathy.
AB  - It is well known that glomerular podocyte injury and loss are present in numerous
      nephropathies and that the pathophysiologic consecution of disease hinges upon
      the fate of the podocyte. While multiple factors play a hand in glomerulopathy
      progression, basic logic lends that if one monitors the podocyte's status, that
      may reflect the status of disease. Recent investigations have focused on what one
      can elucidate from the noninvasive collection of urine, and have proven that
      certain, specific biomarkers of podocytes can be readily identified via varying
      techniques. This paper has brought together all described urinary biomarkers of
      podocyte injury and is made to provide a concise summary of their utility and
      testing in laboratory and clinical theatres. While promising in the potential
      that they hold as tools for clinicians and investigators, the described
      biomarkers require further comprehensive vetting in the form of larger clinical
      trials and studies that would give their value true weight. These urinary
      biomarkers are put forth as novel indicators of glomerular disease presence,
      disease progression, and therapeutic efficacy that in some cases may be more
      advantageous than the established parameters/measures currently used in practice.

PMID- 24327933
TI  - RON promotes the metastatic spread of breast carcinomas by subverting antitumor
      immune responses.
AB  - The MSP/RON signaling pathway favors the conversion of micrometastatic lesions to
      overt metastases by suppressing antitumor immune responses. The loss of RON
      functions in the host potentiates tumor-specific CD8+ T-cell responses, hence
      inhibiting the outgrowth of metastatic cancer cells. Thus, RON inhibitors may
      potentially prevent the outgrowth of micrometastases in cancer patients.

PMID- 24327934
TI  - Overcoming immunosuppression as a new immunotherapeutic approach against
      pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of
      malignancy. Via a broad stimulation of the immune system, PDAC activates both
      antitumor immune responses and immunosuppressive mechanisms. We propose that new
      immunotherapeutic strategies for the management of PDAC should be designed to
      specifically neutralize the immunosuppressive tumor microenvironment.

PMID- 24327935
TI  - Immune ambivalence: The schizophrenic bleomycin.
AB  - In addition to cytotoxic effects, anticancer agents can exert multiple
      immunomodulatory functions. We have recently described the molecular mechanisms
      whereby bleomycin can 1) promote endoplasmic reticulum stress, causing the
      immunogenic death of cancer cells and hence strengthening antitumor CD8+ T cell
      responses; and 2) induce the secretion of transforming growth factor beta
      (TGFbeta), which stimulates regulatory T cells. This suggests that bleomycin may
      be favorably combined with TGFbeta-targeting strategies.

PMID- 24327936
TI  - Inhibition of the mevalonate pathway to override chemoresistance and promote the
      immunogenic demise of cancer cells: Killing two birds with one stone.
AB  - The mevalonate pathway is an attractive target for cancer therapy not only to
      override multidrug resistance but also to promote the immunogenic demise of
      malignant cells. Recent data indicate that aminobisphosphonates are superior to
      statins for the pharmacological manipulation of the mevalonate pathway, since
      they exert therapeutically relevant effects on both cancer cells and the immune
      system.

PMID- 24327937
TI  - Long peptide-based cancer immunotherapy targeting tumor antigen-specific CD4+ and
      CD8+ T cells.
AB  - CD4+ T cells promote cytotoxic T lymphocyte (CTL)-mediated anticancer immune
      responses. We have recently identified ideal tumor-associated antigen (TAA)
      derived long peptides (LPs) that elicit not only TAA-specific TH1 response, but
      also CTLs, through cross-presentation. The LP-specific TH1 cell responses were
      augmented in cancer patients vaccinated with CTL epitopes. Our findings support
      the clinical application of LP-based immunotherapy.

PMID- 24327938
TI  - Enhancing immunotherapy using chemotherapy and radiation to modify the tumor
      microenvironment.
AB  - The tumor microenvironment is a complex assortment of cells that includes a
      variety of leukocytes. The overall effect of the microenvironment is to support
      the growth of tumors and suppress immune responses. Immunotherapy is a highly
      promising form of cancer treatment, but its efficacy can be severely compromised
      by an immunosuppressive tumor microenvironment. Chemotherapy and radiation
      treatment can mediate tumor reduction through cytotoxic effects, but it is
      becoming increasingly clear that these forms of treatment can be used to modify
      the tumor microenvironment to liberate tumor antigens and decrease
      immunosuppression. Chemotherapy and radiotherapy can be used to modulate the
      tumor microenvironment to enhance immunotherapy.

PMID- 24327940
TI  - Level of respiratory protection against influenza virus.

PMID- 24327939
TI  - Monitoring NK cell activity in patients with hematological malignancies.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system that can
      recognize and kill various types of malignant cells. Monitoring the activity of
      peripheral NK cells in patients affected by hematological malignancies may
      provide prognostic information or unveil ongoing tumor-specific immune responses.
      Moreover, further insights into the biology of NK cells might also promote the
      development of novel strategies for stimulating their anticancer activity. Here,
      we review the main methods to monitor phenotypic and functional NK cell
      properties in cancer patients, focusing on individuals affected by multiple
      myeloma, a hematological malignancy currently treated with immunomodulatory
      drugs.

PMID- 24327941
TI  - Contribution of AcrAB efflux pump to ciprofloxacin resistance in Klebsiella
      pneumoniae isolated from burn patients.
AB  - Resistance to fluoroquinolones has been recently increased among bacterial
      strains isolated from outpatients. Multidrug-resistant K. pneumoniae is one of
      the major organisms isolated from burn patients and the AcrAB efflux pump is the
      principal pump contributing to the intrinsic resistance in K. pneumoniae against
      multiple antimicrobial agents including ciprofloxacin and other fluoroquinolones.
      Fifty-two K. pneumoniae isolated from burn patients in Shahid Motahari hospital
      and confirmed by conventional biochemical tests. Antimicrobial susceptibility
      testing was done according to CLSI 2011 guidelines, to determine the
      antimicrobial resistance pattern of isolates. AcrA gene was detected among
      ciprofloxacin-resistant isolates by PCR assay. MICs to ciprofloxacin were
      measured with and without carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Forty
      out of the 52 K. pneumoniae isolated from burn patients in Shahid Motahari
      hospital were resistant to ciprofloxacin according to breakpoint of CLSI
      guideline. PCR assay for acrA gene demonstrated that all ciprofloxacin-resistant
      isolates harbored acrA gene coding the membrane fusion protein AcrA and is a part
      of AcrAB efflux system. Among these isolates, 19 strains (47.5%) showed 2 to 32
      fold reduction in MICs after using CCCP as an efflux pump inhibitor. The other 21
      strains (52.5%) showed no disparity in MICs before and after using CCCP. In
      conclusion, the AcrAB efflux system is one of the principal mechanisms contribute
      in ciprofloxacin resistance among K. pneumoniae isolates but there are some other
      mechanisms interfere with ciprofloxacin resistance such as mutation in target
      proteins of DNA gyrase of topoisomerase IV enzymes. 

PMID- 24327942
TI  - Comparison between phenotypic and PCR for detection of OXA-23 type and metallo
      beta-lactamases producer Acinetobacter spp.
AB  - BACKGROUND: Resistance to carbapenems is developing around the world and can
      cause many problems for treatment of patients. Production of metallo-beta
      lactamase (MBL) is one of the main mechanism for this type of resistance. So,
      detection of MBL-producer microorganisms can prevent the spread of this type of
      resistance. MATERIALS AND METHODS: In this study 94 Acinetobacter spp. were
      investigated. Resistance to imipenem was conducted after purification and
      identification. Combination disc (CD) and Double Disc Synergy Test (DDST) were
      performed for phenotypic detection of MBL and the molecular PCR method was done
      for vim-1, vim-2, imp-1 and OXA-23 genes. RESULTS: According to TSI, SIM and
      oxidation-fermentation (OF) test and PCR assay 93 Acinetobacter baumannii and one
      strain Acinetobacter lwoffii were identified. 85% of them were resistant to
      imipenem. 34% of them have a positive combination disc test (CD) while Double
      Disc Synergy Test (DDST) was negative for all of them. The vim-1, vim-2 and imp-1
      genes were not detected in PCR molecular method, however in 74% of strains with
      positive results in combination disc, were positive for the OXA-23 gene after PCR
      test. This study shows that the blaOXA-23 resistance determinant may become an
      emerging therapeutic problem. DISCUSSION: According to the results, it seems that
      combination disc does not have enough specificity for detection of MBL-producer
      Acinetobacter and using Double Disc Synergy Test (DDST) can be more convenient.

PMID- 24327943
TI  - Serial IGRA testing of trainees in the healthcare sector in a country with low
      incidence for tuberculosis - a prospective cohort study.
AB  - BACKGROUND: Healthcare workers (HCW) are a risk group for tuberculosis (TB). That
      is why interferon-gamma release assay (IGRA) serial testing is performed on HCWs
      repeatedly exposed to infectious patients or materials. However, the variability
      of IGRA in serial testing is not yet well understood. We therefore analysed the
      prevalence of positive IGRA results as well as conversion and reversion rates in
      the serial testing of healthcare trainees in a low-incidence country. METHODS: In
      a prospective cohort study, all trainees (n=194) who began training as a nurse or
      healthcare worker at the Vivantes Healthcare Training Institute in Berlin on 1
      October 2008 or 1 April 2009 were IGRA-tested at three different times during the
      three years of training. Socio-demographic data and possible risk factors (e.g.,
      TB contacts, time spent abroad, area of work) were recorded by means of a
      standardised questionnaire. The QuantiFERON Gold In-Tube (QFT) was used as an
      IGRA. RESULTS: At the beginning of the training the cohort comprised 194
      trainees. 70% were female. Their average age was 23. The prevalence of positive
      QFT was 2.1% (4/194). In the first follow-up test, 2 out of 154 (1.3%) tested
      IGRA-positive, 151 (98%) had constantly negative results. One IGRA was constantly
      positive (0.6%) and there was one conversion and one reversion (0.6%
      respectively). In the second follow-up (n=142) there was again one conversion
      (0.7%), one reversion and the one constantly positive test result in all three
      QFT. This trainee had active TB in 2002. All other test results were constantly
      negative (n=139; 98%). No case of active tuberculosis was diagnosed over the
      three-year observation period. Contact with TB patients was reported by 42
      (29.6%) trainees during the follow-up. The two trainees with a conversion in QFT
      had no known contact with TB patients. Discordant results in the three
      consecutive QFT were observed in three trainees (2.1%). Using a borderline zone
      from 0.2-0.7 IU/mL reduced the number of trainees with discordant results from
      three to one - a reversion. CONCLUSION: The prevalence rate of latent TB
      infection is low in healthcare trainees without known risk factors for TB
      infection in their history. The infection risk seems to be low in this population
      even though contacts with TB patients during the training were reported.
      Introducing a borderline zone for the interpretation of reversions and
      conversions in this cohort appears to be safe and reduces the number of
      discordant results and helps to avoid unnecessary chest X-rays and preventive
      treatment.

PMID- 24327944
TI  - Improving patient safety during insertion of peripheral venous catheters: an
      observational intervention study.
AB  - BACKGROUND: Peripheral venous catheters are frequently used in hospitalized
      patients but increase the risk of nosocomial bloodstream infection. Evidence
      based guidelines describe specific steps that are known to reduce infection risk.
      However, the degree of guideline implementation in clinical practice is not
      known. The aim of this study was to determine the use of specific steps for
      insertion of peripheral venous catheters in clinical practice and to implement a
      multimodal intervention aimed at improving both compliance and the optimum order
      of the steps. METHODS: The study was conducted at University Hospital Hamburg. An
      optimum procedure for inserting a peripheral venous catheter was defined based on
      three evidence-based guidelines (WHO, CDC, RKI) including five steps with 1A or
      1B level of evidence: hand disinfection before patient contact, skin antisepsis
      of the puncture site, no palpation of treated puncture site, hand disinfection
      before aseptic procedure, and sterile dressing on the puncture site. A research
      nurse observed and recorded procedures for peripheral venous catheter insertion
      for healthcare workers in four different departments (endoscopy, central
      emergency admissions, pediatrics, and dermatology). A multimodal intervention
      with 5 elements was established (teaching session, dummy training, e-learning
      tool, tablet and poster, and direct feedback), followed by a second observation
      period. During the last observation week, participants evaluated the
      intervention. RESULTS: In the control period, 207 insertions were observed, and
      202 in the intervention period. Compliance improved significantly for four of
      five steps (e.g., from 11.6% to 57.9% for hand disinfection before patient
      contact; p<0.001, chi-square test). Compliance with skin antisepsis of the
      puncture site was high before and after intervention (99.5% before and 99.0%
      after). Performance of specific steps in the correct order also improved (e.g.,
      from 7.7% to 68.6% when three of five steps were done; p<0.001). The intervention
      was described as helpful by 46.8% of the participants, as neutral by 46.8%, and
      as disruptive by 6.4%. CONCLUSIONS: A multimodal strategy to improve both
      compliance with safety steps for peripheral venous catheter insertion and
      performance of an optimum procedure was effective and was regarded helpful by
      healthcare workers.

PMID- 24327945
TI  - Hygienic safety of alcohol-based hand disinfectants and skin antiseptics.
AB  - PURPOSE: The aim of this study was to evaluate the overall risk of hand
      disinfectants and skin antiseptics to become contaminated with bacterial spores
      throughout the production process and the subsequent in-use period, hence posing
      a public health risk. METHODS: Microbiological assessment of primary packaging
      material was carried out and long-term survival of bacterial spores in alcohol
      was assessed using sporulated B. subtilis ATCC 6633 as a standard. In-use
      contamination of alcohol-based formulations was tested by repeated use over 12
      months under practical conditions and microbiological and physico-chemical data
      were determined. RESULTS: Among 625 containers analyzed, 542 did not yield any
      microbial growth. Median colony count for aerobic spore-forming bacteria was 0.2
      cfu/10 ml container content. No anaerobic spore-forming bacteria were detected.
      Additionally, long-term survival of bacterial spores in aliphatic C2-C3 alcohols
      revealed 1-propanol to reduce the number of spores most effectively, with 2
      propanol and ethanol having a somewhat less pronounced impact. In-use tests did
      not detect any microbial contamination or change in the physicochemical
      properties of the tested products over 12 months. CONCLUSIONS: Our data reveals
      that state-of-the-art production processes of alcohol-based hand rubs and
      antiseptics can be regarded safe. Primary packaging material and use were not
      found to pose a significant contamination risk as far as bacterial spores are
      concerned. Based on the data from this study, a microbial limit of <1 cfu/10 ml
      can be suggested as a quality-control threshold for finished goods to ensure high
      quality and safe products.

PMID- 24327946
TI  - Evaluation of reprocessing medical devices in 14 German regional hospitals and at
      27 medical practitioners' offices within the European context - consequences for
      European harmonization.
AB  - Safe reprocessing of medical devices through cleaning, disinfection, and
      sterilization is essential for the prevention of health care associated
      infections (HAI) and to guarantee patient safety. Several studies detected
      residual contamination and even severe infections of patients, despite carrying
      out reprocessing. To develop appropriate solutions, the existing situation in
      Germany and selected European countries was analyzed. Additionally, in 27 medical
      practitioners' offices and 14 hospitals, the true practice of reprocessing was
      analyzed using a questionnaire, a checklist, and inspection on site. A structured
      analysis of potential alternatives to the internal reprocessing was conducted
      within the German and European context. The results indicate that the conditions
      for the execution of the reprocessing process in the analyzed health facilities
      in southern Hesse (Germany) do not satisfy legal requirements. The detected
      deficiencies were consistent with other reports from Germany and Europe. The
      analysis gave insight into several reasons for the detected deficiencies. The
      three main reasons were the high costs for proper implementation, the subjective
      value assigned to the reprocessing unit in health care facilities, and deficits
      in monitoring by the health authority. Throughout the European Union, a similar
      regulatory framework for the performance of the reprocessing process exists,
      while the environment, structures of the health systems and administrative
      supervision vary significantly. The German states as well as selected European
      countries are currently discussing the challenges of increased quality-assured
      execution of the reprocessing process. For instance, the same supervisory system
      for hospitals and medical practitioners should be established at an equal
      standard. Alternatives such as the use of single-use medical devices, outsourcing
      the decontamination processes, or the cooperation of health facilities may be
      considered. This paper also discusses economic and ecological aspects. Finally,
      different options are recommended to ensure the exclusive use of reliable medical
      devices for surgical procedures that guarantee an adequate standard of patient
      safety within economic constraints. 

PMID- 24327947
TI  - PP2Ce: Fat and stressed out?

PMID- 24327948
TI  - Hunting for the functions of short leptin receptor isoforms.

PMID- 24327949
TI  - The hormonal signature of energy deficit: Increasing the value of food reward.
AB  - Energy deficit is characterised by high ghrelin levels, and low leptin and
      insulin levels and we suggest that this provides a metabolic signature sensed by
      the brain to increase motivated behaviour to obtain food. We believe that the
      hormonal profile of negative energy balance serves to increase the incentive
      salience (or the value) of a food reinforcer, which in turn leads to increased
      motivation to obtain this reinforcer. These processes are mediated by a number of
      alterations in the mesolimbic dopamine system which serves to increase dopamine
      availability in the forebrain during energy deficit. The currently available
      evidence suggests that changes in motivational state, rather than hedonic
      enjoyment of taste, are primarily affected by reduced energy availability. This
      review aims to clarify the term 'reward' in the metabolic literature and promote
      more focused discussion in future studies. 

PMID- 24327950
TI  - Genetic and epigenetic control of metabolic health.
AB  - Obesity is characterized as an excess accumulation of body fat resulting from a
      positive energy balance. It is the major risk factor for type 2 diabetes (T2D).
      The evidence for familial aggregation of obesity and its associated metabolic
      diseases is substantial. To date, about 150 genetic loci identified in genome
      wide association studies (GWAS) are linked with obesity and T2D, each accounting
      for only a small proportion of the predicted heritability. However, the
      percentage of overall trait variance explained by these associated loci is modest
      (~5-10% for T2D, ~2% for BMI). The lack of powerful genetic associations suggests
      that heritability is not entirely attributable to gene variations. Some of the
      familial aggregation as well as many of the effects of environmental exposures,
      may reflect epigenetic processes. This review summarizes our current knowledge on
      the genetic basis to individual risk of obesity and T2D, and explores the
      potential role of epigenetic contribution. 

PMID- 24327951
TI  - Regulation of beta-cell function by RNA-binding proteins.
AB  - beta-cells of the pancreatic islets are highly specialized and high-throughput
      units for the production of insulin, the key hormone for maintenance of glucose
      homeostasis. Elevation of extracellular glucose and/or GLP-1 levels triggers a
      rapid upregulation of insulin biosynthesis through the activation of post
      transcriptional mechanisms. RNA-binding proteins are emerging as key factors in
      the regulation of these mechanisms as well as in other aspects of beta-cell
      function and glucose homeostasis at large, and thus may be implicated in the
      pathogenesis of diabetes. Here we review current research in the field, with a
      major emphasis on RNA-binding proteins that control biosynthesis of insulin and
      other components of the insulin secretory granules by modulating the stability
      and translation of their mRNAs. 

PMID- 24327952
TI  - Neuroinflammatory basis of metabolic syndrome.
AB  - Inflammatory reaction is a fundamental defense mechanism against threat towards
      normal integrity and physiology. On the other hand, chronic diseases such as
      obesity, type 2 diabetes, hypertension and atherosclerosis, have been causally
      linked to chronic, low-grade inflammation in various metabolic tissues. Recent
      cross-disciplinary research has led to identification of hypothalamic
      inflammatory changes that are triggered by overnutrition, orchestrated by
      hypothalamic immune system, and sustained through metabolic syndrome-associated
      pathophysiology. While continuing research is actively trying to underpin the
      identity and mechanisms of these inflammatory stimuli and actions involved in
      metabolic syndrome disorders and related diseases, proinflammatory IkappaB kinase
      beta (IKKbeta), the downstream nuclear transcription factor NF-kappaB and some
      related molecules in the hypothalamus were discovered to be pathogenically
      significant. This article is to summarize recent progresses in the field of
      neuroendocrine research addressing the central integrative role of
      neuroinflammation in metabolic syndrome components ranging from obesity, glucose
      intolerance to cardiovascular dysfunctions. 

PMID- 24327953
TI  - Phenotypic effects of an induced mutation of the ObRa isoform of the leptin
      receptor.
AB  - Leptin receptors play critical roles in mediating leptin's pleiotropic effects on
      mammalian physiology. To date, six splice variants of the leptin receptor gene
      have been identified [1-3]. These splice variants have identical extracellular
      leptin binding motifs but different intracellular C termini. The finding that
      mutations specifically ablating the function of ObRb cause obesity has
      established a critical role for this isoform in leptin signaling [1,7]. ObRa is
      the most abundant splicing isoform with a broad tissue distribution [5], and it
      has been proposed to play roles in regulating leptin bioavailability, CSF
      (cerebrospinal fluid) transport and function by forming heterodimers with ObRb
      and also activating signal transduction via JAK2 in-vitro [5-10]. To assess the
      in-vivo role of ObRa, we generated an ObRa KO mouse by deleting the ObRa-specific
      exon 19a. Homozygous mutant mice breed normally and are indistinguishable from
      wild-type mice on regular chow diet, but show a slightly increased basal plasma
      leptin, a slight improvement of their GTT and a slightly reduced response to
      systemic leptin administration. These mice also show a modest but statistically
      significant increase in weight when placed on a high fat diet with a slightly
      reduced CSF/plasma ratio of leptin. These data suggest that ObRa plays a role in
      mediating some of leptin's effects but that the phenotypic consequences are
      modest compared to a deletion of ObRb. 

PMID- 24327954
TI  - Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin
      cells.
AB  - The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory
      hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric
      ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively
      identified and functionally characterized using in vitro, ex vivo and in vivo
      methods. Five Galphas-coupled receptors efficiently stimulated ghrelin secretion:
      as expected the beta1-adrenergic, the GIP and the secretin receptors but
      surprisingly also the composite receptor for the sensory neuropeptide CGRP and
      the melanocortin 4 receptor. A number of Galphai/o-coupled receptors inhibited
      ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and
      unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite
      receptors known to be both Galphai/o- and Galphaq/11-coupled all inhibited
      ghrelin secretion through a pertussis toxin-sensitive Galphai/o pathway: FFAR2
      (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor;
      GPR120) and CasR (calcium sensing receptor). In addition to the common Galpha
      subunits three non-common Galphai/o subunits were highly enriched in ghrelin
      cells: GalphaoA, GalphaoB and Galphaz. Inhibition of Galphai/o signaling via
      ghrelin cell-selective pertussis toxin expression markedly enhanced circulating
      ghrelin. These 7TM receptors and associated Galpha subunits constitute a major
      part of the molecular machinery directly mediating neuronal and endocrine
      stimulation versus metabolite and somatostatin inhibition of ghrelin secretion
      including a series of novel receptor targets not previously identified on the
      ghrelin cell. 

PMID- 24327956
TI  - PPM1l encodes an inositol requiring-protein 1 (IRE1) specific phosphatase that
      regulates the functional outcome of the ER stress response.
AB  - The protein phosphatase 1-like gene (PPM1l) was identified as causal gene for
      obesity and metabolic abnormalities in mice. However, the underlying mechanisms
      were unknown. In this report, we find PPM1l encodes an endoplasmic reticulum (ER)
      membrane targeted protein phosphatase (PP2Ce) and has specific activity to basal
      and ER stress induced auto-phosphorylation of Inositol-REquiring protein-1
      (IRE1). PP2Ce inactivation resulted in elevated IRE1 phosphorylation and higher
      expression of XBP-1, CHOP, and BiP at basal. However, ER stress stimulated XBP-1
      and BiP induction was blunted while CHOP induction was further enhanced in PP2Ce
      null cells. PP2Ce protein levels are significantly induced during adipogenesis in
      vitro and are necessary for normal adipocyte maturation. Finally, we provide
      evidence that common genetic variation of PPM11 gene is significantly associated
      with human lipid profile. Therefore, PPM1l mediated IRE1 regulation and
      downstream ER stress signaling is a plausible molecular basis for its role in
      metabolic regulation and disorder. 

PMID- 24327955
TI  - Astroglial CB1 cannabinoid receptors regulate leptin signaling in mouse brain
      astrocytes.
AB  - Type-1 cannabinoid (CB1) and leptin (ObR) receptors regulate metabolic and
      astroglial functions, but the potential links between the two systems in
      astrocytes were not investigated so far. Genetic and pharmacological
      manipulations of CB1 receptor expression and activity in cultured cortical and
      hypothalamic astrocytes demonstrated that cannabinoid signaling controls the
      levels of ObR expression. Lack of CB1 receptors also markedly impaired leptin
      mediated activation of signal transducers and activators of transcription 3 and 5
      (STAT3 and STAT5) in astrocytes. In particular, CB1 deletion determined a basal
      overactivation of STAT5, thereby leading to the downregulation of ObR expression,
      and leptin failed to regulate STAT5-dependent glycogen storage in the absence of
      CB1 receptors. These results show that CB1 receptors directly interfere with
      leptin signaling and its ability to regulate glycogen storage, thereby
      representing a novel mechanism linking endocannabinoid and leptin signaling in
      the regulation of brain energy storage and neuronal functions. 

PMID- 24327957
TI  - Diet-induced changes in the Lean Brain: Hypercaloric high-fat-high-sugar snacking
      decreases serotonin transporters in the human hypothalamic region.
AB  - It is evident that there is a relationship between the brain's serotonin system
      and obesity. Although it is clear that drugs affecting the serotonin system
      regulate appetite and food intake, it is unclear whether changes in the serotonin
      system are cause or consequence of obesity. To determine whether obesogenic
      eating habits result in reduced serotonin transporter (SERT)-binding in the human
      hypothalamic region, we included 25 lean, male subjects who followed a 6-week
      hypercaloric diet, which were high-fat-high-sugar (HFHS) or high-sugar (HS) with
      increased meal size or -frequency (=snacking pattern). We measured SERT-binding
      in the hypothalamic region with SPECT. All hypercaloric diets significantly
      increased body weight by 3-3.5%. Although there were no differences in total
      calories consumed between the diets, only a hypercaloric HFHS-snacking diet
      decreased SERT-binding significantly by 30%. We here show for the first time in
      humans that snacking may change the serotonergic system increasing the risk to
      develop obesity. 

PMID- 24327958
TI  - Loss of neurotensin receptor-1 disrupts the control of the mesolimbic dopamine
      system by leptin and promotes hedonic feeding and obesity.
AB  - Neurons of the lateral hypothalamic area (LHA) control motivated behaviors such
      as feeding and ambulatory activity, in part by modulating mesolimbic dopamine
      (DA) circuits. The hormone, leptin, acts via the long form of the leptin receptor
      (LepRb) in the brain to signal the repletion of body energy stores, thereby
      decreasing feeding and promoting activity. LHA LepRb neurons, most of which
      contain neurotensin (Nts; LepRb(Nts) neurons) link leptin action to the control
      of mesolimbic DA function and energy balance. To understand potential roles for
      Nts in these processes, we examined mice null for Nts receptor 1 (NtsR1KO). While
      NtsR1KO mice consume less food than controls on a chow diet, they eat more and
      become obese when fed a high-fat, high-sucrose palatable diet; NtsR1KO mice also
      exhibit augmented sucrose preference, consistent with increased hedonic feeding
      in these animals. We thus sought to understand potential roles for NtsR1 in the
      control of the mesolimbic DA system and LHA leptin action. LHA Nts cells project
      to DA-containing midbrain areas, including the ventral tegmental area (VTA) and
      the substantia nigra (SN), where many DA neurons express NtsR1. Furthermore, in
      contrast to wild-type mice, intra-LHA leptin treatment increased feeding and
      decreased VTA Th expression in NtsR1KO mice, consistent with a role for NtsR1
      signaling from LHA LepRb neurons in the suppression of food intake and control of
      mesolimbic DA function. Additionally, these data suggest that other leptin
      regulated LHA neurotransmitters normally oppose aspects of Nts action to promote
      balanced responses to leptin. 

PMID- 24327959
TI  - Phenotypic comparison of common mouse strains developing high-fat diet-induced
      hepatosteatosis.
AB  - Genetic predisposition and environmental factors contribute to an individual's
      susceptibility to develop hepatosteatosis. In a systematic, comparative survey we
      focused on genotype-dependent and -independent adaptations early in the
      pathogenesis of hepatosteatosis by characterizing C3HeB/FeJ, C57BL/6NTac,
      C57BL/6J, and 129P2/OlaHsd mice after 7, 14, or 21 days high-fat-diet exposure.
      Strain-specific metabolic responses during diet challenge and liver transcript
      signatures in mild hepatosteatosis outline the suitability of particular strains
      for investigating the relationship between hepatocellular lipid content and
      inflammation, glucose homeostasis, insulin action, or organelle physiology.
      Genetic background-independent transcriptional adaptations in liver paralleling
      hepatosteatosis suggest an early increase in the organ's vulnerability to
      oxidative stress damage what could advance hepatosteatosis to steatohepatitis.
      "Universal" adaptations in transcript signatures and transcription factor
      regulation in liver link insulin resistance, type 2 diabetes mellitus, cancer,
      and thyroid hormone metabolism with hepatosteatosis, hence, facilitating the
      search for novel molecular mechanisms potentially implicated in the pathogenesis
      of human non-alcoholic-fatty-liver-disease. 

PMID- 24327960
TI  - Bile acid-induced inflammatory signaling in mice lacking Foxa2 in the liver leads
      to activation of mTOR and age-onset obesity.
AB  - Cytokine signaling has been connected to regulation of metabolism and energy
      balance. Numerous cytokine gene expression changes are stimulated by accumulation
      of bile acids in livers of young Foxa2 liver-conditional null mice. We
      hypothesized that bile acid-induced inflammation in young Foxa2 mutants, once
      chronic, affects metabolic homeostasis. We found that loss of Foxa2 in the liver
      results in a premature aging phenotype, including significant weight gain,
      reduced food intake, and decreased energy expenditure. We show that Foxa2
      antagonizes the mammalian target of rapamycin (mTOR) pathway, resulting in
      increased hepatic lipogenesis and adiposity. While much prior work has focused on
      adipose tissue in obesity, we discovered a novel age-onset obesity phenotype in a
      model where gene deletion occurs only in the liver, underscoring the importance
      of the role hepatic lipogenesis plays in the development of obesity. 

PMID- 24327962
TI  - Peptide lipidation stabilizes structure to enhance biological function.
AB  - Medicines that decrease body weight and restore nutrient tolerance could improve
      human diabetes and obesity treatment outcomes. We developed lipid-acylated
      glucagon analogs that are co-agonists for the glucagon and glucagon-like peptide
      1 receptors, and stimulate weight loss and plasma glucose lowering in pre
      diabetic obese mice. Our studies identified lipid acylation (lipidation) can
      increase and balance in vitro potencies of select glucagon analogs for the two
      aforementioned receptors in a lipidation site-dependent manner. A general
      capacity for lipidation to enhance the secondary structure of glucagon analogs
      was recognized, and the energetics of this effect quantified. The molecular
      structure of a lipid-acylated glucagon analog in water was also characterized.
      These results support that lipidation can modify biological activity through
      thermodynamically-favorable intramolecular interactions which stabilize
      structure. This establishes use of lipidation to achieve specific pharmacology
      and implicates similar endogenous post-translational modifications as
      physiological tools capable of refining biological action in means previously
      underappreciated. 

PMID- 24327961
TI  - Cholesteryl ester transfer protein protects against insulin resistance in obese
      female mice.
AB  - Cholesteryl ester transfer protein (CETP) shuttles lipids between lipoproteins,
      culminating in cholesteryl ester delivery to liver and increased secretion of
      cholesterol as bile. Since gut bile acids promote insulin sensitivity, we aimed
      to define if CETP improves insulin sensitivity with high-fat feeding. CETP and
      nontransgenic mice of both sexes became obese. Female but not male CETP mice had
      increased ileal bile acid levels versus nontransgenic littermates. CETP
      expression protected female mice from insulin resistance but had a minimal effect
      in males. In liver, female CETP mice showed activation of bile acid-sensitive
      pathways including Erk1/2 phosphorylation and Fxr and Shp gene expression. In
      muscle, CETP females showed increased glycolysis, increased mRNA for Dio2, and
      increased Akt phosphorylation, known effects of bile acid signaling. These
      results suggest that CETP can ameliorate insulin resistance associated with
      obesity in female mice, an effect that correlates with increased gut bile acids
      and known bile-signaling pathways. 

PMID- 24327963
TI  - Coenzyme Q10 prevents accelerated cardiac aging in a rat model of poor maternal
      nutrition and accelerated postnatal growth.
AB  - Studies in human and animals have demonstrated that nutritionally induced low
      birth-weight followed by rapid postnatal growth increases the risk of metabolic
      syndrome and cardiovascular disease. Although the mechanisms underlying such
      nutritional programming are not clearly defined, increased oxidative-stress
      leading to accelerated cellular aging has been proposed to play an important
      role. Using an established rodent model of low birth-weight and catch-up growth,
      we show here that post-weaning dietary supplementation with coenzyme Q10, a key
      component of the electron transport chain and a potent antioxidant rescued many
      of the detrimental effects of nutritional programming on cardiac aging. This
      included a reduction in nitrosative and oxidative-stress, telomere shortening,
      DNA damage, cellular senescence and apoptosis. These findings demonstrate the
      potential for postnatal antioxidant intervention to reverse deleterious
      phenotypes of developmental programming and therefore provide insight into a
      potential translatable therapy to prevent cardiovascular disease in at risk
      humans. 

PMID- 24327964
TI  - Ablation of TrkB expression in RGS9-2 cells leads to hyperphagic obesity.
AB  - Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB
      (tropomyosin receptor kinase B), are widely expressed in the brain where they
      regulate a wide variety of biological processes, including energy homeostasis.
      However, the specific population(s) of TrkB-expressing neurons through which BDNF
      governs energy homeostasis remain(s) to be determined. Using the Cre-loxP
      recombination system, we deleted the mouse TrkB gene in RGS9-2-expressing cells.
      In this mouse mutant, TrkB expression was abolished in several hypothalamic
      nuclei, including arcuate nucleus, dorsomedial hypothalamus, and lateral
      hypothalamus. TrkB expression was also abolished in a small number of cells in
      other brain regions, including the cerebral cortex and striatum. The mutant
      animals developed hyperphagic obesity with normal energy expenditure. Despite
      hyperglycemia under fed conditions, these animals exhibited normal fasting blood
      glucose levels and normal glucose tolerance. These results suggest that BDNF
      regulates energy homeostasis in part through TrkB-expressing neurons in the
      hypothalamus. 

PMID- 24327966
TI  - Application of case discussions to improve anatomy learning in Syria.
AB  - AIMS: Designing a new approach for learning gross anatomy to improve students'
      motivation to study anatomy and to enable them to learn independently through
      case discussion. MATERIALS AND METHODS: The study included newly registered
      students in the first academic year. The total number of students was 165, who
      were divided by alphabetical order into 15 groups of 11 students. Each group was
      led by one faculty member and each faculty member lead 3 groups. Each group met
      twice a week for 2 weeks to discuss one case related to the upper limb anatomy.
      Students took pre- and posttests and completed an opinion questionnaire about the
      case discussions. RESULTS: The pretest score shows that 20% of the students
      received grades of 60% or above and that 80% received grades less than 60%. The
      posttest showed that 45% of the students received grades of 60% or above and that
      55% received grades less than 60%. There was a significant difference between the
      pre- and posttest for grades <60% (P = 0.0000) and less significant for grades
      >60% (P = 0.0023). In addition, 17% of students achieved the same results (less
      than 60%) in both the pre- and posttests. The questionnaire revealed that all
      students stated that the discussion method was useful in their learning process,
      helped them to increase their motivation to study anatomy (85%), know the
      usefulness of studying anatomy (84%), and understand the problems (91%).
      CONCLUSIONS: The implementation of the case discussion in teaching anatomy can
      increase the students' understanding and motivate them to learn.

PMID- 24327965
TI  - In vivo analysis of the contribution of bone resorption to the control of glucose
      metabolism in mice.
AB  - Osteocalcin is a hormone produced in bones by osteoblasts and regulating energy
      metabolism. While osteocalcin exists in two forms, gamma-carboxylated and
      undercarboxylated only the latter appears to function as a hormone in vivo. It
      has been proposed recently that osteoclasts, the bone-resorbing cells, are
      responsible of decarboxylating, i.e. activating osteocalcin. To address the role
      of osteoclasts in the maintenance of energy metabolism we analyzed mutant mouse
      strains harboring either an increase or a decrease in osteoclasts number.
      Osteoprotegerin-deficient mice that are characterized by an increase in the
      number of osteoclasts demonstrate an increase in serum levels of
      undercarboxylated osteocalcin and are significantly more glucose tolerant than WT
      animals. Conversely, osteoclasts ablation in mice results in a decrease in serum
      undercarboxylated osteocalcin levels and in reduced glucose tolerance. These
      results support the notion that osteoclasts are controlling glucose metabolism at
      least in part through the regulation of osteocalcin decarboxylation. 

PMID- 24327967
TI  - Tigecycline activity against metallo-beta-lactamase-producing bacteria.
AB  - BACKGROUND: [corrected] Treatment of serious life-threatening multi-drug
      resistant organisms poses a serious problem due to the limited therapeutic
      options. Tigecycline has been recently marketed as a broad-spectrum antibiotic
      with activity against both gram-positive and gram-negative bacteria. Even though
      many studies have demonstrated the activity of tigecycline against ESBL-producing
      Enterobacteriaceae, its activity is not well-defined against micro-organisms
      producing metallo-beta-lactamases (MBLs), as there are only a few reports and the
      number of isolates tested is limited. AIMS: The aim of the present study was to
      evaluate the activity of tigecycline against MBL-producing bacterial isolates.
      MATERIALS AND METHODS: The isolates were tested for MBL production by (i)
      combined-disk test, (ii) double disc synergy test (DDST), (iii) susceptibility to
      aztreonam (30 MUg) disk. Minimum inhibitory concentration to tigecycline was
      determined according to agar dilution method as per Clinical Laboratory Standards
      Institute (CLSI) guidelines. Disc diffusion susceptibility testing was also
      performed for all these isolates using tigecycline (15 MUg) discs. RESULTS: Among
      the total 308 isolates included in the study, 99 were found to be MBL producers.
      MBL production was observed mostly in isolates from pus samples (40.47%) followed
      by urine (27.4%) and blood (13.09%). MBL production was observed in E. coli
      (41.48%), K. pneumoniae (26.67%), Proteus mirabilis (27.78%), Citrobacter spp.
      (41.67%), Enterobacter spp. (25.08%), and Acinetobacter spp. (27.27%). The result
      showed that tigecycline activity was unaffected by MBL production and it was
      showed almost 100% activity against all MBL-producing isolates, with most of the
      isolates exhibiting an MIC ranging from 0.25-8 MUg/ml, except 2 MBL-producing E.
      coli isolates who had an MIC of 8 MUg/ml. CONCLUSION: To conclude, tigecycline
      was found to be highly effective against MBL-producing Enterobacteriaceae and
      acinetobacter isolates, but the presence of resistance among organisms, even
      before the mass usage of the drug, warrants the need of its usage as a reserve
      drug. The study also found that the interpretative criteria for the disc
      diffusion method, recommended by the FDA, correlates well with the MIC detection
      methods. So, the microbiology laboratories might use the relatively easier method
      of disc diffusion, as compared to the comparatively tedious method of MIC
      determination.

PMID- 24327968
TI  - Frequency, risk factors, and antibiogram of Acinetobacter species isolated from
      various clinical samples in a tertiary care hospital in Odisha, India.
AB  - BACKGROUND: For the past two decades, Acinetobacter spp. have emerged as an
      important pathogen globally in various infections. OBJECTIVES: This study was
      conducted to determine the frequency, risk factors, and antibiotic resistance
      pattern of Acinetobacter spp. from various clinical samples. MATERIALS AND
      METHODS: This retrospective, hospital record-based, cross-sectional study
      included a total of 8749 clinical samples collected from patients at a tertiary
      care hospital in Odisha, India from July 2010 to December 2012. The samples were
      processed and identified by standard protocol. The Acinetobacter isolates were
      tested for antibiotic resistance by Kirby-Bauer disk diffusion method [according
      to the Clinical and Laboratory Standards Institute (CLSI) guidelines]. RESULTS:
      From 8749 clinical samples, 4589 (52.5%) yielded significant growth and only 137
      (3%, 137/4589) Acinetobacter spp. were isolated. Maximum (56.9%) isolates were
      obtained from pus/swab, followed by blood (13.1%) and urine (12.4%). Elderly age,
      being inpatients, longer duration of stay in the hospital, associated co
      morbidity, and invasive procedure were found to be significant risk factors in
      the setup investigated (P is less than 0.05). Out of 137 isolates, 75 (54.7%)
      were resistant to more than three classes of antibiotics (multidrug resistant)
      and 8 (5.8%) were resistant to all commonly used antibiotics (pan-drug
      resistant). Majority of the isolates were sensitive to imipenem, meropenem, and
      piperacillin/tazobactam, and showed resistance rates of 19%, 22%, and 23%,
      respectively. All eight pan-drug resistant isolates were 100% sensitive to
      colistin. CONCLUSION: This hospital-based epidemiological data will help to
      implement better infection control strategies and improve the knowledge of
      antibiotic resistance patterns in our region.

PMID- 24327969
TI  - Abdominal cocoon.
AB  - Abdominal cocoon is an acquired benign condition in which there is encapsulation
      of bowel loops by a fibrous membrane. Pre-operative clinical diagnosis is usually
      difficult. Imaging plays a critical role in timely and accurate diagnosis. We
      present a brief discussion on this topic with relevant imaging findings. 

PMID- 24327970
TI  - Management of sizeable carotid body tumor: Case report and review of literature.
AB  - Carotid body tumor is a paraganglioma derived from the neural crest. It arises
      from the carotid body which acts as a vascular chemoreceptors and is usually
      located at the carotid bifurcation. Sizeable (Shamblin III, >5 cm size) tumors
      are large and typically encase the carotid artery requiring vessel resection and
      replacement. Management of such tumors carries a high risk of postoperative
      mortality and morbidity rates specially with regards to neurovascular
      complications. We report a case of sizeable tumor which was surgically removed
      with minimal complications. 

PMID- 24327971
TI  - Acral gangrene as a presentation of non-uremic calciphylaxis.
AB  - We are describing a case of 55-year-old obese female with significant history of
      uncontrolled rheumatoid arthritis, who recently had decreased her immune
      suppression medications. She presented with extensive acral gangrene involving
      multiple fingers and toes. Clinical picture and laboratory findings were
      suggestive of vasculitis; however, skin biopsy established diagnosis of
      calciphylaxis, in settings of normal kidney function. Patient was treated with
      sodium thiosulfate with gradual improvement in her skin lesions. 

PMID- 24327972
TI  - We now take an initial step to the world!

PMID- 24327973
TI  - Pathogenesis and promising non-invasive markers for preeclampsia.
AB  - Preeclampsia is one of the leading causes of maternal mortality/morbidity and
      preterm delivery in the world, affecting 3% to 5% of pregnant women. The
      pathophysiology of preeclampsia likely involves both maternal and fetal/placental
      factors. Abnormalities in the development of placental vessels early in pregnancy
      may result in placental hypoperfusion, hypoxia, or ischemia. Hypoperfusion,
      hypoxia, and ischemia are critical components in the pathogenesis of preeclampsia
      because the hypoperfused placenta transfers many factors into maternal vessels
      that alter maternal endothelial cell function and lead to the systemic symptoms
      of preeclampsia. There are several hypotheses to explain the pathogenesis of
      preeclampsia, including altered angiogenic balance, circulating angiogenic
      factors (such as marinobufagenin, a bufadienolide trigger), and activation of the
      renin-angiotensin system. Epigenetically-modified cell-free nucleic acids that
      circulate in plasma and serum might be novel markers with promising non-invasive
      clinical applications in the diagnosis of preeclampsia. 

PMID- 24327974
TI  - Random urine protein/creatinine ratio readily predicts proteinuria in
      preeclampsia.
AB  - OBJECTIVE: To assess the diagnostic accuracy of random urine protein-creatinine
      (P/C) ratio for prediction of significant proteinuria in preeclampsia as an
      alternative to the time-consuming 24-hour urine protein collection. METHODS:
      Retrospective record analysis was performed on 140 pregnant women who were
      admitted with suspicion for preeclampsia from January 2006 to June 2011. Random
      urine protein and/or 24-hour urine protein levels were assessed and their
      correlation to random urine P/C ratio and 24-hour urine protein excretion was
      evaluated. RESULTS: Out of 140 patients, random urine P/C ratio or/and 24-hour
      urine protein was performed in 79 patients to evaluate significant proteinuria.
      Of 79 patients, 46 (58%) underwent both tests whereas in 33 women (42%) 24-hour
      urine collection was not available due to urgent delivery. In 39 cases (85%),
      significant proteinuria (>=300 mg/24 hr) was detected with 6 cases (13%) having
      values over 5,000 mg/24 hr, corresponding to the diagnosis of severe
      preeclampsia. Random urine P/C ratio highly correlated with 24-hour urine protein
      excretion (r=0.823, P<0.01). The optimal random urine P/C ratio cutoff points
      were 0.63 and 4.68 for 300 mg/24 hr and 5,000 mg/24 hr of protein excretion,
      respectively. with each sensitivity, specificity, and positive and negative
      predictive values of 87.1%, 100%, 100%, and 58.3%; and 100%, 85%, 50%, and 100%,
      for significant and severe preeclampsia, respectively. CONCLUSION: Random urine
      P/C ratio is a reliable indicator of significant proteinuria in preeclampsia and
      may be better at providing earlier diagnostic information than the 24-hour urine
      protein excretion with more accuracy than the urinary dipstick test.

PMID- 24327975
TI  - Promising treatment results of adjuvant chemotherapy following radical
      hysterectomy for intermediate risk stage 1B cervical cancer.
AB  - OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy of
      adjuvant chemotherapy following radical hysterectomy for intermediate risk stage
      IB cervical cancer. METHODS: From January 1993 to December 2007, a total of 100
      patients of stage IB were enrolled in this study who had at least two of the
      following three intermediate risk factors (deep stromal invasion, lymphovascular
      space involvement, and large tumor size) after radical hysterectomy and all
      patients had no high risk factors and no radiotherapy. Of these patients, 22
      patients had surgery only and 78 patients had cisplatin-based combination
      chemotherapy as adjuvant therapy postoperatively to improve survival. Kaplan
      Meier survival curves and Cox's proportional-hazards regression model and log
      rank test were used for survival analysis and to estimate the impact of
      prognostic factors on survival. RESULTS: The mean age was 52 years (range, 28 to
      76 years). The overall survival rate of all intermediate tumors are 92% (92/100).
      Surgery only group is 81.8% (18/22) and adjuvant chemotherapy group is 94.9%
      (74/78). Comparison of survival between two groups revealed significant
      statistical difference in both univariant and multivariant survival analysis
      (P<0.05). The main toxicities of adjuvant chemotherapy were bone marrow
      suppression (18%), nausea and vomiting (5.2%) and alopecia in etoposide-cisplatin
      chemotherapy group (100%) but most side effects of postoperative adjuvant
      chemotherapy were transient, reversible and within acceptable limits to all
      patients. CONCLUSION: Cisplatin based combined adjuvant chemotherapy for
      intermediate risk tumors after radical hysterectomy is promising with significant
      improvement of overall survival and with acceptable toxicity profile.

PMID- 24327976
TI  - Urinary nephrin: A new predictive marker for pregnancies with preeclampsia and
      small-for-gestational age infants.
AB  - OBJECTIVE: The objective of this study was to determine the differences in
      urinary nephrin among controls, gravidas with preeclampsia (PE), and small-for
      gestational age (SGA) infants. We also determined whether or not maternal urinary
      concentrations of nephrin are associated with the subsequent development of PE
      and SGA infants. METHODS: We analyzed maternal urinary levels of nephrin in women
      who were normal controls (n=50), women who were delivered SGA infants (n=40), and
      gravidas with PE (n=33) in the first, second and third trimesters. Urinary
      nephrin concentrations were measured with nephrin enzyme-linked immunosorbent
      assay kits. RESULTS: The levels of urinary nephrin were higher in gravida
      developing preeclampsia or SGA than in controls after adjusting serum creatinine
      (P<0.05 for both). Maternal urine concentrations of nephrin were higher in
      pregnancies complicated by SGA and PE in the third trimester (P<0.05), and also
      higher in pregnancies complicated by SGA in the first trimester (P<0.05). The
      sensitivity and specificity of nephrin in predicting SGA from normal pregnancies
      were 67% and 89% in the first trimester, 60% and 79% in the second trimester, and
      80% and 84% in the third trimester, respectively. The sensitivity and specificity
      of nephrin in predicting PE from normal pregnancies were 67% and 83% in the first
      trimester and 73% and 79% in the third trimester, respectively. CONCLUSION: We
      suggest that urinary nephrin can be used as an early marker in pregnancies at
      risk for developing PE and SGA infants.

PMID- 24327977
TI  - Prognostic value of serum CA-125 in patients with advanced epithelial ovarian
      cancer followed by complete remission after adjuvant chemotherapy.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic value of serum CA
      125 in advanced epithelial ovarian cancer with complete remission after primary
      adjuvant chemotherapy. METHODS: We reviewed the records of 120 patients with
      advanced epithelial ovarian cancer who underwent primary surgery followed by
      adjuvant therapy at our institution between January 1998 and December 2005.
      RESULTS: The median progression free survival was 21.6 months and 12.5 months in
      patients with nadir CA-125 levels <=10 U/mL and 10 to 35 U/mL, respectively.
      Median overall survival in the same respective order was 130.2 months and 35.3
      months. The level of serum CA-125 after the first cycle of adjuvant chemotherapy
      was most significantly higher in the recurrent group compared with the non
      recurrent group. The optimal cut point of CA-125 on the receiver operating
      characteristic curve was 35 U/mL. Median progression free survival was 64.6
      months and 12.8 months in patients with nadir CA-125 levels <=35 U/mL and >35
      U/mL, respectively, after first cycle of adjuvant chemotherapy. CONCLUSION: Serum
      CA-125 level after the first cycle of adjuvant chemotherapy is a strong
      independent prognostic factor for advanced epithelial ovarian cancer with
      complete response.

PMID- 24327978
TI  - Effect of myoma size on failure of thermal balloon ablation or levonorgestrel
      releasing intrauterine system treatment in women with menorrhagia.
AB  - OBJECTIVE: The aim of the present study was to identify variables associated with
      treatment failure in women with menorrhagia who were treated with thermal balloon
      ablation (TBA) or levonorgestrel releasing intrauterine system (LNG-IUS), and to
      determine if there are subgroups where one treatment type is more effective than
      the other. METHODS: The study included 106 women with menorrhagia who were
      treated with TBA or LNG-IUS at the study institute between January 2003 and
      December 2007, with a follow-up period greater than 12 months. Data were
      collected by retrospective review of medical records. Treatment failure was
      defined as persistent or recurrent menorrhagia within one year after treatment or
      hysterectomy at any time during follow-up. The relationships between variables
      and treatment outcome were analyzed using the chi-square or Fisher's exact test.
      The treatment outcome of TBA was compared with LNG-IUS. RESULTS: Sixty-seven
      women were treated with TBA and 39 women were managed with LNG-IUS. Fifty-two
      women had a myoma >=2.5 cm. Treatment failure was observed in 24 women (2
      recurrent or persistent menorrhagia and 22 hysterectomies) and myoma size (>=2.5
      cm vs. <2.5 cm) was associated with treatment outcome. TBA and LNG-IUS showed
      similar treatment outcomes. CONCLUSION: A large myoma is a risk factor for
      treatment failure in women with menorrhagia treated with TBA or LNG-IUS.

PMID- 24327979
TI  - Hepatoid carcinoma of the ovary without staining for alpha-fetoprotein.
AB  - Primary hepatoid carcinoma of the ovary (HCO) is a rare type of ovarian tumor
      that resembles hepatocellular carcinoma both histologically and
      immunohistochemically in its staining for alpha-fetoprotein (AFP). We describe a
      51-year-old woman who presented to our hospital complaining of abdominal pain.
      Computed tomography scan revealed a large tumor in the pelvis. She underwent
      total hysterectomy and bilateral salpingo-oophorectomy with tumorectomy. A right
      ovarian mass measuring 9*8*6 cm was found. Histological diagnosis was hepatoid
      carcinoma of the right ovary. But, immunohistochemically, tumor cells were not
      immunoreactive for AFP and there was no elevation of serum AFP level. This is the
      first report of an ovarian carcinoma with typical histologic features of HCO with
      negative staining for AFP and normal level of serum AFP in the world. 

PMID- 24327980
TI  - Intraoperative uterine artery embolization without fetal radiation exposure in
      patients with placenta previa totalis: Two case reports.
AB  - Embolization of the uterine arteries is a valuable method for controlling
      postpartum hemorrhage. There have been recent attempts to apply this tool as a
      means of controlling bleeding during Cesarean section, especially in patients
      with placenta previa. However, the benefits are controversial due to lack of
      randomized controlled studies, no evidence of significant improved outcomes, and
      potential harm including radiation exposure. This paper includes two case reports
      of intraoperative uterine artery embolization without fetal radiation exposure in
      patients with placenta previa totalis. 

PMID- 24327981
TI  - An asymptomatic ovarian steroid cell tumor with complete cystic morphology: A
      case report.
AB  - Steroid cell tumors of the ovary are extremely rare, accounting for only 0.1% of
      all ovarian tumors. Of these, steroid cell tumors, not otherwise specified (NOS)
      constitute about 56% of all steroid cell tumors. Most steroid cell tumors secrete
      steroid hormones, and only about 10% to 15% of patients are asymptomatic. The
      morphology of steroid cell tumors, NOS is predominantly reported to be solid, and
      a review of case reports from 1979 until now revealed only 5 cases that were
      mainly cystic tumors. The present case, in a patient who had undergone a previous
      hysterectomy and surgery for a peritoneal inclusion cyst, is reported due to its
      rarity and its unusual presentation, together with a brief review of the
      literature. The tumor showed no clinical signs and symptoms typical of a steroid
      hormone secreting tumor and had an atypical morphology, being primarily multi
      septate cystic with a minor solid portion. 

PMID- 24327982
TI  - Obstetrics & Gynecology Science, on the runway.

PMID- 24327983
TI  - Non-invasive prenatal diagnosis of fetal trisomy 21 using cell-free fetal DNA in
      maternal blood.
AB  - Since the existence of cell-free fetal DNA (cff-DNA) in maternal circulation was
      discovered, it has been identified as a promising source of fetal genetic
      material in the development of reliable methods for non-invasive prenatal
      diagnosis (NIPD) of fetal trisomy 21 (T21). Currently, a prenatal diagnosis of
      fetal T21 is achieved through invasive techniques, such as chorionic villus
      sampling or amniocentesis. However, such invasive diagnostic tests are expensive,
      require expert technicians, and have a miscarriage risk approximately 1%.
      Therefore, NIPD using cff-DNA in the detection of fetal T21 is significant in
      prenatal care. Recently, the application of new techniques using single-molecular
      counting methods and the development of fetal-specific epigenetic markers has
      opened up new possibilities in the NIPD of fetal T21 using cff-DNA. These new
      technologies will facilitate safer, more sensitive and accurate prenatal tests in
      the near future. In this review, we investigate the recent methods for the NIPD
      of fetal T21 and discuss their implications in future clinical practice. 

PMID- 24327985
TI  - Clinicopathological significance of atypical glandular cells on Pap smear.
AB  - OBJECTIVE: To investigate the clinical significance of atypical glandular cells
      (AGC) by analyzing the prevalence and histologic outcomes of patients with AGC
      according to Pap smear. METHODS: The medical records of 83 patients who were
      diagnosed AGC on Pap tests at the Pusan National University Hospital outpatient
      department and health care center from January 1998 to March 2006 were reviewed.
      RESULTS: The prevalence of AGC was 55 of 54,160 (0.10%) and 28 of 54,160 (0.05%)
      for AGC-not otherwise specified (NOS) and neoplastic associated AGC,
      respectively. The histopathologic results of the AGC-NOS group (n=55) were as
      follows: low-grade squamous intraepithelial lesion, 7 (12.7%); high-grade
      squamous intraepithelial lesion, 4 (7.2%); adenocarcinoma of cervix, 3 (5.4%);
      endometrial carcinoma, 2 (3.6%); and other malignancies including 2 ovarian
      cancer cases and 1 breast cancer case, 3 (5.4%). The histopathologic results for
      the AGC-associated neoplastic group (n=28) were as follows: low-grade squamous
      intraepithelial lesion, 1 (3.5%); high-grade squamous intraepithelial lesion, 3
      (10.7%); adenocarcinoma of cervix, 5 (17.8%); endometrial carcinoma, 4 (4.8%);
      and additional malignancies including 3 stomach cancer cases, 2 ovarian cancer
      cases, and 2 breast cancer cases; 7 (25%). CONCLUSION: AGCs may represent a
      variety of benign and malignant lesions. AGC-associated neoplastic findings may
      be related to gynecological or extrauterine malignancies. Thus, when AGCs,
      especially neoplastic AGCs, are encountered, it is best to evaluate the cervix
      not only for typical maladies, but also for gynecological and non-gynecological
      malignancies.

PMID- 24327984
TI  - Clinical applications of levonorgestrel-releasing intrauterine system to
      gynecologic diseases.
AB  - The levonorgestrel-releasing intrauterine system (LNG-IUS), originally designed
      for contraception, has since been applied to various gynecologic diseases. This
      article summarizes the current status of clinical applications of LNG-IUS to the
      treatment of gynecologic diseases such as heavy menstrual bleeding,
      endometriosis, leiomyoma, adenomyosis, endometrial hyperplasia, and early-stage
      endometrial cancer. 

PMID- 24327986
TI  - Regulation of paclitaxel-induced programmed cell death by autophagic induction: A
      model for cervical cancer.
AB  - OBJECTIVE: Autophagy plays a vital role in homeostasis by combining organelles
      and cellular proteins with lysosome under starvation conditions. In addition,
      autophagy provides tumor cells with a source of energy. Continued autophagy will
      induce cells death. Here we aim to see if autophagic induction has an effect on
      conventional chemotherapeutic agents. METHODS: Rapamycin, or mammalian target of
      rapamycin and paclitaxel, apoptosis-inducing agents were used autophagy in HeLa
      cervical cancer cells. RESULTS: Growth inhibition of cells was not observed after
      the application of 0, 10, 20 nM of paclitaxel with or without rapamycin. Using a
      5 nM concentration of paclitaxel, rapamycin administration inhibited cell growth
      significantly compared to no treatment. This implies the synergic antitumor
      effect of paclitaxel and rapamycin. Paclitaxel itself did not show any autophagic
      effect on cells but did show cell apoptosis by flow cytometry. Light chain 3, a
      microtubule-associated protein, which reflect autophagy, was increased with 5 nM
      of paclitaxel after pretreatment with 10 nM of rapamycin. CONCLUSION: These
      findings suggest that the autophagic inducer, rapamycin, can potentiate
      autophagic cell death when added as an apoptosis-inducing chemotherapeutic agent.
      In conclusion, the control of autophagy may be a future target for chemotherapy.

PMID- 24327987
TI  - The ON-Q pain management system in elective gynecology oncologic surgery:
      Management of postoperative surgical site pain compared to intravenous patient
      controlled analgesia.
AB  - OBJECTIVE: The goal of this study was to compare postoperative surgical site pain
      in gynecologic cancer patients who underwent elective extended lower midline
      laparotomy and managed their pain with either the ON-Q pain management system
      (surgical incision site pain relief system, ON-Q pump) or an intravenous patient
      controlled analgesia pump (IV PCA). METHODS: Twenty gynecologic cancer patients
      who underwent elective extended lower midline laparotomy were divided into two
      groups. One group received a 72-hour continuous wound perfusion of the local
      anesthetic ropivacaine (0.5%, study group) into the supraperitoneal layer of the
      abdominal incision through the ON-Q pump. The other group received intravenous
      infusion pump of patient-controlled analgesia (fentanyl citrate 20 mg/mL .
      kg+ondansetron hydrochloride 16 mg/8 mL+normal saline). Postoperative pain was
      assessed immediately and at 6, 24, 48, 72, and 96 hours after surgery using the
      visual analogue scale. RESULTS: Postoperative surgical site pain scores at 24,
      48, and 72 hours after surgery were lower in the ON-Q group than the IV PCA
      group. Pain scores at 24 hours and 48 hours after surgery were significantly
      different between the two groups (P=0.023, P<0.001). Overall painkiller
      administration was higher in the ON-Q group but this difference was not
      statistically significant (5.1 vs. 4.3, P=0.481). CONCLUSION: This study revealed
      that the ON-Q pain management system is a more effective approach than IV PCA for
      acute postoperative surgical site pain relief after extended lower midline
      laparotomy in gynecologic cancer patients.

PMID- 24327988
TI  - Expression of CD44 in endometrial stromal cells from women with and without
      endometriosis and its effect on the adherence to peritoneal mesothelial cells.
AB  - OBJECTIVE: This study was performed to compare the expression of CD44 in
      endometrial stromal cells (ESCs) of women with and without endometriosis and to
      evaluate the role of CD44 in the adherence of ESCs to peritoneal mesothelial
      cells (PMCs). METHODS: A PMC adherence assay was performed to evaluate the
      adherence of ESCs to PMCs in women with and without endometriosis. The expression
      of CD44 mRNA was measured by reverse transcription-polymerase chain reaction.
      CD44 protein was evaluated by Western blot analysis. RESULTS: There were no
      significant differences in the expression of CD44 mRNA and protein in ESCs or in
      the binding of ESCs to PMCs between patients with endometriosis and controls.
      Although the expression of CD44 protein was decreased in both women with
      endometriosis and controls after anti-CD44 antibody treatment, there was no
      effect on binding of ESCs to PMCs. Treatment of ESCs with peritoneal fluid from
      endometriosis patients resulted in a significant increase in binding of ESCs to
      PMCs compared to untreated ESCs in the endometriosis group. CONCLUSION: This
      study demonstrates that the expression of CD44 protein in ESCs from women with
      endometriosis might not be directly associated with adherence to PMCs.

PMID- 24327989
TI  - Type-specific prevalence of high-risk human papillomavirus by cervical cytology
      and age: Data from the health check-ups of 7,014 Korean women.
AB  - OBJECTIVE: We investigated the type-specific high-risk human papillomavirus (HPV)
      prevalence and distribution according to cervical cytology and age in healthy
      Korean women. METHODS: A retrospective cross-sectional study was conducted with
      7,014 consecutive subjects undergoing both liquid-based cervical cytology and HPV
      genotyping test by DNA chip for cervical cancer screening. The type-specific
      prevalence and distribution of individual high-risk HPV types were assessed
      according to cervical cytology and age groups (<30, 30-39, 40-49, 50-59, and >=60
      years old). RESULTS: In total, the most common HPV genotype was HPV58 (23.9% of
      all high-risk HPV-positive subjects), followed by HPV16 (21.8%), HPV52 (16.6%),
      and HPV18 (11.7%). Regarding cervical cytology and age groups, the proportion of
      HPV56 strongly increased with the increasing severity of cervical cytology (P for
      trend=0.041). An age-specific decline in the overall high-risk HPV prevalence was
      reaffirmed, and the proportion of HPV52 declined markedly with age (P for
      trend=0.014). CONCLUSION: The type-specific prevalence of high-risk HPV types
      significantly varies according to cervical cytology and age. It may imply that
      these types have different to develop into precancerous lesions in normal cervix.

PMID- 24327990
TI  - Squamous cell carcinoma arising in an ovarian mature cystic teratoma complicating
      pregnancy.
AB  - Mature cystic teratomas of the ovary (MCT) are usually observed in women of
      reproductive age with the most dreadful complication being malignant
      transformation which occurs in approximately 1% to 3% of MCTs. In this case
      report, we present a patient with squamous cell carcinoma which developed from a
      MCT during pregnancy. The patient was treated conservatively without adjuvant
      chemotherapy and was followed without evidence of disease for more than 60 months
      using conventional tools as well as positron emission tomography-computed
      tomography following the initial surgery. We report this case along with the
      review of literature. 

PMID- 24327991
TI  - Multicystic benign mesothelioma of the pelvic peritoneum presenting as acute
      abdominal pain in a young woman.
AB  - Multicystic benign mesothelioma (MBM) of the peritoneum is a very rare condition.
      Since the first description of MBM in 1979, approximately 100 cases have been
      reported. This is a case report of MBM of the pelvic peritoneum presenting as
      acute abdominal pain in a young woman. Laparoscopy confirmed multiple grapelike
      clusters of cysts that originated in the peritoneum of the rectouterine pouch and
      histopathologic diagnosis was confirmed as MBM of the pelvic peritoneum. We hope
      to alert gynaecologists of the diagnostic and therapeutic approaches to MBM which
      can be accomplished by laparoscopy. 

PMID- 24327992
TI  - Temporary homonymous hemianopsia after epidural blood patch.
AB  - We describe a case in which homonymous hemianopsia developed abruptly following
      an epidural blood patch procedure. The procedure was performed in a patient
      complaining of post-dural puncture headache after an emergency Cesarean section
      under spinal anesthesia. Computed tomography and magnetic resonance imaging
      demonstrated that air bubbles had moved from the prepontine and premedullar
      cisterns toward the left retrochiasmal region. The homonymous hemianopsia
      resolved rapidly with conservative management including oxygen, intravenous
      fluid, and antibiotics. We report on this case with a brief review of the related
      literature. 

PMID- 24327993
TI  - Should advanced maternal age be a reasonable indication for invasive diagnostic
      testing?

PMID- 24327994
TI  - Dyslipidemia in women with polycystic ovary syndrome.
AB  - Dyslipidemia is a very common metabolic abnormality in women with polycystic
      ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus
      dyslipidemia in women with PCOS may be consistent with those found in an insulin
      resistant state. In recent meta-analysis, triglycerides and low-density
      lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high
      density lipoprotein cholesterol concentration was 6 mg/dL lower in women with
      PCOS than those of controls. Alterations in LDL quality also have been reported
      in women with PCOS: women with PCOS have an increased proportion of atherogenic
      small dense LDL or decreased mean LDL particle size. However, in a recent Korean
      study, non-obese Korean women with PCOS had no significant quantitative or
      qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been
      identified as an independent risk factor for coronary heart disease, and its
      elevation in PCOS patients has been consistently reported in diverse studies
      including non-obese Korean population. Some studies have investigated
      apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA
      I, which has cardio-protective effects, were significantly lower in women with
      PCOS than those of controls. ApoC-I is known to increase the postprandial serum
      lipid level that is common in coronary artery disease patients, and one study
      reported that such an elevation may be the earliest variation of lipid
      abnormality in women with PCOS. In conclusion, women with PCOS should receive a
      complete lipid test, and lifestyle modification, including diet and exercise, is
      the first line therapy for all women with PCOS and is particularly important for
      those with dyslipidemia. 

PMID- 24327996
TI  - Maternal age-specific rates of fetal chromosomal abnormalities in Korean pregnant
      women of advanced maternal age.
AB  - OBJECTIVE: To evaluate the association of maternal age with occurrence of fetal
      chromosomal abnormalities in Korean pregnant women of advanced maternal age
      (AMA). METHODS: A retrospective review of the amniocentesis or chorionic villous
      sampling (CVS) database at Gangnam and Bundang CHA Medical Centers, between
      January 2001 and February 2012, was conducted. This study analyzed the incidence
      of fetal chromosomal abnormalities according to maternal age and the correlation
      between maternal age and fetal chromosomal abnormalities in Korean pregnant women
      >=35 years of age. In addition, we compared the prevalence of fetal chromosomal
      abnormalities between women of AMA only and the others as the indication for
      amniocentesis or CVS. RESULTS: A total of 15,381 pregnant women were selected for
      this study. The incidence of aneuploidies increased exponentially with maternal
      age (P<0.0001). In particular, the risk of trisomy 21 (standard error [SE],
      0.0378; odds ratio, 1.177; P<0.001) and trisomy 18 (SE, 0.0583; odds ratio,
      1.182; P=0.0040) showed significant correlation with maternal age. Comparison
      between women of AMA only and the others as the indication for amniocentesis or
      CVS showed a significantly lower rate of fetal chromosomal abnormalities only in
      the AMA group, compared with the others (P<0.0001). CONCLUSION: This study
      demonstrates that AMA is no longer used as a threshold for determination of who
      is offered prenatal diagnosis, but is a common risk factor for fetal chromosomal
      abnormalities.

PMID- 24327997
TI  - The frequency and clinical significance of intra-amniotic inflammation defined as
      an elevated amniotic fluid matrix metalloproteinase-8 in patients with preterm
      labor and low amniotic fluid white blood cell counts.
AB  - OBJECTIVE: To determine the frequency and clinical significance of intra-amniotic
      inflammation (IAI) defined as an elevated amniotic fluid (AF) matrix
      metalloproteinase-8 (MMP-8) concentration in patients with preterm labor and
      intact membranes (PTL) and low AF white blood cell (WBC) counts. METHODS: Adverse
      pregnancy outcomes were compared according to the presence or absence of IAI in
      220 singleton gestations who underwent amniocentesis due to PTL (gestational
      age<35.7 weeks) and had low AF WBC counts (<19 cells/mm(3)). Adverse pregnancy
      outcomes included preterm birth within 5 days of amniocentesis, acute histologic
      chorioamnionitis (acute-HCA) and positive AF culture. IAI was defined as an
      elevated AF MMP-8 concentration (>=23 ng/mL). RESULTS: IAI was present in 19% of
      study population. Adverse pregnancy outcomes were significantly more frequent in
      patients with IAI than in those without IAI (preterm birth within 5 days of
      amniocentesis, 88% vs. 41%; acute-HCA, 47% vs. 11%; positive AF culture, 10% vs.
      2%; each for P<0.05). Patients with IAI had a significantly shorter median
      amniocentesis-to-delivery interval than those without IAI (7.8 hours [0.01
      3,307.3 hours] vs. 310.3 hours [0.01-2,973.8 hours]; P<0.001 from survival
      analysis). Multiple logistic regression analysis demonstrated that only an IAI
      (odds ratio, 3.3; 95% confidence interval, 1.5-7.3; P<0.005) retained a
      statistical significance in the prediction of acute-HCA after other confounding
      variables were adjusted. CONCLUSION: Approximately one-fifth of patients with PTL
      and low AF WBC counts have an evidence of IAI and are at risk for impending
      preterm delivery and acute-HCA when AF MMP-8 concentration is used.

PMID- 24327995
TI  - Breast diseases during pregnancy and lactation.
AB  - Breast is a typical female sexual physiologic organ that is influenced by steroid
      hormone from menarche until menopause. Therefore various diseases can be
      developed by continuous action of estrogen and progesterone. Breast diseases are
      mainly categorized as benign and malignant. It is very important to distinguish
      the malignancy from breast diseases. However, it is very difficult to diagnose
      malignancy in pregnant and lactating women even though the same breast diseases
      took place. Therefore, we will review breast diseases such as breast carcinoma
      during pregnancy and lactation. 

PMID- 24327998
TI  - Comparison of the efficacy of three once-weekly bisphosphonates on bone mineral
      density gains in Korean women.
AB  - OBJECTIVE: To assess the efficacies of once-weekly bisphosphonates on bone
      mineral density (BMD) gains in Korean women aged 50 years or more. METHODS: We
      selected 166 patients who received: alendronate 70 mg (n=48), alendronate 70 mg +
      cholecalciferol 2,800 IU (n=31) or risedronate 35 mg (n=87) for one year. The
      baseline BMD and the % changes of BMD at one-year were compared among the three
      medication groups. RESULTS: The menopausal status and number of women with
      osteoporosis was not different among the three groups, but mean age of women was
      significantly lower in alendronate group. Baseline BMD at L1-4 and femur neck
      (FN) was similar, but baseline BMD at femur total (FT) was significantly lower in
      alendronate group. After one-year use, the median % changes of BMD at three sites
      were similar among the three groups; however, the median values were highest in
      alendronate + cholecalciferol group (L1-4: 4.48%, 6.74%, and 4.50%; FT: 2.09%,
      3.70%, and 2.31%; FN: 3.05%, 3.79%, and 2.03%). CONCLUSION: Among three once
      weekly bisphosphonates, BMD gains were highest after one-year use of
      alendronate+cholecalciferol, although statistically not significant.

PMID- 24327999
TI  - Clinical outcomes of vitrified-thawed embryo transfer using a pull and cut straw
      method.
AB  - OBJECTIVE: To compare the clinical outcomes of patients with vitrified-thawed
      embryos transferred using either the 0.25 mL straw method and the pull and cut
      straw (PNC) method. To evaluate the clinical outcomes of patients with
      transferred embryos that underwent assisted hatching at the cleaved embryo (day
      3) or the blastocyst (day 5) stage. METHODS: The study population consisted of
      women who underwent vitrified-warmed embryo transfer between May 2000 and
      December 2011 and assisted hatching was performed after warming of embryos.
      Cycles of thawing between assisted hatching treated and non treated groups were
      compared for survival and pregnancy rates. RESULTS: The PNC vitrification method
      improved survival and pregnancy rates in partial lysed embryos. While assisted
      hatching did not affect the developmental and clinical pregnancy rates of the
      vitrified-warmed blastocyst group, it did increase the pregnancy rate of poor
      quality vitrified-warmed cleaved embryos. CONCLUSION: These results suggest that
      PNC may increase the number of clinical pregnancies via the vitrification of both
      cleaved embryos and blastocysts. In addition, selective assisted hatching
      treatment of embryos that show a poor prognosis after warming may increase the
      rate of clinical pregnancy.

PMID- 24328000
TI  - A case report of prenatally diagnosed tetrasomy 18p.
AB  - Tetrasomy 18p, one of the most commonly observed isochromosomes, consists of two
      copies of the p arms on chromosome 18[i(18p)]. It is known as a de novo
      occurrence of non-disjunction or centromeric mis-division during meiosis II in
      the vast majority of cases. It has a prevalence of 1/140,000-180,000 live births
      and affects both genders equally. A 28-year-old woman was referred at 33+2 weeks
      gestation to rule out fetal congenital heart disease. Her prenatal
      ultrasonography showed intrauterine growth retardation, cardiomegaly, and
      imperforate anus. Doppler ultrasonographic finding showed fetal anemia. Tetrasomy
      18p was confirmed by conventional karyotyping and fluorescence in situ
      hybridization. Because of its very low prevalence rate, only several cases of
      tetrasomy 18p has been reported worldwide and it has not yet been reported in
      Korea before. Therefore, we report a case of prenatally diagnosed tetrasomy 18p. 

PMID- 24328001
TI  - Conservative multidisciplinary management of placenta percreta following in vitro
      fertilization.
AB  - Placenta percreta is an extremely rare and the most severe form of placental
      invasion, that is associated with severe maternal morbidity and mortality. We
      report a case of nulliparous woman who underwent 10 cycles of in vitro
      fertilization (IVF) without any known risk factors. We conserved her uterus by
      spontaneous vaginal delivery, leaving the placenta in situ, pelvic arterial
      embolization, and primary resection of the remaining placental tissues. This case
      demonstrates that repetitive IVF is a possible risk factor for placental
      invasion, and that conservation of the uterus can be achieved in such cases using
      a multidisciplinary approach. 

PMID- 24328002
TI  - A case of successful salvage chemotherapy of recurrent ovarian sertoli-leydig
      cell tumor.
AB  - Sertoli-Leydig tumors tend to relapse early and due to their rarity, limited data
      are available regarding a role of chemotherapy in the management of Sertoli
      Leydig cell tumors. We present a case of recurrent ovarian Sertoli-Leydig cell
      tumor whose salvage treatment was successful with paclitaxel and carboplatin
      chemotherapy. 

PMID- 24328003
TI  - Primary malignant melanoma arising in a cystic teratoma.
AB  - The malignant transformation of a cystic teratoma is a rare event, occurring in
      about 0.2% to 1.8%. Primary malignant melanoma arising from the ovary is
      extremely rare. A primary melanoma in an ovarian cystic teratoma originates most
      frequently at the dermoepidermal junction, similar to a cutaneous melanoma.
      Though there are no standard adjuvant regimens for the treatment of primary
      malignant melanoma of the ovary. We present another case report of malignant
      melanoma developing in cystic teratoma. 

PMID- 24328004
TI  - Retained placenta accreta after a first-trimester abortion manifesting as an
      uterine mass.
AB  - Placenta accreta during the first trimester of pregnancy is rare. Only a few
      cases of placenta accreta manifesting as a uterine mass have been published. Most
      patients with placenta accreta present with vaginal bleeding during or after
      pregnancy. This report describes a patient with placenta accreta that caused
      vaginal bleeding three years after a first trimester abortion. The patient had
      regular menstruation for three years after the abortion. Initially endometrial
      cancer or a uterine myoma with degeneration was suspected. This is the first
      report of a placenta accreta detected as a uterine mass long after a first
      trimester abortion with delayed vaginal bleeding. 

PMID- 24328005
TI  - The role of placental indoleamine 2,3-dioxygenase in human pregnancy.
AB  - Munn et al. made a scientific observation of major biological importance. For the
      first time they showed that in the mammal the fetus does survive an immune attack
      mounted by the mother, and that the mechanism responsible for the survival
      depends on the fetus and placenta 'actively' defending itself from attack by
      maternal T cells by means of an enzyme indoleamine 2,3-dioxygenase (EC
      1.13.11.42) dependent localised depletion of L-tryptophan. These findings raise
      critical questions for disease and its prevention during human pregnancy.
      Specifically, the role of this mechanism (discovered in mouse) in the human, and
      the extent to which defective activation of this process is responsible for major
      clinical diseases are unknown. Therefore some key facts about this enzyme
      expressed in the human placenta have been studied in order to test whether Munn
      et al.'s findings in mouse are met for human pregnancy. This short review
      attempts to describe our experimental work on human placental indoleamine 2,3
      dioxygenase. 

PMID- 24328006
TI  - Technique of fetal echocardiography.
AB  - Congenital heart disease is the most common abnormality in the human fetus. Fetal
      echocardiography has been used to detect the majority of cardiac defects, and it
      is now part of the routine screening method for fetal evaluation. In this
      article, we present standard ultrasonographic views of the normal fetal heart
      obtained during the second trimester, first-trimester fetal echocardiography
      findings, and a modified myocardial performance index. 

PMID- 24328007
TI  - Which is more important for the intensity of intra-amniotic inflammation between
      total grade or involved anatomical region in preterm gestations with acute
      histologic chorioamnionitis?
AB  - OBJECTIVE: There is no data on which is more important for the intensity of intra
      amniotic inflammation (IAI) between total grade or involved anatomical region in
      acute histologic chorioamnionitis (acute-HCA) of preterm-gestations. The
      objective of current study is to examine this issue. METHODS: The intensity of
      IAI was measured by amniotic fluid (AF) white blood cell (WBC) count and matrix
      metalloproteinase-8 (MMP-8) concentration in 225 singleton preterm-gestations
      (<36 weeks) who had acute-HCA including chorio-decidua involvement and delivered
      within 5 days of amniocentesis. Acute-HCA was defined in the presence of acute
      inflammatory changes in each anatomical region (i.e., chorio-decidua, amnion or
      chorionic plate). Patients were divided into 6 groups according to total grade
      (i.e., 1-6) and the presence or absence of chorio-decidua restriction (i.e.,
      chorio-decidua restriction vs. extension beyond chorio-decidua) of acute-HCA.
      RESULTS: There was no significant difference in a median AF WBC and MMP-8 between
      the two groups (group-1, cases with total grade 1 vs. group-2, cases with total
      grade 2) among cases with chorio-decidua restriction (each for P>0.05) and
      between the four groups (group-3, cases with total grade 2 vs. group-4, cases
      with total grade 3 vs. group-5, cases with total grade 4 vs. group-6, cases with
      total grade 5-6) among cases with extension beyond chorio-decidua (each for
      P>0.05). However, group-3 (cases with extension beyond chorio-decidua) had a
      significantly higher median AF WBC and MMP-8 than group-2 (cases with chorio
      decidua restriction) among cases with total grade 2 (each for P<0.05).
      CONCLUSION: Involved anatomical region is more important than total grade for the
      intensity of IAI in acute-HCA of preterm-gestations.

PMID- 24328008
TI  - Clinical efficacy of serum human epididymis protein 4 as a diagnostic biomarker
      of ovarian cancer: A pilot study.
AB  - OBJECTIVE: To compare accuracy of serum human epididymis protein 4 (HE4) levels
      with cancer antigen 125 (CA-125) levels as biomarkers for ovarian cancer.
      METHODS: The study population included 94 Korean women, including 32 patients
      with a diagnosis of ovarian cancer and 62 patients with a diagnosis of benign
      ovarian tumor. All diagnoses were confirmed by histopathological analysis. Serum
      HE4 levels were assessed using an HE4 enzyme immunoassay, which were performed
      according to the manufacturer's instructions. Serum CA-125 levels were determined
      using a Modular analytics E170 module. RESULTS: The median serum CA-125 and HE4
      levels were significantly higher in patients with ovarian cancer than those with
      other benign tumors (CA-125, 394.1 U/mL vs. 22.7 U/mL; HE4, 56.7 pM vs. 18.5 pM;
      P < 0.05 in both). An additional comparison revealed that the patients with
      endometriosis had greater median serum CA-125 levels than those with other benign
      ovarian tumors (32.0 U/mL vs. 17.9 U/mL, P = 0.03). Conversely, the median serum
      HE4 levels were similar among the two benign ovarian tumor groups, with no
      statistically significant difference observed (19.0 pM vs. 18.2 pM, P = 0.49).
      The receiver operating characteristics curve analysis for the benign ovarian
      tumor and ovarian cancer patients showed that HE4 showed a greater area under the
      curve with borderline significance when compared with CA-125 in both groups (0.93
      vs. 0.85). CONCLUSION: Serum HE4 levels may not only allow for the detection of
      ovarian cancer, but also allow for better differentiation of cases of ovarian
      cancer versus other benign ovarian tumors compared with serum CA-125.

PMID- 24328009
TI  - Factors related to dysmenorrhea among Vietnamese and Vietnamese marriage
      immigrant women in South Korea.
AB  - OBJECTIVE: To find factors associated with dysmenorrhea, we surveyed the
      obstetric and gynecologic histories as well as socioeconomic factors of
      Vietnamese female residents in Can Tho (southern part of Vietnam) and Bavi
      (northern part of Vietnam) and Vietnamese female marriage immigrants living in
      South Korea. METHODS: From March 2010 to March 2011, 3,017 Vietnamese women aged
      17 to 42 years (mean, 25.5 years) were recruited. Socioeconomic factors as well
      as baseline characteristics, including gynecologic history and menstrual
      patterns, were collected using questionnaires. The relationships between these
      factors and dysmenorrhea were analyzed using chi-square test, independent t-test
      and logistic regression analysis. RESULTS: Dysmenorrhea was found in 58.8% of all
      women. The mean age and the age at menarche were younger in the women with
      dysmenorrhea. A longer duration of menstrual flow and severe menstrual volume
      increased the risk of dysmenorrhea. The prevalence of dysmenorrhea was lower in
      women who had experienced pregnancy, term delivery and breastfeeding. The
      prevalence of dysmenorrhea in Vietnamese women was also different according to
      their educational status. When participants were divided according to their
      religious preferences, atheist women showed a lower prevalence with 55%, and
      women who were religious had a higher prevalence of dysmenorrhea. The body mass
      index, menstrual cycle length, monthly income, and duration of residency in Korea
      were not related with the prevalence of dysmenorrhea. CONCLUSION: Socioeconomic
      factors as well as age, menstrual pattern and obstetric history were related with
      dysmenorrhea in Vietnamese women.

PMID- 24328010
TI  - Carotid intima-media thickness in mainly non-obese women with polycystic ovary
      syndrome and age-matched controls.
AB  - OBJECTIVE: Metabolic disturbances are well-recognized clinical features of
      polycystic ovary syndrome (PCOS). Carotid intima-media thickness (CIMT) has been
      widely used as a surrogate marker of atherosclerosis and cardiovascular disease
      (CVD). CIMT in women with PCOS has been investigated in many studies, but there
      has been only one report in the Korean population. The aim of the present study
      was to compare the presence of subclinical atherosclerosis in young untreated
      Korean women with PCOS and age-matched controls, specifically by measuring their
      CIMT. METHODS: CIMT was measured by one radiologist in 56 PCOS patients and 56
      controls. To compare the CIMT according to PCOS phenotypes, women with PCOS were
      divided into two subgroups according to the presence of hyperandrogenism.
      RESULTS: Although PCOS patients were more obese and had higher blood pressure and
      insulin resistance index than the age-matched controls, the CIMT was not
      different between the two groups (0.49 +/- 0.09 mm in PCOS patients vs. 0.50 +/-
      0.11 mm in controls, respectively, p = 0.562). When the CIMT in the control group
      was compared with hyperandrogenic and non-hyperandrogenic PCOS groups, also no
      significant differences were found. CONCLUSION: Despite the significant
      differences in some vascular risk factors between women with PCOS and controls,
      PCOS patients did not have a significantly higher CIMT (even in the
      hyperandrogenic subgroups). Although our study did not show the increased risk of
      subclinical atherosclerosis in PCOS patients, the role of CIMT continues to be
      investigated considering the importance of screening and monitoring CVD risk
      factors in women with PCOS.

PMID- 24328011
TI  - Association of nursing-documented ambulation with length of stay following total
      laparoscopic hysterectomy for benign gynecologic disease.
AB  - OBJECTIVE: The objective was to examine the association of postoperative physical
      activity with length of stay in patients who received total laparoscopic
      hysterectomy for benign gynecologic disease. METHODS: The case group was composed
      of 70 patients who entered a critical pathway for elective total laparoscopic
      hysterectomy from 2009 to 2012 and were discharged behind schedule. The control
      group was selected from patients who were discharged on schedule, and matched to
      cases using 1:3 ratio propensity score matching. We compared the number of
      nursing-documented ambulation of the case group with that of control group.
      RESULTS: Year of surgery, age, body mass index, endometriosis, systemic disease,
      previous abdominal surgery and current medication were well balanced between case
      and control groups. The number of patients with nursing-documented ambulation in
      case group (19%) was not different from that in control group (11%). CONCLUSION:
      Postoperative physical activity measured by nursing-documented ambulation was not
      associated with length of stay in patients who underwent an elective total
      laparoscopic hysterectomy for benign gynecologic diseases.

PMID- 24328012
TI  - Development of Purtscher-like retinopathy after pre-eclampsia combined with acute
      pancreatitis.
AB  - Visual disturbances are common among women with pre-eclampsia. The obstetricians
      should have an understanding of the various conditions associated with visual
      impairments. We report a case of Purtscher-like retinopathy developed after pre
      eclampsia combined with acute pancreatitis. A 33-year-old primigravida with twin
      pregnancy was admitted to the department of obstetrics and gynecology for preterm
      labor and pre-eclampsia at 36+4 weeks gestation. After a cesarean section, she
      complained of abdominal pain and visual acuity loss. She was diagnosed with
      Purtscher-like retinopathy combined with acute pancreatitis after ophthalmologic
      examination and an abdominal computed tomography scan. Purtscher-like
      retinopathy, most often observed after trauma, is very rare in pre-eclampsia. In
      addition, while visual disturbances from other conditions are transient, it can
      result in persistent visual impairments. Thus, when a patient with pre-eclampsia
      complains of visual problems for a long period of time, obstetricians should
      consider an ophthalmologic evaluation and treatments during the earliest stage of
      the disease. 

PMID- 24328013
TI  - Prune-belly syndrome detected by ultrasound in the first trimester and the
      usefulness of vesicocentesis as a modality of treatment.
AB  - Prune-belly syndrome may be related to lower urinary tract obstruction (LUTO).
      LUTO in the early gestational age exacerbates fetal renal function and may
      require intrauterine intervention. If early developed LUTO causes bladder
      distension and abdominal musculature deficiency, it will result in prune belly
      syndrome. Therefore, early detection of the disease and proper treatment before
      the renal impairment is important. However, there are few literatures concerning
      the treatment of prune belly syndrome in the first trimester. We report a case of
      prune belly syndrome diagnosed at 11+6 weeks of gestation and the value of
      vesicocentesis as a modality of treatment. Ultrasound showed dilated fetal
      bladder and vesicocentesis was successful in reducing the volume of the bladder.
      However, the pregnancy was terminated upon request. 

PMID- 24328014
TI  - Synchronous occurrence of primary malignant mixed mullerian tumor in ovary and
      uterus.
AB  - Malignant mixed mullerian tumor (MMMT) arising from female internal genitalia is
      rare with the uterine corpus being the most prevalently affected site. It is even
      more rare when it occurs on both uterus and ovary at the same time. We describe a
      case of synchronized occurrence of MMMT on ovary and uterine adenosarcoma with
      review of literature. 

PMID- 24328015
TI  - Pulmonary embolism and deep vein thrombosis related to oral contraceptive use.
AB  - Pulmonary embolism (PE) and deep vein thrombosis (DVT) is a serious medical
      problem causing considerable morbidity and mortality. Risk factors of thrombosis
      are surgery, trauma, pregnancy, tumor, oral contraceptive as well as genetic risk
      factors though genetic risk factors were found in about 5% to 10% of cases.
      Yasmin, a combined oral contraceptive containing ethinylestradiol 30 ug and
      drospirenon 3 mg was launched in the United Kingdom in 2002. We had experienced a
      patient, 24-year-old young woman with left inguinal pain on ambulation, and edema
      of left leg four months after taking Yasmin. We performed chest pulmonary
      angiography computed tomography (CT) and lower extremity venogram CT. She was
      diagnosed to PE in both lower lobes and DVT below the level of left external
      iliac vein, and treated by low molecular weight heparin and warfarin. We report
      this case with brief review of literatures. 

PMID- 24328016
TI  - Gynecologic complication of chronic graft-versus-host disease: Vaginal
      obstruction.
AB  - Allogenic peripheral blood stem cell transplantation (Allo-PBSCT) is being used
      to treat hematological malignancies with increasing frequency. Graft-versus-host
      disease (GvHD) is a complex complication of PBSCT. A 43-year-old woman came to
      the gynecology clinic for amenorrhea. She had been diagnosed with acute myeloid
      leukemia 2 years earlier and treated with induction and consolidation
      chemotherapy. After developing complete remission, she underwent Allo-PBSCT. When
      she started chemotherapy, her menstrual cycle completely disappeared. Fourteen
      months after menopausal hormone replacement therapy, it was discovered that her
      upper vaginal canal was completely obstructed. The lower vagina had an atrophic
      appearance. We report a rare case of partial vaginal obstruction as a
      complication of chronic GvHD and review the literature. We expect that this case
      report provides an opportunity to remind clinician of the gynecologic
      complications of GvHD. 

PMID- 24328017
TI  - Predictive value of preoperative serum CA-125 levels in patients with uterine
      cancer: The Asian experience 2000 to 2012.
AB  - OBJECTIVE: Much of the early investigative work on the usefulness of preoperative
      serum CA-125 levels in identifying patients with early-stage endometrial
      carcinoma who have occult metastases were carried out in Europe and the United
      States. This article reviews CA-125 as a possible index for determining the need
      for full surgical staging, from the results of large medical centers in Asia,
      particularly Taiwan and Korea. METHODS: A Medline search was performed using CA
      125 and endometrial cancer as index words from 1981 to 2012. Those publications
      felt to be the most important especially from institutions from Asia since 2000
      were identified in this review. RESULTS: Most articles that analyzed the utility
      of serum CA-125 levels as predictive marker for disease extent or prognosis in
      uterine cancer used univariate and multivariable logistic regression analysis,
      and performed receiver operative curves to find the best cut-off values. The main
      factor of interest was whether clinicians can stratify patients that need
      lymphadenectomy in early stage disease. Suggested optimal cut-off value ranged
      from 20 to 210 U/mL. Not only preoperative CA-125 level, but myometrial invasion
      status by magnetic resonance imaging was the most significant combined parameter
      for predicting disease extent. CONCLUSION: Elevated CA-125 in patients with
      apparent early-stage disease is clearly a risk factor for the presence of extra
      uterine disease although the optimal cut-off levels vary. The evolution of
      clinical investigations over the past decade, particularly in Asia, suggests
      employment of the test in a more focused manner to identify high risk patients
      preoperatively.

PMID- 24328019
TI  - A comparative study of methylergonovine and 15-methyl prostaglandin F2alpha in
      active management of third stage of labor.
AB  - OBJECTIVE: Postpartum hemorrhage is most common cause of maternal mortality.
      Active management of third stage of labor minimizes the risk of postpartum
      hemorrhage. To compare the effect of methylergonovine and 15-methyl prostaglandin
      F2alpha (15-methyl PGF2alpha) in active management of third stage of labor.
      METHODS: A randomized open labelled parallel study with 50 women in normal labor,
      25 in each group were included. The drugs methylergonovine (0.2 mg) intravenous
      and 15-methyl PGF2alpha (250 ug) intramuscular were administered at the time of
      delivery of anterior shoulder. Main outcomes measured were amount of blood loss
      during the first four hours of delivery and objective measurement of hemoglobin
      and hematocrit levels before delivery and third day postpartum. RESULTS: There
      was no statistically significant difference in the blood loss between the two
      groups at delivery (P = 0.130), at 1 hour of delivery (P = 0.453). The blood loss
      with 15-methyl PGF2alpha was significantly less as compared to that of blood loss
      with methylergonovine at four hours of delivery (P = 0.014) and the total, i.e.,
      during first four hours, amount of blood loss was significantly less with 15
      methyl PGF2alpha (P = 0.026). There was no statistically significant difference
      in the hemoglobin and hematocrit levels measured predelivery and postpartum third
      day between both the drugs. CONCLUSION: Both the drugs were effective in
      controlling the amount of blood loss during the third stage of labor, 15-methyl
      PGF2alpha being more efficacious.

PMID- 24328020
TI  - Simplified protocol of nuchal translucency measurement: Is it still effective?
AB  - OBJECTIVE: Nuchal translucency (NT) is the most powerful screening tool for Down
      syndrome and congenital cardiac anomaly, therefore strict guidelines were
      established to get accurate NT values. However, to stick to the guideline in all
      pregnant women is time-consuming and superfluous in majority of low risk
      population. We undertook this study to investigate whether the simplified
      protocol enables to select low risk group and is effective in them even if we
      skip the suggested NT measurement. METHODS: NT and crown-rump length (CRL) were
      measured prospectively. First, CRL was measured in the ordinary view that was mid
      sagittal section of fetus in neutral position, and NT was measured at the same
      frozen screen (first measured value, 1MV). Then, NT was measured again according
      to the Fetal Medicine Foundation (FMF) guideline (second measured value, 2MV).
      RESULTS: There was good correlation between 1MV and 2MV in each case (r = 0.83, P
      < 0.001). All of the NT values over the 95th percentile in 2MV also belonged to
      over the 95th percentile in 1MV. NT value of 2 mm in 1MV could be used as a cut
      off to obtain over the 95th percentile 2MV by receiver operating characteristic
      curve (sensitivity 100%, specificity 80.5%). The proportion of 1MV >= 2 mm was
      only 23.8% of all cases, namely we had only to measure 2MV in 23.8% patients.
      Every 95th percentile or more 2MV could be detected with this simplified
      protocol. CONCLUSION: If NT is less than 2 mm at ordinary CRL view, we may skip
      suggested NT measurement according to FMF guideline.

PMID- 24328018
TI  - Gynecologic malignancy in pregnancy.
AB  - Gynecologic malignancy during pregnancy is a stressful problem. For the diagnosis
      and treatment of malignancy during pregnancy, a multidisciplinary approach is
      needed. Patients should be advised about the benefits and risk of treatment. When
      selecting a treatment for malignancy during pregnancy, the physiologic changes
      that occur with the pregnancy should be considered. Various diagnostic procedures
      that do not harm the fetus can be used. Laparoscopic surgery or laparotomy may be
      safely performed. The staging approach and treatment should be standard. Systemic
      chemotherapy during the first trimester should be delayed if possible. Radiation
      therapy should preferably start postpartum. Although delivery should be delayed
      preferably until after 35 weeks of gestation, termination of pregnancy may be
      considered when immediate treatment is required. Subsequent pregnancies do not
      increase the risk of malignancy recurrence. 

PMID- 24328021
TI  - Three-dimensional volumetric gray-scale uterine cervix histogram prediction of
      days to delivery in full term pregnancy.
AB  - OBJECTIVE: Our aim was to figure out whether volumetric gray-scale histogram
      difference between anterior and posterior cervix can indicate the extent of
      cervical consistency. METHODS: We collected data of 95 patients who were
      appropriate for vaginal delivery with 36th to 37th weeks of gestational age from
      September 2010 to October 2011 in the Department of Obstetrics and Gynecology,
      Korea University Ansan Hospital. Patients were excluded who had one of the
      followings: Cesarean section, labor induction, premature rupture of membrane.
      Thirty-four patients were finally enrolled. The patients underwent evaluation of
      the cervix through Bishop score, cervical length, cervical volume, three
      dimensional (3D) cervical volumetric gray-scale histogram. The interval days from
      the cervix evaluation to the delivery day were counted. We compared to 3D
      cervical volumetric gray-scale histogram, Bishop score, cervical length, cervical
      volume with interval days from the evaluation of the cervix to the delivery.
      RESULTS: Gray-scale histogram difference between anterior and posterior cervix
      was significantly correlated to days to delivery. Its correlation coefficient (R)
      was 0.500 (P = 0.003). The cervical length was significantly related to the days
      to delivery. The correlation coefficient (R) and P-value between them were 0.421
      and 0.013. However, anterior lip histogram, posterior lip histogram, total
      cervical volume, Bishop score were not associated with days to delivery (P
      >0.05). CONCLUSION: By using gray-scale histogram difference between anterior and
      posterior cervix and cervical length correlated with the days to delivery. These
      methods can be utilized to better help predict a cervical consistency.

PMID- 24328022
TI  - The influence of serum substituents on serum-free Vero cell conditioned culture
      media manufactured from Dulbecco's modified Eagle medium in mouse embryo culture.
AB  - OBJECTIVE: This study was conducted to examine the influences of supplementation
      of the serum substituents and available period of serum-free Vero cell
      conditioned media (SF-VCM) manufactured from Dulbecco's modified Eagle medium
      cultured with Vero cells for in vitro development of mouse preimplantation
      embryos. METHODS: A total of 1,099 two-cell embryos collected from imprinting
      control region mice were cultured in SF-VCM with 10% and 20% human follicular
      fluid (hFF), serum substitute supplement (SSS), and serum protein substitute
      (SPS). Development of embryos was observed every 24 hours. Results between
      different groups were analyzed by chi-square test, and considered statistically
      significant when P-value was less than 0.05. RESULTS: The rates of embryonic
      development cultured in SF-VCM supplemented with serum substituents were
      significantly higher compare with serum-free group (P < 0.05). The rates of
      embryonic development after 48 hours (morula<=) and 96 hours (blastocyst<=) were
      significantly higher in 20% SSS and 10% SPS than in 20% hFF supplementation (P <
      0.05). And the rates of embryonic development after 96 hours (hatching
      blastocyst<=) were significantly higher in 10% SPS (94.5%) than in 20% SSS
      (82.6%) and 20% hFF supplementation (68.5%). The rates of embryonic development
      according to storage period of the SF-VCM supplemented with 10% SPS showed no
      significant difference between control, 2 weeks and 4 weeks group. However
      developmental rate in 6 weeks storage group was significantly lower than other
      groups. CONCLUSION: The rate of embryonic development after 96 hours (hatching
      blastocyst<=) was significantly higher in SF-VCM supplemented with 10% SPS. And
      storage period of media up to 4 weeks did not affect on embryonic development.

PMID- 24328023
TI  - Translation and linguistic validation of Korean version of short form of pelvic
      floor distress inventory-20, pelvic floor impact questionnaire-7.
AB  - The short forms of pelvic floor distress inventory (PFDI) and pelvic floor impact
      questionnaire (PFIQ) are useful disease specific questionnaires evaluating
      symptoms, quality of life for pelvic floor disorders. The purpose is to develop
      linguistic validation of the PFDI-20 and PFIQ-7 questionnaires. Three types of
      Korean version of questionnaires have been used in four locations of University
      Hospitals in Korea. Each version of questionnaires was developed by forward
      translation and back-translation by bilingual translators and was verified by the
      patients with pelvic floor disorder and healthy persons. For harmonization of 3
      types of questionnaires, four authors reviewed, discussed all discrepancies,
      incorporated and produced a new version. The multi-step processes of translation
      and linguistic validation of the Korean version of PFDI-20 and PFIQ-7
      questionnaire were completed. Further process of validation of Korean version of
      these questionnaires is required. 

PMID- 24328024
TI  - Failed transarterial embolization of subserosal uterine arteriovenous
      malformation.
AB  - Uterine arteriovenous malformation (AVM) is rare but potentially life-threatening
      from excessive vaginal bleeding. All uterine AVMs reported to date have been
      found in the endometrial or myometrial layers. Here we present a patient with a
      subserosal type AVM on the fundus of uterus, which spontaneously ruptured. 

PMID- 24328025
TI  - Liver recurrence in early endometrial cancer with focal myometrial invasion.
AB  - Endometrial cancer is the most common malignancy of the female genital tract. The
      cancer spreads by direct extension, transtubal dissemination, lymphatic
      dissemination, and/or by hematogenous spread, usually results in lung metastasis,
      but may less commonly involve liver, brain, and bone. Here, we describe a patient
      with stage IA endometrial cancer who developed liver recurrence 17 months after
      surgery. 

PMID- 24328026
TI  - Ovarian metastasis from pulmonary adenocarcinoma.
AB  - Metastatic ovarian cancer is not an uncommon finding. Such tumors almost always
      originate from female genital tract, colon, stomach, or breast. Lung cancer is
      not a common origin of ovarian metastases. Of all metastatic ovarian tumors,
      approximately 0.3% arise from lung cancer. Ovarian torsion is not an uncommon
      finding, but ovarian torsion with cancer is rare. Here, we report a 44-year-old
      woman who was previously diagnosed with advanced stage lung cancer and who
      emergently visited our hospital for abdominal pain. An imaging work-up revealed,
      ovarian torsion and exploratory laparotomy was performed. Pathological
      examination led to the diagnosis ovarian metastasis from lung cancer. This is the
      first case of ovarian metastasis from lung cancer, ovarian torsion. 

PMID- 24328027
TI  - Primary extraskeletal mesenchymal chondrosarcoma of the vulva.
AB  - Extraskeletal chondrosarcoma is rare, making up only 1% of reported
      chondrosarcoma. We experienced 3 cases of extraskeletal chondrosarcoma,
      especially in vulva. They were suspected as lipoma of the vulva. The patients had
      noticed a small but growing mass on their vulva which had been palpated earlier.
      The masses were excised with a 2 cm resection margin. The final pathological
      reports confirmed extraskeletal mesenchymal chondrosarcoma (EMC) of the vulva
      revealing no microscopic lesions on the resection margins. After 24 months of
      following from the initial diagnosis, the patients remain without evidence of any
      recurrent. Management of EMC is not well studied due to the rare and variable
      nature of the disease. However, the surgery, such as we had, is the mainstay of
      local treatment with studies showing better survival in patients who undergo wide
      surgical resection. The establishment of adjuvant systemic pharmacotherapy could
      be expected in the future. 

PMID- 24328028
TI  - Angiomyofibroblastoma of the vulva.
AB  - Angiomyofibroblastoma (AMFB) is an uncommon benign mesenchymal tumor. AMFB occurs
      almost in the vulvo-vaginal area of women. The gross features of AMFB are well
      circumscribed so it clinically is often thought as Bartholin gland cyst or
      aggressive angiomyxoma. Usually, most tumors grow slowly, and patients do not
      feel pain. It also has low tendency for local recurrence. The histologic findings
      of the tumors are abundant thin-walled blood vessels with hypocellular and
      hypercellular areas. Almost all tumor cells have immunoreactivity for both desmin
      and vimentin. It also has estrogen and/or progesterone receptors, but staining
      for cytokeratin is negative. Here is a case of AMFB of the vulva occurring in a
      40-year-old woman, involving the right labia majora. The patient described that
      her vulva mass grew in about few months. The maximum dimension of the tumor was
      measured as 2 cm, and we resected the tumor one month after as her second visit. 

PMID- 24328029
TI  - Identification of Cassava MicroRNAs under Abiotic Stress.
AB  - The study of microRNAs (miRNAs) in plants has gained significant attention in
      recent years due to their regulatory role during development and in response to
      biotic and abiotic stresses. Although cassava (Manihot esculenta Crantz) is
      tolerant to drought and other adverse conditions, most cassava miRNAs have been
      predicted using bioinformatics alone or through sequencing of plants challenged
      by biotic stress. Here, we use high-throughput sequencing and different
      bioinformatics methods to identify potential cassava miRNAs expressed in
      different tissues subject to heat and drought conditions. We identified 60 miRNAs
      conserved in other plant species and 821 potential cassava-specific miRNAs. We
      also predicted 134 and 1002 potential target genes for these two sets of
      sequences. Using real time PCR, we verified the condition-specific expression of
      5 cassava small RNAs relative to a non-stress control. We also found, using
      publicly available expression data, a significantly lower expression of the
      predicted target genes of conserved and nonconserved miRNAs under drought stress
      compared to other cassava genes. Gene Ontology enrichment analysis along with
      condition specific expression of predicted miRNA targets, allowed us to identify
      several interesting miRNAs which may play a role in stress-induced
      posttranscriptional regulation in cassava and other plants. 

PMID- 24328030
TI  - Chronic traumatic encephalopathy and suicide: a systematic review.
AB  - Traumatic brain injury (TBI) is a global health concern, and the recent
      literature reports that a single mild TBI can result in chronic traumatic
      encephalopathy (CTE). It has been suggested that CTE may lead to death by
      suicide, raising important prevention, treatment, and policy implications. Thus,
      we conducted a systematic review of the medical literature to answer the key
      question: What is the existing evidence in support of a relationship between CTE
      and suicide? Systematic searches of CTE and suicide yielded 85 unique abstracts.
      Seven articles were identified for full text review. Only two case series met
      inclusion criteria and included autopsies from 17 unique cases, 5 of whom died by
      suicide. Neither studies used blinding, control cases, or systematic data
      collection regarding TBI exposure and/or medical/neuropsychiatric history. The
      identified CTE literature revealed divergent opinions regarding neuropathological
      elements of CTE and heterogeneity regarding clinical manifestations. Overall
      quality of evidence regarding a relationship between CTE and suicide was rated as
      very low using Grading of Recommendations Assessment, Development and Evaluation
      Working Group (GRADE) criteria. Further studies of higher quality and
      methodological rigor are needed to determine the existence and nature of any
      relationship between CTE and suicide. 

PMID- 24328031
TI  - Comparison of a Bayesian network with a logistic regression model to forecast IgA
      nephropathy.
AB  - Models are increasingly used in clinical practice to improve the accuracy of
      diagnosis. The aim of our work was to compare a Bayesian network to logistic
      regression to forecast IgA nephropathy (IgAN) from simple clinical and biological
      criteria. Retrospectively, we pooled the results of all biopsies (n = 155)
      performed by nephrologists in a specialist clinical facility between 2002 and
      2009. Two groups were constituted at random. The first subgroup was used to
      determine the parameters of the models adjusted to data by logistic regression or
      Bayesian network, and the second was used to compare the performances of the
      models using receiver operating characteristics (ROC) curves. IgAN was found (on
      pathology) in 44 patients. Areas under the ROC curves provided by both methods
      were highly significant but not different from each other. Based on the highest
      Youden indices, sensitivity reached (100% versus 67%) and specificity (73% versus
      95%) using the Bayesian network and logistic regression, respectively. A Bayesian
      network is at least as efficient as logistic regression to estimate the
      probability of a patient suffering IgAN, using simple clinical and biological
      data obtained during consultation. 

PMID- 24328033
TI  - Multivalent hydrazide-functionalized magnetic nanoparticles for glycopeptide
      enrichment and identification.
AB  - Among the common approaches for global glycopeptide enrichment, hydrazide
      chemistry is well recognized. However, conventional hydrazide-functionalized
      products are composed of a single layer of hydrazide functional groups. Due to
      the limited specific surface area of such a structure, the loading amount of
      hydrazide groups immobilized on these materials is restricted. Therefore, these
      materials can only provide a limited reaction rate with glycopeptides in complex
      protein samples, which is exacerbated by the microheterogeneities of
      glycosylation. Here, we introduce a new functionalized magnetic nanoparticle
      coating with hydrazide-modified non-crosslinked polymer chains. The multivalent
      hydrazide-functionalized particles were synthesized by the surface-initiated atom
      transfer radical polymerization (SI-ATRP) technique. The density of the hydrazide
      groups on the surface of these nanoparticles was three-fold higher than that of
      conventional single-layered materials. The new particles enabled the highly
      sensitive and selective enrichment of glycopeptides from a digestion mixture of
      fetuin, even from a background mixture of non-glycosylated protein that was 100
      fold more abundant. The recovery ratio of glycopeptides was determined to be
      77.8%, and the glycopeptide binding capacity of the materials was determined to
      be 25 MUg mg(-1). Finally, the novel multivalent hydrazide-functionalized
      particles were applied in the enrichment of N-linked glycopeptides from mouse
      liver tissues, which resulted in the assignment of 511 unique glycopeptides
      belonging to 372 different glycoproteins. The results further demonstrated the
      potential of the multivalent particles for glycopeptide enrichment in complex
      proteomics samples. 

PMID- 24328032
TI  - DeGNServer: deciphering genome-scale gene networks through high performance
      reverse engineering analysis.
AB  - Analysis of genome-scale gene networks (GNs) using large-scale gene expression
      data provides unprecedented opportunities to uncover gene interactions and
      regulatory networks involved in various biological processes and developmental
      programs, leading to accelerated discovery of novel knowledge of various
      biological processes, pathways and systems. The widely used context likelihood of
      relatedness (CLR) method based on the mutual information (MI) for scoring the
      similarity of gene pairs is one of the accurate methods currently available for
      inferring GNs. However, the MI-based reverse engineering method can achieve
      satisfactory performance only when sample size exceeds one hundred. This in turn
      limits their applications for GN construction from expression data set with small
      sample size. We developed a high performance web server, DeGNServer, to reverse
      engineering and decipher genome-scale networks. It extended the CLR method by
      integration of different correlation methods that are suitable for analyzing data
      sets ranging from moderate to large scale such as expression profiles with tens
      to hundreds of microarray hybridizations, and implemented all analysis algorithms
      using parallel computing techniques to infer gene-gene association at
      extraordinary speed. In addition, we integrated the SNBuilder and GeNa algorithms
      for subnetwork extraction and functional module discovery. DeGNServer is publicly
      and freely available online. 

PMID- 24328035
TI  - Retraction notice to Interprofessional learning in acute care: developing a
      theoretical framework.

PMID- 24328034
TI  - CD43 signals prepare human T cells to receive cytokine differentiation signals.
AB  - T cells are increasingly used for passive immunotherapy and bone marrow
      transplantation. Proper ex-vivo management of the cells is important for the
      desired therapeutic effects. For differentiation into effector cells of the Th1
      and Th2 phenotypes, T-cells require signals from IFNgamma and IL-4, respectively.
      Naive cells have an extremely low expression of the specific receptors that
      recognize these cytokines, indicating that in order to differentiate, cells need
      to perceive other signals that will enable them to sense the cytokine milieu.
      CD43 has been proposed as one of the molecules that make the initial contacts
      with antigen presenting cells. We report here that in cord blood, adult naive and
      total human T cells, CD43 signals induced the expression of both IFNgamma and IL
      4 receptors, mediate their capping, increased their signaling and augmented
      differentiation mediated by these receptors. CD43 signals also stimulated the
      expression of IFNgamma and in neonatal cells that of IL-4 as well. These data
      demonstrate an important role for CD43 signals in T-cell preparedness for
      differentiation into effector cells.

PMID- 24328037
TI  - Endohedral metallofullerenes based on spherical I(h)-C(80) cage: molecular
      structures and paramagnetic properties.
AB  - Fullerenes are carbon cages assembled from fused hexagons andpentagons that have
      closed networks and conjugated pi systems. The curve of the fullerene structure
      requires that the constituent carbon atoms take on a pyramidal shape and produces
      extra strain energy. However, the highly symmetrical geometry of the fullerene
      decreases the surface tension in these structures, so highly symmetrical
      fullerenes are usually very stable. For example, C60 with icosahedral symmetry
      (Ih) is the most stable fullerene molecule. However, another highly symmetrical
      fullerene, Ih-C80, is extremely unstable. The reason for this difference is the
      open-shell electronic structure of Ih-C80, which has a 4-fold degenerate HOMO
      occupied by only two electrons. Predictably, once the degenerate HOMO of Ih-C80
      accepts six more electrons, it forms a closed-shell electronic structure similar
      to Ih-C60 and with comparable stability. Because the hollow structure of
      fullerenes can encapsulate metal atoms and those internal metals can transfer
      electrons to the fullerene cage, the encapsulation of metal clusters may provide
      an ideal technique for the stabilization of the Ih-C80 fullerenes. In this
      Account, we focus on the molecular structures and paramagnetic properties of
      spherical Ih-C80 endohedral fullerenes encaging a variety of metal moieties, such
      as metal atoms (Mn), metal nitride (M3N), metal carbide (MnC2), metal
      carbonitride (M3CN), and metal oxides (M4Om). We introduce several types of
      endohedral metallofullerenes such as Sc4C2@Ih-C80, which exhibits a Russian-doll
      like structure, and Sc3CN@Ih-C80, which encapsulates a planar metal carbonitride
      cluster. In addition, we emphasize the paramagnetic properties of Ih-C80-based
      metallofullerenes, such as Sc3C2@Ih-C80, Y2@C79N, and M3N@Ih-C80, to show how
      those spin-active species can present a controllable paramagnetism. This Account
      highlights an inspiring molecular world within the spherical Ih-C80 cages of
      various metallofullerenes. 

PMID- 24328036
TI  - Generation now: the new era of leadership.

PMID- 24328038
TI  - Hybrid gold/chiral Bronsted acid relay catalysis allows an enantioselective
      synthesis of (-)-5-epi-eupomatilone-6.
AB  - An enantioselective synthesis of (-)-5-epi-eupomatilone-6 has been accomplished
      by using relay catalytic cascade intramolecular hydrosiloxylation and Mukaiyama
      aldol reaction of 2,3,4-trimethoxy-6-(phenylethynyl)phenyl dimethylsilanol with
      fluorenylglyoxylate. 

PMID- 24328039
TI  - Effect of low-dose cadmium exposure on DNA methylation in the endangered European
      eel.
AB  - There is increasing evidence that epigenetics can play a key role in the etiology
      of diseases engendered by chronic pollutant exposure. Although epigenetics has
      received significant attention in the field of biomedicine during the last years,
      epigenetics research is surprisingly very limited in ecotoxicology. The aim of
      the present study was to investigate the possible effects of low-dose cadmium
      exposure on the DNA methylation profile in a critically endangered fish species,
      the European eel. Eels were exposed to environmentally realistic concentrations
      of cadmium (0.4 and 4 MUg.L(-1)) during 45 days. The global CpG methylation
      status of eel liver was determined by means of a homemade ELISA assay. We then
      used a methylation-sensitive arbitrarily primed PCR method to identify genes that
      are differentially methylated between control and Cd-exposed eels. Our results
      show that cadmium exposure is associated with DNA hypermethylation and with a
      decrease in total RNA synthesis. Among hypermethylated sequences identified,
      several fragments presented high homologies with genes encoding for proteins
      involved in intracellular trafficking, lipid biosynthesis, and phosphatidic acid
      signaling pathway. In addition, few fragments presented high homologies with
      retrotransposon-like sequences. Our study illustrates how DNA methylation can be
      involved in the chronic stress response to Cd in fish. 

PMID- 24328041
TI  - 1,5-Rhodium shift in rearrangement of N-arenesulfonylazetidin-3-ols into
      benzosultams.
AB  - Benzosultams are synthesized in an enantiopure form starting from alpha-amino
      acids through a rhodium-catalyzed rearrangement reaction of N
      arenesulfonylazetidin-3-ols. Mechanistically, this reaction involves C-C bond
      cleavage by beta-carbon elimination and C-H bond cleavage by a 1,5-rhodium shift.

PMID- 24328040
TI  - Allosteric regulation in phosphofructokinase from the extreme thermophile Thermus
      thermophilus.
AB  - An investigation into the kinetics and regulatory properties of the type-1
      phosphofructokinase (PFK) from the extreme thermophile Thermus thermophilus
      (TtPFK) reveals an enzyme that is inhibited by PEP and activated by ADP by
      modifying the affinity exhibited for the substrate fructose 6-phosphate (Fru-6-P)
      in a manner analogous to other prokaryotic PFKs. However, TtPFK binds both of
      these allosteric ligands significantly more tightly than other bacterial PFKs
      while effecting a substantially more modest extent of inhibition or activation at
      25  degrees C, reinforcing the principle that binding affinity and effectiveness
      can be both independent and uncorrelated to one another. These properties have
      allowed us to establish rigorously that PEP only inhibits by antagonizing the
      binding of Fru-6-P and not by influencing turnover, a conclusion that requires
      kcat to be determined under conditions in which both inhibitor and substrate are
      saturating simultaneously. In addition, the temperature dependence of the
      allosteric effects on Fru-6-P binding indicate that the coupling free energies
      are entropy-dominated, as observed previously for PFK from Bacillus
      stearothermophilus but not for PFK from Escherichia coli , supporting the
      hypothesis that entropy-dominated allosteric effects may be a characteristic of
      enzymes derived from thermostable organisms. For such enzymes, the root cause of
      the allosteric effect may not be easily discerned from static structural
      information such as that obtained from X-ray crystallography. 

PMID- 24328042
TI  - Multidimensional open-frameworks: combinations of one-dimensional channels and
      two-dimensional layers in novel BI/M oxo-chlorides.
AB  - Here we discuss the synthesis and characterization of three novel bismuth oxo
      chlorides ([Bi6Na0.5O7.5][Na0.5Cl3]channel[Cl]layer;
      [Bi17PbO22][Cl6]channel[Cl3]layer; [Bi9(Pb0.2Mn0.8)O12][Cl3]channel [Cl2]layer)
      which all show an original multidimensional crystal structure. It is formed of
      two-dimensional (2D)-layered blocks separated by Cl(-) layers. The blocks are
      porous with triangular one-dimensional (1D)-Cl(-) channels with various section
      sizes. This multidimensional feature is unique in the field of Bi and Pb oxo
      halides, while so far only 1D or 2D halides units have been reported. The
      stability of the framework is allowed by Bi(3+)/M(n+) aliovalent substitution to
      balance charge neutrality. The channel and tunnel walls are formed by edge
      sharing O(Bi,M)4 oxocentered tetrahedra, while the triangular tunnel junctions
      are achieved by O(Bi,M)5 pyramids. The three compounds are rather stable, but
      only [Bi6Na0.5O7.5][Na0.5Cl3]tunnel[Cl]layer was obtain as a single-phase
      material so that its photoluminecence properties have been investigated. It shows
      an unusual red bright luminescence with a maximum at 14150 cm(-1) at low
      temperatures due to Bi(3+) transitions that are well explained by the Bi-Cl
      bonding scheme. 

PMID- 24328043
TI  - Different insight into amphiphilic PEG-PLA copolymers: influence of
      macromolecular architecture on the micelle formation and cellular uptake.
AB  - One constrain in the use of micellar carriers as drug delivery systems (DDSs) is
      their low stability in aqueous solution. In this study "tree-shaped" copolymers
      of general formula mPEG-(PLA)n (n = 1, 2 or 4; mPEG = poly(ethylene glycol)
      monomethylether 2K or 5K Da; PLA = atactic or isotactic poly(lactide)) were
      synthesized to evaluate the architecture and chemical composition effect on the
      micelles formation and stability. Copolymers with mPEG/PLA ratio of about 1:1
      wt/wt were obtained using a "core-first" synthetic route. Dynamic Light
      Scattering (DLS), Field Emission Scanning Electron Microscopy (FESEM), and Zeta
      Potential measurements showed that mPEG2K-(PD,LLA)2 copolymer, characterized by
      mPEG chain of 2000 Da and two blocks of atactic PLA, was able to form
      monodisperse and stable micelles. To analyze the interaction among micelles and
      tumor cells, FITC conjugated mPEG-(PLA)n were synthesized. The derived micelles
      were tested on two, histological different, tumor cell lines: HEK293t and HeLa
      cells. Fluorescence Activated Cells Sorter (FACS) analysis showed that the FITC
      conjugated mPEG2K-(PD,LLA)2 copolymer stain tumor cells with high efficiency. Our
      data demonstrate that both PEG size and PLA structure control the biological
      interaction between the micelles and biological systems. Moreover, using confocal
      microscopy analysis, the staining of tumor cells obtained after incubation with
      mPEG2K-(PD,LLA)2 was shown to be localized inside the tumor cells. Indeed, the
      mPEG2K-(PD,LLA)2 paclitaxel-loaded micelles mediate a potent antitumor
      cytotoxicity effect. 

PMID- 24328044
TI  - Cu-BTC/aminated graphite oxide composites as high-efficiency CO2 capture media.
AB  - CO2 adsorption isotherms on Cu-BTC/aminated graphite oxide composites were
      measured in the pressure range up to 1.5 MPa at three different temperatures
      close to ambient. Adsorption capacity, isosteric heat of adsorption, and
      regenerability were investigated. They are considered as significant factors
      determining the practical application of materials for CO2 capture. The results
      indicate a significant improvement in the performance of the composites as CO2
      adsorbents in comparison with the parent Cu-BTC MOF. Among all samples analyzed,
      the composite of Cu-BTC and modified graphite oxide with the highest N content
      (MOF/GO-U3) is the best performing sample. On its surface 13.41 mmol/g CO2 was
      adsorbed at room temperature and 1.5 MPa. A high selectivity for CO2 adsorption
      over that of CH4 was found. The selectivities for CO2 adsorption over N2 are
      governed by the properties of the MOF phase. A relatively low heat of CO2
      adsorption and the high degree of surface homogeneity cause that the composites
      can be fully regenerated and used in multicycle adsorption with the minimum
      energy demand. 

PMID- 24328045
TI  - Modified halloysite nanotubes: nanoarchitectures for enhancing the capture of
      oils from vapor and liquid phases.
AB  - We prepared hybrid halloysite nanotubes (HNT/sodium alkanoates) in which the
      inner cavity of the nanoclay was selectively modified. Physicochemical studies
      evidenced the interactions between HNT and sodium alkanoates, ruled out clay
      exfoliation, quantified the amount of the loaded substance, and showed an
      increase of the total net negative charge, allowing us to obtain rather stable
      aqueous nanoclay dispersions. These dispersions were exploited as inorganic
      micelles to capture hydrocarbon and aromatic oils in the vapor and liquid states
      and were revealed to be nonfoaming but very efficient in encapsulating oils.
      Here, we have fabricated biocompatibile and low-cost inorganic micelles that can
      be exploited for industrial applications on a large scale. 

PMID- 24328046
TI  - Depletion flocculation induced by synergistic effects of nanoparticles and
      polymers.
AB  - The depletion flocculation of stable suspensions of charged microparticles (1.2
      MUm diameter polystyrene) by mixtures of silica nanoparticles (7 nm) and
      poly(acrylic) acid (PAA, Mn = 24 500) was studied. The experiments revealed a
      very clear critical flocculation concentration of PAA that was lowered by the
      addition of the silica nanoparticles. Equilibrium pair potentials between the
      particles, calculated from force profiles measured between a silica particle and
      plate using colloid probe atomic force microscopy, showed clear a synergistic
      effect in that the magnitude of the depletion and structural forces produced in
      the mixed PAA/nanoparticle system was significantly greater than the sum of the
      forces in systems containing only PAA or only nanoparticles. This effect arises
      from adsorption of the PAA onto the nanoparticles, creating much larger charged
      complexes. Comparing the calculated pair potentials to the observed flocculation
      results revealed that flocculation occurred once the magnitude of the secondary
      energy well formed by the attractive depletion force exceeded 5 kT. 

PMID- 24328048
TI  - Anisotropic Mo2-phthalocyanine sheet: a new member of the organometallic family.
AB  - Metal-organic porous sheets, due to their unique atomic configurations and
      properties, represent a class of materials beyond graphene and BN monolayers. The
      Mo2-phthalocyanine-based sheet (Mo2Pc) is a new member of this porous
      organometallic family. Using density functional theory with hybrid functional for
      exchange-correlation potential, we show that this dimer-based material, unlike
      conventional organic monolayers that contain isolated metal atoms, possesses
      unique mechanical, magnetic, electronic, and optical properties due to inherent
      anisotropy in the structure. Furthermore, it is a semiconductor with a direct
      band gap of 0.93 eV and is antiferromagnetic with each Mo site carrying a
      magnetic moment of 0.88 MUB. The strong anisotropy in elasticity and infrared
      light absorption is likely to open new doors for potential applications. 

PMID- 24328047
TI  - Cyclic RGD peptide incorporation on phage major coat proteins for improved
      internalization by HeLa cells.
AB  - Delivering therapeutic materials or imaging reagents into specific tumor tissues
      is critically important for development of novel cancer therapeutics and
      diagnostics. Genetically engineered phages possess promising structural features
      to develop cancer therapeutic materials. For cancer targeting purposes, we
      developed a novel engineered phage that expressed cyclic RGD (cRGD) peptides on
      the pVIII major coat protein using recombinant DNA technology. Using a type 88
      phage engineering approach, which inserts a new gene to express additional major
      coat protein in the noncoding region of the phage genome, we incorporated an
      additional pVIII major coat protein with relatively bulky cRGD and assembled
      heterogeneous major coat proteins on the F88.4 phage surfaces. With IPTG control,
      we could tune different numbers of cRGD peptide displayed on the phage particles
      up to 140 copies. The resulting phage with cRGD on the recombinant pVIII protein
      exhibited enhanced internalization efficiency into HeLa cells in a ligand density
      and conformational structure dependent manner when comparing with the M13 phages
      modified with either linear RGD on pVIII or cRGD on pIII. Our cRGD peptide
      engineered phage could be useful for cancer therapy or diagnostic purposes after
      further modifying the phage with drug molecules or contrast reagents in the
      future. 

PMID- 24328049
TI  - ON-OFF mechanism of a fluorescent sensor for the detection of Zn(II), Cd(II), and
      Cu(II)transition metal ions.
AB  - An ab initio multiconfigurational (CASPT2//CASSCF) approach has been employed to
      map radiative and nonradiative relaxation pathways for a cyclam
      methylbenzimidazole fluorescent sensor and its metal ion (Zn(2+), Cd(2+), and
      Cu(2+)) complexes to provide an universal understanding of ON-OFF fluorescent
      mechanisms for the selective identification of these metal ions. The photoinduced
      electron transfer (PET) between the receptor and the signaling unit is
      quantitatively attributed for the first time to a newly generated transition of
      S0->SCT((1)npi*), which is a typical (1)npi* excitation but exhibits a
      significant charge transfer character and zwitterionic radical configuration. The
      present study contributes the two theoretical models of the competitive
      coexistence of radiative/nonradiative decay channel in (1)pipi*/SCT((1)npi*)
      states for the detection of metal ions with d(10) configuration (i.e., Zn(2+),
      Cd(2+), etc.) and a downhill ladder relaxation pathway through multi nona
      diabatic relays for the probing of d(9) cations (Cu(2+), etc.). These
      computational results will establish a benchmark for ON-OFF mechanisms of a
      fluorescent sensor that coordinates various transition metal ions with different
      electron configuration and radius. 

PMID- 24328050
TI  - Vibrational and structural behavior of (L)-cysteine ethyl ester hydrochloride in
      the solid state and in aqueous solution.
AB  - The aim of this work is to evaluate the vibrational and structural properties of
      l-cysteine ethyl ester hydrochloride (CE), and its electronic behavior mainly in
      relation to the action of the thiol and amine groups at different degrees of
      solvation. The crystal structure of CE was determined at room temperature by X
      ray diffraction methods. Infrared and Raman spectra were collected to compare the
      behavior of different functional groups in the molecule, both in the solid phase
      and in aqueous solution. Its UV and circular dichroism spectra were also measured
      in aqueous solution. The influence of an aqueous environment on the CE spectra
      was simulated by means of implicit (polarizable continuum model) and explicit
      (molecular dynamics, solute-solvent clusters) methods. Calculations in explicit
      and continuous solvent are of interest to explain the behavior of bioavailable
      sites in this medium. The study was completed by natural bond orbital analysis to
      determine the presence of hyperconjugative interactions. 

PMID- 24328051
TI  - Catalytic, enantioselective, intramolecular carbosulfenylation of olefins.
      Preparative and stereochemical aspects.
AB  - The first catalytic, enantioselective, intramolecular carbosulfenylation of
      isolated alkenes with aromatic nucleophiles is described. The combination of N
      phenylsulfenylphthalimide, a chiral selenophosphoramide derived from BINAM, and
      ethanesulfonic acid as a cocatalytic Bronsted acid induced an efficient and
      selective cyclofunctionalization of various alkenes (aliphatic and aromatic)
      tethered to a 3,4-methylenedioxyphenyl ring. Under these conditions, 6-phenylthio
      5,6,7,8-tetrahydronaphthalenes are formed diastereospecifically in good yields
      (50-92%) and high enantioselectivities (71:29-97:3 er). E-Alkenes reacted much
      more rapidly and with much higher selectivity than Z-alkenes, whereas electron
      rich alkenes reacted more rapidly but with comparable selectivity to electron
      neutral alkenes and electron-deficient alkenes. The Bronsted acid played a
      critical role in effecting reproducible enantioselectivity. A model for the
      origin of enantioselectivity and the dependence of rate and selectivity on alkene
      structure is proposed along with a rationale for the site selectivity in
      reactions with monoactivated arene nucleophiles. 

PMID- 24328052
TI  - Colloidal-sized metal-organic frameworks: synthesis and applications.
AB  - Colloidal metal-organic frameworks (CMOFs), nanoporous colloidal-sized crystals
      that are uniform in both size and polyhedral shape, are crystals composed of
      metal ions and organic bridging ligands, which can be used as building blocks for
      self-assembly in organic and aqueous liquids. They stand in contrast to
      conventional metal-organic frameworks (MOFs), which scientists normally study in
      the form of bulk crystalline powders. However, powder MOFs generally have random
      crystal size and shape and therefore do not possess either a definite mutual
      arrangement with adjacent particles or uniformity. CMOFs do have this quality,
      which can be important in vital uptake and release kinetics. In this Account, we
      present the diverse methods of synthesis, pore chemistry control, surface
      modification, and assembly techniques of CMOFs. In addition, we survey recent
      achievements and future applications in this emerging field. There is potential
      for a paradigm shift, away from using just bulk crystalline powders, towards
      using particles whose size and shape are regulated. The concept of colloidal MOFs
      takes into account that nanoporous MOFs, conventionally prepared in the form of
      bulk crystalline powders with random crystal size, shape, and orientation, may
      also form colloidal-sized objects with uniform size and morphology. Furthermore,
      the traditional MOF functions that depend on porosity present additional control
      over those MOF functions that depend on pore interactions. They also can enable
      controlled spatial arrangements between neighboring particles. To begin, we
      discuss progress regarding synthesis of MOF nano- and microcrystals whose crystal
      size and shape are well regulated. Next, we review the methods to modify the
      surfaces with dye molecules and polymers. Dyes are useful when seeking to observe
      nonluminescent CMOFs in situ by optical microscopy, while polymers are useful to
      tune their interparticle interactions. Third, we discuss criteria to assess the
      stability of CMOFs for various applications. In another section of this Account,
      we give examples of supracrystal assembly in liquid, on substrates, at
      interfaces, and under external electric fields. We end this Account with
      discussion of possible future developments, both conceptual and technological. 

PMID- 24328054
TI  - SABRE: ligand/structure-based virtual screening approach using consensus
      molecular-shape pattern recognition.
AB  - We present an efficient and rational ligand/structure shape-based virtual
      screening approach combining our previous ligand shape-based similarity SABRE
      (shape-approach-based routines enhanced) and the 3D shape of the receptor binding
      site. Our approach exploits the pharmacological preferences of a number of known
      active ligands to take advantage of the structural diversities and chemical
      similarities, using a linear combination of weighted molecular shape density.
      Furthermore, the algorithm generates a consensus molecular-shape pattern
      recognition that is used to filter and place the candidate structure into the
      binding pocket. The descriptor pool used to construct the consensus molecular
      shape pattern consists of four dimensional (4D) fingerprints generated from the
      distribution of conformer states available to a molecule and the 3D shapes of a
      set of active ligands computed using SABRE software. The virtual screening
      efficiency of SABRE was validated using the Database of Useful Decoys (DUD) and
      the filtered version (WOMBAT) of 10 DUD targets. The ligand/structure shape-based
      similarity SABRE algorithm outperforms several other widely used virtual
      screening methods which uses the data fusion of multiscreening tools (2D and 3D
      fingerprints) and demonstrates a superior early retrieval rate of active
      compounds (EF(0.1%) = 69.0% and EF(1%) = 98.7%) from a large size of ligand
      database (~95,000 structures). Therefore, our developed similarity approach can
      be of particular use for identifying active compounds that are similar to
      reference molecules and predicting activity against other targets
      (chemogenomics). An academic license of the SABRE program is available on
      request.

PMID- 24328055
TI  - Ferric chloride-catalyzed reaction of [60]fullerene with tert-butyl N-substituted
      carbamates: synthesis of oxazolidino[4,5:1,2][60]fullerenes.
AB  - The rare oxazolidinofullerenes have been prepared by the ferric chloride
      catalyzed reaction of [60]fullerene with various tert-butyl N-substituted
      carbamates via t-Bu-O bond cleavage and heteroannulation under mild conditions. A
      possible mechanism for the formation of oxazolidinofullerenes is proposed. 

PMID- 24328056
TI  - Two novel ternary dicopper(II) MU-guanazole complexes with aromatic amines
      strongly activated by quantum dots for DNA cleavage.
AB  - Two novel (MU-guanazole)-bridged binuclear copper(II) complexes with 1,10
      phenanthroline (phen) or 2,2'-bipyridine (bipy), [Cu2(MU-N2,N4
      Hdatrz)(phen)2(H2O)(NO3)4] (1) and [Cu2(MU-N1,N2-datrz)2(MU-OH2)(bipy)2](ClO4)2
      (2) (Hdatrz = 3,5-diamino-1,2,4-triazole = guanazole), have been prepared and
      characterized by X-ray diffraction, spectroscopy, and susceptibility
      measurements. Compounds 1 and 2 differ in the aromatic amine, which acts as a
      coligand, and in the Cu...Cu'-bridging system. Compound 1, which contains two
      mono-bridged copper ions, represents the first example of a discrete Cu-(NCN-trz)
      Cu' complex. Compound 2, with two triply bridged copper ions, is one of the few
      compounds featuring a Cu-[(NN-trz)2 + (O-aquo)]-Cu' unit. Both compounds display
      antiferromagnetic coupling but of different magnitude: J (MU2,4-triazole) = -52
      cm(-1) for 1 and J (MU1,2-triazolate) = -115 cm(-1) for 2. The DNA binding and
      cleavage properties of the two compounds have been investigated. Fluorescence,
      viscosimetry, and thermal denaturation studies reveal that both complexes have
      high affinity for DNA (1 > 2) and that only 1 acts as an intercalator. In the
      presence of a reducing agent like 3-mercaptopropionic acid, 1 produces
      significant oxidative DNA cleavage, whereas 2 is inactive. However, in the
      presence of very small quantities of micelles filled with core-shell CdSe-ZnS
      quantum dots (15 nM), 1 and 2 are considerably more active and become highly
      efficient nucleases as a result of the different possible mechanisms for
      promoting cooperative catalysis (metal-metal, metal-hydrogen bonding, metal
      intercalation, and metal-nanoparticle). Electrophoresis DNA-cleavage inhibition
      experiments, X-ray photoelectron spectroscopy studies, and fluorescence ethidium
      bromide displacement assays reveal that in these novel nucleases the QDs act as
      redox-active protein-like nanoparticle structures that bind to the DNA and
      deliver electrons to the copper(II) centers for the generation of Cu(I) and
      reactive oxygen species. 

PMID- 24328057
TI  - Encapsulation of strongly fluorescent carbon quantum dots in metal-organic
      frameworks for enhancing chemical sensing.
AB  - Novel highly fluorescent (FL) metal-organic frameworks (MOFs) have been
      synthesized by encapsulating branched poly-(ethylenimine)-capped carbon quantum
      dots (BPEI-CQDs) with a high FL quantum yield into the zeolitic imidazolate
      framework materials (ZIF-8). The as-synthesized FL-functionalized MOFs not only
      maintain an excellent FL activity and sensing selectivity derived from BPEI-CQDs
      but also can strongly and selectively accumulate target analytes due to the
      adsorption property of MOFs. The selective accumulation effect of MOFs can
      greatly amplify the sensing signal and specificity of the nanosized FL probe. The
      obtained BPEI-CQDs/ZIF-8 composites have been used to develop an ultrasensitive
      and highly selective sensor for Cu(2+) ion, with a wide response range (2-1000
      nM) and a very low detection limit (80 pM), and have been successfully applied in
      the detection of Cu(2+) ions in environmental water samples. It is envisioned
      that various MOFs incorporated with FL nanostructures with high FL quantum yields
      and excellent selectivity would be designed and synthesized in similar ways and
      could be applied in sensing target analytes. 

PMID- 24328058
TI  - Complementary strategies for developing Gd-free high-field T1 MRI contrast agents
      based on Mn(III) porphyrins.
AB  - Mn(III) porphyrin (MnP) holds the promise of addressing the emerging challenges
      associated with Gd-based clinical MRI contrast agents (CAs), namely, Gd-related
      adverse effect and decreasing sensitivity at high clinical magnetic fields. Two
      complementary strategies for developing new MnPs as Gd-free CAs with optimized
      biocompatibility were established to improve relaxivity or clearance rate. MnPs
      with distinct and tunable pharmacokinetic properties can consequently be
      constructed for different in vivo applications at clinical field of 3 T. 

PMID- 24328059
TI  - Click chemistry approach for imaging intracellular and intratissue distribution
      of curcumin and its nanoscale carrier.
AB  - This study was aimed at developing a fluorescence imaging approach to
      simultaneously characterize the delivery and distribution of a bioactive
      molecule, curcumin, and its micelle based nanoscale carrier in cells and tissue
      models. To enable imaging of curcumin, a monoalkyne derivative of curcumin was
      synthesized and purified using LC-MS. Intracellular uptake of curcumin was
      characterized using a click chemistry reaction between a monoalkyne modified
      curcumin and Alexa-488 azide fluorescent dye in cells and tissues. Fluorescence
      images of cells and tissues incubated with monoalkyne curcumin showed specific
      detection of intracellular delivered monoalkyne curcumin using the click
      chemistry reaction. The fluorescence imaging results also demonstrated
      significant improvement in detection sensitivity of intracellular delivered
      curcumin as compared to measurements based on native fluorescence of unmodified
      curcumin. Intracellular uptake of monoalkyne curcumin was characterized as a
      function of incubation time and concentration. The results show a rapid uptake of
      monoalkyne curcumin during the first 4 h of incubation. Modification of curcumin
      to its monoalkyne derivative did not impact its apoptotic activity in cancer
      cells. DSPE-PEG micelles labeled with Alexa-647 were selected as a representative
      nanoscale carrier to enhance the solubility and delivery of monoalkyne curcumin.
      Fluorescence images of cells and tissues incubated with fluorescently labeled
      micelles containing monoalkyne curcumin clearly illustrate significant
      differences in intracellular and intratissue localization of DSPE-PEG and
      encapsulated monoalkyne curcumin. The imaging approach developed in this study
      can be used to understand delivery and distribution of diverse bioactive
      compounds and their nanocarrier systems as well as in situ measurement of
      interactions of bioactives with cellular and tissue targets. 

PMID- 24328061
TI  - Ethanol and air quality: influence of fuel ethanol content on emissions and fuel
      economy of flexible fuel vehicles.
AB  - Engine-out and tailpipe emissions of NOx, CO, nonmethane hydrocarbons (NMHC),
      nonmethane organic gases (NMOG), total hydrocarbons (THC), methane, ethene,
      acetaldehyde, formaldehyde, ethanol, N2O, and NH3 from a 2006 model year Mercury
      Grand Marquis flexible fuel vehicle (FFV) operating on E0, E10, E20, E30, E40,
      E55, and E80 on a chassis dynamometer are reported. With increasing ethanol
      content in the fuel, the tailpipe emissions of ethanol, acetaldehyde,
      formaldehyde, methane, and ammonia increased; NOx and NMHC decreased; while CO,
      ethene, and N2O emissions were not discernibly affected. NMOG and THC emissions
      displayed a pronounced minimum with midlevel (E20-E40) ethanol blends; 25-35%
      lower than for E0 or E80. Emissions of NOx decreased by approximately 50% as the
      ethanol content increased from E0 to E30-E40, with no further decrease seen with
      E55 or E80. We demonstrate that emission trends from FFVs are explained by fuel
      chemistry and engine calibration effects. Fuel chemistry effects are fundamental
      in nature; the same trend of increased ethanol, acetaldehyde, formaldehyde, and
      CH4 emissions and decreased NMHC and benzene emissions are expected for all FFVs.
      Engine calibration effects are manufacturer and model specific; emission trends
      for NOx, THC, and NMOG will not be the same for all FFVs. Implications for air
      quality are discussed. 

PMID- 24328063
TI  - Throwing light on petroleum: simulated exposure of crude oil to sunlight and
      characterization using atmospheric pressure photoionization fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - The change in profile of crude oil following a release into the environment is a
      topic of significant interest, and there is a need to develop analytical
      methodologies for understanding natural processes which affect related complex
      mixture profiles. One such process is the exposure to sunlight. In the following
      investigation, three oil samples were studied: one served as a control, a second
      was subjected to irradiation by an ultraviolet lamp, and a third sample was
      irradiated by a SoLux light source which closely models the solar emission
      profile. The usage of the SoLux light source represents a new method which
      enables a controlled experiment to mimic the effects of sunlight upon the sample.
      Atmospheric pressure photoionization was selected as the primary ionization
      method due to the ability to ionize a broad range of compounds, including low
      polarity components which could not be observed using electrospray ionization.
      During a test of sample preparation methods, the addition of a protic cosolvent
      to the sample solutions was shown to broaden the range of heteroatom-containing
      components observed. Following characterization, it was found that the
      polyaromatic hydrocarbons did not change in profile, while compounds containing a
      heteroatom exhibited a tendency to oxidize following photoirradiation. Sulfur
      containing compounds with a low number of double bond equivalents were among the
      most reactive components of the complex mixture. The photooxidation of compounds
      in petroleum, following exposure to sunlight, is expected to have significance
      with regards to solubility and potential toxicity. 

PMID- 24328060
TI  - Flavonoids as therapeutic compounds targeting key proteins involved in
      Alzheimer's disease.
AB  - Alzheimer's disease is characterized by pathological aggregation of protein tau
      and amyloid-beta peptides, both of which are considered to be toxic to neurons.
      Naturally occurring dietary flavonoids have received considerable attention as
      alternative candidates for Alzheimer's therapy taking into account their
      antiamyloidogenic, antioxidative, and anti-inflammatory properties. Experimental
      evidence supports the hypothesis that certain flavonoids may protect against
      Alzheimer's disease in part by interfering with the generation and assembly of
      amyloid-beta peptides into neurotoxic oligomeric aggregates and also by reducing
      tau aggregation. Several mechanisms have been proposed for the ability of
      flavonoids to prevent the onset or to slow the progression of the disease. Some
      mechanisms include their interaction with important signaling pathways in the
      brain like the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein
      kinase pathways that regulate prosurvival transcription factors and gene
      expression. Other processes include the disruption of amyloid-beta aggregation
      and alterations in amyloid precursor protein processing through the inhibition of
      beta-secretase and/or activation of alpha-secretase, and inhibiting cyclin
      dependent kinase-5 and glycogen synthase kinase-3beta activation, preventing
      abnormal tau phosphorylation. The interaction of flavonoids with different
      signaling pathways put forward their therapeutic potential to prevent the onset
      and progression of Alzheimer's disease and to promote cognitive performance.
      Nevertheless, further studies are needed to give additional insight into the
      specific mechanisms by which flavonoids exert their potential neuroprotective
      actions in the brain of Alzheimer's disease patients. 

PMID- 24328062
TI  - Prion nucleation site unmasked by transient interaction with phospholipid
      cofactor.
AB  - Infectious mammalian prions can be formed de novo from purified recombinant prion
      protein (PrP) substrate through a pathway that requires the sequential addition
      of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and RNA cofactor
      molecules. Recent studies show that the initial interaction between PrP and POPG
      causes widespread and persistent conformational changes to form an insoluble
      intermediate species, termed PrP(Int1). Here, we characterize the mechanism and
      functional consequences of the interaction between POPG and PrP. Negative-stain
      electron microscopy of PrP(Int1) revealed the presence of amorphous aggregates.
      Pull-down and photoaffinity label experiments indicate that POPG induces the
      formation of a PrP(C) polybasic-domain-binding neoepitope within PrP(Int1). The
      ongoing presence of POPG is not required to maintain PrP(Int1) structure, as
      indicated by the absence of stoichiometric levels of POPG in solid-state NMR
      measurements of PrP(Int1). Together, these results show that a transient
      interaction with POPG cofactor unmasks a PrP(C) binding site, leading to
      PrP(Int1) aggregation. 

PMID- 24328064
TI  - Tribute to Michael D. Fayer.

PMID- 24328068
TI  - Publications of Michael D. Fayer.

PMID- 24328065
TI  - Biography of Michael D. Fayer.

PMID- 24328069
TI  - Two-stage statistical medium optimization for augmented cellulase production via
      solid-state fermentation by newly isolated Aspergillus niger HN-1 and application
      of crude cellulase consortium in hydrolysis of rice straw.
AB  - Cellulolytic enzyme production by newly isolated Aspergillus niger HN-1 was
      statistically optimized using Plackett-Burman and central composite design (CCD).
      Optimum concentrations of 2, 0.40, 0.01, and 0.60 g L (-1) for KH2PO4, urea,
      trace elements solution, and CaCl2.2H2O, respectively, were suggested by Design
      Expert software. The two-stage optimization process led to a 3- and 2-fold
      increases in the filter paper cellulase (FP) and beta-glucosidase activities,
      respectively. FP, beta-glucosidase, endoglucanase, exopolygalaturonase,
      cellobiohydrolase, xylanase, alpha-l-arabinofuranosidase, beta-xylosidase, and
      xylan esterase activities of 36.7 +/- 1.54 FPU gds(-1), 252.3 +/- 7.4 IU gds(-1),
      416.3 +/- 22.8 IU gds(-1), 111.2 +/- 5.4 IU gds(-1), 8.9 +/- 0.50 IU gds(-1),
      2593.5 +/- 78.9 IU gds(-1), 79.4 +/- 4.3 IU gds(-1), 180.8 +/- 9.3 IU gds(-1),
      and 288.7 +/- 11.8 IU gds(-1), respectively, were obtained through solid-state
      fermentation during the validation studies. Hydrolysis of alkali-treated rice
      straw with crude cellulases resulted in about 84% glucan to glucose, 89% xylan to
      xylose, and 91% arabinan to arabinose conversions, indicating potential for
      biomass hydrolysis by the crude cellulase consortium obtained in this study. 

PMID- 24328070
TI  - Matrix binding of ochratoxin A during roasting.
AB  - The mycotoxin ochratoxin A is degraded during coffee roasting by up to 90%.
      During this process, the two known degradation products, 14R-ochratoxin A and 14
      decarboxy-ochratoxin A are formed. However, there is still an unexplained loss of
      more than 50% ochratoxin A. Here, we describe the binding of ochratoxin A to
      coffee polysaccharides via esterification as a further thermal reaction. This
      ester formation was studied by heating ochratoxin A with methyl alpha-d
      glucopyranoside, a model compound to mimic polysaccharides. From this experiment,
      (22 -> 6') ochratoxin A-methyl-alpha-d-glucopyranoside ester was isolated and
      characterized as a reaction product, showing the general ability of ochratoxin A
      for esterification with carbohydrates at roasting temperatures. Subsequently, a
      sample preparation protocol for the detection of ochratoxin A saccharide esters
      based on an enzymatic cleavage and purification using immunoaffinity
      chromatography was developed and applied. The detection was carried out by high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using
      this method, it was possible to detect ochratoxin A polysaccharide esters formed
      during roasting of artificially contaminated coffee, confirming the results of
      the previous model experiments. Thus, the formation of ochratoxin A esters is a
      further explanation for the loss of ochratoxin A during coffee roasting. 

PMID- 24328071
TI  - Genome-wide proteomics, Chromosome-Centric Human Proteome Project (C-HPP), part
      II.

PMID- 24328072
TI  - Olefin cross-metathesis as a source of polysaccharide derivatives: cellulose
      omega-carboxyalkanoates.
AB  - Cross-metathesis has been shown for the first time to be a useful method for the
      synthesis of polysaccharide derivatives, focusing herein on preparation of
      cellulose omega-carboxyalkanoates. Commercially available cellulose esters were
      first acylated with 10-undecenoyl chloride, providing esters with olefin
      terminated side chains. Subsequent cross-metathesis of these terminal olefin
      moieties with acrylic acid was performed in solvents including acrylic acid, THF,
      and CH2Cl2. Complete conversion to discrete, soluble cross-metathesis products
      was achieved by using the Hoveyda-Grubbs second generation ruthenium catalyst and
      an excess of acrylic acid. Oligomerization during storage, caused by a free
      radical mechanism, was observed and successfully suppressed by the addition of a
      free radical scavenger (BHT). Furthermore, the cross-metathesis products
      exhibited glass transition temperatures (Tg) that were at least 50  degrees C
      higher than ambient temperature, supporting the potential for application of
      these polymers as amorphous solid dispersion matrices for enhancing drug aqueous
      solubility. 

PMID- 24328073
TI  - Combining peptide and DNA for protein assay: CRIP1 detection for breast cancer
      staging.
AB  - In this work, a novel method for a protein assay is proposed which uses the
      specific protein-binding peptide of the target protein and sequence-specific DNA
      to interact with the target as the capture and detection probe, respectively.
      Meanwhile, since the DNA sequence can be coupled with gold nanoparticles to
      amplify the signal readout, a sensitive and easily operated method for protein
      assay is developed. We have also employed a transcription factor named as
      cysteine-rich intestinal protein 1 (CRIP1), which has been identified as an ideal
      biomarker for staging of breast cancer, as the model protein for this study. With
      the proposed method, CRIP1 can be determined in a linear range from 1.25 to 10.13
      ng/mL, with a detection limit of 1.25 ng/mL. Furthermore, the proposed method can
      be directly used to assay CRIP1 in tissue samples. Owing to its desirable
      sensitivity, excellent reproducibility, and high selectivity, the proposed method
      may hold great potential in clinical practice in the future. 

PMID- 24328075
TI  - From solution to the solid state: control of niobium oxide-fluoride [NbOxFy]n-
      species.
AB  - In this study, we describe the crystallization of specific niobium oxide-fluoride
      anions (either [NbOF4](-) or [NbOF5](2-)) by increasing the fluoride
      concentration with the appropriate use of organic bases with varied corresponding
      pKa values to create suitable equilibria for the formation of each anion.
      HpyNbOF4 (I; py = pyridine) contains the [NbOF4](-) anion, while [H2(4,4'
      bpy)]NbOF5] (II; 4,4'-bpy = 4,4'-bipyridyl) contains the [NbOF5](2-) anion; their
      identity is correlated with reagent ratios. The increase of basic species (proton
      acceptors) results in an increase in the fluoride concentration and high fluoride
      containing anions. The crystallization of [NbOF4](-) in [NbO2/2F4]infinity chains
      in I was controlled with the use of weak base pyridine (pKa = 5.23), while
      isolated [NbOF5](2-) crystallized in II with strong base 4,4'-bipyridyl (pKa =
      10.5). This approach can be broadly applied to target-specific basic building
      units for fundamentally new and potentially functional solid-state materials. 

PMID- 24328074
TI  - A convergent, modular approach to functionalized 2,1-borazaronaphthalenes from 2
      aminostyrenes and potassium organotrifluoroborates.
AB  - Azaborines are an important class of compounds with applications in both
      medicinal chemistry and materials science. The first borazaronaphthalene, 2
      chloro-2,1-borazaronaphthalene, was reported in 1959; however, access to more
      highly functionalized substructures has been limited because of the harsh
      reaction conditions required to displace the chloride on boron. A convergent
      approach has been developed to synthesize disubstituted 2,1-borazaronaphthalenes
      from N-substituted 2-aminostyrenes and potassium organotrifluoroborates, where
      the potassium organotrifluoroborate is converted to the active R-BX2 species (X =
      Cl or F) in situ by addition of a fluorophile. Starting from aryl-, heteroaryl-,
      alkynyl-, alkenyl-, and alkyltrifluoroborates, a library of highly functionalized
      2,1-borazaronaphthalenes were synthesized in one step under mild, transition
      metal-free conditions. 

PMID- 24328076
TI  - Homology modeling of human muscarinic acetylcholine receptors.
AB  - We have developed homology models of the acetylcholine muscarinic receptors M1R
      M5R, based on the beta2-adrenergic receptor crystal as the template. This is the
      first report of homology modeling of all five subtypes of acetylcholine
      muscarinic receptors with binding sites optimized for ligand binding. The models
      were evaluated for their ability to discriminate between muscarinic antagonists
      and decoy compounds using virtual screening using enrichment factors, area under
      the ROC curve (AUC), and an early enrichment measure, LogAUC. The models produce
      rational binding modes of docked ligands as well as good enrichment capacity when
      tested against property-matched decoy libraries, which demonstrates their
      unbiased predictive ability. To test the relative effects of homology model
      template selection and the binding site optimization procedure, we generated and
      evaluated a naive M2R model, using the M3R crystal structure as a template. Our
      results confirm previous findings that binding site optimization using ligand(s)
      active at a particular receptor, i.e. including functional knowledge into the
      model building process, has a more pronounced effect on model quality than target
      template sequence similarity. The optimized M1R-M5R homology models are made
      available as part of the Supporting Information to allow researchers to use these
      structures, compare them to their own results, and thus advance the development
      of better modeling approaches.

PMID- 24328077
TI  - TfOH-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1-diesters with
      nitriles.
AB  - A triflic acid-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1
      diesters with nitriles was developed. This reaction was expeditious, and the
      scope of the substituents in both cyclopropanes and nitriles was broad. This
      supplies an efficient and practical method for the synthesis of 1-pyrrolines. 

PMID- 24328078
TI  - Improved protein-protein interaction assay FlimPIA by the entrapment of
      luciferase conformation.
AB  - Recently we reported a novel protein-protein interaction assay FlimPIA (firefly
      luminescent intermediate-based protein-protein interaction assay) based on the
      functional complementation of two mutant firefly luciferases (Fluc), each
      defective in its one of two half reactions. The assay detects approximation of
      two mutant Flucs, namely, a "Donor" that catalyzes ATP-driven luciferin
      adenylation to produce a luciferyl-adenylate intermediate, and an "Acceptor" that
      mainly catalyzes subsequent oxidative luminescent reaction. However, there was a
      problem in FlimPIA that the remaining adenylation activity of the Acceptor
      constituted its background signal and hampered its wider use. In this study, we
      aimed at reducing the background signal by trapping the Acceptor to the
      "oxidation" conformation, either chemically or by disulfide bonding. The results
      showed higher sensitivity and detection over the longer distance of the developed
      assay compared to conventional FlimPIA, Fluc-based protein-fragment
      complementation assay, and fluorescent protein-based FRET assay. 

PMID- 24328080
TI  - Optical and chemical characterization of aerosols emitted from coal, heavy and
      light fuel oil, and small-scale wood combustion.
AB  - Particle emissions affect radiative forcing in the atmosphere. Therefore, it is
      essential to know the physical and chemical characteristics of them. This work
      studied the chemical, physical, and optical characteristics of particle emissions
      from small-scale wood combustion, coal combustion of a heating and power plant,
      as well as heavy and light fuel oil combustion at a district heating station.
      Fine particle (PM1) emissions were the highest in wood combustion with a high
      fraction of absorbing material. The emissions were lowest from coal combustion
      mostly because of efficient cleaning techniques used at the power plant. The
      chemical composition of aerosols from coal and oil combustion included mostly
      ions and trace elements with a rather low fraction of absorbing material. The
      single scattering albedo and aerosol forcing efficiency showed that primary
      particles emitted from wood combustion and some cases of oil combustion would
      have a clear climate warming effect even over dark earth surfaces. Instead, coal
      combustion particle emissions had a cooling effect. Secondary processes in the
      atmosphere will further change the radiative properties of these emissions but
      are not considered in this study. 

PMID- 24328081
TI  - Control of molecular organization and energy level alignment by an electronically
      nanopatterned boron nitride template.
AB  - Suitable templates to steer the formation of nanostructure arrays on surfaces are
      indispensable in nanoscience. Recently, atomically thin sp(2)-bonded layers such
      as graphene or boron nitride (BN) grown on metal supports have attracted
      considerable interest due to their potential geometric corrugation guiding the
      positioning of atoms, metallic clusters or molecules. Here, we demonstrate three
      specific functions of a geometrically smooth, but electronically corrugated,
      sp(2)/metal interface, namely, BN/Cu(111), qualifying it as a unique nanoscale
      template. As functional adsorbates we employed free-base porphine (2H-P), a
      prototype tetrapyrrole compound, and tetracyanoquinodimethane (TCNQ), a well
      known electron acceptor. (i) The electronic moirons of the BN/Cu(111) interface
      trap both 2H-P and TCNQ, steering self-organized growth of arrays with extended
      molecular assemblies. (ii) We report an effective decoupling of the trapped
      molecules from the underlying metal support by the BN, which allows for a direct
      visualization of frontier orbitals by scanning tunneling microscopy (STM). (iii)
      The lateral molecular positioning in the superstructured surface determines the
      energetic level alignment; i.e., the energy of the frontier orbitals, and the
      electronic gap are tunable. 

PMID- 24328079
TI  - Neurosteroid analogues. 18. Structure-activity studies of ent-steroid
      potentiators of gamma-aminobutyric acid type A receptors and comparison of their
      activities with those of alphaxalone and allopregnanolone.
AB  - A model of the alignment of neurosteroids and ent-neurosteroids at the same
      binding site on gamma-aminobutyric acid type A (GABAA) receptors was evaluated
      for its ability to identify the structural features in ent-neurosteroids that
      enhance their activity as positive allosteric modulators of this receptor.
      Structural features that were identified included: (1) a ketone group at position
      C-16, (2) an axial 4alpha-OMe group, and (3) a C-18 methyl group. Two ent
      steroids were identified that were more potent than the anesthetic steroid
      alphaxalone in their threshold for and duration of loss of the righting reflex in
      mice. In tadpoles, loss of righting reflex for these two ent-steroids occurs with
      EC50 values similar to those found for allopregnanolone. The results indicate
      that ent-steroids have considerable potential to be developed as anesthetic
      agents and as drugs to treat brain disorders that are ameliorated by positive
      allosteric modulators of GABAA receptor function. 

PMID- 24328082
TI  - Thymol nanoemulsified by whey protein-maltodextrin conjugates: the enhanced
      emulsifying capacity and antilisterial properties in milk by propylene glycol.
AB  - The objective of this research was to enhance the capability of whey protein
      isolate-maltodextrin conjugates in nanoemulsifying thymol using propylene glycol
      to improve antilisterial properties in milk. Thymol was predissolved in PG and
      emulsified in 7% conjugate solution. Transparent dispersions with mean diameters
      of <30 nm were observed up to 1.5%w/v thymol. In skim and 2% reduced fat milk,
      Listeria monocytogenes Scott A was reduced from ~5 log CFU/mL to below the
      detection limit in 6 h by 0.1% w/v and 0.45% w/v nanoemulsified thymol,
      respectively, contrasting with gradual reductions to 1.15 and 2.26 log CFU/mL
      after 48 h by same levels of free thymol. In full fat milk, L. monocytogenes was
      gradually reduced to be undetectable after 48 h by 0.6% w/v nanoemulsified
      thymol, contrasting with the insignificant reduction by free thymol. The improved
      antilisterial activities of nanoemulsified thymol resulted from the increased
      solubility in milk and synergistic activity with propylene glycol. 

PMID- 24328083
TI  - Chromosome-8-coded proteome of Chinese Chromosome Proteome Data set (CCPD) 2.0
      with partial immunohistochemical verifications.
AB  - We upgraded the preliminary CCPD 1.0 to CCPD 2.0 using the latest deep-profiling
      proteome (CCPD 2013) of three hepatocellular carcinoma (HCC) cell lines, namely,
      Hep3B, MHCC97H, and HCCLM3 (ProteomeXchange identifiers: PXD000529, PXD000533,
      and PXD000535). CCPD 2.0 totally covered 63.6% (438/689) of Chr. 8-coded proteins
      and 62.6% (439/701) of Chr. 8-coded protein-coding genes. Interestingly, we found
      that the missing proteins exhibited a tendency to form a cluster region in
      chromosomes, such as two beta-defensins clusters in Chr. 8, caused perhaps by
      their inflammation-related features. For the 41 Chr. 8-coded proteins being
      weakly or barely identified previously, we have performed an immunohistochemical
      (IHC) verification in 30 pairs of carcinoma/para-carcinoma HCC and 20
      noncancerous liver tissues and confirmed their expressional evidence and
      occurrence proportions in tissue samples. We also verified 13 Chr. 8-coded HCC
      tumorigenesis-associated depleting or deficient proteins reported in CCPD 1.0
      using IHC and screened 16 positive and 24 negative HCC metastatic potential
      correlated proteins from large-scale label-free proteome quantitation data of
      CCPD 2013. Our results suggest that the selection of proper samples and the
      methodology to look for targeted missing proteins should be carefully considered
      in further verifications for the remaining Chr. 8-coded proteins. 

PMID- 24328085
TI  - Two-photon fluorescent probes for metal ions in live tissues.
AB  - Two-photon microscopy (TPM) is a new imaging tool that can detect biological
      targets deep inside a live tissue. To faciltate the use of TPM in biomedical
      research, a variety of two-photon (TP) probes for specific applications are
      needed. In this Forum Article, we describe the design strategy, photophysical
      properties, and biological imaging applications of a selection of our recent
      studies in the development of TP probes for metal ions. Small-molecule TP turn-on
      probes, organelle-targeted probes, and multicolor emissive probes for dual-color
      imaging are briefly reviewed. 

PMID- 24328084
TI  - Metabolomic analysis of the effects of chronic arsenic exposure in a mouse model
      of diet-induced Fatty liver disease.
AB  - Arsenic is a widely distributed environmental component that is associated with a
      variety of cancer and non-cancer adverse health effects. Additional lifestyle
      factors, such as diet, contribute to the manifestation of disease. Recently,
      arsenic was found to increase inflammation and liver injury in a dietary model of
      fatty liver disease. The purpose of the present study was to investigate
      potential mechanisms of this diet-environment interaction via a high-throughput
      metabolomics approach. GC*GC-TOF MS was used to identify metabolites that were
      significantly increased or decreased in the livers of mice fed a Western diet (a
      diet high in fat and cholesterol) and co-exposed to arsenic-contaminated drinking
      water. The results showed that there are distinct hepatic metabolomic profiles
      associated with eating a high fat diet, drinking arsenic-contaminated water, and
      the combination of the two. Among the metabolites that were decreased when
      arsenic exposure was combined with a high fat diet were short-chain and medium
      chain fatty acid metabolites and the anti-inflammatory amino acid, glycine. These
      results are consistent with the observed increase in inflammation and cell death
      in the livers of these mice and point to potentially novel mechanisms by which
      these metabolic pathways could be altered by arsenic in the context of diet
      induced fatty liver disease. 

PMID- 24328086
TI  - Modulating beta-lactoglobulin nanofibril self-assembly at pH 2 using glycerol and
      sorbitol.
AB  - beta-Lactoglobulin (beta-lg) forms fibrils when heated at 80  degrees C, pH 2,
      and low ionic strength (<0.015 mM). When formed at protein concentrations <3%,
      these fibrils are made up of peptides produced from the acid hydrolysis of the
      beta-lg monomer. The present study investigated the effects of the polyhydroxy
      alcohols (polyols) glycerol and sorbitol (0-50% w/v) on beta-lg self-assembly at
      pH 2. Glycerol and sorbitol stabilize native protein structure and modulate
      protein functionality by preferential exclusion. In our study, both polyols
      decreased the rate of beta-lg self-assembly but had no effect on the morphology
      of fibrils. The mechanism of these effects was studied using circular dichroism
      spectroscopy and SDS-PAGE. Sorbitol inhibited self-assembly by stabilizing beta
      lg against unfolding and hydrolysis, resulting in fewer fibrillogenic species,
      whereas glycerol inhibited nucleation without inhibiting hydrolysis. Both polyols
      increased the viscosity of the solutions, but viscosity appeared to have little
      effect on fibril assembly, and we believe that self-assembly was not diffusion
      limited under these conditions. This is in agreement with previous reports for
      other proteins assembling under different conditions. The phenomenon of peptide
      self-assembly can be decoupled from protein hydrolysis using glycerol. 

PMID- 24328087
TI  - Detection and identification of Cu2+ and Hg2+ based on the cross-reactive
      fluorescence responses of a dansyl-functionalized film in different solvents.
AB  - A dansyl-functionalized fluorescent film sensor was specially designed and
      prepared by assembling dansyl on a glass plate surface via a long flexible spacer
      containing oligo(oxyethylene) and amine units. The chemical attachment of dansyl
      moieties on the surface was verified by contact angle, XPS, and fluorescence
      measurements. Solvent effect examination revealed that the polarity-sensitivity
      was retained for the surface-confined dansyl moieties. Fluorescence quenching
      studies in water declared that the dansyl-functionalized SAM possesses a higher
      sensitivity towards Hg(2+) and Cu(2+) than the other tested divalent metal ions
      including Zn(2+), Cd(2+), Co(2+), and Pb(2+). Further measurements of the
      fluorescence responses of the film towards Cu(2+) and Hg(2+) in three solvents
      including water, acetonitrile, and THF evidenced that the present film exhibits
      cross-reactive responses to these two metal ions. The combined signals from the
      three solvents provide a recognition pattern for both metal ions at a certain
      concentration and realize the identification between Hg(2+) and Cu(2+). Moreover,
      using principle component analysis, this method can be extended to identify metal
      ions that are hard to detect by the film sensor in water such as Co(2+) and
      Ni(2+). 

PMID- 24328088
TI  - Uptake of gas phase nitrous acid onto boundary layer soil surfaces.
AB  - Nitrous acid (HONO) is an important OH radical source that is formed on both
      ground and aerosol surfaces in the well-mixed boundary layer. Large uncertainties
      remain in quantifying HONO sinks and determining the mechanism of HONO uptake
      onto surfaces. We report here the first laboratory determination of HONO uptake
      coefficients onto actual soil under atmospheric conditions using a coated-wall
      flow tube coupled to a highly sensitive chemical ionization mass spectrometer
      (CIMS). Uptake coefficients for HONO decrease with increasing RH from (2.5 +/-
      0.4) * 10(-4) at 0% RH to (1.1 +/- 0.4) * 10(-5) at 80% RH. A kinetics model of
      competitive adsorption of HONO and water onto the particle surfaces fits the
      dependence of the HONO uptake coefficients on the initial HONO concentration and
      relative humidity. However, a multiphase resistor model based on the physical and
      chemical processes affecting HONO uptake is more flexible as it accounts for the
      pH dependence of HONO uptake and bulk diffusion in the soil matrix. Fourier
      transform infrared (FTIR) spectrometry and cavity-enhanced absorption
      spectroscopy (CEAS) studies indicate that NO and N2O (16% and 13% yield,
      respectively) rather than NO2 are the predominant gas phase products, while NO2(
      ) and NO3(-) were detected on the surface post-exposure. Results are compared to
      uptake coefficients inferred from models and field measurements, and the
      atmospheric implications are discussed. 

PMID- 24328090
TI  - Gold-catalyzed tandem [3,3]-propargyl ester rearrangement leading to (E)-1H-inden
      1-ones.
AB  - An efficient method for the synthesis of (E)-1H-inden-1-ones using gold-catalyzed
      tandem [3,3]-propargyl ester rearrangement followed by Michael addition under
      mild reaction conditions has been developed. The resulting products are important
      frameworks found in numerous natural products and pharmaceutically active
      compounds, as well as being valuable intermediates in organic synthesis. 

PMID- 24328089
TI  - Base pair opening in a deoxynucleotide duplex containing a cis-syn thymine
      cyclobutane dimer lesion.
AB  - The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin
      cancer. We compared the stability of individual base pairs in thymine dimer
      containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic
      measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the
      thymine dimer lesion is locally and moderately destabilizing within an overall B
      form duplex conformation. We measured the rates of exchange of individual imino
      protons by NMR using magnetization transfer from water and determined the
      equilibrium constant for the opening of each base pair K(op). In the normal
      duplex K(op) decreases from the frayed ends of the duplex toward the center, such
      that the central TA pair is the most stable with a K(op) of 8 * 10-7. In
      contrast, base pair opening at the 5'T of the thymine dimer is facile. The 5'T of
      the dimer has the largest equilibrium constant (K(op) = 3 * 10-4) in its duplex,
      considerably larger than even the frayed penultimate base pairs. Notably, base
      pairing by the 3'T of the dimer is much more stable than by the 5'T, indicating
      that the predominant opening mechanism for the thymine dimer lesion is not likely
      to be flipping out into solution as a single unit. The dimer asymmetrically
      affects the stability of the duplex in its vicinity, destabilizing base pairing
      on its 5' side more than on the 3' side. The striking differences in base pair
      opening between parent and dimer duplexes occur independently of the duplex
      single strand melting transitions.

PMID- 24328091
TI  - Predicting GPCR promiscuity using binding site features.
AB  - G protein-coupled receptors (GPCRs) represent a large family of signaling
      proteins that includes many therapeutic targets. GPCR ligands include odorants,
      tastants, and neurotransmitters and vary in size and properties. Dramatic
      chemical diversity may occur even among ligands of the same receptor. Our goal is
      to unravel the structural and chemical features that determine GPCRs' promiscuity
      toward their ligands. We perform statistical analysis using more than 30
      descriptors related to the sequence, physicochemical, structural, and energetic
      properties of the GPCR binding sites-we find that the chemical variability of
      antagonists significantly correlates with the binding site hydrophobicity and
      anticorrelates with the number of hydrogen bond donors in the binding site. The
      number of disulfide bridges in the extracellular region of a receptor
      anticorrelates with the range of molecular weights of its antagonists,
      highlighting the role of the entrance pathway in determining the size selectivity
      for GPCR antagonists. The predictive capability of the model is successfully
      validated using a separate set of GPCRs, using either X-ray structures or
      homology models. 

PMID- 24328092
TI  - Glycosylation characterization of human and porcine fibrinogen proteins by lectin
      binding biophotonic microarray imaging.
AB  - Lectin binding has been studied using the particle plasmon light-scattering
      properties of gold nanoparticles printed into an array format. Performance of the
      kinetic assay is evaluated from a detailed analysis of the binding of
      concanavalin A (ConA) and wheat germ agglutinin (WGA) to their target
      monosaccharides indicating affinity constants in the order of KD ~10 nM for the
      lectin-monosaccharide interaction. The detection limits for the lectins following
      a 200 s injection time were determined as 10 ng/mL or 0.23 nM and 100 ng/mL or
      0.93 nM, respectively. Subsequently, a nine-lectin screen was performed on the
      porcine and human fibrinogen glycoproteins. The observed spectra of lectin
      protein specific binding rates result in characteristic patterns that evidently
      correlate with the structure of the glycans and allow one to distinguish between
      glycosylation of the porcine and human fibrinogens. The array technology has the
      potential to perform a multilectin screen of large numbers of proteins providing
      information on protein glycosylation and their microheterogeneity. 

PMID- 24328093
TI  - Radical-scavenging compounds from olive tree (Olea europaea L.) wood.
AB  - The purpose of this study was to complete knowledge on the chemical composition
      and radical-scavenging activity of olive tree wood. Two new monoterpene
      glycosides, (-)-oleuropeic acid 6'-O-alpha-D-glucopyranosyl ester (6a) and (-)
      perillic acid 1'-O-beta-D-primeverosyl ester (8), together with the known
      compounds (-)-oleuropeic acid (1), (-)-olivil (2), the aldehydic form of
      oleuropein aglycone (3), (+)-1-hydroxypinoresinol 1-O-beta-D-glucopyranoside (4),
      (-)-oleuropeic acid 1'-O-beta-D-glucopyranosyl ester (5), (-)-oleuropeic acid 6'
      O-beta-D-glucopyranosyl ester (6b), and (-)-olivil 4-O-beta-D-glucopyranoside (7)
      were isolated from an ethyl acetate extract. The radical scavengers found (2-4
      and 7) were detected and isolated with the help of the online HPLC-DAD-DPPH/ABTS
      technique. Compounds 2-4 and 7 displayed a higher antioxidative effect against
      the free radical DPPH than the reference BHT and lower than hydroxytyrosol,
      whereas compounds 1, 5, 6a, 6b, and 8 showed no activity.

PMID- 24328094
TI  - Effect of urea concentration on aggregation of amyloidogenic hexapeptides
      (NFGAIL).
AB  - We have performed large-scale all-atom molecular dynamics (MD) simulations to
      study the aggregation behavior of four NFGAIL hexapeptides in the aqueous urea
      solution, with a urea concentration ranging from 0 to 5 M. We find that urea in
      general suppresses the peptide aggregation, but suppression slows down in the
      intermediation concentration regime around 3 M. Two competing mechanisms of urea
      are determined: urea molecules accumulated near the first solvation shell (FSS)
      tend to unfold the hexapeptide, which favors aggregation; on the other hand, the
      tight hydrogen bonds formed between urea and peptide mainchains hinder the
      association of peptides which disfavors the formation of the beta-sheet.
      Furthermore, the different nonlinear urea concentration dependences of the urea
      peptide and peptide-peptide hydrogen bonds lead to a nonmonotonic behavior, with
      a weak enhancement in the peptide aggregation around 3 M. 

PMID- 24328095
TI  - Fast serial analysis of active cholesterol at the plasma membrane in single
      cells.
AB  - Previously, our group has utilized the luminol electrochemiluminescence to
      analyze the active cholesterol at the plasma membrane in single cells by the
      exposure of one cell to a photomultiplier tube (PMT) through a pinhole. In this
      paper, fast analysis of active cholesterol at the plasma membrane in single cells
      was achieved by a multimicroelectrode array without the pinhole. Single cells
      were directly located on the microelectrodes using cell-sized microwell traps. A
      cycle of voltage was applied on the microelectrodes sequentially to induce a peak
      of luminescence from each microelectrode for the serial measurement of active
      membrane cholesterol. A minimal time of 1.60 s was determined for the analysis of
      one cell. The simulation and the experimental data exhibited a semisteady-state
      distribution of hydrogen peroxide on the microelectrode after the reaction of
      cholesterol oxidase with the membrane cholesterol, which supported the relative
      accuracy of the serial analysis. An eight-microelectrode array was demonstrated
      to analyze eight single cells in 22 s serially, including the channel switching
      time. The results from 64 single cells either activated by low ion strength
      buffer or the inhibition of intracellular acyl-coA/cholesterol acyltransferase
      (ACAT) revealed that most of the cells analyzed had the similar active membrane
      cholesterol, while few cells had more active cholesterol resulting in the
      cellular heterogeneity. The fast single-cell analysis platform developed will be
      potentially useful for the analysis of more molecules in single cells using
      proper oxidases. 

PMID- 24328096
TI  - Integral membrane protein fragment recombination after transfer from
      nanolipoprotein particles to bicelles.
AB  - A new method for the measurement of membrane protein oligomer association is
      described. Two engineered fragments of bacteriorhodopsin, which are known to
      spontaneously associate in bicelles, were expressed in nanolipoprotein particles
      (NLPs or nanodiscs) using an Escherichia coli S30 cell-free synthesis system.
      When separately prepared NLPs containing the fragments were mixed, fragment
      association did not occur, indicating that the apolipoprotein edge blocks
      transfer between NLPs. However, when bicelles were added to this mixture,
      fragment association was detected by disulfide cross-linking. The rate of cross
      linking was consistent with previously published equilibrium and kinetic
      parameters. Characterization of the NLP/bicelle mixture by dynamic light
      scattering and fluorescence spectroscopy indicates that the NLP bilayer transfers
      to bicelles in a simple reversal of the synthesis of NLPs from bicelles. These
      experiments validate using cell-free synthesis of membrane proteins in NLPs,
      followed by treatment with bicelles, as a method for measuring oligomerization of
      integral membrane protein subunits in a bilayer-like environment. 

PMID- 24328097
TI  - SILAC peptide ratio calculator: a tool for SILAC quantitation of peptides and
      post-translational modifications.
AB  - This paper describes an algorithm to assist in relative quantitation of peptide
      post-translational modifications using stable isotope labeling by amino acids in
      cell culture (SILAC). The described algorithm first determines the normalization
      factor and then calculates SILAC ratios for a list of target peptide masses using
      precursor ion abundances. Four yeast histone mutants were used to demonstrate the
      effectiveness of this approach for quantitation of peptide post-translational
      modifications changes. The details of the algorithm's approach for normalization
      and peptide ratio calculation are described. The examples demonstrate the
      robustness of the approach as well as its utility to rapidly determine changes in
      peptide post-translational modifications within a protein. 

PMID- 24328098
TI  - In vitro membrane protein synthesis inside cell-sized vesicles reveals the
      dependence of membrane protein integration on vesicle volume.
AB  - Giant unilamellar vesicles (GUVs) are vesicles>1 MUm in diameter that provide an
      environment in which the effect of a confined reaction volume on intravesicular
      reactions can be investigated. By synthesizing EmrE, a multidrug transporter from
      Escherichia coli, as a model membrane protein using a reconstituted in vitro
      transcription-translation system inside GUVs, we investigated the effect of a
      confined volume on the synthesis and membrane integration of EmrE. Flow cytometry
      was used to analyze multiple properties of the vesicles and to quantify EmrE
      synthesis inside GUVs composed of only 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine. We found that EmrE was synthesized and integrated into the GUV
      membrane in its active form. We also found that the ratio of membrane-integrated
      EmrE to total synthesized EmrE increased with decreasing vesicle volume; this
      finding is explained by the effect of an increased surface-area-to-volume ratio
      in smaller vesicles. In vitro membrane synthesis inside GUVs is a useful approach
      to study quantitatively the properties of membrane proteins and their interaction
      with the membrane under cell-mimicking environments.

PMID- 24328099
TI  - Enhanced cell affinity of chitosan membranes mediated by superficial cross
      linking: a straightforward method attainable by standard laboratory procedures.
AB  - It is well accepted that the surface modification of biomaterials can improve
      their biocompatibility. In this context, techniques like ion etching, plasma
      mediated chemical functionalization, electrospinning, and contact microprinting
      have successfully been employed to promote the cell adhesion and proliferation of
      chitosan (CH) substrates. However, they prove to be time-consuming, highly
      dependent on environmental conditions, and/or limited to the use of expensive
      materials and sophisticated instruments not accessible to standard laboratories,
      hindering to a high extent their straightforward application. Filling this gap,
      this paper proposes the superficial cross-linking of CH as a much simpler and
      accessible means to modify its superficial properties in order to enhance its
      cellular affinity. CH membranes were prepared by solvent casting followed by a
      cross-linking step mediated by the chemical vapor deposition (CVD) of
      glutaraldehyde (GA). The membranes were characterized against non- and solution
      cross-linked membranes in terms of their mechanical/surface properties and
      biological performance. Among others, the CVD membranes proved (i) to be more
      mechanically stable against cell culture and sterilization than membranes cross
      linked in solution and (ii) to prompt the adherence and sustained proliferation
      of healthy cells to levels even superior to commercial tissue culture plates
      (TCPs). Accordingly, the CVD cross-linking approach was demonstrated to be a
      simple and cost-effective alternative to the aforementioned conventional methods.
      Interestingly, this concept can also be applied to other biomaterials as long as
      GA (or other volatile components alike) can be employed as a cross-linker, making
      possible the cross-linking reaction at mild experimental conditions, neither
      requiring sophisticated lab implements nor using any potentially harmful
      procedure. 

PMID- 24328100
TI  - Analysis of the hydration water around bovine serum albumin using terahertz
      coherent synchrotron radiation.
AB  - Terahertz spectroscopy was used to study the absorption of bovine serum albumin
      (BSA) in water. The Diamond Light Source operating in a low alpha mode generated
      coherent synchrotron radiation that covered a useable spectral bandwidth of 0.3
      3.3 THz (10-110 cm(-1)). As the BSA concentration was raised, there was a
      nonlinear change in absorption inconsistent with Beer's law. At low BSA
      concentrations (0-1 mM), the absorption remained constant or rose slightly. Above
      a concentration of 1 mM BSA, a steady decrease in absorption was observed, which
      was followed by a plateau that started at 2.5 mM. Using a overlapping hydration
      layer model, the hydration layer was estimated to extend 15 A from the protein.
      Calculation of the corrected absorption coefficient (alphacorr) for the water
      around BSA by subtracting the excluded volume of the protein provides an
      alternative approach to studying the hydration layer that provides evidence for
      complexity in the population of water around BSA. 

PMID- 24328101
TI  - Construction of an M3L2A6 cage with small windows from a flexible tripodal ligand
      and Cu(hfac)3.
AB  - An M3L2A6 cage has been prepared with small windows from a tripodal ligand, L,
      and Cu(hfac)2. Cold spray ionization mass spectrometry of a mixture of L and
      Cu(hfac)2 revealed the formation of a Cu3L2hfac6 cage in solution. X-ray
      crystallography showed that the Cu3L2hfac6 cage included neutral molecules such
      as THF and CHCl3. Furthermore, the six hfac anions have been shown to play an
      important role in holding neutral guest molecules securely in place. 

PMID- 24328102
TI  - Ammonium addition (and aerosol pH) has a dramatic impact on the volatility and
      yield of glyoxal secondary organic aerosol.
AB  - Glyoxal is an important precursor to secondary organic aerosol (SOA) formed
      through aqueous chemistry in clouds, fogs, and wet aerosols, yet the gas-particle
      partitioning of the resulting mixture is not well understood. This work
      characterizes the volatility behavior of the glyoxal precursor/product mix formed
      after aqueous hydroxyl radical oxidation and droplet evaporation under cloud
      relevant conditions for 10 min, thus aiding the prediction of SOA via this
      pathway (SOACld). This work uses kinetic modeling for droplet composition,
      droplet evaporation experiments and temperature-programmed desorption aerosol
      chemical ionization mass spectrometer analysis of gas-particle partitioning. An
      effective vapor pressure (p'L,eff) of ~10(-7) atm and an enthalpy of vaporization
      (DeltaHvap,eff) of ~70 kJ/mol were estimated for this mixture. These estimates
      are similar to those of oxalic acid, which is a major product. Addition of
      ammonium until the pH reached 7 (with ammonium hydroxide) reduced the p'L,eff to
      <10(-9) atm and increased the DeltaHvap,eff to >80 kJ/mol, at least in part via
      the formation of ammonium oxalate. pH 7 samples behaved like ammonium oxalate,
      which has a vapor pressure of ~10(-11) atm. We conclude that ammonium addition
      has a large effect on the gas-particle partitioning of the mixture, substantially
      enhancing the yield of SOACld from glyoxal. 

PMID- 24328103
TI  - Discovery of a non-estrogenic irreversible inhibitor of 17beta-hydroxysteroid
      dehydrogenase type 1 from 3-substituted-16beta-(m-carbamoylbenzyl)-estradiol
      derivatives.
AB  - 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is thought to play a
      pivotal role in the progression of estrogen-sensitive breast cancer by
      transforming estrone (E1) into estradiol (E2). We designed three successive
      series of E2-derivatives at position C3 of the potent inhibitor 16beta-(m
      carbamoylbenzyl)-E2 to remove its unwanted estrogenic activity. We report the
      chemical synthesis and characterization of 20 new E2-derivatives, their
      evaluation as 17beta-HSD1 inhibitors, and their proliferative (estrogenic)
      activity on estrogen-sensitive cells. The structure-activity relationship study
      provided a new potent and steroidal nonestrogenic inhibitor of 17beta-HSD1 named
      3-{[(16beta,17beta)-3-(2-bromoethyl)-17-hydroxyestra-1(10),2,4-trien-16
      yl]methyl}benzamide (23b). In fact, this compound inhibited the transformation of
      E1 into E2 by 17beta-HSD1 in T-47D cells (IC50 = 83 nM), did not inhibit 17beta
      HSD2, 17beta-HSD7, 17beta-HSD12, and CYP3A4, and did not stimulate the
      proliferation of estrogen-sensitive MCF-7 cells. We also discussed the results of
      kinetic and molecular modeling (docking) experiments, suggesting that compound
      23b is a competitive and irreversible inhibitor of 17beta-HSD1. 

PMID- 24328104
TI  - Photophysical and dynamical properties of doubly linked Cy3-DNA constructs.
AB  - Photophysical measurements are reported for Cy3-DNA constructs in which both Cy3
      nitrogen atoms are attached to the DNA backbone by short linkers. While this
      linking was thought to rigidify the orientation of the dye and hinder cis
      isomerization, the relatively low fluorescence quantum yield and the presence of
      a short component in the time-resolved fluorescence decay of the dye indicated
      that cis-isomerization remained possible. Fluorescence correlation spectroscopy
      and transient absorption experiments showed that photoisomerization occurred with
      high efficiency. Molecular dynamics simulations of the trans dye system indicated
      the presence of stacked and unstacked states, and free energy simulations showed
      that the barriers for stacking/unstacking were low. In addition, simulations
      showed that the ground cis state was feasible without DNA distortions. Based on
      these observations, a model is put forward in which the doubly linked dye can
      photoisomerize in the unstacked state. 

PMID- 24328105
TI  - Crystal structure of Korean pine (Pinus koraiensis) 7S seed storage protein with
      copper ligands.
AB  - The prevalence of food allergy has increased in recent years, and Korean pine
      vicilin is a potential food allergen. We have previously reported the
      crystallization of Korean pine vicilin purified from raw pine nut. Here we report
      the isolation of vicilin mRNA and the crystal structure of Korean pine vicilin at
      2.40 A resolution. The overall structure of pine nut vicilin is similar to the
      structures of other 7S seed storage proteins and consists of an N-terminal domain
      and a C-terminal domain. Each assumes a cupin fold, and they are symmetrically
      related about a pseudodyad axis. Three vicilin molecules form a doughnut-shaped
      trimer through head-to-tail association. Structure characterization of Korean
      pine nut vicilin unexpectedly showed that, in its native trimeric state, the
      vicilin has three copper ligands. Sequence alignments suggested that the copper
      coordinating residues were conserved in winter squash, sesame, tomato, and
      several tree nuts, while they were not conserved in a number of legumes,
      including peanut and soybean. Additional studies are needed to assess whether the
      copper-coordinating property of vicilins has a biological function in the
      relevant plants. The nutritional value of this copper-coordinating protein in
      tree nuts and other edible seeds may be worth further investigations. 

PMID- 24328106
TI  - Model studies directed toward the alkaloid mersicarpine utilizing a Rh(II)
      catalyzed insertion/cycloaddition sequence.
AB  - Model studies dealing with the rhodium(II)-catalyzed carbenoid
      insertion/cyclization/cycloaddition cascade of several alpha-diazo
      dihydroindolinones have been carried out as an approach to the alkaloid
      mersicarpine. The cascade reaction of alpha-diazo dihydroindolinone 21 proceeded
      in high yield with excellent diastereoselectivity to give cycloadduct 22, which
      possesses the required stereochemistry of the two adjacent quaternary carbon
      centers present in mersicarpine. The overall reaction enabled the rapid
      assemblage of a polycyclic ring system that contains three new stereocenters and
      three continuous quaternary carbons in a single operation in high yield with
      excellent diastereoselectivity. The 3-indolinone derivative 36 was eventually
      formed from cycloadduct 22 by an acid-induced hydrolysis of 22 to give 23, which
      was subsequently converted in several steps to 36. The synthesis of this compound
      constitutes a successful construction of the tricyclic core of mersicarpine.
      Reduction of the nitrile group of 36 followed by a subsequent reductive
      cyclization/ring-opening aromatization cascade, as was found to occur with the
      related compound 29, will be employed for an eventual synthesis of
      demethylmersicarpine. 

PMID- 24328108
TI  - Isolated RING2 domain of parkin is sufficient for E2-dependent E3 ligase
      activity.
AB  - The E3 ubiquitin ligase activity of the parkin protein is implicated in playing a
      protective role against neurodegenerative disorders including Parkinson's,
      Huntington's, and Alzheimer's diseases. Parkin has four zinc-containing domains:
      RING0, RING1, IBR (in-between ring), and RING2. Mutational analysis of full
      length parkin suggests that the C-terminal RING2 domain contains the catalytic
      core. Here, a catalytically competent recombinant RING2 containing an N-terminal
      GB1 solubility peptide is described. In cell-free in vitro ubiqitination
      reactions, the RING2 construct catalyzes the transfer of ubiquitin from the E2
      enzyme UbcH7 to the attached GB1 tag. This intramolecular autoubiquitination
      reaction indicates that (a) ubiquitination by RING2 can occur in the absence of
      other parkin domains and (b) UbcH7 can interact directly with RING2 to transfer
      its bound ubiquitin. Mass spectrometry identified sites of mono- and diubiquitin
      attachment to two surface-exposed lysine residues (Lys24 and Lys39) on the GB1
      peptide. The sites of diubiquitination involved Lys11 and Lys48 linkages, which
      have been identified as general signals for proteasome degradation. Cleaving the
      linker between the GB1 tag and RING2 resulted in loss of ubiquitination activity,
      indicating that the substrate must be tethered to RING2 for proper presentation
      to the active site. Atomic absorption spectrometry and selective mutation of zinc
      ligands indicated that only one of the two zinc binding sites on RING2, the N
      terminal site, needs to be occupied by zinc for expression of ubiquitination
      activity. This is consistent with the hypothesis that the second, C-terminal,
      zinc binding site on RING2 has a regulatory rather than a catalytic function. 

PMID- 24328107
TI  - Site-specific characterization of (D)-amino acid containing peptide epimers by
      ion mobility spectrometry.
AB  - Traditionally, the d-amino acid containing peptide (DAACP) candidate can be
      discovered by observing the differences of biological activity and
      chromatographic retention time between the synthetic peptides and naturally
      occurring peptides. However, it is difficult to determine the exact position of d
      amino acid in the DAACP candidates. Herein, we developed a novel site-specific
      strategy to rapidly and precisely localize d-amino acids in peptides by ion
      mobility spectrometry (IMS) analysis of mass spectrometry (MS)-generated epimeric
      fragment ions. Briefly, the d/l-peptide epimers were separated by online reversed
      phase liquid chromatography and fragmented by collision-induced dissociation
      (CID), followed by IMS analysis. The epimeric fragment ions resulting from d/l
      peptide epimers exhibit conformational differences, thus showing different
      mobilities in IMS. The arrival time shift between the epimeric fragment ions was
      used as criteria to localize the d-amino acid substitution. The utility of this
      strategy was demonstrated by analysis of peptide epimers with different molecular
      sizes, [d-Trp]-melanocyte-stimulating hormone, [d-Ala]-deltorphin, [d-Phe]
      achatin-I, and their counterparts that contain all-l amino acids. Furthermore,
      the crustacean hyperglycemia hormones (CHHs, 8.5 kDa) were isolated from the
      American lobster Homarus americanus and identified by integration of MS-based
      bottom-up and top-down sequencing approaches. The IMS data acquired using our
      novel site-specific strategy localized the site of isomerization of l- to d-Phe
      at the third residue of the CHHs from the N-terminus. Collectively, this study
      demonstrates a new method for discovery of DAACPs using IMS technique with the
      ability to localize d-amino acid residues. 

PMID- 24328109
TI  - Phosphoproteome analysis of formalin-fixed and paraffin-embedded tissue sections
      mounted on microscope slides.
AB  - Formalin-fixed and paraffin-embedded (FFPE) sections mounted on microscope slides
      are one of the largest available resources for retrospective research on various
      diseases, but quantitative phosphoproteome analysis of FFPE sections has never
      been achieved because of the extreme difficulty of procuring sufficient
      phosphopeptides from the limited amounts of proteins on the slides. Here, we
      present the first protocol for quantitative phosphoproteome analysis of FFPE
      sections by utilizing phase-transfer surfactant-aided extraction/tryptic
      digestion of FFPE proteins followed by high-recovery phosphopeptide enrichment
      via lactic acid-modified titania chromatography. We established that FFPE
      sections retain a similar phosphoproteome to fresh tissue specimens during
      storage for at least 9 months, confirming the utility of our method for
      evaluating phosphorylation profiles in various diseases. We also verified that
      chemical labeling based on reductive dimethylation of amino groups was feasible
      for quantitative phosphoproteome analysis of FFPE samples on slides. Furthermore,
      we improved the LC-MS sensitivity by miniaturizing nanoLC columns to 25 MUm inner
      diameter. With this system, we could identify 1090 phosphopeptides from a single
      FFPE section obtained from a microscope slide, containing 25.2 +/- 5.4 MUg of
      proteins. This protocol should be useful for large-scale phosphoproteome analysis
      of archival FFPE slides, especially scarce samples from patients with rare
      diseases. 

PMID- 24328110
TI  - Anion-tunable configuration isomerism and magnetic coupling in a tetranuclear
      discrete, one-dimensional (1D) chiral chain and 1D-decker copper(II) complexes of
      a carbohydrazine derivative.
AB  - The reactions of ligand N'-[(pyridin-2-yl)methylene]pyrazine-2-carbohydrazide
      (ppcd) with different copper salts (1, acetate; 2, perchlorate; 3, sulfate) in
      MeOH could afford one acetate-bridge tetranuclear discrete
      [Cu2(ppcd)(ac)2(H2O)(OH)]2.H2O (1), one-dimensional (1D) chiral chain
      [Cu(ppcd)]ClO4 (2), and a 1D-decker complex of a trinuclear copper(II) subunit,
      Cu3(ppcd)2(H2O)4(SO4)2 (3). Single-crystal X-ray analysis revealed that
      conformation isomerism of the ppcd ligand was associated with the configuration
      of -N-N- (trans or cis) and could induce the versatile coordination mode in the
      presence of different anions. The 1D chiral chain was interestingly obtained from
      the achiral rigid ligand in complex 2. Magnetic studies indicated that the
      magnitude of the antiferromagnetic coupling can be tuned because of the
      configuration isomerism [compound 1 is practically diamagnetic at room
      temperature (J ~ -1000 cm(-1)), with a strong antiferromagnetic one (J = -255.4
      cm(-1)) for 2 in the 1D uniform chain and an antiferromagnetic one (J = -123.6
      cm(-1)) for 3 within the trinuclear copper subunit]. 

PMID- 24328111
TI  - Conformational equilibria in butane-1,4-diol: a benchmark of a prototypical
      system with strong intramolecular H-bonds.
AB  - Explicitly correlated CCSD(T) valence basis limit relative energies were obtained
      for the 65 conformers of butane-1,4-diol, a prototypical system with a strong
      internal hydrogen bond. The performance of a variety of ab initio and DFT methods
      (with and without empirical dispersion corrections) was assessed in detail.
      Consideration of all pairwise conformer energies provides a performance gauge for
      both H-bonds and van der Waals interactions, aside from internal strain of angles
      and bonds. In the post-HF realm, it was found that SCS(MI)CCSD-F12/cc-pVDZ-F12
      can be a cost-effective alternative to CCSD(T)/CBS, almost without any loss in
      accuracy. In the DFT arena, the double-hybrid DSD-PBEP86-D3BJ surpasses the
      accuracy of all other methods (except for SCS(MI)CCSD, but at a small fraction of
      its cost). Several hybrid functionals provide an acceptable accuracy with the
      def2-QZVP basis set, especially BMK, M06, LC-omegaPBE-D3, and TPSS0-D3. With the
      more modest 6-311+G(d,p) basis set, the H-bonds are far from basis set
      completeness and, due to error compensation, the inclusion of a dispersion
      correction is generally counterproductive. Some functionals that represent
      "Pauling points" at this level are LC-omegaPBE, TPSS0, B1B95, BMK, TPSSh, PBE0,
      TPSS, and omegaB97X. 

PMID- 24328112
TI  - High-global warming potential F-gas emissions in California: comparison of
      ambient-based versus inventory-based emission estimates, and implications of
      refined estimates.
AB  - To provide information for greenhouse gas reduction policies, the California Air
      Resources Board (CARB) inventories annual emissions of high-global-warming
      potential (GWP) fluorinated gases, the fastest growing sector of greenhouse gas
      (GHG) emissions globally. Baseline 2008 F-gas emissions estimates for selected
      chlorofluorocarbons (CFC-12), hydrochlorofluorocarbons (HCFC-22), and
      hydrofluorocarbons (HFC-134a) made with an inventory-based methodology were
      compared to emissions estimates made by ambient-based measurements. Significant
      discrepancies were found, with the inventory-based emissions methodology
      resulting in a systematic 42% under-estimation of CFC-12 emissions from older
      refrigeration equipment and older vehicles, and a systematic 114% overestimation
      of emissions for HFC-134a, a refrigerant substitute for phased-out CFCs. Initial,
      inventory-based estimates for all F-gas emissions had assumed that equipment is
      no longer in service once it reaches its average lifetime of use. Revised
      emission estimates using improved models for equipment age at end-of-life,
      inventories, and leak rates specific to California resulted in F-gas emissions
      estimates in closer agreement to ambient-based measurements. The discrepancies
      between inventory-based estimates and ambient-based measurements were reduced
      from -42% to -6% for CFC-12, and from +114% to +9% for HFC-134a. 

PMID- 24328113
TI  - Synthesis and evaluation of analogues of N-phthaloyl-l-tryptophan (RG108) as
      inhibitors of DNA methyltransferase 1.
AB  - DNA methyltransferases (DNMT) are promising drug targets in cancer provided that
      new, more specific, and chemically stable inhibitors are discovered. Among the
      non-nucleoside DNMT inhibitors, N-phthaloyl-l-tryptophan 1 (RG108) was first
      identified as inhibitor of DNMT1. Here, 1 analogues were synthesized to
      understand its interaction with DNMT. The indole, carboxylate, and phthalimide
      moieties were modified. Homologated and conformationally constrained analogues
      were prepared. The latter were synthesized from prolinohomotryptophan derivatives
      through a methodology based amino-zinc-ene-enolate cyclization. All compounds
      were tested for their ability to inhibit DNMT1 in vitro. Among them, constrained
      compounds 16-18 and NPys derivatives 10-11 were found to be at least 10-fold more
      potent than the reference compound. The cytotoxicity on the tumor DU145 cell line
      of the most potent inhibitors was correlated to their inhibitory potency.
      Finally, docking studies were conducted in order to understand their binding
      mode. This study provides insights for the design of the next-generation of DNMT
      inhibitors.

PMID- 24328114
TI  - Structure of glasses in the pseudobinary system Ga(2)Se(3)-GeSe(2): violation of
      chemical order and 8-N coordination rule.
AB  - Structure of glasses in the pseudobinary system Ga2Se3-GeSe2 with Ga2Se3 content
      ranging from 6.3 to 30 mol % is investigated using a combination of Raman and
      multinuclear ((71)Ga, (77)Se) solid state nuclear magnetic resonance (NMR)
      spectroscopy. The results indicate that the structure of these glasses consists
      primarily of a corner sharing network of (Ge/Ga)Se4 tetrahedra with some fraction
      of edge-sharing GeSe4 tetrahedra and of ethane-like (Se3)Ge-Ge(Se3) units, in
      which the Ga, Ge, and Se atoms adopt coordination numbers of 4, 4, and 2,
      respectively. As expected, the concentration of metal-metal bonds increases with
      addition of Ga2Se3 as the glass structure becomes too deficient in Se to satisfy
      the tetrahedral coordination of both Ga and Ge by Se atoms alone. These metal
      metal bonds are mostly limited to Ge-Ge homopolar bonds, indicating a violation
      of chemical order. At relatively high degrees of Se-deficiency, however,
      spectroscopic evidence suggests the formation of triply coordinated Se atoms as
      an alternate mechanism to accommodate the tetrahedral coordination of Ga and Ge
      atoms. This observation indicates a violation of the 8-N coordination rule and is
      reminiscent of oxygen triclusters in isoelectronic Al2O3-SiO2 glasses.
      Compositional variation of physical properties such as density, molar volume,
      optical band gap, glass transition temperature, and fragility are shown to be
      consistent with the proposed structural model. 

PMID- 24328116
TI  - Molecular dynamics studies on liquid-phase dynamics and structures of four
      different fluoropropenes and their binary mixtures with R-32 and CO2.
AB  - Fluoropropenes such as R-1234yf or R-1234ze(E) have attracted attention as low
      GWP (global warming potential) refrigerants, both as pure compounds but also to
      an increasing extent as components in refrigerant blends. In our earlier work
      [Raabe, G.; Maginn, E. J. J. Phys. Chem. B 2010, 114, 10133-10142 and Raabe, G.
      J. Phys. Chem. B 2012, 116, 5744-5751], we have introduced a transferable force
      field for different fluoropropene compounds. This molecular model has already
      been applied for predictive molecular simulation studies on the vapor-liquid
      phase equilibria in binary mixtures of the tetrafluoropropenes R-1234yf or R
      1234ze(E) with the difluoromethane R-32 and CO2. In this work we present
      molecular dynamics simulations on the liquid phase properties of the pure
      fluoropropenes R-1234yf, R-1234ze, R-1234ze(E), and R-1216 and their binary
      mixtures with CO2 and R-32. Our study covers temperatures from 273 to 313 K,
      pressures up to 3.5 MPa, and different mixture compositions. We provide
      predictions on the densities and transport properties of the pure compounds and
      the binary mixtures to complement experimental data. Additionally, we have
      analyzed radial and spatial distribution functions in the systems to gain insight
      into their microscopic structures and preferred interaction sites.

PMID- 24328115
TI  - Using single-turnover kinetics with osmotic stress to characterize the EcoRV
      cleavage reaction.
AB  - Type II restriction endonucleases require metal ions to specifically cleave DNA
      at canonical sites. Despite the wealth of structural and biochemical information,
      the number of Mg(2+) ions used for cleavage by EcoRV, in particular, at
      physiological divalent ion concentrations has not been established. In this work,
      we employ a single-turnover technique that uses osmotic stress to probe reaction
      kinetics between an initial specific EcoRV-DNA complex formed in the absence of
      Mg(2+) and the final cleavage step. With osmotic stress, complex dissociation
      before cleavage is minimized and the reaction rates are slowed to a convenient
      time scale of minutes to hours. We find that cleavage occurs by a two-step
      mechanism that can be characterized by two rate constants. The dependence of
      these rate constants on Mg(2+) concentration and osmotic pressure gives the
      number of Mg(2+) ions and water molecules coupled to each kinetic step of the
      EcoRV cleavage reaction. Each kinetic step is coupled to the binding 1.5-2.5
      Mg(2+) ions, the uptake of ~30 water molecules, and the cleavage of a DNA single
      strand. We suggest that each kinetic step reflects an independent, rate-limiting
      conformational change of each monomer of the dimeric enzyme that allows Mg(2+)
      ion binding. This modified single-turnover protocol has general applicability for
      metalloenzymes. 

PMID- 24328117
TI  - Revisiting the prospects of plastein: thermal and simulated gastric stability in
      relation to the antioxidative capacity of casein plastein.
AB  - Plastein, a product of protease-induced peptide aggregation, is thought to
      possess unique physical properties and bioactivity, although its formation,
      stability, and functional mechanisms remain unclear. This study demonstrates that
      plastein is formed from bovine casein peptides with Alcalase by hydrophobic and
      electrostatic interactions and less likely by covalent bonding. The peptide
      aggregation enhanced the Fe(III) reducing potential and decreased the Fe(II)
      chelating activity (p < 0.05) of casein peptides, but there was no difference in
      inhibition of Fe-induced linoleic acid peroxidation after plastein reaction. The
      casein plastein product retained its antioxidative activities after being heated
      at 100  degrees C. However, simulated gastric protease treatment with pepsin and
      pancreatic enzymes resulted in enhanced reducing potential and metal chelation of
      the casein plastein and reduction of the inhibitory effect on lipid peroxidation.
      It appears that the plasteins were disintegrated and further hydrolyzed by
      gastric proteases on the basis of the antioxidative capacity and RP-HPLC profile
      being similar to those of the casein hydrolysates. Therefore, plastein reaction
      may not confer metabolic stability or enhance the antioxidative capacity of
      casein peptides for prospective functional food applications. 

PMID- 24328118
TI  - Effectiveness of a segmental approach to climate policy.
AB  - Resistance to adopting a cap on greenhouse gas emissions internationally, and
      across various national contexts, has encouraged alternative climate change
      mitigation proposals. These proposals include separately targeting clean energy
      uptake and demand-side efficiency in individual end-use sectors, an approach to
      climate change mitigation which we characterize as segmental and technology
      centered. A debate has ensued on the detailed implementation of these policies in
      particular national contexts, but less attention has been paid to the general
      factors determining the effectiveness of a segmental approach to emissions
      reduction. We address this topic by probing the interdependencies of segmental
      policies and their collective ability to control emissions. First, we show for
      the case of U.S. electricity how the set of suitable energy technologies depends
      on demand-side efficiency, and changes with the stringency of climate targets.
      Under a high-efficiency scenario, carbon-free technologies must supply 60-80% of
      U.S. electricity demand to meet an emissions reduction target of 80% below 1990
      levels by midcentury. Second, we quantify the enhanced propensity to exceed any
      intended emissions target with this approach, even if goals are set on both the
      supply and demand side, due to the multiplicative accumulation of emissions
      error. For example, a 10% error in complying with separate policies on the demand
      and supply side would combine to result in a 20% error in emissions. Third, we
      discuss why despite these risks, the enhanced planning capability of a segmental
      approach may help counteract growing infrastructural inertia. The emissions
      reduction impediment due to infrastructural inertia is significant in the
      electricity sectors of each of the greatest emitters: China, the U.S., and
      Europe. Commonly cited climate targets are still within reach but, as we show,
      would require more than a 50% reduction in the carbon intensity of new power
      plants built in these regions over the next decade. 

PMID- 24328119
TI  - New powerful and oxidatively rugged dinuclear Ru water oxidation catalyst:
      control of mechanistic pathways by tailored ligand design.
AB  - A new powerful and oxidatively rugged pyrazolate-based water oxidation catalyst
      of formula {[Ru(II)(py-SO3)2(H2O)]2(MU-Mebbp)}(-), 1(H2O)2(-), has been prepared
      and thoroughly characterized spectroscopically and electrochemically. This new
      catalyst has been conceived based on a specific ligand tailoring design, so that
      its performance has been systematically improved. It was also demonstrated how
      subtle ligand modifications cause a change in the O-O bond formation mechanism,
      thus revealing the close activation energy barriers associated with each pathway.

PMID- 24328120
TI  - 2,2,6,6-Tetramethylpiperidine-catalyzed, ortho-selective chlorination of phenols
      by sulfuryl chloride.
AB  - 2,2,6,6-Tetramethylpiperidine (TMP)-catalyzed (1-10%) chlorinations of phenols by
      SO2Cl2 in aromatic solvents are more ortho selective than with primary and less
      hindered secondary amine catalysts. Ortho-selective chlorination is successful
      even with electron deficient phenols such as 2-hydroxybenzaldehyde and 2'
      hydroxyacetophenone. Notably, ortho selectivity increases with the reaction
      temperature. On the other hand, tetraalkylammonium chloride-catalyzed
      chlorinations are moderately para selective. 

PMID- 24328121
TI  - Synthesis, characterization, and computational study of complexes containing
      Pt...H hydrogen bonding interactions.
AB  - Complexes [Pt(C6F5)(bzq)L] (bzq = 7,8-benzoquinolinate; L = 8-hydroxyquinoline,
      hqH (1); 2-methyl-8-hydroxyquinoline, hqH' (2)) have been prepared by replacing
      the labile acetone ligand in the starting material [Pt(C6F5)(bzq)(Me2CO)]. The
      (1)H NMR spectra of 1 and 2 show that the signals attributable to the hydroxyl
      proton of the hqH or hqH' ligands are displaced downfield 2.64 ppm for 1 and 2.74
      ppm for 2 with respect to the respective free ligands. Moreover, in both
      complexes the signals present platinum satellites with J(Pt,H) coupling constant
      of 67.0 Hz for 1 and 80.6 Hz for 2. All these features are indicative of the
      existence of Pt...H-O hydrogen bonds in solution for these complexes. The
      structures of complexes 1 and 2 have been established by an X-ray diffraction
      study and allow us to confirm the existence of these interactions in the solid
      state too. Thus, in both cases the hydroxyl hydrogen atom is pointing toward the
      metal center, and the measured geometric parameters involving this hydrogen are
      Pt-H = 2.09(4) A, O-H = 0.94(4) A, Pt-H-O 162(4) degrees , for 1, and Pt-H =
      2.10(4) A, O-H = 0.91(4) A, Pt-H-O 162(4) degrees , for 2, all of which are fully
      compatible with a hydrogen bond system. Complexes 1 and 2 and the analogues
      [Pt(C6F5)3(hqH)](-) (A) and [Pt(C6F5)3(hqH')](-) (B), prepared some time ago in
      our laboratory and also showing Pt...H-O hydrogen bonds, have been the object of
      theoretical calculations to obtain better insight into the Pt...H interactions.
      Their density functional theory (DFT) calculated structures show excellent
      agreement with the X-ray determined ones (1, 2, and B). Topological analyses of
      the electron density function (rho(r)) have been performed on the four complexes
      according to Bader's Atoms In Molecules theory. These analyses reveal a bond path
      that relates the platinum atom and the hydroxyl hydrogen atom, as well as the
      corresponding bond critical points. The values of the Laplacian ?(2)rho(r) and
      local energy density H(r) indicate that these are closed shell, electrostatic
      interactions, but with partial covalence. The deprotonation of the OH fragment in
      1 and 2 with BuLi leads to the formation of the unexpected trinuclear complexes
      (NBu4)[Li{Pt(C6F5)(bzq)(L)}2] (L = hq (3), hq' (4)). The X-ray structures of
      these have shown a change in the coordination of the deprotonated hq and hq',
      which are now bonded to the Pt atoms through their O atoms, and which are
      bridging the Pt and Li metal atoms. 

PMID- 24328122
TI  - Quantum chemistry investigation of fluorinated polymer systems of industrial
      interest.
AB  - In this work, the free-radical polymerization (FRP) of widely used fluorinated
      monomers was investigated. Computational studies were conducted to assess the FRP
      kinetics of each binary copolymerization between vinylidene fluoride (VDF),
      hexafluoropropylene (HFP), and tetrafluoroethylene (TFE). More specifically, all
      calculations were performed using density functional theory (DFT), and the B3LYP
      level of theory was used to optimize structures and determine absolute minimum
      energy geometries, whereas the electronic energies were estimated using B3LYP/6
      31G(d,p) as well as a higher level of theory, MPWB1K/6-31G(d,p). Transition state
      theory was employed to determine kinetic parameters according to the terminal
      model of copolymerization. The homopolymerization of VDF and all of its
      corresponding copolymerizations were investigated by taking into account every
      possible propagation reaction (head to head, head to tail, tail to tail, head to
      monomer, tail to monomer, etc.) to estimate the Arrhenius parameters for each
      system. This study provides the estimation of a large set of rate coefficients,
      which gives detailed pictures of the specific copolymerization systems examined
      and is highly valuable to generate a comprehensive overview of the polymerization
      kinetics of relevant fluorinated monomers. 

PMID- 24328123
TI  - Solution processable high dielectric constant nanocomposites based on ZrO2
      nanoparticles for flexible organic transistors.
AB  - A solution-based strategy for fabrication of high dielectric constant (kappa)
      nanocomposites for flexible organic field effect transistors (OFETs) has been
      developed. The nanocomposite was composed of a high-kappa polymer, cyanoethyl
      pullulan (CYELP), and a high-kappa nanoparticle, zirconium dioxide (ZrO2).
      Organic field effect transistors (OFETs) based on neat CYELP exhibited anomalous
      behavior during device operation, such as large hysteresis and variable threshold
      voltages, which yielded inconsistent devices and poor electrical characteristics.
      To improve the stability of the OFET, we introduced ZrO2 nanoparticles that bind
      with residual functional groups on the high-kappa polymer, which reduces the
      number of charge trapping sites. The nanoparticles, which serve as physical cross
      links, reduce the hysteresis without decreasing the dielectric constant. The
      dielectric constant of the nanocomposites was tuned over the range of 15.6-21 by
      varying the ratio of the two components in the composite dielectrics, resulting
      in a high areal capacitance between 51 and 74 nF cm(-2) at 100 kHz and good
      insulating properties of a low leakage current of 1.8 * 10(-6) A cm(-2) at an
      applied voltage of -3.5 V (0.25 MV cm(-1)). Bottom-gate, top-contact (BGTC) low
      operating voltage p-channel OFETs using these solution processable high-kappa
      nanocomposites were fabricated by a contact film transfer (CFT) technique with
      poly(3-hexylthiophene) (P3HT) as the charge transport layer. Field effect
      mobilities as high as 0.08 cm(2) V(-1) s(-1) and on/off current ratio of 1.2 *
      10(3) for P3HT were measured for devices using the high-kappa dielectric ZrO2
      nanocomposite. These materials are promising for generating solution coatable
      dielectrics for low cost, large area, low operating voltage flexible transistors.

PMID- 24328124
TI  - Modulation of reactive oxygen species photogeneration of bacteriopheophorbide a
      derivatives by exocyclic E-ring opening and charge modifications.
AB  - With the knowledge that the dominant photodynamic therapy (PDT) mechanism of 1a
      (WST09) switched from type 2 to type 1 for 1b (WST11) upon taurine-driven E-ring
      opening, we hypothesized that taurine-driven E-ring opening of
      bacteriochlorophyll derivatives and net-charge variations would modulate reactive
      oxygen species (ROS) photogeneration. Eight bacteriochlorophyll a derivatives
      were synthesized with varying charges that either contained the E ring (2a-5a) or
      were synthesized by taurine-driven E-ring opening (2b-5b). Time-dependent density
      functional theory (TDDFT) modeling showed that all derivatives would be type 2
      PDT-active, and ROS-activated fluorescent probes were used to investigate the
      photogeneration of a combination of type 1 and type 2 PDT ROS in organic- and
      aqueous-based solutions. These investigations validated our predictive modeling
      calculations and showed that taurine-driven E-ring opening and increasing
      negative charge generally enhanced ROS photogeneration in aqueous solutions. We
      propose that these structure-activity relationships may provide simple strategies
      for designing bacteriochlorins that efficiently generate ROS upon
      photoirradiation. 

PMID- 24328125
TI  - Quantification of transgene-derived double-stranded RNA in plants using the
      QuantiGene nucleic acid detection platform.
AB  - The expanding use of RNA interference (RNAi) in agricultural biotechnology
      necessitates tools for characterizing and quantifying double-stranded RNA (dsRNA)
      containing transcripts that are expressed in transgenic plants. We sought to
      detect and quantify such transcripts in transgenic maize lines engineered to
      control western corn rootworm (Diabrotica virgifera virgifera LeConte) via
      overexpression of an inverted repeat sequence bearing a portion of the putative
      corn rootworm orthologue of yeast Snf7 (DvSnf7), an essential component of insect
      cell receptor sorting. A quantitative assay was developed to detect DvSnf7 sense
      strand-containing dsRNA transcripts that is based on the QuantiGene Plex 2.0 RNA
      assay platform from Affymetrix. The QuantiGene assay utilizes cooperative binding
      of multiple oligonucleotide probes with specificity for the target sequence
      resulting in exceptionally high assay specificity. Successful implementation of
      this assay required heat denaturation in the presence of the oligonucleotide
      probes prior to hybridization, presumably to dissociate primary transcripts
      carrying the duplex dsRNA structure. The dsRNA assay was validated using a
      strategy analogous to the rigorous enzyme-linked immunosorbent assay evaluations
      that are typically performed for foreign proteins expressed in transgenic plants.
      Validation studies indicated that the assay is sensitive (to 10 pg of dsRNA/g of
      fresh tissue), highly reproducible, and linear over ~2.5 logs. The assay was
      validated using purified RNA from multiple maize tissue types, and studies
      indicate that the assay is also quantitative in crude tissue lysates. To the best
      of our knowledge, this is the first report of a non-polymerase chain reaction
      based quantitative assay for dsRNA-containing transcripts, based on the use of
      the QuantiGene technology platform, and will broadly facilitate characterization
      of dsRNA in biological and environmental samples. 

PMID- 24328126
TI  - Effect of charged amino acid side chain length on lateral cross-strand
      interactions between carboxylate-containing residues and lysine analogues in a
      beta-hairpin.
AB  - beta-Sheets are one of the fundamental three-dimensional building blocks for
      protein structures. Oppositely charged amino acids are frequently observed
      directly across one another in antiparallel sheet structures, suggesting the
      importance of cross-strand ion pairing interactions. Despite the apparent
      electrostatic nature of ion pairing interactions, the charged amino acids Asp,
      Glu, Arg, Lys have different numbers of hydrophobic methylenes linking the
      charged functionality to the backbone. Accordingly, the effect of charged amino
      acid side chain length on cross-strand ion pairing interactions at lateral non
      hydrogen bonded positions was investigated in a beta-hairpin motif. The
      negatively charged residues with a carboxylate (Asp, Glu, Aad in increasing
      length) were incorporated at position 4, and the positively charged residues with
      an ammonium (Dap, Dab, Orn, Lys in increasing length) were incorporated at
      position 9. The fraction folded population and folding free energy were derived
      from the chemical shift deviation data. Double mutant cycle analysis was used to
      determine the interaction energy for the potential lateral ion pairs. Only the
      Asp/Glu-Dap interactions with shorter side chains and the Aad-Orn/Lys
      interactions with longer side chains exhibited stabilizing energetics, mostly
      relying on electrostatics and hydrophobics, respectively. This suggested the need
      for length matching of the interacting residues to stabilize the beta-hairpin
      motif. A survey of a nonredundant protein structure database revealed that the
      statistical sheet pair propensity followed the trend Asp-Lys < Glu-Lys, also
      implying the need for length matching of the oppositely charged residues. 

PMID- 24328127
TI  - Assembly of an activated rhodopsin-transducin complex in nanoscale lipid
      bilayers.
AB  - The formation and characterization of an activated complex of the visual pigment
      rhodopsin and its downstream signaling partner transducin have been the subject
      of intense focus by several research groups. While the subunit composition of the
      activated complex is still the subject of some controversy, our laboratory [Xie,
      G., D'Antona, A. M., Edwards, P. C., Fransen, M., Standfuss, J., Schertler, G. F.
      X., and Oprian, D. D. (2011) Biochemistry 50, 10399-10407] and that of Ernst et
      al. [Ernst, O. P., Gramse, V., Kolbe, M., Hofmann, K. P., and Heck, M. (2007)
      Proc. Natl. Acad. Sci. U.S.A. 104, 10859-10864] find that the two proteins are
      present in a 1/1 molar ratio. Unfortunately, these data could not distinguish a
      ratio of 1/1 from ratios of 2/2, 3/3, etc. For this reason, we reinvestigated the
      issue of stoichiometry of the activated complex, exploiting the ability of
      Nanodisc lipid bilayers to isolate single molecules of rhodopsin. We show here
      that the purified complex in Nanodiscs contains an activated rhodopsin with a
      covalently bound all-trans-retinal chromophore, that transducin has an empty
      nucleotide-binding pocket, that the isolated complex is active and dissociates
      upon addition of guanine nucleotide, and that the stoichiometry corresponds to
      exactly one molecule of rhodopsin and one molecule of transducin. 

PMID- 24328128
TI  - Impact of the nonvolatile wine matrix composition on the in vivo aroma release
      from wines.
AB  - The impact of the nonvolatile wine matrix composition on the retronasal aroma
      release of four volatile compounds added to different types of wines has been
      evaluated. For this purpose, a tailor-made retronasal aroma trapping device
      (RATD) was used to entrap the exhaled breath of six panelists previously trained
      in a specific consumption procedure. Five wines of different composition (white
      wine, sparkling white wine, young red wine, aged red wine, and a sweet wine) were
      evaluated. Prior to the evaluation, with the exception of the sweet wine, the
      wines were adjusted to the same ethanol content and aromatized with a mixture of
      four target volatile compounds. Aroma release data were submitted to multivariate
      statistical analysis in order to relate wine chemical composition and aroma
      release during wine drinking. Results showed interindividual differences and a
      clustering of panelists among lower and higher aroma releasers, which was in
      agreement to the differences in their breathing capacity. A significant influence
      of the matrix composition in the low aroma releasers group during wine
      consumption was observed. The consumption of red wines provoked a significantly
      higher aroma release than the consumption of white and sweet wines. From the
      chemical composition determined in the wine samples (pH, total acidity, total
      polyphenols, neutral polysaccharides, residual sugar, and nitrogenous compounds),
      the amount of total polyphenols was better correlated with the observed effect. 

PMID- 24328129
TI  - Difference of carboxybetaine and oligo(ethylene glycol) moieties in altering
      hydrophobic interactions: a molecular simulation study.
AB  - Polycarboxybetaine and poly(ethylene glycol) materials resist nonspecific protein
      adsorption but differ in influencing biological functions such as enzymatic
      activity. To investigate this difference, we studied the influence of
      carboxybetaine and oligo(ethylene glycol) moieties on hydrophobic interactions
      using molecular simulations. We employed a model system composed of two non-polar
      plates and studied the potential of mean force of plate-plate association in
      carboxybetaine, (ethylene glycol)4, and (ethylene glycol)2 solutions using well
      tempered metadynamics simulations. Water, trimethylamine N-oxide, and urea
      solutions were used as reference systems. We analyzed the variation of the
      potential of mean force in various solutions to study how carboxybetaine and
      oligo(ethylene glycol) moieties influence the hydrophobic interactions. To study
      the origin of their influence, we analyzed the normalized distributions of
      moieties and water molecules using molecular dynamics simulations. The simulation
      results showed that oligo(ethylene glycol) moieties repel water molecules away
      from the non-polar plates and weaken the hydrophobic interactions. Carboxybetaine
      moieties do not repel water molecules away from the plates and therefore do not
      influence the hydrophobic interactions. 

PMID- 24328130
TI  - Transition metal associations with primary biological particles in sea spray
      aerosol generated in a wave channel.
AB  - In the ocean, breaking waves generate air bubbles which burst at the surface and
      eject sea spray aerosol (SSA), consisting of sea salt, biogenic organic species,
      and primary biological aerosol particles (PBAP). Our overall understanding of
      atmospheric biological particles of marine origin remains poor. Here, we perform
      a control experiment, using an aerosol time-of-flight mass spectrometer to
      measure the mass spectral signatures of individual particles generated by
      bubbling a salt solution before and after addition of heterotrophic marine
      bacteria. Upon addition of bacteria, an immediate increase occurs in the fraction
      of individual particle mass spectra containing magnesium, organic nitrogen, and
      phosphate marker ions. These biological signatures are consistent with 21% of the
      supermicrometer SSA particles generated in a previous study using breaking waves
      in an ocean-atmosphere wave channel. Interestingly, the wave flume mass spectral
      signatures also contain metal ions including silver, iron, and chromium. The
      nascent SSA bioparticles produced in the wave channel are hypothesized to be as
      follows: (1) whole or fragmented bacterial cells which bioaccumulated metals
      and/or (2) bacteria-derived colloids or biofilms which adhered to the metals.
      This study highlights the potential for transition metals, in combination with
      specific biomarkers, to serve as unique indicators for the presence of marine
      PBAP, especially in metal-impacted coastal regions. 

PMID- 24328131
TI  - Optimization of a yeast RNA interference system for controlling gene expression
      and enabling rapid metabolic engineering.
AB  - Reduction of endogenous gene expression is a fundamental operation of metabolic
      engineering, yet current methods for gene knockdown (i.e., genome editing) remain
      laborious and slow, especially in yeast. In contrast, RNA interference allows
      facile and tunable gene knockdown via a simple plasmid transformation step,
      enabling metabolic engineers to rapidly prototype knockdown strategies in
      multiple strains before expending significant cost to undertake genome editing.
      Although RNAi is naturally present in a myriad of eukaryotes, it has only been
      recently implemented in Saccharomyces cerevisiae as a heterologous pathway and so
      has not yet been optimized as a metabolic engineering tool. In this study, we
      elucidate a set of design principles for the construction of hairpin RNA
      expression cassettes in yeast and implement RNA interference to quickly identify
      routes for improvement of itaconic acid production in this organism. The approach
      developed here enables rapid prototyping of knockdown strategies and thus
      accelerates and reduces the cost of the design-build-test cycle in yeast. 

PMID- 24328132
TI  - Mixing state of size-selected submicrometer particles in the Arctic in May and
      September 2012.
AB  - Aerosols have been associated with large uncertainties in estimates of the
      radiation budget and cloud formation processes in the Arctic. This paper reports
      the results of a study of in situ measurements of hygroscopicity, fraction of
      volatile species, mixing state, and off-line morphological and elemental analysis
      of Aitken and accumulation mode particles in the Arctic (Ny-Alesund, Svalbard) in
      May and September 2012. The accumulation mode particles were more abundant in May
      than in September. This difference was due to more air mass flow from lower
      latitude continental areas, weaker vertical mixing, and less wet scavenging in
      May than in September, which may have led to a higher amount of long-range
      transport aerosols entering the Arctic in the spring. The Aitken mode particles
      observed intermittently in May were produced by nucleation, absent significant
      external mixing, whereas the accumulation mode particles displayed significant
      external mixing. The occurrence of an external mixing state was observed more
      often in May than in September and more often in accumulation mode particles than
      in Aitken mode particles, and it was associated more with continental air masses
      (Siberian) than with other air masses. The external mixing of the accumulation
      mode particles in May may have been caused by multiple sources (i.e., long-range
      transport aerosols with aging and marine aerosols). These groups of externally
      mixed particles were subdivided into different mixing structures (internal
      mixtures of predominantly sulfates and volatile organics without nonvolatile
      species and internal mixtures of sulfates and nonvolatile components, such as sea
      salts, minerals, and soot). The variations in the mixing states and chemical
      species of the Arctic aerosols in terms of their sizes, air masses, and seasons
      suggest that the continuous size-dependent measurements observed in this study
      are useful for obtaining better estimates of the effects of these aerosols on
      climate change. 

PMID- 24328133
TI  - Enantioselective total syntheses of leuconolam-leuconoxine-mersicarpine group
      monoterpene indole alkaloids.
AB  - A unified strategy allowing enantioselective total syntheses of (-)-mersicarpine,
      (-)-scholarisine G, (+)-melodinine E, (-)-leuconoxine, and (-)-leuconolam from a
      common cyclohexenone derivative was reported. The Suzuki-Miyaura reaction was
      used to couple two simple fragments incorporating the key elements for total
      synthesis, and unprecedented oxidation/reduction/cyclization processes were
      developed that converted the substituted cyclohexenone to either a mersicarpine
      or leuconoxine skeleton. In a reverse biomimetic synthesis fashion, (+)
      melodinine E was converted to (-)-leuconolam under acidic conditions. 

PMID- 24328134
TI  - Iron-catalyzed arylalkoxycarbonylation of N-aryl acrylamides with carbazates.
AB  - A novel arylalkoxycarbonylation of N-aryl acrylamides with carbazates leading to
      alkoxycarbonylated oxindoles has been developed. The reported reactions employ
      economical and environmentally benign FeCl2.4H2O as a catalyst and easily
      accessible and safe carbazates as alkoxycarbonyl radical precursors. 

PMID- 24328135
TI  - Cu(II)- and Mn(III)-porphyrin-derived oligomeric multianions: structures and
      photoelectron spectra.
AB  - We present structures and photoelectron spectra of Mn(III) and Cu(II) meso
      tetra(4-sulfonatophenyl)porphyrin (TPPS) multianions, as well as of homomolecular
      dimers and trimers thereof. The structural assignments are based on a combination
      of mass spectrometry, ion mobility measurements, and semiempirical as well as
      density functional theory (DFT) calculations. Depending on the type of central
      metal atom, two completely different dimer structural motifs are found. With a
      central Mn(III), the monomeric units are connected via sulfonic-acid-manganese
      bonds resulting in a tilted stack arrangement of porphyrin rings. With Cu(II) as
      the central atom, the sulfonic acid groups preferentially bind to the sodium
      counterions, resulting in a flat dimer structure with coplanar porphyrins.
      Photoelectron spectra were recorded for monomers, dimers, and trimers, each in a
      number of different negative charge states as determined by protonation degree
      (+nH). In some cases, e.g., [Cu(II)TPPS](4-), [(Mn(III)TPPS)2 + H](5-), and
      [(Mn(III)TPPS)3 + 3H](6-), we observe electron detachment energies close to zero,
      or even slightly negative. In all cases, we find a large repulsive Coulomb
      barrier. The observed trends in detachment energies can be interpreted in terms
      of a simple electrostatic model. 

PMID- 24328137
TI  - Synthesis, crystal structures, magnetic, and thermal properties of divalent metal
      formate-formamide layered compounds.
AB  - A series of layered divalent metal formate compounds, [M(HCOO)2(HCONH2)2] (M = Mn
      (1Mn), Ni (2Ni), Cu(3Cu), Zn(4Zn), Mg(5Mg)), have been prepared by solvothermal
      synthesis and their room temperature (RT) and low-temperature (LT) crystal
      structures, and thermal and magnetic properties determined. All the compounds
      contain octahedral metal ions connected by four anti-anti formato ligands to form
      (4,4) nets with the composition of M(HCOO)2. The oxygen atoms from two
      coordinating formamide ligands above and below the layer complete the MO6
      distorted octahedral coordination. Order-disorder phase transformations involving
      the formamide ligands were observed in the 1Mn, 2Ni, and 4Zn compounds. Like
      transitions in related formate structures with perovskite like topology, the
      transitions correspond to the ordering of the amine groups of the terminating
      formamide ligands which are disordered at ambient temperature. The magnetic
      properties of the three magnetic members of the series 1Mn, 2Ni, and 3Cu were
      investigated using microcrystalline samples, over the temperature range of 2 K
      300 K under different applied fields. All compounds belong to antiferromagnetic
      square lattices with S = 5/2, 1, and 1/2. Exchange constants for a nearest
      neighbor model are presented here. Specific heat measurements indicate magnetic
      long-range order at lower temperatures, S = 5/2 (antiferromagnetic) and S = 1
      (ferrimagnetic). 

PMID- 24328136
TI  - Identification of a selective polymerase enables detection of N(6)
      methyladenosine in RNA.
AB  - N(6)-methyladenosine (m(6)A) is the most abundant mRNA modification and has
      important links to human health. While recent studies have successfully
      identified thousands of mammalian RNA transcripts containing the modification, it
      is extremely difficult to identify the exact location of any specific m(6)A. Here
      we have identified a polymerase with reverse transcriptase activity (from Thermus
      thermophilus) that is selective by up to 18-fold for incorporation of thymidine
      opposite unmodified A over m(6)A. We show that the enzyme can be used to locate
      and quantify m(6)A in synthetic RNAs by analysis of pausing bands, and have used
      the enzyme in tandem with a nonselective polymerase to locate the presence and
      position of m(6)A in high-abundance cellular RNAs. By this approach we
      demonstrate that the long-undetermined position of m(6)A in mammalian 28S rRNA is
      nucleotide 4190. 

PMID- 24328138
TI  - Toxins in botanical dietary supplements: blue cohosh components disrupt cellular
      respiration and mitochondrial membrane potential.
AB  - Certain botanical dietary supplements have been associated with idiosyncratic
      organ-specific toxicity. Similar toxicological events, caused by drug-induced
      mitochondrial dysfunction, have forced the withdrawal or U.S. FDA "black box"
      warnings of major pharmaceuticals. To assess the potential mitochondrial
      liability of botanical dietary supplements, extracts from 352 authenticated plant
      samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were
      evaluated for the ability to disrupt cellular respiration. Blue cohosh
      (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic
      activity. Used by some U.S. midwives to help induce labor, blue cohosh has been
      associated with perinatal stroke, acute myocardial infarction, congestive heart
      failure, multiple organ injury, and neonatal shock. The potential link between
      mitochondrial disruption and idiosyncratic herbal intoxication prompted further
      examination. The C. thalictroides methanol extract and three saponins, cauloside
      A (1), saponin PE (2), and cauloside C (3), exhibited concentration- and time
      dependent mitochondriotoxic activities. Upon treatment, cell respiration rate
      rapidly increased and then dramatically decreased within minutes. Mechanistic
      studies revealed that C. thalictroides constituents impair mitochondrial function
      by disrupting membrane integrity. These studies provide a potential etiological
      link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic
      organ damage. 

PMID- 24328139
TI  - Total synthesis of the antitumor antibiotic (+/-)-streptonigrin: first- and
      second-generation routes for de novo pyridine formation using ring-closing
      metathesis.
AB  - The total synthesis of (+/-)-streptonigrin, a potent tetracyclic aminoquinoline
      5,8-dione antitumor antibiotic that reached phase II clinical trials in the
      1970s, is described. Two routes to construct a key pentasubstituted pyridine
      fragment are depicted, both relying on ring-closing metathesis but differing in
      the substitution and complexity of the precursor to cyclization. Both routes are
      short and high yielding, with the second-generation approach ultimately
      furnishing (+/-)-streptonigrin in 14 linear steps and 11% overall yield from
      inexpensive ethyl glyoxalate. This synthesis will allow for the design and
      creation of druglike late-stage natural product analogues to address
      pharmacological limitations. Furthermore, assessment of a number of chiral
      ligands in a challenging asymmetric Suzuki-Miyaura cross-coupling reaction has
      enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to
      be prepared for the first time. 

PMID- 24328140
TI  - von Willebrand factor antagonizes nitric oxide synthase to promote insulin
      resistance during hypoxia.
AB  - Hypoxic respiratory diseases or hypoxia exposures are frequently accompanied by
      glucose intolerance and impaired nitric oxide (NO) availability. However, the
      molecular mechanism responsible for impaired NO production and insulin resistance
      (IR) during hypoxia remains obscure. In this study, we investigated the possible
      mechanism of impaired NO production and IR during hypoxia in a mouse model. Mice
      were exposed to hypoxia for different periods of time (0-24 h), and parameters of
      IR and endothelial dysfunctions were analyzed. Exposure to hypoxia resulted in a
      time-dependent increase in IR as well as multimeric forms of von Willebrand
      factor (vWF) and subsequently a decrease in eNOS activity. Preincubation with
      plasma of hypoxia-exposed animals (different time points) or human vWF inhibited
      insulin-induced NO production in a dose-dependent manner; larger doses of insulin
      reversed the effect. In contrast, preincubation of vWF-immunodepleted plasma
      failed to inhibit insulin-induced NO production, whereas vWF immunoneutralization
      abolished the effect of hypoxia-induced IR and D-[U-(14)C]glucose uptake.
      Furthermore, the interactions between vWF and eNOS were studied by far-Western
      blotting, co-immunoprecipitation, and surface plasma resonance spectroscopy.
      Kinetic analyses showed that the dissociation constant (KD), inhibitory constant
      (Ki), and half-maximal inhibitory concentration (IC50) were 1.79 * 10(-8) M, 250
      pM, and 18.31 pM, respectively, suggesting that vWF binds to eNOS with a high
      affinity and greater efficacy for activator (insulin) inhibition. These results
      indicated that vWF, an antagonist of eNOS, inhibits insulin-induced NO production
      and causes IR.

PMID- 24328141
TI  - Unified description of urea denaturation: backbone and side chains contribute
      equally in the transfer model.
AB  - After studying protein denaturation by urea for many decades, conflicting views
      of the role of the side chains and the backbone have emerged; many results
      suggest that urea denatures by enhancing the solubility of both the side chains
      and the backbone, but the frequently applied transfer model (TM) so far ascribes
      denaturation exclusively to urea's action on the backbone. We use molecular
      dynamics simulations to rigorously test one of the TM's key assumptions, the
      proportionality of a molecule's transfer free energy (TFE) and its solvent
      accessible surface. The performance of the TM as it is usually implemented turns
      out to be unsatisfactory, but the proportionality is satisfied very well after an
      inconsistency in the treatment of the backbone contribution is corrected. This
      inconsistency has so far gone unnoticed as it was obscured by a compensating
      error in the side-chain group TFEs used so far. The revised "universal backbone"
      TM presented in this work shows excellent accuracy in the prediction of
      experimental m values of a set of 36 proteins. It also settles the conflicting
      views regarding the role of the side chains because it predicts that both the
      side chains and the backbone on average contribute favorably to denaturation by
      urea. 

PMID- 24328142
TI  - Improving the gene-regulation ability of small RNAs by scaffold engineering in
      Escherichia coli.
AB  - Noncoding small RNAs are involved in transcriptional and post-transcriptional
      gene regulation of target mRNAs by modulating mRNA elongation, stability, or
      translational efficiency. Many natural trans-encoded small RNAs contain a
      scaffold that allows binding of the RNA chaperone protein Hfq for conditional
      gene regulation. Here, we improved the gene regulation abilities of small RNAs by
      directly fusing the natural Escherichia coli trans-encoded small RNA-derived
      scaffolds, including Hfq-binding and rho-independent transcription terminator
      sequences, to the 3' end of the small RNAs that mediate RNA-based gene
      regulation. As target small RNAs to improve their gene regulation abilities, we
      selected small RNAs of artificial post-transcriptional riboregulators and
      transcriptional attenuators. Four different small RNA scaffolds were fused to the
      riboregulator and attenuator-derived small RNAs. Mutations were introduced into
      the best small RNA scaffold to improve its gene-regulation ability further. As a
      result, mutations predicted to stabilize the secondary structures of the small
      RNA scaffolds dramatically increased its ability to regulate gene expression of
      both the post-transcriptional riboregulator and transcriptional attenuator
      systems. We believe our engineered small RNA scaffolds are applicable to other
      RNA regulators for improving regulatory activity, and engineered small RNA
      scaffolds may present a valuable strategy to regulate target gene expression
      strongly. 

PMID- 24328143
TI  - SOA formation potential of emissions from soil and leaf litter.
AB  - Soil and leaf litter are significant global sources of small oxidized volatile
      organic compounds, VOCs (e.g., methanol and acetaldehyde). They may also be
      significant sources of larger VOCs that could act as precursors to secondary
      organic aerosol (SOA) formation. To investigate this, soil and leaf litter
      samples were collected from the University of Idaho Experimental Forest and
      transported to the laboratory. There, the VOC emissions were characterized and
      used to drive SOA formation via dark, ozone-initiated reactions. Monoterpenes
      dominated the emission profile with emission rates as high as 228 MUg-C m(-2) h(
      1). The composition of the SOA produced was similar to biogenic SOA formed from
      oxidation of ponderosa pine emissions and alpha-pinene. Measured soil and litter
      monoterpene emission rates were compared with modeled canopy emissions. Results
      suggest surface soil and litter monoterpene emissions could range from 12 to 136%
      of canopy emissions in spring and fall. Thus, emissions from leaf litter may
      potentially extend the biogenic emissions season, contributing to significant
      organic aerosol formation in the spring and fall when reduced solar radiation and
      temperatures reduce emissions from living vegetation. 

PMID- 24328144
TI  - Cleaved and missed sites for trypsin, lys-C, and lys-N can be predicted with high
      confidence on the basis of sequence context.
AB  - Trypsin, Lys-C, and Lys-N are the most broadly used enzymes in proteomics. Here,
      on the basis of large-scale peptide mass spectrometry (MS) data sets, an approach
      is described to confidently identify missed cleavage sites in either
      phosphorylated or unmodified substrates for these three proteases, or any
      protease, on the basis of side chain species present within 15 residues of the
      cleavage-specificity residue. Previously known effects of proline, negatively
      charged side chains, and phospho-modified residues have been quantified, and
      additional side chain effects were noted. By applying a set of quantitative side
      chain rules established for each of the three proteases, scissile and nonscissile
      sites could be established, on the basis of protein sequence alone, with near
      certainty for Lys-C, and with a high degree of confidence for trypsin or Lys-N.
      These rules were applicable to orthogonal peptide data sets, including the two
      largest in the PeptideAtlas database. The approach described here facilitates the
      comprehensive modeling of substrate recognition in proteolysis. 

PMID- 24328146
TI  - Terazulene: a high-performance n-type organic field-effect transistor based on
      molecular orbital distribution control.
AB  - We present herein a linear expanded pi-conjugation system comprising azulene
      units: 2,6':2',6"-terazulene. This simple hydrocarbon exhibits excellent n-type
      transistor performance with an electron mobility of up to 0.29 cm(2) V(-1) s(-1).
      The lowest unoccupied molecular orbital (LUMO) is well distributed over the
      entire molecule, whereas the highest occupied molecular orbital (HOMO) is
      localized at one end. These findings indicate a disadvantage of hole carrier
      transport and an advantage of n-type-specific transport behavior. This system
      presents an unconventional concept: polarity control of OFET by molecular orbital
      distribution control. 

PMID- 24328145
TI  - Ara h 6 complements Ara h 2 as an important marker for IgE reactivity to peanut.
AB  - The similarities of two major peanut allergens, Ara h 2 and Ara h 6, in molecular
      size, amino acid sequence, and structure have made it difficult to obtain natural
      Ara h 6 free of Ara h 2. The objectives of this study were to purify natural Ara
      h 6 that is essentially free of Ara h 2 and to compare its IgE reactivity and
      potency in histamine release assays to Ara h 2. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of the highly purified allergen (<0.01% Ara h
      2) revealed a single 14.5 kD band, and the identity of Ara h 6 was confirmed by
      liquid chromatography-tandem mass spectrometry. Ara h 6 showed a higher
      seroprevalence in chimeric IgE enzyme-linked immunosorbent assay (n = 54) but a
      weaker biological activity in basophil histamine release assays than Ara h 2.
      Purified Ara h 6 will be useful for diagnostic IgE antibody assays as well as
      molecular and cellular studies to investigate the immunological mechanisms of
      peanut allergy. 

PMID- 24328147
TI  - Dielectric barrier discharge carbon atomic emission spectrometer: universal GC
      detector for volatile carbon-containing compounds.
AB  - It was found that carbon atomic emission can be excited in low temperature
      dielectric barrier discharge (DBD), and an atmospheric pressure, low power
      consumption, and compact microplasma carbon atomic emission spectrometer (AES)
      was constructed and used as a universal and sensitive gas chromatographic (GC)
      detector for detection of volatile carbon-containing compounds. A concentric DBD
      device was housed in a heating box to increase the plasma operation temperature
      to 300  degrees C to intensify carbon atomic emission at 193.0 nm. Carbon
      containing compounds directly injected or eluted from GC can be decomposed,
      atomized, and excited in this heated DBD for carbon atomic emission. The
      performance of this new optical detector was first evaluated by determination of
      a series of volatile carbon-containing compounds including formaldehyde, ethyl
      acetate, methanol, ethanol, 1-propanol, 1-butanol, and 1-pentanol, and absolute
      limits of detection (LODs) were found at a range of 0.12-0.28 ng under the
      optimized conditions. Preliminary experimental results showed that it provided
      slightly higher LODs than those obtained by GC with a flame ionization detector
      (FID). Furthermore, it is a new universal GC detector for volatile carbon
      containing compounds that even includes those compounds which are difficult to
      detect by FID, such as HCHO, CO, and CO2. Meanwhile, hydrogen gas used in
      conventional techniques was eliminated; and molecular optical emission detection
      can also be performed with this GC detector for multichannel analysis to improve
      resolution of overlapped chromatographic peaks of complex mixtures. 

PMID- 24328149
TI  - The role of the amino acid-derived side chain in the preorganization of C2
      symmetric pseudopeptides: effect on S(N)2 macrocyclization reactions.
AB  - A family of pseudopeptidic macrocycles containing non-natural amino acids have
      been synthesized. The macrocyclization reaction has been studied experimentally
      and computationally, demonstrating the key role of both the amino acid side chain
      and the catalytic bromide anion. The bromide anion acts as an external template
      assisting the folding of the open-chain precursor in a proper conformation.
      Computations revealed that in the presence of the anion, the effect of the side
      chain on the energy barrier for the macrocyclization is very small. However, the
      effect on the conformational equilibria of the open-chain precursors is very
      important. Overall, the stabilization of those conformation(s) in which the two
      reactive ends of the open-chain intermediate are located at short distances from
      each other with the correct orientation is the critical parameter defining the
      success of the macrocyclization. The best yield was found for the compound
      containing cyclohexylalanine, for which the computationally-predicted most stable
      conformer in the presence of Br(-) has a proper preorganization for cyclization.
      The remarkable agreement obtained between experiments and theory reveals that the
      computational approach here considered can be of great utility for the prediction
      of the behavior of other related systems and for the design of appropriate
      synthetic routes to new macrocyclic compounds. 

PMID- 24328150
TI  - 1-Phenyl-3-(pyrid-2-yl)benzo[e][1,2,4]triazinyl: the first "Blatter radical" for
      coordination chemistry.
AB  - A neutral air- and moisture-stable N,N'-chelating radical ligand, 1-phenyl-3
      (pyrid-2-yl)benzo[e][1,2,4]triazinyl (1) was synthesized and characterized by
      electron paramagnetic resonance spectroscopy, X-ray crystallography, and magnetic
      measurements. Subsequent reaction of 1 with Cu(hfac)2.2H2O (hfac =
      hexafluoroacetylacetonate) under ambient conditions afforded the coordination
      complex Cu(1)(hfac)2 in which the radical binds to the metal in a bidentate
      fashion. Magnetic susceptibility data collected from 1.8 to 300 K indicate a
      strong ferromagnetic metal-radical interaction in the complex and weak
      antiferromagnetic radical...radical interactions between the Cu(1)(hfac)2 units.
      Detailed computational investigations support this assignment. Radical 1 is a new
      addition to the growing library of 1,2,4-triazinyl radicals and the first member
      of this family of paramagnetic species synthesized specifically for coordination
      purposes. 

PMID- 24328148
TI  - Discrimination between adenocarcinoma and normal pancreatic ductal fluid by
      proteomic and glycomic analysis.
AB  - Sensitive and specific biomarkers for pancreatic cancer are currently
      unavailable. The high mortality associated with adenocarcinoma of the pancreatic
      epithelium justifies the broadest possible search for new biomarkers that can
      facilitate early detection or monitor treatment efficacy. Protein glycosylation
      is altered in many cancers, leading many to propose that glycoproteomic changes
      may provide suitable biomarkers. In order to assess this possibility for
      pancreatic cancer, we have performed an in-depth LC-MS/MS analysis of the
      proteome and MS(n)-based characterization of the N-linked glycome of a small set
      of pancreatic ductal fluid obtained from normal, pancreatitis, intraductal
      papillary mucinous neoplasm (IPMN), and pancreatic adenocarcinoma patients. Our
      results identify a set of seven proteins that were consistently increased in
      cancer ductal fluid compared to normal (AMYP, PRSS1, GP2-1, CCDC132, REG1A,
      REG1B, and REG3A) and one protein that was consistently decreased (LIPR2). These
      proteins are all directly or indirectly associated with the secretory pathway in
      normal pancreatic cells. Validation of these changes in abundance by Western
      blotting revealed increased REG protein glycoform diversity in cancer.
      Characterization of the total N-linked glycome of normal, IPMN, and
      adenocarcinoma ductal fluid clustered samples into three discrete groups based on
      the prevalence of six dominant glycans. Within each group, the profiles of less
      prevalent glycans were able to distinguish normal from cancer on this small set
      of samples. Our results emphasize that individual variation in protein
      glycosylation must be considered when assessing the value of a glycoproteomic
      marker, but also indicate that glycosylation diversity across human subjects can
      be reduced to simpler clusters of individuals whose N-linked glycans share
      structural features. 

PMID- 24328152
TI  - Effect of addition of olive leaves before fruits extraction process to some
      monovarietal Tunisian extra-virgin olive oils using chemometric analysis.
AB  - The analysis of the effect of cultivar and olive leaves addition before the
      extraction on the different analytical values revealed significant differences (p
      < 0.05) in some parameters, mainly in peroxide value, phenols and tocopherol
      contents, and oxidative stability. Aroma profiles were also influenced by the
      different varieties and the addition of different amounts (0% and 3%) of olive
      leaves. Twenty-three compounds were characterized, representing 86.1-99.2% of the
      total volatiles. Chetoui cultivar has the highest amount of (E)-2-hexenal,
      followed by Chemlali cultivar, whereas (E)-2-hexen-1-ol was the major constituent
      of Zalmati and crossbreeding Chemlali by Zalmati cultivars. Sensory analysis
      showed that Chemlali and Chetoui Zarzis possessed a high fruity, bitter, and
      pungent taste, whereas the Zalmati and crossbreeding Chemlali by Zalmati had a
      'green' taste among its attributes. Indeed, the taste panel found an improvement
      of the oil quality when an amount of olive leaves (3%) added to the olives
      fruits. 

PMID- 24328151
TI  - Regulation of crosstalk between epithelial to mesenchymal transition molecules
      and MMP-9 mediates the antimetastatic activity of anethole in DU145 prostate
      cancer cells.
AB  - The underlying antimetastatic mechanism of anethole (1) still remains unclear in
      association with the molecules of the epithelial to mesenchymal transition (EMT).
      Herein, the role of the EMT molecules was elucidated in terms of the
      antimetastatic activity of 1 using DU145 cells. Anethole significantly inhibited
      the adhesion of DU145 cells to vitronectin-coated plates, as well as migration in
      a wound-healing assay and invasion using a Boyden chamber. Also, anethole
      suppressed the expression of MMP-9 in DU145 cells by zymography, ELISA, and RT
      PCR. Consistently, the silencing of MMP-9 enhanced the activity of 1 to
      upregulate the expression of E-cadherin and to attenuate the expression of
      Vimentin in DU145 cells. Compound 1 enhanced E-cadherin, which is an epithelial
      marker and attenuated the expression of Vimentin, Twist, and Snail as mesenchymal
      molecules at the mRNA level. Consistently, anethole upregulated E-cadherin and
      downregulated the expression of Vimentin, Twist and PI3K, and AKT at the protein
      level in DU145 cells. Conversely, the antimetastatic effects of 1 to inhibit
      invasion and the expression of MMP-9 and upregulate E-cadherin were reversed by
      the EMT inducer TGF-beta in DU145 cells. Overall, the present findings suggest
      that anethole exerts antimetastatic activity via regulation of crosstalk between
      EMT molecules and MMP-9 on the basis of the in vitro data obtained. 

PMID- 24328153
TI  - Second-order many-body perturbation theory: an eternal frontier.
AB  - Second-order many-body perturbation theory [MBPT(2)] is the lowest-ranked member
      of a systematic series of approximations convergent at the exact solutions of the
      Schrodinger equations. It has served and continues to serve as the testing ground
      for new approximations, algorithms, and even theories. This article introduces
      this basic theory from a variety of viewpoints including the Rayleigh-Schrodinger
      perturbation theory, the many-body Green's function theory based on the Dyson
      equation, and the related Feynman-Goldstone diagrams. It also explains the
      important properties of MBPT(2) such as size consistency, its ability to describe
      dispersion interactions, and divergence in metals. On this basis, this article
      surveys three major advances made recently by the authors to this theory. They
      are a finite-temperature extension of MBPT(2) and the resolution of the Kohn
      Luttinger conundrum, a stochastic evaluation of the correlation and self-energies
      of MBPT(2) using the Monte Carlo integration of their Laplace-transformed
      expressions, and an extension to anharmonic vibrational zero-point energies and
      transition frequencies based on the Dyson equation. 

PMID- 24328154
TI  - Global and targeted metabolomics reveal that Bupleurotoxin, a toxic type of
      polyacetylene, induces cerebral lesion by inhibiting GABA receptor in mice.
AB  - Polyacetylenes are widely distributed in food plants and medicinal herbs, which
      have been shown to have highly neurotoxic effects. However, there were
      insufficient studies on the toxicity of these compounds. Thus, a series of
      experiments was designed to elucidate the toxicity mechanism of bupleurotoxin
      (BETX) as a representative polyacetylene. First, male BALB/c mice were
      intragastrically administered 2.5 mg/kg of bodyweight BETX once a day for seven
      consecutive days. The histopathological results showed that BETX could induce
      severe morphological damages in the brain hippocampus. We then used metabolomics
      approaches to screen serum samples from the control and BETX-treated groups. The
      global metabolomics results revealed 17 metabolites that were perturbed after
      BETX treatment. Four of these metabolites were then verified by targeted
      metabolomics. Bioinformatics analysis with the Ingenuity Pathway Analysis (IPA)
      software found a strong correlation between the GABA receptor signaling pathway
      and these metabolites. On the basis of these results, a validation test using a
      rat hippocampal neuron cell line was performed, and the results confirmed that
      BETX inhibited GABA-induced currents (IGABA) in a competitive manner. In summary,
      our study illustrated the molecular mechanism of the toxicity of polyacetylenes.
      In addition, our study was instructive for the study of other toxic medical
      herbs. 

PMID- 24328156
TI  - Elemental characterization of PM2.5 and PM10 emitted from light duty vehicles in
      the Washburn Tunnel of Houston, Texas: release of rhodium, palladium, and
      platinum.
AB  - We report the elemental composition, including Rh, Pd, and Pt, of total (i.e.,
      tailpipe and nontailpipe) PM2.5 and PM10 emissions from predominantly gasoline
      driven light-duty vehicles (LDVs) traversing the Washburn Tunnel in Houston,
      Texas during November and December, 2012. Using a novel sample preparation and
      dynamic reaction cell-quadrupole-inductively coupled plasma-mass spectrometry
      technique, we quantify the emission of numerous representative, transition, and
      lanthanoid elements. Two sets of time integrated PM samples were collected over 3
      4week duration both inside the tunnel as well as from the tunnel ventilation air
      supply to derive accurate LDV source profiles incorporating three platinum group
      elements (PGEs) for the first time. Average Rh, Pd, and Pt concentrations from
      the tunnel ventilation air supply were 1.5, 11.1, and 4.5pgm(-3) in PM2.5 and
      3.8, 23.1, and 15.1pgm(-3) in PM10, respectively. Rh, Pd, and Pt levels were
      elevated inside the Washburn Tunnel reaching 12.5, 91.1, and 30.1pgm(-3) in PM2.5
      and 36.3, 214, and 61.1pgm(-3) in PM10, respectively. Significantly higher
      enrichment factors of Cu, Zr, Rh, Pd, Sb, and Pt (referenced to Ti in the upper
      continental crust) inside the tunnel compared with the ventilation air supply
      suggested that they are unique elemental tracers of PM derived from gasoline
      driven LDVs. This highlights the importance of advancing methods to quantify the
      trace level PGE emissions as a technique to more accurately estimate LDVs'
      contributions to airborne PM. Using the emission profile based on PGEs and
      ambient quantification, mass balancing revealed that approximately half the fine
      PM mass in the tunnel could be attributed to tailpipe emissions, approximately
      one-quarter to road dust, with smaller contributions from brake (7%) and tire
      (3%) wear. On the other hand, PM10 mostly originated from resuspended road dust
      (~50%), with progressively lower contributions from tailpipe emissions (14%),
      brake wear (9%), and tire wear (2%). 

PMID- 24328157
TI  - Microbead-based ligase detection reaction assay using a molecular beacon probe
      for the detection of low-abundance point mutations.
AB  - A microbead-based ligase detection reaction (LDR) assay using a molecular beacon
      probe was developed for the facile and rapid detection of point mutations present
      in low copy numbers in a mixed population of wild-type DNA. Biotin-tagged
      ligation products generated in the LDR were captured on the surface of
      streptavidin-modified magnetic beads for purification and concentration. The
      resulting product-tethered microbeads were combined with a molecular beacon probe
      solution, and the suspension was directly flowed into a capillary. The microbeads
      were accumulated in a confined space within the capillary using a bar magnet. The
      packed bead sample was then scanned by a fluorescence scanning imager to detect
      the presence of any mutations. With the developed methodology, we were able to
      successfully detect one cancer mutation in a mixture of 400 wild-type templates
      (t test at 95% confidence level). Furthermore, the post-LDR processing, typically
      the most laborious and time-consuming step in LDR-based mutation detection
      assays, could be carried out much more rapidly (approximately 20 min). This was
      enabled by the simple bead and fluid manipulations involved in the present assay.

PMID- 24328155
TI  - YC-1 binding to the beta subunit of soluble guanylyl cyclase overcomes allosteric
      inhibition by the alpha subunit.
AB  - Soluble guanylate cyclase (sGC) is a heterodimeric heme protein and the primary
      nitric oxide receptor. NO binding stimulates cyclase activity, leading to
      regulation of cardiovascular physiology and making sGC an attractive target for
      drug discovery. YC-1 and related compounds stimulate sGC both independently and
      synergistically with NO and CO binding; however, where the compounds bind and how
      they work remain unknown. Using linked equilibrium binding measurements, surface
      plasmon resonance, and domain truncations in Manduca sexta and bovine sGC, we
      demonstrate that YC-1 binds near or directly to the heme-containing domain of the
      beta subunit. In the absence of CO, YC-1 binds with a Kd of 9-21 MUM, depending
      on the construct. In the presence of CO, these values decrease to 0.6-1.1 MUM.
      Pfizer compound 25 bound ~10-fold weaker than YC-1 in the absence of CO, whereas
      compound BAY 41-2272 bound particularly tightly in the presence of CO (Kd = 30-90
      nM). Additionally, we found that CO binds much more weakly to heterodimeric sGC
      proteins (Kd = 50-100 MUM) than to the isolated heme domain (Kd = 0.2 MUM for
      Manduca beta H-NOX/PAS). YC-1 greatly enhanced binding of CO to heterodimeric
      sGC, as expected (Kd ~ 1 MUM). These data indicate the alpha subunit induces a
      heme pocket conformation with a lower affinity for CO and NO. YC-1 family
      compounds bind near the heme domain, overcoming the alpha subunit effect and
      inducing a heme pocket conformation with high affinity. We propose this high
      affinity conformation is required for the full-length protein to achieve high
      catalytic activity. 

PMID- 24328158
TI  - Experimental and theoretical study on palladium-catalyzed C-P bond formation via
      direct coupling of triarylbismuths with P(O)-H compounds.
AB  - A novel and highly efficient Pd-catalyzed cross-coupling of triarylbismuths with
      a variety of P(O)-H compounds has been developed that proceeds smoothly without
      exclusion of moisture or air and provides a general and powerful tool for the
      preparation of various valuable arylphosphonates, arylphosphinates, and
      arylphosphine oxides, with high atom-economy, operational simplicity of the
      procedure, and good to high yield. The coupling reaction is the first example of
      transition-metal-catalyzed C-P bond construction using triarylbismuth compounds
      as substrates. DFT calculations reveal that C-P bond formation is the rate
      determing step. 

PMID- 24328159
TI  - Self-supported single crystalline H2Ti8O17 nanoarrays as integrated three
      dimensional anodes for lithium-ion microbatteries.
AB  - Well-ordered, one-dimensional H2Ti2O5, H2Ti8O17, TiO2-B, and anatase TiO2/TiO2-B
      nanowire arrays were innovatively designed and directly grown on current
      collectors as high performance three dimensional (3D) anodes for binder and
      carbon free lithium ion batteries (LIBs). The prepared thin nanowires exhibited a
      single crystalline phase with highly uniform morphologies, diameters ranging from
      70-80 nm, and lengths of around 15 MUm. Specifically, reversible Li insertion and
      extraction reactions around 1.6-1.8 V with initial intercalation capacities of
      326 and 271 mA h g(-1) at a cycling rate of 0.1 C (where 1 C = 335 mA g(-1)) were
      observed for H2Ti8O17 and TiO2-B nanowire arrays, respectively. Among the four
      compounds investigated, the H2Ti8O17 nanowire electrode demonstrated optimal
      cycling stability, delivering a high specific discharge capacity of 157.8 mA h g(
      1) with a coulombic efficiency of 100%, even after the 500th cycle at a current
      rate of 1 C. Furthermore, the H2Ti8O17 nanowire electrode displayed superior rate
      performance with rechargeable discharge capacities of 127.2, 111.4, 87.2, and
      73.5 mA h g(-1) at 5 C, 10 C, 20 C, and 30 C, respectively. These results present
      the potential opportunity for the development of high-performance LIBs based on
      nanostructured Ti-based anode materials in terms of high stability and high rate
      capability. 

PMID- 24328160
TI  - Unexpected secoiridoid glucosides from Manulea corymbosa.
AB  - From an extract of Manulea corymbosa were isolated four known secoiridoid
      glucosides (1-4), 10 new monoterpenoid esters of secologanol, namely,
      manuleosides A-I (5-11, 13, and 14) and dimethyl rhodanthoside A (12), and four
      new phenylpropanoid esters of carbocyclic iridoid glucosides, manucorymbosides I
      IV (15-18). Also, the caffeoyl phenylethanoid glycoside verbascoside was
      isolated. The presence of secoiridoids apparently derived from loganic acid in
      the family Scrophulariaceae is unprecedented and greatly unexpected. 

PMID- 24328161
TI  - DNA origami based visualization system for studying site-specific recombination
      events.
AB  - Site-specific recombination involves reciprocal exchange between defined DNA
      sites. The reaction initiates from the formation of a recombinase-DNA synaptic
      complex, in which two recombination sites arrange in an appropriate
      configuration. However, there is incomplete information about how the topological
      state of the substrate influences the synapsis and outcome of the reaction. Here,
      we show that Cre-mediated recombination can be regulated by controlling the
      orientation and topology of the loxP substrate in a DNA frame nanoscaffold. High
      speed atomic force microscopy analyses revealed that the loxP-containing
      substrate strands in the antiparallel orientation can be recombined only through
      formation of synaptic complexes. By tethering Holliday junction (HJ)
      intermediates to DNA frames in different connection patterns and using them as a
      starting substrate, we found that the topological state of the HJ intermediates
      dictates the outcome of the resolution. Our approach should provide a new
      platform for structural-functional studies of various DNA targeting enzymes,
      especially which require formation of synaptic complexes. 

PMID- 24328162
TI  - Fat crystal migration and aggregation and polymorphism evolution during the
      formation of granular crystals in beef tallow and palm oil.
AB  - Six rectangular block all beef tallow (BT)-based and all palm oil (PO)-based
      model shortenings prepared on a laboratory scale, denoted BTMS and POMS,
      respectively, were stored under two storage conditions, (1) constant temperatures
      (5 and 20  degrees C, respectively and (2) temperature fluctuations (5  degrees C
      for 12 h and 20  degrees C for 12 h for a cycle), to induce granular crystals.
      The fat crystal migration and aggregation, sensory evaluations, and polymorphism
      evolutions during the formation of granular crystals in the above samples were
      investigated systematically. In comparison to the constant temperature storage,
      the crystal growth and hierarchical aggregation process were more quick and the
      conversion rate of the beta-form crystal was also faster in both BTMS and POMS
      under temperature cycling storage and, concomitantly, easier to induce the
      formation of granular crystals. From the comprehensive analysis of crystal sizes
      and the sensory evaluation results, it can be concluded that the detection
      threshold for graininess ranged from 40 to 90 MUm, with the smaller size being
      perceived only at higher crystal concentrations. The possible formation mechanism
      and the realistic control approaches for granular crystals in plastic fats also
      are clarified in the present study. 

PMID- 24328163
TI  - Polar alignment of Lambda-shaped basic building units within transition metal
      oxide fluoride materials.
AB  - A series of pseudosymmetrical structures of formula K10(M2OnF11-n)3X (M = V and
      Nb, n = 2, X = (F2Cl)1/3, Br, Br4/2,I4/2; M = Mo, n = 4, X = Cl, Br4/2, I4/2)
      illustrates generation of polar structures with the use of Lambda-shaped basic
      building units (BBUs). For a compound to belong to a polar space group, dipole
      moments of individual species must be partially aligned. Incorporation of d(0)
      early transition metal polyhedral BBUs into structures is a common method to
      create polar structures, owing to the second-order Jahn-Teller distortion these
      polyhedra contain. Less attention has been spent examining how to align the polar
      moments of BBUs. To address alignment, we present a study on previously reported
      bimetallic BBUs and synthesized compounds K10(M2OnF11-n)3X. These materials
      differ in their (non)centrosymmetry despite chemical and structural similarities.
      The vanadium compounds are centrosymmetric (space groups P3m1 or C2/m) while the
      niobium and molybdenum heterotypes are noncentrosymmetric (Pmn21). The difference
      in symmetry occurs owing to the presence of linear, bimetallic BBUs or Lambda
      shaped bimetallic BBUs and related packing effects. These Lambda-shaped BBUs form
      as a consequence of the coordination environment around the bridging anion of the
      metal oxide fluoride BBUs.

PMID- 24328164
TI  - Hygroscopic particle behavior studied by interdigitated array microelectrode
      impedance sensors.
AB  - The hygroscopic behavior of soluble salts bears importance in many research
      fields including atmospheric sciences, corrosion, porous building materials, and
      pharmaceuticals. Several methods have been used to study deliquescence (solid to
      liquid) and efflorescence (liquid to solid) phase transitions of these salts. In
      this study, we measured the deliquescence and efflorescence RH values of single
      salt microparticles deposited on an interdigitated microelectrode sensor via
      electrical impedance. The salts examined were NaCl, LiCl, NaBr, KCl, and MgCl2.
      Measured values were in agreement with in situ optical microscopic observations
      and, with the exception of MgCl2, literature values. In the case of MgCl2,
      deliquescence occurred at 33% RH and 12-15% RH, with the latter range being
      previously unreported. The depressed deliquescence RH was hypothesized to be a
      result of the formation of a metastable MgCl2 hydrate. Incomplete efflorescence
      of MgCl2 was also observed after exposure to <1.5% RH for up to 22 h due to
      formation of solid shells which trapped fluid. The phenomena elucidated by these
      results provide an explanation for the anomalous water retention and uptake
      behavior of MgCl2 below 33% RH reported elsewhere in the literature. The results
      presented in this study validate the use of this method as an alternative or
      complementary method for study of bulk-phase transitions of substrate-deposited
      particles across a broad RH range. These findings also demonstrate the utility of
      this method for detection of fluid trapping which cannot be directly ascertained
      by gravimetric and line-of-sight techniques commonly used in the study of
      hygroscopic particles. 

PMID- 24328165
TI  - Structural parameters controlling the fluorescence properties of phytochromes.
AB  - Phytochromes constitute a class of photoreceptors that can be photoconverted
      between two stable states. The tetrapyrrole chromophore absorbs in the red
      spectral region and displays fluorescence maxima above 700 nm, albeit with low
      quantum yields. Because this wavelength region is particularly advantageous for
      fluorescence-based deep tissue imaging, there is a strong interest to engineer
      phytochrome variants with increased fluorescence yields. Such targeted design
      efforts would substantially benefit from a deeper understanding of those
      structural parameters that control the photophysical properties of the protein
      bound chromophore. Here we have employed resonance Raman (RR) spectroscopy and
      molecular dynamics simulations for elucidating the chromophore structural changes
      in a fluorescence-optimized mutant (iRFP) derived from the PAS-GAF domain of the
      bacteriophytochrome RpBphP2 from Rhodopseudomas palustris . Both methods
      consistently reveal the structural consequences of the amino acid substitutions
      in the vicinity of the biliverdin chromophore that may account for lowering the
      propability of nonradiative excited state decays. First, compared to the wild
      type protein, the tilt angle of the terminal ring D with respect to ring C is
      increased in iRFP, accompanied by the loss of hydrogen bond interactions of the
      ring D carbonyl function and the reduction of the number of water molecules in
      that part of the chromophore pocket. Second, the overall flexibility of the
      chromophore is significantly reduced, particularly in the region of rings D and
      A, thereby reducing the conformational heterogeneity of the methine bridge
      between rings A and B and the ring A carbonyl group, as concluded from the RR
      spectra of the wild-type proteins. 

PMID- 24328166
TI  - Comparison of particle mass and solid particle number (SPN) emissions from a
      heavy-duty diesel vehicle under on-road driving conditions and a standard testing
      cycle.
AB  - It is important to understand the differences between emissions from standard
      laboratory testing cycles and those from actual on-road driving conditions,
      especially for solid particle number (SPN) emissions now being regulated in
      Europe. This study compared particle mass and SPN emissions from a heavy-duty
      diesel vehicle operating over the urban dynamometer driving schedule (UDDS) and
      actual on-road driving conditions. Particle mass emissions were calculated using
      the integrated particle size distribution (IPSD) method and called MIPSD. The
      MIPSD emissions for the UDDS and on-road tests were more than 6 times lower than
      the U.S. 2007 heavy-duty particulate matter (PM) mass standard. The MIPSD
      emissions for the UDDS fell between those for the on-road uphill and downhill
      driving. SPN and MIPSD measurements were dominated by nucleation particles for
      the UDDS and uphill driving and by accumulation mode particles for cruise and
      downhill driving. The SPN emissions were ~ 3 times lower than the Euro 6 heavy
      duty SPN limit for the UDDS and downhill driving and ~ 4-5 times higher than the
      Euro 6 SPN limit for the more aggressive uphill driving; however, it is likely
      that most of the "solid" particles measured under these conditions were
      associated with a combination release of stored sulfates and enhanced sulfate
      formation associated with high exhaust temperatures, leading to growth of
      volatile particles into the solid particle counting range above 23 nm. Except for
      these conditions, a linear relationship was found between SPN and accumulation
      mode MIPSD. The coefficient of variation (COV) of SPN emissions of particles >23
      nm ranged from 8 to 26% for the UDDS and on-road tests.

PMID- 24328167
TI  - NH4HF2 as a selective TBS-removal reagent for the synthesis of highly
      functionalized spiroketal via tandem deprotection/spiroketalization procedure.
AB  - NH4HF2 has been used for the first time to selectively remove the TBS protecting
      groups from diol ketone precursors in the synthesis of highly functionalized
      spiroketals. This method allows the synthesis of [5,6], [6,6], and [6,7]
      spiroketal skeletons, as well as benzannulated spiroketal with retention of acid
      sensitive groups. In this way, spiroketals can be synthesized with diverse
      substituent groups in the skeleton or on side chains. To demonstrate the utility
      of this methodology, the diverse transformations of highly functionalized
      spiroketal 3f were also investigated. 

PMID- 24328169
TI  - Systemic acquired resistance (50 years after discovery): moving from the lab to
      the field.
AB  - Induction of plant defense(s) against pathogen challenge(s) has been the object
      of progressively more intense research in the past two decades. Insights on
      mechanisms of systemic acquired resistance (SAR) and similar, alternative
      processes, as well as on problems encountered on moving to their practical
      application in open field, have been carefully pursued and, as far as possible,
      defined. In reviewing the number of research works published in metabolomic,
      genetic, biochemical, and crop protection correlated disciplines, the following
      outline has been adopted: 1, introduction to the processes currently considered
      as models of the innate immunity; 2, primary signals, such as salicylic acid
      (SA), jasmonic acid (JA), and abscisic acid (ABA), involved with different roles
      in the above-mentioned processes; 3, long-distance signals, identified from
      petiole exudates as mobile signaling metabolites during expressed resistance; 4,
      exogenous inducers, including the most significant chemicals known to stimulate
      the plant resistance induction and originated from both synthetic and natural
      sources; 5, fungicides shown to act as stimulators of SAR in addition to their
      biocidal action; 6, elusive mechanism of priming, reporting on the most recent
      working hypotheses on the pretranscriptional ways through which treated plants
      may express resistance upon pathogen attack and how this resistance can be
      transmitted to the next generation; 7, fitness costs and benefits of SAR so far
      reported from field application of induced resistance; 8, factors affecting
      efficacy of induced resistance in the open field, indicating that forces,
      unrevealed under controlled conditions, may be operative in the field; 9,
      concluding remarks address the efforts required to apply the strategy of crop
      resistance induction according to the rules of integrated pest management. 

PMID- 24328170
TI  - A self-organizing chemical assembly line.
AB  - Chemical syntheses generally involve a series of discrete transformations whereby
      a simple set of starting materials are progressively rendered more complex. In
      contrast, living systems accomplish their syntheses within complex chemical
      mixtures, wherein the self-organization of biomolecules allows them to form
      "assembly lines" that transform simple starting materials into more complex
      products. Here we demonstrate the functioning of an abiological chemical system
      whose simple parts self-organize into a complex system capable of directing the
      multistep transformation of the small molecules furan, dioxygen, and nitromethane
      into a more complex and information-rich product. The novel use of a self
      assembling container molecule to catalytically transform a high-energy
      intermediate is central to the system's functioning. 

PMID- 24328168
TI  - Cell-free protein synthesis from a release factor 1 deficient Escherichia coli
      activates efficient and multiple site-specific nonstandard amino acid
      incorporation.
AB  - Site-specific incorporation of nonstandard amino acids (NSAAs) into proteins
      enables the creation of biopolymers, proteins, and enzymes with new chemical
      properties, new structures, and new functions. To achieve this, amber (TAG codon)
      suppression has been widely applied. However, the suppression efficiency is
      limited due to the competition with translation termination by release factor 1
      (RF1), which leads to truncated products. Recently, we constructed a genomically
      recoded Escherichia coli strain lacking RF1 where 13 occurrences of the amber
      stop codon have been reassigned to the synonymous TAA codon (rEc.E13.DeltaprfA).
      Here, we assessed and characterized cell-free protein synthesis (CFPS) in crude
      S30 cell lysates derived from this strain. We observed the synthesis of 190+/-20
      MUg/mL of modified soluble superfolder green fluorescent protein (sfGFP)
      containing a single p-propargyloxy-L-phenylalanine (pPaF) or p-acetyl-L
      phenylalanine. As compared to the parent rEc.E13 strain with RF1, this results in
      a modified sfGFP synthesis improvement of more than 250%. Beyond introducing a
      single NSAA, we further demonstrated benefits of CFPS from the RF1-deficient
      strains for incorporating pPaF at two- and five-sites per sfGFP protein. Finally,
      we compared our crude S30 extract system to the PURE translation system lacking
      RF1. We observed that our S30 extract based approach is more cost-effective and
      high yielding than the PURE translation system lacking RF1, ~1000 times on a
      milligram protein produced/$ basis. Looking forward, using RF1-deficient strains
      for extract-based CFPS will aid in the synthesis of proteins and biopolymers with
      site-specifically incorporated NSAAs.

PMID- 24328171
TI  - Functional layers for Zn(II) ion detection: from molecular design to optical
      fiber sensors.
AB  - We report on the synthesis of a novel perylene monoimide derivative that shows
      high response and selectivity for zinc ion detection. The complexation of Zn(2+)
      by the dye is followed by FD-MS, (1)H NMR, UV-vis spectroscopy, and isothermal
      titration calorimetry. Quantum chemical calculations are performed to gain
      further insight into the electronic processes responsible for the spectroscopic
      changes observed upon complexation. Finally, the perylene dye is incorporated in
      a sol-gel silica layer coated on optical fibers that are then used for Zn(2+)
      detection in aqueous solution. 

PMID- 24328172
TI  - Recovery of dilute aqueous acetone, butanol, and ethanol with immobilized
      calixarene cavities.
AB  - Macrocyclic calixarene molecules were modified with functional groups of
      different polarities at the upper rim and subsequently grafted to mesoporous
      silica supports through a single Si atom linker. The resulting materials were
      characterized by thermogravimetric analysis, UV-visible spectroscopy, nitrogen
      physisorption, and solid-state NMR spectroscopy. Materials were then used to
      separate acetone, n-butanol, and ethanol from dilute aqueous solution, as may be
      useful in the recovery of fermentation-based biofuels. For the purpose of
      modeling batch adsorption isotherms, the materials were considered to have one
      strong adsorption site per calixarene molecule and a larger number of weak
      adsorption sites on the silica surface and external to the calixarene cavity. The
      magnitude of the net free energy change of adsorption varied from approximately
      15 to 20 kJ/mol and was found to decrease as upper-rim calixarene functional
      groups became more electron-withdrawing. Adsorption appears to be driven by weak
      van der Waals interactions with the calixarene cavity and, particularly for
      butanol, minimizing contacts with solvent water. In addition to demonstrating
      potentially useful new sorbents, these materials provide some of the first
      experimental estimates of the energy of interaction between aqueous solutes and
      hydrophobic calixarenes, which have previously been inaccessible because of the
      insolubility of most nonionic calixarene species in water. 

PMID- 24328173
TI  - Development and characterization of gene silencing DNA cages.
AB  - RNA interference (RNAi) is a powerful therapeutic strategy that induces gene
      silencing by targeting disease-causing mRNA and can lead to their removal through
      degradation pathways. The potential of RNAi is especially relevant in cancer
      therapy, as it can be designed to regulate the expression of genes involved in
      all stages of tumor development (initiation, growth, and metastasis). We have
      generated gene silencing 3D DNA prisms that integrate antisense oligonucleotide
      therapeutics at 1, 2, 4, and 6 positions. Synthesis of these structures is
      readily achieved and leads to the assembly of highly monodisperse and well
      characterized structures. We have shown that antisense strands scaffolded on DNA
      cages can readily induce gene silencing in mammalian cells and maintain gene
      knockdown levels more effectively than single and double stranded controls
      through increased stability of bound antisense units. 

PMID- 24328174
TI  - In vivo fate of avidin-nucleic acid nanoassemblies as multifunctional diagnostic
      tools.
AB  - This study describes the formulation optimization and body-cell distribution and
      clearance in mice of a dually fluorescent biodegradable poly avidin nanoassembly
      based on the novel Avidin-Nucleic-Acid-Nano-ASsembly (ANANAS) platform as a
      potential advancement of classic avidin/biotin-based targeted delivery. The
      nanoformulation circulates freely in the bloodstream; it is slowly captured by
      filter organs; it is efficiently cleared within 24-48 h, and it is poorly
      immunogenic. The system displays more favorable properties than its parent
      monomeric avidin and it is a promising tool for diagnostic purposes for future
      translational aims, for which free circulation in the bloodstream, safety,
      multifunctionality and high composition definition are all necessary
      requirements. In addition, the assembly shows a time-dependent cell penetration
      capability, suggesting it may also function as a NP-dependent drug delivery tool.
      The ease of preparation together with the possibility to fine-tune the surface
      composition makes it also an ideal candidate to understand if and how
      nanoparticle composition affects its localization. 

PMID- 24328175
TI  - Intramolecular direct oxygen transfer from oxoferryl porphyrin to a sulfide bond.
AB  - A 1:1 supramolecular complex (met-hemoCD) of 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphyrinatoiron(III) (Fe(III)TPPS) with a per-O-methylated beta
      cyclodextrin dimer having a -SCH2PyCH2S- (Py = pyridin-3,5-diyl) linker (Py3CD)
      reacted rapidly with hydrogen peroxide or cumene hydroperoxide in an aqueous
      solution forming two types of hydroperoxo or alkylperoxo intermediates, ROO
      Fe(III)(OH(-))PCD and ROO-Fe(III)(Py)PCD, which underwent rapid homolysis to the
      corresponding ferryloxo species, namely, O?Fe(IV)(OH(-))PCD and O?Fe(IV)(Py)PCD,
      respectively. For the O?Fe(IV)(OH(-))PCD species, the iron-oxo oxygen facing the
      linker gradually transferred to the nearby sulfide bond on the linker, forming
      the sulfoxidized Py3CD (Py3CD-O)/Fe(II)TPPS complex, which then bound dioxygen in
      air forming an oxy-ferrous complex, O2-Fe(II)TPPS/Py3CD-O. In contrast, the
      O?Fe(IV)(Py)PCD species, in which the iron-oxo oxygen was located on the opposite
      side of the sulfide bond on the linker across the porphyrin ring, was reduced to
      the resting state (met-hemoCD) by the surroundings without any oxidation of the
      Py3CD linker. 

PMID- 24328176
TI  - Spiroketal-based diphosphine ligands in Pd-catalyzed asymmetric allylic amination
      of Morita-Baylis-Hillman adducts: exceptionally high efficiency and new
      mechanism.
AB  - Exceptionally high activity (with a TON up to 4750) of the palladium complexes of
      SKP ligand was discovered in the catalysis of asymmetric allylic amination of MBH
      adducts with aromatic amines. A comprehensive mechanistic study indicates that
      the unique structural features of the SKP ligand, with a long P...P distance in
      its solid-state structure, were favorable for allowing two P atoms to play a
      bifunctional role in the catalysis. Herein, one of the P atom forms a C-P sigma
      bond with the terminal carbon atom of allyl moiety as a Lewis base, and an
      alternative P atom coordinates to Pd atom. The cooperative action of organo- and
      organometallic catalysis discovered in the present catalytic system is most
      likely responsible for its high activity, as well as excellent regio- and
      enantioselectivities. The mechanism disclosed in the present catalytic system is
      distinct from most of the currently recognized mechanisms for Pd-catalyzed
      allylic substitutions. 

PMID- 24328177
TI  - Characterization and phylogenetic analysis of allergenic Tryp_alpha_amyl protein
      family in plants.
AB  - Most known allergenic proteins in rice ( Oryza sativa ) seed belong to the
      Tryp_alpha_amyl family (PF00234), but the sequence characterization and the
      evolution of the allergenic Tryp_alpha_amyl family members in plants have not
      been fully investigated. In this study, two specific motifs were found besides
      the common alpha-amylase inhibitors (AAI) domain from the allergenic
      Tryp_alpha_amyl family members in rice seeds (trRSAs). To understand the
      evolution and functional importance of the Tryp_alpha_amy1 family and the
      specific motifs for the allergenic one, a BLAST search identified 75 homologous
      proteins of trRSAs (trHAs) from 22 plant species including main crops such as
      rice, maize ( Zea mays ), wheat ( Triticum aestivum ), and sorghum ( Sorghum
      bicolor ) from all available sequences in the public databases. Statistical
      analysis showed that the allergenicity of trHAs is closely associated with these
      two motifs with high number of cysteine residues (p value = 0.00026), and the
      trHAs with and without the two motifs were clustered into separate clades,
      respectively. Furthermore, significant difference was observed on the secondary
      and tertiary structures of allergenic and nonallergenic trHAs. In addition,
      expression analysis showed that trHA-encoding genes of purple false brome (
      Brachypodium distachyon ), barrel medic ( Medicago truncatula ), rice, and
      sorghum are dominantly expressed in seeds. This work provides insight into the
      understanding of the properties of allergens in the Tryp_alpha_amyl family and is
      helpful for allergy therapy. 

PMID- 24328178
TI  - Identification of modified lysozyme peptides upon photo-oxidation by LC-TOF-MS.
AB  - Protein oxidation can have major implications on the quality and safety of foods,
      but the majority of methods to evaluate oxidative damage lack specificity.
      Therefore, this study aimed to identify specific markers for protein oxidation. A
      well-characterized protein, lysozyme, was modified by photo-oxidation and
      subsequently hydrolyzed prior to peptide analysis by LC-TOF-MS. A
      semiquantitative analysis of the peptides indicated that from the seven peptides
      containing sensitive amino acids, two peptides (HGLDNYR and WWCNDGR) were highly
      affected upon photo-oxidation and have the potential to serve as markers for
      protein oxidation. Site-specific modifications enabled the description of the
      degradation pathway of several lysozyme peptides but also indicated that the
      surrounding amino acids and the 3D structure of the protein have an impact on the
      induced modifications. It is therefore advisable to evaluate protein oxidation on
      the intact protein. 

PMID- 24328179
TI  - Anomalous effect of flow rate on the electrochemical behavior at a liquid|liquid
      interface under microfluidic conditions.
AB  - We have investigated the oxidation of ferrocene at a flowing organic
      solvent|aqueous electrolyte|solid electrode junction in a microfluidic setup
      using cyclic voltammetry and fluorescent laser scanning confocal microscopy. At
      low flow rates the oxidation current decreases with increasing flow, contrary to
      the Levich equation, but at higher flow rates the current increases linearly with
      the cube root of the flow rate. This behavior is explained using a simple model
      postulating a smallest effective width of the three-phase junction, which after
      fitting to the data comes to be ca. 20 MUm. The fluorescence microscopy reveals
      mixing of the two phases close to the PDMS cover, but the liquid|liquid junction
      is stable close to the glass support. This study shows the importance of the
      solid|liquid|liquid junctions for the behavior of multiphase systems under
      microfluidic conditions. 

PMID- 24328180
TI  - Label-free in-flow detection of single DNA molecules using glass nanopipettes.
AB  - With the view of enhancing the functionality of label-free single molecule
      nanopore-based detection, we have designed and developed a highly robust,
      mechanically stable, integrated nanopipette-microfluidic device which combines
      the recognized advantages of microfluidic systems and the unique
      properties/advantages of nanopipettes. Unlike more typical planar solid-state
      nanopores, which have inherent geometrical constraints, nanopipettes can be
      easily positioned at any point within a microfluidic channel. This is highly
      advantageous, especially when taking into account fluid flow properties. We show
      that we are able to detect and discriminate between DNA molecules of varying
      lengths when motivated through a microfluidic channel, upon the application of
      appropriate voltage bias across the nanopipette. The effects of applied voltage
      and volumetric flow rates have been studied to ascertain translocation event
      frequency and capture rate. Additionally, by exploiting the advantages associated
      with microfluidic systems (such as flow control and concomitant control over
      analyte concentration/presence), we show that the technology offers a new
      opportunity for single molecule detection and recognition in microfluidic
      devices. 

PMID- 24328181
TI  - Nonequilibrium H/D isotope effects from trajectory-based nonadiabatic dynamics.
AB  - Ground-state equilibrium kinetic isotope effects can be treated well in the
      framework of transition state theory, whereas excited-state nonequilibrium
      isotope effects are theoretically less explored. In this article we show for the
      first time that trajectory-based nonadiabatic dynamics simulations are able to
      reproduce experimental values for nonequilibrium H/D isotope effects in excited
      state processes. We use high-level electronic structure calculations (MS-CASPT2,
      DFT/MRCI, and TDDFT) and full-dimensional OM2/MRCI-based nonadiabatic dynamics
      simulations to study the ultrafast intramolecular excited-state proton transfer
      (ESIPT) and the subsequent deactivation of 7-(2-pyridyl)indole (7PyIn) and its
      deuterated analogue (7PyIn-D). We evaluate a total of 1367 surface-hopping
      trajectories to establish the differences in the dynamical behavior of 7PyIn and
      7PyIn-D. The computed H/D isotope effects for ESIPT and excited-state decay are
      consistent with recent experimental results from femtosecond pump-probe resonance
      enhanced multiphoton ionization spectroscopy. We also analyze the influence of
      temperature fluctuations in the initially prepared sample on the photodynamics of
      7PyIn and 7PyIn-D. 

PMID- 24328182
TI  - High-content screening assay for identification of chemicals impacting
      spontaneous activity in zebrafish embryos.
AB  - Although cell-based assays exist, rapid and cost-efficient high-content screening
      (HCS) assays within intact organisms are needed to support prioritization for
      developmental neurotoxicity testing in rodents. During zebrafish embryogenesis,
      spontaneous tail contractions occur from late-segmentation (~19 h
      postfertilization, hpf) through early pharyngula (~29 hpf) and represent the
      first sign of locomotion. Using transgenic zebrafish (fli1:egfp) that stably
      express eGFP beginning at ~14 hpf, we have developed and optimized a 384-well
      based HCS assay that quantifies spontaneous activity within single zebrafish
      embryos after exposure to test chemicals in a concentration-response format.
      Following static exposure of one embryo per well from 5 to 25 hpf, automated
      image acquisition procedures and custom analysis protocols were used to quantify
      total body area and spontaneous activity in live embryos. Survival and imaging
      success rates across control plates ranged from 87.5 to 100% and 93.3-100%,
      respectively. Using our optimized procedures, we screened 16 chemicals within the
      US EPA's ToxCast Phase-I library, and found that exposure to abamectin and
      emamectin benzoate-both potent avermectins-abolished spontaneous activity in the
      absence of gross malformations. Overall, compared to existing locomotion-based
      zebrafish assays conducted later in development, this method provides a simpler
      discovery platform for identifying potential developmental neurotoxicants. 

PMID- 24328184
TI  - Aggregation of insulin at the interface.
AB  - Insulin has so far been the most important pharmaceutical peptide for diabetes
      treatment, assisting to regulate carbohydrate and fat metabolism in patients.
      However, aggregation of insulin occurs readily in almost every biopharmaceutical
      process, ranging from production, purification, storage, transportation,
      delivery, to in vivo utilization at the terminal. As interfaces and surfaces are
      ubiquitous in each process and strongly influence physical/chemical properties of
      insulin, it is necessary and fundamentally important to investigate the
      aggregation of insulin at various interfaces, such as aqueous-solid interface,
      water-oil interface, and air-water interface. The objective of this article is to
      briefly summarize recent progress on insulin aggregation at different interfaces,
      with special focus on the air-water interface using the Langmuir monolayer
      technique. 

PMID- 24328185
TI  - Redirecting photosynthetic electron flow into light-driven synthesis of
      alternative products including high-value bioactive natural compounds.
AB  - Photosynthesis in plants, green algae, and cyanobacteria converts solar energy
      into chemical energy in the form of ATP and NADPH, both of which are used in
      primary metabolism. However, often more reducing power is generated by the
      photosystems than what is needed for primary metabolism. In this review, we
      discuss the development in the research field, focusing on how the photosystems
      can be used as synthetic biology building blocks to channel excess reducing power
      into light-driven production of alternative products. Plants synthesize a large
      number of high-value bioactive natural compounds. Some of the key enzymes
      catalyzing their biosynthesis are the cytochrome P450s situated in the
      endoplasmic reticulum. However, bioactive compounds are often synthesized in low
      quantities in the plants and are difficult to produce by chemical synthesis due
      to their often complex structures. Through a synthetic biology approach, enzymes
      with a requirement for reducing equivalents as cofactors, such as the cytochrome
      P450s, can be coupled directly to the photosynthetic energy output to obtain
      environmentally friendly production of complex chemical compounds. By relocating
      cytochrome P450s to the chloroplasts, reducing power can be diverted toward the
      reactions catalyzed by the cytochrome P450s. This provides a sustainable
      production method for high-value compounds that potentially can solve the problem
      of NADPH regeneration, which currently limits the biotechnological uses of
      cytochrome P450s. We describe the approaches that have been taken to couple
      enzymes to photosynthesis in vivo and to photosystem I in vitro and the
      challenges associated with this approach to develop new green production
      platforms. 

PMID- 24328186
TI  - Explorations of caffeic acid derivatives: total syntheses of rufescenolide,
      yunnaneic acids C and D, and studies toward yunnaneic acids A and B.
AB  - Yunnaneic acids A-D, isolated from the roots of Salvia yunnanensis , are
      hexameric (A and B) and trimeric (C and D) assemblies of caffeic acid that
      feature an array of synthetically challenging and structurally interesting
      domains. In addition to being caffeic acid oligomers, yunnaneic acids A and B are
      formally dimeric and heterodimeric adducts of yunnaneic acids C and D. Herein we
      report the first total syntheses of yunnaneic acids C and D featuring the
      formation of their bicyclo[2.2.2]octene cores in a single step from simple
      precursors via an oxidative dearomatization/Diels-Alder cascade that may have
      biogenetic relevance. In addition, exploitation of the key intermediate resulting
      from this cascade reaction has enabled rapid access to the structurally related
      caffeic acid metabolite rufescenolide through an unexpected Lewis acid-mediated
      reduction. Finally, we report the results of extensive model studies toward
      forming the dimeric yunnaneic acids A and B. These explorations indicate that the
      innate reactivities of the monomeric fragments do not favor spontaneous formation
      of the desired dimeric linkages. Consequently, enzymatic involvement may be
      required for the biosynthesis of these more complex family members. 

PMID- 24328187
TI  - Solution-state polymer assemblies influence BCS class II drug dissolution and
      supersaturation maintenance.
AB  - Spray dried dispersions (SDDs), solid dispersions of polymer excipients and
      active pharmaceuticals, are important to the field of oral drug delivery for
      improving active stability, bioavailability, and efficacy. Herein, we examine the
      influence of solution-state polymer assemblies on amorphous spray-dried
      dispersion (SDD) performance with two BCS II model drugs, phenytoin and probucol.
      These drugs were spray dried with 4 model polymer excipients consisting of
      poly(ethylene-alt-propylene) (PEP), N,N,-dimethylacrylamide (DMA), or 2
      methacrylamido glucopyranose (MAG): amphiphilic diblock ter- and copolymers, PEP
      P(DMA-grad-MAG) and PEP-PDMA, and their respective hydrophilic analogues, P(DMA
      grad-MAG) and PDMA. Selective and nonselective solvents for the hydrophilic block
      of the diblock ter- and copolymers were used to induce or repress solution-state
      assemblies prior to spray drying. Prespray dried solution-state assemblies of
      these four polymers were probed with dynamic light scattering (DLS) and showed
      differences in solution assembly size and structure (free polymer versus
      aggregates versus micelles). Solid-state structures of spray dried dispersions
      (SDDs) showed a single glass transition event implying a homogeneous mixture of
      drug/polymer. Crystallization temperatures and enthalpies indicated that the
      drugs interact mostly with the DMA-containing portions of the polymers. Scanning
      electron microscopy was used to determine SDD particle size and morphology for
      the various polymer-drug pairings. In vitro dissolution tests showed excellent
      performance for one system, spray-dried PEP-PDMA micelles with probucol.
      Dissolution structures were investigated through DLS to determine drug-polymer
      aggregates that lead to enhanced SDD performance. Forced aggregation of the
      polymer into regular micelle structures was found to be a critical factor to
      increase the dissolution rate and supersaturation maintenance of SDDs, and may be
      an attractive platform to exploit in excipient design for oral drug delivery. 

PMID- 24328189
TI  - Coffee modulates transcription factor Nrf2 and highly increases the activity of
      antioxidant enzymes in rats.
AB  - This study investigated the effect of a 28 day administration of coffee brew on
      the activity of antioxidant enzymes in rats. After this period of 2.0 mL/day
      dosages of this beverage, the activities of hepatic superoxide dismutase,
      catalase, and glutathione peroxidase increased 74.8, 59.4, and 135.2%,
      respectively, whereas the cytosolic level of Nrf2 increased 131.3%. At the same
      time, the total antioxidant capacity of the hepatic tissue increased 25.1%,
      improving the defensive status against oxidative stress. At the end of the
      experiment, the levels of biomarkers alanine transaminase and aspartate
      transaminase remained equal to the control group, and no changes were observed in
      the hepatic histoarchiteture of the animals, suggesting that the liver tissue was
      not impaired by the exposure to coffee. The changes in enzyme activities and
      antioxidant capacity were statistically significant (p < 0.05), indicating that
      coffee could be considered an important alternative against oxidative stress and
      its correlated degenerative diseases. 

PMID- 24328190
TI  - Unprecedented CO2-promoted hydrogen permeation in Ni-BaZr0.1Ce0.7Y0.1Yb0.1O(3
      delta) membrane.
AB  - Conventional Ni-BaCeO3-based membranes possess high hydrogen permeation flux but
      suffer serious flux degradation in CO2-containing atmosphere because of the
      formation of BaCO3 insulating layer. In this work, we report a novel Ni
      BaZr0.1Ce0.7Y0.1Yb0.1O(3-delta) (Ni-BZCYYb) membrane, capable of both high
      hydrogen permeation flux and stable performance in CO2-containing atmosphere at
      900  degrees C. Most importantly, the flux is found to be promoted rather than
      being diminished by CO2 normally observed for other high temperature proton
      conductors. The flux enhancement in Ni-BZCYYb membrane is attributed to the
      increase of moisture content in feed gas. When CO2 is introduced, the reverse
      water-gas shift reaction takes place generating H2O and CO. This work
      demonstrates that CO2 can be beneficial rather than detrimental for hydrogen
      permeation membranes that possess high chemical stability.

PMID- 24328191
TI  - General in vitro method to analyze the interactions of synthetic polymers with
      human antibody repertoires.
AB  - Recent reports on the hitherto underestimated antigenicity of poly(ethylene
      glycol) (PEG), which is widely used for pharmaceutical applications, highlight
      the need for efficient testing of polymer antigenicity and for a better
      understanding of its molecular origins. With this goal in mind, we have used the
      phage-display technique to screen large, recombinant antibody repertoires of
      human origin in vitro for antibodies that bind poly(vinylpyrrolidone) (PVP). PVP
      is a neutral synthetic polymer of industrial and clinical interest that is also a
      well-known model antigen in animal studies, thus allowing the comparison of in
      vitro and in vivo responses. We have identified 44 distinct antibodies that bind
      specifically to PVP. Competitive binding assays show that the PVP-antibody
      binding constant is proportional to the polymerization degree of PVP and that
      specific binding is detected down to the vinylpyrrolidone (VP) monomer level.
      Statistical analysis of anti-PVP antibody sequences identifies an amino-acid
      motif that is shared by many phage-display-selected anti-PVP antibodies that are
      similar to a previously described natural anti-PVP antibody. This suggests a role
      for this motif in specific antibody/PVP interactions. Interestingly, sequence
      analysis also suggests that only a single antibody chain containing this shared
      motif is responsible for antibody binding to PVP, as confirmed upon systematic
      deletion of either antibody chain for 90% of selected anti-PVP antibodies.
      Overall, a large number of antibodies in the human repertoires we have screened
      bind specifically to PVP through a small number of shared amino acid motifs, and
      preliminary comparison points to significant correlations between the sequences
      of phage-display-selected anti-PVP antibodies and their natural counterparts
      isolated from immunized mice in previous studies. This study pioneers the use of
      antibody phage-display to explore the antigenicity of biotechnologically relevant
      polymers. It also paves the way for a fast, cost-effective, and systematic in
      vitro analysis, thus reducing the need for animal immunization experiments.
      Moreover, identifying the encoding DNA sequence of polymer-binding antibodies via
      phage-display enables future applications of a molecular biology approach to
      protein-polymer conjugation, based on protein-antibody fusion. 

PMID- 24328192
TI  - Electrolytic manipulation of persulfate reactivity by iron electrodes for
      trichloroethylene degradation in groundwater.
AB  - Activated persulfate oxidation is an effective in situ chemical oxidation process
      for groundwater remediation. However, reactivity of persulfate is difficult to
      manipulate or control in the subsurface causing activation before reaching the
      contaminated zone and leading to a loss of chemicals. Furthermore, mobilization
      of heavy metals by the process is a potential risk. An effective approach using
      iron electrodes is thus developed to manipulate the reactivity of persulfate in
      situ for trichloroethylene (TCE) degradation in groundwater and to limit heavy
      metals mobilization. TCE degradation is quantitatively accelerated or inhibited
      by adjusting the current applied to the iron electrode, following k1 = 0.00053.Iv
      + 0.059 (-122 A/m(3) <= Iv <= 244 A/m(3)) where k1 and Iv are the pseudo first
      order rate constant (min(-1)) and volume normalized current (A/m(3)),
      respectively. Persulfate is mainly decomposed by Fe(2+) produced from the
      electrochemical and chemical corrosion of iron followed by the regeneration via
      Fe(3+) reduction on the cathode. SO4(*-) and .OH cocontribute to TCE degradation,
      but .OH contribution is more significant. Groundwater pH and oxidation-reduction
      potential can be restored to natural levels by the continuation of electrolysis
      after the disappearance of contaminants and persulfate, thus decreasing adverse
      impacts such as the mobility of heavy metals in the subsurface. 

PMID- 24328193
TI  - Bioinspired aerobic oxidation of secondary amines and nitrogen heterocycles with
      a bifunctional quinone catalyst.
AB  - Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize
      primary amines to aldehydes. The native mechanism proceeds via an iminoquinone
      intermediate that promotes high selectivity for reactions with primary amines,
      thereby constraining the scope of potential biomimetic synthetic applications.
      Here we report a novel bioinspired quinone catalyst system consisting of 1,10
      phenanthroline-5,6-dione/ZnI2 that bypasses these constraints via an abiological
      pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of
      non-native secondary amine substrates, including pharmaceutically relevant
      nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone
      toward amine oxidation and provides a source of iodide, which plays an important
      redox-mediator role to promote aerobic catalytic turnover. These findings provide
      a valuable foundation for broader development of aerobic oxidation reactions
      employing quinone-based catalysts. 

PMID- 24328194
TI  - In vitro assays predictive of telomerase inhibitory effect of G-quadruplex
      ligands in cell nuclei.
AB  - G-quadruplex-binding and telomerase-inhibiting capacities of G-quadruplex ligands
      were examined under a cell nuclei-mimicking condition including excess double
      stranded DNA (lambda DNA) and molecular crowding cosolute (PEG 200). Under the
      cell nuclei-mimicking condition, a cationic porphyrin (TMPyP4) did not bind to
      the G-quadruplex despite the high affinity (Ka = 3.6 * 10(6) M(-1)) under a
      diluted condition without lambda DNA and PEG 200. Correspondingly, TMPyP4
      inhibited telomerase activity under the diluted condition (IC50 = 1.6 MUM) but
      not under the cell nuclei-mimicking condition. In contrast, the Ka and IC50
      values of an anionic copper phthalocyanine (Cu-APC) under the diluted (2.8 *
      10(4) M(-1) and 0.86 MUM) and the cell nuclei-mimicking (2.8 * 10(4) M(-1) and
      2.1 MUM) conditions were similar. In accordance with these results, 10 MUM TMPyP4
      did not affect the proliferation of HeLa cells, while Cu-APC efficiently
      inhibited the proliferation (IC50 = 1.4 MUM). These results show that the cell
      nuclei-mimicking condition is effective to predict capacities of G-quadruplex
      ligands in the cell. In addition, the antiproliferative effect of Cu-APC on
      normal cells was smaller than that on HeLa cells, indicating that the cell nuclei
      mimicking condition is also useful to predict side effects of ligands. 

PMID- 24328195
TI  - Transformation of biocides irgarol and terbutryn in the biological wastewater
      treatment.
AB  - The biocides irgarol and terbutryn enter the wastewater treatment plant (WWTP)
      via combined sewer systems after leaching from coatings and paints of materials.
      In this study, the biotransformation of irgarol and terbutryn was examined in
      aerobic batch experiments with activated sludge taken from the nitrification zone
      of a conventional WWTP, since currently there is no information about the fate of
      irgarol and terbutryn in biological wastewater treatment. Both, irgarol and
      terbutryn were transformed into one main transformation product (TP) following
      pseudo first-order kinetics. The TPs were tentatively identified by high
      resolution mass spectrometry (HR-MS) to be irgarol sulfoxide and terbutryn
      sulfoxide. The final confirmation of the proposed chemical structures of the TPs
      was achieved by a comparison of mass spectra and nuclear magnetic resonance (NMR)
      spectra with those of authentic reference standards (e.g., synthesized). An
      analytical method for the sensitive quantification of irgarol, terbutryn and
      their TPs in environmental samples was developed based on solid phase extraction
      (SPE) and LC tandem MS detection. Irgarol sulfoxide and terbutryn sulfoxide were
      detected in the effluents (average concentrations up to 22 ng L(-1) and 65 ng L(
      1)) of all four investigated WWTPs as well as in streams and small rivers (up to
      14 ng L(-1) and 34 ng L(-1)). Luminescent bacteria inhibition test with Vibrio
      fischeri exhibited that the TPs irgarol sulfoxide and terbutryn sulfoxide feature
      a similar bacterial toxicity than the parent compounds. 

PMID- 24328196
TI  - Results of an interlaboratory comparison of analytical methods for contaminants
      of emerging concern in water.
AB  - An evaluation of existing analytical methods used to measure contaminants of
      emerging concern (CECs) was performed through an interlaboratory comparison
      involving 25 research and commercial laboratories. In total, 52 methods were used
      in the single-blind study to determine method accuracy and comparability for 22
      target compounds, including pharmaceuticals, personal care products, and steroid
      hormones, all at ng/L levels in surface and drinking water. Method biases ranged
      from <10% to well over 100% in both matrixes, suggesting that while some methods
      are accurate, others can be considerably inaccurate. In addition, the number and
      degree of outliers identified suggest a high degree of variability may be present
      between methods currently in use. Three compounds, ciprofloxacin, 4-nonylphenol
      (NP), and 4-tert-octylphenol (OP), were especially difficult to measure
      accurately. While most compounds had overall false positive rates of <=5%,
      bisphenol A, caffeine, NP, OP, and triclosan had false positive rates >15%. In
      addition, some methods reported false positives for 17beta-estradiol and 17alpha
      ethynylestradiol in unspiked drinking water and deionized water, respectively, at
      levels higher than published predicted no-effect concentrations for these
      compounds in the environment. False negative rates were also generally <5%;
      however, rates were higher for the steroid hormones and some of the more
      challenging compounds, such as ciprofloxacin. The elevated false
      positive/negative rates of some analytes emphasize the susceptibility of many
      current methods to blank contamination, misinterpretation of background
      interferences, and/or inappropriate setting of detection/quantification levels
      for analysis at low ng/L levels. The results of both comparisons were
      collectively assessed to identify parameters that resulted in the best overall
      method performance. Liquid chromatography-tandem mass spectrometry coupled with
      the calibration technique of isotope dilution were able to accurately quantify
      most compounds with an average bias of <10% for both matrixes. These findings
      suggest that this method of analysis is suitable at environmentally relevant
      levels for most of the compounds studied. This work underscores the need for
      robust, standardized analytical methods for CECs to improve data quality,
      increase comparability between studies, and help reduce false positive and false
      negative rates. 

PMID- 24328197
TI  - Photon upconverting liquids: matrix-free molecular upconversion systems
      functioning in air.
AB  - A nonvolatile, in-air functioning liquid photon upconverting system is developed.
      A rationally designed triplet sensitizer (branched alkyl chain-modified Pt(II)
      porphyrin) is homogeneously doped in energy-harvesting liquid acceptors with a
      9,10-diphenylanthracene unit. A significantly high upconversion quantum yield of
      ~28% is achieved in the solvent-free liquid state, even under aerated conditions.
      The liquid upconversion system shows a sequence of efficient triplet energy
      transfer and migration of two itinerant excited states which eventually collide
      with each other to produce a singlet excited state of the acceptor. The observed
      insusceptibility of upconversion luminescence to oxygen indicates the sealing
      ability of molten alkyl chains introduced to liquefy chromophores. The
      involvement of the energy migration process in triplet-triplet annihilation (TTA)
      provides a new perspective in designing advanced photon upconversion systems. 

PMID- 24328198
TI  - Facile preparation of monodisperse, impurity-free, and antioxidation copper
      nanoparticles on a large scale for application in conductive ink.
AB  - Monodisperse copper nanoparticles with high purity and antioxidation properties
      are synthesized quickly (only 5 min) on a large scale (multigram amounts) by a
      modified polyol process using slightly soluble Cu(OH)2 as the precursor, L
      ascorbic acid as the reductant, and PEG-2000 as the protectant. The resulting
      copper nanoparticles have a size distribution of 135 +/- 30 nm and do not suffer
      significant oxidation even after being stored for 30 days under ambient
      conditions. The copper nanoparticles can be well-dispersed in an oil-based ink,
      which can be silk-screen printed onto flexible substrates and then converted into
      conductive patterns after heat treatment. An optimal electrical resistivity of
      15.8 MUOmega cm is achieved, which is only 10 times larger than that of bulk
      copper. The synthesized copper nanoparticles could be considered as a cheap and
      effective material for printed electronics.

PMID- 24328199
TI  - Deep red phosphorescence of cyclometalated iridium complexes by o-carborane
      substitution.
AB  - Heteroleptic (C(?)N)2Ir(acac) (C(?)N = 5-MeCBbtp (5a); 4-BuCBbtp (5b); 5-BuCBbtp
      (5c); 5-(R)CBbtp = 2-(2'-benzothienyl)-5-(2-R-ortho-carboran-1-yl)-pyridinato
      C(2),N, R = Me and n-Bu; 4-BuCBbtp = 2-(2'-benzothienyl)-4-(2-n-Bu-ortho-carboran
      1-yl)-pyridinato-C(2),N, acac = acetylacetonate) complexes supported by o
      carborane substituted C(?)N-chelating ligand were prepared, and the crystal
      structures of 5a and 5b were determined by X-ray diffraction. While 5a and 5c
      exhibit a deep red phosphorescence band centered at 644 nm, which is
      substantially red-shifted compared to that of unsubstituted (btp)2Ir(acac) (6)
      (lambdaem = 612 nm), 5b is nonemissive in THF solution at room temperature. In
      contrast, all complexes are emissive at 77 K and in the solid state.
      Electrochemical and theoretical studies suggest that the carborane substitution
      leads to the lowering of both the HOMO and LUMO levels, but has higher impact on
      the LUMO stabilization than the HOMO, resulting in the reduction of the triplet
      excited state energy. In particular, the LUMO stabilization in the 4-substituted
      5b is more contributed by carborane than that in the 5-substituted 5a. The
      solution-processed electroluminescent device incorporating 5a as an emitter
      displayed deep red phosphorescence (CIE coordinate: 0.693, 0.290) with moderate
      performance (max etaEQE = 3.8%) whereas the device incorporating 5b showed poor
      performance, as well as weak luminance. 

PMID- 24328200
TI  - Methyl anthranilate and gamma-decalactone inhibit strawberry pathogen growth and
      achene Germination.
AB  - Plant volatile compounds have been shown to affect microbial growth and seed
      germination. Here two fruity volatiles found in strawberry ( Fragaria * ananassa
      ), gamma-decalactone ("peachlike" aroma) and methyl anthranilate ("grapelike"
      aroma), were tested for effects on relevant pathogens and seedling emergence.
      Significant growth reduction was observed for Botrytis cinerea , Colletotrichum
      gloeosporioides , Colletotrichum acutatum , Phomopsis obscurans , and Gnomonia
      fragariae at 1 mM gamma-decalactone or methyl anthranilate, and 5 mM gamma
      decalactone or methyl anthranilate supplemented medium resulted in complete
      cessation of fungal growth. Phytophthora cactorum was especially sensitive to 1
      mM gamma-decalactone, showing complete growth inhibition. Bacteriostatic effects
      were observed in Xanthamonas cultures. Postharvest infestations on store-bought
      strawberries were inhibited with volatile treatment. The gamma-decalactone
      volatile inhibited strawberry and Arabidopsis thaliana germination. These
      findings show that two compounds contributing to strawberry flavor may also
      contribute to shelf life and suggest that gamma-decalactone may play an
      ecological role by preventing premature germination. 

PMID- 24328201
TI  - Revised structure of cyclolithistide A, a cyclic depsipeptide from the marine
      sponge Discodermia japonica.
AB  - A cyclic peptide was isolated from the deep-sea marine sponge Discodermia
      japonica, and its NMR spectroscopic data were identical to those reported for
      cyclolithistide A, a known antifungal depsipeptide. However, the interresidue
      HMBC correlations suggested that the amino acid sequence was different from that
      of the original structure. Moreover, chiral-phase GC-MS, combined with Marfey's
      analysis, indicated that the absolute configurations of three amino acids were
      also antipodal. Here, we propose the revised structure of cyclolithistide A and
      address the configuration of the previously unassigned 4-amino-3,5
      dihydroxyhexanoic acid (Adha) moiety. 

PMID- 24328203
TI  - Comprehensive analysis of Gly-Leu-Gly-Gly-Lys peptide dication structures and
      cation-radical dissociations following electron transfer: from electron
      attachment to backbone cleavage, ion-molecule complexes, and fragment separation.
AB  - Experimental data from ion mobility measurements and electron transfer
      dissociation were combined with extensive computational analysis of ion
      structures and dissociation energetics for Gly-Leu-Gly-Gly-Lys cations and cation
      radicals. Experimental and computational collision cross sections of (GLGGK +
      2H)(2+) ions pointed to a dominant folding motif that is represented in all low
      free-energy structures. The local folding motifs were preserved in several
      fragment ions produced by electron transfer dissociation. Gradient optimizations
      of (GLGGK + 2H)(+*) cation-radicals revealed local energy minima corresponding to
      distonic zwitterionic structures as well as aminoketyl radicals. Both of these
      structural types can isomerize to low-energy tautomers that are protonated at the
      radical-containing amide group forming a new type of intermediates, -C(*)O(
      )NH2(+)- and -C(*)(OH)NH2(+)-, respectively. Extensive mapping with B3LYP, M06
      2X, and MP2(frozen core) calculations of the potential energy surface of the
      ground doublet electronic state of (GLGGK + 2H)(+*) provided transition-state and
      dissociation energies for backbone cleavages of the N-Calpha and amide C-N bonds
      leading to ion-molecule complexes. The complexes can undergo facile prototropic
      migrations that are catalyzed by the Lys ammonium group and isomerize enolimine c
      type fragments to the more stable amide tautomers. In contrast, interfragment
      hydrogen atom migrations in the complexes were found to have relatively high
      transition energies and did not compete with fragment separation. The extensive
      analysis of the intermediate and transition-state energies led to the conclusion
      that the observed dissociations cannot proceed competitively on the same
      potential energy surface. The reactive intermediates for the dissociations
      originate from distinct electronic states that are accessed by electron transfer.

PMID- 24328204
TI  - Bioreducible comb-shaped conjugates composed of secondary amine and hydroxyl
      group-containing backbones and disulfide-linked side chains with tertiary amine
      groups for facilitating gene delivery.
AB  - Comb-shaped polymeric vectors (SS-PGEADMs) consisting of ethanolamine/cystamine
      functionalized poly(glycidyl methacrylate) (SS-PGEA-NH2) backbones and
      bioreducible poly((2-dimethyl amino)ethyl methacrylate) (PDMEAMA) side chains
      were prepared by a combination of the ring-opening reaction and atom transfer
      radical polymerization (ATRP). The SS-PGEA-NH2 backbones, which were prepared via
      the ring-opening reaction of the pendant epoxide groups of poly(glycidyl
      methacrylate) with the amine moieties of ethanolamine/cystamine, possess
      plentiful flanking secondary amine and hydroxyl groups and some flanking
      disulfide bond-containing cystamine derivatives. The primary amine groups of the
      cystamine derivatives were activated to produce bromoisobutylryl-terminated SS
      PGEA (SS-PGEA-Br) as multifunctional initiators for subsequent ATRP of DMAEMA.
      The resultant disulfide-linked short PDMEAMA side chains possess pendant tertiary
      amine groups and are biocleavable. Such SS-PGEADMs can effectively condense pDNA.
      The cytotoxicity of SS-PGEADMs could be controlled by adjusting the grafting
      amount of PDMEAMA side chains. In comparison with the pristine SS-PGEA-NH2, the
      moderate introduction of PDMEAMA side chains can further enhance the gene
      transfection efficiency in different cell lines. The present approach to well
      defined comb-shaped vectors with multifunctional groups could provide a versatile
      means for tailoring the functional structures of advanced gene/drug vectors. 

PMID- 24328205
TI  - Comparison of simulated pesticide concentrations in surface drinking water with
      monitoring data: explanations for observed differences and proposals for a new
      regulatory modeling approach.
AB  - A primary component to human health risk assessments required by the U.S.
      Environmental Protection Agency in the registration of pesticides is an
      estimation of concentrations in surface drinking water predicted by environmental
      models. The assumptions used in the current regulatory modeling approach are
      designed to be "conservative", resulting in higher predicted pesticide
      concentrations than would actually occur in the environment. This paper compiles
      previously reported modeling and monitoring comparisons and shows that current
      regulatory modeling methods result in predictions that universally exceed
      observed concentrations from the upper end of their distributions. In 50% of the
      modeling/monitoring comparisons, model predictions were more than 229 times
      greater than the observations, while, in 25% of the comparisons, model
      predictions were more than 4500 times greater than the observations. The causes
      for these overpredictions are identified, followed by suggestions for alternative
      modeling approaches that would result in predictions of pesticide concentrations
      closer to those observed. 

PMID- 24328206
TI  - Effect of antibiotics on redox transformations of arsenic and diversity of
      arsenite-oxidizing bacteria in sediment microbial communities.
AB  - In the present study, we investigated the effect of antibiotics on microbial
      arsenate (As(V)) reduction and arsenite (As(III)) oxidation in sediments
      collected from a small pond and eutrophic lake. The As(V)-reducing activities
      were less susceptible to chloramphenicol in aerobic conditions than in anaerobic
      conditions. Aerobic As(V) reduction proceeded in the presence of diverse types of
      antibiotics, suggesting that As-resistant bacteria are widely antibiotic
      resistant. In contrast, some antibiotics, e.g., chloramphenicol, strongly
      inhibited aerobic As(III) oxidation. In addition, bacterial As(III) oxidase genes
      were scarcely amplified and Proteobacteria -related 16S rRNA genes drastically
      decreased in chloramphenicol-amended cultures. Erythromycin and lincomycin, which
      successfully target many Gram-positive bacteria, scarcely affected As(III)
      oxidation, although they decreased the diversity of As(III) oxidase genes. These
      results indicate that the aerobic As(III) oxidizers in the sediment cultures are
      mainly composed of Proteobacteria and are more sensitive to certain types of
      antibiotics than the aerobic As(V) reducers. Our results suggest that antibiotic
      disturbance of environmental microbial communities may affect the biogeochemical
      cycle of As. 

PMID- 24328207
TI  - Hollow MnCo2O4 submicrospheres with multilevel interiors: from mesoporous spheres
      to yolk-in-double-shell structures.
AB  - We present a general strategy to synthesize uniform MnCo2O4 submicrospheres with
      various hollow structures. By using MnCo-glycolate submicrospheres as the
      precursor with proper manipulation of ramping rates during the heating process,
      we have fabricated hollow MnCo2O4 submicrospheres with multilevel interiors,
      including mesoporous spheres, hollow spheres, yolk-shell spheres, shell-in-shell
      spheres, and yolk-in-double-shell spheres. Interestingly, when tested as anode
      materials in lithium ion batteries, the MnCo2O4 submicrospheres with a yolk-shell
      structure showed the best performance among these multilevel interior structures
      because these structures can not only supply a high contact area but also
      maintain a stable structure. 

PMID- 24328208
TI  - Spatial distribution of U.S. household carbon footprints reveals suburbanization
      undermines greenhouse gas benefits of urban population density.
AB  - Which municipalities and locations within the United States contribute the most
      to household greenhouse gas emissions, and what is the effect of population
      density and suburbanization on emissions? Using national household surveys, we
      developed econometric models of demand for energy, transportation, food, goods,
      and services that were used to derive average household carbon footprints (HCF)
      for U.S. zip codes, cities, counties, and metropolitan areas. We find
      consistently lower HCF in urban core cities (~ 40 tCO2e) and higher carbon
      footprints in outlying suburbs (~ 50 tCO2e), with a range from ~ 25 to >80 tCO2e
      in the 50 largest metropolitan areas. Population density exhibits a weak but
      positive correlation with HCF until a density threshold is met, after which
      range, mean, and standard deviation of HCF decline. While population density
      contributes to relatively low HCF in the central cities of large metropolitan
      areas, the more extensive suburbanization in these regions contributes to an
      overall net increase in HCF compared to smaller metropolitan areas. Suburbs alone
      account for ~ 50% of total U.S. HCF. Differences in the size, composition, and
      location of household carbon footprints suggest the need for tailoring of
      greenhouse gas mitigation efforts to different populations.

PMID- 24328202
TI  - Lanthanide probes for bioresponsive imaging.

PMID- 24328209
TI  - Detection of the oxygen consumption rate of migrating zebrafish by
      electrochemical equalization systems.
AB  - A novel measurement system to determine oxygen consumption rates via respiration
      in migrating Zebrafish (Danio rerio) has been developed. A signal equalization
      system was adapted to detect oxygen in a chamber with one fish, because typical
      electrochemical techniques cannot measure respiration activities for migrating
      organisms. A closed chamber was fabricated using a pipet tip attached to a Pt
      electrode, and a columnar Vycor glass tip was used as the salt bridge. Pt
      electrode, which was attached to the chamber with one zebrafish, and Ag electrode
      were immersed in 10 mM potassium iodide (KI), and both the electrodes were
      connected externally to form a galvanic cell. Pt and Ag electrodes act as the
      cathode and anode to reduce oxygen and oxidize silver, respectively, allowing the
      deposition of insoluble silver iodide (AgI). The AgI acts as the signal source
      accumulated on the Ag electrode by conversion of oxygen. The amount of AgI
      deposited on the Ag electrode was determined by cathodic stripping voltammetry.
      The presence of zebrafish or its embryo led to a decrease in the stripping
      currents generated by a 10 min conversion of oxygen to AgI. The conversion of
      oxygen to AgI is disturbed by the migration of the zebrafish and allows the
      detection of different equalized signals corresponding to respiration activity.
      The oxygen consumption rates of the zebrafish and its embryo were estimated and
      determined to be ~4.1 and 2.4 pmol.s(-1), respectively. The deposited AgI almost
      completely disappeared with a single stripping process. The signal equalization
      system provides a method to determine the respiration activities for migrating
      zebrafish and could be used to estimate environmental risk and for effective drug
      screening. 

PMID- 24328210
TI  - The tunable hydrophobic effect on electrically doped graphene.
AB  - Using molecular dynamics simulations, we study the hydrophobic effect on
      electrically doped single layer graphene. With doping levels measured in volts,
      large changes in contact angle occur for modest voltages applied to the sheet.
      The effect can be understood as a renormalization of the surface tension between
      graphene and water in the presence of an electric field generated by the dopant
      charge, an entirely collective effect termed electrowetting. Because the
      electronic density of states scales linearly in the vicinity of the Fermi energy,
      the cosine of the contact angle scales quartically with the applied voltage
      rather than quadratically, as it would for a two-dimensional metal or in multiple
      layer graphene. While electrowetting explains the phenomenon, it does not account
      for the slight asymmetry observed in the hydrophobic response between n- and p
      doping. 

PMID- 24328212
TI  - Finger probe array for topography-tolerant scanning electrochemical microscopy of
      extended samples.
AB  - Scanning electrochemical microscopy with soft microelectrode array probes has
      recently been used to enable reactivity imaging of extended areas and to
      compensate sample corrugation perpendicular to the scanning direction. Here, the
      use of a new type of microelectrode arrays is described in which each individual
      microelectrode can independently compensate corrugations of the sample surface.
      It consists of conventional Pt microelectrodes enclosed in an insulating glass
      sheath. The microelectrodes are individually fixed to a new holder system by
      magnetic forces. The concept was tested using a large 3D sample with heights up
      to 12 MUm specially prepared by inkjet printing. The microelectrodes follow the
      topography in a constant working distance independently from each other while
      exerting low pressure on the surface. 

PMID- 24328213
TI  - Why is (SiO)(4) calculated to be tetrahedral, whereas (CO)(4) is square planar? A
      molecular orbital analysis.
AB  - Qualitative molecular orbital (MO) theory predicts that square-planar
      tetrasilacyclobutanetetraone D4h-(SiO)4 should, like D4h-(CO)4, have a triplet
      ground state, and the results of the (U)CCSD(T)-F12b/cc-pVTZ-F12//(U)B3LYP/6
      311+G(2df) calculations, reported here, confirm this expectation. Calculations at
      the same level of theory find that square-planar tetrasilacyclobutanetetrathione
      D4h-(SiS)4 also has a triplet ground state. However, these ab initio calculations
      predict that (SiO)4 and (SiS)4 both have a singlet state of much lower energy,
      with a tetrahedral (Td) equilibrium geometry and six, electron-deficient, Si-Si
      bonds. In contrast, the lowest singlet state of (CO)4 and of (CS)4 is calculated
      to prefer a D4h to a Td geometry. An analysis, based on the second-order Jahn
      Teller effect, rationalizes the influence of the electronegativity difference
      between A and Y in (AY)4 on the energy difference between a D4h and Td geometry.
      This analysis predicts that (BF)4 and (BCl)4, which are isoelectronic with,
      respectively, (CO)4 and (CS)4, should both prefer a Td to a D4h equilibrium
      geometry. These qualitative predictions have been confirmed by our calculations,
      and (BCl)4 is known experimentally to have a Td equilibrium geometry. 

PMID- 24328211
TI  - Human cellular retinaldehyde-binding protein has secondary thermal 9-cis-retinal
      isomerase activity.
AB  - Cellular retinaldehyde-binding protein (CRALBP) chaperones 11-cis-retinal to
      convert opsin receptor molecules into photosensitive retinoid pigments of the
      eye. We report a thermal secondary isomerase activity of CRALBP when bound to 9
      cis-retinal. UV/vis and (1)H NMR spectroscopy were used to characterize the
      product as 9,13-dicis-retinal. The X-ray structure of the CRALBP mutant R234W:9
      cis-retinal complex at 1.9 A resolution revealed a niche in the binding pocket
      for 9-cis-aldehyde different from that reported for 11-cis-retinal. Combined
      computational, kinetic, and structural data lead us to propose an isomerization
      mechanism catalyzed by a network of buried waters. Our findings highlight a
      specific role of water molecules in both CRALBP-assisted specificity toward 9-cis
      retinal and its thermal isomerase activity yielding 9,13-dicis-retinal. Kinetic
      data from two point mutants of CRALBP support an essential role of Glu202 as the
      initial proton donor in this isomerization reaction. 

PMID- 24328214
TI  - Synthesis and characterization of collagen grafted poly(hydroxybutyrate-valerate)
      (PHBV) scaffold for loading of bovine serum albumin capped silver (Ag/BSA)
      nanoparticles in the potential use of tissue engineering application.
AB  - The objective of this study is to synthesize and characterize collagen grafted
      poly(3-hydroxylbutyrate-co-3-hydroxylvalerate) (PHBV) film for loading of BSA
      capped silver (Ag/BSA) nanoparticles. Thermal radical copolymerization and
      aminolysis methods were used to functionalize macroporous PHBV, followed by
      collagen grafting so as to formulate collagen-g-poly(hydroxyethylmethyl acrylate)
      g-poly(3-hydroxylbutyrate-co-3-hydroxylvalerate) [collagen-g-PHEMA-g-PHBV] and
      collagen-g-aminated-poly(3-hydroxylbutyrate-co-3-hydroxylvalerate) [collagen-g
      NH2-PHBV] films, respectively. Spectroscopic (FTIR, XPS), physical (SEM), and
      thermal (TGA) techniques were used to characterize the functionalized PHBV films.
      The amount of collagen present on grafted PHBV film was quantified by the
      Bradford method. The Ag/BSA nanoparticles were then loaded on collagen grafted
      and untreated PHBV films, and the nanoparticles loading were determined by atomic
      absorption spectrometry. The amount of nanoparticles loaded on collagen grafted
      PHBV film was found to be significantly greater than that on the untreated PHBV
      film. The nanoparticles loaded PHBV film can potentially serve as a scaffold to
      promote the growth of bone cells while inhibiting the bacterial growth. 

PMID- 24328217
TI  - Supramolecular interactions in PuO2Cl4(2-) and PuCl6(2-) complexes with
      protonated pyridines: synthesis, crystal structures, and Raman spectroscopy.
AB  - The synthesis, crystal structures, and Raman spectra of seven plutonium chloride
      compounds are presented. The materials are based upon Pu(VI)O2Cl4(2-) and
      Pu(IV)Cl6(2-) anions that are charge balanced by protonated pyridinium cations.
      The single crystal X-ray structures show a variety of donor-acceptor interactions
      between the plutonium perhalo anions and the cationic pyridine groups.
      Complementary Raman spectra show that these interactions can be probed through
      the symmetric vibrational mode of the plutonyl moiety. Unlike previously reported
      studies in similar uranyl(VI) systems, the facile redox chemistry of plutonium in
      aqueous solution has demonstrated the feasibility of using not only the
      An(VI)O2Cl4(2-) anion with approximate D4h symmetry but also the approximately Oh
      An(IV)Cl6(2-) anion in order to manipulate both the structure and dimensionality
      of such hybrid materials. 

PMID- 24328216
TI  - Fluorescent exendin-4 derivatives for pancreatic beta-cell analysis.
AB  - The ability to reliably identify pancreatic beta-cells would have far reaching
      implications for a greater understanding of beta-cell biology, measurement of
      beta-cell mass in diabetes, islet transplantation, and drug development. The
      glucagon-like peptide-1 receptor (GLP1R) is highly expressed on the surface of
      insulin producing pancreatic beta-cells. Using systematic modifications of the
      GLP1R ligand, exendin-4, we screened over 25 compounds and identified a palette
      of fluorescent exendin-4 with high GLP1R binding affinity. We show considerable
      differences in affinity, as well as utility of the top candidates for flow
      cytometry and microscopy of beta-cells. Some of the developed compounds should be
      particularly useful for basic and translational beta-cell research. 

PMID- 24328218
TI  - State-resolved time-dependent wave packet and quasiclassical trajectory studies
      of the adiabatic reaction S(3P) + HD on the (1(3)A") state.
AB  - Time-dependent wave packet (TDWP) and quasiclassical trajectory (QCT)
      calculations have been carried out for the reaction S(3P) + HD(X1Sigmag+) at the
      lowest 13A" state with both rotational and vibrational excitations of reactant
      HD. The calculated integral cross sections from QCT agree fairly well with the
      TDWP calculations. The reaction probability results from TDWP show that the
      reaction displays a strong tendency to the SD channel. When the reactant HD is
      vibrationally excited, both channels are promoted apparently. The vibration of
      the HD bond tends to reduce the difference of reactivity between the two
      channels. The detailed state-to-state differential cross sections (DCSs) are
      calculated. These distributions show some significant characters of the barrier
      type reactions. At the same time, the scattering width of product SD has a
      certain relationship with its rotation excitation. For the vector properties,
      P(thetar), P(r), and P(thetar,r) distributions are calculated by QCT, and the
      increased collision energy weakens the rotational polarization of the SD
      molecule.

PMID- 24328215
TI  - Biosynthesis of nitrogenase metalloclusters.

PMID- 24328219
TI  - Ion-exchange polymer nanofibers for enhanced osteogenic differentiation of stem
      cells and ectopic bone formation.
AB  - Nanofibrous scaffolds with specific modifications have shown promising potential
      for bone tissue engineering applications. In the present study, poly(ether
      sulfone) (PES) and sulfonated PES (SPES) nanofibers were fabricated via
      electrospinning. Calcium ions were then incorporated in SPES by immersion in a
      Ca(OH)2 solution. The calcium-ion-exchanged SPES (Ca-SPES), PES, and SPES
      nanofibers were characterized and then evaluated for their osteogenic capacity:
      both in vitro using stem cell culture and in vivo after subcutaneous implantation
      in mice. After 7 days of immersion in simulated body fluid, the formation of an
      apatite layer was only observed on Ca-SPES nanofibers. According to the MTT
      results, an increasing stem cell population was detected on all scaffolds during
      the period of study. Using real-time reverse transcriptase-polymerase chain
      reaction, alkaline phosphatase activity, and calcium content assays, it was
      demonstrated that the osteogenic differentiation of stem cells was higher on Ca
      SPES scaffolds in comparison with PES and SPES nanofibers. Interestingly, Ca-SPES
      scaffolds were shown to induce ectopic bone formation after 12 weeks of
      subcutaneous implantation in mice. This was confirmed by mineralization and the
      production of collagen fibers using van Kossa and Masson's trichrome staining,
      respectively. Taken together, it was demonstrated that the incorporation of
      calcium ions into the ion-exchange nanofibrous scaffolds not only gives them the
      ability to enhance osteogenic differentiation of stem cells in vitro but also to
      induce ectopic bone formation in vivo. 

PMID- 24328220
TI  - Complex dynamical aspects of organic electrolyte solutions.
AB  - Molecular dynamics of acetone-alkali metal halide (LiBr, LiI) solutions were
      investigated using depolarized Rayleigh scattering (DRS) and low-frequency Raman
      spectroscopy in the frequency range from ~0.5 to 200 cm(-1) (~20 GHz to 6 THz).
      These experiments probe fast dynamical fluctuations of the polarizability
      anisotropy at picosecond and sub-picosecond time scales that are mainly driven by
      acetone orientational dynamics. Two distinct contributions were revealed: a fast
      process (units of picosecond, ps) related to the essentially unperturbed bulk
      solvent and a slow one (tens of ps) assigned to acetone molecules forming Li(+)
      solvation shells, decelerated by the motional constraint imposed by the cation.
      The increase of LiBr and LiI concentration significantly slows down the overall
      solvent relaxation as a consequence of the increased fraction of acetone
      molecules involved in the ion solvation shells. The global retardation is larger
      in LiI than LiBr solutions consistently with viscosity trends. This is explained
      in terms of ion association (at least ion pairing) more favorably promoted by Br(
      ) than I(-), with reduced Li(+)-acetone interactions in LiBr than LiI solutions.
      Anion-induced modulation of the Li(+)...O?C contacts, largely responsible for
      electrostriction phenomena, also affects the reduced THz-Raman spectral density,
      ascribed to ultrafast librational motions of acetone molecules. Overall, these
      findings enlighten the interplay between ion-dipole and ion-ion interactions on
      the fast solvation dynamics in electrolyte solutions of a typical polar aprotic
      solvent.

PMID- 24328221
TI  - Refractive index-based detection of gradient elution liquid chromatography using
      chip-integrated microring resonator arrays.
AB  - Refractive index-based sensors offer attractive characteristics as nondestructive
      and universal detectors for liquid chromatographic separations, but a small
      dynamic range and sensitivity to minor thermal perturbations limit the utility of
      commercial RI detectors for many potential applications, especially those
      requiring the use of gradient elutions. As such, RI detectors find use almost
      exclusively in sample abundant, isocratic separations when interfaced with high
      performance liquid chromatography. Silicon photonic microring resonators are
      refractive index-sensitive optical devices that feature good sensitivity and
      tremendous dynamic range. The large dynamic range of microring resonators allows
      the sensors to function across a wide spectrum of refractive indices, such as
      that encountered when moving from an aqueous to organic mobile phase during a
      gradient elution, a key analytical advantage not supported in commercial RI
      detectors. Microrings are easily configured into sensor arrays, and chip
      integrated control microrings enable real-time corrections of thermal drift.
      Thermal controls allow for analyses at any temperature and, in the absence of
      rigorous temperature control, obviates extended detector equilibration wait
      times. Herein, proof of concept isocratic and gradient elution separations were
      performed using well-characterized model analytes (e.g., caffeine, ibuprofen) in
      both neat buffer and more complex sample matrices. These experiments demonstrate
      the ability of microring arrays to perform isocratic and gradient elutions under
      ambient conditions, avoiding two major limitations of commercial RI-based
      detectors and maintaining comparable bulk RI sensitivity. Further benefit may be
      realized in the future through selective surface functionalization to impart
      degrees of postcolumn (bio)molecular specificity at the detection phase of a
      separation. The chip-based and microscale nature of microring resonators also
      make it an attractive potential detection technology that could be integrated
      within lab-on-a-chip and microfluidic separation devices. 

PMID- 24328223
TI  - Approaches for achieving long-term accuracy and precision of delta18O and delta2H
      for waters analyzed using laser absorption spectrometers.
AB  - The measurement of delta(2)H and delta(18)O in water samples by laser absorption
      spectroscopy (LAS) are adopted increasingly in hydrologic and environmental
      studies. Although LAS instrumentation is easy to use, its incorporation into
      laboratory operations is not as easy, owing to extensive offline data
      manipulation required for outlier detection, derivation and application of
      algorithms to correct for between-sample memory, correcting for linear and
      nonlinear instrumental drift, VSMOW-SLAP scale normalization, and in maintaining
      long-term QA/QC audits. Here we propose a series of standardized water-isotope
      LAS performance tests and routine sample analysis templates, recommended
      procedural guidelines, and new data processing software (LIMS for Lasers) that
      altogether enables new and current LAS users to achieve and sustain long-term
      delta(2)H and delta(18)O accuracy and precision for these important isotopic
      assays. 

PMID- 24328224
TI  - Highly dynamic PVP-coated silver nanoparticles in aquatic environments: chemical
      and morphology change induced by oxidation of Ag(0) and reduction of Ag(+).
AB  - The fast growing and abundant use of silver nanoparticles (AgNPs) in commercial
      products alerts us to be cautious of their unknown health and environmental
      risks. Because of the inherent redox instability of silver, AgNPs are highly
      dynamic in the aquatic system, and the cycle of chemical oxidation of AgNPs to
      release Ag(+) and reconstitution to form AgNPs is expected to occur in aquatic
      environments. This study investigated how inevitable environmentally relevant
      factors like sunlight, dissolved organic matter (DOM), pH, Ca(2+)/Mg(2+), Cl(-),
      and S(2-) individually or in combination affect the chemical transformation of
      AgNPs. It was demonstrated that simulated sunlight induced the aggregation of
      AgNPs, causing particle fusion or self-assembly to form larger structures and
      aggregates. Meanwhile, AgNPs were significantly stabilized by DOM, indicating
      that AgNPs may exist as single particles and be suspended in natural water for a
      long time or delivered far distances. Dissolution (ion release) kinetics of AgNPs
      in sunlit DOM-rich water showed that dissolved Ag concentration increased
      gradually first and then suddenly decreased with external light irradiation,
      along with the regeneration of new tiny AgNPs. pH variation and addition of
      Ca(2+) and Mg(2+) within environmental levels did not affect the tendency,
      showing that this phenomenon was general in real aquatic systems. Given that a
      great number of studies have proven the toxicity of dissolved Ag (commonly
      regarded as the source of AgNP toxicity) to many aquatic organisms, our finding
      that the effect of DOM and sunlight on AgNP dissolution can regulate AgNP
      toxicity under these conditions is important. The fact that the release of Ag(+)
      and regeneration of AgNPs could both happen in sunlit DOM-rich water implies that
      previous results of toxicity studies gained by focusing on the original nature of
      AgNPs should be reconsidered and highlights the necessity to monitor the fate and
      toxicity of AgNPs under more environmentally relevant conditions. 

PMID- 24328225
TI  - Analysis of Pfizer compounds in EPA's ToxCast chemicals-assay space.
AB  - The U.S. Environmental Protection Agency (EPA) launched the ToxCast program in
      2007 with the goal of evaluating high-throughput in vitro assays to prioritize
      chemicals that need toxicity testing. Their goal was to develop predictive
      bioactivity signatures for toxic compounds using a set of in vitro assays and/or
      in silico properties. In 2009, Pfizer joined the ToxCast initiative by
      contributing 52 compounds with preclinical and clinical data for profiling across
      the multiple assay platforms available. Here, we describe the initial analysis of
      the Pfizer subset of compounds within the ToxCast chemical (n = 1814) and in
      vitro assay (n = 486) space. An analysis of the hit rate of Pfizer compounds in
      the ToxCast assay panel allowed us to focus our mining of assays potentially most
      relevant to the attrition of our compounds. We compared the bioactivity profile
      of Pfizer compounds to other compounds in the ToxCast chemical space to gain
      insights into common toxicity pathways. Additionally, we explored the similarity
      in the chemical and biological spaces between drug-like compounds and
      environmental chemicals in ToxCast and compared the in vivo profiles of a subset
      of failed pharmaceuticals having high similarity in both spaces. We found
      differences in the chemical and biological spaces of pharmaceuticals compared to
      environmental chemicals, which may question the applicability of bioactivity
      signatures developed exclusively based on the latter to drug-like compounds if
      used without prior validation with the ToxCast Phase-II chemicals. Finally, our
      analysis has allowed us to identify novel interactions for our compounds in
      particular with multiple nuclear receptors that were previously not known. This
      insight may help us to identify potential liabilities with future novel
      compounds. 

PMID- 24328222
TI  - Detection, counting, and imaging of single nanoparticles.

PMID- 24328226
TI  - Enantio- and diastereoselective synthesis of highly substituted benzazepines by a
      multicomponent strategy coupled with organocatalytic and enzymatic procedures.
AB  - Enantiomerically pure 4,5-dihydro-1H-benzo[c]azepines with three contiguous
      stereogenic centers have been assembled by convergent strategy with a good
      control of diastereoselectivity. The two steps are as follows: an asymmetric
      organocatalytic Mannich reaction performed on Boc-imines of o
      (azidomethyl)benzaldehydes, followed by a one-pot Staudinger/aza-Wittig/Ugi
      Joullie sequence. The latter reaction represents one of the first examples of
      diastereoselective Ugi three-component reaction on a seven-membered cyclic imine.
      The o-azidomethylbenzaldehydes have been synthesized employing a simple and
      efficient chemoenzymatic strategy from commercially available building blocks. 

PMID- 24328227
TI  - Electrochemical patterning and detection of DNA arrays on a two-electrode
      platform.
AB  - We report a novel method of DNA array formation that is electrochemically formed
      and addressed with a two-electrode platform. Electrochemical activation of a
      copper catalyst, patterned with one electrode, enables precise placement of
      multiple sequences of DNA onto a second electrode surface. The two-electrode
      patterning and detection platform allows for both spatial resolution of the
      patterned DNA array and optimization of detection through DNA-mediated charge
      transport with electrocatalysis. This two-electrode platform has been used to
      form arrays that enable differentiation between well-matched and mismatched
      sequences, the detection of TATA-binding protein, and sequence-selective DNA
      hybridization. 

PMID- 24328228
TI  - Strength of DNA sticky end links.
AB  - Sticky ends are unpaired nucleotides at the ends of DNA molecules that can
      associate to link DNA segments. Self-assembly of DNA molecules via sticky ends is
      currently used to grow DNA structures with desired architectures. The sticky end
      links are the weakest parts of such structures. In this work, the strength of
      sticky end links is studied by computational means. The number of basepairs in
      the sticky end and the sequence are varied, and the response to tension along the
      axis of the molecule is evaluated using a full atomistic model. It is observed
      that, generally, increasing the number of basepairs in the sticky end increases
      the strength, but the central factor controlling this parameter is the basepair
      sequence. The sticky ends are divided into two classes of low and high strength.
      The second class has strength comparable with that of a double stranded molecule
      with one nick in one of the strands. The strength of the first class is roughly
      half that of the strong sticky ends. For all strong sticky ends tested, the
      enhanced stability is associated with the formation of an unusually stable
      complex composed from two basepairs and two flanking bases of certain sequence.
      This complex rotates and aligns with the direction of the force allowing
      significant deformation and providing enhanced strength. This is similar to a
      mechanism recently suggested to enhance the mechanical stability of an RNA
      kissing loop from the Moloney murine leukemia virus. The model is tested against
      experimental structural data for sticky ends and against published simulation
      results for the stretch of double stranded DNA. The results provide guidance for
      the design of DNA self-assembled structures and indicate the types of sticky ends
      desirable if maximizing the strength and stability of these structures is
      targeted. 

PMID- 24328229
TI  - Design, synthesis, and properties of phthalocyanine complexes with main-group
      elements showing main absorption and fluorescence beyond 1000 nm.
AB  - We present a comprehensive description of the unique properties of newly
      developed phthalocyanines (Pcs) containing main-group elements that absorb and
      emit in the near-IR region. Group 16 (S, Se, and Te) elements and group 15 (P,
      As, and Sb) elements were used as peripheral and central (core) substituents.
      With the introduction of group 16 elements into free-base Pc, a red-shift of the
      Q-band was observed, as a result of the electron-donating ability of group 16
      elements particularly at the alpha positions. An X-ray crystallographic analysis
      of alpha-ArS-, ArSe-, and ArTe-linked free-base Pcs was also successfully
      performed, and the relationship between structure and optical properties was
      clarified. When a group 15 element ion was introduced into the center of the Pc
      ring, the resulting Pcs showed a single Q-band peak beyond 1000 nm (up to 1056 nm
      in CH2Cl2). In particular, [(ArS)8PcP(OMe)2](+) and [(ArS)8PcAs(OMe)2](+)
      exhibited a distinct fluorescence in the 960-1400 nm region with moderate quantum
      yields. The atomic radius of the group 15 element is important for determining
      the Pc structure, so that this can be controlled by the choice of group 15
      elements. Electrochemical data revealed, while MO calculations suggested, that
      the red-shift of the Q-band is attributable to a decrease of the HOMO-LUMO gap
      due to significant and moderate stabilization of the LUMO and HOMO, respectively.
      The effect of peripheral substutuents and a central P(V) ion on the Q-band shift
      was independently predicted by MO calculations, while the magnitude of the total
      calculated shift was in good agreement with the experimental observations. The
      combination of spectral, electrochemical, and theoretical considerations revealed
      that all of the central group 15 elements, peripheral group 16 elements, and
      their positions are necessary to shift the Q-band beyond 1000 nm, indicating that
      the substitution effects of group 15 and 16 elements act synergistically. The Pcs
      having Q-bands beyond 1000 nm in this study also had stability under aerobic
      conditions comparative to that of CuPc, which is presently being widely used in
      consumer products. 

PMID- 24328230
TI  - Tunneling above the crossover temperature.
AB  - Quantum mechanical tunneling of atoms plays a significant role in many chemical
      reactions. The crossover temperature between classical and quantum movement is a
      convenient preliminary indication of the importance of tunneling for a particular
      reaction. Here we show, using instanton theory, that quantum tunneling is
      possible significantly above this crossover temperature for specific forms of the
      potential energy surface. We demonstrate the effect on an analytic potential as
      well as a chemical system. While protons move asynchronously along a Grotthuss
      chain in the classical high-temperature range, the onset of tunneling results in
      a synchronization of their movement. 

PMID- 24328231
TI  - Microwave-assisted self-doping of TiO2 photonic crystals for efficient
      photoelectrochemical water splitting.
AB  - In this article, we report that the combination of microwave heating and ethylene
      glycol, a mild reducing agent, can induce Ti(3+) self-doping in TiO2. A
      hierarchical TiO2 nanotube array with the top layer serving as TiO2 photonic
      crystals (TiO2 NTPCs) was selected as the base photoelectrode. The self-doped
      TiO2 NTPCs demonstrated a 10-fold increase in visible-light photocurrent density
      compared to the nondoped one, and the optimized saturation photocurrent density
      under simulated AM 1.5G illumination was identified to be 2.5 mA cm(-2) at 1.23 V
      versus reversible hydrogen electrode, which is comparable to the highest values
      ever reported for TiO2-based photoelectrodes. The significant enhancement of
      photoelectrochemical performance can be ascribed to the rational coupling of
      morphological and electronic features of the self-doped TiO2 NTPCs: (1) the
      periodically morphological structure of the photonic crystal layer traps
      broadband visible light, (2) the electronic interband state induced from self
      doping of Ti(3+) can be excited in the visible-light region, and (3) the captured
      light by the photonic crystal layer is absorbed by the self-doped interbands. 

PMID- 24328232
TI  - Spontaneous prebiotic formation of a beta-ribofuranoside that self-assembles with
      a complementary heterocycle.
AB  - The RNA World hypothesis is central to many current theories regarding the origin
      and early evolution of life. However, the formation of RNA by plausible prebiotic
      reactions remains problematic. Formidable challenges include glycosidic bond
      formation between ribose and the canonical nucleobases, as well as the inability
      of nucleosides to mutually select their pairing partners from a complex mixture
      of other molecules prior to polymerization. Here we report a one-pot model
      prebiotic reaction between a pyrimidine nucleobase (2,4,6-triaminopyrimidine,
      TAP) and ribose, which produces TAP-ribose conjugates in high yield (60-90%).
      When cyanuric acid (CA), a plausible ancestral nucleobase, is mixed with a crude
      TAP+ribose reaction mixture, micrometer-length supramolecular, noncovalent
      assemblies are formed. A major product of the TAP+ribose reaction is a beta
      ribofuranoside of TAP, which we term TARC. This nucleoside is also shown to
      efficiently form supramolecular assemblies in water by pairing and stacking with
      CA. These results provide a proof-of-concept system demonstrating that several
      challenges associated with the prebiotic emergence of RNA, or pre-RNA polymers,
      may not be as problematic as widely believed. 

PMID- 24328233
TI  - Subsecond and in situ chemical speciation of Pt/Al(2)O(3) during oxidation
      reduction cycles monitored by high-energy resolution off-resonant X-ray
      spectroscopy.
AB  - We report an in situ time-resolved high-energy resolution off-resonant
      spectroscopy study with subsecond resolution providing insight into the oxidation
      and reduction steps of a Pt catalyst during CO oxidation. The study shows that
      the slow oxidation step is composed of two characteristic stages, namely,
      dissociative adsorption of oxygen followed by partial oxidation of Pt subsurface.
      By comparing the experimental spectra with theoretical calculations, we found
      that the intermediate chemisorbed O on Pt is adsorbed on atop position, which
      suggests surface poisoning by CO or surface reconstruction. 

PMID- 24328234
TI  - Carbon dioxide hydrate phase equilibrium and cage occupancy calculations using ab
      initio intermolecular potentials.
AB  - Gas hydrate deposits are receiving increased attention as potential locations for
      CO2 sequestration, with CO2 replacing the methane that is recovered as an energy
      source. In this scenario, it is very important to correctly characterize the cage
      occupancies of CO2 to correctly assess the sequestration potential as well as the
      methane recoverability. In order to predict accurate cage occupancies, the guest
      host interaction potential must be represented properly. Earlier, these potential
      parameters were obtained by fitting to experimental equilibrium data and these
      fitted parameters do not match with those obtained by second virial coefficient
      or gas viscosity data. Ab initio quantum mechanical calculations provide an
      independent means to directly obtain accurate intermolecular potentials. A
      potential energy surface (PES) between H2O and CO2 was computed at the MP2/aug-cc
      pVTZ level and corrected for basis set superposition error (BSSE), an error
      caused due to the lower basis set, by using the half counterpoise method.
      Intermolecular potentials were obtained by fitting Exponential-6 and Lennard
      Jones 6-12 models to the ab initio PES, correcting for many-body interactions. We
      denoted this model as the "VAS" model. Reference parameters for structure I
      carbon dioxide hydrate were calculated using the VAS model (site-site ab initio
      intermolecular potentials) as DeltaMU(w)(0) = 1206 +/- 2 J/mol and DeltaH(w)(0) =
      1260 +/- 12 J/mol. With these reference parameters and the VAS model, pure CO2
      hydrate equilibrium pressure was predicted with an average absolute deviation of
      less than 3.2% from the experimental data. Predictions of the small cage
      occupancy ranged from 32 to 51%, and the large cage is more than 98% occupied.
      The intermolecular potentials were also tested by calculating the pure CO2
      density and diffusion of CO2 in water using molecular dynamics simulations.

PMID- 24328235
TI  - Cerberus nanoemulsions produced by multidroplet flow-induced fusion.
AB  - Through extreme flow-induced fusion and rupturing of microscale droplets within a
      mixture of two or more oil-in-water emulsions, each having a different type of
      mutually immiscible oil, we create complex oil-in-water nanoemulsions composed of
      multicomponent compartmentalized nanodroplets. The extreme flow temporarily
      overcomes the repulsive barrier between oil droplets, arising from stabilizing
      surfactant molecules on the droplet interfaces, thereby causing multidroplet
      fusion as well as droplet fission down to the nanoscale. After the droplets leave
      the vicinity of extreme flow, they remain stable against subsequent coarsening
      and coalescence. Using this highly parallel, top-down, nonequilibrium synthetic
      approach, we create bulk quantities of engulfed-linear Cerberus oil-in-water
      nanoemulsions. Each Cerberus nanodroplet contains three different immiscible oils
      that form complex-shaped internal compartments, as revealed by cryogenic
      transmission electron microscopy (cryo-TEM). Within a given Cerberus nanodroplet,
      depending upon the interfacial tensions and relative volume fractions of the
      different oils, the internal oil-oil interfaces can be significantly deformed.
      Such multicomponent compartmentalized oil nanodroplets have the capacity of
      holding different types of oil-soluble cargo molecules, including fluorinated
      drug molecules, which have a wide variety of functional capacities and the
      potential for local synergistic effects. Their size range is small enough to
      permit a wide variety of pharmaceutical applications. As such, Cerberus
      nanoemulsions open up possibilities for simultaneously delivering several
      different types of oil-soluble drug molecules, each of which is readily soluble
      in at least one of the different types of immiscible oils, to the same cell or
      tissue. 

PMID- 24328236
TI  - Bis(imino)pyridine cobalt-catalyzed alkene isomerization-hydroboration: a
      strategy for remote hydrofunctionalization with terminal selectivity.
AB  - Bis(imino)pyridine cobalt methyl complexes are active for the catalytic
      hydroboration of terminal, geminal, disubstituted internal, tri- and
      tetrasubstituted alkenes using pinacolborane (HBPin). The most active cobalt
      catalyst was obtained by introducing a pyrrolidinyl substituent into the 4
      position of the bis(imino)pyridine chelate, enabling the facile hydroboration of
      sterically hindered substrates such as 1-methylcyclohexene, alpha-pinene, and 2,3
      dimethyl-2-butene. Notably, these hydroboration reactions proceed with high
      activity and anti-Markovnikov selectivity in neat substrates at 23  degrees C.
      With internal olefins, the cobalt catalyst places the boron substituent
      exclusively at the terminal positions of an alkyl chain, providing a convenient
      method for hydrofunctionalization of remote C-H bonds. 

PMID- 24328237
TI  - Effects of chloride and ionic strength on physical morphology, dissolution, and
      bacterial toxicity of silver nanoparticles.
AB  - In this study, we comprehensively evaluate chloride- and ionic-strength-mediated
      changes in the physical morphology, dissolution, and bacterial toxicity of silver
      nanoparticles (AgNPs), which are one of the most-used nanomaterials. The findings
      isolate the impact of ionic strength from that of chloride concentration. As
      ionic strength increases, AgNP aggregation likewise increases (such that the
      hydrodynamic radius [HR] increases), fractal dimension (Df) strongly decreases
      (providing increased available surface relative to suspensions with higher Df),
      and the release of Ag(aq) increases. With increased Ag(+) in solution,
      Escherichia coli demonstrates reduced tolerance to AgNP exposure (i.e., toxicity
      increases) under higher ionic strength conditions. As chloride concentration
      increases, aggregates are formed (HR increases) but are dominated by AgCl(0)(s)
      bridging of AgNPs; relatedly, Df increases. Furthermore, AgNP dissolution
      strongly increases under increased chloride conditions, but the dominant,
      theoretical, equilibrium aqueous silver species shift to negatively charged
      AgClx((x-1)-) species, which appear to be less toxic to E. coli. Thus, E. coli
      demonstrates increased tolerance to AgNP exposure under higher chloride
      conditions (i.e., toxicity decreases). Expression measurements of katE, a gene
      involved in catalase production to alleviate oxidative stress, support oxidative
      stress in E. coli as a result of Ag(+) exposure. Overall, our work indicates that
      the environmental impacts of AgNPs must be evaluated under relevant water
      chemistry conditions. 

PMID- 24328238
TI  - Amplified detection of T4 polynucleotide kinase activity by the coupled lambda
      exonuclease cleavage reaction and catalytic assembly of bimolecular beacons.
AB  - The phosphorylation of nucleic acid catalyzed by polynucleotide kinase is an
      indispensible procedure involved in many vital cellular activities such as DNA
      recombination and DNA repair. Herein, a novel strategy for the sensitive
      determination of T4 polynucleotide kinase (PNK) activity and inhibition was
      proposed, which combined exonuclease enzyme reaction and bimolecular beacons (bi
      MBs)-based signal amplification. A hairpin probe (HP) with 5'-hydroxyl termini
      and two different types of molecular beacons (MBs), MB1 and MB2, is designed.
      Taking advantage of the efficient enzyme reactions, namely the phosphorylation of
      HP by PNK and the lambda exonuclease cleavage reaction, the trigger DNA fragment
      can be released from HP and is used to trigger the catalytic assembly of
      bimolecular beacons, resulting in a remarkably amplified fluorescence signal
      toward PNK activity detection. The detection limit of this method toward PNK was
      obtained as 1 mU/mL, which was superior or comparable with the reported methods.
      Furthermore, the facile and sensitive method can also be used to screen the
      inhibition effects toward several common inhibitors. It provides a promising
      platform for sensitive determination of nucleotide kinase activity and
      inhibition, and also shows great potential for biological process research, drug
      discovery, and clinic diagnostics. 

PMID- 24328239
TI  - Cyclization reactions of anode-generated amidyl radicals.
AB  - Amidyl radicals have been generated from amides under mild conditions electro
      oxidatively. Their reactivity toward electron-rich double bonds to form five- and
      six-membered rings has been demonstrated experimentally and explored with density
      functional theory (DFT) calculations (UB3LYP/6-31G(d,p)). 

PMID- 24328240
TI  - Chain or ring: which one is favorable in nitrogen-rich molecules N6XHm, N8XHm,
      and N10XHm (X = B, Al, Ga, m = 1 and X = C, Si, Ge, m = 2)?
AB  - A series of nitrogen-rich molecules N6XHm, N8XHm, and N10XHm (X = B, Al, Ga, m =
      1 and X = C, Si, Ge, m = 2) consisting of N3 and N5 radicals, are systematically
      investigated by using B3LYP and B3PW91 DFT methods. It is found that for the
      nitrogen-rich molecules, the structures with N3-chains (N5-ring) are more stable
      than those containing a N3-ring (N5-chain). This result could be well-explained
      by the intrinsic stability of the N3 and N5 radicals and their charge
      distribution in nitrogen-rich molecules. The dissociation energies further
      indicate that the B-doped and C-doped structures are the most stable among the
      molecules with three elements of group 13 and 14, respectively. Energy
      decomposition analysis shows the bond of boron-nitrogen is stronger than that of
      carbon-nitrogen. Detailed bonding analysis demonstrates that the B-N bond is
      determined by sigma and pi interactions between the B and N atoms, whereas C-N
      bonds by only sigma interactions. These results imply that the boron atom is more
      suitable than the carbon atom for building the nitrogen-rich molecules studied in
      this article. 

PMID- 24328241
TI  - Removal of phosphate from eutrophic lakes through adsorption by in situ formation
      of magnesium hydroxide from diatomite.
AB  - Since in situ formation of Mg(OH)2 can efficiently sorb phosphate (PO4) from low
      concentrations in the environment, a novel dispersed magnesium oxide nanoflake
      modified diatomite adsorbent (MOD) was developed for use in restoration of
      eutrophic lakes by removal of excess PO4. Various adsorption conditions, such as
      pH, temperature and contact time were investigated. Overall, sorption capacities
      increased with increasing temperature and contact time, and decreased with
      increasing pH. Adsorption of PO4 was well described by both the Langmuir isotherm
      and pseudo second-order models. Theoretical maximum sorption capacity of MOD for
      PO4 was 44.44-52.08 mg/g at experimental conditions. Characterization of PO4
      adsorbed to MOD by use of X-ray powder diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS) and solid state (31)P nuclear magnetic resonance revealed that
      electrostatic attraction, surface complexation and chemical conversion in situ
      were the major forces in adsorption of PO4. Mg(OH)2 formed in situ had a net
      positive charge on the surface of the MOD that could adsorb PO4(3-) and HPO4(2-)
      anion to form surface complex and gradually convert to Mg3(PO4)2 and MgHPO4.
      Efficiency of removal of PO4 was 90% when 300 mg MOD/L was added to eutrophic
      lake water. Results presented here demonstrated the potential use of the MOD for
      restoration of eutrophic lakes by removal of excess PO4. 

PMID- 24328242
TI  - Regioisomer-dependent endo- and exocyclic coordination of bis-dithiamacrocycles.
AB  - Syntheses of the regioisomers of bis-dithiamacrocycle and the regioisomer
      controlled endo- and exocyclic coordination behaviors are reported. Direct bis
      cyclization reaction of 1,2,4,5-tetra(bromomethyl)benzene with 3,6-dioxa-1,8
      octanedithiol led to a mixture of two bis-dithiamacrocycle regioisomers (ortho
      type; o-bis-L and meta-type; m-bis-L) which were separated by recrystallization
      and column chromatography. When the two isomers were reacted with AgPF6, o-bis-L
      gave an endocyclic one-dimensional (1-D) coordination polymer {[Ag3(o-bis
      L)2(CH3CN)](PF6)3.2CH3CN}n (1) with a 3:2 (metal-to-ligand) stoichiometry, while
      m-bis-L afforded an exocoordination-based 1-D polymeric complex {[Ag(m-bis
      L)](PF6)}n (2) with a 2:2 stoichiometry. The observed endo- and exocoordination
      modes depending on the isomers were discussed in terms of the S...S distances in
      the bis-dithiamacrocycle isomers. Due to the closer S...S distance in each
      macrocyclic ring, o-bis-L is suitable for the endocoordination. However, m-bis-L
      forms an exocyclic complex because the S...S distance between two macrocyclic
      rings is shorter than that in one macrocyclic ring. NMR experiments also revealed
      that o-bis-L and m-bis-L form the endo- and the exocyclic complexes,
      respectively, in solution. 

PMID- 24328243
TI  - FT-IR spectroscopy and density functional theory calculations of 13C
      isotopologues of the helical peptide Z-Aib6-OtBu.
AB  - Isotope-edited FT-IR spectroscopy is a combined synthetic and spectroscopic
      method used to characterize local (e.g., residue-level) vibrational environments
      of biomolecules. We have prepared the 3(10) helical peptide Z-Aib6-OtBu and seven
      (13)C-enriched analogues that vary only in the number and position(s) of (13)C?O
      isotopic enrichment. FT-IR spectra of these eight peptides solvated in the
      nonpolar aprotic solvent dichloromethane have been collected and compared to
      frequency, intensity, and normal mode results of DFT calculations. Single (13)C
      enrichment of amide functional groups tends to localize amide I vibrational
      eigenmodes, providing residue-specific information regarding the local
      environment (e.g., hydrogen bonding or solvent exposure) of the peptide bond.
      Double (13)C enrichment of Z-Aib6-OtBu allows for examination of interamide
      coupling between two labeled amide functional groups, providing experimental
      evidence of interamide coupling in the context of 3(10) helical structure.
      Although the calculated and observed interamide couplings of Z-Aib6-OtBu are a
      few cm(-1) and less, the eight peptides exhibit distinct infrared spectra,
      revealing details of interamide coupling and residue level vibrational
      environments.

PMID- 24328244
TI  - Novel architecture of plasmon excitation based on self-assembled nanoparticle
      arrays for photovoltaics.
AB  - An efficient approach to producing hexagonally self-assembled and well-dispersed
      gold (Au) nanoparticles (NPs) in the pores of porous anodic aluminum oxide (AAO)
      is reported. This approach is particularly useful for tuning the surface plasmon
      resonance frequency of Au NPs by varying the effective dielectric constant of
      AAO. A strongly enhanced Raman spectrum of dye molecule rhodamine 6G using these
      well-dispersed Au NPs revealed that such a self-assembled Au NP array can induce
      a strong plasmonic field. Furthermore, we demonstrated a new architecture of
      plasmon excitation in a bulk heterojunction (BHJ) inverted organic solar cell
      (IOSC) using the Au NP array with AAO. The optical response of an active layer
      poly(3-hexylthiophene):(6,6)-phenyl-C61-butyric acid methyl ester was enhanced by
      this strong plasmonic field associated a well-dispersed Au NP array. A
      comparative study of AAO with and without Au NPs confirmed plasmonic improvement
      of the BHJ IOSC. Simulation results showed that Au NPs concentrate the incoming
      light into a strongly localized field and enhance light absorption in a wide
      wavelength range. 

PMID- 24328245
TI  - Managing critical materials with a technology-specific stocks and flows model.
AB  - The transition to low carbon infrastructure systems required to meet climate
      change mitigation targets will involve an unprecedented roll-out of technologies
      reliant upon materials not previously widespread in infrastructure. Many of these
      materials (including lithium and rare earth metals) are at risk of supply
      disruption. To ensure the future sustainability and resilience of infrastructure,
      circular economy policies must be crafted to manage these critical materials
      effectively. These policies can only be effective if supported by an
      understanding of the material demands of infrastructure transition and what reuse
      and recycling options are possible given the future availability of end-of-life
      stocks. This Article presents a novel, enhanced stocks and flows model for the
      dynamic assessment of material demands resulting from infrastructure transitions.
      By including a hierarchical, nested description of infrastructure technologies,
      their components, and the materials they contain, this model can be used to
      quantify the effectiveness of recovery at both a technology remanufacturing and
      reuse level and a material recycling level. The model's potential is demonstrated
      on a case study on the roll-out of electric vehicles in the UK forecast by UK
      Department of Energy and Climate Change scenarios. The results suggest policy
      action should be taken to ensure Li-ion battery recycling infrastructure is in
      place by 2025 and NdFeB motor magnets should be designed for reuse. This could
      result in a reduction in primary demand for lithium of 40% and neodymium of 70%. 

PMID- 24328246
TI  - Structural characterization of the thermally tolerant pectin methylesterase
      purified from citrus sinensis fruit and its gene sequence.
AB  - Despite the longstanding importance of the thermally tolerant pectin
      methylesterase (TT-PME) activity in citrus juice processing and product quality,
      the unequivocal identification of the protein and its corresponding gene has
      remained elusive. TT-PME was purified from sweet orange [ Citrus sinensis (L.)
      Osbeck] finisher pulp (8.0 mg/1.3 kg tissue) with an improved purification scheme
      that provided 20-fold increased enzyme yield over previous results. Structural
      characterization of electrophoretically pure TT-PME by MALDI-TOF MS determined
      molecular masses of approximately 47900 and 53000 Da for two principal
      glycoisoforms. De novo sequences generated from tryptic peptides by MALDI-TOF/TOF
      MS matched multiple anonymous Citrus EST cDNA accessions. The complete tt-pme
      cDNA (1710 base pair) was cloned from a fruit mRNA library using RT- and RLM-RACE
      PCR. Citrus TT-PME is a novel isoform that showed higher sequence identity with
      the multiply glycosylated kiwifruit PME than to previously described Citrus
      thermally labile PME isoforms. 

PMID- 24328247
TI  - Atomic structure and handedness of the building block of a biological assembly.
AB  - Noncovalent supramolecular assemblies possess in general several unique subunit
      subunit interfaces.The basic building block of such an assembly consists of
      several subunits and contains all unique interfaces. Atomic-resolution structures
      of monomeric subunits are typically accessed by crystallography or solution NMR
      and fitted into electron microscopy density maps. However, the structure of the
      intact building block in the assembled state remains unknown with this hybrid
      approach. Here, we present the solid-state NMR atomic structure of the building
      block of the type III secretion system needle. The building block structure
      consists of a homotetrameric subunit complex with three unique supramolecular
      interfaces. Side-chain positions at the interfaces were solved at atomic detail.
      The high-resolution structure reveals unambiguously the helical handedness of the
      assembly, determined to be right-handed for the type III secretion system
      needle.Additionally, the axial rise per subunit could be extracted from the
      tetramer structure and independently validated by mass-per-length measurements. 

PMID- 24328248
TI  - Effect of simulation on knowledge of advanced cardiac life support, knowledge
      retention, and confidence of nursing students in Jordan.
AB  - This study examined the effect of simulation on nursing students' knowledge of
      advanced cardiac life support (ACLS), knowledge retention, and confidence in
      applying ACLS skills. An experimental, randomized controlled (pretest-posttest)
      design was used. The experimental group (n = 40) attended an ACLS simulation
      scenario, a 4-hour PowerPoint presentation, and demonstration on a static
      manikin, whereas the control group (n = 42) attended the PowerPoint presentation
      and a demonstration only. A paired t test indicated that posttest mean knowledge
      of ACLS and confidence was higher in both groups. The experimental group showed
      higher knowledge of ACLS and higher confidence in applying ACLS, compared with
      the control group. Traditional training involving PowerPoint presentation and
      demonstration on a static manikin is an effective teaching strategy; however,
      simulation is significantly more effective than traditional training in helping
      to improve nursing students' knowledge acquisition, knowledge retention, and
      confidence about ACLS.

PMID- 24328250
TI  - Addressing the challenges of nursing student attrition.
AB  - With the passage of the Affordable Care Act and as the number of aging and
      diverse individuals in society increases, access to health care will expand and
      the need for more competent and diverse nursing graduates will increase. An
      adequate number of nurse graduates is imperative to meet societal demands;
      however, this is complicated by high nursing student attrition rates. This
      article examines the need for more nurses (including those from diverse
      backgrounds), current attrition rates among schools of nursing, at-risk student
      characteristics, and previous attempts to increase student success. Applying the
      evidence to practice, findings from a multipronged approach to increase student
      success within an associate degree nursing program located within a historically
      Black college and university in the midwestern United States are discussed. The
      program's successes and opportunities for improvement are examined, as well as
      the recommendations for other nursing programs facing issues with student
      attrition.

PMID- 24328249
TI  - Preparing prelicensure and graduate nursing students to systematically
      communicate bad news to patients and families.
AB  - Communicating bad news, otherwise known as difficult conversations, is a complex
      communication skill that requires didactic learning and practical application.
      Students learn that what may be interpreted as bad news is determined by the
      recipient and not by the person who is delivering the news. Learning a systematic
      approach, such as the SPIKES (Setting, Perception, Invitation, Knowledge,
      Empathy, Strategy/Summary) mnemonic, prepares prelicensure and graduate nursing
      students for difficult conversations with patients and families in the clinical
      setting. Role-playing commonly includes clinical scenarios, and using video
      recording and playback of the encounters in such scenarios is one method of
      learning the systematic approach to communicating bad news. Follow-up practice
      after application in the clinical setting and feedback from faculty and mentors
      are essential for nursing students to achieve competence in this complex set of
      communication skills.

PMID- 24328251
TI  - Teaching undergraduate nursing students about environmental health: addressing
      public health issues through simulation.
AB  - Schools of nursing are challenged to find clinical placements in public health
      settings. Use of simulation can address situations unique to public health, with
      attention to specific concerns, such as environmental health. Environmental
      health is an integral part of public health nursing and is a standard of
      professional practice. Current simulations focus on acute care situations,
      offering limited scenarios with a public health perspective and excluding
      environmental health. This study's simulation scenario was created to enhance
      nursing students' understanding of public health concepts within an environmental
      health context. Outcomes from the simulation include the need for integration of
      environmental issues in public health teaching. Students stated that this
      scenario provided a broader understanding of the environmental influences that
      can affect the client's and family's health. This scenario fills a void in
      simulation content, while providing an interactive teaching and learning strategy
      to help students to apply knowledge to practice.

PMID- 24328252
TI  - Nano-FeS inhibits UO2 reoxidation under varied oxic conditions.
AB  - Bioreductive in situ treatment of U-contaminated groundwater can convert soluble
      U(VI) species to immobile reduced U(IV) solid phases such as UO2(s) to contain U
      movement. Once active bioremediation is halted, UO2 may be subsequently
      reoxidized if oxidants such as oxygen enter the reducing zone. However, iron
      sulfide minerals that form during bioreduction may serve as electron sources or
      oxygen scavengers and inhibit UO2 reoxidation upon oxygen intrusion. In this
      study, flow-through reactor experiments examined the abiotic kinetics of UO2
      oxidative dissolution in the presence of oxygen and nanoparticulate FeS as a
      function of pH, dissolved oxygen (DO) concentration, and FeS content. The UO2
      dissolution rates in the presence of FeS were over 1 order of magnitude lower
      than those in the absence of FeS under otherwise comparable oxic conditions. FeS
      effectively scavenged DO and preferentially reacted with oxygen, contributing to
      a largely unreacted UO2 solid phase during an "inhibition period" as determined
      by X-ray absorption spectroscopy (XAS). The removal of DO by FeS was significant
      but incomplete during the inhibition period, resulting in surface-oxidation
      limited dissolution and greater UO2 dissolution rate with increasing influent DO
      concentration and decreasing FeS content. Although the rate was independent of
      solution pH in the range of 6.1-8.1, the length of the inhibition period was
      shortened by substantial FeS dissolution at slightly acidic pH. The reducing
      capacity of FeS was greatest at basic pH where surface-mediated FeS oxidation
      dominated. 

PMID- 24328253
TI  - Target-triggered quadratic amplification for label-free and sensitive visual
      detection of cytokines based on hairpin aptamer DNAzyme probes.
AB  - The employment of DNAzyme probes for visual biodetections has received increasing
      interest recently due to the simple nature of this type of assay. However,
      achieving high sensitivity and detecting targets beyond nucleic acids remain two
      major challenges in DNAzyme-based visual detections. In this work, based on a new
      quadratic amplification strategy, we developed a sensitive and visual detection
      method for cytokines by using hairpin aptamer DNAzyme probes. The target
      cytokine, interferon gamma (IFN-gamma), associates with the aptamer sequences and
      unfolds the hairpin structure of the probes, leading to simultaneous recycling of
      the target IFN-gamma (assisted by Bst-polymerase) and the DNA sequences (aided by
      lambda exonuclease) to achieve quadratic amplification. This quadratic
      amplification results in the generation of numerous peroxidase-mimicking
      DNAzymes, which cause significantly intensified color change of the probe
      solution for highly sensitive detection of IFN-gamma by the naked eye down to 50
      pM. The proposed visual sensing method shows also high selectivity toward the
      target IFN-gamma and can be performed in homogeneous solutions with using
      completely unmodified, synthetic aptamer DNAzyme probes. These distinct
      advantages of our developed assay protocol make it a potential platform for
      detecting various types of biomolecules with careful probe designs. 

PMID- 24328254
TI  - Ultrasensitive and ultrawide range detection of a cardiac biomarker on a surface
      plasmon resonance platform.
AB  - One of the main challenges in the development of new analytical platforms for
      ultrasensitive bioaffinity detection is jointly achieving a wide dynamic range in
      target analyte concentration, especially for approaches that rely on multistep
      processes as a part of the signal amplification mechanism. In this paper, a new
      surface-based sandwich assay is introduced for the direct detection of B-type
      natriuretic peptide (BNP), an important biomarker for cardiac failure, at
      concentrations ranging from 1 aM to 500 nM. This was achieved using nanoparticle
      enhanced surface plasmon resonance (SPR) where a DNA aptamer is immobilized on a
      chemically modified gold surface in conjunction with the specific adsorption of
      antiBNP coated gold nanocubes in the presence of the biomarker target. A
      concentration detection range greater than eleven orders of magnitude was
      achieved through dynamic control of only the secondary nanoparticle probe
      concentration. Furthermore, detection at low attomolar concentrations was also
      achieved in undiluted human serum. 

PMID- 24328255
TI  - Formation of allenyl ketones, 3-ethynylcoumarins, and arylfurans, furylfurans,
      and furylthiophenes by flash vacuum thermolysis of 3-methylidenefuran-2(3H)-ones.
AB  - Flash vacuum thermolysis (FVT) of 3-methylidenefuran-2(3H)-ones 3 causes
      cheletropic extrusion of CO with formation of allenyl ketones 4. o-Chloro- and o
      bromophenylmethylidenefuranones also afford allenyl ketones upon flash vacuum
      thermolysis, but in addition, 3-ethynylcoumarins 6 are formed via E/Z
      isomerization of the methylidenefuranones, cyclization, halogen atom migration,
      and HCl (HBr) elimination. The presence of strongly electron-withdrawing groups
      (nitroaryl or acetyl) on the acylallene moiety causes rearrangement to give 2
      arylfurans 10 and 13 as well as 2-furylfurans and 2-furylthiophenes 16 by
      cyclization of the allenyl ketones. The reaction mechanisms are supported by
      calculations at the M06-2X/6-311+G(d,p) level of theory. 

PMID- 24328257
TI  - High-temperature measurements of the reactions of OH with ethylamine and
      dimethylamine.
AB  - The overall rate constants of hydroxyl radicals (OH) with ethylamine (EA:
      CH3CH2NH2) and dimethylamine (DMA: CH3NHCH3) were investigated behind reflected
      shock waves using UV laser absorption of OH radicals near 306.7 nm. tert-Butyl
      hydroperoxide (TBHP) was used as the fast source of OH at elevated temperatures.
      Test gas mixtures of individual amines and TBHP, diluted in argon, were shock
      heated to temperatures from 901 to 1368 K at pressures near 1.2 atm. The overall
      rate constants were determined by fitting the measured OH time-histories with the
      computed profiles using a detailed mechanism developed by Lucassen et al.
      (Combust. Flame 2012, 159, 2254-2279). Over the temperature range studied, the
      measured rate constants can be expressed as kEA+OH = 1.10 * 10(7).T(1.93)
      exp(1450/T) cm(3) mol(-1) s(-1), and kDMA+OH = 2.26 * 10(4).T(2.69) exp(1797/T)
      cm(3) mol(-1) s(-1). Detailed error analyses were performed to estimate the
      overall uncertainties of the measured reaction rate constants, and the estimated
      (2sigma) uncertainties were found to be +/-31% at 901 K and +/-22% at 1368 K for
      kEA+OH, and +/-29% at 925 K and +/-21% at 1307 K for kDMA+OH. Variational
      transition state theory was used to compute the H-abstraction rates by OH for
      ethylamine and dimethylamine, with the potential energy surface, geometries,
      frequencies, and electronic energies calculated by Galano and Alvarez-Idaboy (J.
      Chem. Theory Comput. 2008, 4, 322-327) at CCSD(T)/6-311++G(2d,2p) level of
      theory. The calculated reaction rate constants are in good agreement with the
      experimental data. 

PMID- 24328256
TI  - Toward single-molecule optical mapping of the epigenome.
AB  - The past decade has seen an explosive growth in the utilization of single
      molecule techniques for the study of complex systems. The ability to resolve
      phenomena otherwise masked by ensemble averaging has made these approaches
      especially attractive for the study of biological systems, where stochastic
      events lead to inherent inhomogeneity at the population level. The complex
      composition of the genome has made it an ideal system to study at the single
      molecule level, and methods aimed at resolving genetic information from long,
      individual, genomic DNA molecules have been in use for the last 30 years. These
      methods, and particularly optical-based mapping of DNA, have been instrumental in
      highlighting genomic variation and contributed significantly to the assembly of
      many genomes including the human genome. Nanotechnology and nanoscopy have been a
      strong driving force for advancing genomic mapping approaches, allowing both
      better manipulation of DNA on the nanoscale and enhanced optical resolving power
      for analysis of genomic information. During the past few years, these
      developments have been adopted also for epigenetic studies. The common principle
      for these studies is the use of advanced optical microscopy for the detection of
      fluorescently labeled epigenetic marks on long, extended DNA molecules. Here we
      will discuss recent single-molecule studies for the mapping of chromatin
      composition and epigenetic DNA modifications, such as DNA methylation. 

PMID- 24328258
TI  - Rapid labeling of metabolically engineered cell-surface glycoconjugates with a
      carbamate-linked cyclopropene reporter.
AB  - Metabolic oligosaccharide engineering is a valuable tool to monitor cellular
      carbohydrates. Here, we report the synthesis of a novel N-acyl-mannosamine
      derivative bearing a methylcyclopropene tag that is attached to the sugar via a
      carbamate moiety. This derivative undergoes rapid Diels-Alder reaction with
      inverse electron demand. We demonstrate that the cell's biosynthetic machinery
      incorporates this non-natural mannosamine derivative into glycoconjugates that
      can, subsequently, be labeled within less than 10 min with a new sulfo-Cy3
      tetrazine conjugate. Using this tetrazine-dye conjugate for the detection of the
      methylcyclopropene-tagged mannosamine derivative, we could achieve dual labeling
      of two different metabolically incorporated sugars combining a Diels-Alder
      reaction with inverse electron demand and a strain-promoted azide-alkyne
      cycloaddition which are carried out simultaneously in a single step. 

PMID- 24328259
TI  - Amide-I characteristics of helical beta-peptides by linear infrared measurement
      and computations.
AB  - In this work, we have examined the amide-I characteristics of three beta-peptide
      oligomers in typical helical conformations (two in 14-helix and one in 12/10
      helix), solvated in water, methanol, and chloroform, respectively. Local-mode
      frequencies and their distributions were computed using a molecular-mechanics
      force field based frequency map that was constructed on the basis of molecular
      dynamics simulations. The local-mode frequencies were found to be determined
      primarily by peptide backbone and side chain, rather by solvent, suggesting their
      local structural sensitivities. Intermode vibrational couplings computed using a
      transition dipole scheme were found to be very sensitive to peptide conformation,
      with their signs and magnitudes varying periodically along the peptide chain.
      Linear infrared absorption spectra of the three peptides, simulated using a
      frequency-frequency time-correlation function method, were found to be in fair
      agreement with experimental results. Normalized potential energy distribution
      analysis indicated that the amide-I mode can delocalize over a few amide units.
      However, the IR band structure appears to be more sophisticated in helical beta
      peptides than in helical alpha-peptides. 

PMID- 24328260
TI  - Order-disorder transition involving the A-site cations in Ln3+Mn3V4O12
      perovskites.
AB  - A crossover from the A-site-ordered double-perovskite structure with Im3 cubic
      symmetry to the simple-perovskite structure with Pnma orthorhombic symmetry is
      found in LnMn3V4O12 (Ln = La, Nd, Gd, Y, Lu) synthesized under high-pressure
      conditions. Relatively large Ln(3+) ions (La(3+), Nd(3+), and Gd(3+)) induce the
      a(+)a(+)a(+) in-phase cooperative tilting of the VO6 octahedra, resulting in the
      A-site-ordered double-perovskite structure with chemical composition
      Ln(3+)Mn(2+)3V(3.75+)4O12. Compounds with small Ln(3+) ions like Y(3+) and
      Lu(3+), on the other hand, crystallize with the Pnma simple-perovskite structure
      with chemical composition (Ln(3+)1/4Mn(2+)3/4)V(3.75+)O3, where the Ln(3+) and
      Mn(2+) ions are disordered at the A site. The random distribution of the small A
      site cation induces the a(-)b(+)a(-) tilting distortion of the VO6 octahedra. The
      observed phase crossover is well explained by the structural stability
      calculation based on the bond-valence-sum model, and the most stable crystal
      structure gives the smallest unit-cell volume. This A-site-cation size-dependent
      phase transition between the A-site-ordered double-perovskite and A-site
      disordered simple-perovskite structures in LnMn3V4O12 is thus a result of the
      structural stability due to the cooperative tilting of the VO6 octahedra. The
      Mn(2+) ions at the A'(A) site contribute local magnetic moments, whereas the
      V(3.75+) ions at the B site play a role in metallic conduction. The observed
      magnetic behaviors are consistent with the order-disorder distribution of the
      Mn(2+) ions at the A site, antiferromagnetism in the A-site-ordered double
      perovskites, and magnetic spin glass in the A-site-disordered simple perovskites.

PMID- 24328262
TI  - Self-assembled stimuli-responsive polyrotaxane core-shell particles.
AB  - Thermodynamically assembled core-shell nanocarriers are potential candidates for
      drug delivery applications due to their submicrometer size and the ability to
      load drugs into their hydrophobic core. Herein, we describe the formation of core
      shell particles that consist of noncovalent polymers, that is, polyrotaxanes
      (PRXs), that form an alpha-cyclodextrin (alphaCD) core surrounded by a corona of
      low-fouling poly(ethylene glycol) (PEG). The PRX core-shell particles are able to
      sequester small organic molecules, such as pyrene and calcein, releasing these
      small molecules during degradation. The small, cellular peptide, glutathione, was
      used to degrade the particles through the reductive cleavage of disulfide bonds
      that stabilize the individual PRX polymers. Cleavage of a single bond allows for
      the degradation of the supramolecular-polymer, making these PRX core-shell
      particles highly responsive. Furthermore, these particles demonstrate negligible
      cytotoxicity in mammalian cells, making them promising carriers for future drug
      delivery research. 

PMID- 24328261
TI  - Isotopic labeling experiments that elucidate the mechanism of DNA strand cleavage
      by the hypoxia-selective antitumor agent 1,2,4-benzotriazine 1,4-di-N-oxide.
AB  - The 1,2,4-benzotriazine 1,4-dioxides are an important class of potential
      anticancer drugs that selectively kill the low-oxygen (hypoxic) cells found in
      solid tumors. These compounds undergo intracellular one-electron enzymatic
      reduction to yield an oxygen-sensitive drug radical intermediate that partitions
      forward, under hypoxic conditions, to generate a highly reactive secondary
      radical that causes cell killing DNA damage. Here, we characterized
      bioreductively activated, hypoxia-selective DNA-strand cleavage by 1,2,4
      benzotriazine 1,4-dioxide. We found that one-electron enzymatic activation of
      1,2,4-benzotriazine 1,4-dioxide under hypoxic conditions in the presence of the
      deuterium atom donor methanol-d4 produced nondeuterated mono-N-oxide metabolites.
      This and the results of other isotopic labeling studies provided evidence against
      the generation of atom-abstracting drug radical intermediates and are consistent
      with a DNA-damage mechanism involving the release of hydroxyl radical from
      enzymatically activated 1,2,4-benzotriazine 1,4-dioxides. 

PMID- 24328263
TI  - Rapid anisotropic photoconductive response of ZnO-coated aligned carbon nanotube
      sheets.
AB  - We investigate the rapid and anisotropic UV-induced photoconductive response of
      hybrid thin films comprising zinc oxide (ZnO) nanowires (NWs) directly grown on
      horizontally aligned (HA-) carbon nanotube (CNT) sheets. The films exhibit
      anisotropic photoconductivity; along the CNTs, conductivity is dominated by the
      CNTs and the photoconductive gain is lower, whereas perpendicular to the CNTs the
      photoconductive gain is higher because transport is influenced by ZnO
      nanoclusters bridging CNT-CNT contacts. Because of the distributed electrical
      contact provided by the large number of ZnO NWs on top of the HACNT film, this
      hybrid nanoarchitecture has a significantly greater photocurrent than reported
      for single ZnO NW-based devices at comparable UV illumination intensity.
      Moreover, the hybrid architecture where a thin basal film of ZnO ohmically
      contacts metallic CNTs enables rapid transport of photogenerated electrons from
      ZnO to CNTs, resulting in sub-second photoresponse upon pulsed illumination. The
      built-in potential generated across ZnO-CNT heterojunctions competes with the
      externally applied bias to control the photocurrent amplitude and direction. By
      tuning the anisotropic conductivity of the CNT network and the morphology of the
      ZnO or potentially other nanostructured coatings, this material architecture may
      be engineered in the future to realize high-performance optical and chemical
      sensors. 

PMID- 24328264
TI  - Enhanced reductive dechlorination of tetrachloroethene dense nonaqueous phase
      liquid with EVO and Mg(OH)2.
AB  - In situ treatment of dense nonaqueous phase liquids (DNAPL) by enhanced reductive
      dechlorination (ERD) can be limited by contaminant toxicity, low pH, and
      challenges in effectively delivering electron donor. Flushing emulsified
      vegetable oil (EVO), colloidal Mg(OH)2 buffer, and a bioaugmentation culture (BC)
      through a zone containing neat tetrachloroethene (PCE) was effective in reducing
      contaminant toxicity, limiting pH declines, and accelerating bioenhanced
      dissolution of the DNAPL. In the effluent of porous media columns with little
      fine material, PCE concentrations reached a maximum of 40-50 times PCE aqueous
      solubility in water, demonstrating NAPL PCE was distributed throughout the 1.5 m
      column length. In a column treated with only EVO+BC, reductive dechlorination was
      limited. However, a single injection of EVO+Mg(OH)2+BC was effective in reducing
      PCE to below detection for over 400 days with a large increase in Cl(-) and
      dichloroethene (DCE), accelerating bioenhanced DNAPL dissolution. Dechlorination
      rates gradually increased over time with the rate of total ethene (TE) release
      from the Mg(OH)2+EVO+BC column reaching 5-6 times the TE release rate from the
      EVO+BC column. The accelerated dechlorination was likely due to both Mg(OH)2
      addition which limited pH declines from HCl, volatile fatty acids (VFAs), and
      inorganic carbon (IC) production, and formation of a mixed PCE-vegetable oil NAPL
      which provided a readily accessible electron donor, resulting in rapid PCE
      degradation with reduced PCE toxicity. 

PMID- 24328265
TI  - Colloidal solution-processed CuInSe2 solar cells with significantly improved
      efficiency up to 9% by morphological improvement.
AB  - We demonstrate here that an improvement in the green density leads to a great
      enhancement in the photovoltaic performance of CuInSe2 (CISe) solar cells
      fabricated with Cu-In nanoparticle precursor films via colloidal solution
      deposition. Cold-isostatic pressing (CIP) increases the precursor film density by
      ca. 20%, which results in an appreciable improvement in the microstructural
      features of the sintered CISe film in terms of a lower porosity, a more uniform
      surface morphology, and a thinner MoSe2 layer. The low-band-gap (1.0 eV) CISe
      solar cells with the CIP-treated films exhibit greatly enhanced open-circuit
      voltage (V(OC), typically from 0.265 to 0.413 V) and fill factor (FF, typically
      from 0.34 to 0.55), compared to the control devices. As a consequence, an almost
      3-fold increase in the average efficiency, from 3.0 to 8.2% (with the highest
      value of 9.02%), is realized. Diode analysis reveals that the enhanced V(OC) and
      FF are essentially attributed to the reduced reverse saturation current density
      and diode ideality factor. This is associated with suppressed recombination,
      likely due to the reduction in recombination sites at grain/air surfaces,
      intergranular interfaces, and defective CISe/CdS junctions. From the temperature
      dependences of V(OC), it is revealed that CIP-treated devices suffer less from
      interface recombination.

PMID- 24328266
TI  - A method of measurement of (239)Pu, (240)Pu, (241)Pu in high U content marine
      sediments by sector field ICP-MS and its application to Fukushima sediment
      samples.
AB  - An accurate and precise analytical method is highly needed for the determination
      of Pu isotopes in marine sediments for the long-term marine environment
      monitoring that is being done since the Fukushima Dai-ichi Nuclear Power Plant
      accident. The elimination of uranium from the sediment samples needs to be
      carefully checked. We established an analytical method based on anion-exchange
      chromatography and SF-ICP-MS in this work. A uranium decontamination factor of 2
      * 10(6) was achieved, and the U concentrations in the final sample solutions were
      typically below 4 pg mL(-1), thus no extra correction of (238)U interferences
      from the Pu spectra was needed. The method was suitable for the analysis of
      (241)Pu in marine sediments using large sample amounts (>10 g). We validated the
      method by measuring marine sediment reference materials and our results agreed
      well with the certified and the literature values. Surface sediments and one
      sediment core sample collected after the nuclear accident were analyzed. The
      characterization of (241)Pu/(239)Pu atom ratios in the surface sediments and the
      vertical distribution of Pu isotopes showed that there was no detectable Pu
      contamination from the nuclear accident in the marine sediments collected 30 km
      off the plant site. 

PMID- 24328267
TI  - Surface-assisted formation, assembly, and dynamics of planar organometallic
      macrocycles and zigzag shaped polymer chains with C-Cu-C bonds.
AB  - The formation, structure, and dynamics of planar organometallic macrocycles (meta
      terphenyl-Cu)n and zigzag-shaped one-dimensional organometallic polymers on a
      Cu(111) surface were studied with scanning tunneling microscopy (STM) and X-ray
      photoelectron spectroscopy (XPS). Vapor deposition of 4,4"-dibromo-meta-terphenyl
      (DMTP) onto Cu(111) at 300 K leads to C-Br bond scission and formation of C-Cu-C
      bonds, which connect neighboring meta-terphenyl fragments such that room
      temperature stable macrocycles and zigzag chains are formed. The chains self
      assemble to form islands, which are elongated in the direction of the chains. If
      DMTP is deposited onto Cu(111) held at 440 K, the island size is drastically
      increased (>200 * 200 nm(2)). STM sequences show the formation of ordered
      structures through reversible scission and reformation of the C-Cu-C bonds. The
      cyclic organometallic species such as the hexamer (meta-terphenyl-Cu)6 may
      represent intermediates in the surface-confined Ullmann synthesis of hydrocarbon
      macrocycles such as the recently discovered hyperbenzene. 

PMID- 24328268
TI  - Identification of palytoxin-Ca2+ complex by NMR and molecular modeling
      techniques.
AB  - More than 40 years after its isolation, the understanding of how palytoxin
      interacts with biological systems has yet to be fully determined. The Na(+),K(+)
      ATPase pump constitutes a molecular receptor for palytoxin that is able to
      convert the pump into an open channel, with consequent loss of cellular K(+) and
      remarkable rise of cytosolic Na(+) levels. In addition, a slight permeability to
      Ca(2+) is detected when palytoxin binds to the pump. It has been demonstrated
      that the increase of cytosolic free Ca(2+) concentration gives rise to downstream
      events ultimately leading to cell death. The widely accepted recognition of the
      dependence of important cellular events on calcium ion concentration propelled us
      to investigate the occurrence of palytoxin-Ca(2+) complex in aqueous solution by
      NMR- and molecular modeling-based approach. We identified two specific regions of
      palytoxin where Ca(2+) is preferentially coordinated. This study constitutes the
      first characterization of a calcium complex with palytoxin and, as such, is
      expected to support the investigation of the toxin molecular bioactivity. 

PMID- 24328269
TI  - Napyradiomycin derivatives, produced by a marine-derived actinomycete, illustrate
      cytotoxicity by induction of apoptosis.
AB  - The microbial production, isolation, and structure elucidation of four new
      napyradiomycin congeners (1-4) is reported. The structures of these compounds,
      which are new additions to the marine-derived meroterpenoids, were defined by
      comprehensive spectroscopic analysis and by X-ray crystallography. Using
      fluorescence-activated cell sorting (FACS) analysis, napyradiomycins 1-4 were
      observed to induce apoptosis in the colon adenocarcinoma cell line HCT-116,
      indicating the possibility of a specific biochemical target for this class of
      cytotoxins. 

PMID- 24328270
TI  - Global optimization of 8-10 atom palladium-iridium nanoalloys at the DFT level.
AB  - The global optimization of PdnIr(N-n) N = 8-10 clusters has been performed using
      the Birmingham Cluster Genetic Algorithm (BCGA). Structures were evaluated
      directly using density functional theory (DFT), which has allowed the
      identification of Ir and Ir-rich PdIr cubic global minima, displaying a strong
      tendency to segregate. The ability of the searches to find the putative global
      minimum has been assessed using a homotop search method, which shows a high
      degree of success. The role of spin in the system has been considered through a
      series of spin-restricted reoptimizations of BCGA-DFT minima. The preferred spin
      of the clusters is found to vary widely with composition, showing no overall
      trend in lowest-energy multiplicities. 

PMID- 24328271
TI  - Color tuning and white light emission via in situ doping of luminescent
      lanthanide metal-organic frameworks.
AB  - Isostructural lanthanide metal-organic frameworks (MOFs) are synthesized through
      the spontaneous self-assembly of H3BTPCA (1,1',1"-(benzene-1,3,5
      triyl)tripiperidine-4-carboxylic acid) ligands and lanthanide ions (we term these
      MOFs Ln-BTPCA, Ln = La(3+), Tb(3+), Sm(3+), etc.). Prompted by the observation
      that the different lanthanide ions have identical coordination environment in
      these MOFs, we explored and succeeded in the preparation of mixed-lanthanide
      analogues of the single-lanthanide MOFs by way of in situ doping using a mixture
      of lanthanide salts. With careful adjustment of the relative concentration of the
      lanthanide ions, the color of the luminescence can be modulated, and white light
      emission can indeed be achieved. The mechanisms possibly responsible for the
      observed photophysical properties of these mixed-lanthanide MOFs are also
      discussed. 

PMID- 24328272
TI  - Detection of the Sn(III) intermediate and the mechanism of the Sn(IV)/Sn(II)
      electroreduction reaction in bromide media by cyclic voltammetry and scanning
      electrochemical microscopy.
AB  - Fast-scan cyclic voltammetry (CV) and scanning electrochemical microscopy (SECM)
      were used to investigate the reduction of Sn(IV) as the hexabromo complex ion in
      a 2 M HBr-4 M NaBr medium. CV at scan rates to 100 V/s and SECM indicated the
      reaction pathway involves ligand-coupled electron transfer via an ECEC-DISP
      process: (1) one-electron reduction of Sn(IV)Br6(2-) to Sn(III)Br6(3-); (2)
      bromide dissociation of the reduced Sn(III)Br6(3-) to Sn(III)Br5(2-); (3)
      disproportionation of the reduced 2Sn(III)Br5(2-) to Sn(IV)Br5(-) and Sn(II)Br5(3
      ); (4) one-electron reduction of Sn(III)Br5(2-) to Sn(II)Br5(3-); (5) bromide
      dissociation from Sn(II)Br5 to Sn(II)Br4(2-). The intermediate Sn(III) species
      was confirmed by SECM(3-), where the Sn(III) generated at the Au tip was
      collected on a Au substrate in the tip generation/substrate collection mode when
      the distance between the tip and substrate was a few hundred nanometers. 

PMID- 24328273
TI  - Metabolomics for in situ environmental monitoring of surface waters impacted by
      contaminants from both point and nonpoint sources.
AB  - We investigated the efficacy of metabolomics for field-monitoring of fish exposed
      to wastewater treatment plant (WWTP) effluents and nonpoint sources of chemical
      contamination. Lab-reared male fathead minnows (Pimephales promelas, FHM) were
      held in mobile monitoring units and exposed on-location to surface waters
      upstream and downstream of the effluent point source, as well as to the actual
      effluent at three different WWTP sites in Minnesota. After four days of exposure,
      livers were collected, extracted, and analyzed by (1)H NMR spectroscopy and GC-MS
      to characterize responses of the hepatic metabolome. Multivariate statistical
      analysis revealed distinct metabolite profile changes in response to effluent
      exposure from each of the three WWTPs. Differences among locations (i.e.,
      upstream, downstream, and effluent) within each of the three sites were also
      identified. These observed differences comport with land-use and WWTP
      characteristics at the study sites. For example, at one of the sites, the
      metabolomic analyses suggested a positive interactive response from exposure to
      WWTP effluent and nearby nonpoint (likely agricultural related) contamination.
      These findings demonstrate the utility of metabolomics as a field-based technique
      for monitoring the exposure of fish to impacted surface waters. 

PMID- 24328274
TI  - Supramolecular assembly of multicomponent photoactive systems via cooperatively
      coupled equilibria.
AB  - Here, we show that the synergistic interplay between two binding equilibria,
      acting at different sites of a (Zn)phthalocyanine-amidine molecule (Pc1), enables
      the dissociation of the photoinactive phthalocyanine dimer (Pc1)2 into a three
      component system, in which a sequence of light harvesting, charge separation, and
      charge shift is successfully proven. The aforementioned dimer is assembled by
      dual amidine-Zn(II) coordination between neighboring Pc1 molecules and gives rise
      to high association constants (KD ~ 10(11) M(-1)). Such extraordinary stability
      hampers the individual binding of either carboxylic acid ligands through the
      amidine group or pyridine-type ligands through the Zn(II) metal atom to (Pc1)2.
      However, the combined addition of both ligands, which cooperatively bind to
      different sites of Pc1 through distinct noncovalent interactions, efficiently
      shifts the overall equilibrium toward a photoactive tricomponent species. In
      particular, when a fullerene-carboxylic acid (C60A) and either a dimethylamino
      pyridine (DMAP) or a phenothiazine-pyridine ligand (PTZP) are simultaneously
      present, the photoactivity is turned on and evidence is given for an electron
      transfer from photoexcited Pc1 to the electron-accepting C60A that affords the
      DMAP-Pc1(*+)-C60A(*-) or PTZP-Pc1(*+)-C60A(*-) radical ion pair states. Only in
      the latter case does a cascade of photoinduced electron transfer processes afford
      the PTZP(*+)-Pc1-C60A(*-) radical ion pair state. The latter is formed via a
      thermodynamically driven charge shift evolving from PTZP-Pc1(*+)-C60A(*-) and
      exhibits lifetimes that are notably longer than those of DMAP-Pc1(*+)-C60A(*-). 

PMID- 24328275
TI  - Critical exponents for solvent extraction resolved using SAXS.
AB  - The solvent extraction of an ionizable solute (H3PO4) from water into a water-in
      oil microemulsion, and subsequent organic phase splitting (known as third phase
      formation), has been recast as a critical phenomenon by linking system structure
      to solute concentration via a critical exponent. The transuranic extraction
      (TRUEX) system was investigated by extracting increasing concentrations of H3PO4
      into a microemulsion--consisting of two extractant amphiphiles (CMPO and TBP) and
      water in n-dodecane--and taking small-angle X-ray scattering (SAXS) measurements
      from the resulting solutions. The H3PO4 concentration at which phase splitting
      occurred was defined as the critical concentration (XC), and this was related to
      the precritical concentrations (X) by the reduced parameter epsilon = (X(C) -
      X)/X(C). The scattering intensity at the zero angle I(0), relating to the
      interaction between reverse micellar aggregates, conformed to the relation I(0) =
      I0epsilon(-gamma), with critical exponent gamma = 2.20. To check gamma, SAXS
      measurements were taken from the organic phase in situ with variable temperature
      through the point at which third phase formation initiates (the critical
      temperature), giving I(0) = I0t(-gamma), where t = (T - T(C))/T(C) and T(C) and T
      are the critical and precritical temperatures, with critical exponent gamma =
      2.55. These gamma values suggest third phase formation is a universal phenomenon
      manifest from a critical double point. Thus, solvent extraction is reduced to its
      fundamental physical roots where the system is not defined by detailed analysis
      of metrical properties but by linking the fundamental order to thermodynamic
      parameters via an exponent, working toward a more predictive understanding of
      third phase formation.

PMID- 24328276
TI  - Initiator-integrated 3D printing enables the formation of complex metallic
      architectures.
AB  - Three-dimensional printing was used to fabricate various metallic structures by
      directly integrating a Br-containing vinyl-terminated initiator into the 3D resin
      followed by surface-initiated atomic-transfer radical polymerization (ATRP) and
      subsequent electroless plating. Cu- and Ni-coated complex structures, such as
      microlattices, hollow balls, and even Eiffel towers, were prepared. Moreover, the
      method is also capable of fabricating ultralight cellular metals with desired
      structures by simply etching the polymer template away. By combining the merits
      of 3D printing in structure design with those of ATRP in surface modification and
      polymer-assisted ELP of metals, this universal, robust, and cost-effective
      approach has largely extended the capability of 3D printing and will make 3D
      printing technology more practical in areas of electronics, acoustic absorption,
      thermal insulation, catalyst supports, and others. 

PMID- 24328277
TI  - Antibody enrichment and mass spectrometry of albumin-Cys34 adducts.
AB  - Untargeted analyses of tryptic peptides of human serum albumin (HSA) have been
      used to investigate unknown exposures to reactive electrophiles (adductomics). To
      reduce the complexity of the analytical matrix and thereby enhance identification
      of adducts by liquid chromatography-high-resolution mass spectrometry (LC-HRMS),
      a polyclonal anti-T3 antibody was designed to capture Cys34 adducts in tryptic
      digests of HSA (T3 is the third largest tryptic peptide). Epitopes were selected
      from sequences at both C- and N-termini based on the three-dimensional structure
      of the T3 peptide to minimize the influence of modified Cys34 residues. The assay
      was simplified by attaching magnetic beads to the anti-T3 antibody. When applied
      to commercial HSA and to plasma samples from healthy humans and analyzed by LC
      HRMS, antibody treatment greatly reduced the background of non-T3 peptides in the
      sample matrix. Although other lipophilic HSA peptides were still present,
      presumably due to nonspecific binding to the antibody-magnetic-bead surfaces,
      their concentrations in antibody-treated samples were reduced about 6-fold
      compared to the same samples that had not been treated with the antibody.
      Analysis of antibody-enriched HSA digests from human plasma samples revealed 10
      modified T3 peptides of which 8 were identified from accurate masses. Identified
      peptides included Cys34 oxidation and cysteinylation products and modifications
      representing losses of water and Lys and transpeptidation of Arg.

PMID- 24328278
TI  - Optimization of PEDOT films in ionic liquid supercapacitors: demonstration as a
      power source for polymer electrochromic devices.
AB  - We report on the optimization of the capacitive behavior of poly(3,4
      ethylenedioxythiophene) (PEDOT) films as polymeric electrodes in flexible, Type I
      electrochemical supercapacitors (ESCs) utilizing ionic liquid (IL) and organic
      gel electrolytes. The device performance was assessed based on figures of merit
      that are critical to evaluating the practical utility of electroactive polymer
      ESCs. PEDOT/IL devices were found to be highly stable over hundreds of thousands
      of cycles and could be reversibly charged/discharged at scan rates between 500
      mV/s and 2 V/s depending on the polymer loading. Furthermore, these devices
      exhibit leakage currents and self-discharge rates that are comparable to state of
      the art electrochemical double-layer ESCs. Using an IL as device electrolyte
      allowed an extension of the voltage window of Type I ESCs by 60%, resulting in a
      2.5-fold increase in the energy density obtained. The efficacies of tjese PEDOT
      ESCs were assessed by using them as a power source for a high-contrast and fast
      switching electrochromic device, demonstrating their applicability in small
      organic electronic-based devices. 

PMID- 24328279
TI  - Adjustment of ON-state retention ability based on new donor-acceptor imides
      through structural tailoring for volatile device applications.
AB  - In this study, two D-A molecules NACANA and CANACA, based on carbazole (CA) donor
      and naphthalimide (NA) acceptor, with different D-A arrangement (A-D-A and D-A-D)
      were synthesized. The photophysical and electrochemical properties,
      microstructure and memory behaviors of both A-D-A and D-A-D molecules were
      systematically investigated. The fabricated devices ITO/NACANA or CANACA layer/Al
      with a simple sandwich configuration both exhibited volatile nature after
      shutting off the external electric field. Interestingly, NACANA showed ON-state
      retention time of ca. 12 min, longer than that of CANACA (ca. 6 min). The
      difference in retention ability of the programmed states could be assigned to the
      difference of the D-A arrangement. This type of retention ability adjustment by
      varying the arrangement of donor and acceptor segments may provide a guide of
      structure design for future organic-based specific memory devices with tunable
      volatile property. 

PMID- 24328280
TI  - Minimalist synthetic host with stacked guanidinium ions mimics the weakened
      hydration shells of protein-protein interaction interfaces.
AB  - Protein surfaces are complex solutes, and protein-protein interactions are
      specifically mediated by surface motifs that modulate solvation shells in poorly
      understood ways. We report herein a supramolecular host that is designed to mimic
      one of the most important recognition motifs that drives protein-protein
      interactions, the stacked arginine side chain. We show that it binds its guests
      and displays good selectivity in the highly competitive medium of pure, buffered
      water. We use a combination of experimental studies of binding and molecular
      dynamics simulations to build a cohesive picture of how this biomimetic host
      achieves the feat. The presence of the stacking element next to the guanidinium
      groups causes a decrease in the number of host-water hydrogen bonds, a decrease
      in the density of water around the host, and a decrease in water-water hydrogen
      bonds near the host. Experimental data using mixed organic/aqueous solvent
      systems confirm that this host relies on the hydrophobic effect in a way that the
      two control hosts do not. Our simulations and analysis provide detailed
      information on the linkage between (de)hydration and binding events in water in a
      way that could be applied to many aqueous supramolecular systems. 

PMID- 24328281
TI  - Determination of the rate constant for the OH(X2Pi) + OH(X2Pi) -> H2O + O(3P)
      reaction over the temperature range 295 to 701 K.
AB  - The rate constant for the radical-radical reaction OH(X(2)Pi) + OH(X(2)Pi) -> H2O
      + O((3)P) has been measured over the temperature and pressure ranges 295-701 K
      and 2-12 Torr, respectively, in mixtures of CF4, N2O, and H2O. The OH radical was
      produced by the 193 nm laser photolysis of N2O. The resulting O((1)D) atoms
      reacted rapidly with H2O to produce the OH radical. The OH radical was detected
      by high-resolution time-resolved infrared absorption spectroscopy using a single
      Lambda-doublet component of the OH(1,0) P1e/f(4.5) fundamental vibrational
      transition. A detailed kinetic model was used to determine the reaction rate
      constant as a function of temperature. These experiments were conducted in a new
      temperature controlled reaction chamber. The values of the measured rate
      constants are quite similar to the previous measurements from this laboratory of
      Bahng and Macdonald (J. Phys. Chem. A 2007 , 111 , 3850 - 3861); however, they
      cover a much larger temperature range. The results of the present work do not
      agree with recent measurements of Sangwan and Krasnoperov (J. Phys. Chem. A 2012
      , 116 , 11817 - 11822). At 295 K the rate constant of the title reaction was
      found to be (2.52 +/- 0.63) * 10(-12) cm(3) molecule(-1) s(-1), where the
      uncertainty includes both experimental scatter and an estimate of systematic
      errors at the 95% confidence limit. Over the temperature range of the
      experiments, the rate constant can be represented by k1a = 4.79 * 10(-18)T(1.79)
      exp(879.0/T) cm(3) molecule(-1) s(-1) with a uncertainty of +/-24% at the 2sigma
      level, including experimental scatter and systematic error.

PMID- 24328282
TI  - Tetrachloridometallate dianion-induced cucurbit[8]uril supramolecular assemblies
      with large channels and their potential applications for extraction coating on
      solid-phase microextraction fibers.
AB  - Q[8]-based porous materials were synthesized in the presence of [Md-blockCl4](2-)
      anions as structure inducers. The driving forces of the structure-directing
      effect of the [Md-blockCl4](2-) anions may be due to the ion-dipole interaction
      and hydrogen bonding between the [Md-blockCl4](2-) anions and =CH or ?CH2 groups
      on the backs of Q[8] molecules. Moreover, the tests of potential applications
      show that these porous materials can not only capture organic molecules through
      the cavity of Q[8] moieties but also adsorb larger organic molecules with
      different selectivities. 

PMID- 24328283
TI  - Leonurusoleanolides E-J, minor spirocyclic triterpenoids from Leonurus japonicus
      fruits.
AB  - Six new (leonurusoleanolides E-J, 1-6) and five known (7-11) nortriterpenoids
      were isolated and characterized from the dried fruits of Leonurus japonicus. They
      all contain a distinctive 19(18->17)-abeo-28-noroleanane-type spirocylclic
      skeleton with a trans or a cis acyl substituent at C-3 or C-23. Similar to the
      previously known leonurusoleanolides A/B (7/8) and C/D (9/10), compounds 1/2 and
      3/4 were also found to exist as equilibrium mixtures of trans and cis isomers.
      The isolated pure compounds and mixtures were evaluated for their cytotoxicity
      against a small panel of human cancer cell lines (BGC-823 and KE-97 gastric
      carcinoma, Huh-7 hepatocarcinoma, Jurkat T cell lymphoblasts, and MCF-7 breast
      adenocarcinoma) using the CellTiter-Glo luminescent cell viability assay method.
      Among them, (2alpha,3beta,17R*,18beta)-3-O-(trans-caffeoyl)-19(18->17)-abeo-28
      norolean-12-ene-2,18,23-triol (leonurusoleanolide J, 6) showed the most potent
      cytotoxic activity, with IC50 values less than 10 MUM. 

PMID- 24328284
TI  - Antimicrobial surfaces using covalently bound polyallylamine.
AB  - We investigated the antimicrobial properties of the cationic polymer
      polyallylamine (PA) when covalently bonded to glass. The objective was to obtain
      a robust attachment, yet still allow extension of the polymer chain into solution
      to enable interaction with the bacteria. The PA film displayed strong
      antimicrobial activity against Staphylococcus epidermidis , Staphylococcus aureus
      , and Pseudomonas aeruginosa , which includes both Gram-positive and Gram
      negative bacteria. Glass surfaces were prepared by a straightforward two-step
      procedure of first functionalizing with epoxide groups using 3
      glycidoxypropyltrimethoxy silane (GOPTS) and then exposing to PA so that the PA
      could bind via reaction of a fraction of its amine groups. The surfaces were
      characterized using X-ray photoelectron spectroscopy and Fourier transform
      infrared spectroscopy to verify the presence of the polymer on the surface, zeta
      potential measurements to estimate the surface charge of the films, and atomic
      force microscopy to determine the extension of the polymer chains into solution.
      Antimicrobial properties of these coatings were evaluated by spraying aqueous
      suspensions of bacteria on the functionalized glass slides, incubating them under
      agar, and counting the number of surviving cell colonies. 

PMID- 24328285
TI  - Synthesis and characterization of gyroidal mesoporous carbons and carbon
      monoliths with tunable ultralarge pore size.
AB  - Ordered mesoporous carbons with high pore accessibility are of great interest as
      electrodes in energy conversion and storage applications due to their high
      electric and thermal conductivity, chemical inertness, and low density. The metal
      and halogen-free synthesis of gyroidal bicontinuous mesoporous carbon materials
      with uniform and tunable pore sizes through bottom-up self-assembly of block
      copolymers thus poses an interesting challenge. Four double gyroidal mesoporous
      carbons with pore sizes of 12, 15, 20, and 39 nm were synthesized using
      poly(isoprene)-block-poly(styrene)-block-poly(ethylene oxide) (ISO) as structure
      directing triblock terpolymer and phenol-formaldehyde resols as carbon
      precursors. The highly ordered materials were thermally stable to at least 1600 
      degrees C with pore volumes of up to 1.56 cm(3) g(-1). Treatment at this
      temperature induced a high degree of sp(2)-hybridization and low microporosity.
      Increasing the resols/ISO ratio led to hexagonally packed cylinders with lower
      porosity. A single gyroid carbon network with high porosity of 80 vol % was
      obtained using a similar synthesis strategy. Furthermore, we present a method to
      fabricate monolithic materials of the gyroidal carbons with macroscopic shape and
      thickness control that exhibit an open and structured surface with gyroidal
      features. The gyroidal materials are ideally suited as electrode materials in
      fuel cells, batteries, and supercapacitors as their high, three-dimensionally
      connected porosity is expected to allow for good fuel or electrolyte
      accessibility and to prevent total pore blockage. 

PMID- 24328286
TI  - Decomposition of potent greenhouse gas sulfur hexafluoride (SF6) by
      Kirschsteinite-dominant stainless steel slag.
AB  - In this investigation, kirschsteinite-dominant stainless steel slag (SSS) has
      been found to decompose sulfur hexafluoride (SF6) with the activity higher than
      pure metal oxides, such as Fe2O3 and CaO. SSS is mainly made up of
      CaO.FeO.SiO2(CFS)/MgO.FeO.MnO(RO) phase conglomeration. The SF6 decomposition
      reaction with SSS at 500-700  degrees C generated solid MF2/MF3 and gaseous SiF4,
      SO2/SO3 as well as HF. When 10 wt % of SSS was replaced by Fe2O3 or CaO, the SF6
      decomposition amount decreased from 21.0 to 15.2 or 15.0 mg/g at 600  degrees C.
      The advantage of SSS over Fe2O3 or CaO in the SF6 decomposition is related to its
      own special microstructure and composition. The dispersion of each oxide
      component in SSS reduces the sintering of freshly formed MF2/MF3, which is severe
      in the case of pure metal oxides and inhibits the continuous reaction of inner
      components. Moreover, SiO2 in SSS reacts with SF6 and evolves as gaseous SiF4,
      which leaves SSS with voids and consequently exposes inner oxides for further
      reactions. In addition, we have found that oxygen significantly inhibited the SF6
      decomposition with SSS while H2O did not, which could be explained in terms of
      reaction pathways. This research thus demonstrates that waste material SSS could
      be potentially an effective removal reagent of greenhouse gas SF6. 

PMID- 24328287
TI  - Fabrication of highly uniform gel coatings by the conversion of surface-anchored
      metal-organic frameworks.
AB  - We report the fabrication of 3D, highly porous, covalently bound polymer films of
      homogeneous thickness. These surface-bound gels combine the advantages of metal
      organic framework (MOF) materials, namely, the enormous flexibility and the large
      size of the maximum pore structures and, in particular, the possibility to grow
      them epitaxially on modified substrates, with those of covalently connected gel
      materials, namely, the absence of metal ions in the deposited material, a robust
      framework consisting of covalent bonds, and, most importantly, pronounced
      stability under biological conditions. The conversion of a SURMOF (surface
      mounted MOF) yields a surface-grafted gel. These SURGELs can be loaded with
      bioactive compounds and applied as bioactive coatings and provide a drug-release
      platform in in vitro cell culture studies. 

PMID- 24328288
TI  - Ruthenium(II) tris(2,2'-bipyridine)-templated zinc(II) 1,3,5-tris(4
      carboxyphenyl)benzene metal organic frameworks: structural characterization and
      photophysical properties.
AB  - The ability to confine photoactive catalysts within metal organic framework (MOF)
      materials affords the opportunity to expand the functional diversity of these
      materials into solar-based applications. Here, two new Ru(II) tris(2,2'
      bipyridine) (RuBpy)-based photoactive materials derived from reactions between
      Zn(II) ions and 1,3,5-tris(4-carboxyphenyl)benzene and templated by the presence
      of RuBpy (RWLC-1 and RWLC-2) are described with regard to structure and RuBpy
      photophysics. RuBpy cations have been successfully encapsulated within the
      cavities (RWLC-1) and channels (RWLC-2) of the new negatively charged frameworks,
      both of which are synthesized simultaneously in a single reaction vial. Single
      crystal X-ray diffraction studies allowed for determination of the RuBpy position
      within crystal voids. RuBpy encapsulated in each of the two new MOFs exhibits
      biphasic triplet metal to ligand charge transfer ((3)MLCT) emission decay
      lifetimes (tauRWLC-1-fast = 237 ns, tauRWLC-1-slow = 1.60 MUs, tauRWLC-2-fast =
      171 ns, and tauRWLC-2-slow = 797 ns at 25  degrees C) consistent with two
      populations of RuBpy complexes, one being encapsulated in highly space-restricted
      cavities giving rise to a longer (3)MLCT lifetime, while the second is
      encapsulation within a larger nonperiodic pore or defect with a coencapsulated
      quencher giving rise to short emission lifetimes. Taken together, these results
      represent examples of the templating ability of RuBpy to produce novel materials
      with distinct photophysical environments of the encapsulated guests. 

PMID- 24328289
TI  - Self-assembling doxorubicin-tocopherol succinate prodrug as a new drug delivery
      system: synthesis, characterization, and in vitro and in vivo anticancer
      activity.
AB  - Self-assembled prodrugs forming nanoaggregates are a promising approach to
      enhance the antitumor efficacy and to reduce the toxicity of anticancer drugs. To
      achieve this goal, doxorubicin was chemically conjugated to d-alpha-tocopherol
      succinate through an amide bond to form N-doxorubicin-alpha-d-tocopherol
      succinate (N-DOX-TOS). The prodrug self-assembled in water into 250 nm
      nanostructures when stabilized with d-alpha-tocopherol poly(ethylene glycol) 2000
      succinate. Cryo-TEM analysis revealed the formation of nanoparticles with a
      highly ordered lamellar inner structure. NMR spectra of the N-DOX-TOS
      nanoparticles indicated that N-DOX-TOS is located in the core of the
      nanoparticles while PEG chains and part of the tocopherol are in the corona. High
      drug loading (34% w/w) and low in vitro drug release were achieved. In vitro
      biological assessment showed significant anticancer activity and temperature
      dependent cellular uptake of N-DOX-TOS nanoparticles. In vivo, these
      nanoparticles showed a greater antitumor efficacy than free DOX. N-DOX-TOS
      nanoparticles might have the potential to improve DOX-based chemotherapy. 

PMID- 24328290
TI  - Development of a spectroscopic technique for continuous online monitoring of
      oxygen and site-specific nitrogen isotopic composition of atmospheric nitrous
      oxide.
AB  - Nitrous oxide is an important greenhouse gas and ozone-depleting-substance. Its
      sources are diffuse and poorly characterized, complicating efforts to understand
      anthropogenic impacts and develop mitigation policies. Online, spectroscopic
      analysis of N2O isotopic composition can provide continuous measurements at high
      time resolution, giving new insight into N2O sources, sinks, and chemistry. We
      present a new preconcentration unit, "Stheno II", coupled to a tunable infrared
      laser direct absorption spectroscopy (TILDAS) instrument, to measure ambient
      level variations in (18)O and site-specific (15)N N2O isotopic composition at
      remote sites with a temporal resolution of <1 h. Trapping of N2O is quantitative
      up to a sample size of ~4 L, with an optimal sample size of 1200-1800 mL at a
      sampling frequency of 28 min. Line shape variations with the partial pressure of
      the major matrix gases N2/O2 and CO2 are measured, and show that characterization
      of both pressure broadening and Dicke narrowing is necessary for an optimal
      spectral fit. Partial pressure variations of CO2 and bath gas result in a linear
      isotopic measurement offset of 2.6-6.0 0/00 mbar(-1). Comparison of IR MS and
      TILDAS measurements shows that the TILDAS technique is accurate and precise, and
      less susceptible to interferences than IR MS measurements. Two weeks of
      measurements of N2O isotopic composition from Cambridge, MA, in May 2013 are
      presented. The measurements show significant short-term variability in N2O
      isotopic composition larger than the measurement precision, in response to
      meteorological parameters such as atmospheric pressure and temperature. 

PMID- 24328291
TI  - Biological and structural characterization of a naturally inspired material
      engineered from elastin as a candidate for tissue engineering applications.
AB  - The adoption of a biomimetic approach in the design and fabrication of innovative
      materials for biomedical applications is encountering a growing interest. In
      particular, new molecules are being engineered on the basis of proteins present
      in the extracellular matrix, such as fibronectin, collagen, or elastin. Following
      this approach scientists expect to be able not only to obtain materials with
      tailored mechanical properties but also to elicit specific biological responses
      inherited by the mimicked tissue. In the present work, a novel peptide,
      engineered starting from the sequence encoded by exon 28 of human tropoelastin,
      was characterized from a chemical, physical, and biological point of view. The
      obtained molecule was observed to aggregate at high temperatures, forming a
      material able to induce a biological effect similar to what elastin does in the
      physiological context. This material seems to be a good candidate to play a
      relevant role in future biomedical applications with special reference to
      vascular surgery. 

PMID- 24328292
TI  - Introducing Perspectives on Statistical Trends (POST).

PMID- 24328294
TI  - Interaction of lanthanide beta-diketonate complexes with polyvinylpyrrolidone:
      proton-controlled switching of Tb3+ luminescence.
AB  - In the present study the interaction of lanthanide beta-diketonate complexes with
      polyvinylpyrrolidone (PVP) has been systematically investigated using
      fluorescence spectroscopy. The emission of terbium complexes with
      hexafluoroacetylacetone (hfa) ligands is almost completely quenched by PVP in the
      absence of H(+) ions, while it is enhanced by more than 30 times in the presence
      of H(+) ions. Conversely, the H(+) ions increase the quenching efficiency of
      terbium complex with acetylacetone ligands. The strikingly different behavior of
      complexes with fluorinated and nonfluorinated beta-diketonates is accounted for
      by the interaction mechanism, in which the important role of hydrogen bonds is
      indicated. The proposed mechanism includes ion-dipol Coulombic interactions
      between negative charge localized on ligands O-C-CH2-C-O group and positive
      charge induced in N atom of PVP pyrrolidone group, as well as interactions
      through hydrogen bonds formed between ligand C-O groups and PVP, occurring
      directly or through solvent molecules. Additional stabilizing effect,
      significantly influencing the binding strength of ligands with PVP, results from
      hydrogen bonds formed by terminal (CF3 or CH3) substituents of ligands with C-O
      group of PVP. Importantly, the quenching and enhancement of luminescence of
      terbium complexes with hfa ligands in PVP solution is a reversible process. This
      enables one to obtain the emission switch-OFF-ON system triggered externally by
      H(+) ions, which can find possible application in the development of molecule
      based devices. 

PMID- 24328295
TI  - Mechanism of the formation of carboxylate from alcohols and water catalyzed by a
      bipyridine-based ruthenium complex: a computational study.
AB  - The catalytic mechanism for oxidizing alcohols to carboxylate in basic aqueous
      solution by the bipyridine-based ruthenium complex 2 (BIPY-PNN)Ru(H)(Cl)(CO)
      (Nat. Chem. 2013, 5, 122) is investigated by density functional theory (DFT) with
      the omegaB97X-D functional. Using water as the oxygen donor with liberation of
      dihydrogen represents a safe and clean process for such oxidations. Under NaOH,
      the active catalyst is 3 (BIPY-PNN)Ru(H)(CO). Four steps are involved:
      dehydrogenation of alcohol to aldehyde (Step 1); coupling of aldehyde and water
      to form the gem-diol (Step 2); dehydrogenation of gem-diol to carboxylic acid
      (Step 3); and deprotonation of carboxylic acid to carboxylate anion under base
      (Step 4). The dehydrogenations of alcohol (Step 1) and gem-diol (Step 3) prefer
      the double hydrogen transfer mechanism to the beta-H elimination mechanism. The
      coupling of aldehyde and water (Step 2) proceeds through cleavage of water by
      catalyst 3 followed by concerted hydroxyl and hydrogen transfer to the aldehyde.
      The formation of the carboxylate anion occurs via direct deprotonation of the
      carboxylic acid under base (Step 4), while in the absence of base a stable
      carboxylic acid-addition complex 6 was formed. Added base was found to play
      important roles in the generation of catalyst 3 from both the stable carboxylic
      acid-addition complex 6 and its chloride precursor complex 2. The
      chemoselectivity for the formation of carboxylic acid rather than ester is
      ascribed to the favorable cleavage of water and the subsequent generation of the
      stable carboxylate anion that leads to carboxylic acid upon acidification. 

PMID- 24328296
TI  - Langmuir-Schaefer films for aligned carbon nanotubes functionalized with a
      conjugate polymer and photoelectrochemical response enhancement.
AB  - Single-walled carbon nanotubes (SWCNTs) were suspended in 1,2-dichloroethane by
      noncovalent functionalization with a low-band-gap conjugated polymer 1
      alternating dialkoxyphenylene-bisthiophene units with benzo[c][2,1,3]thiadiazole
      monomeric units. The suspended 1/SWCNT blend was transferred onto different solid
      substrates by the Langmuir-Schaefer deposition method, resulting in films with a
      high percentage of aligned nanotubes. Photoelectrochemical characterization of
      1/SWCNT thin films on indium-tin oxide showed the benefits of SWCNT alignment for
      photoconversion efficiency. 

PMID- 24328297
TI  - Anionogenic mixed valency in KxBa1-xO2-delta.
AB  - We have synthesized members of an isostructural solid solution series KxBa1-xO2
      delta (x < 0.41, delta < 0.11) containing mixed-valent dioxygen anions. Synthesis
      in liquid ammonia solution allows a continuous range of compounds to be prepared.
      X-ray and neutron diffraction show that KxBa1-xO2-delta adopts the tetragonal
      rocksalt-derived structure of the end members KO2 and BaO2, without any
      structural phase transition down to 5 K, the lowest temperature studied here. We
      identify four oxygen-oxygen stretching modes above 750 cm(-1) in the measured
      Raman spectra, unlike the spectra of KO2 and BaO2 which both contain just a
      single mode. We use density functional theory calculations to show that the
      stretching modes in KxBa1-xO2-delta arise from in-phase and anti-phase coupling
      of the stretching of nearest-neighbor oxygen dimers when the valence state of the
      dimers lies between -1 and -2 because of mixed cation coordination. This coupling
      is a direct signature of a novel type of anionogenic mixed valency. 

PMID- 24328298
TI  - Scalar relaxation of the second kind - a potential source of information on the
      dynamics of molecular movements. 2. Magnetic dipole moments and magnetic
      shielding of bromine nuclei.
AB  - In this paper, we continue the exploration of possibilities, limitations, and
      methodological problems of the studies based on measurements of the nuclear spin
      relaxation rates running via the scalar relaxation of the second kind (SC2)
      mechanism. The attention has been focused on the (13)C-(79)Br and (13)C-(81)Br
      systems in organic bromo compounds, which are characterized by exceptionally
      small differences of Larmor frequencies, DeltaomegaCBr, of the coupled nuclei.
      This unique property enables experimental observation of longitudinal SC2
      relaxation of (13)C nuclei, which makes investigation of the SC2 relaxation rates
      an attractive experimental method of determination of spin-spin coupling
      constants and relaxation rates of quadrupole bromine nuclei, both types of
      parameters being hardly accessible by direct measurements. A careful examination
      of the methodology used in SC2 relaxation studies of carbon-bromine systems
      reveals, however, some disturbing facts that could burden the results with
      systematic inaccuracies. Namely, the way of calculating the Larmor frequency
      differences between (13)C and bromine isotopes, DeltaomegaCBr, may cause some
      reservations. In this work, the values of (79)Br and (81)Br magnetogyric ratios
      have been rechecked using bromine NMR data for the KBr.Kryptofix 222 complex in
      acetonitrile solution and the results of the advanced calculations of the
      magnetic shielding of the bromine nucleus in the Br(-) anion. Moreover, it has
      been pointed out that in the case of (13)C-(79)Br, the magnetic shielding of the
      bromine nucleus in the investigated molecule must not be neglected during the
      calculation of the DeltaomegaCBr parameter. Some recommendations concerning the
      exploitation of available theoretical methods to calculate bromine shielding
      constants for bromo compounds have also been formulated, keeping in mind
      relativistic effects. 

PMID- 24328299
TI  - Rapid method for glutathione quantitation using high-performance liquid
      chromatography with coulometric electrochemical detection.
AB  - A rapid, sensitive, and direct method (without derivatization) was developed for
      the detection of reduced glutathione (GSH) in cultured hepatocytes (HepG2 cells)
      using high-performance liquid chromatography with electrochemical detection (HPLC
      ECD). The method was validated according to the guidelines of the U.S. Food and
      Drug Administration in terms of linearity, lower limit of quantitation (LOQ),
      lower limit of detection (LOD), precision, accuracy, recovery, and stabilities of
      GSH standards and quality control samples. The total analysis time was 5 min, and
      the retention time of GSH was 1.78 min. Separation was carried out isocratically
      using 50 mM sodium phosphate (pH 3.0) as a mobile phase with a fused-core column.
      The detector response was linear between 0.01 and 80 MUmol/L, and the regression
      coefficient (R(2)) was >0.99. The LOD for GSH was 15 fmol, and the intra- and
      interday recoveries ranged between 100.7 and 104.6%. This method also enabled the
      rapid detection (in 4 min) of other compounds involved in GSH metabolism such as
      uric acid, ascorbic acid, and glutathione disulfite. The optimized and validated
      HPLC-ECD method was successfully applied for the determination of GSH levels in
      HepG2 cells treated with buthionine sulfoximine (BSO), an inhibitor, and alpha
      lipoic acid (alpha-LA), an inducer of GSH synthesis. As expected, the amount of
      GSH concentration-dependently decreased with BSO and increased with alpha-LA
      treatments in HepG2 cells. This method could also be useful for the quantitation
      of GSH, uric acid, ascorbic acid, and glutathione disulfide in other biological
      matrices such as tissue homogenates and blood. 

PMID- 24328300
TI  - Ternary hybrid nanoparticle isomers: directing the nucleation of Ag on Pt
      Fe(3)O(4) using a solid-state protecting group.
AB  - Colloidal hybrid nanoparticles are an important class of materials that
      incorporate multiple nanoparticles into a single system through solid-state
      interfaces, which can result in multifunctionality and the emergence of
      synergistic properties not found in the individual components. These hybrid
      structures are typically produced using seeded-growth methods, where preformed
      nanoparticles serve as seeds onto which additional domains are added through
      subsequent reactions. For hybrid nanoparticles that contain more than two
      domains, multiple configurations with distinct connectivities and functionalities
      are possible, and these can be considered as nanoparticle analogues of molecular
      isomers. However, accessing one isomer relative to others in the same hybrid
      nanoparticle system is challenging, particularly when the formation of a target
      isomer is disfavored relative to more stable or synthetically accessible
      configurations. Here, we show that an iron oxide shell installed onto the Pt
      domain of Pt-Fe3O4 hybrid nanoparticles serves as a solid-state protecting group
      that can direct the nucleation of a third domain to an otherwise disfavored site.
      Under traditional conditions, Ag nucleates exclusively onto the Pt domain of Pt
      Fe3O4 heterodimers, resulting in the formation of the Ag-Pt-Fe3O4 heterotrimer
      isomer. When the Pt surface is covered with an iron oxide protecting group, the
      nucleation of Ag is redirected onto the Fe3O4 domain, producing the distinct and
      otherwise inaccessible Pt-Fe3O4-Ag isomer. Similar results are obtained for the
      Au-Pt-Fe3O4 system, where formation of the favored Au-Pt-Fe3O4 configuration is
      blocked by the iron oxide protecting group. The thickness of the iron oxide shell
      that protects the Pt domain can be systematically tuned by adjusting the ratio of
      oleic acid to iron pentacarbonyl during the synthesis of the Pt-Fe3O4
      heterodimers, and this insight is important for controllably implementing the
      protecting group chemistry. 

PMID- 24328301
TI  - Diverse self-assembly from predesigned conformationally flexible pentanuclear
      clusters observed in a ternary copper(II)-triazolate-sulfoisophthalate system:
      synthesis, structure, and magnetism.
AB  - Self-assembly from the predesigned Cu(II)5 secondary building unit (SBU) in the
      ternary Cu(II)-triazolate-sulfoisophthalate system generates three interesting
      magnetic samples: an open pillared-layer framework with nanosized Cu(II)30
      metallamacrocycle-based sublayer (1), a (3,6)-connected 2-fold interpenetrating
      network consisting of alternating Cu(II)5 and Cu(II)1 cores (2), and a (4,8)
      connected architecture constructed from centrosymmetric Cu(II)7 clusters and four
      branched 5-sulfoisophthalate (sip(3-)) connectors (3). These various structures
      significantly result from the variable connectivity and the slight expansion of
      the predetermined conformationally flexible Cu(II)5 SBUs. Furthermore, these
      intriguing structural motifs in 1-3 essentially induce different magnetic
      phenomena. A field-dependent metamagnetic transition from antiferromagnetic
      ordering to weak ferromagnetism is observed in the frustrated Cu(II)30-based
      sublayer of 1. The paramagnetic Cu(II)1 core in 2 virtually contributes to an S =
      (1)/2 spin ground state due to the completely compensated magnetic moment in the
      1,2,3-triazolate (ta(-))-bridged Cu(II)5 cluster containing ribbon. In contrast,
      strong antiferromagnetic interactions in the locally centrosymmetric Cu(II)7
      cluster lead to an overall S = (1)/2 spin ground state of 3. Thus, the SBU
      derived self-assembly strategy provides important hints for polymetallic cluster
      based high-dimensional magnetic materials, which also brings a new vision for the
      design and construction of novel functional materials. 

PMID- 24328302
TI  - Protein kinase and HDAC inhibitors from the endophytic fungus Epicoccum nigrum.
AB  - A chemical investigation of the endophytic fungus Epicoccum nigrum isolated from
      leaves of Mentha suaveolens collected in Morocco resulted in the isolation of
      five new polyketides, epicocconigrones A and B (1 and 2), 3-methoxyepicoccone B
      (3), 3-methoxyepicoccone (4), and 2,3,4-trihydroxy-6-(methoxymethyl)-5
      methylbenzaldehyde (5), together with five known compounds (6-10). The structures
      of the new compounds were unambiguously determined by extensive analysis of the
      1D and 2D NMR and mass spectroscopic data. Compounds 1 and 10 showed potent
      inhibition of at least 15 protein kinases with IC50 values ranging from 0.07 to
      9.00 MUM. Moreover, compounds 1 and 10 inhibited histone deacetylase (HDAC)
      activities with IC50 values of 9.8 and 14.2 MUM, respectively. A preliminary
      structure-activity relationship is discussed. Interestingly, compounds 1 and 10
      exert mainly cytostatic effects in human lymphoma RAJI and U-937 cell lines. 

PMID- 24328303
TI  - Template-free synthesis of hematite photoanodes with nanostructured ATO
      conductive underlayer for PEC water splitting.
AB  - Hematite is a promising semiconductor candidate for PEC water splitting. However,
      hematite is far well short of the theoretical value of solar-to-fuel conversion
      efficiency because of the fast recombination of photogenerated carriers. To
      address this limitation, a facile template-free preparation of hematite
      photoanode with nanostructured ATO (antimony-doped tin oxide) conductive
      underlayer served as a scaffold to transport photogenerated electron was
      developed to decrease the recombination opportunities of the carriers.
      Furthermore, the constructed ATO scaffold could also increase the light
      absorption of hematite and the number of the carriers, resulting in better PEC
      performance of hematite. 

PMID- 24328304
TI  - Self-association and nitroaromatic-induced deaggregation of pyrene substituted
      pyridine amides.
AB  - The self-assembly features of the bis-pyrene methyl amide functionalized pyridine
      and benzene "tweezers" 1 and 2 were studied in organic solution and in the solid
      state. These systems were found to display remarkably different self-association
      features and optical properties, which was rationalized by control experiments
      using compounds bearing pyrenemethyl esters, alkyl groups, or a single pyrene
      substituent (3-6). As dilute solutions in chloroform, tweezers 1 displays both
      pyrene monomer and excimer emission features reflecting intramolecular contacts
      between the pyrene subunits. At higher concentrations in chloroform, as well as
      in the solid state, tweezers 1 self-assembles to form a linear supramolecular
      polymer. In contrast, tweezers 2 does not interact in an intermolecular fashion
      and photoexcitation produces emission features characteristic of a pyrene
      monomer. DFT (density functional theory) and TDDFT (time dependent density
      functional theory) calculations revealed that the lowest vertical transitions are
      forbidden and that S1 of 1 is an emissive state. In contrast to 1 and 2, both
      pyrene-free control systems 5 and 6 were found to form linearly self-assembled
      supramolecular arrays in the solid state, albeit of differing structure. Upon
      exposure to trinitrobenzene (TNB), the self-assembled structures formed from 1
      undergo deaggregation to form TNB complexes. This change is reflected in both an
      easily discernible color change and a quenching of the fluorescence emission
      intensity. Changes in the optical features were also seen in the case of 2.
      However, notable differences between these two ostensibly similar systems were
      seen. 

PMID- 24328306
TI  - Biofunctionalized gadolinium-containing prussian blue nanoparticles as multimodal
      molecular imaging agents.
AB  - Molecular imaging agents enable the visualization of phenomena with cellular and
      subcellular level resolutions and therefore have enormous potential in improving
      disease diagnosis and therapy assessment. In this article, we describe the
      synthesis, characterization, and demonstration of core-shell, biofunctionalized,
      gadolinium-containing Prussian blue nanoparticles as multimodal molecular imaging
      agents. Our multimodal nanoparticles combine the advantages of MRI and
      fluorescence. The core of our nanoparticles consists of a Prussian blue lattice
      with gadolinium ions located within the lattice interstices that confer high
      relaxivity to the nanoparticles providing MRI contrast. The relaxivities of our
      nanoparticles are nearly nine times those observed for the clinically used
      Magnevist. The nanoparticle MRI core is biofunctionalized with a layer of
      fluorescently labeled avidin that enables fluorescence imaging. Biotinylated
      antibodies are attached to the surface avidin and confer molecular specificity to
      the nanoparticles by targeting cell-specific biomarkers. We demonstrate our
      nanoparticles as multimodal molecular imaging agents in an in vitro model
      consisting of a mixture of eosinophilic cells and squamous epithelial cells. Our
      nanoparticles specifically detect eosinophilic cells and not squamous epithelial
      cells, via both fluorescence imaging and MRI in vitro. These results suggest the
      potential of our biofunctionalized Prussian blue nanoparticles as multimodal
      molecular imaging agents in vivo. 

PMID- 24328305
TI  - Increased outer arm and core fucose residues on the N-glycans of mutated alpha-1
      antitrypsin protein from alpha-1 antitrypsin deficient individuals.
AB  - Alpha-1 antitrypsin (AAT) is the major physiological inhibitor of a range of
      serine proteases, and in the lung, it maintains a protease-antiprotease balance.
      AAT deficiency (AATD) is an autosomal co-dominant condition with the Z mutation
      being the most common cause. Individuals homozygous for Z (PiZZ) have low levels
      of circulating mutant Z-AAT protein leading to premature emphysematous lung
      disease. Extensive glycoanalysis has been performed on normal AAT (M-AAT) from
      healthy individuals and the importance of glycosylation in affecting the immune
      modulatory roles of AAT is documented. However, no glycoanalysis has been carried
      out on Z-AAT from deficient individuals to date. In this study, we investigate
      whether the glycans present on Z-AAT differ to those found on M-AAT from healthy
      controls. Plasma AAT was purified from 10 individuals: 5 AATD donors with the
      PiZZ phenotype and 5 PiMM healthy controls. Glycoanalysis was performed employing
      N-glycan release, exoglycosidase digestion and UPLC analysis. No difference in
      branched glycans was identified between AATD and healthy controls. However, a
      significant increase in both outer arm (alpha1-3) (p = 0.04) and core (alpha1-6)
      fucosylated glycans (p < 0.0001) was found on Z-AAT compared to M-AAT. This study
      has identified increased fucosylation on N-glycans of Z-AAT indicative of ongoing
      inflammation in AATD individuals with implications for early therapeutic
      intervention. 

PMID- 24328307
TI  - Chitin nanocrystal-xyloglucan multilayer thin films.
AB  - For the first time, the adsorption of xyloglucan (XG) on chitin nanocrystals
      (ChiNC) surface was proved using quartz crystal microbalance with dissipation
      (QCM-D) and by successfully building up spin-coated assisted layer-by-layer (LbL)
      structures on solid substrates. Several parameters in the adsorption process,
      such as ChiNC concentrations (0.5-3.0 g L(-1)), number of layers, or the outmost
      layer material (ChiNC or XG), were investigated to better understand the
      fabrication process of multilayer films. The thickness of the homogeneous film
      increased linearly with the number of bilayers, with an average thickness per
      bilayer of 12.3 nm. Additionally surface morphology was studied by atomic force
      microscopy (AFM), which revealed an almost completely covered surface after the
      adsorption of ChiNC. The final structures were found to have semireflective
      properties capable of being tuned by adjusting the ChiNC dispersion parameters. 

PMID- 24328309
TI  - Reactions of a tungsten-germylyne complex with alpha,beta-unsaturated ketones:
      complete cleavage of the W=Ge bond and formation of two types of eta3
      germoxyallyl tungsten complexes.
AB  - Germylyne complex Cp*(CO)2W=Ge{C(SiMe3)3} (1) reacted with two molecules of
      RC(O)CH?CH2 (R = Me, Et) to give eta(3)-allyl complexes, in which an
      oxagermacyclopentene framework was bound to an eta(3)-allyl ligand through an
      oxygen atom. In the reaction with alpha-Me-substituted MeC(O)C(Me)?CH2, 1 reacted
      with only one molecule of the substrate to give another type of eta(3)-allyl
      complex, in which a five-membered oxagermacyclopentenyl ring was coordinated to
      the W center in an eta(3) fashion. Both reactions resulted in unprecedented
      complete cleavage of a W=Ge triple bond. 

PMID- 24328308
TI  - Ultrasensitive apurinic/apyrimidinic endonuclease 1 immunosensing based on self
      enhanced electrochemiluminescence of a Ru(II) complex.
AB  - An alternative "signal on" immunosensor for ultrasensitive detection of
      apurinic/apyrimidinic endonuclease 1 (APE-1) was designed utilizing the self
      enhanced electrochemiluminescence (ECL) of a novel Ru(II) complex functionalized
      coil-like nanocomposite as signal labels. The desirable self-enhanced ECL
      luminophore was achieved by combining the coreactant of poly(ethylenimine) (PEI)
      and the luminophor of bis(2,2'-bipyridine)-5-amino-1,10-phenanthroline
      ruthenium(II) [Ru(bpy)2(5-NH2-1,10-phen)(2+)] to form one novel Ru(II) complex,
      which exhibited significantly enhanced ECL efficiency and stability. Moreover,
      the carbon nanotubes (CNTs) were employed as nanocarriers for self-enhanced
      Ru(II) complex loading via pi-pi stacking to obtain the coil-like nanocomposite
      to act as signal probe. Compared with traditional ECL immunoassay, our proposed
      strategy is simple and sensitive, avoiding the adding of any coreactant into
      testing solution for signal amplification, and shows a detection limit down to
      subfemtogram per milliliter level under the optimized experimental condition. 

PMID- 24328310
TI  - Comment on "cancer risk from incidental ingestion exposures to PAHs associated
      with coal-tar-sealed pavement".

PMID- 24328311
TI  - Two dimensional imaging of the virtual source of a supersonic beam: helium at 125
      K.
AB  - Here we present the first two-dimensional images of the virtual source of a
      supersonic helium expansion. The images were obtained using a free-standing
      Fresnel zone plate with an outermost zone width of 50 nm as imaging lens and a
      beam cooled to around 125 K. The nozzle diameter was 10 MUm. The virtual source
      diameter was found to increase with stagnation pressure from 140 +/- 30 MUm at po
      = 21 bar up to 270 +/- 25 MUm at po = 101 bar. The experimental results are
      compared to a theoretical model based on the solution of the Boltzmann equation
      by the method of moments. The quantum mechanical cross sections used in the model
      have been calculated for the Lennard-Jones (LJ) and the Hurly-Moldover (HM)
      potentials. By using a scaling of the perpendicular temperature that parametrizes
      the perpendicular velocity distribution based on a continuum expansion approach,
      the LJ potential shows a good overall agreement with the experiment. However, at
      higher pressures the data points lie in between the two theoretical curves and
      the slope of the trend is more similar to the HM curve. Real gas corrections to
      enthalpy are considered but they affect the results less than the experimental
      errors. 

PMID- 24328312
TI  - Processing treatments for mitigating acrylamide formation in sweetpotato French
      fries.
AB  - Acrylamide formation in sweetpotato French fries (SPFF) is likely a potential
      health concern as there is an increasing demand for good-quality fries from
      carotene-rich sweetpotatoes (SP). This is the first report on acrylamide
      formation in SPFF as affected by processing methods. Acrylamide levels in SPFF
      from untreated SP strips fried at 165  degrees C for 2, 3, and 5 min were 124.9,
      255.5, and 452.0 ng/g fresh weight, which were reduced by about 7 times to 16.3,
      36.9, and 58.3 ng/g, respectively, when the strips were subjected to processing
      that included water blanching and soaking in 0.5% sodium acid pyrophosphate
      before frying. An additional step of strip soaking in 0.4% calcium chloride
      solution before par-frying increased the calcium content from 0.2 to 0.8 mg/g and
      decreased the acrylamide levels to 6.3, 17.6, and 35.4 ng/g, respectively. SPFF
      with acrylamide level of <100 ng/g or several times lower than that of white
      potato French fries can be obtained by integrating processing treatments commonly
      used in the food industry. 

PMID- 24328313
TI  - Effect of polyvalent ions in the formation of ionic-liquid-based aqueous biphasic
      systems.
AB  - Two main approaches were combined aiming at evaluating the impact of polyvalent
      salt cations on the formation of ionic-liquid-based aqueous biphasic systems
      (ABS): (i) experimental determination of a large array of ternary phase diagrams
      composed of sodium-, magnesium-, and aluminum-based salts with 1-butyl-3
      methylimidazolium-based ionic liquids and (ii) determination of the ions
      speciation in each of these systems. The results here reported show, for the
      first time, that the phase behavior of ionic-liquid-based aqueous biphasic
      systems is not only dominated by the ability of the strong and "free" salting-out
      ions to interact with water creating thus hydration complexes but also a result
      of the interactions occurring between the different ions and, particularly, on
      their speciation in aqueous solutions. The gathered data indicate that the higher
      the salt ion valence, the more complex is its speciation with a number of
      different species in aqueous media present. Further results based on NMR
      spectroscopy and a proper analysis of the pH influence clearly demonstrated the
      impact of ion speciation through the phase separation and ABS formation. 

PMID- 24328314
TI  - Implantation length and thermal stability of interstitial ar atoms in boron
      nitride nanotents.
AB  - Hyperthermal atoms may be implanted beneath single layers of graphene or
      hexagonal boron nitride (h-BN) on a substrate. For the case of h-BN on rhodium,
      which is a corrugated honeycomb superstructure with a periodicity of 3.2 nm, Ar
      atoms are implanted at distinct interstitial sites within the supercell, where
      the h-BN is weakly bound to the substrate. These peculiar structures are
      reminiscent of "nanotents" with an ultimately thin "rainfly". Here we explore the
      implantation length (i.e., the distance the atoms move before they come to rest
      as interstitial defects) and the thermal stability of these atomic agglomerates
      above room temperature. The results are obtained by variable-temperature scanning
      tunneling microscopy and density functional theory calculations. 

PMID- 24328316
TI  - Synthesis and properties of the first [Au(dien)(N-heterocycle)]3+ compounds.
AB  - Novel Au(III)(dien)(N-heterocycle) compounds, including the first Au(III)N3(N
      purine) examples, are reported. The acidity of the dien ligand is affected by the
      nature of the fourth ligand as a leaving group. The metal center of [Au(dien)(N
      heterocycle)](3+) compounds was shown to be more stable to reduction than when
      Cl(-) is present, with consequences for reactivity with biomolecules:
      specifically, significant enhancement of pi-pi-stacking interactions with
      tryptophan relative to isostructural and isoelectronic platinum(II) and
      palladium(II) compounds. 

PMID- 24328315
TI  - Dermal uptake of organic vapors commonly found in indoor air.
AB  - Transdermal uptake directly from air is a potentially important yet largely
      overlooked pathway for human exposure to organic vapors indoors. We recently
      reported (Indoor Air 2012, 22, 356) that transdermal uptake directly from air
      could be comparable to or larger than intake via inhalation for many semivolatile
      organic compounds (SVOCs). Here, we extend that analysis to approximately eighty
      organic compounds that (a) occur commonly indoors and (b) are primarily in the
      gas-phase rather than being associated with particles. For some compounds, the
      modeled ratio of dermal-to-inhalation uptake is large. In this group are common
      parabens, lower molecular weight phthalates, o-phenylphenol, Texanol, ethylene
      glycol, and alpha-terpineol. For other compounds, estimated dermal uptakes are
      small compared to inhalation. Examples include aliphatic hydrocarbons, single
      ring aromatics, terpenes, chlorinated solvents, formaldehyde, and acrolein.
      Analysis of published experimental data for human subjects for twenty different
      organic compounds substantiates these model predictions. However, transdermal
      uptake rates from air have not been measured for the indoor organics that have
      the largest modeled ratios of dermal-to-inhalation uptake; for such compounds,
      the estimates reported here require experimental verification. In accounting for
      total exposure to indoor organic pollutants and in assessing potential health
      consequences of such exposures, it is important to consider direct transdermal
      absorption from air. 

PMID- 24328317
TI  - Chromosome 18 transcriptoproteome of liver tissue and HepG2 cells and targeted
      proteome mapping in depleted plasma: update 2013.
AB  - We report the results obtained in 2012-2013 by the Russian Consortium for the
      Chromosome-centric Human Proteome Project (C-HPP). The main scope of this work
      was the transcriptome profiling of genes on human chromosome 18 (Chr 18), as well
      as their encoded proteome, from three types of biomaterials: liver tissue, the
      hepatocellular carcinoma-derived cell line HepG2, and blood plasma. The
      transcriptome profiling for liver tissue was independently performed using two
      RNaseq platforms (SOLiD and Illumina) and also by droplet digital PCR (ddPCR) and
      quantitative RT-PCR. The proteome profiling of Chr 18 was accomplished by
      quantitatively measuring protein copy numbers in the three types of biomaterial
      (the lowest protein concentration measured was 10(-13) M) using selected reaction
      monitoring (SRM). In total, protein copy numbers were estimated for 228 master
      proteins, including quantitative data on 164 proteins in plasma, 171 in the HepG2
      cell line, and 186 in liver tissue. Most proteins were present in plasma at 10(8)
      copies/MUL, while the median abundance was 10(4) and 10(5) protein copies per
      cell in HepG2 cells and liver tissue, respectively. In summary, for liver tissue
      and HepG2 cells a "transcriptoproteome" was produced that reflects the
      relationship between transcript and protein copy numbers of the genes on Chr 18.
      The quantitative data acquired by RNaseq, PCR, and SRM were uploaded into the
      "Update_2013" data set of our knowledgebase (www.kb18.ru) and investigated for
      linear correlations.

PMID- 24328318
TI  - One-step preparation of fluorographene: a highly efficient, low-cost, and large
      scale approach of exfoliating fluorographite.
AB  - Fluorographene, a cousin of graphene, not only inherits the excellent mechanical
      properties of graphene but also has great unique application potential in high
      performance devices and materials, such as lubricating agents, digital
      transistors, nanocomposites, and energy-storage devices. However, large-scale
      preparation of fluorographene remains a great challenge. Herein, an easy
      operating, highly scalable, and low-cost approach was reported for the
      preparation of fluorographene using commercially available fluorographite as the
      starting material. In this procedure, fluorographite turned into few-layer
      fluorographene through a rapid exfoliation process with Na2O2 and HSO3Cl as
      exfoliating agents. The whole preparation process was performed in air and
      without heating, sonication, and protective gas. The obtained fluorographene was
      characterized by Fourier transform infrared spectroscopy, Raman spectroscopy,
      (19)F nuclear magnetic resonance spectroscopy, X-ray diffraction,
      thermogravimetric analysis, atomic force microscopy, and transmission electron
      microscopy, and it possesses a hexagonal polycrystalline structure.
      Fluorographene and fluorographite were employed as cathode materials of the
      primary lithium battery, and it was found that the specific discharge capacity of
      the battery using fluorographene was improved remarkably compared to that using
      fluorographite. Cyclic voltammetry results also showed that specific capacitances
      of fluorographene were dozens of times higher than that of fluorographite. It is
      clear that electrochemical properties of fluorographene are significantly
      improved against fluorographite. 

PMID- 24328319
TI  - Antioxidant and tyrosinase inhibitory activities of flavonoids from Trifolium
      nigrescens Subsp. petrisavi.
AB  - Trifolium nigrescens was researched for its chemical constituents for the first
      time. Bioassay-guided isolation of the EtOAc extract from the leaves of T.
      nigrescens resulted in the purification of a new biflavone, 4''',5,5",7,7"
      pentahydroxy-3',3'''-dimethoxy-3-O-beta-d-glucosyl-3",4'-O-biflavone (1) along
      with eleven known compounds consisting of three phenolics (2-4), and eight
      flavonoid glycosides (5-12). Their structures were determined by extensive 1D and
      2D NMR, and MS data analyses. The isolated compounds were evaluated for their
      antioxidant activity and inhibitory activity on mushroom tyrosinase. Highly
      potent inhibitions were found by compounds 7 (IC50 = 0.38 mM), 8 (IC50 = 0.19
      mM), and 12 (IC50 = 0.26 mM) when compared with standard tyrosinase inhibitors
      kojic acid (IC50 = 0.67 mM) and l-mimosine (IC50 = 0.64 mM). The antioxidative
      effect of the isolated compounds and the extracts were determined by using beta
      carotene-linoleic acid, DPPH(*) scavenging, ABTS(+*) scavenging, superoxide
      scavenging, and CUPRAC assays. The experimental findings indicated that all the
      compounds demonstrated activity in all antioxidant activity tests employed except
      for the compounds 2-6. Compounds 2-6 showed moderate activity only in ABTS(+*)
      scavenging assay. The new compound 1 exhibited better activity than standard
      alpha-tocopherol in DPPH(*) scavenging, and ABTS(+*) scavenging assays. The
      results show that T. nigrescens can be regarded as a potential source of
      antioxidant compounds and tyrosinase inhibitors of significance in both the
      pharmaceutical and food industries. 

PMID- 24328320
TI  - Radio-frequency-transparent, electrically conductive graphene nanoribbon thin
      films as deicing heating layers.
AB  - Deicing heating layers are frequently used in covers of large radio-frequency
      (RF) equipment, such as radar, to remove ice that could damage the structures or
      make them unstable. Typically, the deicers are made using a metal framework and
      inorganic insulator; commercial resistive heating materials are often
      nontransparent to RF waves. The preparation of a sub-skin-depth thin film, whose
      thickness is very small relative to the RF skin (or penetration) depth, is the
      key to minimizing the RF absorption. The skin depth of typical metals is on the
      order of a micrometer at the gigahertz frequency range. As a result, it is very
      difficult for conventional conductive materials (such as metals) to form large
      area sub-skin-depth films. In this report, we disclose a new deicing heating
      layer composite made using graphene nanoribbons (GNRs). We demonstrate that the
      GNR film is thin enough to permit RF transmission. This metal-free, ultralight,
      robust, and scalable graphene-based RF-transparent conductive coating could
      significantly reduce the size and cost of deicing coatings for RF equipment
      covers. This is important in many aviation and marine applications. This is a
      demonstration of the efficacy and applicability of GNRs to afford performances
      unattainable by conventional materials. 

PMID- 24328321
TI  - Cellulose nanocrystal-mediated synthesis of silver nanoparticles: role of sulfate
      groups in nucleation phenomena.
AB  - Developing sustainable chemical methods to synthesize silver nanoparticles has
      drawn significant research interest. Due to their unique and well-defined
      physical-chemical properties, cellulose nanocrystals (CNCs) have become one of
      the most promising renewable nanomaterials. Here we use CNC to mediate silver
      nanoparticle synthesis and elucidate the effect of CNC surface chemistry (as
      defined by sulfate groups) in nanoparticle formation and nucleation in the
      presence of borohydride reduction. Pristine CNCs produced by sulfuric acid
      hydrolysis and partially desulfated CNCs mediated the formation of silver
      nanoparticles of different sizes (and size distribution) following different
      rates of formation, as determined by transmission electron microscopy (TEM) and
      UV-vis spectroscopy. The results shed light on methods to stabilize silver
      nanoparticles, control their nucleation, and highlight the potential of CNCs in
      metal nanoparticle synthesis. 

PMID- 24328322
TI  - Monitoring cellular uptake and cytotoxicity of copper(II) complex using a
      fluorescent anthracene thiosemicarbazone ligand.
AB  - The thiosemicarbazone derivative of anthracene (ATSC, anthracene
      thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and
      characterized by spectroscopic, electrochemical, and crystallographic techniques.
      Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption
      and emission spectral methods, and viscosity measurements reveal a partial
      intercalation binding mode. Their protein binding ability was monitored by the
      quenching of tryptophan emission using bovine serum albumin (BSA) as a model
      protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the
      HeLa cell line, and flow cytometric analysis were carried out to ascertain the
      mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle
      arrest in sub-G1 phase. 

PMID- 24328323
TI  - Strategies for replicating anatomical cartilaginous tissue gradient in engineered
      intervertebral disc.
AB  - A critical challenge in fabricating a load bearing tissue, such as an
      intervertebral disc, is to simulate cellular and matrix alignment and anisotropy,
      as well as a specific biochemical gradient. Towards this goal, multilamellar silk
      fibroin scaffolds having criss-cross fibrous orientation were developed, where
      silk fibers in inner layers were crosslinked with bioactive molecule chondroitin
      sulfate. Upon culturing goat articular chondrocytes under static and dynamic
      conditions, lamellar scaffold architecture guided alignment of cells and the
      newly synthesized extracellular matrix (ECM) along the silk fibers. The dynamic
      culture conditions further improved the cellular metabolic rate and ECM
      production. Further the synergistic effect of chemical composition of scaffold
      and hydrodynamic environment of bioreactor contributed in developing a tissue
      gradient within the constructs, with an inner region rich in collagen II,
      glycosaminoglycan (GAG), and stiffer in compression, whereas an outer region rich
      in collagen I and stiffer in tension. Therefore, a unique combination of chemical
      and physical parameters of engineered constructs and dynamic culture conditions
      provides a promising starting point to further improve the system towards
      replicating the anatomical structure, composition gradient, and function of
      intervertebral disc tissue. 

PMID- 24328324
TI  - Synthesis and characterization of the crystal and magnetic structures and
      properties of the hydroxyfluorides Fe(OH)F and Co(OH)F.
AB  - The title compounds were synthesized by a hydrothermal route from a 1:1 molar
      ratio of lithium fluoride and transition-metal acetate in an excess of water. The
      crystal structures were determined using a combination of powder and/or single
      crystal X-ray and neutron powder diffraction (NPD) measurements. The magnetic
      structure and properties of Co(OH)F were characterized by magnetic susceptibility
      and low-temperature NPD measurements. M(OH)F (M = Fe and Co) crystallizes with
      structures related to diaspore-type alpha-AlOOH, with the Pnma space group, Z =
      4, a = 10.471(3) A, b = 3.2059(10) A, and c = 4.6977(14) A and a = 10.2753(3) A,
      b = 3.11813(7) A, and c = 4.68437(14) A for the iron and cobalt phases,
      respectively. The structures consist of double chains of edge-sharing M(F,O)6
      octahedra running along the b axis. These infinite chains share corners and give
      rise to channels. The protons are located in the channels and form O-H...F bent
      hydrogen bonds. The magnetic susceptibility indicates an antiferromagnetic
      ordering at ~40 K, and the NPD measurements at 3 K show that the ferromagnetic
      rutile-type chains with spins parallel to the short b axis are
      antiferromagnetically coupled to each other, similarly to the magnetic structure
      of goethite alpha-FeOOH. 

PMID- 24328325
TI  - Reaction of a bridged frustrated Lewis pair with nitric oxide: a kinetics study.
AB  - Described is a kinetics and computational study of the reaction of NO with the
      intramolecular bridged P/B frustrated Lewis pair (FLP) endo-2
      (dimesitylphosphino)-exo-3-bis(pentafluorophenyl)boryl-norbornane to give a
      persistent FLP-NO aminoxyl radical. This reaction follows a second-order rate
      law, first-order in [FLP] and first-order in [NO], and is markedly faster in
      toluene than in dichloromethane. By contrast, the NO oxidation of the phosphine
      base 2-(dimesitylphosphino)norbornene to the corresponding phosphine oxide
      follows a third-order rate law, first-order in [phosphine] and second-order in
      [NO]. Formation of the FLP-NO radical in toluene occurs with a DeltaH(?) of 13
      kcal mol(-1), a feature that conflicts with the computation-based conclusion that
      NO addition to a properly oriented B/P pair should be nearly barrierless. Since
      the calculations show the B/P pair in the most stable solution structure of this
      FLP to have an unfavorable orientation for concerted reaction, the observed
      barrier is rationalized in terms of the reversible formation of a [B]-NO complex
      intermediate followed by a slower isomerization-ring closure step to the cyclic
      aminoxyl radical. This combined kinetics/theoretical study for the first time
      provides insight into mechanistic details for the activation of a diatomic
      molecule by a prototypical FLP.

PMID- 24328326
TI  - Simple nanoparticle-based luminometric method for molecular weight determination
      of polymeric compounds.
AB  - A nanoparticle-based method utilizing time-resolved luminescence resonance energy
      transfer (TR-LRET) was developed for molecular weight determination. This mix-and
      measure nanoparticle method is based on the competitive adsorption between the
      analyte and the acceptor-labeled protein to donor Eu(III) nanoparticles. The size
      dependent adsorption of molecules enables the molecular weight determination of
      differently sized polymeric compounds down to a concentration level of micrograms
      per liter. The molecular weight determination from 1 to 10 kDa for polyamino
      acids and from 0.3 to 70 kDa for polyethylene imines is demonstrated. The simple
      and cost-effective nanoparticle method as microtiter plate assay format shows
      great potential for the detection of the changes in molecular weight or for
      quantification of differently sized molecules in biochemical laboratories and in
      industrial polymeric processes. 

PMID- 24328327
TI  - Out of equilibrium divergence of dissipation in an oscillating bubble coated by
      surfactants.
AB  - We report measurements of the relaxation and resonance frequency of forced
      oscillating bubbles covered by a layer of surface-active molecules, the anionic
      surfactant sodium dodecyl sulfate (SDS). Less systematic investigations have been
      also carried out on neutral and cationic surfactants. A divergence of the viscous
      damping is observed at a very low bulk concentration. Subtle variations in the
      resonance peak are also measured. Bubble oscillations are driven by an electric
      field and measured with a sensitive interferometric technique. Results are
      interpreted with a model which takes care of the coupling between the dynamics of
      fluid surface oscillations and the properties of a surfactant monolayer in the
      vicinity of the phase transition from a gas-like distribution to a liquid-like
      assembly (the so-called gas-LE transition). Important charge effects are also
      considered. The basic assumptions of the model (cooperative adsorption of the
      surfactant at the air-water interface and coupling between the shape of the
      deformed surface and the local surfactant concentration) have been fully
      confirmed by extensive coarse-grained molecular dynamics simulations on model
      systems. 

PMID- 24328328
TI  - Size-controlled vaterite composite particles with a POSS-core dendrimer for the
      fabrication of calcite thin films by phase transition.
AB  - Vaterite composite particles with a size-controlled sphere were obtained by a
      carbonate controlled-addition method by using a carboxylate-terminated
      poly(amidoamine) (PAMAM)-type polyhedral oligomeric silsesquioxane (POSS)-core
      dendrimer. An aqueous ammonium carbonate solution was added to an aqueous
      solution of the dendrimer and CaCl2 at different times (3 min, 30 min, and 1 h)
      and stirred for 1 h at 30  degrees C. When the complexation time of the POSS-core
      dendrimer-CaCl2 solution was increased from 3 min to 1 h, the average particle
      sizes of the spheres increased from 0.71 +/- 0.08 to 1.86 +/- 0.22 MUm,
      respectively. However, the average particle sizes decreased with decreasing
      temperature. Particles with minimum sizes of 70 +/- 6 nm were obtained when COONa
      to calcium ion molar ratio was 16 and the complexation time was 3 min at 20 
      degrees C. Incubation of the vaterite composite particles in distilled water for
      3 days led to complete phase transition to calcite. Negative zeta potential
      values, ranging from -30 to -10 mV, were detected for the vaterite particles,
      indicating that the POSS-core dendrimers were exposed on the CaCO3 particles. The
      CaCO3 particle surfaces were successfully coated with
      poly(diallyldimethylammonium chloride) (PDDA) in aqueous dispersions by adding a
      controlled concentration of the polymer. Alternate vaterite composite particles
      and polyelectroyte multilayer films were prepared by a layer-by-layer method. The
      obtained (PDDA/vaterite)10(PDDA) multilayer films were incubated in distilled
      water at 30  degrees C. Incubation for 5 days led to complete phase transition to
      calcite, as estimated by Fourier transform infrared (FTIR) spectroscopic and XRD
      analyses. The SEM observation of the sample after 5 days of incubation showed a
      granular network structure of irregularly shaped calcite particles. Although some
      patches and pores were present in the films, the SEM image clearly demonstrated
      that large-area and continuous CaCO3 films were formed. 

PMID- 24328329
TI  - Large-area synthesis of highly crystalline WSe(2) monolayers and device
      applications.
AB  - The monolayer transition metal dichalcogenides have recently attracted much
      attention owing to their potential in valleytronics, flexible and low-power
      electronics, and optoelectronic devices. Recent reports have demonstrated the
      growth of large-size two-dimensional MoS2 layers by the sulfurization of
      molybdenum oxides. However, the growth of a transition metal selenide monolayer
      has still been a challenge. Here we report that the introduction of hydrogen in
      the reaction chamber helps to activate the selenization of WO3, where large-size
      WSe2 monolayer flakes or thin films can be successfully grown. The top-gated
      field-effect transistors based on WSe2 monolayers using ionic gels as the
      dielectrics exhibit ambipolar characteristics, where the hole and electron
      mobility values are up to 90 and 7 cm(2)/Vs, respectively. These films can be
      transferred onto arbitrary substrates, which may inspire research efforts to
      explore their properties and applications. The resistor-loaded inverter based on
      a WSe2 film, with a gain of ~13, further demonstrates its applicability for logic
      circuit integrations. 

PMID- 24328330
TI  - Spatial arrangement of organic compounds on a model mineral surface: implications
      for soil organic matter stabilization.
AB  - The complexity of the mineral-organic carbon interface may influence the extent
      of stabilization of organic carbon compounds in soils, which is important for
      global climate futures. The nanoscale structure of a model interface was examined
      here by depositing films of organic carbon compounds of contrasting chemical
      character, hydrophilic glucose and amphiphilic stearic acid, onto a soil mineral
      analogue (Al2O3). Neutron reflectometry, a technique which provides depth
      sensitive insight into the organization of the thin films, indicates that glucose
      molecules reside in a layer between Al2O3 and stearic acid, a result that was
      verified by water contact angle measurements. Molecular dynamics simulations
      reveal the thermodynamic driving force behind glucose partitioning on the mineral
      interface: The entropic penalty of confining the less mobile glucose on the
      mineral surface is lower than for stearic acid. The fundamental information
      obtained here helps rationalize how complex arrangements of organic carbon on
      soil mineral surfaces may arise. 

PMID- 24328331
TI  - Minor groove binding of the food colorant carmoisine to DNA: spectroscopic and
      calorimetric characterization studies.
AB  - The interaction of the food additive carmoisine with herring testes DNA was
      studied by multifaceted biophysical techniques. Carmoisine exhibited hypochromic
      effects in absorbance, whereas in fluorescence the intensity enhanced upon
      complexation with DNA. Energy transfer from the DNA base pairs to carmoisine
      molecules occurred upon complexation. A groove binding model of interaction was
      envisaged for carmoisine-DNA complexation from 4',6-diamidino-2-phenylindole
      (DAPI) and Hoechst displacement studies. The binding of carmoisine stabilized the
      DNA structure against thermal denaturation. The binding induced moderate
      conformational perturbations in the B-form structure of DNA. The binding affinity
      (10(4) M(-1)) values, calculated from absorbance and fluorescence data, and
      calorimetry titrations were in close agreement with each other. The binding was
      characterized to be exothermic and favored by small negative enthalpic and large
      positive entropic contributions. Salt-dependent calorimetric studies revealed
      that the binding reaction was dominated by nonpolyelectrolytic forces. The
      negative heat capacity value suggested the role of hydrophobic effect in the
      interaction. 

PMID- 24328332
TI  - Reaction analysis for deprotonation of the sulfonic group of perfluorosulfonic
      acid molecules at low hydration levels.
AB  - A reaction analysis for deprotonation of the sulfonic group in a model molecule
      of perfluorosulfonic acid (PFSA) at low hydration levels was performed. PFSA is
      usually adopted as a polymer electrolyte membrane in polymer electrolyte fuel
      cells. In hydration level three, the deprotonation reaction certainly occurs. The
      deprotonated state produced is more stable than the predeprotonated state by 3.72
      kcal/mol. In addition, its activation energy is very low. Although quantitative
      discussion of this activation energy is difficult considering the computational
      error, it can be said qualitatively that H(+) is abstracted smoothly from the
      sulfonic group because of a low activation energy. From the results of bond-order
      analysis, the produced H3O(+) is strongly bound by the SO3(-) group. Thus,
      diffusivity of H3O(+) would be low. In hydration level four or more, we found a
      possibility that the diffusivity of H3O(+) increases because the hydrogen-bond
      strength between H3O(+) and SO3(-) is lower or SO3(-) cannot bind H3O(+) directly
      by forming an Eigen cation. 

PMID- 24328333
TI  - Palladium/single-walled carbon nanotube back-to-back Schottky contact-based
      hydrogen sensors and their sensing mechanism.
AB  - A Schottky contact-based hydrogen (H2) gas sensor operable at room temperature
      was constructed by assembling single-walled carbon nanotubes (SWNTs) on a Si/SiO2
      substrate bridged by Pd microelectrodes in a chemiresistive/chemical field effect
      transistor (chemFET) configuration. The Schottky barrier (SB) is formed by
      exposing the Pd-SWNT interfacial contacts to H2 gas, the analyte it was designed
      to detect. Because a Schottky barrier height (SBH) acts as an exponential
      bottleneck to current flow, the electrical response of the sensor can be
      particularly sensitive to small changes in SBH, yielding an enhanced response to
      H2 gas. The sensing mechanism was analyzed by I-V and FET properties before and
      during H2 exposure. I-Vsd characteristics clearly displayed an equivalent back-to
      back Schottky diode configuration and demonstrated the formation of a SB during
      H2 exposure. The I-Vg characteristics revealed a decrease in the carrier mobility
      without a change in carrier concentration; thus, it corroborates that modulation
      of a SB via H2 adsorption at the Pd-SWNT interface is the main sensing mechanism.

PMID- 24328334
TI  - Response to comment on "cancer risk from incidental ingestion exposures to PAHs
      associated with coal-tar-sealed pavement".

PMID- 24328335
TI  - Molecular mechanisms for the reaction between ()OH radicals and proline: insights
      on the role as reactive oxygen species scavenger in plant stress.
AB  - The accumulation of proline (Pro) and overproduction of reactive oxygen species
      (ROS) by plants exposed to stress is well-documented. In vitro assays show that
      enzyme inactivation by hydroxyl radicals ((*)OH) can be avoided in the presence
      of Pro, suggesting this amino acid might act as a (*)OH scavenger. Although
      production of hydroxyproline (Hyp) has been hypothesized in connection with such
      antioxidant activity, no evidence on the detailed mechanism of scavenging has
      been reported. To elucidate whether and how Hyp might be produced, we used
      density functional theory calculations coupled to a polarizable continuum model
      to explore 27 reaction channels including H-abstraction by (*)OH and (*)OH/H2O
      addition. The structure and energetics of stable species and transition states
      for each reaction channel were characterized at the PCM-(U)M06/6-31G(d,p) level
      in aqueous solution. Evidence is found for a main pathway in which Pro scavenges
      (*)OH by successive H-abstractions (DeltaG(?,298) = 4.1 and 7.5 kcal mol(-1)) to
      yield 3,4-Delta-Pro. A companion pathway with low barriers yielding Delta(1)
      pyrroline-5-carboxylate (P5C) is also supported, linking with 5-Hyp through
      hydration. However, this connection remains unlikely in stressed plants because
      P5C would be efficiently recycled to Pro (contributing to its accumulation) by
      P5C reductase, hypothesis coined here as the "Pro-Pro cycle".

PMID- 24328336
TI  - Variation of protein corona composition of gold nanoparticles following plasmonic
      heating.
AB  - It is well recognized that the primary interaction of most biological
      environments with nanoparticles (NPs) is strongly influenced by a long-lived
      ("hard") protein corona that surrounds the NP and remains strongly adsorbed to
      its surface. The amount and composition of associated proteins in the corona
      adsorbed onto the NPs is related to several important factors, including the
      physicochemical properties of the NPs and the composition of the protein
      solution. Here, for the first time, it is shown that plasmonic heat induction (by
      laser activation) leads to significant changes in the composition of the hard
      protein corona adsorbed on low aspect ratio gold nanorods. Using mass
      spectrometry, several proteins in the corona were identified whose concentrations
      change most substantially as a result of photoinduced (plasmonic) heating versus
      simple thermal heating. Molecular modeling suggests that the origin of these
      changes in protein adsorption may be the result of protein conformational changes
      in response to much higher local temperatures that occur near the gold nanorods
      during photoinduced, plasmonic heating. These results may define new applications
      in vivo for NPs with hyperthermia capability and better define the likely
      interactions of cells with NPs after plasmonic heating. Potential changes in the
      protein corona following hyperthermia treatment may influence the final
      biological fate of plasmonic NPs in clinical applications and help elucidate
      safety considerations for hyperthermia applications. 

PMID- 24328337
TI  - Optimizing electron transfer mediators based on arylimidazoles by ring fusion:
      synthesis, electrochemistry, and computational analysis of 2-aryl-1
      methylphenanthro[9,10-d]imidazoles.
AB  - A significant improvement of the properties of redox catalysts based on the
      triarylimidazole framework can be achieved with a simple structural modification.
      By linking the ortho-carbons of the aromatics positioned at C-4 and C-5, a fused
      framework is generated, removing the distortion from planarity and enhancing the
      influence of the substituents on the redox properties. This modification leads
      not only to a much broader range of available redox potentials for the resulting
      phenanthro[9,10-d]imidazoles but also to improved stability of the corresponding
      radical cation. These concepts were verified with eight new phenanthro[9,10
      d]imidazole derivatives, using cyclic voltammetry and DFT calculations. For this
      purpose, an optimized and general synthetic route to the desired compounds was
      developed. An excellent linear correlation of the calculated effective ionization
      potentials with the experimental oxidation potentials was obtained, allowing for
      an accurate prediction of oxidation potentials of derivatives yet to be
      synthesized. Moreover, high catalytic activity was found for electro-oxidative C
      H activation reactions. 

PMID- 24328338
TI  - Shape- and symmetry-dependent mechanical properties of metallic gold and silver
      on the nanoscale.
AB  - The mechanical properties of anisotropic nanoparticles like gold nanorods (AuNRs)
      and silver nanorods (AgNRs) are different from those of isotropic shapes such as
      nanospheres. We probed the coherent lattice oscillations of nanoparticles by
      following the modulation of the plasmonic band frequency using ultrafast laser
      spectroscopy. We found that while the frequency of the longitudinal vibration
      mode of AgNRs is higher than that of AuNRs of similar dimensions, similarly sized
      gold and silver nanospheres have similar lattice vibration frequencies. Lattice
      vibrations calculated by finite element modeling showed good agreement with the
      experimental results for both AgNRs and AuNRs. The accuracy of the calculations
      was improved by using actual pentagonal shapes rather than cylinders that did not
      agree well with the experimental results. As the plasmon energy is transferred
      into lattice vibrations, the temperature of the nanoparticle necessarily
      increases as a result of this electron-phonon relaxation process. This results in
      a decrease in the Young's modulus that was accounted for in the calculations.
      Calculations showed that the tips of the nanorods are "softer" than the rest of
      the nanorod. Because the tips comprise a larger portion of the overall rod in the
      smaller rods, the smaller rods were more affected by the tip effects. 

PMID- 24328339
TI  - Multicomponent-multicatalyst reactions (MC)(2)R: efficient dibenzazepine
      synthesis.
AB  - A Rh(I)/Pd(0) catalyst system was applied to the multicomponent synthesis of aza
      dibenzazepines from vinylpyridines, arylboronic acids, and amines in a domino
      process with no intermediate isolation or purification. 

PMID- 24328340
TI  - Role of oxygen in the regulation of Leydig tumor derived MA-10 cell steroid
      production: the effect of cobalt chloride.
AB  - We have earlier shown that cobalt chloride (CoCl2)-induced hypoxia and second
      messenger 8-bromoadenosine 3', 5'-cyclic adenosine monophosphate (8-Br-cAMP)
      stimulates vascular endothelial growth factor (VEGF) production in Leydig tumor
      cell derived MA-10 cells. Both stimuli follow common signal transduction pathways
      including protein kinase A (PK-A), extracellular regulated kinase 1/2 (ERK1/2),
      and phosphatidyl inositol-3 kinase/akt (PI3-K/Akt) pathways in the stimulation of
      VEGF by MA-10 cells. In the present study we investigated the role of CoCl2 and 8
      Br-cAMP on steroid production in MA-10 cells. The MA-10 cells were cultured in
      Waymouth MB 752/1 medium, supplemented with 15% heat inactivated horse serum.
      Progesterone was estimated by radioimmunoassay (RIA).We report that 8-Br-cAMP
      stimulated progesterone production by the MA-10 cells whereas CoCl2 inhibited the
      same. Also, 8-Br-cAMP stimulated steroidogenic acute regulatory protein (StAR)
      and cytochrome P450 side-chain cleavage enzyme (P450scc) mRNAs expression.
      However, CoCl2 had no effect on StAR mRNA. Cobalt chloride directly inhibited the
      expression of P450scc mRNA. The decrease in progesterone production could be
      attributed to three different mechanisms, (1) an increase in production of
      reactive oxygen species (ROS), (2) an increase in HIF-1alpha activity, and (3)
      ultimately a decrease in the level of cytochrome P450 side chain cleavage (CYT
      P450scc). Hypoxia has an action and mechanism of action similar to that of
      gonadotropins on VEGF production, whereas they have a contrasting effect on
      steroidogenesis. This study suggests that hypoxia could be as important as
      gonadotropins in regulating Leydig cell steroidogenesis.

PMID- 24328341
TI  - Tackling lipophilicity of peptide drugs: replacement of the backbone N-methyl
      group of cilengitide by N-oligoethylene glycol (N-OEG) chains.
AB  - Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was was developed
      as a highly active and selective ligand for the alphavbeta3 and alphavbeta5
      integrin receptors. We describe the synthesis of three analogues of this peptide
      in which the N-Me group has been replaced by N-oligoethylene glycol (N-OEG)
      chains of increasing size: namely N-OEG2, N-OEG11, and N-OEG23, which are
      respectively composed of 2, 11, and 23 ethylene oxide monomer units. The
      different N-OEG cyclopeptides and the original peptide were compared with respect
      to lipophilicity and biological activity. The N-OEG2 analogue was straightforward
      to synthesize in solid phase using an Fmoc-N-OEG2 building block. The syntheses
      of the N-OEG11 and N-OEG23 cyclopeptides are hampered by the increased steric
      hindrance of the N-substituent, and could only be achieved by segment coupling,
      which takes place with epimerization and thus requires extensive product
      purification. All the N-OEG analogues were found to be more hydrophobic than the
      parent peptide, and their hydrophobicity was systematically enhanced upon
      increasing the length of the OEG chain. The N-OEG2 cyclopeptide displayed the
      same capacity as Cilengitide to inhibit the integrin-mediated adhesion of HUVEC
      endothelial, DAOY gliobastoma, and HT-29 colon cancer cells to their ligands
      vitronectin and fibrinogen. The N-OEG11 and N-OEG23 analogues also inhibited cell
      adhesion to these immobilized ligands, but their IC50 values dropped by 1 order
      of magnitude with respect to the parent peptide. These results indicate that
      replacement of the backbone N-Me group of Cilengitide by a short N-OEG chain
      provides a more lipophilic analogue with a similar biological activity. Upon
      increasing the size of the N-OEG chain, liophilicity is enhanced, but synthetic
      yields drop and the longer polymer chains may impede targeted binding. 

PMID- 24328342
TI  - Investigating catalase activity through hydrogen peroxide decomposition by
      bacteria biofilms in real time using scanning electrochemical microscopy.
AB  - Catalase activity through hydrogen peroxide decomposition in a 1 mM bulk solution
      above Vibrio fischeri (gamma-Protebacteria-Vibrionaceae) bacterial biofilms of
      either symbiotic or free-living strains was studied in real time by scanning
      electrochemical microscopy (SECM). The catalase activity, in units of micromoles
      hydrogen peroxide decomposed per minute over a period of 348 s, was found to vary
      with incubation time of each biofilm in correlation with the corresponding growth
      curve of bacteria in liquid culture. Average catalase activity for the same
      incubation times ranging from 1 to 12 h was found to be 0.28 +/- 0.07 MUmol
      H2O2/min for the symbiotic biofilms and 0.31 +/- 0.07 MUmol H2O2/min for the free
      living biofilms, suggesting similar catalase activity. Calculations based on
      Comsol Multiphysics simulations in fitting experimental biofilm data indicated
      that approximately (3 +/- 1) * 10(6) molecules of hydrogen peroxide were
      decomposed by a single bacterium per second, signifying the presence of a highly
      active catalase. A 2-fold enhancement in catalase activity was found for both
      free-living and symbiotic biofilms in response to external hydrogen peroxide
      concentrations as low as 1 nM in the growth media, implying a similar mechanism
      in responding to oxidative stress. 

PMID- 24328343
TI  - AgCu3V4O12: a novel perovskite containing mixed-valence silver ions.
AB  - A novel silver-containing perovskite, AgCu3V4O12, was synthesized under high
      pressure and high-temperature conditions. It crystallizes in an A-site-ordered
      perovskite structure (space group Im3), in which silver ions occupy the 12
      coordinated A sites forming regular icosahedra, and exhibits metallic behavior.
      Bond-valence-sum calculations and X-ray photoemission spectroscopy reveal that Ag
      ions are present in the mixed-valence state, most likely attributable to the
      coexistence of Ag(+) and Ag(3+), unlike the case of well-known perovskite-type
      AgNbO3 and AgTaO3 containing only Ag(+) ions. We discuss metallic conduction in
      relation to electronic structure calculations.

PMID- 24328345
TI  - Theoretical 57Fe Mossbauer spectroscopy for structure elucidation of [Fe]
      hydrogenase active site intermediates.
AB  - [Fe] hydrogenase is a hydrogen activating enzyme that features a monoiron active
      site, which can be well characterized by Mossbauer spectroscopy. Mossbauer
      spectra have been measured of the CO and CN(-) inhibited species as well as under
      turnover conditions [Shima, S. et al., J. Am. Chem. Soc., 2005, 127, 10430]. This
      study presents calculated Mossbauer parameters for various active-site models of
      [Fe] hydrogenase to provide structural information about the species observed in
      experiment. Because theoretical Mossbauer spectroscopy requires the
      parametrization of observables from first-principles calculations (i.e., electric
      field gradients and contact densities) to the experimental observables (i.e.,
      quadrupole splittings and isomer shifts), nonrelativistic and relativistic
      density functional theory methods are parametrized against a reference set of Fe
      complexes specifically selected for the application to the Fe center in [Fe]
      hydrogenase. With this methodology, the measured parameters for the CO and CN(-)
      inhibited complexes can be reproduced. Evidence for the protonation states of the
      hydroxyl group in close proximity to the active site and for the thiolate ligand,
      which could participate in proton transfer, is obtained. The unknown resting
      state measured in the presence of the substrate and under pure H2 atmosphere is
      identified to be a water-coordinated complex. Consistent with previous
      assignments based on infrared and X-ray absorption near-edge spectroscopy, all
      measured Mossbauer data can be reproduced with the active site's iron atom being
      in oxidation state +2.

PMID- 24328346
TI  - Low-contact-resistance graphene devices with nickel-etched-graphene contacts.
AB  - The performance of graphene-based transistors is often limited by the large
      electrical resistance across the metal-graphene contact. We report an approach to
      achieve ultralow resistance metal contacts to graphene transistors. Through a
      process of metal-catalyzed etching in hydrogen, multiple nanosized pits with
      zigzag edges are created in the graphene portions under source/drain metal
      contacts while the graphene channel remains intact. The porous graphene
      source/drain portions with pure zigzag-termination form strong chemical bonds
      with the deposited nickel metallization without the need for further annealing.
      This facile contact treatment prior to electrode metallization results in contact
      resistance as low as 100 Omega.MUm in single-layer graphene field-effect
      transistors, and 11 Omega.MUm in bilayer graphene transistors. Besides 96%
      reduction in contact resistance, the contact-treated graphene transistors exhibit
      1.5-fold improvement in mobility. More importantly, the metal-catalyzed etching
      contact treatment is compatible with complementary metal-oxide-semiconductor
      (CMOS) fabrication processes, and holds great promise to meet the contact
      performance required for the integration of graphene in future integrated
      circuits. 

PMID- 24328344
TI  - Synthetic cluster models of biological and heterogeneous manganese catalysts for
      O2 evolution.
AB  - Artificial photosynthesis has emerged as an important strategy toward clean and
      renewable fuels. Catalytic oxidation of water to O2 remains a significant
      challenge in this context. A mechanistic understanding of currently known
      heterogeneous and biological catalysts at a molecular level is highly desirable
      for fundamental reasons as well as for the rational design of practical
      catalysts. This Award Article discusses recent efforts in synthesizing structural
      models of the oxygen-evolving complex of photosystem II. These structural motifs
      are also related to heterogeneous mixed-metal oxide catalysts. A stepwise
      synthetic methodology was developed toward achieving the structural complexity of
      the targeted active sites. A geometrically restricted multinucleating ligand, but
      with labile coordination modes, was employed for the synthesis of low-oxidation
      state trimetallic species. These precursors were elaborated to site
      differentiated tetrametallic complexes in high oxidation states. This methodology
      has allowed for structure-reactivity studies that have offered insight into the
      effects of different components of the clusters. Mechanistic aspects of oxygen
      atom transfer and incorporation from water have been interrogated. Significantly,
      a large and systematic effect of redox-inactive metals on the redox properties of
      these clusters was discovered. With the pKa value of the redox-inactive metal
      aqua complex as a measure of the Lewis acidity, structurally analogous clusters
      display a linear dependence between the reduction potential and acidity; each pKa
      unit shifts the potential by ca. 90 mV. Implications for the function of the
      biological and heterogeneous catalysts are discussed. 

PMID- 24328347
TI  - DNA-modified electrodes fabricated using copper-free click chemistry for enhanced
      protein detection.
AB  - A method of DNA monolayer formation has been developed using copper-free click
      chemistry that yields enhanced surface homogeneity and enables variation in the
      amount of DNA assembled; extremely low-density DNA monolayers, with as little as
      5% of the monolayer being DNA, have been formed. These DNA-modified electrodes
      (DMEs) were characterized visually, with AFM, and electrochemically, and were
      found to facilitate DNA-mediated reduction of a distally bound redox probe. These
      low-density monolayers were found to be more homogeneous than traditional thiol
      modified DNA monolayers, with greater helix accessibility through an increased
      surface area-to-volume ratio. Protein binding efficiency of the transcriptional
      activator TATA-binding protein (TBP) was also investigated on these surfaces and
      compared to that on DNA monolayers formed with standard thiol-modified DNA. Our
      low-density monolayers were found to be extremely sensitive to TBP binding, with
      a signal decrease in excess of 75% for 150 nM protein. This protein was
      detectable at 4 nM, on the order of its dissociation constant, with our low
      density monolayers. The improved DNA helix accessibility and sensitivity of our
      low-density DNA monolayers to TBP binding reflects the general utility of this
      method of DNA monolayer formation for DNA-based electrochemical sensor
      development. 

PMID- 24328348
TI  - Microbial extracellular polymeric substances reduce Ag+ to silver nanoparticles
      and antagonize bactericidal activity.
AB  - Whereas the antimicrobial mechanisms of silver have been extensively studied and
      exploited for numerous applications, little is known about the associated
      bacterial adaptation and defense mechanisms that could hinder disinfection
      efficacy or mitigate unintended impacts to microbial ecosystem services
      associated with silver release to the environment. Here, we demonstrate that
      extracellular polymeric substances (EPS) produced by bacteria constitute a
      permeability barrier with reducing constituents that mitigate the antibacterial
      activity of silver ions (Ag(+)). Specifically, manipulation of EPS in Escherichia
      coli suspensions (e.g., removal of EPS attached to cells by
      sonication/centrifugation or addition of EPS at 200 mg L(-1)) demonstrated its
      critical role in hindering intracellular silver penetration and enhancing cell
      growth in the presence of Ag(+) (up to 0.19 mg L(-1)). High-resolution
      transmission electron microscopy (HRTEM) combined with X-ray photoelectron
      spectroscopy (XPS) and energy-dispersive spectrometry (EDS) analyses showed that
      Ag(+) was reduced to silver nanoparticles (AgNPs; 10-30 nm in diameter) that were
      immobilized within the EPS matrix. Fourier transform infrared (FTIR) and (13)C
      nuclear magnetic resonance (NMR) spectra suggest that Ag(+) reduction to AgNPs by
      the hemiacetal groups of sugars in EPS contributed to immobilization.
      Accordingly, the amount and composition of EPS produced have important
      implications on the bactericidal efficacy and potential environmental impacts of
      Ag(+). 

PMID- 24328349
TI  - Perceived reasons for, opinions about, and suggestions for elders considering
      suicide: elderly outpatients' perspectives.
AB  - OBJECTIVES: The purposes of this study were to explore elderly outpatients'
      perceived reasons for, opinions of, and suggestions for elderly people
      considering suicide in Taiwan. METHOD: Elderly outpatients (N = 83) were
      recruited in 2011-2012 by convenience sampling from three randomly selected
      medical centers in Taiwan. Data were collected in individual interviews using a
      semi-structured guide and analyzed by content analysis. RESULTS: Findings
      revealed that most participants had heard of elderly suicide, with television
      news as the main source for their information. Their opinions about elderly
      suicide reflected judgmental attitudes, negative emotional reactions,
      expectations of social welfare, and could happen after losing one's meaning in
      life. Their suggestions for elderly people considering suicide fell into four
      major themes: give up suicidal ideas, seek help, enhance social welfare, and
      attend religious activities. CONCLUSION: Since television news was the main
      source for participants' information about elderly suicide, this mass medium
      should be used in suicide prevention to disseminate suicide knowledge, increase
      access to help, and strengthen suicide-protective factors among the elderly.
      Furthermore, no participants mentioned depression as a reason for attempted or
      completed suicide among older people despite depression being a well-known
      suicide-risk factor. Future suicide-prevention programs should emphasize the role
      of depression in suicide among older people. Participants also did not suggest
      that older people considering suicide seek help from the health system. Thus,
      older people should be educated about the role of the health system in suicide
      prevention and trained as gatekeepers to recognize signs of suicide ideation and
      respond appropriately.

PMID- 24328350
TI  - Substrate stereocontrol in the intramolecular organocatalyzed Tsuji-Trost
      reaction: enantioselective synthesis of allokainates.
AB  - Organocatalyzed Tsuji-Trost cyclization of 3b proceeds with asymmetric induction
      and allows for stereoselective synthesis of (+)-allokainic acid. The
      stereochemical outcome of the cyclization was predicted by calculations. 

PMID- 24328351
TI  - Multifunctional silicon surfaces: reaction of dichlorocarbene generated from
      Seyferth reagent with hydrogen-terminated silicon (111) surfaces.
AB  - Insertion of dichlorocarbene (:CCl2), generated by decomposition of the Seyferth
      reagent PhHgCCl2Br, into the Si-H bond of a tertiary silane to form a Si-CCl2H
      group is an efficient homogeneous, molecular transformation. A heterogeneous
      version of this reaction, between PhHgCCl2Br and a silicon (111) surface
      terminated by tertiary Si-H bonds, was studied using a combination of surface
      sensitive infrared and X-ray photoelectron spectroscopies. The insertion of
      dichlorocarbene into surface Si-H bonds parallels the corresponding reaction of
      silanes in solution, to produce surface-bound dichloromethyl groups (Si-CCl2H)
      covering ~25% of the silicon surface sites. A significant fraction of the
      remaining Si-H bonds on the surface was converted to Si-Cl/Br groups during the
      same reaction, with PhHgCCl2Br serving as a halogen atom source. The presence of
      two distinct environments for the chlorine atoms (Si-CCl2H and Si-Cl) and one
      type of bromine atom (Si-Br) was confirmed by Cl 2p, Br 3d, and C 1s X-ray
      photoelectron spectroscopy. The formation of reactive, halogen-terminated atop
      silicon sites was also verified by reaction with sodium azide or the Grignard
      reagent (CH3MgBr), to produce Si-N3 or Si-Me functionalities, respectively. Thus,
      reaction of a hydrogen-terminated silicon (111) surface with PhHgCCl2Br provides
      a facile route to multifunctional surfaces possessing both stable silicon-carbon
      and labile silicon-halogen sites, in a single pot synthesis. The reactive silicon
      halogen groups can be utilized for subsequent transformations and, potentially,
      the construction of more complex organic-silicon hybrid systems. 

PMID- 24328352
TI  - The importance of early identification and intervention for children with or at
      risk for autism spectrum disorders.
AB  - There has been a dramatic rise in the number of children being diagnosed with
      autism spectrum disorders (ASD), which has led to increased attention paid to
      assessment and intervention issues. This manuscript agrees with Camarata (2014)
      that the evidence base for early assessment and intervention should be expanded.
      However, it disagrees with Warren et al.'s (2011) assumption that there are not
      empirically validated early interventions. Reliable diagnosis has been documented
      during infancy and toddlerhood, and evidence suggests that the earlier the onset
      of intervention, the greater likelihood of an improved developmental trajectory.
      It is argued that early intervention is more cost and time efficient than a "wait
      and see" approach. With regard to published studies, the large amount of
      heterogeneity in the ASD population supports the use of rigorous single case
      experimental design research. It is an error to limit empirical evidence for
      treatments to only randomized clinical trials, which have the weakness of masking
      individual differences. Single case experimental designs examine the effects of
      intervention beyond typical maturation by allowing for clear estimations of
      developmental trajectories prior to the onset of intervention, followed by
      evaluation of the impact of the intervention. This commentary discusses the short
      and long-term benefits of early diagnosis and intervention.

PMID- 24328353
TI  - Peptide desorption kinetics from single molecule force spectroscopy studies.
AB  - We use a combined experimental/theoretical approach to determine the intrinsic
      monomeric desorption rate k0 of polytyrosine and polylysine homopeptides from
      flat surfaces. To this end, single polypeptide molecules are covalently attached
      to an AFM cantilever tip and desorbed from hydrophobic self-assembled monolayers
      in two complementary experimental protocols. In the constant-pulling-velocity
      protocol, the cantilever is moved at finite velocity away from the surface and
      the distance at which the constant plateau force regime ends and the polymer
      detaches is recorded. In the waiting-time protocol, the cantilever is held at a
      fixed distance above the surface and the time until the polymer detaches is
      recorded. The desorption plateau force is varied between 10 and 90 pN, by
      systematically changing the aqueous solvent quality via the addition of ethanol
      or salt. A simultaneous fit of the experimental data from both protocols with
      simple two-state kinetic polymer theory allows to unambiguously disentangle and
      determine the model parameters corresponding to polymer contour length L, Kuhn
      length a, adsorption free energy lambda, and intrinsic monomeric desorption rate
      k0. Crucial to our analysis is that a statistically significant number of single
      polymer desorption experiments are done with one and the same single polymer
      molecule for different solvent qualities. The surprisingly low value of about k0
      ~ 10(5) Hz points to significant cooperativity in the desorption process of
      single polymers. 

PMID- 24328354
TI  - Fully enclosed cylindrical single-electrode-based triboelectric nanogenerator.
AB  - We report a fully enclosed cylindrical single-electrode-based triboelectric
      nanogenerator (S-TENG) consisting of a perfluoroalkoxy (PFA) ball with surface
      etched nanowires, a floating latex balloon, and an Al electrode at the end of the
      balloon. The mechanism of the S-TENG includes two independent processes: contact
      induced electrification between the PFA ball and the balloon and electrostatic
      induction between the charged PFA ball and the Al electrode. The relationships
      between the electrical outputs and the sliding distance of the PFA ball were
      systematically investigated by combining experimental results with finite-element
      calculations. The S-TENG delivers an output voltage up to 236 V and a short
      circuit current of 4.8 MUA, which can be used as a direct power source for
      driving tens of green light-emitting diodes (LEDs). The S-TENG is a potential
      power source for gas-flow harvesters, air navigation, and environmental
      monitoring. 

PMID- 24328355
TI  - Mid-infrared spectrometer using opto-nanofluidic slot-waveguide for label-free on
      chip chemical sensing.
AB  - A mid-infrared (mid-IR) spectrometer for label-free on-chip chemical sensing was
      developed using an engineered nanofluidic channel consisting of a Si-liquid-Si
      slot-structure. Utilizing the large refractive index contrast (Deltan ~ 2)
      between the liquid core of the waveguide and the Si cladding, a broadband mid-IR
      lightwave can be efficiently guided and confined within a nanofluidic capillary
      (<=100 nm wide). The optical-field enhancement, together with the direct
      interaction between the probe light and the analyte, increased the sensitivity
      for chemical detection by 50 times when compared to evanescent-wave sensing. This
      spectrometer distinguished several common organic liquids (e.g., n-bromohexane,
      toluene, isopropanol) accurately and could determine the ratio of chemical
      species (e.g., acetonitrile and ethanol) at low concentration (<5 MUL/mL) in a
      mixture through spectral scanning over their characteristic absorption peaks in
      the mid-IR regime. The combination of CMOS-compatible planar mid-IR
      microphotonics, and a high-throughput nanofluidic sensor system, provides a
      unique platform for chemical detection. 

PMID- 24328356
TI  - DNA-triggered dye transfer on a quantum dot.
AB  - Nucleic acid-templated reactions are frequently explored tools in nucleic acid
      diagnosis. To enable a separation-free DNA detection, the reactive probe
      molecules require conjugation with reporter groups that provide measurable
      changes of an observable parameter upon reaction. A widely used, generic read-out
      method is based on fluorescence resonance energy transfer (FRET) between two
      appended dyes. Yet, spectral cross-talk usually limits the achievable
      enhancements of the FRET signal in DNA-directed chemistries. We describe a DNA
      triggered transfer reaction which provides for strong increases of a fluorescent
      signal caused by FRET. The method may involve DNA- and PNA-based probes and is
      based upon a proximity-triggered transfer reaction which leads to the covalent
      fixation of a fluorescence dye on the surface of a quantum dot (QD). The transfer
      reaction brings the dye closer to the QD than hybridization alone. The resulting
      FRET signal is a specific monitor of the reaction and allows efficient
      discrimination of single base mismatched templates. Of note, the 35-fold increase
      of the FRET signal is measured at 310 nm apparent Stokes shift and turnover in
      template provides a means for signal amplification. 

PMID- 24328357
TI  - Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated
      risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies.
AB  - AIMS: Statin treatment may impair glucose homeostasis and increase the risk of
      new-onset diabetes mellitus, although this may depend on the statin, dose and
      patient population. We evaluated the effects of pitavastatin 4 mg/day on glucose
      homeostasis in patients with metabolic syndrome in the CAPITAIN trial. Findings
      were validated in a subset of patients enrolled in PREVAIL-US. METHODS:
      Participants with a well defined metabolic syndrome phenotype were recruited to
      CAPITAIN to reduce the influence of confounding factors. Validation and
      comparison datasets were selected comprising phenotypically similar subsets of
      individuals enrolled in PREVAIL-US and treated with pitavastatin or pravastatin,
      respectively. Mean change from baseline in parameters of glucose homeostasis
      (fasting plasma glucose [FPG], glycated hemoglobin [HbA1c], insulin, quantitative
      insulin-sensitivity check index [QUICKI] and homeostasis model of assessment
      insulin resistance [HOMA-IR]) and plasma lipid profile were assessed at 6 months
      (CAPITAIN) and 3 months (PREVAIL-US) after initiating treatment. RESULTS: In
      CAPITAIN (n = 12), no significant differences from baseline in HbA1c, insulin,
      HOMA-IR and QUICKI were observed at day 180 in patients treated with
      pitavastatin. A small (4%) increase in FPG from baseline to day 180 (P < 0.05),
      was observed. In the validation dataset (n = 9), no significant differences from
      baseline in glycemic parameters were observed at day 84 (all comparisons P >
      0.05). Similar results were observed for pravastatin in the comparison dataset (n
      = 14). CONCLUSIONS: Other than a small change in FPG in the CAPITAIN study,
      neutral effects of pitavastatin on glucose homeostasis were observed in two
      cohorts of patients with metabolic syndrome, independent of its efficacy in
      reducing levels of atherogenic lipoproteins. The small number of patients and
      relatively short follow-up period represent limitations of the study.
      Nevertheless, these data suggest that statin-induced diabetogenesis may not
      represent a class effect.

PMID- 24328358
TI  - Solvation free energies of alanine peptides: the effect of flexibility.
AB  - The electrostatic (DeltaGel), van der Waals cavity-formation (DeltaGvdw), and
      total (DeltaG) solvation free energies for 10 alanine peptides ranging in length
      (n) from 1 to 10 monomers were calculated. The free energies were computed both
      with fixed, extended conformations of the peptides and again for some of the
      peptides without constraints. The solvation free energies, DeltaGel, and
      components DeltaGvdw, and DeltaG, were found to be linear in n, with the slopes
      of the best-fit lines being gammael, gammavdw, and gamma, respectively. Both
      gammael and gamma were negative for fixed and flexible peptides, and gammavdw was
      negative for fixed peptides. That gammavdw was negative was surprising, as
      experimental data on alkanes, theoretical models, and MD computations on small
      molecules and model systems generally suggest that gammavdw should be positive. A
      negative gammavdw seemingly contradicts the notion that DeltaGvdw drives the
      initial collapse of the protein when it folds by favoring conformations with
      small surface areas. When we computed DeltaGvdw for the flexible peptides,
      thereby allowing the peptides to assume natural ensembles of more compact
      conformations, gammavdw was positive. Because most proteins do not assume
      extended conformations, a DeltaGvdw that increases with increasing surface area
      may be typical for globular proteins. An alternative hypothesis is that the
      collapse is driven by intramolecular interactions. We find few intramolecular H
      bonds but show that the intramolecular van der Waals interaction energy is more
      favorable for the flexible than for the extended peptides, seemingly favoring
      this hypothesis. The large fluctuations in the vdw energy may make attributing
      the collapse of the peptide to this intramolecular energy difficult. 

PMID- 24328359
TI  - Resolving isotopic fine structure to detect and quantify natural abundance- and
      hydrogen/deuterium exchange-derived isotopomers.
AB  - Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) is used for analyzing
      protein dynamics, protein folding/unfolding, and molecular interactions. Until
      this study, HDX MS experiments employed mass spectral resolving powers that
      afforded only one peak per nominal mass in a given peptide's isotope
      distribution, and HDX MS data analysis methods were developed accordingly. A
      level of complexity that is inherent to HDX MS remained unaddressed, namely,
      various combinations of natural abundance heavy isotopes and exchanged deuterium
      shared the same nominal mass and overlapped at previous resolving powers. For
      example, an A + 2 peak is comprised of (among other isotopomers) a two-(2)H
      exchanged/zero-(13)C isotopomer, a one-(2)H-exchanged/one-(13)C isotopomer, and a
      zero-(2)H-exchanged/two-(13)C isotopomer. Notably, such isotopomers differ
      slightly in mass as a result of the ~3 mDa mass defect between (2)H and (13)C
      atoms. Previous HDX MS methods did not resolve these isotopomers, requiring a
      natural-abundance-only (before HDX or "time zero") spectrum and data processing
      to remove its contribution. It is demonstrated here that high-resolution mass
      spectrometry can be used to detect isotopic fine structure, such as in the A + 2
      profile example above, deconvolving the isotopomer species resulting from
      deuterium incorporation. Resolving isotopic fine structure during HDX MS
      therefore permits direct monitoring of HDX, which can be calculated as the sum of
      the fractional peak magnitudes of the deuterium-exchanged isotopomers. This
      obviates both the need for a time zero spectrum as well as data processing to
      account for natural abundance heavy isotopes, saving instrument and analysis
      time. 

PMID- 24328360
TI  - 'Getting to Know Me': the development and evaluation of a training programme for
      enhancing skills in the care of people with dementia in general hospital
      settings.
AB  - OBJECTIVE: The aims of the study were to report on the development and evaluation
      of a staff training intervention in dementia care designed for use in the general
      hospital setting: the 'Getting to Know Me' training programme. The study also
      aimed to undertake initial psychometric analysis on two new outcome scales
      designed to measure knowledge and confidence in dementia care. METHODS: The study
      comprised two phases. The first phase comprised the design of two questionnaires
      which are shared within this paper: Confidence in Dementia (CODE) Scale and
      Knowledge in Dementia (KIDE) Scale. In phase two, staff undertook the 'Getting to
      Know Me' training programme (n=71). The impact of the programme was evaluated
      using a pre-post design which explored: (1) changes in confidence in dementia;
      (2) changes in knowledge in dementia; and (3) changes in beliefs about
      challenging behaviour. RESULTS: The psychometric properties of the CODE and KIDE
      scales are reported. Statistically significant change was identified pre-post
      training on all outcome measures. Clinically meaningful change was demonstrated
      on the CODE scale. CONCLUSIONS: The 'Getting to Know Me' programme was well
      received and had a significant impact on staff knowledge and confidence. Our
      findings add to a growing evidence base which will be strengthened by further
      robust studies, the exploration of the impact of staff training on direct patient
      outcomes, and further identification of ways in which to transfer principles of
      care from specialist dementia environments into general hospital settings.

PMID- 24328361
TI  - Motility, viability, and calcium in the sperm cells.
AB  - Sperm cells are complicated in vitro models. Their viability is limited, and
      physiology is complex. The study of their properties is of great application in
      the animal production as viable and functional gametes are essential. It has been
      shown that the decrease of sperm cell viability parallels an increase of the
      reactive oxygen species (ROS). Reactive oxygen species is secondary to normal
      metabolic processes of the cell-like flagellar movement. There is evidence of
      strategies that reduce ROS levels by using exogenous or endogenous antioxidants
      with the intention that seminal plasma protects the sperm cells and increases
      viability. Perhaps viability can increase by reducing that flagellar movement
      which is regulated by calcium. The phenomenon has not been fully characterized,
      but it is established that in certain mammalian models, the entrance of calcium
      via specific channels such as CATsper or voltage-dependent channels, signals
      flagellar movement. Previous reports have indicated that a change in the
      concentration of calcium or if the temperature is altered, the function of mammal
      sperm cells is reduced or blocked and viability prolonged. Fish sperm can remain
      immobile for several weeks but when activated the number of mobile and viable
      sperm is reduced at a faster rate. However, if the cells are not mobilized the
      semen can be preserved for longer periods. As presented in this paper, this
      supports the notion that by modulating calcium channels to reduce motility the
      viability of these cells can increase.

PMID- 24328362
TI  - Adsorption of phenanthrene on multilayer graphene as affected by surfactant and
      exfoliation.
AB  - Surfactant mediated exfoliation of multilayer graphene and its effects on
      phenanthrene adsorption were investigated using a passive dosing technique. In
      the absence of surfactant (sodium cholate, NaC), multilayer graphene had higher
      adsorption capacity for phenanthrene than carbon nanotube and graphite due to the
      higher surface area and micropore volume. The observed desorption hysteresis is
      likely caused by the formation of closed interstitial spaces through folding and
      rearrangement of graphene sheets. In the presence of NaC (both 100 and 8000
      mg/L), phenanthrene adsorption on graphene was decreased due to the direct
      competition of NaC molecules on the graphene surface. With the aid of sonication,
      multilayer graphene sheets were exfoliated by NaC, leading to better dispersion.
      The degree of dispersion depended on the graphene-NaC ratio in aqueous solution
      rather than critical micelle concentration of NaC, and the good dispersion
      occurred after reaching adsorption saturation of NaC molecules on graphene
      sheets. In addition, exfoliation weakened the competition between phenanthrene
      and NaC and enhanced the adsorption capacity of graphene for phenanthrene due to
      exposed new sites. The findings on exfoliation of graphene sheets and related
      adsorption properties highlight not only the potential applications of multilayer
      graphene as efficient adsorbent but also its possible environmental risk. 

PMID- 24328363
TI  - Prediction of coating thickness in the convective assembly process.
AB  - Convective assembly is a coating method to fabricate thin films with ordered
      particle structures that can be used extensively for biochemical sensors, data
      storage devices, optical devices, and other applications. The fluid flow into or
      through the close-packed region causes the convective assembly, and it is
      important to understand the formation mechanism of the close-packed region. In
      this paper, the length of the close-packed region was predicted, and the
      dimensionless coating thickness as well as the dimensionless length of the close
      packed region was found to be the functions of only three dimensionless
      variables: two capillary numbers and the initial volume fraction. From the
      modeling results, coating process regime maps that predict the dimensionless
      coating thickness in terms of the dimensionless variables were created. In
      addition, the length of the close-packed region was measured under various
      coating conditions to validate the model prediction. The experiments firmly
      supported the model predictions. 

PMID- 24328364
TI  - Thermal stability of colloidal InP nanocrystals: small inorganic ligands boost
      high-temperature photoluminescence.
AB  - We examine the stability of excitons in quantum-confined InP nanocrystals as a
      function of temperature elevation up to 800 K. Through the use of static and time
      resolved spectroscopy, we find that small inorganic capping ligands substantially
      improve the temperature dependent photoluminescence quantum yield relative to
      native organic ligands and perform similarly to a wide band gap inorganic shell.
      For this composition, we identify the primary exciton loss mechanism as electron
      trapping through a combination of transient absorption and transient
      photoluminescence measurements. Density functional theory indicates little impact
      of studied inorganic ligands on InP core states, suggesting that reduced thermal
      degradation relative to organic ligands yields improved stability; this is
      further supported by a lack of size dependence in photoluminescence quenching,
      pointing to the dominance of surface processes, and by relative thermal
      stabilities of the surface passivating media. Thus, small inorganic ligands,
      which benefit device applications due to improved carrier access, also improve
      the electronic integrity of the material during elevated temperature operation
      and subsequent to high temperature material processing. 

PMID- 24328365
TI  - Comparative study on the use of docking and Bayesian categorization to predict
      ligand binding to nicotinic acetylcholine receptors (nAChRs) subtypes.
AB  - We have carried out a comparative study between docking into homology models and
      Bayesian categorization, as applied to virtual screening of nicotinic ligands for
      binding at various nAChRs subtypes (human and rat alpha4beta2, alpha7,
      alpha3beta4, and alpha6beta2beta3). We found that although results vary with
      receptor subtype, Bayesian categorization exhibits higher accuracy and enrichment
      than unconstrained docking into homology models. However, docking accuracy is
      improved when one sets up a hydrogen-bond (HB) constraint between the cationic
      center of the ligand and the main-chain carbonyl group of the conserved Trp-149
      or its homologue (a residue involved in cation-pi interactions with the ligand
      basic nitrogen atom). This finding suggests that this HB is a hallmark of
      nicotinic ligands binding to nAChRs. Best predictions using either docking or
      Bayesian were obtained with the human alpha7 nAChR, when 100 nM was used as
      cutoff for biological activity. We also found that ligand-based Bayesian-derived
      enrichment factors and structure-based docking-derived enrichment factors highly
      correlate to each other. Moreover, they correlate with the mean molecular
      fractional polar surface area of actives ligands and the fractional
      hydrophobic/hydrophilic surface area of the binding site, respectively. This
      result is in agreement with the fact that hydrophobicity strongly contributes in
      promoting nicotinic ligands binding to their cognate nAChRs. 

PMID- 24328367
TI  - Challenges and opportunities in early identification and intervention for
      children at-risk for autism spectrum disorders.
AB  - This response to Camarata (2014) both agrees and disagrees with a number of
      points relative to early identification and intervention for children with autism
      spectrum disorders (ASD). The authors, too, recognize the difficulties of
      identifying toddlers with ASD and the complexities of intervening with these
      children. It is, however, suggested that there are alternatives to choosing to
      wait until diagnoses for at-risk children are stable and it is believed that
      there are many potential benefits from intervening, even when stable diagnoses
      cannot be made at the time, but risk markers are present. Specifically, it is
      suggested that it is not necessary to differentially diagnose children in efforts
      to evaluate treatment effects and suggestions are provided for alternative
      methods. This commentary also acknowledges the importance of effective ASD
      screening tools, along with expert clinical opinion, to help identify these
      toddlers with and at-risk for ASD. Both the available literature from other
      researchers as well as the authors' own work in these areas are used to make
      these arguments.

PMID- 24328366
TI  - Redox-neutral alpha-arylation of amines.
AB  - The direct alpha-arylation/N-alkylation of cyclic amines was achieved in a redox
      neutral fashion under mild conditions. Transformations occur in the absence of
      any additives or are promoted by simple carboxylic acids. 

PMID- 24328368
TI  - Thermosensitive hydrogel from oligopeptide-containing amphiphilic block
      copolymer: effect of peptide functional group on self-assembly and gelation
      behavior.
AB  - We reveal that a slight change in the functional group of the oligopeptide block
      incorporated into the poloxamer led to drastically different hierarchical
      assembly behavior and rheological properties in aqueous media. An oligo(L-Ala-co
      L-Phe-co-beta-benzyl L-Asp)-poloxamer-oligo(beta-benzyl-L-Asp-co-L-Phe-co-L-Ala)
      block copolymer (OAF-(OAsp(Bzyl))-PLX-(OAsp(Bzyl))-OAF, denoted as polymer 1),
      which possessed benzyl group on the aspartate moiety of the peptide block, was
      synthesized through ring-opening polymerization. The benzyl group on aspartate
      was then converted to carboxylic acid to yield oligo(L-Ala-co-L-Phe-co-L-Asp)
      poloxamer-oligo(L-Asp-co-L-Phe-co-L-Ala) (OAF-(OAsp)-PLX-(OAsp)-OAF, denoted as
      polymer 2). Characterization of the peptide secondary structure in aqueous media
      by circular dichroism revealed that the oligopeptide block in polymer 1 exhibited
      mainly an alpha-helix conformation, whereas that in polymer 2 adopted
      predominantly a beta-sheet conformation at room temperature. The segmental
      dynamics of the PEG in polymer 1 remained essentially unperturbed upon heating
      from 10 to 50  degrees C; by contrast, the PEG segmental motion in polymer 2
      became more constrained above ca. 35  degrees C, indicating an obvious change in
      the chemical environment of the block chains. Meanwhile, the storage modulus of
      the polymer 2 solution underwent an abrupt increase across this temperature, and
      the solution turned into a gel. Wet-cell TEM observation revealed that polymer 1
      self-organized to form microgel particles of several hundred nanometers in size.
      The microgel particle was retained as the characteristic morphological entity
      such that the PEG chains did not experience a significant change of their
      chemical environment upon heating. The hydrogel formed by polymer 2 was found to
      contain networks of nanofibrils, suggesting that the hydrogen bonding between the
      carboxylic acid groups led to an extensive stacking of the beta sheets along the
      fibril axis at elevated temperature. The in vitro cytotoxicity of the polymer 2
      aqueous solution was found to be low in human retinal pigment epithelial cells.
      The low cytotoxicity coupled with the sol-gel transition makes the corresponding
      hydrogel a good candidate for biomedical applications.

PMID- 24328369
TI  - Statistical pull off of nanoparticles adhering to compliant substrates.
AB  - It is widely known in adhesive contact mechanics that a spherical particle will
      not detach from an elastic half-space unless a critical level of pulling force is
      reached, as already revealed by JKR- or DMT-type deterministic models. This
      article focuses on the scenario of particle-substrate adhesion where the size of
      particles is down to the nanometer scale. A consequence of particle size
      reduction to this range is that the energy scale confining the state of system
      equilibrium becomes comparable to the unit of thermal energy, leading to
      statistical particle detachment even below the critical pull-off force. We
      describe the process by Kramers' theory as a thermally activated escape from an
      energy well and develop a Smoluchowski partial differential equation that governs
      the spatial-temporal evolution of the adhesion state in probabilistic terms.
      These results show that the forced or spontaneous separation of nanometer-sized
      particles from compliant substrates occurs diffusively and statistically rather
      than ballistically and deterministically as assumed in existing models. 

PMID- 24328370
TI  - NIR J-aggregates of hydroazaheptacene tetraimides.
AB  - Hydroazaacene dicarboximide derivatives with red to NIR absorptions are designed
      and synthesized, which exhibit well-defined J-aggregation behaviors in both
      solution and thin films. The absorption and emission of an aggregate extend well
      into the NIR regime (lambda(max) = 902 nm), manifesting particularly narrow
      bandwidth (fwhm = 152 cm(-1)) and is nearly transparent in the visible region.

PMID- 24328371
TI  - Dual labeling of lipopolysaccharides for SPECT-CT imaging and fluorescence
      microscopy.
AB  - Lipopolysaccharides (LPS) or endotoxins are amphipathic, pro-inflammatory
      components of the outer membrane of Gram-negative bacteria. In the host, LPS can
      trigger a systemic inflammatory response syndrome. To bring insight into in vivo
      tissue distribution and cellular uptake of LPS, dual labeling was performed with
      a bimodal molecular probe designed for fluorescence and nuclear imaging. LPS were
      labeled with DOTA-Bodipy-NCS, and pro-inflammatory properties were controlled
      after each labeling step. LPS were then radiolabeled with (111)In and
      subsequently injected intravenously into wild-type, C57B16 mice, and their in
      vivo behavior was followed by single photon emission computed tomography coupled
      with X-ray computed tomography (SPECT-CT) and fluorescence microscopy. Time
      course of liver uptake of radiolabeled LPS ((111)In-DOTA-Bodipy-LPS) was
      visualized over a 24-h period in the whole animal by SPECT-CT. In complementary
      histological analyses with fluorescent microscopy, the bulk of injected (111)In
      DOTA-Bodipy-LPS was found to localize early within the liver. Serum kinetics of
      unlabeled and DOTA-Bodipy-labeled LPS in mouse plasma were similar as ascertained
      by direct quantitation of beta-hydroxymyristate, and DOTA-Bodipy-LPS was found to
      retain the potent, pro-inflammatory property of the unlabeled molecule as
      assessed by serum cytokine assays. It is concluded that the dual labeling
      process, involving the formation of covalent bonds between a DOTA-Bodipy-NCS
      probe and LPS molecules is relevant for imaging and kinetic analysis of LPS
      biodistribution, both in vivo and ex vivo. Data of the present study come in
      direct and visual support of a lipopolysaccharide transport through which pro
      inflammatory LPS can be transported from the periphery to the liver for
      detoxification. The (111)In-DOTA-Bodipy-LPS probe arises here as a relevant tool
      to identify key components of LPS detoxification in vivo. 

PMID- 24328373
TI  - Could fecal microbiota transplantation cure all Clostridium difficile infections?

PMID- 24328374
TI  - Integrons: epidemiological molecular markers for identifying and surveying
      metallo-beta-lactamase genes in Gram-negative bacilli.

PMID- 24328372
TI  - Invasive and non-invasive techniques for detecting portal hypertension and
      predicting variceal bleeding in cirrhosis: a review.
AB  - Portal hypertension is a severe syndrome that may derive from pre-sinusoidal,
      sinusoidal, and post-sinusoidal causes. As a consequence, several complications
      (i.e. ascites, oesophageal varices) may develop. In sinusoidal portal
      hypertension, hepatic venous pressure gradient (HVPG) is a reliable method for
      defining the grade of portal pressure, establishing the effectiveness of the
      treatment, and predicting the occurrence of complications; however, some
      questions exist regarding its ability to discriminate bleeding from non-bleeding
      varices in cirrhotic patients. Other imaging techniques (transient elastography,
      endoscopy, endosonography, and duplex Doppler sonography) for assessing causes
      and complications of portal hypertensive syndrome are available and may be
      valuable for the management of these patients. In this review, we evaluate
      invasive and non-invasive techniques currently employed to obtain a clinical
      prediction of deadly complications, such as variceal bleeding in patients
      affected by sinusoidal portal hypertension, in order to create a diagnostic
      algorithm to manage them. Again, HVPG appears to be the reference standard to
      evaluate portal hypertension and monitor the response to treatment, but its
      ability to predict several complications and support management decisions might
      be further improved through the diagnostic combination with other imaging
      techniques.

PMID- 24328376
TI  - How enteric pathogens know they hit the sweet spot.
AB  - EVALUATION OF: Ng KM, Ferreyra JA, Higginbottom SK et al. Microbiota-liberated
      host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature
      502(7469), 96-99 (2013). The human gut microbiota is a complex system of
      commensal microorganisms required for normal host physiology. Disruption of this
      protective barrier by antibiotics creates opportunities for enteric pathogens to
      establish infections. Although the correlation between the use of antibiotics and
      enteric infections have been known for some time, the specific signals that allow
      enteric pathogens to recognize a susceptible host have not been determined. In a
      recent article, Ng et al. demonstrated that the expansion of both Salmonella
      typhimurium and Clostridium difficile infections is enhanced by the availability
      of host-specific sugars liberated from the intestinal mucus by commensal
      bacteria. These results show how antibiotic removal of specific species from the
      gut microbiome allows symbiotic functions to be hijacked by pathogenic species.

PMID- 24328377
TI  - The clinical and public health challenge of Gram-negative resistance in
      Australasia.
AB  - The Gram-Negative 'Superbugs' Conference of the Australasian Society for
      Infectious Diseases, Gold Coast, Queensland, Australia, 2-3 August 2013 The
      Australian Society for Infectious Diseases hosted a national conference focused
      specifically on raising awareness of and contemplating solutions to the rise in
      antimicrobial resistance, especially in Gram-negative bacteria. Presentations
      were primarily informative, although some lively interactive sessions were held,
      particularly to debate contentious areas and to discuss options for policy makers
      and practitioners in infection control and antimicrobial stewardship. The
      conference brought together a diversity of backgrounds and interests, and was the
      first national meeting focused on this area. 

PMID- 24328378
TI  - A novel PCR-based genotyping scheme for clinical Klebsiella pneumoniae.
AB  - AIM: To establish a PCR-based genotyping method for clinical Klebsiella
      pneumoniae. MATERIALS & METHODS: The prevalence of six serotype markers, 41 large
      variably presented gene clusters, and seven additional virulence markers were
      screened by PCR in 327 clinical K. pneumoniae strains from China. RESULTS:
      Detection of serotype markers enabled the identification of capsular serotypes
      K1, K2, K5, K20, K54 and K57. K. pneumoniae isolates of different origins gave
      distinct profiles of virulence loci, allowing us to gain a full overview of
      virulence gene distribution of the strains tested. A novel genotyping scheme was
      established to group clinical K. pneumoniae strains into distinct complexes based
      on the profiles of large variably presented gene clusters and virulence markers.
      CONCLUSION: This PCR-based genotyping method would be useful to not only
      characterize genetic diversity and virulence gene distribution, but also for
      genotyping, origin tracing and risk estimation of K. pneumoniae.

PMID- 24328379
TI  - New Delhi metallo-beta-lactamase-producing Acinetobacter baumannii: a novel
      paradigm for spreading antibiotic resistance genes.
AB  - The impact of carbapenemase production among clinically significant Gram-negative
      rods is becoming a major medical issue. To date, Acinetobacter baumannii has been
      considered as a final recipient of carbapenemase genes (imipenemase, Verona
      metallo-beta-lactamase, Guiana extended-spectrum beta-lactamase and Klebsiella
      pneumonia carbapenemase types) from Enterobacteriaceae and Pseudomonas
      aeruginosa. However, recent findings regarding the spread of the blaNDM
      carbapenemase genes revealed that A. baumannii likely acts as a source of
      emerging antibiotic resistance genes. The analysis of genetic structure
      surrounding the blaNDM-1 gene revealed that the genetic structure (Tn125)
      responsible for its dissemination most probably originates from Acinetobacter.
      Moreover, analysis of the blaNDM-1 gene itself demonstrated that it might be
      constructed in Acinetobacter through a recombination event with another
      resistance gene found in A. baumannii (aphA6). This novel paradigm highlights a
      novel and unexpected role played by A. baumannii. 

PMID- 24328380
TI  - Leprosy as a model of immunity.
AB  - Leprosy displays a spectrum of clinical manifestations, such as lepromatous and
      tuberculoid leprosy, and type I and II lepra reactions, which are thought to be a
      reflection of the host's immunological response against Mycobacterium leprae.
      Therefore, differential recognition of M. leprae, as well as its degraded
      components, and subsequent activation of cellular immunity will be an important
      factor for the clinical manifestation of leprosy. Although M. leprae mainly
      parasitizes tissue macrophages in the dermis and the Schwann cells of peripheral
      nerves, the presence of M. leprae in other organs, such as the liver, may also
      play important roles in the further modification of seesaw-like bipolar
      phenotypes of leprosy. Thus, leprosy is an exciting model for investigating the
      role of the human immune system in host defense and susceptibility to infection. 

PMID- 24328381
TI  - Antiviral potential of cathelicidins.
AB  - The global burden of morbidity and mortality arising from viral infections is
      high; however, the development of effective therapeutics has been slow. As our
      understanding of innate immunity has expanded over recent years, knowledge of
      natural host defenses against viral infections has started to offer potential for
      novel therapeutic strategies. An area of current research interest is in
      understanding the roles played by naturally occurring cationic host defense
      peptides, such as the cathelicidins, in these innate antiviral host defenses
      across different species. This research also has the potential to inform the
      design of novel synthetic antiviral peptide analogs and/or provide rationale for
      therapies aimed at boosting the natural production of these peptides. In this
      review, we will discuss our knowledge of the antiviral activities of
      cathelicidins, an important family of cationic host defense peptides, and
      consider the implications for novel antiviral therapeutic approaches. 

PMID- 24328382
TI  - Staphylococci: colonizers and pathogens of human skin.
AB  - Staphylococci are abundant bacteria of the human skin microbiome. Several
      species, particularly Staphylococcus aureus and Staphylococcus epidermidis, are
      opportunistic pathogens and cause significant disease. The human skin serves many
      functions and here we review its role as an antimicrobial barrier and the
      staphylococcal mechanisms to colonize and counteract the various stresses present
      in this niche. Successful colonization is achieved using a diversity of adhesins,
      surface proteins and secreted enzymes to counteract the antimicrobial peptides,
      enzymes and lipid matrix components present in the acid mantle. Further
      mechanisms enable these bacteria to overcome osmotic and acid stresses and
      desiccation in order to survive the exacting demands of an ever-changing
      landscape. 

PMID- 24328383
TI  - Diseases caused by nontuberculous mycobacteria in Asia.
AB  - The isolation rate of nontuberculous mycobacteria (NTM) species and the
      prevalence of NTM-associated diseases are on the rise in Asian, as well as in
      Western countries; however, the species distribution of NTM isolates and the
      types of diseases caused by NTM species vary from region to region. In this
      review, we present an update on the epidemiology of NTM in Asia. We demonstrate
      that the distribution of NTM species varies within Asia and differs from that in
      North America and Europe. In addition, the clinical manifestations of NTM
      diseases include respiratory tract infections, disseminated infections, skin and
      soft tissue infections, lymphadenitis, empyema, ocular infections, CNS infections
      and genitourinary infections. Finally, the rate of adaptive resistance of anti
      NTM antimicrobial agents remains high and may be associated with a poor outcome
      for patients with NTM diseases. 

PMID- 24328384
TI  - Programmed cell death in Legionella infection.
AB  - The causative agent of Legionnaires' disease, Legionella pneumophila, resides
      within alveolar macrophages by exporting 295 bacterial virulence proteins
      (effectors) to modulate host cell processes. This leads to the formation of a
      unique vacuolar niche and the suppression of macrophage cell death pathways,
      which, in turn, promote bacterial survival and allow sufficient time for
      replication. However, once nutrients within the vacuole are depleted, Legionella
      must act to induce host cell death in order to facilitate bacterial egress and
      reinfect new cells. Intracellular Legionella also evade detection by the host
      cell's innate immune system, which seeks to destroy invading pathogens by
      activating inflammasome complexes, thereby promoting proinflammatory cytokine
      activation and pyroptotic cell death. Understanding how different forms of
      programmed cell death contribute to Legionella infectivity and are manipulated by
      Legionella effector proteins will be important for identifying novel
      antibacterial therapeutic targets. 

PMID- 24328385
TI  - Size dependence of negative trion Auger recombination in photodoped CdSe
      nanocrystals.
AB  - We report a systematic investigation of the size dependence of negative trion (T(
      )) Auger recombination rates in free-standing colloidal CdSe nanocrystals.
      Colloidal n-type CdSe nanocrystals of various radii have been prepared
      photochemically, and their trion decay dynamics have been measured using time
      resolved photoluminescence spectroscopy. Trion Auger time constants spanning 3
      orders of magnitude are observed, ranging from 57 ps (radius R = 1.4 nm) to 2.2
      ns (R = 3.2 nm). The data reveal a substantially stronger size dependence than
      found for bi- or multiexciton Auger recombination in CdSe or other semiconductor
      nanocrystals, scaling in proportion to R(4.3).

PMID- 24328387
TI  - Weight loss through adjustable gastric banding and improvement in daytime
      sleepiness: 2 year interim results of APEX study.
AB  - OBJECTIVE: Obesity is one factor associated with an increased risk of obstructive
      sleep apnea (OSA). This study reports the investigator-reported resolution or
      improvement of OSA and improvements in sleep-related quality of life (QOL) 2
      years after surgical placement of the LAP-BAND AP * (LBAP) system. RESEARCH
      DESIGN AND METHODS: The LBAP Experience (APEX) study is an ongoing 5 year,
      prospective, observational study assessing change in weight, comorbidities, and
      QOL after LBAP implantation. This is an interim analysis of patients with
      evaluable data at 24 months who had OSA at baseline. CLINICAL TRIAL REGISTRATION:
      NCT00501085. RESULTS: At baseline, 117 of 395 patients (29.6%; mean body mass
      index [BMI], 45.0 kg/m2) reported OSA; of these, 57 had evaluable patient
      reported outcome data at 2 years. Investigator-reported resolution or improvement
      of OSA was 69% and 86% at post-operative years 1 and 2, respectively. Patients
      reporting resolution, improvement, or no change in OSA experienced mean changes
      in BMI and percentage of weight loss of -9.7 kg/m(2)/-21.7%, -8.3 kg/m(2)/-18.7%,
      and -5.7 kg/m(2)/-13.2%, respectively (n = 54). Mean 2 year BMI was not
      statistically different between the groups (p = not significant). Mean scores for
      all Epworth Sleepiness Scale responses for the OSA population improved by -0.43
      from baseline (p < 0.0001; n = 78) compared with -0.29 for patients without OSA
      at baseline (n = 177; p = 0.037 between groups). In addition, the overall study
      population experienced resolution and/or improvement in other obesity-related
      comorbidities, such as type 2 diabetes (96%) and hypertension (91%). CONCLUSIONS:
      These data support that surgically facilitated weight loss can improve sleep
      related QOL and may result in resolution or improvement of OSA; the degree of
      weight loss may be related to these changes.

PMID- 24328389
TI  - Factors that influence suicidal ideation among elderly Korean immigrants: focus
      on diatheses and stressors.
AB  - OBJECTIVES: The study examined major diatheses and stressors directly related to
      suicidal ideation among elderly Korean immigrants. The study also explored the
      significant interactions among these factors. METHOD: Data were collected from a
      cross-sectional survey of 220 elderly Korean immigrants (age >= 65) in Los
      Angeles County. RESULTS: Using a robust hierarchical regression, the study found
      that neuroticism and hopelessness were significantly associated with suicidal
      ideation. In addition, two interaction terms - neuroticism by hopelessness and
      neuroticism by acculturation - were both significant predictor variables with
      strong explanatory power. CONCLUSION: The theoretical implications as well as the
      practical implications for developing and implementing late-life suicide
      prevention strategies are discussed.

PMID- 24328388
TI  - Resonance Raman spectroscopy reveals that substrate structure selectively impacts
      the heme-bound diatomic ligands of CYP17.
AB  - An important function of steroidogenic cytochromes P450 is the transformation of
      cholesterol to produce androgens, estrogens, and the corticosteroids. The
      activities of cytochrome P450c17 (CYP17) are essential in sex hormone
      biosynthesis, with severe developmental defects being a consequence of deficiency
      or mutations. The first reaction catalyzed by this multifunctional P450 is the
      17alpha-hydroxylation of pregnenolone (PREG) to 17alpha-hydroxypregnenolone (17
      OH PREG) and progesterone (PROG) to 17alpha-hydroxyprogesterone (17-OH PROG). The
      hydroxylated products then either are used for production of corticoids or
      undergo a second CYP17 catalyzed transformation, representing the first committed
      step of androgen formation. While the hydroxylation reactions are catalyzed by
      the well-known Compound I intermediate, the lyase reaction is believed to involve
      nucleophilic attack of the earlier peroxo- intermediate on the C20-carbonyl.
      Herein, resonance Raman (rR) spectroscopy reveals that substrate structure does
      not impact heme structure for this set of physiologically important substrates.
      On the other hand, rR spectra obtained here for the ferrous CO adducts with these
      four substrates show that substrates do interact differently with the Fe-C-O
      fragment, with large differences between the spectra obtained for the samples
      containing 17-OH PROG and 17-OH PREG, the latter providing evidence for the
      presence of two Fe-C-O conformers. Collectively, these results demonstrate that
      individual substrates can differentially impact the disposition of a heme-bound
      ligand, including dioxygen, altering the reactivity patterns in such a way as to
      promote preferred chemical conversions, thereby avoiding the profound functional
      consequences of unwanted side reactions. 

PMID- 24328390
TI  - Probing the location of hot spots by surface-enhanced Raman spectroscopy: toward
      uniform substrates.
AB  - Wide applications of surface plasmon resonance rely on the in-depth understanding
      of the near-field distribution over a metallic nanostructure. However, precisely
      locating the strongest electric field in a metallic nanostructure still remains a
      great challenge in experiments because the field strength decays exponentially
      from the surface. Here, we demonstrate that the hot spot position for gold
      nanoparticles over a metal film can be precisely located using surface-enhanced
      Raman spectroscopy (SERS) by rationally choosing the probe molecules and
      excitation wavelengths. The finite difference time domain simulation verifies the
      experimental results and further reveals that the enhancement for the above
      system is sensitive to the distance between nanoparticles and the metal film but
      insensitive to the distance of nanoparticles. On the basis of this finding, we
      propose and demonstrate an approach of using a nanoparticles-on-metal film
      substrate as a uniform SERS substrate. This work provides a convenient way to
      probe the location of strong near-field enhancement with SERS and will have
      important implications in both surface analysis and surface plasmonics. 

PMID- 24328391
TI  - Peak distortion effects in analytical ion chromatography.
AB  - The elution profile of chromatographic peaks provides fundamental understanding
      of the processes that occur in the mobile phase and the stationary phase. Major
      advances have been made in the column chemistry and suppressor technology in ion
      chromatography (IC) to handle a variety of sample matrices and ions. However, if
      the samples contain high concentrations of matrix ions, the overloaded peak
      elution profile is distorted. Consequently, the trace peaks shift their positions
      in the chromatogram in a manner that depends on the peak shape of the overloading
      analyte. In this work, the peak shapes in IC are examined from a fundamental
      perspective. Three commercial IC columns AS16, AS18, and AS23 were studied with
      borate, hydroxide and carbonate as suppressible eluents. Monovalent ions
      (chloride, bromide, and nitrate) are used as model analytes under analytical (0.1
      mM) to overload conditions (10-500 mM). Both peak fronting and tailing are
      observed. On the basis of competitive Langmuir isotherms, if the eluent anion is
      more strongly retained than the analyte ion on an ion exchanger, the analyte peak
      is fronting. If the eluent is more weakly retained on the stationary phase, the
      analyte peak always tails under overload conditions regardless of the stationary
      phase capacity. If the charge of the analyte and eluent anions are different
      (e.g., Br(-) vs CO3(2-)), the analyte peak shapes depend on the eluent
      concentration in a more complex pattern. It was shown that there are interesting
      similarities with peak distortions due to strongly retained mobile phase
      components in other modes of liquid chromatography. 

PMID- 24328392
TI  - Evaluating the environmental impacts of a nano-enhanced field emission display
      using life cycle assessment: a screening-level study.
AB  - Carbon nanotube (CNT) field emission displays (FEDs) are currently in the product
      development stage and are expected to be commercialized in the near future
      because they offer image quality and viewing angles comparable to a cathode ray
      tube (CRT) while using a thinner structure, similar to a liquid crystal display
      (LCD), and enable more efficient power consumption during use. To address
      concerns regarding the environmental performance of CNT-FEDs, a screening-level,
      cradle-to-grave life cycle assessment (LCA) was conducted based on a functional
      unit of 10,000 viewing hours, the viewing lifespan of a CNT-FED. Contribution
      analysis suggests the impacts for material acquisition and manufacturing are
      greater than the combined impacts for use and end-of-life. A scenario analysis of
      the CNT paste composition identifies the metal components used in the paste are
      key contributors to the impacts of the upstream stages due to the impacts
      associated with metal preparation. Further improvement of the manufacturing
      impacts is possible by considering the use of plant-based oils, such as rapeseed
      oil, as alternatives to organic solvents for dispersion of CNTs. Given the
      differences in viewing lifespan, the impacts of the CNT-FED were compared with a
      LCD and a CRT display to provide more insight on how to improve the CNT-FED to
      make it a viable product alternative. When compared with CRT technology, CNT-FEDs
      show better environmental performance, whereas a comparison with LCD technology
      indicates the environmental impacts are roughly the same. Based on the results,
      the enhanced viewing capabilities of CNT-FEDs will be a more viable display
      option if manufacturers can increase the product's expected viewing lifespan.

PMID- 24328394
TI  - The deeper significance of integrative medicine.

PMID- 24328393
TI  - Meditation training for people with amyotrophic lateral sclerosis and their
      caregivers.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal
      neurodegenerative disease that is clinically characterized by progressive
      weakness leading to death by respiratory insufficiency, usually within three
      years. Although the patient's intellect and personality usually remain
      unimpaired, as the disease progresses, the patient becomes immobile, develops
      wasting, and speech becomes impaired, often resulting in social isolation and a
      high degree of psychological suffering. Mindfulness meditation has proven to be
      effective technique for reducing distress in many chronic diseases. However, to
      date, no study has investigated the effect of mindfulness meditation on patients
      with ALS. DESIGN: A mindfulness meditation training program for ALS patients
      needs to consider the particularities of ALS symptoms, including the loss of
      muscular functions and difficulties in respiration, together with the subsequent
      emotional impairments. With these caveats in mind, a modified protocol, based on
      original mindfulness meditation interventions, has been created specifically for
      the ALS population. This article describes the protocol and preliminary results.

PMID- 24328395
TI  - Conventional and complex modal analyses of a finite element model of human head
      and neck.
AB  - This study employs both the traditional and the complex modal analyses of a
      detailed finite element model of human head-neck system to determine modal
      responses in terms of resonant frequencies and mode shapes. It compares both
      modal responses without ignoring mode shapes, and these results are reasonably in
      agreement with the literature. Increasing displacement contour loops within the
      brain in higher frequency modes probably exhibits the shearing and twisting modes
      of the brain. Additional and rarely reported modal responses such as
      'mastication' mode of the mandible and flipping mode of nasal lateral cartilages
      are identified. This suggests a need for detailed modelling to identify all the
      additional frequencies of each individual part. Moreover, it is found that a
      damping factor of above 0.2 has amplifying effect in reducing higher frequency
      modes, while a diminishing effect in lowering peak biomechanical responses,
      indicating the importance of identifying the appropriate optimised damping
      factor.

PMID- 24328396
TI  - Copper-catalyzed intermolecular cyanotrifluoromethylation of alkenes.
AB  - A novel and highly practical reaction for the copper-catalyzed intermolecular
      cyanotrifluoromethylation of alkenes is presented here. This methodology provides
      a general and straightforward way to synthesize a variety of useful CF3
      containing nitriles, which can be used for further preparation of
      pharmaceutically and agrochemically important compounds in synthetic organic
      chemistry. 

PMID- 24328397
TI  - Persistence of extracellular DNA in river sediment facilitates antibiotic
      resistance gene propagation.
AB  - The propagation of antibiotic resistance genes (ARGs) represents a global threat
      to both human health and food security. Assessment of ARG reservoirs and
      persistence is therefore critical for devising and evaluating strategies to
      mitigate ARG propagation. This study developed a novel, internal standard method
      to extract extracellular DNA (eDNA) and intracellular DNA (iDNA) from water and
      sediments, and applied it to determine the partitioning of ARGs in the Haihe
      River basin in China, which drains an area of intensive antibiotic use. The
      concentration of eDNA was higher than iDNA in sediment samples, likely due to the
      enhanced persistence of eDNA when associated with clay particles and organic
      matter. Concentrations of sul1, sul2, tetW, and tetT antibiotic resistance genes
      were significantly higher in sediment than in water, and were present at higher
      concentrations as eDNA than as iDNA in sediment. Whereas ARGs (frequently located
      on plasmid DNA) were detected for over 20 weeks, chromosomally encoded 16S rRNA
      genes were undetectable after 8 weeks, suggesting higher persistence of plasmid
      borne ARGs in river sediment. Transformation of indigenous bacteria with added
      extracellular ARG (i.e., kanamycin resistance genes) was also observed.
      Therefore, this study shows that extracellular DNA in sediment is a major ARG
      reservoir that could facilitate antibiotic resistance propagation. 

PMID- 24328398
TI  - Slow and fast dietary proteins differentially modulate postprandial metabolism.
AB  - The quality of dietary proteins is influenced by their content and composition of
      amino acids and bioavailability. Recent data suggest that the digestion and
      absorption kinetics of proteins influences the effects of protein ingestion on
      the metabolic processes. Slowly and fast-digested dietary proteins differentially
      modulate postprandial protein and glucose metabolism. This is an important factor
      for defining the physiological outcome and application for nutritional purposes
      of different dietary protein sources.

PMID- 24328399
TI  - Characterization and the effect of maturity at harvest on the phenolic and
      carotenoid content of Northeast USA Apricot (Prunus armeniaca) varieties.
AB  - The phenolic and carotenoid content and quality indices of five Northeast apricot
      varieties were assessed over two years and the impact of maturity at harvest was
      evaluated. Four varieties were analyzed at commercial and tree ripe stages and
      one variety after storage for 4 weeks (0-1  degrees C, 90-95% relative humidity).
      Total phenolic content ranged from 44.0 to 345.1 mg/100 g, total antioxidant
      capacity (oxygen radical absorbance capacity assay) from 2096.9 to 7165.1
      MUmol/100 g, and total carotenoid content from 1312.1 to 7371.1 MUg/100, fresh
      weight. 'Hargrand' apricot had the highest phenolic and carotenoid content.
      Catechin, chlorogenic acid, and neochlorogenic acid were the predominant phenolic
      compounds and beta-carotene was the predominant carotenoid compound. Carotenoid
      content increased with ripening and postharvest storage while changes in phenolic
      content and antioxidant capacity were variety-dependent. Results show the apricot
      varieties studied to be good or excellent sources of vitamin A despite moderate
      carotenoid content attributed to cultivation in a colder climate. 

PMID- 24328400
TI  - Auranofin is an apoptosis-simulating agent with in vitro and in vivo anti
      leishmanial activity.
AB  - Cutaneous leishmaniasis remains ignored in therapeutic drug discovery programs
      worldwide. This is mainly because cutaneous leishmaniasis is frequently a disease
      of impoverished populations in countries where funds are limited for research and
      patient care. However, the health burden of individuals in endemic areas mandates
      readily available, effective, and safe treatments. Of the existing cutaneous
      leishmaniasis therapeutics, many are growth inhibitory to Leishmania parasites,
      potentially creating dormant parasite reservoirs that can be activated when host
      immunity is compromised, enabling the reemergence of cutaneous leishmaniasis
      lesions or worse spread of Leishmania parasites to other body sites. To
      accelerate the identification and development of novel cutaneous leishmaniasis
      therapeutics, we designed an integrated in vitro and in vivo screening platform
      that incorporated multiple Leishmania life cycles and species and probed a
      focused library of pharmaceutically active compounds. The objective of this
      phenotypic drug discovery platform was the identification and prioritization of
      bona fide cytotoxic chemotypes toward Leishmania parasites. We identified the
      Food and Drug Administration-approved drug auranofin, a known inhibitor of
      Leishmania promastigote growth, as a potent cytotoxic anti-leishmanial agent and
      inducer of apoptotic-like death in promastigotes. Significantly, the anti
      leishmanial activity of auranofin transferred to cell-based amastigote assays as
      well as in vivo murine models. With appropriate future investigation, these data
      may provide the foundation for potential exploitation of gold(I)-based complexes
      as chemical tools or the basis of therapeutics for leishmaniasis. Thus, auranofin
      may represent a prototype drug that can be used to identify signaling pathways
      within the parasite and host cell critical for parasite growth and survival. 

PMID- 24328401
TI  - One-pot access to push-pull oligoenes by sequential [2 + 2] cycloaddition
      retroelectrocyclization reactions.
AB  - The formal [2 + 2] cycloaddition-retroelectrocyclization reaction was employed as
      the key transformation to obtain donor-substituted, pi-conjugated polycyanohexa
      1,3,5-trienes (TCHTs and PCHTs) and polycyanoocta-1,3,5,7-tetraenes from donor
      substituted tetracyanobuta-1,3-dienes (TCBDs) and electron-rich alkynes. These
      push-pull-substituted oligoene chromophores were also accessed in good yield from
      tetracyanoethylene and donor-substituted alkynes by using a one-pot protocol. All
      bis-(N,N-dialkylanilino) donor-substituted push-pull trienes and tetraenes showed
      better electron-accepting potency and lower HOMO-LUMO gaps than the corresponding
      TCBDs, as evidenced by optical and electrochemical studies. 

PMID- 24328402
TI  - Quartz crystal microbalance study of ionic strength and pH-dependent polymer
      conformation and protein adsorption/desorption on PAA, PEO, and mixed PEO/PAA
      brushes.
AB  - The conformation of polymer chains grafted on a substrate influences protein
      adsorption. In a previous study, adsorption/desorption of albumin was
      demonstrated on mixed poly(ethylene oxide) (PEO)/poly(acrylic acid) (PAA)
      brushes, triggered by solutions of adequate pH and ionic strength (I). In the
      present work, homolayers of PEO or PAA are submitted to saline solutions with pH
      from 3 to 9 and I from 10(-5) to 10(-1) M, and their conformation is evaluated in
      real time using quartz crystal microbalance with dissipation monitoring (QCM-D).
      Shrinkage/swelling of PAA chains and hydration and salt condensation in the brush
      are evidenced. The adsorption of human serum albumin (HSA) onto such brushes is
      also monitored in these different saline solutions, leading to a deep
      understanding of the influence of polymer chain conformation, modulated by pH and
      I, on protein adsorption. A detailed model of the conformation of PEO/PAA mixed
      brushes depending on pH and I is then proposed, providing a rationale for the
      identification of conditions for the successive adsorption and desorption of
      proteins on such mixed brushes. The adsorption/desorption of albumin on PEO/PAA
      is demonstrated using QCM-D. 

PMID- 24328403
TI  - Papillary lesions of indolent course: reducing the overdiagnosis of indolent
      papillary thyroid cancer and unnecessary treatment.

PMID- 24328405
TI  - Hepatic tumors: a continuous challenge to achieve further improvements.
AB  - Bucharest (Romania) hosted this year's annual meeting of the International
      Association of Surgeons, Gastroenterologists and Oncologists. The president of
      the Congress was Irinel Popescu of the University of Bucharest (Romania) and the
      meeting was held under the auspices of the International Association of Surgeons,
      Gastroenterologists and Oncologists president Masatoshi Makuuchi (Japanese Red
      Cross Medical Center, Tokyo, Japan) and its general secretary, Nicolas J
      Lygidakis (Athens Medical Center, Greece). The organizing committee of the
      Congress has made considerable efforts to promote the globalization of medical
      knowledge and to maintain the values of Medecins Sans Frontieres. The Congress
      was a model of scientific professionalism, and was attended by more than 850
      delegates. Approximately 250 specialists from 43 countries on five continents
      described their most recent advances, providing the delegates with an intense and
      very rich program. The program included symposia, video presentations, free
      papers and poster presentations. This article highlights the newest and most
      original results concerning the treatment of liver tumors, particularly in
      cirrhotic patients. 

PMID- 24328406
TI  - Sorafenib in squamous cell carcinoma of the head and neck: molecular basis and
      potential role.

PMID- 24328407
TI  - Preclinical and clinical development of afatinib: a focus on breast cancer and
      squamous cell carcinoma of the head and neck.
AB  - Aberrant signaling of the ErbB family of receptors plays an integral role in the
      tumorigenesis of many cancer types, including head and neck squamous cell
      carcinoma (HNSCC) and breast cancer (BC). Significant research efforts have
      focused on developing new treatments that target ErbB family members, with the
      last decade seeing the approval of small-molecule tyrosine kinase inhibitors and
      monoclonal antibodies that inhibit ErbB signaling. However, treatment resistance
      is an ever-growing problem and, therefore, new therapies are being investigated
      to overcome this hurdle. Afatinib is an irreversible ErbB family blocker that has
      demonstrated potent anti-tumor activity in preclinical models and has displayed
      clinical efficacy in patients with non-small-cell lung cancer, and activity in
      HNSCC and BC. Here, the preclinical and clinical development of afatinib in the
      treatment of non-small-cell lung cancer, HNSCC and BC is described in the context
      of currently approved agents.

PMID- 24328408
TI  - Prevalence and prognostic value of disseminated tumor cells in primary
      endometrial, cervical and vulvar cancer patients.
AB  - AIMS: Disseminated tumor cell (DTC) detection in bone marrow (BM) of primary
      breast cancer patients predicts poor prognosis. This study investigates the
      prevalence of DTCs and their prognostic significance in primary gynecologic
      malignancies. PATIENTS & METHODS: DTCs from BM aspirates of 603 patients with
      endometrial (311), cervical (228) and vulvar cancer (64) were identified by the
      pancytokeratin antibody A45B/B3. RESULTS: DTCs were detected in 18% of BM
      aspirates (21, 16 and 16% in endometrial, cervical and vulvar cancer,
      respectively). In cervical cancer, DTCs were associated with International
      Federation of Gynecology and Obstetrics stage, nodal status and lymphangiosis.
      There was no association between BM status and prognosis. CONCLUSION: Tumor cell
      dissemination is common in gynecological cancer. In contrast to breast cancer,
      DTCs that derive from cervical, endometrial or vulvar cancer have less potential
      to initiate metastatic regrow. The molecular mechanisms underlying this
      observation warrant further investigation.

PMID- 24328409
TI  - Correlation between the expression levels of miR-1 and PIK3CA in non-small-cell
      lung cancer and their relationship with clinical characteristics and prognosis.
AB  - AIMS: To examine the relationship between the expression levels of miR-1 and
      PIK3CA in resected non-small-cell lung cancer (NSCLC) tissues and clinical
      characteristics and prognosis. MATERIALS & METHODS: Levels of miR-1 and PIK3CA in
      cancerous and normal tissues obtained from 55 patients with NSCLC were measured
      by real-time PCR and western blot assays, and their associations with
      clinicopathological features were evaluated. RESULTS: A total of 69.1% of the
      NSCLC tissue samples showed low miR-1 expression (p < 0.05) and 70.9% showed high
      PIK3CA expression (p < 0.05). Patients with low miR-1 expression and those with
      high PIK3CA expression had significantly higher incidences of lymph node
      metastases and postoperative recurrences within 1 year after surgery than those
      with moderate miR-1 expression and moderate PIK3CA expression (p < 0.05 for
      both). CONCLUSION: Low expression of miR-1 and overexpression of PIK3CA in NSCLC
      tissues may be useful predictors of lymph node metastasis and postoperative
      recurrence in patients with NSCLC.

PMID- 24328410
TI  - Impact of anemia management with EPO on psychologic distress in cancer patients:
      results of a multicenter patient survey.
AB  - AIM: We investigated the role of erythropoietin (EPO) in reducing anemia and
      preventing the development of psychological distress in patients treated with
      chemotherapy. PATIENTS & METHODS: This prospective observational study enrolled
      591 adult patients receiving EPO at a dose of 30,000 IU administered once weekly
      for chemotherapy-induced anemia (mean baseline hemoglobin [Hb] level was 9.55
      g/dl) over a 12-month period. RESULTS: The majority of patients (371 [71%]
      patients) achieved a Hb increase >2 g/dl after 4 weeks of treatment.
      Interestingly, the nonresponder group had a statistically significant
      deterioration of their psychological conditions as indicated by psychological
      distress score (p = 0.01). However, within the group of responders to EPO, the
      Psychological Distress Inventory score remained unchanged. In the present study,
      severe side effects associated with EPO were not recorded. CONCLUSION: Hb
      increase, induced by EPO, ameliorates the psychological conditions of cancer
      patients.

PMID- 24328411
TI  - Role of immunotherapy in the treatment of advanced non-small-cell lung cancer.
AB  - After several decades of modest results with nonspecific immune stimulants,
      immunotherapy has become an exciting approach in the treatment of cancer.
      Although non-small-cell lung cancer has not been considered an immunogenic
      disease for very long, a better understanding of tumor immunology and the
      identification of new targets have led to the development of many clinical trials
      of immune-based therapies for this neoplasm. Promising results from many clinical
      trials suggest that immunotherapy could be an effective strategy in the
      management of advanced non-small-cell lung cancer. Further studies are required
      to help clinicians in the selection of patients who are more likely to benefit
      from immunotherapy strategies by the identification of biomarkers and to
      understand when the combination of immunotherapy with other agents should be
      recommended. 

PMID- 24328413
TI  - Photodynamic therapy: oncologic horizons.
AB  - Photodynamic therapy (PDT) is a light-based intervention with a long and
      successful clinical track record for both oncology and non-malignancies. In
      cancer patients, a photosensitizing agent is intravenously, orally or topically
      applied and allowed time to preferentially accumulate in the tumor region. Light
      of the appropriate wavelength and intensity to activate the particular
      photosensitizer employed is then introduced to the tumor bed. The light energy
      will activate the photosensitizer, which in the presence of oxygen should allow
      for creation of the toxic photodynamic reaction generating reactive oxygen
      species. The photodynamic reaction creates a cascading series of events including
      initiation of apoptotic and necrotic pathways both in tumor and neovasculature,
      leading to permanent lesion destruction often with upregulation of the immune
      system. Cutaneous phototoxicity from unintentional sunlight exposure remains the
      most common morbidity from PDT. This paper will highlight current research and
      outcomes from the basic science and clinical applications of oncologic PDT and
      interpret how these findings may lead to enhanced and refined future PDT.

PMID- 24328412
TI  - Metabolism and transport of tamoxifen in relation to its effectiveness: new
      perspectives on an ongoing controversy.
AB  - Tamoxifen reduces the rate of breast cancer recurrence by approximately a half.
      Tamoxifen is metabolized to more active metabolites by enzymes encoded by
      polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen is a
      substrate for ATP-binding cassette transporter proteins. We review tamoxifen's
      clinical pharmacology and use meta-analyses to evaluate the clinical epidemiology
      studies conducted to date on the association between CYP2D6 inhibition and
      tamoxifen effectiveness. Our findings indicate that the effect of both drug
      induced and/or gene-induced inhibition of CYP2D6 activity is likely to be null or
      small, or at most moderate in subjects carrying two reduced function alleles.
      Future research should examine the effect of polymorphisms in genes encoding
      enzymes in tamoxifen's complete metabolic pathway, should comprehensively
      evaluate other biomarkers that affect tamoxifen effectiveness, such as the
      transport enzymes, and focus on subgroups of patients, such as premenopausal
      breast cancer patients, for whom tamoxifen is the only guideline endocrine
      therapy.

PMID- 24328414
TI  - Isolation and amplification of mRNA within a simple microfluidic lab on a chip.
AB  - The major modules for realizing molecular biological assays in a micro-total
      analysis system (MUTAS) were developed for the detection of pathogenic organisms.
      The specific focus was the isolation and amplification of eukaryotic mRNA within
      a simple, single-channel device for very low RNA concentrations that could then
      be integrated with detection modules. The hsp70 mRNA from Cryptosporidium parvum
      was used as a model analyte. Important points of study were surface chemistries
      within poly(methyl methacrylate) (PMMA) microfluidic channels that enabled
      specific and sensitive mRNA isolation and amplification reactions for very low
      mRNA concentrations. Optimal conditions were achieved when the channel surface
      was carboxylated via UV/ozone treatment followed by the immobilization of
      polyamidoamine (PAMAM) dendrimers on the surface, thus increasing the
      immobilization efficiency of the thymidine oligonucleotide, oligo(dT)25, and
      providing a reliable surface for the amplification reaction, importantly, without
      the need for blocking agents. Additional chemical modifications of the remaining
      active surface groups were studied to avoid nonspecific capturing of nucleic
      acids and hindering of the mRNA amplification at low RNA concentrations.
      Amplification of the mRNA was accomplished using nucleic acid sequence-based
      amplification (NASBA), an isothermal, primer-dependent technique. Positive
      controls consisting of previously generated NASBA amplicons could be diluted
      10(15) fold and still result in successful on-chip reamplification. Finally, the
      successful isolation and amplification of mRNA from as few as 30 C. parvum
      oocysts was demonstrated directly on-chip and compared to benchtop devices. This
      is the first proof of successful mRNA isolation and NASBA-based amplification of
      mRNA within a simple microfluidic device in relevant analytical volumes. 

PMID- 24328415
TI  - Efficacy and safety of the adjustable gastric band - pooled interim analysis of
      the APEX and HERO studies at 48 weeks.
AB  - OBJECTIVE: This 48 week combined analysis reports safety and clinical
      effectiveness of the LAP-BAND AP * laparoscopic adjustable gastric band (LAGB) in
      severely obese patients enrolled in the 5 year, prospective, observational, open
      label APEX (NCT00501085) and HERO (NCT00953173) studies. METHODS: The studies
      enrolled 1620 patients (APEX: N = 514; HERO: N = 1106), 1140 patients in the US
      (including all APEX patients), and 480 patients in the European Union (EU),
      Canada or Australia. APEX and HERO are non-randomized, non-comparator, open-label
      studies with differences in study management practices and follow-up. Notably,
      laboratory data were not collected during the APEX study. RESULTS: After 48
      weeks, mean (SD) percentage weight loss (%WL) was for APEX: 18.7% (7.9); HERO-US:
      17.9% (8.5); HERO-EU: 16.5% (10.3); HERO-Canada: 13.4% (8.9); and HERO-Australia:
      12.3% (6.9). After 48 weeks, there were no significant differences in %WL for
      APEX vs. HERO-US. After 48 weeks in the combined analysis (APEX + HERO): (1)
      patients without vs. with type 2 diabetes at baseline had greater %WL (18% [8.7]
      vs. 16% [8.5], p = 0.002); (2) female patients had greater %WL vs. male patients
      (17.9% [8.5] vs. 15.9% [9.3], p = 0.003); (3) younger patients had greater %WL
      vs. older patients (<50 years: 17.8% [8.7] vs. >=50 years: 16.7% [8.6], p =
      0.035); (4) baseline BMI did not affect %WL (<=35 to <=45 kg/m(2): 17.7% [8.4]
      vs. >45 kg/m(2): 17.1% [9.1], p = 0.272). Device-related serious adverse events
      and adverse events were reported in 1.9% and 17.7% of patients, respectively.
      Revision and explantation surgeries were carried out on 3.4% and 2.3% of
      patients, respectively during the 48 weeks of follow-up. CONCLUSIONS: This
      analysis demonstrates the effective weight loss and safety profile of the current
      LAGB system, with US patients achieving better weight loss than patients from
      outside the US.

PMID- 24328416
TI  - Greater age-related decline in markers of physical, mental and cognitive health
      among Israeli older adults exposed to lifetime cumulative adversity.
AB  - OBJECTIVES: This longitudinal investigation addressed whether and how lifetime
      cumulative adversity and depressive symptoms moderated age-related decline in
      markers of physical, mental, and cognitive health. METHOD: 1248 older adults
      (mean age = 62 at Wave 1) who completed the first two waves of the Israeli
      component of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel)
      reported on exposure to potentially traumatic life events, depressive symptoms,
      and three outcomes - disability, quality of life, and cognitive markers. RESULTS:
      Age was related to greater functional decline in outcome measures across the two
      waves (i.e., increase in disability and decrease in quality of life and cognitive
      functioning). This age-related decline became stronger as lifetime adversity
      increased. A three-way interaction showed that the greatest age-related
      functional decline in outcome measures was especially salient among those with
      high level of lifetime adversity and high level of depressive symptoms.
      CONCLUSION: Lifetime cumulative adversity is associated with a more noticeable
      process of age-related dysfunction across various markers of health. Although the
      majority of older adults are resilient to lifetime adversity, prevention and
      intervention programs should be aimed at mitigating the pronounced senescence
      observed when adversity accumulated to a large degree, and especially when it is
      accompanied with high level of distress.

PMID- 24328417
TI  - A Lys-Trp cation-pi interaction mediates the dimerization and function of the
      chloride intracellular channel protein 1 transmembrane domain.
AB  - Chloride intracellular channel protein 1 (CLIC1) is a dual-state protein that can
      exist either as a soluble monomer or in an integral membrane form. The
      oligomerization of the transmembrane domain (TMD) remains speculative despite it
      being implicated in pore formation. The extent to which electrostatic and van der
      Waals interactions drive folding and association of the dimorphic TMD is unknown
      and is complicated by the requirement of interactions favorable in both aqueous
      and membrane environments. Here we report a putative Lys37-Trp35 cation-pi
      interaction and show that it stabilizes the dimeric form of the CLIC1 TMD in
      membranes. A synthetic 30-mer peptide comprising a K37M TMD mutant was examined
      in 2,2,2-trifluoroethanol, sodium dodecyl sulfate micelles, and 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine liposomes using far-ultraviolet (UV) circular
      dichroism, fluorescence, and UV absorbance spectroscopy. Our data suggest that
      Lys37 is not implicated in the folding, stability, or membrane insertion of the
      TMD peptide. However, removal of this residue impairs the formation of dimers and
      higher-order oligomers. This is accompanied by a 30-fold loss of chloride influx
      activity, suggesting that dimerization modulates the rate of chloride
      conductance. We propose that, within membranes, individual TMD helices associate
      via a Lys37-mediated cation-pi interaction to form active dimers. The latter
      findings are also supported by results of modeling a putative TMD dimer
      conformation in which Lys37 and Trp35 form cation-pi pairs at the dimer
      interface. Dimeric helix bundles may then associate to form fully active ion
      channels. Thus, within a membrane-like environment, aromatic interactions
      involving a polar lysine side chain provide a thermodynamic driving force for
      helix-helix association. 

PMID- 24328418
TI  - Influence of charge on encapsulation and release behavior of small molecules in
      self-assembled layer-by-layer microcapsules.
AB  - The objective of this study is to investigate the influence of charge of model
      small molecules on their encapsulation and release behavior in layer-by-layer
      microcapsules (LbL-MC). Poly(styrene sulfonate) and poly(ethylene imine) were
      sequentially adsorbed on calcium carbonate sacrificial templates to prepare LbL
      MC. Model molecules with varying charge, anionic - ascorbic acid, cationic -
      imatinib mesylate (IM) and neutral - 5-fluorouracil were encapsulated in LbL-MC.
      Free and encapsulated LbL-MC were characterized using zetasizer, FTIR
      spectroscope and differential scanning calorimeter. The influence of IM-loaded
      LbL-MC on cell viability was studied in B16F10 murine melanoma cells.
      Furthermore, biodistribution of IM-loaded LbL-MC with and without PEGylation was
      studied in BALB/c mice. Results showed spherical LbL-MC of 3.0 +/- 0.4 MUm
      diameter. Encapsulation efficiency of LbL-MC increased linearly (R(2 )= 0.89
      0.99) with the increase in solute concentration. Increase in pH from 2 to 6
      increased the encapsulation of charged molecules in LbL-MC. Charged molecules
      showed greater encapsulation efficiency in LbL-MC compared with neutral molecule.
      In vitro release kinetics showed Fickian and non-Fickian diffusion of small
      molecules, depending on the nature of molecular interactions with LbL-MC. At 50
      MUM concentration, free IM showed significantly (p < 0.05) more cytotoxicity
      compared with IM-loaded LbL-MC. Biodistribution studies showed that PEGylation of
      LbL-MC decreased the liver and spleen uptake of IM-encapsulated LbL-MC. In
      conclusion, LbL-MC can be developed as a potential carrier for small molecules
      depending on their physical and chemical properties.

PMID- 24328419
TI  - Polymorphisms in TSHR and IL1RN genes and the risk and prognosis of Hashimoto's
      thyroiditis.
AB  - Hashimoto's thyroiditis (HT) is a complex genetic autoimmune thyroid disease
      (AITD). Thyroid-stimulating hormone receptor (TSHR) is considered as candidate
      gene in AITD. IL1RN gene is involved in the pathogenesis of a number of
      autoimmune diseases. These findings prompted us to investigate the association of
      TSHR and IL1RN genes polymorphism with the risk and the prognosis of HT in
      Tunisia. A total of 249 healthy controls and 202 patients with HT were genotyped
      for TSHR D727E and IL1RN(VNTR) polymorphism. No significant difference was found
      for D727E polymorphism between HT patients and healthy controls. For IL1RN gene,
      we found an association between HT and IL1RN(VNTR) polymorphism. The A1A3
      genotype was more prevalent in HT patients than in controls. However, the A1A4
      genotype was associated with HT as a protective factor. Significant association
      of the TSHR polymorphism with lower plasma TSH level in HT patients has been
      detected. We found for the first time an association of IL1RN(VNTR) polymorphism
      with the production of anti-thyroid peroxidase antibody at the onset of disease.
      These preliminary results suggest that only the IL1RN(VNTR) polymorphism may be
      associated with HT susceptibility and that TSHR and IL1RN(VNTR) polymorphisms may
      represent prognostic factors for predicting the severity of HT.

PMID- 24328420
TI  - Effectiveness of inhaled corticosteroids in the treatment of acute asthma in
      children in the emergency department: a meta-analysis.
AB  - OBJECTIVES: This meta-analysis aimed to compare the treatment of an acute asthma
      attack in children in the emergency department (ED) with inhaled corticosteroids
      (ICS) versus placebo or oral systemic corticosteroids (SC) as assessed by the
      hospital admission rates. METHODS: After searching Medline, Cochrane, EMBASE, and
      Google Scholar, we identified ten articles that described randomized controlled
      trials of ICS versus placebo or oral SC for treating children with asthma attacks
      in the ED. Primary outcome was the hospital admission rate as defined as
      inpatient admission or admission into intensive care unit. RESULTS: Across the
      studies, a range of drugs and doses were used. For ICS, six studies administered
      budesonide (dose range: 0.4-2 mg), and three studies gave fluticasone/flunisolide
      (dose range: 0.5-2 mg). Six studies administered oral prednisone (dose range: 1-2
      mg/kg/day), and four studies gave placebo. The rate of hospital admissions in
      patients treated with ICS was not significantly higher than those treated with
      oral SC. The rate of hospital admissions in patients treated with ICS was
      significantly lower than those treated with placebo. CONCLUSION: ICS treatment of
      children with acute asthma exacerbations showed a similar rate of hospitalization
      as those treated by SC.

PMID- 24328421
TI  - Adiponectin, interleukin-6, and endothelin-1 correlate with modifiable
      cardiometabolic risk factors in overweight/obese men.

PMID- 24328422
TI  - Iodine-catalyzed regioselective 2-sulfonylation of indoles with sodium
      sulfinates.
AB  - Iodine-catalyzed selective 2-arylsulfonyl indole formation from indoles and
      sodium sulfinates is disclosed. Various substituted 2-arylsulfonyl indoles were
      obtained in one pot in the absence of metal catalyst at room temperature under
      air. 

PMID- 24328423
TI  - Ninety minutes to die.

PMID- 24328424
TI  - Vogt-Koyanagi-Harada disease: clinical and demographic characteristics of
      patients in a specialized eye hospital in Turkey.
AB  - PURPOSE: To evaluate clinical and demographic features of Vogt-Kayanagi-Harada
      disease (VKH) disease in Turkish patients and compare them with previously
      published data. METHODS: Demographic and clinical features of 32 patients
      diagnosed as VKH in a tertiary referral center were retrospectively reviewed.
      RESULTS: The mean age at presentation was 33.6 +/- 10.4 years. Seventy-five
      percent of the patients were female and 62.5% of the patients presented during
      the last 2 years. The disease was complete in 31.2%, incomplete in 50%, and
      probable in 18.8% of the patients. The clinical course was acute in 50%, chronic
      recurrent in 34.4%, and chronic in 15.6%. The most common findings were bilateral
      serous retinal detachment +/- papillitis in acute cases and retinal pigment
      epithelial changes of the macula in chronic cases. CONCLUSIONS: Although rare in
      Turkey, VKH disease seems to have increased during the last few years. The
      disease is incomplete and acute in half of the patients and has a quite good
      visual prognosis.

PMID- 24328425
TI  - Fractal water quality fluctuations spanning the periodic table in an intensively
      farmed watershed.
AB  - Recently developed measurement technologies can monitor surface water quality
      almost continuously, creating high-frequency multiparameter time series and
      raising the question of how best to extract insights from such rich data sets.
      Here we use spectral analysis to characterize the variability of water quality at
      the AgrHys observatory (Western France) over time scales ranging from 20 min to
      12 years. Three years of daily sampling at the intensively farmed Kervidy-Naizin
      watershed reveal universal 1/f scaling for all 36 solutes, yielding spectral
      slopes of 1.05 +/- 0.11 (mean +/- standard deviation). These 36 solute
      concentrations show varying degrees of annual cycling, suggesting different
      controls on watershed export processes. Twelve years of daily samples of SO4,
      NO3, and dissolved organic carbon (DOC) show that 1/f scaling does not continue
      at frequencies below 1/year in those constituents, whereas a 12-year daily record
      of Cl shows a general 1/f trend down to the lowest measurable frequencies.
      Conversely, approximately 12 months of 20 min NO3 and DOC measurements show that
      at frequencies higher than 1/day, the spectra of these solutes steepen to slopes
      of roughly 3, and at time scales shorter than 2-3 h, the spectra flatten to
      slopes near zero, reflecting analytical noise. These results confirm and extend
      the recent discovery of universal fractal 1/f scaling in water quality at the
      relatively pristine Plynlimon watershed in Wales, further demonstrating the
      importance of advective-dispersive transport mixing in catchments. However, the
      steeper scaling at subdaily time scales suggests additional short-term damping of
      solute concentrations, potentially due to in-stream or riparian processes. 

PMID- 24328426
TI  - Arctic Ocean: is it a sink or a source of atmospheric mercury?
AB  - High levels of mercury in marine mammals threaten the health of Arctic
      inhabitants. Whether the Arctic Ocean (AO) is a sink or a source of atmospheric
      mercury is unknown. Given the paucity of observations in the Arctic, models are
      useful in addressing this question. GEOS-Chem and GRAHM, two complex numerical
      mercury models, present contrasting pictures of atmospheric mercury input to AO
      at 45 and 108 Mg yr(-1), respectively, and ocean evasion at 90 and 33 Mg yr(-1),
      respectively. We provide a comprehensive evaluation of GRAHM simulated
      atmospheric mercury input to AO using mercury observations in air, precipitation
      and snowpacks, and an analysis of the discrepancy between the two modeling
      estimates using observations. We discover two peaks in high-latitude summertime
      concentrations of atmospheric mercury. We show that the first is caused mainly by
      snowmelt revolatilization and the second by AO evasion of mercury. Riverine
      mercury export to AO is estimated at 50 Mg yr(-1) based on measured DOC export
      and at 15.5-31 Mg yr(-1) based on simulated mercury in meltwater. The range of
      simulated mercury fluxes to and from AO reflects uncertainties in modeling
      mercury in the Arctic; comprehensive observations in all compartments of the
      Arctic ecosystem are needed to close the gap. 

PMID- 24328427
TI  - Differential upregulation of human 2'5'OAS genes on systemic sclerosis: Detection
      of increased basal levels of OASL and OAS2 genes through a qPCR based assay.
AB  - 2'5'OAS are template-independent RNA polymerases with antiviral activity and
      important to homeostasis maintenance. Here we have developed quantitative PCR
      (qPCR) reactions for the detection of each individual 2'5'OAS human gene and used
      them to evaluate these gene levels in systemic sclerosis patients cells. The
      method was efficient for quantification of 2'5'OAS genes on human cells after
      interferon (IFN) treatment, and revealed that primary cells from patients with
      systemic sclerosis have increased basal levels of OASL and OAS2 genes. When
      treated, patients cells are able to induce all four 2'5'OAS genes. Our hypothesis
      is that abnormally circulating type I IFNs on the disease could be establishing a
      desensitized state on patients cells, making them refractory to subsequent IFN
      doses, and that OASL and OAS2 genes upregulation may be due to an IFN-independent
      stimulus. Further characterizing the biological activities of these genes, their
      induction pathways and their regulatory functions can lead to better
      understanding of systemic sclerosis molecular mechanisms and of their biological
      activities.

PMID- 24328428
TI  - Interactions at the silica-peptide interface: the influence of particle size and
      surface functionality.
AB  - The variety of interactions that can occur at the silica/aqueous interface makes
      silica nanoparticles (SiNPs) attractive materials for technological applications.
      Despite their importance, interfacial interactions are not fully understood. In
      this contribution, we investigate the effect of (1) particle size and (2) surface
      functionalization on the adsorption of small biomolecular binders on SiNPs. Small
      silica binding peptides with different properties (charge, pI, and amino acid
      composition) were used as binders, while a range of fully characterized SiNPs of
      diameters ranging between 28 and 500 nm (pristine silica) and SiNPs of ca. 500 nm
      functionalized with cationic 3-aminopropyl groups and hydrophobic methyl groups
      was used as binding substrates. Adsorption and binding affinity were investigated
      by a fluorimetric assay at pH 7.4. A detailed characterization of the surface
      chemistry of the particles showed that the extent of surface functionalization on
      modified silica was well below monolayer coverage [by X-ray photoelectron
      spectroscopy (XPS), ca. 2 and 18 atomic % for the amino- and methyl-modified
      surfaces, respectively]. Although peptide binding is generally moderated by the
      physicochemical characteristics of the adsorbing peptide, the introduction of
      such a small degree of functionality onto silica particles was sufficient to
      produce drastic changes in adsorption at the silica/aqueous interface. In
      addition, an increase in peptide adsorption with an increasing particle size,
      independent of the nature and properties of the peptide, was observed. This
      particle size effect is attributed to a shift of the dominant binding mechanism
      toward electrostatic interactions on larger SiNPs. The data presented demonstrate
      that particle size and surface functionality are both parameters that can
      substantially influence (bio)molecule uptake via modulation or selection of
      specific binding modes at the silica/peptide interface. These results are
      applicable to the design and development of interfaces with specific
      adsorption/affinity response for biomedical applications, where uptake is
      important, such as drug delivery. Further, they provide important insights on how
      peptide affinity and selection during biopanning can be determined by small
      changes in surface chemistry of the surface of a target that can, in some
      instances, be associated with the presence of impurities. 

PMID- 24328429
TI  - Real-life efficacy and safety of vildagliptin compared with sulfonylureas as add
      on to metformin in patients with type 2 diabetes mellitus in Germany.
AB  - OBJECTIVE: Metformin is an established first-line treatment for type 2 diabetes
      mellitus (T2DM) patients, but intensification of oral anti-diabetes therapy is
      usually required over time. A large observational study of 45,868 T2DM patients
      in 27 countries (EDGE) was conducted to compare the effectiveness and safety of
      vildagliptin as add-on therapy to another oral anti-diabetes drug (OAD) vs other
      dual OAD combinations. This report presents results from a post-hoc analysis of
      patients in Germany who received vildagliptin or a sulfonylurea (SU) in
      combination with metformin. RESEARCH DESIGN AND METHODS: Patients inadequately
      controlled with monotherapy became eligible only after the add-on treatment was
      finalized. Patients included were assigned to receive either vildagliptin or
      another OAD (SUs, thiazolidinediones, glinides, alpha-glucosidase inhibitors, or
      metformin; DPP-4 inhibitors or glucagon-like peptide-1 [GLP-1] mimetics/analogs
      were excluded). The primary end-point was the proportion of patients achieving a
      reduction in HbA1c >0.3% without peripheral edema, hypoglycemia, discontinuation
      due to gastrointestinal event, or weight gain >=5%. RESULTS: Of 8887 patients
      enrolled in Germany, 6439 received vildagliptin and 971 received SUs as add-on to
      metformin. The primary end-point was reached in 34.9% and 29.6% of patients in
      the vildagliptin and SU groups, respectively, with an unadjusted odds ratio of
      1.27 (95% CI = 1.09, 1.47; p = 0.001). HbA1c decreased in both cohorts from
      baseline (-0.7% with vildagliptin vs -0.5% with SUs), with a mean between-group
      difference of -0.2% (95% CI = -0.22, -0.09). The number of hypoglycemic events
      was 4-fold higher in the SU group than in the vildagliptin group (vildagliptin =
      0.11%; SU = 0.41%). CONCLUSIONS: In a real-life setting, vildagliptin was
      associated with a numerically greater reduction in HbA1c, less hypoglycemia, and
      more patients reaching target HbA1c without hypoglycemia or weight gain compared
      with SUs. Open-label design and under reporting of adverse events are limitations
      of this post hoc analysis.

PMID- 24328430
TI  - Modern supercritical fluid technology for food applications.
AB  - This review provides an update on the use of supercritical fluid (SCF) technology
      as applied to food-based materials. It advocates the use of the solubility
      parameter theory (SPT) for rationalizing the results obtained when employing sub-
      and supercritical media to food and nutrient-bearing materials and for optimizing
      processing conditions. Total extraction and fractionation of foodstuffs employing
      SCFs are compared and are illustrated by using multiple fluids and unit processes
      to obtain the desired food product. Some of the additional prophylactic benefits
      of using carbon dioxide as the processing fluid are explained and illustrated
      with multiple examples of commercial products produced using SCF media. I
      emphasize the role of SCF technology in the context of environmentally benign and
      sustainable processing, as well as its integration into an overall biorefinery
      concept. Conclusions are drawn in terms of current trends in the field and future
      research that is needed to secure new applications of the SCF platform as applied
      in food science and technology. 

PMID- 24328431
TI  - From Tomato King to World Food Prize laureate.
AB  - This autobiographical article describes my early years, education, and career at
      Purdue University. Helping form and expand the Department of Food Science at
      Purdue was exciting and gratifying, and working with students in the classroom
      and on research projects was rewarding and kept me feeling young. My research on
      bulk aseptic processing allowed me to help solve problems relevant to the tomato
      industry, but I learned later that it had much broader relevance. I certainly
      never expected the impact and visibility of the work to result in my being
      awarded the World Food Prize. Being the first food scientist to win this award
      has enabled me to focus increased attention on the need to reduce food losses. 

PMID- 24328432
TI  - Delivery of lipophilic bioactives: assembly, disassembly, and reassembly of lipid
      nanoparticles.
AB  - The oral bioavailability of lipophilic bioactive molecules can be greatly
      increased by encapsulating them within engineered lipid nanoparticles (ELNs),
      such as micelles, microemulsions, nanoemulsions, or solid lipid nanoparticles
      (SLNs). After ingestion, these ELNs are disassembled in the gastrointestinal
      tract (GIT) and then reassembled into biological lipid nanoparticles (mixed
      micelles) in the small intestine. These mixed micelles solubilize and transport
      lipophilic bioactive components to the epithelial cells. The mixed micelles are
      then disassembled and reassembled into yet another form of biological lipid
      nanoparticle [chylomicrons (CMs)] within the enterocyte cells. The CMs carry the
      bioactive components into the systemic (blood) circulation via the lymphatic
      system, thereby avoiding first-pass metabolism. This article provides an overview
      of the various physicochemical and physiological processes responsible for the
      assembly and disassembly of lipid nanoparticles outside and inside the GIT. This
      knowledge can be used to design food-grade delivery systems to improve the oral
      bioavailability of encapsulated lipophilic bioactive components. 

PMID- 24328433
TI  - The experience of couples when one partner has a stroke at a young age: an
      interpretative phenomenological analysis.
AB  - PURPOSE: Stroke is a major cause of disability worldwide and affects a
      significant number of working age adults each year. The consequences of stroke
      impact upon both young stroke survivors and their partners and this study aimed
      to qualitatively explore their joint experience. METHODS: Eight joint semi
      structured interviews were conducted and analysed using IPA. RESULTS: Three
      themes were identified: (1) "How's this happened?"--Making sense of the stroke;
      (2) "Is this what life is going to be like now?"--From partners to carer and
      "cared for"; (3) "I lost being a man. I was a little boy, being looked after all
      the time"--From partners to parent and child. CONCLUSIONS: Stroke at a young age
      can significantly disrupt couples' life biographies. The findings highlight the
      need for both partners to adapt to their reciprocal relationship role changes and
      the importance of addressing the couple as a focus for intervention. Implications
      for Rehabilitation Stroke at a young age is an abrupt event that impacts upon
      both partners in a relationship. The findings add insight to some of the issues
      faced by young stroke survivors and their partners, which can now be considered
      in tailoring treatment to this specific cohort within the context of services
      predominated by older adults. The findings highlight significant relationship
      role changes experienced within couples, which suggests a need for rehabilitation
      interventions to focus on the adjustment of both partners.

PMID- 24328434
TI  - Metallosupramolecular poly[2]pseudorotaxane constructed by metal coordination and
      crown-ether-based molecular recognition.
AB  - A novel bis(m-phenylene)-32-crown-10 derivative bearing two pi-extended pyridyl
      groups was synthesized, and its host-guest complexation with a paraquat
      derivative to form a threaded [2]pseudorotaxane was studied. Subsequently, a
      poly[2]pseudorotaxane was constructed with a metallosupramolecular polymer
      backbone via metal coordination, which was comprehensively confirmed by the
      combination of (1)H NMR, (31)P{(1)H} NMR, DOSY NMR, DLS, and EDX techniques. 

PMID- 24328436
TI  - Fourth cranial nerve palsy and bilateral acute retinal necrosis following human
      herpesvirus 6 infection of the central nervous system.
AB  - Acute retinal necrosis (ARN) is a rare, potentially blinding condition typically
      affecting immunocompetent individuals. It is defined by the clinical triad of
      vitreous inflammation, occlusive vasculopathy, and progressive retinal necrosis,
      usually located in peripheral retina with circumferential extension. Varicella
      zoster virus (VZV), herpes simplex virus (HSV), Epstein-Barr virus (EBV) and
      occasionally cytomegalovirus (CMV) are the common causative agents of ARN.
      Reports of human herpesvirus 6 (HHV6) infection of the central nervous system
      (CNS) associated with ocular inflammatory disease are extremely rare. We here
      report the case of a 22-year-old immunocompetent male who presented with acute
      bilateral ARN and fourth nerve palsy, following HHV6 infection of the CNS and EBV
      infectious mononucleosis.

PMID- 24328435
TI  - Perceived Cognitive Impairment among African American elders: health and
      functional impairments in daily life.
AB  - OBJECTIVES: The Center for Disease Control began to assess Perceived Cognitive
      Impairment in 2009, yet there has been no in-depth study of how perceived decline
      in thinking or memory skills may be associated to the health and lifestyle of an
      independent community-dwelling older person. Among urban-dwelling older African
      Americans who are at elevated risk for cognitive impairment and dementia, we know
      even less regarding the interaction of these risk factors. METHOD: Five hundred
      and one African American elders (n=501) between the ages of 55 and 95 with an
      average age of 70.73 years (SD=8.6 years) participated in telephone interviews.
      RESULTS: Approximately one-third of the elders reported that their memory,
      thinking skills, or ability to reason was worse than a year ago (n=150; 29.9%)
      and 25% of this group (n=38) reported that this Perceived Cognitive Impairment
      impacted their daily activities and/or warranted a consultation with their
      doctor. Bivariate analyses indicated that Perceived Cognitive Impairment was
      associated with increased health problems, mobility limitations, depressed mood,
      and lower social functioning. CONCLUSION: Elders who reported that cognitive
      problems impacted their daily functioning reported the greatest health and mental
      health problems. Perceived Cognitive Impairment is an important health variable
      with implications for an older adult's overall health, mobility, and mental
      health.

PMID- 24328437
TI  - Fat-soluble nutraceuticals and their composition in heat-processed wheat germ and
      wheat bran.
AB  - Nutraceuticals availability in heat-processed foods is considered to be the index
      for healthy food. This study has made an attempt to optimize the temperature to
      retain nutraceuticals in wheat bran (WB) and wheat germ (WG). Heated WG (130 
      degrees C & 140  degrees C) and WB (140  degrees C & 150  degrees C) were
      analyzed for sensory profiles. Extracted oils were subjected to physicochemical
      parameter as well as its nutraceuticals. Increased oil yield, color values and
      reduced free fatty acids were found with varied temperatures. Fat-soluble
      compounds total tocols, steryl ferulates and carotenoids found in WG (0.316,
      0.058 and 0.011%) and WB (0.228, 0.595 and 0.015%) and maximum reductions started
      in WG (0.183%, 0.034% and 0.004%) at 130  degrees C. The free radical-scavenging
      activities of control samples showed high EC50 values than processed samples;
      however, no differences were observed between two temperatures. Study may clearly
      spell out that the reduced nutraceuticals observed after subjecting food raw
      materials to optimum temperature eventually lead to its quality.

PMID- 24328439
TI  - For an influenza vaccine, are two Bs better than one?

PMID- 24328438
TI  - Sexual behaviors and sexually transmitted infections in a nationally
      representative sample of women veterans and nonveterans.
AB  - BACKGROUND: Women veterans are a growing population with unique characteristics
      and documented health disparities. Few studies have examined their sexual
      behaviors and rates of sexually transmitted infections (STIs), and none have
      compared women veterans to nonveterans to identify potential sexual health
      disparities. METHODS: We used data from the 1999-2010 National Health and
      Nutrition Examination Survey, a nationally representative U.S. survey. We
      compared lifetime sexual history (age at first intercourse, number of partners),
      sexual activity in the last year, and STIs between women veterans (n=151) and
      nonveterans (n=8738), adjusting for age, race/ethnicity, education, marital
      status, binge drinking, and survey year. RESULTS: Compared to nonveterans, women
      veterans reported a younger age at first intercourse and a greater number of
      female and male lifetime sexual partners, and they were more likely to have ever
      had sex with a woman. They were also more likely than nonveterans to have genital
      herpes and genital warts. CONCLUSIONS: Women veterans reported higher rates of
      sexual activity and STIs than nonveterans. Future research is needed to assess
      high-risk behaviors and determine what factors may underlie these associations.
      Providers should ensure thorough screening and intervention services are provided
      for this growing population.

PMID- 24328440
TI  - Improving value in Medicare with an SGR fix.

PMID- 24328441
TI  - Implementing Obamacare in a red state--dispatch from North Carolina.

PMID- 24328442
TI  - Contraception at risk.

PMID- 24328443
TI  - Hospital industry consolidation--still more to come?

PMID- 24328444
TI  - Vaccine for prevention of mild and moderate-to-severe influenza in children.
AB  - BACKGROUND: Commonly used trivalent vaccines contain one influenza B virus
      lineage and may be ineffective against viruses of the other B lineage. We
      evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine
      (QIV) containing both B lineages. METHODS: In this multinational, phase 3,
      observer-blinded study, we randomly assigned children 3 to 8 years of age, in a
      1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end
      point was influenza A or B confirmed by real-time polymerase chain reaction (rt
      PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza
      and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the
      effect of vaccination on daily activities and utilization of health care
      resources were assessed in the total vaccinated cohort (2584 children in each
      group) and the per-protocol cohort (2379 children in the QIV group and 2398 in
      the control group). RESULTS: In the total vaccinated cohort, 62 children in the
      QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed
      influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI],
      45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5%
      CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack
      rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control
      group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per
      protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the
      efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the
      efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI,
      47.1 to 86.3). The QIV was associated with reduced risks of a body temperature
      above 39 degrees C and lower respiratory tract illness, as compared with the
      control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to
      0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic
      against all four strains. Serious adverse events occurred in 36 children in the
      QIV group (1.4%) and in 24 children in the control group (0.9%). CONCLUSIONS: The
      QIV was efficacious in preventing influenza in children. (Funded by
      GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT01218308.).

PMID- 24328445
TI  - State-to-state spectroscopy and dynamics of ions and neutrals by photoionization
      and photoelectron methods.
AB  - Recent advances in high-resolution photoionization, photoelectron, and
      photodissociation studies based on single-photon vacuum ultraviolet (VUV) and two
      color infrared (IR)-VUV, visible (Vis)-ultraviolet (UV), and VUV-VUV laser
      excitations are illustrated with selected examples. VUV laser photoionization
      coupled with velocity-map-imaging threshold photoelectron (VMI-TPE) detection can
      achieve comparable energy resolution but has higher-detection sensitivities than
      those observed in VUV laser pulsed field ionization photoelectron (PFI-PE)
      measurements. For molecules with known intermediate states, IR-VUV and Vis-UV
      excitation schemes are highly sensitive for rovibronically selected and resolved
      PFI-PE studies. The successful applications of the VUV-PFI-PE, VUV-VMI-TPE, and
      Vis-UV-PFI-PE methods to state-resolved and state-to-state photoelectron studies
      of transient radicals and transitional metal-containing molecules are
      highlighted. The most recently established VUV-VUV pump-probe time-slice VMI
      photoion method is shown to be promising for state-to-state photodissociation
      studies of small molecules relevant to planetary atmospheres and for the
      fundamental understanding of photodissociation dynamics. 

PMID- 24328446
TI  - Imaging fluorescence fluctuation spectroscopy: new tools for quantitative
      bioimaging.
AB  - Fluorescence fluctuation spectroscopy (FFS) techniques provide information at the
      single-molecule level with excellent time resolution. Usually applied at a single
      spot in a sample, they have been recently extended into imaging formats, referred
      to as imaging FFS. They provide spatial information at the optical diffraction
      limit and temporal information in the microsecond to millisecond range. This
      review provides an overview of the different modalities in which imaging FFS
      techniques have been implemented and discusses present imaging FFS capabilities
      and limitations. A combination of imaging FFS and nanoscopy would allow one to
      record information with the detailed spatial information of nanoscopy, which is
      ~20 nm and limited only by fluorophore size and labeling density, and the time
      resolution of imaging FFS, limited by the fluorescence lifetime. This combination
      would provide new insights into biological events by providing spatiotemporal
      resolution at unprecedented levels. 

PMID- 24328447
TI  - Ion mobility analysis of molecular dynamics.
AB  - The combination of mass spectrometry and ion mobility spectrometry (IMS)
      employing a temperature-variable drift cell or a drift tube divided into sections
      to make IMS-IMS experiments possible allows information to be obtained about the
      molecular dynamics of polyatomic ions in the absence of a solvent. The
      experiments allow the investigation of structural changes of both activated and
      native ion populations on a timescale of 1-100 ms. Five different systems
      representing small and large, polar and nonpolar molecules, as well as
      noncovalent assemblies, are discussed in detail: a dinucleotide, a sodiated
      polyethylene glycol chain, the peptide bradykinin, the protein ubiquitin, and two
      types of peptide oligomers. Barriers to conformational interconversion can be
      obtained in favorable cases. In other cases, solution-like native structures can
      be observed, but care must be taken in the experimental protocols. The power of
      theoretical modeling is demonstrated. 

PMID- 24328448
TI  - Advanced potential energy surfaces for condensed phase simulation.
AB  - Computational modeling at the atomistic and mesoscopic levels has undergone
      dramatic development in the past 10 years to meet the challenge of adequately
      accounting for the many-body nature of intermolecular interactions. At the heart
      of this challenge is the ability to identify the strengths and specific
      limitations of pairwise-additive interactions, to improve classical models to
      explicitly account for many-body effects, and consequently to enhance their
      ability to describe a wider range of reference data and build confidence in their
      predictive capacity. However, the corresponding computational cost of these
      advanced classical models increases significantly enough that statistical
      convergence of condensed phase observables becomes more difficult to achieve.
      Here we review a hierarchy of potential energy surface models used in molecular
      simulations for systems with many degrees of freedom that best meet the trade-off
      between accuracy and computational speed in order to define a sweet spot for a
      given scientific problem of interest. 

PMID- 24328449
TI  - Chemical synthesis of insulin analogs through a novel precursor.
AB  - Insulin remains a challenging synthetic target due in large part to its two
      chain, disulfide-constrained structure. Biomimetic single chain precursors
      inspired by proinsulin that utilize short peptides to join the A and B chains can
      dramatically enhance folding efficiency. Systematic chemical analysis of insulin
      precursors using an optimized synthetic protocol identified a 49 amino acid
      peptide named DesDi, which folds with high efficiency by virtue of an optimized
      structure and could be proteolytically converted to bioactive two-chain insulin.
      In subsequent applications, we observed that the folding of the DesDi precursor
      was highly tolerant to amino acid substitution at various insulin residues. The
      versatility of DesDi as a synthetic insulin precursor was demonstrated through
      the preparation of several alanine mutants (A10, A16, A18, B12, B15), as well as
      ValA16, an analog that was unattainable in prior reports. In vitro bioanalysis
      highlighted the importance of the native, hydrophobic residues at A16 and B15 as
      part of the core structure of the hormone and revealed the significance of the
      A18 residue to receptor selectivity. We propose that the DesDi precursor is a
      versatile synthetic intermediate for the preparation of diverse insulin analogs.
      It should enable a more comprehensive analysis of function to insulin structure
      than might not be otherwise possible through conventional approaches. 

PMID- 24328450
TI  - Synthesis, biosynthesis and biological activities of galbanic acid - A review.
AB  - Abstract Context: Galbanic acid (GA) is a biologically active sesquiterpene
      coumarin from Ferula species (Apiaceae). This compound showed various biological
      properties including anticancer, cancer chemopreventive, anticoagulant,
      antiviral, and antileishmanial activities. Objectives: This article is a review
      on the synthesis, biosynthesis, and biological activities of GA. In addition, we
      discussed gaps in our knowledge about GA that deserve future research. In this
      article, we also evaluated the drug-likeness of GA in silico. Methods: All
      relevant databases were searched for the terms "galbanic acid", "methyl
      galbanate", "Ferula" and "sesquiterpene coumarin" without limitation, up to May
      2013. Information on GA was collected via electronic search using Pubmed, Scopus,
      Web of Science, and Sciencedirect. All physicochemical parameters used for the
      prediction of drug-likeness were calculated using MarvinSketch (version 5.11,
      academic package, ChemAxon). Results: This compound showed various biological
      properties including anticancer, cancer chemopreventive, anticoagulant, antiviral
      and antileishmanial activities. GA can inhibit the growth of prostate cancer
      cells via decreasing androgen receptor abundance. In silico physicochemical
      studies on GA showed that this compound has drug-like properties, the parameters
      that are important to predict potential of a compound for being a future drug.
      Conclusion: GA is a valuable natural product with various biological activities.
      New discoveries with GA are to be expected.

PMID- 24328451
TI  - Silver-catalyzed radical tandem cyclization for the synthesis of 3,4
      disubstituted dihydroquinolin-2(1H)-ones.
AB  - A silver-catalyzed tandem decarboxylative radical addition/cyclization of N
      arylcinnamamides with aliphatic carboxylic acids is reported. This method affords
      a novel and straightforward route to various 3,4-disubstituted dihydroquinolin
      2(1H)-ones in aqueous solution. 

PMID- 24328452
TI  - A reappraisal of the deconditioning hypothesis in low back pain: review of
      evidence from a triumvirate of research methods on specific lumbar extensor
      deconditioning.
AB  - OBJECTIVE: 'Disuse' and 'Deconditioning' in relation to low back pain (LBP) are
      terms often used interchangeably. Discussions of 'disuse' refer to general
      physical inactivity, which evidence suggests does not differ between symptomatic
      and asymptomatic persons. 'Deconditioning' refers to a decrease in function,
      commonly both cardiovascular/aerobic fitness and muscular strength/endurance,
      again noting little difference. However, examination of decreased function
      relating specifically to lumbar extensor musculature deconditioning has yet to be
      examined, corroborating all possible methods. Thus, this review attempts to
      reappraise the deconditioning hypothesis in LBP, specifically considering lumbar
      extensor deconditioning. METHODS: A literature review was conducted examining
      both cross-sectional and prospective data on specific lumbar extensor
      deconditioning and LBP. A narrative approach and 'snowballing' style literature
      search was used involving initial use of PubMed and Google Scholar databases
      searching up to December 2012. Included were studies utilizing the following
      three research methods, allowing specific induction of the role of such
      deconditioning; (1) strength/endurance testing of the isolated lumbar extensor
      musculature, (2) imaging and histochemical examination of the lumbar extensor
      musculature, and (3) fatigue testing of the lumbar extensor musculature using
      electromyography. RESULTS/FINDINGS: Despite issues interpreting individual
      studies due to methods, the majority of evidence suggests LBP is associated with
      decreased strength/endurance, atrophy, and excessive fatigability of the lumbar
      extensors. Prospective studies also suggest lumbar extensor deconditioning may be
      a common risk factor predicting acute low back injury and LBP. CONCLUSIONS: The
      hypothesis of specific lumbar extensor deconditioning as being a causal factor in
      LBP is presently well supported. It is by no means the only causative factor and
      further research should more rigorously test this hypothesis addressing the
      methodological issues highlighted regarding previous studies. However, its role
      suggests specific exercise may be a worthwhile preventative and rehabilitative
      approach.

PMID- 24328454
TI  - Inactivation of E. coli O157:H7 in cultivable soil by fast and slow pyrolysis
      generated biochar.
AB  - An exploratory study was performed to determine the influence of fast pyrolysis
      (FP) and slow pyrolysis (SP) biochars on enterohemorrhagic Escherichia coli
      O157:H7 (EHEC) in soil. Soil + EHEC (inoculated at 7 log colony-forming units
      [CFU]/g of soil) + 1 of 12 types of biochar (10% total weight:weight in soil) was
      stored at 22 degrees C and sampled for 8 weeks. FP switchgrass and FP horse
      litter biochars inactivated 2.8 and 2.1 log CFU/g more EHEC than no-biochar soils
      by day 14. EHEC was undetectable by surface plating at weeks 4 and 5 in standard
      FP switchgrass, FP oak, and FP switchgrass pellet biochars. Conversely, EHEC
      populations in no-biochar control samples remained as high as 5.8 and 4.0 log
      CFU/g at weeks 4 and 5, respectively. Additionally, three more SP hardwood pellet
      biochars (generated at 500 degrees C for 1 h, or 2 h, or generated at 700 degrees
      C for 30 min) inactivated greater numbers of EHEC than did the no-biochar control
      samples during weeks 4 and 5. These results suggest that biochar can inactivate
      E. coli O157:H7 in cultivable soil, which might mitigate risks associated with
      EHEC contamination on fresh produce.

PMID- 24328453
TI  - Plasma polymer-coated contact lenses for the culture and transfer of corneal
      epithelial cells in the treatment of limbal stem cell deficiency.
AB  - Extensive damage to the limbal region of the cornea leads to a severe form of
      corneal blindness termed as limbal stem cell deficiency (LSCD). Whereas most
      cases of corneal opacity can be treated with full thickness corneal transplants,
      LSCD requires stem cell transplantation for successful ocular surface
      reconstruction. Current treatments for LSCD using limbal stem cell
      transplantation involve the use of murine NIH 3T3 cells and human amniotic
      membranes as culture substrates, which pose the threat of transmission of animal
      derived pathogens and donor tissue-derived cryptic infections. In this study, we
      aimed to produce surface modified therapeutic contact lenses for the culture and
      delivery of corneal epithelial cells for the treatment of LSCD. This approach
      avoids the possibility of suture-related complications and is completely
      synthetic. We used plasma polymerization to deposit acid functional groups onto
      the lenses at various concentrations. Each surface was tested for its suitability
      to promote corneal epithelial cell adhesion, proliferation, retention of stem
      cells, and differentiation and found that acid-based chemistries promoted better
      cell adhesion and proliferation. We also found that the lenses coated with a
      higher percentage of acid functional groups resulted in a higher number of cells
      transferred onto the corneal wound bed in rabbit models of LSCD.
      Immunohistochemistry of the recipient cornea confirmed the presence of
      autologous, transplanted 5-bromo-2'-deoxyuridine (BrdU)-labeled cells.
      Hematoxylin staining has also revealed the presence of a stratified epithelium at
      26 days post-transplantation. This study provides the first evidence for in vivo
      transfer and survival of cells transplanted from a contact lens to the wounded
      corneal surface. It also proposes the possibility of using plasma polymer-coated
      contact lenses with high acid functional groups as substrates for the culture and
      transfer of limbal cells in the treatment of LSCD. 

PMID- 24328455
TI  - High photocatalytic activity of transparent films composed of ZnO nanosheets.
AB  - Nanometric thin films were prepared by dip-coating and inkjet printing ZnO
      nanosheets on glass plates. The side-by-side alignment of the ZnO nanosheets on
      the substrate resulted in thin, transparent, oriented ZnO surfaces with the high
      energy {001} facets exposed. The method of nanosheet deposition affected the film
      morphology; the dip-coated films were very smooth and nonporous, while the inkjet
      printed films were rough and porous with the estimated void volume approximately
      60-70% of the total film volume. The first-order rate constants for the
      photocatalytic degradation of 4-chlorophenol on the nanosheet-based films were
      approximately 2 times larger than those on nanocolumnar ZnO films or ZnO films
      prepared by the sol-gel technique. We attribute the high photocatalytic activity
      of the ZnO nanosheets to the fact that their {001} facets were predominantly
      exposed to the oxidized substrate. This surface arrangement and the simplicity of
      fabricating the ZnO nanosheet-based films make them promising for the
      construction of optical devices and dye-sensitized solar cells. 

PMID- 24328456
TI  - Formation and ingression of division furrow can progress under the inhibitory
      condition of actin polymerization in ciliate Tetrahymena pyriformis.
AB  - In eukaryotic cells that multiply by binary fission, the interaction of actin
      filaments with myosin II in the contractile ring is widely recognized to generate
      force for membrane ingression into the cleavage furrow; however, the expression
      of myosin II is restricted in animals, yeast, fungi, and amoeba (collectively,
      unikonts). No corresponding motor protein capable of forming mini-filaments that
      could exert sufficient tension to cleave the cell body is found in bikonts,
      consisting of planta, algae, and most protozoa; however, cells in some bikont
      lineages multiply by binary fission, as do animal cells. Of these, the ciliate
      Tetrahymena is known to form an actin ring beneath the division furrow in
      cytokinesis. Here, we investigated the role of filamentous actin in the
      cytokinesis of Tetrahymena pyriformis by treating synchronized dividing cells
      with an actin-inhibiting drug, Latrunculin-A. Video microscopic observation of
      live cells undergoing cytokinesis was performed, and contrary to expectation, we
      found that initiation of furrow ingression and its progress are not suppressed
      under the inhibitory condition of actin polymerization in Tetrahymena cells. We
      suggest that an actin filament-independent mechanism of binary fission may have
      been acquired during the evolution in this organism. 

PMID- 24328457
TI  - Sexual dysfunction in multiple sclerosis: still a neglected problem?

PMID- 24328458
TI  - Accessibility of medical services for persons with disabilities: comparison with
      the general population in Korea.
AB  - PURPOSE: This study investigated the accessibility of medical services to people
      with disabilities (PWD) in Korea in comparison with the general population (GP)
      and examined factors influencing access to health care. METHODS: Data from the
      2011 Korean National Health and Nutrition Examination Survey and the 2011
      National Survey of Disabled People were used. Participants included PWD (n =
      5636) and the GP (n = 6646) aged 19 and above. RESULTS: Of the PWD group, 807
      (14.8%) reported difficulty in accessing medical services compared with 284
      (4.2%) of the GP group (p < 0.001). In the PWD group, the most frequently
      reported reasons for not receiving medical services when needed were lack of
      money (58.8%) and lack of transportation (18.6%). Problems accessing medical
      services were associated with sex, age, employment status, household income,
      health insurance type, chronic disease, and disability type and grade.
      CONCLUSIONS: PWD experienced more barriers in accessing medical services despite
      needing services more frequently than did those in the GP group. Compared to
      barriers faced by the GP, barriers for PWD were environmental rather than
      personal, which indicates the need for social policies to remove or reduce
      barriers and improve access to care. Implications for Rehabilitation Health Care
      Environment People with disabilities are likely to have difficulty in accessing
      medical services. Barriers are associated with environmental factors (e.g. lack
      of money or transportation), necessitating policies to reduce them.

PMID- 24328459
TI  - A novel spelling system for locked-in syndrome patients using only eye contact.
AB  - PURPOSE: We developed and evaluated a novel spelling system for patients with
      locked-in syndrome: patients with tetraplegia, not able to talk, and only able to
      blink their eyes. METHOD: A new communication grid was compared with existing non
      technical communication methods for practical daily use. The means of the number
      of decision steps to reach a full sentence were compared testing 10 sentences
      relevant in daily care. These 10 sentences together encompass all letters of the
      alphabet. RESULTS: The new communication grid is organised alphabetically in 4
      columns and 2 main rows, with each row subdivided in three rows. The first column
      contains vowels while the other columns contain consonants. Letters in each
      column are alphabetically ordered. When spelling a sentence the conversation
      partner counts the columns, until the patient indicates by an upward eye movement
      that the column contains the intended letter. Hereafter, the patient indicates by
      looking straight ahead or by looking down, whether the intended letter is in the
      upper or in the lower main row, respectively. The conversation partner will then
      read out the letters until the patient indicates the intended letter. Compared to
      other spelling systems, this system requires only vertical eye movement, is
      easier to memorise, and faster in use. The comparison of means of decision steps
      to reach the 10 full sentences for different communication grids shows that using
      the new communication grid is approximately one-third to three times faster than
      the existing spelling systems (p = 0.005). CONCLUSION: This new grid is a
      valuable communication tool, especially in situations, such as bathing, getting
      dressed or out of house activities where no devices are available. Implications
      for Rehabilitation Communication with patients with locked-in syndrome is a
      complicated and strenuous task. Communication methods, such as the alphabet board
      and brain-computer interfaces, are time consuming or too sophisticated to use in
      daily life tasks. This communication grid is fast, easy to use and memorise and
      requires only vertical eye movement.

PMID- 24328460
TI  - Association between IL-6-174G/C polymorphism and risk of multiple sclerosis: a
      meta-analysis.
AB  - OBJECTIVE: Interleukin-6 (IL-6) is a pleiotropic cytokine and important mediator
      of many inflammatory processes, which might affect susceptibility to multiple
      sclerosis (MS). The aim of this study was to assess the effect of IL-6-174G/C
      polymorphism on the risk of MS using a meta-analysis. MATERIALS AND METHODS: The
      Pubmed, ISI Web of Science, Wanfang, VIP, and China National Knowledge
      Infrastructure databases were screened and six studies were included in the meta
      analysis. Pooled odds ratios (ORs) with corresponding 95% confidence intervals
      (CI) were calculated to evaluate the association between the IL-6-174G/C
      polymorphism and risk of MS. RESULTS: No significant association between the IL-6
      174G/C polymorphism and risk of MS was observed in overall analyses. With
      stratification according to ethnicity, we found that carriers with the IL-6-174CC
      genotype had a 1.87-fold increased risk for the development of MS in Asians
      (recessive model: OR=1.87, 95% CI, 1.08-3.24), but not in Caucasians. CONCLUSION:
      This meta-analysis provides evidence that the IL-6-174G/C polymorphism may be a
      risk factor for the development of MS in Asians. Further association studies with
      a larger sample size are required to confirm the result in different populations.

PMID- 24328461
TI  - Double annulative cascade of tryptophan-containing peptides triggered by
      selectfluor.
AB  - A common dearomative strategy toward the kapakahines B/F and chaetominine natural
      products is reported. The proposed biomimetic strategy generates the tetracyclic
      alpha-carboline core in a single step, featuring a selectfluor-mediated
      dearomatization of preactivated N-Phth-Trp-Xaa-OR dipeptides at the C-terminus.
      The pivotal cascade includes a double annulation and the formation of three
      carbon-heteroatom bonds while gaining, for the first time, some insight on the
      diastereoselectivity outcome during the formation of the alpha-carboline
      fragment. 

PMID- 24328462
TI  - The contribution of systemic Escherichia coli infection to the early mortalities
      of commercial broiler chickens.
AB  - Avian pathogenic Escherichia coli (APEC) are a substantial burden to the global
      poultry industry. APEC cause a syndromic poultry infection known as
      colibacillosis, which has been previously associated with broiler chickens over 2
      weeks old. We recently reported that the intestinal tract of 1-day-old broilers
      harbours a rich reservoir of potentially pathogenic E. coli. Prior infections of
      the reproductive tract of breeders, egg hygiene and transportation all contribute
      to early colonization of the neonatal gut. Up to one-half of all flock deaths
      occur in the first week of production, but few data are available describing the
      contribution of E. coli. In the present study, all dead birds collected on the
      first daily welfare walk 48 and 72 h after chick placement underwent post-mortem
      examination. Diseased tissues were selectively cultured for E. coli and isolates
      subsequently virulotyped using 10 APEC virulence-associated genes (VAGs): astA,
      iss, irp2, iucD, papC, tsh, vat, cvi, sitA and ibeA. Approximately 70% of birds
      displayed signs of colibacillosis. Thirty distinct virulence profiles were
      identified among 157 E. coli. Isolates carried between zero and seven VAGs; ~ 30%
      of E. coli isolates carried five to seven VAGs, with 12.7% sharing the same VAG
      profile (astA, iss, irp2, iucD, tsh, cvi and sitA). Overall, this study
      demonstrates the significant contribution of E. coli infections to early broiler
      mortalities. The identification of a diverse E. coli population is unsurprising
      based on our previous findings. This work emphasizes the need for an effective
      vaccination programme and provides preliminary data for vaccine production.

PMID- 24328463
TI  - Pharmacogenetics and coumarin dosing--recalibrating expectations.

PMID- 24328464
TI  - A resitern's reflections on duty-hours reform.

PMID- 24328465
TI  - Getting through the night.

PMID- 24328466
TI  - Clinical practice. Cervical-cancer screening with human papillomavirus and
      cytologic cotesting.

PMID- 24328467
TI  - Images in clinical medicine. Myeloid sarcoma.

PMID- 24328468
TI  - Case records of the Massachusetts General Hospital. Case 38-2013. A 30-year-old
      man with fever and lymphadenopathy.

PMID- 24328469
TI  - Early specialty palliative care--translating data in oncology into practice.

PMID- 24328470
TI  - Macrophage accumulation in atherosclerosis.

PMID- 24328471
TI  - Colorectal-cancer incidence and mortality after screening.

PMID- 24328472
TI  - Colorectal-cancer incidence and mortality after screening.

PMID- 24328473
TI  - Colorectal-cancer incidence and mortality after screening.

PMID- 24328474
TI  - Intensive lifestyle intervention in type 2 diabetes.

PMID- 24328475
TI  - Intensive lifestyle intervention in type 2 diabetes.

PMID- 24328476
TI  - Intensive lifestyle intervention in type 2 diabetes.

PMID- 24328477
TI  - Intensive lifestyle intervention in type 2 diabetes.

PMID- 24328478
TI  - Intensive lifestyle intervention in type 2 diabetes.

PMID- 24328479
TI  - Intensive lifestyle intervention in type 2 diabetes.

PMID- 24328480
TI  - Carotid stenosis.

PMID- 24328481
TI  - Carotid stenosis.

PMID- 24328482
TI  - Carotid stenosis.

PMID- 24328483
TI  - Mild asthma.

PMID- 24328484
TI  - Mild asthma.

PMID- 24328485
TI  - Mild asthma.

PMID- 24328486
TI  - Aquagenic wrinkling of the palms in a patient with cystic fibrosis.

PMID- 24328487
TI  - Residency training--a decade of duty-hours regulations.

PMID- 24328488
TI  - Images in clinical medicine. Metastatic gas.

PMID- 24328489
TI  - Interactive medical case. An unusual case of abdominal pain.

PMID- 24328490
TI  - Surge in regulatory T cells does not prevent onset of hyperglycemia in NOD mice:
      immune profiles do not correlate with disease severity.
AB  - Immune profiling of non-obese diabetic (NOD) is a widely employed tool to assess
      the mechanisms of inflammatory insulitis. Our analysis of the female NOD colony
      revealed similar distribution of lymphoid lineages to wild type mice, and at
      various ages of prediabetic and diabetic mice. The profiles of mesenteric and
      pancreatic lymph nodes differ and often change reciprocally due to directed
      migration of T cells towards the site of inflammation. Significant events in our
      colony include early decline in CD4(+)CD25(+)CD62L(+) Treg, accompanied by
      gradual increase in CD4(+)CD25(+)FoxP3(+) Treg in peripheral lymphoid organs and
      pancreatic infiltrates. Impressively, aged euglycemic mice display significant
      transient rise in CD4(+)CD25(-)FoxP3(+) Treg in the thymus, pancreas and draining
      lymph nodes. A significant difference was superior viability of effector and
      suppressor cells from new onset diabetics in the presence of high interleukin-2
      (IL-2) concentrations in vitro as compared to cells of prediabetic mice. Overall,
      we found no correlation between FoxP3(+) Treg in the pancreatic lymph nodes and
      the inflammatory scores of individual NOD mice. CD25(-)FoxP3(+) Treg are markedly
      increased in the pancreatic infiltrates in late stages of inflammation, possibly
      an effort to counteract destructive insulitis. Considering extensive evidence
      that Treg in aged NOD mice are functionally sufficient, quantitative profiling
      evolves as an unreliable tool to assess mechanism and causes of inflammation
      under baseline conditions. Immune profiles are modulated by thymic output, cell
      migration, shedding of markers, proliferation, survival and in-situ evolution of
      regulatory cells.

PMID- 24328491
TI  - Characterization by deep sequencing of divergent plum bark necrosis stem pitting
      associated virus (PBNSPaV) isolates and development of a broad-spectrum PBNSPaV
      detection assay.
AB  - Plum bark necrosis stem pitting-associated virus (PBNSPaV), the causal agent of
      plum bark necrosis stem pitting disease, belongs to the genus Ampelovirus in the
      family Closteroviridae. The complete genome sequence of PBNSPaV isolates from
      four Prunus sources was determined by pyrosequencing. All isolates showed the
      same genomic organization as the PBNSPaV reference isolate. The least divergent
      isolate, found in a peach tree from China, showed an overall 91.8% of nucleotide
      identity with the type isolate. Two closely related isolates, defining a second
      cluster of diversity, were found in two Japanese plum lines from France and
      showed only 82.8% identity with the type isolate. On the other hand, they were
      highly homologous with two recently described PBNSPaV divergent isolates from
      China. The fourth and most divergent isolate, from a Chinese peach, showed only
      71.2% identity to other PBNSPaV isolates and was not detected by currently
      available PBNSPaV reverse-transcription polymerase chain reaction detection
      assays. Complete sequencing of the divergent isolates allowed the development of
      a more broad-spectrum detection test targeting a conserved region in the P61
      gene. Taken together, these results indicate a much broader diversity of PBNSPaV
      than previously thought and provide for a more robust detection of this still
      poorly characterized pathogen.

PMID- 24328493
TI  - Phylogeny of the genus Synchytrium and the development of TaqMan PCR assay for
      sensitive detection of Synchytrium endobioticum in soil.
AB  - Potato wart, caused by the fungal pathogen Synchytrium endobioticum, is a serious
      disease with the potential to cause significant economic damage. The small
      subunit (SSU) and internal transcribed spacer (ITS) ribosomal DNA (rDNA) were
      sequenced for several Synchytrium spp., showing a high rate of variability for
      both of these markers among the different species and monophyly of the genus
      within phylum Chytridiomycota. The intergenic nontranscribed spacer (IGS) of rDNA
      was sequenced for different pathotypes and showed no intraspecific variation
      within S. endobioticum, similar to the other rDNA markers from this study. To
      facilitate screening for the pathogen in soil, three TaqMan polymerase chain
      reaction (PCR) assays were developed from SSU, ITS, and IGS rDNA sequences to
      detect S. endobioticum sporangia in the chloroform-flotation fraction of sieved
      soil extracts. In the screening portion of the method, a first TaqMan assay
      targeting the SSU rDNA was developed with positive results that were further
      confirmed with amplicon melt analysis. A synthetic reaction control cloned into a
      plasmid was incorporated into the procedure, facilitating the validation of
      negative results. The presence of the reaction control did not adversely affect
      the efficiency of the SSU target amplification. A second TaqMan assay targeting
      the ITS-1 region was developed as a confirmatory test. There was 100% accordance
      between the SSU and ITS-1 TaqMan assays. Utilizing these two assays in tandem
      achieved good specificity for S. endobioticum, generating negative results with
      the cloned SSU and ITS-1 regions from all 14 other Synchytrium spp. considered.
      Spike recovery experiments indicated that these assays, targeting the SSU and ITS
      1 rDNA regions, developed from a phylogeny dataset of the genus, could reliably
      detect a single sporangium in the chloroform flotation fraction of a soil
      extract. Good correlation between microscopic detection of sporangia and PCR
      results in both positive and negative soil samples was dually demonstrated for
      both the SSU and ITS-1 assays.

PMID- 24328494
TI  - Induction of salicylic acid-mediated defense response in perennial ryegrass
      against infection by Magnaporthe oryzae.
AB  - Incorporation of plant defense activators is an innovative approach to
      development of an integrated strategy for the management of turfgrass diseases.
      The effects of salicylic acid (SA), benzothiadiazole (BTH, chemical analog of
      SA), jasmonic acid (JA), and ethephon (ET, an ethylene-releasing compound) on
      development of gray leaf spot in perennial ryegrass (Lolium perenne L.) caused by
      Magnaporthe oryzae were evaluated. Gray leaf spot disease incidence and severity
      were significantly decreased when plants were treated prior to inoculation with
      SA, BTH, and partially by ET but not by JA. Accumulation of endogenous SA and
      elevated expression of pathogenesis-related (PR)-1, PR-3.1, and PR-5 genes were
      associated with inoculation of plants by M. oryzae. Treatment of plants with SA
      enhanced expression levels of PR-3.1 and PR-5 but did not affect the PR-1 level,
      whereas BTH treatment enhanced relative expression levels of all three PR genes.
      Microscopic observations of leaves inoculated with M. oryzae revealed higher
      frequencies of callose deposition at the penetration sites in SA- and BTH-treated
      plants compared with the control plants (treated with water). These results
      suggest that early and higher induction of these genes by systemic resistance
      inducers may provide perennial ryegrass with a substantial advantage to defend
      against infection by M. oryzae.

PMID- 24328492
TI  - Complex molecular relationship between vegetative compatibility groups (VCGs) in
      Verticillium dahliae: VCGs do not always align with clonal lineages.
AB  - Verticillium wilts caused by the soilborne fungus Verticillium dahliae are among
      the most challenging diseases to control. Populations of this pathogen have been
      traditionally studied by means of vegetative compatibility groups (VCGs) under
      the assumption that VCGs comprise genetically related isolates that correlate
      with clonal lineages. We aimed to resolve the phylogenetic relationships among
      VCGs and their subgroups based on sequences of the intergenic spacer region (IGS)
      of the ribosomal DNA and six anonymous polymorphic sequences containing single
      nucleotide polymorphisms (VdSNPs). A collection of 68 V. dahliae isolates
      representing the main VCGs and subgroups (VCGs 1A, 1B, 2A, 2B, 3, 4A, 4B, and 6)
      from different geographic origins and hosts was analyzed using the seven DNA
      regions. Maximum parsimony (MP) phylogenies inferred from IGS and VdSNP sequences
      showed five and six distinct clades, respectively. Phylogenetic analyses of
      individual and combined data sets indicated that certain VCG subgroups (e.g.,
      VCGs 1A and 1B) are closely related and share a common ancestor; however, other
      subgroups (e.g., VCG 4B) are more closely related to members of a different VCG
      (e.g., VCG 2A) than to subgroups of the same VCG (VCG 4B). Furthermore, MP
      analyses indicated that VCG 2B is polyphyletic, with isolates placed in at least
      three distinct phylogenetic lineages based on IGS sequences and two lineages
      based on VdSNP sequences. Results from our study suggest the existence of main
      VCG lineages that contain VCGs 1A and 1B; VCGs 2A and 4B; and VCG 4A, for which
      both phylogenies agree; and the existence of other VCGs or VCG subgroups that
      seem to be genetically heterogeneous or show discrepancies in their phylogenetic
      placement: VCG 2B, VCG 3, and VCG 6. These results raise important caveats
      regarding the interpretation of VCG analyses: genetic homogeneity and close
      evolutionary relationship between members of a VCG should not be assumed.

PMID- 24328495
TI  - Folate intake and risk of bladder cancer: a meta-analysis of epidemiological
      studies.
AB  - Epidemiological studies have reported conflicting results between folate intake
      and bladder cancer risk. We conducted a meta-analysis of epidemiological studies
      published between 1996 and June 2013 on the relationship between folate intake
      and bladder cancer. We quantified associations with bladder cancer using meta
      analysis of risk estimates (REs) associated to the highest versus the lowest
      category of folate intake using random effect models. Seven cohort and six case
      control studies were eligible for inclusion. A significantly decreased risk with
      bladder cancer was observed in overall folate intake group (RE = 0.84; 95% CI,
      0.72-0.96) and subgroup of case-control studies (RE = 0.73; 95% CI, 0.57-0.89),
      but not in cohort studies (RE = 0.96; 95% CI, 0.81-1.10) when comparing the
      highest with the lowest category of folate intake. No heterogeneity and
      publication bias were observed across studies. Although the current evidence,
      mainly based on data from case-control studies, supports an inverse association
      between folate intake and bladder cancer, additional large and well-designed
      cohort studies are needed before definitive conclusions can be drawn.

PMID- 24328497
TI  - Multi-country health surveys: are the analyses misleading?
AB  - BACKGROUND: The aim of this paper was to review the types of approaches currently
      utilized in the analysis of multi-country survey data, specifically focusing on
      design and modeling issues with a focus on analyses of significant multi-country
      surveys published in 2010. METHODS: A systematic search strategy was used to
      identify the 10 multi-country surveys and the articles published from them in
      2010. The surveys were selected to reflect diverse topics and foci; and provide
      an insight into analytic approaches across research themes. The search identified
      159 articles appropriate for full text review and data extraction. RESULTS: The
      analyses adopted in the multi-country surveys can be broadly classified as:
      univariate/bivariate analyses, and multivariate/multivariable analyses.
      Multivariate/multivariable analyses may be further divided into design- and model
      based analyses. Of the 159 articles reviewed, 129 articles used model-based
      analysis, 30 articles used design-based analyses. Similar patterns could be seen
      in all the individual surveys. CONCLUSION: While there is general agreement among
      survey statisticians that complex surveys are most appropriately analyzed using
      design-based analyses, most researchers continued to use the more common model
      based approaches. Recent developments in design-based multi-level analysis may be
      one approach to include all the survey design characteristics. This is a
      relatively new area, however, and there remains statistical, as well as applied
      analytic research required. An important limitation of this study relates to the
      selection of the surveys used and the choice of year for the analysis, i.e., year
      2010 only. There is, however, no strong reason to believe that analytic
      strategies have changed radically in the past few years, and 2010 provides a
      credible snapshot of current practice.

PMID- 24328496
TI  - Cultural and linguistic adaptation of a multimedia colorectal cancer screening
      decision aid for Spanish-speaking Latinos.
AB  - As the United States becomes more linguistically and culturally diverse, there is
      a need for effective health communication interventions that target diverse,
      vulnerable populations, including Latinos. To address such disparities, health
      communication interventionists often face the challenge to adapt existing
      interventions from English into Spanish in a way that retains essential elements
      of the original intervention while also addressing the linguistic needs and
      cultural perspectives of the target population. The authors describe the
      conceptual framework, context, rationale, methods, and findings of a formative
      research process used in creating a Spanish-language version of an evidence-based
      (English language) multimedia colorectal cancer screening decision aid. The
      multistep process included identification of essential elements of the existing
      intervention, literature review, assessment of the regional context and
      engagement of key stakeholders, and solicitation of direct input from target
      population. The authors integrated these findings in the creation of the new
      adapted intervention. They describe how they used this process to identify and
      integrate sociocultural themes such as personalism (personalismo), familism
      (familismo), fear (miedo), embarrassment (verguenza), power distance (respeto),
      machismo, and trust (confianza) into the Spanish-language decision aid. 

PMID- 24328498
TI  - Molecular water oxidation mechanisms followed by transition metals: state of the
      art.
AB  - One clean alternative to fossil fuels would be to split water using sunlight.
      However, to achieve this goal, researchers still need to fully understand and
      control several key chemical reactions. One of them is the catalytic oxidation of
      water to molecular oxygen, which also occurs at the oxygen evolving center of
      photosystem II in green plants and algae. Despite its importance for biology and
      renewable energy, the mechanism of this reaction is not fully understood.
      Transition metal water oxidation catalysts in homogeneous media offer a superb
      platform for researchers to investigate and extract the crucial information to
      describe the different steps involved in this complex reaction accurately. The
      mechanistic information extracted at a molecular level allows researchers to
      understand both the factors that govern this reaction and the ones that derail
      the system to cause decomposition. As a result, rugged and efficient water
      oxidation catalysts with potential technological applications can be developed.
      In this Account, we discuss the current mechanistic understanding of the water
      oxidation reaction catalyzed by transition metals in the homogeneous phase, based
      on work developed in our laboratories and complemented by research from other
      groups. Rather than reviewing all of the catalysts described to date, we focus
      systematically on the several key elements and their rationale from molecules
      studied in homogeneous media. We organize these catalysts based on how the
      crucial oxygen-oxygen bond step takes place, whether via a water nucleophilic
      attack or via the interaction of two M-O units, rather than based on the
      nuclearity of the water oxidation catalysts. Furthermore we have used DFT
      methodology to characterize key intermediates and transition states. The
      combination of both theory and experiments has allowed us to get a complete view
      of the water oxidation cycle for the different catalysts studied. Finally, we
      also describe the various deactivation pathways for these catalysts. 

PMID- 24328499
TI  - Molecular characterization of Salmonella enterica serovar 4,[5],12:i:- DT193
      ASSuT strains from two outbreaks in Italy.
AB  - Salmonella enterica subsp. enterica serovar 4,[5],12:i:- DT193 is recognized as
      an emerging monophasic variant of Salmonella Typhimurium in many European
      countries. Resistance to ampicillin, streptomycin, sulphonamides, and
      tetracycline (R-type ASSuT) is described as one of the most common profiles of
      resistance within this clone. Recently, strains presenting such features were
      isolated from two unrelated outbreaks in Italy. Strains were characterized by
      pulsed-field gel electrophoresis (PFGE), performed with XbaI, BlnI, and SpeI, and
      multiple-locus variable-number tandem repeat analysis (MLVA). XbaI-PFGE showed
      strains related to the two outbreaks as indistinguishable. Conversely, both BlnI
      PFGE and MLVA characterized the strains related the two outbreaks as different.
      XbaI-PFGE identified two profiles, differing by one band, within strains isolated
      from one of the two outbreaks. Also BlnI-PFGE and MLVA generated different
      profiles among the strains related to that outbreak. Combining the PFGE profiles
      obtained by XbaI and BlnI and comparing them with the MLVA profiles, the two
      methods grouped the same isolates based on identity. Moreover, genomic deletions
      of the genes included in the operon fljAB, the flanking iroB gene, and the
      closely located STM2757 gene were investigated. For all strains, the same profile
      of deletion characterized by the absence of fljA, fljB, and hin genes and the
      presence of STM2757 and iroB genes was identified. This profile of deletion
      represents a mixture between two profiles of Salmonella 4,[5],12:i:- described as
      the "Spanish" and the "U.S." clones. This study demonstrated that although
      strains of Salmonella 4,[5],12:i:- DT193 ASSuT are highly clonal, minor
      differences between strains may be seen during the same outbreak by using in
      parallel PFGE with different restriction enzymes, MLVA, and the analysis of
      molecular markers related to the operon fljAB. The combination of these different
      molecular approaches was essential to clarify the epidemiological relationship
      among the strains.

PMID- 24328500
TI  - Polynucleotide phosphorylase is required for Escherichia coli O157:H7 growth
      above refrigerated temperature.
AB  - BACKGROUND: The growth of Escherichia coli O157:H7 in contaminated dairy and
      other refrigerated food products due to temperature fluctuation poses a major
      food safety threat. Effective control or inhibition of E. coli O157:H7 growth
      depends on our understanding of mechanisms that regulate its growth at low
      temperature. We hypothesized that polynucleotide phosphorylase (PNPase) plays a
      critical role in E. coli O157:H7 low-temperature growth. METHODS: To test this
      hypothesis, the pnp deletion mutant of E. coli O157:H7 was generated using the
      lambda Red recombinase system, and the growth and survival of wild-type and pnp
      deletion mutant strains were compared at low temperatures. RESULTS: The growth of
      pnp deletion mutant strains in Luria Broth (LB) and agar plate at 37 degrees C
      was similar to their corresponding wild-type strains, while the deletion of pnp
      impaired E. coli O157:H7 growth in LB at 10 degrees C and 22 degrees C; growth
      impairment could be partially recovered in the mutant strains by ectopic
      expression of the pnp complementation plasmid, demonstrating that growth
      impairment was PNPase-specific. During 14 days of 10 degrees C storage in both LB
      and milk, wild type strain EDL933 grew and reached >8 log10 colony-forming units
      per milliliter after 4 days of 10 degrees C storage, while EDL933Deltapnp
      gradually died off with effects more pronounced in milk, which were again
      mitigated by pnp overexpression. In addition, pnp deletion impaired the motility
      of E. coli O157:H7 but did not affect its susceptibility to H2O2. CONCLUSION:
      PNPase is required for the growth of E. coli O157:H7 at low temperature; PNPase
      thus provides a molecular target to control the growth of E. coli O157:H7, which
      may have important practical applications in dairy and other food industry.

PMID- 24328501
TI  - A modified molecular beacons-based multiplex real-time PCR assay for simultaneous
      detection of eight foodborne pathogens in a single reaction and its application.
AB  - Foodborne disease outbreaks are often caused by one of the major pathogens. Early
      identification of the causal pathogen is crucial for disease control and
      prevention. We describe a real-time polymerase chain reaction (rtPCR) assay that
      can identify, in a single reaction, up to eight common foodborne bacterial
      pathogens, including Salmonella enterica subsp. enterica, Listeria monocytogenes,
      Escherichia coli O157, Vibrio parahaemolyticus, V. vulnificus, Campylobacter
      jejuni, Enterobacter sakazakii, and Shigella spp. This multiplex rtPCR assay
      takes advantage of modified molecular beacons and the multicolor combinational
      probe coding strategy to discriminate each pathogen and the homo-tag assisted non
      dimer (HAND) system to prevent dimer formation. The detection limits of the assay
      ranged from 1.3*10(3) colony-forming units (CFU)/g stool (L. monocytogenes) to
      1.6*10(4) CFU/g stool (Shigella spp.). The target genes were 100% specific as
      assessed on 986 reference strains covering 41 species since no cross-reactions
      were observed. The assay was applied to the detection of foodborne pathogens in
      11,167 clinical samples and the results were compared with culture methods for
      further validation. The sensitivity and specificity of the rtPCR were 100% and
      99%, respectively. When performed in a 96-well rtPCR system, more than 90 samples
      could be analyzed within 3 h. Given the high accuracy, sensitivity, specificity,
      and short turn-around time, the established assay could be used for the rapid and
      reliable identification of the causative pathogens responsible for a certain
      foodborne disease outbreak and rapid screening of these major foodborne pathogens
      in laboratory-based surveillance of outpatient clinical samples or even food
      samples.

PMID- 24328502
TI  - Toll-like receptor agonists are potent inhibitors of human immunodeficiency virus
      type 1 replication in peripheral blood mononuclear cells.
AB  - Innate immune responses to microbial pathogens are initiated following the
      binding of ligand to specific pattern recognition receptors. Each pattern
      recognition receptor, which includes members of the Toll-like receptor (TLR)
      family, is specific for a particular type of pathogen associated molecular
      pattern ensuring that the organism can respond rapidly to a wide range of
      pathogens including bacteria, viruses, and fungi. We studied the extent to which
      agonists to endosomal TLR could induce anti-HIV-1 activity in peripheral blood
      mononuclear cells (PBMCs). When agonists to TLR3, TLR7, TLR8 and TLR9 were added
      prior to infection with HIV-1, they significantly reduced infection of peripheral
      blood mononuclear cells. Interestingly, agonists to TLR8 and TLR9 were highly
      effective at blocking HIV replication even when added as late as 48 h or 72 h,
      respectively, after HIV-1 infection, indicating that the anti-viral effect was
      durable and long lasting. Analysis of the induction of anti-viral genes after
      agonist activation of TLR indicated that all of the agonists induced expression
      of the type I interferons and interferon stimulated genes, although to variable
      levels that depended on the agonist used. Interestingly, only the agonist to
      TLR9, ODN2395 DNA, induced expression of type II interferon and the anti-HIV
      proteins Apobec3G and SAMHD1. By blocking TLR activity using an inhibitor to the
      MyD88 adaptor protein, we demonstrated that, at least for TLR8 and TLR9, the anti
      HIV activity was not entirely mediated by TLR activation, but likely by the
      activation of additional anti-viral sensors in HIV target cells. These findings
      suggest that agonists to the endosomal TLR function to induce expression of anti
      HIV molecules by both TLR-mediated and non-TLR-mediated mechanisms. Moreover, the
      non-TLR-mediated mechanisms induced by these agonists could potentially be
      exploited to block HIV-1 replication in recently HIV-exposed individuals.

PMID- 24328504
TI  - Modification of the adhesive properties of silicone-based coatings by block
      copolymers.
AB  - The improvement of the (bio)adhesive properties of elastomeric
      polydimethylsiloxane (PDMS) coatings is reported. This is achieved by a surface
      modification consisting of the incorporation of block copolymers containing a
      PDMS block and a poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) block in a
      PDMS matrix, followed by matrix cross-linking and immersion of the obtained
      materials in water. Contact angle measurements (CA), X-ray photoelectron
      spectroscopy (XPS), and atomic force microscopy (AFM) showed the presence of the
      PDMAEMA block at the surface, drastic morphology changes, and improved adhesion
      properties after immersion in water. Finally, underwater bioadhesion tests show
      that mussels adhere only to block copolymer-filled coatings and after immersion
      in water, i.e., when the PDMAEMA blocks have been brought to the coating surface.
      These observations highlight the significant role of hydrophilic groups in the
      surface modification of silicone coatings. 

PMID- 24328505
TI  - Implications of patients' socioeconomic status - what oncologists should be aware
      of.

PMID- 24328503
TI  - Fus1/Tusc2 is a novel regulator of mitochondrial calcium handling, Ca2+-coupled
      mitochondrial processes, and Ca2+-dependent NFAT and NF-kappaB pathways in CD4+ T
      cells.
AB  - AIMS: Fus1 has been established as mitochondrial tumor suppressor,
      immunomodulator, and antioxidant protein, but molecular mechanism of these
      activities remained to be identified. Based on putative calcium-binding and
      myristoyl-binding domains that we identified in Fus1, we explored our hypothesis
      that Fus1 regulates mitochondrial calcium handling and calcium-coupled processes.
      RESULTS: Fus1 loss resulted in reduced rate of mitochondrial calcium uptake in
      calcium-loaded epithelial cells, splenocytes, and activated CD4(+) T cells. The
      reduced rate of mitochondrial calcium uptake in Fus1-deficient cells correlated
      with cytosolic calcium increase and dysregulation of calcium-coupled
      mitochondrial parameters, such as reactive oxygen species production,
      DeltaMUH(+), mitochondrial permeability transition pore opening, and GSH content.
      Inhibition of calcium efflux via mitochondria, Na(+)/Ca(2+) exchanger
      significantly improved the mitochondrial calcium uptake in Fus1(-/-) cells. Ex
      vivo analysis of activated CD4(+) T cells showed Fus1-dependent changes in
      calcium-regulated processes, such as surface expression of CD4 and PD1/PD-L1,
      proliferation, and Th polarization. Fus1(-/-) T cells showed increased basal
      expression of calcium-dependent NF-kappaB and NFAT targets but were unable to
      fully activate these pathways after stimulation. INNOVATION: Our results
      establish Fus1 as one of the few identified regulators of mitochondrial calcium
      handling. Our data support the idea that alterations in mitochondrial calcium
      dynamics could lead to the disruption of metabolic coupling in mitochondria that,
      in turn, may result in multiple cellular and systemic abnormalities. CONCLUSION:
      Our findings suggest that Fus1 achieves its protective role in inflammation,
      autoimmunity, and cancer via the regulation of mitochondrial calcium and calcium
      coupled parameters.

PMID- 24328506
TI  - Scleraxis-overexpressed human embryonic stem cell-derived mesenchymal stem cells
      for tendon tissue engineering with knitted silk-collagen scaffold.
AB  - AIM: Despite our previous study that demonstrates that human embryonic stem cells
      (hESCs) can be used as seed cells for tendon tissue engineering after stepwise
      induction, suboptimal tendon regeneration implies that a new strategy needs to be
      developed for tendon repair. We investigated whether overexpression of the tendon
      specific transcription factor scleraxis (SCX) in hESC-derived mesenchymal stem
      cells (hESC-MSCs) together with knitted silk-collagen sponge scaffold could
      promote tendon regeneration. METHODS AND RESULTS: hESCs were initially
      differentiated into MSCs and then engineered with scleraxis (SCX+hESC-MSCs).
      Engineered tendons were constructed with SCX+hESC-MSCs and a knitted silk
      collagen sponge scaffold and then mechanical stress was applied. SCX elevated
      tendon gene expression in hESC-MSCs and concomitantly attenuated their adipogenic
      and chondrogenic potential. Mechanical stress further augmented the expression of
      tendon-specific genes in SCX+hESC-MSC-engineered tendon. Moreover, in vivo
      mechanical stimulation promoted the alignment of cells and increased the diameter
      of collagen fibers after ectopic transplantation. In the in vivo tendon repair
      model, the SCX+hESC-MSC-engineered tendon enhanced the regeneration process as
      shown by histological scores and superior mechanical performance compared with
      control cells, especially at early stages. CONCLUSION: Our study offers new
      evidence concerning the roles of SCX in tendon differentiation and regeneration.
      We demonstrated a novel strategy of combining hESCs, genetic engineering, and
      tissue-engineering principles for tendon regeneration, which are important for
      the future application of hESCs and silk scaffolds for tendon repair.

PMID- 24328507
TI  - Pediatric median arcuate ligament syndrome: surgical outcomes and quality of
      life.
AB  - BACKGROUND: The existence, etiology, diagnosis, and treatment of median arcuate
      ligament syndrome (MALS) have long been subjects of debate. To our knowledge,
      there have not been any studies assessing the effectiveness of surgical treatment
      in improving physical and psychological quality of life in pediatric patients.
      SUBJECTS AND METHODS: This is an Institutional Review Board-approved prospective
      study including all patients undergoing surgical treatment of MALS between 2009
      and 2012 at our institution. Demographic information, presenting symptoms,
      radiological imaging, procedure duration, hospital length of stay, and
      perioperative complications were gathered for analysis. Patients and their
      parents were asked to complete the Child Health Questionnaire, a physical and
      psychological health survey, both within 1 week prior to and at least 3 months
      following their surgery. RESULTS: Six patients underwent laparoscopic release for
      MALS. The majority of patients were female (n=5 [83.3%]), with an average age of
      15.7+/-1.5 years. Presenting symptoms lasted on average 16.5+/-12.7 months prior
      to treatment. Average pre- and postsurgical ultrasound celiac artery peak
      velocities with inspiration were 332.0+/-34.1 cm/second and 224.3+/-31.2
      cm/second, respectively, with a statistically significant decrease of 107.67
      cm/second (P=.03). The average follow-up period from time of surgery to time of
      quality of life survey completion was 13+/-11.3 months, with a range of 3-29
      months. A significant improvement from pre- to postsurgical scores was observed
      in the physical functioning (P=.03), mental health (P=.03), and self-esteem
      categories (P=.03) of the child assessment. Similarly, there was a significant
      postsurgical improvement in all categories pertaining to the parent's quality of
      life (P=.03). Improvement was also seen in the parents' perception of their
      child's physical functioning (P=.03), bodily pain/discomfort (P=.03), mental
      health (P=.03), and general health perceptions (P=.03). No intraoperative or
      postoperative complications occurred. CONCLUSIONS: Our preliminary results
      demonstrate that laparoscopic median arcuate ligament release for MALS in the
      pediatric population is safe and effective and improves overall quality of life
      for the patients and their parents. In carefully selected patients, laparoscopic
      release for MALS without additional celiac artery reconstruction normalizes blood
      flow in the celiac artery and improves physical and psychosocial quality of life
      for the child and his or her parents.

PMID- 24328508
TI  - Single-incision laparoscopic-assisted jejunostomy tube placement.
AB  - BACKGROUND: Feeding jejunostomy is an alternative enteral nutritional
      supplementation method for patients with functional gastrointestinal tracts. In
      this study, we introduced the novel, safe technique of single-incision
      laparoscopic-assisted jejunostomy (SIL-AJ) tube placement. SUBJECTS AND METHODS:
      We conducted a prospective record search and a retrospective review of all
      patients who received surgical jejunostomy tube placement in Chang Gung Memorial
      Hospital, Linkou, Taiwan, from October 2011 to December 2012. SIL-AJ, multiple
      incision laparoscopic jejunostomy (MIL-J), and open jejunostomy (O-J) were
      performed concurrently. We compared the demographic data, operative time,
      postoperative pain control, and postoperative complications among these groups.
      RESULTS: Forty patients who received surgical jejunostomy in this period were
      enrolled in the study. There were 14 patients with SIL-AJ, 10 with MIL-J, and 16
      with O-J. There were no differences in age, sex, American Society of
      Anesthesiologists status, body mass index, or malignancy distribution among the
      SIL-AJ, MIL-J, and O-J groups. The total operative times for the SIL-AJ, MIL-J,
      and O-J procedures were 53.3+/-11.5, 117.3+/-45.8, and 52.9+/-16.1 minutes,
      respectively; SIL-AJ and O-J had similar operative times, which were
      significantly shorter than the operative times in the MIL-J group (P<.001). The
      proportions of patients who began feeding within 24 hours in the SIL-AJ, MIL-J,
      and O-J groups were 100%, 70%, and 37%, respectively; the SIL-AJ group had a
      higher feeding rate at 24 hours than the two other groups (P=.001). The SIL-AJ
      and MIL-J groups had fewer postoperative complications than the O-J group
      (P=.011). CONCLUSIONS: SIL-AJ is a feasible and safe procedure that can be
      performed in patients who require alternative enteral feeding. Reduced
      postoperative pain, acceptable incisions, and quick feeding were observed in
      patients with SIL-AJ. Transumbilical SIL-AJ uses cost-effective appliances, and
      it is a relatively simple technique to learn and in which togain proficiency.

PMID- 24328509
TI  - Adrenal myelolipoma: operative indications and outcomes.
AB  - BACKGROUND: Adrenal myelolipoma (AM) is a benign lesion for which adrenalectomy
      is infrequently indicated. We investigated operative indications and outcomes for
      AM in a large single-institution series. SUBJECTS AND METHODS: A retrospective
      cohort study of prospectively collected data was conducted. Patients (>=16 years
      of age) who underwent adrenalectomy in the Division of General Surgery at Barnes
      Jewish Hospital (1993-2010) were grouped by operative indication (myelolipoma
      versus other pathology) and compared using nonparametric tests (alpha<0.05).
      RESULTS: Sixteen patients (4.0%) had myelolipomas resected out of 402 patients
      who underwent adrenalectomy. Fourteen patients with suspected AM underwent
      adrenalectomy, 13 (93%) of whom had AM confirmed on pathology. Indications for
      adrenalectomy were abdominal or flank pain, large tumor size (>8 cm), atypical
      radiologic appearance, and/or inferior vena cava compression. Three patients with
      suspected other adrenal lesions had AM confirmed on final pathology. Operative
      approach was laparoscopic in 15 cases and open in 1 case of a 21-cm lesion.
      Patients who underwent laparoscopic adrenalectomy for AM (n=15) or other adrenal
      pathology (n=343) were similar with respect to age, gender, American Society of
      Anesthesiologists classification, prior abdominal operation, tumor side,
      operative time, conversion rate, estimated blood loss, intraoperative
      complications, hospital length of stay, and 30-day morbidity. However, patients
      with resected AM had a higher body mass index (36.5+/-8.1 kg/m(2) versus 30.1+/
      7.5 kg/m(2); P<.01) and a larger preoperative tumor size (8.4+/-3.0 cm versus
      3.1+/-1.7 cm; P<.01). CONCLUSIONS: Laparoscopic adrenalectomy may be appropriate
      for patients with a presumptive diagnosis of AM and abdominal or flank pain,
      large tumor size, and/or uncertain diagnosis after imaging. Outcomes and
      morbidity following LA for AM and other adrenal pathology appear comparable.

PMID- 24328510
TI  - Monophasic and biphasic electrical stimulation induces a precardiac
      differentiation in progenitor cells isolated from human heart.
AB  - Electrical stimulation (ES) of cells has been shown to induce a variety of
      responses, such as cytoskeleton rearrangements, migration, proliferation, and
      differentiation. In this study, we have investigated whether monophasic and
      biphasic pulsed ES could exert any effect on the proliferation and
      differentiation of human cardiac progenitor cells (hCPCs) isolated from human
      heart fragments. Cells were cultured under continuous exposure to monophasic or
      biphasic ES with fixed cycles for 1 or 3 days. Results indicate that neither
      stimulation protocol affected cell viability, while the cell shape became more
      elongated and reoriented more perpendicular to the electric field direction.
      Moreover, the biphasic ES clearly induced the upregulation of early cardiac
      transcription factors, MEF2D, GATA-4, and Nkx2.5, as well as the de novo
      expression of the late cardiac sarcomeric proteins, troponin T, cardiac alpha
      actinin, and SERCA 2a. Both treatments increased the expression of connexin 43
      and its relocation to the cell membrane, but biphasic ES was faster and more
      effective. Finally, when hCPCs were exposed to both monophasic and biphasic ES,
      they expressed de novo the mRNA of the voltage-dependent calcium channel Cav
      3.1(alpha1G) subunit, which is peculiar of the developing heart. Taken together,
      these results show that ES alone is able to set the conditions for early
      differentiation of adult hCPCs toward a cardiac phenotype. 

PMID- 24328511
TI  - The glycemic/metabolic responses to meal tolerance tests at breakfast, lunch and
      dinner, and effects of the mitiglinide/voglibose fixed-dose combination on
      postprandial profiles in Japanese patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Meal tolerance tests (MTTs) are usually conducted at breakfast after
      overnight fasting in type 2 diabetes mellitus (T2DM) patients, but differences in
      postprandial glycemic responses between meals have been reported. OBJECTIVE: We
      conducted MTTs at breakfast, lunch, and dinner to examine the effects of a fixed
      combination of 10 mg mitiglinide/0.2 mg voglibose (the combination) on
      glycemic/metabolic responses to meals during the day in T2DM patients. MTTs with
      unified meals were conducted in 11 T2DM patients before and after 4 weeks of
      treatment with the combination administered thrice daily before meals.
      Glycemic/metabolic profiles measured before and at 30, 60, and 120 min after each
      meal were compared between each meal and between the baseline and treatment
      periods. RESULTS AND CONCLUSION: The combination significantly reduced
      postprandial hyperglycemia after each meal. Postprandial AUC0 - 120 min for
      insulin significantly decreased after lunch and dinner compared with after
      breakfast, while insulin levels significantly increased at only 30 min after
      breakfast and dinner. The combination also significantly increased postprandial C
      peptide and active glucagon-like peptide-1 levels, and reduced free fatty acid
      and triglyceride levels, but did not significantly affect glucagon levels
      compared with baseline, confirming that treatment with the combination improves
      postprandial responses in Japanese T2DM patients.

PMID- 24328512
TI  - Drug release from semisolid dosage forms: a comparison of two testing methods.
AB  - The aim of the present work was to extend our previous in-vitro drug release
      studies using semisolid dermatological bases with non-impregnated cellulose
      acetate membranes. A comparison of the performances of two apparatuses, the more
      commonly used Franz cell and the new modified USP (mini paddle with ointment
      holding cell) systems were applied to this work. Five different semisolid as well
      as two marketed preparations containing 1% diclofenac sodium were used. Complex,
      slightly non-linear release curves indicating sink conditions were found. This
      was explained by the co-diffusion of excipients modifying the characteristics of
      the membrane and the receiving medium dynamically. Although our test model is, as
      a rule, not suitable to establish an in-vivo-in-vitro correlation, good
      qualitative as well as quantitative correlations were found within some types of
      dermatological bases. The correlation between the results of the two in-vitro
      methods also depends on the type of semisolids studied. The release curve
      characteristics and the amount of diclofenac sodium released at 6 h were
      measured. Their repeatability and reproducibility were calculated. The slopes and
      Q-values were correlated with in-vivo data. In general, the modified USP method
      provided more precise results than the Franz cell method. 

PMID- 24328513
TI  - Into the breach: introduction to the 2012-2013 National Health Law Moot Court
      Competition problem.

PMID- 24328514
TI  - 2012-2013 National Health Law Moot Court Competition problem.

PMID- 24328515
TI  - 2012-2013 National Health Law Moot Court Competition: best brief.

PMID- 24328516
TI  - Medicaid versus the usufruct: a look at the conflicts between asset determination
      under Medicaid and Louisiana property law.

PMID- 24328517
TI  - Undocumented immigrants: lack of equal protection and its impact on public
      health.

PMID- 24328519
TI  - Helmet-to-helmet contact: avoiding a lifetime penalty by creating a duty to scan
      active NFL players for chronic traumatic encephalopathy.

PMID- 24328518
TI  - Changing the costs: a rational choice perspective on African Americans'
      healthcare consumption decisions.

PMID- 24328520
TI  - Disclosing the gray areas of mammography: should women with dense breast tissue
      remain in the dark about breast cancer screening alternatives?

PMID- 24328521
TI  - The paradox of nursing regulation: politics or patient safety?

PMID- 24328523
TI  - Multicomponent diversity-oriented synthesis of aza-lysine-peptide mimics.
AB  - Copper catalyzed coupling of Mannich reagents to aza-propargylglycine residues
      has been employed to synthesize constrained aza-lysine peptides. Employing growth
      hormone releasing peptide-6 (GHRP-6) as a model peptide and a variety of
      secondary amines, 18 aza-Lys analogs were synthesized by this so-called A(3)
      coupling reaction. This effective method for making constrained aza-Lys-peptides
      offers strong potential for exploring various recognition events implicating
      lysine residues including post-translational peptide modification. 

PMID- 24328524
TI  - Supported gold catalysis: from small molecule activation to green chemical
      synthesis.
AB  - With diminishing natural resources, there is an ever-increasing demand for cost
      effective and sustainable production of fine and commodity chemicals. For this
      purpose, there is a need for new catalytic methods that can permit efficient and
      targeted conversion of fossil and biorenewable feedstocks with lower energy
      requirements and environmental impact. A significant number of industrial
      catalytic processes are performed by platinum-group-metal (PGM)-based
      heterogeneous catalysts capable of activating a range of important small
      molecules, such as CO, O2, H2, and N2. In contrast, there is a general feeling
      that gold (Au) cannot act as an efficient catalyst because of its inability to
      activate most molecules, which is essential to any catalytic processes. As a
      consequence, researchers have long neglected the potential for use of gold as a
      catalyst. In recent years, however, chemists have put forth tremendous effort and
      progress in the use of supported gold catalysts to facilitate a variety of useful
      synthetic transformations. The seminal discovery by Haruta in 1987 that suitably
      prepared Au-based catalysts were surprisingly active for CO oxidation even at 200
      K initiated rapid development of the field. Since then, researchers have widely
      employed Au-based catalysts in many types of mild chemical processes, with
      special focus on selective reactions involving small molecules (for example, CO,
      H2O, O2, or H2) as a reactant. That gold in the form of tiny nanoparticles (NPs,
      generally less than 5 nm in diameter) can subtly activate the reactant molecules
      under mild conditions has been evoked to explain the superior effectiveness of
      gold compared with conventional PGMs. In this context, Au-based catalysts are
      gaining great significance in developing new green processes with improved
      selectivity and energy minimization. In this Account, we describe our efforts
      toward the development of a range of green and selective processes largely
      through the appropriate choice of Au catalysts coupled with the coactivation of a
      plethora of simple small molecules. We have focused on developing new mild and
      selective reductive transformations that can offer efficient alternatives to
      conventional Au-catalyzed hydrogenation processes. We have demonstrated Au
      catalyzed selective transformation involving HCOOH activation, Au-catalyzed
      selective reduction involving CO and H2O activation, and Au-catalyzed C-N/C-C
      bond formation via alcohol activation with high selectivity. The interplay
      between the support and gold plays a critical role in the success of these
      transformations, thus highlighting the crucial importance of support in tuning
      the performance of supported Au NPs. Most of the reactions can tolerate a range
      of functional groups, and some can occur under ambient conditions. Depending on
      the specific process, we propose several mechanistic scenarios that describe the
      plausible small-molecule-mediated reaction pathways. Additionally, we have
      observed an unusual reactant-promoted H2O or H2 activation over supported Au NPs,
      thus offering new strategies for green and facile synthesis of diverse amides and
      heteroaromatic nitrogen compounds. We anticipate that key insights into how
      simple small molecules are activated for further reaction over Au NPs should lead
      to a better understanding of gold catalysis and the development of new innovative
      PGM-free technologies. 

PMID- 24328525
TI  - The effects of emotional valence on hemispheric processing of metaphoric word
      pairs.
AB  - Recent theories of metaphor comprehension discuss the cognitive substrates
      involved in processing metaphors. However, the role of valence perception during
      metaphor comprehension has received little attention. The present study aims to
      examine the effect of emotional valence on metaphor processing, as well as the
      interaction between this effect and hemispheric differences. Metaphoric, literal,
      and meaningless word pairs were presented to 43 participants who performed a
      semantic judgment task. Results showed that processing of metaphors with negative
      valence was faster when done in the right hemisphere as compared with the left
      hemisphere. These findings indicate that emotional valence interacts with
      cognitive processes of metaphor comprehension. We discuss valence with respect to
      the class inclusion model and the fine versus coarse semantic coding model of
      metaphor processing. 

PMID- 24328527
TI  - Interleukin-16 gene polymorphisms rs4778889, rs4072111, rs11556218, and cancer
      risk in Asian populations: a meta-analysis.
AB  - OBJECTIVES: Some polymorphisms of the interleukin-16 (IL-16) gene are associated
      with various cancers. To resolve inconsistencies in published data, we performed
      a meta-analysis of studies of IL-16 polymorphisms and cancer risk. MATERIALS AND
      METHODS: Seven eligible studies pooling 1678 cases and 1937 controls were
      quantitatively analyzed to evaluate three IL-16 polymorphisms (rs4778889,
      rs4072111, rs11556218) and cancer risk. Hardy-Weinberg equilibrium (HWE) for
      controls was evaluated by goodness-of-fit chi-squared tests. Odds ratios (ORs)
      and their 95% confidence intervals (CIs) were calculated for each genetic model
      and allelic comparison. Data were pooled using fixed- or random-effects models
      depending on heterogeneity across studies. RESULTS: Our meta-analysis
      demonstrated that the IL-16 polymorphism rs11556218 was significantly associated
      with increased susceptibility to cancer in several models, including allelic
      contrast (OR=1.307; 95% CI, 1.108-1.541), heterozygote contrast (OR=1.650; 95%
      CI, 1.424-1.911), and dominant model (OR=1.605; 95% CI, 1.391-1.845). The result
      remained consistent after adjustment for age and gender. No significant
      association was found between IL-16 polymorphisms rs4778889 rs4072111 and cancer
      risk. CONCLUSIONS: The rs11556218 T/G polymorphism of the IL-16 gene was
      significantly associated with elevated cancer risk in Asian populations. Our
      results warrant larger, better-designed studies, including a greater ethnic
      variety.

PMID- 24328526
TI  - A functional polymorphism in MIR196A2 is associated with risk and progression of
      nasopharyngeal carcinoma in the Chinese population.
AB  - BACKGROUND: Genetic variations in microRNAs may alter their processing,
      expression, and binding to target mRNAs, consequently affecting many cancer
      related biological processes. Recently, a polymorphism rs11614913 in MIR196A2 was
      shown to affect the processing of the precursor microRNA into its mature forms
      and the repertoire of target mRNAs with which it interacts. We examined whether
      this polymorphism was relevant to the risk of occurrence or progression of
      nasopharyngeal carcinoma (NPC) in the Chinese population. METHODS: We genotyped
      the MIR196A2 rs11614913 in a case-control study of 1084 patients with NPC and
      1036 cancer-free controls using the TaqMan assay. The genetic associations with
      the risk of occurrence and progression of NPC were analyzed by logistic
      regression. RESULTS: We observed a significantly increased occurrence of NPC
      associated with the rs11614913 T allele (odds ratio [OR]=1.15, 95% confidence
      interval [CI]=1.02-1.32, p=0.026) compared with the C allele. The T allele was
      also significantly associated with the advanced local tumor invasion (T3+T4 vs.
      T1+T2; OR=1.27, 95% CI=1.04-1.54, p=0.015) and advanced lymph node metastasis
      (N2+N3 vs. N0+N1; OR=1.23, 95% CI=1.02-1.49, p=0.031) of NPC compared with the C
      allele. Furthermore, stratified analysis indicated that the increased
      susceptibility to advanced lymph node metastasis of NPC related to the T allele
      was more pronounced in patients with a positive family history (N2+N3 vs. N0+N1;
      p=0.016, test for homogeneity). CONCLUSIONS: Our study suggests that the
      functional polymorphism rs11614913 in the MIR196A2 gene may contribute to the
      risk of occurrence and progression of NPC in the Chinese population.

PMID- 24328528
TI  - ABCB1 C3435T polymorphism and the risk of coronary heart disease: a meta
      analysis.
AB  - BACKGROUND: ATP-binding cassette transporter 1 (ABCB1) plays a critical role in
      the development and progression of cardiovascular disease. Emerging evidence
      suggests that common functional polymorphisms in the ABCB1 gene might have an
      impact on an individual's susceptibility to coronary heart disease (CHD), but
      individually published results are inconclusive. This meta-analysis aimed to
      derive a more precise estimation of the relationship between ABCB1 C3435T
      polymorphism and CHD risk. METHOD: An extensive literary search for relevant
      studies was conducted in PubMed, Embase, Web of Science, Cochrane Library,
      CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National
      Knowledge Infrastructure (CNKI) databases from their inception through August
      1st, 2013. Meta-analysis was performed using the STATA 12.0 software. The crude
      odds ratio (OR) with 95% confidence interval (CI) were calculated. RESULTS: Seven
      clinical studies were included with a total of 13,074 CHD patients, including 378
      variant angina pectoris (VAP) patients, 2290 myocardial infarction (MI) patients,
      and 10,406 acute coronary syndrome (ACS) patients. Our meta-analysis results
      indicated that ABCB1 C3435T polymorphism may be associated with an increased risk
      of CHD, especially for MI and ACS among Caucasian populations. However, no
      statistically significant association was found between ABCB1 C3435T polymorphism
      and VAP risk, especially among Asian populations. Meta-regression analyses showed
      that clinical subtype and ethnicity may be the main sources of heterogeneity. No
      publication bias was detected in this meta-analysis. CONCLUSION: The current meta
      analysis suggests that ABCB1 C3435T polymorphism may contribute to the risk of
      CHD, especially for MI and ACS, among Caucasian populations. Thus, detection of
      ABCB1 C3435T polymorphism may be a promising biomarker for the early detection of
      CHD.

PMID- 24328529
TI  - Three silver linings in the cloud of old age: an autobiographical perspective.
AB  - Through the author's experiences as a gerontological social worker, graduate
      student in gerontology, and gerontology professor, the author discovered not only
      the cloud of old age, but three silver linings. 

PMID- 24328530
TI  - A high frequency of peripheral blood NKG2D+NK and NKT cells in euthyroid patients
      with new onset hashimoto's thyroiditis--a pilot study.
AB  - Hashimoto's thyroiditis (HT) is a T cell-mediated autoimmune disease. However,
      little is known about the role of different subsets of natural killer (NK) and
      natural killer T (NKT) cells at the early stage of the HT process. A total of 45
      euthyroid patients with new onset HT and 40 age/gender-matched healthy controls
      (HC) were examined for the frequency of different subsets of NK and NKT cells and
      their function by flow cytometry. In comparison with that in HC, significantly
      higher percentages of peripheral blood CD3-CD56+ NK, NKG2D+, NKp30+ NK and NKT
      cells, but significantly lower percentages of NKG2A+, KIR2DL3+ inhibitory NK and
      NKT cells were detected in the HT patients. Furthermore, the percentages of
      NKG2D+ NK cells were correlated positively with the concentrations of serum anti
      thyroid peroxidase antibody (TPOAb) in the HT patients. Moreover, the percentages
      of inducible IFN-gamma and CD107a+ NK cells in the HT patients were significantly
      higher than those in HC. Our data suggest that activated NK cells may participate
      in the early pathogenic process of HT. 

PMID- 24328531
TI  - Adsorption energies of poly(ethylene oxide)-based surfactants and nanoparticles
      on an air-water surface.
AB  - The self-assembly of polymer-based surfactants and nanoparticles on fluid-fluid
      interfaces is central to many applications, including dispersion stabilization,
      creation of novel 2D materials, and surface patterning. Very often these
      processes involve compressing interfacial monolayers of particles or polymers to
      obtain a desired material microstructure. At high surface pressures, however,
      even highly interfacially active objects can desorb from the interface. Methods
      of directly measuring the energy which keeps the polymer or particles bound to
      the interface (adsorption/desorption energies) are therefore of high interest for
      these processes. Moreover, though a geometric description linking adsorption
      energy and wetting properties through the definition of a contact angle can be
      established for rigid nano- or microparticles, such a description breaks down for
      deformable or aggregating objects. Here, we demonstrate a technique to quantify
      desorption energies directly, by comparing surface pressure-density compression
      measurements using a Wilhelmy plate and a custom-microfabricated deflection
      tensiometer. We focus on poly(ethylene oxide)-based polymers and nanoparticles.
      For PEO-based homo- and copolymers, the adsorption energy of PEO chains scales
      linearly with molecular weight and can be tuned by changing the subphase
      composition. Moreover, the desorption surface pressure of PEO-stabilized
      nanoparticles corresponds to the saturation surface pressure for spontaneously
      adsorbed monolayers, yielding trapping energies of ~10(3) k(B)T.

PMID- 24328532
TI  - Extracellular superoxide dismutase induces mouse embryonic fibroblast
      proliferative burst, growth arrest, immortalization, and consequent in vivo
      tumorigenesis.
AB  - AIMS: Rat sarcoma virus (RAS)-induced tumorigenesis has been suggested to follow
      a three-stage model consisting of an initial RAS activation, senescence
      induction, and evasion of p53-dependent senescence checkpoints. While reactive
      oxygen species act as second messengers in RAS-induced senescence, they are also
      involved in oncogenic transformation by inducing proliferation and promoting
      mutations. In the current work, we investigated the role of extracellular
      superoxide dismutase (SOD3) in RAS-induced senescence and immortalization in
      vitro and in vivo. We used a mouse embryonic fibroblast (MEF) primary cell model
      along with immortalized and transformed human cell lines derived from papillary
      and anaplastic thyroid cancer. RESULTS: Based on our data, sod3 RNA interference
      in H-RasV12-transduced cells markedly inhibited cell growth, while sod3 over
      expression in MEFs initially caused a proliferative burst followed by the
      activation of DNA damage checkpoints, induction of p53-p21 signal transduction,
      and senescence. Subsequently, sod3-transduced MEF cells developed co-operative
      p21-p16 down-regulation and acquired transformed cell characteristics such as
      increased telomerase activity, loss of contact inhibition, growth in low-nutrient
      conditions, and in vivo tumorigenesis. Interestingly, as previously reported with
      RAS, we showed a dose-dependent response to SOD3 in vitro and in vivo involving
      transcriptional and non-transcriptional regulatory mechanisms. INNOVATION: SOD3
      may mediate H-RasV12-induced initiation of primary cell immortalization.
      CONCLUSIONS: Our results indicate that SOD3 influences growth signaling in
      primary and cancer cells downstream of the ras oncogene and could serve as a
      therapy target at an early tumorigenesis phase.

PMID- 24328533
TI  - Catalytic conjugate addition of acyl anion equivalents promoted by
      fluorodesilylation.
AB  - The conjugate addition of acyl anion equivalents derived from 2-silyl-1,3
      dithianes to alpha,beta-unsaturated ketones and esters has been achieved using a
      substoichiometric amount of TBAF. High yields and short reaction times are
      observed for the addition of aryl-1,3-dithianes to a variety of cyclic and
      acyclic alpha,beta-unsaturated carbonyl acceptors. Observation of the reactive
      anion by (13)C NMR spectroscopy and extension to an asymmetric variant is also
      presented. 

PMID- 24328534
TI  - Up-regulation of inducible heat shock protein-70 expression in multiple sclerosis
      patients.
AB  - Inducible heat shock protein (HSP)70 (HSP70-1A and HSP70-1B proteins) is a
      chaperone responsible for assisting proper protein folding. Following stress
      conditions, HSP70 is highly up-regulated to mediate cytoprotective functions. In
      addition, HSP70 is able to trigger innate and adaptive immune responses that
      promote the immune recognition of antigens and to act as a cytokine when it is
      released. The data in the literature are controversial with regard to expression
      studies in peripheral blood mononuclear cells (PBMCs). In the present study, we
      aimed to examine if alterations of HSP70-1A/B expression are involved in the
      autoimmune pathogenesis of multiple sclerosis (MS). We determined both mRNA and
      protein expression in PBMCs of MS patients and healthy donors (HDs). We found a
      baseline increased expression of the HSPA1A gene in PBMCs from MS patients
      compared with HDs. Gene expression findings were associated with an increased
      protein expression of HSP70-1A/B in T lymphocytes (CD4+ and CD8+) and monocytes
      from MS patients under basal conditions that may reflect the immunological
      activation occurring in MS patients. We also provided evidence that heat shock
      (HS) stimulus induced HSP70-1A/B protein expression in HDs and MS patients, and
      that HS-induced HSP70-1A/B protein expression in monocytes correlated with the
      number of T2 lesions at baseline in MS patients. However, after
      lipopolysaccharide inflammatory stimulus, monocytes from MS patients failed to
      induce HSP70-1A/B protein expression. Our data hint at altered immune responses
      in MS and may indicate either a state of chronic stress or increased
      vulnerability to physiological immune responses in MS patients.

PMID- 24328536
TI  - Compliance and toxicity of the hypoxic radiosensitizer nimorazole in the
      treatment of patients with head and neck squamous cell carcinoma (HNSCC).
AB  - PURPOSE: To evaluate the compliance and toxicity of the hypoxic radiosensitizer
      nimorazole in head and neck cancer patients. METHODS: A retrospective study of
      patients with head and neck squamous cell carcinoma (HNSCC), treated in Denmark
      between 1990 and 2013. All patients treated with radical radiotherapy (+/-
      chemotherapy) [66-70 Gy; 33-35 fractions; 2 Gy/fraction; 5-6 fractions/week]
      concomitant with the hypoxic radiosensitizer nimorazole. Nimorazole was
      administered as oral tablets in doses of approximately 1.2 g/m(2) body surface
      area in connection with the first of each daily radiation treatment. A second
      daily dose of 1 g was given in connection with the second radiotherapy fraction
      in the accelerated fractionation regimen. The compliance was estimated as the
      percentage of the initially prescribed dose, which was received by each patient.
      The main side effects were recorded. RESULTS: A total of 1049 patients were
      investigated. The tolerance to nimorazole was fair: 58% of patients received the
      full prescribed total dose. Nausea and vomiting were the major complaints: among
      the 260 patients with dose reductions due to known side effects, (87%) were due
      to nausea/vomiting. All side effects ceased when treatment was interrupted, and
      neither severe nor long lasting side effects were observed. Female patients were
      significantly more likely to have dose reduction (OR 2.02; 95% CI 1.50-2.70), and
      nausea/vomiting. Patients aged more than 70 years were significantly more likely
      to have dose reduction. Patients who received less than 1100 mg/m(2) were
      significantly less likely to have dose reduction (OR 0.58; CI 0.44-0.78), and
      nausea/vomiting, compared to those who received 1100-1300 mg/m(2). The tolerance
      was also less in the group of patients received accelerated chemoradiotherapy (OR
      1.70; CI 1.20-2.50) with more association with nausea/vomiting (OR 2.09; CI 1.40
      3.10). CONCLUSION: The compliance to nimorazole is fair, with tolerable acute,
      but neither persistent nor late, toxicity. It can be administered with
      chemotherapy and different radiotherapy fractionation schedules.

PMID- 24328535
TI  - Detection of drug resistance-associated mutations in human immunodeficiency virus
      type 1 integrase derived from drug-naive individuals in Surabaya, Indonesia.
AB  - Although human immunodeficiency virus type 1 (HIV-1) infection causes serious
      health problems in Indonesia, information in regard to drug resistance is
      limited. We performed a genotypic study on HIV-1 integrase derived from drug
      naive individuals in Surabaya, Indonesia. Sequencing analysis revealed that no
      primary mutations associated with drug resistance to integrase inhibitors were
      detected; however, secondary mutations, V72I, L74I/M, V165I, V201I, I203M, and
      S230N, were detected in more than 5% of samples. In addition, V201I was conserved
      among all samples. Most integrase genes were classified into CRF01_AE genes.
      Interestingly, 40% of the CRF01_AE genes had an unusual insertion in the C
      terminus of integrase. These mutations and insertions were considered natural
      polymorphisms since these mutations coincided with previous reports, and
      integrase inhibitors have not been used in Indonesia. Our results indicated that
      further studies may be required to assess the impact of these mutations on
      integrase inhibitors prior to their introduction into Indonesia.

PMID- 24328537
TI  - Bioengineering of physiologically functional intrinsically innervated human
      internal anal sphincter constructs.
AB  - Muscle replacement for patients suffering from extensive tissue loss or
      dysfunction is a major objective of regenerative medicine. To achieve functional
      status, bioengineered muscle replacement constructs require innervation. Here we
      describe a method to bioengineer functionally innervated gut smooth muscle
      constructs using neuronal progenitor cells and smooth muscle cells isolated and
      cultured from intestinal tissues of adult human donors. These constructs
      expressed markers for contractile smooth muscle, glial cells, and mature neuronal
      populations. The constructs responded appropriately to physiologically relevant
      neurotransmitters, and neural network integration was demonstrated by responses
      to electrical field stimulation. The ability of enteric neuroprogenitor cells to
      differentiate into neuronal populations provides enormous potential for
      functional innervation of a variety of bioengineered muscle constructs in
      addition to gut. Functionally innervated muscle constructs offer a regenerative
      medicine-based therapeutic approach for neuromuscular replacement after trauma or
      degenerative disorders. 

PMID- 24328538
TI  - A correlation between the fate and non-extractable residue formation of 14C
      metalaxyl and enzymatic activities in soil.
AB  - Extracellular, oxidative soil enzymes like monophenol oxidases and peroxidases
      play an important role in transformation of xenobiotics and the formation of
      organic matter in soil. Additionally, these enzymes may be involved in the
      formation of non-extractable residues (NERs) of xenobiotics during humification
      processes. To examine this correlation, the fate of the fungicide (14)C metalaxyl
      in soil samples from Ultuna (Sweden) was studied. Using different soil
      sterilization techniques, it was possible to differentiate between free,
      immobilized, and abiotic ("pseudoenzyme"-like) oxidative activities. A
      correlation between the formation of metalaxyl NER and soil organic matter
      content, biotic activities, as well as extracellular phenoloxidase and peroxidase
      activities in the bulk soil and its particle size fractions was determined.
      Extracellular soil-bound enzymes were involved in NER formation (up to 8% of
      applied radioactivity after 92 days) of the fungicide independently from the
      presence of living microbes and different distributions of the NER in the soil
      humic subfractions.

PMID- 24328539
TI  - Biodegradation of triazine herbicide metribuzin by the strain Bacillus sp. N1.
AB  - By enrichment culturing of soil contaminated with metribuzin, a highly efficient
      metribuzin degrading bacterium, Bacillus sp. N1, was isolated. This strain grows
      using metribuzin at 5.0% (v/v) as the sole nitrogen source in a liquid medium.
      Optimal metribuzin degradation occurred at a temperature of 30oC and at pH 7.0.
      With an initial concentration of 20 mg L(-1), the degradation rate was 73.5% in
      120 h. If the initial concentrations were higher than 50 mg L(-1), the
      biodegradation rates decreased as the metribuzin concentrations increased. When
      the concentration was 100 mg L(-1), the degradation rate was only 45%.
      Degradation followed the pesticide degradation kinetic equation at initial
      concentrations between 5 mg L(-1) and 50 mg L(-1). When the metribuzin
      contaminated soil was mixed with strain N1 (with the concentration of metribuzin
      being 20 mg L(-1) and the inoculation rate of 10(11) g(-1) dry soil), the
      degradation rate of the metribuzin was 66.4% in 30 days, while the degradation
      rate of metribuzin was only 19.4% in the control soil without the strain N1.
      These results indicate that the strain N1 can significantly increase the
      degradation rate of metribuzin in contaminated soil.

PMID- 24328540
TI  - DDT and DDE concentrations in the blood of Mexican children residing in the
      southeastern region of Mexico.
AB  - The aim of this study was to assess the levels of dichlorodiphenyltrichloroethane
      (DDT) and dichlorodiphenyldichloroethylene (DDE) in the blood of children living
      in the southeastern region of Mexico. In this study, we found high levels of DDT
      and its principal metabolite (DDE) in the blood of children residing in the
      communities studied. The levels of total DDT found in our study ranged from
      4,676.4 ng/g lipid to 64,245.2 ng/g lipid. All of the children in the study had
      detectable levels of DDT and/or DDE. In conclusion, our data indicate that
      children living within the study areas are exposed to high levels of DDT and DDE.
      Moreover, these results can be used as a trigger to revisit local policies on
      environmental exposures.

PMID- 24328541
TI  - Effects of ozone fumigation treatment on the removal of residual difenoconazole
      from strawberries and on their quality.
AB  - The effect of ozone fumigation on the reduction of difenoconazole residue on
      strawberries was studied. Strawberries were immersed in 1.0 L of aqueous solution
      containing 400 MUL of the commercial product (250 g L(-1) of difenoconazole) for
      1 min. Then, they were dried and exposed to ozone gas (O3) at concentrations of
      0.3, 0.6 and 0.8 mg L(-1) for 1 h. The ozone fumigation treatments reduced the
      difenoconazole residue on strawberries to concentrations below 0.5 mg kg(-1),
      which corresponds to a 95% reduction. The strawberries treated with ozone and the
      control group, which was not treated with ozone, were stored at 4 degrees C for
      10 days. Some characteristics of the fruit were monitored throughout this period.
      Among these, pH, weight loss and total color difference did not change
      significantly (P > 0.05). The fumigation with ozone significantly affected the
      soluble solids, titratable acidity and ascorbic acid content (vitamin C) of the
      strawberries preventing a sharp reduction of these parameters during storage.

PMID- 24328543
TI  - Preparation of artificial antigen and egg yolk-derived immunoglobulin (IgY) of
      florfenicol amine for ELISA assay.
AB  - To investigate the feasibility of IgY technology for the immune detection of
      haptens, a specific egg yolk antibody (IgY) has been developed in order to detect
      the florfenicol amine (FFA) residues. FFA was conjugated to bovine serum albumin
      (BSA) by glutaraldehyde (GA) and the conjugate was used to immunize laying
      chickens. Anti-FFA IgY antibody was purified by PEG-6000 precipitation and
      identified by SDS-PAGE. The titer of anti-FFA IgY antibody reached a peak of
      1:128,000 after three booster injections. Checkerboard titration showed that a
      1:800 dilution of anti-FFA IgY could give an optical density (OD) at around 1.0
      at 10 MUg/mL FFA-OVA coating concentration. An indirect competitive enzyme-linked
      immunosorbent assay (icELISA) using specific anti-FFA IgY showed that the IC50
      value of anti-FFA IgY was 12.30 ng/mL and the regression curve equation was y = 
      13.71x + 64.95 (R (2) = 0.945). The strategy of developing anti-hapten IgY
      antibody is that it may be further used as a new reagent for an immunoassay of
      hapten residues.

PMID- 24328542
TI  - A sensitive LC-MS/MS method for measurement of organophosphorus pesticides and
      their oxygen analogs in air sampling matrices.
AB  - A rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been
      developed for determination of levels of the organophosphorus (OP) pesticides
      chlorpyrifos (CPF), azinphos methyl (AZM), and their oxygen analogs chlorpyrifos
      oxon (CPF-O) and azinphos methyl-oxon (AZM-O) on common active air sampling
      matrices. XAD-2 resin and polyurethane foam (PUF) matrices were extracted with
      acetonitrile containing stable-isotope labeled internal standards (ISTD).
      Analysis was accomplished in Multiple Reaction Monitoring (MRM) mode, and
      analytes in unknown samples were identified by retention time (+/-0.1 min) and
      qualifier ratio (+/-30% absolute) as compared to the mean of calibrants. For all
      compounds, calibration linearity correlation coefficients were >=0.996. Limits of
      detection (LOD) ranged from 0.15-1.1 ng/sample for CPF, CPF-O, AZM, and AZM-O on
      active sampling matrices. Spiked fortification recoveries were 78-113% from XAD-2
      active air sampling tubes and 71-108% from PUF active air sampling tubes. Storage
      stability tests also yielded recoveries ranging from 74-94% after time periods
      ranging from 2-10 months. The results demonstrate that LC-MS/MS is a sensitive
      method for determining these compounds from two different matrices at the low
      concentrations that can result from spray drift and long range transport in non
      target areas following agricultural applications. In an inter-laboratory
      comparison, the limit of quantification (LOQ) for LC-MS/MS was 100 times lower
      than a typical gas chromatography-mass spectrometry (GC-MS) method.

PMID- 24328544
TI  - Residues and enantiomeric profiling of organochlorine pesticides in sediments
      from Xinghua Bay, southern East China Sea.
AB  - The spatial distribution and chiral signatures of organochlorine pesticides
      (OCPs) in the surface sediments of Xinghua Bay, southern East China Sea, were
      investigated. The total OCP concentrations ranged from 9.15 to 40.5 ng/g dry
      weight, with a predominance of hexachlorocyclohexanes (HCHs) and
      dichlorodiphenyltrichloroethanes (DDTs). The isomer ratios of alpha-HCH/gamma-HCH
      (less than 1.0) and the predominant beta-HCH implied that HCH residues were
      derived not only from historical technical HCH use but also from the additional
      use of lindane in this area. The isomer ratios of p,p'-DDT/(p,p'-DDD + p,p'-DDE)
      and o,p'-DDT/p,p''-DDT, and a strong correlation (R = 0.83, P < 0.001) between
      p,p'-DDE and o,p'-DDT depicted a cocktail input pattern of dicofol-type DDT and
      technical DDT. Moreover, the fact that only cis-chlordane was detectable for all
      sampling stations suggested the past application of technical chlordane. Based on
      the sediment quality guidelines (SQG), gamma-HCH is the main OCP species of
      ecotoxicological concern in Xinghua Bay. Enantiomeric analysis showed that the
      (+)-enantiomers of alpha-HCH and o,p'-DDT were more prevalent than the (-)
      enantiomers in most samples, whereas both racemic and nonracemic residues existed
      for o,p'-DDD. These results implied that the SQG of chiral OCPs should be
      reassessed using concentrations of their individual enantiomers.

PMID- 24328545
TI  - Quantitative risk analysis for potentially resistant E. coli in surface waters
      caused by antibiotic use in agricultural systems.
AB  - Antibiotics are frequently used in agricultural systems to promote livestock
      health and to control bacterial contaminants. Given the upsurge of the resistant
      fecal indicator bacteria (FIB) in the surface waters, a novel statistical method
      namely, microbial risk assessment (MRA) was performed, to evaluate the
      probability of infection by resistant FIB on populations exposed to recreational
      waters. Diarrheagenic Escherichia coli, except E. coli O157:H7, were selected for
      their prevalence in aquatic ecosystem. A comparative study between a typical E.
      coli pathway and a case scenario aggravated by antibiotic use has been performed
      via Crystal Ball(r) software in an effort to analyze a set of available inputs
      provided by the US institutions including E. coli concentrations in US Great
      Lakes through using random sampling and probability distributions. Results from
      forecasting a possible worst-case scenario dose-response, accounted for an
      approximate 50% chance for 20% of the exposed human populations to be infected by
      recreational water in the U.S. However, in a typical scenario, there is a 50%
      chance of infection for only 1% of the exposed human populations. The uncertain
      variable, E. coli concentration accounted for approximately 92.1% in a typical
      scenario as the major contributing factor of the dose-response model. Resistant
      FIB in recreational waters that are exacerbated by a low dose of antibiotic
      pollutants would increase the adverse health effects in exposed human populations
      by 10 fold. 

PMID- 24328546
TI  - Bioefficacy, residue dynamics and safety assessment of the combination fungicide
      trifloxystrobin 25% + tebuconazole 50%-75 WG in managing early blight of tomato
      (Lycopersicon esculentum Mill.).
AB  - This paper reports the in vitro and in vivo bioefficacy of a combination
      fungicide trifloxystrobin (25%) + tebuconazole (50%) against early blight disease
      of tomato (Lycopersicon esculentum Mill.) caused by Alternaria solani and their
      corresponding pre-harvest intervals (PHI) with reference to the maximum residue
      limits (European Union). Bioefficacy of the test fungicide combination revealed
      that in vitro conditions manifested the best control (75.1%) at 350 mg kg(-1)
      against 76.2% control under field conditions. A sample preparation method based
      on ethyl acetate extraction and estimation by LC-MS multiple reaction monitoring
      (MRM) was validated in tomato fruits at 0.01 mg/kg and dissipation studies were
      conducted in field at single and double doses. The residues of both the compounds
      on all the sampling days were below the European Union maximum residue limits (EU
      MRLs) and the maximum permissible intakes (MPIs) were calculated on the basis of
      prescribed acceptable daily intake (ADI). The combined bioefficacy and residue
      dynamics information will support label-claim of this fungicide combination for
      the management of early blight in tomato.

PMID- 24328547
TI  - Neonatal screening for congenital cytomegalovirus infection in preterm and small
      for gestational age infants.
AB  - Congenital cytomegalovirus (CMV) infection affects many organs:
      reticuloendothelial and central nervous system are particularly involved.
      Congenital CMV infection is the leading cause of non-genetic sensorineural
      hearing loss. Hearing impairment can be present at birth or it can occur months
      or even years after birth. It is as well an important risk factor for antenatal
      stillbirth, preterm birth and small for gestational age (SGA) condition. For
      these reasons we should early identify congenital CMV infection investigating at
      least at risk newborns such as preterm or SGA babies given that a simple and
      standardized method for a large scale screening program is lacking. In our study,
      we found an association between congenital CMV infection and preterm births
      (3.03%) and with SGA condition (3.7%). Consequently, routine CMV urine detection
      should be performed at least in all babies born before 37 weeks of gestational
      age and in term SGA newborns.

PMID- 24328548
TI  - Cytokinesis-block micronucleus assay adapted for analyzing genomic instability of
      human mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) are multipotent cells used in cell therapy
      research. One of the problems involving hMSCs is the possibility of genetic
      instability during in vitro expansion required to obtain a suitable number of
      cells for clinical applications. The cytokinesis-block micronucleus (CBMN) assay
      measures genetic instability by analyzing the presence of micronucleus (MN),
      nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in binucleated cells. The
      present study describes modifications in the CBMN assay methodology to analyze
      genetic instability in hMSCs isolated from the umbilical vein and in vitro
      expanded. The best protocol to achieve binucleated hMSCs with preserved cytoplasm
      was as follows: cytochalasin B concentration (4.0 MUg/mL), use of hypotonic
      treatment (3 min), and the fixative solution (9 methanol:1 acetic acid). These
      adaptations were reproduced in three hMSC primary cell cultures and also in XP4PA
      and A549 cell lines. The frequency of hMSCs treated with mitomycin-C presenting
      MN was lower than that with other nuclear alterations, indicating that the hMSCs
      contain mechanisms to avoid a high level of chromosomal breaks. However, a high
      frequency of cells with NPBs was detected and spontaneous anaphase bridges under
      normal hMSC in vitro culture were observed. Considering that anaphase bridges are
      characteristic alterations in tumor cells, the CBMN assay is indicated as an
      important tool associated with other genetic analyses in order to ensure the safe
      clinical use of hMSCs in cell therapy.

PMID- 24328549
TI  - Axitinib for the treatment of advanced renal cell carcinoma.
AB  - INTRODUCTION: Advanced understanding of the pathogenesis of renal cell carcinoma
      (RCC) has led to development and approval of several molecularly targeted
      therapies since 2005. Axitinib is a potent and selective inhibitor of vascular
      endothelial growth factor receptors 1, 2 and 3. In the randomized Phase III AXIS
      trial, axitinib significantly prolonged progression-free survival compared with
      sorafenib, respectively (6.7 vs 4.7 months; p < 0.0001), and improved objective
      response rate (19 vs 9%; p = 0.0001), resulting in its approval for advanced or
      metastatic RCC after failure of one systemic therapy. However, overall survival
      was similar with axitinib and sorafenib. Common adverse events associated with
      axitinib include diarrhea, hypertension and fatigue. AREAS COVERED: The
      properties, clinical efficacy, adverse events, pharmacokinetics and
      pharmacodynamics of axitinib are summarized and its position in the overall
      therapeutic landscape for metastatic RCC among several targeted therapies is
      described. EXPERT OPINION: Axitinib is generally well-tolerated and provides
      definitive clinical benefits in patients with advanced or metastatic RCC as
      second-line therapy. However, as with other tyrosine kinase inhibitors of the
      same class, axitinib does not prolong overall survival; therefore, selection of
      second-line tyrosine kinase inhibitor therapy, including axitinib, must be
      carefully considered to maximize outcomes for each patient.

PMID- 24328550
TI  - Quality of life and functional outcomes 10 years after laparoscopic radical
      prostatectomy.
AB  - BACKGROUND: Minimally invasive laparoscopic radical prostatectomy (LRP) has
      proven equally effective as open surgery in terms of cancer control and
      peroperative complication rate with less bleeding and postoperative pain.
      However, long-term follow-up data after LRP are scarce, especially as related to
      quality of life (QoL). AIM: To compare QoL and functional outcomes at least 10
      years after LRP with a population-based control group matched for age and region.
      METHODS: Follow-up data were obtained by mailed questionnaires from patients who
      responded anonymously to five international questionnaires (EQ-5D, QLQ-C30, QLQ
      PR25, IPSS, and IIEF). We collected self-reported outcome data directly from 49
      patients who underwent LRP more than 10 years ago in our centre. The results of
      the patients' overall QoL and urinary continence rates were compared with 918
      controls matched for region and age. RESULTS: Forty-two patients (86%) and 808
      (88%) controls reported having no urinary leakage. Only 11 patients (24%) still
      had sexual activities 10 years after LRP, and three were without erectile
      dysfunction. There was no difference in four of five statements of the self
      assessed QoL questionnaires between the LRP and control group. Anxiety level was
      higher in the LRP group (44%) than in the control group (23%). CONCLUSION:
      Patients reported high self-assessed QoL, although they also reported low sexual
      activity 10 years after LRP. Prevalence of urinary leakage was similar in both
      groups. However, anxiety was more common in LRP patients.

PMID- 24328551
TI  - Dimethyloxaloylglycine increases the bone healing capacity of adipose-derived
      stem cells by promoting osteogenic differentiation and angiogenic potential.
AB  - Hypoxia inducible factor-1alpha (HIF-1alpha) plays an important role in
      angiogenesis-osteogenesis coupling during bone regeneration, which can enhance
      the bone healing capacity of mesenchymal stem cells (MSCs) by improving their
      osteogenic and angiogenic activities. Previous studies transduced the HIF-1alpha
      gene into MSCs with lentivirus vectors to improve their bone healing capacity.
      However, the risks due to lentivirus vectors, such as tumorigenesis, should be
      considered before clinical application. Dimethyloxaloylglycine (DMOG) is a cell
      permeable prolyl-4-hydroxylase inhibitor, which can activate the expression of
      HIF-1alpha in cells at normal oxygen tension. Therefore, DMOG is expected to be
      an alternative strategy for enhancing HIF-1alpha expression in cells. In this
      study, we explored the osteogenic and angiogenic activities of adipose-derived
      stem cells (ASCs) treated with different concentrations of DMOG in vitro, and the
      bone healing capacity of DMOG-treated ASCs combined with hydrogels for treating
      critical-sized calvarial defects in rats. The results showed that DMOG had no
      obvious cytotoxic effects on ASCs and could inhibit the death of ASCs induced by
      serum deprivation. DMOG markedly increased vascular endothelial growth factor
      production in ASCs in a dose-dependent manner and improved the osteogenic
      differentiation potential of ASCs by activating the expression of HIF-1alpha.
      Rats with critical-sized calvarial defects treated with hydrogels containing DMOG
      treated ASCs had more bone regeneration and new vessel formation than the other
      groups. Therefore, we believe that DMOG enhanced the angiogenic and osteogenic
      activity of ASCs by activating the expression of HIF-1alpha, thereby improving
      the bone healing capacity of ASCs in rat critical-sized calvarial defects. 

PMID- 24328552
TI  - Immuno-pathologic effects of oral administration of chlorpyrifos in broiler
      chicks.
AB  - This study sought to assess if chlorpyrifos (CPF) induced immunotoxic effects in
      orally-treated day-old broiler chicks. Groups of chicks received per os CPF
      diluted in xylene at 5, 10, and 20 mg/kg body weight (CPF-5, CPF-10, and CPF-20)
      orally daily for 15 days. Xylene and control groups received xylene alone (1
      ml/kg BW) and physiological saline, respectively. At various times during/after
      the exposure regimens, different immune end-points were analyzed in the birds.
      Humoral immunity was examined by assessing antibody responses to sheep red blood
      cells. Cell-mediated immunity was measured via lymphoproliferative responses to
      avian tuberculin. Leukocyte phagocytic ability was measured using a carbon
      clearance assay. Results showed that CPF administered to broiler chicks caused a
      dose-dependent decrease in humoral immunity, cell-mediated immunity, and
      phagocytic activity. Dose- and time-related pathological changes were observed in
      bursa of Fabricius, spleen, and thymus in treated birds. These changes were mild,
      moderate, and severe, respectively, in the 5, 10, and 20 mg/kg CPF groups. The
      Bursa of Fabricius in treated birds showed increased inter-follicular connective
      tissue proliferation, severe moderate cytoplasmic vacuolation, edema, and
      degenerative changes such as pyknosis and fragmentation of nuclei that depleted
      the follicles of lymphoid cells. In the spleen, disorganization of follicular
      patterns, severe congestion, cytoplasmic vacuolation, degenerative changes, and
      hyperplasia of reticular cells were noted. The thymus in treated birds exhibited
      congestion, hyper-cellularity, and a presence of immature monocytes in the
      medullary region, as well as myoid cell necrosis. Taken together, these studies
      clearly demonstrated that chlorpyrifos could induce immunotoxicities in broiler
      birds.

PMID- 24328553
TI  - Quality by design approach to understand the process of optimization of
      iloperidone nanostructured lipid carriers for oral bioavailability enhancement.
AB  - CONTEXT: The current work was carried out by exploring the principles of quality
      by design approach to develop an optimized nanostructured lipid carrier (NLC)
      formulation of poorly water soluble active iloperidone (ILO) through systematic
      statistical study. The potential of NLC for improving the oral bioavailability of
      ILO was also evaluated. OBJECTIVE: To understand the effect of formulation
      variables (critical parameters) on the performance characteristics (critical
      quality attributes) of NLC. MATERIALS AND METHODS: A 3-factor, 3-level Box
      Behnken factorial design was explored to predict the responses such as particle
      size (Y1) and % entrapment efficiency (EE) (Y2) when concentration of lipid (X1),
      concentration of drug (X2) and concentration of surfactant (X3) were selected as
      independent variables. RESULTS AND DISCUSSION: Particle size analysis revealed
      that all the batches were within the nanometer range. The % EE was found to be
      between 63% and 96%. In-vitro release study demonstrated sustained release
      profile of ILO NLC. The pharmacokinetic study in Wistar rats over the period of
      24 h demonstrated 8.30-fold increase in oral bioavailability of ILO NLC as
      compared with ILO pure drug suspension. CONCLUSION: The NLC formulation
      remarkably improved the oral bioavailability of ILO and demonstrated a promising
      perspective for oral delivery of poorly water-soluble drugs.

PMID- 24328556
TI  - Upregulation of human mammaglobin reduces migration and invasion of breast cancer
      cells.
AB  - Little is known about the biological role of human mammaglobin (hMAM) that is
      considered as a promising marker for breast cancer. Here, we investigated hMAM's
      role related to migration and invasion of human breast cancer cells (hBCC).
      Compared to normal cells, hBCC have high MAM mRNA expression levels. Of the hBCC
      tested, MAM mRNA expression levels were higher in noninvasive than in invasive
      cells. Overexpression of hMAM in breast cancer cells decreased migration and
      invasion, whereas knockdown of hMAM increased both. Taken together, these results
      suggest that metastasis of hBCC could be controlled by hMAM expression levels. 

PMID- 24328555
TI  - Temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme: a
      systematic review.
AB  - To systematically review the efficacy/safety of radiotherapy/temozolomide (TMZ)
      vs. radiotherapy for treating glioblastoma (GBM), Medline, Current Contents, and
      Cochrane database were searched. Five studies were reviewed. Median survival
      ranged from 9.4 to 19.0 months (radiotherapy/TMZ) vs. 7.3-17.1 months
      (radiotherapy). Survival ranged from 80.2% to 95.0% (radiotherapy/TMZ) vs. 8.3
      84.2% (radiotherapy) at 0.5 years and from 20.0% to 61.1% (radiotherapy/TMZ) vs.
      5.0-50.6% (radiotherapy) at 1 year. Median progression-free survival (PFS) ranged
      from 5.5 to 13.0 months (radiotherapy/TMZ) vs. 4.4-7.6 months (radiotherapy). PFS
      rates at 0.5 years ranged from 53.9-78.0% (radiotherapy/TMZ) vs. 53.9-78.0%
      (radiotherapy). Radiotherapy/TMZ provides better survival outcomes than
      radiotherapy alone in treating GBM. 

PMID- 24328557
TI  - Blockage of STAT3 signaling pathway with a decoy oligodeoxynucleotide inhibits
      growth of human ovarian cancer cells.
AB  - Transcription factor decoy oligodeoxynucleotides (ODN) represent a novel tool for
      targeted inhibition of the STAT3 signaling pathway. To investigate its
      therapeutic potential in ovarian cancer, a double-stranded decoy ODN mimicking
      STAT3-specific cis-elements was transfected into two ovarian cancer cell lines
      OVCAR3 and SKOV3. The STAT3 decoy ODN treatment specifically blocked STAT3
      signaling, and inhibited cell proliferation by inducing apoptosis and cell cycle
      arrest. These results suggest that targeted blockade of the STAT3 signaling
      pathway with a decoy ODN may represent a potential therapeutic approach in the
      treatment of ovarian cancer. 

PMID- 24328554
TI  - Retinal ligand mobility explains internal hydration and reconciles active
      rhodopsin structures.
AB  - Rhodopsin, the mammalian dim-light receptor, is one of the best-characterized G
      protein-coupled receptors, a pharmaceutically important class of membrane
      proteins that has garnered a great deal of attention because of the recent
      availability of structural information. Yet the mechanism of rhodopsin activation
      is not fully understood. Here, we use microsecond-scale all-atom molecular
      dynamics simulations, validated by solid-state (2)H nuclear magnetic resonance
      spectroscopy, to understand the transition between the dark and metarhodopsin I
      (Meta I) states. Our analysis of these simulations reveals striking differences
      in ligand flexibility between the two states. Retinal is much more dynamic in
      Meta I, adopting an elongated conformation similar to that seen in the recent
      activelike crystal structures. Surprisingly, this elongation corresponds to both
      a dramatic influx of bulk water into the hydrophobic core of the protein and a
      concerted transition in the highly conserved Trp265(6.48) residue. In addition,
      enhanced ligand flexibility upon light activation provides an explanation for the
      different retinal orientations observed in X-ray crystal structures of active
      rhodopsin. 

PMID- 24328558
TI  - Can transcriptomics provide insight into the chemopreventive mechanisms of
      complex mixtures of phytochemicals in humans?
AB  - Blueberries contain relatively large amounts of different phytochemicals, which
      are suggested to have chemopreventive properties, but little information is
      available on the underlying molecular modes of action. This study investigates
      whole genome gene expression changes in lymphocytes of 143 humans after a 4-week
      blueberry-apple juice dietary intervention. Differentially expressed genes and
      genes correlating with the extent of antioxidant protection were identified in
      four subgroups. The magnitude of the preventive effect after the intervention
      differed between these four subgroups. Furthermore, subjects in two groups
      carried genetic polymorphisms that were previously found to influence the
      chemopreventive response. Pathway analysis of the identified genes showed strong
      but complex gene expression changes in pathways signaling for apoptosis, immune
      response, cell adhesion, and lipid metabolism. These pathways indicate increased
      apoptosis, upgraded growth control, induced immunity, reduced platelet
      aggregation and activation, blood glucose homeostasis, and regulation of fatty
      acid metabolism. Based on these observations, we hypothesize that combining
      transcriptomic data with phenotypic markers of oxidative stress may provide
      insight into the relevant cellular processes and genetic pathways, which
      contribute to the antioxidant response of complex mixtures of phytochemicals,
      such as found in blueberry-apple juice.

PMID- 24328559
TI  - Anxiety and anxiety sensitivity as predictors of fear of childbirth: different
      patterns for nulliparous and parous women.
AB  - OBJECTIVE: The demographic characteristics, maternal parity and personal traits
      of pregnant women have been frequently studied predictors of fear of childbirth
      (FOC). The aim of this study was to examine the role of demographic variables,
      expected pain level, trait anxiety and anxiety sensitivity in FOC among
      nulliparous and multiparous women in the last trimester of pregnancy. METHOD: Two
      hundred pregnant women completed a booklet with questionnaires including the
      Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ), Anxiety Sensitivity
      Index (ASI), The State - Trait Anxiety Inventory (STAI) and questions on expected
      labor pain and demographics. RESULTS: Results showed that FOC was higher amongst
      nulliparous women, but FOC level was not associated with other demographic
      variables. Different predictors were established in nulliparous and multiparous
      women. While higher intensity of expected labor pain and anxiety sensitivity
      (dimension physical concern) were significant predictors in both groups, trait
      anxiety was significant for the first-time mothers only. CONCLUSION: Amongst all
      women, anxiety sensitivity (physical concerns dimension) was identified as an
      important vulnerability factor for FOC. As such, the level of anxiety
      sensitivity, and any resulting fear or expectations of pain, should be assessed
      in expectant mothers by clinicians in prenatal settings. Furthermore, anxiety
      sensitivity should be an important target for psychological interventions aimed
      at managing FOC.

PMID- 24328560
TI  - Rhodium(II)-catalyzed alkyne amination of homopropargylic sulfamate esters:
      stereoselective synthesis of functionalized norcaradienes by arene
      cyclopropanation.
AB  - A rhodium(II) catalyzed nitrene-alkyne cycloaddition of stereochemically well
      defined homopropargylic ethers is followed by arene cyclopropanation to afford
      unique tetracyclic norcaradiene products bearing a cyclic sulfamate. Products
      from the arene cyclopropanation (Buchner reaction) can be converted to fused
      cycloheptatrienes via a ring enlarging electrocyclization after nucleophilic ring
      opening of the cyclic sulfamate ester. 

PMID- 24328561
TI  - Identification of a novel synonymous mutation in the human beta -Ureidopropionase
      Gene UPB1 affecting pre-mRNA splicing.
AB  - beta-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway
      and it catalyzes the conversion of N-carbamyl-beta-alanine and N-carbamyl-beta
      aminoisobutyric acid to beta-alanine and beta-aminoisobutyric acid, respectively,
      and ammonia and CO2. To date, only 16 genetically confirmed patients with a
      complete beta-ureidopropionase deficiency have been reported. Here, we report the
      clinical, biochemical, and molecular analysis of a newly identified patient with
      beta-ureidopropionase deficiency. Mutation analysis of the UPB1 gene showed that
      the patient was compound heterozygous for a novel synonymous mutation c.93C >T
      (p.Gly31Gly) in exon 1 and a previously described missense mutation c.977G >A
      (p.Arg326Gln) in exon 9. The in silico predicted effect of the synonymous
      mutation p.Gly31Gly on pre-mRNA splicing was investigated using a minigene
      approach. Wild-type and the mutated minigene constructs, containing the entire
      exon 1, intron 1, and exon 2 of UPB1, yielded different splicing products after
      expression in HEK293 cells. The c.93C >T (p.Gly31Gly) mutation resulted in
      altered pre-mRNA splicing of the UPB1 minigene construct and a deletion of the
      last 13 nucleotides of exon 1. This deletion (r.92_104delGCAAGGAACTCAG) results
      in a frame shift and the generation of a premature stop codon (p.Lys32SerfsX31).
      Using a minigene approach, we have thus identified the first synonymous mutation
      in the UPB1 gene, creating a cryptic splice-donor site affecting pre-mRNA
      splicing. 

PMID- 24328562
TI  - Chemoenzymatic synthesis of 3'-deoxy-3'-(4-substituted-triazol-1-YL)-5
      methyluridine.
AB  - An efficient protocol has been developed for the synthesis of a small library of
      3'-deoxy-3'-(4-substituted-triazol-1-yl)-5-methyluridine using Cu(I)-catalyzed
      Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition reaction of 3'-azido-3'-deoxy
      5-methyluridine with different alkynes under optimized condition in an overall
      yields of 76%-92%. Here, the azido precursor compound, i.e., 3'-azido-3'-deoxy-5
      methyluridine was chemoenzymatically synthesized from D-xylose in good yield.
      Some of the alkynes used in cycloaddition reaction were synthesized by the
      reaction of hydroxycoumarins or naphthols with propargyl bromide in acetone using
      K2CO3in excellent yields. All synthesized compounds were unambiguously identified
      on the basis of their spectral (IR, (1)H-, (13)C NMR spectra, and high-resolution
      mass spectra) data analysis. 

PMID- 24328563
TI  - Probing the site-selective binding of an antiretroviral drug, Stavudine to calf
      thymus DNA.
AB  - The interaction of an anti-HIV drug, stavudine (STV) with calf thymus
      deoxyribonucleic acid (DNA) was investigated employing acridine orange (AO) as a
      fluorescence probe. Spectroscopic investigations revealed the intercalative mode
      of binding of STV to DNA. The analysis of fluorescence data indicated the
      presence of static quenching mechanism between STV and DNA. Thermodynamic
      parameters indicated the presence of van der Waals forces in addition to
      intercalative mode of binding. CD data revealed the partial B -> A conformational
      transition of DNA upon intercalative mode of binding with STV.

PMID- 24328565
TI  - Design, synthesis, antiviral, and cytostatic evaluation of novel isoxazolidine
      analogues of C-nucleotides.
AB  - 5-Aryl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesised from N
      methyl-C-diethoxyphosphorylnitrone and vinyl aryls in good yields. Isoxazolidine
      phosphonates obtained herein were evaluated for activity against a broad range of
      DNA and RNA viruses. None of the compounds were endowed with antiviral activity
      nor cytostatic activity at 100 to 250 MUM concentrations.

PMID- 24328564
TI  - 5'-deoxy-5'-hydrazinylguanosine as an initiator of T7 Rna polymerase-catalyzed
      transcriptions for the preparation of labeling-ready RNAs.
AB  - 5'-deoxy-5'-hydrazinylguanosine was incorporated into the 5'-termini of RNA
      transcripts using T7 RNA polymerase. Transcriptions provided 5'-hydrazinyl-RNA
      that was readily labeled and purified. The use of fluorophore-labeled material
      was validated in an endoribonuclease activity assay. 

PMID- 24328568
TI  - Relation of antimullerian hormone with the clinical signs of hyperandrogenism and
      polycystic ovary morphology.
AB  - The relation of antimullerian hormone (AMH) levels with the clinical and
      biochemical markers of polycystic ovary syndrome (PCOS) could be different. A
      total of 463 PCOS patients were evaluated in this cross-sectional study. Groups
      were constructed according to polycystic ovarian morphology (PCOM) and menstrual
      cycle-length. The relation of serum AMH with androgenic hormones, menstrual cycle
      length and clinical signs of PCOS were investigated. A powerful positive relation
      was found between the PCOM and AMH levels (odds ratio = 2.49). There was a
      negative correlation between age and AMH level (p < 0.001, r[correlation
      coefficent] = -0.155). Positive correlations were found between luteinizing
      hormone (LH) and AMH (p < 0.001, r = 0.25) and also between cycle length and AMH
      (p < 0.01, r = 0.27). We found a negative week correlation between AMH and
      follicle-stimulating hormone (FSH) (p = 0.01, r = -0.19). After controlling main
      androgenic hormones, AMH was found to be correlated with the Ferriman-Gallway
      score (p = 0.03, r = 0.18). There was a positive relationship between hirsutism
      and AMH (odds ratio = 1.43), but no correlation between AMH and other parameters
      of clinical hyperandrogenism like hair-loss, acne and seborrhea were identified.
      The strongest relation was presented between the AMH levels and PCOM. Also, cycle
      length correlated well with the AMH levels. The relationship between hirsutism
      and AMH is found to be independent from androgenic hormones.

PMID- 24328569
TI  - Bestrophin 1--Phenotypes and Functional Aspects in Bestrophinopathies.
AB  - This is to review the current state of knowledge on the functional and clinical
      aspects of bestrophin 1, a prominent member of a family of proteins involved in
      the control and properties of the light peak of the EOG. Initially human
      bestrophin 1 gene (BEST1) mutations were identified to underlie Best vitelliform
      macular dystrophy (VMD), a dominantly inherited, juvenile-onset form of macular
      degeneration. In the recent past the phenotypical spectrum of retinal disorders
      associated with BEST1 mutations has been extended and the term bestrophinopathies
      was coined. The physiological role of bestrophin 1 is still not completely
      understood but has been linked to the generation of a transepithelial chloride
      current by controlling voltage-dependent calcium channels (VDCC). Dysfunction of
      bestrophin 1 may result in abnormal ion and fluid transport by the retinal
      pigment epithelium (RPE) disturbing and even disrupting direct interactions
      between the RPE and the photoreceptors. 

PMID- 24328570
TI  - High-modulus, high-conductivity nanostructured polymer electrolyte membranes via
      polymerization-induced phase separation.
AB  - The primary challenge in solid-state polymer electrolyte membranes (PEMs) is to
      enhance properties, such as modulus, toughness, and high temperature stability,
      without sacrificing ionic conductivity. We report a remarkably facile one-pot
      synthetic strategy based on polymerization-induced phase separation (PIPS) to
      generate nanostructured PEMs that exhibit an unprecedented combination of high
      modulus and ionic conductivity. Simple heating of a poly(ethylene oxide)
      macromolecular chain transfer agent dissolved in a mixture of ionic liquid,
      styrene and divinylbenzene, leads to a bicontinuous PEM comprising
      interpenetrating nanodomains of highly cross-linked polystyrene and poly(ethylene
      oxide)/ionic liquid. Ionic conductivities higher than the 1 mS/cm benchmark were
      achieved in samples with an elastic modulus approaching 1 GPa at room
      temperature. Crucially, these samples are robust solids above 100  degrees C,
      where the conductivity is significantly higher. This strategy holds tremendous
      potential to advance lithium-ion battery technology by enabling the use of
      lithium metal anodes or to serve as membranes in high-temperature fuel cells. 

PMID- 24328571
TI  - Radical acylation of L-lysine derivatives and L-lysine-containing peptides by
      peroxynitrite-treated diacetyl and methylglyoxal.
AB  - Highly electrophilic alpha-dicarbonyls such as diacetyl, methylglyoxal, 3
      deoxyglucosone, and4,5-dioxovaleric acid have been characterized as secondary
      catabolites that can aggregate proteins and form DNA nucleobase adducts in
      several human maladies, including Alzheimer's disease, rheumatoid arthritis,
      diabetes, sepsis, renal failure, and respiratory distress syndrome. In vitro,
      diacetyl and methylglyoxal have also been shown to rapidly add up the
      peroxynitrite anion (k2 ~ 10(4)-10(5) M(-1) s(-1)), a potent biological
      nucleophile, oxidant and nitrosating agent, followed by carbon chain cleavage to
      carboxylic acids via acetyl radical intermediate that can modify amino acids. In
      this study, we used the amino acid derivatives Ac-Lys-OMe and Z-Lys-OMe and
      synthesized the tetrapeptides H-KALA-OH, Ac-KALA-OH, and H-K(Boc)ALA-OH to reveal
      the preferential Lys amino group targeted by acyl radical generated by the alpha
      dicarbonyl/peroxynitrite system. The pH profiles of the reactions are bell
      shaped, peaking at approximately 7.5; hence, they are close to the pKa values of
      ONOOH and of the catalytic H2PO4(-) anion. RP-HPLC and ESI-MS analyses of
      reaction products confirmed (alpha)N- and (epsilon)N-acetylation of Lys by
      diacetyl as well as acetylation and formylation by methylglyoxal, with preference
      for the alpha-amino group. These data suggest the possibility of radical
      acylation of proteins in epigenetic processes, where enzymatic acetylation of
      these biomolecules is a well-documented event, recently reported to be as
      critical to the cell cycle as phosphorylation. Also noteworthy is the observed
      formylation of L-Lys containing peptides by methylglyoxal never reported to occur
      in amino acid residues of peptides and proteins.

PMID- 24328572
TI  - Hepatocyte targeting using pegylated asialofetuin-conjugated liposomes.
AB  - Abstract Background and purpose: The hepatocyte asialoglycoprotein receptor
      mediates uptake of desiaylated glycoproteins by receptor-mediated endocytosis.
      This work explores a hepatocyte-specific targeting strategy using asialofetuin
      (AF) covalently coupled to pegylated liposomes. Methods: AF was conjugated to the
      distal end of polyethylene glycol-functionalized phospholipids. Chemical
      modification of AF did not interfere with its receptor interaction. AF-liposomes
      had a size of less than 130 nm, were judged to be monodisperse and were labelled
      with fluorescent organic dyes or loaded with quantum dots. Results: In vitro,
      binding and cellular uptake of fluorescent AF-liposomes by HepG2 hepatocellular
      carcinoma cells were reduced at low temperature and could be competitively
      inhibited by an excess of unbound AF. Hepatocyte-specific targeting and
      internalization of AF-liposomes in vivo was confirmed in the rat and could be
      competitively inhibited by co-injection of unbound AF. In contrast, non-pegylated
      liposomes accumulated in cells of the reticuloendothelial system such as hepatic
      Kupffer cells and spleen after intravenous administration. Conclusion: We
      conclude that the use of AF-conjugated, pegylated liposomes is a promising
      strategy to avoid the reticuloendothelial system and specifically target
      hepatocytes via the asialoglycoprotein receptor in vitro as well as in vivo.

PMID- 24328573
TI  - Biomechanical impact of posterior glenoid wear on anatomic total shoulder
      arthroplasty.
AB  - INTRODUCTION: This study quantified bone removed to correct three different sizes
      of posterior glenoid defects and also quantified the change in rotator cuff
      muscle length resulting from correction of each defect using three different
      glenoid designs. METHODS: A 3-D computer model quantified the cortical and
      cancellous bone removed when correcting three sizes of posterior glenoid defects
      and simulated internal/external rotation to quantify changes in rotator cuff
      muscle length when correcting glenoid retroversion in three sizes of posterior
      glenoid defects using three different glenoid prostheses: 1. eccentric reaming
      using a non-augmented glenoid (Equinoxe standard pegged), 2. 8 degrees , 12
      degrees , and 16 degrees  Equinoxe posterior augment glenoid (wedge), and 3. 3
      mm, 5 mm, and 7 mm Global Step-Tech posterior augment glenoid (step). RESULTS:
      For small defects, the 8 degrees  wedge and 3 mm step posterior augment glenoids
      conserves 50% (1.295 cm 3 ) and 23% (1.704 cm 3 ) more bone than eccentric
      reaming (2.147 cm 3 ), respectively. For medium defects, the 12 degrees  wedge
      and 5 mm step glenoids conserves 69% more (1.295 cm 3 ) and 2% less (2.720 cm 3 )
      bone than eccentric reaming (2.655 cm 3 ), respectively. For large defects, the
      16 degrees  wedge and 7 mm step glenoids conserve 48% more (1.852 cm 3 ) and 36%
      less (4.343 cm 3 ) bone than eccentric reaming (3.736 cm 3 ), respectively. For
      each size defect, muscle shortening was observed for both eccentric reaming and
      each augmented glenoid design. Eccentric reaming medialized the humerus and
      resulted in additional muscle shortening (wedge: 2.0%, 2.9%, and 3.6%; step:
      1.2%, 1.7%, and 1.7%) in each size defect, respectively. DISCUSSION AND
      CONCLUSIONS: Both step and wedge augmented glenoid designs conserved more
      anterior glenoid bone and were associated with less muscle shortening than
      correction with eccentric reaming. However, wedge posterior augment glenoids
      medialized the humerus less and were observed to be more bone conserving than
      step posterior augment glenoids, particular in large glenoid defects.

PMID- 24328574
TI  - Reverse shoulder glenoid loosening: an evaluation of the initial fixation
      associated with six different reverse shoulder designs.
AB  - INTRODUCTION: This study quantified glenoid fixation before and after cyclic
      loading of six reverse shoulder prosthesis designs when secured to low and high
      density bone substitute blocks. METHODS: A displacement test quantified fixation
      of six reverse shoulder designs: 38 mm Equinoxe standard offset (EQ), 38 mm
      Equinoxe lateral offset (EQL), 36 mm Depuy Delta III (DRS), 36 mm Zimmer (ZRS),
      32 mm DJO RSP (DJO), and a 36 mm Tornier BIO-RSA (BIO), secured to 0.24 and 0.48
      g/cm 3 polyurethane blocks as a shear (357 N) and compressive (50 N) load were
      applied before and after cyclic loading. Displacement was measured with a dial
      indicator in the directions of the applied loads along the superior/inferior
      axis. A cyclic test rotated each glenosphere (N= 7) at 0.5 Hz for 10 k cycles as
      750 N was constantly applied. A two-tailed Student's unpaired t-test compared
      mean displacements. RESULTS: The average displacement of the EQ, EQL, ZRS, DJO,
      DRS, and BIO-RSA devices in the low density substrate was 182, 137, 431, 321,
      190, and 256 microns, respectively. The average displacement of the EQ, EQL, ZRS,
      DRS, and BIO-RSA devices in the high density substrate was 102, 95, 244, 138, and
      173 microns, respectively. Pre- and post-cyclic displacement was significantly
      less in the high density bone substitutes than in the low density bone
      substitutes for the majority of implant comparisons. During the cyclic test, six
      of seven ZRS devices failed at an average of 2,603 cycles, one of seven 32 mm DJO
      failed at 7,342 cycles, and four of seven BIO devices failed at an average of
      2,926 cycles. All seven of the EQ, EQL, and DRS devices remained well fixed
      throughout cyclic loading. DISCUSSION AND CONCLUSIONS: This study quantified
      glenoid fixation of six reverse shoulder designs; significant differences in
      fixation were observed between nearly every implant design tested.

PMID- 24328575
TI  - Design rationale for a posterior/superior offset reverse shoulder prosthesis.
AB  - INTRODUCTION: A computer model quantified and compared muscle lengths and moment
      arms of two different reverse shoulder arthroplasty humeral tray designs during
      two different motions. METHODS: The computer model simulated internal/ external
      rotation and abduction in the scapular plane for the normal shoulder, the 38 mm
      non-offset, and the 38 mm posterior-superior offset reverse shoulders. Muscle
      lengths were directly measured for seven muscles during each motion. External
      rotation moment arms were calculated for five muscles during each motion.
      RESULTS: The offset tray shifted the humerus posteriorly and superiorly relative
      to the non-offset tray. The more superior humeral position with the offset tray
      elongated the deltoid 1.0% to 3.8% less and caused each muscle to convert from an
      adductor to abductor earlier in abduction. The more posterior humeral position
      with the offset tray better restored the anatomic muscle tension, decreased the
      internal rotation capability (e.g., moment arm) of the subscapularis and teres
      major by 7.1 mm and 9.5 mm, and increased the external rotation capability of the
      posterior deltoid, infraspinatus, and teres minor by 1.3 mm, 8.6 mm, and 7.8 mm.
      DISCUSSION AND CONCLUSIONS: The offset humeral tray bet- ter restored the
      anatomic muscle tensioning and increased the external rotation moment arms
      relative to the non-offset humeral tray, which has positive implications on
      strength, stability, and motion.

PMID- 24328576
TI  - Muscle force and excursion requirements and moment arm analysis of a posterior
      superior offset reverse total shoulder prosthesis.
AB  - Current reverse total shoulder arthroplasty prosthesis designs do not permit
      offset of the humerus in the sagittal plane. Posteriorly shifting the humerus has
      the theoretical benefit of lengthening the infraspinatus and teres minor muscles
      and their external rotation moment arms, thereby improving the tension and
      efficiency of each external rotator and subsequently requiring each muscle to
      produce less force to rotate the arm. A cadaveric shoulder controller was used to
      quantify the impact of a novel posterior-superior offset reverse shoulder
      prosthesis on muscle length, moment arms, and muscle forces relative to a non
      offset reverse shoulder design during two different motions: scapular plane
      abduction and internal/external rotation. The results of this study demonstrate
      that both the non-offset and offset reverse shoulder designs had similar force
      and excursion demands of the infraspinatus and teres minor muscles during both
      scapular abduction and internal and external rotation. Additionally, the offset
      reverse shoulder design was associated with significantly less over-tensioning of
      the middle and posterior deltoid and significantly more anatomic tensioning of
      the teres minor than the non-offset design. However, the offset reverse shoulder
      was observed to have more impingement than the non-offset design. These findings
      support the feasibility of this design: by restoring a more anatomic resting
      length to the deltoid and teres minor, the posterior-superior offset rTSA design
      may provide better teres minor function and rotational strength and may decrease
      the incidence of acromial stress fractures relative to the non-offset design.
      Clinical follow-up is required to confirm these findings.

PMID- 24328577
TI  - Effect of prosthesis design on muscle length and moment arms in reverse total
      shoulder arthroplasty.
AB  - The purpose of this article is to compare the effect reverse shoulder design
      philosophy has on the lengths and moment arms of the external rotators of the
      shoulder (i.e. posterior deltoid, infraspinatus, and teres minor). In this study,
      a single bone model was used to normalize the origin and insertion of each
      muscle. Four different commercially available designs were virtually implanted
      into the bones. The assemblies oriented with the arm at the side (0 degrees  of
      abduction) and articulated to 45 degrees  internal rotation and 45 degrees 
      external rotation. The muscle length and moment arm for each muscle were analyzed
      and compared to the anatomic shoulder. The results indicate that all the external
      rotators are shortened relative to the anatomic shoulder, but the MGLH design
      shortened the muscles the least. The moment arm analysis showed the teres minor
      and infraspinatus moment arms increased relative to the normal shoulder in
      external rotation for all designs. The moment arms are sensitive to the lateral
      offset of the stem relative to the center of rotation. The MGLH design had the
      largest moment arm during the external rotation range of motion due to its large
      humeral offset.

PMID- 24328578
TI  - Comparison of bone removed with reverse total shoulder arthroplasty.
AB  - INTRODUCTION: A computer model quantified glenoid base - plate surface contact
      area and the amount of humeral and glenoid bone removed by three different
      reverse shoulder prosthesis designs when implanted with various techniques.
      METHODS: The computer model quantified differences in glenoid baseplate contact
      area and the cortical and cancellous humeral and glenoid bone removed to implant
      the 36 mm Depuy Delta III, 32 mm neutral DJO RSP, and the 38 mm Exactech Equinoxe
      reverse shoulders when each was implanted along the inferior glenoid rim of a
      normal and 10 mm medially eroded scapula in 20 degrees  of humeral retroversion.
      The impact of inferior glenoid tilt was also quantified. RESULTS: The Delta III
      resected the most overall humeral bone (47.4 cm 3 ), the 32 mm RSP the second
      most (38.0 cm 3 ), and the Equinoxe the least (31.7 cm 3 ). The 32 mm RSP reamed
      away the most glenoid bone (3.7 cm 3 ), the Delta III the second most (3.6 cm 3
      ), and the Equinoxe the least (3.3 cm 3 ), with greater bone removed with
      inferior tilt. The Equinoxe had the most glenoid baseplate surface contact (501.3
      mm 2 ), the RSP had the second most (386.0 mm 2 ), and the Delta III had the
      least (360.6 mm 2 ), with less surface contact occurring with medial wear.

PMID- 24328579
TI  - Use of a caged, bone ingrowth, glenoid implant in anatomic total shoulder
      arthroplasty technique and early results.
AB  - Shoulder arthroplasty represents one of the fastest growing orthopaedic
      procedures in the USA. In comparison to hemiarthroplasty, total shoulder
      arthroplasty has higher patient satisfaction and lower revision rates. Aseptic
      glenoid loosening remains a concern for longevity of total shoulder
      arthroplasties. Cement fixation on the glenoid side represents the primary and
      only mode of fixation in the majority of implants in the USA. Metal backed
      glenoid designs have demonstrated higher failure rates, primarily due to thinning
      of the polyethylene bearing surface. We reviewed our early experience and results
      with a novel glenoid design. Long-term fixation in this design is provided by a
      central metallic bone ingrowth cage, without the need for metal backing.

PMID- 24328580
TI  - Addressing glenoid erosion in anatomic total shoulder arthroplasty.
AB  - Glenoid wear is common in the setting of shoulder arthritis. Severe glenoid
      erosion presents a serious challenge to the surgeon performing a shoulder
      arthroplasty. This paper presents the various classification schemes for glenoid
      erosion. The results of the six main treatment options for shoulder arthroplasty
      with an eroded glenoid are reviewed. The six treatment options include: 1.
      eccentric reaming, 2. bone grafting, 3. use of inset glenoid, 4. use of an
      augmented (asymmetric) glenoid component, 5. hemiarthroplasty, and 6. reverse
      shoulder arthroplasty. A treatment algorithm is proposed based on the amount of
      glenoid erosion. Severe glenoid wear resulting in the need for shoulder
      replacement surgery is a challenge; however, new tools for dealing with this
      complicated entity are rapidly evolving, including the use of augmented anatomic
      glenoid components and reverse shoulder arthroplasty with augmented baseplates.

PMID- 24328581
TI  - Addressing glenoid erosion in reverse total shoulder arthroplasty.
AB  - Severe glenoid wear is technically problematic, has a higher complication rate,
      and inferior results in the setting of shoulder arthroplasty. This paper
      introduces four basic strategies for treating glenoid erosion with a reverse
      shoulder arthroplasty which include; 1. eccentric reaming, 2. bone grafting of
      glenoid, 3. reaming and bone grafting, and 4. using augmented baseplates. The
      benefits and shortcomings of each of these techniques are discussed. The reverse
      shoulder arthroplasty has many advantages over anatomic shoulder arthroplasty
      when dealing with severe glenoid defects. Augmented baseplates are new and allow
      the surgeon to treat various different glenoid defects with preservation of
      glenoid subchondral bone.

PMID- 24328582
TI  - Open reduction internal fixation for proximal humerus fractures indications,
      techniques, and pitfalls.
AB  - Proximal humerus fractures account for approximately 5% of all fractures. It is
      estimated that due to our aging population, orthopaedic surgeons will see a three
      fold increase in proximal humerus fractures over the next 30 years. Internal
      fixation with locked plating is the current mainstay of treatment for
      functionally active patients who desire minimal loss of function. A thorough
      understanding of the indications, techniques, and drawbacks of treatment with
      internal fixation is essential to achieve the highest quality of patient care.

PMID- 24328583
TI  - Hemiarthroplasty for proximal humeral fractures. Indications, pitfalls, and
      technique.
AB  - Complex displaced proximal humerus fractures are frequently treated with a
      fracture prosthesis. This paper outlines the indications, introduces various
      fracture prostheses, describes the surgical technique, and rehabilitation for
      treatment of proximal humerus fractures with a fracture prosthesis
      hemiarthroplasty. Outcomes are noted to be improved when near anatomic humeral
      head height, and retroversion is obtained using a small body proximal humeral
      replacing implant designed for fracture treatment. The use of a common platform
      stem allows for relatively easy conversion to a reverse shoulder arthroplasty if
      tuberosity nonunion should occur.

PMID- 24328584
TI  - Indications, technique, and pitfalls of reverse total shoulder arthroplasty for
      proximal humerus fractures.
AB  - Management of proximal humerus fractures with hemiarthroplasty has been shown to
      yield unpredictable and inconsistent outcomes. Risk factors for clinical failure
      following hemiarthroplasty include postoperative tuberosity failure, advanced
      age, female sex, osteoporosis, and inability or unwillingness to participate in
      the extensive rehabilitation required. In this difficult-to-manage injury,
      reverse total shoulder arthroplasty (rTSA) for fracture has been shown to
      reliably restore elevation, even in cases of tuberosity failure, and to restore
      rotational movements if the tuberosity heals. In addition, a fracture-specific
      implant design has been suggested to improve the likelihood of tuberosity
      healing. Early results indicate that fractures of the proximal humerus that are
      indicated for arthroplasty should be considered for rTSA. Tuberosity integrity
      appears to impact rotational movement but not restoration of elevation.

PMID- 24328585
TI  - Revision of the loose glenoid component in anatomic total shoulder arthroplasty.
AB  - Loosening of the glenoid component is a frequent cause of failure of total
      shoulder arthroplasty (TSA). The etiology of glenoid component loosening is
      multifactorial and includes aseptic osteolysis, rotator cuff insufficiency, soft
      tissue instability, and infection. A loose glenoid component is frequently
      associated with a substantial loss of glenoid bone, which necessitates additional
      procedures to implant a new component. Several studies have shown that patients
      with a new glenoid component have better clinical outcomes, which makes
      successful glenoid reimplantation a priority. The reconstructive options when
      facing a loose glenoid component in anatomic total shoulder arthroplasty include
      the established techniques of reaming the high side or bone grafting the
      deficient glenoid combined with a one or two stage revision. Augmented glenoid
      components may allow surgeons to limit eccentric reaming or the extent of bone
      grafting necessary in a bone deficient glenoid. The reverse total shoulder
      arthroplasty (rTSA) is emerging as a useful reconstructive option capable of
      addressing bony and soft tissue problems encountered in revision TSA. The ream
      and-run procedure remains the least desirable option in the face of significant
      glenoid bone deficiency. The increasing use of augmented glenoids and rTSA in
      revision TSA may provide opportunities for new areas of clinical outcomes
      research in this challenging reconstructive problem.

PMID- 24328586
TI  - Revision of humeral components in shoulder arthroplasty.
AB  - Revision of a shoulder arthroplasty often requires removal of a well fixed
      humeral component. Revision of this component can be quite easy in the case of a
      non-infected platform stem or be very difficult when removal of a well cemented
      or on-growth stem with distal texturing is required. The purpose of this paper is
      to provide a series of techniques designed for revision of the humeral component
      in shoulder arthroplasty. Revision of the stem can be easy with a non-infected
      platform stem only requiring exchange of the epiphyseal component. Some stems,
      usually uncemented, can readily be removed from a proximal only approach. Stems
      with excellent cement mantles may require a longitudinal only split in the
      humerus done with minimal stripping of the brachialis. If complete cement removal
      is needed for infection or there is distal stem on growth, then a vascularized
      door technique is indicated. These techniques are explained in detail in this
      manuscript.

PMID- 24328587
TI  - Combined latissimus dorsi and teres major tendon transfers for external rotation
      deficiency in reverse shoulder arthroplasty.
AB  - Treatment of rotator cuff deficient shoulders continues to evolve. Reverse total
      shoulder arthroplasty has proven effective for restoring forward elevation and
      abduction in patients who suffer from pseudoparalysis secondary to rotator cuff
      insufficiency. Unfortunately, reverse total shoulder arthroplasty is less
      effective at restoring lost external rotation function in patients with deficient
      posterior rotator cuff tissue. Therefore, functional results of reverse
      arthroplasty in patients who demonstrate preoperative lag signs is inferior to
      patients with functioning posterior rotator cuff musculature. Combined latissimus
      dorsi and teres major tendon transfers have been shown to be effective treatment
      for patients with isolated loss of external rotation. These transfers have also
      been shown to improve functional results in patients who undergo reverse
      arthroplasty and have combined loss of forward elevation and external rotation
      preoperatively. Previously published studies have evaluated the combined reverse
      arthroplasty and tendon transfer procedure only in patients with first generation
      (medial center of rotation) implants. We reviewed our experience with the
      combined procedure utilizing a third generation (medial center of rotation
      glenoid and lateral center of rotation humerus) device.

PMID- 24328588
TI  - Evaluation and treatment of the infected shoulder arthroplasty.
AB  - Infection after shoulder arthroplasty remains one of the most common
      postoperative complications. Treatment options range from debridement,
      appropriate antibiotic regimen, and retaining the implant to resection
      arthroplasty in the elderly medically challenged patient. We review the
      diagnostic challenges and treatment options for periprosthetic infections
      involving the shoulder. It appears that early detection, isolation of the
      infecting organism, and aggressive debridement with appropriate antibiotic
      treatment is the most important component of a successful treatment program
      designed to eradicate the infection. This early treatment which in most cases is
      combined with a two-stage approach (with an interim antibiotic spacer) provides
      the best opportunity to obtain a reasonably painless and functional shoulder
      arthroplasty.

PMID- 24328589
TI  - Use of the subscapularis preserving technique in anatomic total shoulder
      arthroplasty.
AB  - Subscapularis tenotomy for total shoulder arthroplasty has been the standard
      approach for shoulder surgeons that utilize the deltopectoral approach. The risk
      of subscapularis insufficiency after this approach has been well documented. In
      order to avoid subscapularis complications, Lafosse reported a technique for
      total shoulder arthroplasty that utilizes a trans-deltoid approach through the
      rotator interval that yielded satisfactory clinical outcomes. However, he also
      reported concerns about humeral head undersizing and inadequate osteophyte
      resection. We present an alternative subscapularis preserving technique that is
      performed through the deltopectoral interval and allows complete osteophyte
      excision and accurate humeral head sizing. This technique requires modified
      instrumentation and is facilitated by the use of an adaptable prosthesis with
      dual eccentricity. Case examples using this technique are presented.

PMID- 24328590
TI  - Comparison of outcomes using anatomic and reverse total shoulder arthroplasty.
AB  - Worldwide, the usage of both anatomic total shoulder arthroplasty (aTSA) and
      reverse total shoulder arthro- plasty (rTSA) has increased significantly due, in
      part, to the predictability of acceptable outcomes achieved with each prosthesis
      type. This study quantifies outcomes using five different metrics and compares
      results using one platform total shoulder arthroplasty system that utilizes the
      same humeral component and instrumentation to perform both aTSA or rTSA. METHODS:
      200 patients were treated by two orthopaedic surgeons using either aTSA or rTSA.
      73 patients received aTSA for treatment of osteoarthritis (OA), and 127 patients
      received rTSA for treatment of rotator cuff tear arthro- plasty (CTA). Each was
      scored preoperatively, and at latest follow-up using the SST, UCLA, ASES,
      Constant, and SPADI metrics, motion was also quantified. The average follow-up
      for all patients was 31.4 +/- 9.7 months. RESULTS: All patients demonstrated
      significant improvements in pain and function following treatment of OA with aTSA
      and treatment of CTA with rTSA. No instances of instability or glenoid loosening
      were reported in either cohort; one instance of infection occurred in the rTSA
      cohort. aTSA was associated with significantly higher pre- and postoperative
      outcome scores and significantly larger pre- and postoperative range of motion
      than rTSA. However, rTSA was demonstrated to be significantly more effective at
      improving outcome scores, active forward flexion, and strength than was aTSA.
      DISCUSSION AND CONCLUSIONS: Significant improvements in outcome scores were
      observed for both aTSA and rTSA using one platform shoulder system at a mean
      follow-up of 31.4 months. Significant differences were observed between
      prosthesis type and between scoring metrics, particularly between the Constant
      and ASES scoring metrics. Additional and longer term follow-up is required to
      confirm these observed differences.

PMID- 24328591
TI  - The role of subscapularis repair in reverse total shoulder arthroplasty.
AB  - BACKGROUND: Controversy surrounds the role of the sub- scapularis (SSC) in
      reverse shoulder arthroplasty (rTSA) and the need for repair, if possible, at the
      conclusion of the procedure. QUESTIONS AND PURPOSE: Some investigators have
      concluded that an intact SSC is critical for stability; others have found no such
      correlation. What factors should be part of the decision-making matrix on SSC
      management for surgeons considering rTSA? FINDINGS: The data on management of the
      SSC in rTSA support a design-based approach. Researchers have shown that the SSC
      is critical to stability when the surgeon uses an implant with a medialized
      humeral component and medialized glenoid component. However, lateralized designs
      allow for more stability from horizontal deltoid compression and may not require
      repair of the SSC. In addition, SSC repair has been shown to increase the
      workload of the residual posterior rotator cuff and the deltoid in rTSA, both of
      which may have negative consequences on overall function. Lateralization from the
      glenoid component increases deltoid work, whereas lateralization from the humeral
      component maintains deltoid efficiency while improving stability. CONCLUSIONS:
      The need for SSC repair in rTSA can vary based on the implant selected. Humeral
      and glenoid offset influence the stability and kinematics of rTSA.

PMID- 24328592
TI  - Is the use of preoperative breast MRI resulting in more invasive breast cancer
      surgery?

PMID- 24328594
TI  - A journey through breast cancer research. Interview by Hannah Branch.
AB  - Fernando Schmitt speaks to Hannah Branch, Commissioning Editor Professor Fernando
      Schmitt obtained his medical degree at the University of Santa Maria (Brazil) and
      spent his pathology residency at the Medical Faculty of Botucatu (Sao Paolo,
      Brazil). In addition, he completed a Clinical Cytology fellowship at Karolinska
      Medical Hospital (Stockholm, Sweden). In 1993, Professor Schmitt relocated to
      Portugal and established a breast pathology research group in addition to a fine
      needle aspiration service at the Institute of Pathology and Immunology of
      University of Porto (Portugal). He was previously Professor of Pathology at the
      University of Porto, in addition to the Medical Director of the Unit of Pathology
      at the Institute of Pathology and Immunology of University of Porto. He has
      recently moved to the University of Toronto (Canada) to act as Full Professor of
      Pathology. He is a member of 12 national and international societies and has been
      an author of over 370 manuscripts published in peer-reviewed journals. Professor
      Schmitt kindly serves as an Editorial Board member for several journals,
      including Women's Health. 

PMID- 24328595
TI  - Women's health research in the last four decades. Interview by Natasha Leeson.
AB  - Gerson Weiss speaks to Natasha Leeson, Assistant Commissioning Editor Gerson
      Weiss obtained his MD degree from New York University (NY, USA). After an
      internship in internal medicine at Baltimore City Hospital (MD, USA), he
      completed residency in obstetrics and gynecology at New York University. Further
      training in reproductive endocrinology was obtained as a postdoctoral research
      fellow in physiology at the University of Pittsburgh (PA, USA), in the laboratory
      of Dr Ernst Knobil. Following this fellowship, Dr Weiss returned to New York
      University where he ultimately became Professor of Obstetrics and Gynecology,
      Professor of Pharmacology and Director of the Division of Reproductive
      Endocrinology and Infertility. In 1986, he became Professor and Chair of the
      Department of Obstetrics and Gynecology at New Jersey Medical School (NJ, USA).
      Dr Weiss is the author of more than 274 scientific articles. His research has
      been continuously funded since 1975 by grants from the NIH, the United Cerebral
      Palsy Foundation and the Andrew W Mellon Foundation. He has served as a member of
      the Division of Reproductive Endocrinology of the American Board of Obstetrics
      and Gynecology, a member of the Reproductive Biology Study Section of the NIH, a
      member of the Residency Review Committee for Obstetrics and Gynecology of the
      Accreditation Council for Graduate Medical Education. He has served as the
      President of the New York Obstetrical Society, the New York Gynecologic Society,
      the Council of University Chairs of Obstetrics and Gynecology, and the American
      Board of Obstetrics and Gynecology. He was the Chairman of the Committee on
      Gynecologic Practices for the American College of Obstetricians and Gynecologists
      and Chairman of American Board of Obstetrics and Gynecology. He was a member of
      the Executive Committee of the American Board of Medical Specialties. Dr Weiss is
      a past President of the Society for Gynecologic Investigation. He currently
      serves on the NIH's Advisory Committee on Research on Women's Health. Dr Weiss
      conducts an active clinical practice both in gynecology and reproductive
      endocrinology and infertility at his institution. 

PMID- 24328596
TI  - Misoprostol vaginal insert for induction of labor: a delivery system with
      accurate dosing and rapid discontinuation.
AB  - Labor induction and cervical ripening are widely utilized and new methods are
      constantly being investigated. Prostaglandins have been shown to be effective
      labor induction agents and, in particular, were compared with other prostaglandin
      preparations; vaginal misoprostol used off-label was associated with reduced
      failure to achieve vaginal delivery. The challenge is to provide this medication
      with the correct dosing for this indication and with the ability to discontinue
      the medication if needed, all while ensuring essential maternal and neonatal
      safety. The misoprostol vaginal insert initiates cervical ripening using a
      delivery system that controls misoprostol release and can be rapidly removed.
      This article reviews the development, safety and efficacy of the misoprostol
      vaginal insert for induction of labor and cervical ripening, and will focus on
      vaginally administered prostaglandins. 

PMID- 24328597
TI  - Effects of an ethinyl estradiol/gestodene transdermal contraceptive patch on the
      endometrium: a single-center, uncontrolled study.
AB  - AIM: This study aims to investigate the effect of a transdermal contraceptive
      patch containing ethinyl estradiol and gestodene on endometrial proliferation
      over 1 year. MATERIALS & METHODS: In this open-label, uncontrolled, Phase IIb
      study, women (aged 18-35 years) used the patch for 13 cycles of 28 days. The
      primary variable was histologic endometrial effects at cycle 13. Secondary
      objectives included contraceptive efficacy and safety. RESULTS: Overall, 89 women
      were treated. At all visits, endometrial biopsies were devoid of any
      abnormalities. One woman became pregnant. The patch was well tolerated, with no
      safety concerns. CONCLUSION: The ethinyl estradiol and gestodene patch had an
      endometrial effect consistent with suppression of endometrial proliferation in
      most patients. No endometrial abnormalities or other concerns were reported;
      compliance was good.

PMID- 24328599
TI  - A review of osteoporosis management in younger premenopausal women.
AB  - The purpose of this review is to describe the available evidence for osteoporosis
      treatments in young and premenopausal women. A review of articles evaluating the
      treatment or prevention of osteoporosis in young (age less than 50 years) or
      premenopausal women was conducted. Several trials evaluating the treatment of
      anorexia nervosa and use of hormone therapy in those women, the use of
      bisphosphonates in women undergoing chemotherapy for breast cancer and the use of
      bisphosphonates, teriparatide and vitamin D in women with glucocorticoid-induced
      osteoporosis are described. Limited data were found to support the treatment of
      osteoporosis in women with idiopathic osteoporosis or cystic fibrosis, or after
      kidney transplant. The evidence for treatment of osteoporosis in premenopausal
      women is not nearly as robust as that for postmenopausal osteoporosis. Although
      fracture risk in the premenopausal population is low, women with secondary
      osteoporosis may benefit from treatment with various agents, depending upon the
      condition. 

PMID- 24328600
TI  - Treating cardiac disease in pregnancy.
AB  - Maternal cardiac disease is a very significant cause of both maternal morbidity
      and mortality in westernized countries. An effective treatment program must
      tackle all of the contributing components, including those due to public health
      issues, poorly coordinated healthcare systems and inadequate medical education.
      Even with optimal care, many of these patients remain at high risk. In this
      setting, it is the role of the multidisciplinary team to counsel women regarding
      these risks and to proactively institute treatment algorithms that will optimize
      maternal and fetal outcomes. 

PMID- 24328601
TI  - Gestational diabetes mellitus and cardiovascular risk after pregnancy.
AB  - Gestational diabetes mellitus (GDM) affects many women in pregnancy and is
      enhanced by epidemic conditions of obesity, increasing age at the time of the
      first pregnancy, stressful life conditions, a sedentary lifestyle with less
      physical activity and unhealthy nutrition with highly processed, high-calorie
      food intake. GDM does not affect the mother and offspring in pregnancy alone, as
      there is compelling evidence of the long-term effects of the hyperglycemic state
      in pregnancy postpartum. Type 2 diabetes mellitus, cardiovascular disease and
      metabolic syndrome are more common in GDM women, and even the offspring of GDM
      women are reported to have higher obesity rates and a higher risk for
      noncommunicable diseases. Early prevention of risk factors seems to be key to
      overcoming the vicious cycle of cardiometabolic disease onset. 

PMID- 24328598
TI  - Targeted therapy in uterine serous carcinoma: an aggressive variant of
      endometrial cancer.
AB  - Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial
      cancer. Although it only represents less than 10% of all cases, it accounts for a
      disproportionate number of deaths from endometrial cancer. Comprehensive surgical
      staging followed by carboplatin and paclitaxel chemotherapy represents the
      mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit
      in USC. Recent whole-exome sequencing studies have demonstrated gain of function
      of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and
      cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results
      emphasize the relevance of these novel therapeutic targets for biologic therapy
      of chemotherapy-resistant recurrent USC. 

PMID- 24328602
TI  - Ultraviolet B irradiation induces skin accumulation of plasmacytoid dendritic
      cells: a possible role for chemerin.
AB  - Photosensitivity represents a common feature for most forms of lupus
      erythematosus (LE) including cutaneous LE. Skin inflammatory infiltrates in
      response to ultraviolet (UV) exposure are closely involved in the development of
      skin lesions of LE patients. Skin-infiltrating plasmacytoid dendritic cells
      (pDCs), considered as a hallmark of cutaneous LE, contribute to its pathogenesis
      via the production of type I interferons (IFNs). Chemerin, a recently identified
      chemoattractant for pDCs through its functional receptor chemR23, was found to be
      elevated in skin lesions of LE patients. The aim of this study was to investigate
      the effect of UVB irradiation on skin pDC recruitment and chemerin expression. We
      found that UVB irradiation induced a rapid but transient influx of pDCs as well
      as a persistent infiltration of neutrophils and macrophages in the mouse skin.
      The mRNA expression levels of IRF-7, IFN-alpha and chemR23 were increased in UVB
      irradiated skin. Furthermore, UVB irradiation up-regulated skin chemerin
      production and pDC accumulation in parallel, both of which reached their peaks
      simultaneously (24 h post-irradiation). Dermal fibroblasts seemed to be the major
      source of chemerin as evidenced by significantly increased chemerin secretion by
      UVB-irradiated dermal fibroblasts. More importantly, LE-prone MRL/lpr mouse
      exhibited greatly increased skin pDC accumulation and chemerin production in
      response to UVB irradiation, indicating their contributions to increased
      susceptibility of photosensitivity in the MRL/lpr mouse. Thus, our findings
      demonstrated that elevated chemerin expression positively correlates with pDC
      accumulation in UVB-irradiated skin, suggesting a role of chemerin in mediating
      skin recruitment of pDCs in response to UVB exposure.

PMID- 24328604
TI  - Ethnic variation of gastroschisis and omphalocele in the United States of
      America.
AB  - OBJECTIVE: Gastroschisis and omphalocele are the most common fetal abdominal wall
      defects (AWDs). Ethnic factors have been implicated in the incidence data from
      some states in the United States. Our aim was to examine ethnic variation in the
      prevalence of gastroschisis and omphalocele in the US live birth population
      between 2006 and 2010. METHODS: AWDs were identified through gastroschisis and
      omphalocele checkboxes from publicly available US Natality data (2006 to 2010).
      Ethnicity was evaluated by individual category using National Center for Health
      Statistics (NCHS) definitions. Adjusted multinomial logistic regression (SPSS
      v.19) was used to generate odds ratios (OR) in order to quantify the disparities.
      RESULTS: In the US, 7867 live births were identified with AWD. All ethnic groups
      showed a significantly higher OR when compared with women of East/South Asian
      descent, which experienced the lowest prevalence. Women of indigenous ethnicity
      had the highest individual OR while their adjusted OR remained greater than 4.0.
      CONCLUSIONS: Women of indigenous origin from North America and the Pacific had
      the highest rates of AWD. Within this group, women of Hawaiian descent had the
      highest point estimate of AWD when compared with other ethnic groups, though not
      significant.

PMID- 24328603
TI  - Development, characterization and in vivo localization study of topical 5
      fluorouracil gels: a comparative study with conventional formulation.
AB  - 5-Fluorouracil (5-FU) is one of the most effective antineoplastic agents used for
      the treatment of skin cancers and actinic keratosis (AK). Currently commercial
      formulation for topical 5-FU administration is available in the form of solution
      or cream. Commercial topical formulations are associated with the limitation of
      very short retention time at the administration site resulting in very poor skin
      permeation and deposition of drug. In the present study attempt was made for the
      preparation, optimization and characterization of bioadhesive gel formulations
      for localized delivery of 5-FU. Four bioadhesive gel formers, Carbopol 934,
      Carbopol 980, Methylcellulose (MC) and Poloxamer 188 were selected for the
      preparation of 5-FU bioadhesive gel formulations. The formulations were
      characterized for characteristic parameters including bioadhesive strength, skin
      deposition and interaction study. Carbopol 934 based bioadhesive gel formulation
      at the concentration of 1.5% w/w showed the best physicochemical properties such
      as viscosity (2670+/-12.2 cP), which was similar to the value obtained with the
      marketed cream (2870+/-14.4 cP), highest skin deposition (1290+/-56.4MUg) and
      bioadhesive strength (18.62 gf). Cutaneous irritation of optimized bioadhesive
      gel formulations was also tested using the Draize test and only very slight
      erythema and no oedema was observed. In comparison, marketed formulation showed
      well defined erythema along with oedema formation. The result of the present
      study demonstrated that formulation of Carbopol 934 based 5-FU bioadhesive gel is
      a better alternative to the traditional cream base for enhanced topical delivery
      of 5-FU. The developed formulation will have the ease of application, better skin
      deposition and sustained release characteristic with reduced skin toxicity. 

PMID- 24328605
TI  - Migration, integration and maturation of photoreceptor precursors following
      transplantation in the mouse retina.
AB  - Retinal degeneration leading to loss of photoreceptors is a major cause of
      untreatable blindness. Recent research has yielded definitive evidence for
      restoration of vision following the transplantation of rod photoreceptors in
      murine models of blindness, while advances in stem cell biology have enabled the
      generation of transplantable photoreceptors from embryonic stem cells.
      Importantly, the amount of visual function restored is dependent upon the number
      of photoreceptors that migrate correctly into the recipient retina. The
      developmental stage of the donor cells is important for their ability to migrate;
      they must be immature photoreceptor precursors. Little is known about how and
      when donor cell migration, integration, and maturation occurs. Here, we have
      performed a comprehensive histological analysis of the 6-week period following
      rod transplantation in mice. Donor cells migrate predominately as single entities
      during the first week undergoing a stereotyped sequence of morphological changes
      in their translocation from the site of transplantation, through the
      interphotoreceptor matrix and into the recipient retina. This includes initial
      polarization toward the outer nuclear layer (ONL), followed by formation of an
      apical attachment and rudimentary segment during migration into the ONL.
      Strikingly, acquisition of a nuclear architecture typical of mature rods was
      accelerated compared with normal development and a feature of migrating cells.
      Once within the ONL, precursors formed synaptic-like structures and outer
      segments in accordance with normal maturation. The restoration of visual function
      mediated by transplanted photoreceptors correlated with the later expression of
      rod alpha-transducin, achieving maximal function by 5 weeks. 

PMID- 24328606
TI  - Protein kinase inhibitors in renal cell carcinoma.
AB  - INTRODUCTION: Metastatic Renal Cell Carcinoma (mRCC) was historically treated
      with cytokine therapy with a poor outcome. In the last decade, new therapies
      targeting vascular endothelial growth factor (VEGF) or the mammalian target of
      rapamycin (m-TOR) pathways demonstrated efficacy in mRCC. Protein kinase
      inhibitors as well as monoclonal antibodies targeting these pathways have become
      the standard treatment of renal cell carcinoma (RCC) in the first-line setting
      and beyond. AREAS COVERED: This review describes the various Phase III trials
      concerning protein kinase inhibitors including anti-angiogenic tyrosine kinase
      inhibitors (TKIs) and m-TOR serine/threonine kinase inhibitors, which have
      demonstrated a benefit in the treatment of mRCC. It focuses on efficacy, safety
      and management. EXPERT OPINION: VEGF TKI and m-TOR inhibitors have significantly
      improved the outcome of mRCC and offer a gain in survival by sequential
      treatments for the majority of patients. But they induce a particular toxicity
      profile. An adequate management of each drug and its sequence in treatment is
      essential to optimise the outcome and preserve the quality of life (QoL) of
      patients with mRCC. In forthcoming years, pending results should indicate whether
      VEGF TKI are of interest in an adjuvant setting and if new drugs targeting will
      challenge the current standard guidelines in the metastatic setting.

PMID- 24328607
TI  - Outcome of Er,Cr:YSGG laser-assisted treatment of teeth with apical
      periodontitis: a blind randomized clinical trial.
AB  - OBJECTIVE: As clinical studies conducted to explore the safety and efficacy of
      new procedures are considered an important focus in endodontic research, the aim
      of this controlled clinical study was to compare a laser-assisted endodontic
      treatment using an erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG)
      laser and radial firing tips (RFT) versus the conventional use of 3% sodium
      hypochlorite and interim calcium hydroxide paste, in teeth with chronic apical
      periodontitis. METHODS: Forty-three single-rooted and premolar teeth were
      randomly assigned. In group 1, teeth were prepared and irrigated with 3% sodium
      hypochlorite and calcium hydroxide inter-appointment dressing was applied; in
      group 2 teeth were prepared with saline solution and irradiated with Er,Cr:YSGG
      laser using RFT2 (140 MUs, 37.5 mJ, 20 Hz) and RFT3 (140 MUs, 62.5 mJ, 20 Hz) at
      the first and second appointments, respectively, four times each, moving at 2
      mm/sec(-1) from apical to coronal. The primary outcome measure was change in
      apical bone density at 12 months, using the periapical index (PAI) for blind
      radiographic assessment. RESULTS: Thirty teeth were examined and subjected to
      statistical analysis, 12 in the control group and 18 in the test group. There
      were two treatment failures in the control group that were not included for
      analysis; both groups exhibited statistically significant decreases in PAI
      scores. CONCLUSIONS: The present findings suggest that for single-rooted and
      premolar teeth, this laser-assisted protocol can achieve predictable endodontic
      outcomes, comparable to conventional strategies in 1 year of follow-up.

PMID- 24328608
TI  - Cutaneous sporotrichosis treated with photodynamic therapy: an in vitro and in
      vivo study.
AB  - BACKGROUND: Sporotrichosis is a fungal infection caused by Sporothrix schenckii
      complex, usually restricted to the skin, subcutaneous cellular tissue, and
      adjacent lymphatic vessels. Antimicrobial photodynamic therapy (aPDT) could be a
      good alternative to manage localized, superficial infections. CASE REPORT: A 65
      year-old African woman was diagnosed with a fixed cutaneous sporotrichosis on her
      left arm, treated with itraconazol and oral terbinafine with partial improvement.
      Topical 16% methyl aminolevulinate (MAL, Metvix((r)))-PDT was used without
      success. METHODS: An in vitro photoinactivation test with the isolated
      microorganism revealed phenothiazinium salts to be more effective than MAL.
      CONCLUSIONS: PDT with intralesional 1% methylene blue (MB) in combination with
      intermittent low doses of itraconazole obtained complete microbiological and
      clinical response.

PMID- 24328609
TI  - Transmission of Er:YAG laser through different dental ceramics.
AB  - OBJECTIVE: The aim of this study was to determine the erbium-doped yttrium
      aluminum garnet (Er:YAG) laser transmission ratio through different dental
      ceramics with different thicknesses. BACKGROUND DATA: Laser debonding procedure
      of adhesively luted all-ceramic restorations is based on the transmission of
      laser energy through the ceramic and the ablation of resin cement, because of the
      transmitted laser energy. METHODS: Five different dental ceramics were evaluated
      in this study: sintered zirconium-oxide core ceramic, monolithic zirconium-oxide
      ceramic, feldspathic ceramic, leucite-reinforced glass ceramic, and lithium
      disilicate-reinforced glass ceramic. Two ceramic discs with different thicknesses
      (0.5 and 1 mm) were fabricated for each group. Ceramic discs were placed between
      the sensor membrane of the laser power meter and the tip of the contact handpiece
      of an Er:YAG laser device with the aid of a custom- made acrylic holder. The
      transmission ratio of Er:YAG laser energy (500 mJ, 2 Hz, 1 W, 1000 MUs) through
      different ceramic discs was measured with the power meter. Ten measurements were
      made for each group and the results were analyzed with two way analysis of
      variance (ANOVA) and Tukey honestly significant difference (HSD) tests. RESULTS:
      The highest transmission ratio was determined for lithium disilicate-reinforced
      ceramic with 0.5 mm thickness (88%) and the lowest was determined for feldspathic
      ceramic with 1 mm thickness (44%). The differences among the different ceramics
      and between the different thicknesses were significant (p<0.05). CONCLUSIONS:
      Ceramic type and thickness should be taken into consideration to adjust the laser
      irradiation parameters during laser debonding of adhesively luted all-ceramic
      restorations.

PMID- 24328610
TI  - A feasibility study on femtosecond laser thrombolysis.
AB  - OBJECTIVE: In this feasibility study, we investigate possible femtosecond laser
      thrombolysis. BACKGROUND DATA: Because of low pulse energies, femtosecond laser
      surgery inherently minimizes side effects on the surrounding tissue. Moreover,
      current femtosecond laser sources as well as fiber technology allow consideration
      of catheter-based treatments. METHODS: Two femtosecond laser systems (lambda=800
      nm, lambda=1030 nm) along with a three dimensional (3D) scanner system (NA ~0.1)
      were used in this study. In vitro experiments were performed on porcine thrombi
      and blood vessels. Ablation thresholds were determined in air, by determining the
      pulse energy at which single shot ablation was visible under the optical
      microscope. Ablation rates were determined in physiological saline. Additionally,
      ablation of thrombi and blood vessels was monitored by means of a fiber
      spectrometer. RESULTS: Depending upon the scan velocity, typical ablation rates
      for thrombi were ~0.04 mm(3)/sec. Ablation thresholds of thrombi and blood
      vessels differ by factors of 3 and 1.5 at laser wavelengths of 800 and 1030 nm,
      respectively. At a distance of 5 mm above the surface, second harmonic generation
      was observed in blood vessels, but not within thrombi. CONCLUSIONS: The results
      show that a typical thrombus volume can be destroyed within a reasonable time
      frame. Because of the higher threshold difference of thrombi and blood vessels,
      the use of a laser wavelength of 800 nm is preferable. Furthermore, the detection
      of the second harmonic could provide a feedback mechanism to protect the vascular
      wall from mechanical and laser damage.

PMID- 24328612
TI  - A personal reflection on the history of population-based research with sexual
      minority youths.

PMID- 24328611
TI  - Smoking initiation associated with specific periods in the life course from birth
      to young adulthood: data from the National Longitudinal Survey of Youth 1997.
AB  - OBJECTIVES: Guided by the life-course perspective, we examined whether there were
      subgroups with different likelihood curves of smoking onset associated with
      specific developmental periods. METHODS: Using 12 waves of panel data from 4088
      participants in the National Longitudinal Survey of Youth 1997, we detected
      subgroups with distinctive risk patterns by employing developmental trajectory
      modeling analysis. RESULTS: From birth to age 29 years, 72% of female and 74% of
      US males initiated smoking. We detected 4 exclusive groups with distinctive risk
      patterns for both genders: the Pre-Teen Risk Group initiated smoking by age 12
      years, the Teenage Risk Group initiated smoking by age 18 years, the Young Adult
      Risk Group initiated smoking by age 25 years, and the Low Risk Group experienced
      little or no risk over time. Groups differed on several etiological and outcome
      variables. CONCLUSIONS: The process of smoking initiation from birth to young
      adulthood is nonhomogeneous, with distinct subgroups whose risk of smoking onset
      is linked to specific stages in the life course.

PMID- 24328613
TI  - Using organizational network analysis to plan cancer screening programs for
      vulnerable populations.
AB  - OBJECTIVES: We examined relationships among organizations in a cancer screening
      network to inform the development of interventions to improve cancer screening
      for South Asians living in the Peel region of Ontario. METHODS: From April to
      July 2012, we surveyed decision-makers, program managers, and program staff in 22
      organizations in the South Asian cancer screening network in the Peel region. We
      used a network analytic approach to evaluate density (range = 0%-100%, number of
      ties among organizations in the network expressed as a percentage of all possible
      ties), centralization (range = 0-1, the extent of variability in centrality), and
      node characteristics for the communication, collaboration, and referral networks.
      RESULTS: Density was similar across communication (15%), collaboration (17%), and
      referral (19%) networks. Centralization was greater in the collaboration network
      (0.30) than the communication network (0.24), and degree centralization was
      greater in the inbound (0.42) than the outbound (0.37) referral network. Diverse
      organizations were central to the networks. CONCLUSIONS: Certain organizations
      were unexpectedly important to the South Asian cancer screening network. Program
      planning was informed by identifying opportunities to strengthen linkages between
      key organizations and to leverage existing ties.

PMID- 24328615
TI  - Avoiding violent victimization among youths in urban neighborhoods: the
      importance of street efficacy.
AB  - OBJECTIVES: We investigated how street efficacy--the perceived ability to avoid
      dangerous and unsafe situations--is related to violent victimization across
      different levels of neighborhood disadvantage. METHODS: We used 2 waves of self
      report data collected between 1995 and 1999 from 1865 youths in the 9-, 12-, and
      15-year-old cohorts of the Project on Human Development in Chicago Neighborhoods
      to measure violent victimization, street efficacy, and risk factors for violent
      victimization. We also analyzed data from the 1990 US Census to measure
      categories of neighborhood concentrated disadvantage for which the cohorts of
      youths reside. We used logistic regression models to examine the association
      between street efficacy and violent victimization while we controlled for
      demographic, family and parenting, self-control, and behavioral and lifestyle
      variables. RESULTS: Logistic regression results showed that street efficacy had
      its strongest association with violent victimization in the most disadvantaged
      neighborhoods (odds ratio = 0.700; 95% confidence interval = 0.55, 0.89).
      CONCLUSIONS: Our findings support the need to teach youths ways to successfully
      navigate potentially violent situations in environments that pose moderate to
      high risks for exposure to violence.

PMID- 24328614
TI  - Exploring alcohol-use behaviors among heterosexual and sexual minority
      adolescents: intersections with sex, age, and race/ethnicity.
AB  - OBJECTIVES: We examined sexual orientation status differences in alcohol use
      among youths aged 13 to 18 years or older, and whether differences were moderated
      by sex, age, or race/ethnicity. METHODS: We pooled data from the 2005 and 2007
      Youth Risk Behavior Surveys and conducted weighted analyses, adjusting for
      complex design effects. We operationalized sexual orientation status with items
      assessing sexual orientation identity, sexual behavior, sexual attraction, or
      combinations of these. RESULTS: Compared with exclusively heterosexual youths,
      sexual-minority youths were more likely to report each of the primary study
      outcomes (i.e., lifetime and past-month alcohol use, past-month heavy episodic
      drinking, earlier onset of drinking, and more frequent past-month drinking).
      Alcohol-use disparities were larger and more robust for (1) bisexual youths than
      lesbian or gay youths, (2) girls than boys, and (3) younger than older youths.
      Few differences in outcomes were moderated by race/ethnicity. CONCLUSIONS:
      Bisexual youths, sexual-minority girls, and younger sexual-minority youths showed
      the largest alcohol-use disparities. Research is needed that focuses on
      identifying explanatory or mediating mechanisms, psychiatric or mental health
      comorbidities, and long-term consequences of early onset alcohol use,
      particularly frequent or heavy use, among sexual-minority youths.

PMID- 24328616
TI  - National and state-specific health insurance disparities for adults in same-sex
      relationships.
AB  - OBJECTIVES: We examined national and state-specific disparities in health
      insurance coverage, specifically employer-sponsored insurance (ESI) coverage, for
      adults in same-sex relationships. METHODS: We used data from the American
      Community Survey to identify adults (aged 25-64 years) in same-sex relationships
      (n = 31,947), married opposite-sex relationships (n = 3,060,711), and unmarried
      opposite-sex relationships (n = 259,147). We estimated multinomial logistic
      regression models and state-specific relative differences in ESI coverage with
      predictive margins. RESULTS: Men and women in same-sex relationships were less
      likely to have ESI than were their married counterparts in opposite-sex
      relationships. We found ESI disparities among adults in same-sex relationships in
      every region, but we found the largest ESI gaps for men in the South and for
      women in the Midwest. ESI disparities were narrower in states that had extended
      legal same-sex marriage, civil unions, and broad domestic partnerships.
      CONCLUSIONS: Men and women in same-sex relationships experience disparities in
      health insurance coverage across the country, but residing in a state that
      recognizes legal same-sex marriage, civil unions, or broad domestic partnerships
      may improve access to ESI for same-sex spouses and domestic partners.

PMID- 24328617
TI  - Military sexual trauma among US servicewomen during deployment: a qualitative
      study.
AB  - OBJECTIVES: We explored qualitatively US servicewomen's experiences with and
      perceptions of military sexual trauma (MST), reporting, and related services.
      METHODS: From May 2011 to January 2012, we conducted 22 telephone interviews with
      US servicewomen deployed overseas between 2002 and 2011. We analyzed data
      thematically with modified grounded theory methods. RESULTS: Factors identified
      as contributing to MST included deployment dynamics, military culture, and lack
      of consequences for perpetrators. Participants attributed low MST reporting to
      negative reactions and blame from peers and supervisors, concerns about
      confidentiality, and stigma. Unit cohesion was cited as both a facilitator and a
      barrier to reporting. Availability and awareness of MST services during
      deployment varied. Barriers to care seeking were similar to reporting barriers
      and included confidentiality concerns and stigma. We identified several avenues
      to address MST, including strengthening consequences for perpetrators.
      CONCLUSIONS: We identified barriers to MST reporting and services. Better
      understanding of these issues will allow policymakers to improve MST prevention
      and services.

PMID- 24328618
TI  - Envisioning an America without sexual orientation inequities in adolescent
      health.
AB  - This article explicates a vision for social change throughout multiple levels of
      society necessary to eliminate sexual orientation health disparities in youths.
      We utilized the framework of Bronfenbrenner's ecological theory of development, a
      multisystemic model of development that considers direct and indirect influences
      of multiple levels of the environment. Within this multisystem model we discuss
      societal and political influences, educational systems, neighborhoods and
      communities, romantic relationships, families, and individuals. We stress that
      continued change toward equity in the treatment of lesbian, gay, and bisexual
      youths across these levels will break down the barriers for these youths to
      achieve healthy development on par with their heterosexual peers. 

PMID- 24328620
TI  - The importance of public health agency independence: Marcellus shale gas drilling
      in Pennsylvania.
AB  - Public health often deals with inconvenient truths. These are best communicated
      and acted on when public health agencies are independent of the organizations or
      individuals for whom the truths are inconvenient. The importance of public health
      independence is exemplified by the lack of involvement of the Pennsylvania
      Department of Health in responding to health concerns about shale gas drilling.
      Pennsylvania Department of Health involvement has been forestalled by the state
      governor, who has intensely supported shale gas development. 

PMID- 24328619
TI  - Lesbian, gay, bisexual, and transgender hate crimes and suicidality among a
      population-based sample of sexual-minority adolescents in Boston.
AB  - OBJECTIVES: We examined whether past-year suicidality among sexual-minority
      adolescents was more common in neighborhoods with a higher prevalence of hate
      crimes targeting lesbian, gay, bisexual, and transgender (LGBT) individuals.
      METHODS: Participants' data came from a racially/ethnically diverse population
      based sample of 9th- through 12th-grade public school students in Boston,
      Massachusetts (n = 1292). Of these, 108 (8.36%) reported a minority sexual
      orientation. We obtained data on LGBT hate crimes involving assaults or assaults
      with battery between 2005 and 2008 from the Boston Police Department and linked
      the data to the adolescent's residential address. RESULTS: Sexual-minority youths
      residing in neighborhoods with higher rates of LGBT assault hate crimes were
      significantly more likely to report suicidal ideation (P = .013) and suicide
      attempts (P = .006), than were those residing in neighborhoods with lower LGBT
      assault hate crime rates. We observed no relationships between overall
      neighborhood-level violent and property crimes and suicidality among sexual
      minority adolescents (P > .05), providing evidence for specificity of the results
      to LGBT assault hate crimes. CONCLUSIONS: Neighborhood context (i.e., LGBT hate
      crimes) may contribute to sexual-orientation disparities in adolescent
      suicidality, highlighting potential targets for community-level suicide
      prevention programs.

PMID- 24328621
TI  - The relation between health insurance and health care disparities among adults
      with disabilities.
AB  - OBJECTIVES: We examined disparities among US adults with disabilities and the
      degree to which health insurance attenuates disparities by race, ethnicity, and
      socioeconomic status (SES). METHODS: We pooled data from the 2001-2007 Medical
      Expenditure Panel Survey on individuals with disabilities aged 18 to 64 years. We
      modeled measures of access and use as functions of predisposing, enabling, need,
      and contextual factors. We then included health insurance and examined the extent
      to which it reduced observed differences by race, ethnicity, and SES. RESULTS: We
      found evidence of disparities in access and use among adults with disabilities.
      Adjusting for health insurance reduced these disparities most consistently for
      emergency department use. Uninsured individuals experienced substantially poorer
      access across most measures, including reporting a usual source of care and
      experiencing delays in or being unable to obtain care. CONCLUSIONS: Although
      health insurance is an important enabling resource among adults with
      disabilities, its effect on reducing differences by race, ethnicity, and SES on
      health care access and use was limited. Research exploring the effects of factors
      such as patient-provider interactions is warranted.

PMID- 24328622
TI  - The lifetime effect of residential school attendance on indigenous health status.
AB  - OBJECTIVES: I examined the health impact of lifetime Indian Residential school
      (IRS) attendance and the mediating influences of socioeconomic status and
      community adversity on health outcomes in a national sample of Aboriginal peoples
      in Canada. METHODS: In an analysis of data on 13,881 Inuit, Metis, and off
      reserve First Nations or North American Indian adults responding to the
      postcensus 2006 Aboriginal Peoples Survey administered October 2006 to March
      2007, I tested the direct effect of IRS attendance on health and indirect effects
      through socioeconomic and community factors using logistic regression procedures.
      RESULTS: Negative health status was significantly more likely with IRS attendance
      than nonattendance. The direct effect of IRS attendance remained significant
      although it attenuated substantially when adjusting for demographic
      characteristics, socioeconomic status, and community-level adversities. Community
      adversity and socioeconomic factors, primarily income, employment status, and
      educational attainment mediated the effect of IRS on health. CONCLUSIONS:
      Residential school attendance is a significant health determinant in the
      Indigenous population and is adversely associated with subsequent health status
      both directly and through the effects of attendance on socioeconomic and
      community-level risks.

PMID- 24328623
TI  - Health for all: the Lesbian, Gay, Bisexual, and Transgender Older Adult Project.

PMID- 24328624
TI  - Gibb et al. respond.

PMID- 24328625
TI  - The triumph of politics over public health: states opting out of Medicaid
      expansion.

PMID- 24328627
TI  - Incorrect analyses of radiation and mesothelioma.

PMID- 24328628
TI  - Mandatory influenza vaccination for health care workers as the new standard of
      care: a matter of patient safety and nonmaleficent practice.
AB  - A growing body of literature defends the efficacy of seasonal influenza
      vaccination for health care workers in reducing the mortality of hospitalized
      patients. I review the evidence concerning influenza vaccination, concluding that
      universal vaccination of health care workers against influenza should be
      considered standard patient care and that nonvaccination represents maleficent
      care. I further argue that the ethical responsibility to ensure universal
      vaccination of staff against seasonal influenza lies not only with individual
      health care providers but with each individual health care institution. 

PMID- 24328626
TI  - Secondhand smoke exposure among young adult sexual minority bar and nightclub
      patrons.
AB  - OBJECTIVES: We compared exposure to secondhand smoke (SHS) and attitudes toward
      smoke-free bar and nightclub policies among patrons of lesbian, gay, bisexual,
      and transgender (LGBT) and non-LGBT bars and nightclubs. METHODS: We conducted
      randomized time-location sampling surveys of young adults (aged 21-30 years) in 7
      LGBT (n = 1113 patrons) and 12 non-LGBT (n = 1068 patrons) venues in Las Vegas,
      Nevada, in 2011, as part of a cross-sectional study of a social branding
      intervention to promote a tobacco-free lifestyle and environment in bars and
      nightclubs. RESULTS: Compared with non-LGBT bars and nightclubs, patrons of LGBT
      venues had 38% higher adjusted odds of having been exposed to SHS in a bar or
      nightclub in the past 7 days but were no less likely to support smoke-free
      policies and intended to go out at least as frequently if a smoke-free bar and
      nightclub law was passed. CONCLUSIONS: The policy environment in LGBT bars and
      nightclubs appears favorable for the enactment of smoke-free policies, which
      would protect patrons from SHS and promote a smoke-free social norm.

PMID- 24328629
TI  - Breaking the blue wall of silence: risk factors for experiencing police sexual
      misconduct among female offenders.
AB  - OBJECTIVES: We assessed the prevalence of and risk factors for trading sex with a
      police officer among women recruited from drug courts in St Louis, Missouri.
      METHODS: In 2005 to 2008, we recruited women into an HIV intervention study,
      which surveyed participants about multiple sociodemographic, lifestyle, and risk
      factors. Regression analyses assessed risk factors for trading sex, a form of
      police sexual misconduct (PSM). RESULTS: Of the 318 participants, 78 (25%)
      reported a lifetime history of PSM. Among women who experienced PSM, 96% had sex
      with an officer on duty, 77% had repeated exchanges, 31% reported rape by an
      officer, and 54% were offered favors by officers in exchange for sex; 87% said
      officers kept their promise. Only 51% of these respondents always used a condom
      with an officer. Multivariable models identified 4 or more arrests (adjusted odds
      ratio [AOR] = 2.8; 95% confidence interval [CI] = 1.29, 5.97), adult antisocial
      personality (AOR = 9.0; 95% CI = 2.08, 38.79), and lifetime comorbid cocaine and
      opiate use (AOR = 2.9 [1.62, 5.20]) as risk factors; employment (AOR = 0.4; 95%
      CI = 0.22, 0.77) lowered the risk of PSM. CONCLUSIONS: Community-based
      interventions are critical to reduce risk of abuse of vulnerable women by police
      officers charged with protecting communities.

PMID- 24328630
TI  - Health disparities among sexual minority youth: the value of population data.

PMID- 24328631
TI  - Influenza and seasonal patterns of hospital use by older adults in long-term care
      and community settings in Ontario, Canada.
AB  - OBJECTIVES: We compared seasonal influenza hospital use among older adults in
      long-term care (LTC) and community settings. METHODS: We used provincial
      administrative data from Ontario to identify all emergency department (ED) visits
      and hospital admissions for pneumonia and influenza among adults older than 65
      years between 2002 and 2008. We used sentinel laboratory reports to define
      influenza and summer seasons and estimated mean annual event rates and influenza
      associated rates. RESULTS: Mean annual pneumonia and influenza ED visit rates
      were higher in LTC than the community (rate ratio [RR] for influenza season =
      3.9; 95% confidence interval [CI] = 3.8, 4.0; for summer = 4.9; 95% CI = 4.8,
      5.1) but this was attenuated in influenza-associated rates (RR = 2.4; 95% CI =
      2.1, 2.8). The proportion of pneumonia and influenza ED visits attributable to
      seasonal influenza was 17% (15%-20%) in LTC and 28% (27%-29%) in the community.
      Results for hospital admissions were comparable. CONCLUSIONS: We found high rates
      of hospital use from LTC but evidence of lower impact of circulating influenza in
      the community. This differential impact of circulating influenza between the 2
      environments may result from different influenza control policies.

PMID- 24328633
TI  - Indicators of victimization and sexual orientation among adolescents: analyses
      from Youth Risk Behavior Surveys.
AB  - OBJECTIVES: We used nuanced measures of sexual minority status to examine
      disparities in victimization and their variations by gender, age, and
      race/ethnicity. METHODS: We conducted multivariate analyses of pooled data from
      the 2005 and 2007 Youth Risk Behavior Surveys. RESULTS: Although all sexual
      minorities reported more fighting, skipping school because they felt unsafe, and
      having property stolen or damaged at school than did heterosexuals, rates were
      highest among youths who identified as bisexual or who reported both male and
      female sexual partners. Gender differences among sexual minorities appeared to be
      concentrated among bisexuals and respondents who reported sexual partners of both
      genders. Sexual minority youths reported more fighting than heterosexual youths,
      especially at younger ages, and more nonphysical school victimization that
      persisted through adolescence. White and Hispanic sexual minority youths reported
      more indicators of victimization than did heterosexuals; we found few sexual
      minority differences among African American and Asian American youths.
      CONCLUSIONS: Victimization carries health consequences, and sexual minorities are
      at increased risk. Surveys should include measures that allow tracking of
      disparities in victimization by sexual minority status.

PMID- 24328632
TI  - Sexual orientation disparities in cancer-related risk behaviors of tobacco,
      alcohol, sexual behaviors, and diet and physical activity: pooled Youth Risk
      Behavior Surveys.
AB  - OBJECTIVES: We examined sexual orientation disparities in cancer-related risk
      behaviors among adolescents. METHODS: We pooled data from the 2005 and 2007 Youth
      Risk Behavior Surveys. We classified youths with any same-sex orientation as
      sexual minority and the remainder as heterosexual. We compared the groups on risk
      behaviors and stratified by gender, age (< 15 years and > 14 years), and
      race/ethnicity. RESULTS: Sexual minorities (7.6% of the sample) reported more
      risk behaviors than heterosexuals for all 12 behaviors (mean = 5.3 vs 3.8; P <
      .001) and for each risk behavior: odds ratios (ORs) ranged from 1.3 (95%
      confidence interval [CI] = 1.2, 1.4) to 4.0 (95% CI = 3.6, 4.7), except for a
      diet low in fruit and vegetables (OR = 0.7; 95% CI = 0.5, 0.8). We found sexual
      orientation disparities in analyses by gender, followed by age, and then
      race/ethnicity; they persisted in analyses by gender, age, and race/ethnicity,
      although findings were nuanced. CONCLUSIONS: Data on cancer risk, morbidity, and
      mortality by sexual orientation are needed to track the potential but unknown
      burden of cancer among sexual minorities.

PMID- 24328634
TI  - Protective school climates and reduced risk for suicide ideation in sexual
      minority youths.
AB  - OBJECTIVES: We examined whether sexual minority students living in states and
      cities with more protective school climates were at lower risk of suicidal
      thoughts, plans, and attempts. METHODS: Data on sexual orientation and past-year
      suicidal thoughts, plans, and attempts were from the pooled 2005 and 2007 Youth
      Risk Behavior Surveillance Surveys from 8 states and cities. We derived data on
      school climates that protected sexual minority students (e.g., percentage of
      schools with safe spaces and Gay-Straight Alliances) from the 2010 School Health
      Profile Survey, compiled by the Centers for Disease Control and Prevention.
      RESULTS: Lesbian, gay, and bisexual students living in states and cities with
      more protective school climates reported fewer past-year suicidal thoughts than
      those living in states and cities with less protective climates (lesbians and
      gays: odds ratio [OR] = 0.68; 95% confidence interval [CI] = 0.47, 0.99;
      bisexuals: OR = 0.81; 95% CI = 0.66, 0.99). Results were robust to adjustment for
      potential state-level confounders. Sexual orientation disparities in suicidal
      thoughts were nearly eliminated in states and cities with the most protective
      school climates. CONCLUSIONS: School climates that protect sexual minority
      students may reduce their risk of suicidal thoughts.

PMID- 24328635
TI  - Dental care coverage and use: modeling limitations and opportunities.
AB  - OBJECTIVES: We examined why older US adults without dental care coverage and use
      would have lower use rates if offered coverage than do those who currently have
      coverage. METHODS: We used data from the 2008 Health and Retirement Study to
      estimate a multinomial logistic model to analyze the influence of personal
      characteristics in the grouping of older US adults into those with and those
      without dental care coverage and dental care use. RESULTS: Compared with persons
      with no coverage and no dental care use, users of dental care with coverage were
      more likely to be younger, female, wealthier, college graduates, married, in
      excellent or very good health, and not missing all their permanent teeth.
      CONCLUSIONS: Providing dental care coverage to uninsured older US adults without
      use will not necessarily result in use rates similar to those with prior coverage
      and use. We have offered a model using modifiable factors that may help policy
      planners facilitate programs to increase dental care coverage uptake and use.

PMID- 24328636
TI  - Mental illness and violence: lessons from the evidence.
AB  - The debate about addressing mental illness and violence often ignores key facts.
      Many people experience mental illnesses, so having had a diagnosed illness is not
      a very specific predictor of violent behavior. This means that many proposed
      policy approaches, from expanded screening to more institutionalization, are
      unlikely to be effective. Expanded access to effective treatments, although
      desirable, will have only modest impacts on violence rates. Most people with
      mental health problems do not commit violent acts, and most violent acts are not
      committed by people with diagnosed mental disorders. 

PMID- 24328637
TI  - Cigarette smoking and mental illness: a study of nicotine withdrawal.
AB  - OBJECTIVES: We compared prevalence, severity, and specific symptom profiles for
      nicotine withdrawal across categories of mental illness. We also examined the
      influence of nicotine withdrawal on efforts to quit smoking among those with
      mental illness. METHODS: We analyzed data from 2 sources: wave 1 of the National
      Epidemiologic Survey on Alcohol and Related Conditions, limiting the sample to
      current smokers (2001-2002; n = 9913); and a 2-wave cohort telephone survey of a
      national sample of adult smokers (2004-2006; n = 751). RESULTS: Mental illness
      was associated with a substantially greater likelihood of nicotine withdrawal
      syndrome; approximately 44% of nicotine withdrawal syndrome diagnoses were
      attributable to mental illness. Symptom profiles were highly comparable between
      mental illness categories, although anxiety-related symptoms were better markers
      of withdrawal for those with an internalizing disorder. Smokers with mental
      illness were motivated to quit but were less likely to be successful in their
      quit attempts, and both dependence and withdrawal independently accounted for
      this lower likelihood of success. CONCLUSIONS: Nicotine withdrawal may be a
      particularly important target for intervention among those with mental illness
      who smoke cigarettes.

PMID- 24328638
TI  - The impact of smoke-free laws on asthma discharges: a multistate analysis.
AB  - OBJECTIVES: This is the first, to my knowledge, multistate, county-level analysis
      of Healthcare Cost and Utilization Project state inpatient data to examine the
      relationship between smoke-free laws and asthma discharges. METHODS: I used
      treatment and control groups to examine the effects of state and county or city
      smoke-free laws separately and together (2002-2009). I compared quarterly county
      level discharge rates before and after the implementation of 12 state smoke-free
      laws, accounting for counties with preexisting county or city smoke-free laws and
      using the data from 5 states without state smoke-free laws as a control group. I
      used difference-in-differences models, controlling for year and state fixed
      effects, state cigarette taxes, seasonality, and numerous county-level factors.
      RESULTS: I observed statistically significant reductions in asthma discharges
      after the implementation of county smoke-free laws but no statistically
      significant effect of state laws besides the effect of county laws or of state
      laws alone. There was also no statistically significant effect of any smoke-free
      law on appendicitis discharges. CONCLUSIONS: It may be unwise to pursue state
      smoke-free laws where they have yet to pass; rather, efforts might be better
      focused at the local level, where there is evidence of a significant impact.

PMID- 24328639
TI  - Analyzing whether countries are equally efficient at improving longevity for men
      and women.
AB  - OBJECTIVES: We examined the efficiency of country-specific health care spending
      in improving life expectancies for men and women. METHODS: We estimated
      efficiencies of health care spending for 27 Organisation for Economic Co
      operation and Development (OECD) countries during the period 1991 to 2007 using
      multivariable regression models, including country fixed-effects and controlling
      for time-varying levels of national social expenditures, economic development,
      and health behaviors. RESULTS: Findings indicated robust differences in health
      spending efficiency. A 1% annual increase in health expenditures was associated
      with percent changes in life expectancy ranging from 0.020 in the United States
      (95% confidence interval [CI] = 0.008, 0.032) to 0.121 in Germany (95% CI =
      0.099, 0.143). Health-spending increases were associated with greater life
      expectancy improvements for men than for women in nearly every OECD country.
      CONCLUSIONS: This is the first study to our knowledge to estimate the effect of
      country-specific health expenditures on life expectancies of men and women.
      Future work understanding the determinants of these differences has the potential
      to improve the overall efficiency and equity of national health systems.

PMID- 24328640
TI  - Identifying sexual orientation health disparities in adolescents: analysis of
      pooled data from the Youth Risk Behavior Survey, 2005 and 2007.
AB  - We studied sexual orientation disparities in health outcomes among US adolescents
      by pooling multiple Youth Risk Behavior Survey (YRBS) data sets from 2005 and
      2007 for 14 jurisdictions. Here we describe the methodology for pooling and
      analyzing these data sets. Sexual orientation-related items assessed sexual
      orientation identity, gender of sexual contacts, sexual attractions, and
      harassment regarding sexual orientation. Wording of items varied across
      jurisdictions, so we created parallel variables and composite sexual minority
      variables. We used a variety of statistical approaches to address issues with the
      analysis of pooled data and to meet the aims of individual articles, which
      focused on a range of health outcomes and behaviors related to cancer, substance
      use, sexual health, mental health, violence, and injury. 

PMID- 24328641
TI  - A syndemic of psychosocial health disparities and associations with risk for
      attempting suicide among young sexual minority men.
AB  - OBJECTIVES: We examined a syndemic of psychosocial health issues among young men
      who have sex with men (MSM), with men and women (MSMW), and with women (MSW). We
      examined hypothesized drivers of syndemic production and effects on suicide
      attempts. METHODS: Using a pooled data set of 2005 and 2007 Youth Risk Behavior
      Surveys from 11 jurisdictions, we used structural equation modeling to model a
      latent syndemic factor of depression symptoms, substance use, risky sex, and
      intimate partner violence. Multigroup models examined relations between
      victimization and bullying experiences, syndemic health issues, and serious
      suicide attempts. RESULTS: We found experiences of victimization to increase
      syndemic burden among all male youths, especially MSMW and MSM compared with MSW
      (variance explained = 44%, 38%, and 10%, respectively). The syndemic factor was
      shown to increase the odds of reporting a serious suicide attempt, particularly
      for MSM (odds ratio [OR] = 5.75; 95% confidence interval [CI] = 1.36, 24.39; P <
      .001) and MSMW (OR = 5.08; 95% CI = 2.14, 12.28; P < .001) compared with MSW (OR
      = 3.47; 95% CI = 2.50, 4.83; P < .001). CONCLUSIONS: Interventions addressing
      multiple psychosocial health outcomes should be developed and tested to better
      meet the needs of young MSM and MSMW.

PMID- 24328642
TI  - Understanding the rural-urban differences in nonmedical prescription opioid use
      and abuse in the United States.
AB  - Nonmedical prescription opioid misuse remains a growing public problem in need of
      action and is concentrated in areas of US states with large rural populations
      such as Kentucky, West Virginia, Alaska, and Oklahoma. We developed hypotheses
      regarding the influence of 4 factors: (1) greater opioid prescription in rural
      areas, creating availability from which illegal markets can arise; (2) an out
      migration of young adults; (3) greater rural social and kinship network
      connections, which may facilitate drug diversion and distribution; and (4)
      economic stressors that may create vulnerability to drug use more generally. A
      systematic consideration of the contexts that create differences in availability,
      access, and preferences is critical to understanding how drug use context varies
      across geography. 

PMID- 24328644
TI  - The land of 10,000 tobacco products: how Minnesota led the way in regulating
      tobacco products.
AB  - As state and local governments increase restrictions on cigarette smoking,
      tobacco manufacturers have shifted to marketing alternative tobacco products.
      Tobacco control laws need to be updated to reflect this shifting marketplace.
      With the 2010 enactment of the Tobacco Modernization and Compliance Act,
      Minnesota addressed regulatory gaps and created a model law for other states. We
      have detailed the updated definitions of tobacco and tobacco products and
      identified ways that future laws could be strengthened. 

PMID- 24328643
TI  - Disparities in safety belt use by sexual orientation identity among US high
      school students.
AB  - OBJECTIVES: We examined associations between adolescents' safety belt use and
      sexual orientation identity. METHODS: We pooled data from the 2005 and 2007 Youth
      Risk Behavior Surveys (n = 26,468 weighted; mean age = 15.9 years; 35.4% White,
      24.7% Black, 23.5% Latino, 16.4% other). We compared lesbian and gay (1.2%),
      bisexual (3.5%), and unsure (2.6%) youths with heterosexuals (92.7%) on a binary
      indicator of passenger safety belt use. We stratified weighted multivariable
      logistic regression models by sex and adjusted for survey wave and sampling
      design. RESULTS: Overall, 12.6% of high school students reported "rarely" or
      "never" wearing safety belts. Sexual minority youths had increased odds of
      reporting nonuse relative to heterosexuals (48% higher for male bisexuals, 85%
      for lesbians, 46% for female bisexuals, and 51% for female unsure youths; P <
      .05), after adjustment for demographic (age, race/ethnicity), individual (body
      mass index, depression, bullying, binge drinking, riding with a drunk driver,
      academic achievement), and contextual (living in jurisdictions with secondary or
      primary safety belt laws, percentage below poverty, percentage same-sex
      households) risk factors. CONCLUSIONS: Public health interventions should address
      sexual orientation identity disparities in safety belt use.

PMID- 24328645
TI  - Treating our way out of AIDS?

PMID- 24328646
TI  - Unraveling R0: considerations for public health applications.
AB  - We assessed public health use of R0, the basic reproduction number, which
      estimates the speed at which a disease is capable of spreading in a population.
      These estimates are of great public health interest, as evidenced during the 2009
      influenza A (H1N1) virus pandemic. We reviewed methods commonly used to estimate
      R0, examined their practical utility, and assessed how estimates of this
      epidemiological parameter can inform mitigation strategy decisions. In isolation,
      R0 is a suboptimal gauge of infectious disease dynamics across populations; other
      disease parameters may provide more useful information. Nonetheless, estimation
      of R0 for a particular population is useful for understanding transmission in the
      study population. Considered in the context of other epidemiologically important
      parameters, the value of R0 may lie in better understanding an outbreak and in
      preparing a public health response. 

PMID- 24328647
TI  - Race/Ethnicity, educational attainment, and foregone health care in the United
      States in the 2007-2009 recession.
AB  - OBJECTIVES: This study assessed possible associations between recessions and
      changes in the magnitude of social disparities in foregone health care, building
      on previous studies that have linked recessions to lowered health care use.
      METHODS: Data from the 2006 to 2010 waves of the National Health Interview Study
      were used to examine levels of foregone medical, dental and mental health care
      and prescribed medications. Differences by race/ethnicity and education were
      compared before the Great Recession of 2007 to 2009, during the early recession,
      and later in the recession and in its immediate wake. RESULTS: Foregone care rose
      for working-aged adults overall in the 2 recessionary periods compared with the
      pre-recession. For multiple types of pre-recession care, foregoing care was more
      common for African Americans and Hispanics and less common for Asian Americans
      than for Whites. Less-educated individuals were more likely to forego all types
      of care pre-recession. Most disparities in foregone care were stable during the
      recession, though the African American-White gap in foregone medical care
      increased, as did the Hispanic-White gap and education gap in foregone dental
      care. CONCLUSIONS: Our findings support the fundamental cause hypothesis, as even
      during a recession in which more advantaged groups may have had unusually high
      risk of losing financial assets and employer-provided health insurance, they
      maintained their relative advantage in access to health care. Attention to the
      macroeconomic context of social disparities in health care use is warranted.

PMID- 24328649
TI  - Health status of children of migrant farm workers: Farm Worker Family Health
      Program, Moultrie, Georgia.
AB  - OBJECTIVES: We evaluated the health status of migrant farmworkers' children
      served by the Farm Worker Family Health Program (FWFHP) in Moultrie, Georgia.
      METHODS: We analyzed data from children aged 0 to 16 years examined through the
      FWFHP from 2003 to 2011 (n across years = 179-415). We compared their prevalence
      of overweight, obesity, elevated blood pressure, anemia, and stunting with that
      of children in the United States and Mexico. RESULTS: Across study years,
      prevalence of overweight, obesity, elevated blood pressure, anemia, and stunting
      ranged from 13.5% to 21.8%, 24.0% to 37.4%, 4.1% to 20.2%, 10.1% to 23.9%, and 1%
      to 6.4%, respectively. Children in the FWFHP had a higher prevalence of obesity
      than children in all comparison groups, and FWFHP children aged 6 to 12 years had
      a higher prevalence of elevated blood pressure than all comparison groups. Older
      FWFHP children had a higher prevalence of anemia than US children and Mexican
      children. Children in FWFHP had a higher prevalence of stunting than US and
      Mexican American children. CONCLUSIONS: We observed an elevated prevalence of
      obesity, anemia among older age groups, and stunting in this sample of children
      of migrant workers.

PMID- 24328650
TI  - Sexual orientation disparities in Papanicolaou test use among US women: the role
      of sexual and reproductive health services.
AB  - We investigated sexual orientation disparities in Papanicolaou screening among US
      women aged 21 to 44 years (n = 9581) in the 2006 to 2010 National Survey of
      Family Growth. The odds ratios for lesbian versus heterosexual women and women
      with no versus only male sexual partners were 0.40 and 0.32, respectively, and
      were attenuated after adjustment for sexual and reproductive health (SRH) care
      indicators. Administering Papanicolaou tests through mechanisms other than SRH
      services would promote cervical cancer screening among all women. 

PMID- 24328651
TI  - The role of public health advocacy in achieving an outright ban on commercial
      tanning beds in Australia.
AB  - Although many countries still face opposition to the legislation of artificial
      tanning beds, all Australian states and territories have announced a total ban on
      commercial tanning beds. A combination of epidemiological and policy-centered
      research, powerful personal stories, and the active advocacy of prominent
      academics, cancer organizations, and grassroots community campaigners contributed
      to the decisions to first legislate standards and then ban all commercial tanning
      beds. We have illustrated that incremental change can be an effective pathway to
      securing substantial public health reforms. 

PMID- 24328648
TI  - A systematic review of barriers and facilitators to minority research
      participation among African Americans, Latinos, Asian Americans, and Pacific
      Islanders.
AB  - To assess the experienced or perceived barriers and facilitators to health
      research participation for major US racial/ethnic minority populations, we
      conducted a systematic review of qualitative and quantitative studies from a
      search on PubMed and Web of Science from January 2000 to December 2011. With 44
      articles included in the review, we found distinct and shared barriers and
      facilitators. Despite different expressions of mistrust, all groups represented
      in these studies were willing to participate for altruistic reasons embedded in
      cultural and community priorities. Greater comparative understanding of barriers
      and facilitators to racial/ethnic minorities' research participation can improve
      population-specific recruitment and retention strategies and could better inform
      future large-scale prospective quantitative and in-depth ethnographic studies. 

PMID- 24328652
TI  - Raising sexual minority youths' health levels by incorporating resiliencies into
      health promotion efforts.
AB  - Myriad health inequities that sexual minority youths (SMYs) experience have been
      documented over the past several decades. Evidence demonstrates that these are
      not a result of intrinsic characteristics; rather, they result from high levels
      of adversity that SMYs experience. Despite the pervasive marginalization that
      SMYs face, there is also evidence of great resilience within this population. It
      seems likely that if a culture of marginalization produces health inequities in
      SMYs, a culture of acceptance and integration can work to produce resiliencies.
      We have described how promoting forms of acceptance and integration could work to
      promote resilient SMYs despite an overarching culture of marginalization.
      Building on SMYs' resiliencies may potentiate the effectiveness of health
      promotion interventions to reduce health disparities within this population. 

PMID- 24328653
TI  - Sexual orientation, gender, and racial differences in illicit drug use in a
      sample of US high school students.
AB  - OBJECTIVES: We evaluated drug use differences between sexual minority and
      heterosexual students, including interactions with gender and race/ethnicity.
      METHODS: We used 2005 and 2007 Youth Risk Behavior Survey data pooled from
      Boston, Massachusetts; Chicago, Illinois; Delaware; Maine; Massachusetts; New
      York City, New York; Rhode Island; and Vermont to evaluate drug use (marijuana,
      cocaine, inhalants, heroin, methamphetamine, and MDMA [Ecstasy]) using 2 aspects
      of sexual orientation (identity and sex of sexual partners). RESULTS: Sexual
      minority students had higher prevalence of drug use than did heterosexuals on
      both sexual orientation dimensions, and differences were particularly pronounced
      among bisexual students on both dimensions. Differences between sexual minority
      and heterosexual male students in prevalence were generally larger than were
      differences between sexual minority and heterosexual female students. Racial
      minority students generally reported lower prevalence of drug use. However, the
      protective effect of African American race was less pronounced for some sexual
      minorities. CONCLUSIONS: Sexual minority youths are at increased risk for drug
      use. Intervention is needed at the institutional and individual levels to address
      these disparities.

PMID- 24328654
TI  - High-risk sexual activity in the House and Ball community: influence of social
      networks.
AB  - OBJECTIVES: We investigated the roles of House membership and the influence of
      social and sexual network members on the sexual risk behavior of men in the Los
      Angeles House and Ball community. METHODS: From February 2009 to January 2010,
      male participants (n = 233) completed interviewer-assisted surveys during a House
      meeting or Ball event. We used logistic regression to model the effects of sexual
      network size, influence of sexual network members, House membership status, and
      their interactions on high-risk sex. RESULTS: Significant predictors of high-risk
      sex included number of sexual partners in the nominated social network,
      multiethnicity, and previous diagnosis of sexually transmitted infection. House
      membership was protective against high-risk sex. Additionally, a 3-way
      interaction emerged between number of sexual partners in the network, influence,
      and network members' House membership. CONCLUSIONS: Future research should assess
      network members' attitudes and behavior in detail to provide a greater
      understanding of the dynamics of social influence and to identify additional
      avenues for intervention.

PMID- 24328655
TI  - Gender abuse and major depression among transgender women: a prospective study of
      vulnerability and resilience.
AB  - OBJECTIVES: We examined the social and interpersonal context of gender abuse and
      its effects on Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition major depression among transgender women. METHODS: We conducted a 3-year
      prospective study (2004-2007) among 230 transgender women aged 19 to 59 years
      from the New York City Metropolitan Area. Statistical techniques included
      generalized estimating equations (logistic regression). RESULTS: We observed
      significant associations of psychological and physical gender abuse with major
      depression during follow-up. New or persistent experiences of both types of abuse
      were associated with 4- to 7-fold increases in the likelihood of incident major
      depression. Employment, transgender presentation, sex work, and hormone therapy
      correlated across time with psychological abuse; the latter 2 variables
      correlated with physical abuse. The association of psychological abuse with
      depression was stronger among younger than among older transgender women.
      CONCLUSIONS: Psychological and physical gender abuse is endemic in this
      population and may result from occupational success and attempts to affirm gender
      identity. Both types of abuse have serious mental health consequences in the form
      of major depression. Older transgender women have apparently developed some
      degree of resilience to psychological gender abuse.

PMID- 24328656
TI  - Behavioral adaptation and late-life disability: a new spectrum for assessing
      public health impacts.
AB  - OBJECTIVES: To inform public health efforts to promote independent functioning
      among older adults, we have provided new national estimates of late-life
      disability that explicitly recognize behavioral adaptations. METHODS: We analyzed
      the 2011 National Health and Aging Trends Study, a study of Medicare enrollees
      aged 65 years and older (n = 8077). For 7 mobility and self-care activities we
      identified 5 hierarchical stages--fully able, successful accommodation with
      devices, activity reduction, difficulty despite accommodations, and receipt of
      help--and explored disparities and associations with quality of life measures.
      RESULTS: Among older adults, 31% were fully able to complete self-care and
      mobility activities. The remaining groups successfully accommodated with devices
      (25%), reduced their activities (6%), reported difficulty despite accommodations
      (18%), or received help (21%). With successive stages, physical and cognitive
      capacity decreased and symptoms and multimorbidity increased. Successful
      accommodation was associated with maintaining participation in valued activities
      and high well-being, but substantial disparities by race, ethnicity, and income
      existed. CONCLUSIONS: Increased public health attention to behavioral adaptations
      to functional change can promote independence for older adults and may enhance
      quality of life.

PMID- 24328657
TI  - Obesity, health at every size, and public health policy.
AB  - Obesity is associated with chronic diseases that may negatively affect
      individuals' health and the sustainability of the health care system. Despite
      increasing emphasis on obesity as a major health care issue, little progress has
      been made in its treatment or prevention. Individual approaches to obesity
      treatment, largely composed of weight-loss dieting, have not proven effective.
      Little direct evidence supports the notion of reforms to the "obesogenic
      environment." Both these individualistic and environmental approaches to obesity
      have important limitations and ethical implications. The low levels of success
      associated with these approaches may necessitate a new non-weight-centric public
      health strategy. Evidence is accumulating that a weight-neutral, nutrition- and
      physical activity-based, Health at Every Size (HAES) approach may be a promising
      chronic disease-prevention strategy. 

PMID- 24328659
TI  - "A campaign won as a public issue will stay won": using cartoons and comics to
      fight national health care reform, 1940s and beyond.
AB  - On March 23, 2010, President Barack Obama signed the Patient Protection and
      Affordable Care Act (ACA) into law. As it went through Congress, the legislation
      faced forceful resistance. Individuals and organizations opposing the ACA
      circulated propaganda that varied from photographs of fresh graves or coffins
      with the caption "Result of ObamaCare" to portrayals of President Obama as the
      Joker from the Batman movies, captioned with the single word "socialism." The
      arguments embedded in these images have striking parallels to cartoons circulated
      by physicians to their patients in earlier fights against national health care.
      Examining cartoons used in the formative health care reform debates of the 1940s
      provides a means for tracing the lineage of emotional arguments employed against
      health care reform. 

PMID- 24328658
TI  - Sexual orientation and suicide ideation, plans, attempts, and medically serious
      attempts: evidence from local Youth Risk Behavior Surveys, 2001-2009.
AB  - OBJECTIVES: We examined the associations between 2 measures of sexual orientation
      and 4 suicide risk outcomes (SROs) from pooled local Youth Risk Behavior Surveys.
      METHODS: We aggregated data from 5 local Youth Risk Behavior Surveys from 2001 to
      2009. We defined sexual minority youths (SMYs) by sexual identity (lesbian, gay,
      bisexual) and sex of sexual contacts (same- or both-sex contacts). Survey
      logistic regression analyses controlled for a wide range of suicide risk factors
      and sample design effects. RESULTS: Compared with non-SMYs, all SMYs had
      increased odds of suicide ideation; bisexual youths, gay males, and both-sex
      contact females had greater odds of suicide planning; all SMYs, except same-sex
      contact males, had increased odds of suicide attempts; and lesbians, bisexuals,
      and both-sex contact youths had increased odds of medically serious attempts.
      Unsure males had increased odds of suicide ideation compared with heterosexual
      males. Not having sexual contact was protective of most SROs among females and of
      medically serious attempts among males. CONCLUSIONS: Regardless of sexual
      orientation measure used, most SMY subgroups had increased odds of all SROs.
      However, many factors are associated with SROs.

PMID- 24328660
TI  - Identifying armed respondents to domestic violence restraining orders and
      recovering their firearms: process evaluation of an initiative in California.
AB  - OBJECTIVES: We evaluated a law enforcement initiative to screen respondents to
      domestic violence restraining orders for firearm ownership or possession and
      recover their firearms. METHODS: The initiative was implemented in San Mateo and
      Butte counties in California from 2007 through 2010. We used descriptive methods
      to evaluate the screening process and recovery effort in each county, relying on
      records for individual cases. RESULTS: Screening relied on an archive of firearm
      transactions, court records, and petitioner interviews; no single source was
      adequate. Screening linked 525 respondents (17.7%) in San Mateo County to
      firearms; 405 firearms were recovered from 119 (22.7%) of them. In Butte County,
      88 (31.1%) respondents were linked to firearms; 260 firearms were recovered from
      45 (51.1%) of them. Nonrecovery occurred most often when orders were never served
      or respondents denied having firearms. There were no reports of serious violence
      or injury. CONCLUSIONS: Recovering firearms from persons subject to domestic
      violence restraining orders is possible. We have identified design and
      implementation changes that may improve the screening process and the yield from
      recovery efforts. Larger implementation trials are needed.

PMID- 24328661
TI  - When health policy and empirical evidence collide: the case of cigarette package
      warning labels and economic consumer surplus.
AB  - In its graphic warning label regulations on cigarette packages, the Food and Drug
      Administration severely discounts the benefits of reduced smoking because of the
      lost "pleasure" smokers experience when they stop smoking; this is quantified as
      lost "consumer surplus." Consumer surplus is grounded in rational choice theory.
      However, empirical evidence from psychological cognitive science and behavioral
      economics demonstrates that the assumptions of rational choice are inconsistent
      with complex multidimensional decisions, particularly smoking. Rational choice
      does not account for the roles of emotions, misperceptions, optimistic bias,
      regret, and cognitive inefficiency that are germane to smoking, particularly
      because most smokers begin smoking in their youth. Continued application of a
      consumer surplus discount will undermine sensible policies to reduce tobacco use
      and other policies to promote public health. 

PMID- 24328663
TI  - Broadening the scope for national database sampling: a critical need.

PMID- 24328662
TI  - The association between sexual orientation identity and behavior across
      race/ethnicity, sex, and age in a probability sample of high school students.
AB  - OBJECTIVES: We examined the prevalence and associations between behavioral and
      identity dimensions of sexual orientation among adolescents in the United States,
      with consideration of differences associated with race/ethnicity, sex, and age.
      METHODS: We used pooled data from 2005 and 2007 Youth Risk Behavior Surveys to
      estimate prevalence of sexual orientation variables within demographic sub
      groups. We used multilevel logistic regression models to test differences in the
      association between sexual orientation identity and sexual behavior across
      groups. RESULTS: There was substantial incongruence between behavioral and
      identity dimensions of sexual orientation, which varied across sex and
      race/ethnicity. Whereas girls were more likely to identify as bisexual, boys
      showed a stronger association between same-sex behavior and a bisexual identity.
      The pattern of association of age with sexual orientation differed between boys
      and girls. CONCLUSIONS: Our results highlight demographic differences between 2
      sexual orientation dimensions, and their congruence, among 13- to 18-year-old
      adolescents. Future research is needed to better understand the implications of
      such differences, particularly in the realm of health and health disparities.

PMID- 24328664
TI  - Anti-gay prejudice and all-cause mortality among heterosexuals in the United
      States.
AB  - OBJECTIVES: We determined whether individuals who harbor antigay prejudice
      experience elevated mortality risk. METHODS: Data on heterosexual sexual
      orientation (n = 20,226, aged 18-89 years), antigay attitudes, and mortality risk
      factors came from the General Social Survey, which was linked to mortality data
      from the National Death Index (1988-2008). We used Cox proportional hazard models
      to examine whether antigay prejudice was associated with mortality risk among
      heterosexuals. RESULTS: Heterosexuals who reported higher levels of antigay
      prejudice had higher mortality risk than those who reported lower levels (hazard
      ratio [HR] = 1.25; 95% confidence interval [CI] = 1.09, 1.42), with control for
      multiple risk factors for mortality, including demographics, socioeconomic
      status, and fair or poor self-rated health. This result translates into a life
      expectancy difference of approximately 2.5 years (95% CI = 1.0, 4.0 years)
      between individuals with high versus low levels of antigay prejudice.
      Furthermore, in sensitivity analyses, antigay prejudice was specifically
      associated with increased risk of cardiovascular-related causes of death in fully
      adjusted models (HR = 1.29; 95% CI = 1.04, 1.60). CONCLUSIONS: The findings
      contribute to a growing body of research suggesting that reducing prejudice may
      improve the health of both minority and majority populations.

PMID- 24328665
TI  - Research funded by the National Institutes of Health on the health of lesbian,
      gay, bisexual, and transgender populations.
AB  - OBJECTIVES: We examined the proportion of studies funded by the National
      Institutes of Health (NIH) that focused on lesbian, gay, bisexual, and
      transgender (LGBT) populations, along with investigated health topics. METHODS:
      We used the NIH RePORTER system to search for LGBT-related terms in NIH-funded
      research from 1989 through 2011. We coded abstracts for LGBT inclusion,
      subpopulations studied, health foci, and whether studies involved interventions.
      RESULTS: NIH funded 628 studies concerning LGBT health. Excluding projects about
      HIV/AIDS and other sexual health matters, only 0.1% (n = 113) of all NIH-funded
      studies concerned LGBT health. Among the LGBT-related projects, 86.1% studied
      sexual minority men, 13.5% studied sexual minority women, and 6.8% studied
      transgender populations. Overall, 79.1% of LGBT-related projects focused on
      HIV/AIDS and substantially fewer on illicit drug use (30.9%), mental health
      (23.2%), other sexual health matters (16.4%), and alcohol use (12.9%). Only 202
      studies examined LGBT health-related interventions. Over time, the number of LGBT
      related projects per year increased. CONCLUSIONS: The lack of NIH-funded research
      about LGBT health contributes to the perpetuation of health inequities. Here we
      recommend ways for NIH to stimulate LGBT-related research.

PMID- 24328666
TI  - A longitudinal analysis of the effect of nonmedical exemption law and vaccine
      uptake on vaccine-targeted disease rates.
AB  - OBJECTIVES: We assessed how nonmedical exemption (NME) laws and annual uptake of
      vaccines required for school or daycare entry affect annual incidence rates for 5
      vaccine-targeted diseases: pertussis, measles, mumps, Haemophilus influenzae type
      B, and hepatitis B. METHODS: We employed longitudinal mixed-effects models to
      examine 2001-2008 vaccine-targeted disease data obtained from the National
      Notifiable Disease Surveillance System. Key explanatory variables were state
      level vaccine-specific uptake rates from the National Immunization Survey and a
      state NME law restrictiveness level. RESULTS: NME law restrictiveness and vaccine
      uptake were not associated with disease incidence rate for hepatitis B,
      Haemophilus influenzae type B, measles, or mumps. Pertussis incidence rate,
      however, was negatively associated with NME law restrictiveness (b = -0.20; P =
      .03) and diphtheria-pertussis-tetanus vaccine uptake (b = -0.01; P = .05).
      CONCLUSIONS: State NME laws and vaccine uptake rates did not appear to influence
      lower-incidence diseases but may influence reported disease rates for higher
      incidence diseases. If all states increased their NME law restrictiveness by 1
      level and diphtheria-pertussis-tetanus uptake by 1%, national annual pertussis
      cases could decrease by 1.14% (171 cases) and 0.04% (5 cases), respectively.

PMID- 24328667
TI  - Economic and political influence on tobacco tax rates: a nationwide analysis of
      31 years of state data.
AB  - OBJECTIVES: We evaluated state-level characteristics associated with cigarette
      excise taxes before and after the Master Settlement Agreement (MSA). METHODS: We
      gathered annual cigarette excise tax rates for all US states and the District of
      Columbia, between 1981 and 2011, and matched each state-year tax rate with
      economic, political, attitudinal, and demographic characteristics, creating a
      data set of 1581 observations. We used panel data regression techniques to assess
      relationships between key characteristics and state cigarette excise tax levels.
      RESULTS: Cigarette excise tax rates grew at more than 6 times the rate of
      inflation between 1981 and 2011; growth varied by time period and region. We
      found strong negative associations between Republican Party control of state
      legislatures and governors' offices and state cigarette tax rates. Tobacco
      production, citizens' attitudes toward taxes and tobacco control, and cigarette
      tax rates in neighboring states were significantly associated with cigarette tax
      rates. We found no association between unemployment and tax rates. CONCLUSIONS:
      Future excise tax growth rate may depend more on the political leanings of state
      legislators, and the attitudes of the people they represent, than on economic
      circumstances.

PMID- 24328668
TI  - A G57W Mutation of CRYGS Associated with Autosomal Dominant Pulverulent Cataracts
      in a Chinese Family.

PMID- 24328669
TI  - Statement of retraction: Hongying Lv, Qicai Li, Wengsheng Qiu, Jinyu Xiang,
      Hongjun Wei, Hua Liang, Aihua Sui and Jun Liang "Genetic polymorphism of XRCC1
      correlated with response to oxaliplatin-based chemotherapy in advanced colorectal
      cancer".

PMID- 24328671
TI  - Interrupted time series design: a useful approach for studying interventions
      targeting participation.
AB  - Comparative effectiveness research (CER) strives for evidence to inform clinical
      decisions for specific clients in typical health care settings. While the
      randomized controlled trial (RCT) is well-aligned with the objectives of CER,
      this design may not be feasible or applicable to all research questions,
      particularly those pertaining to clinical decision making and individually based
      change. It is important, therefore, to consider alternative approaches,
      especially when studying complex and subjective outcomes such as children's
      participation. We propose the use of interrupted time series (ITS) quasi
      experimental design for its potential application in determining the
      effectiveness of participation-focused interventions. In this perspective, ITS
      design is described, ascertaining its advantages and limitations, and suggestions
      are provided to overcome challenges to implementation. Results of a case study
      using the ITS approach to evaluate changes in participation of an adolescent with
      physical disabilities are described. Finally, strategies to implement this design
      in practice are suggested.

PMID- 24328672
TI  - Optimization of fermentation medium for acetoin production by Bacillus subtilis
      SF4-3 using statistical methods.
AB  - To improve the acetoin-producing ability of Bacillus subtilis SF4-3, isolated
      from "natto," a Japanese traditional food, the fermentation medium was optimized
      in shake-flask fermentation by statistically designed methods. Based on results
      of the single-factor experiment, orthogonal experiment, and Plackett-Burman
      design, yeast extract, corn steep liquor, and urea were identified as showing
      significant influence on the acetoin production. Subsequently, the optimum
      combination of the three factors was investigated by the Box-Behnken design (BBD)
      of response surface methodology (RSM) in order to further enhance the acetoin
      production. The maximum acetoin yield of 45.4 g/L was predicted when the
      concentrations of yeast extract, corn steep liquor, and urea were 8.5 g/L, 14.6
      g/L, and 3.8 g/L, respectively. The results were further confirmed in triplicate
      experiments using the optimized medium (glucose 160 g/L, yeast extract 8.5 g/L,
      corn steep liquor 14.6 g/L, urea 3.8 g/L, manganese sulfate 0.05 g/L, ferrous
      sulfate 0.05 g/L), and an acetoin yield of 46.2 g/L was obtained in the
      validation experiment, which was in agreement with the prediction. After the
      optimization of medium components, an increase of 36.28% in acetoin production
      was achieved in comparison to that at the initial medium levels. 

PMID- 24328670
TI  - Mechanotransduction in the endothelium: role of membrane proteins and reactive
      oxygen species in sensing, transduction, and transmission of the signal with
      altered blood flow.
AB  - SIGNIFICANCE: Changes in shear stress associated with alterations in blood flow
      initiate a signaling cascade that modulates the vascular phenotype. Shear stress
      is "sensed" by the endothelium via a mechanosensitive complex on the endothelial
      cell (EC) membrane that has been characterized as a "mechanosome" consisting of
      caveolae, platelet endothelial cell adhesion molecule (PECAM), vascular
      endothelial growth factor receptor 2 (VEGFR2), vascular endothelial (VE)
      cadherin, and possibly other elements. This shear signal is transduced by cell
      membrane ion channels and various kinases and results in the activation of NADPH
      oxidase (type 2) with the production of reactive oxygen species (ROS). RECENT
      ADVANCES: The signaling cascade associated with stop of shear, as would occur in
      vivo with various obstructive pathologies, leads to cell proliferation and
      eventual revascularization. CRITICAL ISSUES AND FUTURE DIRECTIONS: Although
      several elements of mechanosensing such as the sensing event, the transduction,
      transmission, and reception of the mechanosignal are now reasonably well
      understood, the links among these discrete steps in the pathway are not clear.
      Thus, identifying the mechanisms for the interaction of the K(ATP) channel, the
      kinases, and ROS to drive long-term adaptive responses in ECs is necessary. A
      critical re-examination of the signaling events associated with complex flow
      patterns (turbulent, oscillatory) under physiological conditions is also
      essential for the progress in the field. Since these complex shear patterns may
      be associated with an atherosclerosis susceptible phenotype, a specific challenge
      will be the pharmacological modulation of the responses to altered signaling
      events that occur at specific sites of disturbed or obstructed flow.

PMID- 24328673
TI  - Nonparametric tests of associations with disease based on U-statistics.
AB  - In case-control studies, association analysis was designed to test whether
      genetic variants were associated with human diseases. To evaluate the
      association, analysing one genetic marker at a time suffered from weak power,
      because of the correction for multiple testing and possibly small genetic
      effects. An alternative strategy was to test simultaneous effects of multiple
      markers, which was believed to be more powerful. However, when the number of
      markers under investigation was large, they would be subjected to weak power as
      well, because of the greater degrees of freedom. To conquer these limitations in
      case-control studies, we proposed a novel method that could test joint
      association of several loci (i.e. haplotype), with only a single degree of
      freedom. In this research, we developed a nonparametric approach, which was based
      on U-statistics. We also introduced a new kernel for U-statistic, which could
      combine the haplotype structure information, and was expected to enhance the
      power. Simulations indicated that our proposed approach offered merits in
      identifying the associations between diseases and haplotypes. Application of our
      method to a study of candidate genes for internalising disorder illustrated its
      virtue in utility and interpretation, and provided an excellent result in
      detecting the associations. 

PMID- 24328674
TI  - Endothelial dysfunction and carotid atherosclerosis in non-alcoholic fatty liver
      disease.

PMID- 24328675
TI  - Two new furostanol saponins from the fibrous root of Ophiopogon japonicus.
AB  - Two new furostanol saponins ophiopogonins J (1) and K (2) were isolated from the
      fibrous roots of Ophiopogon japonicus. The structures of 1 and 2 were established
      as (25R)-26-O-[(beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl)]-14
      hydroxy-furost-5,20(22)-diene 3-O-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D
      glucopyranoside (1), and (25R)-26-O-[(beta-D-glucopyranosyl-(1 --> 2)-beta-D
      glucopyranosyl)]-furost-5,20(22)-diene 3-O-alpha-L-rhamnopyranosyl-(1 -->
      2)[(beta-D-xylopyranosyl-(1 --> 4)-beta-D-glucopyranoside)] (2) on the basis of
      spectroscopic means including HRESIMS, 1D, and 2D NMR experiments.

PMID- 24328676
TI  - beta-sitosteryl-3-O-beta-glucopyranoside isolated from the bark of Sorbus
      commixta ameliorates pro-inflammatory mediators in RAW 264.7 macrophages.
AB  - The bark of Sorbus commixta has been used in Asian traditional medicine for
      treatment of cough, asthma, bronchial disorders, gastritis and dropsy. However,
      the anti-inflammatory effect of beta-sitosteryl-3-O-beta-glucopyranoside, a major
      compound of the bark of S. commixta, is poorly understood. In this study, we
      investigated the anti-inflammatory effect and the underlying molecular mechanisms
      of beta-sitosteryl-3-O-beta-glucopyranoside in lipopolysaccharide (LPS)-induced
      RAW 264.7 cells. Prostaglandin E2 (PGE2) and cytokines released from cells were
      measured using EIA assay kit. The expression of inducible NO synthase (iNOS) and
      cyclooxygenase (COX)-2, Tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta), and interleukin-6 (IL-6) was measured by real-time polymerase
      chain reaction (RT-PCR) and/or Western blot analysis. beta-sitosteryl-3-O-beta
      glucopyranoside inhibited the production of nitric oxide (NO) and PGE2 along with
      the expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. In addition,
      beta-sitosteryl-3-O-beta-glucopyranoside reduced the release of pro-inflammatory
      cytokines, such as TNF-alpha, IL-1beta and IL-6. Moreover, beta-sitosteryl-3-O
      beta-glucopyranoside inhibited the NF-kappaB activation induced by LPS, which was
      associated with the abrogation of IkappaBalpha degradation and subsequent
      decreases in nuclear p65 levels. The result suggested that the beta-sitosteryl-3
      O-beta-glucopyranoside inhibited NO and pro-inflammatory productions by down
      regulating the gene expression of pro-inflammatory mediators via the negative
      regulation of the NF-kB pathway in LPS-stimulated RAW 264.7 cells.

PMID- 24328677
TI  - Effects of oral administration of di-(2-ethylhexyl) and diisononyl phthalates on
      atopic dermatitis in NC/Nga mice.
AB  - CONTEXT: Subcutaneous injection of low dose of phthalates causes adjuvant effects
      on immunoglobulin production. Moreover, intraperitoneal injection of di-(2
      ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP) at doses lower than
      the no-observed-adverse-effect level (NOAEL) causes aggravation of atopic
      dermatitis-like skin lesions (ADSLs) in mouse models. However, the effects of
      oral exposure to these phthalates, including their effect on atopic dermatitis
      (AD) symptoms, remain unclear. OBJECTIVE: To investigate the effects of oral
      administration of DEHP and DINP at doses lower than the NOAEL on AD in an NC/Nga
      mouse model. MATERIALS AND METHODS: NC/Nga mice were subcutaneously injected with
      mite-allergen (Dermatophagoides pteronyssinus) to induce ADSLs and orally
      administered varying doses of DEHP (0, 8.3, 166.3 or 3325 ug/animal) or DINP (0,
      6.6, 131.3 or 2625 ug/animal) once a week for four weeks. Skin disease
      symptomatology was subsequently evaluated and immunoglobulin production levels in
      serum and inflammatory cytokine levels in lesion sites were measured. RESULTS:
      Oral administration of low doses of both DEHP and DINP tended to increase
      infiltration of eosinophils; degranulation of mast cells and local expression of
      inflammatory cytokines, interleukin-13 and macrophage inflammatory protein-1
      alpha in subcutaneous tissue, whereas DINP administration tended to aggravate
      allergen-induced ADSL production. CONCLUSIONS: Oral administration of both DEHP
      and DINP at doses lower than the NOAEL tends to increase the allergic response in
      animal AD models, but only DINP administration slightly aggravates allergen
      induced ADSL production.

PMID- 24328678
TI  - Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by
      inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the
      E3 ubiquitin ligase complex CRL4(CRBN.).
AB  - Cereblon (CRBN), the molecular target of lenalidomide and pomalidomide, is a
      substrate receptor of the cullin ring E3 ubiquitin ligase complex, CRL4(CRBN) . T
      cell co-stimulation by lenalidomide or pomalidomide is cereblon dependent:
      however, the CRL4(CRBN) substrates responsible for T cell co-stimulation have yet
      to be identified. Here we demonstrate that interaction of the transcription
      factors Ikaros (IKZF1, encoded by the IKZF1 gene) and Aiolos (IKZF3, encoded by
      the IKZF3 gene) with CRL4(CRBN) is induced by lenalidomide or pomalidomide. Each
      agent promotes Aiolos and Ikaros binding to CRL4(CRBN) with enhanced
      ubiquitination leading to cereblon-dependent proteosomal degradation in T
      lymphocytes. We confirm that Aiolos and Ikaros are transcriptional repressors of
      interleukin-2 expression. The findings link lenalidomide- or pomalidomide-induced
      degradation of these transcriptional suppressors to well documented T cell
      activation. Importantly, Aiolos could serve as a proximal pharmacodynamic marker
      for lenalidomide and pomalidomide, as healthy human subjects administered
      lenalidomide demonstrated Aiolos degradation in their peripheral T cells. In
      conclusion, we present a molecular model in which drug binding to cereblon
      results in the interaction of Ikaros and Aiolos to CRL4(CRBN) , leading to their
      ubiquitination, subsequent proteasomal degradation and T cell activation.

PMID- 24328679
TI  - A novel approach for C-C, C-N, and C-O bond formation reactions: a facile
      synthesis of benzophenazine, quinoxaline, and phenoxazine derivatives via ring
      opening of benzoxepines.
AB  - A new one-pot protocol has been developed for the synthesis of benzophenazine,
      quinoxaline, and phenoxazine derivatives by the reaction of benzoxepine-4
      carboxylates with benzene-1,2-diamines, ethane-1,2-diamine, and 2-aminophenols in
      the presence of Bi(OTf)3 (5 mol %) under mild conditions in very good yields. The
      present protocol opens a new way for C-C, C-N, and C-O bond-formation reactions
      in a single-step process. The structural assignment was confirmed by X-ray
      analysis. 

PMID- 24328681
TI  - 4,9-Dihydro-4,4,9,9-tetrahexyl-s-indaceno[1,2-b:5,6-b']dithiophene as a pi-spacer
      of donor-pi-acceptor dye and its photovoltaic performance with liquid and solid
      state dye-sensitized solar cells.
AB  - A new D-pi-A organic dye, LC-5, containing 4,9-dihydro-4,4,9,9-tetrahexyl-s
      indaceno[1,2-b:5,6-b']-dithiophene as a novel pi-conjugated spacer has been
      synthesized and tested as a sensitizer in dye-sensitized solar cells (DSC).
      Volatile and ionic liquid electrolytes have been used in conjunction with the
      synthesized dye, and the electrolyte influence on the photovoltaic performance of
      DSCs was investigated. A detailed investigation, including transient
      photocurrent/photovoltage decay measurements and electrochemical impedance
      spectroscopy data, provide important conclusions about the influence of
      electrolytes on the photovoltaic parameters. 

PMID- 24328680
TI  - Role of glycogenolysis in stimulation of ATP release from cultured mouse
      astrocytes by transmitters and high K+ concentrations.
AB  - This study investigates the role of glycogenolysis in stimulated release of ATP
      as a transmitter from astrocytes. Within the last 20 years our understanding of
      brain glycogenolysis has changed from it being a relatively uninteresting process
      to being a driving force for essential brain functions like production of
      transmitter glutamate and homoeostasis of potassium ions (K+) after their release
      from excited neurons. Simultaneously, the importance of astrocytic handling of
      adenosine, its phosphorylation to ATP and release of some astrocytic ATP, located
      in vesicles, as an important transmitter has also become to be realized. Among
      the procedures stimulating Ca2+-dependent release of vesicular ATP are exposure
      to such transmitters as glutamate and adenosine, which raise intra-astrocytic
      Ca2+ concentration, or increase of extracellular K+ to a depolarizing level that
      opens astrocytic L-channels for Ca2+ and thereby also increase intra-astrocytic
      Ca2+ concentration, a prerequisite for glycogenolysis. The present study has
      confirmed and quantitated stimulated ATP release from well differentiated
      astrocyte cultures by glutamate, adenosine or elevated extracellular K+
      concentrations, measured by a luciferin/luciferase reaction. It has also shown
      that this release is virtually abolished by an inhibitor of glycogenolysis as
      well as by inhibitors of transmitter-mediated signaling or of L-channel opening
      by elevated K+ concentrations. 

PMID- 24328682
TI  - Improvement of solubility and targetability of radioiodinated hypericin by using
      sodium cholate based solvent in rat models of necrosis.
AB  - Hypericin (Hyp) is newly recognized as a necrosis avid agent, but its poor
      solubility imposes a great hindrance in clinical application. The aim of this
      paper was to explore sodium cholate (NaCh) as a potential solvent for Hyp and
      assess the targetability of (131)I-Hyp in rat necrosis models. Hyp solubility in
      NaCh solutions was evaluated by equilibrium solubility measurement.
      Biodistribution of (131)I-Hyp in NaCh solutions and mixed organic solvents was
      investigated in rat models of liver and muscle necrosis examined with MRI and
      SPECT/CT in vivo. In addition, pharmacokinetics of (131)I-Hyp in NaCh solutions
      was studied in healthy rats. Results showed NaCh could improve Hyp solubility and
      (131)I-Hyp incubated in NaCh solutions/rat plasma was stable up to 120 h. On
      SPECT/CT images at 24 h post injection, liver infarction location appeared as hot
      spots. Liver necrosis-to-liver ratios were 12.2, 10.0, 9.6 and 8.2 in 60, 15, 2
      mmol/L of NaCh solutions and organic solvents, and muscle necrosis-to-liver
      ratios were 11.1, 10.1, 7.7 and 7.4, respectively. Pharmacokinetics study
      revealed t(1/2)z (11.93, 8.96 h, p > 0.05) and AUC (0-infinity) (421.21, 553.34
      MBq/L h, p < 0.05) of (131)I-Hyp in 2, 60 mmol/L of NaCh solutions, respectively.
      In conclusion, NaCh was an effective cosolvent, and the necrosis avidity of NaCh
      dissolved (131)I-Hyp/Hyp was demonstrated.

PMID- 24328683
TI  - Pemphigus vulgaris autoimmune globulin induces Src-dependent tyrosine
      phosphorylation of plakophilin 3 and its detachment from desmoglein 3.
AB  - The cell adhesion molecule plakophilin 3 (Pkp3) plays an essential role in the
      maintenance of skin integrity and is targeted in certain autoimmune conditions.
      In one example, we have shown that Pkp3 is instrumental in mediating the
      discohesive effects of sera from patients with pemphigus vulgaris (PV), a life
      threatening autoimmune disease that targets intercellular adhesion in the
      epidermis. In the present study, we determine the effect of PV autoimmune
      globulin (PV IgG) on Pkp3 in an in-vitro model of PV. We demonstrate that Pkp3
      becomes tyrosine phosphorylated as early as 30 min upon binding of PV IgG to
      keratinocyte surface and eventually detaches from its binding partner desmoglein
      3 (Dsg3). In parallel, Pkp3 is depleted from the membrane (Triton X-soluble)
      fraction and accumulates in the cytoplasm within 240 min of incubation with PV
      IgG. Inhibition of Pkp3 phosphorylation by a Src inhibitor attenuates the
      discohesive effects of PV IgG. Taken together, the data demonstrate that
      activation of Src-kinase signalling is crucial for PV acantholysis and acts, at
      least in part, via phosphorylation of the adaptor protein Pkp3.

PMID- 24328684
TI  - Methotrexate- and cyclophosphamide-embedded pure and strontiumsubstituted
      carbonate apatite nanoparticles for augmentation of chemotherapeutic activities
      in breast cancer cells.
AB  - Most of the classical drugs used today to destroy cancer cells lead to the
      development of acquired resistance in those cells by limiting cellular entry of
      the drugs or exporting them out by efflux pumps. As a result, higher doses of
      drugs are usually required to kill the cancer cells affecting normal cells and
      causing numerous side effects. Accumulation of the therapeutic level of drugs
      inside the cancer cells is thus required for an adequate period of time to get
      drugs' complete therapeutic efficacy minimizing the side effects on normal cells.
      In order to improve the efficacy of chemotherapeutic drugs, nanoparticles of
      carbonate apatite and its strontium (Sr(2+))-substituted derivative were used in
      this study to make complexes with three classical anticancer drugs, methotrexate,
      cyclophosphamide and 5-flurouracil. The binding affinities of these drugs to
      apatite were evaluated by absorbance and HPLC analysis and the therapeutic
      efficacy of drug-apatite complexes was determined by cell viability assay.
      Carbonate apatite demonstrated significant binding affinity towards methotrexate
      and cyclophosphamide leading to more cellular toxicity than free drugs in MCF-7
      and 4T1 breast cancer cells. Moreover, Sr(2+) substitution in carbonate apatite
      with resulting tiny particles less than 100 nm in diameter further promoted
      binding of methotrexate to the nanocarriers indicating that Sr(2+)-substituted
      apatite nanoparticles have the high potential for loading substantial amount of
      anti-cancer drugs with eventual more therapeutic effectiveness. 

PMID- 24328685
TI  - Correlates of service delivery and social environment in adult day service
      programs.
AB  - The objectives of this study were to better describe adult day service (ADS)
      programs and determine how various structural and case mix characteristics of ADS
      were empirically associated with the services provided in and the social
      environments of adult day programs. All directors of ADS programs in Minnesota
      (United States) were contacted from 2011 to 2012 to complete a detailed online
      survey that collected information on ADS structure, client case mix, services and
      activities, and social environment (n = 83; 67.5% response rate). Several
      structural characteristics and case mix indicators (e.g., number of clients
      attending) were significantly associated (p < .05) with specific types of ADS
      service provision, such as health monitoring. Programs that were adequately
      staffed and perceived as pleasant appeared to also have a more vibrant social
      environment. The results suggest the potential need for bolstering staffing and
      enhancing the physical environment of ADS programs. 

PMID- 24328686
TI  - The mechanism, efficacy, and tolerability profile of agomelatine.
AB  - INTRODUCTION: Agomelatine is a novel antidepressant that acts as a melatonin MT1
      and MT2 receptor agonist and serotonin 5-HT2C receptor antagonist, putatively
      reversing circadian rhythm disruption in major depressive disorder (MDD) and
      promoting dendritic neurogenesis in animal models of depression. It may be a
      preferable alternative to antidepressants currently in use due to its improved
      tolerability profile. AREAS COVERED: The PubMed database was searched for
      published randomized controlled trials (RCTs) evaluating the efficacy of
      agomelatine as well as its tolerability and safety in the treatment of MDD. The
      key search term used was agomelatine combined with major depressive
      disorder/depressive disorder/depression and antidepressant. Article selection was
      based upon sample size and overall methodological quality. EXPERT OPINION:
      Agomelatine is a multi-modal agent with novel mechanisms of action, having sound
      evidence supporting its overall statistical efficacy and adequate tolerability
      profile for MDD treatment. However, the clinical significance of agomelatine has
      been contested, calling for additional studies in evaluation of its effect size.
      Of further concern are reported transient elevations in transaminases and severe
      but rare liver reactions.

PMID- 24328687
TI  - Optimizing topographical templates for directed self-assembly of block copolymers
      via inverse design simulations.
AB  - An inverse design algorithm has been developed that predicts the necessary
      topographical template needed to direct the self-assembly of a diblock copolymer
      to produce a given complex target structure. The approach is optimized by varying
      the number of topographical posts, post size, and block copolymer volume fraction
      to yield a template solution that generates the target structure in a
      reproducible manner. The inverse algorithm is implemented computationally to
      predict post arrangements that will template two different target structures and
      the predicted templates are tested experimentally with a polydimethylsiloxane-b
      polystyrene block copolymer. Simulated and experimental results show overall very
      good agreement despite the complexity of the patterns. The templates determined
      from the model can be used in developing simpler design rules for block copolymer
      directed self-assembly. 

PMID- 24328689
TI  - Evaluation of awareness of risk factors for kidney cancer among patients
      presenting to a urology clinic.
AB  - OBJECTIVE: This study aimed to evaluate awareness of risk factors for kidney
      cancer among patients presenting to a urology clinic. Smoking, obesity and
      hypertension are widely accepted as risk factors for kidney cancer; however,
      there are limited data regarding awareness of these risk factors. MATERIAL AND
      METHODS: The researchers prospectively identified 172 patients presenting to a
      urology clinic between 1 May 2009 and 31 August 2009. Each patient completed a
      questionnaire that requested responses to whether certain lifestyle factors
      increased the risk of a variety of cancers. Information on demographics and other
      covariates was collected via questionnaires and medical chart abstraction. To
      estimate and compare risk factor awareness levels for different cancers, 95%
      confidence intervals (95% CIs) were constructed and Fisher's exact tests
      performed. Logistic regression analysis was used to evaluate covariates
      associated with risk factor awareness. RESULTS: The percentage reporting that
      smoking increases the risk of kidney cancer (36%, 95% CI 29-44%) was lower than
      for lung cancer (96%, 95% CI 92-99%). Similarly, the percentage reporting that
      obesity increases the risk of kidney cancer (32%, 95% CI 25-40%) was lower than
      for colon cancer (45%, 95% CI 37-53% CI). Only 18% (95% CI 13-25%) identified
      hypertension as a risk factor for kidney cancer. Female gender and younger age
      were associated with increased levels of awareness of the association with
      smoking and obesity, respectively. CONCLUSION: The data support a low level of
      awareness of kidney cancer risk factors and underscore an opportunity for
      urologists to engage in education efforts.

PMID- 24328688
TI  - Reactive nitrogen species and hydrogen sulfide as regulators of protein tyrosine
      phosphatase activity.
AB  - SIGNIFICANCE: Redox modifications of thiols serve as a molecular code enabling
      precise and complex regulation of protein tyrosine phosphatases (PTPs) and other
      proteins. Particular gasotransmitters and even the redox modifications themselves
      affect each other, of which a typical example is S-nitrosylation-mediated
      protection against the further oxidation of protein thiols. RECENT ADVANCES: For
      a long time, PTPs were considered constitutively active housekeeping enzymes.
      This view has changed substantially over the last two decades, and the PTP family
      is now recognized as a group of tightly and flexibly regulated fundamental
      enzymes. In addition to the conventional ways in which they are regulated,
      including noncovalent interactions, phosphorylation, and oxidation, the evidence
      that has accumulated during the past two decades suggests that many of these
      enzymes are also modulated by gasotransmitters, namely by nitric oxide (NO) and
      hydrogen sulfide (H2S). CRITICAL ISSUES: The specificity and selectivity of the
      methods used to detect nitrosylation and sulfhydration remains to be
      corroborated, because several researchers raised the issue of false-positive
      results, particularly when using the most widespread biotin switch method.
      Further development of robust and straightforward proteomic methods is needed to
      further improve our knowledge of the full extent of the gasotransmitters-mediated
      changes in PTP activity, selectivity, and specificity. FURTHER DIRECTIONS:
      Results of the hitherto performed studies on gasotransmitter-mediated PTP
      signaling await translation into clinical medicine and pharmacotherapeutics. In
      addition to directly affecting the activity of particular PTPs, the use of
      reversible S-nitrosylation as a protective mechanism against oxidative stress
      should be of high interest.

PMID- 24328690
TI  - Impact of various factors on pharmacokinetics of bioactive polyphenols: an
      overview.
AB  - Several epidemiological studies throughout the years have suggested that
      polyphenols from fruits and vegetables promote health and reduce the risk of
      certain chronic and neurodegenerative diseases. Yet, it has been proved to be
      extremely difficult to quantitatively establish the benefit afforded by
      polyphenols, principally due to the limited understanding of the extent of its
      absorption and metabolic fate. Pharmacokinetics includes the study of the
      mechanisms of absorption and distribution of an ingested polyphenol, its chemical
      changes in the body (e.g. by metabolic enzymes), and the effects and routes of
      excretion of the metabolites. In recent years, there have been major advances in
      our knowledge of polyphenol absorption and metabolism, and it is apparent that
      most classes of polyphenols are sufficiently absorbed to have the potential to
      exert biological effects. The pharmacokinetics of polyphenols includes the same
      steps as those for orally ingested drugs (LADME) and faces some of the same
      challenges, including transporters and enzymes. However, unraveling the
      bioavailability of polyphenols is even more challenging than with drugs, since
      many other factors, such as the variety in the chemical structure, the food
      matrix and the gut microbiota, can affect bioavailability of polyphenols during
      digestion. This review focuses on the most relevant factors that influence
      polyphenol pharmacokinetics, and also on the most recent technological strategies
      developed to overcome the poor bioavailability of phenolic compounds and thus
      increase their potential for greater health benefits. 

PMID- 24328691
TI  - Delivery and application of dietary polyphenols to target organs, tissues and
      intracellular organelles.
AB  - At present, dietary polyphenols are popular with consumers because regular
      consumption of polyphenol-rich foods is likely to be beneficial for human health.
      However, administrated polyphenols are extensively metabolized in the digestive
      tract or some other parts before reaching the target organs. Additionally, some
      of the polyphenols are photosensitive, easily oxidized and are in unfavorable
      forms. Therefore, a lot of work has been performed to ensure delivery of intact
      polyphenols to the target organs. We here summarize recent progress in polyphenol
      delivery to individual organs, tissues, and cells, in regard to relatively new
      delivery systems. Polyphenol-delivery systems can be divided into three
      categories: (i) before delivery into the blood stream (skin, mouth,
      gastrointestine), (ii) in the blood stream (plasma), and (iii) after the blood
      stream (brain, spleen, bone marrow, kidney). Polyphenols before the delivery into
      blood stream must overcome several obstacles to avoid converting into inactive
      forms by commensal microorganisms, environmental pH, and some others. In the
      blood, plasma-polyphenol interactions and modifications are very effective for
      the bioavailability of polyphenols with numerous enzymes. Native forms of
      polyphenols, successfully out of the blood stream, further go through obstacles
      such as the blood brain barrier to reach target organs. Recent progress in
      delivering polyphenols is here discussed on 3 main delivery systems,
      nanoparticle, liposome, and microemulsion. Moreover, we also focused on delivery
      systems to intracellular organelles (cell surface, lysosome, mitochondria,
      nucleus), which are the final targets of polyphenols to perform their beneficial
      reactions. 

PMID- 24328692
TI  - Influence of diabetes on the pharmacokinetic behavior of natural polyphenols.
AB  - The development of food fortified with polyphenols and polyphenol-rich foods
      represents a novel approach to prevent or attenuate type 2 diabetes. It has been
      reported that type 2 diabetes may affect the pharmacokinetics of various drugs in
      several animal models. There is powerful evidence linking dietary polyphenols
      consumption with the risk factors defining type 2 diabetes, even if some opposite
      results occurred. This mini-review summarizes important advances on diabetes
      associated changes in pharmacokinetics of natural polyphenols. The
      pharmacokinetic behavior between drugs and dietary polyphenols probably may be
      different due to (i) Ingested dose/amount per day. The dietary polyphenol intake
      per day is much higher than that of clinical drugs; (ii) Complexity of the
      components. Clinical drugs are well-characterized and typically small molecules.
      However, the polyphenols in diet are unimaginably complex; (iii) Interaction with
      food proteins. Although the effects of food proteins on the bioavailability of
      polyphenols are still not examined in much detail, direct binding interactions of
      polyphenols to proteins always occur; (iv) The most common polyphenols in the
      human diet have a low intrinsic activity and are poorly absorbed from the
      intestine, highly metabolized, or rapidly eliminated. Although there is very
      limited information available so far, it is proposed that type 2 diabetes
      influences the pharmacokinetic behavior of dietary polyphenols including: i)
      competition of glucose with polyphenols regarding binding to plasma proteins; ii)
      weakened non-covalent interaction affinities of plasma proteins for natural
      polyphenols due to protein glycation in type II diabetes; iii) the enhanced
      clearance of polyphenols in type 2 diabetes. An understanding of diabetes
      associated changes in absorption, distribution, metabolism, elimination and
      bioactivities of natural polyphenols as well as the mechanism of the variability
      should lead to the improvement of the benefits of these polyphenols and clinical
      outcomes for diabetics. 

PMID- 24328693
TI  - Concealed Jiggling Effect: A Novel Risk Factor for Complications of Implant
      Supported Fixed Partial Denture.

PMID- 24328698
TI  - Self-efficacy as a relevant construct in understanding sexual response and
      dysfunction.
AB  - While self-efficacy has been widely used to explain and treat various
      biobehavioral responses, few investigations have examined this concept in the
      context of sexual response and dysfunction. In this study, the authors
      constructed a measure of sexual self-efficacy, investigated whether it
      differentiated men with and without sexual dysfunction, and determined the
      utility of this construct by exploring its relation to other variables known to
      be related to erectile dysfunction in a sample of 60 men with erectile
      dysfunction and 14 functional men visiting a urology clinic. The sexual self
      efficacy index differentiated men with and without erectile dysfunction, and
      general linear modeling showed that the index did indeed relate to other
      variables known to affect sexual and emotional response during a partnered sexual
      experience. These findings suggest that, as a unifying construct that predicts
      cognitive, affective, motivational, and behavioral responses, sexual self
      efficacy has the potential to play an important role in the assessment of
      effective treatments for sexual problems. 

PMID- 24328694
TI  - Circadian dysfunction in response to in vivo treatment with the mitochondrial
      toxin 3-nitropropionic acid.
AB  - Sleep disorders are common in neurodegenerative diseases including Huntington's
      disease (HD) and develop early in the disease process. Mitochondrial alterations
      are believed to play a critical role in the pathophysiology of neurodegenerative
      diseases. In the present study, we evaluated the circadian system of mice after
      inhibiting mitochondrial complex II of the respiratory chain with the toxin 3
      nitropropionic acid (3-NP). We found that a subset of mice treated with low doses
      of 3-NP exhibited severe circadian deficit in behavior. The temporal patterning
      of sleep behavior is also disrupted in some mice with evidence of difficulty in
      the initiation of sleep behavior. Using the open field test during the normal
      sleep phase, we found that the 3-NP-treated mice were hyperactive. The molecular
      clockwork responsible for the generation of circadian rhythms as measured by
      PER2::LUCIFERASE was disrupted in a subset of mice. Within the SCN, the 3-NP
      treatment resulted in a reduction in daytime firing rate in the subset of mice
      which had a behavioral deficit. Anatomically, we confirmed that all of the
      treated mice showed evidence for cell loss within the striatum but we did not see
      evidence for gross SCN pathology. Together, the data demonstrates that chronic
      treatment with low doses of the mitochondrial toxin 3-NP produced circadian
      deficits in a subset of treated mice. This work does raise the possibility that
      the neural damage produced by mitochondrial dysfunction can contribute to the
      sleep/circadian dysfunction seen so commonly in neurodegenerative diseases. 

PMID- 24328699
TI  - Honey and cardiovascular risk factors, in normal individuals and in patients with
      diabetes mellitus or dyslipidemia.
AB  - Diabetes mellitus, hypercholesteremia, hypertension (HTN), and obesity are well
      known risk factors for cardiovascular diseases (CVD). Various medications are
      currently in use for management of these comorbidities. Undesirable side effects
      are unavoidable and the ultimate and ideal goal is hardly achieved. Honey and
      other bee products are widely used in traditional medicine for management of many
      diseases. Others and the authors have found potent biological activities of these
      products. Honey is now reintroduced in modern medicine as part of wound and burn
      management. Honey has antioxidant, anti-inflammatory, and antimicrobial
      activities. More studies are exploring other aspects of honey activity such as
      its effect on blood sugar, body weight, lipid profile, C-reactive protein, nitric
      oxide, proinflammatory prostaglandins, and homocysteine. Growing evidence and
      scientific data support the use of honey in patients with diabetes, HTN,
      dyslipidemia, obesity, and CVD. This review discusses clinical and preclinical
      studies on potential influence of honey on diabetes mellitus and cardiovascular
      risk factors, and emphasizes the importance of conducting more clinical and
      controlled studies.

PMID- 24328700
TI  - Antimicrobial effects of virgin coconut oil and its medium-chain fatty acids on
      Clostridium difficile.
AB  - Clostridium difficile is the leading cause of hospital-acquired antibiotic
      associated diarrhea worldwide; in addition, the proliferation of antibiotic
      resistant C. difficile is becoming a significant problem. Virgin coconut oil
      (VCO) has been shown previously to have the antimicrobial activity. This study
      evaluates the lipid components of VCO for the control of C. difficile. VCO and
      its most active individual fatty acids were tested to evaluate their
      antimicrobial effect on C. difficile in vitro. The data indicate that exposure to
      lauric acid (C12) was the most inhibitory to growth (P<.001), as determined by a
      reduction in colony-forming units per milliliter. Capric acid (C10) and caprylic
      acid (C8) were inhibitory to growth, but to a lesser degree. VCO did not inhibit
      the growth of C. difficile; however, growth was inhibited when bacterial cells
      were exposed to 0.15-1.2% lipolyzed coconut oil. Transmission electron microscopy
      (TEM) showed the disruption of both the cell membrane and the cytoplasm of cells
      exposed to 2 mg/mL of lauric acid. Changes in bacterial cell membrane integrity
      were additionally confirmed for VCO and select fatty acids using Live/Dead
      staining. This study demonstrates the growth inhibition of C. difficile mediated
      by medium-chain fatty acids derived from VCO.

PMID- 24328701
TI  - Assessment of pharmacokinetic interaction of spirulina with glitazone in a type 2
      diabetes rat model.
AB  - The objective of the current study was to assess the possible pharmacokinetic
      interactions of spirulina with glitazones in an insulin resistance rat model.
      Wistar male albino rats were equally divided into five groups: insulin resistant
      rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant
      rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500
      mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg),
      and insulin resistant rats+spirulina (500 mg/kg). Described doses of
      pioglitazone, rosiglitazone, or spirulina were per orally administered and the
      plasma drug concentrations were determined. The pharmacokinetic parameters such
      as Tmax, Cmax, AUC(0-alpha), t1/2, and Kel were determined by plotting the drug
      concentration as a function of time. The data observed in this acute study
      indicated that there was no statistically significant difference in any of the
      pharmacokinetic parameters (Tmax, Cmax, AUC(0-alpha), t1/2, and Kel) of
      glitazones (pioglitazone, rosiglitazone) or spirulina, when they were
      coadministered. Given the promising results, this study concludes that the
      coadministration of spirulina does not influence the pharmacokinetics of
      glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are
      recommended to assess the real time effect.

PMID- 24328702
TI  - Proapoptotic and antimetastatic properties of supercritical CO2 extract of
      Nigella sativa Linn. against breast cancer cells.
AB  - Nigella sativa, commonly referred as black cumin, is a popular spice that has
      been used since the ancient Egyptians. It has traditionally been used for
      treatment of various human ailments ranging from fever to intestinal disturbances
      to cancer. This study investigated the apoptotic, antimetastatic, and anticancer
      activities of supercritical carbon dioxide (SC-CO2) extracts of the seeds of N.
      sativa Linn. against estrogen-dependent human breast cancer cells (MCF-7). Twelve
      extracts were prepared from N. sativa seeds using the SC-CO2 extraction method by
      varying pressure and temperature. Extracts were analyzed using FTIR and UV-Vis
      spectrometry. Cytotoxicity of the extracts was evaluated on various human cancer
      and normal cell lines. Of the 12 extracts, 1 extract (A3) that was prepared at 60
      degrees C and 2500 psi (~17.24 MPa) showed selective antiproliferative activity
      against MCF-7 cells with an IC50 of 53.34+/-2.15 MUg/mL. Induction of apoptosis
      was confirmed by evaluating caspases activities and observing the cells under a
      scanning electron microscope. In vitro antimetastatic properties of A3 were
      investigated by colony formation, cell migration, and cell invasion assays. The
      elevated levels of caspases in A3 treated MCF-7 cells suggest that A3 is
      proapoptotic. Further nuclear condensation and fragmentation studies confirmed
      that A3 induces cytotoxicity through the apoptosis pathway. A3 also demonstrated
      remarkable inhibition in migration and invasion assays of MCF-7 cells at
      subcytotoxic concentrations. Thus, this study highlights the therapeutic
      potentials of SC-CO2 extract of N. sativa in targeting breast cancer.

PMID- 24328703
TI  - Antioxidant capacity of food mixtures is not correlated with their
      antiproliferative activity against MCF-7 breast cancer cells.
AB  - Combining different foods may produce additive, synergistic, or antagonistic
      interactions that may modify certain physiological effects (i.e., anticancer
      properties). For investigating these interactions and potential synergetic
      combinations, thirteen foods from three categories, including fruits
      (raspberries, blackberries, apples, grapes), vegetables (broccoli, tomatoes,
      mushrooms, purple cauliflowers, onions), and legumes (soy beans, adzuki beans,
      red kidney beans, black beans), were evaluated for their inhibitory activity
      against MCF-7 breast cancer cells. Grape, onion, and adzuki bean showed maximal
      growth inhibition of MCF-7 from the fruit, vegetable, and legume groups,
      respectively. When these three foods were combined in pairs, unique interactions
      were observed that were not seen when individual extracts were used. Combining
      onion and grape resulted in a synergistic antiproliferative effect (APE) against
      MCF-7 compared with either onion or grape treatment alone. In contrast, combining
      grape and adzuki bean resulted in an antagonistic interaction. Additionally, four
      antioxidant assays (total phenolic contents, ferric reducing antioxidant power,
      2,2-diphenyl-1-picrylhydrazyl, and oxygen radical absorbance capacity) were
      further used to evaluate the antioxidant capacities (AC) of individual foods and
      their combinations. Combining raspberry and adzuki bean extracts demonstrated
      synergistic AC in all four assays, but they did not show synergistic APE against
      the MCF-7 cells. Combining broccoli and soy produced antioxidant antagonism, but
      did not have an antagonistic APE against MCF-7. The synergistic or antagonistic
      AC of food mixtures did not correlate with the synergistic or antagonistic APE
      against MCF-7. Further investigation is to determine the mechanisms of these
      interactions and to predict and enhance the therapeutic benefits of foods and
      food components through strategic food combinations.

PMID- 24328704
TI  - Developmental effects of dietary nucleotides in second-generation weaned rats.
AB  - The aim of the present study was to evaluate dietary effects of dietary
      nucleotides (NTs) on developmental parameters in second-generation Sprague-Dawley
      rats. Experimental design was set up as six groups, including one control and
      five nucleotide administered groups, doses ranged from 0.01% to 1.28%
      nucleotides. First-generation (F0) rats were divided into two terms: (1) fed for
      90-day study; (2) mated for offspring (F1). After weaning, each group of second
      generation F1 rats was fed the control diet. Evaluating parameters were weight
      gain and food utilization ratios of rats, hematological and biochemical
      parameters, and organ pathology. The results showed that there was a greater
      weight gain and food utilization ratio in weaned rats (F0 and F1). Furthermore,
      weight gain and food utilization ratios were increased in the first 2 weeks of F1
      male and the first week of F1 female rats. There were no significant changes in
      blood indicators of NT groups with the exception of decrease in aspartate
      aminotransferase and serum uric acid levels. Overall, it was demonstrated that NT
      supplements could promote the early growth and development at a 0.01% dose.
      Although NTs may have cumulative reproductive effects, they were safe even at a
      high-dose supplementation. Additionally, NT supplementation could promote
      restoration and optimize liver function.

PMID- 24328705
TI  - Healing actions of essential oils from Citrus aurantium and d-limonene in the
      gastric mucosa: the roles of VEGF, PCNA, and COX-2 in cell proliferation.
AB  - Previous studies have described the gastroprotective effects of essential oils
      that are derived from Citrus aurantium (OEC) and its main compound d-limonene
      (LIM) in a model of chemically induced ulcers in rats. However, these studies do
      not address the compound's healing effects on the gastric mucosa. Thus, the aim
      of this work was to evaluate the healing activity of OEC and LIM in acetic acid
      induced gastric ulcers in rats, a model that reproduces human chronic ulcers. The
      obtained results demonstrated that lower effective doses of OEC (250 mg/kg) and
      LIM (245 mg/kg) induced gastric mucosal healing with a cure rate of 44% and 56%,
      respectively, compared with the control group (P<.05). During the 14 days of OEC
      or LIM treatment, none of the groups demonstrated toxicity in terms of body and
      organ weight or serum biochemical parameters. Both OEC and LIM treatment promoted
      an increase in epithelial healing, as confirmed by immunohistochemistry, which
      was greater in the animals that were treated with the positive control. In
      addition, both treatments increased cellular proliferation as measured by
      proliferating cell nuclear antigen and cyclooxygenase 2 expression in the gastric
      mucosa, vascular endothelial growth factor-mediated blood vessel formation in the
      margin of the ulcer, and production of gastric mucus, which fortifies the gastric
      protective barrier. We concluded that OEC and LIM, two common flavoring agents,
      promote gastric mucosal healing without any apparent toxic effect, resulting in
      better gastric epithelial organization in the treated rats.

PMID- 24328707
TI  - Absolute determination of single-stranded and self-complementary adeno-associated
      viral vector genome titers by droplet digital PCR.
AB  - Accurate titration of adeno-associated viral (AAV) vector genome copies is
      critical for ensuring correct and reproducible dosing in both preclinical and
      clinical settings. Quantitative PCR (qPCR) is the current method of choice for
      titrating AAV genomes because of the simplicity, accuracy, and robustness of the
      assay. However, issues with qPCR-based determination of self-complementary AAV
      vector genome titers, due to primer-probe exclusion through genome self-annealing
      or through packaging of prematurely terminated defective interfering (DI)
      genomes, have been reported. Alternative qPCR, gel-based, or Southern blotting
      titering methods have been designed to overcome these issues but may represent a
      backward step from standard qPCR methods in terms of simplicity, robustness, and
      precision. Droplet digital PCR (ddPCR) is a new PCR technique that directly
      quantifies DNA copies with an unparalleled degree of precision and without the
      need for a standard curve or for a high degree of amplification efficiency; all
      properties that lend themselves to the accurate quantification of both single
      stranded and self-complementary AAV genomes. Here we compare a ddPCR-based AAV
      genome titer assay with a standard and an optimized qPCR assay for the titration
      of both single-stranded and self-complementary AAV genomes. We demonstrate
      absolute quantification of single-stranded AAV vector genomes by ddPCR with up to
      4-fold increases in titer over a standard qPCR titration but with equivalent
      readout to an optimized qPCR assay. In the case of self-complementary vectors,
      ddPCR titers were on average 5-, 1.9-, and 2.3-fold higher than those determined
      by standard qPCR, optimized qPCR, and agarose gel assays, respectively. Droplet
      digital PCR-based genome titering was superior to qPCR in terms of both intra-
      and interassay precision and is more resistant to PCR inhibitors, a desirable
      feature for in-process monitoring of early-stage vector production and for vector
      genome biodistribution analysis in inhibitory tissues.

PMID- 24328709
TI  - Organ-specific solutions and strategies for the intestinal preservation.
AB  - Among the intraabdominal organs, the intestine is the most susceptible to storage
      injury and as a consequence its safe cold ischemic time in the clinic is
      restricted to below 10 hours. The current practice for the intestinal
      preservation (IP) consists of an in-situ vascular flush with iced University of
      Wisconsin or Histidine-Tryptophan-Ketoglutarate solution followed by cold storage
      at 4 degrees C. Mucosal injury is initiated within 1 hour and rapidly progresses
      to mucosal breakdown; tissue injury worsens upon reperfusion and further impairs
      the mucosal barrier, favoring bacterial translocation and sepsis. In addition of
      releasing danger signals, an advanced ischemia-reperfusion injury (IRI) may
      increase graft immunogenicity and promote rejection. Several alternative
      approaches have been tested as alternatives to the static storage. The aim of
      this review is to summarize and discuss the various intraluminal interventions as
      additional strategies aiming to reduce the IP/reperfusion injury and highlight
      the underlying pathophysiological mechanisms. 

PMID- 24328710
TI  - Current status of allograft tolerance in intestinal transplantation.
AB  - Solid organ transplantation has become a clinical practice after the development
      of different immunosuppressive drugs that allowed controlling rejection. The
      price to be paid for that is the permanent risk of infections and malignancies
      and a significant drug-associated toxicity. The establishment of transplant
      tolerance has been the "holy grail" for transplantation medicine since its
      beginnings. Different experimental approaches and clinical trials resulted in the
      accumulation of knowledge on mechanisms and strategies that favor the
      establishment of tolerance without achieving the objective of autonomous
      allograft tolerance in the clinical field. Development of tolerance in intestinal
      transplantation constitutes a challenging situation due to several particular
      features that contribute to the generation of a strong allogeneic response. In
      the present review, we summarize the different immune mechanisms that may
      contribute to allograft tolerance. The different barriers that should be bypassed
      in intestinal transplantation to tolerate the graft are discussed. Finally, we
      revise the strategies that were applied with different degrees of success in the
      clinical field including the most promising recent approaches and the forthcoming
      candidates in the field that might be translated into clinical trials in the near
      future. 

PMID- 24328708
TI  - Cardiovascular gene therapy for myocardial infarction.
AB  - INTRODUCTION: Cardiovascular gene therapy is the third most popular application
      for gene therapy, representing 8.4% of all gene therapy trials as reported in
      2012 estimates. Gene therapy in cardiovascular disease is aiming to treat heart
      failure from ischemic and non-ischemic causes, peripheral artery disease, venous
      ulcer, pulmonary hypertension, atherosclerosis and monogenic diseases, such as
      Fabry disease. AREAS COVERED: In this review, we will focus on elucidating
      current molecular targets for the treatment of ventricular dysfunction following
      myocardial infarction (MI). In particular, we will focus on the treatment of i)
      the clinical consequences of it, such as heart failure and residual myocardial
      ischemia and ii) etiological causes of MI (coronary vessels atherosclerosis,
      bypass venous graft disease, in-stent restenosis). EXPERT OPINION: We summarise
      the scheme of the review and the molecular targets either already at the gene
      therapy clinical trial phase or in the pipeline. These targets will be discussed
      below. Following this, we will focus on what we believe are the 4 prerequisites
      of success of any gene target therapy: safety, expression, specificity and
      efficacy (SESE).

PMID- 24328711
TI  - Calibrating sensitivity analyses to observed covariates in observational studies.
AB  - In medical sciences, statistical analyses based on observational studies are
      common phenomena. One peril of drawing inferences about the effect of a treatment
      on subjects using observational studies is the lack of randomized assignment of
      subjects to the treatment. After adjusting for measured pretreatment covariates,
      perhaps by matching, a sensitivity analysis examines the impact of an unobserved
      covariate, u, in an observational study. One type of sensitivity analysis uses
      two sensitivity parameters to measure the degree of departure of an observational
      study from randomized assignment. One sensitivity parameter relates u to
      treatment and the other relates u to response. For subject matter experts, it may
      be difficult to specify plausible ranges of values for the sensitivity parameters
      on their absolute scales. We propose an approach that calibrates the values of
      the sensitivity parameters to the observed covariates and is more interpretable
      to subject matter experts. We will illustrate our method using data from the U.S.
      National Health and Nutrition Examination Survey regarding the relationship
      between cigarette smoking and blood lead levels.

PMID- 24328712
TI  - Efficient semiparametric estimation of short-term and long-term hazard ratios
      with right-censored data.
AB  - The proportional hazards assumption in the commonly used Cox model for censored
      failure time data is often violated in scientific studies. Yang and Prentice
      (2005) proposed a novel semiparametric two-sample model that includes the
      proportional hazards model and the proportional odds model as sub-models, and
      accommodates crossing survival curves. The model leaves the baseline hazard
      unspecified and the two model parameters can be interpreted as the short-term and
      long-term hazard ratios. Inference procedures were developed based on a pseudo
      score approach. Although extension to accommodate covariates was mentioned, no
      formal procedures have been provided or proved. Furthermore, the pseudo score
      approach may not be asymptotically efficient. We study the extension of the short
      term and long-term hazard ratio model of Yang and Prentice (2005) to accommodate
      potentially time-dependent covariates. We develop efficient likelihood-based
      estimation and inference procedures. The nonparametric maximum likelihood
      estimators are shown to be consistent, asymptotically normal, and asymptotically
      efficient. Extensive simulation studies demonstrate that the proposed methods
      perform well in practical settings. The proposed method successfully captured the
      phenomenon of crossing hazards in a cancer clinical trial and identified a
      genetic marker with significant long-term effect missed by using the proportional
      hazards model on age-at-onset of alcoholism in a genetic study. 

PMID- 24328713
TI  - Omnibus risk assessment via accelerated failure time kernel machine modeling.
AB  - Integrating genomic information with traditional clinical risk factors to improve
      the prediction of disease outcomes could profoundly change the practice of
      medicine. However, the large number of potential markers and possible complexity
      of the relationship between markers and disease make it difficult to construct
      accurate risk prediction models. Standard approaches for identifying important
      markers often rely on marginal associations or linearity assumptions and may not
      capture non-linear or interactive effects. In recent years, much work has been
      done to group genes into pathways and networks. Integrating such biological
      knowledge into statistical learning could potentially improve model
      interpretability and reliability. One effective approach is to employ a kernel
      machine (KM) framework, which can capture nonlinear effects if nonlinear kernels
      are used (Scholkopf and Smola, 2002; Liu et al., 2007, 2008). For survival
      outcomes, KM regression modeling and testing procedures have been derived under a
      proportional hazards (PH) assumption (Li and Luan, 2003; Cai, Tonini, and Lin,
      2011). In this article, we derive testing and prediction methods for KM
      regression under the accelerated failure time (AFT) model, a useful alternative
      to the PH model. We approximate the null distribution of our test statistic using
      resampling procedures. When multiple kernels are of potential interest, it may be
      unclear in advance which kernel to use for testing and estimation. We propose a
      robust Omnibus Test that combines information across kernels, and an approach for
      selecting the best kernel for estimation. The methods are illustrated with an
      application in breast cancer. 

PMID- 24328714
TI  - Linear score tests for variance components in linear mixed models and
      applications to genetic association studies.
AB  - Following the rapid development of genome-scale genotyping technologies, genetic
      association mapping has become a popular tool to detect genomic regions
      responsible for certain (disease) phenotypes, especially in early-phase
      pharmacogenomic studies with limited sample size. In response to such
      applications, a good association test needs to be (1) applicable to a wide range
      of possible genetic models, including, but not limited to, the presence of gene
      by-environment or gene-by-gene interactions and non-linearity of a group of
      marker effects, (2) accurate in small samples, fast to compute on the genomic
      scale, and amenable to large scale multiple testing corrections, and (3)
      reasonably powerful to locate causal genomic regions. The kernel machine method
      represented in linear mixed models provides a viable solution by transforming the
      problem into testing the nullity of variance components. In this study, we
      consider score-based tests by choosing a statistic linear in the score function.
      When the model under the null hypothesis has only one error variance parameter,
      our test is exact in finite samples. When the null model has more than one
      variance parameter, we develop a new moment-based approximation that performs
      well in simulations. Through simulations and analysis of real data, we
      demonstrate that the new test possesses most of the aforementioned
      characteristics, especially when compared to existing quadratic score tests or
      restricted likelihood ratio tests. 

PMID- 24328716
TI  - Letter to the editor: "Comment on Hubbard and Miglioretti (2013), consider also a
      selection model for the cumulative risk of false positive screening tests".

PMID- 24328715
TI  - Bayesian latent-class mixed-effect hybrid models for dyadic longitudinal data
      with non-ignorable dropouts.
AB  - The analysis of longitudinal dyadic data is challenging due to the complicated
      correlations within and between dyads, as well as possibly non-ignorable
      dropouts. Based on a mixed-effects hybrid model, we propose an approach to
      analyze longitudinal dyadic data with non-ignorable dropouts. We factorize the
      joint distribution of the measurement and dropout processes into three
      components: the marginal distribution of random effects, the conditional
      distribution of the dropout process given the random effects, and the conditional
      distribution of the measurement process given the random effects and missing data
      patterns. We model the conditional dropout process using a discrete survival
      model, and the conditional measurement process using a latent-class pattern
      mixture model. These models account for the dyadic interdependence using the
      "actor" and "partner" effects and dyad-specific random effects. We use the latent
      dropout-class approach to address the problem of a large number of missing data
      patterns caused by the dyadic data structure. We evaluate the performance of the
      proposed method using a simulation study, and apply our method to a longitudinal
      dyadic data set that arose from a prostate cancer trial. 

PMID- 24328717
TI  - A new dipeptide isolated from the bulb of garlic.
AB  - (R)-3-(allylthio)-2-((R)-3-(allylthio)-2-aminopropanamido)propanoic acid was
      isolated from the bulb of garlic, together with four known amino acids. Its
      structure was elucidated on the basis of 2D NMR and MS techniques. To the best of
      our knowledge, (R)-3-(allylthio)-2-((R)-3-(allylthio)-2
      aminopropanamido)propanoic acid, which showed antibacterial activity against the
      Staphylococcus aureus antibiotic resistant strain, was the first example of
      dipeptide from garlic. 

PMID- 24328718
TI  - Rh(III)-catalyzed intermolecular C-H amination of 1-aryl-1H-pyrazol-5(4H)-ones
      with alkylamines.
AB  - An intermolecular C-H amination of 1-aryl-1H-pyrazol-5(4H)-ones was achieved
      under mild reaction conditions, using a low catalyst loading and with a broad
      scope of aminating reagents. This protocol not only provides the first example of
      rhodium(III)-catalyzed intermolecular aromatic C-H amination directed by an
      intrinsic functionality of the substrate/product but also features aminating an
      existing drug with either primary or secondary N-benzoate alkylamines as the
      coupling partners.

PMID- 24328719
TI  - Use of safety measures, including the modified world health organization surgical
      safety checklist, during international outreach cleft missions.
AB  - International surgical outreach missions have become increasingly common within
      the surgery community. Untoward events in this setting, although rare, can be
      prevented by careful planning and the use of quality assurance guidelines
      designed to prevent such complications. The surgical safety checklist is widely
      accepted in most developed health care practices, but is used variably by
      international mission groups. This article outlines the quality assurance
      guidelines used, including a modified World Health Organization safety checklist
      and illustrated patient instruction forms, to provide a standardized means of
      delivering sound surgical care in the setting of short-term international cleft
      lip and/or palate missions. 

PMID- 24328720
TI  - Treatment of motor fluctuations in Parkinson's disease: recent developments and
      future directions.
AB  - Parkinson's disease (PD) is characterized clinically by rest tremor, rigidity,
      bradykinesia and pathologically by degeneration of nigrostriatal dopamine
      neurons. Motor fluctuations (wearing off) and motor complications (dyskinesia)
      are common features of the long-term treatment of PD. Ongoing clinical and
      preclinical research has led to the discovery of promising new therapeutic
      targets that might prevent or reduce motor complications. Newer approaches
      modulating non-dopaminergic systems including adenosine A2A antagonists,
      monoamine oxidase-B inhibitors, glutamatergic antagonists, adrenergic receptor
      antagonists and serotonergic agents are encouraging strategies for management of
      advanced PD. Recent developments in levodopa delivery formulations include
      duodenal infusion of a levodopa/carbidopa, new extended-release levodopa and oral
      pro-levodopa forms. Recent clinical trials revealed diverse but promising results
      raising the possibility of new therapeutic modalities for PD in the near future. 

PMID- 24328721
TI  - ABM--a global, multispeciality organization.

PMID- 24328723
TI  - Arylamine N-acetyltransferases: a structural perspective. Comments regarding the
      BJP paper by Zhou et al., 2013.

PMID- 24328724
TI  - An overview of inverted colloidal crystal systems for tissue engineering.
AB  - Scaffolding is at the heart of tissue engineering but the number of techniques
      available for turning biomaterials into scaffolds displaying the features
      required for a tissue engineering application is somewhat limited. Inverted
      colloidal crystals (ICCs) are inverse replicas of an ordered array of
      monodisperse colloidal particles, which organize themselves in packed long-range
      crystals. The literature on ICC systems has grown enormously in the past 20
      years, driven by the need to find organized macroporous structures. Although
      replicating the structure of packed colloidal crystals (CCs) into solid
      structures has produced a wide range of advanced materials (e.g., photonic
      crystals, catalysts, and membranes) only in recent years have ICCs been evaluated
      as devices for medical/pharmaceutical and tissue engineering applications. The
      geometry, size, pore density, and interconnectivity are features of the scaffold
      that strongly affect the cell environment with consequences on cell adhesion,
      proliferation, and differentiation. ICC scaffolds are highly geometrically
      ordered structures with increased porosity and connectivity, which enhances
      oxygen and nutrient diffusion, providing optimum cellular development. In
      comparison to other types of scaffolds, ICCs have three major unique features:
      the isotropic three-dimensional environment, comprising highly uniform and size
      controllable pores, and the presence of windows connecting adjacent pores. Thus
      far, this is the only technique that guarantees these features with a long-range
      order, between a few nanometers and thousands of micrometers. In this review, we
      present the current development status of ICC scaffolds for tissue engineering
      applications. 

PMID- 24328722
TI  - Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on
      cardiovascular function in conscious rats.
AB  - BACKGROUND AND PURPOSE: The cardiovascular effects produced by 3,4
      methylenedioxymethamphetamine (MDMA; 'Ecstasy') contribute to its acute toxicity,
      but the potential role of its metabolites in these cardiovascular effects is not
      known. Here we examined the effects of MDMA metabolites on cardiovascular
      function in rats. EXPERIMENTAL APPROACH: Radiotelemetry was employed to evaluate
      the effects of s.c. administration of racemic MDMA and its phase I metabolites on
      BP, heart rate (HR) and locomotor activity in conscious male rats. KEY RESULTS:
      MDMA (1-20 mg.kg(-1)) produced dose-related increases in BP, HR and activity. The
      peak effects on HR occurred at a lower dose than peak effects on BP or activity.
      The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced
      effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine
      (HHMA; 1-10 mg.kg(-1)) increased HR more potently and to a greater extent than
      MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent
      than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4
      hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA)
      did not affect any of the parameters measured. The tachycardia produced by MDMA
      and HHMA was blocked by the beta-adrenoceptor antagonist propranolol. CONCLUSIONS
      AND IMPLICATIONS: Our results demonstrate that HHMA may contribute significantly
      to the cardiovascular effects of MDMA in vivo. As such, determining the molecular
      mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants
      further study.

PMID- 24328725
TI  - Development of novel topical drug delivery system containing cisplatin and
      imiquimod for dual therapy in cutaneous epithelial malignancy.
AB  - CONTEXT: Strategy of dual therapy has been proposed to minimize the amount of
      each drug and to achieve the synergistic effect for cancer therapies. OBJECTIVE:
      The aim of this study was to develop an effective drug delivery system for the
      simultaneous topical delivery of two anti-tumor agents, cisplatin and imiquimod.
      MATERIAL AND METHODS: The preformulation studies were carried out in terms of
      tests for identification, solubility profile, determination of partition
      coefficient and simultaneous estimation of both drugs by UV-Visible
      spectrophotometer and High Performance Liquid Chromatography (HPLC). Drug-drug
      and drug-excipients interactions were examined by thin layer chromatography,
      infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray
      diffraction (XRD). Provesicular drug delivery system (protransfersome gel
      formulation) have been prepared and characterized by in vitro and in vivo
      parameters. RESULTS: The mean size, poly dispersity index (PDI) and zeta
      potential of transfersomal vesicles formed by protransfersome hydration were
      429.5 nm, 0.631 and -68.1 Mv, respectively. The prepared formulation showed
      toxicity on cutaneous squamous cell carcinoma cell line (A-431) at 200 ug
      (cisplatin) and 1 mg (imiquimod) concentration of drug in combination against
      control. The cisplatin- and imiquimod-loaded provesicular dual-drug delivery
      system achieved an optimal antitumor effect, increase in lifespan, antiviral, and
      toxicity reduction, revealing the advantage of site specific drug delivery and
      the modified combination therapy. DISCUSSION: Cisplatin delivery through
      protransfersome gel in combination with imiquimod may potentiate the activity
      against solid tumors of epidermal origin. CONCLUSION: Data revealed that
      combination therapy considerably enhances antitumor efficacy of the drug for skin
      cited malignancies.

PMID- 24328726
TI  - Medicare home health care patient case-mix before and after the Balanced Budget
      Act of 1997: effect on dual eligible beneficiaries.
AB  - The Balanced Budget Act (BBA) of 1997 changed the payment system for Medicare
      home health care (HHC) from cost-based to prospective reimbursement. We used
      Medical Expenditure Panel Survey data to assess the impact of the BBA on Medicare
      HHC patient case-mix measured by the Centers for Medicare and Medicaid Services
      Hierarchical Condition Categories (CMS-HCC) model. There was a significant
      increase in Medicare HHC patient case-mix between the pre-BBA and Prospective
      Payment System (PPS) periods. The increase in the standardized-predicted risk
      score from the Interim Payment System period to PPS was nearly 4 times greater
      for the dual eligibles (Medicare-Medicaid) than for the Medicare-only population.
      This significantly greater rise in the HHC resources required by dual eligibles
      as compared to nonduals could be due to a shift in HHC payers from Medicare only
      to Medicaid rather than be an actual increase in case-mix per se. 

PMID- 24328727
TI  - Beneficial effect of CLOCK gene polymorphism rs1801260 in combination with low
      fat diet on insulin metabolism in the patients with metabolic syndrome.
AB  - Genetic variation at the Circadian Locomotor Output Cycles Kaput (CLOCK) locus
      has been associated with lifestyle-related conditions such as obesity, metabolic
      syndrome (MetS) and cardiovascular diseases. In fact, it has been suggested that
      the disruption of the circadian system may play a causal role in manifestations
      of MetS. The aim of this research was to find out whether habitual consumption of
      a low-fat diet, compared with a Mediterranean diet enriched with olive oil,
      modulates the associations between common CLOCK single nucleotide polymorphisms
      (SNPs) (rs1801260, rs3749474 and rs4580704) and lipid and glucose-related traits
      among MetS patients. Plasma lipid and insulin concentrations, indexes related
      with insulin resistance (homeostasis model assessment of insulin resistance (HOMA
      IR) and quantitative insulin sensitivity check index (QUICKI)) and CLOCK SNPs
      were determined in 475 MetS subjects participating in the CORDIOPREV clinical
      trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary
      intervention (Mediterranean diet (35% fat, 22% monounsaturated fatty acids
      (MUFA)) versus low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet
      interactions between rs1801260 SNP and the dietary pattern for insulin
      concentrations (p = 0.009), HOMA-IR (p = 0.014) and QUICKI (p = 0.028).
      Specifically, after 12 months of low-fat intervention, subjects who were
      homozygous for the major allele (TT) displayed lower plasma insulin
      concentrations (p = 0.032), lower insulin resistance (HOMA-IR; p = 0.027) and
      higher insulin sensitivity (QUICKI; p = 0.024) compared with carriers of the
      minor allele C (TC + CC). In contrast, in the Mediterranean intervention group a
      different trend was observed although no significant differences were found
      between CLOCK genotypes after 12 months of treatment. Our data support the notion
      that a chronic consumption of a healthy diet may play a contributing role in
      triggering glucose metabolism by interacting with the rs1801260 SNP at CLOCK gene
      locus in MetS patients. Due to the complex nature of gene-environment
      interactions, dietary adjustment in subjects with the MetS may require a
      personalized approach.

PMID- 24328728
TI  - Independent associations of exposure to evening light and nocturnal urinary
      melatonin excretion with diabetes in the elderly.
AB  - Circadian misalignment between internal and environmental rhythms dysregulates
      glucose homeostasis because of disruption of the biological clock, and increases
      risk of diabetes. Although exposure to evening light and decreased melatonin
      secretion are both associated with the circadian misalignment, it remains unclear
      whether they are associated with diabetes. In this cross-sectional study on 513
      elderly individuals (mean age, 72.7 years), we measured ambulatory light
      intensity during the 4 h prior to bedtime at 1-min intervals during two
      consecutive days and overnight urinary 6-sulfatoxymelatonin excretion (UME) along
      with glucose metabolism. The median average intensity of evening light exposure
      and UME were 25.4 lux (interquartile range 17.5-37.6) and 6.6 MUg (interquartile
      range 3.9-9.7), respectively. Both log-transformed average intensity of evening
      light exposure and log-transformed UME were significantly associated with
      diabetes in a multivariate logistic regression model adjusted for covariates,
      including gender, body mass index, duration in bed, and night-time light exposure
      [adjusted odds ratio (OR), 1.72; 95% confidence interval (CI), 1.12-2.64; p =
      0.01; and adjusted OR, 0.66; 95% CI, 0.44-0.97; p = 0.04; respectively]. An
      increase in evening light exposure from 17.5 to 37.6 lux (25-75th percentiles)
      was associated with a 51.2% (95% CI, 8.2-111.4%) increase in prevalent diabetes,
      and an increase in UME from 3.9 to 9.7 MUg (25-75th percentiles) was associated
      with a 32.0% (95% CI, 1.9-52.8%) decrease in prevalent diabetes. In conclusion,
      this study in elderly individuals demonstrated that evening light exposure in
      home settings and UME were significantly and independently associated with
      diabetes.

PMID- 24328729
TI  - Like melatonin, agomelatine (S20098) increases the amplitude of oscillations of
      two clock outputs: melatonin and temperature rhythms.
AB  - Depression and biological rhythms disturbances are strongly associated.
      Agomelatine is an antidepressant with melatoninergic MT1-MT2 agonist and
      serotoninergic 5-HT2c antagonist properties. Both melatonin and 5-HT are known to
      modulate circadian rhythmicity controlled by the endogenous clock located in the
      suprachiasmatic nuclei (SCN). The aim of the present study was to compare the
      effect of an acute injection of agomelatine (Ago), melatonin (MLT) or an
      antagonist 5-HT2c (S32006), on the rhythms of two robust clock outputs: the
      pineal MLT secretion and the body temperature rhythm (Tc). Daily endogenous MLT
      profiles were measured using transpineal microdialysis over 4 consecutive days in
      rats maintained on a 12 h light/12 h dark cycle. Simultaneously, Tc was recorded.
      The drugs were injected subcutaneously at three doses (1, 2.5 or 5 mg/kg) at the
      onset of darkness. Both Ago and MLT, at the dose of 2.5 mg/kg, increased the
      amplitude of the peak of MLT secretion and this effect was observed 2 d after
      injection. Moreover, both drugs induced a dose-dependent advance of the rhythm
      onset which resulted in lengthening of the MLT peak. S32006 had no effect on the
      rhythm of MLT. Ago, MLT and S32006 increased the amplitude of the rhythm of Tc.
      These data suggest a central action of Ago, directly on the SCN, via
      melatoninergic receptors responsible for both the increased amplitude of MLT
      rhythm and the phase advance. The increase in the amplitude of the body
      temperature could involve both MLT agonist and/or 5-HT2c antagonist properties of
      Ago.

PMID- 24328730
TI  - Efficient exciton concentrators built from colloidal core/crown CdSe/CdS
      semiconductor nanoplatelets.
AB  - We present the synthesis and the optical properties of a new type of two
      dimensional heterostructure: core/crown CdSe/CdS nanoplatelets. They consist of
      CdSe nanoplatelets that are extended laterally with CdS. Both the CdSe core and
      the CdS crown dimensions can be controlled. Their thickness is controlled at the
      monolayer level. These novel nanoplatelet-based heterostructures have
      spectroscopic properties that can be similar to nanoplatelets or closer to
      quantum dots, depending on the CdSe core lateral size. 

PMID- 24328731
TI  - Uncoupling protein-2 mediates DPP-4 inhibitor-induced restoration of endothelial
      function in hypertension through reducing oxidative stress.
AB  - AIMS: Although uncoupling protein 2 (UCP2) negatively regulates intracellular
      reactive oxygen species (ROS) production and protects vascular function, its
      participation in vascular benefits of drugs used to treat cardiometabolic
      diseases is largely unknown. This study investigated whether UCP2 and associated
      oxidative stress reduction contribute to the improvement of endothelial function
      by a dipeptidyl peptidase-4 inhibitor, sitagliptin, in hypertension. RESULTS:
      Pharmacological inhibition of cyclooxygenase-2 (COX-2) but not COX-1 prevented
      endothelial dysfunction, and ROS scavengers reduced COX-2 mRNA and protein
      expression in spontaneously hypertensive rats (SHR) renal arteries. Angiotensin
      II (Ang II) evoked endothelium-dependent contractions (EDCs) in C57BL/6 and UCP2
      knockout (UCP2KO) mouse aortae. Chronic sitagliptin administration attenuated
      EDCs in SHR arteries and Ang II-infused C57BL/6 mouse aortae and eliminated ROS
      overproduction in SHR arteries, which were reversed by glucagon-like peptide 1
      receptor (GLP-1R) antagonist exendin 9-39, AMP-activated protein kinase
      (AMPK)alpha inhibitor compound C, and UCP2 inhibitor genipin. By contrast,
      sitagliptin unaffected EDCs in Ang II-infused UCP2KO mice. Sitagliptin increased
      AMPKalpha phosphorylation, upregulated UCP2, and downregulated COX-2 expression
      in arteries from SHR and Ang II-infused C57BL/6 mice. Importantly, exendin 9-39,
      compound C, and genipin reversed the inhibitory effect of GLP-1R agonist exendin
      4 on Ang II-stimulated mitochondrial ROS rises in SHR endothelial cells.
      Moreover, exendin-4 improved the endothelial function of renal arteries from SHR
      and hypertensive patients. INNOVATION: We elucidate for the first time that UCP2
      serves as an important signal molecule in endothelial protection conferred by GLP
      1-related agents. UCP2 could be a useful target in treating hypertension-related
      vascular events. CONCLUSIONS: UCP2 inhibits oxidative stress and downregulates
      COX-2 expression through GLP-1/GLP-1R/AMPKalpha cascade.

PMID- 24328733
TI  - Robot-assisted radical prostatectomy of clinical high-risk patients with prostate
      cancer: a controlled study of operative and short-term postoperative events.
AB  - OBJECTIVE: Robot-assisted laparoscopic prostatectomy (RALP) has increasingly
      become a treatment alternative for patients with high-risk prostate cancer. Few
      papers focus on the prevalence of operative and short-term postoperative (<30
      days) adverse events associated with RALP in high-risk patients. The objective of
      this study was to study such events in high-risk patients using intermediate- and
      low-risk patients as contrast groups. MATERIAL AND METHODS: In total, 1076
      patients who underwent RALP at Oslo University Hospital, Radiumhospitalet,
      between the start of 2005 and end of 2010 were studied. Based on the D'Amico
      classification the sample consisted of 374 (35%) high-, 475 (44%) intermediate-
      and 227 (21%) low-risk patients. An index of seven adverse effects was
      dichotomized into zero or any number of adverse effects. RESULTS: The high-risk
      group had significantly longer operation time, more positive surgical margins,
      larger prostate volume and less nerve-sparing than the contrast groups. No
      between-group differences were observed for reoperation, catheter time, bleeding
      volume or transfusions. Significantly more Clavien complications were observed in
      the high-risk than in the low-risk group. A positive adverse effect index score
      was associated with positive margins, no nerve-sparing surgery and no
      preoperative magnetic resonance imaging, and negatively associated with the
      second and third of three 2-year study periods. CONCLUSIONS: High-risk patients
      had a significantly higher risk of some operative and short-term postoperative
      adverse events than the control groups. This was not the case for the seven-items
      adverse event index. This study does not support any restricted attitude towards
      RALP in high-risk patients, except for general surgical contraindications.

PMID- 24328732
TI  - ApoE4 delays dendritic spine formation during neuron development and accelerates
      loss of mature spines in vitro.
AB  - The epsilon4 allele of the gene that encodes apolipoprotein E (APOE4) is the
      greatest genetic risk factor for Alzheimer's disease (AD), while APOE2 reduces AD
      risk, compared to APOE3. The mechanism(s) underlying the effects of APOE on AD
      pathology remains unclear. In vivo, dendritic spine density is lower in APOE4
      targeted replacement (APOE-TR) mice compared with APOE2- and APOE3-TR mice. To
      investigate whether this apoE4-induced decrease in spine density results from
      alterations in the formation or the loss of dendritic spines, the effects of
      neuron age and apoE isoform on the total number and subclasses of spines were
      examined in long-term wild-type neurons co-cultured with glia from APOE2-, APOE3-
      and APOE4-TR mice. Dendritic spine density and maturation were evaluated by
      immunocytochemistry via the presence of drebrin (an actin-binding protein) with
      GluN1 (NMDA receptor subunit) and GluA2 (AMPA receptor subunit) clusters. ApoE
      isoform effects were analyzed via a method previously established that identifies
      phases of spine formation (day-in-vitro, DIV10-18), maintenance (DIV18-21) and
      loss (DIV21-26). In the formation phase, apoE4 delayed total spine formation.
      During the maintenance phase, the density of GluN1+GluA2 spines did not change
      with apoE2, while the density of these spines decreased with apoE4 compared to
      apoE3, primarily due to the loss of GluA2 in spines. During the loss phase, total
      spine density was lower in neurons with apoE4 compared to apoE3. Thus, apoE4
      delays total spine formation and may induce early synaptic dysfunction via
      impaired regulation of GluA2 in spines. 

PMID- 24328734
TI  - Minimally invasive transnasal medial maxillectomy for treatment of maxillary
      sinus and orbital pathologies.
AB  - CONCLUSION: Minimally invasive transnasal medial maxillectomy with preservation
      of the nasolacrimal duct may provide an alternative method for surgical treatment
      of selected maxillary sinus and inferior orbit pathology if more extensive
      endonasal or external approach procedures are to be avoided. OBJECTIVES: To
      present a modification of the transnasal endoscopic approach to the maxillary
      sinus leading through its medial wall, anteriorly to the nasolacrimal duct that
      considerably improves access to the antero-inferior part of the maxillary sinus
      and entire orbital floor. To discuss indications for the procedure along with
      surgical outcome after at least 12 months of follow-up. METHODS: A total of 22
      selected patients with extensive/refractory inflammatory maxillary sinus disease
      that could not be cleared completely through middle meatal antrostomy or
      pathologies of the inferior orbit that required uncompromised access to the
      orbital floor were operated with this method. The effectiveness of the treatment
      was evaluated through clinical symptomatology and endoscopic examination to
      confirm eradication of the disease. RESULTS: The presented method allowed for
      good overall symptom control and eradication of disease confirmed endoscopically
      in about 90% of cases with an inflammatory type of disease. The visualized reach
      within the maxillary sinus with commercially available endoscopic instruments was
      conspicuously improved as compared with middle meatal antrostomy.

PMID- 24328735
TI  - Optimizing delivery and expression of designer nucleases for genome engineering.
AB  - Genome engineering can be accomplished by designer nucleases. They are
      specifically designed to cleave double-stranded DNA at the desired target locus.
      This double-strand break subsequently engages the DNA repair pathway through
      nonhomologous end-joining (NHEJ), resulting in either gene disruption or gene
      repair. Alternatively, the presence of homologous donor DNA allows for targeted
      integration of this exogenous donor DNA in this target locus through homology
      directed DNA repair. The key bottleneck in genome engineering relates to the
      delivery and expression of the designer nucleases. One of the most attractive
      vector platforms for genome engineering is based on integration-defective
      lentiviral vectors (IDLVs). The intrinsic episomal nature of IDLVs is well suited
      to ensure transient expression of designer nucleases and minimize potential risks
      associated with their sustained expression. Unfortunately, their expression is
      compromised because of epigenetic silencing that interferes with the
      transcriptional competence of IDLVs. In this issue, Pelascini and colleagues now
      showed that this bottleneck could be overcome by interfering with chromatin
      remodeling using histone deacetylase (HDAC) inhibitors. HDAC inhibition restored
      expression of designer nucleases from IDLVs and rescued their ability to achieve
      efficient targeted gene disruption by NHEJ comparable with that achieved with
      bona fide integrating lentiviral vectors. This study has implications for the ex
      vivo use of IDLVs for gene repair and gene targeting.

PMID- 24328737
TI  - Improving productivity of modern-day drug discovery.
AB  - The pharmaceutical industry is confronted by increasing costs of clinical
      development and diminishing productivity. The most challenging aspect of drug
      development has been the failure of therapeutics in expensive Phase II or III
      trials, and this is most commonly due to lack of efficacy. More can be done
      during the drug discovery phase to optimize efficacy-testing in animal models by
      expending resources to explore the congruence of the animal model with the human
      disease. Historically, relatively little attention has been paid to validation of
      these models, but access to molecular mRNA and genetic profiling offers a new
      lens through which the similarity of these disease models to human diseases can
      be examined and their utility for exploring therapeutic efficacy can be
      optimized. Exploring congruent experimental end points in clinical and
      preclinical experiments will also increase confidence of success in late phase
      clinical development. The expense of this investment is trivial compared to the
      costs of a failed clinical trial, more than justifying this endeavor. 

PMID- 24328736
TI  - The bronchiectasis severity index. An international derivation and validation
      study.
AB  - RATIONALE: There are no risk stratification tools for morbidity and mortality in
      bronchiectasis. Identifying patients at risk of exacerbations, hospital
      admissions, and mortality is vital for future research. OBJECTIVES: This study
      describes the derivation and validation of the Bronchiectasis Severity Index
      (BSI). METHODS: Derivation of the BSI used data from a prospective cohort study
      (Edinburgh, UK, 2008-2012) enrolling 608 patients. Cox proportional hazard
      regression was used to identify independent predictors of mortality and
      hospitalization over 4-year follow-up. The score was validated in independent
      cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253); Monza, Italy (n =
      105); and Newcastle, UK (n = 126). MEASUREMENTS AND MAIN RESULTS: Independent
      predictors of future hospitalization were prior hospital admissions, Medical
      Research Council dyspnea score greater than or equal to 4, FEV1 < 30% predicted,
      Pseudomonas aeruginosa colonization, colonization with other pathogenic
      organisms, and three or more lobes involved on high-resolution computed
      tomography. Independent predictors of mortality were older age, low FEV1, lower
      body mass index, prior hospitalization, and three or more exacerbations in the
      year before the study. The derived BSI predicted mortality and hospitalization:
      area under the receiver operator characteristic curve (AUC) 0.80 (95% confidence
      interval, 0.74-0.86) for mortality and AUC 0.88 (95% confidence interval, 0.84
      0.91) for hospitalization, respectively. There was a clear difference in
      exacerbation frequency and quality of life using the St. George's Respiratory
      Questionnaire between patients classified as low, intermediate, and high risk by
      the score (P < 0.0001 for all comparisons). In the validation cohorts, the AUC
      for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88.
      CONCLUSIONS: The BSI is a useful clinical predictive tool that identifies
      patients at risk of future mortality, hospitalization, and exacerbations across
      healthcare systems.

PMID- 24328738
TI  - Monitoring changes in heart rate, as an indicator of the cardiovascular autonomic
      nervous function, among patients at the sub-acute phase post-brain damage during
      a physiotherapy session: a preliminary investigation.
AB  - OBJECTIVES: To assess cardiovascular autonomic nervous system function of
      patients post-brain-injury in the sub-acute phase during a physiotherapy session
      (PTS). PARTICIPANTS: Fourteen patients post-ischaemic stroke and 11 post-severe
      traumatic brain injuries. INTERVENTION: Continuous electrocardiogram recording at
      rest, during active cycling and during routine PTS. MAIN OUTCOME MEASURE: Heart
      rate (HR) and Heart rate variability (HRV) parameters included the standard
      deviation of all R-R intervals (SDNN), the square root of the mean squared
      differences of successive differences (RMSSD), the Low-frequency (LF) power, High
      frequency (HF) power and the LF/HF ratio. RESULTS: The median HR at rest was 76
      bpm (interquartile range 61-81). Significant increments were noted during
      activities; median HR during cycling was 93 bpm, during the most intense activity
      91 bpm (p-value < 0.001). A significant decline in HRV parameters' median values
      during cycling and PTS was observed only among patients post-stroke. CONCLUSIONS:
      Among patients post-brain injury, HR increased significantly during PTS in
      different activities and varied positions; therefore, therapists should be aware
      and monitor HR frequently during training. In addition, HRV values were low at
      rest and did not respond to activity among patients post-TBI, compared with
      higher values at rest and some response among patients post-stroke. This may
      indicate that autonomic impairment post-brain insult is more likely a consequence
      of central nervous system damage and less likely a result of pre-event
      cardiovascular illness.

PMID- 24328739
TI  - Multi-specific monoclonal antibody MsMab-2 recognizes IDH1-R132L and IDH2-R172M
      mutations.
AB  - Mutations of isocitrate dehydrogenase 1/2 (IDH1/2) produce oncometabolite R(-)-2
      hydroxyglutarate in several tumors. Arginine 132 (R132) of IDH1 and arginine 172
      (R172) of IDH2 are functionally important residues. Although MsMab-1 monoclonal
      antibody (MAb), which is multi-specific for mutated IDH1/2, has been established,
      MsMab-1 does not react with all IDH1/2 mutations. Herein, we immunized rats with
      IDH1-R132L peptide, and screened IDH1-R132L-reactive/IDH1-wild-type non-reactive
      MAbs in enzyme-linked immunosorbent assay. Unexpectedly, the newly established
      MsMab-2 MAb recognized not only IDH1-R132L but also IDH2-R172M in Western blot
      analyses, neither of which was detected by MsMab-1. Taken together, the
      combination of MsMab-1 and MsMab-2 could be useful in diagnosis of mutated IDH1/2
      bearing tumors. 

PMID- 24328740
TI  - Monoclonal antibodies against NS4B protein of japanese encephalitis virus.
AB  - Japanese encephalitis (JE) is one of the most prevalent global viral encephalitis
      viruses. The functions of JEV (virus) NS4B protein are still under investigation.
      In our study, NS4B was expressed in Escherichia coli and purified by dialysis.
      Two clones of monoclonal antibodies (MAbs 1B1 and 1C3) against NS4B protein were
      generated and their characterizations were investigated. IFA, Western blot, and
      ELISA results showed that the MAbs were specific against JEV NS4B protein. The
      epitope of the MAbs was further identified using pairs of synthesized overlapping
      peptides. These MAbs may provide valuable tools for further exploration of the
      functions of NS4B and the pathogenesis of Japanese encephalitis virus. 

PMID- 24328741
TI  - Monoclonal antibodies for diagnosis of enterovirus 71.
AB  - Enterovirus 71 (EV71), one of the major causative agents of hand, foot, and mouth
      disease (HFMD), is now recognized as an emerging neurotropic virus in Asia and
      may cause severe neurologic complications and mortalities. Laboratory diagnosis
      of EV71 infection must be efficient and accurate, which could be accomplished by
      various immunoassays. In this study we use a live EV71 isolate, Tainan/4643/98,
      with genotype C2 as an immunogen to sensitize BALB/c (H-2(d)) mice and then
      generate the EV71-specific murine monoclonal antibodies. Five hybridoma clones
      were established and their monoclonal antibodies were characterized. All five
      clones are applicable in immunofluorescence staining but with different
      sensitivities-that is, MAbs 22, 24, and 27 were sensitive in IFA detection, and
      MAbs 22 and 24 were also confirmed in flow cytometry. None of these cross-reacted
      with coxsackievirus A16 (CVA16) or Echovirus type 6 (ECHO6), but each varied in
      binding to different EV71 subgenogroups (B1, B4, B5, C2, and C4). Western blot
      analysis revealed that all of these MAbs reacted with EV71 VP1 capsid proteins,
      and in addition MAbs 22 and 24 exhibited potent neutralizing activities against
      EV71 and protected cells from infection. Further, mapping the epitopes for each
      MAb revealed that only MAb 27 showed positive for the linear epitope
      DVIESSIGDSVSRAL, which was located at the N-terminus (a.a. 6-20) of EV71 VP1 and
      highly conserved among all EV71 subgenotypes. Thus, these MAbs may provide
      valuable tools for the laboratory diagnosis of EV71 infection and for vaccine
      development. 

PMID- 24328742
TI  - Murine b7-h3 is a co-stimulatory molecule for T cell activation.
AB  - The B7 family member B7-H3 (CD276) plays a key role during an immune response but
      its function remains controversial. In this study, we found that murine B7-H3 up
      regulated the proliferation and cytokine production of T cells. Our study
      suggested that there was no interaction of murine B7-H3 with a triggering
      receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2). Further
      studies demonstrated that mouse B7-H3 specifically bound to T cells and its
      receptor was not murine TLT-2. Moreover, murine B7-H3 was a positive co
      stimulatory molecule in the regulation of T cell-mediated immune responses. 

PMID- 24328743
TI  - Prevalence of human papillomavirus genotypes associated with cervical and breast
      cancers in iran.
AB  - Cancer is a multi-step disease, and infection with a DNA virus could play a role
      in one or more of the steps in this pathogenic process. High-risk human
      papillomaviruses (HPV) are the causative agent of several cancers. In this study,
      we determined the prevalence and genotype distribution of HPV infection among
      Iranian patients with cervix lesions (CL) and breast cancer (BC). The study group
      consisted of postoperative tissues from patients diagnosed with cervix lesions
      and breast cancer. We analyzed 250 formalin-fixed, paraffin-embedded tissue
      blocks from 100 cervix lesions and 150 breast cancer samples. Verification of
      each cancer reported in a relative was sought through the pathology reports of
      the hospital records. Cervix lesions were collected from 100 patients with
      squamous metaplasia (SM, n=50), cervical intraepithelial neoplasia (CINI, n=18,
      CINII or III, n=8), and cervical carcinoma (CC, n=24). In this study we evaluated
      the prevalence of HPV by multiplex PCR in cervix lesions and breast cancer. For
      paraffin-embedded tissues, DNA extracted by the simple boiling method yielded
      higher proportions of successful gene amplification (99%) for b-actin gene.
      Overall prevalence of HPV infection was 6% in the SM group, 34.61% in the CIN
      group, 75% in the CC group, and 34.66% in the BC group. Furthermore, MY09/11
      consensus PCR failed to detect 44 (55.69%) of all HPV infections and
      interestingly, the predominant genotype detected in all cancers was the oncogenic
      variant HPV16/18; about 34% of women aged 24 to 54 were infected with at least
      one type of HPV. Our results demonstrate that DNA derived from archival tissues
      that archived for less than 8 years could be used successfully for HPV genotyping
      by multiplex PCR. Infection with HPV was prevalent among Iranian women with CC
      and BC. The results indicate a likely causal role for high-risk HPV in CC and BC,
      and also offer the possibility of primary prevention of these cancers by
      vaccination against HPV in Iran. 

PMID- 24328745
TI  - Protein L: a robust enzyme-conjugated molecule for detection of humanized single
      chain antibodies.
AB  - The current study was aimed at introducing an efficient enzyme-conjugated
      molecule for use in the detection of humanized single chain antibodies. Because
      they are composite in their variable domain sequences and also devoid of constant
      domains, humanized single chain antibodies require a suitable secondary enzyme
      conjugated antibody (more precisely enzyme-conjugated protein molecule) to be
      efficiently recognized and detected in ELISA, dot blot, and other detection
      tests, guaranteeing a more precise evaluation of their quantity, affinity, and
      other features. In the current study we examined the ability of three HRP
      conjugated protein molecules including protein L, anti-human IgG antibody, and
      anti-mouse IgG antibody in the detection of three humanized single chain
      antibodies (anti-CD20, anti-EGFRvIII, and anti-EGFR) in ELISA and dot blot tests.
      The results signify the HRP-conjugated protein L as the most efficient molecule
      for detecting humanized single chain antibody. 

PMID- 24328744
TI  - Expression of calcitonin gene-related peptide in rat pulp and periodontal tissues
      by indirect immunofluorescence method.
AB  - The aim of this study was to investigate the expression of nerve fibers
      immunoreactive to calcitonin gene-related peptide (CGRP) in pulp and periodontal
      tissues of rats. Male Sprague-Dawley rats, aged 6 weeks, were sacrificed, and the
      jaws were excised, demineralized, and processed for indirect immunofluorescence
      staining. A considerably higher density of nerve fibers immunoreactive to CGRP
      was found in the dental pulp and gingiva than in periodontal ligament. The
      majority of pulpal CGRP immunopositive fibers that were located followed blood
      vessels parallel to the long axis of the root. A subodontoblastic network of
      fibers IR to CGRP was found in the coronal pulp in rat molars. In the
      periodontium, CGRP immunopositive fibers were mainly located in the periapical
      area and close to the alveolar bone. Gingiva was also well supplied with CGRP-IR
      nerves. 

PMID- 24328746
TI  - Production and characterization of monoclonal antibodies against nucleoprotein of
      avian influenza virus.
AB  - The present study was carried out with an aim to develop anti-nucleoprotein (anti
      NP) monoclonal antibodies (MAbs) for use in immunodiagnostic testing for
      detection of avian influenza virus (AIV) antigen or antibodies. The NP gene of
      AIV, cloned in pET vector, was expressed in Escherichia coli BL 21 strain to
      produce a 6x-His tagged recombinant NP (rNP) antigen of ~61 kDa molecular weight
      as soluble fraction. The rNP antigen was detected in soluble fraction of
      bacterial cell lysate with anti-His HRPO conjugate and reacted with the reference
      AIV antibody positive serum in immunoblotting. The rNP was used to immunize
      BALB/c mice to produce hybridoma secreting anti-NP MAbs. Out of 11 anti-NP MAbs
      produced, 8D2-H5, 8D2-H9, and 6D11-A7 were of IgM isotype and 5D10-C9 and 5D10
      F11 were of IgG2b type, while 3F3-D2, 7D2-C9, 7D2-G7, and 7D2-G8 were of IgG1
      isotype. The MAbs 3F3-D2 and 7D2-G8 showed high intensity positive reaction with
      rNP and a low intensity reaction with H5N1 virus in Western blot analysis. The
      anti-NP MAbs produced in the present work may be valuable in developing a
      competitive ELISA or immunochromatographic strip test-based assays for the rapid
      diagnosis of avian influenza. 

PMID- 24328747
TI  - A polyclonal antibody against recombinant bovine haptoglobin expressed in
      Escherichia coli.
AB  - The nucleotide sequence of the predicted immunodominant region of bovine
      haptoglobin (pirBoHp), without the signal peptide sequence, was synthesized based
      on the codon usage bias of Escherichia coli. The synthesized pirBoHp gene was
      cloned into the prokaryotic expression vector pET-32a (+), which contains a His
      tag. The recombinant pirBoHp protein was successfully expressed in E. coli BL21
      (DE3) cells. Western blot analysis showed that the purified recombinant pirBoHp
      protein could be recognized by an anti-His-tag monoclonal antibody. Further
      investigations indicated that a polyclonal antibody against the recombinant
      pirBoHp protein could recognize the alpha and beta chains of native bovine
      haptoglobin in a pooled plasma sample from dairy cattle suffering from foot rot. 

PMID- 24328748
TI  - Homophilic peptide inhibits growth of malignant murine and human B cells.
AB  - A homophilic peptide from the T15 plasmacytoma inhibits growth of murine and
      human B cell tumors. This finding confirms the hypothesis that B cell
      malignancies are driven by a self-binding epitope in the B cell receoptor (BCR)
      proposed as the pathogenesis of chronic lymphocytic leukemia (CLL). 

PMID- 24328749
TI  - Monoclonal antibody RcMab-1 against IDH1.

PMID- 24328750
TI  - Monoclonal antibody MsMab-1 against mutated IDH1 and IDH2.

PMID- 24328751
TI  - Monoclonal antibody MsMab-2 against mutated IDH1 and IDH2.

PMID- 24328752
TI  - Monoclonal antibody NZ-1 against PA tag.

PMID- 24328753
TI  - The relation between prepregnancy sexuality and sexual function during pregnancy
      and the postpartum period: a prospective study.
AB  - This study examined the relation between sexual functions of women in
      prepregnancy (before conception) and during pregnancy and the postpartum period.
      This study was conducted on 59 healthy pregnant women. Participants were followed
      from the eighth week of gestation to 6 months after delivery. Sexual function
      during pregnancy and the postpartum period was shown to have a significant linear
      correlation with prepregnancy sexuality. There was no relation between pregnancy
      and postpartum sexuality. All of the participants who had prepregnancy sexual
      dysfunction continued to experience it during pregnancy, and the majority of them
      had a significant level of sexual dysfunction in the postpartum period. Our
      results showed that prepregnancy sexuality plays an important role in maintaining
      sexuality during pregnancy and the postpartum period. 

PMID- 24328754
TI  - Arylthio-metal exchange of alpha-arylthioalkanenitriles.
AB  - The addition of BuLi, Bu3MgLi, Et2ZnBuLi, or Me2CuLi to alpha
      arylthioalkanenitriles triggers an arylthio-metal exchange. NMR spectroscopic
      analyses implicate organometallic attack on sulfur forming a three-coordinate
      sulfidate as the key intermediate. Electrophilic trapping affords tertiary and
      quaternary nitriles in high yield. The method addresses the challenge of
      improving the functional group tolerance and preventing polyalkylations. 

PMID- 24328755
TI  - Induction of micronuclei and nuclear lesions in Channa punctatus following
      exposure to carbosulfan, glyphosate and atrazine.
AB  - The genotoxic effects of commonly used agricultural pesticides viz., carbosulfan,
      glyphosate, and atrazine, were evaluated in Channa punctatus (Pisces,
      Perciformes) using micronucleus (MN) test and induction of nuclear lesions (NL).
      The 96 h LC50 value were estimated by probit analysis as 0.27, 32.0 and 42.0 mg
      L(-1), respectively, for carbosulfan, glyphosate, and atrazine using semi-static
      bioassays. Based on these values, three sublethal test concentrations of
      carbosulfan (0.07, 0.13, 0.20 mg L(-1)), glyphosate (8.1, 16.3, 24.4 mg L(-1))
      and atrazine (10.6, 21.2, 31.8 mg L(-1)) corresponding to 1/4, 1/2 and 3/4 of the
      LC50 of the pesticides respectively, were selected for exposure for 96 h.
      Peripheral blood samplings were taken at intervals of 24 h for assessment of MN
      and NL frequencies. Considerably higher genotoxic damage was induced by
      carbosulfan as compared to glyphosate and atrazine. There were significant
      effects (p < 0.01) of concentrations in all the treated groups. The induction of
      MN and NL was highest at 96 h pesticide exposure at all test concentrations. The
      nuclear abnormalities recorded in this study, such as blebbed-, lobed-, notched-
      and bi-nuclei, other than micronuclei, are indicators of genotoxic damage.

PMID- 24328756
TI  - Towards a consensus on a hearing preservation classification system.
AB  - CONCLUSION: The comprehensive Hearing Preservation classification system
      presented in this paper is suitable for use for all cochlear implant users with
      measurable pre-operative residual hearing. If adopted as a universal reporting
      standard, as it was designed to be, it should prove highly beneficial by enabling
      future studies to quickly and easily compare the results of previous studies and
      meta-analyze their data. OBJECTIVES: To develop a comprehensive Hearing
      Preservation classification system suitable for use for all cochlear implant
      users with measurable pre-operative residual hearing. METHODS: The HEARRING group
      discussed and reviewed a number of different propositions of a HP classification
      systems and reviewed critical appraisals to develop a qualitative system in
      accordance with the prerequisites. RESULTS: The Hearing Preservation
      Classification System proposed herein fulfills the following necessary criteria:
      1) classification is independent from users' initial hearing, 2) it is
      appropriate for all cochlear implant users with measurable pre-operative residual
      hearing, 3) it covers the whole range of pure tone average from 0 to 120 dB; 4)
      it is easy to use and easy to understand.

PMID- 24328758
TI  - Homosexuality in Turkey: strategies for managing heterosexism.
AB  - The goal of this study was to identify the strategies used by young homosexuals
      to manage their sexual minority status in Turkey. In-depth interviews were
      conducted with 15 self-identified homosexual university students. The data on the
      strategies employed by homosexuals suggested a categorization of these strategies
      into four interrelated areas: strategies employed in the process of self
      acceptance; strategies to manage sexual stigma and prejudice; strategies specific
      to the coming-out process; and the strategies used while openly expressing their
      sexual identities. 

PMID- 24328759
TI  - Effect of machined interfacet allograft spacers on cervical foraminal height and
      area.
AB  - OBJECT: Iatrogenic foraminal stenosis is a well-known complication in cervical
      spine surgery. Machined interfacet allograft spacers can provide a large surface
      area, which ensures solid support, and could potentially increase foraminal
      space. The authors tested the hypothesis that machined interfacet allograft
      spacers increase cervical foraminal height and area. METHODS: The C4-5, C5-6, and
      C6-7 facets of 4 fresh adult cadavers were exposed, and the cartilage was removed
      from each facet using customized rasps. Machined allograft spacers were tamped
      into the joints. The spines were scanned with the O-arm surgical imaging system
      before and after placement of the spacers. Two individuals independently measured
      foraminal height and area on obliquely angled sagittal images. RESULTS: Foraminal
      height and area were significantly greater following placement of the machined
      interfacet spacers at all levels. The Pearson correlation between the 2
      radiographic reviewers was very strong (r = 0.971, p = 0.0001), as was the
      intraclass correlation coefficient (ICC = 0.907, p = 0.0001). The average
      increase in foraminal height was 1.38 mm. The average increase in foraminal area
      was 18.4% (0.097 cm(2)) [corrected]. CONCLUSIONS: Modest distraction of the
      facets using machined interfacet allograft spacers can increase foraminal height
      and area and therefore indirectly decompress the exiting nerve roots. This
      technique can be useful in treating primary foraminal stenosis and also for
      preventing iatrogenic foraminal stenosis that may occur when the initially
      nonlordotic spine is placed into lordosis either with repositioning after central
      canal decompression or with correction using instrumentation. These grafts may be
      a useful adjunct to the surgical treatment of cervical spine disease.

PMID- 24328757
TI  - Neurovascular regulation in the ischemic brain.
AB  - SIGNIFICANCE: The brain has high energetic requirements and is therefore highly
      dependent on adequate cerebral blood supply. To compensate for dangerous
      fluctuations in cerebral perfusion, the circulation of the brain has evolved
      intrinsic safeguarding measures. RECENT ADVANCES AND CRITICAL ISSUES: The
      vascular network of the brain incorporates a high degree of redundancy, allowing
      the redirection and redistribution of blood flow in the event of vascular
      occlusion. Furthermore, active responses such as cerebral autoregulation, which
      acts to maintain constant cerebral blood flow in response to changing blood
      pressure, and functional hyperemia, which couples blood supply with synaptic
      activity, allow the brain to maintain adequate cerebral perfusion in the face of
      varying supply or demand. In the presence of stroke risk factors, such as
      hypertension and diabetes, these protective processes are impaired and the
      susceptibility of the brain to ischemic injury is increased. One potential
      mechanism for the increased injury is that collateral flow arising from the
      normally perfused brain and supplying blood flow to the ischemic region is
      suppressed, resulting in more severe ischemia. FUTURE DIRECTIONS: Approaches to
      support collateral flow may ameliorate the outcome of focal cerebral ischemia by
      rescuing cerebral perfusion in potentially viable regions of the ischemic
      territory.

PMID- 24328760
TI  - Serial endovascular embolization as stand-alone treatment of a sacral aneurysmal
      bone cyst.
AB  - Aneurysmal bone cysts (ABCs) are destructive cystic lesions of the bone and are
      common in children. They are expansile in nature and, therefore, may become
      symptomatic. These have traditionally been treated surgically; but recently,
      endovascular embolization has shown promise as a stand-alone therapy. The authors
      describe a case of an ABC highlighting the effectiveness and efficiency of
      endovascular treatment. A 16-year-old boy was referred for a 4-month history of
      radiating back pain and urinary hesitancy. Findings from his neurological
      examination were normal, but he had problems ambulating because of pain. Magnetic
      resonance imaging and CT scanning showed a cystic mass in the sacrum; a biopsy
      was performed and diagnosis of ABC was confirmed. Treatment options were then
      discussed with the family. The patient underwent 2 endovascular embolizations in
      approximately 1 month: Onyx 18 was involved in the first session, and N-butyl
      cyanoacrylate glue was used in the second session. After the first treatment, the
      patient experienced a dramatic decrease in pain and concomitant improvement in
      function. The patient went from being mildly symptomatic after the first
      treatment to completely asymptomatic after the second treatment. Clinical and
      radiographic follow-up obtained at 2, 6, and 18 months after initial treatment
      revealed the patient to be asymptomatic with progressive ossification.
      Endovascular treatment can be effective in treating symptomatic cases of ABC in
      which surgery would carry significant risk. Selective arterial embolization can
      promote sclerosis and result in an immediate and significant decrease in pain. 

PMID- 24328761
TI  - Combining internal fixation with vertebroplasty.

PMID- 24328762
TI  - Improved magnetic resonance myelography of the lumbar spine using image fusion
      and volumetry.
AB  - OBJECT: The goal of this study was to investigate the usefulness and diagnostic
      potential of an improved MR myelography approach using a dedicated, heavily T2
      weighted, 3D MRI sequence in combination with image fusion. A further aim was to
      compare dural areas and volumes of normal and pathological altered lumbar spine
      levels, and accuracy in the assessment of the stenoses, with those obtained by
      postmyelographic CT. METHODS: Fifty patients underwent myelography,
      postmyelographic CT, and the improved MR myelography approach using a dedicated,
      heavily T2-weighted, 3D MRI sequence and image fusion. Dural cross-sectional
      areas and volumes for normal lumbar levels and levels with stenosis were
      calculated for postmyelographic CT and MR myelography data. The significant
      differences and Pearson correlations between dural cross-sectional areas and
      volumes from L1-2 to L5-S1 of postmyelographic CT and MR myelography were
      analyzed. The 99% CIs for normal and stenotic levels in patients with
      claudication distances less than 100 meters were calculated. RESULTS: For both
      dural areas and volumes in normal lumbar levels, the authors found no significant
      differences and strong correlations between postmyelographic CT and MR
      myelography. For the lower lumbar levels (L4-5 and L5-S1) they found
      significantly larger dural areas on MR myelography compared with postmyelographic
      CT, but not for the upper levels (L2-3 and L3-4). Dural volume analysis revealed
      significantly larger volumes for MR myelography at all 4 lumbar levels with
      stenoses in the cohort (L2-3 to L5-S1). Complete separation with no overlap was
      found between the 99% CIs for normal levels and stenotic levels. CONCLUSIONS:
      Differences in dural areas and volumes in this study may have been caused by the
      fact that in the case of a severely compressed thecal sac, the viscosity of the
      intrathecally applied contrast agent is too high in the framework of myelography.
      The gravitationally dependent component is thus too low to achieve sufficient
      fluid contrast. An optimized MR myelography approach-a dedicated 3D MR
      myelography sequence with high spatial resolution in combination with image
      fusion-is required to achieve a more reliable diagnosis of lumbar spine stenoses,
      especially with severe compression, compared with postmyelographic CT. This MR
      myelography approach may be helpful in preventing overestimation of lumbar spine
      stenoses. The upper limits of 99% CIs for stenotic levels can be interpreted as
      an indication for surgical treatment. However, further studies that include
      postoperative outcomes are required.

PMID- 24328764
TI  - A nanomechanical Fredkin gate.
AB  - Irreversible logic operations inevitably discard information, setting fundamental
      limitations on the flexibility and the efficiency of modern computation. To
      circumvent the limit imposed by the von Neumann-Landauer (VNL) principle, an
      important objective is the development of reversible logic gates, as proposed by
      Fredkin, Toffoli, Wilczek, Feynman, and others. Here, we present a novel
      nanomechanical logic architecture for implementing a Fredkin gate, a universal
      logic gate from which any reversible computation can be built. In addition to
      verifying the truth table, we demonstrate operation of the device as an AND, OR,
      NOT, and FANOUT gate. Excluding losses due to resonator dissipation and
      transduction, which will require significant improvement in order to minimize the
      overall energy cost, our device requires an energy of order 10(4) kT per logic
      operation, similar in magnitude to state-of-the-art transistor-based
      technologies. Ultimately, reversible nanomechanical logic gates could play a
      crucial role in developing highly efficient reversible computers, with
      implications for efficient error correction and quantum computing. 

PMID- 24328766
TI  - Cascade effects in critical care medicine: a call for practice changes.

PMID- 24328763
TI  - Mitochondrial fusion and fission proteins: novel therapeutic targets for
      combating cardiovascular disease.
AB  - Mitochondria are no longer considered to be solely the static powerhouses of the
      cell. While they are undoubtedly essential to sustaining life and meeting the
      energy requirements of the cell through oxidative phosphorylation, they are now
      regarded as highly dynamic organelles with multiple functions, playing key roles
      in cell survival and death. In this review, we discuss the emerging role of
      mitochondrial fusion and fission proteins, as novel therapeutic targets for
      treating a wide range of cardiovascular diseases.

PMID- 24328767
TI  - beta-Adrenoceptor genotype and bronchoprotective subsensitivity with long-acting
      beta-agonists in asthma.

PMID- 24328768
TI  - Large chronic obstructive pulmonary disease cohorts: advantages and caution in
      biomarker discovery/validation.

PMID- 24328769
TI  - Volutrauma and regional ventilation revisited.

PMID- 24328770
TI  - Is all on the level? Hemodynamics during supine versus prone ventilation.

PMID- 24328771
TI  - Trouble from the start: airway structural anomalies present at birth in the
      cystic fibrosis piglet.

PMID- 24328772
TI  - Idiopathic pulmonary fibrosis: time to get personal?

PMID- 24328773
TI  - Sleep apnea and subclinical myocardial injury: where do we stand?

PMID- 24328774
TI  - Regional distribution of air trapping in chronic obstructive pulmonary disease.

PMID- 24328775
TI  - Role of primary necrosis/lysis of submucosal eosinophils in obese individuals
      with asthma.

PMID- 24328776
TI  - Reply: Role of primary necrosis/lysis of submucosal eosinophils in obese
      individuals with asthma.

PMID- 24328777
TI  - Diet and exercise-induced bronchoconstriction.

PMID- 24328778
TI  - Chlorophyllin-stained macrophages as markers of pulmonary aspiration.

PMID- 24328779
TI  - miR-26a linked to pulmonary hypertension by global assessment of circulating
      extracellular microRNAs.

PMID- 24328780
TI  - Marked epithelial cell pathology and leukocyte paucity in persistently
      symptomatic severe asthma.

PMID- 24328782
TI  - Tophus causing bronchial obstruction.

PMID- 24328783
TI  - Light at night, melatonin and breast cancer.

PMID- 24328784
TI  - Preferences for psychological therapy in psychosis: trial participation, mode of
      treatment, and willingness to be randomised.
AB  - BACKGROUND: Psychological therapies for psychosis are well evidenced; however,
      service user preferences for psychological treatment and trial participation have
      been little researched. AIMS: To investigate preferences for psychological
      treatments for psychosis and trial participation decisions within a sample of
      people with experience of psychosis. METHOD: Hypothetical preferences were
      assessed in 90 individuals diagnosed with non-affective psychosis: (a)
      willingness/unwillingness to participate in a psychological therapy trial; (b)
      willingness/unwillingness to be randomised to treatment condition; (c) preference
      for mode of therapy; (d) reasons for preferences; (e) socio-demographic and
      clinical characteristics associated with preferences. RESULTS: Most participants
      reported willingness to participate in a therapy trial and preferred not to be
      randomly allocated. Reasons for preferences were diverse, and preferences were
      not associated with socio-demographic or clinical variables. CONCLUSIONS: The
      need for treatment choice in services for psychosis and further research in this
      area has been highlighted.

PMID- 24328785
TI  - Cardiovascular variability before and after delivery: recovery from arterial
      stiffness in women with preeclampsia 4 days post partum.
AB  - OBJECTIVE: We studied the short-term response of autonomic control to delivery in
      normal pregnancies and pregnancies with preeclampsia (PE). METHODS: Fourteen
      healthy pregnant women and 13 women with PE were monitored within four days
      before and four days after delivery and compared to values of 14 non-pregnant
      women as controls using high-resolution electrocardiogram and noninvasive
      continuous blood pressure monitoring. RESULTS: In PE, blood pressure remained
      elevated four days postpartum, but markers for arterial stiffness normalized. In
      contrast, none of heart rate variability and baroreflex sensitivity parameters,
      altered due to either pregnancy or disease, were normalized 96 h after delivery.
      CONCLUSION: Four days after delivery, the maternal cardiovascular system is still
      strongly affected by pregnancy independent of the health status.

PMID- 24328786
TI  - Relationship factors and quality among mixed-orientation couples.
AB  - Mixed-orientation couples are defined as a heterosexual couple in which 1 partner
      experiences same-sex attraction and the other does not. Despite the fact that
      there is a sizable number of mixed-orientation couples in the U.S. adult
      population, few researchers have studied this population, and thus, there is
      limited understanding of these relationships. The authors examined the degree to
      which relationship commitment, partner-focused forgivingness, and marital values
      were associated with relationship quality, and how these variables predicted
      relationship quality. The total sample (N = 265) consisted of 2 independent
      samples-105 sexual minorities (i.e., the spouse who experiences same-sex
      attraction) and 160 heterosexual spouses. The data were not dyadic. Together,
      commitment, partner-focused forgivingness, and marital values accounted for
      roughly 43% of the variance in relationship quality. Relationship commitment was
      found to be the largest single predictor of relationship quality, followed by
      partner-focused forgivingness. Research and clinical implications are discussed.
      This study significantly adds to the current research base by quantitatively
      measuring various variables in these relationships, as well as expanding our
      understanding of relationship quality in mixed-orientation couples and factors
      that may play a role. 

PMID- 24328788
TI  - Trypanosoma caninum, a new parasite described in dogs in Brazil: aspects of
      natural infection.
AB  - Trypanosoma caninum constitutes the most recent trypanosomatid species infecting
      dogs in Brazil. Due to the limited data available about this parasite, this study
      aims to disclose clinical and laboratory findings from 14 dogs naturally
      infected. The dogs were diagnosed during a cross-sectional survey in Cuiaba (Mato
      Grosso, Brazil) and followed up at an interval of 3, 6, and 12 mo in order to
      evaluate the clinical evolution and to investigate the parasite, the DNA, or both
      in different biological samples (intact skin, cutaneous scar, blood, bone marrow,
      and lymph node aspirate) by parasitological (culture and smear exam) and
      molecular (DNA-based tests) methods. Specific anti-T. caninum and anti-Leishmania
      antibody production was also evaluated. Ten of 14 dogs infected by T. caninum
      showed a good general state at the time of diagnosis, and this status did not
      vary during the follow-up. Anti-T. caninum and anti-Leishmania IgG antibodies
      were detected by IFAT in 10 and 2 animals, respectively. Concomitant infection by
      Leishmania chagasi was confirmed in 2 dogs, indicating an overlap of endemic
      areas in Cuiaba. Trypanosoma caninum (parasite or DNA) was found only in the
      intact skin in all animals examined. Our results suggest that T. caninum
      infection can be manifested as an asymptomatic case with low humoral immune
      response.

PMID- 24328789
TI  - High-density lipoprotein cholesterol targeting for novel drug discovery: where
      have we gone wrong?
AB  - Lowering low-density lipoprotein-cholesterol (LDL-C) is an effective strategy to
      reduce cardiovascular risk. However, a significant residual risk remains in
      statin-treated patients. High-density lipoprotein cholesterol (HDL-C) is a
      strong, independent and inverse predictor of cardiovascular risk in many
      epidemiologic studies and has, therefore, emerged as a potential novel
      therapeutic target for addressing this substantial residual risk. Nevertheless,
      the failure of cholesteryl ester transfer protein (CETP) inhibitors and niacin in
      clinical trials has generated considerable speculation about the beneficial
      effects of HDL. Experimental studies have identified several HDL cardioprotective
      functions, including enhancement of macrophage reverse cholesterol transport and
      endothelial function and its antioxidant, anti-inflammatory and anti-thrombotic
      properties. Furthermore, HDL is highly heterogeneous and the atheroprotective
      functions of the different HDL subpopulations are not completely understood.
      Current available data indicate that increased HDL-C levels do not always
      correlate with enhanced HDL functions and, therefore, should not be considered a
      biomarker of HDL functionality. The clinical application of the novel HDL-based
      therapeutic approaches requires the development of validated and reproducible
      measures of key HDL functions. 

PMID- 24328791
TI  - Fe- but not Mg-protophorphyrin IX binds to a transmembrane b-type cytochrome.
AB  - Transmembrane b-type cytochromes, which are crucially involved in electron
      transfer chains, bind one or more heme (Fe-protoporphyrin IX) molecules non
      covalently. Similarly, chlorophylls are typically also non-covalently bound by
      several membrane integral polypeptides involved in photosynthesis. While both,
      chlorophyll and heme, are tetrapyrrole macrocycles, they have different
      substituents at the tetrapyrrole ring moiety. Furthermore, the central metal ion
      is Mg(2+) in chlorophyll and Fe(2+/3+) in heme. As heme and chlorophyll a have
      similar structures and might both be ligated by two histidine residues of a
      polypeptide chain, and as the local concentration of chlorophyll a might be up to
      100-times higher than the concentration of heme, the question arises, as to how
      an organism ensures specific binding of heme, but not of chlorophyll, to
      transmembrane apo-cytochromes involved in photosynthetic electron transfer
      reactions. As shown here, Fe-protoporphyrin IX derivatives with modified
      substituents at the tetrapyrrole ring moiety still bind to an apo-cytochrome;
      however, association appears to be reduced. This indicates that hydrophobic and
      polar interactions of the ring substituents with the protein moiety stabilize the
      protein/heme-complex but are not essential per se. However, removal or
      replacement of the central Fe-ion completely abolishes formation of a holo
      protein complex, and thus the central iron ion appears to determine heme binding
      to apo-cytochrome b6.

PMID- 24328790
TI  - Phosphorylation of Arabidopsis transketolase at Ser428 provides a potential
      paradigm for the metabolic control of chloroplast carbon metabolism.
AB  - Calcium is an important second messenger in eukaryotic cells that regulates many
      different cellular processes. To elucidate calcium regulation in chloroplasts, we
      identified the targets of calcium-dependent phosphorylation within the stromal
      proteome. A 73 kDa protein was identified as one of the most dominant proteins
      undergoing phosphorylation in a calcium-dependent manner in the stromal extracts
      of both Arabidopsis and Pisum. It was identified as TKL (transketolase), an
      essential enzyme of both the Calvin-Benson-Bassham cycle and the oxidative
      pentose phosphate pathway. Calcium-dependent phosphorylation of both Arabidopsis
      isoforms (AtTKL1 and AtTKL2) could be confirmed in vitro using recombinant
      proteins. The phosphorylation is catalysed by a stroma-localized protein kinase,
      which cannot utilize GTP. Phosphorylation of AtTKL1, the dominant isoform in most
      tissues, occurs at a serine residue that is conserved in TKLs of vascular plants.
      By contrast, an aspartate residue is present in this position in cyanobacteria,
      algae and mosses. Characterization of a phosphomimetic mutant (S428D) indicated
      that Ser428 phosphorylation exerts significant effects on the enzyme's substrate
      saturation kinetics at specific physiological pH values. The results of the
      present study point to a role for TKL phosphorylation in the regulation of carbon
      allocation.

PMID- 24328792
TI  - Photocontrolled adsorption of polyelectrolyte molecules on a silicon substrate.
AB  - We report on a change in the properties of monomolecular films of polyelectrolyte
      molecules, induced by illuminating the silicon substrate on which they adsorb. It
      was found that under illumination the thickness of the adsorbed layer decreases
      by at least 27% and at the same time the roughness is significantly reduced in
      comparison to a layer adsorbed without irradiation. Furthermore, the homogeneity
      of the film topography and the surface potential is shown to be improved by
      illumination. The effect is explained by a change in surface charge density under
      irradiation of n- and p-type silicon wafers. The altered charge density in turn
      induces conformational changes of the adsorbing polyelectrolyte molecules. Their
      photocontrolled adsorption opens new possibilities for selective manipulation of
      adsorbed films. This possibility is of potential importance for many applications
      such as the production of well-defined coatings in biosensors or
      microelectronics. 

PMID- 24328793
TI  - Development of a novel preclinical model of pneumococcal pneumonia in nonhuman
      primates.
AB  - Pneumococcal pneumonia is a leading cause of bacterial infection and death
      worldwide. Current diagnostic tests for detecting Streptococcus pneumoniae can be
      unreliable and can mislead clinical decision-making and treatment. To address
      this concern, we developed a preclinical model of pneumococcal pneumonia in
      nonhuman primates useful for identifying novel biomarkers, diagnostic tests, and
      therapies for human S. pneumoniae infection. Adult colony-bred baboons (n = 15)
      were infected with escalating doses of S. pneumoniae (Serotype 19A-7). We
      characterized the pathophysiological and serological profiles of healthy and
      infected animals over 7 days. Pneumonia was prospectively defined by the presence
      of three criteria: (1) change in white blood cell count, (2) isolation of S.
      pneumoniae from bronchoalveolar lavage fluid (BALF) or blood, and (3) concurrent
      signs/symptoms of infection. Animals given 10(9) CFU consistently met our
      definition and developed a phenotype of tachypnea, tachycardia, fever, hypoxemia,
      and radiographic lobar infiltrates at 48 hours. BALF and plasma cytokines,
      including granulocyte colony-stimulating factor, IL-6, IL-10, and IL-1ra, peaked
      at 24 to 48 hours. At necropsy, there was lobar consolidation with frequent
      pleural involvement. Lung histopathology showed alveolar edema and macrophage
      influx in areas of organizing pneumonia. Hierarchical clustering of peripheral
      blood RNA data at 48 hours correctly identified animals with and without
      pneumonia. Dose-dependent inoculation of baboons with S. pneumoniae produces a
      host response ranging from spontaneous clearance (10(6) CFU) to severe pneumonia
      (10(9) CFU). Selected BALF and plasma cytokine levels and RNA profiles were
      associated with severe pneumonia and may provide clinically useful parameters
      after validation.

PMID- 24328795
TI  - Insight into protein S-nitrosylation in Chlamydomonas reinhardtii.
AB  - AIMS: Protein S-nitrosylation, a post-translational modification (PTM) consisting
      of the covalent binding of nitric oxide (NO) to a cysteine thiol moiety, plays a
      major role in cell signaling and is recognized to be involved in numerous
      physiological processes and diseases in mammals. The importance of nitrosylation
      in photosynthetic eukaryotes has been less studied. The aim of this study was to
      expand our knowledge on protein nitrosylation by performing a large-scale
      proteomic analysis of proteins undergoing nitrosylation in vivo in Chlamydomonas
      reinhardtii cells under nitrosative stress. RESULTS: Using two complementary
      proteomic approaches, 492 nitrosylated proteins were identified. They participate
      in a wide range of biological processes and pathways, including photosynthesis,
      carbohydrate metabolism, amino acid metabolism, translation, protein folding or
      degradation, cell motility, and stress. Several proteins were confirmed in vitro
      by western blot, site-directed mutagenesis and activity measurements. Moreover,
      392 sites of nitrosylation were also identified. These results strongly suggest
      that S-nitrosylation could constitute a major mechanism of regulation in C.
      reinhardtii under nitrosative stress conditions. INNOVATION: This study
      constitutes the largest proteomic analysis of protein nitrosylation reported to
      date. CONCLUSION: The identification of 381 previously unrecognized targets of
      nitrosylation further extends our knowledge on the importance of this PTM in
      photosynthetic eukaryotes. The data have been deposited to the ProteomeXchange
      repository with identifier PXD000569.

PMID- 24328796
TI  - Psychosocial and psychological factors associated with post-traumatic stress
      disorder following traumatic brain injury in adult civilian populations: a
      systematic review.
AB  - PRIMARY OBJECTIVE: Increasing support exists for the development of post
      traumatic stress disorder (PTSD) after traumatic brain injury (TBI). Despite the
      psychological nature of PTSD, previous reviews have mainly focused on the injury
      related and neurological characteristics of its presentation in TBI.
      Consequently, this review systematically examined the psychological and
      psychosocial variables associated with PTSD symptoms after TBI in civilian
      adults. METHODS: Detailed searching retrieved 28 relevant articles which met the
      inclusion criteria. Each article underwent a thorough quality assessment
      procedure and data were extracted relevant to the review's aims. RESULTS: Results
      highlighted several psychological and psychosocial variables associated with PTSD
      after TBI, including historical factors and those which become relevant after the
      traumatic event. Furthermore, the results indicated that some factors were not
      associated with PTSD after TBI, despite a relationship existing with PTSD in the
      general population. The findings of the quality assessment were utilized
      throughout the formation of results. CONCLUSIONS: The review highlights the
      importance of addressing psychological and psychosocial factors within the
      assessment and treatment of PTSD after TBI. The limitations of the research are
      highlighted and the clinical and research implications discussed.

PMID- 24328797
TI  - Does acute TBI-related sleep disturbance predict subsequent neuropsychiatric
      disturbances?
AB  - PRIMARY OBJECTIVE: To determine whether sleep disturbance in the acute post
      traumatic brain injury (TBI) period predicts symptoms of depression, anxiety or
      apathy measured 6 and 12 months after TBI. RESEARCH DESIGN: Longitudinal,
      observational study. METHODS AND PROCEDURES: First time closed-head injury
      patients (n = 101) were recruited and evaluated within 3 months of injury and
      followed longitudinally, with psychiatric evaluations at 6 and 12 months post
      injury. Pre- and post-injury sleep disturbances were measured via the Medical
      Outcome Scale (MOS) for Sleep. Subjects were also assessed for anxiety,
      depression, apathy, medical comorbidity and severity of TBI. MAIN OUTCOMES AND
      RESULTS: Sleep disturbance in the acute TBI period was associated with increased
      symptoms of depression, anxiety and apathy 12 months post-injury. CONCLUSIONS:
      Sleep disturbances experienced soon after trauma (i.e. <3 months after injury)
      predicted neuropsychiatric symptoms 1 year after injury, raising two important
      clinical questions: (1) Is sleep disturbance soon after trauma a prognostic
      marker of subsequent neuropsychiatric symptoms? and (2) Can early treatment of
      sleep disturbance during the post-TBI period reduce subsequent development of
      neuropsychiatric symptoms? Future studies with larger sample sizes and
      appropriate control groups could help to answer these questions, using evidence
      based methods for evaluating and treating sleep disturbances.

PMID- 24328798
TI  - Early neuropsychological tests as correlates of return to driving after traumatic
      brain injury.
AB  - OBJECTIVE: To assess the ability of neuropsychometric tests administered during
      inpatient rehabilitation to predict return to driving after traumatic brain
      injury (TBI). DESIGN: Retrospective, matched case-controlled study. METHODS:
      Sixty-seven participants with TBI, drawn from an existing database, completed a
      questionnaire that assessed return to driving post-TBI, as measured by
      reinstatement of the driver's license. Drivers were individually case-matched to
      non-drivers on age, Glasgow Coma Scale (GCS), Disability Rating Scale (DRS) and
      the rehabilitation admission interval (RAI). Scores on four neuropsychological
      tests (Trail-Making A, Trail Making B, Digit Span-forward and Digit Span
      backward), administered during the rehabilitation stay, were compared between
      case-matched drivers and non-drivers. OUTCOME MEASURE: Return to driving, as
      defined by reinstatement of the driver's license. RESULTS: Participants who had
      returned to driving were comparable to those who had not returned to driving with
      respect to demographic variables, initial injury severity and baseline
      functioning. Scores on two neuropsychological assessments were significantly
      better in participants who had returned to driving than in those who had not:
      Trail-making A (p < 0.01) and Trail-making B (p < 0.01). CONCLUSIONS: The results
      suggest that neuropsychological measures of processing speed and cognitive
      flexibility may predict return to driving after TBI.

PMID- 24328799
TI  - Efficacy of a post-acute interval inpatient neurorehabilitation programme for
      severe brain injury.
AB  - BACKGROUND: Patients with severe acute brain injury often suffer from prolonged
      limitations in the activities of daily living (ADL) after completion of initial
      neurorehabilitation. OBJECTIVE: To analyse the efficacy of an inpatient interval
      rehabilitation programme (IRP) focused on patient goals in the chronic disease
      state. METHODS: Retrospective longitudinal cohort study of IRP patients. Clinical
      scoring of ADLs was performed weekly during inpatient treatment. IRP success was
      rated with the Goal Attainment Scale. Regression analysis was used to identify
      factors that influence IRP success. RESULTS: Data from 125 patients (50.4 years)
      were analysed. Delay between discharge from acute/sub-acute rehabilitation and
      admission to IRP was 552 days. IRP lasted for 46 days and 37% of rehabilitation
      attempts were rated as successful. A significant increase in FIM scores from 33
      +/- 22 to 36 +/- 24 points (p < 0.001) occurred. Higher ADL scores at discharge
      from acute/sub-acute rehabilitation and decannulation of a tracheostomy tube as
      the primary IRP goal made an IRP success more likely. CONCLUSIONS: Even several
      years after severe acute brain injury, an ICF-oriented IRP can lead to ADL
      improvements and achievement of specific goals. If confirmed by prospective
      trials, this strategy should be incorporated in healthcare systems.

PMID- 24328800
TI  - Physiological emotional under-arousal in individuals with mild head injury.
AB  - PRIMARY OBJECTIVES: This study examined the potential emotional sequelae
      following self-reported mild head injury (MHI; e.g. 'altered state of
      consciousness' [ASC]) in university students with a particular focus on arousal
      status and responsivity to experimental manipulation of arousal. RESEARCH DESIGN:
      A quasi-experimental design (n = 91) was used to examine arousal status (self
      reported and physiological indices) and response to manipulated arousal (i.e.
      induced psychosocial stress/activation; reduced activation/relaxation) between
      persons who acknowledged prior MHI and persons with no-MHI. MAIN OUTCOME AND
      RESULTS: University students who self-reported MHI were physiologically under
      aroused and less responsive to stressors (both laboratory and environmental)
      compared to their no-MHI cohort. Those with reported loss of consciousness
      demonstrated the most attenuated emotional arousal responses (i.e. flattened
      electrodermal responsivity) relative to those with only a reported ASC, followed
      by those with no-MHI. CONCLUSIONS: The under-arousal in traumatic brain injury
      has been hypothesized to be associated with ventromedial prefrontal cortex
      disruption. This under-arousal may be mirrored in persons who self-report
      experiencing subtle head trauma. Students who reported MHI may be less able to
      physiologically respond and/or cognitively appraise stressful experiences as
      compared to their no-MHI cohort; and experience subtle persistent consequences
      despite the subtle nature of the reported head trauma.

PMID- 24328801
TI  - Interpretation of magnetic resonance imaging in the chronic phase of traumatic
      brain injury: what is missed in the original reports?
AB  - PRIMARY OBJECTIVE: To find eventual differences in detecting the late stage TBI
      findings in MRI between two neuroradiologists and to compare the results with the
      original reports. METHODS AND PROCEDURE: Two neuroradiologists with different
      levels of experience (R1 and R2) reviewed 89 cranial 1.5 T MRI examinations of
      patients with clinically evident TBI. They recorded the nature, location and side
      of the finding and stated their view of traumatic axonal injury (TAI). The
      original reports were reviewed accordingly. MAIN OUTCOMES AND RESULTS: TAI was
      reported as being evident or possible in 51 patients with TBI. However, only 30
      (76%) of these concerned the same patients. R1 reported more contusion findings,
      but both found the same number of spot-like haemorrhages. The most striking
      difference was in the reporting of localized atrophy. R1 reported atrophy in
      51/178 (29%) frontal lobes, whereas R2 in 14/178 (8%). Many of the findings were
      missed in the original reports. CONCLUSIONS: The interpretation of TBI findings
      in late stage MRI yields significant variability between neuroradiologists. This
      may endanger diagnostics and lead to false treatment decisions and medico-legal
      problems. Standardized quantitative imaging analysis programs and advances in MRI
      technology should be utilized to improve radiological TBI diagnosis.

PMID- 24328802
TI  - Adjusting to persistent post-concussive symptoms following mild traumatic brain
      injury and subsequent psycho-educational intervention: a qualitative analysis in
      military personnel.
AB  - OBJECTIVE: Best practice guidelines outline ways in which mild traumatic brain
      injury (mTBI) and persistent post-concussive symptoms (PPCS) should be managed.
      In line with the existing evidence base, DMRC Headley Court established a
      treatment programme for UK servicemen and women with mTBI. This study explored
      the experiences of a sample of UK military personnel living with PPCS, who also
      received psycho-educational intervention (Phase 2) at this unit. SETTING: DMRC
      Headley Court, Southeast England. PARTICIPANTS: Sixteen service personnel who had
      completed the intervention within 24 months prior to interview. DESIGN: Semi
      structured qualitative interview study, with purposive sampling and thematic
      analysis. RESULTS: Participants described their mTBI in terms of: (1) onset; (2)
      subsequent symptom experience; (3) recovery; and (4) acceptance. All participants
      reported a significant degree of confusion and chaos in the aftermath of their
      traumatic event. These themes highlighted how, following enrolment onto the Phase
      2 intervention at DMRC Headley Court, participants reported being (largely) able
      to manage PPCS. Further, many reported acceptance of their condition and
      described how they had managed to re-establish a sense of order. CONCLUSIONS:
      Following a flexible and tailored intervention for PPCS, patients report feeling
      empowered and describe having a renewed sense of stability.

PMID- 24328803
TI  - Acquired brain injury services in the Republic of Ireland: experiences and
      perceptions of families and professionals.
AB  - PRIMARY OBJECTIVE: This study aimed to highlight the experiences and perceptions
      of rehabilitation services among families of people with Acquired Brain Injury
      (ABI) and among professionals working in ABI rehabilitation services in Ireland.
      RESEARCH DESIGN: A qualitative, exploratory study used focus groups to gather
      data. Data were analysed through a system of qualitative content analysis.
      METHOD: Three focus groups were carried out involving families of people with ABI
      from different parts of Ireland and one focus group was carried out with
      professionals working in rehabilitation services. Participants in all groups
      responded to five broad semi-structured questions. MAIN RESULTS: Analysis
      revealed five categories across the family focus groups and, separately, five
      categories within the professional group. Both groups highlighted that: there is
      a need to develop rehabilitation services in Ireland, building and expanding on
      current services; there is a need to make information and education related to
      brain injury more widely available and to ensure it is accessible for families;
      and there is a need to improve co-ordination and communication between services.
      A range of relationship issues were also highlighted. CONCLUSIONS: Much remains
      to be done to improve the experiences and perceptions of brain injury
      rehabilitation services among families and professionals.

PMID- 24328804
TI  - How the burden of caring for a patient in a vegetative state changes in relation
      to different coping strategies.
AB  - OBJECTIVE: To differentiate the burden of caregivers of patients in a vegetative
      state (VS) on the basis of different coping strategies and prolonged grief.
      METHODS: An observational multi-centre study was conducted with 61 caregivers of
      VS patients hospitalized in specialized units in Italy. The Anxiety and
      Depression Short Scale, the Prolonged Grief 12 and Family Strain Questionnaire
      were used to measure caregivers' burden and the Coping Orientations to Problem
      Experiences to identify the coping strategies used by caregivers. A hierarchical
      cluster analysis was carried out to group the data and a comparison between
      clusters was conducted. RESULTS: Caregivers were grouped in two clusters defined
      by the major proximity among the cases of the same group and the major distance
      from the cases of the other group. The first group was characterized by lower
      levels of anxiety, depression, family strain and prolonged grief. This group
      mainly used coping strategies referring to three factors: Social Support,
      Positive Attitude and Problem Oriented. The second group showed higher levels of
      anxiety, depression, family strain and prolonged grief and used the Avoidance
      strategies more than the first group. CONCLUSIONS: The burden of providing care
      to a VS patient is mediated by a range of factors including the different coping
      strategies adopted by caregivers. Support for these caregivers should take this
      consideration into account and should be subsequently personalized.

PMID- 24328805
TI  - Facial affect recognition difficulties in traumatic brain injury rehabilitation
      services.
AB  - PRIMARY OBJECTIVE: The occurrence of facial affect recognition difficulties in a
      sample of people accessing traumatic brain injury (TBI) rehabilitation services
      was examined. It was hypothesized that between 13-39% of participants would
      demonstrate clinically significant impairment in facial affect recognition.
      RESEARCH DESIGN: Cross-sectional sample of eligible participants who were current
      clients of eight brain injury services were invited to participate. METHODS AND
      PROCEDURES: Forty-five participants with mild-to-severe TBI were assessed for
      facial affect recognition difficulties using the facial affect discrimination,
      naming, selection and matching sub-tests of the Florida Affect Battery. MAIN
      OUTCOMES AND RESULTS: Fifty-one per cent of participants had at least moderate
      difficulties with facial affect recognition. CONCLUSIONS: The current sample was
      not a random selection from the population of people with TBI, so the results do
      not establish a formal estimate of prevalence. Nonetheless, the data indicate
      that when assessing typical clients with severe brain injuries presenting to
      neurorehabilitation services, there is likely to be a high frequency of
      occurrence of facial affect recognition difficulties. Rehabilitation outcomes may
      be improved by screening for and treating facial affect recognition difficulties
      following TBI. Further examination and development of treatment options is
      warranted.

PMID- 24328806
TI  - Quality-of-life after brain injury in childhood: time, not severity, is the
      significant factor.
AB  - OBJECTIVE: Little is known about the impact of acquired brain injury (ABI) on the
      long-term quality-of-life (QoL) in children and youth. The objectives of this
      study were to illustrate the long-term QoL trajectories at 5 years post-ABI.
      METHODS: The QoL of children between 5-18 years (n = 94) admitted to McMaster
      Children's Hospital with ABI were assessed longitudinally for a minimum of 5
      years post-injury using the Child Health Questionnaire. Independent t-tests were
      used to examine differences in QoL between the study cohort and a normative
      sample at different time points. Mixed-effects models were used to identify
      predictors for QoL. RESULTS: The QoL of children with ABI was significantly
      poorer (p < 0.05) than the normative data on all domains and at all-time points
      except at baseline. The CHQ physical summary score (PHSS) showed a significant
      decline immediately after injury and a significant recovery at 8 months post
      injury; while the CHQ psychosocial summary score (PSSS) showed a significant
      immediate decline, which remained over the course of the study. Pre-morbid school
      record, time post-injury and mechanism of injury significantly predicted the CHQ
      PSSS. CONCLUSIONS: QoL is impacted by ABI regardless of severity. This impact is
      further affected by time post-injury.

PMID- 24328807
TI  - Highly regioselective three-component domino Heck-Negishi coupling reaction for
      the functionalization of purines at C6.
AB  - A highly regioselective three-component domino Heck-Negishi coupling reaction has
      been developed. Organozinc reagents are used to trap an alkylpalladium
      intermediate of olefins for a first example in the domino Heck reaction. This
      reaction is applicable to acrylates (or acrylamides) and purine compounds,
      producing a series of novel purine compounds with carbon substituents at the C6
      position in moderate to good yields. 

PMID- 24328809
TI  - Trends and issues in oncology costs.
AB  - Approximately 18% of US gross domestic product is spent on healthcare and 5% of
      that is for cancer care. With rapidly increasing oncologic drug prices, growth in
      cancer spending will likely far outpace overall healthcare spending growth.
      Developing cost-saving strategies is imperative, but economizing must not
      compromise patients' well-being. Providing quality care at the most economical
      price is the main aim. This article summarizes trends in rising cancer costs, and
      reviews cost-management strategies, including those proposed in the Affordable
      Care Act. Many programs economize by correcting inefficiencies, preventing
      therapeutic failures and eliminating errors. Process improvement is important,
      but in oncology, medications substantially drive costs. Identifying the most
      effective and economical treatments requires cost-effectiveness research. At the
      current pace, the US payers cannot continue to afford increasing costs for cancer
      treatments. Research on maximizing patient outcomes for reasonable costs is
      essential. More analyses of quality of life assessment and cost-effectiveness can
      support future decisions about cancer care. 

PMID- 24328808
TI  - Neurobiological mechanisms underlying relapse to cocaine use: contributions of
      CRF and noradrenergic systems and regulation by glucocorticoids.
AB  - Considering its pervasive and uncontrollable influence in drug addicts,
      understanding the neurobiological processes through which stress contributes to
      drug use is a critical goal for addiction researchers and will likely be
      important for the development of effective medications aimed at relapse
      prevention. In this paper, we review work from our laboratory and others focused
      on determining the neurobiological mechanisms that underlie and contribute to
      stress-induced relapse of cocaine use with an emphasis on the actions of
      corticotropin-releasing factor in the ventral tegmental area (VTA) and a key
      pathway from the bed nucleus of the stria terminalis to the VTA that is regulated
      by norepinephrine and beta adrenergic receptors. Additionally, we discuss work
      suggesting that the influence of stress in cocaine addiction changes and
      intensifies with repeated cocaine use in an intake-dependent manner and examine
      the potential role of glucocorticoid hormones in the underlying drug-induced
      neuroadaptations. It is our hope that research in this area will inform clinical
      practice and medication development aimed at minimizing the contribution of
      stress to the addiction cycle, thereby improving treatment outcomes and reducing
      the societal costs of addiction.

PMID- 24328810
TI  - Directed assembly of lamellae forming block copolymer thin films near the order
      disorder transition.
AB  - The impact of thin film confinement on the ordering of lamellae was investigated
      using symmetric poly(styrene-b-[isoprene-ran-epoxyisoprene]) diblock copolymers
      bound by nonpreferential wetting interfaces. The order-disorder transition
      temperature (TODT) and the occurrence of composition fluctuations in the
      disordered state are not significantly affected by two-dimensional confinement.
      Directed self-assembly using chemical patterning is demonstrated near TODT. These
      results establish the minimum feature size attainable using directed self
      assembly of a given diblock copolymer system. 

PMID- 24328811
TI  - Bidirectional syntactic priming across cognitive domains: from arithmetic to
      language and back.
AB  - Scheepers et al. [Scheepers, C., Sturt, P., Martin, C. J., Myachykov, A., Teevan,
      K., & Viskupova, I. (2011). Structural priming across cognitive domains: From
      simple arithmetic to relative clause attachment. Psychological Science, 22, 1319
      1326. doi:10.1177/0956797611416997] showed that the structure of a correctly
      solved mathematical equation affects how people subsequently complete sentences
      containing high versus low relative-clause attachment ambiguities. Here we
      investigated whether such effects generalize to different structures and tasks
      and, importantly, whether they also hold in the reverse direction (i.e., from
      linguistic to mathematical processing). In a questionnaire-based experiment,
      participants had to solve structurally left- or right-branching equations (e.g.,
      5 * 2 + 7 versus 5 + 2 * 7) and to provide sensicality ratings for structurally
      left- or right-branching adjective-noun-noun compounds (e.g., alien monster movie
      versus lengthy monster movie). In the first version of the experiment, the
      equations were used as primes and the linguistic expressions as targets
      (investigating structural priming from maths to language). In the second version,
      the order was reversed (language-to-maths priming). Both versions of the
      experiment showed clear structural priming effects, conceptually replicating and
      extending the findings from Scheepers and colleagues (2011). Most crucially, the
      observed bidirectionality of cross-domain structural priming strongly supports
      the notion of shared syntactic representations (or recursive procedures to
      generate and parse them) between arithmetic and language. 

PMID- 24328812
TI  - The tail wags the dog: possible mechanism for reverse allosteric control of
      ligand-activated channels.
AB  - In this issue of the British Journal of Pharmacology, a new article by Kozuska et
      al. discusses the multiple salt bridges in the intracellular domain of the 5HT3A
      receptor. These interactions increase the overall rigidity of the receptor,
      stabilize its low conducting state and affect the ligand cooperativity. The
      authors suggest that the allosteric effects of these regions on the receptor may
      be involved in a possible 'reverse' allosteric modulation of 5HT3 receptors.

PMID- 24328813
TI  - Lead exposure affects inflammatory mediators, total and differential white blood
      cells in sensitized guinea pigs during and after sensitization.
AB  - BACKGROUND: Serum inflammatory mediators and white blood cells (WBC) counts in
      the blood of sensitized and lead exposed guinea pigs were evaluated. METHODS:
      Guinea pigs were randomly allocated into control (C), sensitized (S) and
      sensitized groups exposed to three lead concentrations (0.1, 0.2 and 0.4 M)
      during (DS) and after sensitization (PS), (n = 6 for each group). Animals were
      sensitized by intra-peritoneal injection and aerosol inhalation of ovalbumin
      (OA). Serum total protein, PLA2, IgE, histamine, total and differential WBC
      counts of blood were evaluated. RESULTS: Serum PLA2, total protein, IgE,
      histamine, total and differential WBC counts in all three sensitized groups were
      significantly increased, but the percentage of lymphocyte was decreased compared
      to control group (p < 0.05 to p < 0.001). Serum total protein and total WBC
      number in all animals exposed to lead as well as the eosinophil and histamine in
      animals exposed to highest lead concentration and IgE in sensitized groups
      exposed to lead after sensitization were significantly higher, but the lymphocyte
      in animals exposed to two higher lead concentrations was lower than non exposed
      sensitized group (p < 0.05 to p < 0.001). The changes in all parameters in lead
      exposed animals after sensitization were higher than those during sensitization
      which was statistically significant for total WBC count in the animals exposed to
      low lead concentration (p < 0.05). CONCLUSION: Inhaled lead can increase serum
      total protein, PLA2, IgE and histamine levels, total and most differential WBC
      counts in sensitized animal which was more pronounced in animals exposed to lead
      after compared to those during sensitization.

PMID- 24328814
TI  - The biological clock modulates the human cortisol response in a multiplicative
      fashion.
AB  - Human cortisol levels follow a clear circadian rhythm. We investigated the
      contribution of alternation of sleep and wakefulness and the circadian clock,
      using forced desynchrony. Cortisol levels were best described by a multiplication
      of a circadian and a wake-time component. The human cortisol response is
      modulated by circadian phase. Exposure to stress at an unnatural phase, as in
      shift work, is predicted to result in abnormal cortisol levels. Health of shift
      workers may therefore improve when stress is reduced at times when the clock
      produces high stress sensitivity. 

PMID- 24328815
TI  - Is there a diurnal variation in repeated sprint ability on a non-motorised
      treadmill?
AB  - In active males, muscle force production and short-term (<6 s) anaerobic
      performance are significantly greater in the evening compared with the morning.
      This diurnal variation is attributed to motivational, peripheral and central
      factors, and possibly the higher core and muscle temperatures observed in the
      evening. However, little is known regarding whether diurnal variation on a
      treadmill also exists in team-sport specific tests of repeated sprint ability
      (RSA), as would be relevant to football, for example. A controlled laboratory
      protocol using a non-motorised treadmill has been used to investigate whether
      daily variation in RSA is present in highly motivated athletes. Twenty active
      males (mean +/- SD: age, 21.0 +/- 2.2 yrs; maximal oxygen uptake ([Formula: see
      text] max), 60.8 +/- 4.8 ml kg min(-1); body mass, 77.02 +/- 10.5 kg and height,
      1.79 +/- 0.07 m) volunteered and completed two sessions counterbalanced in order
      of administration (separated by >48 h): a morning (M, 07:30 h) and evening (E,
      17:30 h) session. Both sessions included a 5-min active warm-up on a motorised
      treadmill at 10 km h(-1) followed by three task-specific warm-up sprints at 50%,
      70% and 80%, respectively, on a non-motorised treadmill. During each trial, 10 *
      3 s repeated sprints with 30 s recoveries were performed on the non-motorised
      treadmill. Rectal (Trec) and muscle temperature measurements (Tm) were taken
      after subjects had reclined for 30 min at the start of the protocol, and again
      after the active warm-up. Values of heart rate, thermal comfort (TC), rating of
      perceived exertion (RPE) and effort were measured throughout. Blood samples were
      taken at rest, after the sprints and 5-min post sprints. Data were analysed using
      a GLM with repeated measures. Trec and Tm values were higher at rest in the
      evening than the morning (0.46  degrees C and 0.57  degrees C, respectively, p <
      0.05). Distance covered, peak power, average power, peak velocity and average
      velocity all showed significantly higher values in the evening compared with the
      morning (a range of 3.3-8.3%, p < 0.05), with peak power displaying a statistical
      trend (0.10 > p > 0.05). All subjects reported maximal values for "effort" for
      each sprint. There were significant positive correlations between Trec and Tm,
      Trec and RPE, TC and all measures of RSA performance. However, there was no
      correlation between fatigue index for peak power output or peak velocity and
      Trec. In summary, in this population of motivated subjects, time-of-day effects
      were seen in resting Trec and Tm values and all performance measures of RSA, in
      partial agreement with past research. The diurnal variation in Trec and Tm cannot
      fully explain time-of-day oscillations in RSA on a non-motorised treadmill.
      Although central temperature may provide some endogenous rhythm to human
      performance, the causal link seems to be due to a multiplicity of components and
      mechanisms.

PMID- 24328816
TI  - Rhythmic egg-laying behaviour in virgin females of fruit flies Drosophila
      melanogaster.
AB  - Fruit fly Drosophila melanogaster females display rhythmic egg-laying under 12:12
      h light/dark (LD) cycles which persists with near 24 h periodicity under constant
      darkness (DD). We have shown previously that persistence of this rhythm does not
      require the neurons expressing pigment dispersing factor (PDF), thought to be the
      canonical circadian pacemakers, and proposed that it could be controlled by
      peripheral clocks or regulated/triggered by the act of mating. We assayed egg
      laying behaviour of wild-type Canton S (CS) females under LD, DD and constant
      light (LL) conditions in three different physiological states; as virgins, as
      females allowed to mate with males for 1 day and as females allowed to mate for
      the entire duration of the assay. Here, we report the presence of a circadian
      rhythm in egg-laying in virgin D. melanogaster females. We also found that egg
      laying behaviour of 70 and 90% females from all the three male presence/absence
      protocols follows circadian rhythmicity under DD and LL, with periods ranging
      between 18 and 30 h. The egg-laying rhythm of all virgin females synchronized to
      LD cycles with a peak occurring soon after lights-off. The rhythm in virgins was
      remarkably robust with maximum number of eggs deposited immediately after lights
      off in contrast to mated females which show higher egg-laying during the day.
      These results suggest that the egg-laying rhythm of D. melanogaster is
      endogenously driven and is neither regulated nor triggered by the act of mating;
      instead, the presence of males results in reduction in entrainment to LD cycles.

PMID- 24328817
TI  - Psychological factors predicting the distress to female persistent genital
      arousal symptoms.
AB  - Symptoms of persistent genital arousal are expected to negatively affect women's
      sexual and emotional well-being. However, not all women who experience persistent
      genital arousal complain about their genital condition. Against this background,
      this study aimed to evaluate psychological predictors of the distress associated
      with persistent genital arousal symptoms, as well as psychological moderators
      influencing the conditions under which persistent genital arousal causes
      distress. A total of 117 women reporting symptoms of persistent genital arousal
      answered to online questionnaires measuring personality traits, sexual beliefs,
      and dyadic adjustment. Women have also completed a checklist measuring the
      frequency/severity of persistent genital arousal symptoms and the
      distress/impairment caused by these symptoms. Results showed that neuroticism,
      (low) openness, sexual conservatism, and (low) dyadic adjustment significantly
      predicted distress associated with genital symptoms. Furthermore, sexual
      conservatism was found to moderate the relation between the symptoms' severity
      and the distress associated with those symptoms. Overall, sexual conservatism
      seems to be a key differentiator factor, influencing the psychological conditions
      under which women may report higher levels of distress caused by persistent
      genital arousal. Because such findings focus on the distress to genital arousal
      symptoms rather than on persistent genital arousal disorder as a clinical entity,
      the results under consideration may or may not characterize women formally
      assigned to the persistent genital arousal disorder label. 

PMID- 24328818
TI  - The Bidimensional Impression Management Index (BIMI): measuring agentic and
      communal forms of impression management.
AB  - Measures of impression management have yet to incorporate two-factor models of
      person perception. The 2 primary factors are often labeled agency and communion.
      In Study 1, we assembled a new measure of impression management-the Bidimensional
      Impression Management Index (BIMI): It comprises 2 subscales designed
      specifically to tap agentic and communal content. Both subscales showed adequate
      alpha reliabilities under both honest and faking conditions. In Study 2, the BIMI
      was cross-validated in a new sample: The subscales remained relatively
      independent, and their reliabilities remained solid. A coherent pattern of
      personality correlates also supported the validities of both subscales. In Study
      3, the differential sensitivity of the 2 subscales was demonstrated by
      manipulating the job type in simulated job applications. Implications and
      applications of the BIMI are discussed.

PMID- 24328820
TI  - The complete mitochondrial genome sequence of Eimeria magna (Apicomplexa:
      Coccidia).
AB  - In the present study, we determined the complete mitochondrial DNA (mtDNA)
      sequence of Eimeria magna from rabbits for the first time, and compared its gene
      contents and genome organizations with that of seven Eimeria spp. from domestic
      chickens. The size of the complete mt genome sequence of E. magna is 6249 bp,
      which consists of 3 protein-coding genes (cytb, cox1 and cox3), 12 gene fragments
      for the large subunit (LSU) rRNA, and 7 gene fragments for the small subunit
      (SSU) rRNA, without transfer RNA genes, in accordance with that of Eimeria spp.
      from chickens. The putative direction of translation for three genes (cytb, cox1
      and cox3) was the same as those of Eimeria species from domestic chickens. The
      content of A + T is 65.16% for E. magna mt genome (29.73% A, 35.43% T, 17.09 G
      and 17.75% C). The E. magna mt genome sequence provides novel mtDNA markers for
      studying the molecular epidemiology and population genetics of Eimeria spp. and
      has implications for the molecular diagnosis and control of rabbit coccidiosis.

PMID- 24328821
TI  - The complete mitochondrial genome sequence of Tor sinensis (Cypriniformes,
      Cyprinidae).
AB  - The complete mitogenome sequence of Tor sinensis was determined using long PCR
      reactions. The genome is 16,579 bp in length, including 13 typical vertebrate
      protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and a control
      region. Except for eight tRNA and ND6 genes, all other mitochondrial genes are
      encoded on the heavy strand. The gene order and composition of T. sinensis was
      similar to that of most other vertebrates. The descending order of the base
      composition on heavy strand was 31.9% A, 27.4% C, 24.9% T, 15.7% G, with a
      relatively lower level of G and a slight AT bias of 56.8%. The codon usage
      followed the typical vertebrate mitochondrial pattern (ATG or GTG for start codon
      and TAA or TAG for stop codon). There are 9 regions of gene overlap totaling 29
      bp and 14 inter-genic spacer regions totaling 71 bp.

PMID- 24328822
TI  - The complete mitogenome sequence of Ptychobarbus dipogon (Cypriniformes:
      Cyprinidae).
AB  - The complete mitochondrial genome of Ptychobarbus dipogon is 16,787 bp in length,
      consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA
      genes and 2 non-coding regions: control region (CR) and origin of light-strand
      replication (OL). The gene order of P. dipogon mitogenome is similar to those
      observed in most other vertebrates. The complete mitogenome sequence of P.
      dipogon can provide useful data for further studies on population structure,
      phylogenetics and conservation genetics of this species. 

PMID- 24328823
TI  - Genetic differences between Chabertia ovina and C. erschowi revealed by sequence
      analysis of four mitochondrial genes.
AB  - This study examined sequence differences in mitochondrial cytochrome c oxidase
      subunit 1 (cox1), large subunit ribosomal RNA (rrnL) and NADH dehydrogenase
      subunits 1 and 4 (nad1 and nad4) between Chabertia ovina and C. erschowi from
      yaks in Qinghai and goats in Shaanxi provinces, China. A part of the cox1
      (pcox1), rrnL (prrnL), nad1 and nad4 genes (pnad1 and pnad4) were amplified
      separately from individual nematodes by PCR and sequenced. The length of the
      sequences of pcox1, prrnL, pnad1 and pnad4 was 441 bp, 450 bp, 526 bp and 914 bp
      for C. ovina, and 441 bp, 451 bp, 517 bp and 810 bp for C. erschowi,
      respectively. The intra-specific sequence variations within C. ovina were 0.2
      2.9% for pcox1, 0-0.9% for prrnL, 0.6-2.3% for pnad1, and 0.4-2.0% for pnad4, and
      were 0.5-1.6% for pcox1, 0-1.1% for prrnL, 0.2-1.7% for pnad1, and 0.4-1.1% for
      pnad4 within C. erschowi. Whereas, the inter-specific sequence differences
      between the two species were obviously higher, being 11.6-12.9% for pcox1, 9.8
      11.1% for prrnL, 14.4-15.9% for pnad1, and 16.4-17.7% for pnad4. Phylogenetic
      analyses using Bayesian inference (BI), based on combined sequences of four
      genes, indicated that the C. ovina and C. erschowi represent distinct species.
      These results demonstrate that these mt gene sequences provide novel genetic
      markers for the identificaiton and differentiation C. ovina and C. erschowi, and
      have implications for studying the population genetics and molecular epidemiology
      of Chabertia spp.

PMID- 24328819
TI  - Exploiting oxidative microenvironments in the body as triggers for drug delivery
      systems.
AB  - SIGNIFICANCE: Reactive oxygen species and reactive nitrogen species (ROS/RNS)
      play an important role in cell signaling pathways. However, the increased
      production of these species may disrupt cellular homeostasis, giving rise to
      pathological conditions. Biomaterials that are responsive to ROS/RNS can be
      strategically used to specifically release therapeutics and diagnostic agents to
      regions undergoing oxidative stress. RECENT ADVANCES: Many nanocarriers intended
      to exploit redox micro-environments as triggers for drug release, summarized and
      compared in this review, have recently been developed. We describe these
      carriers' chemical structures, strategies for payload protection and oxidation
      selective release, and ROS/RNS sensitivity as tested in initial studies. CRITICAL
      ISSUES: ROS/RNS are unstable, so reliable measures of their concentrations in
      various conditions are scarce. Combined with the dearth of materials shown to
      respond to physiologically relevant levels of ROS/RNS, evaluations of their true
      sensitivity are difficult. FUTURE DIRECTIONS: Oxidation-responsive nanocarriers
      developed thus far show tremendous potential for applicability in vivo; however,
      the sensitivity of these chemistries needs to be fine tuned to enable responses
      to physiological levels of ROS and RNS.

PMID- 24328824
TI  - Validation of a method for quantifying enzalutamide and its major metabolites in
      human plasma by LC-MS/MS.
AB  - BACKGROUND: Enzalutamide is an androgen receptor inhibitor that targets multiple
      steps in the androgen receptor signaling pathway. Oral enzalutamide was recently
      approved by the US FDA and health authorities in other regions for the treatment
      of patients with metastatic castration-resistant prostate cancer who previously
      received docetaxel. The objective of this study was to validate a method for
      quantification of enzalutamide and its two major metabolites in human plasma.
      RESULTS: The analytes were extracted from plasma by an LLE procedure, separated
      by reversed phase HPLC and detected by MS/MS in positive mode ESI. The
      quantitation range was 0.0200-50.0 ug/ml. CONCLUSION: The method proved to be
      rapid and simple, and met FDA validation criteria.

PMID- 24328825
TI  - Pyruvate kinases have an intrinsic and conserved decarboxylase activity.
AB  - The phosphotransfer mechanism of PYKs (pyruvate kinases) has been studied in
      detail, but the mechanism of the intrinsic decarboxylase reaction catalysed by
      PYKs is still unknown. 1H NMR was used in the present study to follow OAA
      (oxaloacetate) decarboxylation by trypanosomatid and human PYKs confirming that
      the decarboxylase activity is conserved across distantly related species. Crystal
      structures of TbPYK (Trypanosoma brucei PYK) complexed with the product of the
      decarboxylase reaction (pyruvate), and a series of substrate analogues (D-malate,
      2-oxoglutarate and oxalate) show that the OAA analogues bind to the kinase active
      site with similar binding modes, confirming that both decarboxylase and kinase
      activities share a common site for substrate binding and catalysis.
      Decarboxylation of OAA as monitored by NMR for TbPYK has a relatively low
      turnover with values of 0.86 s-1 and 1.47 s-1 in the absence and presence of
      F26BP (fructose 2,6-bisphosphate) respectively. Human M1PYK (M1 isoform of PYK)
      has a measured turnover value of 0.50 s-1. The X-ray structures explain why the
      decarboxylation activity is specific for OAA and is not general for alpha-oxo
      acid analogues. Conservation of the decarboxylase reaction across divergent
      species is a consequence of piggybacking on the conserved kinase mechanism which
      requires a stabilized enol intermediate. 

PMID- 24328826
TI  - Voice identity discrimination and hallucination-proneness in healthy young
      adults: a further challenge to the continuum model of psychosis?
AB  - INTRODUCTION: Auditory hallucinations occur in schizophrenia and also in the
      general population. However, evidence points to differences in the nature and the
      mechanisms of clinical and non-clinical hallucinations, challenging the dominant
      assumption that they represent the same phenomenon. The current study extended
      this evidence by examining voice identity perception in hallucination-prone
      individuals. In schizophrenia, deficiencies discriminating between real
      (external) voices have been linked to basic acoustic cues, but voice
      discrimination has not yet been investigated in non-clinical hallucinations.
      METHODS: Using a task identical to that employed in patients, multidimensional
      scaling of voice dissimilarity judgements was used to examine how healthy
      individuals differing in hallucination-proneness (30 high and 30 low
      hallucination-prone individuals) distinguish pairs of unfamiliar voices. The
      resulting dimensions were interpreted with reference to acoustic measures
      relevant to voice identity. RESULTS: A two-dimensional "voice space", defined by
      fundamental frequency (F0) and formant dispersion (Df), was derived for high and
      low hallucination-prone groups. There were no significant differences in speaker
      discrimination for high versus low hallucination-prone individuals on the basis
      of either F0 or Df. CONCLUSIONS: These findings suggest voice identity perception
      is not impaired in healthy individuals predisposed to hallucinations, adding a
      further challenge to the continuum model of psychotic symptoms.

PMID- 24328827
TI  - The aquaporin 1 C-terminal tail is required for migration and growth of pulmonary
      arterial myocytes.
AB  - Pulmonary arterial smooth muscle cell (PASMC) proliferation and migration are
      important contributors to the vascular remodeling that occurs during development
      of pulmonary hypertension. We previously demonstrated that aquaporin (AQP)1, a
      member of the water channel family of proteins, was expressed in PASMCs and was
      necessary for hypoxia-induced migration; however, the mechanism by which AQP1
      controls this response is unclear. The C-terminal tail of AQP1 contains putative
      calcium (EF-hand) and protein binding sites. Thus, we wanted to explore whether
      the C-terminal tail or the EF-hand motif of AQP1 was required for migration and
      proliferation. Rat PASMCs were isolated from distal pulmonary arteries, and
      proliferation and migration were measured using BrdU incorporation and transwell
      filters, respectively. To deplete AQP1, PASMCs were transfected with AQP1 small
      interference RNA (siRNA) or nontargeting siRNA. Knockdown of AQP1 reduced basal
      proliferation and hypoxia-induced migration and proliferation in PASMCs. In
      subsequent experiments, wild-type AQP1, AQP1 lacking the entire cytoplasmic C
      terminal tail, or AQP1 with a mutation in the EF-hand motif were expressed in
      PASMCs using adenoviral constructs. For all AQP1 constructs, infection increased
      AQP1 protein levels, water permeability, and the change in cell volume induced by
      hypotonic challenge. Infection with wild-type and EF-hand mutated AQP1, but not C
      terminal-deleted AQP1, increased PASMC migration and proliferation. Our results
      suggest that AQP1 controls proliferation and migration in PASMCs and that the
      mechanism requires the C-terminal tail of the protein but is independent of water
      transport or the EF-hand motif. 

PMID- 24328829
TI  - Ultrasmall Sn nanoparticles embedded in nitrogen-doped porous carbon as high
      performance anode for lithium-ion batteries.
AB  - In this Letter, we reported on the preparation and Li-ion battery anode
      application of ultrasmall Sn nanoparticles (~5 nm) embedded in nitrogen-doped
      porous carbon network (denoted as 5-Sn/C). Pyrolysis of Sn(Salen) at 650  degrees
      C under Ar atmosphere was carried out to prepare N-doped porous 5-Sn/C with the
      BET specific surface area of 286.3 m(2) g(-1). The 5-Sn/C showed an initial
      discharge capacity of 1014 mAh g(-1) and a capacity retention of 722 mAh g(-1)
      after 200 cycles at the current density of 0.2 A g(-1). Furthermore, a reversible
      capacity of ~480 mAh g(-1) was obtained at much higher current density of 5 A g(
      1). The remarkable electrochemical performance of 5-Sn/C was attributed to the
      effective combination of ultrasmall Sn nanoparticles, uniform distribution, and
      porous carbon network structure, which simultaneously solved the major problems
      of pulverization, loss of electrical contact, and particle aggregation facing Sn
      anode. 

PMID- 24328828
TI  - Multilayers of fluorinated amphiphilic polyions for marine fouling prevention.
AB  - Sequential layer-by-layer (LbL) deposition of polyelectrolytes followed by
      chemical cross-linking was investigated as a method to fabricate functional
      amphiphilic surfaces for marine biofouling prevention applications. A novel
      polyanion, grafted with amphiphilic perfluoroalkyl polyethylene glycol (fPEG)
      side chains, was synthesized and subsequently used to introduce amphiphilic
      character to the LbL film. The structure of the polyanion was confirmed by FTIR
      and NMR. Amphiphilicity of the film assembly was demonstrated by both water and
      hexadecane static contact angles. XPS studies of the cross-linked and annealed
      amphiphilic LbL films revealed the increased concentration of fPEG content at the
      film interface. In antifouling assays, the amphiphilic LbL films effectively
      prevented the adhesion of the marine bacterium Pseudomonas (NCIMB 2021). 

PMID- 24328831
TI  - Identifying causation: the role of the clinical expert.

PMID- 24328832
TI  - The multiple faces of Dravet syndrome.

PMID- 24328833
TI  - Atypical multifocal Dravet syndrome lacks generalized seizures and may show later
      cognitive decline.
AB  - AIM: To show that atypical multifocal Dravet syndrome is a recognizable,
      electroclinical syndrome associated with sodium channel gene (SCN1A) mutations
      that readily escapes diagnosis owing to later cognitive decline and tonic
      seizures. METHOD: Eight patients underwent electroclinical characterization.
      SCN1A was sequenced and copy number variations sought by multiplex ligation
      dependent probe amplification. RESULTS: All patients were female (age range at
      assessment 5-26y) with median seizure onset at 6.5 months (range 4-19mo). The
      initial seizure was brief in seven and status epilepticus only occurred in one;
      three were febrile. Focal seizures occurred in four patients and bilateral
      convulsion in the other four. All patients developed multiple focal seizure types
      and bilateral convulsions, with seizure clusters in six. The most common focal
      seizure semiology (six out of eight) comprised unilateral clonic activity. Five
      also had focal or asymmetric tonic seizures. Rare or transient myoclonic seizures
      occurred in six individuals, often triggered by specific antiepileptic drugs.
      Developmental slowing occurred in all: six between 3 years and 8 years, and two
      around 1 year 6 months. Cognitive outcome varied from severe to mild intellectual
      disability. Multifocal epileptiform discharges were seen on
      electroencephalography. Seven out of eight patients had SCN1A mutations.
      INTERPRETATION: Atypical, multifocal Dravet syndrome with SCN1A mutations may not
      be recognized because of later cognitive decline and frequent tonic seizures.

PMID- 24328834
TI  - Adolescent onset cognitive regression and neuropsychiatric symptoms associated
      with the A140V MECP2 mutation.
AB  - The phenotype attributed to MECP2 mutations continues to expand. In addition to
      classic and variant Rett syndrome, phenotypes include non-specific intellectual
      disability and autism spectrum disorder in females, and fatal neonatal
      encephalopathy in males. One particular phenotype of parkinsonism, pyramidal
      signs, and neuropsychiatric symptoms (PPM-X) has been described only in males. We
      report on the first female with the A140V MECP2 mutation presenting with late
      onset cognitive regression, pyramidal symptoms, parkinsonism, and bipolar
      symptoms. This finding emphasizes the need to consider MECP2 sequencing in
      females with non-classic Rett phenotypes, particularly those with intellectual
      disability and neuropsychiatric features. 

PMID- 24328835
TI  - Selaginpulvilins A-D, new phosphodiesterase-4 inhibitors with an unprecedented
      skeleton from Selaginella pulvinata.
AB  - Selaginpulvilins A-D (1-4), four new phenols with an unprecedented 9,9-diphenyl-1
      (phenylethynyl)-9H-fluorene skeleton, together with four known selaginellins (5
      8) were isolated from Selaginella pulvinata. Their structures were elucidated by
      spectroscopic analysis and chemical correlation. The structure of 1 was confirmed
      by single-crystal X-ray diffraction. Compounds 1-8 exhibited remarkable
      inhibitory activities (IC50 values in the range of 0.11-5.13 MUM) against
      phosphodiesterase-4 (PDE4), a drug target for the treatment of asthma and chronic
      obstructive pulmonary disease. 

PMID- 24328836
TI  - Severity of hospital-treated self-cutting and risk of future self-harm: a
      national registry study.
AB  - BACKGROUND: Risk assessment forms a key component in self-harm management. Among
      self-harm presentations generally, lethality of an index act is a poor predictor
      of future non-fatal repetition. However, no study has examined whether severity
      of an index self-cutting episode is associated with prospective repetition. AIMS:
      To examine factors associated with severity of self-cutting and in particular the
      association between severity of self-cutting and prospective repetition of self
      harm. METHODS: All index self-cutting presentations to emergency departments in
      Ireland over 5 years were grouped by treatment received and compared on the basis
      of demographic and clinical characteristics. RESULTS: Receiving more extensive
      medical treatment was associated with male gender, being aged more than 15 years,
      and not combining self-harm methods. Receiving less extensive treatment conferred
      a higher risk of prospective 12-month repetition, even after controlling for
      demographic and clinical characteristics. Repeat self-harm presentations by those
      with more severe self-cutting in an index act were less prevalent but were more
      likely to involve high-lethality methods of self-harm. DISCUSSION: The results
      indicate that the already-elevated repetition risk among self-cutting patients is
      further increased for those receiving less extensive wound closure treatment.
      Severity of self-cutting might also affect suicide risk but such an association
      has yet to be examined.

PMID- 24328837
TI  - Romania's drug policy from 2005 to 2012: experiences with implementation.
AB  - Even with the relatively high rate of illicit drug use in Romania, drug
      prevention remains a relatively low political and professional priority. Policies
      focus primarily on the criminalization of drug use rather than on prevention and
      treatment. By studying official Romanian drug policies and legislative documents,
      as well as national and European reports on the state of the ''drug problem,''
      this article focuses on the impact of policy on drug use, treatment, and
      prevention, with an emphasis on the criminalization of drug use and the resultant
      trends and practical impacts. The reported lifetime use of illicit drugs has been
      rising slowly but steadily over the last few years. Contraction of communicable
      diseases among intravenous drug users is also trending upwards. And with the
      emphasis on criminalization of drug use and the accompanying marginalization of
      users, drug-law-related offences are also likely to increase. Unmet needs in drug
      prevention, a declining tendency to seek drug treatment, and an increase in drug
      related deaths are also indicators of the negative effects of the current policy
      on drug use, criminalization, infections, and the lack of effective prevention.
      As Romania continues to face serious financial limitations, evidence-based
      research on drug use is needed; best practice guidelines have to be followed in
      order to improve access to drug prevention, treatment, and harm-reduction
      services. 

PMID- 24328838
TI  - Does substance abuse fall exclusively along the externalizing spectrum?
AB  - The current study tested the hypothesis that substance abuse has features of both
      an internalizing and externalizing disorder. A confirmatory factor analysis (CFA)
      of data from 1,177 adjudicated delinquents supported a three-factor model
      (negative emotionality, fearlessness, and disinhibition) over alternate one- and
      two- (internalizing and externalizing) factor models; a second CFA indicated that
      self-reported offending and substance abuse formed separate dimensions rather
      than a single dimension. Correlating several temperament/personality indicators
      with measures of substance misuse and offending revealed that substance misuse
      was significantly more aligned with the internalizing dimension (i.e., negative
      emotionality) and significantly less aligned with the fearlessness externalizing
      dimension. 

PMID- 24328839
TI  - Does it matter what friends think, say, or do? The role of friends' smoking
      attitudes and behavior for Dutch adolescents' smoking behavior.
AB  - Using stochastic actor-based models for longitudinal network analysis, this study
      examines the role of friends' smoking attitudes and behavior for Dutch
      adolescents' smoking behavior in four secondary schools (N = 875). The data were
      collected in two waves in two small suburban towns under second graders in 2008
      to 2009 by means of a standardized questionnaire. Stochastic actor-based models
      for longitudinal network analysis can control for friendship selection while
      examining the effect of friends' attitudes and smoking behavior on the smoking
      behavior of a student. The findings suggest that friends tend to select each
      other on similar smoking behavior. Influence of friends' smoking behavior seems
      to play no role. In one school, an effect of friends' attitudes towards smoking
      on the smoking behavior is found. The implications for future research are to
      consider attitudes when examining the influence of friendship network on smoking
      behavior. The main limitation of this study lies in the limited sample, which
      makes generalizations to the general population difficult. 

PMID- 24328840
TI  - Race as a moderator of the relationship between distress tolerance and cigarette
      smoking.
AB  - The present study examined the role of distress tolerance (DT) and race in
      relation to cigarette smoking. For this study, between 2008 and 2010, 153 women
      (62.1% White, 37.9% African American) from the Washington, DC metropolitan area
      completed a computerized behavioral DT task and self-reported smoking history.
      Results suggest that low DT (OR = .23, p = .03) and the interaction between DT
      and race (OR = 4.58, p = .05) were significantly related to greater odds of being
      a smoker, such that African American women, but not White women, with low DT were
      at increased risk for being a lifetime smoker. 

PMID- 24328841
TI  - Dual tobacco use among college students: contexts of use, self-perceptions, and
      attitudes toward quitting.
AB  - Aggressive marketing of smokeless tobacco (SLT) appears to have led to an
      increase in dual tobacco use. The current study examines the situational
      contexts, self-perceptions, and cessation attitudes/behaviors that relate to dual
      use. Participants (N = 1,242) at a large, Southwestern university completed a
      self-report measure of demographic and tobacco use variables in 2010. Data were
      analyzed using chi-square and one-way ANOVA techniques. Findings suggest that
      type of tobacco use varies by setting and that dual users are more likely than
      sole users to perceive themselves as regular tobacco users. Limitations and
      implications for future research and interventions are discussed. 

PMID- 24328842
TI  - Why do patients stay in opioid maintenance treatment?
AB  - Opioid maintenance treatment (OMT) successfully improves social functioning and
      leads to an increase of survival rates, by reducing drug-related mortality and
      infections. A region-wide anonymous survey was performed to evaluate subjective
      factors that could potentially contribute to growing numbers of patients in OMT
      in the city of Berlin, Germany. In the survey, performed in 2011, 46 staff
      members and 986 patients participated. Both patients and staff members report
      beneficial effects of OMT on physical and mental health, and reduction of
      criminality. Patients on average consider the detoxification from OMT more
      difficult than from heroin. Staff members underestimate the wish of patients to
      reach abstinence of OMT. We conclude that besides reduced mortality, these
      subjective factors may contribute to a growing number of patients in OMT. No
      financial or material support was received in any phase of the study. 

PMID- 24328843
TI  - Promoting the use of substance use survey data.

PMID- 24328844
TI  - The reliability and validity of the Iranian version of the European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire for patients
      with Bone Metastases: the EORTC QLQ-BM22.
AB  - The aim of the present study was to evaluate the psychometric properties of the
      measure among a sample of Iranian patients with bone metastases. One hundred and
      seventy-seven patients with bone metastases undergoing various treatments were
      recruited from Imam Khomeini Hospital in Tehran to participate in the study. The
      coefficient alpha affirmed internal consistency reliability of the Quality of
      Life Questionnaire for patients with Bone Metastases (QLQ-BM22). This measure
      discriminated well between subgroups of the patients based on performance status
      and responding to treatment. Confirmatory factor analysis confirmed the factorial
      validity of the four hypothesized QLQ-BM22 scales. Patients in this study had a
      similar interpretation of the items on the QLQ-BM22 regardless of gender. All
      scales of the QLQ-BM22 were sensitive to change after treatment over a month's
      follow-up, with the exception of psychosocial aspects. The Persian version of the
      EORTC QLQ-BM22 was highly reliable and is valid for use among patients with bone
      metastases who are undergoing various treatment regimes. 

PMID- 24328845
TI  - Discomfort with homosexuality: a new measure captures differences in attitudes
      toward gay men and lesbians.
AB  - This study describes a creative and psychometrically sound method that allows
      researchers to measure homonegativity at a lower threshold than existing measures
      and to differentiate between homonegativity toward gay men and lesbians. Four
      hundred and thirty-one undergraduate students at a Western comprehensive
      university were asked to respond to a series of vignettes describing situations
      in which heterosexuals sometimes experience discomfort in the presence of
      homosexuals, indicating the degree to which they would feel comfortable or
      uncomfortable. The 12-item Homonegativity as Discomfort Scale (HADS) has adequate
      alpha reliability (.92) as well as good criterion and construct validity.
      Suggestions are made as to how the measure could be employed in research. Testing
      on this sample shows greater discomfort with gay men than with lesbians and
      greater discomfort among men than among women. 

PMID- 24328846
TI  - An experimental study on choroidal neovascularization induced by Krypton laser in
      rat model.
AB  - OBJECTIVE: The purpose of this work was to study the efficacy and safety of
      choroidal neovascularization (CNV) formation induced by Krypton laser in Brown
      Norway (BN) rats, and observe the trend of the change of CNV after laser
      photocoagulation. METHODS: Twenty-five male BN rats were involved in this study.
      Two eyes of one rat without any laser photocoagulation were randomly selected as
      the control group, and the other 48 eyes of 24 rats were selected as the
      experimental group. Eight eyes of four rats were randomly selected to receive the
      examinations of fundus fluorescein angiography (FFA), histopathology, and
      transmission electron microscopy 3, 7, 14, 21, 28, and 56 days after laser
      photocoagulation. RESULTS: After laser photocoagulation, the leakage appeared in
      burns on day 7 (59%), reached the peak on day 21 (84%), (p<0.01), and remained
      stable after day 21, proven by FFA and histopathology (p>0.05). The thickness of
      CNV increased from day 7 to day 21 (p<0.01), and remained stable after day 21
      (p>0.05). CONCLUSIONS: The experimental model of CNV can be successfully induced
      by Krypton laser in rats with a stable, long-lasting, and high success rate.
      After laser photocoagulation, the leakages appear on day 7, reach the peak on day
      21, and remain stable after day 21.

PMID- 24328847
TI  - Oral soft tissue wound healing after laser surgery with or without a pool of
      amino acids and sodium hyaluronate: a randomized clinical study.
AB  - OBJECTIVE: The purpose of this study was to compare secondary intention healing
      of oral soft tissues after laser surgery with and without the use of a compound
      containing amino acids and sodium hyaluronate. BACKGROUND DATA: Sodium
      hyaluronate has been successfully used in medicine to promote healing. It has not
      been studied in the healing of laser-produced wounds. MATERIALS AND METHODS:
      Excisional biopsy was performed in oral soft tissues with a potassium-titanyl
      phosphate (KTP) laser (532 nm, SmartLite, DEKA, Florence, Italy) in 49 patients
      divided into two groups. In the study group (SG), 31 patients received a compound
      gel containing four amino acids and sodium hyaluronate (Aminogam((r)), Errekappa,
      Italy) after laser surgery; in the control group (CG), 18 subjects received no
      treatment involving a drug or gel. Numeric rating scale (NRS) was used to
      evaluate pain experienced after surgery [pain index (PI)]. Using a grid as a
      benchmark and computer software, the lesion area was measured after surgery (T0)
      and after 7 days (T1). A percentage healing index (PHI) was calculated indicating
      healing extension in 7 days. RESULTS: SG cases showed an average PHI of 64.38+/
      26.50, whereas the average PHI in the CG was 47.88%+/-27.84. Mean PI was 2.67+/
      0.96 for SG and 2.75+/-0.86 for CG. A statistically significant difference was
      detected between the groups for PHI (p=0.0447), whereas no difference was
      detectable for PI (p=0.77). CONCLUSIONS: The use of a gel containing amino acids
      and sodium hyaluronate can promote faster healing via secondary intention in
      laser-induced wounds, although it does not seem to affect pain perception.

PMID- 24328849
TI  - Ameliorative effects of Bacopa monniera on lead-induced oxidative stress in
      different regions of rat brain.
AB  - Bacopa monniera is a rejuvenating herb for brain cells enhancing learning and
      cognitive ability. In the present investigation, the ameliorative effects of
      Bacopa monniera were examined against lead-induced oxidative stress in different
      regions of rat brain. Male rats were divided into five groups: control (1000 ppm
      sodium acetate) and exposed (1000 ppm lead acetate) for 4 weeks; DMSA (Meso-2,3
      Dimercaptosuccinic acid)-treated (90 mg/kg body weight/day); Bacopa monniera
      treated (BM) (10 mg/kg body weight/day) and a combination of BM + DMSA for seven
      consecutive days after 4 weeks of lead exposure. After treatment, the whole brain
      was isolated by sacrificing rats and four regions were separated namely
      cerebellum, hippocampus, frontal cortex and brain stem. Results indicated a
      significant (p < 0.05) increase in reactive oxygen species (ROS), lipid
      peroxidation products (LPP) and total protein carbonyl content (TPCC) in
      association with tissue metal content in all the four regions of brain for
      exposed group compared with their respective controls. However, the lead-induced
      ROS, LPP, TPCC and tissue metal content were lowered on treatment with Bacopa
      monniera, almost reaching the control group values in all the above brain regions
      compared to DMSA and a combination therapy. Results suggest that Bacopa monniera
      can mitigate the lead induced-oxidative stress tissue specifically by
      pharmacologic interventions which encompass both chelation as well as antioxidant
      functions.

PMID- 24328848
TI  - Fine-tuning somatostatin receptor signalling by agonist-selective phosphorylation
      and dephosphorylation: IUPHAR Review 5.
AB  - The biological actions of somatostatin are mediated by a family of five GPCRs,
      named sst1 to sst5 . Somatostatin receptors exhibit equally high-binding
      affinities to their natural ligand somatostatin-14 and largely overlapping
      distributions. The overexpression of somatostatin receptors in human tumours is
      the molecular basis for diagnostic and therapeutic application of the stable
      somatostatin analogues octreotide, lanreotide and pasireotide. The efficiency of
      somatostatin receptor signalling is tightly regulated and ultimately limited by
      the coordinated phosphorylation and dephosphorylation of intracellular carboxyl
      terminal serine and threonine residues. Here, we review and discuss recent
      progress in the generation and application of phosphosite-specific antibodies for
      human sst2 and sst5 receptors. These phosphosite-specific antibodies are unique
      tools to monitor the spatial and temporal dynamics of receptors phosphorylation
      and dephosphorylation. Using a combined approach of phosphosite-specific
      antibodies and siRNA knock-down screening, relevant kinases and phosphatases were
      identified. Emerging evidence suggests distinct mechanisms of agonist-selective
      fine-tuning for individual somatostatin receptors. The recently uncovered
      differences in phosphorylation and dephosphorylation of these receptors may hence
      be of physiological significance in mediating responses to acute, persistent or
      repeated stimuli in a variety of target tissues.

PMID- 24328851
TI  - Increased epicardial adipose tissue thickness is linked to aortic stiffness in
      patients with primary hypertension.
AB  - AIMS: In patients with hypertension (HT), increased aortic stiffness is related
      to higher cardiovascular morbidity and mortality. Recent investigations have
      shown that epicardial adipose tissue (EAT) is a new potential cardiometabolic
      risk factor. The aim of our study was to examine the relation between
      echocardiographically measured EAT thickness and aortic stiffness in patients
      with primary HT. METHODS: The study included 144 newly diagnosed and untreated
      essential hypertensive outpatients. Transthoracic echocardiographic EAT thickness
      and aortic stiffness measurements were performed for all study participants.
      Afterwards patients were divided in two groups according to their median EAT
      thickness values. The patients with EAT thickness of < 7 mm were included in
      group 1 and patients with EAT thickness of >= 7 mm were included in group 2.
      RESULTS: Aortic strain and distensibility parameters of group 2 were lower than
      in group 1. The aortic stiffness index of group 2 was found to be higher than
      group 1. Multivariate regression analysis revealed that EAT thickness was the
      only independent variable for all three parameters of aortic stiffness index,
      aortic strain and aortic distensibility. CONCLUSION: In patients with newly
      diagnosed primary HT, increased EAT thickness was significantly linked to
      impaired aortic elastic properties independently of other conventional adiposity
      measurements.

PMID- 24328850
TI  - Suicidal carbon monoxide poisoning by combining formic acid and sulfuric acid
      within a confined space.
AB  - Suicide by inhalation of carbon monoxide produced by mixing formic acid and
      sulfuric acid within a confined space is a rare method of suicide. This method is
      similar to the so-called "detergent suicide" method where an acid-based detergent
      is mixed with a sulfur source to produce hydrogen sulfide. Both methods produce a
      toxic gas that poses significant hazards for death investigators, first
      responders and bystanders. Carbon monoxide is an odorless gas, while hydrogen
      sulfide has a characteristic rotten eggs odor, so the risks associated with
      carbon monoxide are potentially greater due to lack of an important warning
      signal. While detergent suicides have become increasingly common in the USA,
      suicide with formic acid and sulfuric acid is rare with only three prior cases
      being reported. Greater awareness of this method among death investigators is
      warranted because of the special risks of accidental intoxication by toxic gas
      and the possibility that this method of suicide will become more common in the
      future. 

PMID- 24328852
TI  - Nosocomial outbreak of a multiresistant Acinetobacter baumannii expressing OXA-23
      carbapenemase in Spain.
AB  - Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 50
      patients between July 2011 and July 2012 at the University Hospital A Coruna (NW
      Spain). These multidrug-resistant isolates, which belonged to a single clone,
      remained only susceptible to tigecycline, minocycline, and colistin and produced
      the carbapenem-hydrolyzing oxacillinase, OXA-23. This is the first reported
      outbreak of OXA-23-producing A. baumannii isolates in Spain. 

PMID- 24328854
TI  - 4-(N,N-Dimethylamino)pyridine hydrochloride as a recyclable catalyst for
      acylation of inert alcohols: substrate scope and reaction mechanism.
AB  - 4-(N,N-Dimethylamino)pyridine hydrochloride (DMAP.HCl), a DMAP salt with the
      simplest structure, was used as a recyclable catalyst for the acylation of inert
      alcohols and phenols under base-free conditions. The reaction mechanism was
      investigated in detail for the first time; DMAP.HCl and the acylating reagent
      directly formed N-acyl-4-(N',N'-dimethylamino)pyridine chloride, which was
      attacked by the nucleophilic substrate to form a transient intermediate that
      released the acylation product and regenerated the DMAP.HCl catalyst. 

PMID- 24328853
TI  - Is NOX2 upregulation implicated in myocardial injury in patients with pneumonia?
AB  - In the present study, we tested the hypothesis that oxidative stress could be
      implicated in myocardial damage during the acute phase of pneumonia. NOX2
      activation, the catalytic subunit of NADPH oxidase, and high-sensitivity cardiac
      troponin T (hs-cTnT) elevation have been analyzed in two hundred forty-eight
      consecutive patients hospitalized for community-acquired pneumonia. Serum NOX2
      derived peptide (sNOX2-dp), a marker of NOX2 activation, and 8-isoprostaglandin
      F2alpha (8-iso-PGF2alpha), a marker of oxidative stress, were measured upon
      admission; serum hs-cTnT and ECG were measured every 12 and 24 h, respectively.
      One hundred thirty-five patients (54%) showed elevated serum levels of hs-cTnT
      (>0.014 MUg/L). A logistic regression analysis showed sNOX2-dp (p<0.001),
      Pneumonia Severity Index score (p<0.001), renal failure (p=0.024), and ejection
      fraction (p<0.001) as independent predictors of elevated serum levels of hs-cTnT.
      Serum sNOX2-dp was linearly correlated with hs-cTnT (Rs=0.538; p<0.001) and 8-iso
      PGF2alpha (Rs=0.354; p<0.001). The study provides the first evidence of a
      significant association between serum cardiac Troponin T elevation and NOX2
      upregulation in patients with pneumonia. This finding raises the hypothesis that
      NOX2-derived oxidative stress may be implicated in myocardial injury and that its
      inhibition could be a novel therapeutic strategy to limit it.

PMID- 24328855
TI  - Human papillomavirus (HPV) risk factors, vaccination patterns, and vaccine
      perceptions among a sample of male college students.
AB  - OBJECTIVE: To examine human papillomavirus (HPV) vaccination rates, including
      initiation and completion of the vaccine series, and barriers to vaccination in a
      sample of male college students. PARTICIPANTS: Male students between the ages of
      18 and 25 who reported being currently or previously sexually active (N = 735).
      METHODS: A cross-sectional Web-based survey was administered during October 2012
      at a large public university in the northeast United States. Student e-mail
      addresses were obtained from the university after institutional review board
      approval. RESULTS: Although condom use was low and number of lifetime sexual
      partners was high, 93% reported they were not at risk for sexually transmitted
      infections. The college men in the sample had low HPV vaccine awareness,
      knowledge, perceived severity, and perceived susceptibility, and 74% of the
      sample had not obtained the HPV vaccine. CONCLUSIONS: There is a disconnect
      between actual and perceived risks of HPV and barriers to HPV vaccination exist.

PMID- 24328856
TI  - The association between 25-hydroxyvitamin D and mammographic density in healthy
      pre- and postmenopausal women regardless of the menstrual cycle phase: a cross
      sectional study.
AB  - Vitamin D deficiency is a known risk factor of breast cancer. An association
      between vitamin D and breast density has been suggested; however, it remains
      controversial. The aim of this study was to determine the association between
      serum 25-hydroxyvitamin D [25(OH)D] level and mammographic density. Subjects in
      our study included 517 patients who visited the health promotion center of the
      University Hospital. Mammographic density was classified using the American
      College of Radiology, Breast Imaging Reporting and Data System. Analysis of
      variance was performed to clarify the association of serum 25(OH)D level and
      mammographic density, and odds ratio was calculated by ordinal logistic
      regression analysis. The mean serum 25(OH)D level was 14.3 +/- 7.0 ng/mL in all
      subjects. In correlation analysis, weak negative correlation was observed between
      serum 25(OH)D level and mammographic density groups (r = -0.09, P = 0.049).
      However, ordinal logistic regression analysis showed no statistically significant
      association between serum 25(OH)D level and mammographic density (odds ratio:
      0.75, 95% confidence interval: 0.50-1.13). Results of our study showed that there
      is no significant association between serum 25(OH)D level and mammographic
      density. It is thought to be an another mechanism of serum 25(OH)D level on
      breast cancer risk in addition to breast density. 

PMID- 24328857
TI  - Interleukin-32gamma suppresses allergic airway inflammation in mouse models of
      asthma.
AB  - Asthma is a chronic airway inflammatory disease typically associated with T
      helper cell type 2 (Th2) cytokines. IL-32, first reported as an inducer of tumor
      necrosis factor (TNF)-alpha, is an inflammatory cytokine involved in various
      autoinflammatory diseases, viral infection, and cancer-related inflammation.
      However, the role of IL-32gamma in asthma has not been clearly elucidated. In
      this study, the levels of IL-32gamma in sputum from patients with asthma were
      measured by ELISA, and IL-32gamma function was investigated in murine models of
      asthma with human IL-32gamma-overexpressed transgenic (IL-32gamma TG) mice. The
      therapeutic effect of recombinant IL-32gamma (rIL-32gamma) on allergic
      inflammation was also evaluated through bronchoalveolar lavage fluid analysis and
      histopathologic examinations. Sputum IL-32gamma levels from patients with asthma
      were lower than those from healthy control subjects. In an acute mouse model of
      asthma, IL-32gamma TG mice exhibited significantly reduced airway inflammation
      compared with that in wild-type mice. The production of Th1 cytokines, such as
      TNF-alpha and IFN-gamma, and Th2 cytokines, such as IL-4, IL-5, and IL-13, was
      decreased in the lungs of IL-32gammaTG mice. On the contrary, the expression of
      IL-10 and IL-10-producing CD11b(+) monocytic cells was significantly increased in
      the lungs of ovalbumin-sensitized IL-32gamma TG mice. In addition, rIL-32gamma
      treatment revealed a suppressive effect on the airway inflammation in a chronic
      mouse model of asthma. The results of this study suggest that IL-32gamma may have
      a preventive role in the development of allergic airway inflammation and could be
      a potential novel therapeutic target for bronchial asthma. 

PMID- 24328858
TI  - Image-enhanced, chromo, and cap-assisted colonoscopy for improving
      adenoma/neoplasia detection rate: a systematic review and meta-analysis.
AB  - OBJECTIVE: The effectiveness of narrow band imaging (NBI), chromoendoscopy (CE),
      and cap-assisted colonoscopy (CAC) on adenoma detection rate (ADR) has been
      investigated in previous meta-analyses; however, there have been no meta-analyses
      of autofluorescence imaging (AFI) or flexible spectral imaging color enhancement
      (FICE) or i-scan. The aim of this study was to determine whether AFI and FICE/i
      scan was more effective than standard/high-definition white light endoscopy to
      improve ADR and to update previous meta-analyses of NBI, CE, and CAC. DESIGN: A
      systematic review and meta-analysis was conducted. Four investigators selected
      appropriate randomized controlled trials (RCT) using the Preferred Reporting
      Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All RCTs in
      which colonoscopy were performed with AFI, FICE, i-scan, NBI, CE, and CAC were
      included. The risk ratios (RRs) calculated from adenoma/neoplasia detection rate
      were used as the main outcome measurement. RESULTS: A total of 42 studies were
      included in the analysis. Pooled estimates of RR (95%confidence interval [CI])
      using AFI, FICE/i-scan, NBI, CE, and CAC were 1.04 (95% CI: 0.87-1.24) (I2 = 0%)
      (fixed effects model [FEM]); 1.09 (95% CI: 0.97-1.23) (I2 = 5%) (FEM); 1.03 (95%
      CI: 0.96-1.11) (I2 = 0%) (FEM); 1.36 (95% CI: 1.23-1.51) (I2 = 16%) (FEM); and
      1.03 (95% CI: 0.93-1.14) (I2 = 48%) (random effects model [REM]), respectively.
      The pooled estimate of RR (95%CI) using indigo carmine in non-ulcerative colitis
      (UC) patients and methylene blue in UC patients was 1.33 (95% CI: 1.20-1.48) (I2
      = 14%) (FEM) and 2.39 (95% CI: 1.18-4.84) (I2 = 0%) (FEM), respectively.
      CONCLUSION: In contrast to AFI, FICE/i-scan, NBI, and CAC, only CE improves ADR.
      CE with methylene blue, though not NBI, is effective for surveillance of
      neoplasia in chronic UC patients.

PMID- 24328859
TI  - Hypoxia-inducible factors regulate human and rat cystathionine beta-synthase gene
      expression.
AB  - Increased catalytic activity of CBS (cystathionine beta-synthase) was recently
      shown to mediate vasodilation of the cerebral microcirculation, which is
      initiated within minutes of the onset of acute hypoxia. To test whether chronic
      hypoxia was a stimulus for increased CBS expression, U87-MG human glioblastoma
      and PC12 rat phaeochromocytoma cells were exposed to 1% or 20% O2 for 24-72 h.
      CBS mRNA and protein expression were increased in hypoxic cells. Hypoxic
      induction of CBS expression was abrogated in cells transfected with vector
      encoding shRNA targeting HIF (hypoxia-inducible factor) 1alpha or 2alpha.
      Exposure of rats to hypobaric hypoxia (0.35 atm; 1 atm=101.325 kPa) for 3 days
      induced increased CBS mRNA, protein and catalytic activity in the cerebral cortex
      and cerebellum, which was blocked by administration of the HIF inhibitor digoxin.
      HIF-binding sites, located 0.8 and 1.2 kb 5' to the transcription start site of
      the human CBS and rat Cbs genes respectively, were identified by ChIP assays. A
      49-bp human sequence, which encompassed an inverted repeat of the core HIF
      binding site, functioned as a hypoxia-response element in luciferase reporter
      transcription assays. Thus HIFs mediate tissue-specific CBS expression, which may
      augment cerebral vasodilation as an adaptive response to chronic hypoxia.

PMID- 24328860
TI  - Psychosis, agnosia, and confabulation: an alternative two-factor account.
AB  - INTRODUCTION: Theories of delusions which rely on a combination of abnormal
      experience and defective belief evaluation and/ or cognitive bias are the subject
      of an emerging consensus. This paper challenges the validity of these theories
      and constructs a two factor alternative. METHODS: The paper starts by identifying
      the difficulty the current theories have explaining the complex delusions of
      schizophrenia and then, by considering, first, the aetiology of somatopsychotic
      symptoms, and second, the literature on the relationship between confabulation
      and allopsychotic symptoms, demonstrates that the natural solution is to retain
      the experiential factor whilst replacing the second factor with confabulation.
      RESULTS: The paper is then able to demonstrate that the resultant two-factory
      theory can clarify recent work on the aetiological role of autonoetic agnosia and
      on the relationships between confabulation, delusion, and thought disorder.
      CONCLUSIONS: The theory supersedes currently available theories in terms of its
      simplicity, fruitfulness, scope and conservatism and represents an advance in the
      search for unified theory of psychosis.

PMID- 24328861
TI  - The economics of tobacco in Lebanon: an estimation of the social costs of tobacco
      consumption.
AB  - OBJECTIVES: Assess the socioeconomic costs of smoking in Lebanon and understand
      the tobacco market and identify the winners and losers from the Lebanese tobacco
      trade. METHODS: We take a close look at the market for tobacco and related
      markets to identify the main stakeholders and estimate the direct costs and
      benefits of tobacco. We also estimate lower bounds for the costs of tobacco, in
      terms of lost productivity, the cost of medical treatment, lost production due to
      premature death, and environmental damage. The paucity of data means our cost
      estimates are conservative lower bounds and we explicitly list the effects that
      we are unable to include. RESULTS: We identify the main actors in the tobacco
      trade: the Regie (the state-owned monopoly which regulates the tobacco trade),
      tobacco farmers, international tobacco companies, local distributors, retailers,
      consumers, and advertising firms. We identify as proximate actors the Ministries
      of Finance and Health, employers, and patients of smoking-related illnesses. In
      2008, tobacco trade in Lebanon led to a total social cost of $326.7 million (1.1%
      of GDP). CONCLUSION: Low price tags on imported cigarettes not only increase
      smoking prevalence, but they also result in a net economic loss. Lebanese
      policymakers should consider the overall deficit from tobacco trade and implement
      the guidelines presented in the Framework Convention on Tobacco Control to at
      once increase government revenue and reduce government outlays, and save the
      labor market and the environment substantial costs.

PMID- 24328862
TI  - Use of nanoclay platelets in food packaging materials: technical and cytotoxicity
      approach.
AB  - Two organo-modified clays for food contact applications were developed to produce
      hydrophobically modified montmorillonite and hence to obtain better compatibility
      between the biopolymer and the filler (nanoclay). These nanofillers were
      characterised by Fourier transform infrared (FTIR) spectroscopy, X-ray
      diffraction and thermogravimetric analysis (TGA) in order to study their
      composition, structure and thermal stability. The fillers were used to reinforce
      polylactic acid (PLA) bottles, which were characterised using different
      techniques such as mechanical and barrier properties, morphology and thermal
      stability. The results were compared with conventional PLA bottles. The use of
      the modified clay in PLA bottles was found to lead to an improvement in
      mechanical and barrier properties. Finally, cytotoxicity tests were carried out
      with the organo-modified clays using Caco-2 and HepG2 cell lines, with uptake of
      neutral red as a basal cytotoxicity biomarker. 

PMID- 24328863
TI  - Dithiophene-Fused Tetracyanonaphthoquinodimethanes (DT-TNAPs): synthesis and
      characterization of pi-extended quinoidal compounds for n-channel organic
      semiconductor.
AB  - Dithiophene-fused tetracyanonaphthoquinodimethanes (DTTNAPs) were synthesized and
      evaluated as n-channel organic semiconductors. DTTNAPs, regardless of isomeric
      structures and substituents, have low-lying LUMO energy levels (~4.6 eV below the
      vacuum level), suitable for stable n-channel field-effect transistors (FETs)
      under ambient conditions. In fact, alpha-DTTNAP derivatives afforded solution
      processed FETs showing an electron mobility of 10(-3) cm(2) V(-1) s(-1),
      indicating that DTTNAPs are a potential molecular framework for n-channel organic
      semiconductors. 

PMID- 24328864
TI  - Tumor-related epilepsy and epilepsy surgery.
AB  - Tumor-related epilepsy (TRE) is a major etiologic category of epilepsy. TRE is
      heterogeneous, and the epidemiology, pathology, pathophysiology, clinical
      features, treatment, and outcomes vary accordingly. In addition, treatment
      imperatives vary between almost purely epilepsy considerations and those that are
      primarily oncologic. Often, there is no clear separation of imperatives, and
      there is a relatively scant evidence base that underpins management decisions in
      such cases. Given a diverse molecular as well as clinical landscape and the rapid
      pace with which new knowledge accrues, there are relatively few recent literature
      resources on TRE that provide neurologists, neurosurgeons, epileptologists, and
      oncologists with an up-to-date, state-of-the-art review of the field in all of
      its important aspects. The proceedings of the Sixth International Epilepsy
      Colloquium in Cleveland in Ohio, U.S.A., in May 2013 on Tumoral Epilepsy and
      Epilepsy Surgery address, at least in part, several TRE aspects crucial to modern
      epilepsy and oncology practice. 

PMID- 24328865
TI  - Recent aspects of classification and epidemiology of epilepsy-associated tumors.
AB  - Epileptic seizures are frequent manifestations of brain tumors. However, biopsy
      specimens of patients who undergo neurosurgical removal of circumscribed foci to
      control chronic recurrent pharmacoresistant seizures often reveal tumor entities
      that are rare in general brain tumor series. The spectrum of these "long-term
      epilepsy-associated neoplasms" comprises highly differentiated glial and
      glioneuronal tumors that show a benign biologic behavior and clinical course, and
      that rarely relapse. Several entities are well recognizable on the basis of
      histopathologic and immunohistochemical characteristics. An intriguing functional
      aspect of these tumors, sometimes collectively referred to as "epileptomas," is
      their prominent epileptogenicity, which may represent a clinical feature
      indicating rather than causing the generally benign biologic behavior of these
      tumors. A frequent feature of respective neoplasms is their coincidence with
      dysplastic lesions in the vicinity of the tumor itself. The recent advent of new
      molecular markers, including genomic alterations leading to activation of the
      protooncogene BRAF and impaired function of isocitrate dehydrogenase (IDH1),
      provides excellent new tools in the differential diagnosis of low grade brain
      tumors, and provides intriguing implications to further develop the pathogenetic
      concepts of these neoplasms. Despite this progress, a number of tumors from
      patients with chronic epilepsy show combinations of cytologic, histologic, and
      immunohistochemical characteristics that challenge the current neuropathologic
      classification schemes. Attempts are currently ongoing to develop further
      classification schemes. 

PMID- 24328866
TI  - Seizure characteristics and prognostic factors of gliomas.
AB  - Epilepsy in neuroepithelial tumors is highly prevalent. Neurogliomas
      (dysembryoplastic neuroepitheliomas [DNETs] and gangliogliomas) have a seizure
      incidence of 80-100%, low-grade gliomas of 60-85%, and glioblastoma of 30-60%.
      With each type, the appearance of seizures is usually the presenting clinical
      symptom, and with neuroglial tumors often the only clinical sign. Tumor locations
      in the temporal and insular cortex are associated with a higher risk of
      developing epilepsy in both neuroglial tumors and low-grade gliomas. Focal
      seizures with or without alteration of consciousness and/or secondary
      generalization are common. Focal seizures with altered consciousness are present
      in 50-70% of neuroglial tumors, and secondarily generalized seizures in 70% of
      low-grade gliomas. Surgical treatment, particularly gross tumor resection,
      contributes strongly to seizure freedom, especially in neuroglial tumors.
      Refractory epilepsy is more common in low-grade gliomas, occurring in 30-35%.
      Recurrence or worsening of seizures is often associated with tumor recurrence in
      glioblastomas. Translational studies have revealed a strong prevalence of IDH1
      enzyme mutation together with the presence of seizures and long-term survival in
      low-grade gliomas. Disturbances of glutamate metabolism occur both in low-grade
      tumors and glioblastomas, and provide insight into mutual cellular pathway
      abnormalities contributing to both seizure development and tumor growth.
      Likewise, the recent clinical observations on antitumor activity of the
      anticonvulsant valproic acid in glioblastoma now provide promising outlooks on
      single therapies that target both seizures and gliomas. 

PMID- 24328867
TI  - Developmental tumors and adjacent cortical dysplasia: single or dual pathology?
AB  - Developmental tumors often lead to refractory partial seizures and constitute a
      well-defined, surgically remediable epilepsy syndrome. Dysplastic features are
      often associated with these tumors, and their significance carries both practical
      and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to
      the extent of the epileptogenic tissue, then presurgical evaluation and surgical
      strategies should target both the tumor and the surrounding dyslaminated cortex.
      Furthermore, the association has been included in the recently revised
      classification of FCD and the epileptogenicity of this associated dysplastic
      tissue is crucial to validate such revision. In addition to the possibility of
      representing dual pathology, the association of developmental tumors and adjacent
      dysplasia may instead represent a single developmental lesion with distinct parts
      distributed along a histopathologic continuum. Moreover, the possibility that
      this adjacent dyslamination is of minor epileptogenic relevance should also be
      entertained. Surgical data show that complete resection of the solid tumors and
      immediately adjacent tissue harboring satellites may disrupt epileptogenic
      networks and lead to high rates of seizure freedom, challenging the epileptogenic
      relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a
      primary or secondary abnormality and whether dyslaminated cortex in the context
      of a second lesion may produce seizures after complete resection of the main
      lesion is still to be proven. 

PMID- 24328868
TI  - Gene markers in brain tumors: what the epileptologist should know.
AB  - Gene markers or biomarkers can be used for diagnostic or prognostic purposes for
      all different types of complex disease, including brain tumors. Prognostic
      markers can be useful to explain differences not only in overall survival but
      also in response to treatment and for development of targeted therapies. Multiple
      genes with specific types of alterations have now been identified that are
      associated with improved response to chemotherapy and radiotherapy, such as O(6)
      methylguanine methyltranferase (MGMT) or loss of chromosomes 1p and/or 19q. Other
      alterations have been identified that are associated with improved overall
      survival, such as mutations in isocitrate dehydrogenase 1 (IDH1) and/or
      isocitrate dehydrogenase 2 (IDH2) or having the glioma CpG island DNA methylator
      phenotype (G-CIMP). There are many biomarkers that may have relevance in brain
      tumor-associated epilepsy that do not respond to treatment. Given the rapidly
      changing landscape of high throughput "omics" technologies, there is significant
      potential for gaining further knowledge via integration of multiple different
      types of high genome-wide data. This knowledge can be translated into improved
      therapies and clinical outcomes for patients with brain tumors.

PMID- 24328869
TI  - Tumoral epileptogenicity: how does it happen?
AB  - Gliomas are the most frequent primary brain tumors and most glioma patients have
      seizures. The origin and mechanisms of human glioma-related epilepsy are
      multifactorial and an intermix of oncologic and neuronal processes. In this brief
      review, we show that the infiltrated peritumoral neocortex appears to be the key
      structure for glioma-related epileptic activity, which depends on the
      interactions between the tumor per se and the surrounding brain. We shed light on
      the underlying mechanisms from two different "tumorocentric" and
      "epileptocentric" approaches, with a special emphasis on the glioma-related
      glutamatergic and gamma-aminobutyric acid (GABA)ergic changes leading to
      epileptogenicity. Because gliomas use the neurotransmitter glutamate as a "tumor
      growth factor" to enhance glioma cell proliferation and invasion with neurotoxic,
      proinvasive, and proliferative effects, glutamate homeostasis is impaired, with
      elevated extracellular glutamate concentrations. Such excitatory effects
      contribute to the generation of epileptic activity in the peritumoral neocortex.
      GABAergic signaling is also involved both in tumor growth and in paradoxical
      excitatory effects mediated by alterations in neuronal and tumor cell Cl(-)
      homeostasis related to cotransporter changes. Local excitability may also be
      affected by an increase in extracellular K(+) concentration, the alkalization of
      peritumoral neocortex, and alterations of gap-junction functioning. Finally, the
      tumor itself may mechanically affect locally neuronal behavior, connections, and
      networks. Better understanding of glioma-related oncologic and epileptologic
      processes are crucial for development of combined therapeutic strategies, but so
      far, the surgical management of gliomas should comprise a maximally safe surgical
      resection encompassing peritumoral neocortex. 

PMID- 24328870
TI  - Systems biology of human epilepsy applied to patients with brain tumors.
AB  - Epilepsy is a disease of recurrent seizures that can be associated with a wide
      variety of acquired and developmental brain lesions. Current medications for
      patients with epilepsy can suppress seizures; they do not cure or modify the
      underlying disease process. On the other hand, surgical removal of focal brain
      regions that produce seizures can be curative. This surgical procedure can be
      more precise with the placement of intracranial recording electrodes to identify
      brain regions that generate seizure activity as well as those that are critical
      for normal brain function. The detail that goes into these surgeries includes
      extensive neuroimaging, electrophysiology, and clinical data. Combined with
      precisely localized tissues removed, these data provide an unparalleled
      opportunity to learn about the interrelationships of many "systems" in the human
      brain not possible in just about any other human brain disorder. Herein, we
      describe a systems biology approach developed to study patients who undergo brain
      surgery for epilepsy and how we have begun to apply these methods to patients
      whose seizures are associated with brain tumors. A central goal of this clinical
      and translational research program is to improve our understanding of epilepsy
      and brain tumors and to improve diagnosis and treatment outcomes of both. 

PMID- 24328871
TI  - MRI in the diagnosis and management of epileptomas.
AB  - High-resolution magnetic resonance imaging (MRI) is invaluable for identifying
      cerebral tumors that cause epilepsy. Serial voxel-based automated quantitative
      analyses are more sensitive than visual reading for detecting change in a lesion.
      Eloquent cortex can be identified with functional MRI (fMRI), with cautions about
      the precise location and extent of critical cortex. Tractography is useful for
      delineating critical white matter tracks as are MR venography and computerized
      tomography (CT) angiography for displaying veins and arteries. These data may be
      combined into a three-dimensional (3D) multimodal MR data presentation and
      displayed interoperatively to increase the precision and minimize the risk of
      neurosurgical treatment, and for the illustrations. 

PMID- 24328872
TI  - The role of functional imaging in the tumor patient.
AB  - Functional imaging studies complement structural magnetic resonance imaging (MRI)
      in the assessment of patients with brain tumor-associated focal epilepsy. (11)C
      Methionine (MET) and (18) F-fluoro-ethyl-L-tyrosine (FET) are amino acid
      analogues that highlight metabolically active areas in positron emission
      tomography (PET). Ictal single photon emission computed tomography (SPECT) can
      provide information about perilesional areas of seizure onset and early
      propagation. Functional MRI (fMRI) and diffusion tensor imaging (DTI) allow
      noninvasive identification of potentially eloquent motor, sensory, and language
      cortical areas and pathways with an accuracy of 10-15 mm compared to
      electrocortical stimulation (ECS). Repetitive navigated transcranial magnetic
      stimulation (TMS) allows even more precise noninvasive delineation of primary
      motor cortex. Information from functional imaging studies helps in the planning
      of brain tumor biopsies, resections, and the planning of intracranial video
      electroencephalography (EEG) studies.

PMID- 24328873
TI  - Long-term monitoring of brain tumors: when is it necessary?
AB  - Tumors, particularly low grade glioma and glioneuronal tumors, account for 25-35%
      of patients who are undergoing epilepsy surgery for intractable seizures. A
      comprehensive epilepsy evaluation including video-electroencephalography (EEG)
      monitoring is useful for most of these patients, to determine the optimal extent
      of resection for the achievement of seizure-free outcome without causing
      postoperative deficits. Video-EEG monitoring for patients with brain tumor should
      also be considered in specific situations, such as patients with new
      postoperative seizures or advanced tumors with unexplained mental status change. 

PMID- 24328874
TI  - Is an epilepsy presurgical evaluation necessary for mid-grade and high-grade
      brain tumors presenting with seizures?
AB  - Patients with epilepsy caused by mid-grade and high-grade tumors do not usually
      undergo formal presurgical epilepsy evaluations before tumor resection. However,
      a minority of these patients may benefit significantly from just such a
      structured presurgical evaluation especially when seizure freedom or seizure
      reduction is a surgical aim in addition to total tumor resection. Typical cases
      comprise patients with multifocal tumors, tumors with bilateral extension, tumors
      over eloquent cortex, and the need for differentiation of spells of an uncertain
      nature, for example, epileptic versus psychogenic nonepileptic seizures. If they
      are epileptic, the definition of the epileptic lesion versus the epileptogenic
      zone and eloquent cortex can be another reason for monitoring. In addition to
      noninvasive recordings, invasive studies that use subdural or depths electrodes
      can be of special importance in these patients, leading to an exact delineation
      of the epileptogenic zone, usually extending beyond the epileptic lesion, and
      allow safe differentiation of epileptic from eloquent cortex. 

PMID- 24328875
TI  - Invasive EEG studies in tumor-related epilepsy: when are they indicated and with
      what kind of electrodes?
AB  - Patients with tumor-related epilepsy (TRE) represent an important proportion of
      epilepsy surgery cases. Recently established independent negative predictors of
      postoperative seizure outcome are long duration of epilepsy, presence of
      generalized tonic-clonic seizures, and incomplete tumor resection. In temporal
      lobe cases, additional hippocampectomy or corticectomy may further improve
      outcome. Invasive electroencephalography (EEG) recordings (IEEG) may be indicated
      to guide the resection by defining eloquent cortex (EC) or to determine the
      extent of potentially magnetic resonance imaging (MRI)-negative epileptogenic
      tissue. In fact, invasive recordings are reportedly used in up to 10% of patients
      who are undergoing epilepsy surgery for TRE. Following careful consideration of
      the concepts underlying epilepsy surgery, the current use of IEEG, and the
      predictors of outcome in extratemporal and temporal tumors in TRE, we postulate
      the following> (1) In patients with extratemporal TRE, IEEG is necessary only if
      the MRI lesion (and if feasible a rim around it) cannot be completely resected
      because of adjacent or overlapping EC. In these cases, EC should be mapped to
      determine its relationships to the lesion, the irritative, and seizure-onset
      zones in order to maximize the extent of the lesionectomy. (2) In patients with
      nondominant temporal TRE, data suggest that if epileptogenic tumors (ETs) are
      encroaching on mesial temporal structures, if epilepsy duration is long, and
      seizures are frequent and disabling, these structures should be included in the
      resection. (3) In patients with dominant temporal TRE, we suggest leaving the
      mesial structures in place if they are functionally and structurally intact and
      to consider resecting these structures only if they are structurally and
      functionally abnormal. There is insufficient evidence justifying the use of IEEG
      to define the extent of the epileptogenic zone in such cases. This should be
      reserved for cases where an initial lesionectomy has failed. 

PMID- 24328876
TI  - Depths and grids in brain tumors: implantation strategies, techniques, and
      complications.
AB  - Patients with intracranial mass lesions are at increased risk of intractable
      epilepsy even after tumor resection due to the potential epileptogenicity of
      lesional and perilesional tissue. Risk factors for tumoral epilepsy include tumor
      location, histology, and extent of tumor resection. In epilepsy that occurs after
      tumor resection, the epileptogenic zone often does not correspond precisely with
      the area of abnormality on imaging, and seizures often arise from a relatively
      restricted area despite widespread changes on imaging. Invasive monitoring via
      subdural grids and/or depth electrodes can therefore be helpful to delineate
      areas of eloquence and localize the epileptogenic zone for subsequent resection.
      Subdural grids offer excellent contiguous coverage of superficial cortex and
      allow resection using the same craniotomy, facilitating understanding of anatomic
      relationships. Depth electrodes offer superior coverage of deep structures, are
      easier to use in cases where a previous craniotomy is present, are not associated
      with anatomic distortion due to brain shift, and may be associated with a lower
      complication rate. We review the biology of focal postoperative epilepsy and
      invasive diagnostic strategies for the surgical evaluation of medically
      refractory epilepsy in patients who have undergone resection of intracranial mass
      lesions. 

PMID- 24328877
TI  - Resection strategies in tumoral epilepsy: is a lesionectomy enough?
AB  - Resection strategies in patients with tumor-related epilepsy vary from
      lesionectomy to larger epilepsy operations with no consensus on optimal
      approaches. The objective of this study is to use our prior experience in the
      management of these patients, to derive optimal strategies for the surgical
      management of epilepsy related to brain tumors. A prospectively compiled database
      of epilepsy and tumor patients was used to identify patients who underwent
      surgical resection of a neoplasm but then developed epilepsy, or who presented
      with epilepsy and were found to harbor a brain tumor. Seizure frequency,
      histopathology, type of surgical resection, and outcomes were compiled. Of 235
      epilepsy surgery patients and 75 low/intermediate grade glioma surgery patients,
      13 (5.5%) and 21 (28%) patients, respectively, had tumoral epilepsy. Twenty-two
      patients were male and 18 tumors were in the left hemisphere. Tumoral epilepsy
      occurred predominantly in temporal (50%) and perirolandic (26.5%) locations. The
      etiology was WHO grade I tumors in 29%, grade II in 35%, and grade III in 33%. In
      the epilepsy group, following lesionectomy in three and tailored resections in
      the majority, seizure outcomes were Engel class I in all except one case. In the
      tumor group, after the initial operation seven additional resections were
      performed due to seizure recurrence. Outcomes in this group were Engel class 1A
      in 18 patients and 1B, 1C and IIA in 1 patient each. Drawing upon these data, we
      propose a classification of the likely reasons of failure in seizure control in
      patients with tumoral epilepsy. This review reiterates the concept that a
      complete resection of the lesion is the best approach for dealing with tumors
      presenting with epilepsy. Overall excellent outcomes can be accomplished
      following aggressive initial tumor resection, re-resection in the context of
      recurrence, and epilepsy style operations in selected patients with a longer
      history of seizures. 

PMID- 24328878
TI  - Brain mapping in tumors: intraoperative or extraoperative?
AB  - In nontumoral epilepsy surgery, the main goal for all preoperative investigation
      is to first determine the epileptogenic zone, and then to analyze its relation to
      eloquent cortex, in order to control seizures while avoiding adverse
      postoperative neurologic outcome. To this end, in addition to neuropsychological
      assessment, functional neuroimaging and scalp electroencephalography,
      extraoperative recording, and electrical mapping, especially using subdural strip
      or grid-electrodes, has been reported extensively. Nonetheless, in tumoral
      epilepsy surgery, the rationale is different. Indeed, the first aim is rather to
      maximize the extent of tumor resection while minimizing postsurgical morbidity,
      in order to increase the median survival as well as to preserve quality of life.
      As a consequence, as frequently seen in infiltrating tumors such as gliomas,
      where these lesions not only grow but also migrate along white matter tracts, the
      resection should be performed according to functional boundaries both at cortical
      and subcortical levels. With this in mind, extraoperative mapping by strips/grids
      is often not sufficient in tumoral surgery, since in essence, it allows study of
      the cortex but cannot map subcortical pathways. Therefore, intraoperative
      electrostimulation mapping, especially in awake patients, is more appropriate in
      tumor surgery, because this technique allows real-time detection of areas crucial
      for cerebral functions--eloquent cortex and fibers--throughout the resection. In
      summary, rather than choosing one or the other of different mapping techniques,
      methodology should be adapted to each pathology, that is, extraoperative mapping
      in nontumoral epilepsy surgery and intraoperative mapping in tumoral surgery.

PMID- 24328880
TI  - Choosing the tumoral epilepsy surgery candidate.
AB  - The management of epilepsy is an essential clinical issue in many patients with
      brain tumors. Tumoral epilepsy is often drug resistant and is associated with
      poor quality of life. Surgery represents a key therapeutic option in the
      management of patients with refractory tumoral epilepsy, with high rates of
      postoperative seizure freedom, especially when gross total resection can be
      performed. The selection of surgical candidates first requires extrapolation of
      the presumed underlying pathology and its potential for malignant transformation
      from clinical and imaging data, especially MRI characteristics. These data
      determine the decision for surgery, as well as its timing and technical aspects
      in relation to the risk of postoperative deficit. In glioneuronal tumors, where
      seizures are often drug-resistant and risk of malignant transformation is very
      low, epilepsy surgery is usually recommended to alleviate disabling seizures and
      side effects of antiepileptic drugs. However, the risk of postoperative deficit
      may outweigh potential benefits of surgery in tumors located within eloquent
      cortex. This issue is particularly relevant for glioneuronal tumors located
      within the dominant mesial temporal structures in patients in whom seizure
      control might require additional hippocampectomy, associated with a high risk of
      memory decline. In contrast, in patients with low-grade gliomas or aggressive
      brain neoplasms, both the decision to perform surgery and selection of the best
      surgical approach primarily rely on the oncologic imperative rather than
      epileptologic considerations. In these patients, the extent of tumor resection
      correlates with improved survival, progression-free survival, as well as with the
      chances of postoperative seizure control. 

PMID- 24328879
TI  - The medical and surgical treatment of tumoral seizures: current and future
      perspectives.
AB  - Epilepsy surgery represents the main treatment option for epileptogenic brain
      tumors. Scalp video-electroencephalography (EEG) and magnetic resonance imaging
      (MRI) may suffice for defining lesional area and seizure-onset zone in discrete,
      surgically resectable lesions. The choice of timing for surgery requires a
      multidisciplinary evaluation, especially in children, when a "wait and see"
      approach is chosen. Discordant electroclinical and neuroimaging data and an ill
      defined epileptogenic lesion require invasive investigations. A multimodal
      integrated approach may maximize the extent of resection while preserving
      cerebral function in the eloquent cortex. Radical removal of the tumor is the
      most important predictor of seizure freedom. Additional predictors include
      histopathology, age at surgery, duration of epilepsy, and seizure type. Patients
      with brain tumors are highly vulnerable in relation to the frequent drug
      resistance of seizures, the potential interactions between antiepileptic drugs
      (AEDs) and chemotherapeutic agents (CMTs), and the risk of AED-related cognitive
      adverse events (24% higher than in the rest of the epilepsy population), in
      addition to brain damage resulting from tumor itself, surgery, and radiotherapy.
      No robust, randomized, controlled evidence supports the choice of AEDs for the
      treatment of seizures in patients with brain tumors. Newer AEDs have limited or
      no enzyme-inducing profile, prevalent renal excretion, lower plasma protein
      binding and, consequently, fewer interactions with CMTs. Enzyme-inducing AEDs can
      lower serum levels of concomitantly administered CMTs. Class I evidence suggests
      that in patients with brain tumors who do not have a history of seizures,
      prophylactic use of AEDs is neutral or ineffective. 

PMID- 24328881
TI  - Optimizing antiepileptic drug treatment in tumoral epilepsy.
AB  - Between 30% and 50% of patients with brain tumors first present with a seizure,
      and up to 30% more will develop seizures later. Therefore, optimal management of
      these patients requires a rational approach to the use of antiseizure
      medications. Based on current evidence, prophylactic prescription of long-term
      antiepileptic drugs (AEDs) in patients with brain tumors in patients who did not
      present with seizures is not justified. Because of the high risk of recurrence,
      however, AED treatment should be strongly considered after a single seizure
      considered to be due to a tumor. Because of the lack of well-controlled
      randomized trials, the decision on which AED provides the best risk-benefit ratio
      in the individual patient is based mostly on physician's judgment rather than
      sound scientific evidence. In patients who may require chemotherapy, a non-enzyme
      inducing AED is preferred for initial treatment to minimize the risk of drug
      interactions that impact adversely on the outcome of anticancer chemotherapy.
      Several retrospective studies in seizure patients with glioblastoma treated with
      chemotherapy have provided evidence for a moderately improved survival with the
      use of valproic acid, possibly due to inhibition of histone deacetylase. However,
      valproic acid may also increase the hematologic toxicity of antineoplastic drugs,
      presumably by inhibiting their metabolism, and may independently impair
      hemostasis, which is of some concern for patients who require surgical
      intervention. Among newer generation AEDs, levetiracetam has a number of
      advantageous features, including availability of a parenteral formulation, but
      other agents such as gabapentin, lamotrigine, oxcarbazepine, topiramate, and
      zonisamide may also be considered. Potentially more effective treatments
      targeting specific mechanisms of epileptogenesis and ictogenesis are being
      investigated. Resection of the tumor, radiation therapy, or chemotherapy can
      bring refractory seizures under control or prolong the duration of seizure
      freedom, an effect that does not appear to be necessarily related to removal or
      shrinkage of the tumor mass. In patients with a successfully treated tumor and an
      overall good prognosis for long-term survival, gradual discontinuation of AEDs
      may be considered. 

PMID- 24328882
TI  - Chemotherapy and immunotherapy of brain tumors: what the epileptologist must
      know.
AB  - I present an overview of therapy for the most common brain tumors encountered in
      clinical practice if adult patients. Current therapy paradigms and evolving
      therapies are reviewed. The introduction of non-enzyme-inducing antiepileptic
      drugs (NEIADs) has simplified the approach to combined medical treatment of
      epilepsy and brain tumors, but the major interactions between enzyme-inducing
      antiepileptic drugs (EIAEDs) are included, to serve as guidance in selecting
      these medications if they are required. 

PMID- 24328883
TI  - Hypothalamic hamartomas: optimal approach to clinical evaluation and diagnosis.
AB  - Hypothalamic hamartomas (HHs) present a difficult medical problem, manifested by
      gelastic seizures, which are often medically intractable. Although existing
      techniques offer modest surgical outcomes with the potential for significant
      morbidity, the relatively novel technique of magnetic resonance imaging (MRI)
      guided stereotactic laser ablation (SLA) offers a potentially safer, minimally
      invasive method with high efficacy for the HH treatment. We report here on 14
      patients with medically refractory gelastic epilepsy who underwent stereotactic
      frame-based placement of an MR-compatible laser catheter (1.6 mm diameter)
      through a 3.2-mm twist drill hole. A U.S. Food and Drug Administration (FDA)
      cleared laser surgery system (Visualase, Inc.) was utilized to ablate the HH,
      using real-time MRI thermometry. Seizure freedom was obtained in 12 (86%) of 14
      cases, with mean follow-up of 9 months. There were no permanent surgical
      complications, neurologic deficits, or neuroendocrine disturbances. One patient
      had a minor subarachnoid hemorrhage that was asymptomatic. Most patients were
      discharged home within 1 day. SLA was demonstrated to be a safe and effective
      minimally invasive tool in the ablation of epileptogenic HH. Because use of SLA
      for HH is being adopted by other medical centers, further data will be acquired
      to help treat this difficult disorder.

PMID- 24328884
TI  - Epilepsy surgery of focal cortical dysplasia-associated tumors.
AB  - The goal of the present study was to evaluate the clinical characteristics and
      postoperative seizure outcome of epileptogenic tumors associated with focal
      cortical dysplasias (FCDs) compared to both solitary FCD type I and solitary
      tumors. Particular attention is given to FCD type IIIb (tumors associated with
      FCD type I), which have been recently classified as a separate entity. We
      retrospectively reviewed the clinical charts of 1,109 patients who were operated
      on for drug-resistant focal epilepsy, including 492 patients with a histologic
      diagnosis of solitary FCD I and II (83 and 157 cases, respectively), solitary
      tumors (179 cases), and FCD-associated tumors (73 cases, 58 of which met the
      criteria of FCD IIIb of the new International League Against Epilepsy [ILAE]
      classification). The different subgroups were evaluated for clinical
      characteristics and postoperative surgical outcome. Clinical variables and
      postoperative seizure outcome of patients with coexisting tumor and FCDs (FCD
      IIIb and tumor associated FCD II) were similar to those of patients with a
      solitary tumor and differed significantly from patients with solitary FCDs.
      Nevertheless, tumors associated with FCDs are characterized by a striking male
      predominance and a higher seizure frequency as compared to solitary tumors.
      Patients with drug-resistant focal epilepsy secondary to a solitary tumor or with
      a tumor-associated FCD have similar basic clinical presentation and postoperative
      seizure outcome. Nevertheless, the epileptogenic contribution of the associated
      FCDs can be crucial, and it needs to be adequately assessed. The impact of FCD on
      tumor-related epilepsy deserves future research in order to optimize the surgical
      strategies aimed at seizure relief. 

PMID- 24328886
TI  - Dysembryoplastic neuroepithelial tumors: where are we now?
AB  - Dysembryoplastic neuroepithelial tumors (DNTs) belong to the surgically treatable
      long-term epilepsy-associated group of tumors. Based on cortical specimens
      provided through epilepsy surgery at Sainte-Anne hospital, three histologic
      subtypes (simple, complex, and nonspecific) have been described. Electroclinical
      data, imaging, intralesional recordings (stereo-electroencephalography [EEG]) and
      histologic correlations have been recently reviewed in order to assess the
      relationship between the epileptogenic zone (EZ), the tumor, and associated focal
      cortical dysplasia (FCD), and to determine optimal strategy for curing epilepsy.
      Based on a large series (78 patients, 50 male, aged 3-54 years, temporal location
      73%, nonspecific forms 68%), we found similar electroclinical data in all DNT
      subtypes, and demonstrated that magnetic resonance imaging (MRI) features allow
      differentiation of histologic subtypes. Type 1 (cystic/polycystic-like) always
      corresponded to complex or simple forms, whereas type 2 (nodular-like) and type 3
      (dysplastic-like) corresponded to nonspecific forms. It is notable that we
      demonstrated intrinsic epileptogenicity in all cases, but found that the EZ
      differed significantly according to MRI subtype, colocalizing with the tumor in
      type 1 MRI, including perilesional cortex in type 2 MRI, and involving extensive
      areas in type 3 MRI. The main prognostic factors for favorable outcome (83% of
      seizure-free patients) were complete tumor and EZ removal, short epilepsy
      duration, and lack of cortico-subcortical damage. According to these findings,
      surgical resection may be restricted to the tumor in type 1 MRI but should be
      more extensive in other MRI subtypes, especially in type 3 MRI. This MRI-based
      scheme may be helpful for optimal resection in epilepsy due to DNTs. In addition,
      we emphasize that early surgery is crucial in curing epilepsy.

PMID- 24328885
TI  - Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments
      for independent (third stage) secondary epileptogenesis.
AB  - Gelastic seizures associated with hypothalamic hamartomas (HHs) are a
      clinicoradiologic syndrome presenting with a variety of symptoms, including
      pharmacoresistant epilepsy with multiple seizure types, electroencephalography
      (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive
      cognitive deterioration. Surgery in adults provides seizure freedom in only one
      third of patients. The poor results of epilepsy surgery could be explained by an
      extrahypothalamic epileptogenic zone. The existence of an independent, secondary
      epileptogenic area with persistent seizures after resection of the presumably
      primary lesion supports the concept of a "hypothalamic plus" epilepsy.
      "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic
      structural lesion (visible on magnetic resonance imaging [MRI] or on
      neuropathology) or if the former is absent, to a functional alteration with
      enhanced epileptogenic properties due to a process termed secondary
      epileptogenesis. We report two patients with gelastic seizures with HH (gelastic
      seizures isolated or associated with dyscognitive seizures of temporal origin).
      Both patients underwent two-step surgery: first an endoscopic resection of the
      HH, followed at a later time by temporal lobectomy. Both patients became seizure
      free only after the temporal lobectomy. In both cases, neuropathology failed to
      demonstrate a significant structural lesion in the temporal lobe. To our
      knowledge, for the first time, these two cases suggest the existence of
      independent secondary epileptogenesis in humans. 

PMID- 24328887
TI  - Resecting the epileptogenic tuber: what happens in the long term?
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant, neurocutaneous
      disorder causing benign noninvasive lesions in multiple organ systems. Cognitive
      delays and neuropsychiatric disorders such as autism are common. Epilepsy is very
      common and is associated with single or multiple epileptogenic cortical tubers.
      More than half of these individuals will become medically refractory over time.
      For these patients, epilepsy surgery with resection of the epileptogenic tuber or
      tubers not only can render a select patient population seizure-free, but also
      improves IQ and cognitive behaviors over time. 

PMID- 24328888
TI  - Controlled-release injectable microemulsions: recent advances and potential
      opportunities.
AB  - INTRODUCTION: Controlled-release injectable (CRI) formulations hold significant
      value for several indications. However, there have been very few successful
      developments and approvals due to various challenges that include limited polymer
      options, drug-excipient process incompatibility and complex scale-up/validation
      processes. Microemulsion technology, as reviewed in this article, promises to
      resolve many of these challenges. AREAS COVERED: In addition to its development
      and manufacturing advantages, feasibility to engineer microemulsion formulations
      by choosing its constituents and nature of formulation vis-a-vis drug candidate
      demonstrates capability of microemulsion to modulate in-vivo drug release and
      thereby optimize drug pharmacokinetics and pharmacodynamics. This potential of
      microemulsion has been used in a few studies to prolong in vivo drug residence
      time resulting in a more favorable benefit/risk profile for various drugs.
      Virtues of injectable microemulsion, results related to prolonged-release
      injectable microemulsion, impact on drug safety and efficacy and possible
      opportunities have been discussed. A detailed review of research work on
      microemulsions as well as other parenteral controlled-release formulations was
      conducted using PubMed, Science Direct and Google Scholar. EXPERT OPINION: The
      fact that microemulsion formulations administered through subcutaneous or
      intramuscular route would undergo significantly prolonged elimination should be
      leveraged to develop novel CRI drug products. Such products will find enormous
      application for several drug candidates which have poor oral pharmacokinetics
      resulting into poor treatment outcome.

PMID- 24328889
TI  - Business cycles, hypertension and cardiovascular disease: evidence from the
      Icelandic economic collapse.
AB  - BACKGROUND: Business cycles affect people's lives. A growing literature examines
      their effect on health outcomes. The available studies on the relationship
      between ambient economic conditions and cardiovascular health show mixed results.
      They are furthermore limited in their outcome measures, focusing mostly on
      mortality. METHODS: We examined the relationship between economic conditions and
      cardiovascular disease and hypertension, using the Icelandic economic collapse of
      2008. Logit regression analyses are used to examine the relationship between
      economic conditions and the probability of reporting a cardiovascular disease or
      hypertension. We furthermore investigated potential mediators of this
      relationship. The data used come from a health and lifestyle survey carried out
      by the Public Health Institute of Iceland in 2007 and 2009. RESULTS: The crisis
      was positively related to hypertension in males but no statistically significant
      relationship was found for females. The mediation analyses indicated partial
      mediation through changes in working hours and stress level, but negligible
      mediation through changes in income. The male hypertension was, however,
      suppressed by concurrent changes in smoking and body weight. CONCLUSIONS: Only
      examining mortality effects of society-wide economic conditions may understate
      the overall effect on cardiovascular health.

PMID- 24328890
TI  - How to use multi-criteria decision analysis methods for reimbursement decision
      making in healthcare: a step-by-step guide.
AB  - In recent years, the quest for more comprehensiveness, structure and transparency
      in reimbursement decision-making in healthcare has prompted the research into
      alternative decision-making frameworks. In this environment, multi-criteria
      decision analysis (MCDA) is arising as a valuable tool to support healthcare
      decision-making. In this paper, we present the main MCDA decision support methods
      (elementary methods, value-based measurement models, goal programming models and
      outranking models) using a case study approach. For each family of methods, an
      example of how an MCDA model would operate in a real decision-making context is
      presented from a critical perspective, highlighting the parameters setting, the
      selection of the appropriate evaluation model as well as the role of sensitivity
      and robustness analyses. This study aims to provide a step-by-step guide on how
      to use MCDA methods for reimbursement decision-making in healthcare. 

PMID- 24328891
TI  - Effective support for those who are "hard to engage": a qualitative user-led
      study.
AB  - BACKGROUND: Up to 30% of people with mental health problems drop out of contact
      with mental health services with negative implications for continuity of care.
      Services with an assertive outreach approach aim to sustain engagement. AIMS:
      This study explored the perceptions and needs of people often described as "hard
      to engage" in order to understand more about how services can best support them.
      METHODS: This was a service user led qualitative study involving participants
      with serious mental health problems. Interviews were held with 33 people using
      assertive outreach or voluntary sector services and 15 people who had disengaged
      from services. Data were analysed for emergent themes. RESULTS: Relationships
      with staff were central to maintaining engagement with services. Almost all
      participants wanted help for their problems, and preferred services that
      responded to their priorities and offered practical support with everyday living.
      Negative perceptions of inpatient care were common, and a focus on medication put
      many participants off mental health services. Many participants were not
      receiving support for the full range of their complex needs. CONCLUSIONS:
      Difficulties in sustaining engagement with mental health services does not
      necessarily mean that people do not want help. Participants were intolerant of
      service-determined priorities.

PMID- 24328892
TI  - Attributions to sexual minority women's academic success.
AB  - Narratives from 33 sexual minority women were examined to discover what factors
      contributed to their ability to acquire academic success, and what, if any,
      attributions are evident in some sexual minority women's experiences that provide
      the ability to persist and graduate. Coping strategies the participants used to
      gain the resiliency and persistence necessary to acquire academic success are
      discussed. Intrinsic themes were work ethic values, altruism, and self-efficacy.
      Extrinsic themes were mentors, family, and friends. Sexual minority women
      identified the complexity of intrinsic and extrinsic attributions that were used
      to successfully complete a four-year undergraduate degree in the United States. 

PMID- 24328893
TI  - Dual-stimuli-responsive micelle of an ABC triblock copolymer bearing a redox
      cleavable unit and a photocleavable unit at two block junctions.
AB  - The design, synthesis, and study of a new dual-stimuli-responsible ABC-type
      triblock copolymer are reported. Using ATRP and click coupling reaction, the
      prepared copolymer is composed of poly(ethylene oxide) (PEO), polystyrene (PS),
      and poly[2-(dimethylamino)ethylmethacrylate] (PDMAEMA) and features a redox
      cleavable disulfide junction between the PEO and PS blocks as well as a
      photocleavable o-nitrobenzyl linkage between the PS and PDMAEMA blocks. This
      design allows the triblock copolymer to respond to both a reducing agent like
      dithiothreitol (DTT) and UV light, while having the minimum number of stimuli
      reactive moieties in the copolymer structure (two per chain). The disruption of
      the triblock copolymer micelles in aqueous solution was examined under the action
      of either UV light or DTT alone or combined use of the two stimuli. It was found
      that the removal of one type of hydrophilic polymer chains from the water-soluble
      corona of the micelles with a hydrophobic PS core, that is, either redox-cleaved
      PEO or photocleaved PDMAEMA, could only result in a limited destabilization
      effect on the dispersion of the micelles. Severe aggregation of the polymer was
      observed only by applying the two stimuli converting the triblock copolymer onto
      three homopolymers. By monitoring the quenching by aqueous medium of the
      fluorescence of a hydrophobic dye (Nile Red) loaded in the triblock copolymer
      micelles, the effect on the payload release was also investigated of the
      different ways in which the micelles can be disrupted by the stimuli. 

PMID- 24328894
TI  - Factors contributing to the high prevalence of multidrug-resistant tuberculosis
      among previously treated patients: a case-control study from China.
AB  - SETTING: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a serious
      global public health problem. In China, the risk factors for MDR-TB have not been
      systematically evaluated. OBJECTIVE: To identify risk factors associated with MDR
      TB among previously treated patients in China. DESIGN: A case-control study was
      carried out. Cases were selected from previously treated MDR-TB patients who were
      resistant to both isoniazid and rifampin, and controls were selected from
      previously treated TB patients who were sensitive to isoniazid and rifampin (non
      MDR-TB). Information was collected from the registration database and a
      structured questionnaire. RESULTS: A total of 61 cases and 50 controls were
      recruited. A multivariate analysis showed that the family annual per-capita
      income <=7,000 Yuan (odds ratio [OR]=3.238; 95% confidence interval [CI]: 1.270
      8.252), no history of fixed dose combinations (FDCs) in anti-TB treatment
      (OR=4.027; 95% CI: 1.457-11.129), and adverse reactions in the course of TB
      treatment (OR=3.568; 95% CI: 1.402-9.085) were independent predictors of MDR-TB.
      Moreover, among the TB patients who had adverse reactions, quitting the treatment
      was shown as a risk factor for MDR-TB (p=0.009). CONCLUSION: In the control of
      MDR-TB among previously treated patients, lower socioeconomic groups, the
      expanding use of FDCs, and improving adherence to treatment by implementing
      Directly Observed Therapy Short Course-Plus (DOTS-Plus), strictly should become a
      priority that requires strong commitment and collaboration among health
      organizations.

PMID- 24328895
TI  - Characterization of plasmid-mediated beta-lactamases in fecal colonizing patients
      in the hospital and community setting in Spain.
AB  - AIM: Active surveillance of plasmid-mediated beta-lactamase-producing
      Enterobacteriaceae (PMBL-E) in fecal carriers in the hospital and in the
      community setting in a non-outbreak period of time. METHODS: Patients were
      screened for carriage of Enterobacteriaceae resistant to expanded-spectrum
      cephalosporins and PMBL-E were characterized (extended-spectrum-beta-lactamase
      [ESBL], plasmid-mediated AmpC beta-lactamase [pAmpC], and carbapenemases) by PCR
      and sequencing. RESULTS: The prevalence of ESBL and pAmpC carriers was 5.06% and
      0.59%, respectively. Overall, CTX-M-like enzymes were the ESBL dominate enzymes
      (96.15%). The group CTX-M-9 was the most prevalent (81, 54%) [CTX-M-14 (74,
      91.35%), CTX-M-9 (5, 6.17%), CTX-M-24 (1, 1.23%), and CTX-M-27 (1, 1.23%)]
      followed by the group CTX-M-1 (64, 42.67%) [CTX-M-15 (42, 65.63%), CTX-M-1 (13,
      20.31%), CTX-M-32 (8, 12.5%), and CTX-M-3 (1, 1.56%)]. One CTX-M-10, one CTX-M
      59, and three CTX-M-8 were also found. A very small representation of SHV or TEM
      ESBL enzymes was found (3.2% and 0.64%, respectively). pAmpC characterization
      revealed a predominance of CMY-2 (81.25%), followed by DHA-1 (18.75%). We did not
      detect the presence of carbapenemase producers. CONCLUSIONS: The prevalence of
      ESBL-producers from fecal carriers is stable in our area, but colonization by
      pAmpC producers has emerged recently as we have confirmed. Periodic active
      surveillance is useful to identify these human reservoirs and control the
      evolution of PMBL carriage in a community over time.

PMID- 24328896
TI  - PpIX induces mitochondria-related apoptosis in murine leukemia L1210 cells.
AB  - CONTEXT: Protoporphyrin IX (PpIX), a well-known sensitizer that can enhance laser
      light or ultrasound induced cytotoxicity in photodynamic and sonodynamic therapy.
      However, PpIX alone could effectively cause anti-tumor effect and the underlying
      mechanisms are rarely been reported. Therefore, this study was to investigate the
      possible mechanism by which PpIX revealed anti-proliferative effect on murine
      leukemia L1210 cells. MATERIALS AND METHODS: The accumulation of PpIX in L1210
      cells and normal peripheral blood mononuclear cells (PBMCs) was evaluated with
      flow cytometry. The subcellular localization of PpIX and apoptosis-inducing
      factor (AIF) translocation were determined by confocal microscope. The cell
      viability was examined by MTT assay. Annexin V-PE/7-AAD and DAPI staining were
      used to detect apoptotic cells. The mitochondrial membrane potential (MMP)
      changes were tested by rhodamine123 staining. DNA damage was measured by comet
      assay. RESULTS: PpIX preferentially accumulated in L1210 cells compared to PBMCs
      and PpIX mainly located in the mitochondria of L1210 cells. PpIX at a
      concentration of 1 ug/ml or above exerted significant anti-tumor effect and the
      cell viability loss presented PpIX dose-dependent manner. Typical apoptotic
      features such as chromatin condensation were observed by DAPI staining. Annexin V
      PE/7-AAD analysis showed 5 ug/ml PpIX could induce about 24% cell apoptosis,
      which was inhibited by cyclosporin A (CsA), an inhibitor of mitochondrial
      permeability transition pore. In addition, the PpIX caused MMP loss, AIF
      translocation to nucleus and serious DNA damage were also suppressed by CsA.
      CONCLUSION: The results indicate mitochondria-dependent apoptosis were involved
      in PpIX caused cell damage on L1210 cells.

PMID- 24328897
TI  - Pneumomediastinum and soft tissue emphysema in pediatric hanging.
AB  - Postmortem computed tomography (CT) is increasingly being used as a tool in
      forensic pathology. The exact value of postmortem imaging in detecting specific
      conditions has not yet been established, but in specific cases, it can be used as
      a diagnostic tool demonstrating findings that remain undetected during autopsy,
      as in this case. Pneumomediastinum and soft tissue emphysema were detected with
      postmortem CT in a 3-year-old girl after hanging. It was not found during
      autopsy. This radiological finding matches 3 adult cases previously described. It
      is assumed that in this case, the first reported in a child, hanging was the most
      likely cause as well. In the adult cases, it was interpreted as a vital sign; the
      person must have been alive to create a pressure gradient causing rupture of the
      alveoli. This case demonstrates one of the added values of postmortem imaging,
      the possibility of demonstrating findings that remain undetected during autopsy. 

PMID- 24328898
TI  - Treatment of proximal interphalangeal joint fractures by the pins and rubbers
      traction system: a follow-up.
AB  - A fracture of the proximal interphalangeal (PIP) joint at the base of the middle
      phalanx is rare, but is a challenge to treat. Posttraumatic osteoarthritis is a
      known complication causing impaired hand function and disability. The aim of the
      present retrospective study was to evaluate characteristics and outcome of
      complex PIP joint fractures treated by the pins and rubbers traction system
      (PRTS). Medical records of 42 patients with fractures treated with a PRTS in 1999
      2010 were reviewed, and followed-up by questionnaires (QuickDASH, CISS, self
      composed questionnaire). Eighteen of the 42 were clinically examined. The
      fractures were divided into three types of fractures: volar lip, dorsal lip, and
      pilon fractures. The volar lip fracture was most frequent (26/42; dorsal lip
      3/42; pilon 13/42). Most fractures were sport-related (19/42; 45%) and males
      predominated (M:F ratio = 1.8). All fractures united. Infection occurred in 17/41
      (41%) cases. Radiological signs of posttraumatic osteoarthritis were found in
      25/41 (61%) patients. In 18/42 patients, where a clinical evaluation was
      performed, 66% of contralateral total active range of motion (TAM), 93% grip
      strength, and 100% pinch strength were achieved. The volar lip fracture had the
      best outcome according to the self-reported QuickDASH and CISS score and regained
      77% of contralateral TAM. Fractures of the PIP joint in the middle phalanx can be
      treated with the PRTS, but reduced mobility, grip strength, infection, and
      osteoarthritis are seen. The device is well tolerated by the patients, easy to
      apply, and with ready accessible materials for the surgeon.

PMID- 24328899
TI  - Reliability of plastic cups to measure breast volume.
AB  - Breast volume measurement is valuable in clinical practice, and various methods
      have been used. Nonetheless, no commonly accepted standard technique exists for
      clinical everyday use and there is no optimal method that is quick, cheap,
      minimally invasive, and acceptable for the patient and for the surgeon.
      Previously, a study has shown that the volume measured with plastic cups differed
      little from that measured from mastectomy specimens. The aim of the present study
      was to test the reliability of breast volume measurements with plastic cups as a
      tool to measure breast volume in everyday clinical practice. The plastic cups
      were designed by the senior author (AR) and comprise 14 cups from 125 millilitres
      (ml) to 2000 ml. Six raters measured 12 breasts on the same day. The results show
      that there is a certain variation between different raters, and that a certain
      rater seems to consistently measure slightly lower or higher volumes than the
      other raters. The Intra Class Correlation (ICC) coefficient of average measures
      between raters is 0.89, that is, the agreement between different raters is high.
      According to the Bland-Altman plot, the overall assessment of the comparisons of
      measurements between the different raters shows that the direction of the mean
      differences is close to zero. The limits of agreements of the differences were
      within +/-56 ml. The coefficient of variation (CV) between different raters was
      14%. Breast volume measurement with plastic cups is an easily usable quick and
      cheap way to measure breast volume in everyday clinical practice. The
      measurements have an acceptable reliability.

PMID- 24328900
TI  - Psychosocial conditions in adults with Crouzon syndrome: a follow-up study of 31
      Swedish patients.
AB  - Crouzon syndrome presents with craniosynostosis, maxillary hypoplasia,
      exophtalmus, and sometimes hampered neuropsychological development. The aim of
      the present study was to evaluate the quality of life for adult patients with
      Crouzon syndrome. Forty patients with Crouzon syndrome born before 1990 could be
      identified. A questionnaire addressing education, employment, social relations,
      and quality-of-life was used. A matched control group was created for comparison.
      Logistic regression, correcting for the influence of age and sex, was used to
      compare patients and controls. Thirty-one patients and 285 controls answered the
      questionnaire. The level of education was lower in patients than in controls (p <
      0.015). Patients were less often married or had a partner (p = 0.059), had fewer
      children of their own (p = 0.004), and had less experience of a sexual
      relationship (p < 0.001). The difference in housing was not significant, and only
      one patient lived in a care centre and three patients required a personal
      assistant to manage activities of daily living. The patients' estimation of their
      somatic health was equal to that of the controls, but the patients more often
      used anti-epileptic medication (p = 0.003). Periods of depressive mood were more
      common in patients (p = 0.001), but there was no difference between the groups
      regarding a general positive attitude to life. In conclusion, patients with
      Crouzon syndrome often have intellectual and social shortcomings that negatively
      affect their lives. However, the range of abilities is wide in this group.

PMID- 24328901
TI  - Sentinel node biopsy (SNB) in malignant melanoma as same day procedure vs delayed
      procedure: clinical and economic outcome.
AB  - The aim of this study was to compare a delayed sentinel node biopsy (dSNB)
      procedure with a same-day procedure (sSNB) in malignant melanoma. In March 2012,
      Aarhus University Hospital went from the dSNB to the sSNB procedure defined by
      lymphoscintigraphy (LS) and sentinel node biopsy (SNB) performed on the same day.
      Before that time, LS was performed 24 hours prior to SNB. The aim was to
      investigate whether differences between the two procedures exist. Patients who
      underwent the SNB procedure between April and July 2011 and 2012, respectively,
      were included in the study. The criteria for SNB were malignant melanoma
      thickness >1 mm, Clark level IV/V, and ulcus or unknown thickness of the
      melanoma. All patients underwent re-excision and SNB at the same time.
      Pathological evaluation was not changed in the observation periods; however, the
      LS procedures varied. Only a minor turnover among the surgeons was observed. One
      hundred and eight patients were included in the study, 59 (dSNB) from 2011 and 49
      (sSNB) from 2012, respectively. A median of 2.17 (dSNB) and 2.31 (sSNB) SLNs were
      removed, with no statistical differences. No difference in node positivity rates
      was observed. However, the number of hospitalisation days differed significantly,
      with 1.94 days in dSNB and 0.49 days in sSNB. Rates of complications at the site
      of the SNB procedure were similar. No differences in disease-free survival (DFS)
      or overall survival (OS) were recorded. SNB does not increase the overall
      survival. It is, therefore, essential to keep the morbidity and economic costs
      low, while keeping the quality of the procedure high.

PMID- 24328902
TI  - A 30-day risk assessment of mastectomy alone compared to immediate breast
      reconstruction (IBR).
AB  - Immediate breast reconstruction (IBR) is emerging as a favourable reconstruction
      option for breast cancer patients. Understanding the factors associated with
      complications following IBR will enhance care delivery, risk counselling and
      management, and potentially improve patient satisfaction. Women undergoing
      mastectomy alone and mastectomy with IBR from 2005-2011 were identified in the
      ACS-NSQIP datasets. Specific complications examined included surgical (flap or
      prosthesis loss and unplanned reoperation), wound (superficial/deep surgical site
      infection and wound dehiscence), and medical complications. Bivariate and
      multivariate analyses were performed to identify predictors of outcomes. A total
      of 47,443 patients were identified. For patients who underwent IBR compared to
      mastectomy alone, total complications (11.2% vs 9.2%, p < 0.001) and surgical
      complications (7.8% vs 4.7%, p < 0.001) were more frequent. In adjusted analysis,
      a common predictor of complications was class III obesity (BMI >= 40 kg/m(2)) for
      mastectomy alone (OR = 1.79, p < 0.001) and implant-based IBR (OR = 2.20, p <
      0.001), and class II obesity (BMI 35-39.9) for autologous IBR (OR = 1.62, p =
      0.003). Wound complications were found to be associated with autologous
      reconstruction (p < 0.001 kg/m(2)), smoking (p < 0.001), bilateral procedures (p
      = 0.005), patient comorbidity (p = 0.006), obesity (p < 0.001), and diabetes (p <
      0.001). The strongest predictors of wound complications were class II obesity (OR
      = 2.12), class III obesity (OR = 3.09), and smoking (OR = 1.70). Risk factors for
      medical morbidity included: immediate autologous (p < 0.001), recent chemotherapy
      (p = 0.013), ASA physical status (p < 0.001), bilateral procedure (p = 0.002),
      patient comorbidity (p < 0.001), and obesity (p < 0.001). The strongest
      predictors of medical morbidity were immediate autologous reconstruction (OR =
      3.54) and comorbidity burden of >=2 comorbid conditions (OR = 2.28). In
      conclusion, undergoing IBR is associated with a modality-specific increased risk
      of morbidity relative to mastectomy alone. However, other modifiable risk factors
      appear to be strongly correlated with postoperative complications. LEVEL OF
      EVIDENCE: prognostic/risk category, level II.

PMID- 24328903
TI  - Reconstruction of severe medial orbital wall fractures using titanium mesh plates
      by the pericaruncular approach.
AB  - Medial orbital wall fractures can cause severe aesthetic and functional
      complications, if not treated properly. The aim of this study was to
      prospectively evaluate the use of titanium mesh plates inserted through the
      pericaruncular approach for the treatment of medial orbital wall fractures.
      Between 1 July 2010 and 1 January 2013, a total of 17 patients with large medial
      orbital wall defects were treated. All of the large bony defects were treated
      using titanium mesh plates inserted through the pericaruncular approach. All
      patients had anatomically correct orbital wall reconstruction as accessed by
      immediate postoperative computed tomography scan. One patient with large bony
      defects presented with diplopia after the primary procedure. Re-operation was
      needed for correction. After surgery, the diplopia was corrected. In all
      patients, postoperative morbidity was minimal and cosmetic results were
      excellent. Titanium mesh may be a valuable material for the reconstruction of
      severe medial orbital wall defects. Its advantages include excellent structural
      support, shorter operative time, and ease of being moulded into the desired
      shape. The pericaruncular approach may allow for or give direct access to the
      medial orbital wall and orbital apex without any cutaneous incision or disruption
      of the medial canthal ligament, and insertion of titanium mesh plates is possible
      under direct vision. It is proposed that this technique could be advantageous in
      the reconstruction of severe medial orbital wall fractures.

PMID- 24328904
TI  - Effects of a recreational ice skating program on the functional mobility of a
      child with cerebral palsy.
AB  - PURPOSE: The purpose of this study was to describe the effects of an ice skating
      program on the ambulation, strength, posture and balance of a child with cerebral
      palsy (CP). DESCRIPTION: The subject was a five-year-old female with a diagnosis
      of CP and a Gross Motor Classification System level of III. The subject was a
      slow and labored household ambulator on level surfaces with bilateral forearm
      crutches and bilateral ankle foot orthoses. She was unable to transfer to and
      from the floor to stand independently, stand unsupported or take steps
      independently. Until the initiation of this study she was receiving physical
      therapy services 2*/week. For the purpose of this study she participated in a 1
      h/week local ice skating program for people with disabilities for a period of
      four months. OUTCOMES: The subject displayed clinically significant improvements
      in functional mobility including: improved standing posture; independent transfer
      to and from the floor to stand; maintenance of independent standing for 3 min;
      independent walking for 10 feet; increased ability to isolate extremity
      musculature; increased strength; improved Gross Motor Function Measure-88 scores
      and increased endurance. A subsequent testing session four months after the ice
      skating program had ended displayed declines but not to pre-intervention levels
      in muscle strength; ability to transfer to and from the floor to stand;
      functional mobility and standing balance. DISCUSSION: The results appear to
      suggest that the participation in an ice skating program clinically improved this
      child's functional mobility. Further research needs to be done with regard to
      physical recreational programs and the benefit they can have on the function of
      children with activity limitations.

PMID- 24328905
TI  - A narrative reasoning course to promote patient-centred practice in a
      physiotherapy undergraduate programme: a qualitative study of final year
      students.
AB  - BACKGROUND: Narrative reasoning has been presented as a core component of the
      health professionals' competencies. AIM OF THE STUDY: This study aimed to explore
      the students' perspectives about the contribution of a narrative reasoning course
      to promote patient-centred practice. METHODS: An interpretative phenomenological
      analysis (IPA) was undertaken through focus groups. Eighteen volunteer final year
      students participated in three focus groups. Data analysis followed the IPA
      principles. FINDINGS: Three themes emerged: (1) "developing distinctive
      competencies"; (2) "shifting students' focus" and (3) "challenging students'
      professional identity". In the first theme, students distinguished their
      capability to better understand patients' experiences and needs and to be aware
      of the importance of a collaborative therapeutic relationship. In the second
      theme, students emphasized a shift from themselves as clinicians towards their
      patients. Finally, in the third theme participants shared the perspective that
      they have developed a different clinical profile, and that their reasoning and
      clinical actions have changed. CONCLUSIONS: Students recognized the contribution
      of the course in developing competencies to facilitate patient-centred practice.
      Future research is needed to inform lecturers on how to best integrate narrative
      reasoning within the physiotherapy undergraduate curricula.

PMID- 24328906
TI  - Gender differences in college leisure time physical activity: application of the
      theory of planned behavior and integrated behavioral model.
AB  - OBJECTIVE: National data consistently report that males participate in leisure
      time physical activity (LTPA) at higher rates than females. This study expanded
      previous research to examine gender differences in LTPA of college students using
      the theory of planned behavior (TPB) by including 2 additional constructs,
      descriptive norm and self-efficacy, from the integrated behavioral model.
      PARTICIPANTS: Participants were college students (N = 621) from a large public
      university in the southeastern United States. METHODS: A self-report, classroom
      based assessment with validated and reliable measures of LTPA, TPB constructs,
      descriptive norm, self-efficacy, and demographics was conducted in fall 2009.
      RESULTS: Regression analyses revealed attitude (beta = .119), intention (beta =
      .438), self-efficacy (beta = .166), body mass index (BMI) (beta = -.084), and
      sports participation (beta = .081) as significantly associated with LTPA for
      females (R (2) = .425, p < .001), whereas intention (beta = .371) was significant
      for males (R (2) = .202, p < .001). CONCLUSIONS: Practitioners should consider
      tailoring promotional materials to address these gender differences in efforts to
      increase LTPA participation among college students.

PMID- 24328907
TI  - The effect of tacrolimus compared with betamethasone valerate on the skin barrier
      in volunteers with quiescent atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease arising as a
      result of immune system and skin barrier defects. Topical corticosteroids are
      safe and effective treatments for AD, when used in short courses. Prolonged use
      is associated with skin barrier damage. Topical calcineurin inhibitors are
      alternative immune-modulating treatments for AD purported to have no negative
      effects on the skin barrier. OBJECTIVES: To compare the effects of betamethasone
      valerate 0.1% cream (BMVc) and tacrolimus 0.1% ointment (TACo) on the skin
      barrier. METHODS: Twenty volunteers with quiescent AD (no active signs for 6
      months) participated in a randomized observer-blind study, wherein BMVc was
      applied to one forearm and TACo to the other, twice daily for 4 weeks. The
      biophysical/biological properties of the stratum corneum were assessed before and
      after treatment. Nine volunteers with active disease and 10 with healthy skin
      were assessed at untreated sites. RESULTS: BMVc significantly reduced skin
      barrier function, integrity and cohesion, and the levels of pyrrolidone
      carboxylic acid (PCA) and urocanic acid (UCA) towards the subclinical barrier
      defect observed in patients with AD (nonlesional sites). TACo preserved skin
      barrier function, integrity, cohesion and PCA and UCA levels, while significantly
      increasing skin hydration to levels comparable with healthy skin. Both treatments
      reduced skin surface pH and trypsin-like protease activity, with TACo doing so to
      a significantly greater degree. CONCLUSION: In quiescent AD, 4 weeks of BMVc
      treatment adversely affected the biophysical properties of the skin and reduced
      the levels of natural moisturizing factor, whereas TACo improved the condition of
      the skin barrier.

PMID- 24328909
TI  - Prevalence of hypercoagulable disorders in inflammatory bowel disease.
AB  - OBJECTIVE. Inflammatory bowel disease (IBD) can be associated with
      hypercoagulable disorders. Aim of this single-center, prospective study was an in
      depth evaluation of acquired hypercoagulable states in IBD patients. METHODS. A
      total of 110 patients with Crohn's disease (CD) (aged 19-69; mean 40.5, median
      38.5 years), 43 with ulcerative colitis (UC) (aged 17-72; mean 42, median 36
      years), and 30 controls were enrolled. Full blood count, serum C-reactive protein
      (CRP), proteins C and S, activated protein C (APC) resistance, thrombin
      antithrombin complex (TAT), F1+F2 fragments, tissue factor pathway inhibitor
      (TFPI) total and truncated, TFPI-factor Xa, tissue plasminogen activator (tPA)
      and PAI-I antigen were investigated in peripheral blood samples. RESULTS. Only 18
      of 153 (11.8%) IBD patients had hemocoagulation parameters within normal range.
      Significant difference between IBD patients and controls was found in thrombocyte
      volume (p < 0.001), protein C (p = 0.025), protein S (p = 0.003), APC resistance
      (p < 0.001), F1+F2 fragments (p < 0.001), and tPA (p = 0.002). In CD patients who
      were divided into two subgroups according to serum CRP values (non-active
      disease: <5 mg/L; active disease >=5 mg/L), thrombocyte count was significantly
      lower (p = 0.001), thrombocyte volume was significantly higher (p = 0.002), F1+F2
      fragments were significantly lower (p = 0.007) and tPA was significantly higher
      (p = 0.038) in the subgroup with CRP <5 mg/L. In UC patients, no significant
      difference depending on CRP was found. CONCLUSIONS. Acquired hypercoagulable
      abnormalities in IBD patients are frequent. Patients with active CD, but not UC,
      displayed significantly different hemocoagulable parameters, when compared to non
      active CD/UC subjects. In patients with active CD (with increased serum CRP
      concentration) and patients with active extensive UC found at endoscopy (despite
      low CRP values), prophylactic anticoagulation therapy should be considered.

PMID- 24328908
TI  - Mechanism of cytotoxic action of crambescidin-816 on human liver-derived tumour
      cells.
AB  - BACKGROUND AND PURPOSE: Marine sponges have evolved the capacity to produce a
      series of very efficient chemicals to combat viruses, bacteria, and eukaryotic
      organisms. It has been demonstrated that several of these compounds have anti
      neoplastic activity. The highly toxic sponge Crambe crambe has been the source of
      several molecules named crambescidins. Of these, crambescidin-816 has been shown
      to be cytotoxic for colon carcinoma cells. To further investigate the potential
      anti-carcinogenic effect of crambescidin-816, we analysed its effect on the
      transcription of HepG2 cells by microarray analysis followed by experiments
      guided by the results obtained. EXPERIMENTAL APPROACH: After cytotoxicity
      determination, a transcriptomic analysis was performed to test the effect of
      crambescidin-816 on the liver-derived tumour cell HepG2. Based on the results
      obtained, we analysed the effect of crambescidin-816 on cell-cell adhesion, cell
      matrix adhesion, and cell migration by Western blot, confocal microscopy, flow
      cytometry and transmission electron microscopy. Cytotoxicity and cell migration
      were also studied in a variety of other cell lines derived from human tumours.
      KEY RESULTS: Crambescidin-816 had a cytotoxic effect on all the cell lines
      studied. It inhibited cell-cell adhesion, interfered with the formation of tight
      junctions, and cell-matrix adhesion, negatively affecting focal adhesions. It
      also altered the cytoskeleton dynamics. As a consequence of all these effects on
      cells crambescidin-816 inhibited cell migration. CONCLUSIONS AND IMPLICATIONS:
      The results indicate that crambescidin-816 is active against tumour cells and
      implicate a new mechanism for the anti-tumour effect of this compound.

PMID- 24328911
TI  - Green tea consumption and incidence of colorectal cancer.

PMID- 24328910
TI  - The thioredoxin system in neonatal lung disease.
AB  - SIGNIFICANCE: Fetal lung development takes place in hypoxia meaning that
      premature birth is hyperoxia for the prematurely born infant. The most common
      respiratory morbidity afflicting premature infants is bronchopulmonary dysplasia
      (BPD). Pathophysiologically, BPD represents the impact of injury, including O2
      toxicity, to the immature developing lung that causes arrested lung development.
      RECENT ADVANCES: The thioredoxin (Trx) system, which is predominantly expressed
      in pulmonary epithelia in the newborn lung, acts as an antioxidant system;
      however, it is increasingly recognized as a key redox regulator of signal
      transduction and gene expression via thiol-disulfide exchange reactions. CRITICAL
      ISSUES: This review focuses on the contribution of Trx family proteins toward
      normal and aberrant lung development, in particular, the roles of the Trx system
      in hyperoxic responses of alveolar epithelial cells, aberrant lung development in
      animal models of BPD, O2-dependent signaling processes, and possible therapeutic
      efficacy in preventing O2-mediated lung injury. FUTURE DIRECTIONS: The
      significant contribution of the Trx system toward redox regulation of key
      developmental pathways necessary for proper lung development suggests that
      therapeutic strategies focused on preserving pulmonary Trx function could
      significantly improve the outcomes of prematurely born human infants.

PMID- 24328912
TI  - Upper airway changes after Xbow appliance therapy evaluated with cone beam
      computed tomography.
AB  - OBJECTIVE: To determine the treatment effects of the Xbow appliance on the upper
      airway dimensions and volume using cone-beam computed tomography (CBCT); to
      evaluate the cephalometric changes in the skeletal and dental structures of the
      skeletal Class II patients. MATERIALS AND METHODS: The sample consisted of 25
      Class II patients (11 male, 14 female) with a mean age of 11.1 +/- 1.1 years.
      CBCT images were obtained at the beginning of the treatment (T0) and after the
      debonding of the Xbow (T1). RESULTS: Changes in superior, middle, and inferior
      parts of the oropharynx in the retroglossal region and changes in the
      oropharyngeal airway volume were statistically significant (P < .05, P < .01).
      The differences favoring the Xbow for the changes in the direction of Class II
      correction included SNA, SNB, ANB, maxillary depth angles, and point A-NPg and Co
      B distances. Data of the dental parameters showed palatal tipping and extrusion
      of the maxillary incisors, labial tipping of the mandibular incisors, and mesial
      movement and extrusion of the mandibular molars. CONCLUSIONS: Treatment with the
      Xbow appliance in Class II patients resulted in favorable increase in the
      oropharyngeal airway dimensions and volume. Further studies with larger study
      samples and with control groups are needed.

PMID- 24328913
TI  - Effect of socioeconomic status on normative and perceived orthodontic treatment
      need.
AB  - OBJECTIVE: To determine the influence of socioeconomic status (SES) on normative
      and perceived orthodontic treatment need, satisfaction with dental appearance,
      and regularity of dental attendance. MATERIALS AND METHODS: The sample consisted
      of 550 adolescents (232 boys, 318 girls) aged 13 to 17 years who were categorized
      according to SES into three groups: low, middle, and high SES. Normative
      treatment need was assessed by using the Index of Orthodontic Treatment Need.
      Data were collected by clinical examination and face-to-face interview. The
      chi(2) test and logistic regression analysis were used for statistical analyses.
      RESULTS: Approximately 34.0% of the untreated subjects had a definite dental need
      for treatment and 24.5% had a moderate need; among those, 53.5% were of low SES
      (P  =  .017). One-third of the sample had a moderate to definite esthetic need,
      most of whom had a low SES (P  =  .009). Of the subjects who were dissatisfied
      with their dental appearance and reported a self-perceived need for treatment,
      around one-third had a low SES. Most subjects with low SES were irregular dental
      attenders (P < .001). Subjects of low SES, those who had a self-perceived need
      for treatment, and those who were dissatisfied with their dental appearance were
      more likely to have a definite normative esthetic need. CONCLUSIONS: Subjects of
      low SES exhibited greater normative and perceived treatment needs than subjects
      of higher SES. They were less satisfied with their dental appearance and visited
      a dentist less frequently.

PMID- 24328914
TI  - Dimercuration of calix[4]arenes: novel substitution pattern in calixarene
      chemistry.
AB  - A mercuration reaction of tetrapropoxycalix[4]arene immobilized in the cone
      conformation gave a mixture of two dimercurated products (meta,meta and
      meta,para) in approximately a 1:1 ratio. Both regioisomers represent inherently
      chiral compounds, which makes them very attractive for design of novel receptors.
      As demonstrated by Pd-catalyzed arylation, the different reactivity of HgCl
      functions in the meta,para-disubstituted isomer opens the door for regioselective
      introductions of two different functional groups to achieve a substitution
      pattern so far unknown in calixarene chemistry. 

PMID- 24328915
TI  - Unsuspected Langerhans cell histiocytosis can be easily missed in a colonic
      biopsy.
AB  - Langerhans cell histiocytosis (LCH) involvement of the gastrointestinal tract
      (GIT) is rare. The infiltrate in a colonic biopsy can be dissimilar to classic
      cytomorphologic features. It could be patchy, restricted to the subepithelial
      lamina propria and the lesional cells might have prominent nucleoli with
      lymphocytes-dominant background. The GIT manifestations could be confused with
      infectious, allergic, immunodeficiency and inflammatory bowel diseases. The
      rarity of GIT lesions, unawareness of some atypical endoscopic and histologic
      features might lead to false negative results. We report a case of LCH in an 11
      month-old baby that was clinically unsuspected and histologically overlooked. 

PMID- 24328916
TI  - Radical route for the alkylation of purine nucleosides at C6 via Minisci
      reaction.
AB  - A highly regioselective Minisci reaction with the decarboxylative alkylation of
      purine nucleosides under mild conditions was developed. With 5 mol % AgNO3 as a
      catalyst and (NH4)2S2O8 as an oxidant, a series of purine nucleosides including
      ribosyl, deoxyribosyl, arabinosyl purine nucleosides worked well with primary,
      secondary, and tertiary aliphatic carboxylic acids. 

PMID- 24328917
TI  - Health and productivity: the occupational and environmental health nurse role.

PMID- 24328918
TI  - Self-care and yoga-academic-practice collaboration for occupational health.
AB  - High rates of stress and burnout among nurses and other health care providers
      justify the exploration of innovative interventions designed to reduce stress and
      promote self-care among this population. A growing body of evidence supports the
      physical and psychosocial benefits of yoga and suggests the potential for yoga to
      support self-care and reduce stress among health care providers. This article
      describes the formation of an academic-practice collaboration to use yoga as a
      model for occupational health and wellness among nurses employed at a tax
      supported urban health system. In addition, recommendations for program
      sustainability over time are discussed.

PMID- 24328920
TI  - Planning for older workers.
AB  - Occupational and environmental health nurses can improve planning for an aging
      workforce by reviewing existing programs and services and adding aging and multi
      generational workforce issues to ongoing training.

PMID- 24328919
TI  - Occupational chemical exposures among cosmetologists: risk of reproductive
      disorders.
AB  - More research is needed to understand possible occupational reproductive risks
      for cosmetologists, specifically hairdressers and nail technicians, two
      occupations that often share workspace and exposure to hair dyes and nail polish.
      Cosmetologists are predominantly females of reproductive age; thus, they may be
      at higher risk for the effects of exposure to reproductive toxins. The purpose of
      this article is to inform nurses and public health professionals about
      occupational exposures for cosmetologists and discuss interventions to reduce the
      risks of reproductive disorders among susceptible worker populations.

PMID- 24328921
TI  - Lp-PLA2 is associated with structural valve degeneration of bioprostheses.
AB  - OBJECTIVES: In this study, we sought to determine the metabolic markers
      associated with structural valve degeneration (SVD). BACKGROUND: Structural valve
      degeneration (SVD) is the major cause of bioprosthetic valve failure leading to
      bioprostheses (BPs) stenosis or regurgitation. We hypothesized that lipoprotein
      associated phospholipase A2 (Lp-PLA2) is involved in the SVD of BPs. METHODS: We
      included 197 patients who underwent aortic valve replacement with a bioprosthetic
      valve and had echocardiographic follow-up to evaluate valve function. Moreover,
      explanted BPs (n = 39) were analysed by immunohistochemistry for the expression
      of Lp-PLA2. RESULTS: After a mean follow-up of 7.9 +/-0.2 years, forty-one
      patients (21%) were identified as developing SVD. Patients with SVD had
      significantly higher plasma level of Lp-PLA2 mass (151.8 +/- 9.2 ng/mL vs. 133.2
      +/- 3.4 ng/mL, P = 0.03) and activity (27.6 +/- 0.9 nmol/min/mL vs. 25.0 +/- 0.4
      nmol/min/mL, P = 0.005). Multivariate analysis revealed that Lp-PLA2 activity
      (OR: 1.09, 95% CI: 1.01-1.18; P = 0.03) was the strongest independent predictor
      of SVD. Immunohistochemistry studies of explanted BP showed that 77% of explanted
      BPs had the expression of Lp-PLA2, which correlated with the density of
      macrophages (CD68), and ox-LDL levels in bioprosthetic tissues. CONCLUSIONS:
      Increased blood plasma activity of Lp-PLA2 is associated with higher prevalence
      of SVD. These findings open new avenues for the identification of patients at
      risk for SVD and for the development of pharmacotherapy aiming at the prevention
      of SVD.

PMID- 24328922
TI  - Novel alternative therapy for spinal tuberculosis during surgery: reconstructing
      with anti-tuberculosis bioactivity implants.
AB  - Accompanied with the worsening of the pulmonary tuberculosis bacterium (TB)
      epidemic, the incidence of spinal TB has increased in recent years. Spinal
      reconstruction and stabilisation, and bone defect repair play a crucial role in
      the surgical treatment of spinal TB. Unfortunately, the existing materials have
      not completely met the requirements for spinal TB reconstruction due to their
      diverse deficiencies. Therefore, there is an urgent need to develop novel
      reconstructing implants. Poly-DL-lactide (PDLLA) and nano-hydroxyapatite (nHA)
      are two promising drug delivery systems (DDS) and materials for bone repair,
      which could help us to overcome the difficulties in spinal TB reconstruction in
      the future. In this article, we discuss the properties of PDLLA and nHA, two
      potential drug delivering and bone repair materials for spinal TB reconstruction.
      We also presented two alternatives for spinal TB in future. Two strategies have
      the potential for treating spinal TB in the future. One such strategy consists of
      mixing anti-TB drugs, PDLLA with nHA to fabricate a novel three-dimensional (3D)
      porous scaffold via 3D printing (3DP) technology. Another is preparing a novel
      titanium mesh implant coated with drugs/PDLLA/nHA composites by solvent
      evaporation and low-temperature drying technology. These two hypotheses have
      recently been tested in a laboratory setting by our team. 

PMID- 24328923
TI  - Dimensionality of self-compassion: translation and construct validation of the
      self-compassion scale in an Italian sample.
AB  - BACKGROUND: The construct of self-compassion is receiving increased attention due
      to its strong link to mental health. Nonetheless, many questions concerning its
      dimensionality and construct validity remain open. AIMS: The purpose of this
      study was to evaluate the factorial structure and construct validity of the Self
      Compassion Scale (SCS) in a sample of 424 Italian participants ranging in age
      from 17 to 65 years. METHOD: SCS was translated with a back-translation procedure
      and then administered through an on-line survey, along with measures of self
      blame, subjective loneliness, emotion regulation, depression and anxiety.
      RESULTS: Confirmatory factor analysis (CFA) confirmed the six-factor model both
      in the overall sample and in gender and age subgroups. CFA did not support the
      single higher-order factor of self-compassion, originally found by the author of
      the scale. Negative associations of Self-Kindness, Common Humanity and
      Mindfulness subscales with anxiety and depression were confirmed. Moreover,
      negative correlations of these subscales with self-blame, positive correlations
      with reappraisal and non-significant associations with expressive suppression and
      subjective loneliness were found, unveiling aspects of the construct not fully
      investigated in empirical research. CONCLUSIONS: Findings suggest that the SCS is
      a reliable tool but its dimensionality may vary according to different cultural
      contexts.

PMID- 24328924
TI  - Obstructive sleep apnea and heart rate variability in male patients with
      metabolic syndrome: cross-sectional study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is often accompanied by the metabolic
      syndrome. Because both conditions are associated with depressed heart rate
      variability (HRV) separately, our aim was to study whether co-morbid OSA is
      associated with more reduced HRV in male patients with the metabolic syndrome.
      METHODS: In this cross-sectional study, 35 men (age, 57+/-11 years) with the
      metabolic syndrome (according to International Diabetes Federation criteria) were
      included. OSA severity was defined by the apnea-hypopnea index (AHI). HRV was
      assessed by 24-hr ambulatory electrocardiographic monitoring. Standard deviation
      of all normal-to-normal RR intervals (SDNN), the high frequency power (HFP), and
      the ratio of low- to high-frequency power (LF/HF) were measured. RESULTS: There
      were 14, 6, and 8 cases of severe (AHI >=30/hr), moderate (15/hr<=AHI <30/hr),
      and mild (5/hr <=AHI <15/hr) OSA, respectively. Seven patients had no OSA.
      Patients with mild-moderate or severe OSA had reduced SDNN and HFP values
      compared to those without OSA. Increasing OSA severity was associated
      significantly with lower daytime LF/HF ratio [standardized beta regression
      coefficient (beta)=-0.362, P=0.043] and higher night/day LF/HF ratio (beta=0.377,
      P=0.023) after controlling for age, duration of diabetes, and severity of
      metabolic syndrome. CONCLUSIONS: Co-morbid OSA is associated with decreased
      overall HRV, parasympathetic loss, and impaired diurnal pattern of sympathovagal
      balance that may further increase the cardiovascular vulnerability of male
      patients with the metabolic syndrome. The role of the HRV analysis in the risk
      assessment of these patients warrants further studies.

PMID- 24328925
TI  - Partial aggregation of silver nanoparticles induced by capping and reducing
      agents competition.
AB  - It is well known that nanomaterials properties and applications are dependent on
      the size, shape, and morphology of these structures. Among nanomaterials, silver
      nanoparticles (AgNPs) have attracted attention since they have considerably
      versatile properties, such as a variable surface area to volume ratio, which is
      very useful for many biomedical and technological applications. Within this
      scenario, small nanoparticle aggregates can have their properties reduced due to
      the increased size and alterations in their shape/morphology. In this work,
      silver nanoparticles aggregation was studied through chemical reduction of silver
      nitrate in the presence of sodium borohydride (reducing agent) and sodium citrate
      (capping agent). By changing the amount of reducing agent along the reaction,
      unaggregated and partially aggregated samples were obtained and characterized by
      UV-vis, zeta potential, and SAXS techniques. pH was measured in every step of the
      reaction in order to correlate these results with those obtained from structural
      techniques. Addition of the reducing agent first causes the reduction of Ag(+) to
      silver nanoparticles. For higher concentrations of sodium borohydrate, the
      average AgNPs size is increased and NPs aggregation is observed. It was found
      that zeta potential and pH values have a strong influence on AgNPs formation,
      since reducing agent addition can induce partial removal of citrate weakly
      associated on the AgNPs surface and increase the ionic strength of the solution,
      promoting partial aggregation of the particles. This aggregation state was duly
      identified by coupling SAXS, zeta potential and pH measurements. In addition, the
      SAXS technique showed that aggregates formed along the process are elongated-like
      particles due to the exponential decay evidenced through SAXS curves. 

PMID- 24328927
TI  - Persisters and beyond: mechanisms of phenotypic drug resistance and drug
      tolerance in bacteria.
AB  - One of the challenges in clinical infectious diseases is the problem of chronic
      infections, which can require long durations of antibiotic treatment and often
      recur. An emerging explanation for the refractoriness of some infections to
      treatment is the existence of subpopulations of drug tolerant cells. While
      typically discussed as "persister" cells, it is becoming increasingly clear that
      there is significant heterogeneity in drug responses within a bacterial
      population and that multiple mechanisms underlie the emergence of drug tolerant
      and drug-resistant subpopulations. Many of these parallel mechanisms have been
      shown to affect drug susceptibility at the level of a whole population. Here we
      review mechanisms of phenotypic drug tolerance and resistance in bacteria with
      the goal of providing a framework for understanding the similarities and
      differences in these cells.

PMID- 24328926
TI  - Gating function of isoleucine-116 in TM-3 (position III:16/3.40) for the activity
      state of the CC-chemokine receptor 5 (CCR5).
AB  - BACKGROUND AND PURPOSE: A conserved amino acid within a protein family indicates
      a significance of the residue. In the centre of transmembrane helix (TM)-5,
      position V:13/5.47, an aromatic amino acid is conserved among class A 7TM
      receptors. However, in 37% of chemokine receptors - a subgroup of 7TM receptors -
      it is a leucine indicating an altered function. Here, we describe the
      significance of this position and its possible interaction with TM-3 for CCR5
      activity. EXPERIMENTAL APPROACH: The effects of [L203F]-CCR5 in TM-5 (position
      V:13/5.47), [I116A]-CCR5 in TM-3 (III:16/3.40) and [L203F;G286F]-CCR5
      (V:13/5.47;VII:09/7.42) were determined in G-protein- and beta-arrestin-coupled
      signalling. Computational modelling monitored changes in amino acid conformation.
      KEY RESULTS: [L203F]-CCR5 increased the basal level of G-protein coupling (20-70%
      of Emax ) and beta-arrestin recruitment (50% of Emax ) with a threefold increase
      in agonist potency. In silico, [I116A]-CCR5 switched chi1-angle in [L203F]-CCR5.
      Furthermore, [I116A]-CCR5 was constitutively active to a similar degree as
      [L203F]-CCR5. Tyr(244) in TM-6 (VI:09/6.44) moved towards TM-5 in silico,
      consistent with its previously shown function for CCR5 activation. On
      [L203F;G286F]-CCR5 the antagonist aplaviroc was converted to a superagonist.
      CONCLUSIONS AND IMPLICATIONS: The results imply that an aromatic amino acid in
      the centre of TM-5 controls the level of receptor activity. Furthermore, Ile(116)
      acts as a gate for the movement of Tyr(244) towards TM-5 in the active state, a
      mechanism proposed previously for the beta2 -adrenoceptor. The results provide an
      understanding of chemokine receptor function and thereby information for the
      development of biased and non-biased antagonists and inverse agonists.

PMID- 24328928
TI  - Generation of intra-oral-like images from cone beam computed tomography volumes
      for dental forensic image comparison.
AB  - Identification of unknown individuals using dental comparison is well established
      in the forensic setting. The identification technique can be time and resource
      consuming if many individuals need to be identified at once. Medical CT (MDCT)
      for dental profiling has had limited success, mostly due to artifact from metal
      containing dental restorations and implants. DESCRIPTION: The authors describe a
      CBCT reformatting technique that creates images, which closely approximate
      conventional dental images. METHOD: Using a i-CAT Platinum CBCT unit and standard
      issue i-CAT Vision software, a protocol is developed to reproducibly and reliably
      reformat CBCT volumes. The reformatted images are presented with conventional
      digital images from the same anatomic area for comparison. CONCLUSION: The
      authors conclude that images derived from CBCT volumes following this protocol
      are similar enough to conventional dental radiographs to allow for dental
      forensic comparison/identification and that CBCT offers a superior option over
      MDCT for this purpose.

PMID- 24328929
TI  - Welfare gains and losses caused by clinical practice guidelines.
AB  - Clinical practice guidelines (CPGs) for health professionals can have a variety
      of welfare implications. These may result from a reduction in practice variation
      in the form of overuse, underuse and misuse or a shift in resources between
      patient groups. The purpose of this article is to discuss welfare gains and
      losses caused by CPGs for health professionals. To this end, the article
      distinguishes between CPGs with and without the inclusion of economic evidence.
      Based on a framework, this article shows that CPGs, which include economic
      evidence, can actually lead to a welfare loss by misjudging the maximum cost
      effectiveness threshold or ignoring altruistic concerns for patients. Given that
      a significant portion of CPGs currently considers costs and cost-effectiveness of
      treatment, this practice may need to be reassessed in jurisdictions where a cost
      effectiveness threshold has not been appropriately defined and a public consensus
      on the trade-off between cost-effectiveness and equity does not yet exist. 

PMID- 24328930
TI  - Aquatic aerobic exercise for children with cerebral palsy: a pilot intervention
      study.
AB  - PURPOSE: The primary purpose of this pilot study was to evaluate the
      effectiveness of a14-week aquatic exercise program on gross motor function and
      walking endurance in children with cerebral palsy (CP). The secondary purpose was
      to evaluate changes in functional strength, aerobic capacity and balance. METHOD:
      A prospective time series group design consisting of four measurement sessions
      (two baseline, one post intervention, and 1-month follow-up) was used. Eight
      ambulatory children ages 6-15 years with CP and classified at Gross Motor
      Function Classification System Level I or Level III participated in an aquatic
      aerobic exercise program. RESULTS: Significant improvements were observed for the
      primary outcomes of gross motor function and walking endurance. No significant
      differences between any of the secondary measures were observed, although all of
      the measures demonstrated trends of improvement after intervention. CONCLUSION:
      Ambulatory children with CP may improve their gross motor skills and walking
      endurance after an aquatic exercise program held twice per week for 14 weeks,
      utilizing moderate-to-vigorous exercise intensity and consisting of functional
      activities.

PMID- 24328931
TI  - Assessment of subjective and motor fatigue in Polio survivors, attending a
      Postpolio clinic, comparison with healthy controls and an exploration of clinical
      correlates.
AB  - PURPOSE: Polio survivors experience declining mobility, pain and fatigue. The
      extent of motor fatigue and its impact on mobility and quality of life, in
      addition to other commonly reported impairments requires evaluation. METHODS: An
      observational, case-control, cross-sectional design was used to assess 30 Polio
      survivors and 30 age- and sex-matched controls. Muscle strength and motor fatigue
      were assessed using fixed dynamometry. Fatigue, pain and quality of life were
      assessed using the Piper Fatigue Scale, the Fatigue Severity Scale, visual
      analogue scales and the RAND Short Form-36, respectively. An 8-min walking test,
      including physiological cost index (PCI), evaluated mobility. RESULTS: A
      significant difference in motor fatigue was identified only in hand grip (p =
      0.03). Polio survivors were significantly weaker (p < 0.001) and more fatigued (p
      < 0.001) than controls. Motor fatigue was not related to subjective fatigue,
      mobility or quality of life. Muscle strength predicted mobility. Pain and fatigue
      were associated with lower mental quality of life, while PCI was associated with
      physical quality of life. CONCLUSION: Motor fatigue has been identified in Polio
      survivors but was only significantly different in hand grip, using this approach.
      Pain, fatigue and elevated energy cost of walking negatively influenced quality
      of life. Motor fatigue was unrelated to subjective fatigue, mobility or quality
      of life.

PMID- 24328932
TI  - Effects on centre-based training and home-based training on physical function,
      quality of life and fall incidence in community dwelling older adults.
AB  - This was a quasi-experimental study to compare the effects of center-based
      training with home-based training on physical function, quality of life and fall
      incidence in older adults. Fifty older adults were recruited to receive exercise
      training for 6 months. Participants in the center-based group received training
      under supervision of a physiotherapist at the day training center. Those in the
      home-based group received training assisted by a care worker at home. The outcome
      measures were the Elderly Mobility Scale (EMS), Berg Balance Scale (BBS), Numeric
      Pain Rating Scale (NPRS), Short-form 12 (SF-12) and fall incidence. Assessments
      were performed on all participants before and after the 6-month intervention
      period. Center-based training supervised by a physiotherapist was found to have
      beneficial effects on physical function, quality of life and fall incidence while
      home-based training assisted by a care worker had no effect on physical condition
      and self-rated health status in community dwelling older adults. Service agents
      should provide center-based or home-based training to the ageing population in a
      user-friendly way with consideration of factors such as rehabilitation potential
      and accessibility of transportation.

PMID- 24328935
TI  - Positive inductive effect of swine interleukin-4 on immune responses elicited by
      modified live porcine reproductive and respiratory syndrome virus (PRRSV)
      vaccine.
AB  - Porcine reproductive and respiratory syndrome (PRRS) has become one of the most
      economically important diseases to the global pork industry. Currently, the
      efficacies of available commercial vaccines remain questionable: the modified
      live-PRRSV vaccines (MLVs) were generally effective but variable in sufficient
      protection, and the outcomes of inactivated-PRRSV vaccines (IVs) in the field
      were not very promising. In the present study, we investigated the effect of
      swine interleukin 4 (IL-4) on the development of virus-specific immune responses
      elicited by an MLV. The antibody titer against PRRSV membrane proteins in pigs
      elicited by MLV plus recombinant plasmid encoding IL-4 (group 3) was
      significantly higher than those elicited by MLV alone (group 1) and MLV plus
      empty plasmid (group 2) from 35 days post-inoculation (dpi). Similarly, the
      neutralizing efficacy of sera from group 3 was markedly enhanced compared with
      group 1 and group 2. In cellular immunity, the ratio of CD3+CD4+/CD3+CD8+ T
      lymphocyte subpopulations from group 3 monitored by flow cytometry (FCM) was
      significantly higher than those from group 1 and group 2 from 42 dpi to 21 days
      post-challenge (dpc). After viral challenge, pigs in group 3 showed significantly
      lower virus loads in peripheral blood measured by a real-time quantitative PCR
      (RT-qPCR), as compared with those in group 1 and group 2. Pigs in group 1 and
      group 2 had a low fever and displayed mild inappetence, lethargy, rough hair
      coats, and no lung lesions, while those in group 3 showed almost no clinical
      signs, no lung lesions. The scores of clinical signs of pigs in group 3 were
      significantly lower than those in both group 1 and group 2. Interestingly, the
      scores of lung lesions showed no significant differences among the three groups.
      Our results indicate that swine IL-4 markedly enhanced the protective immune
      response of pigs and improved the efficacy of the MLV in preventing PRRS disease.

PMID- 24328934
TI  - Non-random lymphocyte distribution among virus-infected cells of the respiratory
      tract.
AB  - The rules of T cell positioning within virus-infected respiratory tract tissues
      are poorly understood. We therefore marked cervical lymph node or spleen cells
      from Sendai virus (SeV) primed mice and transferred lymphocytes to animals
      infected with SeV expressing an enhanced green fluorescent protein (SeV-eGFP).
      Confocal imaging showed that when T cells entered a field of infected respiratory
      tract epithelium, they assumed a spatial distribution that maximized distances
      between each donor cell and its nearest neighbor. We therefore hypothesized that
      lymphocytes repelled one another by altering their chemokine/cytokine
      microenvironment. Subsequent in vitro tests confirmed that when SeV-primed
      lymphocytes were co-cultured with infected respiratory tract stroma, there was a
      profound upregulation of chemokines including RANTES, CXCL9, CXCL10, and CCL2.
      Based on these data, we propose that newly resident lymphocytes within virus
      infected respiratory tract tissues may create halos of chemokines/cytokines to
      mark their territories; lymphocyte cross-talk may then inhibit cell overlap and
      redundancy to expedite virus clearance.

PMID- 24328936
TI  - Methods of quantifying microRNAs for hypoxia research: classic and next
      generation.
AB  - SIGNIFICANCE: Recent evidence is uncovering the ever-increasing importance of
      microribonucleic acids (miRNAs) in the hypoxia response. In order to investigate
      the important roles that these small RNAs play, methods of quantification whether
      using classic single-gene methods or genome-wide technologies are necessary to
      obtain a global picture of the differential expression of miRNAs in hypoxia and
      their interplay with protein coding genes. RECENT ADVANCES: Building on the
      groundwork of classic quantitative polymerase chain reaction (qPCR) and
      microarrays, the advent of next-generation sequencing technology has
      revolutionized how small RNAs can be detected and quantified on a genome-wide
      scale and without a priori knowledge of the small RNA sequence. This method
      delivers accurate and comprehensive data on the expression and sequence of all
      expressed small RNAs, and the data can be further combined with other sequencing
      modalities to better understand miRNAs via integrated genomic analyses. CRITICAL
      ISSUES: Advancing technology has increased the need for better methods of sample
      and library preparation and for bioinformatics tools. Speed, cost, sample input,
      and analysis expertise remain the mainstay critical issues of small RNA
      sequencing. FUTURE DIRECTIONS: Future hypoxia research will benefit from the
      application of genome-wide sequencing technologies. Analyses that combine
      genomic, transcriptomic, chromosome conformation, DNA/RNA-protein binding, and
      proteomics will help greatly advance hypoxia miRNA research.

PMID- 24328937
TI  - Are attendings different?. Intensivists explain their handoff ideals,
      perceptions, and practices.
AB  - PURPOSE: What is known about physician handoffs is almost entirely limited to
      resident practice, but attending physicians ultimately determine care plans and
      goals of care. This study sought to understand what is unique about attending
      intensivist handoffs, to identify perceptions of the ideal content and format of
      intensive care unit (ICU) attending handoffs, and to understand how ideal and
      reported practices are aligned in the delivery of care. METHODS: Intensivists in
      active practice in U.S. adult academic ICUs were purposively sampled and
      interviewed over 9 months in 2011 to 2012. MEASUREMENTS AND MAIN RESULTS: Thirty
      attendings from 15 institutions in nine U.S. states were interviewed. Subjects'
      specialties included anesthesiology, emergency medicine, internal medicine, and
      surgery. The "perfect handoff" was described as succinct, included verbal plus
      written communication, and took place in person. Respondents believed that the
      attending handoff should be less detailed than resident handoffs. Most attendings
      participated in handoffs at the end of each ICU rotation (n = 26). Standardized
      handoff practice was rare (n = 1). Media used for handoffs included combinations
      of telephone conversations (n = 25), in-person communications (n = 11), e-mail (n
      = 9), or text message (n = 2). Handoff duration varied from 10 to 120 minutes for
      5 to 42 patients. Five of 30 respondents had undergone formal training in how to
      conduct handoffs. CONCLUSIONS: A national sample of academic intensivists
      identified common ideal attributes of attending handoffs, yet their reported
      handoff practices varied widely. Ideal handoff practices may form the basis of
      future interventions to improve communication between intensivists.

PMID- 24328938
TI  - The correlation between the comprehensive nutrition index and quality of life of
      patients with nasopharyngeal carcinoma treated by intensity-modulated
      radiotherapy.
AB  - The purpose of this study was to compare the changing tendency of nutrition with
      54 nasopharyngeal carcinoma patients during intensity-modulated radiation therapy
      (IMRT), and to investigate the correlation between comprehensive nutritional
      status and quality of life (QoL), which was assessed by the European Organization
      for Research and Treatment of Cancer Core Quality-of-Life Questionnaire. The
      nutritional index, including body mass index, ideal body weight percentage, usual
      body weight percentage, albumin, hemoglobin, and total lymphocyte count (TLC),
      was evaluated at 2 time points: within 48 h after admission (T1) and at the end
      of treatment with IMRT (T2). A statistically significant downgrade of every index
      was observed during IMRT. A comprehensive nutritional model was established by
      principal components analysis at T2. QoL scores of functional (P = 0.002) and the
      global QoL scales (P = 0.001) existed a positive correlation with comprehensive
      nutritional status. QoL scores of symptom scales (P = 0.002) and 6 single items
      (P = 0.005) had a negative correlation with it. The scores of global QoL scales
      in comprehensive nutrition of normal (20.4%), moderate (55.6%), and severe
      malnutrition (24.1%) were 69.70 +/- 17.98, 48.33 +/- 19.25, and 37.18 +/- 24.67,
      respectively. Patients with different nutritional status had different QoL (B =
      10.405, SE = 2.828, t = 3.680, P = 0.001). Multiaspect nutritional supports
      should be enhanced to improve patients' comprehensive nutritional status during
      treatment. 

PMID- 24328939
TI  - Melanoma associated with tumour necrosis factor-alpha inhibitors: a Research on
      Adverse Drug events And Reports (RADAR) project.
AB  - BACKGROUND: Tumour necrosis factor-alpha inhibitors (TNFalphaIs) are used for
      treatment of inflammatory disorders. There is evidence linking these agents with
      occurrence of malignancies. For four out of five TNFalphaIs the Food and Drug
      Administration (FDA) label states, 'melanoma has been reported in patients
      treated with these agents'. OBJECTIVES: To determine whether a statistically
      significant association exists between administration of TNFalphaIs and
      development of malignant melanoma. METHODS: We searched the FDA Adverse Event
      Reporting System (FAERS) database for terms related to melanoma and TNFalphaIs
      for detection of safety signals. We also searched a large urban academic
      electronic medical record (EMR) database for which we calculated the relative
      risk (RR) of melanoma in subjects exposed to TNFalphaIs vs. nonexposed subjects.
      RESULTS: There were 972 reports of melanoma associated with a TNFalphaI
      identified in the FAERS database, with 69 reports among individuals using more
      than one TNFalphaI. A safety signal was detected for infliximab, golimumab,
      etanercept and adalimumab, but not certolizumab pegol. For TNFalphaIs as a class
      of drugs, a safety signal was detectable in the FAERS database, and RR was
      significant in the EMR database. For the EMR cohort, 6045 patients were exposed
      to TNFalphaIs and 35 cases of melanoma were detected. Significance for RR was
      detected for adalimumab (RR 1.8, P = 0.02) and etanercept (RR 2.35, P = 0.0004 <
      0.001). CONCLUSIONS: We identified a significant association between exposure to
      TNFalphaIs and malignant melanoma in two different analyses. Our findings add to
      existing evidence linking these agents with the occurrence of malignant melanoma.
      Additional investigations are required to explore this association further along
      with the risk of melanoma with TNFalphaI therapy.

PMID- 24328940
TI  - Perforated Meckel's diverticulum in a very preterm baby revealed at birth.
AB  - Perforated Meckel's diverticulum (MD) in a preterm baby is very rare. We report a
      case of a very preterm baby, born at 29-week gestation, with a birth weight of
      1400 g, admitted in the third hour of life to our intensive care unit (ICU) for
      respiratory distress syndrome with abdominal distention. An abdominal radiograph
      showed a pneumoperitoneum. Laparotomy revealed Meckel's perforation. The baby was
      discharged healthy at the age of 16 days. MD should be kept in mind as one cause
      of an acute abdomen in preterm neonates mimicking necrotizing enterocolitis. To
      our knowledge, our patient is the third reported case described in the literature
      and the first one revealed at birth. 

PMID- 24328941
TI  - Amelia-meromelia sequence with atrial septal defect-a rare occurrence.
AB  - Amelia and Meromelia may either present as an isolated defect or associated with
      other malformations; and the diagnosis is mainly clinical. The antenatal period
      of the case presented here was medically unsupervised but uneventful. The baby
      had bilateral upper limb Meromelia and bilateral lower limb Amelia along with a
      small ostium secundum atrial septal defect. Except for the young age of mother,
      there was no other obvious risk factor in this case. The baby had a normal and
      healthy neonatal outcome whereas most such cases are either stillborn or end in
      early neonatal death. 

PMID- 24328942
TI  - Spectroscopy and quantum mechanics of the hydrogen molecular cation: a test of
      molecular quantum mechanics.

PMID- 24328943
TI  - Response to letter: folate deficiency in Crohn's disease.
AB  - Folate deficiency in patients with Crohn's disease may be due to a combination of
      factors: poor diet, malabsorption, increased requirements due to inflammation of
      the mucosa, and the taking of certain drugs as sulfasalazine and methotrexate. A
      significant proportion of patients with Crohn's disease suffer from folate
      deficiency, suggesting that regular screening should be performed.

PMID- 24328944
TI  - Effects of familial climate on the adolescents' driving habits: a recent
      literature.
AB  - Driving is a functional task that requires a complex interaction of visual
      perception, cognitive and motor skills. Next to circulatory diseases and cancer,
      road accidents remain the third epidemic cause of death internationally, with
      approximately half a million teen drivers killed annually. Driver behaviour has
      been cited as the pervasive marker of automotive crashes. A reliable and firm
      relationship between the positive parental model, message, and communication has
      been established. Specifically, the familial climate is proposed to be an
      important element of reinforcement, modelling, support and environmental
      determinant in interpreting personal perceptions, habits, values, and belief
      system. Confirming the assertion, this bibliographic review presents the most
      recent research findings on the contributions of families to the driving habits
      of teens. The emphasis is speculated on parental alcohol use, aggressiveness,
      attention-deficit/hyperactivity disorder, relationship, and intergenerational
      transmission of driving styles. Besides, the effects of familial supervision,
      monitoring, education and awareness, and genders, partners, and demographic
      influence on the driving habits are discussed and outlined. 

PMID- 24328946
TI  - Dual-color electroluminescence from dot-in-bulk nanocrystals.
AB  - The emission color from colloidal semiconductor nanocrystals (NCs) is usually
      tuned through control of particle size, while multicolor emission is obtained by
      mixing NCs of different sizes within an emissive layer. Here, we demonstrate that
      recently introduced "dot-in-bulk" (DiB) nanocrystals can emit two-color light
      under both optical excitation and electrical injection. We show that the
      effective emission color can be controlled by adjusting the relative amplitudes
      of the core and shell emission bands via the intensity of optical excitation or
      applied bias in the cases of photoluminescence (PL) and electroluminescence (EL),
      respectively. To investigate the role of nonradiative carrier losses due to
      trapping at intragap states, we incorporate DiB NCs into functional light
      emitting diodes and study their PL as a function of applied bias below the EL
      excitation threshold. We show that voltage-dependent changes in core and shell
      emissions are not due to the applied electric field but rather arise from the
      transfer of charges between the anode and the NC intragap trap sites. The changes
      in the occupancy of trap states can be described in terms of the raising
      (lowering) of the Fermi level for reverse (direct) bias. We find that the applied
      voltage affects the overall PL intensity primarily via the electron-trapping
      channel while bias-induced changes in hole-trapping play a less significant role,
      limited to a weak effect on core emission. 

PMID- 24328947
TI  - Foreword. Management of acute rhinosinusitis and acute otitis media.

PMID- 24328948
TI  - Section one. Acute and chronic rhinosinusitis.
AB  - Rhinosinusitis is one of the most common conditions seen by family physicians.
      Most cases are viral in nature and resolve spontaneously. When symptoms persist
      for 10 days or more or are accompanied by severe pain and fever, bacterial
      sinusitis may be present. Current guidelines recommend that acute bacterial
      sinusitis be treated with amoxicillin-clavulanate. Chronic bacterial sinusitis
      typically involves a change in the sinus ostia and microbiology. This rarely
      resolves with antibiotic treatment alone and often warrants surgical
      intervention. Fungal sinusitis is a rare condition seen more often in
      immunosuppressed individuals and manifests in severe symptoms along with possible
      neurologic findings. 

PMID- 24328949
TI  - Section two: otitis media.
AB  - With the widespread use of vaccinations against Streptococcus pneumoniae, the
      frequency of acute otitis media (OM) has decreased significantly in recent years.
      Current management varies considerably in different countries, but there is
      consensus that most mild cases in children older than 6 months can be treated
      with observation and analgesics. When antibiotic therapy is indicated for
      children younger than 6 months or older children with severe or unrelenting
      symptoms, initial management with amoxicillin or amoxicillin-clavulanate is
      recommended. For children with recurrent OM or persistent serous OM, prophylactic
      antibiotic regimens appear to be effective. Insertion of tympanostomy tubes can
      be useful to prevent recurrences but confers little benefit on speech
      acquisition. Tonsillectomy and adenoidectomy yield minimal benefit for children
      with OM. 

PMID- 24328950
TI  - Section three: oral cancers.
AB  - Oral cancers are uncommon in the United States. Risk factors for oral cancer
      include tobacco use, alcohol consumption, and high-risk oral human papillomavirus
      infection. Precancerous lesions, such as leukoplakia, may lead to oral cancers,
      but the majority of precancerous lesions never undergo malignant transformation.
      Management and prognosis for oral cancers vary widely depending on the site of
      the cancer. Lip cancers typically are detected early and have the greatest
      likelihood for cure and long-term patient survival. Cancers of the pharynx and
      tonsil have poor survival rates even when diagnosed in early stages. The best
      approach to preventing oral cancers is to control risk factors. 

PMID- 24328951
TI  - Section four: laryngitis and dysphonia.
AB  - Acute laryngitis is most often caused by viral illnesses through direct
      inflammation of the vocal cords or from irritation due to postnasal drainage.
      Bacterial infections, such as acute epiglottitis, also can cause dysphonia but
      typically have other systemic symptoms as well as respiratory distress. Chronic
      laryngitis is characterized by symptoms lasting more than 3 weeks. Chronic vocal
      cord issues can be related to overuse or stress on the vocal cords resulting in
      nodules or polyps. Individuals in certain occupations, such as singers, school
      teachers, and chemical workers, are at greater risk of chronic laryngitis. The
      diagnostic approach to chronic laryngitis should include visualization of the
      vocal cords to rule out potential malignant lesions. For acute and chronic
      overuse symptoms, the best treatment is vocal rest. The use of antibiotics or
      decongestants should be discouraged. 

PMID- 24328952
TI  - Control of cell adhesion and detachment on Langmuir-Schaefer surface composed of
      dodecyl-terminated thermo-responsive polymers.
AB  - This study used Langmuir-Schaefer (LS) method to produce thermo-responsive poly(N
      isopropylacrylamide) (PIPAAm) modified surface. Dodecyl terminated-PIPAAm (PIPAAm
      C12) was synthesized by reversible addition-fragmentation chain transfer radical
      polymerization. PIPAAm-C12 was dropped on an air-water interface and formed
      Langmuir film by compressing. A surface pressure measurement revealed that PIPAAm
      C12 was floated and Langmuir films were formed on the interface. And the Langmuir
      film was transferred on a hydrophobic substrate to produce PIPAAm-C12 transferred
      surface (PIPAAm-LS surface). In the results of atomic force microscope,
      attenuated total reflection Fourier transform infrared spectroscope, and X-ray
      photoelectron spectroscope measurement, the transference of Langmuir films was
      demonstrated and densities could be precisely controlled. Ellipsometric
      measurements of PIPAAm-LS surfaces showed that the thicknesses of the surfaces
      were less than 10 nm. Cell adhesion and detachment were observed on the PIPAAm-LS
      surfaces. The amount of adhered cells on all LS surfaces was found to be similar
      on the control hydrophobic substrate at 37  degrees C. In regard to cell
      detachment, adhering cells rapidly detached themselves with higher densities and
      shorter PIPAAm-C12 molecules. In this method, the effect of densities and
      molecular weights on cell adhesion and detachment were observed. Our method
      should be proved novel insights for investigating cell adhesion and detachment on
      thermo-responsive surfaces. 

PMID- 24328953
TI  - Synthesis of nitrogen-containing furanose sugar nucleotides for use as enzymatic
      probes.
AB  - The sugar nucleotides UDP-2-acetamido-2-deoxy-alpha-D-galactofuranose (UDP
      GalfNAc) and UDP-2-azido-2-deoxy-alpha-D-galactofuranose (UDP-GalfN3) have been
      synthesized in preparative scale for the first time. These compounds are useful
      probes for studying the biosynthesis of glycans containing galactofuranose and/or
      2-acetamido-2-deoxy-alpha-D-galactofuranose residues.

PMID- 24328954
TI  - Plans and detours.
AB  - At various stages of my career, I made and followed plans for progress and
      growth. However, owing to several unexpected challenges, I had to make detours
      into unplanned vistas. When I look around at the careers of my former students
      and younger colleagues, I see fewer long-term, stable positions and frequent
      changes both in employers and in functions every ten or twenty years. Our
      curriculum prepares our students for manufacturing careers in the United States,
      but the current trend of corporate merger and outsourcing can suddenly turn their
      work into marketing or finance in the Far East. A fox that knows many tricks may
      be better suited to changing environments than a hedgehog that knows only one
      single trick. Perhaps future education should not only teach few subjects in
      depth for immediate career needs but also teach adaptability to unrelated
      challenges. 

PMID- 24328957
TI  - Crystallization-driven surface segregation and surface structures in poly(L
      lactide)-block-poly(ethylene glycol) copolymer thick films.
AB  - In this work, we used poly(L-lactide)-block-poly(ethylene glycol) (PLLA-b-PEG)
      copolymer thick films to investigate the effect of crystallization on surface
      segregation, surface crystal orientation, and morphology by attenuated total
      reflection Fourier transform infrared spectroscopy (ATR-FTIR), reflection optical
      microscopy (ROM), and two-dimensional grazing incident wide-angle X-ray
      scattering (2D GIWAXS) methods. ATR-FTIR results indicated that the surface
      fraction of PLLA block increased from 0.48 to 0.79 when T(c,PLLA) increased from
      70 to 110  degrees C. Polarized ATR-FTIR and 2D GIWAXS results indicated that
      PLLA crystal lamellae preferentially oriented parallel to the film surface with
      increasing T(c,PLLA). The surface crystallinity of PLLA was almost independent of
      T(c,PLLA), while the surface crystallinity of PEG decreased with increasing
      T(c,PLLA). On the basis of surface crystal orientation and crystallization
      kinetics, we suggested that the excess of PLLA component at the surface was
      mainly dominated by a coupling effect of crystallization behavior and surface
      segregation.

PMID- 24328955
TI  - Structural requirements of the human sodium-dependent bile acid transporter
      (hASBT): role of 3- and 7-OH moieties on binding and translocation of bile acids.
AB  - Bile acids (BAs) are the end products of cholesterol metabolism. One of the
      critical steps in their biosynthesis involves the isomerization of the 3beta
      hydroxyl (-OH) group on the cholestane ring to the common 3alpha-configuration on
      BAs. BAs are actively recaptured from the small intestine by the human Apical
      Sodium-dependent Bile Acid Transporter (hASBT) with high affinity and capacity.
      Previous studies have suggested that no particular hydroxyl group on BAs is
      critical for binding or transport by hASBT, even though 3beta-hydroxylated BAs
      were not examined. The aim of this study was to elucidate the role of the 3alpha
      OH group on BAs binding and translocation by hASBT. Ten 3beta-hydroxylated BAs
      (Iso-bile acids, iBAs) were synthesized, characterized, and subjected to hASBT
      inhibition and uptake studies. hASBT inhibition and uptake kinetics of iBAs were
      compared to that of native 3alpha-OH BAs. Glycine conjugates of native and
      isomeric BAs were subjected to molecular dynamics simulations to identify
      topological descriptors related to binding and translocation by hASBT. Iso-BAs
      bound to hASBT with lower affinity and exhibited reduced translocation than their
      respective 3alpha-epimers. Kinetic data suggests that, in contrast to native BAs
      where hASBT binding is the rate-limiting step, iBAs transport was rate-limited by
      translocation and not binding. Remarkably, 7-dehydroxylated iBAs were not hASBT
      substrates, highlighting the critical role of 7-OH group on BA translocation by
      hASBT, especially for iBAs. Conformational analysis of gly-iBAs and native BAs
      identified topological features for optimal binding as: concave steroidal
      nucleus, 3-OH "on-" or below-steroidal plane, 7-OH below-plane, and 12-OH moiety
      toward-plane. Our results emphasize the relevance of the 3alpha-OH group on BAs
      for proper hASBT binding and transport and revealed the critical role of 7-OH
      group on BA translocation, particularly in the absence of a 3alpha-OH group.
      Results have implications for BA prodrug design. 

PMID- 24328958
TI  - The danger of unintended consequences.

PMID- 24328959
TI  - Letter to the editor.

PMID- 24328962
TI  - Ten questions with .... : Kelvin Knight.

PMID- 24328963
TI  - Association roundtable: how can healthcare technology managemnt (HTM)
      professionals build bridges and alliances with other hospital departments.

PMID- 24328965
TI  - Ask George.

PMID- 24328966
TI  - Silent danger: opioids, PCA pumps, and the case for continuous monitoring.

PMID- 24328968
TI  - Adding value: how to become a high-performing HTM department.

PMID- 24328967
TI  - Worth the effort?: closed-loop infusion pump integration with the EMR.

PMID- 24328969
TI  - After a major merger, a hospital president faces the future.

PMID- 24328970
TI  - Daily briefing promotes hospital-wide transparency and patient safety.

PMID- 24328971
TI  - Medical device batteries: ubiquitous and problematic.

PMID- 24328972
TI  - Phacoemulsification systems.

PMID- 24328973
TI  - The promise of quantum computing.

PMID- 24328974
TI  - Preventive maintenance for warming units.

PMID- 24328976
TI  - Three indicators of an excellent HTM department.

PMID- 24328977
TI  - Software-related recalls: an analysis of records.
AB  - Public and internal databases were examined to evaluate software-related recalls
      in the medical device industry sector. In the analysis of recalls reported from
      2005 through 2011, 19.4% of medical device recalls are related to software. This
      paper includes analysis results, challenges faced in determining the causes, and
      examples and trends in software-related recalls. This information can be useful
      in enhancing our understanding of why medical devices fail, and it can help to
      improve medical device safety, and patient and public health. 

PMID- 24328979
TI  - The case for in-house laboratory equipment maintenance.

PMID- 24328978
TI  - Measuring the performance of maintenance service outsourcing.
AB  - The aims of this paper are (1) to identify the characteristics of maintenance
      service providers that directly impact maintenance service quality, using 18
      independent covariables; (2) to quantify the change in risk these covariables
      present to service quality, measured in terms of equipment turnaround time (TAT).
      A survey was applied to every maintenance service provider (n = 19) for
      characterization purposes. The equipment inventory was characterized, and the TAT
      variable recorded and monitored for every work order of each service provider (N
      = 1,025). Finally, the research team conducted a statistical analysis to
      accomplish the research objectives. The results of this study offer strong
      empirical evidence that the most influential variables affecting the quality of
      maintenance service performance are the following: type of maintenance,
      availability of spare parts in the country, user training, technological
      complexity of the equipment, distance between the company and the hospital, and
      the number of maintenance visits performed by the company. The strength of the
      results obtained by the Cox model built are supported by the measure of the
      Rp,e(2) = 0.57 with a value of Rp,e= 0.75. Thus, the model explained 57% of the
      variation in equipment TAT, with moderate high positive correlation between the
      dependent variable (TAT) and independent variables. 

PMID- 24328980
TI  - Effects of bacterial melanin on movement, posture, and skilled balancing deficits
      after unilateral destruction of substantia nigra pars compacta in rats.
AB  - Sixteen adult male rats were initially trained to an instrumental conditioned
      reflex (ICR) and subjected to unilateral destruction of substantia nigra pars
      compacta. Part of the animals was injected with bacterial melanin solution on the
      next day of destruction. The other 8 rats served as the control group. Recovery
      rates for ICR and dynamics of paralyzed hindlimb movements were studied in both
      groups. Conditioned reflex and contralateral to lesion hindlimb movements
      recovered faster in rats injected with bacterial melanin after the destruction.

PMID- 24328981
TI  - A single surgeon's experience with transanal endoscopic microsurgery over 20
      years with 153 early cancer cases.
AB  - BACKGROUND: The first author performed transanal endoscopic surgery (TEM) in 302
      patients in Japan for the last 20 years, 153 of which were early rectal cancer
      cases. The short- and long-term outcomes of the early rectal cancer cases are
      herein reported. MATERIAL AND METHODS: The original technique of TEM developed by
      Gerhard Buess was performed in all cases. The hospital records were reviewed to
      assess the clinical outcomes. A questionnaire was sent to the patients to analyze
      the long-term outcomes. RESULTS: One-hundred and fifty-three early cancer cases
      included 115 T0 and 38 T1 lesions. Full-thickness resection was performed in 36
      patients, while 117 underwent submucosal dissection. Conversion to laparoscopic
      low anterior resection occurred in one case. Mortality was nil. Major operative
      complication was noted in only one patient, who developed stenosis. Seven
      patients underwent immediate salvage surgery. Six patients died of recurrence of
      rectal cancer. Disease-free survival rate at year 5 was 93.7%. CONCLUSIONS: Our
      study, one of the largest series in the world, confirms that TEM is a preferable
      option in the surgical treatment of T0 and T1a rectal carcinoma. As long as early
      cancer cases are treated, submucosal resection seems to be sufficient. When risk
      of recurrence is found by pathological examination, immediate salvage operation
      is mandatory to improve the prognosis.

PMID- 24328982
TI  - The outburst age: how TEM ignited the MIS revolution.

PMID- 24328983
TI  - The director's cut - video editing as a training modality for minimally invasive
      surgery.

PMID- 24328984
TI  - Effects of realistic force feedback in a robotic assisted minimally invasive
      surgery system.
AB  - BACKGROUND: Robotic assisted minimally invasive surgery systems not only have the
      advantages of traditional laparoscopic procedures but also restore the surgeon's
      hand-eye coordination and improve the surgeon's precision by filtering hand
      tremors. Unfortunately, these benefits have come at the expense of the surgeon's
      ability to feel. Several research efforts have already attempted to restore this
      feature and study the effects of force feedback in robotic systems. The proposed
      methods and studies have some shortcomings. The main focus of this research is to
      overcome some of these limitations and to study the effects of force feedback in
      palpation in a more realistic fashion. MATERIAL AND METHODS: A parallel robot
      assisted minimally invasive surgery system (PRAMiSS) with force feedback
      capabilities was employed to study the effects of realistic force feedback in
      palpation of artificial tissue samples. PRAMiSS is capable of actually measuring
      the tip/tissue interaction forces directly from the surgery site. Four sets of
      experiments using only vision feedback, only force feedback, simultaneous force
      and vision feedback and direct manipulation were conducted to evaluate the role
      of sensory feedback from sideways tip/tissue interaction forces with a scale
      factor of 100% in characterising tissues of varying stiffness. Twenty human
      subjects were involved in the experiments for at least 1440 trials. Friedman and
      Wilcoxon signed-rank tests were employed to statistically analyse the
      experimental results. RESULTS: Providing realistic force feedback in robotic
      assisted surgery systems improves the quality of tissue characterization
      procedures. Force feedback capability also increases the certainty of
      characterizing soft tissues compared with direct palpation using the lateral
      sides of index fingers. CONCLUSION: The force feedback capability can improve the
      quality of palpation and characterization of soft tissues of varying stiffness by
      restoring sense of touch in robotic assisted minimally invasive surgery
      operations.

PMID- 24328985
TI  - Usefulness and safety of biliary percutaneous transluminal forceps biopsy (PTFB):
      our experience.
AB  - AIM: To evaluate the usefulness and safety of percutaneous transluminal forceps
      biopsy in patients suspected of having a malignant biliary obstruction. MATERIAL
      AND METHODS: Forty consecutive patients (21 men and 19 women; mean age, 71.9
      years) underwent forceps biopsy through percutaneous transhepatic biliary access
      performed to drain bile. Lesions involved the common bile duct (n 8), common
      hepatic duct (n 18), hilum (n 6), ampullary segment of the common bile duct (n 8)
      and were biopsied with 7-F biopsy forceps. Final diagnosis was confirmed with
      pathologic findings at surgery, or clinical and radiologic follow-up. RESULTS:
      Twenty-one of 40 biopsies resulted in correct diagnosis of malignancy. Thirteen
      biopsy diagnosis were proved to be true-negative. There were six false-negative
      and no false-positive diagnoses. Sensitivity, specificity and accuracy in
      aspecific biliary obstructions were 85%, 100% and 88,7% respectively. Sensitivity
      of biopsy in malignancies was higher than in benign obstructions (100% vs 68,4%,
      CI = 95%). Sensitivity was lower in the hilum tract and in the common bile duct
      than in other sites (CI = 95%). No major complications related to biopsy
      procedures occurred. CONCLUSIONS: Percutaneous transluminal forceps biopsy is a
      safe procedure, easy to perform through a transhepatic biliary drainage tract,
      providing high accuracy in the diagnosis of malignant biliary obstructions.

PMID- 24328986
TI  - Social movements in health.
AB  - Most public health practitioners know that public health has relied on biomedical
      advances and administrative improvements, but it is less commonly understood that
      social movements in health have also been sources of motivation for population
      health advances. This review considers the impacts of social movements focused on
      urban conditions and health, on the health of children, and on behavioral and
      substance-related determinants of health and illustrates how these movements have
      significantly influenced public health activities and programs. We hope this
      review will motivate public health workers to make common cause with social
      activists and to encourage social activists to ally with public health
      professionals. 

PMID- 24328987
TI  - Commentary: Generating rigorous evidence for public health: the need for new
      thinking to improve research and practice.
AB  - This commentary describes the concept of evidence-based public health, including
      the limitations of evidence. Increased attention to evidence may have numerous
      benefits for public health practice, including access to higher-quality
      information on what works, a higher likelihood of successful programs and
      policies being implemented, greater workforce productivity, and more efficient
      use of resources. To broaden thinking on the sources and scope of evidence, the
      three reviews in this symposium seek to (a) compare and contrast several
      evaluation designs that are alternatives to the randomized controlled trial; (b)
      describe two research approaches that are useful in addressing complex,
      multilevel public health issues (i.e., mixed methods research and mixed studies
      reviews); and (c) provide an overview of the value and approaches for generating
      practice-based evidence. These reviews highlight the complexity and
      interrelatedness of public health challenges, limitations of researcher-driven,
      quantitative approaches, and the need to broaden our current concepts of
      evidence. 

PMID- 24328988
TI  - Personal belief exemptions from school vaccination requirements.
AB  - Despite the impact vaccination has had on the control and prevention of many
      infectious diseases, some parents choose not to vaccinate their children.
      Although there is no federal law requiring vaccination of children in the United
      States, all states require evidence of vaccination against at least some diseases
      as a condition of school entry. Which vaccines are required; how many doses are
      required; whether entry requirements apply to child care, kindergarten, or middle
      school; and whether exemptions from vaccine requirements will be allowed all
      differ by state. All but two states allow some kind of personal belief exemption
      from school vaccination requirements. This article reviews the history of school
      vaccination requirements and exemptions, the legal status of state vaccination
      laws and exemptions, the impact of school vaccination requirements and personal
      belief exemptions on vaccination rates and disease incidence, and strategies for
      maintaining adequate vaccination rates in states that allow personal belief
      exemptions. 

PMID- 24328989
TI  - Public health and media advocacy.
AB  - Media advocacy blends communications, science, politics, and advocacy to advance
      public health goals. In this article, we explain how media advocacy supports the
      social justice grounding of public health while addressing public health's
      "wicked problems" in the context of American politics. We outline media
      advocacy's theoretical foundations in agenda setting and framing and describe its
      practical application, from the layers of strategy to storytelling, which can
      illuminate public health solutions for journalists, policy makers, and the
      general public. Finally, we describe the challenges in evaluating media advocacy
      campaigns. 

PMID- 24328990
TI  - Common food additive carrageenan stimulates Wnt/ beta-catenin signaling in
      colonic epithelium by inhibition of nucleoredoxin reduction.
AB  - Exposure to the common food additive carrageenan was previously associated with
      increased Wnt9A expression and increased cytoplasmic beta-catenin in human
      colonic epithelial cells. In this report, exposure of human colonic epithelial
      cells in culture and of mouse colonic epithelium in vivo to low concentrations of
      carrageenan is shown to activate the Wnt/beta-catenin signaling pathway, leading
      to increases in nuclear beta-catenin, T-cell factor/lymphoid enhancer factor
      activation, and cyclin D1 expression and decline in bone morphogenetic protein-4.
      These effects are mediated through carrageenan-induced reactive oxygen species
      (ROS), and inhibited by the ROS scavenger Tempol. Carrageenan exposure and ROS
      production inhibited thioredoxin reductase activity and increased oxidation of
      nucleoredoxin, a member of the thioredoxin family of redox proteins. When
      oxidized, nucleoredoxin co-immunoprecipitation with dishevelled (DVL) declined,
      enabling DVL to interact with and inhibit the cytoplasmic beta-catenin
      destruction complex, and facilitating nuclear translocation of beta-catenin. Both
      nucleoredoxin silencing and carrageenan exposure produced similar declines in
      thioredoxin reductase activity. In addition to activation of Wnt signaling,
      carrageenan exposure also increased Wnt9A mRNA expression in the mouse colonic
      epithelium and the human colonic epithelial cells, thereby potentially permitting
      ongoing stimulation of the Wnt/beta-catenin pathway. These findings suggest how a
      common dietary ingredient can contribute to colon carcinogenesis by effects on
      Wnt signaling and Wnt expression. 

PMID- 24328992
TI  - Preventing hyperthermia: a cross-over study comparing two negative pressure
      devices during continuous passive heat stress.
AB  - Heat-related illness and mortality increase significantly during heatwaves. Out
      of-hospital treatment to avoid elevation of body core temperature (hyperthermia)
      could be beneficial for selected patients. Negative pressure devices have been
      proposed as an effective treatment method. This study compared the effects of two
      devices on healthy volunteers under continuous passive heat stress in a climatic
      chamber. Nine subjects were studied in a prospective cross-over study on two
      separate days. Subjects were randomized to treatment with either CoreControl(r)
      (CC) or ThermoTube (TT) on the first day. They were exposed to an ambient
      temperature above skin temperature and high air humidity throughout the
      experiment. Treatment intended to prevent the development of hyperthermia started
      after 60 min of passive warming. Core temperature continued to rise during
      treatment with CC, whereas it dropped slightly and then stabilized during
      treatment with TT.

PMID- 24328991
TI  - Investigation of connexin 43 uncoupling and prolongation of the cardiac QRS
      complex in preclinical and marketed drugs.
AB  - BACKGROUND AND PURPOSE: Prolongation of the cardiac QRS complex is linked to
      increased mortality and may result from drug-induced inhibition of cardiac sodium
      channels (hNaV 1.5). There has been no systematic evaluation of preclinical and
      marketed drugs for their additional potential to cause QRS prolongation via gap
      junction uncoupling. EXPERIMENTAL APPROACH: Using the human cardiac gap junction
      connexin 43 (hCx43), a dye transfer 'parachute' assay to determine IC50 values
      for compound ranking was validated with compounds known to uncouple gap
      junctions. Uncoupling activity (and hNaV 1.5 inhibition by automated patch clamp)
      was determined in a set of marketed drugs and preclinical candidate drugs, each
      with information regarding propensity to prolong QRS. KEY RESULTS: The potency of
      known gap junction uncouplers to uncouple hCx43 was ranked (according to IC50 )
      as phorbol ester>digoxin>meclofenamic acid>carbenoxolone>heptanol. Among the
      drugs associated with QRS prolongation, 29% were found to uncouple hCx43 (IC50 <
      50 MUM), whereas no uncoupling activity was observed in drugs not associated with
      QRS prolongation. In preclinical candidate drugs, hCx43 and hNaV 1.5 IC50 values
      were similar (within threefold). No consistent margin over preclinical Cmax
      (free) was apparent for QRS prolongation associated with Cx43 inhibition.
      However, instances were found of QRS prolonging compounds that uncoupled hCx43
      with significantly less activity at hNaV 1.5. CONCLUSION AND IMPLICATIONS: These
      results demonstrate that off-target uncoupling activity is apparent in drug and
      drug-like molecules. Although the full ramifications of Cx inhibition remain to
      be established, screening for hCx43 off-target activity could reduce the
      likelihood of developing candidate drugs with a risk of causing QRS prolongation.

PMID- 24328993
TI  - Biphasic intra-thoracic pressure regulation augments cardiac index during porcine
      peritonitis: a feasibility study.
AB  - Preservation of cardiac output (CO) and pulmonary artery pressure (PAP) is vital
      to maintaining tissue oxygenation in sepsis. This feasibility study tested the
      hypothesis that therapeutic intra-thoracic pressure regulation (tIPR), delivered
      with a novel device, was designed to non-invasively enhance venous return by
      creating sub-atmospheric intra-thoracic pressure during the expiratory phase of
      mechanical ventilation, improves CO without fluid resuscitation in a porcine E.
      coli peritonitis model of sepsis. Seven pigs were intubated, anaesthetized and
      instrumented with a Swan-Ganz and femoral artery catheter. After a 30 min basal
      period, a fibrin clot containing 4-5 * 10(9) cfu kg(-1) E. coli O111.B4 was
      implanted in the peritoneum. One hour after clot implantation, tIPR was utilized
      for 30 min and then removed from the ventilator circuit for 30 min. This tIPR
      cycle was repeated 4-times. Changes in haemodynamic parameters were calculated by
      comparing pre-tIPR values to peak values during tIPR administration. Following
      peritonitis, tIPR significantly increased the peak cardiac index (mean +/- SEM)
      (14.8 +/- 2.6 vs 7.9 +/- 2.3 ml kg(-1)) and mean arterial pressure (10.2 +/- 1.5
      vs 4.9 +/- 1.1 mmHg) and simultaneously decreased PAP (-7.7 +/- 1.5 vs -2.7 +/-
      0.8 mmHg). These results support the feasibility of the concept that therapeutic
      application of negative expiratory pressure may provide a non-invasive and
      complementary approach to increase cardiac output and organ perfusion in the
      setting of septic shock.

PMID- 24328994
TI  - Are wash outs needed in clinical trials of topical agents?

PMID- 24328996
TI  - Postexcisional melanocytic regrowth extending beyond the initial scar: a novel
      clinical sign of melanoma.
AB  - BACKGROUND: Recurrent naevi are widely recognized to occur commonly following
      incomplete removal of melanocytic lesions. These lesions have been generally
      understood as representing benign imitators of melanoma. OBJECTIVES: To provide a
      formal description of the clinical findings of postexcisional melanocytic
      regrowth. METHODS: We examined all cases of recurrent pigmentation adjacent to
      scars from previous excisional biopsies of melanocytic naevi treated at a private
      dermatology practice from 1995 to 2012. RESULTS: We report nine cases of
      recurrence of melanocytic lesions that were melanomas. The most suspicious
      clinical feature for melanoma in these cases was the growth of the lesion beyond
      the confines of the initial scar, into the surrounding normal skin. CONCLUSIONS:
      This pattern of recurrence of a melanocytic lesion represents a little recognized
      and distinctive clinical presenting sign of melanoma.

PMID- 24328997
TI  - Effects of low-dose and high-dose postoperative radioiodine therapy on the
      clinical outcome in patients with small differentiated thyroid cancer having
      microscopic extrathyroidal extension.
AB  - BACKGROUND: It is unclear whether differentiated thyroid cancer (DTC) patients
      classified as intermediate risk based on the presence of microscopic
      extrathyroidal extension (ETE) should be treated with low or high doses of
      radioiodine (RAI) after surgery. We evaluated success rates and long-term
      clinical outcomes of patients with DTC of small tumor size, microscopic ETE, and
      no cervical lymph node (LN) metastasis treated either with a low (1.1 GBq) or
      high RAI dose (5.5 GBq). METHODS: This is a retrospective analysis of a
      historical cohort from 2000 to 2010 in a tertiary referral hospital. A total of
      176 patients with small (<=2 cm) DTC, microscopic ETE, and no cervical LN
      metastasis were included. Ninety-six patients were treated with 1.1 GBq (LO
      group) and 80 patients with 5.5 GBq (HI group). Successful RAI therapy was
      defined as (i) negative stimulated thyroglobulin (Tg) in the absence of Tg
      antibodies, and (ii) absence of remnant thyroid tissue and of abnormal cervical
      LNs on ultrasonography. Clinical recurrence was defined as the reappearance of
      disease after ablation, which was confirmed by cytologically or pathologically
      proven malignant tissue or of distant metastatic lesions. RESULTS: There was no
      significant difference in the rate of successful RAI therapy between the LO and
      HI groups (p=0.75). In a subgroup analysis based on tumor size, success rates
      were not different between the LO group (34/35, 97%) and the HI group (50/56,
      89%) in patients with a tumor size of 1-2 cm (p=0.24). In patients with smaller
      tumor size (<=1 cm), there was no significant difference in success rates between
      the LO (59/61, 97%) and HI groups (22/24, 92%; p=0.30). No patient had clinical
      recurrences in either group during the median 7.2 years of follow-up.
      CONCLUSIONS: Low-dose RAI therapy is sufficient to treat DTC patients classified
      as intermediate risk just by the presence of microscopic ETE.

PMID- 24328998
TI  - Waterhouse Friderichsen syndrome complicating fulminant Enterobacter cloacae
      sepsis in a preterm infant: the unresolved issue of corticosteroids.
AB  - Bilateral adrenal hemorrhage can complicate severe sepsis in the neonate and is
      most commonly attributed to meningococcal disease; however, it can be caused by
      other etiologic agents as well. We report herein a fatal case of Enterobacter
      cloacae sepsis in a preterm infant, resulting in massive adrenal hemorrhages.
      This is the first documented case of adrenal hemorrhage following infection with
      this pathogen. 

PMID- 24328999
TI  - Expression of FoxP3 protein plays a key role in thyroid tumors in children.
AB  - The expression of FoxP3 in tumor cells might play an important role in cancer
      progression. We evaluated the immunoexpression of FoxP3 in thyroid tumors in
      children. Studies revealed high nuclear FoxP3 expression in follicular adenoma,
      papillary carcinoma, follicular carcinoma and low in goiter. Malignant tumors and
      adenomas, revealed a statistically significant higher expression of FoxP3
      compared with the thyroid goiter. High FoxP3 expression in malignant lesions
      compared with low expression in goiter, may be indirect evidence of its role in
      carcinogenesis. Revealed high expression of FoxP3 in benign tumor, may suggest a
      strong activation of oncogenic processes in this lesion. 

PMID- 24329001
TI  - Antitumor activity of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective
      inhibitor, is highly dependent on its primary structure and steric configuration.
AB  - We recently reported the identification and characterization of a novel small
      chemical molecule designated FL118. FL118 selectively inhibits multiple cancer
      survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1,
      XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal
      models (Ling et al., PLoS One 2012, 7, e45571). Here, we report a follow-up study
      on the structure-activity relationship (SAR) of the hydroxyl group in the lactone
      ring of FL118. We found that the superior antitumor efficacy of FL118 heavily
      depends on its steric configuration through comparing the antitumor activity of
      FL118 with FL113 (the racemic mixture of FL118). Consistently, FL118 proved much
      more effective in inhibiting the expression of survivin, Mcl-1, and cIAP2, both
      in vitro and in vivo, compared to FL113. Additionally, Tet-on controlled
      induction of survivin or forced expression of Mcl-1 protects cancer cells from
      FL118-mediated growth inhibition and cell death. To further explore the SAR, we
      synthesized seven position 20-esterifiable FL118 and FL113 derivatives. Studies
      on these seven new compounds revealed that keeping a free hydroxyl group of FL118
      is also important for high antitumor efficacy. Together, these studies confirm
      the superior anticancer activity of FL118 and narrow the window for further SAR
      studies to generate novel analogues based on FL118 core structure on its other
      potential chemical positions. 

PMID- 24329002
TI  - Determining the cost-effectiveness of adult pneumococcal vaccination strategies.
AB  - The 23-valent pneumococcal polysaccharide vaccine is known to be economically
      reasonable in adults. With the 13-valent pneumococcal conjugate vaccine (PCV13)
      now available, the question is whether 23-valent pneumococcal polysaccharide
      vaccine offers sufficient protection in adults compared with PCV13. Our cost
      effectiveness analyses favor adult PCV13 use, but results depend largely on
      assumptions regarding PCV13 effectiveness in preventing non-bacteremic
      pneumococcal pneumonia and on herd immunity effects from childhood PCV13 use,
      neither of which are well characterized at present. An ongoing randomized trial
      of adult PCV13 use and future surveillance data should clarify these issues for
      some population groups, but in others, such as the immunocompromised, modeling
      that rigorously accounts for uncertainty can and should be used to assist
      policymakers in their decisions. 

PMID- 24329004
TI  - Effective hamiltonian theory and molecular dynamics.

PMID- 24329003
TI  - Wafer-scale synthesis of monodisperse synthetic magnetic multilayer nanorods.
AB  - A double exposure technique has been used to fabricate nanoimprint stamps for
      making monodisperse nanorods with controllable lengths. The nanorod length is
      defined by a normal photolithography projection process whereas the nanorod width
      is defined by an edge-lithography process using a soft polydimethylsiloxane
      (PDMS) contact mask. Taking advantage of edge-lithography, the nanorod width can
      be less than the diffraction limit of the exposure light. Using these nanorod
      stamps, synthetic magnetic multilayer (SMM) nanorods have been fabricated using
      nanoimprint lithography, resulting in a length variation of ~3%. Nanorod magnetic
      properties have been characterized in both longitudinal and in-plane transverse
      directions of the nanorods. A theoretical model has been established to explain
      the magnetic responses and has revealed that both shape anisotropy and interlayer
      interactions are important in determining the properties of SMM nanorods. 

PMID- 24329000
TI  - Imaging tumor hypoxia to advance radiation oncology.
AB  - SIGNIFICANCE: Most solid tumors contain regions of low oxygenation or hypoxia.
      Tumor hypoxia has been associated with a poor clinical outcome and plays a
      critical role in tumor radioresistance. RECENT ADVANCES: Two main types of
      hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic
      hypoxia results from the limited diffusion distance of oxygen, and cycling
      hypoxia primarily results from the variation in microvessel red blood cell flux
      and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor
      progression or regressive effects depending on the tumor model. However, there is
      a general trend toward the development of a more aggressive phenotype after
      cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal
      characteristics of tumor hypoxia and the changes to the tumor microenvironment
      can be analyzed. CRITICAL ISSUES: In this review, we focus on the biological and
      clinical consequences of chronic and cycling hypoxia on radiation treatment. We
      also discuss the advanced non-invasive imaging techniques that have been
      developed to detect and monitor tumor hypoxia in preclinical and clinical
      studies. FUTURE DIRECTIONS: A better understanding of the mechanisms of tumor
      hypoxia with non-invasive imaging will provide a basis for improved radiation
      therapeutic practices.

PMID- 24329005
TI  - Evaluation of a headspace solid-phase microextraction method for the analysis of
      ignitable liquids in fire debris.
AB  - The chemical analysis of fire debris represents a crucial part in fire
      investigations to determine the cause of a fire. A headspace solid-phase
      microextraction (HS-SPME) procedure for the detection of ignitable liquids in
      fire debris using a fiber coated with a mixture of three different sorbent
      materials (Divinylbenzene/Carboxen/Polydimethylsiloxane, DVB/CAR/PDMS) is
      described. Gasoline and diesel fuel were spiked upon a preburnt matrix (wood
      charcoal), extracted and concentrated with HS-SPME and then analyzed with gas
      chromatography/mass spectrometry (GC/MS). The experimental conditions--extraction
      temperature, incubation and exposure time--were optimized. To assess the
      applicability of the method, fire debris samples were prepared in the smoke
      density chamber (SDC) and a controlled-atmosphere cone calorimeter. The developed
      methods were successfully applied to burnt particleboard and carpet samples. The
      results demonstrate that the procedure that has been developed here is suitable
      for detecting these ignitable liquids in highly burnt debris.

PMID- 24329006
TI  - Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of
      histological gastritis, mucosal bacterial density, and levels of serum
      biomarkers.
AB  - OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin
      G (IgG) titer were unclear. This study investigated the associations of serum
      anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial
      density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II
      ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a
      screening program in northern China. Serum anti-H. pylori IgG measurements were
      available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG
      titer and serum biomarkers were measured using ELISA, and gastric biopsies were
      evaluated using standardized criteria. RESULTS. In patients with mild, moderate
      or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were
      17.3, 33.4 and 54.4 EIU (p for trend < 0.0001), respectively. As mucosal H.
      pylori density score increased from 0 to 3, the mean serum anti-H. pylori IgG
      titers also increased from 24.7 to 44.8 EIU (p for trend < 0.0001). Serum anti-H.
      pylori IgG titer was associated positively with serum PGI, PGII and gastrin-17
      concentrations and negatively with PGI/II ratio, and the association was the
      strongest for PGII. The mean PGII concentration of the patients in the highest
      quartile of IgG titer was twice the mean concentration of the patients in the
      lowest quartile (17.2 vs. 8.6 EIU, p < 0.0001). CONCLUSIONS. Our results suggest
      that serum anti-H. pylori IgG titer was associated positively with grade of
      histological gastritis, mucosal bacterial density and concentrations of serum
      PGI, PGII and gastrin-17, and negatively with PGI/II ratio.

PMID- 24329007
TI  - The effects of molecular structure on sol-to-gel transition of biodegradable
      poly(depsipeptide-co-lactide)-g-PEG copolymers.
AB  - We report on the effects of number and length of PEG chains in poly(depsipeptide
      co-dl-lactide)-g-poly(ethylene glycol) (P(DG-dl-LA)-g-PEG) copolymers on their
      sol-to-gel transition behavior. The graft-type copolymer is suitable for the
      systematic study of the effects of molecular structure and
      hydrophilic/hydrophobic balance on its sol-to-gel transition. We prepared various
      P(DG-dl-LA)-g-PEG copolymers through coupling reactions between the pendant
      carboxylic acid groups of P(GD-dl-LA) and the end hydroxyl group of MeO-PEG
      having various molecular weights. Temperature-responsive sol-to-gel transition of
      the obtained copolymer solution in phosphate-buffered solution (pH 7.4, ionic
      strength = 0.14) was investigated by the test tube inverting method and
      rheological measurements. P(GD-dl-LA)-g-PEG copolymer prepared from higher
      molecular weight PEG showed higher sol-to-gel transition temperatures compared
      with the copolymers prepared from lower molecular weight PEG, although these
      copolymers have similar weight content of PEG (23-24 wt.%). Similar trends were
      observed for groups of copolymers whose PEG contents were 27 or 30 wt.%. These
      results are informative for providing strategies on rational design of thermo
      gelling polymers. 

PMID- 24329008
TI  - Chemoenzymatic total synthesis and reassignment of the absolute configuration of
      ribisin C.
AB  - The enantiomerically pure and enzymatically derived cis-1,2-dihydrocatechol 5 has
      been converted, by two related pathways, into compounds 3 and ent-3. As a result,
      it has been determined that the true structure of the natural product ribisin C
      is represented by ent-3. 

PMID- 24329009
TI  - Whole blood and serum concentrations of metals in a Swedish population-based
      sample.
AB  - OBJECTIVE: While the potential toxicity of metals in humans is a well-established
      field of research, there are few studies that examine circulating concentrations
      of metals in large population-based samples. The aim of this study was to analyze
      levels of heavy metals and trace elements in both whole blood and serum in an
      elderly population, and to examine if gender, kidney function, haemoglobin or
      serum albumin could impact the distribution of metals between whole blood and
      serum. METHODS: Whole blood and serum samples from 1016 70-year-olds living in
      Uppsala, Sweden, were analyzed for aluminium, cadmium, cobalt, copper, chromium,
      mercury, manganese, molybdenum, nickel, lead, and zinc using inductively coupled
      plasma-sector field mass spectrometry (ICP-SFMS). Distribution between whole
      blood and serum was evaluated by the ratio between whole blood and serum
      concentration (B/S-ratio). RESULTS: Concentrations differed significantly between
      whole blood and serum measurements for all 11 metals (p < 0.00001). The highest
      B/S-ratios were found for lead (27), zinc (9), manganese (6), and nickel (4).
      Copper (0.86), cobalt (0.84), and molybdenum (0.86) showed B/S-ratios < 1.
      Especially the B/S-ratios for chromium, mercury and nickel correlated with kidney
      function (GFR) (r = 0.21, - 0.21 and - 0.36 respectively, p < 0.0001).
      CONCLUSIONS: The distribution between whole blood and serum varied considerably
      for different metals. This distribution correlated with physiological factors,
      mainly with kidney function, for several of the metals.

PMID- 24329012
TI  - Medial temporal lobe activation during autobiographical context memory retrieval
      of time and place and its dependency upon recency.
AB  - The contribution of the medial temporal lobe (MTL) to the retrieval of
      autobiographical memories is widely accepted. Results of former patient studies
      and functional imaging studies suggest different involvement of the MTL during
      the retrieval of autobiographical context information and the remoteness of
      these. Varying recency, the MTL contribution during chronological and locational
      autobiographical context information processing was investigated in this study.
      Thirteen males (mean = 25 years) judged the event's place or time in a two-choice
      recognition task. Subjects made significantly more errors on chronological
      judgments. Retrieval of chronological information activated the left MTL, while
      retrieval of locational information activated the MTL bilaterally. Retrieval of
      more recent than remote context information activated especially the right MTL.
      Our results underline different MTL contributions on the retrieval of
      autobiographical context information, depending on the content and on the
      remoteness of the event that took place. 

PMID- 24329013
TI  - Transanal endoscopic microsurgery: also for the treatment of retrorectal tumors.
AB  - Retrorectal tumors are an uncommon pathological entity. Their clinical importance
      arises from their occasional malignant nature or malignant transformation. The
      treatment of choice for most presacral tumors is surgical excision. The approach
      depends upon the upper limit of the lesion and the presumptive pathology. We
      reviewed the main features of these tumors with emphasis on transanal endoscopic
      microsurgery (TEM) as a viable surgical approach for the treatment of the
      lesions, undertaken in our institution. We present our small case series,
      consisting of six patients with retrorectal lesions who underwent local excision
      via TEM. Early and late postoperative outcomes are presented. TEM for retrorectal
      lesions appears to be a feasible and safe approach. A remarkably low morbidity
      favors TEM in selected patients.

PMID- 24329011
TI  - Novel method for proliferation of oral keratinocyte stem cells.
AB  - BACKGROUND AND OBJECTIVE: Stem cell-based tissue engineering offers clear
      advantages over conventional normal cell approaches. Owing to their specific
      characteristics, oral keratinocyte stem cells represent an attractive solution
      for therapeutic applications. However, when cultured in vitro, these cells lose
      their unique properties, acquiring a limited capacity for self-renewal, and
      differentiate rapidly into normal functional keratinocytes. The main aim of the
      present study was to develop an in-vitro method for the expansion of oral
      keratinocyte stem cells using a biomaterial approach. MATERIAL AND METHODS: Oral
      keratinocyte stem cells were isolated based on the identification of two surface
      markers - integrin alpha6beta4 and CD71 - using a magnetic method. The cells were
      cultured on specific substrates formed from blends of polymers: poly(lactide-co
      glycolide) (PLGA); poly(lactide-co-glycolide) + polyurethane (PLGA + PU); and
      poly(lactide-co-glycolide) + extracellular matrix (PLGA + ECM). The polymers were
      deposited using a laser-based technique - matrix-assisted pulsed laser
      evaporation. The cells were analyzed for cell size, cell proliferation, colony
      forming efficiency, cell adhesion markers (such as E-cadherin and beta 1
      integrin), keratinocyte stem cells and differentiation markers. The methods
      included ELISAs, immunofluorescence and atomic force microscopy imaging. RESULTS:
      After 14 d in culture, cells seeded on PLGA + PU stained positive for p63, cd44H,
      cytokeratin 19 and integrin alpha6beta4 and negative for involucrin, cytokeratin
      14 and cytokeratin 10. The levels of adhesion molecules were significantly
      increased in cells grown on PLGA + PU: at 14 d the E-cadherin levels were 5.4 +/-
      0.2 ng/mL (for cells grown on PLGA + PU) vs. 4.1 +/- 0.4 ng/mL (for cells grown
      on control medium) (n = 5, p < 0.05 Bonferroni). Oral keratinocyte stem cells
      grown on PLGA + PU had the highest colony-forming efficiency and proliferation
      rate, together with the smallest cell size, compared with cells grown on control
      medium or other polymeric substrates. CONCLUSION: The present study demonstrates
      that by culturing oral keratinocyte stem cells on PLGA blended with PU it is
      possible to preserve their phenotype in vitro and to guide their short-term
      expansion and proliferation. Certain stem-cell characteristics are preserved and
      their short-term expansion may be enhanced.

PMID- 24329014
TI  - Hybrid approach of retractor-based and conventional laparoscopy enabling
      minimally invasive hysterectomy in a morbidly obese patient: case report and
      review of the literature.
AB  - Minimally invasive hysterectomy in obese patients may be limited by laparoscopic
      sight on the one hand and by intraoperative complications related to reduced
      ventilation due to pneumoperitoneum on the other. Retractor-based laparoscopy
      offers an operative technique reducing anesthesia risks. We report the case of
      laparoscopic hysterectomy in an obese patient of short stature. Laparoscopic
      supracervical hysterectomy was performed by a hybrid approach of a retractor
      system exerting its effects on lifting the abdominal wall through gravity and
      conventional laparoscopy, thus bypassing the adverse effects of pneumoperitoneum
      on ventilation.

PMID- 24329016
TI  - The Affordable Care Act: a comprehensive and integrated approach to health care.

PMID- 24329015
TI  - Infant negative affect and maternal interactive behavior during the still-face
      procedure: the moderating role of adult attachment states of mind.
AB  - The current study examined associations between attachment state of mind measured
      prenatally (N = 259) and maternal behavior in the reunion episode of the still
      face procedure when infants were six months of age both as a main effect and in
      conjunction with infant negative affect. Using a dimensional approach to adult
      attachment measurement, dismissing and preoccupied states of mind were negatively
      associated with maternal sensitivity, and each correlated with distinct parenting
      behaviors. Positive associations were found between dismissing states of mind and
      maternal monitoring and preoccupied states of mind and maternal withdraw.
      Maternal preoccupation moderated associations between infant negative affect and
      maternal intrusive, withdrawn, and monitoring behaviors, supporting the notion
      that maternal attachment influences parenting behavior via a modulatory process
      in which infant distress cues are selectively filtered and responded to. Analyses
      using a traditional AAI scale and classification approach also provided evidence
      for distinct parenting behavior correlates of insecure adult attachment
      representations. The importance of measuring global and stylistic differences in
      maternal behavior in contexts which allow for the activation of the entire range
      of infant affective states is discussed. 

PMID- 24329017
TI  - Sorting multiple classes in multi-dimensional ROC analysis: parametric and
      nonparametric approaches.
AB  - In large-scale data analysis, such as in a microarray study to identify the most
      differentially expressed genes, diagnostic tests are frequently used to classify
      and predict subjects into their different categories. Frequently, these
      categories do not have an intrinsic natural order even though the quantitative
      test results have a relative order. As identifying the correct order for a proper
      definition of accuracy measures is important for a high-dimensional receiver
      operating characteristic (ROC) analysis, we propose rigorous and automated
      approaches to sort out the multiple categories using simple summary statistics
      such as means and relative effects. We discuss the hypervolume under the ROC
      manifold (HUM), its dependence on the order of the test results and the minimum
      acceptable HUM values in a general multi-category classification problem. Using a
      leukemia data set and a liver cancer data set, we show how our approaches provide
      accurate screening results when we have a large number of tests.

PMID- 24329018
TI  - Endothelial function and carotid intima-media thickness in giant-cell arteritis.
AB  - BACKGROUND: Vascular endothelial dysfunction and intima-media thickness are
      characteristic aspects of several vasculitides. We investigated retrospectively
      the impact of steroid treatment on endothelial dysfunction and intima-media
      thickness in giant-cell arteritis. METHODS: Forty-one patients with giant-cell
      arteritis (28 female and 13 male) underwent flow-mediated dilatation, a marker of
      endothelial function, and carotid intima-media thickness within 24 h after
      diagnosis and 6 months thereafter. Both parameters were investigated in 41
      patients of an age- and gender-matched control group. RESULTS: Brachial flow
      mediated dilatation response at baseline was 3.4% (0.2, 8.0) and 1.7% (0.2, 4.8)
      in giant-cell arteritis patients and control group, respectively. After 6 months
      treatment, flow-mediated dilatation response was 2.8% (0.4, 4.8) in patients with
      giant-cell arteritis (P = 0.066) and 1.4% (0.1, 5.5) in the control group (P =
      0.741). In contrast, mean carotid intima-media thickness of giant-cell arteritis
      patients improved significantly between baseline [1.0 mm (0.79, 1.2)] and 6-month
      follow-up [0.82 mm (0.7, 1.04), P < 0.001]. Subjects with additional symptoms of
      polymyalgia rheumatica had a notable enlargement of carotid intima-media
      thickness [1.23 mm (1.14, 2.09)] compared to giant-cell arteritis patients
      without polymyalgia rheumatica at baseline [0.91 mm (0.76, 1.04), P = 0.001] and
      6-month follow-up [1.16 mm (0.80, 1.26) vs. 0.77 mm (0.68, 0.88), P = 0.009].
      CONCLUSION: Steroid therapy has no influence on endothelial function but does
      significantly improve carotid intima-media thickness in giant-cell arteritis.
      This divergence of endothelial function and intima-media thickness reflects the
      specifity of giant-cell arteritis for cerebrovascular arteries thereby sparing
      the brachial arteries.

PMID- 24329019
TI  - Stereotactic radiosurgery for cerebellopontine angle meningiomas.
AB  - OBJECT: To assess the long-term outcomes of stereotactic radiosurgery (SRS) for
      cerebellopontine angle (CPA) meningiomas, the authors retrospectively reviewed
      data from a 20-year experience. They evaluated progression-free survival as well
      as improvement, stabilization, or deterioration in clinical symptoms. METHODS:
      Seventy-four patients with CPA meningiomas underwent SRS involving various Gamma
      Knife technologies between 1990 and 2010. The most common presenting symptoms
      were dizziness or disequilibrium, hearing loss, facial sensory dysfunction, and
      headache. The median tumor volume was 3.0 cm(3) (range 0.3-17.1 cm(3)), and the
      median radiation dose to the tumor margin was 13 Gy (range 11-16 Gy). The median
      follow-up period was 40 months (range 4-147 months). RESULTS: At last imaging
      follow-up, the tumor volume had decreased in 46 patients (62%), remained stable
      in 26 patients (35%), and increased in 2 patients (3%). The progression-free
      survival after SRS was 98% at 1 year, 98% at 3 years, and 95% at 5 years. At the
      last clinical follow-up, 23 patients (31%) showed neurological improvement, 43
      patients (58%) showed no change in symptoms or signs, and 8 patients (11%) had
      worsening symptoms or signs. The neurological improvement rate after SRS was 16%
      at 1 year, 31% at 3 years, and 40% at 5 years. The post-SRS deterioration rate
      was 5% at 1 year, 10% at 3 years, and 16% at 5 years. A multivariate analysis
      demonstrated that trigeminal neuralgia was the symptom most likely to worsen
      after SRS (HR 0.08, 95% CI 0.02-0.31; p = 0.001). Asymptomatic peritumoral edema
      occurred in 4 patients (5%) after SRS, and symptomatic adverse radiation effects
      developed in 7 patients (9%). CONCLUSIONS: Stereotactic radiosurgery for CPA
      meningiomas provided a high tumor control rate and relatively low risk of ARE.
      Tumor compression of the trigeminal nerve by a CPA meningioma resulted in an
      increased rate of facial pain worsening in this patient experience.

PMID- 24329020
TI  - Atypical meningiomas.

PMID- 24329021
TI  - Intraoperative magnetic resonance imaging and pituitary surgery.

PMID- 24329022
TI  - Advanced neuroimaging findings of pseudotumoral hemicerebellitis in an elderly
      male requiring surgical decompression.
AB  - Acute cerebellitis is an inflammatory process that usually affects bilateral
      cerebellar hemispheres in the pediatric population. Pseudotumoral
      hemicerebellitis is an extremely rare presentation in which unilateral cerebellar
      involvement mimics a tumor that can exert significant mass effect on the
      surrounding structures, which may require surgical intervention. Magnetic
      resonance imaging characteristics that suggest cerebellitis include cerebellar
      swelling, T2 hyperintensity, and pial enhancement. Advanced neuroimaging,
      including MR perfusion and MR spectroscopy, may be helpful in excluding other
      diagnoses. The authors present the case of pseudotumoral hemicerebellitis in the
      oldest documented patient, a 73-year-old man who required surgical decompression,
      and they provide a brief discussion of advanced neuroimaging findings. 

PMID- 24329023
TI  - Determining the utility of intraoperative magnetic resonance imaging for
      transsphenoidal surgery: a retrospective study.
AB  - OBJECT: Intraoperative MRI (iMRI) provides updated information for
      neuronavigational purposes and assessments on the status of resection during
      transsphenoidal surgery (TSS). The high-field technique additionally provides
      information about vascular structures at risk and precise information about
      extrasellar residual tumor, making it readily available during the procedure. The
      imaging, however, extends the duration of surgery. To evaluate the benefit of
      this technique, the authors conducted a retrospective study to compare
      postoperative outcome and residual tumor in patients who underwent conventional
      microsurgical TSS with and without iMRI. METHODS: A total of 143 patients were
      assessed. A cohort of 67 patients who had undergone surgery before introduction
      of iMRI was compared with 76 patients who had undergone surgery since iMRI became
      routine in TSS at the authors' institution. Residual tumor, complications,
      hormone dependency, biochemical remission rates, and improvement of vision were
      assessed at 6-month follow-up. A volumetric evaluation of residual tumor was
      performed in cases of parasellar tumor extension. RESULTS: The majority of
      patients in both groups suffered from nonfunctioning pituitary adenomas. At the 6
      month follow-up assessment, vision improved in 31% of patients who underwent iMRI
      assisted surgery versus 23% in the conventional group. One instance of
      postoperative intrasellar bleeding was found in the conventional group. No major
      complications were found in the iMRI group. Minor complications were seen in 9%
      of patients in the iMRI group and in 5% of those in the conventional group. No
      differences between groups were found for hormone dependency and biochemical
      remission rates. Time of surgery was significantly lower in the conventional
      treatment group. Overall a residual tumor was found after surgery in 35% of the
      iMRI group, and 41% of the conventional surgery group harbored a residual tumor.
      Total resection was achieved as intended significantly more often in the iMRI
      group (91%) than in the conventional group (73%) (p < 0.034). Patients with a
      planned subtotal resection showed higher mean volumes of residual tumor in the
      conventional group. There was a significantly lower incidence of intrasellar
      tumor remnants in the iMRI group than in the conventional group. Progression-free
      survival after 30 months was higher according to Kaplan-Meier analysis with the
      use of iMRI, but a statistically significant difference could not be shown.
      CONCLUSIONS: The use of high-field iMRI leads to a significantly higher rate of
      complete resection. In parasellar tumors a lower residual volume and a
      significantly lower rate of intrasellar tumor remnants were shown with the
      technique. So far, long-term follow-up is limited for iMRI. However, after 2
      years Kaplan-Meier analyses show a distinctly higher progression-free survival in
      the iMRI group. No significant benefit of iMRI was found for biochemical
      remission rates and improvement of vision. Even though the surgical time was
      longer with the adjunct use of iMRI, it did not increase the complication rate
      significantly. The authors therefore recommend routine use of high-field iMRI for
      pituitary surgery, if this technique is available at the particular center.

PMID- 24329024
TI  - Normal dimensions of the posterior pituitary bright spot on magnetic resonance
      imaging.
AB  - OBJECT: The normal pituitary bright spot seen on unenhanced T1-weighted MRI is
      thought to result from the T1-shortening effect of the vasopressin stored in the
      posterior pituitary. Individual variations in its size may be difficult to
      differentiate from pathological conditions resulting in either absence of the
      pituitary bright spot or in T1-hyperintense lesions of the sella. The objective
      of this paper was to define a range of normal dimensions of the pituitary bright
      spot and to illustrate some of the most commonly encountered pathologies that
      result in absence or enlargement of the pituitary bright spot. METHODS: The
      authors selected normal pituitary MRI studies from 106 patients with no pituitary
      abnormality. The size of each pituitary bright spot was measured in the longest
      axis and in the dimension perpendicular to this axis to describe the typical
      dimensions. The authors also present cases of patients with pituitary
      abnormalities to highlight the differences and potential overlap between normal
      and pathological pituitary imaging. RESULTS: All of the studies evaluated were
      found to have pituitary bright spots, and the mean dimensions were 4.8 mm in the
      long axis and 2.4 mm in the short axis. The dimension of the pituitary bright
      spot in the long axis decreased with patient age. The distribution of dimensions
      of the pituitary bright spot was normal, indicating that 99.7% of patients should
      have a pituitary bright spot measuring between 1.2 and 8.5 mm in its long axis
      and between 0.4 and 4.4 mm in its short axis, an interval corresponding to 3
      standard deviations below and above the mean. In cases where the dimension of the
      pituitary bright spot is outside this range, pathological conditions should be
      considered. CONCLUSIONS: The pituitary bright spot should always be demonstrated
      on T1-weighted MRI, and its dimensions should be within the identified normal
      range in most patients. Outside of this range, pathological conditions affecting
      the pituitary bright spot should be considered.

PMID- 24329025
TI  - Auditory brainstem implants.

PMID- 24329026
TI  - Auditory brainstem implants in neurofibromatosis Type 2: is open speech
      perception feasible?
AB  - OBJECT: Patients with bilateral auditory nerve destruction may perceive some
      auditory input with auditory brainstem implants (ABIs). Despite technological
      developments and trials in new stimulation sites, hearing is very variable and of
      limited quality. The goal of this study was to identify advantageous and critical
      factors that influence the quality of auditory function, especially speech
      perception. METHODS: The authors conducted a prospective study on ABI operations
      performed with the aid of multimodality neuromonitoring between 2005 and 2009 in
      18 patients with neurofibromatosis Type 2. Outcome was evaluated by testing word
      recognition (monotrochee-polysyllabic word test at auditory-only mode [MTPa]) and
      open speech perception (Hochmair-Schulz-Moser [HSM] sentence test), both in pure
      auditory mode. The primary outcome was the HSM score at 24 months. The predictive
      meaning of general clinical data, tumor volume, number of active electrodes,
      duration of deafness, and early hearing data was examined. RESULTS: In 16
      successful ABI activations the average score for MTPa was 89% (SD 13%), and for
      HSM it was 41% (SD 32%) at 24 months. There were 2 nonresponders, 1 after
      radiosurgery and the other in an anatomical variant. Direct facial nerve
      reconstruction during the same surgery was followed by successful nerve recovery
      in 2 patients, with a simultaneous very good HSM result. Patients' age, tumor
      extension, and tumor volume were not negative predictors. There was an inverse
      relationship between HSM scores and deafness duration; 50% or higher HSM scores
      were found only in patients with ipsilateral deafness duration up to 24 months.
      The higher the deafness sum of both sides, the less likely that any HSM score
      will be achieved (p = 0.034). In patients with total deafness duration of less
      than 240 months, higher numbers of active electrodes were significantly
      associated with better outcomes. The strongest cross-correlation was identified
      between early MTPa score at 3 months and 24-month HSM outcome. CONCLUSIONS: This
      study documents that open-set speech recognition in pure auditory mode is
      feasible in patients with ABIs. Large tumor volumes do not prevent good outcome.
      Positive preconditions are short ipsilateral and short bilateral deafness periods
      and high number of auditory electrodes. Early ability in pure auditory word
      recognition tests indicates long-term capability of open speech perception.

PMID- 24329027
TI  - The lion's mane sign: surgical results using the bilateral fronto-orbito-nasal
      approach in large and giant anterior skull base meningiomas.
AB  - OBJECT: Concerns about extreme peritumoral edema and its ensuing surgical and
      perioperative complications led the authors to use the bilateral fronto-orbito
      nasal approach to remove midline anterior skull base meningiomas that were larger
      than 4 cm. The authors hypothesize that extreme vasogenic edema exemplified by
      finger-like hyperintensities extending into the bifrontal white matter and
      external capsule and/or the extreme capsule, coined the lion's mane sign (LMS),
      would help identify patients with a challenging postoperative course. They
      hypothesize that the LMS would better predict symptomatic postoperative cerebral
      edema than the edema index (EI). METHODS: This is an observational case series of
      9 patients. The authors noted the grade, pathology, tumor volume, EI, and the
      presence or absence of the LMS in all tumors. They used the intensive unit care
      (ICU) length of stay as a nonspecific measure reflecting postoperative
      symptomatic cerebral edema. Comparisons of edema-related postoperative
      complications and the EI were made between patients with and without an LMS.
      RESULTS: Bifrontal hyperintensities, extending into at least three-eighths of the
      length of the external capsules on T2-weighted MRI, seen in 4 of 9 patients,
      portended a longer postoperative ICU stay. The presence of an LMS better
      predicted postoperative complications related to cerebral edema than tumor grade,
      pathology, volume, or EI. CONCLUSIONS: The LMS predicts an increased duration of
      stay in the ICU after a bilateral fronto-orbito-nasal approach for resection of
      large and giant anterior skull base meningiomas. Furthermore, the LMS better
      predicted increased length of stay in the ICU than did the EI.

PMID- 24329028
TI  - Family building using donated gametes and embryos in the UK: recommendations for
      policy and practice on behalf of the British Infertility Counselling Association
      and the British Fertility Society in collaboration with the Association of
      Clinical Embryologists and the Royal College of Nurses Fertility Nurses Forum.
AB  - The UK Department of Health's consultation on the future of the Human
      Fertilisation and Embryology Authority (HFEA) presented an opportunity to review
      current practice in relation to donor conception (DC) and make recommendations
      for improving services to those seeking fertility treatment, to families with
      donor conceived children and those of donors, and to those seeking later
      information. The year 2023 marks the start of post-2005 donor conceived adults
      having statutory access to identifying information about their donor(s); some
      adults with pre-2005 donors will have access sooner if the donor(s) re-registers
      as 'willing to be identified'. This paper examines current practice in UK
      licensed treatment centres in collecting and disseminating donor information and
      in supporting donors and prospective parents. Further, it considers current HFEA
      functions concerning DC including its responsibilities for the Register of
      Information and Donor Sibling Link and its approach to policy making, regulation
      and the release of information from these Registers to applicants. Proposals for
      how these functions could be carried out in the future are set out together with
      recommendations for national support and intermediary services. The key evidence
      available to support these recommendations is outlined.

PMID- 24329029
TI  - Palladium(II)-catalyzed ortho-olefination of arenes applying sulfoxides as remote
      directing groups.
AB  - A novel palladium-catalyzed ortho-C(sp(2))-H olefination protocol has been
      developed by the use of sulfoxide as the directing group. Importantly, relatively
      remote coordination can be accessed to achieve the ortho olefination of benzyl, 2
      arylethyl, and 3-arylpropenyl sulfoxide substrates, and the olefinated sulfoxide
      can be easily transformed to other functionalities. 

PMID- 24329030
TI  - Engineered Si electrode nanoarchitecture: a scalable postfabrication treatment
      for the production of next-generation Li-ion batteries.
AB  - A novel, economical flash heat treatment of the fabricated silicon based
      electrodes is introduced to boost the performance and cycle capability of Li-ion
      batteries. The treatment reveals a high mass fraction of Si, improved interfacial
      contact, synergistic SiO2/C coating, and a conductive cellular network for
      improved conductivity, as well as flexibility for stress compensation. The
      enhanced electrodes achieve a first cycle efficiency of ~84% and a maximum charge
      capacity of 3525 mA h g(-1), almost 84% of silicon's theoretical maximum.
      Further, a stable reversible charge capacity of 1150 mA h g(-1) at 1.2 A g(-1)
      can be achieved over 500 cycles. Thus, the flash heat treatment method introduces
      a promising avenue for the production of industrially viable, next-generation Li
      ion batteries. 

PMID- 24329031
TI  - Effect of prehospital cardiac catheterization lab activation on door-to-balloon
      time, mortality, and false-positive activation.
AB  - BACKGROUND: Reperfusion of ST elevation myocardial infarction (STEMI) is most
      effective when performed early. Notification of the cardiac catheterization
      laboratory (cath lab) prior to hospital arrival based on paramedic-performed ECGs
      has been proposed as a strategy to decrease time to reperfusion and mortality.
      The purpose of this study was to compare the effects of cath lab activation prior
      to patient arrival versus activation after arrival at the emergency department
      (ED). METHODS: We performed a retrospective cohort study (n = 1933 cases) using
      Los Angeles County STEMI database from May 1, 2008 through August 31, 2009. The
      database includes patients arriving at a STEMI Receiving Center (SRC) by
      ambulance who were diagnosed with STEMI either before or after hospital arrival.
      We compared the cohort of patients with prehospital cath lab activation to those
      activated from the ED within 5 minutes of first ED ECG. Outcomes measured were
      mortality, door-to-balloon time, percent door-to-balloon time <90 min, and
      percentage of false-positive activations. RESULTS: Prehospital cath lab
      activations had mean door-to-balloon times 14 minutes shorter (95% CI 11-17), in
      hospital mortality 1.5% higher (95% CI -1.0-5.2), and false-positive activation
      7.8%, (95% CI 2.7-13.3) higher than ED activation. For prehospital activation,
      93% (95% CI 91-94%) met a door-to-balloon target of 90 minutes versus 85% (95% CI
      80-88%) for ED activations. CONCLUSION: Prehospital cath lab activation based on
      the prehospital ECG was associated with decreased door-to-balloon times but did
      not affect hospital mortality. False-positive activation was common and occurred
      more often with prehospital STEMI diagnosis.

PMID- 24329032
TI  - A comparison of the prehospital motor component of the Glasgow coma scale (mGCS)
      to the prehospital total GCS (tGCS) as a prehospital risk adjustment measure for
      trauma patients.
AB  - OBJECTIVE: This study compared the prehospital motor component subscale of the
      Glasgow Coma Scale (mGCS) to the prehospital total GCS (tGCS) score for its
      ability to predict the need for intubation, survival to hospital discharge, and
      neurosurgical intervention in trauma patients. METHODS: This is a retrospective
      analysis of an urban level 1 trauma registry. All trauma patients presenting to
      the trauma center emergency department via emergency medical services from July
      2008 through June 2010 were included. The area under the receiver operating
      characteristics curve (AUC) analysis was used to compare the predictive ability
      of the prehospital mGCS to tGCS for three outcomes: intubation, survival to
      hospital discharge, and neurosurgical intervention. Two subgroups (patients with
      injury severity score [ISS] >= 16 and traumatic brain injury [TBI] [head
      abbreviated injury score (AIS) >= 3]) were analyzed. An a priori statistically
      significant absolute difference of 0.050 in AUC between mGCS and tGCS for these
      clinical outcomes was used as a clinically significant difference. Multiple
      imputation was used for missing prehospital GCS data. RESULTS: There were 9,816
      patients, of which 4% were intubated, 3.8% had neurosurgical intervention, and
      97.1% survived to hospital discharge. The absolute difference in AUC (prehospital
      tGCS minus mGCS) for all cases was statistically significant for all three
      outcomes but did not reach the clinical significance threshold: survival = 0.010
      (95% CI: 0.002-0.018), intubation = 0.018 (95% CI: 0.011-0.024), and
      neurosurgical intervention = 0.019 (95% CI: 0.007-0.029). The difference in AUC
      between tGCS and mGCS for the subgroups ISS >= 16 (n = 1,151) and TBI (n = 1,165)
      did not reach clinical significance for the three outcomes. The discriminatory
      ability of the prehospital mGCS was good for survival (AUC: all patients = 0.89,
      ISS >= 16 = 0.84, traumatic brain injury = 0.86) excellent for intubation (AUC:
      all patients = 0.95, ISS >= 16 = 0.91, traumatic brain injury = 0.91), and poor
      for neurosurgical intervention (AUC: all patients = 0.67, ISS >= 16 = 0.57,
      traumatic brain injury = 0.60). CONCLUSION: The prehospital mGCS appears have
      good discriminatory power and is equivalent to the prehospital tGCS for
      predicting intubation and survival to hospital discharge in this trauma
      population as a whole, those with ISS >= 16, or TBI.

PMID- 24329034
TI  - Verbal creativity in semantic variant primary progressive aphasia.
AB  - Emergence of visual and musical creativity in the setting of neurologic disease
      has been reported in patients with semantic variant primary progressive aphasia
      (svPPA), also called semantic dementia (SD). It is hypothesized that loss of left
      anterior frontotemporal function facilitates activity of the right posterior
      hemispheric structures, leading to de novo creativity observed in visual artistic
      representation. We describe creativity in the verbal domain, for the first time,
      in three patients with svPPA. Clinical presentations are carefully described in
      three svPPA patients exhibiting verbal creativity, including neuropsychology,
      neurologic exam, and structural magnetic resonance imaging (MRI). Voxel-based
      morphometry (VBM) was performed to quantify brain atrophy patterns in these
      patients against age-matched healthy controls. All three patients displayed new
      onset creative writing behavior and produced extensive original work during the
      course of disease. Patient A developed interest in wordplay and generated a large
      volume of poetry. Patient B became fascinated with rhyming and punning. Patient C
      wrote and published a lifestyle guidebook. An overlap of their structural MR
      scans showed uniform sparing in the lateral portions of the language-dominant
      temporal lobe (superior and middle gyri) and atrophy in the medial temporal
      cortex (amygdala, limbic cortex). New-onset creativity in svPPA may represent a
      paradoxical functional facilitation. A similar drive for production is found in
      visually artistic and verbally creative patients. Mirroring the imaging findings
      in visually artistic patients, verbal preoccupation and creativity may be
      associated with medial atrophy in the language-dominant temporal lobe, but
      sparing of lateral dominant temporal and non-dominant posterior cortices. 

PMID- 24329036
TI  - Hyporeflective pagetoid cells: a new clue for amelanotic melanoma diagnosis by
      reflectance confocal microscopy.
AB  - BACKGROUND: Amelanotic melanoma represents a diagnostic challenge both clinically
      and dermoscopically. Few studies based on case series have explored the
      possibility of using reflectance confocal microscopy (RCM) to diagnose amelanotic
      melanoma. OBJECTIVES: To validate a new confocal feature, named hyporeflective
      pagetoid cells (HPCs), for the diagnosis of amelanotic melanoma. METHODS: A group
      of 20 amelanotic melanomas and a control population of nonpigmented melanocytic
      naevi (10), hypo/nonpigmented nonmelanocytic lesions (20) and pigmented melanomas
      (20), imaged by RCM, were retrospectively evaluated. The presence of HPCs and
      other diagnosis-specific confocal features was assessed and correlated with
      histopathology. RESULTS: HPCs were present, and usually abundant, in the majority
      of amelanotic melanomas (85%). As expected, they were also observed in Spitz
      naevi. On histopathology, they were correlated with pagetoid infiltration of
      hypomelanotic melanocytes in all melanocytic lesions. Few nonmelanocytic lesions
      (three squamous cell carcinomas, two seborrhoeic keratoses and one basal cell
      carcinoma) showed the presence of HPCs. In these cases, they corresponded to
      enlarged or dyskeratotic keratinocytes by histopathology. CONCLUSIONS: The
      identification of HPCs in the epidermis is a new parameter that is frequently
      found in amelanotic melanoma. Possible confounders are represented by atypical
      keratinocytes that can be present in nonmelanocytic lesions. However, the whole
      architecture and the presence of additional diagnostic criteria should be
      considered in order to obtain a correct diagnosis.

PMID- 24329035
TI  - Investigational peptide and peptidomimetic MU and delta opioid receptor agonists
      in the relief of pain.
AB  - INTRODUCTION: Current methods for treating prolonged and neuropathic pain are
      inadequate and lead to toxicities that greatly diminish quality of life.
      Therefore, new approaches to the treatment of pain states are needed to address
      these problems. AREAS COVERED: The review primarily reviews approaches that have
      been taken in the peer-reviewed literature of multivalent ligands that interact
      with both MU and delta opioid receptors as agonists, and in some cases, also with
      pharmacophores for antagonist ligands that interact with other receptors as
      antagonists to block pain. EXPERT OPINION: Although there are a number of drugs
      currently on the market for the treatment of pain; none of them are 100%
      successful. In the authors' opinion, it is clear that new directions and
      modalities are needed to better address the treatment of prolonged and
      neuropathic pain; one drug or class clearly is not the answer for all pain
      therapy. Undoubtedly, there are many different phenotypes of prolonged and
      neuropathic pain and this should be one avenue to further develop appropriate
      therapies.

PMID- 24329037
TI  - Psychopathy and the cinema: fact or fiction?
AB  - The authors investigated the relationship between cinema and psychopathy to
      describe and analyze the portrayal of fictional psychopathic characters in
      popular films and over cinematic history. From 400 films (1915-2010), 126
      fictional psychopathic characters (21 female and 105 male) were selected based on
      the realism and clinical accuracy of their profiles. Movies were then analyzed by
      senior forensic psychiatrists and cinema critics. Secondary (71%) and
      manipulative (48%) subtypes were the most common in the female group, while
      secondary (51%) and prototypical (34%) were the most common in the male group.
      Corresponding to the increased understanding of clinical psychopathy by
      professional mental health providers over time, the clinical description of and
      epidemiological data on fictional psychopaths in popular films have become more
      realistic. Realistic fictional psychopaths remain in the minority but are very
      important for didactic purposes in Academic facilities, as "teaching Movies." 

PMID- 24329039
TI  - The Affordable Care Act for behavioral health consumers and families.
AB  - The Affordable Care Act (ACA) is legislation that might ultimately make health
      insurance coverage available to all Americans. The ACA is scheduled for full
      implementation in 2014. Many decisions are still being made concerning
      implementation. Provisions of the ACA are of paramount importance to persons with
      mental illnesses and substance use disorders. This is a brief overview of key
      elements of the ACA and potential effects on consumers of behavioral health
      services and their families. Behavioral health consumers and their families
      include persons with mental illnesses, as well as persons with substance use
      disorders, and their families. 

PMID- 24329040
TI  - The safety and efficacy of adalimumab in patients with Crohn's disease: the
      experience of a single Canadian tertiary care centre.
AB  - BACKGROUND. Adalimumab (ADA), an antitumor necrosis factor (anti-TNF) monoclonal
      antibody, is effective in treating moderate-to-severely active Crohn's disease
      (CD). ADA has been associated with a variety of adverse events (AE). The purpose
      of this study is to determine the safety and efficacy of ADA in CD patients in
      clinical practice. METHODS. A retrospective analysis was performed on CD patients
      treated with ADA. Data extracted and analyzed included patient and CD
      demographics, remission and response rates with ADA, and safety and tolerability
      of ADA. RESULTS. A total of 149 ADA-treated CD patients were included. The mean
      duration of therapy with ADA was 20 months with 32% of patients discontinuing
      treatment. Anti-TNF-naive and anti-TNF-exposed patients on ADA achieved clinical
      remission in 45% and 32%, had a clinical response in 23% and 23%, and had no
      clinical response in 32% and 45%, respectively. Anti-TNF-naive and anti-TNF
      exposed patients maintained remission in 82% and 67%, respectively. Fistulas
      healed in 19% and improved in 19%. AE occurred in 38% of patients with infection
      being the most common (20%). Serious infections lead to death in one (<1%).
      Logistic regression of AE did not identify statistically significant predictors
      except for colonic disease location (odds ratio [OR] = 0.31, 95% CI = 0.12-0.82,
      p = 0.018) and the rate of ADA discontinuation (OR = 3.24, 95% CI = 1.58-6.64, p
      = 0.0013). CONCLUSION. ADA is an effective treatment for CD. AE can occur
      commonly leading to discontinuation of medication and may be influenced by
      disease location. Although serious complications are rare, close monitoring of
      all patients on ADA is needed.

PMID- 24329038
TI  - Mitochondrial translocation of p53 modulates neuronal fate by preventing
      differentiation-induced mitochondrial stress.
AB  - AIMS: Apoptosis regulatory proteins, such as p53, play a pivotal role in neural
      differentiation, through mechanisms independent of cell death. In addition, p53
      has been identified as an important regulator of mitochondrial survival response,
      maintaining mitochondrial DNA (mtDNA) integrity and oxidative protection. The aim
      of this study was to determine the role of mitochondrial p53 in organelle damage
      and neural differentiation. RESULTS: Our results show that mitochondrial
      apoptotic events such as reactive oxygen species production, mitochondrial
      membrane permeabilization, and cytochrome c release are typical of early-stage
      mouse neural stem cell differentiation, which occurs 3-18 h after induction of
      differentiation, with no evidence of cell death. In addition, decreased mtDNA
      content, lipidated LC3 (LC3-II), colocalization of mitochondria and LC3-II
      puncta, and mitochondria-associated Parkin are consistent with activation of
      mitophagy. Importantly, at early stages of neural differentiation, p53 was
      actively translocated to mitochondria and attenuated mitochondrial oxidative
      stress, cytochrome c release, and mitophagy. Forced mitochondrial translocation
      of p53 increased neurogenic potential and neurite outgrowth. INNOVATION AND
      CONCLUSION: In conclusion, our results reveal a novel role for mitochondrial p53,
      which modulates mitochondrial damage and apoptosis-related events in the context
      of neural differentiation, thus enhancing neuronal fate.

PMID- 24329043
TI  - AAI predicts patients' in-session interpersonal behavior and discourse: a "move
      to the level of the relation" for attachment-informed psychotherapy research.
AB  - There is currently little empirical evidence regarding how patients' attachment
      patterns manifest in individual psychotherapy. This study compared the in-session
      discourse of patients classified secure, dismissing, and preoccupied on the Adult
      Attachment Interview (AAI). Rather than focusing on content or form alone, this
      study analyzed how patients' discourse elicits and maintains emotional proximity
      with the therapist. The AAI was administered to 56 patients prior to treatment
      and one session for each patient was rated with the Patient Attachment Coding
      System (PACS) by four independent raters, blind to patients' AAI classification.
      Significant differences were found in the discourse of patients with different
      attachment patterns. Namely, secure and preoccupied patients showed more contact
      seeking behavior than dismissing patients, who avoided emotional proximity more,
      while preoccupied patients resisted therapists' help more than did secure and
      dismissing patients. These results suggest that the different attachment patterns
      may have distinctive manifestations in the psychotherapy process that can be
      tracked by external observers. 

PMID- 24329041
TI  - Common errors in multidrug-resistant tuberculosis management.
AB  - Multidrug-resistant tuberculosis (MDR-TB), defined as being resistant to at least
      rifampicin and isoniazid, has an increasing burden and threatens TB control.
      Diagnosis is limited and usually delayed while treatment is long lasting, toxic
      and poorly effective. MDR-TB management in scarce-resource settings is demanding
      however it is feasible and extremely necessary. In these settings, cure rates do
      not usually exceed 60-70% and MDR-TB management is novel for many TB programs. In
      this challenging scenario, both clinical and programmatic errors are likely to
      occur. The majority of these errors may be prevented or alleviated with
      appropriate and timely training in addition to uninterrupted procurement of high
      quality drugs, updated national guidelines and laws and an overall improvement in
      management capacities. While new tools for diagnosis and shorter and less toxic
      treatment are not available in developing countries, MDR-TB management will
      remain complex in scarce resource settings. Focusing special attention on the
      common errors in diagnosis, regimen design and especially treatment delivery may
      benefit patients and programs with current outdated tools. The present article is
      a compilation of typical errors repeatedly observed by the authors in a wide
      range of countries during technical assistant missions and trainings. 

PMID- 24329044
TI  - Association of aggressive periodontitis with reduced erythrocyte counts and
      reduced hemoglobin levels.
AB  - BACKGROUND AND OBJECTIVE: Studies have shown that erythrocyte counts and
      hemoglobin levels are reduced in patients with chronic periodontitis, suggesting
      that this condition may be associated with anemia of chronic disease. Although
      increased leukocyte counts have been reported in aggressive periodontitis, very
      little is known about the effects of aggressive periodontitis on erythrocyte
      counts. The present study was undertaken to determine whether generalized
      aggressive periodontitis is associated with reduced erythrocyte counts and
      reduced hemoglobin levels. MATERIAL AND METHODS: The present study was conducted
      as a case-control study in which 64 patients with generalized aggressive
      periodontitis were categorized as cases and 58 periodontally healthy individuals
      were categorized as controls. Erythrocyte parameters (such as erythrocyte count,
      hemoglobin concentration, and hematocrit and erythrocyte indices) and clinical
      parameters (such as gingival index, plaque index, probing depth, clinical
      attachment level and percentage of severe sites) were recorded. RESULTS:
      Significant differences were observed between cases and controls in mean
      erythrocyte count (4.45 +/- 0.6 * 10(6) erythrocytes/MUL and 4.78 +/- 0.56 *
      10(6) erythrocytes/MUL respectively, p = 0.002) and hemoglobin level (12.43 +/-
      1.83 g/dL and 13.53 +/- 1.64 g/dL, respectively, p = 0.001). Other erythrocyte
      parameters, such as hematocrit, mean corpuscular volume and mean corpuscular
      hemoglobin, were also significantly lower among cases compared with controls.
      Logistic regression analyses showed that generalized aggressive periodontitis was
      significantly associated with lower erythrocyte counts ( p = 0.032) and a lower
      hemoglobin concentration ( p = 0.017). CONCLUSION: The findings of the present
      study suggest that patients with generalized aggressive periodontitis tend to
      have lower erythrocyte counts and lower hemoglobin levels compared with
      periodontally healthy controls. This suggests that generalized aggressive
      periodontitis, like chronic periodontitis, may be associated with a risk for
      anemia of chronic disease.

PMID- 24329045
TI  - Influence of the utilization time of different manual toothbrushes on oral
      hygiene assessed during a 6-month observation period: a randomized clinical
      trial.
AB  - BACKGROUND: The aim of this randomized clinical trial (RCT) was to investigate
      whether 6-month continuous use of different manual toothbrushes (TBs) influences
      plaque removal and the degree of gingival inflammation compared to short
      utilization periods of 4 weeks each. METHODS: In total, 96 participants were
      randomly allocated into two groups: continuous use during 6 months (non-renewal
      group) or a change in TB every 4 weeks during 6 months (renewal group). Each
      group was subdivided into four subgroups (groups A to H; n = 12 each) according
      to the head size (normal or short) and bristle hardness (medium or soft) of the
      TB used. The modified Quigley-Hein plaque index (QHI), papilla bleeding index
      (PBI), and gingival index (GI) were recorded at baseline and 2, 8, 12, 16, and 24
      weeks after baseline. After 24 weeks, each participant received a new TB, and at
      week 26, the final QHI, PBI, and GI were determined. The statistical evaluation
      consisted of analysis of covariance (P <0.05). RESULTS: With time, QHI, PBI, and
      GI were significantly different between the renewal and the non-renewal groups
      (QHI: P = 0.02; PBI: P = 0.04; GI: P <0.01), independent of subgroup. In the
      renewal group, QHI showed a significant decrease between baseline and each follow
      up visit (P <0.01). In the non-renewal group, there was a significant decrease
      compared to baseline up to and including week 16 (P <0.01). PBI in the renewal
      group showed no significant differences between baseline and each follow-up visit
      (P >0.05). In the non-renewal group, only the normal head/soft subgroup exhibited
      a significant increase at week 24 (P = 0.02). The GI in the renewal group showed
      no difference between baseline and all follow-up visits, whereas in the non
      renewal group, there was a significant decrease up to and including week 12 (P
      <0.05). CONCLUSIONS: Six-month continuous use reduced the effectiveness of the TB
      with respect to plaque removal, and gingival inflammation appeared to increase.

PMID- 24329047
TI  - Communication: a new paradigm for structure prediction in multicomponent systems.
AB  - We analyse the combinatorial aspect of global optimisation for multicomponent
      systems, which involves searching for the optimal chemical ordering by permuting
      particles corresponding to different species. The overall composition is presumed
      fixed, and the geometry is relaxed after each permutation in order to relieve
      local strain. From ideas used to solve graph partitioning problems we devise a
      deterministic search scheme that outperforms (by orders of magnitude)
      conventional and self-guided basin-hopping global optimisation. The search is
      guided by the energy gain from either swapping particles i and j (DeltaEij) or
      changing the identity of particles i (DeltaEi). These quantities are derived from
      the underlying (arbitrary) energy function, hence not constituting external bias,
      and for site-separable force fields each DeltaEi can be approximated simply and
      efficiently. In our self-guided variant of basin-hopping, particles are weighted
      by an approximate DeltaEi when randomly selected for an exchange, yielding a
      significant improvement for segregated multicomponent systems with modest
      particle size mismatch. 

PMID- 24329048
TI  - Communication: angular momentum alignment and fluorescence polarization of alkali
      atoms photodetached from helium nanodroplets.
AB  - The theory of photofragments angular momentum polarization is applied to the
      photodetachment of an electronically excited alkali atom from a helium
      nanocluster (N = 200). The alignment of the electronic angular momentum of the
      bare excited alkali atoms produced is calculated quantum mechanically by solving
      the excited states coupled equations with potentials determined by density
      functional theory (DFT). Pronounced oscillations as a function of excitation
      energy are predicted for the case of Na@(He)200, in marked contrast with the
      absorption cross-section and angular distribution of the ejected atoms which are
      smooth functions of the energy. These oscillations are due to quantum
      interference between different coherently excited photodetachment pathways.
      Experimentally, these oscillations should be reflected in the fluorescence
      polarization and polarization-resolved photoelectron yield of the ejected atoms,
      which are proportional to the electronic angular momentum alignment. In addition,
      this result is much more general than the test case of NaHe200 studied here. It
      should be observable for larger droplets, for higher excited electronic states,
      and for other alkali as well as for alkali-earth atoms. Detection of these
      oscillations would show that the widely used pseudo-diatomic model can be valid
      beyond the prediction of absorption spectra and could help in interpreting parts
      of the dynamics, as already hinted by some experimental results on angular
      anisotropy of bare alkali fragments. 

PMID- 24329046
TI  - Age-related differences in the dynamic architecture of intrinsic networks.
AB  - Correlations among low-frequency spontaneous fluctuations in the blood oxygen
      level-dependent (BOLD) signal reflect the connectivity of intrinsic large-scale
      networks in the brain. These correlations have typically been characterized over
      the entire timecourse (mean connectivity), but the mean correlations between
      regions vary dynamically. By focusing on the linear relationship between activity
      in network nodes within the default mode network (DMN), dorsal attention network
      (DAN), and fronto-parietal task control network (FPTC) captured by their inter
      correlations, we demonstrate that this dynamic pattern of fluctuations reveals a
      detailed substructure, that this substructure is robust across individuals, and
      that the expression of specific factors is correlated with age. To do this, we
      conducted a chained P-technique factor analysis of the correlations in
      nonoverlapping temporal windows across N=145 normal aging subjects (age 56-89).
      The expression of factors within the DMN, FPTC, and DAN was highly correlated
      with age: Decreased intercorrelations within nodes in each factor were correlated
      with advanced age. Although these findings converge with those from stationary
      analysis, the ability to quantify age-related changes in the coherence of
      fluctuating connectivity may yield more insights into age-related cognitive
      decline.

PMID- 24329049
TI  - Communication: theoretical study of ThO for the electron electric dipole moment
      search.
AB  - An experiment to search for the electron electric dipole moment (eEDM) on the
      metastable H(3)Delta1 state of ThO molecule was proposed and now prepared by the
      ACME Collaboration [http://www.electronedm.org]. To interpret the experiment in
      terms of eEDM and dimensionless constant kT, P characterizing the strength of the
      T,P-odd pseudoscalar-scalar electron-nucleus neutral current interaction, an
      accurate theoretical study of an effective electric field on electron, Eeff, and
      a parameter of the T,P-odd pseudoscalar-scalar interaction, WT, P, in ThO is
      required. We report our results for Eeff (84 GV/cm) and WT, P (116 kHz) together
      with the hyperfine structure constant, molecule frame dipole moment, and
      H(3)Delta1 -> X(1)Sigma(+) transition energy, which can serve as a measure of
      reliability of the obtained Eeff and WT, P values. Besides, our results include a
      parity assignment and evaluation of the electric-field dependence for the
      magnetic g factors in the Omega-doublets of H(3)Delta1. 

PMID- 24329050
TI  - Tensor decomposition in post-Hartree-Fock methods. II. CCD implementation.
AB  - In a previous publication, we have discussed the usage of tensor decomposition in
      the canonical polyadic (CP) tensor format for electronic structure methods.
      There, we focused on two-electron integrals and second order Moller-Plesset
      perturbation theory (MP2). In this work, we discuss the CP format for Coupled
      Cluster (CC) theory and present a pilot implementation for the Coupled Cluster
      Doubles method. We discuss the iterative solution of the CC amplitude equations
      using tensors in CP representation and present a tensor contraction scheme that
      minimizes the effort necessary for the rank reductions during the iterations.
      Furthermore, several details concerning the reduction of complexity of the
      algorithm, convergence of the CC iterations, truncation errors, and the choice of
      threshold for chemical accuracy are discussed.

PMID- 24329051
TI  - Approaching the complete-basis limit with a truncated many-body expansion.
AB  - High-accuracy electronic structure calculations with correlated wave functions
      demand the use of large basis sets and complete-basis extrapolation, but the
      accuracy of fragment-based quantum chemistry methods has most often been
      evaluated using double-zeta basis sets, with errors evaluated relative to a
      supersystem calculation using the same basis set. Here, we examine the
      convergence towards the basis-set limit of two- and three-body expansions of the
      energy, for water clusters and ion-water clusters, focusing on calculations at
      the level of second-order Moller-Plesset perturbation theory (MP2). Several
      different corrections for basis-set superposition error (BSSE), each consistent
      with a truncated many-body expansion, are examined as well. We present a careful
      analysis of how the interplay of errors (from all sources) influences the
      accuracy of the results. We conclude that fragment-based methods often benefit
      from error cancellation wherein BSSE offsets both incompleteness of the basis set
      as well as higher-order many-body effects that are neglected in a truncated many
      body expansion. An n-body counterpoise correction facilitates smooth
      extrapolation to the MP2 basis-set limit, and at n = 3 affords accurate results
      while requiring calculations in subsystems no larger than trimers.

PMID- 24329052
TI  - Wavelet analysis of molecular dynamics: efficient extraction of time-frequency
      information in ultrafast optical processes.
AB  - New experimental techniques based on nonlinear ultrafast spectroscopies have been
      developed over the last few years, and have been demonstrated to provide powerful
      probes of quantum dynamics in different types of molecular aggregates, including
      both natural and artificial light harvesting complexes. Fourier transform-based
      spectroscopies have been particularly successful, yet "complete" spectral
      information normally necessitates the loss of all information on the temporal
      sequence of events in a signal. This information though is particularly important
      in transient or multi-stage processes, in which the spectral decomposition of the
      data evolves in time. By going through several examples of ultrafast quantum
      dynamics, we demonstrate that the use of wavelets provide an efficient and
      accurate way to simultaneously acquire both temporal and frequency information
      about a signal, and argue that this greatly aids the elucidation and
      interpretation of physical process responsible for non-stationary spectroscopic
      features, such as those encountered in coherent excitonic energy transport. 

PMID- 24329053
TI  - Orbital-free bond breaking via machine learning.
AB  - Using a one-dimensional model, we explore the ability of machine learning to
      approximate the non-interacting kinetic energy density functional of diatomics.
      This nonlinear interpolation between Kohn-Sham reference calculations can (i)
      accurately dissociate a diatomic, (ii) be systematically improved with increased
      reference data and (iii) generate accurate self-consistent densities via a
      projection method that avoids directions with no data. With relatively few
      densities, the error due to the interpolation is smaller than typical errors in
      standard exchange-correlation functionals. 

PMID- 24329054
TI  - Double, Rydberg and charge transfer excitations from pairing matrix fluctuation
      and particle-particle random phase approximation.
AB  - Double, Rydberg, and charge transfer (CT) excitations have been great challenges
      for time-dependent density functional theory (TDDFT). Starting from an (N +/- 2)
      electron single-determinant reference, we investigate excitations for the N
      electron system through the pairing matrix fluctuation, which contains
      information on two-electron addition/removal processes. We adopt the particle
      particle random phase approximation (pp-RPA) and the particle-particle Tamm
      Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and
      then determine excitation energies by the differences of two-electron
      addition/removal energies. This approach captures all types of interesting
      excitations: single and double excitations are described accurately, Rydberg
      excitations are in good agreement with experimental data and CT excitations
      display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a
      computational cost similar to TDDFT and consequently are promising for practical
      calculations. 

PMID- 24329055
TI  - Ensemble simulations with discrete classical dynamics.
AB  - For discrete classical Molecular Dynamics (MD) obtained by the "Verlet" algorithm
      (VA) with the time increment h there exists (for sufficiently small h) a shadow
      Hamiltonian H with energy E(h), for which the discrete particle positions lie on
      the analytic trajectories for H. The first order estimate of E(h) is employed to
      determine the relation with the corresponding energy, E, for the analytic
      dynamics with h = 0 and the zero-order estimate E0(h) of the energy for discrete
      dynamics, appearing in the literature for MD with VA. We derive a corresponding
      time reversible VA algorithm for canonical dynamics for the (NVT(h)) ensemble and
      determine the relations between the energies and temperatures for the different
      ensembles, including the (NVE0(h)) and (NVT0(h)) ensembles. The differences in
      the energies and temperatures are proportional with h(2) and they are of the
      order of a few tenths of a percent for a traditional value of h. The relations
      between (NVE(h)) and (NVE), and (NVT(h)) and (NVT) are easily determined for a
      given density and temperature, and allow for using larger time increments in MD.
      The accurate determinations of the energies are used to determine the kinetic
      degrees of freedom in a system of N particles. It is 3N - 3 for a three
      dimensional system. The knowledge of the degrees of freedom is necessary when
      simulating small system, e.g., at nucleation. 

PMID- 24329056
TI  - Domain of validity of the perturbative approach to femtosecond optical
      spectroscopy.
AB  - We have performed numerical nonperturbative simulations of transient absorption
      pump-probe responses for a series of molecular model systems. The resulting
      signals as a function of the laser field strength and the pump-probe delay time
      are compared with those obtained in the perturbative response function formalism.
      The simulations and their theoretical analysis indicate that the perturbative
      description remains valid up to moderately strong laser pulses, corresponding to
      a rather substantial depopulation (population) of the initial (final) electronic
      states. 

PMID- 24329057
TI  - The weak-correlation limits of few-electron harmonium atoms.
AB  - The weak-correlation asymptotics of electronic properties of harmonium atoms
      comprising up to four electrons are investigated. In particular, closed-form
      expressions are derived for the first- and second-order contributions to the
      Hartree-Fock and correlation energies of eight electronic states that include
      three singlets, one doublet, two triplets, one quartet, and one quintet, six of
      which are singly determinantal and two are multi-determinantal. This diversity of
      states offers a much richer set of benchmarking tools for calibration of
      approximate electron-correlation methods than the previously published data. The
      availability of the computed energy contributions due to individual spinorbitals
      and their pairs present in the dominant Slater determinants further enhances the
      utility of these benchmarks. 

PMID- 24329058
TI  - The fluctuation-dissipation theorem for stochastic kinetics--implications on
      genetic regulations.
AB  - The Fluctuation-Dissipation theorem (FDT) connects the "memory" in the
      fluctuation in equilibrium to the response of a system after a perturbation,
      which has been a fundamental ground in many branches of physics. When viewing a
      cell as a stochastic biochemical system, the cell's response under a perturbation
      is related to its intrinsic steady-state correlation functions via the FDT, a
      theorem we derived and present in this work. FDT allows us to use the noise to
      derive dynamic response and infer dynamic properties in the system. We tested
      FDT's validity with gene regulation models and found that it is limited to the
      linear response. For an indirect regulation pathway where unknown components may
      exist, FDT still works within the linear response region. Thus, FDT may be used
      for systems with partial knowledge, and it is potentially possible to identify
      the existence of unobserved components. With FDT, the dynamic response can be
      composed of steady-state measurements without the complete detailed knowledge for
      the regulation or kinetics. The response function derived can give important
      insights into the dynamics and time scales of the system. 

PMID- 24329059
TI  - Excited electronic states from a variational approach based on symmetry-projected
      Hartree-Fock configurations.
AB  - Recent work from our research group has demonstrated that symmetry-projected
      Hartree-Fock (HF) methods provide a compact representation of molecular ground
      state wavefunctions based on a superposition of non-orthogonal Slater
      determinants. The symmetry-projected ansatz can account for static correlations
      in a computationally efficient way. Here we present a variational extension of
      this methodology applicable to excited states of the same symmetry as the ground
      state. Benchmark calculations on the C2 dimer with a modest basis set, which
      allows comparison with full configuration interaction results, indicate that this
      extension provides a high quality description of the low-lying spectrum for the
      entire dissociation profile. We apply the same methodology to obtain the full low
      lying vertical excitation spectrum of formaldehyde, in good agreement with
      available theoretical and experimental data, as well as to a challenging model
      C2v insertion pathway for BeH2. The variational excited state methodology
      developed in this work has two remarkable traits: it is fully black-box and will
      be applicable to fairly large systems thanks to its mean-field computational
      cost. 

PMID- 24329060
TI  - Time-dependent density functional theory quantum transport simulation in non
      orthogonal basis.
AB  - Basing on the earlier works on the hierarchical equations of motion for quantum
      transport, we present in this paper a first principles scheme for time-dependent
      quantum transport by combining time-dependent density functional theory (TDDFT)
      and Keldysh's non-equilibrium Green's function formalism. This scheme is beyond
      the wide band limit approximation and is directly applicable to the case of non
      orthogonal basis without the need of basis transformation. The overlap between
      the basis in the lead and the device region is treated properly by including it
      in the self-energy and it can be shown that this approach is equivalent to a lead
      device orthogonalization. This scheme has been implemented at both TDDFT and
      density functional tight-binding level. Simulation results are presented to
      demonstrate our method and comparison with wide band limit approximation is made.
      Finally, the sparsity of the matrices and computational complexity of this method
      are analyzed. 

PMID- 24329061
TI  - Criteria for the accuracy of small polaron quantum master equation in simulating
      excitation energy transfer dynamics.
AB  - The small polaron quantum master equation (SPQME) proposed by Jang et al. [J.
      Chem. Phys. 129, 101104 (2008)] is a promising approach to describe coherent
      excitation energy transfer dynamics in complex molecular systems. To determine
      the applicable regime of the SPQME approach, we perform a comprehensive
      investigation of its accuracy by comparing its simulated population dynamics with
      numerically exact quasi-adiabatic path integral calculations. We demonstrate that
      the SPQME method yields accurate dynamics in a wide parameter range. Furthermore,
      our results show that the accuracy of polaron theory depends strongly upon the
      degree of exciton delocalization and timescale of polaron formation. Finally, we
      propose a simple criterion to assess the applicability of the SPQME theory that
      ensures the reliability of practical simulations of energy transfer dynamics with
      SPQME in light-harvesting systems. 

PMID- 24329062
TI  - A new ab initio potential energy surface for the collisional excitation of HCN by
      para- and ortho-H2.
AB  - We present a new four-dimensional potential energy surface for the collisional
      excitation of HCN by H2. Ab initio calculations of the HCN-H2 van der Waals
      complex, considering both molecules as rigid rotors, were carried out at the
      explicitly correlated coupled cluster with single, double, and perturbative
      triple excitations [CCSD(T)-F12a] level of theory using an augmented correlation
      consistent triple zeta (aVTZ) basis set. The equilibrium structure is linear HCN
      H2 with the nitrogen pointing towards H2 at an intermolecular separation of 7.20
      a0. The corresponding well depth is -195.20 cm(-1). A secondary minimum of 
      183.59 cm(-1) was found for a T-shape configuration with the H of HCN pointing to
      the center of mass of H2. We also determine the rovibrational energy levels of
      the HCN-para-H2 and HCN-ortho-H2 complexes. The calculated dissociation energies
      for the para and ortho complexes are 37.79 cm(-1) and 60.26 cm(-1), respectively.
      The calculated ro-vibrational transitions in the HCN-H2 complex are found to
      agree by more than 0.5% with the available experimental data, confirming the
      accuracy of the potential energy surface. 

PMID- 24329063
TI  - Anharmonic rovibrational calculations of singlet cyclic C4 using a new ab initio
      potential and a quartic force field.
AB  - We report a CCSD(T)/cc-pCV5Z quartic force field (QFF) and a semi-global CCSD(T)
      F12b/aug-cc-pVTZ potential energy surface (PES) for singlet, cyclic C4.
      Vibrational fundamentals, combinations, and overtones are obtained using
      vibrational second-order perturbation theory (VPT2) and the vibrational
      configuration-interaction (VCI) approach. Agreement is within 10 cm(-1) between
      the VCI calculated fundamentals on the QFF and PES using the MULTIMODE (MM)
      program, and VPT2 and VCI results agree for the fundamentals. The agreement
      between VPT2-QFF and MM-QFF results is also good for the C4 combinations and
      overtones. The J = 1 and J = 2 rovibrational energies are reported from both VCI
      (MM) on the PES and VPT2 on the QFF calculations. The spectroscopic constants of
      (12)C4 and two C2v-symmetry, single (13)C-substituted isotopologues are
      presented, which may help identification of cyclic C4 in future experimental
      analyses or astronomical observations. 

PMID- 24329064
TI  - Approximate photochemical dynamics of azobenzene with reactive force fields.
AB  - We have fitted reactive force fields of the ReaxFF type to the ground and first
      excited electronic states of azobenzene, using global parameter optimization by
      genetic algorithms. Upon coupling with a simple energy-gap transition probability
      model, this setup allows for completely force-field-based simulations of
      photochemical cis->trans- and trans->cis-isomerizations of azobenzene, with
      qualitatively acceptable quantum yields. This paves the way towards large-scale
      dynamics simulations of molecular machines, including bond breaking and formation
      (via the reactive force field) as well as photochemical engines (presented in
      this work). 

PMID- 24329066
TI  - Ionic liquids from the bottom up: local assembly motifs in [EMIM][BF4] through
      cryogenic ion spectroscopy.
AB  - To clarify the intramolecular distortions exhibited by the complementary ions in
      the archetypal ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate
      [EMIM][BF4], we report the vibrational spectra of the isolated ionic constituents
      and small aggregates cooled to about 10 K. Deuteration of bare EMIM(+) at the
      C(2) position, the putative hydrogen bond donating group, establishes that the
      observed bulk red shift is too small (<10 cm(-1)) for hydrogen bonding to be a
      dominant structural feature. We then analyze how the vibrational patterns evolve
      with increasing size to identify the spectral signatures of well-defined
      structural motifs in the growing assembly. Surprisingly, the main features of the
      bulk spectrum are already developed in the cluster with a single BF4 (-) anion
      sandwiched between just two EMIM(+) cations. We suggest that this local motif,
      while not strongly hydrogen bonded, nonetheless induces considerable intensity in
      the C(2)H stretches and is a robust feature in the local molecular structure of
      the liquid. 

PMID- 24329065
TI  - Rotational spectroscopy of pyridazine and its isotopologs from 235-360 GHz:
      equilibrium structure and vibrational satellites.
AB  - The rotational spectrum of pyridazine (o-C4H4N2), the ortho disubstituted
      nitrogen analog of benzene, has been measured and analyzed in the gas phase. For
      the ground vibrational state of the normal isotopolog, over 2000 individual
      rotational transitions have been identified between 238 and 360 GHz and have been
      fit to 13 parameters of a 6th-order centrifugal distortion Hamiltonian. All
      transitions in this frequency region can now be predicted from this model to near
      experimental accuracy, i.e., well enough for the purpose of any future radio
      astronomical search for this species. Three isotopologs, [3-(13)C]-C4H4N2, [4
      (13)C]-C4H4N2, and [1-(15)N]-C4H4N2, have been detected in natural abundance, and
      several hundred lines have been measured for each of these species and fit to 6th
      order Hamiltonians. Ten additional isotopologs were synthesized with enhanced
      deuterium substitution and analyzed to allow for a complete structure
      determination. The equilibrium structure (Re) of pyridazine was obtained by
      correcting the experimental rotational constants for the effects of vibration
      rotation coupling using interaction constants predicted from CCSD(T) calculations
      with an ANO0 basis set and further correcting for the effect of electron mass.
      The final Re structural parameters are determined with excellent accuracy, as
      evidenced by their ability to predict 28 independent moments of inertia (Ia and
      Ib for 14 isotopologs) very well from 9 structural parameters. The rotational
      spectra of the six lowest-energy fundamental vibrational satellites of the main
      isotopolog have been detected. The rotational spectra of the five lowest-energy
      vibrational satellites have been assigned and fit to yield accurate rotational
      and distortion constants, while the fit and assignment for the sixth is less
      complete. The resultant vibration-rotation interaction (alpha) constants are
      found to be in excellent agreement with ones predicted from coupled-cluster
      calculations, which proved to be the key to unambiguous assignment of the
      satellite spectra to specific vibration modes. 

PMID- 24329067
TI  - The stability of S-states of unit-charge Coulomb three-body systems: from H- to
      H2(+).
AB  - High accuracy non-relativistic quantum chemical calculations of the ground state
      energies and wavefunctions of symmetric three-particle Coulomb systems of the
      form {m1(+/-)m2(+/-)m3(?)}, m1 = m2, are calculated using an efficient and
      effective series solution method in a triple orthogonal Laguerre basis set. These
      energies are used to determine an accurate lower bound to the stability zone of
      unit-charge three-particle Coulomb systems using an expression for the width of
      the stability band in terms of g, the fractional additional binding due to a
      third particle. The results are presented in the form of a reciprocal mass
      fraction ternary diagram and the energies used to derive a parameterised function
      g(a3), where a3=m3 (-1)/(m1(-1)+m2(-1)+m3(-1)) is the reciprocal mass of the
      uniquely charged particle. It is found that the function is not minimal at a3 = 0
      which corresponds to infinityH(-) nor is it minimal at the positronium negative
      ion (Ps(-)) the system with the least absolute energetic gain by association with
      a third particle; the function g(a3) is minimal at m1/m3 = 0.49, and a possible
      physical interpretation in terms of the transition from atomic-like to molecular
      like is provided.

PMID- 24329068
TI  - Three-chain B(6n+14) cages as possible precursors for the syntheses of boron
      fullerenes.
AB  - Using the first principle methods, we proposed a series of three-chain boron
      cages B6n+14 (n = 1-12) which are mainly built by fusing three boron semi-double
      rings. Their simple geometric structures (approximate D3 or C3 symmetry)
      facilitate their bottom-up syntheses from the hexagonal B7 and the double-chain
      boron clusters, such as B2, B4, B6, B8H2, B10H2, B12H2, and the double ring B20.
      The spherical shapes of these three-chain boron cages show that they could be
      taken as the possible precursors to further synthesize the boron fullerenes, such
      as B80. Therefore, these three-chain boron cages provide a possible synthesis
      pathway of the boron fullerenes from the experimentally synthesized small planar
      boron clusters. 

PMID- 24329069
TI  - Combined photoelectron, collision-induced dissociation, and computational studies
      of parent and fragment anions of N-paranitrophenylsulfonylalanine and N
      paranitrophenylalanine.
AB  - After synthesizing the compounds N-paranitrophenylsulfonylalanine (NPNPSA) and N
      paranitrophenylalanine (NPNPA), the photoelectron spectrum of the valence anion
      of N-paranitrophenylsulfonylalanine (NPNPSA)(-), was measured and the collision
      induced dissociation (CID) pathways of deprotonated N
      paranitrophenylsulfonylalanine (NPNPSA-H)(-) and deprotonated N
      paranitrophenylalanine (NPNPA-H)(-) were determined. Pertinent calculations were
      conducted to analyze both sets of experimental data. From the valence anion
      photoelectron spectrum of (NPNPSA)(-), the adiabatic electron affinity (AEA) of
      NPNPSA was determined to be 1.7 +/- 0.1 eV, while the vertical detachment energy
      (VDE) of (NPNPSA)(-) was found to be 2.3 +/- 0.1 eV. Calculations for four low
      lying conformers of (NPNPSA)(-) gave AEA values in the range of 1.6-2.1 eV and
      VDE values in the range of 2.0-2.4 eV. These calculations are in very good
      agreement with the experimental values. While the NPNPA anion (NPNPSA)(-) was not
      observed experimentally it was studied computationally. The six low lying
      (NPNPSA)(-) conformers were identified and calculated to have AEA values in the
      range of 0.7-1.2 eV and VDE values in the range of 0.9-1.6 eV. CID was used to
      study the fragmentation patterns of deprotonated NPNPA and deprotonated NPNPSA.
      Based on the CID data and calculations, the excess charge was located on the
      delocalized pi-orbitals of the nitrobenzene moiety. This is made evident by the
      fact that the dominant fragments all contained the nitrobenzene moiety even
      though the parent anions used for the CID study were formed via deprotonation of
      the carboxylic acid. The dipole-bound anions of both molecules are studied
      theoretically using the results of previous studies on nitrobenzene as a
      reference. 

PMID- 24329070
TI  - On the origin of high transient anisotropies: an exemplification in a Cd
      porphyrin.
AB  - Transient anisotropy is a widely used spectroscopic method to access the
      polarization dynamics of a molecular sample. In this contribution, we present
      results on 5,10,15,20-tetraphenyl-porphyrinato cadmium (II) in tetrahydrofuran
      which exhibits values exceeding the typical range between 0.4 and -0.2 in
      dependence of the probe wavelength. These findings are explained by varying
      contributions from excited state absorption and ground state bleaching/stimulated
      emission. Model calculations show that time zero values and time decays are
      complex values that often do not correlate with the underlying physical
      processes. As a consequence, the interpretation of anisotropy experiments
      necessitates extreme care. 

PMID- 24329071
TI  - Competition between abstraction and exchange channels in H + HCN reaction: full
      dimensional quantum dynamics.
AB  - Dynamics of the title reaction is investigated on an ab initio based potential
      energy surface using a full-dimensional quantum wave packet method within the
      centrifugal sudden approximation. It is shown that the reaction between H and HCN
      leads to both the hydrogen exchange and hydrogen abstraction channels. The
      exchange channel has a lower threshold and larger cross section than the
      abstraction channel. It also has more oscillations due apparently to quantum
      resonances. Both channels are affected by long-lived resonances supported by
      potential wells. Comparison with experimental cross sections indicates
      underestimation of the abstraction barrier height. 

PMID- 24329072
TI  - Critical anomalies of alkaline fading of phenolphthalein in the critical solution
      of 2-butoxyethanol + water.
AB  - We have used three-wavelength UV-spectrophotometry to study the reaction of the
      alkaline fading of phenolphthalein in the critical solution of 2-butoxyethanol +
      water. It was found that when the temperature was far away from the critical
      point, the values of the natural logarithm of the rate constant k and the natural
      logarithm of the chemical equilibrium K determined in our experiments had good
      linear relationships with the reciprocal of temperature, which served as the
      backgrounds and were used for correcting k and K in the critical region. The
      critical slowing down of the reaction and the critical anomaly of the chemical
      equilibrium were detected near the critical point. The value of the critical
      exponent characterizing the slowing down effect of the reaction rate was obtained
      to be 0.156, which was close to the value 0.11 associated with the heat capacity
      divergence and agreed with the theoretical prediction. The experimental result
      also confirmed the theoretical prediction of 0.11 for the critical exponent
      characterizing the weak divergence of the singularity of the chemical
      equilibrium. 

PMID- 24329073
TI  - Insights on cholinium- and piperazinium-based ionic liquids under external
      electric fields: a molecular dynamics study.
AB  - The rotational and translational response of cholinium benzoate, cholinium
      salicylate, piperazinium benzoate, and piperazinium salicylate to static and
      dynamic external electric fields was studied using non-equilibrium molecular
      dynamics simulations. The existence of strong intrinsic electric fields in the
      studied fluids requires intensities larger than 0.25 V A(-1) to obtain remarkable
      changes in the fluids' properties, such as rotational motion, dipolar alignment,
      or ion diffusivities. Very effective dipolar alignment with the applied fields is
      obtained showing rotational motions in the direction of the applied field,
      increasing with field intensity and decreasing with field frequency.
      Translational movement is clearly improved by the applied fields specially for
      strong fields and low frequencies, which lead to ionic diffusivities increasing
      up to two orders of magnitude for the stronger fields in comparison with zero
      field situations, and thus, increasing remarkably fluids' electrical
      conductivity. The effect of external electric fields on the studied ionic liquids
      is weaker than in common imidazolium-based ionic liquids. 

PMID- 24329074
TI  - Regimes of streaming potential in cylindrical nano-pores in presence of finite
      sized ions and charge induced thickening: an analytical approach.
AB  - We obtain approximate analytical expressions for the streaming potential and the
      effective viscosity in a pure pressure-driven flow through a cylindrical pore
      with electrokinetic interactions, duly accounting for the finite size effects of
      the ionic species (steric effects) and charge-induced thickening. Our analytical
      results show a remarkable agreement with the numerical solution even for high
      surface potentials and small channel radii. We demonstrate a consistent increment
      in the predicted value of the streaming potential and effective viscosity when
      finite size effects of the ionic species are accounted for. In addition to this,
      we account for the radial variation of in the viscosity of the fluid due to
      charge-induced thickening. We show that this so-called viscoelectric effect leads
      to a decrease in the induced streaming potential especially at high steric
      factors and high surface potentials. However, the viscoelectric effect, which is
      prominent at high zeta potential and narrow channels, does not cause significant
      changes in the electrokinetic conversion efficiency. These results shed light on
      the interesting confluence of the steric factor, the channel radius, the
      electrical double layer screening length, and the surface charge density in
      conjunction with the charge induced thickening, and thus provide ion-size
      dependent analytical framework for accurate system design and better
      interpretation of electrokinetic data. 

PMID- 24329075
TI  - Revisiting dynamics near a liquid-liquid phase transition in Si and Ga: the
      fragile-to-strong transition.
AB  - Using molecular dynamics simulations we analyze the dynamics of two atomic
      liquids that display a liquid-liquid phase transition (LLPT): Si described by the
      Stillinger-Weber potential and Ga as modeled by the modified embedded-atom model.
      In particular, our objective is to investigate the extent to which the presence
      of a dip in the self-intermediate scattering function is a manifestation of an
      excess of vibrational states at low frequencies and may be associated with a
      fragile-to-strong transition (FTST) across the LLPT, as suggested recently. Our
      results suggest a somewhat different picture. First, in the case of Ga we observe
      the appearance of an excess of vibrational states at low frequencies, even in the
      absence of the appearance of a dip in the self-intermediate scattering function
      across the LLPT. Second, studying the behavior of the shear viscosities
      traversing the LLPTs we find that both substances are fragile in character above
      and below their respective LLPT temperatures. Instead of a FTST in an absolute
      sense these findings are more in line with a view in which the LLPTs are
      accompanied by a transition from a more fragile to a less fragile liquid.
      Furthermore, we do not find this transition to correlate with the presence of a
      dip in the intermediate scattering function. 

PMID- 24329076
TI  - Surface structures of binary mixtures of imidazolium-based ionic liquids using
      high-resolution Rutherford backscattering spectroscopy and time of flight
      secondary ion mass spectroscopy.
AB  - Surface structures of binary mixtures of imidazolium-based ionic liquids having a
      common anion (bis(trifluoromethanesulfonyl)imide ([TFSI]), namely [C2MIM]1
      x[C10MIM]x[TFSI] (x = 0.5 and 0.1), are studied using high-resolution Rutherford
      backscattering spectroscopy (HRBS) and time of flight secondary ion mass
      spectroscopy (TOF-SIMS). Although both measurements show surface segregation of
      [C10MIM] the degrees of the segregation are different. The surface fraction xsurf
      of [C10MIM] is estimated to be 0.6 +/- 0.05 and 0.18 +/- 0.02 by HRBS for x = 0.5
      and 0.1, respectively. On the other hand, TOF-SIMS indicates much stronger
      surface segregation, namely xsurf = 0.83 +/- 0.03 and 0.42 +/- 0.04 for x = 0.5
      and 0.1, respectively. The observed discrepancy can be attributed to the
      difference in the probing depth between HRBS and TOF-SIMS. The observed surface
      segregation can be roughly explained in terms of surface tension.

PMID- 24329077
TI  - Strain effect on the adsorption, diffusion, and molecular dissociation of
      hydrogen on Mg (0001) surface.
AB  - The adsorption, diffusion, and molecular dissociation of hydrogen on the
      biaxially strained Mg (0001) surface have been systematically investigated by the
      first principle calculations based on density functional theory. When the strain
      changes from the compressive to tensile state, the adsorption energy of H atom
      linearly increases while its diffusion barrier linearly decreases oppositely. The
      dissociation barrier of H2 molecule linearly reduces in the tensile strain
      region. Through the chemical bonding analysis including the charge density
      difference, the projected density of states and the Mulliken population, the
      mechanism of the strain effect on the adsorption of H atom and the dissociation
      of H2 molecule has been elucidated by an s-p charge transfer model. With the
      reduction of the orbital overlap between the surface Mg atoms upon the lattice
      expansion, the charge transfers from p to s states of Mg atoms, which enhances
      the hybridization of H s and Mg s orbitals. Therefore, the bonding interaction of
      H with Mg surface is strengthened and then the atomic diffusion and molecular
      dissociation barriers of hydrogen decrease accordingly. Our works will be helpful
      to understand and to estimate the influence of the lattice deformation on the
      performance of Mg-containing hydrogen storage materials. 

PMID- 24329078
TI  - Temperature dependence of the crystal-liquid interfacial free energy and the
      endpoint of the melting line.
AB  - The crystal-liquid interfacial free energy gamma has been calculated as a
      function of the crystal orientation in a molecular dynamics experiment in a
      system of Lennard-Jones (LJ) particles with a cutoff radius of the potential
      rc(*)=rc/sigma=6.78 at a triple-point temperature Tt(*)=kBTt/epsilon=0.692 and
      temperatures above (in the region of the stable coexistence of liquid and solid
      phases) and below (metastable continuation of the coexistence curve of liquid and
      solid phases) the temperature Tt(*). At T(*)=Tt(*), for determining gamma use was
      made of the method of cleaving potential. The temperature dependence of gamma on
      the crystal-liquid coexistence curve has been determined by the Gibbs-Cahn
      thermodynamic integration method. In the region of stable phase coexistence
      (T(*)>Tt(*)) good agreement with the data of Davidchack and Laird [J. Chem. Phys.
      118, 7651 (2003)] has been obtained with respect to the character of the
      temperature dependence of gamma and the orientation anisotropy. In the region of
      metastable phase coexistence (T(*)<Tt(*)) at the approach to the endpoint of the
      melting line (TK(*)=0.529) (the existence of which was established first by
      Baidakov and Protsenko [Phys. Rev. Lett. 95, 015701 (2005)]) the interfacial free
      energy decreases, approaching at T(*)=TK(*) the orientation-averaged value
      gamma0K(*)=gamma0Ksigma(2/epsilon)=0.365. The paper discusses the behavior of the
      excess interfacial energy, excess interfacial entropy and excess interfacial
      stress on the metastable extension of the melting line and close to T(*)=TK(*).

PMID- 24329079
TI  - Binding and interlayer force in the near-contact region of two graphite slabs:
      experiment and theory.
AB  - Via a novel experiment, Liu et al. [Phys. Rev. B 85, 205418 (2012)] estimated the
      graphite binding energy, specifically the cleavage energy, an important physical
      property of bulk graphite. We re-examine the data analysis and note that within
      the standard Lennard-Jones model employed, there are difficulties in achieving
      internal consistency in the reproduction of the graphite elastic properties. By
      employing similar models which guarantee consistency with the elastic constant,
      we find a wide range of model dependent binding energy values from the same
      experimental data. We attribute some of the difficulties in the determination of
      the binding energy to: (i) limited theoretical understanding of the van der Waals
      dispersion of graphite cleavage, (ii) the mis-match between the strong bending
      stiffness of the graphite-SiO2 cantilever and the weak asymptotic inter-layer
      forces that are integrated over to produce the binding energy. We find, however,
      that the data do support determination of a maximum inter-layer force that is
      relatively model independent. We conclude that the peak force per unit area is
      1.1 +/- 0.15 GPa for cleavage, and occurs at an inter-layer spacing of 0.377 +/-
      0.013 nm. 

PMID- 24329080
TI  - A first-principles study of structural and elastic properties of bulk SrRuO3.
AB  - We present a first-principles investigation of structural and elastic properties
      of experimentally observed phases of bulk SrRuO3 - namely orthorhombic,
      tetragonal, and cubic - by applying density functional theory (DFT)
      approximations. First, we focus our attention on the accuracy of calculated
      lattice constants in order to find out DFT approaches that best represent the
      crystalline structure of SrRuO3, since many important physical quantities
      crucially depend on change in volume. Next, we evaluate single-crystal elastic
      constants, macroscopic elastic parameters, and mechanical stability trying to at
      least partially compensate for the existing lack of information about these
      fundamental features of SrRuO3. Finally, we analyze the anomalous behavior of low
      temperature orthorhombic phase under C44 related shear deformation. It turns out
      that at critical strain values the system exhibits a distinct deviation from the
      initial behavior which results in an isosymmetric phase transition. Moreover,
      under C44 related shear deformation tetragonal SrRuO3 becomes mechanically
      unstable raising an open question of what makes it experimentally observable at
      high temperatures. 

PMID- 24329081
TI  - Parallel kinetic Monte Carlo simulation framework incorporating accurate models
      of adsorbate lateral interactions.
AB  - Ab initio kinetic Monte Carlo (KMC) simulations have been successfully applied
      for over two decades to elucidate the underlying physico-chemical phenomena on
      the surfaces of heterogeneous catalysts. These simulations necessitate detailed
      knowledge of the kinetics of elementary reactions constituting the reaction
      mechanism, and the energetics of the species participating in the chemistry. The
      information about the energetics is encoded in the formation energies of gas and
      surface-bound species, and the lateral interactions between adsorbates on the
      catalytic surface, which can be modeled at different levels of detail. The
      majority of previous works accounted for only pairwise-additive first nearest
      neighbor interactions. More recently, cluster-expansion Hamiltonians
      incorporating long-range interactions and many-body terms have been used for
      detailed estimations of catalytic rate [C. Wu, D. J. Schmidt, C. Wolverton, and
      W. F. Schneider, J. Catal. 286, 88 (2012)]. In view of the increasing interest in
      accurate predictions of catalytic performance, there is a need for general
      purpose KMC approaches incorporating detailed cluster expansion models for the
      adlayer energetics. We have addressed this need by building on the previously
      introduced graph-theoretical KMC framework, and we have developed Zacros, a
      FORTRAN2003 KMC package for simulating catalytic chemistries. To tackle the high
      computational cost in the presence of long-range interactions we introduce
      parallelization with OpenMP. We further benchmark our framework by simulating a
      KMC analogue of the NO oxidation system established by Schneider and co-workers
      [J. Catal. 286, 88 (2012)]. We show that taking into account only first nearest
      neighbor interactions may lead to large errors in the prediction of the catalytic
      rate, whereas for accurate estimates thereof, one needs to include long-range
      terms in the cluster expansion. 

PMID- 24329082
TI  - High-resolution neutron diffraction study of CuNCN: new evidence of structure
      anomalies at low temperature.
AB  - Copper carbodiimide (CuNCN) is the nitrogen-containing analogue of cupric oxide.
      Based on high-resolution neutron-diffraction data, CuNCN's lattice parameters are
      derived as a function of the temperature. In accordance with a recent synchrotron
      study, a clear trend in the cell parameter a is observed accompanying the
      changing magnetic behavior. With decreasing temperature, a slowly decreases to a
      minimum at ~100 K after which it rises again. The same trend-albeit more
      pronounced-is observed for the c lattice parameter at ~35 K. The herein presented
      neutron powder-diffraction data also support the conjectured sequence of
      transitions from the high-temperature one-dimensional resonating valence-bond
      (RVB) state to a transient two-dimensional RVB state and eventually, at lowest
      temperatures, into another two-dimensional RVB state, presumably the ground
      state.

PMID- 24329083
TI  - Spin-polarized hydrogen adsorbed on the surface of superfluid 4He.
AB  - The experimental realization of a thin layer of spin-polarized hydrogen H?
      adsorbed on top of the surface of superfluid (4)He provides one of the best
      examples of a stable, nearly two-dimensional (2D) quantum Bose gas. We report a
      theoretical study of this system using quantum Monte Carlo methods in the limit
      of zero temperature. Using the full Hamiltonian of the system, composed of a
      superfluid (4)He slab and the adsorbed H? layer, we calculate the main properties
      of its ground state using accurate models for the pair interatomic potentials.
      Comparing the results for the layer with the ones obtained for a strictly 2D
      setup, we analyze the departure from the 2D character when the density increases.
      Only when the coverage is rather small the use of a purely 2D model is justified.
      The condensate fraction of the layer is significantly larger than in 2D at the
      same surface density, being as large as 60% at the largest coverage studied. 

PMID- 24329084
TI  - Enantioselectivity of (321) chiral noble metal surfaces: a density functional
      theory study of lactate adsorption.
AB  - The adsorption of the chiral molecule lactate on the intrinsically chiral noble
      metal surfaces Pt(321), Au(321), and Ag(321) is studied by density functional
      theory calculations. We use the oPBE-vdW functional which includes van der Waals
      forces on an ab initio level. It is shown that the molecule binds via its
      carboxyl and the hydroxyl oxygen atoms to the surface. The binding energy is
      larger on Pt(321) and Ag(321) than on Au(321). An analysis of the contributions
      to the binding energy of the different molecular functional groups reveals that
      the deprotonated carboxyl group contributes most to the binding energy, with a
      much smaller contribution of the hydroxyl group. The Pt(321) surface shows
      considerable enantioselectivity of 0.06 eV. On Au(321) and Ag(321) it is much
      smaller if not vanishing. The chiral selectivity of the Pt(321) surface can be
      explained by two factors. First, it derives from the difference in van der Waals
      attraction of L- and D-lactate to the surface that we trace to differences in the
      binding energy of the methyl group. Second, the multi-point binding pattern for
      lactate on the Pt(321) surface is sterically more sensitive to surface chirality
      and also leads to large binding energy contributions of the hydroxyl group. We
      also calculate the charge transfer to the molecule and the work function to gauge
      changes in electronic structure of the adsorbed molecule. The work function is
      lowered by 0.8 eV on Pt(321) with much smaller changes on Au(321) and Ag(321).

PMID- 24329085
TI  - The relationship between local liquid density and force applied on a tip of
      atomic force microscope: a theoretical analysis for simple liquids.
AB  - The density of a liquid is not uniform when placed on a solid. The structured
      liquid pushes or pulls a probe employed in atomic force microscopy, as
      demonstrated in a number of experimental studies. In the present study, the
      relation between the force on a probe and the local density of a liquid is
      derived based on the statistical mechanics of simple liquids. When the probe is
      identical to a solvent molecule, the strength of the force is shown to be
      proportional to the vertical gradient of ln(rhoDS) with the local liquid's
      density on a solid surface being rhoDS. The intrinsic liquid's density on a solid
      is numerically calculated and compared with the density reconstructed from the
      force on a probe that is identical or not identical to the solvent molecule. 

PMID- 24329086
TI  - Fluid of Janus molecules between two walls: the solvation force.
AB  - We apply a density functional theory to calculate the solvation force in the
      system involving Janus particles confined between two planar walls. Janus
      particles are modeled as spheres composed of attractive and repulsive parts and
      their orientation is described by the vectors representing internal degrees of
      freedom. We consider the cases of pores with identical walls, as well as the
      pores with competing walls (the so-called Janus-like pores). The density
      functional approach we employ combines fundamental measure theory with a mean
      field approximation for the anisotropic interparticle interaction. We study how
      the solvation force and the orientational structure of confined particles depend
      on the competition between the surface field and the interactions between
      confined molecules and on the parameters of the model such as temperature and
      density. It is shown that the anisotropic interaction between the confined
      molecules and the character of the walls significantly influence the solvation
      force. 

PMID- 24329087
TI  - Phase diagrams of block copolymer melts by dissipative particle dynamics
      simulations.
AB  - Phase diagrams for monodisperse and polydisperse diblock copolymer melts and a
      random multiblock copolymer melt are constructed using dissipative particle
      dynamics simulations. A thorough visual analysis and calculation of the static
      structure factor in several hundreds of points at each of the diagrams prove the
      ability of mesoscopic molecular dynamics to predict the phase behavior of polymer
      systems as effectively as the self-consistent field-theory and Monte Carlo
      simulations do. It is demonstrated that the order-disorder transition (ODT) curve
      for monodisperse diblocks can be precisely located by a spike in the dependence
      of the mean square pressure fluctuation on chiN, where chi is the Flory-Huggins
      parameter and N is the chain length. For two other copolymer types, the
      continuous ODTs are observed. Large polydispersity of both blocks obeying the
      Flory distribution in length does not shift the ODT curve but considerably
      narrows the domains of the cylindrical and lamellar phases partially replacing
      them with the wormlike micelle and perforated lamellar phases, respectively.
      Instead of the pure 3d-bicontinuous phase in monodisperse diblocks, which could
      be identified as the gyroid, a coexistence of the 3d phase and cylindrical
      micelles is detected in polydisperse diblocks. The lamellar domain spacing D in
      monodisperse diblocks follows the strong-segregation theory prediction, D/N(1/2)
      ~ (chiN)(1/6), whereas in polydisperse diblocks it is almost independent of chiN
      at chiN < 100. Completely random multiblock copolymers cannot form ordered
      microstructures other than lamellas at any composition.

PMID- 24329088
TI  - Dynamics of a polyelectrolyte in simple shear flow.
AB  - The configurational dynamics of a polyelectrolyte (PE), subjected to a simple
      shear flow, is studied using Brownian dynamics (BD) and Dissipative Particle
      Dynamics (DPD) simulations of a bead-spring model with explicit counterions. We
      explore the effect of counterion condensation on the tumbling and extension of
      PEs by varying the shear rates for a range of values of the electrostatic
      coupling parameter A (which is defined as the ratio of the Bjerrum length to the
      size of the monomer). In all cases, the power spectrum of Rs(t) (which
      characterizes the projected length of the PE in the flow direction as a function
      of time) exhibits a power law decay at high frequencies, similar to that for a
      dumbbell in shear flow. For lower values of A (A ~ 2), the tumbling of the PE is
      periodic and is always associated with folding and stretching, which is in
      contrast to the oscillatory transition between the extended and globular states
      seen at higher values of A (A ~ 15). We observe that for A ~ 2 the tumbling
      frequency decreases and the average tumbling time increases with hydrodynamic
      interaction (HI). For A > 15, we observe a critical shear rate gamma[combining
      dot]c below which there is considerable counterion condensation and the PE
      remains in the globular state with a structure akin to that of a neutral polymer
      in poor solvent. The gamma[combining dot]c and the behavior of the PE above the
      critical shear rate are dependent on the HI. For a given shear rate, when there
      is considerable condensed counterion fluctuation, the PE extends as a whole and
      then collapses by the formation of folds with no observable periodicity in
      tumbling. When the condensed counterion fluctuations are suppressed, the polymer
      exhibits periodic tumbling. Simulation artifacts resulting from the implicit
      nature of the solvent and that due to boundary conditions are discussed by
      comparing the BD results with that obtained from the DPD simulations
      incorporating Ewald summation for electrostatics.

PMID- 24329089
TI  - Some aspects of the orientational order distribution of flexible chains in a
      diblock mesophase.
AB  - The segmental motions of flexible chains in the lamellar structure of a strongly
      segregated poly(styrene)-poly(dimethylsiloxane) (PS-PDMS) diblock were
      investigated over a time scale of a few tens of microseconds. (2)H NMR
      experiments were performed on the PDMS block, selectively perdeuterated.
      Transverse relaxation measurements show that the main part of the PDMS repeat
      units display anisotropic reorientational motions within the diblock lamellae and
      such a segmental ordering essentially results from interchain steric repulsions.
      (2)H double quantum-based experiments evidenced a non-uniform local stretching of
      PDMS chains and enabled the underlying distribution of the orientational order
      parameter to be determined quantitatively. Besides, a fraction of the PDMS chain
      segments, about 14%, were found to display isotropic - or nearly isotropic -
      reorientations, which could be assigned to repeat units located within a thin
      sublayer (about 1-2 nm) at the lamellae midplane, but also deeper in the
      lamellae, close to folded parts of the chains. These experimental results were
      confronted to theoretical descriptions of opposing polymer brushes and, in
      particular, to the strong-stretching theory (SST) including the entropic
      contribution of free chain ends. 

PMID- 24329090
TI  - A percolation-based model for the conductivity of nanofiber composites.
AB  - A model is presented that integrates the critical path approximation with
      percolation theory to describe the dependence of electrical conductivity upon
      volume fraction in nanofiber-based composites. The theory accounts for clustering
      and correlation effects that reflect non-randomness in the spatial distribution
      of the particles. Results from this formalism are compared to experimental
      measurements performed upon carbon nanotube-based conductive nanocomposites. 

PMID- 24329091
TI  - Structure factor of model bidisperse ferrofluids with relatively weak
      interparticle interactions.
AB  - In the present manuscript we develop a theoretical approach to describe the pair
      correlation function of bidisperse magnetic dipolar hard- and soft-spheres. We
      choose bidisperse system as the first step to allow for polydispersity when
      studying thermodynamics of magnetic fluids. Using diagram technique we calculate
      the virial expansion of the pair correlation function up to the first order in
      density and fourth order in the dipolar strength. Even though, the radial
      distribution functions are extremely sensitive to the steric potential, we show
      that the behaviour of the isotropic centre-centre structure factor is almost
      indifferent to the type of the short-range repulsion. We extensively compare our
      theoretical results to the data of molecular dynamics simulations, which helps us
      to understand the range of validity of the virial expansion both on density and
      magnetic dipolar strength. We also investigate the influence of the granulometric
      composition on the height, width, and position of the structure factor first peak
      in order to clarify whether it is possible to extract structural information from
      experimentally measured small angle neutron scattering intensities. 

PMID- 24329092
TI  - The entropy of the rotational conformations of (poly)isoprene molecules and its
      relationship to rubber elasticity and temperature increase for moderate tensile
      or compressive strains.
AB  - Molecular networks comprised of crosslinked cis-1,4 polyisoprene, often referred
      to as "natural rubber," are one of the most common systems for the study of
      rubber elasticity. Under moderate tensile or compressive strain, network chains
      begin to assume straighter paths, as local molecular kinks are removed. Isoprene
      units along the chain backbone are mechanically forced from their equilibrium
      distributions of 18 possible rotational states into a smaller subset of states,
      restricted to more linear conformations with the greatest end-to-end distances.
      There are two consequences to this change: both the configurational entropy and
      average internal energy decrease. We find that the change in entropy, and
      resulting change in free energy, gives rise to an elastic force. We derive an
      expression for a chain extension force constant that we have incorporated in an
      explicit, three-dimensional meso-scale network simulation code. Using this force
      model, our simulations predict a macroscopic stress-strain relationship that
      closely matches published experimental values. We also predict a slight increase
      in temperature resulting from the change in average internal energy in the
      affected isoprene units that is consistent with experiments. 

PMID- 24329093
TI  - Volume properties and spectroscopy: a terahertz Raman investigation of hen egg
      white lysozyme.
AB  - The low frequency depolarized Raman spectra of 100 mg/ml aqueous solutions of hen
      egg white lysozyme (HEWL) have been collected in the 25-85  degrees C range.
      Short and long exposures to high temperatures have been used to modulate the
      competition between the thermally induced reversible and irreversible
      denaturation processes. A peculiar temperature evolution of spectra is evidenced
      under prolonged exposure of the protein solution at temperatures higher than 65 
      degrees C. This result is connected to the self-assembling of polypeptide chains
      and testifies the sensitivity of the technique to the properties of both protein
      molecule and its surrounding. Solvent free spectra have been obtained after
      subtraction of elastic and solvent components and assigned to a genuine
      vibrational contribution of hydrated HEWL. A straight similarity is observed
      between the solvent-free THz Raman feature and the vibrational density of states
      as obtained by molecular dynamics simulations; according to this, we verify the
      relation between this spectroscopic observable and the effective protein volume,
      and distinguish the properties of this latter respect to those of the hydration
      shell in the pre-melting region.

PMID- 24329094
TI  - Molecular insight into conformational transmission of human P-glycoprotein.
AB  - P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export
      candidates through a channel at the two transmembrane domains (TMDs) across the
      cell membranes using the energy released from ATP hydrolysis at the two
      nucleotide-binding domains (NBDs). Considerable evidence has indicated that human
      P-gp undergoes large-scale conformational changes to export a wide variety of
      anti-cancer drugs out of the cancer cells. However, molecular mechanism of the
      conformational transmission of human P-gp from the NBDs to the TMDs is still
      unclear. Herein, targeted molecular dynamics simulations were performed to
      explore the atomic detail of the conformational transmission of human P-gp. It is
      confirmed that the conformational transition from the inward- to outward-facing
      is initiated by the movement of the NBDs. It is found that the two NBDs move both
      on the two directions (x and y). The movement on the x direction leads to the
      closure of the NBDs, while the movement on the y direction adjusts the
      conformations of the NBDs to form the correct ATP binding pockets. Six key
      segments (KSs) protruding from the TMDs to interact with the NBDs are identified.
      The relative movement of the KSs along the y axis driven by the NBDs can be
      transmitted through alpha-helices to the rest of the TMDs, rendering the TMDs to
      open towards periplasm in the outward-facing conformation. Twenty eight key
      residue pairs are identified to participate in the interaction network that
      contributes to the conformational transmission from the NBDs to the TMDs of human
      P-gp. In addition, 9 key residues in each NBD are also identified. The studies
      have thus provided clear insight into the conformational transmission from the
      NBDs to the TMDs in human P-gp. 

PMID- 24329095
TI  - Structural flexibility of intrinsically disordered proteins induces stepwise
      target recognition.
AB  - An intrinsically disordered protein (IDP) lacks a stable three-dimensional
      structure, while it folds into a specific structure when it binds to a target
      molecule. In some IDP-target complexes, not all target binding surfaces are
      exposed on the outside, and intermediate states are observed in their binding
      processes. We consider that stepwise target recognition via intermediate states
      is a characteristic of IDP binding to targets with "hidden" binding sites. To
      investigate IDP binding to hidden target binding sites, we constructed an IDP
      lattice model based on the HP model. In our model, the IDP is modeled as a chain
      and the target is modeled as a highly coarse-grained object. We introduced motion
      and internal interactions to the target to hide its binding sites. In the case of
      unhidden binding sites, a two-state transition between the free states and a
      bound state is observed, and we consider that this represents coupled folding and
      binding. Introducing hidden binding sites, we found an intermediate bound state
      in which the IDP forms various structures to temporarily stabilize the complex.
      The intermediate state provides a scaffold for the IDP to access the hidden
      binding site. We call this process multiform binding. We conclude that structural
      flexibility of IDPs enables them to access hidden binding sites and this is a
      functional advantage of IDPs. 

PMID- 24329096
TI  - The eigenmode perspective of NMR spin relaxation in proteins.
AB  - We developed in recent years the two-body (protein and probe) coupled-rotator
      slowly relaxing local structure (SRLS) approach for elucidating protein dynamics
      from NMR spin relaxation. So far we used as descriptors the set of physical
      parameters that enter the SRLS model. They include the global (protein-related)
      diffusion tensor, D1, the local (probe-related) diffusion tensor, D2, and the
      local coupling/ordering potential, u. As common in analyzes based on mesoscopic
      dynamic models, these parameters have been determined with data-fitting
      techniques. In this study, we describe structural dynamics in terms of the
      eigenmodes comprising the SRLS time correlation functions (TCFs) generated by
      using the best-fit parameters as input to the Smoluchowski equation. An eigenmode
      is a weighted exponential with decay constant given by an eigenvalue of the
      Smoluchowski operator, and weighting factor determined by the corresponding
      eigenvector. Obviously, both quantities depend on the SRLS parameters as
      determined by the SRLS model. Unlike the set of best-fit parameters, the
      eigenmodes represent patterns of motion of the probe-protein system. The
      following new information is obtained for the typical probe, the (15)N-(1)H bond.
      Two eigenmodes, associated with the protein and the probe, dominate when the time
      scale separation is large (i.e., D2 >> D1), the tensorial properties are simple,
      and the local potential is either very strong or very weak. When the potential
      exceeds these limits while the remaining conditions are preserved, new eigenmodes
      arise. The multi-exponentiality of the TCFs is associated in this case with the
      restricted nature of the local motion. When the time scale separation is no
      longer large, the rotational degrees of freedom of the protein and the probe
      become statistically dependent (coupled dynamically). The multi-exponentiality of
      the TCFs is associated in this case with the restricted nature of both the local
      and the global motion. The effects of local diffusion axiality, potential
      strength, and extent of mode-coupling on the eigenmode setup are investigated. We
      detect largely global motional or largely local motional eigenmodes. In addition,
      we detect mixed eigenmodes associated with correlated/prograde or anti
      correlated/retrograde rotations of the global (D1) and local (D2) motional modes.
      The eigenmode paradigm is applied to N-H bond dynamics in the beta-sheet residue
      K19, and the alpha-helix residue A34, of the third immunoglobulin-binding domain
      of streptococcal protein G. The largest contribution to the SRLS TCFs is made by
      mixed anti-correlated D1 and D2 eigenmodes. The next largest contribution is made
      by D1-dominated eigenmodes. Eigenmodes dominated by the local motion contribute
      appreciably to A34 and marginally to K19. Correlated D1 and D2 eigenmodes
      contribute exclusively to K19 and do not contribute above 1% to A34. The
      differences between K19 and A34 are delineated and rationalized in terms of the
      best-fit SRLS parameters and mode-mixing. It may be concluded that eigenmode
      analysis is complementary and supplementary to data-fitting-based analysis.

PMID- 24329097
TI  - Reorientation of the helix of the tryptophan-rich gp41W peptide from HIV-1 at
      interfaces.
AB  - The glycoprotein gp41 from the Human Immunodeficiency Virus type 1 (HIV-1) has an
      amino acid sequence enriched in tryptophan residues, the so-called gp41W peptide
      (i.e., KWASLWNWFNITNWLWYIK) and plays a crucial role in HIV-1 host cell
      infection. Using the coupling of Second Harmonic Generation targeting the
      tryptophan residues with lateral surface tension measurements, we investigate the
      interaction of gp41W with a neat air/water and a lipid/water interfaces. At the
      air/water interface, gp41W presents a well-defined orientation and this
      orientation is strongly modified at the lipid/water interface, depending on the
      surface pressure. These results show that this strategy is well suited to monitor
      tryptophan containing alpha-helices orientation at lipid/water interfaces. 

PMID- 24329101
TI  - Diurnal variation of arterial stiffness in healthy individuals of different ages
      and patients with heart disease.
AB  - BACKGROUND: Arterial stiffness can be measured using various non-invasive
      methods. It is not well established whether it is necessary to standardize the
      time of the day when performing these measurements. The aim of the present study
      is to examine the effect of daytime on arterial stiffness in individuals with and
      without heart disease. METHODS: We investigated the diurnal variation of cardio
      ankle vascular index (CAVI) and carotid femoral pulse wave velocity (cfPWV). CAVI
      and cfPWV were measured in 70 participants (23 healthy young individuals [HY], 22
      healthy elderly individuals [HE], 25 patients with heart disease [HD]) at 09:00,
      13:00 and 17:00 h. RESULTS: There was a significant diurnal variation in CAVI
      with the highest values at 09:00 h in both univariate and multivariate analysis.
      After adjusting for age, sex and MAP (mean arterial pressure), CAVI maintained a
      significant highest values at 09:00 h, which was 4% higher than at 13:00 h (p =
      0.022) and 5% higher than at 17:00 h (p = 0.002). However, a lack of diurnal
      variation was found in cfPWV in multivariate analysis in our study population.
      CONCLUSION: Our findings suggest that it does not appear mandatory to measure
      cfPWV at the same time of day. However, standardizing the time of day for CAVI is
      important in routine clinical practice and longitudinal studies.

PMID- 24329102
TI  - Dichlorination of (hexadehydro-Diels-Alder generated) benzynes and a protocol for
      interrogating the kinetic order of bimolecular aryne trapping reactions.
AB  - The efficient dichlorination of benzynes prepared by the hexadehydro-Diels-Alder
      (HDDA) reaction is reported. Cycloisomerization of a triyne substrate in the
      presence of dilithium tetrachlorocuprate is shown to provide dichlorinated
      products A by capture of the benzyne intermediate. A general strategy for
      discerning the kinetic order of an external aryne trapping agent is presented. It
      merely requires measurement of the competition between bimolecular vs
      unimolecular trapping events (here, dichlorination vs intramolecular Diels-Alder
      (IMDA) reaction to give A vs B, respectively) as a function of the concentration
      of the trapping agent. 

PMID- 24329103
TI  - Intimate partner violence against female sex workers in Mombasa, Kenya.
AB  - Female sex workers are known to be at risk of intimate partner violence (IPV)
      from numerous sources including clients, pimps, boyfriends and husbands. Better
      understanding the factors associated with IPV in this population will enhance
      prevention efforts. This work examines baseline survey data collected as part of
      a randomised controlled trial for an alcohol-harm reduction intervention. The
      study sample included 619 sex workers. IPV was common in this sample, with 78.7%
      of women reporting any IPV in the last 30 days. Multivariate logistic regression
      results indicated that supporting one to two other people, experiencing child
      abuse, witnessing mother abuse, and greater alcohol consumption were risk factors
      for IPV in our sample. Women who frequented Population, Health and Integrated
      Assistance (APHIA) II drop-in centres located along transport corridors were also
      at greater risk of recent IPV, as compared with those who frequented other drop
      in centres. Only one protective effect was identified in this study: condom use
      at last sex with a non-paying partner was associated with less recent IPV. Health
      programmes for women sex workers in Mombasa and elsewhere need to expand beyond
      HIV prevention - they need to incorporate information on violence prevention and
      treatment referrals, as well as information on alcohol harm reduction.

PMID- 24329104
TI  - Electron-beam patterning of polymer electrolyte films to make multiple nanoscale
      gates for nanowire transistors.
AB  - We report an electron-beam based method for the nanoscale patterning of the
      poly(ethylene oxide)/LiClO4 polymer electrolyte. We use the patterned polymer
      electrolyte as a high capacitance gate dielectric in single nanowire transistors
      and obtain subthreshold swings comparable to conventional metal/oxide wrap-gated
      nanowire transistors. Patterning eliminates gate/contact overlap, which reduces
      parasitic effects and enables multiple, independently controllable gates. The
      method's simplicity broadens the scope for using polymer electrolyte gating in
      studies of nanowires and other nanoscale devices. 

PMID- 24329105
TI  - Histopathological analysis and clinical correlation of drug reaction with
      eosinophilia and systemic symptoms (DRESS).
AB  - BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a
      severe cutaneous adverse drug reaction. However, its histopathological features
      have not been well defined. OBJECTIVES: To identify the clinicohistopathological
      findings of DRESS, and analyse the cutaneous histopathological changes observed
      in DRESS compared with those observed in maculopapular exanthema (MPE). METHODS:
      In a retrospective study, conducted at Chang Gung Memorial Hospital (Taiwan)
      between 2001 and 2011, we compared the clinicohistopathological features of 32
      patients with probable/definite DRESS (defined by the RegiSCAR scoring system)
      with those of 17 patients with MPE. RESULTS: The major pathological changes
      observed in patients with DRESS included dyskeratosis (97%), epidermal spongiosis
      (78%), interface vacuolization (91%), perivascular lymphocytic infiltration (97%)
      and eosinophilic infiltration (72%). Many pathological features were common to
      both MPE and DRESS. However, severe dyskeratosis, epidermal spongiosis and severe
      interface vacuolization were significantly more prominent in cases of DRESS (P <
      0.05). The presence of severe dyskeratosis was significantly associated with the
      clinical severity of renal impairment (P = 0.01). CONCLUSIONS: The severe
      dyskeratosis detected in patients with DRESS may correlate with a greater extent
      of systemic involvement compared with that noted in MPE. However, the
      histopathological changes associated with DRESS are not entirely specific.

PMID- 24329106
TI  - The Affordable Care Act and integrated care.
AB  - The Patient Protection and Affordable Care Act (ACA) of 2010 offers a
      comprehensive, integrated health insurance reform program for those who are
      eligible to enroll. A core feature of the ACA is the integration of primary
      health, behavioral health, and related services in a new national program for the
      first time. This article traces the history of past federal services integration
      efforts and identify varying approaches for implementing them to improve care,
      especially for underserved populations. The business case for integrated care,
      reducing escalating health care costs and overcoming barriers to implementation,
      is also discussed. 

PMID- 24329107
TI  - Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin
      disease, Netherton syndrome.
AB  - Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations
      in the serine protease inhibitor Kazal type 5 gene (SPINK5), which encodes for a
      serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI).
      Patients with NS have defective keratinization, hair shaft defects, recurrent
      infections, atopy, and a predisposition to skin malignancies. Historically, 1 in
      10 infants has died before their first birthday. Currently, there are no proven
      treatments to cure this condition. A SIN-lentiviral vector encoding the codon
      optimized SPINK5 gene under the control of a 572 bp element derived from the
      human involucrin promoter can confer compartment-specific LEKTI expression in NS
      keratinocytes with restoration of normal skin architecture. Here we detail a
      study protocol for a phase I trial for feasibility and safety evaluations of
      autologous epidermal sheets generated from ex vivo gene-corrected keratinocyte
      stem cells, which will be grafted onto patients with mutation-proven NS.

PMID- 24329108
TI  - "My view that disability is okay sometimes clashes": experiences of two disabled
      occupational therapists.
AB  - AIMS: While disability is the focus of much attention in occupational therapy,
      there has been little attention paid to disability within the profession.
      Disabled therapists not only bring valuable perspectives on disability, but also
      pose important challenges to taken-for-granted assumptions about impairment and
      disability within the profession. At the same time, their cultural beliefs and
      values may clash with core assumptions of the profession. METHODS: This study
      analyses interview data from two disabled occupational therapists, part of a
      larger study with cultural minority therapists. Semi-structured interviews
      explored their experiences of professional practice in the context of societal
      belief in the superiority of non-disabled and "normal" ways of doing and being.
      MAJOR FINDINGS: Some cultural values of participants clashed with the values and
      beliefs of their profession, particularly concerning independence. Negative
      attitudes of colleagues and managers were the key barriers to practice. The
      responsibility for bridging the disabled/non-disabled cultural divide rested with
      the disabled therapists, exacerbating inequity. Nonetheless, these therapists
      believed their disability experiences had advantages for practice. CONCLUSIONS:
      Disabled therapists may be required to engage in invisible work to communicate
      across cultural differences, and to educate others. Respectful openness to
      difference could enhance the practice competence of both disabled therapists and
      their non-disabled colleagues. This demands critical reflexive attention to
      ableism within the profession.

PMID- 24329109
TI  - The metabolism of anthocyanins.
AB  - Anthocyanins are the largest group of water-soluble pigments in the plant
      kingdom. As with other polyphenols, they express antioxidant activity in vivo.
      Anthocyanins are associated with reduced risk of some several diseases, such as
      atherosclerosis and diabetes. Their beneficial health effects depend on the
      efficiency of their absorption. The intake of anthocyanins from the
      gastrointestinal lumen into the blood is likely to occur through the epithelium
      of the stomach, intestine and colon. The mechanisms of absorption differ from
      site to site, and they depend on the structure of the molecules that are
      absorbed. In plasma, anthocyanins can be found in their intact form, or as the
      corresponding phenolic acids and aldehydes, and also as methyl, sulfate and
      glucuronyl conjugates. Although aglycones can exist in plasma for short times,
      they are prone to degrade due to their instability; however, binding with
      proteins might preserve their intact structures. The plasma concentrations of
      anthocyanins are low, and efficient transport is crucial for their accessibility
      to tissues. Anthocyanins can cross the blood-brain barrier. However, besides
      their reduction of oxidative stress, the mechanisms behind their influence on
      neuronal activity are not completely understood. In this mini-review, we provide
      a short overview of the bioavailability, metabolic products, and transport
      processes of anthocyanins. 

PMID- 24329110
TI  - Prodrugs of quercetin and resveratrol: a strategy under development.
AB  - The biochemical activities of plant flavonoids and stilbenoids point to many
      health-related applications, hampered however by a low bioavailability associated
      with rapid metabolic modification. A possible approach to overcome this obstacle
      is the development of prodrugs. In this review we provide some background
      information and summarize the efforts made so far to obtain suitable precursors
      of the two best known model polyphenols belonging to the classes just mentioned,
      quercetin and resveratrol. Prodrug design needs to take into account two key
      aspects: the nature of the chemical bond linking the core molecule to the
      protecting substituent, and the substituent itself, which can impart desirable
      physico-chemical properties. Only recently a systematic study of the several
      possible combinations has begun. Most bond systems tested so far appear to be
      either too stable or too unstable under physiological conditions. A range of
      substituent moieties is available, allowing the modulation of properties such as
      water solubility and the ability to permeate biomembranes. Work so far has been
      largely performed in vitro, and more in vivo experiments are definitely needed
      for a reliable assessment of the potentialities of the classes of prodrugs
      produced so far and of those still awaiting creation. 

PMID- 24329111
TI  - Downstream carcinogenesis signaling pathways by green tea polyphenols: a
      translational perspective of chemoprevention and treatment for cancers.
AB  - Green tea is one of the most popular beverages around the world. For several
      decades, numerous epidemiological, preclinical and clinical studies have
      demonstrated that green tea polyphenols (GTPs), especially epigallocatechin-3
      gallate (EGCG) have cancer-preventing effects on various cancers. In this review,
      we present inhibition of carcinogenesis in different animal models by GTPs or
      EGCG, including prostate cancer, bladder cancer, breast cancer, intestinal
      cancer, colon cancer, gastric cancer, lung cancer, oral cancer and skin cancer.
      In vitro studies showed that GTPs/EGCG potently induces apoptosis, cell cycle
      arrest and suppresses metastasis in tumor cells but not in their normal cell
      counterparts. The molecular mechanisms of these activities are discussed in
      detail to elucidate GTPs/EGCG downstream carcinogenesis signaling pathways and
      their values of perspective of chemoprevention and treatment for cancers. 

PMID- 24329112
TI  - Advance in methods studying the pharmacokinetics of polyphenols.
AB  - Significant advances have been achieved during the past decade concerning the
      metabolism of polyphenol compounds in vitro, but scarce data has been presented
      about what really happens in vivo. Many studies on polyphenols to date have
      focused on the bioactivity of one specific molecule in aglycone form, often at
      supraphysiological doses, whereas foods contain complex, often poorly
      characterized mixtures with multiple additive or interfering activities. Whereas
      most studies up to the middle-late 1990s measured total aglycones in plasma and
      urine, after chemical or enzymatic deconjugation, or both, several recent works
      now report the polyphenol conjugate composition of plasma, urine, feces and/or
      tissues, after the administration of pure polyphenols or polyphenol-rich
      matrices. HPLC methods with electrochemical, mass spectrometric and fluorescence
      detection have adequate sensitivity. LC/UV-Vis methods have also been widely
      reported, but they are much less sensitive. Compared with electro-chemical and
      fluorescence detection, MS can quantify analytes without chromatographic
      separation, which leads to high throughput, presenting itself as the best choice
      to date. Regarding the experimental model to monitor the bioavailability of
      phenolic compounds, most published studies are based on human and animal models,
      with the majority using rodents, primates and recently the nematode
      Caenorhabditis elegans. This review focuses on the fundamentals of
      pharmacokinetic methods from the last 15 years and how the results are evaluated
      and validated. The types of analytical methods, animal models and biological
      matrices were used to better elucidate pharmacokinetics of polyphenols. 

PMID- 24329113
TI  - Pharmacogenetic variation and metformin response.
AB  - Diabetes is a major health problem worldwide, and metformin, a traditional oral
      anti-hyperglycemic drug, is now believed to be the most widely prescribed
      antidiabetic drug. Metformin acts primarily by inhibiting hepatic glucose
      production and improving insulin sensitivity. Metformin is absorbed predominately
      by the small intestine and excreted in an unaltered form in the urine. The
      pharmacokinetics of metformin is primarily determined by membrane transporters,
      including the plasma membrane monoamine transporter (PMAT), the organic cation
      transporters (OCTs), the multidrug and toxin extrusion (MATE) transporters, and
      the critical protein kinase AMPactivated protein kinase (AMPK). PMAT may play a
      role in the uptake of metformin from the gastrointestinal tract, while OCTs
      mediate the intestinal absorption, hepatic uptake, and renal excretion of
      metformin. MATEs are believed to contribute to the hepatic and renal excretion of
      the drug. The pharmacologic effects of metformin are primarily exerted in the
      liver, at least partly via the activation of AMPK and the subsequent inhibition
      of gluconeogenesis. A considerable amount of pharmacogenetic research has
      demonstrated that genetic variation is one of the major factors affecting
      metformin response. Moreover, it has become increasingly clear that membrane
      transporters are important determinants of the pharmacokinetics of metformin. In
      this review, we will discuss the genetic variants of major transporters that
      purportedly determine the pharmacokinetics of metformin in terms of drug
      bioavailability, distribution, and excretion, such as PMAT, OCTs, and MATEs.
      Understanding how genetic variation affects metformin response will help promote
      more effective use of the drug for the treatment of type 2 diabetes (T2D). 

PMID- 24329117
TI  - Polarization switching ability dependent on multidomain topology in a uniaxial
      organic ferroelectric.
AB  - The switching of electric polarization induced by electric fields, a fundamental
      functionality of ferroelectrics, is closely associated with the motions of the
      domain walls that separate regions with distinct polarization directions.
      Therefore, understanding domain-walls dynamics is of essential importance for
      advancing ferroelectric applications. In this Letter, we show that the topology
      of the multidomain structure can have an intrinsic impact on the degree of
      switchable polarization. Using a combination of polarization hysteresis
      measurements and piezoresponse force microscopy on a uniaxial organic
      ferroelectric, alpha-6,6'-dimethyl-2,2'-bipyridinium chloranilate, we found that
      the head-to-head (or tail-to-tail) charged domain walls are strongly pinned and
      thus impede the switching process; in contrast, if the charged domain walls are
      replaced with electrically neutral antiparallel domain walls, bulk polarization
      switching is achieved. Our findings suggest that manipulation of the multidomain
      topology can potentially control the switchable polarization. 

PMID- 24329114
TI  - Post-translational and post-transcriptional modifications of pregnane X receptor
      (PXR) in regulation of the cytochrome P450 superfamily.
AB  - Pregnane X receptor (PXR) is a member of the nuclear receptor (NR) superfamily of
      ligand-activated transcription factors and is activated by a huge variety of
      endobiotics and xenobiotics, including many clinical drugs. PXR plays key roles
      not only as a xenosensor in the regulation of both major phase I and II drug
      metabolism and transporters but also as a physiological sensor in the modulation
      of bile acid and cholesterol metabolism, glucose and lipid metabolism, and bone
      and endocrine homeostasis. Post-translational modifications such as
      phosphorylation have been shown to modulate the activity of many NRs, including
      PXR, and constitute an important mechanism for crosstalk between signaling
      pathways and regulation of genes involved in both xenobiotic and endobiotic
      metabolism. In addition, microRNAs have recently been shown to constitute another
      level of PXR activity regulation. The objective of this review is to
      comprehensively summarize current understanding of post-transcriptional and post
      translational modifications of PXR in regulation of xenobiotic-metabolizing
      cytochrome P450 (CYP) genes, mainly in hepatic tissue. We also discuss the
      importance of PXR in crosstalk with cell signaling pathways, which at the level
      of transcription modify expression of genes associated with some physiological
      and pathological stages in the organs. Finally, we indicate that these PXR
      modifications may have important impacts on CYP-mediated biotransformation of
      some clinically used drugs. 

PMID- 24329115
TI  - Biotransformations of prenylated hop flavonoids for drug discovery and
      production.
AB  - In this review we aim to present current knowledge on biotransformation of
      flavonoids from hop cones with respect to type of product, catalyst and
      conversion. Subsequently, a comparative analysis of biological activity of
      prenylated hop flavonoids and their biotransformation products has been performed
      in order to indicate these research efforts that have good potential for
      application in pharmaceutical industry. There is increasing evidence that the
      products of biotransformation of hop prenylflavonoids, which have been little
      studied until recently, can be used as drugs or drug ingredients and also as
      standards of human drug metabolites. They can also serve as an inspiration for
      the design and chemical synthesis of new derivatives with higher or different
      biological activity. Nevertheless, much additional work, among others on
      determining the mechanism of action in in vivo systems, is needed to open up the
      way to biomedical application of these compounds. 

PMID- 24329118
TI  - Delirium due to intoxication from the novel synthetic tryptamine 5-MeO-DALT.
AB  - Synthetic tryptamines have gained popularity for their hallucinogenic properties,
      unscheduled status, and availability from "head shops" and through the internet.
      Here, we present a case of synthetic tryptamine-induced delirium secondary to 5
      MeO-DALT ingestion in a previously healthy young male. 5-MeO-DALT led to the
      hospitalization of our patient after ingestion of a standard dose, presenting
      with extreme agitation, tachycardia, diaphoresis, and combativeness leading to
      physical restraint and intravenous sedation. A search of PubMed, Ovid, and Google
      Scholar for keywords of "5-MeO-DALT," "5-methoxy-N,N-diallyltryptamine," or "Lucy
      N-Nate" found no case reports or clinical articles in the literature. Rapid
      emergence and commercialization of this novel synthetic tryptamine 5-MeO-DALT
      points to the importance of health care and forensic professionals keeping
      abreast of the latest drugs of abuse and their clinical features. The authors
      hope this report leads the way in disseminating the potential risks associated
      with unscheduled and unregulated substances, synthetic tryptamines such as 5-MeO
      DALT in particular. 

PMID- 24329119
TI  - Continuation rates of the subdermal contraceptive Implanon((r)) and associated
      influencing factors.
AB  - OBJECTIVES To investigate the continuation rates of the etonogestrel subdermal
      contraceptive implant among well-informed women, and the reasons for early
      discontinuation. STUDY DESIGN Retrospective consecutive cohort design. METHODS
      Women who had the implant inserted between 1 January 2006 and 1 January 2010 at
      the Atrium Medical Centre, the Netherlands were followed up for at least three
      years. The dates of insertion and removal were recorded, as were the reasons for
      removal. Statistical analysis was performed using the independent samples t-test
      and the Pearson alpha correlation test. RESULTS The implant was inserted in 230
      women. Follow-up was possible in 214 women, with an average age of 26.7 years.
      Most of them were nulliparous and the majority had used a combined oral
      contraceptive, Implanon(r), or Mirena(r) previously. The mean overall
      continuation period was 23.5 months (95% confidence interval: 21.7-25.3), with a
      median of 25 months. The continuation rate after 12 months was 72%; after 24
      months, 53%; and after 36 months, 25%, with all women concerned having a new
      implant placed. The previously used contraceptive method Implanon(r) was
      associated with the highest continuation rates. An erratic bleeding pattern was
      the main reason for early removal. CONCLUSIONS Despite adequate counselling
      before insertion, the continuation rate of the etonogestrel implant was rather
      low compared to those reported by other investigators. The main reason for
      discontinuation was an irregular bleeding pattern.

PMID- 24329120
TI  - Gas-phase reactions and energy transfer at very low temperatures.
AB  - Experimental studies of gas-phase chemical reactions and molecular energy
      transfer at very low temperatures and between electrically neutral species are
      reviewed. Although work of collisionally induced vibrational and rotational
      transfer is described, emphasis is placed on very recent results on the rates of
      free radical reactions obtained by applying the pulsed laser photolysis (PLP)
      laser-induced fluorescence (LIF) technique in a CRESU (Cinetique de Reactions en
      Ecoulement Supersonique Uniforme) apparatus at temperatures as low as 13 K. These
      measurements demonstrate that quite a wide variety of reactions-including those
      between two radicals, those between radicals and unsaturated molecules, and even
      some of those between radicals and saturated molecules-remain rapid at very low
      temperatures. Theoretical efforts to explain some of these results are described,
      as is their impact on attempts to model the synthesis of molecules in
      interstellar clouds. 

PMID- 24329121
TI  - Enhancing the peroxidase activity of cytochrome c by mutation of residue 41:
      implications for the peroxidase mechanism and cytochrome c release.
AB  - The peroxidase activity of cytochrome c may play a key role in the release of
      cytochrome c from the mitochondrial intermembrane space in the intrinsic
      apoptosis pathway. Induction of the peroxidase activity of cytochrome c is
      ascribed to partial unfolding and loss of axial co-ordination between the haem Fe
      and Met80, and is thought to be triggered by interaction of cytochrome c with
      cardiolipin (diphosphatidylglycerol) in vivo. However, the reaction mechanism for
      the peroxidase activity of either native or cardiolipin-bound cytochrome c is
      uncertain. In the present study we analyse the peroxidase activity of human and
      mouse cytochrome c residue 41 variants and demonstrate that stimulation of
      peroxidase activity can occur without prior loss of Fe-Met80 co-ordination or
      partial unfolding. The effects of cardiolipin and mutation of residue 41 are not
      additive, suggesting that cardiolipin stimulates peroxidase activity by the same
      mechanism as residue 41 mutation. Consistent with this, mutation of residue 41
      did not enhance apoptotic release of cytochrome c from mitochondria. We propose
      that mutation of residue 41, and interaction with cardiolipin, increase
      peroxidase activity by altering the 40-57 Omega loop and its hydrogen bond
      network with the propionate of haem ring A. These changes enhance access of
      hydrogen peroxide and substrate to the haem.

PMID- 24329122
TI  - Diastolic and autonomic dysfunction in early cirrhosis: a dobutamine stress
      study.
AB  - OBJECTIVE. Presence of cardiac dysfunction in patients with advanced cirrhosis is
      widely accepted, but data in early stages of cirrhosis are limited. Systolic and
      diastolic functions, dynamics of QT-interval, and pro-atrial natriuretic peptide
      (pro-ANP) are investigated in patients with early stage cirrhosis during maximal
      beta-adrenergic drive. MATERIAL AND METHODS. Nineteen patients with Child A (n =
      12) and Child B cirrhosis (n = 7) and seven matched controls were studied during
      cardiac stress induced by increasing dosages of dobutamine and atropine. RESULTS.
      Pharmacological responsiveness was similar in cirrhosis and controls and the
      heart rate (HR) increased by 66 +/- 15 versus 67 +/- 8 min(-1). HR-blood pressure
      product increased equally by 115% in both cirrhotic patients and controls.
      However, time to resume HR of 100 beats/min was significantly longer in
      cirrhosis, p < 0.01. The QTc interval increased after dobutamine infusion in
      cirrhosis (0.41 +/- 0.02 vs. 0.43 +/- 0.02 s, p = 0.001) but similar
      electrophysiological changes were seen in controls. Cardiac volumes increased
      with the severity of disease. The increased cardiac output was primarily
      attributed to increased stroke volume. The ejection fraction was similar in
      patients and controls. Peak filling rate was longer in cirrhosis compared to
      controls (1.8 +/- 0.4 and 1.4 +/- 0.2 end-diastolic volume/s, p < 0.01). Pro-ANP
      was higher in cirrhosis and increased during stress by 13% compared to 0% in
      controls, p < 0.01. CONCLUSIONS. These findings indicate that patients with early
      stage cirrhosis exhibit early diastolic and autonomic dysfunction as well as
      elevated pro-ANP. However, the cardiac chronotropic and inotropic responses to
      dobutamine stress were normal. The dynamics of ventricular repolarization appears
      normal in patients with early stage cirrhosis.

PMID- 24329123
TI  - Persistence of within-species lineages: a neglected control of speciation rates.
AB  - We present a framework distinguishing three principal controls of speciation
      rate: rate of splitting, level of persistence, and length of speciation duration.
      We contend that discussions on diversification become clearer in the light of
      this framework, because speciation rate variation could be attributed to any of
      these controls. In particular, we claim that the role of persistence of within
      species lineages in controlling speciation rates has been greatly
      underappreciated. More emphasis on the persistence control would change
      expectations of the role of several biological traits and environmental factors,
      because they may drive speciation rate in one direction through the persistence
      control and in the opposite direction through the other two controls. Traits and
      environments have been little studied regarding their influence on speciation
      rate through the persistence control, with climatic fluctuations being a
      relatively well-studied exception. Considering the recent advances in genomic and
      phylogenetic analysis, we think that the time is ripe for applying the framework
      in empirical research. Variation among clades and areas (and thus among traits
      and environments) in the importance of the three rate controls could be addressed
      for example by dating splitting events, detecting within-species lineages, and
      scanning genomes for evidence of divergent selection. 

PMID- 24329125
TI  - The assessment of cognitive errors using an observer-rated method.
AB  - OBJECTIVE: Cognitive Errors (CEs) are a key construct in cognitive behavioral
      therapy (CBT). Integral to CBT is that individuals with depression process
      information in an overly negative or biased way, and that this bias is reflected
      in specific depressotypic CEs which are distinct from normal information
      processing. Despite the importance of this construct in CBT theory, practice, and
      research, few methods are available to researchers and clinicians to reliably
      identify CEs as they occur. METHOD: In this paper, the author presents a rating
      system, the Cognitive Error Rating Scale, which can be used by trained observers
      to identify and assess the cognitive errors of patients or research participants
      in vivo, i.e., as they are used or reported by the patients or participants.
      CONCLUSIONS: The method is described, including some of the more important rating
      conventions to be considered when using the method. This paper also describes the
      15 cognitive errors assessed, and the different summary scores, including valence
      of the CEs, that can be derived from the method.

PMID- 24329126
TI  - Left hemispheric lateral preference and high neuroticism predict disinhibition in
      two go/no-go experiments.
AB  - Although disinhibition is widely implicated in impulse-control-related
      psychopathologies, debate remains regarding the underlying approach and avoidance
      processes of this construct. In two studies, we simultaneously tested three
      competing models in which varying levels of extraversion, neuroticism, and
      hemispheric lateral preference are associated with disinhibition. In both studies
      (Study 1, N = 92; Study 2, N = 124), undergraduate students were randomly
      allocated to one of two versions of the go/no-go task: one where participants
      were primed through reward to make more "go" responses and another where no such
      priming occurred. Neuroticism, extraversion, and hemispheric lateral preference
      measures were also collected. Across both studies, disinhibition was greatest in
      individuals who reported both a left hemispheric lateral preference and high
      neuroticism. This pattern was only found for those who were primed through reward
      to make more "go" responses. There was no association with extraversion. Contrary
      to previous research, our results suggest that left hemispheric asymmetry and
      neuroticism and not extraversion drive disinhibited approach, following the
      establishment of a prepotent approach response set. This has salient implications
      for the theoretical understanding of disinhibited behavior, as well as for the
      study of continued maladaptive approach behavior. 

PMID- 24329127
TI  - BDNF 196 G/A and 270 C/T polymorphisms and susceptibility to Parkinson's disease:
      a meta-analysis.
AB  - ABSTRACT The aim of this study was to explore whether brain-derived neurotrophic
      factor (BDNF) polymorphisms 196 G/A and 270 C/T confer susceptibility to
      Parkinson's disease (PD). The authors conducted a meta-analysis of the
      associations between the BDNF 196 G/A and 270 C/T polymorphisms and PD in
      subjects. They considered 12 studies in the case of the BDNF 196 G/A polymorphism
      and 4 studies in the case of the BDNF 270 C/T polymorphism. Meta-analysis showed
      no association between PD and the BDNF 196A allele in all study subjects (odds
      ratio [OR] = 1.066, 95% CI [0.972, 1.169], p = .173). However, ethnicity-specific
      meta-analysis identified an association between the BDNF 196 AA + AG genotype and
      PD in Europeans, but not in Asians (OR = 1.212, 95% CI [1.007, 1.458], p = .042;
      OR = 1.0567, 95% CI [0.913, 1.221], p = .465). Meta-analysis showed no
      association between PD and the BDNF 270 C/T polymorphism (OR for the T allele =
      1.213, 95% CI [0.923, 1.595], p = .165). This meta-analysis identified an
      association between the BDNF 196 G/A polymorphism in Europeans, but not in
      Asians, but failed to identify an association between the BDNF 270 C/T
      polymorphism and PD. 

PMID- 24329129
TI  - Intravitreal anti-VEGF treatment as adjunctive treatment in the management of
      diabetic retinopathy.

PMID- 24329128
TI  - Frontal lobe epilepsy alters functional connections within the brain's motor
      network: a resting-state fMRI study.
AB  - Patients with frontal lobe epilepsy (FLE) often experience motor deficits, yet
      little is known of the impact of FLE on the activity of motor networks in the
      brain. Resting-state functional magnetic resonance imaging (rs-fMRI) has
      previously demonstrated an association between cognitive deficits in temporal
      lobe epilepsy patients and disruption of activity within pertinent brain
      networks. Hence, in the present study, rs-fMRI was used to determine whether FLE
      is associated with motor network disruption. Seven right-hemisphere FLE patients,
      six left-hemisphere FLE patients, and nine control subjects underwent rs-fMRI.
      Functional connectivity was computed between the sensorimotor cortex
      contralateral to the seizure focus and each voxel in the brain, and then compared
      voxel-by-voxel between patient groups and controls. A laterality index (LI) of
      connectivity between contralateral and ipsilateral sensorimotor cortices was
      calculated to investigate its association with epilepsy duration and seizure
      frequency. Positive laterality indices indicate reduced connectivity, and zero
      values indicate strong connectivity. Connectivity between the left and right
      sensorimotor cortices was significantly reduced in FLE patients compared with
      controls (p<0.05), and LI was positively correlated with the number of lifetime
      seizures (left FLE: rs=0.89, right FLE: rs=1.00). Patients with FLE exhibit
      decreased connectivity within the motor network, in correlation with the number
      of lifetime seizures, thus demonstrating a potential relationship between seizure
      activity and changes in motor network organization. These findings suggest that
      motor network disturbances may in part be responsible for the motor deficits
      observed in FLE patients.

PMID- 24329130
TI  - Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol
      Dispersing: approaches to enhance solubility of a poorly water-soluble gum
      extract.
AB  - Acetyl-11-keto-beta-boswellic acid (AKBA), a gum resin extract, possesses poor
      water-solubility that limits bioavailability and a high melting point making it
      difficult to successfully process into solid dispersions by fusion methods. The
      purpose of this study was to investigate solvent and thermal processing
      techniques for the preparation of amorphous solid dispersions (ASDs) exhibiting
      enhanced solubility, dissolution rates and bioavailability. Solid dispersions
      were successfully produced by rotary evaporation (RE) and KinetiSol(r) Dispersing
      (KSD). Solid state and chemical characterization revealed that ASD with good
      potency and purity were produced by both RE and KSD. Results of the RE studies
      demonstrated that AQOAT(r)-LF, AQOAT(r)-MF, Eudragit(r) L100-55 and Soluplus with
      the incorporation of dioctyl sulfosuccinate sodium provided substantial
      solubility enhancement. Non-sink dissolution analysis showed enhanced dissolution
      properties for KSD-processed solid dispersions in comparison to RE-processed
      solid dispersions. Variances in release performance were identified when
      different particle size fractions of KSD samples were analyzed. Selected RE
      samples varying in particle surface morphologies were placed under storage and
      exhibited crystalline growth following solid-state stability analysis at 12
      months in comparison to stored KSD samples confirming amorphous instability for
      RE products. In vivo analysis of KSD-processed solid dispersions revealed
      significantly enhanced AKBA absorption in comparison to the neat, active
      substance. 

PMID- 24329131
TI  - Effects of sulfasalazine and tofacitinib on the protein profile of articular
      chondrocytes.
AB  - OBJECTIVE: Sulfasalazine (SSZ) and tofacitinib are effective for treating
      rheumatoid arthritis, however, their effects on chondrocytes have not been fully
      understood. We here tried to elucidate their effects on chondrocyte proteins.
      METHODS: We treated chondrocytes from five osteoarthritis patients with IL-1beta,
      IL-1beta+ SSZ, IL-1beta+ tofacitinib, SSZ alone, and tofacitinib alone. Then, we
      compared protein profiles of the chondrocytes using two-dimensional differential
      gel electrophoresis. Further, we identified altered proteins by mass
      spectrometry. RESULTS: Out of 892 detected protein spots, the IL-1beta
      stimulation changed intensity of 43 spots more than 1.3-fold or less than 1/1.3
      fold significantly. SSZ suppressed the IL-1beta-induced intensity alteration in
      16 (37%) out of the 43 protein spots. Tofacitinib suppressed the IL-1beta-induced
      alteration in 4 (9.3%) out of the 43 spots. The production of AMP deaminase 2 and
      procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 were increased by IL-1beta and
      the increase was suppressed by SSZ and by tofacitinib. SSZ alone altered
      intensity of 273 (31%) out of the 852 spots significantly, whereas tofacitinib
      alone altered intensity of only 24 (2.7%) out of them. CONCLUSION: SSZ and, to
      lesser extent, tofacitinib suppress the effects of IL-1beta on the protein
      profiles of chondrocytes. Our data would promote understanding of effects of the
      drugs on chondrocytes.

PMID- 24329132
TI  - A comparison of the effectiveness of low-, moderate- and high-dose ultrasound
      therapy applied in the treatment of myofascial pain syndrome.
AB  - OBJECTIVE: This study aimed to compare and evaluate the effects of ultrasound
      (US) treatment applied at low-, medium- and high-power-pain threshold (HPPT)
      doses to trigger points in the treatment of myofascial pain syndrome (MPS).
      METHODS: The study comprised 61 (40 female and 21 male) patients diagnosed with
      MPS, aged between 18 and 60 years. The patients were randomly allocated to three
      groups for the US application at different dosages. Group I patients received
      treatment of medium-dose US (1.5 Watt/cm(2)), Group II received HPPT US, and
      Group III received low-dose US (0.5 W/cm(2)). The patients were evaluated pre
      treatment and 3 weeks after treatment in respect of visual analogue scale (VAS)
      scores, number of trigger points (NTP), pressure pain threshold (PPT), Range of
      Tragus-Acromioclavicular joint (RT-AJ) and neck pain disability scores (NPDS).
      RESULTS: A significant improvement was determined after treatment in all scores
      except PPT in Group I, in all scores in Group II, and only in the VAS score in
      Group III. When the groups were compared post-treatment in respect of improvement
      in NTP, VAS, RT-AJ and NPDS scores, Group II showed significant superiority over
      Group I, and Group I was determined to have significant superiority over Group
      III in respect of VAS, RT-AJ and NPDS scores (p < 0.05). CONCLUSIONS: In the
      treatment of MPS, US therapy at HPPT dose can be considered as an alternative
      therapy method, which is more economical and more effective than low-dose and
      conventional US therapy.

PMID- 24329133
TI  - Predictive value of casual ECG-based resting heart rate compared with resting
      heart rate obtained from Holter recording.
AB  - BACKGROUND: Elevated resting heart rate (RHR) is associated with cardiovascular
      mortality and morbidity. Assessment of heart rate (HR) from Holter recording may
      afford a more precise estimate of the effect of RHR on cardiovascular risk, as
      compared to casual RHR. Comparative analysis was carried out in an age-stratified
      subsample of 131 subjects in the Copenhagen City Heart Study (CCHS). METHODS:
      Casual RHR was assessed from electrocardiograms recorded during clinical
      assessment. Hourly daytime HRs were mapped by Holter recording. Holter RHR was
      defined as the average of the lowest 3 hourly HRs recorded and mean HR calculated
      from all daytime HRs. Follow-up was recorded from public registers. Outcome
      measure was hazard rate for the combined endpoint of cardiovascular mortality,
      non-fatal heart failure and non-fatal acute myocardial infarction. Comparison of
      casual RHR, Holter RHR and mean HR by Multivariate Cox regression was performed.
      RESULTS: A total of 57 composite endpoints occurred during 17.1 years of follow
      up. Regression analysis suggests correlation between Casual RHR and Holter RHR.
      Multivariate Cox regression analysis adjusted for gender and age demonstrated
      hazard rates of 1.02 (p = 0.079) for casual RHR, 1.04 (p = 0.036*) for Holter
      RHR, and 1.03 (p = 0.093) for mean HR for each 10 beat increment in HR.
      CONCLUSIONS: In a comparative analysis on the correlation and significance of
      differing RHR measurement modalities RHR measured by 24-hour Holter recording was
      found to be marginally superior as a predictor of cardiovascular morbidity and
      mortality. The results presented here do not however warrant the abandonment of a
      tested epidemiological variable.

PMID- 24329134
TI  - Fluence-dependent singlet exciton dynamics in length-sorted chirality-enriched
      single-walled carbon nanotubes.
AB  - We utilize individualized, length-sorted (6,5)-chirality enriched single-walled
      carbon nanotubes (SWNTs) having dimensions of 200 and 800 nm, femtosecond
      transient absorption spectroscopy, and variable excitation fluences that modulate
      the exciton density per nanotube unit length, to interrogate nanotube
      exciton/biexciton dynamics. For pump fluences below 30 MUJ/cm(2), transient
      absorption (TA) spectra of (6,5) SWNTs reveal the instantaneous emergence of the
      exciton to biexciton transition (E11 -> E11,BX) at 1100 nm; in contrast, under
      excitation fluences exceeding 100 MUJ/cm(2), this TA signal manifests a rise time
      (tau rise ~ 250 fs), indicating that E11 state repopulation is required to
      produce this signal. Femtosecond transient absorption spectroscopic data acquired
      over the 900-1400 nm spectral region of the near-infrared (NIR) region for (6,5)
      SWNTs, as a function of nanotube length and exciton density, reveal that over
      time delays that exceed 200 fs exciton-exciton interactions do not occur over
      spatial domains larger than 200 nm. Furthermore, the excitation fluence
      dependence of the E11 -> E11,BX transient absorption signal demonstrates that
      relaxation of the E11 biexciton state (E11,BX) gives rise to a substantial E11
      state population, as increasing delay times result in a concomitant increase of
      E11 -> E11,BX transition oscillator strength. Numerical simulations based on a
      three-state model are consistent with a mechanism whereby biexcitons are
      generated at high excitation fluences via sequential SWNT ground- and E11-state
      excitation that occurs within the 980 nm excitation pulse duration. These studies
      that investigate fluence-dependent TA spectral evolution show that SWNT ground ->
      E11 and E11 -> E11,BX excitations are coresonant and provide evidence that E11,BX
      -> E11 relaxation constitutes a significant decay channel for the SWNT biexciton
      state over delay times that exceed 200 fs, a finding that runs counter to
      assumptions made in previous analyses of SWNT biexciton dynamical data where
      exciton-exciton annihilation has been assumed to play a dominant role.

PMID- 24329135
TI  - Matrix dimensions, stiffness, and structural properties modulate spontaneous
      chondrogenic commitment of mouse embryonic fibroblasts.
AB  - Experimental models for cartilage and bone development have been studied in order
      to understand the biomechanical and biological parameters that regulate skeletal
      tissue formation. We have previously described that when mouse embryonic
      fibroblasts (MEFs) were cultured in a three-dimensional (3D)-soft self-assembling
      peptide nanofiber, the system engaged in a spontaneous process of cartilage-like
      formation evidenced by the expression of Sox9, Collagen type II, and
      proteoglycans. In the present work, we studied the influence that matrix
      mechanical properties have in modulating lineage commitment in an in vitro model
      of chondrogenesis. This effect was observed only when MEFs were cultured at low
      elastic modulus values (~ 0.1 kPa). Interestingly, under these conditions, the
      system expressed the chondrogenic inductor BMP4 and its antagonist Noggin. On the
      other hand, at higher elastic modulus values (~ 5 kPa), the system expressed
      Noggin but not BMP4, and did not engage in chondrogenesis, which suggest that the
      balance between bone morphogenetic protein/Noggin could be implicated in the
      chondrogenic process. Finally, no evidence of hypertrophy was detected under the
      conditions tested (by assessing expression of Collagen type X and Runx2) unless
      we challenged the system by co-culturing it with endothelial cells. Importantly,
      under these new conditions, the system underwent spontaneous matrix calcium
      mineralization. These results suggest that the 3D-system described here is
      sensitive to respond to environmental changes such as biomechanical and
      biological cues.

PMID- 24329136
TI  - Practical and cost-effective manufacturing route for the synthesis of a beta
      lactamase inhibitor.
AB  - Compound 1, a potent and irreversible inhibitor of beta-lactamases, is in
      clinical trials with beta-lactam antibiotics for the treatment of serious and
      antibiotic-resistant bacterial infections. A short, scalable, and cost-effective
      route for the production of this densely functionalized polycyclic molecule is
      described. 

PMID- 24329137
TI  - Everyday technology use among people with mental retardation: relevance,
      perceived difficulty, and influencing factors.
AB  - BACKGROUND: While the development and possibilities of technology today are
      commonly regarded to be unlimited, knowledge regarding the technological needs of
      people with mental retardation is fairly limited. The aim of this study was to
      enhance knowledge of perceived relevance and difficulty in using everyday
      technology (ET) such as stoves, cell phones, and elevators in adults with mental
      retardation. METHODS: 120 participants with different levels of mental
      retardation were interviewed with the Everyday Technology Use Questionnaire
      (ETUQ) about their use of such technologies in their everyday life. Analyses of
      variance, post hoc tests, and regression analyses were used to explore the data.
      RESULTS AND CONCLUSIONS: Participants with moderate and severe mental retardation
      differed in mean perceived difficulty from those with mild mental retardation,
      suggesting that increased perceived difficulty in ET use is related to the level
      of mental retardation. Differences between groups were also found in the
      proportion of items that were relevant for each person. The variables Level of
      Mental Retardation, Additional Disabilities, and Proportional Relevance of ET
      Items could together predict 67.2% of the variation in perceived difficulty in
      technology use. The findings also indicate that age, housing, gender, and
      geographical district do not covariate with perceived difficulty in ET use.

PMID- 24329138
TI  - Gene therapy briefs.

PMID- 24329139
TI  - Seeking a cure for the royal pain.

PMID- 24329140
TI  - Retraction of: Novel, small molecule induced GABA-hATSCs for targeting of
      neuropathic pain.

PMID- 24329141
TI  - Traditional medicine: a historical appraisal.

PMID- 24329142
TI  - Exercise preconditioning improves behavioral functions following transient
      cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.
AB  - BACKGROUND: There is evidence that exercise decreases ischemia/reperfusion injury
      in rats. Since behavioral deficits are the main outcome in patients after stroke,
      our study was designed to investigate whether exercise preconditioning improves
      the acute behavioral functions and also brain inflammatory injury following
      cerebral ischemia. METHODS: Male rats weighing 250-300 g were randomly allocated
      into five experimental groups. Exercise was performed on a treadmill 30min/day
      for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition
      memory was assessed by novel object recognition task (NORT) and step-through
      passive avoidance task. Sensorimotor function and motor movements were evaluated
      by adhesive removal test and ledged beam-walking test, respectively. Brain
      inflammatory injury was evaluated by histological assessment. RESULTS: In NORT,
      the discrimination ratio was decreased after ischemia (P < 0.05) and exercise
      preconditioning improved it in ischemic animals. In the passive avoidance test, a
      significant reduction in response latency was observed in the ischemic group.
      Exercise preconditioning significantly decreased the response latency in the
      ischemic rats (P < 0.001). In the adhesive removal test, latency to touch and
      remove the sticky labels from forepaw was increased following induction of
      ischemia (all P < 0.001) and exercise preconditioning decreased these indices
      compared to the ischemic group (all P < 0.001). In the ledged beam-walking test,
      the slip ratio was increased following ischemia (P < 0.05).  In the ischemia
      group, marked neuronal injury in hippocampus was observed. These
      neuropathological changes were attenuated by exercise preconditioning (P <
      0.001). CONCLUSION: Our results showed that exercise preconditioning improves
      behavioral functions and maintains more viable cells in the dorsal hippocampus of
      the ischemic brain.

PMID- 24329143
TI  - Localization of H.pylori within the vacuole of Candida yeast by direct
      immunofluorescence technique.
AB  - BACKGROUND: Reports indicate that H.pylori is able to invade the eukaryotic cells
      and establish inside their vacuoles. In this study, FITC-conjugated IgY-Hp was
      used to localize H.pylori inside the vacuole of Candida yeast. Presence of
      intracellular H.pylori inside the new generations of yeast cells was also
      examined by light microscopy and Live/Dead BacLight staining method. METHODS: A
      single colony of fresh yeast culture was cultivated in a 100-ul medium containing
      yeast extract and N-acetylglucoseamine supplemented with fetal bovine serum.
      After 12-hr incubation at 37C, FITC-conjugated IgY-Hp was added. After 3 hours,
      10 uL of yeast suspension was smeared on a glass slide, air-dried and examined by
      fluorescent microscopy. Wet mounts of yeast culture and Live/Dead BacLight
      stained preparations were examined by light and fluorescent microscopy,
      respectively. Photographs were taken from the fast-moving H.pylori inside the
      yeast vacuoles. RESULTS: Fluorescent microscopy showed that FITC-conjugated IgY
      Hp could enter yeast cells and specifically react with H.pylori, localizing the
      bacterium inside the yeast vacuole. Photographs taken from wet mounts observed by
      light and fluorescent microscopy showed fast-moving H.pylori cells in the
      vacuole of mother as well as daughter yeast cells. The intravacuolar H.pylori
      cells stained green, showing their viability. CONCLUSION: Intracellular life of
      prokaryotes inside eukaryotes has been described as an evolutionary phenomenon
      with a great impact on bacterial persistence despite environmental stresses.
      Results of this study demonstrated the specific interaction of FITC-conjugated
      IgY-Hp with H.pylori cells and the bacterial localization inside the Candida
      yeast vacuole. The intracellular bacteria were viable and existed in the vacuole
      of next generations of yeast cells. It appears that H.pylori is well-equipped to
      dwell within the vacuole of eukaryotic cells where it is protected from stressful
      conditions, including antibacterial therapy. Presence of H.pylori inside the
      vacuole of new generations of yeasts demonstrates the intimate relationship
      between the two microorganisms, resulting in bacterial inheritance as part of the
      vacuolar content of yeast cells.

PMID- 24329144
TI  - Cannabinoid system of the lateral septum in the modulation of anxiety-like
      behaviors in rats.
AB  - BACKGROUNDS: A large body of evidence suggests that the cannabinoid CB1 receptor
      plays a key role in the regulation of emotional behaviors. The present study was
      designed to evaluate the effects of CB1 agonist and antagonist on anxiety-like
      behaviors in the lateral septum (LS) region of the rat brain using elevated plus
      maze test. METHODS: Rats were anesthetized with ketamine and xylazine and special
      cannulas were inserted stereotaxically into the LS region. After 1 week of
      recovery, the effects of intra-LS administration of the CB1 receptor agonist, WIN
      55,212-2 and CB1 receptor antagonist, AM251, on %OAT and %OAE were measured.
      Moreover, the effects of pretreatment with AM251 on the response induced by intra
      LS administration of WIN 55,212-2 were also assessed. RESULTS: Intra-LS
      administration of WIN 55,212-2 (0.001, 0.005 and 0.5MUg/rat) decreased the %OAT
      and %OAE but not locomotor activity, showing an anxiogenic-like response. Intra
      LS injection of different doses of AM251 (0.001, 0.01 and 0.1 ug/rat) did not
      significantly alter the anxiety-like parameters on the plus-maze test. However,
      intra-LS injections of AM251 (0.01 ug/rat) significantly reversed WIN 55,212-2
      induced anxiogenic-like effects. CONCLUSIONS: The results suggest that the
      cannabinoid system of the lateral septum modulates anxiety-like behavior through
      CB1 receptor.

PMID- 24329145
TI  - Stewardship of National Oral Health system in Iran: its strengths and weaknesses.
AB  - AIMS: In this study, we assess the strengths, challenges and opportunities
      regarding the oral health system stewardship in Iran. METHODS: A mixed
      methodology was used, comprised of a quantitative questionnaire using the
      functional standards, semi structured interviews with key stakeholders and
      document review. The level of current attainments of each standard was determined
      based on a Likert-type scale. Literature review was completed to find official
      documents of national organizations. RESULTS: The responsibility of policy
      development of oral health care at the national level mostly falls on the Oral
      Health Bureau. This office has formulated a strategic plan for its policy-making
      and has considered the required capacity to implement them. However, the Bureau
      has some problems in enforcing its regulatory framework, especially in the
      private sector. There are rigorous problems in managing information and using
      them for evidence-based decision making. Setting and allocation of operational
      budgets for implementing the policies is only partially attained, as is
      monitoring and evaluating the performance. CONCLUSIONS: While the Ministry of
      Health and Medical Education has achieved some stewardship measures, it still
      needs further improvements in the oral health system. It needs to strengthen its
      information system and its executive capacity to implement the proposed
      regulations. The Ministry must improve accountability in the oral health system,
      especially the provider accountability.

PMID- 24329146
TI  - Exfoliative cytology of oral mucosa among smokers, opium addicts and non-smokers:
      a cytomorphometric study.
AB  - BACKGROUND: The present study was conducted to evaluate keratinization as well as
      nuclear and cytoplasmic changes of oral epithelial cells among smokers, opium
      addicts and non-smokers through exfoliative cytology technique. METHODS: Smears
      of buccal mucosa and mouth floor were collected from 300 males (100 smokers, 100
      opium addicts and 100 non-smokers). The nucleus and cytoplasm sizes were
      determined using image analysis software. Data was analyzed with Mann-Whitney
      test and Student's t-test on SPSS version 13 statistical software. Statistical
      significance was defined as P < 0.05. RESULTS: The results revealed statistically
      significant differences in cellular and nuclear size and the nuclear/cytoplasmic
      ratio between smokers, opium addicts and non-smokers in different age groups. The
      mean size of the nucleus compared to that of cytoplasm was significantly higher
      in smokers and opium addicts compared to non-smokers after correction for age.
      CONCLUSION: The results of this study indicate different rates of epithelial cell
      keratinization in oral cavity among smokers, opium addicts and non-smokers. Also,
      our results suggest a possible relationship between the number of cigarettes per
      day, daily opium consumption and an increase in the rate of cellular
      proliferation of oral mucosal cells. The present study indicated a decrease in
      cellular diameter as well as an increase in nuclear diameter and
      nuclear/cytoplasmic ratio in smears taken from both smokers and opium addicts
      compared to non-smokers.

PMID- 24329147
TI  - Sense and nonsense in the practice of medicine a critique of traditional Iranian
      medicine.

PMID- 24329148
TI  - Impact of sanctions on procurement of medicine and medical devices in Iran; a
      technical response.
AB  - Following recent sanctions on foreign trade, financial and banking services, Iran
      has faced major difficulties for importing medicines (both finished products and
      pharmaceutical raw materials) and medical devices. Problems with money transfer
      have made it extremely lengthy in time to import medicine and medical devices and
      these have negatively affected access to and affordability of medicines. Quality
      of pharmaceuticals and treatment of patients have also been affected due to
      changing the sources of imported medicines and raw materials for locally produced
      pharmaceuticals. Several interventions have been employed during the past few
      months in Iran to overcome the effects imposed by recent sanctions and drug
      shortages have been managed to some extent with attempts made by Iran Food and
      Drug Organization (IRI FDO). As recommended by the experts, a specific Society
      for Worldwide Interbank Financial Telecommunication line should be allocated for
      transferring money for medicines and medical devices and certain financial
      institutions are assigned for this purpose. It is also suggested that defining a
      white list of Iranian pharmaceuticals and medical device companies together with
      their foreign counterparts would facilitate this process. It appears that, in a
      public health prospective, ordinary people and patients are hurt and paying the
      cost for current sanctions. It remains the responsibility of the public health
      and international communities to separate public health from politics and to ease
      the pain of public from sanctions. 

PMID- 24329149
TI  - Preliminary identification of hemoglobin q-iran in an Iranian family from central
      province of Iran by globin chain analysis on HPLC.
AB  - Many abnormal alpha-chain hemoglobins (Hbs) are caused by single nucleotide
      mutations in alpha1- or alpha2-goblin genes. One of these Hbs is Hb Q-Iran which
      is resulted from a point mutation at codon 75 of the alpha1-globin gene (Asp
      >His). The identification of Hb Q-Iran was observed in two members of a family
      from the Central Province of Iran. In this study, Globin chain analysis on high
      performance liquid chromatography (HPLC) and DNA sequencing were applied. An
      unusual Hb variant, like HbS on alkaline pH electrophoresis was identified from
      samples of a father and his son from Arak city in the Central Province of Iran.
      The variant was further characterized by globin chain analysis and DNA sequencing
      methods. Globin chain analysis revealed an unknown globin chain peak after alpha
      globin chain peak with a different retention time from betas-globin chain, as the
      control in both samples. Genetic analysis led to the identification of an unknown
      Hb variant, Hb Q-Iran. Globin chain analysis showed the presence of an unknown
      globin chain, and likewise DNA sequencing revealed HbQ-Iran. In other words,
      Globin chain analysis procedure could preliminarily detect an unknown globin
      chain. 

PMID- 24329150
TI  - Giant adrenal pseudocyst.
AB  - Adrenal cysts are rare lesions which are usually nonfunctional and asymptomatic.
      Adrenal pseudocysts do not have epithelial linings and account for about 40% of
      adrenal cysts. We report a case of giant adrenal pseudocyst in a 32 year old
      woman presenting with flank pain who had undergone surgical excision. 

PMID- 24329151
TI  - Breakthrough discovery of HbA1c by Professor Samuel Rahbar in 1968.

PMID- 24329152
TI  - Needle-free anaesthesia, a promising option for the needle-phobic patient.

PMID- 24329153
TI  - Choosing treatment options for patients with relapsed/refractory multiple
      myeloma.
AB  - Multiple myeloma (MM) is a clonal plasma cell disorder that is still incurable
      using conventional treatments. Over the last decade, advances in front-line
      therapy have led to an increase in survival, but there are still some doubts in
      the case of relapsed/refractory disease. We searched the PubMed database for
      articles on treatment options for patients with relapsed/refractory MM published
      between 1996 and 2013. These treatments included hematopoietic cell
      transplantation (HCT), rechallenges using previous chemotherapy regimens, and
      trials of new regimens. The introduction of new agents such as the
      immunomodulatory drugs (IMIDs) thalidomide and lenalidomide, and the first-in-its
      class proteasome inhibitor bortezomib, has greatly improved clinical outcomes in
      patients with relapsed/refractory MM, but not all patients respond and those that
      do may eventually relapse or become refractory to treatment. The challenge is
      therefore to select the optimal treatment for each patient by balancing efficacy
      and toxicity. To do this, it is necessary to consider disease-related factors,
      such as the quality and duration of responses to previous therapies, and the
      aggressiveness of the relapse, and patient-related factors such as age,
      comorbidities, performance status, pre-existing toxicities and cytogenetic
      patterns. The message from the trials reviewed in this article is that the new
      agents may be used to re-treat relapsed/refractory disease, and that the
      sequencing of their administration should be modulated on the basis of the
      various disease and patient-related factors. Moreover, our understanding of the
      pharmacology and molecular action of the new drugs will contribute to the
      possibility of developing tailored treatment. 

PMID- 24329155
TI  - Water-based exercise and quality of life in women: the role of depressive
      symptoms.
AB  - Several studieshave evaluated the relation of exercise to quality of life (QoL).
      To our knowledge, no study has evaluated the relation of water-based exercise to
      depressive symptoms and QoL, or the association between improvement in QoL and
      depressive symptoms in healthy women. The purpose of this study was to evaluate
      the association of water-based exercise with changes in QoL. Forty-seven women
      performed water-based combined exercise for 12 weeks. All participants improved
      in the physical and psychological domains of QoL. Decreases in depressive
      symptoms and improvements in maximal strength and aerobic capacity were found for
      all participants. A regression model revealed that depressive symptoms were
      associated with improvements in physical and psychological domains of QoL. The
      results showed that moderate intensity, water-based exercise improved physical
      and psychological domains of QoL, depressive symptoms, aerobic capacity, and
      muscular strength of women. Furthermore, the improvement in physical and
      psychological domains of QoL appeared to be mediated by the antidepressant
      effects of exercise, but not by changes in aerobic capacity or muscular strength.

PMID- 24329156
TI  - Theoretical studies of polyatomic bimolecular reaction dynamics.
AB  - We describe recent advances in the theoretical description of bimolecular
      reactions involving four or more atoms based on quantum scattering theory and
      quasiclassical trajectory methods. The application of these methods to several
      reactions is described in detail along with relevant experimental results. The
      discussion emphasizes the use of reduced dimensionality quantum scattering
      methods and quasiclassical trajectory methods to describe quantum state-resolved
      effects, including state-specific reaction rate enhancements and product state
      distributions. Also considered are thermal rate constants, the lifetimes of
      intermediate complexes, and the branching between multiple reaction pathways. 

PMID- 24329154
TI  - The inhibition of functional expression of calcium channels by prion protein
      demonstrates competition with alpha2delta for GPI-anchoring pathways.
AB  - It has been shown recently that PrP (prion protein) and the calcium channel
      auxiliary alpha2delta subunits interact in neurons and expression systems
      [Senatore, Colleoni, Verderio, Restelli, Morini, Condliffe, Bertani, Mantovani,
      Canovi, Micotti, Forloni, Dolphin, Matteoli, Gobbi and Chiesa (2012) Neuron 74,
      300-313]. In the present study we examined whether there was an effect of PrP on
      calcium currents. We have shown that when PrP is co-expressed with calcium
      channels formed from CaV2.1/beta and alpha2delta-1 or alpha2delta-2, there is a
      consistent decrease in calcium current density. This reduction was absent when a
      PrP construct was used lacking its GPI (glycosylphosphatidylinositol) anchor. We
      have reported previously that alpha2delta subunits are able to form GPI-anchored
      proteins [Davies, Kadurin, Alvarez-Laviada, Douglas, Nieto-Rostro, Bauer, Pratt
      and Dolphin (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 1654-1659] and show further
      evidence in the present paper. We have characterized recently a C-terminally
      truncated alpha2delta-1 construct, alpha2delta-1DeltaC, and found that, despite
      loss of its membrane anchor, it still shows a partial ability to increase calcium
      currents [Kadurin, Alvarez-Laviada, Ng, Walker-Gray, D'Arco, Fadel, Pratt and
      Dolphin (2012) J. Biol. Chem. 1287, 33554-33566]. We now find that PrP does not
      inhibit CaV2.1/beta currents formed with alpha2delta-1DeltaC, rather than
      alpha2delta-1. It is possible that PrP and alpha2delta-1 compete for GPI-anchor
      intermediates or trafficking pathways, or that interaction between PrP and
      alpha2delta-1 requires association in cholesterol-rich membrane microdomains. Our
      additional finding that CaV2.1/beta1b/alpha2delta-1 currents were inhibited by
      GPI-GFP, but not cytosolic GFP, indicates that competition for limited GPI-anchor
      intermediates or trafficking pathways may be involved in PrP suppression of
      alpha2delta subunit function. 

PMID- 24329157
TI  - Approaches for high-throughput pharmacokinetic screening of low-molecular-weight
      drug candidates.
AB  - In the face of advancing technology in combinatorial synthesis and high
      throughput screening, the drug discovery process continues to evolve. Drug
      metabolism and pharmacokinetics (DMPK) studies play a key role in lead
      identification and optimization. This fast-paced development process has imposed
      an enormous burden on the analytical chemist to design faster and more sensitive
      assay techniques to aid the drug discovery and development. Various strategies
      aimed at increasing the throughput and reducing sample numbers in discovery DMPK
      have been developed for both in vitro and in vivo experiments. However, quantity
      and speed, often associated with technology development, do not always guarantee
      quality but a clear strategic focus in the spirit of 'Fit for Purpose' approach
      is required to implement systems to generate high-quality data and to drive
      research in new directions. 

PMID- 24329158
TI  - Lack of physician-patient communication as a key factor associated with
      malpractice litigation in neonatal brachial plexus palsy.
AB  - OBJECT: Perinatal disorders are prone to malpractice litigation. Neonatal
      brachial plexus palsy (NBPP) results from stretching the nerves in the perinatal
      period and may lead to paresis or paralysis and sensory loss in the affected arm.
      Little is known about the key factors associated with malpractice litigation by
      families of patients with NBPP and whether these factors reflect the practice
      environment or are inherent to the condition. In this study, the authors
      documented the percentage of families of NBPP patients at a specialty center that
      had filed a malpractice suit and described the key factors associated with that
      pursuit of legal action. METHODS: The families/caregivers of 51 patients with
      NBPP who had presented to the University of Michigan Interdisciplinary Brachial
      Plexus Program participated in this study. A qualitative research design was
      applied using both a questionnaire to examine psychosocial factors and a dynamic
      tool to measure health outcomes from the patient perspective via parent proxy
      (Patient-Reported Outcomes Measurement Information System [PROMIS] assessment
      instruments). Statistical analysis included the Fisher exact test, chi-square
      test, and Student t-test. The study protocol was approved by the University of
      Michigan institutional review board. RESULTS: Forty-seven percent of the families
      pursued malpractice litigation. In comparing patient families that had pursued
      legal action with those that had not, significant differences were revealed in
      the perception that the sustained birth injury was unnecessary (p = 0.002), the
      information received in the perinatal period was inadequate (p = 0.003), family
      concerns were ignored in the perinatal period (p = 0.005), and family concerns
      were not adequately addressed (p < 0.001). Sixty-six percent of the families
      received external advice to pursue legal action. The PROMIS survey revealed
      significant group differences in depressive symptoms (p = 0.008), fatigue (p =
      0.02), pain (p = 0.01), and anger (p = 0.004). In contrast, the extent of NBPP
      was not associated with malpractice litigation (p = 0.18). Age, sex, and race
      were not significantly different between litigation and nonlitigation groups.
      CONCLUSIONS: Physician-controllable factors, such as communication in the
      perinatal period, are associated with malpractice litigation in NBPP. The
      perceived level of global disability may affect the pursuit of malpractice
      litigation, whereas the isolated extent of nerve root involvement and/or upper
      extremity dysfunction are not significant factors in pursuing litigation.
      Identifying and ameliorating these factors within the practice environment may
      decrease the animosity between families and health care providers and improve
      overall outcome for patients with NBPP.

PMID- 24329159
TI  - Intracranial calcified pseudocyst reaction to a shunt catheter.
AB  - A 9-year-old boy with spina bifida, Chiari II malformation, and hydrocephalus
      presented with signs of increased intracranial pressure consistent with a shunt
      malfunction. Radiological investigations revealed an intracranial calcified
      lesion along the ventricular catheter. A shunt tap revealed a translucent milky
      white fluid. The patient underwent a ventriculostomy and, eventually, a shunt
      revision. Pathology findings were consistent with the formation of dystrophic
      calcification and a pseudocyst around the shunt catheter. Postoperatively, the
      patient returned to his neurological baseline. This is, to the best of the
      authors' knowledge, the first report of an intracranial calcified pseudocyst in a
      patient with normal renal function. 

PMID- 24329160
TI  - Neurolysis alone as the treatment for neuroma-in-continuity with more than 50%
      conduction in infants with upper trunk brachial plexus birth palsy.
AB  - OBJECT: The debate addressed in this article is that of surgical treatment
      methods for a neuroma-in-continuity. The authors of this study chose to test the
      hypothesis that more severe nerve injuries, as distinguished by < 50% conduction
      across a neuroma-in-continuity, could be treated with neuroma resection and
      grafting, whereas less severe nerve injuries, with > 50% conduction across the
      neuroma, could be treated with neurolysis alone. METHODS: The goal of this study
      was to compare preoperative and postoperative Active Movement Scale (AMS) scores
      in children with upper trunk brachial plexus birth injuries treated with
      neurolysis alone if the neuroma's conductivity was > 50% on intraoperative nerve
      testing. Seventeen patients (7 male, 10 female) met the criteria for inclusion in
      this study. Surgery was done when the patients were an average of 10 months old
      (range 6-19 months). The authors analyzed AMS scores from the preoperative
      assessment, 1-year postoperative follow-up visit, and subsequent follow-up
      assessment as close to 3 years after surgery as possible (referred to in this
      paper as > 2-year postoperative scores). RESULTS: Comparison of preoperative and
      1-year follow-up data showed significant improvement in shoulder abduction,
      flexion, external rotation, and internal rotation; elbow flexion and supination;
      and wrist extension. Comparison of preoperative findings and results of
      assessment at > 2-year follow-up showed significant improvement in shoulder
      abduction, flexion, external rotation; and elbow flexion and supination. At final
      follow-up, useful function (AMS score of 6 or 7) was achieved for elbow flexion
      in 14 of 16 patients, shoulder flexion in 11 of 15 patients, shoulder abduction
      in 11 of 16 patients, and shoulder external rotation in 5 of 15 patients.
      CONCLUSIONS: This report indicates that there is a subgroup of patients who can
      benefit clinically, with functional improvement of shoulder and elbow function,
      from treatment with neurolysis alone for upper trunk lesions demonstrating more
      than 50% conduction across the neuroma on intraoperative nerve testing. Patients
      with less than 50% conduction, indicating more severe disease, are treated with
      nerve resection and grafting in the authors' treatment algorithm.

PMID- 24329161
TI  - Cerebrospinal fluid white blood cell counts in infants with myelomeningoceles.
AB  - OBJECT: The authors undertook this study to determine white blood cell (WBC)
      counts in CSF obtained from lateral ventricles and myelomeningoceles (MMCs) in
      infants in a developing country at the time of their initial presentation for
      medical evaluation. METHODS: CSF was aspirated from the lateral ventricles and
      from MMC sacs of 100 consecutive infants at Kijabe Hospital, Kijabe, Kenya.
      Peripheral blood WBC counts and CSF WBC counts were determined in the laboratory.
      CSF with WBC counts of 5 cells/mm(3) or greater was cultured. RESULTS: The mean
      WBC count in ventricular CSF was 16 cells/mm(3), with a median and mode of 0
      cells/mm(3). The mean WBC count of CSF in MMC sacs was 141 cells/mm(3) (median 15
      cells/mm(3)). No child had both a positive culture from ventricular CSF and a
      negative culture from MMC CSF. There was no correlation between age at
      presentation and WBC counts in the MMCs. Infants younger than 8 days old were as
      likely to have high WBC counts in CSF from their MMC sacs as were older children;
      7 of 12 infants with 500 WBCs or more in CSF from their MMCs were younger than 8
      days old. Only 5 of 58 CSF specimens from MMC sacs with 5 or more WBCs/mm(3) had
      positive bacterial cultures, which may be a reflection of CSF specimen processing
      rather than of true culture negativity. CONCLUSIONS: CSF from ventricular fluid
      of infants presenting with MMCs infrequently has high WBC counts, so infrequently
      that it does not need to be evaluated routinely. CSF in MMC sacs often has high
      WBC counts that suggest the presence of bacterial infection. In developing
      countries where culture reliability is questionable, intravenous administration
      of antibiotics before MMC closure for infants with high MMC WBC counts may
      diminish postoperative meningitis/ventriculitis.

PMID- 24329162
TI  - Determination of acetamiprid and IM-1-2 in postmortem human blood, liver, stomach
      contents by HPLC-DAD.
AB  - An HPLC-DAD method was developed to detect and quantify a neonicotinoid
      insecticide acetamiprid (ATP) and its metabolite IM-1-2 in autopsy samples of a
      fatal intoxication case. The postmortem blood and tissue distribution of ATP and
      IM-1-2 was determined for the first time. The method showed acceptable precisions
      and recoveries with relative standard deviations of <10% for ATP level and 1.38 %
      for IM-1-2. The detection and quantification limits for ATP were 0.015 MUg/mL and
      0.030 MUg/mL for blood and were 0.035 MUg/g and 0.050 MUg/g for liver samples,
      respectively. The mean contents of ATP were 0.79 MUg/g in the liver, 47.35 MUg/g
      in the stomach contents and 2.7 MUg/mL in the blood. IM-1-2 content was 17.0
      MUg/g in the stomach contents. ATP and IM-1-2 were not detected in the urine. The
      presence of ATP and IM-1-2 in the samples was confirmed by GC-MS. The method can
      be exploited in future forensic casework.

PMID- 24329163
TI  - Assessment of the ability of the Privigen(r) purification process to deplete
      thrombogenic factor XIa from plasma.
AB  - BACKGROUND AND OBJECTIVES: Activated clotting factor FXI (FXIa) has been
      postulated to play a significant role in thromboembolic events potentially
      associated with the administration of intravenous immunoglobulin. The purpose of
      this study was to demonstrate that thrombogenic agents, in particular FXIa and
      FXI, are depleted or inactivated in Privigen((r)) . MATERIALS AND METHODS: The
      ability of the purification process to deplete FXIa from plasma was studied. All
      steps of the Privigen((r)) production were investigated for potential activation
      of FXI to FXIa with spiking experiments. RESULTS: Privigen((r)) contains no
      procoagulant activity as determined by FXIa chromogenic assay, non-activated
      partial thromboplastin time (NaPTT) and thrombin generation assays (TGA, FXIa
      like activity). The coagulation times were >200 s in the NaPTT test. FXIa was
      below the detection limit of 0.14 ng/ml (chromogenic assay) and below the
      quantification limit of 0.2 ng/ml (TGA). FXIa spiking experiments showed that the
      analytical methods used can detect traces of procoagulant activity in
      immunoglobulin samples. FXIa spiking and kinetic experiments during the octanoic
      acid fractionation step showed that a substantial reduction in FXIa specific
      activity (by >=99.9% within 40 min of octanoic acid incubation) was reached
      already at an early stage of the manufacturing process. These results were
      confirmed in vivo: in a modified Wessler test, no thrombus was reported.
      CONCLUSION: The Privigen((r)) manufacturing process has the capability to remove
      thrombogenic factors: octanoic acid precipitation, designed to remove a variety
      of contaminants during immunoglobulin purification, also removes almost all FXIa
      from plasma and further purification steps do not activate FXI.

PMID- 24329164
TI  - The formulation, chemical and physical characterisation of clarithromycin-based
      macrolide solution pressurised metered dose inhaler.
AB  - OBJECTIVES: The formulation of a clarithromycin (CLA) pressurised metered dose
      inhalers (pMDIs) solution formulation opens up exciting therapeutic opportunities
      for the treatment of inflammation in chronic obstructive lung diseases. In this
      study, we have formulated and tested a low dose macrolide formulation of CLA for
      treatment of inflammation and studied its physicochemical and aerosol properties.
      METHODS: The system was characterised for in-vitro aerosol performance using an
      Andersen cascade impactor. Short-term chemical and physical stability was
      assessed by dose content uniformity over a range of temperatures. Standard
      physicochemical characteristics were also investigated using scanning electron
      microscopy, thermo analysis and laser diffraction techniques. KEY FINDINGS: The
      formulation had a relatively high fine particle fraction (47%) and produced a
      particle size distribution suitable for inhalation drug delivery. Particles had
      an irregular morphology and were predominately amorphous. Furthermore, the short
      term stability showed the formulation to be stable from 4 to 37 degrees C.
      CONCLUSIONS: This study demonstrated the feasibility of formulating a solution
      based pMDI containing CLA for the treatment of lung inflammatory diseases.

PMID- 24329165
TI  - Enzymatic cleaning of biofouled thin-film composite reverse osmosis (RO) membrane
      operated in a biofilm membrane reactor.
AB  - Application of environmentally friendly enzymes to remove thin-film composite
      (TFC) reverse osmosis (RO) membrane biofoulants without changing the physico
      chemical properties of the RO surface is a challenging and new concept. Eight
      enzymes from Novozyme A/S were tested using a commercially available biofouling
      resistant TFC polyamide RO membrane (BW30, FilmTech Corporation, Dow Chemical
      Co.) without filtration in a rotating disk reactor system operated for 58 days.
      At the end of the operation, the accumulated biofoulants on the TFC RO surfaces
      were treated with the three best enzymes, Subtilisin protease and lipase;
      dextranase; and polygalacturonase (PG) based enzymes, at neutral pH (~7) and
      doses of 50, 100, and 150 ppm. Contact times were 18 and 36 h. Live/dead
      staining, epifluorescence microscopy measurements, and 5 MUm thick cryo-sections
      of enzyme and physically treated biofouled membranes revealed that Subtilisin
      protease- and lipase-based enzymes at 100 ppm and 18 h contact time were optimal
      for removing most of the cells and proteins from the RO surface. Culturable cells
      inside the biofilm declined by more than five logs even at the lower dose (50
      ppm) and shorter incubation period (18 h). Subtilisin protease- and lipase-based
      enzyme cleaning at 100 ppm and for 18 h contact time restored the hydrophobicity
      of the TFC RO surface to its virgin condition while physical cleaning alone
      resulted in a 50 degrees  increase in hydrophobicity. Moreover, at this optimum
      working condition, the Subtilisin protease- and lipase-based enzyme treatment of
      biofouled RO surface also restored the surface roughness measured with atomic
      force microscopy and the mass percentage of the chemical compositions on the TFC
      surface estimated with X-ray photoelectron spectroscopy to its virgin condition.
      This novel study will encourage the further development and application of
      enzymes to remove biofoulants on the RO surface without changing its surface
      properties.

PMID- 24329166
TI  - Health security resolutions for 2014.

PMID- 24329167
TI  - Ready or not: analysis of a no-notice mass vaccination field response in
      Philadelphia.
AB  - Local health departments typically rely on exercises to test preparedness
      capacity; however, pre-scripted drills often lack the sense of urgency that a
      real event would engender. No-notice, unscripted exercises that challenge staff
      to think critically under pressure may provide a mechanism for a more realistic
      assessment of preparedness capacity. The very active influenza season of 2012-13
      presented the Public Health Preparedness Program at the Philadelphia Department
      of Public Health with the opportunity to conduct an influenza vaccination clinic
      at a local boarding school. Program leaders used this opportunity to design a no
      notice exercise to test the ability of staff to effectively coordinate an
      emergency field response while simultaneously delivering a real public health
      intervention. On the day of the exercise, staff members were given 6 hours to
      plan and execute a vaccination clinic without any guidance from program leaders.
      Best practices observed during the exercise included: (1) early identification
      and mitigation of rate-limiting steps, and (2) successful implementation of a
      previously untested high-throughput vaccination model. Although the primary
      intent of the exercise was to assess the ability of staff to respond to a no
      notice event, this vaccination clinic also functioned as a microcosm of a larger
      response, revealing several considerations related to vaccine ordering, staff
      resources, and throughput rates that have broader implications for public health
      responses to large-scale biological attacks or pandemics. 

PMID- 24329168
TI  - A critical analysis of Peru's HIV grant proposals to the Global Fund.
AB  - Peru has applied to six of the Global Fund to Fight AIDS, Tuberculosis and
      Malaria (the Global Fund) rounds for funding, achieving success on four
      occasions. The process of proposal development has, however, been criticised,
      especially concerning the use of evidence, relevance/consistency and performance
      indicators. We aimed to analyse the Peruvian Global Fund proposals according to
      those dimensions, providing feedback to improve future local efforts and inform
      global discussions around Global Fund procedures. We analysed the content of four
      HIV-focused proposals (rounds 2, 5, 6 and 8) regarding epidemic context, needs
      identification and prioritisation and monitoring and evaluation systems. Peruvian
      proposals submitted after round 1 were described as resulting from collaborative
      inputs involving formerly unrepresented sectors, principally 'vulnerable
      populations'. However, difficulties arose regarding the amount and quality of
      evidence about the epidemiological context; limited consideration of social
      determinants of the epidemic; lack of theory-driven interventions, and little
      synergy across projects and the inclusion of weak monitoring and evaluation
      systems, with poor indicators and measurement procedures. Prioritising the
      development of analytical and technical skills to generate Global Fund proposals
      would enhance the country's capacity to produce and utilise evidence, improve the
      technical-political interface, strengthen information systems and lead to more
      informed decision making and accountability. 

PMID- 24329170
TI  - Patient Attachment to Therapist Rating Scale: development and psychometric
      properties.
AB  - OBJECTIVE: To report on the development and initial psychometric properties of a
      new rating scale for patent-therapist attachment. METHOD: Seventy interviews from
      the Young Adult Psychotherapy Project (YAPP) were rated. RESULTS: Excellent
      internal consistency (Cronbach's alpha > .90) was observed for all four subscales
      (Security, Deactivation, Hyperactivation, and Disorganization). Three subscales
      showed good inter-rater reliability (ICC > .60), while one (Hyperactivation) had
      poor (ICC < .40). Correlations with measures of alliance, mental representations,
      and symptom distress support the construct validity of the reliable subscales.
      Exploratory factor analysis indicated three underlying factors explaining 82% of
      the variance. CONCLUSIONS: The Patient Attachment to Therapist Rating Scale is a
      promising approach for assessing the quality of attachment to therapist from
      patient narratives. Future development should focus on improving the
      discrimination of the insecure subscales.

PMID- 24329171
TI  - Herbivore cues from the fall armyworm (Spodoptera frugiperda) larvae trigger
      direct defenses in maize.
AB  - In addition to feeding damage, herbivores release cues that are recognized by
      plants to elicit defenses. Caterpillar oral secretions have been shown to trigger
      herbivore defense responses in several different plant species. In this study,
      the effects of two fall armyworm (Spodoptera frugiperda) oral secretions (saliva
      and regurgitant) on caterpillar defense responses in maize (Zea mays) were
      examined. Only minute amounts of regurgitant were deposited on the maize leaf
      during larval feeding bouts and its application to leaves failed to induce the
      expression of several herbivore defense genes. On the other hand, caterpillars
      consistently deposited saliva on leaves during feeding and the expression of
      several maize defense genes significantly increased in response to saliva
      application and larval feeding. However, feeding by ablated caterpillars with
      impaired salivation did not induce these defenses. Furthermore, bioassays
      indicated that feeding by unablated caterpillars significantly enhanced defenses
      when compared with that of ablated caterpillars. Another critical finding was
      that the maize genotype and stage of development affected the expression of
      defense genes in response to wounding and regurgitant treatments. These results
      demonstrate that fall armyworm saliva contains elicitors that trigger herbivore
      defenses in maize. 

PMID- 24329172
TI  - Substitutions of two amino acids in the nucleotide-binding site domain of a
      resistance protein enhance the hypersensitive response and enlarge the PM3F
      resistance spectrum in wheat.
AB  - Proteins with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains
      are major components of the plant immune system. They usually mediate resistance
      against a subgroup of races of a specific pathogen. For the allelic series of the
      wheat powdery mildew resistance gene Pm3, alleles with a broad and a narrow
      resistance spectrum have been described. Here, we show that a broad Pm3 spectrum
      range correlates with a fast and intense hypersensitive response (HR) in a
      Nicotiana transient-expression system and this activity can be attributed to two
      particular amino acids in the ARC2 subdomain of the NBS. The combined
      substitution of these amino acids in narrow-spectrum PM3 proteins enhances their
      capacity to induce an HR in Nicotiana benthamiana, and we demonstrate that these
      substitutions also enlarge the resistance spectrum of the Pm3f allele in wheat.
      Finally, using Bph14, we show that the region carrying the relevant amino acids
      also plays a role in the HR regulation of another coiled-coil NBS-LRR resistance
      protein. These results highlight the importance of an optimized NBS-'molecular
      switch' for the conversion of initial pathogen perception by the LRR into
      resistance-protein activation, and we describe a possible approach to extend the
      effectiveness of resistance genes via minimal targeted modifications in the NBS
      domain.

PMID- 24329173
TI  - Translocation and functional analysis of Pseudomonas savastanoi pv. savastanoi
      NCPPB 3335 type III secretion system effectors reveals two novel effector
      families of the Pseudomonas syringae complex.
AB  - Pseudomonas savastanoi pv. savastanoi NCPPB 3335 causes olive knot disease and is
      a model pathogen for exploring bacterial infection of woody hosts. The type III
      secretion system (T3SS) effector repertoire of this strain includes 31 effector
      candidates plus two novel candidates identified in this study which have not been
      reported to translocate into plant cells. In this work, we demonstrate the
      delivery of seven NCPPB 3335 effectors into Nicotiana tabacum leaves, including
      three proteins from two novel families of the P. syringae complex effector super
      repertoire (HopBK and HopBL), one of which comprises two proteins (HopBL1 and
      HopBL2) that harbor a SUMO protease domain. When delivered by P. fluorescens
      heterologously expressing a P. syringae T3SS, all seven effectors were found to
      suppress the production of defense-associated reactive oxygen species. Moreover,
      six of these effectors, including the truncated versions of HopAA1 and HopAZ1
      encoded by NCPPB 3335, suppressed callose deposition. The expression of HopAZ1
      and HopBL1 by functionally effectorless P. syringae pv. tomato DC3000D28E
      inhibited the hypersensitive response in tobacco and, additionally, expression of
      HopBL2 by this strain significantly increased its competitiveness in N.
      benthamiana. DNA sequences encoding HopBL1 and HopBL2 were uniquely detected in a
      collection of 31 P. savastanoi pv. savastanoi strains and other P. syringae
      strains isolated from woody hosts, suggesting a relevant role of these two
      effectors in bacterial interactions with olive and other woody plants. 

PMID- 24329174
TI  - Alternative cell death mechanisms determine epidermal resistance in incompatible
      barley-Ustilago interactions.
AB  - Programmed cell death is a key feature of epidermal plant immunity, which is
      particularly effective against biotrophic microbes that depend on living host
      tissue. The covered smut fungus Ustilago hordei establishes a compatible
      biotrophic interaction with its host plant barley. The maize smut U. maydis
      triggers a nonhost response in barley, which results in epidermal cell death.
      Similarly, Ustilago mutants being deleted for pep1, a gene encoding a secreted
      effector, are blocked upon host penetration. We studied the epidermal responses
      of barley to incompatible Ustilago strains. Molecular and cellular analyses were
      used to test the impact of Bax inhibitor-1 (BI-1), a suppressor of programmed
      cell death, on the barley nonhost resistance to U. maydis as well as Ustilago
      Deltapep1 mutants. Overexpression of BI-1 resulted in partial break of barley
      nonhost resistance to U. maydis. By contrast, the epidermal cell death response
      triggered by pep1 deletion mutants was not impaired by BI-1. Hypersensitive
      response-like cell death caused by U. maydis wild-type infection showed features
      of necrotic cell death, while Deltapep1 mutant-induced host responses involved
      hallmarks of autophagy. Therefore, we propose that the mechanisms of epidermal
      cell death in response to different types of incompatible pathogens depend on
      spatial and temporal appearance of cell-death-triggering stimuli. 

PMID- 24329175
TI  - Callyspongiolide, a cytotoxic macrolide from the marine sponge Callyspongia sp.
AB  - A novel macrolide, callyspongiolide, whose structure was determined by
      comprehensive analysis of the NMR and HRMS spectra, was isolated from the marine
      sponge Callyspongia sp. collected in Indonesia. The compound features a carbamate
      substituted 14-membered macrocyclic lactone ring with a conjugated structurally
      unprecedented diene-ynic side chain terminating at a brominated benzene ring.
      Callyspongiolide showed strong cytotoxicity against human Jurkat J16 T and Ramos
      B lymphocytes. 

PMID- 24329176
TI  - Prevalence of oral and systemic manifestations in pediatric HIV cohorts with and
      without drug therapy.
AB  - The prevalence of orofacial and systemic manifestations and their association
      with drug therapy in pediatric HIV patients is scarce in the literature. The aim
      of the study was to determine the prevalence of oro-facial and systemic
      manifestations in HIV sero-positive children with and without highly active
      antiretroviral therapy (HAART). The study population consisted of 100 pediatric
      HIV patients (n=47 on HAART and n=53 not on HAART). The majority of the children
      (n=56) had at least one or more oro-facial manifestation associated with HIV.
      Oral candidiasis was the most common oral finding present in the HAART (14/33)
      and non-HAART groups (19/33). Recurrent aphthous ulcers was the only significant
      oral finding, present more in the HAART group. The percentage of children with
      upper respiratory tract infection was also more in the HAART group. The other
      lesions which were found to be significant were seborrheic dermatitis, pulmonary
      tuberculosis and otitis media. There was no significant difference in the
      participants' oral findings based on CD4 counts in the HAART and non- HAART
      groups. The prevalence of oral and systemic manifestations is a persistent
      feature associated with pediatric HIV, though of moderate intensity in those
      using HAART and may vary according to individual immune status. 

PMID- 24329177
TI  - Methanobrevibacter smithii archaeosomes-entrapped mzNL4-3 virus-like particles
      induce specific T helper 1-oriented cellular and humoral responses against HIV-1.
AB  - Despite numerous and tremendous achievements in the development and
      standardization of HIV vaccines, there are still lots of vague concepts in HIV
      vaccinology. Various approaches have been applied to design an efficient HIV
      vaccine. Due to their lack of replication ability and expression of native
      antigens at the same time virus-like particles, such as previously introduced
      mzNL4-3 HIV-1 VLPs are among the highlighted candidates in this field. On the
      other part, application of adjuvants is an inseparable strategy in the vaccine
      development researches. Archaeosomes are liposomal adjuvants with intensifiying
      features of T helper 1 and cytotoxic T-cells responses. Archaeosomes derived from
      Methanobrevibacter smithii has been shown to enhance MHC class I-dependent
      antigen presentation and hence, are to be advantageous in the development of
      vaccines against viral infections. Herein, we have studied efficiency of mzNL4-3
      VLPs entrapped in M. smithii archaeosomes as an HIV-1 vaccine candidate to induce
      humoral and cellular responses in BALB/c mice. Analysis of total and subtype
      specific anti-Env IgG antibody, as well as, cytokine secretion pattern revealed
      an efficient promotion of anti-HIV specific T helper 1 responses in immunized
      animals. This finding was evidenced by the significant dominance of IgG2a subtype
      in the sera and considerable secretion of IFN-gamma by specifically induced
      splenocytes of mice immunized with VLP-containing archaeosomes (VLP+
      Archaeosome). In addition, ELISpot assay verified these results and indicated the
      significantly higher frequency of IFN-gamma secreting splenocytes in immunized
      models. The ratio of IFN-gamma to IL-4 spot forming cells (SFCs) in the VLP+
      Archaeosome immunized mice was also higher than that of the other groups
      immunized with either VLP-free archaeosomes or VLPs formulated with
      complete/incomplete Freund's adjuvants. These results propound M. smithii
      archaeosomes-entrapped mzNL4-3 VLPs as a promising immunogen which specifically
      induces and augments T-helper 1 oriented responses against HIV antigens. 

PMID- 24329178
TI  - Drug approval and drug effectiveness.
AB  - Data on the efficacy and safety of psychiatric medicines should form the
      foundation of evidence-based treatment practices. The US Food and Drug
      Administration (FDA) reviews such data in determining whether to approve new
      treatments, and the published literature serves as a repository for evidence on
      treatment benefits and harms. We describe the FDA review of clinical trials,
      examining the underlying logic and legal guidelines. Several FDA reviews provide
      evidence that the agency requires only minimal efficacy for psychiatric drugs.
      Further, in some instances, the FDA has relied on secondary rather than primary
      outcomes and has discounted the findings of negative studies in its review of
      antidepressant and antipsychotic medications. The published literature provides
      another lens into the safety and efficacy of treatments. We describe how
      treatment efficacy is systematically overstated and treatment-related harms are
      understated in the scientific literature. Suggestions are provided to improve
      public access to underlying safety and efficacy data and for the FDA to
      potentially improve its review process. 

PMID- 24329179
TI  - The role of the DSM-5 personality trait model in moving toward a quantitative and
      empirically based approach to classifying personality and psychopathology.
AB  - The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-5) represents a watershed moment in the history of official psychopathology
      classification systems because it is the first DSM to feature an empirically
      based model of maladaptive personality traits. Attributes of patients with
      personality disorders were discussed by the DSM-5 Personality and Personality
      Disorders Work Group and then operationalized and refined in the course of an
      empirical project that eventuated in the construction of the Personality
      Inventory for DSM-5 (PID-5). We review research to date on the DSM-5 trait model,
      with a primary aim of discussing how this kind of research could serve to better
      tether the DSM to data as it continues to evolve. For example, studies to date
      suggest that the DSM-5 trait model provides reasonable coverage of personality
      pathology but also suggest areas for continued refinement. This kind of research
      provides a way of evolving psychopathology classification on the basis of
      research evidence as opposed to clinical authority. 

PMID- 24329180
TI  - From Kanner to DSM-5: autism as an evolving diagnostic concept.
AB  - Seven decades have elapsed since Leo Kanner described the syndrome he termed
      early infantile autism. Over this time, and particularly over the past two
      decades, noteworthy changes have occurred in how the condition is conceptualized.
      Here we provide an overview of these changes, beginning with a brief discussion
      of the significance of classification in general before discussing Kanner's
      original paper and subsequent changes. We touch on relevant issues, such as
      comorbidity, dimensional aspects of diagnosis and screening, and the complex
      issue of diagnosis relative to eligibility for services. Approaches to diagnosis
      have tended to swing from emphasizing overarching groups (lumping) to focusing on
      potentially distinct subgroups (splitting). Autism raises particular problems
      given the broad range of syndrome expression over age and developmental level.
      The most recent revision of the American Psychiatric Association's diagnostic
      taxonomy marks a significant departure from its predecessor and has been the
      focus of much debate. It remains unclear which of the currently existing
      categorical approaches will ultimately be most widely applied. We hope to convey
      a sense of areas in which consensus has been achieved and areas of continued
      controversy. 

PMID- 24329181
TI  - The influence of daily routines on engaging in diabetes self-management.
AB  - OBJECTIVE: In contrast to previous research concerning the importance of routines
      in occupational engagement, most of which have largely focused on the routines of
      children and families, in this study a qualitative methodology was used to
      understand how routines function in a specific occupation: diabetes self
      management (DSM). METHODS: Ten low-income women participated in a multiple
      methods study that involved completing a time-geographic diary (TGD) and
      participating in a TGD interview. RESULTS: Findings reveal that pre-existing
      routines must be changed so that they may better support engagement in DSM, and
      that such changes are tied to underlying habits and life situations. The
      experiences of study participants also showed that the distribution of daily
      occupations through time and across social spheres can be both supportive of and
      problematic for engaging in DSM. In addition, the structure and sequence of
      competing daily occupations influences the available time and opportunities for
      people to further develop their skills and become more adept self-managers.
      CONCLUSIONS: The implications of these findings for occupational science and
      therapy are discussed.

PMID- 24329182
TI  - Real-time atomic scale imaging of nanostructural evolution in aluminum alloys.
AB  - We present a new approach to study the three-dimensional compositional and
      structural evolution of metal alloys during heat treatments such as commonly used
      for improving overall material properties. It relies on in situ heating in a high
      resolution scanning transmission electron microscope (STEM). The approach is
      demonstrated using a commercial Al alloy AA2024 at 100-240  degrees C, showing in
      unparalleled detail where and how precipitates nucleate, grow, or dissolve. The
      observed size evolution of individual precipitates enables a separation between
      nucleation and growth phenomena, necessary for the development of refined growth
      models. We conclude that the in situ heating STEM approach opens a route to a
      much faster determination of the interplay between local compositions, heat
      treatments, microstructure, and mechanical properties of new alloys. 

PMID- 24329183
TI  - Associations between prenatal nicotine exposure, oxidative stress, and postpartum
      visceral fat.
AB  - This study aimed to examine the associations among prenatal nicotine exposure,
      oxidative stress, and postpartum visceral fat among women exposed to secondhand
      smoke (SHS). The study was conducted in Kelantan, Malaysia, from April 2010 to
      December 2012. Blood samples were collected in the second and third trimesters
      from 135 healthy pregnant women who were followed-up at delivery, 2 months, 6
      months and 12 months postpartum. Maternal hair nicotine and oxidative stress
      markers during pregnancy were measured. Visceral fat was assessed by
      bioelectrical impedance. Multiple linear regression analysis revealed that
      maternal hair nicotine concentration was associated with increased DNA damage
      (tail moment: beta=0.580, p=0.001) and decreased glutathione peroxidase (beta=
      12.100; p=0.009) in the second trimester of pregnancy. Increased DNA damage,
      protein oxidation and total antioxidant capacity in the second trimester were
      associated with 2, 6, and 12 months postpartum visceral fat. No direct
      association was found between prenatal hair nicotine level and postpartum
      visceral fat; however, these results suggest that any relation of SHS to visceral
      adiposity may be indirect, mediated via enhanced oxidative stress.

PMID- 24329184
TI  - Delivering pharmacogenetic testing to the masses: an achievable goal?

PMID- 24329186
TI  - Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir
      pharmacokinetics.
AB  - AIM: To evaluate potential pharmacogenetic effects of UGT1A1 polymorphisms on the
      pharmacokinetics (PK) of dolutegravir (Tivicay(r); ViiV Healthcare, NC, USA), an
      HIV-1 integrase inhibitor. PATIENTS & METHODS: Analysis of pooled data from nine
      Phase I and II clinical studies was undertaken for 89 subjects receiving repeat
      dolutegravir 50 mg once daily (tablet formulation) who were genotyped for known
      UGT1A1 functional variants. RESULTS: Geometric mean ratio (92% CI) for subjects
      carrying low (*28/*28 and *28/*37) and reduced activity (*1/*6, *1/*28, *1/*37,
      *28/*36 and *36/*37) polymorphisms compared with subjects with normal activity
      (*1/*1 and *1/*36) showed decreased oral clearance (CL/F; 0.765 [92% CI: 0.659
      0.889]), increased area under the concentration-time curve (AUC(0-tau); 1.307
      [1.125-1.518]) and C(max) (1.221 [1.063-1.402]), respectively. CONCLUSION:
      Increased dolutegravir exposure in carriers of UGT1A1 reduced function
      polymorphisms is not clinically significant based on accumulated safety data so
      dose adjustment in these individuals is not required.

PMID- 24329187
TI  - Effect of CYP2D6 on risperidone pharmacokinetics and extrapyramidal symptoms in
      healthy volunteers: results from a pharmacogenetic clinical trial.
AB  - AIM: To elucidate the relationship between CYP2D6 genotype and risperidone
      pharmacokinetics and extrapyramidal symptoms we propose the APSEP pharmacogenetic
      clinical trial. MATERIALS & METHODS: Twenty-five healthy subjects were included
      in this randomized, placebo-controlled, single dose (risperidone 2.5 mg)
      crossover and double-blind clinical trial. Subjects were selected according to
      their CYP2D6 genotype and classified as: poor metabolizers (n = 8), extensive
      metabolizers (n = 10) and ultrarapid metabolizers (n = 7). RESULTS & CONCLUSION:
      Our study demonstrates that CYP2D6 predicted 65% of the risperidone metabolism
      variability. Moreover, its ability to predict actigraphy records is similar to
      the predictive power of pharmacokinetic parameters (24%). Our results also
      highlight the need for the development of pharmacogenetic predictors that take
      into account the complexity of pharmacokinetic and pharmacodynamic relationships.

PMID- 24329188
TI  - Prediction of optimal warfarin maintenance dose using advanced artificial neural
      networks.
AB  - BACKGROUND: In recent years, pharmacogenetic algorithms were developed for
      estimating the appropriate dose of vitamin K antagonists. AIM: To evaluate the
      performance of new generation artificial neural networks (ANNs) to predict the
      warfarin maintenance dose. METHODS: Demographic, clinical and genetic data
      (CYP2C9 and VKORC1 polymorphisms) from 377 patients treated with warfarin were
      used. The final prediction model was based on 23 variables selected by TWIST(r)
      system within a bipartite division of the data set (training and testing)
      protocol. RESULTS: The ANN algorithm reached high accuracy, with an average
      absolute error of 5.7 mg of the warfarin maintenance dose. In the subset of
      patients requiring <=21 mg and 21-49 mg (45 and 51% of the cohort, respectively)
      the absolute error was 3.86 mg and 5.45 with a high percentage of subjects being
      correctly identified (71 and 73%, respectively). CONCLUSION: ANN appears to be a
      promising tool for vitamin K antagonist maintenance dose prediction.

PMID- 24329189
TI  - Pharmacogenomics primer course for first professional year pharmacy students.
AB  - BACKGROUND: The importance of pharmacogenomics (PGx) is widely recognized in
      healthcare; however, PGx knowledge and confidence is lacking among many
      healthcare professionals. Pharmacists are the most logical PGx experts, yet most
      pharmacy schools do not require the basic science foundations of PGx as admission
      prerequisites. METHODS: A PGx primer course was developed for first year pharmacy
      students. In addition to genomics-based didactic material, this course also
      contains 'journaling' exercises and a group term paper based on a self
      genotyping/phenotype exercise. The effectiveness of this course was evaluated by
      anonymous genomics knowledge surveys, course evaluations and unsolicited student
      comments. RESULTS: Data demonstrate this course engendered a significant increase
      in genomics knowledge and a positive perspective towards PGx. CONCLUSION: A
      course such as this bridges the current PGx basic science knowledge gap and can
      serve as a template for providing fundamental genomics knowledge until admissions
      prerequisites ensure that all incoming students are ready to embrace PGx.

PMID- 24329190
TI  - Association between CYP2D6 genotypes and the clinical outcomes of adjuvant
      tamoxifen for breast cancer: a meta-analysis.
AB  - AIM: Tamoxifen is one of the most commonly used endocrine therapeutic agents for
      breast cancer. Although many studies have examined whether the treatment outcomes
      of tamoxifen for breast cancer differ according to CYP2D6 genotype, the study
      results have been inconsistent, and the role of CYP2D6 in the prediction of
      patient outcomes from tamoxifen therapy remains controversial. This study
      evaluated the association between CYP2D6 genotypes and postoperative tamoxifen
      treatment outcome in patients with breast cancer, using the available previous
      study results. MATERIALS & METHODS: We performed a meta-analysis of ten previous
      clinical reports (n = 5183) to evaluate the association between CYP2D6 genotype
      and hazard ratios for the recurrence risk of breast cancer after postoperative
      tamoxifen treatment. Pooled estimates of hazard ratios were computed using R and
      NONMEM(r) software. RESULTS: A significantly increased risk of breast cancer
      recurrence in patients carrying variant CYP2D6 genotypes was found in this
      investigation. The mean hazard ratios and 95% CI were 1.60 (1.04-2.47) in the
      random effect model implemented in R and 1.63 (1.01-2.62) in the random effect
      model in NONMEM. The bootstrap result (2000 replicates) of NONMEM was 1.64 (1.07
      2.79). CONCLUSION: Our present findings suggest that genetic polymorphisms of
      CYP2D6 may be important predictors of the clinical outcomes of adjuvant tamoxifen
      treatment for the patients with breast cancer. A large-scale, prospective,
      randomized, well-controlled trial is warranted to confirm our findings.

PMID- 24329191
TI  - Pharmacogenomics of sterol synthesis and statin use in schizophrenia subjects
      treated with antipsychotics.
AB  - OBJECTIVE: Patients with schizophrenia treated with antipsychotics often develop
      metabolic side effects including dyslipidemia. Antipsychotics potentially
      upregulate gene expression of a lipid metabolism pathway protein called SREBP via
      SREB transcription factors (SREBFs). Genetic variation within SREBF may
      contribute to dyslipidemias and lipid medication efficacy within schizophrenia.
      RESULTS: A cross-sectional study of 157 patients were genotyped for SREBF1
      (rs11868035) and SREBF2 (rs1057217) variants, and assessed for fasting lipids.
      The cohort's mean age was 46.6 years, was 64% male and 86% were using atypical
      antipsychotics. When stratified by statin use, those receiving a statin and
      carrying the SREBF1 T allele exhibited higher total cholesterol levels (p =
      0.01), triglyceride levels (p = 0.04) and low-density lipoprotein levels (p =
      0.03). A regression analysis controlling for gender differences in lipids showed
      that the SREBF1 T allele and statin interaction remained only for total
      cholesterol levels (F[4,149] = 5.8; p < 0.0001). CONCLUSION: For schizophrenia
      individuals with the SREBF1 rs11868035 T allele, incomplete response to statin
      medications may be seen. Future investigations may allow for personalizing
      dyslipidemia treatment based on pharmacogenetics within schizophrenia.

PMID- 24329193
TI  - Application of genotype-guided cancer therapy in solid tumors.
AB  - Given the interpatient biological heterogeneity and narrow therapeutic index of
      anticancer drugs, a practical method for personalizing cancer therapy is
      essential. Genotype-guided cancer therapy will provide an optimal approach to
      normalize systemic drug exposures, predict drug toxicities and/or enrich clinical
      efficacy. To date, over a dozen anticancer drugs approved by the US FDA require
      labeling regarding pharmacogenetic biomarkers (both germline and somatic). Many,
      but not all, have prospective, genotype-guided evidence-based data. Optimizing
      output from retrospective, prospective, cost-effectiveness and adaptive biomarker
      driven clinical trials will help drive the success of personalized cancer
      therapy. This review will discuss prospective genotype-guided clinical trials in
      patients with solid tumors and address barriers in clinical translation. 

PMID- 24329194
TI  - Individualizing clozapine and risperidone treatment for schizophrenia patients.
AB  - Schizophrenia is a severe disorder that significantly affects the quality of life
      and total functioning of patients and their caregivers. Clozapine is the first
      atypical antipsychotic with fewer adverse effects and established efficacy. As a
      rule of thumb, risperidone is one of the most reliable and effective
      antipsychotics for newly diagnosed and chronic schizophrenics. Pharmacogenetic
      studies have identified genomic variants of candidate genes that seem to be
      important in the way a patient responds to treatment. The recent progress made in
      pharmacogenomics will improve the quality of treatment, since drug doses will be
      tailored to the special needs of each patient. In this article, we review the
      available literature attempting to delineate the role of genomic variations in
      clozapine and risperidone response in schizophrenic patients of various
      ethnicities. We conclude that pharmacogenomics for these two drugs is still not
      ready for implementation in the clinic. 

PMID- 24329192
TI  - Pharmacogenetics and individualizing drug treatment during pregnancy.
AB  - Pharmacogenetics as a tool to aid clinicians implement individualized
      pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in
      pregnancy is still a developing field. However, there are several areas of
      obstetric therapeutics where data are emerging that give glimpses into future
      therapeutic possibilities. These include opioid pain management, antihypertensive
      therapy, antidepressant medications, preterm labor tocolytics, antenatal
      corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few.
      More data are needed to populate the therapeutic models and to truly determine if
      pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The
      objective of this review is to summarize current data and highlight research
      needs. 

PMID- 24329195
TI  - Pharmacogenetics of taste: turning bitter pills sweet?
AB  - Poor palatability of oral drug formulations used for young children negatively
      influences medication intake, resulting in suboptimal treatment. Some children
      are more sensitive to bitter tastes than others. Bitter tasting status is
      currently assessed by phenotyping with 6-n-propylthiouracil (PROP) as a bitter
      probe. Recent studies showed that interindividual differences in PROP sensitivity
      can be largely explained by three SNPs in TAS2R38, encoding a bitter taste
      receptor. Gustin, involved in the development of taste buds, and the sweet
      receptor genotype potentially explain remaining parts of PROP sensitivity
      variability. Other TAS2 receptor bitter receptor genes may also play a role in
      bitter aversions. Dependent on their genotype, children may have different
      medication formulation preferences. Taste genetics could improve drug acceptance
      by enabling better-informed choices on adapting oral formulations to children's
      taste preferences. This paper presents an overview of recent findings concerning
      bitter taste genetics and discusses these in the context of pediatric drug
      formulation. 

PMID- 24329197
TI  - Shear thickening in granular suspensions: interparticle friction and dynamically
      correlated clusters.
AB  - We consider the shear rheology of concentrated suspensions of non-Brownian
      frictional particles. The key result of our study is the emergence of a
      pronounced shear-thickening regime, where frictionless particles would normally
      undergo shear thinning. We can clarify that shear thickening in our simulations
      is due to enhanced energy dissipation via frictional interparticle forces.
      Moreover, we evidence the formation of dynamically correlated particle clusters
      of size xi, which contribute to shear thickening via an increase in viscous
      dissipation. A scaling argument gives for the associated viscosity eta(v)~xi(2),
      which is in very good agreement with the data.

PMID- 24329196
TI  - Antihyperalgesic effects of imidazoline I(2) receptor ligands in rat models of
      inflammatory and neuropathic pain.
AB  - BACKGROUND AND PURPOSE: A new imidazoline I2 receptor ligand, CR4056, is
      effective for chronic inflammatory pain and diabetic neuropathy. However, it is
      unclear whether other I2 receptor ligands have similar effects and whether
      antinociceptive tolerance develops with repeated treatment. EXPERIMENTAL
      APPROACH: The Von Frey filament test was used to measure mechanical hyperalgesia
      and the plantar test to measure thermal hyperalgesia in rats injected with
      complete Freund's adjuvant (CFA) treatment or had undergone surgery to induce
      chronic constriction injury (CCI), models of inflammatory pain and peripheral
      neuropathic pain respectively. The effects of morphine and I2 receptor ligands, 2
      BFI, BU224, tracizoline and CR4056, 3.2-32 mg.kg(-1) , i.p., on hyperalgesia or
      affective pain (as measured by a place escape/avoidance paradigm) were studied in
      separate experiments. KEY RESULTS: Morphine and the I2 receptor ligands (2-BFI,
      BU224 and tracizoline) all dose-dependently attenuated mechanical and thermal
      hyperalgesia in CFA-treated rats. The anti-hyperalgesic effects of 2-BFI in CFA
      treated and CCI rats were attenuated by the I2 receptor antagonist idazoxan. The
      combination of 2-BFI and morphine produced additive effects against mechanical
      hyperalgesia in CFA-treated rats. Repeated treatment (daily for 7-9 days) with 2
      BFI or CR4056 did not produce antinociceptive tolerance in CFA-treated or CCI
      rats. Morphine and the I2 receptor ligands (2-BFI, BU224 and CR4056) were all
      effective at attenuating place escape/avoidance behaviour in CFA-treated rats.
      CONCLUSIONS AND IMPLICATIONS: Imidazoline I2 receptor ligands have
      antihyperalgesic effects in rat models of inflammatory and neuropathic pain and
      may represent a new class of pharmacotherapeutics for the management of chronic
      pain.

PMID- 24329198
TI  - Brownian motion and the hydrodynamic friction tensor for colloidal particles of
      complex shape.
AB  - We synthesize colloidal particles with various anisotropic shapes and track their
      orientationally resolved Brownian trajectories using confocal microscopy. An
      analysis of appropriate short-time correlation functions provides direct access
      to the hydrodynamic friction tensor of the particles revealing nontrivial
      couplings between the translational and rotational degrees of freedom. The
      results are consistent with calculations of the hydrodynamic friction tensor in
      the low-Reynolds-number regime for the experimentally determined particle shapes.

PMID- 24329199
TI  - Hidden solidlike properties in the isotropic phase of the 8CB liquid crystal.
AB  - Novel dynamic experiments have enabled the identification of a macroscopic
      solidlike response in the isotropic phase of a low molecular weight liquid
      crystal, 4,4'-n-octylcyanobiphenyl (8CB). This unknown property indicates that
      the low frequency shear elasticity identified in the isotropic phase of liquid
      crystal polymers is not reminiscent from the glass transition but reveals likely
      a generic property of the liquid state. The comparison to high molecular weight
      liquid crystals indicates, however, that the shear modulus is much enhanced when
      the liquid crystal moieties are attached to a polymer chain. The macroscopic
      length scales probed (0.050-0.100 mm) exclude wall-induced effects. 

PMID- 24329200
TI  - Dynamics of defects in an active nematic layer.
AB  - Defect dynamics in a thin active nematic layer is studied by asymptotic matching
      of solutions in the defect core and the far field. The analysis is facilitated by
      the correspondence between the two-dimensional nematic and complex scalar field
      models. Self-propulsion and topological interactions are identified as the
      primary drivers of the defect motion, surpassing the influence of both passive
      backflow and active flow induced by other defects. 

PMID- 24329201
TI  - Apparent flexoelectricity in lipid bilayer membranes due to external charge and
      dipolar distributions.
AB  - In this Rapid Communication we show that the interplay between the deformation
      geometric-nonlinearity and distributions of external charges and dipoles lead to
      the renormalization of the membrane's native flexoelectric response. Our work
      provides a framework for a mesoscopic interpretation of flexoelectricity and if
      necessary, artificially "design" tailored flexoelectricity in membranes.
      Comparisons with experiments indicate reasonable quantitative agreement. 

PMID- 24329202
TI  - Contact-based social contagion in multiplex networks.
AB  - We develop a theoretical framework for the study of epidemiclike social contagion
      in large scale social systems. We consider the most general setting in which
      different communication platforms or categories form multiplex networks.
      Specifically, we propose a contact-based information spreading model, and show
      that the critical point of the multiplex system associated with the active phase
      is determined by the layer whose contact probability matrix has the largest
      eigenvalue. The framework is applied to a number of different situations,
      including a real multiplex system. Finally, we also show that when the system
      through which information is disseminating is inherently multiplex, working with
      the graph that results from the aggregation of the different layers is
      inaccurate. 

PMID- 24329203
TI  - Highly dispersed networks by enhanced redirection.
AB  - We introduce a class of networks that grow by enhanced redirection. Nodes are
      introduced sequentially, and each either attaches to a randomly chosen target
      node with probability 1-r or to the parent of the target with probability r,
      where r is an increasing function of the degree of the parent. This mechanism
      leads to highly dispersed networks with unusual properties: (i) existence of
      multiple macrohubs-nodes whose degree is a finite fraction of the total number of
      network nodes N, (ii) lack of self-averaging, and (iii) anomalous scaling, in
      which N(k), the number of nodes of degree k scales as N(k)~N(nu-1)/k(nu), with
      1<nu<2.

PMID- 24329204
TI  - Triple point in correlated interdependent networks.
AB  - Many real-world networks depend on other networks, often in nontrivial ways, to
      maintain their functionality. These interdependent "networks of networks" are
      often extremely fragile. When a fraction 1-p of nodes in one network randomly
      fails, the damage propagates to nodes in networks that are interdependent and a
      dynamic failure cascade occurs that affects the entire system. We present dynamic
      equations for two interdependent networks that allow us to reproduce the failure
      cascade for an arbitrary pattern of interdependency. We study the "rich club"
      effect found in many real interdependent network systems in which the high-degree
      nodes are extremely interdependent, correlating a fraction alpha of the higher
      degree nodes on each network. We find a rich phase diagram in the plane p-alpha,
      with a triple point reminiscent of the triple point of liquids that separates a
      nonfunctional phase from two functional phases. 

PMID- 24329205
TI  - Generalizing the transition from amplitude to oscillation death in coupled
      oscillators.
AB  - Amplitude death (AD) and oscillation death (OD) are two structurally different
      oscillation quenching types in coupled nonlinear oscillators. The transition from
      AD to OD has been recently realized due to the interplay between heterogeneity
      and coupling strength [A. Koseska et al., Phys. Rev. Lett. 111, 024103 (2013)].
      We identify here the transition from AD to OD in nonlinear oscillators with
      couplings of distinct natures. It is demonstrated that the presence of time delay
      in the coupling cannot induce such a transition in identical oscillators, but it
      can indeed facilitate its occurrence with a low degree of heterogeneity.
      Moreover, it is further shown that the AD to OD transition is reliably observed
      in identical oscillators with dynamic and conjugate couplings. The coexistence of
      AD and OD and rich stable OD configurations after the transition are revealed,
      which are of great significance for potential applications in physics, biology,
      and control studies. 

PMID- 24329206
TI  - Initial microfluidic dissolution regime of CO2 bubbles in viscous oils.
AB  - We examine the initial dynamical behavior of dissolving microbubbles composed of
      carbon dioxide gas in highly viscous silicone oils over a range of flow rates and
      pressure conditions. Microfluidic periodic trains of CO(2) bubbles are used to
      probe the interrelation between bubble dissolution and high-viscosity multiphase
      flows in microgeometries. We investigate bubble morphology from low to large
      capillary numbers and calculate the effective mass diffusion flux across the
      interface by tracking and monitoring individual bubbles during shrinkage. The
      initial flux is characterized using a dissolution coefficient that reveals the
      influence of the oil molecular weight on the dissolution process. Our findings
      show the possibility to control and exploit the interplay between capillary and
      mass transfer phenomena with highly viscous fluids in small-scale systems.

PMID- 24329207
TI  - Experimental realization of a water-wave metamaterial shifter.
AB  - We demonstrate by quantitative experimental measurements that metamaterials with
      anisotropic properties can be used in the context of water waves to produce a
      reflectionless bent waveguide. The anisotropic medium consists in a bathymetry
      with subwavelength layered structure that shifts the wave in the direction of the
      waveguide bending (10 degrees , 20 degrees , and 30 degrees ). The waveguide
      filled with such metamaterial is tested experimentally and compared to a
      reference empty bent waveguide. The experimental method used to characterize the
      wave field allows for space-time resolved measurements of water elevation.
      Results show the efficiency of the shifter. Modal treatment of the experimental
      data confirms that the metamaterial prevents higher modes from being excited in
      the waveguide.

PMID- 24329208
TI  - Multistage structural evolution in simple monatomic supercritical fluids:
      superstable tetrahedral local order.
AB  - The local order units of dense simple liquid are typically three-dimensional
      (close packed) clusters: hcp, fcc, and icosahedrons. We show that the fluid
      demonstrates the superstable tetrahedral local order up to temperatures several
      orders of magnitude higher than the melting temperature and down to critical
      density. While the solid-like local order (hcp, fcc) disappears in the fluid at
      much lower temperatures and far above critical density. We conclude that the
      supercritical fluid shows the temperature (density)-driven two-stage "melting" of
      the three-dimensional local order. We also find that the structure relaxation
      times in the supercritical fluid are much larger than ones estimated for weakly
      interactive gas even far above the melting line. 

PMID- 24329209
TI  - Percolation with long-range correlated disorder.
AB  - Long-range power-law correlated percolation is investigated using Monte Carlo
      simulations. We obtain several static and dynamic critical exponents as functions
      of the Hurst exponent H, which characterizes the degree of spatial correlation
      among the occupation of sites. In particular, we study the fractal dimension of
      the largest cluster and the scaling behavior of the second moment of the cluster
      size distribution, as well as the complete and accessible perimeters of the
      largest cluster. Concerning the inner structure and transport properties of the
      largest cluster, we analyze its shortest path, backbone, red sites, and
      conductivity. Finally, bridge site growth is also considered. We propose
      expressions for the functional dependence of the critical exponents on H. 

PMID- 24329210
TI  - Weak-noise limit of a piecewise-smooth stochastic differential equation.
AB  - We investigate the validity and accuracy of weak-noise (saddle-point or
      instanton) approximations for piecewise-smooth stochastic differential equations
      (SDEs), taking as an illustrative example a piecewise-constant SDE, which serves
      as a simple model of Brownian motion with solid friction. For this model, we show
      that the weak-noise approximation of the path integral correctly reproduces the
      known propagator of the SDE at lowest order in the noise power, as well as the
      main features of the exact propagator with higher-order corrections, provided the
      singularity of the path integral associated with the nonsmooth SDE is treated
      with some heuristics. We also show that, as in the case of smooth SDEs, the
      deterministic paths of the noiseless system correctly describe the behavior of
      the nonsmooth SDE in the low-noise limit. Finally, we consider a smooth
      regularization of the piecewise-constant SDE and study to what extent this
      regularization can rectify some of the problems encountered when dealing with
      discontinuous drifts and singularities in SDEs. 

PMID- 24329211
TI  - Topography of chance.
AB  - We present a model of multiplicative Langevin dynamics that is based on two
      foundations: the Langevin equation and the notion of multiplicative evolution.
      The model is a nonlinear mechanism transforming a white-noise input to a dynamic
      equilibrium output, using a single control: an underlying convex U-shaped
      potential function. The output is quantified by a stationary density which can
      attain a given number of shapes and a given number of randomness categories. The
      model generates each admissible combination of the output's shape and randomness
      in a universal and robust fashion. Moreover, practically all the probability
      distributions that are supported on the positive half-line, and that are commonly
      encountered and applied across the sciences, can be reverse engineered by this
      model. Hence, this model is a universal equilibrium mechanism, in the context of
      multiplicative dynamics, for the robust generation of "chance": the model's
      output. In turn, the properties of the produced "chance," the output's shape and
      randomness, are determined with mathematical precision by the control's
      landscape, its topography. Thus, a topographic map of chance is established. As a
      particular application, probability distributions with power-law tails are shown
      to be universally and robustly generated by controls on the "edge of convexity":
      convex U-shaped potential functions with asymptotically linear wings. 

PMID- 24329212
TI  - Pulling alternating copolymers adsorbed on a striped surface.
AB  - We consider a partially directed walk model of a strictly alternating copolymer
      adsorbing on a striped surface where the energy is associated with the numbers of
      the two types of monomers adsorbed on the two types of surface sites. A force is
      applied to the last monomer and the polymer responds to this force, sometimes by
      desorbing. The force can be applied at various angles, with the surface component
      parallel or perpendicular (or at some other angle) to the stripe direction. The
      desorption behavior is strongly dependent on the force direction and the response
      gives information about the shape and direction of the polymer adsorbed on the
      surface, especially at low temperatures. In some cases the ground state is
      degenerate and this also has an important effect on the temperature dependence of
      the critical force needed for desorption. We give a complete solution of the
      problem using generating function techniques and an approximate treatment that is
      especially useful at low temperatures and helps in our physical understanding of
      the situation. 

PMID- 24329213
TI  - Green function of the double-fractional Fokker-Planck equation: path integral and
      stochastic differential equations.
AB  - The statistics of rare events, the so-called black-swan events, is governed by
      non-Gaussian distributions with heavy power-like tails. We calculate the Green
      functions of the associated Fokker-Planck equations and solve the related
      stochastic differential equations. We also discuss the subject in the framework
      of path integration. 

PMID- 24329214
TI  - Probability distributions extremizing the nonadditive entropy S(delta) and
      stationary states of the corresponding nonlinear Fokker-Planck equation.
AB  - Under the assumption that the physically appropriate entropy of generic complex
      systems satisfies thermodynamic extensivity, we investigate the recently
      introduced entropy S(delta) (which recovers the usual Boltzmann-Gibbs form for
      delta=1) and establish the microcanonical and canonical extremizing
      distributions. Using a generalized version of the H theorem, we find the
      nonlinear Fokker-Planck equation associated with that entropic functional and
      calculate the stationary-state probability distributions. We demonstrate that
      both approaches yield one and the same equation, which in turn uniquely
      determines the probability distribution. We show that the equilibrium
      distributions asymptotically behave like stretched exponentials, and that, in
      appropriate probability-energy variables, an interesting return occurs at
      delta=4/3. As a mathematically simple illustration, we consider the one
      dimensional harmonic oscillator and calculate the generalized chemical potential
      for different values of delta.

PMID- 24329215
TI  - Resonant enhancement of Anderson localization: analytical approach.
AB  - We study localization properties of the eigenstates and wave transport in a one
      dimensional system consisting of a set of barriers and/or wells of fixed
      thickness and random heights. The inherent peculiarity of the system resulting in
      the enhanced Anderson localization is the presence of the resonances emerging due
      to the coherent interaction of the waves reflected from the interfaces between
      the wells and/or barriers. Our theoretical approach allows to derive the
      localization length in infinite samples both out of the resonances and close to
      them. We examine how the transport properties of finite samples can be described
      in terms of this length. It is shown that the analytical expressions obtained by
      standard methods for continuous random potentials can be used in our discrete
      model, in spite of the presence of resonances that cannot be described by
      conventional theories. All our results are illustrated with numerical data
      manifesting an excellent agreement with the theory. 

PMID- 24329216
TI  - Frenetic origin of negative differential response.
AB  - The Green-Kubo formula for linear response coefficients is modified when dealing
      with nonequilibrium dynamics. In particular, negative differential conductivities
      are allowed to exist away from equilibrium. We give a unifying framework for such
      a negative differential response in terms of the frenetic contribution in the
      nonequilibrium formula. It corresponds to a negative dependence of the escape
      rates and reactivities on the driving forces. Partial caging in state space and
      reduction of dynamical activity with increased driving cause the current to drop.
      These are time-symmetric kinetic effects that are believed to play a major role
      in the study of nonequilibria. We give various simple examples treating particle
      and energy transport, which all follow the same pattern in the dependence of the
      dynamical activity on the nonequilibrium driving, made visible from recently
      derived nonequilibrium response theory. 

PMID- 24329217
TI  - Critical Casimir forces between homogeneous and chemically striped surfaces.
AB  - Recent experiments have measured the critical Casimir force acting on a colloid
      immersed in a binary liquid mixture near its continuous demixing phase transition
      and exposed to a chemically structured substrate. Motivated by these experiments,
      we study the critical behavior of a system, which belongs to the Ising
      universality class, for the film geometry with one planar wall chemically
      striped, such that there is a laterally alternating adsorption preference for the
      two species of the binary liquid mixture, which is implemented by surface fields.
      For the opposite wall we employ alternatively a homogeneous adsorption preference
      or homogeneous Dirichlet boundary conditions, which within a lattice model are
      realized by open boundary conditions. By means of mean-field theory, Monte Carlo
      simulations, and finite-size scaling analysis we determine the critical Casimir
      force acting on the two parallel walls and its corresponding universal scaling
      function. We show that in the limit of stripe widths small compared with the film
      thickness, on the striped surface the system effectively realizes Dirichlet
      boundary conditions, which generically do not hold for actual fluids. Moreover,
      the critical Casimir force is found to be attractive or repulsive, depending on
      the width of the stripes of the chemically patterned surface and on the boundary
      condition applied to the opposing surface. 

PMID- 24329218
TI  - Approximate solution to the stochastic Kuramoto model.
AB  - We study Kuramoto phase oscillators with temporal fluctuations in the
      frequencies. The infinite-dimensional system can be reduced in a Gaussian
      approximation to two first-order differential equations. This yields a solution
      for the time-dependent order parameter, which characterizes the synchronization
      between the oscillators. The known critical coupling strength is exactly
      recovered by the Gaussian theory. Extensive numerical experiments further show
      that the analytical results are very accurate below and sufficiently above the
      critical value. We obtain the asymptotic order parameter in closed form, which
      suggests a tighter upper bound for the corresponding scaling. As a last point, we
      elaborate the Gaussian approximation in complex networks with distributed
      degrees. 

PMID- 24329219
TI  - Validity of Fourier's law in one-dimensional momentum-conserving lattices with
      asymmetric interparticle interactions.
AB  - We have numerically studied heat conduction in a few one-dimensional momentum
      conserving lattices with asymmetric interparticle interactions by the
      nonequilibrium heat bath method, the equilibrium Green-Kubo method, and the heat
      current power spectra analysis. Very strong finite-size effects are clearly
      observed. Such effects make the heat conduction obey a Fourier-like law in a wide
      range of lattice lengths. However, in yet longer lattice lengths, the heat
      conductivity regains its power-law divergence. Therefore, the power-law
      divergence of the heat conductivity in the thermodynamic limit is verified, as is
      expected by many existing theories. 

PMID- 24329220
TI  - Completeness of solutions of Bethe's equations.
AB  - We consider the Bethe equations for the isotropic spin-1/2 Heisenberg quantum
      spin chain with periodic boundary conditions. We formulate a conjecture for the
      number of solutions with pairwise distinct roots of these equations, in terms of
      numbers of so-called singular (or exceptional) solutions. Using homotopy
      continuation methods, we find all such solutions of the Bethe equations for
      chains of length up to 14. The numbers of these solutions are in perfect
      agreement with the conjecture. We also discuss an indirect method of finding
      solutions of the Bethe equations by solving the Baxter T-Q equation. We briefly
      comment on implications for thermodynamical computations based on the string
      hypothesis. 

PMID- 24329221
TI  - Quantum versus classical foundation of statistical mechanics under experimentally
      realistic conditions.
AB  - Focusing on isolated macroscopic systems, described in terms of either a quantum
      mechanical or a classical model, our two key questions are how far does an
      initial ensemble (usually far from equilibrium and largely unknown in detail)
      evolve towards a stationary long-time behavior (equilibration) and how far is
      this steady state in agreement with the microcanonical ensemble as predicted by
      statistical mechanics (thermalization). A recently developed quantum mechanical
      treatment of the problem is briefly summarized, putting particular emphasis on
      the realistic modeling of experimental measurements and nonequilibrium initial
      conditions. Within this framework, equilibration can be proven under very weak
      assumptions about those measurements and initial conditions, while thermalization
      still requires quite strong additional hypotheses. An analogous approach within
      the framework of classical mechanics is developed and compared with the quantum
      case. In particular, the assumptions to guarantee classical equilibration are now
      rather strong, while thermalization then follows under relatively weak additional
      conditions. 

PMID- 24329222
TI  - Quasirelativistic Langevin equation.
AB  - We address the problem of a microscopic derivation of the Langevin equation for a
      weakly relativistic Brownian particle. A noncovariant Hamiltonian model is
      adopted, in which the free motion of particles is described relativistically
      while their interaction is treated classically, i.e., by means of action-to-a
      distance interaction potentials. Relativistic corrections to the classical
      Langevin equation emerge as nonlinear dissipation terms and originate from the
      nonlinear dependence of the relativistic velocity on momentum. On the other hand,
      similar nonlinear dissipation forces also appear as classical (nonrelativistic)
      corrections to the weak-coupling approximation. It is shown that these classical
      corrections, which are usually ignored in phenomenological models, may be of the
      same order of magnitude, if not larger than, relativistic ones. The interplay of
      relativistic corrections and classical beyond-the-weak-coupling contributions
      determines the sign of the leading nonlinear dissipation term in the Langevin
      equation and thus is qualitatively important. 

PMID- 24329223
TI  - Kinetics of the dispersion transition and nonergodicity of a system consisting of
      a disordered porous medium and a nonwetting liquid.
AB  - An approach has been proposed for the description of the dispersion transition of
      a nonwetting liquid in confinement. This approach describes intrusion and
      extrusion processes for the ground state of a disordered porous medium, which is
      characterized by the formation of a fractal percolation cluster. The observed
      transition of the system of liquid nanoclusters in confinement to a metastable
      state in a narrow range of degrees of filling and temperatures has been explained
      by the appearance of a potential barrier owing to fluctuations of the collective
      "multiparticle interaction" of liquid nanoclusters in neighboring pores of
      different sizes on the shell of the fractal percolation cluster of filled pores.
      The energy of the metastable state forms a potential relief in the space of the
      porous medium with many maxima and minima. The volume of the dispersed liquid in
      the metastable state has been calculated within the analytical percolation theory
      for the ground state with the infinite percolation cluster. The extrusion-time
      distribution function of pores has been calculated. It has been found that the
      volume of the nonwetting liquid remaining in the porous medium decreases with
      time according to a power law. Relaxation in the system under study is a
      multistep process involving discontinuous equilibrium and overcoming of many
      local maxima of the potential relief. The formation of the metastable state of
      the trapped nonwetting liquid has been attributed to the nonergodicity of the
      disordered porous medium. The model reproduces the observed dependence of the
      volume of the dispersed liquid both on the degree of filling and on the
      temperature. 

PMID- 24329224
TI  - Phase transition in random planar diagrams and RNA-type matching.
AB  - We study the planar matching problem, defined by a symmetric random matrix with
      independent identically distributed entries, taking values zero and one. We show
      that the existence of a perfect planar matching structure is possible only above
      a certain critical density, p(c), of allowed contacts (i.e., of ones). Using a
      formulation of the problem in terms of Dyck paths and a matrix model of planar
      contact structures, we provide an analytical estimation for the value of the
      transition point, p(c), in the thermodynamic limit. This estimation is close to
      the critical value, p(c)~0.379, obtained in numerical simulations based on an
      exact dynamical programming algorithm. We characterize the corresponding critical
      behavior of the model and discuss the relation of the perfect-imperfect matching
      transition to the known molten-glass transition in the context of random RNA
      secondary structure formation. In particular, we provide strong evidence
      supporting the conjecture that the molten-glass transition at T=0 occurs at p(c).

PMID- 24329225
TI  - Products of rectangular random matrices: singular values and progressive
      scattering.
AB  - We discuss the product of M rectangular random matrices with independent Gaussian
      entries, which have several applications, including wireless telecommunication
      and econophysics. For complex matrices an explicit expression for the joint
      probability density function is obtained using the Harish-Chandra-Itzykson-Zuber
      integration formula. Explicit expressions for all correlation functions and
      moments for finite matrix sizes are obtained using a two-matrix model and the
      method of biorthogonal polynomials. This generalizes the classical result for the
      so-called Wishart-Laguerre Gaussian unitary ensemble (or chiral unitary ensemble)
      at M=1, and previous results for the product of square matrices. The correlation
      functions are given by a determinantal point process, where the kernel can be
      expressed in terms of Meijer G-functions. We compare the results with numerical
      simulations and known results for the macroscopic level density in the limit of
      large matrices. The location of the end points of support for the latter are
      analyzed in detail for general M. Finally, we consider the so-called ergodic
      mutual information, which gives an upper bound for the spectral efficiency of a
      MIMO communication channel with multifold scattering. 

PMID- 24329226
TI  - Phase transitions in number theory: from the birthday problem to Sidon sets.
AB  - In this work, we show how number theoretical problems can be fruitfully
      approached with the tools of statistical physics. We focus on g-Sidon sets, which
      describe sequences of integers whose pairwise sums are different, and propose a
      random decision problem which addresses the probability of a random set of k
      integers to be g-Sidon. First, we provide numerical evidence showing that there
      is a crossover between satisfiable and unsatisfiable phases which converts to an
      abrupt phase transition in a properly defined thermodynamic limit. Initially
      assuming independence, we then develop a mean-field theory for the g-Sidon
      decision problem. We further improve the mean-field theory, which is only
      qualitatively correct, by incorporating deviations from independence, yielding
      results in good quantitative agreement with the numerics for both finite systems
      and in the thermodynamic limit. Connections between the generalized birthday
      problem in probability theory, the number theory of Sidon sets and the properties
      of q-Potts models in condensed matter physics are briefly discussed. 

PMID- 24329227
TI  - Postcritical behavior of a gelling system.
AB  - The formation of a gel in a disperse coagulating system, wherein binary
      coagulation governs the temporal changes of the particle mass spectrum is studied
      for the coagulation kernel proportional to K(g,l)=gl with g,l being the numbers
      of monomers in the coalescing pair of particles. This model is known to reveal
      the sol-gel transition, i.e., the formation of one giant cluster with the mass
      comparable to the total mass of the whole system. This paper reports on some
      exact results that are valid for arbitrary initial particle mass spectra. The
      particle spectrum is shown to be expressed through a contour integral of the
      exponentiated initial generating function of the particle mass spectrum. The
      exact formula for the gel mass is derived for the scenario of passive gelation.
      Two scenarios of gelation, where the gel is either active or passive, are
      considered. 

PMID- 24329228
TI  - Integral quantum fluctuation theorems under measurement and feedback control.
AB  - We derive integral quantum fluctuation theorems and quantum Jarzynski equalities
      for a feedback-controlled system and a memory which registers outcomes of the
      measurement. The obtained equalities involve the information content, which
      reflects the information exchange between the system and the memory, and take
      into account the back action of a general measurement contrary to the classical
      case. The generalized second law of thermodynamics under measurement and feedback
      control is reproduced from these equalities. 

PMID- 24329229
TI  - Three-site interacting spin chain in a staggered field: fidelity versus Loschmidt
      echo.
AB  - We study the the ground state fidelity and the ground state Loschmidt echo of a
      three-site interacting XX chain in presence of a staggered field which exhibits
      special types of quantum phase transitions due to change in the topology of the
      Fermi surface, apart from quantum phase transitions from gapped to gapless
      phases. We find that, on one hand, the fidelity is able to detect only the
      boundaries separating the gapped from the gapless phase; it is completely
      insensitive to the phase transition from the two Fermi points region to the four
      Fermi points region lying within this gapless phase. On the other hand, the
      Loschmidt echo shows a dip only at a special point in the entire phase diagram
      and hence fails to detect any quantum phase transition associated with the
      present model. We provide appropriate arguments in support of this anomalous
      behavior. 

PMID- 24329230
TI  - dc electric field effect on the anomalous exponent of the hopping conduction in
      the one-dimensional disorder model.
AB  - The dc electric field effect on the anomalous exponent of the hopping conduction
      in the disorder model is investigated. First, we explain the model and derive an
      analytical expression of the effective waiting time for the general case. We show
      that the exponent depends on the external field. Then we focus on a one
      dimensional system in order to illustrate the features of the anomalous exponent.
      We derive approximate expressions of the anomalous exponent of the system
      analytically. For the case of a weak field, the anomalous exponent is consistent
      with that of diffusive systems. This is consistent with the treatments of Barkai
      et al. [Phys. Rev. E 63, 046118 (2001)] and our result supports their theory. On
      the other hand, for the case of a strong field and a strong disorder, the time
      evolution of the exponent clearly differs from that in the weak field. The
      exponent is consistent with the well-known expression of the anomalous exponent
      in the multiple trapping model at mesoscopic time scales. In the long-time limit,
      a transition of the anomalous exponent to the same value of the weak field
      occurs. These findings are verified by the Monte Carlo simulation. 

PMID- 24329231
TI  - Time asymmetry of the Kramers equation with nonlinear friction: fluctuation
      dissipation relation and ratchet effect.
AB  - We show by numerical simulations that the presence of nonlinear velocity
      dependent friction forces can induce a finite net drift in the stochastic motion
      of a particle in contact with an equilibrium thermal bath and in an asymmetric
      periodic spatial potential. In particular, we study the Kramers equation for a
      particle subjected to Coulomb friction, namely a constant force acting in the
      direction opposite to the particle's velocity. We characterize the nonequilibrium
      irreversible dynamics by studying the generalized fluctuation-dissipation
      relation for this ratchet model driven by Coulomb friction. 

PMID- 24329232
TI  - Ising-like phase transition of an n-component Eulerian face-cubic model.
AB  - By means of Monte Carlo simulations and a finite-size scaling analysis, we find a
      critical line of an n-component Eulerian face-cubic model on the square lattice
      and the simple cubic lattice in the region v>1, where v is the bond weight. The
      phase transition belongs to the Ising universality class independent of n. The
      critical properties of the phase transition can also be captured by the
      percolation of the complement of the Eulerian graph. 

PMID- 24329233
TI  - Occupation times on a comb with ramified teeth.
AB  - We investigate occupation time statistics for random walks on a comb with
      ramified teeth. This is achieved through the relation between the occupation time
      and the first passage times. Statistics of occupation times in half space follows
      Lamperti's distribution, i.e., the generalized arcsine law holds. Transitions
      between different behaviors are observed, which are controlled by the size of the
      backbone and teeth of the comb, as well as bias. Occupation time on a nonsimply
      connected domain is analyzed with a mean-field theory and numerical simulations.
      In that case, the generalized arcsine law is not valid. 

PMID- 24329234
TI  - Reduced density matrix for nonequilibrium steady states: a modified Redfield
      solution approach.
AB  - We describe a method to obtain the reduced density matrix (RDM) correct up to
      second order in system-bath coupling in nonequilibrium steady-state situations.
      The RDM is obtained via a scheme based on analytic continuation, using the time
      local Redfield-like quantum master equation, which was earlier used by the same
      authors [J. Chem. Phys. 136, 194110 (2012)] to obtain the correct thermal
      equilibrium description. This nonequilibrium modified Redfield solution is then
      corroborated with the exact RDM obtained via the nonequilibrium Green's function
      technique for the quantum harmonic oscillator. Lastly, the scheme is compared to
      different quantum master equations (QMEs), namely the time-local Redfield-like
      and the Lindblad-like QMEs, in order to illustrate the differences between each
      of these approaches. 

PMID- 24329235
TI  - Heat transport enhanced by optical phonons in one-dimensional anharmonic lattices
      with alternating bonds.
AB  - In lattice systems, the effects of optical phonons on heat transport are usually
      neglected due to their relatively small group velocities compared with acoustic
      phonons, or even assumed to be negative because introducing optical phonons may
      simultaneously reduce the group velocities of acoustic phonons. In order to well
      understand the role played by optical phonons, we propose a one-dimensional
      anharmonic lattice model with alternating interactions, where the optical phonons
      can be conveniently tuned. We find that in contrast to previous studies, the
      optical phonons (in coordination with the nonlinearities) can enhance heat
      transport in the thermodynamical limit, suggesting that optical phonons can also
      play an active role. The underlying mechanism is related to the effects of two
      kinds of nonlinear excitations, i.e., the optical and the gap discrete breathers
      (DBs). These DBs release energy and in turn facilitate heat transport. 

PMID- 24329236
TI  - Critical Casimir forces along the isofields.
AB  - Using quasiexact numerical density-matrix renormalization-group techniques we
      calculate the critical Casimir force for a two-dimensional (2D) Ising strip with
      equal strong surface fields, along the thermodynamic paths corresponding to the
      fixed nonzero bulk field h?0. Using the Derjaguin approximation we also determine
      the critical Casimir force and its potential for two disks. We find that varying
      the temperature along the isofields lying between the bulk coexistence and the
      capillary condensation critical point leads to a dramatic increase of the
      critical Casimir interactions with a qualitatively different functional
      dependence on the temperature than along h=0. These findings might be of
      relevance for biomembranes, whose heterogeneity is recently interpreted as being
      connected with a critical behavior belonging to the 2D Ising universality class. 

PMID- 24329237
TI  - Contact processes in crowded environments.
AB  - Periodically sheared colloids at low densities demonstrate a dynamical phase
      transition from an inactive to active phase as the strain amplitude is increased.
      The inactive phase consists of no collisions (contacts) between particles in the
      steady state limit, while in the active phase collisions persist. To investigate
      this system at higher densities, we construct and study a conserved-particle
      number contact process with three-body interactions, which are potentially more
      likely than two-body interactions at higher densities. For example, consider one
      active (diffusing) particle colliding with two inactive (nondiffusing) particles
      such that they become active and consider spontaneous inactivation. In mean
      field, this system exhibits a continuous dynamical phase transition. Simulations
      on square lattices also indicate a continuous transition with exponents similar
      to those measured for the conserved lattice gas (CLG) model. In contrast, the
      three-body interaction requiring two active particles to activate one inactive
      particle exhibits a discontinuous transition. Finally, inspired by kinetically
      constrained models of the glass transition, we investigate the "caging effect" at
      even higher particle densities to look for a second dynamical phase transition
      back to an inactive phase. Square lattice simulations suggest a continuous
      transition with a new set of exponents differing from both the CLG model and what
      is known as directed percolation, indicating a potentially new universality class
      for a contact process with a conserved particle number. 

PMID- 24329238
TI  - Optimization of the monolayer growth in adsorption-desorption processes.
AB  - Kinetics of the deposition process of dimers in the presence of desorption is
      studied by Monte Carlo method on a one-dimensional lattice. The aim of this work
      is to investigate how do various temporal dependencies of the desorption rate
      hasten or slow down the deposition process. The growth of the coverage theta(t)
      above the jamming limit to its steady-state value theta(infinity) is analyzed
      when the desorption probability P(des) decreases both stepwise and linearly
      (continuously) over a certain time domain. We report a numerical evidence that
      the time needed for a system to reach the given coverage theta can be
      significantly reduced if P(des) decreases in time. Finally, a self-consistent
      optimization procedure, when the probability P(des) depends on the current
      coverage density theta(t), is formulated and tested. The present model reproduces
      qualitatively the densification kinetics and the memory effects of vibrated
      granular materials. Our results suggest that the process of vibratory compaction
      of granular materials can be optimized by using a time dependent intensity of
      external excitations.

PMID- 24329239
TI  - Transition state theory and the dynamics of hard disks.
AB  - The dynamics of two- and five-disk systems confined in a square has been studied
      using molecular dynamics simulations and compared with the predictions of
      transition state theory. We determine the partition functions Z and Z(?) of
      transition state theory using a procedure first used by Salsburg and Wood for the
      pressure. Our simulations show this procedure and transition state theory are in
      excellent agreement with the simulations. A generalization of the transition
      state theory to the case of a large number of disks N is made and shown to be in
      full agreement with simulations of disks moving in a narrow channel. The same
      procedure for hard spheres in three dimensions leads to the Vogel-Fulcher-Tammann
      formula for their alpha relaxation time.

PMID- 24329240
TI  - Thermal fluctuations and stability of a particle levitated by a repulsive Casimir
      force in a liquid.
AB  - We study the vertical Brownian motion of a gold particle levitated by a repulsive
      Casimir force to a silica plate immersed in bromobenzene. The time evolution of
      the particle distribution starting from an equilibrium position, where the
      Casimir force and gravitational force are balanced, is considered by solving the
      Langevin equation using the Monte Carlo method. When the gold particle is very
      close to the silica plate, the Casimir force changes from repulsive to
      attractive, and the particle eventually sticks to the surface. The escape rate
      from a metastable position is calculated by solving the Fokker-Plank equation; it
      agrees with the value obtained by Kramers' escape theory. The duration of
      levitation increases as the particle radius increases up to around 2.3 MUm. As an
      example, we show that a 1-MUm-diameter gold particle can be levitated for a
      significantly long time by the repulsive Casimir force at room temperature. 

PMID- 24329241
TI  - Information exchange dynamics of the two-dimensional XY model.
AB  - Information exchange dynamics of the two-dimensional XY model is studied by means
      of the entropic sampling algorithm. Combining the analytic and numerical results,
      we obtain the entropy in the whole range of the energy at various system sizes.
      The time evolution of the order parameter and of the number of vortices is
      explored, and the corresponding relaxation times are found to grow algebraically
      with the system size. Such absence of characteristic time scales in the
      thermodynamic limit manifests the emergent criticality of the exchanging process
      of information with the environment. The mechanism of information exchange in the
      XY model is discussed in terms of the dynamic exponents, in comparison with the
      Ising model. 

PMID- 24329242
TI  - Thermal phase transitions in a honeycomb lattice gas with three-body
      interactions.
AB  - We study the thermal phase transitions in a classical (hard-core) lattice gas
      model with nearest-neighbor three-body interactions on the honeycomb lattice,
      based on parallel tempering Monte Carlo simulations. This system realizes
      incompressible low-temperature phases at fractional fillings of 9/16, 5/8, and
      3/4 that were identified in a previous study of a related quantum model. In
      particular, both the 9/16 and the 5/8 phase exhibit an extensive ground-state
      degeneracy reflecting the frustrated nature of the three-body interactions on the
      honeycomb lattice. The thermal melting of the 9/16 phase is found to be a first
      order, discontinuous phase transition. On the other hand, from the thermodynamic
      behavior we obtain indications for a four-states Potts-model thermal transition
      out of the 5/8 phase. We find that this thermal Potts-model transition relates to
      the selection of one out of four extensive sectors within the low-energy manifold
      of the 5/8 phase, which we obtain via an exact mapping of the ground-state
      manifold to a hard-core dimer model on an embedded honeycomb superlattice. 

PMID- 24329243
TI  - Transport in a chain of asymmetric cavities: effects of the concentration with
      hard-core interaction.
AB  - We studied the transport process of overdamped Brownian particles, in a chain of
      asymmetric cavities, interacting through a hard-core potential. When a force is
      applied in opposite directions a difference in the drift velocity of the
      particles inside the cavity can be observed. Previous works on similar systems
      deal with the low-concentration regime, in which the interaction is irrelevant.
      In this case it was found that large particles show a stronger asymmetry in the
      drift velocity when a small force is applied, allowing for the separation of
      different size particles [Reguera et al., Phys. Rev. Lett. 108, 020604 (2012)].
      We found that when the interaction between particles is considered, the behavior
      of the system is substantially different. For example, as concentration is
      increased, the small particles are the ones that show a stronger asymmetry. For
      the case where all the particles in the system are of the same size we took
      advantage of the particle-vacancy analogy to predict that the left and right
      currents are almost equal in a region around the concentration 0.5 despite the
      asymmetry of the cavity. 

PMID- 24329244
TI  - Quasistationarity in a model of long-range interacting particles moving on a
      sphere.
AB  - We consider a long-range interacting system of N particles moving on a spherical
      surface under an attractive Heisenberg-like interaction of infinite range and
      evolving under deterministic Hamilton dynamics. The system may also be viewed as
      one of globally coupled Heisenberg spins. In equilibrium, the system has a
      continuous phase transition from a low-energy magnetized phase, in which the
      particles are clustered on the spherical surface, to a high-energy homogeneous
      phase. The dynamical behavior of the model is studied analytically by analyzing
      the Vlasov equation for the evolution of the single-particle distribution and
      numerically by direct simulations. The model is found to exhibit long-lived
      nonmagnetized quasistationary states (QSSs) which in the thermodynamic limit are
      dynamically stable within an energy range where the equilibrium state is
      magnetized. For finite N, these states relax to equilibrium over a time that
      increases algebraically with N. In the dynamically unstable regime, nonmagnetized
      states relax fast to equilibrium over a time that scales as lnN. These features
      are retained in presence of a global anisotropy in the magnetization. 

PMID- 24329245
TI  - Interlayer-interaction dependence of latent heat in the Heisenberg model on a
      stacked triangular lattice with competing interactions.
AB  - We study the phase transition behavior of a frustrated Heisenberg model on a
      stacked triangular lattice by Monte Carlo simulations. The model has three types
      of interactions: the ferromagnetic nearest-neighbor interaction J(1) and
      antiferromagnetic third nearest-neighbor interaction J(3) in each triangular
      layer and the ferromagnetic interlayer interaction J([perpendicular]).
      Frustration comes from the intralayer interactions J(1) and J(3). We focus on the
      case that the order parameter space is SO(3)*C(3). We find that the model
      exhibits a first-order phase transition with breaking of the SO(3) and C(3)
      symmetries at finite temperature. We also discover that the transition
      temperature increases but the latent heat decreases as J([perpendicular])/J(1)
      increases, which is opposite to the behavior observed in typical unfrustrated
      three-dimensional systems.

PMID- 24329246
TI  - Analytic expression for the mean time to absorption for a random walker on the
      Sierpinski fractal. III. The effect of non-nearest-neighbor jumps.
AB  - We present exact, analytic results for the mean time to trapping of a random
      walker on the class of deterministic Sierpinski graphs embedded in d>=2 Euclidean
      dimensions, when both nearest-neighbor (NN) and next-nearest-neighbor (NNN) jumps
      are included. Mean first-passage times are shown to be modified significantly as
      a consequence of the fact that NNN transitions connect fractals of two
      consecutive generations. 

PMID- 24329247
TI  - Transport in weak dynamic disorder: a unified theory.
AB  - For quantum particles, it is well known that static disorder would lead to
      Anderson localization (AL) while dynamic (evolving) disorder would destroy AL and
      facilitate the transport. In this article, we study the transport behavior of a
      quantum particle in weak dynamic disorder. Based on Wigner representation, we
      obtain the radiative transfer equation (a linear Boltzmann equation) in the weak
      dynamic disorder limit, which could lead to not only all the existing transport
      behaviors in the literature but also new transport behaviors (for example, Levy
      flight in momentum space). Furthermore, for dimensions greater than one, though
      we can formally derive the diffusive transport approximation, we argue that this
      diffusive transport is not physical but the nondiffusive transport should persist
      forever. This provides a possible resolution for the long-standing puzzle whether
      diffusive or nondiffusive transport would prevail in the long time limit. Our
      result would have major implications for the hypertransport of light, matter wave
      dynamics in disordered media, and directed polymer problems. 

PMID- 24329248
TI  - Scaling behavior for random walks with memory of the largest distance from the
      origin.
AB  - We study a one-dimensional random walk with memory. The behavior of the walker is
      modified with respect to the simple symmetric random walk only when he or she is
      at the maximum distance ever reached from his or her starting point (home). In
      this case, having the choice to move farther or to move closer, the walker
      decides with different probabilities. If the probability of a forward step is
      higher then the probability of a backward step, the walker is bold, otherwise he
      or she is timorous. We investigate the asymptotic properties of this bold
      timorous random walk, showing that the scaling behavior varies continuously from
      subdiffusive (timorous) to superdiffusive (bold). The scaling exponents are fully
      determined with a new mathematical approach based on a decomposition of the
      dynamics in active journeys (the walker is at the maximum distance) and lazy
      journeys (the walker is not at the maximum distance). 

PMID- 24329249
TI  - Connection between maximum-work and maximum-power thermal cycles.
AB  - A new connection between maximum-power Curzon-Ahlborn thermal cycles and maximum
      work reversible cycles is proposed. This linkage is built through a mapping
      between the exponents of a class of heat transfer laws and the exponents of a
      family of heat capacities depending on temperature. This connection leads to the
      recovery of known results and to a wide and interesting set of results for a
      class of thermal cycles. Among other results it was found that it is possible to
      use analytically closed expressions for maximum-work efficiencies to calculate
      good approaches to maximum-power efficiencies. Behind the proposed connection is
      an interpretation of endoreversibility hypothesis. Additionally, we suggest that
      certain reversible maximum-work cycles depending on working substance can be used
      as reversible landmarks for FTT maximum-power cycles, which also depend on
      working substance properties. 

PMID- 24329250
TI  - Effects of nanoscale density inhomogeneities on shearing fluids.
AB  - It is well known that density inhomogeneities at the solid-liquid interface can
      have a strong effect on the velocity profile of a nanoconfined fluid in planar
      Poiseuille flow. However, it is difficult to control the density inhomogeneities
      induced by solid walls, making this type of system unsuitable for a comprehensive
      study of the effect on density inhomogeneity on nanofluidic flow. In this paper,
      we employ an external force compatible with periodic boundary conditions to
      induce the density variation, which greatly simplifies the problem when compared
      to flow in nonperiodic nanoconfined systems. Using the sinusoidal transverse
      force method to produce shearing velocity profiles and the sinusoidal
      longitudinal force method to produce inhomogeneous density profiles, we are able
      to observe the interactions between the two property inhomogeneities at the level
      of individual Fourier components. This gives us a method for direct measurement
      of the coupling between the density and velocity fields and allows us to
      introduce various feedback control mechanisms which customize fluid behavior in
      individual Fourier components. We briefly discuss the role of temperature
      inhomogeneity and consider whether local thermal expansion due to nonuniform
      viscous heating is sufficient to account for shear-induced density
      inhomogeneities. We also consider the local Newtonian constitutive relation
      relating the shear stress to the velocity gradient and show that the local model
      breaks down for sufficiently large density inhomogeneities over atomic length
      scales. 

PMID- 24329251
TI  - Monte Carlo simulation of classical spin models with chaotic billiards.
AB  - It has recently been shown that the computing abilities of Boltzmann machines, or
      Ising spin-glass models, can be implemented by chaotic billiard dynamics without
      any use of random numbers. In this paper, we further numerically investigate the
      capabilities of the chaotic billiard dynamics as a deterministic alternative to
      random Monte Carlo methods by applying it to classical spin models in statistical
      physics. First, we verify that the billiard dynamics can yield samples that
      converge to the true distribution of the Ising model on a small lattice, and we
      show that it appears to have the same convergence rate as random Monte Carlo
      sampling. Second, we apply the billiard dynamics to finite-size scaling analysis
      of the critical behavior of the Ising model and show that the phase-transition
      point and the critical exponents are correctly obtained. Third, we extend the
      billiard dynamics to spins that take more than two states and show that it can be
      applied successfully to the Potts model. We also discuss the possibility of
      extensions to continuous-valued models such as the XY model. 

PMID- 24329252
TI  - Temperature-dependent defect dynamics in the network glass SiO2.
AB  - We investigate the long time dynamics of a strong glass former, SiO(2), below the
      glass transition temperature by averaging single-particle trajectories over time
      windows which comprise roughly 100 particle oscillations. The structure on this
      coarse-grained time scale is very well defined in terms of coordination numbers,
      allowing us to identify ill-coordinated atoms, which are called defects in the
      following. The most numerous defects are O-O neighbors, whose lifetimes are
      comparable to the equilibration time at low temperature. On the other hand, SiO
      and OSi defects are very rare and short lived. The lifetime of defects is found
      to be strongly temperature dependent, consistent with activated processes. Single
      particle jumps give rise to local structural rearrangements. We show that in
      SiO(2) these structural rearrangements are coupled to the creation or
      annihilation of defects, giving rise to very strong correlations of jumping atoms
      and defects.

PMID- 24329253
TI  - Transport coefficients for driven granular mixtures at low density.
AB  - The transport coefficients of a granular binary mixture driven by a stochastic
      bath with friction are determined from the inelastic Boltzmann kinetic equation.
      A normal solution is obtained via the Chapman-Enskog method for states near
      homogeneous steady states. The mass, momentum, and heat fluxes are determined to
      first order in the spatial gradients of the hydrodynamic fields, and the
      associated transport coefficients are identified. They are given in terms of the
      solutions of a set of coupled linear integral equations. As in the monocomponent
      case, since the collisional cooling cannot be compensated for locally by the heat
      produced by the external driving, the reference distributions (zeroth-order
      approximations) f(i)((0)) (i=1,2) for each species depend on time through their
      dependence on the pressure and the temperature. Explicit forms for the diffusion
      transport coefficients and the shear viscosity coefficient are obtained by
      assuming the steady-state conditions and by considering the leading terms in a
      Sonine polynomial expansion. A comparison with previous results obtained for
      granular Brownian motion and by using a (local) stochastic thermostat is also
      carried out. The present work extends previous theoretical results derived for
      monocomponent dense gases [Garzo, Chamorro, and Vega Reyes, Phys. Rev. E 87,
      032201 (2013)] to granular mixtures at low density.

PMID- 24329254
TI  - Directed ratchet transport in granular chains.
AB  - Directed-ratchet transport (DRT) in a one-dimensional lattice of spherical beads,
      which serves as a prototype for granular chains, is investigated. We consider a
      system where the trajectory of the central bead is prescribed by a biharmonic
      forcing function with broken time-reversal symmetry. By comparing the mean
      integrated force of beads equidistant from the forcing bead, two distinct types
      of directed transport can be observed-spatial and temporal DRT. Based on the
      value of the frequency of the forcing function relative to the cutoff frequency,
      the system can be categorized by the presence and magnitude of each type of DRT.
      Furthermore, we investigate and quantify how varying additional parameters such
      as the biharmonic weight affects DRT velocity and magnitude. Finally, friction is
      introduced into the system and is found to significantly inhibit spatial DRT. In
      fact, for sufficiently low forcing frequencies, the friction may even induce a
      switching of the DRT direction. 

PMID- 24329255
TI  - Effect of aspect ratio on the development of order in vibrated granular rods.
AB  - We investigate ordering of granular rods in a container subject to vibrations in
      a gravitational field as a function of number density of the rods. We study rods
      with three different length to diameter aspect ratios A(r)= 5, 10, and 15. The
      measurements are performed in three dimensions using x-ray computer tomography to
      visualize the rods in the entire container. We first discuss a method to extract
      the position and orientation of the rods from the scans which enables us to
      obtain statistical measures of the degree of order in the packing. We find that
      the rods with A(r)=5 phase separate into domains with vertical and horizontal
      orientation as the number density of the rods is increased, whereas, for A(r)=10
      and 15 the rods are predominately oriented vertically in layers. By calculating
      two-point spatial correlation functions, we further show that long range
      hexagonal order occurs within a layer when the rods are oriented along the
      vertical axis. Thus, our experiments find that long range order increases rapidly
      in granular rods with growing anisotropy.

PMID- 24329256
TI  - Hydrodynamics of granular gases with a two-peak distribution.
AB  - Vibrating walls, frequently employed to maintain the temperature (i.e., average
      velocity) in a granular gas, modify the system strongly, rendering it dissimilar
      to a molecular one in various aspects. As evidenced by microgravity experiments
      employing a quasi-two-dimensional (quasi-2D) rectangular box and by 2D
      simulations, the one-peak velocity distribution is split into two, rendering the
      stress both nonuniform and anisotropic-without a shear flow and in the absence of
      gravitation. To account for this, granular hydrodynamics (as first proposed by
      Haff and later derived employing the kinetic theory) is generalized by
      introducing two additional variables, with one accounting for the distance
      between the two peaks and a second for the difference between the average
      velocities along different directions. The hydrodynamic theory thus generalized
      relates the velocity distribution to the stress, yielding results that agree with
      experiments and simulations. 

PMID- 24329257
TI  - Particle-scale reversibility in athermal particulate media below jamming.
AB  - We perform numerical simulations of repulsive, frictionless athermal disks in two
      and three spatial dimensions undergoing cyclic quasistatic simple shear to
      investigate particle-scale reversible motion. We identify three classes of steady
      state dynamics as a function of packing fraction phi and maximum strain amplitude
      per cycle gamma(max). Point-reversible states, where particles do not collide and
      exactly retrace their intracycle trajectories, occur at low phi and gamma(max).
      Particles in loop-reversible states undergo numerous collisions and execute
      complex trajectories but return to their initial positions at the end of each
      cycle. For sufficiently large phi and gamma(max), systems display irreversible
      dynamics with nonzero self-diffusion. Loop-reversible dynamics enables the
      reliable preparation of configurations with specified structural and mechanical
      properties over a broad range of phi.

PMID- 24329258
TI  - Sedimentation stability and aging of aqueous dispersions of Laponite in the
      presence of cetyltrimethylammonium bromide.
AB  - This work discusses the sedimentation stability and aging of aqueous suspensions
      of Laponite in the presence of cetyltrimethylammonium bromide (CTAB). The
      concentration of Laponite was fixed at a constant level C(l)=2%wt, which
      corresponds to the threshold between equilibrium gel IG(1) and glass IG(2)
      states. The concentration of CTAB C(s) was within 0-0.3 %wt. In the presence of
      CTAB, the Laponite aqueous suspensions were unstable against sedimentation and
      separated into the upper and bottom layers (U and B layers, respectively). The
      dynamic light-scattering technique has revealed that addition of CTAB even at a
      rather small concentration, C(s)=0.0164 %wt (0.03 cation exchange capacity),
      induced noticeable changes in the aging dynamics of the U layer. It was explained
      by equilibration of CTAB molecules that were initially nonuniformly distributed
      between different Laponite particles. Accelerated stability analysis by means of
      analytical centrifugation with rotor speed omega=500-4000 rpm revealed three
      sedimentation regimes: continuous (I, C(s)<0.14 %wt), zonelike (II,
      0.14<C(s)<0.2%wt), and gel-like (III, C(s)>0.2%wt). It was demonstrated that the
      B layer was "soft" in the zonelike regime. The increase of omega resulted in its
      supplementary compressing and collapse of "soft" sediment above certain critical
      centrifugal acceleration. The physical nature of the observed behavior,
      accounting for enhancement of hydrophobic interactions between Laponite
      particles, is discussed.

PMID- 24329259
TI  - Intrinsic viscosity of a suspension of cubes.
AB  - We report on the viscosity of a dilute suspension of cube-shaped particles.
      Irrespective of the particle size, size distribution, and surface chemistry, we
      find empirically that cubes manifest an intrinsic viscosity [eta]=3.1+/-0.2,
      which is substantially higher than the well-known value for spheres, [eta]=2.5.
      The orientation-dependent intrinsic viscosity of cubic particles is determined
      theoretically using a finite-element solution of the Stokes equations. For
      isotropically oriented cubes, these calculations show [eta]=3.1, in excellent
      agreement with our experimental observations. 

PMID- 24329260
TI  - Generalization of the Gouy-Chapman-Stern model of an electric double layer for a
      morphologically complex electrode: deterministic and stochastic morphologies.
AB  - We generalize the linearized Gouy-Chapman-Stern theory of an electric double
      layer for morphologically complex and disordered electrodes. An equation for
      capacitance is obtained using a linear Gouy-Chapman or Debye-Huckel equation for
      the potential near the complex-geometry electrode-electrolyte interface. The
      effect of the surface morphology of an electrode on an electric double layer is
      obtained using multiple scattering formalism in surface curvature. The result for
      capacitance is expressed in terms of the ratio of Gouy screening length to the
      local principal radii of curvatures of the surface. We also include a
      contribution of a compact layer, which is significant in the overall prediction
      of capacitance. Our general results are analyzed in detail for two special
      morphologies of electrodes, i.e., a nanoporous membrane and a forest of
      nanopillars. Variations of local shapes and global size variations due to
      residual randomness in morphology are accounted for as curvature fluctuations
      over a reference shape element. In particular, the theory shows that the presence
      of geometrical fluctuations in porous systems causes an enhanced dependence of
      capacitance on mean pore sizes and suppresses the magnitude of capacitance. This
      theory is further extended to include contributions to capacitance from
      adsorption of ions and electrode material due to electronic screening. Our
      predictions are in reasonable agreement with recent experimental measurements on
      supercapacitive microporous and mesoporous systems. 

PMID- 24329261
TI  - Nanometer-scale water droplet free from the constraint of reverse micelles at low
      temperatures.
AB  - Temperature dependence of the configurational fluctuation of water confined in a
      reverse micellar solution has been studied by absorption spectroscopy of a probe
      molecule. We have found that the configurational fluctuation is liquidlike below
      the homogeneous nucleation temperature. This is proposed to be due to a large
      reduction in the confinement of water, and is explained in terms of water
      shedding from the reverse micelle. Further, the configurational fluctuation is
      frozen at ~210 K. A reverse micellar solution is considered to be a promising
      candidate for studies of supercooled water.

PMID- 24329262
TI  - Yield stress in amorphous solids: a mode-coupling-theory analysis.
AB  - The yield stress is a defining feature of amorphous materials which is difficult
      to analyze theoretically, because it stems from the strongly nonlinear response
      of an arrested solid to an applied deformation. Mode-coupling theory predicts the
      flow curves of materials undergoing a glass transition and thus offers
      predictions for the yield stress of amorphous solids. We use this approach to
      analyze several classes of disordered solids, using simple models of hard-sphere
      glasses, soft glasses, and metallic glasses for which the mode-coupling
      predictions can be directly compared to the outcome of numerical measurements.
      The theory correctly describes the emergence of a yield stress of entropic nature
      in hard-sphere glasses, and its rapid growth as density approaches random close
      packing at qualitative level. By contrast, the emergence of solid behavior in
      soft and metallic glasses, which originates from direct particle interactions is
      not well described by the theory. We show that similar shortcomings arise in the
      description of the caging dynamics of the glass phase at rest. We discuss the
      range of applicability of mode-coupling theory to understand the yield stress and
      nonlinear rheology of amorphous materials. 

PMID- 24329263
TI  - Anisotropic dynamics of water ultraconfined in macroscopically oriented channels
      of single-crystal beryl: a multifrequency analysis.
AB  - The properties of fluids can be significantly altered by the geometry of their
      confining environments. While there has been significant work on the properties
      of such confined fluids, the properties of fluids under ultraconfinement,
      environments where, at least in one plane, the dimensions of the confining
      environment are similar to that of the confined molecule, have not been
      investigated. This paper investigates the dynamic properties of water in beryl
      (Be(3)Al(2)Si(6)O(18)), the structure of which contains approximately 5-A-diam
      channels parallel to the c axis. Three techniques, inelastic neutron scattering,
      quasielastic neutron scattering, and dielectric spectroscopy, have been used to
      quantify these properties over a dynamic range covering approximately 16 orders
      of magnitude. Because beryl can be obtained in large single crystals we were able
      to quantify directional variations, perpendicular and parallel to the channel
      directions, in the dynamics of the confined fluid. These are significantly
      anisotropic and, somewhat counterintuitively, show that vibrations parallel to
      the c-axis channels are significantly more hindered than those perpendicular to
      the channels. The effective potential for vibrations in the c direction is harder
      than the potential in directions perpendicular to it. There is evidence of single
      file diffusion of water molecules along the channels at higher temperatures, but
      below 150 K this diffusion is strongly suppressed. No such suppression, however,
      has been observed in the channel-perpendicular direction. Inelastic neutron
      scattering spectra include an intramolecular stretching O-H peak at ~465 meV. As
      this is nearly coincident with that known for free water molecules and
      approximately 30 meV higher than that in liquid water or ice, this suggests that
      there is no hydrogen bonding constraining vibrations between the channel water
      and the beryl structure. However, dielectric spectroscopic measurements at higher
      temperatures and lower frequencies yield an activation energy for the dipole
      reorientation of 16.4 +/- 0.14 kJ/mol, close to the energy required to break a
      hydrogen bond in bulk water. This may suggest the presence of some other form of
      bonding between the water molecules and the structure, but the resolution of the
      apparent contradiction between the inelastic neutron and dielectric spectroscopic
      results remains uncertain.

PMID- 24329264
TI  - Nonequilibrium dynamics of a confined colloidal bilayer in a planar shear flow.
AB  - Using Brownian dynamics (BD) simulations we investigate the impact of shear flow
      on structural and dynamical properties of a system of charged colloids confined
      to a narrow slit pore. Our model consists of spherical microions interacting
      through a Derjaguin-Landau-Verwey-Overbeek (DLVO) and a soft-sphere potential.
      The DLVO parameters were chosen according to a system of moderately charged
      silica particles (with valence Z~35) in a solvent of low ionic strength. At the
      confinement conditions considered, the colloids form two well-pronounced layers.
      In the present study we investigate shear-induced transitions of the
      translational order and dynamics in the layers, including a discussion of the
      translational diffusion. In particular, we show that diffusion in the shear
      melted state can be described by an analytical model involving a single shear
      driven particle in a harmonic trap. We also explore the emergence of zigzag
      motion characterized by spatiotemporal oscillations of the particles in the
      layers in the vorticity direction. Similar behavior has been recently observed in
      experiments of much thicker colloidal films.

PMID- 24329265
TI  - Transient formation of bcc crystals in suspensions of poly(N-isopropylacrylamide)
      based microgels.
AB  - We present a small-angle x-ray scattering study of crystals formed by temperature
      sensitive, swollen microgel particles consisting of poly(N-isopropylacrylamide)
      copolymerized with acrylic acid and 5 mol % of a cross-linker. As for hard
      spheres, the random hexagonal close-packed structure is predominant during
      crystal growth and slowly transforms toward the face-centered-cubic structure.
      However, a transient phase of body-centered-cubic crystal is observed in an
      intermediate range of effective volume fractions. We estimate that the studied
      suspensions are close to a transition from face-centered-cubic to body-centered
      cubic structure that can be understood by the tendency of the system to maximize
      the excluded volume and minimize the contact area between the particles. 

PMID- 24329266
TI  - Understanding collective dynamics of soft active colloids by binary scattering.
AB  - Collective motion in actively propelled particle systems is triggered on the very
      local scale by nucleation of coherently moving units consisting of just a handful
      of particles. These units grow and merge over time, ending up in a long-range
      ordered, coherently moving state. So far, there exists no bottom-up understanding
      of how the microscopic dynamics and interactions between the constituents are
      related to the system's ordering instability. In this paper, we study a class of
      models for propelled colloids allowing an explicit treatment of the microscopic
      details of the collision process. Specifically, the model equations are Newtonian
      equations of motion with separate force terms for particles' driving,
      dissipation, and interaction forces. Focusing on dilute particle systems, we
      analyze the binary scattering behavior for these models and determine-based on
      the microscopic dynamics-the corresponding "collision rule," i.e., the mapping of
      precollisional velocities and impact parameter on postcollisional velocities. By
      studying binary scattering we also find that the considered models for active
      colloids share the same principle for parallel alignment: The first incoming
      particle (with respect to the center of collision) is aligned to the second
      particle as a result of the encounter. This behavior distinctively differs from
      alignment in nondriven dissipative gases. Moreover, the obtained collision rule
      lends itself as a starting point to apply kinetic theory for propelled particle
      systems in order to determine the phase boundary to a long-range ordered,
      coherently moving state. The microscopic origin of the collision rule offers the
      opportunity to quantitatively scrutinize the predictions of kinetic theory for
      propelled particle systems through direct comparison with multiparticle
      simulations. We identify local precursor correlations at the onset of collective
      motion to constitute the essential determinant for a qualitative and quantitative
      validity of kinetic theory. In conclusion, our "renormalized" approach clearly
      indicates that the framework of kinetic theory is flexible enough to accommodate
      the complex behavior of soft active colloids and allows a bottom-up understanding
      of how the microscopic dynamics of binary collisions relates to the system's
      behavior on large length and time scales. 

PMID- 24329267
TI  - Kinetics of anisotropic ordering in Laponite dispersions induced by a water-air
      interface.
AB  - In this work, we report the kinetics of ordering occurring at the water-air
      interface of Laponite dispersions. Propagation of such ordering into the bulk and
      its relaxation dynamics were systematically studied through light scattering
      measurements. Depolarization ratio D(p), which accounted for the optical
      anisotropy, was measured as a function of depth from the interface and aging of
      the samples. The extent of spatial ordering was found to be several decades
      larger than the typical particle size. Spatial ordering originated from the
      interface and percolated into the bulk with aging time t(w). Growth in D(p) with
      waiting time was found to follow power-law behavior given as D(p)~t(w)(n), with n
      increasing from 0.1 to 4 as one moved away from the interface into the bulk. D(p)
      decreased exponentially with depth h given as D(p)~e(-(h/h(0))), where h(0) is
      the decay length, increasing from 0.4 to 0.75 mm with aging time. Dynamic
      structure factor measurements performed on the samples at various aging times,
      depths, and temperatures yielded two distinct relaxation times: one fast mode
      followed by a slow mode. The fast mode remained invariant while slow mode
      relaxation time followed an exponential decay with depth. This study indicated
      that the arrested phase nucleated from the interface and propagated into the
      bulk, which was not observed when the surface was insulated with a layer of
      hydrophobic liquid. Dilution of the concentrated samples destroyed the aforesaid
      ordering and made the dispersion homogeneous implying the ordered state was a
      glass.

PMID- 24329268
TI  - Computational study of the propagation of the longitudinal velocity in a polymer
      melt contained within a cylinder using a scale-bridging method.
AB  - The "constitutive equation"-free scale-bridging method connecting nonequilibrium
      molecular dynamics and continuum fluid mechanics, that had hitherto been applied
      only to a parallel-plates geometry, is extended to study the flow of a polymer
      melt in a cylindrical pipe subject to a velocity in the direction parallel to the
      cylinder's axis. The system, initially at rest, is given a velocity at the
      cylinder's surface, and the evolution of the velocity profile within the fluid is
      studied, along with the time taken for the velocity to propagate toward the
      cylinder's axis. The said time of propagation is found to increase with the
      boundary velocity-a fact in contrast with the case of a Newtonian fluid for which
      the time of propagation is expected to be independent of the boundary velocity.
      For a fixed value of the boundary velocity, the propagation time is found to
      increase with the cylinder radius according to a power law with an exponent that
      is smaller than the corresponding exponent for a Newtonian fluid. For the lower
      values of the boundary velocity and the lower values of the radius studied, a
      velocity overshoot is observed at the cylinder's axis-a manifestation of elastic
      behavior of the fluid. 

PMID- 24329269
TI  - Impedance spectroscopy of ions at liquid-liquid interfaces.
AB  - The possibility to extract properties of an interface between two immiscible
      liquids, e.g., electrolyte solutions or polyelectrolyte multilayers, by means of
      impedance spectroscopy is investigated theoretically within a dynamic density
      functional theory which is equivalent to the Nernst-Planck-Poisson theory. An
      approach based on a two-step fitting procedure of an equivalent circuit to
      impedance spectra is proposed which allows us to uniquely separate bulk and
      interfacial elements. Moreover, the proposed method avoids overfitting of the
      bulk properties of the two liquids in contact and underfitting of the interfacial
      properties, as they might occur for standard one-step procedures. The key idea is
      to determine the bulk elements of the equivalent circuit in a first step by
      fitting corresponding subcircuits to the spectra of uniform electrolyte
      solutions, and afterwards fitting the full equivalent circuit with fixed bulk
      elements to the impedance spectrum containing the interface. This approach is
      exemplified for an equivalent circuit which leads to a physically intuitive
      qualitative behavior as well as to quantitatively realistic values of the
      interfacial elements. The proposed method is robust such that it can be expected
      to be applicable to a wide class of systems with liquid-liquid interfaces. 

PMID- 24329270
TI  - Length-scale crossover of the hydrophobic interaction in a coarse-grained water
      model.
AB  - It has been difficult to establish a clear connection between the hydrophobic
      interaction among small molecules typically studied in molecular simulations (a
      weak, oscillatory force) and that found between large, macroscopic surfaces in
      experiments (a strong, monotonic force). Here, we show that both types of
      interaction can emerge with a simple, core-softened water model that captures
      water's unique pairwise structure. As in hydrophobic hydration, we find that the
      hydrophobic interaction manifests a length-scale dependence, exhibiting distinct
      driving forces in the molecular and macroscopic regimes. Moreover, the ability of
      this simple model to capture both regimes suggests that several features of the
      hydrophobic force can be understood merely through water's pair correlations. 

PMID- 24329271
TI  - Effects of viscosity, surface tension, and evaporation rate of solvent on dry
      colloidal structures: a lattice Boltzmann study.
AB  - Understanding the mechanisms of how colloidal solution properties and drying
      processes result in dry colloidal structures is essential for industrial
      applications such as paint, ceramics, and electrodes. In this study, we develop a
      computational method to simulate the drying process of colloidal suspensions
      containing solid particles and polymers. The method consists of a solvent
      evaporation model, a fluid particle dynamics method, and a two-phase lattice
      Boltzmann method. We determine that a high-viscosity solvent, small surface
      tension, and a high evaporation rate of the solvent lead to a structure with
      dispersed particles and interconnected pores. When these conditions are not
      present, the particles agglomerate and the pores are disconnected. 

PMID- 24329272
TI  - Limiting law excess sum rule for polyelectrolytes.
AB  - We revisit the mean-field limiting law screening excess sum rule that holds for
      rodlike polyelectrolytes. We present an efficient derivation of this law that
      clarifies its region of applicability: The law holds in the limit of small
      polymer radius, measured relative to the Debye screening length. From the
      limiting law, we determine the individual ion excess values for single-salt
      electrolytes. We also consider the mean-field excess sum away from the limiting
      region, and we relate this quantity to the osmotic pressure of a dilute
      polyelectrolyte solution. Finally, we consider numerical simulations of many-body
      polymer-electrolyte solutions. We conclude that the limiting law often accurately
      describes the screening of physical charged polymers of interest, such as
      extended DNA. 

PMID- 24329273
TI  - Friction of viscoelastic elastomers with rough surfaces under torsional contact
      conditions.
AB  - Frictional properties of contacts between a smooth viscoelastic rubber and rigid
      surfaces are investigated using a torsional contact configuration where a glass
      lens is continuously rotated on the rubber surface. From the inversion of the
      displacement field measured at the surface of the rubber, spatially resolved
      values of the steady state frictional shear stress are determined within the
      nonhomogeneous pressure and velocity fields of the contact. For contacts with a
      smooth lens, a velocity-dependent but pressure-independent local shear stress is
      retrieved from the inversion. On the other hand, the local shear stress is found
      to depend on both velocity and applied contact pressure when a randomly rough
      (sand-blasted) glass lens is rubbed against the rubber surface. As a result of
      changes in the density of microasperity contacts, the amount of light transmitted
      by the transparent multicontact interface is observed to vary locally as a
      function of both contact pressure and sliding velocity. Under the assumption that
      the intensity of light transmitted by the rough interface is proportional to the
      proportion of area into contact, it is found that the local frictional stress can
      be expressed experimentally as the product of a purely velocity-dependent term,
      k(v), by a term representing the pressure and velocity dependence of the actual
      contact area, A/A(0). A comparison between k(v) and the frictional shear stress
      of smooth contacts suggests that nanometer scale dissipative processes occurring
      at the interface predominate over viscoelastic dissipation at microasperity
      scale.

PMID- 24329274
TI  - Stability and roughness of tensile cracks in disordered materials.
AB  - We study the stability and roughness of propagating cracks in heterogeneous
      brittle two-dimensional elastic materials. We begin by deriving an equation of
      motion describing the dynamics of such a crack in the framework of linear elastic
      fracture mechanics, based on the Griffith criterion and the principle of local
      symmetry. This result allows us to extend the stability analysis of Cotterell and
      Rice [B. Cotterell and J. R. Rice, Int. J. Fract. 16, 155 (1980)] to disordered
      materials. In the stable regime we find stochastic crack paths. Using tools of
      statistical physics, we obtain the power spectrum of these paths and their
      probability distribution function and conclude that they do not exhibit self
      affinity. We show that a real-space fractal analysis of these paths can lead to
      the wrong conclusion that the paths are self-affine. To complete the picture, we
      unravel a systematic bias in such real-space methods and thus contribute to the
      general discussion of reliability of self-affine measurements. 

PMID- 24329275
TI  - Electrodynamic interaction between a nanoparticle and the surface of a solid.
AB  - We study the interaction between a nanoparticle and the surface of a solid in the
      framework of the local-field method. Assuming that the nanoparticle is
      characterized by a finite nonlinear polarizability, we obtain the interaction
      potential that is repulsive at short range and has an attractive long-range tail.
      Our numerical analysis shows that this potential strongly depends on the shape
      and size of the particle. Further, we study the particle-surface interaction in
      the presence of a surface plasmon polariton propagating along the interface. It
      is shown that the excitation of the surface wave leads to a drastic (about one
      order of magnitude) increase in the binding energy. Potential applications of
      this effect are discussed. 

PMID- 24329276
TI  - Shape transitions in soft spheres regulated by elasticity.
AB  - We study elasticity-driven morphological transitions of soft spherical core-shell
      structures in which the core can be treated as an isotropic elastic continuum and
      the surface or shell as a tensionless liquid layer, whose elastic response is
      dominated by bending. To generate the transitions, we consider the case where the
      surface area of the liquid layer is increased for a fixed amount of interior
      elastic material. We find that generically there is a critical excess surface
      area at which the isotropic sphere becomes unstable to buckling. At this point it
      adopts a lower symmetry wrinkled structure that can be described by a spherical
      harmonic deformation. We study the dependence of the buckled sphere and critical
      excess area of the transition on the elastic parameters and size of the system.
      We also relate our results to recent experiments on the wrinkling of gel-filled
      vesicles as their interior volume is reduced. The theory may have broader
      applications to a variety of related structures from the macroscopic to the
      microscopic, including the wrinkling of dried peas, raisins, as well as the cell
      nucleus. 

PMID- 24329277
TI  - Inclined fluid-film flow with bottom filtration.
AB  - We investigate the interfacial instability of the steady uniform flow of a fluid
      film layer down a permeable incline. A theoretical model is obtained by coupling
      the clear fluid flow equations governing the fluid film with Darcy's law for the
      filtration of fluid through the porous medium. A linear stability analysis is
      conducted and the effect of various parameters on the state of neutral stability
      is investigated. A simplified model is developed by reducing the dimensionality
      of the problem, which is then employed in order to determine the nonlinear
      effects on the stability of the equilibrium flow. 

PMID- 24329278
TI  - Traction and nonequilibrium phase behavior of confined sheared liquids at high
      pressure.
AB  - Nonequilibrium molecular dynamics simulations of confined model liquids under
      pressure and sheared by the relative sliding of the boundary walls have been
      carried out. The relationship between the time-dependent traction coefficient,
      MU(t), and the state of internal structure of the film is followed from
      commencement of shear for various control parameters, such as applied load,
      global shear rate, and solid-liquid atom interaction parameters. Phase diagrams,
      velocity and temperature profiles, and traction coefficient diagrams are analyzed
      for pure Lennard-Jones (LJ) liquids and a binary LJ mixture. A single component
      LJ liquid is found to form semicrystalline arrangements with high-traction
      coefficients, and stick-slip behavior is observed for high pressures and low
      shear velocities, which is shown to involve periodic deformation and stress
      release of the wall atoms and slip in the solid-liquid boundary region. A binary
      mixture, which discourages crystallization, gives a more classical tribological
      response with the larger atoms preferentially adsorbing commensurate with the
      wall. The results obtained are analyzed in the context of tribology: the binary
      mixture behaves like a typical lubricant, whereas the monatomic system behaves
      like a traction fluid. It is discussed how this type of simulation can give
      insights on the tribological behavior of realistic systems. 

PMID- 24329279
TI  - Influence of nonuniform surface magnetic fields in wetting transitions in a
      confined two-dimensional Ising ferromagnet.
AB  - Wetting transitions are studied in the two-dimensional Ising ferromagnet confined
      between walls where competitive surface fields act. In our finite samples of size
      L*M, the walls are separated by a distance L, M being the length of the sample.
      The surface fields are taken to be short-range and nonuniform, i.e., of the form
      H(1),deltaH(1),H(1),deltaH(1),..., where the parameter -1<=delta<=1 allows us to
      control the nonuniformity of the fields. By performing Monte Carlo simulations we
      found that those competitive surface fields lead to the occurrence of an
      interface between magnetic domains of different orientation that runs parallel to
      the walls. In finite samples, such an interface undergoes a localization
      delocalization transition, which is the precursor of a true wetting transition
      that takes place in the thermodynamic limit. By exactly working out the ground
      state (T=0), we found that besides the standard nonwet and wet phases, a surface
      antiferromagnetic-like state emerges for delta<-1/3 and large fields (H(1)>3),
      H(1)(tr)/J=3, delta(tr)=-1/3,T=0, being a triple point where three phases
      coexist. By means of Monte Carlo simulations it is shown that these features of
      the phase diagram remain at higher temperatures; e.g., we examined in detail the
      case T=0.7*T(cb). Furthermore, we also recorded phase diagrams for fixed values
      of delta, i.e., plots of the critical field at the wetting transition (H(1w))
      versus T showing, on the one hand, that the exact results of Abraham [Abraham,
      Phys. Rev. Lett. 44, 1165 (1980)] for delta=1 are recovered, and on the other
      hand, that extrapolations to T->0 are consistent with our exact results. Based on
      our numerical results we conjectured that the exact result for the phase diagram
      worked out by Abraham can be extended for the case of nonuniform fields. In fact,
      by considering a nonuniform surface field of some period lambda, with lambda<<M,
      e.g., [H(1)(x,lambda)>0], one can obtain the effective field H(eff) at a lambda
      coarse-grained level given by H(eff)=1/lambda?(x=1)(lambda)H(1)(x,lambda). Then
      we conjectured that the exact solution for the phase diagram is now given by
      H(eff)/J=F(T), where F(T) is a function of the temperature T that
      straightforwardly follows from Abraham's solution. The conjecture was
      exhaustively tested by means of computer simulations. Furthermore, it is found
      that for delta?1 the nonwet phase becomes enlarged, at the expense of the wet
      one, i.e., a phenomenon that we call "surface nonuniformity-induced nonwetting,"
      similar to the already known case of "roughness-induced nonwetting."

PMID- 24329280
TI  - Scaling and width distributions of parity-conserving interfaces.
AB  - We present an alternative finite-size approach to a set of parity-conserving
      interfaces involving attachment, dissociation, and detachment of extended objects
      in 1+1 dimensions. With the aid of a nonlocal construct introduced by Barma and
      Dhar in related systems [Phys. Rev. Lett. 73, 2135 (1994)], we circumvent the
      subdiffusive dynamics and examine close-to-equilibrium aspects of these
      interfaces by assembling states of much smaller, numerically accessible scales.
      As a result, roughening exponents, height correlations, and width distributions
      exhibiting universal scaling functions are evaluated for interfaces virtually
      grown out of dimers and trimers on large-scale substrates. Dynamic exponents are
      also studied by finite-size scaling of the spectrum gaps of evolution operators. 

PMID- 24329281
TI  - Phase-field modeling of two-dimensional crystal growth with anisotropic
      diffusion.
AB  - In the present article, we introduce a phase-field model for thin-film growth
      with anisotropic step energy, attachment kinetics, and diffusion, with second
      order (thin-interface) corrections. We are mainly interested in the limit in
      which kinetic anisotropy dominates, and hence we study how the expected shape of
      a crystallite, which in the long-time limit is the kinetic Wulff shape, is
      modified by anisotropic diffusion. We present results that prove that anisotropic
      diffusion plays an important, counterintuitive role in the evolving crystal
      shape, and we add second-order corrections to the model that provide a
      significant increase in accuracy for small supersaturations. We also study the
      effect of different crystal symmetries and discuss the influence of the
      deposition rate. 

PMID- 24329282
TI  - Structure transitions in oblate nematic droplets.
AB  - We consider the structure transitions in oblate supramicrometer nematic droplets
      related to reorientation of the line defect in the electric field. These
      transitions can be used in optical devices based on polymer dispersed liquid
      crystal materials with high contrast ratio. We suggest a simple method for
      determination of director distribution in nematic droplets of an arbitrary shape
      with surface interaction and in the presence of constant electric field. Point
      and linear defects are taken into account. This method does not require any
      presuppositions about symmetry of the director distribution. The elasticity
      continuum theory is treated with Monte Carlo annealing on a simple lattice. A
      special triangulation-based technique is applied for accurate representation of
      the droplet boundaries. The method is tested on 5CB material. 

PMID- 24329283
TI  - Peculiarity of the interaction of small particles in smectic liquid crystals.
AB  - We investigate the peculiarity of the interaction between particles immersed into
      a smectic liquid crystal with a layered structure. Such a structure of a liquid
      crystal imposes restrictions on possible deformations of the layer displacement
      field. Previous studies neglect this fact and give improper results for the
      interaction potential within one molecular layer. The present paper shows that
      such restrictions yield an interaction potential substantially different from
      those of previous studies. Oscillatory behavior, which was not present in the
      potentials of previous studies, might give rise to superstructures of immersed
      particles with finite interparticle distance. 

PMID- 24329284
TI  - Magnetically induced bistable behavior of ferronematic liquid crystals.
AB  - In the framework of the modified model [S. V. Burylov and A. N. Zakhlevnykh,
      Phys. Rev. E 88, 012511 (2013)] of soft ferronematic liquid crystals, i.e.,
      suspensions of needlelike ferroparticles in nematic solvents, we consider the
      ferronematic states with different mutual orientations of the director and
      magnetization. We study the transitions between states in an external magnetic
      field and show that these transitions are characterized by either continuous or
      discontinuous changes in the order parameter; i.e., they can be both the second
      order and the first-order, respectively. In the latter case the magnetic field
      induced orientational hysteresis arises, which can be observed in experiments on
      the birefringence of ferronematic liquid crystals. 

PMID- 24329285
TI  - Two-dimensional system of hard ellipses: a molecular dynamics study.
AB  - We have simulated the dynamics of a two-dimensional system of hard ellipses by
      event-oriented molecular dynamics in microcanonical NVE ensemble. Various
      quantities, namely longitudinal and transverse velocity auto-correlation
      functions, translational and rotational diffusion mean-squared displacements,
      pressure, intermediate self-scattering function, radial distribution function,
      and angular spatial correlation, have been obtained and their dependence on
      packing fraction is characterized. Despite absence of prominent positional
      ordering, the orientational degree of freedom behaves nontrivially and exhibits
      interesting features. Slowing down is observed in the angular part of the motion
      near isotropic-nematic phase transition. It is shown that above a certain packing
      fraction the rotational mean-squared displacement exhibits a three-stage temporal
      regime including a plateau. Comparison to 2D system of hard needles is made and
      it is shown that from positional viewpoint, the ellipse system is more ordered. 

PMID- 24329286
TI  - Normal stresses in elastic networks.
AB  - When loaded in simple shear deformation, polymeric materials may develop so
      called normal stresses: stresses perpendicular to the direction of the applied
      shear. These normal stresses are intrinsically nonlinear: basic symmetry
      considerations dictate they may only enter at O(gamma(2)), with gamma the
      dimensionless shear strain. There is no fundamental restriction on their sign,
      and normal stresses may be positive (pushing outward) or negative (pulling
      inward). Most materials tend to dilate in the normal direction, but a wide
      variety of biopolymer networks including fibrin and actin gels have been reported
      to present anomalously large, negative normal stresses-a feature which has been
      ascribed to the intrinsic elastic nonlinearity of semiflexible fibers. In this
      work, we present analytical results on a model nonlinear network, which we expand
      to the required nonlinear order to show that due to geometric, rather than
      elastic, nonlinearities (negative) normal stresses generically arise in
      filamentous networks-even in networks composed of linear, Hookean springs. We
      investigate analytically and numerically how the subsequent addition of elastic
      nonlinearities, nonaffine deformations, and filament persistence through cross
      linkers augment this basic behavior.

PMID- 24329287
TI  - Superionic behavior in polyethylene-oxide-based single-ion conductors.
AB  - We demonstrate superionic ion conduction in simulations of a poly(ethylene oxide)
      based polymer electrolyte. The superionic conduction uses cation hopping via
      chain-like ion aggregates, enabling long-range charge transfer while ions only
      move locally. The Na single-ion conductor achieves two essential features of
      superionic metal ion conductors: one-dimensional ion structure and immobile
      anions. The superionic conduction depends on the number and length of conduction
      pathways, the conduction pathway lifetime, and the rate at which end ions join
      and leave the pathway. 

PMID- 24329288
TI  - Tensorial conservation law for nematic polymers.
AB  - We derive the "conservation law" for nematic polymers in tensorial form valid for
      quadrupolar orientational order, in contradistinction to the conservation law in
      the case of polar orientational order. Due to microscopic differences in the
      coupling between the orientational field deformations and the density variations
      for polar and quadrupolar order, we find that the respective order parameters
      satisfy fundamentally distinct constraints. Being necessarily scalar in its form,
      the tensorial conservation law is obtained straightforwardly from the gradients
      of the polymer nematic tensor field and connects the spatial variation of this
      tensor field with density variations. We analyze the differences between the
      polar and the tensorial forms of the conservation law, present some explicit
      orientational fields that satisfy the tensorial constraint, and discuss the role
      of singular "hairpins," which do not affect the local quadrupolar order of
      polymer nematics, but nevertheless influence its gradients. 

PMID- 24329289
TI  - Polymer model with long-range interactions: analysis and applications to the
      chromatin structure.
AB  - Chromatin inside the cell nucleus consists of the DNA and its hierarchy of
      interacting molecules, which can be modeled as a complex polymer. To describe the
      chromatin dynamic, we develop and analyze here a polymer model that accounts for
      long-range interactions and not just those between the closest neighbors as in
      the Rouse polymer model. Our construction of the polymer model allows us to
      recover the local interaction between monomers from the anomalous diffusion
      exponent, which can be directly measured experimentally. We compute
      asymptotically for this polymer model the cross-correlation function for a given
      monomer and the mean time for a loop to be formed. Finally, we discuss some
      possible applications for interpretation of chromosome capture data. 

PMID- 24329290
TI  - Kinetic Monte Carlo approach to RNA folding dynamics using structure-based
      models.
AB  - RNA molecules form three-dimensional structures via base pairing that determine
      the function and biochemical activity of the molecule. Here we introduce a
      structure-based method for studying the folding dynamics of RNA secondary
      structures. The approach focuses on native contacts that are parametrized with
      standard empirical free energies. Kinetic Monte Carlo simulations for free
      folding of simple hairpins and complex structures such as a tRNA as well as for
      folding in the presence of an external force show good agreement with
      experimental data. A systematic comparison of simulated and experimental folding
      rates for various structures shows a strong correlation, indicating that the
      approach can predict folding rates within about an order of magnitude. 

PMID- 24329291
TI  - Cellular senescence in the Penna model of aging.
AB  - Cellular senescence is thought to play a major role in age-related diseases,
      which cause nearly 67% of all human deaths worldwide. Recent research in mice
      showed that exercising mice had higher levels of telomerase, an enzyme that helps
      maintain telomere length, than nonexercising mice. A commonly used model for
      biological aging was proposed by Penna. I propose a modification of the Penna
      model that incorporates cellular senescence and find an analytical steady-state
      solution following Coe, Mao, and Cates [Phys. Rev. Lett. 89, 288103 (2002)]. I
      find that models corresponding to delayed cellular senescence have younger
      populations that live longer. I fit the model to the United Kingdom's death
      distribution, which the original Penna model cannot do. 

PMID- 24329292
TI  - Effect of magnesium ions on dielectric relaxation in semidilute DNA aqueous
      solutions.
AB  - The effect of magnesium ion Mg(2+) on the dielectric relaxation of semidilute DNA
      aqueous solutions has been studied by means of dielectric spectroscopy in the 100
      Hz-100 MHz frequency range. de Gennes-Pfeuty-Dobrynin semidilute solution
      correlation length is the pertinent fundamental length scale for sufficiently low
      concentration of added salt, describing the collective properties of Mg-DNA
      solutions. No relaxation fingerprint of the DNA denaturation bubbles, leading to
      exposed hydrophobic core scaling, was detected at low DNA concentrations, thus
      indicating an increased stability of the double-stranded conformation in Mg-DNA
      solutions as compared to the case of Na-DNA solutions. Some changes are detected
      in the behavior of the fundamental length scale pertaining to the single molecule
      DNA properties, reflecting modified electrostatic screening effects of the Odijk
      Skolnick-Fixman type. All results consistently demonstrate that Mg(2+) ions
      interact with DNA in a similar way as Na(1+) ions do, their effect being mostly
      describable through an enhanced screening.

PMID- 24329293
TI  - Energy-landscape paving for prediction of face-centered-cubic hydrophobic
      hydrophilic lattice model proteins.
AB  - Protein structure prediction (PSP) is a classical NP-hard problem in
      computational biology. The energy-landscape paving (ELP) method is a class of
      heuristic global optimization algorithm, and has been successfully applied to
      solving many optimization problems with complex energy landscapes in the
      continuous space. By putting forward a new update mechanism of the histogram
      function in ELP and incorporating the generation of initial conformation based on
      the greedy strategy and the neighborhood search strategy based on pull moves into
      ELP, an improved energy-landscape paving (ELP+) method is put forward. Twelve
      general benchmark instances are first tested on both two-dimensional and three
      dimensional (3D) face-centered-cubic (fcc) hydrophobic-hydrophilic (HP) lattice
      models. The lowest energies by ELP+ are as good as or better than those of other
      methods in the literature for all instances. Then, five sets of larger-scale
      instances, denoted by S, R, F90, F180, and CASP target instances on the 3D FCC HP
      lattice model are tested. The proposed algorithm finds lower energies than those
      by the five other methods in literature. Not unexpectedly, this is particularly
      pronounced for the longer sequences considered. Computational results show that
      ELP+ is an effective method for PSP on the fcc HP lattice model. 

PMID- 24329294
TI  - Elastic response of filamentous networks with compliant crosslinks.
AB  - Experiments have shown that elasticity of disordered filamentous networks with
      compliant crosslinks is very different from networks with rigid crosslinks. Here,
      we model and analyze filamentous networks as a collection of randomly oriented
      rigid filaments connected to each other by flexible crosslinks that are modeled
      as wormlike chains. For relatively large extensions we allow for enthalpic
      stretching of crosslink backbones. We show that for sufficiently high crosslink
      density, the network linear elastic response is affine on the scale of the
      filaments' length. The nonlinear regime can become highly nonaffine and is
      characterized by a divergence of the elastic modulus at finite strain. In
      contrast to the prior predictions, we do not find an asymptotic regime in which
      the differential elastic modulus scales linearly with the stress, although an
      approximate linear dependence can be seen in a transition from entropic to
      enthalpic regimes. We discuss our results in light of recent experiments. 

PMID- 24329295
TI  - Long-time mean-square displacements in proteins.
AB  - We propose a method for obtaining the intrinsic, long-time mean square
      displacement (MSD) of atoms and molecules in proteins from finite-time molecular
      dynamics (MD) simulations. Typical data from simulations are limited to times of
      1 to 10 ns, and over this time period the calculated MSD continues to increase
      without a clear limiting value. The proposed method consists of fitting a model
      to MD simulation-derived values of the incoherent intermediate neutron scattering
      function, I(inc)(Q,t), for finite times. The infinite-time MSD, <r(2)>, appears
      as a parameter in the model and is determined by fits of the model to the finite
      time I(inc)(Q,t). Specifically, the <r(2)> is defined in the usual way in terms
      of the Debye-Waller factor as I(Q,t=infinity)=exp(-Q(2)<r(2)>/3). The method is
      illustrated by obtaining the intrinsic MSD <r(2)> of hydrated lysozyme powder
      (h=0.4 g water/g protein) over a wide temperature range. The intrinsic <r(2)>
      obtained from data out to 1 and to 10 ns is found to be the same. The intrinsic
      <r(2)> is approximately twice the value of the MSD that is reached in simulations
      after times of 1 ns which correspond to those observed using neutron instruments
      that have an energy resolution width of 1 MUeV.

PMID- 24329296
TI  - Interplay between single-stranded binding proteins on RNA secondary structure.
AB  - RNA-protein interactions control the fate of cellular RNAs and play an important
      role in gene regulation. An interdependency between such interactions allows for
      the implementation of logic functions in gene regulation. We investigate the
      interplay between RNA-binding partners in the context of the statistical physics
      of RNA secondary structure and define a linear correlation function between the
      two partners as a measurement of the interdependency of their binding events. We
      demonstrate the emergence of a long-range power-law behavior of this linear
      correlation function. This suggests RNA secondary structure driven
      interdependency between binding sites as a general mechanism for combinatorial
      post-transcriptional gene regulation. 

PMID- 24329297
TI  - Concentration-dependent like-charge pairing of guanidinium ions and effect of
      guanidinium chloride on the structure and dynamics of water from all-atom
      molecular dynamics simulation.
AB  - An all-atom molecular dynamics simulation shows concentration-dependent like
      charge ion pairing of the guanidinium ion in an aqueous solution of guanidinium
      chloride. We have observed two types of like-charge ion pairing for guanidinium
      ions, namely, stacked ion pairs and solvent-separated ion pairs. Interestingly,
      both of these like-charge ion-pair formations are dependent on the concentration
      of guanidinium chloride in water. The probability of stacked like-charge ion-pair
      formation decreases, whereas, the probability of solvent-separated like-charge
      pairing increases as the concentration of guanidinium chloride increases, which
      is shown from radial distribution functions and is confirmed from the energy
      calculations. Besides like-charge ion-pair formation, we also investigated
      guanidinium chloride induced changes in water structure. Hydrogen-bond analysis
      indicates that guanidinium chloride does not alter the strict-hydrogen-bonding
      patterns of water, whereas, it breaks the bend-hydrogen bond and the non-hydrogen
      bonding patterns. Tetrahedral order, nearest neighbor orientation, and distance
      distribution of water molecules around a probe water molecule show the extent of
      water structure distortion. 

PMID- 24329298
TI  - Global dynamics of a stochastic neuronal oscillator.
AB  - Nonlinear oscillators have been used to model neurons that fire periodically in
      the absence of input. These oscillators, which are called neuronal oscillators,
      share some common response structures with other biological oscillations such as
      cardiac cells. In this study, we analyze the dependence of the global dynamics of
      an impulse-driven stochastic neuronal oscillator on the relaxation rate to the
      limit cycle, the strength of the intrinsic noise, and the impulsive input
      parameters. To do this, we use a Markov operator that both reflects the density
      evolution of the oscillator and is an extension of the phase transition curve,
      which describes the phase shift due to a single isolated impulse. Previously, we
      derived the Markov operator for the finite relaxation rate that describes the
      dynamics of the entire phase plane. Here, we construct a Markov operator for the
      infinite relaxation rate that describes the stochastic dynamics restricted to the
      limit cycle. In both cases, the response of the stochastic neuronal oscillator to
      time-varying impulses is described by a product of Markov operators. Furthermore,
      we calculate the number of spikes between two consecutive impulses to relate the
      dynamics of the oscillator to the number of spikes per unit time and the
      interspike interval density. Specifically, we analyze the dynamics of the number
      of spikes per unit time based on the properties of the Markov operators. Each
      Markov operator can be decomposed into stationary and transient components based
      on the properties of the eigenvalues and eigenfunctions. This allows us to
      evaluate the difference in the number of spikes per unit time between the
      stationary and transient responses of the oscillator, which we show to be based
      on the dependence of the oscillator on past activity. Our analysis shows how the
      duration of the past neuronal activity depends on the relaxation rate, the noise
      strength, and the impulsive input parameters. 

PMID- 24329299
TI  - Reluctance of a neutral nanoparticle to enter a charged pore.
AB  - We consider the translocation of a neutral (uncharged) nanoparticle through a
      pore in a thin membrane with constant surface charge density. If the concomitant
      Debye screening layer is sufficiently thin, the resulting forces experienced by
      the particle on its way through the pore are negligible. But when the Debye
      length becomes comparable to the pore diameter, the particle encounters a quite
      significant potential barrier while approaching and entering the pore, and
      symmetrically upon exiting the pore. The main reason is an increasing pressure,
      which acts on the particle when it intrudes into the counter ion cloud of the
      Debye screening layer. In case the polarizability of the particle is different
      (usually smaller) than that of the ambient fluid, a second, much smaller
      contribution to the potential barrier is due to self-energy effects. Our
      numerical treatment of the problem is complemented by analytical approximations
      for sufficiently long cylindrical particles and pores, which agree very well with
      the numerics. 

PMID- 24329300
TI  - Indentation quantification for in-liquid nanomechanical measurement of soft
      material using an atomic force microscope: rate-dependent elastic modulus of live
      cells.
AB  - In this paper, a control-based approach to replace the conventional method to
      achieve accurate indentation quantification is proposed for nanomechanical
      measurement of live cells using atomic force microscope. Accurate indentation
      quantification is central to probe-based nanomechanical property measurement. The
      conventional method for in-liquid nanomechanical measurement of live cells,
      however, fails to accurately quantify the indentation as effects of the relative
      probe acceleration and the hydrodynamic force are not addressed. As a result,
      significant errors and uncertainties are induced in the nanomechanical properties
      measured. In this paper, a control-based approach is proposed to account for
      these adverse effects by tracking the same excitation force profile on both a
      live cell and a hard reference sample through the use of an advanced control
      technique, and by quantifying the indentation from the difference of the
      cantilever base displacement in these two measurements. The proposed control
      based approach not only eliminates the relative probe acceleration effect with no
      need to calibrate the parameters involved, but it also reduces the hydrodynamic
      force effect significantly when the force load rate becomes high. We further
      hypothesize that, by using the proposed control-based approach, the rate
      dependent elastic modulus of live human epithelial cells under different stress
      conditions can be reliably quantified to predict the elasticity evolution of cell
      membranes, and hence can be used to predict cellular behaviors. By implementing
      the proposed approach, the elastic modulus of HeLa cells before and after the
      stress process were quantified as the force load rate was changed over three
      orders of magnitude from 0.1 to 100 Hz, where the amplitude of the applied force
      and the indentation were at 0.4-2 nN and 250-450 nm, respectively. The measured
      elastic modulus of HeLa cells showed a clear power-law dependence on the load
      rate, both before and after the stress process. Moreover, the elastic modulus of
      HeLa cells was substantially reduced by two to five times due to the stress
      process. Thus, our measurements demonstrate that the control-based protocol is
      effective in quantifying and characterizing the evolution of nanomechanical
      properties during the stress process of live cells. 

PMID- 24329301
TI  - Energetics of discrete selectivity bands and mutation-induced transitions in the
      calcium-sodium ion channels family.
AB  - We use Brownian dynamics (BD) simulations to study the ionic conduction and
      valence selectivity of a generic electrostatic model of a biological ion channel
      as functions of the fixed charge Q(f) at its selectivity filter. We are thus able
      to reconcile the discrete calcium conduction bands recently revealed in our BD
      simulations, M0 (Q(f)=1e), M1 (3e), M2 (5e), with a set of sodium conduction
      bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction
      and selectivity bands vs Q(f) for the sodium-calcium channels family. An increase
      of Q(f) leads to an increase of calcium selectivity: L0 (sodium-selective,
      nonblocking channel) -> M0 (nonselective channel) -> L1 (sodium-selective channel
      with divalent block) -> M1 (calcium-selective channel exhibiting the anomalous
      mole fraction effect). We create a consistent identification scheme where the L0
      band is putatively identified with the eukaryotic sodium channel The scheme
      created is able to account for the experimentally observed mutation-induced
      transformations between nonselective channels, sodium-selective channels, and
      calcium-selective channels, which we interpret as transitions between different
      rows of the identification table. By considering the potential energy changes
      during permeation, we show explicitly that the multi-ion conduction bands of
      calcium and sodium channels arise as the result of resonant barrierless
      conduction. The pattern of periodic conduction bands is explained on the basis of
      sequential neutralization taking account of self-energy, as Q(f)(z,i)=ze(1/2+i),
      where i is the order of the band and z is the valence of the ion. Our results
      confirm the crucial influence of electrostatic interactions on conduction and on
      the Ca(2+)/Na(+) valence selectivity of calcium and sodium ion channels. The
      model and results could be also applicable to biomimetic nanopores with charged
      walls.

PMID- 24329302
TI  - Incorporating spatial correlations into multispecies mean-field models.
AB  - In biology, we frequently observe different species existing within the same
      environment. For example, there are many cell types in a tumour, or different
      animal species may occupy a given habitat. In modeling interactions between such
      species, we often make use of the mean-field approximation, whereby spatial
      correlations between the locations of individuals are neglected. Whilst this
      approximation holds in certain situations, this is not always the case, and care
      must be taken to ensure the mean-field approximation is only used in appropriate
      settings. In circumstances where the mean-field approximation is unsuitable, we
      need to include information on the spatial distributions of individuals, which is
      not a simple task. In this paper, we provide a method that overcomes many of the
      failures of the mean-field approximation for an on-lattice volume-excluding birth
      death-movement process with multiple species. We explicitly take into account
      spatial information on the distribution of individuals by including partial
      differential equation descriptions of lattice site occupancy correlations. We
      demonstrate how to derive these equations for the multispecies case and show
      results specific to a two-species problem. We compare averaged discrete results
      to both the mean-field approximation and our improved method, which incorporates
      spatial correlations. We note that the mean-field approximation fails
      dramatically in some cases, predicting very different behavior from that seen
      upon averaging multiple realizations of the discrete system. In contrast, our
      improved method provides excellent agreement with the averaged discrete behavior
      in all cases, thus providing a more reliable modeling framework. Furthermore, our
      method is tractable as the resulting partial differential equations can be solved
      efficiently using standard numerical techniques. 

PMID- 24329303
TI  - Total positive curvature of circular DNA.
AB  - The properties of double-stranded DNA and other chiral molecules depend on the
      local geometry, i.e., on curvature and torsion, yet the paths of closed chain
      molecules are globally restricted by topology. When both of these characteristics
      are to be incorporated in the description of circular chain molecules, e.g.,
      plasmids, it is shown to have implications for the total positive curvature
      integral. For small circular micro-DNAs it follows as a consequence of Fenchel's
      inequality that there must exist a minimum length for the circular plasmids to be
      double stranded. It also follows that all circular micro-DNAs longer than the
      minimum length must be concave, a result that is consistent with typical atomic
      force microscopy images of plasmids. Predictions for the total positive curvature
      of circular micro-DNAs are given as a function of length, and comparisons with
      circular DNAs from the literature are presented. 

PMID- 24329304
TI  - Real-time tracking of neuronal network structure using data assimilation.
AB  - A nonlinear data assimilation technique is applied to determine and track
      effective connections between ensembles of cultured spinal cord neurons measured
      with multielectrode arrays. The method is statistical, depending only on
      confidence intervals, and requiring no form of arbitrary thresholding. In
      addition, the method updates connection strengths sequentially, enabling real
      time tracking of nonstationary networks. The ensemble Kalman filter is used with
      a generic spiking neuron model to estimate connection strengths as well as other
      system parameters to deal with model mismatch. The method is validated on noisy
      synthetic data from Hodgkin-Huxley model neurons before being used to find
      network connections in the neural culture recordings. 

PMID- 24329305
TI  - Using dominant eigenvalue analysis to predict formation of alternans in the
      heart.
AB  - Ventricular fibrillation at the whole heart level is often preceded by the
      alternation of action potential duration (APD), i.e., alternans, at the cellular
      level. As proven in many experiments, traditional approaches based on the slope
      of the restitution curve have not been successful in predicting alternans
      formation. Recently, a technique has been theoretically developed based on
      dominant eigenvalue analysis to predict alternans formation in isolated cardiac
      myocytes. Here, we aimed to demonstrate that this technique can be applied to
      predict alternans formation at the whole heart level. Optical mapping was
      performed in Langendorff-perfused hearts from New Zealand white rabbits (n = 4),
      which were paced at decreasing basic cycle lengths to introduce APD alternans. In
      each heart, the basic cycle length corresponding to the local onset of alternans,
      B(onset), was determined and two regions of the heart were identified at
      B(onset): one region which exhibited alternans (1:1(alt)) and one which did not
      (1:1). Corresponding two-dimensional eigenvalue (lambda) maps were generated
      using principal component analysis by analyzing action potentials after short
      perturbations from the steady state, and mean eigenvalues (lambda[over -]) were
      calculated separately for the 1:1 and 1:1(alt) regions. We demonstrated that
      lambda[over -] calculated at B(onset) was significantly different (p<0.05)
      between the two regions. Our results suggest that this dominant eigenvalue
      technique can be used to successfully predict the local alternans formation in
      the heart.

PMID- 24329306
TI  - Evolutionary advantage via common action of recombination and neutrality.
AB  - We investigate evolution models with recombination and neutrality. We consider
      the Crow-Kimura (parallel) mutation-selection model with the neutral fitness
      landscape, in which there is a central peak with high fitness A, and some of 1
      point mutants have the same high fitness A, while the fitness of other sequences
      is 0. We find that the effect of recombination and neutrality depends on the
      concrete version of both neutrality and recombination. We consider three versions
      of neutrality: (a) all the nearest neighbor sequences of the peak sequence have
      the same high fitness A; (b) all the l-point mutations in a piece of genome of
      length l>=1 are neutral; (c) the neutral sequences are randomly distributed among
      the nearest neighbors of the peak sequences. We also consider three versions of
      recombination: (I) the simple horizontal gene transfer (HGT) of one nucleotide;
      (II) the exchange of a piece of genome of length l, HGT-l; (III) two-point
      crossover recombination (2CR). For the case of (a), the 2CR gives a rather strong
      contribution to the mean fitness, much stronger than that of HGT for a large
      genome length L. For the random distribution of neutral sequences there is a
      critical degree of neutrality nu(c), and for MU<MU(c) and (MU(c)-MU) is not
      large, the 2CR suppresses the mean fitness while HGT increases it; for nu much
      larger than nu(c), the 2CR and HGT-l increase the mean fitness larger than that
      of the HGT. We also consider the recombination in the case of smooth fitness
      landscapes. The recombination gives some advantage in the evolutionary dynamics,
      where recombination distinguishes clearly the mean-field-like evolutionary
      factors from the fluctuation-like ones. By contrast, mutations affect the mean
      field-like and fluctuation-like factors similarly. Consequently, recombination
      can accelerate the non-mean-field (fluctuation) type dynamics without
      considerably affecting the mean-field-like factors.

PMID- 24329307
TI  - Equilibrium electrodeformation of a spheroidal vesicle in an ac electric field.
AB  - In this work, we develop a theoretical model to explain the equilibrium
      spheroidal deformation of a giant unilamellar vesicle (GUV) under an alternating
      (ac) electric field. Suspended in a leaky dielectric fluid, the vesicle membrane
      is modeled as a thin capacitive spheroidal shell. The equilibrium vesicle shape
      results from the balance between mechanical forces from the viscous fluid, the
      restoring elastic membrane forces, and the externally imposed electric forces.
      Our spheroidal model predicts a deformation-dependent transmembrane potential,
      and is able to capture large deformation of a vesicle under an electric field. A
      detailed comparison against both experiments and small-deformation
      (quasispherical) theory showed that the spheroidal model gives better agreement
      with experiments in terms of the dependence on fluid conductivity ratio,
      permittivity ratio, vesicle size, electric field strength, and frequency. The
      spheroidal model also allows for an asymptotic analysis on the crossover
      frequency where the equilibrium vesicle shape crosses over between prolate and
      oblate shapes. Comparisons show that the spheroidal model gives better agreement
      with experimental observations. 

PMID- 24329308
TI  - Spread of infectious diseases in a hyperbolic reaction-diffusion susceptible
      infected-removed model.
AB  - A one-dimensional hyperbolic reaction-diffusion model of epidemics is developed
      to describe the dynamics of diseases spread occurring in an environment where
      three kinds of individuals mutually interact: the susceptibles, the infectives,
      and the removed. It is assumed that the disease is transmitted from the infected
      population to the susceptible one according to a nonlinear convex incidence rate.
      The model, based upon the framework of extended thermodynamics, removes the
      unphysical feature of instantaneous diffusive effects, which is typical of
      parabolic models. Linear stability analyses are performed to study the nature of
      the equilibrium states against uniform and nonuniform perturbations. Emphasis is
      given to the occurrence of Hopf and Turing bifurcations, which break the temporal
      and the spatial symmetry of the system, respectively. The existence of traveling
      wave solutions connecting two steady states is also discussed. The governing
      equations are also integrated numerically to validate the analytical results and
      to characterize the spatiotemporal evolution of diseases. 

PMID- 24329309
TI  - Adaptive grid generation in a patient-specific cerebral aneurysm.
AB  - Adapting grid density to flow behavior provides the advantage of increasing
      solution accuracy while decreasing the number of grid elements in the simulation
      domain, therefore reducing the computational time. One method for grid adaptation
      requires successive refinement of grid density based on observed solution
      behavior until the numerical errors between successive grids are negligible.
      However, such an approach is time consuming and it is often neglected by the
      researchers. We present a technique to calculate the grid size distribution of an
      adaptive grid for computational fluid dynamics (CFD) simulations in a complex
      cerebral aneurysm geometry based on the kinematic curvature and torsion
      calculated from the velocity field. The relationship between the kinematic
      characteristics of the flow and the element size of the adaptive grid leads to a
      mathematical equation to calculate the grid size in different regions of the
      flow. The adaptive grid density is obtained such that it captures the more
      complex details of the flow with locally smaller grid size, while less complex
      flow characteristics are calculated on locally larger grid size. The current
      study shows that kinematic curvature and torsion calculated from the velocity
      field in a cerebral aneurysm can be used to find the locations of complex flow
      where the computational grid needs to be refined in order to obtain an accurate
      solution. We found that the complexity of the flow can be adequately described by
      velocity and vorticity and the angle between the two vectors. For example, inside
      the aneurysm bleb, at the bifurcation, and at the major arterial turns the
      element size in the lumen needs to be less than 10% of the artery radius, while
      at the boundary layer, the element size should be smaller than 1% of the artery
      radius, for accurate results within a 0.5% relative approximation error. This
      technique of quantifying flow complexity and adaptive remeshing has the potential
      to improve results accuracy and reduce computational time for patient-specific
      hemodynamics simulations, which are used to help assess the likelihood of
      aneurysm rupture using CFD calculated flow patterns. 

PMID- 24329310
TI  - Parallel logic gates in synthetic gene networks induced by non-Gaussian noise.
AB  - The recent idea of logical stochastic resonance is verified in synthetic gene
      networks induced by non-Gaussian noise. We realize the switching between two
      kinds of logic gates under optimal moderate noise intensity by varying two
      different tunable parameters in a single gene network. Furthermore, in order to
      obtain more logic operations, thus providing additional information processing
      capacity, we obtain in a two-dimensional toggle switch model two complementary
      logic gates and realize the transformation between two logic gates via the
      methods of changing different parameters. These simulated results contribute to
      improve the computational power and functionality of the networks. 

PMID- 24329311
TI  - Channel-noise-induced stochastic facilitation in an auditory brainstem neuron
      model.
AB  - Neuronal membrane potentials fluctuate stochastically due to conductance changes
      caused by random transitions between the open and closed states of ion channels.
      Although it has previously been shown that channel noise can nontrivially affect
      neuronal dynamics, it is unknown whether ion-channel noise is strong enough to
      act as a noise source for hypothesized noise-enhanced information processing in
      real neuronal systems, i.e., "stochastic facilitation". Here we demonstrate that
      biophysical models of channel noise can give rise to two kinds of recently
      discovered stochastic facilitation effects in a Hodgkin-Huxley-like model of
      auditory brainstem neurons. The first, known as slope-based stochastic resonance
      (SBSR), enables phasic neurons to emit action potentials that can encode the
      slope of inputs that vary slowly relative to key time constants in the model. The
      second, known as inverse stochastic resonance (ISR), occurs in tonically firing
      neurons when small levels of noise inhibit tonic firing and replace it with
      burstlike dynamics. Consistent with previous work, we conclude that channel noise
      can provide significant variability in firing dynamics, even for large numbers of
      channels. Moreover, our results show that possible associated computational
      benefits may occur due to channel noise in neurons of the auditory brainstem.
      This holds whether the firing dynamics in the model are phasic (SBSR can occur
      due to channel noise) or tonic (ISR can occur due to channel noise). 

PMID- 24329312
TI  - Epidemic thresholds for bipartite networks.
AB  - It is well known that sexually transmitted diseases (STD) spread across a network
      of human sexual contacts. This network is most often bipartite, as most STD are
      transmitted between men and women. Even though network models in epidemiology
      have quite a long history now, there are few general results about bipartite
      networks. One of them is the simple dependence, predicted using the mean field
      approximation, between the epidemic threshold and the average and variance of the
      degree distribution of the network. Here we show that going beyond this
      approximation can lead to qualitatively different results that are supported by
      numerical simulations. One of the new features, that can be relevant for
      applications, is the existence of a critical value for the infectivity of each
      population, below which no epidemics can arise, regardless of the value of the
      infectivity of the other population. 

PMID- 24329313
TI  - Normalized modularity optimization method for community identification with
      degree adjustment.
AB  - As a fundamental problem in network study, community identification has attracted
      much attention from different fields. Representing a seminal work in this area,
      the modularity optimization method has been widely applied and studied. However,
      this method has issues in resolution limit and extreme degeneracy and may not
      perform well for networks with unbalanced structures. Although several methods
      have been proposed to overcome these limitations, they are all based on the
      original idea of defining modularity through comparing the total number of edges
      within the putative communities in the observed network with that in an
      equivalent randomly generated network. In this paper, we show that this
      modularity definition is not suitable to analyze some networks such as those with
      unbalanced structures. Instead, we propose to define modularity through the
      average degree within the communities and formulate modularity as comparing the
      sum of average degree within communities of the observed network to that of an
      equivalent randomly generated network. In addition, we also propose a degree
      adjusted approach for further improvement when there are unbalanced structures.
      We analyze the theoretical properties of our degree adjusted method. Numerical
      experiments for both artificial networks and real networks demonstrate that
      average degree plays an important role in network community identification, and
      our proposed methods have better performance than existing ones. 

PMID- 24329314
TI  - Voter models with contrarian agents.
AB  - In the voter and many other opinion formation models, agents are assumed to
      behave as congregators (also called the conformists); they are attracted to the
      opinions of others. In this study I investigate linear extensions of the voter
      model with contrarian agents. An agent is either congregator or contrarian and
      assumes a binary opinion. I investigate three models that differ in the behavior
      of the contrarian toward other agents. In model 1, contrarians mimic the opinions
      of other contrarians and oppose (i.e., try to select the opinion opposite to)
      those of congregators. In model 2, contrarians mimic the opinions of congregators
      and oppose those of other contrarians. In model 3, contrarians oppose anybody. In
      all models, congregators are assumed to like anybody. I show that even a small
      number of contrarians prohibits the consensus in the entire population to be
      reached in all three models. I also obtain the equilibrium distributions using
      the van Kampen small-fluctuation approximation and the Fokker-Planck equation for
      the case of many contrarians and a single contrarian, respectively. I show that
      the fluctuation around the symmetric coexistence equilibrium is much larger in
      model 2 than in models 1 and 3 when contrarians are rare. 

PMID- 24329315
TI  - Asymptotically inspired moment-closure approximation for adaptive networks.
AB  - Adaptive social networks, in which nodes and network structure coevolve, are
      often described using a mean-field system of equations for the density of node
      and link types. These equations constitute an open system due to dependence on
      higher-order topological structures. We propose a new approach to moment closure
      based on the analytical description of the system in an asymptotic regime. We
      apply the proposed approach to two examples of adaptive networks: recruitment to
      a cause model and adaptive epidemic model. We show a good agreement between the
      improved mean-field prediction and simulations of the full network system. 

PMID- 24329316
TI  - Percolation of interdependent networks with intersimilarity.
AB  - Real data show that interdependent networks usually involve intersimilarity.
      Intersimilarity means that a pair of interdependent nodes have neighbors in both
      networks that are also interdependent [Parshani et al. Europhys. Lett. 92, 68002
      (2010)]. For example, the coupled worldwide port network and the global airport
      network are intersimilar since many pairs of linked nodes (neighboring cities),
      by direct flights and direct shipping lines, exist in both networks. Nodes in
      both networks in the same city are regarded as interdependent. If two neighboring
      nodes in one network depend on neighboring nodes in the other network, we call
      these links common links. The fraction of common links in the system is a measure
      of intersimilarity. Previous simulation results of Parshani et al. suggest that
      intersimilarity has considerable effects on reducing the cascading failures;
      however, a theoretical understanding of this effect on the cascading process is
      currently missing. Here we map the cascading process with intersimilarity to a
      percolation of networks composed of components of common links and noncommon
      links. This transforms the percolation of intersimilar system to a regular
      percolation on a series of subnetworks, which can be solved analytically. We
      apply our analysis to the case where the network of common links is an Erdos
      Renyi (ER) network with the average degree K, and the two networks of noncommon
      links are also ER networks. We show for a fully coupled pair of ER networks, that
      for any K>=0, although the cascade is reduced with increasing K, the phase
      transition is still discontinuous. Our analysis can be generalized to any kind of
      interdependent random network systems.

PMID- 24329317
TI  - Phase ordering in coupled noisy bistable systems on scale-free networks.
AB  - We study a system consisting of diffusively coupled noisy bistable elements on a
      scale-free random network. This system exhibits an order-disorder phase
      transition as the noise intensity is varied. The phase ordering process takes
      place consecutively and in order of the degrees, reflecting strong degree
      heterogeneity of the scale-free network. A nonlinear Fokker-Planck equation
      describing the network dynamics is derived under mean-field approximation of the
      network, and is used to explain the phase ordering dynamics of the system. 

PMID- 24329318
TI  - Disentangling different types of El Nino episodes by evolving climate network
      analysis.
AB  - Complex network theory provides a powerful toolbox for studying the structure of
      statistical interrelationships between multiple time series in various scientific
      disciplines. In this work, we apply the recently proposed climate network
      approach for characterizing the evolving correlation structure of the Earth's
      climate system based on reanalysis data for surface air temperatures. We provide
      a detailed study of the temporal variability of several global climate network
      characteristics. Based on a simple conceptual view of red climate networks (i.e.,
      networks with a comparably low number of edges), we give a thorough
      interpretation of our evolving climate network characteristics, which allows a
      functional discrimination between recently recognized different types of El Nino
      episodes. Our analysis provides deep insights into the Earth's climate system,
      particularly its global response to strong volcanic eruptions and large-scale
      impacts of different phases of the El Nino Southern Oscillation. 

PMID- 24329320
TI  - Analytical solution of a stochastic model of risk spreading with global coupling.
AB  - We study a stochastic matrix model to understand the mechanics of risk spreading
      (or bet hedging) by dispersion. Up to now, this model has been mostly dealt with
      numerically, except for the well-mixed case. Here, we present an analytical
      result that shows that optimal dispersion leads to Zipf's law. Moreover, we found
      that the arithmetic ensemble average of the total growth rate converges to the
      geometric one, because the sample size is finite. 

PMID- 24329319
TI  - Robustness of cooperation on scale-free networks under continuous topological
      change.
AB  - In this paper, we numerically investigate the robustness of cooperation clusters
      in prisoner's dilemma played on scale-free networks, where the network topologies
      change by continuous removal and addition of nodes. Each removal and addition can
      be either random or intentional. We therefore have four different strategies in
      changing network topology: random removal and random addition (RR), random
      removal and preferential addition (RP), targeted removal and random addition
      (TR), and targeted removal and preferential addition (TP). We find that
      cooperation clusters are most fragile against TR, while they are most robust
      against RP, even for large values of the temptation coefficient for defection.
      The effect of the degree mixing pattern of the network is not the primary factor
      for the robustness of cooperation under continuous change in network topology,
      which is quite different from the cases observed in static networks. Cooperation
      clusters become more robust as the number of links of hubs occupied by
      cooperators increase. Our results might infer the fact that a huge variety of
      individuals is needed for maintaining global cooperation in social networks in
      the real world where each node representing an individual is constantly removed
      and added. 

PMID- 24329321
TI  - Network reliability: the effect of local network structure on diffusive
      processes.
AB  - This paper reintroduces the network reliability polynomial, introduced by Moore
      and Shannon [Moore and Shannon, J. Franklin Inst. 262, 191 (1956)], for studying
      the effect of network structure on the spread of diseases. We exhibit a
      representation of the polynomial that is well suited for estimation by
      distributed simulation. We describe a collection of graphs derived from Erdos
      Renyi and scale-free-like random graphs in which we have manipulated
      assortativity-by-degree and the number of triangles. We evaluate the network
      reliability for all of these graphs under a reliability rule that is related to
      the expected size of a connected component. Through these extensive simulations,
      we show that for positively or neutrally assortative graphs, swapping edges to
      increase the number of triangles does not increase the network reliability. Also,
      positively assortative graphs are more reliable than neutral or disassortative
      graphs with the same number of edges. Moreover, we show the combined effect of
      both assortativity-by-degree and the presence of triangles on the critical point
      and the size of the smallest subgraph that is reliable. 

PMID- 24329322
TI  - Percolation in multiplex networks with overlap.
AB  - From transportation networks to complex infrastructures, and to social and
      communication networks, a large variety of systems can be described in terms of
      multiplexes formed by a set of nodes interacting through different networks
      (layers). Multiplexes may display an increased fragility with respect to the
      single layers that constitute them. However, so far the overlap of the links in
      different layers has been mostly neglected, despite the fact that it is an
      ubiquitous phenomenon in most multiplexes. Here, we show that the overlap among
      layers can improve the robustness of interdependent multiplex systems and change
      the critical behavior of the percolation phase transition in a complex way. 

PMID- 24329323
TI  - Bootstrapping under constraint for the assessment of group behavior in human
      contact networks.
AB  - The increasing availability of time- and space-resolved data describing human
      activities and interactions gives insights into both static and dynamic
      properties of human behavior. In practice, nevertheless, real-world data sets can
      often be considered as only one realization of a particular event. This
      highlights a key issue in social network analysis: the statistical significance
      of estimated properties. In this context, we focus here on the assessment of
      quantitative features of specific subset of nodes in empirical networks. We
      present a method of statistical resampling based on bootstrapping groups of nodes
      under constraints within the empirical network. The method enables us to define
      acceptance intervals for various null hypotheses concerning relevant properties
      of the subset of nodes under consideration in order to characterize by a
      statistical test its behavior as "normal" or not. We apply this method to a high
      resolution data set describing the face-to-face proximity of individuals during
      two colocated scientific conferences. As a case study, we show how to probe
      whether colocating the two conferences succeeded in bringing together the two
      corresponding groups of scientists. 

PMID- 24329324
TI  - Analytical investigation of the faster-is-slower effect with a simplified
      phenomenological model.
AB  - We investigate the mechanism of the phenomenon called the "faster-is
      slower"effect in pedestrian flow studies analytically with a simplified
      phenomenological model. It is well known that the flow rate is maximized at a
      certain strength of the driving force in simulations using the social force model
      when we consider the discharge of self-driven particles through a bottleneck. In
      this study, we propose a phenomenological and analytical model based on a
      mechanics-based modeling to reveal the mechanism of the phenomenon. We show that
      our reduced system, with only a few degrees of freedom, still has similar
      properties to the original many-particle system and that the effect comes from
      the competition between the driving force and the nonlinear friction from the
      model. Moreover, we predict the parameter dependences on the effect from our
      model qualitatively, and they are confirmed numerically by using the social force
      model. 

PMID- 24329325
TI  - Mobility of solitons in one-dimensional lattices with the cubic-quintic
      nonlinearity.
AB  - We investigate mobility regimes for localized modes in the discrete nonlinear
      Schrodinger (DNLS) equation with the cubic-quintic on-site terms. Using the
      variational approximation, the largest soliton's total power admitting
      progressive motion of kicked discrete solitons is predicted by comparing the
      effective kinetic energy with the respective Peierls-Nabarro (PN) potential
      barrier. The prediction, for the DNLS model with the cubic-only nonlinearity too,
      demonstrates a reasonable agreement with numerical findings. A small self
      focusing quintic term quickly suppresses the mobility. In the case of the
      competition between the cubic self-focusing and quintic self-defocusing terms, we
      identify parameter regions where odd and even fundamental modes exchange their
      stability, involving intermediate asymmetric modes. In this case, stable solitons
      can be set in motion by kicking, so as to let them pass the PN barrier. Unstable
      solitons spontaneously start oscillatory or progressive motion, if they are
      located, respectively, below or above a mobility threshold. Collisions between
      moving discrete solitons, at the competing nonlinearities frame, are studied too.

PMID- 24329326
TI  - Extremal spacings between eigenphases of random unitary matrices and their tensor
      products.
AB  - Extremal spacings between eigenphases of random unitary matrices of size N
      pertaining to circular ensembles are investigated. Explicit probability
      distributions for the minimal spacing for various ensembles are derived for N=4.
      We study ensembles of tensor product of k random unitary matrices of size n which
      describe independent evolution of a composite quantum system consisting of k
      subsystems. In the asymptotic case, as the total dimension N=n(k) becomes large,
      the nearest neighbor distribution P(s) becomes Poissonian, but statistics of
      extreme spacings P(s(min)) and P(s(max)) reveal certain deviations from the
      Poissonian behavior.

PMID- 24329327
TI  - Passive band-gap reconfiguration born from bifurcation asymmetry.
AB  - Current periodic structures are constrained to have fixed energy transmission
      behavior unless active control or component replacement is used to alter their
      wave propagation characteristics. The introduction of nonlinearity to generate
      multiple stable equilibria is an alternative strategy for realizing distinct
      energy propagation behaviors. We investigate the creation of a reconfigurable
      band-gap system by implementing passive switching between multiple stable states
      of equilibrium, to alter the level of energy attenuation in response to
      environmental stimuli. The ability to avoid potentially catastrophic loads is
      demonstrated by tailoring the bandpass and band-gap regions to coalesce for two
      stable equilibria and varying an external load parameter to trigger a
      bifurcation. The proposed phenomenon could be utilized in remote or autonomous
      applications where component modifications and active control are impractical. 

PMID- 24329328
TI  - Characterizing the deterministic nature of individual power dropouts in
      semiconductor lasers subject to delayed feedback.
AB  - We implement a method to identify the deterministic nature of specific events in
      the dynamics of a semiconductor laser subject to time-delayed optical feedback.
      Specifically, we study the power dropouts in the low-frequency fluctuations
      regime on an individual event basis and identify whether the underlying dominant
      mechanism is deterministic. Our approach is based on sychronization with a twin
      system in a symmetric relay configuration. We investigate the dependence of the
      fraction of deterministically driven (i.e., synchronized) dropouts on the laser's
      pump current as a key parameter. Our experimental results are corroborated by
      numerical modeling based on rate equations. Our numerical findings also provide
      insights into the influence of spontaneous emission noise. 

PMID- 24329329
TI  - Chaotic dynamics of a microswimmer in Poiseuille flow.
AB  - The chaotic dynamics of pointlike, spherical particles in cylindrical Poiseuille
      flow is theoretically characterized and numerically confirmed when their own
      intrinsic swimming velocity undergoes temporal fluctuations around an average
      value. Two dimensionless ratios associated with the three significant temporal
      scales of the problem are identified that fully determine the chaos scenario. In
      particular, small but finite periodic fluctuations of swimming speed result in
      chaotic or regular motion depending on the position and orientation of the
      microswimmer with respect to the flow center line. Remarkably, the spatial
      extension of chaotic microswimmers is found to depend crucially on the
      fluctuations' period and amplitude and to be highly sensitive to the Fourier
      spectrum of the fluctuations. This has implications for the design of artificial
      microswimmers. 

PMID- 24329330
TI  - Solitons and thermal fluctuations in strongly nonlinear solids.
AB  - We study a chain of anharmonic springs with tunable power law interactions as a
      minimal model to explore the propagation of strongly nonlinear solitary wave
      excitations in a background of thermal fluctuations. By treating the solitary
      waves as quasiparticles, we derive an effective Langevin equation and obtain
      their damping rate and thermal diffusion. These analytical findings compare
      favorably against numerical results from a Langevin dynamic simulation. In our
      chains composed of two-sided nonlinear springs, we report the existence of an
      expansion solitary wave (antisoliton) in addition to the compressive solitary
      waves observed for noncohesive macroscopic particles. 

PMID- 24329331
TI  - Onset of dynamic activity in globally coupled excitable and oscillatory units.
AB  - The onset of dynamic activity is studied in heterogeneous populations of globally
      coupled units such that each unit is either excitable or oscillatory depending on
      its parameter. By varying the mean of the parameter distribution as well as
      coupling strength, we show that all or part of the populations studied have
      common features: similar phase diagrams, hysteresis near or at the onset of
      dynamic activity, and a fractional power law obeyed by an order parameter. A
      simplified model is proposed to explain these results. 

PMID- 24329332
TI  - Generalized synchronization in relay systems with instantaneous coupling.
AB  - We demonstrate the existence of generalized synchronization in systems that act
      as mediators between two dynamical units that, in turn, show complete
      synchronization with each other. These are the so-called relay systems.
      Specifically, we analyze the Lyapunov spectrum of the full system to elucidate
      when complete and generalized synchronization appear. We show that once a
      critical coupling strength is achieved, complete synchronization emerges between
      the systems to be synchronized, and at the same point, generalized
      synchronization with the relay system also arises. Next, we use two nonlinear
      measures based on the distance between phase-space neighbors to quantify the
      generalized synchronization in discretized time series. Finally, we
      experimentally show the robustness of the phenomenon and of the theoretical tools
      here proposed to characterize it. 

PMID- 24329333
TI  - Infinite-dimensional Bayesian filtering for detection of quasiperiodic phenomena
      in spatiotemporal data.
AB  - This paper introduces a spatiotemporal resonator model and an inference method
      for detection and estimation of nearly periodic temporal phenomena in
      spatiotemporal data. The model is derived as a spatial extension of a stochastic
      harmonic resonator model, which can be formulated in terms of a stochastic
      differential equation. The spatial structure is included by introducing linear
      operators, which affect both the oscillations and damping, and by choosing the
      appropriate spatial covariance structure of the driving time-white noise process.
      With the choice of the linear operators as partial differential operators, the
      resonator model becomes a stochastic partial differential equation, which is
      compatible with infinite-dimensional Kalman filtering. The resulting infinite
      dimensional Kalman filtering problem allows for a computationally efficient
      solution as the computational cost scales linearly with measurements in the
      temporal dimension. This framework is applied to weather prediction and to
      physiological noise elimination in functional magnetic resonance imaging brain
      data. 

PMID- 24329334
TI  - Edge of chaos and genesis of turbulence.
AB  - The edge of chaos is analyzed in a spatially extended system, modeled by the
      regularized long-wave equation, prior to the transition to permanent
      spatiotemporal chaos. In the presence of coexisting attractors, a chaotic saddle
      is born at the basin boundary due to a smooth-fractal metamorphosis. As a control
      parameter is varied, the chaotic transient evolves to well-developed transient
      turbulence via a cascade of fractal-fractal metamorphoses. The edge state
      responsible for the edge of chaos and the genesis of turbulence is an unstable
      traveling wave in the laboratory frame, corresponding to a saddle point lying at
      the basin boundary in the Fourier space. 

PMID- 24329335
TI  - Extreme events in excitable systems and mechanisms of their generation.
AB  - We study deterministic systems, composed of excitable units of FitzHugh-Nagumo
      type, that are capable of self-generating and self-terminating strong deviations
      from their regular dynamics without the influence of noise or parameter change.
      These deviations are rare, short-lasting, and recurrent and can therefore be
      regarded as extreme events. Employing a range of methods we analyze dynamical
      properties of the systems, identifying features in the systems' dynamics that may
      qualify as precursors to extreme events. We investigate these features and
      elucidate mechanisms that may be responsible for the generation of the extreme
      events. 

PMID- 24329336
TI  - Statistics of quantum transport in weakly nonideal chaotic cavities.
AB  - We consider statistics of electronic transport in chaotic cavities where time
      reversal symmetry is broken and one of the leads is weakly nonideal; that is, it
      contains tunnel barriers characterized by tunneling probabilities Gamma(i). Using
      symmetric function expansions and a generalized Selberg integral, we develop a
      systematic perturbation theory in 1-Gamma(i) valid for an arbitrary number of
      channels and obtain explicit formulas up to second order for the average and
      variance of the conductance and for the average shot noise. Higher moments of the
      conductance are considered to leading order.

PMID- 24329337
TI  - Quantum localization of chaotic eigenstates and the level spacing distribution.
AB  - The phenomenon of quantum localization in classically chaotic eigenstates is one
      of the main issues in quantum chaos (or wave chaos), and thus plays an important
      role in general quantum mechanics or even in general wave mechanics. In this work
      we propose two different localization measures characterizing the degree of
      quantum localization, and study their relation to another fundamental aspect of
      quantum chaos, namely the (energy) spectral statistics. Our approach and method
      is quite general, and we apply it to billiard systems. One of the signatures of
      the localization of chaotic eigenstates is a fractional power-law repulsion
      between the nearest energy levels in the sense that the probability density to
      find successive levels on a distance S goes like [proportionality]S(beta) for
      small S, where 0<=beta<=1, and beta=1 corresponds to completely extended states.
      We show that there is a clear functional relation between the exponent beta and
      the two different localization measures. One is based on the information entropy
      and the other one on the correlation properties of the Husimi functions. We show
      that the two definitions are surprisingly linearly equivalent. The approach is
      applied in the case of a mixed-type billiard system [M. Robnik, J. Phys. A: Math.
      Gen. 16, 3971 (1983)], in which the separation of regular and chaotic eigenstates
      is performed.

PMID- 24329338
TI  - Rational solitons of wave resonant-interaction models.
AB  - Integrable models of resonant interaction of two or more waves in 1+1 dimensions
      are known to be of applicative interest in several areas. Here we consider a
      system of three coupled wave equations which includes as special cases the vector
      nonlinear Schrodinger equations and the equations describing the resonant
      interaction of three waves. The Darboux-Dressing construction of soliton
      solutions is applied under the condition that the solutions have rational, or
      mixed rational-exponential, dependence on coordinates. Our algebraic construction
      relies on the use of nilpotent matrices and their Jordan form. We systematically
      search for all bounded rational (mixed rational-exponential) solutions and find a
      broad family of such solutions of the three wave resonant interaction equations. 

PMID- 24329339
TI  - Particle current on flexible surfaces excited by harmonic waves.
AB  - In this paper, a study on the directed particle current on flexible surfaces
      excited by a harmonic wave is reported. The proposed theory considers three
      different models for the kinematics of the surface, namely the Euler-Bernoulli,
      Timoshenko, and Rayleigh surface wave models. The particle-surface interaction
      terms in the theory incorporate Coulomb friction and inelastic collision between
      the particle and the surface. Three possible phases of motion, namely sticking,
      sliding, and jumping, are considered, and the phase transition boundaries are
      estimated analytically for a general surface model. The effect of various
      parameters on the particle current and certain statistical features of the
      particle motion are then studied numerically. Remarkably, the particle current
      spectra exhibit, in addition to resonance modes, antiresonance and secondary
      resonance modes and transversal zero crossings. These features have interesting
      implications for the particle dynamics in terms of dynamic jamming states and
      particle eddies, which are pointed out. Under certain restricted conditions,
      averaging calculations are also performed and compared with the corresponding
      numerical simulations. 

PMID- 24329340
TI  - Quasiperiodicity route to spatiotemporal chaos in one-dimensional pattern-forming
      systems.
AB  - We propose a route to spatiotemporal chaos for one-dimensional stationary
      patterns, which is a natural extension of the quasiperiodicity route for low
      dimensional chaos to extended systems. This route is studied through a universal
      model of pattern formation. The model exhibits a scenario where stationary
      patterns become spatiotemporally chaotic through two successive bifurcations.
      First, the pattern undergoes a subcritical Andronov-Hopf bifurcation leading to
      an oscillatory pattern. Subsequently, a secondary bifurcation gives rise to an
      oscillation with an incommensurable frequency with respect to the former one.
      This last bifurcation is responsible for the spatiotemporally chaotic behavior.
      The Lyapunov spectrum enables us to identify the complex behavior observed as
      spatiotemporal chaos, and also from the larger Lyapunov exponents characterize
      the above instabilities. 

PMID- 24329341
TI  - Predicting critical transitions in dynamical systems from time series using
      nonstationary probability density modeling.
AB  - A time series analysis method for predicting the probability density of a
      dynamical system is proposed. A nonstationary parametric model of the probability
      density is estimated from data within a maximum likelihood framework and then
      extrapolated to forecast the future probability density and explore the system
      for critical transitions or tipping points. A full systematic account of
      parameter uncertainty is taken. The technique is generic, independent of the
      underlying dynamics of the system. The method is verified on simulated data and
      then applied to prediction of Arctic sea-ice extent. 

PMID- 24329342
TI  - Electric-field-controlled unpinning of scroll waves.
AB  - Three-dimensional excitation vortices exist in systems such as chemical reactions
      and the human heart. Their one-dimensional rotation backbone can pin to
      unexcitable heterogeneities, which greatly affect the structure, dynamics, and
      lifetime of the vortex. In experiments with the Belousov-Zhabotinsky reaction, we
      demonstrate vortex unpinning from a pair of inert and impermeable spheres using
      externally applied electric fields. Unpinning occurs abruptly but is preceded by
      a slow reorientation and deformation of the initially circular vortex loop. Our
      experimental findings are reproduced by numerical simulations of an excitable
      reaction-diffusion-advection model. 

PMID- 24329343
TI  - Exponential quantum spreading in a class of kicked rotor systems near high-order
      resonances.
AB  - Long-lasting exponential quantum spreading was recently found in a simple but
      very rich dynamical model, namely, an on-resonance double-kicked rotor model [J.
      Wang, I. Guarneri, G. Casati, and J. B. Gong, Phys. Rev. Lett. 107, 234104
      (2011)]. The underlying mechanism, unrelated to the chaotic motion in the
      classical limit but resting on quasi-integrable motion in a pseudoclassical
      limit, is identified for one special case. By presenting a detailed study of the
      same model, this work offers a framework to explain long-lasting exponential
      quantum spreading under much more general conditions. In particular, we adopt the
      so-called "spinor" representation to treat the kicked-rotor dynamics under high
      order resonance conditions and then exploit the Born-Oppenheimer approximation to
      understand the dynamical evolution. It is found that the existence of a flat band
      (or an effectively flat band) is one important feature behind why and how the
      exponential dynamics emerges. It is also found that a quantitative prediction of
      the exponential spreading rate based on an interesting and simple pseudoclassical
      map may be inaccurate. In addition to general interests regarding the question of
      how exponential behavior in quantum systems may persist for a long time scale,
      our results should motivate further studies toward a better understanding of high
      order resonance behavior in delta-kicked quantum systems. 

PMID- 24329344
TI  - Kicked-Harper model versus on-resonance double-kicked rotor model: from spectral
      difference to topological equivalence.
AB  - Recent studies have established that, in addition to the well-known kicked-Harper
      model (KHM), an on-resonance double-kicked rotor (ORDKR) model also has
      Hofstadter's butterfly Floquet spectrum, with strong resemblance to the standard
      Hofstadter spectrum that is a paradigm in studies of the integer quantum Hall
      effect. Earlier it was shown that the quasienergy spectra of these two dynamical
      models (i) can exactly overlap with each other if an effective Planck constant
      takes irrational multiples of 2pi and (ii) will be different if the same
      parameter takes rational multiples of 2pi. This work makes detailed comparisons
      between these two models, with an effective Planck constant given by 2piM/N,
      where M and N are coprime and odd integers. It is found that the ORDKR spectrum
      (with two periodic kicking sequences having the same kick strength) has one flat
      band and N-1 nonflat bands with the largest bandwidth decaying in a power law as
      ~K(N+2), where K is a kick strength parameter. The existence of a flat band is
      strictly proven and the power-law scaling, numerically checked for a number of
      cases, is also analytically proven for a three-band case. By contrast, the KHM
      does not have any flat band and its bandwidths scale linearly with K. This is
      shown to result in dramatic differences in dynamical behavior, such as transient
      (but extremely long) dynamical localization in ORDKR, which is absent in the KHM.
      Finally, we show that despite these differences, there exist simple extensions of
      the KHM and ORDKR model (upon introducing an additional periodic phase parameter)
      such that the resulting extended KHM and ORDKR model are actually topologically
      equivalent, i.e., they yield exactly the same Floquet-band Chern numbers and
      display topological phase transitions at the same kick strengths. A theoretical
      derivation of this topological equivalence is provided. These results are also of
      interest to our current understanding of quantum-classical correspondence
      considering that the KHM and ORDKR model have exactly the same classical limit
      after a simple canonical transformation.

PMID- 24329345
TI  - Electro-osmosis of electrorheological fluids.
AB  - Electrorheological fluids are suspensions that are characterized by a strong
      functional dependence of the constitutive behavior of the fluids on the electric
      field. In this work, we consider electro-osmosis of an electrorheological fluid
      through a channel where a transverse, nonuniform electric field is spontaneously
      induced due to the presence of an electric double layer that is manifested due to
      surface charge density at the channel wall. We reveal a nonlinear interplay
      between the applied electric field, the induced electric field, and the observed
      flow profiles, which is fundamentally distinctive from other types of nonlinear
      electrokinetic effects that have been extensively discussed in the literature, in
      a sense that here an interaction between the applied electric field, the induced
      electric field, and the dependence of the rheology on the resultant electric
      field happens to be the focal source of nonlinearity in the observed phenomena.
      We analyze the electro-osmotic flow control through the exploitation of a
      combined nonlinear interplay of the driving electrokinetic forces and the
      resistive viscous interactions, which gives rise to distinctive flow regimes as
      compared to those realized in cases of either Newtonian fluids or non-Newtonian
      fluids having electric-field-independent flow rheology. 

PMID- 24329346
TI  - Shear wave instability for electrified falling films.
AB  - The effect of an electric field on the shear wave instability pertaining to a
      gravity driven conducting liquid film is studied based on the Chebyshev-Tau
      method. The shear wave appears at very large values of the Reynolds number when
      the inclination angle is sufficiently small. The presence of an electric field
      shows peculiar behavior on the critical Reynolds number corresponding to the
      shear mode. It suppresses shear wave instability through the amplification of the
      critical Reynolds number and leads to a nontrivial stabilizing effect when
      inclination angle B>=3'. On the other hand, the reduction of the critical
      Reynolds number is found if the inclination angle is further lowered in
      magnitude.

PMID- 24329347
TI  - Radial viscous fingering: wetting film effects on pattern-forming mechanisms.
AB  - We consider the interfacial motion between two immiscible viscous fluids in the
      confined geometry of a radial Hele-Shaw cell. In this framework, we investigate
      the influence of a thin wetting film trailing behind the displaced fluid on the
      linear and weakly nonlinear dynamics of the system. More specifically, we examine
      how the interface instability and the pattern formation mechanisms of finger tip
      splitting and finger competition are affected by the presence of such a film in
      the low capillary number limit. Our theoretical analysis is carried out by
      employing a mode-coupling theory, which allows analytic assess to wetting-induced
      changes in pattern morphology at the onset of nonlinearities. 

PMID- 24329348
TI  - History independence of steady state in simultaneous two-phase flow through two
      dimensional porous media.
AB  - It is well known that the transient behavior during drainage or imbibition in
      multiphase flow in porous media strongly depends on the history and initial
      condition of the system. However, when the steady-state regime is reached and
      both drainage and imbibition take place at the pore level, the influence of the
      evolution history and initial preparation is an open question. Here, we present
      an extensive experimental and numerical work investigating the history dependence
      of simultaneous steady-state two-phase flow through porous media. Our
      experimental system consists of a Hele-Shaw cell filled with glass beads which we
      model numerically by a network of disordered pores transporting two immiscible
      fluids. From measurements of global pressure evolution, histograms of saturation,
      and cluster-size distributions, we find that when both phases are flowing through
      the porous medium, the steady state does not depend on the initial preparation of
      the system or on the way it has been reached. 

PMID- 24329349
TI  - Steady and transient thin-jet flow of a viscoelastic fluid.
AB  - Steady and transient two-dimensional thin-jet flow of a viscoelastic is examined
      theoretically. The influence of inertia, elasticity, and gravity is emphasized.
      The fluid is assumed to emerge from a vertical channel and to be driven by a
      pressure gradient and/or gravity. The boundary-layer equations are generalized
      for a viscoelastic thin film obeying the Oldroyd-B constitutive model. In
      contrast to the commonly used depth-averaging solution method, the strong
      nonlinearities are preserved in the present formulation as the viscoelastic
      boundary-layer equations are solved by expanding the flow field in terms of
      orthonormal shape functions. It is found that elasticity and gravity have the
      most profound effect on the steady state as well as the transient behavior of the
      viscoelastic film. The initial conditions strongly determine the stability of the
      film, which for all transient cases examined were shown to be stable despite the
      presence of initial instabilities. 

PMID- 24329350
TI  - Interfacial elastic fingering in Hele-Shaw cells: a weakly nonlinear study.
AB  - We study a variant of the classic viscous fingering instability in Hele-Shaw
      cells where the interface separating the fluids is elastic, and presents a
      curvature-dependent bending rigidity. By employing a second-order mode-coupling
      approach we investigate how the elastic nature of the interface influences the
      morphology of emerging interfacial patterns. This is done by focusing our
      attention on a conventionally stable situation in which the fluids involved have
      the same viscosity. In this framework, we show that the inclusion of nonlinear
      effects plays a crucial role in inducing sizable interfacial instabilities, as
      well as in determining the ultimate shape of the pattern-forming structures.
      Particularly, we have found that the emergence of either narrow or wide fingers
      can be regulated by tuning a rigidity fraction parameter. Our weakly nonlinear
      findings reinforce the importance of the so-called curvature weakening effect,
      which favors the development of fingers in regions of lower rigidity. 

PMID- 24329351
TI  - Bifurcation from stable holes to replicating holes in vibrated dense suspensions.
AB  - In vertically vibrated starch suspensions, we observe bifurcations from stable
      holes to replicating holes. Above a certain acceleration, finite-amplitude
      deformations of the vibrated surface continue to grow until void penetrates fluid
      layers, and a hole forms. We studied experimentally and theoretically the
      parameter dependence of the holes and their stabilities. In suspensions of small
      dispersed particles, the circular shapes of the holes are stable. However, we
      find that larger particles or lower surface tension of water destabilize the
      circular shapes; this indicates the importance of capillary forces acting on the
      dispersed particles. Around the critical acceleration for bifurcation, holes show
      intermittent large deformations as a precursor to hole replication. We applied a
      phenomenological model for deformable domains, which is used in reaction
      diffusion systems. The model can explain the basic dynamics of the holes, such as
      intermittent behavior, probability distribution functions of deformation, and
      time intervals of replication. Results from the phenomenological model match the
      linear growth rate below criticality that was estimated from experimental data. 

PMID- 24329352
TI  - Experimetal study of a freely falling plate with an inhomogeneous mass
      distribution.
AB  - A homogeneous thin plate often flutters while falling through a fluid under
      gravity. The center of gravity of the plate moves back-and-forth horizontally and
      the plate tilting angle oscillates symmetrically from the horizontal. Here we
      show that such a scenario is qualitatively changed for a plate with noncoinciding
      centers of gravity and buoyancy due to an inhomogeneous mass distribution.
      Mismatch of the centers causes an external torque that breaks the symmetry of
      rotational motion, shifts the mean tilting position from the horizontal, and
      leads to a net horizontal plate displacement. In laboratory experiments with a
      Reynolds number around 1500, we found that the net horizontal displacement scales
      linearly with the separation between the centers up to a critical value, beyond
      which the plate falls vertically in an edge-on configuration with the heavier
      side downward. Experimental results are compared to predictions of a quasi-steady
      numerical model. Our work demonstrates that motion of freely moving objects in a
      fluid depends sensitively on external torques, which potentially can be used as
      an effective control method. 

PMID- 24329353
TI  - Transition of the scaling law in inverse energy cascade range caused by a
      nonlocal excitation of coherent structures observed in two-dimensional turbulent
      fields.
AB  - We numerically investigate the inverse energy cascade range of two-dimensional
      Navier-Stokes turbulence. Our focus is on the universality of the Kolmogorov's
      phenomenology. In our direct numerical simulations, two types of forcing
      processes, the random forcing and the deterministic forcing, are employed besides
      the systematically varied numerical parameters. We first calculate the two
      dimensional Navier-Stokes equations and confirm that results in the quasi steady
      state are consistent with the classical phenomenology for both types of forcing
      processes. It is also found that the difference in forcing process appears after
      the inverse energy cascade range reaches the system size; the dipole coherent
      vortices emerge and grow only when the random forcing is adopted. Then we add a
      large-scale drag term to the Navier-Stokes equations to obtain the statistically
      stationary state. When the random forcing is used, the scaling exponent of the
      energy spectrum in the stationary state starts to differ from the predicted -5/3
      in the inverse energy cascade range as the infrared Reynolds number Re(d)
      increases, where Re(d) is defined as k(f)/k(d) with the forcing wave number k(f)
      and the large-scale drag wave number k(d). That can be interpreted as a
      transition phenomenon in which the local maximum vorticity grows like an order
      parameter caused by excitation of strong coherent vortices. Strong coherent
      vortices emerge and grow after the quasi steady state and destroy the scaling law
      when Re(d) is over a critical value. These coherent vortices are not due to the
      finite-size effect, unlike the dipole coherent vortices. On the other hand, when
      the deterministic forcing is adopted, strong coherent vortices are hardly seen
      and the -5/3 scaling law holds independently of Re(d). We examine the cases of
      the combination of both types of forcing processes and find that formation of
      such coherent vortices is sensitive to the mechanism of the external forcing
      process as well as the numerical parameters. Several types of large-scale drag
      terms are also tested and their insignificant influence on these qualitative
      properties is revealed.

PMID- 24329354
TI  - Effect of metallic walls on dynamos generated by laminar boundary-driven flow in
      a spherical domain.
AB  - We present a numerical study of dynamo action in a conducting fluid encased in a
      metallic spherical shell. Motions in the fluid are driven by differential
      rotation of the outer metallic shell, which we refer to as "the wall." The two
      hemispheres of the wall are held in counter-rotation, producing a steady,
      axisymmetric interior flow consisting of differential rotation and a two-cell
      meridional circulation with radial inflow in the equatorial plane. From previous
      studies, this type of flow is known to maintain a stationary equatorial dipole by
      dynamo action if the magnetic Reynolds number is larger than about 300 and if the
      outer boundary is electrically insulating. We vary independently the thickness,
      electrical conductivity, and magnetic permeability of the wall to determine their
      effect on the dynamo action. The main results are the following: (a) Increasing
      the conductivity of the wall hinders the dynamo by allowing eddy currents within
      the wall, which are induced by the relative motion of the equatorial dipole field
      and the wall. This processes can be viewed as a skin effect or, equivalently, as
      the tearing apart of the dipole by the differential rotation of the wall, to
      which the field lines are anchored by high conductivity. (b) Increasing the
      magnetic permeability of the wall favors dynamo action by constraining the
      magnetic field lines in the fluid to be normal to the wall, thereby decoupling
      the fluid from any induction in the wall. (c) Decreasing the wall thickness
      limits the amplitude of the eddy currents, and is therefore favorable for dynamo
      action, provided that the wall is thinner than the skin depth. We explicitly
      demonstrate these effects of the wall properties on the dynamo field by deriving
      an effective boundary condition in the limit of vanishing wall thickness. 

PMID- 24329355
TI  - Kinematic dynamo action in square and hexagonal patterns.
AB  - We consider kinematic dynamo action in rapidly rotating Boussinesq convection
      just above onset. The velocity is constrained to have either a square or a
      hexagonal pattern. For the square pattern, large-scale dynamo action is observed
      at onset, with most of the magnetic energy being contained in the horizontally
      averaged component. As the magnetic Reynolds number increases, small-scale dynamo
      action becomes possible, reducing the overall growth rate of the dynamo. For the
      hexagonal pattern, the breaking of symmetry between up and down flows results in
      an effective pumping velocity. For intermediate rotation rates, this additional
      effect can prevent the growth of any mean-field dynamo, so that only a small
      scale dynamo is eventually possible at large enough magnetic Reynolds number. For
      very large rotation rates, this pumping term becomes negligible, and the dynamo
      properties of square and hexagonal patterns are qualitatively similar. These
      results hold for both perfectly conducting and infinite magnetic permeability
      boundary conditions. 

PMID- 24329356
TI  - Information content of turbulence.
AB  - We treat a turbulent velocity field as a message in the same way as a book or a
      picture. All messages can be described by their entropy per symbol h, defined as
      in Shannon's theory of communication. In a turbulent flow, as the Reynolds number
      Re increases, more correlated degrees of freedom are excited and participate in
      the turbulent cascade. Experiments in a turbulent soap film suggest that the
      spatial entropy density h is a decreasing function of Re, namely
      h[proportionality]-logRe + const. In the logistic map, also analyzed here,
      increasing the control parameter r increases h. A modified logistic map with
      additional coupling to past iterations suggests the significance of correlations.

PMID- 24329357
TI  - Temperature dependence of capillary dynamics: a multiphase and multicomponent
      adiabatic approach.
AB  - We present an analysis of the effect of the temperature on the flow of multiphase
      systems made of multiple miscible components in uniform cylindrical capillaries
      in adiabatic conditions. The temperature was explicitly included in the dynamic
      contact angle, tension at the three-phase contact line, and densities and
      viscosities of the fluids. The mathematical framework accounted for conservative
      forces (gravity, inertial, and interfacial tensions), nonconservative forces
      (viscous dissipation), and fluid retardation effects in the reservoirs at the two
      capillary ends. Temperature-dependent flow regimes ranged from nonoscillatory to
      oscillatory in a two-phase binary liquid (water-ethanol) system and in a two
      phase pure liquid (ether) system. The Ca-Bo orbits highlighted dynamic attractors
      that depended on specific system characteristics as well as temperature. We
      conclude that temperature alone expresses and important role in the dynamical
      characteristics of capillary rise flow around its equilibrium. 

PMID- 24329358
TI  - Origins of the k(-2) spectrum in decaying Taylor-Green magnetohydrodynamic
      turbulent flows.
AB  - We investigate the origins of k(-2) spectrum in a decaying Taylor-Green
      magnetohydrodynamic flow with zero large scale magnetic flux that was reported by
      Lee et al. [Phys. Rev. E 81, 016318 (2010)]. So far, a possible candidate for
      this scaling exponent has been the weak turbulence phenomenology. From our
      numerical simulations, we observe that current sheets in the magnetic Taylor
      Green flow are formed in regions of magnetic discontinuities. Based on this
      observation and by studying the influence of the current sheets on the energy
      spectrum, using a filtering technique, we argue that the discontinuities are
      responsible for the -2 power law scaling of the energy spectra of this flow.

PMID- 24329359
TI  - Electrowetting-driven oscillating drops sandwiched between two substrates.
AB  - Drops sandwiched between two substrates are often found in lab-on-chip devices
      based on digital microfluidics. We excite azimuthal oscillations of such drops by
      periodically modulating the contact line via ac electrowetting. By tuning the
      frequency of the applied voltage, several shape modes can be selected one by one.
      The frequency of the oscillations is half the frequency of the contact angle
      modulation by electrowetting, indicating a parametric excitation. The drop
      response to sinusoidal driving deviates substantially from sinusoidal behavior in
      a "stop and go" fashion. Although our simple theoretical model describes the
      observed behavior qualitatively, the resonances appear at lower frequencies than
      expected. Moreover, the oscillations produce a nonperiodic fluid transport within
      the drop with a typical velocity of 1 mm/s. In digital microfluidic devices,
      where the typical drop size is less than 1 mm, this flow can result in very fast
      mixing on the spot. 

PMID- 24329360
TI  - Topology of hydrothermal waves in liquid bridges and dissipative structures of
      transported particles.
AB  - High-resolution three-dimensional numerical simulations are carried out for
      hydrothermal waves in a thermocapillary liquid bridge with Prandtl number Pr=4
      and length-to-radius aspect ratio Gamma=0.66. The flow topology is analyzed using
      Poincare sections in a frame of reference co-rotating with the phase velocity of
      the wave. We find regions of regular and chaotic motion. The regular regions are
      shown to be of key importance for dissipative structures of transported
      particles. Suspended particles which are passively advected in the bulk, but
      experience dissipation in a thin layer below the free surface, can rapidly form
      dissipative structures, also called particle accumulation structures. The shape
      and the formation time of the particulate structures are determined by the
      location of the invariant tori of the flow field with respect to the sub-surface
      layer in which the dissipation of the particle motion acts. The results from a
      hard-wall particle-free-surface interaction model are in good agreement with
      experimental observations. 

PMID- 24329361
TI  - Generalized vortex model for the inverse cascade of two-dimensional turbulence.
AB  - We generalize Kirchhoff's point vortex model of two-dimensional fluid motion to a
      rotor model which exhibits an inverse cascade by the formation of rotor clusters.
      A rotor is composed of two vortices with like-signed circulations glued together
      by an overdamped spring. The model is motivated by a treatment of the vorticity
      equation representing the vorticity field as a superposition of vortices with
      elliptic Gaussian shapes of variable widths, augmented by a suitable forcing
      mechanism. The rotor model opens up the way to discuss the energy transport in
      the inverse cascade on the basis of dynamical systems theory. 

PMID- 24329362
TI  - Onset of convection in a finite two-dimensional container due to unipolar
      injection of ions.
AB  - This work addresses the stability of a two-dimensional plane layer of a
      dielectric liquid enclosed in wall bounded cavities of different aspect ratios
      and subjected to unipolar injection of ions. Numerical simulations have been
      conducted to investigate the effect of lateral walls, especially in the
      development of the electroconvective instability. It is found that an unexpected
      change of the bifurcation nature occurs for certain cavity aspect ratios. We show
      that above the linear stability threshold for the rest state a supercritical
      bifurcation arises. This bifurcation takes place at a given value T(c1) of the
      parameter T (the electric Rayleigh number). Then, a second subcritical
      bifurcation occurs at a second threshold T(c2), featuring a typical hysteresis
      loop with an associated nonlinear criterion T(f), which is very characteristic of
      the Coulomb-driven convection. This behavior has been confirmed by different
      numerical codes based on different numerical methods. The physical mechanism
      which leads to this situation is analyzed and discussed. The evolution of the
      bifurcation diagrams with the aspect ratio of the cavity is also provided and
      analyzed.

PMID- 24329363
TI  - Experimental observations of Soret-driven convection in the transient diffusive
      boundary layer.
AB  - The onset of transient Soret-driven convection is investigated experimentally in
      a colloidal suspension of thermosensitive nanoparticles by the shadowgraph
      technique and by particle tracking observations. From the shadowgraph images, the
      concentration profile is reconstructed, giving evidence of a convective motion
      inside the transient boundary layer. Furthermore, the latency times for the
      convection onset are extracted from the measurements. The results point out that
      particle tracking is superior to the shadowgraph method for detecting the onset
      of convection. The onset latency times obtained from these experiments obey
      scaling laws which are in accordance with the predictions from theoretical
      treatments. 

PMID- 24329364
TI  - Electrohydrodynamics within the electrical double layer in the presence of finite
      temperature gradients.
AB  - A wide spectrum of electrokinetic studies is modeled as isothermal ones to
      expedite analysis even when such conditions may be extremely difficult to realize
      in practice. Going beyond the isothermal paradigm, we address here the case of
      flow induced electrohydrodynamics, commonly streaming potential flows, in a
      situation where finite temperature gradients do exist. By way of analyzing a
      model problem of flow through a narrow parallel-plate channel, we show that the
      temperature gradients applied at the channel walls may have a significant effect
      on the streaming potential, and, consequently, on the flow itself. Our model
      takes into consideration all the pertinent phenomenological aspects stemming from
      the imposed thermal gradients, such as the Soret effect, the thermoelectric
      effect, and the electrothermal effect, by a full-fledged coupling among the
      electric potential, the ionic species distribution, the fluid velocity and the
      local fluid temperature fields, without resorting to ad hoc simplifications. We
      expect this expository study to contribute significantly towards more
      sophisticated future endeavors in actual development of micro- and nano-devices
      for applications simultaneously involving thermal management and electrokinetic
      effects. 

PMID- 24329365
TI  - Three-dimensional dynamics of oblate and prolate capsules in shear flow.
AB  - We study computationally the dynamics of oblate and prolate spheroidal capsules
      in simple shear flow with small inertia for a range of dimensionless shear rates.
      The capsule is modelled as a liquid droplet enclosed by a hyperelastic membrane,
      and its equatorial plane is initially tilted out of the plane of shear. We find,
      at low shear rates, the well-accepted tumbling motion is not always stable for
      both oblate and prolate capsules. For an oblate capsule, the dominant stable
      modes for increasing dimensionless shear rate are as follows: rolling with the
      equatorial plane staying in the plane of shear, precessing following Jeffery's
      orbit [Proc. R. Soc. London A 102, 161 (1922)], and tumbling. Interestingly, the
      order of modes is reversed for a prolate capsule: tumbling, precessing, and
      rolling with increasing dimensionless shear rate. At transitional regimes, we
      find the stable motion of a capsule can depend on its initial titled angle, even
      at the same shear rate. At high dimensionless shear rates, a spheroidal capsule
      undergoes a complicated oscillating-swinging motion: Its major axis oscillates
      about the plane of shear in addition to the swinging about a mean angle with flow
      direction found previously, and the amplitudes of both oscillations decrease when
      increasing the dimensionless shear rate towards a steady tank treading motion
      asymptotically. We summarize the results in phase diagrams and discuss the
      reorientation of both oblate and prolate capsules in a wide range of
      dimensionless shear rates. 

PMID- 24329366
TI  - Dislocation dynamics during plastic deformations of complex plasma crystals.
AB  - The internal structures of most periodic crystalline solids contain defects. This
      affects various important mechanical and thermal properties of crystals. Since it
      is very difficult and expensive to track the motion of individual atoms in real
      solids, macroscopic model systems, such as complex plasmas, are often used.
      Complex plasmas consist of micrometer-sized grains immersed into an ion-electron
      plasma. They exist in solidlike, liquidlike, and gaseouslike states and exhibit a
      range of nonlinear and dynamic effects, most of which have direct analogies in
      solids and liquids. Slabs of a monolayer hexagonal complex plasma were subjected
      to a cycle of uniaxial compression and decompression of large amplitudes to
      achieve plastic deformations, both in experiments and simulations. During the
      cycle, the internal structure of the lattice exhibited significant
      rearrangements. Dislocations (point defects) were generated and displaced in the
      stressed lattice. They tended to glide parallel to their Burgers vectors under
      load. It was found that the deformation cycle was macroscopically reversible but
      irreversible at the particle scale. 

PMID- 24329367
TI  - Energy loss and Z oscillations of atomic beams in plasmas.
AB  - We apply a semiclassical partial-wave-scattering method based on the Wentzel
      Kramers-Brillouin approximation to study the transport cross section and the
      energy loss of neutral or ionized atomic beams in plasmas. This approach
      reproduces the exact quantum result in a satisfactory manner, even in several
      extreme conditions of plasma densities and temperatures, and agrees with the
      results of linear or perturbative calculations for bare ions in the appropriate
      limits. We pay special attention to low projectile speeds where strong
      oscillations in the transport cross section and energy loss-as a function of
      projectile's atomic number-are observed. We study these oscillatory phenomena
      varying the projectile speed and its ionization degree and the plasma temperature
      and density. We analyze in physical terms these effects and present a diagram of
      plasma conditions showing the regions where these oscillations may occur for both
      neutral and ionized beams. 

PMID- 24329368
TI  - Electron magnetohydrodynamics: dynamics and turbulence.
AB  - We consider dynamics and turbulent interaction of whistler modes within the
      framework of inertialess electron magnetohydrodynamics (EMHD). We argue that
      there is no energy principle in EMHD: any stationary closed configuration is
      neutrally stable. On the other hand, the relaxation principle, the long term
      evolution of a weakly dissipative system towards Taylor-Beltrami state, remains
      valid in EMHD. We consider the turbulent cascade of whistler modes. We show that
      (i) harmonic whistlers are exact nonlinear solutions; (ii) collinear whistlers do
      not interact (including counterpropagating); (iii) waves with the same value of
      the wave vector k(1)=k(2) do not interact; (iv) whistler modes have a dispersion
      that allows a three-wave decay, including into a zero frequency mode; (v) the
      three-wave interaction effectively couples modes with highly different wave
      numbers and propagation angles. In addition, linear interaction of a whistler
      with a single zero mode can lead to spatially divergent structures via parametric
      instability. All these properties are drastically different from MHD, so that the
      qualitative properties of the Alfven turbulence can not be transferred to the
      EMHD turbulence. We derive the Hamiltonian formulation of EMHD, and using
      Bogoliubov transformation reduce it to the canonical form; we calculate the
      matrix elements for the three-wave interaction of whistlers. We solve numerically
      the kinetic equation and show that, generally, the EMHD cascade develops within a
      broad range of angles, while transiently it may show anisotropic, nearly two
      dimensional structures. Development of a cascade depends on the forcing
      (nonuniversal) and often fails to reach a steady state. Analytical estimates
      predict the spectrum of magnetic fluctuations for the quasi-isotropic cascade
      [proportionality]k(-2). The cascade remains weak (not critically balanced). The
      cascade is UV local, while the infrared locality is weakly (logarithmically)
      violated.

PMID- 24329369
TI  - Geometrical feature of the scaling behavior of the limit-point pressure of
      inflated hyperelastic membranes.
AB  - The occurrence of the limit-point instability is an intriguing phenomenon
      observed during stretching of hyperelastic membranes. In toy rubber balloons,
      this phenomenon may be experienced in the sudden reduction in the level of
      difficulty of blowing the balloon accompanied by its rapid inflation. The present
      paper brings out a link between the geometry and strain-hardening parameter of
      the membrane, and the occurrence of the limit-point instability. Inflation of
      membranes with different geometries and boundary conditions is considered, and
      the corresponding limit-point pressures are obtained for different strain
      hardening parameter values. Interestingly, it is observed that the limit-point
      pressure for the different geometries is inversely proportional to a geometric
      parameter of the uninflated membrane. This dependence is shown analytically,
      which can be extended to a general membrane geometry. More surprisingly, the
      proportionality constant has a power-law dependence on the nondimensional
      material strain-hardening parameter. The constants involved in the power-law
      relation are universal constants for a particular membrane geometry. 

PMID- 24329370
TI  - Wide vector solitons in systems with time- and space-modulated nonlinearities.
AB  - In this work we apply point canonical transformations to solve some classes of
      two coupled nonautonomous nonlinear Schrodinger equations with specific cubic and
      quintic-time- and space-dependent-nonlinearities. The method applied here allows
      us to find a class of wide localized (in space) vector soliton solutions of
      nonautonomous nonlinear Schrodinger equations. The vector solitons found here can
      be applied to theoretical studies of Bose-condensed atoms in two different
      internal states and of ultrashort pulse propagation in optical fibers with
      focusing and defocusing nonlinearities. 

PMID- 24329371
TI  - Modulational instability and breathing motion in the two-dimensional nonlinear
      Schrodinger equation with a one-dimensional harmonic potential.
AB  - Modulational instability and breathing motion are studied in the two-dimensional
      nonlinear Schrodinger (NLS) equation trapped by the one-dimensional harmonic
      potential. The trapping potential is uniform in the y direction and the wave
      function is confined in the x direction. A breathing motion appears when the
      initial condition is close to a stationary solution which is uniform in the y
      direction. The amplitude of the breathing motion is larger in the two-dimensional
      system than that in the corresponding one-dimensional system. Coupled equations
      of the one-dimensional NLS equation and two variational parameters are derived by
      the variational approximation to understand the amplification of the breathing
      motion qualitatively. On the other hand, there is a breathing solution in the x
      direction which is uniform in the y direction to the two-dimensional NLS
      equation. It is shown that the modulational instability along the y direction is
      suppressed when the breathing motion is sufficiently strong, even if the norm is
      above the critical value of the collapse. 

PMID- 24329372
TI  - Integrable aspects and soliton interaction for a generalized inhomogeneous
      Gardner model with external force in plasmas and fluids.
AB  - A generalized inhomogeneous Gardner model with an external force term is
      investigated which can govern the soliton propagation and interaction in the
      vicinity of the negative ion critical density for certain plasmas or of equal
      layer depths for stratified fluids. Integrable aspects including the Lax pair and
      the Gamma-Riccati-type Backlund transformation (Gamma-R BT) are presented under
      the Painleve conditions. By virtue of the Gamma-R BT, analytic one- or two
      soliton-like solutions with the inhomogeneous coefficients, external force term,
      eigenvalue in the Lax pair, and another parameter are obtained. Analytic analysis
      and graphic illustration imply that (1) the amplitude of a soliton is influenced
      by the quadratic and cubic nonlinear coefficients, the linear-damping
      coefficient, and the aforementioned eigenvalue; (2) the solitonic velocity is
      "controlled" by the inhomogeneous coefficients, the external force term, and the
      aforementioned eigenvalue and parameter; (3) the solitonic background is affected
      by the linear-damping coefficient, the external force term and the aforementioned
      parameter; and (4) the possibility of solitonic infection is dominated by the
      difference between eigenvalues. 

PMID- 24329373
TI  - Efficiency and time-dependent cross correlations in multivariable Monte Carlo
      updating.
AB  - We show that any Monte Carlo (MC) algorithm using joint updates of more than a
      single variable at each step produces time-shifted correlations between variables
      even if the equilibrium probabilities of the variables are independent. These
      spurious time-shifted correlations will affect both the magnitudes of correlation
      times and the values of optimal acceptance ratios. In particular, correlation
      times computed with local variables will not generally give the same predictions
      of efficiency or optimal acceptance ratios as those computed with global
      variables. Gelman, Roberts, and Gilks [Bayesian Statistics, edited by J. M.
      Bernardo, J. O. Berger, A. P. Dawid, and A. R. M. Smith, Vol. 5 (Oxford
      University Press, 1996), pp. 599-607] have used a local measure of efficiency to
      prove a theorem for global MC updating that predicts an optimal acceptance ratio
      of 0.234 as the number of variables goes to infinity. We show that global
      measures of efficiency can produce different, and arguably more appropriate,
      optimal acceptance ratios. More importantly, global updating is inherently far
      less efficient than updating variables separately or in small groups. We suggest
      that previously determined optimal acceptance ratios and their implications for
      practical applications should be reconsidered in the context of these findings. 

PMID- 24329374
TI  - Dynamically optimized Wang-Landau sampling with adaptive trial moves and
      modification factors.
AB  - The density of states of continuous models is known to span many orders of
      magnitudes at different energies due to the small volume of phase space near the
      ground state. Consequently, the traditional Wang-Landau sampling which uses the
      same trial move for all energies faces difficulties sampling the low-entropic
      states. We developed an adaptive variant of the Wang-Landau algorithm that very
      effectively samples the density of states of continuous models across the entire
      energy range. By extending the acceptance ratio method of Bouzida, Kumar, and
      Swendsen such that the step size of the trial move and acceptance rate are
      adapted in an energy-dependent fashion, the random walker efficiently adapts its
      sampling according to the local phase space structure. The Wang-Landau
      modification factor is also made energy dependent in accordance with the step
      size, enhancing the accumulation of the density of states. Numerical simulations
      show that our proposed method performs much better than the traditional Wang
      Landau sampling. 

PMID- 24329375
TI  - Diagnostics for insufficiencies of posterior calculations in Bayesian signal
      inference.
AB  - We present an error-diagnostic validation method for posterior distributions in
      Bayesian signal inference, an advancement of a previous work. It transfers
      deviations from the correct posterior into characteristic deviations from a
      uniform distribution of a quantity constructed for this purpose. We show that
      this method is able to reveal and discriminate several kinds of numerical and
      approximation errors, as well as their impact on the posterior distribution. For
      this we present four typical analytical examples of posteriors with incorrect
      variance, skewness, position of the maximum, or normalization. We show further
      how this test can be applied to multidimensional signals. 

PMID- 24329376
TI  - Lattice Boltzmann method coupled with the Oldroyd-B constitutive model for a
      viscoelastic fluid.
AB  - We developed a lattice Boltzmann method coupled with the Oldroyd-B constitutive
      equation to simulate a viscoelastic fluid. In this work, the flow field of the
      solvent is solved using an incompressible lattice Boltzmann Bhatnagar-Gross-Krook
      (BGK) model, while the advection operator of the polymer stress tensor is
      directly calculated with the help of the particle distribution functions.
      Specifically, we present a numerical scheme for the advection of the polymer
      stress tensor through the truncation of second-order Taylor expansion, which does
      not need to introduce the extra distribution functions and has better numerical
      accuracy. We consider two types of numerical tests to examine the performance of
      the presented method, including a two-dimensional (2D) channel flow and the 4:1
      contraction problem. Our numerical results for the 2D channel flow agree well
      with the analytical results and some experimental results reported in the
      previous studies. Moreover, the numerical results also indicate that the current
      method can capture some complex rheological behaviors of the 4:1 contraction
      flow. 

PMID- 24329377
TI  - Transfer-matrix approach for finite-difference time-domain simulation of periodic
      structures.
AB  - Optical properties of periodic structures can be calculated using the transfer
      matrix approach, which establishes a relation between amplitudes of the wave
      incident on a structure with transmitted or reflected waves. The transfer matrix
      can be used to obtain transmittance and reflectance spectra of finite periodic
      structures as well as eigenmodes of infinite structures. Traditionally,
      calculation of the transfer matrix is performed in the frequency domain and
      involves linear algebra. In this work, we present a technique for calculation of
      the transfer matrix using the finite-difference time-domain (FDTD) method and
      show the way of its implementation in FDTD code. To illustrate the performance of
      our technique we calculate the transmittance spectra for opal photonic crystal
      slabs consisting of multiple layers of spherical scatterers. Our technique can be
      used for photonic band structure calculations. It can also be combined with
      existing FDTD methods for the analysis of periodic structures at an oblique
      incidence, as well as for modeling point sources in a periodic environment. 

PMID- 24329378
TI  - Generating true minima in constrained variational formulations via modified
      Lagrange multipliers.
AB  - Variational principles are important in the investigation of large classes of
      physical systems. They can be used both as analytical methods as well as starting
      points for the formulation of powerful computational techniques such as dynamical
      optimization methods. Systems with charged objects in dielectric media and
      systems with magnetically active particles are important examples. In these
      examples and other important cases, the variational principles describing the
      system are required to obey a number of constraints. These constraints are
      implemented within the variational formulation by means of Lagrange multipliers.
      Such constrained variational formulations are in general not unique. For the
      application of efficient simulation methods, one must find specific formulations
      that satisfy a number of important conditions. An often required condition is
      that the functional be positive-definite, in other words, its extrema be actual
      minima. In this article, we present a general approach to attack the problem of
      finding, among equivalent variational functionals, those that generate true
      minima. The method is based on the modification of the Lagrange multiplier which
      allows us to generate large families of effective variational formulations
      associated with a single original constrained variational principle. We
      demonstrate its application to different examples and, in particular, to the
      important cases of Poisson and Poisson-Boltzmann equations. We show how to obtain
      variational formulations for these systems with extrema that are always minima. 

PMID- 24329379
TI  - Achieving tunable surface tension in the pseudopotential lattice Boltzmann
      modeling of multiphase flows.
AB  - In this paper, we aim to address an important issue about the pseudopotential
      lattice Boltzmann (LB) model, which has attracted much attention as a mesoscopic
      model for simulating interfacial dynamics of complex fluids, but suffers from the
      problem that the surface tension cannot be tuned independently of the density
      ratio. In the literature, a multirange potential was devised to adjust the
      surface tension [Sbragaglia et al., Phys. Rev. E 75, 026702 (2007)]. However, it
      was recently found that the density ratio of the system will be changed when the
      multirange potential is employed to adjust the surface tension. An alternative
      approach is therefore proposed in the present work. The basic strategy is to add
      a source term to the LB equation so as to tune the surface tension of the
      pseudopotential LB model. The proposed approach can guarantee that the adjustment
      of the surface tension does not affect the mechanical stability condition of the
      pseudopotential LB model, and thus provides a separate control of the surface
      tension and the density ratio. Meanwhile, it still retains the mesoscopic feature
      and the computational simplicity of the pseudopotential LB model. Numerical
      simulations are carried out for stationary droplets, capillary waves, and droplet
      splashing on a thin liquid film. The numerical results demonstrate that the
      proposed approach is capable of achieving a tunable surface tension over a very
      wide range and can keep the density ratio unchanged when adjusting the surface
      tension. 

PMID- 24329380
TI  - Exact transparent boundary condition for the three-dimensional Schrodinger
      equation in a rectangular cuboid computational domain.
AB  - We report an exact transparent boundary condition (TBC) on the surface of a
      rectangular cuboid for the three-dimensional (3D) time-dependent Schrodinger
      equation. It is obtained as a generalization of the well-known TBC for the 1D
      Schrodinger equation and of the exact TBC in the rectangular domain for the 3D
      parabolic wave equation, which we reported earlier. Like all other TBCs, it is
      nonlocal in time domain and relates the boundary transverse derivative of the
      wave function at any given time to the boundary values of the same wave function
      at all preceding times. We develop a discretization of this boundary condition
      for the implicit Crank-Nicolson finite difference scheme. Several numerical
      experiments demonstrate evolution of the wave function in free space as well as
      propagation through a number of 3D spherically symmetrical and asymmetrical
      barriers, and, finally, scattering off an asymmetrical 3D potential. The proposed
      boundary condition is simple and robust, and can be useful in computational
      quantum mechanics when an accurate numerical solution of the 3D Schrodinger
      equation is required. 

PMID- 24329381
TI  - Efficient parallelization of short-range molecular dynamics simulations on many
      core systems.
AB  - This article introduces a highly parallel algorithm for molecular dynamics
      simulations with short-range forces on single node multi- and many-core systems.
      The algorithm is designed to achieve high parallel speedups for strongly
      inhomogeneous systems like nanodevices or nanostructured materials. In the
      proposed scheme the calculation of the forces and the generation of neighbor
      lists are divided into small tasks. The tasks are then executed by a thread pool
      according to a dependent task schedule. This schedule is constructed in such a
      way that a particle is never accessed by two threads at the same time. Benchmark
      simulations on a typical 12-core machine show that the described algorithm
      achieves excellent parallel efficiencies above 80% for different kinds of systems
      and all numbers of cores. For inhomogeneous systems the speedups are strongly
      superior to those obtained with spatial decomposition. Further benchmarks were
      performed on an Intel Xeon Phi coprocessor. These simulations demonstrate that
      the algorithm scales well to large numbers of cores. 

PMID- 24329382
TI  - Multidimensional on-lattice higher-order models in the thermal lattice Boltzmann
      theory.
AB  - We present a set of uniform polynomial equations that provides multidimensional
      on-lattice higher-order models of the lattice Boltzmann theory while keeping
      compact the number of discrete velocities. As examples, we explicitly derive one
      , two-, and three-dimensional on-lattice models applicable to describing thermal
      compressible flows of the accuracy levels of the Navier-Stokes equations with
      smaller numbers of discrete velocities in comparison to the existing models. We
      demonstrate the accuracy and stability of the one-, two-, and three-dimensional
      models by using the Riemann problem. 

PMID- 24329383
TI  - Filter-matrix lattice Boltzmann model for microchannel gas flows.
AB  - The lattice Boltzmann method has been shown to be successful for microscale gas
      flows, and it has attracted significant research interest. In this paper, the
      recently proposed filter-matrix lattice Boltzmann (FMLB) model is first applied
      to study the microchannel gas flows, in which a Bosanquet-type effective
      viscosity is used to capture the flow behaviors in the transition regime. A
      kinetic boundary condition, the combined bounce-back and specular-reflection
      scheme with the second-order slip scheme, is also designed for the FMLB model. By
      analyzing a unidirectional flow, the slip velocity and the discrete effects
      related to the boundary condition are derived within the FMLB model, and a
      revised scheme is presented to overcome such effects, which have also been
      validated through numerical simulations. To gain an accurate simulation in a wide
      range of Knudsen numbers, covering the slip and the entire transition flow
      regimes, a set of slip coefficients with an introduced fitting function is
      adopted in the revised second-order slip boundary condition. The periodic and
      pressure-driven microchannel flows have been investigated by the present model in
      this study. The numerical results, including the velocity profile and the mass
      flow rate, as well as the nonlinear pressure distribution along the channel,
      agree fairly well with the solutions of the linearized Boltzmann equation, the
      direct simulation Monte Carlo results, the experimental data, and the previous
      results of the multiple effective relaxation lattice Boltzmann model. Also, the
      present results of the velocity profile and the mass flow rate show that the
      present model with the fitting function can yield improved predictions for the
      microchannel gas flow with higher Knudsen numbers in the transition flow regime. 

PMID- 24329384
TI  - Precise algorithm to generate random sequential addition of hard hyperspheres at
      saturation.
AB  - The study of the packing of hard hyperspheres in d-dimensional Euclidean space
      R^{d} has been a topic of great interest in statistical mechanics and condensed
      matter theory. While the densest known packings are ordered in sufficiently low
      dimensions, it has been suggested that in sufficiently large dimensions, the
      densest packings might be disordered. The random sequential addition (RSA) time
      dependent packing process, in which congruent hard hyperspheres are randomly and
      sequentially placed into a system without interparticle overlap, is a useful
      packing model to study disorder in high dimensions. Of particular interest is the
      infinite-time saturation limit in which the available space for another sphere
      tends to zero. However, the associated saturation density has been determined in
      all previous investigations by extrapolating the density results for nearly
      saturated configurations to the saturation limit, which necessarily introduces
      numerical uncertainties. We have refined an algorithm devised by us [S. Torquato,
      O. U. Uche, and F. H. Stillinger, Phys. Rev. E 74, 061308 (2006)] to generate RSA
      packings of identical hyperspheres. The improved algorithm produce such packings
      that are guaranteed to contain no available space in a large simulation box using
      finite computational time with heretofore unattained precision and across the
      widest range of dimensions (2<=d<=8). We have also calculated the packing and
      covering densities, pair correlation function g(2)(r), and structure factor S(k)
      of the saturated RSA configurations. As the space dimension increases, we find
      that pair correlations markedly diminish, consistent with a recently proposed
      "decorrelation" principle, and the degree of "hyperuniformity" (suppression of
      infinite-wavelength density fluctuations) increases. We have also calculated the
      void exclusion probability in order to compute the so-called quantizer error of
      the RSA packings, which is related to the second moment of inertia of the average
      Voronoi cell. Our algorithm is easily generalizable to generate saturated RSA
      packings of nonspherical particles.

PMID- 24329385
TI  - Effective diffusion coefficient of a Brownian particle in a periodically expanded
      conical tube.
AB  - Diffusion in a tube of periodically varying diameter occurs slower than that in a
      cylindrical tube because diffusing particles get trapped in wells of the periodic
      entropy potential which is due to variation of the tube cross-section area. To
      quantify the slowdown one has to establish a relation between the effective
      diffusion coefficient of the particle and the tube geometry, which is a very
      complicated problem. Here we show how to overcome the difficulties in the case of
      a periodically expanded conical tube, where we find an approximate solution for
      the effective diffusion coefficient as a function of the parameters determining
      the tube geometry. 

PMID- 24329386
TI  - Simplified approach for calculating moments of action for linear reaction
      diffusion equations.
AB  - The mean action time is the mean of a probability density function that can be
      interpreted as a critical time, which is a finite estimate of the time taken for
      the transient solution of a reaction-diffusion equation to effectively reach
      steady state. For high-variance distributions, the mean action time
      underapproximates the critical time since it neglects to account for the spread
      about the mean. We can improve our estimate of the critical time by calculating
      the higher moments of the probability density function, called the moments of
      action, which provide additional information regarding the spread about the mean.
      Existing methods for calculating the nth moment of action require the solution of
      n nonhomogeneous boundary value problems which can be difficult and tedious to
      solve exactly. Here we present a simplified approach using Laplace transforms
      which allows us to calculate the nth moment of action without solving this family
      of boundary value problems and also without solving for the transient solution of
      the underlying reaction-diffusion problem. We demonstrate the generality of our
      method by calculating exact expressions for the moments of action for three
      problems from the biophysics literature. While the first problem we consider can
      be solved using existing methods, the second problem, which is readily solved
      using our approach, is intractable using previous techniques. The third problem
      illustrates how the Laplace transform approach can be used to study coupled
      linear reaction-diffusion equations. 

PMID- 24329387
TI  - Propagator for the Fokker-Planck equation with an arbitrary diffusion
      coefficient.
AB  - We consider a general diffusion process that is force-free and the corresponding
      Fokker-Planck equation with an arbitrary diffusion coefficient. A propagator for
      the Fokker-Planck equation of the Stratonovich form is obtained based on random
      walks. The characteristics of the solution are analyzed. 

PMID- 24329388
TI  - Hydrodynamic effects in the measurement of interparticle forces in nematic
      colloids.
AB  - We propose improved measurement methods of interparticle force between nematic
      colloids. Although various methods have been utilized for the force measurement,
      the comparison between the forces obtained by different methods has not been
      reported. In the frequently used method called the "free-release" method, the
      hydrodynamic interaction between moving particles has a serious influence on the
      measurement. In this study we modified those measurement methods by taking the
      long-ranged hydrodynamic interaction into account. The evaluated forces have been
      compared with that obtained by the dual beam "optical trap" method, which is free
      from the hydrodynamic effect. The agreement between them is quantitatively fairly
      good. 

PMID- 24329389
TI  - Single polymer gating of channels under a solvent gradient.
AB  - We study the effect of a gradient of solvent quality on the coil-globule
      transition for a polymer in a narrow pore. A simple self-attracting, self
      avoiding walk model of a polymer in solution shows that the variation in the
      strength of the interaction across the pore leads the system to go from one
      regime (good solvent) to the other (poor solvent) across the channel. This may be
      thought to be analogous to thermophoresis, where the polymer goes from the hot
      region to the cold region under the temperature gradient. The behavior of short
      chains is studied using exact enumeration while the behavior of long chains is
      studied using transfer matrix techniques. The distribution of the monomer density
      across the layer suggests that a gatelike effect can be created, with potential
      applications as a sensor. 

PMID- 24329390
TI  - Importance of the Voronoi domain partition for position-jump reaction-diffusion
      processes on nonuniform rectilinear lattices.
AB  - Position-jump processes are used for the mathematical modeling of spatially
      extended chemical and biological systems with increasing frequency. A large
      subset of the literature concerning such processes is concerned with modeling the
      effect of stochasticity on reaction-diffusion systems. Traditionally,
      computational domains have been divided into regular voxels. Molecules are
      assumed well mixed within each of these voxels and are allowed to react with
      other molecules within the same voxel or to jump to neighboring voxels with
      predefined transition rates. For a variety of reasons implementing position-jump
      processes on irregular grids is becoming increasingly important. However, it is
      not immediately clear what form an appropriate irregular partition of the domain
      should take if it is to allow the derivation of mean molecular concentrations
      that agree with a given partial differential equation for molecular
      concentrations. It has been demonstrated, in one dimension, that the Voronoi
      domain partition is the appropriate method with which to divide the computational
      domain. In this Brief Report, we investigate theoretically the propriety of the
      Voronoi domain partition as an appropriate method to partition domains for
      position-jump models in higher dimensions. We also provide simulations of
      diffusion processes in two dimensions in order to corroborate our results. 

PMID- 24329391
TI  - Discrete-network versus modal representations of brain activity: why a sparse
      regions-of-interest approach can work for analysis of continuous dynamics.
AB  - The efficacy of the common practice of tracking brain dynamics using a few key
      regions of interest is explained via the fact that these regions are sensitive to
      underlying extended modes of activity, not just local dynamics. This underlines
      the inseparable interplay between modes and regions and reflects the reality that
      brain functions range from highly localized to highly extended. 

PMID- 24329392
TI  - Synchronized flow in oversaturated city traffic.
AB  - Based on numerical simulations with a stochastic three-phase traffic flow model,
      we reveal that moving queues (moving jams) in oversaturated city traffic dissolve
      at some distance upstream of the traffic signal while transforming into
      synchronized flow. It is found that, as in highway traffic [Kerner, Phys. Rev. E
      85, 036110 (2012)], such a jam-absorption effect in city traffic is explained by
      a strong driver's speed adaptation: Time headways (space gaps) between vehicles
      increase upstream of a moving queue (moving jam), resulting in moving queue
      dissolution. It turns out that at given traffic signal parameters, the stronger
      the speed adaptation effect, the shorter the mean distance between the signal
      location and the road location at which moving queues dissolve fully and
      oversaturated traffic consists of synchronized flow only. A comparison of the
      synchronized flow in city traffic found in this Brief Report with synchronized
      flow in highway traffic is made. 

PMID- 24329393
TI  - Absolute measurement of the total ion-drag force on a single plasma-confined
      microparticle at the void edge under microgravity conditions.
AB  - We present an absolute measurement of the total ion-drag force on one single
      microparticle at the edge of the dust free region in low pressure complex
      plasmas: the void. In order to do so, the particle confinement position was
      monitored as a function of the gas pressure for two particle sizes under normal
      gravity conditions and under microgravity conditions during parabolic flights. At
      the border of the void, the ion-drag force on a particle with a radius of 4.90
      MUm appeared to be (3.6+/-0.3)*10(-12) N.

PMID- 24329394
TI  - Comment on "Hydrodynamics of fractal continuum flow" and "Map of fluid flow in
      fractal porous medium into fractal continuum flow".
AB  - In two recent papers [Phys. Rev. E 85, 025302(R) (2012) and Phys. Rev. E 85,
      056314 (2012)], the authors proposed fractal continuum hydrodynamics and its
      application to model fluid flows in fractally permeable reservoirs. While in
      general providing a certain advancement of continuum mechanics modeling of
      fractal media to fluid flows, some results and statements to previous works need
      clarification. We first show that the nonlocal character those authors alleged in
      our paper [Proc. R. Soc. A 465, 2521 (2009)] actually does not exist; instead,
      all those works are in the same general representation of derivative operators
      differing by specific forms of the line coefficient c(1). Next, the claimed
      generalization of the volumetric coefficient c(3) is, in fact, equivalent to
      previously proposed product measures when considering together the separate
      decomposition of c(3) on each coordinate. Furthermore, the modified Jacobian
      proposed in the two commented papers does not relate the volume element between
      the current and initial configurations, which henceforth leads to a correction of
      the Reynolds' transport theorem. Finally, we point out that the asymmetry of the
      Cauchy stress tensor resulting from the conservation of the angular momentum must
      not be ignored; this aspect motivates a more complete formulation of fractal
      continuum models within a micropolar framework.

PMID- 24329395
TI  - Reply to "Comment on 'Hydrodynamics of fractal continuum flow' and 'Map of fluid
      flow in fractal porous medium into fractal continuum flow'".
AB  - The aim of this Reply is to elucidate the difference between the fractal
      continuum models used in the preceding Comment and the models of fractal
      continuum flow which were put forward in our previous articles [Phys. Rev. E 85,
      025302(R) (2012); 85, 056314 (2012)]. In this way, some drawbacks of the former
      models are highlighted. Specifically, inconsistencies in the definitions of the
      fractal derivative, the Jacobian of transformation, the displacement vector, and
      angular momentum are revealed. The proper forms of the Reynolds' transport
      theorem and angular momentum principle for the fractal continuum are reaffirmed
      in a more illustrative manner. Consequently, we emphasize that in the absence of
      any internal angular momentum, body couples, and couple stresses, the Cauchy
      stress tensor in the fractal continuum should be symmetric. Furthermore, we
      stress that the approach based on the Cartesian product measured and used in the
      preceding Comment cannot be employed to study the path-connected fractals, such
      as a flow in a fractally permeable medium. Thus, all statements of our previous
      works remain unchallenged. 

PMID- 24329396
TI  - A microscopic evaluation of collagen-bilirubin interactions: in vitro surface
      phenomenon.
AB  - This study is carried out to understand the morphology variations of collagen I
      matrices influenced by bilirubin. The characteristics of bilirubin interaction
      with collagen ascertained using various techniques like XRD, CLSM, fluorescence,
      SEM and AFM. These techniques are used to understand the distribution, expression
      and colocalization patterns of collagen-bilirubin complexes. The present
      investigation mimic the in vivo mechanisms created during the disorder condition
      like jaundice. Fluorescence technique elucidates the crucial role played by
      bilirubin deposition and interaction during collagen organization. Influence of
      bilirubin during collagen fibrillogenesis and banding patterns are clearly
      visualize using SEM. As a result, collagen-bilirubin complex provides different
      reconstructed patterns because of the influence of bilirubin concentration.
      Selectivity, specificity and spatial organization of collagen-bilirubin are
      determined through AFM imaging. Consequently, it is observed that the morphology
      and quantity of the bilirubin binding to collagen varied by the concentrations
      and the adsorption rate in protein solutions. Microscopic studies of collagen
      bilirubin interaction confirms that bilirubin influence the fibrillogenesis and
      alter the rate of collagen organization depending on the bilirubin concentration.
      This knowledge helps to develop a novel drug to inhibit the interface point of
      interaction between collagen and bilirubin. 

PMID- 24329397
TI  - Severe renal failure and hyperammonemia in a newborn with propionic acidemia:
      effects of treatment on the clinical course.
AB  - Neonatal-onset propionic acidemia (PA), the most common form, is characterized by
      poor feeding, vomiting, and somnolence in the first days of life in a previously
      healthy infant, followed by lethargy, seizures, and can progress to coma if not
      identified and treated appropriately. It is frequently accompanied by metabolic
      acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias.
      PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that
      catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Herein, we report
      a case of 3-day-old neonate with PA presented with acute renal failure and
      metabolic acidosis was effectively treated by peritoneal dialysis and
      conventional methods.

PMID- 24329398
TI  - Use of electroconvulsive therapy in the Baltic states.
AB  - OBJECTIVES: While the use of electroconvulsive therapy (ECT) has been
      investigated worldwide, nothing is known about its use in the Baltic states. The
      purpose of this study was thus to explore ECT practice in the three Baltic
      countries. METHODS: A 21-item, semi-structured questionnaire was sent out to all
      psychiatric inpatient settings that provided ECT in 2010. RESULTS: In Lithuania,
      four services provided ECT in 2010. Only modified ECT with anaesthesia and muscle
      relaxation is performed in the country. In 2010, approximately 120 patients
      received ECT, i.e., 0.375 patients/10,000 population. Only two centres offer ECT
      in Latvia. The first centre treated only three patients with ECT in 2010, while
      the second centre six patients. In both centres outdated Soviet machines are
      used. The main indication for ECT was severe, malignant catatonia. ECT is
      practiced in five psychiatric facilities in Estonia. In 2010, it was used in the
      treatment of 362 patients (17% women) nationwide, i.e., 2.78 patients/10,000
      population. Only a senior psychiatrist may indicate ECT in Estonia and pregnancy
      is no contraindication. In 2010, the main indication for ECT was schizophrenia
      (47.8%). CONCLUSIONS: This 2010 survey revealed significant differences in the
      use and availability of ECT between the Baltic countries.

PMID- 24329399
TI  - Behavioral correlation with television watching and videogame playing among
      children in the United Arab Emirates.
AB  - OBJECTIVE: Television viewing and videogame use (TV/VG) appear to be associated
      with some childhood behavioral problems. There are no studies addressing this
      problem in the United Arab Emirates. METHODS: One hundred ninety-seven school
      children (mean age, 8.7 +/- 2.1 years) were assessed. Child Behavior Checklist
      (CBCL) subscale scores and socio-demographic characteristics were compared
      between children who were involved with TV/VG more than 2 hours/day and those
      involved less than 2 hours/day (the recommended upper limit by The American
      Academy of Pediatrics). RESULTS: Thirty-seven percent of children who were
      involved with TV/VG time of more than 2 hours/day scored significantly higher on
      CBCL syndrome scales of withdrawn, social problems, attention problems,
      delinquent behavior, aggressive behavior, internalizing problems, externalizing
      problems and the CBCL total scores compared with their counterparts. Moreover,
      these children were younger in birth order and had fewer siblings. After
      controlling for these confounders using logistic regression, we found that TV/VG
      time more than 2 hours/day was positively associated with withdrawn (p = 0.008),
      attention problem (p = 0.037), externalizing problems (p = 0.007), and CBCL total
      (p = 0.014). CONCLUSION: Involvement with TV/VG for more than 2 hours/day is
      associated with more childhood behavioral problems. Counteracting negative
      effects of the over-involvement with TV/VG in children requires increased
      parental awareness.

PMID- 24329400
TI  - Oral calcium pectinate-insulin nanoparticles: influences of alginate, sodium
      chloride and Tween 80 on their blood glucose lowering performance.
AB  - OBJECTIVE: Examine the formation of pectin-insulin nanoparticles and their blood
      glucose lowering properties. METHODS: The calcium pectinate nanoparticles were
      prepared by ionotropic gelation method, with alginate, sodium chloride or Tween
      80 as additive. Their in vitro physicochemical, drug release and in vivo blood
      glucose lowering characteristics were evaluated. KEY FINDINGS: Spherical calcium
      pectinate-insulin nanoparticles were characterized by size, zeta potential,
      insulin content and insulin association efficiency of 348.4 +/- 12.9 nm, -17.9 +/
      0.8 mV, 8.4 +/- 1.0% and 63.8 +/- 7.4%, respectively. They released less than
      25% insulin following 24 h in simulated intestinal medium and exhibited delayed
      blood glucose lowering effect in rats. Incorporation of solubilizer sodium
      chloride or Tween 80 into nanoparticles did not enhance blood glucose lowering
      capacity owing to sodium chloride reduced matrix insulin content and Tween 80
      interacted with water and had its blood glucose dilution effect negated.
      Combination of nanoparticles with alginate gel to allow prolonged intestinal
      residence and more insulin release did not enhance their blood glucose lowering
      capacity because of calcium alginate-cross-linked gel formation that could retard
      insulin release and migration into systemic circulation. CONCLUSION:
      Physicochemical responses of additives in vivo affected blood glucose regulation
      property of pectin-insulin nanoparticles.

PMID- 24329401
TI  - Prevalence of restless legs syndrome in female blood donors 1 week after blood
      donation.
AB  - BACKGROUND AND OBJECTIVE: Restless legs syndrome (RLS) is a frequent condition
      with a prevalence of 5-15% in the general population. Clinical and genetic
      observations have shown that iron deficiency, highly prevalent among blood
      donors, can be related to RLS. The objective of this study was to assess the
      prevalence of RLS in female blood donors 1 week after blood donation. METHODS:
      One week after blood donation, 291 female blood donors, aged <50 years, self
      responded to all four RLS questions defined by the 1995 International RLS study
      group. Blood donation rate, fatigue, aerobic capacity, menstruation, mood
      disorder and quality of life were also assessed along with haemoglobin and
      ferritin blood concentrations. RESULTS: Prevalence of RLS in female blood donors
      1 week after blood donation was 6.9% (CI 95% 4.2-10.4%). Female blood donors with
      RLS had a higher prevalence of hyper-menorrhaea (P = 0.033) and were
      significantly more tired (P = 0.001). We observed no associations between RLS and
      number of previous donations (P = 0.409), aerobic capacity (P = 0.476), mood
      disorder (P = 0.169), quality of life (P = 0.356), haemoglobin (P = 0.087), and
      serum ferritin level (P = 0.446). CONCLUSION: Restless legs syndrome prevalence
      in female blood donors is not as important as described in some other studies,
      which could reassure blood donors. The prevalence of hypermenorrhaea and fatigue
      is higher in RLS blood donors. Therefore, screening for fatigue and
      hypermenorrhaea could be considered as these symptoms are associated with RLS in
      female blood donors.

PMID- 24329402
TI  - First study on gene expression of cement proteins and potential adhesion-related
      genes of a membranous-based barnacle as revealed from Next-Generation Sequencing
      technology.
AB  - This is the first study applying Next-Generation Sequencing (NGS) technology to
      survey the kinds, expression location, and pattern of adhesion-related genes in a
      membranous-based barnacle. A total of 77,528,326 and 59,244,468 raw sequence
      reads of total RNA were generated from the prosoma and the basis of Tetraclita
      japonica formosana, respectively. In addition, 55,441 and 67,774 genes were
      further assembled and analyzed. The combined sequence data from both body parts
      generates a total of 79,833 genes of which 47.7% were shared. Homologues of
      barnacle cement proteins - CP-19K, -52K, and -100K - were found and all were
      dominantly expressed at the basis where the cement gland complex is located. This
      is the main area where transcripts of cement proteins and other potential
      adhesion-related genes were detected. The absence of another common barnacle
      cement protein, CP-20K, in the adult transcriptome suggested a possible life
      stage restricted gene function and/or a different mechanism in adhesion between
      membranous-based and calcareous-based barnacles. 

PMID- 24329403
TI  - Triplet-triplet energy transfer from a UV-A absorber butylmethoxydibenzoylmethane
      to UV-B absorbers.
AB  - The phosphorescence decay of a UV-A absorber, 4-tert-butyl-4'
      methoxydibenzolymethane (BMDBM) has been observed following a 355 nm laser
      excitation in the absence and presence of UV-B absorbers, 2-ethylhexyl 4
      methoxycinnamate (octyl methoxycinnamate, OMC) and octocrylene (OCR) in ethanol
      at 77 K. The lifetime of the lowest excited triplet (T1) state of BMDBM is
      significantly reduced in the presence of OMC and OCR. The observed quenching of
      BMDBM triplet by OMC and OCR suggests that the intermolecular triplet-triplet
      energy transfer occurs from BMDBM to OMC and OCR. The T1 state of OCR is
      nonphosphorescent or very weakly phosphorescent. However, we have shown that the
      energy level of the T1 state of OCR is lower than that of the enol form of BMDBM.
      Our methodology of energy-donor phosphorescence decay measurements can be applied
      to the study of the triplet-triplet energy transfer between UV absorbers even if
      the energy acceptor is nonphosphorescent. In addition, the delayed fluorescence
      of BMDBM due to triplet-triplet annihilation was observed in the BMDBM-OMC and
      BMDBM-OCR mixtures in ethanol at 77 K. Delayed fluorescence is one of the
      deactivation processes of the excited states of BMDBM under our experimental
      conditions.

PMID- 24329404
TI  - Dynamics and photochemistry of neutral van der waals clusters.
AB  - This review covers the field of excited electronic-state chemical reactions in
      small clusters. The clusters emphasized are those comprised of an organic
      chromophore that is electronically excited to initiate the reaction and of
      various coreactant molecules ranging from water and ammonia to ethers, amines,
      aromatics, alkanes, alkenes, and diatomics. The reactions discussed include
      vibrational relaxation, vibrational predissociation, electron transfer, proton
      transfer, and radical additions. The reactions are analyzed based on laser
      induced fluorescence excitation, dispersed emission, mass-resolved excitation
      spectroscopy, stimulated emission pumping, and picosecond time-resolved
      implementation of these spectroscopies. 

PMID- 24329405
TI  - Alterations in the CNS effects of anti-epileptic drugs by Chinese herbal
      medicines.
AB  - INTRODUCTION: Concomitant use of anti-epileptic drugs (AEDs) and Chinese herbal
      medicines (CHMs) is increasing globally. However, information summarizing how
      CHMs might alter the CNS effects of AEDs is lacking. AREAS COVERED: A systematic
      review of the English-language articles in evidence-based databases was
      performed. It identified CHMs that interact with AEDs and lead to alterations in
      the CNS effects of AEDs. This review provides a descriptive summary of the
      existing information on CHM-induced changes of both the therapeutic and adverse
      CNS effects of AEDs, including i) anti-epileptic effect, ii) sedative effect,
      iii) anxiolytic effect and iv) memory impairment effect. The proposed mechanisms
      behind the interactions are also summarized. EXPERT OPINION: Despite the
      popularity of both AEDs and CHMs, the availability of information on CHM-AED
      interactions that could result in altered CNS outcomes is considerably limited.
      Moreover, there are some insufficiencies in the study designs of the identified
      reports. More research, including both mechanistic and human studies, with
      improved study design is necessary to ensure the safety and efficacy of
      combinational use of AEDs with CHMs.

PMID- 24329406
TI  - Editorial: evidence in couple and family therapy- the legacy of Alan Gurman.

PMID- 24329407
TI  - The efficacy of systemic therapy for internalizing and other disorders of
      childhood and adolescence: a systematic review of 38 randomized trials.
AB  - Systemic therapy (ST) is one of the most widely applied psychotherapeutic
      approaches in the treatment of children and adolescents, yet few systematic
      reviews exist on the efficacy of ST with this age group. Parallel to a similar
      study on adults, a systematic review was performed to analyze the efficacy of ST
      in the treatment of children and adolescents. All randomized or matched
      controlled trials (RCT) evaluating ST in any setting with child and adolescent
      index patients were identified by database searches and cross-references, as well
      as in existing meta-analyses and reviews. Inclusion criteria were: index patient
      diagnosed with a DSM-IV or ICD-10 listed psychological disorder, or suffering
      from other clinically relevant conditions, and trial published by December 2011.
      Studies were analyzed according to their sample, research methodology,
      interventions applied, and results at end-of-treatment and at follow-up. This
      article presents findings for internalizing and mixed disorders. Thirty-eight
      trials were identified, with 33 showing ST to be efficacious for the treatment of
      internalizing disorders (including mood disorders, eating disorders, and
      psychological factors in somatic illness). There is some evidence for ST being
      also efficacious in mixed disorders, anxiety disorders, Asperger disorder, and in
      cases of child neglect. Results were stable across follow-up periods of up to 5
      years. Trials on the efficacy of ST for externalizing disorders are presented in
      a second article. There is a sound evidence base for the efficacy of ST as a
      treatment for internalizing disorders of child and adolescent patients. 

PMID- 24329408
TI  - A critical methodological review of discourse and conversation analysis studies
      of family therapy.
AB  - Discourse (DA) and conversation (CA) analysis, two qualitative research methods,
      have been recently suggested as potentially promising for the study of family
      therapy due to common epistemological adherences and their potential for an in
      situ study of therapeutic dialog. However, to date, there is no systematic
      methodological review of the few existing DA and CA studies of family therapy.
      This study aims at addressing this lack by critically reviewing published DA and
      CA studies of family therapy on methodological grounds. Twenty-eight articles in
      total are reviewed in relation to certain methodological axes identified in the
      relevant literature. These include choice of method, framing of research
      question(s), data/sampling, type of analysis, epistemological perspective,
      content/type of knowledge claims, and attendance to criteria for good quality
      practice. It is argued that the reviewed studies show "glimpses" of the methods'
      potential for family therapy research despite the identification of certain
      "shortcomings" regarding their methodological rigor. These include unclearly
      framed research questions and the predominance of case study designs. They also
      include inconsistencies between choice of method, stated or unstated
      epistemological orientations and knowledge claims, and limited attendance to
      criteria for good quality practice. In conclusion, it is argued that DA and CA
      can add to the existing quantitative and qualitative methods for family therapy
      research. They can both offer unique ways for a detailed study of the actual
      therapeutic dialog, provided that future attempts strive for a methodologically
      rigorous practice and against their uncritical deployment. 

PMID- 24329409
TI  - Development of a children's version of the SCORE Index of Family Function and
      Change.
AB  - The Systemic Clinical Outcome and Routine Evaluation (SCORE) Index of Family
      Function and Change is a recently developed outcome measure. It was designed to
      be acceptable to adults and children aged 12 and over. Thus far no research has
      been conducted using the SCORE in children under the age of 12. The aim of this
      study was to pilot a children's version of the SCORE. An existing 29-item version
      of the SCORE was completed by a sample of seven children aged 8-10. Time was
      allowed for group discussion with the children. Feedback from this stage of the
      study was used to develop a draft version of the SCORE for children. An expert
      panel of clinicians and researchers were also consulted. A pilot version of the
      Child SCORE was administered to 80 children aged 7-10 in an inner London primary
      school. Thirty-five children also completed the measure for a second time, 1 week
      later. Findings suggested that the Child SCORE was acceptable to children in the
      8-11 age range. Values for internal reliability and test-retest reliability were
      good. The Child SCORE appears to be a promising instrument. Further research is
      required to confirm its acceptability to clinical populations, and to demonstrate
      sensitivity to change. 

PMID- 24329410
TI  - Quality of life, treatment adherence, and locus of control: multiple family
      groups for chronic medical illnesses.
AB  - The Multiple Family Groups (MFGs) approach for patients with a chronic medical
      illness and their families is a structured psychoeducational program that unfolds
      in six weekly 90-minute sessions. In the MFGs, patients and family members
      explore new ways to balance illness and nonillness priorities in family life
      (Steinglass, 1998; Steinglass, 2000 Cuadernos de Terapia Familiar, 44-45, 11;
      Steinglass, Ostroff, & Steinglass, 2011 Family Process, 50, 393). 

PMID- 24329411
TI  - Hope and burden among Latino families of adults with schizophrenia.
AB  - This study examined hope and family burden among Latino families of individuals
      with schizophrenia. The sample consisted of 54 family members, one family member
      per outpatient adult recruited from public mental health programs in a diverse
      urban community. Hierarchical linear regression analyses were used to test the
      hypothesis that the family member's increased hope for the patient's future would
      be associated with decreased family burden beyond effects explained by the
      patient's length of illness and severity of symptoms. Results supported the study
      hypothesis. Family hope for the patient's future was associated with four of five
      types of family burden. Findings point to the prominent role of hope as a source
      of resilience for Latino families dealing with severe mental illness of a loved
      one. 

PMID- 24329412
TI  - Caregiver attributions for late-life depression and their associations with
      caregiver burden.
AB  - Late-life depression (LLD) has detrimental effects on family caregivers that may
      be compounded when caregivers believe that depressive behaviors are volitional or
      within the patient's capacity to control. In this study we examined three person
      centered caregiver attributions that place responsibility for LLD on the patient
      (i.e., character, controllability, and intention), and the impact of such
      attributions on levels of general caregiver burden and burden specific to patient
      depressive symptoms. Participants were 212 spouses and adult children of older
      adults enrolled in a depression treatment study. Over one third of caregivers
      endorsed character attributions, which significantly predicted greater levels of
      both general and depression-specific burden. Intention attributions were
      significantly associated with general burden, but not depression-specific burden.
      Contrary to our expectation, controllability attributions did not predict either
      type of burden. Our findings suggest that the assessment of family caregiver
      attributions for LLD may be useful in identifying caregivers at risk for burden
      and subsequent health effects, as well as those who may need education and
      support to provide effective care to a vulnerable population of older adults. 

PMID- 24329413
TI  - Father-involvement in a refugee sample: relations between posttraumatic stress
      and caregiving.
AB  - Despite increased attention to the role of fathers within families, there is
      still a dearth of studies on the impact of trauma on father-involvement. This
      study investigates the quantity of father-involvement and the influence of
      posttraumatic stress on the quality of involvement in a refugee and asylum seeker
      population. Eighty refugees and asylum seekers and their young children (aged 18
      42 months) were recruited. Measures included assessment of parental trauma
      (Harvard Trauma Questionnaire), quantity and quality of involvement (quantity of
      caregiving and Emotional Availability Scales), and perception of the father-child
      relationship (interview). The results show that fathers were less involved in
      caregiving tasks and play activities than mothers. No parental gender differences
      were found on each of the Emotional Availability Scales. Traumatic stress
      symptoms negatively affected the perception and the actual quality of parent
      child interaction (sensitivity, structuring, nonhostility). Nevertheless, almost
      all fathers described their relationship with their child as good and their child
      as very important to them. As the quality of father-involvement is of importance
      to the development of the child, traumatized fathers are as much in need of
      clinical intervention as mothers. Despite the impact of posttraumatic stress,
      refugee fathers clearly are involved in the lives of their children. Mechanisms
      such as a deliberate withdrawal when stressed and compensation might enable
      affected fathers to step into the interaction when needed, raise the quality of
      involvement with their child, and diminish the negative impact of stress
      resulting from trauma and migration. 

PMID- 24329414
TI  - Identification of REST-regulated genes and pathways using a REST-targeted
      antisense approach.
AB  - The repressor element-1 silencing transcription factor/neuron-restrictive
      silencer factor (REST/NRSF) is one of the first negative-acting transcriptional
      regulators implicated in vertebrate development thought to regulate hundreds of
      neuron-specific genes. However, its function in the adult system remains elusive.
      Here we employ second-generation antisense oligonucleotides (ASOs) to study the
      impact of rest-mediated suppression on gene expression. We demonstrate specific
      reductions in REST levels in vitro, and in vivo in mouse liver following
      treatment with ASOs, and we show that ASO mediated-REST suppression results in
      the elevation in expression of many neuronal genes including brain-derived
      neurotrophic factor, Synapsin1 (syn1) and beta3-tubulin in BALB/c liver.
      Furthermore, we show the elevation of the affected proteins in plasma following
      ASO treatment. Finally, microarray analysis was applied to identify a broad range
      of genes modulated by REST suppression in mouse liver. Our findings suggest that
      REST may be an important target for neurodegenerative diseases like Huntington's
      disease, is also involved in the regulation of a broad range of additional
      cellular pathways, and that the antisense approach is a viable strategy for
      selectively modulating REST activity in vivo.

PMID- 24329415
TI  - 9th annual meeting of the Oligonucleotide Therapeutics Society Naples, Italy |
      October 6-8, 2013. Session summaries.

PMID- 24329416
TI  - Plain radiography is effective for the detection of calcinosis cutis occurring in
      association with autoimmune connective tissue disease.
AB  - BACKGROUND: Studies on the radiological findings of calcinosis cutis in patients
      with autoimmune connective tissue disease (ACTD) are limited. OBJECTIVES: To
      describe imaging findings and radiological patterns of calcinosis cutis occurring
      with ACTD. METHODS: We retrospectively reviewed the cases of 37 patients with
      imaging studies assessing for calcinosis cutis associated with ACTD at our
      institution between 1996 and 2009. A formal blinded review of available images
      (i.e. radiographs, computed tomography scans) for all 37 patients was performed
      by radiologists. RESULTS: Of 37 patients, 30 (81%) were female. The mean age at
      diagnosis of calcinosis cutis was 43.4 years. Patients had the following ACTDs:
      dermatomyositis (n = 17) with classic (n = 9), juvenile (n = 7) and amyopathic (n
      = 1) subtypes; systemic sclerosis with limited cutaneous scleroderma (n = 8);
      undifferentiated connective tissue disease (n = 4); mixed connective tissue
      disease (n = 3); systemic lupus erythematosus (n = 2); lupus panniculitis (n =
      1); overlap connective tissue disease (n = 1); and polymyositis (n = 1). Plain
      radiographs detected calcinosis in all 37 patients; a nodular pattern of
      calcification was most commonly observed (31/37; 84%). Two or more morphological
      patterns of calcification were present in 19 patients (51%). In general,
      individual patterns were not specific to a particular ACTD subtype. CONCLUSIONS:
      Radiography detected calcinosis in all patients and is recommended for initial
      imaging of calcinosis. Multiple morphological patterns of calcification were
      observed across ACTD subtypes. Further studies should correlate radiological
      studies with treatment of calcinosis and underlying ACTD.

PMID- 24329419
TI  - Interferon lambda genetic polymorphisms and viral infection: the tip of the
      iceberg?
AB  - Pathogen-host interaction studies have demonstrated the importance of host
      factors in the pathogenesis of infectious disease. An emerging theme is that
      polymorphisms in the genes encoding these factors can influence the host response
      to infection and the course of disease. Genetic variation affecting interferon
      lambda (IFN-lambda) expression is now known to influence the outcome of both
      hepatitis C virus and herpes simplex virus type 1 infection in humans. IFN-lambda
      is expressed at higher levels in organs with high epithelial cell content such as
      the respiratory and gastrointestinal tracts. Interestingly, data from animal
      models show that IFN-lambda contributes to host control of viruses infecting
      these sites, including influenza A virus, severe acute respiratory syndrome
      coronavirus, and rotavirus. Furthermore, defective IFN-lambda production by
      humans with asthma impairs the control of rhinovirus infection. We hypothesize
      that genetic variation of IFN-lambda could potentially influence the course of
      disease during infection with many viruses that infect epithelial cells. 

PMID- 24329418
TI  - Chronic ethanol consumption modulates growth factor release, mucosal cytokine
      production, and microRNA expression in nonhuman primates.
AB  - BACKGROUND: Chronic alcohol consumption has been associated with enhanced
      susceptibility to both systemic and mucosal infections. However, the exact
      mechanisms underlying this enhanced susceptibility remain incompletely
      understood. METHODS: Using a nonhuman primate model of ethanol (EtOH) self
      administration, we examined the impact of chronic alcohol exposure on immune
      homeostasis, cytokine, and growth factor production in peripheral blood, lung,
      and intestinal mucosa following 12 months of chronic EtOH exposure. RESULTS: EtOH
      exposure inhibited activation-induced production of growth factors hepatocyte
      growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and vascular
      endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMC).
      Moreover, EtOH significantly reduced the frequency of colonic Th1 and Th17 cells
      in a dose-dependent manner. In contrast, we did not observe differences in
      lymphocyte frequency or soluble factor production in the lung of EtOH-consuming
      animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17
      cytokine production, we compared expression levels of microRNAs in PBMC and
      intestinal mucosa. Our analysis revealed EtOH-dependent up-regulation of distinct
      microRNAs in affected tissues (miR-181a and miR-221 in PBMC; miR-155 in colon).
      Moreover, we were able to detect reduced expression of the transcription factors
      STAT3 and ARNT, which regulate expression of VEGF, G-CSF, and HGF and contain
      targets for these microRNAs. To confirm and extend these observations, PBMC were
      transfected with either mimics or antagomirs of miR-181 and miR-221, and protein
      levels of the transcription factors and growth factors were determined.
      Transfection of microRNA mimics led to a reduction in both STAT3/ARNT as well as
      VEGF/HGF/G-CSF levels. The opposite outcome was observed when microRNA antagomirs
      were transfected. CONCLUSIONS: Chronic EtOH consumption significantly disrupts
      both peripheral and mucosal immune homeostasis, and this dysregulation may be
      mediated by changes in microRNA expression.

PMID- 24329420
TI  - Improving the accuracy in prognosis for Burkitt lymphoma patients.
AB  - A recent population-based study on 2000 adult patients with Burkitt lymphoma
      presented a novel score that takes into account age, race and clinical stage to
      prognosticate survival. The outcome of patients with Burkitt lymphoma has
      improved in the last decade, likely due to intensive chemotherapy regimens and
      anti-CD20 monoclonal antibody therapy. There is, however, a lack of improvement
      in the outcome of patients older than 60 and in black patients. In this article,
      we discuss the findings of that study as well as the areas of uncertainty and/or
      disparity in the prognosis of patients with Burkitt lymphoma. 

PMID- 24329421
TI  - Sulfated polysaccharide isolated from Ulva lactuca attenuates d-galactosamine
      induced DNA fragmentation and necrosis during liver damage in rats.
AB  - Abstract Context: Ulva lactuca Linnaeus (Chlorophyceae), a commonly distributed
      seaweed, is rich in polysaccharide but has not been studied extensively.
      Objective: The present study investigated the effects of crude fraction of Ulva
      lactuca polysaccharide (ULP) on d-galactosamine (d-Gal)-induced DNA damage,
      hepatic oxidative stress, and necrosis in rats. Materials and methods: The rats
      were treated with ULP (100 mg/kg, orally) for 4 weeks before a single
      intraperitoneal injection of d-Gal (500 mg/kg). In addition to liver cell
      necrosis and DNA damage, antioxidant parameters, such as lipid peroxide (LPO),
      superoxide dismutase, and catalase, and histopathology of liver tissue were
      evaluated. Results: ULP pre-treatment significantly attenuated a d-Gal-induced
      decrease in DNA and RNA levels (3.67 +/- 0.38) and (5.42 +/- 0.46), respectively.
      Comet tail length and acridine staining confirmed the number of cells undergoing
      necrosis were relatively lower in ULP treated rats (30 um and 8-10% of counted
      cells) compared to rats treated with d-Gal (60 um and 16% of counted cells).
      Biochemical (LPO, SOD and CAT) and histological evaluation (p < 0.01) confirmed
      the anti-hepatotoxic and antioxidant property of crude polysaccharide against d
      Gal-induced elevation of LPO and infiltration of inflammatory cells into liver
      tissue. Discussion and conclusion: Although our previous studies have reported on
      the protective role of ULP against liver toxicity, our present findings show that
      ULP improved the hepatic antioxidant defense system against d-Gal-induced DNA
      damage and necrosis in rats.

PMID- 24329422
TI  - Craft activities in groups at meeting places: supporting mental health users'
      everyday occupations.
AB  - AIM: People with mental health illness often lose everyday occupations that give
      life consistency. Recovery is therefore supposed to take place through
      transactions between person and environment. Such transactions might occur at
      meeting places. These services offer voluntary participation to support
      participants' inclusion in the society, and are part of the Norwegian Mental
      Health reforms. Crafts are one of the activities used at the meeting places.
      There is limited empirical research on the interventions of activities at these
      services. Therefore the aim of this study was to explore how the participants'
      engagements in craft activities in a group supported their way of managing
      everyday occupations. METHODS: Ethnography was chosen as a design, to meet the
      study's exploratory aim. The participants in the study were 12 people with long
      lasting mental health illness. RESULTS: Procedures for paradigmatic analysis were
      followed, and brought forward three themes: doing crafts in a group facilitated
      stability and routines, skills and abilities, and peer support. The discussion
      reflected knowledge and experiences of crafts as an activity with a low-risk
      threshold for participation and its healing value. How the doing of craft
      activities in a group offered transactional space to gain experiences to manage
      everyday occupations was further discussed.

PMID- 24329424
TI  - Feasibility and acceptability of a collaborative care intervention to improve
      symptoms and quality of life in chronic heart failure: mixed methods pilot trial.
AB  - BACKGROUND: People with chronic heart failure (HF) suffer from numerous symptoms
      that worsen quality of life. The CASA (Collaborative Care to Alleviate Symptoms
      and Adjust to Illness) intervention was designed to improve symptoms and quality
      of life by integrating palliative and psychosocial care into chronic care.
      OBJECTIVE: Our aim was to determine the feasibility and acceptability of CASA and
      identify necessary improvements. METHODS: We conducted a prospective mixed
      methods pilot trial. The CASA intervention included (1) nurse phone visits
      involving structured symptom assessments and guidelines to alleviate
      breathlessness, fatigue, pain, or depression; (2) structured phone counseling
      targeting adjustment to illness and depression if present; and (3) weekly team
      meetings with a palliative care specialist, cardiologist, and primary care
      physician focused on medical recommendations to primary care providers (PCPs,
      physician or nurse practioners) to improve symptoms. Study subjects were
      outpatients with chronic HF from a Veteran's Affairs hospital (n=15) and a
      university hospital (n=2). Measurements included feasibility (cohort retention
      rate, medical recommendation implementation rate, missing data, quality of care)
      and acceptability (an end-of-study semi-structured participant interview).
      RESULTS: Participants were male with a median age of 63 years. One withdrew early
      and there were <5% missing data. Overall, 85% of 87 collaborative care team
      medical recommendations were implemented. All participants who screened positive
      for depression were either treated for depression or thought to not have a
      depressive disorder. In the qualitative interviews, patients reported a positive
      experience and provided several constructive critiques. CONCLUSIONS: The CASA
      intervention was feasible based on participant enrollment, cohort retention,
      implementation of medical recommendations, minimal missing data, and
      acceptability. Several intervention changes were made based on participant
      feedback.

PMID- 24329425
TI  - High-efficiency broadband meta-hologram with polarization-controlled dual images.
AB  - Holograms, the optical devices to reconstruct predesigned images, show many
      applications in our daily life. However, applications of hologram are still
      limited by the constituent materials and therefore their working range is trapped
      at a particular electromagnetic region. In recent years, the metasurfaces, an
      array of subwavelength antenna with varying sizes, show the abilities to
      manipulate the phase of incident electromagnetic wave from visible to microwave
      frequencies. Here, we present a reflective-type and high-efficiency meta-hologram
      fabricated by metasurface for visible wavelength. Using gold cross nanoantennas
      as building blocks to construct our meta-hologram devices with thickness ~
      lambda/4, the reconstructed images of meta-hologram show polarization-controlled
      dual images with high contrast, functioning for both coherent and incoherent
      light sources within a broad spectral range and under a wide range of incidence
      angles. The flexibility demonstrated here for our meta-hologram paves the road to
      a wide range of applications related to holographic images at arbitrary
      electromagnetic wave region. 

PMID- 24329426
TI  - Enhancing the thermal stability of Majorana fermions with redundancy using
      dipoles in optical lattices.
AB  - Pairing between spinless fermions can generate Majorana fermion excitations that
      exhibit intriguing properties arising from nonlocal correlations. But, simple
      models indicate that nonlocal correlation between Majorana fermions becomes
      unstable at nonzero temperatures. We address this issue by showing that
      anisotropic interactions between dipolar fermions in optical lattices can be used
      to significantly enhance thermal stability. We construct a model of oriented
      dipolar fermions in a square optical lattice. We find that domains established by
      strong interactions exhibit enhanced correlation between Majorana fermions over
      large distances and long times even at finite temperatures, suitable for stable
      redundancy encoding of quantum information. Our approach can be generalized to a
      variety of configurations and other systems, such as quantum wire arrays. 

PMID- 24329427
TI  - Topological entanglement entropy with a twist.
AB  - Defects in topologically ordered models have interesting properties that are
      reminiscent of the anyonic excitations of the models themselves. For example,
      dislocations in the toric code model are known as twists and possess properties
      that are analogous to Ising anyons. We strengthen this analogy by using the
      topological entanglement entropy as a diagnostic tool to identify properties of
      both defects and excitations in the toric code. Specifically, we show, through
      explicit calculation, that the toric code model including twists and dyon
      excitations has the same quantum dimensions, the same total quantum dimension,
      and the same fusion rules as an Ising anyon model. 

PMID- 24329428
TI  - Observation of surface states with algebraic localization.
AB  - We introduce and experimentally demonstrate a class of surface bound states with
      algebraic decay in a one-dimensional tight-binding lattice. Such states have an
      energy embedded in the spectrum of scattered states and are structurally stable
      against perturbations of lattice parameters. Experimental demonstration of
      surface states with algebraic localization is presented in an array of
      evanescently coupled optical waveguides with tailored coupling rates. 

PMID- 24329429
TI  - What does one measure when one measures the arrival time of a quantum particle?
AB  - What is the right statistics for the measurements of arrival times of a quantum
      particle? Although this question is very old, it is still open. The usual
      experiments are performed in the far-field regime and this question becomes
      unimportant, as a semiclassical analysis suffices. Nevertheless, the development
      in the detector technology will soon allow for near-field investigations; thus, a
      better understanding of arrival time measurements is needed. Since outcomes of
      quantum measurements are always described by positive-operator-valued measures
      (POVMs), various arrival time POVMs have been proposed. On the other hand, many
      physicists would agree that the arrival time statistics is given by the quantum
      flux. This urges the question whether a POVM exists, which agrees approximately
      with the quantum flux values on a reasonable set of wave functions. We answer
      this question negatively for a very natural set of wave functions, but we remark
      that the answer is very sensitive to the choice of the set and provide evidence
      for the existence of a POVM that agrees with the quantum flux on a more
      restrictive set. 

PMID- 24329430
TI  - Impurity problem in a bilayer system of dipoles.
AB  - We consider a bilayer geometry where a single impurity moves in a two-dimensional
      plane and is coupled, via dipolar interactions, to a two-dimensional system of
      fermions residing in the second layer. Dipoles in both layers point in the same
      direction oriented by an external field perpendicular to the plane of motion. We
      use quantum Monte Carlo methods to calculate the binding energy and the effective
      mass of the impurity at zero temperature as a function of the distance between
      layers as well as of the in-plane interaction strength. In the regime where the
      fermionic dipoles form a Wigner crystal, the physics of the impurity can be
      described in terms of a polaron coupled to the bath of lattice phonons. By
      reducing the distance between layers this polaron exhibits a crossover from a
      free-moving to a tightly bound regime where its effective mass is orders of
      magnitude larger than the bare mass.

PMID- 24329431
TI  - Geometric phase effects in dynamics near conical intersections: symmetry breaking
      and spatial localization.
AB  - We show that finite systems with conical intersections can exhibit spontaneous
      symmetry breaking which manifests itself in spatial localization of eigenstates.
      This localization has a geometric phase origin and is robust against variation of
      model parameters. The transition between localized and delocalized eigenstate
      regimes resembles a continuous phase transition. The localization slows down the
      low-energy quantum nuclear dynamics at low temperatures. 

PMID- 24329432
TI  - Effects of Berry curvature on the collective modes of ultracold gases.
AB  - Topological energy bands have important geometrical properties described by the
      Berry curvature. We show that the Berry curvature changes the hydrodynamic
      equations of motion for a trapped Bose-Einstein condensate, and causes
      significant modifications to the collective mode frequencies. We illustrate our
      results for the case of two-dimensional Rashba spin-orbit coupling in a Zeeman
      field. Using an operator approach, we derive the effects of Berry curvature on
      the dipole mode in very general settings. We show that the sizes of these effects
      can be large and readily detected in experiment. Collective modes therefore
      provide a sensitive way to measure geometrical properties of energy bands. 

PMID- 24329433
TI  - Cavity-mediated near-critical dissipative dynamics of a driven condensate.
AB  - We investigate the near-critical dynamics of atomic density fluctuations in the
      nonequilibrium self-organization transition of an optically driven quantum gas
      coupled to a single mode of a cavity. In this system cavity-mediated long-range
      interactions between atoms, tunable by the drive strength, lead to softening of
      an excitation mode recently observed in experiments. This phenomenon has
      previously been studied within a two-mode approximation for the collective
      motional degrees of freedom of the atomic condensate, which results in an
      effective open-system Dicke model. Here, including the full spectrum of atomic
      modes we find a finite lifetime for a rotonlike mode in the Bogoliubov excitation
      spectrum that is strongly pump dependent. The corresponding decay rate and
      critical exponents for the phase transition are calculated explaining the
      nonmonotonic pump-dependent atomic damping rate observed in recent experiments.
      We compute the near-critical behavior of the intracavity field fluctuations that
      has been previously shown to be enhanced with respect to the equilibrium Dicke
      model in a two-mode approximation. We highlight the role of the finite size of
      the system in the suppression of it below the expectations of the open Dicke
      model. 

PMID- 24329434
TI  - Experimental detection of quantum channels.
AB  - We demonstrate experimentally the possibility of efficiently detecting properties
      of quantum channels and quantum gates. The experimentally realized quantum
      channel detection method has been recently proposed theoretically, and allows us
      to characterize the properties of quantum channels with a much smaller
      experimental effort than quantum process tomography. Here, the optimal detection
      scheme is first achieved for nonentanglement breaking channels of the
      depolarizing form and is based on the generation and detection of polarized
      entangled photons. We then demonstrate channel detection for nonseparable maps by
      considering the CNOT gate and employing two-photon hyperentangled states. 

PMID- 24329435
TI  - Localization of negative energy and the Bekenstein bound.
AB  - A simple argument shows that negative energy cannot be isolated far away from
      positive energy in a conformal field theory and strongly constrains its possible
      dispersal. This is also required by consistency with the Bekenstein bound written
      in terms of the positivity of relative entropy. We prove a new form of the
      Bekenstein bound based on the monotonicity of the relative entropy, involving a
      "free" entropy enclosed in a region which is highly insensitive to space-time
      entanglement, and show that it further improves the negative energy localization
      bound. 

PMID- 24329436
TI  - Phenomenological characterization of semiholographic non-Fermi liquids.
AB  - We analyze some phenomenological implications of the most general semiholographic
      models for non-Fermi liquids that have emerged with inputs from the holographic
      correspondence. We find generalizations of Landau-Silin equations with few
      parameters governing thermodynamics, low-energy response, and collective
      excitations. We show that even when there is a Fermi surface with well-defined
      quasiparticle excitations, the collective excitations can behave very differently
      from Landau's theory. 

PMID- 24329438
TI  - Impact of nuclear effects on the extraction of neutrino oscillation parameters.
AB  - study the possible impact of nuclear effects and final state interactions on the
      determination of the oscillation parameters due to the misreconstruction of
      nonquasielastic events as quasielastic events at low energies. We analyze a
      nu(MU) disappearance experiment using a water Cerenkov detector. We find that, if
      completely ignored in the fit, nuclear effects can induce a significant bias in
      the determination of atmospheric oscillation parameters, particularly for the
      atmospheric mixing angle. Even after inclusion of a near detector, a bias in the
      determination of the atmospheric mixing angle comparable to the statistical error
      remains.

PMID- 24329439
TI  - Searching for light dark matter with the SLAC millicharge experiment.
AB  - New sub-GeV gauge forces ("dark photons") that kinetically mix with the photon
      provide a promising scenario for MeV-GeV dark matter and are the subject of a
      program of searches at fixed-target and collider facilities around the world. In
      such models, dark photons produced in collisions may decay invisibly into dark
      matter states, thereby evading current searches. We reexamine results of the SLAC
      mQ electron beam dump experiment designed to search for millicharged particles
      and find that it was strongly sensitive to any secondary beam of dark matter
      produced by electron-nucleus collisions in the target. The constraints are
      competitive for dark photon masses in the ~1-30 MeV range, covering part of the
      parameter space that can reconcile the apparent (g-2)(MU) anomaly. Simple
      adjustments to the original SLAC search for millicharges may extend sensitivity
      to cover a sizable portion of the remaining (g-2)(MU) anomaly-motivated region.
      The mQ sensitivity is therefore complementary to ongoing searches for visible
      decays of dark photons. Compared to existing direct-detection searches, mQ
      sensitivity to electron-dark-matter scattering cross sections is more than an
      order of magnitude better for a significant range of masses and couplings in
      simple models.

PMID- 24329440
TI  - Constraints on new physics from baryogenesis and Large Hadron Collider data.
AB  - We demonstrate the power of constraining theories of new physics by insisting
      that they lead to electroweak baryogenesis, while agreeing with current data from
      the Large Hadron Collider. The general approach is illustrated with a singlet
      scalar extension of the standard model. Stringent bounds can already be obtained,
      which reduce the viable parameter space to a small island. 

PMID- 24329441
TI  - D*(s0)(2317) meson and D-meson-kaon scattering from lattice QCD.
AB  - The scalar meson D*(s0)(2317) is found 37(17) MeV below the DK threshold in a
      lattice simulation of the J(P)=0(+) channel using, for the first time, both DK as
      well as s-c interpolating fields. The simulation is done on N(f)=2+1 gauge
      configurations with m(pi) is approximately equal to 156 MeV, and the resulting
      M(D*(s0))-1/4(M(D(s))+3M(D*(s)))=266(16) MeV is close to the experimental value
      241.5(0.8) MeV. The energy level related to the scalar meson is accompanied by
      additional discrete levels due to DK scattering states. The levels near threshold
      lead to the negative DK scattering length a(0)=-1.33(20) fm that indicates the
      presence of a state below threshold.

PMID- 24329442
TI  - Precise QCD predictions for the production of a photon pair in association with
      two jets.
AB  - We compute the cross section for the production of a high-mass photon pair in
      association with two hadronic jets to next-to-leading order in quantum
      chromodynamics. Our results allow us for the first time to reliably predict the
      absolute normalization of this process and demonstrate that the shape of
      important kinematical distributions is modified by higher-order effects. The
      perturbative corrections will be an important ingredient in precision studies of
      Higgs boson properties from its production in association with two jets. 

PMID- 24329444
TI  - Fully dynamical simulation of central nuclear collisions.
AB  - We present a fully dynamical simulation of central nuclear collisions around
      midrapidity at LHC energies. Unlike previous treatments, we simulate all phases
      of the collision, including the equilibration of the system. For the simulation,
      we use numerical relativity solutions to anti-de Sitter space/conformal field
      theory for the preequilibrium stage, viscous hydrodynamics for the plasma
      equilibrium stage, and kinetic theory for the low-density hadronic stage. Our
      preequilibrium stage provides initial conditions for hydrodynamics, resulting in
      sizable radial flow. The resulting light particle spectra reproduce the
      measurements from the ALICE experiment at all transverse momenta.

PMID- 24329445
TI  - Improved determination of the neutron lifetime.
AB  - The most precise determination of the neutron lifetime using the beam method was
      completed in 2005 and reported a result of tau(n)=(886.3+/-1.2[stat]+/-3.2[syst])
      s. The dominant uncertainties were attributed to the absolute determination of
      the fluence of the neutron beam (2.7 s). The fluence was measured with a neutron
      monitor that counted the neutron-induced charged particles from absorption in a
      thin, well-characterized 6Li deposit. The detection efficiency of the monitor was
      calculated from the areal density of the deposit, the detector solid angle, and
      the evaluated nuclear data file, ENDF/B-VI 6Li(n,t)4He thermal neutron cross
      section. In the current work, we measure the detection efficiency of the same
      monitor used in the neutron lifetime measurement with a second, totally absorbing
      neutron detector. This direct approach does not rely on the 6Li(n,t)4He cross
      section or any other nuclear data. The detection efficiency is consistent with
      the value used in 2005 but is measured with a precision of 0.057%, which
      represents a fivefold improvement in the uncertainty. We verify the temporal
      stability of the neutron monitor through ancillary measurements, allowing us to
      apply the measured neutron monitor efficiency to the lifetime result from the
      2005 experiment. The updated lifetime is tau(n)=(887.7+/-1.2[stat]+/-1.9[syst])
      s.

PMID- 24329446
TI  - Spatial domain interactions between ultraweak optical beams.
AB  - We have observed spatial interactions between two ultraweak optical beams that
      are initially collinear and nonoverlapping. The weak beams are steered towards
      each other by a spatially varying cross-Kerr refractive index waveguide written
      by a strong laser beam in a three-level coherently prepared atomic medium. After
      fusing together, the combined beam shows controllable phase-dependent behaviors.
      This is the first observation of solitonlike interactions between weak beams and
      can be useful for all-optically tunable beam combining, switching, and gating for
      weak photonic signals. 

PMID- 24329447
TI  - Analytic properties of two-photon scattering matrix in integrated quantum systems
      determined by the cluster decomposition principle.
AB  - We consider a general class of integrated quantum systems where photon-photon
      interaction occurs in a quantum device that is localized in space. Using
      techniques that are closely related to cluster decomposition principles in
      quantum field theory, we provide a general constraint on the analytic properties
      of a two-photon S matrix in this class of systems. We also show that the photon
      photon interaction in these systems inevitably leads to frequency mixing and
      entanglement and that frequencies of the single photons cannot be preserved in
      these systems. 

PMID- 24329448
TI  - Goos-Hanchen shifts of partially coherent light fields.
AB  - The Goos-Hanchen (GH) shift refers to a lateral displacement (from the path
      expected from geometrical optics) along an interface in totally internal
      reflection. This phenomenon results from a coherence effect. In order to bring to
      light the role of coherence, the reflection of partially coherent light fields
      was investigated within the framework of the theory of coherence. A formal
      expression for the GH shifts of partially coherent light fields is obtained in
      terms of Mercer's expansion. It is shown that both the spatial coherence and the
      beam width have an important effect on the GH shift, especially near the critical
      angles (such as totally reflection angle). These results are important to observe
      the GH shifts of the beams with imperfect coherence, like x-ray and matter-wave
      beams. 

PMID- 24329449
TI  - Clash of kinks: phase shifts in colliding nonintegrable solitons.
AB  - We derive a closed-form expression for the phase shift experienced by (1+1)
      dimensional kinks colliding at ultrarelativistic velocities (gammav>>1), valid
      for arbitrary periodic potentials. Our closed-form expression is the leading
      order result of a more general scattering theory of solitary waves described in a
      related paper [Phys. Rev. D 88, 105024 (2013)]. This theory relies on a small
      kinematic parameter 1/(gammav)<<1 rather than a small parameter in the
      Lagrangian. Our analytic results can be directly extracted from the Lagrangian
      without solving the equation of motion. Based on our closed-form expression, we
      prove that kink-kink and kink-antikink collisions have identical phase shifts at
      leading order.

PMID- 24329450
TI  - Femtosecond 240-keV electron pulses from direct laser acceleration in a low
      density gas.
AB  - We propose a simple laser-driven electron acceleration scheme based on tightly
      focused radially polarized laser pulses for the production of femtosecond
      electron bunches with energies in the few-hundreds-of-keV range. In this method,
      the electrons are accelerated forward in the focal volume by the longitudinal
      electric field component of the laser pulse. Three-dimensional test-particle and
      particle-in-cell simulations reveal the feasibility of generating well-collimated
      electron bunches with an energy spread of 5% and a temporal duration of the order
      of 1 fs. These results offer a route towards unprecedented time resolution in
      ultrafast electron diffraction experiments.

PMID- 24329451
TI  - Strongly reduced penetration of atomic deuterium in radiation-damaged tungsten.
AB  - Radiation-damaged tungsten is exposed to high-flux, low-energy deuterium plasmas
      at self-bias conditions. We observe that the fraction of deuterium that
      penetrates is only 10(-5)-10(-7) of the plasma flux and strongly dependent on the
      local surface temperature. We propose that deuterium does not directly penetrate
      bulk tungsten but that it thermalizes at the surface, where it forms a protective
      chemisorbed layer. We find an energy barrier of 1-2 eV between the surface and
      bulk, causing the influx of deuterium to be low as compared to the number of
      defects and leading to slow filling of the damaged layer.

PMID- 24329452
TI  - Filamentation instability of counterstreaming laser-driven plasmas.
AB  - Filamentation due to the growth of a Weibel-type instability was observed in the
      interaction of a pair of counterstreaming, ablatively driven plasma flows, in a
      supersonic, collisionless regime relevant to astrophysical collisionless shocks.
      The flows were created by irradiating a pair of opposing plastic (CH) foils with
      1.8 kJ, 2-ns laser pulses on the OMEGA EP Laser System. Ultrafast laser-driven
      proton radiography was used to image the Weibel-generated electromagnetic fields.
      The experimental observations are in good agreement with the analytical theory of
      the Weibel instability and with particle-in-cell simulations.

PMID- 24329454
TI  - Liquid phase stability under an extreme temperature gradient.
AB  - Using nonequilibrium molecular dynamics simulations, we subject bulk liquid to a
      very high-temperature gradient and observe a stable liquid phase with a local
      temperature well above the boiling point. Also, under this high-temperature
      gradient, the vapor phase exhibits condensation into a liquid at a temperature
      higher than the saturation temperature, indicating that the observed liquid
      stability is not caused by nucleation barrier kinetics. We show that, assuming
      local thermal equilibrium, the phase change can be understood from the
      thermodynamic analysis. The observed elevation of the boiling point is associated
      with the interplay between the "bulk" driving force for the phase change and
      surface tension of the liquid-vapor interface that suppresses the transformation.
      This phenomenon is analogous to that observed for liquids in confined geometries.
      In our study, however, a low-temperature liquid, rather than a solid, confines
      the high-temperature liquid. 

PMID- 24329453
TI  - Spin-orbit coupling and quantum spin Hall effect for neutral atoms without spin
      flips.
AB  - We propose a scheme which realizes spin-orbit coupling and the quantum spin Hall
      effect for neutral atoms in optical lattices without relying on near resonant
      laser light to couple different spin states. The spin-orbit coupling is created
      by modifying the motion of atoms in a spin-dependent way by laser recoil. The
      spin selectivity is provided by Zeeman shifts created with a magnetic field
      gradient. Alternatively, a quantum spin Hall Hamiltonian can be created by all
      optical means using a period-tripling, spin-dependent superlattice. 

PMID- 24329455
TI  - Cooperativity and the freezing of molecular motion at the glass transition.
AB  - The slowing down of molecular dynamics when approaching the glass transition
      generally proceeds much stronger than expected for thermally activated motions.
      This strange phenomenon can be formally ascribed to a temperature-dependent
      activation energy E(T). In the present work, via measurements of the third-order
      nonlinear dielectric susceptibility, we deduce the increase of the number of
      correlated molecules N(corr) when approaching the glass transition and find a
      surprisingly simple correlation of E(T) and N(corr)(T). This provides strong
      evidence that the noncanonical temperature development of glassy dynamics is
      caused by a temperature-dependent energy barrier arising from the cooperative
      motion of ever larger numbers of molecules at low temperatures.

PMID- 24329456
TI  - High pressure as a key factor to identify the conductivity mechanism in protic
      ionic liquids.
AB  - In this Letter we report the relation between ionic conductivity and structural
      relaxation in supercooled protic ionic liquids (PILs) under high pressure. The
      results of high-pressure dielectric and volumetric measurements, combined with
      rheological and temperature-modulated differential scanning calorimetry
      experiments, have revealed a fundamental difference between the conducting
      properties under isothermal and isobaric conditions for three PILs with different
      charge transport mechanisms (Grotthuss vs vehicle). Our findings indicate a
      breakdown of the fractional Stokes-Einstein relation and Walden rule when the
      ionic transport is controlled by fast proton hopping. Consequently, we
      demonstrate that the studied PILs exhibit significantly higher conductivity than
      one would expect taking into account that they are in fact a mixture of ionic and
      neutral species. Thus, the examined herein samples represent a new class of
      "superionic" materials desired for many advanced applications. 

PMID- 24329457
TI  - Thermal Boundary Resistance between GaN and Cubic Ice and THz Acoustic
      Attenuation Spectrum of Cubic Ice from Complex Acoustic Impedance Measurements.
AB  - A phonon nanoscopy method, based on the picosecond ultrasonics technique, capable
      of studying the complex acoustic reflection coefficient at frequency up to 1 THz
      is proposed and demonstrated. By measuring the reflection coefficient at the same
      surface location at the interface between GaN and air, and between GaN and the
      material to characterize, we get access to the THz amplitude and phase spectra of
      the acoustic phonon reflection. The retrieval of both these pieces of information
      then allows the calculation of the attenuation in a wide range of frequency and
      gives new insight into the Kapitza anomaly. This method is then applied to cubic
      ice, and the measurements of the elastic properties, the phonon anharmonic decay
      spectrum up to 1 THz, as well as the measurements of the thermal phonon lifetime
      at 150 K are all achieved.

PMID- 24329458
TI  - Wetting transition in water.
AB  - Optical images were used to study the wetting behavior of water on graphite,
      sapphire, and quartz along the liquid vapor coexistence curve from room
      temperature to 300  degrees C. Wetting transitions were identified by the
      temperature at which the contact angle decreased to zero and also by the
      disappearance of dropwise condensation. These two methods yielded consistent
      values for the wetting temperatures, which were 185  degrees C, 234  degrees C,
      and 271  degrees C for water on quartz, sapphire, and graphite, respectively. We
      compare our results with the theoretical predictions based on a simplified model
      of the water-substrate potential and sharp interfaces.

PMID- 24329459
TI  - Force of adhesion upon loss of contact angle hysteresis: when a liquid behaves
      like a solid.
AB  - The theoretically predicted vanishment of the macroscopic contact angle
      hysteresis is found experimentally along with a small but finite force of
      adhesion (F(Ad)~-0.5 MUN) that, unexpectedly, is independent of the history of
      the preload. Our results agree with the prediction of a model in which the
      surface tension of the liquid provides the counterpart of the restoring force of
      an elastic solid, evidencing that the dewetting of a liquid in the absence of
      strong pinning points is equivalent to the detachment of an elastic solid.

PMID- 24329460
TI  - Four-dimensional quantum Hall effect in a two-dimensional quasicrystal.
AB  - One-dimensional (1D) quasicrystals exhibit physical phenomena associated with the
      2D integer quantum Hall effect. Here, we transcend dimensions and show that a
      previously inaccessible phase of matter-the 4D integer quantum Hall effect-can be
      incorporated in a 2D quasicrystal. Correspondingly, our 2D model has a quantized
      charge-pump accommodated by an elaborate edge phenomena with protected level
      crossings. We propose experiments to observe these 4D phenomena, and generalize
      our results to a plethora of topologically equivalent quasicrystals. Thus, 2D
      quasicrystals may pave the way to the experimental study of 4D physics. 

PMID- 24329461
TI  - Algebra of Majorana doubling.
AB  - Motivated by the problem of identifying Majorana mode operators at junctions, we
      analyze a basic algebraic structure leading to a doubled spectrum. For general
      (nonlinear) interactions the emergent mode creation operator is highly nonlinear
      in the original effective mode operators, and therefore also in the underlying
      electron creation and destruction operators. This phenomenon could open up new
      possibilities for controlled dynamical manipulation of the modes. We briefly
      compare and contrast related issues in the Pfaffian quantum Hall state. 

PMID- 24329462
TI  - Cubic topological Kondo insulators.
AB  - Current theories of Kondo insulators employ the interaction of conduction
      electrons with localized Kramers doublets originating from a tetragonal
      crystalline environment, yet all Kondo insulators are cubic. Here we develop a
      theory of cubic topological Kondo insulators involving the interaction of
      Gamma(8) spin quartets with a conduction sea. The spin quartets greatly increase
      the potential for strong topological insulators, entirely eliminating the weak
      topological phases from the diagram. We show that the relevant topological
      behavior in cubic Kondo insulators can only reside at the lower symmetry X or M
      points in the Brillouin zone, leading to three Dirac cones with heavy
      quasiparticles.

PMID- 24329463
TI  - Cooper pairs spintronics in triplet spin valves.
AB  - We study a spin valve with a triplet superconductor spacer intercalated between
      two ferromagnets with noncollinear magnetizations. We show that the
      magnetoresistance of the triplet spin valve depends on the relative orientations
      of the d vector, characterizing the superconducting order parameter, and the
      magnetization directions of the ferromagnetic layers. For devices characterized
      by a long superconductor, the effects of a polarized current sustained by Cooper
      pairs only are observed. In this regime, a supermagnetoresistance effect emerges,
      and the chiral symmetry of the order parameter of the superconducting spacer is
      easily recognized. Our findings open new perspectives in designing spintronics
      devices based on the cooperation of ferromagnetic and triplet correlations. 

PMID- 24329464
TI  - Space-charge transfer in hybrid inorganic-organic systems.
AB  - We discuss density functional theory calculations of hybrid inorganic-organic
      systems that explicitly include the global effects of doping (i.e., position of
      the Fermi level) and the formation of a space-charge layer. For the example of
      tetrafluoro-tetracyanoquinodimethane on the ZnO(0001[over -]) surface we show
      that the adsorption energy and electron transfer depend strongly on the ZnO
      doping. The associated work function changes are large, for which the formation
      of space-charge layers is the main driving force. The prominent doping effects
      are expected to be quite general for charge-transfer interfaces in hybrid
      inorganic-organic systems and important for device design. 

PMID- 24329465
TI  - Measurement of unique magnetic and superconducting phases in oxygen-doped high
      temperature superconductors La(2-x)Sr(x)CuO(4+y).
AB  - We present a combined magnetic neutron scattering and muon spin rotation study of
      the nature of the magnetic and superconducting phases in electronically phase
      separated La(2-x)Sr(x)CuO(4+y), x=0.04, 0.065, 0.09. For all samples, we find
      long-range modulated magnetic order below T(N) is approximately equal to Tc=39 K.
      In sharp contrast to oxygen-stoichiometric La(2-x)Sr(x)CuO(4), we find that the
      magnetic propagation vector as well as the ordered magnetic moment is independent
      of Sr content and consistent with that of the "striped" cuprates. Our study
      provides direct proof that superoxygenation in La(2-x)Sr(x)CuO(4+y) allows the
      spin stripe ordered phase to emerge and phase separate from superconducting
      regions with the hallmarks of optimally doped oxygen-stoichiometric La(2
      x)Sr(x)CuO(4).

PMID- 24329466
TI  - Inelastic neutron scattering study of a nonmagnetic collapsed tetragonal phase in
      nonsuperconducting CaFe2As2: evidence of the impact of spin fluctuations on
      superconductivity in the iron-arsenide compounds.
AB  - The relationship between antiferromagnetic spin fluctuations and
      superconductivity has become a central topic of research in studies of
      superconductivity in the iron pnictides. We present unambiguous evidence of the
      absence of magnetic fluctuations in the nonsuperconducting collapsed tetragonal
      phase of CaFe2As2 via inelastic neutron scattering time-of-flight data, which is
      consistent with the view that spin fluctuations are a necessary ingredient for
      unconventional superconductivity in the iron pnictides. We demonstrate that the
      collapsed tetragonal phase of CaFe2As2 is nonmagnetic, and discuss this result in
      light of recent reports of high-temperature superconductivity in the collapsed
      tetragonal phase of closely related compounds.

PMID- 24329467
TI  - Electric field control of terahertz polarization in a multiferroic manganite with
      electromagnons.
AB  - All-electrical control of a dynamic magnetoelectric effect is demonstrated in a
      classical multiferroic manganite DyMnO3, a material containing coupled
      antiferromagnetic and ferroelectric orders. Because of intrinsic magnetoelectric
      coupling with electromagnons a linearly polarized terahertz light rotates upon
      passing through the sample. The amplitude and the direction of the polarization
      rotation are defined by the orientation of ferroelectric domains and can be
      switched by static voltage. These experiments allow the terahertz polarization to
      be tuned using the dynamic magnetoelectric effect.

PMID- 24329468
TI  - BZT: A Soft Pseudospin Glass.
AB  - In an attempt to understand the origin of relaxor ferroelectricity, it is shown
      that interesting behavior of the onset of nonergodicity and of precursor
      nanodomains, found in first-principles simulations of the relaxor alloy Ba(Zr(1
      x)Ti(x))O(3), can easily be understood within a simple mapping to a soft
      pseudospin glass.

PMID- 24329469
TI  - Mechanical spin control of nitrogen-vacancy centers in diamond.
AB  - We demonstrate direct coupling between phonons and diamond nitrogen-vacancy (NV)
      center spins by driving spin transitions with mechanically generated harmonic
      strain at room temperature. The amplitude of the mechanically driven spin signal
      varies with the spatial periodicity of the stress standing wave within the
      diamond substrate, verifying that we drive NV center spins mechanically. These
      spin-phonon interactions could offer a route to quantum spin control of
      magnetically forbidden transitions, which would enhance NV-based quantum
      metrology, grant access to direct transitions between all of the spin-1 quantum
      states of the NV center, and provide a platform to study spin-phonon interactions
      at the level of a few interacting spins. 

PMID- 24329470
TI  - Nematic-field-driven positioning of particles in liquid crystal droplets.
AB  - Common nematic oils, such as 5CB, experience planar anchoring at aqueous
      interfaces. When these oils are emulsified, this anchoring preference and the
      resulting topological constraints lead to the formation of droplets that exhibit
      one or two point defects within the nematic phase. Here, we explore the
      interactions of adsorbed particles at the aqueous interface through a combination
      of experiments and coarse-grained modeling, and demonstrate that surface-active
      particles, driven by elastic forces in the droplet, readily localize to these
      defect regions in a programmable manner. When droplets include two nanoparticles,
      these preferentially segregate to the two poles, thereby forming highly regular
      dipolar structures that could serve for hierarchical assembly of functional
      structures. Addition of sufficient concentrations of surfactant changes the
      interior morphology of the droplet, but pins defects to the interface, resulting
      in aggregation of the two particles. 

PMID- 24329471
TI  - Collective stop-and-go dynamics of active bacteria swarms.
AB  - We set up a macroscopic model of bacterial growth and transport based on a
      dynamic preferred direction-the collective velocity of the bacteria. This
      collective velocity is subject to the isotropic-nematic transition modeling the
      density-controlled transformation between immotile and motile bacterial states.
      The choice of the dynamic preferred direction introduces a distinctive coupling
      of orientational ordering and transport not encountered otherwise. The approach
      can also be applied to other systems spontaneously switching between individual
      (disordered) and collective (ordered) behavior and/or collectively responding to
      density variations, e.g., bird flocks, fish schools, etc. We observe a
      characteristic and robust stop-and-go behavior. The inclusion of chirality
      results in a complex pulsating dynamics. 

PMID- 24329472
TI  - Amoeboid swimming: a generic self-propulsion of cells in fluids by means of
      membrane deformations.
AB  - Microorganisms, such as bacteria, algae, or spermatozoa, are able to propel
      themselves forward thanks to flagella or cilia activity. By contrast, other
      organisms employ pronounced changes of the membrane shape to achieve propulsion,
      a prototypical example being the Eutreptiella gymnastica. Cells of the immune
      system as well as dictyostelium amoebas, traditionally believed to crawl on a
      substratum, can also swim in a similar way. We develop a model for these
      organisms: the swimmer is mimicked by a closed incompressible membrane with force
      density distribution (with zero total force and torque). It is shown that fast
      propulsion can be achieved with adequate shape adaptations. This swimming is
      found to consist of an entangled pusher-puller state. The autopropulsion distance
      over one cycle is a universal linear function of a simple geometrical
      dimensionless quantity A/V(2/3) (V and A are the cell volume and its membrane
      area). This study captures the peculiar motion of Eutreptiella gymnastica with
      simple force distribution.

PMID- 24329473
TI  - Optimal hydrodynamic synchronization of colloidal rotors.
AB  - Synchronization of driven oscillators is a key aspect of flow generation in
      artificial and biological filaments such as cilia. Previous theoretical and
      numerical studies have considered the "rotor" model of a cilium in which the
      filament is coarse grained into a colloidal sphere driven with a given force law
      along a predefined trajectory to represent the oscillating motion of the cilium.
      These studies pointed to the importance of two factors in the emergence of
      synchronization: the modulation of the driving force around the orbit and the
      deformability of the trajectory. In this work it is shown via experiments,
      supported by numerical simulations and theory, that both of these factors are
      important and can be combined to produce strong synchronization (within a few
      cycles) even in the presence of thermal noise. 

PMID- 24329474
TI  - Computing the length of the shortest telomere in the nucleus.
AB  - The telomere length can either be shortened or elongated by an enzyme called
      telomerase after each cell division. Interestingly, the shortest telomere is
      involved in controlling the ability of a cell to divide. Yet, its dynamics
      remains elusive. We present here a stochastic approach where we model this
      dynamics using a Markov jump process. We solve the forward Fokker-Planck equation
      to obtain the steady state distribution and the statistical moments of telomere
      lengths. We focus specifically on the shortest one and we estimate its length
      difference with the second shortest telomere. After extracting key parameters
      such as elongation and shortening dynamics from experimental data, we compute the
      length of telomeres in yeast and obtain as a possible prediction the minimum
      concentration of telomerase required to ensure a proper cell division. 

PMID- 24329475
TI  - Activation energy for mobility of dyes and proteins in polymer solutions: from
      diffusion of single particles to macroscale flow.
AB  - We measure the activation energy Ea for the diffusion of molecular probes (dyes
      and proteins of radii from 0.52 to 6.9 nm) and for macroscopic flow in a model
      complex liquid-aqueous solutions of polyethylene glycol. We cover a broad range
      of polymer molecular weights, concentrations, and temperatures. Fluorescence
      correlation spectroscopy and rheometry experiments reveal a relationship between
      the excess of the activation energy in polymer solutions over the one in pure
      solvent DeltaEa and simple parameters describing the structure of the system:
      probe radius, polymer hydrodynamic radius, and correlation length. DeltaEa varies
      by more than an order of magnitude in the investigated systems (in the range of
      ca. 1-15 kJ/mol) and for probes significantly larger than the polymer
      hydrodynamic radius approaches the value measured for macroscopic flow. We
      develop an explicit formula describing the smooth transition of DeltaEa from the
      diffusion of molecular probes to macroscopic flow. This formula is a reference
      for the quantitative analysis of specific interactions of moving nano-objects
      with their environment as well as active transport. For instance, the power
      developed by a molecular motor moving at constant velocity u is proportional to
      u2exp(Ea/RT).

PMID- 24329476
TI  - Comment on "Origin of cosmic magnetic fields".

PMID- 24329477
TI  - Campanelli replies:.

PMID- 24329478
TI  - Comparison of intestinal metabolism of CYP3A substrates between rats and humans:
      application of portal-systemic concentration difference method.
AB  - 1. Rats are frequently used in pharmacokinetic studies during drug discovery.
      However, there is limited information regarding species differences in intestinal
      availability (Fg) between rats and humans. 2. Here, we directly estimated the
      fraction of dose absorbed in the portal vein (FaFg) of rats for nine CYP3A
      substrates using portal-systemic concentration difference method and compared
      them with human FaFg. No distinct difference in FaFg between the two species was
      observed, and seven of the nine compounds were within a two-fold difference.
      Given that their net fraction of dose absorbed (Fa) are expected to be high, this
      result indicates a moderate correlation in Fg between the two species. 3. In
      contrast, the in vitro intrinsic clearance (CLint,u) in rat intestinal microsomes
      tended to be lower than that in humans, and the correlation between intestinal
      CLint,u and FaFg in rats was poor compared with that in humans. 4. Our finding
      indicates that rats are appropriate animals for evaluation of the intestinal
      absorption and metabolism of CYP3A substrates. However, a degree of caution is
      required when estimating rat Fg from rat intestinal microsomes due to the low
      metabolic activity and the poor correlation between in vitro and in vivo
      intestinal metabolism.

PMID- 24329479
TI  - The role of regression performance on multimodel analysis.
AB  - In this work, we provide suggestions for designing experiments where calibration
      of many models is required and guidance for identifying problematic calibrations.
      Calibration of many conceptual models which have different representations of the
      physical processes in the system, as is done in cross-validation studies or multi
      model analysis, often uses computationally frugal inversion techniques to achieve
      tractable execution times. However, because these frugal methods are usually
      local methods, and the inverse problem is almost always nonlinear, there is no
      guarantee that the optimal solution will be found. Furthermore, evaluation of
      each inverse model's performance to identify poor calibrations can be tedious.
      Results of this study show that if poorly calibrated models are included in the
      analysis, simulated predictions and measures of prediction uncertainty can be
      affected in unexpected ways. Guidelines are provided to help identify problematic
      regressions and correct them. 

PMID- 24329480
TI  - Older people's perceptions of the term elder abuse and characteristics associated
      with a lower level of awareness.
AB  - A national representative survey of 2,021 community-dwelling older people was
      carried out in 2010 using face-to-face interviews. The study examined how the
      term "elder abuse" was understood by this population and identified factors
      associated with lower levels of awareness. Over 80% of this population recognized
      the term elder abuse, and 56% demonstrated specific insight related to
      typologies, locations, and perpetrators of abuse. Less specific responses were
      given by 22% of participants, and a further 21% could not give a reply. Less
      specific or "don't know" responses were independently associated with age 80
      years or older, a lower level of education, impaired physical health, and living
      in economically deprived communities. Despite ongoing public information
      campaigns, there remained a significant portion of older people who may be
      unaware of or have limited insight into elder abuse. This study suggests a need
      for more targeted education campaigns aimed at specific higher-risk groups. 

PMID- 24329481
TI  - Optical coherence tomography: a reliable alternative to invasive histological
      assessment of acute wound healing in human skin?
AB  - BACKGROUND: Gold-standard assessment of acute wound healing has traditionally
      been through histological analysis of biopsied tissue. However, this process is
      invasive with recognized side-effects. Optical coherence tomography (OCT) is a
      noninvasive technique generating high-resolution real-time images of cutaneous
      architecture. OBJECTIVES: To compare OCT with histological assessment of in vivo
      acute wound healing and ascertain the level of agreement between modalities for
      measurement of defined cutaneous structures. METHODS: Punch biopsies (5 mm) were
      harvested from 50 healthy volunteers. Wounds healed by secondary intention until
      they were re-excised 7, 14, 21 or 28 days later depending on random group
      allocation. Wounds were assessed weekly for 6 weeks using OCT and compared with
      histological findings derived from time-matched biopsies. Dimensions of four
      cutaneous structures were measured using both modalities and the level of
      agreement was established by Bland-Altman analysis. The mean greyscale value
      (MGV) of the upper reticular dermis was derived from OCT images at all time
      points. RESULTS: Both techniques showed anatomical congruity in normal and
      wounded skin with correlating architectural changes associated with inflammatory,
      proliferative and remodelling wound healing phases. MGV was significantly
      increased 6 weeks after wounding (P = 0.001) and may represent a novel measure of
      wound fibrosis. Despite good association of histomorphometric values with low but
      consistent bias (range -4.181 to 0.431 MUm), Bland-Altman plots demonstrated poor
      agreement between OCT and histology. CONCLUSIONS: Optical coherence tomography
      enabled accurate assessment of healing tissue comparable with histological
      analysis of biopsy specimens. This noninvasive tool is highly suited to wound
      assessment and may represent a diagnostic alternative to punch biopsies.

PMID- 24329482
TI  - Inactivation of bacteriophage infecting Bacteroides strain GB124 using UV-B
      radiation.
AB  - Ultraviolet-B radiation (280-320 nm) has long been associated with the
      inactivation of microorganisms in the natural environment. Determination of the
      environmental inactivation kinetics of specific indicator organisms [used as
      tools in the field of microbial source tracking (MST)] is fundamental to their
      successful deployment, particularly in geographic regions subject to high levels
      of solar radiation. Phage infecting Bacteroides fragilis host strain GB124 (B124
      phage) have been demonstrated to be highly specific indicators of human fecal
      contamination, but to date, little is known about their susceptibility to UV-B
      radiation. Therefore, B124 phage (n = 7) isolated from municipal wastewater
      effluent, were irradiated in a controlled laboratory environment using UV-B
      collimated beam experiments. All B124 phage suspensions possessed highly similar
      first order log-linear inactivation profiles and the mean fluence required to
      inactivate phage by 4 - log(10) was 320 mJ cm(-2). These findings suggest that
      phage infecting GB124 are likely to be inactivated when exposed to the levels of
      UV-B solar radiation experienced in a variety of environmental settings. As such,
      this may limit the utility of such methods for determining more remote inputs of
      fecal contamination in areas subject to high levels of solar radiation.

PMID- 24329483
TI  - Sepsis in the central nervous system and antioxidant strategies with N
      acetylcysteine, vitamins and statins.
AB  - Sepsis is the complex syndrome characterized by an imbalance between
      proinflammatory and antiinflammatory response to infection. The brain may be
      affected during the sepsis, and acute and long-term brain dysfunctions have been
      observed in both animal models and septic patients. Oxidative stress and
      antioxidant systems may prove the basis underling brain dysfunction in sepsis.
      The antioxidant therapy may be theoretically achieved by the following
      strategies: restoring endogenous antioxidants and nutrients and supplementation
      with exogenous trace elements, vitamins, and nutrients with antioxidant
      proprieties; or administering drugs that reduce oxidative stress, such as N
      acetylcysteine (NAC), vitamins and statins. In the review, we described below the
      involvement of oxidative stress and antioxidants defenses and potential utility
      of these strategies and present data regarding their use in sepsis.

PMID- 24329484
TI  - Inhibition of inflammasome activation improves the impaired pattern of healing in
      genetically diabetic mice.
AB  - BACKGROUND AND PURPOSE: Type 2 diabetes impairs the healing process because of an
      exaggerated and persistent inflammatory response, and an altered expression
      pattern of angiogenic molecules. We investigated the effects of inflammasome
      blockade in diabetes-related wound-healings defects, in genetically diabetic
      mice. EXPERIMENTAL APPROACH: An incisional skin wound model was produced on the
      back of female diabetic C57BL/KsJ-m +/+ Lept(db) mice (db+ /db+) and their normal
      littermates (db+ /m+). Animals were treated daily with two inflammasome blocking
      agents, BAY 11-7082 (20  mg.kg-1 i.p.), or Brilliant Blue G (BBG, 45.5 mg.kg-1
      i.p.), or vehicle. Mice were killed on 3, 6 and 12 days after skin injury to
      measure expression of the NOD-like receptor NLRP3, caspase-1, VEGF, the
      inflammasome adapter protein apoptosis-associated speck-like protein containing a
      caspase recruitment domain (ASC) and the chemokine CXCL12. Wound levels of IL
      1beta and IL-18 were also measured, along with histological assessments of wound
      tissue and the time to complete wound closure. KEY RESULTS: During healing, the
      diabetic mice exhibited increased activation of NLRP3, caspase-1, ASC, IL-1beta
      and IL-18. They also showed a reduced expression of VEGF and CXCL12.Treatment
      with BAY 11-7082 or BBG, to block activation of the inflammasome, decreased the
      levels of pro-inflammatory molecules. Histological evaluation indicated that
      inflammasome blockade improved the impaired healing pattern, at day 12 in
      diabetic mice, along with a decreased time to complete skin healing. CONCLUSIONS
      AND IMPLICATIONS: These data strongly suggest that activation of the NLRP3
      inflammasome is one of the key contributors to the delayed healing of wounds in
      diabetic mice.

PMID- 24329485
TI  - The molecular basis for the development of neural maps.
AB  - Neural development leads to the establishment of precise connectivity in the
      nervous system. By contrasting the information capacities of cortical
      connectivity and the genome, we suggest that simplifying rules are necessary in
      order to create cortical connections from the limited set of instructions
      contained in the genome. One of these rules may be employed by the visual system,
      where connections are formed on the basis of the interplay of molecular gradients
      and activity-dependent synaptic plasticity. We show how a simple model that
      accounts for such interplay can create both neural topographic maps and more
      complex patterns of ocular dominance, that is, the segregated binary mixture of
      projections from two eyes converging in the same visual area. With regard to the
      ocular dominance patterns, we show that pattern orientation may be instructed by
      the direction of the gradients of molecular labels. We also show that the
      periodicity of ocular dominance patterns may result from the interplay of the
      effects of molecular gradients and correlated neural activity. Overall, we
      propose that simple mechanisms can account for the formation of apparently
      complex features of neuronal connections. 

PMID- 24329443
TI  - K(S)0 and Lambda production in Pb-Pb collisions at ?(s(NN))=2.76 TeV.
AB  - The ALICE measurement of K(S)(0) and Lambda production at midrapidity in Pb-Pb
      collisions at ?(s(NN))=2.76 TeV is presented. The transverse momentum (p(T))
      spectra are shown for several collision centrality intervals and in the p(T)
      range from 0.4 GeV/c (0.6 GeV/c for Lambda) to 12 GeV/c. The p(T) dependence of
      the Lambda/K(S)(0) ratios exhibits maxima in the vicinity of 3 GeV/c, and the
      positions of the maxima shift towards higher p(T) with increasing collision
      centrality. The magnitude of these maxima increases by almost a factor of three
      between most peripheral and most central Pb-Pb collisions. This baryon excess at
      intermediate p(T) is not observed in pp interactions at ?s=0.9 TeV and at ?s=7
      TeV. Qualitatively, the baryon enhancement in heavy-ion collisions is expected
      from radial flow. However, the measured p(T) spectra above 2 GeV/c progressively
      decouple from hydrodynamical-model calculations. For higher values of p(T),
      models that incorporate the influence of the medium on the fragmentation and
      hadronization processes describe qualitatively the p(T) dependence of the
      Lambda/K(S)(0) ratio.

PMID- 24329487
TI  - Merging multi-camera data to reduce motion analysis instrumental errors using
      Kalman filters.
AB  - In motion capture systems, markers are often seen by multiple cameras. All
      cameras do not measure the position of the markers with the same reliability
      because of environmental factors such as the position of the marker in the field
      of view or the light intensity received by the cameras. Kalman filters offer a
      general framework to take the reliability of the various cameras into account and
      consequently improve the estimation of the marker position. The proposed process
      can be applied to both passive and active systems. Several reliability models of
      the cameras are compared for the Codamotion active system, which is considered as
      a specific illustration. The proposed method significantly reduces the noise in
      the signal, especially at long-range distances. Therefore, it improves the
      confidence of the positions at the limits of the field of view.

PMID- 24329486
TI  - Long-range connectomics.
AB  - Decoding neural algorithms is one of the major goals of neuroscience. It is
      generally accepted that brain computations rely on the orchestration of neural
      activity at local scales, as well as across the brain through long-range
      connections. Understanding the relationship between brain activity and
      connectivity is therefore a prerequisite to cracking the neural code. In the past
      few decades, tremendous technological advances have been achieved in connectivity
      measurement techniques. We now possess a battery of tools to measure brain
      activity and connections at all available scales. A great source of excitement
      are the new in vivo tools that allow us to measure structural and functional
      connections noninvasively. Here, we discuss how these new technologies may
      contribute to deciphering the neural code. 

PMID- 24329489
TI  - Collective variable description of native protein dynamics.
AB  - The importance of collective motions in proteins, such as hinge-bending motions
      or motions involving domains, has been recognized. Occurrence of such motions and
      their experimental and theoretical studies are reviewed. Normal-mode analysis and
      principal component analysis are powerful theoretical tools for studying such
      motions. The former is based on the assumption of harmonicity of the dynamics,
      while the latter is valid even when the dynamics is highly anharmonic. The
      results of the latter analysis indicate that most important conformational events
      are taking place in a conformational subspace spanned by a rather small number of
      principal modes, and this important subspace is also spanned by a small number of
      normal modes. The normal-mode refinement method of protein X-ray crystallography,
      which is developed based on the concept of the above important subspace, is
      discussed. 

PMID- 24329488
TI  - Osteoarthritis of the hand I: aetiology and pathogenesis, risk factors,
      investigation and diagnosis.
AB  - OBJECTIVE: Osteoarthritis (OA) of the hand can be a debilitating condition that
      hinders an individual's quality of life. With multiple joints within the hand
      that are commonly affected OA, an individual's ability to use their hand in
      everyday movements become more limited. The article aims to review literature on
      the aetiology and pathogenesis of OA, risk factors, characteristics of hand OA
      and the steps of diagnosis. KEY FINDINGS: The aetiology and pathogenesis of OA,
      in particular hand OA, is not fully understood. However, it is known that several
      factors play a role. Environmental factors, such as stress from mechanical
      loading, especially to vulnerable joints predispose individuals to developing OA.
      Extracellular matrix changes in protein levels have also been noted in
      individuals with OA. Linked to hand OA development are boney enlargements
      (Herbeden's and Bouchard's nodes). Several risk factors for OA include: age,
      obesity, gender, smoking, genetics, diet and occupation. Various diagnostic
      methods include a combination of using radiographic methods, clinical
      presentation, a number of developed measurements and scales. SUMMARY: With OA
      having several risk factors and various causes and contributing elements, it is
      important to elucidate the pathogenesis of OA and determine exactly how risk
      factors play a role in its development. Because of the contributions from several
      elements, diagnosis is best when it uses multiple methods. In turn, understanding
      OA and making better diagnoses could lead to improved management of the condition
      through both pharmacological and non-pharmacological interventions.

PMID- 24329490
TI  - The ICF Core Sets for hearing loss: researcher perspective, Part II: Linking
      outcome measures to the International Classification of Functioning, Disability
      and Health (ICF).
AB  - OBJECTIVE: To link outcome measures used in audiological research to the ICF
      classification and thereby describe audiological research from the ICF
      perspective. DESIGN: Through a peer-reviewed or a joint linking procedure, link
      outcome measures to the ICF classification system using standardized ICF linking
      rules. Additional linking rules were developed in combination with the
      established rules to overcome difficulties when connecting audiological data to
      ICF. Absolute and relative frequencies of ICF categories were reported. STUDY
      SAMPLE: The identified outcome measures from the previous study (Part I)
      constituted the empirical material. RESULTS: In total, 285 ICF categories were
      identified. The most prevalent categories were related to listening, hearing
      functions, auditory perceptions, emotions and the physical environment, such as
      noise and hearing aids. Categories related to communication showed lower relative
      frequencies, as did categories related to the social and attitudinal environment.
      CONCLUSIONS: Based on the linked outcome measures, communication as a research
      topic is subordinated to other research topics. The same conclusion can be drawn
      for research targeting the social and attitudinal environment of adults with HL.
      Difficulties in the linking procedure were highlighted and discussed, and
      suggestions for future revisions of the ICF from the audiological perspective
      were described.

PMID- 24329491
TI  - User-operated speech in noise test: implementation and comparison with a
      traditional test.
AB  - OBJECTIVE: The purpose of this study was to implement and evaluate a user
      operated speech in noise test. DESIGN: The test is based on the Danish speech
      material Dantale II, which consists of five words sentences ( Wagener et al, 2003
      ). For each word presented the subject selected a response from ten alternative
      words. Two versions of the test were made: one with and one without the
      possibility that for each word presented the subject could answer "I do not know"
      (?-button). Using a listening test the two versions were evaluated against a
      traditional test, where the subjects orally repeated the words that were
      perceived. STUDY SAMPLE: Twenty-four normal-hearing subjects. RESULTS: The speech
      intelligibility as a function of the signal-to-noise ratio can be described by
      logistic functions in the different user-operated tests and in the traditional
      test. The logistic parameters obtained from the user-operated test with the ?
      button agree with the parameters obtained in a traditional test. The homogeneity
      of the speech material is uninfluenced when the material is used in a user
      operated test. CONCLUSIONS: It is reasonable to use the Dantale II speech
      material for a user-operated speech in noise test, and the use of the ?-button is
      favourable.

PMID- 24329492
TI  - Androgen receptor inducing bladder cancer progression by promoting an epithelial
      mesenchymal transition.
AB  - The study investigated the role of androgen receptor (AR) as a potential target
      for the treatment of bladder cancer in regulating epithelial-mesenchymal
      transition or transformation (EMT). Cell proliferation, and migration capacity
      were determined in bladder cancer T24 cells treated with small interfering RNA
      directed against AR, and expression levels of E-cadherin, beta-catenin and N-
      cadherin were assessed using quantitative reverse transcription PCR (qRT-PCR).
      Tumour cell growth was evaluated in vivo in T24 tumour-bearing nude mice
      receiving electroporation-assisted administration of anti-AR small interfering
      RNA. It was found that low AR expression decreased proliferation and migration of
      bladder cancer cells. In vivo experiments showed that silencing AR expression
      significantly suppressed AR-positive bladder tumour growth with decreased cell
      proliferation. Low AR level of T24 bladder cancer cells treated with
      dehydrotestosterone (DHT) decreased expression of E-cadherin, beta-catenin and N
      cadherin expression, indicating a strong sensitivity to the EMT and In cells with
      low AR content, TGF-beta induced down-regulation of E-cadherin and beta-catenin.
      It is concluded that suppression of AR expression decreased the production of TGF
      beta, inhibiting EMT and bladder cancer cell growth in vitro and in vivo,
      implying that its use might be a potential therapeutic target for the treatment
      of bladder cancer. 

PMID- 24329493
TI  - Good response of low-fat/high-protein diet in a patient with chyluria.
AB  - Chyluria is an inappropriate urinary excretion of chyle that turns the urine
      milky. A nutritional approach based on low-fat/high-protein content diet
      associated or not with medium-chain triglyceride (MCT) showed to be an efficient
      conservative treatment to improve the milky urine appearance in a patient with
      chyluria. CASE REPORT: A 30-year-old female patient was admitted with chyluria of
      unknown etiology. An ureteropyeloscopy revealed a single lesion in each kidney,
      both with linear aspect and measuring 5 mm in extension. These lesions were
      located close to the renal papillae and were leaking a cloudy and milky fluid.
      Both lesions were laser cauterized followed by improvement of the milky urine.
      However, the chyluria relapsed after few months and a low-fat/high-protein
      content diet with 10 g of soybean oil to meet the requirements essential fatty
      acids (EFA) and with MCT from coconut oil as alternative to prepare foods was
      started. Few weeks later the patient returned reporting consistent improvement of
      the milky urine appearance related with the use of the diet. However since the
      diet was tasteless and time consuming to prepare, she reported low compliance to
      diet with MCT and the milky urine relapsed. The MCT was discontinued and the diet
      with EFA source was maintained with better compliance. Since then the chyluria
      remains in remission. In conclusion, the dramatic improvement of the milky urine
      with low-fat/high-protein diet with EFA source observed in our patient
      demonstrates that this nutritional approach is efficient with fast results to
      treat chyluria during long term.

PMID- 24329496
TI  - Development and validation of a collaborative behaviors objective assessment tool
      for end-of-life communication.
AB  - CONTEXT: Helping families make end-of-life decisions requires close collaboration
      between physicians and nurses. However, medical and nursing students have little
      formal training in how to collaborate in this task, and few instruments are
      available to measure collaborative behaviors. OBJECTIVES: The objective of this
      project was to develop and validate observational assessment tools to measure
      specific interprofessional competencies in medical and nursing students related
      to end-of-life discussions. DESIGN: A literature search for evidence-based
      guidelines and competencies and focus groups with an expert panel of nurses and
      physicians were used to outline best collaborative practice behaviors for nurses
      and physicians in an end-of-life decision making simulation. The panel used these
      practice-behavior checklists to rate videotaped student scenarios and then
      refined the checklists for validity and clarity until the tools had acceptable
      inter-rater reliability. SETTING: The setting was a workshop teaching end-of-life
      communication to third-year nursing and medical students. MEASUREMENTS: Inter
      rater reliability was measured using percent agreement and kappa; internal
      consistency was measured using Cronbach's alpha. RESULTS: Collaborative behaviors
      objective assessment tools (CBOATs) for nursing and medical students were
      developed. For the medical CBOAT we found 85% agreement between raters, with an
      overall kappa of 0.744 and Cronbach's alpha of 0.806. For the nursing CBOAT there
      was 81% agreement, with a kappa of 0.686 and Cronbach's alpha of 0.845.
      CONCLUSIONS: Development of an end-of-life CBOAT clarified the important
      collaborative behaviors needed by physician and nurse. The resulting instruments
      provide a helpful guide for teaching interprofessional sessions related to the
      end of life and measuring student outcomes using an objective strategy.

PMID- 24329494
TI  - Caveolin 1 is critical for abdominal aortic aneurysm formation induced by
      angiotensin II and inhibition of lysyl oxidase.
AB  - Although AngII (angiotensin II) and its receptor AT1R (AngII type 1 receptor)
      have been implicated in AAA (abdominal aortic aneurysm) formation, the proximal
      signalling events primarily responsible for AAA formation remain uncertain.
      Caveolae are cholesterol-rich membrane microdomains that serve as a signalling
      platform to facilitate the temporal and spatial localization of signal
      transduction events, including those stimulated by AngII. Cav1 (caveolin 1)
      enriched caveolae in vascular smooth muscle cells mediate ADAM17 (a disintegrin
      and metalloproteinase 17)-dependent EGFR (epidermal growth factor receptor)
      transactivation, which is linked to vascular remodelling induced by AngII. In the
      present study, we have tested our hypothesis that Cav1 plays a critical role for
      the development of AAA at least in part via its specific alteration of AngII
      signalling within caveolae. Cav1-/- mice and the control wild-type mice were co
      infused with AngII and beta-aminopropionitrile to induce AAA. We found that Cav1
      /- mice with the co-infusion did not develop AAA compared with control mice in
      spite of hypertension. We found an increased expression of ADAM17 and enhanced
      phosphorylation of EGFR in AAA. These events were markedly attenuated in Cav1-/-
      aortas with the co-infusion. Furthermore, aortas from Cav1-/- mice with the co
      infusion showed less endoplasmic reticulum stress, oxidative stress and
      inflammatory responses compared with aortas from control mice. Cav1 silencing in
      cultured vascular smooth muscle cells prevented AngII-induced ADAM17 induction
      and activation. In conclusion, Cav1 appears to play a critical role in the
      formation of AAA and associated endoplasmic reticulum/oxidative stress,
      presumably through the regulation of caveolae compartmentalized signals induced
      by AngII.

PMID- 24329495
TI  - The microbiome and regulation of mucosal immunity.
AB  - The gastrointestinal tract is a mucosal surface constantly exposed to foreign
      antigens and microbes, and is protected by a vast array of immunologically active
      structures and cells. Epithelial cells directly participate in immunological
      surveillance and direction of host responses in the gut and can express numerous
      pattern recognition receptors, including Toll-like receptor 5 (TLR5), TLR1, TLR2,
      TLR3, TLR9, and nucleotide oligomerization domain 2, as well as produce
      chemotactic factors for both myeloid and lymphoid cells following inflammatory
      stimulation. Within the epithelium and in the underlying lamina propria resides a
      population of innate lymphoid cells that, following stimulation, can become
      activated and produce effector cytokines and exert both protective and pathogenic
      roles during inflammation. Lamina propria dendritic cells play a large role in
      determining whether the response to a particular antigen will be inflammatory or
      anti-inflammatory. It is becoming clear that the composition and metabolic
      activity of the intestinal microbiome, as a whole community, exerts a profound
      influence on mucosal immune regulation. The microbiome produces short-chain fatty
      acids, polysaccharide A, alpha-galactosylceramide and tryptophan metabolites,
      which can induce interleukin-22, Reg3gamma, IgA and interleukin-17 responses.
      However, much of what is known about microbiome-host immune interactions has come
      from the study of single bacterial members of the gastrointestinal microbiome and
      their impact on intestinal mucosal immunity. Additionally, evidence continues to
      accumulate that alterations of the intestinal microbiome can impact not only
      gastrointestinal immunity but also immune regulation at distal mucosal sites. 

PMID- 24329497
TI  - Mindfulness-based cognitive therapy with older adults: an exploratory study.
AB  - An 8-week mindfulness-based cognitive therapy (MBCT) group for older adults with
      depression and/or anxiety is described. This article is based on an exploratory
      study of this therapeutic approach and changes in participants' symptoms
      associated with participation. Pre-post data from 5 MBCT groups showed
      significant improvements in reported anxiety, ruminative thoughts, and sleep
      problems and a reduction in depressive symptoms. Case examples are presented to
      illustrate these symptom changes. Findings showed that this nonpharmacological
      intervention is acceptable to older adults and is associated with positive
      changes. Suggestions are provided for both practitioners and researchers
      interested in using MBCT with older adults. 

PMID- 24329498
TI  - A cafe on the premises of an aged care facility: more than just froth?
AB  - OBJECTIVE: The aim of this study was to explore the value of a cafe on the
      premises of a large aged care facility for the residents and their family and
      friends. METHODS: Interviews were conducted with 11 residents and nine
      family/friends. Interpretive descriptive methodology was used in the data
      analysis. The value of the cafe for the participants was established according to
      five major themes: "A place to go", "opportunities for relating", "opportunities
      for being and doing", "a sense of the ordinary", and "a sense of self". RESULTS:
      As a place the cafe was valued for both its pleasant environment and warm
      friendly atmosphere where participants experienced a sense of belonging to a
      community. The cafe generated a hub of activity, which provided stimulation and
      the activity of choosing, buying, and sharing food and drink contributed to the
      maintenance of life roles, family life, and connections to the community.
      CONCLUSIONS: The cafe provided a myriad of opportunities for participation in
      relationships and the creation and maintenance of social networks. This
      participation reinforced a sense of self and of being ordinary.

PMID- 24329499
TI  - Current status of prediction of drug disposition and toxicity in humans using
      chimeric mice with humanized liver.
AB  - 1. Human-chimeric mice with humanized liver have been constructed by
      transplantation of human hepatocytes into several types of mice having genetic
      modifications that injure endogenous liver cells. Here, we focus on liver
      urokinase-type plasminogen activator-transgenic severe combined immunodeficiency
      (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so
      far indicate that drug metabolism, drug transport, pharmacological effects and
      toxicological action in these mice are broadly similar to those in humans. 2.
      Expression of various drug-metabolizing enzymes is known to be different between
      humans and rodents. However, the expression pattern of cytochrome P450, aldehyde
      oxidase and phase II enzymes in the liver of human-chimeric mice resembles that
      in humans, not that in the host mice. 3. Metabolism of various drugs, including S
      warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in
      human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host
      mouse enzymes, and thus resembles that in humans. 4. Pharmacological and
      toxicological effects of various drugs in human-chimeric mice are also similar to
      those in humans. 5. The current consensus is that chimeric mice with humanized
      liver are useful to predict drug metabolism catalyzed by cytochrome P450,
      aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some
      remaining issues are discussed in this review.

PMID- 24329500
TI  - Effect of triacontanol on the pharmacokinetics of docetaxel in rats associated
      with induction of cytochrome P450 3A1/2.
AB  - Triacontanol was confirmed to have a potential anti-cancer effect, the aim was to
      assess whether the co-administration of triacontanol alters the exposure of
      docetaxel via inducing hepatic CYP3A1/2 activity. The concentration of docetaxel
      in rats pretreated with triacontanol for seven successive days was determined,
      and the expression levels of CYP3A protein and mRNA were analyzed by the western
      blot and real time polymerase chain reaction (RT-PCR) technique, respectively. 2.
      The concentrations of docetaxel in rats pretreated with triacontanol were
      decreased, with 61.5%, 61.9% decrease in AUC0-24h and 65.7%, 54.9% reduction in
      Cmax (120 and 180 mg kg(-1), respectively) compared with the control. Hepatic
      clearance of docetaxel was enhanced in vitro and in vivo at dosage of 120 and 180
      mg kg(-1), and CYP3A activity was up-regulated by measuring the formation rate of
      1-hydroxymidazolam. Triacontanol preferentially induced protein expression level
      of CYP3A2 in a dose-dependent manner and of CYP 3A1 at dosage of 120 and 180 mg
      kg(-1). The mRNA expression of CYP3A1 was moderately different with the western
      blot results, but the trends appeared similar. CYP3A2 mRNA level was not markedly
      affected by triacontanol. 3.  The significant triacontanol-docetaxel interaction
      was largely due to the induction of CYP3A1/2, which brought useful information in
      the clinical therapy when the combination is administered in human.

PMID- 24329502
TI  - Gold-free ternary III-V antimonide nanowire arrays on silicon: twin-free down to
      the first bilayer.
AB  - With the continued maturation of III-V nanowire research, expectations of
      material quality should be concomitantly raised. Ideally, III-V nanowires
      integrated on silicon should be entirely free of extended planar defects such as
      twins, stacking faults, or polytypism, position-controlled for convenient device
      processing, and gold-free for compatibility with standard complementary metal
      oxide-semiconductor (CMOS) processing tools. Here we demonstrate large area
      vertical GaAsxSb1-x nanowire arrays grown on silicon (111) by molecular beam
      epitaxy. The nanowires' complex faceting, pure zinc blende crystal structure, and
      composition are mapped using characterization techniques both at the nanoscale
      and in large-area ensembles. We prove unambiguously that these gold-free
      nanowires are entirely twin-free down to the first bilayer and reveal their three
      dimensional composition evolution, paving the way for novel infrared devices
      integrated directly on the cost-effective Si platform. 

PMID- 24329501
TI  - Epithelial-differentiated adipose-derived stem cells seeded bladder acellular
      matrix grafts for urethral reconstruction: an animal model.
AB  - The limited amount of available epithelial tissue is considered a main cause of
      the high rate of urethral reconstruction failures. The aim of this study was to
      investigate whether epithelial-differentiated rabbit adipose-derived stem cells
      (Epith-rASCs) could play a role of epithelium in vivo functionally and be a
      potential substitute of urothelium. Substitution urethroplasty was performed to
      repair an anterior urethral defect in male New Zealand rabbits using Epith-rASCs
      seeded bladder acellular matrix grafts (BAMGs) after 5-bromo-2'-deoxyuridine
      (BrdU) labeling, based on the in vitro epithelial induction system we previously
      described. Urethroplasty with cell-free BAMGs and with undifferentiated rASCs
      (Und-rASCs) seeded BAMGs were performed as controls. After surgery, a notable
      amelioration of graft contracture and recovery of urethral continuity were
      observed in the Epith-rASCs/BAMG group by retrograde urethrograms and macroscopic
      inspection. Immunofluorescence revealed that the BrdU-labeled Epith-rASCs/Und
      rASCs colocalized with cytokeratin 13 or myosin. Consistent with the results of
      western blotting, at early postimplantation stage, the continuous epithelial
      layer with local multilayered structure was observed in the Epith-rASCs/BAMG
      group, whereas no significant growth and local monolayer growth profile of
      epithelial cells were observed in the BAMG and Und-rASCs/BAMG group,
      respectively. The results showed that Epith-rASCs could serve as a potential
      substitute of urothelium for urethral tissue engineering and be available to
      prevent lumen contracture and subsequent complications including recurrent
      stricture. 

PMID- 24329503
TI  - A preliminary study in Wistar rats with enniatin A contaminated feed.
AB  - A 28-day repeated dose preliminary assay, using enniatin A naturally contaminated
      feed through microbial fermentation by a Fusarium tricinctum strain, was carried
      out employing 2-month-old female Wistar rats as in vivo experimental model. In
      order to simulate a physiological test of a toxic compound naturally produced by
      fungi, five treated animals were fed during 28 days with fermented feed. As
      control group, five rats were fed with standard feed. At the 28th day, blood
      samples were collected for biochemical analysis and the gastrointestinal tract,
      liver and kidneys were removed from each rat for enniatin A detection and
      quantitation. Digesta were collected from stomach, duodenum, jejunum, ileum and
      colon. Enniatin A present in organs and in biological fluids was analyzed by
      liquid chromatography-diode array detector (LC-DAD) and confirmed by LC-mass
      spectrometry linear ion trap (MS-LIT); also several serum biochemical parameters
      and a histological analysis of the duodenal tract were performed. No adverse
      effects were found in any treated rat at the enniatin A concentration (20.91
      mg/kg bw/day) tested during the 28-day experiment. Enniatin A quantitation in
      biological fluids ranged from 1.50 to 9.00 mg/kg, whereas in the gastrointestinal
      organs the enniatin A concentration ranged from 2.50 to 23.00 mg/kg. The high
      enniatin A concentration found in jejunum liquid and tissue points to them as an
      absorption area. Finally, two enniatin A degradation products were identified in
      duodenum, jejunum and colon content, probably produced by gut microflora.

PMID- 24329504
TI  - Biochemical alteration of hepatic functions by histamine H3-receptor agonist and
      antagonist in immunized rabbits.
AB  - AIM: The aim of our study was to investigate the functional roles of H3R agonist
      and antagonist in the development of hepatic functions impairment in immunized
      rabbits. METHODS: The study comprised of six groups containing 18 rabbits in
      each. Group-I (negative control) and group-II (positive control) received sterile
      distilled water intramuscularly while Group III-VI received histamine (100 ugkg
      1, s.c.), R-[-]-alpha-methylhistamine (H3R-agonist, 10 ugkg-1, s.c.),
      iodophenpropit (H3R-antagonist, 1 ugkg-1, i.m.), and the combination of
      iodophenpropit (1 ugkg-1, i.m.) plus histamine (100 ugkg-1, s.c.), respectively,
      b.i.d. (12 hours [8 am and 8 pm]) for 10 days. Groups II-VI were immunized on day
      3 with intravenous injection of sheep red blood cells (1*109 cells/ml). RESULTS:
      On each experimental day, the mean values of serum enzymes and bilirubin in group
      I and group-II showed no changes while in groups III, IV, V, and VI, these
      enzymes and bilirubin levels showed significant changes (p<0.05), when compared
      with their values within the group. Profile of ALT and AST production revealed
      that ALT and AST levels moderately were changed due to degeneration of the liver.
      CONCLUSION: Our results suggest that R-[-]-alpha-methylhistamine showed moderate,
      and histamine and iodophenpropit showed mild degeneration of liver functions;
      while iodophenpropit plus histamine showed hepatic functions similar to control
      group. This study suggests that H3R antagonist in combination with histamine may
      be a non-toxic therapeutic target for histamine research (Fig. 7, Ref. 28). Text
      in PDF www.elis.sk.

PMID- 24329505
TI  - The effects of L-carnitine and N-acetylcysteine on carbontetrachloride induced
      acute liver damage in rats.
AB  - AIM: To investigate the effects of L-carnitine (LCAR) and N-acetylcysteine (NAC)
      on carbon tetrachloride (CCl4)-induced acute liver damage in rats. MATERIAL AND
      METHODS: Totally, 40 rats in 5 groups were included in the study. The first group
      was the control group. Group 2 received CCl4 (2 ml/kg). Group 3 was given CCl4 +
      NAC (150 mg/kg). The rats in the Group 4 were administered CCl4 + LCAR (100
      mg/kg), and the rats in the Group 5 were given CCl4 + NAC + LCAR. Both CCl4 and
      the treatment protocols were administered via intraperitoneal route for 10 days.
      Tissue oxidative stress and antioxidant markers were investigated in liver tissue
      and serum liver enzymes were measured. RESULTS: The levels of blood liver enzymes
      (ALT and AST) increased significantly in the Group 2. However, they decreased
      markedly in all treatment groups. While malondialdehyde and myeloperoxidase
      levels in the liver tissue samples increased significantly in the 2nd group,
      those levels were determined to be decreased significantly in all treatment
      groups. When the liver tissue antioxidant levels were evaluated; reduced
      glutathione and catalase decreased markedly in the 2nd group, but increased
      following the administration of NAC and LCAR. The activities of liver tissue
      superoxide dismutase did not differ significantly among the groups. In the
      histopathologic evaluation of liver tissues, on the other hand, diffuse
      hepatosteatosis was observed in all groups except the control group and there was
      no significant difference among the groups from the point of steatosis.
      CONCLUSION: LCAR and NAC were concluded to have beneficial effects on the acute
      liver damage induced by CCl4 administration (Tab. 1, Fig. 5, Ref. 52). Text in
      PDF www.elis.sk.

PMID- 24329506
TI  - Effect of growth hormone on bone status in growth hormone-deficient adults.
AB  - BACKGROUND: Growth hormone deficiency (GHD) is associated with reduced bone
      mineral content and increased risk of osteoporotic fractures. Reduced peak bone
      mass might explain the low bone mineral density (BMD) among patients with
      childhood onset GHD (CO-GHD) whilst the cause of osteopenia in adult-onset GHD
      (AO-GHD) is not fully understood. OBJECTIVES: Prospective multicentric study to
      asses bone status in GHD adults after two years of recombinant growth hormone
      replacement treatment. METHODS: In 94 GHD adults (49 men; O 34.5 yrs) we have
      measured BMD and bone markers (CTX, osteocalcin) during two years of rhGH
      treatment (at baseline, after 3 and 6 months, and after 1 and 2 years). Patients
      were adequately substituted for GHD and other pituitary deficiencies. RESULTS: We
      have observed an increase in BMD-lumbar spine: n=42, 0.8155 ->0.9418 g/cm2,
      p<0.0001; femoral neck n=41; 0.8468 ->0.9031; p= 0.0004; BMD-whole body 1.0179 
      >1.0774; p=0.0003. We have compared gender difference: BMD-L-spine by 15.8 % in
      men (n=21) and by 5.6 % in women (n=19) (p= 0.008); BMD-femoral neck increased by
      11.03 % in men and by about 3.0 % in women (p=0.032). In women, the initial
      decrease in BMD was recorded after 3 months. CO-GHD adults yielded a higher
      increase in BMD -L-spine (16.6 %, p=0.022). A correlation exists between IGF-I
      levels and BMD in lumbar spine (1st year: R=0.348, p=0.026; 2nd year: R= 0.33,
      p=0.0081) and between IGF-I and osteocalcin (1st year: R=0.383; p=0.0038).
      CONCLUSION: Two-year therapy with recombinant human growth hormone improved bone
      status. IGF-I appears to be a good indicator of rhGH effect on bone (Tab. 3, Fig.
      9, Ref. 36). Text in PDF www.elis.sk.

PMID- 24329507
TI  - Impact of intracranial pressure measurement on survival in patients with severe
      traumatic brain injury.
AB  - OBJECTIVE: The aim of the study was to assess (i) a group of patients with
      established intracranial pressure (ICP) sensor in severe brain injuries scoring 3
      points of Glasgow Coma Scale, (ii) mortality and survival of the patients within
      periods of 7, 30, 180 and 270 days; and (iii) predictive value of intracranial
      pressure and cerebral perfusion pressure for short and long-term survival of
      patients with traumatic brain injury. MATERIAL AND METHODS: The group consisted
      of 61 patients with trauma brain injury scoring 3 points of Glasgow Coma Scale,
      continuously monitored for intracranial pressure cerebral perfusion pressure at
      the Intensive Care Unit setting in Nove Zamky. Follow-up period was between 7 and
      270 days. Measured values and other recorded data were analysed using methods of
      descriptive and inferential statistics. RESULTS: ICP values below 20 mmHg were
      associated with a significantly lower risk of death of an individual patient at
      particular time. Accordingly, cerebral perfusion pressure values above 70 mmHg
      during 0-2 days were associated with a significantly higher long-term survival.
      Overall mortality rates within 30 days showed no peaks on survival curves. In the
      periods of 0-7 days, within 30 days, and between 30 and 180 days we recorded 24,
      51 and 2 deaths, respectively. In the period between 180 and 270 days, mortality
      was zero. CONCLUSION: The survival of trauma brain injury patients depends on the
      speed and quality of pre-hospital care and adequate follow-up treatment at
      specialized intensive care units. High levels of intracranial pressure and low
      cerebral perfusion pressure values in the early period after brain injury are
      closely related to mortality of patients within 30 days. Intracranial pressure
      monitoring may help to avoid problems and allow intervention before they become
      life-threatening (Tab. 4, Fig. 4, Ref. 23). Text in PDF www.elis.sk.

PMID- 24329508
TI  - sTREM-1 in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis,
      effect of smoking and inflammation.
AB  - Soluble TREM-1 (sTREM-1; Triggering receptor expressed on myelocytes) is a new
      inflammatory marker indicating the intensity of myeloid cells activation and the
      presence of infection caused by extracellular bacteria and mould.The aim of our
      work was to detect and compare the levels of sTREM-1 in bronchoalveolar lavage
      fluid (BALF) in patients with pulmonary sarcoidosis (PS) and other ILD of non
      infectious origin. The sTREM-1 levels were assessed by ELISA in 46 patients
      suffering from ILD, out of them 22 with PS. The levels of BALF sTREM-1 in PS
      patients were higher than in control group of ILD patients of non-infectious
      origin, however, the difference was not statistically significant. Since all PS
      patients except one were non-smokers we compared non-smokers PS with non-smokers
      ILD patients and found four times higher levels of BALF sTREM-1 in PS patients (P
      = 0.001). We also recorded the effect of smoking, ILD smokers had higher sTREM-1
      levels than non-smokers (P = 0.0019). Higher concentrations of sTREM-1 were
      detected in BALF of patients with lymphadenopathy and with elevated inflammatory
      markers in BALF. Our results show that BALF sTREM-1 could be a good inflammatory
      marker and could help in diagnosis and PS monitoring. Detection of sTREM-1 in
      BALF indirectly points to myeloid cells activation in the lungs and helps to
      complete the information about the number of myeloid cells commonly determined in
      BALF with additional information concerning the intensity of their activation.
      This is the first study that analyses BALF sTREM-1 levels in patients with PS
      (Tab. 8, Ref. 28). Text in PDF www.elis.sk.

PMID- 24329509
TI  - Glycogen phosphorylase BB as a potential marker of cardiac toxicity in patients
      treated with anthracyclines for acute leukemia.
AB  - OBJECTIVES: The aim of the presented study was to assess plasma glycogen
      phosphorylase BB (GPBB) concentrations in acute leukemia patients treated with
      anthracycline containing chemotherapy. BACKGROUND: Anthracyclines represent the
      highest risk for development of cardiotoxicity. GPBB belongs to proposed
      biomarkers of cardiac injury with a very limited experience in this context.
      METHODS: Totally, 24 adult patients with acute leukemia were enrolled. Plasma
      GPBB concentrations were measured by ELISA at diagnosis (before chemotherapy),
      after first chemotherapy with anthracyclines and 6 months after the completion of
      treatment. The cut-off value for GPBB positivity was 10.00 ug/L as recommended by
      the manufacturer. RESULTS: Before chemotherapy, the mean plasma GPBB
      concentration was 5.25+/-3.81 ug/L, increased above the cut-off in 1 patient (4.2
      %). After the first chemotherapy, the mean GPBB was 6.61+/-5.54 ug/L, positive in
      7 (29.2 %) patients. Six months after treatment, the mean GPBB was 10.06+/-11.41
      ug/L, positive in 8 (33.3 %) patients. Six months after treatment, we found a
      significant correlation between elevation in GPBB and diastolic left ventricular
      dysfunction on echocardiography (r=0.621; p<0.0001). The differences in plasma
      GPBB between healthy blood donors and patients treated for acute leukemia were
      statistically significant (p<0.01 in all cases). CONCLUSION: Our results
      suggested that GPBB could become a potential biomarker for detection of acute and
      chronic cardiotoxicity associated with anthracycline containing chemotherapy. The
      predictive value for development of treatment-related cardiomyopathy in future is
      not clear and will be evaluated during the follow-up. Further studies are needed
      to define the potential role of GPBB and other biomarkers in the assessment of
      chemotherapy-induced cardiotoxicity (Ref. 21). Text in PDF www.elis.sk.

PMID- 24329510
TI  - Dynamics of fertility in patients on waiting list for kidney transplantation.
AB  - OBJECTIVES: To evaluate the presence of hormonal abnormalities and fertility
      disorders in patients with chronic kidney disease (CKD) awaiting renal
      transplantation. METHODS: From September 2009 to April 2011 all male patients
      with CKD awaiting kidney transplantation were investigated. The following tests
      were performed: semen analysis, serum concentration of testosterone, SHBG, LH,
      FSH and prolactin. Differences in hormone levels and sperm count parameters were
      statistically evaluated between the control group and the patient group. RESULTS:
      The group of patients consisted of 74 and the control group of 41 men. Average
      testosterone levels were lower in patients compared to control group. In patients
      significantly higher levels of SHBG, LH, FSH and PRL were found, and
      statistically significantly lower ejaculate volume, total sperm count, sperm
      concentration, total and progressive sperm motility and sperm morphology than in
      the control group. Within the group of patients a negative correlation between
      testosterone and PRL was found and a positive correlation between testosterone
      and total sperm motility and morphology. A negative correlation was detected
      between the duration of haemodialysis and testosterone, sperm concentration,
      total and progressive motility and sperm morphology. CONCLUSION: Significant
      changes in hormone levels and impaired fertility are found in haemodialyzed
      patients on a waiting list for kidney transplantation. The dynamics of these
      changes are dependent on the duration of haemodialysis (Tab. 4, Fig. 2, Ref. 15).
      Text in PDF www.elis.sk.

PMID- 24329511
TI  - Enterococcus faecalis and Candida albicans in the dental root canal and
      periapical infections.
AB  - OBJECTIVE: The aim of the present study was to examine the prevalence of
      Enterococcus faecalis and Candida albicans in endodontic infections. METHODS:
      Samples for microbiological examination were collected from 32 patients with deep
      dental caries, infected dental root canal, or periapical infection. RESULTS:
      Cultivation of the dental samples yielded four strains of Enterococcus faecalis
      (12.5 %), and three strains of Candida albicans (9.4 %). All Enterococcus
      faecalis isolates were susceptible to ampicillin, one isolate was resistant to
      tetracycline, two to erythromycin and azithromycin (additional 2 had intermediate
      susceptibility), and one strain had intermediate susceptibility to ciprofloxacin
      and moxifloxacin. CONCLUSION: We conclude that Enterococcus faecalis and Candida
      albicans can participate in the dental root canal and periapical infections, and
      the use of effective irrigant solutions and intracanal medicaments active against
      these microbes is important in order to prevent endodontic therapy failures.
      Unexpected was the isolation of C. albicans from a nine-year-old child with
      periodontitis apicalis. This finding must draw attention to the possibility that
      even at such a young age, this microorganism could be a potential etiological
      agent in endodontic infections (Tab. 2, Ref. 34). Text in PDF www.elis.sk.

PMID- 24329512
TI  - A high oxidative stress index predicts endothelial dysfunction in young male
      smokers.
AB  - Experimental studies have shown that smoking was related to endothelial
      dysfunction via oxidative stress. However, the degree of oxidative stress to be
      associated with endothelial dysfunction is unknown. Oxidative stress index (OSI)
      might be a useful and easy way of determining the endothelial dysfunction. Hence,
      we aimed to evaluate the relationship between OSI and flow mediated dilatation
      (FMD) in smoking healthy male volunteers. Eighty smoking healthy male volunteers
      were enrolled in the study. Participants were classified as having normal and
      abnormal FMD response. In an univariate analysis; systolic and diastolic blood
      pressures, C-reactive protein (CRP), low-density lipoprotein cholesterol, OSI and
      lipid peroxidation (LPO) levels were predictive for abnormal FMD response. In a
      multivariable logistic regression analysis with forward stepwise method, OSI (OR:
      3.194, 95% CI: 1.710-5.966, p<0.001) and CRP (OR: 2.082, 95% CI: 1.101-3.939, p
      0.024) were found to be independent parameters for predicting abnormal FMD
      response in young male smokers. The optimal cut-off value of OSI for detecting
      abnormal FMD response was found to be >3.35, with 100 % sensitivity and 84.1 %
      specificity. We have shown that critical endothelial dysfunction can easily be
      detected by OSI in individuals, at risk for developing coronary artery disease,
      such as smokers (Tab. 3, Fig. 3, Ref. 30). Text in PDF www.elis.sk.

PMID- 24329513
TI  - Butyrylcholinesterase as a biochemical marker.
AB  - Butyrylcholinesterase (BChE) is an enzyme expressed in multiple organs and
      abundant in plasma. BChE can fluctuate in course of several reasons while both
      hypercholiensterasemia and hypocholinesterasemia are known. Considering evidence
      of BChE activity alterations, hepatocellular carcinoma, chronic liver diseases
      and poisoning with carbamates or organophosphates can be diagnosed by activity
      assay. BChE is responsible for detoxification reactions, and the compounds such
      as cocaine, succinylcholine, and acetylsalicylic acid are degraded in the body.
      The detoxification can be slowed in patients carrying the K variant of the
      enzyme. Summarization of literature, discussion on the meaning of BChE in the
      body, and the principles of BChE assay in samples are described in the review
      (Tab. 2, Fig. 8, Ref. 86). Text in PDF www.elis.sk.

PMID- 24329514
TI  - Palliative treatment of the advanced gastric cancer by means of surgery and
      HIPEC.
AB  - OBJECTIVES: We demonstrate a case report of the patient who suffered from
      advanced gastric cancer and was treated by means of surgery and HIPEC.
      BACKGROUND: Gastric cancer is a therapeutic challenge in the European countries
      due to late diagnosis, advanced stages of the disease in time of diagnosis and
      early recurrence in cases where a radical surgery is possible. METHOD: The
      patient with an advanced gastric cancer (pT3N2M1 - peritoneal and ovarian
      metastases) was treated by means of radical surgery in combination with
      hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and early
      postoperative intraperitoneal chemotherapy (EPIC). Surgical treatment was
      followed by a standard chemotherapy. Due to recurrence, there was the second look
      surgery one year later again with HIPEC procedure. RESULTS: Patient survived 32
      months after diagnosis and despite intraperitoneal recurrence she never developed
      clinically significant ascites and she never suffered from intestinal
      obstruction. CONCLUSION: This case demonstrate a potential benefit of new
      oncosurgical approach -radical surgery + HIPEC + EPIC in the treatment of gastric
      cancers (Tab. 2, Fig. 6, Graph 4, Ref. 18). Text in PDF www.elis.sk.

PMID- 24329515
TI  - The role of phosphodiesterase activity on the temperature-dependent responses of
      calf cardiac vein.
AB  - OBJECTIVE: To evaluate the role of phosphodiesterase (PDE) activity in the
      cooling (to 28  degrees C) and warming (41  degrees C)-induced effects of
      carbachol on calf cardiac vein. MATERIAL AND METHODS: Rings obtained from calf
      hearts were suspended in organ baths containing 25 ml of Krebs-Henseleit
      solution, maintained at 37  degrees C, continuously gassed with 95%O2-5%CO2. At
      the end of the resting period the preparations were contracted with carbachol (10
      9-3x10-4M), at 37  degrees C. The same protocol was repeated at 28  degrees C and
      41  degrees C after the preparations were allowed to equilibrate at this
      temperature for 60 min. In order to analyze the role of PDE activity in the
      cooling-and warming-induced vascular response, carbachol (10-9-3x10-4M) was
      applied in the presence of cilostazol (10-6 M), IBMX (10-6 M) and rolipram (10-6
      M), respectively. RESULTS: The sensitivity of carbachol was significantly lower
      during cooling, and higher during warming. Cooling to 28 and warming to 41 
      degrees C, after treatment with IBMX, cilostazol or rolipram, significantly
      decreased the sensitivity to carbachol (p<0.05). CONCLUSION: The results of the
      present study suggest that PDE activity plays an essential role in cooling-and
      warming-induced changes of calf cardiac vein treated with carbachol (Tab. 1, Fig.
      2, Ref. 34). Text in PDF www.elis.sk.

PMID- 24329516
TI  - Capacity building in nutrition science: revisiting the curricula for medical
      professionals.
AB  - The current nutrition education curricula for students in U.S. medical schools,
      and schools of other health professions, such as nursing and oral health, do not
      provide enough opportunity to gain knowledge of the interactions among micro- and
      macronutrients, their role in maintaining optimal body functions, factors that
      interfere with these interactions, or, importantly, how to integrate this
      knowledge into medical practice. There is a need to better prepare healthcare
      professionals for identifying nutrition risk and managing hospitalized patients,
      especially those with chronic conditions, using an interprofessional, team-based
      approach. A major goal of this report is to revisit current nutrition training
      programs for physicians and other healthcare professionals in order to explore
      opportunities for providing healthcare providers with the essential tools of
      preventative and therapeutic nutrition intervention strategies. The issues
      addressed include whether a consensus exists on how to integrate basic and
      applied nutrition into the general healthcare professional curriculum, and if so,
      at which stages of training and at what depth should these integrations occur;
      how nutrition education is dealt with and achieved throughout all the health
      professions; and whether current nutrition education models are sufficient. To
      help address these issues, the report will review current nutrition education
      practices-their strengths and weaknesses-as well as evaluate promising new
      initiatives, and offer proposals for new directions for nutrition education
      training of future generation of medical practitioners. 

PMID- 24329517
TI  - Circadian clocks, brain function, and development.
AB  - Circadian clocks are temporal interfaces that organize biological systems and
      behavior to dynamic external environments. Components of the molecular clock are
      expressed throughout the brain and are centrally poised to play an important role
      in brain function. This paper focuses on key issues concerning the relationship
      among circadian clocks, brain function, and development, and discusses three
      topic areas: (1) sleep and its relationship to the circadian system; (2) systems
      development and psychopathology (spanning the prenatal period through late life);
      and (3) circadian factors and their application to neuropsychiatric disorders. We
      also explore circadian genetics and psychopathology and the selective pressures
      on the evolution of clocks. Last, a lively debate is presented on whether
      circadian factors are central to mood disorders. Emerging from research on
      circadian rhythms is a model of the interaction among genes, sleep, and the
      environment that converges on the circadian clock to influence susceptibility to
      developing psychopathology. This model may lend insight into effective treatments
      for mood disorders and inform development of new interventions. 

PMID- 24329518
TI  - Comment on: advances in primary immunodeficiency diseases in Latin America:
      epidemiology, research, and perspectives. Ann. N.Y. Acad. Sci. 1250: 62-72
      (2012).

PMID- 24329520
TI  - The prevalence of inverse recurrent suppuration: a population-based study of
      possible hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease
      involving inverse recurrent suppuration (IRS). The epidemiology of the disease is
      not well described, with previous studies reporting prevalence estimates from
      0.00033% to 4%. OBJECTIVE: To determine the prevalence of IRS in a large
      population-based survey. METHODS: Data were obtained from a general cross
      sectional population study in Denmark. A validated self-administered
      questionnaire was used to identify IRS. Persons with the combination of outbreaks
      of 'boils' during the last 6 months in predefined areas and a minimum of two
      boils were identified. RESULTS: A total of 16 404 adults aged 30-89 years
      provided data and the overall prevalence of IRS was found to be 2.10% [95%
      confidence interval (CI) 1.88-2.32]; in men it was 1.58% (95% CI 1.29-1.86) and
      in women 2.56% (95% CI 2.21-2.86). No data for adults aged 20-29 years were
      included. The prevalence declined with age. The majority of cases (72.9%) had a
      body mass index of >= 25 kg m(-2) and 77.7% were current or ex-smokers. The mean
      number of inflamed lesions was 6.5 (range 2-67) during the last 6 months. The
      lesions affected mostly the genitalia (43.4%) and groin (39.8%) for women and
      'other places' (not specified) (78.8%) for men. CONCLUSIONS: Data on IRS suggest
      that HS may be more prevalent than previously suggested, and the prevalence may
      be comparable to other major dermatoses, e.g. psoriasis. However, as no physician
      examination was done, the risk of recall and information bias is a major
      limitation.

PMID- 24329521
TI  - Sensory and nutritional quality of white rice after residential storage for up to
      30 years.
AB  - Rice is a staple food that may be packaged for long-term storage to ameliorate
      unpredictable circumstances such as crop failures and natural disasters. The
      sensory and nutritional quality of 18 samples of long grain white rice (11
      regular, 7 parboiled) packaged in cans stored up to 30 years at ambient
      temperature in residential locations was evaluated. Hedonic scores for overall
      liking ranged from 5.6 to 6.6 (9-point scale) and all samples regardless of age
      scored above 5, "neither like nor dislike". All but one 30-year parboiled sample
      were considered acceptable for everyday use by greater than 50% of panelists, and
      for emergency use by over 88% of panelists. Thiamin concentrations ranged from
      0.5 to 3.6 ug/g. Although vitamin stability appears to be limited, rice retains
      much of its sensory quality over time and the presence of minerals and other
      stable macronutrients may justify its inclusion in a long-term food storage
      regimen.

PMID- 24329519
TI  - Identification of plumericin as a potent new inhibitor of the NF-kappaB pathway
      with anti-inflammatory activity in vitro and in vivo.
AB  - BACKGROUND AND PURPOSE: The transcription factor NF-kappaB orchestrates many pro
      inflammatory signals and its inhibition is considered a promising strategy to
      combat inflammation. Here we report the characterization of the natural product
      plumericin as a highly potent inhibitor of the NF-kappaB pathway with a novel
      chemical scaffold, which was isolated via a bioactivity-guided approach, from
      extracts of Himatanthus sucuuba, an Amazonian plant traditionally used to treat
      inflammation-related disorders. EXPERIMENTAL APPROACH: A NF-kappaB luciferase
      reporter gene assay was used to identify NF-kappaB pathway inhibitors from H.
      sucuuba extracts. Monitoring of TNF-alpha-induced expression of the adhesion
      molecules VCAM-1, ICAM-1 and E-selectin by flow cytometry was used to confirm NF
      kappaB inhibition in endothelial cells, and thioglycollate-induced peritonitis in
      mice to confirm effects in vivo. Western blotting and transfection experiments
      were used to investigate the mechanism of action of plumericin. KEY RESULTS:
      Plumericin inhibited NF-kappaB-mediated transactivation of a luciferase reporter
      gene (IC50 1 MUM), abolished TNF-alpha-induced expression of the adhesion
      molecules VCAM-1, ICAM-1 and E-selectin in endothelial cells and suppressed
      thioglycollate-induced peritonitis in mice. Plumericin exerted its NF-kappaB
      pathway inhibitory effect by blocking IkappaB phosphorylation and degradation.
      Plumericin also inhibited NF-kappaB activation induced by transfection with the
      constitutively active catalytic subunit of the IkappaB kinase (IKK-beta),
      suggesting IKK involvement in the inhibitory action of this natural product.
      CONCLUSION AND IMPLICATIONS: Plumericin is a potent inhibitor of NF-kappaB
      pathways with a new chemical scaffold. It could be further explored as a novel
      anti-inflammatory lead compound.

PMID- 24329522
TI  - Parents' dental anxiety and oral health literacy: effects on parents' and
      children's oral health-related experiences.
AB  - OBJECTIVE: To explore a) the relationship between parents'/guardians' dental
      anxiety and oral health literacy and b) those between these variables and
      background and oral health-related characteristics. METHODS: Survey data were
      collected from 187 parents/guardians (81% female; average age 37 years). Dental
      anxiety was measured with the Dental Anxiety Scale - Revised (DAS-R) and oral
      health literacy with the Rapid Estimate of Adult Literacy in Dentistry (REALD
      30). Children's dental charts were reviewed to collect information about their
      dental treatment. RESULTS: DAS-R and REALD-30 scores were correlated (r = -0.22;
      P = 0.003). A multivariate regression model with DAS-R score as the dependent
      variable showed that the DAS-R score has a significant multivariate association
      with REALD-30, oral health, income, and presence of fillings. CONCLUSIONS: Dental
      anxiety and oral health literacy are related. However, DAS score has a
      significant multivariate association with the four variables REALD-30 score, oral
      health, income, and presence of fillings. These findings show that among
      socioeconomically disadvantaged patients, the contributors to poor oral health
      are interrelated and multidetermined and include poor oral health literacy and
      dental anxiety. The public health message is that in order to improve the overall
      oral health of socioeconomically disadvantaged patients, public health
      stakeholders need to consider how to communicate with these patients effectively
      and how to reduce dental anxiety. Gaining a better understanding of how to
      communicate with parents a) at an appropriate literacy level and b) in a way that
      it reduces dental anxiety is therefore crucial.

PMID- 24329523
TI  - Photoacclimation responses of the brown macroalga Sargassum Cymosum to the
      combined influence of UV radiation and salinity: cytochemical and ultrastructural
      organization and photosynthetic performance.
AB  - The photoacclimation responses of the brown macroalga Sargassum cymosum were
      studied to determine its cytochemical and ultrastructural organization, as well
      as photosynthetic pigments and performance. S. cymosum was cultivated in three
      salinities (30, 35 and 40 psu) under four irradiation treatments: PAR-only, PAR +
      UVA, PAR + UVB and PAR + UVA + UVB. Plants were exposed to PAR at 70 MUmol
      photons m(-2) s(-1), PAR + UVB at 0.35 W m(-2) and PAR +UVA at 0.70 W m(-2) for 3
      h per day during 7 days in vitro. Growth rate was not significantly affected by
      any type of radiation or salinity. The amount of pigments in S. cymosum was
      significantly influenced by the interaction of salinity and radiation treatments.
      Compared with PAR-only, UVR treatments modified the kinetics patterns of the
      photosynthesis/irradiance curve. After exposure to UVR, S. cymosum increased cell
      wall thickness and the presence of phenolic compounds. The number of mitochondria
      increased, whereas the number of chloroplasts showed few changes. Although S.
      cymosum showed insensitivity to changes in salinity, it can be concluded that
      samples treated under four irradiation regimes showed structural changes, which
      were more evident, but not severe, under PAR + UVB treatment.

PMID- 24329525
TI  - Time-dependent wave packet approach to quantum reactive scattering.
AB  - The use of wave packets in time-dependent quantum mechanical studies of chemical
      reaction dynamics is examined. The basic priniciples of time-dependent scattering
      theory are reviewed. The Fourier-grid method and various propagation schemes are
      discussed. A number of useful methodologies are examined, such as discrete
      variable representations and close-coupling expansions, multiconfiguration self
      consistent field formulations, and the mixing of classical with quantum
      variables. Numerous applications to gas-surface scattering are considered. The
      dissociative adsorption of diatomic molecules on metal surfaces and the Eley
      Rideal recombination of gas-phase atoms with atoms adsorbed on surfaces are
      discussed in detail. Applications to gas-phase reactions are also examined, with
      emphasis on three-body A+BC and four-body AB+CD reactions. 

PMID- 24329524
TI  - Effect of once-daily insulin detemir on oral antidiabetic drug (OAD) use in
      patients with type 2 diabetes.
AB  - WHAT IS KNOWN AND OBJECTIVE: There are acknowledged benefits to continuing
      metformin when initiating insulin, but there appears to be growing concern over
      the role of sulphonylureas and thiazolidinediones when used in combination with
      insulin. This analysis investigates the effects of continuing or discontinuing
      oral antidiabetic drugs (OADs) following the initiation of once-daily insulin
      detemir. METHODS: SOLVE is a 24-week, multinational observational study of
      insulin detemir initiation in patients with type 2 diabetes mellitus treated with
      one or more OADs. RESULTS: In the total cohort (n = 17 374), there were
      significant improvements in HbA1c (-1.3%, 95% CI -1.34; -1.27%) and weight (-0.6
      kg, 95% CI -0.65; -0.47 kg), with an increase in the incidence rate of minor
      hypoglycaemia (+0.256 events ppy, P < 0.001), but not severe hypoglycaemia (
      0.038 events ppy, P < 0.001). Study participants had information on OAD use
      either prior to (n = 17 086) or during insulin initiation (n = 16 346). HbA1c
      reductions were significantly greater in patients continuing treatment with
      metformin (-1.3% vs. -1.1%, P < 0.01), thiazolidinediones (-1.3% vs. -1.0%, P <
      0.01) and DPP-IV inhibitors (-1.3% vs. -0.9%, P < 0.001). Final insulin doses
      were significantly greater in patients discontinuing treatment with
      sulphonylureas (0.29 vs. 0.26 IU/kg, P < 0.001), glinides (0.28 vs. 0.26 IU/kg, P
      < 0.01), thiazolidinediones (0.31 vs. 0.26 IU/kg, P < 0.001) and DPP-IV
      inhibitors (0.35 vs. 0.29 IU/kg, P < 0.001) compared with patients continuing
      these respective agents. All patient subgroups had a mean weight loss
      irrespective of OAD continuation, apart from those continuing thiazolidinediones
      (+0.2 kg). The largest improvements in weight were seen following the withdrawal
      of sulphonylureas and thiazolidinediones (-1.1 and -1.1 kg, respectively). WHAT
      IS NEW AND CONCLUSION: Discontinuation (or switching) of OADs at the time of
      insulin initiation appears to be governed principally by concerns about
      hypoglycaemia and weight. HbA1c improvements were smaller in patients
      discontinuing OADs at the time of insulin initiation and may be associated with
      insufficient insulin titration.

PMID- 24329526
TI  - The TCR gammadelta repertoire and relative gene expression characteristics of T
      ALL cases with biclonal malignant Vdelta1 and Vdelta2 T cells.
AB  - Despite significant improvement in our understanding of T-cell acute
      lymphoblastic leukemia (T-ALL) biology and pathogenesis, many questions remain
      unanswered. In previous studies, we found a T-ALL case with two malignant T-cell
      clones with Vdelta1Ddelta2Ddelta3Jdelta1 and Vdelta2Ddelta3Jdelta2
      rearrangements. In this study, we further characterized T-ALL cases with two
      malignant clones containing Vdelta1Ddelta3Jdelta1 and Vdelta2Ddelta1Jdelta1
      rearrangements using fine-tiling array comparative genomic hybridization,
      ligation-mediated polymerase chain reaction (LM-PCR), sequencing, and reverse
      transcription polymerase chain reaction (RT-PCR) analysis. We further analyzed
      the distribution and clonality of the T-cell receptor (TCR) Vgamma and Vdelta
      subfamily T cells in the two T-ALL cases by RT-PCR and GeneScan. Monoclonal
      Vdelta1 and Vdelta2 subfamilies were confirmed in both samples, the Vdelta3
      through Vdelta7 subfamilies could not be detected in the T-ALL samples, whereas
      the oligoclonal Vdelta8 subfamily could be identified. Based on the clinical
      finding that both of the T-ALL cases with two malignant T-cell clones had a poor
      outcome, we attempted to compare the expression pattern of genes related to T
      cell activation and proliferation between cases with the malignant Vdelta1 and
      Vdelta2 T-cell clones and T-ALL cases with a mono-malignant Valpha T-cell clone.
      We selected two T-ALL cases with ValphaJalpha rearrangements and analyzed the
      expression level of Notch1, TAL1, and the CARMA-BCL10-MALT-A20-NF-kappaB pathway
      genes by real-time PCR. A20 had significantly higher expression in the biclonal
      compared with the monoclonal T-ALL group (p=0.0354), and there was a trend toward
      higher expression for the other genes in the biclonal group with the exception of
      TAL1, although the differences were not statistically significant. In conclusion,
      we identified two T-ALL cases with biclonal malignant T-cell clones and described
      the characteristics of the biclonal T-ALL subtype and its gene expression
      pattern. Thus, our findings may improve the understanding of biclonal T-ALL. 

PMID- 24329528
TI  - Epigenetics in the cerebrovascular system: changing the code without altering the
      sequence.

PMID- 24329527
TI  - Evaluation of all nonsynonymous single-nucleotide polymorphisms in the gene
      encoding human deoxyribonuclease I-like 1, possibly implicated in the blocking of
      endocytosis-mediated foreign gene transfer.
AB  - Many nonsynonymous single-nucleotide polymorphisms (SNPs) in the human
      deoxyribonuclease I-like 1 (DNase 1L1) gene, possibly implicated in the blocking
      of endocytosis-mediated foreign gene transfer, have been identified, but only
      limited population data are available and no studies have evaluated whether such
      SNPs are functional. Genotyping of all 21 nonsynonymous human DNase 1L1 SNPs was
      performed in 16 different populations representing three ethnic groups using the
      PCR-restriction fragment length polymorphism technique. All of the nonsynonymous
      SNPs, except for SNP p.Val122Ile in Caucasian populations, exhibited a
      monoallelic distribution in all of the populations. On the basis of alterations
      in the activity levels resulting from the corresponding amino acid substitutions,
      two activity-abolishing and four activity-reducing SNPs were confirmed to be
      functional. Although all of the nonsynonymous SNPs that affected the catalytic
      activity showed extremely low genetic heterogeneity, it seems plausible that a
      minor allele of six SNPs producing a loss-of-function or extremely low-activity
      variant could serve directly as a genetic risk factor for diseases. Especially,
      the amino acid residues in activity-abolishing SNPs were conserved in animal
      DNases 1L1. Furthermore, results of phylogenetic analysis suggest that DNase 1L1
      might have appeared latest among the DNase I family during the course of
      molecular evolution. 

PMID- 24329529
TI  - In vitro study of cypermethrin on human spermatozoa and the possible protective
      role of vitamins C and E.
AB  - Cypermethrin, a type II synthetic pyrethroid pesticide, is widely used in pest
      control programmes in agriculture and public health. This study aimed to assess
      the potential effect of cypermethrin on human spermatozoa and the possible
      ameliorative effects of vitamins C and E. Semen samples of 20 healthy
      normozoospermic men were divided into six aliquots at room temperature. The first
      aliquot served as control not exposed to treatments, and the second was incubated
      with 20 mm vit. C and 2 mm vit. E where the third one was exposed to 10 MUm
      cypermethrin for 6 h. The other three aliquots were incubated with vit. C, vit. E
      and both vitamins for 30 min before cypermethrin exposure. Semen aliquots were
      analysed for sperm motility, sperm viability, hypo-osmotic swelling test and
      modified alkaline comet assay. The results demonstrated a significant decrease in
      sperm motion, sperm function and increased sperm DNA damage in the cypermethrin
      group. Addition of vitamins C and E alone/combined led to significant improvement
      in sperm motion, sperm function and DNA damage, being maximal with both vitamins
      together. It is concluded that in vitro cypermethrin can alter sperm function and
      induce DNA damage in spermatozoa, which is improved after using vitamins C and E.

PMID- 24329530
TI  - Breath testing as a method for detecting lung cancer.
AB  - Early diagnosis of lung cancer is important due to high mortality in late stages
      of the disease. An ideal approach for population screening could be the breath
      analysis, due to its non-invasiveness, simplicity and cheapness. Using sensitive
      methods of analysis like gas chromatography/mass spectrometry in exhaled air of
      cancer patients were discovered some volatile organic compounds - possible
      candidates for cancer markers. However, these compounds were not specific for
      cancer cells. At the same time, integrative approaches used to analyze the
      exhaled breath have demonstrated high sensitivity and specificity of this method
      for lung cancer diagnosis. Such integrative approaches include detection of smell
      prints by electronic nose or integrated analysis of wide range of volatile
      organic compounds detected by gas chromatography/mass spectrometry or related
      methods. Modern statistical pattern recognition systems like logistic regression
      analysis, support vector machine or analysis by artificial neuronal network may
      improve diagnostic accuracy.

PMID- 24329532
TI  - Association of peroxisome proliferator-activated receptor gamma Pro12Ala gene
      polymorphism with type 2 diabetic nephropathy risk in Caucasian population.
AB  - Association of peroxisome proliferator-activated receptor gamma (PPARgamma)
      Pro12Ala gene polymorphism with type 2 diabetic nephropathy (T2DN) risk in
      Caucasians is still not clear. This investigation was conducted to assess if
      there was an association between the PPARgamma Pro12Ala gene polymorphism and
      T2DN risk in Caucasians using meta-analysis. The relevant literatures were
      identified from PubMed, and Cochrane Library on 10 October 2013, and eligible
      studies were included and synthesized. Six reports including eight studies were
      recruited into this meta-analysis for the association of the PPARgamma Pro12Ala
      gene polymorphism with T2DN risk in Caucasians. The Pro/Pro genotype was shown to
      be associated with T2DN risk in Caucasians. However, the Ala/Ala genotype and Ala
      allele were not associated with T2DN risk in Caucasians. In the sensitivity
      analysis, according to the control source from hospital, the control source from
      population, the genotyping methods using PCR-RFLP, Taqman, sample size of case
      <100, the association of the PPARgamma Pro12Ala gene polymorphism with T2DN risk
      was similar to those in non-sensitivity analysis. In conclusion, the PPARgamma
      Pro/Pro genotype was associated with T2DN risk in Caucasians, but the Ala/Ala
      genotype and Ala allele not. However, additional studies are required to firmly
      establish a correlation between the PPARgamma Pro12Ala gene polymorphism and T2DN
      risk in Caucasians.

PMID- 24329533
TI  - In silico evaluation for the potential naturally available drugs for breast
      cancer.
AB  - Breast cancer is one of the major causes of deaths in women. During the incidence
      of breast cancer, the HER-2 is amplified and over expressed. This transmembrane
      receptor is involved in the signal transduction pathway. The present article
      evaluates 14 naturally available breast cancer drugs, in silico and the ADMET
      studies were conducted. The HER-2, a validate breast cancer target was taken for
      the present study. The protein was prepared for docking on the Discovery Studio
      2.5. About 14 ligand molecules were used to dock with HER-2 after they were
      prepared for docking. The ADMET assessment was also done. The dock results showed
      that the ligand 4'-epidoxorubicin to be the potential drug with the highest dock
      score of 49.386. Among the 14 naturally available breast cancer drugs, our
      results evaluated that 4'-epidoxorubicin as the best drug for breast cancer.
      Further, the ADMET studies give an idea about the drug molecules.

PMID- 24329534
TI  - Evaluation of the European tick-borne encephalitis vaccine against Omsk
      hemorrhagic fever virus.
AB  - This study focused on the antigenic cross-reactivity between tick-borne
      encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) to assess the
      efficacy of the commercial TBE vaccine against OHFV infection. Neutralization
      tests performed on sera from OHFV- and TBEV-infected mice showed that
      neutralizing antibodies are cross-protective. The geometric mean titers of
      antibodies against TBEV and OHFV from TBEV-infected mice were similar. However,
      the titers of anti-TBEV antibodies in OHFV-infected mice were significantly lower
      than those of anti-OHFV antibodies in the same animals. In mouse vaccination and
      challenge tests, the TBE vaccine provided 100% protection against OHFV infection.
      Eighty-six percent of vaccinees seroconverted against OHFV following complete
      vaccination, and the geometric mean titers of neutralizing antibodies against
      OHFV were comparable to those against TBEV. These data suggest that the TBE
      vaccine can prevent OHFV infection. 

PMID- 24329536
TI  - Experience and guidelines.

PMID- 24329535
TI  - Inflammation in neurodegenerative diseases--an update.
AB  - Neurodegeneration, the progressive dysfunction and loss of neurons in the central
      nervous system (CNS), is the major cause of cognitive and motor dysfunction.
      While neuronal degeneration is well-known in Alzheimer's and Parkinson's
      diseases, it is also observed in neurotrophic infections, traumatic brain and
      spinal cord injury, stroke, neoplastic disorders, prion diseases, multiple
      sclerosis and amyotrophic lateral sclerosis, as well as neuropsychiatric
      disorders and genetic disorders. A common link between these diseases is chronic
      activation of innate immune responses including those mediated by microglia, the
      resident CNS macrophages. Such activation can trigger neurotoxic pathways leading
      to progressive degeneration. Yet, microglia are also crucial for controlling
      inflammatory processes, and repair and regeneration. The adaptive immune response
      is implicated in neurodegenerative diseases contributing to tissue damage, but
      also plays important roles in resolving inflammation and mediating
      neuroprotection and repair. The growing awareness that the immune system is
      inextricably involved in mediating damage as well as regeneration and repair in
      neurodegenerative disorders, has prompted novel approaches to modulate the immune
      system, although it remains whether these approaches can be used in humans.
      Additional factors in humans include ageing and exposure to environmental factors
      such as systemic infections that provide additional clues that may be human
      specific and therefore difficult to translate from animal models. Nevertheless, a
      better understanding of how immune responses are involved in neuronal damage and
      regeneration, as reviewed here, will be essential to develop effective therapies
      to improve quality of life, and mitigate the personal, economic and social impact
      of these diseases. 

PMID- 24329537
TI  - Functional characterization of the two ferrochelatases in Arabidopsis thaliana.
AB  - The enzyme ferrochelatase catalyses the formation of protoheme by inserting
      Fe(2+) into protoporphyrin IX. Although most organisms express only one
      ferrochelatase, all land plants analysed so far possess at least two
      ferrochelatase proteins. Analysis of publicly available expression data suggests
      that the two Arabidopsis thaliana ferrochelatases, FC1 and FC2, serve different
      functions, corroborating previous assumptions. Co-expression analysis of FC1 and
      FC2, together with microarray analyses, implies that fc1 and fc2 trigger
      different modes of plastid signalling in roots and leaves, respectively, and
      indicates that FC2 might be involved in stress responses. Thus, loss of FC2
      increases resistance to salt and flagellin treatment. Whereas fc1 plants showed
      no obvious mutant phenotype, fc2 mutants formed abnormally small, pale green
      rosette leaves; were low in chlorophylls, carotenoids and several photosynthetic
      proteins; and their photosynthetic performance was impaired. These phenotypes are
      attenuated by growth in continuous light, in agreement with the finding that fc2
      plants accumulate protochlorophyllide and display a fluorescent (flu) phenotype
      in the dark. In consequence we show that, contrary to earlier suggestions, FC2
      produces heme not only for photosynthetic cytochromes, but also for proteins
      involved in stress responses, whereas the impairment of FC1 apparently interferes
      only marginally with stress responses. 

PMID- 24329538
TI  - Is there a need for smooth muscle cell transplantation in urethral
      reconstruction?
AB  - BACKGROUND: Hypospadias and urethral strictures are conditions requiring
      additional tissue for reconstruction. Due to a limited source of tissue,
      autologous skin and oral mucosa are frequently used. However, long-term follow-up
      studies demonstrated significant complications and diminished quality of life.
      Recently, a variety of tubular biodegradable biomaterials have been used. Cell
      seeding seems to be important to improve the host acceptance and
      neovascularization. OBJECTIVE: To compare in vivo performance of smooth muscle
      cell (SMC)-seeded and unseeded tubular collagen-based scaffolds in a rabbit
      urethral reconstruction model. MATERIALS AND METHODS: Sixteen New Zealand rabbits
      underwent an open-bladder biopsy for SMC harvesting. The SMCs were cultured for 3
      weeks and labeled with ethynyldeoxyuridine (EdU). A 1-cm-length tubular collagen
      based 0.5 wt% scaffold was seeded and cultured with SMCs and implantation in a
      rabbit model. Eight rabbits received SMC-seeded scaffolds for a 1-cm-length
      circumferential urethral repair, situated 1.5 cm from the meatus. After 1 and 3
      months, four rabbits underwent a urethrography and were sacrificed. The penises
      underwent hematoxylin and eosin, immunohistochemistry, and EdU fluorescence
      staining. In the control group eight rabbits received acellular scaffolds.
      RESULTS: The SMC-seeded group presented one stricture at 1 month and one fistula
      at 3 months. Three strictures were present in the unseeded group at 1 month and
      one at 3 months. In the seeded group, more SMC expression and neovascularization
      was observed, and less mononuclear and giant cells could be found. All scaffolds
      showed luminal urothelial cell revetment. The detection of EdU-labeled SMCs
      revealed SMC transplantation survival. CONCLUSION: SMC-seeded tubular collagen
      scaffolds improved urethral regeneration in this rabbit model. Such constructs
      may be valuable for repair of severe urethral diseases.

PMID- 24329541
TI  - Inhibition of proinflammatory cytokine by IL-25 in Vogt-Koyanagi-Harada syndrome.
AB  - PURPOSE: Vogt-Koyanagi-Harada (VKH) syndrome is a multisystem disorder presumed
      to be mediated by an autoimmune response. Recent studies have shown that
      interleukin (IL) 25 was involved in the T-cell immune response. This study
      analyzed the expression and potential role of IL-25 in the pathogenesis of VKH
      syndrome. METHODS: The IL-25 serum levels were determined by enzyme-linked
      immunosorbent assay (ELISA). The IL-1beta, IL-6, and TNF-alpha level in
      supernatants of PBMCs cultured with LPS in the absence or presence of
      recombinant(r) IL-25 was detected by ELISA. RESULTS: A significantly decreased
      serum IL-25 level was found in VKH patients. In vitro experiments showed that rIL
      25 was able to significantly inhibit the production of IL-1beta, IL-6, and TNF
      alpha by PBMCs from active VKH patients. CONCLUSIONS: IL-25 may be involved in
      the development of VKH syndrome, possibly by inhibiting the expression of
      proinflammatory cytokines.

PMID- 24329542
TI  - Same-sex sexual relationships in the national social life, health and aging
      project: making a case for data collection.
AB  - This study describes the previously unexplored subsample of respondents who
      reported at least 1 same-sex sexual relationship (SSSR) in the National Social
      Life, Health, and Aging Project (NSHAP). The NSHAP collected data from 3,005
      adults (aged 57-85). Approximately 4% (n = 102) of respondents reported at least
      one SSSR. These sexual minority elders were younger, more educated, were more
      likely to be working, had fewer social supports, and better physical health.
      Results may indicate crisis competence in sexual minority elders. Collecting
      sexual orientation and gender identity data in larger, US-based probability
      samples would inform the development of appropriate community-based services and
      supports. 

PMID- 24329543
TI  - Asenapine treatment and health-related quality of life in patients experiencing
      bipolar I disorder with mixed episodes: post-hoc analyses of pivotal trials.
AB  - OBJECTIVE: To evaluate the baseline impact of episode type (manic vs. mixed),
      defined using DSM-IV-TR criteria, in bipolar I disorder (BD-I) on health-related
      quality of life (HRQoL), and to investigate the differential effect of asenapine
      vs. placebo and olanzapine on HRQoL in BD-I patients with mixed episodes.
      METHODS: In two identically designed 3 week, randomized, double-blind, flexible
      dose, placebo- and olanzapine-controlled trials of asenapine, HRQoL was assessed
      using the 36-item Short-Form Health Survey (SF-36v2) administered at baseline and
      endpoint. In addition to evaluating the impact of clinical presentation (manic
      vs. mixed episodes) on baseline HRQoL, the impact of treatment intervention on
      HRQoL was assessed via analysis of covariance models at study endpoint, with
      center and treatment-by-diagnosis interaction as fixed effect and baseline score
      as covariates. RESULTS: A total of 960 BD-I patients (asenapine: 372; olanzapine:
      391; placebo: 197) were included in the two studies. The observed burden of
      disease on HRQoL was substantial compared to general US population norms,
      particularly in patients experiencing mixed episodes. The greatest impairments
      were observed in the mental domains of HRQoL (Mental Component Summary scores:
      mixed = 31.9; manic = 42.8). For patients with mixed episodes, when compared to
      olanzapine, asenapine treatment was associated with improvements noted in every
      domain, which did not reach statistical significance except for Vitality
      (asenapine = 55.0, olanzapine = 51.3; p = 0.014) and Role-Emotional (asenapine =
      44.8, olanzapine = 40.3; p = 0.020). Compared to placebo patients with mixed
      episodes, asenapine treatment provided significant improvements (p < 0.05) in
      Bodily Pain (asenapine = 50.9, placebo = 45.9), Social Functioning (asenapine =
      44.1, placebo = 39.6) and Mental Health (asenapine = 46.6, placebo = 42.7) by
      Week 3; by comparison, olanzapine treatment did not lead to significant
      improvements in any domain of HRQoL compared to placebo. CONCLUSIONS: Post-hoc
      analyses of two trials showed that BD-I patients with mixed episodes reported
      considerable impairments in HRQoL compared to patients with manic episodes. At 3
      weeks, in patients with mixed episodes, asenapine was shown to lead to
      significant improvements in HRQoL compared to olanzapine and placebo. Results
      from these post-hoc analyses should be confirmed in prospective studies. TRIAL
      REGISTRATION: NCT00159744, NCT00159796.

PMID- 24329545
TI  - Research in electrical stimulation fundamentals.

PMID- 24329546
TI  - Impact of polymethylpentene oxygenators on outcomes of all extracorporeal life
      support patients in the United States.

PMID- 24329544
TI  - The contribution of VEGF signalling to fostamatinib-induced blood pressure
      elevation.
AB  - BACKGROUND AND PURPOSE: Fostamatinib is an inhibitor of spleen tyrosine kinase
      (TK). In patients, fostamatinib treatment was associated with increased BP. Some
      TK inhibitors cause BP elevation, by inhibiting the VEGF receptor 2 (VEGFR2).
      Here, we have assessed the mechanistic link between fostamatinib-induced BP
      elevation and inhibition of VEGF signalling. EXPERIMENTAL APPROACH: We used
      conscious rats with automated blood sampling and radio telemetry and
      anaesthetized rats to measure cardiovascular changes. Rat isolated aorta and
      isolated hearts, and human resistance vessels in vitro were also used. NO
      production by human microvascular endothelial cells was measured with the NO
      dependent probe, DAF-FM and VEGFR2 phosphorylation was determined in mouse lung,
      ex vivo. KEY RESULTS: In conscious rats, fostamatinib dose-dependently increased
      BP. The time course of the BP effect correlated closely with the plasma
      concentrations of R406 (the active metabolite of fostamatinib). In anaesthetized
      rats, infusion of R406 increased BP and decreased femoral arterial conductance.
      Endothelial function was unaffected, as infusion of R406 did not inhibit
      hyperaemia- or ACh-induced vasodilatation in rats. R406 did not affect
      contraction of isolated blood vessels. R406 inhibited VEGF-stimulated NO
      production from human endothelial cells in vitro, and treatment with R406
      inhibited VEGFR2 phosphorylation in vivo. R406 inhibited VEGF-induced hypotension
      in anaesthetized rats. CONCLUSIONS AND IMPLICATIONS: Increased vascular
      resistance, secondary to reduced VEGF-induced NO release from endothelium, may
      contribute to BP increases observed with fostamatanib. This is consistent with
      the elevated BP induced by other drugs inhibiting VEGF signalling, although the
      contribution of other mechanisms cannot be excluded.

PMID- 24329547
TI  - Omental flap for treatment of mediastinitis post-left ventricular assist device
      implantation.

PMID- 24329551
TI  - Combination chemotherapy for metastatic extramammary Paget disease.
AB  - BACKGROUND: It is difficult to treat patients in the advanced stages of
      extramammary Paget disease (EMPD) because no effective treatment has yet been
      established. OBJECTIVE: To describe the experience of using combination
      chemotherapy (FECOM) in patients with metastatic EMPD. METHODS: Since we reported
      a case of metastatic EMPD that responded to FECOM, we have treated further
      patients with metastatic EMPD using FECOM at the National Cancer Center Hospital
      in Japan. FECOM consists of epirubicin 40 mg m(-2) , mitomycin C 3.5 mg m(-2) and
      vincristine 0.7 mg m(-2) on day 1, carboplatin 300 mg m(-2) on day 2 and 5
      fluorouracil 350 mg m(-2) on days 2-6. To evaluate the efficacy of this
      combination therapy in patients with metastatic EMPD, data regarding patients
      given FECOM for the first-line treatment of metastatic EMPD were extracted
      retrospectively. RESULTS: Seven patients were eligible for this study. A partial
      response was noted in four evaluable patients (100%). The other three patients
      were not evaluable for clinical response. One of the three unevaluable patients
      showed a decrease in tumour size by 100%, the other two by about 20%. The median
      overall survival and progression-free survival were 9.4 months (7.6-17.3) and 6.5
      months (2.6-7.9), respectively. The 1-year survival rate was 43% (three of
      seven). Three of the seven patients (43%) had grade 3 haematological toxicities.
      All treatment-related toxicities were reversible and there was no febrile
      neutropenia or treatment-related deaths. CONCLUSION: This study suggests that the
      combination chemotherapy FECOM may be a treatment option for patients with
      metastatic EMPD.

PMID- 24329552
TI  - Bioavailability of iron, zinc, folic acid, and vitamin A from fortified maize.
AB  - Several strategies appear suitable to improve iron and zinc bioavailability from
      fortified maize, and fortification per se will increase the intake of
      bioavailable iron and zinc. Corn masa flour or whole maize should be fortified
      with sodium iron ethylenediaminetetraacetate (NaFeEDTA), ferrous fumarate, or
      ferrous sulfate, and degermed corn flour should be fortified with ferrous sulfate
      or ferrous fumarate. The choice of zinc fortificant appears to have a limited
      impact on zinc bioavailability. Phytic acid is a major inhibitor of both iron and
      zinc absorption. Degermination at the mill will reduce phytic acid content, and
      degermed maize appears to be a suitable vehicle for iron and zinc fortification.
      Enzymatic phytate degradation may be a suitable home-based technique to enhance
      the bioavailability of iron and zinc from fortified maize. Bioavailability
      experiments with low phytic acid-containing maize varieties have suggested an
      improved zinc bioavailability compared to wild-type counterparts. The
      bioavailability of folic acid from maize porridge was reported to be slightly
      higher than from baked wheat bread. The bioavailability of vitamin A provided as
      encapsulated retinyl esters is generally high and is typically not strongly
      influenced by the food matrix, but has not been fully investigated in maize. 

PMID- 24329550
TI  - Role of prostaglandin D2 /CRTH2 pathway on asthma exacerbation induced by
      Aspergillus fumigatus.
AB  - Aspergillus fumigatus is often associated in asthmatic patients with the
      exacerbation of asthma symptoms. The pathomechanism of this phenomenon has not
      been fully understood. Here, we evaluated the immunological mechanisms and the
      role of the prostaglandin D2 / Chemoattractant Receptor-Homologous Molecule
      Expressed on Th2 Cells (CRTH2) pathway in the development of Aspergillus
      associated asthma exacerbation. We studied the effects of A. fumigatus on airway
      inflammation and bronchial hyper-responsiveness in a rat model of chronic asthma.
      Inhalation delivery of A. fumigatus conidia increased the airway eosinophilia and
      bronchial hyper-responsiveness in ovalbumin-sensitized, challenged rats. These
      changes were associated with prostaglandin D2 synthesis and CRTH2 expression in
      the lungs. Direct inflammation occurred in ovalbumin-sensitized, challenged
      animals, whereas pre-treatment with an antagonist against CRTH2 nearly completely
      eliminated the A. fumigatus-induced worsening of airway eosinophilia and
      bronchial hyper-responsiveness. Our data demonstrate that production of
      prostaglandin D2 followed by eosinophil recruitment into the airways via a CRTH2
      receptor are the major pathogenic factors responsible for the A. fumigatus
      induced enhancement of airway inflammation and responsiveness. 

PMID- 24329554
TI  - Photochemical generation of 9H-fluorenyl radicals.
AB  - A series of 9-substituted fluorenols and 9,9'-disubstituted-9,9'-bifluorenyls
      were irradiated to give products derived from fluorenyl radicals. Product
      distribution was solvent dependent. A TEMPO adduct was isolated from the
      photoexcitation of 9-fluorenol. An unusual unsymmetrical 3,9'-bifluorenyl was
      observed from the photolysis of 9-trifluoromethylfluorenol and 9,9'
      di(trifluoromethyl)-9,9'-bifluorenyl in more polar or hydrogen-bonding solvents.
      The electronic nature of 9-substituted fluorenyl radicals was probed using
      theoretical calculations showing the dipolar character of species with electron
      deficient groups. These constitute the first examples of "doubly destabilized"
      radicals. 

PMID- 24329555
TI  - Axin expression delays herpes simplex virus-induced autophagy and enhances viral
      replication in L929 cells.
AB  - Axin, a negative regulator of the Wnt signaling pathway, plays a critical role in
      various cellular events including cell proliferation and cell death. Axin
      regulated cell death affects multiple processes, including viral replication. For
      example, axin expression suppresses herpes simplex virus (HSV)-induced necrotic
      cell death and enhances viral replication. Based on these observations, this
      study investigated the involvement of autophagy in regulation of HSV replication
      and found axin expression inhibits autophagy-mediated suppression of viral
      replication in L929 cells. HSV infection induced autophagy in a time- and viral
      dose-dependent manner in control L929 cells (L-EV), whereas virus-induced
      autophagy was delayed in axin-expressing L929 cells (L-axin). Subsequent analysis
      showed that induction of autophagy by rapamycin reduced HSV replication, and that
      inhibiting autophagy by 3-methyladenine (3MA) and beclin-1 knockdown facilitated
      viral replication in L-EV cells. In addition, preventing autophagy with 3MA
      suppressed virus-induced cytotoxicity in L-EV cells. In contrast, HSV replication
      in L-axin cells was resistant to changes in autophagy. These results suggest that
      axin expression may render L929 cells resistant to HSV-infection induced
      autophagy, leading to enhanced viral replication. 

PMID- 24329556
TI  - Prescribing for off-label use and unauthorized medicines in three paediatric
      wards in Finland, the status before and after the European Union Paediatric
      Regulation.
AB  - WHAT IS KNOWN AND OBJECTIVE: The European Paediatric Regulation aims to reduce
      off-label use of medicines in paediatric pharmacotherapy. Prescribing for off
      label use and unauthorized medicines was common in the paediatric wards of the
      Kuopio University Hospital in 2001. To evaluate the possible impact of the
      Regulation on the prevalence and the frequency on such prescribing, we repeated
      the study in 2011 as it was conducted 10 years earlier. METHODS: In this
      prospective study, the prescriptions for patients below 18 years of age were
      reviewed during a 2-week period in each of the three wards; neonatal intensive
      care unit, general paediatric ward and paediatric surgical ward in April and May
      2011. The medicine's authorizing status of all prescriptions was determined
      according to the approved summary of product characteristics valid during the
      study in Finland. Data concerning unauthorized medicines were also recorded and
      classified. RESULTS: Out of the entire study population of 123 patients, 119
      received a total of 1054 prescriptions in 2011. The proportion of patients with
      at least one prescription for off-label use or for an unauthorized medicine was
      significantly higher, 79% (n = 97) in 2011, compared to 58% in 2001 (P < 0.001).
      For newborns, significantly more prescriptions were for off-label use in 2011
      than in 2001 (51% vs. 22%; P < 0.001). The proportion of prescriptions for
      unauthorized medicines was significantly higher in children below 2 years of age
      than in older children in both years (21% vs. 5% in 2011 and 24% vs. 3% in 2001,
      P < 0.001). WHAT IS NEW AND CONCLUSION: The prescribing for off-label use and
      unauthorized medicines was more prevalent in 2011 than in 2001. This indicates
      that the recent legislation has had only minor or no impact on the authorizing
      status of medicines commonly used in paediatric inpatients in specialized care.

PMID- 24329557
TI  - Generation of chimeric piglets by injection of embryonic germ cells from inbred
      Wuzhishan miniature pigs into blastocysts.
AB  - BACKGROUND: Human embryonic stem/germ (ES/EG) cell research poses ethical
      dilemma, it is therefore critical to establish alternative sources of cells for
      relevant studies. Considering the similarities between the inbred miniature
      Wuzhishan pigs (WZSP) and humans, ES/EG from these pigs can serve as potential
      substitutes in human research. In this study, we reported our results that
      successfully established stable EG cell lines from the WZSP. METHODS: Primordial
      germ cells (PGCs) were isolated from the genital ridges of pig fetuses at 25 to
      28 days of pregnancy. To obtain stable EG cell line, PGCs were maintained on STO
      cells in DMEM containing multiple essential growth factors. RESULTS: Two EG cell
      lines were established and characterized by positive alkaline phosphatase
      staining (AKP), expressions of Oct-4, SSEA-1, SSEA-3, SSEA-4, ability to
      differentiate into cells of all three germ layers in vitro, and generation of
      chimeric offsprings after microinjection and embryo transfer. Transmission
      electron microscopy demonstrated that the cytoplasmic structure of pig EG cells
      were rather simple and had a higher nuclear-to-cytoplasm ratio. Scanning electron
      microscopy showed the sizes of pig EG cells were similar to mouse EG cells. Both
      EG cell lines showed normal karyotypes. The EG cells were propagated for more
      than 20 passages and underwent multiple cycles of freezing and thawing, without
      losing their pluripotency (as distinguished by AKP staining). CONCLUSIONS: Both
      in vitro and in vivo evidence strongly demonstrated that EG cells harvested from
      the inbred miniature WZSP were pluripotent and can be used for relevant pig or
      human studies.

PMID- 24329558
TI  - Primary refractory T-cell prolymphocytic leukaemia treated with daily
      administration of Alemtuzumab plus high-dose methylprednisolone.

PMID- 24329559
TI  - Formulation of nanoemulsion: a comparison between phase inversion composition
      method and high-pressure homogenization method.
AB  - There is lot of confusion in the literatures regarding the method of production
      of nanoemulsion. According to some authors, only the methods using high energy
      like high-pressure microfluidizer or high-frequency ultra-sonic devices can
      produce actual nanoemulsions. In contrast to this concept, one research group
      reported for the first time the preparation of nanoemulsion by a low-energy
      method. Later on many authors reported about the low-energy emulsification
      method. The purpose of this work is to formulate, evaluate and compare
      nanoemulsions prepared using high-energy as well as low-energy method.
      Nanoemulsions formulated were based on the phase inversion composition technique
      (low energy method) and were selected from the ternary phase diagram based on the
      criterion of their being a minimum concentration of S(mix) used in the
      formulation. For high-pressure homogenization method (high energy method) Design
      Expert software was used, and the desirability function was probed to acquire an
      optimized formulation. No significant difference (p > 0.05) was observed in the
      globule size of formulations made by each method, but the value of poly
      dispersibility index between the two methods was found to be extremely
      significant (p < 0.001). A very significant difference (p < 0.001) was observed
      in the drug release from formulations made by each method. More than 60% of the
      drug was released from all the formulations in the initial 2 h of the dissolution
      study.

PMID- 24329560
TI  - Cutaneous melanoma in patients treated with tumour necrosis factor inhibitors: a
      retrospective series of 15 patients.
AB  - BACKGROUND: Several case reports suggested that tumour necrosis factor-alpha
      (TNF) inhibitors might increase the incidence and/or alter the natural course of
      melanoma towards a more aggressive behaviour. OBJECTIVE: Our objective was to
      point if history of melanoma in patients exposed to TNF inhibitors could present
      with a particular pattern at diagnosis or during follow-up. METHODS: We performed
      a retrospective multicentre study settled in the West part of France to collect
      and analyse all cases of patients with melanoma who received anti-TNF therapy.
      RESULTS: Fifteen cases were included. First, 10 patients (mean age: 55.6 years;
      sex ratio: 1) had a melanoma diagnosed after TNF inhibitors initiation. The mean
      duration between initiation of treatment and melanoma was 48.7 months. Two
      patients died of metastatic disease. Second, four patients had a past history of
      melanoma before anti-TNF therapy (mean duration of treatment: 10.8 months). None
      experienced a progression of melanoma disease. Last, one woman had a past history
      of melanoma before and then developed a second melanoma when exposed to
      biotherapy. CONCLUSION: Our case series does not reveal a distinct profile of
      melanoma in the patients exposed to TNF inhibitors. Additional prospective trials
      including larger number of patient are needed to demonstrate the possible link
      between biological therapy with TNF inhibitors and development of melanoma.

PMID- 24329561
TI  - Validity and agreement of uveitis experts in interpretation of ocular photographs
      for diagnosis of Behcet uveitis.
AB  - Abstract Purpose: To evaluate agreement and estimate sensitivity and specificity
      of uveitis specialists' interpretation of ocular photographs in diagnosing Behcet
      uveitis. METHODS: Fourteen Turkish uveitis specialists, masked to demographic and
      clinical features of patients, independently labeled ocular photographs (29
      Behcet/30 other diagnoses) as "Behcet uveitis" or "non-Behcet." Level of
      agreement was evaluated using kappa statistics. Photographs were categorized
      based on ocular signs captured and performance of observers. RESULTS: Exact
      agreement with the correct diagnosis was 56-81%. Seven reviewers correctly
      labeled more than 70% of photographs. Interobserver agreement among those 7
      reviewers revealed moderate (kappa = 0.41-0.60) or substantial (kappa = 0.61
      0.80) agreement in 76% of pairs. Smooth layered hypopyon, superficial retinal
      infiltrate with retinal hemorrhages, and branch retinal vein occlusion with
      vitreous haze were correctly recognized as Behcet uveitis by majority of
      reviewers. CONCLUSIONS: There are ocular signs of Behcet disease that can be
      considered diagnostic even in the absence of any other clinical information.

PMID- 24329562
TI  - Vitamin B12 regulates photosystem gene expression via the CrtJ antirepressor AerR
      in Rhodobacter capsulatus.
AB  - The tetrapyrroles haem, bacteriochlorophyll and cobalamin (B12 ) exhibit a
      complex interrelationship regarding their synthesis. In this study, we
      demonstrate that AerR functions as an antirepressor of the tetrapyrrole regulator
      CrtJ. We show that purified AerR contains B12 that is bound to a conserved
      histidine (His145) in AerR. The interaction of AerR to CrtJ was further
      demonstrated in vitro by pull down experiments using AerR as bait and quantified
      using microscale thermophoresis. DNase I DNA footprint assays show that AerR
      containing B12 inhibits CrtJ binding to the bchC promoter. We further show that
      bchC expression is greatly repressed in a B12 auxotroph of Rhodobacter capsulatus
      and that B12 regulation of gene expression is mediated by AerR's ability to
      function as an antirepressor of CrtJ. This study thus provides a mechanism for
      how the essential tetrapyrrole, cobalamin controls the synthesis of
      bacteriochlorophyll, an essential component of the photosystem. 

PMID- 24329564
TI  - Role of angiotensin-converting enzyme 2 (ACE2) in diabetic cardiovascular
      complications.
AB  - Diabetes mellitus results in severe cardiovascular complications, and heart
      disease and failure remain the major causes of death in patients with diabetes.
      Given the increasing global tide of obesity and diabetes, the clinical burden of
      diabetes-induced cardiovascular disease is reaching epidemic proportions.
      Therefore urgent actions are needed to stem the tide of diabetes which entails
      new prevention and treatment tools. Clinical and pharmacological studies have
      demonstrated that AngII (angiotensin II), the major effector peptide of the RAS
      (renin-angiotensin system), is a critical promoter of insulin resistance and
      diabetes mellitus. The role of RAS and AngII has been implicated in the
      progression of diabetic cardiovascular complications and AT1R (AngII type 1
      receptor) blockers and ACE (angiotensin-converting enzyme) inhibitors have shown
      clinical benefits. ACE2, the recently discovered homologue of ACE, is a
      monocarboxypeptidase which converts AngII into Ang-(1-7) [angiotensin-(1-7)]
      which, by virtue of its actions on the MasR (Mas receptor), opposes the effects
      of AngII. In animal models of diabetes, an early increase in ACE2 expression and
      activity occurs, whereas ACE2 mRNA and protein levels have been found to decrease
      in older STZ (streptozotocin)-induced diabetic rats. Using the Akita mouse model
      of Type 1 diabetes, we have recently shown that loss of ACE2 disrupts the balance
      of the RAS in a diabetic state and leads to AngII/AT1R-dependent systolic
      dysfunction and impaired vascular function. In the present review, we will
      discuss the role of the RAS in the pathophysiology and treatment of diabetes and
      its complications with particular emphasis on potential benefits of the ACE2/Ang
      (1-7)/MasR axis activation. 

PMID- 24329565
TI  - High-resolution photoelectron spectroscopy of molecules.
AB  - Rotationally resolved photoelectron spectra can provide significant insight into
      the underlying dynamics of molecular photoionization. Here, we discuss and
      compare results of recent theoretical studies of rotationally resolved
      photoelectron spectra with measurements for molecules such as HBr, OH, NO, N2,
      CO, H20, H2CO, and CH3. These studies reveal the rich dynamics of quantum-state
      specific studies of molecular photoionization and provide a robust description of
      key spectral features resulting from Cooper minima, autoionization, alignment,
      partial-wave mixing, and interference in related experimental studies. 

PMID- 24329563
TI  - An evolving story of angiotensin-II-forming pathways in rodents and humans.
AB  - Lessons learned from the characterization of the biological roles of Ang-(1-7)
      [angiotensin-(1-7)] in opposing the vasoconstrictor, proliferative and
      prothrombotic actions of AngII (angiotensin II) created an underpinning for a
      more comprehensive exploration of the multiple pathways by which the RAS (renin
      angiotensin system) of blood and tissues regulates homoeostasis and its altered
      state in disease processes. The present review summarizes the progress that has
      been made in the novel exploration of intermediate shorter forms of
      angiotensinogen through the characterization of the expression and functions of
      the dodecapeptide Ang-(1-12) [angiotensin-(1-12)] in the cardiac production of
      AngII. The studies reveal significant differences in humans compared with rodents
      regarding the enzymatic pathway by which Ang-(1-12) undergoes metabolism.
      Highlights of the research include the demonstration of chymase-directed
      formation of AngII from Ang-(1-12) in human left atrial myocytes and left
      ventricular tissue, the presence of robust expression of Ang-(1-12) and chymase
      in the atrial appendage of subjects with resistant atrial fibrillation, and the
      preliminary observation of significantly higher Ang-(1-12) expression in human
      left atrial appendages. 

PMID- 24329567
TI  - Continuous renal replacement therapy reduces the systemic and pulmonary
      inflammation induced by venovenous extracorporeal membrane oxygenation in a
      porcine model.
AB  - Pulmonary changes in veno-venous extracorporeal membrane oxygenation (VV-ECMO)
      are rarely determined. We compared the contribution of VV-ECMO and cannulation
      based on the observation of pulmonary inflammatory reaction and parenchymal
      construction in a porcine model of low tidal volume (VT ) ventilation. We also
      evaluated the effect of adding continuous renal replacement therapy (CRRT) to the
      ECMO circuit, because CRRT is known to reduce systemic cytokine release induced
      by VV-ECMO. A total of 18 pigs undergoing low-VT ventilation were randomly
      divided into three groups (group 1, cannulation; group 2, VV-ECMO; group 3, VV
      ECMO + CRRT) and studied for 24 h. Hemodynamic and ventilation parameters were
      recorded. We assessed plasma and alveolar cytokines, expression of pulmonary
      inflammatory genes, histopathological grading, and ultrastructural changes of the
      lungs. During the process, inspiratory volume increased and PaO2 decreased in
      group 1. Systemic tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL
      6) levels increased at 2 h in group 2 and partly decreased in group 3. At 24 h,
      the levels of bronchoalveolar lavage fluid, TNF-alpha, and IL-6 in group 2 were
      remarkably higher than those in groups 1 and 3. Pulmonary mRNA expression of
      cytokines did not differ between the groups. We observed an increased score of
      pulmonary pathological findings in pro-inflammatory cell infiltration and
      interstitial thickening of the lungs in group 2. The epithelium of the blood-air
      barrier after VV-ECMO was swollen. In group 3, the pulmonary parenchyma and blood
      air barrier were well preserved. We concluded that in a porcine model of low-VT
      ventilation, both VV-ECMO and VV-ECMO in combination with CRRT provided adequate
      oxygenation and carbon dioxide removal. Compared with VV-ECMO alone, VV-ECMO in
      combination with CRRT better preserved the lung parenchyma by eliminating
      systemic cytokines.

PMID- 24329568
TI  - Purring in cats during auscultation: how common is it, and can we stop it?
AB  - OBJECTIVES: When cats purr during examination it is difficult to perform
      auscultation. The objective of this study was to determine the prevalence of
      purring in cats during examination, and identify interventions that could be used
      to stop purring. METHODS: Cats seen at a first opinion clinic were enrolled in
      the study and their purring status recorded. Thirty of the purring cats were
      exposed to up to three different interventions in an attempt to stop purring in a
      randomised controlled trial including blowing at the ear, use of an ethanol-based
      aerosol near the cat and proximity to a running tap. RESULTS: The 30 cats in the
      trial were subjected to a total of 54 attempts to stop purring, proximity to a
      running tap caused 17 of 21 (81%) cats to stop purring, blowing at the cat's ears
      worked in 2 of 15 (13%) cats, spraying an aerosol close to the cat was effective
      in 9 of 18 (50%) cases. In 2 cats (7%), none of the interventions interrupted
      purring. CLINICAL SIGNIFICANCE: This study provides evidence that placing a
      purring cat near a running tap and in proximity to the discharge of an ethanol
      based aerosol are effective measures to stop purring in order to allow
      auscultation.

PMID- 24329437
TI  - Search for top squarks in R-parity-violating supersymmetry using three or more
      leptons and b-tagged jets.
AB  - A search for anomalous production of events with three or more isolated leptons
      and bottom-quark jets produced in pp collisions at ?s=8 TeV is presented. The
      analysis is based on a data sample corresponding to an integrated luminosity of
      19.5 fb(-1) collected by the CMS experiment at the LHC in 2012. No excess above
      the standard model expectations is observed. The results are interpreted in the
      context of supersymmetric models with signatures that have low missing transverse
      energy arising from light top-squark pair production with R-parity-violating
      decays of the lightest supersymmetric particle. In two models with different R
      parity-violating couplings, top squarks are excluded below masses of 1020 GeV and
      820 GeV when the lightest supersymmetric particle has a mass of 200 GeV.

PMID- 24329569
TI  - Risk assessment and economic impact analysis of the implementation of new
      European legislation on radiopharmaceuticals in Italy: the case of the new
      monograph chapter Compounding of Radiopharmaceuticals (PHARMEUROPA, Vol. 23, No.
      4, October 2011).
AB  - An assessment of the new monograph chapter Compounding of Radiopharmaceuticals
      has been conducted on the basis of the first period of implementation of Italian
      legislation on Good Radiopharmaceuticals Practice (NBP) in the preparation of
      radiopharmaceuticals, in keeping with Decree by the Italian Ministry of Health
      dated March 30, 2005. This approach is well grounded in the several points of
      similarity between the two sets of regulations. The impact on patient risk, on
      staff risk, and on healthcare organization risk, has been assessed. At the same
      time, the actual costs of coming into compliance with regulations have been
      estimated. A change risk analysis has been performed through the identification
      of healthcare-associated risks, the analysis and measurement of the likelihood of
      occurrence and of the potential impact in terms of patient harm and staff harm,
      and the determination of the healthcare organization's controlling capability. In
      order to evaluate the economic impact, the expenses directly related to the
      implementation of the activities as per ministerial decree have been estimated
      after calculating the overall costs unrelated to NBP implementation. The
      resulting costs have then been averaged over the total number of patient services
      delivered. NBP implementation shows an extremely positive impact on risk
      management for both patients receiving Nuclear Medicine services and the
      healthcare organization. With regard to healthcare workers, instead, the
      implementation of these regulations has a negative effect on the risk for greater
      exposure and a positive effect on the defense against litigation. The economic
      impact analysis of NBP implementation shows a 34% increase in the costs for a
      single patient service. The implementation of the ministerial decree allows for
      greater detectability of and control over a number of critical elements, paving
      the way for risk management and minimization. We, therefore, believe that the
      proposed tool can provide basic criteria for analysis that could be used by other
      organizations setting about completing the same process. 

PMID- 24329566
TI  - Vascular targets for cannabinoids: animal and human studies.
AB  - Application of cannabinoids and endocannabinoids to perfused vascular beds or
      individual isolated arteries results in changes in vascular resistance. In most
      cases, the result is vasorelaxation, although vasoconstrictor responses are also
      observed. Cannabinoids also modulate the actions of vasoactive compounds
      including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane
      mimetic). Numerous mechanisms of action have been proposed including receptor
      activation, potassium channel activation, calcium channel inhibition and the
      production of vasoactive mediators such as calcitonin gene-related peptide,
      prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen
      peroxide. The purpose of this review is to examine the evidence for the range of
      receptors now known to be activated by cannabinoids. Direct activation by
      cannabinoids of CB1 , CBe , TRPV1 (and potentially other TRP channels) and PPARs
      in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1 A
      has also been identified in some studies. Indirectly, activation of prostanoid
      receptors (TP, IP, EP1 and EP4 ) and the CGRP receptor is involved in the
      vascular responses to cannabinoids. The majority of this evidence has been
      obtained through animal research, but recent work has confirmed some of these
      targets in human arteries. Vascular responses to cannabinoids are enhanced in
      hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to
      changes in the target sites of action. Much further work is required to establish
      the extent of vascular actions of cannabinoids and the application of this
      research in physiological and pathophysiological situations. LINKED ARTICLES:
      This article is part of a themed section on Cannabinoids 2013. To view the other
      articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6.

PMID- 24329570
TI  - Breaking barriers and building bridges: understanding the pervasive needs of
      older LGBT adults and the value of social work in health care.
AB  - Given the rise in the aging population and the increased use of health care
      services, there is a demand for awareness and training that targets underserved
      populations such as older lesbian, gay, bisexual, and transgender (LGBT) adults.
      Older LGBT adults are 5 times less likely to access health care and social
      services (King, 2009). Ethically responsible health service delivery is needed to
      capitalize on the strengths and capabilities of older LGBT adults and is vital
      for combating existing health disparities. Social workers aim to prevent ongoing
      gaps in care for older LGBT adults that can lead to negative individual and
      social consequences. 

PMID- 24329571
TI  - Relationship of semen hyperviscosity with IL-6, TNF-alpha, IL-10 and ROS
      production in seminal plasma of infertile patients with prostatitis and prostato
      vesiculitis.
AB  - Changes in levels of oxidative damage products in semen and their relationship to
      seminal fluid viscosity (SFV) have recently received increasing research
      interest. We analysed whether SFV was associated with ROS generation, levels of
      cytokines TNF-alpha (TNF-alpha), IL-6 and IL-10 and seminal leucocyte
      concentration, and whether ROS production was related to the extent of
      infections/inflammations at one (prostatitis) or two (prostato-vesiculitis) male
      accessory glands. We studied 169 infertile patients, with chronic bacterial
      prostatitis (PR, n = 74) and/or bilateral prostato-vesiculitis (PV, n = 95), as
      diagnosed by the ultrasound (US) criteria. Healthy fertile men (n = 42) served as
      controls. In the PV patient group, SFV, semen characteristics and ROS production
      had median values that were significantly higher than those found in PR patients
      and controls, although other sperm variables had values significantly lower than
      those found in PR patients or controls. In PV infertile patients, ROS generation
      and pro-inflammatory cytokines levels were higher than those found in PR
      infertile patients and controls, although seminal IL-10 levels in PV and PR
      patients were lower than those found in the controls. In PR patients, the levels
      of SFV were positively related to TNF-alpha (r = 0.67; P < 0.01), fMLP-stimulated
      ROS production in the 45% Percoll fraction (r = 0.687, P < 0.01) and the 90%
      Percoll fraction in basal condition (r = 0.695, P < 0.01), and after fMLP
      stimulation (r = 0.688, P < 0.01). Thus, our data indicated that seminal
      hyperviscosity is associated with increased oxidative stress in infertile men and
      increased pro-inflammatory interleukins in patients with male accessory gland
      infection, more when the infection was extended to the seminal vesicles. 

PMID- 24329575
TI  - Defining the rural HIV epidemic: correlations of 3 definitions--South Carolina,
      2005-2011.
AB  - PURPOSE: To gain a better understanding of the HIV epidemic in rural South
      Carolina (SC) by contrasting 3 definitions of rural and urban areas. METHODS: The
      sample included newly diagnosed HIV cases aged >=18 years in SC between January
      1, 2005, and December 31, 2011. Each individual was assigned a rural or urban
      status as defined by the Office of Management and Budget (OMB), Census Bureau
      (CB), and Rural Urban Commuting Area (RUCA) classifications. Descriptive
      statistics were conducted to compare sociodemographic characteristics, CD4
      counts, viral loads, and time to AIDS diagnosis between rural and urban
      populations. Kappa statistics measured the agreement between the 3 definitions of
      rurality. FINDINGS: Depending on the definition used, the proportion of newly
      diagnosed HIV cases in rural areas varied from 23.3% to 32.0%. Based on the OMB
      and RUCA definitions, rural residents with HIV were more likely to be older,
      women, black, and non-Hispanic, report heterosexual contact, and have an AIDS
      diagnosis within 1 year of their HIV diagnosis. The OMB and RUCA definitions had
      a nearly perfect agreement (kappa = 0.8614; 95% CI = 0.8457, 0.8772), while poor
      agreements were noted between the OMB and CB or the RUCA and CB definitions.
      CONCLUSION: When examining the rural HIV epidemic, how "rural" is defined
      matters. Using 3 definitions of rurality, statistically significant differences
      were found in demographic characteristics, timing of HIV diagnosis and the
      proportion of rural residents diagnosed with HIV in SC. The findings suggest
      possible misclassification biases that may adversely influence services and
      resource distribution.

PMID- 24329572
TI  - Comparative outcomes of everolimus, temsirolimus and sorafenib as second targeted
      therapies for metastatic renal cell carcinoma: a US medical record review.
AB  - OBJECTIVE: To compare outcomes of metastatic renal cell carcinoma (mRCC) patients
      treated with everolimus, temsirolimus, and sorafenib following initial treatment
      with a tyrosine kinase inhibitor (TKI) in community and academic practices
      throughout the US. RESEARCH DESIGN AND METHODS: Medical records of mRCC patients
      who received everolimus, temsirolimus or sorafenib as their second therapy
      following a TKI were retrospectively reviewed from a nationally representative
      panel of oncologists. Overall survival (OS) and progression-free survival (PFS)
      of second targeted therapies were compared using multivariable Cox proportional
      hazard models, with adjustment for demographics, disease severity and prior
      treatments. RESULTS: A total of 233, 178, and 123 mRCC patients receiving
      everolimus, temsirolimus, and sorafenib, respectively, as second targeted
      therapies were included. Eighty-six percent used sunitinib and the remainder used
      sorafenib or pazopanib as their initial TKI. After adjusting for baseline
      characteristics, everolimus was associated with significantly prolonged OS
      (hazard ratio [HR] 0.60; CI 0.42-0.85; p = 0.004) and PFS (HR 0.73; CI 0.54-0.97;
      p = 0.032) compared to temsirolimus. Everolimus was associated with significantly
      longer OS (HR 0.66; CI 0.44-0.99; p = 0.045) and numerically longer PFS compared
      to sorafenib. No significant differences were observed between temsirolimus and
      sorafenib. LIMITATIONS: Despite adjustment for multiple patient characteristics,
      comparisons between treatment groups may be confounded by unobserved factors in
      this retrospective observational study. Tolerability outcomes were not collected.
      CONCLUSIONS: In this retrospective, non-randomized study of mRCC patients with
      prior TKI treatment, everolimus was associated with significantly prolonged OS
      and PFS compared to temsirolimus and significantly prolonged OS compared to
      sorafenib.

PMID- 24329573
TI  - One program, multiple training sites: does site of family medicine training
      influence professional practice location?
AB  - INTRODUCTION: Numerous strategies have been suggested to increase recruitment of
      family physicians to rural communities and smaller regional centers. One approach
      has been to implement distributed postgraduate education programs where trainees
      spend substantial time in such communities. The purpose of the current study was
      to compare the eventual practice location of family physicians who undertook
      their postgraduate training through a single university but who were based in
      either metropolitan or distributed, non-metropolitan communities. METHODS: Since
      1998, the Department of Family Practice at the University of British Columbia in
      Canada has conducted an annual survey of its residents at 2, 5, and 10 years
      after completion of training. The authors received Ethics Board approval to use
      this anonymized data to identify personal and educational factors that predict
      future practice location. RESULTS: The overall response rate was 45%. At 2 years
      (N=222), residents trained in distributed sites were 15 times more likely to
      enter practice in rural communities, small towns and regional centers than those
      who trained in metropolitan teaching centers. This was even more predictive for
      retention in non-urban practice sites. Among the subgroup of physicians who
      remained in a single practice location for more than a year preceding the survey,
      those who trained in smaller sites were 36 times more likely to choose a rural or
      regional practice setting. While the vast majority of those trained in
      metropolitan sites chose an urban practice location, a subgroup of those with
      some rural upbringing were more likely to practice in rural or regional settings.
      Trainees from distributed sites considered themselves more prepared for practice
      regardless of ultimate practice location. CONCLUSIONS: Participation in a
      distributed postgraduate family medicine training site is an important predictor
      of a non-urban practice location. This effect persists for 10 years after
      completion of training and is independent of other predictors of non-urban
      practice including gender, rural upbringing, and rural undergraduate training. It
      is hypothesized that this is due not only to a curriculum that supports
      preparedness for this type of practice but also to opportunities to develop
      personal and professional roots in these communities.

PMID- 24329576
TI  - Processing maize flour and corn meal food products.
AB  - Corn is the cereal with the highest production worldwide and is used for human
      consumption, livestock feed, and fuel. Various food technologies are currently
      used for processing industrially produced maize flours and corn meals in
      different parts of the world to obtain precooked refined maize flour, dehydrated
      nixtamalized flour, fermented maize flours, and other maize products. These
      products have different intrinsic vitamin and mineral contents, and their
      processing follows different pathways from raw grain to the consumer final
      product, which entail changes in nutrient composition. Dry maize mechanical
      processing creates whole or fractionated products, separated by anatomical
      features such as bran, germ, and endosperm. Wet maize processing separates by
      chemical compound classification such as starch and protein. Various industrial
      processes, including whole grain, dry milling fractionation, and nixtamalization,
      are described. Vitamin and mineral losses during processing are identified and
      the nutritional impacts outlined. Also discussed are the vitamin and mineral
      contents of corn. 

PMID- 24329574
TI  - Biochemical and physiological mechanisms underlying effects of Cucumber mosaic
      virus on host-plant traits that mediate transmission by aphid vectors.
AB  - The transmission of insect-vectored diseases entails complex interactions among
      pathogens, hosts and vectors. Chemistry plays a key role in these interactions;
      yet, little work has addressed the chemical ecology of insect-vectored diseases,
      especially in plant pathosystems. Recently, we documented effects of Cucumber
      mosaic virus (CMV) on the phenotype of its host (Cucurbita pepo) that influence
      plant-aphid interactions and appear conducive to the non-persistent transmission
      of this virus. CMV reduces host-plant quality for aphids, causing rapid vector
      dispersal. Nevertheless, aphids are attracted to the elevated volatile emissions
      of CMV-infected plants. Here, we show that CMV infection (1) disrupts levels of
      carbohydrates and amino acids in leaf tissue (where aphids initially probe plants
      and acquire virions) and in the phloem (where long-term feeding occurs) in ways
      that reduce plant quality for aphids; (2) causes constitutive up-regulation of
      salicylic acid; (3) alters herbivore-induced jasmonic acid biosynthesis as well
      as the sensitivity of downstream defences to jasmonic acid; and (4) elevates
      ethylene emissions and free fatty acid precursors of volatiles. These findings
      are consistent with previously documented patterns of aphid performance and
      behaviour and provide a foundation for further exploration of the genetic
      mechanisms responsible for these effects and the evolutionary processes that
      shape them. 

PMID- 24329578
TI  - Does cyclophosphamide still have a role in the treatment of severe inflammatory
      eye disease?
AB  - Cyclophosphamide is a highly effective immunosuppressive drug that has proven
      efficacy in the treatment of patients with severe inflammatory eye disease. It
      has the advantage of being able to be used either orally or intravenously, has a
      potent steroid-sparing effect, and is effective in inducing disease remission.
      The major limitations to the use of this alkylating agent are its frequent side
      effects. With the increasing availability of alternate forms of therapy it is
      time to review the therapeutic regimen for cyclophosphamide use in patients with
      inflammatory eye disease.

PMID- 24329579
TI  - Topical skin targeting effect of penetration modifiers on hairless mouse skin,
      pig abdominal skin and pig ear skin.
AB  - OBJECTIVE: This study was to investigate the topical skin targeting effects and
      mechanism of combination penetration modifiers of 1,2-hexanediol (or 1,2
      heptanediol) and 1,4-cyclohexanediol on transdermal absorption of metronidazole
      (MTZ) in different skin models. METHODS: Six formulations were applied to pig
      abdominal skin and pig ear skin models, respectively, and the results were
      compared with the previous data on hairless mouse skin worked out by our
      laboratory. Four parameters (flux, Tlag, Q24 and targeting ratio) were used to
      evaluate permeability and targeting effect in skin. RESULTS: The combined
      penetration modifiers played a general role on decreasing permeability without
      reducing skin retention. The most significant skin permeability decrement to MTZ
      was pig abdominal skin (permeability decrement was ~20% for hairless mouse skin,
      60% for pig abdominal skin and 40% for pig ear skin, respectively) while the
      strongest skin targeting effect appeared in hairless mouse skin (targeting ratios
      were 1.79 for hairless mouse skin, 1.24 for pig abdominal skin and 1.05 for pig
      ear skin, respectively) under the role of penetration modifiers. CONCLUSIONS:
      Thickness of stratum corneum (SC) was the major factor impact on skin targeting
      effect. Selection criteria of skin models also have been discussed in this study.

PMID- 24329577
TI  - Chemosensitization of cancer cells via gold nanoparticle-induced cell cycle
      regulation.
AB  - We have previously shown that plasmonic nanoparticles conjugated with nuclear
      targeting and cytoplasm-targeting peptides (NLS and RGD, respectively) are
      capable of altering the cell cycle of human oral squamous carcinoma cells (HSC
      3). In the present work, we show that this regulation of the cell cycle can be
      exploited to enhance the efficacy of a common chemotherapeutic agent, 5
      Fluorouracil, by pretreating cells with gold nanoparticles. Utilizing flow
      cytometry cell cycle analysis, we were able to quantify the 5-Fluorouracil
      efficacy as an accumulation of cells in the S phase with a depletion of cells in
      the G2/M phase. Two gold nanoparticle sizes were tested in this work; 30 nm with
      a surface plasmon resonance at 530 nm and 15 nm with a surface plasmon resonance
      at 520 nm. The 30 nm nuclear-targeted gold nanoparticles (NLS-AuNPs) showed the
      greatest 5-Fluorouracil efficacy enhancement when 5-Fluorouracil treatment (500
      MUm, 48 h) is preceded by a 24-h treatment with nanoparticles. In conclusion, we
      show that nuclear-targeted 30 nm gold nanoparticles enhance 5-Fluorouracil drug
      efficacy in HSC-3 cells via regulation of the cell cycle, a chemosensitization
      technique that could potentially be expanded to different cell lines and
      different chemotherapies.

PMID- 24329580
TI  - Equine Veterinary Journal: Recent and future directions.

PMID- 24329581
TI  - Advances in the understanding of tendinopathies: a report on the Second Havemeyer
      Workshop on equine tendon disease.

PMID- 24329582
TI  - The future of helminth control in horses.

PMID- 24329583
TI  - Heritability and the equine clinician.

PMID- 24329584
TI  - The dilemmas of medicine selection for equine veterinarians.

PMID- 24329585
TI  - EVE and EVJ online collection of equine endocrinology: recent and future
      directions; a great start, but still a long way to go.

PMID- 24329586
TI  - Current status and future directions: equine pituitary pars intermedia
      dysfunction and equine metabolic syndrome.

PMID- 24329588
TI  - Prostate cancer incidence in orchidectomised male-to-female transsexual persons
      treated with oestrogens.
AB  - Male-to-female transsexual persons (MtoF) undergo treatment with antiandrogens
      and oestrogens followed by bilateral orchiectomy. The aim of this study was to
      investigate the incidence of prostate cancer (PCa) in a cohort of MtoF
      individuals. Medical records 2306 MtoF treated between 1975 and 2006 of the
      Amsterdam Gender Clinic were reviewed. Mean age at initiation of treatment was
      29.3 +/- 12.7 years (range 16-83). Mean follow-up was 21.4 years, resulting in a
      combined total of 51 173 person-years of exposure and follow-up. Follow-up more
      than 20 years was available for 303 individuals, including follow-up of more than
      30 years in 151 individuals. A single case of PCa was identified in this group.
      The overall incidence of PCa in this population was 0.04% and 0.13% for
      individuals who had initiated hormonal treatment after at 40 years or later. PCa
      in this large MtoF population was rare. However, underdiagnosis is likely due to
      lack of close prostate monitoring and suppression of PSA due to androgen
      deprivation. In addition, only a limited number of MtoF individuals have yet
      reached old age when PCa becomes more common. When diagnosed in this population,
      there appears to be a tendency for PCa to behave aggressively. Prostate
      monitoring should be considered in these individuals beginning at age 50 years. 

PMID- 24329589
TI  - Management of erythropoiesis: cross-sectional study of the relationships between
      erythropoiesis and nutrition, physical features, and adiponectin in 3519 Japanese
      people.
AB  - Although erythroid abnormalities (anemia and polycythemia) are commonly observed
      pathological conditions, not much information about borderline abnormalities is
      available. In this study, a cross-sectional study to analyze the relationships
      between erythropoiesis and nutrition, physical features, and laboratory test
      findings was conducted in middle-aged and older men and women. The study included
      3519 Japanese people (1579 men and 1940 women), age 40 years and over. Analysis
      of variance showed that the group with a tendency to anemia was older, had a
      lower body mass index and diastolic blood pressure, and had higher serum
      adiponectin and creatinine. Multiple regression analysis showed that adiponectin,
      triglycerides, and total protein were common factors that affected erythropoiesis
      in both men and women. Hepatic, renal, and cardiac functions were also factors
      involved in erythropoiesis in men and in postmenopausal women. In addition,
      nutrient factors such as alcohol, vitamins, and carbohydrates were also
      significantly involved in erythropoiesis in men, but there were no significant
      nutrient factors involved in erythropoiesis in either premenopausal or
      postmenopausal women. This study showed that factors that influence
      erythropoiesis differ between men, premenopausal women, and postmenopausal women,
      and it suggested that appropriately modifying erythropoiesis management for each
      group of people is essential. 

PMID- 24329590
TI  - A study to demonstrate the use of FNA cytology rather than biopsy in the
      diagnosis of neonatal biliary atresia.
AB  - OBJECTIVE: To study the use of fine needle aspiration (FNA) cytology in neonatal
      biliary atresia (BA). METHODS: Twelve female and nine male patients (age range, 3
      7 months; mean age, 4.5 months) with a pre-operative diagnosis of BA, who were
      scheduled for Kasia portoenterostomy and selected for intraoperative FNA, were
      studied. RESULTS: Cholestasis, bile deposits, bile infarcts, hepatitic rosettes
      enclosing bile plugs, feathery degeneration of hepatocytes and inflammatory cells
      were seen in the cytological slides. Bile infarcts, rosette formation and
      inflammatory cells were mainly noticed in type 3 BA. Bile infarcts and hepatitic
      rosettes are surrogate findings for the diagnosis of the obstructive type of
      cholestasis. CONCLUSION: With the help of imaging studies, FNA in a
      multidisciplinary setting can be diagnostic of neonatal BA when cytological
      features suggest the obstructive nature of cholestasis, but this procedure cannot
      replace completely liver biopsy for this diagnosis.

PMID- 24329591
TI  - The zebrafish infraorbital bones: a descriptive study.
AB  - The infraorbital (IO) bone series, a component of the circumorbital series, makes
      up five of the eight dermal bones found in the orbital region of the zebrafish
      skull. Ossifying in a set sequence, the IOs are closely associated with the
      cranial lateral line system as they house neuromast sensory receptors in bony
      canals. We conducted a detailed analysis of the condensation to mineralization
      phases of development of these bones. Our analyses involved both bone and
      osteoblast staining of zebrafish at 20 different time points. IO bone
      condensations are shaped as templates for the final bone shape, and they
      mineralize at one or more centers of ossification. Initially, mineralization is
      closely associated with the lateral line canals and/or foramen, and the onset of
      mineralization is temporally variable. Canal wall mineralization is a process
      that continues into adulthood and completely mineralized canal roofs were not
      found. Our comprehensive growth series detailing the ossification of each IO bone
      provides important insight into the growth and development of this series of
      neural crest-derived flat bones in the zebrafish craniofacial skeleton.

PMID- 24329592
TI  - Effect of different selenium sources on production performance and biochemical
      parameters of broilers.
AB  - Selenium (Se) is an essential trace element for animal and human. Supplementation
      of Se usually in livestock diet has been proved as effective element. This study
      was conducted to investigate the effect of different sources of selenium on
      growth performance, slaughter performance, immune trait, oxidation resistance,
      meat quality and selenium content in tissue of broilers to comprehensively
      evaluate the effect of selenium. A total of 324 1-day-old AA broilers were
      selected and randomly allocated to three treatments of six replicates with 18
      broilers each. The trial period was 42 days and was divided into two periods. Our
      results showed that effect of different sources of selenium on growth
      performance, slaughter performance, the immune status, drip loss and flesh had
      not significant difference (p > 0.05); while the activities of serum glutathione
      peroxidase (GSH-Px), total superoxide dismutase (T-SOD), the abilities to inhibit
      hydroxyl radical (OH) and total antioxidant capacity (T-AOC) were significantly
      higher in selenium yeast than sodium selenite groups, and the contents of MDA of
      selenium yeast groups were significantly lower than that of sodium selenite. This
      study demonstrated that the different sources of selenium had no obvious effect
      on production performance of broilers, but significantly influenced the broiler
      oxidation resistance. 

PMID- 24329593
TI  - Statewide implementation of "reducing disability in Alzheimer's disease": impact
      on family caregiver outcomes.
AB  - There have been few replications of efficacious evidence-based programs for
      dementia caregivers offered in community settings. This study highlights the
      replication of the evidence-based Reducing Disability in Alzheimer's Disease
      program and explores the changes in outcomes for participating caregivers and
      whether those changes are related to level of program utilization. With data from
      219 caregivers, regression results indicate that more exercise sessions are
      associated with a decrease in caregiver strain and more behavior management
      sessions are associated with a decrease in unmet needs after 3 months. Findings
      demonstrate how a multicomponent program can have positive benefits for family
      caregivers. 

PMID- 24329594
TI  - A study of the attitude of Latin-American residents in Spain toward organ
      xenotransplantation.
AB  - BACKGROUND: It is important to find out what would be the level of acceptance of
      xenotransplantation in society, especially in populations where there are
      preclinical trials. The Latin-American population is growing in Spain, given the
      cultural, religious, and language similarities. OBJECTIVES: (i) to analyze
      attitude toward xenotransplantation in the population born in Latin America and
      now residing in Spain; and (ii) to establish the variables that affect this
      attitude. METHOD: A sample of Latin-American residents in Spain was obtained
      randomly in 2010 and stratified by the respondent's nationality (n = 1.314).
      Attitude was evaluated using a validated questionnaire (PCID-XenoTx Rios), which
      was completed anonymously and self-administered. STATISTICAL ANALYSIS: Student's
      t-test, the Chi-squared test, Fisher's exact test, and logistic regression
      analysis. RESULTS: The questionnaire completion rate was 89% (n = 1.165). If it
      was assumed that xenotransplanted organs functioned as well as human ones, 40%
      were in favor, 19% against, and 41% undecided. This attitude is related to: age
      (P = 0.003); sex (P = 0.002); level of education (P < 0.001); descendents (P =
      0.003); country of origin (P < 0.001); participation in voluntary prosocial
      activities (P = 0.006); having spoken about donation and transplantation within
      the family (P < 0.001); a partner's favorable attitude toward transplantation (P
      < 0.001); previous experience of donation and/or transplantation (P < 0.001); a
      belief that one might need a transplant in the future (P < 0.001); and a
      favorable attitude toward human donation, both deceased as well as living (P <
      0.001). In the multivariate analysis, the following variables continue to feature
      as independent variables: age (older: Odds Ratio = 1.041); sex (male: OR =
      1.579); level of education (university: OR = 2.770); descendents (none: OR =
      2.386); a partner's attitude toward transplantation (favorable: OR = 2.262);
      attitude toward deceased organ donation (favorable: OR = 1.587); previous
      experience of donation and/or transplantation (OR = 1.519); a belief that one
      might need a transplant in the future (OR = 1.675); and attitude toward related
      living donation (in favor: OR = 4.405). CONCLUSIONS: Latin Americans who usually
      reside in Spain have a more negative attitude toward xenotransplantation than the
      native Spanish population, and their attitude is affected by many psychosocial
      factors, mainly related to previous attitude toward the different types of human
      organ donation.

PMID- 24329595
TI  - Expected and experienced pain during epidural catheter insertion.
AB  - BACKGROUND: Insertion of an epidural catheter for pain relief is frequently used
      in anaesthetic practice. Little is known regarding patients' expected vs.
      experienced pain and discomfort due to the epidural block procedure. The purpose
      of this study was to investigate the expected and experienced pain, respectively,
      associated with the epidural procedure in patients undergoing major abdominal
      surgery. METHODS: Thirty adult, unselected patients scheduled for elective major
      abdominal surgery were included in this study, which was approved by the ethics
      committee. Pre-operative insertion of an epidural catheter had to be a part of
      the anaesthetic routine procedure. Immediately before the epidural procedure, the
      patients were asked to grade the pain they expected from the procedure on an 11
      point numeric rating system scale, ranging from 0 to 10, where '0' is no pain and
      '10' is worst imaginable pain. When the procedure had been carried out, the
      patients were once again asked to grade how much pain they had experienced.
      RESULTS: The median expected pain as a result of the epidural procedure was 5.0.
      Median experienced pain was 2.0. The median difference between the expected and
      experienced pain was -3.0 (P < 0.0001). The only patient who expected less pain
      than she subsequently experienced had a paraesthetic sensation. Gender, age, or
      previous experience from central neuraxial block did not significantly affect
      neither expected nor experienced pain. CONCLUSIONS: Patients expect significantly
      more pain than they experience from receiving an epidural block.

PMID- 24329596
TI  - Quantile regression in the study of developmental sciences.
AB  - Linear regression analysis is one of the most common techniques applied in
      developmental research, but only allows for an estimate of the average relations
      between the predictor(s) and the outcome. This study describes quantile
      regression, which provides estimates of the relations between the predictor(s)
      and outcome, but across multiple points of the outcome's distribution. Using data
      from the High School and Beyond and U.S. Sustained Effects Study databases,
      quantile regression is demonstrated and contrasted with linear regression when
      considering models with: (a) one continuous predictor, (b) one dichotomous
      predictor, (c) a continuous and a dichotomous predictor, and (d) a longitudinal
      application. Results from each example exhibited the differential inferences
      which may be drawn using linear or quantile regression. 

PMID- 24329597
TI  - Description of healthcare needs at an episodic clinic in rural southwest
      Virginia.
AB  - INTRODUCTION: The objective of this study was to describe the population served
      at an episodic clinic in Southwest Virginia to better understand patient needs at
      a yearly episodic Remote Area Medical (RAM) clinic that provides free healthcare
      services. METHODS: The dataset was compiled retrospectively from 2834 medical
      records from RAM patients between 1 July 2006 and 31 July 2008. Information was
      de-identified and manually recorded from paper records. The data were analyzed
      using descriptive statistics and compared to pre-existing estimates from the
      region. FINDINGS: The number and type of services rendered at the RAM clinic each
      year varied greatly, and was dependent on the availability of staff and supplies.
      Diabetes, hypertension, and other prevalent diseases were reported, and an
      overwhelming majority (74%) of patients were overweight or obese. In 2008, 62% of
      patients were uninsured, 44% had no primary care physician, and a majority of
      patients were diagnosed with hypertension or poorly managed diabetes.
      CONCLUSIONS: Chronic diseases including obesity, hypertension, diabetes, and
      arthritis plague the Appalachian region. However, better knowledge of the
      medically underserved in this region can help address the patient's needs through
      RAM clinics and other accessible health clinics by increasing patient and
      physician awareness of available services, decreasing patient waiting time, and
      improving medical recordkeeping.

PMID- 24329598
TI  - Phosphatidylcholine biosynthesis in Xanthomonas campestris via a yeast-like
      acylation pathway.
AB  - Two principal phosphatidylcholine (PC) biosynthesis pathways are known in
      bacteria. S-adenosylmethionine (SAM)-dependent phospholipid N-methyltransferases
      (Pmt) catalyse the threefold N-methylation of phosphatidylethanolamine (PE) to
      PC. In an alternative pathway, the PC synthase (Pcs) condenses CDP-diacylglycerol
      and choline to produce PC. In this study, we investigated phospholipid
      biosynthesis in the plant pathogen Xanthomonas campestris that was found to
      contain significant amounts of monomethylated PE (MMPE) and small amounts of PC.
      We identified a Pmt enzyme that produces MMPE without methylating it further to
      PC. Surprisingly, PC production was independent of [(14) C]-SAM and [(14) C]
      choline excluding canonical Pmt or Pcs pathways. Feeding experiments with various
      choline derivatives revealed a novel, yeast-like PC synthesis route in
      Xanthomonas, in which two acyl side-chains are added to a glycerophosphocholine
      (GPC) backbone. Two out of 12 tested acyltransferases from Xanthomonas were able
      to catalyse the second acylation step from lyso-PC to PC. This first description
      of GPC-dependent PC production in bacteria illustrates an unexpected diversity of
      PC biosynthesis pathways. 

PMID- 24329599
TI  - Cytological and histological correlation in diagnosing feline and canine
      mediastinal masses.
AB  - OBJECTIVES: The aim of this study was to evaluate the agreement between
      cytological and histological diagnosis of canine and feline mediastinal masses to
      assess the utility of cytological examination in accurately diagnosing and
      classifying mediastinal lesions. METHODS: A retrospective review of 58 cases of
      mediastinal masses from 21 dogs and 37 cats were performed. Histopathology was
      used as the diagnostic reference standard. The agreement between cytological and
      histological diagnosis was calculated. RESULTS: The complete agreement between
      cytological and histological classification ranged from substantial (k = 0 . 72,
      CI: 0 . 64 to 0 . 80) to almost perfect (k = 0 . 89, CI: 0 . 82 to 0 . 96)
      depending on how the cytological diagnoses classified as suspicious were used for
      statistical calculations. CLINICAL SIGNIFICANCE: Cytological examination of
      canine and feline mediastinal masses is a relatively easy, low-cost procedure,
      with good agreement with final histological diagnoses.

PMID- 24329600
TI  - Attenuation of steatohepatitis, fibrosis, and carcinogenesis in mice fed a
      methionine-choline deficient diet by CCAAT/enhancer-binding protein homologous
      protein deficiency.
AB  - BACKGROUND AND AIMS: Hepatic steatosis is a metabolic liver disease with the
      potential to progress to steatohepatitis, cirrhosis, and hepatocellular carcinoma
      (HCC). The aim of this study was to investigate the impact of CCAAT/enhancer
      binding protein homologous protein (CHOP) deficiency in the development of
      steatosis-associated progression of HCC. METHODS: Eight-week-old wild-type (WT)
      and CHOP knockout (CHOP-/-) mice were fed a normal or methionine-choline
      deficient (MCD) diet. Mice were sacrificed after 3 weeks, and steatosis,
      inflammation, apoptosis, and liver damage were assessed. We also evaluated
      fibrosis after 8 weeks of nutrition intervention. To explore the role of CHOP in
      liver carcinogenesis, 25 mg/kg of diethylnitrosamine (DEN) was injected
      intraperitoneally into 2-week-old mice, which were then fed the aforementioned
      diets from 8 to 24 weeks of age. CHOP expression in HCC patient livers was also
      evaluated. RESULTS: CHOP deficiency did not affect steatosis but significantly
      reduced apoptotic cells, inflammation scores, and serum liver enzymes. It also
      significantly suppressed total serum bilirubin levels, fibrotic area size, and
      messenger RNA expression of profibrotic cytokines. DEN-initiated carcinogenesis
      was promoted by the MCD diet, while CHOP deficiency significantly attenuated the
      total number and maximum diameter of tumors and the Ki-67 labeling index. In
      human livers, CHOP expression was enhanced in parallel with non-alcoholic
      steatohepatitis-to-HCC progression. CONCLUSIONS: CHOP deficiency attenuated
      apoptosis, inflammation, fibrosis, and tumorigenesis under fat-loading
      conditions, indicating that a therapeutic strategy targeting CHOP might be
      effective for fat-induced liver injury and protecting against promotion of
      carcinogenesis in patients with liver steatosis.

PMID- 24329601
TI  - Lack of nitrogen as a causing agent of Cylindrospermopsis raciborskii
      intermittent blooms in a small tropical reservoir.
AB  - Cylindrospermopsis raciborskii is the focus of many studies due to its toxicity
      and increasing blooms frequency. The comprehension of the factors that might
      trigger these blooms is fundamental for the maintenance of good freshwater
      quality. To better understand the autoecology of C. raciborskii and to identify
      the factors controlling its dominance, general limnological features were
      evaluated in Pedalinhos reservoir, Brazil. Samplings were performed monthly
      between 2011 and 2013. Although C. raciborskii is considered a relatively
      perennial species in the tropics, it presented an interesting nonunimodal
      variation, with biovolume varying from 0 to c. 30 mm3 L-1 in short time intervals
      (< 30 days). These temporal trends allowed the evaluation of the isolated effects
      of nonclimatic variables. Cylindrospermopsis raciborskii was connected with
      several variables, but nitrogen was the major determinant of its dynamics. Blooms
      were observed when dissolved inorganic nitrogen (DIN) was scarce (< 50 MUg L-1),
      mainly in relation to the availability of phosphorus and total-N (DIN : total-P <
      3 and DIN : total-N < 0.04). This paper contributes to establish strategies to
      avoid C. raciborskii blooms, suggesting that a management in P levels would be
      not sufficient. It is necessary to consider N availability to avoid its dominance
      in the reservoir.

PMID- 24329602
TI  - External infrared reflection absorption spectrometry of monolayer films at the
      air-water interface.
AB  - The theory and practice of external infrared reflection absorption spectrometry
      (IRRAS) as applied to monomolecular films at the air-water interface are
      reviewed. The observed IR frequencies for films of amphiphilic species provide
      information about the conformational states of the hydrocarbon chains and the
      hydrogen bonding and ionization states of the polar head groups, under conditions
      of controlled surface pressure. Determination of molecular orientation is also
      feasible and requires detailed consideration of the reflection-absorption
      properties of the three- phase (air-monolayer-water) system. Current theoretical
      approaches are described. Applications of IRRAS to the study of single- and
      double-chain amphiphiles and proteins are reviewed, and initial excursions into
      biochemistry (interfacial enzyme catalysis) and physiology (pulmonary surfactant
      function) are reported. 

PMID- 24329603
TI  - Symptoms, clusters and quality of life prior to surgery for breast cancer.
AB  - AIMS AND OBJECTIVES: To examine the pretreatment symptoms and symptom clusters
      that women awaiting breast cancer surgery are experiencing and the impact of
      these symptoms on their quality of life. BACKGROUND: Most women diagnosed with
      breast cancer will have surgery as a first-line treatment. The presence of
      presurgery symptoms may be significant in contributing to distress and impaired
      quality of life. While it seems that women with breast cancer may experience the
      symptoms of fatigue, pain, depression and sleep disturbance as a cluster, this
      has not yet been confirmed by empirical research in the presurgery time period.
      DESIGN: A multiple-point prospective longitudinal cohort panel design is used.
      METHODS: Presurgery symptoms and quality of life were assessed using the Hospital
      Anxiety and Depression Scale, Insomnia Severity Index, Functional Assessment of
      Cancer Therapy-Fatigue, Brief Pain Inventory and the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire Core 30(3).
      RESULTS: Participants (n = 94, age range 30-92) experienced symptoms prior to
      surgery, with pain being a more prevalent symptom (35%) than fatigue (32%), sleep
      disturbances (25.5%) or depression (11%). global quality of life was
      significantly impacted on by fatigue and showed a moderate correlation with
      emotional functioning and a weak correlation with physical and social
      functioning. Hierarchical cluster analysis identified the presence of five
      clusters with symptoms present in differing intensities in each cluster.
      CONCLUSION: In this cohort of women, healthy other than having a diagnosis of
      breast cancer, symptoms were impacting on quality of life. It is evident that
      clusters of symptoms are present presurgery that must be assessed and managed.
      RELEVANCE TO PRACTICE: Healthcare delivery systems must ensure that early
      symptoms are addressed effectively in the presurgery period to improve quality of
      life and reduce adverse outcomes postsurgery.

PMID- 24329604
TI  - Targeting CD28 to prevent transplant rejection.
AB  - INTRODUCTION: The pivotal role of costimulatory pathways in regulating T-cell
      activation versus tolerance has stimulated tremendous interest in their
      manipulation for therapeutic purposes. Of these, the CD28-B7 pathway is arguably
      the most important and best studied. Therapeutic targets of CD28 are currently
      used in the treatment of melanoma, autoimmune diseases and in transplantation.
      AREAS COVERED: In this review, we summarize our current knowledge of CD28 and
      cytotoxic T-lymphocyte antigen-4 (CTLA-4) signaling, and review the current state
      and challenges of harnessing them to promote transplant tolerance. EXPERT
      OPINION: Despite the success of belatacept, a first-in-class CTLA-4 fusion
      protein now clinically used in transplantation, it is apparent that we have only
      scratched the surface in understanding the complexities of how costimulatory
      pathways modulate the immune system. Our initial assumption that positive
      costimulators activate effector T cells and prevent tolerance, while negative
      costimulators inhibit effector T cells and promote tolerance, is clearly an
      oversimplified view. Indeed, belatacept is not only capable of blocking
      deleterious CD28-B7 interactions that promote effector T-cell responses but can
      also have undesired effects on tolerogenic regulatory T-cell populations.

PMID- 24329605
TI  - Proton pump inhibitor-induced clear cell change.

PMID- 24329606
TI  - Metabolic analysis of the increased adventitious rooting mutant of Artemisia
      annua reveals a role for the plant monoterpene borneol in adventitious root
      formation.
AB  - Adventitious root (AR) formation is a critical process for plant clonal
      propagation. The role of plant secondary metabolites in AR formation is still
      poorly understood. Chemical and physical mutagenesis in combination with somatic
      variation were performed on Artemisia annua in order to obtain a mutant with
      changes in adventitious rooting and composition of plant secondary metabolites.
      Metabolic and morphological analyses of the iar (increased adventitious rooting)
      mutant coupled with in vitro assays were used to elucidate the relationship
      between plant secondary metabolites and AR formation. The only detected
      differences between the iar mutant and wild-type were rooting capacity and
      borneol/camphor content. Consistent with this, treatment with borneol in vitro
      promoted adventitious rooting in wild-type. The enhanced rooting did not continue
      upon removal of borneol. The iar mutant displayed no significant differences in
      AR formation upon treatment with camphor. Together, our results suggest that
      borneol promotes adventitious rooting whereas camphor has no effect on AR
      formation. 

PMID- 24329607
TI  - The role of illness beliefs and coping in the adjustment to dentine
      hypersensitivity.
AB  - AIM: Dentine hypersensitivity is a common oral health problem, however, there has
      been little research on how people cope with this condition. This study aimed to
      quantify the effects of illness beliefs and coping strategies on the health
      outcomes of individuals with dentine hypersensitivity. MATERIALS AND METHODS:
      Participants were purposively sampled from students and staff in one large UK
      University and 101 self-diagnosed dentine hypersensitivity sufferers participated
      in the longitudinal study. Participants were required to complete questionnaires
      which assessed health anxiety, specific illness beliefs (control, consequences,
      illness coherence, timeline perspectives and emotional representations), coping
      strategies (passive and active coping) and oral health-related and health-related
      quality of life (OHRQoL and HRQoL) at baseline and 1 month follow-up. RESULTS:
      Over half of the participants (N = 56) experienced sensations in their teeth on a
      daily basis and the majority had experienced dentine hypersensitivity for at
      least 1 year (N = 87). Structural equation modelling indicated that predictors of
      OHRQoL and HRQoL impacts at follow-up were frequency of sensations, low levels of
      illness coherence, negative emotional representations, greater health anxiety and
      use of passive coping strategies at baseline. CONCLUSIONS: Illness beliefs and
      coping strategies predict oral and health-related quality of life outcomes in
      people with dentine hypersensitivity.

PMID- 24329609
TI  - Equity in access to fortified maize flour and corn meal.
AB  - Mass fortification of maize flour and corn meal with a single or multiple
      micronutrients is a public health intervention that aims to improve vitamin and
      mineral intake, micronutrient nutritional status, health, and development of the
      general population. Micronutrient malnutrition is unevenly distributed among
      population groups and is importantly determined by social factors, such as living
      conditions, socioeconomic position, gender, cultural norms, health systems, and
      the socioeconomic and political context in which people access food. Efforts
      trying to make fortified foods accessible to the population groups that most need
      them require acknowledgment of the role of these determinants. Using a
      perspective of social determinants of health, this article presents a conceptual
      framework to approach equity in access to fortified maize flour and corn meal,
      and provides nonexhaustive examples that illustrate the different levels included
      in the framework. Key monitoring areas and issues to consider in order to expand
      and guarantee a more equitable access to maize flour and corn meal are described.

PMID- 24329611
TI  - Effects of different head-neck positions on the larynges of ridden horses.
AB  - Hyperflexion, that is the strong deflection of the horse's head, poll and neck,
      is a prevalent training technique in equitation. Hyperflexion has come under
      criticism in recent years for being suspected of affecting the horses' well-being
      contrary to animal welfare. The goal of the present study is a comparison between
      the impacts of different poll-neck positions on findings in the upper respiratory
      tract of ridden horses. For this purpose, video recordings of the larynges of 14
      horses were taken using an overground endoscope. The videos were recorded at rest
      and during three different riding phases: firstly, in a stretching posture,
      secondly, in a working position and, thirdly, in hyperflexion. A comparison
      between the analyses of the working position and hyperflexion phases revealed a
      significant reduction in the laryngeal opening area (p = 0.001) with a value of
      8.2 +/- 5.0%. Furthermore, other parameters of the larynx evaluated also showed a
      significant diminishment. These changes did not correlate with the age of the
      horses or their level of education, and they were independent of the individual
      anatomical conditions of the poll-neck region. In summary, it can be stated that
      hyperflexion causes a considerable compression of the larynx. 

PMID- 24329610
TI  - Iron and infection in hemodialysis patients.
AB  - Intravenous iron is an important component of the treatment of anemia of end
      stage renal disease (ESRD), but it is biologically plausible that iron could
      increase the risk of infection through impairment of neutrophil and T-cell
      function and promotion of microbial growth. Any such increase in risk would be
      particularly important because infection is a significant cause of mortality and
      morbidity in dialysis patients. The overall evidence favors an association
      between iron and infection in hemodialysis patients, but the optimal iron
      management strategy to minimize infection risk has yet to be identified. There is
      a need for further research on this topic, particularly in light of increased
      utilization of intravenous iron following implementation of the bundled ESRD
      reimbursement system. 

PMID- 24329612
TI  - Molecular and social regulation of worker division of labour in fire ants.
AB  - Reproductive and worker division of labour (DOL) is a hallmark of social insect
      societies. Despite a long-standing interest in worker DOL, the molecular
      mechanisms regulating this process have only been investigated in detail in honey
      bees, and little is known about the regulatory mechanisms operating in other
      social insects. In the fire ant Solenopsis invicta, one of the most studied ant
      species, workers are permanently sterile and the tasks performed are modulated by
      the worker's internal state (age and size) and the outside environment (social
      environment), which potentially includes the effect of the queen presence through
      chemical communication via pheromones. However, the molecular mechanisms
      underpinning these processes are unknown. Using a whole-genome microarray
      platform, we characterized the molecular basis for worker DOL and we explored how
      a drastic change in the social environment (i.e. the sudden loss of the queen)
      affects global gene expression patterns of worker ants. We identified numerous
      genes differentially expressed between foraging and nonforaging workers in
      queenright colonies. With a few exceptions, these genes appear to be distinct
      from those involved in DOL in bees and wasps. Interestingly, after the queen was
      removed, foraging workers were no longer distinct from nonforaging workers at the
      transcriptomic level. Furthermore, few expression differences were detected
      between queenright and queenless workers when we did not consider the task
      performed. Thus, the social condition of the colony (queenless vs. queenright)
      appears to impact the molecular pathways underlying worker task performance,
      providing strong evidence for social regulation of DOL in S. invicta. 

PMID- 24329615
TI  - Mental health and immigration detention.

PMID- 24329613
TI  - A systematic approach to assess the strengths and limitations of cytomorphology
      in the diagnosis of the follicular variant of papillary thyroid carcinoma.
AB  - OBJECTIVE: To identify the most useful cytomorphological features of follicular
      variant of papillary thyroid carcinoma (FVPTC). METHODS: Fine needle aspiration
      cytological features of seven histologically proven FVPTCs were systematically
      evaluated in a blinded manner for various architectural, nuclear, cytoplasmic and
      background features with special reference to nuclear morphology. RESULTS: Most
      smears were moderate to highly cellular with clustered and/or repetitive
      microfollicles, rare macrofollicles and minimal thick gummy colloid. Six of seven
      cases showed significant nuclear crowding/overlapping. Fairly uniform
      nucleomegaly (mostly three to five times the size of a mature lymphocyte) of
      intact neoplastic cells and enlarged naked nuclei were prominent features in all
      seven cases, whereas enlarged ovoid nuclei were seen in two cases. Chromatin was
      fine to coarsely granular and evenly distributed. Occasional nuclear grooves
      (NGs) and intranuclear cytoplasmic inclusions (INCIs) were seen in five and three
      cases, respectively. This refined approach led to a precise diagnosis of FVPTC in
      six cases, which were earlier interpreted as various follicular lesions.
      Follicular hyperplasia was excluded by the absence of significant amounts of
      colloid and atretic naked nuclei, whilst the possibility of follicular adenoma or
      follicular carcinoma was excluded by the presence of one or more features
      suggestive of papillary thyroid carcinoma. CONCLUSIONS: Our study showed a high
      cell yield, microfollicular pattern, nuclear overcrowding/overlapping, scanty
      gummy colloid and enlarged naked nuclei as the most consistent features of FVPTC.
      Although inconsistent, features such as enlarged ovoid nuclei and syncytial
      clusters were complementary to the diagnosis in the absence of NGs and INCIs.

PMID- 24329616
TI  - Rural, urban: the real world for medical education.

PMID- 24329617
TI  - Treatment of snakebite in Australia: gathering the evidence.

PMID- 24329620
TI  - China and the organ trade.

PMID- 24329621
TI  - Suicide and self-harm prevention for people in immigration detention.

PMID- 24329622
TI  - Women Deliver 2013: taking a gender lens to the new global health and development
      agenda.

PMID- 24329623
TI  - How should we interpret hospital infection statistics?

PMID- 24329624
TI  - Reports indicate that changes are needed to close the gap for Indigenous health.

PMID- 24329625
TI  - Skin cancer detection by one click - are we any closer?

PMID- 24329626
TI  - Children and clandestine drug laboratories: the unseen victims.

PMID- 24329627
TI  - Could a scheme for licensing smokers work in Australia?

PMID- 24329628
TI  - Could a scheme for licensing smokers work in Australia?

PMID- 24329629
TI  - Publicly funded homebirth in Australia: a review of maternal and neonatal
      outcomes over 6 years.

PMID- 24329630
TI  - Publicly funded homebirth in Australia: a review of maternal and neonatal
      outcomes over 6 years.

PMID- 24329631
TI  - Publicly funded homebirth in Australia: a review of maternal and neonatal
      outcomes over 6 years.

PMID- 24329632
TI  - Birthweight and fasting glucose and insulin levels: results from the Aboriginal
      Birth Cohort Study.

PMID- 24329633
TI  - Birthweight and fasting glucose and insulin levels: results from the Aboriginal
      Birth Cohort Study.

PMID- 24329634
TI  - Using SMS technology to verify the safety of seasonal trivalent influenza vaccine
      for pregnant women in real time.

PMID- 24329635
TI  - Systematic postmarketing surveillance needed for misused psychoactive
      pharmaceutical drugs.

PMID- 24329636
TI  - Systematic postmarketing surveillance needed for misused psychoactive
      pharmaceutical drugs.

PMID- 24329637
TI  - Systematic postmarketing surveillance needed for misused psychoactive
      pharmaceutical drugs.

PMID- 24329638
TI  - An audit of the use of ondansetron in general medical patients.

PMID- 24329639
TI  - Inadvertent dispensing of Coumadin instead of Coversyl.

PMID- 24329640
TI  - Prevention of peripheral intravenous catheter-related bloodstream infections: the
      need for routine replacement.

PMID- 24329641
TI  - Prevention of peripheral intravenous catheter-related bloodstream infections: the
      need for routine replacement.

PMID- 24329642
TI  - Prevention of peripheral intravenous catheter-related bloodstream infections: the
      need for routine replacement.

PMID- 24329643
TI  - Time to reconsider steroid injections in the spine?

PMID- 24329644
TI  - Time to reconsider steroid injections in the spine?

PMID- 24329645
TI  - Students as teachers.

PMID- 24329646
TI  - Time to reconsider steroid injections in the spine?

PMID- 24329647
TI  - Students as teachers.

PMID- 24329648
TI  - Students as teachers.

PMID- 24329649
TI  - Students as teachers.

PMID- 24329650
TI  - Advising pregnant women to avoid alcohol.

PMID- 24329652
TI  - (Re)introducing medicinal cannabis.
AB  - * After considering extensive scientific and medical evidence, a New South Wales
      Legislative Council multiparty committee recommended that medicinal cannabis
      should lawfully be made available for selected-use pharmacotherapy. * The
      evidence indicates that cannabis has genuine medicinal utility in patients with
      certain neuropathic conditions, with acceptable levels of risk from mostly mild
      side effects. * The potential medical benefits of cannabis pharmacotherapy have
      largely been overlooked, with research and society's attention, in most parts of
      the world, being directed towards the hazards of its recreational use. * The NSW
      Government has since dismissed the unanimous and compassionate recommendations of
      their committee.

PMID- 24329653
TI  - Snakebite in Australia: a practical approach to diagnosis and treatment.
AB  - Snakebite is a potential medical emergency and must receive high-priority
      assessment and treatment, even in patients who initially appear well. Patients
      should be treated in hospitals with onsite laboratory facilities, appropriate
      antivenom stocks and a clinician capable of treating complications such as
      anaphylaxis. All patients with suspected snakebite should be admitted to a
      suitable clinical unit, such as an emergency short-stay unit, for at least 12
      hours after the bite. Serial blood testing (activated partial thromboplastin
      time, international normalised ratio and creatine kinase level) and neurological
      examinations should be done for all patients. Most snakebites will not result in
      significant envenoming and do not require antivenom. Antivenom should be
      administered as soon as there is evidence of envenoming. Evidence of systemic
      envenoming includes venom-induced consumption coagulopathy, sudden collapse,
      myotoxicity, neurotoxicity, thrombotic microangiopathy and renal impairment.
      Venomous snake groups each cause a characteristic clinical syndrome, which can be
      used in combination with local geographical distribution information to determine
      the probable snake involved and appropriate antivenom to use. The Snake Venom
      Detection Kit may assist in regions where the range of possible snakes is too
      broad to allow the use of monovalent antivenoms. When the snake identification
      remains unclear, two monovalent antivenoms (eg, brown snake and tiger snake
      antivenom) that cover possible snakes, or a polyvalent antivenom, can be used.
      One vial of the relevant antivenom is sufficient to bind all circulating venom.
      However, recovery may be delayed as many clinical and laboratory effects of venom
      are not immediately reversible. For expert advice on envenoming, contact the
      National Poisons Information Centre on 13 11 26.

PMID- 24329654
TI  - Carrying weapons and intent to harm among Victorian secondary school students in
      1999 and 2009.
AB  - OBJECTIVE: To examine comparable survey data across 10 years to assess whether
      rates of self-reported weapon carrying and intent to harm others have increased
      as suggested in reported trends in violent offences. DESIGN, SETTING AND
      PARTICIPANTS: Population-based surveys administered to Victorian secondary school
      students in 1999 (8984 students) and 2009 (10 273 students) attending government,
      Catholic and independent schools. MAIN OUTCOME MEASURES: Student self-reports of
      carrying a weapon and attacking someone with the intent to harm in the past 12
      months. RESULTS: In both surveys, about 15.0% of students reported carrying a
      weapon and about 7.0% reported attacking someone with intent to harm in the past
      12 months, with higher rates among boys than girls. There was no change over time
      in the rates of students carrying weapons or attacking someone with the intent to
      harm, after controlling for demographic variables. CONCLUSIONS: In contrast to
      media portrayals and reported trends in violent offences, rates of students
      carrying weapons and attacking others with intent to harm have not changed
      between 1999 and 2009. These findings underline the importance of having national
      population-based data to regularly monitor the rates of these and related
      behaviours among young Australians.

PMID- 24329655
TI  - Coping support factors among Australians affected by terrorism: 2002 Bali bombing
      survivors speak.
AB  - OBJECTIVES: To examine terrorism survivors' perceptions of factors likely to
      promote coping and recovery, and to determine whether coping supports vary
      according to demographic, physical and mental health, incident-exposure and
      bereavement variables. DESIGN, SETTING AND PARTICIPANTS: Individuals directly
      exposed to and/or bereaved by the 2002 Bali bombings and who had participated in
      a New South Wales Health therapeutic support program completed cross-sectional
      telephone interviews during July-November 2010. Spoken passages were categorised
      into coping support themes. Advocated supports were then examined by demographic,
      physical and mental health, incident-exposure and bereavement variables. MAIN
      OUTCOME MEASURES: Based on their experiences, respondents identified personal,
      social and service-related factors that they believed would optimally support
      future survivors of terrorism. RESULTS: Of the 81 people contacted, 55 (68%)
      participated, providing a total of 114 comments. Thirty-two respondents were
      women, and 54 had lost relatives or friends in the bombing. Mean age was 50 years
      (range, 20-73 years). Four meaningful coping support themes emerged, with
      excellent inter-rater reliability: professional help and counselling; social
      support; proactive government response and policy; and personal coping
      strategies. Women were significantly more likely to advocate the need for
      proactive government response (P = 0.03). Men were more likely to endorse the use
      of personal coping strategies (P < 0.01). Respondents diagnosed with a mental
      health condition since the bombings were significantly less likely to advocate
      social support processes (P = 0.04). CONCLUSIONS: Our findings highlight the
      perceived value of counselling-related services for terrorism-affected groups.
      Male survivors may benefit more from mental health interventions that initially
      build on problem-focused forms of coping, including brief education about
      reactions and periodic check-ups. Proactive government health and support
      services that allow simplified and longer-term access were consistently
      identified as priority areas.

PMID- 24329656
TI  - Use of Royal Darwin Hospital emergency department by immigration detainees in
      2011.
AB  - OBJECTIVE: To describe the number and nature of emergency department (ED)
      attendances by immigration detainees in Darwin, in the Northern Territory, over a
      12-month period. DESIGN AND SETTING: Retrospective observational study of
      immigration detainees attending the Royal Darwin Hospital ED during the 2011
      calendar year. MAIN OUTCOME MEASURES: Number of ED attendances and primary
      diagnoses. RESULTS: In 2011, there were 770 ED attendances by 518 individual
      detainees at Royal Darwin Hospital. Those who attended the ED had a mean (SD) age
      of 27.6 (12.2) years, and 112 of them (21.6%) were children. Most (413, 79.7%)
      were male, and Iran and Afghanistan were the two most common countries of birth.
      We estimate that 50.1% (95% CI, 47.0%-53.2%) of immigration detainees in Darwin
      (mean, 776 per month; total, 1034), attended the Royal Darwin Hospital ED at
      least once in 2011. The most common primary diagnosis was psychiatric problems
      (187 attendances, 24.3%), including self-harm (138 attendances, 17.9%).
      CONCLUSION: In 2011, asylum seekers in immigration detention in Darwin had a high
      prevalence of unmet health needs and substantial levels of psychiatric morbidity.
      The primary health care provided to them was inadequate.

PMID- 24329657
TI  - Medical graduates becoming rural doctors: rural background versus extended rural
      placement.
AB  - OBJECTIVES: To determine whether recruitment of rural students and uptake of
      extended rural placements are associated with students' expressed intentions to
      undertake rural internships and students' acceptance of rural internships after
      finishing medical school, and to compare any associations. DESIGN, SETTING AND
      PARTICIPANTS: Longitudinal study of three successive cohorts (commencing 2005,
      2006, 2007) of medical students in the Sydney Medical Program (SMP), University
      of Sydney, New South Wales, using responses to self-administered questionnaires
      upon entry to and exit from the Sydney Medical School and data recorded in rolls.
      MAIN OUTCOME MEASURES: Students' expressed intentions to undertake rural
      internships, and their acceptance of rural internships after finishing medical
      school. RESULTS: Data from 448 students were included. The proportion of students
      preferring a rural career dropped from 20.7% (79/382) to 12.5% (54/433) between
      entry into and exit from the SMP. A total of 98 students took extended rural
      placements. Ultimately, 8.1% (35/434) accepted a rural internship, although 14.5%
      (60/415) had indicated a first preference for a rural post. Students who had
      undertaken an extended rural placement were more than three times as likely as
      those with rural backgrounds to express a first preference for a rural internship
      (23.9% v 7.7%; chi(2) = 7.04; P = 0.008) and more than twice as likely to accept
      a rural internship (21.3% v 9.9%; chi(2) = 3.85; P = 0.05). CONCLUSION: For the
      three cohorts studied, rural clinical training through extended placements in
      rural clinical schools had a stronger association than rural background with a
      preference for, and acceptance of, rural internship.

PMID- 24329658
TI  - Four centuries of suicide in opera.
AB  - OBJECTIVE: To describe the depiction of completed suicide, non-fatal suicidal
      acts and suicidal thought in Western opera over the past four centuries. DESIGN
      AND SETTING: Examination of synopses all of the operas listed in a recent
      monograph covering a selection of operas written in the period 1607-2006. MAIN
      OUTCOME MEASURES: Frequency of completed suicides, non-fatal suicidal acts and
      suicidal thoughts over the entire 400-year period and in separate 100-year
      periods (1607-1706, 1707-1806, 1807-1906 and 1907-2006); circumstances of
      suicides; sex of the suicidal characters; and, for completed suicide, the method.
      RESULTS: There were 337 operas in total. In 112 (33%), there was completed
      suicide alone, non-fatal suicidal acts or suicidal thoughts alone, or both. There
      was at least one suicide in 74 operas (22%); female characters accounted for 56%
      of these. Non-fatal suicidal acts or suicidal thoughts were found in 48 operas
      (14%); male characters accounted for 57% of these. Suicide, non-fatal acts and
      suicidal thoughts always followed an undesirable event or situation. Cutting or
      stabbing was the most common method of suicide (26 cases). Other methods included
      poisoning (15 cases), drowning (10 cases), hanging (four cases), asphyxiation
      (four cases), "supernatural" methods (four cases), immolation (three cases),
      jumping from a height (two cases), shooting (one) and blunt trauma (one). Mass
      suicide occurred on two occasions. CONCLUSIONS: Over several centuries in opera,
      suicide has been frequently represented as an option when characters have been
      faced with a distressing event or situation. Historical fluctuations in the
      frequency of suicidal behaviour in opera may be explained by changes in attitudes
      towards suicide and its conceptualisation.

PMID- 24329659
TI  - Rural general practice placements: alignment with the Australian Curriculum
      Framework for Junior Doctors.
AB  - OBJECTIVES: To review the available literature regarding skills and competencies
      gained by junior doctors in rural and regional general practice placements and
      their alignment with the Australian Curriculum Framework for Junior Doctors
      (ACFJD). STUDY DESIGN: A comprehensive literature review using a three-phase
      process. Articles were initially identified from database searches in OvidSP and
      Scopus. Additional information was obtained after a hand search of contents pages
      from relevant journals and from reports, conference abstracts and grey
      literature. Documented skills and procedures were mapped against the competencies
      from the ACFJD. DATA SOURCES: We analysed 36 relevant articles written in English
      and published during 1997-2011. Articles referring to learning outcomes for
      junior doctors training with rural general practitioners were included. DATA
      SYNTHESIS: Evidence was available of the advantages of junior doctor rural
      general practice placements in gaining advanced skills in the areas of
      communication and professionalism, as well as developing autonomy in clinical
      management and decision making. Less evidence was available regarding exposure to
      particular clinical conditions and development of specific clinical skills.
      CONCLUSION: Rural and regional general practice placements for junior doctors are
      likely to comply with the ACFJD requirements and, further, provide excellent
      learning opportunities in several domains of the curriculum. However, there was
      little research published confirming learning outcomes for junior doctors in
      rural general practice settings.

PMID- 24329660
TI  - Tachycardia of unknown Origin.

PMID- 24329661
TI  - Paroplocephalus envenoming: a previously unrecognised highly venomous snake in
      Australia.

PMID- 24329662
TI  - Cane toads and bush tucker: starvation ketoacidosis in a bushwalker.

PMID- 24329663
TI  - Murra Mullangari - Pathways Alive and Well.

PMID- 24329664
TI  - A quack heard around the world.

PMID- 24329665
TI  - The power of 13.

PMID- 24329666
TI  - Students as teachers.

PMID- 24329673
TI  - The hobbit - an unexpected deficiency.
AB  - OBJECTIVE: Vitamin D has been proposed to have beneficial effects in a wide range
      of contexts. We investigate the hypothesis that vitamin D deficiency, caused by
      both aversion to sunlight and unwholesome diet, could also be a significant
      contributor to the triumph of good over evil in fantasy literature. DESIGN: Data
      on the dietary habits, moral attributes and martial prowess of various
      inhabitants of Middle Earth were systematically extracted from J R R Tolkien's
      novel The hobbit. MAIN OUTCOME MEASURES: Goodness and victoriousness of
      characters were scored with binary scales, and dietary intake and habitual sun
      exposure were used to calculate a vitamin D score (range, 0-4). RESULTS: The
      vitamin D score was significantly higher among the good and victorious characters
      (mean, 3.4; SD, 0.5) than the evil and defeated ones (mean, 0.2; SD, 0.4; P <
      0.001). CONCLUSION: Further work is needed to see if these pilot results can be
      extrapolated to other fantastic situations and whether randomised intervention
      trials need to be imagined.

PMID- 24329674
TI  - O come, all ye faithful: a study on church syncope.
AB  - OBJECTIVES: To determine the incidence of patients presenting to a major
      metropolitan hospital after experiencing syncope at church, and to compare their
      outcomes with those of patients experiencing syncope at other locations. DESIGN,
      SETTING AND PARTICIPANTS: A retrospective matched cohort study in which patients
      presenting with church syncope between July 2009 and June 2013 were compared with
      controls (patients presenting after syncope experienced elsewhere) matched by 5
      year age group and San Francisco Syncope Score. MAIN OUTCOME MEASURES: Admission
      to hospital was the primary outcome measure. Mortality, intensive care unit or
      coronary care unit admission, and length of stay in hospital were secondary
      outcome measures. RESULTS: There were 31 cases of church syncope during the study
      period, which were matched to 62 controls. The hospital admission rate among
      patients who experienced syncope in church was significantly lower than among
      controls (22.6% v 46.8%; P = 0.02). After adjusting for other variables
      significantly associated with admission to hospital, the church as a location for
      syncope was no longer significantly associated with hospital admission (odds
      ratio, 0.4; 95% CI, 0.1-1.1; P = 0.06). CONCLUSIONS: The number of patients
      presenting to hospital after church syncope was low; most had benign diagnoses
      and were discharged home from the emergency department. While syncope at church
      was associated with a lower rate of hospital admission, the church did not appear
      to offer any additional sanctuary when clinical risk profiles were taken into
      consideration.

PMID- 24329675
TI  - Are bald men more virile than their well thatched contemporaries?
AB  - OBJECTIVE: To test the popular assertion that bald men are more virile than their
      well thatched contemporaries DESIGN, PARTICIPANTS AND SETTING: Secondary analysis
      of data from a case-control study in a community setting between 1994 and 1997
      among men below the age of 70 years, using in-person interviews and
      categorisation of baldness, with subsequent completion of a questionnaire by the
      participant. We analysed risk factors for baldness using unconditional logistic
      regression. MAIN OUTCOME MEASURES: Baldness; history of ejaculations between the
      ages of 20 and 49 years; total number of sexual partners. RESULTS: There was no
      significant association between baldness and the frequency of ejaculations, but
      bald men were significantly less likely to have had more than four female sexual
      partners. CONCLUSIONS: In the population studied, bald men appear to be no more
      virile than their well thatched contemporaries.

PMID- 24329677
TI  - Harriet's hats.

PMID- 24329676
TI  - The effect of a gold coin fine on C-reactive protein test ordering in a tertiary
      referral emergency department.
AB  - OBJECTIVE: To examine the effect of an education campaign based around a gold
      coin fine on ordering of C-reactive protein (CRP) tests. DESIGN AND SETTING: A
      retrospective analysis of CRP test ordering before and after the intervention in
      the emergency department (ED) of a tertiary referral hospital in metropolitan
      Sydney that sees about 60,000 patients per annum. The date of the intervention -
      2 August 2013 - corresponded with Jeans for Genes Day. MAIN OUTCOME MEASURES:
      Number of CRP tests ordered in the ED. RESULTS: 1290 CRP tests were ordered
      before the intervention (1-31 July), and 394 were ordered after the intervention
      (2-31 August). This decrease in CRP test ordering was despite an increased number
      of ED presentations in August compared with July (5219 v 5497 presentations).
      This represented an absolute reduction in the rate of CRP test ordering of 17.6%
      (95% CI, 16.2%-18.9%; P < 0.001). CONCLUSION: The threat of a gold coin fine for
      ordering a CRP test, as part of a broader education campaign, significantly
      reduced the number of CRP tests ordered in a tertiary referral ED.

PMID- 24329678
TI  - The Da Vinci Code and the alphabet of research.

PMID- 24329679
TI  - Why I don't mind working nightshift anymore.

PMID- 24329681
TI  - Fundus autofluorescence imaging in multifocal choroiditis: beyond the spots.
AB  - PURPOSE: To describe fundus autofluorescence (FAF) imaging and its correlation to
      spectral-domain optical coherence tomography (SD-OCT) in retinal areas that
      appear clinically noninvolved in patients with multifocal choroiditis/punctate
      inner choroidopathy (MFC/PIC). METHODS: Six patients with MFC or PIC were
      evaluated during the disease course with multimodal imaging, which included
      fluorescein angiography, FAF imaging, indocyanine green angiography, and SD-OCT.
      RESULTS: Five patients had acute and/or scarred chorioretinal spots at
      presentation. Five patients had choroidal neovascularization. FAF imaging in all
      patients disclosed diffuse peripapillary and/or posterior-pole
      hyperautofluorescent plaques in areas that appeared clinically to be noninvolved.
      Corresponding SD-OCT scans revealed severe disruption of the inner segment/outer
      segment junction. Findings resolved with corticosteroid treatment Conclusions:
      FAF imaging of patients with MFC/PIC reveals extensive pathology beyond the
      clinically apparent spots. FAF findings highlight the areas of corresponding
      anatomic disruption of the photoreceptor-retinal pigment epithelium complex.

PMID- 24329680
TI  - Immunological monitoring of extracorporeal photopheresis after heart
      transplantation.
AB  - Extracorporeal photopheresis (ECP) has been used as a prophylactic and
      therapeutic option to avoid and treat rejection after heart transplantation
      (HTx). Tolerance-inducing effects of ECP such as up-regulation of regulatory T
      cells (T(regs)) are known, but specific effects of ECP on regulatory T cell
      (T(reg)) subsets and dendritic cells (DCs) are lacking. We analysed different
      subsets of T(regs) and DCs as well as the immune balance status during ECP
      treatment after HTx. Blood samples were collected from HTx patients treated with
      ECP for prophylaxis (n = 9) or from patients with histologically proven acute
      cellular rejection (ACR) of grade >= 1B (n = 9), as well as from control HTx
      patients without ECP (HTxC; n = 7). Subsets of T(regs) and DCs as well as
      different cytokine levels were analysed. Almost 80% of the HTx patients showed an
      effect to ECP treatment with an increase of T(regs) and plasmacytoid DCs (pDCs).
      The percentage of pDCs before ECP treatment was significantly higher in patients
      with no ECP effect (26.3% +/- 5.6%) compared to patients who showed an effect to
      ECP (9.8% +/- 10.2%; P = 0.011). Analysis of functional subsets of
      CD4+CD25(high)CD127(low) T(regs) showed that CD62L-, CD120b- and CD147-positive
      T(regs) did not differ between the groups. CD39-positive T(regs) increased during
      ECP treatment compared to HTxC. ECP-treated patients showed higher levels for T
      helper type 1 (Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx
      patients with rejection before ECP treatment compared to patients with
      prophylactic ECP treatment. We recommend a monitoring strategy that includes the
      quantification and analysis of T(regs), pDCs and the immune balance status before
      and up to 12 months after starting ECP.

PMID- 24329682
TI  - Inhibitory effects of deleted in liver cancer 1 gene on gallbladder cancer growth
      through induction of cell cycle arrest and apoptosis.
AB  - BACKGROUND AND AIM: The biological function of tumor suppressor deleted in liver
      cancer 1 (DLC1) has been investigated in several types of human cancer, but its
      role in gallbladder cancer (GBC) is yet to be determined. In this research, we
      conducted in vitro and in vivo analysis to evaluate the inhibitory activities of
      DLC1 gene against GBC growth. METHODS: DLC1 expression in GBC tissues and cell
      lines was examined by immunohistochemical staining, reverse transcription
      polymerase chain reaction, and Western blot assay. The in vitro and in vivo
      effects of ectopic DLC1 expression on cell growth were evaluated. In addition,
      the effects of ectopic DLC1 expression on cell cycle, apoptosis, and migration
      were also evaluated. The expressions of cell cycle-related and apoptosis-related
      proteins were examined. RESULTS: The downregulation of DLC1 expression was a
      common event in GBC tissues and cell lines. Restoration of DLC1 expression in GBC
      SD and NOZ cells significantly reduced cell proliferation, migration in vitro,
      and the ability of these cells to form tumors in vivo. Restoration of DLC1
      expression arrested GBC-SD and NOZ cells in G0/G1 phase through inducing p21 in a
      p53-independent manner. In addition, restoration of DLC1 expression induced
      extrinsic and intrinsic apoptotic pathway through promoting the expressions of
      Fas L/FADD, Bax, cytochrome c, cleaved caspase-8, -9, -3, and cleaved poly-(ADP
      ribose) polymerase and suppressing bcl-2 expression in GBC-SD and NOZ cells.
      CONCLUSIONS: Our findings suggested that dysregulated expression of DLC1 is
      involved in proliferation and invasion of GBC cells and may serve as a potential
      therapeutic target.

PMID- 24329683
TI  - Search for novel targets of the PII signal transduction protein in Bacteria
      identifies the BCCP component of acetyl-CoA carboxylase as a PII binding partner.
AB  - The PII family comprises a group of widely distributed signal transduction
      proteins. The archetypal function of PII is to regulate nitrogen metabolism in
      bacteria. As PII can sense a range of metabolic signals, it has been suggested
      that the number of metabolic pathways regulated by PII may be much greater than
      described in the literature. In order to provide experimental evidence for this
      hypothesis a PII protein affinity column was used to identify PII targets in
      Azospirillum brasilense. One of the PII partners identified was the biotin
      carboxyl carrier protein (BCCP), a component of the acetyl-CoA carboxylase which
      catalyses the committed step in fatty acid biosynthesis. As BCCP had been
      previously identified as a PII target in Arabidopsis thaliana we hypothesized
      that the PII -BCCP interaction would be conserved throughout Bacteria. In vitro
      experiments using purified proteins confirmed that the PII -BCCP interaction is
      conserved in Escherichia coli. The BCCP-PII interaction required MgATP and was
      dissociated by increasing 2-oxoglutarate. The interaction was modestly affected
      by the post-translational uridylylation status of PII ; however, it was
      completely dependent on the post-translational biotinylation of BCCP. 

PMID- 24329685
TI  - Identifying optimal parameters for quantification of changes in pelvic movement
      symmetry as a response to diagnostic analgesia in the hindlimbs of horses.
AB  - REASONS FOR PERFORMING STUDY: Subjective evaluation of the response to diagnostic
      analgesia of hindlimb lameness is influenced by expectation bias. Quantification
      of pelvic movement with inertial measurement units is possible, but it is unclear
      which measure of movement symmetry best reflects the changes seen after
      diagnostic analgesia. OBJECTIVES: To test our hypothesis that objective measures
      closely relating to those used for subjective visual lameness scoring
      (quantifying the difference between sacral upward or downward movement or between
      movement amplitudes of the left and right tubera coxae) would show the largest
      and most consistent response. STUDY DESIGN: Retrospective analysis of subjective
      and objective clinical lameness data. METHODS: Thirteen horses with hindlimb
      lameness underwent visual lameness scoring and independent gait assessment with
      inertial measurement units. Established objective measures were calculated and
      changes before/after diagnostic analgesia regressed against the change in
      lameness grade. Slopes of regression lines were calculated and confidence
      intervals assessed. RESULTS: All objective parameters showed variation between
      horses and across lameness grades. The following 3 measures documented a
      consistent increase in symmetry for each grade of change in lameness score:
      difference between sacral displacement minima; upward movement difference; and
      range of motion difference between the tubera coxae. CONCLUSIONS: Several pelvic
      parameters are suitable for objective quantification of changes after diagnostic
      analgesia in hindlimb-lame horses. A change of 9-13% per lameness grade can be
      expected. Upward movement of the tubera coxae is the most sensitive objective
      measure for quantifying a response to diagnostic analgesia. However, when
      assessed visually, this measure requires simultaneous focusing on pelvic and limb
      movements. Other parameters that show a similar response might be more easily
      perceived, requiring only assessment of tubera coxae range of motion or downward
      displacement of the sacrum without simultaneous focus on limb movement.

PMID- 24329686
TI  - What can I do with a doctoral degree in gerontology? Expanding your options.
AB  - An endless number of career trajectories are possible for gerontologists. With a
      growing aging population, our skills and areas of expertise are of high value to
      numerous industries. The purpose of this study is to describe the professional
      development and career trajectories of alumni of U.S. doctoral gerontology
      programs obtained through the Gerontology Education Longitudinal Study (GELS).
      Specifically, the authors examine how professional identification, doctoral
      program career preparation, and perception of job prospects affect alumni
      decisions to pursue "traditional" (i.e., academic) versus "nontraditional" (i.e.,
      non-academic) careers. Results from the GELS revealed a fairly even split in the
      alumni sample of careers in traditional and nontraditional settings. The decision
      to pursue a traditional versus nontraditional career was not significantly
      associated with personal identification, doctoral program career preparation, or
      perception of employment options. These results suggest that the skill set
      obtained in doctoral gerontology programs is useful and is in demand in a variety
      of careers; therefore, doctoral programs may want to consider tailoring training
      to meet students' future career goals in both academic and non-academic settings.

PMID- 24329687
TI  - A case of xanthoma disseminatum: evaluation and monitoring by 18F
      fluorodeoxyglucose positron emission tomography/computed tomography.
AB  - Xanthoma disseminatum (XD) is a rare benign histiocytic disorder with extensive
      mucocutaneous xanthomas that often involves other sites such as the central
      nervous system (CNS), respiratory tract and abdominal organs. Evaluation of the
      extent of disease is important because lesions in critical locations may increase
      morbidity and mortality. However, there are no well-established tools for the
      evaluation and monitoring of XD. Here, we report a case of XD in a 21-year-old
      male patient showing skin, mucous membrane, CNS and internal organ involvement.
      In this case, (18) F-fluorodeoxyglucose positron emission tomography/computed
      tomography was useful in detecting the extent of the disease and in estimating
      the therapeutic response. 

PMID- 24329689
TI  - Place avoidance tasks as tools in the behavioral neuroscience of learning and
      memory.
AB  - Spatial navigation comprises a widely-studied complex of animal behaviors. Its
      study offers many methodological advantages over other approaches, enabling
      assessment of a variety of experimental questions and the possibility to compare
      the results across different species. Spatial navigation in laboratory animals is
      often considered a model of higher human cognitive functions including
      declarative memory. Almost fifteen years ago, a novel dry-arena task for rodents
      was designed in our laboratory, originally named the place avoidance task, and
      later a modification of this approach was established and called active place
      avoidance task. It employs a continuously rotating arena, upon which animals are
      trained to avoid a stable sector defined according to room-frame coordinates.
      This review describes the development of the place avoidance tasks, evaluates the
      cognitive processes associated with performance and explores the application of
      place avoidance in the testing of spatial learning after neuropharmacological,
      lesion and other experimental manipulations. 

PMID- 24329688
TI  - Dominant CD4-dependent RNA-dependent RNA polymerase-specific T-cell responses in
      children acutely infected with human enterovirus 71 and healthy adult controls.
AB  - Human enterovirus 71 (EV71) is one of the major causes of hand, foot and mouth
      disease (HFMD), which leads to significant mortality in infected children. A
      prophylactic vaccine is urgently needed. However, little is known about the
      protective T-cell immunity in individuals infected with the EV71 virus. In this
      study, we performed a comprehensive ex vivo interferon-gamma ELISPOT analysis in
      31 children infected with EV71 as well as in 40 healthy adult controls of the
      CD4(+) and CD8(+) T-cell responses to overlapping peptides spanning the VP1
      structural protein and RNA-dependent RNA polymerase (RdRp) non-structural
      protein. EV71-specific CD4 T-cell responses were detected in most of the acute
      patients and were mostly CD4-dependent RdRp-specific responses. CD8-dependent VP1
      and RdRp-specific responses were also detected in a small proportion of recently
      infected children. There was no significant association between the strength of
      the T-cell responses and disease severity observed during the acute EV71
      infection phase. Interestingly, an RdRp-specific, but no VP1-specific, CD4
      dependent T-cell response was detected in 30% of the adult controls, and no T
      cell responses were detected in healthy children. In addition, 24 individual
      peptides containing potential T-cell epitope regions were identified. The data
      suggest that CD4-dependent RdRp-specific T-cell responses may play an important
      role in protective immunity, and the epitopes identified in this study should
      provide valuable information for future therapeutic and prophylactic vaccine
      design as well as basic research. 

PMID- 24329690
TI  - Proconvulsant action of two GABA(B) receptor antagonists is age-dependent.
AB  - Antagonists of GABA(B) receptors are expected to have proconvulsant action also
      in developing brain. Two antagonists (CGP55845 and CGP46381) were tested in a
      model of cortical epileptic afterdischarges (ADs) in 12-, 18- and 25-day-old rat
      pups with implanted electrodes. CGP55845 was dissolved in dimethylsulfoxide and
      the results demonstrated marked proconvulsant action of this solvent which masked
      possible action of the antagonist. Water soluble antagonist CGP46381 led to
      marked potentiation of ADs in 12-day-old animals, its action decreased with age,
      it was negligible in 25-day-old rats. Our results demonstrated important
      inhibitory role of GABA(B) receptors at very early stages of maturation. 

PMID- 24329691
TI  - Daily profile of glut1 and glut4 expression in tissues inside and outside the
      blood-brain barrier in control and streptozotocin-treated rats.
AB  - Glucose is molecule usually studied in relation to metabolism. Except for this
      traditional view, it is known that under certain conditions glucose can serve as
      a signal molecule for the circadian system. The circadian system is entrained by
      relevant synchronizing cues that can be tissue-dependent. Central oscillator is
      synchronized mainly by light-dark cycle, while peripheral oscillators can be
      entrained by food intake. Glucose transport in the organism is controlled by
      insulin dependent and independent mechanism. Therefore, we employed
      streptozotocin-induced diabetes to elucidate the influence of metabolic changes
      on glucose transporter (glut1, glut4) 24-h expression profile in peripheral
      oscillators in tissues, inside (frontal cortex, cerebellum) and outside (heart)
      the blood-brain barrier. Diabetes was induced by streptozotocin injection.
      Seventeen days later, sampling was performed during a 24-h cycle. Gene expression
      was measured using real-time PCR. We observed down-regulation of glut1 and glut4
      expression in the heart of diabetic rats. The expression of glut1 and glut4 in
      brain areas was not down-regulated, however, we observed trend to phase advance
      in glut1 expression in the cerebellum. These results may indicate higher glucose
      levels in diabetic brain, which might influence regulation of clock gene
      expression in different manner in brain compared to periphery. 

PMID- 24329692
TI  - Repetitive transcranial magnetic stimulation in the treatment of chronic
      orofacial pain.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is non-invasive
      neuromodulation method. We applied rTMS for the treatment of farmacoresistant
      chronic orofacial pain. We compared the effect of 10 Hz and 20 Hz stimulation.
      The study included 23 patients for 20 Hz stimulation and 36 patients for 10 Hz
      stimulation with pharmacotherapy resistant chronic facial pain aged 33-65 years
      with pain duration of at least 6 months. Monitoring of treatment effects was
      performed within 15 minutes of each rTMS application (days 1-5) and finally
      stimulation (active vs. sham coil). If compared with data with 10 Hz rTMS study
      (n=36) and with 20 Hz rTMS (n=23) trials using a parallel design. Only the
      results obtained in a series of five rTMS treatments in the first step (active
      n=24, sham n=12), that 20 Hz frequency rTMS using a higher intensity (95 % of
      motor threshold) to be equally effective relative to VAS (Visual analogue scale)
      and QST (quantitative sensory testing). In conclusions, the better results with
      the relief of orofacial pain were obtained with 20 Hz stimulation if compared
      with 10 Hz stimulation. It was proved with subjective (VAS) and objective
      evaluation (QST). rTMS can be used in the treatment of chronic intractable pain. 

PMID- 24329693
TI  - Effect of captopril and melatonin on fibrotic rebuilding of the aorta in 24 hour
      light-induced hypertension.
AB  - Chronic continuous light exposure leads to melatonin deficiency along with
      complex neurohumoral activation resulting in hypertension development in rats.
      The aim of this study was to show, whether continuous light induces fibrotic
      rebuilding of the aorta and whether the treatment with melatonin or angiotensin
      converting enzyme inhibitor captopril can prevent these potential alterations. In
      a six-week experiment, 3-month-old Wistar rats were divided into 4 groups (ten
      per group): controls, rats exposed to continuous light, exposed to continuous
      light plus treated with captopril (100 mg/kg/24 h) and exposed to continuous
      light plus treated with melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP)
      and collagen type I and III in the media of thoracic aorta were measured.
      Continuous light induced hypertension and fibrotic rebuilding of the aorta in
      terms of enhancement of collagen I and III concentration in the aortic media.
      Both captopril and melatonin prevented SBP rise and reduced collagen III
      concentration in the aorta. However, only melatonin reduced collagen I and the
      sum of collagen I and III in the aortic tissue. We conclude that in continuous
      light-induced hypertension, administration of melatonin, along with SBP
      reduction, decreases collagen I and III concentration in the aorta. It is
      suggested that antifibrotic effect of melatonin may reduce the stiffness of the
      aorta and small arteries and beneficially influence the nature of the pulse wave
      and peripheral vascular resistance. 

PMID- 24329694
TI  - Effect of reoxygenation on the electrical stability of the rat heart in vivo: a
      chronobiological study.
AB  - Reoxygenation following hypoxic episodes can increase the risk for the
      development of ventricular arrhythmias, which, in addition to circadian aspects
      of reoxygenation arrhythmias has not been studied extensively. The aim of the
      present study was to evaluate circadian changes in the electrical stability of
      the rat heart during reoxygenation following a hypoventilatory episode. The
      electrical stability of the heart, defined in the present study as the
      ventricular arrhythmia threshold (VAT), was measured at 3 h intervals at clock
      times 09:00, 12:00, 15:00, 18:00, 21:00, 24:00, 03:00, 06:00 and 09:00 during 20
      min hypoventilation (20 breaths/min, tidal volume = 0.5 ml/100 g body weight
      [n=17]) and subsequent 20 min reoxygenation (50 breaths/min, tidal volume = 1
      ml/100 g body weight [n=4]) intervals. The experiments were performed using
      pentobarbital-anesthetized (40 mg/kg intraperitoneally) female Wistar rats that
      first underwent a four-week adaptation to a 12 h light:12 h dark regimen.
      Detailed analysis showed that circadian VATs changed to biphasic rhythms at 10
      min of hypoventilation. The VAT circadian rhythms were observed immediately
      following the commencement of reoxygenation, with the highest values measured
      between 12:00 and 15:00, and the lowest values between 24:00 and 03:00. These
      results suggest that myocardial vulnerability is dependent on the light:dark
      cycle and characteristics of pulmonary ventilation. 

PMID- 24329695
TI  - Upregulation of genes involved in cardiac metabolism enhances myocardial
      resistance to ischemia/reperfusion in the rat heart.
AB  - Genes encoding enzymes involved in fatty acids (FA) and glucose oxidation are
      transcriptionally regulated by peroxisome proliferator-activated receptors
      (PPAR), members of the nuclear receptor superfamily. Under conditions associated
      with O(2) deficiency, PPAR-alpha modulates substrate switch (between FA and
      glucose) aimed at the adequate energy production to maintain basic cardiac
      function. Both, positive and negative effects of PPAR-alpha activation on
      myocardial ischemia/reperfusion (I/R) injury have been reported. Moreover, the
      role of PPAR-mediated metabolic shifts in cardioprotective mechanisms of
      preconditioning (PC) is relatively less investigated. We explored the effects of
      PPAR-alpha upregulation mimicking a delayed "second window" of PC on I/R injury
      in the rat heart and potential downstream mechanisms involved. Pretreatment of
      rats with PPAR-alpha agonist WY-14643 (WY, 1 mg/kg, i.p.) 24 h prior to I/R
      reduced post-ischemic stunning, arrhythmias and the extent of lethal injury
      (infarct size) and apoptosis (caspase-3 expression) in isolated hearts exposed to
      30-min global ischemia and 2-h reperfusion. Protection was associated with
      remarkably increased expression of PPAR-alpha target genes promoting FA
      utilization (medium-chain acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase-4
      and carnitine palmitoyltransferase I) and reduced expression of glucose
      transporter GLUT-4 responsible for glucose transport and metabolism. In addition,
      enhanced Akt phosphorylation and protein levels of eNOS, in conjunction with
      blunting of cardioprotection by NOS inhibitor L-NAME, were observed in the WY
      treated hearts. CONCLUSIONS: upregulation of PPAR-alpha target metabolic genes
      involved in FA oxidation may underlie a delayed phase PC-like protection in the
      rat heart. Potential non-genomic effects of PPAR-alpha-mediated cardioprotection
      may involve activation of prosurvival PI3K/Akt pathway and its downstream targets
      such as eNOS and subsequently reduced apoptosis.

PMID- 24329696
TI  - Estrogen can modulate menopausal women's heart rate variability.
AB  - The aim of our study was to compare the responses of heart rate variability (HRV)
      with two different types of hormonal substitution therapy (HT) in post-menopausal
      women (cross-sectional study) and to reveal an effect of HT shortly after
      beginning of its administration (follow-up study). To elucidate the influence of
      menopause and effects of different protocols of a HT on autonomic control of
      heart rate, we evaluated the heart rate variability (HRV) in 5 groups:
      premenopausal women (n=140), postmenopausal women without HT (n=360), women on HT
      with conjugated estrogen only (n=168), women on continuous combined estrogen
      progesterone HT (n=117), and men (n=140). Frequency-domain of short-term
      stationary R-R intervals was performed to evaluate the total variance, low
      frequency power (LF; 0.04-0.15 Hz), high frequency power (HF; 0.15-0.40 Hz),
      portion of low frequency power (LF%) and ratio of LF to HF (LF/HF). Significantly
      lower portion of the LF was found in premenopausal women [46.9 (+/-2.7) nu] when
      compared to untreated postmenopausal women [54.3 (+/-2.9) nu] and men [55.2 (+/
      3.0) nu]. Treatment by estrogen only was proved to decrease the LF% [40.1 (+/
      2.1) nu] while no effect on HRV was observed in women treated with combination of
      estrogen and progesterone [57.2 (+/-3.1) nu]. Also the HF was lower in
      postmenopausal women [4.16 (+/-0.16) ms(2)] than in premenopausal women [4.79 (+/
      0.22) ms(2)] and women treated with estrogen only [4.98 (+/-0.25) ms(2)] while in
      women treated with combined hormonal therapy the average value [3.99 (+/-0.21)
      ms(2)] did not significantly differ from that of untreated postmenopausal women.
      The follow-up study also proved increase of high frequency power already after
      two months of estrogen substitution therapy [4.86 (+/-0.14) ms(2) vs. 4.19 (+/
      0.15) ms(2)]. These results suggest that higher vagal modulation of heart rate
      that seems typical for younger women becomes after menopause similar to that of
      men. We also proved a positive shift of HRV parameters toward more beneficial
      values as for a cardiovascular risk in postmenopausal women treated with
      estrogens but not in those treated by combined estrogen - progesterone
      substitution therapy. 

PMID- 24329697
TI  - Pig model of pulmonary embolism: where is the hemodynamic break point?
AB  - Early recognition of collapsing hemodynamics in pulmonary embolism is necessary
      to avoid cardiac arrest using aggressive medical therapy or mechanical cardiac
      support. The aim of the study was to identify the maximal acute hemodynamic
      compensatory steady state. Overall, 40 dynamic obstructions of pulmonary artery
      were performed and hemodynamic data were collected. Occlusion of only left or
      right pulmonary artery did not lead to the hemodynamic collapse. When gradually
      obstructing the bifurcation, the right ventricle end-diastolic area expanded
      proportionally to pulmonary artery mean pressure from 11.6 (10.1, 14.1) to 17.8
      (16.1, 18.8) cm(2) (p<0.0001) and pulmonary artery mean pressure increased from
      22 (20, 24) to 44 (41, 47) mmHg (p<0.0001) at the point of maximal hemodynamic
      compensatory steady state. Similarly, mean arterial pressure decreased from 96
      (87, 101) to 60 (53, 78) mmHg (p<0.0001), central venous pressure increased from
      4 (4, 5) to 7 (6, 8) mmHg (p<0.0001), heart rate increased from 92 (88, 97) to
      147 (122, 165) /min (p<0.0001), continuous cardiac output dropped from 5.2 (4.7,
      5.8) to 4.3 (3.7, 5.0) l/min (p=0.0023), modified shock index increased from 0.99
      (0.81, 1.10) to 2.31 (1.99, 2.72), p<0.0001. In conclusion, instead of continuous
      cardiac output all of the analyzed parameters can sensitively determine the
      individual maximal compensatory response to obstructive shock. We assume their
      monitoring can be used to predict the critical phase of the hemodynamic status in
      routine practice. 

PMID- 24329698
TI  - Protective effect of captopril, olmesartan, melatonin and compound 21 on
      doxorubicin-induced nephrotoxicity in rats.
AB  - Chronic kidney disease (CKD) represents a serious public health problem with
      increasing prevalence and novel approaches to renal protection are continuously
      under investigation. The aim of this study was to compare the effect of melatonin
      and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin
      converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker
      olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month
      old male Wistar rats (12 per group) were treated for four weeks. The first group
      served as a control. The remaining groups were injected with a single dose of
      doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or
      captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10
      mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the
      blood pressure and the level of oxidative stress were enhanced along with reduced
      glomerular density and increased glomerular size. Captopril, olmesartan and
      melatonin prevented the doxorubicin-induced increase in systolic blood pressure.
      All four substances significantly diminished the level of oxidative burden and
      prevented the reduction of glomerular density and modestly prevented the increase
      of glomerular size. We conclude that captopril, olmesartan, melatonin and C21
      exerted a similar level of renoprotective effects in doxorubicin-induced
      nephrotoxicity. 

PMID- 24329699
TI  - Budesonide added to modified porcine surfactant Curosurf may additionally improve
      the lung functions in meconium aspiration syndrome.
AB  - Severe meconium aspiration syndrome (MAS) in newborns is often treated by
      exogenous surfactant. Because its efficacy is reduced by meconium-induced
      inflammation, glucocorticoid budesonide was added into surfactant preparation
      Curosurf to enhance efficacy of the surfactant therapy in experimental model of
      MAS. Oxygen-ventilated rabbits were intratracheally given meconium (25 mg/ml, 4
      ml/kg) to induce respiratory failure. Thirty minutes later, animals were treated
      by intratracheal budesonide (0.25 mg/kg) or surfactant lung lavage (10 ml/kg, 5
      mg phospholipids/ml) repeated twice, followed by undiluted Curosurf (100 mg
      phospholipids/kg) or by the above mentioned surfactant treatment with the last
      surfactant dose fortified with budesonide (0.25 mg/kg) or were untreated. Animals
      were ventilated for additional 5 hours and respiratory parameters were measured
      regularly. After sacrificing animals, wet-dry lung weight ratio was evaluated and
      plasma levels of interleukins (IL)-1beta, -6, -8, and TNF-alpha were measured by
      ELISA method. Efficacy of the given therapies to enhance lung functions and to
      diminish lung edema formation and inflammation increased from budesonide-only and
      surfactant-only therapy to surfactant+budesonide therapy. Combined therapy
      improved gas exchange from 30 min of administration, and showed a longer-lasting
      effect than surfactant-only therapy. In conclusions, budesonide additionally
      improved the effects of exogenous surfactant in experimental MAS. 

PMID- 24329700
TI  - Lower omega-3 index is a marker of increased propensity of hypertensive rat heart
      to malignant arrhythmias.
AB  - Polyunsaturated omega-3 fatty acids (omega-3 PUFA) are important components of
      cell membrane affecting its function and their deficiency is deleterious to
      health. We have previously shown that spontaneously hypertensive rats (SHR) are
      prone to life-threatening arrhythmias that are reduced by omega-3 PUFA intake.
      Purpose of this study was to explore plasma and red blood cells (RBC) profile of
      omega-3 and omega-6 PUFA as well as to determine omega-3 index, a risk factor for
      sudden cardiac death, in aged SHR and the effect of omega-3 PUFA intake. Male and
      female 12-month-old SHR and age-matched Wistar rats fed with omega-3 PUFA (200
      mg/kg BW/day/2 month) were compared with untreated rats. Composition of omega-3
      PUFA: alpha linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) as well as omega-6 PUFA: linoleic acid and arachidonic acid was analyzed by
      gas chromatography. Results showed sex- and strain-related differences of basal
      omega-3 and omega-6 PUFA levels in plasma and RBC as well as in response to omega
      3 PUFA intake. Comparing to Wistar rats omega-3 index, expressed as a percentage
      of EPA+DHA of total fatty acids, was lower in SHR and it increased due to
      consumption of omega-3 PUFA. Findings support our hypothesis that lower omega-3
      index may be also a marker of increased propensity of the hypertensive rat heart
      to malignant arrhythmias. 

PMID- 24329701
TI  - NMDA and AMPA receptors: development and status epilepticus.
AB  - Glutamate is the main excitatory neurotransmitter in the brain and ionotropic
      glutamate receptors mediate the majority of excitatory neurotransmission
      (Dingeldine et al. 1999). The high level of glutamatergic excitation allows the
      neonatal brain (the 2(nd) postnatal week in rat) to develop quickly but it also
      makes it highly prone to age-specific seizures that can cause lifelong
      neurological and cognitive disability (Haut et al. 2004). There are three types
      of ionotropic glutamate receptors (ligand-gated ion channels) named according to
      their prototypic agonists: N-methyl-D-aspartate (NMDA), 2-amino-3-(3-hydroxy-5
      methyl-isoxazol-4-yl) propanoic acid (AMPA) and kainate (KA). During early stages
      of postnatal development glutamate receptors of NMDA and AMPA type undergo
      intensive functional changes owing to modifications in their subunit composition
      (Carter et al. 1988, Watanabe et al. 1992, Monyer et al. 1994, Wenzel et al.
      1997, Sun et al. 1998, Lilliu et al. 2001, Kumar et al. 2002, Matsuda et al.
      2002, Wee et al. 2008, Henson et al. 2010, Pachernegg et al. 2012, Paoletti et
      al. 2013). Participation and role of these receptors in mechanisms of seizures
      and epilepsy became one of the main targets of intensive investigation (De Sarro
      et al. 2005, Di Maio et al. 2012, Rektor 2013). LiCl/Pilocarpine (LiCl/Pilo)
      induced status epilepticus is a model of severe seizures resulting in development
      temporal lobe epilepsy (TLE). This review will consider developmental changes and
      contribution of NMDA and AMPA receptors in LiCl/Pilo model of status epilepticus
      in immature rats. 

PMID- 24329702
TI  - Oxidative stress in immature brain following experimentally-induced seizures.
AB  - The existing data indicate that status epilepticus (SE) induced in immature
      animals is associated with oxidative stress and mitochondrial dysfunction. This
      has been demonstrated using two models of SE, induced by substances with a
      different mechanism of action (DL-homocysteic acid and 4-aminopyridine) which
      suggests that the findings are not model-dependent but they reflect more general
      phenomenon. Oxidative stress occurring in immature brain during and following
      seizures is apparently due to both the increased free radicals production and the
      limited antioxidant defense. Pronounced inhibition of mitochondrial complex I in
      immature brain was demonstrated not only during the acute phase of SE, but it
      persisted during long periods of survival, corresponding to the development of
      spontaneous seizures (epileptogenesis). The findings suggest that oxidative
      modification is most likely responsible for the sustained deficiency of complex I
      activity. It can be assumed that the substances with antioxidant properties
      combined with conventional therapies might provide a beneficial effect in
      treatment of epilepsy. 

PMID- 24329703
TI  - Experimental evaluation of the cardiac rhythm originating in myocardial sleeves
      of pulmonary veins using a monophasic action potential.
AB  - Spontaneous depolarization similar to that from the sinus node was documented
      from the myocardial sleeves of pulmonary veins (PV) after isolation procedures.
      It was then hypothesized that sinus node-like tissue is present in the PVs of
      humans. Based on a number of features, the myocardium of myocardial sleeves (MS)
      is highly arrhythmogenic. Membrane potentials originating from MS are invariably
      recordable at the PVs ostia in patients with atrial fibrillation (AF) and delayed
      conduction around the PVs ostia may play a role in re-entry process responsible
      for the initiation and maintenance of AF. Diagnostic and therapeutic evidence of
      premature atrial beats induced in MS of PVs and resulting in launch of AF was
      detected by 3D electroanatomic method of monophasic action potential (MAP). MAP
      recording plays an important role in a direct view of human myocardial
      electrophysiology under both physiological and pathological conditions. Its
      crucial importance lies in the fact that it enables the study of the action
      potential of myocardial cell in vivo and, therefore, the study of the dynamic
      relation of this potential with all the organism variables. The knowledge of
      pathological MAPs from PV myocardial sleeves can help us to confirm a diagnosis
      when finding the similar action potential morphology. MAP can be also used to
      evaluate the therapeutic efficiency of vagal nerves suppression, radiofrequency
      ablation or other treatment procedures in PVs myocardial sleeves as well as for
      post-treatment following up. 

PMID- 24329704
TI  - Effect of an inhibitor of neuronal nitric oxide synthase 7-nitroindazole on
      cerebral hemodynamic response and brain excitability in urethane-anesthetized
      rats.
AB  - The role of neuronal nitric oxide synthase (nNOS) in the pathophysiology of
      epilepsy and seizures remains disputable. One of the reasons why results from the
      acute in vivo studies display controversies might be the effect on the regulation
      of cerebral blood flow (CBF) during pharmacologically induced alterations of NO
      system. We examined neurovascular coupling in the rat sensorimotor cortex in
      response to transcallosal stimulation under nNOS inhibition by 7-nitroindazole (7
      NI). Adult Wistar rats were anesthetized with urethane and epidural silver EEG
      electrodes were implanted over sensorimotor cortices. Regional CBF was measured
      by Laser Doppler Flowmetry (LDF). We catheterized a common carotid artery to
      measure arterial blood pressure (BP). 7-NI did not significantly affect blood
      pressure and heart rate. Electrophysiological recordings of evoked potentials
      (EPs) revealed no effect on their amplitude, rhythmic potentiation or depression
      of EPs. Transcallosal stimulation of the contralateral cortex induced a frequency
      dependent rise in CBF. Although 7-NI did not significantly affect basal CBF and
      cortical excitability, hemodynamic responses to the transcallosal stimulation
      were diminished implicating a role of nNOS in neurovascular coupling. Urethane
      anesthesia is suitable for future epileptological experiments. Our findings
      demonstrate that NO contributes to the hemodynamic response during brain
      activation. 

PMID- 24329705
TI  - Oxidative stress induced by epileptic seizure and its attenuation by melatonin.
AB  - An epileptic seizure and postictal period in addition to well-known features are
      also characterized by massive consumption of energy. This is thought to lead to
      oxidative stress and increased generation of free radicals, which is reflected by
      increased levels of oxidative products. Our previous work described the
      neuroprotective effects of melatonin in preventing cognitive worsening after a
      single epileptic seizure. This work was aimed on direct measurement of free
      radicals in brain tissue using the EPR method 1, 15 and 60 minutes after seizure.
      The measurement was performed in adult male Wistar rats at the mentioned
      intervals after a single tonic-clonic seizure induced by flurothyl. In comparison
      to control animals there was a significant increase in hydroxyl and nitroxyl
      radicals 60 minutes after the seizure. The levels of hydroxyl radicals were
      significantly lower in animals that received melatonin 60 minutes before seizure
      induction compared to animals without preventive treatment. Therefore, melatonin
      affected the generation of the measured free radicals differently. An important
      finding was the delayed increase in free radicals after a single seizure in the
      later phases of recovery. 

PMID- 24329706
TI  - Both water intoxication and osmotic BBB disruption increase brain water content
      in rats.
AB  - Our previous experiments revealed that water intoxication and osmotic BBB
      disruption in the rat allow penetration of high-molecular substances into the
      brain and that resulting changes in the internal environment of the CNS lead to
      pathological development, such as the loss of integrity of myelin. The aim of the
      present study was to determine whether the previously described phenomena are
      associated with increased water content in the brain. To answer the question
      following methods were used: a) water intoxication: intraperitoneal
      administration of distilled water, b) osmotic BBB disruption: application of
      mannitol (20 %) selectively into the internal carotid artery, c) brain wet weight
      was measured after decapitation, and subsequently (after six days in thermostat
      set at 86  degrees C) the dry weight were estimated d) in animals with 20 % and
      30 % hyperhydration the degree of myelin deterioration was estimated e) animal
      locomotor activity was tested by continuous behavior tracking and analysis. Brain
      water content after water intoxication and following the administration of
      mannitol was higher than in the control group. Different degrees of
      hyperhydration led to different levels of brain water content and to different
      degrees of myelin impairment. Hyperhydration corresponding to 20 % of the body
      weight brought about lower locomotor activity. Increased water content in the
      brain after the BBB osmotic disruption is surprising because this method is
      frequently used in the clinical practice. 

PMID- 24329707
TI  - Fast and delayed locomotor response to acute high-dose nicotine administration in
      adult male rats.
AB  - The aim of the present study was to compare the immediate and delayed locomotor
      response to high-dose nicotine (NIC) administration in rats. The vertical and
      horizontal activity of behavior in adult male rats exposed to 1 mg/kg NIC or
      saline (SAL) were tested in a Laboras apparatus for one hour after drug
      application. Animals were then returned to their cages and housed for another
      seven days. After this period all animals were placed in Laboras again and their
      behavioral pattern was retested for another period of one hour (delayed
      response). Horizontal activity: immediately after nicotine administration animal
      were less mobile (first 2-minutes interval), when compared with controls. The
      immobilization effect of nicotine disappeared within 4 minutes and during whole
      first 10-minutes interval time spent by locomotion did not differ from controls.
      Locomotion activity of animals treated with nicotine increased robustly in
      following 10 minutes and remained significantly higher in 2nd, 3rd and 5th 10
      minutes interval. Vertical activity: Rearing frequency was significantly lowered
      by NIC administration in first two minutes of the experiment and the same was
      found when the duration of rearing was analyzed. Lower rearing intensity of NIC
      treated animals disappeared in 4 minutes and was finally higher during whole test
      session as compared with controls. When duration of rearing was analyzed it was
      significantly longer in NIC treated animals. In majority of observed behavioral
      aspects there were no differences between NIC treated rats and controls seven
      days after NIC or SAL treatment. Our results reflect effect of NIC and we
      conclude that NIC significantly influences behavior of experimental animals. 

PMID- 24329708
TI  - Effect of methamphetamine on cognitive functions of adult female rats prenatally
      exposed to the same drug.
AB  - The aim of this study was to investigate the effect of prenatal methamphetamine
      (MA) exposure and application of the same drug in adulthood on cognitive
      functions of adult female rats. Animals were prenatally exposed to MA (5 mg/kg)
      or saline (control group). The cognitive function was tested as ability of
      spatial learning in the Morris Water Maze (MWM). Each day of the experiment
      animals received an injection of MA (1 mg/kg) or saline. Our results demonstrated
      that prenatal MA exposure did not affect the latency to reach the hidden platform
      or the distance traveled during the Place Navigation Test; however, the speed of
      swimming was increased in prenatally MA-exposed rats compared to controls
      regardless of the treatment in adulthood. MA treatment in adulthood increased the
      latency and distance when compared to controls regardless of the prenatal
      exposure. Neither prenatal exposure, nor treatment in adulthood affected memory
      retrieval. As far as the estrous cycle is concerned, our results showed that
      prenatally MA-exposed females in proestrus/estrus swam faster than females in
      diestrus. This effect of estrous cycle was not apparent in control females. In
      conclusion, our results indicate that postnatal, but not prenatal exposure to MA
      affects learning of adult female rats. 

PMID- 24329709
TI  - Gender differences in the effect of prenatal methamphetamine exposure and
      challenge dose of other drugs on behavior of adult rats.
AB  - The aim of the present study was to compare the response to acute application of
      several drugs in adult male and female rats prenatally exposed to methamphetamine
      (MA). Spontaneous locomotor activity and exploratory behavior of adult male and
      female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras
      apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug
      [amphetamine - 5 mg/kg; cocaine - 5 mg/kg; MDMA (3,4
      methylenedioxymethamphetamine) - 5 mg/kg; morphine - 5 mg/kg; THC (delta9
      tetrahydrocannabinol) - 2 mg/kg] or saline was injected prior to testing. Our
      data demonstrate that prenatal MA exposure did not affect behavior in male rats
      with cocaine or morphine treatment, but increased locomotion and exploration in
      females. Application of amphetamine and MDMA in adulthood increased activity in
      both sexes, while cocaine and THC only in female rats. Morphine, on the other
      hand, decreased the activity in the Laboras test in both sexes. As far as sex and
      estrous cycle is concerned, the present study shows that males were generally
      less active than females and also females in proestrus-estrus phase of the
      estrous cycle were more active than females in diestrus. In conclusion, the
      present study shows that the prenatal MA exposure does not induce general
      sensitization but affects the sensitivity to drugs dependently to mechanism of
      drug action and with respect to gonadal hormones. 

PMID- 24329710
TI  - An exploration of pregnant teenagers' views of the future and their decisions to
      continue or terminate their pregnancy: implications for nursing care.
AB  - AIMS AND OBJECTIVES: To explore teenagers' views of the future in relation to
      their choices to continue or terminate pregnancy. BACKGROUND: Despite recent
      decreases in the numbers of teenage pregnancies, across the world, the teenage
      pregnancy rate remains high. Consideration of views of the future (future
      orientation) appears to play an important part in teenage girls' decisions to
      continue with pregnancy. To date, no study has explored this in teenage pregnant
      girls at the time they make their decision to continue with or terminate their
      pregnancy. DESIGN: Cross-sectional mixed methods design. METHODS: Three groups
      were included: termination of pregnancy (n = 19), antenatal (n = 9) and never
      pregnant (n = 23). Participants were 13-18 years old. The termination of
      pregnancy and antenatal groups were interviewed, and the never pregnant group
      completed postal questionnaires. RESULTS: Groups differed in individual aspects
      of future orientation, that is, education, career and family, and reasons for
      pregnancy resolution choice. The termination group had more clearly developed and
      longer-term plans for the future with a focus on career. The never pregnant group
      shared aspects of their future orientation with both the antenatal and
      termination of pregnancy groups. The impact of negative discourses about teenage
      pregnancy from others was identified as a significant issue. CONCLUSIONS: How
      pregnant teenage girls view the future has a relationship with their decision to
      terminate or continue with their pregnancy. RELEVANCE TO CLINICAL PRACTICE: The
      findings suggest that working with teenage girls to clarify their views of the
      future may be useful both in preventing future unwanted pregnancy and in
      supporting teenagers in making pregnancy decisions. Supporting pregnant teenagers
      in distancing themselves from negative stereotypes of teenage mothers may also be
      beneficial.

PMID- 24329711
TI  - Imaging techniques for the study of chemical reaction dynamics.

PMID- 24329712
TI  - A snapshot of asparaginase-induced liver insufficiency.

PMID- 24329713
TI  - Attitudes toward interprofessional health care teams scale: a confirmatory factor
      analysis.
AB  - The purpose of this study was to assess reliability and validity of the adapted
      "Attitudes Toward Health Care Teams Scale (ATHCTS)" with graduate professional
      students. Data using a cross-sectional design were collected from 288 graduate
      students who were enrolled at an urban professional university in the Mid
      Atlantic region of the United States. A confirmatory factor analysis (CFA) was
      run and it was found that a two-factor ATHCTS better represented the sample.
      Further, it provided evidence that the two-factor model is valid, and the quality
      of care and time constraint subscales are reliable. This study suggested that the
      two-factor model should be tested with different populations, such as
      undergraduate students, health care professionals and persons at other training
      programs. The ATHCTS can be used as an assessment tool to evaluate the
      effectiveness of educational or training programs designed to improve the
      attitude of graduate students toward interprofessional teamwork.

PMID- 24329714
TI  - Patient-centered care: clarification of its specific elements to facilitate
      interprofessional care.
AB  - Patient-centered care (PCC) has been described as a vague concept, which yields
      an inconsistent operationalization and implementation of this approach to care.
      This integrative review of the literature, guided by the conceptualization of PCC
      as a complex intervention, aimed to identify the specific elements of PCC.
      Conceptual, empirical and clinical literature in different health professions (n
      = 178 articles) was critically analyzed. Comparing and contrasting the
      definitions and descriptions of PCC revealed three specific elements that were
      represented in these components: holistic, collaborative and responsive care.
      Activities that constitute each component were specified. The implementation of
      PCC components is facilitated by a non-specific element: the therapeutic
      relationship. The results inform the development of protocols that can be used to
      promote the fidelity with which PCC is delivered by different professionals in a
      variety of healthcare settings.

PMID- 24329715
TI  - Intercellular trafficking of transcription factors in the vascular tissue
      patterning.
AB  - Throughout life cycles, plants grow in an indeterminate manner by adding new
      cells and organs with specialized functions. Newly emerging cells acquire their
      identities depending on their positions relative to the neighboring cells.
      Exchanging positional signals between cells is critical in this process. Recent
      studies showed that many transcription factors move between cells or between
      organs in forms of proteins and messenger RNA (mRNA). Some of these were found to
      be important positional signals for cell type patterning. Cell type patterning in
      the vascular system is no exception from this. In this review, we describe recent
      discoveries of mobile transcription factors that function as positional signals
      for vascular tissue patterning and propose how these transcription factors
      integrate with other forms of signals. 

PMID- 24329716
TI  - The role of ephrins' receptors and ephrins' ligands in normal placental
      development and disease.
AB  - INTRODUCTION: Ephrin (Eph) receptors and their membrane-anchored ligands, the
      ephrins, participate in a wide spectrum of pathophysiological processes,
      regulating cellular adhesion, migration or chemo-repulsion and tissue/cell
      boundary formation. Recent evidence has further extended the role of Eph
      receptors and their ligands as critical regulators of vascular remodelling during
      embryogenesis. The role of Ephs/ephrins signalling in the angiogenic development
      of murine placentas and in the invasion of the maternal tissues and the
      development of the placental vasculature in humans has currently attracted
      considerable interest. AREAS COVERED: A literature review summarising the most
      recent data in terms of the role of Ephs/ephrins in normal placental development
      and disease, highlighting on their expression status in the different cellular
      populations of the placental vascularity. EXPERT OPINION: Despite the fact that
      the role of Eph/ephrins signalling in normal placental development is still
      unclear, some studies tried to investigate their potential implication in
      placental pathologies, such as preeclampsia and placenta accreta. Even though no
      evidence for their direct implication occurred, their role is an interesting
      field for future research.

PMID- 24329717
TI  - Burden of copy number variation in common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) has been associated recently with a
      dramatic increase in total copy number variation burden, the cause of which is
      unclear. In order to explore further the origin and clinical relevance of this
      finding, we quantified the total genomic copy number variation (CNV) burden in
      affected patients and evaluated clinical details in relationship to total CNV
      burden. No correlation was found between total CNV burden and either patient age
      or time elapsed since symptom onset, and higher total burden did not correlate
      with incidence of malignancy or other subphenotypes. These findings suggest that
      the increased CNV burden is static and intrinsic to CVID as a disease. 

PMID- 24329718
TI  - Overexpression of FOXC1 correlates with poor prognosis in gastric cancer
      patients.
AB  - AIMS: The aim of this study was to determine FOXC1 expression in gastric tissues,
      and the clinical significance of FOXC1 in the development, progression and
      metastasis of gastric cancer (GC). METHODS AND RESULTS: We screened GCs for the
      expression of FOXC1 using the Affymetrix U133 plus 2.0 Gene Chip Array, and found
      that expression was significantly higher in GC tissues than in controls.
      Furthermore, we validated the expression levels of FOXC1 using real-time
      quantitative RT-PCR (qRT-PCR), and of FOXC1 using immunohistochemistry (IHC). Our
      study showed that expression levels of FOXC1 mRNA and FOXC1 in GC tissues were
      significantly higher than those in corresponding non-tumour tissues. High FOXC1
      expression correlated with the degree of histological differentiation (P < 0.01),
      TNM stage (P < 0.001), invasive depth (P < 0.05), lymph node metastasis (P <
      0.05), and distant metastasis (P < 0.01). Survival analysis revealed that
      patients with high FOXC1 expression had shorter overall survival than those with
      low expression (P < 0.001). Multivariate analysis showed that high FOXC1
      expression was an independent prognostic factor for GC patients (P < 0.01).
      CONCLUSIONS: Overexpression of FOXC1 may play a key role in the progression of
      GC, and FOXC1 expression may serve as a useful marker for predicting the outcome
      of patients with GC.

PMID- 24329719
TI  - Effect of different head-neck positions on physical and psychological stress
      parameters in the ridden horse.
AB  - Different head-neck positions (HNPs) are used in equestrian sports and are
      regarded as desirable for training and competition by riders, judges and
      trainers. Even though some studies have been indicative of hyperflexion having
      negative effects on horses, this unnatural position is frequently used. In the
      present study, the influence of different HNPs on physical and psychological
      stress parameters in the ridden horse was investigated. Heart rate (HR), heart
      rate variability (HRV) and blood cortisol levels were measured in 18 horses. Low
      frequency (LF) and high frequency (HF) are power components in the frequency
      domain measurement of HRV which show the activity of the sympathetic and
      parasympathetic nervous system. Values were recorded at rest, while riding with a
      working HNP and while riding with hyperflexion of the horse's head, neck and
      poll. In addition, rideability and behaviour during the different investigation
      stages were evaluated by the rider and by an observer. Neither the HR nor the HRV
      showed a significant difference between working HNP (HR = 105 +/- 22/min; LF/HF =
      3.89 +/- 5.68; LF = 37.28 +/- 10.77%) and hyperflexion (HR = 110 +/- 18; LF/HF =
      1.94 +/- 2.21; LF = 38.39 +/- 13.01%). Blood cortisol levels revealed a
      significant increase comparing working HNP (158 +/- 60 nm) and hyperflexion (176
      +/- 64 nm, p = 0.01). The evaluation of rider and observer resulted in clear
      changes of rideability and behavioural changes for the worse in all parameters
      collected between a working HNP and hyperflexion. In conclusion, changes of the
      cortisol blood level as a physical parameter led to the assumption that
      hyperflexion of head, neck and poll effects a stress reaction in the horse, and
      observation of the behaviour illustrates adverse effects on the well-being of
      horses during hyperflexion. 

PMID- 24329720
TI  - The medical-legal responsibilities of a dialysis unit medical director.
AB  - The specialty of Nephrology, by virtue of its relationship with the dialysis
      procedure, is highly vulnerable to litigation. As is the case with all
      nephrologists, a dialysis unit medical director is not immune to medical
      malpractice suits, and can be held liable for any act of perceived or potential
      harm to any dialysis patient, regardless of the director's level of involvement.
      The medical director, per the Centers for Medicare and Medicaid Services (CMS)
      Conditions of Participation, accepts the responsibilities, accountability, and
      consequent legal liabilities of the quality of the medical care provided to every
      dialysis patient in the unit. This review is a synopsis of lawsuits filed against
      medical directors of dialysis units in the past forty years. Six categories of
      legal actions were noted; medical malpractice, fraudulent claims, self-referral
      and Stark Law, discrimination, negligence, and violation of patient autonomy and
      dignity. 

PMID- 24329721
TI  - Stability of key micronutrients added to fortified maize flours and corn meal.
AB  - Maize is a dietary staple in many countries. Although nutritious in many ways and
      a good source of energy, typical maize lacks several key micronutrients (MNs)
      that are often added to maize meals or flours to enhance nutritional value. Many
      factors affect MN stability in maize products, including uncontrolled conditions
      during distribution, long storage times, and MN premix composition. Consumer
      preparation also affects the final MN content of food. This review summarizes
      research relating to MN stability during processing, transport, storage, and meal
      preparation, focusing on those MNs most often added to maize and maize-based
      foods. Significant losses in B vitamins (B1, B2, B3, B6, B9, and B12) occur
      during manufacturing, distribution, and cooking. Added minerals (e.g., iron,
      zinc, calcium) are generally retained, although phytates in corn may affect
      bioavailability. Vitamins A and D3 are recent additions to fortification premixes
      for maize and are not well studied. Although there have been numerous studies of
      MN fortification in wheat flour, maize has not been as thoroughly examined, so
      recommendations are not as well supported. Future investigations should include
      well-designed and executed studies of the most labile MNs added to maize flours
      and meals, and their fate during all steps of processing, shipping, and
      preparation. 

PMID- 24329722
TI  - Heterozygosity and orange coloration are associated in the guppy (Poecilia
      reticulata).
AB  - The good-genes-as-heterozygosity hypothesis predicts that more elaborate male
      sexual ornaments are associated with higher levels of heterozygosity. Recent
      theoretical work suggests that such associations are likely to arise in finite,
      structured populations. We investigated the correlation between multilocus
      heterozygosity (MLH), which was estimated using 13 microsatellite loci, and male
      coloration in a wild population of guppies (Poecilia reticulata), a model species
      in sexual selection research. We found that MLH was a significant predictor of
      the relative area of orange spots, a trait that is subject to strong female
      preference in this species. Neither the relative area of black spots nor the
      number of black or orange spots was significantly correlated with MLH. We found
      no statistical support for local effects (i.e. strong effects of heterozygosity
      at specific markers), which suggests that relative orange spots area reflects
      genome-wide heterozygosity. 

PMID- 24329723
TI  - Epileptic seizures as condensed sleep: an analysis of network dynamics from
      electroencephalogram signals.
AB  - Both deepening sleep and evolving epileptic seizures are associated with
      increasing slow-wave activity. Larger-scale functional networks derived from
      electroencephalogram indicate that in both transitions dramatic changes of
      communication between brain areas occur. During seizures these changes seem to be
      'condensed', because they evolve more rapidly than during deepening sleep. Here
      we set out to assess quantitatively functional network dynamics derived from
      electroencephalogram signals during seizures and normal sleep. Functional
      networks were derived from electroencephalogram signals from wakefulness, light
      and deep sleep of 12 volunteers, and from pre-seizure, seizure and post-seizure
      time periods of 10 patients suffering from focal onset pharmaco-resistant
      epilepsy. Nodes of the functional network represented electrical signals recorded
      by single electrodes and were linked if there was non-random cross-correlation
      between the two corresponding electroencephalogram signals. Network dynamics were
      then characterized by the evolution of global efficiency, which measures ease of
      information transmission. Global efficiency was compared with relative delta
      power. Global efficiency significantly decreased both between light and deep
      sleep, and between pre-seizure, seizure and post-seizure time periods. The
      decrease of global efficiency was due to a loss of functional links. While global
      efficiency decreased significantly, relative delta power increased except between
      the time periods wakefulness and light sleep, and pre-seizure and seizure. Our
      results demonstrate that both epileptic seizures and deepening sleep are
      characterized by dramatic fragmentation of larger-scale functional networks, and
      further support the similarities between sleep and seizures. 

PMID- 24329725
TI  - UK owner preferences for treatment of feline injection site sarcomas.
AB  - OBJECTIVES: Feline injection site sarcomas are therapeutically challenging
      because of their locally invasive nature. Several protocols recommend that the
      two perceived high-risk adjuvanted vaccines should be administered into distinct
      anatomical sites ("left hind leg leukaemia, right hind leg rabies"), which should
      aid surgical resection. This has resulted in a change in tumour distribution with
      an increased proportion situated caudal to the diaphragm when such a policy is
      adopted. The aim of this study was to determine UK cat owners' attitudes towards
      surgical treatments of different anatomical regions. METHODS: A cross-sectional
      study of an anonymous convenience sample of UK cat owners was conducted from
      September to December, 2012 using an internet-based survey. RESULTS: There were a
      total of 208 respondents: 39% would pursue surgery regardless of tumour site. One
      percent would not pursue surgery. Of the remainder, respondents would not allow
      amputation of the forelimb (20%), hindlimb (15%) or tail (15%). Twenty-six, 32
      and 27% would not have surgical treatment of the inter-scapular region, chest or
      abdomen, respectively. The majority of respondents were willing to travel up to
      100 miles for radiotherapy or chemotherapy (66 and 69%, respectively). CLINICAL
      SIGNIFICANCE: The current feline vaccine site recommendations may not be
      appropriate for UK cat owners.

PMID- 24329726
TI  - Plasticity of functional traits varies clinally along a rainfall gradient in
      Eucalyptus tricarpa.
AB  - Widespread species often occur across a range of climatic conditions, through a
      combination of local genetic adaptations and phenotypic plasticity. Species with
      greater phenotypic plasticity are likely to be better positioned to cope with
      rapid anthropogenic climate changes, while those displaying strong local
      adaptations might benefit from translocations to assist the movement of adaptive
      genes as the climate changes. Eucalyptus tricarpa occurs across a climatic
      gradient in south-eastern Australia, a region of increasing aridity, and we
      hypothesized that this species would display local adaptation to climate. We
      measured morphological and physiological traits reflecting climate responses in
      nine provenances from sites of 460 to 1040 mm annual rainfall, in their natural
      habitat and in common gardens near each end of the gradient. Local adaptation was
      evident in functional traits and differential growth rates in the common gardens.
      Some traits displayed complex combinations of plasticity and genetic divergence
      among provenances, including clinal variation in plasticity itself. Provenances
      from drier locations were more plastic in leaf thickness, whereas leaf size was
      more plastic in provenances from higher rainfall locations. Leaf density and
      stomatal physiology (as indicated by delta(13)C and delta(18)O) were highly and
      uniformly plastic. In addition to variation in mean trait values, genetic
      variation in trait plasticity may play a role in climate adaptation.

PMID- 24329727
TI  - Standardized endoscopic reporting.
AB  - The need for standardized language is increasingly obvious, also within
      gastrointestinal endoscopy. A systematic approach to the description of
      endoscopic findings is vital for the development of a universal language, but
      systematic also means structured, and structure is inherently a challenge when
      presented as an alternative to the normal spoken word. The efforts leading to the
      "Minimal Standard Terminology" (MST) of gastrointestinal endoscopy offer a
      standardized model for description of endoscopic findings. With a combination of
      lesion descriptors and descriptor attributes, this system gives guidance to
      appropriate descriptions of lesions and also has a normative effect on
      endoscopists in training. The endoscopic report includes a number of items not
      related to findings per se, but to other aspects of the procedure, formal,
      technical, and medical. While the MST sought to formulate minimal lists for some
      of these aspects (e.g. indications), they are not all well suited for the
      inherent structure of the MST, and many are missing. Thus, the present paper
      offers a recommended standardization also of the administrative, technical, and
      other "peri-endoscopic" elements of the endoscopic report; important also are the
      numerous quality assurance initiatives presently emerging. Finally, the image
      documentation of endoscopic findings is becoming more obvious-and accessible.
      Thus, recommendations for normal procedures as well as for focal and diffuse
      pathology are presented. The recommendations are "minimal," meaning that
      expansions and subcategories will likely be needed in most centers. Still, with a
      stronger common grounds, communication within endoscopy will still benefit. 

PMID- 24329728
TI  - The novel SLCO2A1 heterozygous missense mutation p.E427K and nonsense mutation
      p.R603* in a female patient with pachydermoperiostosis with an atypical
      phenotype.

PMID- 24329729
TI  - Juvenile idiopathic arthritis-associated uveitis at an Italian tertiary referral
      center: clinical features and complications.
AB  - PURPOSE: To describe the frequencies and risk factors of ocular complications and
      poor visual outcomes in children with juvenile idiopathic arthritis (JIA).
      METHODS: Retrospective cohort study, including 69 consecutive children (116 eyes)
      affected by JIA-associated uveitis managed at a tertiary uveitis clinic. RESULTS:
      The incidence of visual loss to the 20/50 or worse threshold was 0.04/eye-year
      (EY) and to the 20/200 or worse threshold was 0.02/EY. The most common
      complications at baseline were posterior synechiae (52%), band keratopathy (38%),
      and cataract (12%). Risk factor for a visual acuity threshold of 20/50 or worse
      included hypotony (p = 0.01; hazard ratio [HR] 3.7; 95% CI 1.3-10.4); anterior
      chamber flare >1 (p = 0.04; HR 1.3; 95% CI 0.5-3.4); a positive antinuclear
      antibody (ANA) (p = 0.02; HR1.4; 95% CI 0.8-2.4). Hypotony and positive ANA are
      also associated to the 20/200 or worse threshold (p = 0.03; HR 5.1; 95% CI 1.1
      23.9 and p = 0.04; HR 1.0; 95% CI 0.4-2.3; respectively). Use of
      immunosuppressive drugs was associated with a reduced risk of visual loss of
      20/200 or worse (odds ratio 0.14, 95% CI, 0.02-1.29; p = 0.04). CONCLUSIONS: Loss
      of vision and ocular complications still occur among children with JIA-related
      uveitis. Prompt diagnosis and a strict follow up associated to immunosuppressive
      therapy may decrease the poor visual outcome.

PMID- 24329731
TI  - Newly paired zebra finches have higher dopamine levels and immediate early gene
      Fos expression in dopaminergic neurons.
AB  - Most birds are socially monogamous, yet little is known about the neural pathways
      underlying avian monogamy. Recent studies have implicated dopamine as playing a
      role in courtship and affiliation in a socially monogamous songbird, the zebra
      finch (Taeniopygia guttata). In the present study, we sought to understand the
      specific contribution to pair formation in zebra finches of the mesolimbic
      dopaminergic pathway that projects from the midbrain ventral tegmental area to
      the nucleus accumbens. We observed that paired birds had higher levels of
      dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ventral medial
      striatum, where the nucleus accumbens is situated, than unpaired birds.
      Additionally, we found that the percentage of dopaminergic neurons expressing
      immediate early gene Fos, a marker of neuronal activity, was higher in the
      ventral tegmental area of paired birds than in that of unpaired birds. These data
      are consistent with a role for the mesolimbic dopaminergic pathway in pair
      formation in zebra finches, suggesting the possibility of a conserved neural
      mechanism of monogamy in birds and mammals. 

PMID- 24329730
TI  - Rapid and persistent impairments of the forelimb motor representations following
      cervical deafferentation in rats.
AB  - Skilled motor control is regulated by the convergence of somatic sensory and
      motor signals in brain and spinal motor circuits. Cervical deafferentation is
      known to diminish forelimb somatic sensory representations rapidly and to impair
      forelimb movements. Our focus was to determine what effect deafferentation has on
      the motor representations in motor cortex, knowledge of which could provide new
      insights into the locus of impairment following somatic sensory loss, such as
      after spinal cord injury or stroke. We hypothesized that somatic sensory
      information is important for cortical motor map topography. To investigate this
      we unilaterally transected the dorsal rootlets in adult rats from C4 to C8 and
      mapped the forelimb motor representations using intracortical microstimulation,
      immediately after rhizotomy and following a 2-week recovery period. Immediately
      after deafferentation we found that the size of the distal representation was
      reduced. However, despite this loss of input there were no changes in motor
      threshold. Two weeks after deafferentation, animals showed a further distal
      representation reduction, an expansion of the elbow representation, and a small
      elevation in distal movement threshold. These changes were specific to the
      forelimb map in the hemisphere contralateral to deafferentation; there were no
      changes in the hindlimb or intact-side forelimb representations. Degradation of
      the contralateral distal forelimb representation probably contributes to the
      motor control deficits after deafferentation. We propose that somatic sensory
      inputs are essential for the maintenance of the forelimb motor map in motor
      cortex and should be considered when rehabilitating patients with peripheral or
      spinal cord injuries or after stroke. 

PMID- 24329732
TI  - ESCMID guidelines for the management of the infection control measures to reduce
      transmission of multidrug-resistant Gram-negative bacteria in hospitalized
      patients.
AB  - Healthcare-associated infections due to multidrug-resistant Gram-negative
      bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide.
      These evidence-based guidelines have been produced after a systematic review of
      published studies on infection prevention and control interventions aimed at
      reducing the transmission of MDR-GNB. The recommendations are stratified by type
      of infection prevention and control intervention and species of MDR-GNB and are
      presented in the form of 'basic' practices, recommended for all acute care
      facilities, and 'additional special approaches' to be considered when there is
      still clinical and/or epidemiological and/or molecular evidence of ongoing
      transmission, despite the application of the basic measures. The level of
      evidence for and strength of each recommendation, were defined according to the
      GRADE approach. 

PMID- 24329733
TI  - Reverse algorithm for syphilis screening more than halved false positive test
      results in Brazilian blood donors.

PMID- 24329734
TI  - Comparison of magnetic resonance imaging with standing cervical radiographs for
      evaluation of vertebral canal stenosis in equine cervical stenotic myelopathy.
AB  - REASONS FOR PERFORMING STUDY: The sensitivity and specificity of lateral cervical
      radiographs to evaluate horses suspected of cervical stenotic myelopathy (CSM)
      are limited by the assessment being restricted to the sagittal plane. OBJECTIVE:
      To determine whether magnetic resonance imaging (MRI) allows for a more accurate
      identification of stenosis than lateral cervical radiographs in horses with CSM.
      STUDY DESIGN: Case control study. METHODS: Nineteen Thoroughbred horses with CSM
      (17 males, 2 females, age 6-50 months) were compared to 9 control Thoroughbreds
      (6 males, 3 females, age 9-67 months). Ante mortem, the subjects had neurological
      examinations and standing cervical radiographs with sagittal ratios calculated
      from C3 to C7. Intact cervical column MRI scans and histological examinations of
      the spinal cord were performed post mortem. Morphometric parameters were measured
      on the vertebral canal, spinal cord and intervertebral foramen. RESULTS:
      Radiographic cervical canal height measurements categorised by standard minimal
      sagittal diameter intravertebral and intervertebral ratios produced several false
      positive and false negative determinations of canal stenosis as defined by spinal
      cord histopathology. Post mortem MRI measurements of canal area and cord canal
      area ratio more accurately predicted sites of cord compression in CSM cases. No
      differences in spinal cord measurements were observed when comparing CSM to
      control horses, but each of the vertebral canal parameters achieved significance
      at multiple sites. CONCLUSIONS: Vertebral canal area and cord canal area ratio
      are better parameters to predict the location of cervical canal stenosis compared
      to only the sagittal plane of canal height. Additional visual planes and
      measurements obtained by MRI, specifically vertebral canal area and the cord
      canal area ratio, will provide a more accurate method to identify regions of
      canal stenosis than lateral cervical radiographs. The development of MRI or
      computed tomography equipment capable of evaluating the cervical column of mature
      horses may substantially enhance evaluation of CSM patients. The Summary is
      available in Chinese - see Supporting information.

PMID- 24329735
TI  - Cost effectiveness analysis of a next generation risk assessment score for
      cardiovascular disease.
AB  - OBJECTIVES: The goal of this study is to determine the cost-effectiveness of
      MIRISK VP, a next generation coronary heart disease risk assessment score, in
      correctly reclassifying and appropriately treating asymptomatic, intermediate
      risk patients. STUDY DESIGN: A Markov model was employed with simulated subjects
      based on the Multi-Ethnic Study of Atherosclerosis (MESA). This study evaluated
      three treatment strategies: (i) practice at MESA enrollment, (ii) current
      guidelines, and (iii) MIRISK VP in MESA. METHODS: The model assessed patient
      healthcare costs and outcomes, expressed in terms of life years and quality
      adjusted life years (QALYs), over the lifetime of the cohort from the provider
      and payer perspective. A total of 50,000 hypothetical individuals were used in
      the model. A sensitivity analysis was conducted (based on the various input
      parameters) for the entire cohort and also for individuals aged 65 and older.
      RESULTS: Guiding treatment with MIRISK VP leads to the highest net monetary
      benefits when compared to the 'Practice at MESA Enrollment' or to the 'Current
      Guidelines' strategies. MIRISK VP resulted in a lower mortality rate from any CHD
      event and a modest increase in QALY of 0.12-0.17 years compared to the other two
      approaches. LIMITATIONS: This study has limitations of not comparing performance
      against strategies other than the FRS, the results are simulated as with all
      models, the model does not incorporate indirect healthcare costs, and the impact
      of patient or physician behaviors on outcomes were not taken into account.
      CONCLUSIONS: MIRISK VP has the potential to improve patient outcomes compared to
      the alternative strategies. It is marginally more costly than both the 'Practice
      at MESA Enrollment' and the 'Current Guidelines' strategies, but it provides
      increased effectiveness, which leads to positive net monetary benefits over
      either strategy.

PMID- 24329736
TI  - Association of soluble receptor for advanced glycation end products levels with
      hypertensive albuminuria.
AB  - OBJECTIVE: Soluble receptor for advanced glycation end products (sRAGE) levels
      have been found to be decreased in chronic inflammatory diseases including
      atherosclerosis, hypertension and renal failure. This study evaluated the
      relationship between sRAGE concentrations and urinary albumin excretion in
      patients with essential hypertension. METHODS: A total of 200 consecutive
      patients with essential hypertension were enrolled and were divided into 3
      groups. RESULTS: Plasma sRAGE levels were significantly lower in hypertensive
      patients with micro- or macroalbuminuria compared with those in hypertensive
      patients with normoalbuminuria, and the values in the macroalbuminuria group were
      even lower than in the microalbuminuria group (128.6+/-24.2, 244.6+/-37.6+/
      313.6+/-30.7 pg/ml, respectively). In addition, plasma sRAGE level was an
      independent determinant of log urinary albumin excretion in patients with
      essential hypertension (beta=-0.267, P<0.05). CONCLUSIONS: sRAGE may play a role
      in the pathogenic processes that link albuminuria, chronic inflammation and
      oxidative stress in hypertensive patients.

PMID- 24329737
TI  - The Role of Vitamin D in Atherosclerosis Inflammation Revisited: More a Bystander
      than a Player?
AB  - Levels of 25-hydroxy vitamin D [25(OH)D] are reported to be decreased in
      cardiovascular disease (CVD) and in other chronic immunopathologies. Vitamin D
      (vitD) has been shown to be significantly linked to mortality, and is thought to
      be a predictor of survival. Therefore, supplementation with vitD has been
      suggested as an option to improve clinical outcomes. In contrast to the causal
      assumption, we hypothesize that the decreased vitD levels, seen in patients with
      CVD and chronic immunopathologies is secondary to inflammation and not as
      pathophysiologically relevant as currently suggested. Under these conditions, low
      vitD might be mainly caused by oxidative stress that results from chronic, immune
      mediated vascular and systemic inflammation seen in patients with CVD. The
      oxidative environment most likely causes biodegradation of vitD and interferes
      with key enzymes, disturbing the biosynthesis of 25(OH)D and 1,25(OH)D. Thus far,
      no clear evidence of a beneficial effect of vitD supplements exists, beyond
      treating vitD deficiency to improve skeletal health. Moreover, a prolonged and/or
      high dose vitD supplementation, unless needed to correct actual vitD deficiency
      [levels of 25(OH)D<20 ng/ml)] may even be immunologically harmful by
      downregulating Th1 immune responses and indirectly upregulating Th2 immune
      activation with potential detrimental metabolic and cardiovascular effects. Large
      randomized controlled studies of vitD with multiple outcomes (skeletal,
      metabolic, cardiovascular and mental) are urgently needed. 

PMID- 24329738
TI  - Microclimate next to the skin: influence on percutaneous absorption of caffeine
      (ex-vivo study).
AB  - BACKGROUND/PURPOSE: Contact between skin surface and external environment induces
      a microclimate at the skin surface. That microclimate affects skin interaction
      with xenobiotics substances. We have developed a new device to explore the
      influence of environmental parameters, on percutaneous absorption. The aim of
      this study was to study the influence of external humidity and temperature on
      percutaneous absorption of caffeine. METHODS: Six exposure conditions were
      tested: four by combining two temperatures (27 degrees C and 42 degrees C) with
      two relative humidities (28% and 70%), performed by our device and two others by
      using Franz diffusion cell (unoccluded conditions, with skin surface in contact
      with ambient laboratory environment (27 degrees C/33%) and in occluded conditions
      with skin surface covering by impermeable membrane). RESULTS: Kinetic curve
      profile of percutaneous absorption of caffeine revealed different shapes
      characteristics depending on environmental exposure conditions. These profiles
      were related to evaporative process, of deposited preparation on skin surface
      combined with water uptake resulting from water flux through skin. CONCLUSION:
      Our results highlight a preponderant role of microclimate above the skin on
      percutaneous absorption of caffeine. The device used in this study will be a
      useful tool to investigate ex vivo, the influence of microclimate on percutaneous
      absorption.

PMID- 24329739
TI  - On narcissistic perversion.

PMID- 24329740
TI  - Examining the causal model linking health literacy to health outcomes of asthma
      patients.
AB  - AIMS AND OBJECTIVES: To explore health literacy status in asthma patients and to
      examine the causal model linking health literacy to health outcome-related
      factors via mediator and moderator variables. BACKGROUND: Understanding how low
      health literacy may influence health outcomes is important. DESIGN: This is a
      cross-sectional survey study. METHODS: A total of 326 asthma patients aged 20
      years and older (average: 51 +/- 18.3 years) were recruited by purposive sampling
      from pulmonary medicine outpatient departments at three medical centres and a
      regional teaching hospital in northern Taiwan. Data were collected via structured
      questionnaires, including measures of socio-demographic and disease
      characteristics; medical decision-making; asthma knowledge, attitudes and self
      efficacy; healthcare experience and health outcome-related factors (metered-dose
      inhaler/dry-powder inhaler usage proficiency, medical use, self-management
      behaviour). Three hundred patients who met the inclusion criteria and completed
      the questionnaire survey were analysed. RESULTS: Overall, 217 subjects (72.3%)
      had adequate functional health literacy, 42 (14%) had inadequate functional
      health literacy, and 41 (13.7%) had marginal functional health literacy.
      Subjects' average asthma knowledge, attitudes and self-efficacy scores were 7.23
      +/- 2.69, 51.46 +/- 6.18 and 58.31 +/- 8.10, respectively. Health literacy
      correlated positively with asthma knowledge (r = 0.605), attitudes (r = 0.192)
      and medical decision-making (r = 0.413). CONCLUSIONS: Health literacy is
      positively associated with proficiency in metered-dose inhaler usage, asthma
      knowledge, attitudes and medical decision-making, but is not significantly
      associated with medical care use and self-management behaviour. Health literacy
      had an indirect effect on self-management behaviour through the mediation effect
      of asthma attitudes. No moderator was found for the effect of health literacy on
      health outcome-related factors. RELEVANCE TO CLINICAL PRACTICE: Results of this
      study may help to develop adequate intervention strategies to improve the health
      outcomes of asthma patients.

PMID- 24329741
TI  - The labelling of all medicinal products as Dependent on Animal Research would be
      a minefield to be avoided at all costs.

PMID- 24329742
TI  - An analysis of the use of dogs in predicting human toxicology and drug safety.
AB  - Dogs remain the main non-rodent species in preclinical drug development. Despite
      the current dearth of new drug approvals and meagre pipelines, this continues,
      with little supportive evidence of its value or necessity. To estimate the
      evidential weight provided by canine data to the probability that a new drug may
      be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive
      dataset of 2,366 drugs with both animal and human data, including tissue-level
      effects and Medical Dictionary for Regulatory Activities (MedDRA) Level 1-4
      biomedical observations. The resulting LRs show that the absence of toxicity in
      dogs provides virtually no evidence that adverse drug reactions (ADRs) will also
      be absent in humans. While the LRs suggest that the presence of toxic effects in
      dogs can provide considerable evidential weight for a risk of potential ADRs in
      humans, this is highly inconsistent, varying by over two orders of magnitude for
      different classes of compounds and their effects. Our results therefore have
      important implications for the value of the dog in predicting human toxicity, and
      suggest that alternative methods are urgently required. 

PMID- 24329743
TI  - Current status of animal welfare and animal rights in China.
AB  - In the past few years, new social passions have sparked on the Chinese mainland.
      At the centre of these burgeoning passions is a focus on animal welfare, animal
      treatment, and even animal rights, by the public and academic sectors. With
      China's rapid economic changes and greater access to information from around the
      world, societal awareness of animal issues is rising very fast. Hastening this
      paradigm shift were several highly public incidents involving animal cruelty,
      including exposes on bear bile harvesting for traditional Chinese medicine, the
      thousands of dogs rescued from China's meat trade, and the call to boycott shark
      fin soup and bird nest soup. This article outlines the current status of
      campaigning by animal advocates in China (specifically the animal rights
      movement) from three interlinked perspectives: wildlife conservation, companion
      animal protection, and laboratory animal protection. By reviewing this
      campaigning, we attempt to present not only the political and social impact of
      the concept of animal rights, but also the perceptions of, and challenges to,
      animal rights activities in China. 

PMID- 24329744
TI  - A phantom pig abdomen as an alternative for testing robotic surgical systems: our
      experience.
AB  - The use of animals for testing and validating new medical devices and surgical
      techniques has raised ethical issues for a long time. Following the introduction
      of the Three Rs principle, significant efforts have been made to achieve a
      reduction in the numbers of animals used in testing. Nevertheless, the number of
      large animals used for testing purposes is still too high. This article describes
      a potential alternative to the use of large animals in the early phase of the
      development of surgical equipment -- a high-definition phantom pig abdomen. The
      phantom pig abdomen was developed from computed tomography scans by using
      affordable materials, and it was used with two different robotic platforms. It
      permitted the testing of minimally-invasive robotic pancreatic enucleation, with
      or without intraoperative ultrasound guidance. The phantom pig abdomen has proven
      to be a realistic tool, with the potential to reduce the cost and time-frame of
      the experiments.

PMID- 24329745
TI  - Validation of the hepatocyte-like HPCT-1E3 cell line as an in vitro model for the
      prediction of acute in vivo toxicity.
AB  - In a pilot study, we tested 20 randomly-selected chemicals for their cytotoxicity
      toward the HPCT-1E3 cell model, in order to prove the ability of this in vitro
      model to predict human acute in vivo toxicity. The study revealed that, in
      contrast to most other in vitro models, results from the HPCT-1E3 cell-based
      system show better correlation with the more-relevant human acute lethal doses,
      whereas results from most other systems have a high predictivity for human lethal
      serum concentrations. For the prevalidation of the HPCT-1E3 model as a surrogate
      for regulatory acute in vivo toxicity tests, we have now expanded the list of
      tested chemicals to 57 substances, and have compared the results with data from
      the HepG2 cell assay. Again, a better correlation of HPCT-1E3 IC50 values with
      human oral lethal doses, as compared to correlation with human lethal serum
      concentrations, was observed after the pooling of all the tested substances (r(2)
      = 0.53 [P < 0.001] and r(2) = 0.41 [P = 0.009], respectively). Therefore, the
      HPCT-1E3 in vitro model may be a valuable tool for prediction of human oral
      toxicity, and may help to further reduce the number of animals used for in vivo
      toxicity tests. 

PMID- 24329746
TI  - A critical review of anaesthetised animal models and alternatives for military
      research, testing and training, with a focus on blast damage, haemorrhage and
      resuscitation.
AB  - Military research, testing, and surgical and resuscitation training, are aimed at
      mitigating the consequences of warfare and terrorism to armed forces and
      civilians. Traumatisation and tissue damage due to explosions, and acute loss of
      blood due to haemorrhage, remain crucial, potentially preventable, causes of
      battlefield casualties and mortalities. There is also the additional threat from
      inhalation of chemical and aerosolised biological weapons. The use of
      anaesthetised animal models, and their respective replacement alternatives, for
      military purposes -- particularly for blast injury, haemorrhaging and
      resuscitation training -- is critically reviewed. Scientific problems with the
      animal models include the use of crude, uncontrolled and non-standardised methods
      for traumatisation, an inability to model all key trauma mechanisms, and complex
      modulating effects of general anaesthesia on target organ physiology. Such
      effects depend on the anaesthetic and influence the cardiovascular system,
      respiration, breathing, cerebral haemodynamics, neuroprotection, and the
      integrity of the blood-brain barrier. Some anaesthetics also bind to the NMDA
      brain receptor with possible differential consequences in control and
      anaesthetised animals. There is also some evidence for gender-specific effects.
      Despite the fact that these issues are widely known, there is little published
      information on their potential, at best, to complicate data interpretation and,
      at worst, to invalidate animal models. There is also a paucity of detail on the
      anaesthesiology used in studies, and this can hinder correct data evaluation.
      Welfare issues relate mainly to the possibility of acute pain as a side-effect of
      traumatisation in recovered animals. Moreover, there is the increased potential
      for animals to suffer when anaesthesia is temporary, and the procedures invasive.
      These dilemmas can be addressed, however, as a diverse range of replacement
      approaches exist, including computer and mathematical dynamic modelling of the
      human body, cadavers, interactive human patient simulators for training, in vitro
      techniques involving organotypic cultures of target organs, and epidemiological
      and clinical studies. While the first four of these have long proven useful for
      developing protective measures and predicting the consequences of trauma, and
      although many phenomena and their sequelae arising from different forms of trauma
      in vivo can be induced and reproduced in vitro, non-animal approaches require
      further development, and their validation and use need to be coordinated and
      harmonised. Recommendations to these ends are proposed, and the scientific and
      welfare problems associated with animal models are addressed, with the future
      focus being on the use of batteries of complementary replacement methods deployed
      in integrated strategies, and on greater transparency and scientific cooperation.

PMID- 24329747
TI  - The Three Rs - do we need a new principle?

PMID- 24329748
TI  - Implementing the in vitro pyrogen test: one more step toward replacing animal
      experimentation.

PMID- 24329749
TI  - The need to improve experimental design.

PMID- 24329750
TI  - A toolbox for animal welfare education.

PMID- 24329751
TI  - 7. The factors governing progress.

PMID- 24329752
TI  - Vernalization, gibberellic acid and photo period are important signals of yield
      formation in timothy (Phleum pratense).
AB  - Timothy (Phleum pratense) is a widely grown perennial forage grass in the Nordic
      region. The canopy consists of three tiller types, of which the stem forming
      vegetative elongating (ELONG) tiller and generative (GEN) tillers contribute the
      most to dry matter yield. In this study, the regulation of tiller formation by
      vernalization, day length (DL) [12 h, short day length (SD); 16 h, long day
      length (LD)] and gibberellic acid (GA) was investigated in two timothy cultivars.
      Vernalization resulted in a shift of ELONG to GEN tillers. No vernalization was
      required for the development of ELONG tillers but SD strictly arrested stem
      elongation. Vernalization is an important regulator of tiller development but it
      seemed to be upstream regulated by DL. LD was essential for floral transition and
      could not be substituted by GA and/or vernalization treatments. Genotypic
      variation was found in the development of GEN tillers. The ability to produce GEN
      tillers was associated with significant upregulation of PpVRN3. PpVRN1 expression
      peaked at the time of vegetative/generative transition, and PpVRN3 after the
      transfer to LD, suggesting them to have similar functions with cereal
      vernalization genes. PpVRN1 alone was not sufficient to activate flowering, and
      upregulation of PpVRN3 possibly together with PpPpd1 was required. Although
      vernalization downregulated PpMADS10, this gene did not act as a clear flowering
      repressor. Our results show that flowering signals alter the tiller composition,
      so they have important effects on yield formation of timothy. 

PMID- 24329753
TI  - Consistent absence of HER2 expression, regardless of HER2 amplification status,
      in neuroendocrine carcinomas of the stomach.
AB  - AIMS: To determine HER2 amplification status and HER2 overexpression status in
      neuroendocrine carcinomas (NECs) of the stomach. METHODS AND RESULTS: We analysed
      51 gastric NECs, including 15 pure NECs and 36 NECs associated with
      adenocarcinoma and/or dysplasia, for HER2 amplification by dual-colour
      chromogenic in-situ hybridization, and for HER2 expression by
      immunohistochemistry. HER2 amplification was observed in three NECs (6%) and in
      seven (19%) cases of adenocarcinoma/dysplasia associated with NEC.
      Immunohistochemically, all of the NECs, including those showing HER2
      amplification, lacked HER2 expression. On the other hand, positive and equivocal
      HER2 overexpression was observed in three (8%) and six (17%) cases of
      adenocarcinoma/dysplasia associated with NEC, respectively. CONCLUSIONS: HER2
      expression is consistently absent in gastric NECs, regardless of HER2
      amplification status or association with HER2-positive adenocarcinoma/dysplasia
      components. Accordingly, HER2 is unlikely to be a valid therapeutic target in
      gastric NECs. Also, the absence of HER2 expression in NECs could be one of the
      causes of intratumoral heterogeneity of HER2 expression in gastric cancers.

PMID- 24329754
TI  - Enzymatic activity profile of a Brazilian culture collection of Candida albicans
      isolated from diabetics and non-diabetics with oral candidiasis.
AB  - The secretion of hydrolytic enzymes is a fundamental virulence factor of Candida
      albicans to develop disease. The objective of this study was to characterise the
      virulence of 148 clinical isolates of C. albicans from oral candidiasis by
      assessing the expression of phospholipase (PL) and secreted aspartyl proteinase
      (SAP). Isolates were obtained from healthy subjects (HS) and diabetics (DOC) and
      non-diabetics with oral candidiasis (NDOC). An aliquot (5 MUl) of each cell
      suspension was inoculated on PL and SAP agar plates and incubated. Enzymes
      secretion was detected by the formation of an opaque halo around the colonies and
      enzymatic activity (PZ) was determined by the ratio between colony diameter and
      colony diameter plus the halo zone. Statistical comparisons were made by a one
      way anova followed by Tukey's post hoc test (alpha = 0.05). The clinical sources
      of C. albicans had significant effect (P < 0.001) on the PZ values of both
      enzymes. For PL, clinical isolates from NDOC and DOC had highest enzymatic
      activity than those from HS (P < 0.05), with no significant differences between
      them (P = 0.506). For SAP, C. albicans from NDOC showed the lower enzymatic
      activity (P < 0.001). There were no significant differences between isolates from
      HS and DOC (P = 0.7051). C. albicans isolates from NDOC and DOC patients showed
      an increased production of PL. 

PMID- 24329755
TI  - The evolution of resistance against good and bad infections.
AB  - Opportunities for genetic exchange are abundant between bacteria and foreign
      genetic elements (FGEs) such as conjugative plasmids, transposable elements and
      bacteriophages. The genetic novelty that may arise from these forms of genetic
      exchange is potentially beneficial to bacterial hosts, but there are also
      potential costs, which may be considerable in the case of phage infection. Some
      bacterial resistance mechanisms target both beneficial and deleterious forms of
      genetic exchange. Using a general epidemiological model, we explored under which
      conditions such resistance mechanisms may evolve. We considered a population of
      hosts that may be infected by FGEs that either confer a benefit or are
      deleterious to host fitness, and we analysed the epidemiological and evolutionary
      outcomes of resistance evolving under different cost/benefit scenarios. We show
      that the degree of co-infection between these two types of infection is
      particularly important in determining the evolutionarily stable level of host
      resistance. We explore these results using the example of CRISPR-Cas, a form of
      bacterial immunity that targets a variety of FGEs, and we show the potential role
      of bacteriophage infection in selecting for resistance mechanisms that in turn
      limit the acquisition of plasmid-borne antibiotic resistance. Finally, beyond
      microbes, we discuss how endosymbiotic associations may have shaped the evolution
      of host immune responses to pathogens. 

PMID- 24329756
TI  - The current use of Impella 2.5 in acute myocardial infarction complicated by
      cardiogenic shock: results from the USpella Registry.
AB  - OBJECTIVES: To evaluate the periprocedural characteristics and outcomes of
      patients supported with Impella 2.5 prior to percutaneous coronary intervention
      (pre-PCI) versus those who received it after PCI (post-PCI) in the setting of
      cardiogenic shock (CS) complicating an acute myocardial infarction (AMI).
      BACKGROUND: Early mechanical circulatory support may improve outcome in the
      setting of CS complicating an AMI. However, the optimal timing to initiate
      hemodynamic support has not been well characterized. METHODS: Data from 154
      consecutive patients who underwent PCI and Impella 2.5 support from 38 US
      hospitals participating in the USpella Registry were included in our study. The
      primary end-point was survival to discharge. Secondary end-points included
      assessment of patients' hemodynamics and in-hospital complications. A
      multivariate regression model was used to identify independent predictors for
      mortality. RESULTS: Both groups were comparable except for diabetes (P = 0.02),
      peripheral vascular disease (P = 0.008), chronic obstructive pulmonary disease (P
      = 0.05), and prior stroke (P = 0.04), all of which were more prevalent in the pre
      PCI group. Patients in the pre-PCI group had more lesions (P = 0.006) and vessels
      (P = 0.01) treated. These patients had also significantly better survival to
      discharge compared to patients in the post-PCI group (65.1% vs.40.7%, P = 0.003).
      Survival remained favorable for the pre-PCI group after adjusting for potential
      confounding variables. Initiation of support prior to PCI with Impella 2.5 was an
      independent predictor of in-hospital survival (Odds ratio 0.37, 95% confidence
      interval: 0.17-0.79, P = 0.01) in multivariate analysis. The incidence of in
      hospital complications included in the secondary end-point was similar between
      the 2 groups. CONCLUSIONS: The results of our study suggest that early initiation
      of hemodynamic support prior to PCI with Impella 2.5 is associated with more
      complete revascularization and improved survival in the setting of refractory CS
      complicating an AMI.

PMID- 24329757
TI  - Low glutathione regulates gene expression and the redox potentials of the nucleus
      and cytosol in Arabidopsis thaliana.
AB  - Reduced glutathione (GSH) is considered to exert a strong influence on cellular
      redox homeostasis and to regulate gene expression, but these processes remain
      poorly characterized. Severe GSH depletion specifically inhibited root meristem
      development, while low root GSH levels decreased lateral root densities. The
      redox potential of the nucleus and cytosol of Arabidopsis thaliana roots
      determined using roGFP probes was between -300 and -320 mV. Growth in the
      presence of the GSH-synthesis inhibitor buthionine sulfoximine (BSO) increased
      the nuclear and cytosolic redox potentials to approximately -260 mV. GSH
      responsive genes including transcription factors (SPATULA, MYB15, MYB75),
      proteins involved in cell division, redox regulation (glutaredoxinS17,
      thioredoxins, ACHT5 and TH8) and auxin signalling (HECATE), were identified in
      the GSH-deficient root meristemless 1-1 (rml1-1) mutant, and in other GSH
      synthesis mutants (rax1-1, cad2-1, pad2-1) as well as in the wild type following
      the addition of BSO. Inhibition of auxin transport had no effect on organ GSH
      levels, but exogenous auxin decreased the root GSH pool. We conclude that GSH
      depletion significantly increases the redox potentials of the nucleus and
      cytosol, and causes arrest of the cell cycle in roots but not shoots, with
      accompanying transcript changes linked to altered hormone responses, but not
      oxidative stress.

PMID- 24329758
TI  - Expression and in situ localization of GATA4, 5 and 6 mRNAs in ovine conceptuses
      and uterine endometria during the peri-implantation period.
AB  - In vertebrates, six GATA transcription factors, GATA1 through GATA6, have been
      identified and GATA1-3 is known to be involved in hematopoietic developments,
      while GATA4-6 play roles in cardiac and endoderm developments. Recently, we and
      others have found that GATA2 and GATA3 found in the trophectoderm plays a role in
      gene expression specific to this cell type, but GATA4-6 have not been well
      characterized in early embryonic developments. Using quantitative polymerase
      chain reaction (qPCR) and in situ hybridization, we examined the expression of
      GATA4, 5 and 6 messenger RNAs (mRNAs) in ovine conceptuses and uteri during the
      peri-implantation period. In ovine conceptuses, GATA4, 5 and 6 transcripts were
      present on days 15, 17 and 21 (day 0 = day of mating), and high GATA5 and 6 mRNAs
      were found on day 21, most of which were localized in the trophectoderm and
      endoderm. Moreover, minute and substantial GATA4 and 5 mRNAs were found in days
      15 and 21 uterine endometria, respectively. Increase in GATA4-6 transcripts in
      day 21 uteri indicates that in addition to GATA1-3, GATA4-6 may also play a
      potentially novel role in the development of ovine trophectoderm, endoderm and/or
      uterine endometria following conceptus attachment to the uterine epithelium. 

PMID- 24329759
TI  - Volatiles produced by the mycophagous soil bacterium Collimonas.
AB  - It is increasingly recognized that volatile organic compounds play an import role
      during interactions between soil microorganisms. Here, we examined the possible
      involvement of volatiles in the interaction of Collimonas bacteria with soil
      fungi. The genus Collimonas is known for its ability to grow at the expense of
      living fungi (mycophagy), and antifungal volatiles may contribute to the attack
      of fungi by these bacteria. We analyzed the composition of volatiles produced by
      Collimonas on agar under different nutrient conditions and studied the effect on
      fungal growth. The volatiles had a negative effect on the growth of a broad
      spectrum of fungal species. Collimonas bacteria did also produce volatiles in
      sand microcosms supplied with artificial root exudates. The production of
      volatiles in sand microcosms was enhanced by the presence of fungi. The overall
      picture that we get from our study is that antifungal volatiles produced by
      Collimonas could play an important role in realizing its mycophagous lifestyle.
      The current work is also interesting for understanding the ecological relevance
      of volatile production by soil bacteria in general as we found strong influences
      of root exudates composition and incubation conditions on the spectrum of
      volatiles produced. 

PMID- 24329761
TI  - Discharge status and in-hospital mortality in posterior reversible encephalopathy
      syndrome.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome is a serious and
      increasingly recognized disorder, but data from observational studies on outcome
      and mortality in posterior reversible encephalopathy syndrome (PRES) are scarce.
      We aimed to determine the frequency and associations of in-hospital death and
      discharge status in a large cohort of patients with PRES. METHOD: We
      retrospectively reviewed the radiological report databases of our university
      hospitals between January 1999 and March 2011 for patients with PRES. Patients
      fulfilling the criteria for PRES after detailed investigation of clinical charts
      and imaging studies were included. Clinical charts, paraclinical and brain
      imaging data at onset as well as available data on in-hospital mortality and
      discharge status were analyzed. RESULTS: A total of 103 patients were included.
      Five (4.8%) patients died during hospital stay, 27 (26.2%) remained hospitalized
      after discharge. In univariate analyses, significant differences were found
      between patients discharged home from hospital and patients referred to
      rehabilitation or who died in hospital for the following variables: severe edema
      (P = 0.013), etiology of PRES (P = 0.001), altered mental state at onset (P =
      0.003), altered coagulation (P = 0.004), and length of hospital stay >30 days (P
      < 0.001). CONCLUSION: Features of a severe course of PRES such as severe edema
      and altered mental state are significantly more frequent in patients who were
      referred to inpatient rehabilitation or died in hospital. Prospective studies are
      warranted to establish factors that are associated with unfavorable outcome in
      PRES.

PMID- 24329762
TI  - Congenital factor XIII deficiency in Pakistan: characterization of seven families
      and identification of four novel mutations.
AB  - Deficiency of coagulation factor XIII (FXIII) belongs to the rare bleeding
      disorders and its incidence is higher in populations with consanguineous
      marriages. The aims of this study were to characterize patients and relatives
      from seven families with suspected FXIII deficiency from Pakistan and to identify
      the underlying mutations. As a first indicator of FXIII deficiency, a 5M urea
      clot solubility test was used. Plasma FXIII A- and B-subunit antigen levels were
      determined by ELISA. FXIII activity was measured with an incorporation assay.
      Sequencing of all exons and intron/exon boundaries of F13A was performed, and a
      novel splice site defect was confirmed by RT-PCR analysis. Genetic analysis
      revealed six different mutations in the F13A gene. Two splice site mutations were
      detected, a novel c.1460+1G>A mutation in the first nucleotide of intron 11 and a
      previously reported c.2045G>A mutation in the last nucleotide of exon 14. Neither
      of them was expressed at protein level. A novel nonsense mutation in exon 4,
      c.567T>A, p.Cys188X, was identified, leading in homozygous form to severe FXIII
      deficiency. Two novel missense mutations were found in exons 8 and 9, c.1040C>A,
      p.Ala346Asp and c.1126T>C, p.Trp375Arg, and a previously reported missense
      mutation in exon 10, c.1241C>T, p.Ser413Leu. All patients homozygous for these
      missense mutations presented with severe FXIII deficiency. We have analysed a
      cohort of 27 individuals and reported four novel mutations leading to congenital
      FXIII deficiency. 

PMID- 24329760
TI  - The neuroethology of friendship.
AB  - Friendship pervades the human social landscape. These bonds are so important that
      disrupting them leads to health problems, and difficulties forming or maintaining
      friendships attend neuropsychiatric disorders like autism and depression. Other
      animals also have friends, suggesting that friendship is not solely a human
      invention but is instead an evolved trait. A neuroethological approach applies
      behavioral, neurobiological, and molecular techniques to explain friendship with
      reference to its underlying mechanisms, development, evolutionary origins, and
      biological function. Recent studies implicate a shared suite of neural circuits
      and neuromodulatory pathways in the formation, maintenance, and manipulation of
      friendships across humans and other animals. Health consequences and reproductive
      advantages in mammals additionally suggest that friendship has adaptive benefits.
      We argue that understanding the neuroethology of friendship in humans and other
      animals brings us closer to knowing fully what it means to be human. 

PMID- 24329763
TI  - Compound Astragalus and Salvia miltiorrhiza extracts suppress
      hepatocarcinogenesis by modulating transforming growth factor-beta/Smad
      signaling.
AB  - BACKGROUND AND AIM: Previous studies showed Compound Astragalus and Salvia
      miltiorrhiza extract (CASE), extract from Astragalus membranaceus and Salvia
      miltiorhiza, significantly suppresses hepatocellular carcinoma (HCC) in rats
      induced by diethylinitrosamine (DEN), and in vitro experiments further
      demonstrated that CASE's anti-HepG2 cell invasion is associated with transforming
      growth factor-beta (TGF-beta). We hypothesized that CASE's suppression of HCC is
      modulated by TGF-beta/Smad signaling, and we conducted this in vivo study to test
      this hypothesis. METHODS: Rats were divided into the normal control, the DEN
      group, and three CASE (60, 120, and 240 mg/kg) treatment groups. The expression
      of phosphorylation(p) Smad both at C-terminal and linker region, plasminogen
      activator inhibitor 1, and Smad4 and Smad7 of liver tissues were measured and
      compared across the five groups. RESULTS: The positive staining of pSmad2L and
      pSmad3L increased both in hepatoma nodule areas and adjacent relatively normal
      liver tissues in rats treated with DEN, while the positive staining of pSmad2C
      and pSmad3C increased only in relatively normal liver tissues adjacent to
      hepatoma tissues. The elevated expression of pSmad2C, pSmad2L, pSmad3L, Smad4,
      and plasminogen activator inhibitor 1 proteins were suppressed by CASE in a dose
      dependent manner. CASE treatment also significantly reduced the intranuclear
      amounts of pSmad2L and pSmad3L, and upregulated the elevation of pSmad3C positive
      cells and protein expression in a dose-dependent manner. CONCLUSION: The results
      suggest that CASE significantly suppresses HCC progression by mediating TGF
      beta/Smad signaling, especially by modulating Smad3 phosphorylation both at the C
      terminal and linker region.

PMID- 24329764
TI  - Influence of neutralizing antibodies to adalimumab and infliximab on the
      treatment of psoriasis.
AB  - BACKGROUND: Current treatment with biologics has produced dramatic therapeutic
      effects in patients with psoriasis, although these agents occasionally decrease
      in efficacy. One of the main factors responsible for this attenuation is
      attributed to the development of antidrug antibodies (ADAs). OBJECTIVES: To
      analyse the relationship between serum drug concentrations, the presence of ADAs
      and treatment efficacy of adalimumab and infliximab, and to determine the optimal
      use of these biologics. METHODS: This was a 1-year prospective study in the
      dermatology departments of Kobe University Hospital and collaborating hospitals.
      All patients starting a regimen of adalimumab and infliximab for psoriasis were
      included. We measured the serum concentration of the drugs and titres of
      antibodies to adalimumab and infliximab, as well as the Psoriasis Area and
      Severity Index scores at weeks 0, 4, 12, 24 and 48 during the first year of
      treatment. RESULTS: We observed a 50% positive rate of ADAs to adalimumab, and a
      41% positive rate of ADAs to infliximab. The titres of ADAs showed a wide range
      from low to high titres. In the high-titre groups, the patients exhibited a
      decreased clinical response, and demonstrated a negative correlation between
      titre and clinical response. However, an equivalent therapeutic effect was
      observed between the low-titre group and the group with no antibodies detected
      for adalimumab. For infliximab, the patients with ADAs showed decreased clinical
      response. An apparent negative correlation between antibody production and
      reduced clinical response was observed. CONCLUSIONS: Two biologics, adalimumab
      and infliximab, showed different therapeutic behaviour. The measurement of ADAs
      and drug concentrations has important implications for treatment with biologics.

PMID- 24329766
TI  - Comparison of laboratory values obtained via central venous catheters and
      venipuncture for better clinical decisions regarding sampling procedures of
      intensive care unit patients.

PMID- 24329765
TI  - Evaluation of sodium hypochlorite as a denture cleanser: a clinical study.
AB  - OBJECTIVES: To evaluate the effect of sodium hypochlorite (NaOCl) on biofilms,
      colour stability (DeltaE) and surface roughness (Ra) of complete dentures and
      patient acceptability. BACKGROUND: Denture cleansers should be able to reduce the
      accumulation of biofilms without affecting the acrylic resin properties. Patient
      satisfaction is important to maintaining their daily use. MATERIALS AND METHODS:
      Fifteen participants were instructed to keep their dentures immersed daily in a
      0.5% NaOCl solution for 3 min over 90 days. Swabs were taken from dentures and
      inoculated on CHROMagar and blood agar. The number of colony-forming units (cfu)
      was counted after a 48-h incubation period. DeltaE was assessed using the CIE
      L*a*b* system. Ra was measured using a profilometer. Patient acceptability was
      checked based on their degree of satisfaction. Cell counts, DeltaE and Ra were
      analysed using anova, Friedman's and Kruskal-Wallis tests, respectively (alpha =
      0.05). RESULTS: A significant reduction in the total number of microorganisms (p
      = 0.001) and Candida spp. was noticed. No significant differences were found for
      DeltaE (p = 0.68) and for Ra (p = 0.47). The level of the patient satisfaction
      increased throughout the follow-up period. CONCLUSION: The 0.5% NaOCl solution
      was effective in reducing microorganisms without significant changes in colour or
      roughness of denture resin. The participants reported satisfaction with the
      cleaning results.

PMID- 24329767
TI  - Long-term trends in alcohol policy attitudes in Norway.
AB  - INTRODUCTION AND AIMS: The aim of this study was to describe trends in attitudes
      to alcohol control policies in Norway over a period of 50 years and to discuss
      how these trends relate to developments in alcohol policy. DESIGN AND METHODS:
      Survey data from 17 national population surveys, national statistics and previous
      publications were applied to describe trends in attitudes to alcohol control
      polices (access to alcohol and price) and changes in these policies over the
      period 1962 to 2012. RESULTS: From 1962 to 1999, an increasing proportion of the
      population reported that regulations on availability of alcohol were too strict
      and that alcohol prices were too high, whereas in the 2000s this trend was
      reversed and support for existing control policies increased. Although the
      pillars of Norwegian alcohol policy--high prices, restricted access and a state
      monopoly on retail sales-remained, control policies were gradually relaxed
      throughout the entire period. DISCUSSION AND CONCLUSIONS: Relaxation of strict
      alcohol control policies in Norway in the first four decades were probably, in
      part, the result of increasingly liberal public opinion. The subsequent reversed
      trend in opinions with increasing support for control policies may be due to
      several factors, for example, consumer-oriented changes in the monopoly system,
      increased availability and affordability, increased awareness of alcohol-related
      harm and the effectiveness of control policies. Thus, the dynamics of policies
      and attitudes may well change over time.

PMID- 24329768
TI  - The Pseudomonas syringae type III effector HopD1 suppresses effector-triggered
      immunity, localizes to the endoplasmic reticulum, and targets the Arabidopsis
      transcription factor NTL9.
AB  - * Pseudomonas syringae type III effectors are known to suppress plant immunity to
      promote bacterial virulence. However, the activities and targets of these
      effectors are not well understood. * We used genetic, molecular, and cell biology
      methods to characterize the activities, localization, and target of the HopD1
      type III effector in Arabidopsis. * HopD1 contributes to P. syringae virulence in
      Arabidopsis and reduces effector-triggered immunity (ETI) responses but not
      pathogen-associated molecular pattern-triggered immunity (PTI) responses. Plants
      expressing HopD1 supported increased growth of ETI-inducing P. syringae strains
      compared with wild-type Arabidopsis. We show that HopD1 interacts with the
      membrane-tethered Arabidopsis transcription factor NTL9 and demonstrate that this
      interaction occurs at the endoplasmic reticulum (ER). A P. syringae hopD1 mutant
      and ETI-inducing P. syringae strains exhibited enhanced growth on Arabidopsis
      ntl9 mutant plants. Conversely, growth of P. syringae strains was reduced in
      plants expressing a constitutively active NTL9 derivative, indicating that NTL9
      is a positive regulator of plant immunity. Furthermore, HopD1 inhibited the
      induction of NTL9-regulated genes during ETI but not PTI. * HopD1 contributes to
      P. syringae virulence in part by targeting NTL9, resulting in the suppression of
      ETI responses but not PTI responses and the promotion of plant pathogenicity.

PMID- 24329769
TI  - Novel techniques for enhancement and segmentation of acne vulgaris lesions.
AB  - BACKGROUND: More than 99% acne patients suffer from acne vulgaris. While
      diagnosing the severity of acne vulgaris lesions, dermatologists have observed
      inter-rater and intra-rater variability in diagnosis results. This is because
      during assessment, identifying lesion types and their counting is a tedious job
      for dermatologists. To make the assessment job objective and easier for
      dermatologists, an automated system based on image processing methods is proposed
      in this study. OBJECTIVES: There are two main objectives: (i) to develop an
      algorithm for the enhancement of various acne vulgaris lesions; and (ii) to
      develop a method for the segmentation of enhanced acne vulgaris lesions. METHODS:
      For the first objective, an algorithm is developed based on the theory of high
      dynamic range (HDR) images. The proposed algorithm uses local rank transform to
      generate the HDR images from a single acne image followed by the log
      transformation. Then, segmentation is performed by clustering the pixels based on
      Mahalanobis distance of each pixel from spectral models of acne vulgaris lesions.
      RESULTS: Two metrics are used to evaluate the enhancement of acne vulgaris
      lesions, i.e., contrast improvement factor (CIF) and image contrast normalization
      (ICN). The proposed algorithm is compared with two other methods. The proposed
      enhancement algorithm shows better result than both the other methods based on
      CIF and ICN. In addition, sensitivity and specificity are calculated for the
      segmentation results. The proposed segmentation method shows higher sensitivity
      and specificity than other methods. CONCLUSION: This article specifically
      discusses the contrast enhancement and segmentation for automated diagnosis
      system of acne vulgaris lesions. The results are promising that can be used for
      further classification of acne vulgaris lesions for final grading of the lesions.

PMID- 24329770
TI  - Mechanisms regulating auxin action during fruit development.
AB  - Auxin controls many aspects of fruit development, including fruit set and growth,
      ripening and abscission. However, the mechanisms by which auxin regulates these
      processes are still poorly understood. While it is generally agreed that precise
      spatial and temporal control of auxin distribution and signaling are required for
      fruit development, the dynamics of auxin biosynthesis and the mechanisms for its
      transport to different fruit tissues are mostly unknown. Despite major advances
      in elucidating many aspects of auxin biology in vegetative tissues, until
      recently, the nature and importance of auxin metabolism, transport and signaling
      during fruit ontogeny remained obscure. In this review, we summarize recent
      research that has started to elucidate the molecular mechanisms by which auxin is
      produced and transported in the fruit and to unravel the complexity of auxin
      signaling during fruit development. We also discuss recent approaches used to
      reveal the genes and regulatory networks that mediate cell and tissue-specific
      control of auxin levels in the developing fruit. 

PMID- 24329771
TI  - Transcription activator-like effector nucleases efficiently disrupt the target
      gene in Iberian ribbed newts (Pleurodeles waltl), an experimental model animal
      for regeneration.
AB  - Regeneration of a lost tissue in an animal is an important issue. Although
      regenerative studies have a history of research spanning more than a century, the
      gene functions underlying regulation of the regeneration are mostly unclear.
      Analysis of knockout animals is a very powerful tool with which to elucidate gene
      function. Recently, transcription activator-like effector nucleases (TALENs) have
      been developed as an effective technique for genome editing. This technique
      enables gene targeting in amphibians such as newts that were previously
      impossible. Here we show that newts microinjected with TALEN mRNAs designed for
      targeting the tyrosinase gene in single-cell stage embryos revealed an albino
      phenotype. Sequence analysis revealed that the tyrosinase genes were effectively
      disrupted in these albino newts. Moreover, precise genome alteration was achieved
      using TALENs and single strand oligodeoxyribonucleotides. Our results suggest
      that TALENs are powerful tools for genome editing for regenerative research in
      newts. 

PMID- 24329772
TI  - Inflammation-related cytokines in oral lichen planus: an overview.
AB  - Cytokines are powerful mediators which play a central role in both innate and
      adapted immune responses. Aberrant productions of cytokines may lead to the onset
      of immune deficiency, allergy or autoimmunity, which are involved in the
      mechanisms of various immune-mediated inflammatory diseases. Oral lichen planus
      (OLP) is a chronic inflammation disease affecting the oral mucosa with unknown
      aetiology. Previous studies have described the abnormal expression patterns of
      various inflammation-related cytokines, such as IL-1, 2, 4, 5, 6, 8, 10, 12, 17,
      18, TGF-beta, IFN-gamma and TNF-alpha, in lesions, saliva, serum and peripheral
      blood mononuclear cells from patients with OLP, which may reflect the immune
      dysregulation status and emerge as central players in the immunopathogenesis of
      OLP. Besides, the gene polymorphisms of several cytokines such as IFN-gamma, TNF
      alpha, IL-4, IL-10 have been found to be involved in the susceptibility of OLP.
      In this review, we gave a brief introduction of the characteristics and
      biological functions of these inflammation-related cytokines and summarized for
      the first time the current knowledge on the involvement of inflammation-related
      cytokines in OLP. Further research on the exact roles of these cytokines will aid
      the understanding of the pathogenesis and the identification of novel therapeutic
      approaches of OLP. 

PMID- 24329773
TI  - A model of laboratory surveillance for neuro-arbovirosis applied during 2012 in
      the Emilia-Romagna region, Italy.
AB  - Arboviruses with neuroinvasive potential are gaining more attention due to the
      increased number of cases of autochthonous and imported infections in the human
      host. Diagnosis of infection caused by these viruses in patients with central
      nervous system (CNS) diseases is still underestimated and these infections
      represent an emerging threat to public health. We describe a model suitable for
      the laboratory surveillance of neuro-arbovirosis that was applied in the Emilia
      Romagna region, north-eastern Italy, during the 2012 summer season. One hundred
      and twenty cases of suspected neuroinvasive infection were tested for arboviral
      agents on the basis of clinical and laboratory signs and epidemiological data.
      The most common virus detected was Toscana virus (TOSV): anti-TOSV specific
      antibodies or viral components were detected in 28.3% of the cases; 79.4% of the
      TOSV cases were in the acute phase of infection. No cases resulted in acute phase
      for West Nile (WNV), Usutu (USUV), Chikungunya (CHIKV) or Dengue (DENV) virus
      infection. Conversely, two patients with a history of staying in a tick-borne
      encephalitis virus (TBEV) endemic area showed a probable TBEV infection. These
      results emphasize the importance of a complete and 'ready to act' laboratory
      diagnostic system to be implemented within the larger frame of a regional
      integrated surveillance system.

PMID- 24329774
TI  - Costs and benefits linked to developments in cognitive control.
AB  - Developing cognitive control over one's thoughts, emotions, and actions is a
      fundamental process that predicts important life outcomes. Such control begins in
      infancy, and shifts during development from a predominantly reactive form (e.g.
      retrieving task-relevant information when needed) to an increasingly proactive
      form (e.g. maintaining task-relevant information in anticipation of needing it).
      While such developments are generally viewed as adaptive, cognitive abilities can
      also involve trade-offs, such that the benefits of developing increasingly
      proactive control may come with associated costs. In two experiments, we test for
      such cognitive trade-offs in children who are transitioning to proactive control.
      We find that proactive control predicts expected benefits in children's working
      memory, but is also associated with predicted costs in disproportionately slowing
      children under conditions of distraction. These findings highlight unique
      advantages and disadvantages of proactive and reactive control, and suggest
      caution in attempting to alter their balance during development. 

PMID- 24329775
TI  - The role of phylogeny and ecology in shaping morphology in 21 genera and 127
      species of Australo-Papuan myobatrachid frogs.
AB  - Body shape is predicted to differ among species for functional reasons and in
      relation to environmental niche and phylogenetic history. We quantified
      morphological differences in shape and size among 98.5% of the 129 species and
      all 21 genera of the Australo-Papuan endemic myobatrachid frogs to test the
      hypothesis that habitat type predicts body shape in this radiation. We tested
      this hypothesis in a phylogenetic context at two taxonomic levels: across the
      entire radiation and within the four largest genera. Thirty-four external
      measurements were taken on 623 museum specimens representing 127 species. Data
      for seven key environmental variables relevant to anurans were assembled for all
      Australian-distributed species based on species' distributions and 131,306
      locality records. The Australo-Papuan myobatrachid radiation showed high
      diversity in adult body size, ranging from minute (15 mm snout-vent length) to
      very large species (92 mm), and shape, particularly sin relative limb length.
      Five main morphological and environmental summary variables displayed strong
      phylogenetic signal. There was no clear relationship between body size and
      environmental niche, and this result persisted following phylogenetic correction.
      For most species, there was a better match between environment/habitat and body
      shape, but this relationship did not persist following phylogenetic correction.
      At a broad level, species fell into three broad groups based on environmental
      niche and body shape: 1) species in wet habitats with relatively long limbs, 2)
      species in arid environments with relatively short limbs (many of which are
      forward or backward burrowers) and 3) habitat generalist species with a
      conservative body shape. However, these patterns were not repeated within the
      four largest genera - Crinia, Limnodynastes, Pseudophryne and Uperoleia. Each of
      these genera displayed a highly conservative anuran body shape, yet individual
      species were distributed across the full spectrum of Australian environments. Our
      results suggest that phylogenetic legacy is important in the evolution of body
      size and shape in Australian anurans, but also that the conservative body plan of
      many frogs works well in a wide variety of habitats. 

PMID- 24329776
TI  - Conversion of stable ABO-incompatible kidney transplant recipients from
      mycophenolate mofetil with standard exposure calcineurin inhibitors (CNIs) to
      everolimus with very low exposure CNIs-a short-term pilot study.
AB  - BACKGROUND: A recent report has demonstrated that as with mycophenolate mofetil
      (MMF), everolimus is capable of inhibiting human B-lymphocyte function and
      activation including B-lymphocyte proliferation, apoptosis, and immunoglobulin
      production in vitro. Everolimus may therefore be used as an immunosuppressant in
      ABO-incompatible kidney transplantation. METHODS: A three-month pilot study was
      performed to examine the efficacy and safety of conversion of stable ABO
      incompatible kidney transplant recipients from MMF with standard exposure
      calcineurin inhibitors (CNIs) to everolimus with very low exposure CNIs. Sixteen
      recipients were enrolled in the study. The patients without acute rejection by
      graft biopsy were switched from MMF to everolimus with CNI minimization. At three
      months after conversion, graft biopsies were performed to check for acute
      rejection and C4d deposition. RESULTS: Conversion to everolimus with CNI
      minimization for three months did not induce acute rejection and C4d deposition
      in all of the ABO-incompatible kidney transplant recipients. A slight elevation
      of anti-A/B antibody titer occurred in our present study. Everolimus was
      associated with hyperlipidemia and edema. CONCLUSIONS: These results demonstrated
      that short-term conversion from MMF to everolimus after one yr post-transplant
      may be a safe and effective alternate for ABO-incompatible kidney transplant
      recipients requiring temporary discontinuation of MMF.

PMID- 24329777
TI  - Changes in factor XIII level during pregnancy.
AB  - Pregnancy is associated with significant haemostatic changes, with a progressive
      rise in most clotting factors. There is limited data on the changes of factor
      XIII (FXIII) level during pregnancy. This study assesses changes in FXIII
      activity during normal pregnancy and establish FXIII reference range during each
      trimester of pregnancy and immediate postnatal period. This is a cross sectional
      study of 376 women with normal uneventful pregnancies. Plasma FXIII activity was
      measured during first (weeks 0-12, n = 116), second (weeks 13-28, n = 132), third
      trimester (weeks 29-42, n = 128) and postnatal (day 0-3; n = 30). Samples were
      also collected from non-pregnant women (n = 25) as a control group. FXIII was
      assayed on CS-5100 analyser using chromogenic reagent. The mean +/- SD FXIII
      activity was 112 +/- 29 IU dL(-1) during first trimester, 96 +/- 26 IU dL(-1)
      during second trimester, 83 +/- 21 IU dL(-1) during third trimester, 90 +/- 19 IU
      dL(-1) during postnatal period, and 113 +/- 26 IU dL(-1) in the control. The
      reference range was calculated during the first (55-169 IU dL(-1)), second (45
      147 IU dL(-1)), third trimester (42-125 IU dL(-1)) and postnatal period (61-137
      IU dL(-1)). There was a significant reduction in the mean FXIII activity during
      the second and third trimester compared to the first trimester and control group
      (P < 0.0001). During the immediate postnatal period, the mean FXIII activity was
      not statistically different compared to the third and second trimester levels but
      was significantly lower compared to the first trimester (P < 0.0001) level and
      the control group (P = 0.0002). This study establishes the reference range for
      FXIII activity during the three trimesters of normal pregnancy and immediate
      postnatal period. Women have a significantly decreased level of FXIII activity
      during a normal uneventful pregnancy.

PMID- 24329778
TI  - Prenatal exposure to the CB1 and CB2 cannabinoid receptor agonist WIN 55,212-2
      alters migration of early-born glutamatergic neurons and GABAergic interneurons
      in the rat cerebral cortex.
AB  - The endocannabinoid system, composed of cannabinoid receptors, endocannabinoids,
      and synthesis and degradation enzymes, is present since early stages of brain
      development. During this period, the endocannabinoid system is involved in the
      regulation of neural progenitor proliferation and specification as well as the
      migration and differentiation of pyramidal neurons and interneurons. Marijuana
      consumption during pregnancy represents a serious risk in relation to the fetal
      brain development since Delta(9) -tetrahidrocannabinol, the main active compound
      of cannabis, can reach the fetus through placenta and hemato-encephalic barrier.
      Cohort studies performed on children and adolescents of mothers who consumed
      marijuana during pregnancy reported cognitive and comportamental abnormalities.
      In the present study, we examined the expression of the cannabinoid receptor CB1
      R during corticogenesis in radially and tangentially migrating post-mitotic
      neurons. We found that prenatal exposure to WIN impaired tangential and radial
      migration of post-mitotic neurons in the dorsal pallium. In addition, we
      described alterations of two transcription factors associated with proliferating
      and newly post-mitotic glutamatergic cells in the dorsal pallium, Tbr1 and Tbr2,
      and disruption in the number of Cajal-Retzius cells. The present results
      contribute to the knowledge of neurobiological substrates that determine neuro
      comportamental changes that will persist through post-natal life.

PMID- 24329779
TI  - Effects of hypothalamic dopamine (DA) on salsolinol (SAL)-induced prolactin (PRL)
      secretion in male goats.
AB  - The aim of the present study was to clarify the effects of hypothalamic dopamine
      (DA) on salsolinol (SAL)-induced prolactin (PRL) release in goats. The PRL
      releasing response to an intravenous (i.v.) injection of SAL was examined after
      treatment with augmentation of central DA using carbidopa (carbi) and L-dopa in
      male goats under 8-h (8 h light, 16 h dark) or 16-h (16 h light, 8 h dark)
      photoperiod conditions. The carbi and L-dopa treatments reduced basal PRL
      concentrations in the 16-h photoperiod group (P < 0.05), while a reduction was
      not observed in the 8-h photoperiod group. The mean basal plasma PRL
      concentration in the control group for the 8-h photoperiod was lower than that
      for the 16-h photoperiod (P < 0.05). SAL significantly stimulated the release of
      PRL promptly after the injection in both the 8- and 16-h photoperiod groups (P <
      0.05). PRL-releasing responses for the 16-h photoperiod were greater than those
      for the 8-h photoperiod (P < 0.05). The carbi and L-dopa treatments blunted SAL
      induced PRL release in both the 8- and 16-h photoperiods (P < 0.05). These
      results indicate that hypothalamic DA blunts the SAL-induced release of PRL in
      male goats, regardless of the photoperiod, which suggests that both SAL and DA
      are involved in regulating the secretion of PRL in goats. 

PMID- 24329780
TI  - Sulfaphenazole and alpha-naphthoflavone attenuate the metabolism of the synthetic
      cannabinoids JWH-018 and AM2201 found in K2/spice.
AB  - "K2" or "Spice" is an emerging drug of abuse that is laced with psychoactive
      synthetic cannabinoids JWH-018 and AM2201. Previous studies have identified
      hydroxylated (OH) and carboxylated (COOH) species as primary human metabolites,
      and kinetic studies have implicated CYP2C9 and -1A2 as major hepatic P450s
      involved in JWH-018 and AM2201 oxidation. The present study extends these
      findings by testing the hypothesis that CYP2C9- and 1A2-selective chemical
      inhibitors, sulfaphenazole (SFZ) and alpha-naphthoflavone (ANF), block oxidation
      of JWH-018 and AM2201 in human liver microsomes (HLM). A concentration-dependent
      inhibition of JWH-018 and AM2201 oxidation was observed in the presence of
      increasing concentration of SFZ (0.5 - 50 MUM) and ANF (0.1 - 5.0 MUM). No
      metabolic inhibition was observed with omeprazole, quinidine, and ketoconazole.
      The results presented herein further demonstrate the importance of CYP2C9- and
      1A2-mediated oxidation of JWH-018 and AM2201 and the likelihood of adverse
      toxicity in populations with polymorphic alleles of these enzymes. 

PMID- 24329781
TI  - Ovarian carcinoma histotype determination is highly reproducible, and is improved
      through the use of immunohistochemistry.
AB  - AIMS: To assess the variation in ovarian carcinoma type diagnosis among
      gynaecological pathologists from Nordic countries, and whether a rationally
      designed panel of immunohistochemical markers could improve diagnostic
      reproducibility. METHODS AND RESULTS: Eight pathologists from four countries
      (Sweden, Denmark, Norway, and Finland) received an educational lecture on the
      diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian
      carcinoma cases were independently reviewed by the participants, who: (i)
      determined type purely on the basis of histology; (ii) indicated whether they
      would apply immunohistochemistry in their routine practice; and (iii) determined
      type after reviewing the staining results. The results for six markers (WT1, p53,
      p16, HNF-1beta, ARID1A, and progesterone receptor) were determined for all 54
      cases, by staining of a tissue microarray. The median concordance with central
      review diagnosis was 86%, and significantly improved to 90% with the
      incorporation of immunostaining results (P = 0.0002). The median interobserver
      agreement was 78%, and significantly improved to 85% with the incorporation of
      immunostaining results (P = 0.0002). CONCLUSIONS: Use of the immunostaining
      results significantly improved both diagnostic accuracy and interobserver
      agreement. These results indicate that ovarian carcinoma type can be reliably
      diagnosed by pathologists from different countries, and also demonstrate that
      immunohistochemistry has an important role in improving diagnostic accuracy and
      agreement between pathologists.

PMID- 24329782
TI  - Full-thickness skin grafts for surgical defects of the nasal ala - a
      comprehensive review, approach and outcomes of 186 cases over 9 years.
AB  - BACKGROUND: Skin cancers of the nasal ala are commonly encountered in
      dermatological surgery. Various techniques have been described to reconstruct
      surgical defects of the ala, including melolabial transposition flaps,
      interpolated melolabial flaps, bilobed and trilobed transposition flaps, island
      pedicle flaps and spiral flaps. Full-thickness skin grafts have received little
      attention in the reconstructive literature. OBJECTIVES: We present our experience
      with full-thickness skin grafts for the reconstruction of partial thickness
      defects of the nasal ala in the largest series to date. METHODS: A retrospective
      analysis of the Mohs micrographic surgery database over a 9-year period was
      performed. All cases of full-thickness skin grafts for reconstruction of the
      nasal ala were identified. Defect location, size and any postoperative
      complications were noted. All patients were reviewed at the time of suture
      removal, at 3 and 6 weeks postoperatively and at 1 year. RESULTS: There were 186
      cases in total in 181 patients (88 men and 93 women). Their ages ranged from 31
      to 88 years with a mean of 65 years (median 66). Defect size varied from 0.3 *
      0.4 cm to 2.0 * 2.7 cm, with the average defect size measuring 1.0-1.2 cm in
      diameter. Thirty-six per cent (67 of 186) of cases underwent postoperative
      dermabrasion, and 8% (14 of 186) received postoperative intralesional
      triamcinolone. The incidence of graft failure and infection was low. Good-to
      excellent cosmetic results were seen in all patients and postoperative
      complications were uncommon and minor. CONCLUSIONS: The use of full-thickness
      skin grafts for defects of the nasal ala is a simple and versatile reconstructive
      option with excellent functional and aesthetic outcomes.

PMID- 24329783
TI  - Healthcare needs of older Arab migrants: a systematic review.
AB  - AIMS AND OBJECTIVES: To explore the healthcare needs of older Arab migrants,
      focussing on Arab-Australians and their socio-cultural characteristics.
      BACKGROUND: Disparities in accessing healthcare services and addressing
      healthcare needs are evident among ethnic minorities including Arab migrants,
      particularly, older people. Racial stereotyping can also affect their ability to
      use these services. Arabs are a populous and diverse group with a long history of
      global migration. Australia is one of the most multicultural societies in the
      world, and Arab-Australians constitute an important ethnic minority group.
      DESIGN: Systematic review. METHODS: The electronic databases Academic Search
      Complete (EBSCO), MEDLINE (Ovid), Ageline, ProQuest, CINAHL, PubMed, PsychINFO
      and Google Scholar were searched from 1990-October 2012. Search terms included
      health care needs, aged care, ethnic, cultural, linguistics, social, ethnic
      groups, culturally and linguistically diverse, nonEnglish speaking, ageing,
      elderly, Arabs, Arabic-speaking and Australia. RESULTS: Eight articles reviewing
      the healthcare issues of Australians from Arabic-speaking background were
      identified using the search strategy. An additional eight articles were
      identified through hand searching. CONCLUSIONS: Racial stereotyping can alter
      health-seeking behaviours and healthcare treatment. Increasing the understanding
      of specific cultural attributes of Arab-Australians will contribute to improving
      health outcomes. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers and
      policymakers need to adopt more effective ways of communication with Arab
      Australians to provide more culturally competent care and achieve better health
      outcomes.

PMID- 24329784
TI  - Preview of Immunological Reviews for 2014.

PMID- 24329785
TI  - Video podcast: Adoptive immunotherapy for cancer.

PMID- 24329787
TI  - Adoptive immunotherapy for cancer.
AB  - Recent clinical success has underscored the potential for immunotherapy based on
      the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic,
      potent, and durable clinical responses. This success has led to the broader
      evaluation of engineered T-lymphocyte-based adoptive cell therapy to treat a
      broad range of malignancies. In this review, we summarize concepts, successes,
      and challenges for the broader development of this promising field, focusing
      principally on lessons gleaned from immunological principles and clinical
      thought. We present ACT in the context of integrating T-cell and tumor biology
      and the broader systemic immune response. 

PMID- 24329786
TI  - Engineering T cells for cancer: our synthetic future.

PMID- 24329790
TI  - TCR repertoires of intratumoral T-cell subsets.
AB  - The infiltration of human tumors by T cells is a common phenomenon, and over the
      past decades, it has become increasingly clear that the nature of such
      intratumoral T-cell populations can predict disease course. Furthermore,
      intratumoral T cells have been utilized therapeutically in clinical studies of
      adoptive T-cell therapy. In this review, we describe how novel methods that are
      either based on T-cell receptor (TCR) sequencing or on cancer exome analysis
      allow the analysis of the tumor reactivity and antigen-specificity of the
      intratumoral TCR repertoire with unprecedented detail. Furthermore, we discuss
      studies that have started to utilize these techniques to probe the link between
      cancer exomes and the intratumoral TCR pool. Based on the observation that both
      the cancer epitope repertoire and intratumoral TCR repertoire appear highly
      individual, we outline strategies, such as 'autologous TCR gene therapy', that
      exploit the tumor-resident TCR repertoire for the development of personalized
      immunotherapy. 

PMID- 24329788
TI  - T lymphocytes targeting native receptors.
AB  - The adoptive transfer of T cells specific for native tumor antigens (TAs) is an
      increasingly popular cancer treatment option because of the ability of these
      cells to discriminate between normal and tumor tissues and the corresponding lack
      of short or long-term toxicities. Infusions of antigen-specific CD4(+) and CD8(+)
      T cells targeting viral antigens derived from Epstein-Barr virus (EBV) induce
      sustained complete tumor remissions in patients with highly immunogenic tumors
      such as post-transplant lymphoproliferative disease, although resistance occurred
      when the infused T-cell population had restricted antigen specificity. T cells
      specific for EBV antigens have also produced complete remissions of EBV-positive
      nasopharyngeal carcinomas and lymphomas developing in immunocompetent
      individuals, even though in these patients tumor survival is dependent on their
      ability to evade T-cell immunity. Adapting this strategy to non-viral tumors is
      more challenging, as the target antigens expressed are less immunogenic and the
      tumors lack the potent danger signals that are characteristic of viruses. The
      goals of current studies are to define conditions that promote expansion of
      antigen-specific T cells ex vivo and to ensure their in vivo persistence and
      survival by combining with maneuvers such as lymphodepletion, checkpoint
      inhibition, cytokine infusions, or genetic manipulations. More pragmatic goals
      are to streamline manufacturing to facilitate the transition of these therapies
      to late phase trials and to evaluate closely histocompatibility antigen (HLA)
      matched banked antigen-specific T cells so that T-cell therapies can be made more
      broadly available. 

PMID- 24329791
TI  - Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an
      inducible cytokine to modulate the tumor stroma.
AB  - Adoptive T-cell therapy recently achieved impressive efficacy in early phase
      trials, in particular in hematologic malignancies, strongly supporting the notion
      that the immune system can control cancer. A current strategy of favor is based
      on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen
      receptor (CAR) and recognize a predefined target by an antibody-derived binding
      domain. Such CAR T cells can substantially reduce the tumor burden as long as the
      targeted antigen is present on the cancer cells. However, given the tremendous
      phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells
      are not recognized by a given CAR, considerably reducing the therapeutic success.
      This article reviews a recently described strategy for overcoming this
      shortcoming of the CAR T-cell therapy by modulating the tumor stroma by a CAR T
      cell-secreted transgenic cytokine like interleukin-12 (IL-12). The basic process
      is that CAR T cells, when activated by their CAR, deposit IL-12 in the targeted
      tumor lesion, which in turn attracts an innate immune cell response toward those
      cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected
      for universal cytokine-mediated killing, exhibited remarkable efficacy against
      solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in
      clinical trials. 

PMID- 24329789
TI  - Exploiting the curative potential of adoptive T-cell therapy for cancer.
AB  - Adoptive T-cell therapy (ACT) is a potent and flexible cancer treatment modality
      that can induce complete, durable regression of certain human malignancies. Long
      term follow-up of patients receiving tumor-infiltrating lymphocytes (TILs) for
      metastatic melanoma reveals a substantial subset that experienced complete,
      lasting tumor regression - and may be cured. Increasing evidence points to
      mutated gene products as the primary immunological targets of TILs from
      melanomas. Recent technological advances permit rapid identification of the
      neoepitopes resulting from these somatic gene mutations and of T cells with
      reactivity against these targets. Isolation and adoptive transfer of these T
      cells may improve TIL therapy for melanoma and permit its broader application to
      non-melanoma tumors. Extension of ACT to other malignancies may also be possible
      through antigen receptor gene engineering. Tumor regression has been observed
      following transfer of T cells engineered to express chimeric antigen receptors
      against CD19 in B-cell malignancies or a T-cell receptor against NY-ESO-1 in
      synovial cell sarcoma and melanoma. Herein, we review recent clinical trials of
      TILs and antigen receptor gene therapy for advanced cancers. We discuss lessons
      from this experience and consider how they might be applied to realize the full
      curative potential of ACT. 

PMID- 24329792
TI  - CAR T cells: driving the road from the laboratory to the clinic.
AB  - Blockbuster antibody therapies have catapulted immune-based approaches to treat
      cancer into the consciousness of mainstay clinical research. On the back of this,
      other emerging immune-based therapies are providing great promise. T-cell therapy
      is one such area where recent trials using T cells genetically modified to
      express an antibody-based chimeric antigen receptor (CAR) targeted against the
      CD19 antigen have demonstrated impressive responses when adoptively transferred
      to patients with advanced chronic lymphocytic leukemia. The general concept of
      the CAR T cell was devised some 20 years ago. In this relatively short period of
      time, the technology to redirect T-cell function has moved at pace facilitating
      clinical translation; however, many questions remain with respect to developing
      the approach to improve CAR T-cell therapeutic activity and also to broaden the
      range of tumors that can be effectively targeted by this approach. This review
      highlights some of the underlying principles and compromises of CAR T-cell
      technology using the CD19-targeted CAR as a paradigm and discusses some of the
      issues that relate to targeting solid tumors with CAR T cells.

PMID- 24329793
TI  - Design and development of therapies using chimeric antigen receptor-expressing T
      cells.
AB  - Investigators developed chimeric antigen receptors (CARs) for expression on T
      cells more than 25 years ago. When the CAR is derived from an antibody, the
      resultant cell should combine the desirable targeting features of an antibody
      (e.g. lack of requirement for major histocompatibility complex recognition,
      ability to recognize non-protein antigens) with the persistence, trafficking, and
      effector functions of a T cell. This article describes how the past two decades
      have seen a crescendo of research which has now begun to translate these
      potential benefits into effective treatments for patients with cancer. We
      describe the basic design of CARs, describe how antigenic targets are selected,
      and the initial clinical experience with CAR-T cells. Our review then describes
      our own and other investigators' work aimed at improving the function of CARs and
      reviews the clinical studies in hematological and solid malignancies that are
      beginning to exploit these approaches. Finally, we show the value of adding
      additional engineering features to CAR-T cells, irrespective of their target, to
      render them better suited to function in the tumor environment, and discuss how
      the safety of these heavily modified cells may be maintained.

PMID- 24329796
TI  - Adoptive immunotherapy with genetically modified lymphocytes in allogeneic stem
      cell transplantation.
AB  - Hematopoietic stem cell transplantation from a healthy donor (allo-HSCT)
      represents the most potent form of cellular adoptive immunotherapy to treat
      malignancies. In allo-HSCT, donor T cells are double edge-swords: highly potent
      against residual tumor cells, but potentially highly toxic, and responsible for
      graft versus host disease (GVHD), a major clinical complication of
      transplantation. Gene transfer technologies coupled with current knowledge on
      cancer immunology have generated a wide range of approaches aimed at fostering
      the immunological response to cancer cells, while avoiding or controlling GVHD.
      In this review, we discuss cell and gene therapy approaches currently tested in
      preclinical models and in clinical trials. 

PMID- 24329794
TI  - Design and implementation of adoptive therapy with chimeric antigen receptor
      modified T cells.
AB  - A major advance in adoptive T-cell therapy (ACT) is the ability to efficiently
      endow patient's T cells with reactivity for tumor antigens through the stable or
      regulated introduction of genes that encode high affinity tumor-targeting T-cell
      receptors (TCRs) or synthetic chimeric antigen receptors (CARs). Case reports and
      small series of patients treated with TCR- or CAR-modified T cells have shown
      durable responses in a subset of patients, particularly with B-cell malignancies
      treated with T cells modified to express a CAR that targets the CD19 molecule.
      However, many patients do not respond to therapy and serious on and off-target
      toxicities have been observed with TCR- and CAR-modified T cells. Thus,
      challenges remain to make ACT with gene-modified T cells a reproducibly effective
      and safe therapy and to expand the breadth of patients that can be treated to
      include those with common epithelial malignancies. This review discusses research
      topics in our laboratories that focus on the design and implementation of ACT
      with CAR-modified T cells. These include cell intrinsic properties of distinct T
      cell subsets that may facilitate preparing therapeutic T-cell products of defined
      composition for reproducible efficacy and safety, the design of tumor targeting
      receptors that optimize signaling of T-cell effector functions and facilitate
      tracking of migration of CAR-modified T cells in vivo, and novel CAR designs that
      have alternative ligand binding domains or confer regulated function and/or
      survival of transduced T cells. 

PMID- 24329795
TI  - Re-adapting T cells for cancer therapy: from mouse models to clinical trials.
AB  - Adoptive T-cell therapy involves the isolation, expansion, and reinfusion of T
      lymphocytes with a defined specificity and function as a means to eradicate
      cancer. Our research has focused on specifying the requirements for tumor
      eradication with antigen-specific T cells and T cells transduced to express a
      defined T-cell receptor (TCR) in mouse models and then translating these
      strategies to clinical trials. Our design of T-cell-based therapy for cancer has
      reflected efforts to identify the obstacles that limit sustained effector T-cell
      activity in mice and humans, design approaches to enhance T-cell persistence,
      develop methods to increase TCR affinity/T-cell functional avidity, and pursue
      strategies to overcome tolerance and immunosuppression. With the advent of
      genetic engineering, a highly functional population of T cells can now be rapidly
      generated and tailored for the targeted malignancy. Preclinical studies in
      faithful and informative mouse models, in concert with knowledge gained from
      analyses of successes and limitations in clinical trials, are shaping how we
      continue to develop, refine, and broaden the applicability of this approach for
      cancer therapy. 

PMID- 24329797
TI  - A new approach to gene therapy using Sleeping Beauty to genetically modify
      clinical-grade T cells to target CD19.
AB  - The advent of efficient approaches to the genetic modification of T cells has
      provided investigators with clinically appealing methods to improve the potency
      of tumor-specific clinical grade T cells. For example, gene therapy has been
      successfully used to enforce expression of chimeric antigen receptors (CARs) that
      provide T cells with ability to directly recognize tumor-associated antigens
      without the need for presentation by human leukocyte antigen. Gene transfer of
      CARs can be undertaken using viral-based and non-viral approaches. We have
      advanced DNA vectors derived from the Sleeping Beauty (SB) system to avoid the
      expense and manufacturing difficulty associated with transducing T cells with
      recombinant viral vectors. After electroporation, the transposon/transposase
      improves the efficiency of integration of plasmids used to express CAR and other
      transgenes in T cells. The SB system combined with artificial antigen-presenting
      cells (aAPC) can selectively propagate and thus retrieve CAR(+) T cells suitable
      for human application. This review describes the translation of the SB system and
      aAPC for use in clinical trials and highlights how a nimble and cost-effective
      approach to developing genetically modified T cells can be used to implement
      clinical trials infusing next-generation T cells with improved therapeutic
      potential. 

PMID- 24329798
TI  - Human cell-based artificial antigen-presenting cells for cancer immunotherapy.
AB  - Adoptive T-cell therapy, where anti-tumor T cells are first prepared in vitro, is
      attractive since it facilitates the delivery of essential signals to selected
      subsets of anti-tumor T cells without unfavorable immunoregulatory issues that
      exist in tumor-bearing hosts. Recent clinical trials have demonstrated that anti
      tumor adoptive T-cell therapy, i.e. infusion of tumor-specific T cells, can
      induce clinically relevant and sustained responses in patients with advanced
      cancer. The goal of adoptive cell therapy is to establish anti-tumor immunologic
      memory, which can result in life-long rejection of tumor cells in patients. To
      achieve this goal, during the process of in vitro expansion, T-cell grafts used
      in adoptive T-cell therapy must be appropriately educated and equipped with the
      capacity to accomplish multiple, essential tasks. Adoptively transferred T cells
      must be endowed, prior to infusion, with the ability to efficiently engraft,
      expand, persist, and traffic to tumor in vivo. As a strategy to consistently
      generate T-cell grafts with these capabilities, artificial antigen-presenting
      cells have been developed to deliver the proper signals necessary to T cells to
      enable optimal adoptive cell therapy. 

PMID- 24329799
TI  - Rapamycin-resistant effector T-cell therapy.
AB  - Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) represents
      a stress test for tumor cells and T cells. Mechanisms exist that allow cells to
      survive this stress, including suboptimal target block, alternative signaling
      pathways, and autophagy. Rapamycin-resistant effector T (T-Rapa) cells have an
      altered phenotype that associates with increased function. Ex vivo rapamycin,
      when used in combination with polarizing cytokines and antigen-presenting-cell
      free costimulation, is a flexible therapeutic approach as polarization to T
      helper 1 (Th1)- or Th2-type effectors is possible. Murine T-Rapa cells skewed
      toward a Th2-type prevented graft rejection and graft-versus-host disease (GVHD)
      more potently than control Th2 cells and effectively balanced GVHD and graft
      versus-tumor (GVT) effects. A phase II clinical trial using low-intensity
      allogeneic hematopoietic cell transplantation demonstrated that interleukin-4
      polarized human T-Rapa cells had a mixed Th2/Th1 phenotype; T-Rapa cell
      recipients had a balanced Th2/Th1 cytokine profile, conversion of mixed chimerism
      toward full donor chimerism, and a potentially favorable balance between GVHD and
      GVT effects. In addition, a phase I clinical trial evaluating autologous T-Rapa
      cells skewed toward a Th1- and Tc1-type is underway. Use of ex vivo rapamycin to
      modulate effector T-cell function represents a promising new approach to
      transplantation therapy. 

PMID- 24329800
TI  - Genetically engineered donor T cells to optimize graft-versus-tumor effects
      across MHC barriers.
AB  - Hematopoietic stem cell transplantation has been used for more than 50 years to
      combat hematologic malignancies. In addition to being the first stem cell
      therapy, transplantation has provided evidence for the potent anti-tumor effects
      of T cells. Facilitating T-cell-based immunity against malignancies requires a
      careful balancing act between generating a robust response and avoiding off
      target killing of healthy tissues, which is difficult to accomplish using bulk
      donor T cells. To address these issues, several approaches have been developed,
      drawing on basic T-cell biology, to potentiate graft-versus-tumor activity while
      avoiding graft-versus-host disease. Current strategies for anti-tumor cell
      therapies include: (i) selecting optimal T cells for transfer; (ii) engineering T
      cells to possess enhanced effector functions; and (iii) generating T-cell
      precursors that complete development after adoptive transfer. In this review, we
      assess the current state of the art in T-lineage cell therapy to treat
      malignancies in the context of allogeneic hematopoietic stem cell
      transplantation.

PMID- 24329802
TI  - The use of endogenous T cells for adoptive transfer.
AB  - Adoptive T-cell therapy involves the ex vivo enrichment and expansion of tumor
      reactive T cells for infusion. As an immune-based approach, adoptive therapy has
      become an increasingly attractive modality for the treatment of patients with
      cancer due to its potential for high specificity, non-cross resistance with
      conventional therapies, and promise of long-term immunoprotection. In recent
      years, a resurgence in discoveries underlying T-cell recognition, tumor immune
      evasion, and T-cell memory and differentiation coupled with the development of
      several enabling technologies have facilitated a renewed focus in the field of
      adoptive therapy and its transition to the clinical arena as a treatment modality
      for patients with cancer. In this review, endogenous T cells derived from
      peripheral blood or tumor sites will be presented as a source of effector cells
      for adoptive therapy and strategies to isolate, manipulate, and enhance the
      function of antigen-specific T cells in vitro and to augment their in vivo
      efficacy and persistence by host immunomodulation are presented in the context of
      an ever-increasing inventory of preclinical and clinically available reagents.
      Optimizing the combination of adoptive cellular therapy and other immune-based
      and conventional approaches will herald a new generation of research and clinical
      opportunities for cancer immunotherapy. 

PMID- 24329801
TI  - Hematopoietic stem cells for cancer immunotherapy.
AB  - Hematopoietic stem cells (HSCs) provide an attractive target for immunotherapy of
      cancer and leukemia by the introduction of genes encoding T-cell receptors (TCRs)
      or chimeric antigen receptors (CARs) directed against tumor-associated antigens.
      HSCs engraft for long-term blood cell production and could provide a continuous
      source of targeted anti-cancer effector cells to sustain remissions. T cells
      produced de novo from HSCs may continuously replenish anti-tumor T cells that
      have become anergic or exhausted from ex vivo expansion or exposure to the
      intratumoral microenvironment. In addition, transgenic T cells produced in vivo
      undergo allelic exclusion, preventing co-expression of an endogenous TCR that
      could mis-pair with the introduced TCR chains and blunt activity or even cause
      off-target reactivity. CAR-engineered HSCs may produce myeloid and natural killer
      cells in addition to T cells expressing the CAR, providing broader anti-tumor
      activity that arises quickly after transplant and does not solely require de novo
      thymopoiesis. Use of TCR- or CAR-engineered HSCs would likely require
      cytoreductive conditioning to achieve long-term engraftment, and this approach
      may be used in clinical settings where autologous HSC transplant is being
      performed to add a graft-versus-tumor effect. Results of experimental and
      preclinical studies performed to date are reviewed. 

PMID- 24329804
TI  - Happy New Year 2014.

PMID- 24329805
TI  - Psychopathology for what purpose?

PMID- 24329807
TI  - The preparation of VEGFR1/CD3 bispecific antibody and its specific cytotoxicity
      against VEGFR1-positive breast cancer cells.
AB  - Bispecific antibody (BsAb) has been proved to be a very effective antitumor
      approach because of its distinctive advantages of immune-mediated cytotoxicity.
      To enhance the ability to recruit and activate T lymphocytes for tumor-specific
      killing, we constructed and prepared a recombinant human single-chain Fv
      bispecific antibody (BsAb), named VEGFR1/CD3 BsAb, targeting VEGFR1 and CD3. The
      VEGFR1/CD3 BsAb was expressed in CHO-K1 cells and purified by Ni-NTA affinity
      chromatography. The CD3 and VEGFR1-binding activity of VEGFR1/CD3 BsAb was
      confirmed by flow cytometry. T lymphocyte activation and proliferation induced by
      VEGFR1/CD3 BsAb were also demonstrated in vitro. Notably, our VEGFR1/CD3 BsAb
      presented a powerful and specific killing effect against VEGFR1-positive human
      breast cancer cell MDA-MB-231 and MDA-MB-435 through activating T lymphocyte at
      very low concentrations, indicating that it will be a valuable antibody drug for
      treatment of VEGFR1-positive cancers in the future. 

PMID- 24329803
TI  - Uncoupling T-cell expansion from effector differentiation in cell-based
      immunotherapy.
AB  - Adoptive cellular immunotherapy (ACT) is a potentially curative therapy for
      patients with advanced cancer. Eradication of tumor in mouse models and humans
      correlates with both a high dose of adoptively transferred cells and cells with a
      minimally differentiated phenotype that maintain replicative capacity and
      multipotency. We speculate that response to ACT not only requires transfer of
      cells with immediate cytolytic effector function to kill the bulk of fast-growing
      tumor but also transfer of tumor-specific cells that maintain an ability for self
      renewal and the capacity to produce a continual supply of cytolytic effector
      progeny until all malignant cells are eliminated. Current in vitro methods to
      expand cells to sufficient numbers and still maintain a minimally differentiated
      phenotype are hindered by the biological coupling of clonal expansion and
      effector differentiation. Therefore, a better understanding of the physiologic
      mechanism that couples cell expansion and differentiation in CD8(+) T cells may
      improve the efficacy of ACT. 

PMID- 24329808
TI  - Hydroxy-plastochromanol and plastoquinone-C as singlet oxygen products during
      photo-oxidative stress in Arabidopsis.
AB  - In the present study, we have shown that hydroxy-plastochromanol and
      plastoquinone-C, the hydroxy derivatives of plastochromanol and plastoquinone-9,
      respectively, are specifically formed from the parent compounds upon action of
      singlet oxygen and can be regarded as stable, specific, natural products of
      singlet oxygen action during photo-oxidative stress in vivo. The presented data
      indicate that plastoquinone-C formation dominates mainly during relatively short
      periods of high light stress where efficient production of singlet oxygen takes
      place, whereas hydroxy-plastochromanol is rather formed under conditions of long
      term, less pronounced generation of singlet oxygen. An interesting observation
      was that hydroxy-plastochromanol is formed even at very low light conditions (5
      10 MUmol photons m(-2) s(-1)), indicating that singlet oxygen is generated not
      only during high light stress but also its formation by photosystem II is
      inseparably connected with the functioning of this photosystem even at the lowest
      light intensities.

PMID- 24329809
TI  - Duration of opiate exposure as a determinant of arterial stiffness and vascular
      age in male opiate dependence: a longitudinal study.
AB  - WHAT IS KNOWN AND OBJECTIVE: Despite intriguing initial and associational
      studies, there remains little research on opiate-related arterial dysfunction and
      no longitudinal studies. As opiates act potently via P16INK4A/CDKN2A identified
      on GWAS screens, and as arterial ageing is a surrogate for organismal ageing,
      this area is of general concern. METHODS: Thirty-eight male controls compared
      with 198 opiate-dependent male patients were studied longitudinally using
      SphygmoCor pulse wave analysis. RESULTS AND DISCUSSION: Healthy male controls and
      opiate-dependent male patients were studied on 125 and 625 occasions,
      respectively. The mean (+/-SEM) chronological age (CA) was 42.32 +/- 2.22 for
      controls and 35.04 +/- 0.61 for opiate dependent (P = 0.0029). 94.4% and 13.2%
      smoked tobacco (P < 0.0001). Controlling for BMI and CA, there was a significant
      time: addictive status interaction for vascular age (P = 0.0127) and central
      augmentation pressure and index (both P < 0.02). Central systolic and diastolic
      pressures were also worse over time by addictive status (P < 0.005). At repeated
      measures multiple regression adjusted for classical risk factors, opiate dose and
      duration of opiate use remained significant. The dose-duration effect was
      significant in 8 terms and by time. A similar model quadratic in opiate duration
      was more powerfully predictive, suggesting the salience of the duration of opiate
      treatment (AIC 191.6898 and 191.5966, P = 0.0116). WHAT IS NEW AND CONCLUSION:
      Data suggest that increased length of opiate dependence is associated with
      advanced vascular stiffness and ageing and are therefore consistent with
      accelerated ageing organismally. The superiority of power functions of the opiate
      duration of exposure underscores the significance of the duration of treatment
      and of putative senescence induction.

PMID- 24329810
TI  - A systematic review of computerised serious educational games about alcohol and
      other drugs for adolescents.
AB  - ISSUES: Serious educational games (SEG) have been shown to be effective in
      educating young people about a range of topics, including languages and maths.
      This paper identifies the use of computerised SEGs in education about alcohol and
      other drugs and reviews their impact on the prevention of alcohol and drug use.
      APPROACH: The Cochrane Library, EMBASE, MEDLINE, ERIC, Scopus, psychINFO, pubMED
      and DRUG databases were searched in February 2013. Additional publications were
      obtained from the reference lists of the relevant papers. Studies were included
      if they described an evaluation of a computerised SEG that targeted alcohol
      and/or other drugs and had been trialled with adolescents. KEY FINDINGS: Eight
      SEGs were identified targeting tobacco, alcohol, cannabis, methamphetamine,
      ecstasy, inhalants, cocaine and opioids. Six reported positive outcomes in terms
      of increased content knowledge and two reported increased negative attitudes
      towards the targeted drugs. Only one reported a decrease in the frequency of drug
      use. IMPLICATIONS AND CONCLUSION: This is the first review of the efficacy of
      computerised SEGs for alcohol and other drugs for adolescents. Results suggest
      that SEGs can increase content knowledge of alcohol and other drugs. Evidence
      concerning impacts on negative attitudes and alcohol and drug use is limited,
      with few studies examining these outcomes.

PMID- 24329811
TI  - Potential energy surfaces for chemical reactions at solid surfaces.
AB  - Many-body potential energy surfaces (PESs) for describing atomic interactions in
      gas-solid and surface reaction dynamics are reviewed in this work. Initial PESs
      from the 1960s-1970s were restricted to a diatomic molecule interacting with a
      solid surface. Since the 1980s, a multitude of many-body reactive PESs, their
      parameterization, and their applications have been reported in the literature.
      Although we mention most of the PESs in general, we have chosen to describe only
      those that either have had general utility or have had staying power, i.e. they
      have been used widely by other research groups. The potentials discussed in the
      most detail are the Stillinger-Weber and Tersoff Si PESs, the Brenner hydrocarbon
      PES, and the embedded-atom method (EAM) style potentials for metals. We conclude
      that although these PESs have been used successfully in large-scale computer
      simulations, further development is needed in many-body PESs. In particular, the
      development of new functional forms for multicomponent reactive systems is
      required. 

PMID- 24329812
TI  - Wood specific gravity and anatomy of branches and roots in 113 Amazonian
      rainforest tree species across environmental gradients.
AB  - Wood specific gravity (WSG) is a strong predictor of tree performance across
      environmental gradients. Yet it remains unclear how anatomical elements linked to
      different wood functions contribute to variation in WSG in branches and roots
      across tropical forests. We examined WSG and wood anatomy in white sand, clay
      terra firme and seasonally flooded forests in French Guiana, spanning broad
      environmental gradients found throughout Amazonia. We measured 15 traits relating
      to branches and small woody roots in 113 species representing the 15 most
      abundant species in each habitat and representative species from seven
      monophyletic lineages occurring in all habitats. Fiber traits appear to be major
      determinants of WSG, independent of vessel traits, in branches and roots. Fiber
      traits and branch and root WSG increased from seasonally flooded species to clay
      terra firme species and lastly to white sand species. Branch and root wood traits
      were strongly phylogenetically constrained. Lineages differed in wood design, but
      exhibited similar variation in wood structure across habitats. We conclude that
      tropical trees can invest differently in support and transport to respond to
      environmental conditions. Wind disturbance and drought stress represent
      significant filters driving tree distribution of Amazonian forests; hence we
      suggest that biophysical explanations should receive more attention. 

PMID- 24329813
TI  - Relationship between the epithelial expression of hMLH1, MDM2, and p63 and lower
      lip carcinogenesis.
AB  - OBJECTIVES: To evaluate the relationship between the epithelial expression of
      hMLH1, MDM2, and p63 in lower lip carcinogenesis, comparing the immunostaining of
      these proteins in cases of actinic cheilitis (AC) and lower lip squamous cell
      carcinoma (SCC). STUDY DESIGN: Forty cases of AC and 40 cases of SCC were
      studied, both lesions were of lower lip. Histological sections of 3 MUm were
      submitted to immunoperoxidase method, and 1000 cells were counted for
      immunohistochemical analysis of lesions. The results were analyzed
      quantitatively, and expression was compared by the Mann-Whitney, Student t-test,
      or one-way ANOVA, adopting a level of significance of 5%. RESULTS: A higher
      percentage of epithelial cells expressing hMLH1 was observed in cases of AC
      without dysplasia or mild dysplasia (721.23 +/- 88.116), whereas fewer positive
      cells were observed in lower lip SSCs (255.03 +/- 199.47) when compared to the AC
      group (P < 0.001). Immunoexpression of MDM2 was higher in SCCs of the lower lip
      compared with AC (P = 0.019). For p63 protein, the expression was higher in AC
      than in SCC (P = 0.045). CONCLUSION: The present results showed changes in the
      immunoexpression of hMLH1, MDM2, and p63 in epithelial cells from premalignant
      and malignant lip disease, supporting the hypothesis that these alterations are
      related to the process of lower lip carcinogenesis.

PMID- 24329814
TI  - Determining the effect of immunosuppressant adherence on graft failure risk among
      renal transplant recipients.
AB  - The objective was to use the United States Renal Data System (USRDS) to quantify
      the relationship between immunosuppressant therapy (IST) adherence and risk of
      graft failure among adult renal transplant recipients (RTRs). A secondary
      objective was to examine the relationship among select patient characteristics
      and IST adherence. The study sample included adult RTRs who: received primary
      transplant between January 1, 1999 and December 31, 2005; experienced graft
      survival for at least 12 months post-transplant and had at least 12 months of
      data in the USRDS; utilized Medicare coverage for IST; and were prescribed
      cyclosporine or tacrolimus. IST adherence was measured by medication possession
      ratio (MPR). Pearson chi-square tests were used to examine associations between
      patient characteristics and MPR quartiles. Cox proportional hazards regression
      was used to assess relationships among time to graft failure, MPR, and patient
      characteristics. Thirty-one thousand nine hundred and thirteen RTRs met inclusion
      criteria. Older age, female gender, white race, deceased donors, and tacrolimus
      were associated with greater adherence (p < 0.001). Cox proportional hazard
      modeling indicated greater adherence, white race, and having a living donor were
      significantly associated with longer graft survival (p < 0.05). Future
      prospective studies should further examine the clinical significance of IST
      nonadherence as it relates to graft failure. 

PMID- 24329815
TI  - Meningothelial hamartoma associated with nevus sebaceus.
AB  - Meningothelial hamartoma is a rare lesion of ectopic meningothelial elements that
      usually presents on the scalp at birth or in early childhood. The characteristic
      spindle cells infiltrate through collagen and stain positively for epithelial
      membrane antigen and vimentin but are negative for CD31 and CD34. This
      distinguishes meningothelial hamartoma from vascular tumors. Nevus sebaceus is a
      fairly common lesion that has been associated with several different benign
      tumors, including trichoblastoma and syringocystadenoma papilliferum. We describe
      the case of a 17-month-old girl who presented with a meningothelial hamartoma in
      association with a nevus sebaceus. To the best of our knowledge, this is the
      second case reported. 

PMID- 24329816
TI  - The quantitative analysis of spreadability, coverage, and adhesion effect after
      application of the base make-up product.
AB  - BACKGROUND/PURPOSE: It is needed to evaluate the spreadability, coverage, and
      adhesion of facial base makeup products. METHODS: Using the oscillation
      applicator or hand application, 20 volunteers spread the liquid foundation on
      their faces and forearms. To assess the spreadability, coverage, and adhesion, we
      analyzed digital images of volunteers' faces to measure spreadability and
      coverage, and we measured the adhesion effect on the forearm by tape-stripping.
      RESULTS: In terms of spreadability, coverage, and adhesion, the results of group
      who used the 'oscillation applicator' were significantly twice as high as the
      other group who applied by hand. CONCLUSION: In this study, we demonstrated a
      method for quantitative assessing the effect of spreadability, coverage, and
      adhesion of the liquid foundation used in base makeup. Also, we discovered a
      distinction between using an oscillation applicator and using hand application.
      It is expected that image analysis assessment and tape-stripping would be useful
      parameters for the evaluation of the facial base makeup.

PMID- 24329817
TI  - Cytosolic APX knockdown rice plants sustain photosynthesis by regulation of
      protein expression related to photochemistry, Calvin cycle and photorespiration.
AB  - The biochemical mechanisms underlying the involvement of cytosolic ascorbate
      peroxidases (cAPXs) in photosynthesis are still unknown. In this study, rice
      plants doubly silenced in these genes (APX1/2) were exposed to moderate light
      (ML) and high light (HL) to assess the role of cAPXs in photosynthetic
      efficiency. APX1/2 mutants that were exposed to ML overexpressed seven and five
      proteins involved in photochemical activity and photorespiration, respectively.
      These plants also increased the pheophytin and chlorophyll levels, but the amount
      of five proteins that are important for Calvin cycle did not change. These
      responses in mutants were associated with Rubisco carboxylation rate, photosystem
      II (PSII) activity and potential photosynthesis, which were similar to non
      transformed plants. The upregulation of photochemical proteins may be part of a
      compensatory mechanism for APX1/2 deficiency but apparently the finer-control for
      photosynthesis efficiency is dependent on Calvin cycle proteins. Conversely,
      under HL the mutants employed a different strategy, triggering downregulation of
      proteins related to photochemical activity, Calvin cycle and decreasing the
      levels of photosynthetic pigments. These changes were associated to strong
      impairment in PSII activity and Rubisco carboxylation. The upregulation of some
      photorespiratory proteins was maintained under that stressful condition and this
      response may have contributed to photoprotection in rice plants deficient in
      cAPXs. The data reveal that the two cAPXs are not essential for photosynthesis in
      rice or, alternatively, the deficient plants are able to trigger compensatory
      mechanisms to photosynthetic acclimation under ML and HL conditions. These
      mechanisms involve differential regulation in protein expression related to
      photochemistry, Calvin cycle and photorespiration. 

PMID- 24329818
TI  - Mother-reported sleep, accelerometer-estimated sleep and weight status in Mexican
      American children: sleep duration is associated with increased adiposity and risk
      for overweight/obese status.
AB  - We know of no studies comparing parent-reported sleep with accelerometer
      estimated sleep in their relation to paediatric adiposity. We examined: (i) the
      reliability of mother-reported sleep compared with accelerometer-estimated sleep;
      and (ii) the relationship between both sleep measures and child adiposity. The
      current cross-sectional study included 303 Mexican American mother-child pairs
      recruited from Kaiser Permanente Northern California. We measured sleep duration
      using maternal report and accelerometry and child anthropometrics. Concordance
      between sleep measures was evaluated using the Bland-Altman method. We conducted
      zero-ordered correlations between mother-reported sleep, accelerometer-estimated
      sleep and child BMI z-scores (BMIz). Using linear regression, we examined three
      models to assess child BMIz with mother-reported sleep (model 1), accelerometer
      estimated sleep (model 2) and both sleep measures (model 3). Children had an
      average age of 8.86 years (SD = 0.82). Mothers reported that their child slept
      9.81 +/- 0.74 h [95% confidence interval (CI): 9.72, 9.89], compared to 9.58 +/-
      0.71 h (95% CI: 9.50, 9.66) based on accelerometry. Mother-reported sleep and
      accelerometer-estimated sleep were correlated (r = 0.33, P < 0.001). BMIz
      outcomes were associated negatively with mother-reported sleep duration (model 1:
      beta = -0.13; P = 0.02) and accelerometer-estimated sleep duration (model 2: beta
      = -0.17; P < 0.01). Accounting for both sleep measures, only accelerometer
      measured sleep was related to BMIz (model 3: beta = -0.14, P = 0.02). Each sleep
      measure was related significantly to adiposity, independent of covariates.
      Accelerometry appeared to be a more reliable measure of children's sleep than
      maternal report, yet maternal report may be sufficient to examine the sleep
      adiposity relationship when resources are limited. 

PMID- 24329819
TI  - The mediating effect of chronic pain on the relationship between obesity and
      physical function and disability in older adults.
AB  - OBJECTIVES: To determine the extent to which bodily pain mediates the effect of
      obesity on disability and physical function. DESIGN: Cross-sectional analysis.
      SETTING: Population-based sample of residents in the greater Boston area.
      PARTICIPANTS: Community-dwelling adults aged 70 and older (N=736). MEASUREMENTS:
      Body mass index (BMI), obtained from measured height and weight, was categorized
      as normal weight (19.0-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese
      (>=30.0 kg/m2). Main outcome measures were the Physical Component Summary of the
      Medical Outcomes Study 12-item Short-Form Survey (PCS), activity of daily living
      (ADL) disability, and Short Physical Performance Battery (SPPB) score. Chronic
      pain was assessed according to the number of weight-bearing joint sites that had
      pain (hips, knees, feet and pain all over). RESULTS: Older obese adults had
      greater ADL disability and lower SPPB and PCS scores than their nonobese
      counterparts, although in sex-stratified adjusted analyses, obesity was adversely
      associated with outcomes only in women. Obesity was associated with greater
      number of pain sites; and more pain sites were associated with greater odds of
      disability. Mediation analysis suggests that pain is a significant mediator (22
      44%) of the adverse effect of obesity on disability and physical function in
      women. CONCLUSION: Bodily pain may be an important treatable mediator of the
      adverse effect of obesity on disability and physical function in women.

PMID- 24329820
TI  - Use of International Classification of Diseases, Ninth Revision, Clinical
      Modification, codes to identify inpatient fall-related injuries.
AB  - OBJECTIVES: To compare falls and fall-related injuries that a fall evaluator or
      hospital incident report identified with injuries identified according to
      discharge International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM) codes for the same set of inpatient episodes of care.
      DESIGN: Prospective, descriptive study. SETTING: Sixteen adult general medical
      and surgical units in a major urban teaching hospital. PARTICIPANTS: All adults
      who sustained a fall with injury during a 5-year period (380 falls with injury).
      MEASUREMENTS: Falls that a fall evaluator or hospital incident report identified
      were classified according to their injury severity. Discharge abstracts provided
      diagnosis codes (ICD-9-CM) for the discharge, including fall-related injury
      codes. RESULTS: Three hundred forty-three inpatient falls with injury (90.2%)
      resulted in temporary harm to the individual; the remaining 37 falls (9.8%)
      resulted in more-serious harm. Sixteen of the 37 falls with injury extending
      hospitalization or resulting in death were identified using Centers for Medicare
      and Medicaid Services (CMS)-targeted injury code ranges combined with present-on
      admission indicators. Of the 21 falls with injury that were not identified, nine
      (42.9%) lacked documentation of any injury, and seven (33.3%) identified other
      injuries outside the CMS-targeted injury code ranges. CONCLUSION: The CMS
      targeted ICD-9-CM codes used to identify fall-related injuries in claims data do
      not always detect the most-serious falls.

PMID- 24329821
TI  - The University of California at Los Angeles Alzheimer's and Dementia Care program
      for comprehensive, coordinated, patient-centered care: preliminary data.
AB  - Dementia is a chronic disease that requires medical and social services to
      provide high-quality care and prevent complications. As a result of time
      constraints in practice, lack of systems-based approaches, and poor integration
      of community-based organizations (CBOs), the quality of care for dementia is
      poorer than that for other diseases that affect older persons. The University of
      California at Los Angeles (UCLA) Alzheimer's and Dementia Care (UCLA ADC) program
      partners with CBOs to provide comprehensive, coordinated, patient-centered care
      for individuals with Alzheimer's disease and other dementias. The goals of the
      program are to maximize function, independence, and dignity; minimize caregiver
      strain and burnout; and reduce unnecessary costs. The UCLA ADC program consists
      of five core components: recruitment and a dementia registry, structured needs
      assessments of individuals in the registry and their caregivers, creation and
      implementation of individualized dementia care plans based on needs assessments
      and input from the primary care physicians, monitoring and revising care plans as
      needed, and around-the-clock access for assistance and advice. The program uses a
      comanagement model with a nurse practitioner Dementia Care Manager working with
      primary care physicians and CBOs. Based on the first 150 individuals served, the
      most common recommendations in the initial care plans were referrals to support
      groups (73%) and Alzheimer's Association Safe Return (73%), caregiver training
      (45%), and medication adjustment (41%). The program will be evaluated on its
      ability to achieve the triple aim of better care for individuals, better health
      for populations, and lower costs. 

PMID- 24329822
TI  - High troponin levels after noncardiac surgery: cause for concern?

PMID- 24329823
TI  - Outbreak of respiratory syncytial virus infections in a nursing home and possible
      sources of introduction: the Netherlands, winter 2012/2013.

PMID- 24329824
TI  - Comparison of stair descent and ramp descent during performance of cognitive
      secondary task in elderly community-dwelling adults.

PMID- 24329825
TI  - Body mass index, health status, and mortality of older Taiwanese men: overweight
      good, underweight bad, obesity neutral.

PMID- 24329826
TI  - Weight loss and homeostatic imbalance of leptin and ghrelin levels in lean older
      adults.

PMID- 24329827
TI  - Are geriatric syndromes associated with reluctance to initiate oral
      anticoagulation therapy in elderly adults with nonvalvular atrial fibrillation?

PMID- 24329828
TI  - Normal respiratory rate and peripheral blood oxygen saturation in the elderly
      population.

PMID- 24329829
TI  - Purple urine-bag syndrome in a department of medicine.

PMID- 24329830
TI  - Relationship between depression and blood pressure in community-dwelling oldest
      old adults in Japan.

PMID- 24329831
TI  - Effect and sustainability of pharmacy outreach services in elderly adults: a 5
      year experience in Hong Kong.

PMID- 24329832
TI  - Comparison of methods to measure height in older adults.

PMID- 24329834
TI  - In-hospital hip fracture mortality trends in older adults: the National Hospital
      Discharge Survey, 1988-2007.

PMID- 24329833
TI  - Regional white matter hyperintensity volume and cognition predict death in a
      multiethnic community cohort of older adults.

PMID- 24329835
TI  - Functional outcomes in elderly adults who have undergone major colorectal
      surgery.

PMID- 24329836
TI  - Living arrangements are not associated with length of hospital stay.

PMID- 24329837
TI  - Effect of cognitive training targeting associative memory in the elderly: a small
      randomized trial and a longitudinal evaluation.

PMID- 24329838
TI  - Myopathy after switching from brand to generic atorvastatin.

PMID- 24329839
TI  - Unusual case of extensive warfarin-induced necrosis in an 84-year-old.

PMID- 24329840
TI  - Metformin-associated lactic acidosis in an older adult after colonoscopy: an
      uncommon trigger for a rare complication.

PMID- 24329841
TI  - Spontaneous quadriceps hematoma in an elderly adult taking therapeutic doses of
      warfarin.

PMID- 24329842
TI  - Changes in the clinical manifestation of fibromyalgia in an individual with
      dementia.

PMID- 24329843
TI  - Ruptured abdominal aortic aneurysm in an elderly man.

PMID- 24329844
TI  - Future of geriatric medicine in the United States: to be or not to be? A
      viewpoint on reforming geriatrics.

PMID- 24329845
TI  - Structural violence on elderly people's oral health.

PMID- 24329846
TI  - The ethical intersection of elder law and elder care practices.

PMID- 24329847
TI  - Medicare and the 3-day rule.

PMID- 24329848
TI  - Uric acid for prediction of cardiovascular mortality in older adults.

PMID- 24329849
TI  - Response letter to Shil and colleagues.

PMID- 24329850
TI  - Effect of metronidazole versus standard care on length of stay of patients
      admitted with severe infectious mononucleosis: a randomized controlled trial.
AB  - Metronidazole may be of use in the treatment of infectious mononucleosis (IM).
      Our aim is to show that metronidazole shortens hospital stay for patients with
      severe IM. A single-centre randomized controlled trial was undertaken in patients
      admitted with severe IM, who were with a similar group treated by the standard
      care. Patients were blinded to which treatment arm they were in. Forty-two of
      these patients were enrolled in the trial. The primary endpoint was the
      difference in length of stay. This was significantly less in the metronidazole
      group (3.67 days v 4.67) (p 0.032). This study demonstrates that metronidazole
      has a role to play in severe infectious mononucleosis.

PMID- 24329851
TI  - Targeted mutagenesis of multiple and paralogous genes in Xenopus laevis using two
      pairs of transcription activator-like effector nucleases.
AB  - Transcription activator-like effector nucleases (TALENs) have been extensively
      used in genome editing in various organisms. In some cases, however, it is
      difficult to efficiently disrupt both paralogous genes using a single pair of
      TALENs in Xenopus laevis because of its polyploidy. Here, we report targeted
      mutagenesis of multiple and paralogous genes using two pairs of TALENs in X.
      laevis. First, we show simultaneous targeted mutagenesis of three genes,
      tyrosinase paralogues (tyra and tyrb) and enhanced green fluorescent protein
      (egfp) by injection of two TALENs pairs in transgenic embryos carrying egfp.
      Consistent with the high frequency of both severe phenotypic traits, albinism and
      loss of GFP fluorescence, frameshift mutation rates of tyr paralogues and egfp
      reached 40-80%. Next, we show early introduction of TALEN-mediated mutagenesis of
      these target loci during embryogenesis. Finally, we also demonstrate that two
      different pairs of TALENs can simultaneously introduce mutations to both
      paralogues encoding histone chaperone with high efficiency. Our results suggest
      that targeted mutagenesis of multiple genes using TALENs can be applied to
      analyze the functions of paralogous genes with redundancy in X. laevis. 

PMID- 24329852
TI  - Hepatitis C and lipid metabolism, hepatic steatosis, and NAFLD: still important
      in the era of direct acting antiviral therapy?
AB  - Chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) have an
      individual prevalence of 1.8-3% and at least 30%, respectively, in the United
      States. It is therefore not surprising that there is overlap between these two
      common chronic liver diseases, although the relationship appears to go beyond
      isolated co-existence. Hepatic steatosis is a common feature of CHC infection and
      can be related to both metabolic and viral specific factors. Steatosis in the
      setting of nongenotype 3 CHC has been predictive of response to therapy prior to
      the advent of the direct acting antiviral medications (DAAs). Similarly, lipid
      metabolism appears important in response to CHC treatment. The pathways for both
      lipid homeostasis and NAFLD as it pertains to CHC infection as well as the
      utilization of statin therapy in CHC infection will be reviewed with a focus on
      the relevance of these topics in the era of DAA therapy. 

PMID- 24329853
TI  - Hepatitis C virus dysregulates glucose homeostasis by a dual mechanism involving
      induction of PGC1alpha and dephosphorylation of FoxO1.
AB  - The maintenance of glucose homeostasis is a complex process in which the insulin
      signalling pathway plays a major role. Disruption of insulin-regulated glucose
      homeostasis is frequently observed in chronic hepatitis C (CHC) infection and
      might potentially contribute to type 2 diabetes mellitus (T2DM) development.
      Presently, the mechanism that links HCV infection to insulin resistance remains
      unclear. Previously, we have reported that HCV protein expression in HCV
      transgenic mice (B6HCV) leads to an overexpression of protein phosphatase 2A
      (PP2A) through an ER stress response. In the present work, we describe an
      association of FoxO1 hypophosphorylation and upregulation of both PGC-1alpha and
      G6Pase to phenotypic hyperglycaemia and insulin resistance in B6HCV mice. In
      vitro, we observed that PGC1alpha is concomitantly induced with PP2A. Moreover,
      we show that the enhanced PP2A expression is sufficient to inhibit insulin
      induced FoxO1 phosphorylation via blockade of insulin-mediated Akt activation
      or/and through direct association and dephosphorylation of pS-FoxO1.
      Consequently, we found that the gluconeogenic gene glucose-6-phosphatase is
      upregulated. These observations were confirmed in liver biopsies obtained from
      CHC patients. In summary, our results show that HCV-mediated upregulation of PP2A
      catalytic subunit alters signalling pathways that control hepatic glucose
      homeostasis by inhibiting Akt and dephosphorylation of FoxO1. 

PMID- 24329854
TI  - Risk of transmission associated with sharing drug injecting paraphernalia:
      analysis of recent hepatitis C virus (HCV) infection using cross-sectional survey
      data.
AB  - Sharing injecting paraphernalia (containers, filters and water) poses a risk of
      transmitting the hepatitis C virus (HCV). The prevalence of, and risk of HCV
      from, such behaviour has not been extensively reported in Europe. People who
      inject drugs (PWID) were recruited in cross-sectional surveys from services
      providing sterile injecting equipment across Scotland between 2008 and 2010.
      Participants completed a questionnaire and provided a blood spot for anonymous
      testing. Logistic regression was used to examine the association between recent
      HCV infection (anti-HCV negative and HCV-RNA positive) and self-reported measures
      of injecting equipment sharing in the 6 months preceding interview. Twelve per
      cent of the sample reported sharing needles/syringes, and 40% reported sharing
      paraphernalia in the previous 6 months. The adjusted odds ratios (AOR) for
      sharing needles/syringes (+/- paraphernalia), and sharing only paraphernalia in
      the last 6 months were 6.7 (95% CI 2.6-17.1) and 3.0 (95% CI 1.2-7.5),
      respectively. Among those who reported not sharing needles/syringes, sharing
      containers and filters were both significantly associated with recent HCV
      infection (AOR 3.1, 95% CI 1.3-7.8 and 3.1, 95% CI 1.3-7.5, respectively);
      sharing water was not. We present the first study to apply a cross-sectional
      approach to the analysis of the association between sharing paraphernalia and
      incident HCV infection and demonstrate consistent results with previous
      longitudinal studies. The prevalence of paraphernalia sharing in our study
      population is high, representing significant potential for HCV transmission. 

PMID- 24329855
TI  - Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV-/HCV
      coinfected patients: the role of metabolic factors and elevated GGT levels.
AB  - Evaluation of metabolic factors and elevated gamma-glutamyltransferase (GGT)
      levels as independent predictors of treatment failure in a thoroughly documented
      cohort of HIV-/HCV-coinfected patients (HIV/HCV). Sixty-four HIV/HCV patients
      treated with pegylated interferon-alpha-2a plus ribavirin (PEGIFN + RBV) at the
      Medical University of Vienna within a prospective trial were included in this
      study. In addition, 124 patients with HIV/HCV from the AIFA-HIV and AHIVCOS
      cohorts were included as a validation cohort. Advanced liver fibrosis, GGT
      elevation, insulin resistance (IR) and low CD4+ nadir were defined as METAVIR
      F3/F4, GGT levels >1.5* sex-specific upper limit of normal, homoeostasis model
      assessment of insulin resistance >2 and CD4+ nadir <350 cells/MUL, respectively.
      HCV-genotype 1/4 (OR26.3; P = 0.006), advanced liver fibrosis (OR20.2; P =
      0.009), interleukin 28B rs12979860 non-C/C SNP (OR8.27; P = 0.02) and GGT
      elevation (OR7.97; P = 0.012) were independent predictors of treatment failure,
      while both IR (OR3.51; P = 0.106) and low CD4 + nadir (OR2.64; P = 0.263) were
      not independently associated with treatment failure. A statistically significant
      correlation between GGT elevation and prior alcohol abuse (r = 0.259; P = 0.039),
      liver steatosis (r = 0.301; P = 0.034) and low-density lipoprotein-cholesterol (r
      = -0.256; P = 0.041) was observed. The importance of GGT elevation as an
      independent predictor of treatment failure was confirmed in a validation cohort
      (OR2.76; P = 0.026). While GGT elevation emerged as an independent predictor of
      treatment failure in both the derivation and the validation cohort, no
      independent associations between metabolic factors and treatment failure were
      observed. Thus, our findings suggest that GGT elevation is an independent
      predictor of treatment failure in HIV/HCV that can easily be incorporated into
      predictive algorithms. 

PMID- 24329856
TI  - Impact of ribavirin priming on viral kinetics and treatment response in chronic
      hepatitis C genotype 1 infection.
AB  - Ribavirin amplifies the interferon-alpha (IFN) signalling cascade. As ribavirin
      needs 4 weeks to reach steady state, ribavirin priming may optimize hepatic IFN
      sensitivity before starting a pegylated (PEG)-IFN/ribavirin combination therapy.
      This study investigated potential benefits of ribavirin priming prior to PEG
      IFN2a/ribavirin combination therapy on viral kinetics, on-treatment and sustained
      virological response (SVR) in chronic hepatitis C virus (HCV) genotype 1
      infection. Sixty-eight treatment naive patients were randomized 2:2:1 to
      ribavirin (ribavirin arm) or placebo (placebo arm) or PEG-IFN2a (PEG-IFN2a arm)
      for 6 weeks prior to 12 weeks of PEG-IFN2a/ribavirin combination therapy within a
      double-blind, placebo-controlled trial. Then, standard PEG-IFN2a/ribavirin
      combination therapy according to the German guidelines was continued under the
      responsibility of the investigators. Ribavirin was given according to body weight
      and PEG-IFN2a at a dose of 180 MUg subcutaneously once/week. During ribavirin
      priming, HCV RNA showed a decline of -0.58 log10  IU/mL (P < 0.001) that was
      unrelated to the IL28B rs12979860 genotype (CC vs CT/TT, P = 0.244). Ribavirin
      priming did neither increase the PEG-IFN2a-induced first- or second-phase viral
      decline (P values >0.100) nor on-treatment response or SVR (HCV RNA undetectable
      at week 12 of combination therapy: ribavirin arm 56%, placebo arm 38%, PEG-IFN2a
      arm 50%; SVR: ribavirin arm 41%, placebo arm 54%, PEG-IFN2a arm 50%; P values
      >0.300). In conclusion, ribavirin monotherapy showed a significant antiviral
      activity that was not influenced by the IL28B genotype. Ribavirin priming prior
      to PEG-IFN2a/ribavirin combination therapy did neither increase the first- or
      second-phase viral decline nor on-treatment response or SVR. 

PMID- 24329857
TI  - Cross-sectional and dynamic change of serum metabolite profiling for Hepatitis B
      related acute-on-chronic liver failure by UPLC/MS.
AB  - Summary Acute-on-chronic liver failure(ACLF) is an increasingly recognized entity
      encompassing an acute deterioration of liver function and results in the failure
      of one or more organs with high short-term mortality. The focus of this study was
      to discover noninvasive and reliable biomarkers for the diagnosis and prognosis
      of hepatitis B-related ACLF. Ultra-performance liquid chromatography-mass
      spectrometry (UPLC/MS) was used to analyse serum metabolites of 28 patients with
      hepatitis B-related ACLF, 35 patients with Child-Pugh A cirrhosis, 30 patients
      with chronic hepatitis B and 35 healthy volunteers (HS). Characteristic
      metabolites were screened, identified and dynamically tracked to investigate
      their value for diagnosis and prognosis. After comparing serum metabolic profile
      of hepatitis B-related ACLF and Child-Pugh A cirrhosis, 99 characteristic
      metabolites were selected, and 38 of them were identified. Dynamic tracking model
      demonstrated that 17 metabolites were related to prognosis of hepatitis B-related
      ACLF, and there were also 11 metabolites which improved with treatment in the
      survival group. The correlations between these characteristic metabolites and the
      model for end-stage liver disease score were strong. These observations
      contributed to the investigation of the mechanisms of hepatitis B-related ACLF
      manifestation and progression on the metabolic level, and they provided
      information for the identification of biomarkers for the diagnosis and prognosis
      of hepatitis B-related ACLF. 

PMID- 24329858
TI  - Elevated expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8)
      like 2 mRNA in peripheral blood mononuclear cells is associated with disease
      progression of acute-on-chronic hepatitis B liver failure.
AB  - Aberrant immunity response contributes to the pathogenesis of acute-on-chronic
      hepatitis B liver failure. Tumour necrosis factor-alpha-induced protein-8 like-2
      (TIPE2) is a recently identified molecular to maintain immune homoeostasis, but
      its role in acute-on-chronic hepatitis B liver failure (ACHBLF) is unknown. We
      detected TIPE2 mRNA levels in peripheral blood mononuclear cells (PBMCs) from 56
      patients with ACHBLF, 60 chronic hepatitis B patients, 24 healthy controls and
      analysed its role in disease severity and prognosis. TIPE2 mRNA expression in
      patients with ACHBLF was higher than that of patients with chronic infection or
      healthy controls. In patients with ACHBLF, TIPE2 mRNA level was positively
      correlated with serum total bilirubin, international normalized ratio and model
      for end-stage liver disease scores. Furthermore, the level of TIPE2 mRNA was
      significantly higher in nonsurvivors than survivors in patients with ACHBLF. The
      mRNA level of TIPE2 gradually decreased week by week in survivors accompanied by
      recovery from patients with ACHBLF, while its expression sustained at high levels
      in nonsurvivors. TIPE2 mRNA level after lipopolysaccharide (LPS) stimulation ex
      vivo in patients with ACHBLF was higher compared with controls and patients with
      chronic infection. Meanwhile, cytokines ex vivo secreted were measured as a
      marker of immune activation. After LPS stimulation, interleukin (IL)-6 and tumour
      necrosis factor (TNF)-alpha mRNA expression were reduced in patients with ACHBLF,
      and a significantly negative correlation was found between TIPE2 and TNF-alpha
      mRNA levels. In conclusion, our results identified the potential role of TIPE2 in
      predicting disease progression and prognosis in patients with ACHBLF by negative
      regulating of cell-mediated immunity. 

PMID- 24329859
TI  - Cascading effects of predator-detritivore interactions depend on environmental
      context in a Tibetan alpine meadow.
AB  - Studies of grazing food webs show that species traits can interact with
      environmental factors to determine the strength of trophic cascades, but
      analogous context dependencies in detrital food webs remain poorly understood. In
      predator-detritivore-plant interaction chains, predators are expected to
      indirectly suppress plant biomass by reducing the density of plant-facilitating
      detritivores. However, this outcome can be reversed where above-ground predators
      drive burrowing detritivores to lower soil levels, strengthening their plant
      facilitating effects. Here, we show that these trait-mediated indirect
      interactions further depend on environmental context in a Tibetan alpine meadow.
      In our study system, undulating topography generates higher (dry soil) patches
      interspersed with lower (wet soil) patches. Because the ability of detritivores
      to form deep burrows is likely to be limited by oxygen availability in low
      patches (wet soil), we hypothesized that (i) burrowing detritivores would undergo
      a vertical habitat shift, allowing them to more effectively avoid predation, in
      high - but not low - patches, and (ii) this shift would transmit positive effects
      of predators to plants in high patches by improving conditions in the lower soil
      layer. We tested these hypotheses using complementary field and glasshouse
      experiments examining whether the cascading effects of above-ground predatory
      beetles (presence/absence) on the density and behaviour of tunnel-forming
      detritivorous beetles, soil properties, and plant growth varied with patch type
      (low/high). Results revealed that predatory beetles did not reduce the density of
      detritivores in either patch type but had context-dependent trait-mediated
      effects, increasing the tunnelling depth of detritivores, improving soil
      conditions and ultimately increasing plant biomass in the high but not low
      patches. This study adds to an emerging predictive framework linking predators to
      plants in detritus food webs, demonstrating that these indirect interactions
      depend not just on the relative habitat domains of predators and prey, but also
      on environmental conditions that can predictably constrain the behavioural
      response of detritivores to predation risk. 

PMID- 24329860
TI  - Efficient production of fermentable sugars from oil palm empty fruit bunch by
      combined use of acid and whole cell culture-catalyzed hydrolyses.
AB  - Empty fruit bunch (EFB) of oil palm trees was converted to fermentable sugars by
      the combined use of dilute acids and whole fungal cell culture-catalyzed
      hydrolyses. EFB (5%, w/v) was hydrolyzed in the presence of 0.5% H2 SO4 and 0.2%
      H3 PO4 at 160  degrees C for 10 Min. The solid fraction was separated from the
      acid hydrolysate by filtration and subjected to enzymatic hydrolysis at 50 
      degrees C using the whole cell culture of Trichoderma reesei RUT-C30 (2%, w/v),
      which was prepared by cultivation at 30  degrees C for 7 days to reach its
      maximal cellulase activity. The combined hydrolyses of EFB gave a total sugar
      yield of 82.0%. When used as carbon sources for cultivating Escherichia coli in
      M9 medium at 37  degrees C, the combined EFB hydrolysates were shown to be more
      favorable or at least as good as pure glucose for cell growth in terms of the
      higher (1.1 times) optical density of E. coli cells. The by-products generated
      during the acid-catalyzed hydrolysis did not seem to obviously affect cell
      growth. The combined use of acid and whole cell culture hydrolyses might be a
      commercially promising method for pretreatment of lignocellulose to get
      fermentable sugars. 

PMID- 24329861
TI  - Epicutaneous immune modulation with Bet v 1 plus R848 suppresses allergic asthma
      in a murine model.
AB  - BACKGROUND: Combining allergen(s) with an adjuvant is a strategy to improve the
      efficacy and safety of allergen-specific immunotherapy. Here, we aimed at
      investigating the adjuvant effects of polyadenylic-polyuridylic acid (poly(A:U)),
      a TLR3 agonist, and R848 (resiquimod), a TLR7 agonist, in epicutaneous
      immunotherapy with Bet v 1, the major birch pollen allergen, to intervene in
      birch pollen allergy. METHODS AND RESULTS: BALB/c mice received epicutaneous
      immunization (EPI) with recombinant Bet v 1 (rBet v 1) alone, or plus poly(A:U),
      or R848 on their depilated back using patches. Among the groups, EPI with rBet v
      1 and R848 induced detectable levels of IFN-gamma-producing CD4(+) T cells in
      lymph nodes and Bet v 1-specific IgG2a antibodies in the sera of mice. Before or
      after EPI, mice were sensitized with rBet v 1 plus aluminium hydroxide adjuvant
      and intranasally challenged with birch pollen extract. Prophylactic EPI with rBet
      v 1 plus R848 inhibited the production of biologically active Bet v 1-specific
      IgE antibodies in sensitization. Prophylactic and therapeutic EPI with rBet v 1
      plus R848 suppressed lung inflammation upon challenges. Remarkably, only rBet v 1
      plus R848 reduced the development of enhanced pause (PenH), a substituted
      parameter for airway hyper-reactivity, in challenged mice. In contrast to R848,
      poly(A:U) did not present adjuvant effect on the suppression of asthmatic
      features. CONCLUSION: Epicutaneous immunization with rBet v 1 plus R848 induced
      predominant Bet v 1-specific Th1 responses and efficiently suppressed asthmatic
      features elicited by birch pollen. R848 could be a promising adjuvant in
      epicutaneous immunotherapy for birch pollen-induced allergic asthma.

PMID- 24329863
TI  - Genome-wide DNA profiling identifies clonal heterogeneity in marginal zone
      lymphomas.

PMID- 24329864
TI  - Algebraic methods in spectroscopy.
AB  - At present, two main types of algebraic methods are employed for analysis of
      molecular spectra. The first goes back to the early days of molecular
      spectroscopy. The second, developed recently by Iachello and coworkers, grew out
      of nuclear physics and makes use of classical Lie algebras such as SU(4). In this
      review, the standard spectroscopic fitting Hamiltonian for molecular vibrations,
      including resonance interactions, is first described. Then, new developments in
      the application of the standard approach are surveyed. In particular, the
      question of how one determines the true nature of molecular motions in highly
      excited spectra is investigated. Next, the recent algebraic approach of Iachello
      and coworkers is discussed. Application of ideas of molecule-like modes and
      algebraic methods to the analysis of the electronic spectra of atoms is
      discussed. Finally, prospects for future development of algebraic methods are
      discussed. 

PMID- 24329862
TI  - Region-specific impairments in striatal synaptic transmission and impaired
      instrumental learning in a mouse model of Angelman syndrome.
AB  - Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental
      retardation and impaired speech. Because patients with this disorder often
      exhibit motor tremor and stereotypical behaviors, which are associated with basal
      ganglia pathology, we hypothesized that AS is accompanied by abnormal functioning
      of the striatum, the input nucleus of the basal ganglia. Using mutant mice with
      maternal deficiency of AS E6-AP ubiquitin protein ligase Ube3a (Ube3a(m-/p+) ),
      we assessed the effects of Ube3a deficiency on instrumental conditioning, a
      striatum-dependent task. We used whole-cell patch-clamp recording to measure
      glutamatergic transmission in the dorsomedial striatum (DMS) and dorsolateral
      striatum (DLS). Ube3a(m-/p+) mice were severely impaired in initial acquisition
      of lever pressing. Whereas the lever pressing of wild-type controls was reduced
      by outcome devaluation and instrumental contingency reversal, the performance of
      Ube3a(m-/p+) mice were more habitual, impervious to changes in outcome value and
      action-outcome contingency. In the DMS, but not the DLS, Ube3a(m-/p+) mice showed
      reduced amplitude and frequency of miniature excitatory postsynaptic currents.
      These results show for the first time a selective deficit in instrumental
      conditioning in the Ube3a deficient mouse model, and suggest a specific
      impairment in glutmatergic transmission in the associative corticostriatal
      circuit in AS. 

PMID- 24329865
TI  - Genetic selection for resistance to mycoplasmal pneumonia of swine (MPS) in the
      Landrace line influences the expression of soluble factors in blood after MPS
      vaccine sensitization.
AB  - We recently developed a Landrace line that is resistant to mycoplasmal pneumonia
      of swine (MPS) infection by genetic selection for five generations, and we
      reported that the immunophenotype of this line is different from that of the non
      selected line in terms of changes in peripheral blood leukocyte population after
      MPS vaccination. This study followed up previous findings demonstrating changes
      in soluble factors in blood, namely, hormones, Mycoplasma hyopneumoniae-specific
      immunoglobulin G (IgG), and cytokines. These two lines were injected with MPS
      vaccine on days -7 and 0 after blood sampling on those days, and blood samples
      were collected on days -14, -7, 0, 2, 7 and 14. We found changes in the levels of
      many hormones and cytokines in both lines. However, we found that only growth
      hormone (GH) and interferon (IFN)-gamma levels were statistically different
      between these two lines. GH concentration was reduced (day 0) and IFN-gamma
      concentration was increased (day 14) in the MPS-selected line compared with the
      non-selected line, despite unchanged IFN-gamma messenger RNA expression in blood
      cells. Although detailed mechanisms underlying these phenotypes remain unsolved,
      these traits would be useful to improve MPS resistance in pig production and
      provide an insight into MPS infection. 

PMID- 24329866
TI  - Let conscience be their guide? Conscientious refusals in health care.

PMID- 24329867
TI  - Does enamel matrix derivative application provide additional clinical benefits in
      residual periodontal pockets associated with suprabony defects? A systematic
      review and meta-analysis of randomized clinical trials.
AB  - OBJECTIVE: To review the effectiveness of enamel matrix derivative (EMD) in the
      treatment of periodontal pockets of suprabony defects. METHODS: Randomized
      Clinical Trials comparing open flap debridement (OFD) versus EMD in periodontal
      suprabony defects were identified through electronic and manual search.
      Screening, data extraction and quality assessment were conducted. The primary
      outcome measures were tooth survival (TS) and clinical attachment level (CAL)
      gain. Pocket probing depth (PPD) reduction and recession (REC) increase were
      secondary outcome measures. Information concerning clinical and radiological bone
      gain was also collected. RESULTS: The search identified 1170 studies, three
      articles reporting on (99 subjects/358 teeth) met the inclusion criteria and were
      included. No tooth was lost during follow-up (8-12 months). The adjunctive mean
      benefit of EMD was: 1.2 mm for CAL gain [confidence interval (CI): (0.9, 1.4), p
      < 0.00001, I(2) = 66%], 1.2 mm for the PPD reduction (CI: [0.8, 1.5], p < 0.0001,
      I(2) = 0%), -0.5 mm for the REC increase (CI: [-0.8, -0.2], p = 0.003, I(2) =
      0%). Potential risk of bias was identified. CONCLUSIONS: No differences were
      noted in TS but EMD application resulted in clinical and radiographic additional
      benefits compared to OFD alone. Nevertheless, the paucity of data, the risk of
      methodological and potential publication bias suggests caution in interpreting
      these results while supporting multicenter studies for this specific application.

PMID- 24329868
TI  - Self-reported recent testing and diagnosis for sexually transmitted infections
      among regular ecstasy users in Australia, 2011-2012.
AB  - BACKGROUND: Previous studies suggest that people who consume alcohol and drugs
      are at increased risk of sexually transmitted infections (STI). We examined the
      prevalence and predictors of self-reported STI testing and diagnosis among self
      reported regular ecstasy users (REU). METHODS: Nine hundred and fifty-five REUs
      from the 2011 and 2012 Ecstasy and Related Drugs Reporting System were included
      in the analysis. Bivariate and multivariate Poisson regression were used to
      identify predictors of recent STI testing, and logistic regression was used to
      identify predictors of recent STI diagnosis. RESULTS: Forty-four per cent of REUs
      reported having a recent STI test, and 5% reported a recent diagnosis. Of the 421
      REUs who reported a recent test, 10% reported a recent STI diagnosis. In
      multivariate analysis, REUs were more likely to report a recent STI test if they
      were female versus male [risk ratio (RR) = 1.56; 95% confidence interval (CI) =
      1.36-1.80], aged 25-29 years versus 16-19 years (RR = 1.34; 95% CI = 1.05-1.72),
      or reported >=2 casual sex partners versus no casual partners (RR = 1.48; 95% CI
      = 1.01-2.14). REUs reporting cannabis use in the past six months were 0.78 times
      less likely to report a recent STI test (95% CI = 0.66-0.94). There were no
      significant predictors associated with STI diagnosis. CONCLUSION: Encouragingly,
      REUs who reported having multiple casual partners in the past six months were
      more likely to report a recent test. However, younger REUs aged 16-19 years were
      least likely to test, suggesting health promotion needs to be directed to this
      age group. Further research is required to explain the lower testing among
      cannabis users.

PMID- 24329869
TI  - Conflicting selection on the timing of germination in a natural population of
      Arabidopsis thaliana.
AB  - The timing of germination is a key life-history trait that may strongly influence
      plant fitness and that sets the stage for selection on traits expressed later in
      the life cycle. In seasonal environments, the period favourable for germination
      and the total length of the growing season are limited. The optimal timing of
      germination may therefore be governed by conflicting selection through survival
      and fecundity. We conducted a field experiment to examine the effects of timing
      of germination on survival, fecundity and overall fitness in a natural population
      of the annual herb Arabidopsis thaliana in north-central Sweden. Seedlings were
      transplanted at three different times in late summer and in autumn covering the
      period of seed germination in the study population. Early germination was
      associated with low seedling survival, but also with high survival and fecundity
      among established plants. The advantages of germinating early more than balanced
      the disadvantage and selection favoured early germination. The results suggest
      that low survival among early germinating seeds is the main force opposing the
      evolution of earlier germination and that the optimal timing of germination
      should vary in space and time as a function of the direction and strength of
      selection acting during different life-history stages. 

PMID- 24329870
TI  - Perceptions of partners' attributions for depression in relation to perceptions
      of support and conflict in romantic relationships.
AB  - People's attributions for their own psychological problems are linked to their
      interpersonal behaviors and attitudes. However, depressed individuals' inferences
      about their romantic partners' attributions for their depressive symptoms have
      yet to be studied in relation to their perceptions of relationship quality. This
      study examined perceived support from and conflict with partners in relation to
      perceptions of partners' attributions for depression in 165 individuals
      experiencing at least mild depressive symptoms. After controlling for relevant
      demographic characteristics, perceived internal/controllable psychological
      attributions were related to greater perceived conflict and lower perceived
      support, and perceived controllable biological attributions were related to
      greater perceived conflict. Perceived external/uncontrollable psychological and
      uncontrollable biological attributions were unrelated to perceived support and
      conflict. Findings suggest that perceived attributions may help explain the link
      between depression, support, and conflict in romantic relationships. 

PMID- 24329871
TI  - A global analysis of bidirectional interactions in alpine plant communities shows
      facilitators experiencing strong reciprocal fitness costs.
AB  - Facilitative interactions are defined as positive effects of one species on
      another, but bidirectional feedbacks may be positive, neutral, or negative.
      Understanding the bidirectional nature of these interactions is a fundamental
      prerequisite for the assessment of the potential evolutionary consequences of
      facilitation. In a global study combining observational and experimental
      approaches, we quantified the impact of the cover and richness of species
      associated with alpine cushion plants on reproductive traits of the benefactor
      cushions. We found a decline in cushion seed production with increasing cover of
      cushion-associated species, indicating that being a benefactor came at an overall
      cost. The effect of cushion-associated species was negative for flower density
      and seed set of cushions, but not for fruit set and seed quality. Richness of
      cushion-associated species had positive effects on seed density and modulated the
      effects of their abundance on flower density and fruit set, indicating that the
      costs and benefits of harboring associated species depend on the composition of
      the plant assemblage. Our study demonstrates 'parasitic' interactions among
      plants over a wide range of species and environments in alpine systems, and we
      consider their implications for the possible selective effects of interactions
      between benefactor and beneficiary species. 

PMID- 24329872
TI  - Care zoning in a psychiatric intensive care unit: strengthening ongoing clinical
      risk assessment.
AB  - AIMS AND OBJECTIVES: To implement and evaluate the care zoning model in an eight
      bed psychiatric intensive care unit and, specifically, to examine the model's
      ability to improve the documentation and communication of clinical risk
      assessment and management. BACKGROUND: Care zoning guides nurses in assessing
      clinical risk and planning care within a mental health context. Concerns about
      the varying quality of clinical risk assessment prompted a trial of the care
      zoning model in a psychiatric intensive care unit within a regional mental health
      facility. The care zoning model assigns patients to one of 3 'zones' according to
      their clinical risk, encouraging nurses to document and implement targeted
      interventions required to manage those risks. DESIGN: An implementation trial
      framework was used for this research to refine, implement and evaluate the impact
      of the model on nurses' clinical practice within the psychiatric intensive care
      unit, predominantly as a quality improvement initiative. METHODS: The model was
      trialled for three months using a pre- and postimplementation staff survey, a
      pretrial file audit and a weekly file audit. Informal staff feedback was also
      sought via surveys and regular staff meetings. RESULTS: This trial demonstrated
      improvement in the quality of mental state documentation, and clinical risk
      information was identified more accurately. There was limited improvement in the
      quality of care planning and the documentation of clinical interventions. Nurses'
      initial concerns over the introduction of the model shifted into overall
      acceptance and recognition of the benefits. CONCLUSIONS: The results of this
      trial demonstrate that the care zoning model was able to improve the consistency
      and quality of risk assessment information documented. Care planning and
      evaluation of associated outcomes showed less improvement. RELEVANCE TO CLINICAL
      PRACTICE: Care zoning remains a highly applicable model for the psychiatric
      intensive care unit environment and is a useful tool in guiding nurses to carry
      out routine patient risk assessments.

PMID- 24329873
TI  - The emerging importance of microbial volatile organic compounds.

PMID- 24329874
TI  - Post-operative complications requiring hospitalization more than one yr after
      living donor liver transplantation.
AB  - BACKGROUND/PURPOSE: The long-term outcomes after living donor liver
      transplantation (LDLT) have not been clearly established. This retrospective
      study assessed long-term outcomes after LDLT through reviewing complications
      requiring hospitalization more than one yr after engraftment. METHODS: Sixty-five
      LDLT recipients alive more than one yr post-transplantation were enrolled, 37
      males and 28 females, with a median age at transplantation of 53 yr (range, 0-68
      yr). We reviewed all post-operative complications requiring hospitalization more
      than one yr after LDLT. RESULTS: There were 61 post-operative complications
      requiring hospitalization in 43 of the 65 patients (66%), and the majority of
      these complications were transplantation related (59/61; 97%). Despite this, 43
      (78%) of 55 surviving patients had normal liver function at their last follow-up,
      and 50 patients (91%) achieved normal activity (Karnofsky score 100%).
      CONCLUSIONS: More than one-half of our LDLT recipients required hospitalization
      more than one yr post-LDLT to treat a complication. Most were able to maintain
      their quality of life and liver function with appropriate treatment.

PMID- 24329876
TI  - Novel nonsense mutation in MSX1 in familial nonsyndromic oligodontia: subcellular
      localization and role of homeodomain/MH4.
AB  - Nonsyndromic tooth agenesis is one of the most common anomalies in human
      development. Part of the malformation is inherited and is associated with paired
      box 9 (PAX9), msh homeobox 1 (MSX1), and axin 2 (AXIN2) mutations. To obtain a
      comprehensive understanding of the genetic and molecular mechanisms that underlie
      this genetic disease, we investigated six familial and seven sporadic Japanese
      cases of nonsyndromic tooth agenesis. Searches for mutations in these candidate
      genes detected a novel nonsense mutation (c.416G>A) in exon 1 of MSX1 from a
      family with oligodontia. This mutation co-segregated in the affected family
      members. Moreover, this mutation produced a termination codon in the first exon
      and therefore the gene product (W139X) was truncated at the C terminus, hence,
      the entire homeodomain/MH4, which has many functions, such as DNA binding,
      protein-protein interaction, and nuclear localization, was absent. We
      characterized the properties of this truncated MSX1 by investigating the
      subcellular localization of the mutant gene product in transfected cells. The
      wild-type MSX1 localized exclusively at the nuclear periphery of transfected
      cells, whereas the mutant MSX1 was stable but localized diffusely throughout the
      whole cell. These results indicate that W139X MSX1 is responsible for tooth
      agenesis. 

PMID- 24329878
TI  - The role of hydrolysates for allergy prevention--pro.

PMID- 24329879
TI  - Impact of suspected food allergy on emotional distress and family life of parents
      prior to allergy diagnosis.
AB  - BACKGROUND: Food allergy is associated with psychological distress in both child
      and parent. It is unknown whether parental distress is present prior to clinical
      diagnosis or whether experiences at clinic can reduce any distress present. This
      study aimed to assess anxiety and depression in parents and the impact of
      suspected food allergy on the lives of families before and after a visit to an
      allergy clinic. METHODS: One hundred and twenty-four parents visiting an allergy
      clinic for the first time to have their child assessed for food allergy completed
      a study-specific questionnaire and the Hospital Anxiety and Depression Scale; 50
      parents completed these 4-6 wk later in their own home. RESULTS: Most parents
      (86.4%) reported suspected food allergy had an impact on their family life prior
      to clinic attendance; 76% had made changes to their child's diet. 32.5% of
      parents had mild-to-severe anxiety before their clinic visit; 17.5% had mild-to
      moderate depression. Post-clinic, 40% had mild-to-severe anxiety; 13.1% had mild
      to-moderate depression. There were no significant differences in anxiety (p =
      0.34) or depression scores (p = 0.09) before and after the clinic visit.
      CONCLUSIONS: Anxiety and depression is present in a small proportion of parents
      prior to diagnosis of food allergy in their child and this does not reduce in the
      short term after the clinic visit. Identification of parents at risk of suffering
      from distress is needed and ways in which we communicate allergy information
      before and at clinic should be investigated to see if we can reduce distress.

PMID- 24329875
TI  - Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis.
AB  - High serum/plasma cholesterol levels have been suggested as a risk factor for
      Alzheimer's disease (AD). Some reports, mostly retrospective epidemiological
      studies, have observed a decreased prevalence of AD in patients taking the
      cholesterol lowering drugs, statins. The strongest evidence causally linking
      cholesterol to AD is provided by experimental studies showing that
      adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid
      beta-protein (Ab) levels. However, there are problems with the cholesterol-AD
      hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not
      support cholesterol as a causative factor in AD.Prospective studies on statins
      and AD have largely failed to show efficacy. Even the experimental data are open
      to interpretation given that it is well-established that modification of
      cholesterol levels has effects on multiple proteins, not only amyloid precursor
      protein and Ab. The purpose of this review, therefore, was to examine the above
      mentioned issues, discuss the pros and cons of the cholesterol-AD hypothesis,
      involvement of other lipids in the mevalonate pathway, and consider that AD may
      impact cholesterol homeostasis.

PMID- 24329880
TI  - Recent advances in the understanding of sepsis-induced alterations in the
      neuroendocrine system.
AB  - Sepsis is a fatal systemic inflammatory disease. It is caused by an immune system
      inflammatory response to the entry of microorganisms or their products into the
      blood circulatory system. The pathophysiological mechanisms of sepsis are still
      poorly understood. The presence of microorganisms in the systemic circulation
      causes activation of the immune system, which in turn leads to a robust release
      of inflammatory cytokines. These inflammatory cytokines result in alterations
      across all important physiological systems, including the neuroendocrine system.
      Neuroendocrine responses differ between the acute and the late phase of sepsis.
      In the acute phase there are robust alterations in the secretion of
      neuroendocrine hormones in response to body demand. In the late phase, the plasma
      concentrations of some hormones remain low, despite heavy systemic demand,
      whereas several others increase despite of diminished needs. In this review, we
      give a brief overview on sepsis-induced major alterations in neuroendocrine
      secretions, and summarize current knowledge about mechanisms and targets for
      their treatment. 

PMID- 24329881
TI  - C9ORF72 hexanucleotide repeat expansion as a rare cause of bipolar disorder.

PMID- 24329882
TI  - Sleep enhances memory consolidation in children.
AB  - Sleep is an active state that plays an important role in the consolidation of
      memory. It has been found to enhance explicit memories in both adults and
      children. However, in contrast to adults, children do not always show a sleep
      related improvement in implicit learning. The majority of research on sleep
      dependent memory consolidation focuses on adults; hence, the current study
      examined sleep-related effects on two tasks in children. Thirty-three typically
      developing children aged 6-12 years took part in the study. Actigraphy was used
      to monitor sleep. Sleep-dependent memory consolidation was assessed using a novel
      non-word learning task and the Tower of Hanoi cognitive puzzle, which involves
      discovering an underlying rule to aid completion. Children were trained on the
      two tasks and retested following approximately equal retention intervals of both
      wake and sleep. After sleep, children showed significant improvements in
      performance of 14% on the non-word learning task and 25% on the Tower of Hanoi
      task, but no significant change in score following the wake retention interval.
      Improved performance on the Tower of Hanoi may have been due to children
      consolidating explicit aspects of the task, for example rule-learning or memory
      of previous sequences; thus, we propose that sleep is necessary for consolidation
      of explicit memory in children. Sleep quality and duration were not related to
      children's task performance. If such experimental sleep-related learning
      enhancement is generalizable to everyday life, then it is clear that sleep plays
      a vital role in children's educational attainment. 

PMID- 24329883
TI  - Predictors associated with treatment initiation and switch in a real-world
      chronic hepatitis B population from five European countries.
AB  - In Europe, healthcare systems differ between countries and different factors may
      influence Chronic hepatitis B (CHB) treatment choices in different counties. This
      analysis from a prospective, longitudinal, non-interventional study in five EU
      countries aimed to explore determinants associated with treatment initiation or
      switch in patients with CHB. A total of 1267 adult patients with compensated CHB
      in Germany, France, Poland, Romania and Turkey were prospectively followed for up
      to 2 years (March 2008-December 2010). Determinants of treatment initiation or
      switch were analysed using multivariate Cox proportional hazards regression.
      Median time since CHB diagnosis was 2.6 (0-37.7) years. Among 646 treatment-naive
      patients, the probability of treatment initiation during follow-up was higher: in
      Germany (P = 0.0006), Poland (P < 0.0001) and Romania (P = 0.0004) compared with
      Turkey; in patients with alanine transaminase (ALT) 1-2 * upper limit of normal
      (ULN) (P = 0.0580) or >2 * ULN (P = 0.0523) compared with ALT <= 1 * ULN; and in
      patients with hepatitis B virus (HBV) DNA >= 2000 IU/mL (P < 0.0001) compared
      with HBV DNA <2000 IU/mL or undetectable. Among 567 treated patients, 87 switched
      treatment during follow-up. The probability of treatment switch was higher: in
      France (P = 0.0029), Germany (P = 0.0078) and Poland (P = 0.0329) compared with
      Turkey; and in patients with HBV DNA <2000 (P < 0.0001) or >= 2000 IU/mL (P <
      0.0001), compared with undetectable. Viral load and ALT level were identified as
      the major drivers of treatment initiation. HBV DNA level was also a significant
      determinant of treatment switch. Results were statistically different across EU
      countries.

PMID- 24329884
TI  - Trypanosoma cruzi infection in a non-endemic country: epidemiological and
      clinical profile.
AB  - Chagas disease has been increasingly diagnosed in non-endemic countries. This is
      a prospective observational study performed at the Tropical Medicine Units of the
      International Health Program of the Catalan Health Institute, Barcelona (PROgrama
      de Salud Internacional del Instituto Catalan de la Salud, PROSICS Barcelona,
      Spain), that includes all patients with Chagas disease who attended from June
      2007 to May 2012. Clinical and epidemiological data were collected. Overall, 1274
      patients were included, the mean age of the patients was 37.7 years, 67.5% were
      women and 97% came from Bolivia. Thirteen patients had immunosuppressive
      conditions. The prevalence of cardiac involvement was 16.9%, lower than in
      previous studies performed in endemic areas (20-60%). Cardiac alterations were
      found in 33.8% of symptomatic and 14.1% of asymptomatic patients. The prevalence
      of digestive involvement was 14.8%. The rate of digestive involvement is very
      different among previous studies because of different diagnostic tools and
      strategies used. Barium enema alterations were found in 21.4% of symptomatic and
      10.3% of asymptomatic patients, and oesophageal alterations were found in 3.7% of
      symptomatic and in 2.3% of asymptomatic patients. As shown in previous studies,
      Chagas disease in non-endemic countries affects younger patients and has lower
      morbidity.

PMID- 24329885
TI  - A novel and rapid loop-mediated isothermal amplification assay for the specific
      detection of Verticillium dahliae.
AB  - AIMS: In this study, a loop-mediated isothermal amplification (LAMP) assay has
      been developed and evaluated for the rapid and sensitive detection of
      Verticillium dahliae Kleb., the causal agent of vascular wilts in many
      economically important crops. METHODS AND RESULTS: LAMP primers were designed
      based on a previously described RAPD marker, and the LAMP assay was applied for
      direct detection of V. dahliae grown on medium and from soil samples without DNA
      purification steps (direct-LAMP). Thirty-two agricultural soil samples from
      various olive orchards were collected, and the presence of pathogen was detected
      by LAMP, direct-LAMP and nested-PCR methods. The LAMP methodology could
      successfully detect V. dahliae with high specificity, and cross-reaction was not
      observed with different pathogenic and nonpathogenic fungi and bacteria. The LAMP
      assay was capable of detecting a minimum of 500 and 50 fg of purified target DNA
      per reaction of V. dahliae ND and D pathotypes, respectively. In contrast, nested
      PCR could only detect 5 pg reaction(-1) for both pathotypes. In artificially
      infested soil samples, the LAMP method detected 5 microsclerotia per gram of
      soil. Conversely, nested-PCR assay detected 50 microsclerotia g(-1) soil. The
      detection ratios of LAMP and direct-LAMP protocols were better (26 and 24
      positive samples out of 32 agricultural soils analysed, respectively) than that
      obtained for nested-PCR method (22 positive results). Moreover, direct-LAMP
      yielded positive detection of V. dahliae in agricultural soil samples within 60
      80 min. CONCLUSIONS: The newly developed LAMP method was proved to be an
      effective, simple and rapid method to detect V. dahliae without the need for
      either expensive equipment or DNA purification. SIGNIFICANCE AND IMPACT OF STUDY:
      This technique can be considered as an excellent standard alternative to plating
      and nested-PCR assays for the early, sensitive and low-cost detection of V.
      dahliae as well as other soilborne pathogens in the field.

PMID- 24329886
TI  - What's my line? A narrative review and synthesis of the literature on Registered
      Nurses' communication behaviours between shifts.
AB  - AIM: To describe, appraise and synthesize the seminal and empirical literature
      around Registered Nurses' communication behaviours between shifts in acute
      hospital settings. BACKGROUND: Effective communication between shifts (at nursing
      handover) is acknowledged as a prerequisite to safe and high-quality patient
      centred care. However, gaps and inconsistencies continue to prevail. DESIGN:
      Narrative review and synthesis. DATA SOURCES: The electronic databases PubMED,
      CINAHL and Scopus were used. REVIEW METHODS: English language, peer-reviewed
      papers published between 1970-April 2012 were considered for review. Criteria
      included Registered Nurses' communication during handovers in adult hospital
      settings. RESULTS: Twenty-nine papers were reviewed. The research lacks a clear
      conceptual framework to define the core purposes of Nurses' communication
      behaviours between shifts. Seven themes were identified: overall purpose; report
      givers and receivers; seeing the whole picture; teaching and education; language;
      patient-centred care; and social cohesion. Two main communication processes are
      required - one articulating the whole picture and the other detailing information
      about patients. CONCLUSION: This area of research is challenged by lack of
      consistency in terminology and methodological rigour. While recent research has
      confirmed the findings from the seminal work, it has not been able to elaborate
      on some of the key challenges to refine the knowledge base. A more integrated
      approach is required to understand the complex process of improving nursing
      communication behaviours, particularly around the nursing handover. A neglected
      area of study is the role of the unit lead in determining the communication
      standards of the whole nursing team.

PMID- 24329887
TI  - Genetic correction using engineered nucleases for gene therapy applications.
AB  - Genetic mutations in humans are associated with congenital disorders and
      phenotypic traits. Gene therapy holds the promise to cure such genetic disorders,
      although it has suffered from several technical limitations for decades. Recent
      progress in gene editing technology using tailor-made nucleases, such as
      meganucleases (MNs), zinc finger nucleases (ZFNs), TAL effector nucleases
      (TALENs) and, more recently, CRISPR/Cas9, has significantly broadened our ability
      to precisely modify target sites in the human genome. In this review, we
      summarize recent progress in gene correction approaches of the human genome, with
      a particular emphasis on the clinical applications of gene therapy. 

PMID- 24329888
TI  - Editorial: bridging gaps between basic research and clinical practice.
AB  - Over the past several decades, child psychology and psychiatry has witnessed an
      explosion in the volume of, and a decided quickening in the pace of,
      dissemination of research findings. On the one hand, this has led us to an
      enviable position. 

PMID- 24329890
TI  - Commentary: Diverging trajectories from a similar starting point: the outcome in
      adults whose autism was diagnosed in childhood--reflections on Howlin et al.
      (2013).
AB  - Howlin and colleagues are to be congratulated on a further follow up from the
      cohort of children first diagnosed by Rutter at the age of 2-13 years nearly 40
      years ago (Howlin, Savage, Moss, Tempier, & Rutter, 2013).

PMID- 24329892
TI  - Swallowing dysfunction and autonomic nervous system dysfunction in Alzheimer's
      disease: a scoping review of the evidence.
AB  - OBJECTIVES: To describe, synthesize, and interpret literature on swallowing
      impairment (dysphagia) and autonomic nervous system (ANS) dysfunction in
      Alzheimer's disease (AD) and to identify gaps in the existing literature. DESIGN:
      Scoping review of literature covering several study designs. SETTING: Literature
      review. PARTICIPANTS: Individuals with AD. MEASUREMENTS: Systematic searches of
      the PubMed, EBSCOhost, PsychINFO, Cochrane, EMBASE, and Scopus databases were
      conducted. Literature was identified and organized into categories. Studies were
      then evaluated using the Oxford Centre for Evidence-Based Medicine Levels of
      Evidence criteria. After evaluation, the literature was synthesized to form
      conclusions and identify knowledge gaps. RESULTS: Ninety-five articles met the
      study criteria and were included in the review. Thirty-one studies examining
      dysphagia in AD provide preliminary evidence on the prevalence, nature, and
      treatment of dysphagia in AD; knowledge gaps were identified with respect to
      demographic characteristics, nature of dysphagia, functional significance,
      assessment, treatment, and underlying mechanisms of dysphagia in AD. Sixty-four
      studies of ANS dysfunction in AD were reviewed, of which 49 identified at least
      one variable reflecting ANS dysfunction in AD. Knowledge gaps were identified
      related to demographics, functional significance, and underlying neural
      mechanisms. No studies were found that examined both dysphagia and ANS
      dysfunction in AD. CONCLUSION: Current evidence indicates that swallowing
      impairment, as well as ANS dysfunction, may occur in AD. Potential relationships
      between dysphagia and ANS dysfunction in AD have not been examined. Future
      research should explore the possibility that swallowing and ANS dysfunction in AD
      are related.

PMID- 24329893
TI  - Identification of human tear fluid biomarkers in vernal keratoconjunctivitis
      using iTRAQ quantitative proteomics.
AB  - BACKGROUND: Understanding and treating vernal keratoconjunctivitis (VKC) has been
      a challenge because the pathogenesis is unclear and antiallergic therapy often
      unsuccessful. The aim of the study was to analyze peptide profiles in human tears
      using mass spectrometry to elucidate compositional differences between healthy
      subjects and patients affected by VKC. METHODS: Tears were collected from healthy
      subjects and VKC patients. Digested samples were treated with iTRAQ (isobaric tag
      for relative and absolute quantitation). Separation of tryptic peptides was
      realized using a MicroHPLC interfaced with a microfraction collector. MS and
      MS/MS mass spectra were performed using a MALDI TOF/TOF 4800 Applied Biosystem
      spectrometer. Protein PilotTM software with ParagonTM algorithm v4.1.46 or GPSTM
      with Mascot engine was used as search engines with SwissProt or IPI human as the
      databases. RESULTS: A significant number of peptides were examined, and 78
      proteins were successfully identified. In all VKC samples, levels of serum
      albumin, transferrin, and hemopexin were found up to 100 times higher than
      control tear levels and correlated to the severity of disease. Hemopexin,
      transferrin, mammaglobin B, and secretoglobin 1D were found significantly over
      expressed in VKC samples compared with the control samples. Tear samples from
      patients treated with topical cyclosporine or corticosteroids showed a dramatic
      reduction in these protein levels. CONCLUSIONS: LC MALDI MS and isobaric tag for
      relative and absolute quantitation technique may be useful in the quantitative
      and qualitative characterization of the peptidoma of human tears. These
      techniques may identify target proteins to be used in the diagnosis and
      management of VKC and other inflammatory ocular surface conditions.

PMID- 24329894
TI  - Photoassociative spectroscopy of laser-cooled atoms.

PMID- 24329895
TI  - Nestin expression throughout multistep pathogenesis of multiple myeloma.
AB  - The stem cell marker nestin (NES) is found in dividing cells of developing and
      regenerating tissues. Upon terminal differentiation, NES expression is diminished
      but may be re-expressed following injury or in cancer. Surprisingly, we recently
      confirmed NES as a tumour-specific marker for mature CD138(+) 38(+) plasma cells
      (PC) in multiple myeloma (MM). The present study analysed NES expression
      throughout the spectrum of MM developmental stages, starting with individuals
      with no haematological malignancy, through monoclonal gammopathy of undetermined
      significance (MGUS) and MM to plasma cell leukaemia (PCL) and MM cell lines. NES
      was analysed in bone marrow PC of 163 MM, four PCL and nine MGUS patients, 10
      individuals with no haematological malignancy and 6 myeloma cell lines (OPM-2,
      RPMI-8226, MOLP-8, U-266, EJM, NCI-H929) by flow cytometry and/or real-time
      polymerase chain reaction or immunochemistry. We observed a tendency of increased
      NES expression in parallel with disease progression. NES was evaluated as a
      reliable marker for accurate discrimination between MM patients and the control
      group. High NES levels were strongly associated with the presence of 1q21 gain.
      For the first time, NES was demonstrated to predict worse response to
      conventional therapy/novel agents. These results suggest that NES might become a
      useful clinical parameter with an important role in MM pathogenesis. 

PMID- 24329897
TI  - Metabolomic analysis reveals the potential metabolites and pathogenesis involved
      in mulberry yellow dwarf disease.
AB  - To analyse the molecular mechanisms of phytoplasma pathogenicity, the
      comprehensive metabolomic changes of mulberry leaf and phloem sap in response to
      phytoplasma infection were examined using gas chromatography-mass spectrometry.
      The metabolic profiles obtained revealed that the metabolite compositions of leaf
      and phloem sap were different, and phytoplasma infection has a greater impact on
      the metabolome of phloem sap than of leaf. Phytoplasma infection brought about
      the content changes in various metabolites, such as carbohydrates, amino acids,
      organic acids, etc. Meanwhile, the results of biochemical analysis showed that
      the degradation of starch was repressed, and the starch content was increased in
      the infected leaves. In addition, we found that phytoplasma infection changed the
      levels of abscisic acid and cytokinin and break phytohormone balance.
      Interestingly, our data showed that the contents of H2O2 and superoxide were
      increased in the infected leaves, but not in the phloem saps. Based on the
      results, the expression levels of the genes involved in the metabolism of some
      changed metabolites were examined, and the potential molecular mechanisms of
      these changes were discussed. It can be concluded that both the leaf and phloem
      saps have a complicated metabolic response to phytoplasma infection, but their
      response mechanisms were different.

PMID- 24329896
TI  - Respiratory cycle entrainment of septal neurons mediates the fast coupling of
      sniffing rate and hippocampal theta rhythm.
AB  - Memory for odour information may result from temporal coupling between the
      olfactory and hippocampal systems. Respiration defines the frequency of olfactory
      perception, but how the respiratory rate affects hippocampal oscillations remains
      poorly understood. The afferent connectivity of the medial septum/diagonal band
      of Broca complex (MS/DB) proposes this region as a crossroads between respiratory
      and limbic pathways. Here we investigate if the firing rates of septal neurons
      integrate respiratory rate signals. We demonstrate that approximately 50% of
      MS/DB neurons are temporally correlated with sniffing frequency. Moreover, a
      group of slow-spiking septal neurons are phase-locked to the sniffing cycle. We
      show that inter-burst intervals of MS/DB theta cells relate to the sniff rate.
      Intranasal odour infusion evokes sniff phase preference for the activity of fast
      spiking MS/DB neurons. Concurrently, the infusion augments the correlation
      between sniffing and limbic theta oscillations. During periods of sniffing-theta
      correlation, CA1 place cells fired preferentially during the inhalation phase,
      suggesting the theta cycle as a coherent time frame for central olfactory
      processing. Furthermore, injection of the GABAergic agonist muscimol into medial
      septum induces a parallel decrease of sniffing and theta frequencies. Our
      findings provide experimental evidence that MS/DB does not merely generate theta
      rhythm, but actively integrates sensorimotor stimuli that reflect sniffing rate.
      Such integration may provide temporal oscillatory synchronisation of MS/DB
      innervated limbic structures with the sniffing cycle. 

PMID- 24329898
TI  - Diagnostic evaluation of hypersensitivity reactions to beta-lactam antibiotics in
      a large population of children.
AB  - INTRODUCTION: Hypersensitivity reactions to beta-lactams (BLs) are often reported
      in children, with amoxicillin and, to a lesser extent, cephalosporins being the
      most frequent drugs involved. Although many of these children are considered to
      be allergic, a careful evaluation only confirms a low percentage. OBJECTIVES: To
      analyse the clinical data, sensitization profile and diagnostic methods used in a
      large group of children with a clinical history of hypersensitivity reactions to
      BLs. METHODS: The study included children aged 1-14 yr with symptoms suggestive
      of hypersensitivity to BLs from January 2006-December 2012. Diagnosis was
      confirmed from a clinical history, specific IgE determination, skin testing and,
      if necessary, a drug provocation test (DPT). RESULTS: Of a total of 783 patients
      studied, only 62 (7.92%) were confirmed as being allergic, 9 (14.52%) with
      immediate and 53 (85.48%) with non-immediate reactions. In those with immediate
      reactions, 2 (22.22%) were diagnosed by in vitro test, 2 (22.22%) by skin testing
      and 5 (55.56%) by DPT; in those with non-immediate reactions, 2 (3.77%) were
      diagnosed by skin testing and 51 (96.23%) by DPT. In all cases, DPT was positive
      to the culprit drug (29 AX-CLV, 26 AX, 1 cefixime and 1 cefaclor), and the most
      usual symptoms were exanthema in 43 cases, urticaria in 12, urticaria-angio
      oedema in 1 and erythema in 1 case. CONCLUSION: After an allergological work-up,
      over 90% of the children evaluated were finally confirmed as tolerant to BLs.
      Most reactions were of the non-immediate type, and DPT was an essential tool for
      diagnosis.

PMID- 24329899
TI  - Hypercalcemia in renal transplant patients: prevalence and management in Canadian
      transplant practice.
AB  - Hypercalcemia, occurring in up to 25% of patients within 12 months following
      renal transplantation, and persistent hyperparathyroidism were evaluated
      following renal transplantation, by retrospective chart review of 1000 adult
      patients transplanted between January 1, 2003 and January 31, 2008 with at least
      six months follow-up. Serum calcium, parathyroid hormone, and phosphate levels
      were recorded at 12, 24, 36, and 48 months. Average follow-up was 766 (535) d
      (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor
      57%. Point prevalence of hypercalcemia (serum Ca(2+) > 2.6 mM) was 16.6% at month
      12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence
      of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month
      24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration
      rate (GFR) was maintained throughout and was not different between patients with
      or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of
      patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy
      was performed in 112/1000 patients, 15 post-transplant. Persistent
      hyperparathyroidism, often accompanied by hypercalcemia, is common following
      successful renal transplantation, but the lack of clear management suggests the
      need for further study and development of evidence-based guidelines.

PMID- 24329900
TI  - Sensory evolution of hearing in tettigoniids with differing communication
      systems.
AB  - In Tettigoniidae (Orthoptera: Ensifera), hearing organs are essential in mate
      detection. Male tettigoniids usually produce calling songs by tegminal
      stridulation, whereas females approach the males phonotactically. This
      unidirectional communication system is the most common one among tettigoniids. In
      several tettigoniid lineages, females have evolved acoustic replies to the male
      calling song which constitutes a bidirectional communication system. The genus
      Poecilimon (Tettigoniidae: Phaneropterinae) is of special interest because the
      ancestral state of bidirectional communication, with calling males and responding
      females, has been reversed repeatedly to unidirectional communication. Acoustic
      communication is mediated by hearing organs that are adapted to the conspecific
      signals. Therefore, we analyse the auditory system in the Tettigoniidae genus
      Poecilimon for functional adaptations in three characteristics: (i) dimension of
      sound-receiving structures (tympanum and acoustic spiracle), (ii) number of
      auditory sensilla and (iii) hearing sensitivity. Profound differences in the
      auditory system correlate with uni- or bidirectional communication. Among the
      sound-receiving structures, the tympana scale with body size, whereas the
      acoustic spiracle, the major sound input structure, was drastically reduced in
      unidirectional communicating species. In the unidirectional P. ampliatus group,
      auditory sensilla are severely reduced in numbers, but not in the unidirectional
      P. propinquus group. Within the P. ampliatus group, the number of auditory
      sensilla is further reduced in P. intermedius which lost acoustic signalling due
      to parthenogenesis. The auditory sensitivity correlated with the size of the
      acoustic spiracle, as hearing sensitivity was better with larger spiracles,
      especially in the ultrasonic range. Our results show a significant reduction in
      auditory structures, shaped by the differing sex roles during mate detection. 

PMID- 24329901
TI  - Catalytic and synergistic antibacterial potential of green synthesized silver
      nanoparticles: Their ecotoxicological evaluation on Poecillia reticulata.
AB  - In the present study, stable silver nanoparticles (AgNPs) were fabricated at a
      rapid rate from leaf extract of medicinally important plant Alstonia macrophylla.
      Biosynthesized AgNPs are of spherical shape and narrow size (70 nm), exhibiting a
      surface plasmon resonance peak at 435 nm, and a zeta potential of -30.8 mV and
      have a crystalline nature. A diverse biochemical consortium of protein,
      terpenoids, phenolics, and flavonoids in leaf extract of A. macrophylla was found
      to be responsible for AgNP synthesis as evidenced from qualitative-quantitative
      chemical analysis and Fourier transform infrared spectroscopy studies.
      Nitroaromatic compounds are anthropogenic pollutants with long-lasting
      environmental persistence and are needed to transform into less toxic
      derivatives. 4-Nitrophenol and p-nitroaniline were reduced to less hazardous and
      commercially useful 4-aminophenol and p-phenylenediamine by phytosynthesized
      AgNPs. Rate constants of 0.052 and 0.040 Min(-1) were calculated for 4
      nitrophenol and p-nitroaniline reduction, respectively. Thin-layer chromatography
      also confirms the reduction of these nitroaromatic compounds. Combinational
      studies could be one of the strategies to overcome microbial resistance to
      antibiotics. In synergistic antibacterial assay, the highest increase in a fold
      area of 3.84 was reported against Staphylococcus aureus using a combination of
      AgNPs with penicillin. Biosynthesized AgNPs were found to be less toxic (LC50 =
      9.13 ppm) than chemically synthesized AgNPs having a LC50 value of 2.86 ppm
      against nontarget fish Poecillia reticulata. Our green nanosynthesis method
      offers a faster rate of formation of stable AgNPs having antibacterial and
      catalytic potential with lower environmental toxicity. 

PMID- 24329902
TI  - Overexpression of a proton-coupled vacuolar glucose exporter impairs freezing
      tolerance and seed germination.
AB  - Arabidopsis vacuoles harbor, besides sugar transporter of the TMT-type, an early
      response to dehydration like 6 (ERDL6) protein involved in glucose export into
      the cytosol. However, the mode of transport of ERDL6 and the plant's feedback to
      overexpression of its activity on essential properties such as, for example, seed
      germination or freezing tolerance, remain unexplored. Using patch-clamp studies
      on vacuoles expressing AtERDL6 we demonstrated directly that this carrier
      operates as a proton-driven glucose exporter. Overexpression of BvIMP, the
      closest sugar beet (Beta vulgaris) homolog to AtERDL6, in Arabidopsis leads
      surprisingly to impaired seed germination under both conditions, sugar
      application and low environmental temperatures, but not under standard
      conditions. Upon cold treatment, BvIMP overexpressor plants accumulated lower
      quantities of monosaccharides than the wild-type, a response in line with the
      reduced frost tolerance of the transgenic Arabidopsis plants, and the fact that
      cold temperatures inhibits BvIMP transcription in sugar beet leaves. With these
      findings we show that the tight control of vacuolar sugar import and export is a
      key requisite for cold tolerance and seed germination of plants. 

PMID- 24329904
TI  - Tinea capitis mimicking dissecting cellulitis of the scalp: a histopathologic
      pitfall when evaluating alopecia in the post-pubertal patient.

PMID- 24329905
TI  - Everything you wanted to know about dermatofibroma but were afraid to ask.

PMID- 24329906
TI  - Rab7 is functionally required for selective cargo sorting at the early endosome.
AB  - The small GTPases of the Rab family act as a molecular switch regulating various
      aspects of membrane trafficking through the selective recruitment of effector
      proteins. Whereas Rab7 has been classically involved in the regulation of
      transport within the endolysosomal network, persistent controversy remains as to
      whether Rab7 also plays a role in earlier steps of endosomal trafficking. In this
      study, we show that Rab7 depletion or inactivation results in enlargement of both
      early and late endosomes. Rab7 depletion led to the retention of a significant
      fraction of internalized low-density lipoproteins (LDL) mainly in enlarged early
      endosomes (EE). As a result, LDL processing and the transcriptional regulation of
      sterol-sensitive genes were impaired. We found that Rab7 activity was also
      required for the sorting of the mannose-6-phosphate receptor, the interferon
      alpha-receptor and the Shiga toxin B-subunit. In contrast, epidermal growth
      factor (EGF) sorting at the EE or the recycling of transferrin and LDL-R were not
      affected by Rab7 depletion. Our findings demonstrate that in addition to
      regulating late endosomes (LE) to lysosomes transport, Rab7 plays a functional
      role in the selective sorting of distinct cargos at the EE and that the Rab5 to
      Rab7 exchange occurs early in the endosomal maturation process. 

PMID- 24329907
TI  - Intimate partner violence victimization and alcohol consumption in women: a
      systematic review and meta-analysis.
AB  - AIMS: To examine the evidence of association between intimate partner physical or
      sexual violence (IPV) victimization and alcohol consumption in women. METHODS: We
      conducted a systematic review and meta-analysis of cross-sectional and
      longitudinal studies released before 6 June 2013. Studies providing an estimate
      of association between violence and alcohol consumption or alcohol use disorders
      were eligible for inclusion. Quality was assessed and random effects meta
      analyses used to generate pooled odds ratios (OR) where appropriate. Higgins I(2)
      where P<0.10 was taken to indicate heterogeneity. RESULTS: Fifty-five studies
      providing 102 estimates of association met the inclusion criteria. Most estimates
      were not controlled for partner alcohol use and other key confounders. Seven
      longitudinal studies provided 12 estimates of the association between alcohol and
      subsequent IPV; nine of 12 estimates showed a direction of increased odds of
      subsequent IPV, pooled OR=1.27 [95% confidence interval (CI)=1.07-1.52], I(2)
      =0%, P=0.437. Nine longitudinal studies provided 15 estimates of association
      between IPV and subsequent alcohol use; 14 of 15 estimates showed a direction of
      increased odds of subsequent alcohol use, pooled OR=1.25 (95% CI 1.02-1.52),
      I(2)=0%, P=0.751. Cross-sectional studies showed an association between IPV and
      alcohol use, pooled OR=1.80, 95% CI 1.58-2.06, but with substantial
      heterogeneity, I(2)=60.8%, P<0.0001. Definition of alcohol use partly accounted
      for heterogeneity in cross-sectional estimates. CONCLUSIONS: There is a clear
      positive association between alcohol use and intimate partner physical or sexual
      violence victimization among women, suggesting a need for programming and
      research that addresses this link. However, the temporal direction of the
      association remains unclear. Longitudinal studies with multiple waves of data
      collection are needed.

PMID- 24329909
TI  - The effectiveness of discharge planning on the knowledge, clinical symptoms and
      hospitalisation frequency of persons with schizophrenia: a longitudinal study in
      two hospitals in Tehran, Iran.
AB  - AIMS AND OBJECTIVES: To investigate the effectiveness of discharge planning on
      the knowledge, clinical symptoms and frequency of hospitalisation of persons with
      schizophrenia. BACKGROUND: Discharge planning is associated with decreases in the
      duration of hospitalisation, readmission to hospitals and decreases in medical
      costs. Yet, there is little known about the effectiveness of discharge planning
      among persons with schizophrenia in Iran. DESIGN: Longitudinal clinical trial.
      METHODS: In this longitudinal clinical trial, 46 persons with schizophrenia
      admitted to psychiatric hospitals were selected and classified into either
      intervention or control groups. For the intervention group, the discharge
      planning was designed using the nursing process model. The intervention was
      implemented across six sessions in the hospital and six sessions in patient's
      home (up to three months after discharge). Friedman test, independent t-tests,
      chi-squared test, Mann-Whitney U-test and Mc-Nemar's test were used to analyse
      demographic characteristics, knowledge scores, clinical symptoms and the
      frequency of hospitalisation. RESULTS: The intervention group demonstrated
      improved clinical symptoms between the time of discharge and three months after
      discharge and had higher knowledge levels compared with the control group. In
      addition, the frequency of patients' hospitalisation preintervention and three
      months postintervention was statistically significantly lower in the intervention
      group, while no such differences were found among the control group during this
      same time period. CONCLUSION: This study suggests that there are a number of
      advantages to discharge planning including an increase in the knowledge of
      patients, a decline in clinical symptoms and a reduction in the frequency of
      admission to hospitals. RELEVANCE TO CLINICAL PRACTICE: Due to high frequency of
      relapse, rehospitalisation and high remedial costs of persons with schizophrenia,
      it is important to consider discharge planning as a therapeutic approach for
      patients.

PMID- 24329910
TI  - Risk assessment of dimethylfumarate residues in dwellings following contamination
      by treated furniture.
AB  - Recently, numerous cases of dermatitis induced by dimethylfumarate (DMFu) have
      been reported in Europe. DMFu has been used to prevent mold development in
      various items, although it is not registered as a biocide. In France, from
      October 2008 to December 2009, more than 100 cases were reported. Despite a ban
      on articles containing DMFu and the removal of potentially contaminated products,
      some people were still suffering from dermatitis or other health problems. The
      French Agency for Food, Environmental and Occupational Health & Safety was
      mandated to assess whether the existence in the past of DMFu-contaminated items
      in dwellings could continue to pose a threat to the health of inhabitants. A risk
      assessment was performed based on the classical risk analysis approach for
      environmental contaminants. Hazard assessment of DMFu with regard to its
      sensitizing properties was performed, based on human case reports collected in
      France between January 2009 and February 2010. For around half of the 132
      individual cases reported, the causal link to DMFu was considered at least
      probable. An Organisation for Economic Co-Operation and Development (OECD) local
      lymph node assay performed in a study on mice showed strong sensitizing potential
      for DMFu. Exposure was assessed by measuring DMFu in items sampled in preselected
      dwellings. These investigations demonstrated that DMFu exposure can persist after
      removal of the primary contaminated items. We therefore concluded that there was
      clearly a risk of skin reactions in patients previously sensitized to DMFu.
      Furthermore, the available data do not support the existence of significant
      health effects through the respiratory route. 

PMID- 24329908
TI  - Apurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth
      factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells.
AB  - Tumor angiogenesis contributes to inferior prognosis in osteosarcoma.
      Apurinic/apyrimidinic endonuclease 1 (APE1) and fibroblast growth factor 2 (FGF2)
      and its receptor 3 (FGFR3) signaling pathway plays an important role in the
      angiogenic process. In this study we observed that high expression of APE1, FGF2
      and FGFR3, and microvessel density are positively correlated with poor prognosis
      of osteosarcoma patients. Furthermore, the Cox model showed that the tumor size,
      FGF2 and its receptor 3 (FGFR3), and microvessel density were adverse prognostic
      factors. Based on our clinical data, and the fact that APE1 is involved in tumor
      angiogenesis, we hypothesize that it is very likely that APE1 may indirectly
      promote angiogenesis by upregulating fibroblast FGF2 and FGFR3. Our preliminary
      data show small interfering RNA-mediated silence of APE1 experiments, which
      further supports this hypothesis. APE1-small interfering RNA significantly
      inhibited tumor angiogenesis by downregulating in vitro expression of FGF2 and
      FGFR3 in human umbilical vein endothelial cells in Matrigel tube formation assay,
      and further inhibited tumor growth in vivo in a mouse xenograft model. Thus, the
      proposed APE1-FGF2 and FGFR3 pathway may provide a novel mechanism for regulation
      of FGF2 and FGFR3 by APE1 in tumor angiogenesis. 

PMID- 24329911
TI  - Preliminary study of video imaging of blood vessels in tissues lining the
      gingival sulcus in periodontally healthy individuals.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to obtain in vivo images of
      the microcirculation in tissues lining the gingival crevice in periodontally
      healthy volunteers and to assess the repeatability of the parameters measured.
      MATERIAL AND METHODS: Video microscopy images of the microcirculation of tissues
      lining the gingival crevice were obtained from 20 periodontally healthy
      volunteers. Images were obtained with a single 1 mm diameter 1 pitch gradient
      index lens with a high numerical aperture and with a plain glass lens and
      illumination with a green 525 nm light-emitting diode and recorded using a video
      microscope. RESULTS: The morphological features of the vessels (including vessel
      diameter, vessel density, loops, branches, dilated vessels) were similar to those
      described previously in other mammals. The Kappa values for the assessment of
      morphology of the vessels using the gradient index lens range from 0.83 for
      branching to 0.91 for dilated and using the glass lens 0.47 for branching and
      0.38 for dilated. CONCLUSIONS: This novel system allowed for a consistent and
      repeatable assessment of the gingival microvasculature. However, there was some
      evidence of possible pressure artefacts in those cases where the measurements of
      separation between vessels exceeded 150 MUm.

PMID- 24329912
TI  - An efficient and economical method for extraction of DNA amenable to
      biotechnological manipulations, from diverse soils and sediments.
AB  - AIMS: An attempt was made to optimize a new protocol for isolation of pure
      metagenomic DNA from soil samples. METHODS AND RESULTS: Various chemicals (FeCl3
      , MgCl2 , CaCl2 and activated charcoal) were tested for their efficacy in
      isolation of metagenomic DNA from different soil and compost samples. Among these
      trials, charcoal and MgCl2 when used in combination yielded highly pure DNA free
      from humic acids and other contaminants. The DNA extracted with the optimized
      protocol was readily digested, amplified and cloned. Moreover, compared with a
      well-established commercial DNA isolation kit (UltraCleanTM Soil DNA Isolation
      Kit), our method for DNA isolation was found to be economical. This demonstrated
      that the method developed can be applied to a wide variety of soil samples and
      allows handling of multiple samples at a given time. CONCLUSIONS: The optimized
      protocol developed has successfully yielded pure metagenomic DNA amenable to
      biotechnological manipulations. SIGNIFICANCE AND IMPACT OF THE STUDY: A user
      friendly and economical protocol for isolation of DNA from soil and compost
      samples has been developed.

PMID- 24329913
TI  - Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a
      prospective randomized double-blinded multicentre trial.
AB  - Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure,
      which likely is prevented by early lamivudine therapy. Even nonfulminant but
      severe acute hepatitis B can lead to significant morbidity and impaired quality
      of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a
      placebo-controlled trial. Patients with severe aHBV infection (ALT >10* ULN,
      bilirubin >85 MUm, prothrombin time >50%) were prospectively treated with
      lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The
      primary end point was time to bilirubin <34.2 MUm. Secondary end points were time
      to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT.
      Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were
      hospitalized. No individual progressed to hepatic failure; all but one patient
      achieved the primary end point. Due to smaller than expected patient numbers, all
      study end points did not become statistically significant between treatment arms.
      Median time end points [in days] were bilirubin <34.2 MUm (26.5 vs 32), ALT
      normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier
      recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and
      development of anti-HBs (119 vs 109). In all but two patients (one in every
      group), HBsAg clearance was reached in the study. Adverse events occurred more
      frequently during lamivudine therapy, but did not reach statistical significance.
      Lamivudine may ameliorate severe aHBV infection, but limited patient numbers
      prevented definite conclusions.

PMID- 24329914
TI  - Epigallocatechin-3-gallate prevents autoimmune-associated down- regulation of p21
      in salivary gland cells through a p53-independent pathway.
AB  - The submandibular salivary glands of non-obese diabetic (NOD) mice, a model for
      Sjogren's syndrome and type-1 diabetes, show an elevated level of proliferating
      cell nuclear antigen (PCNA), a protein involved in cell proliferation and repair
      of DNA damage. We reported previously that epigallocatechin-3-gallate (EGCG), the
      most abundant green tea catechin, normalizes the PCNA level. PCNA's activity can
      be regulated by the cyclin-dependent kinase inhibitor p21, which is also
      important for epithelial cell differentiation. In turn, expression of p21 and
      PCNA are partially regulated by Rb phosphorylation levels. EGCG was found to
      modulate p21 expression in epithelial cells, suggesting that EGCG-induced p21
      could be associated with down-regulation of PCNA in vivo. The current study
      examined the protein levels of p21 and p53 (which can up-regulate p21) in NOD
      mice fed with either water or EGCG, and the effect of EGCG on p21 and p53 in cell
      line models with either normal or defective Rb. In NOD mice, the p21 level was
      low, and EGCG normalized it. In contrast to HSG cells with functional Rb,
      negligible expression of p21 in NS-SVAC cells that lack Rb was not altered by
      EGCG treatment. Inhibition of p53 by siRNA demonstrated that p21 and p53 were
      induced independently in HSG cells by a physiological concentration range of
      EGCG, suggesting p53 could be an important but not conditional factor associated
      with p21 expression. In conclusion, PCNA and p21 levels are altered inversely in
      the NOD model for SS and in HSG cells, and warrant further study as candidate new
      markers for salivary dysfunction associated with xerostomia. Induction of p21 by
      EGCG could provide clinically useful normalization of salivary glands by
      promoting differentiation and reducing PCNA levels. 

PMID- 24329915
TI  - Physical attractiveness and the accumulation of social and human capital in
      adolescence and young adulthood: assets and distractions.
AB  - Beauty has a well-documented impact on labor market outcomes with both legal and
      policy implications. This monograph investigated whether this stratification is
      rooted in earlier developmental experiences. Specifically, we explored how high
      schools' dual roles as contexts of social relations and academic progress
      contributed to the long-term socioeconomic advantages of being physically
      attractive. Integrating theories from multiple disciplines, the conceptual model
      of this study contends that physically attractive youths' greater social
      integration and lesser social stigma help them accumulate psychosocial resources
      that support their academic achievement while also selecting them into social
      activities that distract from good grades. A mixed methods design, combining
      statistical analyses of the National Longitudinal Survey of Adolescent Health and
      qualitative analyses of a single high school, supported and expanded this model.
      The data revealed that the benefits of attractiveness flowed through greater
      social integration but were partially offset by social distractions, especially
      romantic/sexual partnerships and alcohol-related problems. Interview and
      ethnographic data further revealed that adolescents themselves understood how
      physical attractiveness could lead to favorable treatment by teachers and
      classmates while also enticing youth to emphasize socializing and dating, even
      when the latter took time from other activities (like studying) and marginalized
      some classmates. These patterns, in turn, predicted education, work, family, and
      mental health trajectories in young adulthood. The results of this
      interdisciplinary, theoretically grounded, mixed methods study suggest that
      adolescence may be a critical period in stratification by physical appearance and
      that the underlying developmental phenomena during this period are complex and
      often internally contradictory. The monograph concludes with discussion of
      theoretical and policy implications and recommendations for future developmental
      research.

PMID- 24329926
TI  - Biobehavioral profiles of arousal and social motivation in autism spectrum
      disorders.
AB  - BACKGROUND: Children with autism spectrum disorder (ASD) are impaired in social
      communication and interaction with peers, which may reflect diminished social
      motivation. Many children with ASD show enhanced stress when playing with other
      children. This study investigated social and stress profiles of children with ASD
      during play. METHODS: We utilized a peer interaction paradigm in a natural
      playground setting with 66 unmedicated, prepubertal, children aged 8-12 years [38
      with ASD, 28 with typical development (TD)]. Salivary cortisol was collected
      before and after a 20-min playground interaction that was divided into periods of
      free and solicited play facilitated by a confederate child. Statistical analyses
      included Wilcoxon rank-sum tests, mixed effects models, and Spearman correlations
      to assess the between-group differences in social and stress functioning,
      identify stress responders, and explore associations between variables,
      respectively. RESULTS: There were no differences between the groups during
      unsolicited free play; however, during solicited play by the confederate,
      significant differences emerged such that children with ASD engaged in fewer
      verbal interactions and more self-play than the TD group. Regarding physiological
      arousal, children with ASD as a group showed relatively higher cortisol in
      response to social play; however, there was a broad range of responses. Moreover,
      those with the highest cortisol levels engaged in less social communication.
      CONCLUSIONS: The social interaction of children with ASD can be facilitated by
      peer solicitation; however, it may be accompanied by increased stress. The
      children with ASD that have the highest level of cortisol show less social
      motivation; yet, it is unclear if it reflects an underlying state of heightened
      arousal or enhanced reactivity to social engagement, or both.

PMID- 24329928
TI  - Tumour stage and preoperative chemoradiotherapy influence the lymph node yield in
      stages I-III rectal cancer: results from a prospective nationwide cohort study.
AB  - AIM: The study aimed to determine whether the lymph node yield (LNY) in rectal
      cancer is influenced by patient-related and histopathological factors and the use
      of preoperative chemoradiotherapy (CRT). METHOD: An analysis was carried out of
      the LNY in a nationwide Danish cohort of 7950 patients, treated by curative
      resection of Stage I-III rectal cancer during the period 2001-2011. The impact of
      year of diagnosis, age, gender, pathological stage of the tumour (pT-stage) and
      preoperative CRT on LNY was analysed. RESULTS: Twenty-nine per cent of the
      patients received preoperative CRT. The median LNY was 13 [interquartile range
      (IQR): 8-19]. A total of 43.4% of the patients had an LNY of < 12. The median LNY
      increased from 8 (IQR: 5-12) to 20 (IQR: 13-28) LNs over the years of the study
      period (P < 0.0001). Gender and body mass index (BMI) had no impact on the median
      LNY. Age had a minor impact, with a range of 12 (IQR: 8-18) to 13 (IQR: 9-20) (P
      < 0.0001). The LNY ranged from 9 (IQR: 6-14) to 16 (IQR: 10-26), according to pT
      stage (pT0-pT4) (P < 0.0001). Median LNY, according to preoperative CRT or no
      preoperative CRT, was 10 (IQR: 6-16) and 14 (IQR: 8-18), respectively (P <
      0.0001). The percentages of patients with an LNY of < 12, according to
      preoperative CRT or no preoperative CRT, were 58.7% and 37.1%, respectively (P <
      0.0001). CONCLUSION: An increase in the LNY over the period of the study was
      observed, probably reflecting improved quality of surgery and histopathology. A
      minor significant reduction of LNY was found with increasing age of the patient.
      LNY was significantly related to pT-stage and to the use of preoperative
      chemoradiotherapy. For these reasons the minimum harvest of 12 LNs as a surrogate
      marker for the oncological quality of surgery should be questioned.

PMID- 24329927
TI  - Bortezomib therapy-related lung disease in Japanese patients with multiple
      myeloma: incidence, mortality and clinical characterization.
AB  - Because of the potentially high mortality rate (6.5%) associated with bortezomib
      induced lung disease (BILD) in Japanese patients with relapsed or refractory
      multiple myeloma, we evaluated the incidence, mortality and clinical features of
      BILD in a Japanese population. This study was conducted under the Risk
      Minimization Action Plan (RMAP), which was collaboratively developed by the
      pharmaceutical industry and public health authority. The RMAP consisted of an
      intensive dissemination of risk information and a recommended countermeasure to
      health-care professionals. All patients treated with bortezomib were
      consecutively registered in the study within 1 year and monitored for emerging
      BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of
      whom had fatal cases. The median time to BILD onset from the first bortezomib
      dose was 14.5 days, and most of the patients responded well to corticosteroid
      therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed
      that the types with capillary leak syndrome and hypoxia without infiltrative
      shadows were uniquely and frequently observed in patients with BILD compared with
      those with conditions associated with other molecular-targeted anticancer drugs.
      The incidence rate of BILD in Japan remains high compared with that reported in
      other countries, but the incidence and mortality rates are lower than expected
      before the introduction of bortezomib in Japan. This study describes the
      radiographic pattern and clinical characterization of BILD in the Japanese
      population. The RMAP seemed clinically effective in minimizing the BILD risk
      among our Japanese population. 

PMID- 24329929
TI  - Periodontal effects of 0.25% sodium hypochlorite twice-weekly oral rinse. A pilot
      study.
AB  - BACKGROUND AND OBJECTIVE: The study aimed to evaluate the effect of 0.25% sodium
      hypochlorite twice-weekly oral rinse on plaque and gingivitis in patients with
      minimally treated periodontitis. MATERIAL AND METHODS: The study included 30
      patients with periodontitis, it lasted 3 mo, and it was performed as a
      randomized, controlled, single-blinded, clinical trial in parallel groups.
      Fifteen patients rinsed for 30 s with 15 mL of a fresh solution of 0.25% sodium
      hypochlorite (test) and 15 patients rinsed with 15 mL of water (control).
      Clorox((r)) regular bleach was the source of the sodium hypochlorite. At baseline
      and at 2 wk, the study patients received professional subgingival irrigation for
      5 min with either 0.25% sodium hypochlorite or water, but no subgingival or
      supragingival scaling. The presence or absence of supragingival plaque on facial
      and lingual surfaces was determined by visual inspection; each tooth was dried
      with air and mouth mirror rotation was used to provide light reflection to
      identify plaque on smooth surfaces and at the tooth line angles. Gingival
      bleeding within 30 s after probing to full pocket depth was assessed in six sites
      of each tooth. Adverse events were evaluated by questionnaire and visual
      examination. RESULTS: All 30 patients in the study completed the baseline and the
      2 wk parts of the study and a subset of 12 participants completed the 3 mo part
      of the study. The sodium hypochlorite rinse group and the water rinse group,
      respectively, showed increases from baseline to 3 mo of 94% and 29% (3.2-fold
      difference) in plaque-free facial surfaces, of 195% and 30% (6.5-fold difference)
      in plaque-free lingual surfaces, and of 421% and 29% (14.5-fold difference) in
      number of teeth with no bleeding on probing. The differences in clinical
      improvement between the sodium hypochlorite rinse group and the water rinse group
      were statistically significant. No adverse events were identified in any of the
      study patients, except for minor complaints about the taste of bleach.
      CONCLUSION: A twice-weekly oral rinse with 0.25% sodium hypochlorite produced
      marked decreases in dental plaque level and bleeding on probing and may
      constitute a promising new approach to the management of periodontal disease.
      Long-term controlled studies on the effectiveness of sodium hypochlorite oral
      rinse are needed and encouraged.

PMID- 24329930
TI  - Adverse childhood experiences: towards a clear conceptual meaning.
AB  - AIM: To report an analysis of the concept of adverse childhood experiences.
      BACKGROUND: Adverse childhood experiences have been associated with negative
      physical and psychological health outcomes, but this phenomenon lacks the clear,
      consistent meaning necessary for use in nursing research, theory development and
      practice. DESIGN: Concept clarification. DATA SOURCES: The literature search was
      not limited a priori by date and included publications with abstracts in English
      from PubMed, CINAHL, PsychINFO and Social Abstracts. The search retrieved 128
      articles published from 1970-2013. The search term 'adverse childhood
      experiences' was used, with similar terms permitted. A snowball approach was used
      to expand the search to relevant literature. METHODS: The articles were read and
      analysed following Norris's five steps for concept clarification to refine,
      elucidate and operationally define the concept and the context in which it
      occurred. RESULTS: Adverse childhood experiences were defined operationally as
      childhood events, varying in severity and often chronic, occurring in a child's
      family or social environment that cause harm or distress, thereby disrupting the
      child's physical or psychological health and development. CONCLUSION: This
      concept clarification should raise awareness and understanding of the diverse
      nature and shared characteristics of adverse childhood experiences that are
      believed to influence the health of individuals as they age. This clarified
      concept will help expand research on health consequences of adverse childhood
      experiences and interventions to improve health. We recommend promoting a model
      of primary care that pays attention to the social and familial influences on the
      health of individuals worldwide.

PMID- 24329931
TI  - Respiratory allergen from house dust mite is present in human milk and primes for
      allergic sensitization in a mouse model of asthma.
AB  - There is an urgent need to identify environmental risk and protective factors in
      early life for the prevention of allergy. Our study demonstrates the presence of
      respiratory allergen from house dust mite, Der p 1, in human breast milk. Der p 1
      in milk is immunoreactive, present in similar amounts as dietary egg antigen, and
      can be found in breast milk from diverse regions of the world. In a mouse model
      of asthma, oral exposure to Der p through breast milk strongly promotes
      sensitization rather than protect the progeny as we reported with egg antigen.
      These data highlight that antigen administration to the neonate through the oral
      route may contribute to child allergic sensitization and have important
      implications for the design of studies assessing early oral antigen exposure for
      allergic disease prevention. The up-to-now unknown worldwide presence of
      respiratory allergen in maternal milk allows new interpretation and design of
      environmental control epidemiological studies for allergic disease prevention. 

PMID- 24329932
TI  - Chemistry, stability and bioavailability of resveratrol.
AB  - Resveratrol is a bioactive polyphenol found in many vegetables. It is well known
      for its multiple pharmacological activities, such as anti-inflammatory,
      antioxidant, antimicrobial, anticancer, neuroprotective and cardioprotective
      effects. In vitro evidence of resveratrol efficacy is widespread, however, many
      concerns regarding its effectiveness in vivo arise from its poor stability in
      vitro and bioavailability following oral ingestion. This review focuses on the in
      vitro stability, with special focus on the photochemical stability of
      resveratrol, and on the therapeutic perspectives of this molecule due to its low
      bioavailability. 

PMID- 24329934
TI  - Cultural transmission and the evolution of human behaviour: a general approach
      based on the Price equation.
AB  - Transmitted culture can be viewed as an inheritance system somewhat independent
      of genes that is subject to processes of descent with modification in its own
      right. Although many authors have conceptualized cultural change as a Darwinian
      process, there is no generally agreed formal framework for defining key concepts
      such as natural selection, fitness, relatedness and altruism for the cultural
      case. Here, we present and explore such a framework using the Price equation.
      Assuming an isolated, independently measurable culturally transmitted trait, we
      show that cultural natural selection maximizes cultural fitness, a distinct
      quantity from genetic fitness, and also that cultural relatedness and cultural
      altruism are not reducible to or necessarily related to their genetic
      counterparts. We show that antagonistic coevolution will occur between genes and
      culture whenever cultural fitness is not perfectly aligned with genetic fitness,
      as genetic selection will shape psychological mechanisms to avoid susceptibility
      to cultural traits that bear a genetic fitness cost. We discuss the difficulties
      with conceptualizing cultural change using the framework of evolutionary theory,
      the degree to which cultural evolution is autonomous from genetic evolution, and
      the extent to which cultural change should be seen as a Darwinian process. We
      argue that the nonselection components of evolutionary change are much more
      important for culture than for genes, and that this and other important
      differences from the genetic case mean that different approaches and emphases are
      needed for cultural than genetic processes. 

PMID- 24329935
TI  - Respiratory viral infections in pregnant women with asthma are associated with
      wheezing in the first 12 months of life.
AB  - BACKGROUND: There are few studies investigating the relationship between
      respiratory viral infection in pregnancy and asthma in the offspring, and none
      among mothers with asthma. Infants of mothers with asthma are more likely to
      wheeze and have a higher risk of developing asthma than infants of non-asthmatic
      mothers. METHODS: A prospective cohort study of viral infection in pregnancy was
      conducted between 2007 and 2009, and a subgroup of infants of mothers with asthma
      was followed up at 6 and 12 months of age. During common colds, nasal and throat
      swabs were collected from mothers and respiratory viruses detected by polymerase
      chain reaction. Respiratory health of infants was assessed by parent-completed
      questionnaire. RESULTS: Twelve-month-old infants whose mothers had confirmed
      viral infections in pregnancy (n = 26) reported more frequent wheeze (40% had 4
      12 wheeze attacks compared with 0%), sleep disturbed by wheeze (1 night per week
      or more in 60% vs. 11%), beta agonist treatment for wheeze (27% vs. 0%),
      prolonged colds (2 wk or longer 31% vs. 0%), more eczema (40% vs. 6.3%), and
      parent-perceived asthma (32% vs. 0%), compared with infants whose mothers had
      common colds without laboratory-confirmed viral infection (n = 16). CONCLUSIONS:
      This study demonstrates a relationship between maternal respiratory viral
      infection in pregnancy and wheezing illness in infants of mothers with asthma.
      Viral infections are the most common cause of asthma exacerbations in pregnancy,
      and infants of asthmatic mothers are at increased risk of asthma themselves.
      Further research is needed to elucidate the mechanisms involved.

PMID- 24329933
TI  - Neurosystems: brain rhythms and cognitive processing.
AB  - Neuronal rhythms are ubiquitous features of brain dynamics, and are highly
      correlated with cognitive processing. However, the relationship between the
      physiological mechanisms producing these rhythms and the functions associated
      with the rhythms remains mysterious. This article investigates the contributions
      of rhythms to basic cognitive computations (such as filtering signals by
      coherence and/or frequency) and to major cognitive functions (such as attention
      and multi-modal coordination). We offer support to the premise that the
      physiology underlying brain rhythms plays an essential role in how these rhythms
      facilitate some cognitive operations. 

PMID- 24329936
TI  - Striatum and insula dysfunction during reinforcement learning differentiates
      abstinent and relapsed methamphetamine-dependent individuals.
AB  - BACKGROUND AND AIMS: Individuals with methamphetamine dependence (MD) exhibit
      dysfunction in brain regions involved in goal maintenance and reward processing
      when compared with healthy individuals. We examined whether these characteristics
      also reflect relapse vulnerability within a sample of MD patients. DESIGN:
      Longitudinal, with functional magnetic resonance imaging (fMRI) and clinical
      interview data collected at baseline and relapse status collected at 1-year
      follow-up interview. SETTING: Keck Imaging Center, University of California San
      Diego, USA. PARTICIPANTS: MD patients (n = 60) enrolled into an in-patient drug
      treatment program at baseline. MD participants remaining abstinent at 1-year
      follow-up (abstinent MD group; n = 42) were compared with MD participants who
      relapsed within this period (relapsed MD group; n = 18). MEASUREMENTS: Behavioral
      and neural responses to a reinforcement learning (paper-scissors-rock) paradigm
      recorded during an fMRI session at time of treatment. FINDINGS: The relapsed MD
      group exhibited greater bilateral inferior frontal gyrus (IFG) and right striatal
      activation than the abstinent MD group during the learning of reward
      contingencies (Cohen's d range: 0.60-0.83). In contrast, the relapsed MD group
      displayed lower bilateral striatum, bilateral insula, left IFG and left anterior
      cingulate activation than the abstinent MD group (Cohen's d range: 0.90-1.23) in
      response to winning, tying and losing feedback. CONCLUSIONS: Methamphetamine
      dependent individuals who achieve abstinence and then relapse show greater
      inferior frontal gyrus activation during learning, and relatively attenuated
      striatal, insular and frontal activation in response to feedback, compared with
      methamphetamine-dependent people who remain abstinent.

PMID- 24329937
TI  - A tool for selecting patients with a high probability of sustained virological
      response to peginterferon alfa-2a (40kD)/ribavirin.
AB  - BACKGROUND & AIMS: Pretreatment identification of patients likely to achieve a
      sustained virological response (SVR) with peginterferon alfa-2a/ribavirin would
      be useful for individualizing treatment choices. The aim of this analysis was to
      devise a simple scoring system to identify patients with high probability of
      achieving an SVR with peginterferon alfa-2a/ribavirin. METHODS: Using data from
      2109 Caucasian treatment-naive hepatitis C virus (HCV) genotype 1 mono-infected
      patients from the PROPHESYS cohorts, the relationship between favourable baseline
      characteristics and SVR was explored using generalized additive model analysis,
      and a scoring system was devised to predict SVR. RESULTS: Points were assigned
      for: age (years) (<=35: 2; >35, <=45: 1; >45: 0); body mass index (kg/m(2))
      (<=20: 2; >20, <=22: 1; >22: 0); HCV RNA (IU/ml) (<=100,000: 3; >100,000-400,000:
      2; >400,000-800,000: 1; >800,000: 0); platelets (>150 *10(9)/l: 1; <=150
      *10(9)/l: 0); alanine aminotransferase [*upper limit of normal (ULN)] (>3: 1;
      <=3: 0); serum aspartate aminotransferase (*ULN) (<=1: 1; >1: 0). 1029, 698 and
      382 patients had scores of 0-2, 3-4 and >=5, respectively, among whom SVR rates
      were 35.0, 54.9 and 76.7%. SVR in patients with scores >=5 and undetectable HCV
      RNA by week 4 was 86.7%. The score was tested against two databases of patients
      who received peginterferon alfa-2a/ribavirin in other clinical trials; similar
      high SVR rates in patients with scores >=5 were reported. CONCLUSIONS: The
      scoring system can reliably identify treatment-naive HCV genotype 1 mono-infected
      Caucasian patients who have a high probability of achieving an SVR with
      peginterferon alfa-2a/ribavirin and will be particularly useful where protease
      inhibitors are not readily available.

PMID- 24329938
TI  - Systematic reviews and meta-analyses in infectious diseases: topics that merit
      special attention.
AB  - As in other disciplines in medicine, systematic reviews (SR) and meta-analyses
      (MA) in infectious diseases are an important aid to clinical decision-making. In
      the present article we review features important to SRs in infectious diseases
      that should be addressed in most SRs and MAs. We stress the need to include in
      the SR analysis all patients that were randomized; and all studies that were
      performed. Authors of SRs should choose one main outcome that matters to
      patients, and base their conclusions mainly on this outcome. Resistance as an
      outcome is a topic that should be addressed in all SRs of antibiotic treatment.
      Ethical aspects and especially patients' safety should be addressed in SRs. 

PMID- 24329939
TI  - DropArrayTM, a wall-less 96-well plate for uptake and immunofluorescence
      microscopy, confirms CD22 recycles.
AB  - CD22 is a cell surface glycoprotein restricted to normal and malignant B-cells
      and is the target of several anti-CD22 antibody-based cancer therapies. For
      therapeutic antibody-payload conjugates, it is important to understand the
      subcellular trafficking of anti-CD22 antibodies to optimize antibody and/or
      linker-drug properties to maximize antitumor efficacy. It is agreed that anti
      CD22 antibodies rapidly internalize, but controversial whether they recycle or
      are degraded in lysosomes, and it is unclear if trafficking is antibody or cell
      type dependent. No studies examined anti-CD22 trafficking to either pathway in B
      cells over time by dual immunofluorescence microscopy, likely partly because
      multiple samples of suspension cells are tedious to stain. We overcame this by
      using DropArrayTM, a novel wall-less 96-well plate technology allowing rapid
      simultaneous staining of suspension or adherent cells in small (10-20 MUL)
      volumes. We examined the time-course of trafficking of five different anti-CD22
      antibodies in eight B-cell lines representing four B-cell cancer types and show
      that in all cases antibodies internalize within 5 min and recycle, with only
      small amounts eventually trafficking to lysosomes. CD22 also localizes to
      recycling endosomes at steady state in the absence of antibody. Our data may help
      explain the differential efficacies of anti-CD22 antibodies conjugated to
      different therapeutic payloads.

PMID- 24329940
TI  - The use of plant cell wall-degrading enzymes from newly isolated Penicillium
      ochrochloron Biourge for viscosity reduction in ethanol production with fresh
      sweet potato tubers as feedstock.
AB  - Penicillium ochrochloron Biourge, which was isolated from rotten sweet potato,
      can produce plant cell wall-degrading enzymes (PCWDEs) with high viscosity
      reducing capability for ethanol production using fresh sweet potato tubers as
      feedstock. The enzyme preparation was characterized by a broad enzyme spectrum
      including 13 kinds of enzymes with the activity to hydrolyze cellulose,
      hemicellulose, pectin, starch, and protein. The maximum viscosity-reducing
      capability was observed when the enzyme preparation was obtained after 5 days of
      fermentation using 20 g/L corncob as a sole carbon source, 4.5 g/L NH4 NO3 as a
      sole nitrogen source, and an initial medium pH of 6.5. The sweet potato mash
      treated with the enzyme preparation exhibited much higher fermentation efficiency
      (92.58%) compared with commercial cellulase (88.06%) and control (83.5%). The
      enzyme production was then scaled up to 0.5, 5, and 100 L, and the viscosity
      reducing rates were found to be 85%, 90%, and 91%, respectively. Thus, P.
      ochrochloron Biourge displays potential viscosity-reducing capability for ethanol
      production. 

PMID- 24329941
TI  - The impact of accident attention, ideology, and environmentalism on American
      attitudes toward nuclear energy.
AB  - This study involves the analysis of three waves of survey data about nuclear
      energy using a probability-based online panel of respondents in the United
      States. Survey waves included an initial baseline survey conducted in early 2010,
      a follow-up survey conducted in 2010 following the Deepwater Horizon oil spill in
      the Gulf of Mexico, and an additional follow-up conducted just after the 2011
      Fukushima, Japan, nuclear accident. The central goal is to assess the degree to
      which changes in public views following an accident are contingent on individual
      attention and respondent predispositions. Such results would provide real-world
      evidence of motivated reasoning. The primary analysis focuses on the impact of
      Fukushima and how the impact of individual attention to energy issues is
      moderated by both environmental views and political ideology over time. The
      analysis uses both mean comparisons and multivariate statistics to test key
      relationships. Additional variables common in the study of emerging technologies
      are included in the analysis, including demographics, risk and benefit
      perceptions, and views about the fairness of decisionmakers in both government
      and the private sector. 

PMID- 24329942
TI  - Resection margins in pancreatic cancer: are we entering a new era?

PMID- 24329943
TI  - The effect of educational intervention on prevention of postpartum depression: an
      application of health locus of control.
AB  - AIMS AND OBJECTIVES: To assess the effectiveness of application of health locus
      of control in pregnant women for prevention of postpartum depression in Iran.
      BACKGROUND: Nearly 10-15% of women suffer postnatal depression by the end of the
      second week after delivery, which creates problems in caring for the child that
      may affect child's future learning and concentration. DESIGN: Pre-post
      experimental design. METHODS: Two hundred and thirty volunteer women were
      randomly divided into experimental and control groups. The data collection tools
      included a demographic questionnaire, the Multidimensional Health Locus of
      Control Scale and the Edinburg Depression Scale. Based on the associations found
      in the pretest, intervention programme was planned and carried out in the focused
      group discussion method. Data were collected after the end of scheduled sessions,
      immediately and one month later. The data were analysed with SPSS-16 using
      statistical methods including anova, chi-square test, Student's t-test and paired
      t-test. RESULTS: Chance health locus of control significantly reduced and
      internal health locus of control significantly increased, immediately after
      intervention. Also, a month after intervention, a significant difference was
      observed between the two groups in reducing postpartum depression. CONCLUSIONS:
      The planned participatory intervention led to empowerment and increased awareness
      and internalisation of health control beliefs and less tendency towards external
      health control beliefs, especially chance, improvement in general health leading
      to improved psychological health for prevention of postpartum depression in
      mothers. RELEVANCE TO CLINICAL PRACTICE: Clinicians might assess chance and
      internal health locus of control to identify the women at risk of developing
      depression during their pregnancy and to develop prevention and treatment plans.

PMID- 24329944
TI  - Short duration of lamivudine for the prevention of hepatitis B virus transmission
      in pregnancy: lack of potency and selection of resistance mutations.
AB  - This study sought to assess the antiviral efficacy of lamivudine (LMV)
      administered during third trimester to reduce maternal viraemia and to identify
      the emergence of LMV resistance. A prospective observational analysis was
      performed on 26 mothers with high viral load (>107 IU/mL). Twenty-one women
      received LMV (treated group) for an average of 53 days (range 22-88 days), and
      the remaining five formed the untreated control group. Serum samples from two
      time points were used to measure HBV DNA levels and antiviral drug resistance.
      The LMV-treated women achieved a median HBV DNA reduction of 2.6-log10 IU/mL.
      Although end-of-treatment (EOT) HBV DNA in four (18%) LMV-treated women remained
      at >10(7) IU/mL (+/- 0.5 log IU/mL), no mother-to-baby transmission was observed.
      In contrast, a baby from the untreated mother was HBsAg positive at 9 months
      postpartum. Four technologies were used for drug resistance testing. Only ultra
      deep pyrosequencing (UDPS) was sufficiently sensitive to detect minor viral
      variants down to <1%. UDPS showed that LMV therapy resulted in increased viral
      quasispecies diversity and positive selection of HBV variants with reverse
      transcriptase amino acid substitutions at sites associated with primary LMV
      resistance (rtM204I/V and rtA181T) in four (19%) women. These viral variants were
      detected mostly at low frequencies (0.63-5.92%) at EOT, but one LMV-treated
      mother had an rtA181T variant that increased from 2.2% pretherapy to 25.59% at
      EOT. This mother was also infected with the vaccine escape variant (sG145R),
      which was inhibited by LMV treatment. LMV therapy during late pregnancy only
      reduced maternal viraemia moderately, and drug-resistant viral variants emerged.

PMID- 24329945
TI  - Irritable bowel syndrome subtypes: constipation, diarrhea...and mixed bowel
      pattern: tertium datur.
AB  - The study by Su et al. published in this issue of NGM provides helpful insight
      into a relatively large, yet understudied, subgroup of IBS known as IBS with
      mixed bowel pattern (IBS-M). These investigators found among their 289 IBS
      subjects who underwent detailed assessment the IBS-M subtype to be particularly
      common. Interestingly, prior use of laxatives or antidiarrheal agents was found
      to potentially explain the mixed bowel pattern in approximately 30% of patients.
      These IBS-M patients tended to report more severe IBS symptoms. IBS-M patients
      had bowel symptoms more similar to IBS-D than IBS-C, particularly with regard to
      the rectal urgency. Hopefully many more studies will be forthcoming to further
      our understanding of IBS-M. 

PMID- 24329946
TI  - Intestinal microbiota influence the early postnatal development of the enteric
      nervous system.
AB  - BACKGROUND: Normal gastrointestinal function depends on an intact and coordinated
      enteric nervous system (ENS). While the ENS is formed during fetal life,
      plasticity persists in the postnatal period during which the gastrointestinal
      tract is colonized by bacteria. We tested the hypothesis that colonization of the
      bowel by intestinal microbiota influences the postnatal development of the ENS.
      METHODS: The development of the ENS was studied in whole mount preparations of
      duodenum, jejunum, and ileum of specific pathogen-free (SPF), germ-free (GF), and
      altered Schaedler flora (ASF) NIH Swiss mice at postnatal day 3 (P3). The
      frequency and amplitude of circular muscle contractions were measured in
      intestinal segments using spatiotemporal mapping of video recorded spontaneous
      contractile activity with and without exposure to lidocaine and N-nitro-L
      arginine (NOLA). KEY RESULTS: Immunolabeling with antibodies to PGP9.5 revealed
      significant abnormalities in the myenteric plexi of GF jejunum and ileum, but not
      duodenum, characterized by a decrease in nerve density, a decrease in the number
      of neurons per ganglion, and an increase in the proportion of myenteric nitrergic
      neurons. Frequency of amplitude of muscle contractions were significantly
      decreased in the jejunum and ileum of GF mice and were unaffected by exposure to
      lidocaine, while NOLA enhanced contractile frequency in the GF jejunum and ileum.
      CONCLUSIONS & INFERENCES: These findings suggest that early exposure to
      intestinal bacteria is essential for the postnatal development of the ENS in the
      mid to distal small intestine. Future studies are needed to investigate the
      mechanisms by which enteric microbiota interact with the developing ENS.

PMID- 24329947
TI  - Calcium responses in subserosal interstitial cells of the guinea-pig proximal
      colon.
AB  - BACKGROUND: In the subserosal layer between the longitudinal muscle layer and
      mesothelium, heterogeneous populations of interstitial cells are distributed. As
      the distribution of nerve elements in this layer is sparse as compared with the
      nerve plexus layer or tunica muscularis, there may be unique communication among
      subserosal interstitial cells (SSICs). This study aimed to explore functional
      properties of SSICs. METHODS: In subserosal preparations of the guinea-pig
      proximal colon, changes in intracellular Ca(2+) ([Ca(2+) ]i ) were visualized
      using Fluo-4 Ca(2+) imaging. Immunohistochemistry was also performed to identify
      the SSICs exhibiting Ca(2+) transients. KEY RESULTS: A majority of SSICs
      responded to adenosine triphosphate (ATP, 10 MUM) by increasing [Ca(2+) ]i , but
      remained quiescent during the application of acetylcholine (10 MUM). ATP-induced
      Ca(2+) responses were mimicked by adenosine 5'-diphosphate (10 MUM), MRS2365 (10
      nM) but not alpha, beta-methylene ATP (10 MUM) or uridine triphosphate (10 MUM),
      and could be reproduced in Ca(2+) -free solution, suggesting that ATP acts via
      P2Y receptors, most likely P2Y1 subtype, but not P2X receptors. Live staining of
      the same preparations after Ca(2+) imaging indicated the ATP-sensitive SSICs were
      not positive for c-Kit antibody, a specific marker for gastrointestinal
      interstitial cells of Cajal (ICC). Immunohistochemistry identified vimentin
      (mesenchymal cell marker)+/Kit- and SK3 (fibroblast-like cell (FLC) marker)+/Kit-
      cells that had a similar morphology to the ATP-sensitive SSICs in Ca(2+) imaging.
      CONCLUSIONS & INFERENCES: A majority of the SSICs in the guinea-pig proximal
      colon, presumably FLC, are capable of responding to ATP and thus may contribute
      to smooth muscle relaxation upon stimulation with ATP released from non-neuronal
      cells.

PMID- 24329949
TI  - Children's conceptions of physical events: explicit and tacit understanding of
      horizontal motion.
AB  - The conceptual understanding that children display when predicting physical
      events has been shown to be inferior to the understanding they display when
      recognizing whether events proceed naturally. This has often been attributed to
      differences between the explicit engagement with conceptual knowledge required
      for prediction and the tacit engagement that suffices for recognition, and
      contrasting theories have been formulated to characterize the differences.
      Focusing on a theory that emphasizes omission at the explicit level of conceptual
      elements that are tacitly understood, the paper reports two studies that attempt
      clarification. The studies are concerned with 6- to 10-year-old children's
      understanding of, respectively, the direction (141 children) and speed (132
      children) of motion in a horizontal direction. Using computer-presented billiards
      scenarios, the children predicted how balls would move (prediction task) and
      judged whether or not simulated motion was correct (recognition task). Results
      indicate that the conceptions underpinning prediction are sometimes interpretable
      as partial versions of the conceptions underpinning recognition, as the omission
      hypothesis would imply. However, there are also qualitative differences, which
      suggest partial dissociation between explicit and tacit understanding. It is
      suggested that a theoretical perspective that acknowledges this dissociation
      would provide the optimal framework for future research. 

PMID- 24329948
TI  - Rhizobial infection does not require cortical expression of upstream common
      symbiosis genes responsible for the induction of Ca(2+) spiking.
AB  - For the establishment of an effective root nodule symbiosis, a coordinated
      regulation of the infection processes between the epidermis and cortex is
      required. However, it remains unclear whether the symbiotic genes identified so
      far are involved in epidermal and/or cortical infection, e.g. epidermal and
      cortical infection thread formation or cortical cell division. To analyze the
      symbiotic gene requirements of the infection process, we have developed an
      epidermis-specific expression system (pEpi expression system) and examined the
      symbiotic genes NFR1, NFR5, NUP85, NUP133, CASTOR, POLLUX, CCaMK, CYCLOPS, NSP1
      and NSP2 for involvement in the infection process in the epidermis and cortex.
      Our study shows that expression of the upstream common symbiosis genes CASTOR,
      POLLUX, NUP85 and NUP133 in the epidermis is sufficient to induce formation of
      infection threads and cortical cell division, leading to the development of fully
      effective nodules. Our system also shows a requirement of CCaMK, CYCLOPS, NSP1
      and NSP2 for the entire nodulation process, and the different contributions of
      NFR1 and NFR5 to cortical infection thread formation. Based on these analyses
      using the pEpi expression system, we propose a functional model of symbiotic
      genes for epidermal and cortical infection. 

PMID- 24329950
TI  - Evaluation of trace elements, oxidant/antioxidant status, vitamin C and beta
      carotene in dogs with dermatophytosis.
AB  - The aim of the study was to determine zinc, copper and iron levels, erythrocyte
      oxidant/antioxidant status, vitamin C and beta-carotene in dogs with
      dermatophytosis. A total of 23 dogs with clinically established diagnosis of
      dermatophytosis by trichogram and positive fungal culture and six dogs as control
      were included in this study. On cultural examination 52.17% fungal isolates were
      found to be Microsporum canis, 30.43% were Trichophyton mentagrophytes and 17.39%
      were M. gypseum. In comparison to healthy control, the dogs with dermatophytosis
      had significantly lower levels of zinc (P < 0.01), copper (P < 0.05), beta
      carotene and vitamin C levels (P < 0.05) and activities of superoxide dismutase
      (SOD) (P < 0.05) and catalase (P < 0.01), whereas the iron (P < 0.05) and
      malondialdehyde (MDA) (P < 0.01) levels were significantly increased. On
      correlation analysis, SOD activity was observed to be positively correlated (P <
      0.05) with zinc and copper in both healthy and dermatophytosis affected dogs. In
      dermatophytosis affected dogs the MDA levels were negatively correlated (P <
      0.05) with iron, beta-carotene levels and the activities of antioxidant enzymes;
      SOD and catalase. Our results demonstrated that dermatophytosis in dogs is
      associated with significant alteration in oxidant/antioxidant balance and trace
      elements. It might be secondary consequence of dermatophytosis infection or
      contributing factor in its pathogenesis. 

PMID- 24329951
TI  - Development of formulations and processes to incorporate wax oleogels in ice
      cream.
AB  - The objective of this study was to investigate the influence of emulsifiers,
      waxes, fat concentration, and processing conditions on the application of wax
      oleogel to replace solid fat content and create optimal fat structure in ice
      cream. Ice creams with 10% or 15% fat were formulated with rice bran wax (RBW),
      candelilla wax (CDW), or carnauba wax (CBW) oleogels, containing 10% wax and 90%
      high-oleic sunflower oil. The ice creams were produced using batch or continuous
      freezing processes. Transmission electron microscopy (TEM) and cryo-scanning
      electron microscopy were used to evaluate the microstructure of ice cream and the
      ultrastructure of oleogel droplets in ice cream mixes. Among the wax oleogels,
      RBW oleogel had the ability to form and sustain structure in 15% fat ice creams
      when glycerol monooleate (GMO) was used as the emulsifier. TEM images revealed
      that the high degree of fat structuring observed in GMO samples was associated
      with the RBW crystal morphology within the fat droplet, which was characterized
      by the growth of crystals at the outer edge of the droplet. Continuous freezing
      improved fat structuring compared to batch freezing. RBW oleogels established
      better structure compared to CDW or CBW oleogels. These results demonstrate that
      RBW oleogel has the potential to develop fat structure in ice cream in the
      presence of GMO and sufficiently high concentrations of oleogel. 

PMID- 24329952
TI  - 75 years of IFT: food microbiology in JFS-1936 to present.

PMID- 24329954
TI  - Impact of the O2 concentrations on bacterial communities and quality of modified
      atmosphere packaged Pacific white shrimp (Litopenaeus vannamei).
AB  - The importance of spoilage-related bacteria in fresh Pacific white shrimp
      (Litopenaeus vannamei) under different modified atmospheres (MAs) at 4  degrees C
      and the effect of O2 were demonstrated in the current study. The changes of
      bacterial communities in MA-packed shrimp during cold storage were studied by a
      combined method of plate counts with isolation and identification. Three gas
      mixtures were applied: 80% CO2 /5% O2 /15% N2, 80% CO2 /10% O2 /10% N2 and 80%
      CO2 /20% O2, and unsealed packages of shrimp were used as the control. In
      addition, the TVB-N, pH, whiteness index, and sensory scores were also determined
      to evaluate the quality changes of shrimp. MA packaging effectively inhibited the
      increase of total psychrotrophic bacteria counts and H2 S-producing bacteria
      counts by about 1.7 and 2.1 log cycles, respectively. The growth of Gram-negative
      spoilage bacteria in shrimp, including Shewanella spp., Aeromonas spp., and
      Pseudomonas spp., was inhibited by MA packaging, but the growth rate of Gram
      positive bacteria such as lactic acid bacteria (LAB) and Brochothrix spp. were
      less affected by MA as effectively as Gram-negative bacteria. In comparison with
      the MA-packaged samples, the counts of H2 S producers in shrimp under a CO2 
      enriched atmosphere with 20% O2 were slightly lower than the count in samples
      under an atmosphere with 5% O2 . However, MA with 20% O2 led to higher
      concentrations of TVB-N, and lower whiteness values and sensory scores. The shelf
      life of shrimp under 80% CO2 /10% O2 /10% N2 has been prolonged by > 6 d in
      comparison with the control according to the sensory scores.

PMID- 24329955
TI  - Isolation and detection of extended spectrum beta-lactamase (ESBL)-producing
      enterobacteriaceae from meat using chromogenic agars and isothermal loop-mediated
      amplification (LAMP) assays.
AB  - The aim of this work was to develop a molecular method using loop-mediated
      isothermal amplification (LAMP) for detection of extended spectrum beta-lactamase
      (ESBL)-producing Enterobacteriaceae from meat, and to compare it with different
      isolation agars and microarrays. LAMP assays were developed for CTX-M groups 1,
      2, and 9 and OXA-10-like genes. Chicken, lamb, beef, pork, and turkey samples
      were spiked with 10, 100, and 1,000 cfu/gram using 8 strains of ESBL-producing
      Enterobacteriaceae (CTX-M sequence types 1, 2, 3, 14, 15, OXA-11, SHV-2, TEM-52)
      +/- a mix of competitor organisms. Samples were enriched overnight in buffered
      peptone water (BPW) +/- antibacterials before plating to CHROMagar CTX, OXOID
      ESBL Brilliance agar, and MacConkey agar with 1 mg/L cefotaxime. Selected BPW
      broths were also tested using LAMP assays, microarrays and using cefpodoxime
      discs on agar. For isolation/detection of ESBL producers from beef, pork, lamb,
      and turkey spiked with 10 or 100 cfu/gram ESBL (natural flora only), all agars
      and the LAMP assays showed 100% sensitivity and specificity for ESBL spike
      strains. For chicken samples, both LAMP and chromogenic agars showed improved
      sensitivity and specificity for isolation of ESBLs compared with MacConkey agar,
      particularly with competitor bacteria added. In comparison, the cefpodoxime disc
      method and microarray showed reduced sensitivity. 

PMID- 24329956
TI  - Synthesis and characterization of nano-encapsulated black pepper oleoresin using
      hydroxypropyl beta-cyclodextrin for antioxidant and antimicrobial applications.
AB  - Previous studies have reported antimicrobial and antioxidant activity of black
      pepper oleoresin which is associated to its phenolic compounds and piperine. The
      ability of cyclodextrins to form an inclusion complex with a guest molecule could
      improve black pepper oleoresin application, bioavailability, and stability in
      foods. Hydroxypropyl beta-cyclodextrin (HPBCD) inclusion complex with black
      pepper olereosin were synthesized using the kneading method and characterized for
      its physico-chemical properties and its antioxidant and antimicrobial activities.
      Inclusion complex size was 103.9 +/- 7.6 nm and indicated to be a polydisperse
      system. The entrapment efficiency was 78.3 +/- 3.6%, which suggests that other
      constituents in black pepper oleoresin have higher affinities for HPBCD than
      piperine (major compound in black pepper oleoresin). Thermograms showed the
      disappearance of oxidation peaks of black pepper oleoresin, proving complex
      formation with HPBCD. Phase solubility results indicated 1:1 stoichiometric
      inclusion complex formation and an increase of black pepper oleoresin aqueous
      solubility with HPBCD concentration. Nano-encapsulation with HPBCD did not affect
      (P > 0.05) total phenolic content; however, it enhanced (P < 0.05) black pepper
      oleoresin antioxidant activity. Black pepper oleoresin and its inclusion complex
      were analyzed for their antimicrobial activity against Escherichia coli K12 and
      Salmonella enterica serovar Typhimurium LT2. Both free and encapsulated black
      pepper oleoresin effectively inhibited bacterial growth within the concentration
      range tested. Black pepper oleoresin encapsulated in HPBCD was able to inhibit
      Salmonella at lower (P < 0.05) concentrations than its corresponding free
      extract. Therefore, black pepper oleoresin-HPBCD nanocapsules could have
      important applications in the food industry as antimicrobial and antioxidant
      system. 

PMID- 24329957
TI  - Investigating flavonoids as molecular templates for the design of small-molecule
      inhibitors of cell signaling.
AB  - Epidemiological and clinical trials reveal compelling evidence for the ability of
      dietary flavonoids to lower cardiovascular disease risk. The mechanisms of action
      of these polyphenolic compounds are diverse, and of particular interest is their
      ability to function as protein and lipid kinase inhibitors. We have previously
      described structure-activity studies that reinforce the possibility for using
      flavonoid structures as templates for drug design. In the present study, we aim
      to begin constructing rational screening strategies for exploiting these
      compounds as templates for the design of clinically relevant, antiplatelet
      agents. We used the platelet as a model system to dissect the structural
      influence of flavonoids, stilbenes, anthocyanidins, and phenolic acids on
      inhibition of cell signaling and function. Functional groups identified as
      relevant for potent inhibition of platelet function included at least 2 benzene
      rings, a hydroxylated B ring, a planar C ring, a C ring ketone group, and a C-2
      positioned B ring. Hydroxylation of the B ring with either a catechol group or a
      single C-4' hydroxyl may be required for efficient inhibition of collagen
      stimulated tyrosine phosphorylated proteins of 125 to 130 kDa, but may not be
      necessary for that of phosphotyrosine proteins at approximately 29 kDa. The
      removal of the C ring C-3 hydroxyl together with a hydroxylated B ring (apigenin)
      may confer selectivity for 37 to 38 kDa phosphotyrosine proteins. We conclude
      that this study may form the basis for construction of maps of flavonoid
      inhibitory activity on kinase targets that may allow a multitargeted therapeutic
      approach with analogue counterparts and parent compounds. 

PMID- 24329958
TI  - Detection of endogenous cortisol in equine tears and blood at rest and after
      simulated stress.
AB  - OBJECTIVE: To determine whether cortisol is present in equine tears at rest and
      during simulated stress and compare tear cortisol to serum free and total
      cortisol. MATERIALS AND METHODS: Fourteen healthy adult horses were included.
      Paired tear total cortisol and serum total and free cortisol concentrations were
      measured with ELISA, chemiluminescent immunoassay, and ultrafiltration
      methodology, respectively, in 10 horses at rest once daily for five consecutive
      days. In an additional four horses, paired tear and serum samples were collected
      for cortisol measurement before and after adrenocorticotropic hormone (ACTH)
      stimulation (cosyntropin, 1 MUg/kg IV). RESULTS: Cortisol was detectable in
      equine tears at rest. Following ACTH stimulation, tear cortisol increased
      significantly from baseline at 60-120 min (P <= 0.001). Serum total and free
      cortisol also increased significantly at 30-180 min after ACTH stimulation (P <=
      0.001). Both serum and tear cortisol returned to baseline concentrations by 360
      min. Changes in tear cortisol were similarly associated with changes in serum
      total and free cortisol, although high tear cortisol concentrations suggest a
      portion of tear cortisol may be protein-bound. DISCUSSION: Cortisol is present in
      equine tears and increases in concert with serum cortisol following ACTH
      stimulation. Further study is needed to determine whether endogenous cortisol in
      tears contributes to ocular pathology.

PMID- 24329959
TI  - Fully automated dual-color dual-hapten silver in situ hybridization staining for
      MYC amplification: a diagnostic tool for discriminating secondary angiosarcoma.
AB  - BACKGROUND: MYC amplification occurs in post-radiation and chronic lymphedema
      associated secondary angiosarcoma and some primary angiosarcomas. In this study,
      we tested the ability of automated dual-color dual-hapten in situ hybridization
      (DISH) staining to discriminate secondary angiosarcoma from radiation-associated
      atypical vascular lesions (AVL), and to correlate with fluorescence in situ
      hybridization (FISH) for MYC amplification. METHODS: Cases of secondary
      angiosarcoma, including 11 biopsies and 3 excisions from 11 patients, and 5 AVL
      biopsies from 5 patients, were examined by FISH and DISH. DISH staining was
      performed using the Dual Color Open Probe software on a Ventana Benchmark XT
      automated slide stainer. Metallic black silver (MYC) and reference CHR8 red
      signals were qualitatively and semi-quantitatively enumerated for tumor nuclei.
      Small and large clusters of silver signals were recorded as 6 or 12 signals,
      respectively. MYC amplification was defined as MYC/CHR8 ratio >2.0. RESULTS:
      Where tissue was available for both DISH and FISH, all secondary angiosarcoma
      cases showed MYC amplification (11/11 = 100%) by both DISH and FISH. All AVL were
      negative for MYC amplification by both techniques (0/5 = 0%). CONCLUSION: In the
      current cohort, use of DISH identified all MYC amplified cases, and distinguished
      secondary angiosarcoma from AVL. DISH staining may be useful in distinguishing
      secondary angiosarcoma from AVL in challenging cases.

PMID- 24329960
TI  - Determination of thromboelastographic responsiveness in stored single-donor
      platelet concentrates.
AB  - BACKGROUND: Thromboelastography (TEG) is widely used in hospitals but less
      commonly in blood banks for evaluation of platelet (PLT) concentrates (PCs). A
      TEG-PC assay for testing fresh or stored PLTs must reflect the quality of the
      PLTs. The added value could be measurement of donor-dependent PLT quality. STUDY
      DESIGN AND METHODS: Whole blood (WB) normal values were generated from 100
      donors, using standard tests. Nineteen single-donor PCs were evaluated with a TEG
      PC assay, using Octaplas as microparticle-free diluent and kaolin or collagen as
      activator, stored up to 12 days, and also sampled for additional in vitro tests.
      RESULTS: WB values showed larger reaction rates (R- and K-times, angle) compared
      to the reference values and almost similar maximum amplitude (MA). PCs showed
      usual storage lesion and TEG-PC results showed significant decreasing R- and K
      times and increasing angle. Mean MA values remained constant but individual
      measurements were affected by clot retraction. TEG tracings of two PCs with good
      quality on Day 12 showed weak to strong clot retraction, while two PCs with poor
      quality showed moderate clot retraction on Day 1, no clot retraction on Days 5 to
      12, and a decreased MA on Day 12. Clot strength (MA) and especially clot
      retraction represent possibly donor-specific effects. CONCLUSION: A TEG-PC assay
      has been developed that is sensitive to storage effects. The assay has the
      potential to be helpful in selection of PLT donors but needs improvement to be
      more sensitive, reproducible, and distinctive to determine whose PLTs store
      poorly and whose store well.

PMID- 24329961
TI  - The diagnosis of food allergy: a systematic review and meta-analysis.
AB  - BACKGROUND: We investigated the accuracy of tests used to diagnose food allergy.
      METHODS: Skin prick tests (SPT), specific-IgE (sIgE), component-resolved
      diagnosis and the atopy patch test (APT) were compared with the reference
      standard of double-blind placebo-controlled food challenge. Seven databases were
      searched and international experts were contacted. Two reviewers independently
      identified studies, extracted data, and used QUADAS-2 to assess risk of bias.
      Where possible, meta-analysis was undertaken. RESULTS: Twenty-four (2831
      participants) studies were included. For cows' milk allergy, the pooled
      sensitivities were 53% (95% CI 33-72), 88% (95 % CI 76-94), and 87% (95% CI 75
      94), and specificities were 88% (95% CI 76-95), 68% (95% CI 56-77), and 48% (95%
      CI 36-59) for APT, SPT, and sIgE, respectively. For egg, pooled sensitivities
      were 92% (95% CI 80-97) and 93% (95% CI 82-98), and specificities were 58% (95%
      CI 49-67) and 49% (40-58%) for skin prick tests and specific-IgE. For wheat,
      pooled sensitivities were 73% (95% CI 56-85) and 83% (95% CI 69-92), and
      specificities were 73% (95% CI 48-89) and 43% (95% CI 20-69%) for SPT and sIgE.
      For soy, pooled sensitivities were 55% (95% CI 33-75) and 83% (95% CI 64-93), and
      specificities were 68% (95% CI 52-80) and 38% (95% CI 24-54) for SPT and sIgE.
      For peanut, pooled sensitivities were 95% (95% CI 88-98) and 96% (95% CI 92-98),
      and specificities were 61% (95% CI 47-74), and 59% (95% CI 45-72) for SPT and
      sIgE. CONCLUSIONS: The evidence base is limited and weak and is therefore
      difficult to interpret. Overall, SPT and sIgE appear sensitive although not
      specific for diagnosing IgE-mediated food allergy.

PMID- 24329962
TI  - Association of caspase-14 and filaggrin expression with keratinization of the
      oral mucosa and reconstruction culture rat models.
AB  - BACKGROUND AND OBJECTIVE: Keratinization of the oral mucosa, such as the gingiva,
      has been shown to be important for periodontal health. Caspase-14 is a protease
      that plays a role in keratinization of the epidermis. The objective of this study
      was to investigate whether the expression of caspase-14 is intimately linked with
      keratinization and to examine the effect of the main component of green tea on
      the improvement of keratinization in rat oral mucosal preparations. MATERIAL AND
      METHODS: Histological and immunohistochemical analyses and quantitative mRNA
      measurements of caspase-14 and its substrate filaggrin were performed using
      different types of rat epithelial tissue and organotypic reconstruction culture
      models derived from epithelial cells and fibroblasts taken from the rat oral
      mucosa. RESULTS: In the skin, palate, buccal mucosa and esophagus, the degree of
      keratinization appeared to be associated with expression of cytokeratin 10. The
      relative protein and mRNA expression levels of caspase-14 and filaggrin were
      consistent with the degree of keratinization in the following order: skin >
      palate > buccal mucosa > esophagus. The culture models of palatal and buccal
      mucosa retained a stratified epithelial structure. Expression of caspase-14
      appeared to be stronger in the palatal model than in the buccal model.
      Remarkably, epigallocatechin-3-gallate (EGCG) improved the localization of
      cytokeratins and increased the expression of caspase-14 and filaggrin. This
      expression was more intense in the palatal model than in the buccal model,
      indicating that both models maintain the intrinsic properties of keratinization
      of the mucosa from where the cultured cells were derived. CONCLUSIONS: These
      results suggest that keratinization is closely associated with expression of
      caspase-14 and filaggrin. Our reconstruction models are promising tools for drug
      evaluation and show that EGCG is beneficial for improving both keratinization and
      expression of the linked protease in the oral mucosa.

PMID- 24329964
TI  - Clinical practice guidelines for nurse-administered procedural sedation and
      analgesia in the cardiac catheterization laboratory: a modified Delphi study.
AB  - AIM: To develop clinical practice guidelines for nurse-administered procedural
      sedation and analgesia in the cardiac catheterization laboratory. BACKGROUND:
      Numerous studies have reported that nurse-administered procedural sedation and
      analgesia is safe. However, the broad scope of existing guidelines for the
      administration and monitoring of patients who receive sedation during medical
      procedures without an anaesthetist present means there is a lack of specific
      guidance regarding optimal nursing practices for the unique circumstances where
      nurse-administered procedural sedation and analgesia is used in the cardiac
      catheterization laboratory. METHODS: A sequential mixed methods design was used.
      Initial recommendations were produced from three studies conducted by the
      authors: an integrative review; a qualitative study; and a cross-sectional
      survey. The recommendations were revised according to responses from a modified
      Delphi study. The first Delphi round was completed by nine senior cardiac
      catheterization laboratory nurses. All but one of the draft recommendations met
      the predetermined cut-off point for inclusion with 59 responses to the second
      round. Consensus was reached on all recommendations. IMPLICATIONS FOR NURSING:
      The guidelines that were derived from the Delphi study offer 24 recommendations
      within six domains of nursing practice: Pre-procedural assessment; Pre-procedural
      patient and family education; Pre-procedural patient comfort; Intra-procedural
      patient comfort; Intra-procedural patient assessment and monitoring; and
      Postprocedural patient assessment and monitoring. CONCLUSION: These guidelines
      provide an important foundation towards the delivery of safe, consistent and
      evidence-based nursing care for the many patients who receive sedation in the
      cardiac catheterization laboratory setting.

PMID- 24329963
TI  - Haemoglobinuria is associated with chronic kidney disease and its progression in
      patients with sickle cell anaemia.
AB  - To evaluate the association between haemoglobinuria and chronic kidney disease
      (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or
      Sbeta(o) thalassaemia patients from the University of Illinois at Chicago (UIC)
      and 439 from the multi-centre Walk-Treatment of Pulmonary Hypertension and Sickle
      Cell Disease with Sildenafil Therapy (Walk-PHaSST) cohort. CKD was classified
      according to National Kidney Foundation Kidney Disease Outcomes Quality
      Initiatives guidelines. Haemoglobinuria, defined as positive haem on urine
      dipstick with absent red blood cells on microscopy, was confirmed by enzyme
      linked immunosorbent assay in a subset of patients. The prevalence of CKD was 58%
      in the UIC cohort and 54% in the Walk-PHaSST cohort, and haemoglobinuria was
      observed in 36% and 20% of the patients, respectively. Pathway analysis in both
      cohorts indicated an independent association of lactate dehydrogenase with
      haemoglobinuria and, in turn, independent associations of haemoglobinuria and age
      with CKD (P < 0.0001). After a median of 32 months of follow-up in the UIC
      cohort, haemoglobinuria was associated with progression of CKD [halving of
      estimated glomerular filtration rate or requirement for dialysis; Hazard ratio
      (HR) 13.9, 95% confidence interval (CI) 1.7-113.2, P = 0.0012] and increasing
      albuminuria (HR 3.1, 95% CI: 1.3-7.7; logrank P = 0.0035). In conclusion
      haemoglobinuria is common in SCA and is associated with CKD, consistent with a
      role for intravascular haemolysis in the pathogenesis of renal dysfunction in
      SCA. 

PMID- 24329965
TI  - Cost-effectiveness analysis of preoperative transfusion in patients with sickle
      cell disease using evidence from the TAPS trial.
AB  - The study's objective was to assess the cost-effectiveness of preoperative
      transfusion compared with no preoperative transfusion in patients with sickle
      cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle
      cell disease (HbSS/Sbeta(0) thal genotypes) undergoing elective surgery
      participated in a multicentre randomised trial, Transfusion Alternatives
      Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis
      based on evidence from that trial is presented. A decision-analytic model is used
      to incorporate long-term consequences of transfusions and acute chest syndrome.
      Costs and health benefits, expressed as quality-adjusted life years (QALYs), are
      reported from the 'within-trial' analysis and for the decision-analytic model.
      The probability of cost-effectiveness for each form of management is calculated
      taking into account the small sample size and other sources of uncertainty. In
      the range of scenarios considered in the analysis, preoperative transfusion was
      more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206
      per patient, and also less costly in all but one scenario, with the mean cost
      difference ranging from -L813 to L26. All scenarios suggested preoperative
      transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness
      threshold of L20 000 per QALY. 

PMID- 24329966
TI  - Home interventions are effective at decreasing indoor nitrogen dioxide
      concentrations.
AB  - Nitrogen dioxide (NO2 ), a by-product of combustion produced by indoor gas
      appliances such as cooking stoves, is associated with respiratory symptoms in
      those with obstructive airways disease. We conducted a three-armed randomized
      trial to evaluate the efficacy of interventions aimed at reducing indoor NO2
      concentrations in homes with unvented gas stoves: (i) replacement of existing gas
      stove with electric stove; (ii) installation of ventilation hood over existing
      gas stove; and (iii) placement of air purifiers with high-efficiency particulate
      air (HEPA) and carbon filters. Home inspection and NO2 monitoring were conducted
      at 1 week pre-intervention and at 1 week and 3 months post-intervention. Stove
      replacement resulted in a 51% and 42% decrease in median NO2 concentration at 3
      months of follow-up in the kitchen and bedroom, respectively (P = 0.01, P =
      0.01); air purifier placement resulted in an immediate decrease in median NO2
      concentration in the kitchen (27%, P < 0.01) and bedroom (22%, P = 0.02), but at
      3 months, a significant reduction was seen only in the kitchen (20%, P = 0.05).
      NO2 concentrations in the kitchen and bedroom did not significantly change
      following ventilation hood installation. Replacing unvented gas stoves with
      electric stoves or placement of air purifiers with HEPA and carbon filters can
      decrease indoor NO2 concentrations in urban homes. PRACTICAL IMPLICATIONS:
      Several combustion sources unique to the residential indoor environment,
      including gas stoves, produce nitrogen dioxide (NO2), and higher NO2
      concentrations, are associated with worse respiratory morbidity in people with
      obstructive lung disease. A handful of studies have modified the indoor
      environment by replacing unvented gas heaters; this study, to our knowledge, is
      the first randomized study to target unvented gas stoves. The results of this
      study show that simple home interventions, including replacement of an unvented
      gas stove with an electric stove or placement of HEPA air purifiers with carbon
      filters, can significantly decrease indoor NO2 concentrations.

PMID- 24329967
TI  - Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian
      pacemaker of the brain. It co-ordinates the daily rhythms of sleep and
      wakefulness, as well as physiology and behaviour, that set the tempo to our
      lives. Disturbance of this daily pattern, most acutely with jet-lag but more
      insidiously with rotational shift-work, can have severely deleterious effects for
      mental function and long-term health. The present review considers recent
      developments in our understanding of the properties of the SCN that make it a
      robust circadian time-keeper. It first focuses on the intracellular
      transcriptional/ translational feedback loops (TTFL) that constitute the cellular
      clockwork of the SCN neurone. Daily timing by these loops pivots around the
      negative regulation of the Period (Per) and Cryptochrome (Cry) genes by their
      protein products. The period of the circadian cycle is set by the relative
      stability of Per and Cry proteins, and this can be controlled by both genetic and
      pharmacological interventions. It then considers the function of these feedback
      loops in the context of cytosolic signalling by cAMP and intracellular calcium
      ([Ca(2+) ]i ), which are both outputs from, and inputs to, the TTFL, as well as
      the critical role of vasoactive intestinal peptide (VIP) signalling in
      synchronising cellular clocks across the SCN. Synchronisation by VIP in the SCN
      is paracrine, operating over an unconventionally long time frame (i.e. 24 h) and
      wide spatial domain, mediated via the cytosolic pathways upstream of the TTFL.
      Finally, we show how intersectional pharmacogenetics can be used to control G
      protein-coupled signalling in individual SCN neurones, and how manipulation of
      Gq/[Ca(2+) ]i -signalling in VIP neurones can re-programme the circuit-level
      encoding of circadian time. Circadian pacemaking in the SCN therefore provides an
      unrivalled context in which to understand how a complex, adaptive behaviour can
      be organised by the dynamic activity of a relatively few gene products, operating
      in a clearly defined neuronal circuit, with both cell-autonomous and emergent,
      circuit-level properties.

PMID- 24329968
TI  - Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and
      decreases apoptosis via GSK3beta pathway in streptozotocin-induced alzheimer rat
      model.
AB  - Intracerebral-ventricular (ICV) injection of streptozotocin (STZ) induces an
      insulin-resistant brain state that may underlie the neural pathogenesis of
      sporadic Alzheimer disease (AD). Our previous work showed that prior ICV
      treatment of glucagon-like peptide-1 (GLP-1) could prevent STZ-induced learning
      memory impairment and tau hyperphosphorylation in the rat brain. The Chinese
      herbal medicine geniposide is known to relieve symptoms of type 2 diabetes.
      Because geniposide is thought to act as a GLP-1 receptor agonist, we investigated
      the potential therapeutic effect of geniposide on STZ-induced AD model in rats.
      Our result showed that a single injection of geniposide (50 MUM, 10 MUL) to the
      lateral ventricle prevented STZ-induced spatial learning deficit by about 40% and
      reduced tau phosphorylation by about 30% with Morris water maze test and
      quantitative immunohistochemical analysis, respectively. It has been known that
      tau protein can be phosphorylated by glycogen synthase kinase-3 (GSK3) and STZ
      can increase the activity of GSK3beta. Our result with Western blot analysis
      showed that central administration of geniposide resulted in an elevated
      expression of GSK3beta(pS-9) but suppressed GSK3beta(pY-216) indicating that
      geniposide reduced STZ-induced GSK3beta hyperactivity. In addition,
      ultrastructure analysis showed that geniposide averted STZ-induced neural
      pathology, including paired helical filament (PHF)-like structures, accumulation
      of vesicles in synaptic terminal, abnormalities of endoplasmic reticulum (ER) and
      early stage of apoptosis. In summary, our study suggests that the water soluble
      and orally active monomer of Chinese herbal medicine geniposide may serve as a
      novel therapeutic agent for the treatment of sporadic AD. 

PMID- 24329969
TI  - Taxonomic relatedness shapes bacterial assembly in activated sludge of globally
      distributed wastewater treatment plants.
AB  - Activated sludge (AS), which has been in use for 100 years, has been the most
      popular biological process in various wastewater treatment plants (WWTPs), in
      which bacteria plays central roles in pollutant removal. However, the potential
      relationship between bacteria taxa and the niches occupied by specific functional
      bacteria in AS are largely unknown. Here, correlation-based network analysis was
      applied to a 16S rRNA gene pyrosequencing dataset containing > 760 000 sequences
      of 50 AS samples from globally distributed full-scale WWTPs. The results showed
      that (i) bacterial assembly in AS was nonrandomly arranged by taxonomic
      relatedness and (ii) intra- and inter-phylum/class co-occurrence higher than
      expected by chance was induced by multiple deterministic processes, such as
      habitat filtering and competition. Moreover, based on bacterial occupancy, a
      prevalent core set of cosmopolitan functional bacteria (e.g. multiple nitrogen
      cycling-related bacteria) was widely distributed in the AS of different WWTPs,
      showing strong ecological associations among them. Additionally, the AS network
      has statistical and structural characteristics similar to those of previously
      reported ecological networks, such as power-law connectivity distribution and
      nonrandomly connected properties. Overall, this work provides novel insights into
      the bacterial associations within AS and sheds light on the ecological rules
      guiding bacterial assembly in WWTPs. 

PMID- 24329970
TI  - Effect of silica nanoparticles on microbial biomass and silica availability in
      maize rhizosphere.
AB  - The effect of silica nanoparticles and conventional silica sources on the changes
      in microbial biomass and silica availability to pure soil and maize rhizosphere
      was studied. Nanosilica (20-40 nm) was synthesized from rice husk and
      comprehensively characterized. The efficiency of nanosilica was evaluated in
      terms of its effects on beneficial microbial population such as phosphate
      solubilizers, nitrogen fixers, silicate solubilizers, microbial biomass carbon
      and nitrogen content, and silica content in comparison with other silica sources
      such as microsilica, sodium silicate, and silicic acid. Nanosilica significantly
      (P < 0.05) enhanced microbial populations, total biomass content (C = 1508 MUg g(
      1) and N = 178 MUg g(-1) ), and silica content (14.75 mg mL(-1) ). Although
      microsilica sources enhanced factors associated with soil fertility, their use by
      maize roots and silicification in soil was found to be less. The results show
      that nanosilica plays a vital role in influencing soil nutrient content and
      microbial biota and, hence, may promote the growth of maize crop. 

PMID- 24329971
TI  - The PpCMT chromomethylase affects cell growth and interacts with the homolog of
      LIKE HETEROCHROMATIN PROTEIN 1 in the moss Physcomitrella patens.
AB  - Chromomethylases (CMTs) are plant-specific cytosine DNA methyltransferases that
      are involved in maintenance of CpNpG methylation. In seed plants, histone
      methylation and interaction of CMT with LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) is
      essential for recruitment of CMT to target sites. LHP1 has been characterized as
      a putative component of the POLYCOMB REPRESSIVE COMPLEX1 (PRC1) in plants, and
      functions downstream of PRC2 to maintain genes in repressed state for
      orchestrated development. In the present study, we show that targeted disruption
      of PpCMT results in an approximately 50% reduction in global cytosine methylation
      levels. This affects growth of apical cells, predominantly growth of side branch
      initials emerging from chloronema cells. In some places, these cells develop
      thick walls with plasmolyzed cellular contents. Transcript accumulation patterns
      of genes involved in apical cell extension and metabolism of hemicelluloses, such
      as xyloglucans, in the primary cell walls decreased many fold in ppcmt mutant
      lines, as determined by real-time PCR. Using yeast two-hybrid method and
      bimolecular fluorescence complementation assay, we show that PpCMT and PpLHP1
      interact through their chromo domains, while PpLHP1 homodimerizes through its
      chromo shadow domain. The results presented in this study provide insight into
      the role of the single chromomethylase, PpCMT, in proliferation of protonema
      filaments, and shed light on the evolutionary conservation of proteins
      interacting with these methylases in the early land plant, Physcomitrella patens.

PMID- 24329973
TI  - Attenuating initial beliefs: increasing the acceptance of anthropogenic climate
      change information by reflecting on values.
AB  - Anthropogenic climate change information tends to be interpreted against the
      backdrop of initial environmental beliefs, which can lead to some people being
      resistant toward the information. In this article (N = 88), we examined whether
      self-affirmation via reflection on personally important values could attenuate
      the impact of initial beliefs on the acceptance of anthropogenic climate change
      evidence. Our findings showed that initial beliefs about the human impact on
      ecological stability influenced the acceptance of information only among
      nonaffirmed participants. Self-affirmed participants who were initially resistant
      toward the information showed stronger beliefs in the existence of climate change
      risks and greater acknowledgment that individual efficacy has a role to play in
      reducing climate change risks than did their nonaffirmed counterparts. 

PMID- 24329972
TI  - Cost-effectiveness of extended cessation treatment for older smokers.
AB  - AIMS: We examined the cost-effectiveness of extended smoking cessation treatment
      in older smokers. DESIGN: Participants who completed a 12-week smoking cessation
      program were factorial randomized to extended cognitive behavioral treatment and
      extended nicotine replacement therapy. SETTING: A free-standing smoking cessation
      clinic. PARTICIPANTS: A total of 402 smokers aged 50 years and older were
      recruited from the community. MEASUREMENTS: The trial measured biochemically
      verified abstinence from cigarettes after 2 years and the quantity of smoking
      cessation services utilized. Trial findings were combined with literature on
      changes in smoking status and the age- and gender-adjusted effect of smoking on
      health-care cost, mortality and quality of life over the long term in a Markov
      model of cost-effectiveness over a lifetime horizon. FINDINGS: The addition of
      extended cognitive behavioral therapy added $83 in smoking cessation services
      cost [P = 0.012, confidence interval (CI) = $22-212]. At the end of follow-up,
      cigarette abstinence rates were 50.0% with extended cognitive behavioral therapy
      and 37.2% without this therapy (P < 0.05, odds ratio 1.69, CI 1.18-2.54). The
      model-based incremental cost-effectiveness ratio was $6324 per quality-adjusted
      life year (QALY). Probabilistic sensitivity analysis found that the additional
      $947 in lifetime cost of the intervention had a 95% confidence interval of -$331
      to 2081; the 0.15 additional QALYs had a confidence interval of 0.035-0.280, and
      that the intervention was cost-effective against a $50 000/QALY acceptance
      criterion in 99.6% of the replicates. Extended nicotine replacement therapy was
      not cost-effective. CONCLUSIONS: Adding extended cognitive behavior therapy to
      standard cessation treatment was cost-effective. Further intensification of
      treatment may be warranted.

PMID- 24329974
TI  - hVISA and MRSA endocarditis: an 8-year experience in a tertiary care centre.
AB  - It is not clear if patients with heterogeneous intermediate resistance to
      vancomycin (hVISA) infectious endocarditis (IE) differ from methicillin-resistant
      S. aureus (MRSA) IE patients. All cases of hVISA and MRSA IE diagnosed at the
      Sheba Medical Centre from 2003 to 2010 were included. Isolates were screened
      prospectively for hVISA. Medical records were reviewed. The t-test, chi-square
      test, Fisher exact test and Kaplan Meier analysis were used. Fourteen hVISA IE
      and 32 MRSA IE were identified. The mean age was 76 years, mean Charlson score
      was 4.5 and 24% of patients had prosthetic valves. Pacemakers and implantable
      cardioverter-defibrillators (P/ICDs) were more common in the hVISA group (50% vs.
      22%, p 0.05). P/ICDs IE occurred in 29% of hVISA patients vs. 6.3% of MRSA
      patients (p 0.06). hVISA patients had more positive blood cultures (eight vs.
      five, p 0.007) and a trend toward longer bacteraemia (15 vs. 7.5 days, p 0.08).
      Vancomycin minimal inhibitory concentrations (MICs) were similar in the two
      groups (1.5 MUg/mL vs. 1.1 MUg/mL, p 0.11). The MIC to daptomycin was higher in
      hVISA (0.75 MUg/mL vs. 0.32 MUg/mL, p 0.049). MRSA patients received vancomycin.
      hVISA patients were switched to other antibiotics. Cardiac surgery and/or P/ICD
      extraction was performed more commonly in hVISA patients (50% vs. 16%, p 0.027).
      Mortality was high in both groups (57-66%). The median time to death was 39 days
      in the hVISA group and 19 days in the MRSA group (p 0.3). hVISA IE is associated
      with P/ICDs. Both hVISA and MRSA are associated with high mortality. Low rates of
      surgical intervention and P/ICD extraction reflect the high co-morbidity of
      patients. Caution should be employed in the empirical use of daptomycin in hVISA
      patients.

PMID- 24329975
TI  - Oral administration of Lactobacillus brevis KB290 to mice alleviates clinical
      symptoms following influenza virus infection.
AB  - Lactobacillus brevis KB290 (KB290), isolated from a traditional Japanese pickle
      'Suguki', has been reported to have immunomodulatory effects. We investigated
      whether oral administration of KB290 has protective effects against influenza
      virus (IFV) infection in mice. After 14 days of administration of lyophilized
      KB290 suspended in phosphate-buffered saline by oral gavage, BALB/c mice were
      intranasally infected with 2 * MLD50 (50% mouse lethal dose) of IFV A/PR/8/34
      (H1N1). Prophylactically administered KB290 significantly alleviated the loss of
      body weight and the deterioration in observational physical conditions induced by
      the infection. In addition, 7 days after infection, the levels of IFV-specific
      immunoglobulin (Ig)A in bronchoalveolar lavage fluid were significantly increased
      in mice fed KB290 compared with controls. Moreover, there was a significant
      elevation of serum interferon (IFN)-alpha in KB290 group mice, even at three and
      7 days after infection, despite the administration of KB290 being stopped before
      IFV infection. Our results demonstrated that oral administration of KB290 before
      infection could alleviate IFV-induced clinical symptoms. Alleviation of clinical
      symptoms by KB290 consumption may have been induced by long-lasting enhancement
      of IFN-alpha production and the augmentation of IFV-specific IgA production.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that oral
      administration of Lactobacillus brevis KB290 (KB290), a probiotic strain derived
      from a Japanese traditional pickle, could protect against influenza virus (IFV)
      infection in mice. Our results demonstrated that continual intake of KB290 for 14
      days prior to IFV infection alleviated clinical symptoms such as loss of body
      weight and deterioration in observational physical conditions induced by the
      infection. The beneficial effects of KB290 consumption may have been elicited by
      the long-lasting enhancement of interferon-alpha production and the augmentation
      of IFV-specific immunoglobulin A production.

PMID- 24329978
TI  - The effect of feed solids concentration and inlet temperature on the flavor of
      spray dried whey protein concentrate.
AB  - Previous research has demonstrated that unit operations in whey protein
      manufacture promote off-flavor production in whey protein. The objective of this
      study was to determine the effects of feed solids concentration in liquid
      retentate and spray drier inlet temperature on the flavor of dried whey protein
      concentrate (WPC). Cheddar cheese whey was manufactured, fat-separated,
      pasteurized, bleached (250 ppm hydrogen peroxide), and ultrafiltered (UF) to
      obtain WPC80 retentate (25% solids, wt/wt). The liquid retentate was then diluted
      with deionized water to the following solids concentrations: 25%, 18%, and 10%.
      Each of the treatments was then spray dried at the following temperatures: 180 
      degrees C, 200  degrees C, and 220  degrees C. The experiment was replicated 3
      times. Flavor of the WPC80 was evaluated by sensory and instrumental analyses.
      Particle size and surface free fat were also analyzed. Both main effects (solids
      concentration and inlet temperature) and interactions were investigated. WPC80
      spray dried at 10% feed solids concentration had increased surface free fat,
      increased intensities of overall aroma, cabbage and cardboard flavors and
      increased concentrations of pentanal, hexanal, heptanal, decanal, (E)2-decenal,
      DMTS, DMDS, and 2,4-decadienal (P < 0.05) compared to WPC80 spray dried at 25%
      feed solids. Product spray dried at lower inlet temperature also had increased
      surface free fat and increased intensity of cardboard flavor and increased
      concentrations of pentanal, (Z)4-heptenal, nonanal, decanal, 2,4-nonadienal, 2,4
      decadienal, and 2- and 3-methyl butanal (P < 0.05) compared to product spray
      dried at higher inlet temperature. Particle size was higher for powders from
      increased feed solids concentration and increased inlet temperature (P < 0.05).
      An increase in feed solids concentration in the liquid retentate and inlet
      temperature within the parameters evaluated decreased off-flavor intensity in the
      resulting WPC80. 

PMID- 24329977
TI  - Trs20 is required for TRAPP III complex assembly at the PAS and its function in
      autophagy.
AB  - The modular TRAPP complex acts as a guanine-nucleotide exchange factor (GEF) for
      Ypt/Rab GTPases. Whereas TRAPP I and TRAPP II regulate the exocytic pathway,
      TRAPP III functions in autophagy. The TRAPP subunit Trs20 is not required for
      assembly of core TRAPP or its Ypt1 GEF activity. Interestingly, mutations in the
      human functional ortholog of Trs20, Sedlin, cause spondyloepiphyseal dysplasia
      tarda (SEDT), a cartilage-specific disorder. We have shown that Trs20 is required
      for TRAPP II assembly and identified a SEDT-linked mutation, Trs20-D46Y, which
      causes a defect in this process. Here we show that Trs20 is also required for
      assembly of TRAPP III at the pre-autophagosomal structure (PAS). First,
      recombinant Trs85, a TRAPP III-specific subunit, associates with TRAPP only in
      the presence of Trs20, but not Trs20-D46Y mutant protein. Second, a TRAPP complex
      with Ypt1 GEF activity co-precipitates with Trs85 from wild type, but not trs20ts
      mutant, cell lysates. Third, live-cell colocalization analysis indicates that
      Trs85 recruits core TRAPP to the PAS via the linker protein Trs20. Finally,
      trs20ts mutant cells are defective in selective and non-selective autophagy.
      Together, our results show that Trs20 plays a role as an adaptor in the assembly
      of TRAPP II and TRAPP III complexes, and the SEDT-linked mutation causes a defect
      in both processes. 

PMID- 24329979
TI  - SOX-10 expression in cutaneous myoepitheliomas and mixed tumors.
AB  - BACKGROUND: SOX-10 expression can be demonstrated by immunohistochemistry in
      salivary gland myoepitheliomas, but its expression in cutaneous myoepitheliomas
      and in cutaneous mixed tumors with prominent myoepithelial cells has not been
      studied. METHODS: We assessed the staining pattern of SOX-10 in five cutaneous
      myoepitheliomas and six cutaneous mixed tumors with a prominent myoepithelial
      component among both the myoepithelial cells and cells lining lumens. In
      addition, we examined the staining of S100, microphthalmia-associated
      transcription factor (MiTF), keratin cocktail, HMK903, smooth muscle actin (SMA)
      and epithelial membrane antigen (EMA). RESULTS: SOX-10 positivity was seen in
      three of five (60%) cutaneous myoepitheliomas and in the myoepithelial cells of
      all cutaneous mixed tumors. SOX-10 expression on the cells lining the glandular
      structures in mixed tumors was variable. All myoepitheliomas and mixed tumors
      stained positively with S100 and negatively with MiTF. Pan-keratin, HMK903, SMA
      and EMA showed variable expression. CONCLUSIONS: SOX-10 is a relatively reliable
      marker for staining cutaneous myoepitheliomas. Cutaneous myoepitheliomas are
      notoriously difficult to diagnose, and the addition of SOX-10 to the repertoire
      of stains that can label this tumor is of practical utility. These results
      further support that cutaneous myoepitheliomas and cutaneous mixed tumors exist
      on a morphologic and immunophenotypic spectrum.

PMID- 24329980
TI  - An exploratory study of the patients' sleep patterns and inflammatory response
      following cardiopulmonary bypass (CPB).
AB  - AIMS AND OBJECTIVES: To describe sleep patterns and inflammatory response
      postCPB, determine sleep pattern changes and inflammatory response over time and
      explore relationships between sleep and biomarkers of stress and inflammation.
      BACKGROUND: Despite the numerous citations of the role of sleep in restoration
      and health maintenance, a paucity of research exists about this phenomenon in
      patients undergoing CPB. Specifically, there is no research that has explored
      correlations between sleep patterns and systemic inflammatory response in adult
      cardiac surgery patients. DESIGN: Exploratory, repeated-measures, correlational
      study. METHOD: Subjects were recruited from a Midwestern urban hospital. Of the
      25 eligible subjects, 16 males and four females completed the study. Wrist
      actigraphy was used to measure sleep variables. Salivary cortisol and C-reactive
      protein (C-RP) levels were measured daily. Data were collected during
      postoperative nights/days 1 through 4 (T1-T4). RESULTS: Subjects' sleep onset
      latency (SOL) median scores (0 minute) were within normal range across time
      periods, whereas median scores for wake after sleep onset (WASO > 270 minutes),
      sleep fragmentation index (SFI >51%), total sleep time (<153 minutes) and sleep
      efficiency index (SEI <36%) fell outside the normal ranges. Changes in the median
      sleep scores over time, however, were not significant at p > 0.05. Median
      cortisol levels were within normal range (0.3-0.8 MUg/dl) from T1-T4, but the C
      RP level peaked at T2 (median = 2370 pg/ml). Strong correlations were found: (1)
      between SFI-cortisol (rs = 0.82), C-RP (rs = 0.65) - WBC (rs = 0.69); (2) between
      SEI-C-RP (rs = 0.58); (3) between WASO-WBC (rs = 0.48), WASO and cross-clamp time
      (rs = 0.50); and (4) between SOL-age (rs = -0.55) at p < 0.05. CONCLUSIONS:
      Subjects were severely sleep-deprived with inflammatory response exaggerations
      warranting further investigations using larger sample sizes. RELEVANCE TO
      CLINICAL PRACTICE: This study offers a foundation for developing a conceptual
      model explaining mechanisms of sleep disturbance and inflammatory response
      postCPB. This knowledge is crucial for testing sleep-promoting interventions to
      modulate inflammatory responses essential for preventing complications, and
      restoring health.

PMID- 24329981
TI  - Endogenous sex hormones and risk of venous thromboembolism in women and men.
AB  - BACKGROUND: Use of oral contraceptives with estrogen and hormone replacement
      therapy with estrogen or testosterone are associated with increased risk of
      venous thromboembolism (VTE). However, whether endogenous estradiol and
      testosterone concentrations are also associated with risk of VTE is unknown.
      OBJECTIVE: We tested the hypothesis that elevated endogenous total estradiol and
      total testosterone concentrations are associated with increased risk of VTE in
      the general population. METHODS: We studied 4658 women, not receiving exogenous
      estrogen, and 4673 men from the 1981-1983 Copenhagen City Heart Study, who had
      estradiol and testosterone concentrations measured. Of these, 636 developed VTE
      (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) during a follow-up
      of 21 years (range, 0.02-32 years). Associations between endogenous estradiol and
      testosterone concentrations and risk of VTE were estimated by Cox proportional
      hazards regression with time-dependent covariates and corrected for regression
      dilution bias. RESULTS: Multifactorially adjusted hazard ratios of VTE for
      individuals with estradiol levels >75th vs. <=25th percentile were 0.84 (95%CI,
      0.25-2.85), 1.05 (0.53-2.08) and 1.05 (0.03-35.13) for pre- and post-menopausal
      women and men, respectively. For testosterone, corresponding risk estimates were
      0.64 (0.03-12.32), 1.11 (0.66-1.86) and 1.30 (0.62-2.73). In addition, no
      associations were observed between extreme hormone percentiles (>95th vs. <=75th)
      and risk of DVT, PE or recurrent VTE. CONCLUSION: This prospective study suggests
      that high endogenous concentrations of estradiol and testosterone in women and
      men in the general population are not associated with increased risk of VTE, DVT
      or PE.

PMID- 24329982
TI  - High-dose methotrexate in the mobilization of hematopoietic stem cells for
      patients with non-Hodgkin's lymphoma: a twelve-year study in a single center.
AB  - BACKGROUND: High-dose chemotherapy followed by autologous hematopoietic stem cell
      transplantation (auto-HSCT) is a promising approach for non-Hodgkin's lymphoma
      (NHL). Higher cell doses have been associated with a faster blood count recovery
      and a reduction in transfusion requirements, infection rates, and hospitalization
      times. Mobilization failure constitutes one of the main reasons for avoiding auto
      HSCT. The role of high-dose methotrexate (MTX) as mobilization regimen is still
      unclear. STUDY DESIGN AND METHODS: The effect of high-dose MTX as a mobilization
      regimen for 67 adult patients with NHL who received auto-HSCT was studied between
      January 2001 and October 2012. The stem cells were mobilized using combination
      chemotherapy including MTX plus granulocyte-colony-stimulating factor (G-CSF) in
      33 patients (Group A), and the stem cells of the other 34 patients were mobilized
      using the same combination chemotherapy plus G-CSF without MTX (Group B).
      RESULTS: All of the patients were successfully mobilized in Group A; however, two
      patients failed in Group B. The median numbers of CD34+ cells collected were
      14.36 * 10(6) and 5.3 * 10(6) cells/kg for Groups A and B, respectively (p <
      0.05). All of the patients experienced a stable neutrophil and platelet (PLT)
      engraftment. The times to white blood cell engraftment were 8.0 days in Group A
      and 11.0 days in Group B, and the times to PLT engraftment were 12.0 days in
      Group A and 13.0 days in Group B (p < 0.05 for both variables). CONCLUSION: High
      dose MTX is a powerful regimen component for stem cell mobilization in adult
      patients with NHL.

PMID- 24329983
TI  - Does telaprevir possess a direct antidiabetic effect?
AB  - Hepatitis C virus (HCV) induces insulin resistance, which improves upon viral
      clearance. Telaprevir is a protease inhibitor effective against HCV genotype 1.
      We reported a case, whose history suggests that telaprevir may induce some
      antidiabetic effect independently of its suppression of HCV. A 56-year-old woman
      with obesity, type 2 diabetes treated with sitagliptin and metformin, and HCV
      related cirrhosis was given triple therapy with pegylated interferon-alpha,
      ribavirin and telaprevir. After 2 weeks of treatment, HCV RNA was no longer
      detectable but the patient described a pronounced drop in the capillary glucose
      levels and episodes of hypoglycaemia that compelled her to stop all antidiabetic
      treatment. One month after stopping telaprevir, she had to resume her
      antidiabetic treatment, despite a persisting virological response. Despite
      reaching a sustained virological response, her diabetes progressed. Although the
      suppression of HCV replication may have played a role in reducing glucose
      intolerance, the fact that this patient resumed her prior antidiabetic treatment
      upon completing the telaprevir treatment, while still aviremic, suggests that
      telaprevir may have an additional antidiabetic effect. Further evidence about the
      possible role and mechanisms of telaprevir as antidiabetic agent is warranted. 

PMID- 24329984
TI  - Clinical significance of isolated v lesions in paediatric renal transplant
      biopsies: muscular arteries required to refute the diagnosis of acute rejection.
AB  - Intimal vascular lesions are considered features of acute T-cell-mediated
      rejection yet can occur in the absence of tubulointerstitial inflammation, termed
      isolated 'v' lesions. The clinical significance of these lesions is unclear. The
      diagnosis requires a biopsy with the presence of arteries. The frequency of
      adequate biopsies was analysed in 89 renal transplant biopsies from 57 paediatric
      renal allograft recipients, and the incidence of isolated endarteritis was
      determined. 60 (67%) biopsies contained an artery and of these, isolated 'v'
      lesions occurred in 6 (10%). 5 (83%) biopsies with isolated 'v' lesions were
      associated with positive DSA, suggesting that these lesions may represent acute
      antibody-mediated rejection. Patients with vessel-negative biopsies had an
      increased decline in eGFR (median -20.5, IQR -24.4 to 1.2 ml/min/1.73 m(2) vs. 
      9.6, IQR -78.7 to -6.8 ml/min/1.73 m(2) ; P = 0.01). Patients with vessel
      negative biopsies were more likely to have repeat biopsy for ongoing allograft
      dysfunction, (25.0% vs. 2.4%; P < 0.01). The data suggest that isolated 'v'
      lesions are more common than previously thought. A significant proportion of
      biopsies classified as 'normal' or 'borderline change' in the absence of a large
      vessel may represent undiagnosed acute rejection. This may result in suboptimal
      therapy with possible adverse effects on renal outcome.

PMID- 24329985
TI  - Full-length cloning and phylogenetic analyses of translationally controlled
      tumour protein and ferritin genes from the Indian white prawn, Fenneropenaeus
      indicus (H. Milne Edwards).
AB  - Elucidation, through molecular analyses, of bacterial afflictions in commercially
      important aquaculture-reared shrimps is pivotal for the prevention and/or control
      of disease outbreaks. In this study, we examined the phylogenetic relatedness and
      compared the possible immune-related functional roles of both translationally
      controlled tumour protein (TCTP) and ferritin genes with previous studies. Both
      TCTP and ferritin genes were substantially upregulated in the Indian white prawn,
      Fenneropenaeus indicus (H. Milne Edwards), post-larvae following bath challenge
      with the virulent strain of bacteria, Vibrio harveyi D3. Full-length cloning of
      these genes by rapid amplification of complementary DNA ends -polymerase chain
      reaction (RACE-PCR) yielded 727-base pair (bp)-long TCTP and 1212-bp-long
      ferritin gene sequences. Their open reading frames (ORFs) were 507 and 510 bp,
      respectively. The TCTP-ORF coded for 168 amino acids with three substitutions at
      positions 37, 141, 155, and the ferritin ORF coded for 170 amino acids with no
      species-specific substitutions. Phylogenetic analysis suggested the closest
      relatedness of both TCTP and ferritin from F. indicus to Chinese white prawn,
      Fenneropenaeus chinensis (Osbeck). In addition to reporting the full-length
      sequences of these immune-relevant genes, this study highlighted their conserved
      natures, which perhaps make them important defence-related proteins in the innate
      immune system of F. indicus. 

PMID- 24329986
TI  - Electroretinography in the normal koala (Phascolarctos cinereus).
AB  - OBJECTIVE: To perform electroretinography on normal anesthetized koalas
      (Phascolarctos cinereus). ANIMALS STUDIED: Six hospitalized koalas. PROCEDURE:
      The koalas were anesthetized using alfaxalone intramuscularly and isoflurane via
      face mask, then maintained on isoflurane after endotracheal intubation. After 20
      min of dark adaptation, electroretinograms were obtained using a handheld
      electroretinography (ERG) machine using a single flash protocol at three light
      intensities: 10 mcd s/m(2) , 3000 mcd s/m(2) , and 10,000 mcd s/m(2) . RESULTS:
      At 10 mcd s/m(2) , the mean b-wave amplitude and implicit time were 49.5 MUV (SD
      +/- 33.1 and 95% CI 29.9-69.0) and 87.4 ms (SD +/- 6.5 and 95% CI 83.6-91.2). At
      3000 mcd s/m(2) , the mean a-wave amplitude and implicit time were 70.5 MUV (SD
      +/- 30.7 and 95% CI 52.3-88.7) and 20.6 ms (SD +/- 3.1 and 95% CI 18.7-22.4), and
      the mean b-wave amplitude and implicit time were 122.8 MUV (SD +/- 49.3 and 95%
      CI 93.7-151.9) and 63.1 ms (SD +/- 13.2 and 95% CI 55.3-71.0). At 10,000 mcd
      sm(2) , the mean a-wave amplitude and implicit time were 90.8 MUV (SD +/- 37.2
      and 95% CI 68.8-112.8) and 16.1 ms (SD +/- 3.1 and 95% CI 14.3-18.0), and the
      mean b-wave amplitude and implicit time were 148.3 MUV (SD +/- 54.9 and 95% CI
      115.9-180.8) and 67.4 ms (SD +/- 8.4 and 95% CI 62.5-72.3). CONCLUSION:
      Electroretinography in koalas is practical using a portable ERG system and a DTL
      thread electrode and allows for rapid assessment of retinal function.

PMID- 24329987
TI  - Clinical parameters and symptom severity in males with fecal leakage and
      incontinence.
AB  - BACKGROUND: Despite the commonality of fecal incontinence (FI) in men, few
      studies have been carried out in this patient group. The aim of the study was to
      determine the contributions of clinical and physiological factors to symptom
      severity in males with fecal leakage (FL) and FI. METHODS: The records of all
      male patients referred for evaluation of FI and FL over a 6-year period were
      analyzed. For each male case, the records of three age-matched female controls
      with FI or FL were retrieved. All patients completed symptom assessment
      questionnaires (Vaizey score) and standard anorectal manometry testing. KEY
      RESULTS: A total of 100 males and 300 age-matched female controls were included.
      Vaizey scores were similar between sexes. For all Vaizey strata, males had normal
      maximal resting pressures (MRP) as well as normal maximal squeeze pressure (MSP).
      Females had a significantly reduced MRP and MSP across all Vaizey strata. In the
      FL subgroup, males had higher MRP and MSP than females. A multivariable linear
      regression analysis in males did not identify any clinical factors predictive of
      symptoms severity. For females, increased symptom duration, abnormal Bristol
      score, and reduced MSP were associated with worsening in Vaizey score.
      CONCLUSIONS & INFERENCES: For females, FL represents one end of the severity
      spectrum of FI while in males FL has a distinct pathophysiology. Contributing
      factors to symptoms in males with FL are not identified by routine clinical
      tests; however, anorectal manometry may identify a subgroup of FL males with low
      anal sphincter pressures that may respond to targeted interventions.

PMID- 24329988
TI  - Portal vein arterialization: a salvage procedure for a totally de-arterialized
      liver. The Paul Brousse Hospital experience.
AB  - BACKGROUND: Portal vein arterialization (PVA) has been used as a salvage inflow
      technique when hepatic artery (HA) reconstruction is deemed impossible in liver
      transplantation (LT) or hepatopancreatobiliary (HPB) surgery. Outcomes and the
      management of possible complications have not been well described. METHODS: The
      present study analysed outcomes in 16 patients who underwent PVA during the
      period from February 2005 to January 2011 for HA thrombosis post-LT (n = 7) or
      after liver resection (n = 1), during curative resection for locally advanced HPB
      cancers (requiring HA interruption) (n = 7) and for HA resection without
      reconstruction (n = 1). In addition, a literature review was conducted. RESULTS:
      Nine patients were women. The median age of the patients was 58 years (range: 30
      72 years). Recovery of intrahepatic arterial signals and PVA shunt patency were
      documented using Doppler ultrasound until the last follow-up (or until shunt
      thrombosis in some cases). Of five postoperative deaths, two occurred as a result
      of haemorrhagic shock, one as a result of liver ischaemia and one as a result of
      sepsis. The fifth patient died at home of unknown cause. Three patients (19%) had
      major bleeding related to portal hypertension (PHT). Of these, two underwent re
      exploration and one underwent successful shunt embolization to control the
      bleeding. Four patients (25%) had early shunt thrombosis, two of whom underwent a
      second PVA. After a median follow-up of 13 months (range: 1-60 months), 10
      patients (63%) remained alive with normal liver function and one submitted to
      retransplantation. CONCLUSIONS: Portal vein arterialization results in acceptable
      rates of survival in relation to spontaneous outcomes in patients with completely
      de-arterialized livers. The management of complications (especially PHT) after
      the procedure is challenging. Portal vein arterialization may represent a salvage
      option or a bridge to liver retransplantation and thus may make curative
      resection in locally advanced HPB cancers with vascular involvement feasible.

PMID- 24329989
TI  - Immunophenotypic analysis of T-acute lymphoblastic leukemia. A CD5-based ETP-ALL
      perspective of non-ETP T-ALL.
AB  - T-cell antigens [CD5,CD1a,CD8] define early T-cell precursor acute lymphoblastic
      leukemia (ETP-ALL). To understand immature T-ALL of which ETP-ALL is part, we
      used these antigens to subcategorize non-ETP T-ALL for examining expression of
      myeloid/stem cell antigens (M/S) and clinical features. Using CD5 (+/-) to start
      categorization, we studied 69 routinely immunophenotyped patients with T-ALL.
      CD5(-) was a homogenous (CD8,CD1a)(-) M/S(+) ETP-ALL group (n = 9). CD5(+) cases
      were (CD8,CD1a)(-) pre-T-ALL (n = 22) or (CD8,CD1a)(+) (n = 38) thymic/cortical T
      ALL; M/S(+) 20/22 (90.91%) in former and 22/38 (57.89%) in latter (P = 0.007).
      ETP- and pre-T-ALL together (CD1a(-) ,CD5(-/+) immature T-ALL group) were nearly
      always M/S(+) (29/31; 93.55%). In multivariate analysis, only ETP-ALL predicted
      poor overall survival (P = 0.02). We conclude (i) CD5 negativity in T-ALL almost
      always means ETP-ALL. CD1a and CD8 negativity, as much as CD5, marks immaturity
      in T-ALL, and the CD5(+/-) /CD1a(-) /CD8(-) immature T-ALL group needs further
      study to understand the biology of the T-ALL-myeloid interface. (ii) ETP-ALL
      patients may be pre-T-ALL if CD2(+) ; CD2(+) , conversely, CD5(-) /CD1a(-) /CD8(
      ) pre-T ALL patients are ETP-ALL. (iii) Immunophenotypic workup of T-ALL must not
      omit CD1a, CD5, CD8 and CD2, and positivity of antigens should preferably be
      defined as recommended for ETP-ALL, so that this entity can be better evaluated
      in future studies of immature T-ALL, a group to which ETP-ALL belongs. (iv) ETP
      ALL has poor prognosis. 

PMID- 24329990
TI  - Levels and sources of volatile organic compounds in homes of children with
      asthma.
AB  - Many volatile organic compounds (VOCs) are classified as known or possible
      carcinogens, irritants, and toxicants, and VOC exposure has been associated with
      the onset and exacerbation of asthma. This study characterizes VOC levels in 126
      homes of children with asthma in Detroit, Michigan, USA. The total target VOC
      concentration ranged from 14 to 2274 MUg/m(3) (mean = 150 MUg/m(3); median = 91
      MUg/m(3)); 56 VOCs were quantified; and d-limonene, toluene, p, m-xylene, and
      ethyl acetate had the highest concentrations. Based on the potential for adverse
      health effects, priority VOCs included naphthalene, benzene, 1,4-dichlorobenzene,
      isopropylbenzene, ethylbenzene, styrene, chloroform, 1,2-dichloroethane,
      tetrachloroethene, and trichloroethylene. Concentrations varied mostly due to
      between-residence and seasonal variation. Identified emission sources included
      cigarette smoking, solvent-related emissions, renovations, household products,
      and pesticides. The effect of nearby traffic on indoor VOC levels was not
      distinguished. While concentrations in the Detroit homes were lower than levels
      found in other North American studies, many homes had elevated VOC levels,
      including compounds that are known health hazards. Thus, the identification and
      control of VOC sources are important and prudent, especially for vulnerable
      individuals. Actions and policies to reduce VOC exposures, for example, sales
      restrictions, improved product labeling, and consumer education, are recommended.
      PRACTICAL IMPLICATIONS: Total target VOC concentrations in the Detroit homes
      ranged from 14 to 2274 lg/m3, generally lower than found in earlier studies.
      However, a subset of houses had elevated concentrations, and levels of 1,4
      dichlorobenzene, naphthalene, and benzene reached levels commensurate with excess
      individual cancer risks of 10(-2), 10(-3), and 10(-4), respectively. VOC
      concentrations varied mostly due to between-residence and season effects. The
      most important sources included cigarette smoking, vehicle-related emissions,
      building renovation, solvents, household products, and pesticides.

PMID- 24329991
TI  - Naturally occurring methyl salicylate glycosides.
AB  - As an important part of non steroids anti-inflammation drug (NSAIDs), salicylate
      has developed from natural substance salicylic acid to natrium salicylicum, to
      aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic acid, is
      modified with a -COOH group integrated one methyl radical into formic ether, and
      a -OH linked with a monosaccharide, a disaccharide or a trisaccharide unit by
      glycosidic linkage. It has the similar pharmacological activities, anti
      inflammatory, analgesic, antipyretic and antithrombotic as the previous
      salicylates' without resulting in serious side effects, particularly the
      gastrointestinal toxicity. Owing to the superiority of those significant
      bioactivities, methyl salicylate glycosides have became a hot research area in
      NSAIDs for several years. This paper compiles all 9 naturally occurring methyl
      salicylate glycosides, their distribution of the resource and pharmacological
      mechanism, which could contribute to the new drug discovery. 

PMID- 24329992
TI  - Surface binding of toxins and heavy metals by probiotics.
AB  - Removal of toxic metals and toxins using microbial biomass has been introduced as
      an inexpensive, new promising method on top of conventional methods for
      decontamination of food, raw material and concentrated. In this article the
      potential application of lactic acid bacteria and yeasts as the most familiar
      probiotics to eliminate, inactivate or reduce bioavailability of contamination in
      foods and feed has been reviewed. After fast glance to beneficial health effects
      and preservative properties of lactic acid bacteria, the mechanisms which explain
      antibacterial and antifungal efficiency as well as their antifungal metabolites
      are mentioned. Then the article has been focused on potential application of
      single strain or combination of lactic acid bacteria for removal of heavy metals
      (copper, lead, cadmium, chromium, arsenic), cyanotoxins (microcystin-LR, -RR, 
      LF) and mycotoxins (aflatoxin B1, B2, B2a, M1, M2, G1, G2, patulin, ochratoxin A,
      deoxynivalenol, fumonisin B1 and B2, 3-acetyldeoxynivalenol, deoxynivalenol,
      fusarenon, nivalenol, diacetoxyscirpenol, HT-2 and T-2 toxin, zearalenone and its
      derivative, etc) from aqueous solutions in vitro. Wherever possible the mechanism
      of decontamination and the factors influencing yield of removal are discussed.
      Some factors which can facilitate metal removal capacity of lactic acid bacteria
      including the strains, surface charge, pH, temperature, presence of other cations
      are introduced. The cell wall structure of lactic acid bacteria and yeasts are
      also introduced for further explanation of mechanism of action in complex binding
      of probiotic to contaminants and strength of mycotoxin- bacterium interaction. 

PMID- 24329993
TI  - Waterpipe tobacco labeling and packaging and World Health Organization Framework
      Convention on Tobacco Control (WHO FCTC): a call for action.

PMID- 24329994
TI  - Could treatment with R-HCVAD/R-MA as compared to R- CHOP truly result in improved
      outcomes for patients with high-risk diffuse large B cell lymphoma? - Response to
      Landsburg et al.

PMID- 24329995
TI  - New insights in the formation of polyhydroxyalkanoate granules (carbonosomes) and
      novel functions of poly(3-hydroxybutyrate).
AB  - The metabolism of polyhydroxybutyrate (PHB) and related polyhydroxyalkanoates
      (PHAs) has been investigated by many groups for about three decades, and good
      progress was obtained in understanding the mechanisms of biosynthesis and
      biodegradation of this class of storage molecules. However, the molecular events
      that happen at the onset of PHB synthesis and the details of the initiation of
      PHB/PHA granule formation, as well as the complex composition of the
      proteinaceous surface layer of PHB/PHA granules, have only recently come into the
      focus of research and were not reviewed yet. In this contribution, we summarize
      the progress in understanding the initiation and formation of the PHA granule
      complex at the example of Ralstonia eutropha H16 (model organism of PHB
      accumulating bacteria). Where appropriate, we include information on PHA granules
      of Pseudomonas putida as a representative species for medium-chain-length PHA
      accumulating bacteria. We suggest to replace the previous micelle mode of PHB
      granule formation by the Scaffold Model in which the PHB synthase initiation
      complex is bound to the bacterial nucleoid. In the second part, we highlight data
      on other forms of PHB: oligo-PHB with ~100 to 200 3-hydroxybutyrate (3HB) units
      and covalently bound PHB (cPHB) are unrelated in function to storage PHB but are
      presumably present in all living organisms, and therefore must be of fundamental
      importance.

PMID- 24329996
TI  - Skin disorders associated with obesity in children and adolescents: a population
      based study.
AB  - Obesity in children is a major public health concern in the United States. The
      objectives of the current study were to determine the prevalence of various
      groups of cutaneous disorders in obese children and adolescents and to compare
      the use of dermatology services in obese subjects with that those with a normal
      body mass index (BMI). This was a retrospective, population-based study at the
      Kaiser Permanente Northern California Managed Healthcare System. The main outcome
      measures were the relative risk of cutaneous disorders associated with insulin
      resistance, androgen excess, bacterial infection, fungal infection, viral
      infection, inflammation, mechanical changes, and other skin conditions
      (hidradenitis, hyperhidrosis) in three weight groups (normal, overweight, obese)
      and the number of dermatology visits. A total of 248,775 subjects were included.
      Bivariate analyses showed a higher proportion of insulin resistance disorders,
      bacterial infection, fungal infection, inflammatory disorders, mechanical
      changes, and other skin conditions in obese subjects than in subjects with a
      normal BMI (p < 0.001). Disorders of androgen excess and viral infection were
      significantly less common in obese subjects (p < 0.001). Obese subjects had
      significantly lower odds of having at least one dermatology encounter than
      subjects with a normal BMI (odds ratio = 0.92, 95% confidence interval 0.88,
      0.96, p = 0.003). Early onset obesity is associated with cutaneous disorders
      characterized by hyperproliferation, inflammation, bacterial and fungal
      infection, and mechanical changes but lower rates of disorders of androgen excess
      and viral infection. The use of dermatology services was not greater in obese
      patients. Heightened recognition and further analysis of adipose tissue as an
      endocrine organ that is capable of affecting the skin is warranted.

PMID- 24329997
TI  - Understanding visit-to-visit blood pressure variability.

PMID- 24329999
TI  - Long pacing pulses reduce phrenic nerve stimulation in left ventricular pacing.
AB  - INTRODUCTION: Phrenic nerve stimulation is a major obstacle in cardiac
      resynchronization therapy (CRT). Activation characteristics of the heart and
      phrenic nerve are different with higher chronaxie for the heart. Therefore,
      longer pulse durations could be beneficial in preventing phrenic nerve
      stimulation during CRT due to a decreased threshold for the heart compared with
      the phrenic nerve. We investigated if long pulse durations decreased left
      ventricular (LV) thresholds relatively to phrenic nerve thresholds in humans.
      METHODS AND RESULTS: Eleven patients, with indication for CRT and phrenic nerve
      stimulation at the intended pacing site, underwent determination of thresholds
      for the heart and phrenic nerve at different pulse durations (0.3-2.9
      milliseconds). The resulting strength duration curves were analyzed by
      determining chronaxie and rheobase. Comparisons for those parameters were made
      between the heart and phrenic nerve, and between the models of Weiss and Lapicque
      as well. In 9 of 11 cases, the thresholds decreased faster for the LV than for
      the phrenic nerve with increasing pulse duration. In 3 cases, the thresholds
      changed from unfavorable for LV stimulation to more than a factor 2 in favor of
      the LV. The greatest change occurred for pulse durations up to 1.5 milliseconds.
      The chronaxie of the heart was significantly higher than the chronaxie of the
      phrenic nerve (0.47 milliseconds vs. 0.22 milliseconds [P = 0.029, Lapicque] and
      0.79 milliseconds vs. 0.27 milliseconds [P = 0.033, Weiss]). CONCLUSION: Long
      pulse durations lead to a decreased threshold of the heart relatively to the
      phrenic nerve and may prevent stimulation of the phrenic nerve in a clinical
      setting.

PMID- 24329998
TI  - Transinfection: a method to investigate Wolbachia-host interactions and control
      arthropod-borne disease.
AB  - The bacterial endosymbiont Wolbachia manipulates arthropod host biology in
      numerous ways, including sex ratio distortion and differential offspring
      survival. These bacteria infect a vast array of arthropods, some of which pose
      serious agricultural and human health threats. Wolbachia-mediated phenotypes such
      as cytoplasmic incompatibility and/or pathogen interference can be used for
      vector and disease control; however, many medically important vectors and
      important agricultural species are uninfected or are infected with strains of
      Wolbachia that do not elicit phenotypes desirable for disease or pest control.
      The ability to transfer strains of Wolbachia into new hosts (transinfection) can
      create novel Wolbachia-host associations. Transinfection has two primary
      benefits. First, Wolbachia-host interactions can be examined to tease apart the
      influence of the host and bacteria on phenotypes. Second, desirable phenotypes
      induced by Wolbachia in a particular insect can be transferred to another
      recipient host. This can allow the manipulation of insect populations that
      transmit pathogens or detrimentally affect agriculture. As such, transinfection
      is a valuable tool to explore Wolbachia biology and control arthropod-borne
      disease. The present review summarizes what is currently known about Wolbachia
      transinfection methods and applications. We also provide a comprehensive list of
      published successful and unsuccessful Wolbachia transinfection attempts. 

PMID- 24330001
TI  - Complementary DNA sequences of the constant regions of T-cell antigen receptors
      alpha, beta and gamma in mandarin fish, Siniperca chuatsi Basilewsky, and their
      transcriptional changes after stimulation with Flavobacterium columnare.
AB  - In this study, the constant-region genes (Calpha, Cbeta and Cgamma) that encode
      the T-cell antigen receptor (TCR) alpha, beta and gamma chains were cloned from
      mandarin fish, Siniperca chuatsi Basilewsky, an important freshwater fish species
      in China. The complementary DNA sequences of Calpha, Cbeta and Cgamma were 843,
      716 and 906 base pairs (bp) in length and had a 465-, 289- and 360-bp 3'
      untranslated region, encoding 125, 142 and 182 amino acids, respectively. The
      amino-acid sequences of the constant regions of mandarin fish TCR alpha, beta and
      gamma chains (encoded by Calpha, Cbeta and Cgamma, respectively) were most
      similar to those of their teleost counterparts, showing 60% similarity with
      pufferfish, 48% similarity with Atlantic salmon and 57% similarity with flounder,
      respectively. The phylogenetic analysis revealed that the mandarin fish Calpha,
      Cbeta and Cgamma were clustered, respectively, with their vertebrate
      counterparts. The mandarin fish Calpha, Cbeta and Cgamma could also be separated
      into four domains: immunoglobulin; connecting peptide (CP); transmembrane (TM);
      and cytoplasmic tail. Several conserved features in mammalian TCRs were also
      found in those of mandarin fish, such as a conserved cysteine residue in the CP
      domain of Calpha, necessary for creating an interchain disulphide bond with the
      TCR beta chain, and a conserved antigen receptor TM motif in Calpha and Cbeta.
      Meanwhile, transcripts of Calpha, Cbeta and Cgamma were detectable in all
      examined organs, with a stronger signal observed in lymphoid organs. In addition,
      the temporal transcriptional changes for Calpha and Cgamma were investigated, 1,
      2, 3, 4, 5, 6 and 8 weeks after stimulation with Flavobacterium columnare, in
      head kidney, spleen, blood, thymus, gill and intestine, using real-time
      polymerase chain reaction. The results demonstrated stimulation-dependent up
      regulations in almost all tissues examined, which indicates that T cells may play
      important roles in preventing mandarin fish from bacterial invasion. In
      particular, apart from thymus, T cells were distributed mainly in gill and
      intestine, where striking up-regulation of Cgamma was also observed. These
      results will facilitate functional studies of teleost TCRs and T cells. 

PMID- 24330000
TI  - Characterizing variability in warfarin dose requirements in children using
      modelling and simulation.
AB  - AIMS: Although genetic, clinical and demographic factors have been shown to
      explain approximately half of the inter-individual variability in warfarin dose
      requirement in adults, less is known about causes of dose variability in
      children. This study aimed to identify and quantify major genetic, clinical and
      demographic sources of warfarin dose variability in children using modelling and
      simulation. METHODS: Clinical, demographic and genetic data from 163 children
      with a median age of 6.3 years (range 0.06-18.9 years), covering over 183 years
      of warfarin therapy and 6445 INR observations were used to update and optimize a
      published adult pharmacometric warfarin model for use in children. RESULTS:
      Genotype effects in children were found to be comparable with what has been
      reported for adults, with CYP2C9 explaining up to a four-fold difference in dose
      (CYP2C9 *1/*1 vs. *3/*3) and VKORC1 explaining up to a two-fold difference in
      dose (VKORC1 G/G vs. A/A), respectively. The relationship between bodyweight and
      warfarin dose was non-linear, with a three-fold difference in dose for a four
      fold difference in bodyweight. In addition, age, baseline and target INR, and
      time since initiation of therapy, but not CYP4F2 genotype, had a significant
      impact on typical warfarin dose requirements in children. CONCLUSIONS: The
      updated model provides quantitative estimates of major clinical, demographic and
      genetic factors impacting on warfarin dose variability in children. With this new
      knowledge more individualized dosing regimens can be developed and prospectively
      evaluated in the pursuit of improving both efficacy and safety of warfarin
      therapy in children.

PMID- 24330002
TI  - In vitro activity of isoimperatorin, alone and in combination, against
      Mycobacterium tuberculosis.
AB  - Previous studies have shown that isoimperatorin (IO), a furanocoumarin isolated
      from several medicinal plants, has antimycobacterial activity against
      Mycobacterium tuberculosis strain H37Rv (ATCC 27294). This study demonstrated
      that IO has antimycobacterial activity against 2 drug-sensitive and 6 drug
      resistant isolates, with minimum inhibitory concentrations (MICs) of 50-100 MUg
      ml(-1) and 100-200 MUg ml(-1), respectively. IO exhibited synergistic
      antimycobacterial effects with rifampin (RMP), isoniazid (INH) and ethambutol
      (EMB) against 6 drug-resistant strains, with fractional inhibitory concentration
      index (FICI) values of 0.133-0.472, 0.123-0.475 and 0.124-0.25, respectively. The
      IO/RMP, IO/INH and IO/EMB combination treatments had synergistic effects or no
      interaction in the 2 drug-sensitive strains and the standard strain ATCC 27294.
      The synergism of combined drugs against drug-resistant strains was better than
      drug-sensitive strains. No antagonism was observed in with the aforementioned
      combinations against all strains tested. IO exhibited relatively low cytotoxicity
      to Vero cells. Our results indicate that IO may serve as promising a template for
      future antimycobacterial drug development. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first report on the in vitro synergistic antimycobacterial effects of
      isoimperatorin (IO) in combination with three first-line drugs: rifampin (RMP),
      isoniazid (INH) and ethambutol (EMB). The results indicated that the
      antimycobacterial activity of IO was modest; however, IO was a useful and
      effective agent against Myco. tuberculosis when it was combined with first-line
      antimycobacterial drugs and is worthy of further development as a lead compound
      for the development of novel antimycobacterial therapeutic agents.

PMID- 24330003
TI  - Hospital-based nurse practitioner roles and interprofessional practice: a scoping
      review.
AB  - This scoping review provides current global understanding of the rapidly evolving
      nurse practitioner role within hospital settings, and considers the level of
      understanding of its enactment within interprofessional teamwork. Arksey and
      O'Malley's framework was used to explore recent primary research, reviews, and
      gray literature in two ways. First, hospital-based nurse practitioner literature
      was mapped to country of origin, and thematically summarized. Second, clearly
      developed and consistently defined key interprofessional concepts were identified
      in the interprofessional literature then conceptually mapped to the nurse
      practitioner studies by their operationalization. The nurse practitioner review
      located 103 abstracts. Twenty-nine, originating from four countries, met the
      inclusion criteria. The interprofessional concept review identified a total of
      137 relevant abstracts, however, only ten met the inclusion criteria.
      Understanding the nurse practitioner role within hospital teams remains limited
      due to a small number of countries producing evidence, the lack of nurse
      practitioner role title standardization hindering consistent knowledgebase
      development, and limited application and inconsistent operationalization of
      concepts within nurse practitioner research. Research focused on role enactment
      is needed to understand the uniqueness of the hospital-based nurse practitioner
      role. 

PMID- 24330004
TI  - Severe pertussis and hyperleukocytosis: is it time to change for exchange?
AB  - BACKGROUND: Pertussis is an important cause of infant death worldwide and
      continues to be a public health concern even in countries with high vaccination
      coverage. Severe (critical) pertussis with hyperleukocytosis is a severe form of
      the disease with up to 80% mortality rate. Attempts have been reported to reduce
      the white blood cell burden by exchange transfusion (ET) with conflicting
      conclusions. CASE REPORT: We report a case of critical pertussis in a neonate who
      was treated with ET, in view of a comprehensive literature review. RESULTS: The
      patient was discharged without any sequelae. CONCLUSION: ET should be considered
      in all infants suffering from critical pertussis and hyperleukocytosis, even in
      secondary care community hospitals.

PMID- 24330005
TI  - Interferon-alpha/beta for treatment of chronic hepatitis C infection in the era
      of direct-acting antiviral agents.
AB  - Type I interferons (IFN-alpha/beta), with or without ribavirin, have been the
      only agents that can eradicate the hepatitis C virus (HCV). An IFN-free regimen
      combining oral direct-acting antiviral agents (DAA) will be approved soon for
      genotype 1 patients. Here, we discuss the role of IFN-alpha/beta in the
      forthcoming "era of DAA" with consideration of limitations and concerns about IFN
      free therapies. First, the therapeutic efficacy of first-generation DAA varies
      among the different subtypes. While the rate of sustained virological response
      (SVR) is 60-90% among patients with genotype 1b, the rate often falls short of
      50% in patients with genotype 1a. IFN and ribavirin can still be indicated for
      patients with genotype 1a as a platform for combination with DAA. Second, there
      is concern about the emergence of drug-resistance resulting from inappropriate
      use of DAA. The clinical significance of pre-existing resistant variants has not
      been elucidated. Drug resistance may affect the efficacy of next-generation
      treatments. An IFN and ribavirin backbone in combination with DAA is an effective
      measure to prevent the emergence of drug resistance and/or to suppress pre
      existing resistant viruses. Third, it remains unknown whether the incidence of
      hepatocellular carcinoma (HCC) will be reduced in patients who achieve SVR with
      IFN-free regimens. In contrast, there are many reports in Japan demonstrating the
      preventive effects of IFN on the development of HCC. When patients do not achieve
      SVR with first-generation DAA, low-dose IFN maintenance therapy is a treatment
      option until the next-generation therapy with pan-genotypic potency and high
      genetic barrier become available. 

PMID- 24330006
TI  - Effectiveness and safety of novel oral anticoagulants as compared with vitamin K
      antagonists in the treatment of acute symptomatic venous thromboembolism: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: New direct oral anticoagulants (NOACs) constitute a novel treatment
      option for acute venous thromboembolism (VTE), with practical advantages.
      Individual studies have demonstrated comparable efficacy to that of vitamin K
      antagonists (VKAs) and have suggested a more favorable safety profile . We
      performed a meta-analysis to determine the efficacy and safety of NOACs as
      compared with those of VKAs in patients with acute VTE. METHODS: We searched
      MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical
      Trials Registry up to October 2013. Eligible studies included phase 3 trials
      comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs),
      absolute risk differences and numbers needed to treat (NNTs) to prevent one event
      were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall
      mortality, major bleeding, and other bleeding complications, with random-effects
      models. RESULTS: Five studies were included, investigating four NOACs
      (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute
      VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs
      were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and
      0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI
      0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149.
      The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed
      effect network analysis did not demonstrate significant differences between
      individual NOACs and rivaroxaban. CONCLUSIONS: NOACs have comparable efficacy to
      that of VKAs, and are associated with a significantly lower risk of bleeding
      complications, although the NNT to prevent one major bleed was relatively high.

PMID- 24330007
TI  - Comparison of three in vitro implant leakage testing methods.
AB  - AIMS: To assess the accuracy and sensitivity in detecting implants leakage with a
      gas-enhanced permeation test (GEPT) and to compare with a molecular- and a
      bacterial-based leakage tests. MATERIALS AND METHODS: Three implants systems were
      tested (n = 20 per group): Nobel Biocare (NB), Astra Tech (AT) and Biomet 3i
      (B3i). Implants were mounted in PVC disks and were first tested for gas pressure
      change and infiltrated saline volume over 40 min. The same implants were then
      subjected to a molecular leakage evaluation using fluorescent Dextran for 28
      days. After cleaning and sterilization, bacterial permeation (E. faecalis) was
      evaluated by selective media turbidity for another 28 days. Slopes in the
      pressure change and the perfused saline rate were used as a measure of leakage in
      the GEPT model and the times of positive events, that is, color change, after
      molecular and bacterial tests were recorded. Data were analyzed using Kolmogorov
      Smirnov/Shapiro-Wilk, Kruskal-Wallis H and Spearman's Rho tests (P < 0.05).
      RESULTS: The gas and saline (ml) leakage values accounted for 0.85 +/- 0.71 and
      0.56 +/- 0.50 ml (AT), 0.23 +/- 0.030 and 0.12 +/- 0.20 ml (NB) and 0.01 +/- 0.01
      and 0 +/- 0 ml (B3i), respectively, and were significantly different from each
      other (P < 0.001). Slope in the pressure change over time showed a significant
      positive correlation with the collected saline solution (r = 0.91; P < 0.001).
      Molecular and bacterial leakage was positive at the same implants, which also
      showed increased leakage values in the GEPT setup. The development of positive
      events in the timeline of the bacterial leakage evaluation corresponded well to
      the GEPT leakage model. CONCLUSION: The GEPT proved to be a reliable method to
      quantify leakage. The B3i showed the best sealing among the tested systems.

PMID- 24330009
TI  - Advance care planning for Maori, Pacific and Asian people: the views of New
      Zealand healthcare professionals.
AB  - Despite the benefits of advance care planning (ACP), international research has
      suggested that in pluralistic and multicultural societies such as New Zealand,
      significant differences exist in the uptake of ACP between European-based
      populations and other cultural groups [Crawley (2005)]. The purpose of this study
      was to therefore explore the views of generalist palliative care providers in
      both the community and hospital settings regarding the barriers to ACP adoption
      as well as methods to increase knowledge about ACP among Maori, Pacific and Asian
      cultural groups within New Zealand society. Eleven individual interviews, two
      joint interviews and three focus groups were conducted with health and social
      care professionals with a wide range of knowledge and experience in palliative
      care. Challenges were related to a number of issues based on culture, including
      family decision-making style, a need to 'do everything' and a reluctance to
      discuss issues surrounding dying and death. Suggestions to increase the knowledge
      of ACP included techniques to improve information access and the utilisation of
      shared norms and values to assist with discussions between Maori, Pacific and
      Asian health professionals and their patients and families/whanau. Findings
      indicate a need for more family/whanau-centred models of ACP, addressed much
      earlier in the healthcare process and within the community setting. 

PMID- 24330008
TI  - Changes in peptidergic neurotransmission during postoperative ileus in rat
      circular jejunal muscle.
AB  - BACKGROUND: Our aim was to explore unknown changes in neurotransmission with
      vasoactive intestinal peptide (VIP) and Substance P (Sub P) during postoperative
      ileus (POI). METHODS: Contractile activity of rat circular jejunal muscle strips
      was studied in five groups (n = 6/group): Naive controls, sham controls 12 h and
      3 days after laparotomy, and rats 12 h, 3 days after induction of POI. Dose
      responses to VIP (10(-10) -10(-7) M), Sub P (3 * 10(-10) -3 * 10(-7) M), and
      electrical field stimulation (EFS, to study endogenous release of
      neurotransmitters) were studied with different antagonists. Intestinal transit,
      inflammatory cells and immunoreactivity for VIP and Sub P were investigated in
      the bowel wall and cellular Finkel osteo sarcoma expression was determined in
      vagal afferent and efferent nuclei of the brainstem. KEY RESULTS: Postoperative
      ileus characterized by delayed intestinal transit and intramural inflammation was
      associated with an increased inhibitory effect of VIP on contractile activity. A
      biphasic impact was observed for Sub P with a decrease in its excitatory
      potential on contractility at 12 h, followed by a later increase 3 days
      postoperatively. Inhibitory response to EFS was increased, whereas the excitatory
      response decreased in ileus animals. VIP expression was increased in all
      postoperative animals while only animals 3 days after ileus induction showed
      increased Sub P expression in the myenteric plexus. These changes were associated
      with an activation of afferent but not efferent vagal nuclei in the brain stem.
      CONCLUSIONS & INFERENCES: Specific, time-dependent changes in peptidergic
      neurotransmission with VIP and Sub P occur during POI that are associated with
      vagal afferent activation, but are independent of the activation of efferent
      vagal pathways.

PMID- 24330010
TI  - Moderate patient-prosthesis mismatch predicts cardiac events and advanced
      functional class in young and middle-aged patients undergoing surgery due to
      severe aortic stenosis.
AB  - BACKGROUND AND AIM: The clinical impact of patient-prosthesis mismatch (PPM) on
      outcomes in young and middle-aged patients undergoing surgery for aortic valve
      replacement (AVR) remains unknown. Our objective was to examine the mid-term
      impact of PPM on overall mortality, quality of life, and cardiac events in this
      population. METHODS: All patients younger than 70 years of age undergoing
      isolated AVR from October 2005 to October 2011 were analyzed. PPM was defined as
      the indexed effective orifice area <= 0.85 cm(2) /m(2) . We studied the impact of
      PPM on mid-term overall mortality, cardiac events, and New York Heart Association
      functional class using an analysis stratified for propensity score. Cardiac
      events were defined as cardiac death, sudden death, hospital readmission due to
      angina, syncope or heart failure or reoperation on aortic prosthesis. RESULTS:
      Two hundred and ninety-three patients were included in the study, of whom 81
      (27.61%) had some degree of PPM. PPM had no impact on mid-term overall mortality
      (HR=1.45; 95% CI=0.65-3.22; p=0.36), although it had a negative impact on cardiac
      events (HR=11.52; 95% CI=5.25-25.24; p<0.001) and functional class (RR=7.55; 95%
      CI=2.59-22.03; p<0.001). CONCLUSIONS: Moderate PPM appears to be a strong and
      independent predictor of cardiac events and advanced functional class in young
      and middle-aged patients undergoing AVR for severe stenosis. However, it is
      possible that it has no impact on overall mortality.

PMID- 24330011
TI  - British HIV Association guidelines for the treatment of HIV-1-positive adults
      with antiretroviral therapy 2012 (Updated November 2013. All changed text is cast
      in yellow highlight.).

PMID- 24330020
TI  - Human diseases caused by germline and somatic abnormalities in microRNA and
      microRNA-related genes.
AB  - The human genome harbors approximately 2000 genes that encode microRNAs (miRNAs),
      small non-coding RNAs of approximately 20-22 nt that mediate post-transcriptional
      gene silencing. MiRNAs are generated from long transcripts through stepwise
      processing by the Drosha/DGCR8, Exportin-5/RanGTP and Dicer/TRBP complexes. Given
      that the expression of each individual miRNA is tightly regulated, the altered
      expression of certain miRNAs plays a pivotal role in human diseases. For
      instance, germline and somatic mutations in the genes encoding the miRNA
      processing machinery have been reported in different cancers. Furthermore,
      certain miRNA genes are encoded within regions that are deleted or duplicated in
      individuals with chromosomal abnormalities, and the fact that the knockout of
      these miRNAs in animal models results in lethality or the abnormal development of
      certain tissues indicates that these miRNA genes contribute to the disease
      phenotypes. It has also been reported that mutations in miRNA genes or in miRNA
      binding sites, which result in the impairment of tight regulation of target mRNA
      expression, cause human genetic diseases, although these cases are rare. This is
      in contrast to the aberrant expression of certain miRNAs that results from the
      impairment of transcriptional or post-transcriptional regulation, which has been
      reported frequently in various human diseases. The present review focuses on
      human diseases caused by mutations in genes encoding miRNAs and the miRNA
      processing machinery as well as in miRNA-binding sites. Furthermore, human
      diseases caused by chromosomal abnormalities that involve the deletion or
      duplication of regions harboring genes that encode miRNAs or the miRNA processing
      machinery are also introduced. 

PMID- 24330021
TI  - The emerging role of community sentinel surveillance in the understanding of the
      clinical features and epidemiology of acute Mycoplasma pneumoniae infection.
AB  - Retrospective analysis of 3984 test results for the detection of Mycoplasma
      pneumoniae performed between 2009 and 2013 in Wales was undertaken. Analysis of
      the clinical presentation of positive cases suggested that mild respiratory
      infection was common in the community and appeared to coincide with increased
      hospitalizations. Symptomatic infection was more prevalent in men, with a median
      age of 22.6 years (range <1-88 years), and 40% of hospitalized cases presented
      with pneumonia. Inclusion of M. pneumonia nucleic acid amplification tests
      (NAATs) into routine respiratory NAAT screens will increase the understanding of
      the epidemiology and clinical spectrum of acute infections in the wider
      population. 

PMID- 24330022
TI  - Isolation and characterization of lipid rafts in Emiliania huxleyi: a role for
      membrane microdomains in host-virus interactions.
AB  - Coccolithoviruses employ a suite of glycosphingolipids (GSLs) to successfully
      infect the globally important coccolithophore Emiliania huxleyi. Lipid rafts,
      chemically distinct membrane lipid microdomains that are enriched in GSLs and are
      involved in sensing extracellular stimuli and activating signalling cascades
      through protein-protein interactions, likely play a fundamental role in host
      virus interactions. Using combined lipidomics, proteomics and bioinformatics, we
      isolated and characterized the lipid and protein content of lipid rafts from
      control E. huxleyi cells and those infected with EhV86, the type strain for
      Coccolithovirus. Lipid raft-enriched fractions were isolated and purified as
      buoyant, detergent-resistant membranes (DRMs) in OptiPrep density gradients.
      Transmission electron microscopy of vesicle morphology, polymerase chain reaction
      amplification of the EhV major capsid protein gene and immunoreactivity to
      flotillin antisera served as respective physical, molecular and biochemical
      markers. Subsequent lipid characterization of DRMs via high performance liquid
      chromatography-triple quadrapole mass spectrometry revealed four distinct GSL
      classes. Parallel proteomic analysis confirmed flotillin as a major lipid raft
      protein, along with a variety of proteins affiliated with host defence,
      programmed cell death and innate immunity pathways. The detection of an EhV86
      encoded C-type lectin-containing protein confirmed that infection occurs at the
      interface between lipid rafts and cellular stress/death pathways via specific
      GSLs and raft-associated proteins. 

PMID- 24330023
TI  - Zoledronic acid in the management of bone disease as a consequence of multiple
      myeloma: a review.
AB  - BACKGROUND: Multiple myeloma (MM) is a haematological cancer associated with
      organ damage, essentially bone damage. MM continues to be considered an incurable
      disease and requires significant therapeutic resources. AIM: This manuscript
      presents a literature review of the utility of zoledronic acid (zoledronate) in
      the management of bone disease in MM. DISCUSSION: The clinical benefit of
      bisphosphonates in the prevention and treatment of bone disease in MM has been
      demonstrated in the last 10 years. A recent network meta-analysis has evaluated
      20 randomised clinical trials with nearly 7000 patients with myeloma enrolled and
      confirms the role of these agents in the prevention of pain, bone fractures and
      other skeletal-related events (SRE) in MM. However, their role on survival
      remains unclear. Zoledronate has shown significant reductions in SRE compared
      with placebo or other agents with acceptable tolerability, and recent studies
      have shown antitumoural effects for this agent, with a marginal survival benefit
      demonstrated in MM. CONCLUSIONS: Zoledronate prevents SRE in MM and presents a
      marginal survival benefit that deserves further investigation in controlled
      studies. Current clinical guidelines should be followed regarding the appropriate
      use of zoledronate in MM, to enhance its effects and to minimise its potential
      toxicity.

PMID- 24330024
TI  - Cytochrome P450 3A and P-glycoprotein drug-drug interactions with voclosporin.
AB  - AIMS: Voclosporin is a novel calcineurin inhibitor intended for prevention of
      organ graft rejection and treatment of lupus nephritis. Pharmacokinetic drug
      interactions between voclosporin and a CYP3A inhibitor, inducer and substrate and
      a P-glycoprotein inhibitor and substrate were evaluated. METHODS: Voclosporin 0.4
      mg kg(-1) was administered to 24 subjects in each of five studies, as follows:
      every 12 h (Q12H) alone and concomitantly with ketoconazole 400 mg once daily
      (QD); single dose before and single dose after rifampin 600 mg QD; Q12H where
      midazolam 7.5 mg was administered as a single dose alone before voclosporin and
      with last the dose of voclosporin; Q12H alone and concomitantly with verapamil 80
      mg every 8 h; and Q12H with digoxin 0.25 mg QD. The noncompartmental
      pharmacokinetic parameters maximal concentration (Cmax ) and area under the
      concentration-time curve (AUC) were obtained, and geometric least squares mean
      ratios and 90% confidence intervals were evaluated. RESULTS: Ketoconazole
      increased voclosporin Cmax (6.4-fold) and AUC (18-fold); rifampin reduced
      voclosporin AUC (0.9-fold); voclosporin did not change exposure of midazolam or
      alpha-hydroxy-midazolam; verapamil increased voclosporin Cmax (2.1-fold) and AUC
      (2.7-fold); and voclosporin increased digoxin Cmax (0.5-fold), AUC (0.25-fold)
      and urinary excretion (0.2-fold). CONCLUSIONS: Administration of voclosporin
      concomitantly with strong inhibitors and inducers of CYP3A resulted in increased
      and decreased exposures, respectively, and should be considered contraindicated.
      Drug-drug interactions involving voclosporin and CYP3A substrates are not
      expected. Administration of voclosporin concomitantly with inhibitors and
      substrates of P-glycoprotein resulted in increased voclosporin and substrate
      exposures, respectively. Appropriate concentration and safety monitoring is
      recommended with co-administration of voclosporin and P-glycoprotein substrates
      and inhibitors.

PMID- 24330025
TI  - SFRP5 correlates with obesity and metabolic syndrome and increases after weight
      loss in children.
AB  - OBJECTIVE: Secreted frizzled-related protein 5 (SFRP5) is a novel anti
      inflammatory adipokine, which has been shown as a mediator between obesity and
      its comorbidities. The aim of this study was to evaluate the associations of
      SFRP5 with metabolic syndrome (MetS) and the effects of lifestyle interventions
      on circulating SFRP5 levels in children. DESIGN: A cross-sectional study was
      conducted among 111 obese children and 49 lean controls, and a lifestyle
      intervention was performed in a subgroup of 31 obese children for 6 months.
      Anthropometric parameters, clinical data and circulating SFRP5 levels were
      measured at baseline and after lifestyle intervention. RESULTS: Secreted frizzled
      related protein 5 was significantly lower in obese children, especially in those
      with MetS, and negatively correlated with body mass index (BMI), waist
      circumference and homeostasis model assessment of insulin resistance. Independent
      of other well-known risk factors, SFRP5 was a significant predictor of MetS in
      children. In the longitudinal study, lifestyle intervention led to significant
      weight loss and higher SFRP5 levels. Furthermore, changes in BMI significantly
      correlated with the rising magnitude of SFRP5. CONCLUSIONS: Serum SFRP5 is
      regulated by weight status and seems to be correlated with metabolic disorders in
      children.

PMID- 24330027
TI  - Pseudotumor cerebri associated with cyclosporine use in severe atopic dermatitis.
AB  - Cyclosporine use can cause neurologic complications in 0.5% to 35% of cases,
      although the appearance of pseudotumor cerebri (PC) is exceptional. PC secondary
      to the use of cyclosporine is described mainly in individuals who have received a
      bone marrow transplant. We report the first case, to our knowledge, of PC
      secondary to the use of cyclosporine in a child with severe atopic dermatitis,
      with satisfactory resolution and without vision sequelae. 

PMID- 24330028
TI  - Preventive oral surgery before bisphosphonate administration to reduce
      osteonecrosis of the jaws.
AB  - OBJECTIVES: The intravenous injection of bisphosphonates, currently used for
      osteoporosis, myeloma, or bone metastases, can cause ONJ especially in
      consequence of trauma. To avoid trauma during bisphosphonate treatment,
      preventive oral surgery is recommended. The research aimed to evidence whether
      inflammatory and osteoclastogenic factors are not induced in oral mucosa after
      bisphosphonate treatment in patients receiving oral preventive surgery procedure
      and whether proliferation factors are not inhibited. PATIENTS AND METHODS:
      Specimens of oral mucosa were removed from healthy subjects and from patients
      undergoing preventive oral surgery before bisphosphonate treatment. The
      expression of cytokines and factors involved in osteoclast activity, cell
      proliferation, and angiogenesis were examined. RESULTS: Cytokines and RANK-L
      levels decreased significantly in mucosa from patients undergoing preventive oral
      surgery procedure before bisphosphonate treatment in comparison with their levels
      at the beginning of procedure and also in comparison with the level in patients
      treated only with bisphosphonates and not developing ONJ; conversely,
      osteoprotegerin and hydroxymethylglutaryl coenzyme A reductase significantly
      increased or not changed. CONCLUSIONS: The results suggest that preventive oral
      surgery could be able to prevent ONJ due to bisphosphonate treatment: The mucosa
      is not stimulated by bisphosphonates to cause ONJ, as bisphosphonates are
      probably not released from the bone.

PMID- 24330026
TI  - Constructing the major biosynthesis pathways for amino acids in the brown
      planthopper, Nilaparvata lugens Stal (Hemiptera: Delphacidae), based on the
      transcriptome data.
AB  - Nilaparvata lugens is a serious phloem-feeding pest of rice throughout Asia. Rice
      phloem sap can meet its nutrition requirement for sugars but not for some
      essential amino acids such as isoleucine, leucine, methionine, phenylalanine,
      tryptophan, lysine, arginine and histidine. N. lugens harbours yeast-like
      symbionts in mycetocytes formed by abdominal fat body cells. Removal of the
      symbionts results in negative physiological effects, suggesting that the
      symbionts play a pivotal role in the nitrogen metabolism. In the present paper,
      521 mRNA expressed sequence tags (ESTs) encoding 126 enzymes that were involved
      in amino acid biosynthesis were identified based on a transcriptome data, reverse
      transcription (RT)-PCR and rapid amplification of cDNA ends. Similarity analysis,
      codon usage bias, along with tissue-biased expression and phylogenetic analysis
      of a subset of ESTs, suggest that 437 ESTs out of the 521 originate from
      symbionts, and the remaining 84 mRNA fragments come from N. lugens. Accordingly,
      the biosynthesis pathways for 20 amino acids were manually constructed. It is
      postulated that both N. lugens and its symbiont can independently assimilate
      ammonia and biosynthesize seven non-essential amino acids: glutamate; glutamine;
      aspartate; asparagine; alanine; serine; and glycine. N. lugens and symbiont
      enzymes may work collaboratively to catalyse the biosynthesis of proline,
      methionine, valine, leucine, isoleucine, phenylalanine and tyrosine. We infer
      from this that symbionts function in the biosynthesis of lysine, arginine,
      tryptophan, threonine, histidine and cysteine. Our data support the previously
      proposed hypothesis, i.e. the yeast-like symbionts compensate for, at least
      partially, the amino acid needs of N. lugens.

PMID- 24330029
TI  - Inefficacy of a highly selective T-type calcium channel blocker in preventing
      atrial fibrillation related remodeling.
AB  - BACKGROUND: The T-type Ca(2+) channel (I(CaT)) blocker mibefradil prevents AF
      promoting remodeling occurring with atrial tachycardia, an action that has been
      attributed to I(CaT) inhibition. However, mibefradil has other effects, including
      ability to inhibit L-type Ca(2+) channels, Na(+) channels and cytochromes. Thus,
      the relationship between I(CaT) inhibition and remodeling protection in AF is
      still unknown. OBJECTIVE: To assess the effects of a novel highly selective Cav3
      (I(CaT)) blocker, AZ9112, on atrial remodeling induced by 1-week atrial
      tachypacing (AT-P) in dogs. METHODS: Mongrel dogs were subjected to AT-P at 400
      bpm for 7 days, with atrioventricular-node ablation and right-ventricular demand
      pacing (80 bpm) to control ventricular rate. Four groups of dogs were studied in
      investigator-blinded fashion: (1) a sham group, instrumented but without
      tachypacing or drug therapy (n = 5); (2) a placebo group, tachypaced but
      receiving placebo (n = 6); (3) a positive control tachypacing group receiving
      mibefradil (n = 6); and (4) a test drug group, subjected to tachypacing during
      oral treatment with AZ9112 (n = 8). RESULTS: One-week AT-P decreased atrial
      effective refractory period (ERP) at 6 of 8 sites and diminished rate-dependent
      atrial ERP abbreviation. Mibefradil eliminated AT-P-induced ERP-abbreviation at 4
      of these 6 sites, while AZ9112 failed to affect ERP at any. Neither drug
      significantly affected AF vulnerability or AF duration. CONCLUSIONS: I(CaT)
      blockade with the highly selective compound AZ9112 failed to prevent rate-related
      atrial remodeling. Thus, prevention of atrial electrophysiological remodeling by
      mibefradil cannot be attributed exclusively to I(CaT) blockade. These results
      indicate that I(CaT) inhibition is not likely to be a useful approach for AF
      therapy.

PMID- 24330030
TI  - Consensus statement on the diagnosis, treatment and follow-up of patients with
      primary adrenal insufficiency.
AB  - Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially
      deadly, but treatable disease. Most cases of PAI are caused by autoimmune
      destruction of the adrenal cortex. Consequently, patients with PAI are at higher
      risk of developing other autoimmune diseases. The diagnosis of PAI is often
      delayed by many months, and most patients present with symptoms of acute adrenal
      insufficiency. Because PAI is rare, even medical specialists in this therapeutic
      area rarely manage more than a few patients. Currently, the procedures for
      diagnosis, treatment and follow-up of this rare disease vary greatly within
      Europe. The common autoimmune form of PAI is characterized by the presence of 21
      hydroxylase autoantibodies; other causes should be sought if no autoantibodies
      are detected. Acute adrenal crisis is a life-threatening condition that requires
      immediate treatment. Standard replacement therapy consists of multiple daily
      doses of hydrocortisone or cortisone acetate combined with fludrocortisone.
      Annual follow-up by an endocrinologist is recommended with the focus on
      optimization of replacement therapy and detection of new autoimmune diseases.
      Patient education to enable self-adjustment of dosages of replacement therapy and
      crisis prevention is particularly important in this disease. The authors of this
      document have collaborated within an EU project (Euadrenal) to study the
      pathogenesis, describe the natural course and improve the treatment for Addison's
      disease. Based on a synthesis of this research, the available literature, and the
      views and experiences of the consortium's investigators and key experts, we now
      attempt to provide a European Expert Consensus Statement for diagnosis, treatment
      and follow-up.

PMID- 24330031
TI  - The pharmacokinetics of oclacitinib maleate, a Janus kinase inhibitor, in the
      dog.
AB  - The pharmacokinetics of oclacitinib maleate was evaluated in four separate
      studies. The absolute bioavailability study used a crossover design with 10 dogs.
      The effect of food on bioavailability was investigated in a crossover study with
      18 dogs. The breed effect on pharmacokinetics was assessed in a crossover study
      in beagles and mongrels dogs. Dose proportionality and multiple dose
      pharmacokinetics were evaluated in a parallel design study with eight dogs per
      group. In all four studies, serial blood samples for plasma were collected.
      Oclacitinib maleate was rapidly and well absorbed following oral administration,
      with a time to peak plasma concentration of <1 h and an absolute bioavailability
      of 89%. The prandial state of dogs did not significantly affect the rate or
      extent of absorption of oclacitinib maleate when dosed orally, as demonstrated by
      the lack of significant differences in pharmacokinetic parameters between the
      oral fasted and oral fed treatment groups. The pharmacokinetics of oclacitinib in
      laboratory populations of beagles and mixed breed dogs also appeared similar.
      Following oral administration, the exposure of oclacitinib maleate increased dose
      proportionally from 0.6 to 3.0 mg/kg. Additionally, across the pharmacokinetic
      studies, there were no apparent differences in oclacitinib pharmacokinetics
      attributable to sex. 

PMID- 24330032
TI  - Variation in detection limits between bacterial growth phases and precision of an
      ATP bioluminescence system.
AB  - To determine the detection limits of the SystemSure Plus, Escherichia coli and
      Staphylococcus aureus growth curve samples were taken in lag (1 h), log (6 h),
      stationary (12 h) and death phases (E. coli 144 h, Staph. aureus 72 h). At each
      time point, the log10 CFU ml(-1) was determined for the dilution where the
      SystemSure read 0 relative light units (RLU). Average detection limits were E.
      coli: lag 6.27, log 5.88, stationary 7.45 and death 6.88; Staph. aureus: lag
      4.37, log 5.15, stationary 7.88 and death 7.57. Between-run precision was
      determined with positive control; within-run precision with positive control, lag
      and log growth for each bacteria. Within-run precision mean RLU (CV): positive
      control 274 (12%), E. coli lag 1 (63%), log 2173 RLU (19%), Staph. aureus lag 2
      (58%) and log 5535 (18%). Between-run precision was 232 (16%). The precision is
      adequate with most values within the 95% confidence interval. The detection limit
      varied by 3.51 log10 for Staph. aureus and 1.47 log10 for E. coli. The lowest
      detection limits were during E. coli log and Staph. aureus lag phases; the
      highest was during stationary phase. These results suggest that organism
      identification and growth phase both impact ATP RLU readings. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Surface hygiene is a critical component of food safety and
      infection control; increasingly, ATP detection by bioluminescence is used to
      evaluate surface hygiene and effective cleaning. This is the first study to show
      that the number of living and potentially infectious bacteria remaining when the
      device reads zero varies between the different bacterial life cycle phases: lag,
      log, stationary and death. ATP device users need to be aware of this information
      to use the devices appropriately.

PMID- 24330033
TI  - Motility changes induced by intraluminal FeSO4 in guinea pig jejunum.
AB  - BACKGROUND: Dietary iron supplementation is associated with gastrointestinal (GI)
      side effects including vomiting, nausea, and diarrhea. Although inorganic iron in
      high concentrations may be damaging to the intestinal mucosa, we hypothesize that
      there are physiological effects on the GI tract that occur at concentrations
      achieved by supplementation. Thus, our aim was to investigate the effect of
      intraluminal ferrous sulfate (FeSO4 ) on jejunal motility. METHODS: Segments of
      guinea pig jejunum were cannulated and the intraluminal pressure recorded with a
      transducer, while movements were recorded with a video camera. Peristaltic
      threshold was the oral pressure that evoked four consecutive propulsive
      contractions. The nutrients decanoic acid (1 mM), l-phenylalanine (50 mM), or the
      micronutrient FeSO4 (1 mM) were infused intraluminally. We also tested the effect
      of FeSO4 on electrochemically detected serotonin (5-HT, 5-hydroxytryptamine)
      released from in vitro tissues, both at rest and following mechanical
      stimulation. KEY RESULTS: The jejuna peristaltic threshold was significantly
      decreased by all three nutrients: FeSO4 : 31 +/- 2-23 +/- 3 mmH2 O; decanoic
      acid: 27 +/- 2-14 +/- 2 mmH2 O; and l-phenylalanine: 30 +/- 3-14 +/- 3mmH2 O. Of
      the three, only decanoic acid induced segmentation, while FeSO4 inhibited
      decanoic acid-induced segmentation. Resting 5-HT release was increased by FeSO4
      (128% of control), but mechanically evoked 5-HT release was reduced (70% of
      control). CONCLUSIONS & INFERENCES: These data suggest that some luminal effects
      of inorganic iron on jejunal motility could be mediated through a pathway
      involving altered release of 5-HT. A better understanding of the interaction
      between luminal iron and 5-HT containing enterochromaffin cells could improve
      iron supplementation strategies, thus reducing side effects.

PMID- 24330034
TI  - beta-Glucosidase activities of lactic acid bacteria: mechanisms, impact on
      fermented food and human health.
AB  - Through the hydrolysis of plant metabolite glucoconjugates, beta-glucosidase
      activities of lactic acid bacteria (LAB) make a significant contribution to the
      dietary and sensory attributes of fermented food. Deglucosylation can release
      attractive flavour compounds from glucosylated precursors and increases the
      bioavailability of health-promoting plant metabolites as well as that of dietary
      toxins. This review brings the current literature on LAB beta-glucosidases into
      context by providing an overview of the nutritional implications of LAB beta
      glucosidase activities. Based on biochemical and genomic information, the
      mechanisms that are currently considered to be critical for the hydrolysis of
      beta-glucosides by intestinal and food-fermenting LAB will also be reviewed. 

PMID- 24330035
TI  - Ridge expansion alone or in combination with guided bone regeneration to
      facilitate implant placement in narrow alveolar ridges: a retrospective study.
AB  - OBJECTIVE: To evaluate the long-term outcomes of ridge expansion technique in
      dealing with horizontal bony insufficiency of alveolar ridges for implant
      placement. MATERIALS AND METHODS: During the period 2004-2009, 168 patients with
      width insufficiency of alveolar ridges were treated using the ridge expansion
      technique to obtain an improved bony base for implant placement. Depending on the
      severity of width insufficiency, the surgical procedures were classified into two
      groups: ridge expansion alone (Group 1) and ridge expansion in combination with
      guided bone regeneration (Group 2). After 4-6 months of unloaded healing, the
      implants were restored. The patients were followed up until 2013 with clinical
      and radiographic examinations. RESULTS: Among the 168 patients, 11 patients
      underwent a fracture of labial/buccal bony plate during surgery, which was
      corrected by changing the procedure into bone grafting, yielding a surgical
      failure rate of 6.5%. In the remaining 157 patients successfully treated by ridge
      expansion alone or in combination with GBR, 226 implants were simultaneously
      placed as planned. No implant failed over 2.8 years (6 months to 8 years) of
      follow-up, yielding a cumulative implant survival rate of 100% in each group. Six
      implants in Group 1 and 4 implants in Group 2, although osseointegrated and in
      function, did not fulfill success criteria: Cumulative implants' success rates
      were 93.2% in Group 1 and 95.6% in Group 2. The mean marginal bone losses during
      the first year in Group 1 and Group 2 were 0.69 and 0.43 mm, respectively,
      followed by an annual loss of ~ 0.06 and 0.07 mm, respectively, in the following
      years. No clinical parameter was abnormal. Twenty-two (10.4%) implants were
      exposed to peri-implant mucositis, whereas 19 (11.0%) implant-supported
      restorations were involved in prosthetic complications. CONCLUSIONS: The
      preliminary results of this retrospective study indicate that ridge expansion
      alone or in combination with GBR can be considered an effective and safe
      procedure for treatment of width insufficiency of alveolar ridges on the purpose
      of implant application.

PMID- 24330036
TI  - A global assessment of knowledge of dental students about nicotine replacement
      therapy: findings from 43 countries.
AB  - OBJECTIVES: Knowledge of nicotine replacement therapy (NRT) is a competency that
      is expected from receiving training in the treatment for tobacco dependence. This
      study therefore assessed the knowledge of dental students in 43 countries about
      NRT. METHODS: The 2005-2011 dental Global Health Professions Student Survey data
      were analysed for 13,040 third-year dental students from 43 countries. Knowledge
      about NRT was self-reported and country-specific prevalence estimates were
      calculated. To assess for correlates of knowledge about NRT amongst dental
      students, a multivariate logistic regression model was fitted (P < 0.05), with
      pooled data from all 43 countries. The model assessed for geographical location,
      gross national income, tobacco cessation training in school, sex, current tobacco
      use and survey year. RESULTS: Amongst all dental students, the proportion that
      knew about NRT ranged from 37.0% (Mongolia) to 97.6% (Slovakia). The odds of
      knowing about NRT were lower amongst dental students in the Eastern Mediterranean
      region (aOR = 0.52; 95% CI: 0.34-0.79) compared to those in the European region.
      Dental students in upper-middle-income (aOR = 2.46; 95% CI: 1.57-3.85) and high
      income countries (aOR=4.55; 95% CI: 2.28-9.09) both had higher odds of knowing
      about NRT compared to dental students in low-income countries. Also, current use
      of any tobacco product and receipt of tobacco cessation training in school were
      both associated with higher likelihood of knowing about NRT. No significant
      gender differences in knowledge of NRT were observed. CONCLUSIONS: A large
      proportion of dental students in several countries knew about NRT. However,
      disparities in knowledge existed across regions. Enhanced efforts are needed to
      formally train dental students on tobacco cessation techniques.

PMID- 24330037
TI  - An analysis of the small RNA transcriptome of four developmental stages of the
      citrus red mite (Panonychus citri).
AB  - The citrus red mite (Panonychus citri) can feed on more than 112 plant species
      around the world. Endogenous small RNAs (sRNAs) have proved to be important
      components of gene regulation in many eukaryotes. Recently, many sRNAs have been
      shown to be involved in various biological processes, such as development in many
      animals, including insects; however, to date, no sRNAs have been reported in the
      citrus red mite. Using Illumina sequencing, several categories of sRNAs were
      identified, including 594 known microRNAs (miRNAs) grouped into 206 families and
      31 novel miRNAs in the four developmental stages of citrus red mite. In addition,
      according to bioinformatics analysis and S-Poly(T) miRNA assays, the expression
      level of many miRNAs varied among the developmental stages. Furthermore, the
      prediction of miRNAs target genes and their functional annotation indicated that
      miRNAs are involved in the regulation of multiple pathways in the citrus red
      mite. As the first report of the sRNA world in citrus red mite, the present study
      furthers our understanding of the roles played by sRNAs in the development of
      citrus red mite and the data may help to develop methods of controlling the pests
      in the field. 

PMID- 24330038
TI  - Crizotinib in refractory ALK-positive diffuse large B-cell lymphoma: a case
      report with a short-term response.

PMID- 24330039
TI  - Should DEHP be eliminated in blood bags?

PMID- 24330040
TI  - Introduction to the Special Issue. Progress in nanofluids research and patents.

PMID- 24330041
TI  - Boiling heat transfer of nanofluids--special emphasis on critical heat flux.
AB  - As innovative nanotechnology-based heat-transfer media, nanofluids have evoked
      considerable interest among researchers owing to their improved thermal
      properties as well as their extendable applications to various high-power thermal
      systems. This paper presents a comprehensive review of recent research
      developments and patents pertaining to nanofluid boiling heat transfer.
      Nanofluids definitely offer a wide range of potential improvements in boiling
      heat-transfer performance. However, experimental data available from different
      studies are currently beset by numerous contradictions, suggesting that the
      fundamental mechanisms of nanofluid boiling heat transfer are not yet well
      understood. Consequently application of these technologies has been limited in
      some aspects. Only a small number of patents related to nanofluid boiling heat
      transfer have thus far been reported in the literature. Based on the present
      review, future technological development and research requirements in this area
      are outlined in line with technical challenges. To utilize nanofluid boiling heat
      transfer technologies for practical applications, more systematic and fundamental
      studies are required to understand the physical mechanisms involved.

PMID- 24330042
TI  - Recent advances in thermal conductivity of nanofluids.
AB  - This paper presents the most recent review of research articles and patents on
      thermal conductivity on nanofluids. Larger portion of literature accounts for
      experimental investigations, which is a sign of the preference for hands-on work
      by experimentalists. Metallic, non-metallic as well as ceramic nanoparticles of
      different sizes and shapes were suspended in common heat transfer liquids and
      their thermal conductivities were measured. In contrast to previous belief, it
      has now been proven that when the nanoparticle concentration is kept low the
      degree of enhancement falls reasonably within the boundaries predicted by the
      effective medium theories. There are strong evidences to suggest that the main
      mechanisms driving the thermal conductivity behavior are nanoparticle aggregation
      and the particle Brownian motion in suspension. 

PMID- 24330043
TI  - Formulation techniques for nanofluids.
AB  - Fluids with suspended nanoparticles, commonly known as nanofluids, may be
      formulated to improve the thermal performance of industrial heat transfer systems
      and applications. Nanofluids may show enhanced thermal and electrical properties
      such as thermal conductivity, viscosity, heat transfer coefficient, dielectric
      strength, etc. However, stability problems may arise as nanoparticles usually
      have the tendency to agglomerate and sediment producing deterioration in the
      increment of these properties. In this review, we discuss patents that report
      advances in the formulation of nanofluids including: production methods,
      selection of components (nanoparticles, base fluid and surfactants), their
      chemical compositions and morphologies, and characterization techniques. Finally,
      current and future directions in the development of nanofluid formulation are
      discussed.

PMID- 24330044
TI  - Boiling heat transfer and droplet spreading of nanofluids.
AB  - Nanofluids- a new class of heat transfer fluids have recently been a very
      attractive area of research due to their fascinating thermophysical properties
      and numerous potential benefits and applications in many important fields.
      However, there are many controversies and inconsistencies in reported arguments
      and experimental results on various thermal characteristics such as effective
      thermal conductivity, convective heat transfer coefficient and boiling heat
      transfer rate of nanofluids. As of today, researchers have mostly focused on
      anomalous thermal conductivity of nanofluids. Although investigations on boiling
      and droplet spreading are very important for practical application of nanofluids
      as advanced coolants, considerably fewer efforts have been made on these thermal
      features of nanofluids. In this paper, recent research and development in boiling
      heat transfer and droplet spreading of nanofluids are reviewed together with
      summarizing most related patents on nanofluids published in literature. Review
      reveals that despite some inconsistent results nanofluids exhibit significantly
      higher boiling heat transfer performance compared to their base fluids and show
      great promises to be used as advanced heat transfer fluids in numerous
      applications. However, there is a clear lack of in-depth understanding of heat
      transport mechanisms during phase change of nanofluids. It is also found that the
      nanofluids related patents are limited and among them most of the patents are
      based on thermal conductivity enhancement and synthesising processes of specific
      type of nanofluids.

PMID- 24330045
TI  - Nanofluids used for water/wastewater treatment--a mini review.
AB  - Due to the rapid elevation of health standards and the limited water resources,
      decontamination and disinfection have become a challenging aspect of
      water/wastewater treatment. Traditional disinfection in water/wastewater
      treatment is associated with limitations, such as the production of toxic
      disinfection by-products. With the development of nanofluids, there is more and
      more interest in using nanofluids in environmental sectors, especially in
      water/wastewater treatment. Nanofluids are not strong oxidants and are not
      expected to produce harmful disinfection by-products. Nanofluids exhibit good
      disinfection properties against a wide range of bacteria, including Gram
      negative, Gram-positive and spore bacteria. Several patents disclose the
      typically used types of nanofluids and their possible disinfection/
      decontamination mechanisms. The use of different nanofluids and their
      applications in different water/wastewater treatment have also been reviewed in
      this paper.

PMID- 24330046
TI  - Rheology of nanofluids: a review.
AB  - The rheological behavior of nanofluids published in recent research papers and
      the relevant patents are reviewed in this article. Effects of various factors
      such as preparation, nanoparticle and base fluid properties, concentration,
      temperature, surface charge, and aggregation etc. on the rheological behavior of
      nanofluids are discussed. Brownian motion and nanoparticle aggregation are found
      to be the major mechanisms for rheological properties of nanofluids compared to
      the micro-sized suspensions. The importance of microstructure as means of
      understanding the mechanisms behind the rheological and heat transfer behavior of
      nanofluids is also disclosed. 

PMID- 24330047
TI  - Clinical characteristics predicting early clinical failure after 72 h of
      antibiotic treatment in women with community-onset acute pyelonephritis: a
      prospective multicentre study.
AB  - In patients with community-onset acute pyelonephritis (CO-APN), assessing the
      risk factors for poor clinical response after 72 h of antibiotic treatment (early
      clinical failure) is important. The objectives of this study were to define those
      risk factors, and to assess whether early clinical failure influences mortality
      and treatment outcomes. We prospectively collected the clinical and
      microbiological data of women with CO-APN in South Korea from March 2010 to
      February 2012. The numbers of cases in the early clinical success and early
      clinical failure groups were 840 (79.1%) and 222 (20.9%), respectively. Final
      clinical failure and mortality were higher in the early clinical failure group
      than in the early clinical success group (14.9% vs 2.3%, p <0.001; 6.8% vs 0.1%,
      p 0.001, respectively). In a multiple logistic regression model, the risk factors
      for early clinical failure among the total 1062 patients were diabetes mellitus
      (OR 1.5; 95% CI 1.1-2.1), chronic liver diseases (OR 3.3; 95% CI 1.6-6.7),
      malignancy (OR 2.2; 95% CI 1.1-4.4), Pitt score >=2 (OR 2.5; 95% CI 1.6-3.8),
      presence of azotaemia (OR 1.8; 95% CI 1.2-2.7), white blood cell count >=20
      000/mm(3) (OR 2.5; 95% CI 1.6-4.0), serum C-reactive protein level >=20 mg/dL (OR
      1.7; 95% CI 1.2-2.4), and history of antibiotic usage within the previous year
      (OR 1.5; 95% CI 1.1-2.2). Analysing the subgroup of 743 patients with CO-APN due
      to Enterobacteriaceae, fluoroquinolone resistance of the uropathogen was another
      factor associated with early clinical failure (OR 1.7; 95% CI 1.1-2.5). Simple
      variables of underlying diseases, previous antibiotic usage and initial
      laboratory test outcomes can be used to decide on the direction of treatment in
      CO-APN.

PMID- 24330048
TI  - Nationwide survey of maternal screening for mother-to-child infections in Japan.
AB  - Mother-to-child infections cause congenital infection with disease and sequelae.
      To evaluate a state of maternal blood screening for mother-to-child infections in
      Japan, we for the first time conducted a nationwide survey on obstetric
      facilities where regular maternity checkups were carried out. A questionnaire
      assessment involved an annual number of deliveries, scale of facilities and a
      state of maternal blood screening for eight pathogens. A high rate (73.7%) of
      reply to the questionnaire was achieved from 1990 facilities, covering 75.1% of
      annual number of delivery in 2011. The performance rates of blood screening were
      more than 99% for rubella virus, Treponema pallidum, human immunodeficiency virus
      (HIV), human T cell leukemia virus type 1 (HTLV-1), hepatitis B virus, and
      hepatitis C virus, while the rate was found to be only 4.5% for cytomegalovirus
      (CMV), and 48.5% for Toxoplasma gondii with large differences in regions. Most of
      the facilities performed blood tests for rubella virus, Treponema pallidum, HIV,
      hepatitis B virus and hepatitis C virus once in early pregnancy, while
      approximately 28% of the facilities performed blood tests for HTLV-1 once during
      the 2nd or 3rd trimester. Most of the facilities used HA tests for Toxoplasma
      gondii, whereas there was a wide variation in antibody measurement methods for
      CMV. Generally, the obstetric facilities in Japan have performed maternal blood
      screening properly according to the current recommendations. The results of this
      survey involve important information and are helpful for clinical practitioners. 

PMID- 24330049
TI  - Novel molecular determinants of viral susceptibility and resistance in the
      lipidome of Emiliania huxleyi.
AB  - Viruses play a key role in controlling the population dynamics of algae,
      including Emiliania huxleyi, a globally distributed haptophyte with calcite
      coccoliths that comprise ca. 50% of the sinking carbonate flux from the surface
      ocean. Emiliania huxleyi viruses (EhVs) routinely infect and terminate E. huxleyi
      blooms. EhVs are surrounded by a lipid envelope, which we found to be comprised
      largely of glycosphingolipids (GSLs) with lesser amounts of polar glycerolipids.
      Infection appears to involve membrane fusion between the virus and host, and we
      hypothesized that specific polar lipids may facilitate virus attachment. We
      identified three novel intact polar lipids in E. huxleyi strain CCMP 374 and
      EhV86, including a GSL with a monosaccharide sialic acid headgroup (sGSL); for
      all 11 E. huxleyi strains we tested, there was a direct relationship between sGSL
      content and sensitivity to infection by EhV1, EhV86 and EhV163. In mesocosms, the
      E. huxleyi population with greatest initial sGSL content had the highest rate of
      virus-induced mortality. We propose potential physiological roles for sGSL that
      would be beneficial for growth but leave cells susceptible to infection, thus
      furthering the discussion of Red Queen-based co-evolution and the cost(s) of
      sensitivity and resistance in the dynamic E. huxleyi-EhV system. 

PMID- 24330050
TI  - Foetal and placental 11beta-HSD2: a hub for developmental programming.
AB  - Foetal growth restriction (FGR), reflective of an adverse intrauterine
      environment, confers a significantly increased risk of perinatal mortality and
      morbidity. In addition, low birthweight associates with adult diseases including
      hypertension, metabolic dysfunction and behavioural disorders. A key mechanism
      underlying FGR is exposure of the foetus to glucocorticoids which, while critical
      for foetal development, in excess can reduce foetal growth and permanently alter
      organ structure and function, predisposing to disease in later life. Foetal
      glucocorticoid exposure is regulated, at least in part, by the enzyme 11beta
      hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which catalyses the
      intracellular inactivation of glucocorticoids. This enzyme is highly expressed
      within the placenta at the maternal-foetal interface, limiting the passage of
      glucocorticoids to the foetus. Expression of 11beta-HSD2 is also high in foetal
      tissues, particularly within the developing central nervous system. Down
      regulation or genetic deficiency of placental 11beta-HSD2 is associated with
      significant reductions in foetal growth and birth weight, and programmed outcomes
      in adulthood. To unravel the direct significance of 11beta-HSD2 for developmental
      programming, placental function, neurodevelopment and adult behaviour have been
      extensively investigated in a mouse knockout of 11beta-HSD2. This review
      highlights the evidence obtained from this mouse model for a critical role of
      feto-placental 11beta-HSD2 in determining the adverse programming outcomes. 

PMID- 24330051
TI  - The allocation of pancreas allografts on donor age and duration of intensive care
      unit stay: the experience of the North Italy Transplant program.
AB  - Starting in 2011, the North Italy Transplant program (NITp) has based on the
      allocation of pancreas allografts on donor age and duration of intensive care
      unit (ICU) stay, but not on donor weight or BMI. We analyzed the detailed
      allocation protocols of all NITp pancreas donors (2011-2012; n = 433). Outcome
      measures included donor characteristics and pancreas loss reasons during the
      allocation process. Twenty-three percent of the 433 pancreases offered for
      allocation were transplanted. Younger age, shorter ICU stay, traumatic brain
      death, and higher eGFR were predictors of pancreas transplant, either as
      vascularized organ or as islets. Among pancreas allografts offered to
      vascularized organ programs, 35% were indeed transplanted, and younger donor age
      was the only predictor of transplant. The most common reasons for pancreas
      withdrawal from the allocation process were donor-related factors. Among pancreas
      offered to islet programs, 48% were processed, but only 14.2% were indeed
      transplanted, with unsuccessful isolation being the most common reason for
      pancreas loss. Younger donor age and higher BMI were predictors of islet
      allograft transplant. The current allocation strategy has allowed an equal
      distribution of pancreas allografts between programs for either vascularized
      organ or islet transplant. The high rate of discarded organs remained an
      unresolved issue.

PMID- 24330052
TI  - Tree-ring stable isotopes record the impact of a foliar fungal pathogen on CO(2)
      assimilation and growth in Douglas-fir.
AB  - Swiss needle cast (SNC) is a fungal disease of Douglas-fir (Pseudotsuga
      menziesii) that has recently become prevalent in coastal areas of the Pacific
      Northwest. We used growth measurements and stable isotopes of carbon and oxygen
      in tree-rings of Douglas-fir and a non-susceptible reference species (western
      hemlock, Tsuga heterophylla) to evaluate their use as proxies for variation in
      past SNC infection, particularly in relation to potential explanatory climate
      factors. We sampled trees from an Oregon site where a fungicide trial took place
      from 1996 to 2000, which enabled the comparison of stable isotope values between
      trees with and without disease. Carbon stable isotope discrimination (Delta(13)C)
      of treated Douglas-fir tree-rings was greater than that of untreated Douglas-fir
      tree-rings during the fungicide treatment period. Both annual growth and tree
      ring Delta(13)C increased with treatment such that treated Douglas-fir had values
      similar to co-occurring western hemlock during the treatment period. There was no
      difference in the tree-ring oxygen stable isotope ratio between treated and
      untreated Douglas-fir. Tree-ring Delta(13)C of diseased Douglas-fir was
      negatively correlated with relative humidity during the two previous summers,
      consistent with increased leaf colonization by SNC under high humidity conditions
      that leads to greater disease severity in following years.

PMID- 24330053
TI  - Job strain and obesity: authors' reply to Choi et al.

PMID- 24330054
TI  - Quality has no boundaries.

PMID- 24330055
TI  - Extent of lymphadenectomy does not improve the survival of patients with renal
      cell carcinoma and nodal metastases: biases associated with the handling of
      missing data.

PMID- 24330056
TI  - Circumcision - follow-up or not?

PMID- 24330057
TI  - The age old question: who benefits from prostate cancer treatment?

PMID- 24330058
TI  - TURP remains a safe and effective alternative for benign prostatic hyperplasia
      (BPH) surgery.

PMID- 24330059
TI  - How should we best manage obesity in urology?

PMID- 24330060
TI  - Another horse is leaving the stable.

PMID- 24330061
TI  - Focal prostate therapy: will we ever know the best energy?

PMID- 24330062
TI  - Urinary diversion after radical cystectomy for bladder cancer: options, patient
      selection, and outcomes.
AB  - CONTEXT: The urinary reconstructive options available after radical cystectomy
      (RC) for bladder cancer are discussed, as are the criteria for selection of the
      most appropriate diversion, and the outcomes and complications associated with
      different diversion options. OBJECTIVE: To critically review the peer-reviewed
      literature on the function and oncological outcomes, complications, and factors
      influencing choice of procedure with urinary diversion after RC for bladder
      carcinoma. EVIDENCE ACQUISITION: A Medline search was conducted to identify
      original articles, review articles, and editorials on urinary diversion in
      patients treated with RC. Searches were limited to the English language. Keywords
      included: 'bladder cancer', 'cystectomy', 'diversion', 'neobladder', and
      'conduit'. The articles with the highest level of evidence were selected and
      reviewed, with the consensus of all of the authors of this paper. EVIDENCE
      SYNTHESIS: Both continent and incontinent diversions are available for urinary
      reconstruction after RC. In appropriately selected patients, an orthotopic
      neobladder permits the elimination of an external stoma and preservation of body
      image without compromising cancer control. However, the patient must be fully
      educated and committed to the labour-intensive rehabilitation process. He must
      also be able to perform self-catheterisation if necessary. When involvement of
      the urinary outflow tract by tumour prevents the use of an orthotopic neobladder,
      a continent cutaneous reservoir may still offer the opportunity for continence
      albeit one that requires obligate self-catheterisation. For patients who are not
      candidates for continent diversion, the ileal loop remains an acceptable and
      reliable option. CONCLUSIONS: Both continent and incontinent diversions are
      available for urinary reconstruction after RC. Orthotopic neobladders optimally
      preserve body image, while continent cutaneous diversions represent a reasonable
      alternative. Ileal conduits represent the fastest, easiest, least complication
      prone, and most commonly performed urinary diversion.

PMID- 24330063
TI  - Dairy product intake in children and adolescents in developed countries: trends,
      nutritional contribution, and a review of association with health outcomes.
AB  - Despite its contribution to nutrient intake and status, consumption of milk and
      dairy products by children and adolescents in many countries has waned in recent
      decades, with a substantial proportion of youth failing to meet intake
      recommendations. Dairy products remain an important dietary source of multiple
      micronutrients, including calcium, phosphorus, magnesium, zinc, iodine,
      potassium, vitamin A, vitamin D, vitamin B12 , and riboflavin (vitamin B2 ). In
      addition, dairy products provide children with energy, high-quality protein, and
      essential and nonessential fatty acids. A review of evidence was conducted to
      evaluate associations between milk or dairy product intake and health outcomes in
      children and adolescents. Results suggest a neutral or inverse association
      between consumption of milk and dairy products in children and adolescents and
      indicators of adiposity, incidence of dental caries, and hypertension. Available
      data indicate that dairy products are important for linear growth and bone health
      during childhood. Additional research--in particular, controlled intervention
      trials and long-term prospective cohort studies--is warranted to better
      understand how dairy intake affects health outcomes in children and adolescents.

PMID- 24330064
TI  - Oral, subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy
      cats.
AB  - Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in
      cats. The purpose of this study was to evaluate the pharmacokinetics of
      ondansetron in healthy cats. Six cats with normal complete blood count, serum
      biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous
      (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over
      manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1,
      2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron
      concentrations were measured using liquid chromatography coupled to tandem mass
      spectrometry. Noncompartmental pharmacokinetic modeling and dose interval
      modeling were performed. Repeated measures anova was used to compare parameters
      between administration routes. Bioavailability of ondansetron was 32% (oral) and
      75% (subcutaneous). Calculated elimination half-life of ondansetron was 1.84 +/-
      0.58 h (intravenous), 1.18 +/- 0.27 h (oral) and 3.17 +/- 0.53 h (subcutaneous).
      The calculated elimination half-life of subcutaneous ondansetron was
      significantly longer (P < 0.05) than oral or intravenous administration.
      Subcutaneous administration of ondansetron to healthy cats is more bioavailable
      and results in a more prolonged exposure than oral administration. This
      information will aid management of emesis in feline patients.

PMID- 24330065
TI  - Quantification of the predominant immune cell populations in decidua throughout
      human pregnancy.
AB  - PROBLEM: To date, a multiplicity of factors contributing to the establishment and
      progression of a successful pregnancy have been postulated. There is emerging
      evidence that decidual leukocytes could be decisive factors during pregnancy.
      Despite numerous investigations on immune cells in human early pregnancy decidua,
      little is known about the physiological composition and proportion of the various
      immune cell populations during the different phases of pregnancy. In this study,
      we therefore analyzed the proportion of the dominant decidual leukocytes in human
      tissue samples derived from all phases of pregnancy. METHODS: Single cell
      suspensions were prepared from decidual samples from 205 patients at 6-40 weeks
      of gestation. Cell populations were analyzed by flow cytometry, and immune cell
      populations were quantified as percentage of decidual CD45(+) cells. RESULTS:
      There was generally no difference in immune cell counts comparing decidua of
      healthy gestations and those with systemic inflammation. Overall, the proportion
      of uNK cells continuously decreased, while the amount of monocytes, immature
      dendritic cells, and T cells increased until term. Striking modifications in cell
      counts were seen during the 7th week compared with the 6th and later weeks of
      gestation. CONCLUSION: Studying the proportion of decidual immune cells during
      pregnancy, we detected a unique pattern which could be useful to design novel
      therapies for pathological conditions during pregnancy.

PMID- 24330066
TI  - The variable faces of monogenic diabetes.

PMID- 24330069
TI  - Prevalence and outcomes of laser treatment of aggressive posterior retinopathy of
      prematurity.
AB  - BACKGROUND: To describe outcomes in a cohort of extremely premature infants
      treated for aggressive posterior retinopathy of prematurity by diode laser
      panretinal photocoagulation. DESIGN: Retrospective study. PARTICIPANTS: Fifteen
      eyes in eight infants. METHODS: A review was carried out on infants between 23
      and 25.6 weeks gestational age admitted to The Royal Brisbane and Women's
      Hospital neonatal intensive care unit between 1992 and 2009. MAIN OUTCOME
      MEASURES: Success of treatment, visual and refractive outcomes. RESULTS: Five
      hundred fifty-four infants were admitted to neonatal intensive care unit, 373
      survived till screening, and 304 had retinopathy of prematurity. Sixty-six
      infants required treatment, and eight of these had aggressive posterior
      retinopathy of prematurity (2.5% of all infants with retinopathy of prematurity).
      Mean gestational age was 24.2 weeks, mean birthweight was 634 g, and treatment
      occurred at mean 34.1 weeks post-menstrual age. The mean total number of burns
      per eye was 2967. Five of 15 treated eyes required retreatment. Two patients
      subsequently died of unrelated causes. Regression occurred in 9 of 11 remaining
      eyes; one eye progressed to stage 4b and another to stage 5 retinopathy of
      prematurity. Vitrectomy was performed in two eyes. Five eyes had 6/12 vision, one
      had 3/60, and three had no perception of light. Of the remaining two eyes, one
      had good fixation and the other had poor fixation. CONCLUSIONS: Despite good
      structural outcomes, visual outcomes for conventional laser treatment of
      aggressive posterior retinopathy of prematurity are poor.

PMID- 24330068
TI  - Nuclear Raf-1 kinase regulates the CXCR5 promoter by associating with NFATc3 to
      drive retinoic acid-induced leukemic cell differentiation.
AB  - Novel functions of signaling molecules have been revealed in studies of cancer
      stem cells. Retinoic acid (RA) is an embryonic morphogen and stem cell regulator
      that controls the differentiation of a patient-derived leukemic cell line, HL-60,
      which is composed of progenitor cells with bipotent myelo-monocytic
      differentiation capability. RA treatment of HL-60 cells causes unusually long
      lasting mitogen-activated protein kinase signaling, with the cells exhibiting the
      beginning of G0 cell cycle arrest and functional differentiation by 48 h after
      treatment with RA. This event coincides with the nuclear translocation of Raf-1,
      phosphorylated at serine 621. The present study shows how the novel localization
      of Raf-1 to the nucleus results in transcriptional changes that contribute to the
      differentiation of HL-60 cells induced by RA. We find that nuclear pS621 Raf-1
      associates with NFATc3 near its cognate binding site in the promoter of CXCR5, a
      gene that must be up-regulated to drive RA-induced differentiation. NFATc3
      becomes immunoprecipitable with anti-phosphoserine serum, and CXCR5 is
      transcriptionally up-regulated upon RA-induced differentiation. Inhibiting the
      pS621 Raf-1/NFATc3 association with PD98059 inhibits these processes and cripples
      RA-induced differentiation. In this novel paradigm for Raf-1 and RA function, Raf
      1 has a role in driving the nuclear signaling of RA-induced differentiation of
      leukemic progenitor cells.

PMID- 24330070
TI  - The contributions of persons in the work environment to the self-identity of
      persons with mental health problems: a study in Israel.
AB  - This study explores the contribution of others in the workplace to the self
      identity and job integration of persons with severe mental health problems.
      Thematic content analysis of in-depth, semi-structured interviews conducted in
      2009 with 15 Israelis with severe mental health problems who work in a variety of
      frameworks (protected and supported employment and open market) revealed three
      main themes: (i) dissatisfaction with the protected work settings in which they
      were initially employed; (ii) the importance they attributed to their
      relationships with others in their workplace; and (iii) the change in self
      identity they underwent from persons defined by their mental health problems to
      persons who had worth, abilities and being beyond their illness. The findings
      underscore the important role of managers and colleagues in integrating persons
      with mental health problems at work and in strengthening the self-identity of
      those individuals. 

PMID- 24330071
TI  - Mild arterial hypertension: a form of exercise for the heart?

PMID- 24330072
TI  - Total adiponectin, but not inflammatory markers C-reactive protein, tumor
      necrosis factor-alpha, interluekin-6 and monocyte chemoattractant protein-1,
      correlates with increasing glucose intolerance in pregnant Chinese-Americans.
AB  - BACKGROUND: Elevated insulin, C-reactive protein (CRP), tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1
      levels and decreased high molecular weight adiponectin (HMW-APN) levels have been
      reported in Caucasians with gestational diabetes mellitus (GDM). No similar
      studies have been performed in Chinese women. METHODS: Serum samples were
      obtained 1 h after a 50-g glucose challenge test (1HGCT) from Chinese-American
      women at 24-28 gestational weeks and total adiponectin (T-APN), HMW-APN, CRP, TNF
      alpha, IL-6, and MCP-1 concentrations were measured. Correlation coefficients for
      glucose (1HGCT), HbA1c, insulin, and body mass index (BMI) were calculated
      against T-APN, HMW-APN, CRP, TNF-alpha, IL-6, and MCP-1. Significant P-values
      were determined using Bonferroni adjustments. RESULTS: Women with GDM had higher
      insulin and 1HGCT and lower T-APN. In addition, T-APN was lower in non-GDM
      subjects who had 1HGCT >=135 mg/dL with no abnormal or one abnormal glucose value
      on the 3-h oral glucose tolerance test. There were no significant differences in
      HMW-APN and inflammatory marker levels between non-GDM and GDM groups. There were
      negative correlations between T-APN and 1HGCT, insulin, BMI, and HbA1c, as well
      as between HMW-APN and 1HGCT, insulin, and BMI. No significant correlations were
      observed between 1HGCT, HbA1c, insulin, or BMI and CRP, TNF-alpha, IL-6, or MCP
      1. CONCLUSIONS: T-APN is reduced in Chinese women with GDM and those without GDM
      but with evidence of glucose intolerance. Unlike results reported for Caucasians,
      Chinese-American women with GDM do not exhibit elevated levels of CRP, TNF-alpha,
      IL-6, or MCP-1, possibly because Chinese women are relatively leaner compared
      with Caucasians.

PMID- 24330073
TI  - Acute hamstring strain injury in track-and-field athletes: A 3-year observational
      study at the Penn Relay Carnival.
AB  - This study aimed to observe the incidence rates of hamstring strain injuries
      (HSIs) across different competition levels and ages during the Penn Relays
      Carnival. Over a 3-year period, all injuries treated by the medical staff were
      recorded. The type of injury, anatomic location, event in which the injury
      occurred, competition level, and demographic data were documented. Absolute and
      relative HSI (per 1000 participants) were determined, and odds ratios (ORs) were
      calculated between sexes, competition levels, and events. Throughout the study
      period 48,473 athletes registered to participate in the Penn Relays Carnival,
      with 118 HSIs treated by the medical team. High school girls displayed lesser
      risk of HSI than high school boys (OR = 0.55, P = 0.021), and masters athletes
      were more likely than high school- (OR = 4.26, P < 0.001) and college-level (OR =
      3.55, P = 0.001) athletes to suffer HSI. The 4 * 400-m relay displayed a greater
      likelihood of HSI compared with the 4 * 100-m relay (OR = 1.77, P = 0.008). High
      school boys and masters-level athletes are most likely to suffer HSI, and there
      is higher risk in 400-m events compared with 100-m events.

PMID- 24330075
TI  - Signalling properties and pharmacology of a 5-HT7 -type serotonin receptor from
      Tribolium castaneum.
AB  - In the last decade, genome sequence data and gene structure information on
      invertebrate receptors has been greatly expanded by large sequencing projects and
      cloning studies. This information is of great value for the identification of
      receptors; however, functional and pharmacological data are necessary for an
      accurate receptor classification and for practical applications. In insects, an
      important group of neurotransmitter and neurohormone receptors, for which ample
      sequence information is available but pharmacological information is missing, are
      the biogenic amine G protein-coupled receptors (GPCRs). In the present study, we
      investigated the sequence information, pharmacology and signalling properties of
      a 5-HT7 -type serotonin receptor from the red flour beetle, Tribolium castaneum
      (Trica5-HT7 ). The receptor encoding cDNA shows considerable sequence similarity
      with cognate 5-HT7 receptors and phylogenetic analysis also clusters the receptor
      within this 5-HT receptor group. Real-time reverse transcription PCR demonstrated
      high expression levels in the brain, indicating the possible importance of this
      receptor in neural processes. Trica5-HT7 was dose-dependently activated by 5-HT,
      which induced elevated intracellular cyclic AMP levels but had no effect on
      calcium signalling. The synthetic agonists, alpha-methyl 5-HT, 5
      methoxytryptamine, 5-carboxamidotryptamine and 8-hydroxy-2
      (dipropylamino)tetralin hydrobromide, showed a response, although with a much
      lower potency and efficacy than 5-HT. Ketanserin and methiothepin were the most
      potent antagonists. Both showed characteristics of competitive inhibition on
      Trica5-HT7 . The signalling pathway and pharmacological profile offer important
      information that will facilitate functional and comparative studies of 5-HT
      receptors in insects and other invertebrates. The pharmacology of invertebrate 5
      HT receptors differs considerably from that of vertebrates. The present study may
      therefore contribute to establishing a more reliable classification of
      invertebrate 5-HT receptors. 

PMID- 24330074
TI  - Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced
      diabetic nephropathy.
AB  - A range of in vitro, experimental and clinical intervention studies have
      implicated an important role for hyperglycaemia-induced activation of the renin
      angiotensin system (RAS) in the development and progression of diabetic
      nephropathy (DN). Blockade of RAS by angiotensin converting enzyme (ACE)
      inhibitors is an effective strategy in treating diabetic kidney diseases.
      However, few studies demonstrate the mechanism by which hyperglycaemia up
      regulates the expression of ACE gene. Our previous studies have identified a
      novel curcumin analogue, (2E,6E)-2,6-bis(2
      (trifluoromethyl)benzylidene)cyclohexanone (C66), which could inhibit the high
      glucose (HG)-induced phosphorylation of mitogen-activated protein kinases in
      mouse macrophages. In this study, we found that the renal protection of C66 in
      diabetic mice was associated with mitogen-activated protein kinase (MAPK)
      inactivation and ACE/angiotensin II (Ang II) down-regulation. Generally, MAPKs
      have been considered as a downstream signalling of Ang II and a mediator for Ang
      II-induced pathophysiological actions. However, using C66 and specific inhibitors
      as small molecule probes, in vitro experiments demonstrate that the MAPK
      signalling pathway regulates ACE expression under HG stimulation, which
      contributes to renal Ang II activation and the development of DN. This study
      indicates that C66 is a potential candidate of DN therapeutic agents, and more
      importantly, that reduction in ACE expression by MAPKs inhibition seems to be an
      alternative strategy for the treatment of DN. 

PMID- 24330076
TI  - Assessment of nailfold capillaroscopy in systemic sclerosis by different optical
      magnification methods.
AB  - BACKGROUND: Systemic sclerosis (SSc) is characterized by target-organ fibrosis
      and microvascular dysfunction, which can be assessed using nailfold
      capillaroscopy. Dermoscopy is a useful and easily performed method for diagnosing
      skin lesions. AIM: To compare conventional capillaroscopy, using the gold
      standard method (conventional stereomicroscope nailfold capillaroscopy; SNFC),
      with polarized light noncontact dermoscopy (PNCD) and nonpolarized light contact
      dermoscopy (NPCD), and to evaluate their accuracy in diagnosing characteristic
      SSc-related alterations. METHODS: The study enrolled 45 patients with SSc.
      Capillaroscopy images and photographs were taken with three devices, SNFC, NPCD
      and PNCD, and these images were randomly analysed by a blinded observer. RESULTS:
      The scleroderma pattern was found in 83% of patients. PNCD and NPCD were highly
      sensitive in identifying the presence of focal capillary loss (96.4% and 100%,
      respectively), haemorrhage (96.2% and 92%, respectively), and scleroderma (91.9%,
      94.6%), and showed high specificity for haemorrhage and enlarged loops. The intra
      observer kappa values for detection of the scleroderma pattern by SNFC images,
      NPCD and PNCD were moderate to good: (kappa = 0.71 (95% CI 0.44-0.95), kappa =
      0.60 (95% CI 0.35-0.83) and kappa = 0.60 (95% CI 0.32-0.86), respectively.
      Evaluation of haemorrhage presence gave high kappa values for all methods: kappa
      = 0.77 (95% CI 0.57-0.95), kappa = 0.90 (95% CI 0.76-1.00) and kappa = 0.95 (95%
      CI 0.85-1.00), respectively. CONCLUSIONS: Both polarized and nonpolarized
      dermoscopy are reliable methods for valuation of nailfold capillaroscopy in
      patients with SSc. They are easy to perform, with good rates of accuracy and
      results that are comparable with traditional capillaroscopy.

PMID- 24330077
TI  - Role of sortase A in the pathogenesis of Staphylococcus aureus-induced mastitis
      in mice.
AB  - Sortase A (SrtA), a transpeptidase, anchors surface proteins with an LPXTG-motif
      sorting signal to the cell envelope. To determine the role of SrtA in the
      pathogenesis of Staphylococcus aureus, we constructed a mutant strain, ?SrtA, by
      genetic techniques and identified its functions in a S. aureus-induced mastitis
      mouse model. The histological and myeloperoxidase (MPO) level results showed that
      the ?SrtA strain attenuated the inflammatory reaction in the mammary tissue of
      mice compared with wild-type S. aureus challenge. Additionally, the ELISA results
      showed that the ?SrtA strain impaired the induction of pro-inflammatory cytokines
      such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and
      interleukin-6 (IL-6), and the Western blot results showed that the mutant strain
      blocked the activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated
      protein kinases (MAPKs) by attenuating the degradation and phosphorylation of
      signaling pathway molecules such as IkappaBalpha, p65 and p38. These results
      suggest that SrtA is a key virulence factor in the pathogenesis of S. aureus
      induced mastitis in mice. It appears that the srtA mutant affected the attachment
      of S. aureus to host cells, thus attenuating the activation of the NF-kappaB and
      MAPK signaling pathways, which regulated the expression of pro-inflammatory
      cytokines and decreased the susceptibility to mastitis.

PMID- 24330078
TI  - Psychometric validation of the Spanish version of the Dundee Ready Education
      Environment Measure applied to dental students.
AB  - AIM: To carry out a psychometric evaluation of the Spanish-language version of
      the Dundee Ready Education Environment Measure (DREEM) applied to dental
      students. METHODS: A total of 1,391 students from nine Spanish public schools of
      dentistry responded to the DREEM questionnaire. To analyse the reliability of the
      DREEM questionnaire, the internal consistency was assessed and a 'test-retest'
      carried out. Validity was evaluated through analysis of item response rate, floor
      and ceiling effects, corrected item-total and item-subscale correlations and
      factor structure. A confirmatory factor analysis was performed to analyse the
      structure of the original DREEM scale. RESULTS: Cronbach's alpha coefficient for
      the 'Educational Climate' (EC) global scale was 0.92. In the subscales, the
      'observed' Cronbach's alpha coefficients ranged between 0.57 and 0.79 and were
      higher than the 'expected' ones; except for the Social subscale. In the DREEM
      questionnaire, all of the corrected correlation coefficients between the items
      and the EC global scale, and the items and their corresponding subscales, were
      >0.2; except for items 50 and 17. All goodness-of-fit indices of confirmatory
      factor analysis showed acceptable values (close to one or zero, depending on the
      case), and there was consistency in the results. CONCLUSIONS: The Spanish
      language version of the DREEM questionnaire is a reliable and valid instrument
      for analysing the EC for dental students and its factor structure is supported by
      the data. Although our findings indicate that the DREEM may be as culturally
      independent as was originally stated, more research should be directed at
      verifying the factor structure in various languages and cultural environments.

PMID- 24330079
TI  - Continuation of deferiprone therapy in patients with mild neutropenia may not
      lead to a more severe drop in neutrophil count.
AB  - Approximately 6% of patients with thalassemia receiving deferiprone develop
      neutropenia. Present practice is to monitor absolute neutrophil count (ANC)
      weekly and to interrupt treatment at the first sign of neutropenia, lest
      continuation lead to progressive neutrophil reduction. In a 6-month study
      evaluating the safety and efficacy of a liquid form of deferiprone in 100
      children, ANC was initially checked weekly for all patients. For individuals
      experiencing mild neutropenia, deferiprone was continued but monitoring was
      increased to daily until resolution. Therapy was to be suspended only if the
      episode was prolonged or if it worsened. Four patients experienced single
      episodes of mild neutropenia, and two others each experienced two episodes. All
      eight episodes resolved within 4-7 d despite continued therapy. (One patient
      later developed agranulocytosis and had treatment terminated.) This study showed
      that not all cases of mild neutropenia during deferiprone therapy develop into
      agranulocytosis, and suggests that many may not be caused by deferiprone.
      Transient declines in ANC to levels defined as neutropenic are common even in
      healthy individuals, particularly children; and it could be that the frequent
      monitoring of ANC mandated during deferiprone therapy may reveal cases of
      transient neutropenia that would otherwise have gone undetected and resolved on
      their own without clinical consequences. In patients with thalassemia, several
      factors increase the probability of a transient fall in ANC. These findings raise
      the question of whether deferiprone should be routinely stopped in cases of mild
      neutropenia, provided that such patients have their ANC monitored more frequently
      during the neutropenic episode. 

PMID- 24330080
TI  - Towards a national program to combat neural tube defects in Iraq.

PMID- 24330081
TI  - Enhanced nicotinic receptor mediated relaxations in gastroesophageal muscle
      fibers from Barrett's esophagus patients.
AB  - BACKGROUND: Increased nicotinic receptor mediated relaxation in the
      gastroesophageal antireflux barrier may be involved in the pathophysiology of
      reflux. This study is designed to determine whether the defects we previously
      identified in gastroesophageal reflux disease patients in- vivo are due to
      abnormalities of the gastric sling, gastric clasp, or lower esophageal circular
      (LEC) muscle fibers. METHODS: Muscle strips from whole stomachs and esophagi were
      obtained from 16 normal donors and 15 donors with histologically proven Barrett's
      esophagus. Contractile and relaxant responses of gastric sling, gastric clasp, or
      LEC fibers were determined to increasing concentrations of carbachol and to
      nicotine after inducing maximal contraction to bethanechol. Muscarinic receptor
      density was measured using subtype selective immunoprecipitation. KEY RESULTS:
      Barrett's esophagus gastric sling and LEC fibers have decreased carbachol-induced
      contractions. Barrett's esophagus sling fibers have decreased M2 -muscarinic
      receptors and LEC fibers have decreased M3 receptors. Relaxations of all three
      fiber types are greater in Barrett's esophagus specimens to both high carbachol
      concentrations and to nicotine following bethanechol precontraction. The maximal
      response to bethanechol is greater in Barrett esophagus sling and LEC fibers.
      CONCLUSIONS & INFERENCES: The increased contractile response to bethanechol in
      Barrett's specimens indicates that the defect is likely not due to the smooth
      muscle itself. The enhanced nicotinic receptor mediated response may be involved
      in greater relaxation of the muscles within the high-pressure zone of the
      gastroesophageal junction during transient lower esophageal sphincter relaxations
      and during deglutitive inhibition and may be involved in the pathophysiology of
      gastroesophageal reflux disease.

PMID- 24330082
TI  - Sequence-based identification, genotyping and EUCAST antifungal susceptibilities
      of Trichosporon clinical isolates from Greece.
AB  - Trichosporon yeasts constitute emerging pathogens, implicated in organ-specific
      and systemic infections. In this first, comprehensive study of Trichosporon
      clinical isolates in Greece, 42 isolates were identified by sequencing the
      hypervariable D1/D2 domain of the Large Subunit (LSU) rDNA gene, while
      Trichosporon asahii were genotyped by sequencing the Intergenic Spacer 1 region,
      and antifungal susceptibilities were determined by the EDef 7.2 (EUCAST) method,
      in parallel with the CLSI standard. Trichosporon asahii was the primary species
      (37 isolates) followed by Trichosporon coremiiforme, Trichosporon dermatis,
      Trichosporon loubieri and Trichosporon mycotoxinivorans. One strain remained
      unidentified. Seven T. asahii genotypes were recorded. The major genotypes were:
      genotypes 4 (29%) and 3 (26%) followed by 1, 5 and 7 (9.5% each). Two novel
      genotypes were identified designated as 10 and 11. EUCAST MIC >=2 mg/L was
      recorded in 58% of the isolates (amphotericin B), 41% (itraconazole), 41%
      (posaconazole) and 38% (voriconazole). Fluconazole MICs of >=32 mg/L were
      recorded in 23.8% of the isolates. Analysis of variance performed on absolute
      values showed that the amphotericin B, itraconazole, posaconazole and
      voriconazole MICs of T. asahii were equivalent. Typically higher MIC values were
      displayed by fluconazole. Antifungal susceptibilities of the seven different
      genotypes were homogeneous. Agreements between EUCAST and CLSI ranged from 88.1
      to 97.62%. Overall, the high MICs recorded among the Trichosporon isolates for
      all tested drugs justify routine susceptibility testing of clinical isolates. 

PMID- 24330083
TI  - Breast cancer and dietary patterns: a systematic review.
AB  - This systematic review collates research on the topic of dietary patterns and
      breast cancer risks. The literature search targeted epidemiological studies
      published up to December 2012 and was conducted using the Medline (U.S. National
      Library of Medicine, Bethesda MD, USA) and Lilacs (Latin American and Caribbean
      Health Sciences, Sao Paulo, Brazil) databases. The following search terms were
      used: breast cancer, breast neoplasm, breast carcinoma, diet, food, eating
      habits, dietary patterns, factor analysis, and principal component analysis. Only
      studies that used factor analysis techniques and/or principal component analysis
      were eligible, and a total of 26 studies were included. The findings of these
      studies suggest the Mediterranean dietary pattern and diets composed largely of
      vegetables, fruit, fish, and soy are associated with a decreased risk of breast
      cancer. There was no evidence of an association between traditional dietary
      patterns and risk of breast cancer, and only one study showed a significant
      increase in risk associated with the Western dietary pattern. Diets that include
      alcoholic beverages may be associated with increased risk. 

PMID- 24330085
TI  - Structural findings and molecular modeling approach of a TFPI-like inhibitor.
AB  - Specific blood coagulation inhibitors from hematophagous organisms, with
      different structures and novel mechanism of action, have been described and they
      represent promising agents for the treatment of a variety of human diseases
      related to coagulation and cancer. In our lab, the salivary glands transcriptome
      of the adult Amblyomma cajennense tick was previously characterized by expressed
      sequence tags (EST). A transcript that codes for a tissue factor pathway
      inhibitor (TFPI)-like protein with unique structure was found, and the
      recombinant form of this protein was named Amblyomin-X. This protein was able to
      inhibit the factor Xa amidolytic activity and the activation of factor X by the
      extrinsic tenase complex (FVIIa/TF). Herein, it was performed functional and
      structural evaluation of Amblyomin-X. The CD assay and molecular dynamics
      simulations revealed that Amblyomin-X is structurally stable and the naturally
      unfolded regions as well as the presence of three disulfide bridges in its Kunitz
      type domain seem to sustain its inhibitory activity. Regarding the electrostatic
      potential mapping on the Kunitz-type region, the pattern of charged residues was
      not quite the same in comparison to human TFPI-1 and TFPI-2, pointing out there
      might be distinct functional and structural features, which are going to be
      experimentally exploited. 

PMID- 24330086
TI  - Job strain and obesity.

PMID- 24330084
TI  - A mechanistic look at the effects of adversity early in life on cardiovascular
      disease risk during adulthood.
AB  - Early origins of adult disease may be defined as adversity or challenges during
      early life that alter physiological responses and prime the organism to chronic
      disease in adult life. Adverse childhood experiences or early life stress (ELS)
      may be considered a silent independent risk factor capable of predicting future
      cardiovascular disease risk. Maternal separation (MatSep) provides a suitable
      model to elucidate the underlying molecular mechanisms by which ELS increases the
      risk to develop cardiovascular disease in adulthood. The aim of this review is to
      describe the links between behavioural stress early in life and chronic
      cardiovascular disease risk in adulthood. We will discuss the following: (i)
      adult cardiovascular outcomes in humans subjected to ELS, (ii) MatSep as an
      animal model of ELS as well as the limitations and advantages of this model in
      rodents and (iii) possible ELS-induced mechanisms that predispose individuals to
      greater cardiovascular risk. Overall, exposure to a behavioural stressor early in
      life sensitizes the response to a second stressor later in life, thus unmasking
      an exaggerated cardiovascular dysfunction that may influence quality of life and
      life expectancy in adulthood. 

PMID- 24330087
TI  - Modified elephant trunk technique for chronic aortic dissection: the "double
      elephant trunk".
AB  - The most widely used technique for chronic dissection of the aortic arch and
      thoracoabdominal aorta is the "elephant trunk" (ET). A technique, in which an
      original modification of the ET technique was necessary to avoid visceral
      malperfusion due to the obliteration of the patent false lumen from where
      splanchnic arteries arose, is presented.

PMID- 24330088
TI  - Acne inversa-like lesions associated with the multi-kinase inhibitor sorafenib.

PMID- 24330090
TI  - The 3rd international conference on reproductive immunology in Shanghai:
      September 27-29, 2013. Shanghai, China.
AB  - PROBLEM: After the first and second international conferences on reproductive
      immunology held by Dr. DaJin Li in Shanghai, the related investigators all over
      the world hope to get together to share their latest findings with each other.
      METHOD OF STUDY: Drs. DaJin Li and MeiRong Du sponsored and organized the third
      international conference on reproductive immunology at the Obstetrics and
      Gynecology Hospital affiliated with Fudan University, Shanghai, China, in the
      autumn of 2013. RESULTS: This congress brought together more than 100
      International and National investigators representing a wide range of scientific
      disciplines. All the investigators actively work on reproductive immunology using
      human or large and small animal models. A range of reproductive immunological
      topics including the maternal-fetal immune regulation, reproductive tract mucosal
      immunology, immunocontraception, and pregnancy complications were highlighted and
      discussed in this conference. CONCLUSION: This conference supplied a good
      platform for the international reproductive immunologists to exchange their
      latest study progression and discuss the development direction of reproductive
      immunology in the near future.

PMID- 24330089
TI  - Thiazolidinedione use is associated with improved all-cause mortality compared
      with sulfonylureas among diabetic hemodialysis patients.

PMID- 24330091
TI  - Successful unrelated umbilical cord blood transplantation for class 3 beta
      thalassemia major using a reduced-toxicity regimen.
AB  - Unrelated umbilical CB transplant for class 3 beta-thalassemia major is
      associated with an increased risk of mortality and non-engraftment. We describe
      two patients who underwent successful unrelated umbilical CB transplant using a
      novel reduced-toxicity preparative regimen. This regimen may be sufficiently
      immunosuppressive and myeloablative to ensure engraftment with reduced risks of
      toxicity and mortality. Close monitoring of HHV-6 viral load is advised for
      patients undergoing transplant with this regimen.

PMID- 24330092
TI  - Mechanisms of selective laser trabeculoplasty: a review.
AB  - Selective laser trabeculoplasty is a safe and effective treatment for glaucoma,
      with greater cost effectiveness than its pharmacological and surgical
      alternatives. Nevertheless, although the basic science literature on selective
      laser trabeculoplasty continues to grow, there remains uncertainty over the
      mechanism by which laser trabeculoplasty reduces intraocular pressure. To address
      this uncertainty, the evidence behind several potential biological and mechanical
      mechanisms of selective laser trabeculoplasty were reviewed. In particular,
      cytokine secretion, matrix metalloproteinase induction, increased cell division,
      repopulation of burn sites and macrophage recruitment were discussed. Refining
      our understanding of these mechanisms is essential both to understanding the
      pathophysiology of ocular hypertension and developing improved therapies to treat
      the condition. 

PMID- 24330093
TI  - Effect of probiotics on biomarkers of cardiovascular disease: implications for
      heart-healthy diets.
AB  - The objectives of this article are to review clinical trials that have examined
      the effects of probiotics on low-density lipoprotein cholesterol (LDL-C) and to
      assess the potential of probiotic intake as a therapeutic lifestyle change (TLC)
      dietary option. Twenty-six clinical studies and two meta-analyses are reviewed.
      Significant LDL-C reductions were observed for four probiotic strains:
      Lactobacillus reuteri NCIMB 30242, Enterococcus faecium, and the combination of
      Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12. Two synbiotics, L.
      acidophilus CHO-220 plus inulin and L. acidophilus plus fructo-oligosaccharides,
      also decreased LDL-C. Of the probiotics examined, L. reuteri NCIMB 30242 was
      found to best meet TLC dietary requirements by 1) significantly reducing LDL-C
      and total cholesterol, with robustness similar to that of existing TLC dietary
      options, 2) improving other coronary heart disease risk factors, such as
      inflammatory biomarkers, and 3) having "generally recognized as safe" (GRAS)
      status. Based on these results, the probiotic L. reuteri NCIMB 30242 is a viable
      candidate both for future TLC dietary studies and as a potential option for
      inclusion in TLC dietary recommendations.

PMID- 24330094
TI  - Medication errors outside healthcare facilities: a national poison centre
      perspective.
AB  - Medication errors (ME) are a major concern to healthcare systems. Most studies
      evaluated ME occurring in healthcare facilities; only few focused on ME outside
      them. The objective was to characterise ME occurring outside healthcare
      facilities. A prospective observational follow-up study evaluating all ME
      occurring outside healthcare facilities reported to a national poison information
      centre during a 5-month period. For each ME case, a detailed questionnaire was
      filled and a follow-up call was made within 7 days. The collected data included
      demographics, circumstances, type of error and outcome. Of 1381 consecutive ME
      cases were included; 97.8% involved a single incident and 88.3% one drug. The
      main characteristics of the ME were as follows: children younger than 6 years old
      (58.9%), parents responsible for 55.6% of cases, wrong dose 34.5% and different
      medication 30.1%. Analgesics (27.4%) and antimicrobials (12.2%) were the most
      common pharmaceuticals. The main reasons for the ME were look-alike packaging
      (31.4%) and misunderstood instructions (28%). Most followed up patients (97.1%)
      were asymptomatic or mildly affected; there was one severe case and no mortality.
      Most ME occurring outside healthcare facilities are single incidents, involving
      young children who were administered a wrong dose or medication due to look-alike
      packaging or misunderstood instructions with asymptomatic or mild outcome.
      Improved packaging, labelling and patient education are suggested to reduce ME.

PMID- 24330095
TI  - Carers' quality of life and experiences of adult social care support in England.
AB  - Informal carers make a vital contribution to the well-being of the people they
      care for or look after. Against the policy background in England, the purpose of
      this study was to explore the views of carers who are in contact with adult
      social care support services. A qualitative study with 31 carers, who were
      recruited via local authorities and carers' organisations, was conducted between
      April and July 2012 to collect data on carers' experiences and perceptions of
      their quality of life (QoL) with and without adult social care and support for
      themselves or the person they look after. Through framework analysis, three key
      themes were identified: (i) definitions of social care services 'for' the carer
      or 'for' care recipient and social care outcomes; (ii) carers' access to social
      care services; and (iii) the meaning and value of informal care. We find that
      carers' QoL is affected by social care support directed at carers and support
      directed at those they care for, as well as access to services, the experience of
      stigma in communities, and in how individual needs and preferences are considered
      when making decisions about care. While there is much to welcome in the direction
      of policy in England, this study has shown that there are some gaps in thinking
      around these areas that will need to be addressed if the lives of carers are to
      be improved. 

PMID- 24330096
TI  - Oxygen distribution in proteins defines functional significance of the genome and
      proteome of the malaria parasite Plasmodium falciparum 3D7.
AB  - Although GlaxoSmithKline is on the way to launch the new vaccine candidate 'RTS,
      S', the search for suitable antimalarial drugs still remains an exceeding
      challenge because Plasmodium falciparum-mediated malaria is one of the most
      lethal diseases in the world. Novel innovative ideas are required to identify new
      potential molecular targets to be able to fight this lethal parasite efficiently.
      We used an unconventional bioinformatics approach to analyze the entire genome
      and proteome of the Pf3D7 strain. Because the oxygen (O-) content is a decisive
      parameter that determines the function of a protein, we analyzed the entire Pf3D7
      proteome based on O-containing amino acid expression. Our data disclose a total
      of four proteins encoded by chromosome (Chr)-4 and Chr-9 that have an outstanding
      O-controlled character. The identification of the biological significance of
      these proteins could eventually lead to new vital drug targets.

PMID- 24330097
TI  - The ROS-induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF-1alpha
      in the NCI60 cancer cell lines.
AB  - Intravenous application of high-dose ascorbate is used in complementary
      palliative medicine to treat cancer patients. Pharmacological doses of ascorbate
      in the mM range induce cytotoxicity in cancer cells mediated by reactive oxygen
      species (ROS), namely hydrogen peroxide and ascorbyl radicals. However, little is
      known about intrinsic or extrinsic factors modulating this ascorbate-mediated
      cytotoxicity. Under normoxia and hypoxia, ascorbate IC50 values were determined
      on the NCI60 cancer cells. The cell cycle, the influence of cobalt chloride
      induced hypoxia-inducible factor-1alpha (HIF-1alpha) and the glucose transporter
      1 (GLUT-1) expression (a pro-survival HIF-1alpha-downstream-target) were analysed
      after ascorbate exposure under normoxic and hypoxic conditions. The amount of
      ascorbyl radicals increased with rising serum concentrations. Hypoxia (0.1% O2 )
      globally increased the IC50 of ascorbate in the 60 cancer cell lines from 4.5 +/-
      3.6 mM to 10.1 +/- 5.9 mM (2.2-fold increase, P < 0.001, Mann-Whitney t-test),
      thus inducing cellular resistance towards ascorbate. This ascorbate resistance
      depended on HIF-1alpha-signalling, but did not correlate with cell line-specific
      expression of the ascorbate transporter GLUT-1. However, under normoxic and
      hypoxic conditions, ascorbate treatment at the individual IC50 reduced the
      expression of GLUT-1 in the cancer cells. Our data show a ROS-induced, HIF-1alpha
      and O2 -dependent cytotoxicity of ascorbate on 60 different cancer cells. This
      suggests that for clinical application, cancer patients should additionally be
      oxygenized to increase the cytotoxic efficacy of ascorbate.

PMID- 24330098
TI  - Myeloperoxidase in chronic kidney disease: role of visceral fat.
AB  - AIM: Visceral fat is more significantly correlated with inflammation markers and
      oxidative stress than is subcutaneous fat. Myeloperoxidase is one inflammatory
      signal secreted after polymorphonuclear leukocytes are stimulated. However, few
      studies discuss the correlation between visceral fat and the inflammatory
      response in patients with chronic kidney disease (CKD). METHODS: Sixty-six
      patients with CKD were enrolled and 60 healthy participants. Visceral fat levels
      were obtained using bioelectrical impedance analysis. Traditional risk factors
      for myeloperoxidase were analyzed. RESULTS: Baseline myeloperoxidase levels were
      significantly different between patients and controls, and were correlated with
      visceral fat after they had been adjusted for residual renal function. A
      multivariate linear regression model revealed that the neutrophil count and
      visceral fat and serum albumin levels were significant predictors of plasma
      myeloperoxidase in patients with CKD, but not in controls. The neutrophil count
      was correlated with myeloperoxidase only in the CKD group. CONCLUSION: Visceral
      fat predicted plasma myeloperoxidase in patients with CKD, but not in healthy
      controls. Myeloperoxidase was probably contributed by primed and activated
      neutrophils that had been irritated by visceral fat in patients with CKD.

PMID- 24330099
TI  - Does mechanical bowel preparation ameliorate damage from rectal injury in radical
      prostatectomy? Analysis of 151 rectal injury cases.
AB  - OBJECTIVE: To evaluate whether mechanical bowel preparation before radical
      prostatectomy ameliorates damage from rectal injury in radical prostatectomy.
      METHODS: Among 35,099 radical prostatectomy cases in the Japanese Diagnosis
      Procedure Combination database 2007-2012, those where a rectal injury occurred
      were stratified into a preoperative mechanical bowel preparation group
      (polyethylene glycol electrolyte, magnesium citrate solution and sodium
      picosulfate) and a non-mechanical bowel preparation group. The associations
      between mechanical bowel preparation and rectal injury were evaluated by
      multivariate regression analysis for: (i) subsequent infectious complications;
      (ii) requirement of delayed colostomy formation after primary closure; (iii)
      postoperative length of stay; and (iv) total costs. Covariates were age, surgical
      approach, Charlson Comorbidity Index, T and N category, hospital volume, hospital
      academic status, and colostomy formation. RESULTS: Overall, 151 rectal injury
      cases (0.43%) were identified. Of those, 73 patients (48%) received mechanical
      bowel preparation. Multivariate analyses showed that all four outcomes were not
      statistically different between mechanical bowel preparation and non-mechanical
      bowel preparation groups (infectious complication rate: 12% vs 10%, P = 0.80;
      delayed colostomy rate: 21% vs 31%, P = 0.34; length of stay: 28 vs 30 days, P =
      0.84; and total costs: $24,665 vs $23,837, P = 0.81). CONCLUSION: Our analysis
      did not detect a beneficial impact of mechanical bowel preparation on
      perioperative morbidity associated with rectal injury during radical
      prostatectomy. This finding suggests that mechanical bowel preparation might be
      safely omitted before radical prostatectomy.

PMID- 24330100
TI  - Chocolate is good for me, right?

PMID- 24330101
TI  - Counting platelets at transfusion threshold levels: impact on the decision to
      transfuse. A BEST Collaborative - UK NEQAS(H) International Exercise.
AB  - BACKGROUND AND OBJECTIVES: Obtaining accurate and precise platelet enumeration in
      automatic platelet analysers at low platelet counts is a challenge. To explore
      the performance of current haematology analysers in counting platelet
      concentrations usually used as platelet transfusion threshold. MATERIAL AND
      METHODS: An international exercise where four blood samples with platelet levels
      near usual platelet transfusion thresholds was prepared and distributed. RESULTS:
      The samples shipped had a platelet count of 6.3, 13.3, 21.6 and 53.0 * 10(9) /l
      according to the international reference method. We received 82 sets of results
      from nine countries. Instruments from six different manufacturers were
      represented. Although the mean count for each of the four samples was very
      similar to the values, according to the reference method (9.0, 16.2, 23.0 and
      57.6 * 10(9) /l), significant variability in the results was found. Assuming that
      these were patient samples and the result of the count used to indicate a
      prophylactic platelet transfusion, undertransfusion would have occurred for 24.5%
      of the LP1 samples at a transfusion threshold of 10 * 10(9) /l and, at a
      threshold of 20 * 10(9) /l, undertransfusion would have occurred for 7.2% of the
      LP1 and 16.2% of the LP2 samples and overtransfusion would have occurred with
      23.1% of the LP3 samples. CONCLUSION: The results suggest that significant
      inaccuracy exists in counting low levels of platelets and that this inaccuracy
      might have a significant impact in under- and overtransfusion of platelet
      concentrates to patients.

PMID- 24330102
TI  - Transcriptome analyses suggest a disturbance of iron homeostasis in soybean
      leaves during white mould disease establishment.
AB  - Sclerotinia sclerotiorum is a serious pathogen of numerous crops around the
      world. The major virulence factor of this pathogen is oxalic acid (OA). Mutants
      that cannot produce OA do not cause disease, and plants that express enzymes that
      degrade OA, such as oxalate oxidase (OxO), are very resistant to S. sclerotiorum.
      To examine the effect of OA on plants, we infiltrated soybean leaves with 5 mm OA
      and examined the gene expression changes at 2 h post-infiltration. By comparing
      the gene expression levels between leaves of a transgenic soybean carrying an OxO
      gene (OxO) and its parent AC Colibri (AC) infiltrated with OA (pH 2.4) or water
      (pH 2.4 or 5.5), we were able to compare the effects of OA dependent or
      independent of its pH. Gene expression by microarray analysis identified 2390
      genes that showed changes in expression, as determined using an overall F-test P
      value cut-off of 0.001. The additional requirement that at least one pairwise t
      test false discovery rate (FDR)-corrected P value should be less than 0.001
      reduced the list of the most highly significant differentially expressed genes to
      1054. Independent of pH, OA altered the expression levels of 78 genes, with
      ferritin showing the strongest induction by OA. The combination of OA plus its
      low pH caused 1045 genes (99% of all significant genes) to be differentially
      expressed, with many of the up-regulated genes being related to basal defence,
      such as genes of the phenylpropanoid pathway and various cytochrome P450s. RNA
      seq was also conducted on four samples: OxO and AC genotypes infiltrated with
      either OA pH 2.4 or water pH 2.4. The RNA-seq analysis also identified ferritin
      paralogues as being strongly induced by OA. As the expression of ferritin, a gene
      that encodes for an iron storage protein, is induced by free iron, these results
      suggest that S. sclerotiorum benefits from the ability of OA to free iron from
      plant proteins, as this induces host cell death, and also allows the uptake and
      assimilation of the iron for its own metabolic needs. 

PMID- 24330103
TI  - Prevalence and risk factors for pulmonary hypertension in patients with
      hemoglobin E/beta-thalassemia disease.
AB  - OBJECTIVES: To find the prevalence and risk factors of pulmonary hypertension
      (PHT) in adult patients with hemoglobin E/beta-thalassemia disease (E/beta-Thal).
      METHODS: One hundred and ten clinically stable E/beta-Thal outpatients, sixty-one
      of whom had undergone splenectomy, were prospectively studied using their
      clinical profiles, selected blood tests, chest roentgenogram, and transthoracic
      echocardiogram. Based on the pulmonary artery systolic pressure (PASP) values
      estimated by the echocardiogram of >=36 mmHg, they were dichotomized into those
      with (PHT+) and without (PHT-) PHT. RESULTS: PHT was found in 41 (37.3%) patients
      without gender preponderance. It was not due to the left heart and was not severe
      (PASP = 46.3 +/- 10.4 mmHg). PASP was higher in splenectomized patients (48.0 +/-
      11 vs. 40.3 +/- 4.7 mmHg (P = 0.004)). PHT was found in 32 of 61 (52.5%)
      splenectomized patients, mostly (53%) in the second decade, and rarely (6.3%)
      during the first 5 yr after splenectomy. PHT+ patients had more hemolysis (P =
      0.001-0.04 depending on the parameters), more asplenic cases (P < 0.001), and
      higher serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and high
      sensitivity C-reactive protein levels (P = 0.004 and 0.008, respectively). Strong
      risk factors by univariate analysis were serum sVCAM-1 levels >=1600 ng/mL, serum
      cell-free Hb >= 3 mg/dL, asplenia, and amount of NRBCs/100 WBCs >40. CONCLUSIONS:
      Prevalence of PHT in E/beta-Thal patients was 37.3% without gender preponderance.
      Those with severe hemolysis and asplenia invariably had severer PHT. Strong risk
      factors were asplenia and associated markedly elevated values of sVCAM-1, cell
      free Hb, and NRBCs in blood.

PMID- 24330104
TI  - Sulfate availability affects ABA levels and germination response to ABA and salt
      stress in Arabidopsis thaliana.
AB  - Sulfur-containing compounds play a critical role in the response of plants to
      abiotic stress factors including drought. The phytohormone abscisic acid (ABA) is
      the key regulator of responses to drought and high-salt stress. However, our
      knowledge about interaction of S-metabolism and ABA biosynthesis is scarce. Here
      we report that sulfate supply affects synthesis and steady-state levels of ABA in
      Arabidopsis wild-type seedlings. By using different mutants of the sulfate uptake
      and reduction pathway, we confirmed the impact of sulfate supply on steady-state
      ABA content in Arabidopsis and demonstrated that this impact was due to cysteine
      availability. Loss of the chloroplast sulfate transporter3;1 function (sultr3;1)
      resulted in significantly decreased aldehyde oxidase (AO) activity and ABA levels
      in seedlings and seeds. These mutant phenotypes could be reverted by exogenous
      application of cysteine or ectopic expression of SULTR3;1. In addition the
      sultr3;1 mutant showed a decrease of xanthine dehydrogenase activity, but not of
      nitrate reductase, strongly indicating that in seedlings cysteine availability
      limits activity of the molybdenum co-factor sulfurase, ABA3, which requires
      cysteine as the S-donor for sulfuration. Transcription of ABA3 and NCED3,
      encoding another key enzyme of the ABA biosynthesis pathway, was regulated by S
      supply in wild-type seedlings. In contrast, ABA up-regulated the transcript level
      of SULTR3;1 and other S-metabolism-related genes. Our results provide evidence
      for a significant co-regulation of S-metabolism and ABA biosynthesis that
      operates to ensure sufficient cysteine for AO maturation and highlights the
      importance of sulfur for stress tolerance of plants. 

PMID- 24330106
TI  - Trending in 2014: Hippocrates.

PMID- 24330107
TI  - The Hippocratic Oath: back to the future?

PMID- 24330108
TI  - Matching the practical implementation of education with medical profession
      values.

PMID- 24330109
TI  - Avoiding polypharmacy and therapeutic nihilism in medical training in poor
      countries.

PMID- 24330110
TI  - The professional oath: pledge of allegiance or reflective practice?

PMID- 24330111
TI  - Avoiding the trap of overtreatment.

PMID- 24330112
TI  - When Hippocrates and Sun Simiao met in Taiwan in a highly efficient health care
      system.

PMID- 24330113
TI  - Do no harm: is it time to rethink the Hippocratic Oath?
AB  - INTRODUCTION: The 1964 revision of the Hippocratic Oath addressed the
      disconnection in language and context between the classical doctrine and 20th
      century medicine. Now, 50 years later, we argue that any revision of the Oath
      must be responsive to the significant social, technical and political changes
      that have occurred in health care. THE CONTEXT FOR THE HIPPOCRATIC OATH: This
      paper examines the ways in which health care and the health professions have
      changed over the last half-century and describes a range of environmental and
      contextual features that expose the inadequacies of the 1964 Oath in the worlds
      of today and the future. We note the constancy of the doctor-patient dyad in
      contemporary ethical codes and consider from the perspective of patient safety
      those aspects of care that might fall short of the optimum if the focus on the
      doctor is retained. We ask whether there is any merit in maintaining a focus on
      the ethics or professionalism of doctors, or whether more of our attention should
      be directed towards the ethics of health care itself. CONCLUSIONS: Patient safety
      is widely acknowledged as a major health issue. Being open about the
      interdependency of doctors, the complex socio-political nature of health care,
      and the inevitability of errors and adverse events need not challenge the
      authority of the doctor. Rather, openness about both the ways in which medicine
      has changed and the harms that doctors may (inadvertently) cause might afford
      medicine the opportunity to build a different relationship with patients (and
      with society more broadly), that recognises complexity, human fallibility and the
      uncertainty of medicine.

PMID- 24330114
TI  - Does technology help doctors to access, use and share knowledge?
AB  - CONTEXT: Given the power and pervasiveness of technology, this paper considers
      whether it can help doctors to access, use and share knowledge and thus
      contribute to their ability to uphold the part of the Hippocratic Oath concerned
      with respecting 'the hard-won scientific gains of those physicians in whose steps
      I walk' and sharing 'such knowledge as is mine with those who are to follow'. How
      technology supports connections between doctors and knowledge is considered by
      focusing on the use of mobile technology in the workplace and Web 2.0 tools.
      METHODS: Sfard's 'acquisition' and 'participation' models are employed to help
      develop an understanding of what these uses of technology mean for learning and
      knowledge sharing. DISCUSSION: The employment of technology is not neutral in its
      effects. Issues relate to knowledge ownership, information overload, quality
      control and interpretations attached to the use of mobile devices in the
      workplace. These issues raise deeper questions about the nature of knowledge and
      social theory and socio-material research questions about the effect of
      technology on workplace learning. CONCLUSION: Although the empirical and
      theoretical evidence presented shows how technology has clear potential to
      contribute both to accessing evidence and sharing knowledge, there is need for
      further research that applies theoretical frameworks to the analysis of the
      impact of technology on workplace learning.

PMID- 24330115
TI  - The twin traps of overtreatment and therapeutic nihilism in clinical practice.
AB  - CONTEXT: The modern version of the Hippocratic Oath requires doctors to swear
      that they will apply, for the benefit of the sick, all measures that are
      required, avoiding the twin traps of overtreatment and therapeutic nihilism. This
      paper explores the magnitude of the problem of overtreatment and undertreatment
      and the potential sources of these treatment errors. METHODS: We undertook a
      narrative review of the literature on errors in treatment associated with flaws
      in doctors' judgements and present evidence from research into clinical reasoning
      and from psychological research into decision making. Based on evidence from
      these two research fields, we explored the possible reasons why doctors
      erroneously withhold or unnecessarily administer treatments. RESULTS: Variation
      in treatment has been documented, even with similar clinical presentations under
      a variety of conditions, suggesting that overtreatment and undertreatment
      actually occur, with adverse effects for patients. Both types of error have been
      demonstrated, even when the doctor arrived at the correct diagnosis. They may be
      associated with the influence exerted on doctors' treatment judgements by factors
      that are unrelated to the specific problem, such as patients' socio-demographic
      characteristics and the doctor's practice culture. Doctors are also subject to
      commission bias and to omission bias, which have been demonstrated to occur in
      several domains. Such biases lead doctors to administer unnecessary treatments or
      to withhold required treatments due to anticipated regret. Little is known about
      cognitive processes underlying doctors' treatment decisions, but mental
      representations of diseases that provide the basis for diagnostic reasoning are
      also probably used for treatment judgements. CONCLUSIONS: Doctors are at risk of
      falling into the twin traps of overtreatment and therapeutic nihilism. Further
      research should explore how to avoid these traps, but it may require deliberate
      reflection on problems to be solved to counteract the influence of factors that
      are beyond the patient's problem.

PMID- 24330116
TI  - Sociomateriality in medical practice and learning: attuning to what matters.
AB  - CONTEXT: In current debates about professional practice and education, increasing
      emphasis is placed on understanding learning as a process of ongoing
      participation rather than one of acquiring knowledge and skills. However,
      although this socio-cultural view is important and useful, issues have emerged in
      studies of practice-based learning that point to certain oversights. METHODS:
      Three issues are described here: (i) the limited attention paid to the importance
      of materiality - objects, technologies, nature, etc.-- in questions of learning;
      (ii) the human-centric view of practice that fails to note the relations among
      social and material forces, and (iii) the conflicts between ideals of evidence
      based standardised models and the sociomaterial contingencies of clinical
      practice. DISCUSSION: It is argued here that a socio-material approach to
      practice and learning offers important insights for medical education. This view
      is in line with a growing field of research in the materiality of everyday life,
      which embraces wide-ranging families of theory that can be only briefly mentioned
      in this short paper. The main premise they share is that social and material
      forces, culture, nature and technology, are enmeshed in everyday practice.
      Objects and humans act upon one another in ways that mutually transform their
      characteristics and activity. Examples from research in medical practice show how
      materials actively influence clinical practice, how learning itself is a material
      matter, how protocols are in fact temporary sociomaterial achievements, and how
      practices form unique and sometimes conflicting sociomaterial worlds, with
      diverse diagnostic and treatment approaches for the same thing. CONCLUSIONS: This
      discussion concludes with implications for learning in practice. What is required
      is a shift from an emphasis on acquiring knowledge to participating more wisely
      in particular situations. This focus is on learning how to attune to minor
      material fluctuations and surprises, how to track one's own and others' effects
      on 'intra-actions' and emerging effects, and how to improvise solutions.

PMID- 24330117
TI  - Humility and respect: core values in medical education.
AB  - CONTEXT: Many of the values and behaviours described in the original Hippocratic
      Oath are relevant to medical education. In particular, the values of intellectual
      humility and respect for one's colleagues are essential in all scientific
      disciplines. There are three contexts within medical education from which to
      consider humility and respect: uncertainty; theory, and colleagues. UNCERTAINTY:
      As medical education grows in scope and participation, we will be required to
      acknowledge that we 'know not' with increasing frequency. The uncertainty of what
      we do and do not know is compounded by uncertainty about whether ignorance is
      individual or corporate. As difficult as it is to admit that we 'know not', it is
      dangerous NOT to recognise the limits of our knowledge and experience. THEORY:
      Theories are critical tools in understanding complex phenomena. They identify
      constructs and relationships that are important and those that are irrelevant. We
      tend to forget that theories are models or simplified representations of reality
      and not in themselves 'truths'. Viewing problems from other theoretical
      perspectives can widen our horizons by allowing us to identify possibly important
      concepts and relationships that we have not considered. COLLEAGUES: Colleagues
      are invaluable for helping us respond to our 'knowing not' and for providing
      alternative perspectives when our theories lead us astray. However, colleagues
      come in many guises and include close colleagues, as well as those in distant
      fields. OBSTACLES TO HUMILITY AND RESPECT: As obviously desirable as humility and
      respect seem to be, there are conflicts that prevent us from being humble and
      respectful. Such conflicts include other salient professional values, such as
      critical scepticism, competition and confidence. HONOURING THE OATH: Adoption of
      the values of humility and respect in medical education can be fostered through
      intentional behaviours, both as individuals and as a discipline. We can
      deliberately seek to broaden our horizons to promote intellectual humility. We
      can foster collaboration among colleagues who come from different places, both
      geographically and intellectually. Finally, we can pursue 'academic cultural
      exchanges' with other fields and disciplines to learn and share in different ways
      of thinking.

PMID- 24330118
TI  - Palliative care education in U.S. medical schools.
AB  - CONTEXT: Medical educators in the U.S.A. perceive the teaching of palliative care
      competencies as important, medical students experience it as valuable and
      effective, and demographic and societal forces fuel its necessity. Although it is
      encouraged by the Association of American Medical Colleges, the only palliative
      care-related mandate in U.S. medical schools is the Liaison Committee on Medical
      Education directive that end-of-life (EoL) care be included in medical school
      curricula, reinforcing the problematic conflation of EoL and palliative care.
      FINDINGS: A review of US medical school surveys about the teaching of palliative
      and EoL care reveals varied and uneven approaches, ranging from 2 hours in the
      classroom on EoL to weeks of palliative care training or hospice-based clinical
      rotations. IMPLICATIONS: Palliative care competencies are too complex and
      universally important to be relegated to a minimum of classroom time, random
      clinical exposures, and the hidden curriculum. RECOMMENDATIONS: Given the reality
      of overstrained medical school curricula, developmentally appropriate, basic
      palliative care competencies should be defined and integrated into each year of
      the medical school curriculum, taking care to circumvent the twin threats of
      curricular overload and educational abandonment.

PMID- 24330119
TI  - Treating the whole patient: passing time-honoured skills for building doctor
      patient relationships on to generations of doctors.
AB  - OBJECTIVES: This paper aims to honour the Hippocratic Oath in modern practice by
      providing reflections on the development of ways for doctors to know the whole
      person that have accrued over the five decades to the present. METHODS: I present
      a perspective piece, which includes personal reflections and cites relevant
      literature. RESULTS: Powerful role models sustained the concept of knowing the
      whole patient in an era of scientific medicine. Beginning in the 1980s, skills
      allowing ordinary doctors to know the whole patient were made transparent to
      learners in courses and medical school curricula. As we approach the 2020s,
      increasing numbers of doctors have mastered these skills and are teaching them.
      CONCLUSIONS: A modern way of practice is emerging; this emphasises the human side
      of medicine and its rewards, despite barriers such as those imposed by time
      limitations.

PMID- 24330120
TI  - Ensuring high-quality patient care: the role of accreditation, licensure,
      specialty certification and revalidation in medicine.
AB  - CONTEXT: The accreditation of medical school programmes and the licensing and
      revalidation (or recertification) of doctors are thought to be important for
      ensuring the quality of health care. Whereas regulation of the medical profession
      is mandated in most jurisdictions around the world, the processes by which
      doctors become licensed, and maintain their licences, are quite varied. With
      respect to educational programmes, there has been a recent push to expand
      accreditation activities. Here too, the quality standards on which medical
      schools are judged can vary from one region to another. OBJECTIVES: Given the
      perceived importance placed by the public and other stakeholders on oversight in
      medicine, both at the medical school and individual practitioner levels, it is
      important to document and discuss the regulatory practices employed throughout
      the world. METHODS: This paper describes current issues in regulation, provides a
      brief summary of research in the field, and discusses the need for further
      investigations to better quantify relationships among regulatory activities and
      improved patient outcomes. DISCUSSION: Although there is some evidence to support
      the value of medical school accreditation, the direct impact of this quality
      assurance initiative on patient care is not yet known. For both licensure and
      revalidation, some investigations have linked specific processes to quality
      indicators; however, additional evaluations should be conducted across the
      medical education and practice continuum to better elucidate the relationships
      among regulatory activities and patient outcomes. More importantly, the value of
      accreditation, licensure and revalidation programmes around the world, including
      the effectiveness of specific protocols employed in these diverse systems, needs
      to be better quantified and disseminated.

PMID- 24330121
TI  - The 'special obligations' of the modern Hippocratic Oath for 21st century
      medicine.
AB  - CONTEXT: Profound advances and discoveries in medicine have markedly improved the
      lives of many over the 50 years since the modern Hippocratic Oath was written.
      Regrettably, these advances were and continue to be implemented suboptimally and
      inequitably across the globe. 'Special obligations to all my fellow humans' is an
      important theme of the modern Oath. From this perspective, we reflect on the
      special obligations of the medical profession, and examine how these obligations
      have changed over the past 50 years. METHODS: We draw from perspectives of the
      social contract, professionalism, quality improvement, patient safety and a group
      of 31 international colleagues involved in medical education as we examine these
      obligations for individual doctors, health care institutions and medical
      education systems. The perspectives of the 31 clinician-educators helped us to
      situate the meaning of the theme of 'special obligations' in the context of
      challenges facing medical education and health care in the 21st century.
      OBSERVATIONS: Improving the quality of care and patient safety, and reducing
      health care disparities are now paramount as 'special obligations' for doctors,
      health care systems and medical education organisations, and require us to work
      collectively and collaboratively in an increasingly interconnected world. In our
      view, traditions such as the Hippocratic Oath will be worthy of public support
      only when the medical profession demonstrates in meaningful and transparent ways
      that it is meeting its social and civic obligations to make the world, not just
      health care, a better place.

PMID- 24330122
TI  - Updating the Hippocratic Oath to include medicine's social contract.
AB  - CONTEXT: It is widely understood that reciting a contemporary version of the
      Hippocratic Oath has two purposes. It constitutes a public commitment on the part
      of the prospective doctor to preserving the traditional values of the medical
      profession and to meeting the obligations expected of a doctor. It is also an
      important symbolic ritual in the process of professional identity formation.
      METHODS: A portion of the 1964 version of the Hippocratic Oath is examined for
      its relevance to the current practice of medicine. Its closing paragraph reads:
      'If I do not violate this oath, may I enjoy life and art, be respected while I
      live and remembered with affection thereafter. May I always act to preserve the
      finest traditions of my calling and may I long experience the joy of healing
      those who seek my help.' This is interpreted as representing the doctor's
      expectations of the practice of medicine: job satisfaction; status, and prestige.
      It also conveys the understanding that enjoying these benefits is contingent upon
      the doctor's adherence to the terms of the Oath. CONCLUSIONS: Our current
      understanding of the relationship between medicine and society is that a social
      contract exists under which members of the profession are granted a privileged
      position in society on the understanding that they will meet society's reasonable
      expectations. These expectations entail obligations not only to patients and to
      the profession, but to wider society. The Oath under consideration, which
      concentrates on medicine's obligations to patients and to the profession, does
      not adequately reflect its obligations to society. It is suggested that versions
      of the Hippocratic Oath used in the future should be updated to better reflect
      the obligations of both individual doctors and the medical profession to society.

PMID- 24330123
TI  - Modulation of the TRPV1 channel: current clinical trials and recent patents with
      focus on neurological conditions.
AB  - The transient receptor potential vanilloid-1 cat ion channel (TRPV1) is a
      nonspecific cation channel that can be activated by multiple endogenous stimuli
      and is expressed predominantly in sensory neurons, where it serves as a key nodal
      point in pain transmission pathways. In mammals, TRPV1 displays a wide tissue and
      cellular expression including both the peripheral and central nervous system, and
      in the latter it is now recognized to have a broader distribution and function.
      The pharmacological modulation of TRPV1 represents a strategy for the treatment
      of a variety of disease states, particularly those requiring chronic pain
      management. The validation of the TRPV1 channel as a therapeutic target for the
      control of pain and inflammatory conditions in a variety of diseases and injury
      states, has prompted the development of several TRPV1 agonists and antagonists
      that have entered clinical trials. Studies comparing the analgesic effects of
      TRPV1 antagonists with and without significant CNS penetration demonstrated that
      a dual (both peripheral and central) action is required to produce broad-spectrum
      analgesia. TRPV1 can be considered as a target for next generation analgesics.
      However, although a number of compounds are in clinical trials, the therapeutic
      utility of TRPV1 agonist and antagonists is yet to be validated unequivocally.
      This review summarizes current clinical trials and recent patents with small
      molecule TRPV1 agonists and antagonists with a focus on neurological conditions. 

PMID- 24330124
TI  - Cerebrovascular ultrasonography for selecting patients for stroke intervention.
AB  - Currently employed diagnostic ultrasonography provides clinically relevant
      information about cerebral hemodynamic changes in patients with cerebrovascular
      ischemia. The information thus obtained is often helpful to the physician for
      establishing or confirming the diagnosis and prognosis as well as in taking
      appropriate therapeutic decisions. It is associated with a high temporal
      resolution and can be performed bedside for rapid diagnosis as well as prolonged
      monitoring. Transcranial Doppler (TCD) ultrasonography is a non-invasive
      diagnostic modality that provides physiological information regarding various
      intracranial hemodynamic alterations in patients with cerebrovascular ischemia.
      Extended applications of TCD are useful in understanding various
      pathophysiological mechanisms responsible for the clinical manifestations of
      cerebrovascular ischemia. Thus, TCD is aptly called as the 'stethoscope' of a
      stroke neurologist. Cerebrovascular ultrasonography is considered as an essential
      component of a comprehensive stroke center. We have reviewed various recent
      patents pertaining to the applications of cerebrovascular ultrasonography
      employed in the selection of stroke patients for various therapeutic
      interventions. 

PMID- 24330125
TI  - Acute kidney injury after total aortic arch repair with moderate hypothermic
      circulatory arrest.
AB  - BACKGROUND AND AIM: The aim of this study is to evaluate acute kidney injury
      (AKI) after total aortic arch repair (TAR) with moderate hypothermic circulatory
      arrest (MHCA) and selective antegrade cerebral perfusion (SACP). METHODS: A
      retrospective analysis was performed in 200 patients who underwent TAR with HCA
      and SACP between 2008 and 2012. The AKI severity was classified into three grades
      (R=risk, I=injury, F=failure) by RIFLE criteria, and patients who required renal
      replacement therapy were included in grade F. RESULTS: Postoperative AKI was
      observed in 88 patients (44%) including 53 RIFLE-R (27%), 18 RIFLE-I (9%), and 17
      RIFLE-F (9%). Significantly higher 30-day mortality was observed in AKI (+) group
      compared with AKI (-) group (10.2% [9/88] vs. 1.8% [2/112]; p=0.012). The three
      year survival rate was 85% in AKI (+) group and 93% in AKI (-) group, and log
      rank test revealed better survival in AKI (-) group (p=0.022). Multivariate Cox
      proportional-hazards regression detected AKI (all grades) and cardiac arrest time
      as predictors of mid-term mortality (hazard ratio [HR]: 3.2, p=0.041 and HR:
      1.02, p=0.006, respectively). Multivariate analysis revealed prolonged operative
      time (>= 490 min) as an independent risk factor for AKI (all grades), and
      emergency, atrial fibrillation, operative time (>= 490 min), and hypothermia (<24
      degrees C) as risk factors for severe AKI (RIFLE-I and -F). CONCLUSIONS:
      Postoperative AKI stratified by RIFLE criteria was significantly associated with
      short- and mid-term outcomes in TAR with MHCA and SACP.

PMID- 24330126
TI  - Adult ocular adnexal rhabdomyosarcoma presenting with inferior fornix lesion
      without proptosis.

PMID- 24330105
TI  - The cardiokine secreted Frizzled-related protein 3, a modulator of Wnt
      signalling, in clinical and experimental heart failure.
AB  - OBJECTIVES: Experimental studies have shown involvement of Wnt signalling in
      heart failure (HF). We hypothesized that secreted frizzled-related protein 3
      (sFRP3), a modulator of Wnt signalling, is related to the progression of HF.
      DESIGN: Circulating sFRP3 was measured in 153 HF patients and compared with 25
      healthy controls. The association of sFRP3 with mortality was evaluated in 1202
      patients (GISSI-HF trial). sFRP3 mRNA expression was assessed in failing human
      and murine left ventricles (LV), and cellular localization was determined after
      fractioning of myocardial tissue. In vitro studies were carried out in cardiac
      fibroblasts subjected to cyclic mechanical stretch. RESULTS: (i) Heart failure
      patients had significantly raised serum sFRP3 levels compared with controls, (ii)
      during a median follow-up of 47 months, 315 patients died in the GISSI-HF
      substudy. In univariable Cox regression, tertiles of baseline sFRP3 concentration
      were significantly associated with all-cause and cardiovascular mortality. After
      adjustment for demographic and clinical variables, but not for CRP and NT-proBNP,
      the associations with mortality remained significant for the third tertile (all
      cause, HR 1.45, P = 0.011; cardiovascular, HR 1.66, P = 0.003), (iii) sFRP3 mRNA
      expression was increased in failing human LV, with a decline following LV assist
      device therapy. LV from post-MI mice showed an increased sFRP3 mRNA level,
      particularly in cardiac fibroblasts, and (iv) mechanical stretch enhanced sFRP3
      expression and release in myocardial fibroblasts. CONCLUSION: There is an
      association between increased sFRP3 expression and adverse outcome in HF,
      suggesting that the failing myocardium itself contributes to an increase in
      circulating sFRP3.

PMID- 24330127
TI  - Eculizumab reverses the potentially fatal effects of kidney graft reperfusion
      injury.
AB  - Half an hour after reperfusion, the kidney, transplanted to the infant from an
      adult brain dead standard criteria donor, became flabby and acquired blue color.
      Hyperacute rejection was suspected as a consequence of false negative cross
      match, and eculizumab was administered with the purpose to treat antibody
      mediated injury, with fast and clear effect. The patient's blood was tested for
      donor-specific antibodies on the next day, and results were negative. We
      attribute graft damage to reperfusion injury and explain eculizumab's
      effectiveness to its ability to prevent progression of reperfusion injury. 

PMID- 24330129
TI  - Mutation of FVS1, encoding a protein with a sterile alpha motif domain, affects
      asexual reproduction in the fungal plant pathogen Fusarium oxysporum.
AB  - Fusarium oxysporum produces three kinds of asexual spores: microconidia,
      macroconidia and chlamydospores. We previously analysed expressed sequence tags
      during vegetative growth and conidiation in F. oxysporum and found 42 genes that
      were markedly upregulated during conidiation compared to vegetative growth. One
      of the genes, FVS1, encodes a protein with a sterile alpha motif (SAM) domain,
      which functions in protein-protein interactions that are involved in
      transcriptional or post-transcriptional regulation and signal transduction. Here,
      we made FVS1-disrupted mutants from the melon wilt pathogen F. oxysporum f. sp.
      melonis. Although the mutants produced all three kinds of asexual spores with
      normal morphology, they formed markedly fewer microconidia and macroconidia than
      the wild type. The mutants appeared to have a defect in the development of the
      conidiogenesis cells, conidiophores and phialides, required for the formation of
      microconidia and macroconidia. In contrast, chlamydospore formation was
      dramatically promoted in the mutants. The growth rates of the mutants on media
      were slightly reduced, indicating that FVS1 is also involved in, but not
      essential for, vegetative growth. We also observed that mutation of FVS1 caused
      defects in conidial germination and virulence, suggesting that the Fvs1 has
      pleiotropic functions in F. oxysporum.

PMID- 24330128
TI  - Effect of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, on
      measurement of serum 1,5-anhydroglucitol.

PMID- 24330130
TI  - Homocysteine and other cardiovascular risk factors in patients with lichen
      planus.
AB  - BACKGROUND: Chronic inflammation was found to play an important role in the
      development of cardiovascular risk factors. Homocysteine (Hcy) and fibrinogen
      have been identified as a major independent risk factor for cardiovascular
      disease. Lichen planus is assumed to be closely related to dyslipidaemia. Several
      cytokines involved in lichen planus pathogenesis, could explain its association
      with dyslipidaemia. Also chronic inflammation with lichen planus has been
      suggested as a component of the metabolic syndrome. OBJECTIVE: The aim of this
      study was to detect a panel of cardiovascular risk factors in patients of lichen
      planus. PATIENTS AND METHODS: This study was done on 40 patients of lichen planus
      and 40 healthy controls. All patients and controls were subjected to clinical
      examination. Serum levels of homocysteine, fibrinogen and high-sensitive C
      reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay
      technique (ELISA). Metabolic syndrome parameters including anthropometric
      measures, lipid profiles, blood sugar and blood pressure were studied. RESULTS:
      Patients with lichen planus showed significant association with metabolic
      syndrome parameters than controls (P < 0.001). Serum homocysteine, fibrinogen and
      hs-CRP were significantly higher in lichen planus patients than controls (P <
      0.001). Serum homocysteine correlated with both serum hs-CRP and serum
      fibrinogen. However, there was no correlation between serum levels of
      homocysteine and fibrinogen with any metabolic syndrome criteria and related
      disorders except for a negative correlation of fibrinogen with high-density
      lipoprotein (HDL). CONCLUSION: In the present work, patients with lichen planus
      were found to have higher makers of both metabolic and cardiovascular risk
      factors in relation to controls most probably due to long standing inflammation.

PMID- 24330131
TI  - Streptomycete endophytes from anti-diabetic medicinal plants of the Western Ghats
      inhibit alpha-amylase and promote glucose uptake.
AB  - alpha-amylase inhibitor retards the liberation of glucose from dietary complex
      carbohydrates and delays the absorption of glucose. The purpose of the study was
      to isolate and select alpha-amylase inhibitor-producing endophytic actinomycetes
      from the leaves and stems of Leucas ciliata and Rauwolfia densiflora, two of the
      well-known medicinal plants used in the treatment for diabetes. Sterilized plant
      samples were inoculated on the actinomycete isolation agar medium containing 50
      ppm cycloheximide and incubated for 4-8 weeks at room temperature. The
      actinomycetes were isolated on agar medium and identified on the basis of 16S
      rRNA sequences, the isolates exhibiting >99% similarities were submitted to NCBI,
      and gene accession numbers were obtained. They were inoculated to International
      Streptomyces Project 1 medium (ISP 1) for fermentation. The extracts obtained
      were tested for the anti-diabetic potential by the inhibition of alpha-amylase by
      colorimetric assay and glucose uptake in the porcine hemidiaphragm. Streptomyces
      longisporoflavus (JX965948) isolated from the stem fragments of L. ciliata
      exhibited alpha-amylase inhibitory activity (IC50 values = 162.3 +/- 1.05 MUg ml
      1) in comparison with the standard AcarboseTM (IC50 value = 73.1 +/- 1.12 MUg ml
      1). Extract of Streptomyces sp. (JQ926174) from R. densiflora indicated glucose
      uptake in the porcine hemidiaphragm. Results indicate for the first time the
      potential of endophytic streptomycete extracts with anti-diabetic activity.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic actinomycetes were isolated from
      two medicinal species of the Western Ghats, a biodiversity 'hotspot' in southern
      India and screened for the anti-diabetic potential for inhibition of alpha
      amylase and improved glucose uptake in the porcine hemidiaphragm. Results
      indicate the inhibition of alpha-amylase by Streptomyces longisporoflavus extract
      with IC50 values of 162.3 +/- 1.05 MUg ml-1 in comparison with the standard
      inhibitor AcarboseTM with IC50 value 73.1 +/- 1.12 MUg ml-1. Further, extract
      from Streptomyces sp. showed increased glucose uptake by hemidiaphragm. The
      present investigation implicates the potential of endophytic actinomycetes as
      sources of anti-diabetic agents.

PMID- 24330132
TI  - Alterations in white matter microstructures and cognitive dysfunctions in benign
      childhood epilepsy with centrotemporal spikes.
AB  - BACKGROUND AND PURPOSE: Although benign childhood epilepsy with centrotemporal
      spikes (BECTS) is known to have good prognosis, patients often manifest
      neuropsychological impairments. This study aimed to investigate cognitive
      dysfunctions and their relationship with white matter microstructural changes in
      BECTS patients. METHODS: Nineteen BECTS and 25 normal subjects aged 7-16 years
      were included. Neuropsychological performances were assessed by the Wechsler
      Intelligence Scale for Children III, executive function tests, verbal and
      visuospatial memory tests, the verbal fluency and Boston naming tests. Diffusion
      tensor imaging (DTI) was performed to measure the fractional anisotropy (FA),
      axial (AD), radial (RD), and mean diffusivities (MD). The voxel-wise tract-based
      spatial statistics and region of interest methods were used for DTI, and their
      correlations with cognitive variables were analyzed. RESULTS: Patients with BECTS
      had lower intelligence quotient (IQ) scores compared with those of the control
      group. Higher AD and MD values were found in the left superior longitudinal
      fasciculus, the retrolenticular part of the internal capsule, posterior thalamic
      radiation, sagittal stratum and the body of the corpus callosum in BECTS patients
      compared with controls. Lower performances in verbal IQ, freedom from
      distractibility and processing speed were correlated with higher AD in the left
      superior fronto-occipital fasciculus, and lower verbal IQ scores were correlated
      with decreased FA values in the splenium of the corpus callosum in these
      patients. CONCLUSIONS: White matter microstructural changes predominantly in the
      left hemisphere might contribute to their cognitive abnormalities especially
      verbal IQ in BECTS patients.

PMID- 24330133
TI  - Choice of Fluids in Severe Septic Patients - A Cost-effectiveness Analysis
      Informed by Recent Clinical Trials.
AB  - Fluid resuscitation with colloids is an established second line therapy for
      septic patients. Evidence of relative efficacy outcomes is tempered by
      considerations of the relative costs of the individual fluids. An assessment of
      recent large clinical trials was performed, resulting in a ranking in the
      efficacy of these therapies. Probabilities for mortality and the need for renal
      replacement therapy (RRT) were derived and used to inform a decision analysis
      model comparing the effect of crystalloid, albumin and hydroxyethyl starch
      solutions in severe septic patients followed from hospital admission to 90 days
      in intensive care. The US payer perspective was used. Model inputs for costs and
      efficacy were derived from the peer-reviewed literature, assuming that that all
      fluid preparations are bio-equivalent within each class of these therapies.
      Probabilities for mortality and the need for renal replacement therapy (RRT) data
      were synthesized using a Bayesian meta-analysis. Relative to crystalloid therapy,
      0.21 life years were gained with albumin and 0.85 life years were lost with
      hydroxyethyl starch. One-way sensitivity analysis showed that the model's
      outcomes were sensitive to the cost of RRT but not to the costs of the actual
      fluids or any other costs. We conclude that albumin may be the most cost
      effective treatment in these patients when the total medical costs and iatrogenic
      morbidities involved in treating sepsis with fluids are considered. These results
      should assist and inform decision making in the choice of these drugs. 

PMID- 24330134
TI  - Thrombotic aortic restenosis after transapical SAPIEN valve implantation.
AB  - We describe a patient previously implanted with a SAPIEN Edwards valve by the
      transapical approach, who subsequently experienced a valve thrombosis. The
      literature on this subject is reviewed.

PMID- 24330135
TI  - Ultrasonographic appearance of histoplasmosis identified in the spleen in 15
      cats.
AB  - Histoplasmosis is the second most common fungal infection reported in the cat.
      The disseminated form involving lung, liver, lymph nodes, spleen, and bone marrow
      is a frequent manifestation of the disease. Limited information is available in
      the literature regarding the ultrasonographic appearance of the spleen in cats
      with disseminated or splenic histoplasmosis. A retrospective review of splenic
      ultrasound images from 15 cats confirmed to have histoplasmosis by splenic
      aspirates was performed. Size, echotexture, echogenicity, margin appearance,
      presence of nodules, and the overall shape of the spleen were reported in each
      case. Splenomegaly was documented in all cases (15/15) and a hypoechoic
      appearance of the spleen was documented in 14/15 of cases. The spleen was
      diffusely and uniformly affected in 14/15 (six homogenous and eight with a subtle
      mottled appearance) and had discrete nodules in 1/15 cats. Histoplasmosis should
      be included in the differential list for an enlarged and hypoechoic spleen in
      cats with consistent clinical findings. Additionally, ultrasound guided splenic
      aspirate may be a useful method to obtain a cytology sample for diagnosis.

PMID- 24330136
TI  - Guidelines for optimizing design and analysis of clinical studies of nutrient
      effects.
AB  - Presented here is a system to standardize clinical studies of nutrient effects,
      using nutrient-specific physiological criteria. These guidelines are based mainly
      on analysis of the typical sigmoid curve of biological response to nutrients and
      are intended for design, interpretation, and pooling of studies of nutrient
      effects. Five rules have been articulated for individual studies of nutrients,
      and six for systematic reviews and/or meta-analyses. 

PMID- 24330138
TI  - Draft Genomic DNA Sequence of the Facultatively Methylotrophic Bacterium
      Acidomonas methanolica type strain MB58.
AB  - Acidomonas methanolica (former name Acetobacter methanolicus) is a unique acetic
      acid bacterium capable to grow on methanol as a sole carbon source. Here we
      report the draft genome sequencing of A. methanolica type strain MB58, showing
      that it contains 3,270 protein-coding genes, including the genes involved in
      oxidation of methanol such as mxaFJGIRSACKL and hxlAB, and oxidation of ethanol
      such as adhAB and adhS. This article is protected by copyright. All rights
      reserved.

PMID- 24330137
TI  - Impact of enterococcal colonization and infection in solid organ transplantation
      recipients from the Swiss transplant cohort study.
AB  - BACKGROUND: The burden of enterococcal infections has increased over the last
      decades with vancomycin-resistant enterococci (VRE) being a major health problem.
      Solid organ transplantation is considered as a risk factor. However, little is
      known about the relevance of enterococci in solid organ transplantation
      recipients in areas with a low VRE prevalence. METHODS: We examined the
      epidemiology of enterococcal events in patients followed in the Swiss Transplant
      Cohort Study between May 2008 and September 2011 and analyzed risk factors for
      infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the
      1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%]
      infections, 205 [52.3%] colonizations, and 2 events with missing clinical
      information). Only 2 isolates were VRE. The highest infection rates were found
      early after liver transplantation (0.24/person-year) consisting in 58.6% of
      Enterococcus faecium. The highest colonization rates were documented in lung
      transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis
      with a betalactam antibiotic, and liver transplantation were significantly
      associated with infection. Previous antibiotic treatment, intensive care unit
      stay, and lung transplantation were associated with aminopenicillin resistance.
      Only 4/205 (2%) colonization events led to an infection. Adequate treatment did
      not affect microbiological clearance rates. Overall mortality was 8%; no deaths
      were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations
      and infections are frequent in transplant recipients. Progression from
      colonization to infection is rare. Therefore, antibiotic treatment should be used
      restrictively in colonization. No increased mortality because of enterococcal
      infection was noted.

PMID- 24330139
TI  - Auxiliary liver transplant is an ineffective treatment of primary hyperoxaluria.

PMID- 24330140
TI  - NEMATIC: a simple and versatile tool for the in silico analysis of plant-nematode
      interactions.
AB  - Novel approaches for the control of agriculturally damaging nematodes are sorely
      needed. Endoparasitic nematodes complete their life cycle within the root
      vascular cylinder, inducing specialized feeding cells: giant cells for root-knot
      nematodes and syncytia for cyst nematodes. Both nematodes hijack parts of the
      transduction cascades involved in developmental processes, or partially mimic the
      plant responses to other interactions with microorganisms, but molecular evidence
      of their differences and commonalities is still under investigation.
      Transcriptomics has been used to describe global expression profiles of their
      interaction with Arabidopsis, generating vast lists of differentially expressed
      genes. Although these results are available in public databases and publications,
      the information is scattered and difficult to handle. Here, we present a rapid,
      visual, user-friendly and easy to handle spreadsheet tool, called NEMATIC
      (NEMatode-Arabidopsis Transcriptomic Interaction Compendium;
      http://www.uclm.es/grupo/gbbmp/english/nematic.asp). It combines existing
      transcriptomic data for the interaction between Arabidopsis and plant
      endoparasitic nematodes with data from different transcriptomic analyses
      regarding hormone and cell cycle regulation, development, different plant
      tissues, cell types and various biotic stresses. NEMATIC facilitates efficient in
      silico studies on plant-nematode biology, allowing rapid cross-comparisons with
      complex datasets and obtaining customized gene selections through sequential
      comparative and filtering steps. It includes gene functional classification and
      links to utilities from several databases. This data-mining spreadsheet will be
      valuable for the understanding of the molecular bases subjacent to feeding site
      formation by comparison with other plant systems, and for the selection of genes
      as potential tools for biotechnological control of nematodes, as demonstrated in
      the experimentally confirmed examples provided. 

PMID- 24330141
TI  - The archaeology and genealogy of mentorship in English nursing.
AB  - In the United Kingdom, the concept of mentorship has been central to nurse
      education since the 1980s. Mentorship has become the definitive term used to
      denote the supervisory relationship of the student nurse with a qualified nurse
      who monitors and evaluates their skill development in the clinical area. The
      background against which the concept was established is examined through a
      consideration of the concepts of archaeology of knowledge and genealogy of
      knowledge as conceptualised by Michel Foucault. In particular, the Foucauldian
      concepts of power, discourses and the gaze are used to direct and shape the
      analysis. The paper explores the interplay of managerial dominance and
      professionalism and the ways in which mentorship can be used as a means of
      control and surveillance. 

PMID- 24330143
TI  - Relationship between endothelial dysfunction and kidney disease.

PMID- 24330142
TI  - Retrospective analysis of the natural history and management of serpiginous
      choroiditis in Australia and New Zealand.
AB  - BACKGROUND: To examine the prevalence of serpiginous choroidopathy in a
      predominantly Caucasian community, to examine associations between serpiginous
      choroiditis and other systemic diseases, and to report on the effect of
      immunosuppression on the long-term course of serpiginous choroiditis. DESIGN:
      Retrospective cohort study with patients from tertiary care centres and private
      practices. PARTICIPANTS: 18 patients, mean age 48 years at baseline. One patient
      was seen only once. Median follow-up was 69 months (5.8 years, range 0.4-29.7
      years). METHODS: Patients were identified using the Australian and New Zealand
      Ophthalmic Surveillance Unit. A chart analysis was performed for all patients.
      Three treatment groups were identified: no treatment, prednisolone monotherapy,
      or combination of prednisolone and immunosuppression. Negative binomial
      regression was used to calculate incidence rate ratios for patient relapse. MAIN
      OUTCOME MEASURES: Patient demographics, clinical features, associated systemic
      diseases, treatments administered and dates of relapse. RESULTS: The disease
      prevalence in Australia and New Zealand is 1 case per 1.5 million people. Five
      cases (28%) had a positive QuantiFERON. A total of 32 relapses were observed: 14
      while receiving no treatment, 11 on prednisolone and 7 on combination therapy.
      Compared with the no treatment group, the incidence rate ratio for prednisolone
      monotherapy and combination therapy was 1.29 and 2.92, respectively (95%
      confidence interval 0.40-4.14 and 0.96-8.88). CONCLUSION: Although the confidence
      intervals indicate that the difference in incidence rate ratios are not
      significant, these results suggest that there is a group of patients who have a
      benign course without long-term immunosuppression or corticosteroid treatment.

PMID- 24330144
TI  - The effect of timing of gamma-irradiation on hemolysis and potassium release in
      leukoreduced red cell concentrates stored in SAGM.
AB  - While irradiation of red cell concentrates (RCC) prevents graft-versus-host
      disease in susceptible transfusion recipients, it also damages red blood cells
      (RBC). To understand the ability of irradiation regulations to prevent
      transfusion of inferior units, we irradiated 980 RCC in saline-adenine-glucose
      mannitol (SAGM) using various combinations of pre-irradiation age and post
      irradiation storage times, and measured hemolysis and extracellular potassium
      levels. We observed unacceptably high hemolysis (>0.8%) in some RCC and elevated
      extracellular potassium levels in all gamma-irradiated RCC. This suggests that
      more restrictive storage times should be considered for RCC in SAGM. 

PMID- 24330145
TI  - Medial temporal lobe atrophy scores translated to clinical practice: editorial
      comment on 'influence of age, disease onset and ApoE4 on visual medial temporal
      lobe atrophy cut-offs'.

PMID- 24330146
TI  - Moisturizing treatment of patients with atopic dermatitis and ichthyosis vulgaris
      improves dry skin, but has a modest effect on gene expression regardless of FLG
      genotype.
AB  - BACKGROUND: Loss-of-function mutations in FLG (encoding filaggrin) are a
      predisposing factor for atopic dermatitis (AD) and cause ichthyosis vulgaris
      (IV). Patients with AD and IV display impaired skin barrier and dry skin, and
      altered epidermal expression of genes in pro-inflammatory and lipid metabolic
      pathways are often evident. OBJECTIVES: To evaluate the effect of three different
      moisturizers on skin barrier function and epidermal gene expression in patients
      with AD/IV in relation to FLG mutation status. METHODS: Patients (n = 43) were
      classified according to their FLG status: AD with FLG+/+ (n = 14), AD with FLG+/-
      (n = 14), and AD/IV with FLG-/- (n = 15). Dryness score and transepidermal water
      loss (TEWL) were monitored on volar forearms, and punch biopsies were taken for
      analysis of gene expression. Measurements were repeated after 4 weeks of
      treatment with either of two moisturizers on each forearm. RESULTS: Treatment
      with any of the three moisturizers significantly reduced dryness score and TEWL
      in the group as a whole. FLG-/- patients displayed the largest reduction in
      dryness score. Only minute changes occurred in the mRNA expression of 15 selected
      epidermal genes. CONCLUSIONS: Moisturizing treatment improves dry skin and
      certain aspects of abnormal skin barrier function, especially in patients with
      AD/IV and dual FLG mutations, but does not normalize the epidermal gene
      expression profile.

PMID- 24330147
TI  - IL-1beta-induced matrix metalloproteinase-3 regulates cell proliferation in rat
      dental pulp cells.
AB  - OBJECTIVE: We previously reported that matrix metalloproteinase-3(MMP-3)
      accelerates wound healing following dental pulp injury. In this study, we tested
      the hypothesis that induction of MMP-3 activity by interleukin-1beta would
      promote proliferation and apoptosis of dental pulp cells. MATERIALS AND METHODS:
      Dental pulp cells were isolated from rat incisors and subjected to interleukin
      1beta. Matrix metalloproteinase-3 mRNA and protein expression were assessed using
      reverse transcription-polymerase chain reaction and Western blotting,
      respectively. Matrix metalloproteinase-3 activity was measured using
      fluorescence. Dental pulp cell proliferation and apoptosis were determined using
      enzyme-linked immunosorbent assays (ELISA) for BrdU and DNA fragmentation,
      respectively. siRNA was used to reduce MMP-3 transcripts in these cells. RESULTS:
      Treatment with interleukin-1beta increased MMP-3 mRNA and protein levels as well
      as its activity in dental pulp cells. Cell proliferation was also markedly
      increased, with no changes in apoptosis observed. Treatment with siRNA against
      MMP-3 potently suppressed this interleukin-1beta-induced increase in MMP-3
      expression and activity, and also suppressed cell proliferation but unexpectedly
      increased apoptosis in these cells (P < 0.05). This siRNA-mediated increase in
      apoptosis could be reversed with exogenous MMP-3 stimulation (P < 0.05).
      CONCLUSIONS: Interleukin-1beta induces MMP-3-regulated cell proliferation and
      suppresses apoptosis in dental pulp cells.

PMID- 24330148
TI  - LMO2 (LIM domain only 2) is expressed in a subset of acute myeloid leukaemia and
      correlates with normal karyotype.
AB  - AIM: LMO2 is a transcription factor that plays a key role in haematopoiesis.
      Expression of LMO2 has been demonstrated in germinal centre B cells, various B
      cell lymphomas and T lymphoblastic lymphoma/leukaemia (T-ALL), but has not been
      studied extensively in acute myeloid leukaemia (AML). METHODS: We studied LMO2
      expression by immunohistochemistry in biopsies from a cohort of AML patients (n =
      196) and correlated it with established prognostic factors such as age, bone
      marrow morphology and cytogenetic findings. RESULTS: Forty per cent (79 of 196)
      of the samples from AML patients showed moderate/strong expression of LMO2
      protein. LMO2 expression showed a significant positive correlation with normal
      cytogenetics (65% versus 24%, P < 0.0001) and a moderately negative correlation
      with complex karyotype [rs (98) = -0.218, P < 0.002]. AML associated with core
      binding factor [(t(8;21)/inv(16)/t(16;16)] had low LMO2 expression compared to
      diploid karyotype (29% versus 65%; P = 0.013). Expression of LMO2 protein
      exhibited an insignificant association with age (P = 0.197). Lower expression of
      LMO2 protein was noted in AML associated with myelodysplasia-related changes,
      compared to AML subtypes based on FAB classification (M0-M7) (21% versus 44%, P =
      0.0187). CONCLUSIONS: LMO2 is expressed in a subset of AML patients and is
      associated with normal karyotype, which is different from T-ALL, where specific
      translocation (11p13) mediates protein expression.

PMID- 24330149
TI  - A novel, automated technology for multiplex biomarker imaging and application to
      breast cancer.
AB  - AIMS: Multiplexed immunofluorescence is a powerful tool for validating multigene
      assays and understanding the complex interplay of proteins implicated in breast
      cancer within a morphological context. We describe a novel technology for imaging
      an extended panel of biomarkers on a single, formalin-fixed paraffin-embedded
      breast sample and evaluating biomarker interaction at a single-cell level, and
      demonstrate proof-of-concept on a small set of breast tumours, including those
      which co-express hormone receptors with Her2/neu and Ki-67. METHODS AND RESULTS:
      Using a microfluidic flow cell, reagent exchange was automated and consisted of
      serial rounds of staining with dye-conjugated antibodies, imaging and chemical
      deactivation. A two-step antigen retrieval process was developed to satisfy all
      epitopes simultaneously, and key parameters were optimized. The imaging sequence
      was applied to seven breast tumours, and compared with conventional
      immunohistochemistry. Single-cell correlation analysis was performed with
      automated image processing. CONCLUSIONS: We have described a novel platform for
      evaluating biomarker co-localization. Expression in multiplexed images is
      consistent with conventional immunohistochemistry. Automation reduces
      inconsistencies in staining and positional shifts, while the fluorescent dye
      cycling approach dramatically expands the number of biomarkers which can be
      visualized and quantified on a single tissue section.

PMID- 24330150
TI  - A systematic analysis of commonly used antibodies in cancer diagnostics.
AB  - AIMS: Immunohistochemistry plays a pivotal role in cancer differential
      diagnostics. To identify the primary tumour from a metastasis specimen remains a
      significant challenge, despite the availability of an increasing number of
      antibodies. The aim of the present study was to provide evidence-based data on
      the diagnostic power of antibodies used frequently for clinical differential
      diagnostics. METHODS AND RESULTS: A tissue microarray cohort comprising 940
      tumour samples, of which 502 were metastatic lesions, representing tumours from
      18 different organs and four non-localized cancer types, was analysed using
      immunohistochemistry with 27 well-established antibodies used in clinical
      differential diagnostics. Few antibodies, e.g. prostate-specific antigen and
      thyroglobulin, showed a cancer type-related sensitivity and specificity of more
      than 95%. A majority of the antibodies showed a low degree of sensitivity and
      specificity for defined cancer types. Combinations of antibodies provided limited
      added value for differential diagnostics of cancer types. CONCLUSIONS: The
      results from analysing 27 diagnostic antibodies on consecutive sections of 940
      defined tumours provide a unique repository of data that can empower a more
      optimal use of clinical immunohistochemistry. Our results highlight the benefit
      of immunohistochemistry and the unmet need for novel markers to improve
      differential diagnostics of cancer.

PMID- 24330151
TI  - Histopathological evaluation of resected colorectal cancer liver metastases: what
      should be done?

PMID- 24330152
TI  - Hypomethylation of long interspersed nucleotide element-1 in peripheral
      mononuclear cells of juvenile systemic lupus erythematosus patients in China.
AB  - AIM: Methylation abnormalities in T lymphocytes have been reported to correlate
      with systemic lupus erythematosus (SLE). Previous studies identified
      hypomethylation in the promoter of several genes linked to SLE. Long interspersed
      nucleotide element-1 (LINE-1) constitutes 17-25% of the human genome, and LINE-1
      hypomethylation has been reported in SLE. Limited information is available
      regarding LINE-1 methylation in juvenile SLE (JSLE). METHOD: Methylation levels
      of LINE-1 in peripheral blood mononuclear cells (PBMCs) from 59 JSLE and 47
      control samples were examined by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry. Total homocysteine (tHcy) concentrations in plasma
      were measured by immunoassay. RESULTS: Significant hypomethylation of LINE-1 was
      observed in PBMCs from JSLE patients (60.93% in cases compared with 62.88% in
      controls, P = 0.001). Significant LINE-1 hypomethylation was observed in active
      SLE compared to controls (60.66% vs. 62.88%, P = 0.001). According to other
      clinical parameters, a significant correlation was found between LINE-1
      methylation levels and the Systemic Lupus Erythematosus Disease Activity Index
      2000 (SLEDAI-2000) of the cases (r = -0.285, P = 0.032). The risk of JSLE
      increased with decreasing levels of LINE-1 methylation, with an odds ratio of
      14.5 (95% CI: 2.8-75.6, P = 0.002). Cases had significantly higher plasma
      concentrations of tHcy than controls (15.11 vs. 11.02 MUmol/L, P = 0.028); the
      correlation between LINE-1 methylation levels and tHcy was significant (r = -0.4,
      P = 0.013). Correlations between methylation levels of LINE-1 and complement
      component 3 were significant (r = 0.317, P = 0.044; r = 0.387, P = 0.031, in
      total JSLE and active JSLE, respectively). CONCLUSION: Hypomethylation of LINE-1
      is associated with risk of JSLE, and LINE-1 methylation levels were related to
      disease activity and clinical manifestations. The correlation between tHcy levels
      and LINE-1 methylation was significant.

PMID- 24330153
TI  - Host genome variations and risk of infections during induction treatment for
      childhood acute lymphoblastic leukaemia.
AB  - OBJECTIVES: To investigate association of host genomic variation and risk of
      infections during treatment for childhood acute lymphoblastic leukaemia (ALL).
      METHODS: We explored association of 34,000 single-nucleotide polymorphisms (SNPs)
      related primarily to pharmacogenomics and immune function to risk of infections
      among 69 ALL patients on induction therapy. RESULTS: Forty-eight (70%) patients
      experienced infectious events including 23 with positive blood cultures.
      Infectious events and positive blood cultures were associated significantly with
      24 and 21 SNPs, respectively (P < 0.01). Classification and regression tree
      analysis demonstrated rs11033797 (OR51F1), rs2835265 (CBR1), rs28627172 (POLDIP3)
      and rs1129844 (CCL11) to be predictive of outcome. Among 61 patients for whom
      read-outs were available for all four SNPs, 40 of 41 patients with the worst SNP
      profile experienced at least one infectious event compared with five of the
      remaining 20 patients (Hazard ratio 9.0, 95% CI 3.4-23.5, which was unchanged
      after adjustments for neutrophil counts). Pathway analysis identified variations
      in 'G-protein-coupled receptor (GPCR) downstream signalling', 'Bile acid and bile
      salt metabolism' and 'Class I MHC-mediated antigen processing and presentation'
      to be highly predictive of infections. CONCLUSIONS: Our data indicate that host
      genomic profiling may predict the risk of infections during induction therapy.
      This may facilitate development of individualised supportive care.

PMID- 24330154
TI  - Causes and consequences of occupational stress in emergency nurses, a
      longitudinal study.
AB  - AIM: This longitudinal study examines the influence of changes over time in work
      and organisational characteristics on job satisfaction, work engagement,
      emotional exhaustion, turnover intention and psychosomatic distress in emergency
      room nurses. BACKGROUND: Organisational and job characteristics of nurses are
      important predictors of stress-health outcomes. Emergency room nurses are
      particularly exposed to stressful work-related events and unpredictable work
      conditions. METHOD: The study was carried out in 15 emergency departments of
      Belgian general hospitals in 2008 (T1) and 18 months later (T2) (n = 170).
      RESULTS: Turnover rates between T1 and T2 were high. Important changes over time
      were found in predictors and outcomes. Changes in job demand, control and social
      support predicted job satisfaction, work engagement and emotional exhaustion. In
      addition, changes in reward, social harassment and work agreements predicted work
      engagement, emotional exhaustion and intention to leave, respectively.
      CONCLUSIONS: Work-related interventions are important to improve occupational
      health in emergency room nurses and should focus on lowering job demands,
      increasing job control, improving social support and a well-balanced reward
      system. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should be aware of
      the causes and consequences of occupational stress in emergency room nurses in
      order to enable preventive interventions.

PMID- 24330155
TI  - Barriers and facilitators to attending pre-pregnancy care services: the ATLANTIC
      DIP experience.
AB  - AIMS: Pre-pregnancy care programmes can help to reduce morbidity and mortality
      associated with pregnancy in women with diabetes. However, uptake of a free pre
      pregnancy care programme along the Irish Atlantic seaboard was only 30%. This
      study sought to better understand why women with diabetes mellitus (Type 1 and
      Type 2) choose to attend pre-pregnancy care services and to identify perceived
      barriers to attendance. METHODS: A participative health research method called
      the participative research process was used to facilitate 14 women with diabetes
      mellitus to create 'webs of ideas' on the reasons for attendance and non
      attendance at a pre-pregnancy care programme, and potential solutions for each
      obstacle. RESULTS: The participants identified information on the risks of
      pregnancy as crucial for all childbearing women with diabetes, as lack of
      information was a major obstacle to attendance at pre-pregnancy care programmes.
      Practical constraints such as childcare difficulties and work commitments were
      also identified. Participants stressed that health practitioners need to focus on
      positive aspects of pregnancy and childbearing rather than focusing solely on the
      problematic aspects for women with diabetes mellitus. CONCLUSIONS: Women with
      diabetes need support and reassurance about their ability to control blood
      glucose and have a successful pregnancy while coping with the multiple challenges
      inherent in diabetes management and pregnancy. To increase uptake of pre
      pregnancy care, a norm needs to be established that situates pre-pregnancy care
      as something every woman with diabetes will do, whether or not she is actively
      contemplating becoming a mother at the time. Active use of social media and
      facilitating peer support should be encouraged in pre-pregnancy services to
      facilitate attendance. The time has come to incorporate the skills of a clinical
      psychologist in the delivery of a pre-pregnancy service.

PMID- 24330157
TI  - Cerebrospinal fluid alpha-synuclein levels in Parkinson's disease--changed or
      unchanged?

PMID- 24330156
TI  - Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with
      diabetes: a randomized double-blind placebo-controlled study.
AB  - BACKGROUND: In the present study, we examined the effect of a two-herb
      traditional Chinese medicine (NF3), comprised of Astragali Radix and Radix
      Rehmanniae, on the healing of diabetic foot ulcer and the possible molecular
      mechanisms involved. METHODS: This was a prospective randomized double-blind
      placebo-controlled study. Sixteen diabetic patients were randomized to receive
      either placebo or NF3 for 6 months. Ulcer healing and sensory changes were
      examined. Molecular studies included measurement of serum tumor necrosis factor
      (TNF)-alpha and RNA microarray investigation. RESULTS: The daily rate of
      reduction in ulcer area was 3.55% in the NF3 group and 1.52% in the placebo group
      (P = 0.062). In the index limb, the number of negative tests for sensory
      neuropathy using monofilament was reduced from 27% to 7% in the NF3 group and
      from 37% to 35% in the placebo group (P < 0.001). In addition, NF3 significantly
      decreased serum TNF-alpha levels (P = 0.034). Microarray studies revealed
      concerted changes following NF3 treatment in the expression of genes implicated
      in fibroblast regeneration, angiogenesis, and anti-inflammation. CONCLUSIONS: In
      this proof-of-concept study, 6-month treatment with NF3 was associated with
      improved wound healing and sensation accompanied by concerted changes in gene
      expression.

PMID- 24330158
TI  - Trafficking of the myrosinase-associated protein GLL23 requires
      NUC/MVP1/GOLD36/ERMO3 and the p24 protein CYB.
AB  - Proteins detrimental to endoplasmic reticulum (ER) morphology need to be
      efficiently exported. Here, we identify two mechanisms that control trafficking
      of Arabidopsis thalianaGLL23, a 43 kDa GDSL-like lipase implicated in
      glucosinolate metabolism through its association with the beta-glucosidase
      myrosinase. Using immunofluorescence, we identified two mutants that showed
      aberrant accumulation of GLL23: large perinuclear ER aggregates in the nuclear
      cage (nuc) mutant; and small compartments contiguous with the peripheral ER in
      the cytoplasmic bodies (cyb) mutant. Live imaging of fluorescently tagged GLL23
      confirmed its presence in the nuc and cyb compartments, but lack of fluorescent
      signals in the wild-type plants suggested that GLL23 is normally post
      translationally modified for ER export. NUC encodes the MVP1/GOLD36/ERMO3
      myrosinase-associated protein, previously shown to have vacuolar distribution.
      CYB is an ER and Golgi-localized p24 type I membrane protein component of coat
      protein complex (COP) vesicles, animal and yeast homologues of which are known to
      be involved in selective cargo sorting for ER-Golgi export. Without NUC, GLL23
      accumulates in the ER this situation suggests that NUC is in fact active in the
      ER. Without CYB, both GLL23 and NUC were found to accumulate in cyb compartments,
      consistent with a role for NUC in GLL23 processing and indicated that GLL23 is
      the likely sorting target of the CYB p24 protein.

PMID- 24330159
TI  - Long-term coevolution between avian brood parasites and their hosts.
AB  - Coevolutionary theory predicts that the most common long-term outcome of the
      relationships between brood parasites and their hosts should be coevolutionary
      cycles based on a dynamic change selecting the currently least-defended host
      species, given that when well-defended hosts are abandoned, hosts will be
      selected to decrease their defences as these are usually assumed to be costly.
      This is assumed to be the case also in brood parasite-host systems. Here I
      examine the frequency of the three potential long-term outcomes of brood parasite
      host coevolution (coevolutionary cycles, lack of rejection, and successful
      resistance) in 182 host species. The results of simple exploratory comparisons
      show that coevolutionary cycles are very scarce while the lack of rejection and
      successful resistance, which are considered evolutionary enigmas, are much more
      frequent. I discuss these results considering (i) the importance of different
      host defences at all stages of the breeding cycle, (ii) the role of phenotypic
      plasticity in long-term coevolution, and (iii) the evolutionary history of host
      selection. I suggest that in purely antagonistic coevolutionary interactions,
      such as those involving brood parasites and their hosts, that although cycles
      will exist during an intermediate phase of the interactions, the arms race will
      end with the extinction of the host or with the host acquiring successful
      resistance. As evolutionary time passes, this resistance will force brood
      parasites to use previously less suitable host species. Furthermore, I present a
      model that represents the long-term trajectories and outcomes of coevolutionary
      interactions between brood parasites and their hosts with respect to the
      evolution of egg-rejection defence. This model suggests that as an increasing
      number of species acquire successful resistance, other unparasitized host species
      become more profitable and their parasitism rate and the costs imposed by brood
      parasitism at the population level will increase, selecting for the evolution of
      host defences. This means that although acceptance is adaptive when the
      parasitism rate and the costs of parasitism are very low, this cannot be
      considered to represent an evolutionary equilibrium, as conventional theory has
      done to date, because it is not stable. 

PMID- 24330160
TI  - Ability of vitamin D to reduce inflammation in adults without acute illness.
AB  - In vitro studies and some clinical studies suggest that vitamin D plays an
      important role in reducing inflammation. The objective of this review was to
      examine recent evidence that vitamin D status influences the level of
      inflammation in adults without acute illness or injury. Five large cross
      sectional studies and two randomized controlled trials are the focus of this
      review. Associations between 25-hydroxyvitamin D (25OHD) and inflammation markers
      are significant and inverse in study populations with low 25OHD levels (<21
      ng/mL). They are also inverse in adults with relatively high inflammation levels.
      These associations in the few available randomized controlled vitamin D
      intervention trials have been null; this may be because they were not examined in
      populations with sufficiently low levels of 25OHD or high levels of inflammation.

PMID- 24330161
TI  - Risk factors associated with preoperative fecal carriage of extended-spectrum
      beta-lactamase-producing Enterobacteriaceae in liver transplant recipients.
AB  - OBJECTIVE: The aim of the study was to identify risk factors associated with pre
      transplant fecal carriage of extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae in liver transplant recipients. PATIENTS AND METHODS: Over a 3
      year period (January 2009-December 2011), 317 patients who underwent liver
      transplantation were screened preoperatively for fecal carriage of ESBL-producing
      Enterobacteriaceae. Risk factors for fecal carriage were investigated by
      univariate analysis and stepwise logistic regression. RESULTS: Of the 317
      patients screened, 50 (15.7%) harbored an ESBL-producing isolate. Previous
      infection with an ESBL-producing organism had developed during the last 6 months
      in 20% of fecal carriers versus in none of the non-carriers. Other variables
      associated with fecal carriage were a model for end-stage liver disease score
      >=25, pre-transplant stay in the intensive care unit >=48 h, hospital stay >=10
      days in the last 6 months, a history of spontaneous bacterial peritonitis (SBP),
      exposure to a beta-lactam agent in the last month, and prophylaxis with
      norfloxacin. Independent predictors of fecal carriage in the multivariate
      logistic regression model were exposure to a beta-lactam agent in the month
      preceding transplantation (odds ratio [OR] = 7.8, confidence interval [CI] = 4
      15.5, P < 0.001), and a history of SBP (OR = 2.4, CI = 1.1-4.9, P = 0.02).
      CONCLUSIONS: Previous infection with an ESBL-producing isolate, recent exposure
      to a beta-lactam agent, and a history of SBP are risk factors for preoperative
      fecal carriage of ESBL-producing Enterobacteriaceae in liver transplant
      recipients. Patients at risk of fecal carriage should receive intraoperative
      prophylaxis and, when necessary, empiric postoperative antimicrobial treatment
      that includes coverage for these organisms.

PMID- 24330162
TI  - Transcriptomic analysis of genes in the nitrogen recycling pathway of meat-type
      chickens divergently selected for feed efficiency.
AB  - The understanding of the dynamics of ammonia detoxification and excretion in
      uricotelic species is lagging behind ureotelic species. The relative expression
      of genes involved in nitrogen recycling and feed efficiency in chickens is
      unknown. The objective of this study was to investigate the transcriptomics
      differences in key genes in the nitrogen (N) metabolism and purine biosynthesis
      pathway in a chicken population divergently selected for low (LRFI) or high
      (HRFI) residual feed intake at days 35 and 42 using duodenum, liver, pectoralis
      major (P. major) and kidney. There was a significant positive correlation between
      RFI and fecal N. The purine salvage pathway was activated in the LRFI compared
      with HRFI at days 42. The birds in the LRFI population attained greater feed
      efficiency by having lower FI, increasing their protein retention and producing
      adequate glutamine to maintain growth compared with the HRFI line. To maintain
      growth, excess N is deaminated mostly to generate purine nucleotides. Generating
      purine nucleotides primarily from the purine biosynthesis pathway is
      energetically costly, and to preserve energy, they preferentially generate
      nucleotides from the purine salvage pathway. The LRFI birds need to generate
      sufficient nucleotides to maintain growth despite reduced FI that then results in
      reduced fecal N. 

PMID- 24330164
TI  - Radiographic and echocardiographic assessment of left atrial size in 100 cats
      with acute left-sided congestive heart failure.
AB  - The aims of this study were to evaluate left atrial size in cats with acute left
      sided congestive heart failure. We hypothesized that left atrial size as
      determined by thoracic radiography can be normal in cats with acute left-sided
      congestive heart failure. One hundred cats with acute left-sided congestive heart
      failure in which thoracic radiography and echocardiography were performed within
      12 h were identified. Left atrial size was evaluated using right lateral and
      ventrodorsal radiographs. Measurements were compared to two-dimensional
      echocardiographic variables of left atrial size and left ventricular size. On
      echocardiography, left atrial enlargement was observed in 96% cats (subjective
      assessment) whereas maximum left atrial dimension was increased (>15.7 mm) in 93%
      cats. On radiographs left atrial enlargement (subjective assessment) was found in
      48% (lateral view), 53% (ventrodorsal view), and 64% (any view) of cats whereas
      left atrial enlargement was absent in 36% of cats in both views. Agreement
      between both methods of left atrial size estimation was poor (Cohen's kappa
      0.17). Receiver operating characteristic curve analysis identified a maximum
      echocardiographic left atrial dimension of approximately 20 mm as the best
      compromise (Youden index) between sensitivity and specificity in the prediction
      of radiographic left atrial enlargement. Left atrial enlargement as assessed by
      thoracic radiography may be absent in a clinically relevant number of cats with
      congestive heart failure. Therefore, normal left atrial size on thoracic
      radiographs does not rule out presence of left-sided congestive heart failure in
      cats with clinical signs of respiratory distress. 

PMID- 24330163
TI  - Reduced quality and accelerated follicle loss with female reproductive aging -
      does decline in theca dehydroepiandrosterone (DHEA) underlie the problem?
AB  - Infertility, spontaneous abortion and conception of trisomic offspring increase
      exponentially with age in mammals but in women there is an apparent acceleration
      in the rate from about age 37. The problems mostly commonly occur when the
      ovarian pool of follicles is depleted to a critical level with age but are also
      found in low follicular reserve of other etiologies. Since recent clinical
      studies have indicated that dehydroepiandrosterone (DHEA) supplementation may
      reverse the problem of oocyte quality, this review of the literature was
      undertaken in an attempt to find an explanation of why this is effective? In
      affected ovaries, oxygenation of follicular fluid is low, ultrastructural
      disturbances especially of mitochondria, occur in granulosa cells and oocytes,
      and considerable disturbances of meiosis occur. There is, however, no evidence to
      date that primordial follicles are compromised. In females with normal fertility,
      pre-antral ovarian theca cells respond to stimulation by inhibin B to provide
      androgen-based support for the developing follicle. With depletion of follicle
      numbers, inhibin B is reduced with consequent reduction in theca DHEA. Theca
      cells are the sole ovarian site of synthesis of DHEA, which is both a precursor
      of androstenedione and an essential ligand for peroxisome proliferator-activated
      receptor alpha (PPARalpha), the key promoter of genes affecting fatty acid
      metabolism and fat transport and genes critical to mitochondrial function. As
      well as inducing a plethora of deleterious changes in follicular cytoplasmic
      structure and function, the omega 9 palmitate/oleate ratio is increased by
      lowered activity of PPARalpha. This provides conditions for increased ceramide
      synthesis and follicular loss through ceramide-induced apoptosis is accelerated.
      In humans critical theca DHEA synthesis occurs at about 70 days prior to
      ovulation thus effective supplementation needs to be undertaken about four months
      prior to intended conception; timing which is also suggested by successful
      interventions to date. In humans and primates that undergo adrenarche, the
      adrenal zona reticularis (ZR) is the major site of DHEA production, however this
      is also reduced with age. Concomitant loss in function of the ZR might account
      for the acceleration in the rate of aging seen in humans in the late thirties'
      age group.

PMID- 24330165
TI  - Resisting, reproducing, resigned? Low-income pregnant women's discursive
      constructions and experiences of health and weight gain.
AB  - In this article, we use qualitative methodology to explore how 15 low-income
      women of diverse sociocultural location construct and experience health and
      weight gain during pregnancy, as well as how they position themselves in relation
      to messages pertaining to weight gain, femininity and motherhood that they
      encounter in their lives. Discussing the findings through a feminist
      poststructuralist lens, we conclude that the participants are complex, fragmented
      subjects, interpellated by multiple and at times conflicting subject positions.
      While the discourse of maternal responsibility (i.e. managing personal behaviours
      for the baby's health) is very much in evidence in their narratives, embodied
      experiences of pregnancy, lived experiences of financial constraints and
      religious beliefs provided some with an alternative discourse and resistant
      subject position. Participants also had mixed emotions about weight gain; they
      recognized the need to gain weight in order to have a healthy pregnancy, but
      weight gain was also not welcome as participants reproduced the dominant
      discourse of obesity and the discourse of 'feminine' bodily norms. Based on our
      results, we advocate for change to recent clinical guidelines and social
      discourses around pregnancy and weight gain, as well as for policies that provide
      pregnant women with a range of health-promoting resources. 

PMID- 24330167
TI  - Influence of abiotic factors on the antimicrobial activity of chitosan.
AB  - In an effort to bypass the adverse secondary effects attributed to the
      traditional therapeutic approaches used to treat skin disorders (such as atopic
      dermatitis), alternative antimicrobials have recently been suggested. One such
      antimicrobial is chitosan, owing to the already proved biological properties
      associated with its use. However, the influence of abiotic factors on such
      activities warrants evaluation. This research effort assessed the antimicrobial
      activity of chitosan upon skin microorganisms (Staphylococcus aureus,
      Staphylococcus epidermidis and Escherichia coli) in vitro when subject to a
      combination of different abiotic factors such as pH, ionic strength, organic
      acids and free fatty acids. Free fatty acids, ionic strength and pH significantly
      affected chitosan's capability of reducing the viable numbers of S. aureus. This
      antimicrobial action was potentiated in the presence of palmitic acid and a lower
      ionic strength (0.2% NaCl), while a higher ionic strength (0.4% NaCl) favored
      chitosan's action upon the reduction of viable numbers of S. epidermidis and E.
      coli. Although further studies are needed, these preliminary results advocate
      that chitosan can in the future be potentially considered as an antimicrobial of
      choice when handling symptoms associated with atopic dermatitis. 

PMID- 24330166
TI  - Genetic factors may play a prominent role in the development of coronary heart
      disease dependent on important environmental factors.
AB  - OBJECTIVE: The aim of the study was to examine whether various lifestyle factors
      modify genetic influences on coronary heart disease (CHD). DESIGN: The effect of
      lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and
      body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in
      a twin study of gene-environment interaction. Using structure equation modelling,
      we estimated genetic variance of CHD dependent on lifestyle factors. SUBJECTS: In
      total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and
      registered in the Swedish Twin Registry were eligible for this study. During the
      40-year follow-up, 7264 incident CHD events were recorded. RESULTS: Smoking,
      sedentary lifestyle and above average BMI were significantly associated with
      increased CHD incidence. The heritability of CHD decreased with increasing age,
      as well as with increasing levels of BMI, in both men and women. CONCLUSIONS: The
      difference in the genetic component of CHD as a function of BMI suggests that
      genetic factors may play a more prominent role for disease development in the
      absence of important environmental factors. Increased knowledge of gene
      environment interactions will be important for a full understanding of the
      aetiology of CHD.

PMID- 24330168
TI  - Possible association between cutaneous angiosarcoma of the scalp and nuchal
      salmon patch.

PMID- 24330169
TI  - Combination chemotherapy of carboplatin and paclitaxel for metastatic melanoma.

PMID- 24330170
TI  - Case of interdigital pilonidal sinus in a dog groomer.

PMID- 24330171
TI  - Multiple unilocular epidermal cysts presenting as a single lesion on the toe web.

PMID- 24330172
TI  - Onychogryphosis by an elastic wire.

PMID- 24330173
TI  - Finger nail configuration is influenced by mechanical forces on finger pads.

PMID- 24330174
TI  - Peritoneal loose body: a case report and comparison with encapsulated fat
      necrosis.

PMID- 24330175
TI  - Amyloid deposition in disseminated superficial porokeratosis with inflammatory
      stages.

PMID- 24330176
TI  - Wickham's striae presented with whitish ring-form on annular lichen planus.

PMID- 24330177
TI  - Case of tuberculosis cutis miliaris with epithelioid cell granuloma.

PMID- 24330178
TI  - Hidden tuberculous lymphadenitis and miliary tuberculosis in an erythema
      induratum patient: usefulness of interferon-gamma release assays in the
      diagnosis.

PMID- 24330179
TI  - Acute respiratory distress syndrome due to varicella zoster virus pneumonitis in
      an immunocompromised patient with herpes zoster.

PMID- 24330180
TI  - Impact of genital involvement on the sexual lives of vitiligo patients.

PMID- 24330181
TI  - Case of pemphigoid involving skin and mucous membrane with immunoglobulin G
      autoantibodies targeted to BP180 and laminin-332.

PMID- 24330182
TI  - Dramatic effect of sunitinib with rapid but transient improvement for psoriasis
      in a patient with metastatic renal carcinoma.

PMID- 24330183
TI  - Acquired hemophilia eclipsed by psoriatic arthralgia.

PMID- 24330184
TI  - Hidradenitis suppurativa and multiple dermatofibromas in a patient with
      ulcerative colitis.

PMID- 24330185
TI  - Sweet's syndrome presenting as drastically spreading generalized erythema with
      subcorneal pustulosis in myelodysplastic syndrome.

PMID- 24330186
TI  - Inferring the mode of colonization of the rapid range expansion of a solitary bee
      from multilocus DNA sequence variation.
AB  - Rapid geographic range expansions can have dramatic effects on the distribution
      of genetic diversity, both within and among populations. Based on field records
      collected over the past two decades in Western Europe, we report on the rapid
      geographic range expansion in Colletes hederae, a solitary bee species. To
      characterize how this expansion shaped the distribution of genetic diversity
      within and among populations, we performed a genetic analysis based on the
      sequencing of three nuclear loci (RNAp, CAD and WgL). We then simulated the
      evolution of DNA sequences under a spatially explicit model of coalescence to
      compare different hypotheses regarding the mode of colonization associated with
      this rapid expansion and to identify those that are most consistent with the
      observed molecular data. Our genetic analyses indicate that the range expansion
      was not associated with an important reduction in genetic diversity, even in the
      most recently colonized area in the United Kingdom. Moreover, little genetic
      differentiation was observed among populations. Our comparative analysis of
      simulated data sets indicates that the observed genetic data are more consistent
      with a demographic scenario involving relatively high migration rates than with a
      scenario based on a high reproduction rate associated with few migrants. In the
      light of these results, we discuss the factors that might have contributed to the
      rapid geographic range expansion of this pollen-specialist solitary bee species
      across Western Europe. 

PMID- 24330187
TI  - Fludarabine-based reduced-intensity conditioning regimen for hematopoietic stem
      cell transplantation in primary hemophagocytic lymphohistiocytosis.
AB  - OBJECTIVE: Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening
      condition that clinically characterized by fever, hepatosplenomegaly, and
      cytopenia. Hematopoietic stem cell transplantation (HSCT) is the only curative
      treatment option for patients diagnosed with primary HLH. METHODS: In this
      prospective study, we analyzed the outcome of 10 pediatric patients with primary
      HLH who had received HSCT, using reduced-intensity conditioning (RIC) regimen
      from 2007 to 2012. The median age at transplantation was 22.6 months (range: 6
      60). All of the patients received the same RIC regimen based on the use of
      fludarabine in combination with melphalan and horse antithymocyte globulin (ATG).
      Cyclosporine and methylprednisolone were used as graft-vs.-host disease (GvHD)
      prophylaxis. RESULTS: Hematopoietic engraftment occurred in all patients. At the
      present time, 8 patients with a median follow-up of 39 months are still alive and
      all of them are disease free. Acute and chronic GvHD developed in 6 and 2
      patients, retrospectively. Two patients died of sepsis and chronic GvHD during
      the study. CONCLUSION: Because of pretransplant infections caused by underlying
      immunodeficiency in patients with primary HLH, the use of less toxic regimen with
      RIC seems to be highly effective in this regard. Recipients of RIC transplant,
      with either full or mixed chimerism, had a long-term survival rate with no
      manifestation of primary HLH symptoms.

PMID- 24330188
TI  - Gold salt hypersensitivity associated with gallbladder edema.

PMID- 24330189
TI  - Ca(OH)2 application modes: in vitro alkalinity and clinical effect on bacteria.
AB  - AIM: To compare five calcium hydroxide (CH) products, CH-gutta-percha Plus
      points((r)) (CHGP) and conventional CH paste, for their ability to maintain
      alkalinity and to assess the clinical antimicrobial effect of CHGP. METHODOLOGY:
      Calcium hydroxide products were tested in the presence of standardized dentine
      powder or by titrating them with 1 mol HCl, expressed in mL (+/-SD). In a
      clinical trial, 21 single-rooted teeth with primary apical periodontitis were
      medicated with CHGP or with conventional CH paste. Bacterial samples were taken
      before and after chemo-mechanical preparation, after dressing and after leaving
      canals empty but sealed. To compare groups, anova with Tukey's test was used in
      the laboratory study and Fisher's exact test in the clinical study. Significance
      level was set at 5%. RESULTS: Pure CH with water (8.5 +/- 0.1) and Calasept (9.3
      +/- 0.1) maintained the highest alkalinity, followed by the gel-like products DS
      CaOH gel (7.3 +/- 0.3) and Ultracal XS (6.8 +/- 0.2) and then Biokalkki (6.3 +/-
      0.3) and Calxyl blue (5.1 +/- 0.2). All CH paste products had higher values
      compared with CHGP (1.6 +/- 0.1) (P < 0.05). Saturated solutions of the products
      were all neutralized to pH 8.6 within 24 h by dentine powder addition.
      Clinically, culture-negative results were obtained in 5/10 canals in the CHGP
      group and 7/11 with conventional CH (P > 0.05). CONCLUSIONS: Aqueous CH mixtures
      kept high pH better than viscous gel products or CHGP. Dentine powder had equal
      buffering effect on each product tested. CHGP and traditional CH paste both had
      an antimicrobial effect in the clinical setting, but there was no significant
      difference between the groups.

PMID- 24330190
TI  - Concomitant changes in cross-sectional area and water content in skeletal muscle
      after resistance exercise.
AB  - This study investigated how one bout (1EX) and three bouts (3EX) of strenuous
      resistance exercise affected the cross-sectional area (CSA) and water content
      (WC) of the quadriceps muscle and patella tendon (PT), 4 h and 52 h after the
      last exercise bout. Ten healthy untrained male subjects performed 1EX with one
      leg and 3EX with the other leg. CSA and WC were measured with magnetic resonance
      imaging 10, 20 and 30 cm proximal to the tibia plateau (TP) for the muscle, and
      at the proximal, central and distal site for the PT prior to exercise, and 4 h
      and 52 h after the last exercise bout. Ten centimeter above the TP, muscle CSA
      was significantly increased at 4 h (1EX: 13 +/- 5%; 3EX: 13 +/- 4%) and 52 h
      (1EX: 16 +/- 5%; 3EX: 16 +/- 5%) compared with baseline. Muscle WC was
      significantly increased at 4 h (1EX: 7 +/- 1%; 3EX: 6 +/- 2%) and 52 h (1EX: 8 +/
      2%; 3EX: 8 +/- 3%) compared to baseline. PT central CSA was significantly
      reduced at 52 h (3EX: 14 +/- 2%) compared with baseline and (3EX: 13 +/- 1%)
      compared with 4 h. Present data demonstrate that strenuous resistance exercise
      results in an acute increase in muscle WC and underlines the importance of
      ensuring sufficient time between the last exercise bout and the determination of
      anatomical dimensions in muscles.

PMID- 24330191
TI  - The DROOPING LEAF and OsETTIN2 genes promote awn development in rice.
AB  - The awn is a long needle-like appendage that, in some grass species, is formed on
      the lemma that encloses floral organs together with the palea. In rice, most wild
      species and most strains of Oryza sativa ssp. indica generate an awn, whereas
      most strains of O. sativa ssp. japonica do not. In japonica, the long-awn
      characteristic appears to have been lost during domestication and breeding
      programs. Here, we found that the genes DROOPING LEAF (DL) and OsETTIN2 (OsETT2)
      are involved in awn development in the awned indica strain Kasalath. Genetic
      analyses and RNA-silencing experiments indicate that DL and OsETT2 act
      independently in awn formation, and that either gene alone is not sufficient for
      awn development. Scanning electron microscopy revealed that the top region of the
      lemma (a putative awn primordium) is larger in an awned floret than in an awnless
      floret. OsETT2 is expressed in the awn primordium in the awned indica floret, but
      not in the awnless japonica floret except in the provascular bundle. DL is
      expressed underneath the primordium at similar levels in both indica and japonica
      florets, suggesting non-cell-autonomous action. We hypothesize that loss of
      expression of OsETT2 in the awn primordium is probably associated with the
      failure of awn formation in japonica strains.

PMID- 24330192
TI  - Evaluation of in vitro storage properties of apheresis platelets suspended in a
      bicarbonate-containing additive solution with low levels of plasma and stored
      with a 24-hour interruption of agitation.
AB  - BACKGROUND AND OBJECTIVES: PLT additive solutions (PAS) are useful for reducing
      the frequency and/or severity of plasma-associated transfusion reactions. A new
      PAS solution, PAS-5, containing 5% plasma, maintains in vitro PLT properties
      during 7-day storage. Periods with interruption of agitation (IA) <=24 h
      routinely occur during PLT shipment and do not usually compromise platelet
      quality. The aim of the study was to evaluate the properties of PLTs stored for 7
      days in 95% PAS-5/5% plasma subjected to a 24-h IA. MATERIALS AND METHODS: Double
      apheresis Amicus units (n = 12) were collected using a manual PAS-5 addition to
      hyperconcentrated PLTs. PLT units were equally divided in two containers. Control
      and test PLTs were stored with continuous agitation at 20-24 degrees C except for
      24-h IA period for test units between days 2-3. RESULTS: During storage, levels
      of glucose, lactate, mitochondrial membrane potential and aggregation
      significantly differed in test units compared to those of control. The pH levels
      of test PLTs were less than those of control units with 7/12 test units having
      pHs <6.2 on Day 7 compared to 1/12 control units. Morphology score, GP1balpha
      expression, ESC values, superoxide production were also less, and activation was
      greater in test PLTs than those of control. All other parameters were similar
      between test and control units. CONCLUSION: PLTs stored in PAS-5 solution
      containing 5% plasma with a 24-h IA results in marked decrements in many in vitro
      PLT quality parameters during 7-day storage.

PMID- 24330193
TI  - Genomic resources notes accepted 1 June 2013-31 July 2013.
AB  - This article documents the public availability of (i) raw transcriptome sequence
      data, assembled contigs and UniProt BLAST hits from common crossbill (Loxia
      curvirostra) and Plasmodium relictum (lineage SGS1) obtained from a controlled
      infection experiment; and (ii) raw transcriptome sequence data and 66 596 SNPs
      for the white-tailed deer (Odocoileus virginianus). 

PMID- 24330195
TI  - Which family physicians work routinely with nurse practitioners, physician
      assistants or certified nurse midwives.
AB  - PURPOSE: Facing rising numbers of insured with implementation of the Affordable
      Care Act, policy makers are interested in building teams of providers that can
      accommodate a growing demand for primary care services. Nurse Practitioners
      (NPs), Physician Assistants (PAs), and Certified Nurse Midwives (CNMs) already
      augment the physician workforce, particularly in rural areas. Our objective was
      to determine what physician and areal-level characteristics were associated with
      working with NPs, PAs or CNMs. METHODS: The sample consisted of a convenience
      sample of physicians through the American Board of Family Medicine (ABFM) website
      in the fall of 2011. We linked these data to demographic and practice information
      collected by the ABFM and with provider information supplied from the National
      Provider Identifier file aggregated at the Primary Care Service Area level.
      Hierarchical logistic regression models were used to determine variables
      associated with working with NPs, PAs, or CNMs. FINDINGS: Of the 3,855 family
      physicians in our sample, 60% reported routinely working with NPs, PAs, or CNMs.
      In regression analysis, characteristics positively associated with working with
      NPs, PAs, or CNMs were providing gynecological care (Odds Ratio = 1.23 [95%
      confidence interval, 1.06-1.42]), multispecialty group practice (OR = 1.72 [1.36
      2.18]), any rural setting, and higher availability of PAs (OR = 1.40 [1.10
      1.79]). Restrictive NP scope of practice laws failed to reach significance (OR =
      0.86 [0.71-1.05]). CONCLUSIONS: This study suggests that the number of family
      physicians routinely working with NPs, PAs, and CNMs continues to increase, which
      may allow for improved access to health care, particularly in rural areas.

PMID- 24330194
TI  - Emotional graphic cigarette warning labels reduce the electrophysiological brain
      response to smoking cues.
AB  - There is an ongoing public debate about the new graphic warning labels (GWLs)
      that the Food and Drug Administration (FDA) proposes to place on cigarette packs.
      Tobacco companies argued that the strongly emotional images FDA proposed to
      include in the GWLs encroached on their constitutional rights. The court ruled
      that FDA did not provide sufficient scientific evidence of compelling public
      interest in such encroachment. This study's objectives were to examine the
      effects of the GWLs on the electrophysiological and behavioral correlates of
      smoking addiction and to determine whether labels rated higher on the emotional
      reaction (ER) scale are associated with greater effects. We studied 25 non
      treatment-seeking smokers. Event-related potentials (ERPs) were recorded while
      participants viewed a random sequence of paired images, in which visual smoking
      (Cues) or non-smoking (non-Cues) images were preceded by GWLs or neutral images.
      Participants reported their cigarette craving after viewing each pair. Dependent
      variables were magnitude of P300 ERPs and self-reported cigarette craving in
      response to Cues. We found that subjective craving response to Cues was
      significantly reduced by preceding GWLs, whereas the P300 amplitude response to
      Cues was reduced only by preceding GWLs rated high on the ER scale. In
      conclusion, our study provides experimental neuroscience evidence that weighs in
      on the ongoing public and legal debate about how to balance the constitutional
      and public health aspects of the FDA-proposed GWLs. The high toll of smoking
      related illness and death adds urgency to the debate and prompts consideration of
      our findings while longitudinal studies of GWLs are underway. 

PMID- 24330196
TI  - Adult-onset eccrine angiomatous hamartoma: report of a rare entity with unusual
      histological features.

PMID- 24330197
TI  - Masked hypertension as an unrecognized destructive condition.

PMID- 24330198
TI  - Severe life-threatening Ehrlichia chaffeensis infections transmitted through
      solid organ transplantation.
AB  - BACKGROUND: Donor-derived infections from organ transplantation are rare
      occurrences with preoperative screening practices. Ehrlichia chaffeensis, a tick
      borne illness, transmitted through solid organ transplantation has not been
      reported previously to our knowledge. We present cases of 2 renal allograft
      recipients who developed severe E. chaffeensis infection after receipt of organs
      from a common deceased donor. METHODS: The 2 renal transplant patients who
      developed E. chaffeensis infection are reported in case study format with review
      of the literature. RESULTS: Approximately 3 weeks after renal transplantation,
      both patients developed an acute febrile illness and rapid clinical decline.
      Recipient A underwent an extensive infectious workup that revealed positive E.
      chaffeensis DNA from polymerase chain reaction on peripheral blood. Recipient B's
      clinical team obtained acute and convalescent antibody titers for E. chaffeensis,
      which demonstrated acute infection. Recipients A and B were treated with
      doxycycline and tigecycline, respectively, with clinical cure. CONCLUSIONS: These
      cases demonstrate that tick-borne pathogens, such as E. chaffeensis, can be
      transmitted through renal transplantation. E. chaffeensis can be associated with
      excessive morbidity and mortality, commonly owing to delay in diagnosis and poor
      response to non-tetracycline antibiotics. In populations with endemic tick-borne
      illness, donors should be questioned about tick exposure, and appropriate
      antibiotics can be administered if indicated.

PMID- 24330200
TI  - Pediatric lung allocation: the rest of the story.

PMID- 24330199
TI  - Signalling C-type lectin receptors, microbial recognition and immunity.
AB  - Signalling C-type lectin receptors (CLRs) are crucial in shaping the immune
      response to fungal pathogens, but comparably little is known about the role of
      these receptors in bacterial, viral and parasitic infections. CLRs have many
      diverse functions depending on the signalling motifs in their cytoplasmic
      domains, and can induce endocytic, phagocytic, antimicrobial, pro-inflammatory or
      anti-inflammatory responses which are either protective or not during an
      infection. Understanding the role of CLRs in shaping anti-microbial immunity
      offers great potential for the future development of therapeutics for disease
      intervention. In this review we will focus on the recognition of bacterial, viral
      and parasitic pathogens by CLRs, and how these receptors influence the outcome of
      infection. We will also provide a brief update on the role of CLRs in antifungal
      immunity. 

PMID- 24330201
TI  - Clinical presentation of pediatric multiple sclerosis before puberty.
AB  - BACKGROUND AND PURPOSE: Multiple sclerosis (MS) onset before puberty is extremely
      rare and establishment of diagnosis is often difficult due to atypical
      presentation. The study aims to identify the typical presentation of MS in this
      age group. METHODS: Pediatric MS patients were identified from the database of
      the Center for Multiple Sclerosis in Childhood and Adolescence at the University
      Medical Center Gottingen, Germany. Inclusion criteria were a relapsing-remitting
      initial disease course and minimum disease duration of 4 years. RESULTS: Forty
      seven pre-pubertal (<11 years) and 41 post-pubertal (14-16 years) MS patients
      were compared. Before puberty an even gender ratio was found. The pre-pubertal
      patients were more likely to have a polysymptomatic severe first attack with
      motor and brainstem involvement, sphincter dysfunction, cognitive disturbances
      and milder residual neurological sequelae after the first episode whilst the post
      pubertal patients predominantly presented with optic neuritis and sensory
      symptoms. The initial symptom pattern prevailed over the first 2 years of
      disease. Presentation of pre-pubertal boys and girls did not differ
      significantly. CONCLUSIONS: To facilitate early diagnosis it is important to
      recognize that pre-pubertal MS presents with a specific pattern of symptoms that
      is maintained over the first two disease years.

PMID- 24330202
TI  - Orbital immunoglobulin-G4-related disease: case series and literature review.
AB  - Immunoglobulin-G4-related disease (IgG4-RD) is a distinct group of diseases
      characterized by elevated serum IgG4 titres and infiltration of affected organs
      by IgG4-positive plasma cells. IgG4-RD can involve any ocular adnexal tissue.
      They have a distinct prognosis and pattern of tissue involvement and hence need
      to be differentiated from orbital lesions with similar clinicopathological
      features. We report three cases of IgG4-RD and review the literature extensively
      discussing various aspects of this novel entity. 

PMID- 24330203
TI  - Accumulation of periplasmic enterobactin impairs the growth and morphology of
      Escherichia coli tolC mutants.
AB  - TolC is the outer membrane component of tripartite efflux pumps, which expel
      proteins, toxins and antimicrobial agents from Gram-negative bacteria.
      Escherichia coli tolC mutants grow well and are slightly elongated in rich media
      but grow less well than wild-type cells in minimal media. These phenotypes have
      no physiological explanation as yet. Here, we find that tolC mutants have highly
      aberrant shapes when grown in M9-glucose medium but that adding iron restores
      wild-type morphology. When starved for iron, E. coli tolC mutants synthesize but
      cannot secrete the siderophore enterobactin, which collects in the periplasm.
      tolC mutants unable to synthesize enterobactin display no growth or morphological
      defects, and adding exogenous enterobactin recreates these aberrations,
      implicating this compound as the causative agent. Cells unable to import
      enterobactin across the outer membrane grow normally, whereas cells that import
      enterobactin only to the periplasm become morphologically aberrant. Thus, tolC
      mutants grown in low iron conditions accumulate periplasmic enterobactin, which
      impairs bacterial morphology, possibly by sequestering iron and inhibiting an
      iron-dependent reaction involved in cell division or peptidoglycan synthesis. The
      results also highlight the need to supply sufficient iron when studying TolC
      directed export or efflux, to eliminate extraneous physiological effects. 

PMID- 24330204
TI  - Transcatheter patent foramen ovale closure versus medical therapy for cryptogenic
      stroke: a meta-analysis of randomized clinical trials.
AB  - BACKGROUND: There is an association between cryptogenic stroke and patent foramen
      ovale (PFO). The optimal treatment strategy for secondary prevention remains
      unclear. The purpose of this study was to analyze aggregate data examining the
      safety and efficacy of transcatheter device closure versus standard medical
      therapy in patients with PFO and cryptogenic stroke. METHODS: A search of
      published data identified 3 randomized clinical trials for inclusion. The primary
      outcome was a composite end-point of death, stroke and transient-ischemic attack
      (TIA). Pre-defined subgroup analysis was performed with respect to baseline
      characteristics including age, sex, atrial septal aneurysm and shunt size. Data
      was synthesized using a random effects model and results presented as hazard
      ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A cohort of 2,303
      patients with a history of cryptogenic stroke and PFO were randomized to device
      closure (n = 1150) and medical therapy (n = 1153). Mean follow-up was 2.5 years.
      Transcatheter closure was not superior to medical therapy in the secondary
      prevention of stroke or TIA in intention-to-treat analysis (HR: 0.66, 95% CI:
      0.43 to 1.01; p = 0.056). However, the results were statistically significant
      using per-protocol analysis (HR: 0.64, 95% CI: 0.41 to 0.98; p = 0.043). Males
      had significant benefit with device closure (HR: 0.48, 95% CI: 0.24 to 0.96; p =
      0.038). CONCLUSIONS: In this meta-analysis, using intention-to-treat analysis,
      transcatheter device closure of PFO was not superior to standard medical therapy
      in the secondary prevention of cryptogenic stroke. Transcatheter closure was
      superior using per-protocol analysis.

PMID- 24330205
TI  - Quality of life in chronic haemodialysis and peritoneal dialysis patients in
      Turkey and related factors.
AB  - Turkey is the fifth country in Europe with regard to the number of patients
      receiving haemodialysis (HD). However, only a limited number of studies have
      comparatively investigated the factors that affect quality of life in
      haemodialysis and peritoneal dialysis (PD) patients in Turkey. The purpose of the
      study was to investigate the factors that affect quality of life in haemodialysis
      and peritoneal dialysis patients, as well as providing a comparison of quality of
      life between these groups. In this cross-sectional study, Quality of Life Scale
      and a data form was completed by 300 dialysis patients who received treatment at
      five hospital-based dialysis units in Istanbul, Turkey. The data were evaluated
      using arithmetic mean values, standard deviations, minimums, maximums,
      percentages, independent groups t-tests, Spearman correlation analyses and one
      way variance analyses. The quality of life values in peritoneal dialysis patients
      were found to be higher than those of haemodialysis patients (P < 0.05). It was
      concluded that the quality of life in chronic dialysis patients was affected by
      various factors. 

PMID- 24330206
TI  - Prognostic factors for risk stratification of adult cancer patients with
      chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.
AB  - Chemotherapy-induced febrile neutropenia patients are heterogeneous in their risk
      of adverse outcomes. Management strategies are tailored according to level of
      risk. Many emerging predictors for risk stratification remain controversial being
      based on single studies only. A systematic review was conducted to determine the
      strength of association of all identified predictors. Studies were obtained from
      electronic databases, grey literatures and reference lists. Methodological
      quality of studies was assessed for internal validity and representativeness.
      Seven studies (four prospective and three retrospective cohorts) investigating 22
      factors were reported. Fixed effects meta-analysis showed: hypotension and
      thrombocytopenia were significant predictors for high-risk. Additional predictors
      that might enhance performance of current models include: tachypnoea, presence of
      central venous catheter, duration and severity of neutropenia. Further research
      to investigate new factors/markers is needed to develop a robust prognostic
      model, which is the key to enhance patient safety. 

PMID- 24330207
TI  - Medication adherence feedback intervention predicts improved human
      immunodeficiency virus clinical markers.
AB  - Thirty-three participants in a human immunodeficiency virus (HIV) medication
      adherence feedback (MAF) intervention were compared with 58 HIV-positive non
      participants in laboratory-tested CD4 and viral load. The intervention provided
      adherence feedback and counselling based on a visual display from an electronic
      pill bottle (MEMS(TM) ). Multiple regression controlling for baseline CD4 and
      showed that postintervention CD4 was higher for MAF participants than for non-MAF
      participants. Non-MAF participants' CD4 significantly declined over time. MAF
      participants were also less likely than non-MAF participants to have a detectable
      postintervention viral load. 

PMID- 24330208
TI  - Patients' satisfaction with the quality of nursing care provided: the Saudi
      experience.
AB  - Patient's satisfaction has emerged as a central focus of health-care delivery
      during the last decades, and nursing care became one significant component of
      patient's satisfaction. The purpose of this study is to examine patients'
      satisfaction with quality of nursing care provided in Saudi Arabia. Cross
      sectional descriptive correctional design was used to recruit 100 patients from
      one regional hospital in Saudi Arabia. Data collected using structured interview
      from patients related to six dimensions of nursing care. Patients had a high
      level of satisfaction with nursing care provided (86% agreement rate). Language
      (56% disagreement rate), discharge information (56% disagreement rate) and
      availability (20% disagreement rate) have been identified with the lowest rates
      of patients satisfaction. Nursing leaders and health-care administrators need to
      maintain quality nursing care and develop strategies for improving nursing care
      emphasizing language as barrier and strategies of information dissemination. 

PMID- 24330209
TI  - Factors influencing quality of chest compression depth in nursing students.
AB  - The purpose of the study was to identify factors influencing quality of chest
      compression depth in nursing students. A convenience sample of 102 female nursing
      students enrolled in a cardiopulmonary resuscitation skills training session.
      Each student performed 3 min of chest compression skills on a Resusci Anne
      SkillReporter manikin for measurements of both depth and rate. Nursing students
      with correct compression depth (50-60 mm) had higher body weight (t = -2.02, P =
      0.046) and body mass index (t = -2.19, P = 0.031) compared with students in the
      incorrect depth group. Mean chest compression depth was shallower in underweight
      nursing students compared with normal weight or overweight students (F = 8.89, P
      < 0.001). Body weight was a significant factor influencing quality of chest
      compression depth (F = 4.25, P = 0.003). Educational intervention targeting
      underweight nursing students might need to enhance the quality of chest
      compression skills. 

PMID- 24330210
TI  - Developing evidence-based practice champions in the Maldives.
AB  - Evidence-based practice (EBP) is an approach that has gained recognition for
      facilitating the transfer of evidence into clinical practice. EBP champions is a
      strategy that can be adopted to encourage the uptake of EBP. This paper describes
      an action research project that was undertaken in Maldives. EBP champion model
      has been introduced in the Maldives early 2012 and aims to produce clinical
      leaders from variety of backgrounds who could implement EBP. This paper provides
      an extended discussion of the process that was undertaken to prepare EBP
      champions and their roles in implementing EBP. 

PMID- 24330211
TI  - Knowledge and attitudes of emergency nurses towards Crimean-Congo haemorrhagic
      fever in endemic regions of Turkey.
AB  - This study was carried out in order to determine knowledge and attitudes of
      emergency nurses about Crimean-Congo haemorrhagic Fever. This descriptive
      research was carried out where the disease is frequent, in six cities in Turkey.
      One hundred forty-three nurses who worked in the emergency room were recruited to
      the study. Data were collected with a questionnaire form and were analysed by chi
      squared test. The mean age of the nurses was 31.0 +/- 5.7 years. It was
      determined that 68.8% of the nurses claimed to have sufficient knowledge about
      the disease, 99.3% said that it was a virus that caused the disease, and 94.3%
      said that health-care personnel exposed to it were under great risk. It was
      concluded that most of the nurses had relatively good knowledge about the disease
      and that they did not want to run the high risk of infection and mortality by
      treating patients who had the disease. 

PMID- 24330212
TI  - Patient safety culture in acute care: a web-based survey of nurse managers' and
      registered nurses' views in four Finnish hospitals.
AB  - Nurse managers (NMs) and registered nurses (RNs) have key roles in developing the
      patient safety culture, as the nursing staff is the largest professional group in
      health-care services. We explored their views on the patient safety culture in
      four acute care hospitals in Finland. The data were collected from NMs (n = 109)
      and RNs (n = 723) by means of a Hospital Survey on Patient Safety Culture
      instrument and analyzed statistically. Both groups recognized patient safety
      problems and critically evaluated error-prevention mechanisms in the hospitals.
      RNs, in particular, estimated the situation more critically. There is a need to
      develop the patient safety culture of hospitals by discussing openly about them
      and learning from mistakes and by developing practices and mechanisms to prevent
      them. NMs have central roles in developing the safety culture at the system level
      in hospitals in order to ensure that nurses caring for patients do it safely. 

PMID- 24330213
TI  - Orthopaedic inpatient rehabilitation conducted by nursing staff in acute
      orthopaedic wards in Taiwan.
AB  - The purpose of this study was to understand the postoperative rehabilitation
      patterns of orthopaedic patients and to explore factors which affected the
      patients' functional recovery. A descriptive study with convenience sampling was
      performed. Study participants included orthopaedic inpatients from two hospitals
      in Taipei. In total, 100 patients were selected with an average age of 60.88 +/-
      17.61 years, of which the most common type of surgery was a total knee
      replacement (49.0%). Among these participants, 79.0% received rehabilitation
      guided by nursing staff, while only 6.0% were instructed by a physical therapist.
      The predictive factor for the time to first ambulation was the intensity of pain
      experienced on the second day after the operation, which accounted for 4.5% of
      the total variance. As for the functional status prior to discharge, predictive
      factors included the time to first ambulation and whether nursing staff provided
      instructions on rehabilitation, which accounted for 11.2% of the total variance.
      We recommend that professional staff should promote patient guidance toward
      postoperative rehabilitation, assistance in achieving the first ambulation and a
      resolution of obstacles to rehabilitation. 

PMID- 24330214
TI  - Barriers and facilitators to diabetes self-management: perspectives of older
      community dwellers and health professionals in China.
AB  - Little is known about self-management among people with Type 2 diabetes living in
      mainland China. Understanding the experiences of this target population is needed
      to provide socioculturally relevant education to effectively promote self
      management. The aim of this study was to explore perceived barriers and
      facilitators to diabetes self-management for both older community dwellers and
      health professionals in China. Four focus groups, two for older people with
      diabetes and two for health professionals, were conducted. All participants were
      purposively sampled from two communities in Shanghai, China. Six barriers were
      identified: overdependence on but dislike of western medicine, family role
      expectations, cuisine culture, lack of trustworthy information sources, deficits
      in communication between clients and health professionals, and restriction of
      reimbursement regulations. Facilitators included family and peer support, good
      relationships with health professionals, simple and practical instruction and a
      favourable community environment. The findings provide valuable information for
      diabetes self-management intervention development in China, and have implications
      for programmes tailored to populations in similar sociocultural circumstances. 

PMID- 24330215
TI  - The effect of non-pharmacological staged interventions on fatigue and dyspnoea in
      patients with chronic obstructive pulmonary disease: a randomized controlled
      trial.
AB  - The aim of this study was to examine the effect of non-pharmacological staged
      interventions on fatigue and dyspnoea in patients with chronic obstructive
      pulmonary disease. A randomized controlled trial was conducted with 64 patients
      in a tertiary hospital in China from 2010 to 2011. Patients were randomly
      assigned to the control group (n = 32), who received routine care, and the
      intervention group (n = 32), who received additional non-pharmacological staged
      interventions. The Multidimensional Fatigue Inventory and the five-grade Medical
      Research Council dyspnoea scale were used to collect data at baseline and after 6
      weeks. Compared with the control group, patients in the intervention group had
      significantly lower scores on general fatigue (P < 0.001), physical fatigue (P <
      0.001), reduced activity (P < 0.001) and reduced motivation (P = 0.03) and had
      better relief of dyspnoea (P = 0.02). Our study showed that non-pharmacological
      staged interventions were effective in relieving fatigue and dyspnoea in patients
      with chronic obstructive pulmonary disease. 

PMID- 24330216
TI  - Validation of the Portuguese version of the Stanford presenteeism scale in
      nurses.
AB  - The SPS-6 is a tool that is widely used to test the characteristic of
      presenteeism, which is the ability to concentrate and work despite health
      problems. This concept refers to the phenomenon of people-despite complaining and
      being ill--going to work instead of resting and taking sick leave. The aim of
      this study was to assess the validity and reliability of the SPS-6. Internal
      consistency was examined by Cronbach's alpha. The Perceived Stress Scale was
      selected to determine the external validity of the SPS-6. Exploratory and
      confirmatory factor analyses were used to evaluate construct validity. The
      reliability analysis of all 126 registered nurses entered in the study showed
      satisfactory results (Cronbach's alpha = 0.83). External validity was evidenced
      by the significant negative correlation between the SPS-6 and the perceived
      stress scores. The factor analysis resulted in a two-component solution that
      conjointly accounted for 52.4% of the variance. A confirmatory factor analysis
      showed an adequate model fit. The Portuguese version of the SPS-6 displays the
      appropriate structure to measure the active employee's engagement at work.

PMID- 24330217
TI  - Alpha-thalassaemia and response to hydroxyurea in sickle cell anaemia.
AB  - BACKGROUND: Hydroxyurea (HU) reduces vaso-occlusive crises (VOC) and other
      complications of sickle cell anaemia (SCA). Alpha-thalassaemia is a known
      modifier of SCA. Studies on the efficacy of HU in SCA patients with alpha
      thalassaemia have yielded varying results. OBJECTIVE: To determine the effect of
      alpha-thalassaemia in response to HU therapy in the Multicenter Study of
      Hydroxyurea (MSH) cohort. METHODS: We compared the laboratory parameters and VOC
      incidence in the MSH cohort stratified by the presence or the absence of alpha
      thalassaemia. RESULTS: Hydroxyurea showed significant (P = 0.001 for all baseline
      vs. follow-up comparisons) treatment effect on red cell indices irrespective of
      alpha-globin gene deletion. The magnitude of the HU-related changes was similar
      for mean corpuscular volume (MCV) (no alpha-thalassaemia 13 fl and alpha
      thalassaemia 13 fl) and mean corpuscular haemoglobin (MCH) (no alpha-thalassaemia
      4 pg and alpha-thalassaemia 4 pg) in both groups. Foetal haemoglobin (HbF) and F
      cells also increased significantly with HU treatment in both groups. Total
      haemoglobin increased after HU treatment in both groups, but the increase was
      smaller and not statistically significant in patients with alpha-thalassaemia. In
      contrast, HU-related reduction in VOCs was more pronounced in patients with alpha
      thalassaemia (VOC incidence rate ratio HU/placebo: 0.63 for alpha-thalassaemia
      and 0.54 for no alpha-thalassaemia (P for interaction 0.003). CONCLUSION:
      Hydroxyurea decreases VOCs in SCA patients with and without alpha-thalassaemia,
      and the degree of VOC reduction was more pronounced in the patients with alpha
      thalassaemia. Despite the lower baseline values, changes in standard laboratory
      parameters such as MCV and HbF percent remain useful in monitoring HU therapy in
      the presence of alpha-thalassaemia.

PMID- 24330219
TI  - Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis.
AB  - OBJECTIVE: Ultrasonography is sensitive for synovitis detection but interobserver
      variation in both acquisition and image interpretation is still a concern. The
      objective was to assess if a short collegiate consensus would improve inter
      observer reliability in scoring of synovitis. METHODS: Eight rheumatologists
      (Singapore) participated in a 1-day consensus meeting divided into: (i) still
      image interpretation and consensus followed by; (ii) image acquisition and
      interpretation, according to definitions and synovitis scoring rules endorsed by
      Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound
      Initiative). Interobserver reliability of semiquantitative scoring in B-mode,
      Power Doppler (PDUS) and European League Against Rheumatism (EULAR)-OMERACT PDUS
      composite score was assessed by intraclass correlation co-efficient (ICC).
      Agreement at the joint region level was calculated using prevalence-adjusted
      biased-adjusted-kappa (PABAK). RESULTS: For B-mode still images, ICC was good at
      0.75 (95% CI 0.66-0.82) while for PDUS images this was excellent at ICC = 0.88
      (95% CI 0.83-0.92) with ICC improving by 12% for B-mode and 13% for PDUS
      respectively. During image acquisition and interpretation, B-mode scoring showed
      ICC = 0.75 (95% CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95% CI
      0.48-0.72). The ICC for OMERACT PDUS composite synovitis scoring was good at 0.77
      (95% CI 0.68-0.85). At the joint level, agreement varied with PABAK being
      excellent in the small joints of the hands but poor to fair in the wrists,
      elbows, ankles and metatarsophalangeal joints, and no agreement at the knees
      (PABAK range -0.34 to 0.85). CONCLUSION: A consensus meeting was useful in
      improving interobserver variation in US synovitis scoring of still images, but
      image acquisition and interpretation especially in non-hand joints require
      further standardization.

PMID- 24330218
TI  - Allergen hybrids - next generation vaccines for Fagales pollen immunotherapy.
AB  - BACKGROUND: Trees belonging to the order of Fagales show a distinct geographical
      distribution. While alder and birch are endemic in the temperate zones of the
      Northern Hemisphere, hazel, hornbeam and oak prefer a warmer climate. However,
      specific immunotherapy of Fagales pollen-allergic patients is mainly performed
      using birch pollen extracts, thus limiting the success of this intervention in
      birch-free areas. OBJECTIVES: T cells are considered key players in the
      modification of an allergic immune response during specific immunotherapy (SIT),
      therefore we thought to combine linear T cell epitope-containing stretches of the
      five most important Fagales allergens from birch, hazel, alder, oak and hornbeam
      resulting in a Fagales pollen hybrid (FPH) molecule applicable for SIT. METHODS:
      A Fagales pollen hybrid was generated by PCR-based recombination of low IgE
      binding allergen epitopes. Moreover, a structural-variant FPH4 was calculated by
      in silico mutagenesis, rendering the protein unable to adopt the Bet v 1-like
      fold. Both molecules were produced in Escherichia coli, characterized physico
      chemically as well as immunologically, and tested in mouse models of allergic
      sensitization as well as allergy prophylaxis. RESULTS: Using spectroscopic
      analyses, both proteins were monomeric, and the secondary structure elements of
      FPH resemble the ones typical for Bet v 1-like proteins, whereas FPH4 showed
      increased amounts of unordered structure. Both molecules displayed reduced
      binding capacities of Bet v 1-specific IgE antibodies. However, in a mouse model,
      the proteins were able to induce high IgG titres cross-reactive with all parental
      allergens. Moreover, prophylactic treatment with the hybrid proteins prevented
      pollen extract-induced allergic lung inflammation in vivo. CONCLUSION: The hybrid
      molecules showed a more efficient uptake and processing by dendritic cells
      resulting in a modified T cell response. The proteins had a lower IgE-binding
      capacity compared with the parental allergens, thus the high safety profile and
      increased efficacy emphasize clinical application for the treatment of Fagales
      multi-sensitization.

PMID- 24330221
TI  - Pulmonary function changes in rats with taurocholate-induced pancreatitis are
      attenuated by pretreatment with melatonin.
AB  - Melatonin is a free radical scavenger and broad-spectrum antioxidant with
      immunomodulatory effects. We studied the effects of melatonin on changes in lung
      function, oxidative/nitrosative stress, and inflammatory cell sequestration in an
      acute pancreatitis (AP)-associated lung inflammation model. Acute pancreatitis
      was induced by injection of 5% sodium taurocholate into the pancreatic duct of
      rats. Animals were randomized into control, AP, and a melatonin pretreatment (10
      mg/kg)/AP group. Functional residual capacity (FRC), lung compliance (Cchord),
      expiratory flow rate at 50% (FEF50), airway resistance index (RI), and peak
      expiratory flow rate (PEF) were evaluated. White blood cell count (WBC) and
      hydrogen peroxide, lung lavage fluid WBC, methylguanidine, protein, lactic
      dehydrogenase (LDH), nitric oxide (NO), and leukotriene B4 (LTB4) levels were
      determined. Lung wet-to-dry weight ratio, peroxynitrite, and inducible nitric
      oxide synthase (NOS) mRNA and protein were measured. AP induction resulted in
      reductions in FRC, Cchord, FEF50, and PEF, and increase in RI and lung wet-to-dry
      weight ratio. Blood and lung lavage fluid WBC, lavage fluid LDH, protein, and
      blood hydrogen peroxide also increased. Levels of hydroxyl radicals, nitric
      oxide, and LTB4 in lung lavage fluid, inducible NOS mRNA, protein expression, and
      peroxynitrite in lung tissue also were significantly elevated. Pretreatment with
      melatonin attenuated obstructive and restrictive ventilatory insufficiency
      induced by AP. Blood and lavage WBC, lavage LDH and protein, lung edema,
      oxidative/nitrosative stress, and lipoxygenase pathway derivatives were also
      significantly attenuated by melatonin. We conclude that melatonin decreases AP
      induced obstructive and restrictive lung function changes via its antioxidant and
      anti-inflammatory properties. 

PMID- 24330220
TI  - Alabama Veterans Rural Health Initiative: a pilot study of enhanced community
      outreach in rural areas.
AB  - PURPOSE: Access, enrollment, and engagement with primary and specialty health
      care services present significant challenges for rural populations worldwide. The
      Alabama Veterans Rural Health Initiative evaluated an innovative outreach
      intervention combining motivational interviewing, patient navigation, and health
      services education to promote utilization of the United States Veterans
      Administration Healthcare System (VA) by veterans who live in rural locations.
      METHODS: Community outreach workers completed the intervention and assessment,
      enrolling veterans from 31 counties in a southern state. A total 203 participants
      were randomized to either an enhanced enrollment and engagement outreach
      condition (EEE, n = 101) or an administrative outreach (AO, n = 102) condition.
      FINDINGS: EEE participants enrolled and attended VA appointments at higher rates
      and within fewer days than those who received AO. Eighty-seven percent of EEE
      veterans attended an appointment within 6 months, compared to 58% of AO veterans
      (P < .0001). The median time to first appointment was 12 days for the EEE group
      and 98 days for the AO group (P < .0001). Additionally, a race by outreach group
      interaction emerged: black and white individuals benefited equally from the EEE
      intervention; however, black individuals who received AO took significantly
      longer to attend appointments than their white counterparts. CONCLUSIONS: Results
      provide needed empirical support for a specific outreach intervention that speeds
      enrollment and engagement for rural individuals in VA services. Planned
      interventions to improve service utilization should ameliorate ambivalence about
      accessing health care in addition to addressing traditional systems or
      environmental-level barriers.

PMID- 24330222
TI  - Restructuring the Ikeda City school urinary screening system: report of a
      screening survey.
AB  - BACKGROUND: Annual urinary screening is conducted at municipal kindergartens,
      elementary schools, and junior high schools in Ikeda City, Osaka, Japan (Ikeda
      City School System), and the results are reviewed by a general physician, but
      standards for when to recommend specialist referral have not been clear. METHODS:
      In all children attending the Ikeda City School System in 2012, dipstick
      urinalysis of a first-morning urine specimen was recommended once or twice, and
      if a second urinalysis showed proteinuria (>=1+), the urinary protein/creatinine
      ratio was measured. If this showed >=0.2 g/g of creatinine (g/gCr), it was
      recommended that the child be evaluated by a specialist at Ikeda City Hospital.
      RESULTS: Urinary screening was performed in about 20% (388) of kindergarten,
      about 90% (5363) of elementary school, and about 86% (2523) of junior high school
      children living in Ikeda City. Urine samples were obtained from 387, 5349, and
      2476 children, respectively. The urinary protein/creatinine ratio was >=0.2 g/gCr
      in 13 children, including 1 elementary and 12 junior high children. In these 13
      children, chronic nephritic syndrome (CNS) was suspected in 6 junior high school
      children, and of these, this was a new finding in 5, and renal biopsy was
      indicated in 3. In Ikeda City, the prevalence of CNS in elementary school
      children was <0.03%, the prevalence of CNS in junior high school children was
      0.29%, and a renal biopsy was indicated in 0.14%. By eliminating the costs
      associated with assessment of the results by the Ikeda Medical Association, and
      by directly contracting with the testing company, the expenses paid by Ikeda City
      for the system itself decreased from 2,508,619 yen to 966,157 yen. CONCLUSIONS:
      Incorporating the urinary protein/creatinine ratio into the school urinary
      screening system in the Ikeda City School System and clarifying standards for
      specialist referral has enabled restructuring of the system so that is efficient
      and its effectiveness can be assessed.

PMID- 24330223
TI  - Frontiers in epidermal barrier homeostasis--an approach to mathematical modelling
      of epidermal calcium dynamics.
AB  - Intact epidermal barrier function is crucial for survival and is associated with
      the presence of gradients of both calcium ion concentration and electric
      potential. Although many molecules, including ion channels and pumps, are known
      to contribute to maintenance of these gradients, the mechanisms involved in
      epidermal calcium ion dynamics have not been clarified. We have established that
      a variety of neurotransmitters and their receptors, originally found in the
      brain, are expressed in keratinocytes and are also associated with barrier
      homeostasis. Moreover, keratinocytes and neurons show some similarities of
      electrochemical behaviour. As mathematical modelling and computer simulation have
      been employed to understand electrochemical phenomena in brain science, we
      considered that a similar approach might be applicable to describe the dynamics
      of epidermal electrochemical phenomena associated with barrier homeostasis. Such
      methodology would also be potentially useful to address a number of difficult
      problems in clinical dermatology, such as ageing and itching. Although this work
      is at a very early stage, in this essay, we discuss the background to our
      approach and we present some preliminary results of simulation of barrier
      recovery. 

PMID- 24330228
TI  - A systematic review of the effectiveness of CT-guided, lumbar transforaminal
      injection of steroids.
AB  - OBJECTIVE: To determine the effectiveness and safety of computerized tomography
      (CT) guided, lumbar transforaminal injection of steroids in the treatment of
      radicular pain. DESIGN: Systematic review of published literature. INTERVENTIONS:
      Two reviewers independently assessed 19 publications on the effectiveness and
      safety of CT-guided, lumbar transforaminal injection of steroids. OUTCOME
      MEASURES: For effectiveness, the primary outcome was the success rate for relief
      of pain. For safety, the radiation exposure involved and the nature of
      complications were determined. RESULTS: Much of the literature fails to provide
      evidence. Two studies reported decreases in mean or median pain scores but no
      other data. Two studies reported success rates of between 34% and 62% for
      achieving 50% relief of pain at between 1 and 6 months after treatment. CT-guided
      injections may involve greater radiation exposure than does fluoroscopy-guided
      injections and do not avoid catastrophic spinal cord injury. CONCLUSION: The
      evidence-base for CT-guided lumbar transforaminal injection of steroids is
      meagre. This intervention is not more effective than fluoroscopy-guided
      injections and is not demonstrably safer.

PMID- 24330229
TI  - Clinical and resource utilization patterns in patients with refractory
      neuropathic pain prescribed pregabalin for the first time in routine medical
      practice in primary care settings in Spain.
AB  - CONTEXT AND OBJECTIVE: To describe clinical and resource utilization patterns in
      patients with refractory neuropathic pain (NeP) who were prescribed pregabalin
      for the first time in routine medical practice in primary care settings. METHODS:
      Post-hoc analysis of a 12-week prospective observational study including
      pregabalin naive adult patients with refractory chronic NeP of at least 6-months
      duration. Self-reported pain intensity, disability, sleep disturbances, symptoms
      of anxiety and depression, disability, health-related quality of life (HRQoL),
      health care resource utilization, and corresponding costs were assessed in this
      post-hoc analysis. RESULTS: One thousand three hundred fifty-four patients were
      enrolled in the study, and three treatment groups were identified: (1) 598
      patients replaced prior pain treatments with pregabalin as monotherapy; (2) 589
      added pregabalin to their existing pain treatments; and (3) 167 other pain
      treatments were prescribed according with physician routine medical practice.
      Statistically significant differences were reported at baseline for intensity of
      pain, patient disability, severity of depressive symptoms, and HRQoL (P < 0.01 in
      all cases). No statistically significant differences were reported among the
      three treatment groups for anxiety severity or sleep disturbances. Subjects who
      received add-on pregabalin had greater use of direct and indirect resources vs
      the other groups, resulting in significantly higher quarterly overall costs per
      patient: ?2,397 (2,308), ?2,470 (1,857), and ?3,110 (2,496), respectively (P <
      0.001). CONCLUSION: These findings suggest that primary care physicians chose
      pregabalin as an option for treating refractory patients who tended to have much
      more severe NeP profiles, costing society more than when they chose other
      therapeutic strategies not including pregabalin.

PMID- 24330230
TI  - Alopecia due to hair pulling in region of post-herpetic neuralgia-pseudo
      trichotillomania?

PMID- 24330231
TI  - Spatiotemporal changes in the genetic diversity of harmful algal blooms caused by
      the toxic dinoflagellate Alexandrium minutum.
AB  - Organisms with sexual and asexual reproductive systems benefit from both types of
      reproduction. Sexual recombination generates new combinations of alleles, whereas
      clonality favours the spread of the fittest genotype through the entire
      population. Therefore, the rate of sexual vs. clonal reproduction has a major
      influence on the demography and genetic structure of natural populations. We
      addressed the effect of reproductive system on populations of the dinoflagellate
      Alexandrium minutum. More specifically, we monitored the spatiotemporal genetic
      diversity during and between bloom events in two estuaries separated by 150 km
      for two consecutive years. An analysis of population genetic patterns using
      microsatellite markers revealed surprisingly high genotypic and genetic
      diversity. Moreover, there was significant spatial and temporal genetic
      differentiation during and between bloom events. Our results demonstrate that (i)
      interannual genetic differentiation can be very high, (ii) estuaries are
      partially isolated during bloom events and (iii) genetic diversity can change
      rapidly during a bloom event. This rapid genetic change may reflect selective
      effects that are nevertheless not strong enough to reduce allelic diversity.
      Thus, sexual reproduction and/or migration may regularly erase any genetic
      structure produced within estuaries during a bloom event.

PMID- 24330233
TI  - Predictors of outcome in dogs undergoing thoracic surgery (2002-2011).
AB  - OBJECTIVE: To evaluate mortality in a canine population undergoing thoracic
      surgery and identify factors which may be associated with outcome. STUDY DESIGN:
      Retrospective cohort study. ANIMALS: 286 dogs anaesthetized for thoracic surgery
      at the Royal Veterinary College between June 2002 - June 2011. METHODS: Variables
      examined included: signalment; ASA status; nature of disease; presence of co
      morbidities; pre-anaesthetic oxygen requirement; surgical approach; anaesthesia
      management [anaesthetic agents; requirement for thoracocentesis; central venous
      pressure measurement; duration of surgery and anaesthesia; use of colloids, blood
      products, inotropes or neuromuscular blocking agents (NMBA)]. Outcome was defined
      as either non-survival to 24 hours after surgery or (having survived to 24 hours)
      to discharge. Univariate and multivariable logistic regressions were performed to
      identify risk factors associated with non-survival. RESULTS: Overall non-survival
      (excluding those euthanased) to discharge was 5.9%. Non-survival was 2.2% at 24
      hours and 3.6% at time of discharge. Non-survival to 24 hours was associated with
      pre-anaesthetic oxygen requirement (odds ratio (OR) 12.2 [95% CI 1.8-84.5]) and
      NMBA use (OR 9.6 [95% CI 1.6-57.9]). Non-survival to discharge was associated
      with surgical duration, with surgeries >180 minutes having OR 16.9 [95% CI 2.0
      144.0] compared to surgeries <=90 minutes and blood product use (OR 4.6 [95% CI
      1.3-14.6]). No association was found between ASA category and non-survival at 24
      hours (OR 1.4 [95% CI 0.2-11.7]) or discharge (OR 4.4 [95% CI 0.6-34.3]).
      Significant associations were found between NMBA use and ASA category (p =
      0.046), surgical duration (p = 0.002), use of colloids (p = 0.011), blood
      products (p = 0.001) and inotropes and/or vasopressors (p < 0.001). CONCLUSIONS
      AND CLINICAL RELEVANCE: Variables significantly associated with non-survival from
      canine thoracic surgery at 24 hours include NMBA use and pre-anaesthetic oxygen
      requirement. Blood product use and increasing surgical duration were associated
      with non-survival to hospital discharge. The associations may relate to the need
      for such products in the most complicated cases.

PMID- 24330234
TI  - Relaxed trait covariance in interspecific cichlid hybrids predicts morphological
      diversity in adaptive radiations.
AB  - The process of adaptive radiation involves multiple events of speciation in short
      succession, associated with ecological diversification. Understanding this
      process requires identifying the origins of heritable phenotypic variation that
      allows adaptive radiation to progress. Hybridization is one source of genetic and
      morphological variation that may spur adaptive radiation. We experimentally
      explored the potential role of hybridization in facilitating the onset of
      adaptive radiation. We generated first- and second-generation hybrids of four
      species of African cichlid fish, extant relatives of the putative ancestors of
      the adaptive radiations of Lakes Victoria and Malawi. We compared patterns in
      hybrid morphological variation with the variation in the lake radiations. We show
      that significant fractions of the interspecific morphological variation and the
      major trajectories in morphospace that characterize whole radiations can be
      generated in second-generation hybrids. Furthermore, we show that covariation
      between traits is relaxed in second-generation hybrids, which may facilitate
      adaptive diversification. These results support the idea that hybridization can
      provide the heritable phenotypic diversity necessary to initiate adaptive
      radiation. 

PMID- 24330235
TI  - Comparative BAC-based physical mapping of Oryza sativa ssp. indica var. 93-11 and
      evaluation of the two rice reference sequence assemblies.
AB  - Reference sequences are sequences that are used for public consultation, and
      therefore must be of high quality. Using the whole-genome shotgun/next-generation
      sequencing approach, many genome sequences of complex higher plants have been
      generated in recent years, and are generally considered reference sequences.
      However, none of these sequences has been experimentally evaluated at the whole
      genome sequence assembly level. Rice has a relatively simple plant genome, and
      the genome sequences for its two sub-species obtained using different sequencing
      approaches were published approximately 10 years ago. This provides a unique
      system for a case study to evaluate the qualities and utilities of published
      plant genome sequences. We constructed a robust BAC physical map embedding a
      large number of BAC end sequences forrice variety 93-11. Through BAC end sequence
      alignments and tri-assembly comparisons of the 93-11 physical map and the two
      reference sequences, we found that the Nipponbare reference sequence generated
      using the clone-by-clone approach has a high quality but still contains small
      artifact inversions and missing sequences. In contrast, the 93-11 reference
      sequence generated using the whole-genome shotgun approach contains many large
      and varied assembly errors, such as inversions, duplications and translocations,
      as well as missing sequences. The 93-11 physical map provides an invaluable
      resource for evaluation and improvements toward completion of both Nipponbare and
      93-11 reference sequences. 

PMID- 24330236
TI  - Zinc protects human kidney cells from depleted uranium-induced apoptosis.
AB  - Depleted uranium (DU) is a weak radioactive heavy metal, and zinc (Zn) is an
      effective antidote to heavy metal poisoning. However, the effect of Zn on DU
      induced cytotoxicity and apoptosis is not completely understood. The purpose of
      this study was to evaluate the effect of Zn on DU-induced cell apoptosis in human
      kidney cells (HK-2) and explore its molecular mechanism. Pre-treatment with Zn
      significantly inhibited DU-induced apoptosis. It reduced the formation of
      reactive oxygen species in the cells, increased the catalase (CAT) and
      glutathione (GSH) concentrations, suppressed the DU-induced soluble Fas receptor
      (sFasR) and soluble Fas ligand (sFasL) overexpression, suppressed the release of
      cytochrome c and apoptosis inhibitor factor (AIF) from mitochondria to cytoplasm,
      inhibited the activation of caspase-9, caspase-8 and caspase-3, and induced
      metallothionein (MT) expression. Furthermore, exogenous MT effectively inhibited
      DU-induced cell apoptosis. In conclusion, mitochondrial and FasR-mediated
      apoptosis pathways contribute to DU-induced apoptosis in HK-2 cells. Through
      independent mechanisms, such as indirect antioxidant effects, inhibition of the
      activation of caspase-9, caspase-8 and caspase-3, and induction of MT expression,
      Zn inhibits DU-induced apoptosis. 

PMID- 24330237
TI  - Acute angle closure: qualitative and quantitative evaluation of the anterior
      segment using anterior segment optical coherence tomography.
AB  - BACKGROUND: To evaluate different mechanisms of acute angle closure and to
      compare it with unaffected fellow eyes and primary angle closure suspects using
      anterior segment optical coherence tomography. DESIGN: Prospective, cross
      sectional. PARTICIPANTS: 116 eyes (76 patients) with angle closure disease were
      included. METHODS: Eyes were categorized into three groups: (i) acute angle
      closure (40 eyes); (ii) fellow eyes of acute angle closure (40 eyes); and (iii)
      primary angle closure suspect (36 eyes). Complete ophthalmic examinations
      including gonioscopy, A-scan biometry and anterior segment optical coherence
      tomography were performed. MAIN OUTCOME MEASURE: Based on the anterior segment
      optical coherence tomography images, four mechanisms of primary angle closure
      including pupil block, plateau iris configuration, thick peripheral iris roll and
      exaggerated lens vault were evaluated among the three subtypes of angle closure
      disease. RESULTS: There was a statistically significant difference in the
      mechanism of angle closure disease among the three groups (P < 0.001). Although
      the majority of fellow and primary angle closure suspect eyes had pupil block
      mechanism (77.5% and 75%, respectively), only 37.5% of acute angle closure eyes
      had dominant pupil block mechanism. The percentage because of exaggerated lens
      vault was greatest in acute angle closure eyes (50%). Acute angle closure eyes
      had the shallowest anterior chamber depth (P < 0.001), least iris curvature (P <
      0.001) and greatest lens vault (P = 0.003) compared with the other two groups.
      CONCLUSIONS: A statistically significant difference in the underlying primary
      angle closure mechanisms among acute angle closure eyes as compared with their
      fellow eyes and primary angle closure suspect may exist.

PMID- 24330238
TI  - Commentary: daily pantoprazole vs. esomeprazole for GERD.

PMID- 24330239
TI  - Commentary: anaemia in inflammatory bowel disease--the most common and ignored
      extra intestinal manifestation.

PMID- 24330240
TI  - Commentary: daily pantoprazole vs. esomeprazole for GERD--authors' reply.

PMID- 24330241
TI  - Letter: PPI-responsive oesophageal eosinophilia--from initial scepticism to
      consistent prospective data.

PMID- 24330242
TI  - Letter: PPI-responsive oesophageal eosinophilia--from initial skepticism to
      consistent prospective data; authors' reply.

PMID- 24330243
TI  - Letter: Epstein-Barr virus status may be especially important in paediatric IBD
      populations.

PMID- 24330244
TI  - Letter: dermatological complications with therapy for inflammatory bowel disease.

PMID- 24330245
TI  - Letter: dermatological complications with therapy for inflammatory bowel disease-
      authors' reply.

PMID- 24330246
TI  - Letter: follow-up practices in coeliac disease--intestinal biopsy after child-to
      adult transition might be useful.

PMID- 24330247
TI  - Letter: follow-up practices in coeliac disease--intestinal biopsy after child-to
      adult transition might be useful; authors' reply.

PMID- 24330248
TI  - Letter: biochemical response to combination anti-retroviral therapy in patients
      with primary biliary cirrhosis.

PMID- 24330249
TI  - Feeling at home from arrival to departure: protein export and host cell
      remodelling during Plasmodium liver stage and gametocyte maturation.
AB  - Obligate intracellular pathogens actively remodel their host cells to boost
      propagation, survival, and persistence. Plasmodium falciparum, the causative
      agent of the most severe form of malaria, assembles a complex secretory system in
      erythrocytes. Export of parasite factors to the erythrocyte membrane is essential
      for parasite sequestration from the blood circulation and a major factor for
      clinical complications in falciparum malaria. Historic and recent molecular
      reports show that host cell remodelling is not exclusive to P. falciparum and
      that parasite-induced intra-erythrocytic membrane structures and protein export
      occur in several Plasmodia. Comparative analyses of P. falciparum asexual and
      sexual blood stages and imaging of liver stages from transgenic murine Plasmodium
      species show that protein export occurs in all intracellular phases from liver
      infection to sexual differentiation, indicating that mammalian Plasmodium species
      evolved efficient strategies to renovate erythrocytes and hepatocytes according
      to the specific needs of each life cycle phase. While the repertoireof identified
      exported proteins is remarkably expanded in asexual P. falciparum blood stages,
      the putative export machinery and known targeting signatures are shared across
      life cycle stages. A better understanding of the molecular mechanisms underlying
      Plasmodium protein export could assist in designing novel strategies to interrupt
      transmission between Anopheles mosquitoes and humans. 

PMID- 24330250
TI  - Effects of substituting a portion of standard physiotherapy time with virtual
      reality games among community-dwelling stroke survivors.
AB  - BACKGROUND: Evidence indicates that the continuation of therapy among community
      dwelling stroke survivors improves physical function. Community rehabilitation
      programmes often face limitations in terms of resources. It is imperative to
      include new motivational interventions to encourage some level of non-clinician
      management. The aim of this study was to determine whether there were any changes
      in physical function and activities of daily living when substituting a portion
      of the standard physiotherapy time with virtual reality games among community
      dwelling stroke survivors. METHODS: In this controlled trial, the experimental
      group received 30 minutes of virtual reality balance games in addition to 90
      minutes of standard physiotherapy. The control group continued with their two
      hours of routine standard physiotherapy. Both groups received 12 therapy
      sessions: two-hour sessions twice per week for six continuous weeks. Changes in
      physical function, activities of daily living and balance ability were assessed
      using the Timed Up and Go test, 30-second Sit to Stand test, Timed Ten-Metre Walk
      test, Six-Minute Walk test and the Barthel Index, and static balance was assessed
      using a probalance board. RESULTS: Twenty-eight participants completed post
      intervention assessments. The results showed a significant within-subject effect
      on the Timed Up and Go test: F (1, 26) = 5.83, p = 0.02; and the 30-second Sit to
      Stand test; F (1, 26) = 13.50, p = 0.001. The between-subject effect was not
      significant (p > 0.05) for any of the outcome measurements. CONCLUSION:
      Substituting a portion of the standard physiotherapy time with virtual reality
      games was equally effective in maintaining physical function outcomes and
      activities of daily living among community-dwelling stroke survivors. TRIAL
      REGISTRATION: Australia and New Zealand Clinical Trials Register,
      ACTRN12613000478718.

PMID- 24330251
TI  - Hand and heart, hand in hand: is radiological hand osteoarthritis associated with
      atherosclerosis?
AB  - AIM: Increasing evidence suggests that atherosclerosis contributes to the
      initiation or progression of osteoarthritis (OA). It has been suggested that
      atherosclerosis may cause vascular insufficiency which may lead to or progress
      OA. In this study, the association between the severity of radiologic hand OA and
      atherosclerosis was analyzed in women. METHODS: Sixty-one women, >= 50 years of
      age, free of hand symptoms were enrolled in the study. Postero-anterior views of
      both hands were obtained using digital radiography. A total of 14 joints were
      assessed for radiographic OA according to Kellgren/Lawrence (K/L) score. An OA
      affected joint was defined as K/L score of >= 2. Hand OA was defined as >= 3
      joints of both hands affected with OA and severity of hand OA was defined as
      total K/L scores of all 14 joints of both hands. Gensini scoring was used to
      evaluate the patients for atherosclerosis severity. RESULTS: The patient
      characteristics such as presence of diabetes, smoking, hypertension, dyslipidemia
      and medications used were similar for patients with and without hand OA (P >
      0.05) and did not correlate with Gensini or hand OA scores. The mean Gensini
      scores of patients with hand OA was 21.5 +/- 17.1 and without hand OA was 11.8 +/
      9.2 (P = 0.017). The degree of osteoarthritic joint involvement and Gensini
      scores showed a positive correlation (r = 0.332, P = 0.009). CONCLUSION: Hand OA
      may be a benign clinical finding that may suggest a possible serious underlying
      atherosclerosis. Patients with significant hand OA should be screened for
      atherosclerosis to prevent serious coronary artery disease and related
      comorbidities.

PMID- 24330253
TI  - Hypotheses, rationale, design, and methods for evaluation of ischemic
      preconditioning assessed by sequential exercise tests in diabetic and non
      diabetic patients with stable coronary artery disease--a prospective study.
AB  - BACKGROUND: Ischemic preconditioning is a powerful mechanism of myocardial
      protection and in humans it can be evaluated by sequential exercise tests.
      Coronary Artery Disease in the presence of diabetes mellitus may be associated
      with worse outcomes. In addition, some studies have shown that diabetes
      interferes negatively with the development of ischemic preconditioning. However,
      it is still unknown whether diabetes may influence the expression of ischemic
      preconditioning in patients with stable multivessel coronary artery disease.
      METHODS/DESIGN: This study will include 140 diabetic and non-diabetic patients
      with chronic, stable coronary artery disease and preserved left ventricular
      systolic function. The patients will be submitted to two sequential exercise
      tests with 30-minutes interval between them. Ischemic parameters will be compared
      between diabetic and non-diabetic patients. Ischemic preconditioning will be
      considered present when time to 1.0 mm ST-segment deviation is greater in the
      second of two sequential exercise tests. Exercise tests will be analyzed by two
      independent cardiologists. DISCUSSION: Ischemic preconditioning was first
      demonstrated by Murry et al. in dog's hearts. Its work was reproduced by other
      authors, clearly demonstrating that brief periods of myocardial ischemia followed
      by reperfusion triggers cardioprotective mechanisms against subsequent and severe
      ischemia. On the other hand, the demonstration of ischemic preconditioning in
      humans requires the presence of clinical symptoms or physiological changes
      difficult to be measured. One methodology largely accepted are the sequential
      exercise tests, in which, the improvement in the time to 1.0 mm ST depression in
      the second of two sequential tests is considered manifestation of ischemic
      preconditioning.Diabetes is an important and independent determinant of clinical
      prognosis. It's a major risk factor for coronary artery disease. Furthermore, the
      association of diabetes with stable coronary artery disease imposes worse
      prognosis, irrespective of treatment strategy. It's still not clearly known the
      mechanisms responsible by these worse outcomes. Impairment in the mechanisms of
      ischemic preconditioning may be one major cause of this worse prognosis, but, in
      the clinical setting, this is not known. The present study aims to evaluate how
      diabetes mellitus interferes with ischemic preconditioning in patients with
      stable, multivessel coronary artery disease and preserved systolic ventricular
      function.

PMID- 24330252
TI  - Chronic CRF1 receptor blockade reduces heroin intake escalation and dependence
      induced hyperalgesia.
AB  - Opioids represent effective drugs for the relief of pain, yet chronic opioid use
      often leads to a state of increased sensitivity to pain that is exacerbated
      during withdrawal. A sensitization of pain-related negative affect has been
      hypothesized to closely interact with addiction mechanisms. Neuro-adaptive
      changes occur as a consequence of excessive opioid exposure, including a
      recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain
      stress systems. To better understand the mechanisms underlying the transition to
      dependence, we determined the effects of functional antagonism within these two
      systems on hyperalgesia-like behavior during heroin withdrawal utilizing models
      of both acute and chronic dependence. We found that passive or self-administered
      heroin produced a significant mechanical hypersensitivity. During acute opioid
      dependence, systemic administration of the CRF1 receptor antagonist MPZP (20
      mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast,
      several functional adrenergic system antagonists (clonidine, prazosin,
      propranolol) failed to alter mechanical hypersensitivity in this state. We then
      determined the effects of chronic MPZP or clonidine treatment on extended access
      heroin self-administration and found that MPZP, but not clonidine, attenuated
      escalation of heroin intake, whereas both drugs alleviated chronic dependence
      associated hyperalgesia. These findings suggest that an early potentiation of CRF
      signaling occurs following opioid exposure that begins to drive both opioid
      induced hyperalgesia and eventually intake escalation. 

PMID- 24330254
TI  - A phylogenomic approach to bacterial subspecies classification: proof of concept
      in Mycobacterium abscessus.
AB  - BACKGROUND: Mycobacterium abscessus is a rapidly growing mycobacterium that is
      often associated with human infections. The taxonomy of this species has
      undergone several revisions and is still being debated. In this study, we
      sequenced the genomes of 12 M. abscessus strains and used phylogenomic analysis
      to perform subspecies classification. RESULTS: A data mining approach was used to
      rank and select informative genes based on the relative entropy metric for the
      construction of a phylogenetic tree. The resulting tree topology was similar to
      that generated using the concatenation of five classical housekeeping genes:
      rpoB, hsp65, secA, recA and sodA. Additional support for the reliability of the
      subspecies classification came from the analysis of erm41 and ITS gene sequences,
      single nucleotide polymorphisms (SNPs)-based classification and strain clustering
      demonstrated by a variable number tandem repeat (VNTR) assay and a multilocus
      sequence analysis (MLSA). We subsequently found that the concatenation of a
      minimal set of three median-ranked genes: DNA polymerase III subunit alpha
      (polC), 4-hydroxy-2-ketovalerate aldolase (Hoa) and cell division protein FtsZ
      (ftsZ), is sufficient to recover the same tree topology. PCR assays designed
      specifically for these genes showed that all three genes could be amplified in
      the reference strain of M. abscessus ATCC 19977T. CONCLUSION: This study provides
      proof of concept that whole-genome sequence-based data mining approach can
      provide confirmatory evidence of the phylogenetic informativeness of existing
      markers, as well as lead to the discovery of a more economical and informative
      set of markers that produces similar subspecies classification in M. abscessus.
      The systematic procedure used in this study to choose the informative minimal set
      of gene markers can potentially be applied to species or subspecies
      classification of other bacteria.

PMID- 24330255
TI  - Risk of non-melanoma skin cancer in myasthenia patients treated with
      azathioprine.
AB  - BACKGROUND AND PURPOSE: The association between use of azathioprine and risk of
      non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a
      nationwide setting. Treatment of autoimmune myasthenia frequently involves long
      term exposure to immunosuppressants, including azathioprine. Use of azathioprine
      increases the risk of NMSC in organ recipients and probably also in patients with
      other autoimmune disorders. No previous study has specifically investigated the
      risk of NMSC in myasthenia patients treated with azathioprine. METHODS: This is a
      case-control study based on Danish population-based registries. Cases were
      myasthenia patients with a first time diagnosis of NMSC during 2004-2009. Age-
      and sex-matched controls were selected amongst myasthenia patients with no
      history of cancer using incidence density sampling. Prior use of azathioprine in
      cases and controls was assessed through prescription records (1995-2009).
      Conditional logistic regression was used to calculate odds ratios (OR) with 95%
      confidence intervals (CI) for skin cancer associated with a high cumulative dose
      (>=150 g) or long-term use (>=5 years) of azathioprine, adjusted for confounders.
      RESULTS: Thirty NMSC cases and 360 matched controls were identified. Ever use of
      azathioprine was associated with a considerably increased risk of NMSC (OR 3.3,
      95% CI 1.5-7.3) that was even more apparent in patients with high cumulative dose
      (OR 4.6, 95% CI 1.7-12.5) or long-term (OR 4.8; 95% CI 1.7-13.6) use of
      azathioprine. CONCLUSION: Azathioprine use in patients with myasthenia is
      associated with an increased risk of NMSC.

PMID- 24330256
TI  - Low gut microbiota diversity in early infancy precedes asthma at school age.
AB  - BACKGROUND: Low total diversity of the gut microbiota during the first year of
      life is associated with allergic diseases in infancy, but little is known how
      early microbial diversity is related to allergic disease later in school age.
      OBJECTIVE: To assess microbial diversity and characterize the dominant bacteria
      in stool during the first year of life in relation to the prevalence of different
      allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis
      (ARC) and eczema. METHODS: The microbial diversity and composition was analysed
      with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and
      12 months of age in 47 infants which were subsequently assessed for allergic
      disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID
      NCT01285830). RESULTS: Children developing asthma (n = 8) had a lower diversity
      of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1
      month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema
      (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not
      associate with the gut microbiota diversity. Neither was asthma associated with
      the microbiota composition later in infancy (at 12 months). Children having IgE
      associated eczema in infancy and subsequently developing asthma had lower
      microbial diversity than those that did not. There were no significant
      differences, however, in relative abundance of bacterial phyla and genera between
      children with or without allergic disease. CONCLUSION AND CLINICAL RELEVANCE: Low
      total diversity of the gut microbiota during the first month of life was
      associated with asthma but not ARC in children at 7 years of age. Measures
      affecting microbial colonization of the infant during the first month of life may
      impact asthma development in childhood.

PMID- 24330257
TI  - Association of chronic nasal symptoms with dyspnoea and quality-of-life
      impairment in chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Previous studies suggested that chronic nasal symptoms
      (CNS) are frequent in chronic obstructive pulmonary disease (COPD) subjects, but
      their contribution to dyspnoea and quality-of-life (QoL) impairment is not
      clearly established. METHODS: Data from the French COPD cohort 'Initiatives
      bronchopneumopathie chronique obstructive' were analyzed to assess the frequency
      of CNS (rhinorrhea, obstruction, anosmia) in COPD patients and analyze their
      impact and associated risk factors. Univariate and multivariate analyses were
      performed to assess the relationship between CNS with sociodemographic and
      anthropometric characteristics, risk factors, respiratory symptoms, spirometry,
      QoL (Saint George's respiratory questionnaire (SGRQ)), dyspnoea (modified Medical
      Research Council (mMRC) scale), mood disorders (Hospital Anxiety and Depression
      Scale (HADS)), number of exacerbations and comorbid conditions. RESULTS: CNS were
      reported by 115 of 274 COPD subjects (42%). Among them, rhinorrhea and nasal
      obstruction were reported by 62% and 43%, respectively. In multivariate analysis,
      COPD patients with CNS had higher SGRQ total scores, corresponding to worse QoL
      (P = 0.01), while no independent association was found with exacerbations, lung
      function and HADS. Among SGRQ domains, an independent association was found with
      the activity score (P = 0.007). When SGRQ score was forced out of the model to
      avoid redundancy, mMRC score was independently associated with CNS (P = 0.01).
      Among risk factors, cumulative smoking, hay fever and atopic dermatitis but not
      occupational exposures were independently associated with CNS. CONCLUSIONS: In
      this group of COPD subjects, CNS were frequently observed and associated with
      dyspnoea and poorer QoL. CNS should be systematically assessed and could be a
      potential target in the management of COPD.

PMID- 24330258
TI  - Detection of alpha(0)-thalassemia South-East Asian-type deletion by droplet
      digital PCR.
AB  - BACKGROUND: The alpha(0)-thalassemia South-East Asian (SEA)-type deletion is the
      most common genetic disorder in the Asian population. Couples who are both
      carriers have a 25% chance of conceiving Bart's hydrops fetalis. Therefore,
      results from carrier screening and prenatal diagnosis frequently need to be
      available rapidly. The aim of this study was to implement a droplet digital
      polymerase chain reaction (ddPCR) for diagnosis of alpha(0)-thalassemia SEA-type
      deletion. METHODS: The wild-type alpha-globin gene allele and alpha(0)
      thalassemia SEA allele were quantified in DNA samples of 20 normal individuals,
      15 samples with alpha(0)-thalassemia SEA trait, and 8 samples with Bart's hydrops
      fetalis using the ddPCR. The DNA copy number of wild-type alpha-globin gene
      allele and alpha(0)-thalassemia SEA allele was then calculated using the
      Quantasoft analysis software. RESULTS: The mean +/- standard deviation (SD) ratio
      of wild-type alpha-globin gene allele and alpha(0)-thalassemia SEA allele among
      normal individuals, samples with alpha(0)-thalassemia SEA trait, and Bart's
      hydrops fetalis were clearly distinguished with levels of 1.78 +/- 0.49, 0.85 +/-
      0.14, and 0.03 +/- 0.03, respectively. CONCLUSION: The ddPCR may be one
      alternative technology available for routine clinical diagnosis of alpha(0)
      thalassemia SEA-type deletion and prenatal diagnosis of Bart's hydrops fetalis.

PMID- 24330259
TI  - The equitable allocation of deceased donor lungs for transplant in children in
      the United States.
AB  - On June 5, 2013, a US Federal Court ordered a temporary restraining order to
      allow two children within the court's jurisdiction to be registered on the
      adolescent lung transplant waiting list. On June 10, 2013, the Organ Procurement
      and Transplantation Network's Executive Committee altered lung allocation policy
      to offer candidates aged younger than 12 years greater access to adult lungs at
      the discretion of the national Lung Review Board. The Scientific Registry of
      Transplant Recipients reviewed trends over time in deceased donor lung transplant
      waitlist mortality and transplant rates, comparing children and adults. Mortality
      rates of candidates active on the waiting list have been higher for children aged
      0-5 years, but have not differed for children aged 6-11 years compared with
      adolescents aged 12-17 years or adults aged 18 years or older. Transplant rates
      among active waitlist candidates have been comparable across all age groups.
      Thus, there is little evidence that the allocation system led to differences in
      waitlist mortality or transplant rates for children compared with adults.
      However, these comparisons are difficult to interpret given that current policies
      likely led to unaccounted differences in the severity of illness at the time of
      listing. 

PMID- 24330261
TI  - Effect of community size on eligibility for early intervention for infants with a
      neonatal intensive care experience.
AB  - PURPOSE: To determine if population density (rural vs urban) in a child's home
      community influenced the decision of eligibility for early intervention (EI)
      services. METHODS: The sample included 356 infants with a gestational age of <31
      weeks referred from a statewide child find program for an evaluation for EI
      services. A binary logistic regression analysis was completed to determine which
      variables predicted acceptance into EI services. FINDINGS: Infants less than 31
      weeks gestation residing in rural areas were more likely to be eligible for EI
      services than premature infants (ie, <31 weeks gestation) with similar birth
      characteristics from urban areas. A binary logistic regression analysis revealed
      an odds ratio for eligibility for EI services among children living in rural
      areas compared to those living in urban areas was 3.007 (95% CI, 1.497 to 6.040).
      Additionally, the odds ratio for eligibility for males as compared to females was
      1.908 (95% CI, 1.017 to 3.578). Participants who lived in a rural area and were
      male were more likely to be eligible for EI services than those who lived in
      urban locations and were female. CONCLUSIONS: Factors such as community support,
      experience with high-risk populations, and differences in interpreting
      eligibility criteria may influence the differences found between the rural and
      urban populations. Analysis of intervention cost versus effectiveness will be
      needed to determine whether the system as adopted in the rural versus urban
      environment is more appropriate for the provision of EI services.

PMID- 24330260
TI  - Enzymes involved in plastid-targeted phosphatidic acid synthesis are essential
      for Plasmodium yoelii liver-stage development.
AB  - Malaria parasites scavenge nutrients from their host but also harbour enzymatic
      pathways for de novo macromolecule synthesis. One such pathway is apicoplast
      targeted type II fatty acid synthesis, which is essential for late liver-stage
      development in rodent malaria. It is likely that fatty acids synthesized in the
      apicoplast are ultimately incorporated into membrane phospholipids necessary for
      exoerythrocytic merozoite formation. We hypothesized that these synthesized fatty
      acids are being utilized for apicoplast-targeted phosphatidic acid synthesis, the
      phospholipid precursor. Phosphatidic acid is typically synthesized in a three
      step reaction utilizing three enzymes: glycerol 3-phosphate dehydrogenase,
      glycerol 3-phosphate acyltransferase and lysophosphatidic acid acyltransferase.
      The Plasmodium genome is predicted to harbour genes for both apicoplast- and
      cytosol/endoplasmic reticulum-targeted phosphatidic acid synthesis. Our research
      shows that apicoplast-targeted Plasmodium yoelii glycerol 3-phosphate
      dehydrogenase and glycerol 3-phosphate acyltransferase are expressed only during
      liver-stage development and deletion of the encoding genes resulted in late liver
      stage growth arrest and lack of merozoite differentiation. However, the predicted
      apicoplast-targeted lysophosphatidic acid acyltransferase gene was refractory to
      deletion and was expressed solely in the endoplasmic reticulum throughout the
      parasite life cycle. Our results suggest that P. yoelii has an incomplete
      apicoplast-targeted phosphatidic acid synthesis pathway that is essential for
      liver-stage maturation.

PMID- 24330262
TI  - Successful treatment of hereditary multiple glomangiomas with Nd:YAG laser.

PMID- 24330263
TI  - First-in-human trial of nanoelectroablation therapy for basal cell carcinoma:
      proof of method.
AB  - This nanoelectroablation therapy effectively treats subdermal murine allograft
      tumors, autochthonous basal cell carcinoma (BCC) tumors in Ptch1+/-K14-Cre-ER p53
      fl/fl mice, and UV-induced melanomas in C57/BL6 HGF/SF mice. Here, we described
      the first human trial of this modality. We treated 10 BCCs on three subjects with
      100-1000 electric pulses 100 ns in duration, 30 kV/cm in amplitude, applied at 2
      pulses per second. Seven of the 10 treated lesions were completely free of
      basaloid cells when biopsied and two partially regressed. Two of the 7 exhibited
      seborrheic keratosis in the absence of basaloid cells. One of the 10 treated
      lesions recurred by week 10 and histologically had the appearance of a squamous
      cell carcinoma. No scars were visible at the healed sites of any of the
      successfully ablated lesions. One hundred pulses were sufficient for complete
      ablation of BCCs with a single, 1-min nanoelectroablation treatment. 

PMID- 24330264
TI  - Comparison of an infrared anaesthetic agent analyser (Datex-Ohmeda) with
      refractometry for measurement of isoflurane, sevoflurane and desflurane
      concentrations.
AB  - OBJECTIVE: To assess agreement between infrared (IR) analysers and a
      refractometer for measurements of isoflurane, sevoflurane and desflurane
      concentrations and to demonstrate the effect of customized calibration of IR
      analysers. STUDY DESIGN: In vitro experiment. SUBJECTS: Six IR anaesthetic
      monitors (Datex-Ohmeda) and a single portable refractometer (Riken). METHODS:
      Both devices were calibrated following the manufacturer's recommendations. Gas
      samples were collected at common gas outlets of anaesthesia machines. A range of
      agent concentrations was produced by stepwise changes in dial settings:
      isoflurane (0-5% in 0.5% increments), sevoflurane (0-8% in 1% increments), or
      desflurane (0-18% in 2% increments). Oxygen flow was 2 L minute(-1) . The orders
      of testing IR analysers, agents and dial settings were randomized. Duplicate
      measurements were performed at each setting. The entire procedure was repeated 24
      hours later. Bland-Altman analysis was performed. Measurements on day-1 were used
      to yield calibration equations (IR measurements as dependent and refractometry
      measurements as independent variables), which were used to modify the IR
      measurements on day-2. RESULTS: Bias +/- limits of agreement for isoflurane,
      sevoflurane and desflurane were 0.2 +/- 0.3, 0.1 +/- 0.4 and 0.7 +/- 0.9 volume%,
      respectively. There were significant linear relationships between differences and
      means for all agents. The IR analysers became less accurate at higher gas
      concentrations. After customized calibration, the bias became almost zero and the
      limits of agreement became narrower. CONCLUSIONS AND CLINICAL RELEVANCE: If
      similar IR analysers are used in research studies, they need to be calibrated
      against a reference method using the agent in question at multiple calibration
      points overlapping the range of interest.

PMID- 24330265
TI  - MHC class I molecules are incorporated into human herpesvirus-6 viral particles
      and released into the extracellular environment.
AB  - Human herpesvirus-6 (HHV-6), which belongs to the betaherpesvirus subfamily,
      mainly replicates in T lymphocytes. Here, we show that MHC class I molecules are
      incorporated into HHV-6 viral particles and released into the extracellular
      environment. In addition, HHV-6A/B-infected T cells showed reduced surface and
      intracellular expression of MHC class I molecules. The cellular machinery
      responsible for molecular transport appears to be modified upon HHV-6 infection,
      causing MHC class I molecules to be transported to virion assembly sites. 

PMID- 24330266
TI  - Methane and carbon at equilibrium in source rocks.
AB  - Methane in source rocks may not exist exclusively as free gas. It could exist in
      equilibrium with carbon and higher hydrocarbons: CH4 + C < = > Hydrocarbon. Three
      lines of evidence support this possibility. 1) Shales ingest gas in amounts and
      selectivities consistent with gas-carbon equilibrium. There is a 50% increase in
      solid hydrocarbon mass when Fayetteville Shale is exposed to methane (450 psi)
      under moderate conditions (100 degrees C): Rock-Eval S2 (mg g-1) 8.5 = > 12.5.
      All light hydrocarbons are ingested, but with high selectivity, consistent with
      competitive addition to receptor sites in a growing polymer. Mowry Shale ingests
      butane vigorously from argon, for example, but not from methane under the same
      conditions. 2) Production data for a well producing from Fayetteville Shale
      declines along the theoretical curve for withdrawing gas from higher hydrocarbons
      in equilibrium with carbon. 3) A new general gas-solid equilibrium model accounts
      for natural gas at thermodynamic equilibrium, and C6-C7 hydrocarbons constrained
      to invariant compositions. The results make a strong case for methane in
      equilibrium with carbon and higher hydrocarbons. If correct, the higher
      hydrocarbons in source rocks are gas reservoirs, raising the possibility of
      substantially more gas in shales than analytically apparent, and far more gas in
      shale deposits than currently recognized. 

PMID- 24330267
TI  - Pneumonia in children: more shadows than lights.

PMID- 24330268
TI  - International guidelines on tackling community-acquired pneumonia show major
      discrepancies between developed and developing countries.
AB  - AIM: The goal of this study was to compare the current guidelines on diagnosis
      and treatment of paediatric community-acquired pneumonia (CAP) in developing and
      developed countries. METHODS: A literature search was performed consulting the
      Medline, Embase, Current Contents, National Guideline Clearinghouse and Cochrane
      database, from January 2000 to March 2013. RESULTS: Twelve guidelines were
      selected: six from developed countries and six from developing countries. Major
      discrepancies between the diagnosis and treatment approaches recommended by
      guidelines covering developing and developed countries were revealed. The search
      also highlighted differences between recommendations issued in similar settings.
      CONCLUSION: The guidelines show wide variations and weak recommendations and
      further research is needed to improve clinical outcomes and make better use of
      resources.

PMID- 24330269
TI  - Diagnostic features of community-acquired pneumonia in children: what's new?
AB  - AIM: To critically summarise the available data on diagnosis of CAP in children,
      focusing on the newest findings and on the need for new studies. METHODS: Eighty
      studies on the diagnosis of paediatric community-acquired pneumonia were
      scrutinised. RESULTS: We found no significant associations between the signs or
      symptoms and aetiology of pneumonia and concluded that chest radiographs remain
      controversial and real-time polymerase chain reaction appears more sensitive than
      blood cultures. CONCLUSION: Antibiotic overuse could make it difficult to
      differentiate viral and bacterial causes. Molecular methods provide promising
      tools for diagnosing infection by atypical bacteria, but are expensive and should
      be used selectively.

PMID- 24330270
TI  - Treating paediatric community-acquired pneumonia in the era of antimicrobial
      resistance.
AB  - Increasing levels of paediatric community-acquired pneumonia (CAP), caused by
      drug-resistant bacteria and antimicrobial resistance, vary with age and countries
      and, in some cases, serotypes. When empirical first-line treatment administration
      fails, paediatricians should consider second-line treatments based on the
      prevalence of local resistance. A more judicious use of antimicrobial agents is
      also required. CONCLUSION: Knowledge of local epidemiology and an appropriate use
      of antimicrobial drugs are necessary to treat CAP in this era of antimicrobial
      resistance.

PMID- 24330271
TI  - Two-stage surgery for hidradenitis suppurativa: staged artificial dermis and skin
      grafting.
AB  - BACKGROUND: Hidradenitis suppurativa is a chronic and often refractory skin
      disease that can require radical excision of the full layer of fatty tissue under
      the lesion. Closure using a split-thickness skin graft often results in
      depression deformity and lack of tissue flexibility. We have developed a two
      stage procedure to preserve fatty tissue during radical excision and apply an
      artificial dermis graft, and we have performed this procedure in 18 patients (33
      lesions). OBJECTIVE: To describe our two-stage procedure and report results of
      the procedure in our patient series. METHODS: In the first step, all diseased
      skin including the superficial subcutaneous fatty tissue is excised; normal deep
      subcutaneous fatty tissue is preserved. Artificial dermis is then grafted to the
      preserved fatty tissue. Two weeks later, split-thickness skin grafts are applied
      to the skin defects. We evaluated graft success, any recurrence, and
      postoperative appearance in our patients, who were followed up for 8 to 36
      months. RESULTS: All 32 skin grafts were successful. There was only one
      recurrence, which was treated using reoperation, and postoperative appearances
      were good. CONCLUSIONS: Our new procedure incorporating artificial dermis appears
      to be a good treatment option for advanced hidradenitis suppurativa.

PMID- 24330272
TI  - Precise plant breeding using new genome editing techniques: opportunities, safety
      and regulation in the EU.
AB  - Several new plant breeding techniques (NPBTs) have been developed during the last
      decade, and make it possible to precisely perform genome modifications in plants.
      The major problem, other than technical aspects, is the vagueness of regulation
      concerning these new techniques. Since the definition of eight NPBTs by a
      European expert group in 2007, there has been an ongoing debate on whether the
      resulting plants and their products are covered by GMO legislation. Obviously,
      cover by GMO legislation would severely hamper the use of NPBT, because
      genetically modified plants must pass a costly and time-consuming GMO approval
      procedure in the EU. In this review, we compare some of the NPBTs defined by the
      EU expert group with classical breeding techniques and conventional transgenic
      plants. The list of NPBTs may be shortened (or extended) during the international
      discussion process initiated by the Organization for Economic Co-operation and
      Development. From the scientific point of view, it may be argued that plants
      developed by NPBTs are often indistinguishable from classically bred plants and
      are not expected to possess higher risks for health and the environment. In light
      of the debate on the future regulation of NPBTs and the accumulated evidence on
      the biosafety of genetically modified plants that have been commercialized and
      risk-assessed worldwide, it may be suggested that plants modified by crop genetic
      improvement technologies, including genetic modification, NPBTs or other future
      techniques, should be evaluated according to the new trait and the resulting end
      product rather than the technique used to create the new plant variety. 

PMID- 24330273
TI  - Prolidase deficiency breaks tolerance to lupus-associated antigens.
AB  - AIM: Prolidase deficiency is a rare autosomal recessive disease in which one of
      the last steps of collagen metabolism, cleavage of proline-containing dipeptides,
      is impaired. Only about 93 patients have been reported with about 10% also having
      systemic lupus erythematosus (SLE). METHODS: We studied a large extended Amish
      pedigree with four prolidase deficiency patients and three heterozygous
      individuals for lupus-associated autoimmunity. Eight unaffected Amish children
      served as normal controls. Prolidase genetics and enzyme activity were confirmed.
      Antinuclear antibodies (ANA) were determined using indirect immunofluorescence
      and antibodies against extractable nuclear antigens were determined by various
      methods, including double immunodiffusion, immunoprecipitation and multiplex bead
      assay. Serum C1q levels were determined by enzyme-linked immunosorbent assay.
      RESULTS: Two of the four homozygous prolidase deficiency subjects had a positive
      ANA. One had anti-double-stranded DNA, while another had precipitating anti-Ro.
      By the simultaneous microbead assay, three of the four had anti-Sm and anti
      chromatin. One of the three heterozygous subjects had a positive ANA and
      immunoprecipitation of a 75 000 molecular weight protein. The unaffected controls
      had normal prolidase activity and were negative for autoantibodies. CONCLUSIONS:
      Prolidase deficiency may be associated with the loss of immune tolerance to lupus
      associated autoantigens even without clinical SLE.

PMID- 24330275
TI  - Regeneration of the dentine-pulp complex with revitalization/revascularization
      therapy: challenges and hopes.
AB  - The concept of regenerative endodontics has gained much attention in clinical
      endodontics in the past decade. One aspect of this discipline is the application
      of revitalization/revascularization therapies for infected and/or necrotic
      immature pulps in permanent teeth. Following the publication of a case report
      (Iwaya et al. ), investigators have been rigorously examining the types of
      tissues formed in the canals as well as exploring strategies to regenerate the
      pulp-dentine complex in revitalized teeth. This review will provide an update on
      the types of tissues generated in the canals after
      revitalization/revascularization therapy in both animal and human studies. The
      understanding of the role of stem cells and microenvironment in the process of
      wound healing resulting in either regeneration or repair will be thoroughly
      discussed. Stem cells and microenvironmental cues introduced into the canal
      during revitalization/revascularization procedures will be examined. In addition,
      requirement of a sterile microenvironment in the canal and vital tissue
      generation in revitalization/revascularization therapy will be emphasized. The
      challenges that we face and the hopes that we have in
      revitalization/revascularization therapy for regenerative endodontics will be
      presented. 

PMID- 24330274
TI  - Local adaptation with high gene flow: temperature parameters drive adaptation to
      altitude in the common frog (Rana temporaria).
AB  - Both environmental and genetic influences can result in phenotypic variation.
      Quantifying the relative contributions of local adaptation and phenotypic
      plasticity to phenotypes is key to understanding the effect of environmental
      variation on populations. Identifying the selective pressures that drive
      divergence is an important, but often lacking, next step. High gene flow between
      high- and low-altitude common frog (Rana temporaria) breeding sites has
      previously been demonstrated in Scotland. The aim of this study was to assess
      whether local adaptation occurs in the face of high gene flow and to identify
      potential environmental selection pressures that drive adaptation. Phenotypic
      variation in larval traits was quantified in R. temporaria from paired high- and
      low-altitude sites using three common temperature treatments. Local adaptation
      was assessed using Q(ST)-F(ST) analyses, and quantitative phenotypic divergence
      was related to environmental parameters using Mantel tests. Although evidence of
      local adaptation was found for all traits measured, only variation in larval
      period and growth rate was consistent with adaptation to altitude. Moreover, this
      was only evident in the three mountains with the highest high-altitude sites.
      This variation was correlated with mean summer and winter temperatures,
      suggesting that temperature parameters are potentially strong selective pressures
      maintaining local adaptation, despite high gene flow.

PMID- 24330276
TI  - Reversible abnormality of the splenium in a bipolar patient with neuroleptic
      malignant syndrome.
AB  - OBJECTIVE: To report reversible abnormality of the splenium in a bipolar patient
      with neuroleptic malignant syndrome (NMS). METHODS: We studied a 23-year-old male
      who received oral and parenteral neuroleptics, atypical antipsychotic agents, and
      mood stabilizers, as well as a course of six electroconvulsive therapy
      treatments, for an episode of mania. He improved. Five days after discharge on
      maintenance atypical antipsychotic agents and mood stabilizers, he returned with
      symptoms suggestive of NMS. Laboratory investigations revealed leucopenia,
      thrombocytopenia, and elevated creatine phosphokinase levels. Brain magnetic
      resonance imaging showed swelling of the splenium with centrally restricted
      diffusion; there was no other abnormality. He was defensively treated with
      antimicrobials, methylprednisolone, and bromocriptine. RESULTS: Clinical recovery
      was complete after nine days, and the splenium lesion resolved after four further
      days; there were no neuropsychiatric sequelae. Nine months later, the patient
      remains well on maintenance lithium therapy. CONCLUSIONS: This is the first
      report of an isolated splenial lesion reversing within days of resolution of NMS.
      The outcome supports the recent literature which suggests that an isolated
      splenial lesion does not need investigation, and that prognosis depends on the
      underlying disorder, and not on the presence or absence of the splenial lesion.

PMID- 24330277
TI  - Antivascular endothelial growth factors in the treatment of macular oedema
      secondary to central retinal vein occlusion: a meta-analysis.
AB  - BACKGROUND: Macular oedema secondary to central retinal vein occlusion is a major
      cause of vision loss. Intraocuclar anti-vascular endothelial growth factor
      injection is a promising treatment but lacks clinical evidence of its safety and
      efficacy. DESIGN: Meta-analysis. PARTICIPANTS: Patients from previously reported
      randomized, controlled trials comparing intravitreal anti-vascular endothelial
      growth factor versus sham injections. METHODS: A comprehensive search in MEDLINE,
      CENTRAL, and EMBASE was conducted for reports published by April 2013. A meta
      analysis of the retrieved data was conducted in RevMan 5.2 software. MAIN OUTCOME
      MEASURES: Primary outcome measures were changes in best-corrected visual acuity
      and central retinal thickness from baseline. Secondary outcome measures were the
      proportion of eyes changing 15 or more letters on the Early Treatment in Diabetic
      Retinopathy Study chart, the proportion with neovascularization and changes in
      the 25-item Visual Function Questionnaire. Severe adverse events were summarized
      to assess safety. RESULTS: Six trials involving a total of 940 eyes were included
      in the meta-analysis. The mean difference in 6-month changes in best-corrected
      visual acuity and central retinal thickness for the anti-vascular endothelial
      growth factor group were 15.2 Early Treatment Diabetic Retinopathy Study letters
      (P < 0.00001) and -242.2 MUm (P < 0.00001), respectively. Severe adverse event
      incidence was similar between the groups. CONCLUSIONS: Intravitreal anti-vascular
      endothelial growth factor injections were safe and effective for macular oedema
      secondary to central retinal vein occlusion. The efficacy was rapid and robust.
      Further trials are needed to determine the detailed indications and therapeutic
      regimens of anti-vascular endothelial growth factor treatments.

PMID- 24330278
TI  - Prevention in primary care: facilitators and barriers to transform prevention
      from a random coincidence to a systematic approach.
AB  - RATIONALE, AIMS AND OBJECTIVES: The Dutch general practitioner (GP) plays a
      substantial role in prevention. At the same time, many GPs hesitate to
      incorporate large-scale cardiovascular risk management (CVRM) programmes into
      their daily practice. By exploring facilitators and barriers occurring during the
      past three decades, we wish to find clues on how to motivate professionals to
      adopt and implement prevention programmes. METHODS: A witness seminar was
      organized in September 2011, inviting key figures to discuss the decision-making
      process of the implementation of systematic prevention programmes in the
      Netherlands in the past, thereby adding new perspectives on past events. The
      extensive discussion was fully audiotaped. The transcript was content-analysed.
      RESULTS: We came across four different transitional stages: (1) the conversion
      from GPs disputing prevention to the implementation of systematic influenza
      vaccination; (2) the transition from systematic influenza vaccination to planning
      CVRM programmes; (3) the transition from planning and piloting CVRM programmes to
      cancelling the large-scale implementation of the CVRM programme; and (4) the
      reinforcement of prevention. CONCLUSIONS: The GPs' fear to lose the domain of
      prevention to other health care professionals and financial and logistical
      support are the main facilitators for implementing prevention programmes in
      primary care. The main barriers for implementing prevention are the combination
      of insecurity about reimbursement and lack of scientific evidence. It appears
      that the ethical view of GPs that everyone should have the same right to obtain
      preventive care gradually takes over the inclination to hold on to evidence-based
      prevention.

PMID- 24330279
TI  - Changes in prevalence of prescription opioid abuse after introduction of an abuse
      deterrent opioid formulation.
AB  - OBJECTIVE: The reformulation of oxycodone hydrochloride controlled-release (CR)
      tablets in August 2010 created a natural experiment at a national scale,
      providing an opportunity to evaluate patterns of abuse of prescription opioids
      and other drugs before and after introduction of this abuse-deterrent formulation
      (ADF). DESIGN: Observational, cross-sectional study SETTING: Sentinel sample of
      adults assessed for substance abuse treatment within the NAVIPPRO(r) surveillance
      system SUBJECTS: Two hundred thirty-two thousand and eight hundred seventy-four
      adults at 437 facilities during January 1, 2008 through December 31, 2011.
      METHODS: Time-series analysis using logistic regression to estimate quarterly
      prevalence of past 30-day abuse (adjusted for covariates and prescription volume)
      and changes in abuse pre-and post-ADF introduction. RESULTS: Increases in abuse
      prevalence occurred for all prescription opioids as a class and for extended
      release (ER) opioids. Significantly greater abuse of ER oxymorphone and
      buprenorphine occurred in the post-ADF period (relative risk [RR] = 2.91, 95%
      confidence interval [CI] = 2.59-3.27 and RR = 1.85, 95% CI = 1.74-1.96).
      Increases in abuse for these two compounds were significant among groups who
      reported abuse via preferential routes of administration (oral only, snorting
      only, injection only) post-ADF introduction. CONCLUSIONS: Replacement of a widely
      prescribed opioid formulation known for its abuse potential alone may have had
      little impact on overall rates of prescription opioids as a class. However,
      changes in abuse levels of certain opioids coinciding with ADF introduction
      suggest possible switching of abuse among this study sample to specific long
      acting opioid analgesics. Additional follow-up studies will be important to
      monitor changing abuse patterns and their public health impact as new opioid
      formulations are developed and introduced to market.

PMID- 24330280
TI  - The effect of aggressive rosuvastatin treatment on steroid hormone production in
      men with coronary artery disease.
AB  - Most steroid hormones are produced from cholesterol contained in low-density
      lipoproteins, which is uptaken by the gonads and adrenal cortex, and used as a
      substrate for steroidogenesis. Theoretically, in states associated with very low
      density lipoprotein (LDL) cholesterol levels, cholesterol conversion to steroid
      hormones may be impaired. The study included 15 men with coronary artery disease,
      in whom initial statin treatment had been unsuccessful and therefore was replaced
      with rosuvastatin (20-40 mg daily). Although in 11 patients, rosuvastatin
      decreased plasma LDL cholesterol levels to below 70 mg/dL, the drug only
      moderately reduced testosterone levels and increased gonadotropin levels, as well
      as insignificantly increased plasma ACTH levels. Aggressive rosuvastatin
      treatment did not affect plasma cortisol and dehydroepiandrosterone sulphate
      levels, and urine free cortisol. Our results suggest that intensive rosuvastatin
      treatment is associated with only small changes in adrenal and testicular
      steroidogenesis. 

PMID- 24330281
TI  - Detection of human herpesviruses in the cerebrospinal fluid from patients
      diagnosed with or suspected of having progressive multifocal leukoencephalopathy.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML), a fatal
      demyelinating disease caused by JC virus (JCV), occurs mainly in
      immunocompromised patients. While JCV DNA is detected in the cerebrospinal fluid
      (CSF) from a certain proportion of patients suspected of having PML, JCV-negative
      patients may also develop brain lesions due to other infectious agents. This
      study assessed the prevalence of six herpesviruses in the CSF from patients
      diagnosed with or suspected of PML. METHODS: Two hundred and ninety-nine CSF
      specimens and clinical data were collected from 255 patients, including 31
      confirmed PML cases. Quantitative PCR assays were carried out to detect the
      genomic DNA of JCV, herpes simplex virus (HSV), varicella-zoster virus (VZV),
      cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6).
      RESULTS: Herpesvirus DNAs were detected in the CSF specimens from 29 of 255
      patients (11.4%). HSV-1 and CMV were detected in JCV-negative patients, whereas
      VZV and EBV were detected in both CSF JCV-positive and -negative individuals. The
      herpesvirus-positive patients had underlying disorders that caused
      immunosuppression, such as HIV infection, congenital immunodeficiencies, and
      hematologic malignancies, and presented with neurologic symptoms and MRI lesions,
      mainly in the cerebral white matter. The median values of CSF cell counts and
      protein levels in the herpesvirus-positive patients were slightly higher than
      those in the PML patients. CONCLUSIONS: The results demonstrate that
      herpesviruses are occasionally detected in the CSF from PML patients and
      immunocompromised individuals suspected of having PML. Thus, this study provides
      a significant basis for the diagnosis and treatment of neurological disorders in
      immunocompromised patients.

PMID- 24330283
TI  - Acute coronary syndrome in young Sub-Saharan Africans: a prospective study of 21
      cases.
AB  - BACKGROUND: Coronary heart disease remains the leading cause of death in
      developed countries. In Africa, the disease continues to rise with varying rates
      of progression in different countries. At present, there is little available work
      on its juvenile forms. The objective of this work was to study the
      epidemiological, clinical and evolutionary aspects of acute coronary syndrome in
      young Sub-Saharan Africans. METHODS: This was a prospective multicenter study
      done at the different departments of cardiology in Dakar. We included all
      patients of age 40 years and below, and who were admitted for acute coronary
      syndrome between January 1st, 2005 and July 31st, 2007. We collected and analyzed
      the epidemiological, clinical, paraclinical and evolutionary data of the
      patients. RESULTS: Hospital prevalence of acute coronary syndrome in young people
      was 0.45% (21/4627) which represented 6.8% of all cases of acute coronary
      syndrome admitted during the same period. There was a strong male predominance
      with a sex-ratio (M:F) of 6. The mean age of patients was 34 +/- 1.9 years (range
      of 24 and 40 years). The main risk factor was smoking, found in 52.4% of cases
      and the most common presenting symptom was chest pain found in 95.2% of patients.
      The average time delay before medical care was 14.5 hours. Diagnosis of ST
      elevation myocardial infarction in 85.7% of patients and non-ST-elevation
      myocardial infarction in 14.3% was made by the combination electrocardiographic
      features and troponin assay. Echocardiography found a decreased left ventricular
      systolic function in 37.5% of the patients and intraventricular thrombus in 20%
      of them. Thrombolysis using streptokinase was done in 44.4% of the patients with
      ST-elevation myocardial infarction. Hospital mortality was 14.3%. CONCLUSION:
      Acute coronary syndrome is present in young Sub-Saharan Africans. The main risk
      factor found was smoking.

PMID- 24330282
TI  - Age-associated bidirectional modulation of gene expression in single identified
      R15 neuron of Aplysia.
AB  - BACKGROUND: Despite the advances in our understanding of aging-associated
      behavioral decline, relatively little is known about how aging affects neural
      circuits that regulate specific behaviors, particularly the expression of genes
      in specific neural circuits during aging. We have addressed this by exploring a
      peptidergic neuron R15, an identified neuron of the marine snail Aplysia
      californica. R15 is implicated in reproduction and osmoregulation and responds to
      neurotransmitters such as acetylcholine, serotonin and glutamate and is
      characterized by its action potential bursts. RESULTS: We examined changes in
      gene expression in R15 neurons during aging by microarray analyses of RNAs from
      two different age groups, mature and old animals. Specifically we find that 1083
      ESTs are differentially regulated in mature and old R15 neurons. Bioinformatics
      analyses of these genes have identified specific biological pathways that are up
      or downregulated in mature and old neurons. Comparison with human signaling
      networks using pathway analyses have identified three major networks [(1) cell
      signaling, cell morphology, and skeletal muscular system development (2) cell
      death and survival, cellular function maintenance and embryonic development and
      (3) neurological diseases, developmental and hereditary disorders] altered in old
      R15 neurons. Furthermore, qPCR analysis of single R15 neurons to quantify
      expression levels of candidate regulators involved in transcription (CREB1) and
      translation (S6K) showed that aging is associated with a decrease in expression
      of these regulators, and similar analysis in three other neurons (L7, L11 and R2)
      showed that gene expression change during aging could be bidirectional.
      CONCLUSIONS: We find that aging is associated with bidirectional changes in gene
      expression. Detailed bioinformatics analyses and human homolog searches have
      identified specific biological processes and human-relevant signaling pathways in
      R15 that are affected during aging. Evaluation of gene expression changes in
      different neurons suggests specific transcriptomic signature of single neurons
      during aging.

PMID- 24330284
TI  - Acute scrotum in Kawasaki disease: two case reports and a literature review.
AB  - Acute scrotum is a rare complication of acute Kawasaki disease (KD), less well
      recognized than other disease manifestations. We describe the cases of two
      patients, aged 59 months and 19 months, with hydrocele testis in the acute phase
      of KD. Scrotal ultrasound and trans-illumination were used in the diagnosis of
      hydrocele testis. One patient underwent eventual surgical intervention. We
      reviewed the literature for a better understanding of the pathogenesis of scrotal
      symptoms in acute KD and investigated the clinical importance of hydrocele
      testis. Careful further clinical observation may elucidate the true incidence of
      this extracardiac symptoms, thereby clarifying the diagnostic value of this
      possible complication in acute KD. 

PMID- 24330285
TI  - VLCAD deficiency in a patient who recovered from ventricular fibrillation, but
      died suddenly of a respiratory syncytial virus infection.
AB  - VLCAD deficiency is an autosomal recessive disorder caused by a defect of fatty
      acid oxidation. The phenotype is classified into three clinical forms on the
      basis of the onset of symptoms: a severe form with neonatal onset; a milder form
      with childhood onset; and a late-onset form. The neonatal form is the most
      common, and has a higher mortality rate than the others. We report the case of a
      newborn infant with VLCAD deficiency who developed ventricular fibrillation,
      which was successfully treated by intensive care, but who suddenly died after a
      respiratory syncytial virus infection. Early institution of i.v. glucose
      treatment and active immunization with vaccine, such as palivizumab (anti-RSV
      mAb), may be important to reduce the frequency and severity of life-threatening
      episodes. 

PMID- 24330286
TI  - Transverse myelitis and acute motor sensory axonal neuropathy due to Legionella
      pneumophila: a case report.
AB  - Guillain-Barre syndrome is a rapidly progressive symmetrical muscle weakness
      associated with acute inflammatory disease. Transverse myelitis (TM) is the
      inflammation of the spinal cord characterized by rapidly evolving muscle weakness
      in the lower extremities, defects in sensory level and sphincter dysfunction.
      Guillain-Barre syndrome, and TM association occurs very rarely in childhood. A 7
      year-old girl presented with complaints of neck pain, spout-style vomiting,
      cough, shortness of breath, and acute paraparesis with sensory and sphincter
      disturbance. The patient was intubated because of increased respiratory distress.
      A positive direct fluorescein antigen test in bronchoalveolar lavage confirmed
      Legionella pneumophila infection. Imaging and neurophysiologic studies were
      diagnostic for TM with acute motor and sensory axonal neuropathy. She was treated
      with a combination of high-dose methylprednisolone and intravenous
      immunoglobulins, and we observed incomplete recovery. The presented case is the
      first child with concomitant TM and acute motor and sensory axonal neuropathy
      related to L. pneumophila infection.

PMID- 24330287
TI  - Continuous glucose monitoring for suspected dumping syndrome in infants after
      Nissen fundoplication.
AB  - Dumping syndrome is infrequently reported, but known to occur after Nissen
      fundoplication in children. However, it may be difficult both to diagnose and
      manage. Here we presented four infants who received Nissen fundoplication for
      severe gastroesophageal reflux disease, two of whom developed dumping syndrome
      whilst the other two did not. Continuous glucose monitoring (CGM) was very useful
      to clearly detect large glycemic fluctuation around each feeding. CGM was also
      helpful to prove the effect of treatment to avoid abnormal glucose levels. We
      believe that dumping syndrome in children may be underdiagnosed if clinicians
      rely solely on the recognition of symptoms or limited frequency of blood
      samplings. CGM might be the most sensitive diagnostic tool. 

PMID- 24330288
TI  - Case of cytomegalovirus-associated direct anti-globulin test-negative autoimmune
      hemolytic anemia.
AB  - A 1-year-old boy developed autoimmune hemolytic anemia after a negative direct
      anti-globulin test. The concentration of erythrocyte membrane-associated
      immunoglobulin G, determined using an immunoradiometric assay, correlated with
      disease activity. He was positive for cytomegalovirus (CMV) both serologically
      and by quantitative real-time polymerase chain reaction, indicating that his
      autoimmune hemolytic anemia was directly caused by CMV infection. Since anti-CMV
      immunoglobulin G was not absorbed by the patient's erythrocytes, cross-reaction
      between erythrocyte antigens and CMV was not likely a causative factor for
      hemolysis. 

PMID- 24330289
TI  - Hemolytic uremic syndrome related to cryptosporidium infection in an
      immunocompetent child.
AB  - Hemolytic-uremic syndrome (HUS) is characterized by the clinical and laboratory
      manifestations of acute renal failure, thrombocytopenia and microangiopathic
      hemolytic anemia. In children, the majority of cases occur after an infectious
      diarrhea mainly associated with the serotype Escherichia coli O157:H7. We present
      a case of a 5-year-old boy with post-diarrhea HUS due to cryptosporidium. The
      child remained on peritoneal dialysis for 24 days. However, he had a full
      recovery of his renal function and 6 months later, his overall condition was
      still very good. This is a particularly interesting case, not only due to the
      exceptionally rare cause of HUS, that is, the cryptosporidium, but also because
      of the serious gastroenteritis caused by the cryptosporidium in an
      immunocompetent child. It seems that in cases of post-diarrhea HUS, apart from E.
      coli O157:H7, even the rarest causes of gastroenteritis should be investigated.

PMID- 24330290
TI  - Remarkably delayed occurrence of normal surfactant composition in an extremely
      preterm infant.
AB  - Reported herein is the first case of a remarkably delayed occurrence of normal
      surfactant composition in an extremely preterm infant who required a total of 15
      doses of artificial pulmonary surfactant (Surfacten(r)). A male infant, born at
      26 weeks gestation, developed respiratory distress at birth. Chest radiography
      was consistent with respiratory distress syndrome. The infant required repeated
      doses of surfactant, each resulting in transient periods of decreased ventilator
      requirement and improved blood gas values. Surfactant proteins (SP)-A, SP-B, SP
      C, and SP-D from tracheal aspirate samples were analyzed on the 13th day
      (deterioration period) and 36th day (recovery period) after birth. On the 13th
      day sufficient SP-A and SP-D but no SP-B no SP-C were detected on western blot
      analysis. SP-B and SP-C were eventually detected on the 36th day. This infant
      therefore required almost 3 months to achieve normal surfactant function.

PMID- 24330291
TI  - Acute alcohol intoxication in a 15-day-old neonate.
AB  - We describe a 15-day-old newborn girl who was fed with formula milk that was
      accidentally diluted with sake (Japanese wine prepared from fermented rice). The
      clinical features were flushed skin, tachycardia and low blood pressure
      indicating circulatory failure, somnolence and metabolic acidosis without
      hypoglycemia. The serum ethanol concentration was 43.0 mg/dL at 3 h after intake.
      The patient recovered under intravenous fluid replacement without complications.
      Follow-up examinations at 1, 2, 3, 6 and 12 months confirmed normal psychomotor
      development.

PMID- 24330292
TI  - Paraovarian cyst torsion in children: report of two cases.
AB  - Paraovarian cysts are assumed to be rare in childhood. This assumption is due to
      the fact that most patients with paraovarian cyst are asymptomatic unless
      complicated. Owing to the wide range of pathologies in differential diagnosis,
      preoperative diagnosis of paraovarian cyst presents a challenge. Herein is
      reported two cases of complicated paraovarian cyst in children. 

PMID- 24330293
TI  - Social prejudice hindering proper use of car safety seats.
AB  - The compliance of parents with child passenger safety (CPS) has been mainly
      explained by their level of knowledge. Social, ethnic and cultural factors have
      not been investigated in detail. This study investigated the rate of compliance
      of parents with CPS guidelines, as well as the factors hindering it. Parents of
      infants aged 2-10 days were enrolled. The proportions of families obtaining a car
      safety seat (CSS; 57%) and complying with CPS recommendations (2%) were very low.
      Most of the parents thought CSS were harmful for infants (mother, 57%; father,
      63%), despite having already purchased one. Parents believed their children to be
      too small to use CSS and cannot sit in CSS because they should lie flat on their
      backs at all times. These prejudices may be due to the social and cultural
      circumstances specific to Turkey, or corresponding findings may be found in
      countries with similar socioeconomic status. 

PMID- 24330294
TI  - Development of Kawasaki disease in a patient with PFAPA.
AB  - Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome
      (PFAPA) is one of the autoinflammatory diseases of unknown etiology characterized
      by regularly recurrent fever episodes with attacks lasting 3-6 days every 3-8
      weeks associated with at least one of the three cardinal clinical signs: aphthous
      stomatitis, pharyngitis, and cervical adenitis. Kawasaki disease (KD) is an
      acute, self-limited systemic vasculitis that occurs predominantly in infants and
      young children. In most KD patients, i.v. immunoglobulin leads to a rapid
      amelioration of clinical symptoms and significantly decreases the risk of
      coronary artery aneurysms. Although the etiology of KD is still unknown, it was
      reported that innate immunity was activated in the patients. Described herein is
      a patient with PFAPA who developed KD. This is the first report of KD development
      in a PFAPA patient. The association between KD and PFAPA may represent a genetic
      predisposition to dysregulated innate immune response. 

PMID- 24330295
TI  - Use of non-invasive total hemoglobin measurement as a screening tool for anemia
      in children.
AB  - Universal screening for anemia is important in children, but invasive blood
      sampling is required. A new device (Radical-7(r) Pulse CO-OximeterTM, Masimo,
      Irvine, CA, USA) now enables non-invasive hemoglobin concentration (SpHb)
      measurement to be done, but the usefulness of this device for anemia screening in
      children is unclear. The objective of this study was to compare SpHb with
      complete blood count (CBC) using a hematology analyzer (Microsemi(r) LC-667CRP;
      Fukuda Denshi, Tokyo, Japan). SpHb measurement with Radical-7(r) was done as part
      of a medical check-up in 3-year-old children (n = 110). Another 43 pediatric
      patients were checked for CBC using Microsemi(r) and monitored with Radical-7(r).
      The mean SpHb level of the 3-year-old children was 12.1 +/- 0.64 g/dL (range,
      10.8-13.7 g/dL). The correlation of Radical-7(r) and Microsemi(r) was 0.602 (P <
      0.0001). On Bland-Altman comparison, bias was -0.6 +/- 1.1 g/dL. Even though
      further improvement is required, Radical-7(r) offers many possibilities in the
      context of primary screening.

PMID- 24330296
TI  - Glycogenic hepatopathy and non-alcoholic fatty liver disease in type 1 diabetes
      patients.

PMID- 24330298
TI  - Decreased sialylation of IgA1 O-glycans associated with pneumococcal hemolytic
      uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) in children is usually caused by Shiga-like toxin
      producing Escherichia coli, but approximately 5% of cases are caused by invasive
      pneumococcal infection (P-HUS). Reported herein is the case of a 9-month-old HUS
      patient with pneumococcal meningitis who needed hemodialysis for 12 days.
      Decreased sialylation was characterized in both transferrin N-glycans and IgA1 O
      glycans, analyzed in the acute phase on mass spectrometry, consistent with S.
      pneumonia-produced sialidases hydrolyzing both alpha2,3- and alpha2,6-linked
      sialic acids. The method will complement the T-antigen activation test and help
      to understand the molecular pathology related to P-HUS.

PMID- 24330299
TI  - Intramuscular anti-D in chronic immune thrombocytopenia children with severe
      thrombocytopenia.
AB  - Nine patients with chronic immune thrombocytopenia and platelet counts <20 *
      10(9) /L, with a median age of 7.8 (3.8-15.5) years, received three phases of 10
      mcg/kg/dose of intramuscular anti-D. Phase 1 was anti-D daily for 5 days,
      followed by phase 2, anti-D weekly for 12 weeks and withheld when platelet counts
      >= 20 * 10(9) /L, and then phase 3 was anti-D once every 2 weeks for 24 weeks.
      According to the International Working Group criteria, in phase 1, 66.7% of
      patients responded to the treatment. In phases 2 and 3, 11.1% (0-41.7%) and 7.7%
      (0-33.3%) of total episodes of follow up, respectively, responded to the
      treatment. Therefore, intramuscular anti-D given at a dose of 10 mcg/kg for 5
      days is an alternative method to raise platelet counts in chronic immune
      thrombocytopenia children with severe thrombocytopenia where the intravenous form
      of anti-D is not available.

PMID- 24330300
TI  - Fulminant form of acute disseminated encephalomyelitis in a child treated with
      mild hypothermia.
AB  - We describe the case of a 3-year-old boy diagnosed with the fulminant form of
      acute disseminated encephalomyelitis (ADEM). He developed general fatigue, fever,
      drowsiness and difficulty in walking. He had extensive multiple high-intensity
      lesions in the white matter of the cerebrum and cerebellum, which are typical
      findings of ADEM. He became comatose and developed decerebrate rigidity with
      severe brain edema despite high-dose methylprednisolone therapy, and then was
      subjected to mild hypothermia therapy, and given i.v. immunoglobulin. The patient
      recovered remarkably with the sequela of only mild action tremor. The patient was
      considered to have acute hemorrhagic leukoencephalitis (AHLE), an extremely
      severe form of ADEM, in terms of the rapidly deteriorating clinical course and
      neuroimaging features. It was speculated that AHLE and ADEM might be a continuous
      disease spectrum. It is considered that the severe brain edema associated with
      ADEM or AHLE is a suitable indication for mild hypothermia therapy. 

PMID- 24330301
TI  - Infantile splenorenopancreatic mucormycosis complicating neuroblastoma.
AB  - Herein is described the first case of an infant with neuroblastoma who developed
      isolated splenorenopancreatic mucormycosis. An 18-month-old boy with
      neuroblastoma who was on intensive chemotherapy was admitted with febrile
      neutropenia. On abdominal computed tomography, multiple hypodense lesions in the
      spleen with invasion to the upper pole of the left kidney were demonstrated.
      Enlargement of splenic lesions with a complete hypoechoic pattern replacing the
      whole spleen, consistent with splenic abscess were observed on serial ultrasound.
      On splenectomy the resected spleen appeared to be severely fragmented and
      necrotic. On pathology, massive infiltration of broad, non-septate hyphal
      fragments identified as Mucor with invasion to all blood vessels was seen.
      Histologically, a piece of the tail of the pancreas also showed involvement by
      the filamentous Mucor. The present case highlights the necessity of high index of
      suspicion in susceptible patients, early diagnosis and appropriate management in
      order to minimize the mortality rate.

PMID- 24330302
TI  - Asymptomatic methylmalonic acidemia in a homozygous MUT mutation (p.P86L).
AB  - Deficiency in methylmalonyl-coenzyme A mutase (MCM) is associated with
      accumulation of methylmalonic acid (MMA) and clinical outcomes that include early
      death and neurological impairment. Reported here are two unrelated patients with
      a homozygous p.P86L mutation in the MUT gene, which encodes MCM, diagnosed
      following newborn screening. This is the first description of a homozygous
      mutation in the N-terminal extended segment of the MCM apoenzyme. Both in vitro
      and in vivo testing did not find a response to supplemental hydroxocobalamin.
      After discontinuation of hydroxocobalamin in one patient, serum MMA level
      remained elevated but stable, while urine MMA increased. Both patients have
      remained asymptomatic with normal development. The observed homozygous p.P86L
      mutation in the N-terminal extended segment may yield reduced MCM activity and is
      refractory to hydroxocobalamin supplementation, while not inducing a
      metabolically unstable phenotype. These genotype-phenotype associations further
      enhance the understanding of methylmalonic acidemia, which will continue to
      improve patient care. 

PMID- 24330303
TI  - Apnea with RSV infection in three infants receiving palivizumab.
AB  - The present report describes three infants receiving palivizumab prophylaxis who
      presented with apnea associated with respiratory syncytial virus (RSV) infection.
      All three were found to be RSV positive but had mild bronchiolitis courses. Even
      though palivizumab has been shown to be an effective prophylaxis in preventing
      RSV bronchiolitis hospitalizations, its effect on apnea is unknown. The cases
      presented raise the concern that apnea associated with RSV must still be
      considered in infants who receive proper prophylaxis with palivizumab. Also, if
      palivizumab is found to be ineffective in preventing apnea, clinical management
      of these patients could be altered.

PMID- 24330305
TI  - Notch signaling in melanoma: interacting pathways and stromal influences that
      enhance Notch targeting.
AB  - The Notch signaling pathway is an evolutionarily conserved, intercellular
      signaling cascade. Notch was first described in the early 1900s when a mutant
      Drosophila showed notches on the wing margins. Studies of the role of Notch
      signaling have ever since flourished, and the pleiotropic nature of the Notch
      gene is now evident. Indeed, the Notch signaling pathway plays key roles in cell
      fate decisions, tissue patterning, and morphogenesis during development. However,
      deregulation of this pathway can contribute to cell transformation and
      tumorigenesis. Several reports have now highlighted the role of Notch signaling
      in a variety of malignancies where Notch can either be an oncogene or a tumor
      suppressor depending on the cell context. Here, we summarize the major components
      of Notch signaling with an aim to emphasize the contribution of deregulated Notch
      signaling in melanomagenesis. 

PMID- 24330304
TI  - Treatment of cartilage-hair hypoplasia with recombinant human growth hormone.
AB  - Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder characterized
      by short stature, hypoplastic hair and humoral immunity disorders. It is a
      mutation in the RMRP gene, located on chromosome 9p13.3, that leads to CHH. There
      is no special treatment for short stature in CHH. The efficacy and safety of
      recombinant human growth hormone (rhGH) therapy in CHH is still under discussion.
      The present study describes the case of a girl with CHH who was treated with
      rhGH. The rhGH treatment had a significant effect on the height gain: the height
      SD score was changed from -4. to -2.98 after 4 years 7 months of treatment. rhGH
      therapy should be considered as a treatment modality for CHH, and insulin-like
      growth factor (IGF)-1 and IGF-binding protein 3 concentrations should be closely
      monitored, particularly because of the increased cancer risk that is a
      characteristic feature of CHH.

PMID- 24330306
TI  - Amyloid burden correlates with cognitive decline in Alzheimer's disease
      presenting with aphasia.
AB  - BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD)
      present with early and prominent language deficits. It is unclear whether the
      burden of underlying beta-amyloid pathology is associated with language or
      general cognitive impairment in these subjects. METHODS: The relationship between
      cortical beta-amyloid burden on [(11) C]Pittsburgh compound B (PiB) positron
      emission tomography (PET) and performance on the Montreal Cognitive Assessment
      (MoCA), the Wechsler Memory Scale - Third Edition (WMS-III), the Boston Naming
      Test (BNT) and the Western Aphasia Battery (WAB) was assessed using regression
      and correlation analyses in subjects presenting with aphasia who showed beta
      amyloid deposition on PiB PET. RESULTS: The global PiB ratio was inversely
      correlated with MoCA (P = 0.02) and the WMS-III Visual Reproduction (VR) subtest
      (VR I, P = 0.02; VR II, P = 0.04). However, the correlations between PiB ratio,
      BNT (P = 0.13), WAB aphasia quotient (P = 0.11) and WAB repetition scores (P =
      0.34) were not significant. CONCLUSION: This study demonstrates that an increased
      cortical beta-amyloid burden is associated with cognitive impairment, but not
      language deficits, in AD subjects presenting with aphasia. The results suggest
      that beta-amyloid deposition could be partly contributing to impaired cognition
      in such patients whilst language dysfunction may be more influenced by other
      pathological mechanisms, perhaps downstream pathways of beta-amyloid deposition.

PMID- 24330307
TI  - Making decisions about treatment for young people diagnosed with depressive
      disorders: a qualitative study of clinicians' experiences.
AB  - BACKGROUND: The imperative to provide effective treatment for young people
      diagnosed with depressive disorders is complicated by several factors including
      the unclear effectiveness of treatment options. Within this context, little is
      known about how treatment decisions are made for this population. METHODS: In
      order to explore the experiences and beliefs of clinicians about treatment
      decision making for this population, semi-structured, qualitative interviews were
      conducted with 22 psychiatrists, general practitioners and allied health
      professionals from health care settings including specialist mental health
      services and primary health care. Interviews were audio taped, transcribed
      verbatim and analysed using thematic analysis. RESULTS: Clinicians largely
      reported and endorsed a collaborative model of treatment decision making for
      youth depression, although several exceptions to this approach were also
      described (e.g., when risk issues were present), highlighting a need to adapt the
      decision-making style to the characteristics and needs of the client. A
      differentiation was made between the decision-making processes (e.g., sharing of
      information) and who makes the decision. Caregiver involvement was seen as
      optional, especially in situations where no caregivers were involved, but ideal
      and useful if the caregivers were supportive. Gaps between the type and amount of
      information clinicians wanted to give their clients and what they actually gave
      them were reported (e.g., having fact sheets on hand). A broad range of barriers
      to involving clients and caregivers in decision-making processes were described
      relating to four levels (client and caregiver, clinician, service and broader
      levels) and suggestions were given to help overcome these barriers, including up
      to-date, accessible and relevant information. CONCLUSIONS: The current data
      support a collaborative model of treatment decision making for youth depression
      which: (1) focuses on the decision-making processes rather than who actually
      makes the decision; (2) is flexible to the individual needs and characteristics
      of the client; and (3) where caregiver involvement is optional. Shared decision
      making interventions and the use of decision aids should be considered for this
      area.

PMID- 24330308
TI  - Bendamustine in combination with high-dose radiotherapy and thalidomide is
      effective in treatment of multiple myeloma with central nervous system
      involvement.

PMID- 24330309
TI  - The degree of whey hydrolysis does not uniformly affect in vitro basophil and T
      cell responses of cow's milk-allergic patients.
AB  - BACKGROUND: Several studies investigated whether hydrolysed proteins can induce
      tolerance to cow's milk (CM) in children at risk of developing CM allergy. Due to
      methodological problems and inconsistent findings, the evidence for a tolerogenic
      effect is limited. A major problem is that different hydrolysates may give
      different outcomes due to variations in their production and composition.
      OBJECTIVE: The aim of the study was to investigate the effect of the degree of
      hydrolysis on the allergenicity and immunogenicity of whey hydrolysates. METHODS:
      The hydrolysis of whey was stopped at different time-points between 1 and 60 min.
      In 18 CM allergic patients, the allergenicity of the hydrolysates was determined
      by immunoblot and the basophil activation test. To test immunogenicity, CM
      specific T cell lines were generated. RESULTS: In most patients, increasing time
      of hydrolysis decreased IgE recognition and basophil activation. However, in five
      patients, hydrolysed proteins induced more basophil activation than non
      hydrolysed proteins. The immunoblot data indicated that these patients recognized
      either a 25- to 30-kDa degradation product of casein or a 10-kDa degradation
      product of whey. Although T cell activation was decreased in all patients over
      time, half of them still showed a positive response to the proteins after 60 min
      of hydrolysis. CONCLUSION: Increasing the time of hydrolysis reduces both
      allergenicity and immunogenicity of whey hydrolysates in most but not all
      patients. This indicates that not the degree of hydrolysis is decisive but the
      presence and stability of IgE and T cell epitopes in the hydrolysate recognized
      by individual patients.

PMID- 24330310
TI  - Maropitant prevented vomiting but not gastroesophageal reflux in anesthetized
      dogs premedicated with acepromazine-hydromorphone.
AB  - OBJECTIVE: To evaluate the efficacy of maropitant for prevention of vomiting and
      gastroesophageal reflux (GER) in dogs following acepromazine-hydromorphone
      premedication and inhalation anesthesia. STUDY DESIGN: Randomized, blinded,
      prospective clinical study. ANIMALS: Twenty-six dogs admitted for elective soft
      tissue or orthopedic procedures that were 3.1 +/-3.1 years of age and weighed
      20.5 +/- 11.4 kg. METHODS: Dogs were randomly assigned to one of two groups:
      Group M received maropitant (1.0 mg kg(-1) ) and Group S received 0.9% saline
      (0.1 mL kg(-1) ) intravenously 45-60 minutes before premedication with
      hydromorphone (0.1 mg kg(-1) ) and acepromazine (0.03 mg kg(-1) )
      intramuscularly. An observer blinded to treatment documented any retching or
      vomiting for 20 minutes before induction with propofol (2-6 mg kg(-1) ) and
      inhalation anesthesia. A pH probe inserted into the distal esophagus was used to
      detect GER. RESULTS: None of the dogs in Group M retched or vomited (0/13), 6/13
      (46%) in Group S were observed to retch or vomit, and the difference between
      groups was significant (p = 0.015). There were no differences between groups in
      the number of dogs with GER (Group M: 4/13, Group S: 6/13 dogs) or the number of
      reflux events. Esophageal pH at the end of anesthesia was significantly lower in
      both M and S groups in dogs with GER versus dogs without GER (p = 0.004 and
      0.011, respectively). Only dogs with GER in Group S had significantly lower pH at
      the end compared to the beginning of anesthesia (p = 0.004). CONCLUSIONS AND
      CLINICAL RELEVANCE: Intravenous maropitant prevented retching and vomiting
      associated with acepromazine-hydromorphone premedication. Maropitant did not
      prevent the occurrence of GER. Fewer dogs in Group M developed GER but further
      study with a larger number of dogs is necessary to determine if there is a
      significant difference.

PMID- 24330311
TI  - Factors associated with HIV infection among children born to mothers on the
      prevention of mother to child transmission programme at Chitungwiza Hospital,
      Zimbabwe, 2008.
AB  - BACKGROUND: Zimbabwe is one of the five countries worst affected by the HIV/AIDS
      pandemic with HIV infection contributing increasingly to childhood morbidity and
      mortality. Among the children born to HIV positive mothers participating in the
      PMTCT programme, 25% tested positive to HIV. We investigated factors associated
      with HIV infection among children born to mothers on the PMTCT programme.
      METHODS: A 1:1 unmatched case-control study was conducted at Chitungwiza
      Hospital, Zimbabwe, 2008. A case was defined as a child who tested HIV positive,
      born to a mother who had been on PMTCT programme. A control was a HIV negative
      child born to a mother who had been on PMTCT programme. An interviewer
      administered questionnaire was used to collect data on demographic
      characteristics, risk factors associated with HIV infection and immunization
      status. RESULTS: A total of 120 mothers were interviewed. Independent risk
      factors associated with HIV infection among children included maternal CD4 count
      of less than 200 during pregnancy [aOR = 7.1, 95% CI (2.6-17)], mixed feeding
      [aOR = 29, 95% CI (4.2-208)], being hospitalized since birth [aOR = 2.9, 95% CI
      (1.2-4.8)] whilst being exclusively breast fed for less than 6 months [aOR = 0.1
      (95% CI 0.03-0.4)] was protective. CONCLUSIONS: HIV infection among children
      increased if the mother's CD4 count was <=200 cells/MUL and if the child was
      exposed to mixed feeding. Breastfeeding exclusively for less than six months was
      protective. We recommended exclusive breast feeding period for the first six
      months and stop breast feeding after 6 months if affordable, sustainable and
      safe.

PMID- 24330312
TI  - Marmal-aid--a database for Infinium HumanMethylation450.
AB  - BACKGROUND: DNA methylation is indispensible for normal human genome function.
      Currently there is an increasingly large number of DNA methylomic data being
      released in the public domain allowing for an opportunity to investigate the
      relationships between the DNA methylome, genome function, and human phenotypes.
      The Illumina450K is one of the most popular platforms for assessing DNA
      methylation with over 10,000 samples available in the public domain. However,
      accessing all this data requires downloading each individual experiment and due
      to inconsistent annotation, accessing the right data can be a challenge.
      DESCRIPTION: Here we introduce 'Marmal-aid', the first standardised database for
      DNA methylation (freely available at http://marmal-aid.org). In Marmal-aid, the
      majority of publicly available Illumina HumanMethylation450 data is incorporated
      into a single repository allowing for re-processing of data including
      normalisation and imputation of missing values. The database is accessible in two
      ways: (1) Using an R package to allow for incorporation into existing analysis
      pipelines which can then be easily queried to gain insight into the functionality
      of certain CpG sites. This is aimed at a bioinformatician with experience in R.
      (2) Using a graphical interface allowing general biologists to query a pre
      defined set of tissues (currently 15) providing a reference database of the
      methylation state in these tissues for the 450,000 CpG sites profiled by the
      Illumina HumanMethylation450. CONCLUSION: Marmal-aid is the largest publicly
      available Illumina HumanMethylation450 methylation database combining Illumina
      HumanMethylation450 data from a number of sources into a single location with a
      single common annotation format. This allows for automated extraction using the R
      package and inclusion into existing analysis pipelines. Marmal-aid also provides
      a easy to use GUI to visualise methylation data in user defined genomic regions
      for various reference tissues.

PMID- 24330313
TI  - The archaellum: a rotating type IV pilus.
AB  - Microbes have evolved sophisticated mechanisms of motility allowing them to
      respond to changing environmental conditions. While this cellular process is well
      characterized in bacteria, the mode and mechanisms of motility are poorly
      understood in archaea. This study examines the motility of individual cells of
      the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. Specifically, we
      investigated motility of cells producing exclusively the archaeal swimming
      organelle, the archaellum. Archaella are structurally and in sequence similar to
      bacterial type IV pili involved in surface motility via pilus extension
      retraction cycles and not to rotating bacterial flagella. Unexpectedly, our
      studies reveal a novel type of behaviour for type IV pilus like structures:
      archaella rotate and their rotation drives swimming motility. Moreover, we
      demonstrate that temperature has a direct effect on rotation velocity explaining
      temperature-dependent swimming velocity. 

PMID- 24330314
TI  - Rural health networks: adapting to a changing health care environment.

PMID- 24330315
TI  - Pigmentation and melanocyte supply to the epidermis depend on type XVII collagen.
AB  - Genetic deficiency of type XVII collagen (C17), laminin-332 or type VII collagen
      causes epidermolysis bullosa (EB). Spontaneous correction of the deficiency, also
      known as revertant mosaicism, is caused by a second somatic mutation that
      restores protein expression resulting in clinically healthy (revertant) patches
      surrounded by fragile (mutant) skin. Interestingly, in some patients, patches of
      revertant skin show hyperpigmentation. To study the possible role of affected
      proteins in pigmentation and melanocyte distribution, we investigated clinical
      documentation and skin biopsy specimens of 13 revertant EB patients having
      correcting mutations in the COL17A1, LAMB3 or COL7A1 genes. Analysis revealed
      that lack of C17 led to decreased melanin intensity and melanocyte density in the
      epidermis when compared with the revertant patches. Reversions of LAMB3 and
      COL7A1 in keratinocytes did not influence clinical pigmentation or density of
      melanocytes. We conclude that in human skin, melanocyte supply to the epidermis
      depends on C17 expression in keratinocytes. 

PMID- 24330316
TI  - Competition and facilitation in synthetic communities of arbuscular mycorrhizal
      fungi.
AB  - Interactions between arbuscular mycorrhizal fungal (AMF) species cocolonizing the
      same host plant are still little understood in spite of major ecological
      significance of mycorrhizal symbiosis and widespread occurrence of these fungi in
      communities rather than alone. Furthermore, shifting the composition of AMF
      communities has demonstrated consequences for the provision of symbiotic benefits
      to the host as well as for the qualities of ecosystem services. Therefore, here
      we addressed the nature and strength of interactions between three different AMF
      species in all possible two-species combinations on a gradient of inoculation
      densities. Fungal communities were established in pots with Medicago truncatula
      plants, and their composition was assessed with taxon-specific real-time PCR
      markers. Nature of interactions between the fungi was varying from competition to
      facilitation and was influenced by both the identity and relative abundance of
      the coinoculated fungi. Plants coinoculated with Claroideoglomus and Rhizophagus
      grew bigger and contained more phosphorus than with any of these two fungi
      separately, although these fungi obviously competed for root colonization. On the
      other hand, plants coinoculated with Gigaspora and Rhizophagus, which facilitated
      each other's root colonization, grew smaller than with any of these fungi
      separately. Our results point to as yet little understood complexity of
      interactions in plant-associated symbiotic fungal communities, which, depending
      on their composition, can induce significant changes in plant host growth and/or
      phosphorus acquisition in either direction.

PMID- 24330317
TI  - Kimura's disease with prurigo lesions treated with systemic indomethacin.

PMID- 24330318
TI  - Psychosocial supportive care services for haematopoietic stem cell transplant
      patients; a service evaluation of three UK transplant centres.
AB  - Following haematopoietic stem cell transplant (HSCT) some patients experience
      long-term physical and psychosocial problems which impact on everyday life. The
      aim of this service evaluation was to investigate the psychosocial supportive
      care available for HSCT patients in three UK centres, particularly related to
      five identified areas of concern: fatigue; psychological distress; vocational and
      financial issues; sexuality, and fertility. HSCT health professionals were
      invited to audio-recorded semi-structured interviews. Enquiry was made into
      supportive care provided routinely (proactive), provided in response to a need
      (reactive) and missing (gaps in service) from pre-transplant to 18 months post
      transplant. Information gathered was transcribed and subjected to framework
      analysis. Interviews were conducted with 84 staff including nurses, doctors,
      psychologists, social workers, physiotherapists, dieticians and occupational
      therapists. Support for the five main areas of concern was variable across
      centres particularly with limitation of services for psychology; sexual
      dysfunction and fertility. Pro-active interventions such as psychological
      screening were rare with support being more commonly provided in response to an
      identified need. Support provided reactively for the areas of concern was
      comprehensive across professional groups and centres. Further work explores
      patients' psychosocial issues and other ways of providing adjuvant support. 

PMID- 24330319
TI  - Fission yeast IQGAP maintains F-actin-independent localization of myosin-II in
      the contractile ring.
AB  - During cytokinesis in many eukaryotic cells, myosin-II concentrates at the
      equatorial cortex with actin filaments (F-actin) and is supposed to generate
      forces to divide the cell into two, which is called the contractile ring (CR)
      hypothesis. Several lines of evidence indicate that the myosin-II is recruited
      independently of F-actin and interacts specifically with the equatorial F-actin.
      Molecular details of these mechanisms are still unknown. We used the fission
      yeast Schizosaccharomyces pombe to investigate the regulation of myosin-II
      localization. We demonstrate that the CR myosin-II was composed of F-actin
      dependent and -independent fractions by simultaneously observing F-actin and
      myosin. The F-actin-independent fraction was visualized as cortical dots in the
      absence of F-actin. IQGAP Rng2, an indispensable element of CR, was implicated in
      maintenance of the F-actin-independent fraction of myosin-II, whereas anillin
      Mid1 was required for assembly but not for maintenance of the fraction. In the CR
      of the rng2 mutant, myosin-II was less concentrated, unstable, and
      nonhomogeneous, which often resulted in cytokinesis failure. These results
      suggest that Rng2 tethers myosin-II to the cortex along the CR independently of F
      actin to provide a sufficient concentration. The robust localization of myosin-II
      would ensure successful cytokinesis.

PMID- 24330320
TI  - Impact of peer-led group education on the quality of life in patients with
      ankylosing spondylitis.
AB  - OBJECTIVES: To determine the effect of peer-led group education on the quality of
      life and depression in patients with ankylosing spondylitis (AS). METHODS: Eighty
      patients with definite AS were allocated randomly to either the education or
      control group. The education group (n = 40) was subjected to a peer-led group
      education program about disease and was given an educational booklet, while the
      control group (n = 40) was given the educational booklet only. Levels of quality
      of life and depression were measured at baseline, immediately after education
      (fourth week) and at 6 months in both groups. RESULTS: The results are based on
      56 (n = 27, education group; n = 29, control group) patients. The level of
      quality of life and depressive symptoms were not changed except for a
      deterioration in the social functioning subgroup of Short From (SF)-36 in both
      groups. When the groups were compared, there were no significant differences
      between changes in social functioning scores. CONCLUSIONS: Peer-led education did
      not alter quality of life levels and depression scores. However, because of the
      maintainance of quality of life levels, this type of intervention may be
      considered as a supplementary intervention to the standard medical care for
      management of AS.

PMID- 24330322
TI  - Development of a surgical procedure for implantation of a prototype
      suprachoroidal retinal prosthesis.
AB  - BACKGROUND: Current surgical techniques for retinal prosthetic implantation
      require long and complicated surgery, which can increase the risk of
      complications and adverse outcomes. METHOD: The suprachoroidal position is known
      to be an easier location to access surgically, and so this study aimed to develop
      a surgical procedure for implanting a prototype suprachoroidal retinal
      prosthesis. The array implantation procedure was developed in 14 enucleated eyes.
      A full-thickness scleral incision was made parallel to the intermuscular septum
      and superotemporal to the lateral rectus muscle. A pocket was created in the
      suprachoroidal space, and the moulded electrode array was inserted. The scleral
      incision was closed and scleral anchor point sutured. In 9 of the 14 eyes
      examined, the device insertion was obstructed by the posterior ciliary
      neurovascular bundle. Subsequently, the position of this neurovascular bundle in
      10 eyes was characterized. Implantation and lead routing procedure was then
      developed in six human cadavers. The array was tunnelled forward from behind the
      pinna to the orbit. Next, a lateral canthotomy was made. Lead fixation was
      established by creating an orbitotomy drilled in the frontal process of the
      zygomatic bone. The lateral rectus muscle was detached, and implantation was
      carried out. Finally, pinna to lateral canthus measurements were taken on 61
      patients in order to determine optimal lead length. RESULTS: These results
      identified potential anatomical obstructions and informed the anatomical fitting
      of the suprachoroidal retinal prosthesis. CONCLUSION: As a result of this work, a
      straightforward surgical approach for accurate anatomical suprachoroidal array
      and lead placement was developed for clinical application.

PMID- 24330321
TI  - Metabolic syndrome in bipolar disorder and schizophrenia: dietary and lifestyle
      factors compared to the general population.
AB  - OBJECTIVE: Since a poor diet is often cited as a contributor to metabolic
      syndrome for subjects diagnosed with bipolar disorder and schizophrenia, we
      sought to examine dietary intake, cigarette smoking, and physical activity in
      these populations and compare them with those for the general population.
      METHODS: Individuals diagnosed with bipolar disorder (n = 116) and schizophrenia
      (n = 143) were assessed for dietary intake, lifestyle habits, and metabolic
      syndrome and compared to age-, gender-, and race-matched subjects from the
      National Health and Nutrition Examination Survey (NHANES) 1999-2000.
      Additionally, matched subgroups within the patient populations were compared to
      elicit any differences. RESULTS: As expected, the metabolic syndrome rate was
      higher in the samples with bipolar disorder (33%) and schizophrenia (47%)
      compared to matched NHANES controls (17% and 11%, respectively), and not
      different between the patient groups. Surprisingly, both subjects with bipolar
      disorder and those with schizophrenia consumed fewer total calories,
      carbohydrates and fats, as well as more fiber (p < 0.03), compared to NHANES
      controls. No dietary or activity differences between patient participants with
      and without metabolic syndrome were found. Subjects with schizophrenia had
      significantly lower total and low-density cholesterol levels (p < 0.0001)
      compared to NHANES controls. Subjects with bipolar disorder smoked less (p =
      0.001), exercised more (p = 0.004), and had lower body mass indexes (p = 0.009)
      compared to subjects with schizophrenia. CONCLUSIONS: Counter to predictions, few
      dietary differences could be discerned between schizophrenia, bipolar disorder,
      and NHANES control groups. The subjects with bipolar disorder exhibited healthier
      behaviors than the patients with schizophrenia. Additional research regarding
      metabolic syndrome mechanisms, focusing on non-dietary contributions, is needed.

PMID- 24330323
TI  - Can adding a standardized observational tool to interdisciplinary evaluation
      enhance the detection of pain in older adults with cognitive impairments?
AB  - OBJECTIVE: The prevalence of chronic pain ranges from 40% to 80% in long-term
      care facilities, and it is especially high among older adults who are unable to
      communicate due to cognitive impairments. Although validated assessment tools
      exist, pain detection in this population is often done by interdisciplinary
      evaluation (IE), which largely relies on the subjective impression of health care
      providers. The aim of this study was to examine the agreement between the IE and
      validated observational pain tools. SETTING: We recruited 59 residents with
      limited ability to communicate. The pain behaviors of each participant were
      assessed with two validated tools, the Pain Assessment Checklist for Seniors with
      Limited Ability to Communicate (PACSLAC) and the Pain Assessment in Advanced
      Dementia (PAINAD), during transfer or mobilization. The results were then
      compared with the findings of the IE. RESULTS: The correlation between the
      PACSLAC and PAINAD was high (r = 0.79 [95% CI: 0.67-0.87]). However, we found a
      low to moderate association between the PACSLAC and the IE (r = 0.34 [95% CI:
      0.09-0.55]), and a weaker association was observed between the PAINAD and the IE
      (r = 0.25 [95% CI: -0.02-0.48]). When the IE concluded that there was an absence
      of pain behavior, the PAINAD and the PACSLAC detected the presence of pain in
      13.6% and 27.1% of the cases respectively. CONCLUSION: These results may be
      explained by an inability of IE to assess pain correctly or by instruments
      providing false positive results. Nevertheless, as detection of pain is difficult
      in this population, our research supports the use of validated tools to
      complement assessment of pain by the IE and make sure that no pain goes
      undetected.

PMID- 24330324
TI  - Primary lysis of eosinophils in severe desquamative asthma.
AB  - Primary lysis of eosinophils liberates free eosinophil granules (FEGs) releasing
      toxic proteins in association with bronchial epithelial injury repair. Eosinophil
      lysis may be significantly pathogenic. Bronchial mucosal FEGs are associated with
      uncontrolled asthma, severe asthma, aspirin-sensitive asthma, and lethal asthma.
      FEGs in the bronchial wall may characterize severe asthma without sputum
      eosinophilia. Excessive numbers of sputum FEGs occur in severe exacerbations of
      asthma and are reduced along with clinical improvement. Occurrence of FEGs
      affects interpretation of other sputum biomarkers including numbers of
      eosinophils, ECP, and eosinophil-stained macrophages. Thus, eosinophil lysis
      produces FEGs as bronchial biomarkers of severe asthma. Blood eosinophils in
      severe asthma seem primed exhibiting a propensity to lyse that is greater the
      more severe the asthma. Proclivity of blood eosinophils to lyse also
      distinguished three levels of severity among children with exacerbations of
      asthma. Numerous FEGs releasing toxic proteins occur in association with grave
      derangement and shedding of epithelium in severe asthma. Subepithelial FEGs
      correlate negatively with intact bronchial epithelium in clinically uncontrolled
      asthma. Significant correlations between sputum ECP, Creola bodies, and severity
      of asthma exacerbations have also been demonstrated. Hence, eosinophil lysis
      apparently causes epithelial desquamation in severe asthma. Exaggerated
      epithelial repair in turn would contribute to inflammatory and remodelling
      features of severe asthma. Perseverance of FEGs together with maintained disease
      activity, despite treatment with 'eosinophil-depleting' steroids and anti-IL5
      biologicals, agrees with the possibility that eosinophil lysis is worthy target
      for novel anti-asthma drugs. Priming and lysis of eosinophils, and protein
      release from FEGs, are regulated and can be targeted. Eosinophil lysis and FEGs
      belong to the disease picture of severe asthma and need consideration in asthma
      studies concerned with phenotypes, biomarkers, roles of epithelial injury/repair,
      and targeting novel drugs. 

PMID- 24330326
TI  - Clinical investigation of the effect of calcium hydroxide intracanal dressing on
      bacterial lipopolysaccharide reduction from infected root canals.
AB  - The purpose of this clinical study was to determine the effect of 7 day
      intracanal dressing with calcium hydroxide on the amount of bacterial
      lipopolysaccharide (LPS; endotoxin) in human teeth with necrotic and infected
      pulp and apical periodontitis. Twenty-five single-rooted teeth with necrotic
      pulps and apical periodontitis were selected. Samples were collected before (S1),
      after root canal preparation (S2) and after 7 day intracanal dressing with
      calcium hydroxide (S3). The limulus amoebocyte lysate assay was used to quantify
      LPS. LPS was present in 100% of the root canals before (S1), after preparation
      (S2) and after 7 day intracanal dressing (S3). A significant reduction, equal to
      29.54%, was found after root canal preparation (P < 0.05). A significant
      difference (equal to 25.26% reduction) was also detected between S2 and S3 (P <
      0.05). Total endotoxin reduction (S3 compared with S1) was found to be 47.34%.
      Endotoxin concentration of the infected root canals was reduced after root canal
      preparation and also after 7 days of dressing of canals with calcium hydroxide;
      however, relatively high values of endotoxin remained in the root canals.

PMID- 24330325
TI  - The cost-effectiveness and consumer acceptability of taxation strategies to
      reduce rates of overweight and obesity among children in Australia: study
      protocol.
AB  - BACKGROUND: Childhood obesity is a recognised public health problem and around
      25% of Australian children are overweight or obese. A major contributor is the
      obesogenic environment which encourages over consumption of energy dense nutrient
      poor food. Taxation is commonly proposed as a mechanism to reduce consumption of
      poor food choices and hence reduce rates of obesity and overweight in the
      community. METHODS/DESIGN: An economic model will be developed to assess the
      lifetime benefits and costs to a cohort of Australian children by reducing energy
      dense nutrient poor food consumption through taxation mechanisms. The model
      inputs will be derived from a series of smaller studies. Food options for
      taxation will be derived from literature and expert opinion, the acceptability
      and impact of price changes will be explored through a Citizen's Jury and a
      discrete choice experiment and price elasticities will be derived from the
      discrete choice experiment and consumption data. DISCUSSION: The health care
      costs of managing rising levels of obesity are a challenge for all governments.
      This study will provide a unique contribution to the international knowledge base
      by engaging a variety of robust research techniques, with a multidisciplinary
      focus and be responsive to consumers from diverse socio-economic backgrounds.

PMID- 24330327
TI  - Field performance of transgenic sugarcane produced using Agrobacterium and
      biolistics methods.
AB  - Future genetic improvement of sugarcane depends, in part, on the ability to
      produce high-yielding transgenic cultivars with improved traits such as herbicide
      and insect resistance. Here, transgenic sugarcane plants generated by different
      transformation methods were assessed for field performance over 3 years.
      Agrobacterium-mediated (Agro) transgenic events (35) were produced using four
      different Agrobacterium tumefaciens strains, while biolistic (Biol) transgenic
      events (48) were produced using either minimal linearized DNA (LDNA) transgene
      cassettes with 5', 3' or blunt ends or whole circular plasmid (PDNA) vectors
      containing the same transgenes. A combined analysis showed a reduction in growth
      and cane yield in Biol, Agro as well as untransformed tissue culture (TC) events,
      compared with the parent clone (PC) Q117 (no transformation or tissue culture) in
      the plant, first ratoon and second ratoon crops. However, when individual events
      were analysed separately, yields of some transgenic events from both Agro and
      Biol were comparable to PC, suggesting that either transformation method can
      produce commercially suitable clones. Interestingly, a greater percentage of Biol
      transformants were similar to PC for growth and yield than Agro clones. Crop
      ratoonability and sugar yield components (Brix%, Pol%, and commercial cane sugar
      (CCS)) were unaffected by transformation or tissue culture. Transgene expression
      remained stable over different crop cycles and increased with plant maturity.
      Transgene copy number did not influence transgene expression, and both
      transformation methods produced low transgene copy number events. No consistent
      pattern of genetic changes was detected in the test population using three DNA
      fingerprinting techniques. 

PMID- 24330328
TI  - Helicobacter pylori periplasmic receptor CeuE (HP1561) modulates its nickel
      affinity via organic metallophores.
AB  - In Gram-negative bacteria, nickel uptake is guaranteed by multiple and complex
      systems that operate at the membrane and periplasmic level. Helicobacter pylori
      employs other yet uncharacterized systems to import the nickel required for the
      maturation of key enzymes, such as urease and hydrogenase. H. pylori CeuE protein
      (HP1561), previously annotated as the periplasmic component of an ATP-binding
      cassette (ABC)-type transporter apparatus responsible of haem/siderophores or
      other Fe(III)-complexes uptake, has been recently proposed to be on the contrary
      involved in nickel/cobalt acquisition. In this work, the crystal structure of H.
      pylori CeuE has been determined at 1.65 A resolution using the single anomalous
      dispersion (SAD) method. It comprises two structurally similar globular domains,
      each consisting of a central five-stranded beta-sheet surrounded by alpha
      helices, an arrangement commonly classified as a Rossmann-like fold.
      Structurally, H. pylori CeuE belongs to the class III periplasmic substrate
      binding protein. Both crystallographic data and fluorescence binding assays allow
      to exclude a role of the protein in the transport of Vitamin B12, enterobactin,
      haem and isolated Ni(2+) ions. On the contrary, the crystal structure and plasmon
      resonance studies about CeuE/Ni-(l-His)2 complex indicate that in H. pylori
      nickel transport is supported by CeuE protein and requires the presence of a
      natural nickelophore, analogously to what has been recently demonstrated for NikA
      from Escherichia coli.

PMID- 24330329
TI  - A call to arms: on refining Plasmodium vivax microsatellite marker panels for
      comparing global diversity.
AB  - BACKGROUND: Microsatellite (MS) markers have become an important tool for
      studying the population diversity, evolutionary history and multiplicity of
      infection (MOI) of malaria parasite infections. MS are typically selected on the
      basis of being highly polymorphic. However, it is known that the polymorphic
      potential (mutability) of each marker can vary as much as two orders of
      magnitude, which radically changes how diversity is represented in the genome
      from one marker to the next. Over the past decade, approximately 240 Plasmodium
      vivax MS have been published, comprising nine major panels of markers.
      Inconsistent usage of each panel has resulted in a surfeit of descriptive genetic
      diversity data that are largely incomparable between populations. The objective
      of this study was to statistically evaluate the quality of individual MS markers
      in order to validate a refined panel of markers that will provide a balanced
      picture of P. vivax population diversity. METHODS: All previously published data,
      including genetic diversity indices, MS parameters, and population parameters,
      were assembled from 18 different global studies into a flat file to facilitate
      statistical analysis and modelling using JMP(r) Genomics 6.0 (SAS Institute Inc,
      Cary, NC, USA). Statistical modeling was employed to down-select markers with
      extreme variation among the mean number of alleles, expected heterozygosity,
      maximum repeat length and/or chromosomal location of the repeat. Individual MS
      were analysed by step-down whole model linear regression and standard least
      squares fit models, both stratified by annual parasite incidence to identify MS
      markers with values significantly different from the mean. RESULTS: Of the 42 MS
      under evaluation in this study, 18 (nine high priority) were identified as ideal
      candidates for measuring population diversity between global regions, while five
      (two high priority) additional markers were identified as candidates for MOI
      studies. CONCLUSIONS: MS diversity was found to be a function of endemicity and
      motif structure. Evaluation of individual MS permitted the assembly of a refined
      panel of markers that can be reliably utilized in the field to compare population
      structures between global regions.

PMID- 24330330
TI  - The distribution of cerebral microbleeds determines their association with
      arterial stiffness in non-cardioembolic acute stroke patients.
AB  - BACKGROUND AND PURPOSE: Increased arterial stiffness causes vessel damage in the
      end-organs. Therefore small vessels in the brain may be susceptible to increased
      arterial stiffness. Cerebral microbleeds (CMBs) are topographically or
      pathophysiologically categorized as deep or infratentorial type and strictly
      lobar type. Whether the presence and location of CMBs are associated with
      brachial-ankle pulse wave velocity (baPWV) which represents a measure of arterial
      stiffness was investigated. METHODS: Between June 2006 and January 2012, 1137
      consecutive patients diagnosed with non-cardioembolic acute ischaemic stroke and
      who underwent baPWV measurement and brain gradient-echo imaging were enrolled.
      CMBs were classified as deep or infratentorial or strictly lobar according to
      their location. Severity of leukoaraiosis was determined using the Fazekas
      scoring system. RESULTS: CMBs were found in 30.7% of the included patients. These
      patients were older than those without CMBs. Mean baPWV was higher in patients
      with CMBs than in those without (20 +/- 5 m/s vs. 19 +/- 5 m/s; P = 0.001). When
      comparing baPWV according to the location of the CMB, it was higher in the deep
      or infratentorial CMB group than in the strictly lobar CMB group (22 +/- 5 m/s
      vs. 20 +/- 5 m/s; P = 0.001). In univariate and multivariate multinomial logistic
      regression analyses, baPWV was found to be independently associated with deep or
      infratentorial CMBs. CONCLUSIONS: Arterial stiffness was independently associated
      with deep or infratentorial CMBs but not lobar CMBs. These findings suggest a
      pathophysiological association between arterial stiffness and CMBs in the deep or
      infratentorial region.

PMID- 24330331
TI  - Attention deficit/hyperactivity disorders with co-existing substance use disorder
      is characterized by early antisocial behaviour and poor cognitive skills.
AB  - BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is associated with an
      increased risk of co-existing substance abuse. The Swedish legislation on
      compulsory healthcare can be applied to persons with severe substance abuse who
      can be treated involuntarily during a period of six months. This context enables
      a reliable clinical assessment of ADHD in individuals with severe substance use
      disorder (SUD). METHODS: In the context of compulsory care for individuals with
      severe SUD, male patients were assessed for ADHD, co-morbid psychiatric symptoms,
      psychosocial background, treatment history, and cognition. The data from the
      ADHD/SUD group (n = 60) was compared with data from (1) a group of individuals
      with severe substance abuse without known ADHD (SUD group, n = 120), as well as
      (2) a group with ADHD from an outpatient psychiatric clinic (ADHD/Psych group, n
      = 107). RESULTS: Compared to the general SUD group in compulsory care, the
      ADHD/SUD group had already been significantly more often in compulsory care
      during childhood or adolescence, as well as imprisoned more often as adults. The
      most common preferred abused substance in the ADHD/SUD group was stimulant drugs,
      while alcohol and benzodiazepine abuse was more usual in the general SUD group.
      Compared to the ADHD/Psych group, the ADHD/SUD group reported more ADHD symptoms
      during childhood and performed poorer on all tests of general intellectual
      ability and executive functions. CONCLUSIONS: The clinical characteristics of the
      ADHD/SUD group differed from those of both the SUD group and the ADHD/Psych group
      in several respects, indicating that ADHD in combination with SUD is a
      particularly disabling condition. The combination of severe substance abuse, poor
      general cognitive ability, severe psychosocial problems, including indications of
      antisocial behaviour, and other co-existing psychiatric conditions should be
      considered in treatment planning for adults with ADHD and SUD.

PMID- 24330332
TI  - Gene set bagging for estimating the probability a statistically significant
      result will replicate.
AB  - BACKGROUND: Significance analysis plays a major role in identifying and ranking
      genes, transcription factor binding sites, DNA methylation regions, and other
      high-throughput features associated with illness. We propose a new approach,
      called gene set bagging, for measuring the probability that a gene set replicates
      in future studies. Gene set bagging involves resampling the original high
      throughput data, performing gene-set analysis on the resampled data, and
      confirming that biological categories replicate in the bagged samples. RESULTS:
      Using both simulated and publicly-available genomics data, we demonstrate that
      significant categories in a gene set enrichment analysis may be unstable when
      subjected to resampling. We show our method estimates the replication probability
      (R), the probability that a gene set will replicate as a significant result in
      future studies, and show in simulations that this method reflects replication
      better than each set's p-value. CONCLUSIONS: Our results suggest that gene lists
      based on p-values are not necessarily stable, and therefore additional steps like
      gene set bagging may improve biological inference on gene sets.

PMID- 24330333
TI  - The carotid plaque imaging in acute stroke (CAPIAS) study: protocol and initial
      baseline data.
AB  - BACKGROUND: In up to 30% of patients with ischemic stroke no definite etiology
      can be established. A significant proportion of cryptogenic stroke cases may be
      due to non-stenosing atherosclerotic plaques or low grade carotid artery stenosis
      not fulfilling common criteria for atherothrombotic stroke. The aim of the CAPIAS
      study is to determine the frequency, characteristics, clinical and radiological
      long-term consequences of ipsilateral complicated American Heart Association
      lesion type VI (AHA-LT VI) carotid artery plaques in patients with cryptogenic
      stroke. METHODS/DESIGN: 300 patients (age >49 years) with unilateral DWI-positive
      lesions in the anterior circulation and non- or moderately stenosing (<70%
      NASCET) internal carotid artery plaques will be enrolled in the prospective
      multicenter study CAPIAS. Carotid plaque characteristics will be determined by
      high-resolution black-blood carotid MRI at baseline and 12 month follow up.
      Primary outcome is the prevalence of complicated AHA-LT VI plaques in cryptogenic
      stroke patients ipsilateral to the ischemic stroke compared to the contralateral
      side and to patients with defined stroke etiology. Secondary outcomes include the
      association of AHA-LT VI plaques with the recurrence rates of ischemic events up
      to 36 months, rates of new ischemic lesions on cerebral MRI (including clinically
      silent lesions) after 12 months and the influence of specific AHA-LT VI plaque
      features on the progression of atherosclerotic disease burden, on specific
      infarct patterns, biomarkers and aortic arch plaques. DISCUSSION: CAPIAS will
      provide important insights into the role of non-stenosing carotid artery plaques
      in cryptogenic stroke. The results might have implications for our understanding
      of stroke mechanism, offer new diagnostic options and provide the basis for the
      planning of targeted interventional studies. TRIAL REGISTRATION: NCT01284933.

PMID- 24330334
TI  - Coping strategies for activities of daily living in women whose hands affected by
      systemic sclerosis.
AB  - AIMS AND OBJECTIVES: To determine the challenges experienced by women with
      systemic sclerosis, whose hands affected, while performing activities of daily
      living and their coping strategies. BACKGROUND: Many of the patients with
      systemic sclerosis experience difficulties in performing daily activities. One of
      the most important reasons for that is the impaired hand function due to their
      diseases. DESIGN: A descriptive cross-sectional design was conducted and
      questionnaire was used in this study. METHODS: The study was performed in a
      Rheumatology Department at a tertiary-care hospital in Turkey between April 2010
      December 2011. Nineteen patients with systemic sclerosis with hand involvement
      were enrolled in this study. The data were collected by using both a demographic
      data form and an Evaluation of Daily Activity Questionnaire. RESULTS: According
      to Evaluation of Daily Activity Questionnaire, the most scored dimension that
      patients can do with much difficulty was 'eating' and the dimension that patients
      unable to do was 'washing/clothes care'. In 'eating' dimension, the most
      difficult activities were 'opening glass jar', 'opening juice bottle' and
      'opening bottle' that requiring the movement of rotation. Their coping strategies
      for these activities were as follows: try to open with a towel, try to remove the
      edge of the palm with a knife, use the hand palm and help from someone else
      (spouse, neighbour, etc.). In 'washing/clothes care' dimension, the most
      difficult activities were 'turning up hem of a skirt', 'washing up in bowl' and
      'cutting out material'. For these activities, they use some coping strategies
      such as getting help from tailor, washing in the machine instead of hand washing.
      CONCLUSION: This study demonstrates that impaired hand function affects the daily
      life activities of patients with systemic sclerosis, and patients have developed
      some coping strategies to overcome these difficulties. RELEVANCE TO CLINICAL
      PRACTICE: The coping strategies used by patients can be helpful for the other
      patients with systemic sclerosis.

PMID- 24330335
TI  - The functional relevance of polyploidization in the skin.
AB  - Cell proliferation and differentiation are tightly coupled through the regulation
      of the cell division cycle. To preserve specific functional properties in
      differentiated cells, distinct variants of the basic mitotic cell cycle are used
      in various mammalian tissues, leading to the formation of polyploid cells. In
      this issue of Experimental Dermatology, Gandarillas and Freije discuss the
      evidences for polyploidization in keratinocytes, a process whose physiological
      relevance is now becoming evident. A better evaluation of these unconventional
      cell cycles is required not only to improve our understanding of the development
      and structure of the epidermis but also for future therapies against skin
      diseases. 

PMID- 24330336
TI  - Mitigating prolonged QT interval in cancer nanodrug development for accelerated
      clinical translation.
AB  - BACKGROUND: Cardiac toxicity is the foremost reason for drug discontinuation from
      development to clinical evaluation and post market surveillance [Fung 35:293-317,
      2001; Piccini 158:317-326 2009]. The Food and Drug Administration (FDA) has
      rejected many potential pharmaceutical agents due to QT prolongation effects.
      Since drug development and FDA approval takes an enormous amount of time, money
      and effort with high failure rates, there is an increased focus on rescuing drugs
      that cause QT prolongation. If these otherwise safe and potent drugs were
      formulated in a unique way so as to mitigate the QT prolongation associated with
      them, these potent drugs may get FDA approval for clinical use. Rescuing these
      compounds not only benefit the patients who need them but also require much less
      time and money thus leading to faster clinical translation. In this study, we
      chose curcumin as our drug of choice since it has been shown to posses anti-tumor
      properties against various cancers with limited toxicity. The major limitations
      with this pharmacologically active drug are (a) its ability to prolong QT by
      inhibiting the hERG channel and (b) its low bioavailability. In our previous
      studies, we found that lipids have protective actions against hERG channel
      inhibition and therefore QT prolongation. RESULTS: Results of the manual patch
      clamp assay of HEK 293 cells clearly illustrated that our hybrid nanocurcumin
      formulation prevented the curcumin induced inhibition of hERG K+ channel at
      concentrations higher than the therapeutic concentrations of curcumin. Comparing
      the percent inhibition, the hybrid nanocurcumin limited inhibition to 24.8% at a
      high curcumin equivalent concentration of 18 MUM. Liposomal curcumin could only
      decrease this inhibition upto 30% only at lower curcumin concentration of 6 MUM
      but not at 18 MUM concentration. CONCLUSIONS: Here we show a curcumin
      encapsulated lipopolymeric hybrid nanoparticle formulation which could protect
      against QT prolongation and also render increased bioavailability and stability
      thereby overcoming the limitations associated with curcumin.

PMID- 24330338
TI  - Population of ATP synthase molecules in mitochondria is limited by available 6.8
      kDa proteolipid protein (MLQ).
AB  - A 6.8-kDa proteolipid (called MLQ) is a hydrophobic mitochondrial protein with
      unknown function that is loosely associated with ATP synthase. Here, we show that
      MLQ-knockdown HeLa cells lose population of ATP synthase in mitochondria. This is
      not due to low transcription of subunit genes of ATP synthase because levels of
      mRNA for alpha- and beta-subunits are unaffected by the knockdown. As a
      consequence, the knockdown cells show low mitochondrial ATP synthesis activity,
      grow slowly in the normal medium, and are vulnerable to glucose deprivation.
      Given that the expression of MLQ varies responding to cellular conditions, MLQ is
      a potential regulator of the mitochondrial ATP synthesis.

PMID- 24330337
TI  - Partial characterization, antioxidative properties and hypolipidemic effects of
      oilseed cake of Allanblackia floribunda and Jatropha curcas.
AB  - BACKGROUND: High fat diet is known to induce oxidative stress and abnormal
      changes in lipid metabolism. Many traditional plants have been shown to possess
      antioxidant and lipid-lowering activities, improving on oxidative status and
      lipid profile. In this paper, we characterized and examined the antioxidative
      properties of the oilseed cake of A. floribunda and J. curcas. We also evaluated
      their effect on lipid profile in the plasma and liver of experimental rats placed
      on a high fat diet. METHODS: For a partial characterization, the qualitative and
      quantitative analyses of storage proteins, dietary fibre and polyphenol content
      were evaluated. Four extracts (aqueous, ethanolic, methanolic and 0.1 N HCl) were
      evaluated for their antioxidant properties and scavenging activities. The effect
      on lipid profile was evaluated after the administration of the crude extracts to
      albino rats placed on a high fat diet. RESULTS: Our results showed that J. curcas
      contains 10 times more storage proteins than A. floribunda while A. floribunda
      contains twice as much total dietary fibre than J. curcas. An evaluation of the
      different families of storage proteins showed that J. curcas has glutelins as the
      major storage proteins in its seeds (61.65 mg/g d.m), followed by globulins
      (25.30 mg/g d.m) and albumins (18.30 mg/g d.m). The electrophoretic analyses
      revealed a diversity of bands at the level of the different families and for both
      species. The evaluation of the in vitro antioxidant activities showed that A.
      floribunda extracts had higher antioxidant properties. Although the composition
      of A. floribunda and J. curcas oilseed cake are different, they lowered serum
      triglycerides (TG), total cholesterol (TC) and blood glucose level. CONCLUSION:
      These results show that the oilseed cake of A. floribunda and J. curcas possess
      antioxidant properties with an effect on blood glucose level and lipid profile.

PMID- 24330339
TI  - Erythema annulare centrifugum during rituximab treatment for autoimmune
      haemolytic anaemia.

PMID- 24330340
TI  - Assessment of the relationship between aortic stiffness and left ventricular
      functions with echocardiography in patients with Sjogren's syndrome.
AB  - BACKGROUND AND AIM: Capable of multi-organ involvement in Sjogren's syndrome
      (SS), cardiac findings of pulmonary effusion, left ventricular diastolic
      dysfunction and pulmonary hypertension are seen in patients with SS. Aortic
      stiffness (AS) reflects the mechanical tension and elasticity of the aorta. In
      this study, our aim is to determine if there is any differences in AS and left
      ventricular function between patients diagnosed as SS and healthy control groups.
      METHODS AND RESULTS: We enrolled 50 patients with SS and 47 healthy volunteers
      with similar demographic characteristics. It was found that isovolumetric
      relaxation time (IVRT) and deceleration time (DT) were significantly longer and
      early diastolic wave (E) was significantly lower in patients with SS, but there
      was no difference in the other parameters. When tissue Doppler echocardiography
      (TDE) findings were compared between the two groups, it was found that myocardial
      systolic wave (Sm), myocardial early diastolic wave (Em) and Em/Am ratio were
      significantly lower, and myocardial isovolumetric relaxation time (IVRTm) and
      myocardial performance index (MPI) values were significantly higher in patients
      with SS. A significant positive correlations between aortic strain and Sm (r =
      0.35, P < 0.001), Em (r = 0.42, P < 0.001) and Em/Am (r = 0.26, P = 0.008) and
      negative correlations in IVRTm (r = -0.36, P < 0.001) and MPI (r = -0.24, P =
      0.01) were detected. A significant positive correlation between aortic
      distensibility and Sm (r = 0.36, P < 0.001), Em (r = 0.44, P < 0.001), Em/Am (r =
      0.26, P = 0.009) and negative correlation of IVRTm (r = -0.22, P = 0.02) were
      determined. CONCLUSION: There is a significant relationship between AS and left
      ventricular diastolic dysfunction in patients with SS in this study. The
      parameters of aortic elasticity measured by 2D echocardiographic methods can be
      beneficial in predicting early cardiovascular risk in SS.

PMID- 24330341
TI  - Unusual presentation of late intraocular lens dislocation.

PMID- 24330342
TI  - Advancing biomarker research: utilizing 'Big Data' approaches for the
      characterization and prevention of bipolar disorder.
AB  - OBJECTIVE: To provide a strategic framework for the prevention of bipolar
      disorder (BD) that incorporates a 'Big Data' approach to risk assessment for BD.
      METHODS: Computerized databases (e.g., Pubmed, PsychInfo, and MedlinePlus) were
      used to access English-language articles published between 1966 and 2012 with the
      search terms bipolar disorder, prodrome, 'Big Data', and biomarkers cross
      referenced with genomics/genetics, transcriptomics, proteomics, metabolomics,
      inflammation, oxidative stress, neurotrophic factors, cytokines, cognition,
      neurocognition, and neuroimaging. Papers were selected from the initial search if
      the primary outcome(s) of interest was (were) categorized in any of the following
      domains: (i) 'omics' (e.g., genomics), (ii) molecular, (iii) neuroimaging, and
      (iv) neurocognitive. RESULTS: The current strategic approach to identifying
      individuals at risk for BD, with an emphasis on phenotypic information and family
      history, has insufficient predictive validity and is clinically inadequate. The
      heterogeneous clinical presentation of BD, as well as its pathoetiological
      complexity, suggests that it is unlikely that a single biomarker (or an exclusive
      biomarker approach) will sufficiently augment currently inadequate phenotypic
      centric prediction models. We propose a 'Big Data'- bioinformatics approach that
      integrates vast and complex phenotypic, anamnestic, behavioral, family, and
      personal 'omics' profiling. Bioinformatic processing approaches, utilizing cloud-
      and grid-enabled computing, are now capable of analyzing data on the order of
      tera-, peta-, and exabytes, providing hitherto unheard of opportunities to
      fundamentally revolutionize how psychiatric disorders are predicted, prevented,
      and treated. High-throughput networks dedicated to research on, and the treatment
      of, BD, integrating both adult and younger populations, will be essential to
      sufficiently enroll adequate samples of individuals across the neurodevelopmental
      trajectory in studies to enable the characterization and prevention of this
      heterogeneous disorder. CONCLUSIONS: Advances in bioinformatics using a 'Big
      Data' approach provide an opportunity for novel insights regarding the
      pathoetiology of BD. The coordinated integration of research centers, inclusive
      of mixed-age populations, is a promising strategic direction for advancing this
      line of neuropsychiatric research.

PMID- 24330343
TI  - A randomized, rater-blinded, crossover study of the effects of oxymorphone
      extended release, fed versus fasting, on cognitive performance as tested with
      CANTAB in opioid-tolerant subjects.
AB  - BACKGROUND: The maximum plasma concentration (Cmax ) of oxymorphone extended
      release (ER) 20 mg and 40 mg is approximately 50% higher in fed than in fasted
      subjects, with most of the difference in area-under-the-curve (AUC) occurring in
      the first 4 hours post-dose. Hence, the US FDA recommends in the approved
      labeling that oxymorphone ER is taken at least 1 hour before or 2 hours after
      eating. METHODS: In order to determine the potential impact on cognitive
      performance of the increased absorption of oxymorphone ER, fed versus fasting, we
      conducted a randomized, rater-blinded, crossover study in 30 opioid-tolerant
      subjects, using tests from the Cambridge Neuropsychological Test Automated
      Battery (CANTAB). The subjects randomly received 40 mg oxymorphone ER after a
      high-fat meal of approximately 1,010 kCal or after fasting for 8-12 hours, and
      were tested 1 hour and 3 hours post-dose. RESULTS: The CANTAB tests, Spatial
      Recognition Memory (SRM) and Spatial Working Memory (SWM), showed no
      statistically significant differences between the fed and fasting conditions.
      However, sustained attention, as measured by the Rapid Visual Information
      Processing (RVP) CANTAB test, showed a statistically significant interaction of
      fed versus fasting and post-dose time of testing (F[1,28] = 6.88, P = 0.01),
      suggesting that 40 mg oxymorphone ER after a high-fat meal versus fasting
      mitigates the learning effect in this particular cognition domain from 1 hour to
      3 hours post-dose. CONCLUSION: Oxymorphone 40 mg ER affected cognitive
      performance similarly within 3 hours post-dose, whether given on an empty stomach
      or after a high-fat meal, suggesting that the effect of food on plasma
      concentration may not be relevant in the medication's impact on cognition.

PMID- 24330345
TI  - The food industry is neither friend, nor foe, nor partner.

PMID- 24330346
TI  - oca2 Regulation of chromatophore differentiation and number is cell type specific
      in zebrafish.
AB  - We characterized a zebrafish mutant that displays defects in melanin synthesis
      and in the differentiation of melanophores and iridophores of the skin and
      retinal pigment epithelium. Positional cloning and candidate gene sequencing link
      this mutation to a 410-kb region on chromosome 6, containing the oculocutaneous
      albinism 2 (oca2) gene. Quantification of oca2 mutant melanophores shows a
      reduction in the number of differentiated melanophores compared with wildtype
      siblings. Consistent with the analysis of mouse Oca2-deficient melanocytes,
      zebrafish mutant melanophores have immature melanosomes which are partially
      rescued following treatment with vacuolar-type ATPase inhibitor/cytoplasmic pH
      modifier, bafilomycin A1. Melanophore-specific gene expression is detected at the
      correct time and in anticipated locations. While oca2 zebrafish display
      unpigmented gaps on the head region of mutants 3 days post-fertilization,
      melanoblast quantification indicates that oca2 mutants have the correct number of
      melanoblasts, suggesting a differentiation defect explains the reduced
      melanophore number. Unlike melanophores, which are reduced in number in oca2
      mutants, differentiated iridophores are present at significantly higher numbers.
      These data suggest distinct mechanisms for oca2 in establishing differentiated
      chromatophore number in developing zebrafish.

PMID- 24330347
TI  - Analysis of the psychological impact of a vascular risk factor intervention:
      results from a cluster randomized controlled trial in Australian general
      practice.
AB  - BACKGROUND: Screening for vascular disease, risk assessment and management are
      encouraged in general practice however there is limited evidence about the
      emotional impact on patients. The Health Improvement and Prevention Study
      evaluated the impact of a general practice-based vascular risk factor
      intervention on behavioural and physiological risk factors in 30 Australian
      practices. The primary aim of this analysis is to investigate the psychological
      impact of participating in the intervention arm of the trial. The secondary aim
      is to identify the mediating effects of changes in behavioural risk factors or
      BMI. METHODS: This study is an analysis of a secondary outcome from a cluster
      randomized controlled trial. Patients, aged 40-65 years, were randomly selected
      from practice records. Those with pre-existing cardiovascular disease were
      excluded. Socio-demographic details, behavioural risk factors and psychological
      distress were measured at baseline and 12 months. The Kessler Psychological
      Distress Score (K10) was the outcome measure for multi-level, multivariable
      analysis and a product-of-coefficient test to assess the mediating effects of
      behaviour change. RESULTS: Baseline data were available 384 participants in the
      intervention group and 315 in the control group. Twelve month data were available
      for 355 in the intervention group and 300 in the control group. The K10 score of
      patients in the intervention group (14.78, SD 5.74) was lower at 12 months
      compared to the control group (15.97, SD 6.30). K10 at 12 months was
      significantly associated with the score at baseline and being unable to work but
      not with age, gender, change in behavioural risk factors or change in BMI.
      CONCLUSIONS: The reduction of K10 in the intervention group demonstrates that a
      general practice based intervention to identify and manage vascular risk factors
      did not adversely impact on the psychological distress of the participants. The
      impact of the intervention on distress was not mediated by a change in the
      behavioural risk factors or BMI, suggesting that there must be other mediators
      that might explain the positive impact of the intervention on emotional
      wellbeing. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12607000423415.

PMID- 24330348
TI  - The first recombinant FVIII produced in human cells--an update on its clinical
      development programme.
AB  - The development of inhibitors and the need for frequent venous access for FVIII
      injection are major challenges in current haemophilia treatment. Presently
      available recombinant FVIII (rFVIII) products produced in hamster cell lines are
      associated with inhibitor formation in up to 32% of previously untreated
      patients. The new human cell line-derived recombinant human FVIII (Human-cl
      rhFVIII) protein is the first native, unmodified truly human rFVIII product
      produced in a human cell line without additive animal proteins. The aim of using
      a human cell line for the production of rFVIII is the avoidance of non-human
      epitopes on rFVIII, thereby potentially reducing the rate of inhibitor
      development, avoiding allergic reactions and allowing personalized prophylaxis
      with the chance of fewer infusions. Studies to date show that prophylaxis with
      Human-cl rhFVIII prevents 96% of bleeding events in adults with severe
      haemophilia A when compared to on-demand treatment. Available pharmacokinetic
      data with a mean half-life of 17.1 h allow personalized prophylaxis with the
      chance of fewer infusions. Studies in previously treated children and adults
      indicate that Human-cl rhFVIII is efficacious and safe in the prevention and
      treatment of bleeding episodes and that none of the treated patients developed
      inhibitors or allergic reactions thus far.

PMID- 24330350
TI  - Dockerin-containing protease inhibitor protects key cellulosomal cellulases from
      proteolysis in Clostridium cellulolyticum.
AB  - Cellulosomes are key for lignocellulosic biomass degradation in cellulolytic
      Clostridia. Better understanding of the mechanism of cellulosome regulation would
      allow us to improve lignocellulose hydrolysis. It is hypothesized that
      cellulosomal protease inhibitors would regulate cellulosome architecture and then
      lignocellulose hydrolysis. Here, a dockerin-containing protease inhibitor gene
      (dpi) in Clostridium cellulolyticum H10 was characterized by mutagenesis and
      physiological analyses. The dpi mutant had a decreased cell yield on glucose,
      cellulose and xylan, lower cellulose utilization efficiency, and a 70% and 52%
      decrease of the key cellulosomal components, Cel48F and Cel9E respectively. The
      decreased cellulolysis is caused by the proteolysis of major cellulosomal
      components, such as Cel48F and Cel9E. Disruption of cel9E severely impaired cell
      growth on cellulose while loss of cel48F completely abolished cellulolytic
      activity. These observations are due to the combinational results of gene
      inactivation and polar effects caused by intron insertion. Purified recombinant
      Dpi showed inhibitory activity against cysteine protease. Taken together, Dpi
      protects key cellulosomal cellulases from proteolysis in H10. This study
      identified the physiological importance of cellulosome-localized protease
      inhibitors in Clostridia. 

PMID- 24330349
TI  - An investigation into IgE-facilitated allergen recognition and presentation by
      human dendritic cells.
AB  - BACKGROUND: Allergen recognition by dendritic cells (DCs) is a key event in the
      allergic cascade leading to production of IgE antibodies. C-type lectins, such as
      the mannose receptor and DC-SIGN, were recently shown to play an important role
      in the uptake of the house dust mite glycoallergen Der p 1 by DCs. In addition to
      mannose receptor (MR) and DC-SIGN the high and low affinity IgE receptors, namely
      FcepsilonRI and FcepsilonRII (CD23), respectively, have been shown to be involved
      in allergen uptake and presentation by DCs. OBJECTIVES: This study aims at
      understanding the extent to which IgE- and IgG-facilitated Der p 1 uptake by DCs
      influence T cell polarisation and in particular potential bias in favour of Th2.
      We have addressed this issue by using two chimaeric monoclonal antibodies
      produced in our laboratory and directed against a previously defined epitope on
      Der p 1, namely human IgE 2C7 and IgG1 2C7. RESULTS: Flow cytometry was used to
      establish the expression patterns of IgE (FcepsilonRI and FcepsilonRII) and IgG
      (FcgammaRI) receptors in relation to MR on DCs. The impact of FcepsilonRI,
      FcepsilonRII, FcgammaRI and mannose receptor mediated allergen uptake on Th1/Th2
      cell differentiation was investigated using DC/T cell co-culture experiments.
      Myeloid DCs showed high levels of FcepsilonRI and FcgammaRI expression, but low
      levels of CD23 and MR, and this has therefore enabled us to assess the role of
      IgE and IgG-facilitated allergen presentation in T cell polarisation with minimal
      interference by CD23 and MR. Our data demonstrate that DCs that have taken up Der
      p 1 via surface IgE support a Th2 response. However, no such effect was
      demonstrable via surface IgG. CONCLUSIONS: IgE bound to its high affinity
      receptor plays an important role in Der p 1 uptake and processing by peripheral
      blood DCs and in Th2 polarisation of T cells.

PMID- 24330351
TI  - Evaluating a novel approach to enhancing dysphagia management: workplace-based,
      blended e-learning.
AB  - AIMS AND OBJECTIVES: To evaluate the learning effect and resource use cost of
      workplace-based, blended e-learning about dysphagia for stroke rehabilitation
      nurses. BACKGROUND: Dysphagia is a potentially life-threatening problem that
      compromises quality of life. In many countries, nurses play a crucial role in
      supporting the management of patients with swallowing problems, yet the
      literature reports a need for training. DESIGN: A single-group, pre- and post
      study with mixed methods. METHODS: Each blended e-learning session comprised a
      needs analysis, e-learning programmes, practical skills about modifying fluids
      and action planning to transfer learning into practice. Participants were the
      population of registered nurses (n = 22) and healthcare assistants (n = 10) on a
      stroke rehabilitation ward in a large, teaching hospital in England between
      August 2010-March 2011. Data collection comprised observation (34 hours),
      questionnaires administered at four time points to examine change in attitude,
      knowledge and practice, and estimating the resource use cost for the service.
      Nonparametric tests and content analysis were used to analyse the data. RESULTS:
      All participants achieved a nationally recognised level of competence. The
      learning effect was evident on the post- and follow-up measures, with some items
      of dysphagia knowledge and attitude achieving significance at the p <= 0.05
      level. The most common self-reported changes in practice related to medicines
      management, thickening fluids and oral hygiene. The resource use cost was
      estimated at L2688 for 108 hours training. CONCLUSIONS: Workplace-based, blended
      e-learning was an acceptable, cost effective way of delivering essential clinical
      knowledge and skills about dysphagia. RELEVANCE TO CLINICAL PRACTICE: Dysphagia
      should be viewed as a patient safety issue because of the risks of malnutrition,
      dehydration and aspiration pneumonia. As such, it is pertinent to many members of
      the interdisciplinary team. Consideration should be given to including dysphagia
      management in initial education and continuing professional development
      programmes.

PMID- 24330352
TI  - Evaluation of circumsporozoite protein of Plasmodium vivax to estimate its
      prevalence in the Republic of Korea: an observational study of incidence.
AB  - BACKGROUND: Plasmodium vivax re-emerged in 1993. Although the number of
      infections has been steadily decreasing, it is likely to continue to affect
      public health until it is eradicated. The aim of this study is to measure anti
      circumsporozoite protein (CSP) antibody and compare malaria prevalence. As to
      understand the prevalence, an epidemiology study has to be conducted in the
      Republic of Korea. METHODS: A total of 1,825 and 1,959 blood samples were
      collected in 2010 and 2011, respectively, from the inhabitants of Ganghwa and
      Cheorwon counties. The antibody titers of the inhabitants were measured by enzyme
      linked immunosorbent assay (ELISA) using recombinant protein purified from
      Escherichia coli transformed with a CSP gene-inserted pET-28a(+) expression
      vector. Microscopic examination was performed to identify malaria parasites.
      RESULTS: The annual parasite incidence (API) in Ganghwa decreased from 4.28 in
      2010 to 2.23 in 2011, and that in Cheorwon decreased from 1.88 in 2010 to 1.15 in
      2011. The antibody-positive CSP rate in these areas also decreased from 18.14%
      (331/1825) in 2010 to 15.36% (301/1959) in 2011. Pearson analysis showed a strong
      correlation between the API and the antibody-positive CSP rate in these areas (r
      = 1.000, P < 0.01). The intensity of the immune responses of the inhabitants of
      Cheorwon, as measured by the mean optical density, decreased from 0.9186 +/-
      0.0472 in 2010 to 0.7035 +/- 0.0457 in 2011 (P = 0.034), but increased in Ganghwa
      from 0.7649 +/- 0.0192 in 2010 to 0.8237 +/- 0.1970 in 2011 (P = 0.006). The
      immune response increased according to age (r = 0.686, P = 0.041). CONCLUSIONS:
      The positive CSP-ELISA rate was closely related to the API in the study areas.
      This suggests that seroepidemiological studies based on CSP-ELISA may be helpful
      in estimating the malaria prevalence. Moreover, such studies can be used to
      establish and evaluate malaria control and eradication programmes in high-risk
      areas in Korea.

PMID- 24330353
TI  - Notch-1 mediates endothelial cell activation and invasion in psoriasis.
AB  - Notch receptor-ligand interactions are critical for cell proliferation,
      differentiation and survival; however, the role of Notch signalling in psoriasis
      remains to be elucidated. Serum amyloid A (A-SAA) is an acute-phase protein with
      cytokine-like properties, regulates cell survival pathways and is implicated in
      many inflammatory conditions. To examine the role of Notch-1 signalling in the
      pathogenesis of psoriasis, Notch-1, DLL-4, Jagged-1, Hrt-1/Hrt-2, A-SAA, Factor
      VIII and vascular endothelial growth factor (VEGF) mRNA and/or protein expression
      in psoriasis skin biopsies, serum and dHMVEC were assessed by immunohistology,
      dual-immunofluorescence, real-time PCR, ELISA and Western blotting. A-SAA-induced
      angiogenesis and invasion in the presence of Notch-1 siRNA was assessed by
      matrigel tube formation assays and Transwell invasion assay. Increased Notch-1,
      its ligand DLL-4 and Hrt-1 expression were demonstrated in lesional skin compared
      with non-lesional skin, with greatest expression observed in the dermal
      vasculature (P < 0.05). Dual-immunofluorescent staining demonstrated co
      localization of Notch-1 to endothelial cell marker Factor VIII. A significant
      increase in A-SAA levels was demonstrated in psoriasis serum compared with
      healthy control serum (P < 0.05), and A-SAA expression was higher in lesional
      skin compared with non-lesional. In dHMVEC, A-SAA significantly induced Jagged-1,
      Hrt-1 and VEGF mRNA expression (P < 0.05) and activated Notch-1 IC indicative of
      transcriptional regulation. In contrast, A-SAA significantly inhibited DLL-4 mRNA
      expression (P < 0.05). Finally A-SAA-induced angiogenesis and invasion were
      inhibited by Notch-1 siRNA (P < 0.05). Notch receptor-ligand interactions mediate
      vascular dysfunction in psoriasis and may represent a potential therapeutic
      target. 

PMID- 24330354
TI  - Differential localization and characterization of functional calcitonin gene
      related peptide receptors in human subcutaneous arteries.
AB  - AIM: Calcitonin gene-related peptide (CGRP) and its receptor are widely
      distributed within the circulation and the mechanism behind its vasodilation not
      only differs from one animal species to another but is also dependent on the type
      and size of vessel. The present study examines the nature of CGRP-induced
      vasodilation, characteristics of the CGRP receptor antagonist telcagepant and
      localization of the key components calcitonin receptor-like receptor (CLR) and
      receptor activity modifying protein 1 (RAMP1) of the CGRP receptor in human
      subcutaneous arteries. METHODS: CGRP-induced vasodilation and receptor
      localization in human subcutaneous arteries were studied by wire myograph in the
      presence and absence of the CGRP receptor antagonist telcagepant and
      immunohistochemistry respectively. RESULTS: At concentrations of 1, 3, 5, 10 and
      30 nm, telcagepant had a competitive antagonist-like behaviour characterized by a
      parallel rightwards shift in the log CGRP concentration-tension/calcium curve
      with no depression of the maximal relaxation. CGRP-induced vasodilation was not
      affected by mechanical removal of the endothelium or addition of L-NG
      nitroarginine methyl ester and indomethacin, antagonists for synthesis of nitric
      oxide and prostaglandins, respectively. CLR and RAMP1 were localized in the
      vascular smooth muscle and endothelial cells. CONCLUSION: The present results
      indicate that CGRP exerts its vasodilatory effect in human subcutaneous arteries
      by binding to its receptors located on the smooth muscle cells and is suggested
      to be endothelium-independent. In conclusion, these results underline the dynamic
      distribution of CGRP receptor components in the human circulation reflecting the
      important role of CGRP in fine tuning of the blood flow in resistance arteries.

PMID- 24330355
TI  - Detection of attractors of large Boolean networks via exhaustive enumeration of
      appropriate subspaces of the state space.
AB  - BACKGROUND: Boolean models are increasingly used to study biological signaling
      networks. In a Boolean network, nodes represent biological entities such as
      genes, proteins or protein complexes, and edges indicate activating or inhibiting
      influences of one node towards another. Depending on the input of activators or
      inhibitors, Boolean networks categorize nodes as either active or inactive. The
      formalism is appealing because for many biological relationships, we lack
      quantitative information about binding constants or kinetic parameters and can
      only rely on a qualitative description of the type "A activates (or inhibits) B".
      A central aim of Boolean network analysis is the determination of attractors
      (steady states and/or cycles). This problem is known to be computationally
      complex, its most important parameter being the number of network nodes. Various
      algorithms tackle it with considerable success. In this paper we present an
      algorithm, which extends the size of analyzable networks thanks to simple and
      intuitive arguments. RESULTS: We present lnet, a software package which, in fully
      asynchronous updating mode and without any network reduction, detects the fixed
      states of Boolean networks with up to 150 nodes and a good part of any present
      cycles for networks with up to half the above number of nodes. The algorithm goes
      through a complete enumeration of the states of appropriately selected subspaces
      of the entire network state space. The size of these relevant subspaces is small
      compared to the full network state space, allowing the analysis of large
      networks. The subspaces scanned for the analyses of cycles are larger, reducing
      the size of accessible networks. Importantly, inherent in cycle detection is a
      classification scheme based on the number of non-frozen nodes of the cycle member
      states, with cycles characterized by fewer non-frozen nodes being easier to
      detect. It is further argued that these detectable cycles are also the
      biologically more important ones. Furthermore, lnet also provides standard
      Boolean analysis features such as node loop detection. CONCLUSIONS: lnet is a
      software package that facilitates the analysis of large Boolean networks. Its
      intuitive approach helps to better understand the network in question.

PMID- 24330356
TI  - Pre-operative cytodiagnosis of follicular thyroid carcinoma with mandibular
      metastasis presenting as gingival swelling.

PMID- 24330357
TI  - In vitro neuroprotective potential of four medicinal plants against rotenone
      induced toxicity in SH-SY5Y neuroblastoma cells.
AB  - BACKGROUND: Lannea schweinfurthii, Zanthoxylum capense, Scadoxus puniceus and
      Crinum bulbispermum are used traditionally to treat neurological disorders. The
      aim of this study was to evaluate the cytoprotective potential of the four
      plants, after induction of toxicity using rotenone, in SH-SY5Y neuroblastoma
      cells. METHODS: Cytotoxicity of the plant extracts and rotenone was assessed
      using the sulforhodamine B (SRB) assay. Fluorometry was used to measure
      intracellular redox state (reactive oxygen species (ROS) and intracellular
      glutathione content), mitochondrial membrane potential (MMP) and caspase-3
      activity, as a marker of apoptotic cell death. RESULTS: Of the tested plants, the
      methanol extract of Z. capense was the least cytotoxic; LC50 121.3 +/- 6.97
      MUg/ml, while S. puniceus methanol extract was the most cytotoxic; LC50 20.75 +/-
      1.47 MUg/ml. Rotenone reduced intracellular ROS levels after 24 h exposure. Pre
      treating cells with S. puniceus and C. bulbispermum extracts reversed the effects
      of rotenone on intracellular ROS levels. Rotenone exposure also decreased
      intracellular glutathione levels, which was counteracted by pre-treatment with
      any one of the extracts. MMP was reduced by rotenone, which was neutralized by
      pre-treatment with C. bulbispermum ethyl acetate extract. All extracts inhibited
      rotenone-induced activation of caspase-3. CONCLUSION: The studied plants
      demonstrated anti-apoptotic activity and restored intracellular glutathione
      content following rotenone treatment, suggesting that they may possess
      neuroprotective properties.

PMID- 24330358
TI  - Delayed sleep phase syndrome in adolescents: prevalence and correlates in a large
      population based study.
AB  - BACKGROUND: The aims of this study were to estimate the prevalence of Delayed
      Sleep Phase Syndrome (DSPS) in adolescence, and to examine the association to
      insomnia and school non-attendance. METHODS: Data stem from a large population
      based study in Hordaland County in Norway conducted in 2012, the ung@hordaland
      study. In all, 10,220 adolescents aged 16-18 years (54% girls) provided self
      reported data on a range of sleep parameters: DSPS was defined according to the
      International Classification of Sleep Disorders, Revised (ICSD-R) criteria, while
      insomnia was defined according to the Quantitative Criteria for Insomnia. Other
      sleep parameters included time in bed, sleep duration, sleep efficiency,
      oversleeping, sleep onset latency, wake after sleep onset, subjective sleep need,
      sleep deficiency, sleepiness and tiredness. Sleep data were calculated separately
      for weekdays and weekends. Data on school non-attendance were provided by
      official registers. RESULTS: The prevalence of DSPS was 3.3%, and significantly
      higher among girls (3.7%) than boys (2.7%). There was a strong overlap between
      DSPS and insomnia, with more than half of the adolescents with DSPS also meeting
      the criteria for insomnia (53.8% for boys and 57.1% for girls). Adolescents with
      DSPS had significantly higher odds ratios (OR) of non-attendance at school. After
      adjusting for sociodeographical factors, insomnia and depression, the adjusted
      ORs for days of non-attendance were OR = 3.22 (95% CI: 1.94-5.34) for boys and OR
      = 1.87 (95% CI: 1.25-2.80) for girls. A similar effect was found for hours of non
      attendance for boys, with an adjusted OR = 3.05 (95% CI: 1.89-4.92). The effect
      for girls was no longer significant after full adjustment (OR =1.48 [95% CI: 0.94
      2.32]). CONCLUSIONS: This is one of the first studies to estimate the prevalence
      of DSPS in adolescents. The high prevalence of DSPS, and overlap with insomnia,
      in combination with the odds of school non-attendance, suggest that a broad and
      thorough clinical approach is warranted when adolescents present with symptoms of
      DSPS.

PMID- 24330359
TI  - Predictive testing: more than just another test.

PMID- 24330360
TI  - Hip fracture in Australia: missed opportunities and a chance to improve care.

PMID- 24330361
TI  - Advances in the management of hepatitis C.
AB  - Significant advances have recently been made in the management of hepatitis C
      virus (HCV) with many of the changes now part of routine clinical practice. These
      include the use of non-invasive methods to assess liver fibrosis, interleukin 28B
      genotype testing to predict interferon responsiveness and the use of new anti
      viral regimens for HCV genotype 1. Two new antiviral agents (boceprevir and
      telaprevir) have recently become available in Australia. These protease
      inhibitors are used in combination with pegylated interferon and ribavirin as
      triple therapy for genotype 1 HCV. This combination increases sustained
      virological response from approximately 45-50% to 66-75% in treatment naive
      patients. However, these new regimens present novel challenges including
      complicated treatment algorithms based on virological response, numerous drug
      interactions and additional side effects especially in patients with advanced
      fibrosis. The protease inhibitors are the first of many antiviral drugs to become
      available to treat HCV, heralding the arrival of new agents that will offer
      greater chances of cure with improved safety and tolerability compared with
      current therapies. 

PMID- 24330362
TI  - Indian-born patients attending a sexual health clinic in Australia have differing
      characteristics to their Australian-born counterparts.
AB  - We report a retrospective cross-sectional study from Western Sydney that assessed
      the sexual health characteristics of Indian-born patients attending sexual health
      services compared with Australian-born controls. The sexual health needs of
      Indian-born patients differed significantly from controls with those born in
      India reporting more sexual dysfunction and controls having more sexually
      transmitted infections (STI). These issues should be considered when delivering
      services to people from culturally and linguistically diverse backgrounds.

PMID- 24330363
TI  - Distal renal tubular acidosis associated with Sjogren syndrome.
AB  - Renal tubular acidosis is a common cause of normal anion gap metabolic acidosis
      but these disorders can be easily missed or misdiagnosed. We highlight the
      approach to assessing renal tubular acidosis by discussing a case study with a
      temporal data set collected over more than 5 weeks. We highlight the principles
      and the necessary information required for a diagnosis of classic distal renal
      tubular acidosis. We also briefly review several aspects of type 1 renal tubular
      acidosis related to autoimmune disease, drugs and thyroid disorders. 

PMID- 24330364
TI  - General health of opioid substitution therapy clients.
AB  - Five common medical conditions among opioid substitution therapy (OST) clients
      were assessed during a health promotion event held at a tertiary hospital-based
      OST clinic in Sydney, Australia. Data were collected anthropometrically (body
      mass index and waist circumference), using spirometry, electrocardiogram, Pap
      test histories, Fibroscan and medical record review. Assessments were undertaken
      by specialised hospital staff. Abnormal results were found for 17% of those who
      underwent an electrocardiogram, 60% were anti-hepatitis C virus positive (40%
      were viraemic), fibrosis was detected in one-third (7% severe fibrosis and 18%
      cirrhosis), chronic obstructive pulmonary disease was detected among 30% of
      participants with 7% at Global Initiative for Chronic Obstructive Lung Disease
      stage II and 2% at stage III. Forty-seven percent of the female respondents
      reported that they had not had a Pap test in the previous 2 years. Findings
      indicate that OST clients suffer several health problems that OST clinics are
      well placed to identify and provide support for referrals.

PMID- 24330365
TI  - Two rare cases of Epstein-Barr virus-associated lymphoproliferative disorders in
      inflammatory bowel disease patients on thiopurines and other immunosuppressive
      medications.
AB  - The setting of chronic immunosuppression in inflammatory bowel disease (IBD) may
      promote the proliferation of Epstein-Barr virus-positive neoplastic clones. We
      report two rare cases of Epstein-Barr virus-associated lymphoproliferative
      disorder in IBD patients: one resembled lymphomatoid granulomatosis, and the
      other was a lymphoma resembling Hodgkin lymphoma. There are currently no
      guidelines for the prevention of lymphoproliferative disorder in IBD patients on
      immunosuppressive therapy. 

PMID- 24330366
TI  - Mycobacterium mimicking metastatic melanoma.
AB  - We present three patients with lung nodules with an antecedent history of primary
      cutaneous melanoma or metastasis of melanoma to extrathoracic lymph nodes. Based
      on radiological findings, it was suspected that these patients had metastatic
      disease. Subsequent investigations confirmed the cause of the nodules was non
      tuberculous mycobacterial infection. We discuss the similarities in symptoms and
      radiological features between atypical mycobacterial infections and metastatic
      disease and why a biopsy is important prior to planning a patient's treatment. 

PMID- 24330367
TI  - Product information for generic drugs: old, unloved and sometimes unsafe.
AB  - Product information is often at odds with current evidence and guidelines and
      inconsistent between products and within classes. There is no single 'owner'
      responsible for up-to-date medicines product information. Outdated product
      information increases the risk of inappropriate prescribing. 

PMID- 24330368
TI  - Drug-induced photo-onycholysis: an often-neglected phenomenon.

PMID- 24330369
TI  - Doctor knowledge and attitudes to donation after cardiac death.

PMID- 24330370
TI  - Author reply: To PMID 23841760.

PMID- 24330371
TI  - Consider ceasing tenofovir in patients with proteinuria prior to nephrology
      review.

PMID- 24330372
TI  - Author reply: To PMID 22931386.

PMID- 24330373
TI  - Private hospitals and physician education.

PMID- 24330374
TI  - Author reply: To PMID 22827884.

PMID- 24330375
TI  - On-road driving assessment in dementia.

PMID- 24330376
TI  - Author reply: To PMID 23745993.

PMID- 24330377
TI  - A significant gap still exists between clinical guidelines and practice for hip
      and knee arthroplasty.

PMID- 24330378
TI  - Chickenpox and stroke in children: case studies and literature review.
AB  - Postvaricella cerebral arteriopathy (PVCA) presents with acute haemiparesis
      and/or haemidistonia, caused by ischaemic lesions of internal capsule and/or
      basal ganglia, related to stenosis of proximal middle and/or anterior cerebral
      arteries. Anti-aggregant drugs are recommended to prevent thrombus expansion and
      recurrent stroke, but neurologic outcome is usually good regardless of the
      therapeutic approach. CONCLUSION: Chickenpox should be considered in differential
      diagnosis of ischaemic stroke in healthy children who fit the clinical and
      radiological typical profile of PVCA.

PMID- 24330379
TI  - Female vulnerability for thyroid function abnormality in bipolar disorder: role
      of lithium treatment.
AB  - BACKGROUND: Previous studies have provided evidence of subtle thyroid hormone
      metabolism abnormalities in patients with mood disorders. Although these studies
      are informative, the precise role of the hypothalamic-pituitary-thyroid axis in
      bipolar disorder, especially in women, remains unclear. We sought to further
      corroborate thyroid function in patients with bipolar disorder in comparison to
      patients with other psychiatric, as well as non-psychiatric, diagnoses. METHODS:
      In this retrospective, cross-sectional, naturalistic study, serum thyroid
      stimulating hormone (TSH) levels in a total sample of 3,204 patients were
      compared. The study sample included patients with bipolar disorder (n = 469),
      unipolar depression (n = 615), and other psychiatric diagnoses (n = 999),
      patients from endocrinology clinics (n = 645), and patients from dermatology
      clinics (n = 476). Analyses were completed using two different normal ranges for
      TDH: a high normal range (0.4-5.0 MUIU/mL) and a low normal range (0.3-3.0
      MUIU/mL). RESULTS: Patients with bipolar disorder showed significantly higher
      serum TSH levels compared to all other groups. In women, the rate of above normal
      range TSH was highest in patients with bipolar disorder for both high (5.0
      MUIU/mL; 12.1%) and low (3.0 MUIU/mL; 30.4%) upper normal limits. In patients
      with bipolar disorder, serum TSH levels did not differ significantly between
      different mood states. In the lithium-treated patients (n = 240), a significantly
      lower percentage of women (55.9%) compared to men (71.2%) fell within the 0.3-3.0
      MUIU/mL normal TSH window (p = 0.016). For the high normal range (0.4-5.0
      MUIU/mL), serum lithium levels above 0.8 mmol/L were associated with a
      significantly lower proportion of female patients (59.2%) falling within the
      normal range than male patients (88.9%). Non-lithium treatment was not associated
      with a gender difference. CONCLUSIONS: Our findings show a higher rate of TSH
      abnormality in patients with bipolar disorder, particularly those taking lithium,
      compared to those with other psychiatric and medical conditions. Lithium
      associated thyroid dysregulation occurs more frequently in female patients. Using
      the low normal range TSH values at follow-up can increase sensitivity in
      recognizing hyperthyroidism in lithium-treated female patients, and help in
      preventing the development of subclinical hypothyroidism and an adverse course of
      illness.

PMID- 24330380
TI  - Effectiveness of different intracanal irrigation techniques in removing
      intracanal paste medicaments.
AB  - This study aimed to compare the effectiveness of different intracanal irrigation
      techniques in removing intracanal medicaments prior to obturation. A total of 168
      single roots were prepared with ProTaper(r) rotary files and medicament pastes
      applied (Ledermix(r), Odontopaste(r), Doxypaste and Pulpdent(r)), left in for 2
      weeks, then removed using filing followed by one of four methods: irrigation with
      an open-ended notched irrigation needle (Appli-Vac) either at the working length
      or 5 mm from the canal orifice, or the Max-I-probe or EndoActivator(r) at the
      working length. Following the removal of medicaments, the roots were split into
      two and the internal surfaces photographed, for digital image analysis of the
      overall percentage of residual medicament. With the exception of canals irrigated
      5 mm apical to the root canal orifice, all four irrigation techniques achieved an
      average of 95% for removal of Ledermix(r), Odontopaste(r) and Doxypaste. Calcium
      hydroxide paste was the most difficult medicament to remove, with no difference
      between irrigation techniques. Up to 27% of the Pulpdent(r) material remained
      after irrigation. No irrigation technique could completely remove all traces of
      medicaments. The position of the irrigational needle and the type of medicament
      used are key factors, which influence the effectiveness of irrigation in removing
      medicaments.

PMID- 24330381
TI  - Ropivacaine 0.1% versus 0.2% for continuous lumbar plexus nerve block infusions
      following total hip arthroplasty: a randomized, double blinded study.
AB  - OBJECTIVE: Continuous lumbar plexus blocks provide excellent analgesia for total
      hip arthroplasty (THA), but their utility has been questioned as they may
      increase motor weakness. The aim of this study was to compare the efficacy of two
      different concentrations of ropivacaine on both postoperative analgesia and motor
      function. METHODS: Thirty patients were examined in this prospective, single
      center, double-blinded, parallel group, comparative, randomized controlled trial
      in patients undergoing primary THA. Lumbar plexus catheters were inserted
      preoperatively. After surgery, patients were randomly assigned to receive an
      infusion of ropivacaine at a concentration of either 0.1% (group 0.1%) or 0.2%
      (group 0.2%) at a standardized volume of 7 mL per hour for 24 hours. Patients
      were also given free access to patient-controlled analgesia hydromorphone for 24
      hours, supplemental intravenous (IV) opiates, and boluses of their assigned local
      anesthetic concentration via the lumbar plexus catheter. The primary endpoint was
      total hydromorphone consumption in 24 hours. Secondary endpoints included pain
      scores, sensory and motor function, and patient satisfaction. RESULTS: There was
      no significant difference in hydromorphone consumption in the first 24 hours
      postoperatively (mean [95% confidence interval]) between group 0.1% (8.02 mg
      [6.02-10.02]) and group 0.2% (8.21 mg [5.75-10.69], P = 0.90). The volume of
      local anesthetic received, pain scores, sensory and motor function, and patient
      satisfaction did not vary between groups. CONCLUSIONS: Following primary THA,
      lumbar plexus perineural infusion of 0.1% ropivacaine provided similar benefits
      for postoperative analgesia and functional recovery as 0.2% ropivacaine.

PMID- 24330382
TI  - Exophiala deep fungal infection complicating dermatitis artefacta of the arms
      responding to itraconazole.

PMID- 24330383
TI  - Massive congenital choledocal cyst.

PMID- 24330384
TI  - Clinical courses and predictors of outcomes in patients with monoarthritis: a
      retrospective study of 171 cases.
AB  - OBJECTIVES: To evaluate the clinical courses and outcomes of patients with
      monoarthritis and to investigate the predictive factors of clinical outcomes.
      METHODS: A retrospective analysis was performed of 171 patients with chronic
      monoarthritis at a single tertiary hospital between January 2001 and January
      2011. Baseline characteristics, radiographic findings and the clinical course
      were reviewed. RESULTS: The most commonly involved joints were the knees (24.0%),
      followed by the wrists (22.8%) and ankles (18.7%). A final diagnosis was
      established in 74 (43.3%) patients. Thirty-one (18.1%) patients were diagnosed
      with rheumatoid arthritis (RA), 23 (13.5%) with peripheral spondyloarthritis
      (SpA), and 19 (11.1%) with Behcet's disease (BD). Among 108 patients who were
      initially undiagnosed, 85 (78.7%) patients remained with undiagnosed
      monoarthritis, with relatively shorter symptom durations and requiring less
      treatment. The initially involved joint was a predictive factor for the final
      diagnosis: the wrist joint for RA (odds ratio [OR] 11.58, P < 0.001), the ankle
      joint for SpA (OR 6.19, P < 0.001), and the knee joint for BD (OR 3.43, P =
      0.014). Bony erosion at baseline was associated with progression to oligo- or
      polyarthritis (OR 2.88, P = 0.030) and with radiographic progression.
      CONCLUSIONS: In patients presenting with monoarthritis, a final diagnosis was
      established in less than half of the patients, and a majority of undiagnosed
      patients showed benign clinical courses. The initially involved joint and the
      presence of erosion at baseline were predictors of the final diagnosis and of
      clinical outcomes.

PMID- 24330385
TI  - Exploring differential item functioning in the SF-36 by demographic, clinical,
      psychological and social factors in an osteoarthritis population.
AB  - BACKGROUND: The SF-36 is a very commonly used generic measure of health outcome
      in osteoarthritis (OA). An important, but frequently overlooked, aspect of
      validating health outcome measures is to establish if items work in the same way
      across subgroup of a population. That is, if respondents have the same 'true'
      level of outcome, does the item give the same score in different subgroups or is
      it biased towards one subgroup or another. Differential item functioning (DIF)
      can identify items that may be biased for one group or another and has been
      applied to measuring patient reported outcomes. Items may show DIF for different
      conditions and between cultures, however the SF-36 has not been specifically
      examined in an osteoarthritis population nor in a UK population. Hence, the aim
      of the study was to apply the DIF method to the SF-36 for a UK OA population.
      METHODS: The sample comprised a community sample of 763 people with OA who
      participated in the Somerset and Avon Survey of Health. The SF-36 was explored
      for DIF with respect to demographic, social, clinical and psychological factors.
      Well developed ordinal regression models were used to identify DIF items.
      RESULTS: DIF items were found by age (6 items), employment status (6 items),
      social class (2 items), mood (2 items), hip v knee (2 items), social deprivation
      (1 item) and body mass index (1 item). Although the impact of the DIF items
      rarely had a significant effect on the conclusions of group comparisons, in most
      cases there was a significant change in effect size. CONCLUSIONS: Overall, the SF
      36 performed well with only a small number of DIF items identified, a reassuring
      finding in view of the frequent use of the SF-36 in OA. Nevertheless, where DIF
      items were identified it would be advisable to analyse data taking account of DIF
      items, especially when age effects are the focus of interest.

PMID- 24330386
TI  - Stroke knowledge among diabetics: a cross-sectional study on the influence of
      age, gender, education, and migration status.
AB  - BACKGROUND: Stroke campaigns are educating about the need to immediately contact
      the emergency medical system if symptoms occur. Despite higher stroke rates among
      patients with diabetics and some migrant populations, there are few data about
      stroke knowledge in these groups. METHODS: We performed a cross-sectional
      questionnaire survey among 250 diabetes patients from Germany and Turkey in a
      primary care and diabetes practice center. The two-page questionnaire asked for
      stroke knowledge and socio-demographic data. Also, medical and communication data
      were obtained. Stroke knowledge was defined as good if a participant knew (1) at
      least two stroke symptoms (good symptom knowledge) and (2) that immediate
      hospital admission or an emergency call is necessary in case of stroke symptoms
      (good action knowledge). RESULTS: A total of 231 of 250 patients took part in the
      survey (participation rate 92.4%) with 134 natives (53.6%), 84 migrants from
      Turkey (33.6%) and 13 migrants (5.2%) from other countries. Comparing natives and
      migrants from Turkey good symptom knowledge was documented in 52.8% of the
      participants, good action knowledge in 67.9%, and good stroke knowledge in nearly
      forty percent (39.4%) of patients (n = 218). A logistic regression analysis
      showed better stroke knowledge if patients were younger than 61 years, had good
      language abilities and were living in an one-generation household (p < 0.05),
      while gender, years since migration and diabetes control did not play a role.
      CONCLUSIONS: We documented stroke knowledge deficits among patients with
      diabetes, both natives and migrants. Additional information strategies for these
      high risk populations are needed.

PMID- 24330387
TI  - Quality of life in patients at first time visit for sleep disorders of breathing
      at a sleep centre.
AB  - INTRODUCTION: Sleep-disordered breathing adversely affects daytime alertness and
      cognition. Obstructive sleep apnea (OSA) patients have several typical symptoms
      including habitual snoring, excessive daytime sleepiness, fatigue, lack of
      concentration, memory impairment, and at times psychological disturbances. We
      evaluated different aspects in the health related quality of life (HRQoL) in
      subjects referred to our sleep laboratory for their first examination for
      suspicion of OSA. METHODS: One hundred ninety-eight consecutive outpatients (152
      M) (mean age 52.7 +/- 12.8 years, range 18-82 years; mean BMI 31.0 +/- 6.5
      kg/m(2), range 17.3-57.8 kg/m(2) were evaluated with two self-reported
      questionnaires for HRQoL assessment: Psychological General Well-Being Index
      (PGWBI), that asses anxiety, depressed mood, positive well-being, self-control,
      general health, vitality, and 12-Item Short-Form Health Survey (SF-12),
      consisting assesses of Physical and Mental Component Summaries (PCS and MCS).
      Epworth Sleepiness Scale (ESS) was used to assess daytime sleepiness before
      nocturnal diagnostic examination. RESULTS: Subjects showed variable HRQoL scores.
      HRQoL was worse in women than men and it decreased with age. No relation was
      found with AHI severity (range 0-129 n/h). BMI and TSat90 (range 0-87.9%)
      affected physical health perception (SF-12 PCS). Furthermore TSat90 influenced
      PGWBI Vitality subscale. Subjects with ESS > 10 showed a worse HRQoL profile (p <
      0.001) in SF-12 and in PGWBI. Multiple regression analysis showed that age, BMI
      and ESS were significant predictors of SF-12 PCS (p < 0.001; r(2) = 0.23).
      CONCLUSIONS: A worse HRQoL perception among subjects referred for OSA suspicion
      was not related to disease severity. BMI and hypoxemia influenced only some HRQoL
      dimensions, while excessive daytime sleepiness worsens all HRQoL components
      considered.

PMID- 24330388
TI  - General practitioners' experiences and perceptions of benzodiazepine prescribing:
      systematic review and meta-synthesis.
AB  - BACKGROUND: Benzodiazepines are often prescribed long-term inappropriately. We
      aimed to systematically review and meta-synthesise qualitative studies exploring
      clinicians' experiences and perceptions of benzodiazepine prescribing to build an
      explanatory model of processes underlying current prescribing practices. METHODS:
      We searched seven electronic databases for qualitative studies in Western primary
      care settings published in a European language between January 1990 and August
      2011 analysing GP or practice nurse experiences of benzodiazepine prescribing. We
      assessed study quality using the Critical Appraisal Skills Programme Checklist.
      We analysed findings using thematic synthesis. RESULTS: We included eight studies
      from seven countries published between 1993 and 2010. Benzodiazepine prescribing
      decisions are complex, uncomfortable, and demanding, taken within the constraints
      of daily general practice. Different GPs varied in the extent to which they were
      willing to prescribe benzodiazepines, and individual GPs' approaches also varied.
      GPs were ambivalent in their attitude towards prescribing benzodiazepines and
      inconsistently applied management strategies for their use. This was due to the
      changing context of prescribing, differing perceptions of the role and
      responsibility of the GP, variation in GPs' attitudes to benzodiazepines,
      perceived lack of alternative treatment options, GPs' perception of patient
      expectations and the doctor-patient relationship. GPs faced different challenges
      in managing initiation, continuation and withdrawal of benzodiazepines.
      CONCLUSION: We have developed a model which could be used to inform future
      interventions to improve adherence to benzodiazepine prescribing guidance and
      improve prescribing through education and training of professionals on
      benzodiazepine use and withdrawal, greater provision of alternatives to drugs,
      reflective practice, and better communication with patients.

PMID- 24330390
TI  - Absence of primary cilia in cell cycle-arrested human breast cancer cells.
AB  - Previous studies using cultured cells showed that primary cilia are present in
      quiescent cells, but are absent in proliferating cells. We studied here the
      relationship between the presence or absence of primary cilia and the cell cycle
      arrest of normal epithelial cells and cancer cells in the human normal breast and
      breast cancer tissues. In normal breast tissues, although most epithelial cells
      were nonproliferating as estimated by the immunofluorescence staining of the
      proliferation marker Ki-67, primary cilia were present only in 20-40% of the
      epithelial cells. In breast cancer tissues, primary cilia were not observed in
      any of the breast cancer cells. Furthermore, primary cilia were hardly observed
      in the nonproliferating cancer cells in the orthotopic and metastatic human
      breast cancer xenograft tumors in mice. These results indicate that the absence
      of primary cilia does not necessarily represent the proliferating phases of
      normal epithelial cells and cancer cells.

PMID- 24330389
TI  - Disruption of GRM1-mediated signalling using riluzole results in DNA damage in
      melanoma cells.
AB  - Gain of function of the neuronal receptor, metabotropic glutamate receptor 1
      (Grm1), was sufficient to induce melanocytic transformation in vitro and
      spontaneous melanoma development in vivo when ectopically expressed in
      melanocytes. The human form of this receptor, GRM1, has been shown to be
      ectopically expressed in a subset of human melanomas but not benign nevi or
      normal melanocytes, suggesting that misregulation of GRM1 is involved in the
      pathogenesis of certain human melanomas. Sustained stimulation of Grm1 by the
      ligand, glutamate, is required for the maintenance of transformed phenotypes in
      vitro and tumorigenicity in vivo. In this study, we investigate the mechanism of
      an inhibitor of glutamate release, riluzole, on human melanoma cells that express
      metabotropic glutamate receptor 1 (GRM1). Various in vitro assays conducted show
      that inhibition of glutamate release in several human melanoma cell lines
      resulted in an increase of oxidative stress and DNA damage response markers. 

PMID- 24330391
TI  - Methylglyoxal resistance in Bacillus subtilis: contributions of bacillithiol
      dependent and independent pathways.
AB  - Methylglyoxal (MG) is a toxic by-product of glycolysis that damages DNA and
      proteins ultimately leading to cell death. Protection from MG is often conferred
      by a glutathione-dependent glyoxalase pathway. However, glutathione is absent
      from the low-GC Gram-positive Firmicutes, such as Bacillus subtilis. The
      identification of bacillithiol (BSH) as the major low-molecular-weight thiol in
      the Firmicutes raises the possibility that BSH is involved in MG detoxification.
      Here, we demonstrate that MG can rapidly and specifically deplete BSH in cells,
      and we identify both BSH-dependent and BSH-independent MG resistance pathways.
      The BSH-dependent pathway utilizes glyoxalase I (GlxA, formerly YwbC) and
      glyoxalase II (GlxB, formerly YurT) to convert MG to d-lactate. The critical step
      in this pathway is the activation of the KhtSTU K(+) efflux pump by the S-lactoyl
      BSH intermediate, which leads to cytoplasmic acidification. We show that
      cytoplasmic acidification is both necessary and sufficient for maximal protection
      from MG. Two additional MG detoxification pathways operate independent of BSH.
      The first involves three enzymes (YdeA, YraA and YfkM) which are predicted to be
      homologues of glyoxalase III that converts MG to d-lactate, and the second
      involves YhdN, previously shown to be a broad specificity aldo-keto reductase
      that converts MG to acetol. 

PMID- 24330392
TI  - Different levels of thyroid hormones between impaired fasting glucose and
      impaired glucose tolerance: free T3 affects the prevalence of impaired fasting
      glucose and impaired glucose tolerance in opposite ways.
AB  - CONTEXT: There is an association between thyroid disorders and diabetes mellitus.
      OBJECTIVE: To investigate thyroid hormone levels in different glucose metabolic
      statuses, analyse relationships between thyroid hormone levels and different
      categories of prediabetes and metabolic parameters within a large euthyroid
      nondiabetic population. METHODS: A total of 3328 subjects without diabetes or
      thyroid dysfunction were included in this cross-sectional study. Subjects were
      divided in to four groups [normal glucose tolerance (NGR), impaired fasting
      glucose (IFG), impaired glucose tolerance (IGT) and combined glucose intolerance
      (CGI)] according to the results of oral glucose tolerance test. Participants were
      then divided into four groups according to the quartile of free T3 (FT3) in their
      blood. RESULTS: Subjects with IFG had higher levels of FT3 and ratio of FT3 to
      FT4 (FT3/FT4), but lower level of free T4 (FT4) than subjects with IGT. FT3/FT4
      was negatively associated with postprandial plasma glucose (PPG) [standardized
      beta (beta) = -0.087; P < 0.001]. The prevalence of IFG and CGI was increased
      with the level of FT3, while the prevalence of IGT was decreased with the level
      of FT3 (P for trend: <0.001, 0.003 and <0.001, respectively). FT3 was negatively
      associated with the risk of IGT (OR = 0.409, 95% CI 0.179-0.935), whereas FT4 was
      positively associated with the risk of IGT (OR = 1.296, 95% CI 1.004-1.673).
      CONCLUSIONS: Free thyroid hormone levels were different between subjects with IFG
      and IGT. FT3 affects the prevalence of IFG and IGT in opposite ways. The
      difference in thyroid hormone levels may play an important role in the different
      pathological mechanisms of IFG and IGT.

PMID- 24330393
TI  - PhaP phasins play a principal role in poly-beta-hydroxybutyrate accumulation in
      free-living Bradyrhizobium japonicum.
AB  - BACKGROUND: Bradyrhizobium japonicum USDA110, a soybean symbiont, is capable of
      accumulating a large amount of poly-beta-hydroxybutyrate (PHB) as an
      intracellular carbon storage polymer during free-living growth. Within the genome
      of USDA110, there are a number of genes annotated as paralogs of proteins
      involved in PHB metabolism, including its biosynthesis, degradation, and
      stabilization of its granules. They include two phbA paralogs encoding 3-ketoacyl
      CoA thiolase, two phbB paralogs encoding acetoacetylCoA reductase, five phbC
      paralogs encoding PHB synthase, two phaZ paralogs encoding PHB depolymerase, at
      least four phaP phasin paralogs for stabilization of PHB granules, and one phaR
      encoding a putative transcriptional repressor to control phaP expression.
      RESULTS: Quantitative reverse-transcriptase PCR analyses of RNA samples prepared
      from cells grown using three different media revealed that PHB accumulation was
      related neither to redundancy nor expression levels of the phbA, phbB, phbC, and
      phaZ paralogs for PHB-synthesis and degradation. On the other hand, at least
      three of the phaP paralogs, involved in the growth and stabilization of PHB
      granules, were induced under PHB accumulating conditions. Moreover, the most
      prominently induced phasin exhibited the highest affinity to PHB in vitro; it was
      able to displace PhaR previously bound to PHB. CONCLUSIONS: These results suggest
      that PHB accumulation in free-living B. japonicum USDA110 may not be achieved by
      controlling production and degradation of PHB. In contrast, it is achieved by
      stabilizing granules autonomously produced in an environment of excess carbon
      sources together with restricted nitrogen sources.

PMID- 24330394
TI  - Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates
      infection of CD4pos T cells and macrophages.
AB  - BACKGROUND: Sialic acid-binding Ig-like lectin-7 (Siglec-7) expression is
      strongly reduced on natural killer (NK) cells from HIV-1 infected viremic
      patients. To investigate the mechanism(s) underlying this phenomenon, we
      hypothesized that Siglec-7 could contribute to the infection of CD4pos target
      cells following its interaction with HIV-1 envelope (Env) glycoprotein 120
      (gp120). RESULTS: The ability of Siglec-7 to bind gp120 Env in a sialic acid
      dependent manner facilitates the infection of both T cells and monocyte-derived
      macrophages (MDMs). Indeed, pre-incubation of HIV-1 with soluble Siglec-7
      (sSiglec-7) increases the infection rate of CD4pos T cells, which do not
      constitutively express Siglec-7. Conversely, selective blockade of Siglec-7
      markedly reduces the degree of HIV-1 infection in Siglec-7pos MDMs. Finally, the
      sSiglec-7 amount is increased in the serum of AIDS patients with high levels of
      HIV-1 viremia and inversely correlates with CD4pos T cell counts. CONCLUSIONS:
      Our results show that Siglec-7 binds HIV-1 and contributes to enhance the
      susceptibility to infection of CD4pos T cells and MDMs. This phenomenon plays a
      role in HIV-1 pathogenesis and in disease progression, as suggested by the
      inverse correlation between high serum level of sSiglec-7 and the low CD4pos T
      cell count observed in AIDS patients in the presence of chronic viral
      replication.

PMID- 24330396
TI  - Exercise engagement in people with prediabetes--a qualitative study.
AB  - AIMS AND OBJECTIVES: To explore the experiences of people with prediabetes who
      engage in exercise, from the initiation of exercise to the discontinuation or
      continuation of exercise. BACKGROUND: People with prediabetes are the high-risk
      group for developing type 2 diabetes. Engaging in exercise is an important health
      behaviour to prevent or delay this. However, many people with prediabetes fail to
      develop and maintain a regular exercise regime. DESIGN: A grounded theory study.
      METHODS: Data were collected from August 2011-November 2012. Twenty participants
      with impaired fasting glucose from a medical centre in Taiwan were enrolled in
      this study for in-depth interview. The data were entered into NVivo 8.0
      qualitative data management software after transcription and were analysed by
      constant comparative method. RESULTS: A theory of the process by which people
      with prediabetes approach the development of exercise behaviour was developed,
      comprising four stages: developing awareness, creating the health blueprint,
      action cycle of internal struggle and developing spontaneous regular exercise.
      Developing awareness was the starting point for the process of implementing
      exercise. The core category was action cycle of struggle that all participants
      experienced this stage, and the spontaneous regular exercise was the highest
      level of exercise process. CONCLUSION: It is not easy for people with prediabetes
      to develop a regular exercise regime. Exercise behaviour will be either continued
      or discontinued secondary to driving and resistive forces. RELEVANCE TO CLINICAL
      PRACTICE: This study provides useful information to help practitioners design
      exercise intervention strategies and provide psychological support to people with
      prediabetes.

PMID- 24330395
TI  - The potential of anti-malarial compounds derived from African medicinal plants,
      part I: a pharmacological evaluation of alkaloids and terpenoids.
AB  - Traditional medicine caters for about 80% of the health care needs of many rural
      populations around the world, especially in developing countries. In addition,
      plant-derived compounds have played key roles in drug discovery. Malaria is
      currently a public health concern in many countries in the world due to factors
      such as chemotherapy faced by resistance, poor hygienic conditions, poorly
      managed vector control programmes and no approved vaccines. In this review, an
      attempt has been made to assess the value of African medicinal plants for drug
      discovery by discussing the anti-malarial virtue of the derived phytochemicals
      that have been tested by in vitro and in vivo assays. This survey was focused on
      pure compounds derived from African flora which have exhibited anti-malarial
      properties with activities ranging from "very active" to "weakly active".
      However, only the compounds which showed anti-malarial activities from "very
      active" to "moderately active" are discussed in this review. The activity of 278
      compounds, mainly alkaloids, terpenoids, flavonoids, coumarines, phenolics,
      polyacetylenes, xanthones, quinones, steroids, and lignans have been discussed.
      The first part of this review series covers the activity of 171 compounds
      belonging to the alkaloid and terpenoid classes. Data available in the literature
      indicated that African flora hold an enormous potential for the development of
      phytomedicines for malaria. 

PMID- 24330397
TI  - Cytotoxicity, mode of action and antibacterial activities of selected Saudi
      Arabian medicinal plants.
AB  - BACKGROUND: The flora of Saudi Arabia is one of the richest biodiversity areas in
      the Arabian Peninsula and comprises very important genetic resources of crop and
      medicinal plants. The present study was designed to investigate the cytotoxicity
      and the antibacterial activities of the organic extracts from twenty six Saudi
      Arabian medicinal plants. The study was also extended to the investigation of the
      effects of the extracts from the four best plants, Ononis serrata (SY160),
      Haplophyllum tuberculatum (SY177), Pulicaria crispa (SY179), and Achillea
      beiberstenii (SY-200) on cell cycle distribution, apoptosis, caspases activities
      and mitochondrial function in leukemia CCRF-CEM cell line. METHODS: A resazurin
      assay was used to assess the cytotoxicity of the extracts on a panel of human
      cancer cell lines whilst the microbroth dilution was used to determine the
      minimal inhibitory concentration (MIC) of the samples against twelve bacterial
      strains belonging to four species, Escherichia coli, Enterobacter aerogenes,
      Klebsiella pneumoniae and Pseudomonas aeruginosa. RESULTS: The best activity on
      leukemia cell lines were recorded with SY177 (IC50 of 9.94 MUg/mL) and SY179
      (IC50 of 1.81 MUg/mL) against CCRF-CEM as well as Ach-b (IC50 of 9.30 MUg/mL) and
      SY160 (IC50 of 5.06 MUg/mL) against HL60 cells. The extracts from SY177 and SY179
      were also toxic against the seven solid cancer cell lines studied with the
      highest IC50 values of 31.64 MUg/mL (SY177 against Hep-G2 cells). SY177 and Ach-b
      induced cell cycle arrest in G0/G1 and S phases whilst SY160 and SY179 induced
      arrest in G0/G1 phase. All the four plant extracts induced apoptosis in CCRF-CEM
      cells with the alteration of the mitochondrial membrane potential. In the
      antibacterial assays, only Ach-b displayed moderate antibacterial activities
      against E. coli and E. aerogenes ATCC strains (MIC of 256 MUg/mL), AG100A(TeT)
      and K. pneumoniae ATCC strains (MIC of 128 MUg/mL). CONCLUSIONS: Finally, the
      results of the present investigation provided supportive data for the possible
      use of some Saudi Arabian plants investigated herein, and mostly Haplophyllum
      tuberculatum, Pulicaria crispa, Ononis serrata and Achillea beiberstenii in the
      control of cancer diseases.

PMID- 24330398
TI  - Resveratrol promotes myogenesis and hypertrophy in murine myoblasts.
AB  - BACKGROUND: Nutrigenomics elucidate the ability of bioactive food components to
      influence gene expression, protein synthesis, degradation and post-translational
      modifications.Resveratrol (RSV), natural polyphenol found in grapes and in other
      fruits, has a plethora of health benefits in a variety of human diseases: cardio-
      and neuroprotection, immune regulation, cancer chemoprevention, DNA repair,
      prevention of mitochondrial disorder, avoidance of obesity-related diseases. In
      skeletal muscle, RSV acts on protein catabolism and muscle function, conferring
      resistance against oxidative stress, injury and cell death, but its action
      mechanisms and protein targets in myogenesis process are not completely known.
      Myogenesis is a dynamic multistep process regulated by Myogenic Regulator Factors
      (MRFs), responsible of the commitment of myogenic cell into skeletal muscle:
      mononucleated undifferentiated myoblasts break free from cell cycle, elongate and
      fuse to form multinucleated myotubes. Skeletal muscle hypertrophy can be defined
      as a result of an increase in the size of pre-existing skeletal muscle fibers
      accompanied by increased protein synthesis, mainly regulated by Insulin Like
      Growth Factor 1 (IGF-1), PI3-K/AKT signaling pathways.Aim of this work was the
      study of RSV effects on proliferation, differentiation process and hypertrophy in
      C2C12 murine cells. METHODS: To study proliferative phase, cells were incubated
      in growth medium with/without RSV (0.1 or 25 MUM) until reaching sub confluence
      condition (24, 48, 72 h). To examine differentiation, at 70% confluence, cells
      were transferred in differentiation medium both with/without RSV (0.1 or 25 MUM)
      for 24, 48, 72, 96 hours. After 72 hours of differentiation, the genesis of
      hypertrophy in neo-formed myotubes was analyzed. RESULTS: Data showed that RSV
      regulates cell cycle exit and induces C2C12 muscle differentiation. Furthermore,
      RSV might control MRFs and muscle-specific proteins synthesis. In late
      differentiation, RSV has positive effects on hypertrophy: RSV stimulates IGF-1
      signaling pathway, in particular AKT and ERK 1/2 protein activation, AMPK protein
      level and induces hypertrophic morphological changes in neo-formed myotubes
      modulating cytoskeletal proteins expression. CONCLUSIONS: RSV might control cell
      cycle promoting myogenesis and hypertrophy in vitro, opening a novel field of
      application of RSV in clinical conditions characterized by chronic functional and
      morphological muscle impairment.

PMID- 24330399
TI  - Design of a quasi-experiment on the effectiveness and cost-effectiveness of using
      the child-interview intervention during the investigation following a report of
      child abuse and/or neglect.
AB  - BACKGROUND: In the Netherlands, suspected cases of child maltreatment can be
      reported to an advice and reporting center on child abuse and neglect (Advies- en
      Meldpunt Kindermishandeling or AMK). AMKs investigate these reports, screen for
      problems in the family and its surroundings and refer to child welfare. Over the
      last decades the focus of AMK investigations has changed from an adult-only
      approach to a more child-oriented approach using a Child-Interview intervention.
      The effects and cost-effectiveness of AMK involvement in the Netherlands have
      never been studied. The primary aim of this study is therefore to examine the
      effect of the participation of maltreated children aged 6-18 years in the Child
      Interview intervention on their mental health and quality of life. As a second
      aim, this study will examine the balance between additional costs and effects of
      the Child-Interview intervention in comparison with AMK investigation without the
      Child-Interview intervention (adult-only intervention). DESIGN/METHODS: A quasi
      experiment will be performed consisting of two post-intervention measurements of
      two nonequivalent groups: an intervention group, in which the Child-Interview
      intervention has been used during the AMK investigation, and a control group, in
      which the intervention has not been used (adult-only intervention). Participants
      from an ongoing prospective study on the mental health and quality of life of
      maltreated children after a report to an AMK, will be contacted to complete a
      questionnaire twice. Multivariate regression analyses will be used to determine
      effectiveness of the Child-Interview intervention. The economic evaluation will
      involve a cost-effectiveness analysis and a cost-utility analysis.
      RESULTS/DISCUSSION: This will be the first study to examine the effect of AMK
      involvement in the Netherlands. Using the Child-Interview intervention during AMK
      investigation may prevent or reduce negative outcomes of child maltreatment,
      which may result in a lower consumption of healthcare and other services. In
      addition, the importance of economic evaluations is increasingly recognized, and
      economic evaluations about child maltreatment are scarce. Limitations include the
      risk of potential recall bias and selection bias. TRIAL REGISTRATION: NTR3728,
      funded by ZonMw, project 15700.2012.

PMID- 24330400
TI  - Whole-body fluid distribution in humans during dehydration and recovery, before
      and after humid-heat acclimation induced using controlled hyperthermia.
AB  - AIM: This experiment was designed to test the hypothesis that the plasma volume
      is not selectively defended during exercise- and heat-induced dehydration
      following humid-heat acclimation. METHODS: Eight physically active males were
      heat acclimated (39.8  degrees C, relative humidity 59.2%) using 17 days of
      controlled hyperthermia (core temperature: 38.5  degrees C). Inter-compartmental
      fluid losses and movements were tracked (radioisotopes and Evans blue dye) during
      progressive dehydration (cycling) in these same conditions and also during a
      resting recovery without fluid replacement (28  degrees C), before (day 1),
      during (day 8) and after heat acclimation (day 22). RESULTS: On days 8 and 22,
      there were significant increases in total body water, interstitial fluid and
      plasma volume (P < 0.05), but the intracellular compartments did not change (P >
      0.05). The baseline plasma volume remained expanded throughout: 43.4 [+/-2.6 (day
      1)], 49.1 [+/-2.4 (day 8); P < 0.05] and 48.9 mL kg(-1) [+/-3.0 (day 22); P <
      0.05]. During progressive dehydration, plasma reductions of 9.0% (+/-0.9: day 1),
      12.4% (+/-1.6: day 8) and 13.6% (+/-1.2: day 22) were observed, with day 8 and 22
      losses significantly exceeding day 1 (P < 0.05). During recovery, plasma volume
      restoration commenced, with the intracellular fluid contribution becoming more
      pronounced as acclimation progressed. CONCLUSION: It is concluded that the plasma
      volume was not defended more vigorously following humid-heat acclimation. Indeed,
      a greater fluid loss may well underlie the mechanisms for enhancing plasma volume
      recovery when heat acclimation is induced using the controlled-hyperthermia
      technique.

PMID- 24330402
TI  - Patient-provider communication about gestational weight gain among nulliparous
      women: a qualitative study of the views of obstetricians and first-time pregnant
      women.
AB  - BACKGROUND: In 2009 the Institute of Medicine updated its guidelines for weight
      gain during pregnancy, in part because women of childbearing age now weigh more
      pre-pregnancy and tend to gain more weight during pregnancy than women did when
      the previous set of guidelines were released in 1990. Women who begin pregnancy
      overweight or obese and women who gain weight outside IOM recommendations are at
      risk for poor maternal and fetal health outcomes. With these concerns in mind, we
      examined what obstetricians communicate about gestational weight gain to their
      pregnant patients and how nulliparous patients perceive weight-related counseling
      from their obstetricians. METHODS: We conducted one-on-one, semi-structured
      interviews with 19 nulliparous women and 7 obstetricians recruited from a single
      clinic at a large academic medical center in the United States. Interviews were
      transcribed verbatim and analyzed inductively using thematic analysis. RESULTS:
      We identified 4 major themes: 1) Discussions about the amount and pace of
      gestational weight gain: obstetricians reported variation in the frequency and
      timing of weight-related discussions with patients while most patients said that
      weight was not emphasized by their obstetricians; 2) The content of communication
      about nutrition and physical activity: obstetricians said they discuss nutrition
      and activity with all patients while most patients reported that their
      obstetrician either discussed these topics in general terms or not at all; 3)
      Communication about postpartum weight loss: obstetricians said that they do not
      typically address postpartum weight loss with patients during prenatal visits
      while patients had concerns about postpartum weight; and 4) Patient feelings
      about obstetrician advice: most patients said that their obstetrician does not
      tend to offer "unsolicited advice", instead offering information in response to
      patient questions or concerns. Women were divided about whether they desired more
      advice from their obstetrician on weight gain, nutrition, and activity.
      CONCLUSIONS: Our analysis revealed discrepancies between obstetricians' and
      patients' perceptions of their weight-related clinical interactions. Our findings
      suggest that there is a missed opportunity to use prenatal visits as
      opportunities to discuss healthy eating and exercise during pregnancy, the
      postpartum period, and beyond. Additional research on the design, implementation,
      and testing of interventions to address prenatal nutrition and physical activity
      is warranted.

PMID- 24330401
TI  - iMir: an integrated pipeline for high-throughput analysis of small non-coding RNA
      data obtained by smallRNA-Seq.
AB  - BACKGROUND: Qualitative and quantitative analysis of small non-coding RNAs by
      next generation sequencing (smallRNA-Seq) represents a novel technology
      increasingly used to investigate with high sensitivity and specificity RNA
      population comprising microRNAs and other regulatory small transcripts. Analysis
      of smallRNA-Seq data to gather biologically relevant information, i.e. detection
      and differential expression analysis of known and novel non-coding RNAs, target
      prediction, etc., requires implementation of multiple statistical and
      bioinformatics tools from different sources, each focusing on a specific step of
      the analysis pipeline. As a consequence, the analytical workflow is slowed down
      by the need for continuous interventions by the operator, a critical factor when
      large numbers of datasets need to be analyzed at once. RESULTS: We designed a
      novel modular pipeline (iMir) for comprehensive analysis of smallRNA-Seq data,
      comprising specific tools for adapter trimming, quality filtering, differential
      expression analysis, biological target prediction and other useful options by
      integrating multiple open source modules and resources in an automated workflow.
      As statistics is crucial in deep-sequencing data analysis, we devised and
      integrated in iMir tools based on different statistical approaches to allow the
      operator to analyze data rigorously. The pipeline created here proved to be
      efficient and time-saving than currently available methods and, in addition,
      flexible enough to allow the user to select the preferred combination of
      analytical steps. We present here the results obtained by applying this pipeline
      to analyze simultaneously 6 smallRNA-Seq datasets from either exponentially
      growing or growth-arrested human breast cancer MCF-7 cells, that led to the rapid
      and accurate identification, quantitation and differential expression analysis of
      ~450 miRNAs, including several novel miRNAs and isomiRs, as well as
      identification of the putative mRNA targets of differentially expressed miRNAs.
      In addition, iMir allowed also the identification of ~70 piRNAs (piwi-interacting
      RNAs), some of which differentially expressed in proliferating vs growth arrested
      cells. CONCLUSION: The integrated data analysis pipeline described here is based
      on a reliable, flexible and fully automated workflow, useful to rapidly and
      efficiently analyze high-throughput smallRNA-Seq data, such as those produced by
      the most recent high-performance next generation sequencers. iMir is available at
      http://www.labmedmolge.unisa.it/inglese/research/imir.

PMID- 24330403
TI  - Adverse circulatory effects of passive smoking during infancy: surprisingly
      strong, manifest early, easily avoided.
AB  - AIM: To compare blood pressure reactions (BPR) of infants to mild stress for
      evidence of adverse cardiovascular effects of passive exposure to tobacco smoke
      during pregnancy and early infancy. METHODS: An observational field study
      conducted in Crete. We compared 4- to 6-month olds of lifelong nonsmokers
      minimally (controls, n = 9) or frequently exposed to tobacco smoke (passive
      smokers; n = 10) with those born to habitual smokers (n = 6). Smoke exposure was
      verified biochemically (urine cotinine each trimester and at study). We recorded
      beat-to-beat blood pressure (BP) during brief repositioning manoeuvres performed
      during a daytime nap and analysed BPR (% change in BP during head-up tilt) for
      associations with maternal and infant cotinine. RESULTS: We observed a 20-fold
      difference between BPR of infants of controls versus passive smokers -
      exceptional given number of infants (alpha error/confidence level <10% i.e. power
      >90%). The BPR declined linearly as the infant's (but not mother's) cotinine
      level rose (p = 0.04), indicating abnormal BPR was caused mainly by postnatal
      smoke exposure. Infants of active smokers differed from those of passive smokers.
      CONCLUSION: Cardiovascular effects of passive smoking by a newborn infant
      manifest early on and are exceptionally strong. They can be largely avoided by
      keeping the home smoke rigorously free.

PMID- 24330404
TI  - The effect of population bottlenecks on mutation rate evolution in asexual
      populations.
AB  - In the absence of recombination, a mutator allele can spread through a population
      by hitchhiking with beneficial mutations that appear in its genetic background.
      Theoretical studies over the past decade have shown that the survival and
      fixation probability of beneficial mutations can be severely reduced by
      population size bottlenecks. Here, we use computational modelling and evolution
      experiments with the yeast S. cerevisiae to examine whether population
      bottlenecks can affect mutator dynamics in adapting asexual populations. In
      simulation, we show that population bottlenecks can inhibit mutator hitchhiking
      with beneficial mutations and are most effective at lower beneficial mutation
      supply rates. We then subjected experimental populations of yeast propagated at
      the same effective population size to three different bottleneck regimes and
      observed that the speed of mutator hitchhiking was significantly slower at
      smaller bottlenecks, consistent with our theoretical expectations. Our results,
      thus, suggest that bottlenecks can be an important factor in mutation rate
      evolution and can in certain circumstances act to stabilize or, at least, delay
      the progressive elevation of mutation rates in asexual populations. Additionally,
      our findings provide the first experimental support for the theoretically
      postulated effect of population bottlenecks on beneficial mutations and
      demonstrate the usefulness of studying mutator frequency dynamics for
      understanding the underlying dynamics of fitness-affecting mutations. 

PMID- 24330406
TI  - Prediction of pregabalin-mediated pain response by severity of sleep disturbance
      in patients with painful diabetic neuropathy and post-herpetic neuralgia.
AB  - OBJECTIVE: To evaluate the predictive value of disturbed sleep on the ability of
      pregabalin to reduce pain associated with diabetic peripheral neuropathy (DPN)
      and post-herpetic neuralgia (PHN). DESIGN: A post-hoc analysis of data pooled
      from 16 placebo-controlled trials of pregabalin in patients with DPN or PHN.
      METHODS: Pain relief at endpoint was compared in patients with mild, moderate, or
      severe levels of baseline sleep disturbance. Sleep disturbance was based on a
      scale from 0-10 and scores <4, 4 to 7, and >=7 were classified as mild, moderate,
      and severe, respectively. RESULTS: Pregabalin significantly reduced mean pain
      scores in the DPN (N = 3,056) and PHN (N = 1,471) cohorts (mean placebo-adjusted
      reductions were -0.73 and -1.08 for patients with DPN/PHN, respectively; both P <
      0.05). The greatest extent of pain relief occurred in patients with severe sleep
      interference scores at baseline. Data analyses using the pooled DPN/PHN
      population identified a subset of patients (N = 707) exhibiting marked levels of
      pain relief at endpoint (mean placebo-adjusted reduction of -2.88), all of whom
      had severe sleep interference scores at baseline. Baseline sleep interference
      scores were a moderately good predictor of global patient improvement in response
      to pregabalin treatment in both patient cohorts. Finally, path analysis showed a
      high degree of association between improvements in sleep and pain relief in
      patients with DPN/PHN. CONCLUSION: Overall, these data suggest that the presence
      of comorbid sleep disturbance in patients with DPN/PHN might, in part, predict
      substantial pain relief in response to pregabalin treatment.

PMID- 24330407
TI  - Lingual myoclonus and neuropsychiatric lupus: a new association?

PMID- 24330405
TI  - Inhibition of carnitine palymitoyltransferase1b induces cardiac hypertrophy and
      mortality in mice.
AB  - Recent reports suggest that short-term pharmacological carnitine
      palmitoyltransferase 1 (Cpt1) inhibition improves skeletal muscle glucose
      tolerance and insulin sensitivity. Although this appears promising for the
      treatment of diabetes, these Cpt1 inhibitors are not specific to skeletal muscle
      and target multiple Cpt1 isoforms. To assess the effects of inhibiting the Cpt1b
      isoform we generated mice with a heart- and skeletal muscle-specific deletion of
      the Cpt1b, Cpt1b(HM-/-). These mice seem to develop normally with similar
      bodyweights as control mice. However, premature mortality was observed by 15
      weeks of age in the Cpt1b(HM-/-) mice. The hearts of Cpt1b(HM-/-) mice were four
      times the size of controls. Cpt1b(HM-/-) mice were also subject to stress-induced
      seizures that accompanied an increased risk for premature mortality. Our data
      suggests that prolonged Cpt1b inhibition poses severe cardiac risk and emphasizes
      that attempts to improve insulin sensitivity by targeting Cpt1 with current
      inhibitors is not viable.

PMID- 24330408
TI  - Tryptophan breakdown is increased in euthymic overweight individuals with bipolar
      disorder: a preliminary report.
AB  - OBJECTIVES: Individuals with bipolar disorder (BD) are disproportionately
      affected by symptoms of being overweight and metabolic syndrome when compared to
      the general population. The pertinence of this observation is underscored by
      observations that excess weight is associated with a more complex illness
      presentation, course, and outcome in BD. We present the first preliminary report
      of our BIPFAT study, which explored shared hypothesized pathophysiological
      pathways between being overweight and having BD. METHODS: We investigated the
      tryptophan-kynurenine metabolism pathway as a proxy of dysregulated inflammatory
      homeostasis in euthymic, overweight individuals with BD (n = 78) compared to
      healthy controls (n = 156). RESULTS: Both blood kynurenine concentrations and the
      kynurenine to tryptophan ratio [(Kyn:Trp); an estimate of tryptophan breakdown]
      were significantly higher in the total sample of euthymic patients with BD, with
      greater increases noted in both parameters in the subsample of overweight
      patients with BD. When compared to controls, peripheral neopterin concentrations
      were significantly lower. Within the BD group, there were also significant
      between-group differences in neopterin concentrations, with higher levels in
      those who were overweight and in subjects with BD in the later stages of illness
      compared to earlier stages. CONCLUSIONS: Increased tryptophan breakdown, as well
      as neopterin levels in BD, may be an indirect mediator of immune-mediated
      inflammation. In BD, this may account for the high prevalence of medical
      comorbidities and increased mortality. The observation of increased kynurenine
      levels and Kyn:Trp, and altered circulating neopterin levels provides indirect
      evidence of increased activity of tryptophan-degrading indoleamine 2,3
      dioxygenase in euthymic individuals with BD, underscoring the role of
      inflammatory mediators as a causative and/or consequent factor. More robust
      abnormalities in the overweight subsample underscore the additional inflammatory
      burden of medical comorbidity and suggest a shared pathophysiology as well as a
      mechanism mediating BD and cardiovascular disease.

PMID- 24330410
TI  - Effects of astaxanthin-enriched yeast on mucosal IgA induction in the jejunum and
      ileum of weanling mice.
AB  - The present study was conducted to clarify the effects of astaxanthin-enriched
      yeast on the concentration of immunoglobulin A (IgA), the numbers of IgA antibody
      secreting cells (ASC) and the messenger RNA (mRNA) expression of IgA C-region in
      the jejunum and ileum of weanling mice. Weanling mice were fed rodent feed or
      astaxanthin-enriched yeast-supplemented rodent feed for 7, 14 or 21 days.
      Supplemental astaxanthin-enriched yeast increased the numbers of IgA ASC in the
      jejunum and ileum after 7, 14 and 21 days of treatment. Supplemental astaxanthin
      enriched yeast increased IgA concentrations in the jejunum after 21 days of
      treatment, but IgA concentrations in the ileum were not affected by the
      treatment. The mRNA expressions of IgA C-region in the jejunum after 14 and 21
      days of treatment and the ileum after 14 days of treatment were enhanced by
      supplementation of astaxanthin-enriched yeast. These results indicate that
      supplementation of astaxanthin-enriched yeast is effective to enhance the numbers
      of IgA ASC in the jejunum and ileum and IgA concentrations in the ileum of
      weanling mice. 

PMID- 24330409
TI  - Risk factors for incident hyperuricemia during mid-adulthood in African American
      and white men and women enrolled in the ARIC cohort study.
AB  - BACKGROUND: Increased serum urate levels are associated with poor outcomes
      including but not limited to gout. It is unclear whether serum urate levels are
      the sole predictor of incident hyperuricemia or whether demographic and clinical
      risk factors also predict the development of hyperuricemia. The goal of this
      study was to identify risk factors for incident hyperuricemia over 9 years in a
      population-based study, ARIC. METHODS: ARIC recruited individuals from 4 US
      communities; 8,342 participants who had urate levels <7.0 mg/dL were included in
      this analysis. Risk factors (including baseline, 3-year, and change in urate
      level over 3 years) for 9-year incident hyperuricemia (urate level of >7.0 g/dL)
      were identified using an AIC-based selection approach in a modified Poisson
      regression model. RESULTS: The 9-year cumulative incidence of hyperuricemia was
      4%; men = 5%; women = 3%; African Americans = 6% and whites = 3%. The adjusted
      model included 9 predictors for incident hyperuricemia over 9 years: male sex (RR
      = 1.73 95% CI: 1.36-2.21), African-American race (RR = 1.79 95% CI: 1.37-2.33),
      smoking (RR = 1.27, 95% CI: 0.97-1.67), <HS education (RR = 1.27, 95% CI: 0.99
      1.63), hypertension (RR = 1.65, 95% CI: 1.30-2.09), CHD (RR = 1.57, 95% CI: 0.99
      2.50), obesity (class I RR = 2.37, 95% CI: 1.65-3.41 and >= class II RR = 3.47,
      95% CI: 2.33-5.18), eGFR < 60 (RR = 2.85, 95% CI: 1.62-5.01) and triglycerides
      (Quartile 4 vs. Quartile 1: RR = 2.00, 95% CI: 1.38-2.89). In separate models,
      urate levels at baseline (RR 1 mg/dL increase = 2.33, 95% CI: 1.94-2.80) and 3
      years after baseline (RR for a 1 mg/dL increase = 1.92, 95% CI: 1.78-2.07) were
      associated with incident hyperuricemia after accounting for demographic and
      clinical risk factors. CONCLUSION: Demographic and clinical risk factors that are
      routinely collected as part of regular medical care are jointly associated with
      the development of hyperuricemia.

PMID- 24330411
TI  - How many hypertensive patients can be controlled in "real life": an improvement
      strategy in primary care.
AB  - BACKGROUND: It is well known that hypertension control is non-satisfactory, but
      it is not clear how many hypertensive patients can be controlled in real life. We
      addressed this question implementing a simple, multifaceted improvement strategy
      in family practice. METHODS: Eighteen General Practitioner (GPs) agreed upon a
      simple improvement strategy including: 1) the use of occasional direct/indirect
      contacts (prescription refilling) to decrease missing blood pressure (BP)
      recording, and to increase therapeutic adherence, 2) the use of home BP
      measurements in non-controlled patients, 3) the addition of a new drug in non
      controlled, but adequately adherent patients. Results were assessed after one
      year by automatic data extraction from the clinical records of all hypertensive
      subjects. RESULTS: The patients with a diagnosis of hypertension increased from
      6.309 (age 58.5 +/- 12.4; M 45.5%) to 6.717 (age 58.6 +/- 12.9; M 45.7%):
      prevalence 25.3% to 27.0%. The BP recording increased: 4,305 patients (68.2%) vs
      4,948 patients (78.4%) (+ 10.2%, ci 9.4%-10.9%; p < 0.001), as well as the BP
      control: 3,203 (50.8% of all the diagnosed hypertensive patients and 74.4% of the
      subjects with recorded BP value) vs 4,043 (64.1% of all the diagnosed
      hypertensive patients and 81.7% of the subjects with recorded BP value) (+ 13.3%,
      ci 12.5%-14.2%; p < 0.001 and + 7.3%, ci 6.7%-8.0%; p < 0.001). CONCLUSIONS:
      Almost 82% of hypertensive subjects who contact their doctors can be easily
      controlled. Most non-controlled patients simply don't see their GPs; in almost
      all the remaining non-controlled patients GPs fail to increase drug therapy. A
      further improvement is therefore possible.

PMID- 24330412
TI  - Evaluation of the Irritable Bowel Syndrome Quality of Life (IBS-QOL)
      questionnaire in diarrheal-predominant irritable bowel syndrome patients.
AB  - BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-d) significantly
      diminishes the health-related quality of life (HRQOL) of patients. Psychological
      and social impacts are common with many IBS-d patients reporting comorbid
      depression, anxiety, decreased intimacy, and lost working days. The Irritable
      Bowel Syndrome Quality of Life (IBS-QOL) questionnaire is a 34-item instrument
      developed and validated for measurement of HRQOL in non-subtyped IBS patients.
      The current paper assesses this previously-validated instrument employing data
      collected from 754 patients who participated in a randomized clinical trial of a
      novel treatment, eluxadoline, for IBS-d. METHODS: Psychometric methods common to
      HRQOL research were employed to evaluate the IBS-QOL. Many of the historical
      analyses of the IBS-QOL validations were used. Other techniques that extended the
      original methods were applied where more appropriate for the current dataset. In
      IBS-d patients, we analyzed the items and substructure of the IBS-QOL via item
      reduction, factor structure, internal consistency, reproducibility, construct
      validity, and ability to detect change. RESULTS: This study supports the IBS-QOL
      as a psychometrically valid measure. Factor analyses suggested that IBS-specific
      QOL as measured by the IBS-QOL is a unidimensional construct. Construct validity
      was further buttressed by significant correlations between IBS-QOL total scores
      and related measures of IBS-d severity including the historically-relevant
      Irritable Bowel Syndrome Adequate Relief (IBS-AR) item and the FDA's Clinical
      Responder definition. The IBS-QOL also showed a significant ability to detect
      change as evidenced by analysis of treatment effects. A minority of the items,
      unrelated to the IBS-d, performed less well by the standards set by the original
      authors. CONCLUSIONS: We established that the IBS-QOL total score is a
      psychometrically valid measure of HRQOL in IBS-d patients enrolled in this study.
      Our analyses suggest that the IBS-QOL items demonstrate very good construct
      validity and ability to detect changes due to treatment effects. Furthermore, our
      analyses suggest that the IBS-QOL items measure a univariate construct and we
      believe further modeling of the IBS-QOL from an item response theory (IRT)
      approach under both non-treatment and treatment conditions would greatly further
      our understanding as item-based methods could be used to develop a short form.

PMID- 24330413
TI  - Herbal medicine use in pregnancy: results of a multinational study.
AB  - BACKGROUND: The use of complementary and alternative medicines (CAM) is growing
      in the general population. Herbal medicines are used in all countries of the
      world and are included in the top CAM therapies used. METHODS: A multinational
      study on how women treat disease and pregnancy-related health ailments was
      conducted between October 2011 and February 2012 in Europe, North and South
      America and Australia. In this study, the primary aim was to determine the
      prevalence of herbal medicine use in pregnancy and factors related to such use
      across participating countries and regions. The secondary aim was to investigate
      who recommended the use of herbal medication in pregnancy. RESULTS: There were
      9,459 women from 23 countries participating in the study. Of these, 28.9%
      reported the use of herbal medicines in pregnancy. Most herbal medicines were
      used for pregnancy-related health ailments such as cold and nausea. Ginger,
      cranberry, valerian and raspberry were the most commonly used herbs in pregnancy.
      The highest reported rate of herbal use medicines was in Russia (69%). Women from
      Eastern Europe (51.8%) and Australia (43.8%) were twice as likely to use an
      herbal medicine versus other regions. Women using herbal medicines were
      characteristically having their first child, non-smokers, using folic acid and
      consuming some alcohol in pregnancy. Also, women who were currently students and
      women with an education other than a high school degree were more likely to use
      herbal medicines than other women. Although 1 out of 5 women stated that a
      physician had recommended the herbal use, most women used herbal medicine in
      pregnancy on their own initiative. CONCLUSIONS: In this multinational study
      herbal medicine use in pregnancy was high although there were distinct
      differences in the herbs and users of herbal medicines across regions. Most
      commonly the women self-medicated with herbal medicine to treat pregnancy-related
      health ailments. More knowledge regarding the efficacy and safety of herbal
      medicines in pregnancy is warranted.

PMID- 24330414
TI  - Beyond catalysis: vitamin B12 as a cofactor in gene regulation.
AB  - Vitamin B12 is well known as an enzyme cofactor in the catalysis of many
      important biological reactions, and the role of B12 in regulation of bacterial
      gene expression as a ligand of riboswitches is well established. Only recently
      evidence has emerged that B12 can also affect bacterial gene expression by acting
      as a cofactor of regulatory proteins. In 2011 a role of B12 as a cofactor of the
      transcriptional repressor of carotenogenesis, CarH, in Myxococcus xanthus was
      reported. B12 is required for light-dependent DNA binding by CarH, which can
      therefore be considered to be a new type of photoreceptor. Cheng et al. (2014)
      report the identification of B12 as a cofactor of the AerR protein in Rhodobacter
      capsulatus. AerR acts as an antirepressor of the CrtJ protein, which represses
      photosynthesis genes when binding to its target promoters. As in Myxococcus B12
      may have the role of a chromophore in photoreception, but it is suggested that a
      main function of AerR is the sensing of B12. The co-regulation of the pathways is
      beneficial because the syntheses of B12 , haem and bacteriochlorophylls share
      common precursors and the accumulation of the free molecules is toxic.

PMID- 24330415
TI  - Secukinumab improves the signs and symptoms of moderate-to-severe plaque
      psoriasis in subjects with involvement of hands and/or feet: subanalysis of a
      randomized, double-blind, placebo-controlled, phase 2 dose-ranging study.

PMID- 24330416
TI  - Great expectations? Pre-transplant quality of life expectations and distress
      after kidney transplantation: a prospective study.
AB  - OBJECTIVES: Previous research suggests that prior to kidney transplantation,
      patients overestimate their post-transplant quality of life (QoL). The current
      study aimed to corroborate these findings, identify determinants of QoL
      overestimation, examine its association with subsequent distress, and clarify the
      role of optimism. DESIGN: Prospective observational study. METHODS: Physical,
      psychological, and social QoL expectations, actual QoL, and distress (GHQ-12) of
      participants (56% male) were prospectively assessed before (T0; n = 228) and 3
      (T1; n = 149), 6 (T2; n = 146), and 12 (T3; n = 114) months after successful
      transplantation. RESULTS: Patients who were treated with haemodialysis before
      transplantation reported greater physical QoL overestimation than those who
      received treatment with peritoneal dialysis. Neither physical nor social QoL
      overestimation at T1 was prospectively associated with increased distress at T2
      or T3. The interaction between optimism and social QoL overestimation at T1 (beta
      = -.56, p < .001) for distress at T2 was significant, with patients low in
      optimism experiencing more distress after QoL overestimation. CONCLUSIONS: QoL
      overestimation is not associated with subsequent distress. Findings suggest that
      patients low in optimism are more vulnerable to distress following QoL
      overestimation. STATEMENT OF CONTRIBUTION: What is already known on this subject?
      Kidney transplantation improves patients' quality of life. Prior to kidney
      transplantation, patients overestimate the scale of this improvement. What does
      this study add? Quality of life overestimation is not associated with subsequent
      distress. When optimism is low, kidney transplant recipients experience higher
      distress following quality of life overestimation.

PMID- 24330417
TI  - Advance directives lessen the decisional burden of surrogate decision-making for
      the chronically critically ill.
AB  - AIMS AND OBJECTIVES: To identify the relationships between advance directive
      status, demographic characteristics and decisional burden (role stress and
      depressive symptoms) of surrogate decision-makers (SDMs) of patients with chronic
      critical illness. BACKGROUND: Although the prevalence of advance directives among
      Americans has increased, SDMs are ultimately responsible for complex medical
      decisions of the chronically critically ill patient. Decisional burden has
      lasting psychological effects on SDMs. There is insufficient evidence on the
      influence of advance directives on the decisional burden of surrogate decision
      makers of patients with chronic critical illness. DESIGN: The study was a
      secondary data analysis of cross-sectional data. Data were obtained from 489
      surrogate decision-makers of chronically critically ill patients at two academic
      medical centres in Northeast Ohio, United States, between September 2005-May
      2008. METHODS: Data were collected using demographic forms and questionnaires. A
      single-item measure of role stress and the Center for Epidemiological Studies
      Depression (CESD) scale were used to capture the SDM's decisional burden.
      Descriptive statistics, t-tests, chi-square and path analyses were performed.
      RESULTS: Surrogate decision-makers who were nonwhite, with low socioeconomic
      status and low education level were less likely to have advance directive
      documentation for their chronically critically ill patient. The presence of an
      advance directive mitigates the decisional burden by directly reducing the SDM's
      role stress and indirectly lessening the severity of depressive symptoms.
      CONCLUSIONS: Most SDMs of chronically critically ill patients will not have the
      benefit of knowing the patient's preferences for life-sustaining therapies and
      consequently be at risk of increased decisional burden. RELEVANCE TO CLINICAL
      PRACTICE: Study results are clinically useful for patient education on the
      influence of advance directives. Patients may be informed that SDMs without
      advance directives are at risk of increased decisional burden and will require
      decisional support to facilitate patient-centred decision-making.

PMID- 24330418
TI  - The use of 185 MBq and 740 MBq of 153-samarium hydroxyapatite for knee
      synovectomy in haemophilia.
AB  - The penetration of beta energy of 153-samarium ((153) Sm) (0.8 MeV) is not only
      appropriate for synovectomy of median articulations but is possible to improve
      the radiobiological effect using increased activities. The aim of this study was
      to assess the effectiveness of 185 MBq and 740 MBq of 153-samarium hydroxyapatite
      ((153) Sm-HA) in knees of haemophilic patients. Thirty-one patients--36 knees, 30
      males, were divided into two groups without coinjection of corticosteroid: A - 14
      patients (17 knees) treated with intra-articular dose of 185 MBq of (153) Sm-HA,
      average age 23 years; B--17 patients (19 knees) with 740 MBq of (153) Sm-HA,
      average age 21.3 years. The evaluation before and after 1 year of synovectomy
      used the following criteria: reduction in the number of haemarthroses and use of
      the coagulation factor and improvement in articular motility. Adverse-effects
      occurrence was considered too. Early and late scintigraphic studies were
      performed after synoviorthesis and no joint immobilization was recommended. The
      reduction in haemarthrosis and use of coagulation factor were: group 1--31.3% and
      25%; group 2--81.5% and 79% with P < 0.001 respectively; no significant
      improvement in knees motility was noted for both groups. Four cases of mild
      reactional synovitis were observed in each group. The scintigraphic control
      showed homogenous distribution of the radiopharmaceuticals with no articular
      escape; the material was considered safe by its permanence in the articulation.
      We have significant improvement in the synovectomy of haemophilic knees with 740
      MBq of (153) Sm-HA; the less penetration of its beta radiation was compensated by
      the increased biological effect with the higher used activity.

PMID- 24330419
TI  - One-year heterotopic cardiac xenograft survival in a pig to baboon model.

PMID- 24330421
TI  - The oxygen saturation in retinal vessels from diabetic patients depends on the
      severity and type of vision-threatening retinopathy.
AB  - PURPOSE: Diabetic retinopathy is characterized by morphological lesions in the
      retina secondary to disturbances in retinal blood flow which may influence the
      supply of oxygen to the retinal metabolism. Using retinal oximetry, it has been
      shown that the oxygen saturation is increased in retinal arterioles and venules
      from diabetic patients with retinopathy, but oxygenation before the development
      of retinopathy and possible differences in retinal oxygenation between diabetic
      maculopathy and proliferative diabetic retinopathy patients have not been
      evaluated. METHODS: One-hundred and fifty-six consecutive patients referred for
      specialist evaluation of diabetic retinopathy, and eighty normal control persons
      were subjected to retinal oximetry of the larger retinal arterioles and venules.
      The diabetic patients were allocated to one of four groups with severity of
      retinopathy ranging from no retinopathy to vision-threatening retinopathy, and
      the oxygen saturation in arterioles and venules was compared between these
      groups. RESULTS: Increasing severity of retinal changes from no retinopathy to
      diabetic maculopathy was accompanied with increasing oxygen saturation in retinal
      venules and decreasing oxygen extraction, whereas proliferative diabetic
      retinopathy showed increased oxygen saturation in both retinal arterioles and
      venules to result in a normal oxygen extraction. CONCLUSION: Prospective
      observational and interventional studies are needed to show whether changes in
      retinal oxygen saturation precede or follow the development of diabetic
      retinopathy. Additionally, studies of regional variations in haemodynamic
      parameters in patients with vision-threatening diabetic retinopathy might improve
      the understanding of the pathophysiology of diabetic retinopathy. This is a
      precondition for improving the prevention and treatment of the disease.

PMID- 24330422
TI  - Impact of vitamin A with zinc supplementation on malaria morbidity in Ghana.
AB  - BACKGROUND: Malaria is a leading cause of morbidity and mortality among young
      children and is estimated to cause at least 1 million deaths each year especially
      among pregnant women and young children under the age of five years. Vitamin A
      supplementation is known to reduce morbidity and mortality in young children.
      Zinc is required for growth and immunity and we sought to replicate the study by
      Zeba et al. which showed 30% lower cases of clinical malaria in children on a
      combination of zinc and a large dose of vitamin A compared with children on
      vitamin A alone based on the hypothesis that combined vitamin A and zinc reduced
      symptomatic malaria compared to vitamin A alone. OBJECTIVES: The primary
      objective was to determine the effect of vitamin A alone vs. vitamin A and zinc
      supplements on the incidence of clinical malaria and other anthropometric
      indices. It also sought to assess the effects on the incidence of anaemia,
      diarrhoea and pneumonia. METHODS: The study was community-based and 200 children
      between the ages of 6-24 months were randomised to receive either vitamin A
      (100,000 IU for infants less than 12 months & 200,000 IU for children greater
      than 12 months and 10 mg daily zinc in the intervention group or vitamin A and
      zinc placebo for 6 months in the control group. RESULTS: The number of children
      who were diagnosed with uncomplicated malaria in the intervention group was 27%
      significantly lower compared with the children in the control group (p = 0.03).
      There were, however, no effects on severe malaria, pneumonia, anaemia and
      diarrhea. CONCLUSIONS: Our study confirms a significant role of vitamin A and
      zinc in reducing malaria morbidity.

PMID- 24330423
TI  - Loss of Raf-1 kinase inhibitor protein (RKIP) is strongly associated with high
      grade tumor budding and correlates with an aggressive phenotype in pancreatic
      ductal adenocarcinoma (PDAC).
AB  - BACKGROUND: Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant
      metastatic suppressor in a variety of human cancers and is known to inhibit
      Ras/Raf/MEK/ERK signaling. By suppressing the activation of the NFkB/SNAIL
      circuit, RKIP can regulate the induction of epithelial-mesenchymal transition
      (EMT). The aim of this study was to evaluate RKIP expression and to determine its
      association with clinicopathological features, including EMT in form of tumor
      budding in pancreatic ductal adenocarcinoma (PDAC). METHODS: Staining for RKIP
      was performed on a multipunch Tissue Microarray (TMA) of 114 well-characterized
      PDACs with clinico-pathological, follow-up and adjuvant therapy information. RKIP
      expression was assessed separately in the main tumor body and in the tumor buds.
      Another 3 TMAs containing normal pancreatic tissue, precursor lesions (Pancreatic
      Intraepithelial Neoplasia, PanINs) and matched lymph node metastases were stained
      in parallel. Cut-off values were calculated by receiver operating characteristic
      (ROC) curve analysis. RESULTS: We found a significant progressive loss of RKIP
      expression between normal pancreatic ductal epithelia (average: 74%), precursor
      lesions (PanINs; average: 37%), PDAC (average 20%) and lymph node metastases
      (average 8%, p<0.0001). RKIP expression was significantly lower in tumor buds
      (average: 6%) compared to the main tumor body (average 20%; p<0.005). RKIP loss
      in the tumor body was marginally associated with advanced T-stage (p=0.0599) as
      well as high-grade peritumoral (p=0.0048) and intratumoral budding (p=0.0373).
      RKIP loss in the buds showed a clear association with advanced T stage
      (p=0.0089). CONCLUSIONS: The progressive loss of RKIP seems to play a major role
      in the neoplastic transformation of pancreas, correlates with aggressive features
      in PDAC and is associated with the presence of EMT in form of tumor budding.

PMID- 24330424
TI  - Molecular analysis and distribution of multidrug-resistant Enterococcus faecium
      isolates belonging to clonal complex 17 in a tertiary care center in Mexico City.
AB  - BACKGROUND: Enterococcus faecium has recently emerged as a multidrug-resistant
      nosocomial pathogen involved in outbreaks worldwide. A high rate of resistance to
      different antibiotics has been associated with virulent clonal complex 17
      isolates carrying the esp and hyl genes and the purK1 allele. RESULTS: Twelve
      clinical vancomycin-resistant Enterococcus faecium (VREF) isolates were obtained
      from pediatric patients at the Hospital Infantil de Mexico Federico Gomez
      (HIMFG). Among these VREF isolates, 58.3% (7/12) were recovered from urine, while
      41.7% (5/12) were recovered from the bloodstream. The VREF isolates showed a 100%
      rate of resistance to ampicillin, amoxicillin-clavulanate, ciprofloxacin,
      clindamycin, chloramphenicol, streptomycin, gentamicin, rifampicin, erythromycin
      and teicoplanin. In addition, 16.7% (2/12) of the isolates were resistant to
      linezolid, and 66.7% (8/12) were resistant to tetracycline and doxycycline. PCR
      analysis revealed the presence of the vanA gene in all 12 VREF isolates, esp in
      83.3% (10/12) of the isolates and hyl in 50% (6/12) of the isolates. Phylogenetic
      analysis via molecular typing was performed using pulsed-field gel
      electrophoresis (PFGE) and demonstrated 44% similarity among the VREF isolates.
      MLST analysis identified four different sequence types (ST412, ST757, ST203 and
      ST612). CONCLUSION: This study provides the first report of multidrug-resistant
      VREF isolates belonging to clonal complex 17 from a tertiary care center in
      Mexico City. Multidrug resistance and genetic determinants of virulence confer
      advantages among VREF in the colonization of their host. Therefore, the
      prevention and control of the spread of nosocomial infections caused by VREF is
      crucial for identifying new emergent subclones that could be challenging to treat
      in subsequent years.

PMID- 24330425
TI  - Health promotion in the Danish maritime setting: challenges and possibilities for
      changing lifestyle behavior and health among seafarers.
AB  - BACKGROUND: Seafaring is a risky occupation when compared to land-based
      industries as incidence rates of mortality and morbidity are higher. This trend
      is partly due to a higher number of accidents but also higher incidence of
      lifestyle-related diseases like cardiovascular disease and lung cancer. In
      Denmark, the proportion of smokers as well as of overweight and obese persons is
      higher among seafarers compared to the general population. This high burden of
      risk indicates that this occupational group might be a growing challenge at sea
      in regard to safety and health issues and there is a need to further our
      understanding of the health promotion approaches that work. METHODS: A single
      group pre-post design was conducted in 2008-2009 in order to identify changes in
      lifestyle related behaviors and health risk factors among seafarers (N: 606) in
      two Danish shipping companies after implementing two structural health promotion
      interventions (healthy cooking courses for ship cooks and improvement of fitness
      facilities) as well as health education interventions (smoking cessation courses,
      individual exercise guidance and extra health check-ups) at the maritime
      workplace. Baseline and follow-up data were collected with a self-administrated
      standardized questionnaire and individual health profiling assessing parameters
      such as physical health and physical fitness. In addition, qualitative interviews
      with participants and non-participants were conducted in order to gain in-depth
      information on experiences with the intervention processes. RESULTS: Significant
      changes were identified for levels of fitness, daily sugar intake and metabolic
      syndrome. However, these results were not associated with participating in the
      health educational interventions. One possible explanation for the improved
      fitness rate could be the upgrading of fitness equipment onboard the ships
      provided by the management level. The decrease in daily sugar intake and
      prevalence of seafarers with metabolic syndrome might be associated with the
      cooking course intervention which aimed at providing healthier daily meals on
      board. CONCLUSION: The findings suggest that a multicomponent health promotion
      intervention program has the potential to achieve change in seafarers' health
      behavior and health parameters. In the future, studies with more rigorous
      designs, separately testing the contribution of different types of interventions
      are needed.

PMID- 24330426
TI  - Gender dependence of serum soluble Klotho in acromegaly.
AB  - OBJECTIVES: In acromegaly, disease activity is biochemically assessed by growth
      hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. However, they are
      often discrepant, as several factors including gender influence their
      relationship. We recently found excessively high serum levels of soluble Klotho
      (sKl) in acromegalic patients, which depended on GH to a comparable extent as IGF
      1. To further elucidate the relationship between GH and sKl, we examined the
      effect of gender on sKl in patients with untreated acromegaly. PATIENTS AND
      DESIGN: We determined GH, IGF-1 and sKl in sera of 62 consecutive patients with
      newly diagnosed acromegaly (31 females/31 males, aged 20-85 years). RESULTS: For
      their given GH excess at presentation with acromegaly, females had lower IGF-1
      (490 +/- 33 vs 604 +/- 33 ng/ml, P = 0.02), but higher sKl [5171 +/- 590 vs 3439
      +/- 431 pg/ml (mean +/- SE), P = 0.02] levels than males. In multiple regression
      analysis, IGF-1 was closely associated with logGH (estimate 139, SE 47, P =
      0.005) and BMI (estimate 14.2, SE 4.8, P = 0.005). sKl was closely associated
      with logGH (estimate 3088, SE 652, P = 0.0001) and gender (estimate 2034, SE 612,
      P = 0.002), and to a lesser extent with BMI (estimate 174, SE 66, P = 0.01).
      CONCLUSIONS: For a given GH status, sKl concentrations are higher and IGF-1
      concentrations are lower in women than in men. GH is the strongest predictor for
      both sKl and IGF-1, but gender needs to be considered when using these parameters
      for monitoring acromegalic patients.

PMID- 24330427
TI  - The effect of cognitive reappraisal on long-term emotional experience and
      emotional memory.
AB  - One's ability to properly regulate emotion is critical to psychological and
      physical well-being. Among various strategies to regulate emotion, cognitive
      reappraisal has been shown to modulate both emotional experience and emotional
      memory. However, most studies of reappraisal have focused on reappraisal of
      negative situations, with reappraisal of positive emotion receiving considerably
      less attention. In addition, the effects of reappraisal on emotional reactions to
      stimuli are typically only assessed either immediately or after a short delay,
      and it remains unclear whether reappraisal effects persist over longer time
      periods. We investigated the effect of cognitive reappraisal on emotional
      reactions and long-term episodic memory for positive and negative stimuli. Men
      and women viewed emotionally negative, positive, and neutral pictures while they
      were instructed to either increase, decrease, or maintain the initial emotional
      reactions elicited by the pictures. Subjective ratings of emotional valence and
      arousal were assessed during the regulation task and again after 1 week. Memory
      for the pictures was assessed with free recall. Results indicated that pictures
      accompanied by instructions to increase emotion were better recalled than
      pictures reappraised to decrease emotion. Modulation of emotional arousal
      elicited by stimuli persisted over a week, but this effect was observed only for
      men. These findings suggest that cognitive reappraisal can have long-lasting
      effects on emotional reactions to stimuli. However, the sex differences observed
      for the effects of reappraisal on emotional reactions highlight the importance of
      considering individual differences in the effects of regulation.

PMID- 24330428
TI  - Using passenger mutations to estimate the timing of driver mutations and identify
      mutator alterations.
AB  - BACKGROUND: Recent developments in high-throughput genomic technologies make it
      possible to have a comprehensive view of genomic alterations in tumors on a whole
      genome scale. Only a small number of somatic alterations detected in tumor
      genomes are driver alterations which drive tumorigenesis. Most of the somatic
      alterations are passengers that are neutral to tumor cell selection. Although
      most research efforts are focused on analyzing driver alterations, the passenger
      alterations also provide valuable information about the history of tumor
      development. RESULTS: In this paper, we develop a method for estimating the age
      of the tumor lineage and the timing of the driver alterations based on the number
      of passenger alterations. This method also identifies mutator genes which
      increase genomic instability when they are altered and provides estimates of the
      increased rate of alterations caused by each mutator gene. We applied this method
      to copy number data and DNA sequencing data for ovarian and lung tumors. We
      identified well known mutators such as TP53, PRKDC, BRCA1/2 as well as new
      mutator candidates PPP2R2A and the chromosomal region 22q13.33. We found that
      most mutator genes alter early during tumorigenesis and were able to estimate the
      age of individual tumor lineage in cell generations. CONCLUSIONS: This is the
      first computational method to identify mutator genes and to take into account the
      increase of the alteration rate by mutator genes, providing more accurate
      estimates of the tumor age and the timing of driver alterations.

PMID- 24330429
TI  - Anxiety symptoms and coping strategies in the perinatal period.
AB  - BACKGROUND: The aim of the present study was to explore the prospective
      relationship between anxiety symptoms and coping strategies during late pregnancy
      and early postpartum. METHODS: Participants completed the Hospital Anxiety
      Depression-Anxiety subscale and Carver's Brief COPE at two time points, namely
      during the last trimester of pregnancy (N = 400) and at two months postpartum (N
      = 158). RESULTS: Antenatally, 18.8% of pregnant women presented severe anxiety
      symptoms while 20.2% of women presented severe anxiety symptoms after birth.
      Carver's proposed coping styles allowed to significantly distinguish between
      anxious and non anxious women during these two periods. Anxious women used
      significantly more inappropriate coping and less adaptive coping responses, such
      as self-blame and denial of reality, which remained associated with anxiety in
      the perinatal period. Our results also indicated a decrease in adaptive coping in
      women without anxiety after birth (e.g. acceptance, positive reframing).
      CONCLUSION: Our findings confirm that antenatal and postnatal anxiety symptoms
      occur frequently and that inappropriate and/or non functional coping may account
      for persisting anxiety after childbirth. LIMITATIONS: Data were based on self
      reports and participating women were predominantly primiparous. A high drop-out
      rate at two months postpartum must also be acknowledged.

PMID- 24330430
TI  - Consumption of medical resources and outcome of shoulder disorders in primary
      health care consulters.
AB  - BACKGROUND: Shoulder disorders are common problems in primary health care. The
      course of disease of patients consulting for a new episode of a shoulder problem
      has been thought to be benign. In this prospective cohort study, we assessed the
      one-year consumption of medical resources and clinical outcome of shoulder
      disorders inclusive of all disease episodes. METHODS: All individuals consulting
      primary health care for shoulder disorder in a catchment area of more than 120
      000 people were included. A composite questionnaire including the American
      Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) was used
      to measure use of resources as well as shoulder pain and function. A follow-up
      assessment was performed after one year. RESULTS: A total of 128 individuals
      responded to the questionnaire. Only 24% of the patients had recovered after one
      year. Mean shoulder pain (Visual analogue scale, VAS, max 100 mm) decreased from
      38.9 mm to 28.6 mm (95% CI -16.3 to -4.2 mm). The ASES score (max 100) improved
      significantly from 59.9 to 70.2 (95% CI 5.3 to 15.3). Mean one-year consumption
      of medical resources after the index consultation was 1.5 consultations, 0.5
      radiological examinations, and 3.3 visits to physiotherapist. Mean resource
      weighted direct costs were ?543/patient/year (95% CI ?351 to 735). CONCLUSIONS:
      Shoulder disorders are often chronic and require a significant amount of
      resources from the health care system. The clinical outcome of the management of
      shoulder disorders in our study population including also individuals who have
      consulted previously for a shoulder problem is notably poorer than the one
      reported by previous studies on new episodes. However, despite the relatively
      modest outcome, subjective disability is low.

PMID- 24330432
TI  - Systematic review and meta-analysis of published trials comparing the
      effectiveness of transanal endoscopic microsurgery and radical resection in the
      management of early rectal cancer.
AB  - AIM: A systematic analysis was conducted of trials comparing the effectiveness of
      transanal endoscopic microsurgery (TEMS) with radical resection (RR) for T1 and
      T2 rectal cancer. METHOD: An electronic search was carried out of trials
      reporting the effectiveness of TEMS and RR in the treatment of T1 and T2 rectal
      cancers. RESULTS: Ten trials including 942 patients were retrieved. There was a
      trend toward a higher risk of local recurrence (odds ratio 2.78; 95% confidence
      interval 1.42, 5.44; z = 2.97; P < 0.003) and overall recurrence (P < 0.01)
      following TEMS compared with RR. The risk of distant recurrence, overall survival
      (odds ratio 0.90; 95% confidence interval 0.49, 1.66; z = 0.33; P = 0.74) and
      mortality was similar. TEMS was associated with a shorter operation time and
      hospital stay and a reduced risk of postoperative complications (P < 0.0001). The
      included studies, however, were significantly diverse in stage and grade of
      rectal cancer and the use of neoadjuvant chemoradiotherapy. CONCLUSION: Transanal
      endoscopic microsurgery appears to have clinically measurable advantages in
      patients with early rectal cancer. The studies included in this review do not
      allow firm conclusions as to whether TEMS is superior to RR in the management of
      early rectal cancer. Larger, better designed and executed prospective studies are
      needed to answer this question.

PMID- 24330433
TI  - Commentary on Sajid et al.

PMID- 24330434
TI  - Commentary on Young et al.

PMID- 24330435
TI  - Reply to Beaton et al.

PMID- 24330440
TI  - First report: Robotic pelvic exenteration for locally advanced rectal cancer.
AB  - AIM: The aim of this study was to present the feasibility and surgical outcome of
      robotic en bloc resection of the rectum and with prostate and seminal vesicle
      invaded by rectal cancer. METHOD: The details of three consecutive cases
      involving male patients in their forties, with locally invasive low rectal
      cancers are presented. The da Vinci robotic system was used by experienced
      colorectal and urological surgeons to perform en bloc resection of the rectum,
      prostate and seminal vesicles. RESULTS: In the first case, coloanal and vesico
      urethral anastomoses were performed, and the second included an end colostomy and
      vesico-urethral anastomosis. The bladder and bulbar urethra were also removed en
      bloc in the third case, with robotic intracorporeal ileal conduit formation and
      end colostomy. There was no major complication postoperatively. In the second
      patient there was a minor leakage at the vesico-urethral anastomosis. The third
      was readmitted the following week with a urinary infection which settled with
      intravenous antibiotics. In the first case, the circumferential resection margin
      was microscopically positive but the patient is currently free of recurrence
      after 14 months. In the second and third cases, all margins were clear.
      CONCLUSION: This the first report of the use of the da Vinci robotic system for
      pelvic exenteration in patients with locally advanced rectal cancer invading the
      prostate and seminal vesicles. The robot may have a potential role in selected
      patients requiring exenterative pelvic surgery particularly in men.

PMID- 24330441
TI  - Early events and lifelong change: looking beyond survival in the very young.

PMID- 24330442
TI  - Do we actually need to anesthetize the neonate?

PMID- 24330443
TI  - Limitations and vulnerabilities of the neonatal cardiovascular system:
      considerations for anesthetic management.
AB  - Development of the cardiovascular system through the last trimester of pregnancy
      and the subsequent neonatal period is profound. Morphological changes within the
      myocardium make the heart vulnerable to challenges such as fluid shifts and
      anesthetic drugs. The sensitivity of the myocardium to metabolic challenges and
      potential harm of drugs needed to maintain adequate blood pressure and cardiac
      output are highlighted. Traditional monitoring under anesthesia has focussed on
      maintaining oxygenation and heart rate in the neonate with less attention paid to
      blood pressure, cardiac output, and more importantly organ well-being. There is
      now a better understanding of the limitations of blood pressure homeostasis in
      the neonate and the potential consequences of marginal hypoperfusion. This
      article highlights some of these vulnerabilities particularly as they relate to
      anesthesia and surgery in the very young. 

PMID- 24330447
TI  - Antifungal and antibacterial activity and chemical composition of polar and non
      polar extracts of Athrixia phylicoides determined using bioautography and HPLC.
AB  - BACKGROUND: Athrixia phylicoides DC. (Asteraceae) is used medicinally in South
      Africa to treat a plethora of ailments, including heart problems, diabetes,
      diarrhoea, sores and infected wounds. It is also prepared in the form of a tea
      (hot decoction) taken as a refreshing, pleasant-tasting beverage with
      commercialization potential. METHODS: Extracts of the dried ground aerial parts
      were prepared using organic solvents (diethyl ether, dichloromethane/methanol,
      ethyl acetate and ethanol) and water. These extracts were subjected to HPLC, TLC
      and bioautography analysis with the aim of linking a range of peaks visualized in
      HPLC chromatography profiles to antibacterial and antifungal activity of the same
      extracts. RESULTS: HPLC revealed a group of compounds extracted by more than one
      solvent. Compounds identified include inositol, caffeic acid, quercetin,
      kaempferol, apigenin, hymenoxin and oleanolic acid. The organic extracts
      displayed similar TLC profiles, and bioautography indicated approximately five
      antibacterial compounds, but only two antifungal compounds in these extracts.
      Bioautography indicated that cold water extracted the least antimicrobial
      compounds. CONCLUSIONS: Several previously unknown compounds were identified in
      Athrixia phylicoides extracts, and bioautography indicated a number of
      antibacterial and antifungal compounds. There were notable differences in
      chemical composition and bioactivity between the organic and aqueous extracts.
      Further research is necessary to fully characterize the active components of the
      extracts.

PMID- 24330445
TI  - Anesthesia and long-term outcomes after neonatal intensive care.
AB  - As survival is now increasing, care of the extremely preterm infant is now
      directed at strategies to minimize long-term morbidity. In this study, I review
      the current state-of-the-art outcomes for babies born at extremely low gestations
      and identify strategies that may be aimed at optimizing outcomes. With respect to
      anesthetic practice, I then go on to discuss important issues of pain management
      in these babies and how this may affect long-term outcomes. 

PMID- 24330446
TI  - Ceramides predict verbal memory performance in coronary artery disease patients
      undertaking exercise: a prospective cohort pilot study.
AB  - BACKGROUND: Coronary artery disease (CAD) is associated with verbal memory
      decline, although deterioration may be mitigated in individuals undertaking
      exercise interventions. Ceramide sphingolipids, suggested to play a role in
      pathological neurodegeneration, have been associated with the development and
      progression of CAD but their relationship with cognitive response to exercise has
      not been assessed. In this study, concentrations of very long chain ceramides
      (C22:0 and C24:0) were assessed as predictors of changes in verbal memory
      performance over 1 year in subjects with CAD undertaking cardiac rehabilitation
      (CR). METHODS: Verbal memory was measured using the California Verbal Learning
      Test 2nd Ed. (CVLT-II), from which Z-scores were calculated based on age, gender
      and education matched norms. Baseline plasma C22:0 and C24:0 ceramide
      concentrations were measured from fasting blood samples using high performance
      liquid chromatography coupled electrospray ionization tandem mass spectrometry
      (LC/MS/MS). Repeated measures general linear models were used to determine the
      association between baseline plasma ceramides and the change in verbal memory
      performance over 1 year of CR controlling for age and body mass index (BMI).
      RESULTS: In patients with CAD (n = 33, mean age = 62 +/- 9 years, 84.8% male,
      years of education = 17 +/- 3 years), higher baseline plasma C22:0 (F1, 29 =
      5.30, p = 0.03) and C24:0 (F1, 29 = 4.04, p = 0.05) concentrations significantly
      predicted less improvement in verbal memory performance over 1 year of CR
      controlling for age and BMI. CONCLUSIONS: Plasma ceramide concentrations should
      be further examined as potential predictors of cognitive response to exercise and
      worse cognitive outcomes in patients with CAD.

PMID- 24330448
TI  - Improving performance under mirror-image conditions during laparoscopic surgery
      using the Broadview camera system.
AB  - INTRODUCTION: Under mirror-image conditions, surgeons often become confused and
      their task performance may deteriorate. This study aimed to quantitatively
      investigate the difficulty of performing laparoscopic surgery based on a mirror
      image and to find methods to improve performance under these conditions. METHODS:
      Twelve medical students with no prior endoscopic surgical experience and 10
      surgical residents, each with over 50 laparoscopic surgery experiences,
      participated in this study. Three measures were assessed using the Hiroshima
      University Endoscopic Surgical Assessment Device: the deviation with integrated
      time, the approaching time, and the peak velocity. The scope was placed at 0
      degrees  (coaxial position), 180 degrees  (mirror-image condition), and 180
      degrees  using the Broadview camera system. Each participant performed the
      Hiroshima University Endoscopic Surgical Assessment Device task 10 times.
      RESULTS: The deviation with integrated time, the approaching time, and the peak
      velocity were better for surgical residents than for novices at 0 degrees  (P <
      0.001, P = 0.001, P = 0.011). The deviation with integrated time, the approaching
      time, and the peak velocity at 180 degrees  were significantly worse than the
      corresponding values at 0 degrees  (P < 0.0001) for both surgical residents and
      novices. All three types of Hiroshima University Endoscopic Surgical Assessment
      Device assessment at 180 degrees  were significantly better when the Broadview
      camera system was used than when it was not (P < 0.0001). CONCLUSION: This study
      showed quantitatively the difficulty in manipulating laparoscopic instruments in
      mirror-image conditions. Using the Broadview camera system improved surgeons'
      performance under mirror-image conditions during laparoscopic surgery.

PMID- 24330444
TI  - Neonatal pain.
AB  - Effective management of procedural and postoperative pain in neonates is required
      to minimize acute physiological and behavioral distress and may also improve
      acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from
      the periphery to the cortex, in neonates and behavioral responses form the basis
      for validated pain assessment tools. However, there is an increasing awareness of
      the need to not only reduce acute behavioral responses to pain in neonates, but
      also to protect the developing nervous system from persistent sensitization of
      pain pathways and potential damaging effects of altered neural activity on
      central nervous system development. Analgesic requirements are influenced by age
      related changes in both pharmacokinetic and pharmacodynamic response, and
      increasing data are available to guide safe and effective dosing with opioids and
      paracetamol. Regional analgesic techniques provide effective perioperative
      analgesia, but higher complication rates in neonates emphasize the importance of
      monitoring and choice of the most appropriate drug and dose. There have been
      significant improvements in the understanding and management of neonatal pain,
      but additional research evidence will further reduce the need to extrapolate data
      from older age groups. Translation into improved clinical care will continue to
      depend on an integrated approach to implementation that encompasses assessment
      and titration against individual response, education and training, and audit and
      feedback. 

PMID- 24330449
TI  - Efficacy of transversus abdominis plane block for acute postoperative pain relief
      in kidney recipients: a double-blinded clinical trial.
AB  - BACKGROUND: After renal transplantation, postoperative pain is usually mild to
      moderate. Postoperative pain is a concern and administration of systemic
      analgesic may be difficult because of underlying co-morbidities and variable
      responses of the graft. The transversus abdominis plane (TAP) block is one of the
      different approaches for postoperative pain relief following abdominal surgeries.
      We evaluated analgesic efficacy of TAP block on early postoperative pain by
      numeric rating scale (NRS) and morphine consumption during the first 24 hours
      after kidney transplantation. METHODS: Forty-four patients, scheduled as kidney
      recipients were randomized into two equal groups and were anesthetized with the
      same technique. After the induction of anesthesia, 15 mL of 0.25% Bupivacaine
      plus 5 MU/ml epinephrine or saline was deposited into the transversus abdominis
      neuro-fascial plane on the side of surgery by ultrasound guide. Each patient was
      assessed by a blinded investigator using NRS at 1st, 4th, 8th, 12th, and 24th
      hour postoperatively. RESULTS: Demographic data were not significantly different
      between the study groups. There was significant difference in median of NRS score
      measured at all time points in the study groups (P < 0.001). The 24-hour morphine
      consumption (mean +/- SD) was 10.8 +/- 9.5 mg in bupivacaine group compared with
      41.2 +/- 3.8 mg in the saline group (P = 0.001). There was statistically
      significant reduction in intraoperative fentanyl consumption in the TAP group 120
      +/- 20 MUg compared to the control group 358 +/- 24 MUg (P = 0.001). In study
      group 4 patients and in control group 90 patients received morphine titration for
      pain relief (P = 0.03). There was no complication in the study groups related to
      nerve block. Only two patients in saline group had nausea (P = 0.07). None of our
      patients received any other oral or IV rescue medication. CONCLUSION: Ultrasound
      TAP block can reduce postrenal transplantation pain and the amount of opioids
      consumption intraoperatively and during the first 24 hours after surgery in
      kidney recipients.

PMID- 24330450
TI  - DISCOVER trial- Distal resection of the pancreas with or without coverage of the
      pancreatic remnant: study protocol of a randomised controlled trial.
AB  - BACKGROUND: Distal pancreatectomy for benign and malignant tumours is the second
      most common surgical procedure on the pancreas. Postoperative pancreatic fistulas
      (POPF) represent the most significant clinical complication, causing prolongation
      of hospital stay and the need for additional diagnostic and therapeutic
      procedures. Although various techniques for preventing POPF have been evaluated,
      to date, there is no available technique that ensures closure of the pancreatic
      remnant. METHODS/DESIGN: DISCOVER will aim to investigate differences in the
      postoperative course after a distal pancreatectomy comparing the standard
      surgical technique with an alternative technique that provides additional
      coverage of the pancreatic remnant by the falciform ligament. The primary
      endpoint of this trial will be the rate of POPF. As secondary endpoints,
      incidence of postoperative morbidity and mortality, length of hospital stay, and
      quality of life will be assessed.DISCOVER is a single-centre, randomised,
      controlled surgical trial. For statistical analysis, a binary logistic regression
      model will be used. With a level of significance of 5% and a power of 80%, a
      sample size of 75 patients per group has been identified as necessary.
      DISCUSSION: The findings of this trial will help to evaluate the usefulness of
      the coverage procedure at reducing the rate of POPF. The results could influence
      the standard procedure for remnant closure after distal pancreatectomy. TRIAL
      REGISTRATION: Clinical trials register (DRKS-ID: DRKS00000546).

PMID- 24330452
TI  - Socially flexible female choice and premating isolation in field crickets
      (Teleogryllus spp.).
AB  - Social influences on mate choice are predicted to influence evolutionary
      divergence of closely related taxa, because of the key role mate choice plays in
      reproductive isolation. However, it is unclear whether females choosing between
      heterospecific and conspecific male signals use previously experienced social
      information in the same manner or to the same extent that they do when
      discriminating among conspecific mates only. We tested this using two field
      cricket sister species (Teleogryllus oceanicus and Teleogryllus commodus), in
      which considerable information is known about the role of male calling song in
      premating isolation, in addition to the influence of acoustic experience on the
      development of reproductive traits. We manipulated the acoustic experience of
      replicate populations of both species and found, unexpectedly, that experience of
      male calling song during rearing did not change how accurate females were in
      choosing a conspecific over a heterospecific male song during playback trials.
      However, females with acoustic experience were considerably less responsive to
      male song compared with naive females. Our results suggest that variation in the
      acoustic environment affects mate choice in both species, but that it may have a
      limited impact on premating isolation. The fact that social flexibility during
      interspecific mate discrimination does not appear to operate identically to that
      which occurs during conspecific mate discrimination highlights the importance of
      considering the context in which animals exercise socially flexible mating
      behaviours. We suggest an explanation for why social flexibility might be context
      dependent and discuss the consequences of such flexibility for the evolution of
      reproductive isolation. 

PMID- 24330451
TI  - Analysis of 20alpha-hydroxysteroid dehydrogenase expression in the corpus luteum
      of the buffalo cow: effect of prostaglandin F2-alpha treatment on circulating
      20alpha-hydroxyprogesterone levels.
AB  - BACKGROUND: During female reproductive cycles, a rapid fall in circulating
      progesterone (P4) levels is one of the earliest events that occur during induced
      luteolysis in mammals. In rodents, it is well recognized that during luteolysis,
      P4 is catabolized to its inactive metabolite, 20alpha-hydroxyprogesterone
      (20alpha-OHP) by the action of 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD)
      enzyme and involves transcription factor, Nur77. Studies have been carried out to
      examine expression of 20alpha-HSD and its activity in the corpus luteum (CL) of
      buffalo cow. METHODS: The expression of 20alpha-HSD across different bovine
      tissues along with CL was examined by qPCR analysis. Circulating P4 levels were
      monitored before and during PGF2alpha treatment. Expression of 20alpha-HSD and
      Nur77 mRNA was determined in CL at different time points post PGF2alpha treatment
      in buffalo cows. The chromatographic separation of P4 and its metabolite, 20alpha
      OHP, in rat and buffalo cow serum samples were performed on reverse phase HPLC
      system. To further support the findings, 20alpha-HSD enzyme activity was
      quantitated in cytosolic fraction of CL of both rat and buffalo cow. RESULTS:
      Circulating P4 concentration declined rapidly in response to PGF2alpha treatment.
      HPLC analysis of serum samples did not reveal changes in circulating 20alpha-OHP
      levels in buffalo cows but serum from pseudo pregnant rats receiving PGF2alpha
      treatment showed an increased 20alpha-OHP level at 24 h post treatment with
      accompanying decrease in P4 concentration. qPCR expression of 20alpha-HSD in CL
      from control and PGF2alpha-treated buffalo cows showed higher expression at 3 and
      18 h post treatment, but its specific activity was not altered at different time
      points post PGF2alpha treatment. The Nur77 expression increased several fold 3 h
      post PGF2alpha treatment similar to the increased expression observed in the
      PGF2alpha-treated pseudo pregnant rats which perhaps suggest initiation of
      activation of apoptotic pathways in response to PGF2alpha treatment. CONCLUSIONS:
      The results taken together suggest that synthesis of P4 appears to be primarily
      affected by PGF2alpha treatment in buffalo cows in contrast to increased
      metabolism of P4 in rodents.

PMID- 24330453
TI  - Strategies for recreating normal life: Iranian coronary heart disease patients'
      perspectives on coping strategies.
AB  - AIMS AND OBJECTIVES: To identify coping strategies used by Iranian patients with
      coronary heart disease. BACKGROUND: One of the most important nursing
      interventions is facilitating adjustment for patients. A deeper understanding of
      patients' coping strategies for controlling illness and its consequences is
      needed. DESIGN: A qualitative design. METHODS: Participants were hospitalised
      patients diagnosed with coronary heart disease, based on documented angiographic
      results. A qualitative study using semi-structured interviews was conducted, and
      purposive sampling was performed. The qualitative content analysis determined
      categories and subcategories for describing and understanding coping strategies.
      RESULTS: The term 'coping strategies' refers to the strategies used by
      participants living with coronary heart disease as they attempt to understand and
      control their chronic condition and return to a social and physical state as
      similar to their predisease condition as possible. During the data analysis, six
      strategies emerged: searching for meaning and information; trying to achieve
      comfort and control; resting more, doing less and slowing down; motivating,
      prioritising and caring for self; turning to religion and spirituality; and
      expectations and receiving assistance and support. CONCLUSIONS: This qualitative
      study describes the coping strategies of Iranian patients with coronary heart
      disease and the commonalities with strategies for others dealing with chronic
      illnesses in Iran. The patients were found to use a variety of coping strategies
      to deal with their illness and its impacts on their lives. RELEVANCE TO CLINICAL
      PRACTICE: This study contributes to the existing body of knowledge about optimal
      nursing care strategies for patients with coronary heart disease. Through
      increasing awareness of coping strategies, nurses can help their patients employ
      the most effective tools and reinforce constructive successful coping styles for
      patients who are dealing with coronary heart disease.

PMID- 24330455
TI  - Ex vivo normothermic perfusion of declined human kidneys after inadequate in situ
      perfusion.

PMID- 24330454
TI  - The metabolic signature associated with the Western dietary pattern: a cross
      sectional study.
AB  - BACKGROUND: Metabolic profiles have been shown to be associated to obesity status
      and insulin sensitivity. Dietary intakes influence metabolic pathways and
      therefore, different dietary patterns may relate to modifications in metabolic
      signatures. The objective was to verify associations between dietary patterns and
      metabolic profiles composed of amino acids (AAs) and acylcarnitines (ACs).
      METHODS: 210 participants were recruited in the greater Quebec City area between
      September 2009 and December 2011. Dietary patterns had been previously derived
      using principal component analysis (PCA). The Prudent dietary pattern was
      characterised by higher intakes of vegetables, fruits, whole grain products, non
      hydrogenated fat and lower intakes of refined grain products, whereas the Western
      dietary pattern was associated with higher intakes of refined grain products,
      desserts, sweets and processed meats. Targeted metabolites were quantified in 37
      participants with the Biocrates Absolute IDQ p150 (Biocrates Life Sciences AG,
      Austria) mass spectrometry method (including 14 amino acids and 41
      acylcarnitines). RESULTS: PCA analysis with metabolites including AAs and ACs
      revealed two main components explaining the most variance in overall data
      (13.8%). PC1 was composed mostly of medium- to long-chain ACs (C16:2, C14:2,
      C14:2-OH, C16, C14:1-OH, C14:1, C10:2, C5-DC/C6-OH, C12, C18:2, C10, C4:1-DC/C6,
      C8:1 and C2) whereas PC2 included certain AAs and short-chain ACs (xLeu, Met,
      Arg, Phe, Pro, Orn, His, C0, C3, C4 and C5). The Western dietary pattern
      correlated negatively with PC1 and positively with PC2 (r = -0.34, p = 0.05 and r
      = 0.38, p = 0.03, respectively), independently of age, sex and BMI. CONCLUSION:
      These findings suggest that the Western dietary pattern is associated with a
      specific metabolite signature characterized by increased levels of AAs including
      branched-chain AAs (BCAAs) and short-chain ACs.

PMID- 24330456
TI  - CPRMethicillin resistant coagulase-negative staphylococci isolated from South
      Korean ducks exhibiting tremor.
AB  - BACKGROUND: We describe coagulase-negative staphylococci (CoNS) isolates
      collected from ducklings exhibiting tremor in South Korea over the period of 2010
      to 2011. Screening of antimicrobial susceptibility and analysis of SCCmec
      elements of CoNS were also investigated. RESULTS: Staphylococcus cohnii was the
      most frequent staphylococcus (9 isolates) and S. sciuri (4 isolates), S. lentus
      (3 isolate), S. simulans (1 isolate) and S. epidermidis (1 isolate) were also
      detected. Among the 15 antimicrobials tested in this study, resistance against
      oxacillin (15 isolates, 83.3%) was most frequently observed, but only one isolate
      (SNUDS-1) possessed mecA. This isolate was shown to possess SCCmec type III; the
      type 3 ccr complex and the class A mec complex. CONCLUSIONS: Based on these
      results, isolate SNUDS-1 was shown to possess SCCmec type III; the type 3 ccr
      complex and the class A mec complex. Although the SCCmec type III is not
      predominant in human, MR-CoNS (Methicillin resistance Coagulase-negative
      staphylococci) in food animals should be monitored to prevent the dissemination
      of antimicrobial resistance genes and resistant pathogens to the community.

PMID- 24330457
TI  - Therapeutic benefit of radiotherapy in huge (>=10 cm) unresectable hepatocellular
      carcinoma.
AB  - BACKGROUND & AIMS: Huge (>=10 cm) hepatocellular carcinomas (HCCs) show dismal
      prognosis and only a limited number of cases are eligible for curative resection.
      We studied the therapeutic benefit of radiotherapy (RT) in patients with huge
      unresectable HCCs. METHODS: Data from 283 patients with huge HCCs and preserved
      liver function who underwent non-surgical treatment from July 2001 to March 2012
      were retrospectively reviewed. Patients were divided into 4 groups according to
      the initial treatment: Group A (N= 49), transarterial chemoembolization (TACE);
      Group B (N = 35), TACE + RT; Group C (N = 50), hepatic arterial infusion
      chemotherapy; and Group D (n = 149), concurrent chemoradiotherapy (CCRT). RESULTS
      AND CONCLUSIONS: The median follow-up period was 27.8 months (range, 12.9-121.9
      months). The median overall survival (OS) was longer in Groups B (15.3 months)
      and D (12.8 months) than in Groups A (7.5 months) and C (8.2 months; Group B vs.
      A, Bonferroni corrected P [P(c)] = 0.04; Group B vs. C, P(c) = 0.02; Group D vs.
      A, P(c) = 0.01; Group D vs. C, Pc = 0.006). Groups B and D also showed superior
      progression-free survival (PFS) and intrahepatic control than Groups A and C. In
      multivariate analysis, tumour multiplicity, serum alpha-foetoprotein level (>=200
      ng/ml) and initial treatment were independent prognostic factors for OS and PFS.
      Patients with huge unresectable HCCs treated with RT, either as CCRT or in
      combination with TACE, showed excellent intrahepatic control and prolonged
      survival. RT could be considered a promising treatment modality in these
      patients.

PMID- 24330458
TI  - Identification of novel genetic markers and evaluation of genetic structure in a
      population of Japanese crested ibis.
AB  - Japanese population of the Japanese crested ibis Nipponia nippon was founded by
      five individuals gifted from the People's Republic of China. In order to exactly
      evaluate genetic structure, we first performed development of novel genetic
      makers using 89 microsatellite primer pairs of related species for cross
      amplification. Of these, only three primer pairs were useful for the genetic
      markers. Additionally, we sequenced allelic PCR products of these three markers
      together with 10 markers previously identified. Most markers showed typical
      microsatellite repeat units, but two markers were not simple microsatellites.
      Moreover, over half of the markers did not have the same repeat units as those of
      the original species. These results suggested that development of novel genetic
      markers in this population by cross-amplification is not efficient, partly
      because of low genetic diversity. Furthermore, the cluster analysis by STRUCTURE
      program using 17 markers showed that the five founders were divided into two
      clusters. However, the genetic relationships among the founders indicated by the
      clustering seemed to be questionable, because the analysis relied largely on a
      small number of triallelic markers, in spite of the addition of the three useful
      markers. Therefore, more efficient methods for identifying large numbers of
      single nucleotide polymorphisms are desirable. 

PMID- 24330459
TI  - School travel and children's physical activity: a cross-sectional study examining
      the influence of distance.
AB  - BACKGROUND: Walking to school is associated with higher levels of physical
      activity. The purpose of this study was to examine the relationship between
      school travel mode and physical activity using a sampling frame that purposefully
      locates schools in varying neighbourhoods. METHODS: Cross-sectional survey of 785
      children (10.57 +/- 0.7 years) in Toronto, Canada. Physical activity was measured
      by accelerometry and travel mode was self-reported by parents. Linear regression
      models accounting for school clustering effects examined the associations between
      mode choice, BMI, and physical activity and were estimated adjusting for age,
      types of neighbourhoods and travel distance to school. RESULTS: Significant
      associations between walking to school and moderate activity during weekdays were
      found. Interactions between walking to school and travel distance to school were
      found only in boys with significant associations between walking to school and
      higher physical activity levels in those living within 1000-1600 meters from
      school. Boys walking to school and living in this range accumulated 7.6 more
      minutes of daily MVPA than boys who were driven. CONCLUSIONS: Walking to school
      can make a modest but significant contribution to overall physical activity. This
      contribution was modified by travel distance and not school neighbourhood
      socioeconomic status or the built environment.

PMID- 24330460
TI  - Chinese Hemophilia Joint Health Score 2.1 reliability study.
AB  - To meet the rapidly expanding need for musculoskeletal (MSK) specialists
      [physiotherapists (PTs), physiatrists] in haemophilia care in China, a 4-day
      Train the Trainer workshop was conducted in July/August 2009 in Beijing. A key
      focus was to train the participants to administer the Hemophilia Joint Health
      Score (HJHS) version 2.1 for effectively evaluating the MSK health of boys <18
      years of age with haemophilia. The aim of this study was to test the HJHS version
      2.1 inter- and intra-rater reliability in a group of Chinese PTs and physiatrists
      with limited experience in haemophilia care. Each of the trained Chinese
      physiatrists and PTs examined eight boys 4-17 years old with moderate and severe
      haemophilia on day 1 and repeated the examination on the same patients the next
      day using the HJHS version 2.1. The boys had a wide range of target joint
      involvement and arthropathy. The HJHS score sheet, work sheets and manual had
      been translated into simple Chinese prior to the study. The interrater (ICC 0.90)
      and intra-rater (ICC 0.91) reliability was excellent. The internal consistency of
      the HJHS items was also excellent with Cronbach's alpha of 0.86. With basic
      training in the administration of the HJHS version 2.1, the tool was reliably
      administered by Chinese PTs and physiatrists with limited haemophilic experience.

PMID- 24330461
TI  - A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders.
AB  - BACKGROUND: The study was designed to evaluate the association of GATA4 gene
      polymorphism with coronary artery disease (CAD) and its metabolic risk factors,
      including dyslipidaemic disorders, obesity, type 2 diabetes and hypertension,
      following a preliminary study linking early onset of CAD in heterozygous familial
      hypercholesterolaemia to chromosome 8, which harbours the GATA4 gene. RESULTS: We
      first sequenced the whole GATA4 gene in 250 individuals to identify variants of
      interest and then investigated the association of 12 single-nucleotide
      polymorphisms (SNPs) with the disease traits using Taqman chemistry in 4,278
      angiographed Saudi individuals. Of the studied SNPs, rs804280 (1.14 (1.03 to
      1.27); p = 0.009) was associated with CAD (2,274 cases vs 2,004 controls),
      hypercholesterolaemia (1,590 vs 2,487) (1.61 (1.03-2.52); p = 0.037) and elevated
      low-density lipoprotein-cholesterol (hLDLC) (575 vs 3,404) (1.87 (1.10-3.15); p =
      0.020). Additionally, rs3729855_T (1.52 (1.09-2.11; p = 0.013)) and rs17153743
      (AG + GG) (2.30 (1.30-4.26); p = 0.005) were implicated in hypertension (3,312 vs
      966), following adjustments for confounders. Furthermore, haplotypes CCCGTGCC
      (chi2 = 4.71; p = 0.041) and GACCCGTG (chi2 = 3.84; p = 0.050) constructed from
      the SNPs were associated with CAD and ACCCACGC (chi2 = 6.58; p = 0.010) with
      myocardial infarction, while hypercholesterolaemia (chi2 = 3.86; p = 0.050) and
      hLDLC (chi2 = 4.94; p = 0.026) shared the AACCCATGT, and AACCCATGTC was
      associated with hLDLC (chi2 = 4.83; p = 0.028). A 10-mer GACCCGCGCC (chi2 = 7.59;
      p = 0.006) was associated with obesity (1,631 vs 2,362), and the GACACACCC (chi2
      = 4.05; p = 0.044) was implicated in type 2 diabetes mellitus 2,378 vs 1,900).
      CONCLUSION: Our study implicates GATA4 in CAD and its metabolic risk traits. The
      finding also points to the possible involvement of yet undefined entities related
      to GATA4 transcription activity or gene regulatory pathways in events leading to
      these cardiovascular disorders.

PMID- 24330463
TI  - Subungual ectopic hair (Onycotrychia).

PMID- 24330462
TI  - A system to simultaneously detect tick-borne pathogens based on the variability
      of the 16S ribosomal genes.
AB  - BACKGROUND: DNA microarrays can be used to quickly and sensitively identify
      several different pathogens in one step. Our previously developed DNA microarray,
      based on the detection of variable regions in the 16S rDNA gene (rrs), which are
      specific for each selected bacterial genus, allowed the concurrent detection of
      Borrelia spp., Anaplasma spp., Francisella spp., Rickettsia spp. and Coxiella
      spp. METHODS: In this study, we developed a comprehensive detection system
      consisting of a second generation DNA microarray and quantitative PCRs. New
      oligonucleotide capture probes specific for Borrelia burgdorferi s.l. genospecies
      and Candidatus Neoehrlichia mikurensis were included. This new DNA microarray
      system required substantial changes in solution composition, hybridization
      conditions and post-hybridization washes. RESULTS: This second generation chip
      displayed high specificity and sensitivity. The specificity of the capture probes
      was tested by hybridizing the DNA microarrays with Cy5-labeled, PCR-generated
      amplicons encoding the rrs genes of both target and non-target bacteria. The
      detection limit was determined to be 10(3) genome copies, which corresponds to 1
      2 pg of DNA. A given sample was evaluated as positive if its mean fluorescence
      was at least 10% of the mean fluorescence of a positive control. Those samples
      with fluorescence close to the threshold were further analyzed using quantitative
      PCRs, developed to identify Francisella spp., Rickettsia spp. and Coxiella spp.
      Like the DNA microarray, the qPCRs were based on the genus specific variable
      regions of the rrs gene. No unspecific cross-reactions were detected. The
      detection limit for Francisella spp. was determined to be only 1 genome copy, for
      Coxiella spp. 10 copies, and for Rickettsia spp., 100 copies. CONCLUSIONS: Our
      detection system offers a rapid method for the comprehensive identification of
      tick-borne bacteria, which is applicable to clinical samples. It can also be used
      to identify both pathogenic and endosymbiontic bacteria in ticks for eco
      epidemiological studies, tick laboratory colony testing, and many other
      applications.

PMID- 24330464
TI  - Dugesia sicula (Platyhelminthes, Tricladida): the colonizing success of an
      asexual Planarian.
AB  - BACKGROUND: Dugesia sicula is the only species of its genus not presenting an
      endemic or restricted distribution within the Mediterranean area. It mostly
      comprises fissiparous populations (asexual reproduction by body division and
      regeneration), most likely sexually sterile, and characterized by an extremely
      low genetic diversity interpreted as the consequence of a recent anthropic
      expansion. However, its fissiparous reproduction can result in an apparent lack
      of diversity within the species, since genetic variation within individuals can
      be as large as between them because most individuals within a population are
      clones. We have estimated haplotype and nucleotide diversity of cytochrome
      oxidase I within and among individuals along the species distribution of a broad
      sample of D. sicula, including asexual and the two only sexual populations known
      today; and predicted its potential distribution based on climatic variables. Our
      aim was to determine the centre of colonisation origin, whether the populations
      are recent, and whether the species is expanding. RESULTS: The species presents 3
      most frequent haplotypes, differing in a maximum of 11 base pairs. As expected
      from their fissiparous mode of reproduction, in half of all the analysed
      localities many individuals have multiple heteroplasmic haplotypes. The
      distribution of haplotypes is not geographically structured; however, the
      distribution of haplotypes and heteroplasmic populations shows higher diversity
      in the central Mediterranean region. The potential distribution predicted by
      climatic variables based modelling shows a preference for coastal areas and fits
      well with the observed data. CONCLUSIONS: The distribution and frequency of the
      most frequent haplotypes and the presence of heteroplasmic individuals allow us
      to gain an understanding of the recent history of the species, together with
      previous knowledge on its phylogenetic relationships and age: The species most
      probably originated in Africa and dispersed through the central Mediterranean.
      After one or multiple populations became triploid and fissiparous, the species
      colonized the Mediterranean basin, likely both by its own means and helped by
      human activities. Its present distribution practically fulfils its potential
      distribution as modelled with climatic variables. Its prevalence in coastal
      regions with higher water temperatures predicts a likely future expansion to
      northern and more interior areas following the increase in temperatures due to
      climate change.

PMID- 24330465
TI  - Total mesorectal excision with water-jet dissection in patients with rectal
      cancer: surgical and morphological aspects.
AB  - AIM: This publication will describe our own experience of using the ERBEJET2((r))
      water-jet dissector during surgical interventions for rectal cancer. METHOD: We
      utilized the water-jet dissection technique to obtain tissue specimens in 10
      patients with rectal cancer. All patients thus underwent nerve-sparing low
      anterior resection of the rectum along with para-aortic lymphadenectomy. No
      intraoperative complications were registered. The postoperative period went
      uncomplicated in all patients. No dysuria was observed. Obtained tissue specimens
      were examined morphologically. Macroscopic examination included assessments of
      the preservation of the rectal fascia propria and the amount of cellular tissue
      along the anterior, posterior, and lateral surfaces of the rectum. We performed
      microscopy of the circumferential resection margin to characterize the surgical
      clearance and the intensity and depth of damage to the mesorectal tissue. On
      morphological examination, the quality of mesorectal excision was found to be
      good (Grade 3) in all 10 patients. RESULTS: As the results of our study
      demonstrate, the depth of lateral tissue damage is minimal with the water-jet
      dissector. CONCLUSION: Water-jet dissectors have their own place in the long list
      of armamentarium used in surgical interventions performed for rectal cancer and
      contribute to improving oncological and functional outcomes of surgical treatment
      in this patient population.

PMID- 24330466
TI  - Does the use of modern family planning promote healthy timing and spacing of
      pregnancy in Dar es Salaam?
AB  - BACKGROUND: Timing, spacing and limiting of pregnancy are key outcomes of family
      planning (FP) whose role in promoting health of mothers and babies is evidence
      based. Despite the evidence, recent studies in Tanzania have reported a trend
      towards child birth in older age, non-adherence to standard inter-pregnancy
      spacing, and preference of large families in the background of a rising national
      contraceptive prevalence rate. We explored if the use of modern FP promotes
      healthy timing and spacing of pregnancy among women seeking antenatal services.
      DESIGN: Analytical Cross-sectional study METHODS: Women seeking antenatal
      services at Muhimbili National Hospital, Tanzania (August-October, 2012) were
      enrolled. We used a semi-structured questionnaire to obtained information from
      the women. Data were analyzed using SPSS version 19. Outcomes of interest were
      adherence to timing of first pregnancy and to inter-pregnancy spacing after
      normal childbirth. Use of modern FP prior to index pregnancy was the independent
      variable of primary interest. Bivariate and multivariate logistic regression
      analyses were conducted to obtain odds ratios (OR) and 95% confidence intervals
      (CI) as estimates risk and clinical importance respectively. Ethical approval was
      obtained from the Research and Publications Committee at Muhimbili University of
      Health and Allied Sciences. RESULTS: In total 427 women were interviewed. Ages
      ranged 15-45 years, mean 29.2 (SD +/- 5.1). Among all, 129 (30.2%) were
      primigravida, 298 (69. 8%) multigravida. Of these 298 women, 51 (17.1%) lost
      pregnancies preceding the index. Overall, 179 (41.9%) had ever used modern FP,
      103 (24.1%) were on modern FP just prior to index pregnancy.Non-adherence to
      timing was increased for primigravida (AOR = 4.5, 95% CI: 2.1-9.6) and for women
      older than 29 years (AOR = 7.6 95% CI: 3.8-15.2). Non-adherence to spacing was
      increased with loss of the immediate past pregnancy (AOR = 2.5; 95% CI: 1.3-4.7).
      Use of modern FP was neither associated with adherence to timing (AOR = 1.0; 95%
      CI: 0.5-1.9) nor spacing (AOR = 1.0; 95% CI: 0.6-1.8). CONCLUSION: Modern FP does
      not promote adherence to timing and spacing of pregnancy among women seeking
      antenatal services at MNH. Past obstetric experience was key to women's decisions
      on spacing. There is need to promote educational messages on timing and spacing
      of pregnancy for healthy outcomes.

PMID- 24330467
TI  - Dose escalation using ultra-high dose IMRT in intermediate risk prostate cancer
      without androgen deprivation therapy: preliminary results of toxicity and
      biochemical control.
AB  - BACKGROUND: To investigate the feasibility of dose escalation (86 Gy at 2
      Gy/fraction) with intensity modulated radiation therapy (IMRT) in intermediate
      risk prostate cancer without androgen deprivation therapy. METHODS: Patients with
      histologically proven adenocarcinoma of the prostate, intermediate prognostic
      category, were enrolled in this study. Early and late toxicity were scored
      according to the Cancer Therapy Evaluation Program, Common Terminology Criteria
      for Adverse Events, Version 3.0. Treatment outcome was stated in terms of
      biochemical failure, biopsy result and clinical failure. RESULTS: 39 patients
      with a median follow-up of 71 months were analyzed. No patient experienced G3 or
      G4 acute gastrointestinal (GI) or genitourinary (GU) toxicity. G2 acute GI and GU
      toxicity were observed in 17 (44%) and 20 (51%) patients, respectively. Fourteen
      patients (36%) did not experience acute GI toxicity and 4 patients (10%) did not
      experience acute GU toxicity. G2 late GI bleeding occurred in 7 of 39 patients
      (18%). Both G3 and G4 late GI toxicity were seen only in one patient (2.5%). Two
      patients (5%) experienced G2 late GU toxicity, while G3 late GU toxicity occurred
      in 3 patients (8%). The 5-year actuarial freedom from biochemical failure (FFBF)
      was 87%. Thirty-four patients (87%) did not show biochemical relapse. Seventeen
      patients (44%) underwent biopsy two year after radiotherapy; of these only two
      were non-negative and both did not show evidence of biochemical disease.
      CONCLUSIONS: IMRT treatment of patients with localized intermediate-risk prostate
      cancer at high dose levels without using androgen deprivation therapy (ADT) seems
      to give good disease control. Nevertheless, future trials should aim at further
      decreasing toxicity by exploiting image guidance techniques and by reducing the
      dose delivered at the interface between organs at risk and prostate.

PMID- 24330468
TI  - Visual performance and ocular abnormalities in deaf children and young adults: a
      literature review.
AB  - Visual defects are common in deaf individuals. Refractive error and ocular motor
      abnormalities are frequently reported, with hyperopia, myopia, astigmatism and
      anomalies of binocular vision, all showing a greater prevalence in deaf
      individuals compared with the general population. Near visual function in deaf
      individuals has been relatively neglected in the literature to date. Comparisons
      between studies are problematic due to differences in methodology and population
      characteristics. Any untreated visual defect has the potential to impair the
      development of language, with consequences for education more generally, and
      there is a need to improve screening and treatments of deaf children. 

PMID- 24330469
TI  - The Visual Spatial Learning Test: differential impairment during the premanifest
      and manifest stages of Huntington's disease.
AB  - Visual spatial memory was assessed using the Visual Spatial Learning Test (VSLT)
      in individuals with mild to moderate Huntington's disease (HD), pre-manifest gene
      carriers for HD, and demographically similar controls. The VSLT has been
      demonstrated to be a valid, normed measure of non-verbal memory involving minimal
      motoric responses. The VSLT assesses immediate and delayed memory for designs,
      positions of the designs, and design/position associations. The HD group was
      significantly impaired (p < .05) relative to both the control and Pre-HD groups
      on immediate and delayed memory for the designs, positions, and design/position
      associations. Although there were no differences between the Pre-HD and control
      groups on immediate or delayed memory for designs or positions, the Pre-HD group
      was significantly impaired (p < .05) relative to the control group on immediate
      and delayed memory for design/position associations. The results offer novel
      insight into a relatively unexamined memory deficit that may occur in gene
      carriers for HD prior to phenoconversion. The data indicate that the VSLT may be
      a useful measure of visuospatial memory during the premanifest and manifest
      stages of HD.

PMID- 24330470
TI  - Evaluation of patient-centered rehabilitation model targeting older persons with
      a hip fracture, including those with cognitive impairment.
AB  - BACKGROUND: The purpose of this study was to evaluate outcomes for older persons
      post-hip fracture repair, including those with cognitive impairment (CI),
      following implementation of a novel model of care - the Patient-Centered
      Rehabilitation Model including persons with CI (PCRM-CI). The PCRM-CI is an
      interdisciplinary rehabilitation program that incorporates education for
      healthcare professionals (HCPs), including nurses, which is focused on geriatric
      care including management of dementia and delirium, support for HCPs from an
      Advanced Practice Nurse, and family support and education. Primary outcome
      measures were mobility gain from admission to discharge and whether or not
      patients returned home post-discharge. METHODS: The PCRM-CI intervention was
      evaluated using a quasi-experimental design, following implementation in two
      community hospital inpatient rehabilitation units. One hundred forty-nine
      patients aged 65 and older participated as patients in the usual care (76) or
      PCRM-CI intervention (73) groups. Patient mobility was assessed at admission and
      discharge by the Functional Independence Measure Motor Subscale (FIMM); the
      difference in mobility scores was defined as mobility gain. Patient discharge
      location was also captured to determine whether or not patients returned home
      from inpatient rehabilitation. RESULTS: No difference in mobility gain was found
      between the usual care and PCRM-CI groups as measured by the FIMM. Patients in
      the intervention group were more likely to return home post-discharge than those
      in the usual care group (p = 0.02). CONCLUSIONS: Results of the PCRM-CI
      evaluation suggest that older adults with CI can successfully be rehabilitated
      post-hip fracture repair using this novel, interdisciplinary rehabilitation
      program.

PMID- 24330471
TI  - Functional characterization of two members of histidine phosphatase superfamily
      in Mycobacterium tuberculosis.
AB  - BACKGROUND: Functional characterization of genes in important pathogenic bacteria
      such as Mycobacterium tuberculosis is imperative. Rv2135c, which was originally
      annotated as conserved hypothetical, has been found to be associated with
      membrane protein fractions of H37Rv strain. The gene appears to contain histidine
      phosphatase motif common to both cofactor-dependent phosphoglycerate mutases and
      acid phosphatases in the histidine phosphatase superfamily. The functions of many
      of the members of this superfamily are annotated based only on similarity to
      known proteins using automatic annotation systems, which can be erroneous. In
      addition, the motif at the N-terminal of Rv2135c is 'RHA' unlike 'RHG' found in
      most members of histidine phosphatase superfamily. These necessitate the need for
      its experimental characterization. The crystal structure of Rv0489, another
      member of the histidine phosphatase superfamily in M. tuberculosis, has been
      previously reported. However, its biochemical characteristics remain unknown. In
      this study, Rv2135c and Rv0489 from M. tuberculosis were cloned and expressed in
      Escherichia coli with 6 histidine residues tagged at the C terminal. RESULTS:
      Characterization of the purified recombinant proteins revealed that Rv0489
      possesses phosphoglycerate mutase activity while Rv2135c does not. However
      Rv2135c has an acid phosphatase activity with optimal pH of 5.8. Kinetic
      parameters of Rv2135c and Rv0489 are studied, confirming that Rv0489 is a
      cofactor dependent phosphoglycerate mutase of M. tuberculosis. Additional
      characterization showed that Rv2135c exists as a tetramer while Rv0489 as a dimer
      in solution. CONCLUSION: Most of the proteins orthologous to Rv2135c in other
      bacteria are annotated as phosphoglycerate mutases or hypothetical proteins. It
      is possible that they are actually phosphatases. Experimental characterization of
      a sufficiently large number of bacterial histidine phosphatases will increase the
      accuracy of the automatic annotation systems towards a better understanding of
      this important group of enzymes.

PMID- 24330472
TI  - Lessons learned from stakeholders in a facilitation intervention targeting
      neonatal health in Quang Ninh province, Vietnam.
AB  - BACKGROUND: In northern Vietnam the Neonatal health - Knowledge Into Practice
      (NeoKIP, Current Controlled Trials ISRCTN44599712) trial has evaluated
      facilitation as a knowledge translation intervention to improve neonatal
      survival. The results demonstrated that intervention sites, each having an
      assigned group including local stakeholders supported by a facilitator, lowered
      the neonatal mortality rate by 50% during the last intervention year compared
      with control sites. This process evaluation was conducted to identify and
      describe mechanisms of the NeoKIP intervention based on experiences of
      facilitators and intervention group members. METHODS: Four focus group
      discussions (FGDs) were conducted with all facilitators at different occasions
      and 12 FGDs with 6 intervention groups at 2 occasions. Fifteen FGDs were audio
      recorded, transcribed verbatim, translated into English, and analysed using
      thematic analysis. RESULTS: Four themes and 17 sub-themes emerged from the 3 FGDs
      with facilitators, and 5 themes and 18 sub-themes were identified from the 12
      FGDs with the intervention groups mirroring the process of, and the barriers to,
      the intervention. Facilitators and intervention group members concurred that
      having groups representing various organisations was beneficial. Facilitators
      were considered important in assembling the groups. The facilitators functioned
      best if coming from the same geographical area as the groups and if they were
      able to come to terms with the chair of the groups. However, the facilitators'
      lack of health knowledge was regarded as a deficit for assisting the groups'
      assignments. FGD participants experienced the NeoKIP intervention to have impact
      on the knowledge and behaviour of both intervention group members and the general
      public, however, they found that the intervention was a slow and time-consuming
      process. Perceived facilitation barriers were lack of money, inadequate support,
      and the function of the intervention groups. CONCLUSIONS: This qualitative
      process evaluation contributes to explain the improved neonatal survival and why
      this occurred after a latent period in the NeoKIP project. The used knowledge
      translation intervention, where facilitators supported multi-stakeholder
      coalitions with the mandate to impact upon attitudes and behaviour in the
      communes, has low costs and potential for being scaled-up within existing
      healthcare systems.

PMID- 24330473
TI  - Short- and long-term effects of tactile massage on salivary cortisol
      concentrations in Parkinson's disease: a randomised controlled pilot study.
AB  - BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder with
      limited knowledge about the normal function and effects of non-pharmacological
      therapies on the hypothalamic-pituitary-adrenal (HPA) axis. The aim of the study
      was to analyse the basal diurnal and total secretion of salivary cortisol in
      short- and long-term aspects of tactile massage (TM). METHODS:  DESIGN:
      Prospective, Controlled and Randomised Multicentre Trial. SETTING AND
      INTERVENTIONS: Forty-five women and men, aged 50-79 years, were recruited. Twenty
      nine of them were blindly randomised to tactile massage (TM) and 16 of them to
      the control group, rest to music (RTM). Ten interventions were given during 8
      weeks followed by a 26 weeks of follow up. Salivary cortisol was collected at 8
      am, 1 pm, 8 pm, and 8 am the next day, on five occasions. With the first and
      eighth interventions, it was collected immediately before and after intervention.
      MAIN OUTCOME MEASURES: The primary aim was to assess and compare cortisol
      concentrations before and immediately after intervention and also during the
      follow-up period. The secondary aim was to assess the impact of age, gender, body
      mass index (BMI), duration and severity of PD, effects of interventional time
      point of the day, and levodopa doses on cortisol concentration. RESULTS: The
      median cortisol concentrations for all participants were 16.0, 5.8, 2.8, and 14.0
      nmol/L at baseline, later reproduced four times without significant differences.
      Cortisol concentrations decreased significantly after TM intervention but no
      change in diurnal salivary cortisol pattern was found. The findings of reduced
      salivary cortisol concentrations immediately after the interventions are in
      agreement with previous studies. However, there was no significant difference
      between the TM and control groups. There were no significant correlations between
      cortisol concentrations and age, gender, BMI, time-point for intervention, time
      interval between anti-parkinson pharmacy intake and sampling, levodopa doses,
      duration, or severity of PD. CONCLUSIONS: Diurnal salivary cortisol rhythm was
      normal. Salivary cortisol concentrations were significantly reduced after the TM
      intervention and after RTM, but there were no significant differences between the
      groups and no sustained long-term effect. No associations were seen between
      salivary cortisol concentration and clinical and/or pharmacological
      characteristics. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01734876 and FoU
      Sweden 108881.

PMID- 24330474
TI  - Analysis of mass spectrometry data from the secretome of an explant model of
      articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli
      using machine learning.
AB  - BACKGROUND: Osteoarthritis (OA) is an inflammatory disease of synovial joints
      involving the loss and degeneration of articular cartilage. The gold standard for
      evaluating cartilage loss in OA is the measurement of joint space width on
      standard radiographs. However, in most cases the diagnosis is made well after the
      onset of the disease, when the symptoms are well established. Identification of
      early biomarkers of OA can facilitate earlier diagnosis, improve disease
      monitoring and predict responses to therapeutic interventions. METHODS: This
      study describes the bioinformatic analysis of data generated from high throughput
      proteomics for identification of potential biomarkers of OA. The mass
      spectrometry data was generated using a canine explant model of articular
      cartilage treated with the pro-inflammatory cytokine interleukin 1 beta (IL
      1beta). The bioinformatics analysis involved the application of machine learning
      and network analysis to the proteomic mass spectrometry data. A rule based
      machine learning technique, BioHEL, was used to create a model that classified
      the samples into their relevant treatment groups by identifying those proteins
      that separated samples into their respective groups. The proteins identified were
      considered to be potential biomarkers. Protein networks were also generated; from
      these networks, proteins pivotal to the classification were identified. RESULTS:
      BioHEL correctly classified eighteen out of twenty-three samples, giving a
      classification accuracy of 78.3% for the dataset. The dataset included the four
      classes of control, IL-1beta, carprofen, and IL-1beta and carprofen together.
      This exceeded the other machine learners that were used for a comparison, on the
      same dataset, with the exception of another rule-based method, JRip, which
      performed equally well. The proteins that were most frequently used in rules
      generated by BioHEL were found to include a number of relevant proteins including
      matrix metalloproteinase 3, interleukin 8 and matrix gla protein. CONCLUSIONS:
      Using this protocol, combining an in vitro model of OA with bioinformatics
      analysis, a number of relevant extracellular matrix proteins were identified,
      thereby supporting the application of these bioinformatics tools for analysis of
      proteomic data from in vitro models of cartilage degradation.

PMID- 24330475
TI  - Maintaining remission in lamivudine-resistant patients with a virological
      response to adefovir add-on lamivudine after stopping lamivudine therapy.
AB  - BACKGROUND & AIMS: We examined the durability of the virological response after
      discontinuing lamivudine (LVD) in chronic hepatitis B (CHB) patients with LVD
      resistant hepatitis B virus (HBV), who responded to LVD plus adefovir (ADV)
      combination therapy, and the outcome of switching to ADV monotherapy compared to
      maintaining combination therapy. METHODS: This study enrolled 72 patients with
      undetectable viral loads (<=12 IU/ml) and normal alanine aminotransferase levels
      after ADV add-on therapy for at least 6 months in LVD-resistant CHB patients. The
      enrolled patients were randomly assigned to continue with LVD-ADV combination
      therapy or switch to ADV monotherapy (n = 36 per group). Virological rebound was
      defined as HBV DNA detection at more than 12 IU/ml by quantitative polymerase
      chain reaction determined on two consecutive measurements. RESULTS: During 96
      weeks of follow-up, 100% (36/36) of the patients in the LVD-ADV combination
      maintained group had persistently undetectable HBV DNA, compared with 94.4%
      (34/36) patients in the ADV monotherapy switched group. These two patients had
      undetectable HBV DNA after switching back to LVD-ADV combination therapy. There
      were no significant differences in the HBsAg levels between the two treatment
      groups during the 96-week follow-up period. CONCLUSIONS: In our study, switching
      to ADV monotherapy resulted in sustained HBV DNA suppression in 94.4% of the
      patients for 96 weeks. Prior complete viral suppression with LVD-ADV combination
      therapy conferred a significant advantage in patients who switched to ADV
      monotherapy. LVD may be discontinued in patients who show a complete virological
      response to LVD-ADV combination therapy for at least 6 months.

PMID- 24330476
TI  - Bovine Tuberculosis Risk Factors for British Herds Before and After the 2001 Foot
      and-Mouth Epidemic: What have we Learned from the TB99 and CCS2005 Studies?
AB  - Over the last couple of decades, the UK experienced a substantial increase in the
      incidence and geographical spread of bovine tuberculosis (TB), in particular
      since the epidemic of foot-and-mouth disease (FMD) in 2001. The initiation of the
      Randomized Badger Culling Trial (RBCT) in 1998 in south-west England provided an
      opportunity for an in-depth collection of questionnaire data (covering farming
      practices, herd management and husbandry, trading and wildlife activity) from
      herds having experienced a TB breakdown between 1998 and early 2006 and randomly
      selected control herds, both within and outside the RBCT (the so-called TB99 and
      CCS2005 case-control studies). The data collated were split into four separate
      and comparable substudies related to either the pre-FMD or post-FMD period, which
      are brought together and discussed here for the first time. The findings suggest
      that the risk factors associated with TB breakdowns may have changed. Higher
      Mycobacterium bovis prevalence in badgers following the FMD epidemic may have
      contributed to the identification of the presence of badgers on a farm as a
      prominent TB risk factor only post-FMD. The strong emergence of contact/trading
      TB risk factors post-FMD suggests that the purchasing and movement of cattle,
      which took place to restock FMD-affected areas after 2001, may have exacerbated
      the TB problem. Post-FMD analyses also highlighted the potential impact of
      environmental factors on TB risk. Although no unique and universal solution
      exists to reduce the transmission of TB to and among British cattle, there is an
      evidence to suggest that applying the broad principles of biosecurity on farms
      reduces the risk of infection. However, with trading remaining as an important
      route of local and long-distance TB transmission, improvements in the detection
      of infected animals during pre- and post-movement testing should further reduce
      the geographical spread of the disease.

PMID- 24330477
TI  - Honey bee hygienic behaviour does not incur a cost via removal of healthy brood.
AB  - In the honey bee, hygienic behaviour, the removal of dead or diseased brood from
      capped cells by workers, is a heritable trait that confers colony-level
      resistance against brood diseases. This behaviour is quite rare. Only c. 10% of
      unselected colonies show high levels of hygiene. Previous studies suggested that
      hygiene might be rare because it also results in the removal of healthy brood,
      thereby imposing an ongoing cost even when brood diseases are absent. We tested
      this hypothesis by quantifying hygienic behaviour in 10 colonies using a standard
      technique, the freeze-killed brood (FKB) bioassay. At the same time, we also
      quantified the removal of untreated brood. The study colonies showed a wide range
      in hygienic behaviour, removing 19.7-100% of the FKB. The removal of untreated
      brood ranged from 2% to 44.4%. However, there was no correlation between the two
      removal rates for any of the four age groups of untreated brood studied (eggs,
      young larvae, older larvae from uncapped cells and larvae/pupae from capped
      cells). These results do not support the cost-to-healthy-brood hypothesis for the
      rarity of hygienic behaviour. 

PMID- 24330478
TI  - Analyses of amplified fragment length polymorphisms (AFLP) indicate rapid
      radiation of Diospyros species (Ebenaceae) endemic to New Caledonia.
AB  - BACKGROUND: Radiation in some plant groups has occurred on islands and due to the
      characteristic rapid pace of phenotypic evolution, standard molecular markers
      often provide insufficient variation for phylogenetic reconstruction. To resolve
      relationships within a clade of 21 closely related New Caledonian Diospyros
      species and evaluate species boundaries we analysed genome-wide DNA variation via
      amplified fragment length polymorphisms (AFLP). RESULTS: A neighbour-joining (NJ)
      dendrogram based on Dice distances shows all species except D. minimifolia, D.
      parviflora and D. vieillardii to form unique clusters of genetically similar
      accessions. However, there was little variation between these species clusters,
      resulting in unresolved species relationships and a star-like general NJ
      topology. Correspondingly, analyses of molecular variance showed more variation
      within species than between them. A Bayesian analysis with BEAST produced a
      similar result. Another Bayesian method, this time a clustering method,
      Structure, demonstrated the presence of two groups, highly congruent with those
      observed in a principal coordinate analysis (PCO). Molecular divergence between
      the two groups is low and does not correspond to any hypothesised taxonomic,
      ecological or geographical patterns. CONCLUSIONS: We hypothesise that such a
      pattern could have been produced by rapid and complex evolution involving a
      widespread progenitor for which an initial split into two groups was followed by
      subsequent fragmentation into many diverging populations, which was followed by
      range expansion of then divergent entities. Overall, this process resulted in an
      opportunistic pattern of phenotypic diversification. The time since divergence
      was probably insufficient for some species to become genetically well
      differentiated, resulting in progenitor/derivative relationships being exhibited
      in a few cases. In other cases, our analyses may have revealed evidence for the
      existence of cryptic species, for which more study of morphology and ecology are
      now required.

PMID- 24330479
TI  - Multiple types of data are required to identify the mechanisms influencing the
      spatial expansion of melanoma cell colonies.
AB  - BACKGROUND: The expansion of cell colonies is driven by a delicate balance of
      several mechanisms including cell motility, cell-to-cell adhesion and cell
      proliferation. New approaches that can be used to independently identify and
      quantify the role of each mechanism will help us understand how each mechanism
      contributes to the expansion process. Standard mathematical modelling approaches
      to describe such cell colony expansion typically neglect cell-to-cell adhesion,
      despite the fact that cell-to-cell adhesion is thought to play an important role.
      RESULTS: We use a combined experimental and mathematical modelling approach to
      determine the cell diffusivity, D, cell-to-cell adhesion strength, q, and cell
      proliferation rate, lambda, in an expanding colony of MM127 melanoma cells. Using
      a circular barrier assay, we extract several types of experimental data and use a
      mathematical model to independently estimate D, q and lambda. In our first set of
      experiments, we suppress cell proliferation and analyse three different types of
      data to estimate D and q. We find that standard types of data, such as the area
      enclosed by the leading edge of the expanding colony and more detailed cell
      density profiles throughout the expanding colony, does not provide sufficient
      information to uniquely identify D and q. We find that additional data relating
      to the degree of cell-to-cell clustering is required to provide independent
      estimates of q, and in turn D. In our second set of experiments, where
      proliferation is not suppressed, we use data describing temporal changes in cell
      density to determine the cell proliferation rate. In summary, we find that our
      experiments are best described using the range D=161-243MUm2 hour-1, q=0.3-0.5
      (low to moderate strength) and lambda=0.0305-0.0398 hour-1, and with these
      parameters we can accurately predict the temporal variations in the spatial
      extent and cell density profile throughout the expanding melanoma cell colony.
      CONCLUSIONS: Our systematic approach to identify the cell diffusivity, cell-to
      cell adhesion strength and cell proliferation rate highlights the importance of
      integrating multiple types of data to accurately quantify the factors influencing
      the spatial expansion of melanoma cell colonies.

PMID- 24330481
TI  - Burden of micronutrient deficiencies by socio-economic strata in children aged 6
      months to 5 years in the Philippines.
AB  - BACKGROUND: Micronutrient deficiencies (MNDs) are a chronic lack of vitamins and
      minerals and constitute a huge public health problem. MNDs have severe health
      consequences and are particularly harmful during early childhood due to their
      impact on the physical and cognitive development. We estimate the costs of
      illness due to iron deficiency (IDA), vitamin A deficiency (VAD) and zinc
      deficiency (ZnD) in 2 age groups (6-23 and 24-59 months) of Filipino children by
      socio-economic strata in 2008. METHODS: We build a health economic model
      simulating the consequences of MNDs in childhood over the entire lifetime. The
      model is based on a health survey and a nutrition survey carried out in 2008. The
      sample populations are first structured into 10 socio-economic strata (SES) and 2
      age groups. Health consequences of MNDs are modelled based on information
      extracted from literature. Direct medical costs, production losses and intangible
      costs are computed and long term costs are discounted to present value. RESULTS:
      Total lifetime costs of IDA, VAD and ZnD amounted to direct medical costs of 30
      million dollars, production losses of 618 million dollars and intangible costs of
      122,138 disability adjusted life years (DALYs). These costs can be interpreted as
      the lifetime costs of a 1-year cohort affected by MNDs between the age of 6-59
      months. Direct medical costs are dominated by costs due to ZnD (89% of total),
      production losses by losses in future lifetime (90% of total) and intangible
      costs by premature death (47% of total DALY losses) and losses in future lifetime
      (43%). Costs of MNDs differ considerably between SES as costs in the poorest
      third of the households are 5 times higher than in the wealthiest third.
      CONCLUSIONS: MNDs lead to substantial costs in 6-59-month-old children in the
      Philippines. Costs are highly concentrated in the lower SES and in children 6-23
      months old. These results may have important implications for the design,
      evaluation and choice of the most effective and cost-effective policies aimed at
      the reduction of MNDs.

PMID- 24330482
TI  - Children's cognitive recovery after day-case general anesthesia: a randomized
      trial of propofol or isoflurane for dental procedures.
AB  - BACKGROUND: Postoperative cognitive dysfunction (POCD) is well established in
      adults but has been underinvestigated in children. As day-case procedures are
      increasingly common, it is important to establish whether children suffer
      significant POCD. Pediatric POCD has been associated with several intravenous and
      inhalation anesthetics, but isoflurane has not been studied. As evidence
      indicates superior recovery after propofol, the study compared POCD after
      propofol or isoflurane anesthesia. OBJECTIVES: To compare the effects of propofol
      versus isoflurane upon children's POCD. METHODS: Fifty-eight children aged 5-14
      years were randomized to propofol (total intravenous anesthesia) or isoflurane
      for day-case dental procedures. Reaction time (RT), verbal and visual memory,
      psychomotor coordination, and attention were assessed preoperatively, prior to
      discharge and at 24 h. RESULTS: Reaction time and psychomotor control were
      impaired postoperatively in both groups but recovered at 24 h. Delayed verbal
      recall was significantly impaired only after propofol. Both groups had
      significant impairment of visual memory postoperatively and at 24 h, and of
      recognition memory postoperatively only. CONCLUSIONS: Propofol and isoflurane
      exert similar adverse effects on RT, psychomotor coordination, and visual memory.
      Selective impairment of verbal recall by propofol is consistent with adult
      evidence of the drug's effect on retrieval. The enduring postoperative impairment
      of memory has implications for instructions to parents and caregivers for the
      safety and well-being of children in the 24 h after day-case anesthesia with
      propofol and isoflurane.

PMID- 24330483
TI  - Multiplication of the waterborne pathogen Cryptosporidium parvum in an aquatic
      biofilm system.
AB  - BACKGROUND: In natural aquatic environments biofilms are known to act as
      environmental reservoirs for Cryptosporidium parvum oocysts. However, the fate of
      these oocysts within biofilms has yet to be determined. METHODS: This study aimed
      to identify if biofilms have the ability to support the multiplication of
      Cryptosporidium by measuring the change in parasite number over time using
      quantitative polymerase chain reaction (qPCR) and detecting the possible
      extracellular developmental stages using a combination of confocal microscopy and
      immunolabelling techniques. Pseudomonas aeruginosa biofilm flow cell systems were
      established and C. parvum oocysts were constantly supplied over a six day period.
      RESULTS: A significant (P<0.001) increase in Cryptosporidium was detected as the
      biofilm matured, with the total number of C. parvum multiplying 2-3 fold during
      this period. With this, various Cryptosporidium developmental stages
      (sporozoites, trophozoites, type I and II meronts) were identified from the
      biofilm. CONCLUSION: This is the first study demonstrating that biofilms not only
      serve as an environmental reservoir for oocysts, but are also capable of
      supporting the multiplication of Cryptosporidium over time in an aquatic
      environment.

PMID- 24330485
TI  - Heavy metals in locus ceruleus and motor neurons in motor neuron disease.
AB  - BACKGROUND: The causes of sporadic amyotrophic lateral sclerosis (SALS) and other
      types of motor neuron disease (MND) remain largely unknown. Heavy metals have
      long been implicated in MND, and it has recently been shown that inorganic
      mercury selectively enters human locus ceruleus (LC) and motor neurons. We
      therefore used silver nitrate autometallography (AMG) to look for AMG-stainable
      heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24
      patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24
      controls. RESULTS: Heavy metals in neurons were found in significantly more MND
      patients than in controls when comparing: (1) the presence of any versus no heavy
      metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of
      heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of
      individuals with heavy metal-containing LC neurons in the upper half of the
      percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining
      spinal motor neurons contained heavy metals; smaller percentages were found in
      hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor
      neurons. The majority of MND patients had heavy metals in both LC and spinal
      motor neurons. No glia or other neurons, including neuromelanin-containing
      neurons of the substantia nigra, contained stainable heavy metals. CONCLUSIONS:
      Uptake of heavy metals by LC and lower motor neurons appears to be fairly common
      in humans, though heavy metal staining in the LC, most likely due to inorganic
      mercury, was seen significantly more often in MND patients than in controls. The
      LC innervates many cell types that are affected in MND, and it is possible that
      MND is triggered by toxicant-induced interactions between LC and motor neurons.

PMID- 24330484
TI  - Hyponatremia and anti-diuretic hormone in Legionnaires' disease.
AB  - BACKGROUND: Medical textbooks often list Legionnaires' disease as a differential
      diagnosis of the syndrome of inappropriate secretion of anti-diuretic hormone
      (ADH) (SIADH), but evidence supporting this association is largely lacking. We
      tested the hypothesis whether hyponatremia in patients with Legionnaires' disease
      would be caused by increased CT-ProVasopressin. METHODS: We measured CT
      ProVasopressin and sodium levels in a prospective cohort of 873 pneumonia
      patients from a previous multicentre study with 27 patients having positive
      antigen tests for Legionella pneumophila. RESULTS: Patients with Legionnaires'
      disease more frequently had low sodium levels (Na < 130 mmol/L) (44.4% vs 8.2%, p
      < 0.01), but similar mean CT-ProVasopressin levels (pmol/l) (39.4 [+/-7] vs 51.2
      [+/-2.7], p = 0.43) as compared to patients with pneumonia of other etiologies.
      In patients with Legionnaires' disease, CT-ProVasopressin levels showed a
      positive correlation with sodium (r = 0.42, p < 0.05). Independent of pneumonia
      etiology, CT-ProVasopressin correlated significantly with the pneumonia severity
      index (r = 0.56, p < 0.05), ICU admission (adjusted odds ratio per decile, 95%
      CI) (1.6, 1.2 - 2.0), and 30-day-mortality (1.8, 1.3 - 2.4). CONCLUSION: While
      Legionnaires' disease was associated with hyponatremia, no concurrent increase in
      CT-ProVasopressin levels was found, which argues against elevated ADH levels as
      the causal pathway to hyponatremia. Rather, Vasopressin precursors were
      upregulated as response to stress in severe disease, which seems to overrule the
      osmoregulatory regulation of ADH.

PMID- 24330486
TI  - Genetic profile and cancer-related pain: a tale from two outlier cases with bone
      metastatic disease.

PMID- 24330487
TI  - Awareness and knowledge on timing of mother-to-child transmission of HIV among
      antenatal care attending women in Southern Ethiopia: a cross sectional study.
AB  - BACKGROUND: Mother-to-child transmission (MTCT) of HIV infection remains a major
      public health problem and constitutes the most important cause of HIV infection
      in children under the age of 15 years old. Awareness on MTCT of HIV and knowledge
      of its timing usually pose a direct effect on utilization of PMTCT services
      (mainly HIV testing, infant feeding options and antiretroviral use). The
      objective of this study is to assess pregnant women's knowledge on timing of MTCT
      of HIV in Southern Ethiopia. METHODS: A cross sectional study was conducted in 62
      health centers in Southern Ethiopia from February 25 to March 24, 2012. A total
      of 1325 antenatal care attending women were included in the survey by using a
      multistage sampling technique. Data were collected using a structured and pre
      tested questionnaire. Multiple logistic regression analysis was employed to
      identify variables associated with women's knowledge on timing of MTCT of HIV.
      RESULTS: All interviewed pregnant women were aware of HIV/AIDS transmission, but
      only 60.7% were aware of the risk of MTCT. The possibility of MTCT during
      pregnancy, delivery and breastfeeding was known by 48.4%, 58.6% and 40.7% of the
      respondents, respectively. The proportion of women who were fully knowledgeable
      on timing of MTCT was 11.5%. Women's full knowledge on timing of MTCT was
      associated with maternal education [AOR = 3.68, 95% CI: 1.49-9.08], and being
      government employee [AOR = 2.50, 95% CI: 1.23- 5.07]. Whereas, there was a
      negative association between full knowledge of women on timing of MTCT and no
      offer of information on MTCT/PMTCT by antenatal care (ANC) service provider [AOR
      = 0.44, 95% CI: 0.30-0.64], lack of discussion on ANC with male partner [AOR =
      0.30, 95% CI: 0.12-0.72], and lack of discussion on HIV/AIDS with male partner
      [AOR = 0.17, 95% CI: 0.07-0.43]. CONCLUSION: There was low awareness and
      knowledge on timing of MTCT of HIV in this study. Hence, strengthening the level
      of PMTCT services in ANC settings and devising mechanisms to promote involvement
      of men in PMTCT services is needed.

PMID- 24330488
TI  - Changes induced by diet and nutritional intake in the lipid profile of female
      professional volleyball players after 11 weeks of training.
AB  - BACKGROUND: The relationship between cardiovascular disease and lipid profile is
      well known. Apart from a heart-healthy diet, exercise is the primary factor that
      can modify this lipid-associated cardiovascular risk. The aim of the study was to
      evaluate potential changes in the levels of triglycerides, total cholesterol
      (TC), low-density lipoprotein-cholesterol (LDLc), and high-density lipoprotein
      cholesterol (HDLc), as well as atherogenic indices (TC/HDLc and LDLc/HDLc), and
      also to analyse the diet over 11 weeks of training in female professional
      volleyball players. METHODS: The lipid profile of 22 female professional
      volleyball players was analysed on Day T0 (pre-preseason) and Day T11 (after 11
      weeks of training). The consumption of fats by the players was estimated using a
      food frequency questionnaire, confirmed by seven days of full dietary records.
      RESULTS: By the end of the study, the LDLc levels and both atherogenic indices of
      the players had decreased (p < 0.05) compared to the values obtained at baseline.
      In addition, the diet of the players contained 35.5 +/- 3.2% of fats (saturated
      fatty acid: 11.1 +/- 1.2%, monounsaturated fatty acid: 14.3 +/- 1.9%, and
      polyunsaturated fatty acid: 7.0 +/- 1.1%) and 465 +/- 57 mg of dietary
      cholesterol. Their score for the (monounsaturated + polyunsaturated fatty
      acid)/saturated fatty acid ratio was 1.9 +/- 0.4, less than the recommended >= 2.
      CONCLUSION: These data indicate that the activity of the female professional
      volleyball players during the first 11 weeks of training in the season was heart
      healthy, because their lipid profile improved, despite an inadequate intake of
      fats.

PMID- 24330489
TI  - Treating to the target of remission in early rheumatoid arthritis is cost
      effective: results of the DREAM registry.
AB  - BACKGROUND: Where health economic studies are frequently performed using
      modelling, with input from randomized controlled trials and best guesses, we used
      real-life data to analyse the cost-effectiveness and cost-utility of a treatment
      strategy aiming to the target of remission compared to usual care in early
      rheumatoid arthritis (RA). METHODS: We used real-life data from comparable
      cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM
      remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA
      inception cohort (usual care, UC). Both cohorts were followed prospectively using
      the DREAM registry methodology. All patients fulfilled the American College of
      Rheumatology criteria for RA and were included in the cohort at the time of
      diagnosis. The T2T cohort was treated according to a protocolised strategy aiming
      at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort
      was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores
      were estimated from the Health Assessment Questionnaire. A health care
      perspective was adopted and direct medical costs were collected. The incremental
      cost effectiveness ratio (ICER) per patient in remission and incremental cost
      utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated
      over two and three years of follow-up. RESULTS: Two year data were available for
      261 T2T patients and 213 UC patients; an extended follow-up of three years was
      available for 127 and 180 patients, respectively. T2T produced higher remission
      percentages and a larger gain in QALYs than UC. The ICER was ? 3,591 per patient
      in remission after two years and T2T was dominant after three years. The ICUR was
      ? 19,410 per QALY after two years and T2T was dominant after three years.
      CONCLUSIONS: We can conclude that treating to the target of remission in early RA
      is cost-effective compared with UC. The data suggest that in the third year, T2T
      becomes cost-saving.

PMID- 24330490
TI  - Comparison of pulp response to mineral trioxide aggregate and a bioceramic paste
      in partial pulpotomy of sound human premolars: a randomized controlled trial.
AB  - AIM: This randomized clinical trial evaluated clinical sign/symptoms as well as
      histological pulp reactions in terms of inflammation and mineralized bridge
      formation after partial pulpotomy of sound human premolars and placement of a
      bioceramic paste (iRoot BP) or tooth-colored ProRoot MTA as pulp-covering
      biomaterials. METHODOLOGY: Twenty-four human sound premolars were randomly
      allocated into two experimental groups (n = 12) treated either with iRoot BP or
      MTA subsequent to partial pulpotomy. Six weeks after treatment, clinical
      sign/symptoms and radiographic changes were evaluated. The teeth were then
      extracted and examined histologically for inflammatory status of the pulp,
      formation of hard tissue bridge and appearance of the bridge. In terms of pulp
      inflammation and dentinal bridge formation, the Mann-Whitney U, and for clinical
      signs, the chi-square test was used (alpha = 0.05). RESULTS: In terms of pulp
      inflammation, formation of hard tissue bridge and its appearance, the differences
      between the two experimental groups were not significant. However, clinical
      sensitivity to cold was significantly less for teeth treated with MTA (P < 0.05).
      All cases had formed a hard tissue bridge, and none of the specimens in either
      group had pulpal necrosis. CONCLUSION: When treating teeth with healthy pulps,
      the response to partial pulpotomy treatment with both MTA and iRoot BP was
      favourable. However, pulps covered with iRoot BP were more sensitive to cold
      stimuli.

PMID- 24330492
TI  - Ophthalmologists play a key role in the management of syphilis presenting with
      ocular involvement.

PMID- 24330493
TI  - Improving the mechanical properties of multiuse dental floss holders.
AB  - OBJECTIVES: This study was designed to determine the effect of using a tensioning
      device and various winding techniques on the tension of a polytetrafluorethylene
      (PTFE) floss in a multiuse holder. The hypothesis of this study is that the use
      of a tensioning device improves the handling and mechanical properties of floss
      holders. MATERIALS AND METHODS: The floss holder was modified so that four
      different degrees of tension (single-/double-wound; with/without tensioning
      device) were obtained and tested in an in vitro model approximating dental
      proximal contact resistance. The following parameters were measured: (I) the
      force (N) necessary to pass through the proximal contact after the 30th passage,
      (II) the displacement of the floss (mm), (III) the loosening of the floss
      (offset, mm), (IV) the change in distance between the branches (mm). RESULTS: (I)
      passage force. All modifications reached 11 N (median). For the double-wound
      modification using the tensioning device, the smallest displacement (II) was 3.6
      mm; the single-wound modification without the tensioning device had the highest
      displacement (7.6 mm, medians) (III). The offset of all four different
      modifications ranged between 0 and -2 mm (medians). For the modification without
      the tensioning device, there was a difference in offset of -2 mm (single-wound)
      and 0.5 mm (double-wound) (medians). Modifications with the tensioning device did
      not produce any offset differences. (IV) A change in distance between the
      branches between -3 mm and -2 mm, respectively (with the tensioning device), and
      0 mm (without the tensioning device) was observed (median). The results indicated
      that double-wound floss and the use of a tensioning device both lead to a
      constant tension of the floss in the floss holder. CONCLUSIONS: Technical
      modifications such as those shown in this study should improve the mechanical
      properties of multiuse floss holders, which, in turn, could lead to more user
      friendly floss holders and hence to higher user acceptance.

PMID- 24330491
TI  - Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk
      of colorectal cancer.
AB  - BACKGROUND: Genome-wide association studies have identified that genetic variants
      in 8q24 confer susceptibility to colorectal cancer (CRC). Recently, a novel
      lncRNA (PRNCR1) that located in the 8q24 was discovered. Single nucleotide
      polymorphisms (SNPs) in the lncRNAs may influence the process of splicing and
      stability of mRNA conformation, resulting in the modification of its interacting
      partners. We hypothesized that SNPs in the lncRNA PRNCR1 may be related to the
      risk of CRC. METHODS: We conducted a case-control study and genotyped five tag
      SNPs in the lncRNA PRNCR1 in 908 subjects including 313 cases with CRC and 595
      control subjects using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) assay. RESULTS: In overall analyses, we found that the
      rs13252298 and rs1456315 were associated with significantly decreased risks of
      CRC. In stratification analyses, we found that CRC patients carrying the
      rs1456315G were likely to have a tumor size of greater than 5 cm (G vs. A:
      adjusted OR = 1.56, 95% CI: 1.10-2.23). Additionally, patients with the
      rs7007694C and rs16901946G had decreased risks to develop poorly differentiated
      CRC, whereas patients with the rs1456315G had an increased risk to develop poorly
      differentiated CRC. CONCLUSION: These findings suggest that SNPs in the lncRNA
      PRNCR1 may contribute to susceptibility to CRC.

PMID- 24330495
TI  - The bonnie baby: experimentally manipulated temperament affects perceived
      cuteness and motivation to view infant faces.
AB  - Attractive individuals are perceived as having various positive personality
      qualities. Positive personality qualities can in turn increase perceived
      attractiveness. However, the developmental origins of the link between
      attractiveness and personality are not understood. This is important because
      infant attractiveness ('cuteness') elicits caregiving from adults, and infant
      personality ('temperament') shapes caregiving behaviour. While research suggests
      that adults have more positive attitudes towards cuter infants, it is not known
      whether positive infant temperament can increase the perception of infant
      cuteness. We investigated the impact of experimentally established infant
      temperament on adults' perception of cuteness and desire to view individual
      faces. Ataseline, adults rated the cuteness of, and keypressed to view, images of
      unfamiliar infants with neutral facial expressions. Training required adults to
      learn about an infant's 'temperament', through repeated pairing of the neutral
      infant face with positive or negative facial expressions and vocalizations.
      Adults then re-rated the original neutral infant faces. Post-training, there were
      significant changes from baseline: infants who were mostly happy were perceived
      as cuter and adults expended greater effort to view them. Infants who were mostly
      sad were not perceived as cuter and adults expended less effort to view them. Our
      results suggest that temperament has clear consequences for how adults perceive
      'bonnie' babies. Perception of infant cuteness is not based on physical facial
      features alone, and is modifiable through experience. 

PMID- 24330494
TI  - The antiangiogenic activities of ethanolic crude extracts of four Salvia species.
AB  - BACKGROUND: Angiogenesis is one of cancer hallmarks that are required for both
      cancer progression and metastasis. In this study we examined the antiangiogenic
      properties of the ethanolic crude extracts of four Salvia species grown in
      Jordan. METHODS: The direct antiangiogenic activity was evaluated using various
      models: ex vivo rat aortic ring assay, in vitro assessment of HUVEC proliferation
      and migration, and in vivo CAM assay, while we used the changes in the expression
      of HIF-1alpha and VEGF in breast cancer cells (MCF 7) as an indicative for the
      indirect antiangiogenic activity. RESULTS: All four crude extracts showed a
      potential antiangiogenic activity in the rat aortic assay, however two species
      were found to be cytotoxic against Fibroblast cell line (PLF); the finding that
      caused the exclusion of these two extracts from further studies. Of the two
      remaining extracts, S. triloba showed very promising direct and indirect
      antiangiogenic activities. S. triloba inhibited the HUVEC proliferation with an
      IC50 of 90 MUg/mL and HUVEC migration by 82% at 150 MUg/mL. Furthermore, the in
      vivo CAM assay also illustrated the high impact of S. triloba against the newly
      formed vessel in the chicken embryonic membrane. Interestingly, the S. triloba
      inhibited the expression of VEGF at the mRNA and protein and the HIF-1alpha mRNA
      in the MCF 7 breast cancer cells under both normoxic and hypoxic conditions.
      CONCLUSIONS: Taken together, all these findings of the direct and indirect
      angiogenic investigations nominated S. triloba as a highly potent antiangiogenic
      plant that may have chemotherapeutic and/or chemoprevention potentials.

PMID- 24330496
TI  - MAC(EI) and MAC(awake) of sevoflurane in infants with obstructive jaundice.
AB  - BACKGROUND: The aim of this study was to determine whether the MACEI and MACawake
      of sevoflurane in infants with obstructive jaundice are different from that
      observed in nonjaundiced infants. METHODS: Infants scheduled for abdominal
      surgery were recruited into the study. General anesthesia was induced with 8%
      sevoflurane inhaled with 8 l.min(-1) of oxygen via mask, followed by adjustment
      of inspired sevoflurane to the target concentration based on the result in
      previous patient at which laryngoscopy and tracheal intubation were attempted and
      maintained for 15 min. All responses to tracheal intubation were assessed. At the
      end of the procedure, sevoflurane was titrated to the target concentration, which
      was kept constant for 15 min before a standard stimulus was applied to determine
      whether the infant was awake. The Dixon's 'up and down' method was used to
      determine progression of subsequent concentrations. RESULTS: There was no
      significant difference between the MACEI of sevoflurane in infants with
      obstructive jaundice (3.40 +/- 0.21%) and that observed in the control group
      (3.43 +/- 0.18%). But the MACawake of sevoflurane in jaundiced infants (1.00 +/-
      0.15%) was significantly lower than that of nonjaundiced controls (1.40 +/-
      0.21%; P = 0.004); to complement these findings, we reported a negative
      correlation between serum total bilirubin and the probability of awakening (OR =
      0.984, 95% CI is 0.970-0.998, P = 0.028). CONCLUSIONS: The MACawake of
      sevoflurane was reduced in obstructive jaundiced infants compared with
      nonjaundiced controls, whereas there was no significant difference between the
      MACEI of sevoflurane in infants with obstructive jaundice and that observed in
      nonjaundiced infants.

PMID- 24330497
TI  - Phylogenomics of fescue grass-derived fungal endophytes based on selected nuclear
      genes and the mitochondrial gene complement.
AB  - BACKGROUND: Tall fescue and meadow fescue are important as temperate pasture
      grasses, forming mutualistic associations with asexual Neotyphodium endophytes.
      The most frequently identified endophyte of Continental allohexaploid tall fescue
      is Neotyphodium coenophialum, while representatives of two other taxa (FaTG-2 and
      FaTG-3) have been described as colonising decaploid and Mediterranean hexaploid
      tall fescue, respectively. In addition, a recent study identified two other
      putatively novel endophyte taxa from Mediterranean hexaploid and decaploid tall
      fescue accessions, which were designated as uncharacterised Neotyphodium species
      (UNS) and FaTG-3-like respectively. In contrast, diploid meadow fescue mainly
      forms associations with the endophyte taxon Neotyphodium uncinatum, although a
      second endophyte taxon, termed N. siegelii, has also been described. RESULTS:
      Multiple copies of the translation elongation factor 1-a (tefA) and beta-tubulin
      (tub2) 'house-keeping' genes, as well as the endophyte-specific perA gene, were
      identified for each fescue-derived endophyte taxon from whole genome sequence
      data. The assembled gene sequences were used to reconstruct evolutionary
      relationships between the heteroploid fescue-derived endophytes and putative
      ancestral sub-genomes derived from known sexual Epichloe species. In addition to
      the nuclear genome-derived genes, the complete mitochondrial genome (mt genome)
      sequence was obtained for each of the sequenced endophyte, and phylogenetic
      relationships between the mt genome protein coding gene complements were also
      reconstructed. CONCLUSIONS: Complex and highly reticulated evolutionary
      relationships between Epichloe-Neotyphodium endophytes have been predicted on the
      basis of multiple nuclear genes and entire mitochondrial protein-coding gene
      complements, derived from independent assembly of whole genome sequence reads.
      The results are consistent with previous studies while also providing novel
      phylogenetic insights, particularly through inclusion of data from the endophyte
      lineage-specific gene, as well as affording evidence for the origin of
      cytoplasmic genomes. In particular, the results obtained from the present study
      imply the possible occurrence of at least two distinct E. typhina progenitors for
      heteropoid taxa, as well the ancestral contribution of an endophyte species
      distinct from (although related to) contemporary E. baconii to the extant hybrid
      species. Furthermore, the present study confirmed the distinct taxonomic status
      of the newly identified fescue endophyte taxa, FaTG-3-like and UNS, which are
      consequently proposed to be renamed FaTG4 and FaTG5, respectively.

PMID- 24330499
TI  - Response to Barussaud et al.: the magnetic anal sphincter in faecal incontinence,
      is initial success sustained over time?

PMID- 24330498
TI  - Expression of EPHRIN-A1, SCINDERIN and MHC class I molecules in head and neck
      cancers and relationship with the prognostic value of intratumoral CD8+ T cells.
AB  - BACKGROUND: Our group has previously shown that EPHRIN-A1 and SCINDERIN
      expression by tumor cells rendered them resistant to cytotoxic T lymphocyte
      mediated lysis. Whereas the prognostic value of EPHRIN-A1 expression in cancer
      has already been studied, the role of SCINDERIN presence remains to be
      established. In the present work, we investigated the prognosis value of EPHRIN
      A1 and SCINDERIN expression in head and neck carcinomas. In addition, we
      monitored the HLA-class I expression by tumor cells and the presence of tumor
      infiltrating CD8+ T cells to evaluate a putative correlation between these
      factors and the survival prognosis by themselves or related to EPHRIN-A1 and
      SCINDERIN expression. METHODS: Tumor tissue sections of 83 patients with head and
      neck cancer were assessed by immunohistochemistry for the expression of EPHRIN
      A1, SCINDERIN, HLA class I molecules and the presence of CD8+ T cells. RESULTS:
      No significant prognosis value could be attributed to these factors
      independently, despite a tendency of association between EPHRIN-A1 and a worse
      clinical outcome. No prognostic value could be observed when CD8+ T cell tumor
      infiltration was analyzed combined with EPHRIN-A1, SCINDERIN or HLA class I
      expression. CONCLUSION: These results highlight that molecules involved in cancer
      cell resistance to cytotoxic T lymphocytes by themselves are not a sufficient
      criteria for prognosis determination in cancer patients. Other intrinsic or tumor
      microenvironmental features should be considered in prognostic evaluation.

PMID- 24330500
TI  - Effects of global changes on the climatic niche of the tick Ixodes ricinus
      inferred by species distribution modelling.
AB  - BACKGROUND: Global climate change can seriously impact on the epidemiological
      dynamics of vector-borne diseases. In this study we investigated how future
      climatic changes could affect the climatic niche of Ixodes ricinus (Acari,
      Ixodida), among the most important vectors of pathogens of medical and veterinary
      concern in Europe. METHODS: Species Distribution Modelling (SDM) was used to
      reconstruct the climatic niche of I. ricinus, and to project it into the future
      conditions for 2050 and 2080, under two scenarios: a continuous human demographic
      growth and a severe increase of gas emissions (scenario A2), and a scenario that
      proposes lower human demographic growth than A2, and a more sustainable gas
      emissions (scenario B2). Models were reconstructed using the algorithm of
      "maximum entropy", as implemented in the software Maxent 3.3.3e; 4,544 occurrence
      points and 15 bioclimatic variables were used. RESULTS: In both scenarios an
      increase of climatic niche of about two times greater than the current area was
      predicted as well as a higher climatic suitability under the scenario B2 than A2.
      Such an increase occurred both in a latitudinal and longitudinal way, including
      northern Eurasian regions (e.g. Sweden and Russia), that were previously
      unsuitable for the species. CONCLUSIONS: Our models are congruent with the
      predictions of range expansion already observed in I. ricinus at a regional scale
      and provide a qualitative and quantitative assessment of the future climatically
      suitable areas for I. ricinus at a continental scale. Although the use of SDM at
      a higher resolution should be integrated by a more refined analysis of further
      abiotic and biotic data, the results presented here suggest that under future
      climatic scenarios most of the current distribution area of I. ricinus could
      remain suitable and significantly increase at a continental geographic scale.
      Therefore disease outbreaks of pathogens transmitted by this tick species could
      emerge in previous non-endemic geographic areas. Further studies will implement
      and refine present data toward a better understanding of the risk represented by
      I. ricinus to human health.

PMID- 24330501
TI  - Carbon catabolite repression correlates with the maintenance of near invariant
      molecular crowding in proliferating E. coli cells.
AB  - BACKGROUND: Carbon catabolite repression (CCR) is critical for optimal bacterial
      growth, and in bacterial (and yeast) cells it leads to their selective
      consumption of a single substrate from a complex environment. However, the root
      cause(s) for the development of this regulatory mechanism is unknown. Previously,
      a flux balance model (FBAwMC) of Escherichia coli metabolism that takes into
      account the crowded intracellular milieu of the bacterial cell correctly
      predicted selective glucose uptake in a medium containing five different carbon
      sources, suggesting that CCR may be an adaptive mechanism that ensures optimal
      bacterial metabolic network activity for growth. RESULTS: Here, we show that
      slowly growing E. coli cells do not display CCR in a mixed substrate culture and
      gradual activation of CCR correlates with an increasing rate of E. coli cell
      growth and proliferation. In contrast, CCR mutant cells do not achieve fast
      growth in mixed substrate culture, and display differences in their cell volume
      and density compared to wild-type cells. Analyses of transcriptome data from wt
      E. coli cells indicate the expected regulation of substrate uptake and metabolic
      pathway utilization upon growth rate change. We also find that forced transient
      increase of intracellular crowding or transient perturbation of CCR delay cell
      growth, the latter leading to associated cell density-and volume alterations.
      CONCLUSIONS: CCR is activated at an increased bacterial cell growth rate when it
      is required for optimal cell growth while intracellular macromolecular density is
      maintained within a narrow physiological range. In addition to CCR, there are
      likely to be other regulatory mechanisms of cell metabolism that have evolved to
      ensure optimal cell growth in the context of the fundamental biophysical
      constraint imposed by intracellular molecular crowding.

PMID- 24330502
TI  - Childhood asthma and vitamin D deficiency in Turkey: is there cause and effect
      relationship between them?
AB  - BACKGROUND: Epidemiological studies show that vitamin D deficiency and
      insufficiency are common worldwide and associated with many diseases including
      asthma. Our aim was to evaluate vitamin D insufficiency and its clinical
      consequences. METHODS: This cross-sectional study was carried out on 170 children
      consisted of 85 who were asthmatic and 85 who were not, aged 2 to 14 years in
      Tekirdag, Turkey, from September 2009 to May 2010. Children's basal serum D
      vitamin levels were determined, and their eating habits, vitamin D intake,
      exposure to sunlight and use of health services during the previous year were
      investigated. The severity of asthma and levels of asthma control were assessed
      according to the Global Initiative for Asthma guidelines. RESULTS: The difference
      between mean vitamin D levels in the asthmatic group (mean +/- SD) 16.6 +/- 8.5
      ng/mL and the healthy control group (mean +/- SD) 28.2 +/- 19.5 ng/mL was found
      to be statistically significant (p < 0.001). Children in the asthma group had
      less exposure to sunlight and ate a diet less rich in vitamin D (p < 0.001). A
      significant difference was observed between the groups regarding the frequency of
      respiratory tract infections leading to emergency unit admissions and number of
      hospitalizations (p < 0.001). It was also shown that a decrease in vitamin D
      level increased the severity of asthma (p < 0.001) and decreased the frequency of
      controlled asthma (p = 0.010). CONCLUSION: This study has demonstrated the
      correlation between plasma 25 (OH) D levels and childhood asthma. Evidently, this
      relationship being influenced by multiple factors other than vitamin D, further
      studies should be conducted to explore the interrelation between all such
      factors.

PMID- 24330503
TI  - Local adaptation to salinity in the three-spined stickleback?
AB  - Different lines of evidence suggest that the occurrence and extent of local
      adaptation in high gene flow marine environments - even in mobile and long-lived
      vertebrates with complex life cycles - may be more widespread than earlier
      thought. We conducted a common garden experiment to test for local adaptation to
      salinity in Baltic Sea sticklebacks (Gasterosteus aculeatus). Fish from three
      different native salinity regimes (high, mid and low) were subjected to three
      salinity treatments (high, mid and low) in a full-factorial experimental design.
      Irrespective of their origin, fish subjected to low (and mid) salinity treatments
      exhibited higher juvenile survival, grew to largest sizes and were in better
      condition than fish subjected to the high salinity treatment. However, a
      significant interaction between native and treatment salinities - resulting
      mainly from the poor performance of fish native to low salinity in the high
      salinity treatment - provided clear cut evidence for adaptation to local
      variation in salinity. Additional support for this inference was provided by the
      fact that the results concur with an earlier demonstration of significant
      differentiation in a number of genes with osmoregulatory functions across the
      same populations and that the population-specific responses to salinity
      treatments exceeded that to be expected by random genetic drift. 

PMID- 24330505
TI  - A cluster randomised controlled trial of the Climate Schools: Ecstasy and
      Emerging Drugs Module in Australian secondary schools: study protocol.
AB  - BACKGROUND: The use of ecstasy is a public health problem and is associated with
      a range of social costs and harms. In recent years, there has been growing
      concern about the availability and misuse of new and emerging drugs designed to
      mimic the effects of illicit drugs, including ecstasy. This, coupled with the
      fact that the age of use and the risk factors for using ecstasy and emerging
      drugs are similar, provides a compelling argument to implement prevention for
      these substances simultaneously. The proposed study will evaluate whether a
      universal Internet-based prevention program, known as the Climate Schools:
      Ecstasy and Emerging Drugs Module, can address and prevent the use of ecstasy and
      emerging drugs among adolescents. METHODS: A cluster randomised controlled trial
      will be conducted among Year 10 students (aged 15-16 years) from 12 secondary
      schools in Sydney, Australia. Schools will be randomly assigned to either the
      Climate Schools intervention group or the control group. All students will
      complete a self-report questionnaire at baseline, immediately post-intervention,
      and 6-, 12- and 24-months post-baseline. The primary outcome measures will
      include ecstasy and emerging drug-related knowledge, intentions to use these
      substances in the future, and the patterns of use of ecstasy and emerging drugs.
      A range of secondary outcomes will also be assessed, including beliefs and
      attitudes about ecstasy and emerging drugs, peer pressure resistance, other
      substance use and mental health outcomes. DISCUSSION: To our knowledge, this will
      be the first evaluation of an Internet-based program designed to specifically
      target ecstasy and NED use among adolescents. If deemed effective, the Climate
      Schools: Ecstasy and Emerging Drugs Module will provide schools with an
      interactive and novel prevention program for ecstasy and emerging drugs that can
      be readily implemented by teachers. TRIAL REGISTRATION: This trial is registered
      with the Australian New Zealand Clinical Trials Registry, ACTRN12613000708752.

PMID- 24330504
TI  - Cardiomyopathy reverses with recovery of liver injury, cholestasis and cholanemia
      in mouse model of biliary fibrosis.
AB  - BACKGROUND: Triggers and exacerbants of cirrhotic cardiomyopathy (CC) are poorly
      understood, limiting treatment options in patients with chronic liver diseases.
      Liver transplantation alone reverses some features of CC, but the physiology
      behind this effect has never been studied. AIMS: We aimed to determine whether
      reversal of liver injury and fibrosis in mouse affects cardiac parameters. The
      second aim was to determine whether cardiomyopathy can be induced by specifically
      increasing systemic bile acid (BA) levels. METHODS: 6-8 week old male C57BL6J
      mice were fed either chow (n = 5) or 3,5-diethoxycarbonyl-1,4-dihydroxychollidine
      (DDC) (n = 10) for 3 weeks. At the end of 3 weeks, half the mice in the DDC fed
      group were randomized to chow (the reversed [REV] group). Serial ECHOs and
      electrocardiographic analysis was conducted weekly for 6 weeks followed by liver
      tissue and serum studies. Hearts were analysed for key components of function and
      cell signalling. Cardiac physiological and molecular parameters were similarly
      analysed in Abcb11(-/-) mice (n = 5/grp) fed 0.5% cholic acid supplemented diet
      for 1 week. RESULTS: Mice in the REV group showed normalization of biochemical
      markers of liver injury with resolution of electrocardiographic and ECHO
      aberrations. Catecholamine resistance seen in DDC group resolved in the REV
      group. Cardiac recovery was accompanied by normalization of cardiac troponin-T2
      as well as resolution of cardiac stress response at RNA level. Cardiovascular
      physiological and molecular parameters correlated with degree of cholanemia.
      Cardiomyopathy was reproduced in cholanemic BA fed Abcb11(-/-) mice. CONCLUSIONS:
      Cardiomyopathy resolves with resolution of liver injury, is associated with
      cholanaemia, and can be induced by BA feeding.

PMID- 24330506
TI  - Schmallenberg Virus beyond Latitude 65 degrees N.
AB  - Extensive and rapid spread of Schmallenberg virus (SBV) in Sweden was detected by
      consecutive serological bulk milk surveys conducted before and after the vector
      season of 2012. Whereas <0.2% of cattle herds tested positive in a first survey
      in spring 2012, SBV-specific antibodies were detected in almost 75% of 723 bulk
      milk samples randomly collected all over the country 6 months later, beyond the
      65th northern latitude, and with an observed spatial distribution suggesting
      multiple introductions of the virus. Circulation of virus was later confirmed by
      the detection of SBV in malformed lambs and calves starting from November 2012
      and January 2013, respectively. These observations suggest SBV circulation
      starting from July 2012, with a peak in transmission between August and October.
      A local heterogeneity of within-herd seroprevalence was found, indicating that
      SBV-naive animals remain also in highly infected areas enabling the re-emergence
      of the infection in the coming vector season.

PMID- 24330507
TI  - Genome sequencing: a systematic review of health economic evidence.
AB  - Recently the sequencing of the human genome has become a major biological and
      clinical research field. However, the public health impact of this new technology
      with focus on the financial effect is not yet to be foreseen. To provide an
      overview of the current health economic evidence for genome sequencing, we
      conducted a thorough systematic review of the literature from 17 databases. In
      addition, we conducted a hand search. Starting with 5 520 records we ultimately
      included five full-text publications and one internet source, all focused on cost
      calculations. The results were very heterogeneous and, therefore, difficult to
      compare. Furthermore, because the methodology of the publications was quite poor,
      the reliability and validity of the results were questionable. The real costs for
      the whole sequencing workflow, including data management and analysis, remain
      unknown. Overall, our review indicates that the current health economic evidence
      for genome sequencing is quite poor. Therefore, we listed aspects that needed to
      be considered when conducting health economic analyses of genome sequencing.
      Thereby, specifics regarding the overall aim, technology, population, indication,
      comparator, alternatives after sequencing, outcomes, probabilities, and costs
      with respect to genome sequencing are discussed. For further research, at the
      outset, a comprehensive cost calculation of genome sequencing is needed, because
      all further health economic studies rely on valid cost data. The results will
      serve as an input parameter for budget-impact analyses or cost-effectiveness
      analyses. 

PMID- 24330508
TI  - World AIDS day commemoration.

PMID- 24330509
TI  - Share with women. Nitrous oxide for pain relief in labor.

PMID- 24330510
TI  - Disease burden of herpes zoster in Sweden--predominance in the elderly and in
      women - a register based study.
AB  - BACKGROUND: The herpes zoster burden of disease in Sweden is not well
      investigated. There is no Swedish immunization program to prevent varicella
      zoster virus infections. A vaccine against herpes zoster and its complications is
      now available. The aim of this study was to estimate the herpes zoster burden of
      disease and to establish a pre-vaccination baseline of the minimum incidence of
      herpes zoster. METHODS: Data were collected from the Swedish National Health Data
      Registers including the Patient Register, the Pharmacy Register, and the Cause of
      Death Register. The herpes zoster burden of disease in Sweden was estimated by
      analyzing the overall, and age and gender differences in the antiviral
      prescriptions, hospitalizations and complications during 2006-2010 and mortality
      during 2006-2009. RESULTS: Annually, 270 per 100,000 persons received antiviral
      treatment for herpes zoster, and the prescription rate increased with age. It was
      approximately 50% higher in females than in males in the age 50+ population (rate
      ratio 1.39; 95% CI, 1.22 to 1.58). The overall hospitalization rate for herpes
      zoster was 6.9/100,000 with an approximately three-fold increase for patients
      over 80 years of age compared to the age 70-79 group. A gender difference in
      hospitalization rates was observed: 8.1/100,000 in females and 5.6/100,000 in
      males. Herpes zoster, with a registered complication, was found in about one
      third of the hospitalized patients and the most common complications involved the
      peripheral and central nervous systems. Death due to herpes zoster was a rare
      event. CONCLUSIONS: The results of this study demonstrate the significant burden
      of herpes zoster disease in the pre-zoster vaccination era. A strong correlation
      with age in the herpes zoster- related incidence, hospitalization, complications,
      and mortality rates was found. In addition, the study provides further evidence
      of the female predominance in herpes zoster disease.

PMID- 24330511
TI  - An efficient magnetically modified microbial cell biocomposite for carbazole
      biodegradation.
AB  - Magnetic modification of microbial cells enables to prepare smart biocomposites
      in bioremediation. In this study, we constructed an efficient biocomposite by
      assembling Fe3O4 nanoparticles onto the surface of Sphingomonas sp. XLDN2-5
      cells. The average particle size of Fe3O4 nanoparticles was about 20 nm with 45.5
      emu g-1 saturation magnetization. The morphology of Sphingomonas sp. XLDN2-5
      cells before and after Fe3O4 nanoparticle loading was verified by scanning
      electron microscopy and transmission electronic microscopy. Compared with free
      cells, the microbial cell/Fe3O4 biocomposite had the same biodegradation activity
      but exhibited remarkable reusability. The degradation activity of the microbial
      cell/Fe3O4 biocomposite increased gradually during recycling processes.
      Additionally, the microbial cell/Fe3O4 biocomposite could be easily separated and
      recycled by an external magnetic field due to the super-paramagnetic properties
      of Fe3O4 nanoparticle coating. These results indicated that magnetically modified
      microbial cells provide a promising technique for improving biocatalysts used in
      the biodegradation of hazardous compounds. 

PMID- 24330512
TI  - Gold nanoparticles: recent aspects for human toxicology.
AB  - Nanoparticles (particles sized between 1 and 100 nanometers) are more and more
      used in all fields of science and medicine for their physicochemical properties.
      As gold has traditionally been considered as chemically inert and biocompatible,
      in particular, gold nanoparticles have been established as valuable tools in
      several areas of biomedical research. But in contrast to the multitude of studies
      that addressed the clinical use of gold nanoparticles, only little is known about
      potential toxicological effects such as induction of inflammatory immune
      responses, possible apoptotic cell death or developmental growth inhibition in
      embryos. Therefore the present study performed a systematic review of
      toxicological data, especially experimentally acquired data concerning in-vivo
      toxicity, published in the PubMed. It can be stated that the data in this area of
      research is still largely limited. Especially, knowledge about size-, charge- and
      surface-chemistry dependent in-vivo-toxicity is needed to predict the hazard
      potential of auric nanoparticles (AuNPs) for humans. 

PMID- 24330513
TI  - FOLFIRI as a second-line therapy in patients with docetaxel-pretreated gastric
      cancer: a historical cohort.
AB  - BACKGROUND: The role of second-line therapy in gastric cancer patients mostly
      stemmed from clinical trials with monochemotherapy carried out in Asian
      countries. Nevertheless, these results cannot be broadly generalized as molecular
      studies suggested the existence of different sets of deregulated gene networks
      correlated with ethnicity. In the present study, we investigated the activity and
      safety of FOLFIRI given as a second-line therapy in metastatic gastric or gastro
      esophageal junction cancer patients who experienced disease progression on or
      after first-line docetaxel-containing chemotherapy. METHODS: Patients with
      histologically confirmed metastatic gastric cancer who failed docetaxel
      containing first-line therapy and who received FOLFIRI in second line were
      eligible for the study. Seventy patients treated at three Italian cancer centers
      between 2005 and 2012 entered the study. Patients received every 2 weeks
      irinotecan 180 mg/m2 as 1 h infusion on day 1, folinic acid 100 mg/m2
      intravenously days 1-2, and fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2
      continuous infusion over 22 hours days 1-2. RESULTS: We observed 1(1.4%) complete
      response, 15 (21.4%) partial response, for an overall response rate of 22.8% (95%
      confidence interval (CI): 13.4-32.3). Stable disease was recorded in 21 (30%)
      patients. Median progression-free survival and overall survival were 3.8 months
      (95% CI: 3.3-4.4) and 6.2 months (95% CI: 5.3-7.1), respectively. The treatment
      was well tolerated, as the most common G3-4 toxicities were neutropenia (28.5%)
      and diarrhea (14.5%). CONCLUSIONS: FOLFIRI appears an effective and safe
      treatment option for pretreated metastatic gastric cancer patients, and deserves
      further investigation in randomized clinical trials.

PMID- 24330514
TI  - Investigation of the relationship between serum hormones and pilonidal sinus
      disease: a cross-sectional study.
AB  - AIM: The aim of this cross-sectional study was to determine whether pilonidal
      sinus is influenced by hormones that stimulate body hair growth. Currently, there
      are insufficient data on the presence of hormonal abnormalities in pilonidal
      sinus disease. METHOD: Hormone levels (including those of thyroid-stimulating
      hormone, follicular-stimulating hormone, luteinizing hormone, prolactin,
      progesterone, oestradiol, testosterone, cortisol and dehydroepiandrosterone) were
      measured in 39 patients with pilonodal sinus presenting between February 2013 and
      March 2013. The results were compared with those of 39 volunteers without this
      disease. RESULTS: There was no statistically significant difference between men
      with pilonidal sinus disease (P > 0.05). The prolactin levels of women with
      pilonoidal sinus were significantly higher than those of women in the control
      group (P < 0.05). CONCLUSION: Raised serum prolactin levels in women may be
      related to the development of pilonidal sinus disease.

PMID- 24330515
TI  - In-VITRo effect of Ficus deltoidea on the contraction of isolated rat's uteri is
      mediated via multiple receptors binding and is dependent on extracellular
      calcium.
AB  - BACKGROUND: Ficus deltoidea, is a perennial herb that is used to assist labor,
      firm the uterus post-delivery and to prevent postpartum bleeding. In view of its
      claimed uterotonic action, the mechanisms underlying plant's effect on uterine
      contraction were investigated. METHODS: Adult female SD rats were injected with 2
      mg/kg 17beta-oestradiol (E2) to synchronize their oestrous cycle. A day after
      injection, uteri were removed for in-vitro contraction studies. The dose
      dependent effect of Ficus deltoidea aqeous extract (FDA) on the tension produced
      by the isolated rat's uteri was determined. The effects of atropine (2*10(-8) M),
      atosiban (0.5 IU), THG113.31 (10 MUM), oxodipine (0.25 mM), EDTA (1 mM), 2-amino
      ethoxy-diphenylborate (2-APB) (40 mM) and thapsigargin (1 mM) on the maximum
      force of contraction (Emax) achieved following 2 mg/ml FDA administration were
      also investigated. RESULTS: FDA induced in-vitro contraction of the isolated
      rat's uteri in a dose-dependent manner. Administration of atropine, atosiban and
      THG113.31 reduced the Emax with atosiban having the greatest effect. The Emax was
      also reduced following oxodipine and EDTA administration. There was no
      significant change observed following 2-APB administration. Thapsigargin,
      however, augmented Emax. CONCLUSIONS: FDA-induced contraction of the isolated
      rat's uteri is mediated via multiple uterotonin receptors (muscarinic, oxytocin
      and prostaglandin F2alpha) and was dependent on the extracellular Ca2+.
      Contraction, however, was not dependent on the Ca2+ release from the internal
      stores. This in-vitro study provides the first scientific evidence on the claimed
      effect of Ficus Deltoidea on uterine contraction.

PMID- 24330516
TI  - The long term effectiveness and cost-effectiveness of initiating treatment for
      ocular hypertension.
AB  - PURPOSE: To investigate the long-term health and economic consequences of direct
      treatment initiation in ocular hypertension patients. METHODS: A cost
      effectiveness analysis with a societal perspective and a lifelong horizon was
      performed. The primary outcomes were the incremental quality-adjusted life years
      (QALYs) and costs of direct pressure-lowering treatment for ocular hypertension,
      compared to a strategy where treatment is postponed until conversion to glaucoma
      has been observed. We used a decision analytic model based on individual patient
      simulation to forecast disease progression and treatment decisions in both
      strategies in a representative heterogeneous patient population and in 18 patient
      subgroups stratified by initial intraocular pressure and additional risk factors
      for conversion. RESULTS: The incremental discounted health gain of direct
      treatment was 0.27 QALYs, whereas the incremental discounted costs were -? 649
      during an average lifetime of 26 years. In the simulations of patient subgroups,
      the model outcomes moved towards higher health gains and lower incremental costs
      with increasing risk of conversion in the patient population. The incremental
      cost-effectiveness ratio of direct treatment ranged from ? 15,425 per QALY gained
      in the lowest-risk subgroup to dominance in the highest-risk subgroup.
      Probabilistic sensitivity analysis indicated that uncertainty surrounding the
      model input parameters did not affect the conclusions. CONCLUSION: Direct, early,
      pressure-lowering treatment is a dominant cost-effective treatment strategy over
      a strategy to start the same treatment approach later, after glaucoma has
      occurred for patients with ocular hypertension. Its implementation and
      consequences should be discussed with ophthalmologists and individual patients.

PMID- 24330517
TI  - Host serum miR-223 is a potential new biomarker for Schistosoma japonicum
      infection and the response to chemotherapy.
AB  - BACKGROUND: Numerous studies have shown that aberrant microRNA (miRNA) expression
      is associated with the pathogenesis and progression of various human diseases.
      Hence, serum miRNAs are considered to be potential biomarkers for the diagnosis
      of human diseases. This study examined whether several miRNAs known to be
      commonly deregulated in liver diseases are deregulated in the serum of hosts with
      hepatic schistosomiasis, and thus whether they could serve as potential markers
      for detection of schistosome infection and evaluation of the effectiveness of
      chemotherapy. METHODS: We analyzed the serum levels of six selected candidate
      miRNA molecules (miR-146b, miR-122, miR-223, miR-199a-5p, miR-199a-3p, miR-34a)
      from mice, rabbits, buffalos and humans infected with Schistosoma japonicum using
      qPCR. We evaluated liver pathology by determining the hydroxyproline content in
      liver tissues. Primary resident liver cells were isolated to quantify the
      expression level of deregulated miRNAs. Bioinformatics analyses were also
      conducted to assess the potential function of miR-223. RESULTS: Using a mouse
      model of Schistosoma japonicum infection, we found that the expression level of
      serum miR-223 was significantly elevated after infection, but returned to near
      normal levels after the treatment with praziquantel (PZQ). Importantly, the level
      of serum miR-223 reflected the extent of liver pathology post-infection. We
      validated the elevated level of the circulating miR-223 in serum samples of other
      host species including rabbits, buffalos and humans. In addition, our results
      showed that miR-223 was primarily located in the Kupffer cells, but its
      expression levels were significantly up-regulated in hepatocytes, hepatic
      stellate cells and Kupffer cells after infection. Bioinformatics analyses
      revealed a potential functional role of miR-223 in transcription regulator
      activity, transcription factor activity and DNA binding. CONCLUSIONS: This study
      suggested that the circulating miR-223 could serve as a potential new biomarker
      for the detection of schistosome infection and the assessment of the response to
      chemotherapy.

PMID- 24330518
TI  - The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity
      via direct binding.
AB  - BACKGROUND: The WW domain containing protein WWOX has been postulated to behave
      as a tumor suppressor in breast and other cancers. Expression of this protein is
      lost in over 70% of ER negative tumors. This prompted us to investigate the
      phenotypic and gene expression effects of loss of WWOX expression in breast
      cells. METHODS: Gene expression microarrays and standard in vitro assays were
      performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic
      analyses were used to identify gene networks and transcriptional regulators
      affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used
      to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays,
      ChIP, confocal microscopy and in silico analyses were employed to determine the
      effect of WWOX silencing on TGFbeta-signaling. RESULTS: WWOX silencing affected
      cell proliferation, motility, attachment and deregulated expression of genes
      involved in cell cycle, motility and DNA damage. Interestingly, we detected an
      enrichment of targets activated by the SMAD3 transcription factor, including
      significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts.
      Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3
      via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3
      occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches
      activation of a TGFbeta responsive reporter. Additionally, WWOX expression leads
      to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since
      the TGFbeta target ANGPTL4 plays a key role in lung metastasis development, we
      performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray
      datasets from breast carcinomas. We observed a significant inverse correlation
      between WWOX and ANGPTL4. Furthermore, the WWOX(lo)/ANGPTL4(hi) cluster of breast
      tumors is enriched in triple-negative and basal-like sub-types. Tumors with this
      gene expression signature could represent candidates for anti-TGFbeta targeted
      therapies. CONCLUSIONS: We show for the first time that WWOX modulates SMAD3
      signaling in breast cells via direct WW-domain mediated binding and potential
      cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression
      increases with breast cancer progression and it behaves as an inhibitor of SMAD3
      transcriptional activity these observations may help explain, at least in part,
      the paradoxical pro-tumorigenic effects of TGFbeta signaling in advanced breast
      cancer.

PMID- 24330519
TI  - Little evidence of a role for the alpha1GABAA subunit-containing receptor in a
      rhesus monkey model of alcohol drinking.
AB  - BACKGROUND: Alcohol potentiates GABAergic neurotransmission via action at the
      GABAA receptor. alpha1 subunit-containing GABAA receptors have been implicated as
      mediators, in part, of the behavioral and abuse-related effects of alcohol in
      rodents. METHODS: We systematically investigated the effects of 1 alpha1
      preferring benzodiazepine agonist, zolpidem, and 2 antagonists, beta-carboline-3
      carboxylate-tert-butyl ester (betaCCT) and 3-propoxy-beta-carboline hydrochloride
      (3-PBC), on oral self-administration of alcohol (2% w/v) or sucrose solution and
      observable behavior in rhesus macaques. We compared these effects to those of the
      nonselective benzodiazepine agonist triazolam, antagonist flumazenil, and inverse
      agonist beta-carboline carboxylate (betaCCE). RESULTS: Alcohol and sucrose
      solutions maintained reliable baseline drinking behavior across the study. The
      alpha1-preferring compounds did not affect intake, number of sipper extensions,
      or blood alcohol levels (BALs) at any of the doses tested. Zolpidem, betaCCT, and
      3-PBC increased latency to first sipper extension in animals self-administering
      alcohol, but not sucrose, solution. Triazolam exerted biphasic effects on alcohol
      drinking behavior, increasing intake at low doses but decreasing BAL and
      increasing latency at higher doses. At doses higher than those effective in
      alcohol-drinking animals, triazolam increased sucrose intake and latency.
      Flumazenil nonsystematically increased number of extensions for alcohol but
      decreased BAL, with no effects on sucrose drinking. betaCCE decreased sipper
      extensions for alcohol and increased latency for first sucrose sipper extension,
      but full dose-effect relationships could not be determined due to seizures at
      higher doses. CONCLUSIONS: Alcohol-drinking animals appeared more sensitive to
      the effects of GABAergic compounds on drinking behavior. However, these results
      do not support a strong contribution of alpha1GABAA receptors to the reinforcing
      effects of alcohol in primates.

PMID- 24330520
TI  - Cross-sex hormonal treatment and body uneasiness in individuals with gender
      dysphoria.
AB  - INTRODUCTION: Cross-sex hormonal treatment (CHT) used for gender dysphoria (GD)
      could by itself affect well-being without the use of genital surgery; however, to
      date, there is a paucity of studies investigating the effects of CHT alone. AIMS:
      This study aimed to assess differences in body uneasiness and psychiatric
      symptoms between GD clients taking CHT and those not taking hormones (no CHT). A
      second aim was to assess whether length of CHT treatment and daily dose provided
      an explanation for levels of body uneasiness and psychiatric symptoms. METHODS: A
      consecutive series of 125 subjects meeting the criteria for GD who not had
      genital reassignment surgery were considered. MAIN OUTCOME MEASURES: Subjects
      were asked to complete the Body Uneasiness Test (BUT) to explore different areas
      of body-related psychopathology and the Symptom Checklist-90 Revised (SCL-90-R)
      to measure psychological state. In addition, data on daily hormone dose and
      length of hormonal treatment (androgens, estrogens, and/or antiandrogens) were
      collected through an analysis of medical records. RESULTS: Among the male-to
      female (MtF) individuals, those using CHT reported less body uneasiness compared
      with individuals in the no-CHT group. No significant differences were observed
      between CHT and no-CHT groups in the female-to-male (FtM) sample. Also, no
      significant differences in SCL score were observed with regard to gender (MtF vs.
      FtM), hormone treatment (CHT vs. no-CHT), or the interaction of these two
      variables. Moreover, a two-step hierarchical regression showed that cumulative
      dose of estradiol (daily dose of estradiol times days of treatment) and
      cumulative dose of androgen blockers (daily dose of androgen blockers times days
      of treatment) predicted BUT score even after controlling for age, gender role,
      cosmetic surgery, and BMI. CONCLUSIONS: The differences observed between MtF and
      FtM individuals suggest that body-related uneasiness associated with GD may be
      effectively diminished with the administration of CHT even without the use of
      genital surgery for MtF clients. A discussion is provided on the importance of
      controlling both length and daily dose of treatment for the most effective impact
      on body uneasiness.

PMID- 24330521
TI  - Diversity and history of the long-chain acyl-CoA synthetase (Acsl) gene family in
      vertebrates.
AB  - BACKGROUND: Fatty acids, a considerable fraction of lipid molecules, participate
      in fundamental physiological processes. They undergo activation into their
      corresponding CoA esters for oxidation or esterification into complex lipids
      (e.g. triglycerides, phospholipids and cholesterol esters), a process that is
      carried out by acyl-CoA synthases (ACS). Here we analyze the evolution of the
      gene family encoding for the long-chain acyl-CoA synthetases (Acsl) in
      vertebrates. RESULTS: By means of phylogenetics and comparative genomics we show
      that genome duplications (2R) generated the diversity of Acsl genes in extant
      vertebrate lineages. In the vertebrate ancestor two separate genes originated the
      current Acsl1/5/6 and the Acsl3/4 gene families, and the extra gene duplicates in
      teleosts are a consequence of the teleost specific third round of genome
      duplication (3R). Moreover, the diversity of Acsl family members is broader than
      anticipated. Our strategy uncovered a novel uncharacterized Acsl-like gene found
      in teleosts, spotted gar, coelacanth and possibly lamprey, which we designate
      Acsl2. The detailed analysis of the Acsl2 teleost gene locus strongly supports
      the conclusion that it corresponds to a retained 2R paralogue, lost in tetrapods.
      CONCLUSIONS: We provide here the first evolutionary analysis of the Acsl gene
      family in vertebrates, showing the specific contribution of 2R/3R to the
      diversity of this gene family. We find also that the division of ACSL enzymes
      into two groups predates at least the emergence of deuterostomes. Our study
      indicates that genome duplications significantly contributed to the elaboration
      of fatty acid activation metabolism in vertebrates.

PMID- 24330522
TI  - Rift valley Fever in Kruger national park: do buffalo play a role in the inter
      epidemic circulation of virus?
AB  - Rift Valley fever (RVF) is a zoonotic mosquito-borne virus disease of livestock
      and wild ruminants that has been identified as a risk for international spread.
      Typically, the disease occurs in geographically limited outbreaks associated with
      high rainfall events and can cause massive losses of livestock. It is unclear how
      RVF virus persists during inter-epidemic periods but cryptic cycling of the virus
      in wildlife populations may play a role. We investigated the role that free
      living African buffalo (Syncerus caffer caffer) might play in inter-epidemic
      circulation of the virus and looked for geographic, age and sex patterns of Rift
      Valley fever virus (RVFV) infection in African buffalo. Buffalo serum samples
      were collected (n = 1615) in Kruger National Park (KNP), South Africa, during a
      period of 1996-2007 and tested for antibodies to RVF. We found that older animals
      were more likely to be seropositive for anti-RVFV antibody than younger animals,
      but sex was not correlated with the likelihood of being anti-RVFV antibody
      positive. We also found geographic variation within KNP; herds in the south were
      more likely to have acquired anti-RVFV antibody than herds farther north - which
      could be driven by host or vector ecology. In all years of the study between 1996
      and 2007, we found young buffalo (under 2 years of age) that were seropositive
      for anti-RVFV antibody, with prevalence ranging between 0 and 27% each year,
      indicating probable circulation. In addition, we also conducted a 4-year
      longitudinal study on 227 initially RVFV seronegative buffalo to look for
      evidence of seroconversion outside known RVF outbreaks within our study period
      (2008-2012). In the longitudinal study, we found five individuals that
      seroconverted from anti-RVFV antibody negative to anti-RVFV antibody positive,
      outside of any detected outbreak. Overall, our results provide evidence of long
      term undetected circulation of RVFV in the buffalo population. 

PMID- 24330523
TI  - Effective postoperative pain management in children after ambulatory surgery,
      with a focus on tonsillectomy: barriers and possible solutions.
AB  - Pain following ambulatory surgery is often poorly managed at home. Certain
      procedures, such as tonsillectomy, cause high levels of pain for at least 1 week
      postoperatively. This impacts significantly on recovery and postoperative
      morbidity with regards to oral intake, sleep, and behavior. Barriers to effective
      postoperative pain management at home following discharge have been investigated
      and incorporate: parental factors, such as the ability to recognize and assess
      their child's pain, and misconceptions about analgesics; child factors, such as
      refusal to take medication; medication factors, such as ineffective medication or
      inadequate formulation or dose of analgesics; and system factors, such as poor
      discharge instructions, difficulty in obtaining medication and lack of
      information provision. A number of interventions have been suggested and trialled
      in an effort to address these barriers, which encompass educational strategies,
      improved information provision, improved medication regimens, and the provision
      of tools to aid parents in the pain management of their children. All in all,
      improvements in pain outcomes have been minor, and a more holistic approach, that
      appreciates the complex and multifaceted nature of pain management at home, is
      required. 

PMID- 24330524
TI  - Space electric field concentrated effect for Zr:SiO2 RRAM devices using porous
      SiO2 buffer layer.
AB  - To improve the operation current lowing of the Zr:SiO2 RRAM devices, a space
      electric field concentrated effect established by the porous SiO2 buffer layer
      was investigated and found in this study. The resistive switching properties of
      the low-resistance state (LRS) and high-resistance state (HRS) in resistive
      random access memory (RRAM) devices for the single-layer Zr:SiO2 and bilayer
      Zr:SiO2/porous SiO2 thin films were analyzed and discussed. In addition, the
      original space charge limited current (SCLC) conduction mechanism in LRS and HRS
      of the RRAM devices using bilayer Zr:SiO2/porous SiO2 thin films was found.
      Finally, a space electric field concentrated effect in the bilayer Zr:SiO2/porous
      SiO2 RRAM devices was also explained and verified by the COMSOL Multiphysics
      simulation model. 

PMID- 24330525
TI  - Differences between patients with chronic widespread pain and local chronic low
      back pain in primary care--a comparative cross-sectional analysis.
AB  - BACKGROUND: Chronic pain is a common reason for consultation in general practice.
      Current research distinguishes between chronic localized pain (CLP) and chronic
      widespread pain (CWP). The aim of this study was to identify differences between
      CWP and chronic low back pain (CLBP), a common type of CLP, in primary care
      settings. METHODS: Fifty-eight German general practitioners (GPs) consecutively
      recruited all eligible patients who consulted for chronic low back pain during a
      5-month period. All patients received a questionnaire on sociodemographic data,
      pain characteristics, comorbidities, psychosomatic symptoms, and previous
      therapies. RESULTS: GPs recruited 647 eligible patients where of a quarter (n =
      163, 25.2%) met the CWP criteria according to the American College of
      Rheumatology. CWP patients had significantly more comorbidities and psychosomatic
      symptoms, showed longer pain duration, and suffered predominantly from permanent
      pain instead of distinguishable pain attacks. CWP patients were more often
      females, are less working and reported a current pension application or a state
      approved grade of disability more frequently. We found no other differences in
      demographic parameters such as age, nationality, marital status, number of
      persons in household, education, health insurance status, or in health care
      utilization data. CONCLUSIONS: This project is the largest study performed to
      date which analyzes differences between CLBP and CWP in primary care settings.
      Our results showed that CWP is a frequent and particularly severe pain syndrome.
      TRIAL REGISTRATION: German Clinical Trial Register, DRKS00003123.

PMID- 24330526
TI  - Synthesis and biological characterisation of 18F-SIG343 and 18F-SIG353, novel and
      high selectivity sigma2 radiotracers, for tumour imaging properties.
AB  - BACKGROUND: Sigma2 (sigma2) receptors are highly expressed in cancer cell lines
      and in tumours. Two novel selective 18F-phthalimido sigma2 ligands, 18F-SIG343
      and 18F-SIG353, were prepared and characterised for their potential tumour
      imaging properties. METHODS: Preparation of 18F-SIG343 and 18F-SIG353 was
      achieved via nucleophilic substitution of their respective nitro precursors. In
      vitro studies including radioreceptor binding assays in the rat brain membrane
      and cell uptake studies in the A375 cell line were performed. In vivo studies
      were carried out in mice bearing A375 tumours including positron emission
      tomography (PET) imaging, biodistribution, blocking and metabolite studies.
      RESULTS: In vitro studies showed that SIG343 and SIG353 displayed excellent
      affinity and selectivity for sigma2 receptors (Ki(sigma2) = 8 and 3 nM,
      sigma2:sigma1 = 200- and 110-fold, respectively). The sigma2 selectivity of 18F
      SIG343 was further confirmed by blocking studies in A375 cells, however, not
      noted for 18F-SIG353. Biodistribution studies showed that both radiotracers had
      similar characteristics including moderately high tumour uptake (4%ID/g to
      5%ID/g); low bone uptake (3%ID/g to 4%ID/g); and high tumour-to-muscle uptake
      ratios (four- to sevenfold) up to 120 min. Although radiotracer uptake in organs
      known to express sigma receptors was significantly blocked by pre-injection of
      competing sigma ligands, the blocking effect was not observed in the tumour. PET
      imaging studies indicated major radioactive localisation in the chest cavity for
      both ligands, with approximately 1%ID/g uptake in the tumour at 120 min.
      Metabolite studies showed that the original radiotracers remained unchanged 65%
      to 80% in the tumour up to 120 min. CONCLUSIONS: The lead ligands showed
      promising in vitro and in vivo characteristics. However, PET imaging indicated
      low tumour-to-background ratios. Furthermore, we were unable to demonstrate that
      uptake in the A375 tumour was sigma2-specific. 18F-SIG343 and 18F-SIG343 do not
      display ideal properties for imaging the sigma2 receptor in the A375 tumour
      model. However, since the radiotracers show promising in vitro and in vivo
      characteristics, longer scans using appropriate half-life isotopes and
      alternative tumour models will be carried out in future studies to fully validate
      the imaging characteristics of these radiotracers.

PMID- 24330527
TI  - Women's responses to changes in U.S. Preventive Task Force's mammography
      screening guidelines: results of focus groups with ethnically diverse women.
AB  - BACKGROUND: The 2009 U.S. Preventive Services Task Force (USPSTF) changed
      mammography guidelines to recommend routine biennial screening starting at age
      50. This study describes women's awareness of, attitudes toward, and intention to
      comply with these new guidelines. METHODS: Women ages 40-50 years old were
      recruited from the Boston area to participate in focus groups (k = 8; n = 77).
      Groups were segmented by race/ethnicity (Caucasian = 39%; African American = 35%;
      Latina = 26%), audio-taped, and transcribed. Thematic content analysis was used.
      RESULTS: Participants were largely unaware of the revised guidelines and
      suspicious that it was a cost-savings measure by insurers and/or providers. Most
      did not intend to comply with the change, viewing screening as obligatory. Few
      felt prepared to participate in shared decision-making or advocate for their
      preferences with respect to screening. CONCLUSIONS: Communication about the
      rationale for mammography guideline changes has left many women unconvinced about
      potential disadvantages or limitations of screening. Since further guideline
      changes are likely to occur with advances in technology and science, it is
      important to help women become informed consumers of health information and
      active participants in shared decision-making with providers. Additional research
      is needed to determine the impact of the USPSTF change on women's screening
      behaviors and on breast cancer outcomes.

PMID- 24330528
TI  - Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several
      genes of the innate immunity and chemokine-dependent migration pathways.
AB  - BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic
      in Latin America. Thirty percent of infected individuals develop chronic Chagas
      cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the
      most important clinical consequence of T. cruzi infection. The others remain
      asymptomatic (ASY). A possible genetic component to disease progression was
      suggested by familial aggregation of cases and the association of markers of
      innate and adaptive immunity genes with CCC development. Migration of Th1-type T
      cells play a major role in myocardial damage. METHODS: Our genetic analysis
      focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach,
      defined to catch all the genetic information from each gene. The study was
      conducted on a large Brazilian population including 315 CCC cases and 118 ASY
      subjects. RESULTS: The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to
      an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to
      protection to CCC. These associations were confirmed when we restricted the
      analysis to severe CCC, characterized by a left ventricular ejection fraction
      under 40%. CONCLUSIONS: Our data show that polymorphisms affecting key molecules
      involved in several immune parameters (innate immunity signal transduction and T
      cell/monocyte migration) play a role in genetic susceptibility to CCC
      development. This also points out to the multigenic character of CCC, each
      polymorphism imparting a small contribution. The identification of genetic
      markers for CCC will provide information for pathogenesis as well as therapeutic
      targets.

PMID- 24330530
TI  - Scleral buckle infections: microbiological spectrum and antimicrobial
      susceptibility.
AB  - BACKGROUND: The purpose of the present study was to evaluate the microbiological
      spectrum and antimicrobial susceptibility in patients with scleral buckle
      infection. Medical records of all the patients diagnosed as buckle infection at
      L. V. Prasad Eye Institute between July 1992 and June 2012 were reviewed in this
      non-comparative, consecutive, retrospective case series. FINDINGS: A total of 132
      eyes of 132 patients underwent buckle explantation for buckle infection during
      the study period. The incidence of buckle infection at our institute during the
      study period was 0.2% (31 out of 15,022). A total of 124 isolates were identified
      from 102 positive cultures. The most common etiological agent isolated was
      Staphylococcus epidermidis (27/124, 21.77%) followed by Mycobacterium sp.
      (20/124, 16.13%) and Corynebacterium sp. (13/124, 10.48%). The most common gram
      negative bacilli identified was Pseudomonas aeruginosa (9/124, 7.26%). The median
      interval between scleral buckling surgery and onset of symptoms of local
      infection was 30 days. All eyes underwent buckle explantation and median time
      interval between primary SB surgery and explantation was 13 months. Recurrent
      retinal detachment was observed in two cases at 7 and 48 months, respectively,
      after buckle explantation. Gram positive, gram negative, and acid-fast organisms
      isolated from 2003 to 2012 were most commonly susceptible to vancomycin (100%),
      ciprofloxacin (100%), and amikacin (89%). Susceptibility to ciprofloxacin during
      the same time period was observed in 75% (15/20), 100% (13/13), and 87% (7/8) of
      gram positive, gram negative, and acid-fast isolates, respectively. CONCLUSION:
      Scleral buckle infection is relatively rare and has a delayed clinical
      presentation. It is most commonly caused by gram positive cocci. Based on the
      current antimicrobial susceptibility, ciprofloxacin can be used as empirical
      therapy in the management of scleral buckle infections.

PMID- 24330531
TI  - Conventional digital cameras as a tool for assessing leaf area index and biomass
      for cereal breeding.
AB  - Affordable and easy-to-use methods for assessing biomass and leaf area index
      (LAI) would be of interest in most breeding programs. Here, we describe the
      evaluation of a protocol for photographic sampling and image analysis aimed at
      providing low-labor yet robust indicators of biomass and LAI. In this trial, two
      genotypes of triticale, two of bread wheat, and four of tritordeum were studied.
      At six dates during the growing cycle, biomass and LAI were measured
      destructively, and digital photography was taken on the same dates. Several
      vegetation indices were calculated from each image. The results showed that
      repeatable and consistent values of the indices were obtained in consecutive
      photographic samplings on the same plots. The photographic indices were highly
      correlated with the destructive measurements, though the magnitude of the
      correlation was lower after anthesis. This work shows that photographic
      assessment of biomass and LAI can be fast, affordable, have good repeatability,
      and can be used under bright and overcast skies. A practical vegetation index
      derived from pictures is the fraction of green pixels over the total pixels of
      the image, and as it shows good correlations with all biomass variables, is the
      most robust to lighting conditions and has easy interpretation. 

PMID- 24330532
TI  - Validation of the German version of the Nurse-Work Instability Scale: baseline
      survey findings of a prospective study of a cohort of geriatric care workers.
AB  - BACKGROUND: A prospective study of a cohort of nursing staff from nursing homes
      was undertaken to validate the Nurse-Work Instability Scale (Nurse-WIS). Baseline
      investigation data was used to test reliability, construct validity and criterion
      validity. METHOD: A survey of nursing staff from nursing homes was conducted
      using a questionnaire containing the Nurse-WIS along with other survey
      instruments (including SF-12, WAI, SPE). The self-reported number of days' sick
      leave taken and if a pension for reduced work capacity was drawn were recorded.
      The reliability of the scale was checked by item difficulty (P), item
      discrimination (rjt) and by internal consistency according to Cronbach's
      coefficient. The hypotheses for checking construct validity were tested on the
      basis of correlations. Pearson's chi-square was used to test concurrent criterion
      validity; discriminant validity was tested by means of binary logistic
      regression. RESULTS: 396 persons answered the questionnaire (21.3% response
      rate). More than 80% were female and mostly work full-time in a rotating shift
      pattern. Following the test for item discrimination, two items were removed from
      the Nurse-WIS test. According to Cronbach's (0.927) the scale provides a high
      degree of measuring accuracy. All hypotheses and assumptions used to test
      validity were confirmed: As the Nurse-WIS risk increases, health-related quality
      of life, work ability and job satisfaction decline. Depressive symptoms and a
      poor subjective prognosis of earning capacity are also more frequent.
      Musculoskeletal disorders and impairments of psychological well-being are more
      frequent. Age also influences the Nurse-WIS result. While 12.0% of those below
      the age of 35 had an increased risk, the figure for those aged over 55 was 50%.
      CONCLUSION: This study is the first validation study of the Nurse-WIS to date.
      The Nurse-WIS shows good reliability, good validity and a good level of measuring
      accuracy. It appears to be suitable for recording prevention and rehabilitation
      needs among health care workers. If, in the follow-up, the Nurse-WIS likewise
      proves to be a reliable screening instrument with good predictive validity, it
      could ensure that suitable action is taken at an early stage, thereby helping to
      counteract early retirement and the anticipated shortage of health care workers.

PMID- 24330529
TI  - Serious Non-AIDS events: Immunopathogenesis and interventional strategies.
AB  - Despite the major advances in the management of HIV infection, HIV-infected
      patients still have greater morbidity and mortality than the general population.
      Serious non-AIDS events (SNAEs), including non-AIDS malignancies, cardiovascular
      events, renal and hepatic disease, bone disorders and neurocognitive impairment,
      have become the major causes of morbidity and mortality in the antiretroviral
      therapy (ART) era. SNAEs occur at the rate of 1 to 2 per 100 person-years of
      follow-up. The pathogenesis of SNAEs is multifactorial and includes the direct
      effect of HIV and associated immunodeficiency, underlying co-infections and co
      morbidities, immune activation with associated inflammation and coagulopathy as
      well as ART toxicities. A number of novel strategies such as ART intensification,
      treatment of co-infection, the use of anti-inflammatory drugs and agents that
      reduce microbial translocation are currently being examined for their potential
      effects in reducing immune activation and SNAEs. However, currently, initiation
      of ART before advanced immunodeficiency, smoking cessation, optimisation of
      cardiovascular risk factors and treatment of HCV infection are most strongly
      linked with reduced risk of SNAEs or mortality. Clinicians should therefore focus
      their attention on addressing these issues prior to the availability of further
      data. 

PMID- 24330533
TI  - The prevalence of moderate to severe radiographic sacroiliitis and the
      correlation with health status in elderly Swedish men--the MrOS study.
AB  - BACKGROUND: Ankylosing Spondylitis (AS) is a chronic inflammatory disease with
      onset in young adults, but little is known about the prevalence in older age
      groups. Furthermore, there is very limited information of health status of
      elderly patients with AS. Our objective was to estimate the prevalence of
      moderate to severe radiographic sacroiliitis in elderly men and its impact on
      health. METHODS: A cross-sectional, population-based survey, that included 1005
      men aged 69-81 years old, with the primary aim to study risk factors for
      osteoporosis (MrOS), was used. X-rays of the pelvis and spine were done for the
      whole population and then examined by two readers. The prevalences of grade 3-4
      sacroiliitis, syndesmophytes and spondylophytes were ascertained. Using a self
      administered questionnaire, information was obtained on physical activity (PASE),
      functional status (IADL items), health related quality of life - QoL (SF-12) and
      back pain (pain question, Quebec Pain Disability Scale items). RESULTS: Fourteen
      cases with grade 3-4 sacroiliitis were identified, corresponding to a prevalence
      of 1.4% (95%CI: 0.7-2.4). Eight of the patients with sacroiliitis had both AS
      typical and degenerative changes in the spine, 4 had only degenerative changes
      and 2 had only AS-related changes. There were no statistically significant
      differences between those with and without radiographic sacroiliitis regarding
      demographics, anthropometric measures, smoking status or health status, reflected
      by measures on physical activity, functional status, health related QoL and back
      pain. CONCLUSIONS: The prevalence of moderate to severe radiographic sacroiliitis
      was estimated to be 1.4% among elderly men in Sweden. Self-reported health was
      only slightly different in those with sacroiliitis, suggesting that the relative
      impact of AS is modest in this age group.

PMID- 24330534
TI  - The role of diffusion tensor imaging in detecting microstructural changes in
      prodromal Alzheimer's disease.
AB  - The MRI technique diffusion tensor imaging (DTI) is reviewed along with
      microstructural changes associated with prodromal Alzheimer's disease (AD) as a
      potential biomarker for clinical applications. The prodromal stage of AD is
      characterized by mild cognitive impairment (MCI), representing a transitional
      state between normal aging and AD. Microstructural abnormalities on DTI are
      promising in vivo biomarkers of gray and white matter changes associated with the
      progression of AD pathology. Elevated mean diffusivity and decreased fractional
      anisotropy are consistently found in prodromal AD, and even in cognitively normal
      elderly who progress to MCI. However, quality of parameter maps may be affected
      by artifacts of motion, susceptibility, and eddy current-induced distortions. The
      DTI maps are typically analyzed by region-of-interest or voxel-based analytic
      techniques such as tract-based spatial statistics. DTI-based index of diffusivity
      is complementary to macrostructural gray matter changes in the hippocampus in
      detecting prodromal AD. Breakdown of structural connectivity measured with DTI
      may impact cognitive performance during early AD. Furthermore, assessment of
      hippocampal connections may help in understanding the cerebral organization and
      remodeling associated with treatment response. 

PMID- 24330536
TI  - Toxoplasma gondii prevalence in food animals and rodents in different regions of
      China: isolation, genotyping and mouse pathogenicity.
AB  - BACKGROUND: Recent studies of Toxoplasma gondii isolates from animals in
      different regions of China have shown a limited genetic diversity and type China
      1 was the dominant genotype of T. gondii prevalent in Chinese animals. However,
      little has been known concerning the isolation and genotyping of T. gondii
      circulating in chickens, pigs and rodents in China. The aim of the study was to
      characterize samples of T. gondii isolates obtained from naturally infected cats,
      pigs and free-range chickens slaughtered for human consumption in China. METHODS:
      In the present study, brain tissues of 77 animals collected from different areas
      of China, including 24 free-range chickens (Gallus domesticus) , 13 voles (Rattus
      flavipectus), 23 pigs and 17 cats, were bioassayed in mice and viable T. gondii
      were isolated from the brains of eleven. These eleven T. gondii isolates were
      maintained in Kunming (KM) outbred mice and DNA isolated from tissues of infected
      mice was characterized using 11 PCR-restriction fragment length polymorphism (PCR
      RFLP) markers: SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico, and
      CS3. Moreover, to determine mouse virulence of China 1 lineage of parasites, a
      TgCtgy5 genotype isolate was selected randomly and assessed in KM mice with
      different inoculation doses. RESULTS: Results of genotyping revealed that ten
      isolates were type China 1 (ToxoDB PCR-RFLP genotype #9), and TgCksz1 was a new
      genotype that was reported for the first time designated here as ToxoDB PCR-RFLP
      #225. No clonal types I, II and III lineages were found. DNA sequencing of four
      introns (EF1, HP2, UPRT1 and UPRT7) and two genes (GRA6 and GRA7) from
      representative isolates confirmed the results of PCR-RFLP genotyping. The TgCtgy5
      isolate was highly virulent in KM mice; all infected mice died of acute
      toxoplasmosis, irrespective of the inoculation dose. The results indicate that
      mouse virulent isolates of T. gondii are predominantly circulating in cats in
      China. CONCLUSIONS: T. gondii isolated from chickens, pigs, cats and rodents in
      different locations in China were genotyped and the results reconfirmed the
      limited diversity of T. gondii in China and showed that type China 1 lineage was
      dominant in this country.

PMID- 24330537
TI  - Women and HIV in Sub-Saharan Africa.
AB  - Thirty years since the discovery of HIV, the HIV pandemic in sub-Saharan Africa
      accounts for more than two thirds of the world's HIV infections. Southern Africa
      remains the region most severely affected by the epidemic. Women continue to bear
      the brunt of the epidemic with young women infected almost ten years earlier
      compared to their male counterparts. Epidemiological evidence suggests
      unacceptably high HIV prevalence and incidence rates among women. A multitude of
      factors increase women's vulnerability to HIV acquisition, including, biological,
      behavioral, socioeconomic, cultural and structural risks. There is no magic
      bullet and behavior alone is unlikely to change the course of the epidemic.
      Considerable progress has been made in biomedical, behavioral and structural
      strategies for HIV prevention with attendant challenges of developing appropriate
      HIV prevention packages which take into consideration the socioeconomic and
      cultural context of women in society at large. 

PMID- 24330538
TI  - A social network analysis on clinical education of diabetic foot.
AB  - INTRODUCTION: Identification of Educational Influentials (EIs) in clinical
      settings helps considerably to knowledge transfer among health and medical
      practice providers. The aim of this study was identifying EIs in diabetic foot
      ulcers (DFU) by medical students (clerks, interns and residents) and providing
      their relational pattern in this subject. METHODS: Subjects were medical students
      at clerk, intern and resident levels in a local educational hospital. A standard
      questionnaire with four domains (knowledge, communication, participation and
      professional ethics) was used for identifying EIs. Students introduced those
      people with these characteristics who referred them for DFU. Respective
      communication networks were drawn as intra-group (such as resident-resident) and
      inter-group (such as intern-resident) networks and quantitative criteria of
      density, in-degree and out-degree centrality and reciprocity were measured.
      RESULTS: The network density of clerks-residents (0.024) and interns-residents
      (0.038) were higher than clerks-attends (0.015) and interns-attends (0.05);
      indicating that there were more consulting interactions in former networks than
      the latter. Degree centrality in residents-related networks (clerks-residents =
      2.3; interns-residents = 2.6) were higher than attends-related ones (clerks
      attends = 1.1; interns-attends = 1.7), while they were not statistically
      significant. However, In-degree centralization, which indicating a degree of
      variance of the whole network of ingoing relationships, in attends-related
      networks was greater than resident-related networks. CONCLUSION: Resident were
      consulted with almost as same as attends on DFU. It showed that residents were
      playing a remarkable role in knowledge transfer and they can be considered as EIs
      in this clinical setting. It seemed that the availability was the main reason for
      this key role.

PMID- 24330539
TI  - Prophylaxis of neutropenic fever with ciprofloxacin in patients with acute
      myeloid leukemia treated with intensive chemotherapy.
AB  - AIMS: Neutropenic fever is one of the most serious complications after induction
      chemotherapy in acute myeloid leukemia (AML). Prophylaxis with antibiotics for
      prevention of neutropenic fever in AML is controversial and there are few studies
      on this issue from developing countries. METHODS: In this retrospective study, we
      analyzed the clinical data and outcome of patients with AML who did or did not
      receive prophylactic ciprofloxacin 500 mg BD for neutropenic fever. RESULTS: A
      total of 69 AML patients were treated by "3 + 7" protocol for their first
      induction chemotherapy. Prophylaxis was given to 25 of them. Incidence of
      neutropenic fever was the same in both groups (80% vs 82%). Duration of fever and
      the mortality rate were also similar in both groups. CONCLUSION: It seems that in
      developing countries, using prophylactic ciprofloxacin has no significant effect
      on the incidence of neutropenic fever and the outcome of the AML patients.

PMID- 24330540
TI  - Association between polymorphisms in ERCC2 gene and oral cancer risk: evidence
      from a meta-analysis.
AB  - BACKGROUND: Excision repair cross-complementing group 2 (ERCC2) plays important
      roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms
      (SNPs) of ERCC2 gene are suspected to influence the risks of oral cancer. We
      performed a meta-analysis to systematically summarize the possible association of
      ERCC2 rs1799793 and rs13181 polymorphisms with oral cancer risks. METHODS: We
      retrieved the relevant articles from PubMed and Embase databases. Studies were
      selected using specific criteria. ORs and 95% CIs were calculated to assess the
      association. All analyses were performed using the Stata software. RESULTS: Six
      studies were included in this meta-analysis. There were no significant
      associations between ERCC2 rs1799793 and rs13181 polymorphism with overall oral
      cancer risk. In the stratified analysis by ethnicity, no significant associations
      were found. In the stratified analysis by tumor type, the risk of oral
      leukoplakia was significant associated with rs13181 polymorphism (AC vs. AA: OR =
      1.28, 95% CI = 1.01-1.62, P = 0.546 for heterogeneity, I2 = 0.0%; CC vs. AA: OR =
      1.94, 95% CI = 0.99-3.79, P = 0.057 for heterogeneity, I2 = 60.1%; dominant model
      AC + CC vs. AA: OR = 1.35, 95% CI = 1.08-1.69, P = 0.303 for heterogeneity, I2 =
      17.6%; allele C vs. A: OR = 1.38, 95% CI = 1.04-1.82. P = 0.043 for
      heterogeneity, I2 = 56.4%). CONCLUSION: Rs13181 in ERCC2 gene might be associated
      with oral leukoplakia risk.

PMID- 24330541
TI  - On and off-target effects of telomere uncapping G-quadruplex selective ligands
      based on pentacyclic acridinium salts.
AB  - Quadruplexes DNA are present in telomeric DNA as well as in several cancer
      related gene promoters and hence affect gene expression and subsequent biological
      processes. The conformations of G4 provide selective recognition sites for small
      molecules and thus these structures have become important drug-design targets for
      cancer treatment. The DNA G-quadruplex binding pentacyclic acridinium salt RHPS4
      (1) has many pharmacological attributes of an ideal telomere-targeting agent but
      has undesirable off-target liabilities. Notably a cardiovascular effect was
      evident in a guinea pig model, manifested by a marked and sustained increase in
      QTcB interval. In accordance with this, significant interaction with the human
      recombinant beta2 adrenergic receptor, and M1, M2 and M3 muscarinic receptors was
      observed, together with a high inhibition of the hERG tail current tested in a
      patch clamp assay. Two related pentacyclic structures, the acetylamines (2) and
      (3), both show a modest interaction with beta2 adrenergic receptor, and do not
      significatively inhibit the hERG tail current while demonstrating potent telomere
      on-target properties comparing closely with 1. Of the two isomers, the 2-acetyl
      aminopentacycle (2) more closely mimics the overall biological profile of 1 and
      this information will be used to guide further synthetic efforts to identify
      novel variants of this chemotype, to maximize on-target and minimize off-target
      activities. Consequently, the improvement of toxicological profile of these
      compounds could therefore lead to the obtainment of suitable molecules for
      clinical development offering new pharmacological strategies in cancer treatment.

PMID- 24330542
TI  - Mastoidectomy and mastoid obliteration with autologous bone graft: a quality of
      life study.
AB  - BACKGROUND: A mastoid cavity resulting from a canal wall down mastoidectomy can
      result in major morbidity for patients due to chronic otorrhea and infection,
      difficulty with hearing aids and vertigo with temperature changes. Mastoid
      obliteration with reconstruction of the bony external ear canal recreates the
      normal anatomy to avoid such morbidity. Few have the studied the quality of life
      benefit that this procedure confers. METHODS: This retrospective observational
      study was conducted to determine if mastoid obliteration with autologous cranial
      bone graft following mastoidectomy improves quality of life (QOL). Patients with
      cholesteatoma who had mastoidectomy with primary or secondary mastoid
      obliteration by a tertiary otologist were surveyed using the validated Glasgow
      Benefit Inventory (GBI), our primary outcome measure. RESULTS: Fifty-eight
      patients were interviewed. Forty-six were primary obliteration after canal wall
      down mastoidectomy of a primary cholesteatoma. Twelve were secondary obliteration
      of an existing canal wall down mastoid cavity. Overall GBI scores were improved,
      with average scores of 22. Average general subscale scores were 23, physical
      health scores were 25, and social health scores were 22. The primary obliteration
      group had average scores of 19, general subscale scores of 20, physical health
      scores of 21, and social health scores of 22. Those with secondary obliteration
      scored higher, with average scores of 31, general subscale scores of 34, physical
      health scores of 39, and social health scores of 25. CONCLUSION: This study shows
      that mastoidectomy with obliteration using autologous cranial bone graft offers a
      significant QOL benefit. The GBI scores compare favourably with other
      otorhinolaryngology procedures. Secondary obliterations after revision
      mastoidectomy scored much higher than primary obliterations. This is currently
      the only QOL study comparing these two patient groups.

PMID- 24330543
TI  - The social gradient in work and health: a cross-sectional study exploring the
      relationship between working conditions and health inequalities.
AB  - BACKGROUND: Social inequalities in health are widely examined. But the reasons
      behind this phenomenon still remain unclear in parts. It is undisputed that the
      work environment plays a crucial role in this regard. However, the contribution
      of psychosocial factors at work is unclear and inconsistent, and most studies are
      limited with regard to work factors and health outcomes. This study, therefore,
      aimed to explore the role and contribution of various physical and psychosocial
      working conditions to explaining social inequalities in different self-reported
      health outcomes. METHODS: Data from a postal survey among the workforces of four
      medium-sized and large companies from diverse industries of the secondary sector
      in Switzerland were used and analysed. The study sample covered 1,846 employees
      aged 20 and 64 and included significant proportions of unskilled manual workers
      and highly qualified non-manual workers. Cross tabulations and logistic
      regression analyses were performed to study multiple associations between social
      status, work factors and health outcomes. Combinations of educational level and
      occupational position wee used as a measure of social status or class. RESULTS:
      Clear social gradients were observed for almost all adverse working conditions
      and poor health outcomes studied, but in different directions. While physical
      workloads and other typical blue-collar job characteristics not suprisingly, were
      found to be much more common among the lower classes, most psychosocial work
      demands and job resources were more prevalent in the higher classes. Furthermore,
      workers in lower classes, i.e. with lower educational and occupational status,
      were more likely to report poor self-rated health, limited physical functioning
      and long sickness absence, but at the same time were less likely to experience
      increased stress feelings and burnout symptoms showing a reversed health
      gradient. Finally, blue-collar job characteristics contributed substantially to
      the social gradient found in general and physical health outcomes. In contrast,
      white-collar job characteristics made no contribution to explaining the gradient
      in these health outcomes, but instead largely explained the reversed social
      gradient observed for the mental health outcomes. CONCLUSION: The findings
      suggest a more differentiated pattern of the commonly found social gradient in
      health and the differential role of work in this respect.

PMID- 24330544
TI  - Functional outcomes of general medical patients with severe sepsis.
AB  - BACKGROUND: Severe sepsis is a common cause for admission to the general medical
      ward. Previous work has demonstrated substantial new long-term disability in
      patients with severe sepsis, but the short-term functional outcomes of patients
      admitted to the general medical floor -- where the majority of severe sepsis is
      treated -- are largely unknown. METHODS: A retrospective cohort study was
      performed of patients initially admitted to non-ICU medical wards at a tertiary
      care academic medical center. Severe sepsis was confirmed by three physician
      reviewers, using the International Consensus Conference definition of sepsis.
      Baseline functional status, disposition location, and receipt of post-acute
      skilled care were recorded using a structured abstraction instrument. RESULTS:
      3,146 discharges had severe sepsis by coding algorithm; from a random sample of
      111 patients, 64 had the diagnosis of severe sepsis confirmed by reviewers. The
      mean age of the 64 patients was 63.5 years +/- 18.0. Prior to admission, 80% of
      patients lived at home and 50.8% of patients were functionally independent.
      Inpatient mortality was 12.5% and 37.5% of patients were discharged to a nursing
      facility. Of all patients in the cohort, 50.0% were discharged home, and 66.7% of
      patients who were functionally independent at baseline were discharged to home.
      CONCLUSIONS: New physical debility is a common feature of severe sepsis in
      patients initially cared for on the general medical floor. Debility occurs even
      in those with good baseline physical function. Interventions to improve the poor
      functional outcomes of this population are urgently needed.

PMID- 24330546
TI  - Facile one-pot synthesis of polytypic CuGaS2 nanoplates.
AB  - CuGaS2 (CGS) nanoplates were successfully synthesized by one-pot thermolysis of a
      mixture solution of CuCl, GaCl3, and 1-dodecanethiol in noncoordinating solvent 1
      octadecene. Their morphology, crystalline phase, and composition were
      characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), high-resolution transmission electron microscopy (HRTEM),
      powder X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS),
      respectively. Crystalline structure analysis showed that the as-prepared CGS
      nanoplates were polytypic, in which the wurtzite phase was interfaced with
      zincblende domains. The growth process of CGS nanoplates was investigated. It was
      found that copper sulfide nanoplates were firstly formed and then the as-formed
      copper sulfide nanoplates gradually transformed to CGS nanoplates with proceeding
      of the reaction. The optical absorption of the as-synthesized CGS nanoplates was
      also measured and the direct optical bandgap was determined to be 2.24 eV. 

PMID- 24330545
TI  - BSTA: a targeted approach combines bulked segregant analysis with next-
      generation sequencing and de novo transcriptome assembly for SNP discovery in
      sunflower.
AB  - BACKGROUND: Sunflower belongs to the largest plant family on earth, the
      genomically poorly explored Compositae. Downy mildew Plasmopara halstedii
      (Farlow) Berlese & de Toni is one of the major diseases of cultivated sunflower
      (Helianthus annuus L.). In the search for new sources of downy mildew resistance,
      the locus Pl(ARG)on linkage group 1 (LG1) originating from H. argophyllus is
      promising since it confers resistance against all known races of the pathogen.
      However, the mapping resolution in the Pl(ARG) region is hampered by
      significantly suppressed recombination and by limited availability of polymorphic
      markers. Here we examined a strategy developed for the enrichment of molecular
      markers linked to this specific genomic region. We combined bulked segregant
      analysis (BSA) with next-generation sequencing (NGS) and de novo assembly of the
      sunflower transcriptome for single nucleotide polymorphism (SNP) discovery in a
      sequence resource combining reads originating from two sunflower species, H.
      annuus and H. argophyllus. RESULTS: A computational pipeline developed for SNP
      calling and pattern detection identified 219 candidate genes. For a proof of
      concept, 42 resistance gene-like sequences were subjected to experimental SNP
      validation. Using a high-resolution mapping population, 12 SNP markers were
      mapped to LG1. We successfully verified candidate sequences either co-segregating
      with or closely flanking Pl(ARG). CONCLUSIONS: This study is the first successful
      example to improve bulked segregant analysis with de novo transcriptome assembly
      using next generation sequencing. The BSTA pipeline we developed provides a
      useful guide for similar studies in other non-model organisms. Our results
      demonstrate this method is an efficient way to enrich molecular markers and to
      identify candidate genes in a specific mapping interval.

PMID- 24330547
TI  - Synergy of antibacterial and antioxidant activities from crude extracts and
      peptides of selected plant mixture.
AB  - BACKGROUND: A plant mixture containing indigenous Australian plants was examined
      for synergistic antimicrobial activity using selected test microorganisms. This
      study aims to investigate antibacterial activities, antioxidant potential and the
      content of phenolic compounds in aqueous, ethanolic and peptide extracts of plant
      mixture. METHODS: Well diffusion, minimum inhibitory concentration (MIC) and
      minimum bactericidal concentration (MBC) assays were used to test antibacterial
      activity against four pathogenic bacteria namely Staphylococcus aureus,
      Escherichia coli, Bacillus cereus, and Pseudomonas aeruginosa. DPPH (2, 2
      diphenyl-1- picrylhydrazyl) and superoxide dismutase (SOD) assays were used to
      evaluate antioxidant activity. HPLC and gel filtration were used for purification
      of the peptides. Scanning electron microscope was applied to investigate the mode
      of attachment of the peptides on target microbial membranes. RESULTS: Aqueous
      extraction of the mixture showed no inhibition zones against all the test
      bacteria. Mean diameter of inhibition zones for ethanol extraction of this
      mixture attained 8.33 mm, 7.33 mm, and 6.33 mm against S. aureus at corresponding
      concentrations of 500, 250 and 125 mg/ml while E .coli showed inhibition zones of
      9.33 mm, 8.00 mm and 6.66 mm at the same concentrations. B. cereus exhibited
      inhibition zones of 11.33 mm, 10.33 mm and 10.00 mm at concentrations of 500, 250
      and 125 mg/ml respectively. The peptide extract demonstrated antibacterial
      activity against S. aureus, E. coli and B. cereus. The MIC and MBC values for
      ethanol extracts were determined at 125 mg/ml concentration against S. aureus and
      E. coli and B. cereus value was 31.5 mg/ml. MIC and MBC values showed that the
      peptide extract was significantly effective at low concentration of the
      Australian plant mixture (APM). Phenolic compounds were detected in hot aqueous
      and ethanolic extracts of the plant mixture. Hot aqueous, ethanol and peptides
      extracts also exhibited antioxidant activities. CONCLUSIONS: It was concluded
      that APM possessed good antibacterial and antioxidant activities following
      extraction with different solvents. The results suggest that APM provide a new
      source with antibacterial agents and antioxidant activity for nutraceutical or
      medical applications.

PMID- 24330548
TI  - Work-related complaints and diseases of physical therapists - protocol for the
      establishment of a "Physical Therapist Cohort" (PTC) in Germany.
AB  - BACKGROUND: Only few studies deal with the workload of physical therapists and
      the health consequences, although this occupational group is quite important for
      the health care system in many industrialized countries (e.g. ca. 136 000 people
      are currently employed as physical therapists in Germany). Therefore, the current
      state of knowledge of work-related diseases and disorders of physical therapists
      is insufficient. The aim of the "Physical Therapist Cohort" (PTC) study is to
      analyze the association between work-related exposures and diseases among
      physical therapists in Germany. This article describes the protocol of the
      baseline assessment of the PTC study. METHODS/DESIGN: A cross-sectional study
      will be conducted as baseline assessment and will include a representative random
      sample of approximately 300 physical therapists employed in Germany (exposure
      group), and a population-based comparison group (n = 300). The comparison group
      will comprise a sample of working aged (18-65 years) inhabitants of a German
      city. Variables of interest will be assessed using a questionnaire manual
      including questions regarding musculoskeletal, dermal, and infectious diseases
      and disorders as well as psychosocial exposures, diseases and disorders. In
      addition to subjective measures, a clinical examination will be used to objectify
      the questionnaire-based results (n = 50). DISCUSSION: The study, which includes
      extensive data collection, provides a unique opportunity to study the prospective
      association of work-related exposures and associated complaints of physical
      therapists. Baseline results will give first clues with regard to whether and how
      prevalent main exposures of physiotherapeutic work and typical work areas of
      physical therapists are associated with the development of work-related diseases.
      Thereby, this baseline assessment provides the basis for further investigations
      to examine causal relationships in accordance with a longitudinal design.

PMID- 24330549
TI  - Likely Introduction Date of Schmallenberg Virus into France According to Monthly
      Serological Surveys in Cattle.
AB  - To estimate the date of introduction of Schmallenberg virus (SBV) into France,
      the prevalence of antibodies against the virus was determined monthly in cattle
      from two northern departments from August 2011 to April 2012. Seropositive cattle
      were detected from October 2011 in both departments with a prevalence of 55.6% in
      the westernmost department (Meurthe-et-Moselle) and of 12.7% in the easternmost
      department (Manche). Schmallenberg virus seroprevalence then increased rapidly to
      high levels.

PMID- 24330550
TI  - Status of organophosphate and carbamate resistance in Anopheles gambiae sensu
      lato from the south and north Benin, West Africa.
AB  - BACKGROUND: With the rapid spread of pyrethroid resistance in the main malaria
      vectors from Benin and the various resistance mechanisms involved (metabolic
      resistance and knock-down resistance (kdr), it is important to foresee effective
      resistance management strategies. Thus, the knowledge of the insensitive
      acetylcholinesterase (ace-1R) effects on phenotypes of An. gambiae will help us
      to strengthen basic and operational research on the development of strategies
      that will use organophosphates or carbamates as alternatives against pyrethroids
      resistant malaria vectors in the field. METHODS: Larvae and pupae of Anopheles
      gambiae s.l. mosquitoes were collected from the breeding sites in Oueme ,
      Atacora, and Alibori departments. CDC susceptibility tests were conducted on
      unfed female mosquitoes aged 2-5 days old. CDC bioassays were performed with
      stock solutions of fenitrothion (50 MUg per bottle) and bendiocarb (12.5 MUg per
      bottle). PCR techniques were used to detect species and Ace-1 mutations. RESULTS:
      Anopheles gambiae Seme and Kandi populations were susceptible to fenitrothion
      whereas Anopheles gambiae Tanguieta and Malanville populations were resistant.
      An. gambiae populations from Seme, Kandi and Malanville were fully susceptible to
      bendiocarb whereas those from Tanguieta have developed a strong resistance to the
      same insecticide. A slight decrease in mortality rate was observed with 97.91% in
      populations of mosquitoes from Malanville. PCR revealed that all specimens tested
      were Anopheles gambiae s.s.. CONCLUSION: This study demonstrated the need to
      monitor organophosphate (OPs) and Carbamates resistance among populations of the
      An. gambiae s.l. in Benin, to determine its spread and anticipate vector control
      failure where these insecticides are used. However, further studies are needed to
      understand the current distribution of the Ace-1R mutation in other localities in
      the south-north transect Benin.

PMID- 24330551
TI  - Matrix forming characteristics of inner and outer human meniscus cells on 3D
      collagen scaffolds under normal and low oxygen tensions.
AB  - BACKGROUND: Limited intrinsic healing potential of the meniscus and a strong
      correlation between meniscal injury and osteoarthritis have prompted
      investigation of surgical repair options, including the implantation of
      functional bioengineered constructs. Cell-based constructs appear promising,
      however the generation of meniscal constructs is complicated by the presence of
      diverse cell populations within this heterogeneous tissue and gaps in the
      information concerning their response to manipulation of oxygen tension during
      cell culture. METHODS: Four human lateral menisci were harvested from patients
      undergoing total knee replacement. Inner and outer meniscal fibrochondrocytes
      (MFCs) were expanded to passage 3 in growth medium supplemented with basic
      fibroblast growth factor (FGF-2), then embedded in porous collagen type I
      scaffolds and chondrogenically stimulated with transforming growth factor beta3
      (TGF-beta3) under 21% (normal or normoxic) or 3% (hypoxic) oxygen tension for 21
      days. Following scaffold culture, constructs were analyzed biochemically for
      glycosaminoglycan production, histologically for deposition of extracellular
      matrix (ECM), as well as at the molecular level for expression of characteristic
      mRNA transcripts. RESULTS: Constructs cultured under normal oxygen tension
      expressed higher levels of collagen type II (p = 0.05), aggrecan (p < 0.05) and
      cartilage oligomeric matrix protein, (COMP) (p < 0.05) compared to hypoxic
      expanded and cultured constructs. Accumulation of ECM rich in collagen type II
      and sulfated proteoglycan was evident in normoxic cultured scaffolds compared to
      those under low oxygen tension. There was no significant difference in expression
      of these genes between scaffolds seeded with MFCs isolated from inner or outer
      regions of the tissue following 21 days chondrogenic stimulation (p > 0.05).
      CONCLUSIONS: Cells isolated from inner and outer regions of the human meniscus
      demonstrated equivalent differentiation potential toward chondrogenic phenotype
      and ECM production. Oxygen tension played a key role in modulating the
      redifferentiation of meniscal fibrochondrocytes on a 3D collagen scaffold in
      vitro.

PMID- 24330552
TI  - Endometriosis fertility index score maybe more accurate for predicting the
      outcomes of in vitro fertilisation than r-AFS classification in women with
      endometriosis.
AB  - BACKGROUND: Endometriosis is a common disease. The most widely used staging
      system of endometriosis is the revised American Fertility Society classification
      (r-AFS classification) which has limited predictive ability for pregnancy after
      surgery. The endometriosis fertility index (EFI) is used to predict fecundity
      after endometriosis surgery. This diagnostic accuracy study was designed to
      compare the predictive value of the EFI with that of the r-AFS classification for
      IVF outcomes in patients with endometriosis. METHODS: 199 women with
      endometriosis receiving IVF treatment after surgery were analysis. The EFI score
      and r-AFS classification in their ability to predict these IVF outcomes were
      compared in the same population. ROC curves were used to analyse the predictive
      values of the EFI and r-AFS indices for clinical pregnancy, and their accuracies
      were evaluated by sensitivity, specificity, and the Youden's index. RESULTS: The
      Area Under the Curve (AUC) of the EFI score (AUC = 0.641, Standard Error(SE) =
      0.039, P = 0.001, 95% CI = 0.564-0.717, cut-off score = 6) was significantly
      larger than that of the r-AFS classification (AUC = 0.445, SE = 0.041, P = 0.184,
      and 95% CI = 0.364-0.526). The antral follicle count, oestradiol level on day of
      hCG, number of oocytes retrieved, number of oocytes fertilised, and number of
      cleaved embryos in the greater than or equal to 6 EFI score group was greater
      than that of the lower than or equal to 5 EFI score group, and the dose of
      gonadotropin of the greater than or equal to 6 EFI score group were less than
      that in the lower than or equal to 5 EFI score group. Implantation rate, clinical
      pregnancy rate, and cumulative pregnancy rate in the greater than or equal to 6
      EFI score group were higher than in the lower than or equal to 5 EFI score group.
      CONCLUSIONS: It suggests that the EFI has more predictive power for IVF outcomes
      in endometriosis patients than the r-AFS classification. The clinical pregnancy
      rate was higher in patients with EFI greater than or equal to 6 score than with
      EFI lower than or equal to 5 score.

PMID- 24330553
TI  - Rates and risk factors for drug resistance tuberculosis in Northeastern China.
AB  - BACKGROUND: Drug-resistant tuberculosis (TB) has emerged as a major challenge
      toward TB control and prevention. In Lianyungang city, the extent and trend of
      drug resistant TB is not well known. The objective of the survey was to assess
      drug resistance pattern of MTB and risk factors for drug resistant TB, including
      multidrug resistance tuberculosis (MDR-TB) in this area. METHODS: We performed
      drug susceptibility testing on Mycobacterium tuberculosis (MTB) isolates with
      first- and second-line anti-tuberculosis drugs of 1012 culture positive TB cases
      by using the proportion method, who were consecutively enrolled from January 2011
      to December 2012 in Lianyungang city, China. The patterns of drug resistance in
      MTB were investigated and multiple logistic regression analysis was performed to
      assess the risk factors for drug resistant TB. RESULTS: Among the 1012 strains
      tested, 308 (30.4%) strains were resistant to at least one first-line drug; the
      prevalence of MDR-TB was 88 (8.7%), 5 (0.5%) strains were found to be extensively
      drug-resistant tuberculosis (XDR-TB). Female gender was a risk factor for MDR-TB
      (adjusted odds ratio (aOR) 1.763, 95% CI (1.060-2.934). The aged 28-54 years was
      significantly associated with the risk of MDR-TB with an aOR: 2.224, 95% CI
      (1.158-4.273) when compared with those 65 years or older. Patients with previous
      treatment history had a more than 7-fold increased risk of MDR-TB, compared with
      those never previously treated. CONCLUSIONS: The burden of drug resistant TB
      cases is sizeable, which highlights an urgent need to reinforce control,
      detection and treatment strategies for drug resistant TB.

PMID- 24330554
TI  - The contribution of immobility risk factors to the incidence of venous thrombosis
      in an older population.
AB  - BACKGROUND: Venous thrombosis is common in the older population. Assessment of
      risk factors is necessary to implement preventive measures. OBJECTIVES: We
      studied the associations between immobility-related risk factors and thrombosis,
      specifically, hospitalization, surgery, fractures, plaster cast use, minor
      injuries, and transient immobility at home, in an older population. PATIENTS AND
      METHODS: Analyses were performed in the Age and Thrombosis, Acquired and Genetic
      risk factors in the Elderly (AT-AGE) study, a two-center population-based case
      control study. Consecutive cases aged > 70 years with a first-time thrombosis (n
      = 401) and control subjects > 70 years old without a history of thrombosis (n =
      431) were included. Exclusion criteria were active malignancy and severe
      cognitive disorders. We calculated odds ratios (OR) with 95% confidence intervals
      (95% CI) after adjustment for age, sex, body mass index, study center, and
      population-attributable risks. RESULTS: There was a 15-fold (OR 14.8, 95% CI 4.4
      50.4) increased risk of thrombosis within 2 weeks after hospital discharge.
      Surgery (OR 6.6, 95% CI 3.7-11.6), fractures (OR 12.7, 95% CI 3.7-43.7), plaster
      cast (OR 6.2, 95% CI 2.0-18.9), minor leg injuries (OR 1.9, 95% CI 1.1-3.3), and
      transient immobility at home (OR 5.0, 95% CI 2.3-11.2) were all associated with
      thrombosis risk over 3 months. The population-attributable risks for in-hospital
      immobility was 27%, and for out-of-hospital immobility, 15%. CONCLUSIONS: In
      those > 70 years of age, in-hospital and out-of hospital immobility are strong
      risk factors for thrombosis. Additional studies on preventive measures during
      immobilization in this age group should not focus solely on hospital settings.

PMID- 24330555
TI  - Overview of regular dialysis treatment in Japan (as of 31 December 2011).
AB  - A nationwide statistical survey of 4255 dialysis facilities was conducted at the
      end of 2011. Responses were submitted by 4213 facilities (99.0%). The number of
      new patients started on dialysis was 38,613 in 2011. Although the number of new
      patients decreased in 2009 and 2010, it increased in 2011. The number of patients
      who died each year has been increasing; it was 30,743 in 2011, which exceeded
      30,000 for the first time. The number of patients undergoing dialysis has also
      been increasing every year; it was 304,856 at the end of 2011, which exceeded
      300,000 for the first time. The number of dialysis patients per million at the
      end of 2011 was 2385.4. The crude death rate of dialysis patients in 2011 was
      10.2%, which exceeded 10% for the first time in the last 20 years. The mean age
      of new dialysis patients was 67.84 years and the mean age of the entire dialysis
      patient population was 66.55 years. The most common primary cause of renal
      failure among new dialysis patients was diabetic nephropathy (44.3%). Diabetic
      nephropathy was also the most common primary disease among the entire dialysis
      patient population (36.7%), exceeding chronic glomerulonephritis (34.8%) which
      had been the highest until last year. The survey included questions related to
      the Great East Japan Earthquake, which occurred on 11 March 2011. The results on
      items associated with the Great East Japan Earthquake were reported separately
      from this report. The mean uric acid levels of the male and female patients were
      7.30 and 7.19 mg/dL, respectively. Certain drugs for hyperuricemia were
      prescribed for approximately 17% of patients. From the results of the facility
      survey, the number of patients who underwent peritoneal dialysis (PD) was 9642
      and the number of patients who did not undergo PD despite having a peritoneal
      dialysis catheter was 369. A basic summary of the results on the survey items
      associated with PD is included in this report and the details were reported
      separately.

PMID- 24330557
TI  - Blood monocyte count may be a predictor of vascular access failure in
      hemodialysis patients.
AB  - It has been reported that an increase in the counts of white blood cells (WBC)
      and their subpopulations is an independent predictor of atherosclerotic events
      and mortality. On the other hand, vascular access (VA) stenosis is caused by a
      progressive development of neointimal hyperplasia. We examined the relationship
      between VA failure and counts of peripheral WBC and their subpopulations in
      hemodialysis (HD) patients. The study population consisted of 82 patients
      undergoing regular HD. Twenty-two patients, who were unstable, were excluded from
      the study. After one year, we examined the relationship between VA failure and
      the counts of peripheral WBC and their subpopulations. In the follow-up period,
      21 patients had complicated VA failure. The counts of WBC, neutrophils,
      lymphocytes, eosinophils, and basophils did not show a significant difference,
      but a monocyte count of >= 400/MUL was shown to indicate a high probability of VA
      failure. Logistic regression analysis revealed that monocyte count was an
      independent risk factor of VA failure. The peripheral blood monocyte count may be
      a predictor of VA failure in HD patients.

PMID- 24330556
TI  - Long-term treatment of hyperphosphatemia with bixalomer in Japanese hemodialysis
      patients.
AB  - Bixalomer is a nonabsorbable polymer that binds phosphate in the gastrointestinal
      tract and lowers the serum phosphate level by inhibiting phosphate absorption.
      The safety and efficacy of long-term bixalomer treatment were assessed in
      Japanese hemodialysis patients with hyperphosphatemia. This was a multicenter
      open-label study with a 48-week treatment period. The main efficacy endpoints
      were the serum phosphate level and rate of achieving the target serum phosphate
      range (3.5-6.0 mg/dL). Bixalomer was initiated at a dose of 1.5 g/day, which was
      increased to a maximum of 7.5 g/day depending on the serum phosphate response. Of
      248 subjects who started treatment, 179 completed the study. The mean serum
      phosphate level decreased over time and remained around 5.5 mg/dL from weeks 16
      to 48. The target serum phosphate level was reached in >50% of subjects by week 7
      and was maintained in 65.2% to 75.9% until week 48. The incidence of adverse
      events and adverse drug reactions was 94.4% and 29.4%, respectively. There was a
      potential relationship with the study drug for four serious adverse events
      (ischemic colitis, hemorrhagic intestinal diverticulum, esophageal ulcer, and
      acute cholecystitis), which occurred in one patient each. Constipation was the
      most common adverse drug reaction (21.0%). Most adverse events and adverse drug
      reactions occurred soon after starting administration, and their incidence did
      not increase during long-term treatment. Bixalomer did not reduce the bicarbonate
      level or promote metabolic acidosis. Bixalomer is clinically useful for the long
      term treatment of hyperphosphatemia.

PMID- 24330558
TI  - Pigment epithelium-derived factor as a new predictor of mortality among chronic
      kidney disease patients treated with hemodialysis.
AB  - Pigment epithelium-derived factor (PEDF) plays a protective role against
      atherosclerosis. Although serum PEDF level is increased in patients undergoing
      regular hemodialysis (HD), the pathophysiological role of PEDF in HD patients is
      unknown. We measured serum PEDF levels in 74 HD patients, and the association
      between serum PEDF and adverse events such as all-cause death and cardiovascular
      accident was evaluated prospectively. During the follow up of 45.4 +/- 25.1
      months, 24 patients (32.4%) experienced cardiovascular accident and 18 (24.3%)
      died. Significantly higher incidences of all-cause mortality and cardiovascular
      accident were observed in the lower PEDF group than in the higher PEDF group.
      After adjusting for propensity score calculated from multiple confounding factors
      (age, gender, systolic blood pressure, history of previous cardiovascular
      disease, level of carbonyl content, albumin, hemoglobin, total cholesterol,
      creatinine, C-reactive protein, dialysis vintage, Kt/V-urea and history of
      diabetes), lower predialytic PEDF was a significant risk factor for all-cause
      mortality (relative hazard = 6.060, standard error = 0.68467, P = 0.0085). Lower
      levels of predialytic PEDF was associated with an increased risk of mortality.

PMID- 24330559
TI  - Double-filtration plasmapheresis for the treatment of patients with recalcitrant
      atopic dermatitis.
AB  - The management of recalcitrant atopic dermatitis (AD) is a challenging issue for
      both clinicians and patients. In this study, we evaluate the clinical efficacy
      and safety of double-filtration plasmapheresis (DFPP) in patients with
      recalcitrant AD. Eighteen patients with recalcitrant AD whose clinical condition
      had not been effectively controlled by current standard medical therapies were
      treated by either a single course of DFPP (N = 9) or with standard medical
      therapies only (N = 9). Clinical severity of AD was measured at baseline and at 1
      and 4 weeks after treatment in patients in the DFPP group and at the
      corresponding time points in the control group using the standardized clinical
      severity scoring system for atopic dermatitis (SCORAD). In the nine patients who
      underwent DFPP, SCORAD values significantly decreased from 80.6 +/- 16.7 (mean +/
      SD) at baseline to 65.9 +/- 20.1 at 1 week and 69.8 +/- 20.4 at 4 weeks after
      DFPP treatment (Wilcoxon signed-rank test, P < 0.05). No significant side-effects
      were observed during DFPP treatment. In the nine patients with recalcitrant AD
      who were treated with standard medical therapies, there were no significant
      differences between the SCORAD values at baseline (70.6 +/- 13.9), 1 week (68.0
      +/- 14.4), and 4 weeks (69.8 +/- 17.7) (P > 0.05). DFPP resulted in significant
      clinical improvements in patients with recalcitrant AD. Further studies are
      needed to evaluate the long-term clinical usefulness of DFPP in the treatment of
      patients with recalcitrant AD.

PMID- 24330560
TI  - Catheter-related atrial thrombus in a patient on hemodialysis.

PMID- 24330561
TI  - Two transfusion-related acute lung injury episodes in a recipient of AB plasma
      from multiparous donors.

PMID- 24330562
TI  - Timing of continuous renal replacement therapy initiation in septic shock and
      acute kidney injury.

PMID- 24330563
TI  - Timing for initiation of continuous renal replacement therapy in patients with
      septic shock and acute kidney injury.

PMID- 24330564
TI  - Importance of isolated anti-hbc in detection of occult hepatitis B virus
      infection in hemodialysis patients: reply.

PMID- 24330568
TI  - Age and sharing of needle injection equipment in a cohort of Massachusetts
      injection drug users: an observational study.
AB  - BACKGROUND: Hepatitis C infection (HCV) among individuals aged 15-24 years has
      increased in Massachusetts, likely due to injection drug use. The prevalence of
      injection equipment sharing (sharing) and its association with age was examined
      in a cohort of out-of-treatment Massachusetts substance users. METHODS: This
      analysis included baseline data from a behavioral intervention with substance
      users. Younger and older (<25 versus >= 25 years) injection drug users were
      compared on demographic characteristics, substance use practices, including
      factors present during the most recent sharing event ("event-level factors"), and
      HCV testing history. RESULTS: Sharing was reported by 41% of the 484 individuals
      who reported injection drug use in the past 30 days. Prevalence of sharing varied
      by age (50% <25 years old versus 38% >= 25 years, p=0.02). In a multivariable
      logistic regression model younger versus older individuals had twice the odds of
      sharing (95% CI=1.26, 3.19). During their most recent sharing event, fewer
      younger individuals than older had their own drugs available (50% versus 75%,
      p<0.001); other injection event-level factors did not vary by age. In the
      presence of PTSD, history of exchanging sex for money, or not being US born,
      prevalence of sharing by older users was higher and was similar to that of
      younger users, such that there was no association between age and sharing.
      CONCLUSIONS: In this cohort of injection drug users, younger age was associated
      with higher prevalence of sharing, but only in the absence of certain stressors.
      Harm reduction efforts might benefit from intervening on mental health and other
      stressors in addition to substance use. Study findings suggest a particular need
      to address the dangers of sharing with young individuals initiating injection
      drug use.

PMID- 24330569
TI  - Putting an 'End' to HIV mRNAs: capping and polyadenylation as potential
      therapeutic targets.
AB  - Like most cellular mRNAs, the 5' end of HIV mRNAs is capped and the 3' end
      matured by the process of polyadenylation. There are, however, several rather
      unique and interesting aspects of these post-transcriptional processes on HIV
      transcripts. Capping of the highly structured 5' end of HIV mRNAs is influenced
      by the viral TAT protein and a population of HIV mRNAs contains a trimethyl-G cap
      reminiscent of U snRNAs involved in splicing. HIV polyadenylation involves active
      repression of a promoter-proximal polyadenylation signal, auxiliary upstream
      regulatory elements and moonlighting polyadenylation factors that have additional
      impacts on HIV biology outside of the constraints of classical mRNA 3' end
      formation. This review describes these post-transcriptional novelties of HIV gene
      expression as well as their implications in viral biology and as possible targets
      for therapeutic intervention. 

PMID- 24330570
TI  - Effects of recreational soccer in men with prostate cancer undergoing androgen
      deprivation therapy: study protocol for the 'FC Prostate' randomized controlled
      trial.
AB  - BACKGROUND: Androgen deprivation therapy (ADT) is a cornerstone in the treatment
      of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects
      of ADT are widely reported and investigations into the potential of exercise to
      ameliorate the effects of treatment are warranted. The 'Football Club (FC)
      Prostate' study is a randomized trial comparing the effects of soccer training
      with standard treatment approaches on body composition, cardiovascular function,
      physical function parameters, glucose tolerance, bone health, and patient
      reported outcomes in men undergoing ADT for prostate cancer. METHODS/DESIGN:
      Using a single-center randomized controlled design, 80 men with histologically
      confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6
      months or more at The Copenhagen University Hospital will be enrolled on this
      trial. After baseline assessments eligible participants will be randomly assigned
      to a soccer training group or a control group receiving usual care. The soccer
      intervention will consist of 12 weeks of training 2-3 times/week for 45-60 min
      after which the assessment protocol will be repeated. Soccer training will then
      continue bi-weekly for an additional 20 weeks at the end of which all measures
      will be repeated to allow for additional analyses of long-term effects. The
      primary endpoint is changes in lean body mass from baseline to 12 weeks assessed
      by dual X-ray absorptiometry scan. Secondary endpoints include changes of
      cardiovascular, metabolic, and physical function parameters, as well as markers
      of bone metabolism and patient-reported outcomes. DISCUSSION: The FC Prostate
      trial will assess the safety and efficacy of a novel soccer-training approach to
      cancer rehabilitation on a number of clinically important health outcomes in men
      with advanced prostate cancer during ADT. The results may pave the way for
      innovative, community-based interventions in the approach to treating prostate
      cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01711892.

PMID- 24330571
TI  - T cell immunohistochemistry refines lung transplant acute rejection diagnosis and
      grading.
AB  - OBJECTIVE: Lung transplant volume has been increasing. However, inaccurate and
      uncertain diagnosis for lung transplant rejection hurdles long-term outcome due
      to, in part, interobserver variability in rejection grading. Therefore, a more
      reliable method to facilitate diagnosing and grading rejection is warranted.
      METHOD: Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for
      histological and immunohistochemical assessment. No immunosuppressive treatment
      was administered. We explored the value of interstitial T lymphocytes
      quantification by immunohistochemistry and compared the role of T cell
      immunohistochemistry with H&E staining in diagnosing and grading lung transplant
      rejection. RESULTS: Typical acute rejection from grade A1 to A4 was found.
      Rejection severity was heterogeneously distributed in one-third transplanted
      lungs (14/40): lesions in apex and center were more augmented than in the base
      and periphery of the grafts, respectively. Immunohistochemistry showed profound
      difference in T lymphocyte infiltration among grade A1 to A4 rejections. The
      coincidence rate of H&E and immunohistochemistry was 77.5%. The amount of
      interstitial T lymphocyte infiltration increased gradually with the upgrading of
      rejection. The statistical analysis demonstrated that the difference in the
      amount of interstitial T lymphocytes between grade A2 and A3 was not obvious.
      However, T lymphocytes in lung tissue of grade A4 were significantly more
      abundant than in other grades. CONCLUSIONS: Rejection severity was
      heterogeneously distributed within lung grafts. Immunohistochemistry improves the
      sensitivity and specificity of rejection diagnosis, and interstitial T lymphocyte
      quantitation has potential value in diagnosing and monitoring lung allograft
      rejection. VIRTUAL SLIDES: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1536075282108217.

PMID- 24330572
TI  - Effect of EDTA-anticoagulated whole blood storage on cell morphology examination.
      A need for standardization.

PMID- 24330573
TI  - Sequencing the transcriptome of milk production: milk trumps mammary tissue.
AB  - BACKGROUND: Studies of normal human mammary gland development and function have
      mostly relied on cell culture, limited surgical specimens, and rodent models.
      Although RNA extracted from human milk has been used to assay the mammary
      transcriptome non-invasively, this assay has not been adequately validated in
      primates. Thus, the objectives of the current study were to assess the
      suitability of lactating rhesus macaques as a model for lactating humans and to
      determine whether RNA extracted from milk fractions is representative of RNA
      extracted from mammary tissue for the purpose of studying the transcriptome of
      milk-producing cells. RESULTS: We confirmed that macaque milk contains
      cytoplasmic crescents and that ample high-quality RNA can be obtained for
      sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk
      cell fractions more accurately represented RNA from mammary epithelial cells
      (cells that produce milk) than did RNA from whole mammary tissue. Mammary
      epithelium-specific transcripts were more abundant in macaque milk fat, whereas
      adipose or stroma-specific transcripts were more abundant in mammary tissue.
      Functional analyses confirmed the validity of milk as a source of RNA from milk
      producing mammary epithelial cells. CONCLUSIONS: RNA extracted from the milk fat
      during lactation accurately portrayed the RNA profile of milk-producing mammary
      epithelial cells in a non-human primate. However, this sample type clearly
      requires protocols that minimize RNA degradation. Overall, we validated the use
      of RNA extracted from human and macaque milk and provided evidence to support the
      use of lactating macaques as a model for human lactation.

PMID- 24330574
TI  - Expression profiling in spondyloarthropathy synovial biopsies highlights changes
      in expression of inflammatory genes in conjunction with tissue remodelling genes.
AB  - BACKGROUND: In the spondyloarthropathies, the underlying molecular and cellular
      pathways driving disease are poorly understood. By undertaking a study in knee
      synovial biopsies from spondyloarthropathy (SpA) and ankylosing spondylitis (AS)
      patients we aimed to elucidate dysregulated genes and pathways. METHODS: RNA was
      extracted from six SpA, two AS, three osteoarthritis (OA) and four normal control
      knee synovial biopsies. Whole genome expression profiling was undertaken using
      the Illumina DASL system, which assays 24000 cDNA probes. Differentially
      expressed candidate genes were then validated using quantitative PCR and
      immunohistochemistry. RESULTS: Four hundred and sixteen differentially expressed
      genes were identified that clearly delineated between AS/SpA and control groups.
      Pathway analysis showed altered gene-expression in oxidoreductase activity, B
      cell associated, matrix catabolic, and metabolic pathways. Altered "myogene"
      profiling was also identified. The inflammatory mediator, MMP3, was strongly
      upregulated (5-fold) in AS/SpA samples and the Wnt pathway inhibitors DKK3 (2.7
      fold) and Kremen1 (1.5-fold) were downregulated. CONCLUSIONS: Altered expression
      profiling in SpA and AS samples demonstrates that disease pathogenesis is
      associated with both systemic inflammation as well as local tissue alterations
      that may underlie tissue damaging modelling and remodelling outcomes. This
      supports the hypothesis that initial systemic inflammation in
      spondyloarthropathies transfers to and persists in the local joint environment,
      and might subsequently mediate changes in genes directly involved in the
      destructive tissue remodelling.

PMID- 24330575
TI  - Impact of viral drift on vaccination dynamics and patterns of seasonal influenza.
AB  - BACKGROUND: Much research has been devoted to the determination of optimal
      vaccination strategies for seasonal influenza epidemics. However, less attention
      has been paid to whether this optimization can be achieved within the context of
      viral drift. METHODS: We developed a mathematical model that links different
      intra-seasonal dynamics of vaccination and infection to investigate the effect of
      viral drift on optimal vaccination for minimizing the total number of infections.
      The model was computationally implemented using a seasonal force of infection,
      with estimated parameters from the published literature. RESULTS: Simulation
      results show that the pattern of large seasonal epidemics is strongly correlated
      with the duration of specific cross-protection immunity induced by natural
      infection. Considering a random vaccination, our simulations suggest that the
      effect of vaccination on epidemic patterns is largely influenced by the duration
      of protection induced by strain-specific vaccination. We found that the
      protection efficacy (i.e., reduction of susceptibility to infection) of vaccine
      is a parameter that could influence these patterns, particularly when the
      duration of vaccine-induced cross-protection is lengthened. CONCLUSIONS: Given
      the uncertainty in the timing and nature of antigenically drifted variants, the
      findings highlight the difficulty in determining optimal vaccination dynamics for
      seasonal epidemics. Our study suggests that the short- and long-term impacts of
      vaccination on seasonal epidemics should be evaluated within the context of
      population-pathogen landscape for influenza evolution.

PMID- 24330577
TI  - The association between CYP2C19 genotype and of in-stent restenosis among
      patients with vertebral artery stent treatment.
AB  - AIMS: Preventing stroke through endovascular treatment with vertebral artery
      stent remains a great challenge due to the occurrence of an in-stent restenosis.
      MATERIALS & METHODS: In this study, a retrospective analysis was conducted in 90
      patients who had been treated with VAS between 2004 and 2011 in Nanjing Drum
      Tower Hospital. Patients were followed up at 3 months, 6 months,and 1 year after
      VAS treatment and annually thereafter. For each time point, neurological function
      tests, vessel ultrasound and computer tomography angiography were performed to
      preliminarily screen the vessel stenosis. Digital subtraction angiography was
      used to verify the narrow sign on CTA or ultrasound. Clinical features of each
      patient including clopidogrel metabolization genes (CYP2C19, CYP3A4, and P2Y12)
      were recorded with purpose to investigate the possible risk factors for the
      development of ISR. RESULTS: Single factor analysis dem-onstrated that
      hyperlipidemia (P < 0.05) and CYP2C19 (P < 0.01) loss-of-function geno-type
      increased the likelihood of ISR. A multiple logistic cox regression analysis also
      showed that stroke patients with hyperlipidemia (HR 3.719, 95% CI: 1.094-12.637,
      P = 0.035), and CYP2C19 loss-of-function genotype (HR 2.959, 95% CI: 1.325-6.610,
      P = 0.008) were more likely to suffer from ISR. Furthermore, CYP2C19 alleles were
      mainly divided into three groups: wt/wt (CYP2C19 *1/*1), wt/m (CYP2C19 *1/*2 and
      *1/*3), and m/m (CYP2C19 *2/*2,*2/*3 and*3/*3). Recurrent rate of ischemic stroke
      in m/m and wt/m groups was higher than the wt/wt group (OR: 0.141, 95% CI: 0.016
      1.221, P = 0.042). CONCLUSION: The study leads to the conclusion that
      hyperlipidemia and CYP2C19 impotency are possible risk factors for the
      development of ISR in VAS-treated patients with ischemic. Moreover, VAS-treated
      patients with CYP2C19 impotency were susceptible to recurrent stroke during our
      54-month follow-up.

PMID- 24330576
TI  - Impact of dietary fiber intake on glycemic control, cardiovascular risk factors
      and chronic kidney disease in Japanese patients with type 2 diabetes mellitus:
      the Fukuoka Diabetes Registry.
AB  - BACKGROUND: Dietary fiber is beneficial for the treatment of type 2 diabetes
      mellitus, although it is consumed differently in ethnic foods around the world.
      We investigated the association between dietary fiber intake and obesity,
      glycemic control, cardiovascular risk factors and chronic kidney disease in
      Japanese type 2 diabetic patients. METHODS: A total of 4,399 patients were
      assessed for dietary fiber intake using a brief self-administered diet history
      questionnaire. The associations between dietary fiber intake and various
      cardiovascular risk factors were investigated cross-sectionally. RESULTS: Body
      mass index, fasting plasma glucose, HbA1c, triglyceride and high-sensitivity C
      reactive protein negatively associated with dietary fiber intake after adjusting
      for age, sex, duration of diabetes, current smoking, current drinking, total
      energy intake, fat intake, saturated fatty acid intake, leisure-time physical
      activity and use of oral hypoglycemic agents or insulin. The homeostasis model
      assessment insulin sensitivity and HDL cholesterol positively associated with
      dietary fiber intake. Dietary fiber intake was associated with reduced prevalence
      of abdominal obesity, hypertension and metabolic syndrome after multivariate
      adjustments including obesity. Furthermore, dietary fiber intake was associated
      with lower prevalence of albuminuria, low estimated glomerular filtration rate
      and chronic kidney disease after multivariate adjustments including protein
      intake. Additional adjustments for obesity, hypertension or metabolic syndrome
      did not change these associations. CONCLUSION: We demonstrated that increased
      dietary fiber intake was associated with better glycemic control and more
      favorable cardiovascular disease risk factors including chronic kidney disease in
      Japanese type 2 diabetic patients. Diabetic patients should be encouraged to
      consume more dietary fiber in daily life.

PMID- 24330578
TI  - Differences in timing of mating swarms in sympatric populations of Anopheles
      coluzzii and Anopheles gambiae s.s. (formerly An. gambiae M and S molecular
      forms) in Burkina Faso, West Africa.
AB  - BACKGROUND: The M and S molecular forms of Anopheles gambiae s.s. Giles appear to
      have speciated in West Africa and the M form is now formally named An. coluzzii
      Coetzee & Wilkerson sp.n. and the S form retains the nominotypical name
      (abbreviated here to An. gambiae). Reproductive isolation is thought to be the
      main barrier to hybridisation; even though both species are found in the same
      mating swarms, hybrid fertilisations in copulae have not been found in the study
      area. The aim of the study, therefore, was to determine whether differences in
      circadian and/or environmental control over the timing of swarming in the two
      species contribute to reproductive isolation. METHODS: The timing of male
      swarming in these species was recorded four nights per month over four years at
      five swarming sites in each of two villages. The timing of the start and end of
      swarming, and the concurrent environmental parameters, temperature, humidity and
      light intensity, were recorded for n = 20 swarms/month/species. The timing of
      'spontaneous' activity at dusk of individual An. coluzzii and An. gambiae males
      was video-recorded in an actograph outdoors for 21 nights. RESULTS: Of the
      environmental parameters considered, swarming was most strongly correlated with
      sunset (r2 > 0.946). Anopheles gambiae started and stopped swarming earlier than
      An. coluzzii (3:35 +/- 0:68 min:sec and 4:51 +/- 1:21, respectively), and the
      mean duration of swarming was 23:37 +/- 0:33 for An. gambiae and 21:39 +/- 0:33
      for An. coluzzii. Accordingly, in principle, whenever both species swarm over the
      same marker, a mean of 15.3 +/- 3.1% of An. gambiae swarming would occur before
      An. coluzzii males arrived, and 19.5 +/- 4.55% of An. coluzzii swarming would
      occurred after An. gambiae males had stopped swarming. These results are
      consistent with the finding that An. gambiae males became active in the actograph
      09:35 +/- 00:22 min:sec earlier than An. coluzzii males. CONCLUSIONS: The timing
      of swarming and spontaneous activity at dusk are primarily under circadian
      control, with the phase linked closely to sunset throughout the year. The mating
      activity of these two species is temporally segregated for 15-20% of the swarming
      period, which may contribute to the observed reproductive isolation of these
      species in local sympatric populations.

PMID- 24330579
TI  - An observational study on the expression levels of MDM2 and MDMX proteins, and
      associated effects on P53 in a series of human liposarcomas.
AB  - BACKGROUND: Inactivation of wild type P53 by its main cellular inhibitors (MDM2
      and MDMX) is a well recognised feature of tumour formation in liposarcomas. MDM2
      over-expression has been detected in approximately 80% of liposarcomas but only
      limited information is available about MDMX over-expression. To date, we are not
      aware of any study that has described the patterns of MDM2 and MDMX co-expression
      in liposarcomas. Such information has become more pertinent as various novel MDM2
      and/or MDMX single and dual affinity antagonist compounds are emerging as an
      alternative approach for potential targeted therapeutic strategies. METHODS: We
      analysed a case series of 61 fully characterized liposarcomas of various sub
      types by immunohistochemistry, to assess the expression levels of P53, MDM2 and
      MDMX, simultaneously. P53 sequencing was performed in all cases that expressed
      P53 protein in 10% or more of cells to rule out mutation-related over-expression.
      RESULTS: 50 cases over-expressed MDM2 and 42 of these co-expressed MDMX at
      varying relative levels. The relative expression levels of the two proteins with
      respect to each other were subtype-dependent. This apparently affected the
      detected levels of P53 directly in two distinct patterns. Diminished levels of
      P53 were observed when MDM2 was significantly higher in relation to MDMX,
      suggesting a dominant role for MDM2 in the degradation of P53. Higher levels of
      P53 were noted with increasing MDMX levels suggesting an interaction between MDM2
      and MDMX that resulted in a reduced efficiency of MDM2 in degrading P53. Of the
      26 cases of liposarcoma with elevated P53 expression, 5 were found to have a
      somatic mutation in the P53 gene. CONCLUSIONS: The results suggest that complex
      dynamic interactions between MDM2 and MDMX proteins may directly affect the
      cellular levels of P53. This therefore suggests that careful characterization of
      both these markers will be necessary in tumours when considering in vivo
      evaluation of novel blocker compounds for MDM proteins, as a therapeutic strategy
      to restore wild type P53 function.

PMID- 24330580
TI  - Isolation of heterotrophic diazotrophic bacteria from estuarine surface waters.
AB  - The wide distribution of diverse nitrogenase (nifH) genes affiliated with those
      of heterotrophic bacteria in marine and estuarine waters indicates ubiquity and
      an ecologically relevant role for heterotrophic N2 -fixers (diazotrophs) in
      aquatic nitrogen (N) cycling. However, the lack of cultivated representatives
      currently precludes an evaluation of their N2 -fixing capacity. In this study,
      microoxic or anoxic N-free media were inoculated with estuarine Baltic Sea
      surface water to select for N2 -fixers. After visible growth and isolation of
      single colonies on oxic plates or in anoxic agar tubes, nifH gene amplicons were
      obtained from 64 strains and nitrogenase activity, applying the acetylene
      reduction assay, was confirmed for 40 strains. Two strains, one
      Gammaproteobacterium affiliated with Pseudomonas and one Alphaproteobacterium
      affiliated with Rhodopseudomonas were shown to represent established members of
      the indigenous diazotrophic community in the Baltic Sea, with abundances of up to
      7.9 * 10(4) and 4.7 * 10(4)  nifH copies l(-1) respectively. This study reports
      media for successful isolation of heterotrophic diazotrophs. The applied
      methodology and the obtained strains will facilitate future identification of
      factors controlling heterotrophic diazotrophic activity in aquatic environments,
      which is a prerequisite for understanding and evaluating their ecology and
      contribution to N cycling at local and regional scales.

PMID- 24330581
TI  - Down regulation of SPAG9 reduces growth and invasive potential of triple-negative
      breast cancer cells: possible implications in targeted therapy.
AB  - BACKGROUND: Recently, we reported an association of a novel cancer testis (CT)
      antigen, sperm-associated antigen 9 (SPAG9) expression in breast cancer clinical
      samples, indicating its potential role in carcinogenesis. Around 15% breast
      cancers are designated as triple-negative for which treatment modalities are
      limited. Therefore, in the present study, we assessed the role of SPAG9 in triple
      negative breast cancer cells. METHODS: SPAG9 mRNA and protein expression was
      investigated in various breast cancer cells of different hormone receptor status
      and different subtypes by employing reverse transcriptase-polymerase chain
      reaction (RT-PCR), real time PCR, Western blotting, indirect immunofluorescence
      (IIF) and fluorescence activated cell sorting (FACS). Employing plasmid-based
      small interfering RNA (siRNA) approach, knockdown of SPAG9 was carried out in
      triple-negative breast cancer cells, MDA-MB-231, to assess its role on various
      malignant properties in vitro and in vivo. RESULTS: SPAG9 mRNA and protein
      expression was detected in all breast cancer cells. Further, IIF results showed
      that SPAG9 was predominantly localized in the cytoplasm of breast cancer cells.
      FACS analysis revealed distinct SPAG9 surface localization in breast cancer
      cells. Gene silencing of SPAG9 resulted in significant reduction in cellular
      proliferation, colony forming ability, migration, invasion and cellular motility
      of MDA-MB-231 cells. Further, ablation of SPAG9 expression resulted in reduction
      in the tumor growth of human breast cancer xenograft in nude mice in vivo.
      CONCLUSIONS: In summary, our data indicated that down regulation of SPAG9 reduces
      growth and invasive potential of triple-negative breast cancer cells, suggesting
      that SPAG9 may be a potential target for therapeutic use.

PMID- 24330583
TI  - Annealing temperature effect on self-assembled Au droplets on Si (111).
AB  - We investigate the effect of annealing temperature on self-assembled Au droplets
      on Si (111). The annealing temperature is systematically varied while fixing
      other growth parameters such as deposition amount and annealing duration clearly
      to observe the annealing temperature effect. Self-assembled Au droplets are
      fabricated by annealing from 50 degrees C to 850 degrees C with 2-nm Au
      deposition for 30 s. With increased annealing temperatures, Au droplets show
      gradually increased height and diameter while the density of droplets
      progressively decreases. Self-assembled Au droplets with fine uniformity can be
      fabricated between 550 degrees C and 800 degrees C. While Au droplets become much
      larger with increased deposition amount, the extended annealing duration only
      mildly affects droplet size and density. The results are systematically analyzed
      with cross-sectional line profiles, Fourier filter transform power spectra,
      height histogram, surface area ratio, and size and density plots. This study can
      provide an aid point for the fabrication of nanowires on Si (111). 

PMID- 24330582
TI  - An aryl hydrocarbon receptor induces VEGF expression through ATF4 under glucose
      deprivation in HepG2.
AB  - BACKGROUND: Aryl hydrocarbon receptor (AhR) not only regulates drug-metabolizing
      enzyme expression but also regulates cancer malignancy. The steps to the
      development of malignancy include angiogenesis that is induced by tumor
      microenvironments, hypoxia, and nutrient deprivation. Vascular endothelial growth
      factor (VEGF) plays a central role in the angiogenesis of cancer cells, and it is
      induced by activating transcription factor 4 (ATF4). RESULTS: Recently, we
      identified that glucose deprivation induces AhR translocation into the nucleus
      and increases CYP1A1 and 1A2 expression in HepG2 cells. Here, we report that the
      AhR pathway induces VEGF expression in human hepatoblastoma HepG2 cells under
      glucose deprivation, which involves ATF4. ATF4 knockdown suppressed VEGF
      expression under glucose deprivation. Moreover, AhR knockdown suppressed VEGF and
      ATF4 expression under glucose deprivation at genetic and protein levels.
      CONCLUSIONS: The AhR-VEGF pathway through ATF4 is a novel pathway in glucose
      deprived liver cancer cells that is related to the microenvironment within a
      cancer tissue affecting liver cancer malignancy.

PMID- 24330584
TI  - Follicular expression of follicle stimulating hormone receptor variants in the
      ewe.
AB  - BACKGROUND: Several alternatively-spliced mRNA transcripts of the follicle
      stimulating hormone receptor (FSHR) have been identified in sheep, including FSHR
      1 (G protein-coupled form), FSHR-2 (dominant negative form), and FSHR-3 (growth
      factor type-1 form). Our objective was to determine which of these variants is
      predominantly expressed in follicles collected from ewes at various times after
      estrus. METHODS: Suffolk-cross ewes (n = 8) were allowed to come into estrus
      naturally and were euthanized 24 (n = 3), 36 (n = 3), or 48 (n = 2) hours after
      the onset of estrus. All visible follicles were measured, aspirated and pooled
      according to follicular diameter: small (<= 2.0 mm), medium (2.1-4.0 mm), large
      (4.1-6.0 mm), and preovulatory (> = 6.1 mm). Aspirated cells were separated from
      follicular fluid by centrifugation. Total RNA was extracted from cell pellets and
      reverse transcribed. The resulting cDNA was subjected to qPCR, using primer sets
      designed to amplify each variant specifically. Gene expression was normalized to
      that of beta-actin within samples, and compared by analysis of variance with the
      level of significant differences set at p < .05. RESULTS: Relative expression of
      FSHR-3 exceeded that of both FSHR-1 and FSHR-2 in medium follicles, and tended to
      be higher in small follicles (p = .09) regardless of time after onset of estrus,
      and thus results from different time points were pooled. Expression of FSHR-3 was
      greater than that of FSHR-2 and luteinizing hormone receptor (LHR) in small and
      medium follicles. Expression of LHR was greatest in preovulatory follicles.
      CONCLUSIONS: These experiments show that in addition to the well characterized G
      protein-coupled form of the FSHR, alternatively spliced variants of the FSHR may
      participate in follicular dynamics during follicular waves of the sheep estrous
      cycle. Furthermore, these results indicate that an "alternatively" spliced form
      of the FSHR (FSHR-3) is the predominant form of the FSHR in the sheep.

PMID- 24330585
TI  - Design, synthesis and evaluation of antidepressant activity of novel 2-methoxy 1,
      8 naphthyridine 3-carboxamides as 5-HT3 receptor antagonists.
AB  - A series of novel 1,8-naphthyridine-3-carboxamides as 5-HT3 receptor antagonists
      were synthesized with an intention to explore the antidepressant activity of
      these compounds. The title carboxamides were designed using ligand-based approach
      keeping in consideration the structural requirement of the pharmacophore of 5-HT3
      receptor antagonists. The compounds were synthesized using appropriate synthetic
      route from the starting material nicotinamide. 5-HT3 receptor antagonism of all
      the compounds, which was denoted in the form of pA2 value, was determined in
      longitudinal muscle myenteric plexus preparation from guinea-pig ileum against 5
      HT3 agonist, 2-methyl-5-HT. Compound 8g (2-methoxy-1, 8-naphthyridin-3-yl) (2
      methoxy phenyl piperazine-1-yl) methanone was identified as the most active
      compound, which expressed a pA2 value of 7.67. The antidepressant activity of all
      the compounds was examined in mice model of forced swim test (FST); importantly,
      none of the compounds was found to cause any significant changes in the locomotor
      activity of mice at the tested dose levels. In FST, the compounds with
      considerably higher pA2 value exhibited promising antidepressant-like activity,
      whereas compounds with lower pA2 value did not show antidepressant-like activity
      as compared to the control group. 

PMID- 24330586
TI  - Spoiled breast milk and bad water; local understandings of diarrhea causes and
      prevention in rural Sierra Leone.
AB  - BACKGROUND: Globally, diarrhea remains a leading killer of young children. In
      Sierra Leone, one in seven children die before their fifth birthday and diarrhea
      is a leading cause. Studies that emphasize the demand-side of health
      interventions -- how caregivers understand causation and prevention of diarrhea -
      have been neglected in research and programming. METHODS: We undertook applied
      qualitative research including 68 in-depth interviews and 36 focus group
      discussions with mothers, fathers and older female caretakers to examine the
      causes and prevention of childhood diarrhea in villages near and far from health
      facilities across four rural districts. Verbal consent was obtained. RESULTS:
      Respondents reported multiple, co-existing descriptions of causation including:
      contaminated water and difficulties accessing clean water; exposure to an unclean
      environment and poor food hygiene; contaminated breast milk due to sexual
      intercourse, overheated breast milk or bodily maternal conditions such as
      menstruation or pregnancy; and dietary imbalances and curses. Respondents rarely
      discussed the role of open defecation or the importance of handwashing with soap
      in preventing diarrhea. CONCLUSIONS: Categorizing behaviors as beneficial,
      harmful, non-existent or benign enables tailored programmatic recommendations.
      For example, respondents recognized the value of clean water and we
      correspondingly recommend interventions that reinforce consumption of and access
      to clean water. Second, respondents report denying "contaminated" breast milk to
      breastfeeding children. This is a harmful practice that merits attention. Third,
      the role of open defecation and poor hygiene in causing diarrhea is less
      understood and warrants introduction or clarification. Finally, the role of
      exposed feet or curses in causing diarrhea is relatively benign and does not
      necessitate programmatic attention. Further research supportive of communication
      and social mobilization strategies building on these findings is required to
      ensure that improved understanding regarding diarrhea causation translates into
      improved diarrhea prevention.

PMID- 24330587
TI  - Report on the 5'th scientific meeting of the "Verein zur Forderung des
      Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in
      Motzen, Germany, Oct. 25th - Oct. 27th, 2013.
AB  - From october 25th - 27th 2013, the 5th NEUROWIND e.V. meeting was held in Motzen,
      Brandenburg, Germany. This year more than 60 doctoral students and postdocs from
      over 25 different groups working in German university hospitals or research
      institutes attended the meeting to discuss their latest findings in the fields of
      neuroimmunology, neurodegeneration and neurovascular research. All participants
      appreciated the stimulating environment in Motzen, Brandenburg, and people took
      the opportunity for scientific exchange, discussion about ongoing projects and
      already started further collaborations. Like in the previous years, the symposium
      was regarded as a very well organized platform to support research of young
      investigators in Germany.According to the major aim of NEUROWIND e.V. to support
      younger researchers in Germany the 3rd NEUROWIND YOUNG SCIENTIST AWARD for
      experimental neurology was awarded to Ruth Stassart working in the group of Klaus
      Armin Nave and Wolfgang Bruck (MPI Gottingen and Department of Neuropathology,
      Gottingen Germany). The successful work was published in Nature Neuroscience
      entitled "A role for Swann cell-derived neuregulin-1 in remyelination". This
      outstanding paper deals with the function of Schwann cell neuregulin as an
      endogenous factor for myelin repair. The award is endowed with 20.000 Euro
      sponsored by Merck Serono GmbH, Darmstadt, Germany (unrestricted educational
      grant).This year's keynote lecture was given by Albert Ludolph, Head of the
      Department of Neurology at the University Clinic of Ulm. Dr. Ludolph highlighted
      the particular role of individual scientists for the development of research
      concepts in Alzheimer's disease (AD) and frontotemporal dementia (FTD). 

PMID- 24330588
TI  - An ongoing case-control study to evaluate the NHS breast screening programme.
AB  - BACKGROUND: In England, a national breast screening programme (NHSBSP) has been
      in place since 1988, and assessment of its impact on breast cancer incidence and
      mortality is essential to ensure that the programme is indeed doing more good
      than harm. This article describes large observation studies designed to estimate
      the effects of the current programme in terms of the benefits on breast cancer
      incidence and mortality and detrimental effect in terms of overdiagnosis. The
      case-control design of the cervical screening programme evaluation was highly
      effective in informing policy on screening intervals and age ranges. We propose
      innovative selection of cases and controls and gathering of additional variables
      to address new outcomes of interest and develop new methodologies to control for
      potential sources of bias. METHODS/DESIGN: Traditional case-control evaluation of
      breast screening uses women who have died from breast cancer as cases, and women
      known to be alive at the time of case death as controls. Breast screening
      histories prior to the cases' date of first diagnosis are compared. If breast
      screening is preventing mortality from breast cancer, cases will be characterised
      by a lesser screening history than controls. All deaths and incident cases of
      primary breast cancer in England within each 2-year study period will be included
      in this ongoing evaluation. Cases will be age- and area-matched to controls and
      variables related to cancer treatment and breast tumour pathology will be
      obtained to investigate the interplay between screening and treatment, and the
      effect of screening on incidence of advanced stage disease. Screening attendance
      at other national screening programmes will also be collected to derive superior
      adjustment for self-selection bias.The study is registered and has received full
      ethics approval.

PMID- 24330589
TI  - Renal mucinous tubular and spindle cell carcinoma: a report of 8 cases and review
      of the literature.
AB  - BACKGROUND: Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a
      rare variant of renal tumor. The current data show most of MTSCCs are of low
      malignant potential and rare cases metastatic to lymph nodes have been reported;
      however, the recorded computed tomography (CT) and follow up data are limited.
      MATERIAL AND METHOD: In the present study, we retrospectively analyzed CT and
      clinicopathological data of eight patients with renal MTSCC-K. RESULTS: A total
      of eight cases, including six females and two males, were included in this
      analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2
      (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were
      slightly enhanced on both corticomedullary and nephrographic phase, which was
      different from many other renal cell carcinomas. Three of them were treated with
      open radical nephrectomy, three with laparoscopic radical nephrectomy and the
      other two with laparoscopic partial nephrectomy. No postoperative therapy was
      applied. Patients were followed up for 15 to 64 months and there was no evidence
      of recurrence and metastasis. CONCLUSIONS: The MTSCC-K has special
      clinicopathological characteristics, low degree of malignancy and relative good
      prognosis. The diagnosis mainly depends on the histopathological examination and
      CT may help to differentiate with papillary renal cell carcinoma. Surgical
      treatment is recommended and additional therapies are not necessary. VIRTUAL
      SLIDES: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249.

PMID- 24330591
TI  - Hemolytic anemia associated with a novel heterozygote mutation 1183A in the PK-LR
      gene (PK- Jordan).

PMID- 24330590
TI  - Polysaccharides utilization in human gut bacterium Bacteroides thetaiotaomicron:
      comparative genomics reconstruction of metabolic and regulatory networks.
AB  - BACKGROUND: Bacteroides thetaiotaomicron, a predominant member of the human gut
      microbiota, is characterized by its ability to utilize a wide variety of
      polysaccharides using the extensive saccharolytic machinery that is controlled by
      an expanded repertoire of transcription factors (TFs). The availability of
      genomic sequences for multiple Bacteroides species opens an opportunity for their
      comparative analysis to enable characterization of their metabolic and regulatory
      networks. RESULTS: A comparative genomics approach was applied for the
      reconstruction and functional annotation of the carbohydrate utilization
      regulatory networks in 11 Bacteroides genomes. Bioinformatics analysis of
      promoter regions revealed putative DNA-binding motifs and regulons for 31
      orthologous TFs in the Bacteroides. Among the analyzed TFs there are 4 SusR-like
      regulators, 16 AraC-like hybrid two-component systems (HTCSs), and 11 regulators
      from other families. Novel DNA motifs of HTCSs and SusR-like regulators in the
      Bacteroides have the common structure of direct repeats with a long spacer
      between two conserved sites. CONCLUSIONS: The inferred regulatory network in B.
      thetaiotaomicron contains 308 genes encoding polysaccharide and sugar catabolic
      enzymes, carbohydrate-binding and transport systems, and TFs. The analyzed TFs
      control pathways for utilization of host and dietary glycans to monosaccharides
      and their further interconversions to intermediates of the central metabolism.
      The reconstructed regulatory network allowed us to suggest and refine specific
      functional assignments for sugar catabolic enzymes and transporters, providing a
      substantial improvement to the existing metabolic models for B. thetaiotaomicron.
      The obtained collection of reconstructed TF regulons is available in the
      RegPrecise database (http://regprecise.lbl.gov).

PMID- 24330592
TI  - Bohler's angle's role in assessing the injury severity and functional outcome of
      internal fixation for displaced intra-articular calcaneal fractures: a
      retrospective study.
AB  - BACKGROUND: Controversy exits over the role of Bohler's angle in assessing the
      injury severity of displaced intra-articular calcaneal fractures and predicting
      the functional outcome following internal fixation. This study aims to
      investigate whether a correlation exists between Bohler's angle and the injury
      severity of displaced calcaneal fractures, and between surgical improvement of
      Bohler's angle and functional outcome. METHODS: Patients treated operatively for
      unilateral closed displaced intra-articular calcaneal fractures from January 1,
      2004 to March 31, 2008 were identified. The Bohler's angles of both calcaneus
      were measured, and the measurement of the uninjured foot was used as its normal
      control. The difference in the value of Bohler's angle measured preoperatively or
      postoperatively between the angle of the injured foot and that of the
      contralateral calcaneus were calculated, respectively. The change in Bohler's
      angle by ratio was calculated by dividing the difference value of Bohler's angle
      between bilateral calcaneus by its normal control. The injury severity was
      assessed according to Sanders classification. The functional outcomes were
      assessed using American Orthopaedic Foot & Ankle Society hindfoot scores.
      RESULTS: 274 patients were included into the study with a mean follow-up duration
      of 71 months. According to Sanders classification, the fracture pattern included
      105 type II, 121 type III and 48 type IV fractures. According to American
      Orthopaedic Foot & Ankle Society hindfoot scoring system, the excellent, good,
      fair and poor results were achieved in 104, 132, 27, and 11 patients,
      respectively. The preoperative Bohler's angle, difference value of Bohler's angle
      between bilateral calcaneus, and change in Bohler's angle by ratio each has a
      significant correlation with Sanders classification (rs=-0.178, P=0.003; rs=
      0.174, P=0.004; rs=-0.172, P=0.005, respectively), however, is not correlated
      with functional outcome individually. The three postoperative measurements were
      all found to have a significant correlation with American Orthopaedic Foot &
      Ankle Society hindfoot scores (rs=0.223, P<0.001; rs=0.224, P<0.001; rs=0.220,
      P<0.001, respectively). However, these correlations were all weak to low.
      CONCLUSIONS: There was a significant correlation between preoperative Bohler's
      angle and the injury severity of displaced intra-articular calcaneal fractures,
      but only postoperative Bohler's angle parameters were found to have a significant
      correlation with the functional recovery.

PMID- 24330593
TI  - Multiple mechanisms underlying the long duration of action of thienorphine, a
      novel partial opioid agonist for the treatment of addiction.
AB  - AIMS: It is considered that a long-acting therapy would be advantageous in the
      treatment of addiction. In a search for novel buprenorphine analogues,
      thienorphine was demonstrated to be an extremely long-acting orally active
      partial opioid agonist. This study explored the mechanisms underlying the long
      lasting effects of thienorphine. METHODS: The binding kinetics of [(3)
      H]thienorphine were measured in membrane preparations expressing cloned rat
      opioid receptors. Flow cytometric analysis was used to determine the effect of
      thienorphine on the surface opioid receptor number. The long-lasting effects of
      thienorphine were also confirmed at the tissue level and in vivo. RESULTS: At 37
      degrees C, [(3) H]thienorphine showed rapid association with MU- and kappa-opioid
      receptors, while its dissociation was sluggish and biphasic (K-1 = 0.21 min(-1) ,
      K-2 = 0.0078 min(-1) for the MU-receptor; K-1 = 0.17 min(-1) , K-2 = 0.0042 min(
      1) for the kappa-receptor). Treatment with thienorphine for 24, 48, and 72 h
      downregulated surface MU-receptor in a dose- and time-dependent manner. The
      inhibitory effect of thienorphine on guinea pig ileum persisted for more than 120
      min after prolonged washing. In vivo, thienorphine exhibited significant
      antagonism of morphine-induced antinociception for more than 7 days. CONCLUSIONS:
      These results indicate that multiple factors, including persistent receptor
      occupation and enhanced receptor downregulation, may contribute to the long
      lasting effects of thienorphine that would be beneficial for its application in
      addiction treatment.

PMID- 24330594
TI  - Increasing teacher motivation and supervision is an important but not sufficient
      strategy for improving praziquantel uptake in Schistosoma mansoni control
      programs: serial cross sectional surveys in Uganda.
AB  - BACKGROUND: Realization of the public health benefits of mass drug administration
      (MDA) for the control of schistosomiasis depends on achieving and maintaining
      high annual treatment coverage. In Uganda, the uptake of preventive treatment for
      schistosomiasis among school-age children in 2011 was only 28%. Strategies are
      needed to increase uptake. METHODS: Serial cross-sectional surveys were conducted
      at baseline (after MDA in 2011) and at follow-up MDA in 2012 where teacher
      motivation was provided and supervision strengthened in Jinja district of Uganda.
      Uptake of praziquantel was assessed in 1,010 randomly selected children from 12
      primary schools during the baseline survey and in another set of 1,020 randomly
      selected children from the same primary schools during the follow-up survey.
      RESULTS: Self-reported uptake of praziquantel increased from 28.2% (95% CI 25.4%
      30.9%) at baseline to 48.9% (95% CI 45.8%-52.0%) (p < 0.001) at follow-up.
      Prevalence and intensity of Schistosoma mansoni infection were unchanged and
      moderate on both occasions; 35.0% (95% CI: 25.4%-37.9%) and 32.6% (95% CI: 29.6%
      35.5%) (p = 0.25) and 156.7 eggs per gram of stool (epg) (95% CI: 116.9-196.5)
      and 133.1 epg (95% CI: 99.0-167.2) (p = 0.38), respectively. There was no change
      in the proportion of children reporting side effects attributable to praziquantel
      at baseline (49.8%, 95% CI 43.8%-55.8%) and at follow-up (46.6%, 95% CI 42%.1
      51.2%) (p = 0.50) as well as in the proportion of children with correct knowledge
      of schistosomiasis transmission and control between the baseline (45.9%, 95% CI
      42.7%-73.7%) and follow-up (44.1%, 95% CI 41.0%- 47.2%) (p = 0.42). CONCLUSION:
      Although teacher motivation and supervision to distribute treatment increased the
      uptake of praziquantel among school-age children, the realized uptake is still
      lower than is recommended by the World Health Organization (WHO) and apparently
      too low to affect the prevalence and intensity of schistosomiasis among the
      children. Additional measures are needed to increase uptake of praziquantel if
      school-based MDA is to achieve the objective of preventive chemotherapy.

PMID- 24330595
TI  - The ovarian transcriptome of the cattle tick, Rhipicephalus (Boophilus)
      microplus, feeding upon a bovine host infected with Babesia bovis.
AB  - BACKGROUND: Cattle babesiosis is a tick-borne disease of cattle with the most
      severe form of the disease caused by the apicomplexan, Babesia bovis. Babesiosis
      is transmitted to cattle through the bite of infected cattle ticks of the genus
      Rhipicephalus. The most prevalent species is Rhipicephalus (Boophilus) microplus,
      which is distributed throughout the tropical and subtropical countries of the
      world. The transmission of B. bovis is transovarian and a previous study of the
      R. microplus ovarian proteome identified several R. microplus proteins that were
      differentially expressed in response to infection. Through various approaches, we
      studied the reaction of the R. microplus ovarian transcriptome in response to
      infection by B. bovis. METHODS: A group of ticks were allowed to feed on a B.
      bovis-infected splenectomized calf while a second group fed on an uninfected
      splenectomized control calf. RNA was purified from dissected adult female ovaries
      of both infected and uninfected ticks and a subtracted B. bovis-infected cDNA
      library was synthesized, subtracting with the uninfected ovarian RNA. Four
      thousand ESTs were sequenced from the ovary subtracted library and annotated.
      RESULTS: The subtracted library dataset assembled into 727 unique contigs and
      2,161 singletons for a total of 2,888 unigenes, Microarray experiments designed
      to detect B. bovis-induced gene expression changes indicated at least 15
      transcripts were expressed at a higher level in ovaries from ticks feeding upon
      the B. bovis-infected calf as compared with ovaries from ticks feeding on an
      uninfected calf. We did not detect any transcripts from these microarray
      experiments that were expressed at a lower level in the infected ovaries compared
      with the uninfected ovaries. Using the technique called serial analysis of gene
      expression, 41 ovarian transcripts from infected ticks were differentially
      expressed when compared with transcripts of controls. CONCLUSION: Collectively,
      our experimental approaches provide the first comprehensive profile of the R.
      microplus ovarian transcriptome responding to infection by B. bovis. This dataset
      should prove useful in molecular studies of host-pathogen interactions between
      this tick and its apicomplexan parasite.

PMID- 24330596
TI  - Topological insulator metamaterials with tunable negative refractive index in the
      optical region.
AB  - A blueshift tunable metamaterial (MM) exhibiting a double-negative refractive
      index based on a topological insulator (bismuth selenide, Bi2Se3) has been
      demonstrated in the near-infrared (NIR) spectral region. The potential of Bi2Se3
      as a dielectric interlayer of the multilayer MM is explored. The optical response
      of elliptical nanohole arrays penetrating through Au/Bi2Se3/Au films is
      numerically investigated using the finite difference time domain (FDTD) method.
      The blueshift tuning range of the MM is as high as 370 nm (from 2,140 to 1,770
      nm) after switching the Bi2Se3 between its trigonal and orthorhombic states. 

PMID- 24330597
TI  - Metabolic syndrome in HIV-infected individuals: underlying mechanisms and
      epidemiological aspects.
AB  - The success of highly active antiretroviral therapy (HAART) has determined a
      dramatic decline in AIDS- and immunodeficiency-related causes of death in the HIV
      infected population. As life-expectancy increases, such individuals have become
      gradually exposed not only to the effects of aging itself, but also to the
      influence of environmental risk factors, which are known to act in the general
      population. These features can lead to obesity, diabetes mellitus and ultimately
      cardiovascular diseases (CVD). Metabolic complications and abnormal fat
      distribution were frequently observed after a few years of antiretroviral therapy
      and, as the array of antiretroviral drugs became broader, long term metabolic
      alterations are becoming far more common worldwide. Nevertheless, the risk of not
      being on HAART is overwhelmingly greater than the metabolic adverse events in
      terms of morbidity and mortality events. HIV/HAART-induced metabolic unbalances
      overlap in some extent the components of Metabolic Syndrome (MetS) and its high
      rates in the HIV population place infected individuals in an elevated CVD risk
      category. MetS can explain at least in part the emergence of CVD as the major
      morbidity and mortality conditions in the HIV population. In this review we
      convey information on the underlying aspects of MetS during HIV infection,
      highlighting some physiopathological and epidemiological features of this
      comorbidity along with the role played by HIV itself and the synergy action of
      some antiretroviral drugs. Considerations on MetS management in the HIV
      population are also depicted. 

PMID- 24330598
TI  - Design, synthesis and biological evaluation of pyridin-3-yl pyrimidines as potent
      Bcr-Abl inhibitors.
AB  - A series of pyridin-3-yl pyrimidines was synthesized and evaluated for their Bcr
      Abl inhibitory and anticancer activity. The preliminary results indicated that
      some compounds were promising anticancer agents. Compounds A2, A8, and A9
      exhibited potent Bcr-Abl inhibitory activity, suggesting that aniline containing
      halogen substituents might be important for biological activity. Molecular
      docking was carried out to investigate the binding mode of them with Bcr-Abl.
      Details of synthesis and SAR studies of these compounds are described. 

PMID- 24330599
TI  - c-Jun N-terminal kinase in synergistic neurite outgrowth in PC12 cells mediated
      through P90RSK.
AB  - BACKGROUND: Synergistic multi-ligand treatments that can induce neuronal
      differentiation offer valuable strategies to regulate and modulate neurite
      outgrowth. Whereas the signaling pathways mediating single ligand-induced neurite
      outgrowth, such as Akt, extracellular signal-regulated kinase (Erk), c-Jun N
      terminal kinase (JNK), and p38 mitogen-activated protein kinase (P38), have been
      extensively studied, the mechanisms underlying multi-ligand synergistic neurite
      outgrowth are poorly understood. In an attempt to gain insight into synergistic
      neurite outgrowth, PC12 cells were treated with one of three combinations:
      pituitary adenylate cyclase-activating peptide (PACAP) with epidermal growth
      factor (EP), basic fibroblast growth factor (FP), or nerve growth factor (NP) and
      then challenged with the appropriate kinase inhibitors to assess the signaling
      pathways involved in the process. RESULTS: Response surface analyses indicated
      that synergistic neurite outgrowth was regulated by distinct pathways in these
      systems. Synergistic increases in the phosphorylation of Erk and JNK, but not Akt
      or P38, were observed with the three growth factor-PACAP combinations.
      Unexpectedly, we identified a synergistic increase in JNK phosphorylation, which
      was involved in neurite outgrowth in the NP and FP, but not EP, systems.
      Inhibition of JNK using the SP600125 inhibitor reduced phosphorylation of 90 kDa
      ribosomal S6 kinase (P90RSK) in the NP and FP, but not EP, systems. This
      suggested the involvement of P90RSK in mediating the differential effects of JNK
      in synergistic neurite outgrowth. CONCLUSIONS: Taken together, these findings
      reveal the involvement of distinct signaling pathways in regulating neurite
      outgrowth in response to different synergistic growth factor-PACAP treatments.
      Our findings demonstrate a hitherto unrecognized mechanism of JNK-P90RSK in
      mediating synergistic neurite outgrowth induced by the co-treatment of growth
      factors and PACAP.

PMID- 24330600
TI  - Construction and utilization of a script concordance test as an assessment tool
      for DCEM3 (5th year) medical students in rheumatology.
AB  - BACKGROUND: The script concordance test (SCT) is a method for assessing clinical
      reasoning of medical students by placing them in a context of uncertainty such as
      they will encounter in their future daily practice. Script concordance testing is
      going to be included as part of the computer-based national ranking examination
      (iNRE).This study was designed to create a script concordance test in
      rheumatology and use it for DCEM3 (fifth year) medical students administered via
      the online platform of the Clermont-Ferrand medical school. METHODS: Our SCT for
      rheumatology teaching was constructed by a panel of 19 experts in rheumatology (6
      hospital-based and 13 community-based). One hundred seventy-nine DCEM3 (fifth
      year) medical students were invited to take the test. Scores were computed using
      the scoring key available on the University of Montreal website. Reliability of
      the test was estimated by the Cronbach alpha coefficient for internal
      consistency. RESULTS: The test comprised 60 questions. Among the 26 students who
      took the test (26/179: 14.5%), 15 completed it in its entirety. The reference
      panel of rheumatologists obtained a mean score of 76.6 and the 15 students had a
      mean score of 61.5 (p = 0.001). The Cronbach alpha value was 0.82. CONCLUSIONS:
      An online SCT can be used as an assessment tool for medical students in
      rheumatology. This study also highlights the active participation of community
      based rheumatologists, who accounted for the majority of the 19 experts in the
      reference panel.A script concordance test in rheumatology for 5th year medical
      students.

PMID- 24330601
TI  - Reducing length of stay for acute diabetic foot episodes: employing an extended
      scope of practice podiatric high-risk foot coordinator in an acute foundation
      trust hospital.
AB  - BACKGROUND: To enhance the acute management of people with diabetic foot disease
      requiring admission, an extended scope of practice, podiatric high-risk foot
      coordinator position, was established at the Great Western Hospital, Swindon in
      2010. The focus of this new role was to facilitate more efficient and timely
      management of people with complex diabetic foot disease. The aim of this project
      was to investigate the impact of the podiatric high-risk foot coordinator role on
      length of stay, rate of re-admission and bed cost. METHOD: This study evaluated
      the difference in length of stay and rate of re-admission between an 11- month
      pre-pilot period (November 2008 to October 2009) and a 10-month pilot period
      (August 2010 to June 2011). The estimated difference in bed cost between the pre
      pilot and pilot audits was also calculated. Inclusion criteria were restricted to
      inpatients admitted with a diabetic foot ulcer, gangrene, cellulitis or infection
      as the primary cause for admission. Eligible records were retrieved using ICD-10
      (V9) coding via the hospital clinical audit department for the pre-pilot period
      and a unique database was used to source records for the pilot phase. RESULTS:
      Following the introduction of the podiatric high-risk foot coordinator, the
      average length of stay reduced from 33.7 days to 23.3 days (mean difference 10.4
      days, 95% CI 0.0 to 20.8, p = 0.050). There was no statistically significant
      difference in re-admission rate between the two study periods, 17.2% (95% CI
      12.2% to 23.9%) in the pre-pilot phase and 15.4% (95% CI 12.0% to 19.5%) in the
      pilot phase (p = 0.820). The extrapolated annual cost saving following the
      implementation of the new coordinator role was calculated to be L234,000 for the
      2010/2011 year. CONCLUSIONS: This audit found that the extended scope of practice
      coordinator role may have a positive impact on reducing length of stay for
      diabetic foot admissions. This paper advocates the role of a podiatric high-risk
      foot coordinator utilising an extended scope of practice model, although further
      research is needed.

PMID- 24330602
TI  - The environment ontology: contextualising biological and biomedical entities.
AB  - As biological and biomedical research increasingly reference the environmental
      context of the biological entities under study, the need for formalisation and
      standardisation of environment descriptors is growing. The Environment Ontology
      (ENVO; http://www.environmentontology.org) is a community-led, open project which
      seeks to provide an ontology for specifying a wide range of environments relevant
      to multiple life science disciplines and, through an open participation model, to
      accommodate the terminological requirements of all those needing to annotate data
      using ontology classes. This paper summarises ENVO's motivation, content,
      structure, adoption, and governance approach. The ontology is available from
      http://purl.obolibrary.org/obo/envo.owl - an OBO format version is also available
      by switching the file suffix to "obo". 

PMID- 24330603
TI  - The value of survival analyses for evidence-based rural medical workforce
      planning.
AB  - BACKGROUND: Globally, abundant opportunities exist for policymakers to improve
      the accessibility of rural and remote populations to primary health care through
      improving workforce retention. This paper aims to identify and quantify the most
      important factors associated with rural and remote Australian family physician
      turnover, and to demonstrate how evidence generated by survival analysis of
      health workforce data can inform rural workforce policy making. METHODS: A
      secondary analysis of longitudinal data collected by the New South Wales (NSW)
      Rural Doctors Network for all family physicians working in rural or remote NSW
      between January 1(st) 2003 and December 31(st) 2012 was performed. The Prentice,
      Williams and Peterson statistical model for survival analysis was used to
      identify and quantify risk factors for rural NSW family physician turnover.
      RESULTS: Multivariate modelling revealed a higher (2.65-fold) risk of family
      physician turnover in small, remote locations compared to that in small closely
      settled locations. Family physicians who graduated from countries other than
      Australia, United Kingdom, United States of America, New Zealand, Ireland, and
      Canada also had a higher (1.45-fold) risk of turnover compared to Australian
      trained family physicians. This was after adjusting for the effects of
      conditional registration. Procedural skills and public hospital admitting rights
      were associated with a lower risk of turnover. These risks translate to a
      predicted median survival of 11 years for Australian-trained family physician non
      proceduralists with hospital admitting rights working in small coastal closely
      settled locations compared to 3 years for family physicians in remote locations.
      CONCLUSIONS: This study provides rigorous empirical evidence of the strong
      association between population size and geographical location and the retention
      of family physicians in rural and remote NSW. This has important policy
      ramifications since retention grants for rural and remote family physicians in
      Australia are currently based on a geographical 'remoteness' classification
      rather than population size. In addition, this study demonstrates how survival
      analysis assists health workforce planning, such as through generating evidence
      to assist in benchmarking 'reasonable' lengths of practice in different
      geographic settings that might guide service obligation requirements.

PMID- 24330604
TI  - Improving Adherence Physical Activity with a Smartphone Application Based on
      Adults with Intellectual Disabilities (APPCOID).
AB  - BACKGROUND: People with intellectual disabilities (ID) have lower levels of
      physical activity and quality of life and they have a lot of barriers to face
      when taking part in physical activity. Other problems are the poor adherence to
      physical activity such people have so this study is designed to improve adherence
      to physical activity for people with intellectual disabilities with the
      assistance of an application for smartphones. The aim of the study will be to
      improve physical activity and physical condition after multimodal intervention
      and to analyse the promotion of adherence to physical activity through a
      multimodal intervention and an app intervention (mHealth) in people with ID.
      METHODS: A two-stage study will be conducted. In stage 1 a multimodal
      intervention will take place will be done with physical activity and educational
      advice over eight weeks, two days a week. Data will be measured after and before
      the intervention. In stage 2 a randomized controlled trial will be conducted. In
      the intervention group we will install an application to a smartphone; this
      application will be a reminder to do a physical activity and they have to select
      whether they have or haven't done a physical activity every day. This application
      will be installed for 18 weeks. Data will be measured after and before the
      application is installed in two groups. We will measure results 10 weeks later
      when the two groups don't have the reminder. The principal outcome used to
      measure the adherence to physical activity will be the International Physical
      Activity Questionnaire; secondary outcomes will be a fun-fitness test and self
      report survey about quality of life, self-efficacy and social support. Samples
      will be randomized by sealed envelope in two groups, with approximately 20
      subjects in each group. It's important to know that the therapist will be blinded
      and won't know the subjects of each group. DISCUSSION: Offering people with ID a
      multimodal intervention and tool to increase the adherence to a physical activity
      may increase the levels of physical activity and quality of life. Such a scheme,
      if beneficial, could be implemented successfully within public health sense.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01915381.

PMID- 24330605
TI  - Improving lactose digestion and symptoms of lactose intolerance with a novel
      galacto-oligosaccharide (RP-G28): a randomized, double-blind clinical trial.
AB  - BACKGROUND: Lactose intolerance (LI) is a common medical problem with limited
      treatment options. The primary symptoms are abdominal pain, diarrhea, bloating,
      flatulence, and cramping. Limiting dairy foods to reduce symptoms contributes to
      low calcium intake and the risk for chronic disease. Adaptation of the colon
      bacteria to effectively metabolize lactose is a novel and potentially useful
      approach to improve lactose digestion and tolerance. RP-G28 is novel galacto
      oligosaccharide (GOS) being investigated to improve lactose digestion and the
      symptoms of lactose intolerance in affected patients. METHODS: A randomized,
      double-blind, parallel group, placebo-controlled study was conducted at 2 sites
      in the United States. RP-G28 or placebo was administered to 85 patients with LI
      for 35 days. Post-treatment, subjects reintroduced dairy into their daily diets
      and were followed for 30 additional days to evaluate lactose digestion as
      measured by hydrogen production and symptom improvements via a patient-reported
      symptom assessment instrument. RESULTS: Lactose digestion and symptoms of LI
      trended toward improvement on RP-G28 at the end of treatment and 30 days post
      treatment. A reduction in abdominal pain was also demonstrated in the study
      results. Fifty percent of RP-G28 subjects with abdominal pain at baseline
      reported no abdominal pain at the end of treatment and 30 days post treatment (p
      = 0.0190). RP-G28 subjects were also six times more likely to claim lactose
      tolerance post-treatment once dairy foods had been re-introduced into their diets
      (p = 0.0389). CONCLUSIONS: Efficacy trends and favorable safety/tolerability
      findings suggest that RP-G28 appears to be a potentially useful approach for
      improving lactose digestion and LI symptoms. The concurrent reduction in
      abdominal pain and improved overall tolerance could be a meaningful benefit to
      lactose intolerant individuals.

PMID- 24330606
TI  - Immunohistochemial study on the expression of von Willebrand factor (vWF) after
      onlay autogenous iliac grafts for lateral alveolar ridge augmentation.
AB  - INTRODUCTION: The main problems of autogenous bone transplants are their
      unpredictable atrophy and their loss of structure. One key factor lies in the
      poor revascularization of simple onlay grafts. The the aim of this study was to
      evaluate the revascularization processes in autogenous bone grafts from the iliac
      crest to the alveolar ridge. METHODS: In a sheep model, autogenous bone grafts
      were harvested from the iliac crest. A combination of a resorbable collagen
      membrane (CM) and deproteinized bovine bone material (DBBM) was used to modify
      the bone graft (experiment 2). This was compared with a simple onlay bone graft
      (control group, experiment 1). The amount of vessels in bone and connective
      tissue (CT), and the amount of CT were analyzed. The expression of von Willebrand
      factor (vWF) was compared between the two experimental groups using
      immunohistochemical analysis. RESULTS: The ratio of the amount of vessels in bone
      and CT changed over time, and more vessels could be detected in bone at 12-16
      weeks of graft healing. The number of vessels were significantly higher in
      experiment 2 than in experiment 1. More CT was found in experiment 1, whereas the
      amount of CT in both experiments decreased over time. CONCLUSION: This study
      shows a more intensive and extensive revascularization in experiment 2, as
      significantly more vessels were detected. The decreased amount of CT in
      experiment 2 clarifies its clinical superiority.

PMID- 24330607
TI  - High epiregulin expression in human U87 glioma cells relies on IRE1alpha and
      promotes autocrine growth through EGF receptor.
AB  - BACKGROUND: Epidermal growth factor (EGF) receptors contribute to the development
      of malignant glioma. Here we considered the possible implication of the EGFR
      ligand epiregulin (EREG) in glioma development in relation to the activity of the
      unfolded protein response (UPR) sensor IRE1alpha. We also examined EREG status in
      several glioblastoma cell lines and in malignant glioma. METHODS: Expression and
      biological properties of EREG were analyzed in human glioma cells in vitro and in
      human tumor xenografts with regard to the presence of ErbB proteins and to the
      blockade of IRE1alpha. Inactivation of IRE1alpha was achieved by using either the
      dominant-negative strategy or siRNA-mediated knockdown. RESULTS: EREG was
      secreted in high amounts by U87 cells, which also expressed its cognate EGF
      receptor (ErbB1). A stimulatory autocrine loop mediated by EREG was evidenced by
      the decrease in cell proliferation using specific blocking antibodies directed
      against either ErbB1 (cetuximab) or EREG itself. In comparison, anti-ErbB2
      antibodies (trastuzumab) had no significant effect. Inhibition of IRE1alpha
      dramatically reduced EREG expression both in cell culture and in human xenograft
      tumor models. The high-expression rate of EREG in U87 cells was therefore linked
      to IRE1alpha, although being modestly affected by chemical inducers of the
      endoplasmic reticulum stress. In addition, IRE1-mediated production of EREG did
      not depend on IRE1 RNase domain, as neither the selective dominant-negative
      invalidation of the RNase activity (IRE1 kinase active) nor the siRNA-mediated
      knockdown of XBP1 had significant effect on EREG expression. Finally, chemical
      inhibition of c-Jun N-terminal kinases (JNK) using the SP600125 compound reduced
      the ability of cells to express EREG, demonstrating a link between the growth
      factor production and JNK activation under the dependence of IRE1alpha.
      CONCLUSION: EREG may contribute to glioma progression under the control of
      IRE1alpha, as exemplified here by the autocrine proliferation loop mediated in
      U87 cells by the growth factor through ErbB1.

PMID- 24330608
TI  - Detoxification and stress response genes expressed in a western North American
      bumble bee, Bombus huntii (Hymenoptera: Apidae).
AB  - BACKGROUND: The Hunt bumble bee (Bombus huntii Greene, Hymenoptera: Apidae) is a
      holometabolous, social insect important as a pollinator in natural and
      agricultural ecosystems in western North America. Bumble bees spend a significant
      amount of time foraging on a wide variety of flowering plants, and this activity
      exposes them to both plant toxins and pesticides, posing a threat to individual
      and colony survival. Little is known about what detoxification pathways are
      active in bumble bees, how the expression of detoxification genes changes across
      life stages, or how the number of detoxification genes expressed in B. huntii
      compares to other insects. RESULTS: We found B. huntii expressed at least 584
      genes associated with detoxification and stress responses. The expression levels
      of some of these genes, such as those encoding the cytochrome P450s, glutathione
      S-transferases (GSTs) and glycosidases, vary among different life stages to a
      greater extent than do other genes. We also found that the number of P450s, GSTs
      and esterase genes expressed by B. huntii is similar to the number of these genes
      found in the genomes of other bees, namely Bombus terrestris, Bombus impatiens,
      Apis mellifera and Megachile rotundata, but many fewer than are found in the fly
      Drosophila melanogaster. CONCLUSIONS: Bombus huntii has transcripts for a large
      number of detoxification and stress related proteins, including oxidation and
      reduction enzymes, conjugation enzymes, hydrolytic enzymes, ABC transporters,
      cadherins, and heat shock proteins. The diversity of genes expressed within some
      detoxification pathways varies among the life stages and castes, and we typically
      identified more genes in the adult females than in larvae, pupae, or adult males,
      for most pathways. Meanwhile, we found the numbers of detoxification and stress
      genes expressed by B. huntii to be more similar to other bees than to the fruit
      fly. The low number of detoxification genes, first noted in the honey bee,
      appears to be a common phenomenon among bees, and perhaps results from their
      symbiotic relationship with plants. Many flowering plants benefit from
      pollinators, and thus offer these insects rewards (such as nectar) rather than
      defensive plant toxins.

PMID- 24330609
TI  - A prospective study: inflammation, infection and comorbidity in patients on long
      term dialysis.
AB  - BACKGROUND: The goal of this study was to identify inflammatory and infectious
      markers and their roles in mortality. METHODS: We enrolled 111 patients on
      haemodialysis (HD) and collected data at three time points (baseline, 33 and 76
      months). RESULTS: Rates of Chlamydophila pneumoniae IgG, CRP >=3 mg/l, ESR >50
      mm/hour and fibrinogen >4 g/l were, respectively, 63.1%, 60.4%, 48.6% and 42.3%.
      Mortality was 21.6% and 43.2% at 33 and 76 months where 58.3% of all deaths were
      cardiocerebrovascular (CCV) related. Non-survivors were older than survivors.
      Univariate analysis showed diabetes mellitus (DM) and cerebrovascular accident
      (CVA) as important for the 33-month all-cause mortality, and CRPlog , fibrinogen,
      ESR >50 mm/hour, cardiovascular disease (CVD) and DM for the 76-month all-cause
      mortality. CVA was meaningful for the 33-month CCV mortality, and CVD, DM and ESR
      >50 mm/hour for the 76-month CCV mortality. Kaplan-Meier revealed poorer survival
      for patients with ESR >50 mm/hour at 76 months. Cox regression showed CVD, CVA
      and age as mortality predictors. CONCLUSION: Age, CVD and CVA are predictors for
      mortality in patients on HD patients, but the presence of C. pneumoniae IgG and
      inflammation are not.

PMID- 24330610
TI  - Histological remodelling of demineralised bone matrix allograft in posterolateral
      fusion of the spine--an ex vivo study.
AB  - BACKGROUND: Demineralised bone matrix (DBM) has shown to be effective in
      enhancing posterior fusion of the spine. Several animal studies and clinical
      investigations in humans showed its successful remodelling. The use of allogenic
      matrix may decrease the need of autologous bone graft and therefore helps prevent
      corresponding donor site morbidity. Since DBM products are very expensive, the
      question arises, whether it is completely remodelled into new bone, and therefore
      truly is comparable to autologous cancellous bone graft. To our knowledge there
      is no report of a consecutive series of patients where ex vivo histological
      analysis after postero-lateral fusion of the spine was performed. METHODS:
      Osseous biopsies of nine consecutive patients who underwent postero-lateral
      fusion of the spine for trauma were obtained at the time of elective removal of
      the hardware. Histological samples were then analyzed on ground and thin sections
      stained with toluidine blue and von Kossa stainings. RESULTS: Time span between
      index operation and removal of the metal ranged between 6 and 18 month.
      Histological analysis showed good incorporation and overall remodelling of DBM
      into new bone in all patients. No foreign body reaction was visible and new bone
      formation progressed time dependently with DBM in situ. Four out of nine patients
      showed more than 50% new bone formation after one year. CONCLUSION: DBM shows
      good overall remodelling properties in histological analysis and therefore seems
      to be an effective adjunct in postero-lateral fusion of the spine. Furthermore,
      DBM substitution increases over time.

PMID- 24330611
TI  - Network based elucidation of drug response: from modulators to targets.
AB  - : Network-based drug discovery aims at harnessing the power of networks to
      investigate the mechanism of action of existing drugs, or new molecules, in order
      to identify innovative therapeutic treatments. In this review, we describe some
      of the most recent advances in the field of network pharmacology, starting with
      approaches relying on computational models of transcriptional networks, then
      moving to protein and signaling network models and concluding with "drug
      networks". These networks are derived from different sources of experimental
      data, or literature-based analysis, and provide a complementary view of drug mode
      of action. Molecular and drug networks are powerful integrated computational and
      experimental approaches that will likely speed up and improve the drug discovery
      process, once fully integrated into the academic and industrial drug discovery
      pipeline. 

PMID- 24330612
TI  - Gene and cytokine profile analysis of macrolide-resistant Mycoplasma pneumoniae
      infection in Fukuoka, Japan.
AB  - BACKGROUND: Recent epidemiologic data suggest that the prevalence of macrolide
      resistant Mycoplasma pneumoniae (MR-M. pneumoniae) is increasing rapidly
      worldwide. This study assessed the present status of M. pneumoniae infection in
      Japan and clinical end-points to distinguish children with MR-M. pneumoniae.
      METHODS: During an outbreak of M. pneumoniae infections in Fukuoka, Japan in 2010
      11, a total of 105 children with clinically suspected M. pneumoniae infection
      were enrolled. M. pneumoniae was analyzed for macrolide resistance in domain V of
      the 23S rRNA gene. Sixty -five patients with PCR positive for M. pneumoniae were
      analyzed with regard to clinical symptoms, efficacy of several antimicrobial
      agents and several laboratory data. RESULTS: Causative pathogens were detected in
      81.0% (85 of 105) and M. pneumoniae was identified 61.9% (65 of 105). The
      resistance rate of M. pneumoniae was 89.2% (58 of 65) in this general pediatric
      outpatient setting. Patients infected with MR-M. pneumoniae showed longer times
      to resolution of fever and required frequent changes of the initially prescribed
      macrolide to another antimicrobial agent. We observed three different genotypes
      of M. pneumoniae including the rarely reported A2063T mutation (A2063G: 31
      strains, A2063T: 27 strains, no mutation: 7 strains). Drug susceptibility testing
      showed different antimicrobial susceptibility profiles for each genotype. Serum
      IFN-gamma, IL-6 and IP-10 levels were higher in patients with MR-genotypes than
      in those infected with no-mutation strains (p < 0.001). CONCLUSIONS: Macrolide
      resistance is more common than previously thought and a small epidemic of rarely
      reported A2063T mutation was observed in Fukuoka, Japan. Furthermore our results
      reveal the possibility that levels of certain inflammatory cytokines may be a
      candidate to predict MR-M.pneumoniae infection.

PMID- 24330613
TI  - A new radiographic view of the hindfoot.
AB  - BACKGROUND: A new radiographic view was proposed to evaluate the coronal plane
      alignment of the hindfoot under weightbearing conditions. METHODS: We studied 46
      feet of individuals with normal appearing asymptomatic feet. On the antero
      posterior roentgenogram using this new method, the line from the top of the
      sustentaculum tali to the lateral-inferior end of the posterior articular surface
      of the talus was obtained as the standard line showing varus or valgus of the
      calcaneus. We defined the angle between the longitudinal axis of the tibia and
      the standard line as described above as Varus-Valgus angle (V-V angle). RESULTS:
      The mean (+/-SD) V-V angle of the 46 feet studied was 76.4 (+/-3.6) degrees.
      CONCLUSION: The findings from this study indicate that it is possible to estimate
      the alignment of the hindfoot quantitatively by comparing individuals to the mean
      V-V angle that we calculated in our sample, which was 76.4 degrees.

PMID- 24330614
TI  - Stronger pack warnings predict quitting more than weaker ones: finding from the
      ITC Malaysia and Thailand surveys.
AB  - BACKGROUND: We examined the impact of cigarette pack warning labels on interest
      in quitting and subsequent quit attempts among adult smokers in Malaysia and
      Thailand. METHODS: Two overlapping cohorts of adults who reported smoking factory
      made cigarettes from Malaysia and Thailand were interviewed face-to-face (3189
      were surveyed at baseline and 1781 re-contacted at Wave 2; 2361 current smokers
      were surveyed at Wave 2 and 1586 re-contacted at Wave 3). In Thailand at
      baseline, large text only warnings were assessed, while at Wave 2 new large
      graphic warnings were assessed. In Malaysia, during both waves small text only
      warnings were in effect. Reactions were used to predict interest in quitting, and
      to predict making quit attempts over the following inter-wave interval. RESULTS:
      Multivariate predictors of "interest in quitting" were comparable across
      countries, but predictors of quit attempts varied. In both countries, cognitive
      reactions to warnings (adjusted ORs; 1.57 & 1.69 for Malaysia at wave 1 and wave
      2 respectively and 1.29 & 1.19 for Thailand at wave 1 and wave 2 respectively),
      forgoing a cigarette (except Wave 2 in Malaysia) (adjusted ORs; 1.77 for Malaysia
      at wave 1 and 1.54 & 2.32 for Thailand at wave 1 and wave 2 respectively), and
      baseline knowledge (except wave 2 in both countries) (adjusted ORs; 1.71 & 1.51
      for Malaysia and Thailand respectively) were positively associated with interest
      in quitting at that wave. In Thailand only, "cognitive reactions to warnings"
      (adjusted ORs; 1.12 & 1.23 at wave 1 and wave 2 respectively), "forgoing a
      cigarette" (adjusted OR = 1.55 at wave 2 only) and "an interest in quitting"
      (adjusted ORs; 1.61 & 2.85 at wave 1 and wave 2 respectively) were positively
      associated with quit attempts over the following inter-wave interval. Salience
      was negatively associated with subsequent quit attempts in both Malaysia and
      Thailand, but at Wave 2 only (adjusted ORs; 0.89 & 0.88 for Malaysia and Thailand
      respectively). CONCLUSION: Warnings appear to have common mechanisms for
      influencing quitting regardless of warning strength. The larger and more
      informative Thai warnings were associated with higher levels of reactions
      predictive of quitting and stronger associations with subsequent quitting,
      demonstrating their greater potency.

PMID- 24330616
TI  - Implementing large-scale workforce change: learning from 55 pilot sites of allied
      health workforce redesign in Queensland, Australia.
AB  - BACKGROUND: Increasingly, health workforces are undergoing high-level 're
      engineering' to help them better meet the needs of the population, workforce and
      service delivery. Queensland Health implemented a large scale 5-year workforce
      redesign program across more than 13 health-care disciplines. This study
      synthesized the findings from this program to identify and codify mechanisms
      associated with successful workforce redesign to help inform other large
      workforce projects. METHODS: This study used Inductive Logic Reasoning (ILR), a
      process that uses logic models as the primary functional tool to develop theories
      of change, which are subsequently validated through proposition testing. Initial
      theories of change were developed from a systematic review of the literature and
      synthesized using a logic model. These theories of change were then developed
      into propositions and subsequently tested empirically against documentary,
      interview, and survey data from 55 projects in the workforce redesign program.
      RESULTS: Three overarching principles were identified that optimized successful
      workforce redesign: (1) drivers for change need to be close to practice; (2)
      contexts need to be supportive both at the local levels and legislatively; and
      (3) mechanisms should include appropriate engagement, resources to facilitate
      change management, governance, and support structures. Attendance to these
      factors was uniformly associated with success of individual projects.
      CONCLUSIONS: ILR is a transparent and reproducible method for developing and
      testing theories of workforce change. Despite the heterogeneity of projects,
      professions, and approaches used, a consistent set of overarching principles
      underpinned success of workforce change interventions. These concepts have been
      operationalized into a workforce change checklist.

PMID- 24330615
TI  - Temporal and micro-spatial heterogeneity in the distribution of Anopheles vectors
      of malaria along the Kenyan coast.
AB  - BACKGROUND: The distribution of anopheline mosquitoes is determined by temporally
      dynamic environmental and human-associated variables, operating over a range of
      spatial scales. Macro-spatial short-term trends are driven predominantly by prior
      (lagged) seasonal changes in climate, which regulate the abundance of suitable
      aquatic larval habitats. Micro-spatial distribution is determined by the location
      of these habitats, proximity and abundance of available human bloodmeals and
      prevailing micro-climatic conditions. The challenge of analysing--in a single
      coherent statistical framework--the lagged and distributed effect of seasonal
      climate changes simultaneously with the effects of an underlying hierarchy of
      spatial factors has hitherto not been addressed. METHODS: Data on Anopheles
      gambiae sensu stricto and A. funestus collected from households in Kilifi
      district, Kenya, were analysed using polynomial distributed lag generalized
      linear mixed models (PDL GLMMs). RESULTS: Anopheline density was positively and
      significantly associated with amount of rainfall between 4 to 47 days, negatively
      and significantly associated with maximum daily temperature between 5 and 35
      days, and positively and significantly associated with maximum daily temperature
      between 29 and 48 days in the past (depending on Anopheles species). Multiple
      occupancy households harboured greater mosquito numbers than single-occupancy
      households. A significant degree of mosquito clustering within households was
      identified. CONCLUSIONS: The PDL GLMMs developed here represent a generalizable
      framework for analysing hierarchically-structured data in combination with
      explanatory variables which elicit lagged effects. The framework is a valuable
      tool for facilitating detailed understanding of determinants of the spatio
      temporal distribution of Anopheles. Such understanding facilitates delivery of
      targeted, cost-effective and, in certain circumstances, preventative
      antivectorial interventions against malaria.

PMID- 24330617
TI  - Antiretroviral regimens sparing agents from the nucleoside(tide) reverse
      transcriptase inhibitor class: a review of the recent literature.
AB  - The nucleoside(tide) reverse transcriptase inhibitors (NRTIs) have traditionally
      been an important 'back-bone' of an antiretroviral therapy (ART) regimen. However
      all agents have been associated with both short- and long-term toxicity. There
      have also been concerns regarding the efficacy and safety of a treatment
      sequencing strategy in which those with past exposure and/or resistance to one or
      more NRTIs are re-exposed to 'recycled' NRTIs in subsequent ART regimens. Newer,
      potent and possible safer, agents from various ART classes continue to become
      available. There has therefore been growing interest in evaluating NRTI-sparing
      regimens. In this review, we examined studies of NRTI-sparing regimens in adult
      HIV-positive patients with varying degrees of ART experience. We found that in
      treatment experienced patients currently on a failing regimen with detectable
      viral load, there now exists a robust evidence for the use of NRTI-sparing
      regimens including raltegravir with a boosted-protease inhibitor with or without
      a third agent. In those on a virologically suppressive regimen switching to a
      NRTI-sparing regimen or in those ART-naive patients initiating an NRTI-sparing
      regimen, evidence is sparse and largely comes from small exploratory trials or
      observational studies. Overall, these studies suggest that caution needs to be
      exercised in carefully selecting the right candidate and agents, especially in
      the context of a dual-therapy regimen, to minimise the risks of virological
      failure. There is residual toxicity conferred by the ritonavir boost in protease
      inhibitor containing NRTI-sparing regimens. Fully-powered studies are needed to
      explore the place of N (t)RTI-sparing regimens in the sequencing of ART.
      Additionally research is required to explore how to minimise the adverse effects
      associated with ritonavir-based pharmacoenhancement. 

PMID- 24330618
TI  - Simultaneous rearrangements of TAL1 and LMO2 in T-cell acute lymphoblastic
      leukemia.

PMID- 24330620
TI  - Metabarcoding avian diets at airports: implications for birdstrike hazard
      management planning.
AB  - BACKGROUND: Wildlife collisions with aircraft cost the airline industry billions
      of dollars per annum and represent a public safety risk. Clearly, adapting
      aerodrome habitats to become less attractive to hazardous wildlife will reduce
      the incidence of collisions. Formulating effective habitat management strategies
      relies on accurate species identification of high-risk species. This can be
      successfully achieved for all strikes either through morphology and/or DNA-based
      identifications. Beyond species identification, dietary analysis of birdstrike
      gut contents can provide valuable intelligence for airport hazard management
      practices in regards to what food is attracting which species to aerodromes.
      Here, we present birdstrike identification and dietary data from Perth Airport,
      Western Australia, an aerodrome that saw approximately 140,000 aircraft movements
      in 2012. Next-generation high throughput DNA sequencing was employed to
      investigate 77 carcasses from 16 bird species collected over a 12-month period.
      Five DNA markers, which broadly characterize vertebrates, invertebrates and
      plants, were used to target three animal mitochondrial genes (12S rRNA, 16S rRNA,
      and COI) and a plastid gene (trnL) from DNA extracted from birdstrike carcass
      gastrointestinal tracts. RESULTS: Over 151,000 DNA sequences were generated,
      filtered and analyzed by a fusion-tag amplicon sequencing approach. Across the 77
      carcasses, the most commonly identified vertebrate was Mus musculus (house
      mouse). Acrididae (grasshoppers) was the most common invertebrate family
      identified, and Poaceae (grasses) the most commonly identified plant family. The
      DNA-based dietary data has the potential to provide some key insights into
      feeding ecologies within and around the aerodrome. CONCLUSIONS: The data
      generated here, together with the methodological approach, will greatly assist in
      the development of hazard management plans and, in combination with existing
      observational studies, provide an improved way to monitor the effectiveness of
      mitigation strategies (for example, netting of water, grass type, insecticides
      and so on) at aerodromes. It is hoped that with the insights provided by dietary
      data, airports will be able to allocate financial resources to the areas that
      will achieve the best outcomes for birdstrike reduction.

PMID- 24330619
TI  - Consumption of cranberry polyphenols enhances human gammadelta-T cell
      proliferation and reduces the number of symptoms associated with colds and
      influenza: a randomized, placebo-controlled intervention study.
AB  - BACKGROUND: Our main objective was to evaluate the ability of cranberry
      phytochemicals to modify immunity, specifically gammadelta-T cell proliferation,
      after daily consumption of a cranberry beverage, and its effect on health
      outcomes related to cold and influenza symptoms. METHODS: The study was a
      randomized, double-blind, placebo-controlled, parallel intervention. Subjects
      drank a low calorie cranberry beverage (450 ml) made with a juice-derived,
      powdered cranberry fraction (n = 22) or a placebo beverage (n = 23), daily, for
      10 wk. PBMC were cultured for six days with autologous serum and PHA-L
      stimulation. Cold and influenza symptoms were self-reported. RESULTS: The
      proliferation index of gammadelta-T cells in culture was almost five times higher
      after 10 wk of cranberry beverage consumption (p <0.001). In the cranberry
      beverage group, the incidence of illness was not reduced, however significantly
      fewer symptoms of illness were reported (p = 0.031). CONCLUSIONS: Consumption of
      the cranberry beverage modified the ex vivo proliferation of gammadelta-T cells.
      As these cells are located in the epithelium and serve as a first line of
      defense, improving their function may be related to reducing the number of
      symptoms associated with a cold and flu.

PMID- 24330621
TI  - High-level diterpene production by transient expression in Nicotiana benthamiana.
AB  - BACKGROUND: Characterization of plant terpene synthases is typically done by
      production of recombinant enzymes in Escherichia coli. This is often difficult
      due to solubility and codon usage issues. Furthermore, plant terpene synthases
      which are targeted to the plastids, such as diterpene synthases, have to be
      shortened in a more or less empirical approach to improve expression. We report
      here an optimized Agrobacterium-mediated transient expression assay in Nicotiana
      benthamiana for plant diterpene synthase expression and product analysis.
      RESULTS: Agrobacterium-mediated transient expression of plant diterpene synthases
      in N. benthamiana led to the accumulation of diterpenes within 3 days of
      infiltration and with a maximum at 5 days. Over 50% of the products were exported
      onto the leaf surface, thus considerably facilitating the analysis by reducing
      the complexity of the extracts. The robustness of the method was tested by
      expressing three different plant enzymes, cembratrien-ol synthase from Nicotiana
      sylvestris, casbene synthase from Ricinus communis and levopimaradiene synthase
      from Gingko biloba. Furthermore, co-expression of a 1-deoxy-D-xylulose-5
      phosphate synthase from tomato and a geranylgeranyl diphosphate synthase from
      tobacco led to a 3.5-fold increase in the amount of cembratrien-ol produced, with
      maximum yields reaching 2500 ng/cm2. CONCLUSION: With this optimized method for
      diterpene synthase expression and product analysis, a single infiltrated leaf of
      N. benthamiana would be sufficient to produce quantities required for the
      structure elucidation of unknown diterpenes. The method will also be of general
      use for gene function discovery, pathway reconstitution and metabolic engineering
      of diterpenoid biosynthesis in plants.

PMID- 24330622
TI  - Training-related changes in early visual processing of functionally illiterate
      adults: evidence from event-related brain potentials.
AB  - BACKGROUND: Event-related brain potentials (ERPs) were used to investigate
      training-related changes in fast visual word recognition of functionally
      illiterate adults. Analyses focused on the left-lateralized occipito-temporal
      N170, which represents the earliest processing of visual word forms. Event
      related brain potentials were recorded from 20 functional illiterates receiving
      intensive literacy training for adults, 10 functional illiterates not
      participating in the training and 14 regular readers while they read words,
      pseudowords or viewed symbol strings. Subjects were required to press a button
      whenever a stimulus was immediately repeated. RESULTS: Attending intensive
      literacy training was associated with improvements in reading and writing skills
      and with an increase of the word-related N170 amplitude. For untrained functional
      illiterates and regular readers no changes in literacy skills or N170 amplitude
      were observed. CONCLUSIONS: Results of the present study suggest that the word
      related N170 can still be modulated in adulthood as a result of the improvements
      in literacy skills.

PMID- 24330623
TI  - Plasma levels of the MMP-9:TIMP-1 complex as prognostic biomarker in breast
      cancer: a retrospective study.
AB  - BACKGROUND: Worldwide more than one million women are annually diagnosed with
      breast cancer. A considerable fraction of these women receive systemic adjuvant
      therapy; however, some are cured by primary surgery and radiotherapy alone.
      Prognostic biomarkers guide stratification of patients into different risk groups
      and hence improve management of breast cancer patients. Plasma levels of Matrix
      Metalloproteinase-9 (MMP-9) and its natural inhibitor Tissue inhibitor of
      metalloproteinase-1 (TIMP-1) have previously been associated with poor patient
      outcome and resistance to certain forms of chemotherapy. To pursue additional
      prognostic information from MMP-9 and TIMP-1, the level of the MMP-9 and TIMP-1
      complex (MMP-9:TIMP-1) was investigated in plasma from breast cancer patients.
      METHODS: Detection of protein:protein complexes in plasma was performed using a
      commercially available ELISA kit and, for the first time, the highly sensitive in
      solution proximity ligation assay (PLA). We screened plasma from 465 patients
      with primary breast cancer for prognostic value of the MMP-9:TIMP-1 complex. Both
      assays were validated and applied for quantification of MMP-9:TIMP-1
      concentration. In this retrospective study, we analyzed the association between
      the concentration of the MMP-9:TIMP-1 complex and clinicopathological data and
      disease free survival (DFS) in univariate and multivariate survival analyses.
      RESULTS: Following successful validation both assays were applied for MMP-9:TIMP
      1 measurements. Of the clinicopathological parameters, only menopausal status
      demonstrated significant association with the MMP-9:TIMP-1 complex; P = 0.03 and
      P = 0.028 for the ELISA and PLA measurements, respectively. We found no
      correlation between the MMP-9:TIMP-1 protein complex and DFS neither in
      univariate nor in multivariate survival analyses. CONCLUSIONS: Despite earlier
      reports linking MMP-9 and TIMP-1 with prognosis in breast cancer patients, we
      here demonstrate that plasma levels of the MMP-9:TIMP-1 protein complex hold no
      prognostic information in primary breast cancer as a stand-alone marker. We
      demonstrate that the highly sensitive in-solution PLA can be employed for
      measurements of protein:protein complexes in plasma.

PMID- 24330624
TI  - A deep insight into the sialotranscriptome of the mosquito, Psorophora albipes.
AB  - BACKGROUND: Psorophora mosquitoes are exclusively found in the Americas and have
      been associated with transmission of encephalitis and West Nile fever viruses,
      among other arboviruses. Mosquito salivary glands represent the final route of
      differentiation and transmission of many parasites. They also secrete molecules
      with powerful pharmacologic actions that modulate host hemostasis, inflammation,
      and immune response. Here, we employed next generation sequencing and proteome
      approaches to investigate for the first time the salivary composition of a
      mosquito member of the Psorophora genus. We additionally discuss the evolutionary
      position of this mosquito genus into the Culicidae family by comparing the
      identity of its secreted salivary compounds to other mosquito salivary proteins
      identified so far. RESULTS: Illumina sequencing resulted in 13,535,229 sequence
      reads, which were assembled into 3,247 contigs. All families were classified
      according to their in silico-predicted function/ activity. Annotation of these
      sequences allowed classification of their products into 83 salivary protein
      families, twenty (24.39%) of which were confirmed by our subsequent proteome
      analysis. Two protein families were deorphanized from Aedes and one from
      Ochlerotatus, while four protein families were described as novel to Psorophora
      genus because they had no match with any other known mosquito salivary sequence.
      Several protein families described as exclusive to Culicines were present in
      Psorophora mosquitoes, while we did not identify any member of the protein
      families already known as unique to Anophelines. Also, the Psorophora salivary
      proteins had better identity to homologs in Aedes (69.23%), followed by
      Ochlerotatus (8.15%), Culex (6.52%), and Anopheles (4.66%), respectively.
      CONCLUSIONS: This is the first sialome (from the Greek sialo = saliva) catalog of
      salivary proteins from a Psorophora mosquito, which may be useful for better
      understanding the lifecycle of this mosquito and the role of its salivary
      secretion in arboviral transmission.

PMID- 24330625
TI  - Chromophobe renal cell carcinoma with concomitant sarcomatoid transformation and
      osseous metaplasia: a case report.
AB  - BACKGROUND: Chromophobe renal cell carcinoma is the third most common form of
      adult renal epithelial neoplasm. A sarcomatoid component occurs in approximately
      8% of all chromophobe renal cell carcinoma cases, while metaplastic bone
      formation is extremely rare. CASE PRESENTATION: An abdominal computed tomography
      scan revealed a hypovascular tumor with focal calcification, measuring 2.5 * 2.3
      cm, in the upper pole of the right kidney. The tumor was clinically diagnosed as
      a right renal cell carcinoma that showed signs of calcification, and a
      laparoscopic right radical nephrectomy was performed. The cut surface of the
      tumor was beige in color and indicated that the tumor was an extensively ossified
      mass. Histological analysis revealed three distinct morphological components of
      the tumor. The chromophobe renal cell carcinoma consisted of compact epithelial
      cells arranged in a nested pattern, and these were mixed with extensive areas of
      sarcomatoid spindle cells with marked nuclear pleomorphism and brisk mitotic
      activity. The tumor also contained multiple foci of metaplastic ossification.
      CONCLUSION: Chromophobe renal cell carcinoma with concomitant osseous metaplasia
      and sarcomatoid transformation is a very rare occurrence.

PMID- 24330627
TI  - Prolongation of life by adoptive cell therapy with cascade primed immune cells in
      four patients with non-small cell lung cancer stages IIIB and IV and a pancoast
      tumor: a case series.
AB  - INTRODUCTION: Despite newer treatment modalities, few patients with non-small
      cell lung cancer in stages IIIB and IV survive the median of one year. We present
      four patients with non-small cell lung cancer treated with an adjuvant therapy
      with cascade primed immune cells. The in vitro stimulated expression of cancer
      information on the patients' monocytes matures and activates T lymphocytes to
      destroy cancer cells. The cascade primed immune cell therapy significantly
      improved the quality of life and the lifespan of all four patients; thus far,
      three patients survived 40, 55 and 120 months, respectively; and one patient died
      39 months after diagnosis. CASE PRESENTATION: Patient 1, stage IV (T4N2M1): The
      adenocarcinoma of the 67-year-old German Caucasian man infiltrated into the
      mediastinal lymph nodes and iliosacral bones. Chemotherapy modalities were
      started immediately after diagnosis of cancer, and cascade primed immune cell
      therapy one year later. The patient survived 39 months.Patient 2, stage IV
      (T3N3M1a): The 62-year-old German Caucasian woman presented with adenocarcinoma
      of the lower lobe with infiltrated lymph nodes of the mediastinum and malignant
      pleural effusion. Chemotherapy, radiation and the cascade primed immune cell
      therapy were administered together. The patient is still alive after 40
      months.Patient 3, stage IIIB (T4N1-2M0): The 75-year-old German Caucasian woman
      presented with an undifferentiated tumor and a separate tumor nodule in the
      ipsilateral lobe. The patient received only cascade primed immune cell therapy
      after tumor resection and has survived for the last 55 months.Patient 4, pancoast
      tumor (IIIB, T3N3M0): The 77-year-old German Caucasian man presented with an
      undifferentiated tumor that infiltrated the lymph nodes, the clavicle, one rib
      and the plexus brachialis. In addition to chemotherapy and radiation, cascade
      primed immune cells were administered every weekday for one year. After four
      months, no living tumor cell was detected in the resected lung, the lymph nodes
      or the bone material. The patient is still alive after 120 months. CONCLUSIONS:
      The novel adoptive cell therapy with cascade primed immune cells significantly
      increased the survival rate and maintained the quality of life for four patients
      with non-small cell lung cancer in stages IIIB and IV. Our findings indicate that
      tumor resection, chemotherapy and radiation appear to support the cascade primed
      immune cell therapy.

PMID- 24330626
TI  - Screen-based media use clusters are related to other activity behaviours and
      health indicators in adolescents.
AB  - BACKGROUND: Screen-based media (SBM) occupy a considerable portion of young
      peoples' discretionary leisure time. The aim of this paper was to investigate
      whether distinct clusters of SBM use exist, and if so, to examine the
      relationship of any identified clusters with other activity/sedentary behaviours
      and physical and mental health indicators. METHODS: The data for this study come
      from 643 adolescents, aged 14 years, who were participating in the longitudinal
      Western Australian Pregnancy Cohort (Raine) Study through May 2003 to June 2006.
      Time spent on SBM, phone use and reading was assessed using the Multimedia
      Activity Recall for Children and Adults. Height, weight, muscle strength were
      measured at a clinic visit and the adolescents also completed questionnaires on
      their physical activity and psychosocial health. Latent class analysis (LCA) was
      used to analyse groupings of SBM use. RESULTS: Three clusters of SBM use were
      found; C1 'instrumental computer users' (high email use, general computer use),
      C2 'multi-modal e-gamers' (both high console and computer game use) and C3
      'computer e-gamers' (high computer game use only). Television viewing was
      moderately high amongst all the clusters. C2 males took fewer steps than their
      male peers in C1 and C3 (-13,787/week, 95% CI: -4619 to -22957, p = 0.003 and 
      14,806, 95% CI: -5,306 to -24,305, p = 0.002) and recorded less MVPA than the C1
      males (-3.5 h, 95% CI: -1.0 to -5.9, p = 0.005). There was no difference in
      activity levels between females in clusters C1 and C3. CONCLUSION: SBM use by
      adolescents did cluster and these clusters related differently to
      activity/sedentary behaviours and both physical and psychosocial health
      indicators. It is clear that SBM use is not a single construct and future
      research needs to take consideration of this if it intends to understand the
      impact SBM has on health.

PMID- 24330628
TI  - Frameworks for evaluating health research capacity strengthening: a qualitative
      study.
AB  - BACKGROUND: Health research capacity strengthening (RCS) projects are often
      complex and hard to evaluate. In order to inform health RCS evaluation efforts,
      we aimed to describe and compare key characteristics of existing health RCS
      evaluation frameworks: their process of development, purpose, target users,
      structure, content and coverage of important evaluation issues. A secondary
      objective was to explore what use had been made of the ESSENCE framework, which
      attempts to address one such issue: harmonising the evaluation requirements of
      different funders. METHODS: We identified and analysed health RCS evaluation
      frameworks published by seven funding agencies between 2004 and 2012, using a
      mixed methods approach involving structured qualitative analyses of documents, a
      stakeholder survey and consultations with key contacts in health RCS funding
      agencies. RESULTS: The frameworks were intended for use predominantly by the
      organisations themselves, and most were oriented primarily towards funders'
      internal organisational performance requirements. The frameworks made limited
      reference to theories that specifically concern RCS. Generic devices, such as
      logical frameworks, were typically used to document activities, outputs and
      outcomes, but with little emphasis on exploring underlying assumptions or
      contextual constraints. Usage of the ESSENCE framework appeared limited.
      CONCLUSIONS: We believe that there is scope for improving frameworks through the
      incorporation of more accessible information about how to do evaluation in
      practice; greater involvement of stakeholders, following evaluation capacity
      building principles; greater emphasis on explaining underlying rationales of
      frameworks; and structuring frameworks so that they separate generic and project
      specific aspects of health RCS evaluation. The third and fourth of these
      improvements might assist harmonisation.

PMID- 24330629
TI  - Relative expression of proprotein convertases in rat ovaries during pregnancy.
AB  - BACKGROUND: Proprotein convertases are a family of serine proteinases that are
      related to bacterial subtilisin and yeast kexin. They are involved in
      posttranslational processing of the precursors of a vast number of cellular
      proteins. With the exception of PC1/3, the relative expression levels of the
      proprotein convertases in the ovary during pregnancy have not been reported. The
      purpose of this study is to determine by real-time PCR the relative expression
      levels of all nine proprotein convertases in rat ovaries during pregnancy and at
      3 days postpartum. METHODS: RNA was extracted from ovaries at Day 0, 4, 9, 11,
      13, 15, 18, and 20 of pregnancy as well as 3 days postpartum. Relative expression
      levels of Pcsk1, Pcsk2, Furin, Pcsk4, Pcsk5, Pcsk6, Pcsk7, Mbtps1 and Pcsk9 were
      determined with real-time PCR. Results were reported as fold-change over the
      level at Day 0 of pregnancy. RESULTS: Results showed that Pcsk1 and Pcsk6 were
      upregulated as gestation advanced, in parallel with an observed increase in
      relaxin transcript. Pcsk2 showed downregulation as gestation advanced, while
      Pcsk5 showed relatively higher levels in early pregnancy and postpartum, but
      lower level in mid-pregnancy. On the other hand, Furin, Pcsk4, Pcsk7, Mbtps1 and
      Pcsk9 showed little change of expression throughout gestation. CONCLUSION: PC1/3
      (PCSK1) and PACE4 (PCSK6) may play an important role in proprotein processing in
      the ovary during late pregnancy.

PMID- 24330630
TI  - Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib
      dosing regimen in the dog.
AB  - BACKGROUND: Cimicoxib is a new coxib anti-inflammatory drug for use in the dog.
      To determine a preclinical dosage regimen for cimicoxib in dog, a reversible
      model of kaolin-induced paw inflammation was used. Dosage regimens were
      established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach
      (indirect response model). RESULTS: Analgesic, anti-inflammatory and antipyretic
      endpoints investigated with the inflammation model established the efficacy of
      cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle
      dogs.For both the oral and IV route of administration two groups of dogs to be
      identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The
      terminal half-life after oral administration was 8.0 +/- 0.6 h for the PM and 4.6
      +/- 2.6 h for the EM groups, with the corresponding values after the IV route
      being 5.6 +/- 1.7 h and 2.7 +/- 0.9 h (mean +/- SD).The main pharmacodynamic
      parameters (potency, efficacy, and sensitivity) were estimated for four endpoints
      (body temperature, creeping speed, ground vertical reaction force and clinical
      lameness score). The plasma concentration corresponding to half the maximum of
      the indirect effect were 239 MUg/L for creeping speed, 284 MUg/L for the lameness
      score, 161 MUg/L for the ground reaction vertical force and 193 MUg/L for the
      body temperature.To document possible polymorphism of the cimicoxib disposition
      in the target dog population, cimicoxib was administered by the intravenous route
      to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40
      dogs were of same order of the magnitude as those of the EM beagle dogs. Thus
      pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs
      were selected to simulate the dose-effect relationship of cimicoxib after an oral
      administration allowing a dosage regimen to be selected for confirmation by a
      clinical trial. CONCLUSIONS: Cimicoxib was an efficacious anti-inflammatory,
      antipyretic and analgesic drug and a dosage regimen of 2 mg/kg daily was
      determined for confirmatory clinical trials.

PMID- 24330632
TI  - Evaluation of mechanical properties of three different screws for rapid maxillary
      expansion.
AB  - BACKGROUND: The aim of this in vitro study was the evaluation of the mechanical
      properties the screws for rapid maxillary expansion (RME). METHODS: Three
      commercially available screws for RME were tested: Leone A2620; Dentaurum Hyrax;
      Forestadent Palatal Split Screw. All expansion screws were 10 mm in size. For the
      evaluation of mechanical properties, the screws for RME were adjusted using the
      same maxillary dental model. An Instron 3365 testing machine with a load cell of
      5 kN recorded the forces released by the screws at different amounts of
      activation (1, 5, 10, 15 and 20 quarters of a turn). Each type of screw was
      tested 10 times. Comparisons between the forces released by the different types
      of screws at different amounts of activation were carried out by means of
      analysis of Kruskal-Wallis test with post-hoc test di Tukey (P < 0.05). RESULTS:
      The results of this study showed that all 3 expansion devices were able to
      develop forces that could produce a separation of the palatine processes. The
      Hyrax and A2620 expanders developed force values over 20 kg and the Palatal Split
      screws about 16 kg. Both the A2620 and Hyrax expanders showed significantly
      greater amounts of forces at all the different amounts of activations with
      respect to the Palatal Split screw. CONCLUSIONS: All tested devices showed the
      capability of developing expansion forces (16-20 kg) adequate for RME. The A2620
      and Hyrax expanders showed a greater level of rigidity than the Palatal Split
      screw.

PMID- 24330631
TI  - Molecular epidemiology of the emerging zoonosis agent Anaplasma phagocytophilum
      (Foggie, 1949) in dogs and ixodid ticks in Brazil.
AB  - BACKGROUND: Anaplasma phagocytophilum is an emerging pathogen of humans, dogs and
      other animals, and it is transmitted by ixodid ticks. The objective of the
      current study was a) detect A. phagocytophilum in dogs and ixodid ticks using
      real-time Polymerase Chain Reaction (qPCR); and b) Determine important variables
      associated to host, environment and potential tick vectors that are related to
      the presence of A. phagocytophilum in dogs domiciled in Rio de Janeiro, Brazil.
      METHODS: We tested blood samples from 398 dogs and samples from 235 ticks,
      including 194 Rhipicephalus sanguineus sensu lato, 15 Amblyomma cajennense, 8
      Amblyomma ovale and 18 pools of Amblyomma sp. nymphs. A semi-structured
      questionnaire was applied by interviewing each dog owner. Deoxyribonucleic acid
      obtained from ticks and dog buffy coat samples were amplified by qPCR (msp2
      gene). The sequencing of 16S rRNA and groESL heat shock operon genes and a
      phylogenetic analysis was performed. The multiple logistic regression model was
      created as a function of testing positive dogs for A. phagocytophilum. RESULTS:
      Among the 398 blood samples from dogs, 6.03% were positive for A.
      phagocytophilum. Anaplasma phagocytophilum was detected in one A. cajennense
      female tick and in five R. sanguineus sensu lato ticks (four males and one
      female). The partial sequences of the 16S rRNA, and groESL genes obtained were
      highly similar to strains of A. phagocytophilum isolated from wild birds from
      Brazil and human pathogenic strains. The tick species collected in positive dogs
      were R. sanguineus sensu lato and A. cajennense, with A.cajennense being
      predominant. Tick infestation history (OR = 2.86, CI = 1.98-14.87), dog size (OR
      = 2.41, IC: 1.51-12.67), the access to forest areas (OR = 3:51, CI: 1.52-16.32),
      hygiene conditions of the environment in which the dogs lived (OR = 4.35, CI:
      1.86-18.63) and Amblyomma sp. infestation (OR = 6.12; CI: 2.11-28.15) were
      associated with A. phagocytophilum infection in dogs. CONCLUSIONS: This is the
      first report of A. phagocytophilum in ixodid ticks from Brazil. The detection of
      A. phagocitophylum in A. cajennense, an aggressive feeder on a wide variety of
      hosts, including humans, is considered a public health concern.

PMID- 24330633
TI  - Choroid metastases revealing primary clear cell adenocarcinoma of the lung
      effectively treated with cisplatin and pemetrexed: a case report.
AB  - INTRODUCTION: The aim of the present report was to draw the attention of
      oncologists to the importance of prompt diagnosis of primary clear cell
      adenocarcinoma of the lung, which allows early initiation of treatment to
      maintain quality of life. CASE PRESENTATION: A 63-year-old Chinese woman
      initially presented to our facility with multifocal bilateral choroid metastatic
      lesions that were found to originate from a primary clear cell adenocarcinoma of
      the lung (T2bN2M1b, stage IV). A thorough ophthalmologic evaluation, study of our
      patient's history, imaging studies and comprehensive immunohistochemical staining
      tests led to the diagnosis of this rare lung tumor. CONCLUSIONS: Although this
      uncommon cancer is unfortunately already at a late stage when choroid metastases
      develop, systemic chemotherapy alone is sufficient to preserve vision and gain
      control over the disease.

PMID- 24330634
TI  - Genomic divergence of zebu and taurine cattle identified through high-density SNP
      genotyping.
AB  - BACKGROUND: Natural selection has molded evolution across all taxa. At an
      arguable date of around 330,000 years ago there were already at least two
      different types of cattle that became ancestors of nearly all modern cattle, the
      Bos taurus taurus more adapted to temperate climates and the tropically adapted
      Bos taurus indicus. After domestication, human selection exponentially
      intensified these differences. To better understand the genetic differences
      between these subspecies and detect genomic regions potentially under divergent
      selection, animals from the International Bovine HapMap Experiment were genotyped
      for over 770,000 SNP across the genome and compared using smoothed F(ST). The
      taurine sample was represented by ten breeds and the contrasting zebu cohort by
      three breeds. RESULTS: Each cattle group evidenced similar numbers of polymorphic
      markers well distributed across the genome. Principal components analyses and
      unsupervised clustering confirmed the well-characterized main division of
      domestic cattle. The top 1% smoothed F(ST), potentially associated to positive
      selection, contained 48 genomic regions across 17 chromosomes. Nearly half of the
      top F(ST) signals (n = 22) were previously detected using a lower density SNP
      assay. Amongst the strongest signals were the BTA7:~50 Mb and BTA14:~25 Mb; both
      regions harboring candidate genes and different patterns of linkage
      disequilibrium that potentially represent intrinsic differences between cattle
      types. The bottom 1% of the smoothed F(ST) values, potentially associated to
      balancing selection, included 24 regions across 13 chromosomes. These regions
      often overlap with copy number variants, including the highly variable region at
      BTA23:~24 Mb that harbors a large number of MHC genes. Under these regions, 318
      unique Ensembl genes are annotated with a significant overrepresentation of
      immune related pathways. CONCLUSIONS: Genomic regions that are potentially linked
      to purifying or balancing selection processes in domestic cattle were identified.
      These regions are of particular interest to understand the natural and human
      selective pressures to which these subspecies were exposed to and how the genetic
      background of these populations evolved in response to environmental challenges
      and human manipulation.

PMID- 24330635
TI  - Engineering of a green-light inducible gene expression system in Synechocystis
      sp. PCC6803.
AB  - In order to construct a green-light-regulated gene expression system for
      cyanobacteria, we characterized a green-light sensing system derived from
      Synechocystis sp. PCC6803, consisting of the green-light sensing histidine kinase
      CcaS, the cognate response regulator CcaR, and the promoter of cpcG2 (PcpcG 2 ).
      CcaS and CcaR act as a genetic controller and activate gene expression from PcpcG
      2 with green-light illumination. The green-light induction level of the native
      PcpcG 2 was investigated using GFPuv as a reporter gene inserted in a broad-host
      range vector. A clear induction of protein expression from native PcpcG 2 under
      green-light illumination was observed; however, the expression level was very low
      compared with Ptrc , which was reported to act as a constitutive promoter in
      cyanobacteria. Therefore, a Shine-Dalgarno-like sequence derived from the cpcB
      gene was inserted in the 5' untranslated region of the cpcG2 gene, and the
      expression level of CcaR was increased. Thus, constructed engineered green-light
      sensing system resulted in about 40-fold higher protein expression than with the
      wild-type promoter with a high ON/OFF ratio under green-light illumination. The
      engineered green-light gene expression system would be a useful genetic tool for
      controlling gene expression in the emergent cyanobacterial bioprocesses.

PMID- 24330636
TI  - Log-binomial models: exploring failed convergence.
AB  - BACKGROUND: Relative risk is a summary metric that is commonly used in
      epidemiological investigations. Increasingly, epidemiologists are using log
      binomial models to study the impact of a set of predictor variables on a single
      binary outcome, as they naturally offer relative risks. However, standard
      statistical software may report failed convergence when attempting to fit log
      binomial models in certain settings. The methods that have been proposed in the
      literature for dealing with failed convergence use approximate solutions to avoid
      the issue. This research looks directly at the log-likelihood function for the
      simplest log-binomial model where failed convergence has been observed, a model
      with a single linear predictor with three levels. The possible causes of failed
      convergence are explored and potential solutions are presented for some cases.
      RESULTS: Among the principal causes is a failure of the fitting algorithm to
      converge despite the log-likelihood function having a single finite maximum.
      Despite these limitations, log-binomial models are a viable option for
      epidemiologists wishing to describe the relationship between a set of predictors
      and a binary outcome where relative risk is the desired summary measure.
      CONCLUSIONS: Epidemiologists are encouraged to continue to use log-binomial
      models and advocate for improvements to the fitting algorithms to promote the
      widespread use of log-binomial models.

PMID- 24330637
TI  - Effect of bee venom on IL-6, COX-2 and VEGF levels in polycystic ovarian syndrome
      induced in Wistar rats by estradiol valerate.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) is a low-grade inflammatory
      disease characterized by hyperandrogenemia, hirsutism, chronic anovulation and
      vascular disorder. Interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and vascular
      endothelial growth factor (VEGF) are triggered by inflammatory stimuli and lead
      to angiogenesis and pathogenesis of the ovary. Honeybee venom (HBV) contains an
      array of biologically active components possessing various pharmaceutical
      properties. This study was designed to assess the possibility of HBV application
      as an anti-inflammatory therapeutic agent to suppress levels of the main
      inflammatory mediators IL-6, COX-2 and VEGF.To induce PCOS, 1 mg of estradiol
      valerate (EV) per 100 g of body weight was subcutaneously (SC) injected into
      eight-week-old rats. After 60 days, 0.5 mg/kg of HBV was administered
      Intraperitoneal (IP) for 14 consecutive days, and the results of PCOS treatment
      were investigated. Rats were then anesthetized with CO2, and the ovaries were
      surgically removed. Serum IL-6 was detected by the ELISA kit. Immunoexpression of
      COX-2 and VEGF were examined in three groups: EV-induced PCOS, HBV-treated PCOS
      and control animals. RESULTS: Thickness of theca layer, number and diameter of
      cysts and levels of IL-6 significantly decreased in HBV group relative to PCOS
      group. The immunohistochemical analysis showed an increase in COX-2 and VEGF
      expression in PCOS group whereas HBV-treated rats presented weak and irregular
      immunostaining. CONCLUSIONS: Our results suggest that the beneficial effect of
      HBV may be mediated through its inhibitory effect on serum IL-6 level and ovarian
      COX-2 and VEGF expression.

PMID- 24330638
TI  - Motor cortical processing is causally involved in object recognition.
AB  - BACKGROUND: Motor activity during vicarious experience of actions is a widely
      reported and studied phenomenon, and motor system activity also accompanies
      observation of graspable objects in the absence of any actions. Such motor
      activity is thought to reflect simulation of the observed action, or preparation
      to interact with the object, respectively. RESULTS: Here, in an initial
      exploratory study, we ask whether motor activity during observation of object
      directed actions is involved in processes related to recognition of the object
      after initial exposure. Single pulse Transcranial Magnetic Stimulation (TMS) was
      applied over the thumb representation of the motor cortex, or over the vertex,
      during observation of a model thumb typing on a cell-phone, and performance on a
      phone recognition task at the end of the trial was assessed. Disrupting motor
      processing over the thumb representation 100 ms after the onset of the typing
      video impaired the ability to recognize the phone in the recognition test,
      whereas there was no such effect for TMS applied over the vertex and no TMS
      trials. Furthermore, this effect only manifested for videos observed from the
      first person perspective. In an additional control condition, there was no
      evidence for any effects of TMS to the thumb representation or vertex when
      observing and recognizing non-action related shape stimuli. CONCLUSION: Overall,
      these data provide evidence that motor cortical processing during observation of
      object-directed actions from a first person perspective is causally linked to the
      formation of enduring representations of objects-of-action.

PMID- 24330639
TI  - BMP-9 expression in human traumatic heterotopic ossification: a case report.
AB  - BACKGROUND: Heterotopic ossification (HO) is defined as the abnormal formation of
      mature bone in soft tissue, notably skeletal muscle. The morbidity of HO in
      polytraumatized patients impacts the functional outcome, impairs rehabilitation,
      and increases costs due to subsequent surgical interventions. CASE PRESENTATION:
      We present the case of a 34-year-old African male who developed severe HO around
      his right hip 11 days after a major trauma. Immunohistochemical analyses of
      resected tissue revealed that several BMPs were expressed in the HO, including
      highly osteogenic BMP-9. CONCLUSIONS: To the best of our knowledge, this is the
      first report of local BMP expression, notably BMP-9, in traumatic HO, and
      suggests that BMP-9, possibly through mrSCs, can contribute to HO formation in
      soft tissues when a suitable microenvironment is present.

PMID- 24330640
TI  - Inducing articular cartilage phenotype in costochondral cells.
AB  - INTRODUCTION: Costochondral cells may be isolated with minimal donor site
      morbidity and are unaffected by pathologies of the diarthrodial joints.
      Identification of optimal exogenous stimuli will allow abundant and robust
      hyaline articular cartilage to be formed from this cell source. METHODS: In a
      three factor, two level full factorial design, the effects of hydrostatic
      pressure (HP), transforming growth factor beta1 (TGF-beta1), and chondroitinase
      ABC (C-ABC), and all resulting combinations, were assessed in third passage
      expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage
      was assessed for matrix content, superficial zone protein (SZP), and mechanical
      properties. RESULTS: Hyaline articular cartilage was generated, demonstrating the
      presence of type II collagen and SZP, and the absence of type I collagen. TGF
      beta1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by
      75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC
      significantly increased collagen content, and fibril density and diameter,
      leading to a 125% increase in tensile modulus. Hydrostatic pressure increased
      fibril diameter by 30% and tensile modulus by 45%. Combining TGF-beta1 with C-ABC
      synergistically increased collagen content by 300% and tensile strength by 320%,
      over control. No significant differences were observed between C-ABC/TGF-beta1
      dual treatment and HP/C-ABC/TGF-beta1. CONCLUSIONS: Employing biochemical,
      biophysical, and mechanical stimuli generated robust hyaline articular cartilage
      with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650
      kPa. Using expanded, redifferentiated costochondral cells in the self-assembling
      process allows for recapitulation of robust mechanical properties, and induced
      SZP expression, key characteristics of functional articular cartilage.

PMID- 24330641
TI  - Physical activity in daily life is associated with lower adiposity values than
      doing weekly sports in Lc65+ cohort at baseline.
AB  - BACKGROUND: Overweight and obesity prevalence is the highest at age 65-75 years
      in Lausanne (compared with younger classes). We aimed to describe 1) eating
      habits, daily physical activity (PA), and sports frequency in community-dwelling
      adults aged 65-70, 2) the links of these behaviors with socio-economic factors,
      and 3) with adiposity. METHODS: Cross-sectional analysis of Lc65+ cohort at
      baseline, including 1260 adults from the general population of Lausanne aged 65
      70 years. Eating habits (8 items from MNA) and PA (sports frequency and daily PA:
      walking and using stairs) were assessed by questionnaires. Body mass index (BMI),
      supra-iliac (SISF), triceps skin-folds (TSF), waist circumference (WC), and WHR
      were measured. RESULTS: Prevalence of overweight (BMI 25.0-29.9 kg/m2), obesity
      (BMI >= 30.0 kg/m2), and abdominal obesity was 53%, 24%, and 45% in men; 35%,
      23%, and 45% in women.Intake of fruits or vegetables (FV) >= twice/day was
      negatively associated with male sex (prevalence 81% versus 90%, chi-square P <
      0.001). The proportion avoiding stairs in daily life was higher among women (25%)
      than among men (20%, chi-square P=0.003).In multivariate analyses among both
      sexes, eating FV, using stairs in daily life ("stairs"), and doing sports >=
      once/week were significantly negatively associated with financial difficulties
      (stairs: OR=0.54, 95% CI=0.40-0.72) and positively with educational level
      (stairs: OR=1.68, 95% CI=1.17-2.43 for high school).For all five log-transformed
      adiposity indicators in women, and for all indicators except SISF and TSF in men,
      a gradual decrease in adiposity was observed from category "no stairs, sports <
      once/week" (reference), to "no stairs, sports >= once/week", to "stairs, sports <
      once/week", and "stairs, sports >= once/week" (for example: WC in men,
      respectively: beta= -0.03, 95% CI= -0.07-0.02; beta= -0.06, 95% CI= -0.09- -0.03;
      beta= -0.10, 95% CI= -0.12- -0.07). CONCLUSIONS: In this population with high
      overweight and obesity prevalence, eating FV and PA were strongly negatively
      associated with financial difficulties and positively with education. Using
      stairs in daily life was more strongly negatively associated with adiposity than
      doing sports >= once/week.

PMID- 24330642
TI  - Inference of mechanical states of intestinal motor activity using hidden Markov
      models.
AB  - BACKGROUND: Contractions and relaxations of the muscle layers within the
      digestive tract alter the external diameter and the internal pressures. These
      changes in diameter and pressure move digesting food and waste products. Defining
      these complex relationships is a fundamental step for neurogastroenterologists to
      be able define normal and abnormal gut motility. RESULTS: Utilising an in vitro
      technique that allows for the simultaneous recording of intraluminal pressure
      (manometry) and gut diameter (video) in an isolated section of rabbit colon, we
      developed a technique to help define the mechanical states of the muscle at any
      point in space and time during actual peristaltic movements. This was achieved by
      directly relating the changes in pressure to the changes in diameter along the
      length of the gut studied. For each individual measure of pressure or diameter, 3
      dynamic state components were identified; increasing or decreasing changes or a
      stable period. Two additional static state components, fully contracted and fully
      distended, were defined for the diameter. Then qualitative mechanical states of
      the muscle activity were defined as combinations of these state components. A
      hidden Markov model was used to correlate adjacent-in-time samples, and the
      Viterbi algorithm was used to infer the most likely sequence of mechanical states
      based on the observed data. From this a spatiotemporal map of the mechanical
      states was produced, showing the regions of active contractions, active
      relaxations, or passive states along the length of the gut throughout the entire
      recording period. CONCLUSIONS: The identification of mechanical muscles states
      based on gut diameter and intraluminal pressure was possible by modelling muscle
      activation with a hidden Markov model.

PMID- 24330643
TI  - Automatic detection of anomalies in screening mammograms.
AB  - BACKGROUND: Diagnostic performance in breast screening programs may be influenced
      by the prior probability of disease. Since breast cancer incidence is roughly
      half a percent in the general population there is a large probability that the
      screening exam will be normal. That factor may contribute to false negatives.
      Screening programs typically exhibit about 83% sensitivity and 91% specificity.
      This investigation was undertaken to determine if a system could be developed to
      pre-sort screening-images into normal and suspicious bins based on their
      likelihood to contain disease. Wavelets were investigated as a method to parse
      the image data, potentially removing confounding information. The development of
      a classification system based on features extracted from wavelet transformed
      mammograms is reported. METHODS: In the multi-step procedure images were
      processed using 2D discrete wavelet transforms to create a set of maps at
      different size scales. Next, statistical features were computed from each map,
      and a subset of these features was the input for a concerted-effort set of naive
      Bayesian classifiers. The classifier network was constructed to calculate the
      probability that the parent mammography image contained an abnormality. The
      abnormalities were not identified, nor were they regionalized.The algorithm was
      tested on two publicly available databases: the Digital Database for Screening
      Mammography (DDSM) and the Mammographic Images Analysis Society's database
      (MIAS). These databases contain radiologist-verified images and feature common
      abnormalities including: spiculations, masses, geometric deformations and fibroid
      tissues. RESULTS: The classifier-network designs tested achieved sensitivities
      and specificities sufficient to be potentially useful in a clinical setting. This
      first series of tests identified networks with 100% sensitivity and up to 79%
      specificity for abnormalities. This performance significantly exceeds the mean
      sensitivity reported in literature for the unaided human expert. CONCLUSIONS:
      Classifiers based on wavelet-derived features proved to be highly sensitive to a
      range of pathologies, as a result Type II errors were nearly eliminated. Pre
      sorting the images changed the prior probability in the sorted database from 37%
      to 74%.

PMID- 24330644
TI  - Isolation and Complete Genome Sequencing of Bluetongue Virus Serotype 12 from
      India.
AB  - Bluetongue virus (BTV) causes disease mainly in sheep, but can be transmitted via
      other domestic and wild ruminants, resulting in pecuniary burden and trade
      restrictions. Segmented genome with the possibility of reassortment, existence of
      26 serotypes, geographical restriction in the distribution of many of the
      serotypes, use of live attenuated vaccines and the lack of complete sequences of
      viruses isolated from several parts of the globe have complicated our
      understanding of the origin, movement and distribution of BTV. Recent efforts in
      genome sequencing of several strains have helped in better comprehending BTV
      epidemiology. In an effort to contribute to the genetic epidemiology of BTV in
      India, we report the isolation and complete genome sequencing of a BTV serotype
      12 virus (designated NMO1). This is the first BTV-12 isolated from India and the
      second BTV-12 to be sequenced worldwide. The analysis of sequences of this virus
      suggests that NMO1 derived its segments from viruses belonging to western
      topotype viruses, as well as those from South-East Asia and India. The results
      have implications for understanding the origin, emergence/re-emergence and
      movement of BTV as well as for the development of vaccines and diagnostics based
      on robust epidemiological data.

PMID- 24330646
TI  - The expression and role of serotonin receptor 5HTR2A in canine osteoblasts and an
      osteosarcoma cell line.
AB  - BACKGROUND: The significance of the serotonergic system in bone physiology and,
      more specifically, the importance of the five hydroxytryptamine receptor 2A
      (5HTR2A) in normal osteoblast proliferation have been previously described;
      however the role of serotonin in osteosarcoma remains unclear. Particularly, the
      expression and function of 5HTR2A in canine osteosarcoma has not yet been
      studied, thus we sought to determine if this indoleamine modulates cellular
      proliferation in vitro. Using real time quantitative reverse transcription PCR
      and immunoblot analyses, we explored receptor expression and signaling
      differences between non-neoplastic canine osteoblasts (CnOb) and an osteosarcoma
      cell line (COS). To elucidate specific serotonergic signaling pathways triggered
      by 5HTR2A, we performed immunoblots for ERK and CREB. Finally, we compared cell
      viability and the induction of apoptosis in the presence 5HTR2A agonists and
      antagonists. RESULTS: 5HTR2A was overexpressed in the malignant cell line in
      comparison to normal cells. In CnOb cells, ERK phosphorylation (ERK-P) decreased
      in response to both serotonin and a specific 5HTR2A antagonist, ritanserin. In
      contrast, ERK-P abundance increased in COS cells following either treatment.
      While endogenous CREB was undetectable in CnOb, CREB was observed constitutively
      in COS, with expression and exhibited increased CREB phosphorylation following
      escalating concentrations of ritanserin. To determine the influence of 5HTR2A
      signaling on cell viability we challenged cells with ritanserin and serotonin.
      Our findings confirmed that serotonin treatment promoted cell viability in
      malignant cells but not in normal osteoblasts. Conversely, ritanserin reduced
      cell viability in both the normal and osteosarcoma cells. Further, ritanserin
      induced apoptosis in COS at the same concentrations associated with decreased
      cell viability. CONCLUSIONS: These findings confirm the existence of a functional
      5HTR2A in a canine osteosarcoma cell line. Results indicate that intracellular
      second messenger signal coupling of 5HTR2A is different between normal and
      malignant cells, warranting further research to investigate its potential as a
      novel therapeutic target for canine osteosarcoma.

PMID- 24330647
TI  - Genome anatomy of the gastrointestinal pathogen, Vibrio parahaemolyticus of
      crustacean origin.
AB  - Vibrio parahaemolyticus, an important human pathogen, is associated with
      gastroenteritis and transmitted through partially cooked seafood. It has become a
      major concern in the production and trade of marine food products. The prevalence
      of potentially virulent and pathogenic V. parahaemolyticus in raw seafood is of
      public health significance. Here we describe the genome sequence of a V.
      parahaemolyticus isolate of crustacean origin which was cultured from prawns in
      2008 in Selangor, Malaysia (isolate PCV08-7). The next generation sequencing and
      analysis revealed that the genome of isolate PCV08-7 has closest similarity to
      that of V. parahaemolyticus RIMD2210633. However, there are certain unique
      features of the PCV08-7 genome such as the absence of TDH-related hemolysin
      (TRH), and the presence of HU-alpha insertion. The genome of isolate PCV08-7
      encodes a thermostable direct hemolysin (TDH), an important virulence factor that
      classifies PCV08-7 isolate to be a serovariant of O3:K6 strain. Apart from these,
      we observed that there is certain pattern of genetic rearrangements that makes V.
      parahaemolyticus PCV08-7 a non-pandemic clone. We present detailed genome
      statistics and important genetic features of this bacterium and discuss how its
      survival, adaptation and virulence in marine and terrestrial hosts can be
      understood through the genomic blueprint and that the availability of genome
      sequence entailing this important Malaysian isolate would likely enhance our
      understanding of the epidemiology, evolution and transmission of foodborne
      Vibrios in Malaysia and elsewhere. 

PMID- 24330648
TI  - Flow-dependent thrombin and fibrin generation in vitro: opportunities for
      standardization: communication from SSC of the ISTH.

PMID- 24330649
TI  - Unraveling the genetic architecture of subtropical maize (Zea mays L.) lines to
      assess their utility in breeding programs.
AB  - BACKGROUND: Maize is an increasingly important food crop in southeast Asia. The
      elucidation of its genetic architecture, accomplished by exploring quantitative
      trait loci and useful alleles in various lines across numerous breeding programs,
      is therefore of great interest. The present study aimed to characterize
      subtropical maize lines using high-quality SNPs distributed throughout the
      genome. RESULTS: We genotyped a panel of 240 subtropical elite maize inbred lines
      and carried out linkage disequilibrium, genetic diversity, population structure,
      and principal component analyses on the generated SNP data. The mean SNP distance
      across the genome was 70 Kb. The genome had both high and low linkage
      disequilibrium (LD) regions; the latter were dominant in areas near the gene-rich
      telomeric portions where recombination is frequent. A total of 252 haplotype
      blocks, ranging in size from 1 to 15.8 Mb, were identified. Slow LD decay (200
      300 Kb) at r(2) <= 0.1 across all chromosomes explained the selection of
      favorable traits around low LD regions in different breeding programs. The
      association mapping panel was characterized by strong population substructure.
      Genotypes were grouped into three distinct clusters with a mean genetic
      dissimilarity coefficient of 0.36. CONCLUSIONS: The genotyped panel of
      subtropical maize lines characterized in this study should be useful for
      association mapping of agronomically important genes. The dissimilarity uncovered
      among genotypes provides an opportunity to exploit the heterotic potential of
      subtropical elite maize breeding lines.

PMID- 24330650
TI  - A detailed phenotypic analysis of immune cell populations in the bronchoalveolar
      lavage fluid of atopic asthmatics after segmental allergen challenge.
AB  - BACKGROUND: Atopic asthma is characterized by intermittent exacerbations
      triggered by exposure to allergen. Exacerbations are characterized by an acute
      inflammatory reaction in the airways, with recruitment of both innate and
      adaptive immune cells. These cell populations as well as soluble factors are
      critical for initiating and controlling the inflammatory processes in allergic
      asthma. Detailed data on the numbers and types of cells recruited following
      allergen challenge is lacking. In this paper we present an extensive phenotypic
      analysis of the inflammatory cell infiltrate present in the bronchoalveolar
      lavage (BAL) fluid following bronchoscopically directed allergen challenge in
      mild atopic asthmatics. METHODS: A re-analysis of pooled data obtained prior to
      intervention in our randomized, placebo controlled, double blinded study
      (costimulation inhibition in asthma trial [CIA]) was performed. Twenty-four
      subjects underwent bronchoscopically directed segmental allergen challenge
      followed by BAL collection 48 hours later. The BAL fluid was analyzed by multi
      color flow cytometry for immune cell populations and multi-plex ELISA for
      cytokine detection. RESULTS: Allergen instillation induced pro-inflammatory
      cytokines (IL-6) and immune modulating cytokines (IL-2, IFN-?, and IL-10) along
      with an increase in lymphocytes and suppressor cells (Tregs and MDSC).
      Interestingly, membrane expression of CD30 was identified on lymphocytes,
      especially Tregs, but not eosinophils. Soluble CD30 was also detected in the BAL
      fluid after allergen challenge in adult atopic asthmatics. CONCLUSIONS: After
      segmental allergen challenge of adult atopic asthmatics, cell types associated
      with a pro-inflammatory as well as an anti-inflammatory response are detected
      within the BAL fluid of the lung.

PMID- 24330651
TI  - Vernalization treatment induces site-specific DNA hypermethylation at the
      VERNALIZATION-A1 (VRN-A1) locus in hexaploid winter wheat.
AB  - BACKGROUND: Certain temperate species require prolonged exposure to low
      temperature to initiate transition from vegetative growth to flowering, a process
      known as vernalization. In wheat, winter cultivars require vernalization to
      initiate flowering, making vernalization requirement a trait of key importance in
      wheat agronomy. The genetic bases of vernalization response have been largely
      studied in wheat, leading to the characterization of a regulation pathway that
      involves the key gene VERNALIZATION1 (VRN1). While previous studies in wheat and
      barley have revealed the functional role of histone modification in setting VRN1
      expression, other mechanisms might also be involved. Here, we were interested in
      determining whether the cold-induced expression of the wheat VRN-A1 gene is
      associated with a change in DNA methylation. RESULTS: We provide the first DNA
      methylation analysis of the VRN-A1 gene, and describe the existence of
      methylation at CG but also at non CG sites. While CG sites show a bell-shape
      profile typical of gene-body methylation, non CG methylation is restricted to the
      large (8.5 kb) intron 1, in a region harboring fragments of transposable elements
      (TEs). Interestingly, cold induces a site-specific hypermethylation at these non
      CG sites. This increase in DNA methylation is transmitted through mitosis, and is
      reset to its original level after sexual reproduction. CONCLUSIONS: These results
      demonstrate that VRN-A1 has a particular DNA methylation pattern, exhibiting
      rapid shift within the life cycle of a winter wheat plant following exposure to
      particular environmental conditions. The finding that this shift occurs at non CG
      sites in a TE-rich region opens interesting questions onto the possible
      consequences of this type of methylation in gene expression.

PMID- 24330652
TI  - A complicated case of pachydermoperiostosis with spondyloarthritides: a case
      report.
AB  - INTRODUCTION: Pachydermoperiostosis is a rare, hereditary disease commonly
      presenting with digital clubbing, pachydermia and periosteal hypertrophy.
      Therapeutic options for pachydermoperiostosis are few because of the unknown
      pathogenesis. Here, we report the complicated case of a patient with
      pachydermoperiostosis combined with spondyloarthritides, who was refractory to
      steroids and tumor necrosis factor alpha antagonists. We treated this patient
      with zoledronic acid and performed an arthroscopic synovectomy, with a
      satisfactory outcome. To the best of our knowledge, this is the first report in
      English on the combination of zoledronic acid administration and synovectomy for
      the treatment of a patient with pachydermoperiostosis and spondyloarthritides.
      CASE PRESENTATION: An 18-year-old Han Chinese man was diagnosed with
      pachydermoperiostosis in the presence of digital clubbing, periostitis and
      swollen limbs. Combined spondyloarthritides was also considered based on his
      lower back pain, lower limbs synovitis, bilateral sacroiliac sclerosis and a
      positive test for human leukocyte antigen B27, as well as immunoglobulin A
      nephropathy. He was refractory to steroids and tumor necrosis factor alpha
      antagonists, but treated with intravenous zoledronic acid and an arthroscopic
      synovectomy, with a satisfactory outcome. CONCLUSION: This is a rare, complicated
      case of pachydermoperiostosis with spondyloarthritides. Combination therapy of
      zoledronic acid administration with synovectomy is a novel, convenient and
      effective option for patients with pachydermoperiostosis with remarkable
      synovitis.

PMID- 24330654
TI  - Single injection recombinant vesicular stomatitis virus vaccines protect ferrets
      against lethal Nipah virus disease.
AB  - BACKGROUND: Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family
      Paramyxoviridae that is maintained in nature by bats. Outbreaks have occurred in
      Malaysia, Singapore, India, and Bangladesh and have been associated with 40 to
      75% case fatality rates. There are currently no vaccines or postexposure
      treatments licensed for combating human NiV infection. METHODS AND RESULTS: Four
      groups of ferrets received a single vaccination with different recombinant
      vesicular stomatitis virus vectors expressing: Group 1, control with no
      glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment
      protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were
      challenged intranasally with NiV 28 days after vaccination. Control ferrets in
      Group 1 showed characteristic clinical signs of NiV disease including respiratory
      distress, neurological disorders, viral load in blood and tissues, and gross
      lesions and antigen in target tissues; all animals in this group succumbed to
      infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2
      4 showed no evidence of clinical illness and survived challenged. All animals in
      these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers.
      While NiV RNA was detected in blood at day 6 post challenge in animals from
      Groups 2-4, the levels were orders of magnitude lower than animals from control
      Group 1. CONCLUSIONS: These data show protective efficacy against NiV in a
      relevant model of human infection. Further development of this technology has the
      potential to yield effective single injection vaccines for NiV infection.

PMID- 24330653
TI  - Coronary artery bypass grafting hemodynamics and anastomosis design: a biomedical
      engineering review.
AB  - In this paper, coronary arterial bypass grafting hemodynamics and anastomosis
      designs are reviewed. The paper specifically addresses the biomechanical factors
      for enhancement of the patency of coronary artery bypass grafts (CABGs). Stenosis
      of distal anastomosis, caused by thrombosis and intimal hyperplasia (IH), is the
      major cause of failure of CABGs. Strong correlations have been established
      between the hemodynamics and vessel wall biomechanical factors and the initiation
      and development of IH and thrombus formation. Accordingly, several investigations
      have been conducted and numerous anastomotic geometries and devices have been
      designed to better regulate the blood flow fields and distribution of hemodynamic
      parameters and biomechanical factors at the distal anastomosis, in order to
      enhance the patency of CABGs. Enhancement of longevity and patency rate of CABGs
      can eliminate the need for re-operation and can significantly lower morbidity,
      and thereby reduces medical costs for patients suffering from coronary stenosis.
      This invited review focuses on various endeavors made thus far to design a
      patency-enhancing optimized anastomotic configuration for the distal junction of
      CABGs. 

PMID- 24330655
TI  - BioSuper: a web tool for the superimposition of biomolecules and assemblies with
      rotational symmetry.
AB  - BACKGROUND: Most of the proteins in the Protein Data Bank (PDB) are oligomeric
      complexes consisting of two or more subunits that associate by rotational or
      helical symmetries. Despite the myriad of superimposition tools in the
      literature, we could not find any able to account for rotational symmetry and
      display the graphical results in the web browser. RESULTS: BioSuper is a free web
      server that superimposes and calculates the root mean square deviation (RMSD) of
      protein complexes displaying rotational symmetry. To the best of our knowledge,
      BioSuper is the first tool of its kind that provides immediate interactive
      visualization of the graphical results in the browser, biomolecule generator
      capabilities, different levels of atom selection, sequence-dependent and
      structure-based superimposition types, and is the only web tool that takes into
      account the equivalence of atoms in side chains displaying symmetry ambiguity.
      BioSuper uses ICM program functionality as a core for the superimpositions and
      displays the results as text, HTML tables and 3D interactive molecular objects
      that can be visualized in the browser or in Android and iOS platforms with a free
      plugin. CONCLUSIONS: BioSuper is a fast and functional tool that allows for
      pairwise superimposition of proteins and assemblies displaying rotational
      symmetry. The web server was created after our own frustration when attempting to
      superimpose flexible oligomers. We strongly believe that its user-friendly and
      functional design will be of great interest for structural and computational
      biologists who need to superimpose oligomeric proteins (or any protein). BioSuper
      web server is freely available to all users at http://ablab.ucsd.edu/BioSuper.

PMID- 24330656
TI  - Attentional bias retraining in cigarette smokers attempting smoking cessation
      (ARTS): study protocol for a double blind randomised controlled trial.
AB  - BACKGROUND: Smokers attend preferentially to cigarettes and other smoking-related
      cues in the environment, in what is known as an attentional bias. There is
      evidence that attentional bias may contribute to craving and failure to stop
      smoking. Attentional retraining procedures have been used in laboratory studies
      to train smokers to reduce attentional bias, although these procedures have not
      been applied in smoking cessation programmes. This trial will examine the
      efficacy of multiple sessions of attentional retraining on attentional bias,
      craving, and abstinence in smokers attempting cessation. METHODS/DESIGN: This is
      a double-blind randomised controlled trial. Adult smokers attending a 7-session
      weekly stop smoking clinic will be randomised to either a modified visual probe
      task with attentional retraining or placebo training. Training will start 1 week
      prior to quit day and be given weekly for 5 sessions. Both groups will receive 21
      mg transdermal nicotine patches for 8-12 weeks and withdrawal-orientated
      behavioural support for 7 sessions. Primary outcome measures are the change in
      attentional bias reaction time and urge to smoke on the Mood and Physical
      Symptoms Scale at 4 weeks post-quit. Secondary outcome measures include
      differences in withdrawal, time to first lapse and prolonged abstinence at 4
      weeks post-quit, which will be biochemically validated at each clinic visit.
      Follow-up will take place at 8 weeks, 3 months and 6 months post-quit.
      DISCUSSION: This is the first randomised controlled trial of attentional
      retraining in smokers attempting cessation. This trial could provide proof of
      principle for a treatment aimed at a fundamental cause of addiction. TRIAL
      REGISTRATION: Current Controlled Trials: ISRCTN54375405.

PMID- 24330657
TI  - Temperature-regulated expression of outer membrane proteins in Shigella flexneri.
AB  - BACKGROUND: Bacteria exist widely in a diversity of natural environments. In
      order to survive adverse conditions such as nutrient depletion, biochemical and
      biological disturbances, and high temperature, bacteria have developed a wide
      variety of coping mechanisms. Temperature is one of the most important factors
      that can enhance the expression of microbial proteins. This study was conducted
      to investigate how outer membrane proteins (OMPs) of the bacterium Shigella
      flexneri respond to stress, especially during fever when the host's body
      temperature is elevated. METHODS: OMPs of S. flexneri ATCC 12022 and clinical
      isolate SH057 were extracted from an overnight culture grown at 37, 38.5, and 40
      degrees C. Comparisons of the expressed proteins under the different growth
      conditions were based on equal numbers of bacterial cells loaded in the SDS-PAGE
      gels. Separated proteins were stained with Coomassie brilliant blue. Selected
      proteins showing increased expression at 38.5 and 40 degrees C were characterized
      by performing MALDI-ToF-ToF. RESULTS: Different degrees of expression were
      demonstrated for different proteins expressed at 37 degrees C compared to 38.5
      and 40 degrees C. The proteins with molecular sizes of 18.4, 25.6, and 57.0 kDa
      showed increased expression level at increasing temperature and were identified
      as Dps, WrbA, and PepA, respectively. CONCLUSION: This study revealed that
      strains of S. flexneri respond at the proteomic level during stress caused by
      elevated temperature by decreasing the expression of proteins, maintaining the
      level of important proteins, or enhancing the levels of proteins presumably
      involved in survival and virulence.

PMID- 24330658
TI  - Follow-up of the Schmallenberg Virus Seroprevalence in Belgian Cattle.
AB  - Schmallenberg virus (SBV), which emerged in Northwestern Europe in 2011, is an
      arthropod-borne virus affecting primarily ruminants. Based on the results of two
      cross-sectional studies conducted in the Belgian ruminant population during
      winter 2011-2012, we concluded that at the end of 2011, almost the whole
      population had already been infected by SBV. A second cross-sectional serological
      study was conducted in the Belgian cattle population during winter 2012-2013 to
      examine the situation after the 2012 transmission period and to analyse the
      change in immunity after 1 year. A total of 7130 blood samples collected between
      1st January and 28 February 2013 in 188 herds were tested for the presence of SBV
      specific antibodies. All sampled herds tested positive and within-herd
      seroprevalence was estimated at 65.66% (95% CI: 62.28-69.04). A statistically
      significant decrease was observed between the beginning and the end of 2012. On
      the other hand, age-cohort-specific seroprevalence stayed stable from 1 year to
      the other. During winter 2012-2013, calves between 6 and 12 months had a
      seroprevalence of 20.59% (95% CI: 15.34-25.83), which seems to be an indication
      that SBV was still circulating at least in some parts of Belgium during summer
      early autumn 2012. Results showed that the level of immunity against SBV of the
      animals infected has not decreased and remained high after 1 year and that the
      spread of the virus has slowed down considerably during 2012. This study also
      indicated that in the coming years, there are likely to be age cohorts of
      unprotected animals.

PMID- 24330659
TI  - The 3'-UTR of the adiponectin Q gene harbours susceptibility loci for
      atherosclerosis and its metabolic risk traits.
AB  - BACKGROUND: Adiponectin Q is a hormone that modulates several metabolic processes
      and contributes to the suppression of biochemical pathways leading to metabolic
      syndrome. Hence, polymorphic changes in the adiponectin Q (ADIPOQ) gene are
      likely to contribute to metabolic disorders, and consequently lead to
      atherosclerosis. In the present study, we performed a population-based
      association study for 8 SNPs in 4646 Saudi individuals (2339 CAD cases versus
      angiographed 2307 controls) by real-time PCR. METHODS: Linkage analysis was done
      by the Affymetrix Gene Chip array, sequencing by the MegaBACE DNA analysis system
      and genotyping accomplished by TaqMan chemistry with the Applied Biosystem real
      time Prism 7900HT Sequence Detection System. RESULTS: The rs2241766 (TG + GG)
      [Odds ratio(95% Confidence Interval = 1.35(1.01-1.72); p = 0.015] and rs9842733A
      > T [1.48(1.01-2.07); p = 0.042] were associated with hypertension [HTN; 3541
      cases vs 1101 controls), following adjustment for the presence of other
      cardiovascular risk traits. The rs2241766 (TG + GG) was further implicated in
      harbouring of low high density lipoprotein levels (LHDL; 1353 versus 2156
      controls) [1.35(1.10-1.67); p = 0.005], but lost its association with obesity
      after the adjustment for confounders. Besides, low high density lipoprotein was
      also linked with rs6444174 (TC + CC) [1.28(1.05-1.59)]. On the other hand, while
      initial univariate logistic regression analysis pointed to rs1063537 C > T (p =
      0.010), rs2082940 C > T (p = 0.035) and rs1063539 G > C (p = 0.035) as being
      associated with myocardial infarction, significance levels of these relationships
      were diminished following adjustment for the influence of confounding covariates.
      Interestingly, haplotyping showed that an 8-mer haplotype GTGCCTCA and several of
      its derivatives constructed from the studied SNPs were commonly implicated in MI
      (chi2 = 4.12; p = 0.042), HTN (chi2 = 6.40; p = 0.011) and OBS (chi2 = 5.18; p =
      0.023). CONCLUSION: These results demonstrate that the ADIPOQ 3'UTR harbours
      common susceptibility variants for metabolic risk traits and CAD, pointing to the
      importance of this region in atherosclerosis disease pathways.

PMID- 24330660
TI  - Morphological and molecular characterization and phylogenetic relationships of a
      new species of trypanosome in Tapirus terrestris (lowland tapir), Trypanosoma
      terrestris sp. nov., from Atlantic Rainforest of southeastern Brazi.
AB  - BACKGROUND: The Lowland tapir (Tapirus terrestris) is the largest Brazilian
      mammal and despite being distributed in various Brazilian biomes, it is seriously
      endangered in the Atlantic Rainforest. These hosts were never evaluated for the
      presence of Trypanosoma parasites. METHODS: The Lowland tapirs were captured in
      the Brazilian southeastern Atlantic Rainforest, Espirito Santo state.
      Trypanosomes were isolated by hemoculture, and the molecular phylogeny based on
      small subunit rDNA (SSU rDNA) and glycosomal-3-phosphate dehydrogenase (gGAPDH)
      gene sequences and the ultrastructural features seen via light microscopy and
      scanning and transmission electron microscopy are described. RESULTS:
      Phylogenetic trees using combined SSU rDNA and gGAPDH data sets clustered the
      trypanosomes of Lowland tapirs, which were highly divergent from other
      trypanosome species. The phylogenetic position and morphological discontinuities,
      mainly in epimastigote culture forms, made it possible to classify the
      trypanosomes from Lowland tapirs as a separate species. CONCLUSIONS: The isolated
      trypanosomes from Tapirus terrestris are a new species, Trypanosoma terrestris
      sp. n., and were positioned in a new Trypanosoma clade, named T. terrestris
      clade.

PMID- 24330661
TI  - Smad3 is required for the survival of proliferative intermediate progenitor cells
      in the dentate gyrus of adult mice.
AB  - BACKGROUND: New neurons are continuously being generated in the adult
      hippocampus, a phenomenon that is regulated by external stimuli, such as
      learning, memory, exercise, environment or stress. However, the molecular
      mechanisms underlying neuron production and how they are integrated into existing
      circuits under such physiological conditions remain unclear. Indeed, the
      intracellular modulators that transduce the extracellular signals are not yet
      fully understood. RESULTS: We show that Smad3, an intracellular molecule involved
      in the transforming growth factor (TGF)-beta signaling cascade, is strongly
      expressed by granule cells in the dentate gyrus (DG) of adult mice, although the
      loss of Smad3 in null mutant mice does not affect their survival. Smad3 is also
      expressed by adult progenitor cells in the subgranular zone (SGZ) and more
      specifically, it is first expressed by Type 2 cells (intermediate progenitor
      cells). Its expression persists through the distinct cell stages towards that of
      the mature neuron. Interestingly, proliferative intermediate progenitor cells die
      in Smad3 deficiency, which is associated with a large decrease in the production
      of newborn neurons in Smad3 deficient mice. Smad3 signaling appears to influence
      adult neurogenesis fulfilling distinct roles in the rostral and mid-caudal
      regions of the DG. In rostral areas, Smad3 deficiency increases proliferation and
      promotes the cell cycle exit of undifferentiated progenitor cells. By contrast,
      Smad3 deficiency impairs the survival of newborn neurons in the mid-caudal region
      of the DG at early proliferative stages, activating apoptosis of intermediate
      progenitor cells. Furthermore, long-term potentiation (LTP) after high frequency
      stimulation (HFS) to the medial perforant path (MPP) was abolished in the DG of
      Smad3-deficient mice. CONCLUSIONS: These data show that endogenous Smad3
      signaling is central to neurogenesis and LTP induction in the adult DG, these
      being two forms of hippocampal brain plasticity related to learning and memory
      that decline with aging and as a result of neurological disorders.

PMID- 24330662
TI  - Proteomic analysis of mismatch repair-mediated alkylating agent-induced DNA
      damage response.
AB  - BACKGROUND: Mediating DNA damage-induced apoptosis is an important genome
      maintenance function of the mismatch repair (MMR) system. Defects in MMR not only
      cause carcinogenesis, but also render cancer cells highly resistant to
      chemotherapeutics, including alkylating agents. To understand the mechanisms of
      MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a
      model alkylating agent (N-methyl-N'-nitro-N-nitrosoguanidine, MNNG)-induced
      changes in protein phosphorylation and abundance in two cell lines, the MMR
      proficient TK6 and its derivative MMR-deficient MT1. RESULTS: Under an
      experimental condition that MNNG-induced apoptosis was only observed in MutSa
      proficient (TK6), but not in MutSa-deficient (MT1) cells, quantitative analysis
      of the proteomic data revealed differential expression and phosphorylation of
      numerous individual proteins and clusters of protein kinase substrates, as well
      differential activation of response pathways/networks in MNNG-treated TK6 and MT1
      cells. Many alterations in TK6 cells are in favor of turning on the apoptotic
      machinery, while many of those in MT1 cells are to promote cell proliferation and
      anti-apoptosis. CONCLUSIONS: Our work provides novel molecular insights into the
      mechanism of MMR-mediated DNA damage-induced apoptosis.

PMID- 24330663
TI  - The prognostic values of EGFR expression and KRAS mutation in patients with
      synchronous or metachronous metastatic colorectal cancer.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway
      is an important pathway in the carcinogenesis, invasion and metastasis of
      colorectal cancers (CRCs). We conducted a retrospective study to determine the
      prognostic values of EGFR expression and KRAS mutation in patients with
      metastatic CRC (mCRC) based on synchronous or metachronous status. METHODS: From
      October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed;
      98 were found to have metachronous mCRC while 107 were found to have synchronous
      mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry)
      analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+
      (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and
      direct sequencing of KRAS was performed. The clinicopathological features of
      these mCRC patients were retrospectively investigated according to EGFR
      expression and KRAS mutation status. Moreover, we analyzed the prognostic values
      of EGFR expression and KRAS mutation among these patients. RESULTS: Of the 205
      patients with mCRC, EGFR expression was analyzed in 167 patients, and positive
      EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was
      investigated in 205 patients and mutations were noted in 88 of those patients
      (42.9%). In patients with metachronous mCRC, positive EGFR expression was
      significantly correlated with well-and moderately-differentiated tumors
      (P=0.028), poorer disease-free survival (DFS) (P<0.001), and overall survival
      (OS) (P<0.001). Furthermore, positive EGFR expression was a significant
      independent prognostic factor of DFS (P=0.006, HR: 4.012, 95% CI: 1.130-8.445)
      and OS (P=0.028, HR: 3.090, 95% CI: 1.477-10.900) in metachronous mCRC patients.
      KRAS mutation status was not significantly related to DFS and OS of patients with
      metachronous mCRC; likewise, KRAS mutation status was not significantly different
      in the progression-free survival (PFS) and OS of patients with synchronous mCRC
      (all P>0.05). CONCLUSIONS: The present study demonstrated that EGFR expression
      has prognostic value only for patients with metachronous mCRC. However, KRAS
      mutation did not have prognostic value in patients with metachronous or
      synchronous mCRC.

PMID- 24330664
TI  - Cartilage oligomeric matrix protein-induced complement activation in systemic
      sclerosis.
AB  - INTRODUCTION: Complexes between cartilage oligomeric matrix protein (COMP) and
      the complement activation product C3b have been found in the circulation of
      patients with rheumatoid arthritis and systemic lupus erythematosus. In systemic
      sclerosis (SSc) COMP expression in the skin is upregulated both in lesional and
      non-lesional skin, which is also reflected in an increased amount of circulating
      COMP. We investigated the presence of COMP-C3b complexes in serum and skin
      biopsies of patients with SSc. METHODS: The presence of COMP and COMP-C3b
      complexes in the serum of 80 patients with limited cutaneous SSc (lcSSc, n = 40)
      and diffuse cutaneous SSc (dcSSc, n = 40) and 97 healthy controls was measured by
      ELISA and correlated to different clinical parameters. Samples were collected
      both at baseline and after three to five years to assess longitudinal changes in
      COMP-C3b complex levels. Furthermore, skin biopsies from seven patients with
      dcSSc and three healthy controls were analyzed for expression of COMP and
      deposition of C3b and IgG. RESULTS: Serum levels of COMP-C3b were found to be
      elevated in both dcSSc and lcSSc compared to healthy controls and decreased at
      the second measurement in patients on immunosuppressive therapy. No co
      localization of COMP and C3b was found in the skin biopsies, indicating that the
      COMP-C3b complexes are formed upon release of COMP into the circulation.
      CONCLUSION: COMP-C3b complexes are found in the serum of patients with SSc. The
      lack of co-localization between COMP and C3b in the skin suggests that COMP does
      not drive complement activation in the skin in SSc.

PMID- 24330665
TI  - An improved multiple-locus variable-number of tandem repeat analysis (MLVA) for
      the fish pathogen Francisella noatunensis using capillary electrophoresis.
AB  - BACKGROUND: Francisellosis, caused by the bacterium Francisella noatunensis
      subsp. noatunensis, remains a serious threat to Atlantic cod (Gadhus morhua)
      farming in Norway and potentially in other countries. As outbreak strains appear
      clonal in population structure, access to highly discriminatory typing tools is
      critical for understanding the epidemiology of francisellosis infections in
      aquaculture. In this study, a simplified multiple-locus variable-number of tandem
      repeat analysis (MLVA) targeting five highly polymorphic variable number of
      tandem repeat (VNTR) loci in a single multiplex PCR was developed to rapidly
      discriminate between outbreak strains. RESULTS: The assay resulted in
      identification of at least 13 different allelic profiles or subpopulations among
      91 F. noatunensis isolates from farmed cod in Norway. The VNTR loci appear
      relatively stable, with isolates originating from individual outbreaks showing
      identical MLVA profiles following repeated passage. MLVA displayed greater
      discriminatory power than pulse-field gel electrophoresis (PFGE). Both MLVA and
      PFGE show good epidemiological concordance by their abilities to separate
      outbreak strains from epidemiologically unrelated isolates. CONCLUSIONS: The MLVA
      method presented here is robust, easy to perform and provides a good alternative
      to other typing systems for F. noatunensis subsp. noatunensis and epidemiological
      study of francisellosis in cod.

PMID- 24330666
TI  - An International Collaborative Study to establish the WHO 2nd International
      Standard for High Molecular Weight Urokinase: communication from SSC of the ISTH.

PMID- 24330667
TI  - Why are bacteria different from eukaryotes?

PMID- 24330668
TI  - miR394 and LCR are involved in Arabidopsis salt and drought stress responses in
      an abscisic acid-dependent manner.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of short, endogenous non-coding small
      RNAs that have ability to base pair with their target mRNAs to induce their
      degradation in plants. miR394a/b are conserved small RNAs and its target gene LCR
      (LEAF CURLING RESPONSIVENESS) encodes an F-box protein (SKP1-Cullin/CDC53-F-box)
      but whether miR394a/b and its target gene LCR are involved in regulation of plant
      response to abscisic acid (ABA) and abiotic stresses is unknown. RESULTS: Mature
      miR394 and precursor miR394a/b are shown to be slightly induced by ABA. By
      contrast, LCR expression is depressed by ABA. Analysis of LCR and its promoter
      (pLCR::GUS) revealed that LCR is expressed at all development stages. MIR394a/b
      over-expression (35S::MIR394a/b) and lcr (LCR loss of function) mutant plants are
      hypersensitive to salt stress, but LCR over-expressing (35S::m5LCR) plants
      display the salt-tolerant phenotype. Both 35S::MIR394a/b and lcr plants are
      highly tolerant to severe drought stress compared with wild-type, but 35S::m5LCR
      plants are susceptible to water deficiency. Over-expression of MIR394a/b led to
      ABA hypersensitivity and ABA-associated phenotypes, whereas 35S::m5LCR plants
      show ABA resistance phenotypes. Moreover, 35S::MIR394a/b plants accumulated
      higher levels of ABA-induced hydrogen peroxide and superoxide anion radicals than
      wild-type and 35S::m5LCR plants. Expressions of ABA- and stress-responsive genes,
      ABI3, ABI4, ABI5, ABF3, and ABF4 are up-regulated in MIR394a/b over-expressing
      plants but down-regulated in 35S::m5LCR plants. Over-expression of MIR394a in
      abi4-1 or abi5-1 background resulted in loss of ABA-sensitivity in 35S::MIR394a
      plants. CONCLUSIONS: The silencing of LCR mRNA by miR394 is essential to maintain
      a certain phenotype favorable for the adaptive response to abiotic stresses. The
      contrasting phenotypes of salt and drought responses may be mediated by a
      functional balance between miR394 and LCR. If the balance is perturbed in case of
      the abiotic stress, an identical phenotype related to the stress response occurs,
      resulting in either ABA sensitive or insensitive response. Thus, miR394-regulated
      LCR abundance may allow plants to fine-tune their responses to ABA and abiotic
      stress.

PMID- 24330669
TI  - Reducing disease burden and health inequalities arising from chronic disease
      among indigenous children: an early childhood caries intervention in Aotearoa/New
      Zealand.
AB  - BACKGROUND: Maaori are the Indigenous people of New Zealand and do not enjoy the
      same oral health status as the non-Indigenous majority. To overcome oral health
      disparities, the life course approach affords a valid foundation on which to
      develop a process that will contribute to the protection of the oral health of
      young infants. The key to this process is the support that could be provided to
      the parents or care givers of Maaori infants during the pregnancy of the mother
      and the early years of the child. This study seeks to determine whether
      implementing a kaupapa Maaori (Maaori philosophical viewpoint) in an early
      childhood caries (ECC) intervention reduces dental disease burden among Maaori
      children. The intervention consists of four approaches to prevent early childhood
      caries: dental care provided during pregnancy, fluoride varnish application to
      the teeth of children, motivational interviewing, and anticipatory guidance.
      METHODS/DESIGN: The participants are Maaori women who are expecting a child and
      who reside within the Maaori tribal area of Waikato-Tainui.This randomised
      control trial will be undertaken utilising the principles of kaupapa Maaori
      research, which encompasses Maaori leadership, Maaori relationships, Maaori
      customary practices, etiquette and protocol. Participants will be monitored
      through clinical and self-reported information collected throughout the ECC
      intervention. Self-report information will be collected in a baseline
      questionnaire during pregnancy and when children are aged 24 and 36 months.
      Clinical oral health data will be collected during standardised examinations at
      ages 24 and 36 months by calibrated dental professionals. All participants
      receive the ECC intervention benefits, with the intervention delayed by 24 months
      for participants who are randomised to the control-delayed arm. DISCUSSION: The
      development and evaluation of oral health interventions may produce evidence that
      supports the application of the principles of kaupapa Maaori research in the
      research processes. This study will assess an ECC intervention which could
      provide a meaningful approach for Maaori for the protection and maintenance of
      oral health for Maaori children and their family, thus reducing oral health
      disparities. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials
      Register (ANZCTR): ACTRN12611000111976.

PMID- 24330670
TI  - Effects of oral adenosine-5'-triphosphate supplementation on athletic
      performance, skeletal muscle hypertrophy and recovery in resistance-trained men.
AB  - BACKGROUND: Currently, there is a lack of studies examining the effects of
      adenosine-5'-triphosphate (ATP) supplementation utilizing a long-term, periodized
      resistance-training program (RT) in resistance-trained populations. Therefore, we
      investigated the effects of 12 weeks of 400 mg per day of oral ATP on muscular
      adaptations in trained individuals. We also sought to determine the effects of
      ATP on muscle protein breakdown, cortisol, and performance during an overreaching
      cycle. METHODS: The study was a 3-phase randomized, double-blind, and placebo-
      and diet-controlled intervention. Phase 1 was a periodized resistance-training
      program. Phase 2 consisted of a two week overreaching cycle in which volume and
      frequency were increased followed by a 2-week taper (Phase 3). Muscle mass,
      strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic
      effects of ATP; assessment performance variables also occurred at the end of
      weeks 9 and 10, corresponding to the mid and endpoints of the overreaching cycle.
      RESULTS: There were time (p<0.001), and group x time effects for increased total
      body strength (+55.3 +/- 6.0 kg ATP vs. + 22.4 +/- 7.1 kg placebo, p<0.001);
      increased vertical jump power (+ 796 +/- 75 ATP vs. 614 +/- 52 watts placebo,
      p<0.001); and greater ultrasound determined muscle thickness (+4.9 +/- 1.0 ATP
      vs. (2.5 +/- 0.6 mm placebo, p<0.02) with ATP supplementation. During the
      overreaching cycle, there were group x time effects for strength and power, which
      decreased to a greater extent in the placebo group. Protein breakdown was also
      lower in the ATP group. CONCLUSIONS: Our results suggest oral ATP supplementation
      may enhance muscular adaptations following 12-weeks of resistance training, and
      prevent decrements in performance following overreaching. No statistically or
      clinically significant changes in blood chemistry or hematology were observed.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01508338.

PMID- 24330671
TI  - Literacy and healthcare-seeking among women with low educational attainment:
      analysis of cross-sectional data from the 2011 Nepal Demographic and Health
      Survey.
AB  - INTRODUCTION: Research suggests that literacy plays a key role in mediating the
      relationship between formal education and care-seeking among women in developing
      countries. However, little research has examined literacy's role independently
      from formal education. This differentiation is important, as literacy programs
      and formal schooling entail distinct intervention designs and resources, and may
      target different groups. To assess the relationship between literacy and
      healthcare-seeking among Nepali women of low educational attainment, we analyzed
      data from the 2011 Nepal Demographic and Health Survey (DHS). METHODS: From the
      2011 Nepal DHS, our sample consisted of 7,020 women who had attained at most a
      primary school level of education, and a subsample of 4,875 women with no formal
      schooling whatsoever. We assessed associations between literacy and four
      healthcare-seeking outcomes: whether women identified "getting permission" as a
      barrier to accessing care; whether women identified "not wanting to go alone" as
      a barrier; whether among women who were married/partnered, the woman had some say
      in making decisions about her own health; and whether among women who experienced
      symptoms related to sexually-transmitted infections (STIs) in the past year,
      treatment was sought. We performed simple and multiple logistic regressions,
      which adjusted for several socio-demographic covariates. RESULTS: Literacy was
      associated with some aspects of healthcare-seeking, even after adjusting for
      socio-demographic covariates. Among women with no more than primary schooling,
      literate women's odds of identifying "getting permission" as a barrier to
      healthcare were 23% less than illiterate women's odds (p = 0.04). For
      married/partnered women, odds of having some say in making decisions related to
      their health were 37% higher (p = 0.002) in literate than illiterate women.
      Comparing literate to illiterate women in the subsample with no formal schooling,
      odds of reporting "getting permission" as a barrier were 35% lower (p = 0.01),
      odds of having a decision-making say were 57% higher (p < 0.001), and odds of
      having sought care for experiences of STI-related symptoms were 86% higher (p =
      0.04). CONCLUSIONS: Further research should be undertaken to determine whether
      targeted literacy programs for those past normal schooling age lead to improved
      healthcare-seeking among Nepali women with little or no formal education.

PMID- 24330672
TI  - Impending paradoxical embolism: have we lost the clot?
AB  - Impending paradoxical embolism is a rare diagnosis that requires urgent
      treatment. We present a case where surgical thromboembolectomy was undertaken.
      The thrombus vanished from view on transesophageal ultrasound and was presumed to
      have undergone embolisation while bypass was established. Unexpectedly, it was
      found tangled in the superior vena cava cannula apertures. 

PMID- 24330673
TI  - Serogroups, virulence genes and antibiotic resistance in Shiga toxin-producing
      Escherichia coli isolated from diarrheic and non-diarrheic pediatric patients in
      Iran.
AB  - BACKGROUND: From a clinical perspective, it is important to know which
      serogroups, virulence genes and antibiotic resistance patterns are present in
      Shiga toxin-producing Escherichia coli strains in pediatric patients suffering
      from diarrheic and non-diarrheic infections. This is the first study in Iran that
      has comprehensively investigated the Shiga toxin-producing Escherichia coli 
      related infection characteristics in diarrheic and non-diarrheic pediatric
      patients of 0-60 months of age. METHODS: Two-hundred and twenty four diarrheic
      and 84 non-diarrheic stool specimens were collected from the Baqiyatallah
      hospital of Tehran, Iran. The stool samples were cultured immediately and those
      that were E. coli-positive were analyzed for the presence of antibiotic
      resistance genes and bacterial virulence factors using PCR. Antimicrobial
      susceptibility testing was performed using disk diffusion method. RESULTS: One
      hundred and fifty four out of 224 (68.75%) diarrheic stools and 31 out of 84
      (36.90%) non-diarrheic stools harbored E. coli. In addition, children in 13-24
      month-old age group had the highest incidence of infection with this bacterium
      (77.63%). A significant difference was found between the frequency of Attaching
      and Effacing Escherichia coli and Enterohaemorrhagic Escherichia coli (P =0.045).
      The genes encoding Shiga toxins and intimin were the most commonly detected
      virulence factors. Among all serogroups studied, O26 (27.04%) and O111 (18.85%)
      had the highest incidences in the diarrheic and non-diarrheic patients. The
      incidence of genes encoding resistance against sulfonamide (sul1), gentamicin
      (aac(3)-IV), trimethoprim (aadA1), cephalothin (blaSHV) and tetracycline (tetA)
      were 82.78%, 68.03%, 60.65%, 56.55% and 51.63%, respectively. High resistance
      levels against penicillin (100%), tetracycline (86.88%), gentamicin (62.29%) and
      streptomycin (54.91%) were observed. Marked seasonality in the serogroup
      distributions was evident, while STEC infections were more common in summer (P
      =0.041). CONCLUSIONS: Our findings should raise awareness about antibiotic
      resistance in diarrheic pediatric patients in Iran. Clinicians should exercise
      caution when prescribing antibiotics, especially during the warmer months of the
      year.

PMID- 24330674
TI  - Identification of two putative reference genes from grapevine suitable for gene
      expression analysis in berry and related tissues derived from RNA-Seq data.
AB  - BACKGROUND: Data normalization is a key step in gene expression analysis by qPCR.
      Endogenous control genes are used to estimate variations and experimental errors
      occurring during sample preparation and expression measurements. However, the
      transcription level of the most commonly used reference genes can vary
      considerably in samples obtained from different individuals, tissues,
      developmental stages and under variable physiological conditions, resulting in a
      misinterpretation of the performance of the target gene(s). This issue has been
      scarcely approached in woody species such as grapevine. RESULTS: A statistical
      criterion was applied to select a sub-set of 19 candidate reference genes from a
      total of 242 non-differentially expressed (NDE) genes derived from a RNA-Seq
      experiment comprising ca. 500 million reads obtained from 14 table-grape
      genotypes sampled at four phenological stages. From the 19 candidate reference
      genes, VvAIG1 (AvrRpt2-induced gene) and VvTCPB (T-complex 1 beta-like protein)
      were found to be the most stable ones after comparing the complete set of
      genotypes and phenological stages studied. This result was further validated by
      qPCR and geNorm analyses. CONCLUSIONS: Based on the evidence presented in this
      work, we propose to use the grapevine genes VvAIG1 or VvTCPB or both as a
      reference tool to normalize RNA expression in qPCR assays or other quantitative
      method intended to measure gene expression in berries and other tissues of this
      fruit crop, sampled at different developmental stages and physiological
      conditions.

PMID- 24330675
TI  - Dyspepsia and gastric emptying in end-stage renal disease patients on
      hemodialysis.
AB  - BACKGROUND: Dyspepsia is common among end-stage renal disease (ESRD) patients and
      its association with delayed gastric emptying is not well established. We
      assessed the association of dyspepsia with gastric emptying time in ESRD patients
      undergoing hemodialysis (HD). METHODS: Dyspepsia was assessed through the Porto
      Alegre Dyspeptic Symptoms Questionnaire (PADYQ). PADYQ's scores >= 6 classified
      participants as dyspeptic. The octanoic acid breath test using 13carbon was
      employed to assess the gastric emptying time. Based on the test, time in minutes
      to metabolize the first half of the 13carbon in the test meal (t1/2) was
      calculated. Association of dyspepsia with gastric emptying time was tested by the
      correlation between PADYQ scores and t1/2, and also by comparing t1/2 between
      dyspeptics and non-dyspeptics. RESULTS: There were 34 (68.0%) dyspeptic patients.
      Dyspepsia score was positively correlated with t1/2 (r = 0.366; p = 0.009).
      Dyspeptics had longer t1/2 compared to non-dyspeptics, respectively, 238.0 +/-
      92.9 versus 185.5 +/- 45.5 minutes (p = 0.042). CONCLUSIONS: Delayed gastric
      emptying was associated with dyspepsia. Prokinetic medications could have a role
      in preventing or relieving dyspeptic symptoms among HD patients. Future research
      in larger samples is necessary to confirm this association.

PMID- 24330676
TI  - Paediatric palliative care: development and pilot study of a 'Directory' of life
      limiting conditions.
AB  - BACKGROUND: Children's palliative care services are developing. Rational service
      development requires sound epidemiological data that are difficult to obtain
      owing to ambiguity in the definitions both of the population who needs palliative
      care and of palliative care itself. Existing definitions are of trajectory
      archetypes. The aim of this study was to develop and pilot a directory of the
      commonest specific diagnoses that map on to those archetypes. METHODS: The
      diagnoses of patients under the care of five children hospices and a tertiary
      specialist palliative medicine service in the UK were recorded. Duplicates and
      diagnoses that were not life-limiting conditions according to the ACT/RCPCH
      criteria or were not primary were removed. The resulting Directory of life
      limiting conditions was piloted by analysing Death Certificate data of children
      in Wales between 2002 and 2007. RESULTS: 1590 diagnoses from children's hospices
      and 105 from specialist palliative medicine were combined. After removals there
      were 376 diagnostic label. All ICD10 chapter headings were represented by at
      least one condition. The pilot study showed that 569 (54%) deaths in Wales were
      caused by LLC. Only four LLC resulted in ten or more deaths. Among deaths from
      LLC, the ten commonest diagnoses accounted for 32%, while the 136 diagnoses that
      caused one or two deaths accounted for 25%. The majority occurred from a small
      number of life-limiting conditions. CONCLUSION: The Directory is a practical tool
      for identifying most life-limiting conditions using ICD10 codes that facilitates
      extraction and analysis of data from existing sources in respect of life-limiting
      conditions in children such as death certificate data, offering the potential for
      rapid and precise studies in paediatric palliative care.

PMID- 24330677
TI  - The FAt Spondyloarthritis Spine Score (FASSS): development and validation of a
      new scoring method for the evaluation of fat lesions in the spine of patients
      with axial spondyloarthritis.
AB  - INTRODUCTION: Studies have shown that fat lesions follow resolution of
      inflammation in the spine of patients with axial spondyloarthritis (SpA). Fat
      lesions at vertebral corners have also been shown to predict development of new
      syndesmophytes. Therefore, scoring of fat lesions in the spine may constitute
      both an important measure of treatment efficacy as well as a surrogate marker for
      new bone formation. The aim of this study was to develop and validate a new
      scoring method for fat lesions in the spine, the Fat SpA Spine Score (FASSS),
      which in contrast to the existing scoring method addresses the localization and
      phenotypic diversity of fat lesions in patients with axial SpA. METHODS: Fat
      lesions at pre-specified anatomical locations at each vertebral endplate (C2
      lower-S1 upper) were assessed dichotomously (present/absent) on spine MRIs. Two
      readers independently evaluated MRIs obtained at two time points for 58 patients
      (Exercise 1), followed by optimization of scoring methodology and reader
      calibration. Thereafter, the same readers read 135 pairs of MRI scans (Exercise
      2; including the 58 pairs from exercise 1 randomly mixed with 77 new pairs).
      RESULTS: In Exercise 2, the mean (SD) baseline FASSS score for the two readers
      was 22.5(29.6) and 21.1(28.0), respectively, and the FASSS change score was
      4.2(10.6) and 6.0(12.2). Inter-reader reliability assessed as intra-class
      correlation coefficients (ICCs) for status and change scores were excellent (0.96
      (95% CI (0.94 to 0.97)) and very good (0.86 (0.80 to 0.90)), respectively. The
      smallest detectable change (SDC) was 3.7 for the 135 patients. Good reliability
      of change scores was also observed for MRI scans conducted one year apart (ICC
      0.74 (95% CI 0.44 to 0.89) and SDC 4.5). For the 58 MRI-pairs assessed in both
      exercises, inter-reader reproducibility for the total FASSS status score improved
      from very good (ICCs: 0.89 (95% CI: 0.81 to 0.93) in exercise 1 to excellent in
      exercise 2 (0.96 (0.93 to 0.98)), and improved substantially for the total change
      score (from 0.67 (0.51 to 0.80) to 0.83 (0.73 to 0.90). CONCLUSIONS: FASSS meets
      essential validation criteria for quantification of a common structural
      abnormality in clinical trials of axial spondyloarthritis.

PMID- 24330680
TI  - Resveratrol induces insulin gene expression in mouse pancreatic alpha-cells.
AB  - BACKGROUND: Type 1 and type 2 diabetes are characterized by loss of beta-cells;
      therefore, beta-cell regeneration has become one of the primary approaches to
      diabetes therapy. Resveratrol, a naturally occurring polyphenolic compound, has
      been shown to improve glycaemic control in diabetic patients, but its action on
      pancreatic alpha-cells is not well understood. FINDINGS: Using mouse alpha-cells
      (alphaTC9), we showed that resveratrol induces expression of pancreatic beta-cell
      genes such as Pdx1 and Ins2 in a SirT1-dependent manner. The mRNA and protein
      levels of insulin were further increased by histone deacetylase (HDAC)
      inhibition. CONCLUSION: In summary, we provide new mechanistic insight into the
      anti-diabetic action of resveratrol through its ability to express beta-cell
      genes in alpha-cells.

PMID- 24330679
TI  - Competence, commitment and opportunity: an exploration of faculty views and
      perceptions on community- based education.
AB  - BACKGROUND: Community-Based Education (CBE) is an instructional approach designed
      and carried out in a community context and environment in which not only
      students, but also faculty and Health Professionals' Education (HPE) institutions
      must be actively engaged throughout the educational experience. Despite the
      growing evidence of CBE being an effective approach for contemporary HPE, doubts
      about its successful implementation still exist. This study has explored HPE
      structure, policies and curriculum from the point of view of faculty members to
      gain understanding about the prevailing practices and to propose recommendations
      that nurtures and promotes CBE. METHOD: A purposive sample was drawn from three
      major cities of Pakistan- Karachi, Rawalpindi and Islamabad. Out of twelve HPE
      institutions present in these cities we selected six, which provided a sound
      representation of medical and nursing colleges around the country. At each
      institution we had two Focus Group Discussions; in addition we interviewed
      registrars of medical and nursing councils and two CBE experts. RESULTS: The
      factors effecting implementation of CBE as perceived by study participants are
      categorized as: preparation of faculty members; institutional commitment and
      enthusiasm; curricular priorities and external milieu. Within each theme,
      participants recurrently described structural and curricular deficiencies, and
      lack of commitment and appreciation for community based teaching, service and
      research permeating at all levels: regulatory bodies, institutional heads and
      faculty members. CONCLUSIONS: The factors highlighted by our study and many
      others suggest that CBE could not perpetuate effectively within HPE. To enhance
      the effectiveness of CBE approach in a way that mutually benefits local
      communities as well as HPE institutions and health professionals, it is important
      that reforms in HPE must be strategized in a holistic fashion i.e. restructuring
      and aligning its polices, curriculum and research priorities.

PMID- 24330678
TI  - Cell adhesion and intracellular calcium signaling in neurons.
AB  - Cell adhesion molecules (CAMs) play indispensable roles in the developing and
      mature brain by regulating neuronal migration and differentiation, neurite
      outgrowth, axonal fasciculation, synapse formation and synaptic plasticity. CAM
      mediated changes in neuronal behavior depend on a number of intracellular
      signaling cascades including changes in various second messengers, among which
      CAM-dependent changes in intracellular Ca2+ levels play a prominent role. Ca2+ is
      an essential secondary intracellular signaling molecule that regulates
      fundamental cellular functions in various cell types, including neurons. We
      present a systematic review of the studies reporting changes in intracellular
      Ca2+ levels in response to activation of the immunoglobulin superfamily CAMs,
      cadherins and integrins in neurons. We also analyze current experimental evidence
      on the Ca2+ sources and channels involved in intracellular Ca2+ increases
      mediated by CAMs of these families, and systematically review the role of the
      voltage-dependent Ca2+ channels (VDCCs) in neurite outgrowth induced by
      activation of these CAMs. Molecular mechanisms linking CAMs to VDCCs and
      intracellular Ca2+ stores in neurons are discussed. 

PMID- 24330681
TI  - Hepatosplenic gamma delta T-cell lymphoma in a boy with visceral leishmaniasis: a
      case report.
AB  - INTRODUCTION: Hepatosplenic gamma delta T-cell lymphoma is a rare peripheral T
      cell lymphoma of cytotoxic T-cell origin with an aggressive clinical course.
      Chronic immunosuppression has been proposed as a possible pathogenetic mechanism.
      No association of hepatosplenic gamma delta T-cell lymphoma with visceral
      leishmaniasis has been described in the past. We describe a case of an adolescent
      boy with hepatosplenic gamma delta T-cell lymphoma with leukemic presentation,
      who was diagnosed to have visceral leishmaniasis, 9 months prior to presentation
      at our center. To the best of our knowledge this is the first report of
      hepatosplenic gamma delta T-cell lymphoma with a prior history of visceral
      leishmaniasis in the medical literature. CASE PRESENTATION: A 13-year-old Indian
      boy presented to the hematology out-patient department with a history of
      progressive abdominal distension of 9 months' duration and low grade fever of 2
      months' duration. He was a known case of visceral leishmaniasis and was treated
      with some clinical improvement in the past. However, his symptoms recurred and he
      was diagnosed to have hepatosplenic gamma delta T-cell lymphoma at our center.
      Cytogenetic analysis showed characteristic karyotype of isochromosome 7.
      CONCLUSIONS: Chronic antigen stimulation due to visceral leishmaniasis may have
      led to an expansion of gamma delta T cells in our patient, and immunophenotypic
      analysis of bone marrow aspirate and characteristic karyotype helped to achieve
      the diagnosis. The aim of this case report is to highlight the rare association
      of hepatosplenic T-cell lymphoma with visceral leishmaniasis.

PMID- 24330682
TI  - Mycoplasma conjunctivae in domestic small ruminants from high mountain habitats
      in Northern Spain.
AB  - BACKGROUND: Infectious keratoconjunctivitis (IKC) is a clinical condition
      affecting eyes of domestic and wild Caprinae worldwide, and Mycoplasma
      conjunctivae is considered the primary causative agent of IKC in sheep, goats and
      wild Caprinae. Domestic ruminants from high mountain habitats share grazing areas
      with wild mountain ungulates, such as chamois (Rupicapra spp.), Alpine ibex
      (Capra ibex) and European mouflon (Ovis aries musimon), and domestic sheep seem
      to act as M. conjunctivae reservoir. In this study, the presence of M.
      conjunctivae in domestic sheep and goats from the two main mountain ranges of
      Northern Spain, the Pyrenees and the Cantabrian Mountains, has been investigated.
      RESULTS: Eye swabs were obtained from 439 domestic small ruminants selected from
      flocks that seasonally graze in alpine meadows during three consecutive years
      (2011-2012-2013). Seventy-nine out of the 378 domestic sheep (20.9%) tested
      positive to a M. conjunctivae specific real time-PCR (rt-PCR) in at least one
      eye, whereas all the 61 sampled domestic goats were negative. Statistically
      significant higher prevalence and higher proportion of infected flocks (P <
      0.001) was observed in the Pyrenees (25.7%; 12 flocks out of 13), where M.
      conjunctivae is widespread and probably endemic in domestic sheep, than in the
      Cantabrian Mountains (7.8%; one flock out of six). Twenty-five sheep (three from
      the Pyrenees and 22 from the Cantabrian Mountains) which showed clinical signs
      consistent with infectious keratoconjunctivitis (IKC) were negative by rt-PCR. In
      contrast, 62 out of the 71 (87.3%) M. conjunctivae-positive sheep from the
      Pyrenees and the eight positive sheep from the Cantabrian Mountains were
      asymptomatic. CONCLUSIONS: This study provides rt-PCR-based evidences of M.
      conjunctivae maintenance in domestic sheep, as well as a relationship between
      prevalence in domestic sheep and previously reported M. conjunctivae and IKC in
      wild ruminants. Domestic goats do not seem to play an important role in the
      epidemiology of M. conjunctivae in alpine habitats from Northern Spain.

PMID- 24330683
TI  - DAYSLEEPER: a nuclear and vesicular-localized protein that is expressed in
      proliferating tissues.
AB  - BACKGROUND: DAYSLEEPER is a domesticated transposase that is essential for
      development in Arabidopsis thaliana [Nature, 436:282-284, 2005]. It is derived
      from a hAT-superfamily transposon and contains many of the features found in the
      coding sequence of these elements [Nature, 436:282-284, 2005, Genetics, 158:949
      957, 2001]. This work sheds light on the expression of this gene and localization
      of its product in protoplasts and in planta. Using deletion constructs, important
      domains in the protein were identified. RESULTS: DAYSLEEPER is predominantly
      expressed in meristems, developing flowers and siliques. The protein is mainly
      localized in the nucleus, but can also be seen in discrete foci in the cytoplasm.
      Using several vesicular markers, we found that these foci belong to vesicular
      structures of the trans-golgi network, multivesicular bodies (MVB's) and late
      endosomes. The central region as well as both the N- and the C-terminus are
      essential to DAYSLEEPER function, since versions of DAYSLEEPER deleted for these
      regions are not able to complement the daysleeper phenotype. Like hAT
      transposases, we show that DAYSLEEPER has a functionally conserved dimerization
      domain [J Biol Chem, 282:7563-7575, 2007]. CONCLUSIONS: DAYSLEEPER has retained
      the global structure of hAT transposases and it seems that most of these
      conserved features are essential to DAYSLEEPER's cellular function. Although
      structurally similar, DAYSLEEPER seems to have broadened its range of action
      beyond the nucleus in comparison to transposases.

PMID- 24330684
TI  - Stigma towards a neglected tropical disease: felt and enacted stigma scores among
      podoconiosis patients in Northern Ethiopia.
AB  - BACKGROUND: Podoconiosis, or non-filarial elephantiasis, is a neglected tropical
      disease (NTD) characterised by swelling of the lower legs. When left untreated,
      this disfiguring condition has a significant social impact. This study aimed to
      describe the stigma experience among podoconiosis patients in Dembecha, Northern
      Ethiopia and assess potential associations between stigma and sociodemographic
      determinants. METHODS: The study was conducted in May 2012 in Northern Ethiopia.
      A questionnaire-based cross-sectional study design was used and stigma was
      assessed using a validated podoconiosis stigma scale including 'felt' and
      'enacted' stigma domains. Enacted stigma includes the experience of
      discrimination such as abuse, loss of employment or prejudicial attitudes, while
      felt stigma is the perceived fear of enacted stigma. A multivariable linear
      regression model was used to explore determinants that may be associated with
      stigma. RESULTS: A total of 346 clinically confirmed podoconiosis patients
      participated in the study. The total mean score of all stigma scale items was
      30.7 (Range = 0 to 96). There was a higher mean score of scale items in domains
      of felt stigma (21.7; Range = 0 to 45) as compared to enacted stigma (9.0; Range
      = 0 to 51). The total mean score of all stigma scale items appeared to increase
      with disease stage. A final adjusted linear regression model found an association
      between stigma and factors including monthly income, duration lived in the
      current residence, and disease stage, after controlling for confounders.
      CONCLUSION: Podoconiosis is a stigmatized disease with a clear social impact.
      This paper documented the burden of podoconiosis-related stigma and identified
      associated factors. Programs aimed at preventing and treating podoconiosis should
      incorporate interventions to mitigate both felt and enacted stigma. Interventions
      targeting patients should prioritize those with advanced disease.

PMID- 24330686
TI  - Academic medical centers: too big to fail.

PMID- 24330687
TI  - Guidelines for community-based partners for reviewing research grant
      applications: lessons from the Michigan Institute for Clinical and Health
      Research (MICHR) Community Engagement Research Core (CERC).

PMID- 24330688
TI  - Do clinical and translational science graduate students understand linear
      regression? Development and early validation of the REGRESS quiz.
AB  - INTRODUCTION: Although regression is widely used for reading and publishing in
      the medical literature, no instruments were previously available to assess
      students' understanding. The goal of this study was to design and assess such an
      instrument for graduate students in Clinical and Translational Science and Public
      Health. METHODS: A 27-item REsearch on Global Regression Expectations in
      StatisticS (REGRESS) quiz was developed through an iterative process. Consenting
      students taking a course on linear regression in a Clinical and Translational
      Science program completed the quiz pre- and postcourse. Student results were
      compared to practicing statisticians with a master's or doctoral degree in
      statistics or a closely related field. RESULTS: Fifty-two students responded
      precourse, 59 postcourse , and 22 practicing statisticians completed the quiz.
      The mean (SD) score was 9.3 (4.3) for students precourse and 19.0 (3.5)
      postcourse (P < 0.001). Postcourse students had similar results to practicing
      statisticians (mean (SD) of 20.1(3.5); P = 0.21). Students also showed
      significant improvement pre/postcourse in each of six domain areas (P < 0.001).
      The REGRESS quiz was internally reliable (Cronbach's alpha 0.89). CONCLUSION: The
      initial validation is quite promising with statistically significant and
      meaningful differences across time and study populations. Further work is needed
      to validate the quiz across multiple institutions.

PMID- 24330689
TI  - The quantitative evaluation of the Clinical and Translational Science Awards
      (CTSA) program based on science mapping and scientometric analysis.
AB  - The Clinical and Translational Science Awards (CTSA) program is one of the most
      important initiatives in translational medical funding. The quantitative
      evaluation of the efficiency and performance of the CTSA program has a
      significant referential meaning for the decision making of global translational
      medical funding. Using science mapping and scientometric analytic tools, this
      study quantitatively analyzed the scientific articles funded by the CTSA program.
      The results of the study showed that the quantitative productivities of the CTSA
      program had a stable increase since 2008. In addition, the emerging trends of the
      research funded by the CTSA program covered clinical and basic medical research
      fields. The academic benefits from the CTSA program were assisting its members to
      build a robust academic home for the Clinical and Translational Science and to
      attract other financial support. This study provided a quantitative evaluation of
      the CTSA program based on science mapping and scientometric analysis. Further
      research is required to compare and optimize other quantitative methods and to
      integrate various research results. 

PMID- 24330690
TI  - Publication track records as a metric of clinical research training
      effectiveness.
AB  - Clinical research training programs exist across the country, but no quantitative
      studies have been performed to evaluate the effectiveness of these programs. The
      goal of this study was to evaluate the success of the clinical research training
      program at the University of Cincinnati by comparing the publication histories of
      pediatric fellows who graduated from the clinical and translational research
      Master of Science (MS) degree programs between 1995 and 2011 with fellows who did
      not pursue an MS degree. Among 296 pediatric fellows, 44 of 54 graduates (81%)
      published at least 1 first-authored paper, as compared with 149 of 242 (62%)
      fellows who did not obtain an MS degree (P < 0.01). In multivariable analysis, 3
      4 years after program completion, MS graduates published more papers overall
      (R(2) = 0.10) and more first-authored papers than did non-MS graduates (R(2) =
      0.04). These findings suggest that graduate training in clinical and
      translational research is related to an increase in research productivity as
      assessed by publication rates. 

PMID- 24330691
TI  - Sildenafil increases muscle protein synthesis and reduces muscle fatigue.
AB  - Reductions in skeletal muscle function occur during the course of healthy aging
      as well as with bed rest or diverse diseases such as cancer, muscular dystrophy,
      and heart failure. However, there are no accepted pharmacologic therapies to
      improve impaired skeletal muscle function. Nitric oxide may influence skeletal
      muscle function through effects on excitation-contraction coupling, myofibrillar
      function, perfusion, and metabolism. Here we show that augmentation of nitric
      oxide-cyclic guanosine monophosphate signaling by short-term daily administration
      of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis,
      alters protein expression and nitrosylation, and reduces fatigue in human
      skeletal muscle. These findings suggest that phosphodiesterase 5 inhibitors
      represent viable pharmacologic interventions to improve muscle function. 

PMID- 24330693
TI  - Real-time RT-PCR Ct values for blood GAPDH correlate with measures of vascular
      endothelial function in humans.
AB  - PURPOSE: To date, there is a wide range of methods in use to assess endothelial
      function, each with its own advantages and limitations. Here, we tested
      hypothesis that real-time RT-PCR threshold value (Ct), which is reflective of
      mRNA level, for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from whole blood
      is indicative of endothelial function in humans. MATERIALS AND METHODS: To assess
      vascular function, we measured baseline skin perfusion, postocclusion reactive
      hyperemia (PORH), and brachial artery flow-mediated dilatation (FMD) and tested
      for a possible correlation between vascular responses and blood GAPDH real-time
      RT-PCR Ct value in 75 healthy volunteers. RESULTS: Tests known to measure, at
      least in part, endothelial function such as baseline skin perfusion, the 2-minute
      recovery PORH, and FMD exhibited significant positive correlations with blood
      GAPDH Ct values. In contrast, there was no significant correlation between Ct
      values for blood GAPDH and peak PORH, an endothelium-independent parameter.
      CONCLUSIONS: Based on these findings, we report that GAPDH mRNA level in the
      blood correlates with vascular function in healthy subjects. This suggests that
      GAPDH mRNA level could be a potential biomarker of vascular endothelial function.

PMID- 24330692
TI  - Value of impedance cardiography during 6-minute walk test in pulmonary
      hypertension.
AB  - BACKGROUND: Methods that predict prognosis and response to therapy in pulmonary
      hypertension (PH) are lacking. We tested whether the noninvasive estimation of
      hemodynamic parameters during 6-minute walk test (6MWT) in PH patients provides
      information that can improve the value of the test. METHODS: We estimated
      hemodynamic parameters during the 6MWT using a portable, signal-morphology-based,
      impedance cardiograph (PhysioFlow Enduro) with real-time wireless monitoring via
      a bluetooth USB adapter. RESULTS: We recruited 48 subjects in the study (30 with
      PH and 18 healthy controls). PH patients had significantly lower maximum stroke
      volume (SV) and CI and slower cardiac output (CO) acceleration and decelerations
      slopes during the test when compared with healthy controls. In PH patients, CI
      change was associated with total distance walked (R = 0.62; P < 0.001) and
      percentage of predicted (R = 0.4, P = 0.03), HR recovery at 1 minute (0.57, P <
      0.001), 2 minutes (0.65, P < 0.001), and 3 minutes (0.66, P < 0.001).
      Interestingly, in PH patients CO change during the test was predominantly related
      to an increase in SV instead of HR. CONCLUSIONS: Estimation of hemodynamic
      parameters such as cardiac index during 6-minute walk test is feasible and may
      provide useful information in patients with PH. Clin Trans Sci 2013; Volume #: 1
      7.

PMID- 24330694
TI  - Rate of change of carotid intima-media thickness with magnesium administration in
      Abcc6-/- mice.
AB  - Pseudoxanthoma elasticum (PXE), caused by mutations in the ABCC6 gene,
      demonstrates progressive build-up of calcium phosphate and proteoglycans in the
      skin, eye, and arteries, and is associated to myocardial infarctions, stroke,
      blindness, and elevated carotid intima-media thickness (CIMT). Although CIMT
      reduction with magnesium (Mg) has been documented in a mouse model for PXE
      (Abcc6(-/-) ), it is not clear if Mg is effective in humans with PXE to reduce
      CIMT. To examine this, we calculated the rate of change of CIMT (washout) in 15-
      and 12-month-old Abcc6(-/-) mice fed standard rodent diet with or without Mg
      supplementation for 2 months. Using means in untreated 15- and 12-month-old
      Abcc6(-/-) mice (145 and 120 MUm, respectively), the rate of change was 8.3
      MUm/month. Using means in treated 15- and 12-month-old Abcc6(-/-) mice (118 and
      104.6 MUm, respectively), the rate of change was 4.5 MUm. Compared to normal
      progression of CIMT in humans without PXE, PXE has advanced atherosclerosis and
      possibly a higher CIMT rate of change. This experiment may portend, at least in
      PXE, the rationale for a 1-year oral Mg CIMT clinical trial and may be useful for
      application in other progressive mineralizing disorders like atherosclerosis. 

PMID- 24330695
TI  - Summer research training for medical students: impact on research self-efficacy.
AB  - There is a well-documented shortage of physician researchers, and numerous
      training programs have been launched to facilitate development of new physician
      scientists. Short-term research training programs are the most practical form of
      research exposure for most medical students, and the summer between their first
      and second years of medical school is generally the longest period they can
      devote solely to research. The goal of short-term training programs is to whet
      the students' appetite for research and spark their interest in the field.
      Relatively little research has been done to test the effectiveness of short-term
      research training programs. In an effort to examine short-term effects of three
      different NIH-funded summer research training programs for medical students, we
      assessed the trainees' (N = 75) research self-efficacy prior to and after the
      programs using an 11-item scale. These hands-on training programs combined
      experiential, didactic, and mentoring elements. The students demonstrated a
      significant increase in their self-efficacy for research. Trainees' gender,
      ranking of their school, type of research, and specific content of research
      project did not predict improvement. Effect sizes for different types of items on
      the scale varied, with the largest gain seen in research methodology and
      communication of study findings. 

PMID- 24330696
TI  - Early career academic researchers and community-based participatory research:
      wrestling match or dancing partners?
AB  - Early career faculty members at academic medical centers face unique obstacles
      when engaging in community-based participatory research (CBPR). Challenges and
      opportunities for solutions pertaining to mentorship, time demands, unfamiliarity
      of colleagues with CBPR approaches, ethical review regulations, funding, and
      publication and promotion are discussed. 

PMID- 24330697
TI  - PCOR, CER, and CBPR: alphabet soup or complementary fields of health research?
AB  - Comparative effectiveness research (CER) and community- based participatory
      research (CBPR) are two fields of research that do not have a history of strong
      collaboration. However, CER and CBPR researchers could benefit from
      interdisciplinary collaboration to design and implement relevant, timely, action
      oriented research. This commentary explores field-specific definitions of
      stakeholders and then outlines various roles stakeholders might play within grant
      funded research. Questions such as "What stakeholders should be involved?" and
      "How are stakeholders involved?" are addressed. The goal of this commentary is to
      highlight how the expertise and experiences of CBPR investigators can enhance the
      field of CER and to describe strategies for encouraging stakeholder involvement
      in CER research through the lens of CBPR. It is recommended that a team-based
      approach to conducting stakeholder-engaged CER encourages multiple stakeholders
      and "end users" to contribute their diverse expertise to the research process and
      contributes to the development of research with an increased likelihood of
      improving patient health and healthcare. 

PMID- 24330699
TI  - Need for a research ethics remediation program.

PMID- 24330698
TI  - Pathways of translation: deep brain stimulation.
AB  - Electrical stimulation of the brain has a 2000 year history. Deep brain
      stimulation (DBS), one form of neurostimulation, is a functional neurosurgical
      approach in which a high-frequency electrical current stimulates targeted brain
      structures for therapeutic benefit. It is an effective treatment for certain
      neuropathologic movement disorders and an emerging therapy for psychiatric
      conditions and epilepsy. Its translational journey did not follow the typical
      bench-to-bedside path, but rather reversed the process. The shift from ancient
      and medieval folkloric remedy to accepted medical practice began with independent
      discoveries about electricity during the 19th century and was fostered by
      technological advances of the 20th. In this paper, we review that journey and
      discuss how the quest to expand its applications and improve outcomes is taking
      DBS from the bedside back to the bench. 

PMID- 24330701
TI  - Molecular and serological evidence for the circulation of the tick symbiont
      Midichloria (Rickettsiales: Midichloriaceae) in different mammalian species.
AB  - BACKGROUND: The Midichloriaceae is a novel family of the order Rickettsiales,
      that encompasses intracellular bacteria associated with hard ticks (Ixodidae) and
      other arthropods. The most intensively investigated member of this family is
      Midichloria mitochondrii, a symbiotic bacterium of the sheep tick Ixodes ricinus,
      characterized by the capacity of multiplying inside the mitochondria. A recent
      study suggested that these bacteria might be inoculated into the human host
      during the tick bite. The purpose of this study was to determine the potential
      infectivity of Midichloria bacteria for non-human animals exposed to the risk of
      tick bite. METHODS: Blood from horses, cattle, sheep and dogs exposed to the risk
      of tick bite was included in this study. DNAs were extracted, and amplified using
      16S ribosomal RNA primers conserved in the Midichloria genus. Furthermore, sera
      from dogs exposed to the risk of tick bite were analyzed in order to evaluate the
      presence of antibodies against the recombinant flagellar protein (rFliD) from M.
      mitochondrii using an ELISA test. RESULTS: Here we present two lines of evidence
      that support the possibility that bacteria from the genus Midichloria are
      inoculated into vertebrate hosts during a tick bite: (i) a direct evidence, i.e.
      the detection of circulating DNA from bacteria related with M. mitochondrii, in
      the blood of vertebrates exposed to tick parasitism; (ii) a further indirect
      evidence, i.e. the presence of antibodies against an antigen from M. mitochondrii
      in dogs exposed to the risk of tick bite. It is interesting to note that
      variability was detected in the Midichloria gene sequences recovered from
      positive animals, and that some of these sequences were identical to those
      generated from tick-associated Midichloria. CONCLUSIONS: Based on the results,
      and on the overall information so far published on the genus Midichloria, we
      suggest that these bacteria are likely to represent a novel group of vector-borne
      agents, with the potential of infecting mammalian hosts. Whether inoculation of
      Midichloria bacteria could cause a true infection and pathological alteration in
      mammalian hosts is still to be determined. Surely, results emphasize the
      relevance of Midichloria bacteria in investigations on tick immunology and tick
      bite markers.

PMID- 24330702
TI  - Bacterial contamination, bacterial profile and antimicrobial susceptibility
      pattern of isolates from stethoscopes at Jimma University Specialized Hospital.
AB  - INTRODUCTION: Hospital acquired infections are recognized as critical public
      health problems. Infections are frequently caused by organisms residing in
      healthcare environment, including contaminated medical equipment like
      Stethoscopes. OBJECTIVE: To determine bacterial contamination, bacterial profile
      and anti-microbial susceptibility pattern of the isolates from stethoscopes at
      Jimma University Specialized Hospital. METHODOLOGY: Cross-sectional study
      conducted from May to September 2011 at Jimma University Specialized Hospital.
      One hundred seventy-six stethoscopes owned by Health Care Workers (HCWs) and
      Medical students were randomly selected and studied. Self-administered structured
      questionnaire was used to collect socio-demographic data. Specimen was collected
      using moisten sterile cotton swab and 1 ml normal saline was used to transport
      the specimen, all laboratory investigations were done following standard
      microbiological techniques, at Microbiology Laboratory, Jimma University. SPSS
      windows version 16 used for data analysis and P <0.05 was considered
      statistically significant. RESULT: A total, of 151 (85.8%) stethoscopes were
      contaminated. A total of 256 bacterial strains and a mean of 1.44*104
      CFUs/diaphragm of stethoscopes was isolated. Of the 256 isolates, 133 (52%) were
      potential pathogens like S. aureus, Klebsiella spp., Citrobacter spp., Salmonella
      spp., Proteus spp., Enterobacter spp., P. aeruginosa and E. coli. All strains
      were resistant to multiple classes of antibiotics (two to eight classes of
      antibiotics). Disinfection practice was poor. Disinfection practice was found to
      be associated with bacterial contamination of stethoscopes (P < 0.05). High
      contamination rate 100 (90.9%) was observed among stethoscopes that had never
      been disinfected; while the least contamination 29 (72.2%) was found on those
      disinfected a week or less before the survey. CONCLUSION: Bacterial contamination
      of the stethoscope was significant. The isolates were potential pathogens and
      resistant to multiple classes of antibiotics. Stethoscope is potential vehicle in
      the transmission of infections between patients and Healthcare Workers.
      Stethoscope diaphragm should be disinfected before and after each patient
      contact.

PMID- 24330703
TI  - Appendiceal spirochaetosis in children.
AB  - BACKGROUND: Acute appendicitis is a surgical emergency in which the appendix is
      surgically removed to prevent peritonitis due to perforation of the appendix.
      Depending on age and gender, up to 17% of removed appendices do not show the
      histopathological changes pathognomonic for acute appendicitis and are called
      'pseudo-appendicitis'. Intestinal spirochaetes have been reported in up to 12.3%
      of these non-inflamed appendices obtained from adults. Although children carry
      the highest risk for acute appendicitis, not much is known on the prevalence of
      intestinal spirochaetes in children. The aim of this study was to determine
      whether there is an association between pseudo-appendicitis and appendiceal
      spirochaetosis in children. METHODS: Archival appendix specimens from paediatric
      patients (less than 18 years old) were obtained from two Dutch hospitals (acute
      appendicitis, n = 63; pseudo-appendicitis, n = 55; control appendices, n = 33)
      and microscopically analysed by H&E staining and spirochaete-specific
      immunohistochemistry and Brachyspira species specific real-time PCR. RESULTS:
      Five out of 142 appendices were found to be positive, all in male patients: one
      in the acute appendicitis group, two in the pseudo-appendicitis group and two in
      the control group. CONCLUSION: The results obtained do not provide evidence for a
      role of Brachyspira species infection in the aetiology of acute appendicitis in
      children.

PMID- 24330704
TI  - Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down
      regulation.
AB  - BACKGROUND: Breast cancer is a major health problem that threatens the lives of
      millions of women worldwide each year. Most of the chemotherapeutic agents that
      are currently used to treat this complex disease are highly toxic with long-term
      side effects. Therefore, novel generation of anti-cancer drugs with higher
      efficiency and specificity are urgently needed. METHODS: Breast cancer cell lines
      were treated with eugenol and cytotoxicity was measured using the WST-1 reagent,
      while propidium iodide/annexinV associated with flow cytometry was utilized in
      order to determine the induced cell death pathway. The effect of eugenol on
      apoptotic and pro-carcinogenic proteins, both in vitro and in tumor xenografts
      was assessed by immunoblotting. While RT-PCR was used to determine eugenol effect
      on the E2F1 and survivin mRNA levels. In addition, we tested the effect of
      eugenol on cell proliferation using the real-time cell electronic sensing system.
      RESULTS: Eugenol at low dose (2 MUM) has specific toxicity against different
      breast cancer cells. This killing effect was mediated mainly through inducing the
      internal apoptotic pathway and strong down-regulation of E2F1 and its downstream
      antiapoptosis target survivin, independently of the status of p53 and ERalpha.
      Eugenol inhibited also several other breast cancer related oncogenes, such as NF
      kappaB and cyclin D1. Moreover, eugenol up-regulated the versatile cyclin
      dependent kinase inhibitor p21WAF1 protein, and inhibited the proliferation of
      breast cancer cells in a p53-independent manner. Importantly, these anti
      proliferative and pro-apoptotic effects were also observed in vivo in xenografted
      human breast tumors. CONCLUSION: Eugenol exhibits anti-breast cancer properties
      both in vitro and in vivo, indicating that it could be used to consolidate the
      adjuvant treatment of breast cancer through targeting the E2F1/survivin pathway,
      especially for the less responsive triple-negative subtype of the disease.

PMID- 24330705
TI  - The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise
      performance.
AB  - Caffeine, nicotine, ethanol and tetrahydrocannabinol (THC) are among the most
      prevalent and culturally accepted drugs in western society. For example, in
      Europe and North America up to 90% of the adult population drinks coffee daily
      and, although less prevalent, the other drugs are also used extensively by the
      population. Smoked tobacco, excessive alcohol consumption and marijuana
      (cannabis) smoking are addictive and exhibit adverse health effects. These drugs
      are not only common in the general population, but have also made their way into
      elite sports because of their purported performance-altering potential. Only one
      of the drugs (i.e., caffeine) has enough scientific evidence indicating an
      ergogenic effect. There is some preliminary evidence for nicotine as an ergogenic
      aid, but further study is required; cannabis and alcohol can exhibit ergogenic
      potential under specific circumstances but are in general believed to be
      ergolytic for sports performance. These drugs are currently (THC, ethanol) or
      have been (caffeine) on the prohibited list of the World Anti-Doping Agency or
      are being monitored (nicotine) due to their potential ergogenic or ergolytic
      effects. The aim of this brief review is to evaluate the effects of caffeine,
      nicotine, ethanol and THC by: 1) examining evidence supporting the ergogenic or
      ergolytic effects; 2) providing an overview of the mechanism(s) of action and
      physiological effects; and 3) where appropriate, reviewing their impact as
      performance-altering aids used in recreational and elite sports. 

PMID- 24330706
TI  - Biomarkers and perfusion--training-induced changes after stroke (BAPTISe):
      protocol of an observational study accompanying a randomized controlled trial.
AB  - BACKGROUND: Physical activity is believed to exert a beneficial effect on
      functional and cognitive rehabilitation of patients with stroke. Although studies
      have addressed the impact of physical exercise in cerebrovascular prevention and
      rehabilitation, the underlying mechanisms leading to improvement are poorly
      understood. Training-induced increase of cerebral perfusion is a possible
      mediating mechanism. Our exploratory study aims to investigate training-induced
      changes in blood biomarker levels and magnetic resonance imaging in patients with
      subacute ischemic stroke. METHODS/DESIGN: This biomarker-driven study uses an
      observational design to examine a subgroup of patients in the randomized,
      controlled PHYS-STROKE trial. In PHYS-STROKE, 215 patients with subacute stroke
      (hemorrhagic and ischemic) receive either 4 weeks of physical training (aerobic
      training, 5 times a week, for 50 minutes) or 4 weeks of relaxation sessions (5
      times a week, for 50 minutes). A convenience sample of 100 of these patients with
      ischemic stroke will be included in BAPTISe and will receive magnetic resonance
      imaging (MRI) scans and an additional blood draw before and after the PHYS-STROKE
      intervention. Imaging scans will address parameters of cerebral perfusion, vessel
      size imaging, and microvessel density (the Q factor) to estimate the degree of
      neovascularization in the brain. Blood tests will determine several parameters of
      immunity, inflammation, endothelial function, and lipometabolism. Primary
      objective of this study is to evaluate differential changes in MRI and blood
      derived biomarkers between groups. Other endpoints are next cerebrovascular
      events and functional status of the patient after the intervention and after 3
      months assessed by functional scores, in particular walking speed and Barthel
      index (co-primary endpoints of PHYS-STROKE). Additionally, we will assess the
      association between functional outcomes and biomarkers including imaging results.
      For all endpoints we will compare changes between patients who received physical
      fitness training and patients who had relaxation sessions. DISCUSSION: This
      exploratory study will be the first to investigate the effects of physical
      fitness training in patients with ischemic stroke on MRI-based cerebral
      perfusion, pertinent blood biomarker levels, and functional outcome. The study
      may have an impact on current patient rehabilitation strategies and reveal
      important information about the roles of MRI and blood-derived biomarkers in
      ischemic stroke. TRIAL REGISTRATION: NCT01954797.

PMID- 24330707
TI  - Frovatriptan and rizatriptan economic EVAluation: the FREEVA study.
AB  - BACKGROUND: The present pharmacoeconomic study compared the direct and indirect
      costs of using frovatriptan versus rizatriptan in the acute treatment of
      migraine. METHODS: Data on the cost-efficacy of the two triptans were derived
      from a recently published Italian, multicenter, randomized, double-blind, cross
      over patient preference study, comparing frovatriptan versus rizatriptan. The
      direct costs were obtained by calculating the drug consumption, both of triptans
      and rescue medications. Prices of currently marketed drugs were obtained from
      Italian Drug Agency price list. The indirect costs were those related to
      absenteeism from the workplace due to migraine. RESULTS: 129 of the 148 patients
      with a current history of migraine randomized to the two study drugs and
      completing the study were analyzed. The number of attacks treated with only 1
      dose of study drug was higher with frovatriptan (157 vs. 147), whereas the number
      of attacks treated with >=2 doses of study medication was higher with rizatriptan
      (122 vs. 110 and 74 vs. 67, respectively). However, more patients treated with
      frovatriptan took a rescue medication (71 vs. 59). The total direct cost per
      attack (including study drug rescue medication) was 9.12 ? for frovatriptan and
      13.54 ? for rizatriptan (p < 0.05 between-treatments). As for indirect costs, in
      the group of patients treated with frovatriptan the mean number of lost working
      hours was significantly (p < 0.05) lower (1.5 h) compared to the subjects who
      used rizatriptan (2.8 h). Based on the earned income per unit of work, indirect
      costs per attack resulted to be 24.55 ? for frovatriptan and 45.84 ? for
      rizatriptan. Overall, the total costs, including direct and indirect costs, were
      evaluated to be 33.67 ? for frovatriptan and 59.38 ? for rizatriptan,
      respectively. CONCLUSIONS: Within the limitations of this model analysis,
      frovatriptan was found to be significantly more cost-effective than rizatriptan.
      This outcome can be explained by the lower acquisition cost of frovatriptan, the
      need for fewer doses, and the loss of fewer working hours. This finding could
      drive selection of the most appropriate oral treatment for acute migraine attacks
      based on both individual patient's needs and the cost-effectiveness of the
      available drugs. TRIAL REGISTRATION: 2006-002572-17 (EudraCT).

PMID- 24330708
TI  - Beliefs and attitudes about breast cancer and screening practices among Arab
      women living in Qatar: a cross-sectional study.
AB  - BACKGROUND: Despite rising breast cancer incidence and mortality rates, breast
      cancer screening (BCS) rates among women in Qatar remain low. Previous studies
      indicate the need to better understand the many complex beliefs, values, and
      attitudes that influence Arab women's health seeking behavior for the development
      of culturally appropriate and effective intervention strategies to address breast
      cancer in the Middle East. This study investigates beliefs, attitudes, and BCS
      practices of Arabic-speaking women in Qatar. METHODS: A multicenter, cross
      sectional quantitative survey of 1,063 (87.5% response rate) Arabic-speaking
      female Qatari citizens and non-Qatari residents, 35 years of age or older, was
      conducted in Qatar from March 2011 to July 2011. Associations between beliefs and
      BCS practice were estimated using chi-square tests and multivariate logistic
      regression analyses. Participants who adhered to BCS guidelines (BCS practice =
      Yes) were compared to those who did not (BCS practice = No). RESULTS: In addition
      to low levels of awareness and low participation rates in BCS, one quarter of the
      participants stated their doctors talked to them about breast cancer, and less
      than half of the women interviewed believed breast cancer can be prevented. Women
      who engaged in BCS practice were more likely to have a doctor who talked to them
      about breast cancer, to believe they were in good-excellent health, that cancer
      can be prevented, or that cancer might be hereditary. The majority wanted to know
      if they had cancer and felt their health care needs were being met. The main
      reasons given for not planning BCS were lack of a doctor's recommendation, fear,
      and embarrassment. CONCLUSIONS: These findings indicate that a variety of
      channels (health care providers, media, breast cancer survivors, community
      leaders) should be utilized to create culturally appropriate breast cancer
      intervention programs and increased awareness of breast cancer, BCS, and the
      benefits of early detection of breast cancer. Employment of these measures will
      reduce breast cancer mortality rates among Arabic-speaking women living in the
      State of Qatar.

PMID- 24330711
TI  - Correction: Characteristics of the elderly who do not visit primary care
      physicians.

PMID- 24330710
TI  - The cell-to-cell coordination between activated T cells and CpG-stimulated
      macrophages synergistically induce elevated levels of IL-10 via NF-kappaB1,
      STAT3, and CD40/CD154.
AB  - BACKGROUND: Studies into the regulation of interleukin-10 (IL-10), have focused
      only on the molecular or single-cell level. The cues that induce IL-10 in the
      context of cell-to-cell communication are scarce. To fill this gap, this study
      elucidates the cell-to-cell interaction dependent regulation of IL-10. RESULTS:
      The simultaneous activation of CD4+ T cells via CD3/CD28 and stimulation of
      macrophages via CpG and their intercellular communication with each other in the
      same microenvironment is necessary to induce a synergistic expression of IL-10.
      NF-kappaB1, ERK, and STAT3 are positive regulators of this cell-to-cell
      communication mediated molecular change of IL-10 induction. Strikingly, the
      activation of CD40/CD154 signaling is a negative regulator of IL-10 levels by
      CD3/CD28/CpG. CONCLUSIONS: These findings are of prominence as CD3/CD28/CpG
      treatment can induce the anti-inflammatory cytokines IL-10 and IL-30, and the
      activation or inhibition of the CD40/CD154 acts as molecular rheostat of the
      expression of IL-10 or IL-30. More importantly, this not only serves as an
      example of IL-10 regulation at the cellular via coordination of two signals from
      two cell types, but these findings also lay the molecular and cellular groundwork
      for future studies to investigate how to manipulate IL-10 or IL-30 production
      during inflammation, cancer, or autoimmune diseases.

PMID- 24330709
TI  - Education of research ethics for clinical investigators with Moodle tool.
AB  - BACKGROUND: In clinical research scientific, legal as well as ethical aspects are
      important. It is well known that clinical investigators at university hospitals
      have to undertake their PhD-studies alongside their daily work and reconciling
      work and study can be challenging. The aim of this project was to create a web
      based course in clinical research bioethics (5 credits) and to examine whether
      the method is suitable for teaching bioethics. The course comprised of six
      modules: an initial examination (to assess knowledge in bioethics), information
      on research legislation, obtaining permissions from authorities, writing an essay
      on research ethics, preparing one's own study protocol, and a final exam. All
      assignments were designed with an idea of supporting students to reflect on their
      learning with their own research. METHODS: 57 PhD-students (medical, nursing and
      dental sciences) enrolled and 46 completed the course. Course evaluation was done
      using a questionnaire. The response rate was 78%. Data were analyzed using
      quantitative methods and qualitative content analysis. RESULTS: The course was
      viewed as useful and technically easy to perform. Students were pleased with the
      guidance offered. Personal feedback from teachers about students' own performance
      was seen advantageous and helped them to appreciate how these aspects could be
      applied their own studies. The course was also considered valuable for future
      research projects. CONCLUSIONS: Ethical issues and legislation of clinical
      research can be understood more easily when students can reflect the principles
      upon their own research project. Web based teaching environment is a feasible
      learning method for clinical investigators.

PMID- 24330713
TI  - Cutaneous and pulmonary sarcoidosis following treatment of multiple sclerosis
      with interferon-beta-1b: a case report.
AB  - INTRODUCTION: Several cases of sarcoidosis following treatment with interferon
      alpha have been reported in the literature, but those following interferon-beta
      are very rare. We report the case of a patient with multiple sclerosis who
      developed pulmonary and cutaneous sarcoidosis following treatment with
      Betaseron(r) (interferon-beta-1b). CASE PRESENTATION: A 33-year-old Caucasian
      woman with a history of multiple sclerosis, treated with interferon-beta-1b for
      2.5 years developed erythema nodosum in her lower limbs, a breast abscess, and
      unilateral adenopathy of her left lung. A skin biopsy confirmed sarcoidosis.
      After the discontinuation of interferon-beta-1b and treatment with indomethacin
      and prednisolone, she recovered. CONCLUSIONS: Sarcoidosis is considered one of
      the most common multiple sclerosis imitators with involvement of the central
      nervous system. However, although rare, sarcoidosis can develop following
      treatment with interferon-beta-1b and should be considered in patients with
      multiple sclerosis treated with beta-interferons who develop pulmonary or extra
      pulmonary manifestations of sarcoidosis. Interferon-beta-1b discontinuation is
      the first and most important step in the treatment of such cases followed by
      treatment with corticosteroids.

PMID- 24330712
TI  - Genome-wide characterization of microRNA in foxtail millet (Setaria italica).
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding, endogenous RNAs
      that play key roles in many biological processes in both animals and plants.
      Although many miRNAs have been identified in a large number of organisms, the
      miRNAs in foxtail millet (Setaria italica) have, until now, been poorly
      understood. RESULTS: In this study, two replicate small RNA libraries from
      foxtail millet shoots were sequenced, and 40 million reads representing over 10
      million unique sequences were generated. We identified 43 known miRNAs, 172 novel
      miRNAs and 2 mirtron precursor candidates in foxtail millet. Some miRNA*s of the
      known and novel miRNAs were detected as well. Further, eight novel miRNAs were
      validated by stem-loop RT-PCR. Potential targets of the foxtail millet miRNAs
      were predicted based on our strict criteria. Of the predicted target genes, 79%
      (351) had functional annotations in InterPro and GO analyses, indicating the
      targets of the miRNAs were involved in a wide range of regulatory functions and
      some specific biological processes. A total of 69 pairs of syntenic miRNA
      precursors that were conserved between foxtail millet and sorghum were found.
      Additionally, stem-loop RT-PCR was conducted to confirm the tissue-specific
      expression of some miRNAs in the four tissues identified by deep-sequencing.
      CONCLUSIONS: We predicted, for the first time, 215 miRNAs and 447 miRNA targets
      in foxtail millet at a genome-wide level. The precursors, expression levels,
      miRNA* sequences, target functions, conservation, and evolution of miRNAs we
      identified were investigated. Some of the novel foxtail millet miRNAs and miRNA
      targets were validated experimentally.

PMID- 24330714
TI  - Association between haptoglobin and IgM levels and the clinical progression of
      caseous lymphadenitis in sheep.
AB  - BACKGROUND: Sheep caseous lymphadenitis (CLA), caused by Corynebacterium
      pseudotuberculosis (Cp), is associated with direct economic losses and presents
      significant zoonotic potential. Despite the importance of the disease, a
      satisfactory vaccine model has not been developed. Thus, this study aimed to
      investigate the association between haptoglobin (Hp) and IgM levels and the
      clinical progression of CLA in primarily infected sheep and in sheep immunized
      with Cp- secreted antigens adjuvanted with Quillaja saponaria saponins. These
      animals were kept with CLA-positive sheep to simulate natural exposure that
      occurs in field conditions. During the experiment, the Hp and IgM levels were
      monitored for 21 days, and the development of internal CLA lesions was
      investigated through necropsies on day182 post-immunization. RESULTS: Primarily
      infected sheep in Group 2 (inoculated with 2x105 Cp virulent strain) had higher
      Hp values between the first and ninth days post inoculation (PI) than sheep in
      Group 1 (control; P < 0.05). Immunized animals in Group 3 had significantly
      higher Hp values between the third and seventh days PI, compared with the control
      group (P < 0.01). Binary logistic regression (BLR) analysis of primarily infected
      sheep indicated an association between Hp concentration and CLA clinical
      progression: animals with high Hp values had 99.9% less risk of having CLA
      abscesses than animals with low Hp levels (Odds ratio = 0.001, P < 0.05). Both
      experimental groups had significantly higher IgM titers than the control group
      around the ninth and eleventh days PI (P < 0.05). The BLR analysis for immunized
      sheep indicated an association between IgM levels and clinical progression: sheep
      with high IgM titers had 100.0% less risk of having CLA abscesses than animals
      with low IgM levels (Odds ratio = 0.000, P < 0.05). CONCLUSIONS: Resistance to C.
      pseudotuberculosis infection is supported by the early acute phase response, in
      which up-regulation of Hp and IgM were predictive of a lower risk of CLA lesion
      development. Because the immunogen used in this study induced a high production
      of both Hp and IgM, Q. saponaria saponin should be considered a promising
      candidate in vaccine formulations against sheep CLA.

PMID- 24330715
TI  - Smoking among older childbearing women - a marker of risky health behaviour a
      registry-based study in Finland.
AB  - BACKGROUND: Smoking during pregnancy is known to negatively affect pregnancy
      outcomes and it has been associated with numerous complications during pregnancy.
      Smoking is more common in younger pregnant women, but previous research has shown
      that adverse pregnancy outcomes related to older maternal age and smoking are
      even more harmful than with younger smokers. The aim of this study was to compare
      pregnancy outcomes among smoking and non-smoking pregnant women aged <35 years
      and >=35 years. METHODS: In this registry-based study, the data were collected
      from three national Finnish health registries: Finnish Medical Birth Register,
      Finnish Hospital Discharge Register, and Register of Congenital Malformations
      between the years 1997 and 2008. The data included information on 80 260 women
      who were smoking during pregnancy, of which 11 277 (9%) were >=35 years and 68
      983 (13%) were <35 years old. In multivariate modelling, the main outcome
      measures were preterm delivery, low Apgar scores at 1 min., low birth weight,
      small for gestational age, fetal death and preeclampsia. RESULTS: Fewer older
      women smoked during pregnancy (9%) than younger women did (13%). Smoking
      increased the risk of adverse pregnancy outcomes, most in the older group.
      Multivariate logistic regression using non-smoking women aged <35 years as a
      reference group indicated that smoking women <35 years had higher rates of
      preterm delivery (OR 1.27 CI 1.20-1.35), SGA (OR 2.18 CI 2.10-2.26) and LBW (OR
      1.73 CI 1.62-1.84).Non-smoking women >=35 had higher rates of preterm delivery
      (OR 1.15 CI 1.10-1.20), fetal death (OR 1.36 CI 1.12-1.64), preeclampsia (OR 1.14
      CI 1.09-1.20) and LBW (OR 1.13 CI 1.07-1.19).Smoking women >=35 had higher rates
      of preterm delivery (OR 1.60 CI 1.40-1.82), SGA (OR 2.55 CI 2.34-2.79), fetal
      death (OR 2.70 CI 1.80-4.05) and LBW (OR 2.50 CI 2.20-2.80). CONCLUSIONS: Smoking
      during pregnancy increased the risk of adverse pregnancy outcomes in all women,
      but the rates were the highest for women aged >=35 years. Pregnant women aged
      >=35 years smoking during pregnancy was a distinctly high risk group. Maternity
      care should identify these women and support them in cessation of smoking during
      the first trimester of pregnancy.

PMID- 24330716
TI  - A nanobody targeting the F-actin capping protein CapG restrains breast cancer
      metastasis.
AB  - INTRODUCTION: Aberrant turnover of the actin cytoskeleton is intimately
      associated with cancer cell migration and invasion. Frequently however, evidence
      is circumstantial, and a reliable assessment of the therapeutic significance of a
      gene product is offset by lack of inhibitors that target biologic properties of a
      protein, as most conventional drugs do, instead of the corresponding gene.
      Proteomic studies have demonstrated overexpression of CapG, a constituent of the
      actin cytoskeleton, in breast cancer. Indirect evidence suggests that CapG is
      involved in tumor cell dissemination and metastasis. In this study, we used llama
      derived CapG single-domain antibodies or nanobodies in a breast cancer metastasis
      model to address whether inhibition of CapG activity holds therapeutic merit.
      METHODS: We raised single-domain antibodies (nanobodies) against human CapG and
      used these as intrabodies (immunomodulation) after lentiviral transduction of
      breast cancer cells. Functional characterization of nanobodies was performed to
      identify which biochemical properties of CapG are perturbed. Orthotopic and tail
      vein in vivo models of metastasis in nude mice were used to assess cancer cell
      spreading. RESULTS: With G-actin and F-actin binding assays, we identified a CapG
      nanobody that binds with nanomolar affinity to the first CapG domain.
      Consequently, CapG interaction with actin monomers or actin filaments is blocked.
      Intracellular delocalization experiments demonstrated that the nanobody interacts
      with CapG in the cytoplasmic environment. Expression of the nanobody in breast
      cancer cells restrained cell migration and Matrigel invasion. Notably, the
      nanobody prevented formation of lung metastatic lesions in orthotopic xenograft
      and tail-vein models of metastasis in immunodeficient mice. We showed that CapG
      nanobodies can be delivered into cancer cells by using bacteria harboring a type
      III protein secretion system (T3SS). CONCLUSIONS: CapG inhibition strongly
      reduces breast cancer metastasis. A nanobody-based approach offers a fast track
      for gauging the therapeutic merit of drug targets. Mapping of the nanobody-CapG
      interface may provide a platform for rational design of pharmacologic compounds.

PMID- 24330717
TI  - Epigenetic silencing of glutaminase 2 in human liver and colon cancers.
AB  - BACKGROUND: Glutaminase 2 (Gls2) is a p53 target gene and is known to play an
      important role in energy metabolism. Gls2 has been reported to be downregulated
      in human hepatocellular carcinomas (HCC). However, the underlying mechanism
      responsible for its downregulation is still unclear. Here, we investigated Gls2
      expression and its promoter methylation status in human liver and colon cancers.
      METHODS: mRNA expression of Gls2 was determined in human liver and colon cancer
      cell lines and HCC tissues by real-time PCR and promoter methylation was analyzed
      by methylation-specific PCR (MSP) and validated by bisulfite genome sequencing
      (BGS). Cell growth was determined by colony formation assay and MTS assay.
      Statistical analysis was performed by Wilcoxon matched-pairs test or non
      parametric t test. RESULTS: First, we observed reduced Gls2 mRNA level in a
      selected group of liver and colon cancer cell lines and in the cancerous tissues
      from 20 HCC and 5 human colon cancer patients in comparison to their non
      cancerous counter parts. Importantly, the lower level of Gls2 in cancer cells was
      closely correlated to its promoter hypermethylation; and chemical demethylation
      treatment with 5-aza-2'-deoxycytidine (Aza) increased Gls2 mRNA level in both
      liver and colon cancer cells, indicating that direct epigenetic silencing
      suppressed Gls2 expression by methylation. Next, we further examined this
      correlation in human HCC tissues, and 60% of primary liver tumor tissues had
      higher DNA methylation levels when compared with adjacent non-tumor tissues.
      Detailed methylation analysis of 23 CpG sites at a 300-bp promoter region by
      bisulfite genomic sequencing confirmed its methylation. Finally, we examined the
      biological function of Gls2 and found that restoring Gls2 expression in cancer
      cells significantly inhibited cancer cell growth and colony formation ability
      through induction of cell cycle arrest. CONCLUSIONS: We provide evidence showing
      that epigenetic silencing of Gls2 via promoter hypermethylation is common in
      human liver and colon cancers and Gls2 appears to be a functional tumor
      suppressor involved in the liver and colon tumorigenesis.

PMID- 24330718
TI  - Virulence characteristics of five new Campylobacter jejuni chicken isolates.
AB  - Campylobacter enteritis has emerged as one of the most common forms of human
      diarrheal illness. In this study we have investigated the virulence potential of
      five new C. jejuni chicken isolates (RO14, RO19, RO24, RO29 and RO37) originated
      from private households in the rural regions of Banat and Transylvania in
      Romania. Following isolation and in vitro virulence assay, on HCT-8 cells, our
      results show that all the C. jejuni chicken isolates overcome the virulence
      abilities of the highly virulent strain C. jejuni 81-176. Motility, an important
      virulence factor was significantly improved in all the new chicken isolates. The
      ability to survive to the antimicrobial activity of the human serum, to resist to
      the violent attack of bile acids and to survive in the presence of synthetic
      antibiotics was increased in all the chicken isolates. However, these were
      statistically significant only for isolates RO29 and RO37. In conclusion our
      study shows, based on invasiveness and motility, and also on the data provided by
      the serum and bile resistance experiments that all the new chicken isolates are
      able to infect human cells, in vitro, and could potentially represent a health
      hazard for humans. 

PMID- 24330719
TI  - Diesel exhaust particulate increases the size and complexity of lesions in
      atherosclerotic mice.
AB  - OBJECTIVE: Diesel exhaust particulate (DEP), a major component of urban air
      pollution, has been linked to atherogenesis and precipitation of myocardial
      infarction. We hypothesized that DEP exposure would increase and destabilise
      atherosclerotic lesions in apolipoprotein E deficient (ApoE-/-) mice. METHODS:
      ApoE-/- mice were fed a 'Western diet' (8 weeks) to induce 'complex'
      atherosclerotic plaques, with parallel experiments in normal chow fed wild-type
      mice. During the last 4 weeks of feeding, mice received twice weekly instillation
      (oropharyngeal aspiration) of 35 MUL DEP (1 mg/mL, SRM-2975) or vehicle (saline).
      Atherosclerotic burden was assessed by en-face staining of the thoracic aorta and
      histological examination of the brachiocephalic artery. RESULTS: Brachiocephalic
      atherosclerotic plaques were larger in ApoE-/- mice treated with DEP (59 +/- 10%)
      than in controls (32 +/- 7%; P = 0.017). In addition, DEP-treated mice had more
      plaques per section of artery (2.4 +/- 0.2 vs 1.8 +/- 0.2; P = 0.048) and buried
      fibrous layers (1.2 +/- 0.2 vs 0.4 +/- 0.1; P = 0.028). These changes were
      associated with lung inflammation and increased antioxidant gene expression in
      the liver, but not with changes in endothelial function, plasma lipids or
      systemic inflammation. CONCLUSIONS: Increased atherosclerosis is caused by the
      particulate component of diesel exhaust producing advanced plaques with a
      potentially more vulnerable phenotype. These results are consistent with the
      suggestion that removal of the particulate component would reduce the adverse
      cardiovascular effects of diesel exhaust.

PMID- 24330720
TI  - Modelling adult Aedes aegypti and Aedes albopictus survival at different
      temperatures in laboratory and field settings.
AB  - BACKGROUND: The survival of adult female Aedes mosquitoes is a critical component
      of their ability to transmit pathogens such as dengue viruses. One of the
      principal determinants of Aedes survival is temperature, which has been
      associated with seasonal changes in Aedes populations and limits their
      geographical distribution. The effects of temperature and other sources of
      mortality have been studied in the field, often via mark-release-recapture
      experiments, and under controlled conditions in the laboratory. Survival results
      differ and reconciling predictions between the two settings has been hindered by
      variable measurements from different experimental protocols, lack of precision in
      measuring survival of free-ranging mosquitoes, and uncertainty about the role of
      age-dependent mortality in the field. METHODS: Here we apply generalised additive
      models to data from 351 published adult Ae. aegypti and Ae. albopictus survival
      experiments in the laboratory to create survival models for each species across
      their range of viable temperatures. These models are then adjusted to estimate
      survival at different temperatures in the field using data from 59 Ae. aegypti
      and Ae. albopictus field survivorship experiments. The uncertainty at each stage
      of the modelling process is propagated through to provide confidence intervals
      around our predictions. RESULTS: Our results indicate that adult Ae. albopictus
      has higher survival than Ae. aegypti in the laboratory and field, however, Ae.
      aegypti can tolerate a wider range of temperatures. A full breakdown of survival
      by age and temperature is given for both species. The differences between
      laboratory and field models also give insight into the relative contributions to
      mortality from temperature, other environmental factors, and senescence and over
      what ranges these factors can be important. CONCLUSIONS: Our results support the
      importance of producing site-specific mosquito survival estimates. By including
      fluctuating temperature regimes, our models provide insight into seasonal
      patterns of Ae. aegypti and Ae. albopictus population dynamics that may be
      relevant to seasonal changes in dengue virus transmission. Our models can be
      integrated with Aedes and dengue modelling efforts to guide and evaluate vector
      control, better map the distribution of disease and produce early warning systems
      for dengue epidemics.

PMID- 24330721
TI  - Using simple agent-based modeling to inform and enhance neighborhood walkability.
AB  - BACKGROUND: Pedestrian-friendly neighborhoods with proximal destinations and
      services encourage walking and decrease car dependence, thereby contributing to
      more active and healthier communities. Proximity to key destinations and services
      is an important aspect of the urban design decision making process, particularly
      in areas adopting a transit-oriented development (TOD) approach to urban
      planning, whereby densification occurs within walking distance of transit nodes.
      Modeling destination access within neighborhoods has been limited to circular
      catchment buffers or more sophisticated network-buffers generated using
      geoprocessing routines within geographical information systems (GIS). Both
      circular and network-buffer catchment methods are problematic. Circular catchment
      models do not account for street networks, thus do not allow exploratory 'what
      if' scenario modeling; and network-buffering functionality typically exists
      within proprietary GIS software, which can be costly and requires a high level of
      expertise to operate. METHODS: This study sought to overcome these limitations by
      developing an open-source simple agent-based walkable catchment tool that can be
      used by researchers, urban designers, planners, and policy makers to test
      scenarios for improving neighborhood walkable catchments. A simplified version of
      an agent-based model was ported to a vector-based open source GIS web tool using
      data derived from the Australian Urban Research Infrastructure Network (AURIN).
      The tool was developed and tested with end-user stakeholder working group input.
      RESULTS: The resulting model has proven to be effective and flexible, allowing
      stakeholders to assess and optimize the walkability of neighborhood catchments
      around actual or potential nodes of interest (e.g., schools, public transport
      stops). Users can derive a range of metrics to compare different scenarios
      modeled. These include: catchment area versus circular buffer ratios; mean number
      of streets crossed; and modeling of different walking speeds and wait time at
      intersections. CONCLUSIONS: The tool has the capacity to influence planning and
      public health advocacy and practice, and by using open-access source software, it
      is available for use locally and internationally. There is also scope to extend
      this version of the tool from a simple to a complex model, which includes agents
      (i.e., simulated pedestrians) 'learning' and incorporating other environmental
      attributes that enhance walkability (e.g., residential density, mixed land use,
      traffic volume).

PMID- 24330722
TI  - Neuropsychopathological comorbidities in learning disorders.
AB  - BACKGROUND: Learning Disorders (LD) are complex diseases that affect about 2-10%
      of the school-age population. We performed neuropsychological and
      psychopathological evaluation, in order to investigate comorbidity in children
      with LD. METHODS: Our sample consisted of 448 patients from 7 to 16 years of age
      with a diagnosis of LD, divided in two subgroups: Specific Learning Disorders
      (SLD), including reading, writing, mathematics disorders, and Learning Disorders
      Not Otherwise Specified (LD NOS). RESULTS: Comorbidity with
      neuropsychopathologies was found in 62.2% of the total sample. In the LSD
      subgroup, ADHD was present in 33%, Anxiety Disorder in 28.8%, Developmental
      Coordination Disorder in 17.8%, Language Disorder in 11% and Mood Disorder in
      9.4% of patients. In LD NOS subgroup, Language Disorder was present in 28.6%,
      Developmental Coordination Disorder in 27.5%, ADHD in 25.4%, Anxiety Disorder in
      16.4%, Mood Disorder in 2.1% of patients. A statistically significant presence
      was respectively found for Language and Developmental Coordination Disorder
      comorbidity in LD NOS and for ADHD, mood and anxiety disorder comorbidity in SLD
      subgroup. CONCLUSIONS: The different findings emerging in this study suggested to
      promote further investigations to better define the difference between SLD and LD
      NOS, in order to improve specific interventions to reduce the long range
      consequences.

PMID- 24330723
TI  - Migraine misdiagnosis as a sinusitis, a delay that can last for many years.
AB  - BACKGROUND: Sinusitis is the most frequent misdiagnosis given to patients with
      migraine.Therefore we decided to estimate the frequency of misdiagnosis of
      sinusitis among migraine patients. METHODS: The study included migraine patients
      with a past history of sinusitis. All included cases fulfilled the International
      Classification of Headache Disorders, 3rd edition (ICHD-III- beta) criteria. We
      excluded patients with evidence of sinusitis within the past 6 months of
      evaluation. Demographic data, headache history, medical consultation, and
      medication intake for headache and effectiveness of therapy before and after
      diagnosis were collected. RESULTS: A total of 130 migraine patients were
      recruited. Of these patients 106 (81.5%) were misdiagnosed as sinusitis. The mean
      time delay of migraine diagnosis was (7.75 +/- 6.29, range 1 to 38 years).
      Chronic migraine was significantly higher (p < 0.02) in misdiagnosed patients
      than in patients with proper diagnosis. Medication overuse headache (MOH) was
      reported only in patients misdiagnosed as sinusitis. The misdiagnosed patients
      were treated either medically 87.7%, or surgically12.3% without relieve of their
      symptoms in 84.9% and 76.9% respectively. However, migraine headache improved in
      68.9% after proper diagnosis and treatment. CONCLUSIONS: Many migraine patients
      were misdiagnosed as sinusitis. Strict adherence to the diagnostic criteria will
      prevent the delay in migraine diagnosis and help to prevent chronification of the
      headache and possible MOH.

PMID- 24330724
TI  - Agreement of self-reported physician diagnosis of migraine with international
      classification of headache disorders-II migraine diagnostic criteria in a cross
      sectional study of pregnant women.
AB  - BACKGROUND: Migraine, a common chronic-intermittent disorder among reproductive
      age women, has emerged as a novel risk factor for adverse perinatal outcomes.
      Diagnostic reliability of self-report of physician-diagnosed migraine has not
      been investigated in pregnancy cohort studies. We investigated agreement of self
      report of physician-diagnosed migraine with the diagnostic criteria promoted by
      the International Classification of Headache Disorders, 2nd edition (ICHD-II).
      METHODS: The cross-sectional study was conducted among 500 women who provided
      information on a detailed migraine questionnaire that allowed us to apply all
      ICHD-II diagnostic criteria. RESULTS: Approximately 92% of women reporting a
      diagnosis of migraine had the diagnosis between the ages of 11 and 40 years (<10
      years 6.8%; 11-20 years 38.8%; 21-30 years 42.7%; 31-40 years 10.7%; and >40
      years 1.0%). We confirmed self-reported migraine in 81.6% of women when applying
      the ICHD-II criteria for definitive migraine (63.1%) and probable migraine
      (18.5%). CONCLUSION: There is good agreement between self-reported migraine and
      ICHD-II-based migraine classification in this pregnancy cohort. We demonstrate
      the feasibility of using questionnaire-based migraine assessment according to
      full ICHD-II criteria in epidemiological studies of pregnant women.

PMID- 24330726
TI  - An unusual cause of shoulder pain in an elderly woman: a case report.
AB  - INTRODUCTION: Stress fracture of the clavicle is a rare entity. It can manifest
      itself with an atypical shoulder pain. The clavicle is vulnerable to pathological
      fractures from several causes such as neoplasm, infection and rarely metabolic
      bone disease. CASE PRESENTATION: We report a case of a bone insufficiency
      fracture of the clavicle, in a 67-year-old Moroccan woman patient with several
      risk factors of bone insufficiency including osteoporosis, osteomalacia and
      primary hyperparathyroidism. CONCLUSION: The diagnosis of bone insufficiency
      related fracture of the clavicle can be challenging. It should be considered in
      the differential diagnosis of shoulder or clavicle pain.

PMID- 24330725
TI  - Ups and downs of a transcriptional landscape shape iron deficiency associated
      chlorosis of the maize inbreds B73 and Mo17.
AB  - BACKGROUND: Improving nutrient homeostasis is a major challenge of a sustainable
      maize cultivation, and cornerstone to ensure food supply for a growing world
      population. Although, iron constitutes an important nutrient, iron availability
      is limited. In this respect, iron deficiency associated chlorosis causes severe
      yield losses every year. Natural variation of the latter trait has yet not been
      addressed in maize and was therefore studied in the present analysis. RESULTS: In
      this study, we i) report about the contrasting chlorosis phenotypes of the
      inbreds B73 and Mo17 at 10 and 300 MUM iron regime, ii) identified over 400
      significantly regulated transcripts (FDR < 0.05) within both inbreds at these
      growth conditions by deep RNA-Sequencing, iii) linked the gained knowledge with
      QTL information about iron deficiency related traits within the maize intermated
      B73 by Mo17 (IBM) population, and iv) highlighted contributing molecular
      pathways. In this respect, several genes within methionine salvage pathway and
      phytosiderophore synthesis were found to present constitutively high expression
      in Mo17, even under sufficient iron supply. Moreover, the same expression pattern
      could be observed for two putative bHLH transcription factors. In addition, a
      number of differentially expressed genes showed a co-localisation with QTL
      confidence intervals for iron deficiency related traits within the IBM
      population. CONCLUSIONS: Our study highlights differential iron deficiency
      associated chlorosis between B73 and Mo17 and represents a valuable resource for
      differentially expressed genes upon iron limitation and chlorosis response.
      Besides identifying two putative bHLH transcription factors, we propose that
      methionine salvage pathway and sterol metabolism amongst others; underlie the
      contrasting iron deficiency related chlorosis phenotype of both inbreds.
      Altogether, this study emphasizes a contribution of selected genes and pathways
      on natural trait variation within the IBM population.

PMID- 24330727
TI  - Interleukin-1beta sequesters hypoxia inducible factor 2alpha to the primary
      cilium.
AB  - BACKGROUND: The primary cilium coordinates signalling in development, health and
      disease. Previously we have shown that the cilium is essential for the anabolic
      response to loading and the inflammatory response to interleukin-1beta (IL
      1beta). We have also shown the primary cilium elongates in response to IL-1beta
      exposure. Both anabolic phenotype and inflammatory pathology are proposed to be
      dependent on hypoxia-inducible factor 2 alpha (HIF-2alpha). The present study
      tests the hypothesis that an association exists between the primary cilium and
      HIFs in inflammatory signalling. RESULTS: Here we show, in articular
      chondrocytes, that IL-1beta-induces primary cilia elongation with alterations to
      cilia trafficking of arl13b. This elongation is associated with a transient
      increase in HIF-2alpha expression and accumulation in the primary cilium. Prolyl
      hydroxylase inhibition results in primary cilia elongation also associated with
      accumulation of HIF-2alpha in the ciliary base and axoneme. This recruitment and
      the associated cilia elongation is not inhibited by blockade of HIFalpha
      transcription activity or rescue of basal HIF-2alpha expression. Hypomorphic
      mutation to intraflagellar transport protein IFT88 results in limited
      ciliogenesis. This is associated with increased HIF-2alpha expression and
      inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings
      suggest that ciliary sequestration of HIF-2alpha provides negative regulation of
      HIF-2alpha expression and potentially activity. This study indicates, for the
      first time, that the primary cilium regulates HIF signalling during inflammation.

PMID- 24330730
TI  - Is retirement good for your health? A systematic review of longitudinal studies.
AB  - BACKGROUND: Several studies regarding the effect of retirement on physical as
      well as mental health have been performed, but the results thereof remain
      inconclusive. The aim of this review is to systematically summarise the
      literature on the health effects of retirement, describing differences in terms
      of voluntary, involuntary and regulatory retirement and between blue-collar and
      white-collar workers. METHODS: A search for longitudinal studies using keywords
      that referred to the exposure (retirement), outcome (health-related) and study
      design (longitudinal) was performed using several electronic databases. Articles
      were then selected for full text analysis and the reference lists of the selected
      studies were checked for relevant studies. The quality of the studies was rated
      based on predefined criteria. Data was analysed qualitatively by using a best
      evidence synthesis. When possible, pooled mean differences and effect sizes were
      calculated to estimate the effect of retirement on health. RESULTS: Twenty-two
      longitudinal studies were included, of which eleven were deemed to be of high
      quality. Strong evidence was found for retirement having a beneficial effect on
      mental health, and contradictory evidence was found for retirement having an
      effect on perceived general health and physical health. Few studies examined the
      differences between blue- and white-collar workers and between voluntary,
      involuntary and regulatory retirement with regards to the effect of retirement on
      health outcomes. CONCLUSIONS: More longitudinal research on the health effects of
      retirement is needed, including research into potentially influencing factors
      such as work characteristics and the characteristics of retirement.

PMID- 24330729
TI  - Promoting state health department evidence-based cancer and chronic disease
      prevention: a multi-phase dissemination study with a cluster randomized trial
      component.
AB  - BACKGROUND: Cancer and other chronic diseases reduce quality and length of life
      and productivity, and represent a significant financial burden to society.
      Evidence-based public health approaches to prevent cancer and other chronic
      diseases have been identified in recent decades and have the potential for high
      impact. Yet, barriers to implement prevention approaches persist as a result of
      multiple factors including lack of organizational support, limited resources,
      competing emerging priorities and crises, and limited skill among the public
      health workforce. The purpose of this study is to learn how best to promote the
      adoption of evidence based public health practice related to chronic disease
      prevention. METHODS/DESIGN: This paper describes the methods for a multi-phase
      dissemination study with a cluster randomized trial component that will evaluate
      the dissemination of public health knowledge about evidence-based prevention of
      cancer and other chronic diseases. Phase one involves development of measures of
      practitioner views on and organizational supports for evidence-based public
      health and data collection using a national online survey involving state health
      department chronic disease practitioners. In phase two, a cluster randomized
      trial design will be conducted to test receptivity and usefulness of
      dissemination strategies directed toward state health department chronic disease
      practitioners to enhance capacity and organizational support for evidence-based
      chronic disease prevention. Twelve state health department chronic disease units
      will be randomly selected and assigned to intervention or control. State health
      department staff and the university-based study team will jointly identify,
      refine, and select dissemination strategies within intervention units.
      Intervention (dissemination) strategies may include multi-day in-person training
      workshops, electronic information exchange modalities, and remote technical
      assistance. Evaluation methods include pre-post surveys, structured qualitative
      phone interviews, and abstraction of state-level chronic disease prevention
      program plans and progress reports. TRIAL REGISTRATION: clinicaltrials.gov:
      NCT01978054.

PMID- 24330731
TI  - Metformin improves survival in intensive care unit patients, but why?

PMID- 24330728
TI  - Basic research and clinical applications of bisphosphonates in bone disease: what
      have we learned over the last 40 years?
AB  - It is now 40 years since bisphosphonates (BPs) were first used in the clinic. So,
      it is timely to provide a brief review of what we have learned about these agents
      in bone disease. BPs are bone-specific and have been classified into two major
      groups on the basis of their distinct molecular modes of action: amino-BPs and
      non-amino-BPs. The amino-BPs are more potent and they inhibit farnesyl
      pyrophosphate synthase (FPPS), a key enzyme of the mavalonate/cholesterol
      biosynthetic pathway, while the non-amino-BPs inhibit osteoclast activity, by
      incorporation into non-hydrolyzable analogs of ATP. Both amino-BPs and non-amino
      BPs can protect osteoblasts and osteocytes against apoptosis. The BPs are widely
      used in the clinic to treat various diseases characterized by excessive bone
      resorption, including osteoporosis, myeloma, bone metastasis, Legg-Perthes
      disease, malignant hyperparathyroidism, and other conditions featuring bone
      fragility. This review provides insights into some of the adverse effects of BPs,
      such as gastric irritation, osteonecrosis of the jaw, atypical femoral fractures,
      esophageal cancer, atrial fibrillation, and ocular inflammation. In conclusion,
      this review covers the biochemical and molecular mechanisms of action of BPs in
      bone, particularly the discovery that BPs have direct anti-apoptotic effects on
      osteoblasts and osteocytes, and the current situation of BP use in the clinic.

PMID- 24330732
TI  - Frequency of NFKBIA deletions is low in glioblastomas and skewed in glioblastoma
      neurospheres.
AB  - The NF-kB family of transcription factors is up-regulated in inflammation and
      different cancers. Recent data described heterozygous deletions of the NF-kB
      Inhibitor alpha gene (NFKBIA) in about 20% of glioblastomas (GBM): deletions were
      mutually exclusive with epidermal growth factor receptor (EGFR) amplification, a
      frequent event in GBM. We assessed the status of NFKBIA and EGFR in 69 primary
      GBMs and in corresponding neurospheres (NS). NFKBIA deletion was investigated by
      the copy number variation assay (CNV); EGFR amplification by CNV ratio with HGF;
      expression of EGFR and EGFRvIII by quantitative PCR or ReverseTranscriptase PCR.
      Heterozygous deletions of NFKBIA were present in 3 of 69 primary GBMs and,
      surprisingly, in 30 of 69 NS. EGFR amplification was detected in 36 GBMs: in
      corresponding NS, amplification was lost in 13 cases and reduced in 23 (10 vs 47
      folds in NS vs primary tumors; p < 0.001). The CNV assay was validated
      investigating HPRT1 on chromosome X in females and males. Results of array-CGH
      performed on 3 primary GBMs and 1 NS line were compatible with the CNV assay. NS
      cells with NFKBIA deletion had increased nuclear activity of p65 (RelA) and
      increased expression of the NF-kB target IL-6. In absence of EGF in the medium,
      EGFR amplification was more conserved and NFKBIA deletion less frequent point to
      a low frequency of NFKBIA deletions in GBM and suggest that EGF in the culture
      medium of NS may affect frequency not only of EGFR amplifications but also of
      NFKBIA deletions. 

PMID- 24330733
TI  - Comparisons of normal saline and lactated Ringer's resuscitation on hemodynamics,
      metabolic responses, and coagulation in pigs after severe hemorrhagic shock.
AB  - BACKGROUND: Ongoing improvements in trauma care now recommend earlier use of
      blood products as part of damage control resuscitation, but generally these
      products are not available at far forward battlefield locations. For the
      military, questions continue to arise regarding efficacy of normal saline (NS)
      vs. lactated Ringer's (LR). Thus, this study compared the effects of LR and NS
      after severe hemorrhage in pigs. METHODS: 20 anesthetized pigs were randomized
      into control (n = 6), LR (n = 7), and NS (n = 7) groups. Hemorrhage of 60%
      estimated total blood volume was induced in LR and NS groups by removing blood
      from the left femoral artery using a computer-controlled pump. Afterwards, the
      pigs were resuscitated with either LR at 3 times the bled volume or the volume of
      NS to reach the same mean arterial pressure (MAP) as in LR group. Hemodynamics
      were measured hourly and blood samples were taken at baseline (BL), 15 min, 3 h
      and 6 h after resuscitation to measure changes in coagulation using
      thrombelastograph(r). RESULTS: MAP was decreased by hemorrhage but returned to BL
      within 1 h after resuscitation with LR (119 +/- 7 ml/kg) or NS (183 +/- 9 ml/kg,
      p < 0.05). Base excess (BE) was decreased by hemorrhage; resuscitation with LR
      recovered BE but not with NS. Total peripheral resistance was decreased with NS
      and LR, with a larger drop shown in NS. Serum potassium was increased with NS,
      but not affected with LR. Coagulation changes were similar between LR and NS.
      CONCLUSIONS: NS may be inferior to LR in resuscitation due to its vasodilator
      effects and the risks of metabolic acidosis and hyperkalemia.

PMID- 24330734
TI  - Impact of land-use on malaria transmission in the Plateau region, southeastern
      Benin.
AB  - BACKGROUND: The goal of the study is to investigate if local agricultural
      practices have an impact on malaria transmission in four villages located in the
      same geographical area within a radius of 15 kilometers. Among the villages, one
      (Itassoumba) is characterized by the presence of a large market garden and
      fishpond basins, the three others (Itakpako, Djohounkolle and Ko-koumolou) are
      characterized by traditional food-producing agriculture. METHODS: Malaria
      transmission was evaluated using human-landing catches, both indoors and
      outdoors, two nights per month for 12 months. Field collected females An. gambiae
      s.l. were exposed for 1 hour to 0.75% permethrin and 0.05% deltamethrin using WHO
      insecticide susceptibility test kits and procedures. The presence of the kdr
      mutation was analyzed by PCR. RESULTS: Anopheles gambiae s.s form M (93.65%), was
      identified as the main malaria vector. Its susceptibility level to pyrethroids
      was the same (p > 0.05) in all villages. kdr mutation frequencies are 81.08 in
      Itakpako, 85 in Itassoumba, 79.73 in Djohounkolle and 86.84 in Ko-Koumolou (p =
      0.63). The entomological inoculation rate ranged from 9.62 to 21.65 infected
      bites of An. gambiae per human per year in Djohounkolle, Itakpako and Ko-Koumolou
      against 1159.62 in Itassoumba (p < 0.0001). CONCLUSION: The level of resistance
      of An. gambiae to pyrethroids was the same in the four villages. The
      heterogeneous character of malaria epidemiology was confirmed. The creation of
      fishponds basins and the development of market-gardening activities increased
      drastically the malaria transmission in Itassoumba.

PMID- 24330735
TI  - Analysis of cell hyperplasia and parietal cell dysfunction induced by Ostertagia
      ostertagi infection.
AB  - Infections in cattle with the gastric nematode Ostertagia ostertagi are
      associated with decreased acid secretion and profound physio-morphological
      changes of the gastric mucosa. The purpose of the current study was to
      investigate the mechanisms triggering these pathophysiological changes. O.
      ostertagi infection resulted in a marked cellular hyperplasia, which can be
      explained by increased transcriptional levels of signaling molecules related to
      the homeostasis of gastric epithelial cells such as HES1, WNT5A, FGF10, HB-EGF,
      AREG, ADAM10 and ADAM17. Intriguingly, histological analysis indicated that the
      rapid rise in the gastric pH, observed following the emergence of adult worms,
      cannot be explained by a loss of parietal cells, as a decrease in the number of
      parietal cells was only observed following a long term infection of several
      weeks, but is likely to be caused by an inhibition of parietal cell activity. To
      investigate whether this inhibition is caused by a direct effect of the
      parasites, parietal cells were co-cultured with parasite Excretory/Secretory
      products (ESP) and subsequently analyzed for acid production. The results
      indicate that adult ESP inhibited acid secretion, whereas ESP from the L4 larval
      stages did not alter parietal cell function. In addition, our data show that the
      inhibition of parietal cell activity could be mediated by a marked upregulation
      of inflammatory factors, which are partly induced by adult ESP in abomasal
      epithelial cells. In conclusion, this study shows that the emergence of adult O.
      ostertagi worms is associated with marked cellular changes that can be partly
      triggered by the worm's Excretory/secretory antigens. 

PMID- 24330737
TI  - Aripirazole augmentation in clozapine-associated obsessive-compulsive symptoms in
      schizophrenia.
AB  - OBJECTIVE: Patients with schizophrenia often experience comorbid obsessive
      compulsive symptoms. Within these patients, a significant subgroup developed
      secondary obsessive-compulsive symptoms during treatment with clozapine. METHOD:
      In this paper, we report on four cases in which adjunctive therapy with
      aripiprazole was tested to alleviate obsessive-compulsive symptoms in
      schizophrenia. RESULTS: All four patients had a significant improvement in
      obsessive-compulsive symptoms. The combination of clozapine and aripiprazole was
      well tolerated. CONCLUSION: This case series demonstrates the clinical efficacy
      of aripiprazole adjunctive therapy with clozapine in schizophrenic patients with
      comorbid obsessive-compulsive symptoms. Larger-sampled and controlled studies are
      required in order to test and confirm these observations.

PMID- 24330736
TI  - Porcine adipose-derived stem cells from buccal fat pad and subcutaneous adipose
      tissue for future preclinical studies in oral surgery.
AB  - INTRODUCTION: Adipose-derived stem cells (ASCs) are progenitor cells used in bone
      tissue engineering and regenerative medicine. Despite subcutaneous adipose tissue
      being more abundant, the buccal fat pad (BFP) is easily accessible for dentists
      and maxillofacial surgeons. For this reason, considering the need for preclinical
      study and the swine as an optimal animal model in tissue engineering
      applications, we compared the features of porcine ASCs (pASCs) from both tissue
      harvesting sites. METHODS: ASCs were isolated from interscapular subcutaneous
      adipose tissue (ScI) and buccal fat pads of six swine. Cells were characterized
      for their stemness and multipotent features. Moreover, their osteogenic ability
      when cultured on titanium disks and silicon carbide-plasma-enhanced chemical
      vapor-deposition fragments, and their growth in the presence of autologous and
      heterologous serum were also assessed. RESULTS: Independent of the harvesting
      site, no differences in proliferation, viability, and clonogenicity were observed
      among all the pASC populations. Furthermore, when induced toward osteogenic
      differentiation, both ScI- and BFP-pASCs showed an increase of collagen and
      calcified extracellular matrix (ECM) production, alkaline phosphatase activity,
      and osteonectin expression, indicating their ability to differentiate toward
      osteoblast-like cells. In addition, they differentiated toward adipocyte-like
      cells, and chondrogenic induced pASCs were able to increase glycosaminoglycans
      (GAGs) production over time. When cells were osteoinduced on synthetic
      biomaterials, they significantly increased the amount of calcified ECM compared
      with control cells; moreover, titanium showed the osteoinductive effect on pASCs,
      also without chemical stimuli. Finally, these cells grew nicely in 10% FBS, and
      no benefits were produced by substitution with swine serum. CONCLUSIONS: Swine
      buccal fat pad contains progenitor cells with mesenchymal features, and they also
      osteo-differentiate nicely in association with synthetic supports. We suggest
      that porcine BFP-ASCs may be applied in preclinical studies of periodontal and
      bone-defect regeneration.

PMID- 24330738
TI  - Antioxidant and cytoprotective activities of Piper betle, Areca catechu, Uncaria
      gambir and betel quid with and without calcium hydroxide.
AB  - BACKGROUND: Betel quid chewing is a popular habit in Southeast Asia. It is
      believed that chewing betel quid could reduce stress, strengthen teeth and
      maintain oral hygiene. The aim of this study was to investigate the antioxidant
      and cytoprotective activities of each of the ingredients of betel quid and
      compared with betel quid itself (with and without calcium hydroxide). The
      correlation of their cytoprotective and antioxidant activities with phenolic
      content was also determined. METHODS: Five samples (betel leaf, areca nut,
      gambir, betel quid and betel quid containing calcium hydroxide) were extracted in
      deionized distilled water for 12 hours at 37 degrees C. Antioxidant activities
      were evaluated for radical scavenging activity using DPPH assay, ferric reducing
      activity using FRAP assay and lipid peroxidation inhibition activity using FTC
      assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu
      procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective
      activity towards human gingival fibroblast cells was examined using MTT assay.
      RESULTS: Among the ingredients of betel quid, gambir demonstrated the highest
      antioxidant (DPPH - IC50 = 6.4 +/- 0.8 MUg/mL, FRAP - 5717.8 +/- 537.6 MUmol
      Fe(II)/mg), total phenolic content (TPC - 1142.5 +/- 106.8 MUg TAE/mg) and
      cytoprotective (100.1 +/- 4.6%) activities. Betel quid when compared with betel
      quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 +/-
      4.4 MUg/mL, FRAP - 1022.2 +/- 235.7 MUmol Fe(II)/mg), total phenolic content (TPC
      - 140.0 +/- 22.3 MUg TAE/mg), and cytoprotective (113.5 +/- 15.9%) activities.
      However, all of the five samples showed good lipid peroxidation inhibition
      compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as
      the major compound of gambir and betel quid. A positive correlation was observed
      between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and
      cytoprotective activity (r = 0.682). CONCLUSIONS: The betel quid has higher TPC,
      and antioxidant and cytoprotective activities than betel quid with calcium
      hydroxide. The quinic acid in betel quid may play an important role in the oral
      health protection.

PMID- 24330739
TI  - PROSPERO's progress and activities 2012/13.
AB  - PROSPERO is an international database of prospectively registered systematic
      reviews in health and social care. Between July 2012 and June 2013, 1,106
      registrations were added, bringing the total since launch in February 2011 to
      1,704. The value of the growing number of records is reflected in a 117% increase
      in page views in the first half of 2013 compared with the first half of 2012.
      Developments over the year included expansion of scope, improvement of the
      registration form and easier access to information on how to register. 

PMID- 24330741
TI  - Satellite clinics in academic ophthalmology programs: an exploratory study of
      successes and challenges.
AB  - BACKGROUND: Major academic ophthalmology departments have been expanding by
      opening multi-office locations ("satellites"). This paper offers a first glimpse
      into satellites of academic ophthalmology departments. METHODS: Leaders of seven
      medium to large, geographically diverse departments agreed to participate. One-
      to two-hour phone interviews were conducted to assess the features of their
      satellite practices. RESULTS: Success as clinical entities, profitability, and
      access to patients were stated goals for most satellites. In approximate
      descending order, refractive surgery, retina, oculoplastics, and pediatric
      ophthalmology were the most common subspecialties offered. Faculty staffing
      ranged from recruitment specifically for satellites to rotation of existing
      faculty. Except for a department with only one academic track, satellite doctors
      were a mix of tenure and mostly non-tenure track faculty. According to these
      department leaders, scholarly productivity of satellite faculty was similar to
      that of colleagues at the main campus, though research was more community-based
      and clinical in nature. Fellowship but little resident education occurred at
      satellites. Though it was agreed that satellite practices were integral to
      department finances, they accounted for a smaller percentage of revenues than of
      total departmental visits. CONCLUSIONS: Satellite offices have offered access to
      a better payor mix and have boosted the finances of academic ophthalmology
      departments. Challenges include maintaining collegiality with referring community
      physicians, integrating faculty despite geographic distance, preserving the
      department's academic "brand name," and ensuring consistent standards and
      operating procedures. Satellite clinics will likely help departments meet some of
      the challenges of health care reform.

PMID- 24330740
TI  - Characterization of phosphorus-regulated miR399 and miR827 and their isomirs in
      barley under phosphorus-sufficient and phosphorus-deficient conditions.
AB  - BACKGROUND: miR399 and miR827 are both involved in conserved phosphorus (P)
      deficiency signalling pathways. miR399 targets the PHO2 gene encoding E2 enzyme
      that negatively regulates phosphate uptake and root-to-shoot allocation, while
      miR827 targets SPX-domain-containing genes that negatively regulate other P
      responsive genes. However, the response of miR399 and miR827 to P conditions in
      barley has not been investigated. RESULTS: In this study, we investigated the
      expression profiles of miR399 and miR827 in barley (Hordeum vulagre L.) under P
      deficient and P-sufficient conditions. We identified 10 members of the miR399
      family and one miR827 gene in barley, all of which were significantly up
      regulated under deficient P. In addition, we found many isomirs of the miR399
      family and miR827, most of which were also significantly up-regulated under
      deficient P. Several isomirs of miR399 members were found to be able to cleave
      their predicted targets in vivo. Surprisingly, a few small RNAs (sRNAs) derived
      from the single-stranded loops of the hairpin structures of MIR399b and MIR399e-1
      were also found to be able to cleave their predicted targets in vivo. Many
      antisense sRNAs of miR399 and a few for miR827 were also detected, but they did
      not seem to be regulated by P. Intriguingly, the lowest expressed member, hvu
      miR399k, had four-fold more antisense sRNAs than sense sRNAs, and furthermore
      under P sufficiency, the antisense sRNAs are more frequent than the sense sRNAs.
      We identified a potential regulatory network among miR399, its target HvPHO2 and
      target mimics HvIPS1 and HvIPS2 in barley under P-deficient and P-sufficient
      conditions. CONCLUSIONS: Our data provide an important insight into the
      mechanistic regulation and function of miR399, miR827 and their isomirs in barley
      under different P conditions.

PMID- 24330742
TI  - Analysis of organ-enriched microRNAs in plasma as an approach to development of
      Universal Screening Test: feasibility study.
AB  - BACKGROUND: Early disease detection with a minimally invasive screening test will
      significantly increase effectiveness and decrease the cost of treatment. Here we
      propose a framework of a novel approach - Universal Screening Test (UST) for the
      detection of pathological processes in a particular organ system, organ, or
      tissue by RT-qPCR analysis of circulating cell-free miRNAs in plasma. As the
      first step towards assessing the feasibility of this concept, the present study
      was designed to analyze whether the same microRNAs (miRNAs) can detect various
      diseases of a particular organ system. METHODS: RNA was extracted from plasma
      using Trizol treatment and silica binding. Levels of miRNAs were measured by
      single target RT-qPCR. The following innovations have been tested and proven
      effective: (i) the use of organ system/organ/tissue-enriched miRNAs; (ii) the use
      of miRNAs associated with broad disease categories, such as cancer and
      inflammation, in combination with the organ-enriched miRNAs; and (iii) the use of
      "miRNA pairs" for selecting miRNA combinations with the highest sensitivity and
      specificity. RESULTS: Here we report biomarker miRNA pairs effectively
      differentiating (i) patients with pulmonary system diseases (asthma, pneumonia
      and non-small cell lung cancer) and gastrointestinal (GI) system diseases
      (Crohn's disease, stages I/II esophageal, gastric and colon cancers) from
      controls, each with 95% accuracy; (ii) patients with a pathology of the pulmonary
      system from patients with a pathology of the GI system with 94% accuracy; and
      (iii) cancer patients (stages I/II esophageal, gastric, colon cancers, or non
      small cell lung cancer) from patients with inflammatory diseases (asthma,
      pneumonia, or Crohn's disease) with 93%-95% accuracy. CONCLUSIONS: The results
      obtained in the present study, along with the data reported by us and others
      previously, are encouraging and lay the ground for further investigation of the
      described approach for UST development.

PMID- 24330743
TI  - Intestinal obstruction due to a left paraduodenal hernia: a case report.
AB  - INTRODUCTION: A left paraduodenal hernia is a rare congenital malrotational
      anomaly of the midgut that occurs in the paraduodenal fossa of Landzert to the
      left of the fourth duodenum. It is responsible for approximately 1% of small
      bowel obstructions. CASE PRESENTATION: We report a case of left paraduodenal
      hernia combined with small bowel obstruction in a 47-year-old Mediterranean woman
      who had a history of recurrent abdominal pain. An abdominal computed tomography
      scan showed a saclike mass clustered in the left upper quadrant but failed to
      yield a clear diagnosis. We describe the surgical anatomy of this disease and the
      emergency surgical management together with a short review of the literature.
      CONCLUSIONS: Even though a left paraduodenal hernia is rare, it must be suspected
      in any upper intestinal occlusion. The high morbidity and mortality rate of
      complicated cases should motivate preventive treatment in case of incidental
      operative discovery.

PMID- 24330744
TI  - Procalcitonin-guided therapy in intensive care unit patients with severe sepsis
      and septic shock--a systematic review and meta-analysis.
AB  - INTRODUCTION: Procalcitonin (PCT) algorithms for antibiotic treatment decisions
      have been studied in adult patients from primary care, emergency department, and
      intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy
      may reduce antibiotic exposure without increasing the mortality rate. However,
      information on the efficacy and safety of this approach in the most vulnerable
      population of critically ill patients with severe sepsis and septic shock is
      missing. METHOD: Two reviewers independently performed a systematic search in
      PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane
      Central Register of Controlled Trials, http://www.ClinicalTrials.gov and
      http://www.ISRCTN.org. Eligible studies had to be randomized controlled clinical
      trials or cohort studies which compare procalcitonin-guided therapy with standard
      care in severe sepsis patients and report at least one of the following outcomes:
      hospital mortality, 28-day mortality, duration of antimicrobial therapy, length
      of stay in the intensive care unit or length of hospital stay. Disagreements
      about inclusion of studies and judgment of bias were solved by consensus.
      RESULTS: Finally seven studies comprising a total of 1,075 patients with severe
      sepsis or septic shock were included in the meta-analysis. Both hospital
      mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and
      28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between
      procalcitonin-guided therapy and standard treatment groups. Duration of
      antimicrobial therapy was significantly reduced in favor of procalcitonin-guided
      therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the
      length of stay in the ICU and in hospital did not differ between groups.
      CONCLUSION: Procalcitonin-guided therapy is a helpful approach to guide
      antibiotic therapy and surgical interventions without a beneficial effect on
      mortality. The major benefit of PCT-guided therapy consists of a shorter duration
      of antibiotic treatment compared to standard care. Trials are needed to
      investigate the effect of PCT-guided therapy on mortality, length of ICU and in
      hospital stay in severe sepsis patients.

PMID- 24330745
TI  - Depression and decision-making capacity for treatment or research: a systematic
      review.
AB  - BACKGROUND: Psychiatric disorders can pose problems in the assessment of decision
      making capacity (DMC). This is so particularly where psychopathology is seen as
      the extreme end of a dimension that includes normality. Depression is an example
      of such a psychiatric disorder. Four abilities (understanding, appreciating,
      reasoning and ability to express a choice) are commonly assessed when determining
      DMC in psychiatry and uncertainty exists about the extent to which depression
      impacts capacity to make treatment or research participation decisions. METHODS:
      A systematic review of the medical ethical and empirical literature concerning
      depression and DMC was conducted. Medline, EMBASE and PsycInfo databases were
      searched for studies of depression and consent and DMC. Empirical studies and
      papers containing ethical analysis were extracted and analysed. RESULTS: 17
      publications were identified. The clinical ethics studies highlighted
      appreciation of information as the ability that can be impaired in depression,
      indicating that emotional factors can impact on DMC. The empirical studies
      reporting decision-making ability scores also highlighted impairment of
      appreciation but without evidence of strong impact. Measurement problems,
      however, looked likely. The frequency of clinical judgements of lack of DMC in
      people with depression varied greatly according to acuity of illness and whether
      judgements are structured or unstructured. CONCLUSIONS: Depression can impair DMC
      especially if severe. Most evidence indicates appreciation as the ability
      primarily impaired by depressive illness. Understanding and measuring the
      appreciation ability in depression remains a problem in need of further research.

PMID- 24330746
TI  - Analysis of equivalent uniform dose (EUD) and conventional radiation treatment
      parameters after primary and re-irradiation of malignant glioma.
AB  - BACKGROUND: Re-irradiation is a reasonable second treatment option for patients
      with recurrent malignant glioma (MG) after previous radio(chemo)therapy. However,
      only limited data is available allowing for a precise selection of patients
      suitable for re-treatment in regard to safety and efficacy. METHODS: Using the
      department database, 58 patients with two courses of percutaneous radiation were
      identified. Besides classical dose-volume histogram (DVH) parameters equivalent
      uniform dose (EUD) values were calculated for the tumor and organs at risk
      (OARs), retrospectively analyzed and correlated to survival outcome parameters.
      Cumulative EUD values were also calculated in all cases where previous OAR DVHs
      were available. RESULTS: Median follow-up was 265 days and no relevant toxicity
      was observed after re-irradiation in our patient cohort during follow-up. Time
      interval between first and second irradiation was regularly above 6 months. As a
      conservative estimation of the cumulative EUD to the OARs, the EUDs of first and
      second irradiation were added. Median cumulative EUD to the optic chiasm was 48.8
      Gy (range, 2.5-76.5 Gy), 57.4 Gy (range, 2.7-75.3 Gy) to the brainstem, 20.9/22.1
      Gy (range, 0.0-68.3 Gy) to the right/left optic nerve and 73.8 Gy (range, 64.9
      77.3 Gy) to the brain. No correlation between treated volume and survival was
      seen. CONCLUSIONS: This study provides retrospective estimates on cumulative
      doses at the OARs. EUD values are derived and may serve as reference for further
      studies, including planning studies where specific constraints are needed.

PMID- 24330747
TI  - Evaluating larval mosquito resource partitioning in western Kenya using stable
      isotopes of carbon and nitrogen.
AB  - BACKGROUND: In sub-Saharan Africa, malaria, transmitted by the Anopheles
      mosquito, remains one of the foremost public health concerns. Anopheles gambiae,
      the primary malaria vector in sub-Saharan Africa, is typically associated with
      ephemeral, sunlit habitats; however, An. gambiae larvae often share these
      habitats with other anophelines along with other disease-transmitting and benign
      mosquito species. Resource limitations within habitats can constrain larval
      density and development, and this drives competitive interactions among and
      between species. METHODS: We used naturally occurring stable isotope ratios of
      carbon and nitrogen to identify resource partitioning among co-occurring larval
      species in microcosms and natural habitats in western Kenya. We used two and
      three source mixing models to estimate resource utilization (i.e. bacteria,
      algae, organic matter) by larvae. RESULTS: Laboratory experiments revealed larval
      delta13C and delta15N composition to reflect the food sources they were reared
      on. Resource partitioning was demonstrated between An. gambiae and Culex
      quinquefasciatus larvae sharing the same microcosms. Differences in larval
      delta13C and delta15N content was also evident in natural habitats, and Anopheles
      species were consistently more enriched in delta13C when compared to culicine
      larvae. CONCLUSIONS: These observations demonstrate inter-specific resource
      partitioning between Cx. quinquefasciatus and An. gambiae larvae in natural
      habitats in western Kenya. This information may be translated into opportunities
      for targeted larval control efforts by limiting specific larval food resources,
      or through bio-control utilizing competitors at the same trophic level.

PMID- 24330748
TI  - Id4 dependent acetylation restores mutant-p53 transcriptional activity.
AB  - BACKGROUND: The mechanisms that can restore biological activity of mutant p53 are
      an area of high interest given that mutant p53 expression is observed in one
      third of prostate cancer. Here we demonstrate that Id4, an HLH transcriptional
      regulator and a tumor suppressor, can restore the mutant p53 transcriptional
      activity in prostate cancer cells. METHODS: Id4 was over-expressed in prostate
      cancer cell line DU145 harboring mutant p53 (P223L and V274F) and silenced in
      LNCaP cells with wild type p53. The cells were used to quantitate apoptosis, p53
      localization, p53 DNA binding and transcriptional activity. Immuno-precipitation/
      blot studies were performed to demonstrate interactions between Id4, p53 and
      CBP/p300 and acetylation of specific lysine residues within p53. RESULTS: Ectopic
      expression of Id4 in DU145 cells resulted in increased apoptosis and expression
      of BAX, PUMA and p21, the transcriptional targets of p53. Mutant p53 gained DNA
      binding and transcriptional activity in the presence of Id4 in DU145 cells.
      Conversely, loss of Id4 in LNCaP cells abrogated wild type p53 DNA binding and
      transactivation potential. Gain of Id4 resulted in increased acetylation of
      mutant p53 whereas loss of Id4 lead to decreased acetylation in DU145 and LNCaP
      cells respectively. Id4 dependent acetylation of p53 was in part due to a
      physical interaction between Id4, p53 and acetyl-transferase CBP/p300.
      CONCLUSIONS: Taken together, our results suggest that Id4 regulates the activity
      of wild type and mutant p53. Id4 promoted the assembly of a macromolecular
      complex involving CBP/P300 that resulted in acetylation of p53 at K373, a
      critical post-translational modification required for its biological activity.

PMID- 24330749
TI  - Predictive risk stratification model: a progressive cluster-randomised trial in
      chronic conditions management (PRISMATIC) research protocol.
AB  - BACKGROUND: An ageing population increases demand on health and social care. New
      approaches are needed to shift care from hospital to community and general
      practice. A predictive risk stratification tool (Prism) has been developed for
      general practice that estimates risk of an emergency hospital admission in the
      following year. We present a protocol for the evaluation of Prism.
      METHODS/DESIGN: We will undertake a mixed methods progressive cluster-randomised
      trial. Practices begin as controls, delivering usual care without Prism.
      Practices will receive Prism and training randomly, and thereafter be able to use
      Prism with clinical and technical support. We will compare costs, processes of
      care, satisfaction and patient outcomes at baseline, 6 and 18 months, using
      routine data and postal questionnaires. We will assess technical performance by
      comparing predicted against actual emergency admissions. Focus groups and
      interviews will be undertaken to understand how Prism is perceived and adopted by
      practitioners and policy makers. We will model data using generalised linear
      models and survival analysis techniques to determine whether any differences
      exist between intervention and control groups. We will take account of covariates
      and explanatory factors. In the economic evaluation we will carry out a cost
      effectiveness analysis to examine incremental cost per emergency admission to
      hospital avoided and will examine costs versus changes in primary and secondary
      outcomes in a cost-consequence analysis. We will also examine changes in quality
      of life of patients across the risk spectrum. We will record and transcribe focus
      groups and interviews and analyse them thematically. We have received full
      ethical and R and D approvals for the study and Information Governance Review
      Panel (IGRP) permission for the use of routine data. We will comply with the
      CONSORT guidelines and will disseminate the findings at national and
      international conferences and in peer-reviewed journals. DISCUSSION: The proposed
      study will provide information on costs and effects of Prism; how it is used in
      practice, barriers and facilitators to its implementation; and its perceived
      value in supporting the management of patients with and at risk of developing
      chronic conditions. TRIAL REGISTRATION: Controlled Clinical Trials ISRCTN no.
      ISRCTN55538212.

PMID- 24330750
TI  - Can audiometric results predict qualitative hearing improvements in bone-anchored
      hearing aid recipients?
AB  - INTRODUCTION: Patients receiving a bone-anchored hearing aid have well-documented
      improvements in their quality of life and audiometric performance. However, the
      relationship between audiometric measurements and subjective improvement is not
      well understood. METHODS: Adult patients enrolled in the Nova Scotia bone
      anchored hearing aid programme were identified. The pure tone average for fitting
      the sound-field threshold, as well as the better and worse hearing ear bone
      conduction and air conduction levels, were collected pre-operatively. Recipients
      were asked to complete the Speech, Spatial and Qualities of Hearing
      questionnaire; their partners were asked to complete a pre- and post-bone
      anchored hearing aid fitting Hearing Handicap Inventory for Adults questionnaire.
      RESULTS: Forty-eight patients who completed and returned the Speech, Spatial and
      Qualities of Hearing questionnaire had partners who completed the Hearing
      Handicap Inventory for Adults questionnaire. The results from the Speech, Spatial
      and Qualities of Hearing questionnaire correlated with the sound-field hearing
      threshold post-bone-anchored hearing aid fitting and the pure tone average of the
      better hearing ear bone conduction (total Speech, Spatial and Qualities of
      Hearing Scale to the pre-operative better hearing ear air curve (r = 0.3); worse
      hearing ear air curve (r = 0.27); post-operative, bone-anchored hearing aid-aided
      sound-field thresholds (r = 0.35)). An improvement in sound-field threshold
      correlated only with spatial abilities. In the Hearing Handicap Inventory for
      Adults questionnaire, there was no correlation between the subjective evaluation
      of each patient and their partner. CONCLUSION: The subjective impressions of
      hearing aid recipients with regards to speech reception and the spatial qualities
      of hearing correlate well with pre-operative audiometric results. However, the
      overall magnitude of sound-field improvement predicts an improvement of spatial
      perception, but not other aspects of hearing, resulting in hearing aid recipients
      having strongly disparate subjective impressions when compared to those of their
      partners.

PMID- 24330751
TI  - Magnetic targeting enhances retrograde cell retention in a rat model of
      myocardial infarction.
AB  - INTRODUCTION: Retrograde coronary venous infusion is a promising delivery method
      for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the
      establishment of this method as the preferred route for cell delivery. Here, we
      explored whether magnetic targeting could enhance retrograde cell retention in a
      rat model of myocardial infarction. METHODS: Rat mesenchymal stem cells were
      labeled with superparamagnetic oxide nanoparticles. The magnetic responsiveness
      of MSCs was observed while cells flowed through a tube that served as a model of
      blood vessels in a 0.6-Tesla magnetic field. In a Sprague-Dawley rat model of
      acute myocardial infarction, 1 * 106 magnetic mesenchymal stem cells were
      transjugularly injected into the left cardiac vein while a 0.6-Tesla magnet was
      placed above the heart. The cardiac retention of transplanted cells was assessed
      by using quantitative Y chromosome-specific polymerase chain reaction, cardiac
      magnetic resonance imaging, and optical imaging. Cardiac function was measured by
      using echocardiography, and histologic analyses of infarct morphology and
      angiogenesis were obtained. RESULTS: The flowing iron oxide-labeled mesenchymal
      stem cells were effectively attracted to the area where the magnet was
      positioned. Twenty-four hours after cellular retrocoronary delivery, magnetic
      targeting significantly increased the cardiac retention of transplanted cells by
      2.73- to 2.87-fold. Histologic analyses showed that more transplanted cells were
      distributed in the anterior wall of the left ventricle. The enhanced cell
      engraftment persisted for at least 3 weeks, at which time, left ventricular
      remodeling was attenuated, and cardiac function benefit was improved.
      CONCLUSIONS: These results suggest that magnetic targeting offers new
      perspectives for retrograde coronary venous delivery to enhance cell retention
      and subsequent functional benefit in heart diseases

PMID- 24330752
TI  - Assessment of cardiac pathology by point-of-care ultrasonography performed by a
      novice examiner is comparable to the gold standard.
AB  - BACKGROUND: The aim of the study was to compare the diagnostic accuracy of point
      of-care cardiac ultrasonography performed by a novice examiner against results
      from a specialist in cardiology with expert skills in echocardiography, with
      regard to the assessment of six clinically relevant cardiac conditions in a
      population of ward patients from the Department of Cardiology or the Department
      of Cardiothoracic Surgery. METHODS: Cardiac ultrasonography was performed by a
      novice examiner at the bedside and images were interpreted in a point-of-care
      context with dichotomous outcomes (yes/no). Six outcome categories were defined:
      1) pericardial effusion (>=10 mm), 2) left ventricular dilatation (>=62 mm), 3)
      right ventricular dilatation (>=42 mm or >= left ventricular diameter), 4) left
      ventricular hypertrophy (>=13 mm), 5) left ventricular failure (EF <= 40%), 6)
      aortic stenosis (maximum flow velocity >=3 m/s). The examiner was blinded to the
      patients' medical history and results from previous echocardiographic
      examinations. Results from the interpreted point-of-care ultrasonography
      examination were compared with echocardiographic diagnosis made by a specialist
      in cardiology. RESULTS: A total of 102 medical and surgical patients were
      included. Assessments were made in six categories totalling 612 assessments.
      There was agreement between the novice examiner and the specialist in 95.6% of
      the cases; overall sensitivity was 0.91 and specificity was 0.97. Positive
      predictive value was 0.92 and negative predictive value was 0.97. Kappa
      statistics showed good agreement between observers (kappa=0.88). CONCLUSIONS:
      This study showed that a novice examiner was able to detect common and
      significant heart pathology in six different categories with good accuracy using
      POC ultrasonography.

PMID- 24330753
TI  - Is prehospital endotracheal intubation associated with improved outcomes in
      isolated severe head injury? A matched cohort analysis.
AB  - INTRODUCTION: Prehospital endotracheal intubation (ETI) following traumatic brain
      injury in urban settings is controversial. Studies investigating admission
      arterial blood gas (ABG) patterns in these instances are scant. HYPOTHESIS:
      Outcomes in patients subjected to divergent prehospital airway management options
      following severe head injury were studied. METHODS: This was a retrospective
      propensity-matched study in patients with isolated TBI (head Abbreviated Injury
      Scale (AIS) >= 3) and Glasgow Coma Scale (GCS) score of <= 8 admitted to a Level
      1 urban trauma center from January 1, 2003 through October 31, 2011. Cases that
      had prehospital ETI were compared to controls subjected to oxygen by mask in a
      one to three ratio for demographics, mechanism of injury,
      tachycardia/hypotension, Injury Severity Score, type of intracranial lesion, and
      all major surgical interventions. Primary outcome was mortality and secondary
      outcomes included admission gas profile, in-hospital morbidity, ICU length of
      stay (ICU LOS) and hospital length of stay (HLOS). RESULTS: Cases (n = 55) and
      controls (n = 165) had statistically similar prehospital and in-hospital
      variables after propensity matching. Mortality was significantly higher for the
      ETI group (69.1% vs 55.2% respectively, P = .011). There was no difference in pH,
      base deficit, and pCO2 on admission blood gases; however the ETI group had
      significantly lower pO2 (187 (SD = 14) vs 213 (SD = 13), P = .034). There was a
      significantly increased incidence of septic shock in the ETI group. Patients
      subjected to prehospital ETI had a longer HLOS and ICU LOS. CONCLUSION: In
      isolated severe traumatic brain injury, prehospital endotracheal intubation was
      associated with significantly higher adjusted mortality rate and worsened
      admission oxygenation. Further prospective validation of these findings is
      warranted.

PMID- 24330754
TI  - Challenges in cardiac device innovation: is neuroimaging an appropriate endpoint?
      Consensus from the 2013 Yale-UCL Cardiac Device Innovation Summit.
AB  - BACKGROUND: Neurological events associated with transcatheter aortic valve
      implantation are major contributors to morbidity and mortality. Choosing an
      appropriate endpoint to determine neuroprotection device efficacy is a key
      difficulty inhibiting the translation of the innovation from the laboratory to
      the bedside. Cost and sample size limitations inhibit the feasibility of using
      the rate of clinical (such as stroke or other cerebral) events as the primary
      efficacy endpoint. This paper focuses on consensus opinions from the 2013 Yale
      University College London (UCL) Device Innovation Summit. DISCUSSION:
      Neuroimaging, specifically diffusion-weighted magnetic resonance imaging (DW
      MRI), may serve as a surrogate endpoint for clinical studies detecting cerebral
      events in which cost and sample-size limitations prohibit the use of clinical
      outcomes. A major limitation of using imaging to prove efficacy in cardiac device
      studies is that no standardized endpoint exists. Ongoing trials investigating
      cerebral protection devices for transcatheter aortic valve implantation are
      utilizing and reporting various qualitative and quantitative DW MRI values;
      however, single lesion volume, number of new lesions, and total lesion volume
      have been found to be the most reproducible and prognostically important imaging
      measures. SUMMARY: DW MRI may be a useful surrogate endpoint for clinical studies
      detecting cerebral events to determine the device's success in neurological
      protection. Consensus from the 2013 Yale-UCL Device Innovation Summit
      specifically recommends the reporting of mean single lesion volume, number of new
      lesions, and total volume, and encourages European Union (EU)-US regulatory
      consensus in the guidance of implementing this endpoint.

PMID- 24330755
TI  - Burden of pneumocystis pneumonia in HIV-infected adults in sub-Saharan Africa:
      protocol for a systematic review.
AB  - BACKGROUND: Reports from Africa have suggested that pneumocystis pneumonia (PCP)
      is a less important cause of morbidity than in the developed world. However, more
      recent studies have shown high seroprevalence rates of P. jirovecii in healthy
      individuals with HIV as well as high rates of clinical disease in African
      children. This suggests that PCP may be more common in Africa than was previously
      recognised. Understanding the contribution of PCP to disease in HIV-infected
      individuals in sub-Saharan Africa (SSA) has important implications for diagnosis,
      management and resource allocation. We therefore propose to conduct a systematic
      review and meta-analysis in order to investigate the burden of PCP in this
      population. METHODS AND DESIGN: We plan to search electronic databases and
      reference lists of relevant articles published from 1995 to May 2013 using broad
      terms for pneumocystis, HIV/AIDS and sub-Saharan Africa. Studies will be included
      if they provide clear diagnostic criteria for PCP and well-defined study
      populations or mortality data (denominator). A novel quality score assessment
      tool has been developed to ensure fidelity to inclusion criteria, minimise risk
      of selection bias between reviewers and to assess quality of outcome
      ascertainment. This will be applied to eligible full-text articles. We will
      extract data using a standardised form and perform descriptive and quantitative
      analysis to assess PCP prevalence, mortality and case fatality, as well as the
      quality of included studies. This review protocol has been published in the
      PROSPERO International Prospective Register of systematic reviews, registration
      number CRD42013005530. DISCUSSION: Our planned review will contribute to the
      diagnosis and management of community-acquired pneumonia in HIV-infected
      individuals in SSA by systematically assessing the burden of PCP in this
      population. We also describe a novel quality assessment tool that may be applied
      to other prevalence reviews.

PMID- 24330756
TI  - A novel dominant glossy mutation causes suppression of wax biosynthesis pathway
      and deficiency of cuticular wax in Brassica napus.
AB  - BACKGROUND: The aerial parts of land plants are covered with cuticular waxes that
      limit non-stomatal water loss and gaseous exchange, and protect plants from
      ultraviolet radiation and pathogen attack. This is the first report on the
      characterization and genetic mapping of a novel dominant glossy mutant (BnaA.GL)
      in Brassica napus. RESULTS: Transmission electron microscopy revealed that the
      cuticle ultrastructure of GL mutant leaf and stem were altered dramatically
      compared with that of wide type (WT). Scanning electron microscopy corroborated
      the reduction of wax on the leaf and stem surface. A cuticular wax analysis of
      the GL mutant leaves further confirmed the drastic decrease in the total wax
      content, and a wax compositional analysis revealed an increase in aldehydes but a
      severe decrease in alkanes, ketones and secondary alcohols. These results
      suggested a likely blockage of the decarbonylation step in the wax biosynthesis
      pathway. Genetic mapping narrowed the location of the BnaA.GL gene to the end of
      A9 chromosome. A single-nucleotide polymorphism (SNP) chip assay in combination
      with bulk segregant analysis (BSA) also located SNPs in the same region. Two
      SNPs, two single sequence repeat (SSR) markers and one IP marker were located on
      the flanking region of the BnaA.GL gene at a distance of 0.6 cM. A gene
      homologous to ECERIFERUM1 (CER1) was located in the mapped region. A cDNA
      microarray chip assay revealed coordinated down regulation of genes encoding
      enzymes of the cuticular wax biosynthetic pathway in the glossy mutant, with
      BnCER1 being one of the most severely suppressed genes. CONCLUSIONS: Our results
      indicated that surface wax biosynthesis is broadly affected in the glossy mutant
      due to the suppression of the BnCER1 and other wax-related genes. These findings
      offer novel clues for elucidating the molecular basis of the glossy phenotype.

PMID- 24330757
TI  - Effects of dehydrated lucerne and soya bean meal on milk production and
      composition, nutrient digestion, and methane and nitrogen losses in dairy cows
      receiving two different forages.
AB  - Dehydrated lucerne is used as a protein source in dairy cow rations, but little
      is known about the effects of lucerne on greenhouse gas production by animals.
      Eight Holstein dairy cows (average weight: 582 kg) were used in a replicated 4 *
      4 Latin square design. They received diets based on either maize silage (M) or
      grass silage (G) (45% of diet on dry matter (DM) basis), with either soya bean
      meal (15% of diet DM) completed with beet pulp (15% of diet DM) (SP) or
      dehydrated lucerne (L) (30% of diet DM) as protein sources; MSP, ML, GSP and GL
      diets were calculated to meet energy requirements for milk production by dairy
      cows and degradable protein for rumen microbes. Dry matter intake (DMI) did not
      differ among diets (18.0 kg/day DMI); milk production was higher with SP diets
      than with L diets (26.0 v. 24.1 kg/day), but milk production did not vary with
      forage type. Milk fatty-acid (FA) composition was modified by both forage and
      protein sources: L and G diets resulted in less saturated FA, less linoleic acid,
      more trans-monounsaturated FA, and more linolenic acid than SP and M diets,
      respectively. Enteric methane (CH4) production, measured by the SF6 tracer
      method, was higher for G diets than for M diets, but did not differ with protein
      source. The same effects were observed when CH4 was expressed per kg milk. Minor
      effects of diets on rumen fermentation pattern were observed. Manure CH4
      emissions estimated from faecal organic matter were negatively related to diet
      digestibility and were thus higher for L than SP diets, and higher for M than G
      diets; the resulting difference in total CH4 production was small. Owing to diet
      formulation constraints, N intake was higher for SP than for L diets; interaction
      between forage type and protein source was significant for N intake. The same
      statistical effects were found for N in milk. Faecal and urinary N losses were
      determined from total faeces and urine collection. Faecal N output was lower for
      M than for G diets but did not differ between protein sources. Urinary N output
      did not differ between forage types, but was lower for cows fed L diets than for
      cows fed SP diets, potentially resulting in lower ammonia emissions with L diets.
      Replacing soya bean meal plus beet pulp with dehydrated lucerne did not change
      CH4 production, but resulted in more N in faeces and less N in urine.

PMID- 24330758
TI  - Who uses emergency departments inappropriately and when - a national cross
      sectional study using a monitoring data system.
AB  - BACKGROUND: Increasing pressures on emergency departments (ED) are straining
      services and creating inefficiencies in service delivery worldwide. A potentially
      avoidable pressure is inappropriate attendances (IA); typically low urgency, self
      referred patients better managed by other services. This study examines
      demographics and temporal trends associated with IA to help inform measures to
      address them. METHODS: Using a national ED dataset, a cross-sectional examination
      of ED attendances in England from April 2011 to March 2012 (n = 15,056,095) was
      conducted. IA were defined as patients who were self-referred; were not attending
      a follow-up; received no investigation and either no treatment or
      'guidance/advice only'; and were discharged with either no follow-up or follow-up
      with primary care. Small, nationally representative areas were used to assign
      each attendance to a residential measure of deprivation. Multivariate analysis
      was used to predict relationships between IA, demographics (age, gender,
      deprivation) and temporal factors (day, month, hour, bank holiday, Christmas
      period). RESULTS: Overall, 11.7% of attendances were categorized as
      inappropriate. IA peaked in early childhood (adjusted odds ratio (AOR) = 1.53 for
      both one and two year olds), and was elevated throughout late-teens and young
      adulthood, with odds reducing steadily from age 27 (reference category, age 40).
      Both IA and appropriate attendances (AA) were most frequent in the most deprived
      populations. However, relative to AA, those living in the least deprived areas
      had the highest odds of IA (AOR = 0.89 in most deprived quintile). Odds of IA
      were also higher for males (AOR = 0.95 in females). Both AA and IA were highest
      on Mondays, whilst weekends, bank holidays and the period between 8 am and 4 pm
      saw more IA relative to AA. CONCLUSIONS: Prevention of IA would be best targeted
      at parents of young children and at older youths/young adults, and during
      weekends and bank holidays. Service provision focusing on access to primary care
      and EDs serving the most deprived communities would have the most benefit.
      Improvements in coverage and data quality of the national ED dataset, and the
      addition of an appropriateness field, would make this dataset an effective
      monitoring tool to evaluate interventions addressing this issue.

PMID- 24330759
TI  - Urinary amylase/urinary creatinine ratio (uAm/uCr)--a less-invasive parameter for
      management of hyperamylasemia.
AB  - BACKGROUND: The serum level of amylase (sAm) is commonly used as a biochemical
      marker for diagnosis and management of pancreatic disorders. However, the use of
      the urine level of amylase (uAm) is limited in practice, because the diagnostic
      ability of uAm is inferior to that of sAm. In the present study, the possible
      concordance of uAm-rerated parameters with sAm was investigated, and evaluate the
      usefulness of uAm for management of hyperamylasemia. METHODS: From June 1995 to
      October 2009, 804 samples of both urine and blood were collected from 128
      patients in order to measure the serum level of amylase (sAm) and the urine level
      of amylase (uAm) and creatinine (uCr). Concordance of parameters using uAm
      compared to sAm was assessed. Parameters used were uAm, amylase creatinine
      clearance ratio (ACCR), and the ratio of uAm to uCr (uAm/uCr). RESULTS: uAm/uCr
      had the best correlation with sAm (r = 0.779, p < 0.001) compared to uAm (r =
      0.620, p < 0.001) and to ACCR (r = 0.374, p < 0.001), when sAm was over the
      standard level. The area under the receiver operating characteristic curve of
      uAm/uCr (0.884) was significantly higher than that of uAm (0.766) and of ACCR
      (0.666) (p < 0.001 for each). The cutoff value of uAm/uCr was 569.8, with a
      sensitivity of 81.0% and a specificity of 83.1%. CONCLUSIONS: The uAm/uCr ratio
      correlated with sAm, and may be an alternative to sAm for prediction of
      hyperamylasemia. Use of urine samples results in a decreased need for blood
      sampling, which is especially beneficial in pediatric patients.

PMID- 24330760
TI  - Field evaluation of alphacypermethrin in indoor residual spraying for
      leishmaniasis control in an endemic area, northern Morocco.
AB  - BACKGROUND: In Morocco, the main strategies of leishmaniasis vector control are
      based on environmental modifications. Use of local residual indoor spraying with
      synthetic pyrethroids is often envisaged. The need to evaluate this control
      method is essential. The current study was conducted to determine the efficacy of
      an alphacypermethrin IRS program against leishmaniasis vectors in an endemic area
      in the north of Morocco. METHODS: The survey was conducted in four neighbouring
      localities in three different districts in northern Morocco: Ait Chaib and
      Aichoun in Sefrou district, Bouassem (Boulmane) and Lmrouj (Taounate). Indoor
      residual spraying with alphacypermethrin at a dose of 30 mg/m2 was used in Ait
      Chaib and Lmrouj localities during 2010, 2011 and 2012, while localities of
      Aichoun and Bouassem were taken as control. In the four studied areas, sand flies
      were collected bimonthly from April to November in 2011 and 2012, using sticky
      traps, to determine their abundance and feeding pattern. Alphacypermethrin IRS
      were evaluated for their residual effect using the WHO cone bioassay test.
      Leishmaniasis incidence was estimated by passive and active case detection in
      each study area. RESULTS: Significant reductions in leishmaniasis incidence and
      in gravidity rate were observed when comparing sprayed and unsprayed localities.
      The residual activity of alphacypermethrin at the concentration used lasted 10
      weeks after spraying. However, the abundance of sand flies was not significantly
      affected by alphacypermethrin IRS. CONCLUSION: This study indicated that IRS has
      a significant impact on leishmaniasis transmission; therefore it could be
      recommended as an effective tool for leishmaniasis control in areas with high
      leishmaniasis transmission.

PMID- 24330761
TI  - The use of Cincinnati Prehospital Stroke Scale during telephone dispatch
      interview increases the accuracy in identifying stroke and transient ischemic
      attack symptoms.
AB  - BACKGROUND: Timely and appropriate hospital treatment of acute cerebrovascular
      diseases (stroke and Transient Ischemic Attacks - TIA) improves patient outcomes.
      Emergency Medical Service (EMS) dispatchers who can identify cerebrovascular
      disease symptoms during telephone requests for emergency service also contribute
      to these improved outcomes. The Italian Ministry of Health issued guidelines on
      the management of AC patients in pre-hospital emergency service, including
      Cincinnati Prehospital Stroke Scale (CPSS) use.We measured the sensitivity and
      Positive Predictive Value (PPV) of EMS dispatchers' ability to recognize
      stroke/TIA symptoms and evaluated whether the CPSS improves accuracy. METHODS: A
      cross-sectional multicentre study was conducted to collect data from 38 Italian
      emergency operative centres on all cases identified with stroke/TIA symptoms at
      the time of dispatch and all cases with stroke/TIA symptoms identified on the
      scene by the ambulance personnel from November 2010 to May 2011. RESULTS: The
      study included 21760 cases: 18231 with stroke/TIA symptoms at dispatch and 9791
      with symptoms confirmed on the scene. The PPV of the dispatch stroke/TIA symptoms
      identification was 34.3% (95% CI 33.7-35.0; 6262/18231) and the sensitivity was
      64.0% (95% CI 63.0-64.9; 6262/9791). Centres using CPSS more often (>10% of
      cases) had both higher PPV (56%; CI 95% 57-60 vs 18%; CI 95% 17-19) and higher
      sensitivity (71%; CI 95% 87-89 vs 52%; CI 95% 51-54).In the multivariate
      regression a centre's CPSS use was associated with PPV (beta 0.48 p = 0.014) and
      negatively associated with sensitivity (beta -0.36; p = 0.063); centre
      sensitivity was associated with CPSS (beta 0.32; p = 0.002), adjusting for PPV.
      CONCLUSIONS: Centres that use CPSS more frequently during phone dispatch showed
      greater agreement with on-the-scene prehospital assessments, both in correctly
      identifying more cases with stroke/TIA symptoms and in giving fewer false
      positives for non-stroke/TIA cases. Our study shows an extreme variability in the
      performance among OCs, highlighting that form many centres there is room for
      improvement in both sensitivity and positive predictive value of the dispatch.
      Our results should be used for benchmarking proposals in the effort to identify
      best practices across the country.

PMID- 24330762
TI  - Post-operative acute kidney injury and five-year risk of death, myocardial
      infarction, and stroke among elective cardiac surgical patients: a cohort study.
AB  - INTRODUCTION: The prognostic impact of acute kidney injury (AKI) on long-term
      clinical outcomes remains controversial. We examined the five-year risk of death,
      myocardial infarction, and stroke after elective cardiac surgery complicated by
      AKI. METHODS: We conducted a cohort study among adult elective cardiac surgical
      patients without severe chronic kidney disease and/or previous heart or renal
      transplant surgery using data from population-based registries. AKI was defined
      by the Acute Kidney Injury Network (AKIN) criteria as a 50% increase in serum
      creatinine from baseline level, acute creatinine rise of >=26.5 MUmol/L (0.3
      mg/dL) within 48 hours, and/or initiation of renal replacement therapy within
      five days after surgery. We followed patients from the fifth post-operative day
      until myocardial infarction, stroke or death within five years. Five-year risk
      was computed by the cumulative incidence method and compared with hazards ratios
      (HR) from a Cox proportional hazards regression model adjusting for propensity
      score. RESULTS: A total of 287 (27.9%) of 1,030 patients developed AKI. Five-year
      risk of death was 26.5% (95% CI: 21.2 to 32.0) among patients with AKI and 12.1%
      (95% CI: 10.0 to 14.7) among patients without AKI. The corresponding adjusted HR
      of death was 1.6 (95% CI: 1.1 to 2.2). Five-year risk of myocardial infarction
      was 5.0% (95% CI: 2.9 to 8.1) among patients with AKI and 3.3% (95% CI: 2.1 to
      4.8) among patients without AKI. Five-year risk of stroke was 5.0% (95% CI: 2.8
      to 7.9) among patients with AKI and 4.2% (95% CI: 2.9 to 5.8) among patients
      without AKI. Adjusted HRs were 1.5 (95% CI: 0.7 to 3.2) of myocardial infarction
      and 0.9 (95% CI: 0.5 to 1.8) of stroke. CONCLUSIONS: AKI, within five days after
      elective cardiac surgery, was associated with increased five-year mortality and a
      statistically insignificant increased risk of myocardial infarction. No
      association was seen with the risk of stroke.

PMID- 24330763
TI  - MObile Technology for Improved Family Planning Services (MOTIF): study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: Providing women with contraceptive methods following abortion is
      important to reduce repeat abortion rates, yet evidence for effective post
      abortion family planning interventions are limited. This protocol outlines the
      evaluation of a mobile phone-based intervention using voice messages to support
      post-abortion family planning in Cambodia. METHODS/DESIGN: A single blind
      randomised controlled trial of 500 participants. Clients aged 18 or over,
      attending for abortion at four Marie Stopes International clinics in Cambodia,
      owning a mobile phone and not wishing to have a child at the current time are
      randomised to the mobile phone-based intervention or control (standard care) with
      a 1:1 allocation ratio.The intervention comprises a series of six automated voice
      messages to remind clients about available family planning methods and provide a
      conduit for additional support. Clients can respond to message prompts to request
      a phone call from a counsellor, or alternatively to state they have no problems.
      Clients requesting to talk to a counsellor, or who do not respond to the message
      prompts, receive a call from a Marie Stopes International Cambodia counsellor who
      provides individualised advice and support regarding family planning. The
      duration of the intervention is 3 months. The control group receive existing
      standard of care without the additional mobile phone-based support.We hypothesise
      that the intervention will remind clients about contraceptive methods available,
      identify problems with side effects early and provide support, and therefore
      increase use of post-abortion family planning, while reducing discontinuation and
      unsafe method switching.Participants are assessed at baseline and at 4 months.
      The primary outcome measure is use of an effective modern contraceptive method at
      4 months post abortion. Secondary outcome measures include contraception use,
      pregnancy and repeat abortion over the 4-month post-abortion period.Risk ratios
      will be used as the measure of effect of the intervention on the outcomes, and
      these will be estimated with 95% confidence intervals. All analyses will be based
      on the 'intention to treat' principle. DISCUSSION: This study will provide
      evidence on the effectiveness of a mobile phone-based intervention using voice
      messages to support contraception use in a population with limited literacy.
      Findings could be generalisable to similar populations in different settings.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01823861.

PMID- 24330764
TI  - Critical airway induced by formalin injection: case report.
AB  - BACKGROUND: Formalin is a saturated aqueous solution comprising 37-40 per cent
      formaldehyde. It is often used in histopathology laboratories as a tissue
      preservative. The ingestion or injection of formalin has an immediate, powerful
      and destructive impact on humans. This paper reports a case of formalin injection
      and reviews the relevant world literature. CASE REPORT: A 36-year-old male
      attempted suicide by injecting formalin into the right side of his neck,
      resulting in a critical airway situation. An endotracheal tube was inserted and a
      tracheostomy was then performed to secure his airway. After receiving medical
      treatment, including antibiotics and N-acetyl cysteine, the status of the
      patient's airway improved. CONCLUSION: When examining patients who have injected
      substances into their neck, the possibility of deep neck inflammation with airway
      compromise should be considered. Immediate management, which should include
      establishment of a definitive airway and prophylactic infection control, is
      crucial.

PMID- 24330765
TI  - VIRsiRNApred: a web server for predicting inhibition efficacy of siRNAs targeting
      human viruses.
AB  - BACKGROUND: Selection of effective viral siRNA is an indispensable step in the
      development of siRNA based antiviral therapeutics. Despite immense potential, a
      viral siRNA efficacy prediction algorithm is still not available. Moreover,
      performances of the existing general mammalian siRNA efficacy predictors are not
      satisfactory for viral siRNAs. Therefore, we have developed "VIRsiRNApred" a
      support vector machine (SVM) based method for predicting the efficacy of viral
      siRNA. METHODS: In the present study, we have employed a new dataset of 1725
      viral siRNAs with experimentally verified quantitative efficacies tested under
      heterogeneous experimental conditions and targeting as many as 37 important human
      viruses including HIV, Influenza, HCV, HBV, SARS etc. These siRNAs were divided
      into training (T1380) and validation (V345) datasets. Important siRNA sequence
      features including mono to penta nucleotide frequencies, binary pattern,
      thermodynamic properties and secondary structure were employed for model
      development. RESULTS: During 10-fold cross validation on T1380 using hybrid
      approach, we achieved a maximum Pearson Correlation Coefficient (PCC) of 0.55
      between predicted and actual efficacy of viral siRNAs. On V345 independent
      dataset, our best model achieved a maximum correlation of 0.50 while existing
      general siRNA prediction methods showed PCC from 0.05 to 0.18. However, using
      leave one out cross validation PCC was improved to 0.58 and 0.55 on training and
      validation datasets respectively. SVM performed better than other machine
      learning techniques used like ANN, KNN and REP Tree. CONCLUSION: VIRsiRNApred is
      the first algorithm for predicting inhibition efficacy of viral siRNAs which is
      developed using experimentally verified viral siRNAs. We hope this algorithm
      would be useful in predicting highly potent viral siRNA to aid siRNA based
      antiviral therapeutics development. The web server is freely available at
      http://crdd.osdd.net/servers/virsirnapred/.

PMID- 24330766
TI  - Effects of miR-193a and sorafenib on hepatocellular carcinoma cells.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a challenging malignancy of global
      importance, it is the third most common cause of cancer-related mortality
      worldwide. In the last years the multikinase inhibitor sorafenib has been used
      for advanced HCC, but some patients do not benefit from this therapy; thus, novel
      therapeutic options based on molecular approaches are urgently needed. microRNAs
      are short non coding RNAs involved in several physiological and pathological
      conditions including HCC and increasing evidence describes miRs as good tools for
      the molecular targeted therapies in HCC. The purpose of this study was to
      identify novel approaches to sensitize the HCC cells to sorafenib by microRNAs
      targeting urokinase-type plasminogen activator (uPA). METHODS: The miR-193a was
      validated as negative regulator of urokinase-type plasminogen activator (uPA) in
      2 HCC undifferentiated cell lines by transient transfection of miR and anti-miR
      molecules. The molecular interaction between miR-193a and uPA mRNA target was
      verified by luciferase reporter assay. The miR-193a expression level was
      evaluated by stem-loop real time PCR in tumoral tissues from 39 HCC patients. The
      HCC cells were co-treated with sorafenib and miR-193a and the effects on cellular
      proliferation, apoptosis were tested. The effect of sorafenib on c-met expression
      levels was assessed by western blotting. RESULTS: The miR-193a has resulted a
      negative regulator of uPA in both the HCC cell lines tested. The miR-193a
      expression has resulted dysregulated in tumoral tissues from 39 HCC patients. We
      found miR-193a down-regulation in HCC respect to peritumoral (PT) tissues and
      more in the cirrhotic HCCs than in non-cirrhotic ones. Transfection of HA22T/VGH
      HCC cells with miR-193a decreased proliferation and increased apoptosis, and
      combined treatment with miR-193a and sorafenib led to further proliferation
      inhibition. CONCLUSIONS: Our results present new advances in the post
      transcriptional miR-mediated mechanisms of uPA and they suggest a new strategy to
      impair the aggressive behavior of HCC cells. Our findings could be helpful to
      explore novel approaches for multi-target and multi-agent therapies of the HCC.

PMID- 24330767
TI  - Language and social/emotional problems identified at a universal developmental
      assessment at 30 months.
AB  - BACKGROUND: Preschool language and neurodevelopmental problems often persist and
      impede learning. The aims of the current study are to assess the uptake of a new
      universal 30 month health visitor contact and to quantify the prevalence of
      language delay and social/emotional difficulties. METHODS: All families of 30
      month old children in four Glasgow localities were offered a visit from their
      health visitor. Structured data were collected relating to language, social and
      emotional development using three instruments; The Strengths and Difficulties
      Questionnaire (SDQ), the abbreviated Sure Start Language Measure and a two-item
      language screen. RESULTS: From an eligible population of 543 children, there was
      a 90% return rate of contact forms from the health visitors, and assessments were
      completed on 78% of eligible children. Visit completion rates did not differ
      significantly by socio-economic status. 3-8% of children were reported to have
      language delay depending on the method of assessment. 8.8% of children scored in
      the "abnormal" range of SDQ total difficulties scores and 31.1% had an
      abnormality in at least one subscale. There was substantial overlap between
      language delay and abnormal scores on the SDQ. CONCLUSIONS: Universal assessment
      of neurodevelopmental function at 30 months identified a significant proportion
      of children, including those previously considered at low risk, with both
      language and social/emotional difficulties. Further work is required to assess
      the precise nature of these difficulties and to assess the potential impact on
      services.

PMID- 24330768
TI  - Mitral chordae myxoma-chordae replacement with a premeasured gore-tex loop using
      a minimally invasive video-assisted approach.
AB  - Cardiac myxomas are one of the most common types of primary cardiac tumors and
      are associated with embolization, angina, and sudden death. Most cardiac myxomas
      arise from the fossa ovalis, while those that arise from the mitral valve are
      exceedingly rare and those that arise from the chordae are even rarer. We report
      the case of a 28-year-old Caucasian woman who suffered from a brain infarction. A
      duplex ultrasound showed no cerebrovascular stenosis or occlusion, but an
      echocardiogram revealed a left ventricle pedunculated mobile mass (5 mm in
      diameter) that was attached to the mitral valve chordae tendineae. We elected
      cardiac surgery to resect the cardiac tumor and to avoid further embolic events.
      The traditional surgical strategy-mitral valve replacement through full
      sternotomy-has many disadvantages, particularly for young women. Therefore we
      desided to use the Premeasured Gore-Tex chordal loop method followed by
      annuloplasty using a minimally invasive video-assisted approach. Exploration of
      the mitral valve showed a globular tumor involving the anterior mitral leaflet
      chordae tendineae, which was removed along with the involved chordae tendineae.
      Histopathological examination of the tissue revealed a benign polypoid myxoma.
      The patient had an uneventful recovery and has remained symptom
      free.Echocardiography one week after surgery showed satisfactory valve function.
      We believe our surgical treatment was the most appropriate option for this case
      and it resulted in an excellent medical outcome and improved the quality of life,
      including only a small lateral scar without the need for teratogenic
      anticoagulants.

PMID- 24330769
TI  - Influence of acute kidney injury on short- and long-term outcomes in patients
      undergoing cardiac surgery: risk factors and prognostic value of a modified RIFLE
      classification.
AB  - INTRODUCTION: The development of acute kidney injury (AKI) is associated with
      poor outcome. The modified RIFLE (risk, injury, failure, loss of kidney function,
      and end-stage renal failure) classification for AKI, which classifies patients
      with renal replacement therapy needs according to RIFLE failure class, improves
      the predictive value of AKI in patients undergoing cardiac surgery. Our aim was
      to assess risk factors for post-operative AKI and the impact of renal function on
      short- and long-term survival among all AKI subgroups using the modified RIFLE
      classification. METHODS: We prospectively studied 2,940 consecutive
      cardiosurgical patients between January 2004 and July 2009. AKI was defined
      according to the modified RIFLE system. Pre-operative, operative and post
      operative variables usually measured on and during admission, which included main
      outcomes, were recorded together with cardiac surgery scores and ICU scores.
      These data were evaluated for association with AKI and staging in the different
      RIFLE groups by means of multivariable analyses. Survival was analyzed via Kaplan
      Meier and a risk-adjusted Cox proportional hazards regression model. A complete
      follow-up (mean 6.9 +/- 4.3 years) was performed in 2,840 patients up to April
      2013. RESULTS: Of those patients studied, 14% (n = 409) were diagnosed with AKI.
      We identified one intra-operative (higher cardiopulmonary bypass time) and two
      post-operative (a longer need for vasoactive drugs and higher arterial lactate 24
      hours after admission) predictors of AKI. The worst outcomes, including in
      hospital mortality, were associated with the worst RIFLE class. Kaplan-Meier
      analysis showed survival of 74.9% in the RIFLE risk group, 42.9% in the RIFLE
      injury group and 22.3% in the RIFLE failure group (P <0.001). Classification at
      RIFLE injury (Hazard ratio (HR) = 2.347, 95% confidence interval (CI) 1.122 to
      4.907, P = 0.023) and RIFLE failure (HR = 3.093, 95% CI 1.460 to 6.550, P =
      0.003) were independent predictors for long-term patient mortality. CONCLUSIONS:
      AKI development after cardiac surgery is associated mainly with post-operative
      variables, which ultimately could lead to a worst RIFLE class. Staging at the
      RIFLE injury and RIFLE failure class is associated with higher short- and long
      term mortality in our population.

PMID- 24330770
TI  - Pedigree and herd characterization of a donkey breed vulnerable to extinction.
AB  - Most donkey and local horse breeds are vulnerable to extinction as mechanization
      of agriculture progress throughout the world. The present study analyzed the
      pedigree and herd records of the donkey Asinina de Miranda breed (RAM),
      identifying genealogical and human factors that may affect the breed genetic
      diversity in the future and suggesting suitable strategies to breed preservation,
      early on the conservation program. The breeding rate was very low, with a ratio
      of foaling/live animals of 0.23 (178/760). The estimated number of founders and
      ancestors contributing to the reference population was 128 and 121. The number of
      founder herds in the reference population was 64, with an effective number of
      founder herds for the reference population of 7.6. The mean age of herd owners
      was 65.50 +/- 0.884 years, with a negative association among the herd size and
      owner's age (P<0.001). In contrast, the size of the herd and the ownership of a
      male were both positively associated (P<0.001) with the herd number of in-born
      foals. Both the owners' age and the herd location (RAM home region v. dispersal
      region) were negatively associated with the foaling number (P<0.001). The main
      identified risk factors were: low breeding rates; low number of males and their
      unequal contribution to the genetic pool; unequal contribution of the herds to
      genetic pool; and advanced age of herd owners.

PMID- 24330771
TI  - Pelvic inflammatory disease.
AB  - INTRODUCTION: Pelvic inflammatory disease is caused by infection of the upper
      female genital tract and is often asymptomatic. Pelvic inflammatory disease is
      the most common gynaecological reason for admission to hospital in the US, and is
      diagnosed in approximately 1% of women aged 16 to 45 years consulting their GP in
      England and Wales. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical questions: How do different antimicrobial
      regimens compare when treating women with confirmed pelvic inflammatory disease?
      What are the effects of routine antibiotic prophylaxis to prevent pelvic
      inflammatory disease before intrauterine contraceptive device (IUD) insertion? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to September 2013 (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), the European Medicines Agency (EMA), and the UK Medicines
      and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 13 RCTs or
      systematic reviews of 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: antibiotics (oral, parenteral, different
      durations, different regimens) and routine antibiotic prophylaxis (before
      intrauterine device insertion in women at high risk or low risk).

PMID- 24330772
TI  - Are phylogenetic trees suitable for chemogenomics analyses of bioactivity data
      sets: the importance of shared active compounds and choosing a suitable data
      embedding method, as exemplified on Kinases.
AB  - BACKGROUND: 'Phylogenetic trees' are commonly used for the analysis of
      chemogenomics datasets and to relate protein targets to each other, based on the
      (shared) bioactivities of their ligands. However, no real assessment as to the
      suitability of this representation has been performed yet in this area. We aimed
      to address this shortcoming in the current work, as exemplified by a kinase data
      set, given the importance of kinases in many diseases as well as the availability
      of large-scale datasets for analysis. In this work, we analyzed a dataset
      comprising 157 compounds, which have been tested at concentrations of 1 MUM and
      10 MUM against a panel of 225 human protein kinases in full-matrix experiments,
      aiming to explain kinase promiscuity and selectivity against inhibitors.
      Compounds were described by chemical features, which were used to represent
      kinases (i.e. each kinase had an active set of features and an inactive set).
      RESULTS: Using this representation, a bioactivity-based classification was made
      of the kinome, which partially resembles previous sequence-based classifications,
      where particularly kinases from the TK, CDK, CLK and AGC branches cluster
      together. However, we were also able to show that in approximately 57% of cases,
      on average 6 kinase inhibitors exhibit activity against kinases which are located
      at a large distance in the sequence-based classification (at a relative distance
      of 0.6 - 0.8 on a scale from 0 to 1), but are correctly located closer to each
      other in our bioactivity-based tree (distance 0 - 0.4). Despite this improvement
      on sequence-based classification, also the bioactivity-based classification
      needed further attention: for approximately 80% of all analyzed kinases, kinases
      classified as neighbors according to the bioactivity-based classification also
      show high SAR similarity (i.e. a high fraction of shared active compounds and
      therefore, interaction with similar inhibitors). However, in the remaining ~20%
      of cases a clear relationship between kinase bioactivity profile similarity and
      shared active compounds could not be established, which is in agreement with
      previously published atypical SAR (such as for LCK, FGFR1, AKT2, DAPK1, TGFR1,
      MK12 and AKT1). CONCLUSIONS: In this work we were hence able to show that (1)
      targets (here kinases) with few shared activities are difficult to establish
      neighborhood relationships for, and (2) phylogenetic tree representations make
      implicit assumptions (i.e. that neighboring kinases exhibit similar interaction
      profiles with inhibitors) that are not always suitable for analyses of
      bioactivity space. While both points have been implicitly alluded to before, this
      is to the information of the authors the first study that explores both points on
      a comprehensive basis. Excluding kinases with few shared activities improved the
      situation greatly (the percentage of kinases for which no neighborhood
      relationship could be established dropped from 20% to only 4%). We can conclude
      that all of the above findings need to be taken into account when performing
      chemogenomics analyses, also for other target classes.

PMID- 24330774
TI  - Use of a hooked cutting device compared with scissors for the emergency exposure
      of critically ill and injured patients.
AB  - INTRODUCTION: The initial assessment of critical patients includes prompt
      identification of life-threatening conditions. Any device or technique that can
      aid in this process may ultimately save lives. This study examined whether
      clothing could be removed faster with the use of a hooked cutting device as
      compared with the commonly-used heavy-duty, blunt-tipped, serrated scissors.
      METHODS: This study took place in an urban academic emergency department of a
      Level-1 trauma center. Human patient simulator mannequins were clothed in
      identical shirts and pants. The time required for clinical personnel to expose
      the patient using each device was measured. Each of the 50 participants was
      queried regarding their tactile comfort using each device. RESULTS: The mean time
      for shirt removal using scissors was 83 seconds (SD = 55 seconds; 95% CI, 68-99).
      The mean time for shirt removal using the hook device was 28 seconds (SD = 21
      seconds; 95% CI, 22-34). The mean time for pants removal using scissors was 69
      seconds (SD = 40 seconds; 95% CI, 56-73). The mean time for pants removal using
      the hook device was 19 seconds (SD=15 seconds; 95% CI, 15-23). CONCLUSIONS: The
      hooked device was 69% faster at removing clothing than traditionally-used
      scissors. Though simple in concept, these implications can be life saving,
      particularly in conditions of uncontrolled, life-threatening external hemorrhage.

PMID- 24330773
TI  - Immunomodulation targeting of both Abeta and tau pathological conformers
      ameliorates Alzheimer's disease pathology in TgSwDI and 3xTg mouse models.
AB  - BACKGROUND: Central to the pathogenesis of Alzheimer's disease (AD) and many
      other neurodegenerative diseases is the conformational change of a normal self
      protein into toxic oligomeric species and amyloid deposits. None of these
      disorders have an effective therapy, but immunization approaches hold great
      promise. We have previously shown that active immunization with a novel peptide
      when polymerized into a stable oligomeric conformation, pBri, induced a humoral
      immune response to toxic Abeta species in an AD model, APP/PS1 transgenic (Tg)
      mice, reducing plaque deposits. pBri is a glutaraldehyde polymerized form of the
      carboxyl fragment of an amyloidogenic protein, which is deposited in the brains
      of patients with a rare autosomal dominant disease due to a missense mutation in
      a stop codon, resulting in the translation of an intronic sequence, with no known
      sequence homology to any mammalian protein. METHODS: In the current study we
      tested whether pBri-peptide-based immunomodulation is effective at reducing both
      vascular amyloid deposits and tau-related pathology using TgSwDI mice with
      extensive congophilic angiopathy and 3xTg mice with tau pathology. RESULTS: Our
      results indicate that this immunomodulation approach, which produces a humoral
      response to proteins in a pathological conformation, is effective at reducing
      both Abeta and tau-related pathologies. CONCLUSIONS: This immunomodulatory
      approach has the advantage of using a non-self-immunogen that is less likely to
      be associated with autoimmune toxicity. Furthermore we found that it is able to
      target all the cardinal features of AD concurrently.

PMID- 24330775
TI  - Procalcitonin as a marker of sepsis and outcome in patients with neurotrauma: an
      observation study.
AB  - BACKGROUND: Procalcitonin (PCT) is a reliable biomarker of sepsis and infection.
      The level of PCT associated with sepsis and infection in patients with traumatic
      brain injury is currently unknown. The purpose of this study was to investigate
      the value of PCT and C-reactive protein (CRP) as diagnostic markers of sepsis and
      to evaluate the prognostic value of these markers related to the severity of
      injury, sepsis and mortality. METHODS: 105 adult patients with neurotrauma were
      enrolled in this study from June 2011 to February 2013. PCT and CRP were measured
      at admission and 2, 3, 5 and 7 days after admission. The sepsis criteria
      established by American College of Chest Physicians /Society of Critical Care
      Medicine Consensus Conference were used to identify patients. Injury Severity
      Score (ISS) and Glasgow Coma Score (GCS) were used to assess the severity of the
      injury. All these patients were monitored for 28 days. RESULTS: At admission, the
      median level of PCT was consistent with the severity of brain injury as follows:
      mild 0.08 ng/ml (0.05 - 0.13), moderate 0.25 ng/ml (0.11 - 0.55) and severe 0.31
      ng/ml (0.17 - 0.79), but the range of CRP levels varied greatly within the given
      severity of brain injury. Seventy-one (67.6%) patients developed sepsis. The
      initial levels of PCT at admission were statistically higher in patients with
      sepsis, compared with patients with systemic inflammatory response syndrome
      (SIRS), but there were no differences in the initial concentration of CRP between
      sepsis and SIRS. After adjusting for these parameters, multivariate logistic
      regression analysis revealed that PCT was an independent risk factor for septic
      complications (p < 0.05). The areas under the ROCs at admission for the
      prediction of mortality were 0.76 (p < 0.05) and 0.733 for PCT and CRP,
      respectively. CONCLUSIONS: Increased levels of PCT during the course of the ICU
      stay could be an important indicator for the early diagnosis of sepsis after
      neurotrauma. In addition, high serum levels of PCT in patients with neurotrauma
      at admission indicate an increased risk of septic complications, and the daily
      measurement of PCT assists in guiding antibiotic therapy in neurotrauma patients.

PMID- 24330776
TI  - Guided Application of Ventricular Catheters (GAVCA)--multicentre study to compare
      the ventricular catheter position after use of a catheter guide versus freehand
      application: study protocol for a randomised trail.
AB  - BACKGROUND: The standard technique for the placement of ventricular catheters
      (VC) comprises a high proportion of malpositioning of the catheter (12.5 to 40%).
      Technical advances such as neuronavigation or ultrasound have been shown to
      increase the accuracy of the procedure. Since these means result in significant
      technical and time consuming efforts, they are used for selected cases only. In
      order to simplify the controlled placement of ventricular catheters a newly
      developed smartphone assisted guiding tool has been introduced. In this study the
      efficacy and safety of this guiding tool is determined. METHODS/DESIGN: This
      study is a multicentre, randomised, controlled trial. A total of 144 patients
      planned for an elective shunting procedure will be enrolled throughout 10 study
      centres within two years. The primary objective of the trial is to show the
      superiority of the guided placement in comparison to the standard freehand
      technique of ventricular catheter application. Patients will be followed up for
      30 days after the operation in regard to image-based evaluation of the catheter
      position as well as possible shunt dysfunction and complications. DISCUSSION: The
      Guided Application of Ventricular Catheters (GAVCA) trial compares the guided
      catheter positioning with the standard freehand technique of catheter placement
      in hydrocephalic patients. If superiority is shown, the standard technique may be
      changed with the advantage of a more reliable and safer positioning of the
      ventricular catheter with just a slight effort in time and pre-operative
      planning. TRIAL REGISTRATION: The GAVCA trial is registered at ClinicalTrials.gov
      under the number NCT01811589.

PMID- 24330777
TI  - Proteomic analysis of surface proteins of Trichinella spiralis muscle larvae by
      two-dimensional gel electrophoresis and mass spectrometry.
AB  - BACKGROUND: Trichinella spiralis is a zoonotic tissue-dwelling parasitic nematode
      that infects humans and other mammals. Its surface proteins are recognized as
      antigenic in many infected hosts, being directly exposed to the host's immune
      system and are the main target antigens that induce the immune responses. The
      larval surface proteins may also interact with intestinal epithelial cells and
      may play an important role in the invasion and development process of T.
      spiralis. The purpose of this study was to analyze and characterize the surface
      proteins of T. spiralis muscle larvae by two-dimensional gel electrophoresis (2
      DE) and mass spectrometry. METHODS: The surface proteins of T. spiralis muscle
      larvae were stripped from the cuticle of live larvae by the
      cetyltrimethylammonium bromide (CTAB) and sodium deoxycholate. The surface
      protein stripping was examined by an immunofluorescent test (IFT). The surface
      proteins were analyzed by SDS-PAGE and Western blotting, and then identified by 2
      DE and MALDI-TOF/TOF mass spectrometry analysis. RESULTS: The IFT results showed
      that the surface proteins-stripped larvae were not recognized by sera of mice
      immunized with surface antigens. Western blotting showed 7 of 12 protein bands of
      the surface proteins were recognized by mouse infection sera at 18 dpi and at 42
      dpi. The 2-DE results showed that a total of approximately 33 proteins spots were
      detected with molecular weights varying from 10 to 66 kDa and isoelectric point
      (pI) from 4 to 7. Twenty-seven of 33 protein spots were identified and
      characterized to correlate with 15 different proteins. Out of the 14 proteins
      identified as T. spiralis proteins, 5 proteins (partial P49 antigen,
      deoxyribonuclease II family protein, two serine proteases, and serine proteinase)
      had catalytic and hydrolase activity. All of these 5 proteins were also
      associated with metabolic processes and 2 of the five proteins were associated
      with cellular processes. CONCLUSIONS: In this study, T. spiralis muscle larval
      surface proteins have been identified, which will provide useful information to
      elucidate the host-parasite interaction, identify the invasion-related proteins,
      early diagnostic antigens and the targets for a vaccine.

PMID- 24330778
TI  - Different loss of material in recurrent chromosome 20 interstitial deletions in
      Shwachman-Diamond syndrome and in myeloid neoplasms.
AB  - BACKGROUND: An interstitial deletion of the long arms of chromosome 20,
      del(20)(q), is frequent in the bone marrow (BM) of patients with myelodysplastic
      syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms
      (MPN), and it is recurrent in the BM of patients with Shwachman-Diamond syndrome
      (SDS), who have a 30-40% risk of developing MDS and AML. RESULTS: We report the
      results obtained by microarray-based comparative genomic hybridization (a-CGH) in
      six patients with SDS, and we compare the loss of chromosome 20 material with one
      patient with MDS, and with data on 92 informative patients with MDS/AML/MPN and
      del(20)(q) collected from the literature. CONCLUSIONS: The chromosome material
      lost in MDS/AML/MPN is highly variable with no identifiable common deleted
      regions, whereas in SDS the loss is more uniform: in 3/6 patients it was almost
      identical, and the breakpoints that we defined are probably common to most
      patients from the literature. In some SDS patients less material may be lost, due
      to different distal breakpoints, but the proximal breakpoint is in the same
      region, always leading to the loss of the EIF6 gene, an event which was related
      to a lower risk of MDS/AML in comparison with other patients.

PMID- 24330779
TI  - A methodological survey of the analysis, reporting and interpretation of Absolute
      Risk ReductiOn in systematic revieWs (ARROW): a study protocol.
AB  - BACKGROUND: Clinicians, providers and guideline panels use absolute effects to
      weigh the advantages and downsides of treatment alternatives. Relative measures
      have the potential to mislead readers. However, little is known about the
      reporting of absolute measures in systematic reviews. The objectives of our study
      are to determine the proportion of systematic reviews that report absolute
      measures of effect for the most important outcomes, and ascertain how they are
      analyzed, reported and interpreted. METHODS/DESIGN: We will conduct a
      methodological survey of systematic reviews published in 2010. We will conduct a
      1:1 stratified random sampling of Cochrane vs. non-Cochrane systematic reviews.
      We will calculate the proportion of systematic reviews reporting at least one
      absolute estimate of effect for the most patient-important outcome for the
      comparison of interest. We will conduct multivariable logistic regression
      analyses with the reporting of an absolute estimate of effect as the dependent
      variable and pre-specified study characteristics as the independent variables.
      For systematic reviews reporting an absolute estimate of effect, we will document
      the methods used for the analysis, reporting and interpretation of the absolute
      estimate. DISCUSSION: Our methodological survey will inform current practices
      regarding reporting of absolute estimates in systematic reviews. Our findings may
      influence recommendations on reporting, conduct and interpretation of absolute
      estimates. Our results are likely to be of interest to systematic review authors,
      funding agencies, clinicians, guideline developers and journal editors.

PMID- 24330780
TI  - Microrna-124 targets flotillin-1 to regulate proliferation and migration in
      breast cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) have been documented as playing important roles in
      cancer development. In this study, we investigated the role of miR-124 in breast
      cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124. METHODS:
      The expression levels of miR-124 were examined in breast cancer cell lines and
      patient specimens using quantitative reverse transcription-PCR. The
      clinicopathological significance of the resultant data was later analyzed. Next,
      we explored the function of miR-124 to determine its potential roles on cancer
      cell growth and migration in vitro. A luciferase reporter assay was conducted to
      confirm the target gene of miR-124, and the results were validated in cell lines
      and patient specimens. RESULTS: We found that miR-124 expression was
      significantly downregulated in breast cancer cell lines and patient specimen
      compared with normal cell lines and paired adjacent normal tissues (P < 0.0001),
      respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage
      (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines,
      the ectopic expression of miR-124 inhibited cell growth and migration in vitro.
      Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and
      miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays
      confirmed that miR-124 could directly bind to the 3' untranslated region of FLOT1
      and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely
      correlated with miR-124 in breast cancer tissues. Consistent with the effect of
      miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth
      and migration. We also observed that the rescue expression of FLOT1 partially
      restored the effects of miR-124. CONCLUSIONS: Our study demonstrated that miR-124
      might be a tumor suppressor in breast cancer via the regulation of FLOT1. This
      microRNA could serve as a potential diagnostic marker and therapeutic target for
      breast cancer.

PMID- 24330781
TI  - Bridging evidence-practice gaps: improving use of medicines in elderly Australian
      veterans.
AB  - BACKGROUND: The Australian Government Department of Veterans' Affairs (DVA) funds
      an ongoing health promotion based program to improve use of medicines and related
      health services, which implements interventions that include audit and feedback
      in the form of patient-specific feedback generated from administrative claims
      records. We aimed to determine changes in medicine use as a result of the
      program. METHODS: The program provides targeted patient-specific feedback to
      medical practitioners. The feedback is supported with educational material
      developed by a clinical panel, subject to peer review and overseen by a national
      editorial committee. Veterans who meet target criteria also receive educational
      brochures. The program is supported by a national call centre and ongoing
      national consultation. Segmented regression analyses (interrupted time series)
      were undertaken to assess changes in medication use in targeted veterans pre and
      post each intervention. RESULTS: 12 interventions were included; three to
      increase medicine use, seven which aimed to reduce use, and two which had
      combination of messages to change use. All programs that aimed to increase
      medicine use were effective, with relative effect sizes at the time of the
      intervention ranging from 1% to 8%. Mixed results were seen with programs aiming
      to reduce inappropriate medicine use. Highly specific programs were effective,
      with relative effect sizes at the time of the intervention of 10% decline in use
      of NSAIDs in high risk groups and 14% decline in use of antipsychotics in
      dementia. Interventions targeting combinations of medicines, including medicine
      interactions and potentially inappropriate medicines in the elderly did not
      change practice significantly. Interventions with combinations of messages
      targeting multiple components of practice had an impact on one component, but not
      all components targeted. CONCLUSIONS: The Veterans' MATES program showed positive
      practice change over time, with interventions increasing use of appropriate
      medicines where under-use was evident and reduced use of inappropriate medicines
      when single medicines were targeted. Combinations of messages were less
      effective, suggesting specific messages focusing on single medicines are required
      to maximise effect. The program provides a model that could be replicated in
      other settings.

PMID- 24330782
TI  - Dietary hyperoxaluria is not reduced by treatment with lactic acid bacteria.
AB  - BACKGROUND: Secondary hyperoxaluria either based on increased intestinal
      absorption of oxalate (enteric), or high oxalate intake (dietary), is a major
      risk factor of calcium oxalate urolithiasis. Oxalate-degrading bacteria might
      have beneficial effects on urinary oxalate excretion resulting from decreased
      intestinal oxalate concentration and absorption. METHODS: Twenty healthy subjects
      were studied initially while consuming a diet normal in oxalate. Study
      participants were then placed on a controlled oxalate-rich diet for a period of 6
      weeks. Starting with week 2 of the oxalate-rich diet, participants received 2.6
      g/day of a lactic acid bacteria preparation for 5 weeks. Finally, subjects were
      examined 4 weeks after treatment while consuming again a normal-oxalate diet.
      Participants provided weekly 24-hour urine specimens. Analyses of blood samples
      were performed before and at the end of treatment. RESULTS: Urinary oxalate
      excretion increased significantly from 0.354 +/- 0.097 at baseline to 0.542 +/-
      0.163 mmol/24 h under the oxalate-rich diet and remained elevated until the end
      of treatment, as did relative supersaturation of calcium oxalate. Plasma oxalate
      concentration was significantly higher after 5 weeks of treatment compared to
      baseline. Four weeks after treatment, urinary oxalate excretion and relative
      supersaturation of calcium oxalate fell to reach initial values. CONCLUSIONS:
      Persistent dietary hyperoxaluria and increased plasma oxalate concentration can
      already be induced in healthy subjects without disorders of oxalate metabolism.
      The study preparation neither reduced urinary oxalate excretion nor plasma
      oxalate concentration. The preparation may be altered to select for lactic acid
      bacteria strains with the highest oxalate-degrading activity.

PMID- 24330783
TI  - Healthy incentive scheme in the Irish full-day-care pre-school setting.
AB  - A pre-school offering a full-day-care service provides for children aged 0-5
      years for more than 4 h/d. Researchers have called for studies that will provide
      an understanding of nutrition and physical activity practices in this setting.
      Obesity prevention in pre-schools, through the development of healthy
      associations with food and health-related practices, has been advocated. While
      guidelines for the promotion of best nutrition and health-related practice in the
      early years' setting exist in a number of jurisdictions, associated regulations
      have been noted to be poor, with the environment of the child-care facility
      mainly evaluated for safety. Much cross-sectional research outlines poor
      nutrition and physical activity practice in this setting. However, there are few
      published environmental and policy-level interventions targeting the child-care
      provider with, to our knowledge, no evidence of such interventions in Ireland.
      The aim of the present paper is to review international guidelines and
      recommendations relating to health promotion best practice in the pre-school
      setting: service and resource provision; food service and food availability; and
      the role and involvement of parents in pre-schools. Intervention programmes and
      assessment tools available to measure such practice are outlined; and insight is
      provided into an intervention scheme, formulated from available best practice,
      that was introduced into the Irish full-day-care pre-school setting.

PMID- 24330784
TI  - The ascending aortic image quality and the whole aortic radiation dose of high
      pitch dual-source CT angiography.
AB  - BACKGROUND: Aortic dissection is a lift-threatening medical emergency associated
      with high rates of morbidity and mortality. The incidence rate of aortic
      dissection is estimated at 5 to 30 per 1 million people per year. The prompt and
      correct diagnosis of aortic dissection is critical. This study was to compare the
      ascending aortic image quality and the whole aortic radiation dose of high-pitch
      dual-source CT angiography and conventional dual-source CT angiography. METHODS:
      A total of 110 consecutive patients with suspected aortic dissection and other
      aortic disorders were randomly divided into two groups. Group A underwent
      traditional scan mode and Group B underwent high-pitch dual-source CT scan mode.
      The image quality and radiation dose of two groups were compared. RESULTS: Close
      interobserver agreement was found for image quality scores (kappa = 0.87). The
      image quality of ascending aorta was significantly better in the high-pitch group
      than in the conventional group (2.78 +/- 0.46 vs 1.57 +/- 0.43, P < 0.001). There
      was no significant difference of the CT attenuation values, the aortic image
      noise and SNR between two groups. The mean radiation dose of high-pitch group was
      also significantly lower than that of conventional group (2.7 +/- 0.6 mSv vs. 3.9
      +/- 0.9 mSv, P < 0.001). CONCLUSIONS: High-pitch dual-source CT angiography of
      the whole aorta can provide motion-artifact-free imaging of the ascending aorta
      at a low radiation dose compared to conventional protocol.

PMID- 24330785
TI  - Comparative Labeling of Equine and Ovine Multipotent Stromal Cells With
      Superparamagnetic Iron Oxide Particles for Magnetic Resonance Imaging In Vitro.
AB  - The purpose of this study was to evaluate the use of three different
      superparamagnetic iron oxide (SPIO) particles for labeling of ovine and equine
      bone marrow (BM)-derived multipotent stromal cells (MSCs) in vitro. MSCs were
      obtained from five adult sheep and horses, respectively. After three passages
      (p3), cells were labeled with either 1) Molday ION Rhodamine B, 2) Endorem, 3)
      Resovist, or 4) remained unlabeled as control. Labeling efficiency, marker
      retention, and long-term detectability in MRI until p7 were evaluated. Further,
      proliferation capacity and trilineage differentiation as indicators for potential
      impact on stromal cell characteristics were assessed. MSCs of both species were
      successfully labeled with all three SPIO products. A high, exclusively
      intracellular, iron uptake was achieved by Molday ION Rhodamine B only. Labeling
      with Resovist led to prominent extracellular iron presence; labeling with Endorem
      was less efficient. During MRI, all labeled cells showed strong hypointense
      signals, contrary to unlabeled controls. Resovist induced the largest areas of
      hypointense signals, followed by Molday ION Rhodamine B and Endorem. MRI signal
      detectability decreased from p4 to p7. Proliferation, adipogenic, and osteogenic
      differentiation potential were not reduced by cell labeling compared to unlabeled
      cells. Chondrogenic differentiation capacity decreased with increasing amount of
      iron associated with the cells. Among the three products, Resovist and Molday
      were identified as promising labeling agents. While Resovist achieved superior
      results in most of the assessed parameters, Molday ION Rhodamine B ensured
      intracellular iron uptake without extracellular SPIO complexes and consistent
      hypointense signals on MRI. 

PMID- 24330786
TI  - [Population screening: there are no certainties].
AB  - Massive investments are being made for research into the prevention and reduction
      of risks and diseases. False-positive outcomes from screening investigations
      result in fear in a substantial number of patients, and are expensive for society
      as a whole. Screening for breast cancer has little or no impact on breast-cancer
      mortality; rather, the negative side-effects of false-positive outcomes of breast
      cancer screening are a serious problem. The incidence of false-positive results
      of colorectal cancer screening is underestimated. The risks of overdiagnosis and
      overtreatment as a result of screening are substantial. 

PMID- 24330787
TI  - [Tetanus prophylaxis after an injury; check the need for vaccination and
      immunoglobulin].
AB  - Tetanus can occur after an injury and is caused by the exotoxin of Clostridium
      tetani. Characteristics of generalised tetanus include spasms in the back and
      other muscles, trismus, risus sardonicus and difficulty in breathing caused by
      laryngospasms. Vaccination through the National Vaccination Programme of the
      Netherlands has resulted in 94% of the population being protected against
      tetanus; certain groups, however, have a low rate of vaccination. In the
      Netherlands, 5 patients were reported to have generalised tetanus in 2011. This
      figure is relatively high in comparison with previous years. Of these 5 patients,
      3 did not receive post-exposure-prophylaxis (PEP) after their injuries, or
      received it incompletely. PEP may be comprised of 1 or more vaccinations with the
      tetanus toxoid and/or the administration of tetanus immunoglobulin. Patients who
      have sustained an injury should be evaluated in accordance with the guideline
      'Tetanus' by the Landelijke Coordinatie Infectieziekten (National Coordination
      Centre for communicable disease control), and to assess whether PEP is indicated.

PMID- 24330788
TI  - [Five years of European regulation on medication use in children: what has been
      achieved?].
AB  - It is not known if many existing medications can safely be used in children. For
      this reason the EU Paediatric Regulation came into force in 2007. When new
      medications are developed, pharmaceutical companies are obliged to produce a plan
      to research their use in children which must be approved by the regulatory
      authorities. Existing data on medications also had to be submitted. Review took
      place five years after the introduction of this regulation: of 682 medications,
      476 plans were approved. In 206 of these medications this was unnecessary. By the
      end of 2011, research into 29 medications had been completed. The use of 10 of
      the 113 new, previously unregistered medications in children was approved, as was
      the case with 30 registered medications. Examination of existing data shows that
      results are often limited to changes in the 'Summary of Product Characteristics'.
      Many planned studies still have to be wound up, but in time the amount of
      information on safety and efficacy of new medications in children will increase
      greatly. 

PMID- 24330790
TI  - [Developments in corneal transplants: lamellar techniques emerging].
AB  - Corneal transplants are the most frequently performed human transplant procedure.
      In the last decade, we have seen large developments in the field of corneal
      transplant surgery. Currently, several techniques are being used in the
      Netherlands, each with its own advantages and disadvantages and with distinct
      indications. In penetrating keratoplasty all layers of the cornea are replaced by
      a donor cornea. In so-called lamellar corneal transplantation only the affected
      layer of the cornea is replaced by donor tissue. The developments in corneal
      transplantation surgery have resulted in an improved prognosis in terms of vision
      and fewer complications.

PMID- 24330791
TI  - [Intra-uterine death caused by fetal akinesia].
AB  - BACKGROUND: When two successive pregnancies end in intra-uterine fetal death
      (IUFD), the question of whether it is coincidental or if there is an underlying
      abnormality arises. Although diagnostic investigations into the underlying cause
      are not always carried out after IUFD, they are recommended by the professional
      body. CASE DESCRIPTION: A 28-year-old female attended our gynaecology outpatient
      clinic for a second opinion following two intra-uterine fetal deaths. Her own
      treating physician was of the opinion that there was no connection between the
      two IUFDs. After a multidisciplinary evaluation, the phenotype fetal akinesia
      deformation sequence (FADS) was diagnosed in both cases. This is a rare,
      clinically and aetiologically heterogeneous group of disorders. Thereafter the
      patient and her husband were offered specific pre-conception counseling.
      CONCLUSION: Every IUFD justifies systemic and multidisciplinary investigation to
      determine any underlying aetiology such as FADS. This may contribute to better
      pre-conception advice and prenatal individualised diagnostics in a subsequent
      pregnancy.

PMID- 24330792
TI  - [A woman with a pigmentation of the hard palate].
AB  - A bluish flat pigmented lesion of the hard palate of a 51-year-old woman was
      excised to exclude malignancy, in particular oral malignant melanoma. On
      histopathological examination, depositions of black pigment were seen accompanied
      by several foreign body giant cells. Probably due to a childhood trauma, a pencil
      point had penetrated the hard palate. 

PMID- 24330793
TI  - [Considerations when using creatinine as a measure of kidney function].
AB  - Reported serum creatinine concentrations can sometimes vary considerably, even
      when the renal function does less so or even not. This variation is partly due to
      true changes in actual serum concentration, and partly due to interferences in
      the measurement technique, thus not reflecting a true change in concentration.
      Increased or decreased endogenous creatinine production, ingested creatinine
      sources through meat eating or certain creatine formulations, and interference by
      either browning of chromogenic substances in Jaffe measurement techniques or
      promotors and inhibitors of enzymatic reaction methods do play a role. Reliable
      serum creatinine measurements are needed for renal function estimating equations.
      In screening circumstances and daily practice, chronic kidney disease staging is
      based on these estimated glomerular filtration rate values. Given the possible
      influences on reported serum creatinine concentrations, it is important for
      health care workers to remain critical when interpreting outcomes of renal
      function estimating equations and to not see every reported result based on an
      equation as a true reflection of renal function. 

PMID- 24330794
TI  - [Neurological signs in aortic dissection].
AB  - A substantial number of patients suffering from aortic dissection will show
      neurological signs. These can dominate the clinical picture and hinder an
      accurate diagnosis of this life-threatening disease. We present a case of lower
      extremity pain and a case of transient global amnesia caused by aortic
      dissection. A third patient suffered from acute cerebral ischemia accompanied by
      hypotension and back pain, suggestive of aortic dissection. In this third case,
      aortic dissection was excluded before systemic thrombolytic therapy was
      administered, for the patient could have suffered disastrous complications caused
      by this emergency stroke therapy. Clinicians should be aware that a wide range of
      cerebral, spinal and peripheral neurological signs can be caused by aortic
      dissection. An unusual combination of symptoms can be a clue for underlying
      aortic disease. High-risk clinical features are predisposing factors in medical
      history, typical acute onset back or chest pain, and pulse deficit, blood
      pressure asymmetry or a new cardiac murmur on physical examination. These
      features should be explicitly evaluated in patients with an acute neurological
      deficit. If neurological symptoms and a high-risk clinical feature are present,
      immediate aortic imaging should be considered since early detection can be life
      saving. 

PMID- 24330796
TI  - [Intra-arterial treatment of ischemic stroke--still no evidence but reason for
      further study].
AB  - In 3 recent randomized controlled trials of intra-arterial treatment of acute
      ischemic stroke - IMS-III, SYNTHESIS and MR RESCUE - intra-arterial treatment
      increased the proportion of patients with recanalization and the treatment
      appeared safe. However, the trials did not show an effect on functional recovery,
      although a substantial effect could not be excluded. The delay between onset of
      symptoms and treatment was long, and stent retrievers were used in only a few
      patients. In our view, a rational and ethical approach would now be to treat
      quickly with IV rtPA and when possible, refer and include in new randomized
      clinical trials that compare intra-arterial treatment with standard care, such as
      MR CLEAN or BASICS in the Netherlands. 

PMID- 24330797
TI  - [The diagnostic benefits of lipase values in acute pancreatitis].
AB  - Serum lipase is a biochemical marker used for diagnosing acute pancreatitis.
      Lipase has largely replaced amylase in terms of diagnostic value, although both
      markers are still commonly used. In this publication, we discuss the diagnostic
      superiority of lipase compared to amylase in acute pancreatitis. Two cases are
      discussed; both patients presented with elevated lipase values but due to
      different causes. The first patient, who had recently experienced cholecystitis,
      presented to the emergency room with abdominal pain and high lipase levels. The
      second patient, who had received a renal transplant a few years earlier, visited
      the gastroenterological outpatient clinic with abdominal pain and only a slightly
      elevated lipase level. 

PMID- 24330798
TI  - [Surgical complications in elderly patients with breast cancer].
AB  - Old age is strongly associated with comorbidity and decreased functioning, which
      in turn affects treatment decisions for elderly breast cancer patients. In recent
      years, the rate of elderly patients with breast cancer who were not operated on
      has increased considerably. Older age and an increased number of concomitant
      diseases are associated with an increased risk of postoperative complications.
      Mortality is higher in patients who experience complications than in patients who
      do not. The death of a patient who experiences a complication does not result
      from the complication itself; rather, it is associated with factors that make
      such a patient vulnerable e.g. comorbidity and poor functional status. Hormonal
      therapy could be a good alternative for surgical treatment in vulnerable elderly
      patients, but sound research into this is lacking. Deciding against the surgical
      treatment of elderly patients with breast cancer based on the fear of
      postoperative mortality is not justifiable; however, there is too little evidence
      on the consequences of breast cancer surgery on outcome measures such as quality
      of life and functional status yet available to be able to offer strong
      recommendations on the surgical treatment of elderly patients with breast cancer.

PMID- 24330799
TI  - [Important changes in the Dutch College of General Practitioners (NHG) practice
      guideline 'Atrial fibrillation': revised practice guideline issued].
AB  - A small number of points in the NHG practice guideline 'Atrial fibrillation' have
      been reviewed; this has important consequences for general practice. The risk of
      ischaemic CVA in patients with atrial fibrillation is determined using a new risk
      score (CHA2DS2-VASc). The target value of the resting ventricular frequency has
      been increased from a maximum of 90 to a maximum of 110 beats per minute. Oral
      anticoagulants are indicated in almost all patients aged 65 years and older with
      atrial fibrillation; the only group in whom antithrombotic medication is not
      indicated is men under the age of 75 with no cardiovascular comorbidity.
      Acetylsalicylic acid for the prevention of thrombo-embolism is only indicated if
      oral anticoagulants are contra-indicated. The new oral anticoagulants (NOACs)
      have very limited use in the prevention of a thrombo-embolism in general
      practice.

PMID- 24330800
TI  - [Never give negative pregnancy advice].
AB  - Many doctors still tell some patients that a (subsequent) pregnancy is
      contraindicated. Aside from the fact that the desire to have a (or another) child
      is often extremely strong, which often results in ignoring the message, this type
      of advice may have serious negative consequences. Women at high risk of
      cardiovascular complications may decide to delay in making their first
      appointment to avoid an angry doctor who might push them towards an abortion.
      Women may postpone a subsequent pregnancy out of fear of preeclampsia, while this
      in fact increases the recurrence risk. Doctors often scare patients with stories
      about drugs causing fetal anomalies, while only a small minority of drugs, and
      then only during a limited time in pregnancy, are truly teratogenic. Prepregnancy
      counselling should involve a well-informed, balanced discussion on risks, while
      acknowledging a woman's desire for childbearing and ensuring that she will
      receive all possible support when she does become pregnant. 

PMID- 24330801
TI  - Waterworks, a full-scale chemical exposure exercise: interrogating pediatric
      critical care surge capacity in an inner-city tertiary care medical center.
AB  - INTRODUCTION: Pediatric Intensive Care Unit (PICU) resources are overwhelmed in
      disaster as the need to accommodate influx of critically-ill children is
      increased. A full-scale chlorine overexposure exercise was conducted by the New
      York Institute for All Hazard Preparedness (NYIAHP) to assess the appropriateness
      of response of Kings County Hospital Center's (KCHC's) PICU surge plan to an
      influx of critically-ill children. The primary endpoint that was assessed was the
      ability of the institution to follow the PICU surge plan, while secondary
      endpoints include the ability to provide appropriate medical management. METHODS:
      Thirty-six actors/patients (medical students or emergency medicine residents)
      were educated on presentations and appropriate medical management of patients
      after a chlorine overexposure, as well as lectures on drill design and expected
      PICU surge response. Victims presented to the hospital after simulated accidental
      chlorine overexposure at a public pool. Twenty-two patients with 14 family
      members needed evaluation; nine of these patients would require PICU admission.
      Three of nine PICU patients were low-fidelity mannequins. In addition to the 36
      actor/patient evaluators, each area had two to four expert evaluators (disaster
      preparedness experts) to assess appropriateness of global response. Patients were
      expected to receive standard of care. Appropriateness of medical decisions and
      treatment was assessed retrospectively with review of electronic medical record.
      RESULTS: The initial PICU census was three of seven; two of these patients were
      transferred to the general ward. Of the nine patients that required Intensive
      Care Unit (ICU) admission, six actor/patients were admitted to the PICU, one was
      admitted to the Surgical Intensive Care Unit (SICU), one went to the Operating
      Room (OR), and one was admitted to a monitored-surge general pediatric bed. The
      remaining 13 actor/patients were treated and released. Medical, nursing, and
      respiratory staffing in the PICU and the general ward were increased by two main
      mechanisms (extension of work hours and in-house recruitment of additional
      staff). Emergency Department (ED) staffing was artificially increased prior to
      the drill. With the exception of ocular fluid pH testing in patients with ocular
      pruritus, all necessary treatments were given; however, an unneeded albuterol
      treatment was administered to one patient. Chart review showed adequate discharge
      instructions in four of 13 patients. Nine patients without respiratory complaints
      in the ED were not instructed to observe for dyspnea. All patients were in the
      PICU or alternate locations within 90 minutes. Discussion The staff was well
      versed in the major details of KCHC's PICU surge plan, which allowed smooth
      transition of patient care from the ED to the PICU. The plan provided for a
      roadmap to achieve adequate medical, nursing, and respiratory therapists. Medical
      therapy was appropriate in the PICU; however, in the ED, patients with ocular
      complaints did not receive optimal care. In addition, written discharge
      instruction and educational material regarding chlorine overexposure to all
      patients were not consistently provided. The PICU surge plan was immediately
      accessible through the KCHC intranet; however, not all participants were
      cognizant of this fact; this decreased the efficiency with which the roadmap was
      followed. An exaggerated ED staff facilitated evaluation and transfer of
      patients. CONCLUSION: During disasters, the ability to surge is paramount and
      each hospital addresses it differently. Hospitals and departments have written
      surge plans, but there is no literature available which assesses the validity of
      said plans through a rigorous, structured, simulated disaster drill. This study
      is the first to assess validity and effectiveness of a hospital's PICU surge
      plan. Overall, the KCHC PICU surge plan was effective; however, several
      deficiencies (mainly in communication and patient education in the ED) were
      identified, and this will improve future response.

PMID- 24330802
TI  - Virucidal activity of Formulation I of the World Health Organization's alcohol
      based handrubs: impact of changes in key ingredient levels and test parameters.
AB  - BACKGROUND: A recently modified World Health Organization (WHO) Formulation I was
      examined as 80% and 97% solutions against poliovirus type 1, adenovirus type 5
      and murine norovirus according to the new European Norm prEN 14476:2011. In a
      previous study the unmodified WHO Formulation I had failed to demonstrate a
      sufficient activity against poliovirus type 1 according to the European Norm EN
      14476-2007 whereas a sufficient activity was seen with adeno- and norovirus.
      FINDINGS: The modified WHO Formulation I demonstrated a virucidal activity
      against all 3 test viruses of the European Norm prEN 14476:2011 under clean
      conditions. This was achieved as 80% solution against adeno- and norovirus within
      30 seconds and as 97% solution against poliovirus within 60 seconds. Testing the
      unmodified WHO Formulation I against poliovirus type 1 in the 97% assay of the
      European Norm prEN 14476:2011 an identical activity could be demonstrated. When
      comparing the 80% and the 97% assay of the European Norm prEN 14476:2011 the
      modified WHO Formulation I as 80% solution was active against adenovirus type 5
      within 30 seconds whereas the 97% solution failed within 2 minutes exposure time.
      CONCLUSIONS: The technical possibility in the new European Norm prEN 14476:2011
      allows testing a ready-to-use disinfectant as 97% solution and is responsible for
      the new virucidal claim of the modified WHO Formulation I. In contrast to the
      improvements with poliovirus type 1 the activity against adenovirus type 5
      decreased when increasing the test concentration from 80% to 97%.

PMID- 24330803
TI  - On-farm animal welfare assessment in beef bulls: consistency over time of single
      measures and aggregated Welfare Quality((r)) scores.
AB  - Consistency over time of (on-farm) animal welfare assessment systems forms part
      of reliability, meaning that results of the assessment should be representative
      of the longer-term welfare state of the farm as long as the housing and
      management conditions have not changed considerably. This is especially important
      if assessments are to be used for certification purposes. It was the aim of the
      present study to investigate consistency over time of the Welfare Quality((r))
      (WQ((r))) assessment system for fattening cattle at single measure level,
      aggregated criterion and principle scores, and overall classification across
      short-term (1 month) and longer-term periods (6 months). We hypothesized that
      consistency over time of aggregated criterion and principle scores is higher than
      that of single measures. Consistency was also expected to be lower with longer
      intervals between assessments. Data were obtained using the WQ((r)) protocol for
      fattening cattle during three visits (months 0, 1 and 7) on 63 beef farms in
      Austria, Germany and Italy. Only data from farms where no major changes in
      housing and management had taken place were considered for analysis. At the
      single measure level, Spearman rank correlations between visits were >0.7 and
      variance was lower within farms than between farms for six and two of 19 measures
      after 1 month and 6 months, respectively. After aggregation of single measures
      into criterion and principle scores, five and two of 10 criteria and three and
      one of four principles were found reliable after 1 and 6 months, respectively. At
      the WQ((r)) principle level, this was the case for three and one of four
      principles. Seventy-nine per cent and 75% of the farms were allocated to the same
      overall welfare category after 1 month and 6 months. Possible reasons for a lack
      of consistency are seasonal effects or short-term fluctuations that occur under
      normal farm conditions, low prevalence of clinical measures and probably
      insufficient sample size, whereas poor inter-observer agreement leading to
      inflation of correlation can be ruled out. At the criterion and principle level,
      aggregation of information into scores appears to partly smoothen undirected
      variation at the single measure level without losing sensitivity in terms of
      welfare evaluation. Reliable on-farm animal welfare assessments should therefore
      be based on repeated assessments. Further long-term studies are recommended to
      better understand the factors influencing consistency over time.

PMID- 24330804
TI  - Persistently high venous-to-arterial carbon dioxide differences during early
      resuscitation are associated with poor outcomes in septic shock.
AB  - INTRODUCTION: Venous-to-arterial carbon dioxide difference (Pv-aCO2) may reflect
      the adequacy of blood flow during shock states. We sought to test whether the
      development of Pv-aCO2 during the very early phases of resuscitation is related
      to multi-organ dysfunction and outcomes in a population of septic shock patients
      resuscitated targeting the usual oxygen-derived and hemodynamic parameters.
      METHODS: We conducted a prospective observational study in a 60-bed mixed ICU in
      a University affiliated Hospital. 85 patients with a new septic shock episode
      were included. A Pv-aCO2 value >= 6 mmHg was considered to be high. Patients were
      classified in four predefined groups according to the Pv-aCO2 evolution during
      the first 6 hours of resuscitation: (1) persistently high Pv-aCO2 (high at T0 and
      T6); (2) increasing Pv-aCO2 (normal at T0, high at T6); (3) decreasing Pv-aCO2
      (high at T0, normal at T6); and (4) persistently normal Pv-aCO2 (normal at T0 and
      T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a
      Kaplan Meier curve was constructed to show the survival probabilities at day-28
      using a log-rank test to evaluate differences between groups. A Spearman-Rho was
      used to test the agreement between cardiac output and Pv-aCO2. Finally, we
      calculated the mortality risk ratios at day-28 among patients attaining normal
      oxygen parameters but with a concomitantly increased Pv-aCO2. RESULTS: Patients
      with persistently high and increasing Pv-aCO2 at T6 had significant higher SOFA
      scores at day-3 (p < 0.001) and higher mortality rates at day-28 (log rank test:
      19.21, p < 0.001) compared with patients who evolved with normal Pv-aCO2 at T6.
      Interestingly, a poor agreement between cardiac output and Pv-aCO2 was observed
      (r2 = 0.025, p < 0.01) at different points of resuscitation. Patients who reached
      a central venous saturation (ScvO)2 >= 70% or mixed venous oxygen saturation
      (SvO2) >= 65% but with concomitantly high Pv-aCO2 at different developmental
      points (i.e., T0, T6 and T12) had a significant mortality risk ratio at day-28.
      CONCLUSION: The persistence of high Pv-aCO2 during the early resuscitation of
      septic shock was associated with more severe multi-organ dysfunction and worse
      outcomes at day-28. Although mechanisms conducting to increase Pv-aCO2 during
      septic shock are insufficiently understood, Pv-aCO2 could identify a high risk of
      death in apparently resuscitated patients.

PMID- 24330806
TI  - Will we cure cancer by sequencing thousands of genomes?
AB  - The promise to understand cancer and develop efficacious therapies by sequencing
      thousands of cancers has not occurred. Mutations in specific genes termed
      oncogenes and tumor suppressor genes are extremely heterogeneous amongst the same
      type of cancer as well as between cancers. They provide little selective
      advantage to the cancer and in functional tests have yet to be shown to be
      sufficient for transformation. Here I discuss the karyotyptic theory of cancer
      and ask if it is time for a new approach to understanding and ultimately treating
      cancer. 

PMID- 24330805
TI  - The Older Persons' Transitions in Care (OPTIC) study: pilot testing of the
      transition tracking tool.
AB  - BACKGROUND: OPTIC is a mixed method Partnership for Health System Improvement
      (http://www.cihr-irsc.gc.ca/e/34348.html) study focused on improving care for
      nursing home (NH) residents who are transferred to and from emergency departments
      (EDs) via emergency medical services (EMS). In the pilot study we tested
      feasibility of concurrently collecting individual resident data during
      transitions across settings using the Transition Tracking Tool (T3). METHODS: The
      pilot study tracked 54 residents transferred from NHs to one of two EDs in two
      western Canadian provinces over a three month period. The T3 is an electronic
      data collection tool developed for this study to record data relevant to
      describing and determining success of transitions in care. It comprises 800+ data
      elements including resident characteristics, reasons and precipitating factors
      for transfer, advance directives, family involvement, healthcare services
      provided, disposition decisions, and dates/times and timing. RESULTS: Residents
      were elderly (mean age = 87.1 years) and the majority were female (61.8%).
      Feasibility of collecting data from multiple sources across two research sites
      was established. We identified resources and requirements to access and retrieve
      specific data elements in various settings to manage data collection processes
      and allocate research staff resources. We present preliminary data from NH, EMS,
      and ED settings. CONCLUSIONS: While most research in this area has focused on a
      unidirectional process of patient progression from one care setting to another,
      this study established feasibility of collecting detailed data from beginning to
      end of a transition across multiple settings and in multiple directions.

PMID- 24330807
TI  - Involvement of interleukin-1beta in the autophagic process of microglia:
      relevance to Alzheimer's disease.
AB  - BACKGROUND: Autophagy is a major pathway of protein and organelle degradation in
      the lysosome. Autophagy exists at basal constitutive level and can be induced as
      a defense mechanism under stress conditions. Molecular relationships between
      autophagy and inflammation at the periphery were recently evidenced, highlighting
      a role of autophagy in the regulation of inflammation. Impairment of autophagy
      (with accumulation of autophagic vacuoles) and substantial inflammation are found
      in neurodegenerative diseases such as Alzheimer's Disease (AD). However, the
      links between autophagy and inflammation in AD remain to be determined. METHODS:
      Here, we examined the inflammatory reaction and autophagy in murine tri-cultures
      of neurons, astrocytes, and microglia. Tri-cultures were exposed to various
      inflammatory stresses (lipopolysaccharide (LPS), amyloid peptide (Abeta42) with
      or without cytokines) for 48 hours. Furthermore, the relationships between
      inflammation and autophagy were also analyzed in astrocyte- and microglia
      enriched cultures. Data for multiple variable comparisons were analyzed by a one
      way ANOVA followed by a Newman-keuls' test. RESULTS: Abeta42 induced a low
      inflammation without accumulation of acidic vesicles contrary to moderate or
      severe inflammation induced by LPS or the cytokine cocktail (IL-1beta, TNF-alpha,
      and IL-6) or IL-1beta alone which led to co-localization of p62 and LC3, two
      markers of autophagy, with acidic vesicles stained with Lyso-ID Red dye.
      Moreover, the study reveals a major role of IL-1beta in the induction of
      autophagy in tri-cultures in the presence or absence of Abeta42. However, the
      vulnerability of the autophagic process in purified microglia to IL-1beta was
      prevented by Abeta42. CONCLUSION: These findings show a close relationship
      between inflammation and autophagy, in particular a major role of IL-1beta in the
      induction of the microglial autophagy which could be the case in AD. New
      therapeutic strategies could target inflammasome and autophagy in microglia to
      maintain its role in the amyloid immunosurveillance.

PMID- 24330808
TI  - Changes of peripheral TGF-beta1 depend on monocytes-derived macrophages in
      Huntington disease.
AB  - BACKGROUND: Huntington Disease (HD) is a neurodegenerative disorder resulting
      from the expansion of polyglutamine stretch in the huntingtin protein (Htt).
      Mutant HTT (mHtt) leads to progressive impairment of several molecular pathways
      that have been linked to disease pathogenesis. Defects in the production of a
      number of neurotrophic factors have been described as important determinants
      contributing to the development of HD. We have previously demonstrated that
      production of transforming growth factor-beta1 (TGF-beta1) is also deregulated in
      HD. Peripheral levels of TGF-beta1 were markedly reduced early in the disease and
      returned to normal levels with disease severity. However, the cause and the
      biochemical origin of such abnormalities are still unclear. RESULTS: We report
      here that the abnormal production of peripheral TGF-beta1 depends on the changes
      in the percentage of TGF-beta1-producing macrophages along disease course.
      Variation in the number of TGF-beta1-producing macrophages resulted from
      differential activation state of the same cells, which displayed phenotypic and
      functional heterogeneity throughout the clinical course of HD. We further
      demonstrated that, similar to the periphery, the number of TGF-beta1
      immunoreactive cells in human post-mortem brain with HD, varied with
      neuropathological changes. CONCLUSIONS: Our data indicate that reduced
      bioavailability of TGF-beta1 in the serum of HD subjects is attributable to the
      variation of the number of TGF-beta1-producing macrophages. Macrophages display a
      differential ability to produce TGF-beta1, which reflects diversity in cells
      polarization throughout the disease course. Besides elucidating the biochemical
      origin of TGF-beta1 fluctuations in HD, our study highlights an interesting
      parallelism between periphery and central compartment and underlines the
      potential of TGF-beta1 as a possible indicator suitable for prediction of disease
      onset in HD.

PMID- 24330809
TI  - miR-133b, a muscle-specific microRNA, is a novel prognostic marker that
      participates in the progression of human colorectal cancer via regulation of
      CXCR4 expression.
AB  - BACKGROUND: MicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has
      been reported to be downregulated in human colorectal carcinoma (CRC) when
      compared to adjacent non-tumor tissue. However, its diagnostic value and role in
      CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which
      participates in multiple cell processes such as cell invasion-related signaling
      pathways, was predicted to be a potential target of miR-133b. The aim of this
      study was to investigate the associations and functions of miR-133b and CXCR4 in
      CRC initiation and invasion. METHODS: Mature miR-133b and CXCR4 expression levels
      were detected in 31 tumor samples and their adjacent, non-tumor tissues from
      patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative
      RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to
      validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4
      expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and
      the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were
      evaluated in vitro using the SW-480 and SW-620 CRC cell lines. RESULTS: A
      significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and
      the expression of miR-133b was much lower in metastatic tumors (stage C and D,
      stratified by the Modified Dukes Staging System) than in primary tumors (stage A
      and B). In contrast, CXCR4 protein expression significantly increased in 52.63%
      of CRC samples, and increased CXCR4 expression in CRC was associated with
      advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by
      luciferase reporter assays, and transfection of miR-133b mimics inhibited
      invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells. CONCLUSIONS:
      Our study demonstrated that downregulated miR-133b contributed to increased cell
      invasion and migration in CRC by negatively regulating CXCR4. These findings may
      be significant for the development of therapy target for CRC.

PMID- 24330810
TI  - Efficacy and safety of acupuncture for chronic dizziness: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Dizziness is one of the most challenging symptoms in medicine. No
      medication for dizziness in current use has well-established curative or
      prophylactic value or is suitable for long-term palliative use. Unconventional
      remedies, such as acupuncture, should be considered and scientifically evaluated.
      However, there has been relatively little evidence in randomized controlled
      clinical trials on acupuncture to treat chronic dizziness. The aim of our study
      is to evaluate the efficacy and safety of acupuncture in patients with dizziness.
      METHODS/DESIGN: This trial is a randomized, single-blind, controlled study. A
      total of 80 participants will be randomly assigned to two treatment groups
      receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks.
      The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the
      Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4
      weeks, at a frequency of two sessions per week. The assessment is at baseline
      (before treatment initiation), 4 weeks after the first acupuncture session, and 8
      weeks after the first acupuncture session. DISCUSSION: The results from this
      study will provide clinical evidence on the efficacy and safety of acupuncture in
      patients with chronic dizziness. TRIAL REGISTRATION: International Standard
      Randomized Controlled Trial Number Register: ISRCTN52695239.

PMID- 24330811
TI  - Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor [corrected] antibodies in
      patients with schizophrenia and related psychoses: a systematic review and meta
      analysis.
AB  - BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an
      autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against
      the NR1 subunit of the NMDA glutamate receptor. Approximately 65% of cases
      present with psychiatric symptoms, particularly psychosis. It remains to be
      established whether anti-NMDA receptor antibodies can cause a 'purely' psychotic
      illness without overt neurological symptoms. METHOD: We conducted a systematic
      literature search to establish what proportion of patients with schizophrenia and
      related psychoses have antibodies directed against the NMDA receptor. Studies
      were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia
      spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b)
      serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the
      purpose of the study was to look for the presence of anti-NMDA receptor
      antibodies in patients with a primary psychiatric diagnosis without clinical
      signs of encephalitis. RESULTS: Seven studies were included, comprising 1441
      patients, of whom 115 [7.98%, 95% confidence interval (CI) 6.69-9.50] were anti
      NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94-2.23) patients
      were positive for antibodies of the IgG subclass. Prevalence rates were greater
      in cases than controls only for IgG antibodies; other subclasses are of less
      certain aetiological relevance. There was significant heterogeneity in terms of
      patient characteristics and the antibody assay used. CONCLUSIONS: A minority of
      patients with psychosis are anti-NMDA receptor antibody positive. It remains to
      be established whether this subset of patients differs from antibody-negative
      patients in terms of underlying pathology and response to antipsychotic
      treatment, and whether immunomodulatory treatments are effective in alleviating
      psychotic symptoms in this group.

PMID- 24330812
TI  - Uric acid is a risk factor for ischemic stroke and all-cause mortality in the
      general population: a gender specific analysis from The Tromso Study.
AB  - BACKGROUND: The role of serum uric acid as an independent predictor of
      cardiovascular disease and death is uncertain in the general population.
      Adjustments for additional cardiovascular risk factors have not been consistent.
      We examined the association of serum uric acid with all-cause mortality, ischemic
      stroke and myocardial infarction in a prospective population based study, with
      several traditional and non-traditional risk factors for cardiovascular disease
      included in the model. METHODS: A population-based prospective cohort study was
      performed among 2696 men and 3004 women. Endpoints were all-cause mortality after
      15 years, and fatal or non-fatal myocardial infarction (MI) and ischemic stroke
      after 12 years. RESULTS: 1433 deaths, 659 MIs and 430 ischemic strokes occurred
      during follow-up. Fully adjusted Cox regression analyses showed that per 1 SD (87
      MUmol/L) increase in serum uric acid level, the risk of all-cause mortality
      increased in both genders (hazard ratios, HR men; 1.11, 95% CI 1.02-1.20, women;
      1.16, 1.05-1.29). HRs and 95% CI for stroke were 1.31, 1.14-1.50 in men, 1.13,
      0.94-1.36 in women, and 1.22 (1.09, 1.35) in the overall population. No
      independent associations were observed with MI. CONCLUSION: Serum uric acid was
      associated with all-cause mortality in men and women, even after adjustment for
      blood pressure, estimated GFR, urinary albumin/creatinine ratio, drug intake and
      traditional cardiovascular risk factors. After the same adjustments, serum uric
      acid was associated with 31% increased risk of stroke in men.

PMID- 24330813
TI  - Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and
      phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast
      cancer patients.
AB  - BACKGROUND: Monoclonal antibodies (mAb), such as trastuzumab are a valuable
      addition to breast cancer therapy. Data obtained from neoadjuvant settings
      revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major
      mechanism of action for the mAb trastuzumab. Conflicting results still call into
      question whether disease progression, prolonged treatment or concomitant
      chemotherapy influences ADCC and related immunological phenomena. METHODS: We
      analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis
      (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth
      factor receptor 2 (HER2/neu) positive breast cancer patients receiving
      trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting
      as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients
      (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and
      ADCP activity was correlated with the expression of antibody binding Fc-gamma
      receptor (FcgammaR)I (CD64), FcgammaRII (CD32) and FcgammaRIII (CD16) on CD14+
      (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1)
      on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In
      metastatic patients, markers were correlated with progression-free survival
      (PFS). RESULTS: ADCC activity was significantly down regulated in metastatic,
      adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced
      ADCC activity was inversely correlated with the expression of CD107a on CD56+
      cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were
      similar, regardless of treatment duration or additional chemotherapy. PFS in
      metastatic patients inversely correlated with the number of peripheral Treg
      cells. CONCLUSION: The reduction of ADCC in patients as compared to healthy
      controls calls for adjuvant strategies, such as immune-enhancing agents, to
      improve the activity of trastuzumab. However, efficacy of trastuzumab-specific
      ADCC and ADCP appears not to be affected by treatment duration, disease
      progression or concomitant chemotherapy. This finding supports the application of
      trastuzumab at any stage of the disease.

PMID- 24330814
TI  - A mandatory modification in extracorporeal biventricular assist device (BIVAD)
      implantation: intercostal tunnel application: a case report.
AB  - In this case, our patient was a heart transplant candidate connected to a
      respiratory system. An extracorporeal biventricular assist device (BIVAD) was the
      only option in order to bridge to transplantation. In routine procedures, it is
      recommended that Berlin Heart Excor cannulas be removed through the subfascial
      subcostal tunnel. As the severely dilated right ventricle compressed the apex of
      the left ventricle, which was also dilated to the mid-back zone of the left
      hemithorax, the whole length of the Extracorporeal BIVAD apical cannula had to
      remain within the thorax; however, the cannula was removed from the body by
      creating a tunnel at the 7th intercostal space. In the long-term follow-up, this
      compulsory modification has proven to be safe and effective.

PMID- 24330816
TI  - Characteristics of energy intake under-reporting in French adults.
AB  - Energy intake under-reporting (UR) is a concern in nutritional epidemiological
      studies, as it may distort the relationships between dietary habits and health.
      Although UR is known to be associated with certain characteristics, few studies
      have investigated them in France. Therefore, the goal of the present study was to
      assess the prevalence and characteristics of UR in French adults. UR was defined
      according to Goldberg's classification. A sample of 1567 adults was drawn from
      the nationally representative French dietary survey (Individuelle Nationale des
      Consommations Alimentaires 2 2006-7). Food intake (7 d record), dietary habits,
      socio-economic status, region of residence, sedentary behaviour and weight
      perception variables were assessed. Multivariate logistic regression was used to
      investigate the associations between UR and a number of covariates. The overall
      prevalence of UR was 22.5%, similar in men and women. In both sexes, UR was
      positively associated with overweight and protein intake and inversely associated
      with age. In women, UR was associated with eating lunch in the office, poor
      perception of diet quality and sedentary behaviour and was inversely associated
      with educational level, residence in the Paris region, cereal product intake and
      eating lunch in a friend's or family member's home. In men, UR was positively
      associated with a history of slimming and inversely associated with dairy product
      intake and eating lunch at a staff canteen. In conclusion, UR is prevalent in
      French adults and is associated with several different characteristics. It is
      important to take account of UR when investigating diet-disease associations in
      adults.

PMID- 24330817
TI  - A longitudinal follow-up study of people with Prader-Willi syndrome with
      psychosis and those at increased risk of developing psychosis due to genetic
      subtype.
AB  - BACKGROUND: People with Prader-Willi syndrome (PWS), a genetically defined
      developmental disorder, are at increased risk of developing psychotic illness.
      This is particularly the case for those with a genetic subtype of PWS called
      maternal uniparental disomy (mUPD), where rates of psychosis are more than 60% by
      early adult life. Little is known about the long-term course of their disorder.
      METHOD: Individuals who had had episodes of psychosis or were at increased risk
      of developing psychosis due to their genetic subtype and had taken part in a
      previous study were contacted. Ten people were untraceable or deceased, leaving a
      total of 38 potential participants. Of these, 28 agreed to take part in a follow
      up interview or complete a questionnaire about their mental health and
      medication. This represented 20/35 (57.1%) people from the original study who had
      had psychosis and 8/13 (61.5%) people who were at risk due to their genetic
      subtype. They were thought to be representative of those groups as a whole based
      on IQ and number of episodes of psychosis. RESULTS: Two individuals had had
      recurrent episodes of psychosis while all others remained well. There were no new
      onset cases of psychosis in those at risk. Individuals with PWS remained on high
      levels of psychiatric medication throughout the follow-up period. CONCLUSIONS:
      Recurrent episodes of psychosis may be rare in people with PWS once stability has
      been achieved in the management of their illness. We speculate that this may be
      due to the protective influence of medication.

PMID- 24330815
TI  - Hemodynamic variables and progression of acute kidney injury in critically ill
      patients with severe sepsis: data from the prospective observational FINNAKI
      study.
AB  - INTRODUCTION: Knowledge of the association of hemodynamics with progression of
      septic acute kidney injury (AKI) is limited. However, some recent data suggest
      that mean arterial pressure (MAP) exceeding current guidelines (60-65 mmHg) may
      be needed to prevent AKI. We hypothesized that higher MAP during the first 24
      hours in the intensive care unit (ICU), would be associated with a lower risk of
      progression of AKI in patients with severe sepsis. METHODS: We identified 423
      patients with severe sepsis and electronically recorded continuous hemodynamic
      data in the prospective observational FINNAKI study. The primary endpoint was
      progression of AKI within the first 5 days of ICU admission defined as new onset
      or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO)
      criteria. We evaluated the association of hemodynamic variables with this
      endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed
      the ability of time-adjusted MAP to predict progression of AKI by receiver
      operating characteristic (ROC) analysis. RESULTS: Of 423 patients, 153 (36.2%)
      had progression of AKI. Patients with progression of AKI had significantly lower
      time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6
      mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP
      best predicted the progression of AKI. Chronic kidney disease, higher lactate,
      higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg
      were independent predictors of progression of AKI. CONCLUSIONS: The findings of
      this large prospective multicenter observational study suggest that hypotensive
      episodes (MAP under 73 mmHg) are associated with progression of AKI in critically
      ill patients with severe sepsis.

PMID- 24330818
TI  - Chronic conditions and household preparedness for public health emergencies:
      Behavioral Risk Factor Surveillance System, 2006-2010.
AB  - INTRODUCTION: Individuals with chronic conditions often experience exacerbation
      of those conditions and have specialized medical needs after a disaster. Less is
      known about the level of disaster preparedness of this particular population and
      the extent to which being prepared might have an impact on the risk of disease
      exacerbation. The purpose of this study was to examine the association between
      self-reported asthma, cardiovascular disease, and diabetes and levels of
      household disaster preparedness. METHODS: Data were analyzed from 14 US states
      participating in the 2006-2010 Behavioral Risk Factor Surveillance System
      (BRFSS), a large state-based telephone survey. Chi-square statistics and adjusted
      prevalence ratios were calculated. RESULTS: After adjusting for sociodemographic
      characteristics, as compared to those without each condition, persons with
      cardiovascular disease (aPR = 1.09; 95% CI, 1.01-1.17) and diabetes (aPR = 1.13;
      95% CI, 1.05-1.22) were slightly more likely to have an evacuation plan and
      individuals with diabetes (aPR = 1.04; 95% CI, 1.02-1.05) and asthma (aPR = 1.02;
      95% CI, 1.01-1.04) were slightly more likely to have a 3-day supply of
      prescription medication. There were no statistically significant differences in
      the prevalence for all other preparedness measures (3-day supply of food and
      water, working radio and flashlight, willingness to leave during a mandatory
      evacuation) between those with and those without each chronic condition.
      CONCLUSION: Despite the increased morbidity and mortality associated with chronic
      conditions, persons with diabetes, cardiovascular disease, and asthma were
      generally not more prepared for natural or man-made disasters than those without
      each chronic condition.

PMID- 24330819
TI  - Involvement of the N-methyl-D-aspartate receptor GluN2D subunit in phencyclidine
      induced motor impairment, gene expression, and increased Fos immunoreactivity.
AB  - BACKGROUND: Noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists evoke
      a behavioral and neurobiological syndrome in experimental animals. We previously
      reported that phencyclidine (PCP), an NMDA receptor antagonist, increased
      locomotor activity in wildtype (WT) mice but not GluN2D subunit knockout mice.
      Thus, the aim of the present study was to determine whether the GluN2D subunit is
      involved in PCP-induced motor impairment. RESULTS: PCP or UBP141 (a GluN2D
      antagonist) induced potent motor impairment in WT mice but not GluN2D KO mice. By
      contrast, CIQ, a GluN2C/2D potentiator, induced severe motor impairment in GluN2D
      KO mice but not WT mice, suggesting that the GluN2D subunit plays an essential
      role in the effects of PCP and UBP141, and an appropriate balance between GluN2C
      and GluN2D subunits might be needed for appropriate motor performance. The level
      of the GluN2D subunit in the mature mouse brain is very low and restricted.
      GluN2D subunits exist in brainstem structures, the globus pallidus, thalamus, and
      subthalamic nucleus. We found that the expression of the c-fos gene increased the
      most among PCP-dependent differentially expressed genes between WT and GluN2D KO
      mice, and the number of Fos-positive cells increased after PCP administration in
      the basal ganglia motor circuit in WT mice but not GluN2D KO mice. CONCLUSION:
      These results suggest that the GluN2D subunit within the motor circuitry is a key
      subunit for PCP-induced motor impairment, which requires an intricate balance
      between GluN2C- and GluN2D-mediated excitatory outputs.

PMID- 24330820
TI  - Physicians' perceptions of quality of care, professional autonomy, and job
      satisfaction in Canada, Norway, and the United States.
AB  - BACKGROUND: We lack national and cross-national studies of physicians'
      perceptions of quality of patient care, professional autonomy, and job
      satisfaction to inform clinicians and policymakers. This study aims to compare
      such perceptions in Canada, the United States (U.S.), and Norway. METHODS: We
      analyzed data from large, nationwide, representative samples of physicians in
      Canada (n = 3,213), the U.S. (n = 6,628), and Norway (n = 657), examining
      demographics, job satisfaction, and professional autonomy. RESULTS: Among U.S.
      physicians, 79% strongly agreed/agreed they could provide high quality patient
      care vs. only 46% of Canadian and 59% of Norwegian physicians. U.S. physicians
      also perceived more clinical autonomy and time with their patients, with
      differences remaining significant even after controlling for age, gender, and
      clinical hours. Women reported less adequate time, clinical freedom, and ability
      to provide high-quality care. Country differences were the strongest predictors
      for the professional autonomy variables. In all three countries, physicians'
      perceptions of quality of care, clinical freedom, and time with patients
      influenced their overall job satisfaction. Fewer U.S. physicians reported their
      overall job satisfaction to be at-least-somewhat satisfied than did Norwegian and
      Canadian physicians. CONCLUSIONS: U.S. physicians perceived higher quality of
      patient care and greater professional autonomy, but somewhat lower job
      satisfaction than their colleagues in Norway and Canada. Differences in health
      care system financing and delivery might help explain this difference; Canada and
      Norway have more publicly-financed, not-for-profit health care delivery systems,
      vs. a more-privately-financed and profit-driven system in the U.S. None of these
      three highly-resourced countries, however, seem to have achieved an ideal health
      care system from the perspective of their physicians.

PMID- 24330821
TI  - Mitochondrial permeability transition pore induces mitochondria injury in
      Huntington disease.
AB  - BACKGROUND: Mitochondrial impairment has been implicated in the pathogenesis of
      Huntington's disease (HD). However, how mutant huntingtin impairs mitochondrial
      function and thus contributes to HD has not been fully elucidated. In this study,
      we used striatal cells expressing wild type (STHdhQ7/Q7) or mutant
      (STHdhQ111/Q111) huntingtin protein, and cortical neurons expressing the exon 1
      of the huntingtin protein with physiological or pathological polyglutamine
      domains, to examine the interrelationship among specific mitochondrial functions.
      RESULTS: Depolarization induced by KCl resulted in similar changes in calcium
      levels without compromising mitochondrial function, both in wild type and mutant
      cells. However, treatment of mutant cells with thapsigargin (a SERCA antagonist
      that raises cytosolic calcium levels), resulted in a pronounced decrease in
      mitochondrial calcium uptake, increased production of reactive oxygen species
      (ROS), mitochondrial depolarization and fragmentation, and cell viability loss.
      The mitochondrial dysfunction in mutant cells was also observed in cortical
      neurons expressing exon 1 of the huntingtin protein with 104 Gln residues (Q104
      GFP) when they were exposed to calcium stress. In addition, calcium overload
      induced opening of the mitochondrial permeability transition pore (mPTP) in
      mutant striatal cells. The mitochondrial impairment observed in mutant cells and
      cortical neurons expressing Q104-GFP was prevented by pre-treatment with
      cyclosporine A (CsA) but not by FK506 (an inhibitor of calcineurin), indicating a
      potential role for mPTP opening in the mitochondrial dysfunction induced by
      calcium stress in mutant huntingtin cells. CONCLUSIONS: Expression of mutant
      huntingtin alters mitochondrial and cell viability through mPTP opening in
      striatal cells and cortical neurons.

PMID- 24330822
TI  - The long-term ingestion of a diet high in extra virgin olive oil produces obesity
      and insulin resistance but protects endothelial function in rats: a preliminary
      study.
AB  - BACKGROUND: It has been hypothesized that fatty acids derived from a diet high in
      saturated fat may negatively affect endothelial function more significantly than
      a diet high in unsaturated fat; nevertheless, the effects of the long-term
      ingestion of monounsaturated fatty acids on endothelial function have been poorly
      studied. METHODS: To examine the chronic effects of monounsaturated (e.g., extra
      virgin olive oil (EVOO)) or saturated (e.g., margarine (M)) fatty acid-rich diets
      on the development of insulin resistance and endothelial dysfunction in rats,
      three groups of rats were fed control, high-EVOO or high-M diets for 20 weeks.
      Body weight, energy consumption, insulin resistance, lipid peroxidation and in
      vitro vascular reactivity with and without metformin were assessed during the
      study period. RESULTS: Both high-fat diets produced obesity and insulin
      resistance. EVOO-fed rats showed smaller increases in total cholesterol and
      arterial lipid peroxidation when compared with M-fed rats. Vascular reactivity to
      phenylephrine and sodium nitroprusside was not modified, but the vasodilating
      effect of carbachol was especially reduced in the M-fed rats compared with the
      EVOO-fed or control groups. Metformin addition to the incubation media decreased
      the vascular response to phenylephrine; decrease that was lower in rats fed with
      both high fat diets, and increased the carbachol and nitroprusside effects, but
      the metformin-enhanced response to carbachol was lower in the M group.
      CONCLUSIONS: Our results suggest that feeding rats with high quantities of EVOO,
      despite producing obesity and insulin resistance, produces low levels of
      circulating cholesterol and arterial lipoperoxidation compared to M fed rats and
      shows a preserved endothelial response to carbachol, effect that is significantly
      enhanced by metformin only in rats fed with control and EVOO diets.

PMID- 24330823
TI  - The therapeutic efficacy of I131-PSCA-mAb in orthotopic mouse models of prostate
      cancer.
AB  - BACKGROUND: Prostate stem cell antigen (PSCA) is upregulated in prostate cancer
      tissues. Here we aimed to study the therapeutic efficacy of a monoclonal antibody
      of PSCA-labeled I131 (I131-PSCA-mAb) in orthotopic mouse models of prostate
      cancer. METHODS: The proliferation, apoptosis and invasion abilities of PC-3 and
      LNCaP cells treated with I131-PSCA-mAb were measured by methyl thiazolyl
      tetrazolium assay, flow cytometry and transwell culture, respectively. The human
      prostate cancer models were established by orthotopic implantation of PC-3 and
      LNCaP cells in nude mice. I131-PSCA-mAb distribution and tumor cell apoptosis in
      the tumor-bearing nude mice were measured. RESULTS: The inhibitory and apoptosis
      rates of PC-3 and LNCaP cells treated with I131-PSCA-mAb reached a maximum of
      84%, 80% and 50%, 46%, respectively, which were obviously higher than in the
      cells treated with I131-IgG or PSCA-mAb. The invaded number of PC-3 and LNCaP
      cells treated with I131-PSCA-mAbe was significantly reduced (P < 0.01) compared
      with the control group. The ratios of I131-PSCA-mAb in tumor to intramuscular
      I131-PSCA-mAb (T/NT) in tumor-bearing nude mice were increased with time and
      reached the highest level after 8 h. T/NT stayed above 3.0 after 12 h, and the
      tumor could still be developed after 24 h. The number of apoptotic cells in tumor
      tissue of nude mice treated with I131-PSCA-mAb was larger than that in the
      control group. CONCLUSION: I131-PSCA-mAb has the potential to become a new
      targeted therapy drug for the treatment of prostate cancer.

PMID- 24330825
TI  - 3D ultrasonography to evaluate fetal urinary production rates in twin gestation:
      construction of a normal value curve.
AB  - OBJECTIVE: The aim of this study was to assess fetal urinary production rates
      (FUPR) in twin gestations using 3D ultrasonography with VOCAL(r) (virtual organ
      computer-aided analysis) and to develop a curve of normal values for the target
      population. METHODS: A cross-sectional study was performed in 30 normal twin
      pregnancies with gestational ages ranging from 20 to 34 weeks. FUPR was measured
      using a three-dimensional ultrasound (3D US) virtual organ computer-aided
      analysis (VOCAL) system. FUPR (ml/hour) was calculated during the filling phase
      using the equation UPR = (VFB(2) - VFB(1))/time. The values for UPR were plotted
      as a function of fetal biometry (biparietal diameter) to generate a nomogram.
      RESULTS: A total of 41 normal twin fetuses with gestational ages between 20 and
      34 weeks were investigated. Eleven were excluded because of inadequate bladder
      contour image quality and/or the observation of micturition in one or both
      fetuses. Linear regression analysis of FUPR as a function of biparietal diameter
      (BPD) shows the normal range for UPR by fetal biometry and is expressed by the
      following equation: Ln(UPR) = -5.0121 + 0.0548 BPD (R(2) 0.3386, p value <.001).
      There was no statistically significant difference when the UPR was stratified by
      chorionicity. CONCLUSIONS: The use of biometric parameters to predict fetal FUPR
      seems to be useful. In twin pregnancies, BPD is the variable that is most closely
      related to FUPR. For each 1 mm increase in BPD, there is a 5% increase in FUPR.
      Chorionicity did not affect FUPR.

PMID- 24330824
TI  - Correlation of WWOX, RUNX2 and VEGFA protein expression in human osteosarcoma.
AB  - BACKGROUND: To investigate associations between WW domain-containing
      oxidoreductase (WWOX), runt-related transcription factor 2 (RUNX2) and vascular
      endothelial growth factor alpha (VEGFA) in human osteosarcoma (OS). METHODS: Copy
      number aberrations of WWOX, RUNX2and VEGFA genes were detected by microarray
      comparative genomic hybridization (aCGH) in 10 fresh OS tissue samples. VEGFA
      gene alterations were also investigated and validated by fluorescence in situ
      hybridization (FISH) in 54 formalin-fixed and paraffin-embedded (FFPE) OS
      samples. Protein expression of WWOX, RUNX2 and VEGFA were examined in 54 FFPE OS
      samples by immunohistochemistry (IHC). RESULTS: Analysis of previously published
      OS aCGH data (GSE9654) and aCGH data from this study (GSE19180) identified
      significant deletion of WWOX in 30% (6/20) of OS samples, whilst significant
      increase in both RUNX2 and VEGFA gene copy numbers were detected in 55% (11/20)
      and 60% (12/20) of OS samples, respectively. FISH demonstrated increased VEGFA
      gene copy number in 65.9% (31/47) of evaluable samples, in either focal or large
      fragment forms. Compared with positive expression of WWOX in 38.9% of the OS
      samples, positive expression of RUNX2 and VEGFA protein was found in 48.1 and
      75.9% of samples. Although there was no significant association between gene copy
      number aberration and protein expression for WWOX and RUNX2, significant positive
      correlation between increased VEGFA gene copy number and VEGFA protein expression
      was observed. Although there was no significant reverse association between WWOX
      and RUNX2 expression, a significantly positive relationship was observed between
      RUNX2 and VEGFA protein expression. CONCLUSIONS: Our data show increased RUNX2
      and VEGFA gene copy numbers and elevation of their respective proteins in human
      OS. Positive correlation of RUNX2 and VEGFA suggests that both increased VEGFA
      gene copy number and RUNX2 overexpression facilitate increased expression of
      VEGFA.

PMID- 24330826
TI  - How to switch to agomelatine after an unsuccessful try with paroxetine or
      venlafaxine.
AB  - OBJECTIVE/INTRODUCTION: The present trial informs clinicians about switching
      conditions with the antidepressant agomelatine after the failure of a treatment
      with either paroxetine or venlafaxine. METHODS: The total number of
      discontinuation-emergent symptoms, according to the Discontinuation-Emergent
      Signs and Symptoms checklist, was compared in double-blind conditions after 3
      switching options: immediate substitution or initiation of agomelatine (25 mg/day
      p.o.) with either a short- or long-tapering of the previous drug. Secondary
      objectives included tolerability and safety assessments and the early clinical
      benefit after the switch. RESULTS: For all switching options, a withdrawal
      syndrome was observed 1 week after cessation of the selective serotonin reuptake
      inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) treatment.
      Psychic symptoms were the most frequently reported, and somatic symptoms were
      comparatively few. Early discontinuation symptoms after cessation of SSRI/SNRI
      treatment did not prejudice the antidepressant benefits of agomelatine over 8
      weeks. CONCLUSIONS: Both abrupt and start-taper switching with agomelatine are
      options in everyday practice for those patients who have not responded to either
      paroxetine or venlafaxine. However, regardless of the switching strategy, the
      present double-blind study shows that early discontinuation symptoms that arise
      upon cessation of SSRI/SNRI can alter the patients' perception of the clinical
      benefit of the new antidepressant. Both practitioners and patients must be warned
      about these early discontinuation symptoms to prevent the symptoms from being
      confounded with a lack of therapeutic benefit of the new treatment.

PMID- 24330827
TI  - Inflammasome induction in Rasmussen's encephalitis: cortical and associated white
      matter pathogenesis.
AB  - BACKGROUND: Rasmussen's encephalitis (RE) is an inflammatory encephalopathy of
      unknown cause defined by seizures with progressive neurological disabilities.
      Herein, the pathogenesis of RE was investigated focusing on inflammasome
      activation in the brain. METHODS: Patients with RE at the University of Alberta,
      Edmonton, AB, Canada, were identified and analyzed by neuroimaging,
      neuropsychological, molecular, and pathological tools. Primary human microglia,
      astrocytes, and neurons were examined using RT-PCR, enzyme-linked immunosorbent
      assay (ELISA), and western blotting. RESULTS: Four patients with RE were
      identified at the University of Alberta. Magnetic resonance imaging (MRI)
      disclosed increased signal intensities in cerebral white matter adjacent to
      cortical lesions of RE patients, accompanied by a decline in neurocognitive
      processing speed (P <0.05). CD3epsilon, HLA-DRA, and TNFalpha together with
      several inflammasome-associated genes (IL-1beta, IL-18, NLRP1, NLRP3, and CASP1)
      showed increased transcript levels in RE brains compared to non-RE controls (n =
      6; P <0.05). Cultured human microglia displayed expression of inflammasome
      associated genes and responded to inflammasome activators by releasing IL-1beta,
      which was inhibited by the caspase inhibitor, zVAD-fmk. Major histocompatibility
      complex (MHC) class II, IL-1beta, caspase-1, and alanine/serine/cysteine (ASC)
      immunoreactivity were increased in RE brain tissues, especially in white matter
      myeloid cells, in conjunction with mononuclear cell infiltration and gliosis.
      Neuroinflammation in RE brains was present in both white matter and adjacent
      cortex with associated induction of inflammasome components, which was correlated
      with neuroimaging and neuropsychological deficits. CONCLUSION: Inflammasome
      activation likely contributes to the disease process underlying RE and offers a
      mechanistic target for future therapeutic interventions.

PMID- 24330830
TI  - The neuroscience of free will: implications for psychiatry.
AB  - Belief in free will has been a mainstay in philosophy throughout history,
      grounded in large part in our intuitive sense that we consciously control our
      actions and could have done otherwise. However, psychology and psychiatry have
      long sought to uncover mechanistic explanations for human behavior that challenge
      the notion of free will. In recent years, neuroscientific discoveries have
      produced a model of volitional behavior that is at odds with the notion of contra
      causal free will and our sense of conscious agency. Volitional behavior instead
      appears to have antecedents in unconscious brain activity that is localizable to
      specific neuroanatomical structures. Updating notions of free will in favor of a
      continuous model of volitional self-control provides a useful paradigm to
      conceptualize and study some forms of psychopathology such as addiction and
      impulse control disorders. Similarly, thinking of specific symptoms of
      schizophrenia as disorders of agency may help to elucidate mechanisms of
      psychosis. Beyond clinical understanding and etiological research, a
      neuroscientific model of volitional behavior has the potential to modernize
      forensic notions of responsibility and criminal punishment in order to inform
      public policy. Ultimately, moving away from the language of free will towards the
      language of volitional control may result in an enhanced understanding of the
      very nature of ourselves. 

PMID- 24330829
TI  - In triple negative breast tumor cells, PLC-beta2 promotes the conversion of
      CD133high to CD133low phenotype and reduces the CD133-related invasiveness.
AB  - BACKGROUND: Beyond its possible correlation with stemness of tumor cells,
      CD133/prominin1 is considered an important marker in breast cancer, since it
      correlates with tumor size, metastasis and clinical stage of triple-negative
      breast cancers (TNBC), to date the highest risk breast neoplasia. METHODS: To
      study the correlation between the levels of CD133 expression and the biology of
      breast-derived cells, CD133low and CD133high cell subpopulations isolated from
      triple negative MDA-MB-231 cells were compared in terms of malignant properties
      and protein expression. RESULTS: High expression of CD133 characterizes cells
      with larger adhesion area, lower proliferation rate and reduced migration speed,
      indicative of a less undifferentiated phenotype. Conversely, when compared with
      CD133low cells, CD133high cells show higher invasive capability and increased
      expression of proteins involved in metastasis and drug-resistance of breast
      tumors. Among the signalling proteins examined, PLC-beta2 expression inversely
      correlates with the levels of CD133 and has a role in inducing the CD133high
      cells to CD133low cells conversion, suggesting that, in TNBC cells, the de
      regulation of this PLC isoform is responsible of the switch from an early to a
      mature tumoral phenotype also by reducing the expression of CD133. CONCLUSIONS:
      Since CD133 plays a role in determining the invasiveness of CD133high cells, it
      may constitute an attractive target to reduce the metastatic potential of TNBC.
      In addition, our data showing that the forced up-regulation of PLC-beta2
      counteracts the invasiveness of CD133-positive MDA-MB-231 cells might contribute
      to identify unexplored key steps responsible for the TNBC high malignancy, to be
      considered for potential therapeutic strategies.

PMID- 24330828
TI  - Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including
      regulatory variants near CDKN2A/B.
AB  - BACKGROUND: Canine osteosarcoma is clinically nearly identical to the human
      disease, but is common and highly heritable, making genetic dissection feasible.
      RESULTS: Through genome-wide association analyses in three breeds (greyhounds,
      Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining
      55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting
      the strongest association, located 150 kilobases upstream of the genes CDKN2A/B,
      is also the most rearranged locus in canine osteosarcoma tumors. The top germline
      candidate variant is found at a >90% frequency in Rottweilers and Irish
      wolfhounds, and alters an evolutionarily constrained element that we show has
      strong enhancer activity in human osteosarcoma cells. In all three breeds,
      osteosarcoma-associated loci and regions of reduced heterozygosity are enriched
      for genes in pathways connected to bone differentiation and growth. Several
      pathways, including one of genes regulated by miR124, are also enriched for
      somatic copy-number changes in tumors. CONCLUSIONS: Mapping a complex cancer in
      multiple dog breeds reveals a polygenic spectrum of germline risk factors
      pointing to specific pathways as drivers of disease.

PMID- 24330832
TI  - Lanthanum carbonate prevents accelerated medial calcification in uremic rats:
      role of osteoclast-like activity.
AB  - BACKGROUND: Arterial medial calcification (AMC) is frequent prevalence in
      patients with end stage renal disease. Evidence about hyperphosphatemia induced
      anabolic crosstalk between osteoblast and osteoclast in AMC of uremia is rare.
      Lanthanum carbonate as an orally administered phosphate-binding agent to reduce
      phosphate load and ameliorate AMC, but direct evidence is missing. METHODS:
      Detailed time-course studies were conducted of Sprague-Dawley rats fed with
      adenine and high phosphate diet to imitate the onset and progression of AMC of
      uremia. Calcification in great arteries was evaluated by VonKossa's and Masson's
      trichrome staining. Osteoblast (Runx2, Osteocalcin) and osteoclast (RANKL,
      Cathepsin K, TRAP) related genes were analyzed by Immunohistochemistry and qRT
      PCR. Serum PTH, RANKL and OPG levels were detected by ELISA kit. RESULTS: Serum
      phosphate was markedly increased in CRF group (6.94 +/- 0.97 mmol/L) and 2%La
      group (5.12 +/- 0.84 mmol/L) at week 4, while the latter group diminished
      significantly (2.92 +/- 0.73 mmol/L vs CRF Group 3.48 +/- 0.69, p < 0.01) at week
      10. The rats that did not receive 2%La treatment had extensive von kossa staining
      for medial calcification in CRF group. In contrast, the rats in 2%La group just
      exhibit mild medial calcification. Inhibitory effect on progression of AMC was
      reflected by down regulated osteogenic genes and altered osteoclast-like genes.
      RANKL/OPG ratio in local calcification area was declined in 2%La group (vs CRF
      group, p <0.01), whereas marginal difference in serum among the three groups. In
      contrast to the robust expression of cathepsinK in calcified area, TRAP
      expression was not found. CONCLUSIONS: Abnormal phosphate homeostasis, induction
      of osteogenic conversion and osteoclast suppression were contributed to the
      current mechanisms of uremia associated arterial medial calcification based on
      our studies. Beneficial effects of Lanthanum carbonate could be mainly due to the
      decreased phosphate retention and cross-talk between osteoblast and osteoclast
      like cell, both of which can be the therapeutic target for uremia associated with
      AMC.

PMID- 24330833
TI  - Murine esBAF chromatin remodeling complex subunits BAF250a and Brg1 are necessary
      to maintain and reprogram pluripotency-specific replication timing of select
      replication domains.
AB  - BACKGROUND: Cellular differentiation and reprogramming are accompanied by changes
      in replication timing and 3D organization of large-scale (400 to 800 Kb)
      chromosomal domains ('replication domains'), but few gene products have been
      identified whose disruption affects these properties. RESULTS: Here we show that
      deletion of esBAF chromatin-remodeling complex components BAF250a and Brg1, but
      not BAF53a, disrupts replication timing at specific replication domains. Also,
      BAF250a-deficient fibroblasts reprogrammed to a pluripotency-like state failed to
      reprogram replication timing in many of these same domains. About half of the
      replication domains affected by Brg1 loss were also affected by BAF250a loss, but
      a much larger set of domains was affected by BAF250a loss. esBAF binding in the
      affected replication domains was dependent upon BAF250a but, most affected
      domains did not contain genes whose transcription was affected by loss of esBAF.
      CONCLUSIONS: Loss of specific esBAF complex subunits alters replication timing of
      select replication domains in pluripotent cells.

PMID- 24330834
TI  - Akt inhibitors: mechanism of action and implications for anticancer therapeutics.
AB  - Akt, better known as protein kinase B (PKB), is a serine/threonine-specific
      protein kinase which acts as mediator via PI3K/Akt pathway in many biological
      processes like glucose metabolism, apoptosis, cell differentiation and
      transcription. Akt1 gene amplification has been implicated in gastric carcinoma
      while Akt2 amplification has been linked with ovarian, pancreas, breast and
      stomach tumors. The use of Akt inhibitors as monotherapy or in combination with
      other anticancer drugs could be useful for combating drug resistance and
      improving response. Thus, comprehensive understanding of Akt and its linked
      signaling pathways (PI3K, PKB, mTOR etc.) is necessary to lead to newer drug
      development and use. 

PMID- 24330835
TI  - Occurrence of potentially pathogenic nontuberculous mycobacteria in Mexican
      household potable water: a pilot study.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) are environmental opportunistic
      pathogens found in natural and human-engineered waters, including drinking water
      distribution systems and household plumbing. This pilot study examined the
      frequency of occurrence of NTM in household potable water samples in Mexico City.
      Potable water samples were collected from the "main house faucet" and kitchen
      faucet. The presence of aerobic-mesophilic bacteria (AMB), total coliforms (TC),
      fecal coliforms (FC) and NTM species were determined. Mycobacteria species were
      identified by PCR restriction enzyme pattern analysis (PRA) of the 65-kDa heat
      shock protein gene (hsp65) and sequencing of the hypervariable region 2 (V2) of
      the 16S rRNA gene and of the rpoB gene. RESULTS: AMB (<100 CFU/ml) were present
      in 118 out of 120 samples; only two samples were outside guidelines ranges (>100
      CFU/ml). TC and FC were detected in four and one samples, respectively. NTM
      species were recovered from 16% samples (19/120) and included M. mucogenicum
      (nine), M. porcinum (three), M. avium (three), M. gordonae (one), M. cosmeticum
      (one), M. fortuitum (one), and Mycobacterium sp (one). All household water
      samples that contained NTM complied with the standards required to grade the
      water as "good quality" potable water. CONCLUSION: Household potable water may be
      a potential source of NTM infection in Mexico City.

PMID- 24330831
TI  - Influence of parental socio-economic status on diet quality of European
      adolescents: results from the HELENA study.
AB  - Diet quality is influenced by socio-economic and geographical factors. The
      present study sought to assess whether adolescents' diet quality is affected by
      their parents' socio-economic status and whether the relationship between these
      factors is similar in northern and southern Europe. Data collected in the Healthy
      Lifestyle in Europe by Nutrition in Adolescence (HELENA) study in eight European
      countries were analysed. Dietary intake data were recorded via repeated 24 h
      recalls (using specifically developed HELENA Dietary Intake Assessment Tool
      software) and converted into an adolescent-specific Diet Quality Index (DQI-AM).
      Socio-economic status was estimated through parental educational level (Par-Educ
      Lev) and parental occupation level (Par-Occ-Lev) as reported by the adolescents
      in a specific questionnaire. The DQI-AM data were then analysed as a function of
      Par-Educ-Lev and Par-Occ-Lev in northern European countries (Austria, Belgium,
      France, Germany and Sweden) and southern European countries (Greece, Italy and
      Spain). We studied a total of 1768 adolescents (age 14.7 (SD 1.3) years;
      percentage of girls: 52.8%; 1135 and 633 subjects from northern and southern
      Europe, respectively). On average, the DQI-AM score was higher in southern Europe
      than in northern Europe (69.1 (SD 0.1) v. 60.4 (SD 2.8), respectively; P < 0.001;
      Delta = 12.6%). The DQI was positively correlated with both paternal and maternal
      Par-Educ-Lev. However, this association was more pronounced in northern Europe
      than in southern Europe (P interaction = 0.004 for the mother and 0.06 for the
      father). The DQI was also positively correlated with Par-Occ-Lev (all P trends <
      0.01), but this correlation was independent of the geographical area (P
      interaction = 0.51 for the mother and 0.50 for the father). In conclusion, Par
      Educ-Lev and Par-Occ-Lev are associated with diet quality in adolescents in
      Europe. However, this association differs between northern Europe and southern
      Europe.

PMID- 24330836
TI  - Crosstalk between circulating peroxisome proliferator-activated receptor gamma,
      adipokines and metabolic syndrome in obese subjects.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) has
      direct and indirect function in adipokines production process. We aimed to assess
      the possible influence of circulating PPARgamma on relative risk of metabolic
      syndrome and also examine the association between circulating PPARgamma and
      adipokines levels among obese subjects. METHODS: A total of 96 obese subjects
      (body mass index (BMI) >=30) were included in the current cross-sectional study.
      We assessed the body composition with the use of Body Composition Analyzer BC
      418MA - Tanita. The MetS (metabolic syndrome) was defined based on the National
      Cholesterol Education Program Adult Treatment Panel III. All baseline blood
      samples were obtained following an overnight fasting. Serum concentrations of
      adipokines including Retinol binding protein 4 (RBP4), omentin-1, vaspin,
      progranulin, nesfatin-1 and circulating PPARgamma was measured with the use of an
      enzyme-linked immunosorbent assay method. Statistical analyses were performed
      using software package used for statistical analysis (SPSS). RESULTS: We found
      main association between circulating PPARgamma and body composition in obese
      population. The risk of metabolic syndrome in subjects with higher concentration
      of PPARgamma was 1.9 fold in compared with lower concentration of PPARgamma after
      adjustment for age, sex and BMI. There was significant association between
      PPARgamma and adipokines, specially nesfatin-1 and progranulin. Defined
      adipokines pattern among participants demonstrated the markedly higher
      concentration of vaspin, RBP4 and nesfatin-1 in participants with MetS compared
      to non-MetS subjects. CONCLUSIONS: It appears all of studied adipokines might
      have association with PPARgamma level and might simultaneously be involve in some
      common pathway to make susceptible obese subjects for MetS.

PMID- 24330837
TI  - CD8+ T cells from HLA-B*57 elite suppressors effectively suppress replication of
      HIV-1 escape mutants.
AB  - BACKGROUND: Elite Controllers or Suppressors (ES) are HIV-1 positive individuals
      who maintain plasma viral loads below the limit of detection of standard clinical
      assays without antiretroviral therapy. Multiple lines of evidence suggest that
      the control of viral replication in these patients is due to a strong and
      specific cytotoxic T lymphocyte (CTL) response. The ability of CD8+ T cells to
      control HIV-1 replication is believed to be impaired by the development of escape
      mutations. Surprisingly, viruses amplified from the plasma of ES have been shown
      to contain multiple escape mutations, and it is not clear how immunologic control
      is maintained in the face of virologic escape. RESULTS: We investigated the
      effect of escape mutations within HLA*B-57-restricted Gag epitopes on the CD8+ T
      cell mediated suppression of HIV-1 replication. Using site directed mutagenesis,
      we constructed six NL4-3 based viruses with canonical escape mutations in one to
      three HLA*B-57-restricted Gag epitopes. Interestingly, similar levels of CTL
      mediated suppression of replication in autologous primary CD4+ T cells were
      observed for all of the escape mutants. Intracellular cytokine staining was
      performed in order to determine the mechanisms involved in the suppression of the
      escape variants. While low baseline CD8+ T cells responses to wild type and
      escape variant peptides were seen, stimulation of PBMC with either wild type or
      escape variant peptides resulted in increased IFN-gamma and perforin expression.
      CONCLUSIONS: These data presented demonstrate that CD8+ T cells from ES are
      capable of suppressing replication of virus harboring escape mutations in HLA
      B*57-restricted Gag epitopes. Additionally, our data suggest that ES CD8+ T cells
      are capable of generating effective de novo responses to escape mutants.

PMID- 24330838
TI  - Establishing an osteosarcoma associated protein-protein interaction network to
      explore the pathogenesis of osteosarcoma.
AB  - BACKGROUND: The aim of this study was to establish an osteosarcoma (OS)
      associated protein-protein interaction network and explore the pathogenesis of
      osteosarcoma. METHODS: The gene expression profile GSE9508 was downloaded from
      the Gene Expression Omnibus database, including five samples of non-malignant
      bone (the control), seven samples for non-metastatic patients (six of which were
      analyzed in duplicate), and 11 samples for metastatic patients (10 of which were
      analyzed in duplicate). Differentially expressed genes (DEGs) between
      osteosarcoma and control samples were identified by packages in R with the
      threshold of |logFC (fold change)| > 1 and false discovery rate < 0.05. Osprey
      software was used to construct the interaction network of DEGs, and genes at
      protein-protein interaction (PPI) nodes with high degrees were identified. The
      Database for Annotation, Visualization and Integrated Discovery and WebGestalt
      software were then used to perform functional annotation and pathway enrichment
      analyses for PPI networks, in which P < 0.05 was considered statistically
      significant. RESULTS: Compared to the control samples, the expressions of 42 and
      341 genes were altered in non-metastatic OS and metastatic OS samples,
      respectively. A total of 15 significantly enriched functions were obtained with
      Gene Ontology analysis (P < 0.05). The DEGs were classified and significantly
      enriched in three pathways, including the tricarboxylic acid cycle, lysosome and
      axon guidance. Genes such as HRAS, IDH3A, ATP6ap1, ATP6V0D2, SEMA3F and SEMA3A
      were involved in the enriched pathways. CONCLUSIONS: The hub genes from
      metastatic OS samples are not only bio-markers of OS, but also help to improve
      therapies for OS.

PMID- 24330839
TI  - A moth pheromone brewery: production of (Z)-11-hexadecenol by heterologous co
      expression of two biosynthetic genes from a noctuid moth in a yeast cell factory.
AB  - BACKGROUND: Moths (Lepidoptera) are highly dependent on chemical communication to
      find a mate. Compared to conventional unselective insecticides, synthetic
      pheromones have successfully served to lure male moths as a specific and
      environmentally friendly way to control important pest species. However, the
      chemical synthesis and purification of the sex pheromone components in large
      amounts is a difficult and costly task. The repertoire of enzymes involved in
      moth pheromone biosynthesis in insecta can be seen as a library of specific
      catalysts that can be used to facilitate the synthesis of a particular chemical
      component. In this study, we present a novel approach to effectively aid in the
      preparation of semi-synthetic pheromone components using an engineered vector co
      expressing two key biosynthetic enzymes in a simple yeast cell factory. RESULTS:
      We first identified and functionally characterized a ?11 Fatty-Acyl Desaturase
      and a Fatty-Acyl Reductase from the Turnip moth, Agrotis segetum. The ?11
      desaturase produced predominantly Z11-16:acyl, a common pheromone component
      precursor, from the abundant yeast palmitic acid and the FAR transformed a series
      of saturated and unsaturated fatty acids into their corresponding alcohols which
      may serve as pheromone components in many moth species. Secondly, when we co
      expressed the genes in the Brewer's yeast Saccharomyces cerevisiae, a set of long
      chain fatty acids and alcohols that are not naturally occurring in yeast were
      produced from inherent yeast fatty acids, and the presence of (Z)-11-hexadecenol
      (Z11-16:OH), demonstrated that both heterologous enzymes were active in concert.
      A 100 ml batch yeast culture produced on average 19.5 MUg Z11-16:OH. Finally, we
      demonstrated that oxidized extracts from the yeast cells containing (Z)-11
      hexadecenal and other aldehyde pheromone compounds elicited specific
      electrophysiological activity from male antennae of the Tobacco budworm,
      Heliothis virescens, supporting the idea that genes from different species can be
      used as a molecular toolbox to produce pheromone components or pheromone
      component precursors of potential use for control of a variety of moths.
      CONCLUSIONS: This study is a first proof-of-principle that it is possible to
      "brew" biologically active moth pheromone components through in vitro co
      expression of pheromone biosynthetic enzymes, without having to provide
      supplementary precursors. Substrates present in the yeast alone appear to be
      sufficient.

PMID- 24330841
TI  - The relationship between twin language, twins' close ties, and social competence.
AB  - This study investigated the relationship between twin language, twins' close
      ties, and social competence in a prospective longitudinal study. We hypothesized
      that twins whose tie is close would be more likely to develop a twin language,
      and these twins would be less likely to develop social competence. In addition,
      we hypothesize that some environmental factors, such as having an older sibling,
      preschool attendance, zygosity, and sex are also related to twin language, twins'
      close ties, and social competence. At baseline in 1999 a mailed questionnaire
      survey was conducted, and a follow-up questionnaire was distributed in 2004 among
      958 mothers. As a result, 516 respondents returned the questionnaire (53.9%). In
      this study, we used 261 twin pairs aged from 6 to 12 years (school-age children)
      for analysis, excluding those with missing values. In the present study, we found
      that zygosity and sex were associated with twins' close ties. Having an older
      sibling and preschool attendance did not affect the twins' close tie, twin
      language, or social competence. One of the most important findings was that
      social competence was not affected directly by twins' close tie, but was affected
      when a twin language was found. 

PMID- 24330840
TI  - Dietary fatty acid intake is associated with paraoxonase 1 activity in a cohort
      based analysis of 1,548 subjects.
AB  - BACKGROUND: Paraoxonase 1 (PON1) is a cardioprotective, HDL-associated
      glycoprotein enzyme with broad substrate specificity. Our previous work found
      associations between dietary cholesterol and vitamin C with PON1 activity. The
      goal of this study was to determine the effect of specific dietary fatty acid
      (DFA) intake on PON1 activity. METHODS: 1,548 participants with paraoxonase
      activity measures completed the Harvard Standardized Food Frequency Questionnaire
      to determine their daily nutrient intake over the past year. Eight saturated, 3
      monounsaturated, and 6 polyunsaturated DFAs were measured by the questionnaire.
      To reduce the number of observations tested, only specific fatty acids that were
      not highly correlated (r < 0.8) with other DFAs or that were representative of
      other DFAs through high correlation within each respective group (saturated,
      monounsaturated, or polyunsaturated) were retained for analysis. Six specific DFA
      intakes - myristic acid (14 carbon atoms, no double bonds - 14:0), oleic acid
      (18:1), gadoleic acid (20:1), alpha-linolenic acid (18:3), arachidonic acid
      (20:4), and eicosapentaenoic acid (20:5) - were carried forward to stepwise
      linear regression, which evaluated the effect of each specific DFA on covariate
      adjusted PON1 enzyme activity. RESULTS: Four of the 6 tested DFA intakes -
      myristic acid (p = 0.038), gadoleic acid (p = 6.68 * 10(-7)), arachidonic acid (p
      = 0.0007), and eicosapentaenoic acid (p = 0.013) - were independently associated
      with covariate-adjusted PON1 enzyme activity. Myristic acid, a saturated fat, and
      gadoleic acid, a monounsaturated fat, were both positively associated with PON1
      activity. Both of the tested polyunsaturated fats, arachidonic acid and
      eicosapentaenoic acid, were negatively associated with PON1 activity.
      CONCLUSIONS: This study presents the largest cohort-based analysis of the
      relationship between dietary lipids and PON1 enzyme activity. Further research is
      necessary to elucidate and understand the specific biological mechanisms, whether
      direct or regulatory, through which DFAs affect PON1 activity.

PMID- 24330842
TI  - TRAPID: an efficient online tool for the functional and comparative analysis of
      de novo RNA-Seq transcriptomes.
AB  - Transcriptome analysis through next-generation sequencing technologies allows the
      generation of detailed gene catalogs for non-model species, at the cost of new
      challenges with regards to computational requirements and bioinformatics
      expertise. Here, we present TRAPID, an online tool for the fast and efficient
      processing of assembled RNA-Seq transcriptome data, developed to mitigate these
      challenges. TRAPID offers high-throughput open reading frame detection,
      frameshift correction and includes a functional, comparative and phylogenetic
      toolbox, making use of 175 reference proteomes. Benchmarking and comparison
      against state-of-the-art transcript analysis tools reveals the efficiency and
      unique features of the TRAPID system. TRAPID is freely available at
      http://bioinformatics.psb.ugent.be/webtools/trapid/. 

PMID- 24330844
TI  - No news without new scientific ideas.
AB  - In this editorial, it is strongly advocated that a change of policy is warranted
      in order to prevent neuroscience from becoming a waste of time and money in the
      21st century. Repeating the same trick in different patient populations and
      perusing the scientific literature seems to currently be the backbone of medical
      science. However, this approach does not provide knowledge on how the brain works
      or how specific dysfunctions result in specific diseases. Therefore, earlier
      findings should, first, be combined to develop new theories on the mechanics of
      the mind, and, second, these new ideas should be tested in well-designed
      experiments. 

PMID- 24330843
TI  - Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and
      poor prognosis in gastric carcinoma.
AB  - BACKGROUND: PRL-3 is a member of phosphatases of regenerating liver family,
      characterized by phosphatase active domain and C-terminal prenylation motif.
      Overexpression of PRL-3 has been implicated in multiple cancers. Here we examined
      the clinical significance of PRL-3 in gastric cancer together with its metastatic
      biological functions utilizing different structural mutants. METHODS: PRL-3
      expression was analyzed immunohistochemically in 196 gastric cancer patients and
      21 cases of liver metastasis. A series of wild type PRL-3 or its mutant plasmids
      were expressed in BGC823 cells to investigate the relationship between its
      catalytic activity, cellular localization and metastatic potential in vitro.
      RESULTS: Positive staining of PRL-3 was observed in 19.4% (38/196) gastric cancer
      tissues compared with 76.2% (16/21) in liver metastasis. Statistical analysis
      revealed that PRL-3 expression correlated with lymph node metastasis and vascular
      invasion (P<0.05). Patients with high PRL-3 expression showed poorer 5-year
      overall survival (P=0.011). Wild type PRL-3 expressing cells resulted in enhanced
      migration and invasion ability, which were greatly crippled in form of PRL
      3(C104S) or PRL-3(DeltaCAAX) mutants accompanied with its alteration in
      subcellular localization. CONCLUSIONS: Metastasis associated protein PRL-3 may
      serve as a potential prognostic biomarker in human gastric cancer. Both the
      phosphatase catalytic activity and cellular localization are critical for its
      function.

PMID- 24330845
TI  - Altered white-matter architecture in treatment-naive adolescents with clinical
      depression.
AB  - BACKGROUND: Depressive disorders are highly prevalent in adolescence and confer a
      heightened risk of recurrence in adulthood. Insight into the developmental
      neurocircuitry of depression could advance our understanding of depression and
      aid the development of effective treatment strategies. Whereas white-matter (WM)
      abnormalities are strongly implicated in adult depression, we still lack a firm
      understanding of WM architecture in adolescent depression. Using diffusion tensor
      imaging (DTI), we set out to investigate WM microstructure in a sample of
      clinically depressed adolescents relative to matched controls. METHOD: We
      employed tract-based spatial statistics (TBSS) to examine WM microstructure in 25
      treatment-naive adolescents with clinical depression relative to 21 matched
      controls. Using TBSS, we examined fractional anisotropy (FA), axial diffusivity
      (AD), radial diffusivity (RD) and mean diffusivity (MD). Threshold-free cluster
      enhancement (TFCE) with family-wise error (FWE) correction was used to control
      for multiple comparisons. RESULTS: Our analysis revealed abnormal WM
      microstructure in clinically depressed adolescents. More specifically, whole
      brain analysis revealed that patients had lower FA values in the body of the
      corpus callosum (CC), coupled with elevated RD and MD, and preserved AD.
      Conversely, region-of-interest analysis revealed that patients had higher FA
      values in the uncinate fasciculus (UF), coupled with elevated AD, reduced RD and
      preserved MD. CONCLUSIONS: In line with neurocircuitry models of depression, our
      findings suggest that WM abnormalities within pathways facilitating cognitive and
      emotional functioning are involved in the pathophysiology of depression.
      Importantly, our findings show that these WM abnormalities are already present
      early in the course of the disorder.

PMID- 24330846
TI  - High risk sexual behaviors are associated with sexual violence among a cohort of
      women in Durban, South Africa.
AB  - BACKGROUND: Studies show Gender Based Violence (GBV) to be significantly
      associated with risky sexual behaviour. In South Africa the incidence of GBV is
      reportedly high, and there is a strong argument for GBV to be a driver of HIV
      infection rates. This study describes the prevalence of Forced Sex (FS)
      experiences of women who enrolled into an HIV biomedical intervention study, and
      its association with risky sexual behaviour. FINDINGS: In this study,
      sociodemographic and behavioural data from women enrolled in the CarraguardTM
      trial, were assessed in relation to FS using logistic regression. The results
      indicated that 193/1485 (13%) of women reported ever experiencing FS at the
      screening visit. Women who were 30 years and older; reported having sex for cash;
      multiple partners; changing partners during the trial; inconsistent condom use
      during the trial; and 3 or more sex acts in the 2 weeks prior to screening, were
      significantly more likely to have experienced forced sex. CONCLUSIONS: The
      results of this study are broadly consistent with those found in other studies
      and are similar in profile to women at higher risk for HIV acquisition in our
      setting. This study indicates a need for GBV prevention to be integrated with HIV
      prevention programmes.

PMID- 24330847
TI  - Induction of apoptosis by 4-(3-(tert-butylamino)imidazo[1,2-alpha]pyridine-2-yl)
      benzoic acid in breast cancer cells via upregulation of PTEN.
AB  - We have previously reported that 4-(3-(tert-butylamino)imidazo[1,2-alpha]pyridine
      2-yl)benzoic acid, a bicyclic N-fused aminoimidazoles derivative (BNFA-D),
      possesses anticancer potentiality against breast and kidney cancer cells with
      minimal toxicities to corresponding normal cells. Here, we explored the mechanism
      of action of BNFA-D in breast cancer cells using multiple cell-based assays such
      as MTT, DAPI, FACS, Western blot, and immunoprecipitation. BNFA-D caused
      apoptosis by upregulating PTEN leading to inhibition of Wnt/TCF signaling cascade
      and arresting S phase in breast cancer cells. Expression levels of beta-catenin,
      cyclin D1, C-MYC, and phospho-AKT (Ser(473)) decreased with simultaneous increase
      in the levels of GSK3beta, CK1, and PTEN in BNFA-D-treated MCF-7 cells.
      Interestingly, silencing of PTEN in breast cancer cells reversed the phenomenon
      of Wnt/TCF signaling cascade inhibition after BNFA-D treatment.

PMID- 24330848
TI  - Anti-inflammatory effect of full-length adiponectin and proinflammatory effect of
      globular adiponectin in esophageal adenocarcinoma cells.
AB  - Adiponectin, an adipocyte-derived hormone with anti-inflammatory and antitumor
      activity, inhibits esophageal adenocarcinoma (EAC) cell proliferation and induces
      apoptosis. Chronic inflammation is a key process involved in initiation and
      progression of EAC, but the roles and mechanisms of adiponectin in inflammation
      have not been fully understood in EAC. We aimed to analyze the effects of two
      types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g
      Ad), on inflammatory factors' expression and explore the roles of ROS/NF-kappaB
      signaling pathway in adiponectin-regulated inflammation in EAC cells. It was
      found that f-Ad and g-Ad differently regulated both mRNA and protein levels of
      TNF-alpha, IL-8, and IL-6 in a dose-dependent manner in OE19 cells. g-Ad
      apparently induced TNF-alpha, IL-8, and IL-6 production, which was inhibited by
      PDTC or NAC, and increased intracellular ROS levels and NF-kappaB p65 activation,
      whereas f-Ad significantly suppressed production of inflammatory factors and NF
      kappaB p65 activation and also decreased the intracellular ROS levels. In
      conclusion, the study demonstrated that g-Ad exerts a proinflammatory effect
      whereas f-Ad appears to induce an anti-inflammatory effect in a ROS/NF-kappaB
      dependent manner in OE19 cells.

PMID- 24330849
TI  - Restoration of INK4a/ARF gene inhibits cell growth and cooperates with imatinib
      mesylate in Philadelphia chromosome-positive leukemias.
AB  - VSV-G-pseudotyped lentiviral vectors expressing p16(INK4a) or p14(ARF) were used
      to infect at high-efficiency Philadelphia chromosome (Ph)-positive leukemia cell
      lines lacking endogenous transcripts. Restoration of p16(INK4a) accumulated cells
      in the G0/G1 phase of cell cycle and restoration of p14(ARF) induced their
      apoptosis, followed by significant growth inhibition. Transduction of primary
      blast cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph
      positive acute lymphoblastic leukemia (ALL) with p16(INK4a) or p14(ARF) virus
      also resulted in cell growth inhibition and/or apoptosis with a patient-to
      patient variation, whereas clonal growth and differentiation of cord blood
      progenitor cells were not affected by enforced expression of INK4a/ARF.
      Furthermore, upon viral transduction at low multiplicity of infection, INK4a/ARF
      potentiated the effect of imatinib mesylate on Ph-positive leukemia cell lines in
      an additive but not synergistic manner. These results suggest that INK4a/ARF
      protein-mimetic agents may be promising options for Ph-positive leukemias in
      combination with imatinib mesylate. 

PMID- 24330850
TI  - Overexpression of Bmi-1 induces the malignant transformation of gastric
      epithelial cells in vitro.
AB  - Oncogene Bmi-1 (B-cell-specific Moloney murine leukemia virus integration site 1)
      has attracted much attention for its involvement in the initiation of a variety
      of tumors. Our previous study showed that Bmi-1 was highly expressed in gastric
      cancer and correlated with patient prognosis. However, whether aberrant Bmi-1
      expression was critical for the transformation of gastric epithelial cells
      remains unknown. In this study, we stably expressed Bmi-1 in a human gastric
      epithelial immortalized cell line, GES-1. The overexpression of Bmi-1 promoted
      cell growth and proliferation, inhibited apoptosis, enhanced clone formation
      capability, possessed the characteristics of anchorage-independent growth, and
      increased migration and invasion abilities. Therefore, our findings demonstrated
      that ectopic expression of Bmi-1 played an important role in the malignant
      transformation of gastric epithelial cells. 

PMID- 24330851
TI  - Inhibition of cell proliferation and increase of chemosensitivity by simultaneous
      knockdown of XIAP and survivin in pancreatic carcinoma cells.
AB  - At present, classic therapies provide limited benefits to the survival of
      patients with pancreatic cancer. However, clinically available gene therapy
      strategies have not been well established. This study investigates the effect of
      shRNA-mediated inhibition of XIAP and survivin expression on the proliferation,
      apoptosis, and chemosensitivity of pancreatic cancer cells. Stable inhibition of
      XIAP and survivin expression in SW1990 and Panc-1 pancreatic cancer cells was
      established by lentivirus-carried shRNAs. The mRNA and protein expression of XIAP
      and survivin were detected by real-time PCR and Western blot, respectively. Cell
      proliferation was measured by MTT assay, and apoptosis was detected by caspase
      3/7 activity and Hoechst33342 staining. The lentivirus-carried shRNA
      significantly inhibited XIAP and survivin expression. Simultaneous inhibition of
      XIAP and survivin expression in pancreatic cells significantly reduced cell
      proliferation, increased caspase-3/7 activity, and increased cell sensitization
      to 5-FU and gemcitabine treatments compared to inhibition of XIAP or survivin
      expression alone. However, simultaneous silencing of XIAP and survivin showed no
      significant difference in inducing cell apoptosis compared to silencing of XIAP
      or survivin expression alone. Simultaneous inhibition of XIAP and survivin
      expression may be an effective strategy for gene therapy of pancreatic cancer.

PMID- 24330852
TI  - In vitro characterization of stem cell-like properties of drug-resistant colon
      cancer subline.
AB  - The objective of this study was to investigate the stem cell-like properties of
      drug-resistant colon cancer cells. Oxaliplatin was used to induce the drug
      resistant subline of HCT116(p53+/+) cell line. The stem cell-like characteristics
      of the drug-resistant subline were assayed for the proliferation capacity, cell
      cycle, adhesion, invasion, multiple drug resistance, and clone sphere formation
      capacity. The expression of ABCG2 (ATP-binding cassette superfamily G member 2)
      and "stemness" indicators SOX2 (SRY-related HMG box-containing transcription
      factor-2) and OCT4 (octamer-binding transcription factor 4) was determined by
      Western blot. We established the HCT116(p53+/+)-oxaliplatin subline
      (HCT116(p53+/+)OXA), which was resistant to oxaliplatin with a resistance index
      (RI) of 3.03 +/- 0.14. The HCT116(p53+/+)OXA was also resistant to Taxol, showing
      lower proliferation, higher adhesion and invasion ability, greater proportion of
      G0/G1 phase, and higher sphere-forming capacity than its parental cells. SOX2,
      OCT4, and ABCG2 were expressed at higher levels in drug-resistant cells than in
      their parental cells. We verified that the HCT116(p53+/+)OXA was enriched with
      cancer stem cell properties and provided an ideal cell model for drug-resistance
      study.

PMID- 24330853
TI  - Involvement of oncogenic protein beta-catenin in LPS-induced cytotoxicity in
      mouse mononuclear leukemia RAW 264.7 cells.
AB  - A toll-like receptor 4 (TLR-4) ligand, lipopolysaccharide (LPS) not only
      activates expression and secretion of inflammatory cytokines, but it also often
      shows toxicity in monocytes. Whether an oncogenic protein, beta-catenin, is
      positively involved in LPS-induced cytotoxicity in a mouse leukemic monocyte cell
      line, RAW 264.7, was examined. TWS119, a GSK-3beta inhibitor, increased LPS
      induced beta-catenin accumulation in the nucleus and augmented LPS-induced
      cytotoxicity. Cardamonin, a beta-catenin inhibitor, inhibited LPS-induced beta
      catenin accumulation in the nucleus and reduced LPS-induced cytotoxicity. To
      confirm that beta-catenin is involved in LPS-induced cytotoxicity, silencing of
      beta-catenin expression by siRNA was carried out. The results were that knockdown
      of beta-catenin reduced LPS-induced cytotoxicity. Interestingly, Cardamonin
      treatment or beta-catenin silencing reduced LPS-induced endoplasmic reticulum
      (ER) stress responses such as PERK and e1F-2alpha phosphorylation and CHOP
      expression. Moreover, TWS119 increased LPS-induced ER stress responses. On the
      basis of these results, the oncogenic protein beta-catenin is considered to be
      positively involved in LPS-induced cytotoxicity, possibly by downregulating ER
      stress responses. 

PMID- 24330854
TI  - Impact of chronic diuretic treatment on glucose homeostasis.
AB  - BACKGROUND: The use of diuretics for hypertension has been associated with
      unfavorable changes in cardiovascular risk factors, such as uric acid and glucose
      tolerance, though the findings in the literature are contradictory. METHODS: This
      study investigated whether diuretic use is associated with markers of metabolic
      and cardiovascular risk, such as insulin-resistance and uric acid, in a cohort of
      adults without known diabetes and/or atherosclerotic cardiovascular disease. Nine
      hundred sixty-nine randomly selected participants answered a questionnaire on
      clinical history and dietary habits. Laboratory blood measurements were obtained
      in 507 participants. RESULTS: Previously undiagnosed type 2 diabetes was
      recognized in 4.2% of participants who were on diuretics (n = 71), and in 2% of
      those who were not (n = 890; P = 0.53). Pre-diabetes was diagnosed in 38% of
      patients who were on diuretics, and in 17.4% (P < 0.001) of those who were not.
      Multivariate analysis showed that insulin-resistance (HOMA-IR) was associated
      with the use of diuretics (P = 0.002) independent of other well-known
      predisposing factors, such as diet, physical activity, body mass index, and waist
      circumference. The use of diuretics was also independently associated with
      fasting plasma glucose concentrations (P = 0.001) and uric acid concentrations (P
      = 0.01). CONCLUSIONS: The use of diuretics is associated with insulin-resistance
      and serum uric acid levels and may contribute to abnormal glucose tolerance.

PMID- 24330855
TI  - Effects of exposure to a cafeteria diet during gestation and after weaning on the
      metabolism and body weight of adult male offspring in rats.
AB  - In the present study, we investigated whether maternal exposure to a cafeteria
      diet affects the metabolism and body composition of offspring and whether such an
      exposure has a cumulative effect during the lifetime of the offspring. Female
      rats were fed a control (CON) or a cafeteria (CAF) diet from their own weaning to
      the weaning of their offspring. At 21 d of age, male offspring were divided into
      four groups by diet during gestation and after weaning (CON-CON, CON-CAF, CAF-CON
      and CAF-CAF). Blood was collected from dams (after weaning) and pups (at 30 and
      120 d of age) by decapitation. CAF dams had significantly greater body weight and
      adipose tissue weight and higher concentrations of total cholesterol, insulin and
      leptin than CON dams (Student's t test). The energy intake of CAF rats was higher
      than that of CON rats regardless of the maternal diet (two-way ANOVA). Litters
      had similar body weights at weaning and at 30 d of age, but at 120 d, CON-CAF
      rats were heavier. At both ages, CAF rats had greater adipose tissue weight than
      CON rats regardless of the maternal diet, and the concentrations of TAG and
      cholesterol were similar between the two groups, as were blood glucose
      concentrations at 30 d of age. However, at 120 d of age, CAF rats were
      hyperglycaemic, hyperinsulinaemic and hyperleptinaemic regardless of the maternal
      diet. These findings suggest that maternal obesity does not modulate the
      metabolism of male offspring independently, modifying body weight only when
      associated with the intake of a cafeteria diet by the offspring.

PMID- 24330856
TI  - The progress of targeted therapy in advanced gastric cancer.
AB  - Although palliative chemotherapy has been shown to prolong survival and improve
      quality of life, the survival of advanced gastric cancer (AGC) patients remains
      poor. With the advent of targeted therapy, many molecular targeted agents have
      been evaluated in clinical studies. Trastuzumab, an anti-HER2 monoclonal
      antibody, has shown activity against HER2-positive AGC and becomes the first
      targeted agent approved in AGC. Drugs that target epidermal growth factor
      receptor, including monoclonal antibody and tyrosine kinase inhibitor, do not
      bring survival benefit to patients with AGC. Additionally, vascular endothelial
      growth factor inhibitors are also under investigation. Ramucirumab has shown
      promising result. Other targeted agents are in preclinical or early clinical
      development, such as mammalian target of rapamycinm inhibitors and c-MET
      inhibitors. 

PMID- 24330858
TI  - Establishment of a bortezomib-resistant Chinese human multiple myeloma cell line:
      MMLAL.
AB  - BACKGROUND: A new human myeloma cell line, MMLAL, was established from the
      myelomatous pleural effusion of a 73-year-old Chinese patient suffering from
      symptomatic International stage III IgG/lambda myeloma. After a brief period of
      complete remission, he developed aggressive systemic relapse complicated by
      malignant pleural effusion with exclusive plasma cell infiltration. His disease
      remained chemo-refractory, and died six months after relapse. METHODS: Purified
      mononuclear cells from the pleural effusion of the patient were cultured in the
      presence of IL-6. Continually growing cells were characterized by morphological,
      immunophenotypic, cytogenetic, fluorescence in situ hybridization (FISH) and TP53
      mutation analyses. Cell proliferation was measured and compared with other
      myeloma cell lines by cell counting at day 3, 6, 9, and 12. Drug resistance
      against bortezomib, a proteasome inhibitor approved as a frontline chemotherapy
      for eligible myeloma patients, was evaluated and compared with other myeloma cell
      lines by MTT assay. RESULTS: Immunophenotypic analysis of the myeloma cells
      confirmed strong expression of plasma cell markers CD38 and CD138 but not T-cell
      or natural killer-cell marker CD56. Cytogenetic analysis of the myeloma cells
      showed a hypodiploid composite karyotype including loss of chromosome 13 and 17
      or deletion of the short arm of chromosome 17, i.e. del(17p), in the form of
      isochromosome 17q10. FISH confirmed a hypodiploid karyotype with TP53 deletion
      but absence of t(4;14). Sequencing analysis of the TP53 gene indicated absence of
      mutation. Cell counting revealed that the maximum viable cell density was about
      2.5 X 106 cells/ml. Upon bortezomib treatment, MTT assay reported an IC50 of
      72.17nM, suggesting a strong bortezomib resistance. CONCLUSION: A hypodiploid
      with loss of chromosome 13 and loss or del(17p) human myeloma cell line, MMLAL,
      was established from the pleural effusion of a Chinese myeloma patient.

PMID- 24330857
TI  - Interactions of peptide triazole thiols with Env gp120 induce irreversible
      breakdown and inactivation of HIV-1 virions.
AB  - BACKGROUND: We examined the underlying mechanism of action of the peptide
      triazole thiol, KR13 that has been shown previously to specifically bind gp120,
      block cell receptor site interactions and potently inhibit HIV-1 infectivity.
      RESULTS: KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide
      triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein
      release. The resulting virion post virolysis had an altered morphology, contained
      no gp120, but retained gp41 that bound to neutralizing gp41 antibodies.
      Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks
      formation of the gp41 6-helix bundle during membrane fusion, while no inhibition
      of p24 release occurred for enfuvirtide-resistant virus. KR13 thus appears to
      induce structural changes in gp41 normally associated with membrane fusion and
      cell entry. The HIV-1 p24 release induced by KR13 was observed in several clades
      of HIV-1 as well as in fully infectious HIV-1 virions. CONCLUSIONS: The antiviral
      activity of KR13 and its ability to inactivate virions prior to target cell
      engagement suggest that peptide triazole thiols could be highly effective in
      inhibiting HIV transmission across mucosal barriers and provide a novel probe to
      understand biochemical signals within envelope that are involved in membrane
      fusion.

PMID- 24330859
TI  - Chromosome territories reposition during DNA damage-repair response.
AB  - BACKGROUND: Local higher-order chromatin structure, dynamics and composition of
      the DNA are known to determine double-strand break frequencies and the efficiency
      of repair. However, how DNA damage response affects the spatial organization of
      chromosome territories is still unexplored. RESULTS: Our report investigates the
      effect of DNA damage on the spatial organization of chromosome territories within
      interphase nuclei of human cells. We show that DNA damage induces a large-scale
      spatial repositioning of chromosome territories that are relatively gene dense.
      This response is dose dependent, and involves territories moving from the nuclear
      interior to the periphery and vice versa. Furthermore, we have found that
      chromosome territory repositioning is contingent upon double-strand break
      recognition and damage sensing. Importantly, our results suggest that this is a
      reversible process where, following repair, chromosome territories re-occupy
      positions similar to those in undamaged control cells. CONCLUSIONS: Thus, our
      report for the first time highlights DNA damage-dependent spatial reorganization
      of whole chromosomes, which might be an integral aspect of cellular damage
      response.

PMID- 24330860
TI  - Daytime sleepiness associated with lurasidone and quetiapine XR: results from a
      randomized double-blind, placebo-controlled trial in patients with schizophrenia.
AB  - OBJECTIVE: The aim of this analysis was to compare the effects of 2 atypical
      antipsychotic agents, lurasidone (80 mg/d or 160 mg/d) and quetiapine XR (600
      mg/d), on daytime alertness, and to evaluate the effects of daytime sleepiness on
      treatment outcomes in patients with an acute exacerbation of schizophrenia.
      METHODS: Patients who met Diagnostic and Statistical Manual of Mental Disorders,
      4th edition, text revision (DSM-IV-TR) criteria for schizophrenia were randomized
      to 6 weeks of double-blind treatment with fixed doses of lurasidone 80 mg/d (n =
      125), lurasidone 160 mg/d (n = 121), quetiapine XR 600 mg/d (n = 119), or placebo
      (n = 121), all dosed once daily in the evening, with food. Daytime sleepiness was
      assessed using the Epworth Sleepiness Scale (ESS). RESULTS: Daytime sleepiness
      improved in the lurasidone and placebo-treated groups but worsened in the
      quetiapine XR treatment group when compared to placebo (p = 0.001) and to either
      dose of lurasidone (both p < 0.01). Sedation associated with quetiapine XR
      treatment mediated an improvement in agitation [assessed by the Positive and
      Negative Syndrome Scale-Excitement (PANSS-EC) subscale] and a worsening in
      functional capacity [assessed by the University of California-San Diego (UCSD)
      Performance-Based Skills Assessment-Brief Version (UPSA-B) total score]; these
      mediating relationships were not observed for the lurasidone or placebo treatment
      groups. CONCLUSION: In this 6-week double-blind study, treatment with lurasidone
      80 mg or 160 mg, administered once daily in the evening, was associated with a
      reduction in daytime sleepiness similar in magnitude to placebo, while quetiapine
      XR 600 mg/d was associated with a significant increase in daytime sleepiness,
      compared to both lurasidone dose groups and placebo. Daytime sleepiness was
      associated with improvement in agitation and worsening in functional capacity for
      quetiapine XR, but not lurasidone or placebo-treated patients.

PMID- 24330861
TI  - Community cooperation as a disaster medicine competency.

PMID- 24330862
TI  - epic3: national evidence-based guidelines for preventing healthcare-associated
      infections in NHS hospitals in England.
AB  - National evidence-based guidelines for preventing healthcare-associated
      infections (HCAI) in National Health Service (NHS) hospitals in England were
      originally commissioned by the Department of Health and developed during 1998
      2000 by a nurse-led multi-professional team of researchers and specialist
      clinicians. Following extensive consultation, they were first published in
      January 2001(1) and updated in 2007.(2) A cardinal feature of evidence-based
      guidelines is that they are subject to timely review in order that new research
      evidence and technological advances can be identified, appraised and, if shown to
      be effective for the prevention of HCAI, incorporated into amended guidelines.
      Periodically updating the evidence base and guideline recommendations is
      essential in order to maintain their validity and authority. The Department of
      Health commissioned a review of new evidence and we have updated the evidence
      base for making infection prevention and control recommendations. A critical
      assessment of the updated evidence indicated that the epic2 guidelines published
      in 2007 remain robust, relevant and appropriate, but some guideline
      recommendations required adjustments to enhance clarity and a number of new
      recommendations were required. These have been clearly identified in the text. In
      addition, the synopses of evidence underpinning the guideline recommendations
      have been updated. These guidelines (epic3) provide comprehensive recommendations
      for preventing HCAI in hospital and other acute care settings based on the best
      currently available evidence. National evidence-based guidelines are broad
      principles of best practice that need to be integrated into local practice
      guidelines and audited to reduce variation in practice and maintain patient
      safety. Clinically effective infection prevention and control practice is an
      essential feature of patient protection. By incorporating these guidelines into
      routine daily clinical practice, patient safety can be enhanced and the risk of
      patients acquiring an infection during episodes of health care in NHS hospitals
      in England can be minimised. 

PMID- 24330863
TI  - 'Ethnicity as a predictor of detention under the Mental Health Act': a response
      to Singh et al.

PMID- 24330865
TI  - Ewing's sarcoma arising from the adrenal gland in a young male: a case report.
AB  - BACKGROUND: Ewing's sarcoma uncommonly arises from extraosseous soft tissue or
      parenchymal organs. Primary adrenal Ewing's Sarcoma, although very rare, is
      extremely aggressive and commonly fatal. CASE PRESENTATION: A 17 year old
      Pakistani male was referred to the outpatient oncology clinic at our center with
      a three month history of concomitant pain, swelling and dragging sensation in the
      right hypochondrium. Abdominal examination revealed a large, firm mass in the
      right hypochondrium extending into the right lumbar region and epigastrium. His
      genital exam was unremarkable and there were no stigmata of hepatic or adrenal
      disease.Computed tomography scans revealed a large peripherally enhancing mass in
      the hepatorenal area, biopsy of which showed a neoplastic lesion composed of
      small round blue cells which exhibited abundance of glycogen and stained
      diffusely positive for CD99 (MIC2 antigen). Fluorescence in situ hybridization
      demonstrated gene rearrangement at chromosome 22q12 which confirmed the diagnosis
      of Ewing's sarcoma. Staging scans revealed pulmonary metastasis and hence he was
      commenced on systemic chemotherapy. CONCLUSION: This case report highlights the
      importance of keeping Ewing's sarcoma in mind when a young patient presents with
      a large non-functional adrenal mass.

PMID- 24330864
TI  - Genetic CJD with a novel E200G mutation in the prion protein gene and comparison
      with E200K mutation cases.
AB  - A novel point mutation resulting in a glutamate-to-glycine substitution in PRNP
      at codon 200, E200G with codon 129 MV polymorphism (cis valine) and type 2 PrPSc
      was identified in a patient with a prolonged disease course leading to pathology
      proven Jakob-Creutzfeldt disease. Despite the same codon as the most common
      genetic form of human PRNP mutation, E200K, this novel mutation (E200G) presented
      with a different clinical and pathological phenotype, including prolonged
      duration, large vacuoles, no vacuolation in the hippocampus, severe neuronal loss
      in the thalamus, mild cerebellar involvement, and abundant punctate linear and
      curvilinear deposition of PrPSc in synaptic boutons and axonal terminals along
      the dendrites. 

PMID- 24330866
TI  - The spliceosomal catalytic core arose in the RNA world... or did it?
AB  - A new study adds to the evidence for a common evolutionary origin of the
      spliceosome and group II introns, but RNA-world questions remain. 

PMID- 24330867
TI  - Improving public health preparedness capacity measurement: development of the
      local health department preparedness capacities assessment survey.
AB  - OBJECTIVE: To address limitations in measuring the preparedness capacities of
      health departments, we developed and tested the Local Health Department
      Preparedness Capacities Assessment Survey (PCAS). METHODS: Preexisting
      instruments and a modified 4-cycle Delphi panel process were used to select
      instrument items. Pilot test data were analyzed using exploratory factor
      analysis. Kappa statistics were calculated to examine rater agreement within
      items. The final instrument was fielded with 85 North Carolina health departments
      and a national matched comparison group of 248 health departments. RESULTS:
      Factor analysis identified 8 initial domains: communications, surveillance and
      investigation, plans and protocols, workforce and volunteers, legal
      infrastructure, incident command, exercises and events, and corrective action.
      Kappa statistics and z scores indicated substantial to moderate agreement among
      respondents in 7 domains. Cronbach alpha coefficients ranged from 0.605 for legal
      infrastructure to 0.929 for corrective action. Mean scores and standard
      deviations were also calculated for each domain and ranged from 0.41 to 0.72,
      indicating sufficient variation in the sample to detect changes over time.
      CONCLUSION: The PCAS is a useful tool to determine how well health departments
      are performing on preparedness measures and identify opportunities for future
      preparedness improvements. Future survey implementation will incorporate recent
      Centers for Disease Control and Prevention's Public Health Preparedness
      Capabilities: National Standards for State and Local Planning.

PMID- 24330869
TI  - [Some argument in the field of thyroid neoplasms surgery].

PMID- 24330868
TI  - Effectiveness of lurasidone in schizophrenia or schizoaffective patients switched
      from other antipsychotics: a 6-month, open-label, extension study.
AB  - OBJECTIVE: To evaluate the long-term safety and tolerability of lurasidone in
      schizophrenia and schizoaffective disorder patients switched to lurasidone.
      METHOD: Patients in this multicenter, 6-month open-label, flexible-dose,
      extension study had completed a core 6-week randomized trial in which clinically
      stable, but symptomatic, outpatients with schizophrenia or schizoaffective
      disorder were switched to lurasidone. Patients started the extension study on
      treatment with the same dose of lurasidone taken at study endpoint of the 6-week
      core study; following this, lurasidone was flexibly dosed (40-120 mg/day), if
      clinically indicated, starting on Day 7 of the extension study. The primary
      safety endpoints were the proportion of patients with treatment emergent adverse
      events (AEs), serious AEs, or who discontinued due to AEs. Secondary endpoints
      included metabolic variables and measures of extrapyramidal symptoms and
      akathisia, as well as the Positive and Negative Syndrome Scale (PANSS), Clinical
      Global Impressions-Severity (CGI-S), and the Calgary Depression Scale for
      Schizophrenia (CDSS). The study was conducted from August 2010 to November 2011.
      RESULTS: Of the 198 patients who completed the 6-week core study, 149 (75.3%)
      entered the extension study and 148 received study medication. A total of 98
      patients (65.8%) completed the 6-month extension study. Lurasidone 40, 80, and
      120 mg were the modal daily doses for 19 (12.8%), 65 (43.9%), and 64 (43.2%) of
      patients, respectively. Overall mean (SD) daily lurasidone dose was 102.0 mg
      (77.1). The most commonly reported AEs were insomnia (13 patients [8.8%]), nausea
      (13 patients [8.8%]), akathisia (12 patients [8.1%]), and anxiety (9 patients
      [6.1%]). A total of 16 patients (10.8%) had at least one AE leading to
      discontinuation from the study. Consistent with prior studies of lurasidone,
      there was no signal for clinically relevant adverse changes in body weight,
      lipids, glucose, insulin, or prolactin. Movement disorder rating scales did not
      demonstrate meaningful changes. Treatment failure (defined as any occurrence of
      discontinuation due to insufficient clinical response, exacerbation of underlying
      disease, or AE) was observed for 19 patients (12.8% of patients entering) and
      median time to treatment failure was 58 days (95% CI 22-86). The discontinuation
      rate due to any cause was 50/148 (33.8%), and median time to discontinuation was
      62 days (95% CI 30-75). The mean PANSS total score, mean CGI-S score, and mean
      CDSS score decreased consistently from core study baseline across extension
      visits, indicating an improvement in overall condition. CONCLUSIONS: In this 6
      month, open-label extension study, treatment with lurasidone was generally well
      tolerated with sustained improvement in efficacy measures observed in outpatients
      with schizophrenia or schizoaffective disorder who had switched to lurasidone
      from a broad range of antipsychotic agents.

PMID- 24330870
TI  - [Management of thyroid carcinoma with metastases in the upper mediastinum and
      axillary area].
AB  - OBJECTIVE: To investigate the clinical characteristics and management of thyroid
      carcinoma with the upper mediastinal and axillary metastasis. METHODS: Six cases
      of thyroid carcinomas with metastases to mediastinum and axillary, in addition to
      the neck, undergoing surgeries from 2006 to 2011 were reviewed. Five cases was
      papillary carcinoma and one was follicular carcinoma. Of six patients, five
      underwent surgical treatment at least one time previously and one of them
      received a radiotherapy with total dose of 60 Gy. (131)I treatment and thyroxine
      were used postoperatively in all cases. RESULTS: The numbers of metastatic nodes
      in the axillary were 2/7, 3/12, 2/6, 1/5, 3/7 and 3/10 respectively, while the
      numbers in the upper mediastinum ranged from 2 to 6, with a 4.3 average, a
      metastatic lymph node in the retropharyngeal space was also found in one patient.
      Horner's sign occurred in three cases, temporary hypocalcemia in two cases and
      chylous fistula in one case. No injury to the recurrent laryngeal nerve or to
      important vessels. Neck or lower mediastinum recurrence and new lung metastasis
      occurred in three cases separately. No recurrence in the upper mediastinum or
      axillary area was found with the follow-up of 23-77 months. One died of heart
      disease 4 years after operation. CONCLUSION: The surgical treatment of node
      metastases in the upper mediastinum and axillary from the well-differentiated
      thyroid cancer is safe and has a promising outcome.

PMID- 24330871
TI  - [Minimally invasive endoscopy-assisted neck dissection to treat lateral cervical
      metastasis of thyroid papillary carcinoma].
AB  - OBJECTIVE: Traditional open surgery for lateral neck dissection for patients with
      papillary thyroid carcinoma (PTC) leaves an unsightly scar. It is necessary to
      apply small incision to complete lateral neck dissection with endoscopy-technique
      for PTC and to evaluate its feasibility and safety. METHODS: Between March 2010
      and May 2011, 6 cases of PTC with no definite lymph node metastasis at level II
      IV and 12 cases of PTC at T1-T4 with definite lymph node metastasis at level II-V
      received minimally invasive endoscopy-assisted lateral neck dissection. After
      accomplishing thyroidectomy and central compartment dissection, ipsilateral level
      II-IV,VI orII-VI dissection via small neck incision was performed. RESULTS: This
      procedure was carried out successfully in all 18 patients. The incision was 5 cm
      every patient. Postoperative pT1 was 5 cases, pT2 5 cases, pT3 6 cases, pT4 2
      cases, pN0 5 cases, N1b 13 cases. Mean operative time for lateral neck dissection
      was 3.6 hours (ranging 2.5-5.0 hours). No significant blood loss or complications
      occurred. Thirteen patients showed lymph node metastases in both central or
      lateral neck. The mean number of harvested nodes was 33.1 (ranging 16-61). No
      residual or recurrent disease was found in 2-3 years follow-up time. CONCLUSION:
      Minimally invasive video-assisted comprehensive neck dissection for metastatic
      papillary thyroid carcinoma is feasible and safe with excellent cosmetic results.

PMID- 24330872
TI  - [Surgical treatment of primary hyperparathyroidism].
AB  - OBJECTIVE: To investigate the causes of misdiagnosis and the surgical treatment
      of primary hyperparathyroidism (PHPT). METHODS: The clinical data of 26 patients
      with PHPT from July 2008 to January 2013 in The Affiliated Hospital of Chengde
      Medical College and The Fourth Hospital of Hebei Medical University were
      retrospectively analyzed, including preoperative diagnosis and operative method.
      The level of serum calciumion and serum parathyroid hormone (PTH),
      Ultrasonography, CT, (99)mTc-methoxy isobutylis onitrile ((99)mTc-MIBI) were used
      in the diagnosis before operation. All patients accepted surgical treatment after
      the level of serum calciumion decreased to normal. RESULTS: The level of PTH was
      examined 10 min after resection, which declined more than 50%. After pathological
      examination, 23 cases were diagnosed as parathyroid adenoma, 2 cases were
      parathyroid hyperplasia, and 1 case was parathyroid carcinoma. The level of serum
      calciumion and serum parathyroid hormone were returned to the normal level after
      operation. All patients recovered with no postoperative complication.Followed up
      lasted from 6 months to 5 years, no case recurred.Sixteen cases with symptoms
      experienced significant improvement in signs, including 10 cases with clinical
      symptoms completely disappeared. CONCLUSIONS: The test of serum calciumion and
      serum PTH, Ultrasonography, CT, (99)mTc-MIBI are helpful to reduce the
      misdiagnose rate of primary hyperparathyroidism before operation. The examination
      of serum parathyroid hormone in operation is helpful to reduce the operation
      range and time.

PMID- 24330873
TI  - [Thyroid lymphography:a new clinical approach for protecting parathyroid in
      surgery].
AB  - OBJECTIVE: To research the role of lymph tracers to protect parathyroid in
      surgery for papillary thyroid carcinoma. METHODS: Patients with papillary thyroid
      carcinoma who met selected criteria were enrolled in this study. Patients were
      divided into carbon nanoparticle group, methylene blue group, and conventional
      surgery group. RESULTS: No significant complication occurred in the patients of
      carbon nanoparticle and methylene blue groups. In carbon nanoparticle group,
      methylene blue group and conventional surgery group, the mean numbers of
      parathyroid glands detected during surgery were 3.1 +/- 0.3, 2.9 +/- 0.4 and 2.3
      +/- 0.3 (F = 3.78, P < 0.01) , the rates that parathyroid was cut mistakenly were
      1.37% (2/146) , 2.62% (2/97) and 7.14% (6/84) respectively (chi(2) = 17.372, P <
      0.05) ; and the incidence of postoperative hypocalcemia were 10.4% (5/48) , 9.1%
      (3/33) and 17.5% (7/40,chi(2) = 0.671, P = 0.037) . CONCLUSION: Thyroid
      lymphography technique is helpful to protect from the injury to the parathyroid
      glands in surgery.

PMID- 24330874
TI  - [Differential diagnostic value of contrast-enhanced ultrasound in calcified
      thyroid nodules].
AB  - OBJECTIVE: To evaluate the diagnostic value of contrast-enhanced ultrasound(CEUS)
      in calcified thyroid nodules. METHODS: A total of 179 cases with calcified
      thyroid nodules between February 2009 and September 2012 underwent CEUS by
      injection of microbubbles via superficial vein was included in the study.
      Pathological diagnosis as a gold standard, the sensitivity, specificity, positive
      predictive, negative predictive and diagnostic coincidence rate of CEUS were
      evaluated. RESULTS: Among 110 cases of benign nodules, 62 cases were nodular
      goiter (46 cases with macrocalcification and 16 cases with microcalcification);
      29 cases were adenoma (28 cases with macrocalcification and 1 case with
      microcalcification); 17 cases were Hashimoto's thyroid (13 cases with
      macrocalcification and 4 cases with microcalcification); and 2 cases were
      granuloma with microcalcification. Among 69 cases of malignant nodules (t =
      14.33, P < 0.05), 68 cases were papillary carcinoma (60 cases with
      microcalcification and 8 cases with macrocalcification), and 1 case of medullary
      carcinoma with microcalcification. Malignant nodules mainly showed weak
      inhomogeneous enhancement, with the mean; peak intensity (51.38 +/- 14.33)dB that
      was lower than that (92.37 +/- 33.36)dB in benign nodules, and benign nodules
      showed isoenhancement or hyperenhancement, with significant differences compared
      to malignant nodules (t = 14.33, P < 0.05) , however, there were significant
      differences in the enhanced time and the time to peak between benign and
      malignant nodules. The sensitivity, specificity, positive predictive, negative
      predictive and diagnostic coincidence rate of CEUS for the diagnoses of thyroid
      nodules were 92.75%, 90.91%, 86.49%, 95.24% and 91.62%, respectively. CONCLUSION:
      CEUS has high value in differential diagnosis of benign and malignant calcified
      thyroid nodules.

PMID- 24330875
TI  - [Application of ultrasound-guided drawing location of thyroid micronodule].
AB  - OBJECTIVE: To evaluate the application value of preoperative ultrasound-guided
      drawing for locating thyroid micronodule in surgery. METHODS: A total of 88
      patients (with 137 thyroid micronodules) who underwent thyroid surgery was
      included in the prospective study. Preoperative thyroid ultrasound was conducted
      in all patients. Select criteria: the maximum diameter of nodule <= 1 cm. All
      patients were randomly divided into two groups: 46 patients (68 micronoduls) in
      experimental group with ultrasound-guided drawing location of thyroid micronodule
      and 42 patients (69 micronoduls) in control group without ultrasound-guided
      drawing location of thyroid micronodule. RESULTS: All thyroid micronodules of
      experimental group were found quickly and accurately in surgery, and 4
      micronodules in 4 patients of control group were not found in surgery. US
      examinations 3 months after surgery showed that all micronodules in experimental
      group were completely removed and 4 micronodules in control group retained.
      CONCLUSION: Ultrasound-guided drawing is a useful technique for locating and
      searching accurately thyroid micronodule in surgery.

PMID- 24330876
TI  - [Clinical application of Sniffin' Sticks olfactory psychophysical measurements].
AB  - OBJECTIVES: To establish the normal value of Sniffin' Sticks test in Chinese
      population and to explore it's clinical application in China. METHODS: One
      hundred and five healthy volunteers were choosen from the department of physical
      examination of Beijing Tongren Hospital between 2007 and 2013. Another 165
      patients complained of abnormal olfactory function were obtained from the
      outpatient clinic of the department of otorhinolaryngology head and neck surgery
      in the same period and were divided into two groups: 92 in hyposmia and 73 in
      functional anosmia group. The 270 subjects were divided into 3 subgroups:younger
      group ( <35 years of age), middle-age group (35-55 years of age) and older group
      ( > 55 years of age). The olfactory functions were examined with Sniffin' Sticks
      test and T & T test, respectively. All analyses were performed using SPSS 12.0
      software. RESULTS: For the normal value of Sniffin' Sticks test, TDI score was >
      30.12 for younger group, > 27.37 for middle-age group and > 20.43 for older
      group; the mean TDI score was 32.12 +/- 3.95 for healthy group, 17.52 +/- 10.37
      for hyposmia and 3.56 +/- 3.49 for functional anosmia group; the differences in
      TDI score, olfactory threshold, discrimination threshold and identification
      threshold between healthy group and olfactory dysfunction group with different
      ages had statistical significance (Younger group: FTDI = 125.136, P = 0.000; FT =
      49.454, P = 0.000;FD = 89.037, P = 0.000; FI = 39.888, P = 0.000; Middle-age
      group: FTDI = 190.240, P = 0.000; FT = 128.374, P = 0.000;FD = 174.122, P =
      0.000;FI = 178.945, P = 0.000;Older group: FTDI = 72.992, P = 0.000; FT = 26.599,
      P = 0.000; FD = 77.119, P = 0.000; FI = 88.107, P = 0.000, respectively) . The
      mean T & T value was -1.00 +/- 0.98 for healthy group, 2.27 +/- 2.01 for hyposmia
      and 5.89 +/- 0.14 for functional anosmia group. T & T score between healthy group
      and olfactory dysfunction group with different ages had statistical significance
      (Fyounger = 158.144, P = 0.000; Fmiddle-age = 247.695, P = 0.000; Folder =
      70.579, P = 0.000, respectively). TDI score of the Sniffin' Sticks test result
      was correlated with T & T value (r = -0.927, P < 0.01); T & T threshold was
      correlated with the olfactory threshold, discrimination threshold and
      identification threshold of Sniffin' Sticks test (rT = -0.846, P < 0.01, rD = 
      0.908 P < 0.01, rI = -0.864, P < 0.01, respectively). CONCLUSIONS: Sniffin'
      Sticks test and T & T olfactometry are able to differentiate normosmia from
      hyposmia and anosmia with high reliability and consistency in test
      results.Sniffin' Sticks test can assess subject's olfactory function status more
      thoroughly and is suitable for application in Chinese population.

PMID- 24330877
TI  - [Pathologic changes of the palatopharyngeal muscles in adult patients with
      obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To investigate the pathology of palatopharyngeal muscle obtained from
      patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: The
      samples from both groups were studied under HE, nicotinamide adenine dinucleotide
      tetrazolium reductase (NADH- TR), modified Gomori trichrome (MGT) and adenosine
      triphosphatase (ATPase) staining. There were 36 cases of OSAHS who received
      uvulopalatopharyngoplasty in the experimental group (including 6 mild, 6 moderate
      and 24 severe cases). There were 6 patients with chronic tonsillitis but without
      OSAHS as matched control group. Both groups were diagnosed by PSG. RESULTS:
      Centralized located nuclei and obvious variability of the size of fiber types
      were observed in both groups. The occurrence rate of the former were 1/6 in
      control group and 52.8% (19/36) in OSAHS, while the rate of the latter were 4/6
      and 58.3% (21/36)respectively. A large number of fibers in both groups (control
      group 5/6, OSAHS group 28/36) presented an irregularly distributed staining for
      oxidative activity reaction in NADH stain.Endomysium connective tissue
      proliferation, a lobular or motheaten appearance, target-like fibers, ragged red
      fiber (RRF) and muscle necrosis were only observed in OSAHS group.While it was
      more common in serious OSAHS patients. Dominance of type 1 fibers were observed
      in matched control group in ATPase stain. Clusters of type 2 fibers or clusters
      of both type fibers were observed in OSAHS, especially more common in serious
      OSAHS. There was a predominance of the type 2 fibers in some OSAHS patients.
      CONCLUSIONS: The observation of HE and special muscular stain identified that
      palatopharyngeal muscle of OSAHS patients had pathological lesion. The
      pathological changes included muscular lesion and abnormal distribution of
      different fiber types, the rate of type 1 fiber which maintained the opening of
      upper air way decreased.

PMID- 24330878
TI  - [Harmonic scalpel versus conventional resection in thyroid surgery: a meta
      analysis on the safety outcomes].
AB  - OBJECTIVE: To compare the safety between harmonic scalpel and conventional
      resection in total or near total thyroidectomy with meta-analysis. METHODS: The
      prospective randomized controlled studies were searched for in electronic
      databases (MEDLINE, EMBASE, Cochrane Library). Meta analysis of acquired data was
      performed through the use of RevMan 5.2 software. RESULTS: According to the
      inclusion criterion, 13 articles were enrolled which compared on the safety
      between harmonic scalpel and conventional resection in thyroid surgery. A total
      of 1620 patients with thyroid tumor were enrolled, including 802 patients in
      harmonic scalpel group and 818 patients in conventional resection group. Compared
      with conventional resection group, the harmonic scalpel group showed shorter time
      of surgery, the weighted mean difference (WMD) and their 95% confidence interval
      (95%CI) was -21.06[-25.65, -16.47], Z = 8.99, P < 0.00001; less intra-operative
      blood loss, WMD and 95%CI was -14.36[-20.67, -8.06], Z = 4.46, P < 0.00001; less
      post-operative drain output (WMD and 95%CI was -7.47[-11.35, -3.58], Z = 3.77, P
      = 0.0002); less hospitalization charges (WMD and 95%CI was -117.97[-131.65, 
      104.29], Z = 16.90, P < 0.00001). The incidence of postoperative transient
      recurrent laryngeal nerve dysfunction and transient hypocalcemia were similar in
      both groups. CONCLUSION: Using the harmonic scalpel in thyroid surgery was as
      safe as that of the conventional technique with the advantage of shorter time of
      surgery, less intraoperative blood loss and less postoperative drain output.

PMID- 24330879
TI  - [Effect of nasal cavity expansion surgery on chronic nasal obstructive diseases
      on the blood supply of the cerebral arterial system].
AB  - OBJECTIVE: To investigate the effect of nasal cavity expansion surgery on the
      abnormal blood supply of the cerebral arterial system. METHODS: Fifty-nine
      inpatients with abnormal blood supply of cerebral arterial system confirmed by
      transcranial doppler (TCD) and chronic nasal obstructive diseases were included
      in this study. All patients accepted nasal cavity expansion surgery and were
      followed-up with TCD every month after operation until TCD became normal, or up
      to seven months even if the TCD was still abnormal. SPSS 17.0 software was used
      to analyze the data. RESULTS: In all 59 patients, there were 164 TCD-abnormal
      cerebral arteries. Among them, 37 patients(62.71%) with abnormal TCD arteries
      became normal within 1 to 7 months after operation, 8 patients (13.56 %) got
      better, but 14 patients (23.73 %) did not improve. CONCLUSIONS: Abnormal blood
      flow of some cerebral arteries was possibly induced by increasing the activation
      of sympathetic nervous system around the vertebral arterial system, caused by
      chronic nasal obstruction. Nasal dilatancy surgery can improve the blood
      supplement of the cerebral arterial system.

PMID- 24330881
TI  - [Clinical investigation on blood supply in whole nasal reconstruction using
      median forehead island flap and median forehead pedicled].

PMID- 24330880
TI  - [Influence on cell proliferation by small interfering RNA of Cyclin Y expression
      in laryngeal cancer cells].
AB  - OBJECTIVE: The effects of lentivirus-mediated suppression of Cyclin Y (CCNY)
      expression on the proliferation of laryngeal cancer cells were investigated in
      vitro. METHODS: The lentivirus vectors containing a small hairpin RNA (shRNA) to
      target CCNY were constructed.Hep-2 cells were divided into the following two
      experimental groups:the negative control group (control lentivirus infected
      cells) and CCNY knockdown group (CCNY shRNA-expressing lentivirus infected
      cells). After Hep-2 cells were infected, Real-time PCR was used to measure CCNY
      expression. The influence of CCNY on the proliferation of laryngeal cancer cells
      were assessed using MTT and colony formation experiments.Each experiment was
      performed in triplicate and repeated three times. RESULTS: Lentiviruses
      expressing shRNA against CCNY were constructed and Hep-2 cells were infected with
      above mentioned lentivirus at MOI (Multiplicity of infection) of 120.Real-time
      PCR analysis showed that the mRNA expression of CCNY in Hep-2 cells in the
      knockdown group was significantly decreased (P < 0.05); the mRNA level of CCNY
      was 75.3% lower in the si-CCNY group than in the si-CTRL group. After 5 days of
      lentiviral infection, the cell viability was significantly lower in cells
      infected with the CCNY-shRNA lentivirus compared to cells infected with the
      control lentivirus following a 6-day incubation. The colony number was decreased
      by 60% in Hep-2 cells infected with the CCNY-shRNA-lentivirus infected cells
      following a 10-day incubation. CONCLUSIONS: The results suggested that lentivirus
      mediated downregulation of CCNY expression decreased the proliferation and growth
      potency of laryngeal cancer cells.Lentiviruses delivering shRNA against CCNY may
      be a promising tool for laryngeal cancer therapy.

PMID- 24330882
TI  - [A case report of Kaino-syndrome after a large sphenoid sinus cyst operation].

PMID- 24330883
TI  - [Controlling therapy with propranolol for infants with parotid gland
      hemangiomas].

PMID- 24330884
TI  - [Primary tuberculosis of unilateral vocal cord: two case reports].

PMID- 24330885
TI  - [Analysis of the misdiagnosed patients with laryngeal tuberculosis: report of
      three cases].

PMID- 24330886
TI  - [Diagnosis and treatment of three sporadic patients with Crouzon syndrome].

PMID- 24330887
TI  - [Diagnosis and treatment of parathyroid space-occupying lesions progress].

PMID- 24330888
TI  - [Status of dragnosis and treatment in thyroid nodular disease].

PMID- 24330889
TI  - [Objective analysis of facial motion based on the optics measurement].

PMID- 24330890
TI  - [Functional preservation and restoration of recurrent laryngeal nerve and
      parathyriod in throidectomy].

PMID- 24330891
TI  - Posttraumatic stress disorder and cognitive function: findings from the mind your
      heart study.
AB  - OBJECTIVE: Prior studies have found that the patients with posttraumatic stress
      disorder (PTSD) have poorer performance on cognitive tests than patients without
      PTSD, but the underlying mechanisms remain unknown. We examined the association
      between PTSD and cognitive function in a large cohort and evaluated the role of
      potential biological and behavioral mediators. METHOD: A cohort of 535 adult
      outpatients (<= 65 years) without dementia, stroke, or other neurologic disorders
      was recruited from 2 Veterans Affairs medical centers between February 2008 and
      June 2010. PTSD was assessed with the Clinician Administered PTSD Scale (CAPS)
      using DSM-IV-TR criteria. Cognitive function tests included processing speed,
      Trails A and B, letter fluency, category fluency, and verbal learning and
      recognition. Linear regression was used to evaluate the association between PTSD
      and cognitive function test scores and to assess potential mediators of the
      association. RESULTS: For our analyses of PTSD and cognitive function, we
      combined 178 participants who met criteria for full PTSD and 18 who met criteria
      for partial PTSD and had a CAPS score > 40. After adjusting for demographics,
      these participants with PTSD scored significantly worse on processing speed (0.30
      standard deviations [SDs], P <= .001), category fluency (0.23 SDs, P = .01),
      verbal learning (0.30 SDs, P = .001), and verbal recognition (0.18 SDs, P = .048)
      than those without PTSD. These associations were largely accounted for by health
      behaviors, vascular risk factors, and depression. CONCLUSIONS: In this cohort of
      veterans under age 65 years without known neurologic disease, patients with
      versus without PTSD had significantly poorer performance in several domains of
      cognitive function, particularly in tests involving processing speed, executive
      function, and learning. These cognitive deficits were largely explained by
      modifiable risk factors. Interventions targeted at these risk factors might
      minimize the impact of PTSD on cognitive decline and dementia risk as patients
      age.

PMID- 24330892
TI  - Differentiating ictal panic with low-grade temporal lobe tumors from psychogenic
      panic attacks.
AB  - OBJECTIVE: Indolent low-grade temporal lobe tumors may present with ictal panic
      that may be difficult to differentiate from psychogenic panic attacks. The
      current study aims to demonstrate the differences between the two disorders and
      help physicians generate a diagnostic paradigm. METHOD: This was a retrospective
      study of 43 patients who underwent a temporal lobectomy between 1981 and 2008 for
      the treatment of intractable temporal lobe epilepsy secondary to low-grade
      neoplasms at Rush University Medical Center. A total of 10 patients in this group
      presented with ictal panic who were previously being treated for psychogenic
      panic attacks. Medical records were reviewed for age at seizure onset, duration
      of symptoms, lateralization of the epileptogenic zone, pathological diagnosis,
      and postsurgical seizure outcome according to the modified Engel classification.
      RESULTS: Neuropathologic findings of the 10 tumors were pleomorphic
      xanthoastrocytoma, ganglioglioma, oligodendroglioma, and dysembryoplastic
      neuroepithelial. The mean age of the patients undergoing surgery was 28 years
      (range, 15-49). The mean duration of panic symptoms prior to surgery was 9.8
      years (range, 3-23). All patients had unprovoked ictal panic. None had symptoms
      suggestive of a brain tumor, such as signs of increased intracranial pressure or
      any focal neurologic deficit. In 5 of the patients, other symptoms associated
      with the ictal panic, including unusual sounds, nausea, automatism, uprising
      gastric sensation, and deja vu were identified. Gross total resection of the
      lesion resulted in improved seizure outcome in all patients undergoing surgery.
      Patient follow-up was, on average, 7.4 years (range, 2-14) from time of surgery.
      CONCLUSIONS: Although similar, ictal panic from epilepsy and classic panic
      attacks are clinically distinguishable entities with different modalities of
      treatment. A careful history may help differentiate patients with ictal panic
      from those with psychogenic panic attacks and determine for which patients to
      obtain neuroimaging studies.

PMID- 24330893
TI  - Randomized placebo-controlled adjunctive study of an extract of withania
      somnifera for cognitive dysfunction in bipolar disorder.
AB  - OBJECTIVE: Cognitive impairments contribute significantly to inadequate
      functional recovery following illness episodes in bipolar disorder, yet data on
      treatment interventions are sparse. We assessed the cognitive effects of a
      standardized extract of the medicinal herb Withania somnifera (WSE) in bipolar
      disorder. METHOD: Sixty euthymic subjects with DSM-IV bipolar disorder were
      enrolled in an 8-week, double-blind, placebo-controlled, randomized study of WSE
      (500 mg/d) as a procognitive agent added adjunctively to the medications being
      used as maintenance treatment for bipolar disorder. Study enrollment and data
      analyses were completed between December 2008 and September 2012. Cognitive
      testing at baseline and 8 weeks assessed primary efficacy outcomes.
      Psychopathology and adverse events were monitored at scheduled visits. RESULTS:
      Fifty-three patients completed the study (WSE, n = 24; placebo, n = 29), and the
      2 groups were matched in terms of demographic, illness, and treatment
      characteristics. Compared to placebo, WSE provided significant benefits for 3
      cognitive tasks: digit span backward (P = .035), Flanker neutral response time (P
      = .033), and the social cognition response rating of the Penn Emotional Acuity
      Test (P = .045). The size of the WSE treatment effect for digit span backward was
      in the medium range (Cohen d = 0.51; 95% CI, 0.25-0.77). None of the other
      cognitive tasks showed significant between-group differences. Mood and anxiety
      scale scores remained stable, and adverse events were minor. CONCLUSIONS:
      Although results are preliminary, WSE appears to improve auditory-verbal working
      memory (digit span backward), a measure of reaction time, and a measure of social
      cognition in bipolar disorder. Given the paucity of data for improving cognitive
      capacity in bipolar disorder, WSE offers promise, appears to have a benign side
      effects profile, and merits further study. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00761761.

PMID- 24330895
TI  - Introduction: Early career offerings.

PMID- 24330894
TI  - The prevalence and severity of depressive symptoms along the spectrum of unipolar
      depressive disorders: a post hoc analysis.
AB  - OBJECTIVE: To explore which symptoms are common in patients who experience a
      range of symptom severity that spans minor depression and major depressive
      disorder (MDD). METHOD: A post hoc analysis of subjects entering outpatient,
      pharmacologic treatment studies for minor depression or MDD who provided baseline
      data on the Inventory for Depressive Symptomatology-Clinician Rated (IDS-C) was
      performed in November 2000. The minor depression sample included 161 patients
      diagnosed according to the National Institute of Mental Health Diagnostic
      Interview Schedule, while the MDD subjects included 969 subjects diagnosed
      according to the Structured Clinical Interview for DSM-III-R. Descriptive
      statistics were calculated for the total IDS-C score and for each item-rating
      score for both groups. The percentages of patients within the low, medium, and
      high severity groups of minor depression and MDD endorsing each IDS-C item were
      calculated and used to identify specific patterns of prevalence across the 6
      groups: symptoms with high prevalence in all groups (core symptoms), those with
      increasing prevalence across groups (continuum symptoms), and those that become
      prominent only at a certain threshold of illness severity. RESULTS: The mean (SD)
      IDS-C score was 21.18 (5.37) for minor depression patients, while it was 37.14
      (7.27) for the MDD patients (P = .0001). Ten items pertaining mostly to mood
      state and cognition were identified as "core" symptoms of depression based on
      their high prevalence in all groups. Fourteen items consisting mostly of
      neurovegetative and somatic symptoms were identified as "continuum" symptoms
      based on their general pattern of increasing prevalence across the 6 severity
      groups. Four "threshold" symptoms, including suicidal ideation, psychomotor
      slowing, gastrointestinal symptoms, and panic/phobic symptoms, were prevalent in
      only the most severely depressed groups. CONCLUSIONS: The presence of core,
      continuum, and threshold depressive symptoms indicates central features of both
      minor depression and MDD as well as symptoms that increase or emerge with
      depressive illness severity. Some of the core symptoms of minor depression and
      MDD are not included in DSM depressive criteria or traditional assessment rating
      scales.

PMID- 24330896
TI  - Probability and predictors of first treatment contact for anxiety disorders in
      the United States: analysis of data from the National Epidemiologic Survey on
      Alcohol and Related Conditions (NESARC).
AB  - BACKGROUND: Despite the high prevalence of anxiety disorders and the demonstrated
      efficacy of their treatment, most individuals with anxiety disorders never
      utilize mental health services. OBJECTIVE: To identify predictors of treatment
      seeking for DSM-IV anxiety disorders from a range of sociodemographic factors and
      comorbid mental disorders. DESIGN: Survival analysis with time-varying covariates
      was performed using data from the National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC). SETTING: Face-to-face interviews conducted in the
      United States. PARTICIPANTS: 34,653 respondents, aged 18 years and older, from
      the 2004-2005 Wave 2 NESARC. MAIN OUTCOME MEASURE: The cumulative probability of
      treatment-seeking (assessed by the Alcohol Use Disorder and Associated
      Disabilities Interview Schedule-DSM-IV version, Wave 2 version) across the
      anxiety disorders in 1 year, 10 years, and lifetime and the median delay to the
      first treatment contact. RESULTS: Most individuals with panic disorder sought
      treatment within the same year of disorder onset, whereas the median delays to
      first treatment contact for generalized anxiety disorder, specific phobia, and
      social anxiety disorder were 1 year, 13 years, and 16 years, respectively.
      Several personality disorders and earlier age at anxiety disorder onset decreased
      the probability of treatment contact. By contrast, younger cohort membership, a
      recent change in marital status, treatment for a psychiatric disorder other than
      substance use disorder, and comorbid anxiety disorders increased the lifetime
      probability of treatment contact. CONCLUSIONS: Treatment-seeking rates for most
      anxiety disorders are low, are associated with long delays, and sometimes are
      hindered by co-occurrence of other psychopathology. These patterns highlight the
      complex interplay of personal characteristics, individual psychopathology, and
      social variables in the treatment-seeking process.

PMID- 24330897
TI  - Modafinil augmentation therapy in unipolar and bipolar depression: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Current pharmacologic treatments for a depressive episode in unipolar
      major depressive disorder (MDD) and bipolar depression are limited by low rates
      of remission. Residual symptoms include a persistent low mood and neurovegetative
      symptoms such as fatigue. The objective of this study was to examine the efficacy
      and tolerability of augmentation of first-line therapies with the novel stimulant
      like agent modafinil in MDD and bipolar depression. DATA SOURCES: MEDLINE/PubMed,
      PsycINFO, 1980-April 2013 were searched using the following terms: (modafinil or
      armodafinil) and (depressi* or depressed or major depressive disorder or major
      depression or unipolar or bipolar or dysthymi*). Inclusion criteria were as
      follows: randomized controlled trial (RCT) design, sample comprising adult
      patients (18-65 years) with unipolar or bipolar depression, diagnosis according
      to DSM-IV, ICD-10, or other well-recognized criteria, modafinil or armodafinil
      given as augmentation therapy in at least 1 arm of the trial, and publication in
      English in a peer-reviewed journal. STUDY SELECTION: Double-blind, randomized,
      placebo-controlled clinical trials of adjunctive treatment with modafinil or
      armodafinil of standard treatment for depressive episodes in MDD and bipolar
      depression were selected. DATA EXTRACTION: Two independent appraisers assessed
      the eligibility of the trials. A random-effects meta-analysis with DerSimonian
      Laird method was used. Moderator effects were evaluated by meta-regression.
      RESULTS: Data from 6 RCTs, with a total of 910 patients with MDD or bipolar
      depression, consisting of 4 MDD RCTs (n = 568) and 2 bipolar depression RCTs (n =
      342) were analyzed. The meta-analysis revealed significant effects of modafinil
      on improvements in overall depression scores (point estimate = -0.35; 95% CI, 
      0.61 to -0.10) and remission rates (odds ratio = 1.61; 95% CI, 1.04 to 2.49). The
      treatment effects were evident in both MDD and bipolar depression, with no
      difference between disorders. Modafinil showed a significant positive effect on
      fatigue symptoms (95% CI, -0.42 to -0.05). The adverse events were no different
      from placebo. CONCLUSIONS: Modafinil is an effective augmentation strategy for
      acute depressive episodes, including for symptoms of fatigue, in both unipolar
      and bipolar disorders.

PMID- 24330898
TI  - Switching antipsychotic medications to reduce adverse event burden in
      schizophrenia: establishing evidence-based practice.
AB  - The purpose of this project was to provide evidence-based guidance concerning
      when and how it is appropriate to undertake elective changes in antipsychotic
      medications in order to reduce adverse effects, with a focus on those adverse
      effects associated with increased long-term health risks. This project extends
      the results of the National Institute of Mental Health-funded 2009 Schizophrenia
      Patient Outcomes Research Team (PORT) psychopharmacologic treatment
      recommendations. The authors reviewed the literature on switching antipsychotics,
      focusing on randomized controlled trials published since the 2009 Schizophrenia
      PORT. The studies reviewed support a recommendation that an elective switch from
      higher to lower metabolic risk antipsychotics can produce weight and lipid
      benefits without significant risk of clinical deterioration. Evidence also
      suggests that certain antipsychotic switches may improve other adverse effects,
      including extrapyramidal symptoms and prolactin elevation. In deciding to make an
      elective change of antipsychotic medication, it is important to conduct a careful
      risk/benefit assessment with the patient. Before initiating a switch, patients
      should be educated about what to expect during the process. Studies also support
      gradual discontinuation of the current medication in order to minimize problems
      early in the switching process. 

PMID- 24330899
TI  - The role of vitamin D in depression: from a curious idea to a therapeutic option.

PMID- 24330900
TI  - Biased reporting of results in patients at ultra-high risk of psychosis.

PMID- 24330901
TI  - Dr McGorry and colleagues reply.

PMID- 24330902
TI  - Long-term effects of ADHD medication on adult height: results from the NESARC.

PMID- 24330903
TI  - Efficacy and cognitive side effects after brief pulse and ultrabrief pulse right
      unilateral electroconvulsive therapy for major depression: a randomized, double
      blind, controlled study.
AB  - OBJECTIVE: To compare the efficacy and cognitive side effects of high-dose
      unilateral brief pulse electroconvulsive therapy (ECT) with those of high-dose
      unilateral ultrabrief pulse ECT in the treatment of major depression. METHOD:
      From April 2007 until March 2011, we conducted a prospective, double-blind,
      randomized multicenter trial in 3 tertiary psychiatric hospitals. All patients
      with a depressive disorder according to DSM-IV criteria were eligible. Depression
      severity was assessed with the Montgomery-Asberg Depression Rating Scale; primary
      efficacy outcomes were response, defined as a score decrease >= 60% from
      baseline, and remission, defined as a score < 10 at 2 consecutive weekly
      assessments. Total scores on the Autobiographical Memory Interview and Amsterdam
      Media Questionnaire were the primary outcome measures for retrograde amnesia.
      Other cognitive domains included category fluency (semantic memory) and letter
      fluency (lexical memory). Patients received twice-weekly unilateral brief pulse
      (1.0 millisecond) or ultrabrief pulse (0.3-0.4 millisecond) ECT 8 times seizure
      threshold until remission, for a maximum of 6 weeks. RESULTS: Of the 116
      patients, 75% (n = 87) completed the study. Among completers, 68.4% (26/58) of
      those in the brief pulse group achieved remission versus 49.0% (24/49) of those
      in the ultrabrief pulse group (P = .019), and the brief pulse group needed fewer
      treatment sessions to achieve remission: mean (SD) of 7.1 (2.6) versus 9.2 (2.3)
      sessions (P = .008). No significant group differences were found in the
      evaluation of the cognitive assessments. CONCLUSIONS: The efficacy and speed of
      remission seen with high-dose brief pulse right unilateral ECT twice weekly were
      superior to those seen with high-dose ultrabrief pulse right unilateral ECT, with
      equal cognitive side effects as defined by retrograde amnesia, semantic memory,
      and lexical memory. TRIAL REGISTRATION: Netherlands National Trial Register
      number: NTR1304.

PMID- 24330904
TI  - Effects of 1-year treatment with highly purified omega-3 fatty acids on
      depression after myocardial infarction: results from the OMEGA trial.
AB  - OBJECTIVE: The effects of supplementation of the omega-3 fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on prevalence and
      severity of depression were evaluated in patients after a myocardial infarction.
      METHOD: A cross-sectional evaluation (posttest-only design) within the
      prospective, randomized, controlled, multicenter OMEGA trial was performed in
      patients after myocardial infarction at 12 months' follow-up (N = 2,081; age,
      mean = 64 years; men, 76.7%; women, 21.8%) from April 2005 to June 2007. Patients
      received supplementation with ethyl esters 90 (460-mg EPA and 380-mg DHA) or
      placebo for 12 months. Depression was assessed with the Beck Depression Inventory
      II (BDI-II); a BDI-II cutoff score of >= 14 was used as diagnosis of depression.
      RESULTS: When the total population was evaluated, no effects of EPA/DHA
      supplementation on depressive symptoms according to BDI-II score (mean [SD])
      could be demonstrated: EPA/DHA (n = 1,046), 7.1 (6.9); placebo (n = 1,035), 7.1
      (7.0); P = .7. The post hoc analyses of depressed patients with and without
      antidepressants revealed a tendency toward an antidepressant effect in patients
      with EPA/DHA supplementation as monotherapy: EPA/DHA (n = 125), 19.4 (5.8);
      placebo (n = 113), 19.9 (5.1); P = .07. However, in depressed patients with
      EPA/DHA supplementation as adjunctive to conventional antidepressants, a
      clinically relevant antidepressant effect was demonstrated: EPA/DHA (n = 33),
      20.9 (7.1); placebo (n = 29), 24.9 (8.5); P < .05. CONCLUSIONS: EPA/DHA
      supplementation in the total sample of patients after myocardial infarction had
      no effect on depressive symptoms. The clinically relevant antidepressant effect
      in the subgroup of depressed patients with EPA/DHA supplementation as adjunctive
      to conventional antidepressants that was revealed in the post hoc analysis might
      provide a basis for a controlled, prospective trial of omega-3 augmentation of
      antidepressants in patients after myocardial infarction. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00251134.

PMID- 24330905
TI  - Symptomatic remission and cognitive impairment in first-episode schizophrenia: a
      prospective 3-year follow-up study.
AB  - OBJECTIVE: Cognitive impairment is a core feature of schizophrenia, but its
      relationship with symptomatic remission has been understudied. This study aimed
      to examine the concurrent and longitudinal relationships between cognitive
      functioning and symptomatic remission in first-episode schizophrenia. METHOD: The
      sample comprised 92 Chinese patients, aged 18 to 55 years, who presented with
      first-episode DSM-IV schizophrenia spectrum disorder and were recruited from both
      outpatient and inpatient psychiatric units covering a defined catchment area in
      Hong Kong. The study commenced in September 1997 and ended in March 2005.
      Psychopathological evaluation was conducted using the Positive and Negative
      Syndrome Scale (PANSS) and the High Royds Evaluation of Negativity (HEN) scale at
      intake, after clinical stabilization of the first psychotic episode, and at 12,
      24, and 36 months. Cognitive functions were measured at clinical stabilization
      and at 12, 24, and 36 months. Sustained symptomatic remission was operationally
      defined as fulfillment of mild severity ratings or less at 24 and 36 months on
      selected PANSS items for positive symptoms and on the basis of Andreasen's
      criteria and HEN subscales for negative symptoms. RESULTS: At the end of the 3
      year follow-up, 44.6% of patients achieved sustained symptomatic remission.
      Remitted patients had significantly better concurrent verbal memory (F = 4.6, P <
      .01) and functional (t = -2.4, P < .05) and vocational (t = 4.8, P < .01)
      outcomes at 36 months than nonremitted counterparts. Sustained remission
      attainment was associated with better premorbid adjustment (t = -3.1, P < .01),
      better baseline occupational status (chi(2) = 4.7, P < .05), better 1-year verbal
      memory (F = 6.4, P < .01), and fewer 1-year positive (t = -2.9, P < .01) and
      negative (t = -4.7, P < .01) symptoms. Logistic regression indicated that verbal
      memory impairment, premorbid functioning, and negative symptom severity
      independently predicted remission status (Nagelkerke R(2) = 0.425, P < .0001).
      CONCLUSIONS: Our findings provide supportive evidence that verbal memory
      impairment might be specifically related to attainment of sustained remission in
      the early stage of schizophrenia.

PMID- 24330906
TI  - Transcranial direct current stimulation for refractory auditory hallucinations in
      schizophrenia.
AB  - Some patients with schizophrenia may suffer from continuous or severe auditory
      hallucinations that are refractory to antipsychotic drugs, including clozapine.
      Such patients may benefit from a short trial of once- to twice-daily transcranial
      direct current stimulation (tDCS) with the cathode placed over the left
      temporoparietal cortex and the anode over the left dorsolateral prefrontal
      cortex; negative, cognitive, and other symptoms, if present, may also improve. At
      present, the case for tDCS treatment of refractory auditory hallucinations rests
      on 1 well-conducted randomized, sham tDCS-controlled trial and several carefully
      documented and instructive case reports. Benefits with up to 3 years of
      maintenance tDCS have also been described. In patients with refractory auditory
      hallucinations, tDCS has been delivered at 1- to 3-mA current intensity during 20
      30 minutes in once- to twice-daily sessions for up to 3 years with no apparent
      adverse effects. Transcranial direct current stimulation therefore appears to be
      a promising noninvasive brain stimulation technique for patients with
      antipsychotic-refractory auditory hallucinations. 

PMID- 24330909
TI  - Nutrient deposition partitioning and priorities between body compartments in two
      size classes of rainbow trout in response to feed restriction.
AB  - Adaptations in growth dynamics in fish, i.e. how fish prioritise tissue accretion
      between organs, remains poorly understood. In the present study, we investigated
      the effects of graded feed restriction levels on nutrient deposition in 1.3 g
      fingerlings and 70 g juveniles. At the whole-body level, highly restricted
      juveniles strove to maintain body protein while mobilising lipid reserves and
      compensating for mass loss by increasing water content. In contrast, fingerlings
      maintained body water and energy contents. Additionally, we investigated
      deposition patterns in four body compartments (red and white axial muscles,
      viscera and rest of the carcass) in juveniles and changes in the cellularity of
      the white and red muscles in fingerlings. We provide evidence of priorities in
      growth and nutrient deposition in body compartments in response to low feeding
      levels. In juveniles, feed intake (FI) primarily affected the white muscle, while
      the red muscle and the viscera appeared to be preserved. Specific proteins (45
      and 173 kDa) were preferentially deposited in the white muscle, while others (22
      and 32 kDa) were preferentially mobilised. In fingerlings' muscle anterior to the
      anus, the cross-sectional surface areas increased with increasing FI in a
      logarithmic fashion in the white muscle, and in linear fashion in the red muscle.
      The maximum diameter of white fibres decreased linearly with fish length, while
      that of red fibres remained stable. This suggests an adaptation mechanism by
      decreasing white muscle hyperplasia in favour of hypertrophy when feed is
      restricted. Overall, these results indicate some mechanisms by which fish cope
      with low food availability. Our findings also suggest different adaptation
      strategies employed by fish of different body weights.

PMID- 24330911
TI  - Cataract surgery in glaucoma patients: how much benefit?

PMID- 24330912
TI  - The investment in cataract surgery yields healthy rewards.

PMID- 24330913
TI  - Intravitreal bevacizumab for symptomatic retinal arterial macroaneurysm.

PMID- 24330914
TI  - Reply: To PMID 23385203.

PMID- 24330915
TI  - Clinical characteristics of reticular pseudodrusen in Korean patients.

PMID- 24330916
TI  - Reply: To PMID 21996310.

PMID- 24330918
TI  - Baseline heartbeat perception accuracy and short-term outcome of brief cognitive
      behaviour therapy for panic disorder with agoraphobia.
AB  - BACKGROUND: Increased heartbeat perception accuracy (HBP-accuracy) may contribute
      to the pathogenesis of Panic Disorder (PD) without or with Agoraphobia (PDA).
      Extant research suggests that HBP-accuracy is a rather stable individual
      characteristic, moreover predictive of worse long-term outcome in PD/PDA
      patients. However, it remains still unexplored whether HBP-accuracy adversely
      affects patients' short-term outcome after structured cognitive behaviour therapy
      (CBT) for PD/PDA. AIM: To explore the potential association between HBP-accuracy
      and the short-term outcome of a structured brief-CBT for the acute treatment of
      PDA. METHOD: We assessed baseline HBP-accuracy using the "mental tracking"
      paradigm in 25 consecutive medication-free, CBT-naive PDA patients. Patients then
      underwent a structured, protocol-based, 8-session CBT by the same therapist.
      Outcome measures included the number of panic attacks during the past week, the
      Agoraphobic Cognitions Questionnaire (ACQ), and the Mobility Inventory-Alone
      subscale (MI-alone). RESULTS: No association emerged between baseline HBP
      accuracy and posttreatment changes concerning number of panic attacks. Moreover,
      higher baseline HBP-accuracy was associated with significantly larger reductions
      in the scores of the ACQ and the MI-alone scales. CONCLUSION: Our results suggest
      that in PDA patients undergoing structured brief-CBT for the acute treatment of
      their symptoms, higher baseline HBP-accuracy is not associated with worse short
      term outcome concerning panic attacks. Furthermore, higher baseline HBP-accuracy
      may be associated with enhanced therapeutic gains in agoraphobic cognitions and
      behaviours.

PMID- 24330917
TI  - Incidence and clinical presentation of acute otitis media in children aged <6
      years in European medical practices.
AB  - We conducted an epidemiological, observational cohort study to determine the
      incidence and complications of acute otitis media (AOM) in children aged <6
      years. Data on physician-diagnosed AOM were collected from retrospective review
      of medical charts for the year preceding enrolment and then prospectively in the
      year following enrolment. The study included 5776 children in Germany, Italy,
      Spain, Sweden, and the UK. AOM incidence was 256/1000 person-years [95%
      confidence interval (CI) 243-270] in the prospective study period. Incidence was
      lowest in Italy (195, 95% CI 171-222) and highest in Spain (328, 95% CI 296-363).
      Complications were documented in <1% of episodes. Spontaneous tympanic membrane
      perforation was documented in 7% of episodes. Both retrospective and prospective
      study results were similar and show the high incidence during childhood in these
      five European countries. Differences by country may reflect true differences and
      differences in social structure and diagnostic procedures.

PMID- 24330919
TI  - A blueprint for practice: pediatric nursing: scope and standards of practice.

PMID- 24330920
TI  - Violence prevention: a nursing issue.

PMID- 24330921
TI  - Common opportunistic infections and their CD4 cell correlates among HIV-infected
      patients attending at antiretroviral therapy clinic of Gondar University
      Hospital, Northwest Ethiopia.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) pandemic is among the greatest
      health crises ever faced by humanity. Morbidity and mortality in HIV disease is
      due to immunosuppression leading to life-threatening opportunistic infections
      (OIs) during the natural course of the disease. This study was aimed to assess
      the prevalence and CD4 correlates of OIs among adult HIV-infected patients
      attending at Gondar University Hospital. METHODS: Cross sectional study was
      conducted on 360 adult HIV-infected patients attending antiretroviral therapy
      clinic from February 2012-April 2012. Patients' OI status was determined through
      clinical diagnosis and laboratory investigations. CD4 count was determined using
      flow cytometry technique. Sociodemographic and clinical data were obtained from
      interview and patients' medical records. Bivariate and multivariate logistic
      regression analysis was done using SPSS version 16 statistical soft ware and odds
      ratio was used as the measure of association. P-value less than 0.05 was
      considered statistically significant for all tests. RESULTS: In this study, 360
      HIV-infected patients were included; of whom (n = 216/360, 60%) were females. The
      majority of patients (n = 153/360, 42.5%) were 25-34 years old with mean age of
      35.5+ 8.8 standard deviation. The overall prevalence of OIs was (n = 71/360,
      19.7%). Tuberculosis (n = 35/360, 9.72%) followed by oral candidiasis (n =
      18/360, 5%) and diarrhea (n = 12/360, 3.3%) were the most frequently observed
      OIs. CD4 count less than 200/mm3 (OR = 4.933, P < 0.001), World Health
      Organization (WHO) clinical stage III (OR = 9.418, P < 0.001) and IV (OR =
      22.665, P < 0.001) were found to have strong association with acquisition of OIs.
      CONCLUSIONS: Tuberculosis, oral candidiasis and diarrhea were the leading OIs
      encountered by HIV-infected patients. CD4 count less than 200/mm3 and advanced
      WHO clinical stages of the disease were found to be predictors of OIs.
      Interventions aimed at preventing and treating HIV associated OIs are crucial.
      Initiation of ART before the CD4 count drops below 350 should be encouraged.

PMID- 24330923
TI  - [Overall and intensively conduct the prevention of blindness in China: explaining
      the National Plan for the Prevention of Blindness (2012-2015)].
AB  - The National Plan for the Prevention of Blindness(2012-2015) issued by Ministry
      of Health and China Disabled Person Federation last year is an important
      procedure for further promoting the prevention of blindness and reach the great
      goal for eliminating the avoidable blindness by 2020 in China. The Plan clearly
      describe the social nature of the prevention of blindness, correctly explain the
      current situation for prevention of blindness in China, put forward the guidance
      idea, working principles, goals and contents, and the guarantee measures in the
      next four years in the prevention of blindness in China. The leaders in
      ophthalmology and ophthalmologists in China should learn and practice the Plan
      for the more progress in the prevention of blindness. 

PMID- 24330922
TI  - Cost drivers of inpatient mental health care: a systematic review.
AB  - Aims. New reimbursement schemes for inpatient mental health care are imminent in
      the UK and Germany. The shared intention is to reflect cost differences between
      patients in reimbursement rates. This requires understanding of patient
      characteristics that influence hospital resource use. The aim of this review was
      to show which associations between mental health care per diem hospital costs and
      patient characteristics are supported by current evidence. Methods. A systematic
      review of the literature published between 1980 and 2012 was carried out. The
      search strategy included electronic databases and hand-searching. Furthermore,
      reference lists, citing articles and related publications were screened and
      experts were contacted. Results. The search found eight studies. Dispersion in
      per diem costs was moderate, as was the ability to explain it with patient
      characteristics. Six patient characteristics were identified as the most relevant
      variables. These were (1) age, (2) major diagnostic group, (3) risk, (4) legal
      problems, (5) the ability to perform activities of daily living and (6) presence
      of psychotic or affective symptoms. Two non-patient-related factors were
      identified. These were (1) day of stay and (2) treatment site. Conclusions.
      Idiosyncrasies of mental health care complicated the prediction of per diem
      hospital costs. More research is required in European settings since
      transferability of results is unlikely. 

PMID- 24330924
TI  - [Cautious choice of new intraocular lenses in patients with cataract
      rehabilitation surgery in China].
AB  - We must choose new intraocular lenses (IOL) cautiously and strictly in patients
      with cataract rehabilitation surgery in China because of following reasons.
      Firstly, there are no differences in visual acuity between traditional poly
      methylmethacrylate (PMMA) IOL implantation group and new IOL (multifocal IOL,
      aspherical IOL) implantation group. Secondarily, there are many factors which
      affect visual performance after cataract surgery. Thirdly, many patients with
      cataract can not afford new intraocular lenses .Fourthly, there are several
      faultiness and clinical problems in new intraocular lenses. Therefore, correct
      selection of IOL should be affordable PMMA IOL in cataract rehabilitation surgery
      in China. 

PMID- 24330925
TI  - [Prevalence and causes of blindness and moderate and severe visual impairment
      among adults aged 50 years or above in Yongchuan District of Chongqing City: the
      China Nine-Province survey].
AB  - OBJECTIVE: To investigate the prevalence and causes of blindness and moderate and
      severe visual impairment among adults aged 50 years or above in Yongchuan of
      Chongqing City, China. METHODS: It was a population-based cross-section
      study.Geographically defined cluster sampling was used in randomly selecting 5663
      individuals aged >= 50 years in Yongchuan District. The survey was preceded by a
      pilot study where operational methods were refined and quality assurance
      evaluation was carried out. All participants were enumerated through village
      registers followed door-to-door visits.Eligible individuals were invited to
      receive visual acuity measurement and eye examination. Prevalence of blindness
      and moderate and severe visual impairment was calculated according to different
      age, gender or education. And the reasons of blindness were analyzed.Statistical
      analyses were performed using Stata/SE Statistical Software, release 9.0. Chi
      square test was used to investigate the association of age, gender and education
      with presenting and best corrected visual acuity. RESULTS: Five thousands six
      hundreds and sixty-three individuals were enumerated and 5390 persons were
      examined, the response rate was 95.18%. Based on the criteria of World Health
      Organization visual impairment classification in 1973, the prevalence of
      blindness and moderate and severe visual impairment defined as best corrected
      visual acuity was 2.12% (114/5390) and 5.40% (291/5390) respectively. The
      prevalence of blindness and moderate and severe visual impairment defined as
      presenting visual acuity was 2.49% (134/5390) and 10.71% (577/5390) respectively.
      The prevalence of blindness and moderate and severe visual impairment was higher
      in aged (trend chi(2) = 951.32, P = 0.000) , female (chi(2) = 33.35, P = 0.000)
      and illiterate (trend chi(2) equals; 141.32, P = 0.000) persons. Cataract was
      still the first leading cause of blindness and visual impairment.Un-corrected
      refractive error also was the main cause of visual impairment. CONCLUSIONS: The
      prevalence of blindness and moderate and severe visual impairment is relatively
      higher among older adults aged 50 years or above in Yongchuan District. The first
      leading cause of blindness and visual impairment is still cataract.

PMID- 24330926
TI  - [Prevalence and causes of blindness and moderate and severe visual impairment
      among adults aged 50 years or above in Longyao County of Hebei Province:the China
      Nine-Province survey].
AB  - OBJECTIVE: To investigate the prevalence and causes of blindness and moderate and
      severe visual impairment among adults aged >= 50 years in Longyao County, Hebei
      Province, China. METHODS: It was a population-based cross-section
      study.Geographically defined cluster sampling was used in randomly selecting 5527
      individuals aged >= 50 years in Longyao County. The survey was preceded by a
      pilot study where operational methods were refined and quality assurance
      evaluation was carried out. All participants were enumerated through village
      registers followed door-to-door visits.Eligible individuals were invited to
      receive visual acuity measurement and eye examination. Prevalence of blindness
      and moderate and severe visual impairment was calculated according to different
      age, gender or education. And the reasons of blindness were analyzed.Statistical
      analyses were performed using Stata/SE Statistical Software, release 9.0. Chi
      square test was used to investigate the association of age, gender and education
      with presenting and best corrected visual acuity. RESULTS: Five thousands five
      hundreds and twenty-seven individuals were enumerated and 5051 persons were
      examined, the response rate was 91.39%. Based on the criteria of World Health
      Organization visual impairment classification in 1973, the prevalence of
      blindness and moderate and severe visual impairment defined as best corrected
      visual acuity was 1.05% (53/5051) and 3.46% (175/5051) respectively. The
      prevalence of blindness and moderate and severe visual impairment defined as
      presenting visual acuity was 1.48% (75/5051) and 7.94% (401/5051) respectively.
      The prevalence of blindness and moderate and severe visual impairment was higher
      in aged (trend chi(2) = 897.27, P = 0.000) , female (chi(2) = 30.32, P = 0.000),
      illiterate (trend chi(2) = 83.20, P = 0.000) persons. Cataract was still the
      first leading cause of blindness. Un-corrected refractive error also was the main
      cause of visual impairment. CONCLUSIONS: The prevalence of blindness and moderate
      and severe visual impairment is relatively lower among China Nine Province
      Survey. The first leading cause of blindness and visual impairment is still
      cataract.

PMID- 24330927
TI  - [Prevalence and influence of diabetic retinopathy in populations at the age of >=
      40 years in Luzhou City, Sichuan Province in 2011].
AB  - OBJECTIVE: To estimate the prevalence rate and risk factors of diabetic
      retinopathy(DR) in residents at the age of >= 40 years in Luzhou, Sichuan
      Province. METHODS: A multistage, stratified cluster random sampling method was
      used to select 7 communities of 8002 permanent residents ( >= 40 years old) for
      diabetes screened from May to December 2011 in Luzhou, Sichuan Province.Reference
      to the diagnostic criteria for diabetes recommended by World Health Organization
      in 1999, to the 1374 diabetes screening out patients with questionnaire, physical
      examination, fasting plasma glucose, 2-hours postprandial plasma glucose,
      glycosylated hemoglobin(HbAlc) and visual acuity, ocular diseases, fundus
      examination, etc.Some patients with fundus fluorescein angiography to the DR
      diagnosis, diagnostic criteria with reference to the diagnosis standard made by
      Chinese Ocular Fundus Diseases Society, Chinese Ophthalmological Society, Chinese
      Medical Association in 1984. Rates between the groups were compared using chi(2)
      test, trend chi(2) test or Fisher exact test, using multivariate analysis of risk
      factors associated with DR screening. RESULTS: A total of 8002 people were chosen
      and invited to take part in the project, 7478 persons completed the study, the
      overall response rate was 93.48%.One thousand three hundreds and seventy-four
      persons were diagnosed as diabetic patients, which took the proportion of 18.37%
      of the selected population, while 214 DR patients were found with the DR
      prevalence of 15.57%, occupying 2.86% of the total.Of 214 patients, 194 cases
      were non-proliferative diabetic retinopathy, making up 90.65% of DR patients,
      while 7 cases were found to be proliferative diabetic retinopathy, constitute
      9.35% of DR patients. Multi-factor analysis manifest that there were close
      relationship between diabetic duration (trend chi(2) = 189.21, P < 0.01) , the
      level of HbAlc (chi(2) = 30.021, P < 0.01) , coronary heart disease (chi(2) =
      4.075, P = 0.044) and DR prevalence. CONCLUSIONS: The prevalence of DR is high in
      the diabetic residents in Luzhou, Sichuan Province. Diabetic duration, the level
      of HbAlc and coronary heart disease are the significant factors to influence DR
      development. These results indicate that the changes of the level of HbAlc are
      closely related to the genesis and development of DR among the diabetic patients.

PMID- 24330928
TI  - [Prevalence and causes of blindness and moderate and severe visual impairment
      among adults aged 50 years or above in Changji City of Xinjiang Uygur Autonomous
      Region: the China Nine-Province survey].
AB  - OBJECTIVE: To investigate the prevalence and causes of blindness and moderate and
      severe visual impairment among adults aged >= 50 years in Changji City of
      Xinjiang Uygur Autonomous Region, China. METHODS: It was a population-based cross
      section study.Geographically defined cluster sampling was used in randomly
      selecting 5714 individuals aged >= 50 years in Changji City. The survey was
      preceded by a pilot study where operational methods were refined and quality
      assurance evaluation was carried out. All participants were enumerated through
      village registers followed door-to-door visits.Eligible individuals were invited
      to received visual acuity measurement and eye examination. Prevalence of
      blindness and moderate and severe visual impairment was calculated according to
      different age, gender or education. And the reasons of blindness were
      analyzed.Statistical analyses were performed using Stata/SE Statistical Software,
      release 9.0. Chi-square test was used to investigate the association of age,
      gender and education with presenting and best corrected visual acuity. RESULTS:
      Five thousands seven hundreds and fourteen individuals were enumerated and 5250
      persons were examined, the response rate was 91.88%. Based on the criteria of
      World Health Organization visual impairment classification in 1973, the
      prevalence of blindness and moderate and severe visual impairment defined as best
      corrected visual acuity was 0.74% (39/5250) and 3.83% (201/5250) respectively.
      The prevalence of blindness and moderate and severe visual impairment defined as
      presenting visual acuity was 1.33% (70/5250) and 8.02% (421/5250) respectively.
      The prevalence of blindness and moderate and severe visual impairment was higher
      in aged (trend chi(2) = 617.06, P = 0.000) , illiterate (trend chi(2) = 222.35, P
      = 0.000) persons. Cataract and was the first leading cause of blindness and
      visual impairment, the retinal diseases, including age-related macular
      degeneration, high myopic retinopathy, and diabetic retinopathy, were the second
      cause of blindness and visual impairment.Un-corrected refractive error was also
      the important cause of the visual blindness. CONCLUSIONS: The prevalence of
      blindness and moderate and severe visual impairment is not high among older
      adults aged >= 50 years in Changji City. The first main causes of blindness and
      visual impairment includes cataract, retinal diseases and un-corrected refractive
      error.

PMID- 24330930
TI  - [Optical coherence tomography predictive factors for idiopathic macular hole
      surgery outcome].
AB  - OBJECTIVE: To evaluate the use of preoperative optical coherence tomography (OCT)
      image and some related indexes as predictive factors for the visual outcomes of
      the idiopathic macular hole (IMH) after pars plana vitrectomy and the internal
      limiting membrane (ILM) peeling surgery. METHODS: This was a case-series study.
      Twenty-five eyes of 23 IMH patients undergoing a successful vitrectomy and ILM
      peeling surgery and following up more than 6 months were included in this
      retrospective study. Of the 23 patients, 6 were male and 17 were female. The
      median patient age was 67-year old (range 63 to 71 years). The median duration of
      IMH was 6 months (range 3.5 to 12.0 months).In the patients, the macular hole was
      found in 9 eyes at stage II, 11 eyes at stage III, and 5 eyes at stage IV. Best
      corrected visual acuity (BCVA) were examined before and after the surgery. The
      minimum diameter (a) , the height (b) and the base diameter (c) of macular holes
      were measured by OCT. According to the indexes, macular hole index (MHI, b/c) ,
      tractional hole index (THI, b/a) , diameter hole index (DHI, a/c) were
      calculated, respectively. Spearman rank correlation analysis was performed to
      understand the correlations between postoperative BCVA and the related indexes.
      Cut-off values were obtained for MHI and THI, respectively, from receiver
      operating characteristic (ROC) curve analysis. RESULTS: The median preoperative
      BCVA was 0.100(range 0.050 to 0.180). The median MHI, THI and DHI was 0.476(range
      0.416 to 0.684), 1.048(range 0.761 to 1.346) and 0.536(range 0.431 to 0.645),
      respectively. The median 3-month postoperative BCVA was 0.150 (range 0.120 to
      0.275), markedly improved after surgery (Mann-Whitney U test:P = 0.002) . The
      median latest postoperative BCVA was 0.250 (range 0.135 to 0.350), also markedly
      improved (Mann-Whitney U test, P = 0.002) . MHI, THI and preoperative BCVA
      correlated significantly with postoperative BCVA by Spearman rank correlation
      analysis (rMHI = 0.481, P = 0.015; rTHI= 0.516, P = 0.008; preoperative BCVA =
      0.560, P = 0.004, respectively). Areas under the curve of 0.740 and 0.760 for MHI
      and THI were obtained respectively. Cut-off values of 0.475 and 0.973 were
      obtained for MHI and THI, respectively, from ROC curve analysis. Postoperative
      BCVAs in the MHI >= 0.475 group and in the THI >= 0.973 group was better than
      that in the MHI < 0.475 and in the THI < 0.973 group, respectively (Mann-Whitney
      U test:P MHI = 0.013, P THI = 0.008) . CONCLUSION: An MHI >= 0.475 or a THI >=
      0.973 may be predictive factors for a good visual prognosis after IMH surgery.

PMID- 24330929
TI  - [Prevalence and causes of blindness and moderate and severe visual impairment
      among adults aged 50 years or above in Luxi County of Yunnan Province: the China
      Nine-Province survey].
AB  - OBJECTIVE: To investigate the prevalence and causes of blindness and moderate and
      severe visual impairment among adults aged >= 50 years in Luxi County of Yunnan
      Province, China. METHODS: It was a population-based cross-section study.
      Geographically defined cluster sampling was used in randomly selecting 5575
      individuals aged >= 50 years in Luxi County. The survey was preceded by a pilot
      study where operational methods were refined and quality assurance evaluation was
      carried out. All participants were enumerated through village registers followed
      door-to-door visits.Eligible individuals were invited to receive visual acuity
      measurement and eye examination. Prevalence of blindness and moderate and severe
      visual impairment was calculated according to different age, gender or education.
      And the reasons of blindness were analyzed.Statistical analyses were performed
      using Stata/SE Statistical Software, release 9.0. Chi-square test was used to
      investigate the association of age, gender and education with presenting and best
      corrected visual acuity. RESULTS: Five thousands five hundreds and seventy-five
      individuals were enumerated and 5151 persons were examined, the response rate was
      92.39%. Based on the criteria of World Health Organization visual impairment
      classification in 1973, the prevalence of blindness and moderate and severe
      visual impairment defined as best corrected visual acuity was 4.95% (255/5151)
      and 9.51% (490/5151) , respectively. The prevalence of blindness and moderate and
      severe visual impairment defined as presenting visual acuity was 5.40% (278/5151)
      and 15.84% (816/5151) , respectively. The prevalence of blindness and moderate
      and severe visual impairment was higher in aged (chi(2) = 1349.21, P = 0.000) ,
      illiterate (chi(2) = 203.55, P = 0.000) persons. Cataract was still the first
      leading cause of blindness and visual impairment. CONCLUSIONS: The prevalence of
      blindness and moderate and severe visual impairment is highest in China Nine
      Province Survey among older adults aged >= 50 years in Luxi County. The first
      leading cause of blindness and visual impairment is still cataract.

PMID- 24330931
TI  - [The clinical characteristics and prognosis of 92 cases of delayed occurrence of
      retinoblastoma].
AB  - OBJECTIVE: To retrospectively summarize the clinical features, diagnosis and
      treatment of retinoblastoma (RB) patients in the children aged 5 years or above.
      METHODS: This was a case-series study. Total of 92 patients (107 eyes) with RB
      aged 5 years or above in Department of Pediatric,Beijing Tongren Hospital from
      September 2005 to May 2010 were included in the study. The diagnosis of RB was
      established using clinical examination and histopathology analysis.Statistical
      analysis in the characteristics of disease and initial symptoms was performed in
      92 cases. Kaplan-Meier curve was employed to analyze the survival function.
      RESULTS: (1) The medium age of the patients was 6.25-year. Male accounted for
      66.30% (61/92) and female was 33.69% (31/92) . According to the results of
      statistical scatter diagram, the age of the disease onset was ranged from 5.00 to
      8.33 years. Percentile for age 5.77, 5.83 and 7.85 years were the 25th, 50th,
      75th respectively. (2) In 92 cases, 83.69% (77/92) of the patients were
      unilateral RB and 16.31% (15/92) were bilateral RB. (3) Leukocoria was the most
      common manifestation in the diagnosis early RB, accounting for 55.43% (51/92)
      .Secondary symptoms were blurred vision, eye redness and photophobia, accounting
      for 23.91% (22/92). Other symptoms included strabismus, proptosis, glaucoma and
      the abnormal in fundus examination, accounting for 20.64% (19/92) .No family
      history of RB was found in all of cases studied. (4) Among 107 eyes with RB, 76
      eyes were enucleated up to February 2013. The rate of enucleation was 71.02%. (5)
      By February 2013, the average following-up time was 39 months, during the time 1
      case was lost, 6 cases were dead, the overall survival rate was 93.46% (85/92) .
      The result of Kaplan-Meier curve showed that the estimates of 5-year expected
      average total survival time was (72.61 +/- 1.89) months(95%confidence interval
      was 68.9-76.3 months). CONCLUSIONS: Unilateral RB are the most common cases in
      the age of 5 years or above, and the most common symptom is Leukocoria.Overall
      survival rate of older RB patient is high with comprehensive treatment.

PMID- 24330932
TI  - [Protective effect of haliotidis on the oxidative damage in the human lens
      epithelial cells].
AB  - OBJECTIVE: To study the influence of haliotidis extractive on the oxidative
      damage in the human lens epithelial cells cultured in vitro. METHODS:
      Experimental study. Cultured human lens epithelial cells in vitro were intervened
      with hydrogen peroxide caused oxidative damage model, at the same time added
      different concentrations of concha haliotidis extractive. With control experiment
      research cells were divided into the blank control group, positive control group
      hydrogen peroxide group and hydrogen peroxide and different concentrations of
      concha haliotidis group, and on the first, third, fifth day the activity of
      Cultured human lens epithelial cells were detected with Cell Counting Kit-8 (CCK
      8) , cellular proliferation and morphological changes were observed with interred
      phase contrast microscope, and then on the third day chemical colorimetric were
      used to detect the homogenates superoxide dismutase(SOD), glutathione(GSH) and
      malondialdehyde (MDA) level. RESULTS: (1) At different time points there were
      variations between the activity of HLEC in each experimental group, Among each
      experimental group HLEC OD value of the cell vitality at 1 d, 3 d, 5 d ,
      respectively were blank control group: 0.88, 1.28, 1.32; Positive control group:
      0.73, 1.02, 1.06; 0.001% concha haliotis extract group: 0.73, 1.03, 1.06; 0.01%
      concha haliotis extract group: 0.76, 1.10, 1.13; 0.1% concha haliotis extract
      group: 0.79, 1.22, 1.21; 0.3% concha haliotis extract group: 0.79, 1.21, 1.21;
      the difference between groups was statistically significant (P < 0.05) (1 d, F =
      23 922.42, P < 0.05;3 d, F = 120 605.86, P < 0.05; 5 d, F = 150 939.45, P <
      0.05). H2O2 made the vitality of the cells reduce, concha haliotidis enhance its
      vitality, and in a certain range of time and concentrations there was dependence,
      with which the third day and 0.1% was the best. (2) After adding H2O2, the SOD
      and GSH level of HLEC reduced,(SOD 158.05 U/mgprot,GSH 15.05 mg/gprot) but MDA
      increased to 18.11 nmol/mgprot, concha haliotidis groups made the increase of
      antioxidant level(SOD 188.64 U/mgprot,GSH 21.05 mg/1000 mgprot)and the decrease
      of lipid peroxidation in oxidative damaged HLECs(MDA 14.16 nmol/mgprot), change
      had a statistical significance(P < 0.05) (SOD: F = 983.04, P < 0.05; GSH: F =
      444.44, P < 0.05; MDA: F = 830.52, P < 0.05). (3)The chromatin of the positive
      control group concentrated and aggregated obviously, the aggregation of chromatin
      in concha haliotidis group lightened. CONCLUSION: The concha haliotidis can
      protect the cultured human lens epithelial cells in vitro which are oxidative
      injured, increased intracellular antioxidant levels, reduce the generation of
      hazardous products.

PMID- 24330933
TI  - [Effects of transforming growth factor-beta2 on transdifferentiation,
      extracellular matrix synthesis and connective tissue growth factor expression of
      human lens epithelium cells].
AB  - OBJECTIVE: To explore the effects of transforming growth factor-beta2 (TGF-beta2)
      on the transdifferentiation, extracellular matrix synthesis and connective tissue
      growth factor (CTGF) expression in human lens epithelium cells (HLEC) in vitro.
      METHODS: HLEC were incubated with different concentrations of TGF-beta2 (0.0,
      0.1, 1.0 and 10.0 ug/L) for 24 h in vitro. The morphological changes of HLEC were
      observed under inverted phase-contrast microscope. The expression of CTGF and
      alpha-smooth muscle actin (alpha-SMA, as a landmark protein of epithelial
      mesenchymal transition) in HLEC was measured by immunofluorescence method. Real
      time PCR and Western blot were used to evaluate the expression of CTGF, alpha
      SMA, fibronectin (Fn) and COL-I (as the major components of extracellular matrix)
      after stimulating by TGF-beta2. RESULTS: Normal HLEC presented polygonal shape
      and were anchorage-dependent. After incubated with different concentrations of
      TGF-beta2 for 24 h, the morphology of polygonal HLEC was changed into fibroblast
      like shape and changed from monolayer and to multilayer cells, and the
      intercellular space became bigger. CTGF and alpha-SMA were expressed in the
      cytoplasm after induction of TGF-beta2. Expression of CTGF in HLEC was increased
      with increasing concentrations of TGF-beta2 (CTGF protein expression: 0.53 +/-
      0.03, 0.73 +/- 0.01, 0.65 +/- 0.03 in cells cultured with 0.1, 1.0 and 10 ug/L
      TGF-beta2, respectively; CTGF gene induction: 1.00 +/- 0.00, 7.18 +/- 0.41, 12.88
      +/- 0.45, 32.84 +/- 1.61 in cells cultured with 0.0, 0.1, 1.0 and 10.0 ug/L TGF
      beta2, respectively) (F = 77.55, P < 0.05; F = 379.0, P < 0.05). TGF-beta2 could
      induce HLEC transdifferentiation and accelerate. alpha-SMA expression was
      increased by TGF-beta2 dose-dependently (protein expression: 0.48 +/- 0.01,0.78
      +/- 0.04, 0.69 +/- 0.04; gene induction: 1.00 +/- 0.00, 2.30 +/- 0.22, 3.1 +/-
      0.21, 3.86 +/- 0.10) (F = 62.73, P < 0.05; F = 80.22, P < 0.05). TGF-beta2 also
      promoted expression of Fn and COL-I in a dose-dependent manner (COL-I gene
      induction: 1.00 +/- 0.00, 5.52 +/- 0.96, 18.31 +/- 1.2, 82.51 +/- 1.45;COL-I
      protein expression: 0.78 +/- 0.05, 1.15 +/- 0.11, 2.16 +/- 0.14; Fn gene
      induction: 1.00 +/- 0.00, 2.36 +/- 0.25, 3.27 +/- 0.24, 4.25 +/- 0.24; Fn protein
      expression: 0.64 +/- 0.01,0.95 +/- 0.02, 1.23 +/- 0.14) (F = 1881.52, 105.30, P <
      0.05; F = 64.44, 51.81, P < 0.05). CONCLUSION: TGF-beta2 induces the expression
      of CTGF by HLEC, promotes transdifferentiation of and extracellular matrix
      synthesis by HLEC.

PMID- 24330934
TI  - [Experimental study on the treatment of non-tuberculous mycobacterial keratitis].
AB  - OBJECTIVE: To explore the optimal treatment for non-tuberculous mycobacterial
      keratitis (NTMK). METHODS: Experimental study.Fifty-one New Zealand white rabbits
      were inoculated with non-tuberculous mycobacteria (NTM) to establish the animal
      model of NTMK. Eyes with NTMK were randomly divided into 7 groups and topically
      treated with amikacin (2.5%) (B), gatifloxacin (3%) (C), azithromycin (1%) (D),
      amikacin (2.5%) plus gatifloxacin(3%) (E) , amikacin (2.5%) plus gatifloxacin
      (3%) combined with debridement (F), early lamellar keratoplasty (G) and balanced
      salt water (as a control) (A). All the drugs were administered 8 times per day
      within initial 7 days followed by 4 times per day after 1 week. The clinical
      manifestations of each rabbit were observed and recorded every week. The score of
      clinical manifestations before and after treatment does not meet the normal
      distribution, so it was presented by the median +/- quantile interval and
      compared with rank sum test and SNK test. Fisher exact test was used to compare
      differences in the distribution of presenting the healing rate of keratitis.
      RESULTS: After 1 week treatment, six eyes were cured in group G, and none were
      cured in other groups, the scores of clinical manifestations of group B, C, D, E,
      F and G were 6 +/- 4, 8 +/- 2, 6 +/- 4, 8 +/- 3, 7 +/- 4, 3 +/- 1, they were
      higher than that of group A (q = 20.36, 11.43, 19.21, 16.93, 18.64, 37.50, P <
      0.05). After 2 weeks, the scores of group B, C, E, F and G were higher than that
      of group A (q = 23.50, 16.71, 15.21, 12.43, 30.87, P < 0.05), and the healing
      rate of group G was higher than that of group A. After 3 weeks, the score of
      clinical manifestations of group B, D, F and G was higher than that of group A,
      and the healing rate of group F and G was higher than that of group A. After 4
      weeks, the inflammation of group F and G were healed, and a little inflammation
      remained in the eye of group A. The score of clinical manifestations of group D,
      E, F and G was higher than that of group A. None was detected in the bacterial
      culture after 4 weeks. In histopathological examination, there were integrated
      and proliferated corneal epithelium, fibroblast cells proliferation in the eyes
      of experimental groups was found, while corneal cells edema, stroma degeneration
      and necrosis with lymphocytes and plasma cells in the ulcerated lesion in the
      corneal stromal of group A. CONCLUSIONS: Amikacin, gatifloxacin or azithromycin
      is effective in arresting NTM, while antibiotic combined with debridement is more
      effective and early lamellar keratoplasty is the most rapid and thorough
      treatment of NTMK.

PMID- 24330935
TI  - [Drug dynamics research of salvia miltiorrhiza in rabbit plasma and aqueous humor
      after intravenous injection].
AB  - OBJECTIVES: To assess the permeability of Danshensu at blood-ocular barrier and
      its characteristics of pharmacokinetics by respectively measuring the
      concentrations of Danshensu in blood plasma and aqueous humor of the rabbit with
      the high performance liquid chromatography(HPLC). METHODS: It was an experimental
      study. Seventy-two white rabbits were split into three groups: control group (6
      rabbits), plasma group (6 rabbits) and aqueous humor group (60 rabbits). After
      0.85% salt water (control group)or salvia miltiorrhiza (1.0 g/kg) (plasma and
      aqueous group) was injected into the vein of auris-edge. Samples of blood and
      aqueous humor were obtained for analysis . The analytical column was a BDS C18
      stainless steed column(5 um, 4.6 mm* 250 mm); Precolumn:YWGC18; the mobile phase
      consists of acetonitrile and 0.01 mol/L KH2PO4 (8:92, adjusted to pH = 2.8 with
      phosphoric acid). The UV detector was set at 279 nm; the flow rate was 1.0
      ml/min;and the column temperature was ordinary temperature. RESULTS: The plasma
      concentration-time curves of Salvia miltiorrhiza fitted three-compartment model.
      t1/2 beta (elimination half time): 5.661 min; Cmax (peak concentration): 727.29
      mg/L; Tmax(peak time ): 0 min. The aqueous humor concentration-time curves fitted
      two-compartment model. t1/2 beta: 147.663 min; Cmax: 38.62 mg/L; Tmax: 25 min.
      CONCLUSIONS: HPLC is a sensitive, specific and accurate method that can be used
      in pharmacokinetics research on ocular tissue of rabbit for Danshensu, Salvia
      miltiorrhiza that is dissolvable in water can pass through the blood-ocular
      barrier after intravenous injection with a relatively stable concentration of
      danshensu in aqueous humor resulting from a slow rate of removal.

PMID- 24330936
TI  - [Progress in sustained-release drug delivery system for treatment of posterior
      segment eye diseases].
AB  - There is an urgent requirement to find effective therapeutic procedures for the
      treatment of refractory eye diseases of posterior segment such as posterior
      uveitis, proliferative vitreoretinopathy, and macular edema associated with
      diabetes and retinal vein occlusion. Due to systemic side effect developed from
      systemic drug administration and the low efficiency of topical drug
      administration, implantable drug devices for the treatment of posterior segment
      diseases have been explored. In recent years, three different intraocular
      implantable devices (ganciclovir, fluocinolone acetonide and dexamethasone) have
      been approved by FDA and showed exciting clinical efficacy. However, these
      devices have surgical complications and the drug-related side effects. Recently,
      transscleral drug delivery to the posterior segment has been investigated.
      Transscleral drug delivery has advantages of large scleral surface area, better
      safety profile, easily drug administration and could evolve into an effective
      route with the use of novel biomaterials and the study of drug delivery methods. 

PMID- 24330937
TI  - [Research progress in intraocular pressure monitoring of glaucoma].
AB  - Elevation of intraocular pressure (IOP) is a major risk factor for the
      development and the progression in glaucoma optic nerve damage. The reduction of
      IOP remains mainstream strategy of glaucoma therapy. A large fluctuation of IOP
      in the circadian rhythm may play a role in the optic nerve damage in glaucoma
      progression. IOP monitoring provides important information of IOP mean, peak and
      fluctuation to assist the diagnosis and treatment of glaucoma. With the
      development of technology, the commonly used methods of IOP monitoring including
      IOP measurement for diurnal, 24 hours, and habitual body position have evolved to
      continuous IOP-monitoring using novel device. The influencing factors including
      tonometer, body position and the light have been taken into account for the
      reliability of IOP measurement. In this review, we summarized the recent progress
      in IOP monitoring and the factors affecting the IOP measurements and discussed
      immense opportunity of IOP-monitoring to better diagnose and to treat for
      glaucoma. 

PMID- 24330938
TI  - [Recent advances in dry eye: etiology, pathogenesis and management].
AB  - Dry eye is one of the most common and multifactorial disease of the ocular
      surface that results in ocular discomfort, blurred vision, reduced quality of
      life, and decreased productivity. Recent advances in our knowledge of the
      causation of dry eye open opportunities for improving diagnosis , and disease
      management and for developing new, more effective therapies to manage this widely
      prevalent and debilitating disease state. In light of the above knowledge, the
      present article reviews the newer theories and reports on etiology , pathogenesis
      and management of dry eye. 

PMID- 24330939
TI  - alpha-Retinol and 3,4-didehydroretinol support growth in rats when fed at
      equimolar amounts and alpha-retinol is not toxic after repeated administration of
      large doses.
AB  - Dietary alpha-carotene is present in oranges and purple-orange carrots. Upon the
      central cleavage of alpha-carotene in the intestine, alpha-retinal and retinal
      are formed and reduced to alpha-retinol (alphaR) and retinol. Previous reports
      have suggested that alphaR has 2% biopotency of all-trans-retinyl acetate due in
      part to its inability to bind to the retinol-binding protein. In the present
      work, we carried out three studies. Study 1 re-determined alphaR's biopotency
      compared with retinol and 3,4-didehydroretinol in a growth assay. Weanling rats
      (n 40) were fed a vitamin A-deficient diet for 8 weeks, divided into four
      treatment groups (n 10/group) and orally dosed with 50 nmol/d retinyl acetate
      (14.3 MUg retinol), alpha-retinyl acetate (143 MUg alphaR), 3,4-didehydroretinyl
      acetate (14.2 MUg DR) or cottonseed oil (negative control). Supplementation was
      continued until the control rats exhibited deficiency signs 5 weeks after the
      start of supplementation. Body weights and AUC values for growth response
      revealed that alphaR and DR had 40-50 and 120-130% bioactivity, respectively,
      compared with retinol. In study 2, the influence of alphaR on liver ROH storage
      was investigated. The rats (n 40) received 70 nmol retinyl acetate and 0, 17.5,
      35 or 70 nmol alpha-retinyl acetate daily for 3 weeks. Although liver retinol
      concentrations differed among the groups, alphaR did not appreciably interfere
      with retinol storage. In study 3, the accumulation and disappearance of alphaR
      over time and potential liver pathology were determined. The rats (n 15) were fed
      3.5 MUmol/d alpha-retinyl acetate for 21 d and the groups were killed at 1-, 2-
      and 3-week intervals. No liver toxicity was observed. In conclusion, alphaR and
      didehydroretinol are more biopotent than previously reported at sustained
      equimolar dosing of 50 nmol/d, which is an amount of retinol known to keep rats
      in vitamin A balance.

PMID- 24330940
TI  - Outbreak of Salmonella enterica Goldcoast infection associated with whelk
      consumption, England, June to October 2013.
AB  - An increase in the number of cases of Salmonella enterica serotype Goldcoast
      infection was observed in England during September 2013. A total of 38 cases were
      reported, with symptom onset dates between 21 June and 6 October 2013.
      Epidemiological, environmental, microbiological and food chain evidence all
      support the conclusion that this outbreak was associated with eating whelks
      processed by the same factory. Whelks are a novel vehicle of Salmonella infection
      and should be considered when investigating future outbreaks.

PMID- 24330941
TI  - Tularaemia in a brown hare (Lepus europaeus) in 2013: first case in the
      Netherlands in 60 years.
AB  - Tularaemia has not been reported in Dutch wildlife since 1953. To enhance
      detection, as of July 2011, brown hares (Lepus europaeus) submitted for
      postmortem examination in the context of non-targeted wildlife disease
      surveillance, were routinely tested for tularaemia by polymerase chain reaction
      (PCR). Francisella tularensis subspecies holarctica infection was confirmed in a
      hare submitted in May 2013. The case occurred in Limburg, near the site of the
      1953 case. Further surveillance should clarify the significance of this finding.

PMID- 24330942
TI  - Case of vaccine-associated measles five weeks post-immunisation, British
      Columbia, Canada, October 2013.
AB  - We describe a case of vaccine-associated measles in a two-year-old patient from
      British Columbia, Canada, in October 2013, who received her first dose of measles
      containing vaccine 37 days prior to onset of prodromal symptoms. Identification
      of this delayed vaccine-associated case occurred in the context of an outbreak
      investigation of a measles cluster.

PMID- 24330943
TI  - A Shigella sonnei outbreak traced to imported basil--the importance of good
      typing tools and produce traceability systems, Norway, 2011.
AB  - On 9 October 2011, the University Hospital of North Norway alerted the Norwegian
      Institute of Public Health (NIPH) about an increase in Shigella sonnei infections
      in Tromso. The isolates had an identical 'multilocus variable-number tandem
      repeat analysis' (MLVA) profile. Most cases had consumed food provided by
      delicatessen X. On 14 October, new S. sonnei cases with the same MLVA-profile
      were reported from Sarpsborg, south-eastern Norway. An outbreak investigation was
      started to identify the source and prevent further cases. All laboratory
      confirmed cases from both clusters were attempted to be interviewed. In addition,
      a cohort study was performed among the attendees of a banquet in Tromso where
      food from delicatessen X had been served and where some people had reported being
      ill. A trace-back investigation was initiated. In total, 46 cases were confirmed
      (Tromso= 42; Sarpsborg= 4). Having eaten basil pesto sauce or fish soup at the
      banquet in Tromso were independent risk factors for disease. Basil pesto was the
      only common food item that had been consumed by confirmed cases occurring in
      Tromso and Sarpsborg. The basil had been imported and delivered to both
      municipalities by the same supplier. No basil from the specific batch was left on
      the Norwegian market when it was identified as the likely source. As a result of
      the multidisciplinary investigation, which helped to identify the source, the
      Norwegian Food Safety Authority, together with NIPH, planned to develop
      recommendations for food providers on how to handle fresh plant produce prior to
      consumption.

PMID- 24330947
TI  - Detection of IgG antibody against Crimean-Congo haemorrhagic fever virus using
      ELISA with recombinant nucleoprotein antigens from genetically diverse strains.
AB  - Crimean-Congo haemorrhagic fever virus (CCHFV) has the propensity to cause
      nosocomial infections with a high fatality rate. Handling the virus requires
      biosafety level-4 facilities, limiting accessibility for many laboratories.
      Advances in molecular techniques have allowed preparation of safe recombinant
      antigens that have application in diagnosis and serosurveillance of CCHFV. The
      aim of this study was to determine genetic diversity in CCHFV based on all
      available complete sequence data for the S gene encoding CCHFV nucleoprotein (NP)
      and antibody cross-reactivity between the NP of a South African isolate and the
      NP of a Greek isolate (AP92), the most genetically diverse CCHFV strain. The
      nucleotide sequence diversity and amino-acid diversity between genotypes, within
      genotypes and the pairwise distances were calculated for a dataset of 45 CCHFV
      isolates retrieved from GenBank. The most diverse virus, AP92, isolated from a
      tick in Greece, displayed the highest amino-acid difference (8.7%) with
      SPU415/85, isolated from a human infection in South Africa. Recombinant NP
      encoded for by codon-optimized S genes of SPU415/85 and AP92 were expressed in a
      bacterial host system and used to develop an in-house ELISA to detect IgG
      antibody against CCHFV in South African patients who survived infection. A total
      of 14/14 sera reacted with the South African recombinant NP and 13/14 reacted
      with the Greek recombinant NP. The serological cross-reactivity of the two NP
      antigens suggests that recombinant antigens prepared from geographically distinct
      CCHFV will have diagnostic and epidemiological applications worldwide.

PMID- 24330948
TI  - Dysfunctional Cognitions among Offspring of Individuals with Bipolar Disorder.
AB  - BACKGROUND: Individuals with bipolar disorder often endorse dysfunctional beliefs
      consistent with cognitive models of bipolar disorder (Beck, 1976; Mansell, 2007).
      AIMS: The present study sought to assess whether young adult offspring of those
      with bipolar disorder would also endorse these beliefs, independent of their own
      mood episode history. METHOD: Participants (N = 89) were young adult college
      students with a parent with bipolar disorder (n = 27), major depressive disorder
      (MDD; n = 30), or no mood disorder (n = 32). Semi-structured interviews of the
      offspring were used to assess diagnoses. Dysfunctional beliefs related to Beck
      and colleagues' (2006) and Mansell's (2007) cognitive models were assessed.
      RESULTS: Unlike offspring of parents with MDD or no mood disorder, those with a
      parent with bipolar disorder endorsed significantly more dysfunctional cognitions
      associated with extreme appraisal of mood states, even after controlling for
      their own mood diagnosis. Once affected by a bipolar or depressive disorder,
      offspring endorsed dysfunctional cognitions across measures. CONCLUSIONS:
      Dysfunctional cognitions, particularly those related to appraisals of mood states
      and their potential consequences, are evident in young adults with a parent who
      has bipolar disorder and may represent targets for psychotherapeutic
      intervention.

PMID- 24330949
TI  - Dietary L-arginine supplementation attenuates lipopolysaccharide-induced
      inflammatory response in broiler chickens.
AB  - In the present study, two experiments were conducted to investigate the effect of
      dietary L-arginine (Arg) supplementation on the inflammatory response and innate
      immunity of broiler chickens. Expt 1 was designed as a 2 * 3 factorial
      arrangement (n 8 cages/treatment; n 6 birds/cage) with three dietary Arg
      concentrations (1.05, 1.42 and 1.90%) and two immune treatments (injection of
      lipopolysaccharide (LPS) or saline) given at an interval of 48 h between 14 and
      21 d of age. In Expt 2, correlation between dietary Arg concentration (0.99,
      1.39, 1.76, 2.13 or 2.53%) and percentage of circulating B cells (percentage of
      circulating lymphocytes) was determined. In Expt 1, LPS injection decreased body
      weight gain and feed intake and increased feed conversion ratio of the challenged
      broilers (14-21 d; P< 0.05). LPS injection suppressed (P< 0.05) the percentages
      of splenic CD11+ and B cells (percentages of splenic lymphocytes) and phagocytic
      activity of splenic heterophils and macrophages; Arg supplementation linearly
      decreased the percentages of CD11+, CD14+ and B cells in the spleen (P< 0.10).
      LPS injection increased (P< 0.05) the expression of IL-1beta and IL-6 mRNA in the
      spleen and caecal tonsils. Arginine supplementation decreased (P< 0.05) the
      expression of IL-1beta, Toll-like receptor 4 (TLR4) and PPAR-gamma mRNA in the
      spleen and IL-1beta, IL-10, TLR4 and NF-kappaB mRNA in the caecal tonsils. In
      Expt 2, increasing dietary Arg concentrations linearly and quadratically reduced
      the percentage of circulating B cells (P< 0.01). Collectively, Arg
      supplementation attenuated the overexpression of pro-inflammatory cytokines
      probably through the suppression of the TLR4 pathway and CD14+ cell percentage.
      Furthermore, excessive Arg supplementation (1.76%) suppressed the percentages of
      circulating and splenic B cells.

PMID- 24330950
TI  - High prevalence of Toxoplasma gondii oocyst shedding in stray and pet cats (Felis
      catus) in Virginia, United States.
AB  - BACKGROUND: The protozoan Toxoplasma gondii is the causative agent of
      toxoplasmosis, with complications varying from mental disease to death. While
      human infection can occur via ingestion of tissue cysts from infected meat, most
      human infection comes from oocysts. Cats are the only definitive host, and thus
      shedding of oocysts by cats provides the ultimate source of toxoplasmosis.
      METHODS: While most studies in the area use seroprevalence to monitor Toxoplasma
      incidence in cat populations, this provides only a history of infection. This
      study used PCR detection of oocysts from cat feces to more accurately estimate
      the numbers of cats producing oocysts and thus posing an active health risk. DNA
      sequencing was use to confirm the identity of the PCR products. RESULTS: Of the
      49 cats tested, 9 yielded PCR products of the expected size. Six of the nine were
      determined by sequence analysis to be false positives, while three products were
      true positives. Overall, 6% of cats examined were found to be actively shedding
      oocysts. CONCLUSIONS: The incidence of oocyst shedding in the cat population
      studied was significantly higher than expected and higher than found in most cat
      populations world-wide. Of equal importance, the primers tested were shown to
      produce PCR products of multiple sizes and non-target products of expected size.
      We detected false positives at a higher rate than true positives, emphasizing the
      need for confirmatory analysis. Further research may produce better protocols for
      Toxoplasma detection from cat fecal samples.

PMID- 24330951
TI  - Life in acute mental health settings: experiences and perceptions of service
      users and nurses.
AB  - Background. Acute psychiatric provision in the UK today as well as globally has
      many critics including service users and nurses. Method. Four focus groups, each
      meeting twice, were held separately for service users and nurses. The analysis
      was not purely inductive but driven by concerns with the social position of
      marginalised groups - both patients and staff. Results. The main themes were
      nurse/patient interaction and coercion. Service users and nurses conceptualised
      these differently. Service users found nurses inaccessible and uncaring, whereas
      nurses also felt powerless because their working life was dominated by
      administration. Nurses saw coercive situations as a reasonable response to
      factors 'internal' to the patient whereas for service users they were driven to
      extreme behaviour by the environment of the ward and coercive interventions were
      unnecessary and heavy handed. Conclusion. This study sheds new light on living
      and working in acute mental health settings today by comparing the perceptions of
      service users and nurses and deploying service user and nurse researchers. The
      intention is to promote better practice by providing a window on the perceptions
      of both groups. 

PMID- 24330952
TI  - [Operative management of periampullary perforation complicated by ERCP].

PMID- 24330953
TI  - [Laparoscopic liver tumor resection of clinical experience in 126 patients].
AB  - OBJECTIVE: To explore the clinical application technology of completely
      laparoscopy hepodectomy (LH). METHODS: From June 2006 to December 2011, the 126
      cases of LH were performed, the data including operating time, blood loss and
      postoperative complications, etc, were analyzed retrospectively. The patients
      included 87 males and 39 female and they were 28-83 years old with an average age
      of 44.5 years old. The parenchyma was transected using laparoscopic ultrasonic
      scalpel and ligasure, accomplished with endoscopic linear stapler. Of all the
      patients, the diseases performed LH including primary liver carcinoma (45 cases),
      liver hemoangioma (58 cases), colon carcinoma with livermetastasis (23 cases),
      liver focar (5 cases), liver granuloma (1 case), liver adenoma (4 cases). The
      operations included left hemihepatectomy (n = 17), left lateral lobectomy (n =
      34), right hemihepatectomy (n = 15), segmentectomy (n = 22), local resection (n =
      59). RESULTS: Of all the patients, mean blood loss was 180 ml (10-1250 ml), mean
      surgical time was 142 minutes (43-220 minutes), mean postoperative hospital day
      was 2.2 days (3-12 days). Postoperative complications including eight cases of
      bile leakage, recovered after 1-3 weeks by appropriately draining. The patients
      with malignant tumor were followed up for 18 months (12-46 months), recurrence
      happened in 12 cases and four cases was died of recurrence and metastasis.
      CONCLUSIONS: LH is a safe, feasible and effective procedure for the treatment of
      benign liver disease and malignant liver neoplasm as long as the patient is
      properly selected, it should be recommended for radical resection of
      hepatocellular carcinoma.

PMID- 24330954
TI  - [The role of preoperative TACE on hepatocellular carcinoma located in caudate
      lobe].
AB  - OBJECTIVE: To evaluate the effect of preoperative transarterial chemoembolization
      (TACE) on hepatocellular carcinoma located in caudate lobe. METHODS: Totally 29
      cases of caudate lobe hepatocellular carcinoma admitted from January 2001 to
      December 2010 were analyzed retrospectively. Among the 29 patients, 23 were male
      and the other 6 were female. The median age was 52 years. According to receiving
      preoperative TACE or not, the 29 cases were divided into two groups: preoperative
      TACE plus surgery (group A, n = 11) and surgery only (group B, n = 18). The
      surgical results and long-term survival were compared between two groups.
      RESULTS: After TACE, the diameter of the tumour reduced by over 33.3% in 3
      patients, 10.0% to 33.3% in 6 patients, and less than 10.0% in 2 patients. The
      duration of surgery and intraoperative blood loss in group A were (298 +/- 39)
      minutes and (1031 +/- 310) ml, respectively. The duration of surgery and
      intraoperative blood loss in group B were (281 +/- 54) minutes and (868 +/- 403)
      ml, respectively. No significant difference was found in terms of these two
      groups (t = 1.006, P = 0.324; t = 1.223, P = 0.232). In addition, 6 cases in
      group A developed complications and 4 cases in group B did so. Only one patient
      died because of postoperative complication, and this patient belonged to group A.
      No significant difference was found between two groups (chi(2) = 0.028, P =
      0.868; chi(2) = 0.633, P = 0.426). The 5-year survival rate was 56.8% in group A
      and 34.9% in group B. The difference did not reach significant difference (P =
      0.132). CONCLUSIONS: For hepatocellular carcinoma located in caudate lobe,
      preoperative TACE does not significantly increase the surgical difficulty and
      impair the safety. In addition, preoperative TACE has the tendency to provide
      benefit to long-term survival.

PMID- 24330955
TI  - [The diagnosis and treatment of pancreatic neuroendocrine neoplasms].
AB  - OBJECTIVE: To analyze the prognostic factors of pancreatic neuroendocrine
      neoplasms (PNEN). METHODS: Clinical data of 61 patients with PNEN from March 1992
      to December 2012 was retrospectively analyzed. There were 23 male and 38 female
      patients, with a median age of 52 years (ranged from 22 to 68 years). Forty-one
      patients were non-functional tumors, and 20 patients were functional tumors.
      Fifty-nine patients received operation, 13 (22.0%) patients underwent
      laparoscopic operation, 2 patients underwent puncture biopsy under CT guidance.
      Survival was analyzed with the Kaplan-Meier method. RESULTS: Among these
      patients, 53 (86.9%) patients underwent curative resection. The cases of grade
      G1, G2, G3 were 41 (67.2%), 9 (14.8%), 11 (18.0%), respectively. The cases of
      stageI, II, III, IV were 47 (77.0%), 7 (11.5%), 2 (3.3%), 5 (8.2%), respectively.
      Liver metastasis, neural invasion were found in 5 cases (8.2%), 5 cases (8.2%),
      respectively. The median follow-up period was 40 months (ranged from 3 to 209
      months). The overall 1-, 3-, 5-year survival rates were 92.0%, 89.7%, 86.3%,
      respectively. Univariate analysis showed WHO classification (chi(2) = 18.503),
      TNM staging system (chi(2) = 23.401), liver metastasis (chi(2) = 18.606), neural
      invasion (chi(2) = 10.091), resection status (chi(2) = 25.514) were prognostic
      factors of PNEN (all P = 0.000). CONCLUSIONS: Surgical resection in PNEN results
      in long-term survival. WHO classification, TNM staging, resection status are
      effective in predicting the prognosis of PNEN. Liver metastasis, neural invasion
      predicted poor prognosis.

PMID- 24330956
TI  - [The clinic research of the modified laparoscopic splenectomy for massive
      splenomegaly in the treatment of children with hematologic diseases].
AB  - OBJECTIVE: To summarize the experience and characteristics of the modified
      laparoscopic splenectomy for massive splenomegaly in the treatment of children
      with hematologic disease. METHODS: The clinical data of 30 cases of laparoscopic
      splenectomy for massive splenomegaly of children with hematologic disease from
      March 2007 to December 2011 was analyzed retrospectively. There were 18 male and
      12 female patients, aging from 2 to 14 years. Primary disease included
      mediterranean anemia (17 cases), hereditary spherocytosis (4 cases) and
      idiopathic thrombocytopenic purpura (ITP, 9 cases). Dissection started with
      cutting off the gastrosplenic ligaments and lesser sac to fully reveal the
      splenic hilum, the splenic artery was clamped twice with 10 mm tiatanum clamp.
      When most of blood stored in the spleen back to heart through the veins and the
      splenic volume had already decreased, the splenic vein was ligated with 10 mm
      titanium clip and cut with ligsure and splenic pedicle separated. The Surgery and
      complication were recorded. For 1 week after surgery, the hemoglobin and platelet
      counts were reviewed. RESULTS: Twenty-six cases were performed successfully, and
      4 cases were converted to open procedure. Of the 4 cases, 2 cases was obesity
      because of idiopathic thrombocytopenic purpura, 1 case was beta thalassaemia
      combined severe liver enlargement, and 1 case was after partial splenic
      embolization. In cases of laparoscopic splenectomy, operation time was 110 to 130
      minutes, with an average of 120 minutes, and blood loss during operation was 35
      to 180 ml, with an average of 45 ml. Compared with pre-operation, the hemoglobin
      of mediterranean anemia and hereditary spherocytosis patients were (92 +/- 8)
      g/L, and blood platelet count of ITP patients was (127 +/- 20)*10(9)/L, and they
      increased obviously at 1 week after operation (t = 4.175 and 8.253, both P =
      0.000). CONCLUSION: The modified surgical method make the laparoscopic
      splenectomy for massive splenomegaly in many children with hematologic diseases
      possible, which was thought to be impossible in the past.

PMID- 24330957
TI  - [The surgical strategy for laparoscopic approach in recurrent inguinal hernia
      repair: 213 cases report].
AB  - OBJECTIVE: To evaluate the surgical strategy for laparoscopic approach in
      recurrent inguinal hernia repair. METHODS: Between January 2001 and December
      2011, the clinical data of 213 patients with 225 recurrent inguinal hernias
      underwent laparoscopic repair were retrospectively analyzed. There were 202 male
      and 11 female patients and their average age were (67 +/- 14) years old (range 22
      97 years old). The surgical methods included laparoscopic transabdominal
      preperitoneal hernia repair (TAPP, n = 174), total extraperitoneal herniorrhaphy
      (TEP, n = 41) and intraperitoneal onlay mesh (IPOM, n = 10). The follow-up period
      ranged from 15 to 60 months (median 42 months). No patient lost to follow-up
      during the investigation. RESULTS: The 48 TAPP and 26 TEP were applied to 77
      (32.9%) recurrent hernias after conventional suture repair; 23 TAPP and 15 TEP
      were utilized to 38 (16.9%) recurrent hernias after Lichtenstein repair; 90 TAPP
      and 1 IPOM were employed for 91 (40.4%) recurrent hernias after Patch and Plug
      repair; and the other 22 (9.8%) recurrent hernias after preperitoneal repair were
      repaired by using 13 TAPP and 9 IPOM techniques. No conversion to open surgery
      was observed. The average operative time was (39 +/- 14) minutes (range 15-90
      minutes). No patients required analgesia postoperatively. The postoperative
      average VAS score was 2.4 +/- 1.1 (range 1.2-6.4). The average hospital stay was
      (1.7 +/- 1.5) days (range 1-9 days), and the patients returned to unrestricted
      activities in 2 weeks was 99.6% (212 cases). No recurrence was observed during
      the follow-up. The accumulative postoperative complications rates was 11.1% (25
      cases), with 1 severe complication (surgical intervention was needed) as
      intraabdominal infection (0.4%), as well as other 24 complications including 15
      cases of seroma (6.7%), 5 cases of urinary retention (2.2%), 3 cases with
      transient paresthesia (1.3%) and 1 case with paralytic ileus (0.4%). CONCLUSIONS:
      TAPP and TEP are both feasible and efficacious techniques to treat recurrent
      hernias after suture repair and Lichtenstein repair, while the choice depends on
      surgeons' experience. Most recurrent hernias after Patch and Plug repair could be
      treated successfully by TAPP but TEP technique is not encouraged. For recurrences
      after preperitoneal repair, the TAPP repair should be recommended as first
      choice, while IPOM is a good technique to cope with the cases which TAPP failed.

PMID- 24330958
TI  - [Combined use of occluder plus bare stent in the treatment of aortic dissection
      with tear at the area of visceral branches].
AB  - OBJECTIVE: To evaluate the novel method of combinedly use of occluder and bare
      stent in the treatment of aortic dissection with distal tear at visceral
      branches. METHODS: From April 2010 to September 2012, 6 patients (5 male and 1
      female patients, aged from 29 to 62 years, mean 47.2 years) were diagnosed as
      Stanford type B aortic dissection that been revealed by CT angiography. The main
      tears were sealed with stent-grafts firstly, and then the tears at the visceral
      branch area were evaluated that impossible to close spontaneously. Atrium septal
      defect occluder and ventricular septal defect were implanted at the tears with
      the anterior disc in false lumen, while the posterior disc in the true lumen.
      After that, the bare stents were implanted in the true lumen to pull the
      occluders on the aortic wall. RESULTS: Among the 6 procedures, occluders were
      successfully implanted in 5 cases, and 1 failed anchoring at the tear, and the
      alternative method of coils embolization was applicated. After all the
      procedures, the immediate aortogrophy revealed that the false lumen disappeared
      in the 5 cases that occluders were used, and the visceral branches were all
      patent. No paraplegia, lesion of visceral organs or other complications occurred.
      All the cases were followed at least 5 months. There was one endoleak due to a
      non-sealed tear at the descending aorta, one new-occurred small tear in the
      descending aorta but with no communication to the false lumen. CONCLUSIONS: The
      combinedly use of occluder and bare stent in the treatment of aortic dissection
      with tears at the visceral branch area is a sum of two simple technique plus each
      other. It is easily to master. The lesions at the aortic that ordinary stent
      grafting incapable to seal are successfully solved then. The huge trauma of open
      or hybrid procedures are avoided.

PMID- 24330959
TI  - [Risk analysis for cerebral hyperperfusion syndrome after carotid
      endarterectomy].
AB  - OBJECTIVE: To analyze risk factors for cerebral hyperperfusion syndrome (CHS)
      after carotid endarterectomy (CEA). METHODS: From September 2010 to September
      2012, 183 consecutive patients with carotid artery stenosis who had indications
      for CEA entered the study. There were 149 male and 34 female patients, aged from
      38 to 83 years with an average of (66 +/- 9) years. Intracranial blood flow
      changes were monitored through transcranial Doppler routinely. Pre- and post
      operative middle cerebral artery velocity (VMCA) were recorded. CHS was diagnosed
      by the combination of hyperperfusion syndrome and 100% increase of VMCA after
      operation compared with pre-operative baseline values. The patients who had CHS
      during hospitalization were recorded. Pre-operative and operative related factors
      were analyzed by univariate analysis, followed by Logistic regression model, to
      identify the risk factors of CHS. RESULTS: Overall, CHS occurred in 15 patients
      (8.2%) after CEA. The average onset time was (2.6 +/- 0.2) days after surgery. By
      decreasing blood pressure and using dehydration medicine, all the patients with
      CHS recovered before discharge. None of them developed to intracranial
      hemorrhage. On univariate analysis, significant risk factors for CHS were history
      of stoke, symptomatic carotid artery stenosis and shunting during operation. On
      Logistic regression model, independent risk factor was symptomatic carotid artery
      stenosis (OR = 6.733, 95%CI: 1.455-31.155, P = 0.015), while shunting during
      operation (OR = 0.252, 95%CI: 0.067-0.945, P = 0.041) was a protective factor.
      CONCLUSIONS: Symptomatic carotid artery stenosis is an independent risk factor
      for CHS after CEA and shunting during operation is a protective factor. Using
      shunt may be an effective method of preventing CHS after CEA.

PMID- 24330960
TI  - [Cannulation related complications and prevention for extracorporeal membrane
      oxygenation: clinical report and reviews of experience of 34 cases].
AB  - OBJECTIVE: To review the cannulation strategies and associated vascular
      complications of extracorporeal membrane oxygenation (ECMO) and to investigate
      the etiology and preventive procedures for those complications. METHODS: From
      January 2007 to December 2011, 34 patients (21 male and 13 female patients, aged
      from 23 to 66 years) underwent ECMO support through open approach, semi-Seldinger
      method or full Seldinger method of cannulation. Bleeding and limb ischemia
      related to the approach as major complications were retrospectively analyzed.
      RESULTS: The ECMO duration were 2 to 21 days. Twenty-four patients (70.6%)
      successfully weaned from ECMO and 18 patients (52.9%) discharged. The
      venoarterial mode was used in 26 patients, and venovenous mode in 8 patients.
      Eight patients (30.8%, 6 for open approach and 2 for semi-seldinger) observed
      with limb ischemia, 2 of them required amputation, 1 had claudicatory sequela.
      Eleven and 6 patients suffered from bleeding and vessel injury respectively, all
      of them recovered by suitable treatment. CONCLUSIONS: The proper size of cannula,
      optimal approch and position adjustment, accurate cannula placement and carefully
      attendance are the key points to decrease the cannulation related complications.

PMID- 24330961
TI  - [A clinical study of preoperative prophylactic application of intra-aortic
      balloon pump in extreme high-risk patients undergoing coronary artery bypass
      grafting].
AB  - OBJECTIVE: To compare the clinical outcome between the intra-aortic balloon pump
      (IABP) inserted in the preoperative prophylactic condition and in the emergent
      condition for the patients with extreme high risks undergoing coronary artery
      bypass grafting (CABG). METHODS: Totally 92 extreme high risk patients undergoing
      CABG combined with IABP supporting, whose European System for Cardiac Operative
      Risk Evaluation were equal or more than 12 points, some also undergoing surgical
      operations of myocardial infarction mechanical complications from January 2008 to
      June 2011, were analyzed retrospectively. According to the IABP established time,
      these patients were divided into two groups: preoperative group (57 cases) and
      passive group (35 cases). Items of comparison between two groups were the rate of
      mortality, myocardial infarction rate, severity of postoperative myocardial
      dysfunction and inotropic drug consumption quantity, IABP support time,
      respiratory support time, ICU stay time, renal function and IABP related
      complications. RESULTS: Perioperative mortality and myocardial infarction rate in
      preoperative group (1.8%, 3.5%) were significant lower than those in passive
      group (11.4%, 17.1%) (chi(2) = 3.949, P = 0.047; chi(2) = 5.077, P = 0.024).
      Compared to passive group, the IABP support time, respiratory support time, and
      ICU stay time (t = 4.113-4.795); severity of postoperative myocardial dysfunction
      and inotropic drug consumption quantity, and renal dysfunction (chi(2) = 5.077
      23.521) were decreased significantly in preoperative group (all P < 0.05). There
      were no significant difference in IABP related complications (P = 0.431).
      CONCLUSIONS: For extreme high risk CABG patients, comparing to passive insertion
      of the IABP, preoperative prophylactic application of IABP shows the advantages
      in reducing perioperative mortality, myocardial infarction rate, inotropic drug
      consumption quantity, renal dysfunction, ICU stay time, respiratory support time
      and IABP support time.

PMID- 24330962
TI  - [Airway management and use of miniature extracorporeal circulation in tracheal
      surgery: a single center experience].
AB  - OBJECTIVE: To review the methods involved in airway management of tracheal
      surgery and to consider the role of extracorporeal circulation. METHODS: A total
      of 91 tracheal surgeries were performed from January 2008 to February 2012,
      including 60 cases of tumor, 8 cases of post-traumatic stenosis and 23 cases of
      post-tracheostomy stenosis. There were 76 male and 15 female patients, aged from
      4 to 77 years. Anesthetic plans were made according to the severity and position
      of stenosis. Rapid sequent induction intubations were conducted on 56 patients,
      tracheostomy intubations on 25 patients, awake intubations on 3 patients,
      extracorporeal circulation on 6 patients and emergent sternotmy and tracheostomy
      on 1 patient. Miniature extracorporeal circulation systems were used in all
      extracorporeal circulation case. RESULTS: All patients discharged without major
      complications. There were 2 cases of massive bleeding during operations, 1 case
      of post-operative tracheal fistula and 1 case of post-operative incision
      infection. All these 4 cases were treated properly and got cured. One patient on
      whom extracorporeal circulation was unable to set up underwent 6 minutes of
      hypoxia before sterotomy and tracheostomy. All the extracorporeal circulation
      cases were hemodynamically stable during bypass and none of them need massive
      transfusion. The miniature extracorporeal circulation system was convenient to
      use and especially suitable for tracheal surgery. CONCLUSIONS: Various advanced
      anesthesia techniques can ensure a safe airway for most tracheal surgeries.
      However, extracorporeal circulation plays a major role in high risk cases. It is
      important to set up a miniature extracorporeal circulation circuit that is
      especially suitable for tracheal surgery.

PMID- 24330963
TI  - [The efficacy analysis of selective decompression of lumbar root canal of elderly
      lumbar spinal stenosis].
AB  - OBJECTIVE: To evaluate the effect of the treatments of lumbar spinal stenosis by
      selective decompression of lumbar root canal and laminectomy. METHODS: From March
      2007 to March 2011, 144 lumbar spinal stenosis patients were treated by selective
      decompression of lumbosacral root canal and laminectomy. All of these patients
      included 64 male and 80 female patients, age range 60-87 years, average (66 +/-
      5) years. Duration 6-72 months, average (12 +/- 16) months. The patients were
      divided into 2 groups according to surgical procedure underwent: group A
      including 70 patients who were treated with selective decompression of lumbar
      root canal, group B including 74 patients who were treated with traditional
      laminectomy. Five time points were selected to assess clinical effect using
      Oswestry disability index (ODI) and Japanese Orthopaedic Association (JOA), which
      were pre-operation and 1 month, 6 months, 12 months and last follow-up. The data
      were analyzed through Wilcoxon matched-pairs signed-ranks test. RESULTS: All
      operations were completed well without severe complications. The duration of
      follow-up was 12-55 months, average (31 +/- 6) months. All patients' symptoms got
      improved or partial remission. The average pre- and post-operative scores of JOA
      in group A and B were from 14.0 +/- 1.6 to 20.3 +/- 1.7, from 13.6 +/- 1.7 to
      20.2 +/- 2.0, respectively, there were significant statistical differences (Z =
      2.41 and 2.23, P < 0.05). The average pre- and post-operative scores of ODI in
      group A and B were from 62% +/- 4% to 28% +/- 4%, from 63% +/- 4% to 27% +/- 3%,
      respectively, there were significant statistical differences (Z = 2.93 and 2.64,
      P < 0.05). CONCLUSIONS: Personalized treatment programs should be established for
      elderly lumbar spinal stenosis according to stenosis location. Laminectomy is
      carried out with the stenosis in the central spinal canal; selective
      decompression of lumbosacral root canal is accepted with the stenosis in the
      nerve root canal without central stenosis.

PMID- 24330964
TI  - [Analysis of clinical results and complications of growing rod technique for
      congenital scoliosis].
AB  - OBJECTIVE: To evaluate clinical outcomes of growing rod technique in treating
      young children with congenital scoliosis. METHODS: From August 2002 to October
      2009, 34 patients with congenital scoliosis underwent growing rod procedures
      including 12 male and 22 female patients. Four patients underwent posterior
      correction surgeries with single growing rod (single growing rod group), 30
      patients underwent posterior correction surgeries with dual growing rod(dual
      growing rod group). The average age at initial surgery was 6.9(2-13) years. Five
      patients with severe rigid deformity or kyphosis had an osteotomy at apex
      vertebra with short segmental fusion followed by dual growing rod technique. The
      analysis included age at initial surgery and final fusion (if applicable), number
      and frequency of lengthenings, and complications. Radiographic evaluation
      including scoliosis, trunk translation, length of T1-S1, thoracic kyphosis and
      lumbar lordosis was conducted. RESULTS: The follow-up was 40.5 (24-110) months.
      In single growing rod group, the mean scoliosis Cobb angle improved from 80.9
      degrees to 59.5 degrees after initial surgery and was 65.3 degrees at the latest
      follow-up. T1-S1 length increased from average 24.3 cm to 26.0 cm after initial
      surgery, and to 31.1 cm at latest follow-up with an increase of 1.05 cm per year.
      The space available for lung ratio(SAL) in patients with thoracic curves improved
      from 0.81 to 0.92 at the latest follow-up. Three patients reached final fusion.
      Four complications occurred in 3 of the 4 patients. In dual growing rod group,
      the mean scoliosis Cobb angle improved from 72 degrees  +/- 22 degrees to 35 +/-
      14 degrees  after initial surgery and was 35 +/- 17 degrees at the last follow-up
      or post-final fusion. T1-S1 length increased from (25 +/- 5) cm to (29 +/- 5)cm
      after initial surgery and to (33 +/- 5)cm at latest follow-up with an average T1
      S1 length increase of 1.49 cm per year. The SAL in patients with thoracic curves
      improved from 0.84 +/- 0.08 to 0.96 +/- 0.06 at the latest follow-up. Three
      patients reached final fusion. Complications occurred in 7 of the 30 patients,
      and they had a total of 13 complications. CONCLUSIONS: Growing rod technique is a
      safe and effective choice for young children of long, complex congenital
      scoliosis. It maintains correction achieved at initial surgery while allowing
      spinal growth to continue. Implants-related complications remain the biggest
      challenge.

PMID- 24330965
TI  - [Diagnosis and treatment of giant cell tumor of bone in skeletal immature
      patients].
AB  - OBJECTIVE: To demonstrate the common characteristics of giant cell tumor of bone
      in immature skeletons. METHODS: From 1989 to 2009, the 8 skeletal immature
      patients were pathologically diagnosed with giant cell tumor (GCT) in our
      department, which accounted for 1.3% (8/621) of all GCT patients in an extremity.
      All patients were identified with an open epiphyseal plate by retrospective
      review of the radiograph, CT or MRI by senior consultants. Oncological and
      functional outcome were followed for a mean 44.1 months. There were 5 boys and 3
      girls. The mean age was 13.8 years. All cases had a primary lesion. The distal
      femur is the most common site involved (3 cases), followed by the proximal tibia
      (2 cases). The proximal humerus, the distal tibia and the distal radius accounted
      for 1 case respectively. Oncological and functional outcome are followed for a
      mean 44.1 months. RESULTS: All lesions were lytic. Six lesions involved both the
      epiphysis and metaphysis. Two lesions located in the metaphysis area. Six lesions
      were treated with extended curettage and were reconstructed with allograft and
      (or) bone cement. Internal fixations were used in 2 cases. Two cases were treated
      with segmental resection. And one was reconstructed with cement spacer and the
      other one with segmental allograft and internal fixation. One patient (1/6)
      developed a bone recurrence after extended curettage. No extremity deformity and
      discrepancy were found during the follow up after the curettage. No metastasis
      was found during the follow up. CONCLUSION: Histologically GCT occurs in skeletal
      immature bone has the same pathological appearance but radiologically has its
      unique features. These lesions share same behavior as that in adults. A low local
      recurrence rate and good function can be achieved after a proper surgery.

PMID- 24330966
TI  - [The effects of gastric bypass procedures on blood glucose, gastric inhibitory
      polypeptide and glucagon-like peptide-1 of normal glucose tolerance dogs].
AB  - OBJECTIVE: To observe postoperative glucose tolerance, gastric inhibitory
      polypeptide (GIP) , and glucogan-like peptide-1 (GLP-1) in normal glucose level
      dogs after undergoing gastric bypass procedures, and to explore the mechanism of
      gastric bypass procedures to treat type 2 diabetes. METHODS: The 6 dogs with
      normal glucose tolerance had undergone gastric bypass procedures, and measure
      preoperative and postoperative oral and intravenous glucose tolerance (at time
      points 1, 2, and 4 weeks) through changes in blood glucose, insulin, gastric
      inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and measure
      preoperative and postoperative week 4 pancreatic tissue morphology. RESULTS:
      Second weeks after operation, the fasting blood sugar was (3.58 +/- 0.33) mmol/L,
      and significantly lower than preoperative (t = 3.571, P < 0.05). The GLP-1 level
      before oral glucose tolerance test (OGTT) and 30 minutes after OGTT were (0.90 +/
      0.21) and (0.91 +/- 0.19) pmol/L respectively, and significantly higher than
      preoperative (t value were -3.660 and -2.971, P < 0.05). GLP-1 levels began to
      decrease in the second week after surgery. After 4 weeks, the index recovered to
      the preoperative level. Four weeks after surgery when compared with preoperative,
      islet morphology, islet number (6.8 +/- 0.8 and 7.1 +/- 0.8 respectively) and
      islet cells (16.7 +/- 2.5 and 16.3 +/- 3.1 respectively) did not change
      significantly (P > 0.05). CONCLUSION: Gastric bypass procedures could be briefly
      affect normal glucose tolerance in dogs' blood glucose, insulin and diabetes
      related gastrointestinal hormones.

PMID- 24330967
TI  - [Regulation effect of adipose-derived mesenchymal stem cells on pancreatic cancer
      cells].
AB  - OBJECTIVE: To analyze the effects of adipose tissue-derived stem cells (ADSCs) on
      the proliferation and invasion of pancreatic cancer (PaCa) cells and the the
      possible mechanism involved. METHODS: ADSCs were isolated and co-cultured with
      PaCa cells. CCK-8 assay was used to detect the proliferation of PaCa cells. An
      ELISA was used to determine the concentration of stromal cell-derived factor-1
      (SDF-1) in the supernatants. The proliferation of PaCa cells by SDF-1 was
      measured. AMD3100 regulated the co-culture of ADSCs and PaCa. The tumor growth of
      PaCa cells was assessed after treatment by ADSCs in vivo. RESULTS: ADSCs can
      promote the proliferation and invasion of PaCa cells (proliferation: SW1990:
      1.535 +/- 0.153; PANC-1: 1.370 +/- 0.100; the value of control was 1; invasion:
      SW1990: 47.0 +/- 2.6 vs. 28.3 +/- 1.3; PANC-1: 40.3 +/- 1.8 vs. 24.3 +/- 1.3; t =
      4.332-9.558, P < 0.05). The expression of SDF-1 was high in ADSCs, but not in
      PaCa cells (69 +/- 5 vs. 0 and 0, F = 389.134, P < 0.01). The promotion of SDF-1
      on PaCa cells depends on the concentration. AMD3100 significantly downregulates
      these growth-promoting effects of ADSCs on PaCa cells. ADSCs significantly
      promoted the growth of SW1990 in nude mice at the 5(th) week (volume: (1295 +/-
      102) mm(3) vs. (967 +/- 81) mm(3), t = 5.614, P < 0.05) , but not in PANC-1 cell.
      CONCLUSION: ADSCs can promote the proliferation and invasion of PaCa cells, which
      may involve the SDF-1/CXCR4 axis.

PMID- 24330969
TI  - [The great virus comeback].
AB  - Viruses have been considered for a long time as by-products of biological
      evolution. This view is changing now as a result of several recent discoveries.
      Viral ecologists have shown that viral particles are the most abundant biological
      entities on our planet, whereas metagenomic analyses have revealed an unexpected
      abundance and diversity of viral genes in the biosphere. Comparative genomics
      have highlighted the uniqueness of viral sequences, in contradiction with the
      traditional view of viruses as pickpockets of cellular genes. On the contrary,
      cellular genomes, especially eukaryotic ones, turned out to be full of genes
      derived from viruses or related elements (plasmids, transposons, retroelements
      and so on). The discovery of unusual viruses infecting archaea has shown that the
      viral world is much more diverse than previously thought, ruining the traditional
      dichotomy between bacteriophages and viruses. Finally, the discovery of giant
      viruses has blurred the traditional image of viruses as small entities.
      Furthermore, essential clues on virus history have been obtained in the last ten
      years. In particular, structural analyses of capsid proteins have uncovered
      deeply rooted homologies between viruses infecting different cellular domains,
      suggesting that viruses originated before the last universal common ancestor
      (LUCA). These studies have shown that several lineages of viruses originated
      independently, i.e., viruses are polyphyletic. From the time of LUCA, viruses
      have coevolved with their hosts, and viral lineages can be viewed as lianas
      wrapping around the trunk, branches and leaves of the tree of life. Although
      viruses are very diverse, with genomes encoding from one to more than one
      thousand proteins, they can all be simply defined as organisms producing virions.
      Virions themselves can be defined as infectious particles made of at least one
      protein associated with the viral nucleic acid, endowed with the capability to
      protect the viral genome and ensure its delivery to the infected cell. These
      definitions, which clearly distinguish viruses from plasmids, suggest that
      infectious RNA molecules that only encode an RNA replicase presently classified
      among viruses by the ICTV (International Committee for the Taxonomy of Viruses)
      into families of Endornaviridae and Hypoviridae are in fact RNA plasmids. Since a
      viral genome should encode for at least one structural protein, these definitions
      also imply that viruses originated after the emergence of the ribosome in an RNA
      protein cellular world. Although virions are the hallmarks of viruses, viruses
      and virions should not be confused. The infection transforms the ribocell (cell
      encoding ribosomes and dividing by binary fission) into a virocell (cell
      producing virions) or ribovirocell (cell that produces virions but can still
      divide by binary fission). In the ribovirocell, two different organisms, defined
      by their distinct evolutionary histories, coexist in symbiosis in the same cell.
      The virocells or ribovirocells are the living forms of the virus, which can be in
      fine considered to be a living organism. In the virocell, the metabolism is
      reorganized for the production of virions, while the ability to capture and store
      free energy is retained, as in other cellular organisms. In the virocell, viral
      genomes replicate, recombine and evolve, leading to the emergence of new viral
      proteins and potentially novel functions. Some of these new functions can be
      later on transferred to the cell, explaining how viruses can play a major (often
      underestimated) role in the evolution of cellular organisms. The virocell concept
      thus helps to understand recent hypotheses suggesting that viruses played a
      critical role in major evolutionary transitions, such as the origin of DNA
      genomes or else the origin of the eukaryotic nucleus. Finally, it is more and
      more recognized that viruses are the major source of variation and selection in
      living organisms (both viruses and cells), the two pillars of darwinism. One can
      thus conclude that the continuous interaction between viruses and cells, all
      along the history of life, has been, and still is, a major engine of biological
      evolution. 

PMID- 24330970
TI  - [Enigmatic archaeal viruses].
AB  - Viruses infecting microorganisms of the third domain of life, Archaea, are still
      poorly characterized: to date, only about fifty of these viruses have been
      isolated. Their hosts are hyperthermophilic, acidothermophilic, and extreme
      halophilic or methanogenic archaea. Their morphotypes are highly diverse and
      their gene content is very specific. Some of these viruses have developed
      extraordinary mechanisms to open the cell wall thanks to the formation of
      exceptional pyramidal nanostructures. The still limited knowledge about the
      biology of archaeoviruses should develop rapidly in the coming years. 

PMID- 24330971
TI  - [Phagotherapy: a nightmare for bacteria, a dream for physicians?].
AB  - Bacteriophages were discovered in the early 20th century and rapidly used to
      treat bacterial infections in humans. As the first specific antibacterial agents,
      they were used worldwide until antibiotics ramped up. Thereafter, rapidly
      forgotten, they became the favorite toolbox for researchers that used them to
      elucidate some of the most fundamental aspects of the cellular life at the
      molecular level. Today, facing the threat of antibiotic resistant bacteria,
      bacteriophages are being reconsidered for their use in medicine. During the past
      century, knowledge on bacteriophages has improved considerably, nevertheless
      phage therapy is still in its infancy. Taking two examples of recently published
      experimental phage therapy results, this article summarizes the hopes but also
      the challenges that surround the future development of human phage therapy. 

PMID- 24330972
TI  - [G protein-coupled receptors in the spot light].
AB  - G protein-coupled receptors (GPCRs), also known as seven transmembrane domain
      spanning proteins (7TM), play an important role in tissue homeostasis and
      cellular and hormonal communication. GPCRs are targeted by a large panel of
      natural ligands such as photons, ions, metabolites, lipids and proteins but also
      by numerous drugs. Research efforts in the GPCR field have been rewarded in 2012
      by the Nobel Price in Chemistry. The present article briefly summarizes our
      current knowledge on GPCRs and discusses future challenges in terms of
      fundamental aspects and therapeutic applications. 

PMID- 24330973
TI  - [Pluripotency and induced nuclear reprogramming in vertebrates: new
      perspectives].
AB  - Pluripotency is a transitory state during vertebrate development. A pluripotent
      cell can theoretically acquire all cell fates of the organism. During ontogenetic
      dynamics, loss of pluripotency is associated with a progressive acquisition of a
      specific genetic program, which is determined both by instructions received and
      by cell position in the whole organism. Pluripotent embryonic stem cells can be
      isolated and cultured in vitro indefinitely. Using mammalian embryonic stem cells
      (ESCs), it has been possible to identify the factors involved in the
      establishment and maintenance of pluripotency state. In this review, we will
      describe recent scientific advances in the understanding of pluripotency, the
      molecular actors involved in such a regulation and their functional conservation
      during evolution. We shall focus on new concepts, obtained from the study of
      vertebrate model organisms, to shed light on the cell transition from
      pluripotency to differentiated state, and shall recapitulate fundamental and
      clinical applications of pluripotent cells, of "somatic cell nuclear transfer"
      (SCNT), of induced nuclear reprogramming in vitro and future perspectives of in
      vivo applications. Our results, in the xenopus, concerning the first in vivo
      induced nuclear reprogramming might open new perspectives about the understanding
      of cell plasticity in an integrated context. Our analyses sought to encourage new
      and alternative clinical approaches to achieve in situ tissue regeneration. 

PMID- 24330974
TI  - [Introduction].

PMID- 24330975
TI  - [Cardiovascular diseases in Spain: conclusions and final comments].

PMID- 24330976
TI  - Human migration is important in the international spread of exotic Salmonella
      serovars in animal and human populations.
AB  - The exposure of indigenous humans and native fauna in Australia and the Wallacea
      zoogeographical region of Indonesia to exotic Salmonella serovars commenced
      during the colonial period and has accelerated with urbanization and
      international travel. In this study, the distribution and prevalence of exotic
      Salmonella serovars are mapped to assess the extent to which introduced
      infections are invading native wildlife in areas of high natural biodiversity
      under threat from expanding human activity. The major exotic Salmonella serovars,
      Bovismorbificans, Derby, Javiana, Newport, Panama, Saintpaul and Typhimurium,
      isolated from wildlife on populated coastal islands in southern temperate areas
      of Western Australia, were mostly absent from reptiles and native mammals in less
      populated tropical areas of the state. They were also not recorded on the
      uninhabited Mitchell Plateau or islands of the Bonaparte Archipelago, adjacent to
      south-eastern Indonesia. Exotic serovars were, however, isolated in wildlife on
      14/17 islands sampled in the Wallacea region of Indonesia and several islands off
      the west coast of Perth. Increases in international tourism, involving islands
      such as Bali, have resulted in the isolation of a high proportion of exotic
      serovar infections suggesting that densely populated island resorts in the Asian
      region are acting as staging posts for the interchange of Salmonella infections
      between tropical and temperate regions.

PMID- 24330977
TI  - Prognostic factors in young women with cutaneous melanoma.
AB  - BACKGROUND: Gender is an established prognostic factor in cutaneous melanoma;
      women as a group have a better overall prognosis than men. However, the
      investigators hypothesized that melanoma in young women may have distinct
      clinicopathologic features and biologic behavior compared with melanoma in older
      women, possibly related to tanning bed use and excessive acute episodes of sun
      exposure. METHODS: A retrospective analysis was performed of a large multicenter
      study that accrued patients between 1996 and 2003 and included patients aged 18
      to 70 years with cutaneous melanoma >=1 mm Breslow thickness and no evidence of
      regional or distant metastatic disease. All women with follow-up data were
      included. Univariate and multivariate analyses as well as Kaplan-Meier (KM)
      analysis were performed to test for differences in clinicopathologic variables,
      disease-free survival (DFS), and overall survival (OS) between female patients
      <=40 and >40 years of age. RESULTS: A total of 1,056 female patients were divided
      into 2 groups: those >40 years of age (n = 757 [71.7%]) and those <=40 years of
      age (n = 299 [28.3%]). Overall, there were no differences in Breslow thickness,
      ulceration, or sentinel lymph node status between groups. Compared with older
      women, younger women were more likely to have truncal melanomas (39.5% vs 29.5%,
      P = .0017) and less likely to have regression of the primary tumor (6.4% vs
      11.5%, P = .0208). The mean number of sentinel lymph nodes removed was 2.82 for
      younger women and 2.29 for older women (P < .0001). Multivariate analysis
      revealed that Breslow thickness, ulceration, and tumor-positive sentinel lymph
      node were associated with worse DFS in both the younger and older groups; truncal
      location was associated with worse DFS in the younger group only. The same
      factors were predictive of OS in both groups, except that ulceration was not
      significant in the younger patient group. In the younger patient group, the 5
      year KM DFS rates were 78.1% for truncal melanomas and 92.5% for nontruncal
      melanoma locations (P = .0009); the corresponding 5-year KM OS rates were 76.6%
      and 93.9% (P = .0003). In the older patient group, the 5-year KM DFS rates were
      84.1% for truncal and 82.8% for nontruncal melanomas (P = NS), and the
      corresponding 5-year KM OS rates were 81.6% and 87.5% (P = .0049). CONCLUSIONS:
      Although women with cutaneous melanoma tend to have a better prognosis than men,
      women <=40 years of age with primary melanoma of the trunk may represent a
      subgroup at higher risk for disease recurrence and metastasis.

PMID- 24330980
TI  - [Knowledge about genotype-phenotype of the diseases should be coming into
      pediatrician's horizon].

PMID- 24330979
TI  - A Qualitative Investigation of Therapists' Attitudes towards Research: Horses for
      Courses?
AB  - BACKGROUND: A large body of research has identified that many therapists do not
      use research to inform their practice, but few studies investigate the reasons
      behind this. AIMS: The current study seeks to understand what sources therapists
      use to inform their practice and why they are chosen. METHOD: Thirty-three
      interviews with psychological therapists in the UK were undertaken. These were
      transcribed and analysed using Interpretative Phenomenological Analysis. RESULTS:
      Two superordinate themes emerged. The former focused on the nature of evidence
      and the latter described why certain sources were used to make clinical
      decisions. When discussing evidence, participants felt that research studies,
      specifically Randomized Controlled Trials (RCTs), used unrepresentative samples.
      Therapists felt that research other than RCTs, particularly qualitative research,
      was important. Therapist specific factors were felt to be as, or more, important
      than the technique used to treat patients. When discussing the sources they used,
      therapists preferred to use their clinical experience or their patients'
      experience to make clinical decisions. Theoretical or practical information was
      preferred to empirical research. The presentation of information was felt to be
      important to encourage the implementation of research, and therapists also felt
      tools such as outcome measures and manuals were too rigid to be useful. Finally,
      patients' choice of treatment was felt to be important in treatment decisions.
      CONCLUSIONS: The views of therapists were heterogeneous, but this study
      highlighted some of the barriers to closing the gap between science and practice.
      This knowledge can be used to increase the translation of science into practice.

PMID- 24330978
TI  - Molecular evidence for historical presence of knock-down resistance in Anopheles
      albimanus, a key malaria vector in Latin America.
AB  - BACKGROUND: Anopheles albimanus is a key malaria vector in the northern
      neotropics. Current vector control measures in the region are based on mass
      distributions of long-lasting insecticidal nets (LLINs) and focal indoor residual
      spraying (IRS) with pyrethroids. Resistance to pyrethroid insecticides can be
      mediated by increased esterase and/or multi-function oxidase activity and/or
      mutations in the voltage-gated sodium channel gene. The aim of this work was to
      characterize the homologous kdr region of the voltage-gated sodium channel gene
      in An. albimanus and to conduct a preliminary retrospective analysis of field
      samples collected in the 1990's, coinciding with a time of intense pyrethroid
      application related to agricultural and public health insect control in the
      region. METHODS: Degenerate primers were designed to amplify the homologous kdr
      region in a pyrethroid-susceptible laboratory strain (Sanarate) of An. albimanus.
      Subsequently, a more specific primer pair was used to amplify and sequence the
      region that contains the 1014 codon associated with pyrethroid resistance in
      other Anopheles spp. (L1014F, L1014S or L1014C). RESULTS: Direct sequencing of
      the PCR products confirmed the presence of the susceptible kdr allele in the
      Sanarate strain (L1014) and the presence of homozygous-resistant kdr alleles in
      field-collected individuals from Mexico (L1014F), Nicaragua (L1014C) and Costa
      Rica (L1014C). CONCLUSIONS: For the first time, the kdr region in An. albimanus
      is described. Furthermore, molecular evidence suggests the presence of kdr-type
      resistance in field-collected An. albimanus in Mesoamerica in the 1990s. Further
      research is needed to conclusively determine an association between the genotypes
      and resistant phenotypes, and to what extent they may compromise current vector
      control efforts.

PMID- 24330981
TI  - [Lung ultrasound for diagnosis of neonatal atelectasis].
AB  - OBJECTIVE: The diagnosis of neonatal atelectasis (NA) is usually based on
      clinical manifestations and chest X-rays, lung ultrasounds are not included in
      the diagnostic work-up of NA.Recently, ultrasounds have been used extensively and
      successfully in the diagnosis of many kinds of lung diseases, but few studies
      have addressed NA. The aim of this study was to evaluate the ultrasound imaging
      features of NA-and to evaluate the value of lung ultrasound in diagnosing NA.
      METHOD: From May, 2012 to June, 2013, 40 newborn infants with NA and another 40
      neonates without lung disease were enrolled into this study.Lung ultrasound was
      performed at the bedside by a single expert physician.In a quiet state, the
      infants were positioned in supine, side or prone postures. The lung field was
      divided into three areas by the anterior auxilary and posterior auxilary line.
      The regions of the bilateral lungs were scanned by the probe which was vertical
      or parallel with the ribs, then compared the results with conventional chest X
      ray findings. RESULT: (1) The main ultrasound imaging features of neonatal NA
      include lung consolidation with air bronchograms, pleural line abnormalities and
      A-line disappearance. Besides, lung pulse and lung sliding disappearance could be
      seen by real-time ultrasound. (2) The sensitivity of lung ultrasound for
      diagnosis of NA was 100%, while it was only 70% for conventional chest X-rays.
      CONCLUSION: Use of ultrasound to diagnose NA is accurate and reliable, the
      sensitivity was superior to that of conventional chest X-ray examination, which
      also has many other advantages including easy-operating, non-ionizing, can be
      performed at the bedside, therefore, ultrasonic can provide important value for
      clinicians.

PMID- 24330982
TI  - [Changes of the hemodynamics and extravascular lung water after different-volume
      fluid resuscitation in a piglet model of endotoxic shock].
AB  - OBJECTIVE: Practice recommendations have evolved, and consensus now exists among
      leading organizations such as the American College of Critical Care Medicine
      (ACCM) and Surviving Sepsis Campaign that fluid infusion is best initiated with
      boluses of 20 ml/kg, commonly requires 40-60 ml/kg but can be as much as 200
      ml/kg if the liver is not enlarged and/or rales are not heard. The present study
      aimed to investigate and compare the changes of the hemodynamics and
      extravascular lung water after higher volume fluid resuscitation in a piglet
      model of endotoxic shock. METHOD: Twenty piglets were used for establishing
      animal models of endotoxic shock by intravenous infusing lipopolysaccharide
      (LPS). The experimental animals were divided into three groups according to the
      volume infused during the resuscitation. The three groups received different
      volume of saline in less than an hour after endotoxic shock. By the PiCCO plus
      system, we investigated the changes of hemodynamics and extravascular lung water.
      RESULT: After fluid resuscitation, global end diastolic volume inder, (GEDI) and
      intrathoracic blood volume index, (ITBI) markedly increased in the group of 80
      ml/kg and 120 ml/kg, but there was no change in the group of 40 ml/kg. GEDI:
      Fifteen min after fluid resuscitation R1 was (261 +/- 64) ml/m(2), R2 (457 +/-
      124) ml/m(2), R3 (413 +/- 148) ml/m(2), 4 h R1 (251 +/- 68) ml/m(2), R2 (422 +/-
      70) ml/m(2), R3 (470 +/- 160) ml/m(2); ITBI: Fifteen min after fluid
      resuscitation R1 was (335 +/- 69) ml/m(2), R2 (550 +/- 179) ml/m(2), R3 (520 +/-
      183) ml/m(2), 4 h R1 (314 +/- 84) ml/m(2), R2 (534 +/- 96) ml/m(2), R3 (594 +/-
      200) ml/m(2) (R1 vs. R2 vs. R3, F = 26.373, P < 0.05; R1 vs. R2, R1 vs. R3, P <
      0.05; R2 vs. R3, P > 0.05). CI of all three groups significantly decreased when
      the models were established. After fluid resuscitation, the base level was
      maintained in the group of 80 ml/kg and 120 ml/kg, but it was under the basic
      level in the group of 40 ml/kg.Fifteen min after fluid resuscitation R1 was (4.5
      +/- 0.7) L/(min.m(2)), R2 (6.4 +/- 2.2) L/(min.m(2)), R3 (5.5 +/- 0.7)
      L/(min.m(2)), 4 h R1 (4.1 +/- 1.0) L/(min.m(2)), R2 (5.2 +/- 0.9) L/(min.m(2)),
      R3 (5.1 +/- 0.8) L/(min.m(2)). There was no significant difference in CI between
      these two groups (P > 0.05).ELWI of the group of 80 ml/kg and 120 ml/kg were
      still higher than that of the group of 40 ml/kg, 15 min after fluid resuscitation
      R1 was (19.2 +/- 8.6) ml/kg, R2 (29.2 +/- 5.5) ml/kg, R3 (23.4 +/- 8.2) ml/kg, 4
      h R1 (18.3 +/- 6.5) ml/kg, R2 (23.8 +/- 2.6) ml/kg, R3 (21.4 +/- 3.9) ml/kg, but
      there was no significant difference in ELWI among the groups (P > 0.05).
      CONCLUSION: Resuscitation with higher volume of fluid infusion in the early stage
      of endotoxic shock was more efficient to increase the preload and maintain the
      cardiac output at the baseline level, and might reduce the need for vasoactive
      agents. Meanwhile, resuscitation with higher volume of fluid in the early stage
      of endotoxic shock did not sharply increase the extravascular lung water.

PMID- 24330983
TI  - [Effects of different types and concentration of oral sweet solution on reducing
      neonatal pain during heel lance procedures].
AB  - OBJECTIVE: To compare the effect of different types and concentrations of sweet
      solutions on neonatal pain during heel lance procedure. METHOD: Totally 560 full
      term neonates (male 295, female 265) were randomized into 7 groups:placebo group
      (plain water), 10% glucose, 25% glucose, 50% glucose, 12% sucrose, 24% sucrose
      and 30% sucrose groups.In each group, 2 ml corresponding oral solutions were
      administered through a syringe by dripping into the neonate's mouth 2 minute
      before heel lance. The procedure process was recorded by videos, from which to
      collect heart rate, oxygen saturation and pain score 1 min before puncture, 3, 5
      and 10 min after puncture. RESULT: The average heart rate increase 3, 5 and 10
      min after procedure in the 25% and 50% glucose groups, 12% and 24% and 30%
      sucrose groups was significantly lower than those in the placebo group (P < 0.01
      or 0.05). The average heart rate increase 3 min after procedure in the sucrose
      group was lower than that in the glucose group (P < 0.01).Neonates who received
      30% sucrose has a significantly lower average heart rate increase than those who
      received 12% and 24% sucrose 3 min after heel lance (both P < 0.05) . The average
      oxygen saturation decrease 3, 5, 10 min after procedure was significantly lower
      than those in the placebo group (P < 0.01). The average oxygen saturation
      decrease 3 min after procedure in the sucrose groups was significantly lower than
      that in the glucose groups (P < 0.01). The average pain score 3, 5, 10 min after
      procedure was significantly lower than those in the placebo group (P < 0.01). The
      average pain score 3 min after procedure in the sucrose groups was significantly
      lower than that in the glucose groups (P < 0.01). CONCLUSION: Oral administration
      of sweet solutions is an effective way to relieve neonatal pain on procedure, and
      sucrose has a better pain relief action than glucose, moreover, 30% sucrose
      provides better effect in control of heart rate increase 3 min after heel lance,
      but the best concentration of sucrose for pain relief needs further study.

PMID- 24330984
TI  - [A cross-sectional study on the effect of virological response after HAART on
      subsets of T lymphocytes and expression of CD127 in pediatric AIDS patients with
      different viral loads].
AB  - OBJECTIVES: To study the effect of HAART on subsets of T lymphocytes and
      expression of CD127 on memory and naive CD4(+) and CD8(+)T cells in pediatric
      AIDS patients with different viral loads receiving HAART. METHOD: A cross-
      sectional study on 194 pediatric AIDS patients receiving HAART was carried out
      and 52 age matched healthy children were recruited as controls. The percentage of
      CD4(+), CD8(+), CD8(+)CD45RA(+)CD127(+/-), CD8(+)CD45RO(+)CD127(+/-),
      CD4(+)CD45RA(+)CD127(+/-) and CD4(+)CD45RO(+)CD127(+/-)T cells was tested using
      flow cytometry, and HIV-RNA in plasma was detected by quantitative RT-PCR.
      RESULT: The percentage of memory (CD45RO(+)) CD4(+)T cells decreased to (45.73 +/
      8.85)%, and that of naive (CD45RA(+)) CD4(+) and memory CD8(+)T increased to
      (60.44 +/- 5.01)% and (54.69 +/- 7.71) % respectively in the pediatric AIDS
      patients vs. controls (P < 0.05). The percentage of naive (CD45RA(+)) CD4(+)T
      cells of patients with viral load (VL) < 400 copies/ml was (65.57 +/- 5.33) %,
      which was significantly higher than that of patients with VL >= 400 copies/ml (P
      < 0.05).Of patients with VL < 400 copies/ml, the percentage of CD4(+)CD127(+)T
      cells, especially the subset of memory CD4(+)CD127(+)T cells was (82.35 +/-
      2.31)%, which was higher than that of patients with VL >= 400 copies/ml, but
      lower than that of controls (P < 0.05). The percentage of memory and naive
      CD8(+)CD127(+)T cells was lower than that of controls (P < 0.05). CONCLUSION: The
      recovery of CD4(+)T cell subsets in pediatric AIDS patients is associated with
      viral load. Effective HAART can increase the percentage of naive CD4(+)T cells
      and the life of memory CD4(+)T cells.

PMID- 24330985
TI  - [The first confirmed pediatric case with H7N9 avian influenza virus infection in
      China].
AB  - OBJECTIVE: To understand the clinical and epidemiological aspects of avian
      influenza A (H7N9) virus infection in children. METHOD: The clinical data of the
      first confirmed pediatric case of avian influenza A(H7N9) virus infection were
      collected, and the epidemiological information, presenting symptoms, laboratory
      investigation, management and outcome were analyzed. The data of the pediatric
      cases were also compared with those of the adults cases. RESULT: The case
      reported in this paper was a previously healthy 3.6-year-old boy residing in
      rural area of Shanghai. He had onset of fever and mild rhinorrhea on 31 March
      2013 and he was afebrile and well since April 3. Influenza A (H7N9) virus was
      detected in his nasopharyngeal sample collected on 1 April through national
      Influenza-like Illness surveillance using real-time reverse transcriptase PCR and
      virus culture.His family raised domestic poultry with no apparent disease and
      there was no virological evidence of H7N9 infection. Monitoring and testing of 16
      contacts had not found any secondary infection. CONCLUSION: The clinical course
      of H7N9 avian influenza virus infection in children was relatively mild as
      compared to adult cases. The source of infection and detail of exposure for
      children have not been known yet. Continued surveillance studies of mild and
      severe respiratory disease and subclinical infection are essential to further
      characterize the epidemiology and clinical spectrum of this emerging H7N9 virus
      infection in children.

PMID- 24330986
TI  - [A multicenter randomized parallel-controlled study on the efficacy and safety of
      er xie ting granules in children with acute diarrhea].
AB  - OBJECTIVE: To evaluate the efficacy and safety of ER XIE TING GRANULES in
      children with acute diarrhea. METHOD: A multicenter, randomized, open-label,
      parallel-controlled clinical trial was carried out in 15 hospitals during March
      2011 to July 2012. A total of 1489 children with acute diarrhea were enrolled and
      divided randomly into two groups and treated with ER XIE TING GRANULES (treatment
      group) and smectite powder (control group). The therapeutic efficacy and adverse
      drug reactions were evaluated after three-day and seven-day therapy.Superiority
      or non-inferiority test was done for effectiveness of the treatment based on
      efficacy differ by more than 10% regarded as the superiority. RESULT: Totally
      1458 children completed the study, in whom 726 children received ER XIE TING
      GRANULES and 732 received smectite powder. After three-day and seven-day therapy,
      cure rates and total efficacy rates of the treatment group were 44.2%, 94.1%,
      88.8%, and 97.9% separately and higher than those of control group (39.3%, 88.4%,
      83.9%, 97.4%) ( Z = 3.2, P < 0.01; Z = 2.46, P < 0.05). There were 520 children
      with rotavirus infection and in whom 266 cases received ER XIE TING GRANULES and
      254 received smectite powder. For rotavirus enteritis, cure rates and total
      efficacy rates of the treatment group after three-day and seven-day therapy were
      40.6%, 95.1%, 89.9%, and 98.9% separately and higher than those of control group
      (26.4%, 84.3%, 78.8%, and 96.8%) (Z = 4.807, P < 0.01;Z = 3.519, P < 0.01). The
      lower limits of the 95% confidence interval of difference of cure rate and total
      efficacy rates after three-day and seven-day therapy between two groups were less
      than 10%.No obvious drug related adverse reactions were found during the study.
      CONCLUSION: ER XIE TING GRANULES has the same effect for treatment of acute
      diarrhea and rotavirus enteritis in children.No obvious drug related adverse
      reactions were found.

PMID- 24330987
TI  - [Diagnosis and treatment of epilepsy and narcolepsy comorbid].
AB  - OBJECTIVE: To analyze the clinical diagnosis and treatment process of narcolepsy
      and epilepsy co-existence, and thereby to improve awareness of such cases.
      METHOD: The clinical manifestations of 2 cases were observed, and video
      electroencephalogram (VEEG), multiple sleep latency tests (MSLT) were performed.
      Hypocretin 1 level in cerebrospinal fluid was examined in one case. RESULT: The
      onset of disease of case one was started with epilepsy with myoclonic seizure.
      After half a year, catalepsy induced by emotion especially laughing and excessive
      daytime sleepiness appeared. MSLT was positive and hypocretin 1 level decreased.
      Narcolepsy-cataplexy was definitely diagnosed in this case. Valproate was given
      and seizure was controlled completely, but the excessive daytime sleepiness was
      aggravated. Combination of valproate, methylphenidate and clomipramine treatment
      improved the symptoms of narcolepsy and the patient was still free of epileptic
      seizures. The onset symptoms of case 2 were catalepsy and excessive daytime
      sleepiness. MSLT was positive. The treatment was ineffective because of bad
      compliance. After 2 years, episodes of impairment of consciousness with
      automatism occurred. VEEG showed slow waves and spikes in right temporal area.
      Complex partial seizure was determined. Oxcarbazepine was used and then the
      patients became seizures free, but the symptoms of narcolepsy were still obvious.
      CONCLUSION: Comorbidity of narcolepsy and epilepsy is a rare phenomenon. Clinical
      symptoms, predisposing factor, VEEG and MSLT can help diagnosis and differential
      diagnosis. The antiepileptic drugs might aggravate drowsiness. Based on therapy
      of epilepsy by using antiepileptic drugs, low dosage of central nervous system
      stimulants might improve the drowsiness and catalepsy symptoms of narcolepsy.

PMID- 24330988
TI  - [Two cases of Shwachman-Diamond syndrome with genetic confirmation and literature
      review].
AB  - OBJECTIVE: To study clinical features and gene mutations in Shwachman-Diamond
      syndrome (SDS), a rare autosomal recessive disease, in children. METHOD: Clinical
      manifestations, laboratory examinations, image studies, and genetic testing of
      two cases with SDS were presented, analyzed, and discussed; 311 SDS cases from
      the related literature since 2004 were reviewed. RESULT: (1) The two cases both
      presented with characteristic exocrine pancreatic insufficiency evidenced by
      abnormal pancreas on imaging and growth retardation, persistent or intermittent
      neutropenia (<1500*10(6)/L) and/or anemia, and skeletal abnormalities. Analysis
      of the SBDS gene revealed the same compound heterozygous genotype (c.183_184TA >
      CT, c.258+2T > C) for both subjects. This genotype is the result of the
      inheritance of abnormal alleles from both healthy parents. (2) Among 311 cases,
      75 cases having complete clinical data were characterized by exocrine pancreatic
      dysfunction (61/75; 81.3%), hematologic abnormalities with single- or multi
      lineage cytopenia (64/75; 85.3%), and bone abnormalities (47/75; 62.7%).
      c.183_184TA > CT, c.258+2T > C, and c. [ 183_184TA > CT; 258+2T > C] are the
      major types of SBDS gene mutation(85/138;61.6%). CONCLUSION: SDS is characterized
      by exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth
      failure; hematologic abnormalities with single- or multi-lineage cytopenia, and
      bone abnormalities. The diagnosis of SDS relies on a combination of clinical
      features and gene-based tests. The SDS patients need long term follow-up and
      management.

PMID- 24330989
TI  - [Gene analysis and literature review of autosomal recessive polycystic kidney
      disease].
AB  - OBJECTIVE: The purpose of this study was to investigate the clinical and genetic
      characteristics of autosomal recessive polycystic kidney disease. METHOD:
      Targeted sequencing was used on a children who was accurately diagnosed as
      autosomal recessive polycystic kidney disease in Peking Union Medical College
      Hospital to analyze the major clinical manifestations of the disease. An analysis
      of the PKHD1 genes was made on the patient, and then verified by polymerase chain
      reaction (PCR). And the related literature was reviewed also. RESULT: The patient
      was a boy, 2 years and 3 months old, and had abdominal distention for about one
      year. The abdominal ultrasound suggested diffuse liver lesions, mild intrahepatic
      bile duct dilatation, structure disturbance of both kidneys, appearance of
      multiple strong echo. The child was clinically highly suspected of polycystic
      kidney disease. Targeted sequencing showed two mutations in exon 32 and exon 50
      of PKHD1 gene, respectively, c.4274T > G, leading to p.Leu1425Arg, c.7973T > A,
      leading to p.Leu2658Ter. Verified by PCR, the father has one mutation of c.4274T
      > G. CONCLUSION: The clinical manifestations of autosomal recessive polycystic
      kidney disease are multiple renal cyst, cyst of liver and liver fibrosis,
      intrahepatic bile duct dilatation. Two mutations (c.4274T > G, c.7973T > A) in
      PKHD1 gene may be pathogenic.

PMID- 24330990
TI  - [Neonatal group B streptococcus infection in the Children's Hospital of Gansu
      Province through PCR array].
AB  - OBJECTIVE: To study neonatal Streptococcus agalactiae (GBS) infection in The
      Children's Hospital of Gansu Province through Polymerase Chain Reaction(PCR)
      Array. METHOD: After obtaining the informed consent from parents or guardians,
      blood samples of 286 neonates were collected and studied in The Children's
      Hospital of Gansu Province from June 2011 to January 2012. DNA of the selected
      samples was extracted through the method of 5% Chelex-100 + 0.5% NP40 solution.
      Twenty-five genes were ultimately selected and then 25 pairs of primers were
      designed respectively through primer-BLAST tool of NCBI database.For every
      primer, PCR conditions were optimized through the identified GBS, and 25 pairs of
      primers were arrayed as to be used to study neonatal GBS infection. RESULT: The
      results of PCR Array showed that the 14 samples were detected positive,
      accounting for 4.90% of all the selected specimens. As for neonatal GBS
      infection, the positive rate was 4.55% within 7 days after birth and 5.19% in
      those older than 7 days. The positive rate of 53 preterm infants was 5.66%. The
      follow-up survey showed that none of the cases died. CONCLUSION: In the
      Children's Hospital of Gansu Province neonatal GBS infection rate was 4.90%,
      which is similar to the previous domestic reports, but is lower than the reports
      from Europe and the United States.Studies have shown that the gene expression
      related to immune evasion has a higher frequency. The present study suggests that
      the strategy of GBS immune adaptation may play an important role in neonatal GBS
      infection.

PMID- 24330991
TI  - [A case of hyperimmunoglobulin E syndrome with pneumoangiogram lesion in Mainland
      Chinese child].

PMID- 24330992
TI  - [Report of a case with small intestinal telangiectasis].

PMID- 24330993
TI  - [X-linked hypohidrotic ectodermal dysplasia:a case report].

PMID- 24330994
TI  - [A case of 9p partial monosomy syndrome].

PMID- 24330995
TI  - [Experts' consensus on long-term management of children with epilepsy].

PMID- 24330996
TI  - [Development and application of 2006 WHO Child Growth Standards].

PMID- 24330997
TI  - [Status quo and progress of research on screening methods of nutritional risk of
      pediatric patients].

PMID- 24330998
TI  - [Ring chromosome 20 syndrome].

PMID- 24330999
TI  - [Meeting minutes of the 1(st) developmental and behavioral pediatric summit forum
      in China].

PMID- 24331000
TI  - [Interpretation of WHO Global Strategy for Infant and Young Children Feeding].

PMID- 24331003
TI  - Mariapaola Martinelli's ultra flat space.

PMID- 24331002
TI  - Tea consumption and risk of type 2 diabetes: a dose-response meta-analysis of
      cohort studies.
AB  - Tea consumption has inconsistently been shown to be associated with the risk of
      type 2 diabetes (T2D). The aim of the present study was to conduct a dose
      response meta-analysis of cohort studies assessing the association between
      consumption of tea and risk of developing T2D. Pertinent studies were identified
      by searching PubMed, Web of Science and EMBASE through 31 March 2013. A total of
      sixteen cohorts from fifteen articles that reported 37,445 cases of diabetes
      among 545,517 participants were included. A significant linearly inverse
      association between tea consumption and T2D risk was found (P for linear trend =
      0.02). An increase of 2 cups/d in tea consumption was found to be associated with
      a 4.6 (95% CI 0.9, 8.1) % reduced risk of T2D. On the basis of the dose-response
      meta-analysis, the predicted relative risks of diabetes for 0, 1, 2, 3, 4, 5 and
      6 cups of tea consumed per d were 1.00 (referent), 0.97 (95% CI 0.94, 1.01),
      0.95(95% CI 0.92, 0.98), 0.93 (95% CI 0.88, 0.98), 0.90 (95% CI 0.85, 0.96), 0.88
      (95 % CI 0.83, 0.93) and 0.85 (95% CI 0.80, 0.91), respectively. There was a
      statistically significant heterogeneity within the selected studies (Q= 45.32, P<
      0.001, I 2= 60.3 %). No evidence of substantial small-study bias was found (P=
      0.46). Our findings suggest that tea consumption could be linearly inversely
      associated with T2D risk. Future well-designed observational studies that account
      for different characteristics of tea such as tea types, preparation methods and
      tea strength are needed to fully characterise such an association.

PMID- 24331004
TI  - Application of the NucliSENS easyMAG system for nucleic acid extraction:
      optimization of DNA extraction for molecular diagnosis of parasitic and fungal
      diseases.
AB  - During the last 20 years, molecular biology techniques have propelled the
      diagnosis of parasitic diseases into a new era, as regards assay speed,
      sensitivity, and parasite characterization. However, DNA extraction remains a
      critical step and should be adapted for diagnostic and epidemiological studies.
      The aim of this report was to document the constraints associated with DNA
      extraction for the diagnosis of parasitic diseases and illustrate the adaptation
      of an automated extraction system, NucliSENS easyMAG, to these constraints, with
      a critical analysis of system performance. Proteinase K digestion of samples is
      unnecessary with the exception of solid tissue preparation. Mechanically grinding
      samples prior to cell lysis enhances the DNA extraction rate of fungal cells. The
      effect of host-derived nucleic acids on the extraction efficiency of parasite DNA
      varies with sample host cell density. The optimal cell number for precise
      parasite quantification ranges from 10 to 100,000 cells. Using the NucliSENS
      easyMAG technique, the co-extraction of inhibitors is reduced, with an exception
      for whole blood, which requires supplementary extraction steps to eliminate
      inhibitors.

PMID- 24331005
TI  - Recent trends of body mass index distribution among school children in Sendai,
      Japan: Decrease of the prevalence of overweight and obesity, 2003-2009.
AB  - SUMMARY: It was reported that the number of obese children increased during the
      final decades of the 20th century. However, it is unclear whether the prevalence
      of obesity has changed in recent years. The aim of this study was to examine
      trends in the body mass index (BMI) and prevalence of obesity in 6th grade
      primary school children (6thPS) and 3rd year junior high school students (3rdJHS)
      in Sendai, Japan between 2003 and 2009. BMI (kg/m(2)) was calculated and the
      prevalences of overweight and obesity were defined based on internationally
      agreed cutoff points. The mean BMI significantly decreased during the study
      period in all groups. In addition, the results of regression analysis revealed
      that significant decreases in BMI occurred in all percentiles in all groups as
      well. The mean prevalence rates of overweight and obese children as defined by
      international reference values during the observation period were 19.5% and 4.1%
      for boys in 6thPS, 13.6% and 2.2% for girls in 6thPS, 13.6% and 3.0% for boys in
      3rdJHS and 12.2% and 1.9% for girls in 3rdJHS, respectively. There was a
      significant decreasing trend in the proportion of overweight and obese children
      from 2003 to 2009. The downward shifts of BMI might be due to effect modification
      in the lifestyle of children. Since we had no further data for characterization
      of Sendai school children and the period of this observation was only 7 years,
      the reasons for the change in the prevalence of obesity in this population remain
      speculative.:

PMID- 24331006
TI  - Effect of exercise performed at anaerobic threshold on serum growth hormone and
      body fat distribution in obese patients with type 2 diabetes.
AB  - SUMMARY: The mechanism by which exercise reduces visceral fat is not fully
      understood. We have reported that increase in serum growth hormone (GH) level by
      mild exercise is associated with increase in lipolysis in type 2 diabetes (T2D),
      and that GH stimulates lipolysis in rat visceral adipose tissue. The aim of this
      study was to investigate the effect of GH secretion in response to exercise on
      visceral fat in obese subjects with T2D. Subjects were divided into exercise (n =
      11) and non-exercise (n = 8) groups. Exercise was performed at anaerobic
      threshold (AT). Blood samples were obtained at weeks 0 and 4. To evaluate the
      secretion of GH and catecholamines in response to exercise, serum GH and
      catecholamines levels were measured before and after a bout of exercise on day 1.
      Visceral fat area (VFA) reduction tended to be greater in exercise group compared
      to non-exercise group (p = 0.067), whereas subcutaneous fat area (SFA) reduction
      was not different between two groups. In exercise group, serum GH level tended to
      increase during exercise, while catecholamines showed no significant changes. The
      change in serum GH level correlated negatively with the change in VFA during this
      study, but did not correlate with SFA. The increase in serum insulin-like growth
      factor-I level in exercise group was 10-fold higher than that in non-exercise
      group. These results suggest that in obese patients with T2D, exercise performed
      at AT may reduce visceral fat and the reduction appears to be associated with GH
      secretion but not with catecholamine in response to exercise.:

PMID- 24331007
TI  - A clinical follow-up study on the risk of cerebral infarction in Chinese aging
      overweight and obese population.
AB  - SUMMARY: The current studies have shown that overweight and obesity are possible
      risk factors for cerebral infarction, but variety of weight status in the role of
      the mechanism of cerebral infarction is not yet fully understood. In our
      research, a prospective cohort follow-up study of 8 years (2002-2009) was used to
      analyze the correlation of weight, cerebral infarction and other factors in 1170
      Han retired employees from KaiLuan Group. The study included enrolling with
      questionnaire survey, medical examination, brain CT scan and so on, based on the
      changes in body mass index from the beginning to the end of the follow-up study,
      the subjects were divided into eight groups: stay normal weight group (n = 364),
      stay overweight group (n = 171), development from overweight into obesity group
      (n = 95), stay obesity group (n = 37), development from normal weight into
      overweight group (n = 365), development from normal weight into obesity group (n
      = 63), overweight improved group (n = 55) and obesity improved group (n = 20). We
      found that the incidence of cerebral infarction in the stay overweight group was
      higher than in the stay obese and stay normal weight groups (25.15%, 18.92%,
      19.23%, P < 0.05) during the last medical examination in the end of follow-up
      study, and relative risk was 1.31, 0.98, 1, and population attributable risk was
      0.10, -0.002, 0, respectively. But there was no difference of the incidence of
      cerebral infarction between stay obesity group and stay normal weight group (P >
      0.05). The incidence of hypertension in the development of normal weight into
      obesity group and stay obesity group was higher than stay overweight group and
      stay normal weight group (63.49%, 56.76%, 48.54%, 36.54%, P < 0.05), while the
      aggregated incidence of risk factors in above mentioned four groups was 75%, 64%,
      63%, 55% (P < 0.05), respectively. In logistic regression analysis of correlative
      factors to cerebral infarction, waist circumference in the last checkup,
      diabetes, development from normal weight to overweight status, etc were selected
      (P < 0.01), and odds ratio (OR) values were 0.98, 6.51, 4.13 (P < 0.05),
      respectively. The incidence of cerebral infarction in overweight improved and
      obesity improved groups were 29.09%, 45.00%, relative risk values were 1.51,
      2.34, the aggregated incidence of risk factors were 48%, 65%. This study showed
      that Chinese aging population who has overweight with a significant overweight
      stable phase and with no overweight stable phase but progressing to obesity had
      different risks of diseases. The former was at high risk of cerebral infarction,
      the latter was susceptible to hypertension. In the aging population of overweight
      and obesity, the aggregated incidence of cerebral infarction related risk factors
      were significantly increased, and weight-loss treatment did not reduce the
      incidence of cerebral infarction. Thus, the aging patients with obesity should be
      actively treated to eliminate hypertension and other risk factors, rather than an
      appetite for weight-loss treatment.:

PMID- 24331008
TI  - Obesity prevalence, waist-to-height ratio and associated factors in adult Turkish
      males.
AB  - SUMMARY: This study was performed to determine the obesity prevalence and
      associated risk factors in aged 20 and over years old males living in 11 towns in
      Kayseri, Turkey between July and August 2007. 1530 men were recruited, of which 6
      were excluded because of incomplete information. Data were collected by a
      questionnaire. Body weight, height, waist and hip circumferences were measured.
      Body mass index (BMI) of 25.0-29.9 kg/m(2) was accepted as overweight and above
      30 kg/m(2) as obesity, waist-to-hip ratio (WHpR) > 1.0 and waist-to-height ratio
      (WHtR) >= 0.5 were accepted as abdominal obesity. Chi-square and logistic
      regression tests were performed. According to BMI, overweight and obesity
      prevalences were 39.6% and 16.9%, respectively. Obesity prevalence was 29.9% (50
      59 years) according to WHpR, 50.4% (60-69 years) according to waist circumference
      (WC) and 24.8% (40-49 years) according to WHtR. The logistic regression analysis
      revealed age of 60-69 years, being a graduate from university, being widowed and
      having positive familial history of obesity as risk factors of having BMI >= 25
      kg/m(2). In conclusion, obesity is a serious issue for the males residing in
      Kayseri and among the anthropometric measurements WHtR is a simple and effective
      index to identify health related risks even in male of younger ages.:

PMID- 24331009
TI  - Relationship of body mass index and waist-to-hip ratio with fibrinolytic activity
      measured as D-dimer.
AB  - SUMMARY:  BACKGROUND/AIMS: Increased coagulability or impaired fibrinolysis may
      partly explain how obesity increases cardiovascular disease risk. However, there
      has been some controversy regarding the relationship of anthropometric measures,
      like body mass index (BMI) and waist-to-hip ratio (WHR), and D-dimers. We aimed
      to determine the relationship of general and visceral obesity to D-dimer in a
      group of outpatients with different BMI and WHR ranges. METHODS: We performed a
      cross-sectional study with adult patients from an outpatient primary health
      service. BMI, WHR and triceps skin fold were measured. Blood samples were
      collected from all patients and D-dimer levels were obtained. RESULTS: A total of
      66 patients were included in the analysis. The patients had a mean age of 54.6 +/
      15.3 years. Fifty-three (80.3%) patients were female and 13 (19.7%) were male.
      The mean BMI, WHR and triceps skin fold were 30.1 +/- 6.9 kg/m(2), 0.88 +/- 0.08,
      20.9 +/- 7.6 mm, respectively. For all the study group, D-dimers were positively
      correlated only with WHR (r = 0.27, p = 0.038). D-Dimers values were not related
      to BMI and to triceps skin fold. D-Dimers were moderately correlated with WHR in
      women (r = 0.40, p = 0.021), but not in male patients (r = 0.18, p = 0.601).
      CONCLUSIONS: Our results suggest that abdominal obesity may lead to disturbances
      in hemostasis, at least in female patients.

PMID- 24331010
TI  - The use of adipose tissue-conditioned media to demonstrate the differential
      effects of fat depots on insulin-stimulated glucose uptake in a skeletal muscle
      cell line.
AB  - SUMMARY: We aimed to study the depot-specific effect of adipose tissue on insulin
      sensitivity of skeletal muscle in vitro. Adipose tissue-conditioned medium (CM)
      was generated from visceral and subcutaneous fat from obese subjects. CM from
      visceral as compared to subcutaneous fat had higher concentrations of interleukin
      (IL)-6 (15-fold; P < 0.05) and IL-8 (8-fold; P < 0.05). CM from visceral fat
      (1:128 dilution) reduced insulin-stimulated glucose uptake in L6 myotubes by 19%
      (P < 0.05), an effect mediated by a nuclear factor kappa B (NFkappaB)/mammalian
      target of rapamycin complex 1 (mTORC1)-dependent pathway and partially reversed
      by neutralizing IL-6. IL-6 at a concentration comparable to that in CM from
      visceral fat reduced insulin-stimulated glucose uptake by 53% (P < 0.05), an
      effect abolished by inhibiting NFkappaB or mTORC1. We demonstrated the utility of
      the CM-myotube system and identified IL-6 as a major cytokine mediating visceral
      fat-induced muscle insulin resistance.:

PMID- 24331011
TI  - Changes in 'extra' food intake among Australian children between 1995 and 2007.
AB  - SUMMARY:  OBJECTIVE: To examine the consumption patterns of energy-dense,
      nutrient-poor 'extra' foods among Australian children and to determine any
      changes in consumption since the 1995 National Nutrition Survey (1995 NNS).
      METHODS: 'Extra' food consumption was analysed by age group and gender using 24-h
      recall data from the 2007 Australian National Children's Nutrition and Physical
      Activity Survey (2007 Survey; n = 4380) and the 1995 NNS (n = 2435). Differences
      in percent consuming, amounts consumed and percent energy contribution were
      assessed. RESULTS: 'Extra' foods contributed 35% to daily energy intake in the
      2007 survey, ranging from 24% in the 2-3 year olds to 38% in the 9-13 and 14-16
      year olds. The foods contributing most to energy intake included 'fried potatoes'
      (2.9%), 'cakes, muffins, slices' (2.9%) and 'potato crisps and similar snacks'
      (2.6%). Compared to the 1995 NNS, total energy intake was significantly lower in
      the 2007 Survey (8621 kJ in 1995 versus 8330 kJ in 2007), as was the consumption
      of 'extra' foods (both in terms of weight and energy) (3645 kJ in 1995 versus
      3049 kJ in 2007). All age groups reported a decline in energy intake from 'extra'
      foods of approximately 600 kJ. CONCLUSION: The overall consumption of 'extra'
      foods seems to have decreased from 1995 to 2007. However, 'extra' foods continue
      to be over-consumed by Australian children and continuous monitoring of 'extra'
      foods consumption is highly warranted.

PMID- 24331012
TI  - Total reversal of weight loss from adjustable gastric banding surgery associated
      with excessive intake of energy dense liquid and solid foods: A case report.
AB  - SUMMARY: We report excessive binging and total reversal of weight loss in a
      patient after adjustable gastric banding surgery (AGBS). A 42-year-old female who
      underwent AGBS 4 years earlier was randomized to a diet group in a study on
      exercise training. The patient was on therapy for pre-diabetes and depression.
      She weighed 115 kg pre-surgery, lost 27.3 kg post-surgery, and weighed 117.3 kg
      at the start of the study. Her energy intake, assessed by 3-day food record, was
      14,096 kcal/d at the beginning of the study of which 3086 kcal/d was from liquid
      and 7273 kcal/d from solid energy dense foods. The patient reported that the
      liquid foods facilitated binging on solid foods despite gastric band adjustments.
      Following intensive dietary counseling for 5 weeks, her reported energy intake
      decreased to <3000 kcal/d and body weight by 1 kg. Evaluating and actively
      addressing any dietary behavioral issues before and after AGBS are recommended.:

PMID- 24331013
TI  - Bariatric surgery to treat severely obese patients with type 2 diabetes: A
      consensus statement.

PMID- 24331014
TI  - Significant progress made in hepatitis B control in China.

PMID- 24331015
TI  - The inception, achievements, and implications of the China GAVI Alliance Project
      on Hepatitis B Immunization.
AB  - The China GAVI Hepatitis B Immunization Project was initiated in 2002 with the
      signing of a Memorandum of Understanding between GAVI and the Government of
      China. The Project was one of the three (China, India, and Indonesia) GAVI
      initiated special projects done to support countries too large to receive full
      GAVI support for hepatitis B vaccine and safe injections. The Project in China
      was designed by the Chinese Government and partners to deliver free hepatitis B
      vaccine and safe injections to all newborns in the 12 Western Provinces and
      Poverty Counties in 10 Provinces of Central China (1301 Counties with
      approximately 5.6 million births per year), eliminating the gap in immunization
      coverage between wealthier and poorer regions of China. The project budget (USD
      76 million) was equally shared by GAVI and the Chinese Government. Initially
      planned for 5 years, two no cost extensions extended the project to 2011.
      Although China produced hepatitis B vaccine, before the project the vaccine was
      sold to parents who were also charged a "user fee" for the syringe and vaccine
      administration. Basic Expanded Program on Immunization (EPI) vaccines such as
      BCG, DTP, Polio, and measles vaccines were provided free to parents, although
      they were charged a user fee. Vaccines were sold by China CDC Offices at
      provincial, prefecture, county level and township hospitals, and village doctors
      received a substantial portion of their income from the sale of hepatitis B and
      other vaccines. The result of charging for hepatitis B vaccine was that coverage
      was relatively high in Eastern and wealthier counties in Central China (~80-90%),
      but was much lower (~40%) in Western China and Poverty Counties where parents
      could not afford the vaccine. The Project was administered by the China MOH and
      China CDC EPI program, and two Project Co-managers, one from the Chinese
      Government and the other an international assignee, were chosen. The project had
      an oversight Operational Advisory Group composed of the Chinese Government, WHO,
      UNICEF, and GAVI. The initial targets of the project as delineated in the initial
      MOU for the Project areas (HepB3 coverage will reach 85% at the county level,
      >75% of newborns at the county level will receive the first dose of hepatitis B
      within 24h of birth, and all immunization injections will be with auto disable
      [AD] syringes) were substantially exceeded. The differential in vaccine coverage
      between wealthier and poorer parts of China was eliminated contributing to a
      great improvement in equity. With additional contributions of the Chinese
      Government the Project was accomplished substantially under budget allowing for
      additional catch up immunization of children under 15 years of age. More than 5
      million health workers were trained in how to deliver hepatitis B vaccine, timely
      birth dose (TBD), and safe injections, and public awareness of hepatitis B and
      its prevention rose significantly. TBD coverage was expedited by concurrent
      efforts to have women deliver in township clinics and district hospitals instead
      of at home. The effective management of the Project, with a Project office
      sitting within the China EPI and an Operational Advisory Group for oversight,
      could serve as a model for other GAVI projects worldwide. Most importantly, the
      carrier rate in Chinese children less than 5 years of age has fallen to 1%, from
      a level of 10% before the inception of the Project. Liver cancer, one of the
      major cancer killers in China (250,000-300,000 annual estimated deaths), will
      dramatically decline as immunized cohorts of Chinese children age. While
      hepatitis C and non-alcoholic liver disease also exist in China and can lead to
      liver cancer and cirrhosis, the majority of liver disease in China is hepatitis B
      related and therefore preventable. The authors believe that China's success in
      preventing hepatitis B is one of the greatest public health achievements of the
      21st century. Work remains to be done in several key areas. There are still
      pockets of home births in rural provinces where a TBD is difficult to deliver,
      and China is strengthening its policy of screening pregnant women for HBsAg and
      delivering HBIG plus vaccine to newborns of HBV carrier mothers. Approximately
      10% of the adult population of China remain chronic carriers of hepatitis B virus
      and cannot be helped by the vaccine, so prevention of liver cancer and cirrhosis
      in those groups remains a future challenge for China.

PMID- 24331016
TI  - Foreword. Hepatitis B and the impact of immunization in China and the WHO Western
      Pacific Region.

PMID- 24331017
TI  - Preventing hepatitis B though universal vaccination: reduction of inequalities
      through the GAVI China project.
AB  - OBJECTIVE: In order to measure hepatitis B coverage and progress in equality with
      respect to protection against hepatitis B in poverty-affected areas funded by the
      Global Alliance on Vaccine and Immunization project funded in poverty-affected
      counties. METHODS: We reviewed routinely reported coverage data and conducted a
      national stratified, validation, cross-sectional survey in October 2010,
      according to WHO recommended sampling method. First, we stratified China into
      three regions (Eastern, Central and Western) based on economic criteria. Second,
      in each region, we selected eight counties with a probability proportional to
      population size. Third, in each selected county, we selected (a) 10 townships at
      random among the list of townships of the county. RESULTS: We visited 244
      townships as part of the final evaluation (71 in the East, 86 in the Center and
      87 in the West). Overall, in these 244 townships, surveyed TBD coverage increased
      from 60% in 2002 to 91% in 2009 and surveyed three dose of hepatitis B vaccine
      coverage increased from 71% in 2002 to 93% in 2009. Overall, in the GAVI
      supported areas, the HepB3/DTP3 ratio increased from 57% in 2002 to 94% in 2009.
      CONCLUSION: Pro-poor GAVI approach was an effective way to reduce inequity among
      children through provision of free vaccination. When vaccine and AD syringes were
      provided for free, they closed the gap between Eastern and Western regions and
      between the rich and the poor.

PMID- 24331018
TI  - The China GAVI Project.

PMID- 24331019
TI  - Evaluation of policies and practices to prevent mother to child transmission of
      hepatitis B virus in China: results from China GAVI project final evaluation.
AB  - BACKGROUND: Mother to Child Transmission (MTCT) has remained a leading cause of
      HBV infection in China, accounting for 40% of total infections. Providing
      hepatitis B vaccine (HepB) to all infants within 24h of birth (Timely Birth Dose,
      TBD), and subsequent completion of at least 3 vaccine doses is key to preventing
      perinatal HBV infection. In 2002, with the financial support of the Global
      Alliance on Vaccine and Immunization (GAVI) targeted to Western region and 223
      poverty-affected counties in Central region, hepatitis B vaccine was provided for
      free. In 2010, we evaluated the China GAVI project in terms of its activities to
      prevent perinatal infections. OBJECTIVE: The objectives of the evaluation were to
      (1) measure achievements in the China GAVI project in terms of TBD coverage, and
      (2) describe practices for HBsAg screening of pregnant women and HBIG use outside
      the GAVI China project. METHODS: We used the methods recommended by WHO to select
      a cluster sample of health care facilities for the purpose of an injection safety
      assessment. We stratified China into three regions based on economic criteria,
      and selected eight counties with a probability proportional to population size in
      each region. In each selected county, we selected (a) 10 townships at random
      among the list of townships of the county and (b) the one county level hospital.
      In each hospital, we abstracted 2002 through 2009 records to collect information
      regarding birth cohorts, hospitals deliveries, vaccine management, hepatitis B
      vaccination delivery, HBsAg screening practices and results, and HBIG
      administration. In addition, in all hospitals, we abstracted records regarding
      the delivery of TBD. RESULTS: We visited 244 facilities in the three regions,
      including 24 county hospitals and 220 township hospitals. We reviewed 837,409
      birth summary records, 699,249 for infants born at county or township hospitals.
      Hospital delivery rates increased from 58% in 2002 to 93% in 2009. Surveyed TBD
      coverage increased from 60% in 2002 to 91% in 2009 (+31%). Surveyed TBD coverage
      among children born in hospitals increased from 73% in 2002 to 98% in 2009.
      Between 2002 and 2009, the proportion of pregnant women screened for HBsAg
      increased from 64% in 2002 to 85% in 2009. In 2009, the proportion of infants
      born to women screened and found to be HBsAg positive who did not receive any
      immunization within 24h after birth ranged from 0% to 0.7% across regions.
      CONCLUSIONS: Increased availability of hepatitis B vaccine, along with efforts to
      improve hospital deliveries, increased TBD coverage in China. This decreased
      perinatal HBV transmission and will reduce disease burden in the future.
      Screening for HBsAg to guide HBIG administration has begun, but with
      heterogeneous immuno-prophylaxis practices and a poor system for follow up.

PMID- 24331020
TI  - Evaluation of immunization injection safety in China, 2010: achievements, future
      sustainability.
AB  - OBJECTIVE: The study objectives were to evaluate injection practices in China in
      the post GAVI project era and provide guidance for policy makers to update
      national standards for injection practices and further improve vaccination
      services. METHODS: We conducted a national stratified, cross-sectional survey in
      October 2010, according to WHO recommended sampling methods. First, we stratified
      China into three regions (Eastern, Central and Western) based on economic
      criteria. Second, in each region, we selected eight counties with a probability
      proportional to population size. Third, in each selected county, we selected (a)
      10 townships at random among the list of townships of the county and (b) the one
      county level hospital. RESULTS: With respect to the risk to the patient, we never
      observed open injection equipment lying around or needles left in the septum of
      multi-dose vials. We never observed sterilizable injection devices syringes in
      any of the facilities. The proportion of facilities using sharps containers was
      highest in the East (85%), intermediate in the West (79%) and lowest in the
      Central region (56%). In 2009, auto-disable syringes and safety boxes were used
      in 78% and 79% facilities in GAVI supported areas of the Western region,
      respectively. Only one facility presented evidence of attempts to re-sterilize
      disposable injection equipment in the Eastern region. CONCLUSIONS: Use of AD
      syringe and sharps containers increased in vaccination services in China,
      especially in GAVI supported areas, leading to sustainable progress in terms of
      elimination of reuse of injection devices. However, risk to patients still
      existed, including persisting use of standard disposable syringes and attempts to
      re-use disposable devices.

PMID- 24331021
TI  - Improving hepatitis B vaccine timely birth dose coverage: lessons from five
      demonstration projects in China, 2005-2009.
AB  - BACKGROUND: Delivery of a timely (within 24h) hepatitis B vaccine birth dose
      (TBD) is essential to prevent the long-term complications of hepatitis B virus
      (HBV) infection. China made substantial progress in hepatitis B immunization
      coverage, however, in 2004, TBD coverage was lower in Western, poorer provinces.
      METHODS: We reviewed five demonstration projects for the promotion of TBD in
      rural counties in Qinghai, Gansu and Ningxia. Interventions consisted of (1) work
      to increase TBD coverage in hospitals, including training of health-care workers,
      (2) information, education and communication [IEC] with the population and (3)
      micro-plans to deliver TBD for home births. We evaluated outcome through
      measuring TBD coverage for home and hospital births. RESULTS: These projects were
      implemented in the context of national efforts to promote institutional
      deliveries that lead to increases ranging from 10% to 17% to reach 43-97%
      proportion of institutional births at the end of the projects. Among
      institutional births, TBD coverage increased by 2% to 13% to reach post
      implementation coverage ranging from 98% to 100%. Among home births, TBD coverage
      increased by 7% to 56% to reach post implementation coverage ranging from 29% to
      88%. Overall, TBD coverage increased by 4% to 36% to reach post implementation
      coverage ranging from 82% to 88%. CONCLUSIONS: Demonstration projects based on
      combined interventions increased TBD coverage. Increases in institutional births
      amplified the results obtained. Use of standardized indicators for such projects
      would facilitate evaluation and identify intervention components that are most
      effective.

PMID- 24331022
TI  - Screening of pregnant women for hepatitis B virus surface antigen (HBsAg) and
      subsequent management, Qiandongnan prefecture, Guizhou, China, 2010.
AB  - BACKGROUND: In China, in 2010, a high proportion of pregnant women were tested
      for hepatitis B surface antigen (HBsAg). However, the preventive actions taken
      following screening were unclear. We followed up infants who were born to HBsAg
      positive mothers to describe the management that took place after screening.
      METHODS: We selected eight counties with a probability proportional to population
      size in the Qiandongnan prefecture, Guizhou province. In each county, we selected
      a hospital at random. In each hospital, we (a) reviewed records to estimate the
      proportion of pregnant women who had been screened for HBsAg in 2010 and (b)
      sampled 10 screened women at random to assess management after one year in 2011.
      We calculated proportions and confidence intervals (CI) using standard formulae.
      RESULTS: Among the 7232 women who delivered in 2010 in the 8 hospitals, 98% (95%
      CI: 97%-99%) had been tested for HBsAg. Among 82 HBsAg women sampled for follow
      up, 45 (55%; 95% CI: 44%-65%) knew they had been tested during pregnancy and 60
      (73%; 95% CI: 63%-82%) knew they were HBsAg positive. The 82 infants had received
      three doses of hepatitis B vaccines and 79 (96%; 95% CI: 90%-99%) had received
      the first dose within 24h. However, only 11 infants (13%; 95% CI: 9%-25%) had
      received HBIG in addition to hepatitis B vaccine and 16 (20%; 95% CI: 12%-29%)
      had been tested for HBsAg upon completion of the vaccine series as part of their
      routine management. CONCLUSIONS: HBsAg testing of pregnant women was common in
      Qiandongnan, Guizhou, but post-screening management was limited. There is a need
      to ensure continuity of care through engaging women in HBsAg testing and
      following up infants with comprehensive management, including immunoprophylaxis
      and serological testing.

PMID- 24331023
TI  - The impact of hepatitis B vaccine in China and in the China GAVI Project.
AB  - The China GAVI Project (CGP) was initiated in 2002 to provide hepatitis B (HB)
      vaccine to infants born in the less developed areas of China including the
      Western provinces and poverty counties of Middle provinces, to prevent the
      consequences of hepatitis B virus infection. By 2009, the project areas had
      raised coverage of 3 doses of HB vaccine and timely birth doses to almost 90%
      among infants, comparable to those in wealthier Eastern provinces, and reduced
      HBV prevalence to <1% among children in these areas. We estimated the impact in
      disease prevented by HB vaccine in China between 1992, when the vaccine was
      routinely recommended, and 2009, and in CGP areas for the years 2003-2009, when
      the CGP was active. A published model was used to estimate the burden of chronic
      and acute HBV infection and death prevented due to HB vaccination in China and
      the CGP areas using data from national serosurveys in China in 1992 and 2006, and
      HB vaccine coverage from surveys in 2004, 2006 and 2010. We used sigmoid modeling
      to estimate vaccine coverage nationally, regionally, and CGP areas. We also
      estimated the incremental impact of the CGP on HB vaccine coverage in those
      underserved areas. Our findings suggest that between 1992 and 2009, HB
      vaccination in China has prevented 24 million chronic HBV infections and 4.3
      million future deaths due to cirrhosis, hepatocellular carcinoma and acute
      hepatitis. During the CGP between 2003 and 2009, an estimated 3.8 million chronic
      HBV infections and 680,000 deaths were prevented in CGP areas. We found that the
      CGP funding increased HB vaccine coverage in project areas by 4-15% for HB3 and 4
      27% for timely birth dose beyond the coverage expected without the CGP. The CGP
      represents a highly successful public health collaboration between the national
      government and international partners.

PMID- 24331024
TI  - Key outcomes and addressing remaining challenges--perspectives from a final
      evaluation of the China GAVI project.
AB  - During the China GAVI project, implemented between 2002 and 2010, more than 25
      million children received hepatitis B vaccine with the support of project, and
      the vaccine proved to be safe and effective. With careful consideration for
      project savings, China and GAVI continually adjusted the budget, additionally
      allowing the project to spend operational funds to support demonstration projects
      to improve timely birth dose (TBD), conduct training of EPI staff, and to monitor
      the project impact. Results from the final evaluation indicated the achievement
      of key outcomes. As a result of government co-investment, human resources at
      county level engaged in hepatitis B vaccination increased from 29 per county on
      average in 2002 to 66 in 2009. All project counties funded by the GAVI project
      use auto-disable syringes for hepatitis B vaccination and other vaccines.
      Surveyed hepatitis B vaccine coverage increased from 71% in 2002 to 93% in 2009
      among infants. The HBsAg prevalence declined from 9.67% in 1992 to 0.96% in 2006
      among children under 5 years of age. However, several important issues remain:
      (1) China still accounts for the largest annual number of perinatal HBV
      infections (estimated 84,121) in the WHO WPR region; (2) China still lacks a
      clear national policy for safe injection of vaccines; (3) vaccination of high
      risk adults and protection of health care workers are still not implemented; (4)
      hepatitis B surveillance needs to be refined to more accurately monitor acute
      hepatitis B; and (5) a program for treatment of persons with chronic HBV
      infection is needed. Recommendations for future hepatitis B control include:
      using the lessons learned from the China GAVI project for future introductions of
      new vaccines; addressing unmet needs with a second generation hepatitis B program
      to reach every infant, including screening mothers, and providing HBIG for
      infants born to HBsAg positive mothers; expanding vaccination to high risk
      adults; addressing remaining unsafe injection issues; and improving monitoring of
      acute hepatitis B. This paper describes findings and discusses perspectives from
      a final project evaluation, a national stratified validated cross-sectional
      survey done in October 2010. 

PMID- 24331025
TI  - Origins, design and implementation of the China GAVI project.
AB  - China received GAVI support for hepatitis B vaccination in 2001 because of high
      disease burden and strong government will to protect infants at risk. The
      China/GAVI project, implemented since 2002, was funded 50% by GAVI and 50% by the
      Government of China. The purpose of the project was to increase coverage of
      hepatitis B vaccine through a pro-poor approach targeting all counties of the 12
      Western provinces and poverty counties of the 10 Central provinces, to accelerate
      integration of hepatitis B vaccine into routine immunization, and assure
      immunization injection safety. The mechanism of internal coordination among
      multiple government entities and international cooperation was established and
      comprehensive strategies were used to improve vaccine coverage and injection
      safety. After 8 years of implementation, 193,000 health care workers in 118,316
      health care facilities participated in the project, mostly at the township
      hospitals level (55,051) and in community centres (104,547). Through the China
      GAVI project, the 85% HepB3 coverage goal was reached in 98% of GAVI China
      project counties, the 75% timely birth dose (TBD) coverage goal was reached in
      80% of GAVI project counties, and AD syringes were introduced into 100% of GAVI
      supported areas. Additionally, the GAVI project was instrumental in convincing
      the Chinese Government to sustainably introduce and fully fund HepB vaccine for
      all newborns in China. The impact of hepB vaccination on HBsAg prevalence was
      observed throughout China, as HBsAg prevalence (previously ~10%) is now less than
      1% among children under 5 years of age.

PMID- 24331026
TI  - Hepatitis B control in the World Health Organization's Western Pacific Region:
      targets, strategies, status.
AB  - WHO's Western Pacific Region has the highest rates of hepatitis B virus (HBV)
      infection in the world; most countries have >8% prevalence of HBV chronic
      infection in their adult population. In 2005, Member States of the Region adopted
      a resolution to reduce chronic hepatitis B infection prevalence to less than 2%
      among children by 2012 as an interim milestone toward a regional goal of less
      than 1% prevalence. Country commitments to hepatitis B control and successes
      represent a remarkable public health achievement by preventing over 1 million
      chronic infections and 300,000 HBV-related deaths per birth cohort. Reported here
      is a review of the process and strategies for translating this public health
      initiative into practice including such activities as setting up an Expert
      Resource Panel, developing implementation guidelines, focusing on facility births
      while supporting efforts to reach home births, providing guidance for conducting
      seroprevalence surveys, and establishing a verification process. 

PMID- 24331027
TI  - [Milk alkali syndrome associated to anorexia].

PMID- 24331028
TI  - A Meta-Analysis of Transdiagnostic Cognitive Behavioural Therapy in the Treatment
      of Child and Young Person Anxiety Disorders.
AB  - BACKGROUND: Previous meta-analyses of cognitive-behavioural therapy (CBT) for
      children and young people with anxiety disorders have not considered the efficacy
      of transdiagnostic CBT for the remission of childhood anxiety. AIM: To provide a
      meta-analysis on the efficacy of transdiagnostic CBT for children and young
      people with anxiety disorders. METHODS: The analysis included randomized
      controlled trials using transdiagnostic CBT for children and young people
      formally diagnosed with an anxiety disorder. An electronic search was conducted
      using the following databases: ASSIA, Cochrane Controlled Trials Register,
      Current Controlled Trials, Medline, PsycArticles, PsychInfo, and Web of
      Knowledge. The search terms included "anxiety disorder(s)", "anxi*", "cognitive
      behavio*, "CBT", "child*", "children", "paediatric", "adolescent(s)",
      "adolescence", "youth" and "young pe*". The studies identified from this search
      were screened against the inclusion and exclusion criteria, and 20 studies were
      identified as appropriate for inclusion in the current meta-analysis. Pre- and
      posttreatment (or control period) data were used for analysis. RESULTS: Findings
      indicated significantly greater odds of anxiety remission from pre- to
      posttreatment for those engaged in the transdiagnostic CBT intervention compared
      with those in the control group, with children in the treatment condition 9.15
      times more likely to recover from their anxiety diagnosis than children in the
      control group. Risk of bias was not correlated with study effect sizes.
      CONCLUSIONS: Transdiagnostic CBT seems effective in reducing symptoms of anxiety
      in children and young people. Further research is required to investigate the
      efficacy of CBT for children under the age of 6.

PMID- 24331029
TI  - The Percutaneous shunting in Lower Urinary Tract Obstruction (PLUTO) study and
      randomised controlled trial: evaluation of the effectiveness, cost-effectiveness
      and acceptability of percutaneous vesicoamniotic shunting for lower urinary tract
      obstruction.
AB  - BACKGROUND: Congenital lower urinary tract obstruction (LUTO) is a disease
      associated with high perinatal mortality and childhood morbidity. Fetal
      vesicoamniotic shunting (VAS) bypasses the obstruction with the potential to
      improve outcome. OBJECTIVE: To determine the effectiveness, cost-effectiveness
      and patient acceptability of VAS for fetal LUTO. DESIGN: A multicentre,
      randomised controlled trial incorporating a prospective registry, decision
      analytic health economic model and preplanned Bayesian analysis using elicited
      opinions. Patient acceptability was evaluated by interview in a qualitative
      study. SETTING: Fetal medicine departments in the UK, Ireland and the
      Netherlands. PARTICIPANTS: Pregnant women with a male singleton fetus with LUTO.
      INTERVENTIONS: In utero percutaneous VAS compared with conservative care. MAIN
      OUTCOME MEASURES: The primary outcome was survival to 28 days. Secondary outcome
      measures were survival and renal function at 1 year of age, cost of care and cost
      per additional life-year and per disability-free survival at the end of 1 year.
      RESULTS: The trial stopped early with 31 women randomised because of difficulties
      in recruitment. Of those randomised to VAS and conservative management, 3/16
      (19%) and 2/15 (13%), respectively, did not receive their allocated intervention.
      Based on intention-to-treat analysis, survival at 28 days was higher if allocated
      VAS (50%) than conservative management (27%) [relative risk (RR) 1.88, 95%
      confidence interval (CI) 0.71 to 4.96, p = 0.27]. At 12 months survival was 44%
      in the VAS arm and 20% in the conservative arm (RR 2.19, 95% CI 0.69 to 6.94, p =
      0.25). Neither difference was statistically significant. Of survivors at 1 year,
      two in the VAS arm had no evidence of renal impairment and four in the VAS arm
      and two in the conservative arm required medical management. One baby in the
      conservative arm had end-stage renal failure at 1 year. VAS was more expensive
      because of additional surgery and intensive care. VAS cost L15,500 per survivor
      at 1 year and L43,900 per disability-free year. Elicited expert opinions showed
      uncertainty in the effect of VAS at 28 days. In a Bayesian analysis combining
      elicited opinion with the results, uncertainty of the benefit of VAS remained (RR
      1.31, 95% credible interval 0.84 to 2.18). The acceptability study identified
      visualisation of the fetus during ultrasound scanning, perceiving a personal
      benefit, and altruism as positive influences on recruitment. Fear of the VAS
      procedure and the perceived severity of LUTO influenced non-participation. The
      need for more detailed information about the condition and its implications
      during pregnancy and following delivery was a further important finding of this
      research. Recruitment was hampered by logistical and regulatory difficulties, a
      lower incidence of LUTO and lower antenatal diagnosis rate [estimated to be 3.34
      (95% CI 2.95 to 3.72) per 10,000 total births and 47%, respectively, in an
      associated epidemiological study] and high termination of pregnancy rates. In the
      registry women also demonstrated a clear preference for conservative management.
      CONCLUSIONS: Survival to 28 days and 1 year appears to be higher with VAS than
      with conservative management, but it is not possible to prove benefit beyond
      reasonable doubt. Notably, prognosis in both arms for survival and renal function
      is poor. VAS was substantially more costly and unlikely to be regarded as cost
      effective based on the 1-year data. Parents should be counselled about the risks
      of pregnancy loss with or without VAS insertion. The National Institute for
      Health and Care Excellence interventional procedures guidance (IPG 202) should be
      updated to reflect this new evidence. Babies in the PLUTO trial should be
      followed up long term for the different outcomes. TRIAL REGISTRATION:
      ISRCTN53328556. FUNDING: This project was funded by the NIHR Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment ; Vol. 17, No. 59. See the NIHR Journals Library website for further
      project information.

PMID- 24331030
TI  - Osteochondritis dissecans with a large osteochondral free body in the
      posterolateral compartment of the knee: a case report.
AB  - A large osteochondral fragment trapped in the posterolateral compartment of a
      knee was removed from a posteromedial portal through the trans-septal portal and
      fixed on an osteochondral defect of the lateral femoral condyle in a 16 year-old
      boy. When a free body in the posterolateral compartment is so large that
      enlargement of the portal site is required for removal, doing so from a
      posteromedial portal is safer and easier than from a posterolateral portal.

PMID- 24331031
TI  - Serological survey of a new type of reovirus in humans in China.
AB  - To evaluate the presence of a new type of reovirus (designated R4) in humans, we
      determined the prevalence of specific antibodies using a neutralization assay and
      ELISA. The sera from 97 healthy people and 219 patients in our hospital with
      measles, hand-foot-and-mouth disease, liver diseases, and diarrhoea were
      investigated. Although the study population was limited, our data suggested that
      R4 is widespread in the human population. A significantly higher level of R4
      specific antibody in patients than in healthy people is worthy of consideration,
      since it poses a risk for aggravation of the extant illness by the reovirus.

PMID- 24331032
TI  - Air Polycyclic Aromatic Hydrocarbons (PAHs) associated with PM2.5 in a North
      Cantabric coast urban environment.
AB  - Health studies and more specifically epidemiological studies require an extended
      analysis of the physical and chemical characteristics of the environment in which
      are held. The aim of this study is to evaluate the concentration of six
      Polycyclic Aromatic Hydrocarbons (PAHs) in PM2.5 fraction of air in a peri-urban
      environment in the province of Gipuzkoa (Basque Country, Spain) where residential
      areas are surrounded by industrial activity. The six studied PAH are as follows:
      Fluoranthene, Benzo(b)fluoranthene, Benzo(k)fluoranthene, (Benzo(a)pyrene,
      Indene(123-cd)pyrene and Benzo(ghi)perylene. Our six-year study shows a decrease
      in PAH concentrations between 2006 and 2011, especially since 2008 due to the
      fall in industrial activity and related traffic. Overall, 801 data were obtained.
      Total PAH concentration ranged between 0.3 and 8.29ngm(-3) and Benzo(a)pyrene
      (BaP) from 0.05 to 0.88ngm(-3). The mean value for BaP in PM2.5 was 0.15ngm(-3)
      and the target value established by European legislation in PM10 was only
      exceeded in occasional days. Contribution percentages of each PAH in the
      monitoring sites were very similar, indicating common sources. The results of
      this study suggest that emission from industry play an important role although we
      also have to consider the contribution of traffic. PAH seasonal variations are
      similar as those reported in many previous studies. BaP and PAH concentration
      values in our region of study were in the range of other Spanish cities. 

PMID- 24331033
TI  - Polar and non-polar organic aerosols from large-scale agricultural-waste burning
      emissions in Northern India: Implications to organic mass-to-organic carbon
      ratio.
AB  - This study focuses on characteristics of organic aerosols (polar and non-polar)
      and total organic mass-to-organic carbon ratio (OM/OC) from post-harvest
      agricultural-waste (paddy- and wheat-residue) burning emissions in Northern
      India. Aerosol samples from an upwind location (Patiala: 30.2 degrees N, 76.3
      degrees E) in the Indo-Gangetic Plain were analyzed for non-polar and polar
      fractions of organic carbon (OC1 and OC2) and their respective mass (OM1 and
      OM2). On average, polar organic aerosols (OM2) contribute nearly 85% of the total
      organic mass (OM) from the paddy- and wheat-residue burning emissions. The water
      soluble-OC (WSOC) to OC2 ratio, within the analytical uncertainty, is close to 1
      from both paddy- and wheat-residue burning emissions. However, temporal
      variability and relatively low WSOC/OC2 ratio (Av: 0.67+/-0.06) is attributed to
      high moisture content and poor combustion efficiency during paddy-residue
      burning, indicating significant contribution (~30%) of aromatic carbon to OC2.
      The OM/OC ratio for non-polar (OM1/OC1~1.2) and polar organic aerosols
      (OM2/OC2~2.2), hitherto unknown for open agricultural-waste burning emissions, is
      documented in this study. The total OM/OC ratio is nearly identical, 1.9+/-0.2
      and 1.8+/-0.2, from paddy- and wheat-residue burning emissions. 

PMID- 24331034
TI  - Bioinhibitory effect of hydrogenotrophic bacteria on nitrate reduction by
      nanoscale zero-valent iron.
AB  - Hydrogenotrophic bacteria (HTB) were introduced into a nitrate removal system,
      which used nanoscale zero-valent iron (nZVI) as reductant, to investigate its
      bioinhibitory effect. Based on the results, it was noted that addition of HTB
      culture (10-50 mL) led to 58.9-91.4% decrease in the first observed rate constant
      (kobs1), which represented the nitrate removal rate by nZVI, and a reduction in
      the generated poisonous by-products from 94.9% to 38.5%. In other words, HTB had
      a significant inhibitory effect on nitrate reduction by nZVI. However, the
      pathway of this bioinhibition only prevented the occurrence of chemical
      reduction, but not competition for nitrate. Furthermore, FeOOH coating was
      observed on the surface of nZVI, instead of Fe3O4 or Fe2O3, which could prevent
      electron transmission from nZVI to nitrate. Considering that FeOOH was the
      product of iron corrosion, the result indicated that HTB could inhibit chemical
      reduction by enhancing the reaction between nZVI and water.

PMID- 24331035
TI  - Molecular mechanisms of phoxim-induced silk gland damage and TiO2 nanoparticle
      attenuated damage in Bombyx mori.
AB  - Phoxim is a useful organophosphate (OP) pesticide used in agriculture in China,
      however, exposure to this pesticide can result in a significant reduction in
      cocooning in Bombyx mori (B. mori). Titanium dioxide nanoparticles (TiO2 NPs)
      have been shown to decrease phoxim-induced toxicity in B. mori; however, very
      little is known about the molecular mechanisms of silk gland damage due to OP
      exposure and repair of gland damage by TiO2 NP pretreatment. In the present
      study, exposure to phoxim resulted in a significant reduction in cocooning rate
      in addition to silk gland damage, whereas TiO2 NP attenuated phoxim-induced gland
      damage, increased the antioxidant capacity of the gland, and increased cocooning
      rate in B. mori. Furthermore, digital gene expression data suggested that phoxim
      exposure led to significant alterations in the expression of 833 genes. In
      particular, phoxim exposure caused significant down-regulation of Fib-L, Ser2,
      Ser3, and P25 genes involved in silk protein synthesis, and up-regulation of
      SFGH, UCH3, and Salhh genes involved in silk protein hydrolysis. A combination of
      both phoxim and TiO2 NP treatment resulted in marked changes in the expression of
      754 genes, while treatment with TiO2 NPs led to significant alterations in the
      expression of 308 genes. Importantly, pretreatment with TiO2 NPs increased Fib-L,
      Ser2, Ser3, and P25 expression, and decreased SFGH, UCH3, and Salhh expression in
      silk protein in the silk gland under phoxim stress. Therefore, Fib-L, Ser2, Ser3,
      P25, SFGH, UCH3, and Salhh may be potential biomarkers of silk gland toxicity in
      B. mori caused by phoxim exposure. 

PMID- 24331036
TI  - Enhanced biodegradation of asphalt in the presence of Tween surfactants, Mn(2+)
      and H2O2 by Pestalotiopsis sp. in liquid medium and soil.
AB  - Asphalt and fractions thereof can contaminate water and soil environments.
      Forming as residues in distillation products in crude oil refineries, asphalts
      consist mostly of asphaltene instead of aliphatics, aromatics, and resins. The
      high asphaltene content might be responsible for the decrease in bioavailability
      to microorganisms and therefore reduce the biodegradability of asphalt in the
      environment. In this study, the effect on asphalt biodegradation by
      Pestalotiopsis sp. in liquid medium and soil of nonionic Tween surfactants in the
      presence of Mn2+ and H2O2 was examined. The degradation was enhanced by Tween 40
      or Tween 80 (0.1%) in the presence of Mn2+ (1 mM) and H2O2 (0.05 mM). A Tween
      surfactant, Mn2+, and H2O2 can overcome bioavailability-mediated constraints and
      increase ligninolytic activities, particularly manganese peroxidase and laccase
      activities. The study is significant for the bioremediation of asphalt and/or
      viscous-crude oil-contaminated environments.

PMID- 24331037
TI  - A novel non-invasive electrochemical biosensing device for in situ determination
      of the alcohol content in blood by monitoring ethanol in sweat.
AB  - A non-invasive, passive and simple to use skin surface based sensing device for
      determining the blood's ethanol content (BAC) by monitoring transdermal alcohol
      concentration (TAC) is designed and developed. The proposed prototype is based on
      bienzyme amperometric composite biosensors that are sensitive to the variation of
      ethanol concentration. The prototype correlates, through previous calibration set
      up, the amperometric signal generated from ethanol in sweat with its content in
      blood in a short period of time. The characteristics of this sensor device permit
      determination of the ethanol concentration in isolated and in continuous form,
      giving information of the BAC of a subject either in a given moment or its
      evolution during long periods of time (8h). Moreover, as the measurements are
      performed in a biological fluid, the evaluated individual is not able to alter
      the result of the analysis. The maximum limit of ethanol in blood allowed by
      legislation is included within the linear range of the device (0.0005-0.6 g L(
      1)). Moreover, the device shows higher sensitivity than the breathalyzers
      marketed at the moment, allowing the monitoring of the ethanol content in blood
      to be obtained just 5 min after ingestion of the alcoholic drink. The comparison
      of the obtained results using the proposed device in the analysis of 40
      volunteers with those provided by the gas chromatographic reference method for
      determination of BAC pointed out that there were no significant differences
      between both methods.

PMID- 24331038
TI  - Second- and higher-order data generation and calibration: a tutorial.
AB  - An introduction to multi-way calibration based on second- and higher-order data
      generation and processing is provided, with emphasis on practical experimental
      aspects. After a discussion concerning a proper nomenclature scheme, a suitable
      classification of the obtainable data, and the general features of the available
      algorithms and their underlying models, a series of examples is discussed in
      detail, with the purpose of illustrating the great potentiality of the field for
      the analytical community. Emphasis is directed toward the most popular multi-way
      data, i.e., second-order or matrix data, which can be conveniently measured in a
      variety of instruments. Third-order data are being increasingly studied and are
      also discussed, along with the less explored field of fourth-order data. The
      estimation of figures of merit, which analysts need to report during method
      development, is now sufficiently mature to be provided for the general audience. 

PMID- 24331039
TI  - Ion chromatography-mass spectrometry: a review of recent technologies and
      applications in forensic and environmental explosives analysis.
AB  - The development and application of ion chromatography (IC) coupled to mass
      spectrometry (MS) is discussed herein for the quantitative determination of low
      order explosives-related ionic species in environmental and forensic sample
      types. Issues relating to environmental explosives contamination and the need for
      more confirmatory IC-MS based applications in forensic science are examined. In
      particular, the compatibility of a range of IC separation modes with MS detection
      is summarised along with the analytical challenges that have been overcome to
      facilitate determinations at the ng-MUg L(-1) level. Observed trends in coupling
      IC to inductively coupled plasma and electrospray ionisation mass spectrometry
      form a particular focus. This review also includes a discussion of the relative
      performance of reported IC-MS methods in comparison to orthogonal ion separation
      based, spectrometric and spectroscopic approaches to confirmatory detection of
      low-order explosives. Finally, some promising areas for future research are
      highlighted and discussed with respect to potential IC-MS applications.

PMID- 24331040
TI  - Trends and challenges of refractometric nanoplasmonic biosensors: a review.
AB  - Motivated by potential benefits such as sensor miniaturization, multiplexing
      opportunities and higher sensitivities, refractometric nanoplasmonic biosensing
      has profiled itself in a short time span as an interesting alternative to
      conventional Surface Plasmon Resonance (SPR) biosensors. This latter conventional
      sensing concept has been subjected during the last decades to strong
      commercialization, thereby strongly leaning on well-developed thin-film surface
      chemistry protocols. Not surprisingly, the examples found in literature based on
      this sensing concept are generally characterized by extensive analytical studies
      of relevant clinical and diagnostic problems. In contrast, the more novel
      Localized Surface Plasmon Resonance (LSPR) alternative finds itself in a much
      earlier, and especially, more fundamental stage of development. Driven by new
      fabrication methodologies to create nanostructured substrates, published work
      typically focuses on the novelty of the presented material, its optical
      properties and its use - generally limited to a proof-of-concept - as a label
      free biosensing scheme. Given the different stages of development both SPR and
      LSPR sensors find themselves in, it becomes apparent that providing a comparative
      analysis of both concepts is not a trivial task. Nevertheless, in this review we
      make an effort to provide an overview that illustrates the progress booked in
      both fields during the last five years. First, we discuss the most relevant
      advances in SPR biosensing, including interesting analytical applications,
      together with different strategies that assure improvements in performance,
      throughput and/or integration. Subsequently, the remaining part of this work
      focuses on the use of nanoplasmonic sensors for real label-free biosensing
      applications. First, we discuss the motivation that serves as a driving force
      behind this research topic, together with a brief summary that comprises the main
      fabrication methodologies used in this field. Next, the sensing performance of
      LSPR sensors is examined by analyzing different parameters that can be invoked in
      order to quantitatively assess their overall sensing performance. Two aspects are
      highlighted that turn out to be especially important when trying to maximize
      their sensing performance, being (1) the targeted functionalization of the
      electromagnetic hotspots of the nanostructures, and (2) overcoming inherent
      negative influence that stem from the presence of a high refractive index
      substrate that supports the nanostructures. Next, although few in numbers, an
      overview is given of the most exhaustive and diagnostically relevant LSPR sensing
      assays that have been recently reported in literature, followed by examples that
      exploit inherent LSPR characteristics in order to create highly integrated and
      high-throughput optical biosensors. Finally, we discuss a series of
      considerations that, in our opinion, should be addressed in order to bring the
      realization of a stand-alone LSPR biosensor with competitive levels of
      sensitivity, robustness and integration (when compared to a conventional SPR
      sensor) much closer to reality. 

PMID- 24331041
TI  - Ultrasound: a subexploited tool for sample preparation in metabolomics.
AB  - Metabolomics, one of the most recently emerged "omics", has taken advantage of
      ultrasound (US) to improve sample preparation (SP) steps. The metabolomics-US
      assisted SP step binomial has experienced a dissimilar development that has
      depended on the area (vegetal or animal) and the SP step. Thus, vegetal
      metabolomics and US assisted leaching has received the greater attention
      (encompassing subdisciplines such as metallomics, xenometabolomics and, mainly,
      lipidomics), but also liquid-liquid extraction and (bio)chemical reactions in
      metabolomics have taken advantage of US energy. Also clinical and animal samples
      have benefited from US assisted SP in metabolomics studies but in a lesser
      extension. The main effects of US have been shortening of the time required for
      the given step, and/or increase of its efficiency or availability for automation;
      nevertheless, attention paid to potential degradation caused by US has been scant
      or nil. Achievements and weak points of the metabolomics-US assisted SP step
      binomial are discussed and possible solutions to the present shortcomings are
      exposed. 

PMID- 24331042
TI  - Direct determination of sodium, potassium, chromium and vanadium in biodiesel
      fuel by tungsten coil atomic emission spectrometry.
AB  - High levels of sodium and potassium can be present in biodiesel fuel and
      contribute to corrosion, reduced performance and shorter engine lifetime. On the
      other hand, trace amounts of chromium and vanadium can increase the emission of
      pollutants during biodiesel combustion. Sample viscosity, immiscibility with
      aqueous solutions and high carbon content can compromise biodiesel analyzes. In
      this work, tungsten filaments extracted from microscope light bulbs are used to
      successively decompose biodiesel's organic matrix, and atomize and excite the
      analytes to determine sodium, potassium, chromium and vanadium by tungsten coil
      atomic emission spectrometry (WCAES). No sample preparation other than simple
      dilution in methanol or ethanol is required. Direct analysis of 10-MUL sample
      aliquots using heating cycles with less than 150 s results in limits of detection
      (LOD) as low as 20, 70, 70 and 90 MUg kg(-1) for Na, K, Cr and V, respectively.
      The procedure's accuracy is checked by determining Na and K in a biodiesel
      reference sample and carrying out spike experiments for Cr and V. No
      statistically significant differences were observed between reference and
      determined values for all analytes at a 95% confidence level. The procedure was
      applied to three different biodiesel samples and concentrations between 6.08 and
      95.6 mg kg(-1) for Na and K, and between 0.22 and 0.43 mg kg(-1) for V were
      obtained. The procedure is simple, fast and environmentally friendly. Small
      volumes of reagents, samples and gases are used and no residues are generated.
      Powers of detection are comparable to other traditional methods.

PMID- 24331043
TI  - Determination of trace sulfur in biodiesel and diesel standard reference
      materials by isotope dilution sector field inductively coupled plasma mass
      spectrometry.
AB  - A method is described for quantification of sulfur at low concentrations on the
      order of mgkg(-1) in biodiesel and diesel fuels using isotope dilution and sector
      field inductively coupled plasma mass spectrometry (ID-SF-ICP-MS). Closed vessel
      microwave-assisted digestion was employed using a diluted nitric acid and
      hydrogen peroxide decomposition medium to reduce sample dilution volumes. Medium
      resolution mode was employed to eliminate isobaric interferences at (32)S and
      (34)S related to polyatomic phosphorus and oxygen species, and sulfur hydride
      species. The method outlined yielded respective limits of detection (LOD) and
      limits of quantification (LOQ) of 0.7 mg kg(-1) S and 2.5 mg kg(-1) S (in the
      sample). The LOD was constrained by instrument background counts at (32)S but was
      sufficient to facilitate value assignment of total S mass fraction in NIST SRM
      2723b Sulfur in Diesel Fuel Oil at 9.06+/-0.13 mg kg(-1). No statistically
      significant difference at a 95% confidence level was observed between the
      measured and certified values for certified reference materials NIST SRM 2773
      B100 Biodiesel (Animal-Based), CENAM DRM 272b and NIST SRM 2723a Sulfur in Diesel
      Fuel Oil, validating method accuracy.

PMID- 24331044
TI  - Determination of hafnium at the 10(-4)% level (relative to zirconium content)
      using neutron activation analysis, inductively coupled plasma mass spectrometry
      and inductively coupled plasma atomic emission spectrometry.
AB  - Hafnium at the very low level of 1-8 ppm (in relation to zirconium) was
      determined in zirconium sulfate solutions (originating from investigations of the
      separation of ca. 44 ppm Hf from zirconium by means of the ion exchange method)
      by using three independent methods: inductively coupled plasma mass spectrometry
      (ICP MS), neutron activation analysis (NAA) and inductively coupled plasma atomic
      emission spectrometry (ICP-AES). The results of NAA and ICP MS determinations
      were consistent with each other across the entire investigated range (the RSD of
      both methods did not exceed 38%). The results of ICP-AES determination were more
      diverse, particularly at less than 5 ppm Hf (RSD was significantly higher: 29
      253%). The ion exchange method exploiting Diphonix((r)) resin proved sufficient
      efficiency in Zr-Hf separation when the initial concentration ratio of the
      elements ([Zr]0/[Hf]0) ranged from 1200 to ca. 143,000.

PMID- 24331045
TI  - Development of a simple method for the determination of nitrite and nitrate in
      groundwater by high-resolution continuum source electrothermal molecular
      absorption spectrometry.
AB  - In this work, it was developed a method for the determination of nitrite and
      nitrate in groundwater by high-resolution continuum source electrothermal
      molecular absorption spectrometry of NO produced by thermal decomposition of
      nitrate in a graphite furnace. The NO line at 215.360 nm was used for all
      analytical measurements and the signal obtained by integrated absorbance of three
      pixels. A volume of 20 MUL of standard solution or groundwater sample was
      injected into graphite furnace and 5 MUL of a 1% (m/v) Ca solution was co
      injected as chemical modifier. The pyrolisis and vaporization temperatures
      established were of 150 and 1300 degrees C, respectively. Under these conditions,
      it was observed a difference of thermal stability among the two nitrogen species
      in the presence of hydrochloric acid co-injected. While that the nitrite signal
      was totally suppressed, nitrate signal remained nearly stable. This way, nitrogen
      can be quantified only as nitrate. The addition of hydrogen peroxide provided the
      oxidation of nitrite to nitrate, which allowed the total quantification of the
      species and nitrite obtained by difference. A volume of 5 MUL of 0.3% (v/v)
      hydrochloric acid was co-injected for the elimination of nitrite, whereas that
      hydrogen peroxide in the concentration of 0.75% (v/v) was added to samples or
      standards for the oxidation of nitrite to nitrate. Analytical curve was
      established using standard solution of nitrate. The method described has limits
      of detection and quantification of 0.10 and 0.33 MUg mL(-1) of nitrogen,
      respectively. The precision, estimated as relative standard deviation (RSD), was
      of 7.5 and 3.8% (n=10) for groundwater samples containing nitrate-N
      concentrations of 1.9 and 15.2 MUg mL(-1), respectively. The proposed method was
      applied to the analysis of 10 groundwater samples and the results were compared
      with those obtained by ion chromatography method. In all samples analyzed, the
      concentration of nitrite-N was always below of the limit of quantification of
      both the methods. The concentrations of nitrate-N varied from 0.58 to 15.5 MUg
      mL(-1). No significant difference it was observed between the results obtained by
      both methods for nitrate-N, at the 95% confidence level.

PMID- 24331046
TI  - Advanced recognition of explosives in traces on polymer surfaces using LIBS and
      supervised learning classifiers.
AB  - The large similarity existing in the spectral emissions collected from organic
      compounds by laser-induced breakdown spectroscopy (LIBS) is a limiting factor for
      the use of this technology in the real world. Specifically, among the most
      ambitious challenges of today's LIBS involves the recognition of an organic
      residue when neglected on the surface of an object of identical nature. Under
      these circumstances, the development of an efficient algorithm to disclose the
      minute differences within this highly complex spectral information is crucial for
      a realistic application of LIBS in countering explosive threats. An approach
      cemented on scatter plots of characteristic emission features has been developed
      to identify organic explosives when located on polymeric surfaces (teflon, nylon
      and polyethylene). By using selected spectral variables, the approach allows to
      design a concise classifier for alerting when one of four explosives (DNT, TNT,
      RDX and PETN) is present on the surface of the polymer. Ordinary products
      (butter, fuel oil, hand cream, olive oil and motor oil) cause no confusion in the
      decisions taken by the classifier. With rates of false negatives and false
      positives below 5%, results demonstrate that the classification algorithm enables
      to label residues according to their harmful nature in the most demanding
      scenario for a LIBS sensor. 

PMID- 24331047
TI  - An efficient algorithm coupled with synthetic minority over-sampling technique to
      classify imbalanced PubChem BioAssay data.
AB  - It is common that imbalanced datasets are often generated from high-throughput
      screening (HTS). For a given dataset without taking into account the imbalanced
      nature, most classification methods tend to produce high predictive accuracy for
      the majority class, but significantly poor performance for the minority class. In
      this work, an efficient algorithm, GLMBoost, coupled with Synthetic Minority Over
      sampling TEchnique (SMOTE) is developed and utilized to overcome the problem for
      several imbalanced datasets from PubChem BioAssay. By applying the proposed
      combinatorial method, those data of rare samples (active compounds), for which
      usually poor results are generated, can be detected apparently with high balanced
      accuracy (Gmean). As a comparison with GLMBoost, Random Forest (RF) combined with
      SMOTE is also adopted to classify the same datasets. Our results show that the
      former (GLMBoost+SMOTE) not only exhibits higher performance as measured by the
      percentage of correct classification for the rare samples (Sensitivity) and
      Gmean, but also demonstrates greater computational efficiency than the latter
      (RF+SMOTE). Therefore, we hope that the proposed combinatorial algorithm based on
      GLMBoost and SMOTE could be extensively used to tackle the imbalanced
      classification problem. 

PMID- 24331048
TI  - Amplified impedimetric aptasensor based on gold nanoparticles covalently bound
      graphene sheet for the picomolar detection of ochratoxin A.
AB  - An amplified electrochemical impedimetric aptasensor for ochratoxin A (OTA) was
      developed with picomolar sensitivity. A facile route to fabricate gold
      nanoparticles covalently bound reduced graphene oxide (AuNPs-rGO) resulted in a
      large number of well-dispersed AuNPs on graphene sheets with tremendous binding
      sites for DNA, since the single rGO sheet and each AuNP can be loaded with
      hundreds of DNA strands. An aptasensor with sandwich model was fabricated which
      involved thiolated capture DNA immobilized on a gold electrode to capture the
      aptamer, then the sensing interface was incubated with OTA at a desired
      concentration, followed by AuNPs-rGO functionalized reporter DNA hybridized with
      the residual aptamers. By exploiting the AuNPs-rGO as an excellent signal
      amplified platform, a single hybridization event between aptamer and reporter DNA
      was translated into more than 10(7) redox events, leading to a substantial
      increase in charge-transfer resistance (Rct) by 7~ orders of magnitude compared
      with that of the free aptamer modified electrode. Such designed aptasensor showed
      a decreased response of Rct to the increase of OTA concentrations over a wide
      range of 1 pg mL(-1)-50 ng mL(-1) and could detect extremely low OTA
      concentration, namely, 0.3 pg mL(-1) or 0.74 pM, which was much lower than that
      of most other existed impedimetric aptasensors. The signal amplification platform
      presented here would provide a promising model for the aptamer-based detection
      with a direct impedimetric method.

PMID- 24331049
TI  - Sensitive and selective electrochemical determination of quinoxaline-2-carboxylic
      acid based on bilayer of novel poly(pyrrole) functional composite using one-step
      electro-polymerization and molecularly imprinted poly(o-phenylenediamine).
AB  - A facile and efficient molecularly imprinted polymer (MIP) recognition element of
      electrochemical sensor was fabricated by directly electro-polymerizing monomer o
      phenylenediamine (oPD) in the presence of template quinoxaline-2-carboxylic acid
      (QCA), based on one-step controllable electrochemical modification of
      poly(pyrrole)-graphene oxide-binuclear phthalocyanine cobalt (II) sulphonate (PPY
      GO-BiCoPc) functional composite on glassy carbon electrode (GCE). The MIP film
      coated on PPY-GO-BiCoPc functional composite decorated GCE (MIP/PPY-GO
      BiCoPc/GCE) was presented for the first time. The synergistic effect and electro
      catalytic activity toward QCA redox of PPY-GO-BiCoPc functional composite were
      discussed using various contrast tests. Also, the effect of experimental
      variables on the current response such as, electro-polymerization cycles,
      template/monomer ratio, elution condition for template removal, pH of the
      supporting electrolyte and accumulation time, were investigated in detail. Under
      the optimized conditions, the proposed MIP sensor possessed a fast rebinding
      dynamics and an excellent recognition capacity to QCA, while the anodic current
      response of square wave voltammetry (SWV) was well-proportional to the
      concentration of QCA in the range of 1.0*10(-8)-1.0*10(-4) and 1.0*10(-4)-5.0*10(
      4) mol L(-1) with a low detection limit of 2.1 nmol L(-1). The established sensor
      was applied successfully to determine QCA in commercial pork and chicken muscle
      samples with acceptable recoveries (91.6-98.2%) and satisfactory precision (1.9
      3.5% of SD), demonstrating a promising feature for applying the MIP sensor to the
      measurement of QCA in real samples.

PMID- 24331050
TI  - Quantitation of low concentrations of polysorbates in high protein concentration
      formulations by solid phase extraction and cobalt-thiocyanate derivatization.
AB  - A spectrophotometric method was developed to quantify low polysorbate (PS) levels
      in biopharmaceutical formulations containing high protein concentrations. In the
      method, Oasis HLB solid phase extraction (SPE) cartridge was used to extract PS
      from high protein concentration formulations. After loading a sample, the
      cartridge was washed with 4M guanidine HCl and 10% (v/v) methanol, and the
      retained PS was eluted by acetonitrile. Following the evaporation of
      acetonitrile, aqueous cobalt-thiocyanate reagent was added to react with the
      polyoxyethylene oxide chain of polysorbates to form a blue colored PS
      cobaltothiocyante complex. This colored complex was then extracted into methylene
      chloride and measured spectrophotometrically at 620 nm. The method performance
      was evaluated on three products containing 30-40 mg L(-1) PS-20 and PS-80 in <=70
      g L(-1) protein formulations. The method was specific (no matrix interference
      identified in three types of protein formulations), sensitive (quantitation limit
      of 10 mg L(-1) PS) and robust with good precision (relative standard deviation
      <=6.4%) and accuracy (spike recoveries from 95% to 101%). The linear range of the
      method for both PS-20 and PS-80 was 10 to 80 mg L(-1) PS. By diluting samples
      with 6M guanidine HCl and/or using different methylene chloride volumes to
      extract the colored complexes of standards and samples, the method could
      accurately and precisely quantify 40 mg L(-1) PS in up to 300 g L(-1) protein
      formulations.

PMID- 24331051
TI  - Two highly stable and selective solid phase microextraction fibers coated with
      crown ether functionalized ionic liquids by different sol-gel reaction
      approaches.
AB  - In this work, two novel crown ether functionalized ionic liquid (FIL)-based solid
      phase microextraction (SPME) fibers were prepared by sol-gel technology using the
      synthesized 1-(trimethoxysily)propyl 3-(6'-oxo-benzo-15-crown-5 hexyl)
      imidazolium bis(trifluoromethanesulphonyl)imide
      ([TMSP(Benzo15C5)HIM][N(SO2CF3)2]) and 1-allyl-3-(6'-oxo-benzo-15-crown-5 hexyl)
      imidazolium bis(trifluoromethanesulphonyl)imide ([A(Benzo15C5)HIM][N(SO2CF3)2])
      as selective stationary phases. Owing to the introduction of trimethoxysilypropyl
      to the imidazole cation, the [TMSP(Benzo15C5)HIM][N(SO2CF3)2] could be chemically
      bonded to the formed sol-gel silica substrate through the hydrolysis and
      polycondensation reaction. Similarly, the [A(Benzo15C5)HIM][N(SO2CF3)2] was able
      to participate in the formation of the organic-inorganic copolymer coatings
      through the free radical crosslinking reaction. These two fibers were determined
      to have "bubble-like" surface characteristics analogous to a previously prepared
      [A(Benzo15C5)HIM][PF6]-based fiber. Their thermal stabilities were much higher
      than that of the [A(Benzo15C5)HIM][PF6]-based coating. They were capable of
      withstanding temperatures as high as 400 degrees C without evident loss of the
      crown ether FILs. They also had strong solvent, acid and alkali resistance, good
      coating preparation reproducibility and high selectivity for medium polar to
      polar compounds. The high selectivity of these two fibers could be attributed to
      the strong ion-dipole, hydrogen bonding and pi-pi interactions provided by the
      synergetic effect of ILs and benzo-15-crown-5 functionalities. Moreover, the
      selectivity of these two fibers was rather different although the structures of
      these two crown ether FILs were very similar. This is maybe because the relative
      contents of the crown ether FILs chemically bonded to the organic-inorganic
      copolymer coatings were quite different when prepared by different sol-gel
      reaction approaches.

PMID- 24331052
TI  - Sequential photocatalyst-assisted digestion and vapor generation device coupled
      with anion exchange chromatography and inductively coupled plasma mass
      spectrometry for speciation analysis of selenium species in biological samples.
AB  - We have developed an on-line sequential photocatalyst-assisted digestion and
      vaporization device (SPADVD), which operates through the nano-TiO2-catalyzed
      photo-oxidation and reduction of selenium (Se) species, for coupling between
      anion exchange chromatography (LC) and inductively coupled plasma mass
      spectrometry (ICP-MS) systems to provide a simple and sensitive hyphenated method
      for the speciation analysis of Se species without the need for conventional
      chemical digestion and vaporization techniques. Because our proposed on-line
      SPADVD allows both organic and inorganic Se species in the column effluent to be
      converted on-line into volatile Se products, which are then measured directly
      through ICP-MS, the complexity of the procedure and the probability of
      contamination arising from the use of additional chemicals are both low. Under
      the optimized conditions for SPADVD - using 1g of nano-TiO2 per liter, at pH 3,
      and illuminating for 80 s - we found that Se(IV), Se(VI), and selenomethionine
      (SeMet) were all converted quantitatively into volatile Se products. In addition,
      because the digestion and vaporization efficiencies of all the tested selenicals
      were improved when using our proposed on-line LC/SPADVD/ICP-MS system, the
      detection limits for Se(IV), Se(VI), and SeMet were all in the nanogram-per-liter
      range (based on 3sigma). A series of validation experiments - analysis of neat
      and spiked extracted samples - indicated that our proposed methods could be
      applied satisfactorily to the speciation analysis of organic and inorganic Se
      species in the extracts of Se-enriched supplements.

PMID- 24331053
TI  - Liquid chromatography tandem mass spectrometry determination of free and
      conjugated estrogens in breast cancer patients before and after exemestane
      treatment.
AB  - We report liquid chromatographic separation with tandem mass spectrometry
      determination of 12 endogenous estrogens and their intact conjugates in blood and
      urine and its application to study effects of exemestane treatment on estrogen
      generation and metabolism in postmenopausal women with estrogen-dependent breast
      cancer. A 0.5 mL aliquot of each urine or serum sample is fractionated with solid
      phase extraction to a fraction of free estrogen and another fraction of their
      conjugates. The reversed phase LC/MS/MS determines dansylated estrogens with
      positive ionization and intact conjugates with negative ionization. The method
      provides reproducible separation and limit of detection as low as 1 pg mL(-1) for
      free estrogens and 0.03 ng mg(-1) creatinine for the conjugates in serum and
      urine samples. The method enabled us to acquire unique concentration profiles of
      12 endogenous estrogens and their intact conjugates in 30 breast cancer patients
      before and after one month of exemestane treatment. Exemestane suppressed total
      serum and urinary estrogens by 11-97% (P<0.0001) and 8.7-91% (P<0.0001),
      respectively. Specifically, these data show that exemestane preferentially
      suppressed E1, E1-3S, E1-3G, and E2-17G more than other estrogens. Linear
      regression analysis of estrogen concentrations before and after treatment showed
      correlation coefficients of 0.8385 (n=289, P<0.0001) and 0.8863 (n=360,
      P<0.0001). This study provides urinary and blood estrogen concentration profiles
      in breast cancer patients to demonstrate the effect of exemestane on estrogen
      generation, supporting inhibition of aromatase activity.

PMID- 24331054
TI  - Validation of an in-line Raman spectroscopic method for continuous active
      pharmaceutical ingredient quantification during pharmaceutical hot-melt
      extrusion.
AB  - A calibration model for in-line API determination was developed based on Raman
      spectra collected during hot-melt extrusion. This predictive model was validated
      by calculating the accuracy profile based on the analysis results of validation
      experiments. Furthermore, based on the data of the accuracy profile, the
      measurement uncertainty was determined. Finally, the robustness of the model was
      evaluated. A Raman probe was implemented in the die of a twin-screw extruder, to
      monitor the drug concentration during extrusion of physical mixtures containing
      15, 20, 25, 30 and 35% (w/w) metoprolol tartrate (MPT) in Eudragit((r)) RS PO, an
      amorphous copolymer of acrylic and methacrylic acid esters with a low content of
      quaternary ammonium groups, which are present as salts. Several different
      calibration models for the prediction of the MPT content were developed, based on
      the use of single spectra or averaged spectra, and using partial least squares
      (PLS) regression or multivariate curve resolution (MCR). These predictive models
      were validated by extruding and monitoring mixtures containing 17.5, 22.5, 25.0,
      27.5 and 32.5% (w/w) MPT. Each validated concentration was monitored on three
      different days, by two different operators. The beta-expectation tolerance
      intervals were calculated for each model and for each of the validated MPT
      concentration levels (beta was set at 95%), and acceptance limits were set at 10%
      (relative bias), indicating that at least 95% of future measurements should not
      deviate more than 10% from the true value. The only model where these acceptance
      limits were not exceeded was the MCR model based on averaged Raman spectra. The
      uncertainty measurements for this model showed that the unknown true value can be
      found at a maximum of +/-7.00% around the measured result, with a confidence
      level of 95%. The robustness of this model was evaluated via an experimental
      design varying throughput, screw speed and barrel temperature. The robustness
      designs showed no significant influence of any of the process settings on the
      predicted concentration values. Raman spectroscopy proved to be a fast, non
      destructive and reliable method for the quantification of MPT during hot-melt
      extrusion. From the accuracy profile of the MCR model based on averaged spectra,
      it was concluded that for each MPT concentration in the validated concentration
      range, 95 out 100 future routine measurements will be included within the
      acceptance limits (10%). 

PMID- 24331055
TI  - Silver overlayer-modified surface-enhanced Raman scattering-active gold
      substrates for potential applications in trace detection of biochemical species.
AB  - Because Ag and Au nanoparticles (NPs) possess well-defined localized surface
      plasmon resonance (LSPR) they are popularly employed in the studies of surface
      enhanced Raman scattering (SERS). As shown in the literature and in our previous
      studies, the advantage of SERS-active Ag NPs is their higher SERS enhancement
      over Au NPs. On the other hand, the disadvantage of SERS-active Ag NPs compared
      to Au NPs is their serious decay of SERS enhancement in ambient laboratory air.
      In this work, we develop a new strategy for preparing highly SERS-active Ag NPs
      deposited on a roughened Au substrate. This strategy is derived from the
      modification of electrochemical underpotential deposition (UPD) of metals. The
      coverage of Ag NPs on the roughened Au substrate can be as high as 0.95.
      Experimental results indicate that the SERS of Rhodamine 6G (R6G) observed on
      this developed substrate exhibits a higher intensity by ca. 50-fold of magnitude,
      as compared with that of R6G observed on the substrate without the deposition of
      Ag NPs. The limit of detection (LOD) for R6G measured on this substrate is
      markedly reduced to 2*10(-15)M. Moreover, aging of SERS effect observed on this
      developed substrate is significantly depressed, as compared with that observed on
      a generally prepared SERS-active Ag substrate. These aging tests were performed
      in an atmosphere of 50% relative humidity (RH) and 20% (v/v) O2 at 30 degrees C
      for 60 day. Also, the developed SERS-active substrate enables it practically
      applicable in the trace detection of monosodium urate (MSU)-containing solution
      in gouty arthritis without a further purification process. 

PMID- 24331056
TI  - New competitive dendrimer-based and highly selective immunosensor for
      determination of atrazine in environmental, feed and food samples: the importance
      of antibody selectivity for discrimination among related triazinic metabolites.
AB  - A new voltammetric competitive immunosensor selective for atrazine, based on the
      immobilization of a conjugate atrazine-bovine serum albumine on a nanostructured
      gold substrate previously functionalized with poliamidoaminic dendrimers, was
      realized, characterized, and validated in different real samples of environmental
      and food concern. Response of the sensor was reliable, highly selective and
      suitable for the detection and quantification of atrazine at trace levels in
      complex matrices such as territorial waters, corn-cultivated soils, corn
      containing poultry and bovine feeds and corn flakes for human use. Selectivity
      studies were focused on desethylatrazine, the principal metabolite generated by
      long-term microbiological degradation of atrazine, terbutylazine-2-hydroxy and
      simazine as potential interferents. The response of the developed immunosensor
      for atrazine was explored over the 10(-2)-10(3) ng mL(-1) range. Good sensitivity
      was proved, as limit of detection and limit of quantitation of 1.2 and 5 ng mL(
      1), respectively, were estimated for atrazine. RSD values <5% over the entire
      explored range attested a good precision of the device.

PMID- 24331057
TI  - Label-free amperometric immunosensor based on prussian blue as artificial
      peroxidase for the detection of methamphetamine.
AB  - A label-free amperometric immunosensor for the detection of methamphetamine was
      developed. The prussian blue deposited/l-cystine-modified electrode was covered
      with nano-Au/(3-mercaptorpropyl) trime-thoxysilane film. Then, the nano-Au was
      used for the immunosensor platform to capture a large amount of anti
      methamphetamine. PB exhibited excellent electrocatalytical properties toward the
      reduction of H2O2 at low overpotentia to amplify the amperometric signal, which
      enhanced the sensitivity of the immunosensor. The active sites of PB could be
      shielded and the access of H2O2 from solution to the electrode might be partially
      blocked after the completion of immunoassay, led to a linear decrease in the
      response current of the electrode over the range from 1.0*10(-8) to 5.0*10(-6)
      mol L(-1)of MA. The obtained immunosensor displayed excellent catalytic reduction
      toward H2O2 due to high activity and selectivity of PB. The influence of relevant
      experimental variables, including the construction of immunosensor platform, the
      amount of MPS and the time of immunoaction, was examined and optimized.

PMID- 24331058
TI  - Lung function impairment in women aged over 40 years: The critical role of
      abdominal obesity.
AB  - SUMMARY: It is known that obesity causes to impairment of pulmonary functions.
      This impairment worsens with aging. There are studies about obesity showing that
      the uses of abdominal measurements instead of BMI are more accurate.: PURPOSE:
      The aim of our study is to investigate the correlation of waist circumference in
      the women aged over 40 years with obesity to the respiratory function tests and
      chest expansion. MATERIALS AND METHODS: In our study, BMI, waist circumference
      and chest expansion of 64 women over 40-year old were measured and the values
      obtained were compared with the results of respiratory function tests. RESULTS:
      There was a positive correlation between the age of the patients with waist
      circumference and DLCO/VA. A negative correlation was found between the age and
      MVV. The weight increase was associated with an increase in waist circumference
      and DLCO/VA. It was observed that waist circumference and DLCO/VA were increased
      and chest expansion was decreased when BMI was increased. A positive correlation
      was determined between MVV and the other respiratory function parameters, FEV1,
      FVC, FEV1/FVC and FIVC (p < 0.01). Similarly, the increase in DLCO was found to
      be correlated with the values of FEV1, FVC and FIVC. FIVC was correlated only
      with FEV1 and FVC. CONCLUSION: In this study, it was observed that respiratory
      function tests of women over 40-year old with obesity were associated with
      anthropometric measurements. But, studies with larger sample sizes and
      prospective studies are needed to provide more accurate information about the
      importance of DLCO/VA for the assessment of pulmonary function in obese women.

PMID- 24331059
TI  - BMI misclassification, leptin, C-reactive protein, and interleukin-6 in young
      women with differing levels of lean and fat mass.
AB  - SUMMARY:  OBJECTIVE: To describe the misclassification of obesity based on BMI
      criteria, in women with similar fat mass but differing lean mass levels, and to
      describe how the misclassification relates to circulating serum leptin, high
      sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6). DESIGN: Cross
      sectional study. SUBJECTS: Healthy women aged 18-35 (n = 255). MEASUREMENTS: Body
      fat was measured by dual X-ray absorptiometry (DXA). Obesity was defined using
      WHO cut-off points for BMI and body fat % (BF%) >=35. Participants were grouped
      as: (1) high fat mass/high lean mass, (2) high fat mass/low lean mass, (3) low
      fat mass/high lean mass, and (4) low fat mass/low lean mass. Serum leptin, hsCRP
      and IL-6 were assayed using commercial kits. RESULTS: According to BMI, 18.8.5%
      of the subjects (n = 48) were overweight and 13.7 (n = 35) were obese; in
      contrast, according to BF%, 48.6% (n = 124) were obese. While, the BF% of the
      high-fat groups was virtually identical (at 42.7% [sd = 7.0] and 41.8% [sd =
      4.2], respectively), the BMI of the high fat/high lean group was significantly
      greater than that of the high fat low/low lean group (30.0 +/- 5.2 and 24.9 +/-
      1.9, respectively). Leptin, hsCRP and IL-6 concentrations in the high-fat groups
      were not significantly different from each other, but were significantly greater
      than in the low-fat groups. CONCLUSIONS: BMI underestimates obesity in young
      women; misclassifying women with high fat mass and low lean mass as 'normal' when
      BF%, leptin, hsCRP and IL-6 suggest they are obese.

PMID- 24331060
TI  - Telmisartan suppresses food intake in mice via the melanocortin pathway.
AB  - SUMMARY: Telmisartan, an angiotensin type 1 receptor blocker, is widely used for
      the treatment of hypertension and related cardiovascular and organ damage. We
      here describe the effects of telmisartan on food intake and body weight using
      C57BL/6N mice, KKAy mice that overexpress agouti protein (a mouse model of type 2
      diabetes with obesity), and mice deficient for angiotensin II-1a receptor.
      Telmisartan combined with a high-fat diet significantly reduced food intake and
      body weight gain in the three groups of mice compared with respective control
      animals that were fed the high-fat diet without telmisartan. Telmisartan did not
      induce taste aversion or affect energy expenditure. Intracerebroventricular
      administration of agouti-related protein, a potent antagonist of the melanocortin
      3 receptor (MC3-R) and melanocortin 4 receptor (MC4-R), did not stimulate feeding
      in telmisartan-treated mice. Telmisartan administration enhanced the alpha
      melanocyte stimulating hormone-induced suppression of food intake. This study
      highlights a potential role for telmisartan in hypothalamic feeding regulation,
      including melanocortin receptors-mediated suppression of food intake and body
      weight gain.:

PMID- 24331061
TI  - Hyperthyrotropinemia in relation to endothelial dysfunction in obese adolescents.
AB  - SUMMARY:  BACKGROUND: It has been shown that isolated elevation of thyroid
      stimulating hormone (hyperthyrotropinemia) is quite frequent in obese
      adolescents, but it is not clear whether this condition entails an increased risk
      related to body mass index (BMI). AIM: The aim of the current study was to
      investigate the relationship between hyperthyrotropinemia and endothelial
      dysfunction and other cardiovascular risk factors in obese adolescents. METHODS:
      Seventeen obese adolescents with hyperthyrotropinemia (TSH >= 4.2 MUUI/ml) (group
      1), 21 obese adolescents with normal thyroid stimulating hormone (TSH) level
      (group 2) and 10 age- and sex-matched healthy lean controls were included in the
      study. Fasting blood glucose (FBG), lipid profile, insulin resistance (HOMA-IR)
      and thyroid hormones were determined. All participants were subjected to
      ultrasound recording of brachial artery diameter at rest and after reactive
      hyperemia (FMD) for assessment of endothelial function. RESULTS: BMI and free
      triiodothyronine (fT3) levels were higher in obese adolescents with
      hyperthyrotropinemia (group 1) than in those with normal TSH (group 2) (p <
      0.05), but there were no significant differences between the two groups in other
      metabolic parameters (lipid profile and HOMA-IR). The FMD was significantly low
      in obese adolescents (groups 1 and 2) relative to controls (3.4 +/- 18% in group
      1 and 3.6 +/- 2.2% in group 2 vs. 10.4 +/- 3.1% in control subjects), but there
      was no statistical difference between obese adolescents with hyperthyrotropinemia
      (group 1) and those with normal TSH (group 2). There were positive correlations
      between TSH and BMI (p = 0.03) and between fT3 and BMI (p = 0.04), but no
      correlation between TSH and lipid profile, HOMA-IR or FMD. CONCLUSIONS:
      Hyperthyrotropinemia is not related to endothelial dysfunction or metabolic risk
      factors in obese adolescents.

PMID- 24331062
TI  - Influence of beta 3-adrenergic receptor Trp64Arg polymorphism on the improvement
      of metabolic syndrome by exercise-based intervention in Japanese middle-aged
      males.
AB  - SUMMARY:  OBJECTIVES: To date, there have been few intervention studies
      concerning the association of metabolic syndrome with beta 3-adrenergic receptor
      (ADRB3) Trp64Arg polymorphism, although ADRB3 Trp64Arg polymorphism has been
      reported to be associated with weight gain and insulin resistance by several
      intervention programs. We examined the influence of ADRB3 Trp64Arg polymorphism
      on the improvement of metabolic syndrome by an exercise-based intervention
      program. METHODS: Thirty-six male employees who satisfied the metabolic syndrome
      criteria participated in a three-month exercise-based intervention program
      (average age, 49 +/- 6 years old). The improvement rate of metabolic syndrome
      after the intervention was compared between subjects with and without ADRB3
      Trp64Arg polymorphism. The Mantel-Haenszel test was employed to adjust the age,
      diet, and exercise in analysis of the influence of ADRB3 Trp64Arg polymorphism on
      metabolic syndrome. The Trp64Arg genotype of the beta3-adrenoceptor gene was
      examined in peripheral blood leukocyte DNA by TaqMan PCR assay. RESULTS: The
      distribution of polymorphism was 23 (Trp/Trp), 13 (Trp/Arg), and 0 (Arg/Arg). The
      metabolic syndrome improvement rates after intervention were 21.7% (Trp/Trp) and
      53.8% (Trp/Arg) (p = 0.050). After adjustment individually for age, calorie
      limitation, and 10,000 or more and 12,000 or more steps of walking per day during
      intervention, the odds ratios of the Trp/Arg genotype for improvement of
      metabolic syndrome relative to that of the Trp/Trp genotype were 5.1 (p = 0.043),
      4.9 (p = 0.051), 3.7 (p = 0.074), and 5.0 (p = 0.045), respectively. CONCLUSION:
      The results suggested that ADRB3 Trp64Arg polymorphism influences the metabolic
      syndrome improvement rate by exercise-based intervention program.

PMID- 24331063
TI  - Sex differences in energy metabolism in pre-pubescent, early pubescent and adult
      rats.
AB  - SUMMARY:  OBJECTIVE: This study was intended to investigate sex differences in
      response to a high fat (HF) diet at three stages, pre-puberty, early puberty, and
      adulthood. METHODS: Body weight, energy intake, glucose, insulin, and leptin
      concentrations were measured in male and female rats that were fed either a HF or
      a control chow during each stage of development. The sex hormones of adult rats
      were also examined. In addition, metabolic factors of male rats pair-fed with
      females were evaluated. RESULTS: At pre-puberty, the average body weight of pups
      born to a HF dam exceeded that of the control, whereas there were no significant
      differences in body weight between males and females. During early puberty and
      among 15-wk-old rats, males exhibited greater weight gain with higher energy
      intake than did females. During all three stages, HF rats exhibited significant
      increases in body weight, insulin and leptin concentrations. Estradiol levels of
      females were higher than those of males, and those of the HF groups were
      significantly lower than the control groups. Although the body weight gain in
      male rats pair-fed with females exceeded that of the females, the insulin and
      leptin levels of pair-fed HF males decreased to the control levels. CONCLUSION:
      HF male rats became obese earlier than HF females. This result may be the result
      of differences in estradiol levels between males and females. The decline of
      insulin and leptin levels in pair-fed male groups indicates that caloric
      restriction among male rats could reduce the incidence of metabolic diseases.

PMID- 24331064
TI  - Intrahepatic lipid content is linked to insulin resistance in obese subjects.
AB  - SUMMARY:  BACKGROUND: Abdominal visceral fat (VAT) and intrahepatic lipid (IHL)
      are associated with insulin resistance in obese subjects, but VAT is usually
      measured on CT scans at the umbilical level or on MRI images of the partial
      abdomen. Thus, the association of the total abdominal visceral fat volume (VFV)
      with insulin resistance is unclear. In this study, we evaluated the correlations
      of obesity-related factors, including VFV and IHL, with clinical markers of
      insulin resistance (HOMA-R and the MATSUDA Index), and then assessed the effect
      of weight loss on these factors and markers. METHODS: The study population
      consisted of 30 obese Japanese subjects with a BMI > 25 kg/m(2) (13 men and 17
      women) who underwent a 75-g oral glucose tolerance test to calculate HOMA-R and
      the MATSUDA Index, dual energy X-ray absorptiometry (DEXA) for measurement of
      body fat (%-Fat), proton magnetic resonance spectroscopy ((1)H MRS) to assess
      IHL, and whole abdominal CT scanning (from the top of the liver to the floor of
      the pelvic cavity = about 700 slices) to determine the total abdominal
      subcutaneous fat volume (SFV) and VFV. Seven subjects from the original
      population were placed on a diet and exercise program, and these indices were
      examined again after 5% reduction of body weight. RESULTS: Abdominal SFV, VFV,
      and IHL were mutually independent, but BMI and %-Fat were not independent of the
      other factors. According to multiple regression analysis, IHL (but not SFV or
      VFV) was significantly correlated with both HOMA-R and the MATSUDA Index in obese
      patients. Weight reduction by 5% led to improvement of the MATSUDA Index and
      decreased the number of subjects with metabolic syndrome, and the reduction of
      IHL was greater than that of SFV or VFV. These results suggest that IHL may be a
      superior marker of insulin resistance.

PMID- 24331065
TI  - Relationship between alcohol consumption and metabolic syndrome in Japanese men
      with overweight or obesity.
AB  - SUMMARY:  OBJECTIVE: The aim of this study was to determine the relationship of
      alcohol intake with metabolic syndrome in obese people. METHODS: Japanese men (35
      65 years, n = 7250) who showed high body mass index (25 kg/m(2) or over) were
      divided into four groups by alcohol intake [non-, light (<22 g ethanol/day),
      heavy (>=22 and <44 g ethanol/day) and very heavy (>= 44 g ethanol/day)
      drinkers]. Odds ratios for metabolic syndrome were calculated after adjustment
      for age and history of smoking. RESULTS: Prevalence of metabolic syndrome was
      significantly higher in very heavy drinkers than in nondrinkers and was
      significantly lower in light drinkers than in heavy and very heavy drinkers. The
      odds ratio vs. nondrinkers for metabolic syndrome was significantly low in light
      drinkers (odds ratio [OR] = 0.84, 95% confidence interval [CI]: 0.71-0.98, p <
      0.05), was not significant in heavy drinkers (OR = 1.01, 95% CI: 0.90-1.13), and
      was significantly high in very heavy drinkers (OR = 1.23, 95% CI: 1.08-1.40, p <
      0.01). CONCLUSIONS: In Japanese men with overweight or obesity, there are
      significant inverse and positive associations of light and excessive alcohol
      consumption, respectively, with metabolic syndrome.

PMID- 24331066
TI  - Relationships between body fat accumulation, aerobic capacity and insulin
      resistance in Japanese participants.
AB  - SUMMARY:  AIM: This study evaluated the relationships between body fat
      accumulation, aerobic capacity and insulin resistance (HOMA-IR) in 61 Japanese
      participants. METHOD: The participants were middle-aged to elderly (age: 33-73;
      BMI: 21.6-38.5). Body fat mass (FM) was evaluated by hydrostatic weighing.
      Computed tomography was used to evaluate visceral and subcutaneous fat areas (VFA
      and SFA), liver to spleen ratio (L/S), and low-density muscle area (LDMA). To
      assess aerobic capacity, VO2 at the lactate threshold (VO2@LT) and VO2 peak were
      measured using a bicycle ergometer. RESULTS: FM, VFA, SFA, LDMA and L/S
      significantly correlated with HOMA-IR, but VO2@LT and VO2 peak did not. Analysis
      of covariance after adjustment for VFA or other body fat distribution and aerobic
      capacity showed that HOMA-IR had a significant linear trend across the tertile
      groups of L/S. However, for FM, VFA, SFA, LDMA and VO2@LT or VO2 peak, no
      significant trend was observed between the tertiles and insulin resistance.
      CONCLUSIONS: Ectopic fat deposition in the liver may influence insulin resistance
      independently of other body fat accumulation and aerobic capacity in Japanese
      participants.

PMID- 24331067
TI  - Minute-by-minute stepping rate of daily physical activity in normal and
      overweight/obese adults.
AB  - SUMMARY: The relationship between minute-by-minute stepping rate under free
      living and obesity remains unclear. The purpose of the present investigation was
      to compare the levels of physical activity (PA) based on the minute-by-minute
      stepping rate under free-living conditions between normal weight (NW) and
      overweight and obese (OV) individuals. A total 40 volunteers participated in the
      present investigation. These participants were divided into NW or OV according to
      the body mass index (<25 kg m(-2) or 25 kg m(-2)). All participants wore a
      pedometer with a uni-axial accelerometer (Lifecorder-EX 4sec, Kenz, Japan) for 7
      days continuously. The Lifecorder determined the number of steps and time spent
      in PA at <100, 100-129, 130 steps min(-1) according to the minute-by-minute
      stepping rate. The OV group took a significantly fewer number of steps per day in
      comparison to that in the NW group (p < 0.05). The average daily stepping rate
      was significantly lower in the OV group in comparison to that in the NW group (p
      = 0.01). Furthermore, the OV group spent a significantly shorter time in PA at a
      100 steps min(-1) of the stepping rate compared with that in the NW group (p <
      0.05). These results indicate that obese individuals spent significantly shorter
      time in PA at 100 steps min(-1) of stepping rate in comparison to the NW
      individuals.:

PMID- 24331068
TI  - Preface to supplement. Active surveillance of vaccine safety in the US Food and
      Drug Administration's Mini-Sentinel program: identification of exposures and
      outcomes.

PMID- 24331069
TI  - A systematic review of validated methods to capture acute bronchospasm using
      administrative or claims data.
AB  - PURPOSE: To identify and assess billing, procedural, or diagnosis code, or
      pharmacy claim-based algorithms used to identify acute bronchospasm in
      administrative and claims databases. METHODS: We searched the MEDLINE database
      from 1991 to September 2012 using controlled vocabulary and key terms related to
      bronchospasm, wheeze and acute asthma. We also searched the reference lists of
      included studies. Two investigators independently assessed the full text of
      studies against pre-determined inclusion criteria. Two reviewers independently
      extracted data regarding participant and algorithm characteristics. RESULTS: Our
      searches identified 677 citations of which 38 met our inclusion criteria. In
      these 38 studies, the most commonly used ICD-9 code was 493.x. Only 3 studies
      reported any validation methods for the identification of bronchospasm, wheeze or
      acute asthma in administrative and claims databases; all were among pediatric
      populations and only 2 offered any validation statistics. Some of the outcome
      definitions utilized were heterogeneous and included other disease based
      diagnoses, such as bronchiolitis and pneumonia, which are typically of an
      infectious etiology. One study offered the validation of algorithms utilizing
      Emergency Department triage chief complaint codes to diagnose acute asthma
      exacerbations with ICD-9 786.07 (wheezing) revealing the highest sensitivity
      (56%), specificity (97%), PPV (93.5%) and NPV (76%). CONCLUSIONS: There is a
      paucity of studies reporting rigorous methods to validate algorithms for the
      identification of bronchospasm in administrative data. The scant validated data
      available are limited in their generalizability to broad-based populations.

PMID- 24331070
TI  - Methods for systematic reviews of administrative database studies capturing
      health outcomes of interest.
AB  - This report provides an overview of methods used to conduct systematic reviews
      for the US Food and Drug Administration (FDA) Mini-Sentinel project, which is
      designed to inform the development of safety monitoring tools for FDA-regulated
      products including vaccines. The objective of these reviews was to summarize the
      literature describing algorithms (e.g., diagnosis or procedure codes) to identify
      health outcomes in administrative and claims data. A particular focus was the
      validity of the algorithms when compared to reference standards such as diagnoses
      in medical records. The overarching goal was to identify algorithms that can
      accurately identify the health outcomes for safety surveillance. We searched the
      MEDLINE database via PubMed and required dual review of full text articles and of
      data extracted from studies. We also extracted data on each study's methods for
      case validation. We reviewed over 5600 abstracts/full text studies across 15
      health outcomes of interest. Nearly 260 studies met our initial criteria
      (conducted in the US or Canada, used an administrative database, reported case
      finding algorithm). Few studies (N=45), however, reported validation of case
      finding algorithms (sensitivity, specificity, positive or negative predictive
      value). Among these, the most common approach to validation was to calculate
      positive predictive values, based on a review of medical records as the reference
      standard. Of the studies reporting validation, the ease with which a given
      clinical condition could be identified in administrative records varied
      substantially, both by the clinical condition and by other factors such as the
      clinical setting, which relates to the disease prevalence. 

PMID- 24331071
TI  - A systematic review of validated methods to capture several rare conditions using
      administrative or claims data.
AB  - PURPOSE: To identify and assess billing, procedural, or diagnosis code, or
      pharmacy claim-based algorithms used to identify the following health outcomes in
      administrative and claims databases: acute disseminated encephalomyelitis (ADEM),
      optic neuritis, tics, and Henoch Schonlein purpura (HSP). METHODS: We searched
      the MEDLINE database from 1991 to September 2012 using controlled vocabulary and
      key terms related to the conditions. We also searched the reference lists of
      included studies. Two investigators independently assessed the full text of
      studies against pre-determined inclusion criteria and extracted case validation
      data from those studies meeting inclusion criteria. RESULTS: Two eligible studies
      addressed ADEM, two addressed optic neuritis, and four studies addressed tics.
      Only one study addressed HSP. Among these, one study of ADEM reported a positive
      predictive value of 66%, however the identification algorithm contained a
      combination of International Classification of Diseases (ICD) codes and other
      identification methods and the performance of the ICD-9 codes alone was not
      reported. No other studies reported validation data. CONCLUSIONS: The lack of
      data on the validity of algorithms to identify these conditions may hamper our
      ability to determine incidence patterns with respect to infection and vaccination
      exposures. Further epidemiologic research to define validated methods of
      identifying cases could improve surveillance using large linked healthcare
      databases.

PMID- 24331072
TI  - A systematic review of validated methods for identifying Kawasaki disease using
      administrative or claims data.
AB  - PURPOSE: To identify and assess algorithms used to identify Kawasaki
      syndrome/Kawasaki disease in administrative and claims databases. METHODS: We
      searched the MEDLINE database from 1991 to September 2012 using controlled
      vocabulary and key terms related to Kawasaki disease. We also searched the
      reference lists of included studies. Two investigators independently assessed the
      full text of studies against pre-determined inclusion criteria. Two reviewers
      independently extracted data regarding participant and algorithm characteristics.
      RESULTS: Our searches identified 177 citations of which 22 met our inclusion
      criteria. All studies used algorithms including International Classification of
      Diseases, Ninth Revision (ICD-9) code 446.1 either alone, or with evidence of
      intravenous immunoglobulin (IVIG) administration, or with ICD-10 code M30.3. Six
      studies confirmed diagnoses by medical chart review. Three of these six studies
      reported validation statistics, with positive predictive values of 74%, 84%, and
      86%, respectively. CONCLUSIONS: All studies that reported algorithms used either
      the ICD-9 code 446.1 either alone, with evidence of IVIG administration or with
      ICD-10 code M30.3. The ICD-9 code 446.1 alone produced positive predictive values
      of 74%, 84%, and 86% in separate studies in Georgia and California. The
      sensitivity of these codes to detect Kawasaki disease is unknown, as no sampling
      of medical records for missed true cases of Kawasaki disease was done. Further
      research would be helpful to determine whether the relatively high positive
      predictive values found in southern California are seen elsewhere and also to
      evaluate the performance of other codes to identify cases of Kawasaki disease and
      the sensitivity of the narrow algorithms that have been used to date.

PMID- 24331073
TI  - A systematic review of validated methods to capture myopericarditis using
      administrative or claims data.
AB  - PURPOSE: To identify algorithms that can capture incident cases of myocarditis
      and pericarditis in administrative and claims databases; these algorithms can
      eventually be used to identify cardiac inflammatory adverse events following
      vaccine administration. METHODS: We searched MEDLINE from 1991 to September 2012
      using controlled vocabulary and key terms related to myocarditis. We also
      searched the reference lists of included studies. Two investigators independently
      assessed the full text of studies against pre-determined inclusion criteria. Two
      reviewers independently extracted data regarding participant and algorithm
      characteristics as well as study conduct. RESULTS: Nine publications (including
      one study reported in two publications) met criteria for inclusion. Two studies
      performed medical record review in order to confirm that these coding algorithms
      actually captured patients with the disease of interest. One of these studies
      identified five potential cases, none of which were confirmed as acute
      myocarditis upon review. The other study, which employed a search algorithm based
      on diagnostic surveillance (using ICD-9 codes 420.90, 420.99, 422.90, 422.91 and
      429.0) and sentinel reporting, identified 59 clinically confirmed cases of
      myopericarditis among 492,671 United States military service personnel who
      received smallpox vaccine between 2002 and 2003. Neither study provided algorithm
      validation statistics (positive predictive value, sensitivity, or specificity).
      CONCLUSIONS: A validated search algorithm is currently unavailable for
      identifying incident cases of pericarditis or myocarditis. Several authors have
      published unvalidated ICD-9-based search algorithms that appear to capture
      myocarditis events occurring in the context of other underlying cardiac or
      autoimmune conditions.

PMID- 24331074
TI  - A systematic review of validated methods for identifying patients with rheumatoid
      arthritis using administrative or claims data.
AB  - PURPOSE: To review the evidence supporting the validity of billing, procedural,
      or diagnosis code, or pharmacy claim-based algorithms used to identify patients
      with rheumatoid arthritis (RA) in administrative and claim databases. METHODS: We
      searched the MEDLINE database from 1991 to September 2012 using controlled
      vocabulary and key terms related to RA and reference lists of included studies
      were searched. Two investigators independently assessed the full text of studies
      against pre-determined inclusion criteria and extracted the data. Data collected
      included participant and algorithm characteristics. RESULTS: Nine studies
      reported validation of computer algorithms based on International Classification
      of Diseases (ICD) codes with or without free-text, medication use, laboratory
      data and the need for a diagnosis by a rheumatologist. These studies yielded
      positive predictive values (PPV) ranging from 34 to 97% to identify patients with
      RA. Higher PPVs were obtained with the use of at least two ICD and/or procedure
      codes (ICD-9 code 714 and others), the requirement of a prescription of a
      medication used to treat RA, or requirement of participation of a rheumatologist
      in patient care. For example, the PPV increased from 66 to 97% when the use of
      disease-modifying antirheumatic drugs and the presence of a positive rheumatoid
      factor were required. CONCLUSIONS: There have been substantial efforts to propose
      and validate algorithms to identify patients with RA in automated databases.
      Algorithms that include more than one code and incorporate medications or
      laboratory data and/or required a diagnosis by a rheumatologist may increase the
      PPV.

PMID- 24331075
TI  - A systematic review of validated methods for identifying systemic lupus
      erythematosus (SLE) using administrative or claims data.
AB  - PURPOSE: To examine the validity of billing, procedural, or diagnosis code, or
      pharmacy claim-based algorithms used to identify patients with systemic lupus
      erythematosus (SLE) in administrative and claims databases. METHODS: We searched
      the MEDLINE database from 1991 to September 2012 using controlled vocabulary and
      key terms related to SLE. We also searched the reference lists of included
      studies. Two investigators independently assessed the full text of studies
      against pre-determined inclusion criteria. The two reviewers independently
      extracted data regarding participant and algorithm characteristics and assessed a
      study's methodologic rigor using a pre-defined approach. RESULTS: Twelve studies
      included validation statistics for the identification of SLE in administrative
      and claims databases. Seven of these studies used the ICD-9 code of 710.0 in
      selected populations of patients seen by a rheumatologist or patients who had
      experienced the complication of SLE-associated nephritis, other kidney disease,
      or pregnancy. The other studies looked at limited data in general populations.
      The algorithm in the selected populations had a positive predictive value (PPV)
      in the range of 70-90% and of the limited data in general populations it was in
      the range of 50-60%. CONCLUSIONS: Few studies use rigorous methods to validate an
      algorithm for the identification of SLE in general populations. Algorithms
      including ICD-9 code of 710.0 in physician billing and hospitalization records
      have a PPV of approximately 60%. A requirement that the code is obtained from a
      record based on treatment by a rheumatologist increases the PPV of the algorithm
      but limits the generalizability in the general population.

PMID- 24331076
TI  - A systematic review of validated methods for identifying Bell's palsy using
      administrative or claims data.
AB  - PURPOSE: To identify and assess billing, procedural, or diagnosis code, or
      pharmacy claims-based algorithms used to identify Bell's palsy in administrative
      and claims databases. METHODS: We searched the MEDLINE database via PubMed from
      1991 to September 2012 using controlled vocabulary and key terms related to
      Bell's palsy. We also searched the reference lists of included studies. Two
      investigators independently assessed the full text of studies against pre
      determined inclusion criteria. Two reviewers independently extracted data
      regarding participant and algorithm characteristics and assessed a study's
      methodologic rigor. RESULTS: One study identified Bell's palsy using an algorithm
      that included ICD-9 code 351.x and H-ICDA code 350.x, and two other studies
      analyzed a dataset for ICD-9 code 351.0. The positive predictive values of these
      studies were 0.81 and 0.88, based on case adjudication of ICD-9 matches. Two
      further studies calculated incidence rates without validation of their methods,
      also including ICD-9 code 351.0. No study reported the sensitivity of algorithms
      to identify Bell's palsy. CONCLUSIONS: Few publications used rigorous methods to
      identify a validated algorithm that could identify cases of Bell's palsy from an
      administrative database. The best evidence from two different datasets in the
      literature addressed in this review used ICD-9 code 351.0 or a collection of ICD
      9 codes 351.x for facial nerve disorders including Bell's palsy, along with other
      ICD-9 and H-ICDA codes for facial weakness. Each study had acceptable PPV,
      suggesting that ICD-9 based-algorithms have some utility in detecting Bell's
      palsy cases.

PMID- 24331077
TI  - A systematic review of validated methods to capture stillbirth and spontaneous
      abortion using administrative or claims data.
AB  - PURPOSE: To identify and assess diagnosis, procedure and pharmacy dispensing
      codes used to identify stillbirths and spontaneous abortion in administrative and
      claims databases from the United States or Canada. METHODS: We searched the
      MEDLINE database from 1991 to September 2012 using controlled vocabulary and key
      terms related to stillbirth or spontaneous abortion. We also searched the
      reference lists of included studies. Two investigators independently assessed the
      full text of studies against pre-determined inclusion criteria. Two reviewers
      independently extracted data regarding participant and algorithm characteristics
      and assessed each study's methodological rigor using a pre-defined approach.
      RESULTS: Ten publications addressing stillbirth and four addressing spontaneous
      abortion met our inclusion criteria. The International Classification of
      Diseases, Ninth Revision (ICD-9) codes most commonly used in algorithms for
      stillbirth were those for intrauterine death (656.4) and stillborn outcomes of
      delivery (V27.1, V27.3-V27.4, and V27.6-V27.7). Papers identifying spontaneous
      abortion used codes for missed abortion and spontaneous abortion: 632, 634.x, as
      well as V27.0-V27.7. Only two studies identifying stillbirth reported validation
      of algorithms. The overall positive predictive value of the algorithms was high
      (99%-100%), and one study reported an algorithm with 86% sensitivity. However,
      the predictive value of individual codes was not assessed and study populations
      were limited to specific geographic areas. CONCLUSIONS: Additional validation
      studies with a nationally representative sample are needed to confirm the optimal
      algorithm to identify stillbirths or spontaneous abortion in administrative and
      claims databases.'

PMID- 24331079
TI  - A systematic review of validated methods for identifying uveitis using
      administrative or claims data.
AB  - PURPOSE: To review algorithms used to identify uveitis in administrative and
      claims databases. METHODS: We searched the MEDLINE database via PubMed from 1991
      to September 2012 using vocabulary and key terms related to uveitis. We also
      searched the reference lists of included studies. Two investigators independently
      assessed studies against pre-determined inclusion criteria. The same two
      investigators independently extracted data regarding participant and algorithm
      characteristics and assessed a study's methodological rigor using a pre-defined
      approach. RESULTS: Seven studies met inclusion criteria. Variability exists among
      algorithms employed in these studies for finding cases of uveitis and related
      conditions as well as in use and implementation of validation methods. Of the
      seven included studies, three involved case validation. One used a narrow
      algorithm in addition to text mining of electronic medical records to identify
      incident cases and found a positive predictive value of 52.1%. The other two,
      which used broader uveitis definitions and included both incident and prevalent
      cases, found positive predictive values of 24.8% and 52.6%. CONCLUSIONS: Further
      research, with case as well as individual code validation, is needed to determine
      appropriate uveitis algorithms for purposes of active surveillance in
      administrative data. Decisions about which algorithm to use will depend on the
      desired balance of sensitivity and specificity.

PMID- 24331078
TI  - A systematic review of validated methods for identifying transverse myelitis
      using administrative or claims data.
AB  - PURPOSE: To identify and assess billing, procedural, or diagnostic code
      algorithms used to identify transverse myelitis in administrative databases.
      METHODS: We searched the MEDLINE database from 1991 to September 2012 using
      controlled vocabulary and key terms related to transverse myelitis. We also
      searched the reference lists of included studies. Two investigators independently
      assessed the full text of studies against pre-determined inclusion criteria. Two
      reviewers independently extracted data regarding participant and algorithm
      characteristics. RESULTS: Three studies met criteria for inclusion in this
      review. The only algorithm based solely on administrative claims data with a
      reported positive predictive value included five ICD-9 codes (codes 341.20,
      341.21, 341.22, 323.8, 323.9). The positive predictive value for physician
      diagnosed acute transverse myelitis was 62%. CONCLUSIONS: More research is needed
      to establish an accurate algorithm to identify transverse myelitis in large
      administrative databases using diagnosis and/or procedure codes. Use of
      standardized consensus definitions, clear description for algorithm selection,
      and reporting of validation procedure and results would be most beneficial.

PMID- 24331080
TI  - Post-licensure rapid immunization safety monitoring program (PRISM) data
      characterization.
AB  - BACKGROUND: The Post-Licensure Rapid Immunization Safety Monitoring (PRISM)
      program is the immunization safety monitoring component of FDA's Mini-Sentinel
      project, a program to actively monitor the safety of medical products using
      electronic health information. FDA sought to assess the surveillance capabilities
      of this large claims-based distributed database for vaccine safety surveillance
      by characterizing the underlying data. METHODS: We characterized data available
      on vaccine exposures in PRISM, estimated how much additional data was gained by
      matching with select state and local immunization registries, and compared
      vaccination coverage estimates based on PRISM data with other available data
      sources. We generated rates of computerized codes representing potential health
      outcomes relevant to vaccine safety monitoring. Standardized algorithms including
      ICD-9 codes, number of codes required, exclusion criteria and location of the
      encounter were used to obtain the background rates. RESULTS: The majority of the
      vaccines routinely administered to infants, children, adolescents and adults were
      well captured by claims data. Immunization registry data in up to seven states
      comprised between 5% and 9% of data for all vaccine categories with the exception
      of 10% for hepatitis B and 3% and 4% for rotavirus and zoster respectively.
      Vaccination coverage estimates based on PRISM's computerized data were similar to
      but lower than coverage estimates from the National Immunization Survey and
      Healthcare Effectiveness Data and Information Set. For the 25 health outcomes of
      interest studied, the rates of potential outcomes based on ICD-9 codes were
      generally higher than rates described in the literature, which are typically
      clinically confirmed cases. CONCLUSION: PRISM program's data on vaccine exposures
      and health outcomes appear complete enough to support robust safety monitoring.

PMID- 24331081
TI  - Seasonality of reported tuberculosis cases from 2006 to 2010 in Wuhan, China.
AB  - We investigated the seasonality of tuberculosis (TB) in Wuhan, China, to evaluate
      the increased risk of disease transmission during each season and to develop an
      effective TB control strategy. We applied spectral analysis to the weekly
      prevalence data of sputum smear positive (SSP) and sputum smear negative (SSN)
      pulmonary TB reported from 2006 to 2010. Cases of both SSP and SSN feature 1.0-
      and 0.5-year periodic modes. The least squares method was used to fit curves to
      the two periodic modes for SSP and SSN data. The curves demonstrated dominant
      peaks in spring similar to cases reported previously for other locations. Notably
      for SSP, dominant peaks were also observed in summer. The spring peaks of SSP and
      SSN were explained in terms of poorly ventilated and humid rooms and vitamin D
      deficiency. For the summer peaks of SSP, summer influenza epidemics in Wuhan may
      contribute to the increase in TB prevalence.

PMID- 24331082
TI  - On the relation among mood, apathy, and anosognosia in Alzheimer's disease.
AB  - This review explores the relationships between depression, apathy, and
      anosognosia in Alzheimer's disease. Depressed mood is found to be associated with
      less anosognosia, while greater apathy is associated with more anosognosia, and
      the contrasting reasons for these associations are discussed. The review also
      describes recent research findings indicating a dissociation between impaired
      awareness of condition/deficit and preserved emotional reactivity in response to
      illness-related material or the experience of failure in tests. We conclude by
      pointing to future directions for this area of research and clinical
      implications.

PMID- 24331083
TI  - A reassessment of the presumed Neandertal remains from San Bernardino Cave,
      Italy.
AB  - In 1986-1987, three human remains were unearthed from macro-unit II of San
      Bernardino Cave (Berici Hills, Veneto, Italy), a deposit containing a late
      Mousterian lithic assemblage. The human remains (a distal phalanx, a lower right
      third molar and a lower right second deciduous incisor) do not show diagnostic
      morphological features that could be used to determine whether they were from
      Homo neanderthalensis or Homo sapiens. Despite being of small size, and thus more
      similar to recent H. sapiens, the specimens were attributed to Neandertals,
      primarily because they were found in Mousterian layers. We carried out a
      taxonomic reassessment of the lower right third molar (LRM3; San Bernardino 4)
      using digital morphometric analysis of the root, ancient DNA analysis, carbon and
      nitrogen isotope analyses, and direct accelerator mass spectrometry (AMS)
      radiocarbon dating of dentine collagen. Mitochondrial DNA analysis and root
      morphology show that the molar belongs to a modern human and not to a Neandertal.
      Carbon 14 ((14)C) dating of the molar attributes it to the end of the Middle Ages
      (1420-1480 cal AD, 2 sigma). Carbon and nitrogen isotope analyses suggest that
      the individual in question had a diet similar to that of Medieval Italians. These
      results show that the molar, as well as the other two human remains, belong to
      recent H. sapiens and were introduced in the Mousterian levels post
      depositionally. 

PMID- 24331086
TI  - Targeted lymph node assessment in gastrointestinal neoplasms.

PMID- 24331087
TI  - Absorption and metabolism of formaldehyde in solutions by detached banana leaves.
AB  - Detached banana leaves are one of the by-products of banana production. In this
      study, the absorption and metabolism of formaldehyde (HCHO) in solutions by
      detached banana leaves was investigated under submergence conditions. The results
      showed that banana leaves could effectively absorb HCHO in the treatment
      solutions, and the relationship between HCHO absorption and treatment time
      appeared to fit a radical root function model. (13)C nuclear magnetic resonance
      analysis was used to investigate the ability of detached banana leaves to
      metabolise H(13)CHO, and the results indicated that the H(13)CHO absorbed from
      the treatment solutions was converted into non-toxic compounds. High amounts of
      [U-(13)C]glucose, [U-(13)C]fructose, [3-(13)C]serine and [3-(13)C]citrate were
      produced as a result of H(13)CHO metabolism in banana leaves, and the production
      of a small amount of [2,4-(13)C]citrate and [2,3-(13)C]alanine was also observed.
      These results suggest that detached banana leaves can metabolise H(13)CHO and
      convert it to non-toxic compounds. The metabolic pathways that produce these
      intermediates in detached banana leaves are postulated based on our (13)C nuclear
      magnetic resonance data.

PMID- 24331088
TI  - Seminars in Pediatric Surgery. Neonatal physiology. Preface.

PMID- 24331089
TI  - Brain vascular and hydrodynamic physiology.
AB  - Protecting the brain in vulnerable infants undergoing surgery is a central aspect
      of perioperative care. Understanding the link between blood flow, oxygen
      delivery, and oxygen consumption leads to a more informed approach to bedside
      care. In some cases, we need to consider how high we can let the partial pressure
      of carbon dioxide go before we have concerns about risk of increased cerebral
      blood volume and change in intracranial hydrodynamics. Alternatively, in almost
      all such cases, we have to address the question of how low can we let the blood
      pressure drop before we should be concerned about brain perfusion. This review
      provides a basic understanding of brain bioenergetics, hemodynamics,
      hydrodynamics, autoregulation, and vascular homeostasis to changes in blood
      gases, which is fundamental to our thinking about bedside care and monitoring. 

PMID- 24331090
TI  - Neonatal cardiovascular physiology.
AB  - The pediatric surgeon deals with a large number and variety of congenital defects
      in neonates that frequently involve early surgical intervention and care. Because
      the neonatal cardiac physiology is unique, starting with the transition from
      fetal circulation and including differences in calcium metabolism and myocardial
      microscopic structure and function, it serves the pediatric surgeon well to have
      a sound understanding of these principles and how they directly and indirectly
      affect their plans and treatments. In addition, many patients will have
      associated congenital heart disease that can also dramatically influence not only
      the surgical and anesthetic care but also the timing and planning of procedures.
      Finally, the pediatric surgeon is often called upon to treat conditions and
      complications associated with complex congenital heart disease such as feeding
      difficulties, bowel perforations, and malrotation in heterotaxy syndromes. In
      this article, we will review several unique aspects of neonatal cardiac
      physiology along with the basic physiology of the major groups of congenital
      heart disease to better prepare the training and practicing pediatric surgeon for
      care of these complex and often fragile patients. 

PMID- 24331091
TI  - Neonatal pulmonary physiology.
AB  - Managing pulmonary issues faced by both term and preterm infants remains a
      challenge to the practicing pediatric surgeon. An understanding of normal fetal
      and neonatal pulmonary development and physiology is the cornerstone for
      understanding the pathophysiology and treatment of many congenital and acquired
      problems in the neonate. Progression through the phases of lung development and
      the transition to postnatal life requires a symphony of complex and overlapping
      events to work in concert for smooth and successful transition to occur.
      Pulmonary physiology and oxygen transport in the neonate are similar to older
      children; however, there are critical differences that are important to take into
      consideration when treating the youngest of patients. Our understanding of fetal
      and neonatal pulmonary physiology continues to evolve as the molecular and
      cellular events governing these processes are better understood. This deeper
      understanding has helped to facilitate groundbreaking research, leading to
      improved technology and treatment of term and preterm infants. As therapeutics
      and research continue to advance, a review of neonatal pulmonary physiology is
      essential to assist the clinician with his/her management of the wide variety of
      challenging congenital and acquired pulmonary disease. 

PMID- 24331092
TI  - Neonatal liver physiology.
AB  - In the neonate, the liver is relatively immature and undergoes several changes in
      its functional capacity during the early postnatal period. The essential liver
      functions can be classified into three categories: metabolism, detoxification,
      and bile synthesis. In general, the immature liver function has limited
      consequences on the healthy term neonate. However, preterm neonates are
      particularly susceptible to the effects of the immature liver function placing
      them at risk of hypoglycemia, hyperbilirubinemia, cholestasis, bleeding, and
      impaired drug metabolism. An appreciation of the dynamic changes in liver
      function during the neonatal period is essential for successful management of
      neonates who require medical and surgical interventions. This review will focus
      on the neonatal liver function as well as the changes that the liver undergoes as
      it matures. 

PMID- 24331093
TI  - Neonatal intestinal physiology and failure.
AB  - The neonatal intestine is a complex organ that regulates the absorption of
      nutrients essential for growth and development. Intestinal failure results from
      insufficient or functionally inadequate bowel and can lead to failure of neonatal
      growth and development. Current literature on neonatal intestinal physiology and
      failure was reviewed and summarized. A homeostatic interplay of electrolytes,
      enzymes, and hormonal regulators is essential to achieve the physiologic balance
      needed for adequate intestinal performance. Physiologic consequences of
      intestinal failure are dependent on the length and anatomic location of the
      diseased or surgically resected bowel. Intestinal failure leads to disruption of
      normal intestinal physiology and may have long-term consequences for growth and
      development if inadequately treated. Parenteral nutrition remains the mainstay of
      treatment for neonatal intestinal failure. 

PMID- 24331094
TI  - Neonatal renal physiology.
AB  - The renal system plays a tremendous role in growth and development of infants and
      children. The kidney itself also undergoes a maturation process as it transitions
      from the fetal to the extrauterine environment. Renal function continues to
      undergo further adaptive changes in the neonatal period. It is important for the
      clinician caring for neonates to be aware of the expected fluid shifts,
      electrolyte handling, and renal functional capacity as these "normal" changes
      will become quite relevant when medical or surgical pathology is present. The
      preterm neonates are especially vulnerable due to their functionally immature
      kidneys. Renal function in the preterm neonate is not only immature at birth but
      there is a significant delay in the renal function to achieve its full capacity.
      This review highlights the physiologic adaptations of the kidney and its effects
      on the body during the neonatal period. 

PMID- 24331095
TI  - Neonatal hematology.
AB  - Neonatal hematology is a complex and dynamic process in the pediatric population.
      Surgeons frequently encounter hematologic issues regarding hemostasis,
      inflammation, and wound healing. This publication provides a surgeon-directed
      review of hematopoiesis in the newborn, as well as an overview of the current
      understanding of their hemostatic profile under normal and pathologic conditions.

PMID- 24331096
TI  - Endocrine physiology in the newborn.
AB  - Evaluation of suspected endocrine pathology in newborn infants requires knowledge
      of the dynamic changes that characterize normal hormonal function in the neonatal
      period. This article reviews normal endocrine physiology as it pertains to common
      clinical scenarios encountered in neonatal surgical patients. Topics covered
      include thyroid and adrenal function as well as glucose and calcium metabolism. 

PMID- 24331097
TI  - Seminars in Pediatric Surgery increasing to six issues per year.

PMID- 24331098
TI  - Investigating the predictive ability of gait speed and quadriceps strength for
      incident falls in community-dwelling older women at high risk of fracture.
AB  - Gait speed is a recommended geriatric assessment of physical performance, but may
      not be regularly examined in clinical settings. We aimed to investigate whether
      quadriceps strength tests demonstrate similar predictive ability for incident
      falls as gait speed in older women. We investigated 135 female volunteers aged
      mean+/-SD 76.7+/-5.0 years (range 70-92) at high risk of fracture. Participants
      completed gait speed assessments using the GAITRite Electronic Walkway System,
      and quadriceps strength assessments using a hand-held dynamometer (HHD).
      Participants reported incident falls monthly for 3.7+/-1.2 years. N=99 (73%)
      participants fell 355 times during the follow-up period (mean fall rate 83 per
      100 person years). We observed a reduced odds ratio for multiple falls (0.83, 95%
      CI 0.70-0.98) and a reduced hazard ratio for time to first fall (0.90, 95% CI
      0.83-0.98), according to quadriceps strength. There was also a significantly
      shorter time to first fall for those with low quadriceps strength (<7.0 kg;
      lowest tertile) compared with those with normal quadriceps strength (estimated
      means [95% CI] 1.54 [1.02, 2.06] vs. 2.23 [1.82, 2.64] years; P=0.019), but not
      for those with low (<1.0 m/s) vs. normal gait speed (P=0.15). Quadriceps strength
      is a significant predictor of incident falls over three years amongst community
      dwelling older women at high risk of fracture. Quadriceps strength tests may be
      an acceptable alternative to gait speed for geriatric assessments of falls risk.

PMID- 24331099
TI  - Bariatric surgery as a treatment for type 2 diabetes.

PMID- 24331100
TI  - Bariatric surgery: An IDF statement for obese Type 2 diabetes.

PMID- 24331101
TI  - Aloe vera phytosterols act as ligands for PPAR and improve the expression levels
      of PPAR target genes in the livers of mice with diet-induced obesity.
AB  - SUMMARY: Lophenol (Lo) and cycloartanol (Cy), minor phytosterols of Aloe vera
      gel, were previously identified as anti-diabetic compounds, and these compounds
      also reduced body fat in a type 2 diabetic model animal. In this study, we
      investigated the effects of Lo and Cy on peroxisome proliferator activated
      receptors (PPAR) using a luciferase reporter assay. DNA microarray and real-time
      quantitative RT-PCR (qPCR) analyses were also performed in a diet-induced obesity
      (DIO) mouse model. The Aloe phytosterols activated PPAR in a dose-dependent
      manner. The expression levels of many PPAR target genes were changed in the Aloe
      phytosterol group compared with those in the control high-fat diet (HFD) group.
      In particular, the expression levels of Fatp1, Acox1, Cpt1, and Hmgcs2 were
      significantly increased in the Aloe phytosterol group compared with those in the
      control HFD group; however, the expression level of ApoCIII was significantly
      decreased in the Aloe phytosterol group. We confirmed that Aloe phytosterols
      activate PPAR transcription in vitro. In addition, quantitative gene expression
      analysis in DIO mice suggested that Aloe phytosterols improve fatty acid
      metabolism in the liver.:

PMID- 24331102
TI  - Change in waist circumference and the progression of subclinical atherosclerosis
      in type 2 diabetes patients.
AB  - SUMMARY:  OBJECTIVE: We aimed to assess the effect of reducing body weight, waist
      circumference, and various metabolic parameters on the progression of carotid
      intima media thickness (IMT) in Korean type 2 diabetes patients. METHODS: This
      study comprised of 173 patients. Anthropometric measurements, metabolic
      parameters, and carotid IMT were measured at baseline and 1 year later. RESULTS:
      There were significant differences in waist circumference, HbA1c, and mean left
      and right IMT after 1 year. The change in waist circumference correlated with
      changes in HbA1c and changes in right and left IMT after adjusting for age, sex,
      and medications that could influence the IMT. In multiple regression analysis,
      the change in waist circumference was a significant predictor of the progression
      of maximum right and left IMT, with a marginal significance for the latter, and
      mean left IMT, independent of changes in body weight, BMI, HbA1c level, and the
      use of anti-hyperlipidemic, antiplatelet agents and thiazolidinediones.
      CONCLUSION: Controlling abdominal obesity seems to have a significant impact on
      the progression of subclinical atherosclerosis in patients with diabetes, and
      therefore, more efforts should be made toward reducing waist circumference to
      inhibit overt atherosclerotic diseases.

PMID- 24331103
TI  - Norm references of fat-free mass index and fat mass index and subtypes of obesity
      based on the combined FFMI-%BF indices in the Korean adults aged 18-89 yr.
AB  - SUMMARY:  OBJECTIVE: To establish reference values for fat-free mass index
      (FFMI), fat mass index (FMI), and percent body fat (%BF) in a large Korean adult
      group of apparently healthy subjects, and to analyze the characteristics of body
      composition indices among the subtypes of obesity in Korean adults. SUBJECTS AND
      METHODS: A multicenter, cross-sectional study was conducted on a sample of 1275
      community-dwelling healthy Koreans, 504 men and 771 women, aged 18-89 years. Body
      composition parameters were measured by dual-energy X-ray absorptiometry. FFMI
      (FFM/height squared) and FMI (FM/height squared) were calculated, and then three
      subtypes of obesity were divided by FFMI; underlean (or sarcopenic),
      proportional, and heavy (or muscular) obesity. RESULTS: The reference values (5th
      95th percentile) of the reference group (18-59 yr) for the FFMI was 16.3-22.3
      kg/m(2) in men and 13.3-17.8 kg/m(2) in women. The %BF increased with age because
      of the reduction of FFM. Due to lower FFMI in the oldest men, they had the lowest
      BMI while FMI and BMI of Korean women increased with age like Caucasian women.
      The %BF among three subtypes of obesity was similar while FMI and BMI were
      increased as FFMI increased. The prevalence of underlean obesity in men was more
      than double in women. CONCLUSION: It is essential to analyze FFMI as well as %BF
      because %BF alone cannot explain the effects of ageing on FFM and the
      characteristics of subtypes of obesity. This is the first study to present DXA
      determined age- and sex-specific percentiles for body composition indices in
      Korean adults. These reference values may be useful for clinical evaluation of
      body composition and nutritional status for Korean adults.

PMID- 24331104
TI  - Acute effect of late evening meal on diurnal variation of blood glucose and
      energy metabolism.
AB  - SUMMARY:  OBJECTIVE: The notion that late evening meal promotes weight gain is
      popular, and it may also elicit postprandial hyperglycemia, since glucose
      tolerance decreases during midnight. Diabetic patients with night-eating
      symptoms, compared with patients without night-eating behaviors, are more likely
      to be obese and to have elevated A1c. However, epidemiological analysis adjusted
      for difference in total energy intake did not identify nighttime eating as the
      risk of obesity. The present study evaluated the effect of a single loading of
      late evening meal on diurnal variation of blood glucose and 24-h energy
      expenditure. METHODS: Ten young adults stayed twice in a room-size respiratory
      chamber for 24 h, in a randomized repeated-measures design. After the entrance to
      the chamber at 1700 h, the subjects took normal (1900 h) or late (2230 h) evening
      meal, breakfast and lunch, and remained in the chamber until 1700 h. Time course
      of blood glucose was measured by continuous glucose monitoring system. RESULTS:
      Late evening meal enhanced postprandial blood glucose response to the evening
      meal and the subsequent breakfast. Overall 24 h average blood glucose level was
      also elevated by late evening meal. Late evening meal shifted postprandial
      increase in energy expenditure toward late at night, but overall 24 h energy
      expenditure remained almost identical in the two dietary conditions. CONCLUSIONS:
      The present study under controlled sedentary condition supports the notion that a
      single loading of late evening meal enhances average blood glucose over 24 h, but
      does not support that late evening meal reduces 24 h energy expenditure.

PMID- 24331105
TI  - Treatment of obesity in children: Parent's perceived emotional barriers as
      predictor of change in body fat.
AB  - SUMMARY:  AIM: Research supports the use of family-based interventions in the
      treatment of obesity in children, but there is a lack of knowledge about what
      factors affect parents' ability to carry out the lifestyle changes necessary to
      reduce their child's obesity. The aim of the present study was to examine whether
      parents' self-efficacy, perceived emotional barriers, subjective norms, and
      attitudes could predict change in their children's body fat at 6 month and 2 year
      follow-ups after a family-based treatment of obesity. METHODS: Body Mass Index
      Standard Deviation Scores (BMI SDS) were calculated and body fat (dual-energy X
      ray absorptiometry) were measured in 99 treatment-seeking children with obesity
      (ages 7-12; 48 girls, 51 boys; mean BMI SDS = 2.99) at baseline, after 6 month
      and after 2 year follow-up. Parental cognitions regarding diet and physical
      activity were examined by parent-completed questionnaires. Structural equation
      modeling (SEM) was used to test whether the selected health cognitions could
      predict treatment outcome. RESULTS: Parental perceived emotional barriers was a
      significant predictor of change in body fat at 6 month (beta = -.32, p = .001)
      and 2 year (beta = -.38, p = .002) follow-up when the initial body fat values
      were controlled. Self-efficacy, subjective norms and attitudes did not improve
      the amount of variance explained. CONCLUSION: Parents' perceived emotional
      barriers significantly predict change in total body fat in children treated for
      obesity. In order to increase treatment-efficacy, perceived emotional barriers
      should be addressed.

PMID- 24331106
TI  - Engaging men in weight loss: Experiences of men who participated in the male only
      SHED-IT pilot study.
AB  - SUMMARY: Recruiting men to weight loss programs is notoriously difficult and
      little is known about the experiences of men who participate in weight loss
      programs. The aims of this paper were to report the perceptions and experiences
      of men who enrolled in the SHED-IT (Self-Help, Exercise, Diet and Information
      Technology) randomized controlled trial in the context of (1) what attracted them
      to the program, (2) their satisfaction with the program and its components, and
      (3) their suggestions for improvements to the program. The SHED-IT program
      exclusively targeted men and was developed to appeal to men. Individual semi
      structured interviews were conducted with 18 overweight/obese (BMI between 25 and
      37 kg/m(2)) men aged 18-60 years who were employed or enrolled at the University
      of Newcastle and who had been enrolled to the SHED-IT trial and randomly
      allocated to receive either the Internet intervention or basic weight-loss
      Information Only. Significant weight loss was achieved by both groups. A thematic
      analysis was undertaken applying the constant comparison method. Results
      indicated that lack of knowledge was a major weight loss barrier and men were
      attracted to a program that did not require extensive time commitments, was
      tailored for men and allowed inclusion of 'treat' food and drinks. Men were
      satisfied with both programs and valued the education about energy balance and
      the humour used to deliver simple messages. More face-to-face contact was a
      common suggestion for improvement. Our findings will inform future weight loss
      interventions for men and assist researchers and practitioners to engage men in
      weight loss.:

PMID- 24331107
TI  - A 12-week aerobic exercise program without energy restriction improves
      intrahepatic fat, liver function and atherosclerosis-related factors.
AB  - SUMMARY:  OBJECTIVE: To study the effects of a 12-week continuous aerobic
      exercise program without energy restriction on intrahepatic fat, indices of liver
      function (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and
      gamma-glutamyl transpeptidase [gammaGTP]), plasminogen activator inhibitor-1 (PAI
      1) and insulin resistance (HOMA-IR). METHODS: Subjects were divided into two
      groups based on the degree of intrahepatic fat accumulation at baseline (high
      liver fat [HLF]: n = 13; low liver fat [LLF]: n = 14). Participants were
      instructed to exercise for more than 300 min per week at the lactate threshold.
      Fat accumulation (intramuscular, intrahepatic, visceral and subcutaneous fat) was
      evaluated by computed tomography. Blood samples were taken to determine the
      levels of AST, ALT, PAI-1, glucose and insulin. RESULTS: Weight, body mass index,
      body fat, visceral fat and subcutaneous fat decreased significantly in both
      groups between baseline and post-intervention (P < 0.05), but were not
      significantly different between the two groups (P > 0.05). Intrahepatic fat, AST,
      ALT and PAI-1 improved significantly between baseline and post-intervention in
      the HLF group (P < 0.05; AST, P = 0.052), and improvements were significantly
      greater than those in the LLF group (P < 0.05). gammaGTP decreased significantly
      in the HLF group between baseline and post-intervention (P < 0.05), but was not
      significantly different between the two groups (P > 0.05). HOMA-IR did not
      significantly improve between baseline and post-intervention either within or
      between the two groups (P > 0.05). CONCLUSION: This study revealed that a 12-week
      continuous aerobic exercise program without energy restriction might improve
      intrahepatic fat, liver function and atherosclerosis-related factors.

PMID- 24331108
TI  - Patient behaviors associated with weight regain after laparoscopic gastric
      bypass.
AB  - SUMMARY:  BACKGROUND: Patients undergoing gastric bypass lose substantial weight,
      but 20% regain weight starting at 2 years after surgery. Our objective was to
      identify behavioral predictors of weight regain after laparoscopic Roux-en-Y
      gastric bypass (LRYGB). METHODS: We retrospectively surveyed 197 patients for
      factors predictive of weight regain (>=15% from lowest weight to weight at survey
      completion). Consecutive patients who had bariatric surgery from 1/2003 through
      12/2008 were identified from an existing database. Response rate was 76%, with
      150 patients completing the survey. RESULTS: Follow-up after LRYGB was 45.0 +/-
      12.7 months, 22% of patients had weight regain. After controlling for age,
      gender, and follow-up time, factors associated with weight regain included low
      physical activity (odds ratio (OR) 6.92, P = 0.010), low self-esteem (OR 6.86, P
      = 0.008), and Eating Inventory Disinhibition (OR 1.30, P = 0.029). CONCLUSIONS:
      Physical activity, self-esteem, and maladaptive eating may be associated with
      weight regain after LRYGB. These factors should be addressed in prospective
      studies of weight loss following bariatric surgery, as they may identify patients
      at risk for weight regain who may benefit from tailored interventions.

PMID- 24331109
TI  - Inhibition of the Mycobacterium tuberculosis reserpine-sensitive efflux pump
      augments intracellular concentrations of ciprofloxacin and enhances
      susceptibility of some clinical isolates.
AB  - BACKGROUND/PURPOSE: Active efflux is known to play a major role in the resistance
      of many bacteria to antibiotics. To evaluate the possibility of overcoming
      resistance by suppressing the efflux, we determined the effect of reserpine, an
      efflux pump inhibitor. METHODS: Intracellular accumulations and the minimal
      inhibitory concentrations (MICs) of ciprofloxacin in M. tuberculosis H37Rv and 16
      clinical isolates were determined, compared, and analyzed. Nine of the clinical
      isolates were resistant to isoniazid and rifampin (multiple-drug resistant MDR).
      Five of these were resistant to ciprofloxacin. RESULTS: A reserpine-inhibited
      efflux system was identified in the H37Rv control and 10:1 (90.9%) of
      ciprofloxacin-susceptible and 4:1 (80%) of ciprofloxacin-resistant clinical
      isolates. The MIC of ciprofloxacin decreased in the presence of reserpine in 3/10
      (30%) of the ciprofloxacin-susceptible and 2/4 (50%) of the MDR ciprofloxacin
      resistant strains that expressed efflux pumps. Two of the efflux-positive,
      ciprofloxacin-resistant strains in which the MIC of ciprofloxacin was not
      decreased by reserpine were found to carry a D94A gyrA mutation. In contrast, two
      strains with the D94G gyrA mutation were susceptible to ciprofloxacin in the
      presence of reserpine. An efflux-negative strain, highly resistant to multiple
      antibiotics, was found to have a novel G247S mutation that differs from known
      mutations in the QRDR region of the gyrA gene. CONCLUSION: These findings
      indicate t hat reserpine can increase intracellular concentrations of
      ciprofloxacin, but is unable to overcome other mechanisms of resistance in
      clinical isolates.

PMID- 24331110
TI  - Orthodontic treatment for a mandibular prognathic girl of short stature under
      growth hormone therapy.
AB  - This report presents a case of a 12-year-old girl with maxillary deficiency,
      mandibular prognathism, and facial asymmetry, undergoing growth hormone (GH)
      therapy due to idiopathic short stature. Children of short stature with or
      without GH deficiency have a deviating craniofacial morphology with overall
      smaller dimensions; facial retrognathism, especially mandibular retrognathism;
      and increased facial convexity. However, a complete opposite craniofacial pattern
      was presented in our case of a skeletal Class III girl with idiopathic short
      stature. The orthodontic treatment goal was to inhibit or change the direction of
      mandibular growth and stimulate the maxillary growth of the girl during a course
      of GH therapy. Maxillary protraction and mandibular retraction were achieved
      using occipitomental anchorage (OMA) orthopedic appliance in the first stage of
      treatment. In the second stage, the patient was treated with a fixed orthodontic
      appliance using a modified multiple-loop edgewise archwire technique of
      asymmetric mechanics and an active retainer of vertical chin-cup. The treatment
      led to an acceptable facial profile and obvious facial asymmetry improvement.
      Class I dental occlusion and coincident dental midline were also achieved. A 31/2
      year follow-up of the girl at age 18 showed a stable result of the orthodontic
      and dentofacial orthopedic treatment. Our case shows that the OMA orthopedic
      appliance of maxillary protraction combined with mandibular retraction is
      effective for correcting skeletal Class III malocclusion with midface deficiency
      and mandibular prognathism in growing children with idiopathic short stature
      undergoing GH therapy.

PMID- 24331111
TI  - Pneumococcal conjugate vaccines (PCV). Foreword.

PMID- 24331113
TI  - How can we achieve consensual indicators to be better accepted and more widely
      used?

PMID- 24331112
TI  - Standard method for detecting upper respiratory carriage of Streptococcus
      pneumoniae: updated recommendations from the World Health Organization
      Pneumococcal Carriage Working Group.
AB  - In 2003 the World Health Organization (WHO) convened a working group and
      published a set of standard methods for studies measuring nasopharyngeal carriage
      of Streptococcus pneumoniae (the pneumococcus). The working group recently
      reconvened under the auspices of the WHO and updated the consensus standard
      methods. These methods describe the collection, transport and storage of
      nasopharyngeal samples, as well as provide recommendations for the identification
      and serotyping of pneumococci using culture and non-culture based approaches. We
      outline the consensus position of the working group, the evidence supporting this
      position, areas worthy of future research, and the epidemiological role of
      carriage studies. Adherence to these methods will reduce variability in the
      conduct of pneumococcal carriage studies undertaken in the context of
      pneumococcal vaccine trials, implementation studies, and epidemiology studies
      more generally so variability in methodology does not confound the interpretation
      of study findings. 

PMID- 24331114
TI  - Viscoelastic properties measurement of the prolapsed anterior vaginal wall: a
      patient-directed methodology.
AB  - OBJECTIVE: In-vivo measurement of the viscoelastic properties of the prolapsed
      anterior vaginal wall (AVW) in post-menopausal women undergoing cystocele repair.
      STUDY DESIGN: A BTC-2000 cutometer-like instrument was introduced during vaginal
      repair of symptomatic stage 2-3 AVW prolapse. Under anesthesia, 10-mm orifice
      probe was applied to the AVW at the level of the bladder neck. A suction pressure
      ramp (0 to -147 mmHg in 6s) was delivered causing tissue uplift, followed by
      immediate release to 0 mmHg, measuring tissue relaxation for 20s. Similar
      measurements were performed over the suprapubic region (SP) for comparison
      purpose. The rate of tissue recovery was obtained by fitting a Voigt model to the
      data and expressing results as the ratio E/eta [(spring modulus E)/(dashpot
      viscosity eta)]. The effective strain energy (SE) was calculated from the
      pressure-uplift data and evaluated from initiation to: (1) maximum storage in
      tissue at peak vacuum; (2) tissue recovery after vacuum release; (3) net SE loss
      over the entire loading-unloading cycle. RESULTS: In 22 women, higher AVW peak
      and residual tissue uplift values, and lower E/eta ratios were found compared
      with SP results. The AVW stored less elastic strain energy at peak vacuum than
      did the SP, and AVW net energy loss over the uplift-recovery cycle was greater
      than for SP controls. Not only was the AVW more compliant than the SP, with
      higher viscous damping, but the tissue was also less able to store recoverable
      energy upon distension. CONCLUSION: Such in-vivo measurements quantify the
      biomechanical properties of the prolapsed AVW and may assist in its management.

PMID- 24331115
TI  - Does dehydroepiandrosterone supplementation really affect IVF-ICSI outcome in
      women with poor ovarian reserve?
AB  - OBJECTIVES: It is difficult to choose the correct fertility treatment in women
      with poor ovarian reserve. Although various methods have been used, the
      management of controlled ovarian hyperstimulation is not easy in poor responders.
      The aim of this study was to evaluate the efficacy of dehydroepiandrosterone
      (DHEA) on in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI)
      outcome of poor responders. STUDY DESIGN: This was a randomized, prospective
      controlled trial. Women with serum antimullerian hormone<1 ng/ml or serum
      follicle-stimulating hormone>15 IU/l and antral follicle count <4 on day 2 of the
      menstrual cycle were considered to have poor ovarian reserve. All women were
      treated with a microdose induction protocol. Women in the study group received
      IVF-ICSI and DHEA 75 mg daily for 12 weeks. Women in the control group received
      IVF-ICSI without DHEA supplementation. RESULTS: In total, 208 women with
      diminished ovarian reserve was enrolled in the study, 104 in the study group and
      104 in the control group. The number of oocytes retrieved and the fertilization
      rate were slightly higher in the study group, but the pregnancy rate was higher
      in the control group. The differences were not significant. CONCLUSIONS: The
      results failed to show that DHEA supplementation enhances IVF-ICSI outcome in
      women with poor ovarian reserve.

PMID- 24331116
TI  - Do injury characteristics predict the severity of acute neuropsychological
      deficits following sports-related concussion? A meta-analysis.
AB  - The utility of injury characteristics for predicting the severity of post
      concussion outcomes remains equivocal. The purpose of this meta-analysis was to
      quantify the predictive relationship between these variables to inform
      classification of acute injury severity. Thirty-one empirical samples of
      concussed athletes, for which rates of loss of consciousness and/or amnesia were
      reported, were included in a meta-analysis evaluating acute outcomes following
      sports-related concussion. Outcome measures of interest were neuropsychological
      tests first administered 1-10 days post-injury. Loss of consciousness and
      anterograde amnesia significantly predicted more severe neuropsychological
      deficits within 10 days of concussion in studies using pre-injury baseline, but
      not control group, comparisons. Retrograde amnesia significantly predicted acute
      neuropsychological dysfunction (d = -1.03) irrespective of comparison group.
      Although small sample sizes require conservative interpretation and future
      replication, the evidence suggests that retrograde amnesia, rather than loss of
      consciousness, may be used to classify the acute severity of concussion.

PMID- 24331117
TI  - Hemochromatosis and the heart--heavier than iron?

PMID- 24331118
TI  - Multi-level vascular aneurysms and polycystic kidney disease.

PMID- 24331119
TI  - Evaluation of the right ventricle: comparison of gated blood-pool single photon
      electron computed tomography and echocardiography with cardiac magnetic
      resonance.
AB  - BACKGROUND: The evaluation of the right ventricle (RV) is a challenge; as a
      result six transthoracic echocardiography (TTE) parameters have been suggested.
      While gated blood-pool single photon electron computed tomography (GBPS) is a
      promising technique, there is currently no completely automated and validated
      processing software available clinically. Consequently, cardiac magnetic
      resonance (CMR) imaging remains the gold standard for RV assessment. We aimed to
      compare RV evaluation by GBPS and TTE to CMR. METHODS: Fifty-eight patients
      underwent CMR, GBPS and TTE for RV assessment, including volumes, RVEF and TTE's
      indices of RV function (fractional area change (FAC), RV myocardial performance
      index by pulsed wave Doppler (MPI-PWD) and tissue Doppler (MPI-TDI) and tricuspid
      annular plane systolic excursion (TAPSE) by M-Mode and tissue Doppler (TAPSE
      TDI)). GBPS was performed using both a commercial (QBS) and the Montreal Heart
      Institute (MHI) proprietary software. RESULTS: Nuclear medicine derived volumes
      quantification showed very good correlations with CMR, for RV end-diastolic
      (r=0.84 and 0.77, all p<0.001) and end-systolic (r=0.82 and 0.67, all p<0.001)
      volumes by MHI and QBS software respectively. RVEF showed a significant
      correlation with CMR in patients with RVEF <= 45% (r=0.54, p=0.029 and r=0.55,
      p=0.028, by MHI and QBS respectively). Among TTE parameters, only FAC and MPI-TDI
      were significantly correlated with CMR-RVEF, mainly for RVEF <= 45% (r=0.63,
      p=0.011 and r=0.58, p=0.046). CONCLUSIONS: GBPS, both with MHI and QBS software,
      exhibited significant correlations with CMR for evaluation of the RV (volumes and
      decreased RVEF estimation). Among TTE's parameters, only FAC and MPI-TDI showed
      significant correlation with CMR with RVEF <= 45%.

PMID- 24331121
TI  - Increased vascularization during early healing after biologic augmentation in
      repair of chronic rotator cuff tears using autologous leukocyte- and platelet
      rich fibrin (L-PRF): a prospective randomized controlled pilot trial.
AB  - HYPOTHESIS: We hypothesized that arthroscopic rotator cuff repairs using
      leukocyte- and platelet-rich fibrin (L-PRF) in a standardized, modified protocol
      is technically feasible and results in a higher vascularization response and
      watertight healing rate during early healing. METHODS: Twenty patients with
      chronic rotator cuff tears were randomly assigned to 2 treatment groups. In the
      test group (N = 10), L-PRF was added in between the tendon and the bone during
      arthroscopic rotator cuff repair. The second group served as control (N = 10).
      They received the same arthroscopic treatment without the use of L-PRF. We used a
      double-row tension band technique. Clinical examinations including subjective
      shoulder value, visual analog scale, Constant, and Simple Shoulder Test scores
      and measurement of the vascularization with power Doppler ultrasonography were
      made at 6 and 12 weeks. RESULTS: There have been no postoperative complications.
      At 6 and 12 weeks, there was no significant difference in the clinical scores
      between the test and the control groups. The mean vascularization index of the
      surgical tendon-to-bone insertions was always significantly higher in the L-PRF
      group than in the contralateral healthy shoulders at 6 and 12 weeks (P = .0001).
      Whereas the L-PRF group showed a higher vascularization compared with the control
      group at 6 weeks (P = .001), there was no difference after 12 weeks of follow-up
      (P = .889). Watertight healing was obtained in 89% of the repaired cuffs.
      DISCUSSION/CONCLUSIONS: Arthroscopic rotator cuff repair with the application of
      L-PRF is technically feasible and yields higher early vascularization. Increased
      vascularization may potentially predispose to an increased and earlier cellular
      response and an increased healing rate.

PMID- 24331120
TI  - The obesity paradox in men with coronary heart disease and heart failure: the
      role of muscle mass and leptin.
AB  - AIMS: We have investigated the role of muscle mass, natriuretic peptides and
      adipokines in explaining the obesity paradox. BACKGROUND: The obesity paradox
      relates to the association between obesity and increased survival in patients
      with coronary heart disease (CHD) or heart failure (HF). METHODS: Prospective
      study of 4046 men aged 60-79 years followed up for a mean period of 11 years,
      during which 1340 deaths occurred. The men were divided according to the presence
      of doctor diagnosed CHD and HF: (i) no CHD or HF ii), with CHD (no HF) and (iii)
      with HF. RESULTS: Overweight (BMI 25-9.9 kg/m(2)) and obesity (BMI >= 30 kg/m(2))
      were associated with lower mortality risk compared to men with normal weight (BMI
      18.5-24.9 kg/m(2)) in those with CHD [hazards ratio (HR) 0.71 (0.56,0.91) and
      0.77 (0.57,1.04); p=0.04 for trend] and in those with HF [HR 0.57 (0.28,1.16) and
      0.41 (0.16,1.09; p=0.04 for trend). Adjustment for muscle mass and NT-proBNP
      attenuated the inverse association in those with CHD (no HF) [HR 0.78 (0.61,1.01)
      and 0.96 (0.68,1.36) p=0.60 for trend) but made minor differences to those with
      HF [p=0.05]. Leptin related positively to mortality in men without HF but
      inversely to mortality in those with HF; adjustment for leptin abolished the BMI
      mortality association in men with HF [HR 0.82 (0.31,2.20) and 0.99 (0.27,3.71);
      p=0.98 for trend]. CONCLUSION: The lower mortality risk associated with excess
      weight in men with CHD without HF may be due to higher muscle mass. In men with
      HF, leptin (possibly reflecting cachexia) explain the inverse association.

PMID- 24331122
TI  - Factors affecting supination strength after a distal biceps rupture.
AB  - HYPOTHESIS: This study quantified pain (visual analog pain scale [VAPS]),
      disability (Disabilities of the Arm, Shoulder and Hand [DASH]) and isometric
      supination torque at 3 forearm positions in a prospective cohort of biceps
      deficient arms to assess the potential for functional return with nonoperative
      treatment. MATERIALS AND METHODS: Twenty-three men (50 +/- 11 years) with
      complete unilateral distal biceps avulsion underwent isometric supination
      strength testing of both limbs at 60 degrees  of supination, 0 degrees 
      (neutral), and 60 degrees  of pronation. After exclusion of 1 outlier patient,
      the mean time from injury to evaluation was 44 days (range, 4-455 days). Pain
      level (VAPS) and functional outcome (DASH) were assessed; supination strength was
      normalized to the uninjured arm. RESULTS: The uninjured arm was stronger (P <
      .001), and peak torque varied with forearm position (P < .043). Peak torque was
      greater in pronation compared with supination, regardless of injury (P < .002).
      No differences were detected in supination strength as a result of forearm
      position or arm dominance. Supination strength did not correlate with time from
      injury to evaluation. One patient regained supination strength (115%) at 60
      degrees  of pronation and 72% in neutral with a lengthy time from injury. VAPS (5
      of 10) and DASH (39 of 100) scores decreased with time and did not relate to
      supination strength. CONCLUSION: Biceps tendon rupture led to a 60% decrease in
      supination strength in the neutrally oriented forearm. Peak torque observations
      can be explained using forearm moment arms. VAPS and DASH scores decreased with
      time but did not affect strength. We speculate that supination strength from
      pronation to neutral can improve as one strengthens the brachioradialis but
      strength deficits from neutral to supination are more difficult to overcome.

PMID- 24331123
TI  - Aseptic loosening rate of the humeral stem in the Coonrad-Morrey total elbow
      arthroplasty. Does size matter?
AB  - BACKGROUND: Aseptic implant loosening is one of the most common complications
      leading to revision surgery in total elbow arthroplasty. Different humeral stem
      lengths are available with varying designs. In general, the decision of which
      stem length to use depends on the surgical diagnosis or simply the surgeon
      preference. Often, the longer stem is used for post-traumatic or revision cases
      while for rheumatoid patients the shorter stem is preferred. There are no data in
      the literature to favor one humeral stem size over the other according to the
      diagnosis. METHODS: We analyzed the total elbow joint database of the Coonrad
      Morrey design at our institution for aseptic loosening leading to revision and
      compared the revision rate and the survival of the 4- and 6-inch humeral stems.
      RESULTS: Overall, revision for aseptic humeral loosening is infrequent and
      occurred in only 16 of 711 total elbow arthroplasties during a mean follow-up of
      88 months. There was no significant difference in the revision rate between the 2
      stem lengths (1.9% for the 4-inch stems and 2.6% for the 6-inch stem).
      CONCLUSION: Revision rate was correlated to the surgical diagnosis and was
      significantly higher for post-traumatic patients than for rheumatoid patients
      (5.1% vs 0.66%, P < .001). Of interest, and possibly not surprising, the mean
      time to revision was shorter for the 4-inch stems than it was for the 6-inch
      stems (37 vs 95 months, P = .034).

PMID- 24331124
TI  - Anatomic study of the flexor carpi ulnaris muscle and its application to soft
      tissue coverage of the elbow with clinical correlation.
AB  - BACKGROUND: The posterior elbow is prone to soft tissue loss that may require
      reconstructive methods for wound healing to be achieved. The flexor carpi ulnaris
      (FCU) muscle has been described for coverage in case reports and small series.
      Previous studies give conflicting anatomic findings about the dominant vascular
      pedicle for the FCU. METHODS: Twenty-five cadaveric specimens were dissected.
      Pedicle location, number, and distance from the medial epicondyle were recorded
      along with the extent of posterior elbow coverage. Chart review was conducted
      during a 4-year period. Eight patients who underwent FCU rotational flap coverage
      were identified. Those flaps relied entirely on a single proximal pedicle.
      RESULTS: The vascular pedicles from the ulnar artery or recurrent ulnar artery
      were identified in 24 of 25 specimens. The average distance from the tip of the
      medial epicondyle to the first pedicle was 5.7 cm (range, 3 to 10 cm). The length
      of muscle coverage proximal to the olecranon tip averaged 9.3 cm. The clinical
      follow-up of 7 patients requiring FCU rotational flaps for coverage of the
      posterior elbow showed that all flaps survived and provided adequate coverage for
      the defect. CONCLUSIONS: The FCU rotational pedicle flap provides predictable
      coverage of small to medium-sized defects about the posterior elbow. Although it
      is relatively consistent, the proximal vascular pedicle does demonstrate some
      variability, which should be considered in planning surgery. The consistent
      distal extent of the FCU muscle belly provides wider proximal coverage of
      defects.

PMID- 24331125
TI  - The effect of exercise-based management for multidirectional instability of the
      glenohumeral joint: a systematic review.
AB  - BACKGROUND: The most commonly recommended treatment for multidirectional
      instability (MDI) of the glenohumeral joint is exercise-based management. The
      primary objective of this review was to evaluate the effectiveness of exercise
      based management in patients with MDI. The secondary aim was to observe the types
      of exercise protocols and outcomes used, as well as any adverse results
      associated with exercise. METHODS: The Cochrane Database of Systematic Reviews,
      Medline, Embase, CINAHL (Cumulative Index to Nursing and Allied Health
      Literature), PEDro, Current Contents, Allied and Complementary Medicine (AMED),
      Australasian Medical Index (AMI), Ausport, and Clinical Trials Registers were
      searched for published and unpublished studies from the inception date to June
      2012 using the keywords multidirectional instability, glenohumeral, and exercise.
      Selection criteria included all study designs (except case reports and case
      series) and participants with clinically diagnosed MDI using exercise-based
      management. Inclusion criteria were not limited by outcomes. The authors' own
      risk-of-bias tool was used for quality assessment of studies. The GRADE approach
      (Grading of Recommendations, Assessment, Development and Evaluation) was used to
      synthesize the evidence. RESULTS: The risk of bias was high in all 7 included
      studies. For before-and-after comparisons of exercise-based management, GRADE
      assessment showed very low-quality evidence for improvements in shoulder
      kinematics, the Rowe score, overall status rating, and peak muscle strength.
      CONCLUSIONS: The effect of exercise-based management on MDI was variable across
      the included studies because of study heterogeneity and a high level of bias.
      There is a need for high-quality intervention studies to be undertaken to
      validate the effect of exercise for MDI.

PMID- 24331126
TI  - Treatment of osteoid osteoma of the elbow by radiofrequency thermal ablation.
AB  - BACKGROUND: This article presents the experience at the Rizzoli Orthopaedic
      Institute in the treatment of intracapsular osteoid osteoma (OO) of the elbow by
      computed tomography-guided percutaneous radiofrequency thermal ablation (RFA).
      MATERIALS AND METHODS: Our team performed more than 800 RFA procedures to treat
      OO up to 2010. In 27 cases, the lesion site was the articular area of the elbow
      (humerus in 13 cases, ulna in 13, and radius in 1). These patients were reviewed
      and assessed for eradication rate, incidence of complications, and functional
      results measured by the Mayo Elbow Performance Score. The outcome was evaluated
      after a mean follow-up period of 67.4 +/- 35.3 months (range, 24-128 months).
      RESULTS: The mean duration of symptoms at the time of diagnosis was 31.0 +/- 19.8
      months (range, 5-72 months). All patients complained about pain, and in 24 of 27
      cases (88.8%), the joint function was significantly impaired by the presence of
      OO (pretreatment score, 54.8). After RFA, the Mayo Elbow Performance Score
      improved by a mean of 37.7 +/- 14.8 points, with 25 of 27 patients (92.5%)
      scoring 90 to 100 points at final follow-up. OO recurred in only 1 patient
      (3.7%), 5 months after the procedure. However, this was successfully retreated by
      RFA. No adverse effects were observed, and all patients were free of disease at
      the final follow-up. DISCUSSION: The RFA procedure can be technically challenging
      in difficult sites such as the elbow joint. The low invasiveness of RFA compared
      with traditional surgery allows excellent functional recovery. RFA of elbow OO is
      effective and safe, and it should be considered the first-choice treatment for
      this disease.

PMID- 24331127
TI  - Enterobius vermicularis and allergic conditions in Norwegian children.
AB  - Studies investigating the association between Enterobius vermicularis and
      allergic conditions have shown conflicting results. This study was conducted to
      test for any such associations in Norwegian children. Parents were asked to
      answer questionnaires concerning their children's history of allergies, wheezing
      or eczema and pinworm infections. Current pinworm infections were diagnosed by
      microscopic examination of anal scotch tape samples. The data were analysed using
      logistic regression. Atopic eczema, allergy or wheezing was reported to be
      confirmed by a physician in 23% of the children (84/364). A possible association
      between current pinworm infections and food allergy was found, with 17.5% of
      children without food allergy testing positive for pinworms, compared to 36.8% of
      children with food allergy (odds ratio 2.9, 95% confidence interval 1.1-8.0). No
      association was found between past pinworm treatments and present atopic
      conditions. The association between current E. vermicularis infections and food
      allergy warrants further study.

PMID- 24331128
TI  - Sentinel lymph node status in vulval cancer: systematic reviews of test accuracy
      and decision-analytic model-based economic evaluation.
AB  - BACKGROUND: Vulval cancer causes 3-5% of all gynaecological malignancies and
      requires surgical removal and inguinofemoral lymphadenectomy (IFL). Complications
      affect > 50% of patients, including groin wound infection, lymphoedema and
      cellulitis. A sentinel lymph node (SLN) is the first groin node with the highest
      probability of malignancy. SLN biopsy would be useful if it could accurately
      identify patients in whom cancer has spread to the groin, without removing all
      groin nodes. SLNs can be identified by isosulfan blue dye and/or technetium-99
      ((99m)Tc) radioactive tracer during lymphoscintigraphy. The blue dye/(99m)Tc
      procedure only detects SLN, not metastases - this requires histological
      examination, which can include ultrastaging and staining with conventional
      haematoxylin and eosin (H&E) or immunohistochemistry. OBJECTIVES: To determine
      the test accuracy and cost-effectiveness of the SLN biopsy with (99m)Tc and/or
      blue dye compared with IFL or clinical follow-up for test negatives in vulval
      cancer, through systematic reviews and economic evaluation. DATA SOURCES:
      Standard medical databases, including MEDLINE, EMBASE, Science Citation Index and
      The Cochrane Library, medical search gateways, reference lists of review articles
      and included studies were searched to January 2011. METHODS: For accuracy and
      effectiveness, standard methods were used and reported according to Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      Searches were to January 2011, with no language restrictions. Meta-analyses were
      carried out with Meta-Disc version 1.4 (Javier Zamora, Madrid, Spain) for
      accuracy; none was appropriate for effectiveness. The economic evaluation from a
      NHS perspective used a decision-tree model in DATA TreeAge Pro Healthcare 2001
      (TreeAge Software, Inc., Williamstown, MA, USA). Six options (blue dye with H&E,
      blue dye with ultrastaging, (99m)Tc with H&E, (99m)Tc with ultrastaging, blue
      dye/(99m)Tc with H&E, blue dye/(99m)Tc with ultrastaging) were compared with IFL.
      Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: For
      accuracy, of the 26 included studies, most evaluated (99m)Tc/blue dye combined.
      Four studies had clinical follow-up only for test negatives and five had clinical
      follow-up for all and IFL for test negatives. Numbers with no SLN found were
      difficult to distinguish from those with negative SLN biopsies. The largest group
      of 11 studies using (99m)Tc/blue dye, ultrastaging and immunohistochemistry had a
      pooled sensitivity of 95.6% [95% confidence interval (CI) 91.5% to 98.1%] and a
      specificity of 100% (95% CI 99.0% to 100%). Mean SLN detection rates were 94.6%
      for (99m)Tc, 68.7% for blue dye and 97.7% for both. One study measured global
      health status quality of life (QoL) and found no difference between SLN biopsy
      and IFL. One patient preference evaluation showed that 66% preferred IFL rather
      than a 5% false-negative rate from SLN biopsy. For effectiveness, of 14,038
      references, one randomised controlled trial, three case-control studies and 13
      case series were found. Approximately 50% died from vulval cancer and 50% from
      other causes during follow-ups. Recurrences were in the ratio of approximately 4
      : 2 : 1 vulval, groin and distant, with more recurrences in node-positive
      patients. No studies reported QoL. For cost per death averted, IFL was less
      costly and more effective than strategies using SLN biopsy. For morbidity-free
      survival and long-term morbidity-free survival, (99m)Tc with ultrastaging was
      most cost-effective. Strategies with blue dye only and H&E only were never cost
      effective. The incremental cost-effectiveness ratio for (99m)Tc with ultrastaging
      compared with IFL was L4300 per case of morbidity-free survival and L7100 per
      long-term morbidity-free survival. LIMITATIONS: The main limitations of this
      study include the lack of good-quality evidence on accuracy, effectiveness and
      QoL. A large project such as this takes time to publish, so the most recent
      studies are not included. CONCLUSIONS: A sensitive and specific combined
      metastatic SLN detection test and information on generic QoL in vulval cancer is
      urgently required. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 24331129
TI  - The relationship between abdominal obesity and depression in the general
      population: A systematic review and meta-analysis.
AB  - SUMMARY: Obesity has been widely regarded as a public health concern because of
      its adverse impact on individuals' health. Systematic reviews have been published
      in examining the effect of obesity on depression, but with major emphasis on
      general obesity as measured by the body mass index. Despite a stronger effect of
      abdominal obesity on individuals' physical health outcomes, to our best
      knowledge, no systematic review was undertaken with regard to the relationship
      between abdominal obesity and depression. This paper reports the results of a
      systematic review and meta-analysis of cross-sectional studies examining the
      relationship between abdominal obesity and depression in a general population.
      Multiple electronic databases were searched until the end of September 2009. 15
      articles were systematically reviewed and meta-analyzed. The analysis showed that
      the odds ratio of having depression for individuals with abdominal obesity was
      1.38 (95% CI, 1.22-1.57) as compared to those who are not obese. Furthermore, it
      was found that this relationship did not vary with potential confounders
      including gender, age, measurement of depression and abdominal obesity, and study
      quality.:

PMID- 24331130
TI  - Reduced masticatory function in non-elderly obese Japanese adults.
AB  - SUMMARY:  OBJECTIVES: Abnormal eating behaviors such as compulsive overeating,
      eating fast, chewing less, palatable soft food preferences and avoiding hard food
      are often observed in obese individuals, and these behaviors may affect their
      masticatory function, but little information of masticatory function in obese
      subjects are available at present. The present study investigated masticatory
      function in non-elderly obese Japanese adults and explored the relationships
      between obesity and masticatory function. METHODS: Seventy-five obese subjects
      (BMI >= 25; male: 34, female: 41) and 98 subjects with normal weight (BMI 18.5
      25; male: 63, female: 35) aged 25-40 years old were enrolled in the present
      study. The status of masticatory function was determined using a chewing gum
      mixing method, a direct method of examining masticatory function, and the numbers
      of present teeth, untreated decayed teeth, missing teeth, and filled teeth were
      also examined. RESULTS: Masticatory function was significantly lower in the obese
      subjects both in male and female, whereas the numbers of present teeth, decayed
      teeth, missing teeth and filled teeth did not differ significantly between the
      obese subjects and the controls both in male and female. Multiple regression
      analysis revealed a significant correlation between obesity and reduced
      masticatory function after adjustment for gender, age, and numbers of decayed
      teeth, missing teeth, and filled teeth. CONCLUSIONS: Significantly reduced
      masticatory function was found in male and female non-elderly obese adults based
      on direct measurement of masticatory function. Multiple regression analysis
      suggested that obesity might induce reduced masticatory function.

PMID- 24331131
TI  - Relationship of body fat weight and body fat ratio determined by bioelectric
      impedance to serum adipocytokines in patients with type 2 diabetes mellitus.
AB  - SUMMARY:  OBJECTIVE: Various adipocytokines are closely associated with both
      obesity and insulin resistance. We investigated how body fat weight (BFW) and
      body fat ratio (BFR) affected serum adipocytokines in patients with type 2
      diabetes mellitus. METHODS: Studies were conducted in type 2 diabetic patients (n
      = 41) and age-matched healthy subjects (n = 18). BFW and BFR were determined
      using a high-frequency bioelectric impedance method. We measured the
      adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-alpha
      in serum. RESULTS: BFW and BFR showed significant positive correlations with BMI
      and serum leptin concentrations in diabetic patients. A significant positive
      correlation was found between BFW and serum FFA. Multivariate analysis identified
      only BMI a significant independent determinant of BFW. Stepwise analysis
      disclosed a significant positive correlation between HOMA-R and serum leptin.
      CONCLUSIONS: In diabetic patients, accumulation of body fat may increase serum
      leptin and FFA, which in turn would contribute to insulin resistance.

PMID- 24331132
TI  - Heart rate recovery after treadmill exercise testing is an independent predictor
      of stroke incidence in men with metabolic syndrome.
AB  - SUMMARY:  BACKGROUND AND AIMS: Heart rate recovery (HRR), a measure of the heart
      rate which decreases after a graded exercise test, has been associated with
      mortality and cardiovascular diseases. However, the association between HRR and
      risk of stroke has not been fully determined in men with metabolic syndrome
      (MetS). METHODS: Participants were 3886 men with MetS, aged 40-79 years, who
      completed a maximal exercise test during 1979-2004. We calculated 5-min HRR as
      the primary predictor and identified HRR tertiles; tertile 1 (<59 bpm), tertile 2
      (59-71 bpm), and tertile 3 (>71 bpm). Stroke incidence was ascertained from
      responses to mail-back surveys during 1982-2004. Differences in baseline
      characteristics across HRR tertiles were examined using general linear model.
      Hazard ratios (HRs) and 95% confidence intervals (95% CIs), were estimated using
      Cox regression model after adjusted for potential confounders. RESULTS: We
      identified 90 incident stroke cases during an average follow-up of 15.2 years.
      After adjusting for age-, examination year-, and survey response indicator, a
      significant inverse association between HRR and incident stroke was observed in
      men with MetS (p < 0.001). Compared with the lowest tertile of HRR, adjusted HRs
      in the second and third tertiles were 0.96 (0.53-1.74) and 0.41 (0.20-0.87),
      respectively. We also found a significant linear trend (p < 0.03) across
      increments of HRR. CONCLUSION: Delayed HRR was independently associated the
      higher risk of incident stroke in men with MetS. This suggests that HRR have
      prognostic value of stroke risk for men with MetS.

PMID- 24331133
TI  - Herbal delivery system for treatment of obesity administration of encapsulated
      khat-extracts on body weight of rats.
AB  - SUMMARY: Obesity is one of the most important problems worldwide. Khat (Catha
      edulis), an evergreen shrub, is thought to reduce body-weight. Its effect is more
      prominent when khat leaves are chewed. Thus, anti-obesity effects of khat and its
      associated side effects may depend on the release rate of its active
      constituents. The present study aimed to investigate the effect of a selected low
      dose of dried-khat, extracted, formulated as controlled release delivery systems
      on the body weight (BW), food intake (FI), cholesterol (CS) and triglyceride (TG)
      levels in rats. Khat extract (KE) was microencapsulated (KE235) and formulated
      into a parenteral implant (InjKE235). The effects of KE, KE235 and InjKE235 on
      BW, FI, CS and TG in rats were investigated. The results showed that
      microcapsules sustained the khat alkaloid release with T50% 1.58 h for KE235 and
      14.41 days for InjKE235. KE and KE235 caused maximum reduction in BW, FI, CS and
      TG during the first to third weeks but rebound gradually thereafter. On the
      contrary, InjKE235 exhibited a sustained reduction in BW, FI, CS and TG levels
      for 2 months. The T50% of KE, KE235 and InjKE235 correlated with the reduction in
      BW, CS and TG but not with FI. In conclusion, the subcutaneous injection and
      sustained release rate of khat extract play an important role in enhancing the
      anti-obesity effect in SD rats.:

PMID- 24331134
TI  - Predictive equation of resting energy expenditure in obese adult Taiwanese.
AB  - SUMMARY:  OBJECTIVE: To examine the accuracy of present resting energy
      expenditure (REE) predictive equations among obese adult Taiwanese, and obtain
      new predictive equations for this population. METHOD: A total of 80 participants
      (men = 42, women = 38) aged 18-64 years (mean 41.5 +/- 13.1 years) with body mass
      index (BMI) >=30 kg/m(2) were recruited from obesity clinic of a tertiary
      hospital. Anthropometric data including weight, height, waist circumference (WC),
      hip circumference (HipC) were collected. Body fat and fat free mass (FFM) were
      measured using bioelectric impedance analysis. Indirect calorimeter (Vmax 29n)
      was used for measurement of REE. The commonly used predictive equations (Harris
      Benedict equation, Bernstein equation, Mifflin equation, Owen equation, Schofield
      equation, Cunningham equation, Wang equation, and Liu equation) were tested for
      group means and individual prediction accuracy for our target population. New
      predictive equations were formulated using multiple linear regression analyses.
      RESULT: The mean BMI was 34.3 +/- 4.6 kg/m(2). All of the commonly used
      predictive equations showed statistically significant differences with the
      measured REE values. As for individual prediction accuracy, these predictive
      equations showed poor performance and only Mifflin equation provided an
      individual accuracy over 40%. The new predictive equation recommended for obese
      adult Taiwanese is below: REE (kcal/d) = 11.6 * weight (kg) - 204.84 * gender -
      4.8 * height (cm) + 1594.6 (gender: men = 1; women = 2). CONCLUSION: The previous
      commonly used predictive equations were less accurate in obese Taiwanese. For
      this specific population, the newly developed equation should be applied for
      better prediction of REE.

PMID- 24331135
TI  - Obesity trends by ethnicity in Hawai'i: The last ten years (1999-2008).
AB  - SUMMARY: Obesity levels are rising rapidly in United States of America however,
      less is known about the obesity trends regarding the specific ethnicities
      prevalent in Hawai'i, which may inform efforts to eliminate disparities.:
      OBJECTIVE: The purpose of this report is to analyze the body mass index (BMI)
      trends of the four major ethnicities in Hawai'i (White, Japanese, Hawaiian, and
      Filipino) over the last ten years. METHOD: The BMI data overall and by ethnicity
      from 1999 to 2008 were utilized from the Behavioral Risk Factor Surveillance
      System (BRFSS). RESULTS: We found that all ethnicities experienced a 47% increase
      in mean percent of obese persons. The Hawaiian ethnic group had the largest
      number of obese individuals, but they experienced the smallest increase. The
      Filipino ethnic group had less obese individuals, but they experienced the
      largest percentage increase. CONCLUSION: Based on these findings, obesity
      prevention efforts aimed at Hawai'i's multicultural population need to be
      improved and increased.

PMID- 24331136
TI  - Telmisartan effectively improves insulin sensitivity in hypertensive patients
      with insulin resistance.
AB  - SUMMARY:  OBJECTIVE: The angiotensin II receptor blocker (ARB) telmisartan has
      been shown to activate peroxisome proliferator-activated receptor gamma and
      increase adiponectin protein content in adipocytes. We tested the hypothesis that
      telmisartan can increase the serum level of adiponectin and improve insulin
      resistance. METHODS: The study participants were 25 consecutive hypertensive
      patients (8 females, 17 males; 65 +/- 10 years). Insulin resistance was defined
      as a patient showing >=2.5 in the homeostasis model assessment (HOMA) index. We
      divided subjects into non-insulin resistance (n = 10) and insulin resistance
      groups (n = 15) based on the HOMA index. Telmisartan was administered (40 mg/day)
      was administered for 24 weeks. RESULTS: In the insulin resistance group,
      telmisartan treatment resulted in a significant decrease in the HOMA index and
      serum level of C-reactive protein, and it increased the serum level of
      adiponectin (P < 0.05, respectively). Such improvements were not observed in the
      non-insulin resistance group. Stepwise multiple regression analysis showed that
      the increase in the serum level of adiponectin was independently associated with
      reduction in the HOMA index. CONCLUSIONS: Our findings suggest that telmisartan
      improves insulin resistance that parallels an increase in the serum level of
      adiponectin in hypertensive patients with insulin resistance. It may therefore
      have advantages in treating such populations.

PMID- 24331137
TI  - Fenofibrate ameliorates insulin resistance, hypertension and novel oxidative
      stress markers in patients with metabolic syndrome.
AB  - SUMMARY:  OBJECTIVE: The benefits of fenofibrate, a peroxisome proliferator
      activated receptor alpha agonist, against cardiovascular risk factors have been
      established. To clarify the underlying mechanisms of these benefits, we examined
      the effects of fenofibrate on insulin resistance, hypertension, inflammation,
      oxidative stress and coagulation markers in patients with metabolic syndrome.
      METHODS: Eleven Japanese patients with metabolic syndrome underwent physical
      examinations and blood tests before and after treatment with fenofibrate 200 mg
      daily for 8 weeks. RESULTS: Fenofibrate significantly decreased systolic blood
      pressure, pulse wave velocity, serum insulin, insulin resistance (calculated from
      the homeostasis model assessment), total cholesterol, triglyceride, remnant-like
      particles cholesterol, uric acid, D-dimer, fibrinogen, serum amyloid A/low
      density lipoprotein (LDL) and apoA1/LDL levels. It also significantly increased
      levels of high molecular weight adiponectin, thrombomodulin and high-density
      lipoprotein cholesterol in these patients. Plasminogen activator inhibitor-1, C
      reactive protein, fasting plasma glucose and thrombin-antithrombin complex levels
      did not change. LIMITATION: Small sample size. CONCLUSION: Short-term fenofibrate
      administration not only improved lipid profiles, but also ameliorated insulin
      resistance, hypertension and oxidative stress markers in patients with metabolic
      syndrome, suggesting that fenofibrate can decrease the risk of arteriosclerosis
      through various pathways.

PMID- 24331138
TI  - Perceptions of obesity in self and others.
AB  - SUMMARY:  OBJECTIVE: To explore the effects of social conditioning in an obese
      population on self-perception and beliefs about the causes of obesity for self
      and others. PARTICIPANTS AND DESIGN: Eighty-seven obese adults (29 males and 58
      females) aged between 18 and 66 years from an Australian metropolitan hospital's
      obesity clinic and 50 healthy weight adults (15 males and 35 females) aged
      between 17 and 45 years from two undergraduate university courses participated in
      a cross-sectional study. RESULTS: Obese participants were more likely to
      attribute internal factors as the cause of obesity in others (X(2)(1, n = 77) =
      24.6, p <= 0.001) but considered internal and external factors equally as causing
      their own obesity (X(2)(1, n = 80)=.02, p >= 0.05). Weight locus of control was
      not related to body size in obese participants however, it was related to
      psychological well-being (r = -0.38, n = 68, p <= 0.005). Obese participants were
      unable to accurately identify their own current (t(83) = 84.54, p <= 0.01) and
      desired body shape (t(85) = 50.16, p <= 0.01). Significant differences were
      present when rating female body shapes, with female obese participants unable to
      accurately identify body shapes compared to the healthy weight controls.
      Additionally, female perceptions of overweight appear to be normalising; they
      were unable to correctly discriminate between differing body shapes. Healthy
      weight males also exhibited this effect. CONCLUSIONS: Attribution of obesity to
      external factors is a likely barrier to weight loss, whilst a higher internal
      weight locus of control and associated psychological well-being may facilitate
      weight loss. Consideration of these factors may lead to better individual
      treatment outcomes. The normalisation of perceptions of weight, likely due to
      social conditioning, has implications for identification of at risk individuals
      and public health initiatives.

PMID- 24331139
TI  - Decreased plasma B-type natriuretic peptide levels in obesity are not explained
      by altered left ventricular hemodynamics.
AB  - SUMMARY:  BACKGROUND: Although obesity has been reported to be associated with
      decreased plasma B-type natriuretic peptide (BNP) levels, it is unknown whether
      the reduced BNP levels in obesity results from decreased left ventricular (LV)
      hemodynamic load. METHODS: We examined the relationships between body mass index
      (BMI), plasma BNP levels, and LV systolic and diastolic function (ejection
      fraction [EF] and end-diastolic pressure [EDP]) in 271 consecutive patients
      undergoing cardiac catheterization for coronary artery disease. When patients
      were grouped by tertile of BMI, with increasing tertiles of BMI, there was a
      progressive increase in EDP (lower, middle, and upper tertiles of BMI, 13.5 +/-
      5.8, 14.9 +/- 5.3, and 16.3 +/- 5.4 mmHg, respectively; p for trend <0.01) and a
      progressive decrease in log BNP levels (lower, middle, and upper tertiles of BMI,
      3.52 +/- 1.29, 2.96 +/- 1.08, and 2.87 +/- 1.21 ln[pg/ml], respectively, p for
      trend < 0.001). There was no clear difference in EF across BMI tertiles (p for
      trend >0.1). Plasma BNP levels correlated positively with EDP (r = 0.38, p <
      0.001). In multivariate linear regression including EDP and known correlates of
      plasma BNP levels, BMI correlated negatively with BNP levels (standardized beta =
      -0.31, p < 0.001). CONCLUSIONS: We found that increased BMI was associated with
      LV diastolic abnormalities without change in systolic function and that patients
      with increased BMI had reduced plasma BNP levels despite having elevated EDP.
      These results suggest that the reduced BNP levels in obesity are not explained by
      altered LV hemodynamics.

PMID- 24331140
TI  - Transcatheter aortic valve replacement: current status and future directions.
AB  - Transcatheter aortic valve replacement (TAVR) is a revolutionary therapy for
      patients with aortic stenosis. Large registries and randomized controlled trials
      have demonstrated that TAVR is safe and effective in patients considered
      inoperable because of severe comorbidities and those who are high-risk surgical
      candidates. As TAVR evolves for lower-risk patients, attention will need to focus
      on reducing the rates of vascular injury, stroke, and paravalvular regurgitation.
      In this review, we discuss the status of TAVR in clinical practice, including
      patient selection, preoperative evaluation, techniques, and complications. 

PMID- 24331141
TI  - Surgical treatment of atrial fibrillation: today's questions and answers.
AB  - Although atrial fibrillation is common in cardiac surgery patients, the Cox maze
      IV procedure is underutilized; in contemporary practice, most cardiac surgery
      patients with atrial fibrillation do not receive concomitant surgical ablation.
      Available evidence suggests that a biatrial, energy-assisted Cox maze IV
      procedure restores normal sinus rhythm in two-thirds to three-quarters of
      patients without increasing operative risk. The best results are obtained by
      adherence to the correct lesion set and careful attention to perioperative
      management of heart rhythm and anticoagulation. To date, we have no randomized
      clinical trials confirming that surgical ablation improves clinical outcomes
      beyond restoration of sinus rhythm; however, available evidence does suggest that
      concomitant surgical ablation provides clinical benefit, most notably by reducing
      the long-term risk of stroke. 

PMID- 24331142
TI  - Surgical management of tetralogy of fallot: in defense of the infundibulum.
AB  - Surgical treatment of the Tetralogy of Fallot (ToF) is one of the great successes
      of medicine and also a topic of controversy. Different strategies have been
      proposed, including age-based (neonatal) management strategies as well as
      anatomic-based management strategies. Regardless of the management strategy
      entailed, the surgical management of ToF has considerably evolved over the years.
      As a result, patients can now expect excellent early results with survival
      approaching 100% for those without genetic syndromes. The goals of current
      surgical therapy should be to mitigate the late right ventricular (RV)
      dysfunction that may occur by minimizing the extent of surgical injury during the
      intial repair. As the surgical techniques continue to advance, the outcomes will
      continue to improve. 

PMID- 24331143
TI  - How to follow up patients after curative resection of lung cancer.
AB  - Survivors of lung cancer surgery are among the highest-risk patients for
      developing another lung cancer, yet there is no clear consensus on the method of
      surveillance for patients after curative surgical resection. Surveillance is no
      longer futile because the emergence of computed tomography screening has allowed
      the detection of recurrences and new metachronous cancers at an early stage. In
      selected patients, lung cancer identified recently on routine computed tomography
      scan is amenable to curative treatment and is associated with longer survival. 

PMID- 24331144
TI  - Invasive mediastinal staging: endobronchial ultrasound, endoscopic ultrasound,
      and mediastinoscopy.
AB  - Accurate mediastinal staging is essential to determining the optimal therapeutic
      strategy for many patients with lung cancer. Computed tomography and positron
      emission tomography are first steps, but frequently tissue sampling is
      recommended to confirm the radiographic findings. Mediastinoscopy has been the
      gold standard for thirty years, but the new technologies of esophageal endoscopic
      ultrasound and endobronchial ultrasound provide a less invasive method for
      biopsy. These techniques enable needle aspiration sampling of nearly all
      mediastinal and hilar lymph nodes, and experience with them is now sufficiently
      mature to conclude that they can be equivalent if not preferable to
      mediastinoscopy. The keys to achieving accurate results are skillful execution
      combined with sound clinical judgment regarding when to use which techniques.
      Patients with lung cancer are best served by clinicians experienced with all
      three methods for invasive mediastinal staging. 

PMID- 24331145
TI  - Current readings on off-pump coronary artery bypass.
AB  - Historically, the use of cardiopulmonary bypass (CPB) in performing coronary
      artery bypass grafting (CABG) has been the "gold standard" in coronary
      revascularization. However, with greater understanding of the inflammatory
      effects of CPB and the increased risks of strokes in atherosclerotic or calcified
      aortas, there has been a growing interest in less-invasive approaches to the
      standard conventional technique. One such approach is performing coronary
      revascularization without using CPB, also known as off-pump CABG (OPCAB). Several
      studies have reported that OPCAB is a safe and effective technique that avoids
      the significant morbidity associated with the use of CPB, whereas other studies
      report no overall advantage with the avoidance of CPB in coronary
      revascularization and a trend toward better outcomes in patients undergoing the
      conventional on-pump technique. The controversial topic of on-pump vs OPCAB has
      been the subject of ongoing debate for over a decade. This article reviews
      current literature and hopefully provides an unbiased guide for assessing the
      values, benefits, and risks of both the techniques. 

PMID- 24331146
TI  - Current readings: neurocognitive impairment and clinical implications after
      cardiac surgery.
AB  - The earliest reports of cardiac surgery literatures reported evidence of
      neurocognitive decline, highlighted in the 1995 statement of Consensus on
      assessment of neurobehavioral outcomes after cardiac surgery. Until now, the
      magnitude and clinical importance of neurocognitive outcomes continues to
      fluctuate and lack clarity. The aim of this review is to evaluate the
      contemporary status of neurocognitive outcomes in relation to pre-existing
      impairment, revascularization strategy, broader cardiovascular pathophysiological
      processes, and any longer-term clinical implications. Five studies published
      between 2009 and 2013 were reviewed. A meta-analysis did not find differences
      between on- and off-pump procedures. In other studies, there was evidence for
      extensive preoperative neurocognitive impairments. Additional 2 studies showed
      that longer-term neurocognitive impairment, including dementia, was not
      dissimilar to nonsurgical patients with cardiovascular disease. Currently, there
      is no convincing evidence to suggest that cardiac surgery, and cardiopulmonary
      bypass in particular, has a causal role in progression to dementia, or long-term
      deficit, independent of pre-existing neurocognitive impairments and
      cardiovascular disease. 

PMID- 24331147
TI  - Current readings: improvements in intensity-modulated radiation therapy for
      malignant pleural mesothelioma.
AB  - The treatment of malignant pleural mesothelioma with radiation therapy has always
      been a technical challenge. Early experience with intensity-modulated radiation
      therapy demonstrated troubling toxicity. Recent reports from institutions have
      demonstrated that with greater experience, intensity-modulated radiation therapy
      can be delivered safely, both in the setting of pneumonectomy or pleurectomy.
      After pneumonectomy, the dose to the contralateral lung must be minimized,
      preferably with a volume of lung receiving 20 Gy (V20) to less than 5% and a mean
      lung dose of approximately 10%. In the setting of 2 intact lungs, the mean lung
      dose can be as high as 20 Gy. Expected rates of grade 3 or worse radiation
      pneumonitis are 12%-20%. The rates of fatal pneumonitis are approximately 3%-8%
      in these studies, which demonstrate the considerable toxicity of treatment, even
      with improved technique.

PMID- 24331148
TI  - Current readings: the most influential and recent studies regarding resection of
      lung cancer in m1a disease.
AB  - M1A disease is a recent concept appearing in the 7th TNM classification of lung
      cancer. M1A encompasses two different entities, malignant pleural or pericardial
      effusions and separate tumor nodules in the contralateral lung, who constitute
      very different diseases, with very different management and prognoses. On one
      hand, patients with pleural dissemination have extremely poor survival, with
      median and 5-year survivals of 4 months and 3.1%, respectively. Only selected
      patients whose limited pleural extension has been diagnosed at the time of
      thoracotomy and completely resected, may experience prolonged survival. On the
      other hand, recent progress in molecular biology still failed to establish
      whether a contralateral lesion is a second primary or a metastasis. These
      contralateral lesions are now gathered as multiple lung cancers in the surgical
      literature, and misleadingly classified as M1A disease in the TNM classification.
      Patients with contralateral nodules may experience prolonged survival after the
      surgical treatment of both localizations. Changing the staging by establishing
      the diagnosis of metastasis is probably an important issue warranting further
      biologic research, but according to current results this diagnosis must not in
      any case preclude surgery. 

PMID- 24331149
TI  - Management of the Apical Tumor: May 4, 2013, Minneapolis, MN.

PMID- 24331150
TI  - A plea for higher-quality data for GreenLight laser technology in the context of
      surgical benign prostatic obstruction trials: the GOLIATH study-fact or fiction
      in the era of evidence-based urology?

PMID- 24331151
TI  - Gender-specific differences in clinicopathologic outcomes following radical
      cystectomy: an international multi-institutional study of more than 8000
      patients.
AB  - BACKGROUND: The impact of gender on the staging and prognosis of urothelial
      carcinoma of the bladder (UCB) is insufficiently understood. OBJECTIVE: To assess
      gender-specific differences in pathologic factors and survival of UCB patients
      treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: Data
      from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB
      between 1971 and 2012 were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Multivariable competing-risk regression analyses were performed to
      evaluate the relationship of gender on disease recurrence (DR) and cancer
      specific mortality (CSM). We also tested the interaction of gender and tumor
      stage, nodal status, and lymphovascular invasion (LVI). RESULTS AND LIMITATIONS:
      Female patients were older at the time of RC (p=0.033) and had higher rates of
      pathologic stage T3/T4 disease (p<0.001). In univariable, but not in
      multivariable analysis, female gender was associated with a higher risk of DR
      (p=0.022 and p=0.11, respectively). Female gender was an independent predictor
      for CSM (p=0.004). We did not find a significant interaction between gender and
      stage, nodal metastasis, or LVI (all p values >0.05). CONCLUSIONS: We found
      female gender to be associated with a higher risk of CSM following RC. However,
      these findings do not appear to be explained by gender differences in pathologic
      stage, nodal status, or LVI. This gender disparity may be due to differences in
      care and/or the biology of UCB.

PMID- 24331153
TI  - Re: Willem M. Brinkman, Irene M. Tjiam, Barbara M.A. Schout, et al. Results of
      the European basic laparoscopic urological skills examination. Eur Urol
      2014;65:490-6.

PMID- 24331152
TI  - 180-W XPS GreenLight laser vaporisation versus transurethral resection of the
      prostate for the treatment of benign prostatic obstruction: 6-month safety and
      efficacy results of a European Multicentre Randomised Trial--the GOLIATH study.
AB  - BACKGROUND: The comparative outcome with GreenLight (GL) photoselective
      vaporisation of the prostate and transurethral resection of the prostate (TURP)
      in men with lower urinary tract symptoms due to benign prostatic obstruction
      (BPO) has been questioned. OBJECTIVE: The primary objective of the GOLIATH study
      was to evaluate the noninferiority of 180-W GL XPS (XPS) to TURP for
      International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) at 6 mo
      and the proportion of patients who were complication free. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective randomised controlled trial at 29 centres in 9 European
      countries involving 281 patients with BPO. INTERVENTION: 180-W GL XPS system or
      TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Measurements used were IPSS,
      Qmax, prostate volume (PV), postvoid residual (PVR) and complications,
      perioperative parameters, and reintervention rates. Noninferiority was evaluated
      using one-sided tests at the 2.5% level of significance. The statistical
      significance of other comparisons was assessed at the (two-sided) 5% level.
      RESULTS AND LIMITATIONS: The study demonstrated the noninferiority of XPS to TURP
      for IPSS, Qmax, and complication-free proportion. PV and PVR were comparable
      between groups. Time until stable health status, length of catheterisation, and
      length of hospital stay were superior with XPS (p<0.001). Early reintervention
      rate within 30 d was three times higher after TURP (p=0.025); however, the
      overall postoperative reintervention rates were not significantly different
      between treatment arms. A limitation was the short follow-up. CONCLUSIONS: XPS
      was shown to be noninferior (comparable) to TURP in terms of IPSS, Qmax, and
      proportion of patients free of complications. XPS results in a lower rate of
      early reinterventions but has a similar rate after 6 mo. TRIAL REGISTRATION:
      ClinicalTrials.gov, identifier NCT01218672.

PMID- 24331155
TI  - Immunotherapy in non-small-cell lung cancer: a good start?

PMID- 24331156
TI  - Cognitive rehabilitation of memory for mild cognitive impairment: a
      methodological review and model for future research.
AB  - Several recent reviews have suggested that cognitive rehabilitation may hold
      promise in the treatment of memory deficits experienced by patients with mild
      cognitive impairment. In contrast to the previous reviews that mainly focused on
      outcome, the current review examines key methodological challenges that are
      critical for designing and interpreting research studies and translating results
      into clinical practice. Using methodological details from 36 studies, we first
      examine diagnostic variability and how the use of cutoffs may bias samples toward
      more severely impaired patients. Second, the strengths and limitations of several
      common rehabilitative techniques are discussed. Half of the reviewed studies used
      a multi-technique approach that precludes the causal attribution between any
      specific technique and subsequent improvement. Third, there is a clear need to
      examine the dose-response relationship since this information was strikingly
      absent from most studies. Fourth, outcome measures varied widely and frequently
      depended on neuropsychological tests with little theoretical justification or
      ecological relevance. Fifth, we discuss how the variability in each of these
      other four areas complicates efforts to examine training generalization. Overall,
      future studies should place greater emphasis on ecologically relevant treatment
      approaches and outcome measures and we propose a hierarchical model that may aid
      in this pursuit.

PMID- 24331157
TI  - Successful provision of emergency mental health care to rural and remote New
      South Wales: an evaluation of the Mental Health Emergency Care-Rural Access
      Program.
AB  - OBJECTIVE: To evaluate a rural emergency telepsychiatry program, the Mental
      Health Emergency Care-Rural Access Program (MHEC-RAP), which aims to improve
      access to emergency mental health care for communities throughout western New
      South Wales (NSW). METHODS: A descriptive analysis of service activity data from
      the introduction of the MHEC-RAP in 2008 to 2011 using Chi-squared tests and
      linear regression modelling to assess change and trends over time. RESULT: There
      were 55959 calls to the MHEC-RAP, 9678 (17%) of these calls initiated an MHEC-RAP
      service (~2500 each year). The use of video assessment increased over 18 months,
      then levelled off to an average of 65 each month. Health care provider use
      increased from 54% to 75% of all contacts, and 49% of MHEC-RAP patients were
      triaged 'urgent'. Most (71%) were referred from the MHEC-RAP for outpatient care
      with a local provider. The proportion of MHEC-RAP patients admitted to hospital
      initially increased by 12%, then declined over the next 2 years by 7% (by 28% for
      admissions to a mental health inpatient unit (MHIPU)). CONCLUSION: The MHEC-RAP
      is well established. It has achieved acceptable levels of service activity and
      continues to be as used as intended. Further research is required to confirm how
      the MHEC-RAP works in terms of process and capacity, how it has changed access to
      mental health care and to document its costs and benefits. WHAT IS KNOWN ABOUT
      THE TOPIC? Rural and remote communities have poorer access to and use of mental
      health services. Telehealth care is a reliable and accepted means for providing
      non-urgent mental health care. WHAT DOES THIS PAPER ADD? The MHEC-RAP is a
      practical and transferable solution to providing specialist emergency mental
      health care, and support for local providers, in rural and remote areas via
      telehealth. There is a possible impact upon the problem of recruiting and
      retaining a mental health workforce in rural and remote areas. WHAT ARE THE
      IMPLICATIONS FOR PRACTITIONERS? Providing reliable remote access to specialist
      mental health assessment and advice while supporting providers in rural
      communities can result in better outcomes for patients and services alike.

PMID- 24331159
TI  - Impact of socioeconomic status on initial clinical presentation to a memory
      disorders clinic.
AB  - BACKGROUND: Dementia affects 15% of Canadians 65 and older, and the prevalence is
      expected to double over the next two decades. Low socioeconomic status (SES) can
      increase the risk of Alzheimer's disease (AD) and the precursor mild cognitive
      impairment (MCI), but it is unknown what the relationship of SES is on initial
      clinical presentation to a memory disorders clinic. METHODS: Data from 127 AD and
      135 MCI patients who presented to our Memory Disorders Clinic from 2004 to 2013
      were analyzed retrospectively. We examined the relationship between SES (measured
      using Hollingshead two-factor index) and (1) diagnosis of either AD or MCI; (2)
      age when first presented to clinic; (3) objective cognitive tests to indicate
      clinical severity; and (4) the use of cognitive enhancers, medication for
      treating mild-to-moderate AD patients. RESULTS: AD patients had lower SES than
      MCI patients (p < 0.001, r = 0.232). Lower SES was associated with a greater age
      at initial time of diagnosis (chi2 = 11.5, p = 0.001). In MCI patients, higher
      SES individuals outperformed lower SES individuals on the BNA after correcting
      for the effect of age (p = 0.004). Lower SES was also associated with decreased
      use of cognitive enhancers in AD patients (p < 0.001, r = 0.842). CONCLUSION:
      Individuals with lower SES come into memory clinic later when the disease has
      progressed to dementia, while higher SES individuals present earlier when the
      disease is still in its MCI stage. There were more higher SES individuals who
      presented to our memory clinic. Higher SES is associated with better cognitive
      functioning and increased use of cognitive enhancers. The health policy
      implication is that we need to better engage economically disadvantaged
      individuals, perhaps at the primary care level.

PMID- 24331160
TI  - The effects of freezing, boiling and degreasing on the microstructure of bone.
AB  - The histology of bone has been a useful tool in research. It is commonly used to
      estimate the age of an individual at death, to assess if the bone is of human or
      non-human origin and in trauma analysis. Factors that affect the histology of
      bone include age, sex, population affinity and burning to name but a few. Other
      factors expected to affect bone histology are freezing, boiling and degreasing
      but very little information is available for freezing and the effect thereof, and
      it is unknown if boiling and degreasing affects bone histology. The aim of this
      study was to assess the effects of freezing, freezing and boiling, and freezing,
      boiling and degreasing on the histological structure of compact bone. Five
      cadaver tibiae were frozen at -20 degrees C for 21 days followed by segments
      being boiled in water for three days and degreased in trichloroethylene at 82
      degrees C for three days. Anterior midshaft sections were prepared as ground
      sections and for Scanning Electron Microscopy (SEM). Quantitatively, there were
      no significant differences between freezing, boiling and degreasing; however,
      qualitative differences were observed using SEM. After being frozen the bone
      displayed cracks and after boiling the bones displayed erosion pits on the
      surface. It is suggested that further research, using different durations and
      temperatures for boiling and freezing be undertaken on bone samples representing
      different ages and various skeletal elements. 

PMID- 24331161
TI  - Should "Disability Status" be a covariate in most epidemiologic research?

PMID- 24331162
TI  - Unintentional injuries among Chinese children with different types and severity
      of disability.
AB  - PURPOSE: Little research has been done in China to study injury in individuals
      with disability. We investigated the impact of type and severity of disability on
      injury among children with disability in Hubei Province of China. METHODS: A
      sample of 1201 children with disability were matched with 1201 healthy children
      on gender, age, and neighborhood. Disability type and severity were determined
      using the Chinese national standards. Caregivers were interviewed face-to-face
      about nonfatal unintentional injuries suffered by the child in the past 12 months
      before the interview. Univariate chi(2) test and logistic regression models were
      used to investigate association between disability type/severity and nonfatal
      unintentional injuries. RESULTS: Injury rate among children with disability was
      significantly higher than that among children without disability (10.2% vs. 4.4%;
      P < .001). Children with multiple disabilities had the highest risk of injury
      after controlling for confounding variables (odds ratio, 4.54; 95% confidence
      interval, 2.82-7.30; P < .001). The magnitude of the association between
      disability and injury varied by type and severity of disability. CONCLUSIONS: The
      magnitude of the association between the presence or absence of disability in
      children and their risk of injury was large and significant, regardless of the
      type or severity of the children's disabilities.

PMID- 24331163
TI  - Use of illicit stimulant drugs in Finland: a wastewater study in ten major
      cities.
AB  - Estimations of drug use at the national level are generally based on various
      sources of information, such as drug seizures, socio-scientific studies,
      toxicological data and hospital records. Nevertheless, all of these approaches
      have limitations that cannot be overcome, even if conclusions are drawn from
      combined data retrieved from different sources. Drug epidemiology through
      wastewater analysis has the potential to provide unique perspectives,
      internationally comparable data, and up-to-date information on the use of both
      traditional illicit drugs and new psychoactive substances (NPSs). In Finland, no
      large-scale studies on regional illicit drug consumption, based on a wastewater
      approach, have been reported. In this study, 24-h influent composite samples were
      collected during two 1-week study periods from ten different wastewater treatment
      plants in May and November-December 2012. The cities included in the study
      represent the geographical areas throughout Finland and cover 40% of the Finnish
      population. The samples were analyzed with an in-house validated, ultra high
      performance liquid-chromatography mass spectrometric (UHPLC-MS/MS) method for
      various common illicit drugs and some NPS type stimulant drugs. The results were
      also compared with available statistics, information on drug seizures and
      laboratory-confirmed toxicological data, as well as other studies available based
      on wastewater analysis. The data show that illicit stimulant drug use is more
      common in the larger cities of Southern Finland. Amphetamine was the most
      commonly used drug in all 10 cities during both collection periods (excluding the
      collection period in May in Lappeenranta). Cocaine consumption remains very low
      in Finland in comparison to other European countries; it was concentrated in the
      biggest cities in Southern Finland. This study shows interesting temporal and
      spatial differences in drug use in Finland, as well as the possibilities of using
      wastewater analytics to reveal local hotspots of NPS consumption. 

PMID- 24331165
TI  - Trends in insurance coverage and source of private coverage among young adults
      aged 19-25: United States, 2008-2012.
AB  - KEY FINDINGS: Data from the National Health Interview Survey, 2008-2012. The
      percentage of young adults with private health insurance coverage increased from
      the last 6 months of 2010 through the last 6 months of 2012 (52.0% to 57.9%).
      Except for an increase in the first 6 months of 2011, the percentage of privately
      insured young adults who had a gap in coverage during the past 12 months
      decreased from the first 6 months of 2008 through the last 6 months of 2012
      (10.5% to 7.8%). The percentage of privately insured young adults with coverage
      in their own name decreased from 40.8% in the last 6 months of 2010 to 27.2% in
      the last 6 months of 2012. The percentage of privately insured young adults with
      employer-sponsored health insurance increased from the last 6 months of 2010 to
      the last 6 months of 2012 (85.6% to 92.5%). Young adults often experience
      instability with regard to work, school, residential status, and financial
      independence. This could contribute to a lack of or gaps in insurance coverage
      (1,2). In September 2010, the Affordable Care Act (ACA) extended dependent health
      coverage to young adults up to age 26. This provision was expected to lead to
      increases in private coverage for young adults aged 19-25 when they became
      eligible for coverage through their parents' employment (3,4). This report
      provides estimates describing the previous insurance status and sources of
      coverage among privately insured young adults aged 19-25, using data from the
      2008-2012 National Health Interview Survey (NHIS). Comparisons are made with
      adults aged 26-34, the most similar age group that was not affected by the ACA
      provision.

PMID- 24331164
TI  - Improved microchip design and application for in situ transmission electron
      microscopy of macromolecules.
AB  - Understanding the fundamental properties of macromolecules has enhanced the
      development of emerging technologies used to improve biomedical research.
      Currently, there is a critical need for innovative platforms that can illuminate
      the function of biomedical reagents in a native environment. To address this
      need, we have developed an in situ approach to visualize the dynamic behavior of
      biomedically relevant macromolecules at the nanoscale. Newly designed silicon
      nitride devices containing integrated "microwells" were used to enclose active
      macromolecular specimens in liquid for transmission electron microscopy imaging
      purposes.We were able to successfully examine novel magnetic resonance imaging
      contrast reagents, micelle suspensions, liposome carrier vehicles, and
      transcribing viral assemblies. With each specimen tested, the integrated
      microwells adequately maintained macromolecules in discrete local environments
      while enabling thin liquid layers to be produced. 

PMID- 24331154
TI  - Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non
      small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.
AB  - BACKGROUND: Effective maintenance therapies after chemoradiotherapy for lung
      cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific
      cancer immunotherapy tecemotide improves survival in patients with stage III
      unresectable non-small-cell lung cancer when given as maintenance therapy after
      chemoradiation. METHODS: The phase 3 START trial was an international,
      randomised, double-blind trial that recruited patients with unresectable stage
      III non-small-cell lung cancer who had completed chemoradiotherapy within the 4
      12 week window before randomisation and received confirmation of stable disease
      or objective response. Patients were stratified by stage (IIIA vs IIIB), response
      to chemoradiotherapy (stable disease vs objective response), delivery of
      chemoradiotherapy (concurrent vs sequential), and region using block
      randomisation, and were randomly assigned (2:1, double-blind) by a central
      interactive voice randomisation system to either tecemotide or placebo.
      Injections of tecemotide (806 MUg lipopeptide) or placebo were given every week
      for 8 weeks, and then every 6 weeks until disease progression or withdrawal.
      Cyclophosphamide 300 mg/m(2) (before tecemotide) or saline (before placebo) was
      given once before the first study drug administration. The primary endpoint was
      overall survival in a modified intention-to-treat population. This study is
      registered with ClinicalTrials.gov, number NCT00409188. FINDINGS: From Feb 22,
      2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide
      and 507 to placebo). 274 patients were excluded from the primary analysis
      population as a result of a clinical hold, resulting in analysis of 829 patients
      in the tecemotide group and 410 in the placebo group in the modified intention-to
      treat population. Median overall survival was 25.6 months (95% CI 22.5-29.2) with
      tecemotide versus 22.3 months (19.6-25.5) with placebo (adjusted HR 0.88, 0.75
      1.03; p=0.123). In the patients who received previous concurrent
      chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients
      assigned to tecemotide was 30.8 months (95% CI 25.6-36.8) compared with 20.6
      months (17.4-23.9) for the 268 (65%) of 410 patients assigned to placebo
      (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received previous
      sequential chemoradiotherapy, overall survival did not differ between the 291
      (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo
      group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0], respectively;
      adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen with a
      greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients
      in the tecemotide group vs 21 [4%] of 477 patients in the placebo group),
      metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%]
      vs 12 [3%]). Serious adverse events with a greater than 2% frequency with
      tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the
      placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous
      system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ
      between groups. INTERPRETATION: We found no significant difference in overall
      survival with the administration of tecemotide after chemoradiotherapy compared
      with placebo for all patients with unresectable stage III non-small-cell lung
      cancer. However, tecemotide might have a role for patients who initially receive
      concurrent chemoradiotherapy, and further study in this population is warranted.
      FUNDING: Merck KGaA (Darmstadt, Germany).

PMID- 24331166
TI  - Delayed exstrophy repair (DER) does not compromise initial bladder development.
AB  - OBJECTIVE: Delayed exstrophy repair (DER) represents an alternative to early
      neonatal bladder closure. This study aims to define the consequence of DER on
      bladder growth in bladder exstrophy patients who underwent routine DER, compared
      with those who underwent immediate postnatal reconstruction. METHODS: Between
      2000 and 2005, classic bladder exstrophy patients referred to the authors'
      institution underwent early neonatal bladder closure (group 1). Subsequently,
      classic bladder exstrophy patients referred to the authors' institution were
      treated with an elective DER (group 2). Bladder capacity was assessed between the
      age of 1 and 4 years with an unconscious cystogram. When dilating VUR was
      present, the volume of the contrast migrated into the ureter was calculated and
      subtracted. RESULTS: Sixty patients were treated between 2000 and 2012. Complete
      follow-up data were available for 45 patients and they were included in the
      study: 21 in group 1 (11 males) and 24 in group 2 (14 males). The mean (SD)
      bladder volumes were 72.85 (28.5) ml in group 1 and 72.87 (34.9) in group 2 (p =
      0.99). CONCLUSION: In the authors' experience, DER does not reduce the subsequent
      bladder capacities compared with neonatal exstrophy closure.

PMID- 24331167
TI  - Comparison between laparoscopic and open radical nephrectomy for the treatment of
      primary renal tumors in children: single-center experience over a 5-year period.
AB  - OBJECTIVES: To compare the outcomes of laparoscopic nephrectomy (LN) with open
      radical nephrectomy (ORN) in the management of consecutive pediatric neoplasms.
      PATIENTS AND METHODS: Retrospective cohort study of consecutive children treated
      for primary renal tumors between 2006 and 2011, segregated based on surgical
      modality (LN/ORN). Pre-, intra- and postoperative data and outcomes were
      collected. RESULTS: Demographics from the 45 patients (13 LN, 32 ORN) were
      similar, and tumors in the LN group were smaller [6.59 +/- 1.8 cm vs. 10.99 +/-
      2.99 cm ORN (p < 0.05)]. Six patients had preoperative chemotherapy (two LN, four
      ORN). No tumor ruptures occurred with either technique. Wilms tumor (seven LN, 24
      ORN) was the most common diagnosis, followed by renal cell carcinoma (four LN,
      four ORN). Procedure length was similar between groups (282 +/- 79 LN, 263 +/- 81
      min ORN). Mean length of stay was significantly shorter for LN (2.9 vs. 5.9 days;
      p = 0.002). Postoperative narcotic requirements and use of nasogastric tube were
      higher in the ORN group. After a median follow-up of 18 (LN) and 33 months (ORN),
      1 and 4 recurrences occurred, respectively. CONCLUSIONS: LN is an attractive
      alternative to open surgery in carefully selected cases of pediatric renal
      tumors. Procedure length and incidence of intra-operative rupture were not
      increased, while post-operative recovery and hospital stay were shorter for LN.
      Longer follow-up is mandatory to confirm comparable oncological outcomes to ORN.

PMID- 24331168
TI  - Association between insulin resistance, cardiovascular risk factors and
      overweight in Japanese schoolchildren.
AB  - SUMMARY:  OBJECTIVE: The aim of this study was to examine the association between
      insulin resistance, cardiovascular risk factors and overweight in Japanese
      schoolchildren. METHODS: A cross-sectional study was performed on 310
      schoolchildren (155 boys and 155 girls) of the fifth grade and the eighth grade
      in a town in Nagano Prefecture, Japan. The survey was conducted on
      anthropometric, blood examinations, and by calculation of body mass index (BMI:
      body weight/body height(2)) and HOMA-IR (fasting insulin * fasting glucose/405).
      RESULTS: Hemoglobin A1c and fasting glucose were not associated with BMI, whereas
      fasting insulin and HOMA-IR were significantly higher in overweight children in
      comparison with the lowest quartile BMI group. In the overweight, the mean and
      standard deviation of HOMA-IR were 2.51 +/- 1.01, and the prevalence of HOMA-IR ?
      2.5 was 46.8%. Schoolchildren with HOMA-IR ? 2.5 had more several cardiovascular
      risk factors. CONCLUSIONS: Insulin resistance was observed in overweight Japanese
      children, though their hemoglobin A1c and fasting glucose were within the normal
      range. In addition, with higher BMI, the number of cardiovascular risk factors
      was increased. Weight management should be started in childhood.

PMID- 24331169
TI  - Dysmetabolic signals in "metabolically healthy" obesity.
AB  - SUMMARY:  BACKGROUND: Obesity is associated with decreased insulin sensitivity,
      atherogenic dyslipidemia and hypertension, but clinical studies have also
      identified a "metabolically healthy" obese phenotype. OBJECTIVE: To compare the
      characteristics of so-called "metabolically healthy" obese (MHO), normal weight
      subjects (MHNW) and obese with insulin resistance in the United States National
      Health and Nutrition Examination Survey, 1999-2004 (NHANES). DESIGN, SETTING AND
      PARTICIPANTS: Insulin resistance was defined by a homeostatic model assessment
      (HOMA) value in the upper tertile for the entire NHANES cohort. "Metabolic
      health" was defined as the absence of diabetes, insulin resistance, metabolic
      syndrome, and lipid-lowering therapy. The study evaluated the 314 MHO, 1173 MHNW
      and 843 insulin-resistant obese from among the 6485 non-diabetic, non-pregnant
      adults aged 20-79 years. MAIN OUTCOME MEASURES: Demographic, metabolic, nutrition
      and physical activity features. RESULTS: MHO and MHNW groups were similar
      regarding age, and fasting glucose and triglyceride levels. MHO had higher
      insulin (P < 0.0001), insulin resistance as measured with the homeostatic model
      (P < 0.0001), non-HDL cholesterol (P = 0.002 in females and P = 0.049 in males)
      and C-reactive protein levels (P < 0.0001 in females and P = 0.038 in males), and
      lower high-density lipoprotein cholesterol (HDL) levels (P < 0.002). In addition,
      MHO females had higher low-density lipoprotein (LDL) cholesterol levels (P =
      0.012) and systolic blood pressure (P = 0.02), and lower intake of dietary fiber
      (P = 0.0009) and levels of physical activity (P = 0.002). Triglycerides levels
      were normal in the MHO group. CONCLUSIONS: "Metabolically healthy" obese people
      have multiple dysmetabolic changes that may signal increased risk for coronary
      artery disease.

PMID- 24331170
TI  - Acceptance and commitment therapy for bariatric surgery patients, a pilot RCT.
AB  - SUMMARY: Bariatric surgery (BS) is rated as the best evidence based treatment for
      obesity with regard to weight loss and maintenance of weight loss evaluated to
      date. Although BS interventions are effective, 20-30% of BS patients start to
      regain weight within 24 months. Emotional eating is a behavior pattern which has
      been found to predict poor outcome. The aim of this study is to evaluate the
      effects of acceptance and commitment therapy (ACT) for patients who underwent BS,
      with regard to emotional eating, body dissatisfaction and quality of life. This
      study is a randomized controlled trial (n = 39) with two conditions (1) ACT
      including two face-to-face sessions and support via an Internet application and
      (2) treatment as usual (TAU) comprising the standard follow-up used by the BS
      team. Results show that participants in the ACT condition significantly improve
      on eating disordered behaviors, body dissatisfaction, quality of life and
      acceptance for weight related thoughts and feelings, as compared to those in the
      TAU group. This study shows that it is possible to improve effects of BS by
      specifically targeting emotional eating behavior.:

PMID- 24331171
TI  - The risky body mass index ranges for significant hepatitis B viral load: A campus
      based study.
AB  - SUMMARY: Significant hepatitis B viral load (>=10,000 copies/mL) was established
      to increase risk of advanced liver diseases. The aim of this study was to explore
      the metabolic risk factors for significant hepatitis B viral load. A campus-based
      cohort consisting of 146 participants of chronic hepatitis B virus (HBV)
      infection in Northern Taiwan was investigated in 2009. Clinical profiles
      including serum levels of deoxyribonucleic acid of hepatitis B virus (HBV DNA)
      were collected. Hepatitis B e antigen (HBeAg) serostatus, high alanine
      aminotransferase level, body mass index (BMI) ranges, and insulin resistance were
      related to significant HBV DNA levels in univariate analysis. Compared to
      individuals with BMI 23-24.9 kg/m(2) in multivariate analysis, those with BMI
      >=25 kg/m(2) (OR = 3.86, 95% CI = 1.38-10.8, P = 0.010) and those with BMI <23
      kg/m(2) (OR = 4.47, 95% CI = 1.32-15.2, P = 0.016) were at higher risk for
      significant HBV DNA levels. This phenomenon was also manifest in HBeAg
      seronegatives, who contributed to a majority of significant viral load in our
      study. Furthermore, insulin resistance and BMI >=25 kg/m(2) had positive additive
      effects on significant HBV DNA levels (adjusted OR = 9.34, 95% CI = 1.74-50.3, P
      = 0.009). In conclusion, having certain BMI ranges (BMI >=25 kg/m(2) or BMI <23
      kg/m(2)) could be a risk factor of significant HBV DNA levels.:

PMID- 24331172
TI  - Do cell phones, iPods/MP3 players, siblings and friends matter? Predictors of
      child body mass in a U.S. Southern Border City Middle School.
AB  - SUMMARY:  OBJECTIVE: This study examines the association of children's (i) micro
      social environment, specifically siblings [kin-friends] and friends from school
      and neighborhood [non-kin-friends], and (ii) ownership of information and
      communication technologies (ICT), specifically cell phones and iPod/MP3 players,
      with body mass index percentile (BMIp). SUBJECTS: Fifty-five randomly selected
      6th graders with a mean age of 12 years, stratified by gender (23 boys and 32
      girls), from a Texas middle school located in a city along the U.S. southern
      border. METHODS: The linear regression of BMIp on number of siblings and of non
      kin-friends, and ownership of cell phone and of iPod/MP3 player was examined
      using two models: M1 was based on the manual selection of predictors from a pool
      of potential predictors. M2 was derived from the predictors specified in M1 using
      backward elimination technique. Because sample size was small, the significance
      of regression coefficients was evaluated using robust standard errors to
      calculate t-values. Data for predictors were obtained through a survey. Height
      and weight were obtained through actual anthropometric measurements. BMIp was
      calculated using the on-line BMI calculator of the Center for Disease Control and
      Prevention. RESULTS: Findings reveal that children's social environment and ICT
      ownership predict BMIp; specifically, number of siblings (M2: beta = -0.34, p
      value < .001), and ownership of iPod/MP3 players (M2: beta = 0.33, p-value <
      .001). These results underscore the importance of family in configuring, and of
      new personal technical devices (that encourage solitary, and oftentimes
      sedentary, activities) in predicting child body mass.

PMID- 24331173
TI  - Hepatic tumor necrosis factor-alpha, leptin and adiponectin expression in morbid
      obese patients: Clinicopathological correlations.
AB  - SUMMARY:  BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with
      obesity. We retrospectively studied the clinicopathology and different hepatic
      adipocytokine expressions between nonalcoholic steatohepatitis (NASH) and non
      NASH in morbid obesity. METHODS: We enrolled 40 patients undergoing liver biopsy
      during bariatric surgery. We analyzed hepatic mRNA and immunohistochemistry of
      TNF-alpha, leptin, adiponectin and adiponectin receptor. RESULTS: Thirty patients
      (75%) presented with NASH, including 11 with mild fibrosis and 19 with advanced
      fibrosis. The HbA1c (P = 0.000), AST (P = 0.000), ALT (P = 0.000), GGT (P =
      0.016) and liver fibrosis (P = 0.028) have statistically difference between NASH
      and non-NASH groups. Steatosis was the only significant factor (r = 0.348, P <
      0.05) associated with TNF-alpha mRNA level. Adiponectin mRNA was inversely
      associated with C-peptide (r = -0.416, P < 0.05) and uric acid level (r = -0.426,
      P < 0.05). The best predictors for TNF-alpha immunostain were hemoglobin (r =
      0.432, P < 0.01), AST (r = 0.371, P < 0.05), lobular inflammation (r = 0.315, P <
      0.05), portal inflammation (r = 0.331, P < 0.05), and NAS (r = 0.365, P < 0.05).
      Leptin immunostain was correlated with C-peptide (r = 0.356, P < 0.05) and portal
      inflammation (r = 0.334, P < 0.05). The AdipoRII immunoexpression was negatively
      correlated with systolic blood pressure (r = -0.481, P < 0.01). Multivariate
      linear regressions of adipocytokine profile related mostly to age, gender,
      systolic blood pressure, serum uric acid, steatosis, NAS and portal inflammation.
      CONCLUSION: Although different adipocytokines may be associated with NAFLD
      progression in morbid obesity, their major correlations in the pathogenesis of
      obesity-related NASH are not clear. Additional confirmatory studies are deserved.

PMID- 24331174
TI  - Ageing, adiposity indexes and low muscle mass in a clinical sample of overweight
      and obese women.
AB  - SUMMARY:  OBJECTIVE: Ageing is associated with a progressive decline in the
      quantity (mass) and quality (function) of the muscular tissue. To assess the
      prevalence of low muscle mass (LMM) alone and in combination with high adiposity
      (LMM-HA) in a clinical representative sample of adult women and to determine how
      the prevalence of (LMM-HA) changes using different adiposity indexes. METHODS:
      763 overweight and obese women (age range: 18-87 years) attending a weight loss
      clinic. Weight, height, and waist circumference (WC) were measured and BMI
      calculated. Bioelectrical impedance (BIA) was used to measure fat mass (FM).
      Skeletal muscle index (SMI) was used for the diagnosis of LMM. Adiposity indexes
      (BMI, WC, FM%, FM index) were combined with SMI to assess the prevalence of LMM
      HA. RESULTS: The prevalence of LMM was 27.4% in women older than 60 years.
      Established cut-off scores for excess adiposity determined differences in the
      prevalence of LMM-HA. The lowest was observed using the BMI derived cut-off score
      (>=30 kg/m(2)), with FM% (>=35%) the most inclusive, classifying more than 90% of
      sarcopenia cases as LMM-HA. CONCLUSIONS: The prevalence of LMM-HA is different
      between anthropometric (BMI, WC) and bioimpedance measures (FM% and FMI) of
      adiposity. The sensitivity of the adiposity indexes for the diagnosis of
      sarcopenic obesity and its impact on the prediction of cardio-metabolic diseases
      remain to be tested.

PMID- 24331175
TI  - A 12-week, randomised, controlled trial to examine the acceptability of the
      Korean diet and its effectiveness on weight and metabolic parameters in an
      Australian overweight and obese population.
AB  - SUMMARY:  BACKGROUND: South Korea has a significantly lower prevalence of
      overweight and obesity compared to Western countries. This may be due to
      differences between the traditional Korean diet (KD) and western diet (WD).
      OBJECTIVE: Our study investigated whether a Western population would accept a KD,
      compared to a WD, in a weight loss oriented lifestyle program. DESIGN: 70
      overweight or obese participants were randomised to a 12-week weight loss
      program. All participants followed a standardised lifestyle intervention
      incorporating diet, exercise and behavioural modification techniques. KD
      participants were provided with a traditional Korean lunch and dinner (Monday to
      Saturday). WD participants were provided with a weekly grocery food voucher.
      Weight and metabolic parameters were measured. RESULTS: 60 participants completed
      the study (KD = 25; WD = 35). No significant difference was found for percentage
      weight loss (KD: -5.8 +/- 4.7%; WD: -5.7 +/- 4.1%; p = 0.93). On the 10-item Food
      Acceptability Questionnaire, there was a decline in acceptance for the KD group
      over the 12-week intervention. CONCLUSIONS: When incorporated into a lifestyle
      intervention a traditional KD resulted in similar weight loss to a WD, despite a
      significantly higher energy intake. Food acceptability scores significantly
      favoured the WD for some of the measures at week 12, and the most common staple
      Korean foods were reported highest amongst the food returns, suggesting that the
      KD was not as well accepted and less enjoyable on a range of measures. More
      variability in the menu and flexibility in portion sizes of the KD may improve
      its acceptance and could further optimise its weight loss potential for
      Westerners.

PMID- 24331176
TI  - Quercetin/adenosine combination may induce insulin resistance in high fat diet
      fed mice.
AB  - SUMMARY: Quercetin and adenosine are natural antioxidants separately claimed to
      improve metabolic syndrome parameters. The effect of this combination (QA) was
      examined in high fat diet-fed mice. Results showed that growth and blood
      parameters, as observed for quercetin-treated mice, were not significantly
      different from the control. Adenosine alone caused hyperglycemia and reduced
      plasma adiponectin. QA feeding led to increased adiposity and circulatory
      insulin, and concomitantly down-regulated liver eNOS and LFABP expressions. This
      showed that interaction occurred between quercetin and adenosine, and combined
      ingestion may lead to insulin resistance, while adenosine does not prevent the
      development of metabolic syndrome.:

PMID- 24331177
TI  - Lessons for the Australian healthcare system from the Berwick report.
AB  - There are common key recommendations in the raft of recent reports from inquiries
      into hospital quality and safety issues, both in Australia and in the United
      Kingdom. Prime among these is that governments, bureaucrats, clinicians and
      administrators must work together to place the quality and safety of patient care
      above all other aims in the healthcare system. Performance targets and
      enforcement, although needed, are not the route to improvement; what is required
      is a change in culture to drive a system of care that is open to learning,
      capable of identifying and admitting its problems and acting to correct them, and
      where the patient's voice is always heard. 

PMID- 24331179
TI  - Management of pancreatic cancer.

PMID- 24331180
TI  - Irreversible electroporation: a novel pancreatic cancer therapy.

PMID- 24331181
TI  - Pain management and palliative care in pancreatic cancer.

PMID- 24331182
TI  - Current advances in immunotherapy for pancreatic cancer.

PMID- 24331184
TI  - Diabetes and pancreatic cancer.

PMID- 24331183
TI  - Stem cell-directed therapies in pancreatic cancer.

PMID- 24331185
TI  - The role of endoscopy in the treatment, management, and personalization of
      pancreatic cancer.

PMID- 24331187
TI  - Costs of cancer care: rhetoric, value, and steps forward.

PMID- 24331188
TI  - Introduction: The science of survivorship: moving from risk to risk reduction.

PMID- 24331186
TI  - Radiosensitizers in pancreatic cancer--preclinical and clinical exploits with
      molecularly targeted agents.

PMID- 24331189
TI  - Therapy-related myelodysplasia and acute myeloid leukemia.
AB  - Therapy-related leukemia (myelodysplasia and acute myeloid leukemia-t-MDS/AML) is
      a well-known complication of conventional chemoradiotherapy used to treat a
      variety of primary malignancies including Hodgkin lymphoma (HL) and non-Hodgkin
      lymphoma (NHL), acute lymphoblastic leukemia (ALL), sarcoma, and ovarian and
      testicular cancers. The median time to development of t-MDS/AML is 3-5 years,
      with the risk decreasing markedly after the first decade. t-MDS/AML is the major
      cause of non-relapse mortality after autologous hematopoietic cell
      transplantation (HCT) for HL or NHL. The magnitude of risk of t-MDS/AML is
      higher, and the latency is shorter after HCT, compared to conventional therapy.
      Two types of t-MDS/AML are recognized depending on the causative therapeutic
      exposure: an alkylating agent/radiation-related type and a topoisomerase II
      inhibitor-related type. Inter-individual variability in the risk for development
      of t-MDS/AML suggests a role for genetic variation in susceptibility to genotoxic
      exposures. Treatment of t-MDS/AML with conventional therapy is associated with a
      uniformly poor prognosis, with a median survival of 6 months. Because of the poor
      response to conventional chemotherapy, allogeneic HCT is recommended. Current
      research is focused on developing risk prediction and risk reduction strategies. 

PMID- 24331191
TI  - Cancer survivorship: cardiotoxic therapy in the adult cancer patient; cardiac
      outcomes with recommendations for patient management.
AB  - Many types of cancer are now curable or, if not cured, becoming a chronic
      illness. In 2012, it was estimated that there were more than 13,500,000 cancer
      survivors in the United States. Late outcomes of these survivors are increasingly
      related to cardiovascular disease, either as a consequence of the direct effects
      of cancer therapy or its adverse effects on traditional cardiac risk factors (eg,
      obesity, hypertension, dyslipidemia, and diabetes mellitus). This article
      describes the therapies that have led to advances in cancer survival and the
      acute and chronic cardiovascular toxicities associated with these therapies.
      Recommendations are made for the surveillance and management of cancer survivors.
      Published guidelines on the subject of cardio-oncology are reviewed in light of
      clinical experience caring for these patients. To supplement this cancer-related
      knowledge base, appropriateness criteria and guidelines for cardiac care in the
      general population were extrapolated to cancer survivors. The result is a series
      of recommendations for surveillance and management of cardiovascular disease in
      cancer survivors. 

PMID- 24331190
TI  - Solid tumor second primary neoplasms: who is at risk, what can we do?
AB  - Eighteen percent of incident malignancies in the United States are a second (or
      subsequent) cancer. Second primary neoplasms (SPNs), particularly solid tumors,
      are a major cause of mortality and serious morbidity among cancer survivors
      successfully cured of their first cancer. Multiple etiologies may lead to a
      cancer survivor subsequently being diagnosed with an SPN, including radiotherapy
      for the first cancer, unhealthy lifestyle behaviors, genetic factors, aging, or
      an interaction between any of these factors. In this article, we discuss these
      factors and synthesize this information for use in clinical practice, including
      preventive strategies and screening recommendations for SPNs. 

PMID- 24331193
TI  - Sexual and reproductive health in cancer survivors.
AB  - As patients live longer after cancer diagnosis and treatment, attention to
      symptoms and quality of life (QoL) are of increasing importance both during
      treatment and throughout survivorship. Two complications of multi-modal cancer
      treatment that can profoundly affect both men and women are sexual dysfunction
      and infertility. Survivors at highest risk for treatment-related sexual
      dysfunction are those with tumors that involve the sexual or pelvic organs and
      those whose treatment affects the hormonal systems mediating sexual function.
      Sexual dysfunction may not abate without appropriate intervention. Therefore,
      early identification and treatment strategies are essential. Likewise, multiple
      factors contribute to the risk of infertility from cancer treatment and many
      cancer patients of reproductive age would prefer to maintain their fertility, if
      possible. Fortunately, advances in reproductive technology have created options
      for young newly diagnosed patients to preserve their ability to have a biologic
      child. This paper will focus on the sexual and reproductive problems encountered
      by cancer survivors and discuss some treatment options. 

PMID- 24331195
TI  - Renal and pulmonary late effects of cancer therapy.
AB  - Both the kidneys and lungs are susceptible to the toxic effects of cancer
      therapy, with specific chemotherapy agents, as well as radiation therapy, leading
      to acute toxicities and the risk for long-term dysfunction. The kidneys also are
      vulnerable to the direct impact of the cancer itself and to supportive care drugs
      such as certain anti-infectives and immunosuppressive agents, nonsteroidal anti
      inflammatories, and radiocontrast media. The lungs are especially vulnerable
      after hematopoietic stem cell transplantation (HSCT), particularly in patients
      who develop chronic graft-versus-host disease. This article will discuss the
      epidemiology, specific risk factors, pathogenesis, natural history, recommended
      screening, preventive strategies, treatment, and areas for future research into
      renal and pulmonary toxicity in survivors of cancer. 

PMID- 24331196
TI  - Symptom management and psychosocial outcomes following cancer.
AB  - Transition from the completion of cancer treatment to post-treatment is a pivotal
      first step in survivorship. Following the end of treatment patients may
      experience lingering symptoms, compromised physical function, and emotional
      distress. Within the larger survivorship literature less attention has been
      devoted to this immediate post acute treatment period. To organize this review a
      post-treatment risk model is presented; it is informed by the emotional health
      and comorbid conditions patients bring to their treatment. When integrated with
      the aggressiveness of treatment(s), the side effects experienced, and emotional
      responses, this profile defines and characterizes patients' post-treatment needs.
      Some patients need little more than a standard survivorship care plan with
      clearly defined shared care responsibilities for the oncologist and primary care
      physician. Others need more and varied forms of assistance. This review documents
      the range of physical and psychosocial problems patients' face as they transition
      from active treatment to survivorship. We conclude with suggestions for future
      research tailored to patient's post-treatment needs for care. 

PMID- 24331192
TI  - Cognitive effects of cancer and its treatments at the intersection of aging: what
      do we know; what do we need to know?
AB  - There is a fairly consistent, albeit non-universal body of research documenting
      cognitive declines after cancer and its treatments. While few of these studies
      have included subjects aged 65 years and older, it is logical to expect that
      older patients are at risk of cognitive decline. Here, we use breast cancer as an
      exemplar disease for inquiry into the intersection of aging and cognitive effects
      of cancer and its therapies. There are a striking number of common underlying
      potential biological risks and pathways for the development of cancer, cancer
      related cognitive declines, and aging processes, including the development of a
      frail phenotype. Candidate shared pathways include changes in hormonal milieu,
      inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic
      susceptibility, decreased brain blood flow or disruption of the blood-brain
      barrier, direct neurotoxicity, decreased telomere length, and cell senescence.
      There also are similar structure and functional changes seen in brain imaging
      studies of cancer patients and those seen with "normal" aging and Alzheimer's
      disease. Disentangling the role of these overlapping processes is difficult since
      they require aged animal models and large samples of older human subjects. From
      what we do know, frailty and its low cognitive reserve seem to be a clinically
      useful marker of risk for cognitive decline after cancer and its treatments. This
      and other results from this review suggest the value of geriatric assessments to
      identify older patients at the highest risk of cognitive decline. Further
      research is needed to understand the interactions between aging, genetic
      predisposition, lifestyle factors, and frailty phenotypes to best identify the
      subgroups of older patients at greatest risk for decline and to develop
      behavioral and pharmacological interventions targeting this group. We recommend
      that basic science and population trials be developed specifically for older
      hosts with intermediate endpoints of relevance to this group, including cognitive
      function and trajectories of frailty. Clinicians and their older patients can
      advance the field by active encouragement of and participation in research
      designed to improve the care and outcomes of the growing population of older
      cancer patients. 

PMID- 24331194
TI  - Energy balance and metabolism after cancer treatment.
AB  - Unfavorable physiological, biological, and behavioral alterations during and
      following treatment for cancer may lead to chronic energy imbalance predisposing
      to a myriad of deleterious health conditions including obesity, dyslipidemia, and
      the metabolic syndrome. In addition to the cardiovascular and musculoskeletal
      effects of these conditions, energy imbalance and metabolic changes after cancer
      treatment can also affect cancer-related morbidity and mortality. To this end,
      lifestyle interventions such as diet and physical activity are especially
      relevant to mitigate the deleterious impact of chronic energy imbalance in cancer
      survivors. 

PMID- 24331197
TI  - Physical functioning and rehabilitation for the cancer survivor.
AB  - There are more than 13.8 million survivors of cancer living in the United States.
      Up to 20% of survivors of childhood-onset and 53% of survivors of adult-onset
      cancer have problems with physical function as a result of their cancer and or
      its treatment. These problems may be immediately apparent, during, or soon after
      initial cancer treatment, or may appear days, months, or years later as the
      cancer survivor ages. Unfortunately, rehabilitation services and providers are
      not easily or systematically accessible in today's healthcare system.
      Rehabilitation services that restore or ameliorate early functional loss or that
      protect against or minimize the impact of later-onset organ system dysfunction
      are available, at least in larger comprehensive cancer center settings. This
      report describes physical function, details the evolution of cancer
      rehabilitation, and identifies cancer survivors who may benefit from
      rehabilitation services. Additionally, the evidence for specific approaches to
      rehabilitation, intervention, and prevention of functional loss are reviewed.
      Finally, we summarize the mechanisms used to measure physical function and stress
      the need for additional research to support rehabilitation services for cancer
      survivors. 

PMID- 24331198
TI  - Health disparities and the cancer survivor.
AB  - Disparities on the basis of race and ethnicity have been described in a variety
      of survivorship outcomes, including late and long-term effects of treatment,
      surveillance and health maintenance, and psychosocial outcomes. However, the
      current body of literature is limited in scope and additional research is needed
      to better define and address disparities among cancer survivors. 

PMID- 24331200
TI  - A roundtable discussion on the clinical challenges and options for the treatment
      of glioblastoma: introducing a novel modality, TTFields.
AB  - Since its approval in 2011 for patients with recurrent glioblastoma (GBM),
      physicians have responded positively to the non-invasive nature of the NovoTTF
      100A System device (NovoCure Ltd, Haifa, Israel), citing significantly less
      toxicity and a better quality of life profile compared to available conventional
      therapies. A roundtable discussion (available at:
      http://education.seminoncol.org/path.php?1399:0:Media:title:bxvcs) was recently
      convened to provide a knowledge-based perspective surrounding current treatment
      options for patients with GBM and the clinical challenges involved with the
      treatment of recurrent GBM patients who have failed prior therapies. The
      participating roundtable experts discussed the challenges encountered in managing
      GBM patients, the current approved treatment options for these patients, the
      efficacy and safety profile of NovoTTF therapy (TTFields), and its use as a novel
      treatment modality for recurrent GBM patients. 

PMID- 24331199
TI  - Risk-based health care, the cancer survivor, the oncologist, and the primary care
      physician.
AB  - Cancer survivors face substantial risks for morbidity, reduced quality of life,
      and premature mortality related to the cancer itself and/or the interventions
      undertaken to control cancer. Risk-based care that involves a personalized
      systematic plan of periodic screening, surveillance, and prevention relevant to
      the cancer experience is recommended to address the comprehensive health needs of
      the growing population of cancer survivors. Risk-based care and coordination
      between oncology and primary care providers have been identified as important
      metrics of quality cancer survivorship care. Various models of survivorship care,
      treatment summaries, and survivorship care plans have been promoted as methods to
      facilitate communication among providers across care transitions and improve
      survivor access to quality survivorship care. However, research supporting the
      feasibility of implementing these practices and their effectiveness in enhancing
      health outcomes is limited. This article reviews key concepts underpinning
      clinical and research initiatives endeavoring to improve access to quality care
      among long-term survivors and summarizes results of intervention studies
      implementing these elements in transitioning survivors from oncology to primary
      care providers for long-term follow-up care. 

PMID- 24331201
TI  - Dietary phyto-oestrogens and the risk of ovarian and endometrial cancers:
      findings from two Australian case-control studies.
AB  - Phyto-oestrogens have been suggested to have a protective effect on hormone
      sensitive cancers. However, few studies have investigated the association between
      dietary phyto-oestrogens and gynaecological cancers. In the present study, we
      analysed data from two population-based case-control studies of ovarian (1366
      cases and 1414 controls) and endometrial (1288 cases and 1435 controls) cancers.
      Dietary intake information was obtained using a 135-item FFQ, and phyto-oestrogen
      intake was estimated using published food composition databases. Unconditional
      logistic regression was used to estimate adjusted OR and 95% CI. In multivariable
      analyses, there was a suggestive pattern of inverse associations between
      increasing intakes of total phyto-oestrogens, isoflavones and enterolignans and
      the risk of ovarian cancer. However, the results only reached statistical
      significance for the lignan compounds matairesinol and lariciresinol, where the
      OR for the highest v. the lowest intake category was 0.72 (95% CI 0.54, 0.96; P
      for trend = 0.02) for matairesinol and 0.72 (95% CI 0.55, 0.96; P for trend =
      0.03) for lariciresinol. When the risk of ovarian cancer was assessed by subtype,
      there was an indication that increasing intakes of phyto-oestrogens may be
      associated with a decreased risk of mucinous (cases n 158) ovarian tumours (OR
      for the highest v. the lowest intake category: 0.47 (95% CI 0.24, 0.93); P for
      trend = 0.04). However, there were no significant associations with other
      histological subtypes. In contrast, dietary phyto-oestrogens (total or any
      subclass) were unrelated to the risk of endometrial cancer cases overall or by
      subtype.

PMID- 24331202
TI  - Impairment of subendocardial perfusion reserve and oxidative metabolism in
      nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Cardiac magnetic resonance (CMR) and [(11)C]acetate positron emission
      tomography (PET) were used to assess the hypothesis that patients with
      nonischemic dilated cardiomyopathy (NIDCM) have decreased subendocardial
      perfusion reserve and impaired oxidative metabolism, consistent with the concept
      of "energy starvation" in heart failure (HF). METHODS AND RESULTS: CMR myocardial
      perfusion was evaluated in 13 NIDCM patients and 15 control subjects with
      coronary risk factors and normal myocardial perfusion. The NIDCM patients
      underwent [(11)C]acetate PET. The myocardial perfusion index (MPI) was calculated
      as the normalized rate of myocardial signal augmentation following gadolinium
      contrast injection. Hyperemic transmural, subendocardial, and subepicardial MPI
      were reduced in NIDCM compared with control subjects [0.13 vs 0.18 (P < .001),
      0.13 vs 0.17 (P < .001), and 0.13 vs 0.17 (P = .008), respectively]. The
      subendocardial perfusion reserve was 1.59 +/- 0.21 vs 1.86 +/- 0.32 for the
      subepicardium (P = .002), demonstrating reduced perfusion reserve. The myocardial
      oxidative metabolic rate (kmono) per unit demand (rate-pressure product) was
      reduced in proportion to perfusion reserve (P = .02) CONCLUSIONS: Impaired
      subendocardial perfusion reserve in NIDCM confirmed results previously attained
      only in animal models. Impaired perfusion and impaired oxidative metabolism are
      consistent with subendocardial energy starvation in HF.

PMID- 24331205
TI  - Assessment of regional MR diffusion changes in dementia with Lewy bodies and
      Alzheimer's disease.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are
      common forms of dementia, yet diagnosis is often difficult. Diffusion tensor
      imaging (DTI) is an MR technique used to assess neuronal microstructural
      integrity that may help develop a better understanding of the differences between
      the conditions. METHODS: We recruited subjects with DLB (n = 35), AD (n = 36),
      and similar aged healthy controls (n = 35). T1 weighted anatomical and diffusion
      MR images were acquired at 3 Tesla. Region of interest (ROI) analysis was used to
      measure fractional anisotropy (FA) and mean diffusivity (MD) in five structures:
      precuneus, thalamus, pons, midbrain, and amygdala. Where appropriate diffusivity
      measures (FA, MD) were correlated with selected clinical measures. RESULTS:
      Compared to controls, DLB subjects were characterized by reduced FA (p = 0.016)
      and increased MD (p = 0.007) in the precuneus. Amygdala diffusivity was
      positively correlated with UPDRS-III score in DLB (p = 0.003). In AD, reduced FA
      in the precuneus was also observed compared to controls (p = 0.026), and was
      associated with impaired global cognition (MMSE score) (p = 0.03). CONCLUSIONS:
      Our findings highlight the potential importance of the precuneus in the
      pathogenesis of DLB as well as AD. Diffusion tensor MRI may shed new light on the
      different neurobiological changes underpinning the key clinical features of DLB
      and AD.

PMID- 24331206
TI  - Learnings from over 25 years of PNH experience: the era of targeted complement
      inhibition.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is a progressive and life-threatening
      disease that causes thrombosis, end organ damage and impaired quality of life.
      Chronic uncontrolled complement activation leads to chronic haemolysis, causing
      progressive morbidities and early mortality. Hence, early diagnosis is essential
      for improved patient management and prognosis. Eculizumab (SOLIRIS(r))
      specifically inhibits chronic, uncontrolled complement activation and is the
      first-in-class, humanised, monoclonal antibody targeting C5 within the terminal
      complement pathway. Eculizumab is the first and only approved treatment for PNH
      in adults and children. 

PMID- 24331204
TI  - Utilization of trained volunteers decreases 30-day readmissions for heart
      failure.
AB  - BACKGROUND: This study evaluated the effectiveness of using trained volunteer
      staff in reducing 30-day readmissions of congestive heart failure (CHF) patients.
      METHODS: From June 2010 to December 2010, 137 patients (mean age 73 years)
      hospitalized for CHF were randomly assigned to either: an interventional arm (arm
      A) receiving dietary and pharmacologic education by a trained volunteer, follow
      up telephone calls within 48 hours, and a month of weekly calls; or a control arm
      (arm B) receiving standard care. Primary outcomes were 30-day readmission rates
      for CHF and worsening New York Heart Association (NYHA) functional
      classification; composite and all-cause mortality were secondary outcomes.
      RESULTS: Arm A patients had decreased 30-day readmissions (7% vs 19%; P < .05)
      with a relative risk reduction (RRR) of 63% and an absolute risk reduction (ARR)
      of 12%. The composite outcome of 30-day readmission, worsening NYHA functional
      class, and death was decreased in the arm A (24% vs 49%; P < .05; RRR 51%, ARR
      25%). Standard-care treatment and hypertension, age >=65 years and hypertension,
      and cigarette smoking were predictors of increased risk for readmissions,
      worsening NYHA functional class, and all-cause mortality, respectively, in the
      multivariable analysis. CONCLUSIONS: Utilizing trained volunteer staff to improve
      patient education and engagement might be an efficient and low-cost intervention
      to reduce CHF readmissions.

PMID- 24331203
TI  - A trial of family partnership and education interventions in heart failure.
AB  - BACKGROUND: Lowering dietary sodium and adhering to medication regimens are
      difficult for persons with heart failure (HF). Because these behaviors often
      occur within the family context, this study evaluated the effects of family
      education and partnership interventions on dietary sodium (Na) intake and
      medication adherence (MA). METHODS AND RESULTS: HF patient and family member (FM)
      dyads (n = 117) were randomized to: usual care (UC), patient-FM education (PFE),
      or family partnership intervention (FPI). Dietary Na (3-day food record), urinary
      Na (24-hour urine), and MA (Medication Events Monitoring System) were measured at
      baseline (BL) before randomization, and at 4 and 8 months. FPI and PFE reduced
      urinary Na at 4 months, and FPI differed from UC at 8 months (P = .016). Dietary
      Na decreased from BL to 4 months, with both PFE (P = .04) and FPI (P = .018)
      lower than UC. The proportion of subjects adherent to Na intake (<=2,500 mg/d)
      was higher at 8 months in PFE and FPI than in UC (chi(2)(2) = 7.076; P = .029).
      MA did not differ among groups across time. Both FPI and PFE groups increased HF
      knowledge immediately after intervention. CONCLUSIONS: Dietary Na intake, but not
      MA, was improved by PFE and FPI compared with UC. The UC group was less likely to
      be adherent with dietary Na. Greater efforts to study and incorporate family
      focused education and support interventions into HF care are warranted.

PMID- 24331207
TI  - Regulation of platelet responses triggered by Toll-like receptor 2 and 4 ligands
      is another non-genomic role of nuclear factor-kappaB.
AB  - INTRODUCTION: Platelets express Toll-like receptors (TLRs) that recognise
      molecular components of pathogens and, in nucleated cells, elicit immune
      responses through nuclear factor-kappaB (NF-kappaB) activation. We have shown
      that NF-kappaB mediates platelet activation in response to classical agonists,
      suggesting that this transcription factor exerts non-genomic functions in
      platelets. The aim of this study was to determine whether NF-kappaB activation is
      a downstream signal involved in TLR2 and 4-mediated platelet responses. MATERIAL
      AND METHODS: Aggregation and ATP release were measured with a Lumi-aggregometer.
      Fibrinogen binding, P-selectin and CD40 ligand (CD40L) levels and platelet
      neutrophil aggregates were measured by cytometry. I kappa B alpha (IkappaBalpha)
      degradation and p65 phosphorylation were determined by Western blot and von
      Willebrand factor (vWF) by ELISA. RESULTS: Platelet stimulation with Pam3CSK4 or
      LPS resulted in IkappaBalpha degradation and p65 phosphorylation. These responses
      were suppressed by TLR2 and 4 blocking and synergised by thrombin. Aggregation,
      fibrinogen binding and ATP and vWF release were triggered by Pam3CSK4. LPS did
      not induce platelet responses per se, except for vWF release, but it did
      potentiate thrombin-induced aggregation, fibrinogen binding and ATP secretion.
      Pam3CSK4, but not LPS, induced P-selectin and CD40L expression and mixed
      aggregate formation. All of these responses, except for CD40L expression, were
      inhibited in platelets treated with the NF-kappaB inhibitors BAY 11-7082 or Ro
      106-9920. CONCLUSION: TLR2 and 4 agonists trigger platelet activation responses
      through NF-kappaB. These data show another non-genomic function of NF-kappaB in
      platelets and highlight this molecule as a potential target to prevent platelet
      activation in inflammatory or infectious diseases.

PMID- 24331208
TI  - Usefulness of the INNOVANCE PFA P2Y test cartridge for the detection of patients
      with congenital defects of the platelet P2Y12 receptor for adenosine diphosphate.
AB  - INTRODUCTION: The platelet function analyzer (PFA)-100 is used in clinical
      practice to screen patients with bleeding diathesis and suspected defects of
      primary hemostasis. A new cartridge, INNOVANCE PFA P2Y, has been specifically
      developed to monitor patients' response to drugs inhibiting the platelet P2Y12
      receptor for ADP. In this study, we compared the ability of INNOVANCE PFA P2Y to
      detect congenital defects of the platelet P2Y12 receptor to that of standard
      cartridge formulations currently in clinical use. MATERIALS AND METHODS: We
      studied two patients with severe P2Y12 deficiency, one patient with heterozygous
      P2Y12 deficiency and one with dysfunctional P2Y12 receptor. Closure times were
      measured using 3 cartridges: collagen/ADP, collagen/epinephrine, and INNOVANCE
      PFA P2Y. The results obtained in the four patients with P2Y12 defects were
      compared to those obtained for 20 healthy controls. RESULTS: In 2 patients with
      severe P2Y12 deficiency, closure times of INNOVANCE PFA P2Y and collagen/ADP
      cartridges were >300 s, while those of collagen/epinephrine cartridge were
      variable (186s and >300 s). In the patient with dysfunctional P2Y12, closure time
      of INNOVANCE PFA P2Y was >300 s, while closure times of collagen/ADP and
      collagen/epinephrine were normal. Closure times of all cartridges were normal in
      the patient with heterozygous P2Y12 deficiency. CONCLUSION: Our study provides
      the first evidence that INNOVANCE PFA P2Y cartridge is sensitive to congenital
      severe and moderate defects of the platelet P2Y12 receptors.

PMID- 24331210
TI  - Self-testing of the International Normalized Ratio in adults with a mechanical
      heart valve: patient education and cost matter.

PMID- 24331209
TI  - High prevalence of recurrent thrombosis in subsets of cancer patients with
      isolated gonadal vein thrombosis: a single center retrospective study.
AB  - PURPOSE: Cancer patients are a high-risk population for venous thromboembolism
      (VTE); the natural history of gonadal vein thrombosis (GVT) occurring in cancer
      patients is not well described in the medical literature. METHODS: Utilizing a
      software program the computerized tomographic scan reports of patients at a
      single cancer center from January 1, 2004 to June 30, 2011 were searched for the
      term GVT. Patients included in this analysis had a diagnosis of cancer, an
      isolated GVT (i.e. no evidence of thrombosis at another site), no symptoms
      referable to the GVT, and at least six months of follow-up information. All
      subsequent recurrent VTE events were confirmed by imaging studies. RESULTS: 196
      cancer patients with GVT were identified. The majority of patients in this
      analysis had metastatic disease (118, 61.2%) as well as active cancer (167,
      85.2%). Twenty patients (10.8%) developed recurrent VTE (median follow-up 14.5
      months); median time to recurrent VTEs was 5.5 months (range 0-19 months). When
      considering only patients with without a recent history of gynecologic surgery,
      VTE recurrence rates were 14.3%. Active cancer was the only risk factor
      significantly associated with recurrent VTE (P=0.047). CONCLUSIONS: Based upon
      the patient's risk factors for VTE, treatment of an incidentally detected GVT in
      cancer patients with anticoagulation, as per guidelines for other VTE sites, may
      be indicated in certain high risk subgroups, especially those patients with
      active cancer who have not had prior pelvic surgery.

PMID- 24331212
TI  - Malaria and quinine resistance: a medical and scientific issue between Brazil and
      Germany (1907-19).
AB  - This article addresses the discussion about quinine-resistant malaria plasmodium
      in the early decades of the twentieth century. Observed by Arthur Neiva in Rio de
      Janeiro in 1907, the biological and social resistance of malaria sufferers to
      preventive and curative treatment with quinine was corroborated three years later
      by Oswaldo Cruz during the construction of the Madeira-Mamore Railway in the
      Brazilian Amazon. Likewise in 1910, ailing German workers were transferred from
      Brazil to Hamburg's Institute for Maritime and Tropical Diseases, where quinine
      resistance was confirmed by Bernard Nocht and Heinrich Werner. When the First
      World War saw failures in treating and preventing malaria with quinine along with
      violent outbreaks of the disease on the Turkish and Balkan fronts, resistance to
      this alkaloid became the topic of the day within the field of experimental
      medicine in Germany. New attempts were made to account for the resistance,
      especially by the physician Ernst Rodenwaldt, who explored the topic by applying
      modern theories on heredity. The present article offers a preliminary survey and
      analysis of pronouncements about quinine resistance, shedding new light on the
      circulation of knowledge in the field of tropical medicine. 

PMID- 24331211
TI  - Anti-human protein S antibody induces tissue factor expression through a direct
      interaction with platelet phosphofructokinase.
AB  - INTRODUCTION: Autoantibodies including anti-human protein S antibody (anti-hPS
      Ab) and anti-human protein C antibody (anti-hPC Ab) can be detected in patients
      with autoimmune diseases with hypercoagulability. The objective of the present
      study was to determine the effects and molecular pathways of these autoantibodies
      on tissue factor (TF) expression in human coronary artery endothelial cells
      (HCAECs). MATERIALS AND METHODS: HCAECs were treated with anti-hPS Ab or anti-hPC
      Ab for 3 hours. TF expression was measured by real-time PCR and Western blot. TF
      mediated procoagulant activity was determined by a commercial kit. MAPK
      phosphorylation was analyzed by Bio-Plex luminex immunoassay and Western blot.
      The potential proteins interacting with anti-hPS Ab were studied by
      immunoprecipitation, mass spectrometry and in vitro pull-down assay. RESULTS:
      Anti-hPS Ab, but not anti-hPC Ab, specifically induced TF expression and TF
      mediated procoagulant activity in HCAECs in a concentration-dependent manner.
      This effect was confirmed in human umbilical endothelial cells (HUVECs). ERK1/2
      phosphorylation was induced by anti-hPS Ab treatment, while inhibition of ERK1/2
      by U0216 partially blocked anti-hPS Ab-induced TF upregulation (P<0.05). In
      addition, anti-hPS Ab specifically cross-interacted with platelet
      phosphofructokinase (PFKP) in HCAECs. Anti-hPS Ab was able to directly inhibit
      PFKP activities in HCAECs. Furthermore, silencing of PFKP by PFKP shRNA resulted
      in TF upregulation in HCAECs, while activation of PFKP by fructose-6-phosphate
      partially blocked the effect of anti-hPS Ab on TF upregulation (P<0.05).
      CONCLUSIONS: Anti-hPS Ab induces TF expression through a direct interaction with
      PFKP and ERK1/2 activation in HCAECs. Anti-hPS Ab may directly contribute to
      vascular thrombosis in the patient with autoimmune disorders.

PMID- 24331213
TI  - Typhoid Fever in nineteenth-century Colombia: between medical geography and
      bacteriology.
AB  - This paper analyses how the Colombian medical elites made sense of typhoid fever
      before and during the inception of bacteriological ideas and practices in the
      second half of the nineteenth century. Assuming that the identity of typhoid
      fever has to be understood within the broader concerns of the medical community
      in question, I show how doctors first identified Bogota's epidemics as typhoid
      fever during the 1850s, and how they also attached specificity to the fever
      amongst other continuous fevers, such as its European and North American
      counterparts. I also found that, in contrast with the discussions amongst their
      colleagues from other countries, debates about typhoid fever in 1860-70 among
      doctors in Colombia were framed within the medico-geographical scheme and
      strongly shaped by the fear of typhoid fever appearing alongside 'paludic' fevers
      in the highlands. By arguing in medico-geographical and clinical terms that
      typhoid fever had specificity in Colombia, and by denying the medico-geographical
      law of antagonism between typhoid and paludic fevers proposed by the Frenchman
      Charles Boudin, Colombian doctors managed to question European knowledge and
      claimed that typhoid fever had distinct features in Colombia. The focus on
      paludic and typhoid fevers in the highlands might explain why the bacteriological
      aetiology of typhoid fever was ignored and even contested during the 1880s. Anti
      Pasteurian arguments were raised against its germ identity and some physicians
      even supported the idea of spontaneous origin of the disease. By the 1890s,
      Pasteurian knowledge had come to shape clinical and hygienic practices. 

PMID- 24331214
TI  - 'These schemes will win for themselves the confidence of the people': irish
      independence, poor law reform and hospital provision.
AB  - This article examines hospital provision in Ireland during the early twentieth
      century. It examines attempts by the newly independent Irish Free State to reform
      and de-stigmatise medical relief in former workhouse infirmaries. Such reforms
      were designed to move away from nineteenth century welfare regimes which were
      underpinned by principles of deterrence. The reform initiated in independent
      Ireland - the first attempted break-up of the New Poor Law in Great Britain or
      Ireland - was partly successful. Many of the newly named County and District
      Hospitals provided solely for medical cases and managed to dissociate such health
      care provision from the relief of poverty. However, some hospitals continued to
      act as multifunctional institutions and provided for various categories including
      the sick, the aged and infirm, 'unmarried mothers' and 'harmless lunatics'. Such
      institutions often remained associated with the relief of poverty. This article
      also examines patient fee-payment and outlines how fresh terms of entitlement and
      means-testing were established. Such developments were even more pronounced in
      voluntary hospitals where the majority of patients made a financial contribution
      to their treatment. The article argues that the ability to pay at times
      determined the type of provision, either voluntary or rate-aided, available to
      the sick. However, it concludes that the clinical condition of patients often
      determined whether they entered a more prestigious voluntary hospital or the
      former workhouse. Although this article concentrates on two Irish case studies,
      County Kerry and Cork City; it is conceptualised within wider developments with
      particular reference to the British context. 

PMID- 24331215
TI  - Medical officers, bodies, gender and weight fluctuation in irish convict prisons,
      1877-95.
AB  - This article focuses on the function of the convict prison infirmary and views it
      as a site of arbitration, resistance and 'contested power'. In accordance with
      the rules and regulations periods of incarceration in convict prisons began and
      ended with an obligatory medical examination. While the primary function of the
      initial test was to measure the convict body in order ascertain physical ability
      to conduct hard labour it also provided a thorough bio-metrical description for
      future identification purposes. The final examination was not as comprehensively
      undertaken but also concerned itself with anthropometrical observations. It would
      be reasonable to assume that the balance of power was weighted in the authority's
      favour but this research has found evidence to the contrary. For instance, that
      there was a fair degree of physiological knowledge within the convict population
      and that some convicts used the infirmary for dietary gains and reprieve from
      hard labour. Using body mass index (BMI) as an instrument to measure physical
      wellbeing this article views the doctor-convict interface as a crucial component
      of the penal experience. It analyses 251 convict medical records to show that the
      balance of diet and work led to what might be considered a counterintuitive
      outcome - a preponderance of weight gain, particularly for males in Irish
      prisons. 

PMID- 24331216
TI  - (Un)healthy relationships: African labourers, profits and health services in
      Angola's colonial-era diamond mines, 1917-75.
AB  - The Companhia de Diamantes de Angola, or Diamang, mined for diamonds in colonial
      Angola from 1917 until independence in 1975. The enterprise's Health Services
      Division (SSD) was responsible for supplying mine managers with an African labour
      force comprised of healthy, and therefore productive, employees. In practice,
      though, this otherwise 'healthy' system did not always work. While SSD personnel
      attempted to fulfil their charge by implementing a series of screening measures,
      production targets and a scarcely-populated regional labour pool regularly
      prompted senior officials to compel the SSD to clear recruits who were otherwise
      unfit for mine service. Drawing upon interviews with former SSD staff and African
      labourers, as well as company and colonial archival sources, this article focuses
      on the interplay over time between the SSD, the company's production demands and
      these labourers. 

PMID- 24331217
TI  - Recapturing the history of surgical practice through simulation-based re
      enactment.
AB  - This paper introduces simulation-based re-enactment (SBR) as a novel method of
      documenting and studying the recent history of surgical practice. SBR aims to
      capture ways of surgical working that remain within living memory but have been
      superseded due to technical advances and changes in working patterns. Inspired by
      broader efforts in historical re-enactment and the use of simulation within
      surgical education, SBR seeks to overcome some of the weaknesses associated with
      text-based, surgeon-centred approaches to the history of surgery. The paper
      describes how we applied SBR to a previously common operation that is now rarely
      performed due to the introduction of keyhole surgery: open cholecystectomy or
      removal of the gall bladder. Key aspects of a 1980s operating theatre were
      recreated, and retired surgical teams (comprising surgeon, anaesthetist and
      theatre nurse) invited to re-enact, and educate surgical trainees in this
      procedure. Video recording, supplemented by pre- and post-re-enactment
      interviews, enabled the teams' conduct of this operation to be placed on the
      historical record. These recordings were then used to derive insights into the
      social and technical nature of surgical expertise, its distribution throughout
      the surgical team, and the members' tacit and frequently sub-conscious ways of
      working. While acknowledging some of the limitations of SBR, we argue that its
      utility to historians - as well as surgeons - merits its more extensive
      application. 

PMID- 24331230
TI  - Delays in access to affordable medicines: putting policy into perspective -
      authors' response.

PMID- 24331231
TI  - Measures of muscular strength in U.S. children and adolescents, 2012.
AB  - KEY FINDINGS: Data from the National Health and Nutrition Examination Survey,
      National Youth Fitness Survey. There were no significant differences by sex in
      core, lower, or upper body measures of strength for younger boys and girls. In
      contrast, adolescent boys had higher values than adolescent girls on all measures
      of strength. Adolescent boys and girls had higher scores than younger boys and
      girls on the core and lower body strength measures and upper body strength as
      measured by the grip strength test. Adolescent boys completed more modified pull
      ups, a measure of upper body strength, than younger boys. There was no
      significant difference in the number of modified pull-ups completed between
      adolescent and younger girls. In 2008, the federal government released the
      Physical Activity Guidelines for Americans, which provide guidance on the types
      and amounts of physical activities that provide substantial health benefits for
      Americans of all ages. Regular physical activity reduces the risk of many adverse
      health outcomes and helps control the percentage of body fat in children and
      adolescents (1). This report provides the first nationally representative data on
      core, upper body, and lower body measures of muscle strength among U.S. children
      and adolescents aged 6-15 years by sex and age group.

PMID- 24331232
TI  - Classification of gender-based genitourinary and rectovaginal trauma in girls
      under 5years of age.

PMID- 24331233
TI  - On artefact-free reconstruction of low-energy (30-250eV) electron holograms.
AB  - Low-energy electrons (30-250eV) have been successfully employed for imaging
      individual biomolecules. The most simple and elegant design of a low-energy
      electron microscope for imaging biomolecules is a lensless setup that operates in
      the holographic mode. In this work we address the problem associated with the
      reconstruction from the recorded holograms. We discuss the twin image problem
      intrinsic to inline holography and the problem of the so-called biprism-like
      effect specific to low-energy electrons. We demonstrate how the presence of the
      biprism-like effect can be efficiently identified and circumvented. The presented
      sideband filtering reconstruction method eliminates the twin image and allows for
      reconstruction despite the biprism-like effect, which we demonstrate on both,
      simulated and experimental examples. 

PMID- 24331234
TI  - Staff attitudes towards sexual relationships among institutionalized people with
      dementia: does an extreme cautionary stance predominate?
AB  - BACKGROUND: This study explores whether staff perceptions and reactions to sexual
      situations involving one or two persons with dementia (PWD) reflect an extreme
      cautionary stance (an overprotective and paternalist style) or a person-centered
      model of care (focusing on understanding the residents' perspective and their
      rights). METHOD: Fifty-three staff members currently working in residential aged
      care facilities (RACFs) were purposively selected to participate in the study.
      Two vignettes describing sexual situations involving PWD were presented to
      participants. They were asked about their interpretation of the situation and how
      they would react. Data were analyzed using content analysis, aimed at identifying
      common themes in the responses. RESULTS: When the sexual relationship involved a
      PWD and a cognitively intact resident, participants tended to define the
      situation as real (54.7%) or possible (35.8%) abuse, whereas when both parties
      had dementia it was more frequently conceptualized as a possibly abusive (39.6%)
      or non-abusive (37.7%) situation. The most frequent reaction to both situations
      was seeking the advice of other professionals. CONCLUSION: The interpretation of
      the first situation is compatible with an extreme cautionary stance, whereas the
      second scenario is less clearly perceived as an example of abuse.

PMID- 24331235
TI  - Diabetes in the young - a global view and worldwide estimates of numbers of
      children with type 1 diabetes.
AB  - This paper describes the methodology, results and limitations of the 2013
      International Diabetes Federation (IDF) Atlas (6th edition) estimates of the
      worldwide numbers of prevalent cases of type 1 diabetes in children (<15 years).
      The majority of relevant information in the published literature is in the form
      of incidence rates derived from registers of newly diagnosed cases. Studies were
      graded on quality criteria and, if no information was available in the published
      literature, extrapolation was used to assign a country the rate from an adjacent
      country with similar characteristics. Prevalence rates were then derived from
      these incidence rates and applied to United Nations 2012 Revision population
      estimates for 2013 for each country to obtain estimates of the number of
      prevalent cases. Data availability was highest for the countries in Europe (76%)
      and lowest for the countries in sub-Saharan Africa (8%). The prevalence estimates
      indicate that there are almost 500,000 children aged under 15 years with type 1
      diabetes worldwide, the largest numbers being in Europe (129,000) and North
      America (108,700). Countries with the highest estimated numbers of new cases
      annually were the United States (13,000), India (10,900) and Brazil (5000).
      Compared with the prevalence estimates made in previous editions of the IDF
      Diabetes Atlas, the numbers have increased in most of the IDF Regions, often
      reflecting the incidence rate increases that have been well-documented in many
      countries. Monogenic diabetes is increasingly being recognised among those with
      clinical features of type 1 or type 2 diabetes as genetic studies become
      available, but population-based data on incidence and prevalence show wide
      variation due to lack of standardisation in the studies. Similarly, studies on
      type 2 diabetes in childhood suggest increased incidence and prevalence in many
      countries, especially in Indigenous peoples and ethnic minorities, but detailed
      population-based studies remain limited. 

PMID- 24331236
TI  - Isolation of a solventogenic Clostridium sp. strain: fermentation of glycerol to
      n-butanol, analysis of the bcs operon region and its potential regulatory
      elements.
AB  - A new solventogenic bacterium, strain GT6, was isolated from standing water
      sediment. 16S-rRNA gene analysis revealed that GT6 belongs to the heterogeneous
      Clostridium tetanomorphum group of bacteria exhibiting 99% sequence identity with
      C. tetanomorphum 4474(T). GT6 can utilize a wide range of carbohydrate substrates
      including glucose, fructose, maltose, xylose and glycerol to produce mainly n
      butanol without any acetone. Additional products of GT6 metabolism were ethanol,
      butyric acid, acetic acid, and trace amounts of 1,3-propanediol. Medium and
      substrate composition, and culture conditions such as pH and temperature
      influenced product formation. The major fermentation product from glycerol was n
      butanol with a final concentration of up to 11.5 g/L. 3% (v/v) glycerol lead to a
      total solvent concentration of 14 g/L within 72 h. Growth was not inhibited by
      glycerol concentrations as high as 15% (v/v). The solventogenesis genes crt, bcd,
      etfA/B and hbd composing the bcs (butyryl-CoA synthesis) operon of C.
      tetanomorphum GT6 were sequenced. They occur in a genomic arrangement identical
      to those in other solventogenic clostridia. Furthermore, the sequence of a
      potential regulator gene highly similar to that of the NADH-sensing Rex family of
      regulatory genes was found upstream of the bcs operon. Potential binding sites
      for Rex have been identified in the promoter region of the bcs operon of solvent
      producing clostridia as well as upstream of other genes involved in NADH
      oxidation. This indicates a fundamental role of Rex in the regulation of
      fermentation products in anaerobic, and especially in solventogenic bacteria.

PMID- 24331237
TI  - Use of sonography in assessing elbow medial collateral ligament injury after arm
      wrestling.
AB  - Medial collateral ligament injury is an infrequent occurrence in arm wrestlers.
      We report here a male patient who injured his left elbow while arm wrestling.
      Ultrasonography showed a medial collateral ligament tear. We assessed both elbows
      using ultrasonography at his 3-year follow-up visit. Dynamic ultrasonography
      showed a decreased gap at the ulnotrochlear joint space in his left elbow. A
      medial collateral ligament tear in his right elbow was also evident using
      ultrasonography. This case report shows the advantages of ultrasonography,
      especially dynamic ultrasonography, in the evaluation of elbow injury.
      Ultrasonography provides more information than valgus stress radiography,
      arthrography, and magnetic resonance imaging in the assessment of medial
      collateral ligament injury. In addition, the contralateral side can readily be
      assessed for comparison during ultrasonography. 

PMID- 24331238
TI  - Foreword.

PMID- 24331239
TI  - Management of sexual problems in cancer patients and survivors.

PMID- 24331240
TI  - The social and communication impact of stuttering on adolescents and their
      families.
AB  - PURPOSE: Stuttering can cause wide ranging psychosocial impact. This is
      particularly the case for adolescents who may face additional physical, emotional
      and personality changes as they become adults. This study reports the findings of
      an investigation into the social and communication impacts of stuttering on
      Australian adolescents seeking treatment for stuttering and their families.
      METHOD: A cross-sectional design utilising questionnaires assessed the self
      perceived communication competence and apprehension, stigma and disclosure, and
      experiences of teasing and bullying of 36 adolescents who stutter. Additionally,
      the impact of stuttering on the families of these adolescents was investigated.
      RESULTS: Adolescents who stutter have below average self-perceived communication
      competence, heightened communication apprehension, are teased and bullied more
      often than fluent peers, and they try to keep their stuttering secret. The
      families of the adolescents in the study reported high levels of emotional
      strain, family conflict and difficulty managing their child's frustrations.
      CONCLUSION: The findings from this study emphasise the wide-ranging impact of
      stuttering beyond the surface level behaviours. Clinicians working with
      adolescents who stutter should take note of both the outcomes of this study and
      the suggestions for more effectively coping with the condition in this
      population. EDUCATIONAL OBJECTIVES: The reader will be able to: (a) summarise
      findings with regards to the impact of stuttering on an adolescent's social and
      communication skills; (b) summarise areas of impact on the families of
      adolescents who stutter; (c) compare these findings with previous reported data
      for this population; (d) discuss the clinical implications of the results for
      working with adolescents who stutter and their families.

PMID- 24331242
TI  - Stuttering and work life: an interpretative phenomenological analysis.
AB  - PURPOSE: The experiential claims of nine people who stuttered were examined with
      the purpose of determining the impact of stuttering on their work lives and to
      further examine what meaning they derive from these experiences. METHOD: Six male
      and three female participants aged 29-61 years (mean age, 41.4) who stuttered
      were interviewed and verbatim interview transcripts were analyzed using
      interpretative phenomenological analysis. Credibility was established by way of
      member checking, researcher comparison with only consensual themes and
      interpretations presented in the final analysis. RESULTS: Four Superordinate
      themes, "stuttering is always there; stuttering at work reveals a problem;
      stuttering limits communication; and stuttering limits occupational progression"
      were distilled by descriptive and interpretative treatment of the interview
      transcripts. The interpretative level of analysis identified self-stigma as
      central to the meaning derived from these experiences. Participants' expectation
      of stigmatizing public attitudes, together with their own self-validation of such
      attitudes perpetuated diminished feelings about self-esteem and self-efficacy.
      Fear of negative evaluation may be heightened in the work context and might
      mediate feelings of self-stigma in this context. CONCLUSIONS: Superordinate
      themes and their subthemes indicate that stuttering is problematic at work by way
      of perpetuating in the PWS an expectation of negative evaluation by others.
      Findings implicate issues of self-stigma as generating feelings of self-doubt and
      self-reproach in PWS in the workplace. The development and effects of self-stigma
      in PWS have broader implications than the workplace context alone and further
      examination of the issues of self-stigma in stuttering is recommended.
      EDUCATIONAL OBJECTIVES: At the end of this activity the reader will be able to:
      (a) describe how stuttering might affect workplace experiences; (b) describe the
      impact of stuttering on communication in the work context; (c) describe how
      qualitative methods can provide insights into the impact of stuttering in the
      work context; (d) describe the impact of self and public stigma on wellbeing in
      the work context.

PMID- 24331241
TI  - Speech sound articulation abilities of preschool-age children who stutter.
AB  - PURPOSE: The purpose of this study was to assess the association between speech
      sound articulation and childhood stuttering in a relatively large sample of
      preschool-age children who do and do not stutter, using the Goldman-Fristoe Test
      of Articulation-2 (GFTA-2; Goldman & Fristoe, 2000). METHOD: Participants
      included 277 preschool-age children who do (CWS; n=128, 101 males) and do not
      stutter (CWNS; n=149, 76 males). Generalized estimating equations (GEE) were
      performed to assess between-group (CWS versus CWNS) differences on the GFTA-2.
      Additionally, within-group correlations were performed to explore the relation
      between CWS' speech sound articulation abilities and their stuttering frequency
      and severity, as well as their sound prolongation index (SPI; Schwartz & Conture,
      1988). RESULTS: No significant differences were found between the articulation
      scores of preschool-age CWS and CWNS. However, there was a small gender effect
      for the 5-year-old age group, with girls generally exhibiting better articulation
      scores than boys. Additional findings indicated no relation between CWS' speech
      sound articulation abilities and their stuttering frequency, severity, or SPI.
      CONCLUSIONS: Findings suggest no apparent association between speech sound
      articulation-as measured by one standardized assessment (GFTA-2)-and childhood
      stuttering for this sample of preschool-age children (N=277). EDUCATIONAL
      OBJECTIVES: After reading this article, the reader will be able to: (1) discuss
      salient issues in the articulation literature relative to children who stutter;
      (2) compare/contrast the present study's methodologies and main findings to those
      of previous studies that investigated the association between childhood
      stuttering and speech sound articulation; (3) identify future research needs
      relative to the association between childhood stuttering and speech sound
      development; (4) replicate the present study's methodology to expand this body of
      knowledge.

PMID- 24331243
TI  - The role of psychological processes in estimates of stuttering severity.
AB  - PURPOSE: To examine the associations of trait anxiety (STAI), social anxiety
      (SIAS), depression (BDI-II), and personality features (ADP-IV) with three
      measures of stuttering severity: %SS, Stuttering Severity, Instrument, and the
      Overall Assessment of the Speaker's Experience of Stuttering. METHOD: Fifty
      adults with a history of stuttering served as participants. Participant scores on
      trait, anxiety, social anxiety, depression, and personality features were entered
      into a regression analysis, with the criterion variables (DVs) being: %SS, SSI-3,
      OASES total score. In order to explore the OASES, further, each of the four OASES
      subscales were also examined. A separate regression was conducted for, each
      dependent variable. RESULTS: The OASES total score model was significant
      (p<.0001) and revealed that social anxiety and, trait anxiety were the only
      significant predictors, with medium effect sizes noted for both variables. In
      contrast, percent syllables stuttered and the SSI were not significantly
      associated with psychological, variables, suggesting that anxiety may not always
      be related to overt indicators of stuttering. Depression and personality
      dysfunction were not significantly associated with any measure of, stuttering
      severity. CONCLUSION: Anxiety in the form of social and trait anxiety are
      significantly associated with stuttering, severity as indicated by the OASES.
      Traditional procedures for assigning severity ratings to individuals, who stutter
      based on percent syllables stuttered and the Stuttering Severity Instrument are
      not, significantly related to psychological processes central to the stuttering
      experience. Depression and, personality characteristics do not meaningfully
      account for stuttering. EDUCATIONAL OBJECTIVES: The reader will be able to: (a)
      differentiate forms of anxiety that are likely to be associated with stuttering
      (b) understand the importance of determining features of stuttering that go
      beyond the obvious, surface characteristics of stuttering frequency, and (c)
      discuss the important clinical and theoretical implications for understanding the
      degree of psychological dysfunction that is likely to be characteristic of those
      who stutter.

PMID- 24331244
TI  - Psychological characteristics and perceptions of stuttering of adults who stutter
      with and without support group experience.
AB  - PURPOSE: To compare adults who stutter with and without support group experience
      on measures of self-esteem, self-efficacy, life satisfaction, self-stigma,
      perceived stuttering severity, perceived origin and future course of stuttering,
      and importance of fluency. METHOD: Participants were 279 adults who stutter
      recruited from the National Stuttering Association and Board Recognized
      Specialists in Fluency Disorders. Participants completed a Web-based survey
      comprised of various measures of well-being including the Rosenberg Self-Esteem
      Scale, Generalized Self-Efficacy Scale, Satisfaction with Life Scale, a measure
      of perceived stuttering severity, the Self-Stigma of Stuttering Scale, and other
      stuttering-related questions. RESULTS: Participants with support group experience
      as a whole demonstrated lower internalized stigma, were more likely to believe
      that they would stutter for the rest of their lives, and less likely to perceive
      production of fluent speech as being highly or moderately important when talking
      to other people, compared to participants with no support group experience.
      Individuals who joined support groups to help others feel better about themselves
      reported higher self-esteem, self-efficacy, and life satisfaction, and lower
      internalized stigma and perceived stuttering severity, compared to participants
      with no support group experience. Participants who stutter as an overall group
      demonstrated similar levels of self-esteem, higher self-efficacy, and lower life
      satisfaction compared to averages from normative data for adults who do not
      stutter. CONCLUSIONS: Findings support the notion that self-help support groups
      limit internalization of negative attitudes about the self, and that focusing on
      helping others feel better in a support group context is linked to higher levels
      of psychological well-being. EDUCATIONAL OBJECTIVES: At the end of this activity
      the reader will be able to: (a) describe the potential psychological benefits of
      stuttering self-help support groups for people who stutter, (b) contrast between
      important aspects of well-being including self-esteem self-efficacy, and life
      satisfaction, (c) summarize differences in self-esteem, self-efficacy, life
      satisfaction, self-stigma, perceived stuttering severity, and perceptions of
      stuttering between adults who stutter with and without support group experience,
      (d) summarize differences in self-esteem, self-efficacy, and life satisfaction
      between adults who stutter and normative data for adults who do not stutter.

PMID- 24331245
TI  - The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on
      neonatal type 2 diabetic rats with erectile dysfunction.
AB  - OBJECTIVE: To determine the effect of avanafil, a novel phosphodiesterase-5
      inhibitor, on the treatment of erectile dysfunction associated with type 2
      diabetes mellitus (T2DM). METHODS: In 2-day-old rats, T2DM was induced by single
      intraperitoneal injection of 90 mg/kg of streptozotocin (STZ; i.p.). Erectile
      responses were evaluated after 10 weeks on intracavernosal injection of avanafil
      (1 MUM) to anesthetized rats and data expressed as intracavernosal pressure
      (ICP)/mean arterial pressure and total ICP. The relaxant and contractile
      responses of corpus cavernosum (CC) strips were obtained in vitro studies.
      RESULTS: ICP/mean arterial pressure and total ICP responses were significantly
      reduced in T2DM rats compared with controls. Avanafil partially restored
      diminished ICP responses in diabetic rats. In CC strips from the diabetic group,
      electrical field stimulation (1-20 Hz)-induced relaxation responses were markedly
      enhanced by 45%, whereas acetylcholine (ACh; 10(-8)-10(-3))-induced relaxation
      responses were diminished by 73%. In addition, phenylephrine (PE; 10(-8)-10(-3))
      and electrical field stimulation (1-40 Hz)-induced contractile responses were
      significantly reduced in the diabetic group compared with controls. CC relaxant
      responses to sodium nitroprusside (SNP, 10(-8)-10(-3)) and avanafil (10(-8)-10(
      3)) were unaltered in both groups. CONCLUSION: The cavernous injection of
      avanafil in T2DM rats resulted in partial improvement in erectile responses.
      These findings suggest that intracavernosal administration of avanafil might be
      beneficial for the treatment of erectile dysfunction in patients with T2DM.

PMID- 24331246
TI  - Dynamic nanoimpedance characterization of the atomic force microscope tip-surface
      contact.
AB  - Nanoimpedance measurements, using the dynamic impedance spectroscopy technique,
      were carried out during loading and unloading force of a probe on three kinds of
      materials of different resistivity. These materials were: gold, boron-doped
      diamond, and AISI 304 stainless steel. Changes of impedance spectra versus
      applied force were registered and differences in the tip-to-sample contact
      character on each material were revealed. To enable comparison between materials
      and phases, a new standardization method is proposed, which simulates conditions
      of initial contact.

PMID- 24331247
TI  - Longitudinal analysis of dietary patterns in Chinese adults from 1991 to 2009.
AB  - In the present study, we aimed to identify the changes or stability in the
      structure of dietary patterns and tracking, trends and factors related to the
      adherence to these dietary patterns in China from 1991 to 2009. We analysed
      dietary data collected during seven waves of the China Health and Nutrition
      Survey and included 9253 adults with complete dietary data for three or more
      waves. Dietary intake assessment was carried out over a 3 d period with 24 h
      recalls and a household food inventory. Using factor analysis in each wave, we
      found that the structure of the two dietary patterns identified remained stable
      over the studied period. The traditional southern dietary pattern was
      characterised by high intakes of rice, fresh leafy vegetables, low-fat red meat,
      pork, organ meats, poultry and fish/seafood and low intakes of wheat flour and
      maize/coarse grains and the modern high-wheat dietary pattern was characterised
      by high intakes of wheat buns/breads, cakes/cookies/pastries, deep-fried wheat,
      nuts/seeds, starchy root/tuber products, fruits, eggs/egg products, soya milk,
      animal-based milk and instant noodles/frozen dumplings. Temporal tracking
      (maintenance of a relative position over time) was higher for the traditional
      southern dietary pattern, whereas adherence to the modern high-wheat dietary
      pattern had an upward trend over time. Higher income, education and urbanicity
      levels were positively associated with both the dietary patterns, but the
      association became weaker in the later years. These results suggest that even in
      the context of rapid economic changes in China, the way people chose to combine
      their foods remained relatively stable. However, the increasing popularity of the
      modern high-wheat dietary pattern, a pattern associated with several energy-dense
      foods, is a cause of concern.

PMID- 24331248
TI  - Translational research?

PMID- 24331249
TI  - Insomnia is associated with impaired quality of life among bariatric surgery
      candidates.
AB  - SUMMARY: Little is known about the prevalence or impact of insomnia symptoms in
      obese individuals pursuing bariatric surgery. The present study from the Rhode
      Island Bariatric Surgery (RIBS) project examined insomnia symptoms among 2300
      individuals pursuing bariatric surgery. Patients were evaluated using the
      Structured Clinical Interview for DSM-IV Disorders (SCID), Schedule for Affective
      Disorders (SADS), Rhode Island Bariatric Surgery Interview (RIBSI), and the SF-36
      as a measure of quality of life. The presence of insomnia symptoms was determined
      via ratings for the SCID items assessing initial, middle, and terminal insomnia
      symptoms, and the SADS insomnia item was used to measure severity of insomnia
      symptoms. Clinical and demographic variables were obtained from the SCID and self
      report measures. Insomnia symptoms were endorsed by 25.8% of participants.
      Bariatric patients with insomnia symptoms were rated as having a more severe
      clinical presentation and lower functioning, and were more likely to have a
      history of psychiatric treatment and/or hospitalization, compared to bariatric
      patients without insomnia. Linear regression analyses demonstrated that insomnia
      severity was a significant predictor for scores on each of the 8 SF-36 subscales
      after accounting for age, gender, race, education level, BMI, depression
      severity, and sleep apnea. Additionally, a multivariate analysis of covariance
      (MANCOVA) controlling for depression severity and sleep apnea demonstrated
      significantly poorer scores on 6 of the 8 SF-36 subscales for bariatric patients
      with current insomnia symptoms. Results revealed that insomnia symptoms are
      common among bariatric patients and are associated with reduced quality of life
      and poorer current functioning. This suggests that insomnia symptoms are an
      important clinical target in bariatric patients prior to surgery.:

PMID- 24331250
TI  - Characteristics of short sleeping time and eating behaviors related to obesity.
AB  - SUMMARY:  OBJECTIVE: To clarify the relation between short sleeping time, obesity
      and eating behaviors in male workers. METHODS: A self-completed questionnaire
      survey of 680 male daytime workers (age 19-60 years, mean age 42.9 +/- 12.5
      years) at a manufacturing plant was conducted in 2005. Subjects were divided into
      two groups by body mass index (BMI): 480 non-obese men with BMI of <25.0 kg/m(2)
      (mean age 42.8 +/- 12.8 years) and 200 obese men with BMI of >=25.0 kg/m(2) (mean
      age 43.3 +/- 11.7 years). Basic attributes and living habits were then
      investigated, and the relation of eating behavior to each BMI level was analyzed.
      BMI and eating behaviors were also investigated in relation to sleeping time.
      RESULTS: Sleeping time was significantly shorter in obese men than in non-obese
      men. Multiple regression analysis showed that sleep time as well as living with
      family were independent factors for greater BMI. BMI increased as sleeping hours
      became shorter in the order of >=9 h, 8 h, 7 h, and <=6 h. With shorter sleeping
      time, the mean eating behaviors scores also increased for cognition of
      constitution, substitution eating and drinking, feeling of satiety, meal
      contents, eating rhythm abnormalities, and eating style. The mean scores for
      these eating behaviors all increased with level of obesity, and these behaviors
      were characteristic of the obese men. CONCLUSIONS: This study showed that people
      with short sleeping times tended to have eating behaviors of eating more, which
      can lead to obesity. Short sleeping time may contribute to eating much and then
      obesity.

PMID- 24331251
TI  - Effect of weight loss on maximal fat oxidation rate in obese men.
AB  - SUMMARY:  INTRODUCTION: The hallmark features of obesity include insulin
      resistance and an impaired ability to oxidize lipids. As compared to exercise
      training, it remains relatively unclear if diet-induced weight loss can also
      induce fat metabolism. This study was undertaken to examine the effects of diet
      induced weight loss on fat metabolism during a single session of exercise in
      middle-aged obese men. METHODS: Fifteen obese men who were otherwise healthy
      (average age of 53.5 +/- 6.9 yr and average body mass index of 27.8 +/- 1.6
      kg/m(2)) participated in a 12-wk weight loss program primarily consisting of
      dietary modification. Maximal fat oxidation (MFO) rates, MFO per lean body mass
      (MFOLBM) and insulin resistance (HOMA-IR) were measured before and after the
      program. Participants performed a 24-min graded exercise test on a cycle
      ergometer, with 15-W increments every 4 min. Expired gas analysis was performed
      by indirect calorimetry, and nonprotein respiratory quotient equations were used
      to calculate fat oxidation rates. RESULTS: The weight (-8.3 +/- 3.8 kg), fat mass
      (-4.5 +/- 1.9 kg), and lean body mass (-3.8 +/- 2.4 kg) (P < 0.001 for all
      measurements) of the participants were decreased at the end of the 12-wk program.
      The MFO tended to increase by 19% (P = 0.08) and MFOLBM significantly increased
      by 28.8% (P = 0.02). Although insulin resistance also significantly decreased by
      49% (P < 0.001), changes in fat oxidation variables did not correlate with
      changes in insulin resistance. CONCLUSION: Diet-induced weight loss improves fat
      metabolism with the improvement in insulin resistance.:

PMID- 24331252
TI  - Appetite after rope skipping may differ between males and females.
AB  - SUMMARY:  BACKGROUND: When previously sedentary males and females follow the same
      exercise training programs with ad libitum feeding, males reduced body mass, but
      females do not, which suggests that females may increase appetite in response to
      exercise training compared with males. Rope skipping is traditional exercise
      modality that everyone had experienced during elementary school years in Japan.
      The purpose of this study was to determine whether there is a sex difference on
      appetite after acute rope skipping exercise. METHODS AND RESULTS: Thirteen
      healthy young males (22.5 +/- 0.8 years, 172.2 +/- 1.7 cm, 68.8 +/- 2.3 kg, 18.4
      +/- 0.9%) and 13 females (22.9 +/- 0.8 years, 160.6 +/- 1.5 cm, 52.9 +/- 1.6 kg,
      25.0 +/- 1.0%) participated in this study. Subjects consumed their lunch by
      13:00, and performed a total of 20 min rope skipping exercise (2 sets * 10 min
      with 5 min interval) from 16:00. In females, appetite significantly increased
      from immediately after the exercise to 30 min after the exercise (from 13 mm to
      30 mm), but remained unchanged in males. Although heart rate, ratings of
      perceived exertion, and lactate concentrations increased from baseline to
      immediately after exercise, there were no differences in the increase between
      males and females. Blood glucose concentrations at baseline and 30 min after
      exercise were higher in females than in males. CONCLUSION: These results
      indicated that rope skipping exercise induces an increase in appetite in females,
      but not in males. This increased appetite in females after the rope skipping
      exercise was induced without change in blood glucose concentrations.

PMID- 24331253
TI  - Possible criteria for obesity based on insulin resistance in Japanese college
      athletes.
AB  - SUMMARY:  OBJECTIVE: The purpose of this study was to search for possible
      criteria for obesity in Japanese college student athletes by examining insulin
      resistance. METHODS: The subjects were 219 male college students (mean age 20.4
      +/- 1.3 years), including 119 athletes who belonged to a university sports team
      and 100 non-athletic individuals who did not. Fasting blood glucose, hemoglobin
      A1c (HbA1c), fasting insulin and homeostasis model assessment of insulin
      resistance (HOMA-IR) levels were examined in relationship to body mass index
      (BMI) and waist circumference (WC). RESULTS: Although none of the subjects had
      diabetes mellitus, 15 (5 athletes (4.2%) and 10 non-athletes (10.0%)) had insulin
      resistance with HOMA-IR >=2.5. HOMA-IR was significantly higher in athletes with
      BMI >=27.0 kg/m(2) and non-athletes with BMI >=25.0 kg/m(2) than in subjects with
      BMI <25.0 kg/m(2). A similar pattern was seen for WC >=90 cm in athletes and >=85
      cm in non-athletes. Nearly all athletes with increased insulin resistance had BMI
      >=27.0 kg/m(2) and WC >=90 cm. Among non-athletes, nine of the 10 subjects with
      insulin resistance had BMI >=25.0 kg/m(2) and WC >=85 cm. According to these
      criteria, the sensitivity and specificity were nearly 100% and 93% for athletes,
      and 90% and 70% for non-athletes, respectively. CONCLUSION: Japanese college
      athletes may be at risk for increased insulin resistance when BMI exceeds 27.0
      kg/m(2) and WC exceeds 90 cm.

PMID- 24331254
TI  - Depression, anxiety, and neuroticism in obese patients waiting for bariatric
      surgery: Differences between patients with and without eating disorders and
      subthreshold binge eating disorders.
AB  - SUMMARY:  OBJECTIVE: This study investigated self-reported levels of depression,
      anxiety and neuroticism in obese patients waiting for bariatric surgery. The
      patients who indicated that they might have eating disorders (ED) or subthreshold
      binge eating disorders (SBED) were compared with those without. METHOD: The
      design was cross sectional. Obese patients (n = 160, 117 women, 43 men) returned
      self-report questionnaires: Eating Disorders in Obesity (EDO) indicated eating
      disorder status; Hospital Anxiety and Depression Scale (HADS) assessed symptoms
      and caseness of depression and anxiety; and the Eysenck Personality Questionnaire
      (EPQ-12) captured neuroticism. Age, BMI and gender were also recorded. RESULTS:
      Patients with ED (n = 28) presented significantly higher levels of depression,
      anxiety and neuroticism as well as more HADS-cases for depression and anxiety
      than those without ED (n = 109). Patients with sub-diagnostic binge eating
      disorders (SBED, n = 23) also reported significantly more depression symptom
      levels, and number of HADS-cases of depression, than those without ED. In
      addition, the SBED group showed significantly more neuroticism than patients
      without ED. No significant differences were found between men and women, for
      high/low age, or for high/low BMI. CONCLUSION: The data displayed that obese pre
      surgery patients with eating disorders have more psychological problems than
      those without. Patients with SBED were more similar to those with full scale
      eating disorders in their level of depression and neuroticism than those without
      ED. Clinically, obese patients with SBED should probably be regarded as those who
      have full scale ED.

PMID- 24331255
TI  - Different waist circumference measurements and prediction of cardiovascular risk
      factors and metabolic syndrome in children.
AB  - SUMMARY:  OBJECTIVE: To compare the effectiveness of three waist circumference
      (WC) measurement sites to predict cardiovascular risk factors and metabolic
      syndrome (MS) in Brazilian children. METHODS: 187 children (mean age = 9.9 +/-
      0.7 years) were evaluated for weight, height, WC at three different sites:
      midpoint between the lower rib and iliac crest (WC1), umbilicus (WC2), and
      narrowest waist (WC3). Skinfolds (triceps and subscapular) and blood pressure
      were also measured. Analyses for triglycerides, HDL-C and glucose were carried
      out in 141 children. RESULTS: For boys, the most accurate predictor of overweight
      and obesity (from body mass index, BMI) and low HDL-C levels was WC3, and for
      high percentage of body fat (from skinfolds) was WC1. For girls, WC2 was the most
      accurate predictor of MS, and hypertriglyceridemia, and for overweight and
      obesity, high body fat percentage, and low HDL-C levels, WC3 was the best
      predictor. WC1 was the most accurate in the prediction of high blood pressure.
      CONCLUSIONS: Each WC measurement site was accurate in predicting cardiovascular
      risk factors and MS. However, our results indicate that WC3 was the best
      predictor of cardiovascular risk factors and MS in boys and girls.

PMID- 24331256
TI  - Relationship between obesity in Korean adolescents and the frequency of alcohol
      consumption, the amount of alcohol consumed, and the frequency of severe alcohol
      intoxication.
AB  - SUMMARY: The purpose of this study is to determine whether the frequency of
      alcohol consumption, the amount of alcohol consumed, and the frequency of severe
      alcohol intoxication are related with obesity in Korean adolescents. In 2009,
      72,399 students from the 7th to 12th grades participated in the 5th Korea Youth
      Risk Behavior Web-based Survey (KYRBWS-V) project. Multiple logistic regression
      analyses were used to assess whether body mass index (BMI) was associated with
      the frequency of alcohol consumption, the amount of alcohol consumed, and the
      frequency of severe alcohol intoxication, after controlling for covariate
      variables such as age, parent's education level, household economic status,
      frequency of vigorous and moderate physical activities, and frequency of muscular
      strength exercises during the week, sedentary lifestyle during the week, mental
      stress, and sleep duration. No relationship was observed between the frequency of
      alcohol consumption and body weight in adolescents. However, for boys, the odds
      ratio (95% confidence interval [CI]) between becoming overweight and the amount
      of alcohol consumed was 0.678 (range, 0.534-0.862; p = 0.002) for 2 to <3 bottles
      of beer and 0.810 (range, 0.674-0.973; p = 0.025) for 3 to <4 bottles of beer.
      The odds ratio (95% CI) between becoming obese and the amount of alcohol consumed
      was 0.794 (range, 0.653-0.964; p = 0.020) for 3 to <4 bottles of beer and that
      between becoming obese and the frequency of severe alcohol intoxication was 0.758
      (range, 0.598-0.959; p = 0.021) when alcohol was consumed 1-2 times per month.
      For girls, the odds ratio (95% CI) between becoming overweight and the amount of
      alcohol consumed was 0.752 (range, 0.579-0.978; p = 0.033) for 3 to <4 bottles of
      beer and that between becoming obese and the amount of alcohol consumed was 1.753
      (range, 1.033-2.972; p = 0.037) for >=4 bottles of beer. We conclude that there
      is no relationship between the frequency of alcohol consumption and becoming
      overweight or obese. Although weight gain and obesity in boys and girls due to
      moderate consumption of alcohol are less prevalent, high alcohol consumption can
      increase weight gain in girls.:

PMID- 24331257
TI  - Relationship between body mass index and body fat in children-Age and gender
      differences.
AB  - SUMMARY: When defining obesity body mass index (BMI) has been used as the main
      criterion. However it indicates only the nutritional status, whereas body fat
      demonstrates the real body composition picture. This study aimed at analyzing the
      relationship between nutritional status and adiposity in the population of 2284
      Serbian children (1217 boys and 1067 girls). According to BMI subjects were
      divided into underweight, normal-weight, overweight and obese, and %BF values
      (based on skinfold thickness measurements) were analyzed with regard to BMI
      category, age and gender. Girls showed stronger correlation between BMI and %BF
      comparing to boys (r = 0.834 vs. 0.577). Differences in %BF between underweight,
      normal weight and overweight children from different age groups were more obvious
      in girls, whereas in boys younger than 8 years overlapping in %BF values between
      different BMI-categories was registered. In normal weight children we found age
      related oscillations in %BF values: 8- and 9-year-old boys had lower %BF
      comparing to 7-year-old boys, which was followed by %BF increasement in 10- and
      11-year-old ones; in girls %BF values gradually increased with aging, with
      significant jumps in 9-, 10- and 11-year-old ones. Thus, adiposity rebound may
      appear somehow later in boys. In overweight and obese children of both genders
      %BF continually increased with aging, whereas in underweight children %BF values
      remained unchanged. Our results pointed to age- and gender-dependent variations
      of %BF in normal weight and overweight children. We also indicated inconsistency
      between %BF and BMI especially in boys, and the need for definition of references
      for %BF.:

PMID- 24331258
TI  - Impact of body habitus on radiologic interpretations.

PMID- 24331259
TI  - Impact of body mass index on the detection of radiographic localized pleural
      thickening.
AB  - RATIONALE AND OBJECTIVES: Subpleural fat can be difficult to distinguish from
      localized pleural thickening (LPT), a marker of asbestos exposure, on chest
      radiographs. The aims of this study were to examine the influence of body mass
      index (BMI) on the performance of radiograph readers when classifying LPT and to
      model the risk of false test results with varying BMI. MATERIALS AND METHODS:
      Subjects (n = 200) were patients being screened or treated for asbestos-related
      health outcomes. A film chest radiograph, a digital chest radiograph, and a high
      resolution computed tomography (HRCT) chest scan were collected from each
      subject. All radiographs were independently read by seven B readers and scored
      using the International Labour Office system. HRCT scans, read by three
      experienced thoracic radiologists, served as the gold standard for the presence
      of LPT. We calculated measures of radiograph reader performance, including
      sensitivity and specificity, for each image modality. We also used logistic
      regression to estimate the probability of a false-positive and a false-negative
      result while controlling for covariates. RESULTS: The proportion of false
      positive readings correlated with BMI. While controlling for covariates,
      regression modeling showed the probability of a false-positive result increased
      with increasing BMI category, younger age, not having pleural calcification, and
      among subjects not reporting occupational or household contact asbestos exposure.
      CONCLUSIONS: Clinicians should be cautious when evaluating radiographs of younger
      obese persons for the presence of asbestos-related pleural plaque, particularly
      in populations having an anticipated low or background prevalence of LPT.

PMID- 24331260
TI  - Diagnostic accuracy of 18F-FDG-PET and PET/CT in the differential diagnosis
      between malignant and benign pleural lesions: a systematic review and meta
      analysis.
AB  - RATIONALE AND OBJECTIVES: To systematically review and meta-analyze published
      data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG)
      positron emission tomography (PET) and PET/computed tomography (CT) in the
      differential diagnosis between malignant and benign pleural lesions. METHODS AND
      MATERIALS: A comprehensive literature search of studies published through June
      2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the
      differential diagnosis of pleural lesions was carried out. All retrieved studies
      were reviewed and qualitatively analyzed. Pooled sensitivity, specificity,
      positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio
      (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions
      on a per-patient-based analysis were calculated. The area under the summary
      receiver operating characteristic curve (AUC) was calculated to measure the
      accuracy of these methods. Subanalyses considering device used (PET or PET/CT)
      were performed. RESULTS: Sixteen studies including 745 patients were included in
      the systematic review. The meta-analysis of 11 selected studies provided the
      following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%),
      specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05
      0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of
      the diagnostic accuracy considering PET/CT studies only was found. CONCLUSIONS:
      (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods
      in the differential diagnosis between malignant and benign pleural lesions;
      nevertheless, possible sources of false-negative and false-positive results
      should be kept in mind.

PMID- 24331261
TI  - A systematic review and meta-analysis of the accuracy of diffusion-weighted MRI
      in the detection of malignant pulmonary nodules and masses.
AB  - RATIONALE AND OBJECTIVES: To perform a meta-analysis to assess the diagnostic
      performance of the diffusion-weighted magnetic resonance imaging (DWI) technique
      in discrimination of benign and malignant pulmonary nodules or masses. MATERIALS
      AND METHODS: Data sources were studies published in PubMed, MEDLINE, EMBASE,
      Cochrane Library, and China National Knowledge Infrastructure databases from
      January 2001 to May 2013. Studies evaluating the diagnostic accuracy of DWI for
      benign/malignant discrimination of pulmonary nodules in English or Chinese
      language were considered for inclusion. Methodological quality was assessed by
      the quality assessment of diagnostic studies instrument. Sensitivities,
      specificities, predictive values, diagnostic odds ratios (DORs), and areas under
      the receiver operating characteristic curve (AUCs) were calculated. Potential
      threshold effect, heterogeneity, and publication bias were investigated. We also
      evaluated the clinical utility of DWI in diagnosis of lung lesions. RESULTS:
      Seventeen studies comprising 855 malignant and 322 benign lesions were included
      in this meta-analysis. There was no significant threshold effect. Summary
      receiver operating characteristic curve showed that AUC was 0.909 (95% confidence
      interval [CI], 0.862-0.931). Pooled weighted estimates of sensitivity,
      specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR)
      were 0.828 (95% CI, 0.801-0.853), 0.801 (95% CI, 0.753-0.843), 4.01 (95% CI, 2.78
      5.80), and 0.20 (95% CI, 0.15-0.27), respectively. Heterogeneity was found to
      have stemmed primarily from study design (retrospective or prospective study).
      Subgroup analysis showed that diagnostic performance (sensitivity, 0.88; 95% CI,
      0.82-0.92 and specificity, 0.89; 95% CI, 0.79-0.96) of retrospectively designed
      studies was significantly higher than that of prospectively designed studies. The
      Deeks' funnel plot indicated the absence of publication bias. CONCLUSIONS: With
      respect to the accuracy and DOR, DWI is useful for differentiation between
      malignant and benign pulmonary nodules or masses. Diagnostic test accuracy is not
      the be-all and end-all of diagnostic testing. Concerning PLR and NLR, DWI may not
      help to alter posttest probability compared to pretest probability to
      sufficiently alter physician's decision making. Future analyses should be
      conducted in large-scale, high-quality trials to evaluate its clinical value and
      establish standards of DWI measurement, analysis, and cutoff values of diagnosis.

PMID- 24331262
TI  - Comparison of 1D, 2D, and 3D nodule sizing methods by radiologists for spherical
      and complex nodules on thoracic CT phantom images.
AB  - RATIONALE AND OBJECTIVES: To estimate and statistically compare the bias and
      variance of radiologists measuring the size of spherical and complex synthetic
      nodules. MATERIALS AND METHODS: This study did not require the institutional
      review board approval. Six radiologists estimated the size of 10 synthetic
      nodules embedded within an anthropomorphic thorax phantom from computed
      tomography scans at 0.8- and 5-mm slice thicknesses. The readers measured the
      nodule size using unidimensional (1D) longest in-slice dimension, bidimensional
      (2D) area from longest in-slice and longest perpendicular dimension, and three
      dimensional (3D) semiautomated volume. Intercomparisons of bias (difference
      between average and true size) and variance among methods were performed after
      converting the 2D and 3D estimates to a compatible 1D scale. RESULTS: The
      relative biases of radiologists with the 3D tool were -1.8%, -0.4%, -0.7%, -0.4%,
      and -1.6% for 10-mm spherical, 20-mm spherical, 20-mm elliptical, 10-mm
      lobulated, and 10-mm spiculated nodules compared to 1.4%, -0.1%, -26.5%, -7.8%,
      and -39.8% for 1D. The three-dimensional measurements were significantly less
      biased than 1D for elliptical, lobulated, and spiculated nodules. The relative
      standard deviations for 3D were 7.5%, 3.9%, 3.6%, 9.7%, and 8.3% compared to
      5.7%, 2.6%, 20.3%, 5.3%, and 16.4% for 1D. Unidimensional sizing was
      significantly less variable than 3D for the lobulated nodule and significantly
      more variable for the ellipsoid and spiculated nodules. Three-dimensional bias
      and variability were smaller for thin 0.8-mm slice data compared to thick 5.0-mm
      data. CONCLUSIONS: The study shows that radiologist-controlled 3D volumetric
      lesion sizing can not only achieve smaller bias but also achieve similar or
      smaller variability compared to 1D sizing, especially for complex lesion shapes.

PMID- 24331264
TI  - Successful patient recruitment in CT imaging clinical trials: what factors
      influence patient participation?
AB  - RATIONALE AND OBJECTIVES: Analyze factors that influence participation in
      research studies that use coronary computed tomography (CT) imaging. MATERIALS
      AND METHODS: A 12-point survey using a questionnaire was conducted on 80
      subjects, of whom 40 agreed to participate in a cardiovascular CT imaging
      research study (enrolling subjects) and 40 declined participation (non-enrolling
      subjects). Potential factors that motivated the acceptance or refusal of
      enrollment were evaluated using a 5-point Likert scale. The following aspects
      were addressed: (1) additional health information, (2) free imaging, (3)
      altruistic benefit to society, (4) monetary compensation, (5) radiation exposure,
      (6) role as an experimental subject, (7) possible loss of confidentiality, (8)
      contrast or investigational drug use, (9) premedication use, (10) blood draw or
      intravenous placement, (11) time commitment, and (12) personal medical opinion.
      Response distributions were obtained for each question and compared between
      enrolling and non-enrolling groups. RESULTS: Enrolling subjects gave
      significantly higher ratings than non-enrolling subjects for the following
      factors: additional health information (P < .001), free imaging (P < .001), and
      the altruistic benefit to society (P < .001). For non-enrolling subjects, concern
      for possible drug use or contrast injection (P < .001), concern for possible
      premedication (P < .001), and personal availability or time commitment (P < .001)
      were all given significantly higher ratings. Concern for radiation exposure (P =
      .002) and personal medical opinion (P < .001) received significantly high ratings
      among both groups but did not differ between groups. CONCLUSIONS: Several
      influential concerns and benefits were identified from potential research
      subjects. Knowledge of what influences patient participation in studies involving
      CT imaging may allow researchers to effectively address concerns and highlight
      the potential benefits related to participation.

PMID- 24331263
TI  - Density features of screened lung tumors in low-dose computed tomography.
AB  - RATIONALE AND OBJECTIVES: Using low-dose computed tomography (LDCT), small and
      heterogeneous lung tumors are detected in screening. The criteria for assessing
      detected tumors are crucial for determining follow-up or resection strategies.
      The purpose of this study was to investigate the capacity of density features in
      differentiating lung tumors. MATERIALS AND METHODS: From July 2008 to December
      2011, 48 surgically confirmed tumors (29 malignancies, comprising 17 cases of
      adenocarcinoma and 12 cases of adenocarcinoma in situ [AdIs], and 19
      benignancies, comprising 11 cases of atypical adenomatous hyperplasia [AAH] and
      eight cases of benign non-AAH) in 38 patients were retrospectively evaluated,
      indicating that the positive predictive value (PPV) of physicians is 60.4%
      (29/48). Three types of density features, tumor disappearance rate (TDR), mean,
      and entropy, were obtained from the CT values of detected tumors. RESULTS:
      Entropy is capable of differentiating malignancy from benignancy but is limited
      in differentiating AdIs from benign non-AAH. The combination of entropy and TDR
      is effective for predicting malignancy with an accuracy of 87.5% (42/48) and a
      PPV of 89.7% (26/29), improving the PPV of physicians by 29.3%. The combination
      of entropy and mean adequately clarifies the four pathology groups with an
      accuracy of 72.9% (35/48). For tumors with a mean below -400 Hounsfield units,
      the criterion of an entropy larger than 5.4 might be appropriate for diagnosing
      malignancy. For others, the pathology is either benign non-AAH or adenocarcinoma;
      adenocarcinoma has a higher entropy than benign non-AAH, with the exception of
      tuberculoma. CONCLUSIONS: Combining density features enables differentiating
      heterogeneous lung tumors in LDCT.

PMID- 24331265
TI  - Recurrent thyroid cancer diagnosis: ROC study of the effect of a high-resolution
      head and neck 18F-FDG PET/CT scan.
AB  - RATIONALE AND OBJECTIVES: (18)F-fluorodeoxyglucose positron emission
      tomography/computed tomography ((18)F-FDG PET/CT) has demonstrated significant
      value in the evaluation of patients with indication of recurrent thyroid cancer
      with negative conventional workup. The hypothesis of this study was that the
      addition of a dedicated, high-resolution head and neck scan (HNS) to the standard
      whole-body scan (WBS) improves the accuracy of the detection and diagnosis of
      recurrent thyroid cancer. MATERIALS AND METHODS: Forty-three consecutive patients
      suspected for recurrent thyroid cancer, as indicated by increased tumor markers,
      prospectively underwent a WBS and a HNS with (18)F-FDG PET/CT. The patients were
      followed up to establish ground truth. A receiver operator characteristic (ROC)
      study with two observers was conducted to evaluate the impact of the additional
      HNS on the detection and diagnosis of recurrent thyroid cancer. Indices of
      performance included the area under the ROC curve (AUC), the number of detected
      abnormal foci, and the size of the detected foci without and with the HNS images.
      RESULTS: ROC results showed that the addition of the HNS to the standard WBS
      increased the average AUC index of performance from 0.69 to 0.96, a statistically
      significant difference with a confidence interval (CI) of -0.33 to -0.19.
      Diagnosis was also improved with the average AUC increasing from 0.79 to 0.87 but
      differences were not statistically significant (CI, -0.19 to 0.04). Interreader
      agreement was "good" in the detection task and "excellent" in the diagnostic
      task. The addition of the HNS increased the number of detected foci in the
      positive patients by an average of 37%, whereas false-positive detections in the
      negative patients increased by an average of 10%. Reported average maximum lesion
      size also increased with the HNS addition by an average of 11%. CONCLUSIONS: The
      addition of a high-resolution HNS to the standard whole-body PET/CT imaging
      improves readers' performance in the detection and diagnosis of recurrent thyroid
      cancer and could greatly benefit patient care.

PMID- 24331266
TI  - Imaging brain iron and diffusion patterns: a follow-up study of Parkinson's
      disease in the initial stages.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to examine changes of brain
      iron content and diffusion patterns longitudinally in early-stage Parkinson's
      disease (PD) patients using T2- and T2*-based magnetic resonance imaging (MRI)
      over 2-year follow-up. MATERIALS AND METHODS: We imaged 32 PD patients with
      tremor and 19 healthy controls. A follow-up study (median 25 months, range 22-31
      months) was accomplished for 25 patients (men:women = 11:14; age range 44-87
      years, median 73 years). All patients and healthy volunteers underwent clinical,
      neuropsychological, and MRI examinations on the same day. Three different MRI
      sequences were used and their results were compared: T2-weighted imaging,
      susceptibility-weighted imaging, and T2* mapping. Additionally, we evaluated
      diffusion tensor data between groups using tract-based spatial statistics.
      RESULTS: Over the 2-year follow-up, the iron-related relaxation increased in the
      globus pallidus anterior and the caudate nucleus and slightly in the substantia
      nigra pars compacta (SNc). In the globus pallidus anterior and medial SNc, the
      change was associated with mild cognitive impairment. In the caudate nucleus, the
      increase was pronounced in patients with disease onset at 67 years or older. In
      the SNc, medial transverse relaxation was increased, and in the thalamus, it was
      decreased, in patients with PD compared with healthy volunteers at 2-year follow
      up. Tract-based spatial statistical data did not differ between groups based on
      gender or Unified Parkinson's Disease Rating Scale, but a slight tendency to
      decreasing fractional anisotropy (P < .10) in the genu of corpus callosum and
      bilaterally in corona radiata was seen over 2 years. CONCLUSIONS: PD-related
      changes were found in putative iron content over 2 years. Although mild in the
      initial stages, these changes were consistent over MRI sequences. Rather than
      correlating with disease duration, the rate of changes was associated with
      individual characters, such as cognitive decline and age.

PMID- 24331267
TI  - Intraoperative ultrasound and tissue elastography measurements do not predict the
      size of hepatic microwave ablations.
AB  - RATIONALE AND OBJECTIVES: Image-guided thermal ablation is used to treat primary
      and secondary liver cancers. Evaluating completeness of ablation is difficult
      with standard intraoperative B-mode ultrasound. This study evaluates the ability
      of B-mode ultrasound (US) and tissue elastography to adequately measure the
      extent of ablation compared to pathologic assessment. MATERIALS AND METHODS: An
      in vivo porcine model was used to compare B-mode ultrasonography and elastography
      to pathologic assessment of the microwave ablation zone area. In parallel,
      intraoperative ablations in patients were used to assess the ability of B-mode US
      and elastographic measures of tissue strain immediately after ablation to predict
      ablation size, compared to postprocedural computed tomography (CT). RESULTS: In
      the animal model, ablation zones appeared to decrease in size when monitored with
      ultrasound over a 10-minute span with both B-mode US and elastography. Both
      techniques estimated smaller zones than gross pathology, however, the differences
      did not reach statistical significance. Biopsies from the edges of the ablation
      zone, as assessed by US, contained viable tissue in 75% of the cases. In the
      human model, B-mode US and elastography estimated similar ablation sizes;
      however, they underestimate the final size of the ablation defect as measured on
      postprocedure CT scan (median area [interquartile range]: CT, 7.3 cm(2) [5.2-9.5]
      vs. US 3.6 cm(2) [1.7-6.3] and elastography 4.1 cm(2) [1.4-5.1]; P = .005).
      CONCLUSIONS: Ultrasound and elastography provide an accurate gross estimation of
      ablation zone size but are unable to predict the degree of cellular injury and
      significantly underestimate the ultimate size of the ablation.

PMID- 24331268
TI  - Material decomposition images generated from spectral CT: detectability of
      urinary calculi and influencing factors.
AB  - RATIONALE AND OBJECTIVES: To evaluate the detectability of urinary calculi on
      material decomposition (MD) images generated from spectral computed tomography
      (CT) and identify the influencing factors. MATERIALS AND METHODS: Forty-six
      patients were examined with true nonenhanced (TNE) CT and spectral CT urography
      in the excretory phase. The contrast medium was removed from excretory phase
      images using water-based (WB) and calcium-based (CaB) MD analysis. The
      sensitivity for detection on WB and CaB images was evaluated using TNE results as
      the reference standard. The signal-to-noise ratio (SNR) and contrast-to-noise
      ratio (CNR) on MD images were evaluated. Using logistic regression, the
      influences of image noise, attenuation, stone size, and patient's body mass index
      (BMI) were assessed. Threshold values with maximal sensitivity and specificity
      were calculated by means of receiver operating characteristic analyses. RESULTS:
      One hundred thirty-six calculi were detected on TNE images; 98 calculi were
      identified on WB images (sensitivity, 72.06%) and 101 calculi on CaB images
      (sensitivity, 74.26%). Sensitivities were 76.92% for the 3-5-mm stones and 84.51%
      for the 5-mm or larger stones on both WB and CaB images but reduced to 46.15% on
      WB images and 53.85% on CaB images for small calculi (<3 mm). Compared to WB
      images, CaB images showed lower image noise, higher SNR but similar CNR. Larger
      stone sizes (both >2.71 mm on WB and CaB) and greater CT attenuation (>280
      Hounsfield units [HU] on WB, >215 HU on CaB) of the urinary stones were
      significantly associated with higher stone visibility rates on WB and CaB images
      (P <= .003). Image noise and BMI showed no impact on the stone detection.
      CONCLUSIONS: MD images generated from spectral CT showed good reliability for the
      detection of large (>2.71 mm) and hyperattenuating (>280 HU on WB, >215 HU on
      CaB) urinary calculi.

PMID- 24331269
TI  - Cine MR enterography grading of small bowel peristalsis: evaluation of the
      antiperistaltic effectiveness of sublingual hyoscyamine sulfate.
AB  - RATIONALE AND OBJECTIVES: To use a cine balanced steady-state free precession
      magnetic resonance enterography (cine MRE) pulse sequence to assess the
      effectiveness of a sublingual (SL) antiperistaltic agent, hyoscyamine sulfate.
      MATERIALS AND METHODS: Institutional review board approval was granted with an
      exemption for informed consent in this Health Insurance Portability and
      Accountability Act-compliant, retrospective, single-institution study. Of the 288
      MRE examinations performed between October 1, 2007 and January 15, 2011, 92 using
      SL hyoscyamine sulfate for antiperistalsis were included for review, each with
      cine MRE before and after medication. These 184 cine MRE data sets were
      randomized, blinded for treatment, and independently reviewed by five attending
      abdominal radiologists, who rated the degree of whole abdomen bowel motility on
      each cine MRE data set on a 5-point scale. Pre- and postmedication mean
      peristalsis ratings, standard deviation, mean difference, and treatment effect
      sizes were calculated. A repeated measures analysis of variance test was
      performed using a significance threshold of P = .05. Interobserver reliabilities
      were also calculated. RESULTS: Mean peristalsis ratings ranged 2.63-3.34 and 2.36
      3.03, before and after medication administration, respectively. The mean
      differences ranged from 0.22 to 0.46, which are treatment effect sizes of 0.20 to
      0.37. The decrease in peristalsis observed by the five reviewing radiologists
      after SL hyoscyamine sulfate administration was significant (df = 1/182, f =
      7.35, P < .01). The interobserver reliabilities were 0.34 for the pretest and
      0.33 for the posttest. CONCLUSIONS: Although cine MRE sequences show decreased
      bowel peristalsis after the use of SL hyoscyamine sulfate, the small size of the
      observed treatment effect is likely insufficient to justify its use for MRE.

PMID- 24331271
TI  - Mismatch in breast and detector size during screening and diagnostic mammography
      results in increased patient radiation dose.
AB  - RATIONALE AND OBJECTIVES: When using mammographic detectors of different sizes,
      it can be difficult to match patient breast size to optimal detector size. We
      studied whether a mismatch between breast size and optimal detector size resulted
      in increased radiation exposure. MATERIALS AND METHODS: All screening and
      diagnostic (Dx) mammography patients during a 6-week period in November-December
      2009 (864 patients) were evaluated (institutional review board exemption for
      quality assurance studies). Data gathered included breast size (large or small),
      detector size used, number of views obtained, mean glandular dose (MGD) per
      breast, and patient waiting time. Average MGD and average waiting time was
      calculated for imaging performed on appropriately matched or mismatched breast
      size-detector size pairs. RESULTS: Screening mammography patients with large
      breasts imaged on a small detector received a significantly higher radiation dose
      (4.9 vs. 3.3 mGy, P < .05) and a greater number of views (5.9 vs. 4.6, P < .05)
      compared to optimally matched breast-detector pairs. Dx mammography patients with
      large breasts imaged on a small detector received a higher radiation dose (8.2
      vs. 6.7 mGy, P < .05) compared to optimally matched breast-detector pairs,
      although without an increased number of views. Waiting times were longer for a
      large detector. CONCLUSIONS: A mismatch in breast-detector sizes results in a
      significantly greater radiation dose to patients with large breasts imaged on a
      small detector. Pressure to minimize patient waiting time may inadvertently
      result in increased radiation dose. Detector size should be matched to breast
      size whenever possible, but particularly for patients with larger breast sizes.

PMID- 24331270
TI  - Preoperative MRI improves prediction of extensive occult axillary lymph node
      metastases in breast cancer patients with a positive sentinel lymph node biopsy.
AB  - RATIONALE AND OBJECTIVES: To test the ability of quantitative measures from
      preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to
      predict, independently and/or with the Katz pathologic nomogram, which breast
      cancer patients with a positive sentinel lymph node biopsy will have four or more
      positive axillary lymph nodes on completion axillary dissection. MATERIALS AND
      METHODS: A retrospective review was conducted to identify clinically node
      negative invasive breast cancer patients who underwent preoperative DCE-MRI,
      followed by sentinel node biopsy with positive findings and complete axillary
      dissection (June 2005-January 2010). Clinical/pathologic factors, primary lesion
      size, and quantitative DCE-MRI kinetics were collected from clinical records and
      prospective databases. DCE-MRI parameters with univariate significance (P < .05)
      to predict four or more positive axillary nodes were modeled with stepwise
      regression and compared to the Katz nomogram alone and to a combined MRI-Katz
      nomogram model. RESULTS: Ninety-eight patients with 99 positive sentinel biopsies
      met study criteria. Stepwise regression identified DCE-MRI total persistent
      enhancement and volume adjusted peak enhancement as significant predictors of
      four or more metastatic nodes. Receiver operating characteristic curves
      demonstrated an area under the curve of 0.78 for the Katz nomogram, 0.79 for the
      DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The
      combined model was significantly more predictive than the Katz nomogram alone (P
      = .003). CONCLUSIONS: Integration of DCE-MRI primary lesion kinetics
      significantly improved the Katz pathologic nomogram accuracy to predict the
      presence of metastases in four or more nodes. DCE-MRI may help identify sentinel
      node-positive patients requiring further local-regional therapy.

PMID- 24331273
TI  - The pitfalls of prestige and dominance in leadership education.

PMID- 24331272
TI  - A knowledge-based iterative model reconstruction algorithm: can super-low-dose
      cardiac CT be applicable in clinical settings?
AB  - RATIONALE AND OBJECTIVES: To investigate whether "full" iterative reconstruction,
      a knowledge-based iterative model reconstruction (IMR), enables radiation dose
      reduction by 80% at cardiac computed tomography (CT). MATERIALS AND METHODS: A
      total of 23 patients (15 men, eight women; mean age 64.3 +/- 13.4 years) who
      underwent retrospectively electrocardiography-gated cardiac CT with dose
      modulation were evaluated. We compared full-dose (FD; 730 mAs) images
      reconstructed with filtered back projection (FBP) technique and the low-dose (LD;
      146 mAs) images reconstructed with FBP and IMR techniques. Objective and
      subjective image quality parameters were compared among the three different CT
      images. RESULTS: There was no significant difference in the CT attenuation among
      the three reconstructions. The mean image noise of LD-IMR (18.3 +/- 10.6
      Hounsfield units [HU]) was significantly lowest among the three reconstructions
      (41.9 +/- 15.3 HU for FD-FBP and 109.9 +/- 42.6 HU for LD-FBP; P < .01). The
      contrast-to-noise ratio of LD-IMR was better than that of FD-FBP and LD-FBP (P <
      .01). Visual evaluation score was also highest for LD-IMR. CONCLUSIONS: The IMR
      can provide improved image quality at super-low-dose cardiac CT with 20% of the
      standard tube current.

PMID- 24331274
TI  - Comparative accuracy of intravenous contrast-enhanced CT versus noncontrast CT
      plus intravenous contrast-enhanced CT in the detection and characterization of
      patients with hypervascular liver metastases: a critically appraised topic.
AB  - RATIONAL AND OBJECTIVES: To evaluate whether addition of nonenhanced computed
      tomography (NECT) to intravenous contrast-enhanced (CE) abdominal CT improves
      detection or characterization of hypervascular liver masses. Patients were
      referred for initial staging or follow-up with known breast, melanoma,
      neuroendocrine, or thyroid cancer. MATERIAL AND METHODS: The literature was
      searched using the patient, intervention, comparison, and outcome (PICO) method.
      Retrieved articles were critically appraised and assigned a level of evidence
      based on the Oxford University Centre for Evidence-based Medicine hierarchy of
      validity for diagnostic studies. RESULTS: One thousand one hundred studies were
      reviewed; only 11 studies matched the PICO of our study and were appraised. Most
      of the appraised articles were published in the 1990s using older technology and
      contrast delivery. The retrieved diagnostic performance for characterization of
      liver metastases showed sensitivity/specificity of 97%/76% for NECT, 97%/75% for
      arterial CT, and 98%/76% for portal venous phase CT in patients with breast
      cancer; sensitivity of 96% (arterial and portal CT) versus 100% (NECT, arterial
      and portal CT) in patients with melanoma; and sensitivity of 43% (portal CT)
      versus 17% (NECT) in patients with neuroendocrine tumor. No primary study was
      found for performance of different CT protocols in patients with thyroid cancer.
      Available evidence showed radiologists reported more conspicuous liver masses on
      CECT compared to NECT in patients with breast or neuroendocrine cancer.
      CONCLUSIONS: Based on existing evidence, NECT only adds a small incremental value
      to CECT for detection/characterization of hypervascular liver metastases.
      Addition of NECT increases patient's exposure to radiation and the number of
      images available for interpretation.

PMID- 24331275
TI  - Improvement in reporting skills of radiology residents with a structured
      reporting curriculum.
AB  - RATIONALE AND OBJECTIVES: Radiology residents must acquire dictation and
      reporting skills to meet Accreditation Council for Graduate Medical Examination
      requirements and provide optimal patient care. Historically, these skills have
      been taught informally and vary between institutions and among radiologists. A
      structured curriculum improves resident report quality when using a quantitative
      grading scheme. This study describes the implementation of such a curriculum and
      evaluates its utility in tracking resident progress. MATERIALS AND METHODS: We
      implemented a three-stage reporting curriculum in our diagnostic radiology
      residency program in 2009. Stages 1 and 2 involve instruction and formative
      feedback composed of suggestions for improvement in a 360 degrees  format from
      faculty, peers, and others within the resident's sphere of influence. The third
      stage involves individual, biannual, written feedback with scored reports
      specifically assessing four categories: succinctness, spelling/grammar, clarity,
      and responsible referral. Biannual scores were collected from 2009 to 2013,
      sorted by year of residency training (R1 to R4), and average training level
      scores were statistically compared. RESULTS: Review of 1500 reports over a 4-year
      period yielded a total of 153 scores: 54, 36, 29, and 34 from R1, R2, R3, and R4
      residents, respectively. The mean (standard deviation) scores for R1, R2, R3, and
      R4 residents were 10.20 (1.06), 10.25 (0.81), 10.5 (0.74), and 10.75 (0.69),
      respectively. Post hoc analysis identified significant differences between R1 and
      R4 residents (P = .012) and R2 and R4 residents (P = .009). CONCLUSIONS:
      Residents' reporting scores showed significant improvement over the course of
      their residency training. This indicates that there may be a benefit in using an
      organized reporting curriculum to track resident progress in producing reports
      that may improve patient care.

PMID- 24331277
TI  - Patient activation, depression and quality of life.
AB  - OBJECTIVE: "Patient activation" describes the extent to which individuals manage
      their own healthcare. This study evaluated the association of patient activation,
      depressive symptoms and quality of life in a primary care setting. METHODS: 278
      patients who visited two primary care clinics were interviewed in the waiting
      room before their appointment or by telephone. Study participants completed the
      Patient Activation Measure (PAM), Patient Health Questionnaire-9 (PHQ-9) and
      Short Form-12 Health Survey (SF-12). Physicians assessed each participant's
      depression status immediately after the visit. RESULTS: PAM scores correlated
      negatively with PHQ-9 (r=-0.35, p<0.0001) and positively with total SF-12 score
      (r=0.39, p<0.0001). Increased participant involvement by one-level increments on
      the PAM was predicted by their being in the 55 to 74-year age group and higher
      total SF-12 quartiles. Almost half of those scoring >=10 on PHQ-9 were not
      considered depressed by their physician (false negatives, i.e. "hidden
      depression"). CONCLUSION: In primary care settings, PAM is easily administered
      and useful for general patients and for those with depressive symptoms. PRACTICE
      IMPLICATIONS: Assessing patient activation will enable caregivers to monitor
      levels of self-care (activation) and potential adherence to health behavior
      recommendations. PHQ-9 screening could increase awareness of "hidden depression"
      in the primary care setting.

PMID- 24331278
TI  - Can providing feedback on driving behavior and training on parental vigilant care
      affect male teen drivers and their parents?
AB  - This study focuses on investigating the driving behavior of young novice male
      drivers during the first year of driving (three months of accompanied driving and
      the following nine months of solo driving). The study's objective is to examine
      the potential of various feedback forms on driving to affect young drivers'
      behavior and to mitigate the transition from accompanied to solo driving. The
      study examines also the utility of providing parents with guidance on how to
      exercise vigilant care regarding their teens' driving. Driving behavior was
      evaluated using data collected by In-Vehicle Data Recorders (IVDR), which
      document events of extreme g-forces measured in the vehicles. IVDR systems were
      installed in 242 cars of the families of young male drivers, however, only 217
      families of young drivers aged 17-22 (M=17.5; SD=0.8) completed the one year
      period. The families were randomly allocated into 4 groups: (1) Family feedback:
      In which all the members of the family were exposed to feedback on their own
      driving and on that of the other family members; (2) Parental training: in which
      in addition to the family feedback, parents received personal guidance on ways to
      enhance vigilant care regarding their sons' driving; (3) Individual feedback: In
      which family members received feedback only on their own driving behavior (and
      were not exposed to the data on other family members); (4) CONTROL: Group that
      received no feedback at all. The feedback was provided to the different groups
      starting from the solo period, thus, the feedback was not provided during the
      supervised period. The data collected by the IVDRs was first analyzed using
      analysis of variance in order to compare the groups with respect to their monthly
      event rates. Events' rates are defined as the number of events in a trip divided
      by its duration. This was followed by the development and estimation of random
      effect negative binomial models that explain the monthly event rates of young
      drivers and their parents. The study showed that: (1) the Parental training group
      recorded significantly lower events rates (-29%) compared to the CONTROL group
      during the solo period; (2) although directed mainly at the novice drivers, the
      intervention positively affected also the behavior of parents, with both fathers
      and mothers in the Parental training group improving their driving (by -23% for
      both fathers and mothers) and mothers improving it also in the Family feedback
      group (by -30%). Thus, the intervention has broader impact effect beside the
      targeted population. It can be concluded that providing feedback on driving
      behavior and parental training in vigilant care significantly improves the
      driving behavior of young novice male drivers. Future research directions could
      include applying the intervention to a broader population, with larger diversity
      with respect to their driving records, culture, and behaviors. The challenge is
      to reach wide dissemination of IVDR for young drivers accompanied by parents'
      involvement, and to find the suitable incentives for its sustainability. 

PMID- 24331279
TI  - A tool for rating chronic disease prevention and public health interventions.
AB  - Bridging the gap between research and practice requires more than evaluating the
      effectiveness of interventions in controlled studies. To bridge this gap,
      evidence needs to be defined in different ways, and opportunities need to be
      provided for practice-based evidence to be replicated and disseminated. Community
      based interventions are often not conducted or evaluated in controlled settings,
      yet they provide more real-world context and have the potential to have a greater
      effect on population health than findings from controlled studies that are
      limited in generalizability. The purpose of this article is to describe an
      approach to identify community-based programs and interventions that have the
      potential for replication and dissemination. In our study, such interventions met
      criteria in 3 primary domains: innovativeness, effectiveness, and sustainability.
      The criteria and tool developed were applied to 2 obesity-prevention programs to
      demonstrate the usefulness of the tool for identifying potential programs for
      replication and dissemination, contributing to practice-based evidence. Funders,
      practitioners, and researchers can apply these criteria to identify programs,
      environmental changes, or policies that may be replicated and disseminated. 

PMID- 24331280
TI  - Seeking best practices: a conceptual framework for planning and improving
      evidence-based practices.
AB  - How can we encourage ongoing development, refinement, and evaluation of practices
      to identify and build an evidence base for best practices? On the basis of a
      review of the literature and expert input, we worked iteratively to create a
      framework with 2 interrelated components. The first - public health impact -
      consists of 5 elements: effectiveness, reach, feasibility, sustainability, and
      transferability. The second - quality of evidence - consists of 4 levels, ranging
      from weak to rigorous. At the intersection of public health impact and quality of
      evidence, a continuum of evidence-based practice emerges, representing the
      ongoing development of knowledge across 4 stages: emerging, promising, leading,
      and best. This conceptual framework brings together important aspects of impact
      and quality to provide a common lexicon and criteria for assessing and
      strengthening public health practice. We hope this work will invite and advance
      dialogue among public health practitioners and decision makers to build and
      strengthen a diverse evidence base for public health programs and strategies. 

PMID- 24331281
TI  - Characteristics of successful community partnerships to promote physical activity
      among young people, North Carolina, 2010-2012.
AB  - INTRODUCTION: Success of community-based projects has been thought to hinge on
      the strength of partnerships between those involved in design and implementation.
      However, characteristics of successful partnerships have not been fully
      described, particularly in the context of community-based physical activity
      promotion. We sought to identify characteristics of successful partnerships from
      the perspective of project coordinators involved in a mini-grant program to
      promote physical activity among young people. METHODS: Semistructured qualitative
      interviews were conducted with county coordinators (n = 19) of 20 North
      Carolina's "Eat Smart, Move More" Community Grants projects funded during 2010
      through 2012. Emergent themes were coded; then, overarching themes in the coded
      data were identified and grouped with similar codes under thematic headings. On
      the basis of project coordinators' responses, each partnership was classified as
      strong, moderate, or weak. RESULTS: Three overarching themes characterized
      partnership relationships: continuity (history with partner and willingness to
      engage in a future partnership), community connectedness, and capacity (interest,
      enthusiasm, engagement, communication, and clarity of roles and
      responsibilities). Strong partnerships were those in which project coordinators
      indicated a positive working history with partners, experienced a high level of
      engagement from partners, had clearly defined roles and responsibilities of
      partners, and expressed a clear interest in working with their partners in the
      future. CONCLUSION: In community partnerships aimed at increasing physical
      activity among young people, the perspectives of project coordinators are vital
      to identifying the characteristics of strong, moderate, and weak partnerships.
      These perspectives will be useful for future community program development and
      will influence potential health outcomes.

PMID- 24331282
TI  - Effects of messages emphasizing environmental determinants of obesity on
      intentions to engage in diet and exercise behaviors.
AB  - INTRODUCTION: Reducing rates of obesity will require interventions that influence
      both individual decisions and environmental factors through changes in public
      policy. Previous work indicates that messages emphasizing environmental
      determinants increases support for public policies, but some suspect this
      strategy may undermine motivation to engage in diet and exercise. METHODS: Study
      1 involved 485 adults recruited from a shopping mall in New York. Study 2
      involved 718 adult members of a Web-based national panel of US adults.
      Respondents in both studies were randomly assigned to read a story that
      emphasized environmental determinants of health or a control condition. The
      stories varied in the extent to which they described the story character as
      taking personal responsibility for weight management. Logistic regression and
      ordered logit models were used to test for differences in intentions to engage in
      diet and exercise behaviors based on which story the participant read. Analyses
      were also performed separately by participants' weight status. RESULTS: In both
      studies, messages that acknowledged personal responsibility while emphasizing
      environmental causes of obesity increased intentions to engage in healthy
      behavior for at least 1 weight status group. CONCLUSION: Emphasizing factors
      outside of personal control appears to enhance rather than undermine motivations
      to engage in healthy diet and exercise behavior.

PMID- 24331283
TI  - Diagnostic validity and the definition of mental disorder: a program for
      conceptually advancing psychiatry.

PMID- 24331284
TI  - What is a mental disorder? A perspective from cognitive-affective science.
AB  - Defining disease and disorder remains a key conceptual question in philosophy of
      medicine and psychiatry, and is currently a very practical matter for psychiatric
      nosology, given the new Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition, and the upcoming International Classification of Diseases, 11th
      Revision. There have been advances in the cognitive-affective science of human
      categorization, and it is timely to consider implications for our understanding
      of the category of psychiatric disorder. The category of mental disorder has
      graded boundaries, and conditions within this category can be conceptualized
      using MEDICAL or MORAL metaphors. One key set of constructs used in MEDICAL
      metaphors relates to the notion of dysfunction, and it may, in turn, be useful to
      conceptualize such dysfunction in evolutionary terms. For typical disorders, it
      is relatively easy to agree that dysfunction is present. However, for atypical
      disorders, there may be considerable debate about the presence and extent of
      dysfunction. Rational arguments can be brought to bear to help decide whether
      particular entities should be included in our nosologies, and, if so, what their
      boundaries should be. However, it is appropriate that there should be ongoing
      debate on diagnostic validity, clinical utility, and other relevant facts and
      values, for cases that are difficult to decide. The perspective here can be
      illustrated using many nosological debates within the anxiety disorders and the
      obsessive-compulsive and related disorders, including the question of delineating
      normal from abnormal anxiety, of deciding whether anxiety is psychiatric or
      medical, and the debate about the optimal meta-structure for anxiety disorders. 

PMID- 24331285
TI  - Diagnostic criteria as dysfunction indicators: bridging the chasm between the
      definition of mental disorder and diagnostic criteria for specific disorders.
AB  - According to the introduction to the Diagnostic and Statistical Manual of Mental
      Disorders (DSM), Fifth Edition, each disorder must satisfy the definition of
      mental disorder, which requires the presence of both harm and dysfunction.
      Constructing criteria sets to require harm is relatively straightforward.
      However, establishing the presence of dysfunction is necessarily inferential
      because of the lack of knowledge of internal psychological and biological
      processes and their functions and dysfunctions. Given that virtually every
      psychiatric symptom characteristic of a DSM disorder can occur under some
      circumstances in a normally functioning person, diagnostic criteria based on
      symptoms must be constructed so that the symptoms indicate an internal
      dysfunction, and are thus inherently pathosuggestive. In this paper, we review
      strategies used in DSM criteria sets for increasing the pathosuggestiveness of
      symptoms to ensure that the disorder meets the requirements of the definition of
      mental disorder. Strategies include the following: requiring a minimum duration
      and persistence; requiring that the frequency or intensity of a symptom exceed
      that seen in normal people; requiring disproportionality of symptoms, given the
      context; requiring pervasiveness of symptom expression across contexts; adding
      specific exclusions for contextual scenarios in which symptoms are best
      understood as normal reactions; combining symptoms to increase cumulative
      pathosuggestiveness; and requiring enough symptoms from an overall syndrome to
      meet a minimum threshold of pathosuggestiveness. We propose that future revisions
      of the DSM consider systematic implementation of these strategies in the
      construction and revision of criteria sets, with the goal of maximizing the
      pathosuggestiveness of diagnostic criteria to reduce the potential for diagnostic
      false positives. 

PMID- 24331286
TI  - Distinctive trajectory groups of mental health functioning among assertive
      community treatment clients: an application of growth mixture modelling analysis.
AB  - OBJECTIVE: Assertive community treatment (ACT) studies that have used
      conventional, statistical growth modelling methods have not examined different
      trajectories of outcomes or covariates that could influence different
      trajectories, even though heterogeneity in outcomes has been established in other
      research on severe mental illness. The purpose of our study was to examine the
      general trend in mental health functioning of ACT clients over a 2-year follow-up
      time period, to discover groups of ACT clients with distinctive longitudinal
      trajectories of mental health functioning, and to examine if some of the key
      sociodemographic and illness-related factors influence group membership. METHOD:
      A 2-year, prospective, within-subjects study of 216 ACT clients within southern
      Ontario, collected functional outcome data at baseline and 12 and 24 months using
      the Colorado Client Assessment Record. Baseline covariates included sex, primary
      diagnosis, number of comorbidities, hospitalization history, and duration of
      illness. Growth mixture modelling (GMM) was used to examine trajectories.
      RESULTS: Clinical staff assessments of ACT clients showed a statistically
      significant improvement in functioning and 84% achieved successful community
      tenure. GMM analysis identified 2 classes of ACT clients: class 1 (79.63% of
      clients) experienced lower and stable overall functioning, and class 2 (20.37%)
      showed a better baseline functioning score and improvement in the overall
      functioning over time. Class membership was predicted by the number of
      comorbidities and diagnosis. CONCLUSIONS: Our study suggests general stability in
      overall functioning for the sampled ACT clients over 2 years, but significant
      heterogeneity in trajectories of functioning.

PMID- 24331287
TI  - Functional impairment in patients with major depressive disorder and comorbid
      anxiety disorder.
AB  - OBJECTIVE: To analyze the potential for different aspects of anxiety to modify
      the effect of impaired functioning in major depressive disorder (MDD). METHODS:
      Participants (n = 1226) were psychiatric outpatients with MDD. A cross-sectional,
      multicentre, nationwide study was designed. The 12-item version of the World
      Health Organization Disability Assessment Schedule II was used to assess
      functional limitation. Anxiety was measured using the Hamilton Anxiety Rating
      Scale and the State-Trait Anxiety Inventory (STAI). Depression severity was
      measured using the Quick Inventory of Depressive Symptomatology. RESULTS: About
      43.1% of patients had a comorbid MDD and anxiety disorder. Poorer functioning
      correlated significantly with severity of depression (Pearson r = 0.78, P =
      0.001), severity of anxiety (r = 0.65, P = 0.001), and higher anxiety trait
      scores (r = 0.40, P = 0.001), but not significantly with STAI-State scores (r =
      0.03, P = 0.26). The overall regression model was significant and explained 66%
      of the functioning variability in patients with MDD, mostly attributable to
      depression severity. Results indicate that anxiety has a moderate impact on
      functioning impairment in patients with MDD. CONCLUSIONS: Our findings suggest
      that MDD and anxiety severity appear to be associated significantly with impaired
      functioning in patients with MDD but explains only a moderate proportion of
      variance.

PMID- 24331288
TI  - Changes in mindfulness following repetitive transcranial magnetic stimulation for
      mood disorders.
AB  - OBJECTIVE: Mindfulness practices are associated with changes in different
      cortical regions, including the dorsolateral prefrontal cortices (DLPFCs). Our
      study sought to examine how an index course of repetitive transcranial magnetic
      stimulation (rTMS) over the DLPFC improved components of mindfulness as assessed
      by Baer's Five Facet Mindfulness Questionnaire (FFMQ) and the Experience
      Questionnaire (EQ). METHOD: Our preliminary study is a retrospective chart review
      of 32 patients who had undergone an index course of rTMS for major depressive
      episode between 2009 and 2012. The following information was collected prior to
      rTMS: patient demographics, diagnosis, and age of onset of primary diagnosis. The
      following information was collected prior to and after rTMS: 21-item Hamilton
      Rating Scale for Depression (HRSD) scores, Patient-Health Questionnaire (PHQ-9)
      scores, Generalized Anxiety Disorder 7-item (GAD-7) scale scores, FFMQ scores,
      and EQ scores. RESULTS: Following rTMS, results showed statistically significant
      decreases in HRSD, PHQ-9, and GAD-7 scores. There was significant improvement in
      the nonreactivity to inner experience subscale of the BFFMQ and in the decentring
      subscale of the EQ. Subgroup analysis between patients who did not improve on the
      HRSD by 50% or more following rTMS and those who did revealed no baseline
      difference in mindfulness. There was significant improvement in the decentring
      subscale of the EQ in both subgroups. CONCLUSIONS: Our study provides preliminary
      data that rTMS may be associated with improvement in some components of
      mindfulness, independently of changes in depression.

PMID- 24331289
TI  - Depression screening in primary care: why the Canadian task force on preventive
      health care did the right thing.
AB  - OBJECTIVE: To review the recent recommendation against routinely screening adults
      for depression in primary care settings by the Canadian Task Force on Preventive
      Health Care (CTFPHC). METHODS: We reviewed the CTFPHC recommendation and
      discussed it in the context of relevant evidence. RESULTS: Depression screening,
      which involves using depression symptom questionnaires to attempt to identify
      patients who have unrecognized depression, was previously recommended by the
      CTFPHC in primary care settings with staff-assisted depression care programs in
      place to ensure accurate diagnosis, effective treatment, and follow-up, but not
      in the absence of such programs. The CTFPHC recently updated this guideline and
      recommended against routinely screening adults for depression in primary care
      because there have not been any randomized controlled trials (RCTs) that have
      shown depression screening to be beneficial and because of a concern about the
      potentially high number of false-positive screens that would occur. Without
      evidence from RCTs of better health outcomes from screening, there are numerous
      factors that suggest that depression screening, even with collaborative
      depression care, may not be beneficial for patients, including the high rate of
      patients already treated, uncertainty about the ability of depression screening
      tools to accurately identify previously unrecognized patients, and relatively
      small treatment effects among patients with less severe depression who would be
      most likely to be identified through screening. Routine screening would expose
      some patients to avoidable risks and would pose a significant cost burden.
      CONCLUSION: The CTFPHC recommendation to not screen for depression in primary
      care is consistent with available evidence. Clinicians in primary care settings
      should be alert to signs of depression and attend to symptoms through assessment
      and, as appropriate, referral or management, as recommended by the CTFPHC.

PMID- 24331290
TI  - The genome- and system-wide response of DNA methylation to early life adversity
      and its implication on mental health.
AB  - Early life adversity is associated with long-tem impacts on behaviour and
      physical and mental health. The mechanisms mediating the impact of early life
      environment on the phenotype are proposed to involve a change in the state of
      deoxyribonucleic acid (DNA) methylation and, as a consequence, in the stable
      programming of gene expression. Recent studies suggest that the changes in DNA
      methylation affect broad genomic regions, as well as peripheral tissues in
      addition to brain regions. Although the data are still scarce, it points to the
      possibility that DNA methylation is a mechanism of genome adaptation to signals
      from early life social environment. This modulation of the DNA methylation
      pattern is proposed to result in long-term impact on the phenotype that could
      become maladaptive under certain contexts later in life. This model has
      implications on our understanding of behavioural and mental health pathologies,
      as well as their diagnosis and therapeutics. 

PMID- 24331291
TI  - Depression and use of antidepressants in Swedish nursing homes: a 12-month follow
      up study.
AB  - BACKGROUND: The prescription of antidepressants in nursing homes has increased
      markedly since the introduction of SSRIs, while at the same time depressive
      symptoms often go unrecognized and untreated. The aim of this study was to
      examine whether depression among residents in nursing homes is treated
      adequately. METHODS: A sample of 429 participants from 11 Swedish nursing homes
      was selected and was assessed with the Cornell Scale for Depression in Dementia
      (CSDD) and using medical records and drug prescription data. For 256 participants
      a follow-up assessment was performed after 12 months. RESULTS: The prevalence of
      depression, according to medical records, was 9.1%, and the prevalence of CSDD
      score of >=8 was 7.5%. Depression persisted in more than 50% of cases at the 12
      month follow-up. Antidepressants were prescribed to 33% of the participants
      without a depression diagnosis or with a CSDD score of <8. 46.2% of all
      participants were prescribed antidepressants. 14% of the participants without a
      depression diagnosis or with a CSDD score of <8 had psychotropic polypharmacy.
      15.2% of all participants had psychotropic polypharmacy, which persisted at the
      12-month follow-up in three-quarters of cases. CONCLUSION: The prescription of
      antidepressants in frail elderly individuals is extensive and may be without
      clear indication. The clinical implication is that there is a need for systematic
      drug reviews at nursing homes, paying special attention to the subjects which are
      on antidepressants.

PMID- 24331292
TI  - Sample thickness determination by scanning transmission electron microscopy at
      low electron energies.
AB  - Sample thickness is a decisive parameter for any quantification of image
      information and composition in transmission electron microscopy. In this context,
      we present a method to determine the local sample thickness by scanning
      transmission electron microscopy at primary energies below 30 keV. The image
      intensity is measured with respect to the intensity of the incident electron beam
      and can be directly compared with Monte Carlo simulations. Screened Rutherford
      and Mott scattering cross-sections are evaluated with respect to fitting
      experimental data with simulated image intensities as a function of the atomic
      number of the sample material and primary electron energy. The presented method
      is tested for sample materials covering a wide range of atomic numbers Z, that
      is, fluorenyl hexa-peri-hexabenzocoronene (Z = 3.5), carbon (Z = 6), silicon (Z =
      14), gallium nitride (Z = 19), and tungsten (Z = 74). Investigations were
      conducted for two primary energies (15 and 30 keV) and a sample thickness range
      between 50 and 400 nm. 

PMID- 24331293
TI  - Genistein decreases the breast cancer stem-like cell population through Hedgehog
      pathway.
AB  - INTRODUCTION: The existence of breast cancer stem-like cells (BCSCs) has profound
      implications for cancer prevention. Genistein, a predominant isoflavone found in
      soy products, has multiple robust anti-tumor effects in various cancers,
      especially in the breast and prostate cancer. In this study, we aimed to evaluate
      genistein inhibition of BCSCs and its potential mechanism by culturing MCF-7
      breast cancer cells and implanting these cells into nude mice. METHODS: Cell
      counting, colony formation and cell apoptosis analysis were used to evaluate the
      effect of genistein on breast cancer cells' growth, proliferation and apoptosis.
      We then used mammosphere formation assay and CD44CD24 staining to evaluate the
      effect of genistein on BCSCs in vitro. A nude mice xenograft model was employed
      to determine whether genistein could target BCSCs in vivo, as assessed by real
      time polymerase chain reaction (PCR) and immunohistochemical staining. The
      potential mechanism was investigated utilizing real-time PCR, western blotting
      analysis and immunohistochemical staining. RESULTS: Genistein inhibited the MCF-7
      breast cancer cells' growth and proliferation and promoted apoptosis. Both in
      vitro and in vivo genistein decreased breast cancer stem cells, and inhibited
      breast cancer stem-like cells through down-regulation of the Hedgehog-Gli1
      Signaling Pathway. CONCLUSIONS: We demonstrated for the first time that genistein
      inhibits BCSCs by down-regulating Hedgehog-Gli1 signaling pathway. These findings
      provide support and rationale for investigating the clinical application of
      genistein in treating breast cancer, and specifically by targeting breast cancer
      stem cells.

PMID- 24331294
TI  - EASL Clinical Practice Guidelines: management of hepatitis C virus infection.

PMID- 24331295
TI  - Assessment of the dietary intake of total flavan-3-ols, monomeric flavan-3-ols,
      proanthocyanidins and theaflavins in the European Union.
AB  - Dietary interventions with flavan-3-ols have shown beneficial effects on vascular
      function. The translation of these findings into the context of the health of the
      general public requires detailed information on habitual dietary intake. However,
      only limited data are currently available for European populations. Therefore, in
      the present study, we assessed the habitual intake of flavan-3-ol monomers,
      proanthocyanidins (PA) and theaflavins in the European Union (EU) and determined
      their main food sources using the EFSA (European Food Safety Authority)
      Comprehensive European Food Consumption Database. Data for adults aged 18-64
      years were available from fourteen European countries, and intake was determined
      using the FLAVIOLA Flavanol Food Composition Database, developed for the present
      study and based on the latest US Department of Agriculture and Phenol-Explorer
      databases. The mean habitual intake of flavan-3-ol monomers, theaflavins and PA
      ranged from 181 mg/d (Czech Republic) to 793 mg/d (Ireland). The highest intakes
      of flavan-3-ol monomers and theaflavins were observed in Ireland (191/505 mg/d)
      and the lowest intakes in Spain (24/9 mg/d). In contrast, the daily intake of PA
      was highest in Spain (175 mg/d) and lowest in The Netherlands (96 mg/d). Main
      sources were tea (62%), pome fruits (11%), berries (3%) and cocoa products (3%).
      Tea was the major single contributor to monomer intake (75%), followed by pome
      fruits (6%). Pome fruits were also the main source of PA (28%). The present study
      provides important data on the population-based intake of flavanols in the EU and
      demonstrates that dietary intake amounts for flavan-3-ol monomers, PA and
      theaflavins vary significantly across European countries. The average habitual
      intake of flavan-3-ols is considerably below the amounts used in most dietary
      intervention studies.

PMID- 24331296
TI  - Balance control in lower extremity amputees during quiet standing: a systematic
      review.
AB  - Postural control has been widely evaluated for the normal population and
      different groups over the past 20 years. Numerous studies have investigated
      postural control in quiet standing posture among amputees. However, a
      comprehensive analysis is lacking on the possible contributing factors to
      balance. The present systematic review highlights the current findings on
      variables that contribute to balance instability for lower extremity amputees.
      The search strategy was performed on PubMed, Web of Science, Medline, Scopus, and
      CINAHL and then followed by additional manual searching via reference lists in
      the reviewed articles. The quality of the articles was evaluated using a
      methodological quality assessment tool. This review included and evaluated a
      total of 23 full-text articles. Despite the inconsistencies in the methodological
      design of the studies, all articles scored above the acceptable level in terms of
      quality. A majority of the studies revealed that lower extremity amputees have
      increased postural sway in the standing posture. Asymmetry in body weight, which
      is mainly distributed in the non-amputated leg, was described. Aside from the
      centre of pressure in postural control, sensory inputs may be a related topic for
      investigation in view of evidence on their contribution, particularly visual
      input. Other balance-related factors, such as stump length and patients'
      confidence level, were also neglected. Further research requires examination on
      the potential factors that affect postural control as the information of standing
      postural is still limited. 

PMID- 24331298
TI  - Detection of Toxoplasma gondii in shellfish and fish in parts of China.
AB  - In this study, a total of 3432 aquatic animals covering eight species were tested
      by specific polymerase chain reaction (PCR) assays to investigate the presence of
      Toxoplasma gondii, in China. The results showed that, out of 618 Procambarus
      clarkii samples collected from the different areas in southeast China, four
      samples from Jiangxi province were positive. Of 456 Hypophthalmichthys molitrix
      samples, one sample from Jiangsu province was positive. In addition, there was
      only one positive sample collected from Shandong province out of 813
      Macrobranchium nipponense samples. All other samples, including 309 Cyprinus
      carpio, 398 Concha Ostreae, 98 Momopterus albus, 426 Penaeus monodon Fabricius
      and 309 Carassius auratus were negative. The results suggested that the level of
      T. gondii in aquatic animals was low in China. However, the importance of T.
      gondii in aquatic animals should not be ignored. Consumption of contaminated raw
      shellfish may represent a considerable health threat.

PMID- 24331299
TI  - Prevalence of DSM-IV mental disorders, deliberate self-harm and suicidal ideation
      in early adolescence: an Irish population-based study.
AB  - BACKGROUND: This study investigated the prevalence of DSM-IV Axis 1 mental
      disorders, deliberate self-harm and suicidal ideation in a sample of Irish
      adolescents aged 11-13 years. METHODS: A total of 1131 students was surveyed for
      general psychopathology using the Strengths and Difficulties Questionnaire.
      Following this, a representative sample of 212 adolescents was assessed for
      mental disorders, deliberate self-harm and suicidal ideation using the Schedule
      for Affective Disorders and Schizophrenia for School-Aged Children. RESULTS:
      14.6% of the sample met criteria for a borderline score and 6.9% for an abnormal
      score on the Strengths and Difficulties Questionnaire. Following clinical
      diagnostic interviews, 27.4% of participants received a current diagnosis of an
      Axis 1 disorder and 36.8% received a lifetime diagnosis, those rates falling to
      15.4% and 31.2% respectively when specific phobias were excluded. CONCLUSIONS:
      Findings from this study reveal that Irish adolescents aged 11-13 years are
      experiencing high levels of mental ill-health.

PMID- 24331300
TI  - Adolescent peer aggression and its association with mental health and substance
      use in an Australian cohort.
AB  - Prospective longitudinal birth cohort data was used to examine the association
      between peer aggression at 14 years and mental health and substance use at 17
      years. A sample of 1590 participants from the Western Australian Pregnancy Cohort
      (Raine) study were divided into mutually exclusive categories (victims,
      perpetrators, victim-perpetrators and uninvolved). Involvement in any type of
      peer aggression as a victim (10.1%), perpetrator (21.4%), or a victim-perpetrator
      (8.7%) was reported by 40.2% of participants. After adjusting for confounding
      factors, those who were a victim of peer aggression had increased odds of later
      depression and internalising symptoms whilst perpetrators of peer aggression were
      found to be at increased risk of depression and harmful alcohol use. Victim
      perpetrators of peer aggression were more likely to have externalising behaviours
      at 17 years. These results show an independent temporal relationship between peer
      aggression and later mental health and substance use problems in adolescence. 

PMID- 24331301
TI  - Emotional variability during mother-adolescent conflict interactions:
      longitudinal links to adolescent disclosure and maternal control.
AB  - The aim of this study was to examine relations of emotional variability during
      mother-adolescent conflict interactions in early adolescence with adolescent
      disclosure and maternal control in early and late adolescence. Data were used
      from 92 mother-adolescent dyads (M age T1 = 13.05; 65.20% boys) that were
      videotaped at T1 while discussing a conflict. Emotional variability was derived
      from these conflict interactions. Mothers also completed questionnaires at the
      start of the study (T1) and five years later (T6) on adolescent disclosure and
      maternal control. Path analysis showed that more emotional variability during
      conflict interactions in early adolescence was associated with higher levels of
      adolescent disclosure in early adolescence and with relative decreases in
      maternal control from early to late adolescence. More emotional variability of
      mother-adolescent dyads serves an important function in adaptively dealing with
      relational challenges that arise during adolescence. 

PMID- 24331302
TI  - Brief report: Teen sexting and psychosocial health.
AB  - The current study examines whether adolescents who report sexting exhibit more
      psychosocial health problems, compared to their non-sexting counterparts.
      Participants included 937 ethnically diverse male and female adolescents
      recruited and assessed from multiple high schools in southeast Texas. Measures
      included self-report of sexting, impulsivity, alcohol and drug use, and
      depression and anxiety symptoms. Teen sexting was significantly associated with
      symptoms of depression, impulsivity, and substance use. When adjusted for prior
      sexual behavior, age, gender, race/ethnicity, and parent education, sexting was
      only related to impulsivity and substance use. While teen sexting appears to
      correlate with impulsive and high-risk behaviors (substance use), we did not find
      sexting to be a marker of mental health. 

PMID- 24331303
TI  - Feasibility and validity of ecological momentary assessment in adolescents with
      high-functioning autism and Asperger's disorder.
AB  - Ecological Momentary Assessment (EMA) may increase accuracy of data compared with
      retrospective questionnaires by assessing behaviours as they occur, hence
      decreasing recall biases and increasing ecological validity. This study examined
      the feasibility and concurrent validity of an EMA tool for adolescents with High
      Functioning Autism Spectrum Disorders (HFASD). Thirty-one adolescents with HFASD
      completed a mobile phone EMA application that assessed stressors and coping for
      two weeks. Parents and adolescents also completed retrospective measures of the
      adolescent's coping/stressors. Moderate compliance with the EMA tool was achieved
      and some concurrent validity was established with the retrospective measure of
      coping. Concordance was found between the types of stressors reported by parents
      and adolescents but not the quantity. The results suggest adolescents with HFASD
      are capable of reporting on their stressors and coping via EMA. EMA has the
      potential to be a valuable research tool in this population. 

PMID- 24331304
TI  - Brief report: Self-blame and PTSD symptoms in adolescents exposed to terrorism:
      is school connectedness a mediator?
AB  - Previous research has shown that self-blame predicts increased risk of
      posttraumatic stress disorder (PTSD) in youth exposed to terrorism, but little is
      known about the factors mediating such relationship. This study aimed to explore
      whether school connectedness (SC) mediates the effect of self-blame on PTSD in 60
      adolescents (aged 14-18 years) who survived the 2004 terrorist attack against
      school no. 1 in Beslan, Russia. Participants completed measures of coping, SC,
      and PTSD three years after the traumatic event. Endorsement of self-blaming
      behaviors was found to be significantly positively related to the presence of
      PTSD; self-blame was negatively associated with SC, which in turn was negatively
      related to PTSD. The mediation hypothesis was supported, with SC partially
      mediating the link between self-blame and PTSD. Adolescents affected by terrorism
      may benefit from school-based interventions aimed at fostering students' sense of
      belonging and emotional bonding to teachers, peers, and the school environment. 

PMID- 24331305
TI  - Role-modeling and conversations about giving in the socialization of adolescent
      charitable giving and volunteering.
AB  - This study investigated the relationship between the monetary giving and
      volunteering behavior of adolescents and the role-modeling and conversations
      about giving provided by their parents. The participants are a large nationally
      representative sample of 12-18 year-olds from the Panel Study of Income Dynamics'
      Child Development Supplement (n = 1244). Adolescents reported whether they gave
      money and whether they volunteered. In a separate interview parents reported
      whether they talked to their adolescent about giving. In a third interview,
      parents reported whether they gave money and volunteered. The results show that
      both role-modeling and conversations about giving are strongly related to
      adolescents' giving and volunteering. Knowing that both role-modeling and
      conversation are strongly related to adolescents' giving and volunteering
      suggests an often over-looked way for practitioners and policy-makers to nurture
      giving and volunteering among adults: start earlier, during adolescence, by
      guiding parents in their role-modeling of, and conversations about, charitable
      giving and volunteering.

PMID- 24331306
TI  - Brief report: Associations between adolescent girls' social-emotional
      intelligence and violence perpetration.
AB  - This study examined associations between social-emotional intelligence (SEI) and
      two measures of violence perpetration (relational aggression and physical
      violence) in a cross-sectional sample of high-risk adolescent girls (N = 253). We
      evaluated three aspects of SEI: stress management, intrapersonal, and
      interpersonal skills. Results of a multiple linear regression model accounting
      for participants' age, race/ethnicity, and experiences of relational aggression
      victimization indicated that girls with better stress management skills were less
      likely to perpetrate relational aggression. A parallel model for perpetration of
      physical violence showed a similar pattern of results. Study findings suggest
      that SEI, and stress management skills in particular, may protect adolescent
      girls - including those who have been victims of violence - from perpetrating
      relational aggression and physical violence. Interventions that build adolescent
      girls' social and emotional skills may be an effective strategy for reducing
      their perpetration of violence.

PMID- 24331307
TI  - Toward understanding the role of body dissatisfaction in the gender differences
      in depressive symptoms and disordered eating: a longitudinal study during
      adolescence.
AB  - This study was aimed at examining whether body dissatisfaction in early
      adolescence contributes to the development of gender differences in depressive
      symptoms and disordered eating across early to mid-adolescence, testing both a
      mediation hypothesis (higher levels of body dissatisfaction in girls, provided
      body dissatisfaction is a predictor of psychopathology beyond the effect of
      gender) and a moderation hypothesis (more detrimental effect of body
      dissatisfaction in girls). A community-based sample initially comprising 882
      (49.55% female) adolescents (M(age) = 12.85) was followed-up after 2 and 4 years.
      Multilevel models were used to analyze the data. Results supported the mediation
      hypothesis for depressive symptoms and disordered eating, and the moderation
      hypothesis for disordered eating. Whereas gender differences in depressive
      symptoms may be simply linked to dissimilar levels of body dissatisfaction in
      girls and boys, gender differences in disordered eating may arise from both
      dissimilar levels and effects of body dissatisfaction for each gender.

PMID- 24331308
TI  - The effects of out-of-school time on changes in youth risk of obesity across the
      adolescent years.
AB  - This study examined the longitudinal effects of out-of-school time (OST)
      activities on youth weight-status through mid-to-late adolescence. First, using
      pattern-centered methods, we identified the prominent ways in which youth
      allocate their OST across 12 common active and sedentary activities available to
      them. Second, through multi-level modeling procedures we examined the relation of
      OST activity patterns to: 1) BMI-status during the 11th grade, and; 2) within
      person change in BMI-status across the adolescent years. After accounting for
      race, gender, SES, pubertal-status, and gaming, youth who participated in a
      sports-dominant activity pattern for 2 or more years had significantly lower 11th
      grade odds of being at-risk for overweight/obesity compared to youth in all other
      activity patterns. Youth of all other activity patterns had similar odds of being
      at-risk as Low-Activity youth and each other. Understanding the relations of OST
      to youth healthy weight is a critical first step in developing healthy OST
      settings. 

PMID- 24331309
TI  - A differential intra-operative molecular biological test for the detection of
      sentinel lymph node metastases in breast carcinoma. An extended experience from
      the first U.K. centre routinely offering the service in clinical practice.
AB  - INTRODUCTION: One-Step Nucleic acid Amplification (OSNA) is a molecular
      biological assay of cytokeratin-19 (a breast epithelial marker) mRNA. It can be
      employed intra-operatively for detection of lymph node metastases in breast
      carcinoma. Patients with positive sentinel nodes may proceed to axillary lymph
      node dissection (ALND) level I or higher dependent upon the OSNA quantitative
      result, during the same surgical procedure, avoiding a second operation and
      eliminating the technical difficulties possibly associated with delayed ALND.
      AIMS: Our Breast Unit was the first in the UK to implement this novel technique
      in routine practice. This study reviews our first 44-month data following
      introduction of OSNA "live" on whole sentinel nodes following an extensive
      validation study (Snook et al.).(9) METHODS: Data was collected prospectively
      from the period of introduction 01/12/2008 to 30/08/2012. All patients eligible
      for sentinel node biopsy were offered OSNA and operations were performed by five
      consultant breast surgeons. On detection of macro-metastasis a level II/III and
      for a micro-metastasis a level I ALND was performed. RESULTS: A total of 859
      patients (1709 sentinel lymph nodes) were analysed. All except one were females.
      The majority underwent wide local excision (73.4%, n = 631) or mastectomy 25% (n
      = 215) and 1.6% (13) underwent SLN biopsy alone. IDC was seen in 79% (n = 680) of
      the patients and 53.5% (n = 460) had grade II tumours. One-third (30.8%, n = 265)
      had positive sentinel nodes and had further axillary surgery at the time of SLN
      biopsy. Of these, 47% (n = 125/265) had macro-metastases, 38% (n = 101/265) had
      micro-metastases and 14.7% (n = 39/265) had "positive but inhibited" results.
      Positive non-sentinel lymph nodes (NSLN) were seen in 35% (44/125) of those with
      macro-metastases; 17.8% (18/101) of the patients with micro-metastases and 10.2%
      (4/39) of the "positive but inhibited" group. CONCLUSION: In our series over a
      third of our patients had positive lymph nodes detected with OSNA allowing them
      to proceed directly to axillary surgery at the same operation. This technique
      eliminates the need for a second operation in sentinel lymph node positive
      patients and avoids the anxiety waiting for histological results.

PMID- 24331310
TI  - Surgical virtual reality - highlights in developing a high performance surgical
      haptic device.
AB  - Just like simulators are a standard in aviation and aerospace sciences, we expect
      for surgical simulators to soon become a standard in medical applications. These
      will correctly instruct future doctors in surgical techniques without there being
      a need for hands on patient instruction. Using virtual reality by digitally
      transposing surgical procedures changes surgery in are volutionary manner by
      offering possibilities for implementing new, much more efficient, learning
      methods, by allowing the practice of new surgical techniques and by improving
      surgeon abilities and skills. Perfecting haptic devices has opened the door to a
      series of opportunities in the fields of research,industry, nuclear science and
      medicine. Concepts purely theoretical at first, such as telerobotics,
      telepresence or telerepresentation,have become a practical reality as calculus
      techniques, telecommunications and haptic devices evolved,virtual reality taking
      a new leap. In the field of surgery barrier sand controversies still remain,
      regarding implementation and generalization of surgical virtual simulators. These
      obstacles remain connected to the high costs of this yet fully sufficiently
      developed technology, especially in the domain of haptic devices.

PMID- 24331311
TI  - The influence of the analgesic model on postoperative pain in major knee surgery.
AB  - Total primary knee arthroplasty represents a model of severe pain for major
      orthopedic surgery. A good management of postoperative pain is important both for
      the patient and for a good functional surgery outcome because early knee
      mobilisation is pain limited. This study is a review of the main analgesic
      methods used in total primary knee arthroplasty and their influence on pain and
      on the functional recovery of the knee.The comparative analysis of the analgesic
      models shows the advantages and the adverse effects of each one, the evolution in
      time of analgesia techniques and guides us in the use of evidence-based-medicine
      Which is the most appropriate analgesic model is a choice of the orthopedic
      surgeon anesthesiologist and kineto therapist team who are able to individualize
      for each patient good functional outcome parameters of the new knee joint.

PMID- 24331312
TI  - Indication for transplantation in a patient with univentricular heart.
AB  - Surgical correction of the univentrivular heart is an achievement of the last 4-5
      decades. The Fontan pathway is nowadays an established but continuously improving
      surgical technique.Nevertheless, attrition of the univentricular heart is a well
      known process, its timing depending on several factors:technique, time of
      operation, type of ventricle aso. The study group is represented by 39 patients
      with univentricular circulation, operated (37 partial-PCPC and 2 total - TCPC
      cavo-pulmonary anastomosis) in our clinic between 2006 -2012. Out of this group,
      2 patients have reached the stage of indication for heart transplantation: 1 has
      already been transplanted and one is listed for transplantation. The indication
      was in both a failing ventricle of left-type univentricular heart,in a PCPC
      status, performed after 14 years of age. Evolution in the transplanted patient is
      good. In conclusion, the option of heart transplantation should be available and
      kept in mind for the operated univentricular heart even at pediatric ages, as
      local peculiarities cause these hearts to fail even earlier than described in the
      literature.

PMID- 24331313
TI  - Minimally invasive treatment of cholecysto-choledochal lithiasis - "Rendez-vous"
      technique.
AB  - INTRODUCTION: In our paper we present the results of a study that was meant to
      provide a complex answer to the question:"Which is the most appropriate, most
      correct and least expensive treatment for mixt cholecysto-choledochal
      lithiasis(MCCL)?" MATERIAL AND METHODS: Based on a five year experience (2008
      2012), analysed retrospectively, during which 143 patients with MCCL were
      treated, we are trying to find answers to some of the questions that we have
      asked ourselves from the very beginning of this period. The answers were guided
      by alternative therapeutic options, for a pathology that does not have a "gold
      standard", with respect to the solutions available. RESULTS: Given the fact that
      the period during which the study was conducted was chosen randomly and that the
      patients were included consecutively, the representativeness of the results is
      ensured for any other patient diagnosed with this pathology and admitted to a
      clinic with the same specialty, dimensions and equipment as the one presented.
      CONCLUSIONS: This paper compares the results of our study to those of others, in
      terms of different or similar approach therapeutic options, developed in other
      minimally invasive surgery centres in the world, the final conclusions being
      encouraging for the therapeutic sequence that we practice.

PMID- 24331314
TI  - Transthoracic versus Transhiatal esophagectomy: a permanent dilemma. our 15-year
      experience.
AB  - OBJECTIVE: Controversy still exists regarding the optimal surgical management of
      esophageal cancer. This study was performed to determine and compare early and
      late morbidity,mortality and overall survival after transthoracic (TTE) and
      transhiatal esophagectomies (THE). METHODS: Between 1997-2011, 100 patients
      underwent TTE or THE for squamous esophageal carcinoma (90 patients)and
      adenocarcinoma (10 patients). Assessed parameters included patient demographics,
      operative data, pathology results, postoperative morbidity and mortality and 1-3
      year survival. RESULTS: Thoracic approach was preferred in cases of more advanced
      tumors, located in the upper and mid-third of the esophagus, in patients with a
      better cardiopulmonary status. Perioperative blood loss was significantly higher
      after transthoracic resections (p=0.0004) and these surgeries took significantly
      longer than transhiatal esophagectomies(p=0.02). We identified complications in
      70.7% patients who under went TTE and in 59.3% patients with transhiatal
      approach. Respiratory complications were statistically significant in the TTE-
      group (p-0.0003). The 30-day mortality rates were 12.2% for patients in TTE group
      and 10.1% in THE patients group, respectively. The mortality ratefor the entire
      period of the study has been calculated at 84.4%.We have identified a survival
      rate after 1 year of 62.2%, after 2 years of 39.3% and after 3 years - 15.1%.
      CONCLUSIONS: According to the results of this study, both procedures appear to be
      acceptable depending on surgeon preference and appropriate patient selection.

PMID- 24331315
TI  - Quality of life after laparoscopic fundoplication for gastroesophageal reflux
      disease. Preliminary study.
AB  - Laparoscopic fundoplication (LF) is the treatment of choice for gastroesophageal
      reflux disease (GERD).Our paper evaluates post LF quality of life (QL). Patients
      treated between January 2008 and May 2011 by the same surgeon were asked to fill
      in the Velanovich questionnaires for Gastro - Oesophageal Reflux Disease - Health
      Related Quality of Life (GERD-HRQL). The 10 questions were designed to assess
      GERD specific symptoms prior to (part A) and after surgery (part B). The
      Velanovich score is 0 if the patient is asymptomatic and 50 if the symptoms are
      at maximum intensity. Only 32 out of the 54 patients operated during the study
      filled in the questionnaire:28 patients (87.5%) had hiatus hernia (HH), 16 cases
      were associated with reflux erosive esophagitis (EE), 4 patients had non-erosive
      reflux disease (NERD) and one had Barrett's esophagus (BE). We used Toupet
      partial posterior fund oplication for 12 patients and Nissen total fundoplication
      for 20 patients. The short gastric vessels were divided in all patients.The
      female - male ratio was 21:11 with a mean age of 55.13 years and the mean follow
      up period for questionnaire B was of25.2 months. The Velanovich A score was 29.9
      A+-10.9, and the follow up B score was 3.4A+-2.4 (CI (95%) 22.9-39.9; p
      0.05).There were no B score statistical differences between sex ratio(3.9 vs 2.4)
      and type of fundoplication (Nissen 3.2 vs Toupet4.1). 29 patients (90.62%)
      declared that their QL improved after surgery. The main indication for surgery
      present in almost every patient included in this study was the presence of theHH
      and RE. LF improved the quality of life of patients with GERD. There were no
      statistical differences of the Velanovich score according to GERD stage (EE, NERD
      with or without HH), sex ratio and type of LF, Toupet or Nissen.

PMID- 24331316
TI  - The surgical treatment of chronic pancreatitis: a clinical series of 17 cases.
AB  - INTRODUCTION: Despite the fact that in the last few years, new invasive non
      surgical therapies were introduced, surgical treatment of chronic pancreatitis
      still plays an important part.The aim of the study is to evaluate pain remission
      and quality of life after surgical approach. MATERIAL AND METHOD: We present 17
      cases of chronic pancreatitis that were operated between 2007-2011. Surgical
      treatment was decided for after the failure of pain control therapy (14 cases)and
      by the suspicion of cancer in the head of the pancreas (3 cases). Imaging data
      for all the cases, CT-CE and ERCP, guided us in choosing the right therapy.
      Surgical techniques performed were pancreatico-jejunostomy (PJ) in eleven cases
      and duodenopancreatectomy(DP) in six cases. RESULTS: Good pain control was
      achieved in 10 patients: 6-PJ and 4-DP. Moderate results were observed in 4
      cases: 2-PJ and 2-DP. In 3 patients symptoms remained the same. CONCLUSION: There
      is no consensus over the surgical treatment in chronic pancreatitis. Surgical
      approach, strongly motivated and personalised for each patient is followed by
      good results. It is possible that in the future, limited resections become the
      therapy of choice, replacing classic ones.

PMID- 24331317
TI  - Cryosurgery for isolated liver tumors or associated with complex liver resection:
      a series of 38 patients.
AB  - BACKGROUND: The aim of this prospective study is to assess the outcomes of
      cryosurgery for liver tumors, as a single treatment or associated to liver
      resections in conjunction or not with other visceral resections. MATERIAL AND
      METHODS: Between 2001 and 2011, in our institution,70 hepatic tumors have been
      treated through cryo surgery in 38 patients. Complications and survival were
      assessed,according to different types of hepatic tumors and treatment complexity.
      RESULTS: Operative mortality within 1 month was 2.6% related to cryosurgery. The
      median follow up was 25.8 months (range from 0-41.85 months). The number of
      complications was associated to complex treatment. The morbidity,
      mortality,disease-free and overall survival rates were not statistically
      significantly different between the different types of tumors (p value 0.05). The
      median disease free survival was 9.5 months, with cryosite recurrent disease in
      21.5% patients, and 28.9% recurrences in other liver sites. CONCLUSION:
      Cryotherapy, single or associated with liver resections combined or not with
      other visceral resections is an effective procedure. The antitumoral effects of
      treatment were demonstrated, but complications and high local recurrence rate,
      especially in patients with extensive disease, should caution against its use.

PMID- 24331318
TI  - Association of ventral incisional hernias with comorbid diseases.
AB  - BACKGROUND: Ventral incisional hernias are more commonly associated with comorbid
      diseases when compared to other hernia types. We investigate the hypothesis that
      unfavourable local factors related to comorbid diseases may lead to incisional
      hernia development. MATERIALS AND METHODS: The characteristics of incisional
      hernia (71 patients), primary ventral hernia (114 patients)and groin hernia
      groups (820 patients) were analysed and compared among each other. RESULTS:
      Advanced age, female gender, presence of coexisting disease, strangulation,
      incarceration, bowel or omentum resections, deep venous thrombosis, ileus, wound
      infections,ASA scores were significantly higher and the duration of hospital stay
      was longer in the incisional hernia group when compared to the other groups.
      Presence of coexisting diseases and ASA class scores were independent predictors
      of length of hospital stay in incisional hernia patients (p 0.05). CONCLUSIONS:
      Ventral incisional hernias are associated with higher incidence of comorbid
      diseases in comparison with other types of abdominal wall hernias. Patients with
      coexisting diseases might have unfavourable local factors that lead to incisional
      hernia development.

PMID- 24331319
TI  - Surgical outcome of inflammatory bowel disease - experience of a tertiary center.
AB  - BACKGROUNDS/AIM: Despite advances in medical treatment, a large number of
      patients with inflammatory bowel disease(IBD) require surgery. We aim to evaluate
      the efficacy and outcome of surgical interventions in patients with chronic
      inflammatory bowel diseases. MATERIAL AND METHODS: We retrospectively analysed
      the medical records from 221 patients admitted to our institution between 2009
      2012 with the diagnosis of IBD. Out of these patients, 55 (24.88 %) were
      diagnosed with Crohn's disease,while the remaining 166 patients (75.11%) had
      ulcerative colitis. RESULTS: Seventeen of 55 patients with Crohn's disease
      (30.91%)required surgical management before or during this period. Nine with
      disease proximal to the transverse colon underwent segmental resections (enteral
      or colonic) with primary anastomosis, without morbidity. The other 8 patients,
      with disease distal to the transverse colon, underwent segmental colonic
      resections (two with primary anastomosis, three with stoma formation) or major
      colonic resection- subtotal colectomy with ileostomy (1 case) and total
      proctocolectomy with ileostomy(2 cases). Sixteen of 166 patients with ulcerative
      colitis(9.64%) required surgery before or during this period. The surgical
      procedure used included total proctocolectomy with definitive ileostomy (3 cases)
      and total colectomy with ileostomy(13 cases). 7 of the 13 patients had
      restorative surgery after total colectomy, 1 remaining with definitive ileostomy
      due to short vascular pedicle and 5 patients refused restorative surgery. Median
      daily stool frequency after reconstructive surgery was 7(range 3-12). CONCLUSION:
      For patients with Crohn's disease proximal to the transverse colon, limited
      resection with primary anastomosis is safe. Major colonic resection (subtotal
      colectomy or proctocolectomy)is indicated if the disease is located distal to the
      transverse colon and primary anastomosis should be avoided. Due to unsatisfactory
      quality of live after reconstructive surgery(stool frequency remains high), total
      proctocolectomy with end-ileostomy remains a viable alternative for patients with
      ulcerative colitis.

PMID- 24331321
TI  - Pre-operative hypoalbuminemia in colorectal cancer patients undergoing elective
      surgery - a major risk factor for postoperative outcome.
AB  - BACKGROUND: The incidence of hypoalbuminemia in surgical patients varies in
      different studies with age, tumor stage, time interval to the first referral to a
      doctor, symptoms of disease and nutritional habits of the population. The main
      objective of this study was to evaluate the incidence of hypoalbuminemia in
      colorectal cancer patients undergoing scheduled surgery in an academic hospital
      in Romania and the impact of hypoalbuminemia on perioperative outcome. The
      secondary objective was to identify other possible risk factors for the post
      operative outcome. MATERIAL AND METHODS: 252 patients undergoing scheduled
      colorectal surgery with anastomosis have been enrolled in the study. Incidence of
      hypoalbuminemia (serum albumin 3.5 g dL), fistulas and other postoperative
      complications (e.g.infections) has been evaluated. LOS and 30-days mortality have
      also been evaluated comparatively in patients with normal and low serum albumin.
      RESULTS: 28.9% of our patients were hypoalbuminemic. The incidence of fistulas
      was 5.5 % in the study group and 2.3% and 13.3% in patients with normal serum
      albumin and hypoalbuminemic patients, respectively (p=0.001). Multivariate
      analysis showed that the OR was 6.65 [95% CI:2.01-21.96] inpatients with moderate
      hypoalbuminemia and 24.75 [95% CI:6.75-90.67] in patients with severe
      hypoalbuminemia.Association between alcohol consumption and smoking increased
      risk ratio to 1.96 [95% CI: 0.51-7.46]. CONCLUSION: The high incidence of
      hypoalbuminemia in our patients justifies preoperative nutritional interventions
      and specific surgical protocols in emergency cases. Further studies are needed to
      exactly quantify the impact of smoking and alcohol consumption on postoperative
      outcome.

PMID- 24331320
TI  - Microsatellite instability in the management of stage II colorectal patients.
AB  - BACKGROUND: Up-to-date it is unclear whether stage II colorectal cancer patients
      should receive adjuvant chemotherapy.The presence of high risk features (T4, CEA
      5 ng dl, less than 12 lymph nodes examined) is an indication for Oxaliplatin
      based treatment. In their absence, there is no consensus, 5 Fluorouracil
      regimens, or observation only being equally recommended by oncologists.
      Microsatellite instability is associated with good prognosis in stage II
      colorectal cancer and also with poor response to 5 Fluorouracil and should be
      used as a predictive marker. METHODS: We performed a prospective descriptive
      study on 115 consecutive patients who received surgical resection for colorectal
      cancer in our clinic during 2011 and 2012 using a risk stratification algorithm
      based on TNM staging, clinico pathologic and molecular markers. RESULTS: From the
      44 stage II colorectal cancer patients, 10 cases were classified as high risk, in
      26 cases we performed Immunohistochemical analysis that identified 8 patients
      with low risk microsatellite instability phenotype, with no indication for
      adjuvant chemotherapy; 26 intermediate risk patients received 5-FluoroUracil
      regimens. CONCLUSION: We believe that microsatellite instability testing provides
      a useful tool in the goal of better characterizing patients with stage II
      colorectal cancer in matters of risk of recurrence and likelihood of benefit from
      chemotherapy.

PMID- 24331323
TI  - Hernia mesh repair of the anterior abdominal wall and antibiotic
      chemoprophylaxis: multiple doses of antibiotics failed to prevent or reduce wound
      infection.
AB  - BACKGROUND: Mesh repair of the anterior abdominal wall hernias is a popular
      technique and commonly accepted among the majority of surgeons. The technique
      used most frequently today is the free tension technique. It is uncertain whether
      antibiotic prophylaxis is necessary to prevent post operative wound infection,
      especially when a foreign body like a polypropylene mesh is used. METHODS: We
      have studied retrospectively the patients who received surgical treatment in our
      department for anterior abdominal wall hernia during the period of January 1995 
      December 2004. Patients were divided into 3 groups based on the doses of
      antibiotics administered. RESULTS: In 780 out of 1245 cases, a mesh of
      polypropylene was used. In our sample, we excluded 221 patients due to diseases
      that made the use of antibiotics necessary. We have studied the frequency of
      superficial and deep infections in correlation with the use of antibiotics
      (cephalosporin of second generation or a combination of ampicillin plus
      sulbactam). CONCLUSION: No difference was observed in the incidence of surgical
      trauma infection in relation to the duration and the doses of antibiotic cover.
      The wound infection rate in the current study does not support the use of
      multiple doses of antibiotics, as this rate does not differ from the rates of
      infection reported in the literature. Further studies are needed to clarify if
      antibiotic chemoprophylaxis with one dose or no chemoprophylaxis should be
      recommended.

PMID- 24331322
TI  - The value of serum bilirubin level and of white blood cell count as severity
      markers for acute appendicitis.
AB  - Discussions regarding the correlations between elevated white blood cell levels
      and clinical and pathological stages of acute appendicitis are well known. Recent
      studies show that a high level of serum bilirubin could emerge as a prognostic
      marker for gangrenous or perforated stages of acute appendicitis. We studied the
      correlations between anatomical and pathological stages of acute appendicitis and
      white blood cell count, serum total bilirubin, and indirect serum bilirubin on a
      large series of cases, in the course of one year, in our department. Although
      there being a correlation between severe forms of acute appendicitis (gangrenous,
      perforated), elevated white blood cell count, elevated serum bilirubin (mostly
      the indirect fraction), none of the indicators proved to have a definitive
      diagnostic value. Cases with perforation and localized generalized peritonitis
      are more frequently associated with elevated bilirubin levels.

PMID- 24331324
TI  - Effects of ethylene oxide resterilization and in-vitro degradation on mechanical
      properties of partially absorbable composite hernia meshes.
AB  - BACKGROUND AND AIM: Prosthetic mesh repair for abdominal wall hernias is widely
      used because of its technical simplicity and low hernia recurrence rates. The
      most commonly used material is pure polypropylene mesh, although newer composite
      materials are recommended by some centers due to their advantages.However, these
      meshes are more expensive than pure polypropylene meshes. Resterilization of a
      pure polypropylene mesh has been shown to be quite safe, and many centers prefer
      slicing a large mesh into smaller pieces, suitable for any hernia type or defect
      size. Nevertheless there is no data about the safety after resterilization of the
      composite meshes. The present study was carried out to investigate the effects of
      resterilization and in vitro degradation in phosphate buffered saline solution on
      the physical structure and the mechanical properties of partially absorbable
      lightweight meshes. METHODS: Two composite meshes were used in the study: One
      mesh consists of monofilament polypropylene and monofilament polyglecaprone -a
      copolymer of glycolide and epsilon(epsilon)- caprolactone - (Ultrapro(r), 28 g
      m2, Ethicon, Hamburg,Germany), and the other one consisted of multifilament
      polypropylene and multifilament polyglactine (Vypro II(r), 30g m2, Ethicon,
      Hamburg, Germany). Two large meshes were cut into rectangular specimens sized 50
      x 20 mm for mechanical testing and 20 x 20 mm for in vitro degradation
      experiments.Meshes were divided into control group with no resterilization and
      gas resterilization. Ethylene oxide gas sterilization was performed at 55 degrees
      C for 4.5 hours. In vitro degradation in 0.01M phosphate buffered saline (PBS, pH
      7.4) solution at 37 +/- 1 degrees C for 8 weeks was applied to one subgroup in
      each mesh group. Tensiometric measurements and scanning electronmicroscopic
      evaluations were completed for control and resterilization specimens. RESULTS:
      Regardless of resterilization, when the meshes were exposed to in vitro
      degradation, all mechanical parameters decreased significantly. Highest reduction
      in mechanical properties was observed for Ultrapro due to the degradation of
      absorbable polyglecaprone and polyglactin parts of these meshes. It was observed
      that resterilization by ethylene oxide did not determine significant difference
      on the degradation characteristics and almost similar physical structures were
      observed for resterilized and non-resterilized meshes. For VyproII meshes, no
      significant mechanical difference was observed between resterilized and non
      resterilized meshes after degradation while resterilized Ultrapro meshes
      exhibited stronger characteristics than non-resterilized counterparts, after
      degradation. CONCLUSION: Resterilization with ethylene oxide did not affect the
      mechanical properties of partially absorbable compositemeshes. No important
      surface changes were observed inscanning electron microscopy after
      resterilization.

PMID- 24331325
TI  - The significance of PDGF expression in serum of colorectal carcinoma patients-
      correlation with Duke's classification. Can PDGF become a potential biomarker?
AB  - BACKGROUND: The expression of serum angiogenic factors has been associated with
      tumor dissemination and poor prognosis in multiple cancer types. However, it is
      still unclear whether these angiogenic molecules can be used as an independent
      molecular marker or in correlation with other parameters for predicting the
      prognosis of colorectal carcinoma (CRC)patients. METHODS: Protein expression was
      evaluated in 28 CRC and 10 control cases using Angiogenesis Fast Quant
      technology. RESULTS: In this study, we found downregulation of PDGF-bb protein
      expression in the serum of patients with colorectal cancer compared with the
      control group. Thus, PDGF-bb might play an essential function in the progression
      of CRC. CONCLUSIONS: Our study indicated that the PDGF-bb protein expression
      might be an independent prognostic marker or in association with other parameters
      for CRC patients.

PMID- 24331326
TI  - Is prosthetic repair of the abdominal wall in clean-contaminated surgical
      interventions possible?
AB  - The present study tries to provide an expressive, customized answer to the
      question in the title. The study relies on a ten-year experience (2000-2009),
      evaluated retrospectively on a group of 488 prosthetic repairs of incisional
      herniae, out of which 432 were performed in a clean environment and 56 cases in a
      clean-contaminated one. The two groups are superimposable based on the Apache
      score. The visceral surgical procedures associated to the surgery of the parietal
      defect were varied (cholecystectomy, appendectomy, enterectomy
      enterorrhaphy,colectomy colotomy-colorrhaphy, hysterectomy with adnexectomy). The
      assessment of postoperative suppurative complications showed no significant
      differences between the two groups (p 0.001). These results lead us to the idea
      of defining the indication for parietal prosthetic repair in a contaminated
      environment. The major factors of this decision are: the nature, the source and
      the amount of the septicinoculum, the duration of exposure, the intensity of the
      host inflammatory response (more difficult to quantify), and finally the surgical
      judgment. The last mentioned factor will evaluate the above-mentioned data and
      will take into account that not all bacterial contaminations are necessarily
      followed by an established infection. Thus, additional exaggerations - which
      would mean taking useless, ineffective precautions- as well as negative
      exaggerations - which would mean hazardous boldness- will be avoided.

PMID- 24331327
TI  - Corelation of lymphocytic infiltrates with the prognosis of recurrent colo-rectal
      cancer.
AB  - BACKGROUND: Recent studies are focusing on complementary prognostic and
      predictive markers that could complete the predictive TNM staging and one of the
      most promising directions is the study of tumor immune infiltrates. MATERIALS AND
      METHODS: Our 2-year retrospective study includes resection specimens from the
      primary tumors of 23 patients presenting to our clinic for a local or a distant
      relapse after colon or rectal cancer. From every primary tumor specimen we
      obtained immunohistochemically stained slides in order to assess cd3, cd4, cd8,
      cd45ro and cd68 infiltrates. Digital analysis assessed the density and percentage
      of positively stained cells in the normal peritumoral tissue, invasive margin and
      center of the tumor. RESULTS: A small density of cd8 positive cells in the
      peritumoral region was strongly correlated with a longer disease-free interval
      (p=0.009) and the Kaplan-Meier survival analysis showed that the percentage of
      cd8+ T cells could be used to stratify patients in terms of relapse risk
      (p=0.006). We found no correlation between invasion front infiltrates and intra
      tumoral infiltrates and the disease-free interval. CONCLUSION: Our study
      concludes that cytotoxic T-cell infiltrates in the normal peritumoral tissue
      could be used to predict a more aggressive tumor in terms of the relapse risk.

PMID- 24331328
TI  - Herbert capsuloplasty and Burnei tenomyoplasty for the correction of genu flexum
      in cerebral palsy, arthrogryposis and posttraumatic.
AB  - INTRODUCTION: Studies of gait dynamics revealed the complex motions that the knee
      must undergo in sync with the hip and ankle, in both the swing and support phase
      of walking. If these motions are restricted, usually as a consequence of cerebral
      palsy or arthrogryposis, normal gait is hindered; the patient may be able to walk
      for very short distances or, eventually, not at all. Children with knee extension
      limited by 10 - 30 degrees,especially those with cerebral palsy, exhibit a stance
      compatible with walking. Walking is difficult and the gait pattern, "crouch
      gait", is considered typical for this degree of limitation. AIM: This paper is
      meant as an update regarding the usefulness of Herbert knee capsuloplasty,
      conceived in 1938 and introduced in Romania in 1956 by Clement Baciu, and
      Burneidistal medial hamstring tenomyoplasty, invented in 1993. MATERIALS AND
      METHODS: Herbert knee capsuloplasty, although initially intended for ailments
      other than spasticity or arthrogryposis,became known, in time, as a useful
      operation for spastic genu flexum with a 15 to 30 degree limitation of extension.
      Severing the posterior cruciate ligament (PCL) in children less than 10 years old
      often results in genu recurva tumor joint instability. In order to avoid these
      complications, PCL transection has been phased out and our clinic started to use,
      preferentially for spastic genu flexum rather than arthrogryposis,the Burnei
      tenomyoplasty. When applied in the same operative session, the two techniques
      complement each other and act in synergy. RESULTS: Herbert capsuloplasty can
      achieve only partial correction of genu flexum ranging between 30 and 60 degrees
      of extension deficit. Full extension is opposed by the PCL,contracture of the
      hamstrings and vascular retraction. Burnei tenomyoplasty used by itself is useful
      for genu flexum with less than 30 degrees of extension deficit. For children with
      30 to 60 degrees of knee extension deficit, combining the Herbertand Burnei
      procedures achieves the best results. CONCLUSIONS: The simultaneous application
      of Herbert capsuloplasty and Burnei tenomyoplasty allows for the correction of
      stiff genu flexum and enables the patient to resume walking,with or without
      support. This course of treatment also avoids the progression of genu flexum
      beyond 60 degrees, which would require an osteotomy. This combined procedure
      avoids the cartilage lesions which may develop when patients with 30- 60 degree
      genu flexum undergo Herbert capsuloplasty alone.Not in the least, the risk of
      postoperative knee dislocation is significantly reduced.

PMID- 24331329
TI  - The influence of total knee arthroplasty on postural control.
AB  - INTRODUCTION: The aim of this study is to assess the changes induced by the
      unilateral total knee arthroplasty procedure in human postural control. MATERIALS
      AND METHODS: The measurements were performed using the "AMTI AccuGait" force
      plate. Subjects completed three consecutive double-limb standing balance trials.
      The mediolateral and anteroposterior displacements were derived from the force
      and moment profiles measured by the force platform. The path length per unit time
      (average velocity) and Elipse 95 (collect 95% of data) were also assessed.
      RESULTS: Mediolateral displacement increase of 3.4% was observed postoperatively.
      Postoperative anterolateral displacement increase of 23.2% was recorded. The
      average velocity also rose by 16.8% postoperatively. The Elipse 95 grew by
      33.7%postoperatively. DISCUSSION: Excepting mediolateral displacement, all the
      other studied parameters showed significantly (p 0.05) higher values in the
      postoperative period compared with the preoperative one, in both open and closed
      eye trials. CONCLUSIONS: The study results demonstrate that balance control is
      weaker shortly after unilateral knee arthroplasty,than in the preoperative
      period. Although proprioception is altered in osteoarthritic knees, the TKA
      procedure may additionally affect proprioceptors. The TKA causes additional
      instability in the days after the procedure, therefore the risk of falling
      injuries is higher in this period.

PMID- 24331330
TI  - Results of surgical treatment of acetabular fractures using Kocher-Langenbeck
      approach.
AB  - AIM OF THE STUDY: To evaluate the results of acetabular fractures surgically
      treated using posterior Kocher-Langenbeck approach for internal fixation.
      METHODS: A series of 42 consecutive cases treated during a 4 year period was
      analysed. The mean age of the patients was 41 years. According to the Letournel
      classification 9 posterior wall fractures, 3 posterior column fractures, 11
      transverse fractures,4 posterior column and posterior wall fractures, 10
      transverse and posterior wall fractures and 5 T-shaped fractures were noted.
      RESULTS: Quality of reduction based on Matta's criteria shows anatomical
      reduction in 25 cases (59.5%), imperfect in 11 cases(26.2%) and poor in 6 cases
      (14.3%). Neurological injury represented by peroneal nerve palsies occurred in 3
      patients(7.1%). Acute infection was noted in one case (2.4%). Clinical results
      (for 38 patients) was excellent in 9 cases (23.7%), good in 23 cases (60.5%),
      fair in 4 cases (10.5%) and poor in 2 cases(5.3%). There was a statistically
      significant correlation between quality of reduction and clinical results with r
      = 0.68 (Pearson coefficient). Heterotopic ossifications were recorded in 14 cases
      and osteonecrosis of the femoral head was recorded in 2 cases. CONCLUSIONS:
      Despite the relatively large number of complications,surgery treatment for
      acetabular fractures offers better results than conservative treatment, in which
      the complication rate is much higher.

PMID- 24331331
TI  - Adrenal and pituitary incidentalomas in a case of Cushing's syndrome.
AB  - Cushing's syndrome is a pathological condition where surgery may be lifesaving.
      The proper diagnosis depends upon the hormonal pattern of the patient, various
      dynamic tests and imagistic investigations. We report a case of a patient with
      Cushing's syndrome, with bilateral adrenal tumors and a pituitary microadenoma.
      She presented increased levels of basal cortisol, unsuppressed during a low and a
      high dose Dexamethasone test. She underwent right laparoscopic adrenalectomy and
      developed acute adrenal insufficiency. Two years after the intervention, she
      still requires adrenal substitution therapy. Acute adrenal crisis is a serious
      complication of adrenal surgery, with high mortality if unrecognized.

PMID- 24331332
TI  - Ileo-ceco-descendento-colic intussusception in adult - a case report.
AB  - INTRODUCTION: Intestinal intussusception in adult represents a rare cause of
      intestinal obstruction, therefore the diagnostic and therapeutic methods must be
      adapted to each case. MATERIALS AND METHODS: We present the case of a 30 year old
      female admitted in our service suffering from a subocclusive symptomatology.
      After preoperative tests were completed in another medical unit, we presumed the
      possibility of intestinal intussusception. The intraoperative exploration
      revealed the presence of a terminal ileum tumor (4x5x5 cm) with the invaginated
      segment progressed on ileo-ceco-transversodescendento-colic trajectory. After
      partial desinvagination, we performed right hemicolectomy with ileo-transverse
      end-to-endanastomosis. RESULTS: The patient was discharged healthy on the 7th
      postoperative day. The histopathological findings revealed submucosal ileal
      lipoma. CONCLUSIONS: Tumors of the terminal ileum, cecum or right colon could
      have an important role in the etiology of mechanical intestinal obstructions.
      These tumors can be a starting point for intestinal intussusception, which can
      advance to the left colon.

PMID- 24331333
TI  - A rare case of acute abdomen: Garengeot hernia.
AB  - The association of acute appendicitis with femoral hernia,strangulated or
      incarcerated, represents a rare but well documented pathology in the specialized
      medical literature,also known as Garengeot hernia. The development of an acute
      appendicitis in the femoral hernia sac becomes a surgical emergency of acute
      abdomen. The diagnosis is always mistaken for the one of incarcerated or
      strangled hernia, the correct diagnosis being established intraoperatively,
      occasion which exposes the cecal appendix by opening the herniary bag, found in
      different morphological stages of inflammation that can go as far as gangrene or
      even perforation. In this paper, we have reported the case of a 76 year-old
      female that presented with femoral tumours, incarcerated, painful and initially
      considered as an incarcerated femoral hernia, the final diagnosis being made
      intraoperatively. The treatment for these "hernias" is generally simple, when
      there are no complications of acute appendicitis as the presence of pus in the
      hernia sac, and consists in appendectomy and herniorrhaphy. The absence of
      symptoms for an acute appendicitis often delays the surgery which leads to
      frequent complications and increased rate of morbidity.

PMID- 24331334
TI  - Multiple endocrine neoplasia type 2A: case report.
AB  - Multiple endocrine neoplasia type 2A (MEN 2A) is a complex autosomal dominant
      inherited syndrome characterized by medullary thyroid carcinoma (MTC),
      pheochromocytoma and primary parathyroid hyperplasia. In patients with only one
      or two clinical features, identification of a germline RET(REarranged in
      Transfection) mutation or the identification of the clinical features of MEN 2A
      in other first degree relatives is required to make the diagnosis. We present the
      case of a family with MEN 2A syndrome confirmed by genetic analysis which
      identified RET gene mutation in 634 codon in father - DV - aged 48 years and also
      in daughter DM -aged 20 years. The specific feature in this case is that the
      index case was the daughter (diagnosed and operated for pheochromocytoma at the
      age of 19 years), the father being diagnosed later with medullary thyroid
      carcinoma by mutational screening in all family members. This family supports the
      phenomenon of anticipation, in which severity increases and the age of onset
      decreases in successive generations, the syndrome being discovered earlier and
      with a worse prognostic in the daughter.

PMID- 24331335
TI  - A case of respiratory epithelial adenomatoid hamartoma.
AB  - We report a case of a 50-year-old man diagnosed with a unilateral nasal mass
      found to be a respiratory epithelial adenomatoid hamartoma (REAH) upon pathologic
      examination.REAH is a recently described pathologic entity that can present with
      nasal obstruction, congestion, rhinorrhoea,epistaxis, hyposmia, and headaches. It
      is a rare lesion of nasal and paranasal sinuses, but should be considered in the
      differential diagnosis because it is a benign lesion and complete surgical
      resection is curative.

PMID- 24331336
TI  - Unusual anatomical detection of a third molar in the infratemporal fossa.
AB  - Third molar presence in the infratemporal fossa is a rare event and it has been
      reported previously only two times in the literature, except for the cases which
      arise from complications occurring during the extraction of the impacted upper
      third molar. Due to the presence of important vessel bundles and nerves in this
      area, third molar removal requires a correct surgical management in order to
      avoid many possible serious side effects. We report an unusual case of upper
      third molar detected in the infratemporal fossa, which has been thoroughly
      investigated radiologically and removed through a safe surgical approach.

PMID- 24331337
TI  - Emergency pancreaticoduodenectomy for bleeding pancreatic pseudoaneurysm in
      patient with common mesentery and replaced right hepatic artery.
AB  - Pancreaticoduodenectomy is infrequently performed in emergency, so much the less
      in lack of traumatic evidence.A rare vascular complication of the pancreatic
      pseudocyst,the pseudoaneurysm, presents as a pulsating malformation which may
      lead to life-threatening bleeding if left untreated.Its optimal treatment remains
      controversial. Most authors agree that angioembolization is the first step to
      stabilize the patient's condition, with further surgery if such be the case.We
      herein report an unusual case of pancreatic head pseudocyst complicated with a
      bleeding pseudoaneurysm arising from the inferior pancreaticoduodenal artery, in
      a patient with multiple comorbid conditions, common mesentery,hepatic artery
      variant and hemodynamic instability. An emergency early retropancreatic approach
      pancreaticoduodenectomy was performed with uneventful immediate and long-term
      outcome. We highlight that emergency surgery allowed both rapid control over the
      bleeding with hemostasis and removal of the pseudocyst. This is particularly
      relevant in high-risk patients in whom selective angioembolization is no more of
      choice.

PMID- 24331338
TI  - Cost and outcomes matter.

PMID- 24331339
TI  - Legends in urology.

PMID- 24331340
TI  - MRI characterization of the dynamic effects of 5alpha-reductase inhibitors on
      prostate zonal volumes.
AB  - INTRODUCTION: Prior studies of volumetric effects of 5alpha-reductase inhibitors
      (5ARIs) on the prostate have used transrectal ultrasound which provides poor
      differentiation of prostatic zones. We utilized high-resolution prostate MRI to
      evaluate the true dynamic effects of 5ARI in men who underwent multiple MRIs.
      MATERIALS AND METHODS: A retrospective study of patients who underwent serial 3.0
      Tesla prostate MRI from 2007 to 2012 and were treated with 5ARI were studied.
      Nineteen patients who had a baseline MRI prior to 5ARI initiation and subsequent
      MRI follow up were selected. A randomly selected group of 40 patients who had not
      received any form of therapy was selected as the control cohort. Total prostate
      volume (TPV), transition zone volume (TZV), and peripheral zone volume (PZV) were
      calculated using 3D reconstructions and prostate segmentation from T2-weighted
      MRI. Changes in volumes were correlated with the duration of treatment using
      linear regression analysis. RESULTS: Following over 2 years of treatment, 5ARI
      decreased TPV significantly (16.7%, p < 0.0001). There were similar decreases in
      TZV (7.5%, p < 0.001) and PZV (27.4%, p = 0.0002) from baseline. In the control
      group, TPV and TZV increased (p < 0.0001) while PZV remained stable. When
      adjusted for the natural growth of prostate zonal volume dynamics seen in the
      control cohort, approximately 60% of the reduction of the TPV from 5ARI resulted
      from changes in the TZV and 40% of the reduction from changes in the PZV.
      CONCLUSIONS: 3.0 Tesla MRI characterizations of the dynamic effects of 5ARI on
      prostate zonal volumes demonstrate significant decreases in TPV, TZV, and PZV.
      5ARI blocks the natural growth of TZV as men age and decreases both TZV and PZV
      below their baselines. As imaging technology improves, prostate MRI allows for
      more accurate assessment of drug effects on dynamic prostate volumes.

PMID- 24331341
TI  - Effect of metastatic site on emergency department disposition in men with
      metastatic prostate cancer.
AB  - INTRODUCTION: Though the prevalence of metastatic prostate cancer is decreasing,
      the rate of admission from the emergency department (ED) is increasing. Little is
      known about the implications of metastatic site on a patient's ED course and
      admission. MATERIALS AND METHODS: A weighted estimate of 15,367 patients with
      metastatic prostate cancer who presented to the ED between January 1, 2006 and
      December 31, 2009 was abstracted from the Nationwide Emergency Department Sample
      (NEDS). Descriptive statistics were used to elaborate patient and hospital
      characteristics of the metastatic prostate cancer population and logistic
      regression models were fitted to identify predictors of admission. RESULTS: The
      most common site of metastasis in patients with metastatic prostate cancer
      presenting to the ED was bone (80.6%), followed by liver (13.2%), lung (9.3) and
      other genitourinary sites (8.1%). Over the study period, there was an increase in
      prevalence of the four commonest metastatic sites, and admission rates varied
      between metastatic sites (83.2% for bone to 95.2% for nodal metastasis).
      Substantial variability in the rate of inpatient mortality was noted. Increasing
      age, Northeast region, increased comorbidity burden, and the presence of nodal
      metastases and other urinary metastases were shown to be independent predictors
      of hospital admission. CONCLUSIONS: The commonest metastatic site in patients
      presenting to United States EDs with metastatic prostate cancer between 2006 and
      2009 was bone. Patients presenting with nodal metastases were most likely to be
      admitted. Independent predictors of hospitalization included age, Northeast
      region, increased comorbidities, nodal metastases and other urinary metastases.

PMID- 24331342
TI  - Proton therapy for prostate cancer online: patient education or marketing?
AB  - INTRODUCTION: Proton therapy (PT) for prostate cancer is an expensive treatment
      with limited evidence of benefit over conventional radiotherapy. We sought to
      study whether online information on PT for prostate cancer was balanced and
      whether the website source influenced the content presented. MATERIALS AND
      METHODS: We applied a systematic search process to identify 270 weblinks
      associated with PT for prostate cancer, categorized the websites by source, and
      filtered the results to 50 websites using predetermined criteria. We then used a
      customized version of the DISCERN instrument, a validated tool for assessing the
      quality of consumer health information, to evaluate the remaining websites for
      balance of content and description of risks, benefits and uncertainty. RESULTS:
      Depending on the search engine and key word used, proton center websites (PCWs)
      made up 10%-47% of the first 30 encountered links. In comparison, websites from
      academic and nonacademic medical centers without ownership stake in proton
      centers appeared much less frequently as a search result (0%-3%). PCWs scored
      lower on DISCERN questions compared to other sources for being balanced/unbiased
      (p < 0.001), mentioning areas of uncertainty (p < 0.001), and describing risks of
      PT (p < 0.001). PCWs scored higher for describing the benefits of treatment (p =
      0.003). CONCLUSIONS: Patients should be aware that online information regarding
      PT for prostate cancer may represent marketing by proton centers rather than
      comprehensive and unbiased patient education. An awareness of these results will
      also better prepare clinicians to address the potential biases of patients with
      prostate cancer who search the Internet for health information.

PMID- 24331343
TI  - Epidural anesthesia can block the negative effects of prostaglandin mediators
      during prostate surgery.
AB  - INTRODUCTION: Inflammation plays a key role in the development of benign
      prostatic hyperplasia. Prostaglandin E2 (PGE2) is an important inflammation
      factor found in enlarged prostatic tissue that can be the main cause of
      inflammatory pain. The aim of this study was to investigate whether epidural
      anesthesia can block the negative effects of prostaglandin mediators during
      prostate surgery. MATERIALS AND METHODS: The study included 60 patients who
      underwent open prostatectomy. All patients were randomly allocated to one of two
      study groups. The first group received general anesthesia and the second group a
      combination of general and epidural anesthesia. Main outcome measures were plasma
      concentration of PGE2, adrenaline, noradrenaline, and dopamine, before induction
      of anesthesia and at the time of enucleation. RESULTS: Preoperative serum
      concentrations of PGE2 were high in both groups. During enucleation, serum
      concentrations of adrenaline, noradrenaline, and dopamine increased, followed by
      a rise of systolic and diastolic blood pressure in the group of patients that
      received only general anesthesia. Serum concentration of PGE2 was at the same
      level as before induction of anesthesia in both groups. CONCLUSION: Epidural
      anesthesia blocks transmission of painful stimulus through the spinal cord caused
      by prostaglandin release and prevents the rise of catecholamines and blood
      pressure. Open prostatectomy can become a safer procedure performed under a
      combination of general and epidural anesthesia. Negative intraoperative effects
      of inflammatory prostate mediators during other techniques for prostate surgery
      could also be blocked with epidural anesthesia.

PMID- 24331344
TI  - Deferred permanent prostate seed brachytherapy does not affect PSA outcome:
      results from a large retrospective cohort.
AB  - INTRODUCTION: To examine the outcome of deferred permanent seed brachytherapy
      (BT) for localized low or intermediate risk prostate cancer in order to identify
      predictors of delayed therapy (DT). MATERIALS AND METHODS: We studied 714
      patients treated with BT with or without external radiotherapy. DT was defined as
      no treatment for > 350 days after the first biopsy with cancer. Factors
      influencing DT were analyzed. PSA outcome was assessed only in patients with a
      follow up >= 24 months. Patients with DT were compared to patients treated < 350
      days using non-parametric tests. Multivariate analysis was performed using linear
      regression analysis. RESULTS: BT was deferred in 125 patients (17.5%) for a
      median of 607 days (IQR 445-926). Patients with DT were older (71 years versus 69
      years, p = 0.04) and had significantly less aggressive disease (percentage of
      positive biopsies, T1 disease, Gleason 6) on univariate analysis. On multivariate
      analysis, age (p = 0.01) and Gleason score (p = 0.05) were predictive for DT.
      Median (range) PSA follow up for DT patients was 36 months (24-78). The rate of
      patients with DT attaining a PSA at last follow up of < 0.2 ng/mL, < 0.5 ng/mL
      and <= 1 ng/mL was 53%, 73 % and 95%, respectively; only one patient (1.6 %) had
      biochemical failure (p = 0.61 compared to immediate BT). Multivariate analysis
      showed that age was predictive (p = 0.02) for a nadir of < 0.5 ng/mL and < 0.2
      ng/mL (p = 0.017) and T-stage for a PSA < 0.2 ng/mL (p = 0.04). CONCLUSIONS: This
      is the largest analysis of the effects of deferred BT showing a promising rate of
      early PSA response.

PMID- 24331346
TI  - Audience response system: a new learning tool for urologic conferences.
AB  - INTRODUCTION: Audience response systems (ARS) have not been used to gauge
      knowledge transfer and retention in the setting of large medical conferences. In
      this study, we explore the utility of an ARS as an educational tool in the
      setting of a large urology conference. MATERIALS AND METHODS: At the 2011 joint
      meeting of the Mid-Atlantic and New England sections of the American Urological
      Association, conference attendees were able to use a web-based and cell-phone
      accessed ARS. At the meeting, six ARS questions were asked during five point
      counterpoint debate topics covering areas of prostate cancer, incontinence,
      pediatrics, stone disease, and renal cancer. Questions were presented by expert
      representatives from each of the sections; questions were structured as
      management options for predefined cases. At the beginning and end of each 15
      minute session, attendees were asked to use the ARS to select the best management
      option. RESULTS: In five out of the six questions (83%) more than 10% of
      responses were changed following the presentation of the point-counterpoint
      session and a > 25% change in response was noted in two out of the six questions
      (33%). A statistically significant change was noted for one question relating to
      management of urolithiasis in pregnancy (p = 0.037). CONCLUSIONS: This is the
      first study which demonstrates the potential utility of an ARS in a large urology
      conference. With further research it may be possible to use this technology to
      identify high-yield topics for medical education and improve outcomes during
      lecture-based educational activities.

PMID- 24331345
TI  - Estimating the risk of chronic kidney disease after nephrectomy.
AB  - INTRODUCTION: To identify factors associated with the development of chronic
      kidney disease (CKD) after nephrectomy and to create a clinical model to predict
      CKD after nephrectomy for kidney cancer for clinical use. MATERIALS AND METHODS:
      We identified 144 patients who had normal renal function (eGFR > 60) prior to
      undergoing nephrectomy for kidney cancer. Selected cases occurred between 2007
      and 2010 and had at least 30 days follow up. Sixty-six percent (n = 95) underwent
      radical nephrectomy and 62.5% (n = 90) developed CKD (stage 3 or higher)
      postoperatively. We used univariable analysis to screen for predictors of CKD and
      multivariable logistic regression to identify independent predictors of CKD and
      their corresponding odds ratios. Interaction terms were introduced to test for
      effect modification. To protect against over-fitting, we used 10-fold cross
      validation technique to evaluate model performance in multiple training and
      testing datasets. Validation against an independent external cohort was also
      performed. RESULTS: Of the variables associated with CKD in univariable analysis,
      the only independent predictors in multivariable logistic regression were patient
      age (OR = 1.27 per 5 years, 95% CI: 1.07-1.51), preoperative glomerular
      filtration rate (GFR), (OR = 0.70 per 10 mL/min, 95% CI: 0.56-0.89), and receipt
      of radical nephrectomy (OR = 4.78, 95% CI: 2.08-10.99). There were no significant
      interaction terms. The resulting model had an area under the curve (AUC) of
      0.798. A 10-fold cross-validation slightly attenuated the AUC to 0.774 and
      external validation yielded an AUC of 0.930, confirming excellent model
      discrimination. CONCLUSIONS: Patient age, preoperative GFR, and receipt of a
      radical nephrectomy independently predicted the development of CKD in patients
      undergoing nephrectomy for kidney cancer in a validated predictive model.

PMID- 24331347
TI  - Patterns of urinary catheter consults in a tertiary care hospital.
AB  - INTRODUCTION: We reviewed the consultation patterns for difficult urethral
      catheter placement in tertiary care hospitals and developed a treatment algorithm
      for this common request. MATERIALS AND METHODS: We identified all urethral
      catheter consults obtained by urology residents at three tertiary care hospitals
      from October 2009 through October 2010. Only consults for inability to place
      urethral catheter by the referring team were included; hematuria or clot
      retention were excluded. Patient age, date of consultation, consulting service,
      prior urologic history, initial number of attempts, and final outcome were
      recorded. RESULTS: Eighty-one consults were recorded. Seventy-seven (96%) were
      male; the median age was 65 years. The most common consulting services were
      internal medicine (35%), intraoperative consults (17%), and the intensive care
      unit (17%). In 90% of cases, an initial attempt at catheter placement was
      attempted; 62% of these were made by nurses. Over half of patients had known
      urologic pathology. In 70% of cases, successful placement without other adjuncts
      was achieved by the urology resident. Twenty percent of patients required
      cystoscopic manipulation; nine percent required suprapubic tube placement.
      CONCLUSIONS: Catheterization was achieved without adjunct procedures in the
      majority of consults. These results support an algorithm in which all patients
      without a prior history of lower urinary tract pathology should undergo an
      initial placement attempt by the primary service physician. They also underscore
      the need for educational efforts to improve non-urologists' comfort level with
      placement of a standard Foley or Coude catheter.

PMID- 24331348
TI  - Predictive analysis of factors associated with percutaneous stone surgery
      outcomes.
AB  - INTRODUCTION: The aim of this study is to identify surgical, patient- and stone
      related factors predictive of clinical success and complications after
      percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: We prospectively
      studied 100 consecutive PCNL procedures. Univariate and multiple regression
      models were used in order to identify which variables could act as independent
      predictors of PCNL outcomes. Success was defined as complete absence of fragments
      in a non-contrast CT. The Clavien-modified grading system was used to classify
      the complications. RESULTS: Univariate analysis showed that patients rendered
      stone-free had a significantly lower stone burden, shorter operating times,
      single stones and non-struvite composed calculi. Patient age, nephrostomy tract
      dilation with high pressure balloon and a stone composition different to struvite
      behaved as significant protective factors for complications. Logistic regression
      models revealed that the main independent prognostic factor for success was stone
      surface (OR = 0.997 per mm2, p = 0.000), followed by multiple stones (OR = 0.203,
      p = 0.050). On the other hand, struvite composition (OR = 5.911, p = 0.028) was
      an independent predictor for the development of complications, whilst age (OR =
      0.936, p = 0.012) and high pressure balloon dilation (OR = 0.041, p = 0.007) were
      rendered independent protective variables. CONCLUSIONS: Stone burden and multiple
      calculi in the kidney affect the immediate stone-free rate, whilst Amplatz
      dilation, struvite stones and young patients lead to a higher incidence of
      postoperative complications. This information can be very useful for patient
      counseling, regarding percutaneous kidney stone management.

PMID- 24331349
TI  - The not-so-simple renal cyst.
AB  - Simple renal cysts are most commonly found in the elderly, male population. The
      majority of simple renal cysts remain untreated, except on the rare occasion when
      they become complicated with hemorrhage, infection or rupture. We present the
      case of a 31-year-old female with a simple renal cyst which was initially treated
      as acute pyelonephritis. A high clinical suspicion led to the diagnosis of an
      infected renal cyst which was treated with antibiotic therapy and radiological
      drainage. There were minimal complications and the patient made an uneventful
      recovery. 

PMID- 24331350
TI  - The use of adhesion barrier film as an alternative to omental wrap in open
      ureterolysis.
AB  - Retroperitoneal fibrosis (RPF) is a rarely occurring disease process
      characterized by the development of fibrous plaques that encase retroperitoneal
      organs and major vessels. The most common sequelae is obstructive uropathy
      secondary to ureteral compression. Ureterolysis with intraperitoneal
      transposition and omental wrapping has historically been a popularized means to
      relieve ureteral obstruction. We present the case of a 47-year-old man with
      bilateral hydronephrosis secondary to RPF. Due to insufficient length of omentum,
      we report the first documented use of SurgiWrap to wrap the ureters to minimize
      the future possibility of recurrent/continued fibrosis, compression, and ureteral
      obstruction. 

PMID- 24331351
TI  - Robotic assisted laparoscopic excision of a pelvic angiomyofibroblastoma-like
      tumor.
AB  - Angiomyofibroblastoma (AMF) is a rare benign tumor of the female genital tract.
      Three cases of AMF-like tumors of the male genital tract have been reported in
      the literature. We present the first documented case of an AMF-like soft tissue
      tumor of the male pelvis excised with robotic assisted laparoscopic surgery. 

PMID- 24331352
TI  - Metastatic retroperitoneal hemangiopericytoma.
AB  - Hemangiopericytomas are rare mesenchymal lesions arising from pericytes within
      the walls of capillaries. They often have an unpredictable course. We present a
      case of a large retroperitoneal hemangiopericytoma in a 65-year-old woman who
      initially presented with upper gastrointestinal discomfort. Following
      exptirpative surgery, pathology was consistent with hemangiopericytoma of low
      malignant potential. Widespread metastasis was discovered on follow up imaging,
      17 months following surgery. To our knowledge, this is the first case report
      demonstrating a primary retroperitoneal hemangioperictoma with confirmed
      metastases. 

PMID- 24331353
TI  - Robot assisted radical prostatectomy: how I do it. Part II: Surgical technique.
AB  - The introduction of the "da Vinci Robotic Surgical System" (Intuitive Surgical,
      Sunnyvale, CA, USA) has been an important step towards a minimally invasive
      approach to radical prostatectomy. Technologic peculiarities, such as three
      dimensional vision, wristed instrumentation with seven degrees of freedom of
      motion, lack of tremor, a 10x-magnification and a comfortable seated position for
      the surgeon has added value to the procedure for the surgeon and the patient. In
      this article, we describe the 9 step surgical technique for robot assisted
      radical prostatectomy (RARP) that is currently used in our institution
      (University of Montreal Hospital Center (CHUM) - Hopital St-Luc). We use the four
      arm da Vinci Surgical System. Our experience with RARP is now over 250 cases with
      the senior surgeon having performed over 1200 RARPs and we have continually
      refined our technique to improve patient outcomes. 

PMID- 24331354
TI  - Outcomes with delayed dorsal vein complex ligation during robotic assisted
      laparoscopic prostatectomy.
AB  - INTRODUCTION: There are many concerns expressed by urologists performed robotic
      assisted laparoscopic prostatectomy (RALP) regarding management of the dorsal
      vein complex (DVC). We sought to examine the influence of delayed DVC ligation
      versus standard DVC ligation on the apical surgical margin status and other key
      surgical parameters following RALP. MATERIALS AND METHODS: The Columbia
      University Urologic Oncology Database was retrospectively reviewed to identify
      patients who underwent RALP between 2008-2011. Operative records were analyzed to
      determine whether the DVC was ligated in the 'standard' or 'delayed' manner. The
      standard group had the DVC ligated prior to the apical dissection; in the delayed
      group, the DVC was initially transected and subsequently oversewn after
      completion of the apical dissection. Clinical and pathologic data was
      retrospectively evaluated and stratified by the type of DVC ligation to compare
      positive apical margin rates based on DVC-control technique. RESULTS: A total of
      244 patients were identified, including 118 in the standard group and 126 in the
      delayed group. Estimated blood loss (112 mL versus 122 mL), operative time (132
      min versus 126 min), and postoperative continence rates (81% versus 84% at 3
      months) were similar between the standard and delayed DVC groups (p = NS). Apical
      margin status was also similar in the two groups, with 3.4% having a positive
      surgical margin in the standard DVC ligation arm, and 1.6% having a positive
      margin in the delayed DVC ligation arm (p = 0.43). CONCLUSIONS: Delayed DVC
      ligation after apical dissection is a safe approach with comparable surgical
      outcomes during RALP. From a technical standpoint, we feel it allows for improved
      visualization of the apical dissection and therefore has become standard practice
      at our institution.

PMID- 24331355
TI  - Effectiveness of a dedicated robot-assisted surgery training program.
AB  - INTRODUCTION: Robot-assisted surgery (RAS) has been integrated into the surgical
      armamentarium and generated wide-spread interest among practicing, non-robotic
      surgeons (NRS). While methods for training novice non-robotic surgeons have
      emerged, the effectiveness of these training programs has endured minimal
      scrutiny. This study aims to establish effectiveness of the RAST training
      program. MATERIALS AND METHODS: A formal RAST program was established at Roswell
      Park Cancer Institute (RPCI) in 2008. From July 2010 to October 2012, 43 non
      robotic surgeons participated in the program. The 1 to 4 week program included
      the validated fundamentals skills of robotic surgery (FSRS) curriculum, hands-on
      bedside trouble-shooting training, case observation with an expert robotic
      surgeon, hands on surgical training (HoST) procedure modules, da Vinci robotic
      surgical hands-on experience and finally a compulsory animal laboratory utilizing
      the da Vinci. As part of our training and credentialing quality assurance
      program, all participants were prospectively evaluated employing a survey. This
      survey aimed to evaluate the enduring impact of the RAST through time-sensitive
      interventions that allowed participants to reacclimatize themselves to their
      prospective practice as independently performing surgeons. RESULTS: The survey
      responses received from the participating NRS were collected over 27 months, with
      a response rate of 84%. The average follow up period post-RAST completion was 6
      months (2-19). Overall, participants felt that the FSRS curriculum (81%), bedside
      trouble shooting (7%), and animal laboratory (53%) were beneficial program
      features that enabled NRS to become adequately acquainted with the basic
      principles of RAS. Approximately 5 weeks after RAST program completion, 64% of
      surgeons performed robot-assisted surgery. The two most commonly performed
      procedures were robot-assisted radical prostatectomy and gastrointestinal
      surgeries where eight surgeons performed independently while 12 performed
      procedures under the supervision of an expert robotic surgeon. The overall
      conversion rate to open was reported to be 1.3%. CONCLUSIONS: A dedicated
      surgical training program focused on learning key steps of RAS enabled most
      participants to successfully incorporate and maintain their RAS skills in
      clinical practice.

PMID- 24331356
TI  - Methylation at a transcription factor-binding site on the 5-HT1A receptor gene
      correlates with negative symptom treatment response in first episode
      schizophrenia.
AB  - Individual variability and inadequate response of negative symptoms are major
      limitations of antipsychotic treatment in schizophrenia. A functional
      polymorphism, rs6295, in the 5-HT1A-receptor gene (HTR1A) contributes to this
      variability in negative symptom response. The DNA sequence containing rs6295 is
      rich in cytosine methylation (CpG) sites; CpG methylation is an epigenetic factor
      that, like rs6295, can modify transcriptional control. To investigate whether DNA
      methylation influences response to antipsychotic treatment, we determined
      methylation at CpG sites close to rs6295 in DNA from 82 Chinese subjects with a
      first psychotic episode. Methylation of one CpG site within a recognition
      sequence for HES transcriptional repressors was found to correlate with changes
      in total PANSS score (p = 0.006) and negative factor sub-score (p < 0.001)
      following 10 wk initial antipsychotic treatment, as well as with baseline
      negative factor score (p = 0.019); the effect on symptom change remained after
      correction for this baseline score. An effect of rs6295 on negative symptom
      response was not seen in this sample, which may not have provided sufficient
      power for the pharmacogenetic association. These preliminary results indicate
      that epigenetic modification of transcriptional regulation by specific cytosine
      methylation may modulate HTR1A expression, resulting in effects on emotional
      dysfunction and negative symptom response to antipsychotic treatment.

PMID- 24331357
TI  - Mitochondrial dysfunction in neurological diseases. Introduction.

PMID- 24331358
TI  - Mitochondrial dysfunction in autism.
AB  - Using data of the current prevalence of autism as 200:10,000 and a 1:2000
      incidence of definite mitochondrial (mt) disease, if there was no linkage of
      autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110
      subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would
      have mt disease. The co-occurrence of autism and mt disease is much higher than
      these figures, suggesting a possible pathogenetic relationship. Such hypothesis
      was initially suggested by the presence of biochemical markers of abnormal mt
      metabolic function in patients with ASD, including elevation of lactate,
      pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine
      level in plasma; and level of organic acids in urine, and by demonstrating
      impaired mt fatty acid beta-oxidation. More recently, mtDNA genetic mutations or
      deletions or mutations of nuclear genes regulating mt function have been
      associated with ASD in patients or in neuropathologic studies on the brains of
      patients with autism. In addition, the presence of dysfunction of the complexes
      of the mt respiratory chain or electron transport chain, indicating abnormal
      oxidative phosphorylation, has been reported in patients with ASD and in the
      autopsy samples of brains. Possible pathogenetic mechanisms linking mt
      dysfunction and ASD include mt activation of the immune system, abnormal mt
      Ca(2+) handling, and mt-induced oxidative stress. Genetic and epigenetic
      regulation of brain development may also be disrupted by mt dysfunction,
      including mt-induced oxidative stress. The role of the purinergic system linking
      mt dysfunction and ASD is currently under investigation. In summary, there is
      genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis
      of ASD in a subset of children. To determine the prevalence and type of genetic
      and biochemical mt defects in ASD, there is a need for further research using the
      latest genetic technology such as next-generation sequencing, microarrays,
      bioinformatics, and biochemical assays. Because of the availability of potential
      therapeutic options for mt disease, successful research results could translate
      into better treatment and outcome for patients with mt-associated ASD. This
      requires a high index of suspicion of mt disease in children with autism who are
      diagnosed early. 

PMID- 24331360
TI  - Mitochondrial dysfunction in migraine.
AB  - Migraine is the most frequent type of headache in children. In the 1980s,
      scientists first hypothesized a connection between migraine and mitochondrial
      (mt) disorders. More recent studies have suggested that at least some subtypes of
      migraine may be related to a mt defect. Different types of evidence support a
      relationship between mitochondria (mt) and migraine: (1) Biochemical evidence:
      Abnormal mt function translates into high intracellular penetration of Ca(2+),
      excessive production of free radicals, and deficient oxidative phosphorylation,
      which ultimately causes energy failure in neurons and astrocytes, thus triggering
      migraine mechanisms, including spreading depression. The mt markers of these
      events are low activity of superoxide dismutase, activation of cytochrome-c
      oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of
      phosphocreatine-inorganic phosphate and N-acetylaspartate-choline. (2)
      Morphologic evidence: mt abnormalities have been shown in migraine sufferers, the
      most characteristic ones being direct observation in muscle biopsy of ragged red
      and cytochrome-c oxidase-negative fibers, accumulation of subsarcolemmal mt, and
      demonstration of giant mt with paracrystalline inclusions. (3) Genetic evidence:
      Recent studies have identified specific mutations responsible for migraine
      susceptibility. However, the investigation of the mtDNA mutations found in
      classic mt disorders (mt encephalomyopathy with lactic acidosis and stroke-like
      episodes, myoclonus epilepsy with ragged red fibers, Kearns-Sayre syndrome, and
      Leber hereditary optic neuropathy) has not demonstrated any association.
      Recently, 2 common mtDNA polymorphisms (16519C->T and 3010G->A) have been
      associated with pediatric cyclic vomiting syndrome and migraine. Also, POLG
      mutations (eg, p.T851 A, p.N468D, p.Y831C, p.G517V, and p.P163S) can cause
      disease through impaired replication of mtDNA, including migraine. Further
      studies to investigate the relationship between mtDNA and migraine will require
      very large sample sizes to obtain statistically significant results. (4)
      Therapeutic evidence: Several agents that have a positive effect on mt metabolism
      have shown to be effective in the treatment of migraines. The agents include
      riboflavin (B2), coenzyme Q10, magnesium, niacin, carnitine, topiramate, and
      lipoic acid. Further study is warranted to learn how mt interact with other
      factors to cause migraines. This will facilitate the development of new and more
      specific treatments that will reduce the frequency or severity or both of this
      disease.

PMID- 24331359
TI  - Mitochondrial dysfunction in epilepsy.
AB  - Epilepsy is the most common neurologic disorder worldwide and is characterized by
      recurrent unprovoked seizures. The mitochondrial (mt) respiratory chain is the
      final common pathway for cellular energy production through the process of
      oxidative phosphorylation. As neurons are terminally differentiated cells that
      lack significant regenerative capacity and have a high energy demand, they are
      more vulnerable to mt dysfunction. Therefore, epileptic seizures have been well
      described in several diseases such as mt encephalomyopathy, lactic acidosis, and
      stroke-like episodes and myoclonic epilepsy and ragged red fibers, which are
      caused by gene mutations in mtDNA, among others. Mutations in nuclear DNA
      regulating mt function are also being described (eg, POLG gene mutation). The
      role of mitochondria (mt) in acquired epilepsies, which account for about 60% of
      all epilepsies, is equally important but less well understood. Oxidative stress
      is one of the possible mechanisms in the pathogenesis of epilepsy resulting from
      mt dysfunction gradually disrupting the intracellular Ca(2+) homeostasis, which
      modulates neuronal excitability and synaptic transmission, making neurons more
      vulnerable to additional stress, and leading to energy failure and neuronal loss
      in epilepsy. Antiepileptic drugs (AEDs) also affect mt function in several ways.
      There must be caution when treating epilepsy in patients with known mt disorders
      as some AEDs are toxic to the mt. This review summarizes our current knowledge of
      the effect of mt disorders on epilepsy, of epileptic seizures on mt, and of AEDs
      on mt function and the implications of all these interactions for the management
      of epilepsy in patients with or without mt disease. 

PMID- 24331361
TI  - Mitochondrial dysfunction in demyelinating diseases.
AB  - Dysfunction of the mitochondrial (mt) system is thought to play an important role
      in the mechanism of progression of various neurodegenerative disorders, including
      demyelinating disorders. They are characterized by neuroinflammation, ultimately
      leading to neurodegeneration. Mitochondria (mt) dysfunction is closely related to
      the mechanism of neuroinflammation, causing increased production of reactive
      oxygen species, which is detrimental to neurons and glia. Vice versa,
      neuroinflammation is increasingly recognized to produce mt failure, which then
      contributes to further neuronal injury and degeneration. Multiple sclerosis and X
      linked adrenoleukodystrophy are examples of neurodemyelinating diseases that
      despite having a diverse etiology have in common a progressive course and
      significant neuroinflammation and neurodegeneration, leading to severe neurologic
      disability. The scientific community has become increasingly interested in how mt
      dysfunction relates to neuroinflammation and demyelination and what role it may
      play in the natural history of progressive demyelinating diseases. Research
      studies investigating how mt failure contributes to the progression of these
      conditions are emerging. A better understanding of the role of oxidative stress
      in progressive inflammatory demyelinating diseases might generate new potential
      neuroprotective therapeutic approaches for these devastating neurologic
      conditions. 

PMID- 24331362
TI  - Mitochondrial dysfunction in neuromuscular disorders.
AB  - This review deciphers aspects of mitochondrial (mt) dysfunction among
      nosologically, pathologically, and genetically diverse diseases of the skeletal
      muscle, lower motor neuron, and peripheral nerve, which fall outside the
      traditional realm of mt cytopathies. Special emphasis is given to well
      characterized mt abnormalities in collagen VI myopathies (Ullrich congenital
      muscular dystrophy and Bethlem myopathy), megaconial congenital muscular
      dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear
      myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy,
      Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies.
      Among inflammatory myopathies, mt abnormalities are more prominent in inclusion
      body myositis and a subset of polymyositis with mt pathology, both of which are
      refractory to corticosteroid treatment. Awareness is raised about instances of
      phenotypic mimicry between cases harboring primary mtDNA depletion, in the
      context of mtDNA depletion syndrome, and established neuromuscular disorders such
      as spinal muscular atrophy. A substantial body of experimental work, derived from
      animal models, attests to a major role of mitochondria (mt) in the early process
      of muscle degeneration. Common mechanisms of mt-related cell injury include
      dysregulation of the mt permeability transition pore opening and defective
      autophagy. The therapeutic use of mt permeability transition pore modifiers holds
      promise in various neuromuscular disorders, including muscular dystrophies. 

PMID- 24331363
TI  - Mitochondrial dysfunction in gliomas.
AB  - Mitochondrial (mt) dysfunction in gliomas has been linked to abnormalities of mt
      energy metabolism, marked by a metabolic shift from oxidative phosphorylation to
      glycolysis ("Warburg effect"), disturbances in mt membrane potential regulation
      and apoptotic signaling, as well as to somatic mutations involving the Krebs
      cycle enzyme isocitrate dehydrogenase. Evolving biological concepts with
      potential therapeutic implications include interaction between microtubule
      proteins and mitochondria (mt) in the control of closure of voltage-dependent
      anion channels and in the regulation of mt dynamics and the mt-endoplasmic
      reticulum network. The cytoskeletal protein betaIII-tubulin, which is
      overexpressed in malignant gliomas, has emerged as a prosurvival factor
      associated in part with mt and also as a marker of chemoresistance. Mt-targeted
      therapeutic strategies that are discussed include the following: (1) metabolic
      modulation with emphasis on dichloroacetate, a pyruvate dehydrogenase kinase
      inhibitor; (2) tumor cell death via apoptosis induced by tricyclic
      antidepressants, microtubule-modulating drugs, and small molecules or compounds
      capable of inflicting reactive oxygen species-dependent tumor cell death; and (3)
      pretreatment mt priming and mt-targeted prodrug cancer therapy. 

PMID- 24331364
TI  - Assessing and comparing the performance of molecular diagnostic tests.

PMID- 24331365
TI  - Revisiting oversight and regulation of molecular-based laboratory-developed
      tests: a position statement of the Association for Molecular Pathology.
AB  - Since 2006, the US Food and Drug Administration, Congress, and other policymakers
      have explored the appropriate way to guarantee the clinical and analytical
      validity of laboratory-developed tests. In the past, the Association for
      Molecular Pathology has publicly urged the Food and Drug Administration to
      exercise caution in implementing regulatory changes that could potentially hinder
      innovation or interfere with the practice of medicine. In 2012, the Association
      for Molecular Pathology Professional Relations Committee chose to develop this
      paper with the goal of outlining the best methods for ensuring appropriate
      oversight and validation of molecular diagnostic procedures. At the conclusion of
      this process, the workgroup reaffirmed the Association's previous position that
      the Centers for Medicare and Medicaid Services Clinical Laboratory Improvement
      Amendments program can provide the appropriate level of oversight for the vast
      majority of diagnostic tests. 

PMID- 24331366
TI  - Sensitive and rapid detection of Chlamydia trachomatis by recombinase polymerase
      amplification directly from urine samples.
AB  - Chlamydia trachomatis is the most common sexually transmitted human pathogen.
      Infection results in minimal to no symptoms in approximately two-thirds of women
      and therefore often goes undiagnosed. C. trachomatis infections are a major
      public health concern because of the potential severe long-term consequences,
      including an increased risk of ectopic pregnancy, chronic pelvic pain, and
      infertility. To date, several point-of-care tests have been developed for C.
      trachomatis diagnostics. Although many of them are fast and specific, they lack
      the required sensitivity for large-scale application. We describe a rapid and
      sensitive form of detection directly from urine samples. The assay uses
      recombinase polymerase amplification and has a minimum detection limit of 5 to 12
      pathogens per test. Furthermore, it enables detection within 20 minutes directly
      from urine samples without DNA purification before the amplification reaction.
      Initial analysis of the assay from clinical patient samples had a specificity of
      100% (95% CI, 92%-100%) and a sensitivity of 83% (95% CI, 51%-97%). The whole
      procedure is fairly simple and does not require specific machinery, making it
      potentially applicable in point-of-care settings. 

PMID- 24331367
TI  - Influence of pathogenic bacteria species present in the postpartum bovine uterus
      on proteome profiles.
AB  - In the first 2-3 weeks after parturition >90% of dairy cows will have some form
      of uterine infection. Uterine contamination with pathogens, such as Trueperella
      (formerly Arcanobacterium) pyogenes increases the risk of developing more severe
      endometritis, which can reduce conception rates. In this study, we compared the
      uterine proteome of cows infected with Trueperella pyogenes with that of
      uninfected cows, using 2D gel electrophoresis, and identified annexins A1 and A2
      (ANXA1 and ANXA2), apolipoprotein A-1, calprotectin (S100A9), cathelicidin,
      enolase 1 (ENO1), peptidoglycan recognition protein 1 (PGLYRP1), phosphoglycerate
      mutase 1 (PGAM1), serine dehydratase (SDS) and serine protease inhibitors
      (SERPIN) B1, B3 and B4 proteins as differing in abundance in endometritis.
      Subsequently, levels of ten of these proteins were monitored in uterine samples
      collected from a herd of lactating, dairy cows at 15 and 42 days post-partum
      (DPP). The levels were compared with the cytology scores of the samples and the
      bacterial species isolated from the uterus. Cathelicidin, PGLYRP1, SERPINB1 and
      S100A9 levels at 15DPP showed strong positive correlations (r=0.78, 0.80, 0.79,
      and 0.68 respectively; P<0.001) with % of polymorphonuclear neutrophils (PMN).
      When compared with other bacterial pathogens identified, Streptococcus agalactiae
      and Truperella pyogenes induced increased expression of the indicator proteins,
      suggesting that these organisms may adversely affect the subsequent ability of
      the cow to conceive. Interestingly, there was no difference in the proportion of
      cows pregnant at 6 and 17 weeks after start of mating between the cows with high
      or low %PMN. 

PMID- 24331368
TI  - Path analysis of suicide ideation in older people.
AB  - BACKGROUND: Suicide among older people is one of the most rapidly emerging
      healthcare issues. The objective of this study was to identify the factors
      associated with suicide ideation in the aged population in South Korea. METHODS:
      The study recruited 684 subjects older than 65 years old (males = 147, females =
      537, mean age = 78.20+/-7.02 years), and trained interviewers performed the
      interviews. The study was performed as part of a community mental health suicide
      prevention program. The subjects' socio-demographic data, physical health,
      alcohol problems, social relationships, psychological well-being, and depression
      severity were all considered. The Korean version of the Beck Scale for Suicide
      Ideation (K-BSI) was used to evaluate the intensity of suicide ideation.
      Correlation and hierarchical multiple regression analyses were performed to
      identify the factors associated with the K-BSI. The study results were tested
      using a path analysis. RESULTS: Depression severity was positively correlated
      with suicide ideation, and economic status, psychological well-being, and social
      relationships were negatively correlated with suicide ideation. Depression
      severity had the largest direct impact, and economic status and social
      relationships had indirect impacts on suicide ideation. Psychological well-being
      exerted both direct and indirect influences. CONCLUSION: Depression severity was
      the most important predictor of suicide ideation among older people. Other direct
      and indirect factors played secondary roles. Effective suicide prevention
      strategies should focus on early detection and active intervention for
      depression. Socio-economic programs may also indirectly reduce suicide ideation
      among the aged population.

PMID- 24331369
TI  - Aspirin reduces lung cancer metastasis to regional lymph nodes.
AB  - BACKGROUND: Lung cancer is the main cause of cancer-related death worldwide. The
      high mortality is probably attributable to early metastasis; however, the
      mechanism underlying metastasis to regional lymph nodes is still unknown.
      Cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) induces tumor growth and
      metastasis and is associated with a poor prognosis. The present study
      investigated the effect of an authentic COX inhibitor, aspirin, on regional lymph
      node metastasis during the development of lung cancer in mice. METHODS: An
      orthotopic intrapulmonary implantation model based on male C57BL/6 (6-8-weeks
      old) mice was used. The lungs were injected with a solution containing Lewis lung
      carcinoma (LLC) cells overexpressing green fluorescent protein (GFP) and BD
      Matrigel((r)). The effect of aspirin on mediastinal lymph node metastasis of LCC
      cells from the primary injection sites was then examined. RESULTS: The
      implantation process took approximately 30 s per mouse and operative mortality
      was 10%. Single pulmonary nodules developed at the implanted site in 95% of
      animals, and regional mediastinal lymph node metastasis was observed at 14 days
      post-LLC-GFP cell injection in all mice that formed a primary lung tumor. The
      mean survival time of mice injected with LLC-GFP cells was 15+/-3 days (range, 12
      22 days). Histopathological analysis revealed that no metastatic tumors developed
      in the regional mediastinal lymph nodes by Day 10-12 post-LLC-GFP cell injection
      and no metastasis to distant organs or distant lymph nodes was observed by Day 21
      post-injection. Oral administration of aspirin (100 mg/kg, twice a day) after LLC
      GFP cell injection inhibited metastasis to the regional lymph nodes, with no
      significant suppression of primary tumor growth in the lungs. Aspirin treatment
      led to a significant reduction in mortality (P<0.0001). CONCLUSIONS: The present
      lymph node metastasis model is useful for evaluating the efficacy of agents that
      inhibit tumor metastasis to the regional lymph nodes. Aspirin reduced the
      metastasis of LLC-GFP cells injection to the regional lymph nodes, with a
      significant reduction in mortality. These findings suggested that COX inhibitors
      have potential for preventing lymph node metastasis.

PMID- 24331370
TI  - Prototyping of poly(dimethylsiloxane) interfaces for flow gating, reagent mixing,
      and tubing connection in capillary electrophoresis.
AB  - Integrated microfluidic systems coupled with electrophoretic separations have
      broad application in biologic and chemical analysis. Interfaces for the
      connection of various functional parts play a major role in the performance of a
      system. Here, we developed a rapid prototyping method to fabricate monolithic
      poly(dimethylsiloxane) (PDMS) interfaces for flow-gated injection, online reagent
      mixing, and tube-to-tube connection in an integrated capillary electrophoresis
      (CE) system. The basic idea was based on the properties of PDMS: elasticity,
      transparency, and suitability for prototyping. The molds for these interfaces
      were prepared by using commercially available stainless steel wires and nylon
      lines or silica capillaries. A steel wire was inserted through the diameter of a
      nylon line and a cross format was obtained as the mold for PDMS casting of flow
      gates and 4-way mixers. These interfaces accommodated tubing connection through
      PDMS elasticity and provided easy visual trouble shooting. The flow gate used
      smaller channel diameters, thus reducing flow rate by 25-fold for effective
      gating compared with mechanically machined counterparts. Both PDMS mixers and the
      tube-to-tube connectors could minimize the sample dead volume by using an
      appropriate capillary configuration. As a whole, the prototyped PDMS interfaces
      are reusable, inexpensive, convenient for connection, and robust when integrated
      with the CE detection system. Therefore, these interfaces could see potential
      applications in CE and CE-coupled systems. 

PMID- 24331371
TI  - Facile preparation of protein stationary phase based on polydopamine/graphene
      oxide platform for chip-based open tubular capillary electrochromatography
      enantioseparation.
AB  - A novel chip-based enantioselective open-tubular capillary electrochromatography
      (OT-CEC) was developed employing bovine serum albumin (BSA) conjugated
      polydopamine-graphene oxide (PDA/GO) nanocomposites (PDA/GO/BSA) as stationary
      phase. After the poly(dimethylsiloxane) (PDMS) microfluidic chip was filled with
      a freshly prepared solution containing dopamine and graphene oxide, PDA/GO
      nanocomposites were formed and deposited on the inner wall of microchannel as
      permanent coating via the oxidation of dopamine by the oxygen dissolved in the
      solution. The PDA/GO-coated PDMS microchips not only have the adhesion of PDA
      that make them easily immobilized in the microchannel, but also have the larger
      surface and excellent biocompatibility of graphene which can incorporate much
      more biomolecules and well maintain their biological activity. In addition,
      incorporation of GO in PDA film can make surface morphology more rough, which is
      beneficial for enhancing the loading capacity of proteins in the microchannels
      and increasing sample capacity of OT-CEC columns. BSA was stably immobilized in
      the PDMS microchannel to fabricate a protein-stationary phase. Compared with the
      native PDMS microchannels, the modified surfaces exhibited much better
      wettability, more stable electroosmotic mobility, and less nonspecific
      adsorption. The efficient separation of chiral amino acids (tryptophan and
      threonine) and chiral dipeptide demonstrate that the constructed OT-CEC columns
      own ideal enantioselectivity. The presented strategy using PDA/GO coating as a
      versatile platform for facile conjugation of proteins may offer new processing
      strategies to prepare a functional surface designed on microfluidic chips. 

PMID- 24331372
TI  - Preparation and characterization of lysine-immobilized poly(glycidyl
      methacrylate) nanoparticle-coated capillary for the separation of amino acids by
      open tubular capillary electrochromatography.
AB  - In this study, poly(glycidyl methacrylate) (PGMA) nanoparticles (NPs) were
      prepared and chemically immobilized for the first time onto a capillary inner
      wall for open tubular capillary electrochromatography (OTCEC). The immobilization
      of PGMA NPs onto the capillary was attained by a ring-opening reaction between
      the NPs and an amino-silylated fused capillary inner surface. Scanning electron
      micrographs clearly demonstrated that the NPs were bound to the capillary inner
      surface in a dense monolayer. The PGMA NP-coated column was then functionalized
      by lysine (Lys). After fuctionalization, the capillary can afford strong anodic
      electroosmotic flow, especially in acidic running buffers. Separations of three
      amino acids (including tryptophan, tyrosine and phenylalanine) were performed in
      NP-modified, monolayer Lys-functionalized and bare uncoated capillaries. Results
      indicated that the NP-coated column can provide more retention and higher
      resolution for analytes due to the hydrophobic interaction between analytes and
      the NP-coating. Run-to-run and column-to-column reproducibilities in the
      separation of the amino acids using the NP-modified column were also
      demonstrated. 

PMID- 24331374
TI  - Patterned deposition at moving contact lines.
AB  - When a simple or complex liquid recedes from a smooth solid substrate it often
      leaves a homogeneous or structured deposit behind. In the case of a receding non
      volatile pure liquid the deposit might be a liquid film or an arrangement of
      droplets depending on the receding speed of the meniscus and the wetting
      properties of the system. For complex liquids with volatile components as, e.g.,
      polymer solutions and particle or surfactant suspensions, the deposit might be a
      homogeneous or structured layer of solute--with structures ranging from line
      patterns that can be orthogonal or parallel to the receding contact line via
      hexagonal or square arrangements of drops to complicated hierarchical structures.
      We review a number of recent experiments and modelling approaches with a
      particular focus on mesoscopic hydrodynamic long-wave models. The conclusion
      highlights open question and speculates about future developments.

PMID- 24331373
TI  - MYOD mediates skeletal myogenic differentiation of human amniotic fluid stem
      cells and regeneration of muscle injury.
AB  - INTRODUCTION: Human amniotic fluid stem (hAFS) cells have been shown to
      differentiate into multiple lineages, including myoblasts. However, molecular
      mechanisms underlying the myogenic differentiation of hAFS cells and their
      regenerative potential for muscle injury remain to be elucidated. METHODS: In
      order to induce myogenic differentiation of hAFS cells, lentiviruses for MYOD
      were constructed and transduced into hAFS cells. Formation of myotube-like cells
      was analyzed by immunocytochemistry, and expression of molecular markers for
      myoblasts was analyzed by reverse transcription polymerase chain reaction and
      Western blotting. For in vivo muscle regeneration, MYOD transduced hAFS cells
      were injected into left tibialis anterior (TA) muscles injured with cardiotoxin,
      and muscle regeneration was analyzed using hematoxylin and eosin,
      immunocytochemistry and formation of neuro-muscular junction. RESULTS: MYOD
      expression in hAFS cells successfully induced differentiation into multinucleated
      myotube-like cells. Consistently, significant expression of myogenic marker
      genes, such as MYOG, DES, DMD and MYH, was induced by MYOD. Analysis of pre
      myogenic factors showed that expression of PAX3, MEOX1 and EYA2 was significantly
      increased by MYOD. MYOD was phosphorylated and localized in the nucleus. These
      results suggest that in hAFS cells, MYOD is phosphorylated and localized in the
      nucleus, thus inducing expression of myogenic factors, resulting in myogenic
      differentiation of hAFS cells. To test regenerative potential of MYOD-transduced
      hAFS cells, we transplanted them into injured muscles of immunodeficient
      BALB/cSlc-nu mice. The results showed a substantial increase in the volume of TA
      muscle injected with MYOD-hAFS cells. In addition, TA muscle tissue injected with
      MYOD-hAFS cells has more numbers of neuro-muscular junctions compared to
      controls, indicating functional restoration of muscle injury by MYOD-hAFS cells.
      CONCLUSIONS: Collectively, our data suggest that transduction of hAFS cells with
      MYOD lentiviruses induces skeletal myogenic differentiation in vitro and
      morphological and functional regeneration of injured muscle in vivo.

PMID- 24331375
TI  - Does knowledge about antiretroviral therapy and mother-to-child transmission
      affect the relationships between HIV status and fertility preferences and
      contraceptive use? New evidence from Nigeria and Zambia.
AB  - The increasing availability of antiretroviral therapy (ART) and drug regimens to
      prevent mother-to-child transmission (PMTCT) has probably changed the context of
      childbearing for people living with HIV. Using data from 2009-2010 community
      based surveys in Nigeria and Zambia, this study explores whether women's
      knowledge about ART and PMTCT influences the relationship between HIV status and
      fertility preferences and contraceptive behaviour. The findings show that women
      living with HIV are more likely to want more children in Nigeria and to want to
      limit childbearing in Zambia compared with HIV-negative women. While there is no
      significant difference in contraceptive use by women's HIV status in the two
      countries, women who did not know their HIV status are less likely to use
      contraceptives relative to women who are HIV-negative. Knowledge about ART
      reduces the childbearing desires of HIV-positive women in Nigeria and knowledge
      about PMTCT increases desire for more children among HIV-positive women in
      Zambia, as well as contraceptive use among women who do not know their HIV
      status. The findings indicate that knowledge about HIV prevention and treatment
      services changes how living with HIV affects childbearing desires and, at least
      in Zambia, pregnancy prevention, and highlight the importance of access to
      accurate knowledge about ART and PMTCT services to assist women and men to make
      informed childbearing decisions. Knowledge about ART and PMTCT should be promoted
      not only through HIV treatment and maternal and newborn care facilities but also
      through family planning centres and the mass media.

PMID- 24331376
TI  - Asthma control in the United States, 2008-2010: indicators of poor asthma
      control.
AB  - BACKGROUND: An estimated 23 million Americans have asthma, of whom at least 12
      million experience an asthma exacerbation every year. Clinical practice
      guidelines focus on asthma control, with an emphasis on reducing both impairment
      and risk. OBJECTIVE: We sought to explore broad patterns of asthma prevalence,
      self-reported medication use, and indicators of control in a nationally
      representative sample. METHODS: The 2008, 2009, and 2010 Medical Expenditure
      Panel Surveys were used to examine the national prevalence of self-reported
      asthma, trends in medication use, and demographic characteristics of asthmatic
      patients. History of lifetime asthma and current diagnosis were ascertained based
      on self-report. Asthma management and control were examined by using patient
      reported medication use. RESULTS: Of the 102,544 subjects asked about an asthma
      diagnosis, 9,782 reported lifetime asthma, and 8,837 reported current asthma.
      Five thousand five subjects (4.8% of the population) reported experiencing an
      asthma exacerbation in the previous year. Four thousand five hundred twenty-one
      subjects used a quick-relief inhaler for asthma symptoms, and 14.6% used more
      than 3 canisters of this type of medication in the past 3 months. Of this group,
      60% were using daily long-term control medication but still required significant
      use of quick-relief inhalers, whereas 28% had never used long-term control
      medication. Of those who had a recent exacerbation, 29% were using daily
      preventive medication, whereas 54% had never used long-term control medication.
      CONCLUSIONS: Improvement of asthma control continues to be a US public health
      concern. Results suggest suboptimal asthma control with underuse of long-term
      control medications, overuse of quick-relief inhalers, and a significant number
      of self-reported asthma exacerbations.

PMID- 24331377
TI  - Effect of confounding cofactors on responses to pollens during natural season
      versus pollen challenge chamber exposure.
AB  - BACKGROUND: The severity of allergic rhinoconjunctivitis (AR) symptomatology
      elicited after exposure to pollen in the absence versus the presence of
      confounding cofactors, such as in a pollen challenge chamber (PCC) and the
      natural pollinating season, respectively, might differ. OBJECTIVE: We sought to
      determine the correlation of AR severity in the natural season versus out-of
      season PCC exposures. METHODS: Twenty-four Virginia live oak (VLO)-positive, 14
      VLO-negative, 16 mountain cedar (MC)-positive, 8 MC-negative, and 26 ragweed
      positive participants recorded AR symptoms (total symptom score [TSS]) during the
      VLO, MC, and ragweed pollinating seasons and during 2 consecutive PCC exposures
      of 3 hours each to these pollens separately. RESULTS: The TSSs recorded before
      the natural season were higher than the pre-PCC values. This prepriming was
      greater among VLO(+) than MC(+) participants, and it blunted further increases in
      TSSs during the VLO natural season. Nonatopic participants were nonreactive in
      the PCC. There was wide variation in the level of AR symptomatology after
      exposure to VLO, MC, or ragweed pollen in the PCC. Prepriming formed the basis
      for higher AR responses observed in the natural season than in the PCC, resulting
      in the identification of distinct PCC/natural season endophenotypes and a partial
      correlation between the TSSs recorded in the natural season versus those recorded
      in the PCC (r = 0.34, 0.54, and 0.65 for VLO(+), MC(+), and ragweed-positive
      participants, respectively). CONCLUSIONS: Prepriming in the natural pollinating
      season might obscure the true correlation between AR severity in the natural
      season versus the PCC. By mitigating confounding cofactors, PCC exposures have
      utility for evaluation of novel AR therapeutics.

PMID- 24331378
TI  - Why are direct comparisons of subcutaneous and sublingual immunotherapy so rare?

PMID- 24331379
TI  - Survey on retransplantation criteria for patients with severe combined
      immunodeficiency.

PMID- 24331380
TI  - Lesson from hypomorphic recombination-activating gene (RAG) mutations: Why
      asymptomatic siblings should also be tested.

PMID- 24331383
TI  - Changing healthcare laws and their impact on US allergy-immunology practice.

PMID- 24331381
TI  - Transcutaneous yellow fever vaccination of subjects with or without atopic
      dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease with a
      global prevalence ranging from 3% to 20%. Patients with AD have an increased risk
      for complications after viral infection (eg, herpes simplex virus), and
      vaccination of patients with AD with live vaccinia virus is contraindicated
      because of a heightened risk of eczema vaccinatum, a rare but potentially lethal
      complication associated with smallpox vaccination. OBJECTIVE: We sought to
      develop a better understanding of immunity to cutaneous viral infection in
      patients with AD. METHODS: In a double-blind randomized study we investigated the
      safety and immunogenicity of live attenuated yellow fever virus (YFV) vaccination
      of nonatopic subjects and patients with AD after standard subcutaneous
      inoculation or transcutaneous vaccination administered with a bifurcated needle.
      Viremia, neutralizing antibody, and antiviral T-cell responses were analyzed for
      up to 30 days after vaccination. RESULTS: YFV vaccination administered through
      either route was well tolerated. Subcutaneous vaccination resulted in higher
      seroconversion rates than transcutaneous vaccination but elicited similar
      antiviral antibody levels and T-cell responses in both the nonatopic and AD
      groups. After transcutaneous vaccination, both groups mounted similar
      neutralizing antibody responses, but patients with AD demonstrated lower
      antiviral T-cell responses by 30 days after vaccination. Among transcutaneously
      vaccinated subjects, a significant inverse correlation between baseline IgE
      levels and the magnitude of antiviral antibody and CD4(+) T-cell responses was
      observed. CONCLUSIONS: YFV vaccination of patients with AD through the
      transcutaneous route revealed that high baseline IgE levels provide a potential
      biomarker for predicting reduced virus-specific immune memory after
      transcutaneous infection with a live virus.

PMID- 24331384
TI  - Revisiting fatal asthma.

PMID- 24331385
TI  - The Patient Protection and Affordable Care Act: causes and effects.

PMID- 24331386
TI  - Asthma adherence: how can we help our patients do it better?

PMID- 24331387
TI  - Approach to desensitization in aspirin-exacerbated respiratory disease.

PMID- 24331388
TI  - Characterization of reactive nitrogen species in allergic asthma.
AB  - OBJECTIVE: To investigate the molecular mechanism of reactive nitrogen species
      (RNS) in the pathogenesis of asthma and examine the use of fractional exhaled
      nitric oxide (FENO) measurements in close conjunction with standard clinical
      assessments of asthma. DATA SOURCES: Through PubMed, Google Scholar, and Medline
      databases, a broad medical literature review was performed in the following areas
      of asthma pathobiology and management: allergic asthma, RNS, nitric oxide (NO),
      airway inflammation, and FENO. STUDY SELECTIONS: Studies were selected based on
      the physiologic and pathophysiologic roles of RNS in relation to allergic asthma.
      Current evaluations on clinical applications of FENO in asthma treatment also
      were selected. RESULTS: At the onset of an asthma attack, an enhanced production
      of NO strongly correlates with increase inducible NO synthase (NOS) activity,
      whereas endothelial NOS and neuronal NOS regulate primarily normal metabolic
      functions in the central and peripheral airways. During allergic inflammatory
      responses, NO and superoxide form peroxynitrite, which has deleterious effects in
      the respiratory tract. RNS directly accentuates airway inflammation and
      cytotoxicity through nitrosative stress. Moreover, the use of FENO to monitor
      eosinophilic-mediated airway inflammation is a potentially valuable assessment
      that supplements standard procedures to monitor the progression of asthma.
      CONCLUSION: This review examines recent evidence implicating the molecular
      mechanisms of NO and NO-derived RNS in the pathobiology of asthma and suggests
      that monitoring FENO may markedly contribute to asthma diagnosis.

PMID- 24331389
TI  - Interleukin-18 expression, CD8(+) T cells, and eosinophils in lungs of nonsmokers
      with fatal asthma.
AB  - BACKGROUND: The process of airway inflammation in the lungs of nonsmokers who die
      of asthma (fatal asthma) has not been reported in detail. OBJECTIVE: To examine
      nonsmokers who had died of asthma to exclude chronic obstructive pulmonary
      disease and investigate pulmonary inflammatory cells and the expression of
      interleukin-18 (IL-18) and its receptor in lung tissues compared with those in
      patients with well-controlled mild asthma and nonsmokers. METHODS: Lung tissues
      were obtained at autopsy examination from 12 nonsmokers with fatal asthma,
      excluding cases of chronic obstructive pulmonary disease, and from 5 nonsmokers
      with well-controlled mild asthma and 10 nonsmokers who had undergone surgical
      resection for lung cancer. Pulmonary inflammatory cells were examined and the
      expression of the proinflammatory cytokine IL-18 and its receptor in the lungs
      was evaluated. RESULTS: The numbers of eosinophils and lymphocytes, but not
      basophils or macrophages, were significantly increased in the lungs of patients
      with fatal asthma compared with the other 2 groups. The lung neutrophil count did
      not differ significantly between the fatal and mild asthma groups but was
      significantly higher in the fatal asthma group than in nonsmokers. CD8(+) T
      cells, but not CD4(+) T cells, were significantly increased in the lungs of the
      fatal asthma group compared with the other 2 groups. IL-18 protein and IL-18
      receptor were strongly expressed in the lungs in the fatal asthma group.
      CONCLUSION: Caspase-1 inhibitors, anti-IL-18 antibodies, anti-IL-18 receptor
      antibodies, IL-18 binding protein, or inhibitors of genes downstream of the IL-18
      signal transduction pathway may be of clinical benefit for the treatment of
      patients with severe asthma.

PMID- 24331390
TI  - Heliox-driven beta2-agonists nebulization for children and adults with acute
      asthma: a systematic review with meta-analysis.
AB  - BACKGROUND: The effect of heliox as a nebulizer beta2-agonist driving gas in
      acute asthma remains controversial. OBJECTIVE: To perform a systematic review
      with a meta-analysis of randomized trials designed to evaluate the efficacy of
      heliox versus oxygen in driving beta2-agonist nebulization in patients with acute
      asthma. METHODS: A search was conducted of all randomized controlled trials
      published before August 2013. Primary outcomes were change in spirometric
      measurements and severity composite score (pediatric studies); secondary outcomes
      were hospitalizations and serious adverse effects. RESULTS: Eleven trials from 10
      studies (697 participants) met the inclusion criteria (7 included adults and 3
      included children). The mean duration of heliox therapy was 120 minutes and the
      most common helium-oxygen mixture used was 70:30. Patients receiving heliox
      presented a statistically significant difference for mean percentage of change in
      peak expiratory flow (17.2%; 95% confidence interval 5.2-29.2, P = .005). Post
      hoc subgroup analysis showed that patients with severe and very severe asthma
      showed a significant improvement in peak expiratory flow compared with those with
      mild to moderate acute asthma. Heliox-driven nebulization also produced
      significant decreases in the risk of hospitalizations (odds ratio 0.49, 95%
      confidence interval 0.31-0.79, P = .003) and severity of exacerbations (pediatric
      studies; standard mean difference -0.74, 95%% confidence interval -1.45 to -0.03,
      P = .04). There were no group differences for serious adverse effects.
      CONCLUSION: This review suggests that heliox benefits in airflow limitation and
      hospital admissions could be considered clinically significant. Data support the
      use of heliox as a nebulizing beta2-agonist driving gas in the routine care of
      patients with acute asthma.

PMID- 24331391
TI  - Young, African American adults with asthma: what matters to them?
AB  - BACKGROUND: Asthma is a common chronic condition that shows significant health
      disparities among minority populations. Little research has focused on the
      management needs and preferences of young African American adults with asthma, a
      population undergoing dramatic life changes as they transition from adolescence
      to adulthood. OBJECTIVE: To understand the experiences and perspectives of young
      African American adults managing their asthma. METHODS: Focus groups were
      conducted with African American adults (n = 34) 18 to 30 years old with a
      physician diagnosis of asthma. Focus group sessions were audiotaped, transcribed
      verbatim, and coded using constant comparative analysis. RESULTS: Six major
      domains were identified and some of the salient themes included changes in asthma
      management needs with the onset of adulthood, career limitations owing to asthma,
      childcare interference with asthma regimen adherence, and difficulties with
      medication cost owing to lapses in insurance coverage. Participants also reported
      feeling discouraged when interacting with physicians as it related to their
      asthma care; yet ageism and racism were not perceived. Despite poor medication
      regimen compliance, participants were overwhelmingly interested in participating
      in asthma self-management programs and had strong preferences that such programs
      be tailored specifically to young adults with special consideration of the
      cultural experience of young African Americans with asthma. CONCLUSION: Young
      African American adults have specific barriers to optimal asthma care and
      distinctive ideas for self-management programs. It is important for the asthma
      care provider to identify and address these population- and age-specific barriers
      to improve asthma outcomes and decrease health care disparities.

PMID- 24331392
TI  - Trigeminal nerve stimulation triggers oral mast cell activation and vascular
      permeability.
AB  - BACKGROUND: The nervous system contributes to the pathophysiology of allergic and
      inflammatory diseases, including oral inflammation. Mast cells (MCs) are involved
      in their pathogenesis through proinflammatory mediator release. OBJECTIVE: To
      investigate the effect of trigeminal nerve (TN) stimulation compared with sham
      operation on MC activation and oral vascular permeability in the gingiva, palate,
      buccal mucosa, and tongue of the rat and to examine the possible role of
      substance P using rats treated with capsaicin as neonates to deplete substance P.
      METHODS: Six male Sprague-Dawley rats (250 g) were anesthetized and injected
      intravenously with Evans Blue (EB). Six other rats were injected neonatally with
      capsaicin (n = 3) or solvent (n = 3) and then injected with EB when they reached
      250 g. The mandibular branch of the TN was stimulated for 1 minute (n = 3), and
      the remaining rats (n = 3) were subjected to sham operation. The ipsilateral and
      contralateral sides of the mouth were examined for EB extravasation, and tissue
      sections were removed for light and electron microscopy. RESULTS: TN stimulation
      resulted in EB extravasation in the ipsilateral side compared with the
      contralateral side or the ipsilateral side of sham-operated rats. Significant
      degranulation of MCs also was evident only on the ipsilateral side (P < .0001).
      There was no difference in MC degranulation between the vehicle- and capsaicin
      treated rats, implying that neuropeptides other than substance P may be involved.
      CONCLUSION: This is the first time that TN stimulation has been shown to result
      in MC activation and oral vascular permeability, suggesting that MC inhibitors
      may be used for the treatment of oral inflammatory diseases.

PMID- 24331393
TI  - Occupational asthma, rhinitis, and contact urticaria caused by oxidative hair
      dyes in hairdressers.
AB  - BACKGROUND: Oxidative hair dyes commonly contain paraphenylene diamine (PPD) and
      its derivatives, a well-known cause of delayed hypersensitivity among both
      consumers and hairdressers. They are also considered possible causes of
      occupational respiratory diseases. Despite the widespread use of hair dyes, there
      are only a few reports of asthma, rhinitis, and contact urticaria caused by PPD
      and related compounds. OBJECTIVE: To characterize patients with occupational
      asthma, rhinitis, or contact urticaria associated with oxidative hair dyes and to
      evaluate the diagnostic methods. METHODS: We reviewed the patient files of the
      Finnish Institute of Occupational Health for the period January 1, 2001, through
      May 31, 2011, to identify patients diagnosed as having asthma, rhinitis, or
      contact urticaria associated with oxidative hair dyes. The diagnoses of asthma
      and rhinitis were based on specific inhalation challenges with hair dye products.
      Skin prick tests were performed with hair dye ingredients as hapten conjugates of
      human serum albumin and with hair dye products and ingredients as is. Open skin
      tests confirmed the diagnosis of contact urticaria. RESULTS: We describe 11
      hairdressers with occupational asthma (5 cases), rhinitis (5 cases), and contact
      urticaria (3 cases) due to hair dyes. Of the 52 specific inhalation challenges
      performed, 9 (17%) had positive results. One patient who experienced an
      anaphylactic reaction when having her own hair dyed had positive skin prick test
      results to PPD and toluene-2,5-diamine sulfate. CONCLUSION: Hairdressers are at
      risk for occupational asthma, rhinitis, and contact urticaria due to oxidative
      hair dyes. Skin prick testing may be insensitive for detecting immediate
      hypersensitivity to PPD and related compounds.

PMID- 24331394
TI  - Special consideration is required for the component-resolved diagnosis of egg
      allergy in infants.
AB  - BACKGROUND: There are few reports regarding differences in reactivity to the
      major egg allergens according to children's age, although component-resolved
      diagnosis is gradually being used. OBJECTIVE: To investigate differences in
      reactivity to major egg allergens among various age groups of children with egg
      allergy. METHODS: Twenty-seven patients diagnosed with egg allergy were included.
      Egg allergy was defined as a convincing history of reproducible symptoms within 2
      hours of egg consumption and an egg white-specific IgE level of at least 0.35
      kUA/L. Patients were divided into 3 age groups: younger than 12 months (group A,
      7 subjects), 12 to 23 months (group B, 8 subjects), and at least 24 months (group
      C, 12 subjects). Immunoblotting and enzyme-linked immunosorbent assay
      investigated IgE reactivity toward ovalbumin, ovomucoid, and ovotransferrin in
      eggs. RESULTS: Immunoblotting analysis showed that all patients in group A
      reacted to ovalbumin, whereas reactions to other proteins were not detected. All
      patients in group B displayed a reaction to ovalbumin and ovomucoid. IgE binding
      to ovotransferrin was shown in 3 patients in group B. All patients in group C
      displayed reactivity to ovalbumin, 5 patients showed a reaction to ovomucoid, and
      8 patients displayed a reaction to ovotransferrin. As a patient's age increased,
      specific IgE binding to ovalbumin and ovotransferrin increased (P = .011 and
      .004). CONCLUSION: IgE reactivity to egg allergens differs according to
      children's ages.

PMID- 24331395
TI  - Clinical predictors for favorable outcomes in an oral immunotherapy program for
      IgE-mediated cow's milk allergy.
AB  - BACKGROUND: Avoidance strategies in patients with cow's milk allergy occasionally
      fail to protect these patients from inadvertent exposures, leading to life
      threatening reactions. OBJECTIVE: To assess the safety and efficacy of milk oral
      immunotherapy as an alternative therapeutic strategy. METHODS: Patients (n = 280,
      >4 years old) with IgE-mediated cow's milk allergy were enrolled into a milk oral
      immunotherapy program at a single hospital center. High-risk patients were not
      excluded. The treatment protocol consisted of 3 rounds of oral induction
      performed every 4 weeks. On day 1, a patient's reaction threshold was determined.
      On days 2 and 3, a tolerated starting dose below the threshold was confirmed. Day
      4 mimicked the home treatment, which continued until the next induction. RESULTS:
      The median initial starting dose was 52.5 mg of cow's milk protein. Excluding
      those whose treatment failed in the first week (n = 5) or are still undergoing
      treatment (n = 15), 61.5% (160 of 260 patients) achieved 7,200 mg and 85.4% of
      patients were consuming at least 180 mg of milk protein. Reactions at home
      requiring the use of injectable epinephrine occurred in 15.7% of patients (44 of
      280) and in 0.075% (58 of 77,098) of doses administered. Predictors for achieving
      a full dose in multivariate analysis included a starting dose higher than 30 mg
      of milk protein (odds ratio 4.6, P < .001), not requiring epinephrine during
      induction (odds ratio 5.2, P < .001) or home treatment (odds ratio 2.6, P =
      .037), and the lack of nonanaphylactic type symptoms (odds ratio 15.6, P < .001).
      CONCLUSION: Milk oral immunotherapy, carried out in a highly controlled setting,
      is successful in protecting the overwhelming majority of patients from accidental
      exposures to cow's milk protein.

PMID- 24331396
TI  - Efficacy and safety of sulfasalazine in patients with chronic idiopathic
      urticaria.
AB  - BACKGROUND: There are limited data regarding alternative treatments for
      antihistamine refractory chronic idiopathic urticaria (CIU). Patients with
      recalcitrant skin disease often cannot gain satisfactory symptom control with
      standard therapies and may require prolonged courses of oral corticosteroids.
      There is a lack of information describing the degree and duration of
      sulfasalazine's efficacy, the frequency and nature of adverse reactions, and the
      appropriate safety monitoring parameters. OBJECTIVE: To present a case series
      detailing the efficacy and safety of sulfasalazine therapy in patients with CIU.
      METHODS: A retrospective chart review was conducted of 39 patients with
      sulfasalazine-treated CIU evaluated at Johns Hopkins Asthma and Allergy Center
      from October 2007 to March 2012. Eight patients were excluded from the final
      analysis. RESULTS: Twenty-six patients (83.9%) showed an improvement in symptoms
      within the first 3 months, with 51.6% of patients (n = 16) becoming asymptomatic
      within the first 6 months of starting sulfasalazine. Eleven patients (35.4%)
      achieved complete relief of symptoms after tapering off sulfasalazine therapy.
      Five of the 31 patients (16.1%) failed treatment, defined as worsening symptoms
      and pursuit of an alternative therapy. Six of 31 patients (19.4%) had a modified
      course of sulfasalazine therapy owing to abnormal hematologic parameters. Serious
      adverse events leading to drug discontinuation occurred in 6.5% of patients (n =
      2) and included a patient with drug-induced leukopenia and one with
      rhabdomyolysis. CONCLUSION: Sulfasalazine is a highly effective treatment for
      patients with antihistamine resistant CIU. The frequency of adverse events
      leading to an alteration of sulfasalazine treatment supports the need for close
      monitoring of these patients.

PMID- 24331397
TI  - Successful desensitization to agalsidase beta after anaphylaxis.

PMID- 24331398
TI  - Spice allergies in children.

PMID- 24331399
TI  - X-linked agammaglobulinemia presenting as polymicrobial pneumonia, including
      Pneumocystis jirovecii.

PMID- 24331400
TI  - Clinical assessment of allergen immunotherapy with differing doses of horse
      extract.

PMID- 24331401
TI  - Allergy products traded on eBay, 2007-2012.

PMID- 24331402
TI  - Puberty and asthma in a cohort of Swedish children.

PMID- 24331403
TI  - A retrospective review of veterans' adherence to allergen immunotherapy over 10
      years.

PMID- 24331404
TI  - Anaphylaxis associated with streptomycin skin testing.

PMID- 24331405
TI  - Allergen of the month-Melaleuca.

PMID- 24331406
TI  - Epidemiological and bacteriological profiles in children with burns.
AB  - OBJECTIVES: The aim of our study is to determine the most prevalent bacteria
      responsible for nosocomial infection (NI) in burned children. MATERIALS AND
      METHODS: A prospective analytic study was conducted over a period of 30 months at
      the Children's Hospital of Tunisia. All burned children were enrolled. RESULTS: A
      total of 185 children were hospitalised during the study period. The mean age was
      30 months (interquartile range, IR:18; 48). The gender ratio of the study
      population was 1.3 (104 males and 81 females). The mean total body surface area
      burned (TBSA) was 10% (IR:6; 16). The incidence rate of NI was 39.1 NIs per 1000
      patient-days and two-thirds of the infections were polymicrobial. The most common
      isolated micro-organisms were methicillin-susceptible Staphylococcus aureus
      (MSSA, 57.7%), wild-type Pseudomonas aeruginosa (35.9%) and wild-type
      Enterobacter cloacae (26.9%). The case fatality rate was 5.9% corresponding to a
      crude death rate of 1.32 deaths per year. Septic shock with multiple organ
      failure was the leading cause of death. CONCLUSION: The most common micro
      organisms responsible for NI in our series were of the wild-type phenotype. Thus,
      on suspicion of sepsis, empiric antibiotic treatment combining piperacillin,
      oxacillin and gentamicin can be proposed until identification of the causative
      microorganism is available.

PMID- 24331407
TI  - Gene expression profile of cytokines and receptors of inflammation from cultured
      keratinocytes of burned patients.
AB  - INTRODUCTION: At all stages of wound healing, growth factors and cytokines play a
      particularly important role in the interaction with keratinocytes cellular
      receptors. Keratinocytes have received little attention about their potential to
      act as a source and target of cytokines. Changes in the cytokine levels after the
      burning occur prior to the metabolic abnormalities. Thus, it may be possible to
      develop therapeutic interventions that can mitigate the acute inflammatory
      response and modulating expression of these cytokines. The objective was to
      evaluate the expression of 84 genes mediators of the inflammatory response by
      using PCR array in a primary human epidermal cultured keratinocytes from patients
      with burns. METHODS: Keratinocytes cultured from normal skin around injury from
      small and large burn patient were treated for DNA synthesis. The samples were
      analyzed by the PCR Superarray((r)) assay and curve analyses were performed for
      84 relevant human genes and their involvement in the inflammatory cytokines
      pathway and receptors. These genes were checked for the up or down regulation.
      And it was used MetaCoreTM for the analysis of networks and Gene Ontology (GO)
      processes. RESULTS: Chemokines of the CXC family were more expressed in the large
      burn group, except CXCL12. The C, CC and CX3C chemokine family were
      downregulated, especially in the small burn group. The interleukins IL8 and IL1B
      were more expressed in large burn than in small burn; except IL13RA1, IL13 and
      IL5RA that were downregulated, mainly in the small burn group. CONCLUSIONS: The
      cytokine profile showed some important differences between the large and small
      burn patients, and from this original database, we can create new interventional
      trials in acute inflammation in burns.

PMID- 24331408
TI  - A systematic review of the literature to support an evidence-based precepting
      program.
AB  - AIM: To provide a systematic review of the literature regarding development of an
      evidence-based Precepting Program for nurses transitioning to burn specialty
      practice. BACKGROUND: Burned patients are admitted to specialty Burn Centers
      where highly complex nursing care is provided. Successful orientation and
      integration into such a specialized work environment is a fundamental component
      of a nurse's ability to provide safe and holistic patient care. DESIGN: A
      systematic review of the literature was performed for the period 1995-2011 using
      electronic databases within PUBMED and Ovid search engines. DATA SOURCES:
      Databases included Medline, CINHAL, ProQuest for Dissertations and Thesis, and
      Cochran Collaboration using key search terms: preceptor, preceptee,
      preceptorship, precept*, nurs*, critical care, personality types, competency
      based education, and learning styles. REVIEW METHODS: Nurses graded the level and
      quality of evidence of the included articles using a modified 7-level rating
      system and the Johns Hopkins Nursing Quality of Evidence Appraisal during journal
      club meetings. RESULTS: A total of 43 articles related to competency (n=8),
      knowledge acquisition and personality characteristics (n=8), learning style
      (n=5), preceptor development (n=7), and Precepting Programs (n=14). CONCLUSIONS:
      A significant clinical gap existed between the scientific evidence and actual
      precepting practice of experienced nurses at the Burn Center. Based on this
      extensive review of the literature, it was determined that a sufficient evidence
      base existed for development of an evidence-based Precepting Program.

PMID- 24331409
TI  - KRAS mutations in non-small-cell lung cancer and colorectal cancer: implications
      for EGFR-targeted therapies.
AB  - BACKGROUND: KRAS mutations are associated with diverse biologic functions as well
      as prognostic and predictive impact in non-small cell-lung cancer (NSCLC) and
      colorectal cancer (CRC). In CRC, benefit from monoclonal antibody therapies
      targeting EGFR is generally limited to patients whose tumors have wild-type (WT)
      KRAS, whereas data suggest that this association is not present for NSCLC. We
      hypothesized that the unique tobacco-related carcinogenesis of NSCLC results in a
      divergence of KRAS MT genotype compared with CRC, contributing to differences in
      outcomes from EGFR-targeted therapies. MATERIAL AND METHODS: Tumor from 2603
      patients (838 CRC and 1765 NSCLC) was analyzed for KRAS mutations. DNA was
      extracted from microdissected formalin-fixed-paraffin-embedded specimens (FFPE)
      and 7 different base substitutions in codons 12 and 13 of KRAS were determined.
      RESULTS: KRAS mutation genotype differed significantly between NSCLC and CRC in
      frequency (25% vs. 39%; p<0.001), smoking-associated G>T transversions (73%
      versus 27%; p<0.001), and ratio of transversions to transitions (3.5 vs. 0.79;
      p<0.001). In NSCLC GLY12Cys mutations, resulting from a codon 12 GGT>TGT
      substitution, were observed in 44% compared to 10% for CRC. In contrast, codon 12
      or 13 GLY>ASP substitutions (resulting in a G>A transition) were more frequent in
      CRC (42%) compared with NSCLC (21%). CONCLUSION: In this large dataset, KRAS
      mutation patterns are quantitatively and qualitatively distinct between NSCLC and
      CRC, reflecting in part differences in tobacco-related carcinogenesis. In light
      of differences in predictive value for EGFR-directed monoclonal antibody therapy
      and prognosis for specific KRAS mutations between NSCLC and CRC, these data
      provide an underlying biologic rationale.

PMID- 24331410
TI  - Activation of Akt involves resistance to NF-kappaB inhibition and abrogation of
      both triggers synergistic apoptosis in lung adenocarcinoma cells.
AB  - OBJECTIVES: Although nuclear factor (NF)-kappaB and phosphoinositide 3-kinase
      (PI3K)-Akt-mTOR comprise key pathways, their interrelationship in lung cancer
      cell survival is poorly understood and needs further analyses. MATERIALS AND
      METHODS: We examined the activation of the NF-kappaB and Akt-mTORC1-p70 S6 kinase
      (S6K) pathways and the effect of inhibitors for NF-kappaB, mTORC1, and Akt using
      fresh lung adenocarcinoma cells. RESULTS: The cases used for this study showed
      constitutive NF-kappaB activity; however, all cases but one showed resistance to
      NF-kappaB inhibition. Further examination revealed that the resistant cases were
      also active in the Akt-mTORC1-S6K pathway. These cases were insensitive to mTORC1
      inhibition but sensitive to Akt inhibition. Akt inhibition recovered sensitivity
      to NF-kappaB inhibition and dual inhibition showed a synergistic effect on
      apoptosis induction. CONCLUSION: These results indicate that the activation of
      Akt involves resistance to NF-kappaB inhibition and both pathways synergistically
      support the survival of lung adenocarcinoma cells. The results also indicate that
      inhibition of the mTORC1-S6K pathway does not inhibit the survival of these
      cells.

PMID- 24331411
TI  - MiR-21 overexpression is associated with acquired resistance of EGFR-TKI in non
      small cell lung cancer.
AB  - BACKGROUND AND PURPOSE: With the increasing use of epidermal growth factor
      receptor tyrosine kinase inhibitor (EGFR TKI) in patients with advanced non-small
      cell lung cancer (NSCLC), its acquired resistance has become a major clinical
      problem. Recent studies revealed that miR-21 was involved into the resistance of
      cytotoxic agents. The aim of this study was to investigate its role in the
      acquired resistance of NSCLC to EGFR-TKI. METHODS: EGFR-TKI-sensitive human lung
      adenocarcinoma cell line PC9 and the acquired resistant cell line, PC9R, were
      used. Lentiviral vectors were used to infect PC9 or PC9R to regulate the miR-21
      expression. The expression of targeted proteins PTEN and PDCD4 was controlled by
      RNA interference. MicroRNA array, RT-PCR and TaqMan MicroRNA Assays were used to
      detect miR-21 expression. The MTT and Annexin V assays were used to determine
      proliferation and apoptosis. Western Blot and immunohistochemistry were used to
      analyze target protein expression (PTEN, PDCD4, Akt, p-Akt). We also constructed
      PC9R xenograft tumor model to observe the relationship between miR-21 and EGFR
      TKI resistance in vivo and validated it in the clinical serum specimens of NSCLC
      patients treated with EGFR-TKI. RESULT: MiR-21 was overexpressed in the EGFR-TKI
      resistant cell line PC9R relative to PC9. The level of miR-21 was reversely
      correlated with the expression of PTEN and PDCD4 and positive correlated with
      PI3K/Akt pathway. Inhibiting miR-21 with lentivirus vector induces apoptosis in
      PC9R cell line and inhibiting miR-21with ASO suppressed tumor growth in nude mice
      treated with EGFR-TKI. Furthermore, serum miR-21 expression in NSCLC patients
      treated with EGFR-TKI was significantly higher at the time of acquiring
      resistance than at baseline (p<0.01). CONCLUSION: miR-21 is involved in acquired
      resistance of EGFR-TKI in NSCLC, which is mediated by down-regulating PTEN and
      PDCD4 and activating PI3K/Akt pathway.

PMID- 24331412
TI  - Effect of infliximab on male fertility: Comment on the article "Fertility in male
      patients with seronegative spondyloarthropathies treated with infliximab" by
      Saougou et al., Joint Bone Spine 2013;80, 34-37.

PMID- 24331413
TI  - Hydrogen-rich water regulates cucumber adventitious root development in a heme
      oxygenase-1/carbon monoxide-dependent manner.
AB  - Hydrogen gas (H2) is an endogenous gaseous molecule in plants. Although its
      reputation is as a "biologically inert gas", recent results suggested that H2 has
      therapeutic antioxidant properties in animals and plays fundamental roles in
      plant responses to environmental stresses. However, whether H2 regulates root
      morphological patterns is largely unknown. In this report, hydrogen-rich water
      (HRW) was used to characterize H2 physiological roles and possible signaling
      transduction pathways in the promotion of adventitious root (AR) formation in
      cucumber explants. Our results showed that a 50% concentration of HRW was able to
      mimic the effect of hemin, an inducer of a carbon monoxide (CO) synthetic enzyme,
      and heme oxygenase-1 (HO-1), in restoring AR formation in comparison with the
      inhibition effect conferred by auxin-depletion treatment alone. It was further
      shown that the inducible effect of HRW could be further blocked by the co
      treatment with N-1-naphthylphtalamic acid (NPA; an auxin transport inhibitor).
      The HRW-induced response, at least partially, was HO-1-dependent. This conclusion
      was supported by the fact that the exposure of cucumber explants to HRW up
      regulates cucumber HO-1 gene expression and its protein levels. HRW-mediated
      induction of representative target genes related to auxin signaling and AR
      formation, such as CsDNAJ-1, CsCDPK1/5, CsCDC6, CsAUX22B-like, and CsAUX22D-like,
      and thereafter AR formation (particularly in the AR length) was differentially
      sensitive to the HO-1 inhibitor zinc protoporphyrin IX (ZnPP). Above blocking
      actions were clearly reversed by CO, further confirming that the above response
      was HO-1/CO-specific. However, the addition of a well-known antioxidant, ascorbic
      acid (AsA), failed to influence AR formation triggered by HRW, thus ruling out
      the involvement of redox homeostasis in this process. Together, these results
      indicated that HRW-induced adventitious rooting is, at least partially,
      correlated with the HO-1/CO-mediated responses. We also suggested that exogenous
      HRW treatment on plants might be a good option to induce root organogenesis. 

PMID- 24331414
TI  - Phosphorus deficiency enhances aluminum tolerance of rice (Oryza sativa) by
      changing the physicochemical characteristics of root plasma membranes and cell
      walls.
AB  - The negative charge at the root surface is mainly derived from the phosphate
      group of phospholipids in plasma membranes (PMs) and the carboxyl group of
      pectins in cell walls, which are usually neutralized by calcium (Ca) ions
      contributing to maintain the root integrity. The major toxic effect of aluminum
      (Al) in plants is the inhibition of root elongation due to Al binding tightly to
      these negative sites in exchange for Ca. Because phospholipid and pectin
      concentrations decrease in roots of some plant species under phosphorus (P)
      limiting conditions, we hypothesized that rice (Oryza sativa L.) seedlings grown
      under P-limiting conditions would demonstrate enhanced Al tolerance because of
      their fewer sites on their roots. For pretreatment, rice seedlings were grown in
      a culture solution with (+P) or without (-P) P. Thereafter, the seedlings were
      transferred to a solution with or without Al, and the lipid, pectin,
      hemicellulose, and mineral concentrations as well as Al tolerance were then
      determined. Furthermore, the low-Ca tolerance of P-pretreated seedlings was
      investigated under different pH conditions. The concentrations of phospholipids
      and pectins in the roots of rice receiving -P pretreatment were lower than those
      receiving +P pretreatment. As expected, seedlings receiving the -P pretreatment
      showed enhanced Al tolerance, accompanied by the decrease in Al accumulation in
      their roots and shoots. This low P-induced enhanced Al tolerance was not
      explained by enhanced antioxidant activities or organic acid secretion from roots
      but by the decrease in phospholipid and pectin concentrations in the roots. In
      addition, low-Ca tolerance of the roots was enhanced by the -P pretreatment under
      low pH conditions. This low P-induced enhancement of low-Ca tolerance may be
      related to the lower Ca requirement to maintain PM and cell wall structures in
      roots of rice with fewer phospholipids and pectins. 

PMID- 24331415
TI  - Osmotic stress responses of individual white oak (Quercus section, Quercus
      subgenus) genotypes cultured in vitro.
AB  - White oaks (Quercus section, Quercus subgenus) are widely distributed in Europe.
      Quercus petraea (sessile oak), an economically important species is predicted to
      be affected by climate change. Q. pubescens (pubescent oak) and Q. virgiliana
      (Italian pubescent oak) are economically less important, drought tolerant
      species. Frequent hybridization of white oaks was observed and currently the
      introgression of Q. pubescens and Q. virgiliana in non-mediterranean regions of
      Europe has been reported. Our goal was to use tissue cultures established from
      individual trees of the above taxa and their putative hybrids, all present in the
      forest stand of Sikfokut LTER Research Area (NE Hungary) as simple experimental
      model systems for studying drought/osmotic stress tolerance. Tissue cultures are
      more suitable models for such studies, than seedlings, because they are
      genetically identical to the parent plants. Polyethylene glycol (PEG6000)
      treatments were used for this purpose. The identification of taxa was based on
      leaf morphological traits and microsatellite analysis and showed that Q. petraea
      is genetically distinct to all other taxa examined. We established six callus
      lines of Quercus. As expected, in Q. petraea cultures PEG6000 induced severe loss
      of fresh weight and the ability to recover after removal of the osmoticum, which
      was not characteristic for Q. pubescens and Q. virgiliana. Putative hybrids
      exhibited an intermediate response to osmotic stress. Activity gels showed the
      increase of single-strand preferring (SSP) nuclease and no significant change of
      guaiacol-peroxidase activities in drought-sensitive genotypes/cultures and no
      significant increase of SSP nuclease activities accompanied with increases of
      guaiacol-peroxidase activities in drought-tolerant ones. This indicates that
      drought/osmotic stress tolerance is associated to increased capacity of
      scavenging reactive oxygen species and hence less susceptibility to DNA damage.
      Our results confirm that tissue cultures of oak are suitable model systems for
      studying drought/osmotic stress responses. 

PMID- 24331416
TI  - Identification of quantitative trait locus for abscisic acid responsiveness on
      chromosome 5A and association with dehydration tolerance in common wheat
      seedlings.
AB  - The phytohormone abscisic acid (ABA) plays important roles in response to
      environmental stress as well as in seed maturation and dormancy. In common wheat,
      quantitative trait loci (QTLs) for ABA responsiveness at the seedling stage have
      been reported on chromosomes 1B, 2A, 3A, 6D and 7B. In this study, we identified
      a novel QTL for ABA responsiveness on chromosome 5A using an F2 population
      derived from a cross between the common wheat cultivar Chinese Spring (CS) and a
      chromosome substitution line of CS with chromosome 5A of cultivar Hope (Hope5A).
      This QTL was found in a similar chromosomal region to previously reported QTLs
      for drought tolerance and seed dormancy. Physiological characterization of the
      QTL revealed a small effect on dehydration tolerance and seed dormancy. The rate
      of water loss from leaves during dehydration was lower, and transcript
      accumulation of the cold responsive (COR)/late embryogenesis abundant (LEA) genes
      Wrab18 and Wdhn13 tended to be higher under dehydration stress in F2 individuals
      carrying the Hope allele of the QTL, which also showed higher ABA responsiveness
      than the CS allele-carrying individuals. Seed dormancy of individuals carrying
      the Hope allele also tended to be lower than those carrying the CS allele. Our
      results suggest that variation in ABA responsiveness among common wheat cultivars
      is at least partly determined by the 5A QTL, and that this QTL contributes to
      development of dehydration and preharvest sprouting tolerance. 

PMID- 24331417
TI  - Catalase activity is modulated by calcium and calmodulin in detached mature
      leaves of sweet potato.
AB  - Catalase (CAT) functions as one of the key enzymes in the scavenging of reactive
      oxygen species and affects the H2O2 homeostasis in plants. In sweet potato, a
      major catalase isoform was detected, and total catalase activity showed the
      highest level in mature leaves (L3) compared to immature (L1) and completely
      yellow, senescent leaves (L5). The major catalase isoform as well as total
      enzymatic activity were strongly suppressed by ethylene glycol-bis(2
      aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). This inhibition could be
      specifically and significantly mitigated in mature L3 leaves by exogenous CaCl2,
      but not MgCl2 or CoCl2. EGTA also inhibited the activity of the catalase isoform
      in vitro. Furthermore, chlorpromazine (CPZ), a calmodulin (CAM) inhibitor,
      drastically suppressed the major catalase isoform as well as total enzymatic
      activity, and this suppression was alleviated by exogenous sweet potato
      calmodulin (SPCAM) fusion protein in L3 leaves. CPZ also inhibited the activity
      of the catalase isoform in vitro. Protein blot hybridization showed that both
      anti-catalase SPCAT1 and anti-calmodulin SPCAM antibodies detect a band at the
      same position, which corresponds to the activity of the major catalase isoform
      from unboiled, but not boiled crude protein extract of L3 leaves. An inverse
      correlation between the major catalase isoform/total enzymatic activity and the
      H2O2 level was also observed. These data suggest that sweet potato CAT activity
      is modulated by CaCl2 and SPCAM, and plays an important role in H2O2 homeostasis
      in mature leaves. Association of SPCAM with the major CAT isoform is required and
      regulates the in-gel CAT activity band. 

PMID- 24331418
TI  - Putrescine, a fast-acting switch for tolerance against osmotic stress.
AB  - During the last decade we showed clearly that abiotic stress changes the cellular
      composition of polyamines, which in turn regulate the photochemical and non
      photochemical quenching of the received light energy in the photosynthetic
      apparatus and that modulate substantially the level of plant tolerance. In the
      present contribution, we tried to change the bioenergetics of the leaf discs
      before the exposure to osmotic stress only by exogenously supplied putrescine, in
      order to enhance quickly the tolerance against the abiotic stress. Tobacco leaf
      discs treated with polyethylene-glycol reduced their water content about 24%
      within 1h. This relatively mild osmotic stress increased endogenous putrescine
      about 83% and decreased maximum photosystem II photochemical efficiency about
      14%. In line with this, here we show that treatment with 1mM exogenous putrescine
      1h before polyethylene-glycol addition protects the photochemical capacity and
      inhibits loss of water, confirming the key role of putrescine in the modulation
      of plant tolerance against osmotic stress. Furthermore, our recent works indicate
      that putrescine is accumulated in lumen during light reactions and may act as a
      permeable buffer and an osmolyte. 

PMID- 24331419
TI  - Hydrogen sulfide delays GA-triggered programmed cell death in wheat aleurone
      layers by the modulation of glutathione homeostasis and heme oxygenase-1
      expression.
AB  - Hydrogen sulfide (H2S) is considered as a cellular signaling intermediate in
      higher plants, but corresponding molecular mechanisms and signal transduction
      pathways in plant biology are still limited. In the present study, a combination
      of pharmacological and biochemical approaches was used to study the effect of H2S
      on the alleviation of GA-induced programmed cell death (PCD) in wheat aleurone
      cells. The results showed that in contrast with the responses of ABA, GA brought
      about a gradual decrease of l-cysteine desulfhydrase (LCD) activity and H2S
      production, and thereafter PCD occurred. Exogenous H2S donor sodium hydrosulfide
      (NaHS) not only effectively blocked the decrease of endogenous H2S release, but
      also alleviated GA-triggered PCD in wheat aleurone cells. These responses were
      sensitive to hypotaurine (HT), a H2S scavenger, suggesting that this effect of
      NaHS was in an H2S-dependent fashion. Further experiment confirmed that H2S,
      rather than other sodium- or sulphur-containing compounds derived from the
      decomposing of NaHS, was attributed to the rescuing response. Importantly, the
      reversing effect was associated with glutathione (GSH) because the NaHS triggered
      increases of endogenous GSH content and the ratio of GSH/oxidized GSH (GSSG) in
      GA-treated layers, and the NaHS-mediated alleviation of PCD was markedly
      eliminated by l-buthionine-sulfoximine (BSO, a selective inhibitor of GSH
      biosynthesis). The inducible effect of NaHS was also ascribed to the modulation
      of heme oxygenase-1 (HO-1), because the specific inhibitor of HO-1 zinc
      protoporphyrin IX (ZnPP) significantly suppressed the NaHS-related responses. By
      contrast, the above inhibitory effects were reversed partially when carbon
      monoxide (CO) aqueous solution or bilirubin (BR), two of the by-products of HO-1,
      was added, respectively. NaHS-triggered HO-1 gene expression in GA-treated layers
      was also confirmed. Together, the above results clearly suggested that the H2S
      delayed PCD in GA-treated wheat aleurone cells was associated with the modulation
      of GSH homeostasis and HO-1 gene expression. 

PMID- 24331420
TI  - Transport of flavonolignans to the culture medium of elicited cell suspensions of
      Silybum marianum.
AB  - Cell suspension cultures of Silybum marianum are able to excrete silymarin
      compounds into the medium upon elicitation with methyl jasmonate or
      cyclodextrins. Knowledge of transport mechanism is important to understand Sm
      metabolism and to develop strategies aimed at increasing production by means of
      cell cultures. For these reasons, a pharmacological approach was undertaken in
      this work in order to elucidate the possible mechanism involved in the release of
      this class of secondary metabolites into the extracellular medium of suspensions.
      Treatment with an ionophore or NH4Cl displayed little effect in elicited
      cultures, thus indicating that secondary transport, which uses electrochemical
      gradients, is not involved in the release. Several inhibitors of ABC transporters
      showed differential effects. Sodium ortho-vanadate, a typical suppressor of
      ATPase activity, was highly toxic to cultures even at very low concentrations.
      The common Ca-channel blocker verapamil did not influence extracellular secondary
      metabolite accumulation. Glybenclamide and probenecid, both effective inhibitors
      of ABCC-type ABC transporters, strongly reduced silymarin secretion. A partial
      cDNA, SmABC1, which showed similarity to ABCC-type ABC transporters, was isolated
      by RT-PCR from silymarin-producing cultures. SmABC1 expression was enhanced by
      methyljasmonate and cyclodextrins. Brefeldin A, a fungal metabolite which affects
      vesicular trafficking by preventing GTP/GDP exchange, inhibited release in a dose
      dependent manner. These results suggest that excretion of silymarin and their
      precursors is a transporter-dependent active transport and that yet another
      mechanism involving a vesicle trafficking system seems to participate in driving
      this class of secondary metabolites to the extracellular compartment. 

PMID- 24331421
TI  - Adaptation strategies of two closely related Desmodesmus armatus (green alga)
      strains contained different amounts of cadmium: a study with light-induced
      synchronized cultures of algae.
AB  - During the Desmodesmus armatus cell cycle, 8-celled coenobia of 276-4d strain
      accumulated a much lower amounts of cadmium than unicells of B1-76 strain.
      Cadmium reduced growth and photosynthesis in the cells of strain B1-76, but not
      those of 276-4d strain. Cells of 276-4d strain revealed a higher activity of
      superoxide dismutase (SOD) isoforms, in particular the activity and protein
      content of Fe-SOD. Cu/Zn-SOD was earlier and much stronger induced by cadmium in
      276-4d than in B1-76 strain, whereas Fe- and Mn-SOD activity and Fe-SOD synthesis
      were induced only in 276-4d strain. Cadmium did not affect the heat shock protein
      70 synthesis in B1-76 strain, but significantly stimulated this process in 276-4d
      strain. The level of glutathione increased 30-fold during cell development of Cd
      exposed 276-4d strain, while in B1-76 it increased about 12 timed. Matured cells
      of both strains exposed to cadmium produced comparable amounts of phytochelatins
      and other thiol peptides, but their production in young cells of B1-76 strain was
      much higher than in 276-4d strain. In conclusion, a complex of internal
      detoxification mechanisms appeared to be more efficient in cells of 276-4d strain
      than B1-76 one. 

PMID- 24331422
TI  - Involvement of peroxidase activity in developing somatic embryos of Medicago
      arborea L. Identification of an isozyme peroxidase as biochemical marker of
      somatic embryogenesis.
AB  - The legume Medicago arborea L. is very interesting as regards the regeneration of
      marginal arid soils. The problem is that it does not have a good germinative
      yield. It was therefore decided to regenerate via somatic embryogenesis and find
      a marker of embryogenic potential. In this study, peroxidase activity was
      evaluated in non-embryogenic and embryogenic calli from M. arborea L. A decrease
      in soluble peroxidase activity is observed in its embryonic calli at the time at
      which the somatic embryos begin to appear. This activity is always lower in
      embryonic calli than in non-embryonic ones (unlike what happens in the case of
      wall-bound peroxidases). These results suggest that peroxidases can be considered
      to be enzymes involved in somatic embryogenesis in M. arborea. In addition,
      isozyme analyses were carried out on protein extracts using polyacrylamide gel
      electrophoresis. The band called P5 was detected only in embryogenic cultures at
      very early stages of development. This band was digested with trypsin and
      analyzed using linear ion trap (LTQ) mass spectrometer. In P5 isoform a
      peroxidase-L-ascorbate peroxidase was identified. It can be used as a marker that
      allows the identification of embryological potential.

PMID- 24331423
TI  - Studies on the expression of linalool synthase using a promoter-beta
      glucuronidase fusion in transgenic Artemisia annua.
AB  - Artemisinin, an antimalarial endoperoxide sesquiterpene, is synthesized in
      glandular trichomes of Artemisia annua L. A number of other enzymes of terpene
      metabolism utilize intermediates of artemisinin biosynthesis, such as isopentenyl
      and farnesyl diphosphate, and may thereby influence the yield of artemisinin. In
      order to study the expression of such enzymes, we have cloned the promoter
      regions of some enzymes and fused them to beta-glucuronidase (GUS). In this
      study, we have investigated the expression of the monoterpene synthase linalool
      synthase (LIS) using transgenic A. annua carrying the GUS gene under the control
      of the LIS promoter. The 652bp promoter region was cloned by the genome walker
      method. A number of putative cis-acting elements were predicted indicating that
      the LIS is driven by a complex regulation mechanism. Transgenic plants carrying
      the promoter-GUS fusion showed specific expression of GUS in T-shaped trichomes
      (TSTs) but not in glandular secretory trichomes, which is the site for
      artemisinin biosynthesis. GUS expression was observed at late stage of flower
      development in styles of florets and in TSTs and guard cells of basal bracts. GUS
      expression after wounding showed that LIS is involved in plant responsiveness to
      wounding. Furthermore, the LIS promoter responded to methyl jasmonate (MeJA).
      These results indicate that the promoter carries a number of cis-acting
      regulatory elements involved in the tissue-specific expression of LIS and in the
      response of the plant to wounding and MeJA treatment. Southern blot analysis
      indicated that the GUS gene was integrated in the A. annua genome as single or
      multi copies in different transgenic lines. Promoter activity analysis by qPCR
      showed that both the wild-type and the recombinant promoter are active in the
      aerial parts of the plant while only the recombinant promoter was active in
      roots. Due to the expression in TSTs but not in glandular trichomes, it may be
      concluded that LIS expression will most likely have little or no effect on
      artemisinin production. 

PMID- 24331424
TI  - Organization of perinuclear actin in live tobacco cells observed by PALM with
      optical sectioning.
AB  - Actin performs a wide variety of different tasks. This functional diversity may
      be accomplished either by the formation of different isotypes or by suitable
      protein decoration that regulates structure and dynamics of actin filaments. To
      probe for such a potential differential decoration, the actin-binding peptide
      Lifeact was fused to different photoactivatable fluorescent proteins. These
      fusions were stably expressed in Nicotiana tabacum L. cv. Bright Yellow 2 cells
      to follow dynamic reorganization of the actin cytoskeleton during the cell cycle.
      The Lifeact-monomeric variant of IrisFP fusion protein was observed to
      indiscriminately label both, central and cortical, actin filaments, whereas the
      tetrameric Lifeact-photoswitchable red fluorescent protein fusion construct
      selectively labeled only a specific perinuclear sub-population of actin. By using
      photoactivated localization microscopy, we acquired super-resolution images with
      optical sectioning to obtain a 3D model of perinuclear actin. This novel approach
      revealed that the perinuclear actin basket wraps around the nuclear envelope in a
      lamellar fashion and repartitions toward the leading edge of the migrating
      nucleus. Based on these data, we suggest that actin that forms the perinuclear
      basket differs from other actin assemblies by a reduced decoration with actin
      binding proteins, which is consistent with the differential decoration model. 

PMID- 24331425
TI  - High temperatures limit plant growth but hasten flowering in root chicory
      (Cichorium intybus) independently of vernalisation.
AB  - An increase in mean and extreme summer temperatures is expected as a consequence
      of climate changes and this might have an impact on plant development in numerous
      species. Root chicory (Cichorium intybus L.) is a major crop in northern Europe,
      and it is cultivated as a source of inulin. This polysaccharide is stored in the
      tap root during the first growing season when the plant grows as a leafy rosette,
      whereas bolting and flowering occur in the second year after winter
      vernalisation. The impact of heat stress on plant phenology, water status,
      photosynthesis-related parameters, and inulin content was studied in the field
      and under controlled phytotron conditions. In the field, plants of the Crescendo
      cultivar were cultivated under a closed plastic-panelled greenhouse to
      investigate heat-stress conditions, while the control plants were shielded with a
      similar, but open, structure. In the phytotrons, the Crescendo and Fredonia
      cultivars were exposed to high temperatures (35 degrees C day/28 degrees C night)
      and compared to control conditions (17 degrees C) over 10 weeks. In the field,
      heat reduced the root weight, the inulin content of the root and its degree of
      polymerisation in non-bolting plants. Flowering was observed in 12% of the heat
      stressed plants during the first growing season in the field. In the phytotron,
      the heat stress increased the total number of leaves per plant, but reduced the
      mean leaf area. Photosynthesis efficiency was increased in these plants, whereas
      osmotic potential was decreased. High temperature was also found to induced
      flowering of up to 50% of these plants, especially for the Fredonia cultivar. In
      conclusion, high temperatures induced a reduction in the growth of root chicory,
      although photosynthesis is not affected. Flowering was also induced, which
      indicates that high temperatures can partly substitute for the vernalisation
      requirement for the flowering of root chicory. 

PMID- 24331426
TI  - Alkaloid metabolism in thrips-Papaveraceae interaction: recognition and mutual
      response.
AB  - Frankliniella occidentalis (Pergande), the Western Flower Thrips (WFT), is a
      polyphagous and highly adaptable insect of the order Thysanoptera. It has a broad
      host range but is rarely found on Papaveraceae, which might be due to deterrent
      effects of alkaloids present in most species of this family. In order to test the
      adaptive potential of WFT, we investigated its interaction with two Papaveraceae
      offered as sole feeding source. We found that WFT are able to live and feed on
      leaves of Eschscholzia californica and Chelidonium majus. Both plants respond to
      thrips feeding by the enhanced production of benzophenanthridine alkaloids.
      Furthermore, cell cultures of E. californica react to water insoluble compounds
      prepared from adult thrips with enhanced alkaloid production. During feeding, WFT
      take up benzophenanthridine alkaloids from either plant and from an artificial
      feeding medium and convert them to their less toxic dihydroderivatives. This was
      shown in detail with sanguinarine, the most cytotoxic benzophenanthridine. A
      similar conversion is used in plants to prevent self-intoxication by their own
      toxins. We conclude that WFT causes a phytoalexin-like response in Papaveraceae,
      but is able to adapt to such host plants by detoxification of toxic alkaloids. 

PMID- 24331427
TI  - Early cell-wall modifications of maize cell cultures during habituation to
      dichlobenil.
AB  - Studies involving the habituation of plant cell cultures to cellulose
      biosynthesis inhibitors have achieved significant progress as regards
      understanding the structural plasticity of cell walls. However, since habituation
      studies have typically used high concentrations of inhibitors and long-term
      habituation periods, information on initial changes associated with habituation
      has usually been lost. This study focuses on monitoring and characterizing the
      short-term habituation process of maize (Zea mays) cell suspensions to
      dichlobenil (DCB). Cellulose quantification and FTIR spectroscopy of cell walls
      from 20 cell lines obtained during an incipient DCB-habituation process showed a
      reduction in cellulose levels which tended to revert depending on the inhibitor
      concentration and the length of time that cells were in contact with it.
      Variations in the cellulose content were concomitant with changes in the
      expression of several ZmCesA genes, mainly involving overexpression of ZmCesA7
      and ZmCesA8. In order to explore these changes in more depth, a cell line
      habituated to 1.5MUM DCB was identified as representative of incipient DCB
      habituation and selected for further analysis. The cells of this habituated cell
      line grew more slowly and formed larger clusters. Their cell walls were modified,
      showing a 33% reduction in cellulose content, that was mainly counteracted by an
      increase in arabinoxylans, which presented increased extractability. This result
      was confirmed by immunodot assays graphically plotted by heatmaps, since
      habituated cell walls had a more extensive presence of epitopes for arabinoxylans
      and xylans, but also for homogalacturonan with a low degree of esterification and
      for galactan side chains of rhamnogalacturonan I. Furthermore, a partial shift of
      xyloglucan epitopes toward more easily extractable fractions was found. However,
      other epitopes, such as these specific for arabinan side chains of
      rhamnogalacturonan I or homogalacturonan with a high degree of esterification,
      seemed to be not affected. In conclusion, the early modifications occurring in
      maize cell walls as a consequence of DCB-habituation involved quantitative and
      qualitative changes of arabinoxylans, but also other polysaccharides. Thereby
      some of the changes that took place in the cell walls in order to compensate for
      the lack of cellulose differed according to the DCB-habituation level, and
      illustrate the ability of plant cells to adopt appropriate coping strategies
      depending on the herbicide concentration and length of exposure time. 

PMID- 24331428
TI  - Quantitative analysis of herbivore-induced cytosolic calcium by using a Cameleon
      (YC 3.6) calcium sensor in Arabidopsis thaliana.
AB  - Ca(2+) is a key player in plant cell responses to biotic and abiotic stress.
      Owing to the central role of cytosolic Ca(2+) ([Ca(2+)]cyt) during early
      signaling and the need for precise determination of [Ca(2+)]cyt variations, we
      used a Cameleon YC 3.6 reporter protein expressed in Arabidopsis thaliana to
      quantify [Ca(2+)]cyt variations upon leaf mechanical damage (MD), herbivory by
      3rd and 5th instar larvae of Spodoptera littoralis and S. littoralis oral
      secretions (OS) applied to MD. YC 3.6 allowed a clear distinction between MD and
      herbivory and discriminated between the two larvae instars. To our knowledge this
      is the first report of quantitative [Ca(2+)]cyt determination upon herbivory
      using a Cameleon calcium sensor. 

PMID- 24331429
TI  - Reduced mitochondrial and ascorbate-glutathione activity after artificial ageing
      in soybean seed.
AB  - The effect of artificial ageing on the relationship between mitochondrial
      activities and the antioxidant system was studied in soybean seeds (Glycine max
      L. cv. Zhongdou No. 27). Ageing seeds for 18d and 41d at 40 degrees C reduced
      germination from 99% to 52% and 0%, respectively. In comparison to the control,
      malondialdehyde content and leachate conductivity in aged seeds increased and
      were associated with membrane damage. Transmission electron microscopy and
      Percoll density gradient centrifugation showed that aged seeds mainly contained
      poorly developed mitochondria in which respiration and marker enzymes activities
      were significantly reduced. Heavy mitochondria isolated from the interface of the
      21% and 40% Percoll were analyzed. Mitochondrial antioxidant enzymes activities
      including superoxide dismutase, ascorbate peroxidase, glutathione reductase,
      monodehydroascorbate reductase, and dehydroascorbate reductase were significantly
      reduced in aged seeds. A decrease in total ascorbic acid (ASC) and glutathione
      (GSH) content as well as the reduced/oxidized ratio of ASC and GSH in
      mitochondria with prolonged ageing showed that artificial ageing reduced ASC-GSH
      cycle activity. These results suggested an elevated reactive oxygen species (ROS)
      level in the aged seeds, which was confirmed by measurements of superoxide
      radical and hydrogen peroxide levels. We conclude that mitochondrial dysfunction
      in artificially aged seeds is due to retarded mitochondrial and ASC-GSH cycle
      activity and elevated ROS accumulation. 

PMID- 24331430
TI  - Virus-induced gene silencing of PEAM4 affects floral morphology by altering the
      expression pattern of PsSOC1a and PsPVP in pea.
AB  - pea-MADS4 (PEAM4) regulates floral morphology in Pisum sativum L., however, its
      molecular mechanisms still remain unclear. Virus-induced gene silencing (VIGS) is
      a recently developed reverse genetic approach that facilities an easier and more
      rapid study of gene functions. In this study, the PEAM4 gene was effectively
      silenced by VIGS using a pea early browning virus (PEBV) in wild type pea JI992.
      The infected plants showed abnormal phenotypes, as the floral organs, especially
      the sepals and petals changed in both size and shape, which made the corolla less
      closed. The petals changed in morphology and internal symmetry with, the stamens
      reduced and carpel dehisced. Larger sepals and longer tendrils with small cauline
      leaves appeared, with some sepals turning into bracts, and secondary
      inflorescences with fused floral organs were formed, indicating a flower-to
      inflorescence change. The infected plants also displayed a delayed and prolonged
      flowering time. The PEAM4-VIGS plants with altered floral morphology were similar
      to the pim (proliferating inflorescence meristem) mutant and also mimicked the
      phenotypes of ap1 mutants in Arabidopsis. The expression pattern of the
      homologous genes PsSOC1a and PsSVP, which were involved in flowering time and
      florescence morphological control downstream of PEAM4, were analyzed by real-time
      RT-PCR and mRNA in situ hybridization. PsSOC1a and PsSVP were ectopically
      expressed and enhanced in the floral meristems from PEAM4-silenced plants. Our
      data suggests that PEAM4 may have a similar molecular mechanism as AtAP1, which
      inhibits the expression of PsSOC1a and PsSVP in the floral meristem from the
      early stages of flower development. As such, in this way PEAM4 plays a crucial
      role in maintaining floral organ identity and flower development in pea. 

PMID- 24331431
TI  - Rescue of heavy metal effects on cell physiology of the algal model system
      Micrasterias by divalent ions.
AB  - Recent studies have shown that metals such as copper, zinc, aluminum, cadmium,
      chromium, iron and lead cause severe dose-dependent disturbances in growth,
      morphogenesis, photosynthetic and respiratory activity as well as on
      ultrastructure and function of organelles in the algal model system Micrasterias
      denticulata (Volland et al., 2011, 2012; Andosch et al., 2012). In the present
      investigation we focus on amelioration of these adverse effects of cadmium,
      chromium and lead by supplying the cells with different antioxidants and
      essential micronutrients to obtain insight into metal uptake mechanisms and
      subcellular metal targets. This seems particularly interesting as Micrasterias is
      adapted to extremely low-concentrated, oligotrophic conditions in its natural bog
      environment. The divalent ions of iron, zinc and calcium were able to diminish
      the effects of the metals cadmium, chromium and lead on Micrasterias. Iron showed
      most ameliorating effects on cadmium and chromium in short- and long-term
      treatments and improved cell morphogenesis, ultrastructure, cell division rates
      and photosynthesis. Analytical transmission electron microscopic (TEM) methods
      (electron energy loss spectroscopy (EELS) and electron spectroscopic imaging
      (ESI)) revealed that chromium uptake was decreased when Micrasterias cells were
      pre-treated with iron, which resulted in no longer detectable intracellular
      chromium accumulations. Zinc rescued the detrimental effects of chromium on net
      photosynthesis, respiration rates and electron transport in PS II. Calcium and
      gadolinium were able to almost completely compensate the inhibiting effects of
      lead and cadmium on cell morphogenesis after mitosis, respectively. These results
      indicate that cadmium is taken up by calcium and iron transporters, whereas
      chromium appears to enter the algae cells via iron and zinc carriers. It was
      shown that lead is not taken up into Micrasterias at all but exerts its adverse
      effects on cell growth by substituting cell wall bound calcium. The antioxidants
      salicylic acid, ascorbic acid and glutathione were not able to ameliorate any of
      the investigated metal effects on the green alga Micrasterias when added to the
      culture medium. 

PMID- 24331432
TI  - Ectomycorrhizal Pisolithus albus inoculation of Acacia spirorbis and Eucalyptus
      globulus grown in ultramafic topsoil enhances plant growth and mineral nutrition
      while limits metal uptake.
AB  - Ectomycorrhizal fungi (ECM) isolates of Pisolithus albus (Cooke and Massee) from
      nickel-rich ultramafic topsoils in New Caledonia were inoculated onto Acacia
      spirorbis Labill. (an endemic Fabaceae) and Eucalyptus globulus Labill. (used as
      a Myrtaceae plant host model). The aim of the study was to analyze the growth of
      symbiotic ECM plants growing on the ultramafic substrate that is characterized by
      high and toxic metal concentrations i.e. Co, Cr, Fe, Mn and Ni, deficient
      concentrations of plant essential nutrients such as N, P, K, and that presents an
      unbalanced Ca/Mg ratio (1/19). ECM inoculation was successful with a plant level
      of root mycorrhization up to 6.7%. ECM symbiosis enhanced plant growth as
      indicated by significant increases in shoot and root biomass. Presence of ECM
      enhanced uptake of major elements that are deficient in ultramafic substrates; in
      particular P, K and Ca. On the contrary, the ECM symbioses strongly reduced
      transfer to plants of element in excess in soils; in particular all metals. ECM
      inoculated plants released metal complexing molecules as free thiols and oxalic
      acid mostly at lower concentrations than in controls. Data showed that ECM
      symbiosis helped plant growth by supplying uptake of deficient elements while
      acting as a protective barrier to toxic metals, in particular for plants growing
      on ultramafic substrate with extreme soil conditions. Isolation of indigenous and
      stress-adapted beneficial ECM fungi could serve as a potential tool for
      inoculation of ECM endemic plants for the successful restoration of ultramafic
      ecosystems degraded by mining activities. 

PMID- 24331433
TI  - Heat shock protein 70 is required for tabtoxinine-beta-lactam-induced cell death
      in Nicotiana benthamiana.
AB  - Tabtoxinine-beta-lactam (TbetaL), a non-specific bacterial toxin, is produced by
      Pseudomonas syringae pv. tabaci, the causal agent of tobacco wildfire disease.
      TbetaL causes death of plant cells through the inhibition of glutamine
      synthetase, which leads to an abnormal accumulation of ammonium ions and the
      characteristic necrotic wildfire lesions. To better understand the mechanisms
      involved in TbetaL-induced cell death, we studied its regulation in Nicotiana
      benthamiana. TbetaL-induced lesions, similar to those in controls, could be
      observed in SGT1-, RAR1- and Hsp90-silenced plants. In contrast, Hsp70-silenced
      plants showed suppression of lesion formation. Expression of hin1, a marker gene
      for the hypersensitive response (HR), which is a characteristic of programmed
      cell death in plants, was strongly induced in controls by TbetaL treatment but
      only slightly in Hsp70-silenced plants. However, in these TbetaL-treated Hsp70
      silenced plants, the amount of ammonium ions was considerably increased.
      Furthermore, the silencing of Hsp70 also suppressed l-methionine sulfoximine
      induced cell death and hin1 expression and caused the over-accumulation of
      ammonium ions. When inoculated directly with P. syringae pv. tabaci, Hsp70
      silenced plants showed only reduced symptoms. Our results suggest that the TbetaL
      induced pathway to cell death in N. benthamiana is at least partially similar to
      HR response, and that Hsp70 might play an essential role in these events. 

PMID- 24331434
TI  - Combating photooxidative stress in green hairy roots of Daucus carota cultivated
      under light irradiation.
AB  - The light-dependent generation of active oxygen species, which can disrupt normal
      metabolic process of plant, is termed as photo-oxidative stress. Plants are
      equipped with enzymatic and non-enzymatic antioxidative defence system to reduce
      the effect of such stress. Hairy root culture of Daucus carota when cultivated
      under continuous illumination (250 MUmol m(-2)s(-1)) turned green. To know the
      reason behind that and photo-oxidative stress response in green hairy roots,
      activities of several antioxidant enzymes were measured. When compared with
      normal hairy roots, green hairy roots showed an enhanced superoxide dismutase
      (SOD) activity. Treatment with a SOD inhibitor diethyldithiocarbamate led to
      suppression of SOD activity in a concentration-dependent manner in green hairy
      roots. Interestingly, SOD-suppressed root showed three-fold enhanced caffeic acid
      glucoside accumulation in the soluble fraction as compared to untreated ones.
      While ascorbate peroxidase activity showed marginal increase in green hairy
      roots, a decrease in the activities of guaiacol peroxidase and catalase were
      observed. SDS-PAGE of crude protein profile from green hairy roots showed a
      distinct band, which was absent in normal hairy roots. MALDI-TOF-MS/MS analysis
      of the extracted protein confirmed it as the large subunit of RuBisCO. RT-PCR
      based expression analysis of betaine aldehyde dehydrogenase showed enhanced
      transcript levels in green hairy roots as compared to normal hairy roots, whereas
      reverse trends were observed with the transcripts accumulation for phenylalanine
      ammonia-lyase and chalcone synthase. These findings corroborate with the in vitro
      BADH activities in hairy roots, and thus indicate an important role of this
      stress enzyme in combating photo-oxidative stress in green hairy roots upon
      continuous light exposure.

PMID- 24331436
TI  - Foreword.

PMID- 24331435
TI  - The emergence of mecC methicillin-resistant Staphylococcus aureus.
AB  - The report of methicillin-resistant Staphylococcus aureus (MRSA) encoding a
      divergent mecA gene in 2011 was highly significant. This homologue, designated
      mecC, poses diagnostic problems with the potential to be misdiagnosed as
      methicillin-sensitive S. aureus, with important potential consequences for
      individual patients and for the surveillance of MRSA. mecC MRSA have now been
      reported from 13 European countries and have been isolated from 14 different host
      species, with evidence of a recent increase in Denmark. The emergence of mecC
      MRSA is a topic of interest to human and veterinary microbiology, and we consider
      it timely to review here its discovery and subsequent investigation. 

PMID- 24331437
TI  - Transcatheter aortic valve-in-valve implantation for patients with degenerative
      surgical bioprosthetic valves.
AB  - Most surgical heart valves currently implanted are bioprosthetic tissue valves.
      Such valves deteriorate with time, eventually presenting with either stenosis or
      regurgitation. Reoperation, the current standard of care for failed valves,
      carries significant risk in terms of both morbidity and mortality. Implantation
      of a transcatheter valve inside a failed surgical valve (valve-in-valve
      procedure) has recently emerged as an alternative, less-invasive option. Although
      the procedure is similar in some aspects to transcatheter aortic valve
      implantation in the setting of native aortic valve stenosis, there are many
      differences that deserve special consideration. We review the potential and
      challenges of valve-in-valve implantation in patients with failing surgical
      aortic bioprostheses. 

PMID- 24331438
TI  - The key role of adherence for the effectiveness of antiretroviral-based
      prevention: state of the science and implications for the Asia-Pacific region.
AB  - Remarkable advances have been made in the last few years in biomedical strategies
      to prevent onward transmission of HIV (treatment as prevention (TasP)) and
      prevent infection among at-risk populations through pre-exposure prophylaxis
      (PrEP). Numerous issues remain heavily debated, primarily concerning the
      feasibility of leveraging resources for both widespread access to antiretroviral
      therapy (ART) for those living with HIV and access to effective prevention
      antiretrovirals (ARVs) among those at risk for infection. Even with consistent
      and wide-spread access to ARVs, the behavioural pathway from ARV access to
      successful rapid and durable suppression or reaching levels of PrEP adherence
      that confer high rates of protection is increasingly well recognised. For either
      'biobehavioural' strategy to have maximal individual and community benefit,
      individuals accessing them must actually use them. In this review, the unique and
      overlapping factors influencing adherence to ART and PrEP are identified, with an
      emphasis on the behavioural, social and structural facilitators and barriers to
      TasP and PrEP success. The implications of the current research base and evidence
      generated specifically within the Asia-Pacific region are discussed. 

PMID- 24331440
TI  - Dying in the twenty-first century.

PMID- 24331439
TI  - Imatinib treatment and Abeta42 in humans.
AB  - BACKGROUND: The first-line treatment in chronic myeloid leukemia (CML), imatinib,
      has been shown to decrease the production of amyloid-beta (Abeta) in vitro and in
      animal studies. However, whether imatinib has this effect in humans is not known.
      METHODS: Plasma levels of Abeta42 were analyzed in sequential samples from CML
      patients treated with imatinib (n=51). The effect of imatinib on Abeta production
      was also investigated in human embryonic kidney 293 (HEK293) cells overexpressing
      the amyloid precursor protein (APP) with the Swedish mutation, in mouse primary
      cortical neurons and in human Down syndrome embryonic stem-cell-derived cortical
      neurons. RESULTS: Twelve months of imatinib treatment did not lower plasma
      Abeta42 levels in CML patients, and imatinib treatment did not lead to less
      Abeta42 production in any of the in vitro models whereas beta- and gamma
      secretase inhibitors did. CONCLUSION: These data question the previously
      described role of imatinib in inhibiting amyloidogenic APP processing and as a
      drug candidate for AD.

PMID- 24331441
TI  - Integrating palliative care with disease-modifying therapy.

PMID- 24331442
TI  - When physicians and surrogates disagree about futility.

PMID- 24331443
TI  - Medical students and dying patients.

PMID- 24331444
TI  - The flipped classroom paradigm for teaching palliative care skills.

PMID- 24331445
TI  - Physician characteristics influence referral to end-of-life care.

PMID- 24331446
TI  - Serious illness communications checklist.

PMID- 24331447
TI  - The appropriate use of increasingly sophisticated life-sustaining technology.

PMID- 24331448
TI  - Legal constraints on pursuit of a "good death".

PMID- 24331449
TI  - Legislative attempts to improve end-of-life care in New York State.

PMID- 24331450
TI  - Whole-person, whole-community care at the end of life.

PMID- 24331451
TI  - Treatment of terminally ill patients according to Jewish law.

PMID- 24331452
TI  - When medicine is powerless.

PMID- 24331453
TI  - Impact of more restrictive blood transfusion strategies on clinical outcomes: a
      meta-analysis and systematic review.
AB  - BACKGROUND: There is accumulating evidence that restricting blood transfusions
      improves outcomes, with newer trials showing greater benefit from more
      restrictive strategies. We systematically evaluated the impact of various
      transfusion triggers on clinical outcomes. METHODS: The MEDLINE database was
      searched from 1966 to April 2013 to find randomized trials evaluating a
      restrictive hemoglobin transfusion trigger of <7 g/dL, compared with a more
      liberal trigger. Two investigators independently extracted data from the trials.
      Outcomes evaluated included mortality, acute coronary syndrome, pulmonary edema,
      infections, rebleeding, number of patients transfused, and units of blood
      transfused per patient. Extracted data also included information on study
      setting, design, participant characteristics, and risk for bias of the included
      trials. A secondary analysis evaluated trials using less restrictive transfusion
      triggers, and a systematic review of observational studies evaluated more
      restrictive triggers. RESULTS: In the primary analysis, pooled results from 3
      trials with 2364 participants showed that a restrictive hemoglobin transfusion
      trigger of <7 g/dL resulted in reduced in-hospital mortality (risk ratio [RR],
      0.74; confidence interval [CI], 0.60-0.92), total mortality (RR, 0.80; CI, 0.65
      0.98), rebleeding (RR, 0.64; CI, 0.45-0.90), acute coronary syndrome (RR, 0.44;
      CI, 0.22-0.89), pulmonary edema (RR, 0.48; CI, 0.33-0.72), and bacterial
      infections (RR, 0.86; CI, 0.73-1.00), compared with a more liberal strategy. The
      number needed to treat with a restrictive strategy to prevent 1 death was 33.
      Pooled data from randomized trials with less restrictive transfusion strategies
      showed no significant effect on outcomes. CONCLUSIONS: In patients with critical
      illness or bleed, restricting blood transfusions by using a hemoglobin trigger of
      <7 g/dL significantly reduces cardiac events, rebleeding, bacterial infections,
      and total mortality. A less restrictive transfusion strategy was not effective.

PMID- 24331454
TI  - Effect of nitric oxide on the cyclic guanosine monophosphate (cGMP) pathway
      during meiosis resumption in bovine oocytes.
AB  - Nitric oxide (NO) is a chemical messenger involved in the control of oocyte
      maturation. It stimulates guanylate cyclase to produce cyclic guanosine
      monophosphate (cGMP), which in turn activates cGMP-dependent protein kinase (PKG)
      and some phosphodiesterases that may interfere with cAMP levels, a nucleotide
      also involved in meiosis resumption. The aim of this study was to determine the
      role played by NO on the cGMP/cAMP pathway during meiosis resumption in bovine
      oocytes. The effects of increasing NO generated by S-nitroso-N
      acetylpenicillamine (SNAP; 10(-7)-10(-3) mol/L) and of other drugs that may
      affect the NO/cGMP pathway (proptoporfirin IX and 8-Br-cGMP) on meiosis
      resumption were investigated in bovine cumulus-oocyte complexes (COCs) matured
      for 9 hours in a semidefined medium (TCM199 + 3 mg/mL BSA). The COCs matured with
      10(-7) mol/L SNAP associated or not with 100 MUmol/L oxadiazole-one quinoxaline,
      a guanylate cyclase inhibitor, also had their cGMP and cAMP levels measured
      during the first hours of maturation (1, 3, and 6 hours). Quantitative polymerase
      chain reaction was performed by real-time polymerase chain reaction to determine
      the effects of NO on expression of genes encoding for enzymes of the NO/guanylate
      cyclase/cGMP and cAMP pathways during the first 9 hours of oocyte maturation.
      Increasing NO levels using 10(-7) mol/L SNAP resulted in lower rate of germinal
      vesicle breakdown (36% germinal vesicle breakdown; P < 0.05) at 9 hours IVM,
      whereas control group and the treatments with 10(-9) and 10(-8) mol/L SNAP showed
      about 70% germinal vesicle breakdown (P > 0.05). A temporary increase in cGMP
      levels was also observed with the same treatment (4.51 pmol/COC) at 1 hour IVM,
      which was superior to the control group (2.97 pmol/COC; P < 0.05) and was
      reversed by inhibiting guanylate cyclase activity with 100 MUmol/L oxadiazole-one
      quinoxaline. Neither cAMP levels nor gene expression were affected by NO. These
      results suggest that NO acts via guanylate cyclase/cGMP and that even a temporary
      increase in cGMP levels leads to a delay in meiosis resumption, even when cAMP
      levels have declined. Nitric oxide does not act on oocyte maturation by affecting
      cAMP levels or the expression of genes related to the NO/guanylate cyclase/cGMP
      and cAMP pathways. Also, to our knowledge this is the first report to detect
      PKG1, PKG2, phosphodiesterase-5A, ADCY3, ADCY6, and ADCY9 transcripts in bovine
      oocytes. 

PMID- 24331456
TI  - Working memory span in mild cognitive impairment. Influence of processing speed
      and cognitive reserve.
AB  - BACKGROUND: Mild cognitive impairment (MCI) often includes episodic memory
      impairment, but can also involve other types of cognitive decline. Although
      previous studies have shown poorer performance of MCI patients in working memory
      (WM) span tasks, different MCI subgroups were not studied. METHODS: In the
      present exploratory study, 145 participants underwent extensive cognitive
      evaluation, which included three different WM span tasks, and were classified
      into the following groups: multiple-domain amnestic MCI (mda-MCI), single-domain
      amnestic MCI (sda-MCI), and controls. General linear model was conducted by
      considering the WM span tasks as the within-subject factor; the group (mda-MCI,
      sda-MCI, and controls) as the inter-subject factor; and processing speed,
      vocabulary and age as covariates. Multiple linear regression models were also
      used to test the influence of processing speed, vocabulary, and other cognitive
      reserve (CR) proxies. RESULTS: Results indicate different levels of impairment of
      WM, with more severe impairment in mda-MCI patients. The differences were still
      present when processing resources and CR were controlled. CONCLUSIONS: Between
      group differences can be understood as a manifestation of the greater severity
      and widespread memory impairment in mda-MCI patients and may contribute to a
      better understanding of continuum from normal controls to mda-MCI patients.
      Processing speed and CR have a limited influence on WM scores, reducing but not
      removing differences between groups.

PMID- 24331455
TI  - Interaction of the neuropeptide S receptor gene Asn107Ile variant and
      environment: contribution to affective and anxiety disorders, and suicidal
      behaviour.
AB  - Neuropeptide S is involved in anxiety and arousal modulation, and the functional
      polymorphism Asn107Ile (rs324981, A > T) of the neuropeptide S receptor gene
      (NPSR1) is associated with panic disorder and anxiety/fear-related traits. NPSR1
      also interacts with the environment in shaping personality and impulsivity. We
      therefore examined whether the NPSR1 A/T polymorphism is associated with
      affective and anxiety disorders in a population-representative sample. Lifetime
      psychiatric disorders were assessed by MINI interview (n = 501) in the older
      cohort of the longitudinal Estonian Children Personality, Behaviour and Health
      Study (ECPBHS). Anxiety (STAI), self-esteem (RSES), depression (MADRS), suicide
      attempts and environmental factors were self-reported in both the younger
      (original n = 583) and the older cohort (original n = 593). Most of the NPSR1
      effects were sex-specific and depended on environmental factors. Females with the
      functionally least active NPSR1 AA genotype and exposed to environmental
      adversity had affective/anxiety disorders more frequently; they also exhibited
      higher anxiety and depressiveness, and lower self-esteem. Female AA homozygotes
      also reported suicidal behaviour more frequently, and this was further
      accentuated by adverse family environment. In the general population, the NPSR1
      A/T polymorphism together with environmental factors is associated with anxious,
      depressive and activity-related traits, increased prevalence of affective/anxiety
      disorders and a higher likelihood of suicidal behaviour. 

PMID- 24331457
TI  - A hydrogen boost for salmonella.
AB  - Although the microbiota protects the host from infection, pathogens are still
      able to colonize and cause disease. In this issue of Cell Host & Microbe, Maier
      et al. (2013) provide mechanistic insight into the initial stages of Salmonella
      growth in the gut, showing that microbiota-derived hydrogen provides an energy
      boost to Salmonella. 

PMID- 24331458
TI  - Streptococcus pyogenes escapes from autophagy.
AB  - Autophagy is important for innate defense against intracellular bacteria, such as
      Group A Streptococcus (GAS). In this issue of Cell Host & Microbe, Barnett et al.
      (2013) demonstrate that the globally disseminated serotype M1T1 clone of GAS can
      evade autophagy via streptococcal cysteine protease SpeB-mediated degradation of
      ubiquitin-LC3 adaptor proteins. 

PMID- 24331459
TI  - Epstein-Barr viral productive amplification reprograms nuclear architecture, DNA
      replication, and histone deposition.
AB  - The spontaneous transition of Epstein-Barr virus (EBV) from latency to productive
      infection is infrequent, making its analysis in the resulting mixed cell
      populations difficult. We engineered cells to support this transition efficiently
      and developed EBV DNA variants that could be visualized and measured as
      fluorescent signals over multiple cell cycles. This approach revealed that EBV's
      productive replication began synchronously for viral DNAs within a cell but
      asynchronously between cells. EBV DNA amplification was delayed until early S
      phase and occurred in factories characterized by the absence of cellular DNA and
      histones, by a sequential redistribution of PCNA, and by localization away from
      the nuclear periphery. The earliest amplified DNAs lacked histones accompanying a
      decline in four histone chaperones. Thus, EBV transits from being dependent on
      the cellular replication machinery during latency to commandeering both that
      machinery and nuclear structure for its own reproductive needs. 

PMID- 24331460
TI  - Structural basis for signaling by exclusive EDS1 heteromeric complexes with
      SAG101 or PAD4 in plant innate immunity.
AB  - Biotrophic plant pathogens encounter a postinfection basal resistance layer
      controlled by the lipase-like protein enhanced disease susceptibility 1 (EDS1)
      and its sequence-related interaction partners, senescence-associated gene 101
      (SAG101) and phytoalexin deficient 4 (PAD4). Maintainance of separate EDS1 family
      member clades through angiosperm evolution suggests distinct functional
      attributes. We report the Arabidopsis EDS1-SAG101 heterodimer crystal structure
      with juxtaposed N-terminal alpha/beta hydrolase and C-terminal alpha-helical EP
      domains aligned via a large conserved interface. Mutational analysis of the EDS1
      SAG101 heterodimer and a derived EDS1-PAD4 structural model shows that EDS1
      signals within mutually exclusive heterocomplexes. Although there is evolutionary
      conservation of alpha/beta hydrolase topology in all three proteins, a
      noncatalytic resistance mechanism is indicated. Instead, the respective N
      terminal domains appear to facilitate binding of the essential EP domains to
      create novel interaction surfaces on the heterodimer. Transitions between
      distinct functional EDS1 heterodimers might explain the central importance and
      versatility of this regulatory node in plant immunity. 

PMID- 24331461
TI  - Nasal microenvironments and interspecific interactions influence nasal microbiota
      complexity and S. aureus carriage.
AB  - The indigenous microbiota of the nasal cavity plays important roles in human
      health and disease. Patterns of spatial variation in microbiota composition may
      help explain Staphylococcus aureus colonization and reveal interspecies and
      species-host interactions. To assess the biogeography of the nasal microbiota, we
      sampled healthy subjects, representing both S. aureus carriers and noncarriers at
      three nasal sites (anterior naris, middle meatus, and sphenoethmoidal recess).
      Phylogenetic compositional and sparse linear discriminant analyses revealed
      communities that differed according to site epithelium type and S. aureus culture
      based carriage status. Corynebacterium accolens and C. pseudodiphtheriticum were
      identified as the most important microbial community determinants of S. aureus
      carriage, and competitive interactions were only evident at sites with ciliated
      pseudostratified columnar epithelium. In vitro cocultivation experiments provided
      supporting evidence of interactions among these species. These results highlight
      spatial variation in nasal microbial communities and differences in community
      composition between S. aureus carriers and noncarriers. 

PMID- 24331462
TI  - Microbiota-derived hydrogen fuels Salmonella typhimurium invasion of the gut
      ecosystem.
AB  - The intestinal microbiota features intricate metabolic interactions involving the
      breakdown and reuse of host- and diet-derived nutrients. The competition for
      these resources can limit pathogen growth. Nevertheless, some enteropathogenic
      bacteria can invade this niche through mechanisms that remain largely unclear.
      Using a mouse model for Salmonella diarrhea and a transposon mutant screen, we
      discovered that initial growth of Salmonella Typhimurium (S. Tm) in the
      unperturbed gut is powered by S. Tm hyb hydrogenase, which facilitates
      consumption of hydrogen (H2), a central intermediate of microbiota metabolism. In
      competitive infection experiments, a hyb mutant exhibited reduced growth early in
      infection compared to wild-type S. Tm, but these differences were lost upon
      antibiotic-mediated disruption of the host microbiota. Additionally, introducing
      H2-consuming bacteria into the microbiota interfered with hyb-dependent S. Tm
      growth. Thus, H2 is an Achilles' heel of microbiota metabolism that can be
      subverted by pathogens and might offer opportunities to prevent infection. 

PMID- 24331463
TI  - Tn-Seq analysis of Vibrio cholerae intestinal colonization reveals a role for
      T6SS-mediated antibacterial activity in the host.
AB  - Analysis of genes required for host infection will provide clues to the drivers
      of evolutionary fitness of pathogens like Vibrio cholerae, a mounting threat to
      global heath. We used transposon insertion site sequencing (Tn-seq) to
      comprehensively assess the contribution of nearly all V. cholerae genes toward
      growth in the infant rabbit intestine. Four hundred genes were identified as
      critical to V. cholerae in vivo fitness. These included most known colonization
      factors and several new genes affecting the bacterium's metabolic properties,
      resistance to bile, and ability to synthesize cyclic AMP-GMP. Notably, a mutant
      carrying an insertion in tsiV3, encoding immunity to a bacteriocidal type VI
      secretion system (T6SS) effector VgrG3, exhibited a colonization defect. The
      reduced in vivo fitness of tsiV3 mutants depends on their cocolonization with
      bacterial cells carrying an intact T6SS locus and VgrG3 gene, suggesting that the
      V. cholerae T6SS is functional and mediates antagonistic interbacterial
      interactions during infection.

PMID- 24331464
TI  - Natural killer cell-mediated host defense against uropathogenic E. coli is
      counteracted by bacterial hemolysinA-dependent killing of NK cells.
AB  - Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract
      infections (UTIs) in humans. While the importance of natural killer (NK) cells in
      innate immune protection against tumors and viral infections is well documented,
      their role in defense against bacterial infections is still emerging, and their
      involvement in UPEC-mediated UTI is practically unknown. Using a systematic
      mutagenesis approach, we found that UPEC adheres to NK cells primarily via its
      type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence
      of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine
      TNF-alpha, which results in decreased bacterial numbers in vitro and reduction of
      bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF
      alpha production, which UPEC counteracts by hemolysinA-mediated killing of NK
      cells, representing a previously unrecognized host defense and microbial
      counterattack mechanism in the context of UTI.

PMID- 24331465
TI  - The globally disseminated M1T1 clone of group A Streptococcus evades autophagy
      for intracellular replication.
AB  - Autophagy is reported to be an important innate immune defense against the
      intracellular bacterial pathogen Group A Streptococcus (GAS). However, the GAS
      strains examined to date belong to serotypes infrequently associated with human
      disease. We find that the globally disseminated serotype M1T1 clone of GAS can
      evade autophagy and replicate efficiently in the cytosol of infected cells.
      Cytosolic M1T1 GAS (strain 5448), but not M6 GAS (strain JRS4), avoids
      ubiquitylation and recognition by the host autophagy marker LC3 and ubiquitin-LC3
      adaptor proteins NDP52, p62, and NBR1. Expression of SpeB, a streptococcal
      cysteine protease, is critical for this process, as an isogenic M1T1 DeltaspeB
      mutant is targeted to autophagy and attenuated for intracellular replication.
      SpeB degrades p62, NDP52, and NBR1 in vitro and within the host cell cytosol.
      These results uncover a proteolytic mechanism utilized by GAS to escape the host
      autophagy pathway that may underpin the success of the M1T1 clone.

PMID- 24331466
TI  - An infection-relevant transcriptomic compendium for Salmonella enterica Serovar
      Typhimurium.
AB  - Bacterial transcriptional networks consist of hundreds of transcription factors
      and thousands of promoters. However, the true complexity of transcription in a
      bacterial pathogen and the effect of the environments encountered during
      infection remain to be established. We present a simplified approach for global
      promoter identification in bacteria using RNA-seq-based transcriptomic analyses
      of 22 distinct infection-relevant environmental conditions. Individual RNA
      samples were combined to identify most of the 3,838 Salmonella enterica serovar
      Typhimurium promoters in just two RNA-seq runs. Individual in vitro conditions
      stimulated characteristic transcriptional signatures, and the suite of 22
      conditions induced transcription of 86% of all S. Typhimurium genes. We highlight
      the environmental conditions that induce the Salmonella pathogenicity islands and
      present a small RNA expression landscape of 280 sRNAs. This publicly available
      compendium of environmentally controlled expression of every transcriptional
      feature of S. Typhimurium constitutes a useful resource for the bacterial
      research community.

PMID- 24331468
TI  - A study of the metabolism of transplanted tumor in the lung by micro PET/CT in
      mice.
AB  - The difference of tumor metabolism from that of normal tissue is an important
      factor for diagnosis through functional imaging such as positron emission
      tomography (PET). A quantitative description of the metabolic process will help
      to improve the diagnosis methods. In this study, the metabolism of tumor in lung
      was quantitatively described in mice. The melanoma was transplanted into the lung
      of mice, and the metabolism of the transplanted tumor was detected by micro
      PET/CT with [(18)F]fluoro-2-deoxy-D-glucose (FDG). Nine mice were transplanted
      with B16 melanoma cells through their tail vein. Lung tumor was detected by
      pathological method. The lesions smaller than 1mm could hardly be directly
      detected directly by micro PET/CT, while the tumor with a 1-4mm diameter could be
      detected by micro PET/CT. A metabolic model with three compartments was
      separately established for lung tumors and normal lung tissues. In this model,
      the lung cancer had a significantly higher metabolic rate constant as compared to
      that of the normal lung tissue (p=0.01). The outputs of the model fit well with
      the original curve from the dynamic images. It is also found that difference of
      tissue activity between tumors and normal lung tissues varied along scan time.
      Through this comparison, it was suggested that the difference in metabolism
      between the lung tissue and the tumor might contribute to the tumor diagnosis.

PMID- 24331469
TI  - Re: carbonic anhydrase IX (CAIX) is not an independent predictor of outcome in
      patients with clear cell renal cell carcinoma (ccRCC) after long-term follow-up.

PMID- 24331467
TI  - Genome-wide mapping of DNA methylation in the human malaria parasite Plasmodium
      falciparum.
AB  - Cytosine DNA methylation is an epigenetic mark in most eukaryotic cells that
      regulates numerous processes, including gene expression and stress responses. We
      performed a genome-wide analysis of DNA methylation in the human malaria parasite
      Plasmodium falciparum. We mapped the positions of methylated cytosines and
      identified a single functional DNA methyltransferase (Plasmodium falciparum DNA
      methyltransferase; PfDNMT) that may mediate these genomic modifications. These
      analyses revealed that the malaria genome is asymmetrically methylated and shares
      common features with undifferentiated plant and mammalian cells. Notably, core
      promoters are hypomethylated, and transcript levels correlate with intraexonic
      methylation. Additionally, there are sharp methylation transitions at nucleosome
      and exon-intron boundaries. These data suggest that DNA methylation could
      regulate virulence gene expression and transcription elongation. Furthermore, the
      broad range of action of DNA methylation and the uniqueness of PfDNMT suggest
      that the methylation pathway is a potential target for antimalarial strategies. 

PMID- 24331471
TI  - Re: an investigation of risk factors for renal cell carcinoma by histologic
      subtype in two case-control studies.

PMID- 24331477
TI  - Re: benign prostatic hyperplasia is a significant risk factor for bladder cancer
      in diabetic patients: a population-based cohort study using the national health
      insurance in Taiwan.

PMID- 24331479
TI  - Re: effect of soy protein isolate supplementation on biochemical recurrence of
      prostate cancer after radical prostatectomy: a randomized trial.

PMID- 24331480
TI  - Re: consumption of fish products across the lifespan and prostate cancer risk.

PMID- 24331481
TI  - Re: urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a
      baseline analysis in the canary prostate active surveillance study.

PMID- 24331490
TI  - Re: finding unrecognized information in overactive bladder clinical trial data: a
      new approach to understanding placebo and treatment effects.

PMID- 24331493
TI  - Re: predictors of successful first-line antimuscarinic monotherapy in men with
      enlarged prostate and predominant storage symptoms.

PMID- 24331494
TI  - Re: intravesical prostatic protrusion can be a predicting factor for the
      treatment outcome in patients with lower urinary tract symptoms due to benign
      prostatic obstruction treated with tamsulosin.

PMID- 24331496
TI  - Re: prospective study of restless legs syndrome and risk of erectile dysfunction.

PMID- 24331499
TI  - Re: the effect of combined antihypertensive treatment (felodipine with either
      irbesartan or metoprolol) on erectile function: a randomized controlled trial.

PMID- 24331506
TI  - Re: ovarian torsion: diagnosis of inclusion mandates earlier intervention.

PMID- 24331512
TI  - Re: CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and
      improves the efficacy of radiotherapy in prostate cancer.

PMID- 24331516
TI  - Feasibility of utilising an infrared-thermographic technique for early detection
      of subclinical mastitis in dairy camels (Camelus dromedarius).
AB  - Despite the proven ability of infrared thermography (IRT) technology for early
      detection of subclinical mastitis in dairy cows/sheep/goats, studies on its
      diagnostic feasibility in dairy camels are lacking. Sixty-five lactating camels
      in mid lactation, machine milked twice-daily and managed under intensive
      conditions were screened to evaluate the feasibility of utilising IRT compared
      with other routine indicators in detecting subclinical mastitis. Immediately
      before the morning milking, a portable infrared camera was used to obtain
      thermograms in duplicate for the front and rear left quarters to determine the
      udder surface temperature (UST). Thereafter, milk samples from quarters were
      collected, and processed for California mastitis test (CMT) score and somatic
      cell count (SCC). In the present study, CMT score was used to define subclinical
      mastitis and the feasibility of IRT to detect subclinical mastitis was compared
      with CMT and SCC. According to CMT score, subclinical mastitic udders had an
      average UST of 1.42  degrees C greater (P<0.0001) than healthy udders. The
      relationship between UST and CMT was found to be highly correlated (r=0.77;
      P<0.001), and UST was linearly increased as the CMT increased [UST ( degrees
      C)=34.86+0.66*CMT score; R 2=0.65; P<0.001]. Additionally, high correlations were
      obtained between UST and SCC score (r=0.75; P<0.001) and the relationship between
      UST and SCC was fitted best to a logarithmic equation [UST,  degrees
      C=33.39+0.88*Log (SCC, *103 cells/ml), R 2=0.61, P<0.001]. The cut-off value,
      sensitivity, specificity and area under the receiver operating characteristics
      (ROC) curve for UST were 35.15  degrees C, 0.90, 0.98, and 0.95, respectively,
      when subclinical mastitis was defined according to CMT score, and were 35.70 
      degrees C, 0.89, 0.96 and 0.94, respectively, when categorised according to the
      obtained SCC threshold (SCC=432 000 cells/ml). In conclusion, IRT, as an indirect
      non-invasive screening method, was highly feasible for distinguishing subclinical
      mastitic udders in dairy camels, which is crucial to treat mastitis early and
      efficiently. 

PMID- 24331517
TI  - Coping with causal uncertainty through alcohol use.
AB  - OBJECTIVE: We examined whether individuals use alcohol in order to cope with
      causal uncertainty (i.e., doubt about the causes of events). We predicted that
      higher levels of causal uncertainty would be associated with stronger coping
      motives, which, in turn, would predict more problems with alcohol. We also
      examined age as a moderator, with the expectation that stronger associations
      would be found among younger adults. METHOD: Two hundred sixty-three adults who
      drank alcohol at least occasionally completed questionnaires assessing causal
      uncertainty, correlates of causal uncertainty, motives for drinking, alcohol
      consumption, and alcohol-related problems. RESULTS: Moderated mediation analyses
      revealed that among younger adults, causal uncertainty had a significant indirect
      effect on problems with alcohol through coping with depression and enhancement
      motives. Among older adults, there were no significant associations between
      causal uncertainty and alcohol motives or problems. The effect via the coping
      with depression motive held even after controlling for alcohol consumption and
      the major cognitive and affective correlates of causal uncertainty, whereas the
      effect via the enhancement motive became nonsignificant. CONCLUSIONS: Our results
      are consistent with the idea that younger adults use alcohol to cope with causal
      uncertainty, putting them at greater risk for alcohol-related problems.

PMID- 24331519
TI  - Reducing obesity related chronic disease: Global policy development and actions
      from New Zealand.

PMID- 24331518
TI  - Obesity and increased risk of type 2 diabetes mellitus: The aetiological role of
      depression.

PMID- 24331520
TI  - A perspective on obesity cardiomyopathy.
AB  - SUMMARY: Obesity is a major health concern worldwide as obese individuals have a
      greater risk of death from any cause than normal-weight individuals. As the
      number of overweight children and adolescents continues to rise, so too has the
      scope of the obesity epidemic grown substantially. In this article, the authors
      discuss the role of obesity in the development of heart failure and the
      pathophysiology of obesity cardiomyopathy, as well as explore the potential role
      of bariatric surgery and mechanical circulatory support devices (MCSD) as
      potential therapeutic targets.:

PMID- 24331521
TI  - Effect of bariatric surgery on left ventricular geometry and function in severe
      obesity.
AB  - SUMMARY:  OBJECTIVE: Weight loss improves cardiac abnormalities associated with
      severe obesity. We evaluated the impact of weight loss following laparoscopic
      gastric bypass (LGBP) on left ventricular (LV) geometry and function in obese
      patients. METHODS: Twenty-six patients with severe obesity (41 +/- 8 years, 50%
      women) underwent Doppler echocardiograms before and after LGBP, to measure LV
      geometry, excess of LV mass relative to hemodynamic load and systolic and
      diastolic function. RESULTS: Pre-operatively, 85% of patients exhibited LVH, and
      62% hypertension and metabolic syndrome, reflecting high cardiometabolic risk.
      After 8 +/- 4 months of follow-up, the average weight loss was 19 +/- 8%. Weight
      loss was significantly associated with improved metabolic parameters and reduced
      heart rate (-9 bpm), systolic (-11 mmHg) and diastolic (-6 mmHg) blood pressure
      (all p < 0.02). After surgery, there was significant reduction in relative wall
      thickness (0.43 +/- 0.07 versus 0.39 +/- 0.06), LV mass index (63 +/- 14 g/m(2.7)
      versus 49 +/- 10 g/m(2.7)) and excess of LV mass in relation to hemodynamic load
      (all p < 0.004). LVH remained in 54% of patients, hypertension in 23% and
      metabolic syndrome in 27%. Ejection fraction and Doppler indices of diastolic
      function did not change significantly, even after adjusting for changes in heart
      rate. All favorable changes in LV geometry and function were also confirmed in
      the subgroup with <9 month follow-up (median), whereas no further improvement
      could be detected in patients with longer follow-up. CONCLUSIONS: In patient with
      severe obesity, LV geometry and systolic function improved rapidly after LGBP,
      without evidence of further improvement during prolonged follow-up.

PMID- 24331522
TI  - Relationship between obesity, depression, and disability in middle-aged women.
AB  - SUMMARY:  BACKGROUND: Obesity and depression are closely linked, and each has
      been associated with disability. However, few studies have assessed inter
      relationships between these conditions. DESIGN AND METHODS: In this study, 4641
      women aged 40-65 completed a structured telephone interview including self
      reported height and weight, the Patient Health Questionnaire (PHQ) assessment of
      depression, and the World Health Organization Disability Assessment Schedule II
      (WHODAS II). The survey response rate was 62%. We used multivariable regression
      models to assess relationships between obesity, depression, and disability.
      RESULTS: The mean age was 52 years; 82% were White; and 80% were currently
      employed. One percent were underweight, 39% normal weight, 27% overweight, and
      34% obese. Mild depressive symptoms were present in 23% and moderate-to-severe
      symptoms were present in 13%. After multivariable adjustment, depression was a
      strong independent predictor of worse disability in all 7 domains (cognition,
      mobility, self-care, social interaction, role functioning, household, and work),
      but obesity was only a significant predictor of greater mobility, role
      functioning, household, and work limitations (P < 0.05) (overweight was not
      significantly associated with any disability domain). Overall, the effect on
      disability was stronger and more pervasive for depression than obesity, and there
      was no significant interaction between the two conditions (P > 0.05). Overweight
      and obesity were associated with 5760 days of absenteeism per 1000 person-years,
      and depression was associated with 18,240 days of absenteeism per 1000 person
      years. CONCLUSIONS: The strong relationships between depression, obesity and
      disability suggest that these conditions should be routinely screened and treated
      among middle-aged women.

PMID- 24331523
TI  - Obesity as an independent risk for left ventricular diastolic dysfunction in 692
      Japanese patients.
AB  - SUMMARY:  BACKGROUND: Both obesity and left ventricular (LV) diastolic
      dysfunction are associated with an increased risk of cardiovascular morbidity and
      mortality. There is a paucity of data as to whether obesity is independently
      associated with LV diastolic dysfunction. METHODS: Adult patients with sinus
      rhythm referred for a transthoracic echocardiography between July, 2007, and
      December, 2007, were prospectively included. Exclusion criteria were patient who
      had a history of congenital or valvular heart disease, treatment with pacemaker
      implantation or implantable cardioverter defibrillator, myocardial infarction, or
      impaired LV systolic function. Diastolic function was classified by an algorithm
      incorporating data from mitral and pulmonary venous flow indices, and Doppler
      tissue imaging. Body mass index (BMI) was evaluated as a categorical variable
      (normal weight <25.0 kg/m(2); overweight 25.0 to <30.0 kg/m(2); and obese >=30
      kg/m(2)). Logistic models were used to assess the risk of abnormal LV diastolic
      function associated with BMI categories. RESULTS: Of a total number of 692
      patients who met all study criteria (mean 59 +/- 15 year-old; 50% women, 48%
      hypertension, 16% diabetes, 26% overweight, 8% obese), 538 (78%) had abnormal LV
      diastolic function. In multivariate analyses adjusting for age, sex, and
      cardiovascular risk factors, obesity was independently associated with LV
      diastolic dysfunction (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.12
      7.88; P = 0.03) compared to normal weight. LV mass did not weaken this
      association (OR: 2.88, 95% CI: 1.08-7.68; P = 0.04). Overweight was not
      independently associated with LV diastolic dysfunction. CONCLUSION: Obesity was
      associated with LV diastolic dysfunction independent of cardiovascular risk
      factors and LV mass.

PMID- 24331524
TI  - LST8 level controls basal p70 S6 kinase and Akt phosphorylations, and mTORC1 and
      mTORC2 negatively regulate each other by competing for association with LST8.
AB  - SUMMARY: LST8 is a component of both mTOR complex 1 (mTORC1) and mTOR complex 2
      (mTORC2). Herein, to examine the role of LST8, a common component of mTOR
      complexes, in the regulation of mTORC1 and mTORC2, first, we showed over
      expression of LST8 in HepG2 to markedly enhance basal phosphorylation levels of
      not only p70 S6 kinase but also Akt. In contrast, LST8 knockdown by siRNA in
      HepG2 decreased phosphorylation levels of both p70 S6 kinase and Akt. These
      results indicate the LST8 expression level to determine basal mTORC1 and mTORC2
      activities, since LST8 appears to be the component present at the lowest level in
      both mTORC1 and mTORC2 complexes. Previously, we reported S6 kinase
      phosphorylation to be reduced by over-expression of the Cterminally deleted
      Raptor mutant (Raptor-DeltaCT) not binding to mTOR or LST8, while phosphorylation
      levels of Akt were markedly enhanced with no alteration in IRS-1 phosphorylation
      or PI 3-kinase activity. Using Raptor-DeltaCT, we investigated the competition
      for association with LST8 between mTORC1 and mTORC2. Over-expression of Raptor
      DeltaCT abolished formation of the Raptor, S6 kinase, mTOR and LST8 complex,
      while the amount of LST8 in the Rictor-mTOR complex was increased. Therefore, it
      is likely that Raptor-mTOR and Rictor-mTOR complexes compete for association with
      LST8, and this mechanism may contribute to the reciprocal negative regulations of
      mTORC1 and mTORC2 activities, in terms of their LST8 components.:

PMID- 24331525
TI  - Masked function of amino acid sensors on pancreatic hormone secretion in
      ventromedial hypothalamic (VMH) lesioned rats with marked hyperinsulinemia.
AB  - SUMMARY: In neural regulation of the endocrine pancreas, there is much evidence
      to suggest that vagal efferents alter insulin and glucagon secretion, but less
      information on the effects of vagal afferents. In this study, we investigated the
      role and function of afferent fibers of the vagus nerve in normal and
      ventromedial hypothalamic (VMH) lesioned rats with marked hyperinsulinemia. In
      normal rats, hepatic vagotomy was associated with intraperitoneal (ip) arginine
      induced enhancement of insulin and glucagon secretion without an accompanying
      change in blood glucose levels, ip leucine induced enhancement of insulin
      secretion accompanied by a decrease in blood glucose levels, and ip alanine
      induced enhancement of glucagon secretion accompanied by an increase in blood
      glucose levels. In VMH lesioned rats with marked hyperinsulinemia, none of these
      amino acids caused significant changes in insulin and glucagon secretion. We
      conclude that amino acid sensors in normal rats inhibit excess release of
      pancreatic hormones induced directly by intake of amino acids, such as that in
      excess protein ingestion, and maintain blood glucose levels within the normal
      range. In contrast, in VMH lesioned rats with marked hyperinsulinemia, the
      function of the amino acid sensors is masked due to the marked hyperinsulinemia
      in these rats.:

PMID- 24331526
TI  - Cell proliferation in ventromedial hypothalamic lesioned rats inhibits acute
      gastric mucosal lesions.
AB  - AIM: The role of mucosal layer thickness on prevention of acute gastric mucosal
      lesions (AGMLs) was examined in ventromedial hypothalamic (VMH)-lesioned rats.
      MATERIALS AND METHODS: The incidence of AGMLs after 48-h fasting and 60% ethanol
      injection into the stomach after 24-h fasting, aggressive factors (gastric acid
      and serum gastrin) and defensive factors [hexosamine, gastric mucosal blood flow
      (GMBF), serum thiobarbituric acid reacting substances (TBARS), and thickness of
      the gastric mucosal layer] were evaluated in VMH-lesioned rats. The effects of
      cell proliferation on the gastric mucosal layer of these rats were evaluated by H
      E staining and immunostaining with proliferating cell nuclear antigen (PCNA).
      RESULTS: After 48-h fasting, no AGMLs were observed in VMH-lesioned and sham VMH
      lesioned rats (controls). With 60% ethanol administration after 24-h fasting, the
      numbers of AGMLs were similar in the two groups, but the ulcer index, a marker of
      ulcer formation, was lower in VMH-lesioned rats compared to that in sham VMH
      lesioned rats. VMH-lesioned rats showed increased gastric acid secretion and
      serum gastrin compared to sham VMH-lesioned rats, indicating an increase in
      aggressive factors in VMH-lesioned rats. The two groups had similar levels of
      gastric mucosal hexosamine, GMBF, and gastric mucosal TBARS, but VMH-lesioned
      rats had an increased thickness of the mucosal cell layer, indicating an increase
      in defensive factors in these rats. Histologically, VMH-lesioned rats had an
      increased total mucosal cell layer, especially for the surface epithelial cell
      layer, and an increased PCNA-labeling index, a marker of cell proliferation,
      especially in the proliferative zones of gastric mucosa, indicating increased
      cell proliferation in the proliferative zone of the gastric mucosa. CONCLUSION:
      VMH-lesioned rats are resistant to AGML formation due to increased cell
      proliferation in gastric mucosa through elevating the levels of defensive factors
      over those of aggressive factors.

PMID- 24331527
TI  - Ventromedial hypothalamic lesions enhance small intestinal cell proliferation in
      mice.
AB  - SUMMARY:  BACKGROUND: We have found previously that ventromedial hypothalamic
      lesions (VMH) enhance cell proliferation in the visceral organs through vagal
      hyperactivity in rats. The goal of the current study was to determine the
      characteristics and nature of cell proliferation in the small intestine in VMH
      lesioned mice. METHODS: The weight and length of the small intestine, thickness
      of the mucosal and muscle layers, number of proliferating cell nuclear antigen
      (PCNA)-positive cells, and mitotic cell count in the mucosal layer in VMH
      lesioned and Sham VMH-lesioned mice were determined at 7 days after the
      operation. RESULTS: The weight and length of the small intestine in VMH-lesioned
      mice were significantly greater than those in Sham VMH-lesioned mice, by 11.6%
      and 15.0%, respectively. The thicknesses of the mucosal and muscle layers of the
      small intestine in VMH-lesioned mice were also significantly greater than those
      in Sham VMH-lesioned mice, by 12.7% and 12.5%, respectively. PCNA-positive cells
      and mitotic cells in the mucosal layer were densely present in crypts in VMH
      lesioned mice, and were significantly increased by 31.9% and 71.7%, respectively,
      compared to Sham VMH-lesioned mice. CONCLUSIONS: These results demonstrate that
      VMH lesions in mice enhance cell proliferation in the mucosal layers and cause
      cell hypertrophy or cell proliferation in the muscle layers of the small
      intestine, which increases the weight and length of the small intestine. VMH
      lesions in mice may be a new tool for identifying growth factors and related
      genes involved in enlarging the small intestine mainly through cell
      proliferation.

PMID- 24331528
TI  - Intraperitoneal administration attenuates thiazolidinedione-induced hepatic
      steatosis in KKAy mice with increased hepatic peroxisome proliferator-activated
      receptor (PPAR)gamma mRNA expression.
AB  - SUMMARY:  BACKGROUND: The pathogenesis of thiazolidinediones (TZDs)-induced
      hepatic steatosis in genetically obese diabetic mice has not been fully
      clarified. We herein examined the effects of pioglitazone treatment on liver
      histology. METHODS: To investigate TZDs-induced hepatic steatosis, KKAy mice were
      treated with pioglitazone orally or by intraperitoneal injection. RESULTS: Orally
      administered pioglitazone at 15 and/or 50 mg/kg/day worsened the hepatic
      steatosis in KKAy mice, however, the treatment at 50 mg/kg/day was not worse than
      that at 15 mg/kg/day. The basal expression of peroxisome proliferator-activated
      receptor (Ppar)gamma mRNA in the liver was upregulated to approximately 10% of
      that in white adipose tissue in these mice. Although no induction of hepatic
      Pparg mRNA by pioglitazone treatment was observed, the mRNA expression of the
      downstream lipogenic enzymes significantly increased. On the other hand,
      intraperitoneal administration of 15 mg/kg/day did not lead to deterioration of
      the hepatic steatosis of KKAy mice. Moreover, intraperitoneal administration led
      to an accompanying shift of fat distribution from intra-abdominal to subcutaneous
      adipose depots, and further increases in the serum adiponectin levels. In
      addition, a 5 day treatment without any change in body weight led to an obvious
      improvement in hepatic steatosis. CONCLUSIONS: Intraperitoneal administration of
      pioglitazone can act more strongly on intra-abdominal adipose tissues, and
      attenuates TZDs-induced hepatic steatosis in KKAy mice. The present study
      suggests that hepatic steatosis due to chronic treatment with TZDs is affected by
      the balance between endogenous lipogenesis in the liver and the lipid storage in
      adipose tissues, both occurring through PPARgamma.

PMID- 24331529
TI  - New C1q mutation in a Tunisian family.
AB  - Hereditary C1q deficiency (C1qD) is the most penetrant genetic factor
      predisposing to the development of lupus pathology with more than 93% of C1q
      deficient patients developing this autoimmune pathology throughout their life. It
      is a rare autosomal recessive deficiency, with only 67 cases reported so far
      including one Tunisian girl who died at the age of three from complications
      resulting from severe systemic lupus erythematosus. Although C1qD was confirmed
      in the serum of this patient using C1q ELISA and classical pathway specific
      functional assays, no DNA sample had been obtained from this patient. Here we
      report the analysis of sera and DNA of members of this patient's closer family.
      Our analysis identified a homozygous mutation within the gene encoding the C
      chain of C1q leading to a deficiency of C1q in an older sister of our original
      patient. This mutation, termed g.5580G4C, represents a single basepair
      substitution in exon 1 of the C1q C chain gene which changes the codon of Gly61
      to Arg 61. Amongst the other 14 mutations leading to C1qD, g.5580G4C represents
      the first reported transversion leading to human C1qD. 

PMID- 24331530
TI  - Acute coronary syndromes are associated with a reduction of VLA-1+ peripheral
      blood T cells and their enrichment in coronary artery plaque aspirates.
AB  - Memory T cells producing interferon (IFN)gamma and expressing very late antigen-1
      (VLA-1) integrin collagen receptors are found in carotid atherosclerotic plaques,
      suggesting their involvement in coronary artery disease (CAD) as well. To
      determine the role of VLA-1+ T cells in CAD percent of CD3+ T cells binding
      monoclonal antibodies (mAb) to VLA-1 in peripheral blood (PB), and in coronary
      plaque material aspirated during coronary arterography and arterial blood, were
      analyzed in a cohort of 117 patients with CAD and 34 controls without CAD. % VLA
      1+ T cells in PB was 0.63 +/- 0.09% in controls compared to 0.96 +/- 0.95% in
      patients with CAD (p<0.009). The increase was due to a marked elevation of % VLA
      1+ T cells in stable CAD (1.6 +/- 0.27%) whereas % VLA-1+ T cells during acute
      coronary syndromes (ACS) and in patients with ischemia by thalium SPECT scan had
      significantly lower levels. % VLA-1+ T cells in coronary artery plaque material
      aspirated during therapeutic angiography in patients with ACS was significantly
      higher than in arterial blood (1.39 +/- 0.96% vs 0.75 +/- 0.84%, p<0.035, n=3).
      Thus, % VLA-1+ T cells increases in the PB during stable CAD but decreases in
      ACS. The finding of their enrichment in coronary blood containing atherosclerotic
      plaque aspirates suggests that a shift of VLA-1+ T cells from blood to
      atherosclerotic plaques may play a role in plaque instability in patients with
      ACS.

PMID- 24331531
TI  - Molecular epidemiology of enteroviruses associated with hand, foot, and mouth
      disease in the mainland of China.

PMID- 24331532
TI  - Molecular epidemiological characteristics of Streptococcus pyogenes strains
      involved in an outbreak of scarlet fever in China, 2011.
AB  - OBJECTIVE: To investigate molecular characterization of streptococcus pyogenes
      isolates involved in an outbreak of scarlet fever in China in 2011. METHODS:
      Seventy-four Streptococcal pyogenes involved in an outbreak of scarlet fever were
      isolated from pediatric patients in the areas with high incidence in China from
      May to August of 2011. Emm genotyping, pulsed-field gel electrophoresis (PFGE),
      superantigen (SAg) genes and antimicrobial susceptibility profiling were analyzed
      for these isolates. RESULTS: A total of 4 different emm types were identified.
      Emm12 was the most prevalent type which contained four predominating PFGE
      patterns corresponding to four different virulence and superantigen profiles.
      Emm12 (79.7%) and emm1 (14.9%) accounted for approximately 94% of all the
      isolates. The speA gene was all negative in emm12 isolates and positive in emm1
      isolates. All strains were resistant to erythromycin, and 89.4% of them were
      resistant to erythromycin, tracycline, and clindamycin simultaneously.
      CONCLUSION: Several highly diversified clones with a high macrolide resistance
      rate comprise a predominant proportion of circulating strains, though no new emm
      type was found in this outbreak. The data provide a baseline for further
      surveillance of scarlet fever, which may contribute to the explanation of the
      outbreak and development of a GAS vaccine in China.

PMID- 24331533
TI  - Analysis of allergens in 5 473 patients with allergic diseases in Harbin, China.
AB  - OBJECTIVE: To analyze the allergic status to common inhalant allergens and food
      allergens in clinical patients in Harbin in northeastern China and provide
      evidence to develop the prevention strategy of allergic disease. METHODS: The
      data were collected from 5 473 patients with clinical suspected allergic diseases
      seeking medical care in the Second Affiliated Hospital of Harbin Medical
      University. Among these patients, 2 530 (46.2%) were males aged 0-86 years, the
      youngest was only 1 month old and 2 579 (47.1%) were young children and
      teenagers. The serum specific Immunoglobulin E (sIgE) to 14 kinds of common
      allergens and serum total IgE were detected by using AllergyScreen test (Mediwiss
      Analytic GmbH, Moers, Germany). RESULTS: In 5 473 subjects the positive rate of
      sIgE was 33.1% (n=1 813). Cow milk (6.9%) and wheat (3.1%) were the most common
      food allergens, followed by house dust mite mix (12.5%) and mould mix (9.4%) and
      the age and gender specific differences in the positive rate were significant.
      For the children aged <7 years the positive rates to cow milk, beef-mutton, and
      egg white/egg yolk were high, but the positive rates to house dust mite mix,
      ragweed estragon, and mould mix were low (P<0.05). For the adults the positive
      rates to aeroallergens were high while the rates to food allergens were low.
      CONCLUSION: The results from this study showed that the food allergens in Harbin
      had geographic characteristics, which support the viewpoint that the environment
      factors play an important role in the incidence of allergic diseases. Also, the
      detection of sIgE and total IgE are essential to identify relevant allergens for
      the purpose of early diagnosis, management and prevention of allergic disease.

PMID- 24331534
TI  - Novel species including Mycobacterium fukienense sp. is found from tuberculosis
      patients in Fujian Province, China, using phylogenetic analysis of Mycobacterium
      chelonae/abscessus complex.
AB  - OBJECTIVE: To identify the novel species 'Mycobacterium fukienense' sp. nov of
      Mycobacterium chelonae/abscessus complex from tuberculosis patients in Fujian
      Province, China. METHODS: Five of 27 clinical Mycobacterium isolates (Cls) were
      previously identified as M. chelonae/abscessus complex by sequencing the hsp65,
      rpoB, 16S-23S rRNA internal transcribed spacer region (its), recA and sodA house
      keeping genes commonly used to describe the molecular characteristics of
      Mycobacterium. Clinical Mycobacterium isolates were classified according to the
      gene sequence using a clustering analysis program. Sequence similarity within
      clusters and diversity between clusters were analyzed. RESULTS: The 5 isolates
      were identified with distinct sequences exhibiting 99.8% homology in the hsp65
      gene. However, a complete lack of homology was observed among the sequences of
      the rpoB, 16S-23S rRNA internal transcribed spacer region (its), sodA, and recA
      genes as compared with the M. abscessus. Furthermore, no match for rpoB, sodA,
      and recA genes was identified among the published sequences. CONCLUSION: The
      novel species, Mycobacterium fukienense, is identified from tuberculosis patients
      in Fujian Province, China, which does not belong to any existing subspecies of M.
      chelonea/abscessus complex.

PMID- 24331535
TI  - Resveratrol induces apoptosis and autophagy in T-cell acute lymphoblastic
      leukemia cells by inhibiting Akt/mTOR and activating p38-MAPK.
AB  - OBJECTIVE: To explore the effects of resveratrol-induced apoptosis and autophagy
      in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular
      mechanisms. METHODS: The anti-proliferation effect of resveratrol-induced,
      apoptosis and autophagy on T-ALL cells were detected by using MTT test,
      immunofluorescence, electronic microscope, and flow cytometry, respectively.
      Western blotting was performed for detecting changes of apoptosis-associated
      proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR,
      p70S6K, 4E-BP1, and p38-MAPK. RESULTS: Resveratrol inhibited the proliferation
      and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent
      manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin
      dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and
      cyclin D1. Western blotting revealed that resveratrol significantly decreased the
      expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the
      expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved
      caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3
      I and Beclin 1 was also detected. Furthermore, resveratrol induced significant
      dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific
      phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy
      was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was
      enhanced. CONCLUSION: Our findings have suggested that resveratrol induces cell
      cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting
      Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy
      might play a role as a self-defense mechanism in T-ALL cells treated by
      resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may
      serve as a promising strategy for resveratrol induced apoptosis and can be used
      as adjuvant chemotherapy for T-ALL.

PMID- 24331536
TI  - Echinococcus granulosus: suitable in vitro protoscolices culture density.

PMID- 24331537
TI  - Efficient expression and purification of Fc-fragment-binding domain and its
      application to immunoglobulin G purification.

PMID- 24331538
TI  - Selenium supplementation alleviates autoimmune thyroiditis by regulating
      expression of TH1/TH2 cytokines.

PMID- 24331540
TI  - Role of Fas/FasL pathway-mediated alveolar macrophages releasing inflammatory
      cytokines in human silicosis.

PMID- 24331539
TI  - Acrylamide alters cytoskeletal protein level in rat serum.

PMID- 24331541
TI  - HPV infection among Uygur women in a rural area of Hetian Prefecture, Xinjiang
      Uygur Autonomous Region, China.

PMID- 24331542
TI  - Optimized reimbursement scheme of China's new cooperative medical system using
      Monte Carlo Simulation.

PMID- 24331544
TI  - Toll-like receptor 4 regulates chronic stress-induced visceral pain in mice.
AB  - BACKGROUND: Functional gastrointestinal disorders, which have visceral
      hypersensitivity as a core symptom, are frequently comorbid with stress-related
      psychiatric disorders. Increasing evidence points to a key role for toll-like
      receptor 4 (TLR4) in chronic pain states of somatic origin. However, the central
      contribution of TLR4 in visceral pain sensation remains elusive. METHODS: With
      pharmacological and genetic approaches, we investigated the involvement of TLR4
      in the modulation of visceral pain. The TLR4-deficient and wild-type mice were
      exposed to chronic stress. Visceral pain was evaluated with colorectal
      distension. Protein expression levels for TLR4, Cd11b, and glial fibrillary
      acidic protein (glial cells markers) were quantified in the lumbar region of the
      spinal cord, prefrontal cortex (PFC), and hippocampus. To evaluate the effect of
      blocking TLR4 on visceral nociception, TAK-242, a selective TLR4 antagonist, was
      administered peripherally (intravenous) and centrally (intracerebroventricular
      and intra-PFC) (n = 10-12/experimental group). RESULTS: The TLR4 deficiency
      reduced visceral pain and prevented the development of chronic psychosocial
      stress-induced visceral hypersensitivity. Increased expression of TLR4 coupled
      with enhanced glia activation in the PFC and increased levels of proinflammatory
      cytokines were observed after chronic stress in wild-type mice. Administration of
      a TLR4 specific antagonist, TAK-242, attenuated visceral pain sensation in
      animals with functional TLR4 when administrated centrally and peripherally.
      Moreover, intra-PFC TAK-242 administration also counteracted chronic stress
      induced visceral hypersensitivity. CONCLUSIONS: Our results reveal a novel role
      for TLR4 within the PFC in the modulation of visceral nociception and point to
      TLR4 as a potential therapeutic target for the development of drugs to treat
      visceral hypersensitivity.

PMID- 24331545
TI  - Rapid mood-elevating effects of low field magnetic stimulation in depression.
AB  - BACKGROUND: We previously reported rapid mood elevation following an experimental
      magnetic resonance imaging procedure in depressed patients with bipolar disorder
      (BPD). This prompted the design, construction, and testing of a portable
      electromagnetic device that reproduces only the rapidly oscillating (1 kHz, <1
      V/m) electromagnetic field of the experimental procedure, called low field
      magnetic stimulation (LFMS). METHODS: We used a randomized, double blind, sham
      controlled treatment protocol to study the effects of LFMS in a large group of
      stably medicated, depressed patients with either BPD (n = 41) or major depressive
      disorder (n = 22). Subjects received a single, 20-minute treatment. Change in
      mood was assessed immediately afterward using a visual analog scale (VAS), the 17
      item Hamilton Depression Rating Scale (HDRS-17), and the Positive and Negative
      Affect Schedule scales. RESULTS: Substantial improvement (>10% of baseline) in
      mood was observed following LFMS treatment relative to sham treatment for both
      diagnostic subgroups for our primary outcomes, the VAS and the HDRS-17. These
      differences were not statistically significant in primary analyses stratifying by
      diagnosis but were significant in secondary analyses combining data across the
      two diagnostic groups (p = .01 VAS, p = .02 HDRS-17). Rapid improvement in mood
      was also observed using the Positive and Negative Affect Schedule scales as
      secondary measures (positive affect scale p = .02 BPD, p = .002 combined group).
      A finite element method calculation indicates a broad penetration of the LFMS
      electric field throughout the cerebral cortex. CONCLUSIONS: Low field magnetic
      stimulation may produce rapid changes in mood using a previously unexplored range
      of electromagnetic fields.

PMID- 24331546
TI  - Type 2 diabetes mellitus: a potentially modifiable risk factor for neurochemical
      brain changes in bipolar disorders.
AB  - BACKGROUND: Neuroimaging changes in bipolar disorder (BD) may be secondary to the
      presence of certain clinical factors. Type 2 diabetes mellitus (T2DM) damages the
      brain and frequently co-occurs with BD. Studying patients with both T2DM and BD
      could help identify preventable risk factors for neuroimaging changes in BD.
      METHODS: We used 1.5T magnetic resonance spectroscopy to measure prefrontal N
      acetylaspartate (NAA), which is mainly localized in neurons, and total creatine
      (tCr), an energy metabolite, in 19 BD patients with insulin resistance/glucose
      intolerance (BD + IR/GI), 14 BD subjects with T2DM (BD + T2DM), 15 euglycemic BD
      participants, and 11 euglycemic, nonpsychiatric control. RESULTS: The levels of
      NAA and tCr were lowest among BD + T2DM, intermediate in the BD + IR/GI, and
      highest among the euglycemic BD and control subjects (F3,55 = 4.57, p = .006;
      F3,55 = 2.92, p = .04, respectively). Even the BD + IR/GI subjects had lower NAA
      than the euglycemic participants (t43 = 2.13, p = .04). Total Cr was associated
      with NAA (beta = .52, t56 = 5.57, p = .000001). Both NAA and tCr correlated with
      Global Assessment of Functioning scores (r46 = .28, p = .05; r46 = .48, p =
      .0004, respectively). CONCLUSIONS: T2DM, but also prediabetes, may be risk
      factors for prefrontal neurochemical alterations in BD. These changes were
      associated with poor psychosocial functioning and could indicate impaired energy
      metabolism. The findings emphasize the importance of improving diabetes care in
      BD and suggest potential options for treatment of neuroimaging alterations.

PMID- 24331547
TI  - Primary thromboprophylaxis in hospices: the association between risk of venous
      thromboembolism and development of symptoms.
AB  - CONTEXT: Venous thromboembolism (VTE) risk assessment for adults admitted to
      hospital is commonplace, but the utility of assessment tools in patients admitted
      to hospices or palliative care units and prediction of symptomatic VTE is
      unknown. OBJECTIVES: To investigate the relationship between risk of VTE and
      development of symptoms. METHODS: Retrospective consecutive admission, case-note
      data from seven U.K. hospices were collected during an evaluation of a VTE risk
      assessment protocol using the Pan Birmingham Cancer Network palliative-modified
      Thromboembolic Risk Factors (THRIFT) Consensus Group criteria and
      presence/absence of a temporary elevated risk (TER) of VTE. Symptoms/signs during
      admission consistent with possible VTE were documented. RESULTS: A total of 1164
      case-notes were analyzed (age range 23-99; men 627). THRIFT risk was high in 13%,
      medium in 83%, and low in 4%; a TER was identified in 24%. In the "clinically
      relevant group" (no contraindication, not anticoagulated), where primary
      thromboprophylaxis could have been prescribed (n = 528), TER and symptoms were
      associated (21% symptoms with TER vs. 9% symptoms without TER: Chi-squared, P <
      0.001). A high/moderate THRIFT score had a sensitivity of 98.4% (95% CI 91.3%
      99.9%) and specificity of 5.8% (95% CI 3.9%-8.3%). The TER assessment had a more
      evenly balanced sensitivity (41.9%; 95% CI 29.5%-55.2%) and specificity (79%; 95%
      CI 75.0%-82.6%). CONCLUSION: Hospice inpatients are at risk for VTE. TER alone is
      simpler to use and may be more useful in this population than the THRIFT but
      still has limitations regarding ability to predict symptoms.

PMID- 24331548
TI  - A comparative study of brain activation patterns associated with sexual arousal
      between males and females using 3.0-T functional magnetic resonance imaging.
AB  - Background In contrast to the previous studies using a 1.5-T magnetic resonance
      imaging system, our study was performed on a higher magnetic field strength, 3.0
      T, to gain more valuable information on the functional brain anatomy associated
      with visual sexual arousal for discriminating the gender difference by increasing
      the detection power of brain activation. METHODS: Twenty-four healthy subjects
      consisting of 12 males and 12 females underwent functional magnetic resonance
      imaging examination for this study. Brain activity was measured while viewing
      erotic videos. RESULTS: The predominant activation areas observed in males as
      compared with females included the hypothalamus, the globus pallidus, the head of
      the caudate nucleus, the parahippocampal gyrus, the amygdala and the septal area,
      whereas the predominant activation in females was observed in the anterior
      cingulate gyrus and the putamen. CONCLUSION: Our findings suggest that the brain
      activation patterns associated with visual sexual arousal are specific to gender.
      This gender difference in brain activation patterns is more remarkable at higher
      magnet field (3.0 T) than at 1.5 T.

PMID- 24331549
TI  - Can an active aging index (AAI) provide insight into reducing elder abuse? A case
      study in Rajshahi District, Bangladesh.
AB  - We use data from respondents aged 60 years and above, collected during April 2009
      in the Rajshahi district of Bangladesh, to examine whether high activeness, as
      captured by an AAI or in sub-domains, can help reduce the risk of elder abuse.
      The findings suggest that more than half of rural elderly and 14 percent of urban
      elderly were at some point abused. High activeness in health and security
      dimensions lowers the risk of being abused while those who are low active in
      community participation have the lowest risk of being abused in both rural and
      urban areas. Being literate (elderly with primary/secondary education) is
      revealed to be a significant factor that lowers the risk of abuse in both rural
      and urban areas. These results imply a need for educational programs that bolster
      positive and proper community interaction, in turn promoting a secure later life
      for elders, and reducing burden for families and society. High activeness in
      health and security dimensions should also be promoted to keep the elderly
      healthy and protect from abusive behavior. 

PMID- 24331550
TI  - Influence of veneer and cyclic loading on failure behavior of lithium disilicate
      glass-ceramic molar crowns.
AB  - OBJECTIVE: This in vitro study was designed to investigate the influence of the
      veneer and cyclic loading on the failure behavior of lithium disilicate glass
      ceramic (LDG) crowns on maxillary first molar. METHODS: Sixty-four LDG crowns
      were divided into 4 groups (n=16). Thirty-two monolithic crowns were fabricated
      from IPS e.max Press (M), and the remaining bilayered crowns using cut-back
      technique and conventional manual layering technique from IPS e.max Press/Ceram
      (B). Monolithic or bilayered crowns were subjected to single-load-to-fracture
      (SLF) testing using a universal testing machine, before (M1 and B1) and after
      exposure to sliding-contact fatigue (SCF) testing (M2 and B2), consisting of
      1,200,000 mechanical cycles (Fmax=98 N). Data were statistically analyzed using
      two-by-two factorial design ANOVA. Fractographic analysis was performed to
      determine the fracture modes of the failed specimens. RESULTS: The mean fracture
      load values (N+/-S.D.) for M1, B1, M2 and B2 were 2686+/-628 N, 1443+/-327 N,
      2133+/-578 N and 1464+/-419 N, respectively. Significant differences were found
      between the failure loads of all groups (P<0.001), except between groups B1 and
      B2. Bulk fracture initiating from the occlusal surface is the primary failure
      mode of monolithic and veneered LDG crowns. Cracking that initiated from core
      veneer interfacial defects and ultimately resulted in bulk fracture is another
      major failure origin of veneered all-ceramic crowns. SIGNIFICANCE: Veneer
      application resulted in significantly lower fracture load values compared to
      monolithic LDG crowns. Cyclic loading is an accelerating factor contributing to
      fracture for monolithic LDG crowns but not for bilayered ones.

PMID- 24331551
TI  - Foreword.

PMID- 24331552
TI  - The crucial contribution of veterinarians to conservation biology.
AB  - Conservation biology is a relatively new (began in the 1980s), value-based
      discipline predicated on the belief that biological diversity-from genes to
      populations to species to communities to ecosystems-is good and extinction is
      bad. Conservation biology grew from the recognition that the Earth has entered
      its sixth great extinction event, one that differs from previous great
      extinctions in that a single species-Homo sapiens-has caused this biodiversity
      crisis. A diverse, interacting set of variables drive current extinctions. As
      such, to succeed, conservation efforts usually require broad-based,
      interdisciplinary approaches. Conservationists increasingly recognize the
      importance of contributions by veterinary science, among many other disciplines,
      to collaborative efforts aimed at stemming the loss of biodiversity. We argue
      that, to improve success rates, many wildlife conservation programs must
      incorporate veterinarians as part of an interdisciplinary team to assess and
      address problems. Ideally, veterinarians who participate in conservation would
      receive specialized training and be willing to work as partners as part of a
      larger team of experts who effectively integrate their work rather than work
      independently (i.e., work as interdisciplinary, as opposed to multidisciplinary,
      teams, respectively). In our opinion, the most successful and productive projects
      involve interdisciplinary teams involving both biological and nonbiological
      specialists. Some researchers hold multiple degrees in biology and veterinary
      medicine or the biological and social sciences. These experts can often offer
      unique insight. We see at least 3 major areas in which veterinarians can
      immediately offer great assistance to conservation efforts: (1) participation in
      wildlife capture and immobilization, (2) leadership or assistance in addressing
      wildlife health issues, and (3) leadership or assistance in addressing wildlife
      disease issues, including using wildlife as sentinels to identify new and
      emerging diseases or epidemics of old diseases. We cover each of these main
      topics in detail.

PMID- 24331553
TI  - Polar bears: the fate of an icon.
AB  - Polar bears are one of the most iconic animals on our planet. Worldwide, even
      people who would never see one are drawn to these charismatic arctic ice hunters.
      They are the world's largest terrestrial carnivore, and despite being born on
      land, they spend most of their lives out on the sea ice and are considered a
      marine mammal. Current global studies estimate there are around 20,000 animals in
      some 19 discrete circumpolar populations. Aside from pregnant females denning in
      the winter months to give birth, the white bears do not hibernate. They spend
      their winters on the sea ice hunting seals, an activity they are spectacularly
      adapted for. Research on these animals is incredibly difficult because of the
      inhospitable surroundings they inhabit and how inaccessible they make the bears.
      For many years, the sum of our understanding of the natural history of polar
      bears came from tracks, scats, the remains of their kills, abandoned dens, and
      anecdotal observations of native hunters, explorers, and early biologists.
      Nonetheless, the last 40 years have seen a much better picture of their biology
      emerge thanks to, first, dedicated Canadian researchers and, later, truly
      international efforts of workers from many countries. Veterinarians have
      contributed to our knowledge of the bears by delivering and monitoring
      anesthesia, obtaining blood samples, performing necropsies, investigating their
      reproduction, conducting radiotelemetry studies, and examining their behavior.
      Recently, new technologies have been developed that revolutionize the study of
      the lives and natural history of undisturbed polar bears. These advances include
      better satellite radiotelemetry equipment and the development of remote
      controlled miniature devices equipped with high-definition cameras. Such new
      modalities provide dramatic new insights into the life of polar bears. The
      remarkable degree of specialized adaptation to life on the sea ice that allowed
      the bears to be successful is the very reason that the bears are so vulnerable to
      the effects of climate change. Polar bears have few alternatives if their habitat
      (the sea ice) and their access to their ringed seal prey rapidly disappear.
      Predictions that polar bears may be able to adjust and sustain themselves on
      alternative food sources are not based on reality. Spring breakup of the sea ice
      is happening much earlier as well as fall freezeup is getting later, thereby
      prolonging the open water period that the bears are shore bound. If trends
      continue and the ice continues to disappear, the effect on polar bears would be
      devastating. Veterinarians must stay involved in polar bear studies and in
      multidisciplinary conservation studies dealing with threatened and endangered
      species worldwide. On account of their training, veterinarians can offer a unique
      skill set that can provide access to a number of technologies critical to
      conservation efforts. The oath veterinarians take on graduation from veterinary
      school charges them to be sworn to the "conservation of animal resources" and in
      the education of the public. We are only as good as the oaths we keep.

PMID- 24331554
TI  - Veterinary assessment for free-ranging Eurasian Black Vulture (Aegypius monachus)
      chicks in southeastern Mongolia.
AB  - Working as a veterinarian in remote field locations can be physically and
      intellectually challenging. A collaborative multi-disciplinary approach is often
      required for successful data collection. Technologies and methodologies
      frequently need to be modified to work in these harsh field environments. This
      article will describe a collaboration in southeastern Mongolia collecting blood
      for sera analytes and physiologic data from Eurasian Black Vulture (Aegypius
      monachus) chicks during a tagging operation.

PMID- 24331555
TI  - Longline fishing (how what you don't know can hurt you).
AB  - Longline fishing utilizes monofilament lines that can be as much as 62 miles
      long. The line itself is buoyed by Styrofoam or plastic floats. Usually, at about
      every 100ft, a secondary line is attached and hangs down from the mainline. The
      lines are baited with mackerel, squid, or shark meat and have as many as 10,000
      hooks. Every 12-24 hours, the line is hauled in, mechanically rebaited, and set
      back into the water behind the vessel. The baited hooks can be seen by albatross
      and other seabirds as they are placed in the water or being hauled out. When the
      birds dive for the bait, they are hooked, dragged behind the fishing boat, and
      drown. Spectacularly nonselective, longline fishing techniques also hook many
      other forms of marine life-"bycatch" (sea turtles, seals, dolphins, penguins,
      sharks, and many other nontarget finfish). It is estimated that 300,000 seabirds
      (including 100,000 albatross) die on longlines each year. Albatross are among the
      longest-lived birds. They can live up to 60 years and some species do not start
      breeding until they are 10 years old. They have a low reproductive rate and many
      species only breed every other year. In addition, a species like the Wandering
      Albatross (Diomedea exulans) rears its chicks for an average of more than 270
      days. Albatross pair for life and may take years to find a new partner if their
      mate is killed. Owing to their incredibly low reproductive rate, albatross are
      particularly vulnerable to longline fishing. Currently, it is believed that 4
      albatross drown per 100,000 hooks set. This is more than 400 birds a week. The
      current mortality rate for adult birds is not sustainable and for some species,
      the birds are dying faster that they can repopulate. Currently, 19 of the world's
      22 albatross species are threatened with extinction. This year longline fishing
      ships will set 10 billion hooks worldwide. Various mitigation measures (bird
      scaring lines, weighted, faster-sinking line, setting lines deeper out of the
      bird's sight, reduction in the amount of offal discarded from fishing boats,
      night fishing, and restriction of longline operations from areas where nesting
      and foraging birds are congregated during the breeding season, among others) have
      been proposed and attempted. There is no one panacea for the effects of
      longlining and mitigation efforts are most successful when used in combination.
      Some of these mitigation measures have shown very promising results. Some experts
      feel that government legislation, regulation, and enforcement in conjunction with
      incentives for the fishing industry to incorporate and implement mitigating
      techniques have the best chance in ameliorating the problem. The public is
      surprisingly unaware of this wanton and wasteful exploitation of the ocean's
      resources, and the worldwide demand for seafood continues to rise. Meanwhile,
      globally, fishermen voice the same complaints: fewer fish, smaller fish, shorter
      fishing seasons, bizarre developments in their seasonal appearance and dispersal,
      and fewer overall species seen. These are all the classic signs of overfishing.
      Each year it is estimated that some 90 million tons of wild fish are harvested
      from our planet's oceans. Nearly 30 million tons of this is discarded as the
      incidental bycatch of nontarget species. If international curbs are not placed
      upon wasteful fishing practices, we are doomed to learn a painful maxim. "The
      ocean is not infinite." Veterinarians must become involved in worldwide
      conservation efforts, acting locally, while thinking globally.

PMID- 24331556
TI  - A review of the proposed reintroduction program for the Far Eastern leopard
      (Panthera pardus orientalis) and the role of conservation organizations,
      veterinarians, and zoos.
AB  - The Amur leopard is at the point of extinction. At present there are fewer than
      35 in the wild. Their natural habitat ranges from China to the North Korean
      peninsula to Primorsky Krai in Russia. A reintroduction plan has been proposed to
      increase the population in the wild; however, this proposed plan still has many
      questions to be answered as to how effective it will be. The main objective is to
      reintroduce animals from a select group within the Far Eastern leopard programme
      or the Species Survival programme, which consist of leopards from select
      populations in the Northern Hemisphere. Zoos are central to the success of this
      plan, providing suitable breeding pairs to breed animals for reintroduction and
      also raising much needed funds to finance the project. Zoos are also central in
      educating the public about the critical status of the Amur leopard and other
      endangered animals of the world. Veterinary surgeons, by the very nature of their
      professional skills, are at the forefront of this seemingly endless battle
      against extinction of thousands of species that are critical to maintaining the
      balance of our fragile ecosystem. Veterinarians can analyze the health risks and
      health implications of reintroduction on the animals to be reintroduced and also
      on the native population. A world without large cats is a world hard to imagine.
      If we look closer at the implications of extinction, we see the domino effect of
      their loss and an ecosystem out of control.

PMID- 24331557
TI  - Additional observations and notes on the natural history of the prairie
      rattlesnake (Crotalus viridis) in Colorado.
AB  - On account of their unique anatomy, physiology, natural history, ecology, and
      behavior, rattlesnakes make ideal subjects for a variety of different scientific
      disciplines. The prairie rattlesnake (Crotalus viridis) in Colorado was selected
      for investigation of its relationship to colonies of black-tailed prairie dogs
      (Cynomys ludovicianus) with regard to spatial ecology. A total of 31 snakes were
      anesthetized and had radiotransmitters surgically implanted. In addition, at the
      time of their capture, all snakes underwent the following: (1) they had bacterial
      culture taken from their mouths for potential isolation of pathogenic bacteria;
      (2) similarly, they had cloacal bacterial cultures taken to assess potentially
      harmful bacteria passed in the feces; and (3) they had blood samples drawn to
      investigate the presence of any zoonotic agents in the serum of the snakes. The
      results of the study and their implications are discussed here. Traditionally, a
      low incidence of bacterial wound infection has been reported following snakebite.
      Nevertheless, the oral cavity of snakes has long been known to house a wide
      variety of bacterial flora. In our study, 10 different bacterial species were
      isolated from the mouths of the rattlesnakes, 6 of which are capable of being
      zoonotic pathogens and inducing human disease. More studies are necessary to see
      why more rattlesnake bites do not become infected despite the presence of such
      pathogenic bacteria. The results of fecal bacteria isolated revealed 13 bacterial
      species, 12 of which can cause disease in humans. Of the snakes whose samples
      were cultured, 26% were positive for the presence of the pathogen Salmonella
      arizonae, one of the causative agents of reptile-related salmonellosis in humans.
      It has long been reported that captive reptiles have a much higher incidence than
      wild, free-ranging species. This study shows the incidence of Salmonella in a
      wild, free-ranging population of rattlesnakes. In addition, Stenotrophomonas
      maltophilia was isolated. This bacterium is associated with wound and soft tissue
      infections that can lead to sepsis, endocarditis, meningitis, and peritonitis. In
      addition, this bacterium has been increasingly implicated as an opportunistic
      pathogen to humans during pregnancies, hospitalizations, malignancies and
      chemotherapy, chronic respiratory diseases, and presurgical endotracheal
      intubation. Furthermore, S. maltophilia has an intense resistance to broad
      spectrum antibiotics, the results of our study showed the bacterium was resistant
      to multiple antibiotics. Our results indicate that anyone working with snake
      feces, dead skin, or their carcasses must follow reasonable hygiene protocols.
      Rattlesnakes tested for West Nile antibodies had positive results but these were
      invalidated owing to possible cross-reactivity with other unknown viruses,
      interference with snake serum proteins, and the fact that the test was not
      calibrated for rattlesnake serum. Still, the interesting implication remains,
      should we be regularly testing these animals as sentinels against potentially
      zoonotic diseases. The results of this study clearly show the value of
      veterinarians in a multidisciplinary study of this sort and the particular skill
      set they can offer. Veterinarians must get involved in conservation studies if
      the biodiversity of the planet is to be preserved.

PMID- 24331558
TI  - How to get involved (what veterinarians can do to make a difference).

PMID- 24331559
TI  - Oral-maxillofacial surgery residency training--practice pattern mismatch?

PMID- 24331560
TI  - Mandibular reconstruction using intraoral microvascular anastomosis following
      removal of an ameloblastoma.

PMID- 24331561
TI  - Cone-beam computed tomographic incidental findings--a cause for worry.

PMID- 24331562
TI  - Three-dimensional virtual mandibular reconstruction.

PMID- 24331563
TI  - Letter to the editor.

PMID- 24331564
TI  - Interdental osteotomies induce regional acceleratory phenomenon and accelerate
      orthodontic tooth movement.
AB  - PURPOSE: Although it has been revealed clinically that double-jaw orthognathic
      surgery induces a systemic increase in the baseline bone turnover and
      subsequently accelerates postoperative orthodontic tooth alignment, it is not
      clear whether less extensive osteotomy, such as interdental osteotomy, would be
      intensive enough to accelerate postoperative orthodontic tooth alignment.
      MATERIALS AND METHODS: Twelve adult male beagle dogs were randomly assigned to 2
      groups. The sham control group (n = 6) received orthodontic tooth alignment of
      the maxillary incisors, and the experimental group (n = 6) received orthodontic
      tooth alignment of the maxillary incisors and interdental osteotomies between the
      maxillary third incisor and canine on both sides concurrent with the beginning of
      orthodontic tooth alignment. The duration of orthodontic tooth alignment was 3
      months in both groups. Cone-beam computed tomography scans of the maxilla, dental
      casts, blood samples, and gingival crevicular fluid (GCF) of the maxillary
      incisors were taken immediately before orthodontic tooth alignment (T0) and 1
      week (T1) and 1 (T2), 2 (T3), and 3 (T4) months after beginning orthodontic tooth
      alignment. They were analyzed for changes in the interdental alveolar bone gray
      scale (osteoporosity) of the maxillary incisors, irregularity index (rate of
      orthodontic tooth alignment), and bone-specific alkaline phosphatase (bALP, a
      biomarker of osteoblastic activity) and C-terminal telopeptide of type I collagen
      (ICTP, a biomarker for osteoclastic activity) in the serum and GCF samples from
      T0 to T4. The data were analyzed statistically for inter- and intragroup
      differences. RESULTS: The rate of orthodontic tooth alignment for the
      experimental group was significantly greater and twofold that of the sham control
      group at T1, T2, T3, and T4. The serum-bALP, serum-ICTP, GCF-bALP, GCF-ICTP, and
      osteoporosity remained similar from T0 to T4 in the sham control group. In
      contrast, GCF-bALP increased two- to threefold from T1 to T4, and GCF-ICTP
      increased fivefold at T1 and then gradually decreased from T2 to T4. The
      interdental osteoporosity significantly increased from T1 to T4, but the serum
      bALP and serum-ICTP levels remained similar, without significant changes in the
      experimental group. CONCLUSIONS: Interdental osteotomy induced a regional, but
      not a systemic, acceleratory phenomenon and was intensive enough to accelerate
      postoperative orthodontic tooth alignment twofold. The intensity of the increase
      in the bone turnover rate and osteoporosity might depend on the extent of the
      osteotomy.

PMID- 24331565
TI  - Hydroxyapatite and collagen combination-coated dental implants display better
      bone formation in the peri-implant area than the same combination plus bone
      morphogenetic protein-2-coated implants, hydroxyapatite only coated implants, and
      uncoated implants.
AB  - PURPOSE: The objective of this study was to compare peri-implant bone formation
      among uncoated (UC), hydroxyapatite (HA), collagen plus HA (CH), and collagen,
      HA, plus bone morphogenetic protein-2 (BMP-2) implant groups. MATERIALS AND
      METHODS: Implants in the UC group had acid-etched surfaces. The surface coating
      was applied using the aerosol deposition method. The coated surfaces were
      examined by scanning electron microscopy, x-ray diffraction (XRD), and Fourier
      transformed infrared absorption analysis. Subsequently, 6 implants from each
      group (total, 24 implants) were installed in the tibias of rabbits. The animals
      were sacrificed at 6 weeks after implant installation. Peri-implant bone
      formation and bone-to-implant contact (BIC) were measured in histologic sections.
      Significant differences among groups were evaluated using analysis of variance.
      RESULTS: Based on the measured XRD patterns, there was a characteristic HA phase
      (International Centre for Diffraction Data [ICDD], 086-0740) coated on the
      titanium (ICDD, 089-3725). Subsequent coating processes for collagen and BMP-2
      did not display additional diffraction peaks, but maintained the diffraction
      patterns of the HA-coated titanium. The presence of collagen was verified by
      infrared absorption analysis. When comparing these modifications with UC
      surfaces, only the CH coating displayed significantly greater peri-implant bone
      formation and BIC (P = .003 and P < .001, respectively). Adding BMP-2 to the
      implant surface did not produce any advantage compared with the CH coating.
      CONCLUSIONS: In this study, the CH group displayed significantly greater new bone
      formation and BIC than the other groups. There was no significant difference
      among the other groups.

PMID- 24331566
TI  - Effect of indomethacin on surface treatment and intracanal dressing of replanted
      teeth in dogs.
AB  - PURPOSE: This study evaluated the healing process of teeth replanted after root
      treatment and intracanal dressing with indomethacin alone or indomethacin with
      calcium hydroxide (Ca[OH]2). MATERIALS AND METHODS: Through a case-control study,
      24 teeth of 6 adult dogs were extracted, dried, and divided into 4 groups
      according to the root surface treatment protocols performed before replantation
      and the intracanal medication used after replantation. In group 1 (negative
      control), root surfaces were treated by immersion in a 0.9% saline solution and
      then replanted. In the other groups, the roots were immersed for 10 minutes in
      Ca(OH)2 (group 2), indomethacin (group 3), or a solution of indomethacin and
      Ca(OH)2 (group 4). After 2 weeks, group 1 teeth were subjected to single-visit
      root canal treatment and obturation with gutta-percha and sealer consisting of
      zinc oxide and eugenol. The teeth in the other groups were subjected to
      intracanal dressing with the same material used for immersion. After an
      additional period of 28 weeks, the animals were euthanized and the jaws
      containing the replanted teeth were processed for histologic analysis.
      Histometric values were statistically analyzed, with significance set at a P
      value less than or equal to .05. RESULTS: Group 1 exhibited significantly more
      normal periodontium than group 4 (P = .02). Total resorption was greater in group
      4 than in group 1 (P = .02). No statistically significant difference in the
      percentage of surface resorption or in total inactive resorption was observed
      between the groups. CONCLUSIONS: The findings of this study suggest that
      intracanal dressing and topical root treatment with Ca(OH)2 with or without
      indomethacin is not recommended for teeth dried for 50 minutes, but the use of
      indomethacin alone as root surface treatment for delayed tooth replantation
      deserves further study using longer drying periods. In addition, the present
      results suggest that a single-visit root canal, performed up to 2 weeks after
      replantation, might be indicated for teeth dried for up to 50 minutes.

PMID- 24331567
TI  - Submental fat transfer: an approach to enhance soft tissue conditions in patients
      with submental lipomatosis after orthognathic surgery.
AB  - Soft tissue changes after orthognathic surgery and their effects on the esthetic
      appearance of the patient can be the most challenging and sometimes undesired
      parts of this procedure. Although the soft tissue profile is improved in many
      orthognathic surgeries, suboptimal soft tissue changes may necessitate some
      special interventions. To overcome these problems, the authors present a
      technique based on transferring the submental fat (in patients with submental
      lipomatosis) to the lips, paranasal areas, or other sites of the face instead of
      discarding it. According to this technique, in patients with submental
      lipomatosis, submental fat can be used not only to compensate some of the
      unpleasant soft tissue effects of orthognathic procedures (eg, thinning of the
      upper lip after mandibular setback), but also to improve pre-existing soft tissue
      problems, which may be worse after orthognathic surgeries (eg, a poor neck and
      chin profile). Although submental fat liposuction is a traditional technique to
      improve the neck and chin profile, the present technique is based on transferring
      the harvested fat to other sites of the face (lips, paranasal areas, etc) instead
      of discarding it. 

PMID- 24331568
TI  - Does upper premolar extraction affect the changes of pharyngeal airway volume
      after bimaxillary surgery in skeletal class III patients?
AB  - PURPOSE: The purpose of this study was to assess the pharyngeal airway volume
      change after bimaxillary surgery in patients with skeletal Class III malocclusion
      and evaluate the difference in postoperative pharyngeal airway space between
      upper premolar extraction cases and nonextraction cases. MATERIALS AND METHODS:
      Cone-beam computed tomographic scans were obtained for 23 patients (13 in
      extraction group and 10 in nonextraction group) who were diagnosed with
      mandibular prognathism before surgery (T0) and then 2 months (T2) and 6 months
      after surgery (T3). Using InVivoDental 3-dimensional imaging software, volumetric
      changes in the pharyngeal airway space were assessed at T0, T2, and T3. The
      Wilcoxon signed-rank test was used to determine whether there were significant
      changes in pharyngeal airway volume between time points. The Mann-Whitney U test
      was used to determine whether there were significant differences in volumetric
      changes between the extraction and nonextraction groups. RESULTS: Volumes in all
      subsections of the pharyngeal airway were decreased (P < .05) except for changes
      in the oropharyngeal airway volume in the nonextraction group from T0 to T2.
      There were significant differences between the extraction and nonextraction
      groups in the changes of oro- and total pharyngeal airway volumes from T0 to T3.
      CONCLUSION: The null hypothesis was rejected. The extraction of upper premolars
      rather than nonextraction decreased the pharyngeal airway space more in patients
      with mandibular prognathism who planned to have bimaxillary surgery.

PMID- 24331569
TI  - Change in inferior sclera exposure following Le Fort I osteotomy in patients with
      midfacial retrognathia.
AB  - PURPOSE: For facial esthetic reasons, no sclera should be exposed above or below
      the irises when the head of a patient who has a normal skeletal pattern is in a
      neutral position and the eyelids are in a relaxed position. This study evaluated
      the decrease in sclera exposure after maxillary advancement or impaction in
      patients with midfacial hypoplasia. PATIENTS AND METHODS: Forty-seven consecutive
      patients (24 male, 23 female) who underwent Le Fort I osteotomy were included.
      The patients were divided into 2 groups according to type of maxillary movement:
      group I underwent maxillary advancement (n = 23) and group II underwent maxillary
      advancement and impaction surgery (n = 24). Standardized preoperative and 6-month
      postoperative photographs of the frontal view of patients were evaluated using
      Adobe Photoshop CS5. The proportion of inferior sclera exposure to eye height was
      determined, and the proportional difference between the preoperative and
      postoperative orbital views was statistically analyzed. RESULTS: The proportion
      of inferior sclera exposure to eye height decreased by a ratio of 0.07 (P = .001)
      in the right and left eyes of the 47 patients, with an average maxillary
      advancement of 6.1 mm. The proportion of inferior sclera exposure to eye height
      of the right and left eyes decreased from 0.1 to 0.02 and from 0.09 to 0.02,
      respectively, in group I (P = .001). The proportion of inferior sclera exposure
      to eye height decreased in group II by a ratio of 0.06 in the right and left eyes
      (P = .001). CONCLUSION: Inferior sclera exposure in patients with midfacial
      hypoplasia and retrognathia decreases significantly in accordance with the change
      in the lower eyelid position after maxillary advancement or impaction surgeries.

PMID- 24331570
TI  - Navigation-assisted mandibular body distraction osteogenesis: a preliminary study
      in goats.
AB  - PURPOSE: The purpose of the present study was to evaluate the accuracy of
      navigation-assisted distraction osteogenesis of the mandible in a goat model.
      MATERIALS AND METHODS: Six adult goats were included in the present study. A 3
      dimensional (3D) image was reconstructed by performing computed tomography (CT)
      scans in 0.625-mm slices after placement of 5 maxillary marking screws and
      intermaxillary fixation with a prefabricated occlusal splint using the TBNavis
      CMFS navigation system (Multifunctional Surgical Navigation System, Shanghai,
      China). Simulation distraction was performed to lengthen a unilateral mandibular
      body by 10 mm. Image-guided distraction osteogenesis was performed on the goat
      hemimandibles according to the preoperative planning. 3D skeletal measurements
      from the simulation were compared with those taken from the CT scans at 3 months
      postoperatively. RESULTS: Navigation-assisted distraction osteogenesis was
      successfully performed in all 6 goat hemimandibles. The accuracy of the
      intraoperative registration was within 1 mm. The hemimandible was lengthened a
      mean of 10.02 mm (range 9.89 to 10.12). No significant differences were found
      between the simulation distraction and postoperative 3D measurements (P > .05).
      CONCLUSIONS: Navigation-assisted distraction osteogenesis of the mandible in the
      goat model can be performed with high accuracy using the TBNavis-CMFS navigation
      system.

PMID- 24331571
TI  - A huge malignant perivascular epithelioid cell tumor (PEComa) of the uterine
      cervix and vagina.
AB  - Perivascular epithelioid cell tumors (PEComas) are a family of rare mesenchymal
      neoplasms, including angiomyolipoma, clear-cell "sugar" tumor of the lung and
      extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor
      of the falciform ligament/ligamentum teres, and clear-cell tumors at various
      other anatomic sites. These tumors are characterized by a proliferation of
      epithelioid cells with clear to eosinophilic cytoplasm, perivascular
      distribution, and coexpression of myogenic and melanocytic markers. PEComas show
      a female predominance, occur with some frequency in the gynecological tract, and
      have an unpredictable biological behavior. We report a case of a huge malignant
      PEComa arising from the uterine cervix and vagina. To the best of our knowledge,
      only 6 cases of PEComa in the cervix and 2 cases in the vagina have been reported
      in the literature. 

PMID- 24331572
TI  - Durable complete remission from castration-resistant prostate cancer with
      sipuleucel-T after estrogen withdrawal.

PMID- 24331573
TI  - Lymphovascular invasion in high grade T1 bladder cancer: are more aggressive
      treatments needed?

PMID- 24331574
TI  - Neutrophil-to-lymphocyte ratio as a novel independent prognostic factor in
      urothelial carcinoma.

PMID- 24331575
TI  - Clinical outcome of stereotactic radiosurgery for central nervous system
      metastases from renal cell carcinoma.
AB  - BACKGROUND: Current treatment modalities for central nervous system (CNS)
      metastases from renal cell cancer (RCC) include surgical resection, stereotactic
      radiosurgery (SRS), and whole-brain radiotherapy. Existing studies describing
      treatment outcomes for CNS metastases include multiple tumor types and thus
      provide little insight into how RCC CNS metastases respond to these modalities.
      MATERIALS AND METHODS: RCC patients with brain metastases treated with SRS at the
      Cleveland Clinic between 1996 and 2010 were retrospectively identified.
      Radiosurgery and systemic therapy characteristics were recorded. Patients were
      followed up radiographically at 1 to 2 months after radiosurgery and every 3 to 6
      months thereafter with magnetic resonance imaging scans. RESULTS: Of the 166
      patients identified, local control was obtained in 90% of patients. In 38% of
      patients there were additional distant CNS metastases at a median of 12.8 months
      (95% CI, 8.5-21.1) after SRS. The median time to progression (either local or
      distant) was estimated to be 9.9 months (95% CI, 5.9-12.9). Higher (> 2.5) RCC
      specific graded prognostic assessment (GPA) score was the only factor examined
      that was found to be a significant prognostic factor for improved outcome (P =
      .02); however, there was some suggestion that a single target lesion (P = .07)
      and age >= 60 years (P = .07) may also be associated with better CNS control.
      CONCLUSION: Stereotactic radiosurgery for a limited number of CNS metastases from
      RCC is associated with excellent local control and is an effective if not
      preferred treatment modality.

PMID- 24331576
TI  - EORTC progression score identifies patients at high risk of cancer-specific
      mortality after radical cystectomy for secondary muscle-invasive bladder cancer.
AB  - BACKGROUND: The aim of this study was to develop a risk stratification of
      patients with muscle-invasive bladder cancer (MIBC) after radical cystectomy
      (RC). For this purpose, we compared the cancer-specific mortality (CSM) of
      patients with primary MIBC and patients with secondary MIBC in different risk
      groups according to the European Organisation for Research and Treatment of
      Cancer (EORTC) progression score. PATIENTS AND METHODS: The records of 521
      consecutive patients treated with RC for clinical MIBC according to transurethral
      resection of bladder cancer (TURBT) diagnosis were reviewed. Of the 521 patients,
      399 (76.6%) had primary MIBC (study group 1 [SG1]) and 122 (23.4%) had secondary
      MIBC (study group 2 [SG2]). Patients in SG2 were stratified into risk groups
      according to the results of the first and last TURBT in non-MIBC using the EORTC
      progression score. RESULTS: CSM for patients with primary and secondary MIBC did
      not differ significantly. Patients in SG2 with the highest risk for tumor stage
      progression at time of the first and last TURBT in non-MIBC showed a
      significantly higher CSM after RC compared with patients with low-to-intermediate
      risk and compared with patients in SG1. In multivariable analyses, stage pT 3/4
      (hazard ratio [HR], 2.12; P < .001), lymphovascular invasion (LVI) (HR, 3.47; P <
      .001), female sex (HR, 1.35; P = .048), and time from diagnosis of MIBC to RC >
      90 days (HR, 2.07; P < .001) were significantly associated with higher CSM.
      CONCLUSION: Risk stratification by the EORTC progression score can help to
      identify those patients with the highest risk of CSM after progression to MIBC
      and thus enable us to offer these patients a multimodal treatment. Our results
      need to be verified in large prospective studies.

PMID- 24331577
TI  - [11C]choline PET/CT impacts treatment decision making in patients with prostate
      cancer referred for radiotherapy.
AB  - BACKGROUND: The purpose of our study was to analyze the role of [(11)C]choline
      positron emission tomography/computed tomography (cho-PET/CT) in the management
      of patients with prostate cancer referred for radiotherapy. PATIENTS AND METHODS:
      Inclusion criteria for this retrospective study were (1) presence of prostate
      cancer, (2) referral for first radiotherapy course (for primary or recurrent
      tumor) between February 2007 and July 2010, and (3) performance of cho-PET/CT.
      All cho-PET/CT scans were classified according to whether they were positive in
      the prostate/prostate bed (T), pelvic lymph nodes (N), and distant metastases (M)
      or negative. Therapeutic strategy based on the cho-PET/CT evaluation was compared
      with the strategy that would have been proposed had cho-PET/CT imaging not been
      available, following international and national prostate cancer guidelines.
      RESULTS: Eighty-two cho-PET/CT scans performed in 74 patients were analyzed. Cho
      PET/CT was positive in 49 studies (60%): T only in 22 (45% of all positive
      studies); N only in 4 (8%); T in combination with N in 3 (6%); and M in
      combination with T or N, or both, in 16 (33%). Treatment after positive cho
      PET/CT examination included radiotherapy +/- androgen deprivation (29 patients),
      surgery +/- radiotherapy (6 patients), androgen deprivation only (8 patients),
      and other treatment (6 patients). In 22 cases, cho-PET/CT (27%) altered the
      treatment approach compared with the treatment that would have been adopted in
      the absence of cho-PET/CT analysis. CONCLUSION: Cho-PET/CT is valuable in
      defining the extent of disease and supporting therapeutic decisions in the
      management of prostate cancer. The therapeutic strategy turned out to be
      influenced by cho-PET/CT imaging in about one third of the patients included in
      this study.

PMID- 24331578
TI  - Does drug accumulation in bone explain the efficacy and toxicity of docetaxel in
      prostate cancer?

PMID- 24331579
TI  - Clinically localized renal cell carcinoma: which is the best treatment strategy?

PMID- 24331580
TI  - Basilar artery aneurysm presenting with hemiparkinsonism.

PMID- 24331581
TI  - Molecular approaches to differentiate three species of Nematodirus in sheep and
      goats from China based on internal transcribed spacer rDNA sequences.
AB  - Internal transcribed spacer (ITS) rDNA sequences of three Nematodirus species
      from naturally infected goats or sheep in two endemic provinces of China were
      analysed to establish an effective molecular approach to differentiate
      Nematodirus species in small ruminants. The respective intra-specific genetic
      variations in ITS1 and ITS2 rDNA regions were 0.3-1.8% and 0-0.4% in N.
      spathiger, 0-6.5% and 0-5.4% in N. helvetianus, and 0-4.4% and 0-6.1% in N.
      oiratianus from China. The respective intra-specific variations of ITS1 and ITS2
      were 1.8-4.4% and 1.6-6.1% between N. oiratianus isolates from China and Iran,
      5.7-7.1% and 6.3-8.3% between N. helvetianus samples from China and America. For
      N. spathiger, compared with samples from China, sequence differences in ITS1 rDNA
      were 0.3-2.4% in isolates from America, 0.3-2.9% in New Zealand and 2.1-2.4% in
      Australia. Genetic variations in ITS2 rDNA of N. spathiger were 0-0.4% between
      samples from China and America, and 0-0.8% between samples from China and New
      Zealand. Using mutation sites, polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) and specific PCR techniques were developed to
      differentiate these three Nematodirus species. The specific PCR assay allowed the
      accurate identification of N. oiratianus from other common nematodes with a
      sensitivity of 0.69 pg and further examination of Nematodirus samples
      demonstrated the reliability of these two molecular methods. 

PMID- 24331582
TI  - Basic numerical processes in very preterm children: a critical transition from
      preschool to school age.
AB  - BACKGROUND: Serious difficulties in formal mathematical skills have been
      identified in preterm children. By contrast, basic-level numerical skills like
      magnitude judgments have not yet been tested in these children. AIMS: The aim of
      the present research was to investigate whether preterm birth also affects these
      basic numerical abilities, with particular attention to the transition from
      preschool to formal education. METHOD: One hundred-forty very preterm children
      and 60 age-matched controls were recruited in a cross-sectional study at 6 and
      8years of age. Magnitude comparison tasks with non-symbolic dot displays or
      symbolic Arabic-number stimuli, measuring accuracy and reaction time, were
      administered to participants. We also investigated explicit number knowledge, as
      well as general cognitive developmental levels, to gain a broader picture of
      preterm abilities. RESULTS: Despite no general cognitive delay, the more simple
      approximate non-symbolic representation of numerical magnitude was affected by
      preterm birth, with slower reaction times at both ages compared to controls.
      Additionally, clear difficulties in the construction of the symbolic
      representation of numerical magnitude and in explicit number knowledge emerged in
      the 6-year-old preterm children, with a recovery from this serious delay finally
      by 8years. CONCLUSIONS: The serious delays identified here in basic numerical
      abilities in preterm children, despite normal IQ, point to the need for further
      studies in order to elucidate the relationship between basic numerical abilities
      and subsequent difficulties in formal mathematic achievement at school.

PMID- 24331583
TI  - The frequency of heparin-induced thrombocytopenia in Taiwanese patients
      undergoing cardiopulmonary bypass surgery.
AB  - BACKGROUND/PURPOSE: There are few studies on heparin-induced thrombocytopenia
      (HIT) reported from Taiwan and Asian countries. We conducted a prospective study
      to investigate the frequency of HIT in patients undergoing cardiopulmonary bypass
      surgeries. METHODS: A cohort of 54 patients was enrolled from January 01, 2010 to
      October 31, 2011. Patients' clinical information was obtained for 4T score
      classification. Plasma (2-4 mL) was also collected before surgery and on Days 5
      and 10 following heparin administration during the bypass procedure. This was
      tested for anti-heparin/PF4 antibodies and functional assay using flow cytometry
      (FC). RESULTS: The mean platelet count for this cohort followed the expected
      pattern in the postoperative setting. Seven of the 54 (13%) patients had positive
      antibodies assays before bypass surgery. This increased to 32% on Day 5 and was
      markedly elevated to 63% on Day 10 after surgery. Only one of the 54 patients
      (1.8%) was found to have both positive antibody assay and platelet activation,
      but no clinical HIT/thrombosis developed. CONCLUSION: Our study is the first
      report on the rates of HIT in the setting of cardiopulmonary bypass surgery in
      Taiwan and demonstrated no clinical HIT occurrence, despite the high frequency of
      HIT antibody in our cohort.

PMID- 24331584
TI  - The Diaphanous-related formin dDia1 is required for highly directional phototaxis
      and formation of properly sized fruiting bodies in Dictyostelium.
AB  - Diaphanous-related formins (DRFs) act as downstream effectors of Rho family
      GTPases and drive the formation and elongation of linear actin filaments in
      various cellular processes. Here we analyzed the DRF dDia1 from Dictyostelium
      cells. The biochemical characterization of recombinant dDia1-FH1FH2 by bulk
      polymerization assays and single filament TIRF microscopy revealed that dDia1 is
      a rather weak nucleator. Addition of any of the three Dictyostelium profilin
      isoforms, however, markedly accelerated formin-mediated actin filament barbed end
      elongation in TIRF assays. Interestingly, filament elongation was significantly
      faster in presence of DdPFN I (profilin I) when compared to the other two
      isoforms, suggesting selectivity of dDia1 for DdPFN I. Additionally, we
      frequently observed dissociation of the formin from growing barbed ends. These
      findings are consistent with dilution-induced depolymerization assays in presence
      of dDia1-FH1FH2 showing that dDia1 is a weak capper in comparison with
      heterodimeric capping protein. To study the physiological role of this formin, we
      created cell lines lacking dDia1 or overexpressing GFP-tagged dDia1. Of note,
      constitutively active dDia1 accumulated homogenously in the entire pseudopod
      suggesting that it controls microfilament architecture to regulate cell
      migration. Comparison of wild type and dDia1-null cells in random cell migration
      and chemotaxis toward a cAMP gradient revealed no major differences. By contrast,
      phototaxis of dDia1-deficient cells during the multicellular stage was markedly
      impaired. While wild type slugs moved with high directionality toward the light
      source, the trails of dDia1-null slugs displayed a characteristic V-shaped
      profile and deviated in angles between 50 degrees  and 60 degrees  from the path
      of the incident light. Possibly in conjunction with this defect, dDia1-null cells
      also formed substantially smaller fruiting bodies. These findings demonstrate
      dDia1 to be critically involved in collective cell migration during terminal
      differentiation. 

PMID- 24331585
TI  - Clinical factors associated with postictal headache in Chinese patients with
      partial epilepsy.
AB  - PURPOSE: To investigate the incidence of postictal headache (PIH) and the factors
      potentially related to the occurrence of PIH in a Chinese epileptic center.
      METHODS: Consecutive adult patients with epilepsy, referred to the outpatient
      clinic of the Epilepsy Center of the PLA General Hospital between February 01,
      2012, and May 10, 2013, were recruited to this study. 854 patients with partial
      epilepsy completed a questionnaire regarding headache, 466 patients with temporal
      lobe epilepsy (TLE), 82 patients with occipital lobe epilepsy (OLE) and 306
      patients with frontal lobe epilepsy (FLE). A semi-structured interview was
      performed in those who confirmed headache. RESULTS: PIH occurred in 328 (38.41%)
      of the subjects. By type of epilepsy, PIH was found in 164 (35.19%) of the
      patients with TLE, 46 (56.01%) of the patients with OLE, and 118 (38.56%) of the
      patients with FLE. The incidence of PIH in OLE was significantly higher than in
      TLE and FLE (P<0.05). It occurs more frequently after generalized tonic-clonic
      seizures than other seizure types. Logistic regression analysis revealed that age
      at onset, type of seizure and classification of epilepsy were each significantly
      related to the occurrence of PIH. CONCLUSION: The results of our study revealed
      possible relationships between PIH and the region of epileptic focus and area of
      spread of epileptic discharges.

PMID- 24331586
TI  - Ghrelin as a starvation signal.
AB  - SUMMARY: Ghrelin, a gastrointestinal hormone, functions as an endogenous ligand
      for the growth hormone secretagogue receptor (GHS-R). It comprises 28 amino
      acids, of which the Ser-3 residue is post-translationally modified by the
      addition of octanoyl acid. Ghrelin stimulates feeding and the secretion of growth
      hormone; it is also thought to function in energy conservation. Here, we provide
      an overview of the discovery of ghrelin, its pathophysiological significance, and
      the mechanism of ghrelin-induced feeding.:

PMID- 24331587
TI  - Body adipose distribution among patients with type 2 diabetes mellitus.
AB  - SUMMARY: Both diabetes mellitus (DM) and obesity are prevalent in adults. The
      relationship between DM and body adipose tissue (AT) distribution is complex and
      although it has been investigated extensively, the subject remains controversial.
      Although a causal association between DM and obesity and AT distribution cannot
      be established on the basis of existing data, it is possible to conclude from
      many studies that gene, serum sex steroids level, daily physical activity and
      food supply can be the risk of obesity and AT redistribution factor among type 2
      DM patients (T2DM). Obesity and AT redistribution of T2DM patients can increase
      the risk of insulin resistant (IR), cardiovascular disease and many other
      disorders. Even though obesity and AT redistribution screening or prophylactic
      treatment in all patients with T2DM is not being recommended at present, such
      patient populations should be given general guidelines regarding exercise, food
      intake control, and even medicinal treatment. The extent of diagnostic and
      therapeutic interventions should be based on the individual's risk profile.:

PMID- 24331588
TI  - Effects of octreotide on nitric oxide synthase expression in the small intestine
      of high fat diet-induced obese rats.
AB  - SUMMARY:  OBJECTIVE: To investigate whether obesity induced by high fat diet is
      associated with expression of neuronal, endothelial, and inducible nitric oxide
      synthase (nNOS, eNOS, and iNOS) in the intestine, and to test the effects of the
      somatostatin analog octreotide on this expression. METHODS: The study included
      high fat diet-induced obese and normal control rats. The obese rats were further
      separated into an obese control group and an octreotide intervention group. Rats
      in the intervention group were injected with 40 MUg/kg octreotide every 12 h for
      8 days. Expressions of nNOS, eNOS, and iNOS in the small intestine were analyzed
      by RT-PCR and immunohistochemistry. The NO level of small intestinal homogenate
      was measured with an ELISA kit. RESULTS: The body weight; Lee's index; small
      intestinal eNOS and iNOS mRNA and protein expression levels; nNOS protein
      expression levels; and small intestinal homogenate NO levels were all
      significantly higher in the obese control group than in the normal controls (p <
      0.01); nNOS mRNA expression was also higher in the obese control group, but not
      significantly so. Octreotide intervention significantly reduced the body weight
      and small intestinal homogenate NO level of the obese rats relative to the obese
      control group (p < 0.05). The mRNA and protein expression levels of eNOS and
      iNOS; the protein expression level of nNOS in the small intestine were also
      significantly lower in the octreotide intervention group than in the obese
      control group (p < 0.01), while nNOS mRNA expression was lower but not
      significantly so. CONCLUSION: High fat diet-induced obesity is associated with
      elevated small intestinal nNOS, eNOS, and iNOS expression levels. Octreotide
      treatment can inhibit nNOS, eNOS, and iNOS expression and lead to weight loss.

PMID- 24331589
TI  - Angiotensin receptor 1 blocker valsartan normalizes gene expression profiles of
      3T3-L1 adipocytes altered by co-culture with LPS-treated RAW264.7 macrophages.
AB  - SUMMARY: Macrophages in adipose tissue reportedly play a major role in the
      development of insulin resistance and chronic inflammation associated with
      obesity. On the other hand, several clinical trials have revealed angiotensin II
      receptor blockers (ARBs) to improve insulin resistance. In this study, we
      analyzed the gene expression profile of 3T3-L1 adipocytes co-cultured with LPS
      treated RAW264.7 macrophages in the presence or the absence of the angiotensin
      receptor 1 blocker valsartan, for 4, 8, 12 and 24 h. The genes of which
      expressions were affected by LPS-treated RAW macrophages but normalized by co
      addition of valsartan were analyzed using KeyMolnet Lite. They included many NF
      kappaB, thyroid receptor and AP-1 target transcripts. In addition, the expression
      patterns of caspases, integrins, matrix metallopeptidases and adipogenic genes,
      altered by co-culture with LPS-treated RAW cells, were generally normalized by
      valsartan treatment. In light of these data, it is reasonable to consider
      valsartan to normalize altered gene expression patterns in adipose tissue
      infiltrated by macrophages, and to ameliorate inflammation, apoptosis and
      fibrotic changes of adipose tissue. Although there may be multiple mechanisms by
      which ARBs ameliorate insulin resistance, for example, through effects on muscle
      or other tissues via the circulatory system, this is the first report
      demonstrating that a favorable effect of valsartan involves normalization of the
      interaction between adipocytes and macrophages. This mechanism of valsartan
      action holds promise for developing treatments for obesity-related insulin
      resistance.:

PMID- 24331590
TI  - A 12-month, randomised, controlled trial to examine the efficacy of the Korean
      diet in an Australian overweight and obese population - A follow up analysis.
AB  - SUMMARY:  BACKGROUND: The prevalence of obesity is remarkably low in South Korea
      in comparison to other countries of similar economic development, which may be in
      part due to traditional diet. Previously we demonstrated that such a traditional
      Korean diet (KD) resulted in similar weight loss to a Western diet (WD) in an
      Australian population despite a higher energy intake by the KD group. However,
      food acceptability scores significantly favoured the WD, suggesting that the KD
      was less enjoyable to this Western population. METHODS: A follow-up study was
      conducted at 6, 9 and 12 months to assess whether the KD group were successful in
      maintaining anthropometric measures, to establish the longer term food
      acceptability of the KD, and to assess for the significance of predictors on body
      weight change. RESULTS: There was some increase in anthropometric measures during
      the follow-up period. Food acceptability scores increased for the KD group when
      no longer being provided with daily meals. The regular intake of Korean food was
      found to be correlated to body weight change, with a more frequent intake of
      Korean food associated with greater weight loss (r = -0.31, p = 0.04).
      CONCLUSIONS: The continual intake of Korean food was a predictor of weight loss
      and therefore it may serve an important role in weight maintenance and should be
      incorporated into future trials. If these findings are confirmed in prospective
      studies they may have important implications in understanding how to minimise
      weight promoting counter-regulatory changes that develop following weight loss.

PMID- 24331591
TI  - Both eating till feeling full and rapid eating are associated with clustering of
      psychosomatic problems and preference for strong tastes.
AB  - SUMMARY:  BACKGROUND: Both eating till feeling full and eating rapidly may
      increase metabolic risk factors including obesity. The associations of such
      habits with psychosomatic problems and preference for strong tastes require
      further exploration. METHODS: The associations between various eating behaviors
      and 12 psychosomatic problems (mental burden, sleep disorder, tendency to
      palpitation, diarrhea, pessimism, amnesia, anger, poor personal relationship,
      fatigue, epigastric distress, shoulder stiffness, and lumbago), and preference
      for strong tastes were compared in 8240 men and 2955 women who underwent routine
      health examinations. The subjects were divided into four groups defined by
      subjective reporting - G1: not eating till feeling full and not eating rapidly;
      G2: eating till feeling full only; G3: eating rapidly only; G4: eating both
      rapidly and till feeling full. RESULTS: Compared to G1, the age-adjusted odds
      ratios were significantly higher in G2-G4 for mental burden [1.17 (1.01-1.35),
      1.26 (1.14-1.41), 1.50 (1.31-1.73) in men; and 1.28 (1.003-1.62), 1.50 (1.21
      1.85), 1.94 (1.50-2.51) in women], and for 8, 8, 11 items in men and 9, 6, 11
      items in women among 11 psychosomatic problems other than mental burden, and for
      preference for strong tastes [2.25 (1.91-2.64), 1.89 (1.67-2.14), 3.36 (2.89
      3.91) in men; and 3.26 (2.34-4.51), 2.88 (2.10-3.93), 5.59 (4.02-7.78) in women].
      CONCLUSIONS: Both eating till feeling full and eating rapidly are associated with
      mental burden, clustering of psychosomatic problems and a preference for strong
      tastes. Mental consultation and attention to choosing mild tasting foods may
      alleviate such eating behaviors and improve health.

PMID- 24331592
TI  - Waist circumference is a better predictor than body mass index of insulin
      resistance in type 2 diabetes.
AB  - Summay: BACKGROUND: Insulin resistance is an important pathogenic factor in type
      2 diabetes patents. An easy and efficiency measurement predicting insulin
      resistance; which can be done easily by type 2 patients is desired. OBJECTIVE: To
      examine whether waist circumference is a better predictor of insulin resistance
      in type 2 diabetes than body mass index (BMI). METHODS: From a population of 1356
      registered diabetic patients, 144 who met (1) aged between 30 and 75 years, (2)
      being Chinese, (3) having had type 2 diabetes for more than one year, and (4)
      having been taking gliclazide and metformin for more than 6 months were enrolled
      in this study. The main outcome evaluated is the associations of HOMA insulin
      resistance index (HOMA index); which were assessed using multiple linear
      regression analysis. RESULTS: The coefficients of multiple regression analysis
      with stepwise model showed that waist circumference (beta = 0.35, p < 0.001) but
      not BMI (beta = 0.01, p = 0.94), adiponectin (beta = -0.25, p = 0.04) and
      hemoglobulin A1c% (HbA1c) (beta = 0.25, p = 0.01) were the main predictors of
      HOMA index. CONCLUSIONS: These initial findings indicate that waist circumference
      is a better predictor of insulin resistance in type 2 diabetes than BMI.

PMID- 24331594
TI  - Predictors of retention and BMI loss or stabilization in obese youth enrolled in
      a weight loss intervention.
AB  - SUMMARY:  OBJECTIVE: To evaluate predictors for intervention dropout and
      successful reduction of metabolic syndrome risk factors among obese children
      enrolled in a short-term, clinic-based weight-loss intervention. DESIGN, SETTING,
      SUBJECTS: Retrospective database review of 1080 children 8 months to 17 years.
      seen a pediatric obesity clinic. INTERVENTIONS: Behavior modification counseling
      to induce change in dietary and exercise choices. MAIN OUTCOME MEASURES: (1) Pre
      /post-intervention change in body mass index (BMI), waist circumference, blood
      pressure, glucose, insulin, and cholesterol (LDL, HDL, & total). (2) Predictors
      of successful decrease in BMI and clinic drop-out. ANALYSIS: Paired t-tests for
      pre-/post-intervention comparisons. Linear regression to assess predictors of
      success and predictors of drop-out, with adjustment for age, gender, race,
      insurance status, and service area. RESULTS: Among children evaluated, adolescent
      females were most likely to achieve successful decrease in BMI, insulin level,
      and LDL cholesterol post-intervention. Nearly 40% of children dropped out early
      in the intervention. Predictors of drop out included age <6 years, public
      insurance status, follow-up scheduled during summer months, and residence in a
      tertiary service area. CONCLUSIONS: Clinic-based weight loss interventions can
      lead to successful improvements in BMI and other metabolic parameters in
      pediatric populations and may be more likely among adolescent females than in
      younger children or males. Drop-out is common, particularly among younger
      children, children with public insurance and children scheduled for follow-up in
      the summer. Identification of these drop-out predictors in individual patients
      may help in targeting children likely to succeed in short-term, clinic-based,
      weight-loss interventions.

PMID- 24331593
TI  - Intracellular lipid content of liver and skeletal muscle in patients with adult
      growth hormone deficiency without diabetes mellitus.
AB  - SUMMARY:  BACKGROUND: Insulin resistance (IR) and visceral obesity are often
      observed in adult growth hormone deficiency patients (AGHDs). However, there is
      little information regarding the intrahepatic lipid (IHL) or the intramyocellular
      lipid (IMCL) content and their association with IR in AGHDs. The aim of this
      study was to directly assess IHL and IMCL in AGHDs by proton magnetic resonance
      spectroscopy and to evaluate the association of lipid levels with IR. METHODS:
      Appropriate hormone replacement therapy (RT) other than GH and estrogen was
      prescribed before evaluation. Ten AGHDs (aged 23-75 years) without diabetes or
      elevation of aminotransferases were examined the percent body fat, visceral fat
      area (VFA), IHL, IMCL, adipokines and glucose metabolism. In two AGHDs, changes
      of these parameters were evaluated after GHRT. RESULTS: Visceral obesity and
      metabolic syndrome was found in 100% and in 80% of the patients, respectively.
      IHL was significantly higher than that in non-obese healthy controls (12.5 +/-
      4.6 vs. 0.69 +/- 0.46%, M +/- SE, p = 0.0330), while IMCL did not differ between
      AGHDs and controls (528.8 +/- 137.2 vs. 378 +/- 51.1 mM, p = 0.2728). Homeostasis
      model assessment of IR was significantly correlated with IHL (r = 0.896, p =
      0.0001) and IMCL (r = 0.749, p = 0.0102), but not with the VFA or percent truncal
      fat mass. A decrease of IHL and improvement of glucose tolerance were observed in
      the two patients after 6 M GHRT. CONCLUSION: These results demonstrated that IHL,
      but not IMCL, may increase in AGHDs, and that IHL may associate with IR. GHRT may
      decrease IHL along with amelioration of IR.

PMID- 24331595
TI  - Value of dual-energy X-ray absorptiometry derived parameters vs anthropometric
      obesity indices in the assessment of early atherosclerosis in abdominally obese
      men.
AB  - SUMMARY:  OBJECTIVE: The purpose of this study was to evaluate the value of dual
      energy X-ray absorptiometry (DEXA) derived parameters vs anthropometric obesity
      indices in the assessment of early atherosclerosis in abdominally obese men.
      METHODS: This case-control study included 44 abdominally obese men (waist
      circumference >= 90 cm) and 30 non-abdominally obese men (waist circumference <
      90 cm) who were between 20 and 50 years of age. All subjects were of the Han
      ethnicity. The carotid intima-media thickness (CIMT) was used as a surrogate
      marker of early atherosclerosis. In the first multiple linear regression model,
      body fat distribution was assessed by anthropometric obesity indices, while in
      the second one it was quantified by DEXA-derived parameters. RESULTS: CIMT (0.74
      +/- 0.11 vs 0.67 +/- 0.04 mm) were significantly higher in the abdominally obese
      men than in the non-abdominally obese men (P < 0.01). CIMT was positively
      correlated with anthropometric obesity indices (r: 0.352-0.488, P < 0.01) and the
      indices from DEXA(r: 0.244-0.482, P < 0.05). The correlation coefficients of
      anthropometric obesity indices and the indices from DEXA were highest for waist
      to height ratio and trunk fat mass, respectively. In model 1, 23.8% of the total
      variance of CIMT was due to waist to height ratio. In model 2, trunk fat mass
      explained 23.2% of the total variance of CIMT. CONCLUSIONS: The present study
      demonstrates the importance of characterizing body fat distribution in
      identifying early atherosclerosis. Body fat distribution evaluated by dualenergy
      X-ray absorptiometry was associated with CIMT, but was not superior to
      anthropometric measurements.

PMID- 24331596
TI  - The distribution, relative abundance, and seasonal phenology of Ceratitis
      capitata, Ceratitis rosa, and Ceratitis cosyra (Diptera: Tephritidae) in South
      Africa.
AB  - Ceratitis capitata (Wiedemann), Ceratitis rosa Karsch, and Ceratitis cosyra
      (Walker) are fruit fly species (Diptera: Tephritidae) of economic importance in
      South Africa. These pests cause direct damage to a number of commercially
      produced fruit and are of phytosanitary concern. A study was conducted to
      determine the distribution, relative abundance, and seasonal occurrence of the
      three species in different climatic regions of South Africa. The relative
      abundance and seasonal phenology of C. capitata and C. rosa were also compared
      between production areas and home gardens in Stellenbosch, Western Cape. Yellow
      bucket traps baited with Biolure were used to trap the flies over a 2-yr period
      in the different sampling areas. Different fruit types were sampled in
      Stellenbosch to determine fruit fly infestation. C. capitata was found to have a
      widespread distribution in South Africa, whereas C. rosa were absent from or only
      present in low numbers in the drier regions. C. cosyra was restricted to the
      North East and East coast, following a similar pattern to the distribution of
      marula, Sclerocarrya birrea, an important wild host. Fruit in home gardens
      provided a breeding ground for C. capitata and C. rosa and a source for
      infestation of orchards when fruit started to mature, highlighting the need for
      an area-wide strategy for the control of fruit flies. 

PMID- 24331597
TI  - Arthropod communities on native and nonnative early successional plants.
AB  - Early successional ruderal plants in North America include numerous native and
      nonnative species, and both are abundant in disturbed areas. The increasing
      presence of nonnative plants may negatively impact a critical component of food
      web function if these species support fewer or a less diverse arthropod fauna
      than the native plant species that they displace. We compared arthropod
      communities on six species of common early successional native plants and six
      species of nonnative plants, planted in replicated native and nonnative plots in
      a farm field. Samples were taken twice each year for 2 yr. In most arthropod
      samples, total biomass and abundance were substantially higher on the native
      plants than on the nonnative plants. Native plants produced as much as five times
      more total arthropod biomass and up to seven times more species per 100 g of dry
      leaf biomass than nonnative plants. Both herbivores and natural enemies
      (predators and parasitoids) predominated on native plants when analyzed
      separately. In addition, species richness was about three times greater on native
      than on nonnative plants, with 83 species of insects collected exclusively from
      native plants, and only eight species present only on nonnatives. These results
      support a growing body of evidence suggesting that nonnative plants support fewer
      arthropods than native plants, and therefore contribute to reduced food resources
      for higher trophic levels. 

PMID- 24331598
TI  - How firebrats (Thysanura: Lepismatidae) detect and nutritionally benefit from
      their microbial symbionts Enterobacter cloacae and Mycotypha microspora.
AB  - The phylogenetically ancient firebrats, Thermobia domestica (Packard) (Thysanura:
      Lepismatidae), lack any form of long-distance communication, yet are able to
      locate mates in sustained hot and humid microhabitats, typically within human
      habitations where they feed on dried goods, including cellulosic substrates. We
      have recently shown that firebrats aggregate in response to two symbiotic
      microorganisms in their feces, the bacterium Enterobacter cloacae and the fungus
      Mycotypha microspora. Our objectives were to determine how firebrats detect M.
      microspora and E. cloacae, and whether these microbial symbionts nutritionally
      benefit firebrats. Applied to a glass surface in bioassays, E. cloacae as well as
      the isolated exopolysaccharide of E. cloacae induced arrestment of firebrats,
      whereas M. microspora induced arrestment only in the presence of cellulosic
      substrate. When M. microspora and E. cloacae were grown aerobically on cellulose
      agar, only M. microspora yielded zones of clearing indicative of enzymatic
      cellulose degradation. Firebrats also arrested in response to d-glucose, which is
      a constituent of the exopolysaccharide and which is produced by the cellulase of
      M. microspora during cellulose degradation. First- to third-instar nymphs of
      firebrats that were fed E. cloacae, M. microspora, or a nutrient-rich diet
      developed equally well. By consuming E. cloacae and M. microspora, and by
      spreading them through feces, firebrats appear able to occupy nutrient-poor
      habitats that otherwise would not support development of their offspring. 

PMID- 24331599
TI  - Low-level detection of candidatus Liberibacter solanacearum in Bactericera
      cockerelli (Hemiptera: Triozidae) by 16s rRNA Pyrosequencing.
AB  - Accurate detection and quantification of Candidatus Liberibacter solanacearum
      (CLs), the putative causal agent of zebra chip disease of potato (Solanum
      tuberosum L.), in the potato psyllid, Bactericera cockerelli (Sulc), has become
      necessary to better understand the biology of the disease cycle. Studies on the
      transmission efficiency of potato psyllids have shown inconsistencies with field
      surveys. There have also been reports of laboratory colonies inexplicably losing
      and regaining CLs infection as detected by polymerase chain reaction (PCR). Until
      now, DNA primers were used to detect CLs in potato psyllid tissue using
      conventional polymerase chain reaction (PCR) and gel electrophoresis or by real
      time quantitative PCR. In this study, CLs was detected using bacterial tag
      encoded FLX amplicon pyrosequencing (bTEFAP) at levels identifiable by PCR, and
      low levels, including samples with only one cell of CLs. Potato psyllids with
      <300 pyrosequencing reads did not show positive using conventional PCR. These
      results indicate that the currently accepted PCR diagnostic technique produces
      false negatives due to detection limits higher than what is generally present in
      field collected psyllids, and also provides an explanation as to why laboratory
      colonies seem to lose and regain CLs infection. 

PMID- 24331600
TI  - Isolation and characterization of bacteria from midgut of the rice water weevil
      (Coleoptera: Curculionidae).
AB  - Gut bacteria are known to play important and often essential roles in the biology
      of insects. Theoretically, they can be genetically manipulated, then reintroduced
      into insects to negatively modify specific biological features. The weevil
      superfamily Curculionoidea is one of the most species-rich and successful animal
      groups on earth, but currently the overall knowledge of the bacterial communities
      in weevils and their associations with hosts is still limited. In this study, we
      isolated and characterized the bacteria in the midgut of an invasive weevil,
      Lissorhoptrus oryzophilus Kuschel, by culturing methods. Female adults of this
      weevil were collected from four different geographic regions of the United States
      and mainland China. Sequencing of the bacterial 16S rRNA amplicons demonstrated
      that the major culturable gut bacteria of rice water weevil are gamma
      proteobacteria and Bacilli. The gut bacterial composition differs among regions,
      with many of the bacteria isolated from only a single region while several were
      detected from more than one region. Overall, the diversity of gut bacteria in
      rice water weevil is relatively low. The possible origins of certain bacteria are
      discussed in relation to the weevil, rice plant, and bacteria. 

PMID- 24331601
TI  - Symbiont diversity in Reticulitermes santonensis (Isoptera: Rhinotermitidae):
      investigation strategy through proteomics.
AB  - The complex microbial community living in the hindgut of lower termites includes
      prokaryotes, flagellates, yeasts, and filamentous fungi. Many microorganisms are
      found in the termite gut, but only a few are thought to be involved in symbiotic
      association to participate in cellulose digestion. Proteomics provides analyses
      from both taxonomical and functional perspectives. We aimed to identify symbiont
      diversity in the gut of Reticulitermes santonensis (Feytaud), via complementary
      electrospray ionization associated to ion trap tandem mass spectrometry (LC
      MS/MS) and two-dimensional gel electrophoresis associated to matrix-assisted
      laser desorption-ionization-time-of-flight mass spectrometry analysis. One
      specific challenge to the study of lower termites is the relatively few data
      available on abundant symbiotic flagellates. Analysis based on LC-MS/MS revealed
      few protein families showing assignments to eukaryotes and the taxonomic origin
      of highly represented actins could not be established. Tubulins proved to be the
      most suitable protein family with which to identify flagellate populations from
      hindgut samples using LC-MS/MS, compared with other protein families, although
      this method targeted few prokaryotes in our assay. Similarly, two-dimensional gel
      electrophoresis associated to matrix-assisted laser desorption-ionization-time-of
      flight mass spectrometry did not succeed in identifying flagellate populations,
      but did permit the identification of most of the prokaryotic components of the
      symbiotic system. Finally, fungi and yeasts were identified by both methods.
      Owing to the lack of sequenced genes in flagellates, targeting tubulins for LC
      MS/MS could allow fingerprints of flagellate populations to be established.
      Experimental and technical improvements might increase the efficiency of
      identification of prokaryotic populations in the near future, based on
      metaproteomic development. 

PMID- 24331602
TI  - Biology of the introduced biocontrol agent Microctonus hyperodae (Hymenoptera:
      Braconidae) and its host Listronotus bonariensis (Coleoptera: Curculionidae) in
      northern New Zealand.
AB  - The South American weevil Listronotus bonariensis (Kuschel) is an important pest
      of pastures in New Zealand. As a component of management strategies for this
      pest, the South American parasitoid Microctonus hyperodae Loan (Hymenoptera:
      Braconidae) was released in northern New Zealand during 1991 as a biological
      control agent. Over the subsequent 5-6 yr, the reproductive biology of M.
      hyperodae and its relationship to, and effects on, the reproductive phenology and
      fitness of L. bonariensis were studied at three sites. M. hyperodae was first
      recovered in the field in December 1991. Subsequently, the incidence of
      parasitism in L. bonariensis increased to seasonal maxima of 75-90%. There was
      variable synchrony between parasitoid generations and the two generations of its
      host, leading to marked seasonal variation in rates of parasitism and parasitoid
      abundance. Despite marked inter-year variation, abundance of host adult and egg
      populations declined in the presence of parasitoids. Parasitized host females had
      lower ovarian maturity scores, had lower egg loads, and exhibited less investment
      in wing muscle development than females that had escaped parasitism. There was
      almost complete elimination of egg maturation in parasitized females and these
      hosts contributed little to population recruitment. Rate of buildup and seasonal
      maxima in parasitism, frequency of superparasitism, adult abundances, and wing
      muscle development in adult L. bonariensis varied among the three sites in a
      manner that was only partially related to climate differences across the 1.83
      degrees  gradient of latitude. Site effects were weak to absent in measures of
      reproductive condition in L. bonariensis females.

PMID- 24331603
TI  - Hypothenemus hampei (Coleoptera: Curculionidae) and its interactions with Azteca
      instabilis and Pheidole synanthropica (Hymenoptera: Formicidae) in a shade coffee
      agroecosystem.
AB  - The coffee berry borer is currently the most important insect pest of coffee
      worldwide. In shaded coffee farms such as Finca Irlanda in Chiapas, Mexico,
      natural enemies limit coffee berry borer and potentially prevent outbreaks. This
      research aimed to determine the effect of ants on coffee berry borer damage and
      to describe behaviors of Azteca instabilis F. Smith and Pheidole synanthropica
      (Longino 2009) when encountering the coffee berry borer. To these ends, an ant
      survey was conducted in a 2,500-m(2) plot within the farm. A 4- by 4-m coordinate
      system was established, and the coffee plant or shade tree closest to the
      coordinate point was sampled using tuna fish for a total of 168 coffee plants and
      46 shade trees sampled. In addition, up to 100 berries were harvested from 138
      coffee plants to measure damage and verify the presence of the coffee berry
      borer. Behavior was determined in the field by placing live coffee berry borer
      adults on berries and video recording all attacks. Results showed that plants
      with ants had less percentage of damaged berries and shorter coffee berry borer
      galleries than plants without ants. However, the length of galleries in plants
      with A. instabilis showed no significant differences from plants without ants. P.
      synanthropica was observed carrying coffee berry borer to the nest in 50% of the
      cases, whereas A. instabilis threw coffee berry borer off of the coffee plant in
      79% of the cases. Results indicate that the presence of these species of ants
      reduce coffee berry borer damage and suggest that different behaviors could
      explain the pattern of coffee berry borer attack in this agroecosystem. 

PMID- 24331604
TI  - Establishment, population increase, spread, and ecological host range of
      Lophodiplosis trifida (Diptera: Cecidomyiidae), a biological control agent of the
      invasive tree Melaleuca quinquenervia (Myrtales: Myrtaceae).
AB  - The Australian tree Melaleuca quinquenervia (Cavanilles) Blake is an invasive
      weed in wetland systems of Florida. A biological control program targeting M.
      quinquenervia has resulted in the release of the gall forming midge Lophodiplosis
      trifida Gagne (Diptera: Cecidomyiidae). Populations of the introduced herbivore
      readily established at all 24 release sites across the weed's range in Florida,
      and there was no evidence that founding colony size (100, 2,000, or 6,000 adults)
      influenced herbivore establishment or local population growth rates. Landscape
      level spread of L. trifida from release sites averaged nearly 6 km/yr, ranging as
      high as 14.4 km/yr. Prerelease host range testing predicted that L. trifida
      oviposits indiscriminately on test plant species but does not complete
      development on any of the test species, including congeners present in Florida.
      To test the predictability of these host range tests, L. trifida was released in
      a common garden consisting of 18 test plant species that were interplanted with
      M. quinquenervia. Plant species postulated to be at risk experienced no gall
      development by L. trifida while intermingled M. quinquenervia trees supported
      704.8 (+/- 158.5) galls per plant. Historically, many introduced Cecidomyiidae
      have limited effect on plant performance of target weeds because of recruitment
      of native parasitoids that disrupt biological control efficacy. In contrast to
      this trend, there has been no evidence to date that parasitoids are exploiting L.
      trifida in Florida.

PMID- 24331605
TI  - Semiochemicals released by pecan alleviate physiological suppression in
      overwintering larvae of Acrobasis nuxvorella (Lepidoptera: Pyralidae).
AB  - Acrobasis nuxvorella Neunzig (pecan nut casebearer) is a monophagous herbivore of
      Carya illinoinensis (Wang.) K. Koch (pecan); both are indigenous to North
      America, where Carya has evolved for ~60 million years. We hypothesized that this
      close association may have resulted in a parallel evolution allowing casebearer
      to use pecan volatiles to synchronize seasonality. Casebearer overwinters in
      diapause as a first-instar larva in a hibernaculum attached to a dormant pecan
      bud. Larval emergence from this structure after diapause or postdiapause
      quiescence coincides with the onset of pecan bud growth in the spring, and this
      interaction was the subject of this study. Dormant pecan twigs with hibernacula
      infested buds were exposed to a water control or pecan volatiles from 'Western
      Schley' cultivar, and monitored to observe larval response by using a
      microcalorimeter. Initial testing showed that metabolic heat produced by
      overwintering larvae remained low and unchanged when exposed to water vapor and
      significantly increased within a few hours after exposure to volatiles from new
      pecan foliage. This shows that these larvae in hibernacula are in a
      physiologically suppressed state of diapause or postdiapause quiescence, from
      which they detect and respond to these pecan volatiles. Further studies to
      quantify larval responses showed that 90 and 80% of the larvae became active and
      emerged from their hibernacula ~6 d after exposure to Western Schley and
      'Wichita' volatiles, respectively. Mixtures of 13 sesquiterpenes from those pecan
      volatiles were identified to induce physiological activity within larvae after
      hours of exposure, followed some days later by larval emergence from hibernacula.
      Host volatiles, to our knowledge, have not previously been reported to induce
      early instar larvae in hibernacula to rouse from a state of physiological arrest
      to resume normal growth and development. This also has potential for use in pest
      management.

PMID- 24331606
TI  - Infection rates and comparative population dynamics of Peregrinus maidis
      (Hemiptera: Delphacidae) on corn plants with and without symptoms of maize mosaic
      virus (Rhabdoviridae: Nucleorhabdovirus) infection.
AB  - We examined the population dynamics of the corn planthopper Peregrinus maidis
      (Ashmead) (Hemiptera: Delphacidae) throughout a cycle of corn (Zea mays L.)
      production on plants with or without symptoms of maize mosaic virus (MMV)
      (Rhabdoviridae: Nucleorhabdovirus) infection. Our results indicate that the
      timing of MMV plant infection greatly influenced the planthopper's host plant
      colonization patterns. Corn plants that expressed symptoms of MMV infection early
      in the crop cycle (28 d after planting) harbored, on average, 40 and 48% fewer
      planthoppers than plants that expressed symptoms of MMV infection later in the
      crop cycle (49 d after planting) and asymptomatic plants, respectively. We also
      observed a change in the number of brachypterous (short-wing type) and
      macropterous (long-wing type) winged forms produced; plants expressing early
      symptoms of MMV infection harbored, on average, 41 and 47% more of the
      brachypterous form than plants with late infections of MMV and plants with no
      symptoms of MMV, respectively. Furthermore, we determined the rates of MMV
      infected planthoppers relative to their wing morphology (macropterous or
      brachypterous) and gender. MMV infection was 5 and 12% higher in females than in
      males in field and greenhouse experiments, respectively; however, these
      differences were not significantly different. This research provides evidence
      that MMV similarly infects P. maidis planthoppers regardless of the gender and
      wing morphotype. These results also suggest that the timing of symptom
      development greatly affects the population dynamics of the planthopper vector,
      and likely has important consequences for the dynamics of the disease in the
      field.

PMID- 24331607
TI  - Feeding injury to cotton caused by Lygus hesperus (Hemiptera: Miridae) nymphs and
      prereproductive adults.
AB  - Despite numerous studies examining feeding injury to cotton (Gossypium spp.)
      caused by different stages of Lygus hesperus Knight, no consistent trends are
      apparent. One explanation for inconsistencies among previous results is failure
      to account for important sources of biological variation. Because it was only
      recently recognized that feeding behavior and injury differed among adults of
      different physiological ages, this source of variance was not controlled in
      earlier studies of Lygus stage-dependent injury. We incorporated this knowledge
      into video assays and greenhouse experiments to compare feeding behaviors, within
      plant distributions, and injury to cotton plants among L. hesperus nymphs and
      prereproductive adults. Laboratory behavior assays indicated third instars
      exhibited more stylet-probes, but of shorter duration, compared with
      prereproductive adults. Numbers and duration of stylet-probes by fifth instars
      were intermediate to those of third instars and adults. Total time spent stylet
      probing was similar among the insect age-classes. On whole plants, third instars
      tended to reside within the bracts of squares (flower buds) >3 mm in diameter,
      whereas fifth instars and adults tended to frequent the plant terminals. Adults
      were more likely than third or fifth instars to be located off the plants at any
      given observation. Plants exposed to fifth instars exhibited more square
      abscission and retained fewer squares 3-6 mm in diameter than did plants exposed
      to third instars or adults. Our results indicated that fifth instars were more
      injurious to cotton than third instars or prereproductive adults, and that
      differences in feeding injury corresponded with within-plant distributions
      exhibited by different L. hesperus age-classes. 

PMID- 24331608
TI  - Feeding-induced interactions between Nilaparvata lugens and Laodelphax
      striatellus (Hemiptera: Delphacidae): effects on feeding behavior and honeydew
      excretion.
AB  - Using electrical penetration graph, salivary flange, and honeydew measurement,
      this study investigated the effects of feeding-induced intra- and interspecific
      interactions on feeding behavior and honeydew excretion of brown planthopper
      (Nilaparvata lugens) compared with small brown planthopper (Laodelphax
      striatellus). Results showed that many measures of feeding behavior were affected
      by feeding-induced intra- and interspecific interactions on two different rice
      varieties. There were significantly fewer salivary flanges for both brown
      planthopper and small brown planthopper on rice plants with feeding-induced
      conspecific or heterospecific effects than on relevant control plants. In
      contrast, only small brown planthopper on rice plants with feeding-induced
      heterospecific effects had significantly fewer salivary flanges than those with
      feeding-induced conspecific effects. The mean durations of pathway activities per
      insect and mean durations from first probe to first sustained phloem ingestion
      for small brown planthopper were significantly shorter, whereas the mean duration
      per insect of phloem ingestion was significantly longer, on rice plants with
      feeding-induced heterospecific effects than those on relevant control plants, as
      well as rice plants with feeding-induced conspecific effects. Honeydew weights of
      small brown planthopper were significantly increased by the induced
      heterospecific effect. Thus, all results indicated indirect, asymmetrical,
      facilitative effects of induced interspecific interactions on the feeding
      behavior and honeydew weight for small brown planthopper on both varieties. These
      findings are consistent with the previously documented asymmetrical effects on
      performance, with more benefits to small brown planthopper from brown planthopper
      indirectly. The change of nutrient and induced allelochemistry in host plant
      probably underlies these facilitative effects. 

PMID- 24331609
TI  - Impact of Halotydeus destructor on crop seedlings at different plant
      developmental stages and levels of moisture stress.
AB  - Tolerance and compensatory ability after invertebrate damage are important
      components of plant defense and are affected by various endogenous and exogenous
      factors. Here, we examine the impact of feeding damage caused by different
      densities of the redlegged earth mite (Halotydeus destructor Tucker) on the
      performance and recovery of canola and wheat seedlings at different plant
      developmental stages, and when grown under three levels of moisture stress. Both
      canola and wheat were susceptible to feeding damage caused by H. destructor at
      early growth development stages (canola-cotyledon, first and second true leaf
      stage; wheat-GS10 and GS12), but tolerated damage at the later growth stages
      (canola-third true leaf stage; wheat-GS14). Wheat plants compensated completely
      for mite feeding damage, while canola plants showed partial compensation when
      feeding occurred at the cotyledon and first true leaf stages. Canola was
      susceptible to immediate feeding damage from H. destructor under all levels of
      moisture stress and did not compensate for this damage over time when grown in
      the unstressed and moderately stressed treatments. Under severe moisture stress
      conditions, plant performance traits and mite density often showed a nonlinear
      relationship, with growth initially increasing as mite density increased, but
      then decreasing markedly as densities exceeded 30 mites/100 cm(2). Wheat
      seedlings were susceptible to immediate feeding damage when grown in the
      unstressed and severe stress conditions, but were generally able to compensate
      for this damage regardless of moisture conditions. The implications of these
      results for the management of H. destructor are discussed. 

PMID- 24331610
TI  - Dispersal pattern of Paederus fuscipes (Coleoptera: Staphylinidae: Paederinae) in
      relation to environmental factors and the annual rice crop cycle.
AB  - Paederus fuscipes Curtis, a dermatitis linearis causing agent, has received
      increasing attention from the public, as it poses a serious health threat after
      mass dispersal into human-dominated areas. Preventive measures against this
      insect have so far been unsuccessful partly because of limited knowledge about
      its dispersal pattern. In this study, the dispersal activity of P. fuscipes was
      studied at infestation-prone residential buildings in Mainland Penang, Malaysia.
      The dispersal activity of P. fuscipes showed two peaks, that is, from February to
      April and August to October. Overall, there was no statistical significant
      correlation between dispersal and climatic parameters, that is, temperature,
      relative humidity, total rainfall, at all sampling localities. However, dispersal
      was primarily caused by human activities in rice fields, which accounted for >60%
      of the variability in dispersal. Particularly, rice harvesting, including straw
      burning, and cultivation were the major factors triggering P. fuscipes dispersal.
      These activities presumably disrupted the habitat and normal activities of P.
      fuscipes and rendered the rice fields unfavorable refuges. In addition, the
      beetles might also face food shortages after the disturbance of their prey base
      in the crop fields. The current study provides a predictive tool of P. fuscipes
      flight periods to ensure insecticide residual spraying is timed in the
      infestation-prone residential areas before the onset of infestation. 

PMID- 24331611
TI  - Harmonic radar tagging for tracking movement of Nezara viridula (Hemiptera:
      Pentatomidae).
AB  - Harmonic radar tagging was investigated as a method for monitoring the movement
      of the southern green stink bug, Nezara viridula (L.) (Hemiptera: Pentatomidae).
      Because adhesive toxicity and tag weight limit the use of this technology,
      initial efforts focused on selection of the optimal adhesive and design of
      harmonic radar tags to reduce impact on the movement of stink bugs. A design
      consisting of a 6-cm-long 0.10-mm-thick silver-plated copper monopole on the
      anode terminal of a three-contact Schottky barrier diode attached with Gorilla
      super glue provided a compromise between unimpaired movement and tracking range,
      adding an additional 8% to the weight of the stink bug while not significantly (P
      > 0.05) reducing walking or flying mobility in the laboratory. Recovery of tagged
      stink bugs in cotton, Gossypium hirsutum (L.), and fallow fields ranged from 10
      to 75% after 24 h, whereas marked stink bugs were recovered at rates of 0-35% by
      using sweep net or drop cloth sampling. The distance dispersed in the field was
      not impacted (P > 0.05) by crop, tagged status, or gender of the insect. Future
      research should examine possible improvements to the harmonic radar transceiver
      and the wire antenna to decrease encumbrance. 

PMID- 24331612
TI  - A comparison of girdled ash detection trees and baited artificial traps for
      Agrilus planipennis (Coleoptera: Buprestidae) detection.
AB  - Detection of newly established populations of Agrilus planipennis Fairmaire, the
      most destructive forest insect to invade the United States, remains challenging.
      Regulatory agencies currently rely on artificial traps, consisting of baited
      three-sided panels suspended in the canopy of ash (Fraxinus spp.) trees.
      Detection trees represent another survey option. Ash trees are girdled in spring
      to attract ovipositing A. planipennis females then debarked in fall to assess
      larval presence and density. From 2008-2010, systematic grids of detection trees
      and artificial traps were established across a 390-km(2) area for the SLow Ash
      Mortality pilot project. We compared probabilities of detection associated with
      detection trees and artificial traps along varying A. planipennis density proxies
      estimated as distance-weighted averages of larval counts (detection trees) or
      adult captures (traps) within 800 m of each detection tree or trap. Detection
      trees were consistently more likely to be positive, that is, detect A.
      planipennis, than traps in all three years, even when traps were placed in
      canopies of detection trees. Probability of detection with a single detection
      tree was >50% when density proxies for the area were <5 larvae per detection
      tree, while the probability of detection with an artificial trap placed in the
      same area was <35%, even when density proxies exceeded 25 larvae per detection
      tree. At very low densities of <5 larvae per detection tree, using three
      detection trees would increase detection probabilities to 90%, while five
      artificial traps would increase the detection probability only to 40%. 

PMID- 24331613
TI  - Attractive toxic sugar baits: control of mosquitoes with the low-risk active
      ingredient dinotefuran and potential impacts on nontarget organisms in Morocco.
AB  - We evaluated the efficacy of attractive toxic sugar baits (ATSB) in the
      laboratory and field with the low-risk active ingredient dinotefuran against
      mosquito populations. Preliminary laboratory assays indicated that dinotefuran in
      solution with the sugar baits was ingested and resulted in high mortality of
      female Culex quinquefasciatus Say and Aedes aegypti Linnaeus. Field studies
      demonstrated >70% reduction of mosquito populations at 3 wk post-ATSB
      application. Nontarget feeding of seven insect orders-Hymenoptera, Lepidoptera,
      Coleoptera, Diptera, Hemiptera, Orthoptera, and Neuroptera-was evaluated in the
      field after application of attractive sugar baits (ASB) on vegetation by
      dissecting the guts and searching for food dye with a dissecting microscope.
      Nontargets were found stained with ASB 0.9% of the time when the application was
      applied on green nonflowering vegetation. Only two families were significantly
      impacted by the ASB application: Culicidae (mosquitoes) and Chironomidae
      (nonbiting midges) of the order Diptera. Pollinators of the other insect orders
      were not significantly impacted. No mortality was observed in the laboratory
      studies with predatory nontargets, wolf spiders or ground beetles, after feeding
      for 3 d on mosquitoes engorged on ATSB applied to vegetation. Overall, this novel
      control strategy had little impact on nontarget organisms, including pollinators
      and beneficial insects, and was effective at controlling mosquito populations,
      further supporting the development of ATSB for commercial use. 

PMID- 24331614
TI  - A spatial ecology study on the effects of field conditions and crop rotation on
      the incidence of Plectris aliena (Coleoptera: Scarabaeidae) grub damage to
      sweetpotato roots.
AB  - A farmscape study was conducted in commercial sweetpotato (Ipomoea batatas (L.)
      Lam) fields in Columbus County, NC, in 2010 and 2011 to investigate the effects
      of the following field conditions: soil drainage class, soil texture, field size,
      border habitat, land elevation, and the previous year's crop rotation on the
      incidence of damage caused by Plectris aliena Chapman (Coleoptera:Scarabaeidae)
      larval feeding. Soil drainage and crop rotation significantly affected the
      incidence of damage to roots, with well drained soils having a low estimated
      incidence of damaged roots (0.004) compared with all other drainage classes
      (0.009-0.011 incidence of damaged roots). Fields with soybeans [Glycine max (L.)
      Merr] planted the preceding year had the highest incidence of root damage (0.15)
      compared with all other crops. The effects of border habitats, which were
      adjacent to grower fields where roots were sampled, showed that as the location
      of the roots was closer to borders of soybean (planted the year before) or grass
      fields, the chance of damage to roots decreased. Results indicate that growers
      can use crop rotation as a management technique and avoid planting sweetpotatoes
      the year after soybeans to reduce the incidence of P. aliena larval feeding on
      sweetpotato roots. Environmental conditions such as fields with poor drainage and
      certain border habitats may be avoided, or selected, by growers to reduce risk of
      damage to roots by P. aliena.

PMID- 24331615
TI  - Comparison of a synthetic chemical lure and standard fermented baits for trapping
      Drosophila suzukii (Diptera: Drosophilidae).
AB  - We determined the attractiveness of a new chemical lure compared with fermented
      food baits in use for trapping Drosophila suzukii Matsumura, spotted wing
      drosophila (Diptera: Drosophilidae), in Connecticut, New York, and Washington in
      the United States and at Dossenheim in Germany. The chemical lure (SWD lure) and
      food baits were compared in two types of traps: the dome trap and a cup trap.
      Regardless of trap type, numbers of male and female D. suzukii trapped were
      greater with the SWD lure compared with apple cider vinegar (ACV) baits at the
      Washington and New York sites, and were comparable with numbers of D. suzukii
      captured with a wine plus vinegar bait (W + V) at Germany site and a combination
      bait meant to mimic W + V at the Connecticut site. Averaged over both types of
      attractants, the numbers of D. suzukii captured were greater in dome traps than
      in cup traps in New York and Connecticut for both male and female D. suzukii and
      in Washington for male D. suzukii. No such differences were found between trap
      types at the Washington site for female and Germany for male and female D.
      suzukii. Assessments were also made of the number of large (>0.5 cm) and small
      (<0.5 cm) nontarget flies trapped. The SWD lure captured fewer nontarget small
      flies and more large flies compared with ACV bait in New York and fewer nontarget
      small flies compared with W + V in Germany, although no such differences were
      found in Washington for the SWD lure versus ACV bait and in Connecticut for the
      SWD lure versus the combination bait, indicating that these effects are likely
      influenced by the local nontarget insect community active at the time of
      trapping. In New York, Connecticut, and Germany, dome traps caught more nontarget
      flies compared with cup traps. Our results suggest that the four-component SWD
      chemical lure is an effective attractant for D. suzukii and could be used in
      place of fermented food-type baits. 

PMID- 24331616
TI  - Response of Tuta absoluta (Lepidoptera: Gelechiidae) to different pheromone
      emission levels in greenhouse tomato crops.
AB  - The response of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) to different
      emission rates of its pheromone, (3E, 8Z, 11Z)-tetradecatrienyl acetate, was
      measured in two greenhouse trials with traps baited with mesoporous dispensers.
      For this purpose, weekly moth trap catches were correlated with increasing
      pheromone emission levels by multiple regression analysis. Pheromone release
      profiles of the dispensers were obtained by residual pheromone extraction and gas
      chromatography quantification. In the first trial carried out in summer 2010,
      effect of pheromone emission was significant as catches increased linearly with
      pheromone release rates up to the highest studied level of 46.8 MUg/d. A new
      trial was carried out in spring 2011 to measure the effect of the emission factor
      when pheromone release rates were higher. Results demonstrated that trap catches
      and pheromone emission fitted to a quadratic model, with maximum catches obtained
      with a release level of 150.3 MUg/d of (3E, 8Z, 11Z)-tetradecatrienyl acetate.
      This emission value should provide enhanced attraction of T. absoluta and improve
      mass trapping, attract-and-kill, or monitoring techniques under greenhouse
      conditions in the Mediterranean area. 

PMID- 24331617
TI  - The effect of fluctuating temperatures during development on fitness-related
      traits of Scatophaga stercoraria (Diptera: Scathophagidae).
AB  - Development of ectotherms is highly temperature dependent. Studies using variable
      thermal environments can improve ecological relevance of data because organisms
      naturally face day-to-day stochastic temperature fluctuations as well as seasonal
      changes in the amplitude of such daily fluctuations. The objective of this study
      was to investigate if, and to what extent, the use of constant temperatures is
      justified in studies of the model species, yellow dung fly, Scatophaga
      stercoraria (L.). We examined the effect of temperature fluctuation on the
      expression of several life history traits and the effect on subsequent adult
      longevity. We used two fluctuating temperature treatments with the same mean but
      different amplitudes (15/21 degrees C, 12/24 degrees C; 12/12 h), and three
      constant temperature treatments spanning the wide temperature range faced in the
      wild (12, 18, and 24 degrees C). Large temperature fluctuation was mostly
      detrimental (lower juvenile survival, slower growth, smaller body size, and
      longer development), whereas moderate temperature fluctuation usually gave
      responses similar to the constant regime. When developing in fluctuating
      temperatures, adult longevity (no effect), body size (lower), and wing shape
      (narrower wings) deviated from the expectations based on the constant temperature
      reaction norms, presumably because of acclimation responses. Contrary to some
      studies no obvious beneficial effects of moderate temperature fluctuation were
      observed. Instead, yellow dung flies seem to canalize development in the face of
      temperature fluctuation up to a point when detrimental effects become
      unavoidable. The relatively greater effects of extreme constant developmental
      temperatures question their biological relevance in experiments. 

PMID- 24331618
TI  - Life history comparison of two green lacewing species Chrysoperla johnsoni and
      Chrysoperla carnea (Neuroptera: Chrysopidae).
AB  - We investigated the life histories of two green lacewing species, Chrysoperla
      johnsoni Henry, Wells, and Pupedis from western North America, and Chrysoperla
      carnea (Stephens) (Neuroptera: Chrysopidae) from western Europe in the
      laboratory. There were both similarities and differences in their life history
      characteristics. C. johnsoni exhibited a significantly longer developmental time
      for egg, first instar, and pupal stage than C. carnea. C. carnea exhibited a
      significantly shorter egg to adult developmental time than C. johnsoni. Except
      for the pupal stage, the survival of all other life history stages was not
      species-specific. All C. carnea pupae were able to develop into adults, whereas
      only 92% of adult eclosion was observed from C. johnsoni pupae. There was no
      difference in egg to adult survival between the two species. Adult longevity was
      not species- or gender-specific. Sex ratio of emerged adults was ~50% in both
      species. C. johnsoni had a longer preoviposition period than C. carnea, while the
      oviposition period was similar for both species. C. carnea had higher lifetime
      fecundity and fertility than C. johnsoni, as measured by total number of eggs
      laid and production of fertile eggs, respectively. Egg viability did not differ
      between the two species. Intrinsic rates of increase (rm) for C. carnea and C.
      johnsoni were 0.161 and 0.132, respectively. All lacewings used in this
      experiment were laboratory reared under environmental conditions similar to field
      as possible. This is the first available information on the life history
      parameters of C. johnsoni.

PMID- 24331620
TI  - Characterization of microsatellites for population genetic analyses of the fungus
      growing termite Odontotermes formosanus (Isoptera: Termitidae).
AB  - The fungus-growing subterranean termite Odontotermes formosanus Shiraki
      (Isoptera: Termitidae) is a destructive pest in Southeast Asia. To facilitate
      studies on the biology, ecology, and control of O. formosanus, we isolated and
      characterized nine novel microsatellite loci from a mixed partial genomic library
      of O. formosanus and the sympatric Macrotermes barneyi Light enriched for di-,
      tri-, and tetranucleotide repeats. We screened these loci in three populations of
      O. formosanus from China. All loci were polymorphic. Three loci showed
      heterozygote deficit possibly because of the presence of null alleles. The
      remaining six loci with 4-15 alleles per locus and an average observed
      heterozygosity of 0.15-0.60 across populations were used for population genetic
      analysis. Populations from different provinces (Guangdong, Jiangxi, and Hubei)
      were genetically differentiated, but the genetic distance between populations was
      surprisingly small (FST: 0.03-0.08) and the gene flow was considerable (Nem: 3
      8), despite the geographical distance being >300 km. Genetic diversity within
      populations was low (allelic richness: 5.1-6.3) compared with other subterranean
      dwelling termites, but consistent with the diversity in species of the family
      Termitidae. Microsatellite markers developed for O. formosanus will allow further
      studies to examine the phylogeography, population genetic and colony breeding
      structure, dispersal ranges, and size of foraging territories in this and closely
      related species, as well as aid in assessing treatment success. 

PMID- 24331619
TI  - The effect of temperature on survival of Pityophthorus juglandis (Coleoptera:
      Curculionidae).
AB  - The walnut twig beetle (Pityophthorus juglandis Blackman) vectors Geosmithia
      morbida, the causal agent of thousand cankers disease in Juglans, and is
      particularly damaging to Juglans nigra L. (black walnut). Native hosts of P.
      juglandis are distributed in the southwestern United States where winter
      temperatures tend to be higher than those found within the native range of black
      walnut. To better understand temperature effects on survival of P. juglandis, we
      initiated studies to determine: 1) seasonal variations in cold tolerance, as
      measured by the supercooling point (SCP), and 2) upper and lower lethal
      temperatures (LT). In the lower LT study, Xyleborinus saxeseni (Ratzeberg) was
      tested for comparison. Insects were either exposed to increasing or decreasing
      temperatures and then checked for survival. Upper and lower LTs were estimated
      using a logistic model. For the SCP study, data were grouped into seasons.
      Seasonal mean SCPs were highest in summer (-15.4 degrees C) and lowest in fall (
      18.1 degrees C). The upper lethal limit estimations required to kill 99% of the
      population (LT99) for adults and larvae were 52.7 and 48.1 degrees C,
      respectively, and lower limit LT99 estimations for adults and larvae were -18.1
      and -18.7 degrees C, respectively. The lower median LT (LT50) of X. saxeseni was 
      24.7 degrees C. These studies, as well as beetle survival in infested Colorado
      trees where temperatures reached -29 degrees C in February 2011, suggest P.
      juglandis could survive the winter in much of the native range of black walnut,
      but may be limited in trees where temperatures regularly exceed the lower LT. 

PMID- 24331621
TI  - Molecular species identification of cryptic apple and snowberry maggots (Diptera:
      Tephritidae) in western and central Washington.
AB  - In Washington state, identification of the quarantine apple pest Rhagoletis
      pomonella (Walsh) is complicated by the presence of the cryptic species
      Rhagoletis zephyria Snow (Diptera: Tephritidae). Distinguishing the two flies is
      important because there is a zero tolerance policy for R. pomonella in apple
      production for export. Here, we attempt to distinguish the two species by scoring
      R. pomonella and R. zephyria populations from western and south-central
      Washington for a set of 11 nuclear markers, including four single nucleotide
      polymorphisms (SNPs) developed for rapid and inexpensive genotyping using Taqman
      real-time quantitative-polymerase chain reaction. We show that the four SNPs may
      be adequate in most cases for distinguishing whether a fly originated from apple
      or black hawthorn (the two major host plants for R. pomonella representing an
      economic risk) versus snowberry (the major host for R. zephyria, and not a
      commercial threat). However, directional introgression of R. zephyria alleles
      into R. pomonella can complicate the identification of flies of mixed ancestry
      based only on the four SNPs. Moreover, this problem is more acute in the
      sensitive apple-growing regions of central Washington where our results imply
      hybridization is common. Consequently, application of the four SNP quantitative
      polymerase chain reaction assay can immediately assist ongoing apple maggot
      monitoring, while the development of additional genetic markers through next
      generation sequencing would be valuable for increasing confidence in species
      identification and for assessing the threat posed by hybridization as R.
      pomonella further spreads into the more arid apple-growing regions of central
      Washington. 

PMID- 24331622
TI  - Identification and transcriptional profiling of differentially expressed genes
      associated with response to UVA radiation in Drosophila melanogaster (Diptera:
      Drosophilidae).
AB  - Ultraviolet A (UVA) radiation, the major component of solar ultraviolet (UV)
      radiation reaching the earth's surface, leads to negative effects in insects,
      such as oxidative stress, photoreceptor damage, and cell death. To better
      understand the molecular mechanisms of insect response to UVA radiation,
      suppression subtractive hybridization (SSH) and real-time quantitative polymerase
      chain reaction approaches were combined to reveal differential transcript
      expression in Drosophila melanogaster Meigen, 1830 (Diptera: Drosophilidae). In
      this study, two subtractive cDNA libraries were constructed and sequenced,
      obtaining 131 high-quality unique expressed sequence tags (ESTs) that were up- or
      downregulated in D. melanogaster exposed to UVA radiation for 0.5 h. Of the 131
      ESTs, 102 unique ESTs were differentially expressed and classified into 10
      functional categories. The results showed that UVA radiation induces expression
      of genes related to stress and defense response and metabolism. Potential
      transcription factor binding motifs upstream of these genes are associated with
      multiple signaling pathways that may help the insect cope with the stress of UVA
      radiation. To our knowledge, this is the first analysis of insect response to UVA
      radiation at the transcriptional level. Our results reveal that UVA radiation
      influences the expression profiles of stress-responsive genes and provide further
      insights into the mechanisms of adaptive response to UVA radiation stress. 

PMID- 24331623
TI  - Impact of host plant resistance on the tritrophic interactions between wheat
      genotypes, Schizaphis graminum (Homoptera: Aphididae), and Coccinella
      septempunctata (Coleoptera: Coccinellidae) using molecular methods.
AB  - The objective of the current study was to evaluate the impact of wheat resistance
      on digestibility of Schizaphis graminum (Rondani) in the Coccinella
      septempunctata L. gut. Four wheat genotypes including an ancient wheat species
      (Einkorn) and three Iranian wheat genotypes (Azadi, Ommid, and Moghan2) were
      used. Einkorn was found to be a highly resistant species, while Azadi, Ommid, and
      Moghan2 were characterized as resistant, semiresistant, and susceptible
      genotypes, respectively, based on some biological parameters of S. graminum on
      these plants. Adult C. septempunctata starved for 24 h were fed one S. graminum
      reared on the selected wheat genotypes. A semiquantitative polymerase chain
      reaction technique using specific primers for the gene cytochrome oxidase II
      (COII) of S. graminum showed a significant effect of plant resistance on S.
      graminum DNA disappearance time. The DNA half-lives of S. graminum fed on
      Einkorn, Azadi, Ommid, and Moghan2 in C. septempunctata gut was 3.3, 3.6, 4.8,
      and 6.7 h, respectively. The findings suggest that digestibility of S. graminum
      fed on resistant plant genotypes is higher than those fed on susceptible plants
      because of the lighter weights and smaller sizes of the first. This phenomenon
      could result in faster ingestion of S. graminum by C. septempunctata on these
      resistant plants. It is also possible that some metabolites found differentially
      in Einkorn and Azadi genotypes may have affected S. graminum quality as a food
      for C. septempunctata. 

PMID- 24331624
TI  - Temporary stent scaffolding during aneurysm coiling.
AB  - We report a case of temporary Solitaire FR stent (Covidien, Mansfield, MA, USA)
      scaffolding to reduce coil herniation during embolization of a large neck
      anterior communicating artery aneurysm. In contrast to classic stent-assisted
      coiling, the fully retrievable stent is recaptured prior to detachment of the
      last coil. The presented technical nuance hence does not require institution of
      prolonged antiplatelet coverage. But the door is left open for coil-repositioning
      in case of coil basket instability. Permanent stent redeployment remains a fall
      back option if critical hardware conflict occurs. In comparison to classic
      balloon remodeling, the presented method may offer easier distal access,
      particularly in tortuous arterial anatomy. Temporary occlusion of the parent
      artery, side branches, and perforators is also avoided. Given its specific
      potential advantages, temporary stent scaffolding using the fully retrievable
      Solitaire FR device may find its niche as a bailout option, primarily in a very
      specific subset of distally located wide neck aneurysms.

PMID- 24331625
TI  - Risk factors for the development of adjacent segment disease following anterior
      cervical arthrodesis for degenerative cervical disease: comparison between fusion
      methods.
AB  - This study aimed to determine the risk factors for developing adjacent segment
      disease (ASDz) after anterior cervical arthrodesis for the treatment of
      degenerative cervical disease by analyzing patients treated with various fusion
      methods. We enrolled 242 patients who had undergone anterior cervical fusion for
      degenerative cervical disease, and had at least 5years of follow-up. We evaluated
      the development of ASDz and the rate of revision surgery. To identify the risk
      factors for ASDz, the sagittal alignment, spinal canal diameter, range of motion
      of the cervical spine, number of fusion segments, and fusion methods were
      evaluated. The patients were divided into three groups according to the fusion
      method: Group A contained patients who had received autogenous bone graft only
      (53 patients), Group B contained patients who received autogenous bone graft and
      plate augmentation (62 patients), and Group C contained patients who underwent
      cage and plate augmentation (127 patients). ASDz occurred in 33 patients, of whom
      19 required additional surgery. The risk of developing ASDz was significantly
      higher in male patients (p=0.043), patients whose range of motion of the cervical
      spine was >30 degrees  (p=0.027), and patients with spinal canal stenosis
      (p=0.010). The rate of development of ASDz was not different depending on the
      number of fusion segments. The rate of development of ASDz was 41.5% in Group A,
      9.6% in Group B, and 5.51% in Group C (p=0.03). In patients who underwent
      anterior cervical arthrodesis for degenerative disease, the occurrence of ASDz
      was related to age, the cervical spine range of motion, and spinal canal
      stenosis. Additional plate augmentation for anterior cervical arthrodesis surgery
      can lower the rate of ASDz development.

PMID- 24331626
TI  - Primary leptomeningeal melanoma.
AB  - Primary melanoma of the central nervous system is a rare melanocytic tumor
      typically located in the leptomeninges. We report a 57-year-old woman with an
      intracranial leptomeningeal melanoma who presented with myoclonic seizures. Brain
      CT scan and MRI revealed a hemorrhagic intracranial tumor. The tumor was
      completely removed and leptomeningeal melanoma was proven pathologically. Follow
      up imaging studies up to 19 months showed no recurrence of the disease. Here we
      present radiological, gross, and pathological images of leptomeningeal melanoma,
      discuss its characteristics, and review the relevant literature.

PMID- 24331627
TI  - [Effect of hepatitis B virus X protein on suppressor of cytokine signaling-1
      expression].
AB  - OBJECTIVE: To investigate the effect of hepatitis B virus-encoded X protein (HBx)
      on the expression of host-encoded suppressor of cytokine signaling-1 (SOCS-1) and
      to explore the possibility of an underlying mechanism involving modulation of CpG
      island methylation in the SOCS-1 gene promoter. METHODS: The immortalized human
      derived non-tumor liver cell line QSG7701 was transfected with a recombinant HBx
      plasmid (pcDNA-X) or an empty vector control plasmid (pcDNA3.0) and stably
      transfected clones were selected by G418 resistance screening. Untransfected
      cells served as negative controls. Expression of SOCS-1 mRNA and protein was
      detected by real-time quantitative PCR and western blotting. The methylation
      status of SOCS-1 was detected by methylation-specific PCR (MSP). The significance
      of intergroup differences was analyzed by one-way ANOVA or pairwise comparison
      with post-hoc LSD test. RESULTS: SOCS-1 mRNA level was significantly lower in the
      pcDNA-X/QSG7701 cells compared to that in the pcDNA3.0/QSG7701 and untransfected
      cells (0.3249+/-0.0536 vs. 1.0543+/-0.1937 and 1.00; F = 19.6, P = 0.042). SOCS-1
      protein level was similarly lower in the pcDNA-X/QSG7701 cells (0.1496+/-0.0106
      vs. 0.1984+/-0.0438 and 0.2152+/-0.0816; F = 19.4, P = 0.048). The SOCS-1
      promoter region showed methylation only in the pcDNA-X/QSG7701 cells. CONCLUSION:
      HBx-expressing human hepatocytes have down-regulated SOCS-1 expression, both at
      the mRNA and protein levels, and this effect corresponds to increased methylation
      in the SOCS-1 promoter region harboring CpG islands.

PMID- 24331628
TI  - [Clinical value of iodine [131I] metuximab infusion combined with TACE for
      treatment of patients with post-intervention relapse of mid or advanced stage
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the clinical value of iodine[131I] metuximab infusion
      combined with transcatheter arterial chemoembolization (TACE) for treating cases
      of post-intervention relapse of mid or advanced stage hepatocellular carcinoma
      (HCC). METHODS: Sixty patients who were diagnosed between March 2009 and June
      2010 with relapse of mid or advanced stage HCC following previous intervention
      with various standard clinical methods were recruited for study. The patients
      were randomly and equally divided into a control treatment group (CG; receiving
      TACE therapy alone) and an experimental treatment group (TG; receiving TACE
      combined with iodine [131I] metuximab injection). For all patients, licartin was
      first perfused into the tumor feeding artery and then the TACE procedure was
      performed 20 min later. Liver function markers and routine blood parameters,
      including alpha-fetoprotein (AFP) and clotting time, were examined at one week
      and one month after the treatment. Enhanced computed tomography or magnetic
      resonance imaging of the liver was performed at one month after treatment and
      thereafter on a bi-monthly follow-up schedule. The World Health Organization's
      tumor evaluation standard was used to assess the therapeutic effects in each
      group. Results of laboratory tests (pre- and post-treatment), reported
      complications, and side-effects were evaluated for their contributions to time of
      tumor progression (TTP) and survival time. RESULTS: Patients in the TG and CG
      groups had similar blood cell counts at pre-operative and 1-week postoperative
      time points. The TG group showed a significantly reduced level of AFP following
      treatment, but it was not significantly different from the level in the CG group.
      The TG group did however show significantly different levels of liver functional
      parameters (all P less than 0.05) and significantly higher TTP (4.84+/-4.11 vs.
      CG: 2.54+/-2.08 months; t = -2.13, P less than 0.05) and average survival time
      (7.05 vs. 5.15 months; x2 = 4.24, P = 0.039). The rates of partial response (PR),
      slight remission (MR), unchanged status (SD) and progressive disease (PD) were
      16.7%, 37.5%, 25.0% and 20.8% in the TG group, and 8.7%, 17.4%, 21.7% and 52.2%
      in the CG group. The therapeutic effect rate (CR + PR + MR) and reaction rate (CR
      + PR + MR + SD) was significantly different between the two groups (P = 0.048).
      No serious adverse effects were reported. CONCLUSION: TACE combined with iodine
      [131I] metuximab injection is a safe and effective procedure for prolonging the
      survival and TTP of patients with HCC relapse following prior therapeutic
      intervention.

PMID- 24331629
TI  - [Prevalence of nutritional risk among in-patients with liver diseases in Beijing,
      China].
AB  - OBJECTIVE: To investigate the prevalence of nutritional risk and malnutrition
      among in-patients with liver diseases in Beijing, China, and to evaluate the
      relationship between nutritional risk and prognosis. METHODS: A total of 331 in
      patients with liver diseases under care at the Artificial Liver Center of Beijing
      Youan Hospital were consecutively enrolled for study between April 2012 and
      December 2012. Nutritional status was determined by calculating each patient's
      ratio of real weight to clinically ideal weight, the triceps skin fold (TSF), and
      the mid-upper arm muscle circumference (MAMC). Nutritional risk was estimated
      using the Nutritional Risk Screening questionnaire 2002 (NRS-2002). In addition,
      each patient's Child-Pugh stage, body mass index (BMI), power of gripping, serum
      albumin and pre-albumin levels, lymphocyte count, hospital length of stay,
      complications, alcoholism history, and outcome after discharge were recorded for
      analysis. RESULTS: One-hundred-and-thirteen of the patients (34.1%) were defined
      as at nutritional risk upon hospital admission. The ratio of nutritional risk was
      lowest in patients with chronic hepatitis (17.0%) and highest in patients with
      acute on chronic liver failure (56.5%). The ratios of malnutrition evaluated by
      TSF and MAMC were 36.9% and 38.7%, respectively. Among the patients with liver
      cirrhosis or hepatocellular carcinoma, the ratio of Child-Pugh stage C was higher
      for individuals defined as at nutritional risk than for those without. When TSF
      based ratio of malnutrition was higher for individuals with a history of
      alcoholism than for those without. BMI, power of gripping, serum albumin level,
      serum pre-albumin level, and lymphocyte count were all lower for individuals
      defined as at nutritional risk than for those without. Hospital stay, ratio of
      complication onset, and ratio of death were all higher for individuals defined as
      at nutritional risk than for those without. CONCLUSION: TSF and MAMC can be used
      to evaluate the nutritional status of in-patients with liver diseases. Patients
      with nutritional risk (as determined by the NRS-2002) have poorer prognosis and
      may benefit from nutritional intervention.

PMID- 24331630
TI  - [Enhanced nutritional therapy may promote wound healing after endoscopic therapy
      in patients with liver cirrhosis and esophageal varices].
AB  - OBJECTIVE: To investigate the effect of enhanced nutritional therapy on wound
      healing after endoscopic therapy in patients with liver cirrhosis and esophageal
      varices. METHODS: Fifty patients with liver cirrhosis and esophageal varices were
      randomly divided into an enhanced nutritional therapy group (n = 25) and a
      control group (n = 25). The enhanced nutritional therapy group received one week
      of enhanced nutritional supplementation, including liver nutritional elements,
      prior to routine endoscopic therapy. The routine without any change to their
      diet. The rate of transformation and status of wound healing of esophageal
      varices were compared between the two groups. RESULTS: The ratio of ulcers
      occurring at the injection site was lower in the enhanced nutrition group than in
      the control group (16/25 vs. 23/25; x2 = 5.711, P = 0.017). The enhanced
      nutrition group had only one case of minimal bleeding occurring during endoscopy
      as compared to the seven cases of bleeding in the control group (x2 = 5.357, P =
      0.021). On average, the enhanced nutrition group required less sessions of
      endoscopic treatment to achieve eradication of esophageal varices than the
      control group (3.8 vs. 4.1; t = 2.069, P = 0.044). CONCLUSION: Pre-endoscopic
      enhanced nutritional therapy may benefit patients with liver cirrhosis and
      esophageal varices by promoting recovery of procedure-related local tissue injury
      and occlusion of varices.

PMID- 24331631
TI  - [Risk factors of hepatorenal syndrome in patients with acute on chronic liver
      failure].
AB  - OBJECTIVE: To identify the risk factors of hepatorenal syndrome in patients with
      hepatitis B virus (HBV)-related acute-on-chronic liver failure(ACLF). METHODS: A
      total of 726 hospitalized patients with HBV-ACLF were retrospectively analyzed.
      Data of demographic and clinical parameters (sex, age, family history, and
      presence of liver cirrhosis and diabetes), common complications (spontaneous
      bacterial peritonitis, pulmonary infection, hepatic encephalopathy, and upper
      gastrointestinal hemorrhage), and baseline biochemical parameters (albumin,
      globulin, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate
      aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, cholesterol,
      cholinesterase, K+, Na+, plasma thromboplastin antecedent, alpha-fetoprotein, HBV
      DNA, white blood cell count, hemoglobin, and platelet count) were collected from
      the medical records database. Univariate and multiple regression analyses were
      performed to determine the risk factors of hepatorenal syndrome. RESULTS:
      Multiple logistic regression analysis indicated that upper gastrointestinal
      hemorrhage [risk (R) = 1.313, relative hazard (RH) = 3.716, 95% confidence
      interval (CI): 2.156-6.404], hepatic encephalopathy (R = 1.120, RH = 3.065, 95%
      CI: 1.900-4.945), spontaneous bacterial peritonitis (R = 1.005, RH = 2.733, 95%
      CI: 1.379-5.417), pulmonary infection (R = 1.051, RH = 2.862, 95% CI: 1.783
      4.592), and white blood cell count (R = 0.056, RH = 1.058, 95% CI: 1.010-1.107)
      were independent risk factors for hepatorenal syndrome development in patients
      with HBV-ACLF. CONCLUSION: Several risk factors were significantly associated
      with the development of hepatorenal syndrome in HBV-ACLF, including upper
      gastrointestinal hemorrhage, hepatic encephalopathy, spontaneous bacterial
      peritonitis, pulmonary infection, and elevated white blood cell count.

PMID- 24331633
TI  - [Expression of aquaporin 3 and aquaporin 9 is regulated by oleic acid through the
      PI3K/Akt and p38 MAPK signaling pathways].
AB  - OBJECTIVE: To study the effect of oleic acid (OA) on expression of
      aquaglyceroporin genes, AQP3 and AQP9, in hepatocyte steatosis and to investigate
      the underlying molecular mechanisms using an in vitro system. METHODS: HepG2
      cells were treated with OA at different concentration to establish in vitro
      models of nonalcoholic hepatocyte steatosis. The corresponding extents of hepatic
      steatosis modeling were assessed by oil red O staining and optical density (OD)
      measurements of the intracellular fat content. The model lines were then treated
      with inhibitors of the PI3K/Akt and p38 MAPK signaling pathway factors and
      effects on AQP3/9 expression was measured by real time RT-PCR and western
      blotting. RESULTS: The fat concentration, indicative of hepatic steatosis,
      increased in conjunction with increased concentrations of OA (0 less than 250
      less than 500 mumol/L). OA exposure also down-regulated AQP3 mRNA and up
      regulated AQP9 mRNA levels in a concentration-dependent manner. The most robust
      changes in expression occurred in response to the 500 mumol/L concentration of OA
      for both AQP3 (0.47+/-0.18; t = 4.5450, P less than 0.05) and AQP9 (1.57+/-0.21;
      t = 3.0306, P less than 0.05). Treatment with OA + PI3K pathway inhibitor
      (LY294004) significantly decreased AQP9 mRNA expression (4.55+/-0.62) as compared
      to the control group (1.00+/-0.10; t = 9.7909, P less than 0.01), that 500
      mumol/L OA group (2.43+/-0.53; t = 4.5018, P less than 0.05), and the LY294002
      group (1.90+/-0.16; t = 7.1683, P less than 0.01). Treatment with p38 MAPK
      pathway inhibitor (SB230580) significantly increased the OA-suppressed level of
      AQP3 mRNA to the level detected in the control group (1.27+/-0.11; t = 5.7455, P
      less than 0.01) and decreased the OA-stimulated AQP9 mRNA (0.38+/-0.09; t =
      6.5727, P less than 0.01). No significant changes in mRNA expression of AQP3/9
      were observed with inhibition of the ERK1/2 and JNK signal transduction pathways.
      The OA-induced changes in protein expression levels of AQR3 and AQP9 followed a
      similar trend of the genes. Finally, OA suppressed the level of phosphorylated
      Akt (from 0.21+/-0.02 to 0.13+/-0.03; t = 3.8431, P less than 0.05) but elevated
      the level of phosphorylated p38 (from 0.58+/-0.06 to 1.02+/-0.10; t = 12.5289, P
      less than 0.01). Again, OA treatment produced no significant affect on ERK1/2 and
      JNK phosphorylation. CONCLUSION: OA down-regulates AQP3 expression by stimulating
      the p38 MAPK signaling pathway, and up-regulates the AQP9 by blocking the
      PI3K/Akt pathway and activating the p38 MAPK signaling pathway.

PMID- 24331632
TI  - [Synergistic action of 4-hydroxynonenal and tumor necrosis factor involving the
      NF-kB/IkBa signaling pathway in alcohol-induced liver injury].
AB  - OBJECTIVE: To investigate the effects and mechanism of intracellular 4
      hydroxynonenal (4-HNE) accumulation on tumor necrosis factor (TNF)-induced
      hepatotoxicity in alcoholic liver disease (ALD). METHODS: An ALD model was
      established in male C57BL/6 mice (6-8 weeks old) by feeding an ethanol-containing
      diet for 5 weeks; mice given regular (non-ethanol) diet served as controls. ALD
      related changes in 4-HNE and TNF levels were detected by western blotting. The
      underlying mechanisms of this molecular effect were examined by pre-treating
      HepG2 cells with 4-HNE followed by exposure to various concentrations of TNF.
      Effects on cell death were evaluated by MTT assay. Effects on TNF-mediated
      upstream factors' expression were detected by ELISA, western blotting, and real
      time PCR. Effects on the TNF-induced inhibitor of NF-kB (IkBa) activity
      (phosphorylation status) and its formation of adducts were detected by western
      blotting and immunoprecipitation. RESULTS: ALD mice showed increased hepatic 4
      HNE and TNF levels, and the increases were associated with extent of liver
      injury. Cell culture studies revealed that 4-HNE, at non-toxic concentrations,
      sensitized hepatocytes to TNF killing, which was associated with suppressed NF-kB
      trans activity. Furthermore, 4-HNE prevented phosphorylation of IkBa without
      affecting upstream IkB kinase activity. The ALD-enhanced 4-HNE content was found
      to associated with increased formation of 4-HNE-IkBa adduction for both the 4-HNE
      - treated hepatocytes in culture and in the livers of ALD mice. CONCLUSION:
      Alcohol-induced increase in 4-HNE accumulation represents a potent and clinically
      relevant mechanism of sensitizing hepatocytes to TNF-induced toxicity. These data
      support the notion that decreasing or eliminating accumulated intracellular 4-HNE
      can serve as a potential therapeutic option for ALD.

PMID- 24331634
TI  - [Protective effect of recombinant TM-N and recombinant soluble RAGE in a mouse
      model of acute hepatic failure].
AB  - OBJECTIVE: To evaluate the roles of N-terminal lectin-like domain of
      thrombomodulin (TM-N) and receptor for advanced glycation end products (RAGE) in
      acute hepatic failure using a mouse model system. METHODS: Acute hepatic failure
      was induced in Kunming mice by intraperitoneal injection of D-galactosamine (D
      Galn at 600 mg/kg) and lipopolysaccharide (LPS at 5 mug/kg) and mice were divided
      into groups for injection with saline, recombinant (r)TM-N protein, or
      recombinant soluble (rs)RAGE protein. Unmanipulated model mice served as the
      negative controls. Effects on liver expression of high mobility group box-1
      (HMGB1) were detected by immunohistochemistry and real time RT-PCR. Effects on
      serum levels of tumor necrosis factor-alpha (TNFa) and interleukin-1 beta (IL)-1b
      were quantified by ELISA. RESULTS: Treatment with rTM-N and rsRAGE both
      alleviated the acute liver damage induced by D-Galn/LPS exposure, and decreased
      the hepatic expression of HMGB1 as well as the serum levels of TNFa and IL-1b.
      CONCLUSION: Intraperitoneal delivery of rTM-N and rsRAGE can alleviate acute
      liver damage by modulating the expression of necrosis- and inflammation-related
      factors.

PMID- 24331635
TI  - [Effects of antihistamine treatment on immune function in rats with experimental
      hepatitis].
AB  - OBJECTIVE: To investigate the effects of antihistamine treatment on immune
      function in rats with experimental hepatitis. METHODS: Thirty Wistar rats were
      randomly allocated into three groups:experimental hepatitis group (EH group),
      antihistamine treatment group (AH group) and normal control group (NC group).
      Rats in the EH group received the subcutaneous injection of 40% carbon
      tetrachloride oil solution and were fed on diet with low-protein, low-choline,
      high-fat and high-alcohol,while rats in the AH group received antihistamine
      treatment(ketotifen + vitamin C) additionally.They were sacrificed after 4 weeks,
      and the levels of serum alanine aminotransferase(ALT), total bilirubin (TBil),
      histamine(HA), IFNgamma, IL-12, IL-4 and IL-10 were determined. The levels of IL
      12 mRNA and IFN-gamma mRNA in liver tissue were determined via real-time reverse
      transcriptional polymerase chain reaction(RT-PCR). RESULTS: (1) Compared to the
      NC group, in the EH group, the levels of ALT, TBil, and circulating and
      intrahepatic HA were significantly increased(P less than 0.05); intrahepatic HA
      were significantly decreased(P less than 0.05) after antihistamine treatment. (2)
      Compared to the NC group, in the EH group, the levels of IL-4, IL-10 were
      significantly increased((0.504+/-0.202)ng/ml and (29.025+/-1.478) pg/ml vs
      (0.811+/-0.244)ng/ml and (33.72+/-4.293)pg/ml respectively, P less than 0.05),
      and the levels of IL-12 were decreased ((6.515+/-2.893)pg/ml vs (3.519+/
      1.113)pg/ml, P less than 0.05); and after antihistamine treatment the levels of
      IL-4 and IL-10 were significantly decreased (were (0.423+/-0.168)ng/ml and
      (30.412+/-3.275)pg/ml, P less than 0.05), the levels of IL-12 were significantly
      increased (P less than 0.05), but the level of IFNgamma had no significance (P
      more than 0.05). The levels of intrahepatic IL-12 mRNA and IFNgamma mRNA had
      similar results. CONCLUSION: Antihistamine treatment may improve liver function
      and correct Th1/Th2 unbalance.

PMID- 24331636
TI  - Nelson Mandela: from Umkhonto we Sizwe to AIDS.

PMID- 24331638
TI  - Cerebral microembolism during transradial coronary angiography: comparison
      between single and double catheter strategy.

PMID- 24331637
TI  - The effect of social anxiety on urge and craving among smokers with and without
      anxiety disorders.
AB  - BACKGROUND: Despite the often social nature of smoking, relatively little
      research has been conducted on the relationship between smoking and social
      anxiety disorder (SAD). METHOD: Participants (N=99) included 34 smokers without
      current mental health disorders, 37 smokers with SAD, and 28 smokers who met
      criteria for other anxiety disorder diagnoses (e.g., panic disorder or
      generalized anxiety disorder, but not SAD). Nicotine and placebo patches were
      administered to participants in a counterbalanced manner across two assessment
      days. Urge and craving were assessed before and after a 5-h nicotine
      absorption/deprivation period. RESULTS: Compared to smokers without current
      mental health disorders, smokers with SAD did not report greater nicotine
      dependence, but did endorse greater motivation to use nicotine to avoid negative
      outcomes. In addition, after controlling for demographic variables, smoking
      characteristics, pre-deprivation urge and craving, and other anxiety/depression
      symptoms, social anxiety symptoms uniquely predicted urge and craving in the
      placebo patch condition; however, social anxiety had no influence on urge and
      craving in the nicotine patch condition. CONCLUSIONS: These findings suggest that
      one potential reason that smokers with SAD may have worse cessation outcomes is
      that they may experience higher levels of craving and urge to smoke during quit
      attempts. Thus, during a quit attempt, particularly in the absence of nicotine
      replacement therapy, smokers with SAD are likely to benefit from additional
      treatment aimed at managing or reducing their social anxiety symptoms.

PMID- 24331640
TI  - Beyond uvulopalatopharyngoplasty for obstructive sleep apnoea: single surgeon
      case series of contemporary airway reconstruction.
AB  - OBJECTIVE: Adult patients with obstructive sleep apnoea can be a therapeutic
      surgical challenge if other treatments fail or are rejected. We report the
      outcomes of a series of 17 patients for whom standard device-based treatments
      failed or could not be used. These patients were considered unsuitable for a
      lesser operation and therefore underwent multilevel upper airway reconstruction.
      METHOD: Data from 17 consecutive patients were collected prospectively. This
      included pre- and post-surgery findings for clinical assessments, body mass
      index, sleep questionnaires, and laboratory polysomnograms. Patients underwent a
      combination of modified uvulopalatopharyngoplasty, transpalatal advancement and
      various tongue reduction procedures. RESULTS: Analyses revealed statistically and
      clinically significant reductions in: mean apnoea-hypopnoea index scores (from
      36.3 pre-operatively to 14.5 post-operatively, p < 0.001), mean Epworth
      sleepiness scale scores (from 11.3 to 5.3, p < 0.001) and mean snoring severity
      scores (from 6.9 to 1.3, p < 0.001). Body mass index remained unchanged.
      CONCLUSION: Multilevel upper airway reconstructive surgery was associated with
      large reductions in both objective and patient-centred subjective measures of
      obstructive sleep apnoea severity.

PMID- 24331639
TI  - Lung function and gas exchange in Eisenmenger syndrome and their impact on
      exercise capacity and survival.
AB  - BACKGROUND: Eisenmenger physiology may contribute to abnormal pulmonary mechanics
      and gas exchange and thus impaired functional capacity. We explored the
      relationship between lung function and gas exchange parameters with exercise
      capacity and survival. METHODS: Stable adult patients with Eisenmenger syndrome
      (N=32) were prospectively studied using spirometry, lung volumes, diffusion
      capacity, and blood gas analysis, as well as same day measurement of 6-minute
      walk distance and cardiopulmonary maximal treadmill exercise. Patients were
      followed prospectively to determine survival (7.4 +/- 0.5 years). Abnormalities
      were identified and appropriate comparisons were made between affected and
      unaffected individuals between respiratory mechanics, exercise function, and
      survival. RESULTS: Obstruction (FEV1/FVC ratio <0.70) was found in 13 patients
      (41%), who were older but not otherwise different. Restriction was uncommon.
      Diffusion transfer coefficient, which was <80% in half the patients, correlated
      with exercise duration (r=0.542, P=0.005), and was worse in non-survivors (N=6).
      Nearly all patients had a compensated respiratory alkalosis (PaCO2 32 +/- 4.4 mm
      Hg). PaCO2 was less reduced in older patients (r=0.438, P=0.022), and correlated
      independently with exercise duration (R=-0.463, P=0.03), yet PaO2, not PaCO2, was
      associated with survival. CONCLUSIONS: Eisenmenger patients show evidence of
      obstructive lung disease, diffusion abnormalities, and hypocapnia; likely from
      hyperventilation. Understanding expected lung mechanics and gas exchange may
      facilitate more appropriate clinical management.

PMID- 24331641
TI  - [Is there any place for art in "Chirurgie de la Main"?].

PMID- 24331642
TI  - High prevalence of spotted fever group rickettsiae in Amblyomma variegatum from
      Uganda and their identification using sizes of intergenic spacers.
AB  - The spotted fever group (SFG) rickettsiae are obligate intracellular bacteria
      transmitted by ticks that cause several tick-borne rickettsioses in humans
      worldwide. This study was intended to determine the prevalence of SFG rickettsiae
      in Amblyomma variegatum from 7 districts across Uganda. In addition to sequencing
      of gltA and ompA genes, identification of Rickettsia species based on the sizes
      of highly variable intergenic spacers, namely, dksA-xerC, mppA-purC, and rpmE
      tRNA(fMet) was carried out. Application of multiplex PCR for simultaneous
      amplification of 3 spacers combined with capillary electrophoresis separation
      allowed simple, accurate, and high-throughput fragment sizing with considerable
      time and cost savings. Rickettsia genus-specific real-time PCR detected 136
      positives out of 140 samples, giving an overall prevalence of 97.1%. Most samples
      (n=113) had a size combination of 225, 195, and 341 bp for dksA-xerC, mppA-purC,
      and rpmE-tRNA(fMet), respectively, which was identical to that of R. africae, a
      causative agent of African tick bite fever. In addition, several samples had size
      variants in either dksA-xerC or rpmE-tRNA(fMet). Nonetheless, the partial
      sequences of gltA and ompA genes of samples of all size combinations showed the
      greatest similarity to R. africae (99.3-100% for gltA and 98.1-100% for ompA).
      Given these results, it is highly possible that the tested ticks were infected
      with R. africae or closely related species. This is a first report on molecular
      genetic detection of R. africae and its high endemicity in Uganda. Clinicians in
      this country should be aware of this pathogen as a cause of non-malarial febrile
      illness. This study provided a starting point for the development of Rickettsia
      species identification based on the sizes of intergenic spacers. The procedure is
      simple, rapid, and cost-effective to perform; hence it might be particularly well
      suited for preliminary species identification in epidemiological investigations.
      The results may be more detailed and reliable when simultaneous sequencing
      analysis is performed.

PMID- 24331643
TI  - Disgust, insula, immune signaling, and addiction.

PMID- 24331644
TI  - Nucleus accumbens plasticity underlies multifaceted behavioral changes associated
      with addiction.

PMID- 24331645
TI  - Biased behaviors: towards understanding vulnerability and resilience factors in
      addictions.

PMID- 24331646
TI  - Thoughts on the future of research, teaching, and testing in the biological
      sciences of radiation oncology.

PMID- 24331647
TI  - The anatomy of radiation oncology residency training.

PMID- 24331648
TI  - An Early X-ray Tube.

PMID- 24331649
TI  - Beyond the standard curriculum: a review of available opportunities for medical
      students to prepare for a career in radiation oncology.
AB  - PURPOSE: To review currently available opportunities for medical students to
      supplement their standard medical education to prepare for a career in radiation
      oncology. METHODS AND MATERIALS: Google and PubMed were used to identify existing
      clinical, health policy, and research programs for medical students in radiation
      oncology. In addition, results publicly available by the National Resident
      Matching Program were used to explore opportunities that successful radiation
      oncology applicants pursued during their medical education, including obtaining
      additional graduate degrees. RESULTS: Medical students can pursue a wide variety
      of opportunities before entering radiation oncology. Several national specialty
      societies, such as the American Society for Radiation Oncology and the
      Radiological Society of North America, offer summer internships for medical
      students interested in radiation oncology. In 2011, 30% of allopathic senior
      medical students in the United States who matched into radiation oncology had an
      additional graduate degree, including PhD, MPH, MBA, and MA degrees. Some medical
      schools are beginning to further integrate dedicated education in radiation
      oncology into the standard 4-year medical curriculum. CONCLUSIONS: To the
      authors' knowledge, this is the first comprehensive review of available
      opportunities for medical students interested in radiation oncology. Early
      exposure to radiation oncology and additional educational training beyond the
      standard medical curriculum have the potential to create more successful
      radiation oncology applicants and practicing radiation oncologists while also
      promoting the growth of the field. We hope this review can serve as guide to
      radiation oncology applicants and mentors as well as encourage discussion
      regarding initiatives in radiation oncology opportunities for medical students.

PMID- 24331650
TI  - Radiation oncology medical student clerkship: implementation and evaluation of a
      bi-institutional pilot curriculum.
AB  - PURPOSE: To develop and evaluate a structured didactic curriculum to complement
      clinical experiences during radiation oncology clerkships at 2 academic medical
      centers. METHODS AND MATERIALS: A structured didactic curriculum was developed to
      teach fundamentals of radiation oncology and improve confidence in clinical
      competence. Curriculum lectures included: (1) an overview of radiation oncology
      (history, types of treatments, and basic clinic flow); (2) fundamentals of
      radiation biology and physics; and (3) practical aspects of radiation treatment
      simulation and planning. In addition, a hands-on dosimetry session taught
      students fundamentals of treatment planning. The curriculum was implemented at 2
      academic departments in 2012. Students completed anonymous evaluations using a
      Likert scale to rate the usefulness of curriculum components (1=not at all,
      5=extremely). Likert scores are reported as (median [interquartile range]).
      RESULTS: Eighteen students completed the curriculum during their 4-week rotation
      (University of Chicago n=13, Harvard Longwood Campus n=5). All curriculum
      components were rated as extremely useful: introduction to radiation oncology (5
      [4-5]); radiation biology and physics (5 [5-5]); practical aspects of radiation
      oncology (5 [4-5]); and the treatment planning session (5 [5-5]). Students rated
      the curriculum as "quite useful" to "extremely useful" (1) to help students
      understand radiation oncology as a specialty; (2) to increase student comfort
      with their specialty decision; and (3) to help students with their future
      transition to a radiation oncology residency. CONCLUSIONS: A standardized
      curriculum for medical students completing a 4-week radiation oncology clerkship
      was successfully implemented at 2 institutions. The curriculum was favorably
      reviewed. As a result of completing the curriculum, medical students felt more
      comfortable with their specialty decision and better prepared to begin radiation
      oncology residency.

PMID- 24331651
TI  - A national radiation oncology medical student clerkship survey: didactic
      curricular components increase confidence in clinical competency.
AB  - PURPOSE: Students applying to radiation oncology residency programs complete 1 or
      more radiation oncology clerkships. This study assesses student experiences and
      perspectives during radiation oncology clerkships. The impact of didactic
      components and number of clerkship experiences in relation to confidence in
      clinical competency and preparation to function as a first-year radiation
      oncology resident are evaluated. METHODS AND MATERIALS: An anonymous, Internet
      based survey was sent via direct e-mail to all applicants to a single radiation
      oncology residency program during the 2012-2013 academic year. The survey was
      composed of 3 main sections including questions regarding baseline demographic
      information and prior radiation oncology experience, rotation experiences, and
      ideal clerkship curriculum content. RESULTS: The survey response rate was 37% (70
      of 188). Respondents reported 191 unique clerkship experiences. Of the
      respondents, 27% (19 of 70) completed at least 1 clerkship with a didactic
      component geared towards their level of training. Completing a clerkship with a
      didactic component was significantly associated with a respondent's confidence to
      function as a first-year radiation oncology resident (Wilcoxon rank-sum P=.03).
      However, the total number of clerkships completed did not correlate with
      confidence to pursue radiation oncology as a specialty (Spearman rho P=.48) or
      confidence to function as a first year resident (Spearman rho P=.43).
      CONCLUSIONS: Based on responses to this survey, rotating students perceive that
      the majority of radiation oncology clerkships do not have formal didactic
      curricula. Survey respondents who completed a clerkship with a didactic
      curriculum reported feeling more prepared to function as a radiation oncology
      resident. However, completing an increasing number of clerkships does not appear
      to improve confidence in the decision to pursue radiation oncology as a career or
      to function as a radiation oncology resident. These results support further
      development of structured didactic curricula for the radiation oncology
      clerkship.

PMID- 24331652
TI  - Prospective study of local control and late radiation toxicity after
      intraoperative radiation therapy boost for early breast cancer.
AB  - PURPOSE: To report the local recurrence rate and late toxicity of intraoperative
      radiation therapy (IORT) boost to the tumor bed using the Intrabeam System
      followed by external-beam whole-breast irradiation (WBI) in women with early
      stage breast cancer in a prospective single-institution study. METHODS AND
      MATERIALS: Women with breast cancer<=3 cm were recruited between February 2003
      and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost
      was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface.
      This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patients were
      reviewed at regular, predefined intervals. Late toxicities were recorded using
      the Radiation Therapy Oncology Group/European Organization for Research and
      Treatment of Cancer Late Radiation Morbidity Scoring systems. RESULTS: Fifty-five
      patients completed both IORT boost and external-beam WBI. Median follow-up was
      3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence
      or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous
      fibrosis was detected in 29 (53%) and 8 patients (15%), respectively.
      CONCLUSIONS: The use of IORT as a tumor bed boost using kV x-rays in breast
      conserving therapy was associated with good local control but a clinically
      significant rate of grade 2 and 3 subcutaneous fibrosis.

PMID- 24331653
TI  - Local recurrence in women with stage I breast cancer: declining rates over time
      in a large, population-based cohort.
AB  - PURPOSE: To evaluate whether local recurrence (LR) risk has changed over time
      among women with stage I breast cancer treated with breast-conserving therapy.
      METHODS AND MATERIALS: Subjects were 5974 women aged >=50 years diagnosis with
      pT1N0 breast cancer from 1989 to 2006, treated with breast-conserving surgery and
      radiation therapy. Clinicopathologic characteristics, treatment, and LR outcomes
      were compared among 4 cohorts stratified by year of diagnosis: 1989 to 1993
      (n=1077), 1994 to 1998 (n=1633), 1999 to 2002 (n=1622), and 2003 to 2006
      (n=1642). Multivariable analysis was performed, with year of diagnosis as a
      continuous variable. RESULTS: Median follow-up time was 8.6 years. Among patients
      diagnosed in 1989 to 1993, 1994 to 1998, 1999 to 2002, and 2003 to 2006, the
      proportions of grade 1 tumors increased (16% vs 29% vs 40% vs 39%, respectively,
      P<.001). Surgical margin clearance rates increased from 82% to 93% to 95% and
      88%, respectively (P<.001). Over time, the proportions of unknown estrogen
      receptor (ER) status decreased (29% vs 10% vs 1.2% vs 0.5%, respectively,
      P<.001), whereas ER-positive tumors increased (56% vs 77% vs 86% vs 86%,
      respectively, P<.001). Hormone therapy use increased (23% vs 23% vs 62% vs 73%,
      respectively, P<.001), and chemotherapy use increased (2% vs 5% vs 10% vs 13%,
      respectively, P<.001). The 5-year cumulative incidence rates of LR over the 4
      time periods were 2.8% vs 1.7% vs 0.9% vs 0.8%, respectively (Gray's test,
      P<.001). On competing risk multivariable analysis, year of diagnosis was
      significantly associated with decreased LR (hazard ratio, 0.92 per year,
      P=.0003). Relative to grade 1 histology, grades 2, 3, and unknown were associated
      with increased LR. Hormone therapy use was associated with reduced LR.
      CONCLUSION: Significant changes in the multimodality management of stage I breast
      cancer have occurred over the past 2 decades. More favorable-risk tumors were
      diagnosed, and margin clearance and systemic therapy use increased. These changes
      contributed to the observed declining LR rates among patients treated with breast
      conserving therapy.

PMID- 24331654
TI  - Prostate-specific antigen at 4 to 5 years after low-dose-rate prostate
      brachytherapy is a strong predictor of disease-free survival.
AB  - PURPOSE: To determine (1) the prognostic utility of prostate-specific antigen
      (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate
      brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic
      utility of directional trends between PSA levels at 24, 36, and 48 months after
      LDR-PB. METHODS AND MATERIALS: Between 1998 and 2008, 2223 patients with low- and
      intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434
      of these patients was identified with a documented 48mPSA and no evidence of
      disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585)
      was identified with >=72 months of follow-up and documented PSA values at both 24
      and 36 months after implantation. RESULTS: Median follow-up time was 76 months.
      Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for
      patients with 48mPSA<=0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a
      48mPSA threshold of <=0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0%
      for a threshold of <=1.0 versus >1.0 ng/mL, respectively. On multivariate
      analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset
      analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24
      and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients
      had rises over both intervals. Failure rates in these patients were 52%, 79%, and
      100%, respectively. On multivariate analysis, initial PSA, androgen deprivation
      therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but
      together accounted for only ~5% of its total variance. CONCLUSIONS: The 48mPSA
      after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA<=0.4
      ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with
      48mPSA>1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36
      months and from 36 to 48 months were also highly predictive of subsequent
      failure.

PMID- 24331656
TI  - Observational study designs for comparative effectiveness research: an
      alternative approach to close evidence gaps in head-and-neck cancer.
AB  - Comparative effectiveness research (CER) has emerged as an approach to improve
      quality of care and patient outcomes while reducing healthcare costs by providing
      evidence to guide healthcare decisions. Randomized controlled trials (RCTs) have
      represented the ideal study design to support treatment decisions in head-and
      neck (H&N) cancers. In RCTs, formal chance (randomization) determines treatment
      allocation, which prevents selection bias from distorting the measure of
      treatment effects. Despite this advantage, only a minority of patients qualify
      for inclusion in H&N RCTs, which limits the validity of their results to the
      broader H&N cancer patient population seen in clinical practice. Randomized
      controlled trials often do not address other knowledge gaps in the management of
      H&N cancer, including treatment comparisons for rare types of H&N cancers,
      monitoring of rare or late toxicity events (eg, osteoradionecrosis), or in some
      instances an RCT is simply not feasible. Observational studies, or studies in
      which treatment allocation occurs independently of investigators' choice or
      randomization, may address several of these gaps in knowledge, thereby
      complementing the role of RCTs. This critical review discusses how observational
      CER studies complement RCTs in generating the evidence to inform healthcare
      decisions and improve the quality of care and outcomes of H&N cancer patients.
      Review topics include a balanced discussion about the strengths and limitations
      of both RCT and observational CER study designs; a brief description of design
      and analytic techniques to handle selection bias in observational studies;
      examples of observational studies that inform current clinical practices and
      management of H&N cancers; and suggestions for relevant CER questions that could
      be addressed by an observational study design. 

PMID- 24331655
TI  - RTOG 0417: efficacy of bevacizumab in combination with definitive radiation
      therapy and cisplatin chemotherapy in untreated patients with locally advanced
      cervical carcinoma.
AB  - PURPOSE: Radiation Therapy Oncology Group 0417 was a phase II study that explored
      the safety and efficacy of the addition of bevacizumab to chemoradiation therapy.
      The safety results have been previously reported. Herein we report the secondary
      efficacy endpoints of overall survival (OS), locoregional failure (LRF), para
      aortic nodal failure (PAF), distant failure (DF), and disease-free survival
      (DFS). METHODS AND MATERIALS: Eligible patients with bulky Stage IB-IIIB disease
      were treated with once-weekly cisplatin (40 mg/m2) chemotherapy and standard
      pelvic radiation therapy and brachytherapy. Bevacizumab was administered at 10
      mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation. For OS,
      failure was defined as death of any cause and was measured from study entry to
      date of death. LRF was defined as any failure in the pelvis. PAF was defined as
      any para-aortic nodal failure. DF was analyzed both including and excluding PAF.
      DFS was measured from study entry to date of first LRF. DF was measured with or
      without PAF or death. OS and DFS were estimated by the Kaplan-Meier method, and
      LRF and DF rates were estimated by the cumulative incidence method. RESULTS: 49
      eligible patients from 28 institutions were enrolled between 2006 and 2009. The
      median follow-up time was 3.8 years (range, 0.8-6.0 years). The surviving
      patients had a median follow-up time of 3.9 years (range, 2.1-6.0 years). Most
      patients had tumors of International Federation of Gynecology and Obstetrics
      Stage IIB (63%), and 80% were squamous. The 3-year OS, DFS, and LRF were 81.3%
      (95% confidence interval [CI], 67.2%-89.8%), 68.7% (95% CI, 53.5%-79.8%), and
      23.2% (95% CI, 11%-35.4%), respectively. The PAF, DF without PAF, and DF with PAF
      at 3 years were 8.4% (95% CI, 0.4%-16.3%), 14.7% (95% CI, 4.5%-24.9%), and 23.1%
      (95% CI 11.0%-35.2%), respectively. CONCLUSION: In this study, bevacizumab in
      combination with standard pelvic chemoradiation therapy for locally advanced
      cervical cancer showed efficacy results that are promising and may warrant
      further investigation.

PMID- 24331657
TI  - Impact of concomitant chemotherapy on outcomes of radiation therapy for head-and
      neck cancer: a population-based study.
AB  - PURPOSE: Clinical trials have shown that the addition of chemotherapy to
      radiation therapy (RT) improves survival in advanced head-and-neck cancer. The
      objective of this study was to describe the effectiveness of concomitant
      chemoradiation therapy (C-CRT) in routine practice. METHODS AND MATERIALS: This
      was a population-based cohort study. Electronic records of treatment from all
      provincial cancer centers were linked to a population--based cancer registry to
      describe the adoption of C-CRT for head-and-neck cancer patients in Ontario,
      Canada. The study population was then divided into pre- and postadoption cohorts,
      and their outcomes were compared. RESULTS: Between 1992 and 2008, 18,867 patients
      had diagnoses of head-and-neck cancer in Ontario, of whom 7866 (41.7%) were
      treated with primary RT. The proportion of primary RT cases that received C-CRT
      increased from 2.2% in the preadoption cohort (1992-1998) to 39.3% in the
      postadoption cohort (2003-2008). Five-year survival among all primary RT cases
      increased from 43.6% in the preadoption cohort to 51.8% in the postadoption
      cohort (P<.001). Over the same period, treatment-related hospital admissions
      increased significantly, but there was no significant increase in treatment
      related deaths. CONCLUSIONS: C-CRT was widely adopted in Ontario after 2003, and
      its adoption was temporally associated with an improvement in survival.

PMID- 24331658
TI  - Accuracy of computed tomography for predicting pathologic nodal extracapsular
      extension in patients with head-and-neck cancer undergoing initial surgical
      resection.
AB  - PURPOSE: Nodal extracapsular extension (ECE) in patients with head-and-neck
      cancer increases the loco-regional failure risk and is an indication for adjuvant
      chemoradiation therapy (CRT). To reduce the risk of requiring trimodality
      therapy, patients with head-and-neck cancer who are surgical candidates are often
      treated with definitive CRT when preoperative computed tomographic imaging
      suggests radiographic ECE. The purpose of this study was to assess the accuracy
      of preoperative CT imaging for predicting pathologic nodal ECE (pECE). METHODS
      AND MATERIALS: The study population consisted of 432 consecutive patients with
      oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent
      preoperative CT imaging before initial surgical resection and neck dissection.
      Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. RESULTS:
      Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in
      87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%,
      respectively. The sensitivity of radiographic ECE increased from 18.8% for grade
      1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE
      criteria of adjacent structure invasion was a better predictor than irregular
      borders/fat stranding for pECE. CONCLUSIONS: Radiographic ECE has poor
      sensitivity, but excellent specificity for pECE in patients who undergo initial
      surgical resection. PPV and NPV are reasonable for clinical decision making. The
      performance of preoperative CT imaging increased as pECE grade increased.
      Patients with resectable head-and-neck cancer with radiographic ECE based on
      adjacent structure invasion are at high risk for high-grade pECE requiring
      adjuvant CRT when treated with initial surgery; definitive CRT as an alternative
      should be considered where appropriate.

PMID- 24331659
TI  - A phase 2 trial of stereotactic radiosurgery boost after surgical resection for
      brain metastases.
AB  - PURPOSE: To evaluate local control after surgical resection and postoperative
      stereotactic radiosurgery (SRS) for brain metastases. METHODS AND MATERIALS: A
      total of 49 patients (50 lesions) were enrolled and available for analysis.
      Eligibility criteria included histologically confirmed malignancy with 1 or 2
      intraparenchymal brain metastases, age>=18 years, and Karnofsky performance
      status (KPS)>=70. A Cox proportional hazard regression model was used to test for
      significant associations between clinical factors and overall survival (OS).
      Competing risks regression models, as well as cumulative incidence functions,
      were fit using the method of Fine and Gray to assess the association between
      clinical factors and both local failure (LF; recurrence within surgical cavity or
      SRS target), and regional failure (RF; intracranial metastasis outside of treated
      volume). RESULTS: The median follow-up was 12.0 months (range, 1.0-94.1 months).
      After surgical resection, 39 patients with 40 lesions were treated a median of 31
      days (range, 7-56 days) later with SRS to the surgical bed to a median dose of
      1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF
      after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months.
      Patients who went on to receive SRS had a significantly lower incidence of LF
      (P=.008). Other factors associated with improved local control include non-small
      cell lung cancer histology (P=.048), tumor diameter<3 cm (P=.010), and deep
      parenchymal tumors (P=.036). Large tumors (>=3 cm) with superficial dural/pial
      involvement showed the highest risk for LF (53.3% at 12 months). Large
      superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were
      associated with a higher risk of developing RF compared to supratentorial lesions
      (P<.001). CONCLUSIONS: Postoperative SRS is associated with high rates of local
      control, especially for deep brain metastases<3 cm. Tumors>=3 cm with superficial
      dural/pial involvement demonstrate the highest risk of LF.

PMID- 24331660
TI  - Salvage radiosurgery for brain metastases: prognostic factors to consider in
      patient selection.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) is offered to patients for recurrent
      brain metastases after prior brain radiation therapy (RT), but few studies have
      evaluated the efficacy of salvage SRS or factors to consider in selecting
      patients for this treatment. This study reports overall survival (OS),
      intracranial progression-free survival (PFS), and local control (LC) after
      salvage SRS, and factors associated with outcomes. METHODS AND MATERIALS: This is
      a retrospective review of patients treated from 2009 to 2011 with salvage SRS
      after prior brain RT for brain metastases. Survival from salvage SRS and from
      initial brain metastases diagnosis (IBMD) was calculated. Univariate and
      multivariable (MVA) analyses included age, performance status, recursive
      partitioning analysis (RPA) class, extracranial disease control, and time from
      initial RT to salvage SRS. RESULTS: There were 106 patients included in the
      analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2
      metastases were treated per patient (range, 1-12) with a median dose of 21 Gy
      (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5
      months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and
      3 years, respectively. Median PFS was 6.2 months (95% confidence interval
      [CI]=4.9-7.6). Median OS was 11.7 months (95% CI=8.1-13) from salvage SRS, and
      22.1 months from IBMD (95% CI=18.4-26.8). On MVA, age (P=.01; hazard ratio
      [HR]=1.04; 95% CI=1.01-1.07), extracranial disease control (P=.004; HR=0.46; 95%
      CI=0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days
      (P=.001; HR=2.46; 95% CI=1.47-4.09) were predictive of OS. CONCLUSIONS: This
      study demonstrates that patients can have durable local control and survival
      after salvage SRS for recurrent brain metastases. In particular, younger patients
      with controlled extracranial disease and a durable response to initial brain RT
      are likely to benefit from salvage SRS.

PMID- 24331661
TI  - Prognostic value of external beam radiation therapy in patients treated with
      surgical resection and intraoperative electron beam radiation therapy for locally
      recurrent soft tissue sarcoma: a multicentric long-term outcome analysis.
AB  - BACKGROUND: A joint analysis of data from centers involved in the Spanish
      Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to
      investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS)
      patients treated with a multidisciplinary approach. METHODS AND MATERIALS:
      Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%;
      retroperitoneum, 33%) and no distant metastases who underwent radical surgery and
      intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were
      considered eligible for participation in this study. In addition, 62% received
      external beam radiation therapy (EBRT; median dose, 50 Gy). RESULTS: From 1986 to
      2012, a total of 103 patients from 3 Spanish expert IOERT institutions were
      analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year
      local control (LC) was 60%. The 5-year IORT in-field control, disease-free
      survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the
      multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically
      involved margin resection status (P=.04) retained significance in relation to LC.
      With regard to IORT in-field control, only not delivering EBRT to the LR-STS
      retained significance in the multivariate analysis (P=.03). CONCLUSION: This
      joint analysis revealed that surgical margin and EBRT affect LC but that, given
      the high risk of distant metastases, DFS remains modest. Intensified local
      treatment needs to be further tested in the context of more efficient concurrent,
      neoadjuvant, and adjuvant systemic therapy.

PMID- 24331662
TI  - A critical role of the PTEN/PDGF signaling network for the regulation of
      radiosensitivity in adenocarcinoma of the prostate.
AB  - PURPOSE: Loss or mutation of the phosphate and tensin homologue (PTEN) is a
      common genetic abnormality in prostate cancer (PCa) and induces platelet-derived
      growth factor D (PDGF D) signaling. We examined the role of the PTEN/PDGF axis on
      radioresponse using a murine PTEN null prostate epithelial cell model. METHODS
      AND MATERIALS: PTEN wild-type (PTEN+/+) and PTEN knockout (PTEN-/-) murine
      prostate epithelial cell lines were used to examine the relationship between the
      PTEN status and radiosensitivity and also to modulate the PDGF D expression
      levels. PTEN-/- cells were transduced with a small hairpin RNA (shRNA) lentiviral
      vector containing either scrambled nucleotides (SCRM) or sequences targeted to
      PDGF D (shPDGF D). Tumorigenesis and morphogenesis of these cell lines were
      evaluated in vivo via subcutaneous injection of male nude mice and in vitro using
      Matrigel 3-dimensional (3D) culture. Effects of irradiation on clonogenic
      survival, cell migration, and invasion were measured with respect to the PTEN
      status and the PDGF D expression level. In addition, apoptosis and cell cycle
      redistribution were examined as potential mechanisms for differences seen.
      RESULTS: PTEN-/- cells were highly tumorigenic in animals and effectively formed
      foci in 3D culture. Importantly, loss of PDGF D in these cell lines drastically
      diminished these phenotypes. Furthermore, PTEN-/- cells demonstrated increased
      clonogenic survival in vitro compared to PTEN+/+, and attenuation of PDGF D
      significantly reversed this radioresistant phenotype. PTEN-/- cells displayed
      greater migratory and invasive potential at baseline as well as after
      irradiation. Both the basal and radiation-induced migratory and invasive
      phenotypes in PTEN-/- cells required PDGF D expression. Interestingly, these
      differences were independent of apoptosis and cell cycle redistribution, as they
      showed no significant difference. CONCLUSIONS: We propose that PDGF D represents
      a potentially promising target for PCa treatment resistance in the absence of
      PTEN function, and warrants further laboratory evaluation and clinical study.

PMID- 24331663
TI  - Hypoxia-inducible factor pathway inhibition resolves tumor hypoxia and improves
      local tumor control after single-dose irradiation.
AB  - PURPOSE: To study the effects of BAY-84-7296, a novel orally bioavailable
      inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1)
      activity, on hypoxia, microenvironment, and radiation response of tumors. METHODS
      AND MATERIALS: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were
      transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter
      BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals.
      At 7 mm tumors were either excised for Western blot and immunohistologic
      investigations or were irradiated with single doses. After irradiation animals
      were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor
      control was evaluated 150 days after irradiation, and the dose to control 50% of
      tumors (TCD50) was calculated. RESULTS: BAY-84-7296 decreased nuclear HIF-1alpha
      expression. Daily administration of inhibitor for approximately 2 weeks resulted
      in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%,
      P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied
      by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in
      UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced
      only in UT-SCC-5. No significant changes were observed in vascular area or
      necrosis. BAY-84-7296 before single-dose irradiation significantly decreased
      TCD50, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72)
      in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance
      after irradiation did not further decrease TCD50. CONCLUSIONS: BAY-84-7296
      resulted in a marked decrease in tumor hypoxia and substantially reduced
      radioresistance of tumor cells with the capacity to cause a local recurrence
      after irradiation. The data suggest that reduction of cellular hypoxia tolerance
      by BAY-84-7296 may represent the primary biological mechanism underlying the
      observed enhancement of radiation response. Whether this mechanism contributes to
      the improved outcome of fractionated chemoradiation therapy warrants further
      investigation.

PMID- 24331664
TI  - Roles of sensory nerves in the regulation of radiation-induced structural and
      functional changes in the heart.
AB  - PURPOSE: Radiation-induced heart disease (RIHD) is a chronic severe side effect
      of radiation therapy of intrathoracic and chest wall tumors. The heart contains a
      dense network of sensory neurons that not only are involved in monitoring of
      cardiac events such as ischemia and reperfusion but also play a role in cardiac
      tissue homeostasis, preconditioning, and repair. The purpose of this study was to
      examine the role of sensory nerves in RIHD. METHODS AND MATERIALS: Male Sprague
      Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2
      weeks before local image-guided heart x-ray irradiation with a single dose of 21
      Gy. During the 6 months of follow-up, heart function was assessed with high
      resolution echocardiography. At 6 months after irradiation, cardiac structural
      and molecular changes were examined with histology, immunohistochemistry, and
      Western blot analysis. RESULTS: Capsaicin pretreatment blunted the effects of
      radiation on myocardial fibrosis and mast cell infiltration and activity. By
      contrast, capsaicin pretreatment caused a small but significant reduction in
      cardiac output 6 months after irradiation. Capsaicin did not alter the effects of
      radiation on cardiac macrophage number or indicators of autophagy and apoptosis.
      CONCLUSIONS: These results suggest that sensory nerves, although they play a
      predominantly protective role in radiation-induced cardiac function changes, may
      eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

PMID- 24331666
TI  - Phantom and clinical study of differences in cone beam computed tomographic
      registration when aligned to maximum and average intensity projection.
AB  - PURPOSE: To determine whether maximum or average intensity projection (MIP or
      AIP, respectively) reconstructed from 4-dimensional computed tomography (4DCT) is
      preferred for alignment to cone beam CT (CBCT) images in lung stereotactic body
      radiation therapy. METHODS AND MATERIALS: Stationary CT and 4DCT images were
      acquired with a target phantom at the center of motion and moving along the
      superior-inferior (SI) direction, respectively. Motion profiles were asymmetrical
      waveforms with amplitudes of 10, 15, and 20 mm and a 4-second cycle. Stationary
      CBCT and dynamic CBCT images were acquired in the same manner as stationary CT
      and 4DCT images. Stationary CBCT was aligned to stationary CT, and the couch
      position was used as the baseline. Dynamic CBCT was aligned to the MIP and AIP of
      corresponding amplitudes. Registration error was defined as the SI deviation of
      the couch position from the baseline. In 16 patients with isolated lung lesions,
      free-breathing CBCT (FBCBCT) was registered to AIP and MIP (64 sessions in
      total), and the difference in couch shifts was calculated. RESULTS: In the
      phantom study, registration errors were within 0.1 mm for AIP and 1.5 to 1.8 mm
      toward the inferior direction for MIP. In the patient study, the difference in
      the couch shifts (mean, range) was insignificant in the right-left (0.0 mm, <=1.0
      mm) and anterior-posterior (0.0 mm, <=2.1 mm) directions. In the SI direction,
      however, the couch position significantly shifted in the inferior direction after
      MIP registration compared with after AIP registration (mean, -0.6 mm; ranging 1.7
      mm to the superior side and 3.5 mm to the inferior side, P=.02). CONCLUSIONS: AIP
      is recommended as the reference image for registration to FBCBCT when target
      alignment is performed in the presence of asymmetrical respiratory motion,
      whereas MIP causes systematic target positioning error.

PMID- 24331665
TI  - Tumor tracking method based on a deformable 4D CT breathing motion model driven
      by an external surface surrogate.
AB  - PURPOSE: To develop a tumor tracking method based on a surrogate-driven motion
      model, which provides noninvasive dynamic localization of extracranial targets
      for the compensation of respiration-induced intrafraction motion in high
      precision radiation therapy. METHODS AND MATERIALS: The proposed approach is
      based on a patient-specific breathing motion model, derived a priori from 4
      dimensional planning computed tomography (CT) images. Model parameters
      (respiratory baseline, amplitude, and phase) are retrieved and updated at each
      treatment fraction according to in-room radiography acquisition and optical
      surface imaging. The baseline parameter is adapted to the interfraction
      variations obtained from the daily cone beam (CB) CT scan. The respiratory
      amplitude and phase are extracted from an external breathing surrogate, estimated
      from the displacement of the patient thoracoabdominal surface, acquired with a
      noninvasive surface imaging device. The developed method was tested on a database
      of 7 lung cancer patients, including the synchronized information on internal and
      external respiratory motion during a CBCT scan. RESULTS: About 30 seconds of
      simultaneous acquisition of CBCT and optical surface images were analyzed for
      each patient. The tumor trajectories identified in CBCT projections were used as
      reference and compared with the target trajectories estimated from surface
      displacement with the a priori motion model. The resulting absolute differences
      between the reference and estimated tumor motion along the 2 image dimensions
      ranged between 0.7 and 2.4 mm; the measured phase shifts did not exceed 7% of the
      breathing cycle length. CONCLUSIONS: We investigated a tumor tracking method that
      integrates breathing motion information provided by the 4-dimensional planning CT
      with surface imaging at the time of treatment, representing an alternative
      approach to point-based external-internal correlation models. Although an in-room
      radiograph-based assessment of the reliability of the motion model is envisaged,
      the developed technique does not involve the estimation and continuous update of
      correlation parameters, thus requiring a less intense use of invasive imaging.

PMID- 24331667
TI  - Comparison of different fractionation schedules toward a single fraction in high
      dose-rate brachytherapy as monotherapy for low-risk prostate cancer using 3
      dimensional radiobiological models.
AB  - PURPOSE: The aim of the present study was the investigation of different
      fractionation schemes to estimate their clinical impact. For this purpose, widely
      applied radiobiological models and dosimetric measures were used to associate
      their results with clinical findings. METHODS AND MATERIALS: The dose
      distributions of 12 clinical high-dose-rate brachytherapy implants for prostate
      were evaluated in relation to different fractionation schemes. The fractionation
      schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3
      fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of
      the different fractionation schemes was estimated through the complication-free
      tumor control probability (P+), the biologically effective uniform dose, and the
      generalized equivalent uniform dose index. RESULTS: For the different
      fractionation schemes, the tumor control probabilities were 98.5% in 1*20 Gy,
      98.6% in 2*14 Gy, 97.5% in 3*11 Gy, and 97.8% in 4*9.5 Gy. The corresponding P+
      values were 88.8% in 1*20 Gy, 83.9% in 2*14 Gy, 86.0% in 3*11 Gy, and 82.3% in
      4*9.5 Gy. With use of the fractionation scheme 4*9.5 Gy as reference, the
      isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were
      1*19.68 Gy, 2*13.75 Gy, and 3*11.05 Gy. The optimum fractionation schemes for 1,
      2, 3, and 4 fractions were 1*19.16 Gy with a P+ of 91.8%, 2*13.2 Gy with a P+ of
      89.6%, 3*10.6 Gy with a P+ of 88.4%, and 4*9.02 Gy with a P+ of 86.9%.
      CONCLUSIONS: Among the fractionation schemes 1*20 Gy, 2*14 Gy, 3*11 Gy, and 4*9.5
      Gy, the first scheme was more effective in terms of P+. After performance of a
      radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7
      Gy (average 19.5 Gy) should produce at least the same benefit as that given by
      the 4*9.5 Gy scheme, and it should reduce the expected total complication
      probability by approximately 40% to 55%.

PMID- 24331668
TI  - Alpha/beta ratio for normal lung tissue as estimated from lung cancer patients
      treated with stereotactic body and conventionally fractionated radiation therapy.
AB  - PURPOSE: To estimate the alpha/beta ratio for which the dose-dependent lung
      perfusion reductions for stereotactic body radiation therapy (SBRT) and
      conventionally fractionated radiation therapy (CFRT) are biologically equivalent.
      METHODS AND MATERIALS: The relations between local dose and perfusion reduction 4
      months after treatment in lung cancer patients treated with SBRT and CFRT were
      scaled according to the linear-quadratic model using alpha/beta ratios from 0 Gy
      to infinity Gy. To test for which alpha/beta ratio both treatments have equal
      biological effect, a 5-parameter logistic model was optimized for both dose
      effect relationships simultaneously. Beside the alpha/beta ratio, the other 4
      parameters were d50, the steepness parameter k, and 2 parameters (MSBRT and
      MCFRT) representing the maximal perfusion reduction at high doses for SBRT and
      CFRT, respectively. RESULTS: The optimal fitted model resulted in an alpha/beta
      ratio of 1.3 Gy (0.5-2.1 Gy), MSBRT=42.6% (40.4%-44.9%), MCFRT=66.9% (61.6%
      72.1%), d50=35.4 Gy (31.5-9.2 Gy), and k=2.0 (1.7-2.3). CONCLUSIONS: An equal
      reduction of lung perfusion in lung cancer was observed in SBRT and CFRT if local
      doses were converted by the linear-quadratic model with an alpha/beta ratio equal
      to 1.3 Gy (0.5-2.1 Gy).

PMID- 24331669
TI  - Audio-visual biofeedback does not improve the reliability of target delineation
      using maximum intensity projection in 4-dimensional computed tomography radiation
      therapy planning.
AB  - PURPOSE: To investigate whether coaching patients' breathing would improve the
      match between ITVMIP (internal target volume generated by contouring in the
      maximum intensity projection scan) and ITV10 (generated by combining the gross
      tumor volumes contoured in 10 phases of a 4-dimensional CT [4DCT] scan). METHODS
      AND MATERIALS: Eight patients with a thoracic tumor and 5 patients with an
      abdominal tumor were included in an institutional review board-approved
      prospective study. Patients underwent 3 4DCT scans with: (1) free breathing (FB);
      (2) coaching using audio-visual (AV) biofeedback via the Real-Time Position
      Management system; and (3) coaching via a spirometer system (Active Breathing
      Coordinator or ABC). One physician contoured all scans to generate the ITV10 and
      ITVMIP. The match between ITVMIP and ITV10 was quantitatively assessed with
      volume ratio, centroid distance, root mean squared distance, and overlap/Dice
      coefficient. We investigated whether coaching (AV or ABC) or uniform expansions
      (1, 2, 3, or 5 mm) of ITVMIP improved the match. RESULTS: Although both AV and
      ABC coaching techniques improved frequency reproducibility and ABC improved
      displacement regularity, neither improved the match between ITVMIP and ITV10 over
      FB. On average, ITVMIP underestimated ITV10 by 19%, 19%, and 21%, with centroid
      distance of 1.9, 2.3, and 1.7 mm and Dice coefficient of 0.87, 0.86, and 0.88 for
      FB, AV, and ABC, respectively. Separate analyses indicated a better match for
      lung cancers or tumors not adjacent to high-intensity tissues. Uniform expansions
      of ITVMIP did not correct for the mismatch between ITVMIP and ITV10. CONCLUSIONS:
      In this pilot study, audio-visual biofeedback did not improve the match between
      ITVMIP and ITV10. In general, ITVMIP should be limited to lung cancers, and
      modification of ITVMIP in each phase of the 4DCT data set is recommended.

PMID- 24331670
TI  - We need better figures!

PMID- 24331671
TI  - Prognostic utility of cell cycle progession score in men with prostate cancer
      after primary external beam radiation therapy. In regard to Freedland et al.

PMID- 24331672
TI  - Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic
      cancer. In Regard to Kelly et al.

PMID- 24331673
TI  - In reply to Bahl et al.

PMID- 24331674
TI  - In reply to Berlin et al.

PMID- 24331675
TI  - Factors that determine academic versus private practice career interest in
      radiation oncology residents in the United States: results of a nationwide
      survey. In regard to Chang et al.

PMID- 24331676
TI  - In reply to Leung.

PMID- 24331677
TI  - Neuroendocrine control of feeding behavior and psychomotor activity by pituitary
      adenylate cyclase-activating polypeptide (PACAP) in vertebrates.
AB  - Food intake is a fundamental for animals to surviving and keeping offspring. The
      hypothalamic region of the brain and the brain stem in vertebrates are a center
      that plays an important role in the control of feeding and its related behaviors
      including locomotor and psychomotor activities. Pituitary adenylate cyclase
      activating polypeptide (PACAP) has firstly been identified as a hypophysiotropic
      hormone involved in adenohypophyseal hormone release, and subsequently has been
      considered as a neuropeptide exerting multifunctional roles in the central and
      peripheral nervous systems and several tissues in vertebrates. For example, PACAP
      is involved in the neuroendocrine control of food intake and acts as an
      anorexigenic peptide to regulate satiety. Recent works on animal models such as
      rodents and goldfish which are both excellent animal models for investigating the
      neuroendocrinological roles of PACAP have been extensively examined and
      considerable information has been accumulated. In addition, psychophysiological
      effects of PACAP on emotional behavior have recently been found. Therefore, this
      review article provides an overview of the neuroendocrine regulation of feeding
      behavior and psyphysiological activity by PACAP in vertebrates.

PMID- 24331678
TI  - Relative shrinkage of adipocytes by paraffin in proportion to plastic embedding
      in human adipose tissue before and after weight loss.
AB  - Adipocyte size is a major modulator of endocrine functioning of adipose tissue
      and methods allowing accurate determination of adipocyte size are important to
      study energy metabolism. The aim of this study was to assess the relative
      shrinkage of adipocytes before and after weight loss by comparing adipose tissue
      from the same subjects embedded in paraffin and plastic. 18 healthy subjects (5
      males and 13 females) aged 20-50 y with a BMI of 28-38 kg/m2 followed a very low
      energy diet for 8 weeks. Adipose tissue biopsies were taken prior to and after
      weight loss and were processed for paraffin and plastic sections. Parameters of
      adipocyte size were determined with computer image analysis. Mean adipocyte size
      was smaller in paraffin compared to plastic embedded tissue both before (66 +/- 4
      vs. 103 +/- 5 MUm, P < 0.001) as after weight loss (62 +/- 4 vs. 91 +/- 5 MUm, P
      < 0.001). Relative shrinkage of adipocytes in paraffin embedded tissue in
      proportion to plastic embedded tissue was not significantly different before and
      after weight loss (73 and 69%, respectively). Shrinkage due to the type of
      embedding of the adipose tissue can be ignored when comparing before and after
      weight loss. Plastic embedding of adipose tissue provides more accurate and
      sensitive results.

PMID- 24331679
TI  - Variant rs1421085 in the FTO gene contribute childhood obesity in Chinese
      children aged 3-6 years.
AB  - OBJECTIVE: Childhood obesity has become a public health crisis worldwide due to
      an alarming increase in its prevalence. Numerous studies have demonstrated that
      the common variants (rs1421085 and rs17817449) of the fat mass and obesity
      associated (FTO) gene are associated with the obesity in adult and children in
      European. However, these two variants of FTO gene in childhood obesity have not
      been established in Chinese populations. METHODS: In this population-based case
      control study, 158 obese preschooler and 397 normal population controls aged 3-6
      years were recruited between June 2007 and April 2008 from 6 kindergartens of
      Huai-an city in Jiangsu Province, China. All the children were conducted the body
      examinations and provided blood sample to detect the serum lipid levels and FTO
      rs1421085 T>C and rs17817449 T>G genetic variances. RESULTS: In the association
      analysis between the FTO gene variant and risk of childhood obesity, compared
      with the rs1421085TT wide-type genotype, rs1421085 CC and CT/CC genotypes were
      associated with 59% and 71% increased risks of childhood obesity (adjusted OR =
      1.59, 95%CI = 1.00-2.53 for CC; adjusted OR = 1.71, 95%CI = 1.10-2.65 for CT/CC),
      while the rs17817449 T > G variant was not associated with the significantly
      increased risk of childhood obesity. In addition, the higher level of serum TG
      (>0.64 mmol/l) was associated with 93% increased risk of childhood obesity
      (adjusted OR = 1.93, 95%CI = 1.30-2.87), and the higher serum HDL-C level (>1.14
      mmol/l) was associated with 45% decreased risk of childhood obesity (adjusted OR
      = 0.55, 95%CI = 0.37-0.81). But the quantitative phenotypes analysis regarding
      the levels of TC, TG, HDL-C, and LDL-C were not found to be significantly
      associated with the variants of rs1421085 and rs17817449 both in the cases and
      controls. CONCLUSION: The FTO rs1421085 T>C polymorphism may modulate the
      magnitude of dyslipidemia in Chinese early-onset obesity.

PMID- 24331680
TI  - Physiological and behavioural outcomes of a randomised controlled trial of a
      cognitive behavioural lifestyle intervention for overweight and obese
      adolescents.
AB  - AIM: This study evaluates the efficacy of the Choose Health program, a family
      based cognitive behavioural lifestyle program targeting improved eating and
      activity habits, in improving body composition, cardiovascular fitness, eating
      and activity behaviours in overweight and obese adolescents. METHOD: The sample
      comprised 29 male and 34 female overweight (n = 15) or obese (n = 48) adolescents
      aged 11.5-18.9 years (M = 14.3, SD = 1.9). Participants were randomly allocated
      to treatment or waitlist control conditions; waitlist condition participants were
      offered treatment after 6 months. DEXA-derived and anthropometric measures of
      body composition; laboratory-based cycle ergometer and field-assessed
      cardiovascular fitness data; objective and self-report physical activity
      measures; and self-report measures of eating habits and 7-day weighed food
      diaries were used to assess treatment outcome. Adherence to treatment protocols
      was high. RESULTS: Treatment resulted in significant (p < .05) and sustained
      improvements in a range of body composition (body fat, percent body fat, lean
      mass) and anthropometric measures (weight, BMI, BMI-for-age z-score and
      percentiles). Minimal improvements were seen in cardiovascular fitness. Similar
      results were obtained in completer and intention-to-treat analysis. Poor
      adherence to assessment protocols limits conclusions that can be drawn from
      physical activity and dietary data. CONCLUSIONS: Participation in the Choose
      Health program resulted in significant improvement in body composition. Longer
      term follow up is required to determine the durability of intervention effects.
      Alternative approaches to the measurement of diet and physical activity may be
      required for adolescents.

PMID- 24331681
TI  - The effects of partial use of formula diet on weight reduction and metabolic
      variables in obese type 2 diabetic patients--multicenter trial.
AB  - AIMS: To clarify the usefulness of protein-sparing modified formula diet in obese
      type 2 diabetic patients, the effects of partial use of formula diet on weight
      reduction and changes in related metabolic variables, and the improving rates of
      risk factors per 1% body weight reduction, were compared with those of
      conventional subcaloric diet. SUBJECTS AND METHODS: Obese patients [BMI >25
      kg/m2] with diabetic mellitus were randomly assigned to a low-caloric diet with
      partial use of formula diet group (FD, n = 119) and a conventional low-caloric
      diet group (CD, n = 110). Subjects in FD took one pack of formula diet
      (MicroDiet(r), 240 kcal/pack) in place of one of three daily low-caloric meals
      for 24 weeks. Total daily calorie prescribed was same. RESULT: Weight reduction
      was greater in FD than in CD (week 24: -3.5 vs -1.4 kg; all p < 0.001). Systolic
      blood pressure decreased significantly only in FD. HbA1c reduction was greater in
      FD than in CD. HDL-cholesterol increased significantly more in FD than in CD
      (week 24: +2.8 vs. +0.6 mg/dl, p < 0.001). Among several improving rates (%) of
      risk factors/1% body weight reduction, those of HbA1c at weeks 16 and 24,
      triglyceride at week 8 and HDL-cholesterol at week 24, were significantly higher
      in FD than CD. Doses of sulfonylurea and thiazolidinedione were significantly
      decreased in FD than in CD. CONCLUSION: Partial use of formula diet was much more
      effective in reducing body weight, and also in improving coronary risk factors
      than conventional diet in part due to reduced body weight through decreased
      energy diet intake and due to dietary composition of the formula diet.

PMID- 24331682
TI  - Comparison of anthropometric and body composition measures as predictors of
      components of the metabolic syndrome in a clinical setting.
AB  - PROBLEM: The use of body mass index (BMI) to assess obesity and health risks has
      been criticized in scientific and lay publications because of its failure to
      account for body shape and inability to distinguish fat mass from lean mass. We
      sought to determine whether other anthropometric measures (waist circumference
      (WC), waist-to-height ratio (WtH), percent body fat (%BF), fat mass index (FMI),
      or fat-free mass index (FFMI)) were consistently better predictors of components
      of the metabolic syndrome than BMI is. METHODS: Cross-sectional measurements of
      height, weight, waist circumference and percent body fat were obtained from
      12,294 adults who took part in annual physical exams provided by EHE
      International, Inc. Blood pressure was measured during the exam and HDL, LDL, and
      fasting glucose were measured from blood samples. Pearson correlations, linear
      regression, and adjusted Receiver Operator Characteristic (ROC) curves were used
      to relate each anthropometric measure to each metabolic risk factor. RESULTS:
      None of the measures was consistently the strongest predictor. BMI was the
      strongest predictor of blood pressure, measures related to central adiposity (WC
      and WtH) performed better at predicting fasting glucose, and all measures were
      roughly comparable at predicting cholesterol levels. In all, differences in areas
      under ROC curves were 0.03 or less for all measure/outcome pairs that performed
      better than BMI. CONCLUSION: Body mass index is an adequate measure of adiposity
      for clinical purposes. In the context of lay press critiques of BMI and
      recommendations for alternative body-size measures, these data support clinicians
      making recommendations to patients based on BMI measurements.

PMID- 24331683
TI  - Association between obesity and various parameters of physical fitness in Korean
      students.
AB  - The purpose of this study was to evaluate the association between the types of
      obesity classified according to the body mass index (BMI) and/or waist
      circumference (WC) and the various parameters of physical fitness in Korean
      college students. BMI, WC, and fitness assessments were performed on 726 male
      college student volunteers who visited a public health center in Seoul, Korea.
      Classification based on BMI and/or WC was established according to the data in
      the WHO's Asia-Pacific standard report, and the subjects were divided into the
      following 4 groups: (1) obese as determined by BMI, but not WC (BMI Obesity
      Group, BOG); (2) obese as determined by WC, but not BMI (WC Obesity Group, WOG);
      (3) obese as determined by both BMI and WC (BWOG); and (4) non-obese normal group
      (NG). Fitness assessment parameters such as cardiorespiratory endurance,
      cardiovascular function, muscular endurance, muscular strength, flexibility,
      power, agility, and balance were evaluated through the following measurements:
      time required to run 1.5 km, physical efficiency index (PEI), vital capacity (l),
      push-ups (reps/2 min), sit-ups (reps/2 min), back strength (kg), grip strength
      (kg), sit and reach distance (cm), vertical jumps (cm), whole body reaction time
      (ms), side steps (reps/30 s), and maximum time of standing on 1 foot with closed
      eyes (s). The odds ratios (OR) (95% confidence interval [CI]) of the BOG and WOG
      for the 1.5-km run were 0.367 (0.192-0.701) and 0.168 (0.037-0.773),
      respectively; of the BWOG and WOG for vital capacity were 5.900 (1.298-26.827)
      and 5.364 (1.166-24.670), respectively; of the BOG for push-ups was 0.517 (0.279
      0.959); of the WOG for back strength was 0.206 (0.045-0.945); of the BWOG and BOG
      for grip strength were 5.973 (1.314-27.157) and 2.036 (1.089-3.807),
      respectively; and of the BOG for the whole body reaction time was 0.405 (0.212
      0.774), as compared to the NG. We conclude that all 3 types of obesity
      (classified into the BWOG, BOG, and WOG) result in reduced cardiorespiratory and
      muscular endurance, but increased muscular strength and vital capacity.

PMID- 24331684
TI  - Serum leptin concentrations in Mongolian women.
AB  - OBJECTIVE: The aim of our study is to elucidate the association between leptin
      and obesity in Mongolian women. METHOD: Total 181 women participated in the study
      including 118 Mongolians and 63 Han. Body mass index (BMI) was calculated by
      weight (kg) divided by square height (m2). Percent body fat (%fat) was detected
      by bioelectrical impedance analysis (BIA). Fasting serum leptin was determined by
      ELISA. RESULT: The average BMI and %fat of Mongolian and Han women was 25.14 +/-
      4.48 kg/m2, 24.30 +/- 3.62 kg/m2 and 36.10 +/- 6.23%, 33.84 +/- 5.98%,
      respectively. Fasting serum leptin level in obese women (BMI >= 25) was
      remarkably higher than in normal weight women (18.5 < BMI < 25) in Mongolian and
      Han ethnic groups (all P < 0.001). Fasting serum leptin level in Mongolian women
      had borderline significance compared with it in Han women (P = 0.049). Multiple
      linear regression models revealed that ethnicity, %fat and BMI were associated
      with serum leptin concentrations independent of age. CONCLUSION: In Mongolian and
      Han women, fasting serum leptin level was positively associated with BMI and %fat
      (all P < 0.001).

PMID- 24331685
TI  - Weight loss improves serum mediators and metabolic syndrome features in android
      obese subjects.
AB  - Serum anti-/pro-inflammatory molecules such as adiponectin, IL-6, IL-10, and TNF
      alpha, and metabolic syndrome (Met Syn) features in 15 android obese (6 Met Syn
      and 9 non-Met Syn) subjects were assessed during an 8-week weight control
      program. The results showed that the body mass index, weight, lean body mass,
      triglyceride, total cholesterol/high density lipoprotein cholesterol ratio, and
      TNF-alpha in Met Syn subjects were significantly (P < 0.05) improved. This study
      suggests that weight reduction in android obese subjects may be beneficial in
      reducing cardiovascular diseases via improving serum IL-6 and TNF-alpha levels,
      as well as Met Syn features.

PMID- 24331686
TI  - Infants born to mothers with gestational diabetes mellitus: mild neonatal
      effects, a long-term threat to global health.

PMID- 24331687
TI  - Orbital compression syndrome in a child with sickle cell disease.

PMID- 24331688
TI  - Serial neutrophil values facilitate predicting the absence of neonatal early
      onset sepsis.
AB  - OBJECTIVE: To validate established neonatal neutrophil reference ranges (RRs) and
      determine the utility of serial measurements of neutrophil values in the first 24
      hours to predict the absence of neonatal early-onset sepsis (EOS). STUDY DESIGN:
      Retrospective study of 2073 admissions to the neonatal intensive care unit (2009
      2011). Neonates were classified as blood culture-positive, proven EOS (n = 9),
      blood culture-negative but clinically suspect EOS (n = 292), and not infected (n
      = 1292). Neutrophil values from 745 not-infected neonates without perinatal
      complications were selected to validate RR distributions. Positive and negative
      predictive values were calculated; area under receiver operating characteristic
      curves (AUCs) were constructed to predict the presence or absence of EOS.
      Neutrophil value scores were established to determine whether serial neutrophil
      values predict the absence of EOS. RESULTS: Seventy-seven percent of admissions
      to the neonatal intensive care unit were evaluated for EOS: 9 (0.56%) had proven
      EOS with positive blood culture <= 37 hours; 18% had clinically suspect EOS.
      Neutropenia occurred in preterm neonates, and nonspecific neutrophilia was common
      in uninfected neonates. The distribution of neutrophil values differed
      significantly between study groups. The specificity for absolute total immature
      neutrophils and immature to total neutrophil proportions was 91% and 94%,
      respectively, with negative predictive value of 99% for proven and 78% for proven
      plus suspect EOS. Absolute total immature neutrophils and immature to total
      neutrophil proportions had the best predictability for EOS >6 hours postnatal
      with an AUC ~ 0.8. Neutrophil value scores predicted the absence of EOS with AUC
      of 0.9 and 0.81 for proven and proven plus suspect EOS, respectively. CONCLUSION:
      Age-dependent neutrophil RRs remain valid. Serial neutrophil values at 0, 12, and
      24 hours plus blood culture and clinical evaluation can be used to discontinue
      antimicrobial therapy at 36-48 hours.

PMID- 24331689
TI  - Metabolic bone disease and bone mineral density in very preterm infants.
AB  - OBJECTIVES: To evaluate bone mineral density (BMD) in preterm neonates at
      discharge and identify the optimum cutoff values for serum alkaline phosphatase
      (ALP) and phosphorus (P) concentrations to diagnose the severity of metabolic
      bone disease of prematurity. STUDY DESIGN: A total of 336 preterm neonates (<= 31
      weeks' gestation and birth weight <= 1500 g) were prospectively evaluated for BMD
      before discharge using dual-energy X-ray absorptiometry. RESULTS: BMD reference
      values (at ALP <= 500 IU/L) were measured in 279 patients. BMD was classified as
      poor (<10th percentile) at <0.068 g/cm(2), fair (10th-25th percentile) at 0.068
      0.081 g/cm(2), good (25th-75th percentile) at 0.081-0.112 g/cm(2), and very good
      (>75th percentile) at >0.112 g/cm(2). Increased BMD was associated with a higher
      birth weight, short duration of parenteral nutrition, and the absence of small
      for gestational age status, patent ductus arteriosus, intraventricular
      hemorrhage, and other clinical variables. Metabolic bone disease of prematurity
      was absent (ALP <= 500 IU/L) in 279 cases (83.0%), mild (ALP >500 IU/L and P >=
      4.5 mg/dL) in 46 cases (13.7%), and severe (ALP >500 IU/L and P <4.5 mg/dL) in 11
      cases (3.3%). CONCLUSIONS: A BMD >0.068 g/cm(2) at discharge indicated a 90.3%
      probability of not developing metabolic bone disease of prematurity. The factors
      independently associated with increased BMD included higher birth weight, short
      duration of parenteral nutrition, absence of intraventricular hemorrhage,
      exclusive feeding of fortified breast milk, and older age at discharge.

PMID- 24331690
TI  - [Antiviral nucleotide-induced dynamic change of HBV DNA and HBsAg and
      significance of quarterly and annual quantitative measurements over 5-year follow
      up of chronic hepatitis B patients].
AB  - OBJECTIVE: To analyze the dynamic changes in hepatitis B virus (HBV) DNA and
      hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B (CHB) patients
      following treatment by antiviral nucleotide drugs over a 5-year follow-up period
      and to assess the clinical significance of quarterly and annual quantitative
      measurements. METHODS: One-hundred-and-ten patients with CHB were enrolled in the
      study and administered on-going standard mono-therapy with various antiviral
      nucleotide drugs. Over a 5-year period, the HBV DNA level was measured by
      quantitative PCR every three months and the HBsAg levels were measured by
      chemiluminescence once a year. The dynamic changes in HBV DNA and HBsAg levels
      were assessed by Chi-squared test and ANOVA. RESULTS: Only 90 of the CHB patients
      completed the 5-year follow-up and were included in the analysis. The patients
      who showed HBeAg-positivity at baseline (study start) had higher levels of HBV
      DNA and HBsAg than the patients showing HBeAg-negativity. In general, the
      antiviral nucleotide drug therapy induced downward trends in HBsAg and HBV DNA
      level over time (F = 17.1, 151.53, all P less than 0.05). However, the most
      robust reduction in HBV DNA occurred during the first year. The HBsAg level
      followed an opposite trend, with the most robust reductions occurring in the 3rd,
      4th and 5th years of treatment. CONCLUSION: Long-term antiviral nucleotide mono
      therapies induced decreases in HBV DNA and HBsAg levels in CHB patients, with the
      former being most reduced in the short-term and the latter in the long-term.

PMID- 24331691
TI  - [Clinical characteristics of and factors related to relapse in chronic hepatitis
      B patients after nucleoside analogues withdrawal].
AB  - OBJECTIVE: To investigate the clinical characteristics of and factors related to
      relapse in chronic hepatitis B (CHB) patients who had previously achieved
      cessation criteria and had been withdrawn from nucleoside analogues treatment.
      METHODS: Sixty CHB patients who experienced relapse after nucleoside analogues
      withdrawal based on cessation criteria were enrolled in the study
      retrospectively. Each patient's data on biochemical, serological and viral
      characteristics corresponding to baseline (treatment initiation), withdrawal and
      relapse were collected. COX proportional hazard modeling was used to evaluate the
      factors related to relapse. RESULTS: The hepatitis B e antigen (HBeAg)-positive
      and -negative patients had similar median antiviral treatment times (38 months
      (range: 24 - 80) vs. 35 months (30 - 60); Z = -1.313, P more than 0.05). For all
      patients, the median follow-up time was 12 months (2 - 72), during which 49
      (81.7%) patients developed virological breakthrough and 17 (28.3%) developed
      HBeAg recurrence. The patients who experienced virological breakthrough or HBeAg
      recurrence had significantly higher baseline levels of HBV DNA than those
      patients who remained disease-free (t = 2.15 and -2.54 respectively; P less than
      0.05). The median relapse time of the HBeAg-positive patients was significantly
      longer than that of the HBeAg-negative patients (14 months (3 - 72) vs. 6 months
      (3 - 36); Chi-square test = 7.045, P less than 0.01). HBeAg status at baseline
      was identified as an independent factor associated with relapse (relative risk =
      1.937, 95% confidence interval = 1.14-3.28, P less than 0.05). CONCLUSION: HBeAg
      positive and-negative patients showed distinct clinical characteristics of
      relapse, with the latter being more prone to relapse soon after nucleoside
      analogues withdrawal. Prolonging the treatment course may be beneficial to HBeAg
      negative patients, even if cessation criteria are achieved.

PMID- 24331692
TI  - [Differential response to pegylated interferon plus ribavirin combination therapy
      in chronic hepatitis C and HIV/HCV co-infected patients].
AB  - OBJECTIVE: To investigate the potential differences in response to pegylated
      interferon (Peg-IFN) plus ribavirin (RBV) combination therapy in patients with
      hepatitis C virus (HCV) mono-infection and human immunodeficiency virus (HIV)/HCV
      co-infection. METHODS: Seventy HIV/HCV patients and sixty HCV patients, were
      administered a 48-week course of Peg-IFN + RBV. The HCV load was tested by the
      COBAS automatic viral load analysis system (lower limit of quantification = 15
      IU/ml) at treatment weeks 0 (baseline), 4, 12, 24, and 48 and at week 24 after
      drug withdrawal. The patients were also genotyped by sequencing for the host
      encoded interleukin (IL)-28B single nucleotide polymorphisms (SNPs) related to
      HCV Peg-IFN + RBV therapy outcome: rs8099917, rs12979860 and rs12980275. In
      addition, the HCV-encoded NS5B gene region was genotyped by nested-PCR and
      sequencing followed by BLAST searching of the Los Alamos National Laboratory HCV
      database. The significance of between-group differences in response to therapy
      and roles of SNPs were evaluated by statistical analyses. RESULTS: The ratio of
      sustained virological response (SVR) was significantly lower in the HIV/HCV co
      infected patients than the HCV mono-infected patients (32.9% vs. 71.7%; P less
      than 0.001). While the HIV/HCV co-infected patients did not show a significant
      difference in SVR ratio achieved between individuals infected with the HCV-1
      genotype and the non-HCV-1 genotype (30.8% vs. 33.3%; P = 1.000), the HCV mono
      infected patients did (86.1% vs. non 50.0%, P = 0.002). Moreover, the SVR ratio
      was higher in the HCV-1 genotype HCV mono-infected patients than in the HIV/HCV-1
      genotype co-infected patents (30.8% vs. 86.1%; P less than 0.001). The different
      IL-28B genotypes were not significantly correlated to the PEG-IFN+RBV therapy
      response of either HCV mono-infected patients or HIV/HCV co-infected patients (P
      more than 0.05). CONCLUSION: HCV mono-infected patients respond better to Peg-IFN
      + RBV therapy than HIV/HCV co-infected patients. The HCV-1 genotype may promote
      this therapy response in HCV mono-infected patients, but the IL-28B genotypes
      appear to play no significant role.

PMID- 24331693
TI  - [Inhibition of silent information regulator-1 in hepatocytes induces lipid
      metabolism disorders and enhances hepatitis C virus replication].
AB  - OBJECTIVE: To investigate the role of the host-encoded silent information
      regulator 1 (SIRT1) on hepatocytes' lipid metabolism under conditions of
      hepatitis C virus (HCV) infection and assess its potential effects on virus
      replication in vitro. METHODS: The Huh-7.5 human hepatocyte cell line was used as
      the control group and Huh-7.5 cells stably expressing the HCV replicon (Huh7.5
      HCV) were used as the experimental group. Effects of interferon (IFN) treatment
      and activation of SIRT1 by resveratrol were also observed. The mRNA and protein
      expression levels of SIRT1 were detected by real time (q)PCR and western
      blotting. Effects on SIRT1 protein activity were tested by measuring the levels
      of reactive oxygen species (ROS) and the nicotinamide adenine dinucleotide
      (NAD+)/beta-nicotinamide adenine dinucleotide, reduced (NADH) by flow cytometry
      and chromatometry, and the levels of triacylglycerol (TG), total cholesterol
      (TC), and fatty acid beta oxidation rate by enzymatic analysis and liquid
      scintillation counting. Effects on mRNA expression of SIRT1 downstream lipid
      metabolism genes were measured by qPCR. RESULTS: The Huh7.5-HCV cells had a
      significantly higher level of ROS (3.8+/-0.5 vs. Huh-7.5: 1.0+/-0.2; t = 12.736,
      P less than 0.01) but significantly lower levels of NAD+/NADH (0.03+/-0.01 vs.
      0.12+/-0.03; t = 6.971, P less than 0.01), SIRT1 activity (0.3+/-0.1 vs. 1.0+/
      0.2, 0.9+/-0.2, F = 6.766, P less than 0.01), SIRT1 mRNA (0.4+/-0.1 vs. 1.0+/
      0.3, 0.9+/-0.2, F = 5.864, P less than 0.01), and SIRT1 protein (0.3+/-0.1 vs.
      0.8+/-0.2, 0.9+/-0.2, F = 5.419, P less than 0.01). The lower levels of SIRT1 in
      Huh7.5-HCV cells accompanied decreased phosphorylation of the forkhead box O1
      (FoxO1), which not only up-regulated the downstream genes of SREBP-1c, FAS, ACC,
      SREBP-2, HMGR and HMGS (which increased fatty acid synthesis) but also down
      regulated the downstream genes of PPAR and CPT1A genes (which decreased fatty
      acid beta oxidation). IFN treatment restored all of the aforementioned changes.
      Resveratrol-induced SIRT activation improved the perturbations in lipid
      metabolism pathways, as evidenced by an increase in fatty acid beta oxidation and
      a decrease in TG and TC synthesis, as well as inhibited HCV replication.
      CONCLUSION: HCV may decrease the NAD+/NADH ratio in hepatocytes, leading to a
      down-regulation of SIRT1 activity and expression and perturbing the downstream
      expression profile of lipid metabolism-related factors, ultimately causing lipid
      metabolism disorders and establishing a permissive intracellular environment for
      HCV replication.

PMID- 24331694
TI  - [Non-invasive assessment of portal hypertension in patients with liver cirrhosis
      using FibroScan transient elastography].
AB  - OBJECTIVE: To investigate the clinical value of FibroScan transient elastography
      for assessing portal hypertension in liver cirrhosis patients by determining the
      relationship between the liver or spleen stiffness measurement with the imaging
      parameters of esophageal varices, portal vein width, spleen volume, and splenic
      vein width. METHODS: A total of 259 patients with liver cirrhosis underwent
      FibroScan measurement, ultrasound, computed tomography and routine blood
      analyses. One-hundred-and-one of those patients also underwent endoscopy to
      diagnose esophageal varices. Receiver operating characteristic (ROC) curves were
      generated and the areas under the curves (AUCs) were calculated to assess the
      accuracy of the FibroScan liver and spleen stiffness measurements to predict
      esophageal varices. Pearson's correlation analysis was used to assess the
      relationship between clinical features. RESULTS: The median liver and spleen
      stiffness of the cirrhotic patients were 24.27 kPa and 44.64 kPa, respectively.
      Liver and spleen stiffness increased in conjunction with increases in Child-Pugh
      score. Liver stiffness was positively correlated with spleen stiffness (P less
      than 0.05). Liver and spleen stiffness were positively correlated with esophageal
      varices, portal vein width, spleen thickness, spleen volume, and splenic vein
      width. The correlation of spleen stiffness was higher than that of liver
      stiffness. Spleen stiffness was also negatively correlated with white blood cell
      count and platelet count. Liver and spleen stiffness also increased in
      conjunction with increased severity of esophageal varices. The AUC of spleen
      stiffness was higher than that of liver stiffness for predicting esophageal
      varices (0.804 vs. 0.737). The optimal cut-off level of spleen stiffness was 44.5
      kPa (sensitivity: 88%; specificity: 68%). The estimated prevalence of esophageal
      varices was 97.87% and the optimized cut-off level of liver stiffness was 18.0
      kPa. CONCLUSION: FibroScan appears to be a clinically valuable non-invasive
      method to assess portal hypertension in cirrhotic patients. Both liver and spleen
      stiffness measurements correlated with portal hypertension but the spleen
      stiffness measurement may be of higher clinical value.

PMID- 24331695
TI  - [Anti-proliferation effect of sorafenib in combination with 5-FU for
      hepatocellular carcinoma in vitro: antagonistic performance and mechanism].
AB  - OBJECTIVE: To investigate the anti-cancer efficacy and mechanism of sorafenib and
      5-fluorouracil (5-FU) therapy in vitro using the HCC cell line MHCCLM3. METHODS:
      The effects of sorafenib and 5-FU, alone or in combination, on the proliferation
      of MHCCLM3 cells were evaluated by cell viability assays. Combined-effects
      analyses were conducted according to the median-effect principle established by
      Chou and Talalay. Effects on cell cycle distributions were tested by flow
      cytometry and expression of proteins related to the RAF/MEK/ERK and STAT3
      signaling pathways and cyclinD1 were tested by western blotting. RESULTS:
      Sorafenib and 5-FU alone or in combination displayed significant efficacy in
      inhibiting proliferation of the MHCCLM3 cells, with the following inhibition
      rates: sorafenib: 46.16% +/- 2.52%, 5-FU: 28.67% +/- 6.16%, and sorafenib + 5-FU:
      22.59% +/- 6.89%. The sorafenib + 5-FU combination did not provide better results
      than treatment with either drug alone. The combination index values of the
      sorafenib and 5-FU treatments were mainly greater than 1, indicating that the two
      agents induced antagonistic, instead of synergistic, effects on the MHCCLM3
      cells. In addition, the MHCCLM3 cells were less sensitive to 5-FU when
      administrated in combination with sorafenib, as evidenced by the half inhibitory
      concentration (IC50) significantly increasing from (102.86 +/- 27.84) mg/L to
      (178.61 +/- 20.73) mg/L (P = 0.003). Sorafenib alone induced G1 phase arrest
      (increasing from 44.73% +/- 1.63% to 65.80% +/- 0.56%; P less than 0.001) and
      significantly decreased the proportion of cells in S phase (decreasing from
      46.63% +/- 0.65% to 22.83% +/- 1.75%; P less than 0.01), as well as down
      regulated cyclinD1 expression (0.57 +/- 0.03-fold change vs. untreated control
      group; P less than 0.01). 5-FU alone up-regulated cyclinD1 expression (1.45 +/-
      0.12-fold change vs. untreated control group; P less than 0.01). Moreover,
      sorafenib alone significantly inhibited the RAF/MEK/ERK and STAT3 pathways, with
      the fold-changes of p-C-RAF, p-ERK1/2 and p-STAT3 being 0.56 +/- 0.05, 0.54 +/-
      0.02 and 0.36 +/- 0.02, respectively (all P less than 0.01); 5-FU alone produced
      no significant effects on these pathways. CONCLUSION: Administered alone, both
      sorafenib and 5-FU exert anti-tumoral activity on in vitro cultured HCC cells.
      The sorafenib + 5-FU combination treatment produces antagonistic, rather than
      synergistic, effects. Sorafenib-inhibited RAF/MEK/ERK and STAT3 signaling and
      cyclinD1 expression may have induced the observed G1phase arrest and S phase
      reduction, thereby reducing the cells' sensitivity to 5-FU.

PMID- 24331696
TI  - [Study on clinical features and etiology of primary Budd-Chiari Syndrome].
AB  - OBJECTIVE: To prospectively study clinical features and etiology in patients with
      incident Budd-Chiari syndrome (BCS) in China. METHODS: Taking consecutive case
      series of patients with incident BCS as who were diagnosed in our hospital,
      enrolled from September 2010 to January 2012 as the object of research, and the
      follow-up was lasting until June 2012. Taking records for all patients' symptoms,
      signs, laboratory findings, radiology findings, treatment, interventional
      treatment survival and symptom-free period. RESULTS: There are total 149 incident
      cases of BCS. In which, the median age was 46 years old (range 10 to 82); 61.7%
      of them were male patients, 38.3% were female patients; 85.9% of them were
      chronic, the other patients (14.1%) were diagnosed during acute or subacute
      periods; the median duration of symptoms before diagnosis was 96 months (range 1
      day to 360 months). In terms of causes, 30.9% of the patients caused by hepatic
      venous block, 5.4% of them resulted from inferior vena cava block, and the rest
      63.8% were suffered from combined hepatic venous and inferior vena cava block.
      80.5% patients have at least one etiological factor, Furthermore, the most common
      cause was the web (61.1%), only 4.8% have myeloproliferative diseases (JAK2 V617F
      mutation), and none Factor V Leiden mutation cases was found. 144 patients were
      treated by percutaneous transluminal angioplasty, the technical success rate was
      95.1%, and took oral anticoagulation therapy for 12 months. At 18 months, The
      survival rate and the symptom-free survival rate after percutaneous transluminal
      angioplasty were 97.8% and respectively. CONCLUSION: Web is the most prevalent
      etiological factor for BCS in China. It is different in western countries; the
      common reasons of BCS are risk factors related to thrombosis, such as
      myeloproliferative disease and Factor V Leiden mutation, etc., which are seldom
      found in Chinese BCS patients. In China, most chronic BCS patients were treated
      with percutaneous transluminal angioplasty and have excellent clinical outcome.

PMID- 24331697
TI  - [Intrahepatic portosystemic shunt assisted by percutaneous transhepatic approach
      for treatment of portal vein thrombosis].
AB  - OBJECTIVE: To retrospectively analyze the safety and efficacy of mechanical
      thrombectomy combined with pharmacologic thrombolysis to treat non-acute and
      symptomatic portal vein thrombosis (PVT) using an intrahepatic portosystemic
      shunt (IPS) assisted by percutaneous transhepatic approach. METHODS: From April
      2006 to May 2012, 18 patients with non-acute and symptomatic PVT were treated
      with balloon dilation, sheath-directed thrombus aspiration and continuous
      infusion of urokinase using the IPS assisted by percutaneous transhepatic
      approach. The significance of differences in the portosystemic gradient measured
      before and after therapy was assessed by paired samples t-test, and survival
      analysis was made by the Kaplan-Meier method. RESULTS: IPS was successfully
      created in all patients. The mean duration of the thrombolytic therapy was 65.3
      +/- 29.5 h, and the mean concentration of urokinase used for the thrombolysis was
      2324000 +/- 945000 U. Comparison of the mean portosystemic gradients showed a
      significant improvement in response to the therapy (before: 33.8 +/- 4.9 mm Hg
      vs. after: 15.4 +/- 2.1 mm Hg; P less than 0.001). The overall rate of clinical
      improvement was 94.4%. One patient died on day 2 post-therapy and another two
      patients experienced mild hepatic encephalopathy or right hemothorax,
      respectively, on day 5 post-therapy, with conservative medical management
      achieving complete recovery for both. The mean follow-up time was 18.6 +/- 17.5
      months, during which only one patient died and five others experienced shunt
      dysfunction; all remaining patients showed maintenance of shunt patency without
      symptoms of recurrence. CONCLUSION: Mechanical thrombectomy combined with
      pharmacologic thrombolysis via the IPS assisted by percutaneous transhepatic
      approach is a safe and effective therapeutic option for patients with non-acute
      and symptomatic PVT.

PMID- 24331698
TI  - [Role of store-operated Ca2+ channels in primary hepatocytes under conditions of
      calcium overload and ethanol-induced injury].
AB  - OBJECTIVE: To investigate the role of store-operated calcium channels (SOCs) in
      primary hepatocytes under conditions of calcium overload and ethanol-induced
      injury. METHODS: The in vitro model of chronic ethanol-induced hepatocyte injury
      was established using primary hepatocytes isolated from Sprague-Dawley rats.
      Ethanol-induced changes (24, 48 and 72 h; 50, 100, 200, 400 and 800 mmol/L) in
      expression of the SOCs proteins stromal interaction molecule 1 (STIM1) and
      calcium release-activated calcium channel protein 1 (Oria1) were detected by
      qualitative PCR analysis (mRNA) and western blotting (protein). The possible role
      of these two SOCs proteins in the ethanol-induced extracellular calcium influx
      and related liver cell injury was determined by treating the cell system with
      various channel blockers (EGTA, La3+, and 2-APB). Cell viability was determined
      by MTT assay and cytosolic free calcium ion concentration was determined by flow
      cytometry. RESULTS: After 24 h of exposure to 0 (untreated) to 800 mM/L ethanol,
      the cell viability was reduced in a concentration-dependent manner. The 400
      mmol/L concentration of ethanol decreased cell viability by 57.34% +/- 2.34%. and
      was chosen for use in subsequent experiments. Compared with the untreated control
      cells, the ethanol-treated cells showed significantly up-regulated mRNA and
      protein expression of both STIM1 and Orai1 at all times examined, suggesting that
      the ethanol-stimulated expression of STIM1 and Orai1 could persist for at least
      72 h. The ethanol treatment induced increase in cytoplasmic calcium levels was
      significantly (and similarly) reduced by co-treatment with any of the three
      channel blockers. CONCLUSION: Chronic ethanol exposure can increase the
      expression of STIM1 and Orai1 in primary liver cells, suggesting that ethanol may
      increase extracellular calcium influx by up-regulating expression of these SOCs
      protein molecules, ultimately aggravating liver cell damage.

PMID- 24331699
TI  - [Potential molecular mechanisms of quercetin-induced heme oxygenase-1 in rat
      primary hepatocytes].
AB  - OBJECTIVE: To investigate the possible molecular mechanisms of heme oxygenase-1
      (HO-1) induction by quercetin using rat primary hepatocytes. METHODS: Sprague
      Dawley rat primary hepatocytes were isolated using a two-step collagenase
      perfusion technique and treated with quercetin at various doses (25 - 200
      mumol/L) and times (2 - 12 h). To investigate the roles of various signaling
      pathways, the hepatocytes were pre-treated with 50 mumol/L quercetin plus an
      extracellular signal-regulated kinase (ERK) inhibitor (PD98059 at 10 mumol/L), a
      p38 inhibitor (SB203580 at 10 mumol/L), a c-Jun N-terminal kinase inhibitor
      (SP600125 at 10 mumol/L) or a phosphatidylinositol 3-kinase inhibitor (Wortmannin
      at 1 mumol/L) for 12 h. Changes in the mRNA and protein levels of HO-1 and
      nuclear factor, E-2 related factor 2 (Nrf2) were detected by RT-PCR and western
      blotting. RESULTS: After 4 - 12 h of treatment with quercetin at all
      concentrations, the HO-1 mRNA level in hepatocytes had increased significantly
      (vs. untreated control cells; all P less than 0.01). The quercetin-induced HO-1
      expression and Nrf2 translocation into the nucleolus was inhibited by PD98059.
      CONCLUSION: Quercetin may induce HO-1 expression via the ERK/Nrf2 signaling
      transduction pathway.

PMID- 24331700
TI  - [Changes in mast cells and hepatic expression of c-kit and stem cell factor in
      the rat model of chronic hepatitis].
AB  - OBJECTIVE: To study the potential role of mast cells and the related molecular
      mechanism in chronic hepatitis (CH) using a rat model system. METHODS: Thirty
      Wistar rats (15 males, 15 females; weight range: 230-290 g) were randomly divided
      into the normal contrast (NC) group and experimental CH group. The CH group
      received subcutaneous injection of CCl4 and a diet high in cholesterol and
      alcohol content and low in protein and choline content. Throughout the 4-week
      modeling period, aseptic blood samples were taken to test plasma tryptase (TS)
      and hyaluronic acid (HA) levels. The rats were euthanized to assess the changes
      in liver mast cells by histology and morphology analyses and the changes in liver
      expression of c-kit and stem cell factor (SCF) proteins by immunohistochemistry
      and mRNAs by RT-PCR. RESULTS: Compared to the NC group, the CH group had higher
      plasma and liver concentration of HA (78.09 +/- 38.55 vs. 145.14 +/- 52.54 ng/ml,
      51.58 +/- 20.45 vs. 106.59 +/- 43.15 ng/100 mg; t = 2.457 and 2.825 respectively,
      both P less than 0.05) and TS (0.416 +/- 0.143 vs 0.753 +/- 0.210 mg/ml; t =
      4.165, P less than 0.05). The CH group also showed fatty degeneration and
      fibrosis with many degranulating and degranulated mast cells filled with purple
      granula located around the liver blood vessels and in fiber-intervals. The CH
      livers also showed a significantly higher number of mast cells (2.167 +/- 0.924
      vs. NC: 10.92 +/- 1.575; t = 7.633, P less than 0.05) and stronger intensity of c
      kit staining (2.783 +/- 0.577 vs. 12.86 +/- 3.126; t = 9.511, P less than 0.05)
      and SCF staining (3.383 +/- 1.583 vs. 15.58 +/- 6.431; t = 9.625, P less than
      0.05). The expressions of c-kit and SCF were positively correlated with HA level
      (r = 0.478 and 0.556 respectively, both P less than 0.05). The c-kit and SCF mRNA
      expression levels were also significantly higher in the CH liver tissues.
      CONCLUSION: Mast cell degranulation and histamine release is significantly
      increased under conditions of chronic hepatitis, and the related mechanism may
      involve up-regulation of the membrane receptor c-kit and its ligand SCF.

PMID- 24331701
TI  - Acromio-clavicular joint cyst associated with a complete rotator cuff tear - a
      case report.
AB  - This case report describes a patient with an acromio-clavicular joint (ACJ) cyst,
      associated with a complete tear of the supraspinatus tendon, and the related
      arthropathy. Ultrasound was a suitable imaging modality to make the diagnosis,
      and rule out other pathologies. Full assessment of the rotator cuff must be
      carried out in the presence of ACJ cysts due to their common co-existence with
      large cuff tears. Cyst aspiration is not a suitable treatment, due to the high
      likelihood of recurrence. Optimal treatment requires management of the underlying
      rotator cuff tear. 

PMID- 24331702
TI  - Use of a fibrin-based system for enhancing angiogenesis and modulating
      inflammation in the treatment of hyperglycemic wounds.
AB  - The complex pathophysiology of chronic ulceration in diabetic patients is poorly
      understood; diabetes-related lower limb amputation is a major health issue, which
      has limited effective treatment regimes in the clinic. This study attempted to
      understand the complex pathology of hyperglycemic wound healing by showing
      profound changes in gene expression profiles in wounded human keratinocytes in
      hyperglycemic conditions compared to normal glucose conditions. In the hyper
      secretory wound microenvironment of hyperglycemia, Rab18, a secretory control
      molecule, was found to be significantly downregulated. Using a biomaterial
      platform for dual therapy targeting the two distinct pathways, this study aimed
      to resolve the major dysregulated pathways in hyperglycemic wound healing. To
      complement Rab18, and promote angiogenesis eNOS was also targeted, and this novel
      Rab18-eNOS therapy via a dynamically controlled 'fibrin-in-fibrin' delivery
      system, demonstrated enhanced wound closure, by increasing functional
      angiogenesis and reducing inflammation, in an alloxan-induced hyperglycemic
      preclinical ear ulcer model of compromised wound healing. 

PMID- 24331703
TI  - The role of energy dissipation of polymeric scaffolds in the mechanobiological
      modulation of chondrogenic expression.
AB  - Mechanical stimulation has been proposed to induce chondrogenesis in cell-seeded
      scaffolds. However, the effects of mechanical stimuli on engineered cartilage may
      vary substantially between different scaffolds. This advocates for the need to
      identify an overarching mechanobiological variable. We hypothesize that energy
      dissipation of scaffolds subjected to dynamic loading may be used as a
      mechanobiology variable. The energy dissipation would furnish a general criterion
      to adjust the mechanical stimulation favoring chondrogenesis in scaffold.
      Epiphyseal chondro-progenitor cells were then subject to unconfined compression 2
      h per day during four days in different scaffolds, which differ only by the level
      of dissipation they generated while keeping the same loading conditions.
      Scaffolds with higher dissipation levels upregulated the mRNA of chondrogenic
      markers. In contrast lower dissipation of scaffolds was associated with
      downregulation of chondrogenic markers. These results showed that energy
      dissipation could be considered as a mechanobiology variable in cartilage. This
      study also indicated that scaffolds with energy dissipation level close to the
      one of cartilage favors chondrogenic expression when dynamical loading is
      present.

PMID- 24331704
TI  - Stimuli-responsive biodegradable poly(methacrylic acid) based nanocapsules for
      ultrasound traced and triggered drug delivery system.
AB  - Ultrasound contrast agents (UCAs) have been investigated for echogenic
      intravenous drug delivery system. Due to the traditional UCAs with overlarge size
      (micro-scale), their reluctant accumulation in target organs and the instability
      have presented severe obstacles to the accurate response to the ultrasound and
      severely limited their further clinical application. Furthermore, elimination of
      drug carriers from the biologic system after their carrying out the diagnostic or
      therapeutic functions is one important aspect to be considered. The drug carriers
      with large sizes, avoiding renal filtration, will lead to increasing toxicity. In
      this present paper, we design and develop a new type of triple-stimuli responsive
      (ultrasound/pH/GSH) biodegradable nanocapsules, in which fill up with
      perfluorohexane, and the DOX-loaded PMAA with disulfide crosslinking forms the
      wall. These soft nanocapsules with uniform size of 300 nm can easily enter the
      tumor tissues via EPR effects. The PMAA shell has high DOX-loading content (36
      wt%) and great drug loading efficiency (93.5%), the PFH filled can effectively
      enhance US imaging signal through acoustic droplet vaporization (ADV), ensuring
      diagnostic and image-guided therapeutic applications. What is more, the disulfide
      crosslinked PMAA shell is biodegradable and thus safe for normal organisms. These
      merits enabled us optimize the balance of diagnostic, therapeutic and
      biodegradable functionalities in a multifunctional theranostic nanoplatform.

PMID- 24331705
TI  - Impact of macrophage deficiency and depletion on continuous glucose monitoring in
      vivo.
AB  - Although it is assumed that macrophages (MQ) have a major negative impact on
      continuous glucose monitoring (CGM), surprisingly there is no data in the
      literature to directly support or refute the role of MQ or related foreign body
      giant cells in the bio-fouling of glucose sensors in vivo. As such, we developed
      the hypothesis that MQ are key in controlling glucose sensor performance and CGM
      in vivo and MQ deficiencies or depletion would enhance CGM. To test this
      hypothesis we determined the presence/distribution of MQ at the sensor tissue
      interface over a 28-day time period using F4/80 antibody and immunohistochemical
      analysis. We also evaluated the impact of spontaneous MQ deficiency (op/op mice)
      and induced-transgenic MQ depletions (Diphtheria Toxin Receptor (DTR) mice) on
      sensor function and CGM utilizing our murine CGM system. The results of these
      studies demonstrated: 1) a time dependent increase in MQ accumulation (F4/80
      positive cells) at the sensor tissue interface; and 2) MQ deficient mice and MQ
      depleted C57BL/6 mice demonstrated improved sensor performance (MARD) when
      compared to normal mice (C57BL/6). These studies directly demonstrate the
      importance of MQ in sensor function and CGM in vivo.

PMID- 24331706
TI  - Multimodal nanoprobes to target cerebrovascular amyloid in Alzheimer's disease
      brain.
AB  - Cerebral amyloid angiopathy (CAA) results from the accumulation of Abeta proteins
      primarily within the media and adventitia of small arteries and capillaries of
      the cortex and leptomeninges. CAA affects a majority of Alzheimer's disease (AD)
      patients and is associated with a rapid decline in cognitive reserve.
      Unfortunately, there is no pre-mortem diagnosis available for CAA. Furthermore,
      treatment options are few and relatively ineffective. To combat this issue, we
      have designed nanovehicles (nanoparticles-IgG4.1) capable of targeting
      cerebrovascular amyloid (CVA) and serving as early diagnostic and therapeutic
      agents. These nanovehicles were loaded with Gadolinium (Gd) based
      (Magnevist((r))) magnetic resonance imaging contrast agents or single photon
      emission computed tomography (SPECT) agents, such as (125)I. In addition, the
      nanovehicles carry either anti-inflammatory and anti-amyloidogenic agents such as
      curcumin or immunosuppressants such as dexamethasone, which were previously shown
      to reduce cerebrovascular inflammation. Owing to the anti-amyloid antibody
      (IgG4.1) grafted on the surface, the nanovehicles are capable of specifically
      targeting CVA deposits. The nanovehicles effectively marginate from the blood
      flow to the vascular wall as determined by using quartz crystal microbalance with
      dissipation monitoring (QCM-D) technology. They demonstrate excellent
      distribution to the brain vasculature and target CVA, thus providing MRI and
      SPECT contrast specific to the CVA in the brain. In addition, they also display
      the potential to carry therapeutic agents to reduce cerebrovascular inflammation
      associated with CAA, which is believed to trigger hemorrhage in CAA patients. 

PMID- 24331707
TI  - Rose-bengal-conjugated gold nanorods for in vivo photodynamic and photothermal
      oral cancer therapies.
AB  - Gold nanorods (GNRs) conjugated with rose bengal (RB) molecules exhibit efficient
      singlet oxygen generation when illuminated by 532 nm green light and high
      photothermal efficiency under 810 nm near-infrared (NIR) irradiation. In vitro
      experiments show that reactive oxygen species generated by green light and
      hyperthermia produced by NIR light constitute two different mechanisms for cancer
      cell death. The RB-GNRs also exhibit improved photodynamic efficacy by enhancing
      the uptake of RB by cancer cells. In vivo experiments are conducted on hamster
      cheek pouches to resemble the human oral cancer conditions more accurately to
      assess the therapeutic effectiveness. Compared to the single photodynamic therapy
      (PDT) or photothermal therapy (PTT), the RB-GNRs with combined PDT-PTT
      capabilities provide better therapeutic effects against oral cancer and have
      large potential in cancer treatment.

PMID- 24331708
TI  - The effect of time-dependent deformation of viscoelastic hydrogels on myogenic
      induction and Rac1 activity in mesenchymal stem cells.
AB  - Cell behaviours within tissues are influenced by a broad array of physical and
      biochemical microenvironmental factors. Whilst 'stiffness' is a recognised
      physical property of substrates and tissue microenvironments that influences many
      cellular behaviours, tissues and their extracellular matrices are not purely
      rigid but 'viscoelastic' materials, composed of both rigid-like (elastic) and
      dissipative (viscous) elements. This viscoelasticity results in materials
      displaying increased deformation with time under the imposition of a defined
      force or stress, a phenomenon referred to as time-dependent deformation or
      'creep'. Previously, we compared the behaviour of human mesenchymal stem cells
      (hMSCs) on hydrogels tailored to have a constant stiffness, but to display
      varying levels of creep in response to an applied force. Using polyacrylamide as
      a model material, we showed that on high-creep hydrogels (HCHs), hMSCs displayed
      increased proliferation, spread area and differentiation towards multiple
      lineages, compared to their purely stiff analogue, with a particular propensity
      for differentiation towards a smooth muscle cell (SMC) lineage. In this present
      study, we investigate the mechanisms behind this phenomenon and show that hMSCs
      adhered to HCHs have increased expression of SMC induction factors, including
      soluble factors, ECM proteins and the cell-cell adhesion molecule, N-Cadherin.
      Further, we identify a key role for Rac1 signalling in mediating this increased N
      Cadherin expression. Using a real-time Rac1-FRET biosensor, we confirm increased
      Rac1 activation on HCHs, an observation that is further supported functionally by
      observed increases in motility and lamellipodial protrusion rates of hMSCs.
      Increased Rac1 activity in hMSCs on HCHs provides underlying mechanisms for
      enhanced commitment towards a SMC lineage and the compensatory increase in spread
      area (isotonic tension) after a creep-induced loss of cytoskeletal tension on
      viscoelastic substrates, in contrast to previous studies that have consistently
      demonstrated up-regulation of RhoA activity with increasing substrate stiffness.
      Tuning substrate viscoelasticity to introduce varying levels of creep thus equips
      the biomaterial scientist or engineer with a new tool with which to tune and
      direct stem cell outcomes. 

PMID- 24331710
TI  - Engineering interpenetrating network hydrogels as biomimetic cell niche with
      independently tunable biochemical and mechanical properties.
AB  - Hydrogels have been widely used as artificial cell niche to mimic extracellular
      matrix with tunable properties. However, changing biochemical cues in hydrogels
      developed-to-date would often induce simultaneous changes in mechanical
      properties, which do not support mechanistic studies on stem cell-niche
      interactions. Here we report the development of a PEG-based interpenetrating
      network (IPN), which is composed of two polymer networks that can independently
      and simultaneously crosslink to form hydrogels in a cell-friendly manner. The
      resulting IPN hydrogel allows independently tunable biochemical and mechanical
      properties, as well as stable and more homogeneous presentation of biochemical
      ligands in 3D than currently available methods. We demonstrate the potential of
      our IPN platform for elucidating stem cell-niche interactions by modulating
      osteogenic differentiation of human adipose-derived stem cells. The versatility
      of such IPN hydrogels is further demonstrated using three distinct and widely
      used polymers to form the mechanical network while keeping the biochemical
      network constant. 

PMID- 24331709
TI  - Discovery of antibiotics-derived polymers for gene delivery using combinatorial
      synthesis and cheminformatics modeling.
AB  - We describe the combinatorial synthesis and cheminformatics modeling of
      aminoglycoside antibiotics-derived polymers for transgene delivery and
      expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides
      with diglycidyl ether cross-linkers. Parallel screening resulted in
      identification of several lead polymers that resulted in high transgene
      expression levels in cells. The role of polymer physicochemical properties in
      determining efficacy of transgene expression was investigated using Quantitative
      Structure-Activity Relationship (QSAR) cheminformatics models based on Support
      Vector Regression (SVR) and 'building block' polymer structures. The QSAR model
      exhibited high predictive ability, and investigation of descriptors in the model,
      using molecular visualization and correlation plots, indicated that
      physicochemical attributes related to both, aminoglycosides and diglycidyl ethers
      facilitated transgene expression. This work synergistically combines
      combinatorial synthesis and parallel screening with cheminformatics-based QSAR
      models for discovery and physicochemical elucidation of effective antibiotics
      derived polymers for transgene delivery in medicine and biotechnology. 

PMID- 24331712
TI  - Composite hydrogel scaffolds incorporating decellularized adipose tissue for soft
      tissue engineering with adipose-derived stem cells.
AB  - An injectable tissue-engineered adipose substitute that could be used to deliver
      adipose-derived stem cells (ASCs), filling irregular defects and stimulating
      natural soft tissue regeneration, would have significant value in plastic and
      reconstructive surgery. With this focus, the primary aim of the current study was
      to characterize the response of human ASCs encapsulated within three-dimensional
      bioscaffolds incorporating decellularized adipose tissue (DAT) as a bioactive
      matrix within photo-cross-linkable methacrylated glycol chitosan (MGC) or
      methacrylated chondroitin sulphate (MCS) delivery vehicles. Stable MGC- and MCS
      based composite scaffolds were fabricated containing up to 5 wt% cryomilled DAT
      through initiation with long-wavelength ultraviolet light. The encapsulation
      strategy allows for tuning of the 3-D microenvironment and provides an effective
      method of cell delivery with high seeding efficiency and uniformity, which could
      be adapted as a minimally-invasive in situ approach. Through in vitro cell
      culture studies, human ASCs were assessed over 14 days in terms of viability,
      glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, adipogenic gene
      expression and intracellular lipid accumulation. In all of the composites, the
      DAT functioned as a cell-supportive matrix that enhanced ASC viability, retention
      and adipogenesis within the gels. The choice of hydrogel also influenced the cell
      response, with significantly higher viability and adipogenic differentiation
      observed in the MCS composites containing 5 wt% DAT. In vivo analysis in a
      subcutaneous Wistar rat model at 1, 4 and 12 weeks showed superior implant
      integration and adipogenesis in the MCS-based composites, with allogenic ASCs
      promoting cell infiltration, angiogenesis and ultimately, fat formation.

PMID- 24331711
TI  - The effect of a polyurethane-based reverse thermal gel on bone marrow stromal
      cell transplant survival and spinal cord repair.
AB  - Cell therapy for nervous tissue repair is limited by low transplant survival. We
      investigated the effects of a polyurethane-based reverse thermal gel,
      poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU) on bone marrow
      stromal cell (BMSC) transplant survival and repair using a rat model of spinal
      cord contusion. Transplantation of BMSCs in ESHU at three days post-contusion
      resulted in a 3.5-fold increase in BMSC survival at one week post-injury and a
      66% increase in spared nervous tissue volume at four weeks post-injury. These
      improvements were accompanied by enhanced hindlimb motor and sensorimotor
      recovery. In vitro, we found that ESHU protected BMSCs from hydrogen peroxide
      mediated death, resulting in a four-fold increase in BMSC survival with two-fold
      fewer BMSCs expressing the apoptosis marker, caspase 3 and the DNA oxidation
      marker, 8-oxo-deoxyguanosine. We argue that ESHU protected BMSCs transplanted is
      a spinal cord contusion from death thereby augmenting their effects on
      neuroprotection leading to improved behavioral restoration. The data show that
      the repair effects of intraneural BMSC transplants depend on the degree of their
      survival and may have a widespread impact on cell-based regenerative medicine.

PMID- 24331713
TI  - Amino-functionalized nanoparticles as inhibitors of mTOR and inducers of cell
      cycle arrest in leukemia cells.
AB  - Activation of the mammalian target of rapamycin (mTOR) has been implicated in
      anticancer drug resistance, type 2 diabetes, and aging. Here, we show that
      surface functionalization of polystyrene nanoparticles with amino groups (PS
      NH2), but not with carboxyl groups (PS-COOH), induces G2 cell-cycle arrest and
      inhibition of proliferation in three leukemia cell lines. Besides, PS-NH2 inhibit
      angiogenesis and proliferation of leukemia cells xenografted onto the chick
      chorioallantoic membrane. At the molecular level, PS-NH2 inhibit, whereas PS-COOH
      activate mTOR signaling in leukemia cells. Consistently, PS-NH2 block activation
      of the mTOR downstream targets, Akt and p70 ribosomal S6 kinase 1, and induce
      overexpression of the cell-cycle regulator p21(Cip1/Waf1) and degradation of
      cyclin B1. After addition, both types of particles rapidly induce autophagy in
      leukemia cells. Yet, only in PS-NH2-treated cells, acidic vesicular organelles
      show elevated pH and impaired processing of procathepsin B. Moreover, solely in
      PS-NH2-treated cells, autophagy is followed by permeabilization of acidic
      vesicular organelles and induction of apoptosis. By contrast, primary
      macrophages, which do not exhibit activated mTOR signaling, proved relatively
      resistant to PS-NH2-induced toxicity. These data indicate that functionalized
      nanoparticles can be used to control activation of mTOR signaling pathways, and
      to influence proliferation and viability of malignant cells. 

PMID- 24331715
TI  - Building sustainable organizational capacity to deliver HIV programs in resource
      constrained settings: stakeholder perspectives.
AB  - BACKGROUND: In 2008, the US government mandated that HIV/AIDS care and treatment
      programs funded by the US President's Emergency Plan for AIDS Relief (PEPFAR)
      should shift from US-based international partners (IPs) to registered locally
      owned organizations (local partners, or LPs). The US Health Resources and
      Services Administration (HRSA) developed the Clinical Assessment for Systems
      Strengthening (ClASS) framework for technical assistance in resource-constrained
      settings. The ClASS framework involves all stakeholders in the identification of
      LPs' strengths and needs for technical assistance. OBJECTIVE: This article
      examines the role of ClASS in building capacity of LPs that can endure and adapt
      to changing financial and policy environments. DESIGN: All stakeholders (n=68) in
      Kenya, Zambia, and Nigeria who had participated in the ClASS from LPs and IPs,
      the US Centers for Disease Control and Prevention (CDC), and, in Nigeria,
      HIV/AIDS treatment facilities (TFs) were interviewed individually or in groups
      (n=42) using an open-ended interview guide. Thematic analysis revealed
      stakeholder perspectives on ClASS-initiated changes and their sustainability.
      RESULTS: Local organizations were motivated to make changes in internal
      operations with the ClASS approach, PEPFAR's competitive funding climate,
      organizational goals, and desired patient health outcomes. Local organizations
      drew on internal resources and, if needed, technical assistance from IPs.
      Reportedly, ClASS-initiated changes and remedial action plans made LPs more
      competitive for PEPFAR funding. LPs also attributed their successful funding
      applications to their preexisting systems and reputation. Bureaucracy, complex
      and competing tasks, and staff attrition impeded progress toward the desired
      changes. Although CDC continues to provide technical assistance through IPs,
      declining PEPFAR funds threaten the consolidation of gains, smooth program
      transition, and continuity of treatment services. CONCLUSIONS: The well-timed
      adaptation and implementation of ClASS successfully engaged stakeholders who
      committed their own resources toward strengthening organizational capacity. The
      sustainability of built capacity depends on continued investment in leadership,
      staff retention, and quality improvement.

PMID- 24331714
TI  - Effects of pre- and postnatal nutrition interventions on child growth and body
      composition: the MINIMat trial in rural Bangladesh.
AB  - BACKGROUND: Nutritional insults and conditions during fetal life and infancy
      influence subsequent growth and body composition of children. OBJECTIVES: Effects
      of maternal food and micronutrient supplementation and exclusive breastfeeding
      counseling on growth of offspring aged 0-54 months and their body composition at
      54 months of age were studied. METHODS: In the MINIMat trial (ISRCTN16581394) in
      Matlab, Bangladesh, pregnant women were randomized to early (around 9 weeks) or
      usual invitation (around 20 weeks) to food supplementation and to one of the
      three daily micronutrient supplements: 30-mg Fe and 400-ug folic acid (Fe30F), 60
      mg Fe and 400-ug folic acid (Fe60F), and multiple micronutrient supplements
      (MMS). The supplements were also randomized to exclusive breastfeeding (EBF)
      counseling or to usual health messages. RESULTS: No differences in background
      characteristics were observed among the intervention groups. There was also no
      differential effect of prenatal interventions on birthweight or birthlength.
      Early food supplementation reduced the level of stunting from early infancy up to
      54 months of age among boys (average difference - 6.5% units, 95% confidence
      interval [CI] 1.7-11.3, p=0.01) but not among girls (average difference - 2.4%
      units, 95% CI -2.2-7.0, p=0.31). MMS resulted in more stunting compared to
      standard Fe60F (average difference - 4.8% units, 95% CI 0.8-8.9, p=0.02).
      Breastfeeding counseling prolonged the duration of EBF (difference - 35 days, 95%
      CI 30.6-39.5, p<0.001). Neither pregnancy interventions nor breastfeeding
      counseling influenced the body composition of children at 54 months of age.
      CONCLUSION: Early food supplementation during pregnancy reduced the occurrence of
      stunting among boys aged 0-54 months, while prenatal MMS increased the proportion
      of stunting. Food and micronutrient supplementation or EBF intervention did not
      affect body composition of offspring at 54 months of age. The effects of prenatal
      interventions on postnatal growth suggest programming effects in early fetal
      life.

PMID- 24331716
TI  - Pharmacokinetics of gamithromycin after intravenous and subcutaneous
      administration in pigs.
AB  - The aim of this study was to investigate the pharmacokinetic properties of
      gamithromycin in pigs after an intravenous (i.v.) or subcutaneous (s.c.) bolus
      injection of 6 mg/kg body weight. The plasma concentrations of gamithromycin were
      determined using a validated high-performance liquid chromatography-tandem mass
      spectrometry method, and the pharmacokinetics were noncompartmentally analysed.
      Following i.v. administration, the mean area under the plasma concentration-time
      curve extrapolated to infinity (AUCinf) and the mean elimination half-life
      (t1/2lambdaz) were 3.67 +/- 0.75 MUg.h/mL and 16.03 h, respectively. The volume
      of distribution at steady state (Vss) and the plasma clearance were 31.03 +/-
      6.68 L/kg and 1.69 +/- 0.33 L/h.kg, respectively. The mean residence time
      (MRTinf) was 18.84 +/- 4.94 h. Gamithromycin administered subcutaneously to pigs
      demonstrated a rapid and complete absorption, with a mean maximal plasma
      concentration (Cmax) of 0.41 +/- 0.090 MUg/ml at 0.63 +/- 0.21 h and a high
      absolute bioavailability of 118%. None of the reported pharmacokinetic variables
      significantly differed between both administration routes.

PMID- 24331717
TI  - Emergency department identification and critical care management of a Utah prison
      botulism outbreak.
AB  - STUDY OBJECTIVE: We report botulism poisoning at a state prison after ingestion
      of homemade wine (pruno). METHODS: This is an observational case series with data
      collected retrospectively by chart review. All suspected exposures were referred
      to a single hospital in October 2011. RESULTS: Twelve prisoners consumed pruno, a
      homemade alcoholic beverage made from a mixture of ingredients in prison
      environments. Four drank pruno made without potato and did not develop botulism.
      Eight drank pruno made with potato, became symptomatic, and were hospitalized.
      Presenting symptoms included dysphagia, diplopia, dysarthria, and weakness. The
      median time to symptom onset was 54.5 hours (interquartile range [IQR] 49-88
      hours) postingestion. All 8 patients received botulinum antitoxin a median of 12
      hours post-emergency department admission (IQR 8.9-18.8 hours). Seven of 8
      patients had positive stool samples for type A botulinum toxin. The 3 most
      severely affected patients had respiratory failure and were intubated 43, 64, and
      68 hours postingestion. Their maximal inspiratory force values were -5, -15, and 
      30 cm H2O. Their forced vital capacity values were 0.91, 2.1, and 2.2 L, whereas
      the 5 nonintubated patients had median maximal inspiratory force of -60 cm H2O
      (IQR -60 to -55) and forced vital capacity of 4.5 L (IQR 3.7-4.9).
      Electromyography abnormalities were observed in 1 of the nonintubated and 2 of
      the intubated patients. CONCLUSION: A pruno-associated botulism outbreak resulted
      in respiratory failure and abnormal pulmonary parameters in the most affected
      patients. Electromyography abnormalities were observed in the majority of
      intubated patients. Potato in the pruno recipe was associated with botulism.

PMID- 24331718
TI  - [BRAF: the pathologist's favorite oncogene].

PMID- 24331719
TI  - [Cellular and molecular mechanisms of carcinogenic side effects and resistance to
      BRAF inhibitors in metastatic melanoma with BRAFV600 mutation: state of the
      knowledge].
AB  - Cutaneous melanoma is a malignant tumor with a high metastatic potential. If an
      early treatment is associated with a favorable outcome, the prognosis of
      metastatic melanoma remains poor. Advances in molecular characterization of
      cancers, notably the discovery of BRAF gene mutations in metastatic melanoma,
      allowed to the recent development of targeted therapies against mutated BRAF
      protein. Despite high tumor response rates observed in clinical trials, these new
      drugs are associated with frequent secondary tumor resistance occurrence and
      paradoxical carcinogenic side effects. The cellular and molecular mechanisms of
      these carcinogenic side effects and secondary resistance are not yet fully
      elucidated and are actually intensely studied. This review of the literature
      focus on the mechanisms of these carcinogenic side effects and on the tumor
      resistance associated with anti-BRAF targeted therapies. 

PMID- 24331720
TI  - [The accreditation of a surgical pathology and somatic genetic laboratory (LPCE,
      CHU of Nice) according to the ISO 15189 norm: Sharing of experience].
AB  - Accreditation is going to be vital and unavoidable in the medium term for medical
      biology laboratories in France. This accreditation will certainly condition the
      authorization to conduct biological testing in the health care system. All the
      biological specialities are now affected by this procedure, including the somatic
      genetics. The anatomo-pathology, which is a medical speciality in France, may be
      also concerned by the accreditation. However, the nature and the practices of
      this specialty increase the complexity of this approach to be implemented
      according to the standard requested by the authorities, i.e. the ISO 15189
      normative standard (standard on "specific requirements for quality and competence
      for medical biology analysis laboratories"). The present article recounts the
      experience of a hospital laboratory (LPCE, Nice University Hospital) composed of
      a surgical pathology and a somatic genetics unit: (1) in the accreditation
      process according to the ISO 15189 standard, (2) at the time of the audit made by
      the team of "COFRAC" evaluators, and, (3) in evaluating the strategy implemented
      following the audit. 

PMID- 24331721
TI  - [Adenocarcinoma of minor salivary gland origin: a recently described lesion. A
      case report].
AB  - Cribriform adenocarcinoma of salivary gland origin is a rare and recently
      described lesion. In spite of the high incidence of metastatic spread, the
      prognosis remains very good. We report a case of a 64-year-old man with
      cribriform adenocarcinoma of salivary gland origin of the ventral tongue without
      locoregional or distant metastasis. The patient is currently 43-month post
      treatment without any local or regional recurrence of the disease. This entity
      should be kept in mind regarding its good prognosis and its resemblances with
      papillary carcinoma of the thyroid and adenoid cystic carcinoma with which it
      should not be confused. 

PMID- 24331722
TI  - ["Growing teratoma syndrome": an unrecognized complication of treated germ cell
      tumors of the testis].
AB  - "Growing teratoma syndrome" is a rare and often unrecognized complication of
      nonseminomatous germ cell tumors of the testis. It is defined by enlarging
      residual masses, frequently retroperitonal, composed exclusively by teratoma,
      during the course of chemotherapy. Complications of this syndrome are due to
      masses compression. Malignant transformation is also possible. "Growing teratoma
      syndrome" has a good prognosis when cured by complete surgical excision of the
      tumoral masses. We report the case of a "growing teratoma syndrome" presenting as
      a retroperitoneal mass occurring in a patient previously treated by orchiectomy
      and chemotherapy for a nonseminomatous mixed germ cell tumors of the testis
      without teratomatous component. 

PMID- 24331723
TI  - [Two cases reports of pancreatic endocrine microadenoma incidentally found].
AB  - A 59-year-old male, was admitted to our hospital for a tumor of the pancreatic
      tail. Serum CEA and CA 19-9 levels were normal. Splenopancreasectomy found a
      desmoid tumour. A 69-year-old male was referred to our institution for chronic
      anemia and inflammatory syndrome with splenomegaly. Splenectomy showed an
      important splenic congestion and siderosis. Both patients had a type 2 diabetes
      mellitus. Furthermore, histological examination revealed pancreatic endocrine
      microadenomas. The two patients' postoperative course was unremarkable. Eleven
      and 24 months respectively after the diagnosis, the patients are alive and well,
      with no tumor recurrence. 

PMID- 24331724
TI  - [Invasive fungal rhinosinusitis in an apparently immunocompetant patient].
AB  - The incidence of invasive fungal rhinosinusitis is constantly increasing, due to
      the growing number of immunocompromised patients. We report the case of a 73-year
      old patient with a severe aortic stenosis whose preoperative evaluation revealed
      a recurrence of a left maxillary sinusitis operated many years ago. The patient
      underwent meatotomy and drainage. Pathologic examination of the sinus mucosa
      revealed the presence of septate and branched fungal hyphae invading the blood
      vessels. The diagnosis of invasive aspergillosis was thus established and the
      patient was treated by oral voriconazole. Our report describes the case of an
      invasive chronic form of a fungal rhinosinusitis occurring in an
      immunocompromised patient, and exposes the different forms of invasive fungal
      rhinosinusitis. The diagnosis of an invasive form of fungal rhinusinusitis should
      be suspected in immunocompromised patients in particular, but also in
      immunocompetent patients. The appropriate treatment should be promptly set up,
      given the bad prognosis of acute and fulminant cases. 

PMID- 24331725
TI  - [An open heart lesion].

PMID- 24331726
TI  - [A colourful villous atrophy].

PMID- 24331727
TI  - [An uncommon spleen tumor].

PMID- 24331728
TI  - [A sudden cardiac arrest during the anesthesia induction].

PMID- 24331729
TI  - [About a rare maxillary tumour].

PMID- 24331730
TI  - Trematode infections in pregnant ewes can predispose to mastitis during the
      subsequent lactation period.
AB  - Objective was to investigate if trematode infections predispose ewes to mastitis
      and/or metritis. We used 80 trematode-infected ewes: primigravidae in group P-A
      and multigravidae in M-A remained untreated, primigravidae in P-B and
      multigravidae in M-B were drenched with netobimin and multigravidae in M-C were
      given rafoxanide. We collected faecal samples for parasitological examination,
      blood samples for beta-hydroxybutyrate concentration measurement and uterine
      content, teat duct material and milk samples for bacteriological examination. We
      found significant differences in blood beta-hydroxybutyrate concentrations
      between M-A, M-B and M-C during pregnancy (P ? 0.002). We did not observe
      significant differences between groups regarding development of metritis
      (P>0.83). We found that for M-A, M-B and M-C ewes, respectively, median time to
      first case of mastitis was 5.75, 21 and 6.75 days after lambing (P = 0.003) and
      incidence risk of mastitis was 0.308, 0.069 and 0.222 (P = 0.047). We postulate
      that trematode infections predispose ewes to mastitis; perhaps, increased beta
      hydroxybutyrate blood concentrations adversely affect mammary cellular defences.
      This is the first report associating parasitic infections with mastitis in sheep.

PMID- 24331731
TI  - Letter to the editor: minimally invasive surgery for malignant adrenal tumors.

PMID- 24331732
TI  - Quantifying the excess cost and resource utilisation for patients with
      complications associated with elective knee arthroscopy: a retrospective cohort
      study.
AB  - BACKGROUND: Recent studies have demonstrated morbidity associated with elective
      knee arthroscopy. The objective of the current study was to quantify resource
      utilisation and costs associated with postoperative complications following an
      elective knee arthroscopy. METHODS: We undertook a retrospective, longitudinal
      cohort study using routinely collected hospital data from Victorian public
      hospitals during the period from 1 July 2000 to 30 June 2009. A generalised
      linear model was used to examine relative cost and length of stay for venous
      thromboembolism, joint complications and infections. Log-transformed multiple
      linear regression and retransformation were used to determine the excess cost
      after adjustment. RESULTS: We identified 166,770 episodes involving an elective
      knee arthroscopy. There were a total of 976(0.6%) complications, including 573
      patients who had a venous thromboembolism (VTE) (0.3%), 227 patients with a joint
      complication (0.1%) and 141 patients with infections (0.1%). After adjustment,
      the excess 30-day cost per patient for venous thromboembolism was $USD +3227 (95%
      CI: $3211-3244), for joint complications it was $USD +2247 (95% CI: $2216-2280)
      and for infections it was $USD +4364 (95% CI: $4331-4397). CONCLUSION: This is
      the first study to quantify resource utilisation for complications associated
      with elective knee arthroscopy. With growing attention focused on improving
      patient outcomes and containing costs, understanding the nature and impact of
      complications on resource utilisation is important.

PMID- 24331733
TI  - Risk factors of lameness in sows in England.
AB  - Lameness in pigs is a major welfare concern and one of the most commonly reported
      reasons for premature culling of breeding sows. In this study, the prevalence of
      lameness in sows was estimated using data from 76 pig breeding units in England
      and risk factors associated with the occurrence of lameness were examined. The
      prevalence of lameness in sows was 4.5% (farm median 5.0%, range 0-40%), with at
      least one lame sow being observed at 54% of the 76 farms. Relative risk (RR) of
      lameness was determined by multivariable Poisson regression analysis. Farms with
      high producing sows had a lower rate of lame sows than farms with a medium level
      of production (P=0.01). However, medium levels of production on a farm were
      associated with higher levels of lameness than farms having the lowest level of
      production (P=0.02). Farms where the stockman had responsibility for more sows
      resulted in an increased risk of lameness (P=0.0062). When indoor units were
      considered, the area of the pen and younger sows (two parities or less) had
      higher risk of lameness (P=0.001 and P=0.026 respectively). An increased
      awareness of the risk factors behind lameness is essential in farm management and
      can be useful when designing housing areas as well as developing future
      prevention plans for lameness. 

PMID- 24331734
TI  - Orthognathic surgery with or without induced hypotension.
AB  - This study involved a retrospective evaluation of patients subjected to surgery
      for dentofacial deformities treated without induced controlled hypotension (group
      I, n=50) and a prospective evaluation of patients who were subjected to surgery
      under hypotensive general anaesthesia (group II, n=50). No statistical
      differences were found between the study groups with regard to the duration of
      surgery. However, there were statistically significant differences in the need
      for blood transfusion and the occurrence of bradycardia during the maxillary down
      fracture. Hypotensive anaesthesia decreased the need for a blood transfusion and
      the occurrence of bradycardia, and is therefore considered highly beneficial for
      patients undergoing orthognathic surgery.

PMID- 24331735
TI  - Functional dynamics of cell surface membrane proteins.
AB  - Cell surface receptors are integral membrane proteins that receive external
      stimuli, and transmit signals across plasma membranes. In the conventional view
      of receptor activation, ligand binding to the extracellular side of the receptor
      induces conformational changes, which convert the structure of the receptor into
      an active conformation. However, recent NMR studies of cell surface membrane
      proteins have revealed that their structures are more dynamic than previously
      envisioned, and they fluctuate between multiple conformations in an equilibrium
      on various timescales. In addition, NMR analyses, along with biochemical and cell
      biological experiments indicated that such dynamical properties are critical for
      the proper functions of the receptors. In this review, we will describe several
      NMR studies that revealed direct linkage between the structural dynamics and the
      functions of the cell surface membrane proteins, such as G-protein coupled
      receptors (GPCRs), ion channels, membrane transporters, and cell adhesion
      molecules. 

PMID- 24331736
TI  - Bilateral sudden sensorineural hearing loss: review.
AB  - INTRODUCTION: Unilateral and bilateral sudden sensorineural hearing loss
      represent different disease entities. The unilateral condition is more common and
      predominantly idiopathic, and up to 65 per cent of patients spontaneously recover
      hearing. Conversely, the bilateral condition is rare, mostly associated with
      serious systemic conditions, and has a higher prevalence of morbidity and
      mortality. METHODS: A literature search using the PubMed database was conducted
      using the MeSH terms 'sudden', 'bilateral' and 'sensorineural hearing loss'.
      RESULTS: One hundred and three reported cases of bilateral sudden sensorineural
      hearing loss were identified. The condition is most often associated with toxic,
      autoimmune, neoplastic and vascular conditions. A younger age of onset, with a
      bimodal age distribution, was seen for bilateral sudden sensorineural hearing
      loss, compared with the unilateral condition. Patients with the bilateral
      condition had more profound hearing loss, with poorer recovery and a 35 per cent
      mortality rate. Vestibular symptoms were also less common than in the unilateral
      condition. CONCLUSION: The presentation of bilateral sudden onset sensorineural
      hearing loss is a medical emergency requiring thorough and urgent investigation
      to exclude life-threatening and reversible conditions.

PMID- 24331738
TI  - [Inverted takotsubo syndrome in the immediate post-operative period in a patient
      with morbid obesity].

PMID- 24331737
TI  - Increased decidual mRNA expression levels of candidate maternal pre-eclampsia
      susceptibility genes are associated with clinical severity.
AB  - INTRODUCTION: Pre-eclampsia (PE) has a familial association, with daughters of
      women who had PE during pregnancy having more than twice the risk of developing
      PE themselves. Through genome-wide linkage and genetic association studies in PE
      affected families and large population samples, we previously identified the
      following as positional candidate maternal susceptibility genes for PE; ACVR1,
      INHA, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2. The aims of this study were
      to determine mRNA expression levels of previously identified candidate maternal
      pre-eclampsia susceptibility genes from normotensive and severe PE (SPE)
      pregnancies and correlate mRNA expression levels with the clinical severity of
      SPE. METHODS: Third trimester decidual tissues were collected from both
      normotensive (n = 21) and SPE pregnancies (n = 24) and mRNA expression levels
      were determined by real-time PCR. Gene expression was then correlated with
      several parameters of clinical severity in SPE. Statistical significance was
      determined by Mann-Whitney U test and Spearman's Correlation. RESULTS: The data
      demonstrate significantly increased decidual mRNA expression levels of ACVR1,
      INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2 in SPE (p < 0.05). Increased mRNA
      expression levels of several genes - INHA, INHBB, COL4A1 and COL4A2 were
      correlated with earlier onset of PE and earlier delivery of the fetus (p < 0.05).
      CONCLUSION: These results suggest altered expression of maternal susceptibility
      genes may play roles in PE development and the course of disease severity.

PMID- 24331739
TI  - Neurotrophic factors in women with crack cocaine dependence during early
      abstinence: the role of early life stress.
AB  - BACKGROUND: Neurotrophic factors have been investigated in the pathophysiology of
      alcohol and drug dependence and have been related to early life stress driving
      developmental programming of neuroendocrine systems. METHODS: We conducted a
      follow-up study that aimed to assess the plasma levels of glial cell line-derived
      neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve
      growth factor (NGF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5) in crack
      users during 3 weeks of early abstinence in comparison with healthy controls. We
      performed a comprehensive clinical assessment in female inpatients with crack
      cocaine dependence (separated into 2 groups: participants with (CSA+) and without
      (CSA-) a history of childhood sexual abuse) and a group of nonuser control
      participants. RESULTS: Our sample included 104 women with crack cocaine
      dependence and 22 controls; of the women who used crack cocaine, 22 had a history
      of childhood sexual abuse and 82 did not. The GDNF plasma levels in the CSA+
      group increased dramatically during 3 weeks of detoxification. In contrast, those
      in the CSA- group showed lower and stable levels of GDNF under the same
      conditions. Compared with the control group, BDNF plasma levels remained elevated
      and NGF levels were reduced during early abstinence. We found no differences in
      NT3 and NT4/5 between the patients and controls. However, within-group analyses
      showed that the CSA+ group exhibited higher levels of NT4/5 than the CSA- group
      at the end of detoxification. LIMITATIONS: Some of the participants were using
      neuroleptics, mood stabilizers or antidepressants; our sample included only
      women; memory bias could not be controlled; and we did not investigate the
      possible confounding effects of other forms of stress during childhood.
      CONCLUSION: This study supports the association between early life stress and
      peripheral neurotrophic factor levels in crack cocaine users. During early
      abstinence, plasmastic GDNF and NT4/5 were the only factors to show changes
      associated with a history of childhood sexual abuse.

PMID- 24331741
TI  - [Results of treatment of scaphoid nonunion with microvascularized bone grafts of
      the 1, 2 intercompartmental supraretinacular artery and osteosynthesis].
AB  - OBJECTIVE: To analyze the results of treatment of scaphoid nonunion with
      questionable viability of the proximal fragment, but without significant
      deformity or collapse, using a vascularized bone graft of 1,2 intercompartmental
      supraretinacular artery (1.2 ICSRA) and subsequent osteosynthesis. MATERIAL AND
      METHOD: A retrospective study was performed on 10 male patients with a
      radiographic diagnosis of nonunion. Functionality, pain using Visual Analog Score
      (VAS), grip strength, patient satisfaction and reintroduction to working life,
      using QuickDASH and May specific wrist scales were assessed after the treatment.
      The integration of the graft was checked by radiography. RESULTS: The mean follow
      up was 31.4 months, and 90% of the questionnaires were satisfactory. The VAS
      decreased by 4.6 points and the flexor-extensor mobility gain was 5 degrees . The
      total graft consolidation rate reached 40% in 5.5 months on average. DISCUSSION:
      Several studies have demonstrated better results using vascularized bone graft
      versus non-vascularized. From the description by Zaidemberg in 1991, the
      vascularized graft with 1.2 ICSRA artery, distal radius, has been the most widely
      used for the treatment of scaphoid nonunion. CONCLUSIONS: Our results are
      comparable with the literature reviewed, thus using vascular graft of the 1.2
      ICSRA and osteosynthesis with Herbert-type screw, may be an alternative treatment
      for proximal scaphoid nonunion, without collapse or significant deformity.

PMID- 24331740
TI  - Angiogenesis inhibition and depression in older men.
AB  - BACKGROUND: Cardiovascular diseases have been associated with depression in later
      life, and a potential mechanism is inhibition of angiogenesis. We designed this
      study to determine if depression is associated with higher serum concentration of
      endostatin, an endogenous angiogenesis inhibitor. METHODS: We performed a cross
      sectional examination of a random sample of men aged 69-86 years. Those who
      scored 7 or higher on the 15-item Geriatric Depression Scale were deemed
      depressed. We determined the concentration of serum endostatin using a
      reproducible assay. Other measures included age, education, body mass index,
      smoking, history of depression, use of antidepressants, hypertension, diabetes,
      coronary heart disease and stroke, high sensitivity C-reactive protein, plasma
      homocysteine, triglycerides and cholesterol. We used logistic regression to
      investigate the association between endostatin and depression, and adjusted the
      analyses for confounding factors. RESULTS: Our sample included 1109 men. Sixty
      three (5.7%) men were depressed. Their serum endostatin was higher than that of
      nondepressed participants (p = 0.021). Men in the highest decile of endostatin
      had greater adjusted odds of depression (odds ratio [OR] 1.78, 95% confidence
      interval [CI] 1.03-3.06). A doubling of endostatin doubled the odds of depression
      (OR 1.93, 95% CI 1.31-2.84). The probability of depression increased with the
      concentration of endostatin in a log-linear fashion up to a maximum of about 20%
      25%. LIMITATIONS: The cross-sectional design limits the study's ability to
      ascribe causality to the association between high endostatin and depression.
      CONCLUSION: Serum endostatin is associated with depression in older men. It
      remains to be established whether correction of this imbalance is feasible and
      could decrease the prevalence of depression in later life.

PMID- 24331742
TI  - [Usefulness of magnetic resonance imaging in the evaluation of patellar
      malalignment].
AB  - OBJECTIVES: The aim of this study is to evaluate the usefulness of Magnetic
      Resonance Imaging (MRI) at 20 degrees  of knee flexion in patients with
      patellofemoral pain syndrome (PFPS) caused by suspected patellofemoral
      malalignment (PFM). MATERIAL AND METHOD: Fifty MRIs were performed on 25 patients
      with PFPS secondary to suspected PFM based on clinical examination, and on 25
      patients without PFPS (control group). Measurements were made of tibial
      tuberosity-trochlear groove distance (TTTG) and modified Laurin, Merchant and
      trochlear angles. The results were analyzed with ANOVA and Fischer tests. Pearson
      correlation coefficients were used to analyze differences between PFPS and
      control cases. Specificity, sensitivity, positive predictive value and negative
      predictive value for knee pain were documented. RESULTS: Significant differences
      were observed between PFPS and control groups in TTTG (11.79 mm vs. 9.35 mm;
      P=.002), Laurin angle (12.17 degrees  vs. 15.56 degrees ; P=.05), and trochlear
      angle (139 degrees  vs. 130.02 degrees ; P=.049). No differences were found
      between groups as regards the Merchant angle (P=.5). TTTG was 70% predictive of
      PFPS; however, it was only 53.33% specific, with a sensitivity of 51.61% for
      PFPS. Laurin angle was 77.78% predictive of PFPS, with a specificity of 92% and a
      sensitivity of 28%. Trochlear angle was 85.71% predictive of PFPS, with a
      specificity of 96% and a sensitivity of 24%. CONCLUSIONS: MRI can confirm
      clinically suspected PFPS secondary to malalignment. MRI determination of TTTG,
      patellar tilt, and trochlear angle correlates positively with clinical diagnosis
      of PFPS, suggesting that PFPS is caused by subtle malalignment.

PMID- 24331743
TI  - Performance of skin tests with allergens from B. melitensis B115 and rough B.
      abortus mutants for diagnosing swine brucellosis.
AB  - Swine brucellosis by Brucella suis biovar 2 is an emerging disease whose control
      is based on serological testing and culling. However, current serological tests
      detect antibodies to the O-polysaccharide (O/PS) moiety of Brucella smooth
      lipopolysaccharide (S-LPS), and thus lack specificity when infections by Yersinia
      enterocolitica O:9 and other gram-negative bacteria carrying cross-reacting O/PS
      occur. The skin test with the protein-rich brucellin extract obtained from rough
      B. melitensis B115 is assumed to be specific for discriminating these false
      positive serological reactions (FPSR). However, B115 strain, although unable to
      synthesize S-LPS, accumulates O/PS internally, which could cause diagnostic
      problems. Since the brucellin skin test has been seldom used in pigs and FPSR are
      common in these animals, we assessed its performance using cytosoluble protein
      extracts obtained from B. abortus rough mutants in manBcore or per genes
      (critical for O/PS biosynthesis) and B. melitensis B115. The diagnostic
      sensitivity and specificity were determined in B. suis biovar 2 culture positive
      and brucellosis free sows, and apparent prevalence in sows of unknown individual
      bacteriological and serological status belonging to B. suis biovar 2 naturally
      infected herds. Moreover, the specificity in discriminating brucellosis from FPSR
      was assessed in brucellosis free boars showing FPSR. The skin test with B.
      abortus DeltamanBcore and B. melitensis B115 allergens performed similarly, and
      the former one resulted in 100% specificity when testing animals showing FPSR in
      indirect ELISA, Rose Bengal and complement fixation serological tests. We
      conclude that O/PS-free genetically defined mutants represent an appropriate
      alternative to obtain Brucella protein extracts for diagnosing swine brucellosis.

PMID- 24331744
TI  - Pheno- and genotypic analysis of antimicrobial resistance properties of Yersinia
      ruckeri from fish.
AB  - Enteric red-mouth disease, caused by Yersinia ruckeri, is an important disease in
      rainbow trout aquaculture. Antimicrobial agents are frequently used in
      aquaculture, thereby causing a selective pressure on bacteria from aquatic
      organisms under which they may develop resistance to antimicrobial agents. In
      this study, the distribution of minimal inhibitory concentrations (MICs) of
      antimicrobial agents for 83 clinical and non-clinical epidemiologically unrelated
      Y. ruckeri isolates from north west Germany was determined. Antimicrobial
      susceptibility was conducted by broth microdilution at 22 +/- 2 degrees C for 24,
      28 and 48 h. Incubation for 24h at 22 +/- 2 degrees C appeared to be suitable for
      susceptibility testing of Y. ruckeri. In contrast to other antimicrobial agents
      tested, enrofloxacin and nalidixic acid showed a bimodal distribution of MICs,
      with one subpopulation showing lower MICs for enrofloxacin (0.008-0.015 MUg/mL)
      and nalidixic acid (0.25-0.5 MUg/mL) and another subpopulation exhibiting
      elevated MICs of 0.06-0.25 and 8-64 MUg/mL, respectively. Isolates showing
      elevated MICs revealed single amino acid substitutions in the quinolone
      resistance-determining region (QRDR) of the GyrA protein at positions 83 (Ser83
      Arg or -Ile) or 87 (Asn87-Tyr), which raised the MIC values 8- to 32-fold for
      enrofloxacin or 32- to 128-fold for nalidixic acid. An isolate showing elevated
      MICs for sulfonamides and trimethoprim harbored a ~ 8.9 kb plasmid, which carried
      the genes sul2, strB and a dfrA14 gene cassette integrated into the strA gene.
      These observations showed that Y. ruckeri isolates were able to develop mutations
      that reduce their susceptibility to (fluoro)quinolones and to acquire plasmid
      borne resistance genes.

PMID- 24331745
TI  - Comprehensive control of human papillomavirus infections and related diseases.
AB  - Infection with human papillomavirus (HPV) is recognized as one of the major
      causes of infection-related cancer worldwide, as well as the causal factor in
      other diseases. Strong evidence for a causal etiology with HPV has been stated by
      the International Agency for Research on Cancer for cancers of the cervix uteri,
      penis, vulva, vagina, anus and oropharynx (including base of the tongue and
      tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide,
      4.8% were attributable to HPV infection, with substantially higher incidence and
      mortality rates seen in developing versus developed countries. In recent years,
      we have gained tremendous knowledge about HPVs and their interactions with host
      cells, tissues and the immune system; have validated and implemented strategies
      for safe and efficacious prophylactic vaccination against HPV infections; have
      developed increasingly sensitive and specific molecular diagnostic tools for HPV
      detection for use in cervical cancer screening; and have substantially increased
      global awareness of HPV and its many associated diseases in women, men, and
      children. While these achievements exemplify the success of biomedical research
      in generating important public health interventions, they also generate new and
      daunting challenges: costs of HPV prevention and medical care, the implementation
      of what is technically possible, socio-political resistance to prevention
      opportunities, and the very wide ranges of national economic capabilities and
      health care systems. Gains and challenges faced in the quest for comprehensive
      control of HPV infection and HPV-related cancers and other disease are summarized
      in this review. The information presented may be viewed in terms of a reframed
      paradigm of prevention of cervical cancer and other HPV-related diseases that
      will include strategic combinations of at least four major components: 1) routine
      introduction of HPV vaccines to women in all countries, 2) extension and
      simplification of existing screening programs using HPV-based technology, 3)
      extension of adapted screening programs to developing populations, and 4)
      consideration of the broader spectrum of cancers and other diseases preventable
      by HPV vaccination in women, as well as in men. Despite the huge advances already
      achieved, there must be ongoing efforts including international advocacy to
      achieve widespread-optimally universal-implementation of HPV prevention
      strategies in both developed and developing countries. This article summarizes
      information from the chapters presented in a special ICO Monograph 'Comprehensive
      Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5,
      2012. Additional details on each subtopic and full information regarding the
      supporting literature references may be found in the original chapters. 

PMID- 24331747
TI  - Infrastructure requirements for human papillomavirus vaccination and cervical
      cancer screening in sub-Saharan Africa.
AB  - The availability of both human papillomavirus (HPV) vaccination and alternative
      screening tests has greatly improved the prospects of cervical cancer prevention
      in sub-Saharan African (SSA) countries. The inclusion of HPV vaccine in the
      portfolio of new vaccines offered by the Gobal Alliance for Vaccines and
      Immunization (GAVI) to GAVI-eligible countries has vastly improved the chances of
      introducing HPV vaccination. Further investments to improve vaccine storage,
      distribution and delivery infrastructure and human resources of the Extended
      Programme of Immunization will substantially contribute to the faster
      introduction of HPV vaccination in SSA countries through both school- and
      campaign-based approaches. Alternative methods to cytology for the prevention of
      cervical cancer through the early detection and treatment of cervical cancer
      precursors have been extensively evaluated in the past 15 years, in Africa as
      well as in other low-resource settings. Visual inspection with 3-5% dilute acetic
      acid (VIA) and HPV testing are the two alternative screening methods that have
      been most studied, in both cross-sectional and randomised clinical trials. VIA is
      particularly suitable to low-resource settings; however, its efficacy in reducing
      cervical cancer is likely to be significantly lower than HPV testing. The
      introduction of VIA screening programmes will help develop the infrastructure
      that will, in turn, facilitate the introduction of affordable HPV testing in
      future. Links with the existing HIV/AIDS control programmes is another strategy
      to improve the infrastructure and screening services in SSA. Infrastructural
      requirements for an integrated approach aiming to vaccinate single-year cohorts
      of girls in the 9-13 years age-range and to screen women over 30 years of age
      using VIA or affordable rapid HPV tests are outlined in this manuscript. This
      article forms part of a regional report entitled "Comprehensive Control of HPV
      Infections and Related Diseases in the Sub-Saharan Africa Region" Vaccine Volume
      31, Supplement 5, 2013. Updates of the progress in the field are presented in a
      separate monograph entitled "Comprehensive Control of HPV Infections and Related
      Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24331746
TI  - The burden of human papillomavirus infections and related diseases in sub-saharan
      Africa.
AB  - Despite the scarcity of high quality cancer registries and lack of reliable
      mortality data, it is clear that human papillomavirus (HPV)-associated diseases,
      particularly cervical cancer, are major causes of morbidity and mortality in sub
      Saharan Africa (SSA). Cervical cancer incidence rates in SSA are the highest in
      the world and the disease is the most common cause of cancer death among women in
      the region. The high incidence of cervical cancer is a consequence of the
      inability of most countries to either initiate or sustain cervical cancer
      prevention services. In addition, it appears that the prevalence of HPV in women
      with normal cytology is higher than in more developed areas of the world, at an
      average of 24%. There is, however, significant regional variation in SSA, with
      the highest incidence of HPV infection and cervical cancer found in Eastern and
      Western Africa. It is expected that, due to aging and growth of the population,
      but also to lack of access to appropriate prevention services and the concomitant
      human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      epidemic, cervical cancer incidence and mortality rates in SSA will rise over the
      next 20 years. HPV16 and 18 are the most common genotypes in cervical cancer in
      SSA, although other carcinogenic HPV types, such as HPV45 and 35, are also
      relatively more frequent compared with other world regions. Data on other HPV
      related anogenital cancers including those of the vulva, vagina, anus, and penis,
      are limited. Genital warts are common and associated with HPV types 6 and 11. HIV
      infection increases incidence and prevalence of all HPV-associated diseases.
      Sociocultural determinants of HPV-related disease, as well as the impact of
      forces that result in social destabilization, demand further study. Strategies to
      reduce the excessive burden of HPV-related diseases in SSA include age
      appropriate prophylactic HPV vaccination, cervical cancer prevention services for
      women of the reproductive ages, and control of HIV/AIDS. This article forms part
      of a regional report entitled "Comprehensive Control of HPV Infections and
      Related Diseases in the Sub-Saharan Africa Region" Vaccine Volume 31, Supplement
      5, 2013. Updates of the progress in the field are presented in a separate
      monograph entitled "Comprehensive Control of HPV Infections and Related Diseases"
      Vaccine Volume 30, Supplement 5, 2012.

PMID- 24331748
TI  - Trials and projects on cervical cancer and human papillomavirus prevention in sub
      Saharan Africa.
AB  - Cervical cancer is the leading cause of cancer morbidity and mortality in women
      in sub-Saharan Africa (SSA), accounting for about 50,000 deaths annually. Until
      recently, cytology was the gold standard for screening and prevention of cervical
      cancer. This method of screening has not been successful in SSA due to a lack of
      human, financial and material resources and poor health care infrastructure. It
      is estimated that less than 5% of at risk women have ever being screened. In the
      past two decades alternative approaches to cytology for cervical cancer screening
      have been evaluated in low- and medium-income countries. Visual inspection with
      acetic acid (VIA) and/or Lugol's iodine (VILI) have been shown to have adequate
      sensitivity, although low specificity, in a number of cross-sectional research
      and demonstration projects. Visual inspection methods require minimal resources,
      are technologically accessible, and are feasible for screening for precancerous
      lesions. Linking screening with VIA/VILI to treatment with cryotherapy may enable
      screening and treatment to take place in one visit, but this is likely to result
      in large numbers of women being subjected to unnecessary treatment. A number of
      studies have shown that cryotherapy is not associated with significant side
      effects or complications and is well tolerated. Creating the infrastructure for
      screening of older women is considered desirable, despite the limitations of
      visual inspection methods as screening tests. Understanding the role of human
      papillomavirus (HPV) infection in the etiology of cervical cancer and the
      discovery of HPV rapid test kits, as well as the development of vaccines against
      the HPV oncogenic types, have created new opportunities for prevention of
      cervical cancer. Trials and projects have established (and are still ongoing) the
      feasibility of using these molecular tests for screening. The ultimate in
      prevention method is primary prevention, offered by the advent of prophylactic
      vaccines against the most important oncogenic types, namely HPV16 and 18. This
      article forms part of a regional report entitled "Comprehensive Control of HPV
      Infections and Related Diseases in the Sub-Saharan Africa Region" Vaccine Volume
      31, Supplement 5, 2013. Updates of the progress in the field are presented in a
      separate monograph entitled "Comprehensive Control of HPV Infections and Related
      Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24331749
TI  - Model-based impact and cost-effectiveness of cervical cancer prevention in sub
      Saharan Africa.
AB  - Using population and epidemiologic data for 48 countries in sub-Saharan Africa,
      we used a model-based approach to estimate cervical cancer cases and deaths
      averted, disability-adjusted life years (DALYs) averted and incremental cost
      effectiveness ratios (I$ (international dollar) per DALY averted) for human
      papillomavirus (HPV) vaccination of pre-adolescent girls. Additional
      epidemiologic data from Uganda and South Africa informed estimates of cancer risk
      reduction and cost-effectiveness ratios associated with pre-adolescent female
      vaccination followed by screening of women over age 30. Assuming 70% vaccination
      coverage, over 670,000 cervical cancer cases would be prevented among women in
      five consecutive birth cohorts vaccinated as young adolescents; over 90% of cases
      averted were projected to occur in countries eligible for GAVI Alliance support.
      There were large variations in health benefits across countries attributable to
      differential cancer rates, population size, and population age structure. More
      than half of DALYs averted in sub-Saharan Africa were in Nigeria, Tanzania,
      Uganda, the Democratic Republic of the Congo, Ethiopia, and Mozambique. When the
      cost per vaccinated girl was I$5 ($0.55 per dose), HPV vaccination was cost
      saving in 38 sub-Saharan African countries, and cost I$300 per DALY averted or
      less in the remaining countries. At this vaccine price, pre-adolescent HPV
      vaccination followed by screening three times per lifetime in adulthood cost
      I$300 per year of life saved (YLS) in Uganda (per capita GDP I$1,140) and I$1,000
      per YLS in South Africa (per capita GDP I$9,480). In nearly all countries
      assessed, HPV vaccination of pre-adolescent girls could be very cost-effective if
      the cost per vaccinated girl is less than I$25-I$50, reflecting a vaccine price
      being offered to the GAVI Alliance. In-country decision makers will need to
      consider many other factors, such as affordability, acceptability, feasibility,
      and competing health priorities, when making decisions about cervical cancer
      prevention. This article forms part of a regional report entitled "Comprehensive
      Control of HPV Infections and Related Diseases in the Sub-Saharan Africa Region"
      Vaccine Volume 31, Supplement 5, 2013. Updates of the progress in the field are
      presented in a separate monograph entitled "Comprehensive Control of HPV
      Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24331750
TI  - Recommendations for cervical cancer prevention in sub-saharan Africa.

PMID- 24331751
TI  - Human papillomavirus infection and related cancers in sub-Saharan Africa: burden
      and tools for prevention.

PMID- 24331752
TI  - The path to eliminate cervical cancer in the world and the challenges of
      professional education.

PMID- 24331753
TI  - Diminishing glutathione availability and age-associated decline in neuronal
      excitability.
AB  - Oxidative stress is frequently implicated in diminished electrical excitability
      of aging neurons yet the foundations of this phenomenon are poorly understood.
      This study explored links between alterations in cellular thiol-redox state and
      age-associated decline in electrical excitability in identified neurons (right
      pedal dorsal 1 [RPeD1]) of the gastropod Lymnaea stagnalis. Intracellular thiol
      redox state was modulated with either dithiothreitol or membrane permeable ethyl
      ester of the antioxidant glutathione (et-GSH). Neuronal antioxidant demand was
      manipulated through induction of lipid peroxidation with 2,2'-azobis-2-methyl
      propanimidamide-dihydrochloride (AAPH). Glutathione synthesis was manipulated
      with buthionine sulfoximine (BSO). We show that; glutathione content of snail
      brains declines with age, whereas pyroglutamate content increases; treatment with
      AAPH and BSO alone aggravated the natural low excitability state of old RPeD1,
      but only the combination of AAPH + BSO affected electrical excitability of young
      RPeD1; et-GSH reversed this effect in young RPeD1; et-GSH and dithiothreitol
      treatment reversed age-associated low excitability of old RPeD1. Together, these
      data argue for a tight association between glutathione availability and the
      regulation of neuronal electrical excitability and indicate perturbation of
      cellular thiol-redox metabolism as a key factor in neuronal functional decline in
      this gastropod model of biological aging. 

PMID- 24331755
TI  - HIV now: why human rights matter more than ever.

PMID- 24331754
TI  - Socio-economic, behavioural, (neuro)psychological and clinical determinants of
      HRQoL in people living with HIV in Belgium: a pilot study.
AB  - INTRODUCTION: Due to highly active antiretroviral therapy (HAART), HIV-1
      infection has evolved from a lethal to a chronic disease. As such, health-related
      quality of life (HRQoL) has become an important outcome variable. The purpose of
      this study was to identify socio-economic, behavioural, (neuro)psychological and
      clinical determinants of HRQoL among people living with HIV (PLHIV). METHODS:
      This study was conducted between 1 January and 31 December 2012 at the AIDS
      Reference Centre of Ghent University Hospital, a tertiary care referral centre in
      Belgium. Validated self-report questionnaires were administered to collect socio
      demographic data, to assess HRQoL (Medical Outcomes Study-HIV), depressive
      symptoms (Beck Depression Inventory-II) and adherence to HAART (Short Medication
      Adherence Questionnaire) and to screen for neurocognitive dysfunction. RESULTS: A
      total of 237 people participated, among whom 187 (78.9%) were male. Mean age was
      45.8+/-10.7 years and 144 (63.7%, 144/226) participants were homosexual. Median
      physical and mental health score (PHS, MHS) were 55.6 (IQR 48.2-60.6) and 52.0
      (IQR 44.2-57.9), respectively. Multivariable regression analysis revealed that
      incapacity to work, depressive symptoms, neurocognitive complaints (NCCs),
      dissatisfaction with the patient-physician relationship and non-adherence were
      all negatively associated with HRQoL. CONCLUSIONS: Socio-economic (work status),
      behavioural (adherence) and (neuro)psychological (depressive symptoms, NCCs)
      determinants independently impact HRQoL among this cohort of PLHIV. Clinical
      parameters (viral load, CD4 cell count) were not independently associated with
      HRQoL.

PMID- 24331756
TI  - Pyrrolizines: Promising scaffolds for anticancer drugs.
AB  - Pyrrolizine derivatives constitute a class of heterocyclic compounds which can
      serve as promising scaffolds for anticancer drugs. The unique antitumor
      properties of mitomycin C inspired chemists to develop different pyrrolizine
      systems and assess their potential antitumor activities against a wide variety of
      cancer types. Here we review the different classes of pyrrolizines that possess
      anticancer potency, with an emphasis on their structure activity relationships,
      in an effort to pave the way for further development in this promising area of
      research. 

PMID- 24331757
TI  - Discovery of the rapanone and suberonone mixture as a motif for leishmanicidal
      and antifungal applications.
AB  - Leishmaniasis and fungal infections are significant diseases impacting worldwide
      public health. Treatments have developed greatly over time, however, there is a
      necessity to discover less toxic drugs, which have greater efficacy and are more
      economically accessible. This work conducted a screening of Cerrado species
      extracts: Connarus suberosus Planch. (Connaraceae), Neea theifera Oerst.
      (Nyctaginaceae) and Myrcia linearifolia Cambess. (Myrtaceae) against Leishmania
      (Leishmania) amazonensis, dermatophytes and yeasts. Leishmanicidal and antifungal
      tests were conducted using MTT colorimetric assay and CLSI methodology,
      respectively. Connarus suberosus extracts presented the most promising results
      against the aforementioned microorganisms, which has not been described in the
      literature. The root bark EtOAc extract was selected for chemical fractionation
      resulting in a mixture of rapanone (1) and a previously unreported compound named
      as suberonone (2); a mixture of beta-sitosterol (3) and stigmasterol (4); oleic
      acid (5); geranilgeraniol (6); and two derivatives obtained from 1 and 2 mixture.
      The rapanone and suberonone mixture demonstrated a MIC of 15.62 MUg/mL against
      Candida albicans ATCC 10231.

PMID- 24331758
TI  - Involvement of apoptosis and autophagy in the death of RPMI 8226 multiple myeloma
      cells by two enantiomeric sigma receptor ligands.
AB  - Over-expression of sigma receptors by many tumor cell lines makes ligands for
      these receptors attractive as potential chemotherapeutic drugs. Enantiomeric
      piperazines (S)-4 and (R)-4 were prepared as potential sigma-receptor ligands in
      a chiral pool synthesis starting from (S)- and (R)-aspartate. Both compounds
      showed high affinities for the sigma1 and sigma2 receptors. In the human multiple
      myeloma cell line RPMI 8226, a line expressing high levels of sigma receptors,
      both compounds inhibited cell proliferation with IC50 values in the low MUM
      range. No chiral differentiation between either the sigma receptor binding
      affinity or the cytotoxicity of the two enantiomers was observed. Both compounds
      induced apoptosis, which was evidenced by nuclear condensation, binding of
      annexin-V to phosphatidylserine in the outer leaf of the cell membrane, cleavage
      products of poly(ADP-ribose) polymerase-1 (PARP-1) and caspase-8 as well as the
      expression of bcl2 family members bax, bad and bid. However, apoptosis appeared
      to be caspase independent. Increased levels of the phosphorylated form of the
      microtubule associated protein light chain 3-II (LC3-II), an autophagosome
      marker, gave evidence that both compounds induced autophagy. However, further
      data (e.g., treatment with wortmannin) indicate that autophagy is incomplete and
      not cytoprotective. Lipid peroxidation (LPO) was observed in RPMI 8226 cells
      treated with the two compounds, and the lipid antioxidant alpha-tocopherol
      attenuated LPO. Interestingly, alpha-tocopherol reduced significantly both
      apoptosis and autophagy induced by the compounds. These results provide evidence
      that, by initiating LPO and changes in mitochondrial membrane potential, both
      compounds induce apoptosis and autophagy in RPMI 8226 cells.

PMID- 24331759
TI  - What does it really mean to "recover" from an operation?

PMID- 24331760
TI  - Delivery of intrahemocoelic peptides for insect pest management.
AB  - The extensive use of chemical insecticides for insect pest management has
      resulted in insecticide resistance now being recorded in >500 species of insects
      and mites. Although gut-active toxins such as those derived from Bacillus
      thuringiensis (Bt) have been successfully used for insect pest management, a
      diverse range of insect-specific insecticidal peptides remains an untapped
      resource for pest management efforts. These toxins act within the insect hemocoel
      (body cavity) and hence require a delivery system to access their target site.
      Here, we summarize recent developments for appropriate delivery of such
      intrahemocoelic insect toxins, via fusion to a second protein such as a plant
      lectin or a luteovirus coat protein for transcytosis across the gut epithelium,
      or via entomopathogenic fungi. 

PMID- 24331761
TI  - Addiction science advocacy: mobilizing political support to influence public
      policy.

PMID- 24331762
TI  - Cystic fibrosis: myths. mistakes, and dogma.
AB  - As a student I recall being told that half of what we would learn in medical
      school would be proven to be wrong. The challenges were to identify the incorrect
      half and, often more challenging, be willing to give up our entrenched ideas.
      Myths have been defined as traditional concepts or practice with no basis in
      fact. A misunderstanding is a mistaken approach or incomplete knowledge that can
      be resolved with better evidence, while firmly established misunderstandings can
      become dogma; a point of view put forth as authoritative without basis in fact.
      In this paper, I explore a number of myths, mistakes, and dogma related to cystic
      fibrosis disease and care. Many of these are myths that have long been vanquished
      and even forgotten, while others are controversial. In the future, many things
      taken as either fact or "clinical experience" today will be proven wrong. Let us
      examine these myths with an open mind and willingness to change our beliefs when
      justified. 

PMID- 24331763
TI  - Controversies in the diagnosis and treatment of sickle cell lung disease.

PMID- 24331764
TI  - Diagnostic utility of 123I-BMIPP imaging in patients with Takotsubo
      cardiomyopathy.
AB  - OBJECTIVE: Takotsubo cardiomyopathy is a cardiac syndrome with an acute onset
      defined by chest symptoms and ST segment elevation on electrocardiograms.
      Takotsubo cardiomyopathy is sometimes misdiagnosed as acute myocardial infarction
      (AMI). Therefore a non-invasive diagnostic method is needed to be established for
      setting up appropriate strategies. The purpose of this study was to detect
      myocardial metabolic abnormalities and to determine the diagnostic usefulness of
      (123)I-beta-methy-iodophenyl pentadecanoic acid ((123)I-BMIPP) imaging in
      patients with takotsubo cardiomyopathy. METHODS AND RESULTS: We examined 16
      patients with takotsubo cardiomyopathy and 12 with AMI in the left anterior
      descending artery. All patients were studied with resting (123)I-BMIPP imaging.
      Total defect score (TDS) of (123)I-BMIPP and perfusion were semi-quantitatively
      determined with single-photon emission computed tomography (SPECT) imaging using
      a 17-segment 5-point model. TDS of (123)I-BMIPP were 4.8 +/- 2.7 in patients with
      Takotsubo cardiomyopathy and 22.4 +/- 10.7 in AMI. The ratio of summed BMIPP
      defect score of non-apical to apical segments in Takotsubo cardiomyopathy was
      smaller than that of the patients with AMI (0.1 +/- 0.1 vs. 1.1 +/- 0.7, p <
      0.0001), indicating that (123)I-BMIPP abnormalities were exclusively observed the
      in apical area. The ratio of summed perfusion defect scores of non-apical to
      apical segments in takotsubo cardiomyopathy did not differ significantly from
      that of AMI (0.52 +/- 0.6 vs. 0.57 +/- 0.3, p = NS). Summed BMIPP defect score in
      the apical area of takotsubo cardiomyopathy was larger than that of perfusion
      defect score (3.9 +/- 2.7 vs. 1.8 +/- 1.8, p = 0.04). CONCLUSION: Impaired
      metabolic metabolism exclusively in the apical region was observed by (123)I
      BMIPP SPECT images in takotsubo cardiomyopathy. These typical metabolic SPECT
      features of the disease can be utilized on differential diagnosis of takotsubo
      cardiomyopathy.

PMID- 24331765
TI  - Risk factors for onset of depression after heart failure hospitalization.
AB  - BACKGROUND: Depression is common in chronic heart failure (CHF) and associated
      with adverse outcomes. Knowing the risk factors for the development of depression
      at the early post-hospitalization phase may be a key factor of successful disease
      management programs. The aim of this study was therefore to identify the risk
      factors related to the onset of depression after heart failure hospitalization in
      patients with CHF. METHODS: The study population included participants with an
      admission diagnosis of acute heart failure or exacerbation of CHF from a
      multicenter prospective cohort study. Patients completed clinical evaluation at
      discharge and functional and social status assessment at 1 month after discharge,
      and depressive symptoms using the Hospital Anxiety and Depression Scale (HADS-D)
      at discharge and 1-year later. RESULTS: Of the 131 patients without depression at
      discharge, 29 (22.1%) had developed significant depressive symptoms (HADS-D >= 8)
      at 1-year follow-up. Multiple logistic regression demonstrated that previous
      ischemic heart disease [odds ratio (OR) 3.09, 95% confidence interval (CI) 1.15
      8.33], participation restrictions (OR 0.43, 95% CI 0.26-0.70), and lack of
      satisfaction with social support (OR 0.48, 95% CI 0.29-0.79) were independent
      predictors of developing depression. CONCLUSIONS: The three clinically accessible
      variables and targets for interventions identified as predictors in this study
      may help to guide the optimal post-discharge disease management planning for
      these patients who are at high risk for depression.

PMID- 24331767
TI  - Medical device adverse incident reporting in interventional radiology.
AB  - AIM: To investigate the current situation concerning adverse incident reporting
      by members of the British Society of Interventional Radiology (BSIR). MATERIALS
      AND METHODS: A survey of the members of the BSIR was conducted between November
      2012 and January 2013. The survey contained questions on the reporting of adverse
      incidents and attitudes to the reading of "Instructions for Use" for new devices.
      RESULTS: The majority of the 119 members who completed the survey had experienced
      an adverse incident relating to the use of a device. Around 75% of respondents
      reported adverse incidents locally with only 42% reporting directly to the
      Medicines and Healthcare products Regulatory Agency (MHRA), which was explained
      by both a lack of time and a lack of awareness regarding mechanisms of reporting
      directly to the MHRA. CONCLUSION: Adverse incidents related to the unexpected
      failure of medical devices have been experienced by the majority of
      interventional radiologists. The majority of these are reported, but there is
      significant confusion as to where and how these should be reported. Improvements
      in the number and quality of adverse incidents reported requires better
      education, avoidance of duplication of work, and improved feedback after reports
      have been made to ensure the delivery of high-quality, safe patient care.

PMID- 24331768
TI  - Thoracic endometriosis syndrome: CT and MRI features.
AB  - Thoracic endometriosis is considered to be rare, but is the most frequent form of
      extra-abdominopelvic endometriosis. Thoracic endometriosis syndrome affects women
      of reproductive age. Diagnosis is mainly based on clinical findings, which can
      include catamenial pneumothorax and haemothorax, non-catamenial endometriosis
      related pneumothorax, catamenial haemoptysis, lung nodules, and isolated
      catamenial chest pain. Symptoms are typically cyclical and recurrent, with a
      right-sided predominance. Computed tomography (CT) is the first-line imaging
      method, but is poorly specific; therefore, its main role is to rule out other
      pulmonary diseases. However, in women with a typical clinical history, some key
      CT findings may help to confirm this often under-diagnosed syndrome. MRI can also
      assist with the diagnosis, by showing signal changes typical of haemorrhage
      within diaphragmatic or pleural lesions. 

PMID- 24331769
TI  - Australian otolaryngology research.

PMID- 24331770
TI  - Mini review on fructose metabolism.
AB  - Fructose is a monosaccharide and reducing sugar. It is present in sucrose and
      honey. Researchers around the world have come together in a just-published study
      that offers new ideas about how fructose consumption results in obesity and
      metabolic syndrome, which can lead to diabetes. In this review, we discuss that
      how fructose causes fatty liver, obesity and insulin resistance. We also discuss
      the effects of consumption of high fructose corn syrup, dietary fructose,
      fructose-induced changes in metabolism.:

PMID- 24331771
TI  - Beneficial effects of Chlorella on glucose and lipid metabolism in obese rodents
      on a high-fat diet.
AB  - BACKGROUND: Obesity-induced glucose and lipid metabolism disorders have become
      risk factors for lifestyle diseases. Powderized Parachlorella beijerinckii (BP)
      and its hot water extract (BCEx) are believed to be useful for preventing common
      diseases such as hypertension, arteriosclerosis, and hyperlipidemia. The present
      study investigated how chlorella components influence common diseases in obese
      mice and rats on a high-fat diet. METHODS: We fed C57BL/6J mice a high-fat diet
      containing 5% BP, and then weighed their organs, tested their glucose tolerance
      and insulin sensitivity, and analyzed their serum. Further, we fed Sprague-Dawley
      rats with a high-fat diet containing 1% BCEx, and then weighed their organs and
      analyzed their serum parameters. RESULTS: BP administration had no effect on high
      fat diet-induced obesity. However, compared with high-fat diet group, BP group
      had improved glucose tolerance and insulin sensitivity and inhibited the
      hypertrophic growth of visceral fat cells. In addition, BP group had improved
      serum adiponectin, leptin and monocyte chemoattractant protein-1 (MCP-1) levels.
      The MCP-1 expression level at epididymal fat was decreased at BP group. BCEx
      administration reduced amount of peritesticular fat and serum triglyceride (TG)
      levels. CONCLUSIONS: The results suggest that the antihyperinsulinemic effects of
      BP are due to the modulation of adipose tissue hypertrophy and adipocytokine
      secretion. BCEx inhibited the accumulation of visceral fat and serum TG. The
      study showed that BP and BCEx improve glucose and lipid metabolism disorders
      caused by a high-fat diet.

PMID- 24331772
TI  - Metabolic syndrome components are associated with DNA hypomethylation.
AB  - BACKGROUND: Disturbances of DNA methylation have been associated with multiple
      diseases, including cardiovascular disease, cancer and, as some have suggested,
      glucometabolic disturbances. Our aim was to assess the association of the
      metabolic syndrome and its individual components with DNA methylation in a
      population-based study. MATERIALS AND METHODS: In a human population (n = 738)
      stratified by age, sex and glucose metabolism, we explored associations of the
      metabolic syndrome according to National Cholesterol Education Program/Adult
      Treatment Panel-III criteria and its individual components (fasting glucose, high
      density lipoprotein cholesterol, triglycerides, blood pressure, waist
      circumference) with global leukocyte DNA methylation. DNA methylation was
      measured as the methylcytosine/cytosine ratio in peripheral leukocytes using
      liquid chromatography-tandem mass spectrometry. RESULTS: Individuals with the
      metabolic syndrome had relative DNA hypomethylation compared to participants
      without the syndrome (beta = -0.05; p = 0.01). This association was mainly
      attributable to linear associations of two metabolic syndrome components with DNA
      methylation: fasting plasma glucose (beta = -0.02; p = 0.004) and high-density
      lipoprotein cholesterol (beta = 0.07; p = 0.004). People with type 2 diabetes or
      impaired glucose metabolism had DNA hypomethylation compared to normoglycemic
      individuals (beta = -0.05; p = 0.004). CONCLUSIONS: DNA hypomethylation is
      independently associated with hyperglycemia and low high-density lipoprotein
      cholesterol, both essential components of the metabolic syndrome. The potential
      implications and direction of possible causality require further study.

PMID- 24331773
TI  - Effect of a family-based cognitive behavioural intervention on body mass index,
      self-esteem and symptoms of depression in children with obesity (aged 7-13): a
      randomised waiting list controlled trial.
AB  - OBJECTIVE: We examined the effect of a 12-week family-based cognitive behavioural
      weight management programme developed for use in primary care settings. METHODS:
      The sample consisted of 49 children with obesity (aged 7-13 years; mean +/- SD:
      10.68 +/- 1.24). Families were randomly assigned to immediate start-up of
      treatment or to a 12-week waiting list condition. Outcome measures were body mass
      index standard deviation score (BMI SDS), self-esteem, symptoms of depression and
      blood parameters indicative of cardio-metabolic risk. Assessments were conducted
      at baseline, post-treatment, post-waiting list and 12 months after treatment
      termination. RESULTS: The mean reduction for the treatment group was -0.16 BMI
      SDS units compared with an increase of 0.04 units for the waiting list group (p =
      .001). For the entire sample, there was a significant post-treatment improvement
      on BMI SDS (p = .001), all self-esteem measures (p = .001-.041) and symptoms of
      depression (p = .004). The mean BMI SDS reduction was -0.18 units post-treatment,
      and it was maintained at 12-month follow-up. Significant reductions were found in
      blood lipid levels of total cholesterol (p = .03), LDL-cholesterol (p = .005) and
      HDL-cholesterol (p = .01) at 12-month follow-up. The favourable effect on most of
      the psychological measures waned from post-treatment to follow-up, but not
      approaching baseline levels. Boys demonstrated significantly greater reductions
      in BMI SDS than girls (p = .001), while baseline psychiatric co-morbidity did not
      influence BMI SDS outcome. CONCLUSIONS: The treatment shows significant and
      favourable effects on BMI SDS, self-esteem and symptoms of depression compared
      with a waiting list condition.

PMID- 24331774
TI  - Periodontal treatment with topical antibiotics improves glycemic control in
      association with elevated serum adiponectin in patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVES: Chronic inflammation of periodontitis aggravates glycemic control in
      type 2 diabetic patients through aggravation of insulin resistance. Increased or
      decreased release of various inflammatory mediators, such as high sensitivity C
      reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6
      and adipokines, such as adiponectin, leptin, and resistin, are presumed to be
      responsible for developing and progressing insulin resistance. The purpose of
      this study was to examine the effects of periodontal treatment on glycemic
      control, serum inflammatory mediators and adipokines in type 2 diabetes patients
      with periodontitis. METHODS: Twenty-one type 2 diabetic patients with
      periodontitis received periodontal treatment with topical antibiotics
      (intervention group) and 8 patients did not receive periodontal treatment
      (control group). Periodontal examination, including probing pocket depth (PPD)
      and bleeding on probing (BOP), and blood sampling were performed at baseline, 2
      and 6 months after periodontal treatments. Glycated hemoglobin (HbA1c), hs-CRP,
      TNF-alpha, IL-6, adiponectin, leptin, and resistin were analyzed. RESULTS: In the
      intervention group, improvements of PPD and BOP, decrease in HbA1c and elevation
      of serum adiponectin were observed, while in the control group, all parameters
      were not changed. Generalized linear model revealed that changes of serum
      adiponectin and TNF-alpha and change of BOP correlated significantly with the
      reduction of HbA1c at 6 months after periodontal treatments. CONCLUSION: The
      results demonstrated that periodontal treatment improves periodontal status and
      glycemic control with elevation of serum adiponectin in type 2 diabetic patients.
      The results suggest that HbA1c is reduced by amelioration of insulin resistance
      due to elevated serum adiponectin after periodontal treatments.

PMID- 24331775
TI  - Effects of body weight reduction on cardio-ankle vascular index (CAVI).
AB  - OBJECTIVE: Obesity is associated with type 2 diabetes, dyslipidemia and
      hypertension, contributing to atherogenesis. Weight reduction is the fundamental
      therapy for obesity. Recently, a novel arterial stiffness parameter called cardio
      ankle vascular index (CAVI) has been developed. We hypothesized that CAVI may be
      a candidate marker of increased vascular stiffness in obese patients. The aim of
      this study is to investigate the effect of weight reduction on CAVI. SUBJECTS AND
      METHODS: Using CAVI as an indicator, we assessed the changes in arterial
      stiffness in 47 obese Japanese subjects (aged 46 +/- 13 years) who underwent a 12
      week weight reduction program consisting of a calorie restriction diet (20-25
      kcal/day) and exercise therapy. Visceral fat area (VFA) was evaluated by CT.
      RESULTS: At baseline, CAVI correlated positively with age (r = 0.70), blood
      pressure (r = 0.23), VFA (r = 0.26) and HbA1c (r = 0.39). After 12 weeks of
      weight reduction, mean BMI decreased from 33.3 +/- 7.5 to 30.7 +/- 6.4 kg/m(2) (p
      < 0.0001), and mean CAVI decreased from 8.3 to 7.9 (p < 0.01). The change in VFA
      correlated positively with change in CAVI in subjects with decrease in CAVI (r =
      0.47). Furthermore, change in VFA was a significant independent predictor for
      change in CAVI. No significant correlation was observed between change in CAVI
      and clinical variables such as BMI, HbA1c and lipids. CONCLUSION: This study
      demonstrated that CAVI decreased after weight reduction, and was associated with
      a decrease in VFA. CAVI reduction maybe a marker of improved vascular stiffness
      after weight reduction in subjects with visceral adiposity.

PMID- 24331776
TI  - Predicting success: factors associated with weight change in obese youth
      undertaking a weight management program.
AB  - OBJECTIVE: To explore which baseline physiological and psychosocial variables
      predict change in body mass index (BMI) z-score in obese youth after 12 weeks of
      a dietary weight management study. METHODS: Participants were obese young people
      participating in a dietary intervention trial in Brisbane Australia. The outcome
      variable was change in BMI z-score. Potential predictors considered included
      demographic, physiological and psychosocial parameters of the young person, and
      demographic characteristics of their parents. A multivariable regression model
      was constructed to examine the effect of potential predictive variables. RESULTS:
      Participants (n = 88) were predominantly female (69.3%), and had a mean(standard
      deviation) age of 13.1(1.9) years and BMI z-score of 2.2(0.4) on presentation.
      Lower BMI z-score (p < 0.001) and insulin resistance (p = 0.04) at baseline,
      referral from a paediatrician (p = 0.02) and being more socially advantaged (p =
      0.046) were significantly associated with weight loss. Macronutrient distribution
      of diet and physical activity level did not contribute. CONCLUSIONS: Early
      intervention in obesity treatment in young people improves likelihood of success.
      Other factors such as degree of insulin resistance, social advantage and referral
      source also appear to play a role. Assessing presenting characteristics and
      factors associated with treatment outcome may allow practicing clinicians to
      individualise a weight management program or determine the 'best-fit' treatment
      for an obese adolescent.

PMID- 24331777
TI  - Effects of regular exercise and nutritional guidance on body composition, blood
      pressure, muscle strength and health-related quality of life in community
      dwelling Japanese women.
AB  - OBJECTIVE: This study aimed to investigate the effects of 6-month regular
      exercise and nutritional guidance for body composition, blood pressure, muscle
      strength and health-related quality of life (HRQOL) in community-dwelling
      Japanese women aged 40-74 years. METHODS: Participants were divided into an
      intervention group (n = 48) comprising women registered for health guidance and a
      control group without intervention (n = 66). The intervention group received 6
      month exercise and nutritional guidance to modify lifestyle. Before and after the
      intervention period, body mass index (BMI), waist circumference, body fat
      percentage, blood pressure, muscle strength and HRQOL using the 36-item Short
      Form Health Survey version 2 (SF-36) questionnaire were measured. RESULTS: At
      baseline, no significant differences were found between intervention and control
      groups. Waist circumference decreased significantly in the intervention group
      (from 82.4 to 79.9 cm) compared to the control group (from 80.5 to 79.7 cm). BMI
      and body fat percentage also decreased significantly more in the intervention
      group than in the control group. General health perception, vitality and social
      functioning in the SF-36 showed significantly greater improvements in the
      intervention group than in the control group. CONCLUSIONS: Six-month regular
      exercise and nutritional guidance had beneficial effects on body composition and
      health-related quality of life especially for mental components of SF-36. Based
      on these findings, our intervention was expected to provide benefits to mental
      components of HRQOL and facilitate sustained participation and motivation in
      modify lifestyles. As a result, beneficial effects on body composition might also
      be sustained.

PMID- 24331778
TI  - Catestatin-like immunoreactivity in the rat eye.
AB  - The aim of the study was to investigate the presence and distribution of the
      chromogranin A-derived peptide catestatin in the rat eye and trigeminal ganglion
      by immunofluorescence using an antibody which recognizes not only free catestatin
      but also larger fragments containing the sequence of catestatin. Western blots
      were performed in an attempt to characterize the immunoreactivities detected by
      the catestatin antiserum. Sparse immunoreactive nerve fibers were visualized in
      the corneal stroma, in the chamber angle, in the sphincter muscle but also in
      association with the dilator muscle, in the stroma of the ciliary body and
      processes, but dense in the irideal stroma, around blood vessels at the limbus
      and in the choroid and in cells of the innermost retina representing amacrine
      cells as identified by colocalization with substance P. Furthermore, catestatin
      immunoreactivity was detected in the trigeminal ganglion in small to medium-sized
      cells and there were abundant catestatin-positive nerve fibers stained throughout
      the stroma of the ganglion. Double immunofluorescence of catestatin with
      substance P revealed colocalization both in cells of the trigeminal ganglion as
      well as in nerve fibers in the choroid. The immunoreactivities are present
      obviously as free catestatin and/or small-sized catestatin-containing fragments
      in the retina and ocular nerves but as large processed fragments as well, weak in
      the retina and more prominent in remaining ocular tissues, possibly in
      endothelial cells. This indicates that this peptide is a constituent of sensory
      neurons innervating the rat eye and the presence in amacrine cells in the retina
      is typical for neuropeptides. Catestatin is biologically highly active and might
      be of significance in the pathophysiology of the eye. 

PMID- 24331780
TI  - Stroke: new horizons in treatment.

PMID- 24331779
TI  - The effect of urocortin I on the hypothalamic ACTH secretagogues and its impact
      on the hypothalamic-pituitary-adrenal axis.
AB  - Urocortin I (UCN I) is a structural analogue of corticotropin-releasing factor
      (CRF), which, together with arginine-vasopressin (AVP), are the principle
      adrenocorticotropic hormone (ACTH) secretagogues in mammals. The aim of the
      present study was to investigate the effects of UCN I on the hypothalamic CRF and
      AVP concentration and its impact on the hypothalamic-pituitary-adrenal (HPA)
      axis. First, male Wistar rats were injected intracerebroventricularly (ICV) with
      0.5, 1, 2 and 5 MUg of UCN I. After 30 min hypothalamic CRF and AVP
      concentrations were determined by immunoassays. In parallel, the trunk blood was
      collected and plasma ACTH and corticosterone concentration was determined by
      ELISA and chemofluorescent assay, respectively. Second, rats were pretreated ICV
      with selective antagonists of receptors being implicated in the regulation of the
      HPA axis (0.1 MUg antalarmin for CRFR1, 1 MUg astressin 2B for CRFR2 or 0.1 MUg
      deamino-Pen1,Tyr2,Arg8-vasopressin for AVPR3) and treated ICV with the most
      effective dose of UCN I (5 MUg). After 30 min plasma corticosterone concentration
      was determined by chemofluorescent assay. UCN I induced dose-dependent
      augmentation of the hypothalamic CRF and AVP concentration, associated with dose
      dependent elevation of the plasma ACTH and corticosterone concentration. The most
      significant effect of UCN I on the plasma corticosterone concentration was
      inhibited by antalarmin, but was not influenced by astressin 2B or deamino
      Pen1,Tyr2,Arg8-vasopressin. The present study demonstrates that UCN I modulates
      the concentration of the hypothalamic ACTH secretagogues in parallel with the
      concentration of the plasma ACTH and corticosterone. Our results suggest that UCN
      I may activate the HPA axis by stimulation of the hypothalamic CRF production,
      and this process is mediated by CRFR1, and not by CRFR2. UCN I may stimulate the
      AVP production, as well, but, based on the results with AVPR3 antagonist, this
      effect is not involved in the regulation of the HPA axis.

PMID- 24331781
TI  - Alzheimer's disease and other dementias: advances in 2013.

PMID- 24331782
TI  - Highlights in headache research in 2013.

PMID- 24331783
TI  - Epilepsy: new genes, new technologies, new insights.

PMID- 24331784
TI  - Movement disorders: new insights into disease mechanisms and treatment.

PMID- 24331785
TI  - MS and related disorders: groundbreaking news.

PMID- 24331786
TI  - ALS and neuromuscular disease: in search of the Holy Grail.

PMID- 24331787
TI  - Traumatic brain injury: problems and opportunities.

PMID- 24331788
TI  - Paediatric neurology: a year of DNA technology.

PMID- 24331789
TI  - Sleep disorders matter in neurology.

PMID- 24331790
TI  - Brain infections in 2013: good drugs and bad bugs.

PMID- 24331791
TI  - Pain: what poisons are revealing about its mechanisms.

PMID- 24331792
TI  - Satoshi Kuwabara: work hard, rock hard.

PMID- 24331793
TI  - What's in an eponym?

PMID- 24331794
TI  - Vasculitic neuropathies.
AB  - The vasculitic neuropathies are a diverse group of disorders characterised by the
      acute-to-subacute onset of painful sensory and motor deficits that result from
      inflammatory destruction of nerve blood vessels and subsequent ischaemic injury.
      They are common in patients with primary systemic vasculitis and are seen in
      vasculitis secondary to disorders such as rheumatoid arthritis, viral infections,
      and diabetic inflammatory neuropathies. It is imperative that neurologists
      recognise these disorders to initiate treatment promptly and thereby prevent
      morbidity and mortality. To simplify the approach to patients with vasculitis of
      the peripheral nerves, a straightforward, dichotomous classification scheme can
      be used in which the vasculitic neuropathies are divided into two groups-nerve
      large arteriole vasculitis and nerve microvasculitis-on the basis of the size of
      the involved vessels. The size of the affected blood vessels correlates with the
      clinical course and prognosis in patients with vasculitic neuropathy. 

PMID- 24331795
TI  - Optic neuritis.
AB  - Acute optic neuritis is the most common optic neuropathy affecting young adults.
      Exciting developments have occurred over the past decade in understanding of
      optic neuritis pathophysiology, and these developments have been translated into
      treatment trials. In its typical form, optic neuritis presents as an inflammatory
      demyelinating disorder of the optic nerve, which can be associated with multiple
      sclerosis. Atypical forms of optic neuritis can occur, either in association with
      other inflammatory disorders or in isolation. Differential diagnosis includes
      various optic nerve and retinal disorders. Diagnostic investigations include MRI,
      visual evoked potentials, and CSF examination. Optical coherence tomography can
      show retinal axonal loss, which correlates with measures of persistent visual
      dysfunction. Treatment of typical forms with high-dose corticosteroids shortens
      the period of acute visual dysfunction but does not affect the final visual
      outcome. Atypical forms can necessitate prolonged immunosuppressive regimens.
      Optical coherence tomography and visual evoked potential measures are suitable
      for detection of neuroaxonal loss and myelin repair after optic neuritis.
      Clinical trials are underway to identify potential neuroprotective or
      remyelinating treatments for acutely symptomatic inflammatory demyelinating CNS
      lesions. 

PMID- 24331797
TI  - Body fluid biomarkers in multiple sclerosis.
AB  - Biomarkers can be thought of as multifaceted indicators of healthy status or of
      pathological disorders. The study of multiple sclerosis can benefit from the use
      of biomarkers because of the disease's inherent heterogeneity. Biomarkers in
      multiple sclerosis might assist with diagnosis, prediction of disease course, or
      identification of response outcome to treatments. Despite the need for biomarkers
      and extensive research to identify them, validation and clinical application of
      biomarkers is still an unmet need in multiple sclerosis, and large gaps remain
      between exploratory biomarkers proposed in many studies, validated biomarkers,
      and biomarkers that are integrated into routine clinical practice. 

PMID- 24331798
TI  - [Efficacy and safety of tirofiban use after successful percutaneous coronary
      intervention for patients with moderate to high risk non-ST segment elevation
      acute coronary syndromes].
AB  - OBJECTIVE: To evaluate the efficacy and safety of tirofiban use immediately after
      successful percutaneous coronary intervention (PCI) in patients with moderate to
      high risk non-ST segment elevation acute coronary syndromes (NSTE-ACS). METHODS:
      NSTE-ACS patients undergoing successful PCI (n = 246) were randomized by the
      envelope method to tirofiban group (n = 122, 10 ug/kg bolus within 3 min followed
      by 0.10-0.15 ug*kg(-1)*min(-1) for 36 h i.v.) or control group (n = 124, saline
      i.v. for 36 h). The primary efficacy composite end point was death, myocardial
      infarction, target vascular revascularization or ischemic stroke at 30 days. The
      second end point was the occurrence of composite end point at 7 days or 6 months.
      Key safety end points were bleeding and thrombocytopenia 3 days after PCI.
      RESULTS: Baseline characteristics were well-balanced between the two groups (P >
      0.05). The primary end point occurred in 0.9% (1/117) patients in the tirofiban
      group and 3.3% (4/123) patients of those in the control group (P = 0.40). There
      was no significant difference in the composite end point at 7 days [0.8% (1/122)
      vs. 3.2% (4/124), P = 0.38] between the groups, however, there was a trend
      towards lower composite efficacy end points at 6 months in tirofiban group
      compared to control group [0.9% (1/117) vs. 5.9% (7/118), P = 0.07]. The
      probability of survival free of composite end point was significantly higher in
      the tirofiban group than that in the control group (99.2% vs. 94.2%, log-rank
      test, P = 0.03). There was no GUSTO severe or moderate bleeding or severe
      thrombocytopenia within 3 days post-PCI. There was no significant difference in
      mild bleeding [13.1% (16/122) vs. 7.3% (9/124), P = 0.13] or mild
      thrombocytopenia [0.8% (1/122) vs. 0.8% (1/124), P = 1.00] between the groups.
      CONCLUSION: Tirofiban use after successful PCI can improve 6-month event-free
      survival without increasing the risk of bleeding for patients with moderate to
      high risk NSTE-ACS.

PMID- 24331799
TI  - [Comparison of short- and long-term outcome after percutaneous transluminal
      interventional therapy in octogenarians with coronary artery disease from radial
      or femoral approach].
AB  - OBJECTIVE: To compare the short-term and long-term outcome after percutaneous
      coronary intervention (PCI) between transradial intervention (TRI) and
      transfemoral intervention (TFI) in elderly patients. METHODS: From January 2005
      to December 2010, 488 consecutive elderly patients ( >= 80 years old) were
      enrolled in this retrospective study. Patients were divided into TRI group (n =
      235, PCIs were performed trans-radial approach) and TFI group (n = 253, PCIs were
      performed trans-femoral approach). Efficacy and safety data were compared between
      the two groups. RESULTS: There were no differences in success rate of stenting,
      procedure time, contrast amount, rates of contrast-induced nephropathy, major
      adverse cardiovascular events during hospitalization, at one year follow up and
      at two years follow up. Lower vascular complications were associated with TRI
      approach[ 17.9% (42/253) vs. 26.9% (68/253) , P < 0.05], especially in TIMI major
      bleeding ratio [1.3% (3/235) vs. 4.7% (12/253) , P < 0.05], TIMI minor bleeding
      [5.1% (12/235) vs. 15.8% (40/253) , P < 0.01], and time lying in bed [3.6 (2.8
      4.2)h vs. 24.4 (24.0-25.1)h, P < 0.01] and hospitalization [3.0 (3.0-4.0)d vs.
      5.0 (5.0-6.0)d, P < 0.01], and higher rates of crossover approach were associated
      with TRI [11.5% (27/235) vs. 2.0(5/253) , P < 0.01]. CONCLUSION: TRI is as
      feasible, safe and effective as TFI in elderly patients during short-term and
      long-term follow up, and TRI is associated with higher rates of crossover
      approach.

PMID- 24331800
TI  - [The relationship between hyperuricemia and contrast-induced nephropathy in
      patients with chronic kidney disease undergoing percutaneous coronary
      intervention].
AB  - OBJECTIVE: To investigate the relationship between hyperuricemia and contrast
      induced nephropathy (CIN) in patients with chronic kidney disease (CKD)
      undergoing percutaneous coronary intervention (PCI). METHODS: A total of 446
      consecutive patients with CKD undergoing PCI in Guangdong general hospital were
      enrolled in this study. Patients were divided into hyperuricemic group (n = 205)
      and normouricemic group (n = 241).Hyperuricemia was defined as serum uric acid >
      420 umol/L for male, > 357 umol/L for female. CIN was defined as >= 44.2 umol/L
      or >= 25% increase from baseline Serum creatinine within 48-72 hours after
      contrast medium exposure, and that was not attributable to other causes.In
      hospital incidences of CIN and the major adverse cardiac events were compared
      between the two groups. The relationship between the incidence of CIN and
      hyperuricemia was evaluated by multivariate logistic regression analysis.
      RESULTS: CIN occurred in 16.6% (74/446) of patients, and incidence of CIN was
      significantly higher in the hyperuricemic group than in the normouricemic group
      [23.9% (49/446) vs. 10.4% (25/446) , P = 0.000]. Patients who developed CIN had
      higher in hospital mortality [14.9% (11/74) vs. 1.3% (5/372), P = 0.000]. Need
      for renal replacement therapy, acute heart failure, intra-aortic balloon pump use
      and the hypotension after PCI were significantly higher in the hyperuricemic
      group compared with normouricemic group (P < 0.01 or P < 0.05) . Multivariate
      analysis indicates that hyperuricemia (OR = 1.9, 95%CI:1.1-3.5, P = 0.037), age >
      75 years (OR = 3.2, 95%CI:1.8-5.7, P = 0.000) , emergent PCI (OR = 2.9, 95%CI:1.6
      5.1, P = 0.000) and anemia (OR = 2.1, 95%CI:1.2-3.8, P = 0.012) were predictors
      of CIN in patients with CKD. CONCLUSION: Hyperuricemia is the independent risk
      predictor of CIN in patients with CKD undergoing PCI.

PMID- 24331801
TI  - [Safety and efficacy of percutaneous transcatheter closure of atrial septal
      defect under transesophageal echocardiography guidance in children].
AB  - OBJECTIVE: To assess the safety and effectiveness of percutaneous transcatheter
      closure of atrial septal defect (ASD) under transesophageal echocardiography
      (TEE) guidance in children. METHODS: The study included 20 cases of patients with
      ASD. The patients were (4.2 +/- 1.2) years old and the mean body weights were
      (18.2 +/- 4.2) kg. The diameter of ASD before closure was (13.4 +/- 3.3) mm . All
      procedures were guided under TEE. Procedure success was evaluated by TEE
      immediately after procedure. RESULTS: Closure devices were successfully implanted
      in all 20 patients under TEE guidance. The diameter of closure devices was 14-26
      mm. There were no procedure related complications. The ventilation time was (2.9
      +/- 0.8)h and the hospitalization time was (3.2 +/- 0.7) days. CONCLUSION: TEE
      guided percutaneous transcatheter closure is safe and effective for patients with
      ASD and avoids the radiation damages.

PMID- 24331802
TI  - [Effects of noninvasive positive pressure ventilation on patients with arrhythmia
      complicated by sleep apnea syndrome].
AB  - OBJECTIVE: To investigate the clinical efficacy of noninvasive positive pressure
      ventilation (NPPV) in treatment of patients with arrhythmia complicated by sleep
      apnea syndrome (SAS). METHODS: One hundred and thirty-five arrhythmia patients
      with polysomnography diagnosed SAS were randomly divided into NPPV group (69
      cases) and control group (66 cases), the NPPV group was treated with standard
      medications and NPPV, and the control group was treated with standard
      medications. SAS related parameters were compared between the groups after 3
      months therapy. RESULTS: (1) Epworth sleepiness scale (ESS) score, apnea-hypopnea
      index (AHI) and arousal index were significantly lower (8.25 +/- 5.41 vs.4.08 +/-
      3.43, 39.95 +/- 7.32 vs. 4.71 +/- 1.80 and 39.69 +/- 4.40 vs. 15.20 +/- 2.05, P <
      0.01) while not rapid eye movement (NREM) III and rapid eye movement stage of
      sleep time and lowest pulse oxygen saturation (LSaO2) were significantly higher
      in NPPV group than in control group [(4.53 +/- 2.10)% vs. (16.78 +/- 2.59)%,(8.37
      +/- 1.380)% vs. (15.25 +/- 1.41)%, (77.15 +/- 6.72)% vs. (93.35 +/- 2.03)%, P <
      0.01] after 3 months therapy. (2) Incidence of Sinus bradycardia, sinus
      tachycardia, sinus arrest, atrial premature beats, ventricular premature beats,
      paroxysmal atrial tachycardia, paroxysmal ventricular tachycardia, atrial
      fibrillation, II-III degree atrioventricular block, ST-T segment changes were
      reduced from 57.4%, 44.4%, 7.4%, 20.4%, 13.0%, 36.5%, 12.0%, 8.3%, 37.0%, 53.7%
      to 4.6%, 1.9%,0.0%, 3.7%, 2.8%, 7.0%, 0.9%, 0.0%, 1.9%, 4.6% (all P < 0.05) and
      the total number of arrhythmias happened at night were significantly lower (all P
      < 0.05) while the heart rate variability (HRV) were significantly higher (P <
      0.01) in NPPV group than in control group; AHI was positively while LSaO2 was
      negatively correlated with the total night arrhythmia number (P < 0.01).
      CONCLUSION: Noninvasive positive pressure ventilation is an effective therapy
      strategy for treating patients with arrhythmia complicated by sleep apnea
      syndrome.

PMID- 24331803
TI  - [Analysis of influencing factors on circadian blood pressure of hypertensive
      patients with obstructive sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To investigate the effect of obesity, arousal, hypoxia and sympathetic
      activation on the circadian blood pressure of hypertensive patients with
      obstructive sleep apnea-hypopnea syndrome. METHODS: Polysomnography (PSG) was
      performed in 436 hypertensive patients complaining of snoring, daytime
      sleepiness, lips cyanosis, hyperhemoglobinemia of unknown etiology, or with
      refractory hypertension. Hypertensive subjects were divided into four groups
      according to apnea-hypopnea index (AHI): hypertensive with mild obstructive sleep
      apnea-hypopnea syndrome (OSAHS) (n = 131), hypertensive with moderate OSAHS (n =
      95), hypertensive with severe OSAHS (n = 95) and hypertensive without OSAHS as
      control group (n = 115). The ambulatory blood pressure monitoring (ABPM), PSG,
      urine electrolyte, and urine vanillylmandelic acid (VMA) were compared among
      groups. Factor analysis was employed to identify common factors related to the
      alterations of circadian blood pressure. Multiple linear regression analysis was
      used to analyze the influencing factors of the observed variables. RESULTS: There
      were significant differences among groups in age, neck circumference and waist
      circumference(P < 0.001). In severe group, 24 hour average systolic blood
      pressure (24 hSBP)[ (137.0 +/- 16.8) mm Hg vs.(131.3 +/- 11.9)mm Hg, (131.3 +/-
      13.2)mm Hg (1 mm Hg = 0.133 kPa)], daytime systolic blood pressure (day-SBP)
      [(140.8 +/- 16.8) mm Hg vs. (135.7 +/- 11.9) mm Hg, (135.3 +/- 13.5) mm Hg]and
      night systolic blood pressure (night-SBP)[ (130.9 +/- 17.0) mm Hg vs.(124.5 +/-
      14.0 )mm Hg, (124.3 +/- 13.2) mm Hg] were significantly higher than those of
      control or mild OSAS groups (P < 0.01). Factor analysis showed that body mass
      (BM), life style, urine electrolyte, age and course of disease (ACD) were the
      common factors influencing circadian blood pressure. OSAHS was correlated with
      declining percentage of SBP (beta = -0.128, P < 0.01) and declining percentage of
      DBP (beta = -0.126, P < 0.01). The contribution according to priority was ACD >
      OSAHS > BM for declining percentage of SBP (beta = -0.148, P = 0.002;beta = 
      0.128, P = 0.007;beta = 0.099, P = 0.035), OSAHS > ACD > BM for declining
      percentage of DBP(beta = -0.126, P = 0.008;beta = -0.105, P = 0.026;beta = 0.097,
      P = 0.042). CONCLUSION: OSAHS, ACD and BM are the independent risk factors
      contributing to the alterations of circadian blood pressure in hypertensive
      patients with obstructive sleep apnea-hypopnea syndrome.

PMID- 24331796
TI  - Sensory aspects of movement disorders.
AB  - Movement disorders, which include disorders such as Parkinson's disease,
      dystonia, Tourette's syndrome, restless legs syndrome, and akathisia, have
      traditionally been considered to be disorders of impaired motor control resulting
      predominantly from dysfunction of the basal ganglia. This notion has been revised
      largely because of increasing recognition of associated behavioural, psychiatric,
      autonomic, and other non-motor symptoms. The sensory aspects of movement
      disorders include intrinsic sensory abnormalities and the effects of external
      sensory input on the underlying motor abnormality. The basal ganglia, cerebellum,
      thalamus, and their connections, coupled with altered sensory input, seem to play
      a key part in abnormal sensorimotor integration. However, more investigation into
      the phenomenology and physiological basis of sensory abnormalities, and about the
      role of the basal ganglia, cerebellum, and related structures in somatosensory
      processing, and its effect on motor control, is needed. 

PMID- 24331804
TI  - [Association between serum homocysteine and in-hospital death in patients with
      acute pulmonary embolism].
AB  - OBJECTIVE: To explore the association between serum homocysteine (Hcy) level and
      in-hospital death in patients with acute pulmonary embolism. METHODS: A total of
      186 acute pulmonary embolism patients [ (66.8 +/- 12.7) years, 89 male]
      hospitalized in our department between June 2008 and June 2011 were included in
      this prospective study. Patients were divided into high Hcy group (Hcy >= 15.2
      umol/L, n = 95) and low Hcy group (Hcy < 15.2 umol/L, n = 91). Patients were
      followed-up for 1 year for the incidence rate of early death associated with
      acute pulmonary embolism. The Cox proportional hazard model was used to analyze
      the relationship between serum Hcy level and early death in acute pulmonary
      embolism patients. RESULTS: Patients were hospitalized for 1-37 days [(10 +/- 6)
      days]. In-hospital death rate was 14.5% (27/186) and was significantly higher in
      high Hcy group than in low Hcy group [25.3% (24/95) vs. 3.3% (3/91) , P = 0.001].
      Univariate Cox regression analysis indicated that admission heart rate, oxygen
      saturation, enlargement of right ventricle, Hcy >= 15.2 umol/L, serum creatinine
      level, peak TnT level and deep venous thrombosis (P < 0.05) were independent risk
      factors for in-hospital death. Multivariate Cox regression analysis showed that
      Hcy >= 15.2 umol/L (HR = 4.10, 95%CI:3.00-4.98, P = 0.017), admission heart rate
      (HR = 1.10, 95%CI:1.01-1.20, P = 0.031) , deep venous thrombosis (HR = 1.65,
      95%CI:1.45-1.76, P = 0.034) and age (HR = 1.10, 95%CI:1.02-1.19, P = 0.010) were
      independent predictors of in-hospital death for acute pulmonary embolism
      patients. One-year follow up was finished in 142 patients (89.3%). There were 19
      deaths ( 5 due to repeat pulmonary embolism, 4 due to decompensated respiratory
      and /or cardiac diseases, 6 due to malignant tumors, 2 due to fatal bleeding and
      2 due to pneumonia) . Death rate was similar between the two groups during follow
      up. CONCLUSION: Higher serum homocysteine is an independent for in-hospital death
      for patients with acute pulmonary embolism.

PMID- 24331805
TI  - [Association between degree of pulmonary artery hypertension and cardiac
      structural and functional changes in chronic high altitude heart disease
      patients].
AB  - OBJECTIVE: To compare the cardiac structural and functional changes in high
      altitude heart disease (HAHD) patients with various grade of pulmonary artery
      hypertension (PAH). METHODS: Pulmonary artery systolic pressure (PASP) was
      evaluated by Doppler echocardiography in 100 patients with HAHD and patients were
      divided into 3 groups: mild (PASP: 30-49 mm Hg), moderate (PASP: 50-69 mm Hg) and
      severe (PASP >= 70 mm Hg) PAH and 50 patients without organic heart disease
      served as control group. Data on heart structure and function, heart rhythm and
      whole blood NT-proBNP were compared among groups. RESULTS: Right ventricular free
      wall was significantly thicker in moderate and severe PAH groups than in the
      control group [(5.10 +/- 2.23) mm, (7.00 +/- 2.29 ) mm vs.(3.70 +/- 0.92)mm, P <
      0.05], and in the severe PAH group than in mild and moderate PAH groups [ (7.00
      +/- 2.29) mm vs.(4.58 +/- 1.80) mm, (5.10 +/- 2.23) mm, all P < 0.05] and which
      was similar between the mild PAH group and the control group. Right ventricular
      inter diameter and right ventricular outflow tract inter diameter were
      significantly increased in all HAHD groups compared to the control group (all P <
      0.01), and were also significantly increased in moderate and severe PAH groups
      than in the mild PAH group (P < 0.01). Thickness of interventricular septum was
      also significantly increased in HAHD patients than control group and in moderate
      and severe PAH groups than in moderate PAH group. Left atrium anterior-posterior
      diameter was significantly increased in HAHD patients than in control group and
      was similar among HAHD patients with various degree of PAH. Left ventricular
      ejection fraction (LVEF) was remarkably decreased in all HAHD groups than in the
      control group (P < 0.05) , moreover, LVEF was remarkably decreased in the
      moderate PAH group than in the mild PAH group (P < 0.05) . EF was similar between
      severe PAH group and moderate PAH group (P > 0.05) . There was no significant
      correlation between lgPASP and EF (R = -0.103, P = 0.298) . Compared with the
      control group, the incidences of decompensated heart failure and arrhythmia were
      remarkably increased in HAHD patients (P < 0.05) . The level of whole blood NT
      proBNP increased in proportion to increasing PASP in HAHD patients (P < 0.05).
      CONCLUSION: Increased PASP correlates with whole blood NT-proBNP and is an
      important determinant affecting the right ventricular structure and left and
      right ventricular function in HAHD patients.

PMID- 24331806
TI  - [A survey on knowledge of recommended heart failure guidelines among Chinese
      physicians].
AB  - OBJECTIVE: To obtain the knowledge status on recommended heart failure (HF)
      guidelines among Chinese physicians. METHODS: Questionnaire on heart failure
      including 20 multiple choice questions and 10 fill in the blank questions was
      designed based on the Chinese guidelines for the diagnosis and treatment of
      chronic heart failure in 2007 and the Chinese guidelines for the diagnosis and
      treatment of acute heart failure in 2010. The rate of correct answer for each
      item was calculated and compared among physicians specialized for cardiovascular
      diseases and not. RESULTS: The Questionnaire was completed in 400 physicians,
      including 208 physician specialized for cardiovascular disease and 192 physicians
      not specialized in cardiovascular disease. The rate of correct answer for 20
      multiple choice questions was lower than 60% in 8 questions, 60%-80% in 8
      questions, higher than 80% in 4 questions. The rate of correct answers for 10
      fill in the blank questions focusing on the aimed dosage of 10 ACEI/ARB/beta
      blockers was 49%. The 8 multiple choice questions with correct answer rate <60%
      are detailed items of myocardial remodeling, symptoms suggestive of HF, diagnosis
      tools for patients with suspected HF, the AHA stages of heart failure, the
      Forrester's hemodynamic classes of acute heart failure, the goals of ACEI/ARBs
      treatment in patients with HF, names of heart diseases which might benefit from
      ACEI/ARBs treatment defined by evidenced based medicine, and detailed application
      methods of ACEI/ARBs and beta-blockers for HF patients. In general, the rate of
      correct answer was significantly higher in physicians specialized for
      cardiovascular disease compared physicians not specialized for cardiovascular
      disease. CONCLUSION: There is a considerable knowledge gap on the Chinese
      guidelines for the diagnosis and treatment of chronic heart failure and the
      Chinese guidelines for the diagnosis and treatment of acute heart failure among
      Chinese physicians. Efforts must be made to educate physicians to improve their
      knowledge and improve HF patient care.

PMID- 24331807
TI  - [Angiotensin-converting enzyme 2 gene transfer attenuates neointimal formation
      after carotid artery ischemia-reperfusion injury in rats].
AB  - OBJECTIVE: To explore the effects of lentiviral recombinant angiotensin
      converting enzyme 2 (LV-ACE2) gene transfer on the neointimal formation after
      carotid artery ischemia-reperfusion injury (IRI) and related mechanisms. METHODS:
      IRI was induced in SD rats through the carotid artery clipping and rats were
      divided into IRI, IRI+LV-GFP, IRI+LV-ACE2, IRI+ paclitaxel groups (n = 10 each).
      Sham operated rats serve as normal control. Four weeks later, neointimal
      formation was observed on HE stained carotid artery sections. The protein
      expression of ACE2, alpha-SM-actin, CD31, AT1R and P-ERK were detected by
      immunohistochemistry. RESULTS: (1) Carotid artery neointimal hyperplasia was
      readily shown in IRI group [I/M: 1.517 +/- 0.151 (4 weeks later) vs. 0.011 +/-
      0.004 (Sham), P < 0.01], which was significantly reduced in IRI+LV-ACE2 (0.71 +/-
      0.17) and IRI+ paclitaxel (0.89 +/- 0.21) groups. (2) The growth of vascular
      smooth muscle cells and neovascularization were also significantly inhibited in
      IRI+LV-ACE2 group and the expression of alpha-SM-actin (5 843 +/- 839 vs. 12 648
      +/- 1 760, P < 0.01) and CD31 [(12.40 +/- 4.01)/mm(2) vs. (96.20 +/-
      17.79)/mm(2), P < 0.01], AT1R (1 219 +/- 175 vs. 4 861 +/- 545, P < 0.01) and P
      ERK1/2 phosphorylation (1 040 +/- 215 vs. 2 938 +/- 286, P < 0.01) in the
      neointimal of the injury arteries in IRI+LV-ACE2 group were significantly
      downregulated compared to IRI group. CONCLUSION: This data suggest that ACE2 gene
      overexpression is able to attenuate neointimal formation after ischemia
      reperfusion injury possibly through downregulating AT1 receptor expression and
      signal pathway of ERK1/2 phosphorylation.

PMID- 24331808
TI  - [The effect of recombinant human interleukin-2 activated natural killer cells on
      angiogenesis and cardiac function in rats with experimental myocardial
      infarction].
AB  - OBJECTIVE: To investigate the effect of recombinant human interleukin-2 (rhIL-2)
      activated natural killer cells (rhIL-2-NK) on angiogenesis and cardiac function
      of rats with myocardial infarction (MI). METHODS: Natural killer cells (NKs) were
      isolated and activated by rhIL-2 in vitro. Untreated NKs were used as the
      control, the killing capacity of rhIL-2-NK were evaluated with cytotoxicity
      assay. Cardiac microvascular endothelial cells (CMECs) were cocultured with rhIL
      2-NK. One hour after MI, rats were randomly divided into rhIL-2-NK group, NK
      group and blank control group and NK, rhIL-2-NK and PBS were injected directly in
      the infracted myocardium. At the 0, 1(st), 3(rd), 5(th), 7(th) and 20(th)th day
      after MI, the mRNA expression of monocyte chemotactic protein-1 (MCP-1), Tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) were was detected by q
      PCR essay. At the end of the therapy, the platelet endothelial cell adhesion
      molecule-1(CD31) and vascular endothelial growth factor (VEGF) were evaluated
      through immunohistochemical assay, and the cardiac function observed with
      echocardiography, homodynamic measurements. RESULTS: The NKs were isolated
      successfully and the CMEC were proliferated remarkably by coculturing with rhIL-2
      NK (P < 0.01). The mRNA expression of MCP-1, TNF-alpha, CD31 and rhIL-2, VEGF
      were significantly upregulated in rhIL-2-NK group than in the PBS control group
      (P < 0.01). Four weeks after operation, LVEF was significantly higher in rhIL-2
      NK group than in the PBS control group [(77.56 +/- 15.67)% vs. (41.47 +/-
      12.21)%, P < 0.05)] and histomorphology assay revealed that the density of
      microvascular endothelial (MVD) of rhIL-2-NK group was significantly higher than
      that of PBS control group (17.35 +/- 1.82 vs. 4.76 +/- 0.92, P < 0.01).
      CONCLUSIONS: Myocardial injection of rhIL-2-NK could promote angiogenesis and
      improve cardiac function in MI rats.

PMID- 24331809
TI  - [Effect of hypoxia inducible factor-1alpha on thermotolerance against hyperthemia
      induced cardiomyocytes apoptosis].
AB  - OBJECTIVE: To investigate the expression changes and effects of hypoxia inducible
      factor-1alpha (HIF-1alpha) on non-lethal high temperature induced thermotolerance
      and its role on thermotolerance protection. METHODS: H9c2 cardiomyocytes were
      cultured and pretreated with the HIF-1alpha inhibitor YC-1, the cells were then
      subjected to normal temperature (37  degrees C), thermotolerance induction (40 
      degrees C, 3 h), or hyperthermia (43  degrees C, 2 h). The cells were divided
      into 8 groups (n = 3 each): normal temperature control group; thermotolerance
      group; thermotolerance/hyperthermia group; hyperthermia group; DMSO+normal
      temperature group; YC-1+thermotolerance group; YC-1+thermotolerance/hyperthermia
      group; YC-1+hyperthermia group. Cell apoptotic rate was assessed by flow
      cytometry. Western blot was used to detect the expression of HIF-1alpha and
      caspase-3. RESULTS: Flow cytometry results showed that apoptosis rate was similar
      between control group and thermotolerance group, between DMSO+normal temperature
      group and YC-1+thermotolerance group, between YC-1+thermotolerance/hyperthermia
      group and YC-1+hyperthermia group, but was significantly higher in hyperthermia
      group [(17.35 +/- 1.07)%] than in control group [(7.52 +/- 1.55)%, P < 0.01]
      which was partly reduced in thermotolerance/hyperthermia group [(12.58 +/-
      1.97)%, P < 0.01 vs. thermotolerance group]. Cell apoptosis rate of YC
      1+thermotolerance/hyperthermia group (23.75 +/- 1.92)% was significantly higher
      than that of thermotolerance/hyperthermia group [(12.58 +/- 1.97)%, P < 0.01],
      and in YC-1+hyperthermia group [(24.89 +/- 1.83)%] than in hyperthermia group
      [(17.35 +/- 1.07)%, P < 0.01]. HIF-1alpha expression was obviously upregulated in
      thermotolerance cells compared with control cells, in
      thermotolerance/hyperthermia cells than in hyperthermia cells, in YC
      1+thermotolerance group, YC-1+thermotolerance/hyperthermia group and YC
      1+hyperthermia group than in DMSO group (all P < 0.05). Caspase-3 expression was
      similar between control group and thermotolerance group, but was significantly
      lower in thermotolerance/hyperthermia group than in hyperthermia group (P <
      0.05), significantly higher in YC-1+thermotolerance group, YC
      1+thermotolerance/hyperthermia group and YC-1+hyperthermia group than in DMSO
      group (all P < 0.05) and significantly higher in YC
      1+thermotolerance/hyperthermia group than in thermotolerance/hyperthermia group
      (P < 0.01) and in YC-1+hyperthermia group than in hyperthermia group (P < 0.01).
      CONCLUSION: Non-lethal high temperature induced thermotolerance can reduce heat
      stress-induced cardiomyocytes apoptosis rate via upregulating the expression of
      HIF-1alpha and inhibiting caspase-3 signalling pathways.

PMID- 24331810
TI  - [An epidemiology study on hypertension in the Zhuang nationality village from the
      Guangxi Zhuang Autonomous Region].
AB  - OBJECTIVE: To observe the risk factors and prevalence status of hypertension at
      the Guangxi Zhuang-rural region. METHODS: Through cross-sectional survey, Xinlan
      village (Ethnic-Zhuang tribe village) in Liangqing District of Nanning was chosen
      as survey site. Select Zhuang-ethnic villagers (age >= 18 years, living time >= 6
      months per year) as survey subjects. Questionnaire survey and examinations
      including blood pressure measurement, blood tests, and urine test were made by
      trained medical professionals. Multivariate logistic regression analysis was used
      to analyze the risk factors of hypertension. RESULTS: Complete data were obtained
      in 2036 residents. The hypertension prevalence rate was 11.6% (237/2036) [12.5%
      (110/883) for male, 11.0% (127/1153) for female], adjusted prevalence rate was
      10.7% (11.3% for male, 10.4% for female) based on the population of Guangxi in
      2010. Hypertension awareness rate was 36.3% (86/237) , therapy rate was 22.8%
      (54/237) , and control rate was 11.0% (26/237) . Multivariate logistic regression
      analysis showed that age (OR = 1.06, 95%CI:1.05-1.08, P < 0.01), alcohol drinking
      habit (OR = 1.92, 95%CI:1.25-2.95, P < 0.01), high salt diet(OR = 1.48,
      95%CI:1.04-2.10, P < 0.05), diabetes(OR = 7.03, 95%CI:1.94-25.44, P < 0.01),
      obesity(OR = 1.20, 95%CI: 1.15-1.25, P < 0.01) and hypertriglyceridemia(OR =
      1.12, 95%CI:1.03-1.22, P < 0.01) were risk factors for hypertension in this
      cohort. CONCLUSIONS: Prevalence rate is slightly lower in adult of the Guangxi
      Zhuang-rural areas than national or Guangxi Zhuang Autonomous Region levels, but
      hypertension awareness, therapy and control rates in this cohort are not
      satisfactory. Targeted strategies are needed to improve the prevention and
      therapy of hypertension in this region.

PMID- 24331811
TI  - [Meta analysis on the association of CYP11B2 gene polymorphism and essential
      hypertension in Chinese Han population].
AB  - OBJECTIVE: To explore the association between CYP11B2 gene polymorphism and
      essential hypertension, blood pressure level in Chinese Han population by meta
      analysis. METHODS: After searching database, the research quality was quantified
      according to NOS. Genetic model, heterogeneity, publication bias, overall
      OR/standardized mean difference (SMD) and 95%CI were explored by Stata, 19
      studies including 9249 subjects were included in this meta-analysis. RESULTS:
      Compared to control group, OR(95%CI) of CC vs. TT, CT vs. TT, CC vs. CT in
      essential hypertensive patients were 1.022(95%CI: 0.879-1.190), 1.108 (95%CI:
      0.951-1.291), 1.050(95%CI:0.995-1.109), respectively; SMD (95%CI) was 0.315
      (0.066-0.565, P < 0.05) for systolic pressure derived CC vs. TT, and 0.088 (0.014
      0.162, P < 0.05) for CT vs. TT CONCLUSION: Individuals with -344C CYP11B2 allele
      are at higher risk of increased systolic blood pressure, but there is no evidence
      showing association between CYP11B2 polymorphism and susceptibility of essential
      hypertension in Chinese Han population.

PMID- 24331812
TI  - [Transcatheter valve-in-valve implantation for failed bioprosthetic aortic valve:
      a case report].

PMID- 24331813
TI  - [Three cases of rare atrial masses].

PMID- 24331814
TI  - [Recent progress on tricuspid regurgitation].

PMID- 24331815
TI  - [Research progress on atherosclerotic plaque regression].

PMID- 24331816
TI  - [Progress on genetic research on familial congenital heart disease].

PMID- 24331818
TI  - Burden of human papillomavirus infections and related diseases in the extended
      Middle East and North Africa region.
AB  - In this chapter, we present the available information on the burden of human
      papillomavirus (HPV)-related cancers (cancers of the cervix, anogenital cancers,
      and cancers of the oral cavity and pharynx), as well as available data on the
      prevalence and distribution of HPV types in women with and without cervical
      cancer, for the countries of the Extended Middle East and North Africa region
      (EMENA). The EMENA region is characterized by societies that share similar
      cultures and religions and that are considered to have a more conservative sexual
      behaviour compared to Western societies. The incidence of cervical cancer is
      estimated to be relatively low, although it is difficult to assess precisely
      because systematic and national cancer registries are lacking in many countries
      of the EMENA region. In these countries, nationwide programs of cervical cancer
      screening do not exist or are based on a limited opportunistic cytology-based
      screening, which often lacks quality assurance. The incidence of anogenital
      cancers other than cervix is very low. The incidence of cancers of the oral
      cavity and pharynx is relatively high in some countries, particularly in
      Pakistan. Relatively low levels of HPV prevalence have been observed in the
      several surveys conducted in the EMENA region, although only few young women were
      included in these studies. Possible changes in lifestyle and sexual behaviour in
      younger generations might, however, change this scenario. Thus, improving the
      information on the burden of HPV-related cancers and on the HPV prevalence in the
      general population is essential to develop a comprehensive intervention policy
      for future management of cervical cancer in this area. This article forms part of
      a regional report entitled "Comprehensive Control of HPV Infections and Related
      Diseases in the Extended Middle East and North Africa Region" Vaccine Volume 31,
      Supplement 6, 2013. Updates of the progress in the field are presented in a
      separate monograph entitled "Comprehensive Control of HPV Infections and Related
      Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24331819
TI  - Sexuality and sexual health: constructs and expressions in the extended Middle
      East and North Africa.
AB  - The extended Middle East and North Africa (EMENA) region is the world region with
      the second youngest population, where globalization, migration, information
      technology, and political changes are contributing to the shaping of sexuality
      and sexual behaviors. Understanding the various sociocultural, demographic and
      public health dimensions of sexual and reproductive health of young people is
      fundamental to understanding the pattern of sexual behavior and the burden of
      sexually transmitted infections (STIs), including human papillomavirus-related
      diseases. New norms and forms of marriage have emerged to accommodate the
      changing trends in sexual behavior of premarital and extra-marital sex, as well
      as reports of increased prevalence of premarital penetrative and non-penetrative
      sexual behavior. Despite these trends, the burden of sexual illnesses remains low
      and is estimated at 7% of the general population being infected with curable
      STIs. Other STIs, such as herpes simplex virus 2, are also prevalent. The
      existing policies and health systems remain short of promoting youth reproductive
      and sexual health. Efforts should address establishing national preventive
      programmes, such as screening for STIs, primary prevention, comprehensive
      sexuality education, as well as youth-friendly services. This article forms part
      of a regional report entitled "Comprehensive Control of HPV Infections and
      Related Diseases in the Extended Middle East and North Africa Region" Vaccine
      Volume 31, Supplement 6, 2013. Updates of the progress in the field are presented
      in a separate monograph entitled "Comprehensive Control of HPV Infections and
      Related Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24331820
TI  - Overview of cervical cancer screening practices in the extended Middle East and
      North Africa countries.
AB  - National Organized Cervical Cancer Screening (NOCCS) programs are lacking in most
      of the "Extended Middle East and North Africa" (EMENA) countries. Consequently,
      most cervical cancers are diagnosed late and are associated with high mortality.
      In fact, in most of these countries, national mortality data are unknown due to
      the absence of population-based mortality registries. Most countries of the EMENA
      practice more or less limited opportunistic, cytology-based, screening tests,
      which often lack quality assurance and follow-up care. A few countries, within
      the initiation of a National Cancer Control Plan, have just started to implement
      organized screening programs using, for cervical cancer detection, visual
      inspection with acetic acid (Morocco) or cytology (Turkey). Moreover, most
      countries of the EMENA lack national guideline, as well as resources for the
      management of abnormal cytologic screening (or any other screening test). The
      main obstacle for the implementation of NOCCS is a lack of political
      understanding to support such public health programs and provide the necessary
      resources. Other obstacles that hinder the participation of women in cervical
      screening include a lack of knowledge of the disease, socio-religious and
      cultural barriers, and geographic and economic difficulties in accessing medical
      services. These countries are already convinced that prevention of cervical
      cancers in women who have cervical intraepithelial neoplasia is possible through
      various screening and treatment algorithms, but most countries still need to
      invest in well organized programs that can reduce cervical cancer incidence and
      mortality in women. This article forms part of a regional report entitled
      "Comprehensive Control of HPV Infections and Related Diseases in the Extended
      Middle East and North Africa Region" Vaccine Volume 31, Supplement 6, 2013.
      Updates of the progress in the field are presented in a separate monograph
      entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine
      Volume 30, Supplement 5, 2012. 

PMID- 24331817
TI  - Comprehensive control of human papillomavirus infections and related diseases.
AB  - Infection with human papillomavirus (HPV) is recognized as one of the major
      causes of infection-related cancer worldwide, as well as the causal factor in
      other diseases. Strong evidence for a causal etiology with HPV has been stated by
      the International Agency for Research on Cancer for cancers of the cervix uteri,
      penis, vulva, vagina, anus and oropharynx (including base of the tongue and
      tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide,
      4.8% were attributable to HPV infection, with substantially higher incidence and
      mortality rates seen in developing versus developed countries. In recent years,
      we have gained tremendous knowledge about HPVs and their interactions with host
      cells, tissues and the immune system; have validated and implemented strategies
      for safe and efficacious prophylactic vaccination against HPV infections; have
      developed increasingly sensitive and specific molecular diagnostic tools for HPV
      detection for use in cervical cancer screening; and have substantially increased
      global awareness of HPV and its many associated diseases in women, men, and
      children. While these achievements exemplify the success of biomedical research
      in generating important public health interventions, they also generate new and
      daunting challenges: costs of HPV prevention and medical care, the implementation
      of what is technically possible, socio-political resistance to prevention
      opportunities, and the very wide ranges of national economic capabilities and
      health care systems. Gains and challenges faced in the quest for comprehensive
      control of HPV infection and HPV-related cancers and other disease are summarized
      in this review. The information presented may be viewed in terms of a reframed
      paradigm of prevention of cervical cancer and other HPV-related diseases that
      will include strategic combinations of at least four major components: 1) routine
      introduction of HPV vaccines to women in all countries, 2) extension and
      simplification of existing screening programs using HPV-based technology, 3)
      extension of adapted screening programs to developing populations, and 4)
      consideration of the broader spectrum of cancers and other diseases preventable
      by HPV vaccination in women, as well as in men. Despite the huge advances already
      achieved, there must be ongoing efforts including international advocacy to
      achieve widespread-optimally universal-implementation of HPV prevention
      strategies in both developed and developing countries. This article summarizes
      information from the chapters presented in a special ICO Monograph 'Comprehensive
      Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5,
      2012. Additional details on each subtopic and full information regarding the
      supporting literature references may be found in the original chapters. 

PMID- 24331821
TI  - Prospects and challenges in the introduction of human papillomavirus vaccines in
      the extended Middle East and North Africa region.
AB  - The development of effective and safe human papillomavirus (HPV) vaccines
      provides a great opportunity to prevent a devastating disease, cervical cancer,
      and a host of other related diseases. However, the introduction of these vaccines
      has been slow in the Extended Middle East and North Africa (EMENA) region. Only
      one country has introduced the vaccine and few countries plan HPV vaccine
      introduction in the coming 5 years. Several factors influence the slow uptake in
      the region, including financial constraints, weak infrastructure for adolescent
      vaccine delivery, competition with high priority vaccines, and lack of reliable
      data on the burden of HPV disease. Other barriers include cultural and religious
      sensitivities, as the vaccines are offered to prevent a sexually transmitted
      disease in young girls. Recommendations to enhance HPV vaccine introduction in
      EMENA countries include establishing a regional joint vaccine procurement
      program, enhancing the adolescent vaccination platform, documenting the burden of
      cervical cancer, strengthening local National Immunization Technical Advisory
      Groups and designing Information, Education and Communication material that
      address cultural concerns. This article forms part of a regional report entitled
      "Comprehensive Control of HPV Infections and Related Diseases in the Extended
      Middle East and North Africa Region" Vaccine Volume 31, Supplement 6, 2013.
      Updates of the progress in the field are presented in a separate monograph
      entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine
      Volume 30, Supplement 5, 2012. 

PMID- 24331822
TI  - Model-based impact and cost-effectiveness of cervical cancer prevention in the
      Extended Middle East and North Africa (EMENA).
AB  - To date, no studies have evaluated the cost-effectiveness of human papillomavirus
      (HPV) vaccination in countries in the Extended Middle East and North Africa
      (EMENA) region. We synthesized population and epidemiologic data for 20 EMENA
      countries using a model-based approach to estimate averted cervical cancer cases
      and deaths, disability-adjusted life years (DALYs) and cost-effectiveness ratios
      (I$ [international dollars] per DALY averted) associated with HPV vaccination of
      pre-adolescent girls. We utilized additional epidemiologic data from Algeria,
      Lebanon, and Turkey to evaluate select cervical cancer screening strategies
      either alone or in combination with vaccination. Results showed that pre
      adolescent vaccination of five consecutive birth cohorts at 70% coverage has the
      potential to prevent over 180,000 cervical cancer cases. Cases averted varied by
      country, largely due to differences in cancer burden and population size; 69% of
      cases averted occurred in the three GAVI-eligible countries in EMENA. Despite the
      low cervical cancer incidence in EMENA, we found that HPV vaccination was cost
      effective using a threshold of each country's gross domestic product per capita
      (a common metric for evaluating cost-effectiveness) in all but five countries at
      a cost per vaccinated girl of I$25 ($5 per dose). However, cost-effectiveness
      diminished with increasing vaccine cost; at a cost of I$200 per vaccinated girl,
      HPV vaccination was cost-effective in only five countries. When the cost per
      vaccinated girl exceeded I$50 in Lebanon and Turkey and I$150 in Algeria,
      screening alone was most attractive. We identified opportunities to improve upon
      current national screening guidelines, involving less frequent screening every 3
      5 years. While pre-adolescent HPV vaccination promises to be a cost-effective
      strategy in most EMENA countries at low costs, decision makers will need to
      consider many other factors, such as affordability, acceptability, feasibility,
      and competing health priorities, when making decisions about cervical cancer
      prevention. This article forms part of a regional report entitled "Comprehensive
      Control of HPV Infections and Related Diseases in the Extended Middle East and
      North Africa Region" Vaccine Volume 31, Supplement 6, 2013. Updates of the
      progress in the field are presented in a separate monograph entitled
      "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30,
      Supplement 5, 2012. 

PMID- 24331823
TI  - Extended Middle East and North Africa: summary recommendations for the prevention
      of human papillomavirus infections and related cancers including cervical cancer.

PMID- 24331824
TI  - The path to eliminate cervical cancer in the world and the challenges of
      professional education.

PMID- 24331825
TI  - Extended Middle East and North Africa: cervical cancer and human papillomavirus:
      can we make the case for prevention in this "relatively" low prevalence region?

PMID- 24331826
TI  - Placental pathology and neurological morbidity in preterm infants during the
      first two weeks after birth.
AB  - BACKGROUND: The placenta plays a crucial role during pregnancy and dysfunction
      causes long-term neurological problems. Identifying placenta-related risks for
      neurological problems shortly after birth may provide clues for early
      interventions aiming to improve neurological outcome. OBJECTIVE: To determine the
      association between placental pathology and neurological morbidity in preterm
      infants during the first two weeks after birth. STUDY DESIGN: Placentas of 52
      singleton, preterm infants (GA: 25-31weeks, BW: 560-2250 grammes) were examined
      for histopathology. The infants' neurological condition shortly after birth was
      determined by assessing the quality of their general movements (GMs): normal,
      abnormal, or hypokinetic, on days 5, 8, and 15. A motor optimality score (MOS)
      was also assigned. RESULTS: Examination of the placentas revealed maternal
      vascular underperfusion (n=29), ascending intrauterine infection (AIUI) (n=19),
      villitis of unknown aetiology (n=6), chronic deciduitis (n=11), foetal thrombotic
      vasculopathy (FTV) (n=9), and elevated nucleated red blood cells (NRBCs) as a
      marker for foetal hypoxia (n=7). None of the placental lesions were significantly
      associated with the quality of GMs or MOS. CONCLUSIONS: This study indicated that
      placental lesions were not associated with infants' neurological condition as
      measured by the quality of their general movements during the first two weeks
      after birth.

PMID- 24331827
TI  - Intubation in the delivery room: experience with nasal midazolam.
AB  - BACKGROUND: Neonates are often intubated in the delivery room (DR) without
      anesthesia because vascular access is impossible. AIMS: To assess neonatal
      comfort and adverse events after use of nasal midazolam (nMDZ) for intubation in
      the DR. STUDY DESIGN: Prospective data collection over 6months on the intubation
      of neonates with respiratory distress requiring tracheal instillation of
      surfactant. SUBJECTS: Twenty-seven neonates with median (Q25-75) gestational age
      and birthweight of, respectively, 29 (27-33)weeks and 1270 (817-1942)g received a
      0.1mg/kg dose of nMDZ, and intubation was performed at the onset of tonus
      resolution or apnea. OUTCOME MEASURES: Comfort was assessed with a scale of
      hetero-pain assessment and electrical skin conductance monitoring. Continuous
      pulse oximetry was recorded in the first postnatal hour, with oscillometric blood
      pressure measurement every 10min. RESULTS: Seventy percent of the patients
      required a single dose, with intubation performed 4.8 (3-9)min after
      administration. Combined electro-clinical assessment found adequate comfort
      during the procedure in 68% of neonates. Mean blood pressure decreased from 39
      (34-44)mmHg before to 31 (25-33)mmHg 1h following nMDZ (p=0.011). CONCLUSION:
      nMDZ provided rapid and effective sedation to intubate neonates in the DR but
      potentially exposed them to hypotension, thus requiring close hemodynamic
      monitoring.

PMID- 24331829
TI  - A longitudinal study of body dissatisfaction and pubertal timing in an ethnically
      diverse adolescent sample.
AB  - In a 7-year study, adolescents' body dissatisfaction (N=1370) was examined across
      four high school years as a function of pubertal development (perceived timing
      relative to peers and self-reported physical changes measured during Grades 6-10)
      in the context of the high school transition. Boys and girls who, during early
      high school, perceived themselves to be late relative to peers were at risk for
      body dissatisfaction across the high school years. Boys who were late in pubertal
      development reported more body dissatisfaction in early high school than on-time
      boys, but then decreased over time. African-American girls reported less body
      dissatisfaction across the high school years relative to other girls. Asian girls
      reported more dissatisfaction in early high school than African-American, Latina,
      and Multiethnic girls, and increased over time. Results highlight the importance
      of considering late development within context as a risk factor in body
      dissatisfaction research. 

PMID- 24331830
TI  - Appearance investment mediates the association between fear of negative
      evaluation and dietary restraint.
AB  - This study investigated whether appearance investment explains the association
      between fear of negative evaluation and dietary restraint. Data were collected
      from 305 undergraduate female participants in an online survey. Mediation
      analyses were conducted using Preacher and Hayes (2008) Indirect Mediation macro.
      Results showed that both components of appearance investment that is, holding
      appearance as central to self-definition and the tendency to engage in appearance
      management behaviours, mediate the association between fear of negative
      evaluation and dietary restraint. The Baron and Kenny (1986) method further
      showed that holding appearance as central to self-definition fully mediates this
      association but that engagement in appearance management behaviours only
      partially mediates it. These results suggest that appearance investment could
      prompt women to diet to try to lose weight to fend off feared negative evaluation
      from others. 

PMID- 24331828
TI  - Prenatal maternal depression is associated with low birth weight through shorter
      gestational age in term infants in Korea.
AB  - BACKGROUND: Maternal prenatal depression is associated with lower offspring birth
      weight, yet the impact of gestational age on this association remains
      inadequately understood. AIMS: We aimed to investigate the effect of prenatal
      depression on low birth weight, gestational age, and weight for gestational age
      at term. STUDY DESIGN: Prospective cohort study. SUBJECT: Data were collected
      from 691 women in their third trimester of pregnancy who went on to give birth to
      a singleton at term without perinatal complications. One hundred and fifty-two
      women had a Center for Epidemiologic Studies Depression Scale-10 score >=10 and
      were classed as prenatally depressed. OUTCOME MEASURES: Low birth weight
      (<2500g), gestational age at birth, and birth weight percentile for gestational
      age. RESULTS: Offspring of prenatally depressed women were more likely to be low
      birth weight (Odds ratio [OR] 2.94, 95% confidence interval [CI] 1.14-7.58) than
      offspring of prenatally non-depressed women, but the association was attenuated
      (OR 1.66, 95% CI 0.55-5.02) when adjusted for gestational age. Offspring of
      prenatally depressed women had lower gestational age in weeks (OR for one week
      increase in gestational age: 0.66, 95% CI 0.47-0.93) than offspring of prenatally
      non-depressed women. There was no association between prenatal depression and
      birth weight percentile for gestational age. CONCLUSIONS: Prenatal depression was
      not associated with low birth weight at term, but was associated with gestational
      age, suggesting that association between maternal depression and birth weight may
      be a reflection of the impact of depression on offspring gestational age.

PMID- 24331831
TI  - The disturbance of TH17-Treg cell balance in adenomyosis.
AB  - OBJECTIVE: To investigate the balance between regulatory T cells (Treg) and T
      helper 17 cells (T(H)17) in peripheral blood and uteri of women with adenomyosis
      (AM), and to evaluate their potential correlation with dysmenorrhea and CA-125
      levels. DESIGN: Laboratory study using human peripheral blood and tissues.
      SETTING: Academic hospital. PATIENT(S): Forty-five patients with AM (study group)
      and 25 women without AM (control group). INTERVENTION(S): The peripheral blood
      and tissues harvested from all groups were subjected to flow cytometry, ELISA,
      quantitative real-time polymerase chain reaction, and immunohistochemistry. The
      severity of dysmenorrhea was distinguished by visual analog scale (VAS). MAIN
      OUTCOME MEASURE(S): T(H)17 and Treg cell frequency, mRNA and protein levels of
      transcription factors and cytokines in all groups, and their correlation between
      the T(H)17-Treg ratio and dysmenorrhea severity or CA-125 level. RESULT(S): The
      disturbance of T(H)17-Treg balance was demonstrated in peripheral circulation and
      uteri of patients with both diffuse and focal AM, and it correlated positively
      with dysmenorrhea severity and CA-125. CONCLUSION(S): The findings suggest that
      T(H)17-Treg imbalance may play a crucial role in the immunopathogenesis of AM,
      and may be thus a potential target of AM therapy. CLINICAL TRIAL REGISTRATION
      NUMBER: ChiCTR-CCC-13003500.

PMID- 24331832
TI  - Meiotic spindle normality predicts live birth in patients with recurrent in vitro
      fertilization failure.
AB  - OBJECTIVE: To investigate the impact of meiotic spindle normality on live birth
      rates in women with recurrent IVF failure. DESIGN: A retrospective comparative
      study. SETTING: A large private sector IVF service in Sydney, Australia.
      PATIENT(S): Five hundred five intracytoplasmic sperm injection (ICSI)/ET cycles
      of patients who fulfilled the criteria for recurrent IVF failure, three or more
      previous fresh or frozen ETs with no ongoing pregnancy. INTERVENTION(S):
      Polarized light microscopy was used at the time of ICSI. MAIN OUTCOME MEASURE(S):
      Clinical pregnancy rates (PR) and live birth rates (LBR) were compared depending
      on the morphology of the meiotic spindle of the oocyte(s) from which the
      embryo(s) were transferred. RESULT(S): Women receiving embryos where at least one
      was derived from a normally spindled oocyte had significantly increased clinical
      PR and LBR when compared with those who had only embryos derived from abnormally
      spindled oocytes (clinical PR: 31% vs. 7%; odds ratio [OR], 6.45; 95% confidence
      interval [CI] 3.65-11.40) and (LBR: 24% vs. 4%; OR, 7.24; 95% CI 3.62-14.49).
      Comparison between the abnormal spindle groups showed significantly higher
      clinical PR and LBR from the group of patients receiving embryos where at least
      one was derived from an oocyte with no visible spindle compared with the group
      receiving embryos from dysmorphic spindles only (clinical PR: 9% vs. 6%; OR,
      0.58; 95% CI 0.22-1.57 and LBR: 8% vs. 1%; OR, 0.16; 95% CI 0.03-0.77).
      CONCLUSION(S): Normally spindled oocytes, as determined by polarized light
      microscopy, are associated with significantly higher clinical PRs in patients
      with recurrent IVF failure.

PMID- 24331833
TI  - Validation of a new menstrual pictogram (superabsorbent polymer-c version) for
      use with ultraslim towels that contain superabsorbent polymers.
AB  - OBJECTIVE: To validate the menstrual pictogram (superabsorbent polymer-c version)
      for Always Ultra-slim feminine towels containing superabsorbent polymers. DESIGN:
      Prospective, multicenter, evaluator-blinded study. SETTING: Three gynecology
      research clinics in the United Kingdom. PATIENT(S): Women with self-perceived
      light, normal, or heavy menstrual periods who had not previously used a graphical
      method to assess their menstrual loss. INTERVENTION(S): One hundred twenty-two
      women were asked to complete the menstrual pictogram throughout two menstrual
      periods and collect their feminine towels for measurements of menstrual blood
      loss (MBL) by the alkaline hematin method and total menstrual fluid loss (MFL) by
      fluid weight. MAIN OUTCOME MEASURE(S): Agreement of menstrual pictogram MBL and
      MFL scores with alkaline hematin and towel weight, respectively. The percentage
      blood fraction was determined at various volumes of menstrual discharge.
      RESULT(S): Alkaline hematin and fluid weight were highly correlated (r = .97).
      However, the percentage blood fraction progressively increased with total MFL and
      MBL score. After correction for this incremental rise in blood fraction, the
      menstrual pictogram gave a sensitivity of 82% and a specificity of 92% for a
      diagnosis of heavy menstrual bleeding. CONCLUSION(S): The menstrual pictogram
      (superabsorbent polymer-c version) provides a simple means of measuring MBL in
      the clinical setting.

PMID- 24331834
TI  - Thawed human sperm quality is influenced by the volume of the cryopreserved
      specimen.
AB  - OBJECTIVE: To test the effect of sperm specimen volume in the freezing-thawing
      process on specimen quality. DESIGN: Experimental prospective study. SETTING:
      Tertiary academic medical center. PATIENT(S): Fifty high-quality sperm donors
      donated ~3 times each. Sperm samples were split into two aliquots and frozen in
      volumes of 0.25 mL and 0.5 mL. INTERVENTION(S): Semen analyses. MAIN OUTCOME
      MEASURE(S): Eight sperm quality parameters of thawed specimens. RESULT(S): Thawed
      0.5-mL specimens had a higher percentage of motility and viability, progressive
      motility concentration, percentage of cells with high mitochondrial membrane
      potential, and intact chromatin compared with 0.25-mL specimens. Although there
      were fewer cells with intact acrosomes in the 0.5-mL thawed samples, they had a
      similar ability to respond to ionophore by acrosome reaction as the 0.25-mL
      specimens. Both groups had similar percentages of cells with oxidative stress and
      numbers of cells that bound to the zona pellucida. The remaining air volume in
      the straw and freezing medium composition had a minimal effect on tested
      parameters. CONCLUSION(S): Better quality thawed human sperm was achieved after
      cryopreservation of high volumes compared with low volumes of specimens. Air
      volume in the straw had no influence on specimen quality.

PMID- 24331835
TI  - Change in oocyte yield in repeated in vitro fertilization cycles: effect of
      ovarian reserve.
AB  - OBJECTIVE: To examine factors that affect variability in oocyte yield between
      consecutive IVF cycles. DESIGN: Retrospective cohort study. SETTING: University
      based fertility clinic. PATIENT(S): A total of 292 women starting two IVF cycles
      within 12 months from 2005 to 2011. INTERVENTION(S): Variables evaluated included
      female age, body mass index, parity, infertility diagnosis, antral follicle count
      (AFC), ovarian stimulation protocol, change in stimulation protocol, total dose
      of gonadotropin used and change in dose between cycles. Possible associations
      were tested using a log linear regression model. MAIN OUTCOME MEASURE(S): Change
      in total and mature oocyte yield between cycles and factors that predict this
      change. RESULT(S): In cycle 1, total and mature oocyte yield were positively
      associated with increased AFC and negatively associated with total gonadotropin
      dose. In cycle 2, a significant increase was seen in both total and mature
      oocytes. There were no significant independent variables that predicted this
      change in oocyte yield. When stratified into groups based on ovarian reserve,
      change in oocyte yield between cycles was significant only in patients with
      normal ovarian reserve (AFC >10). In this group, the only independent variable
      associated with an increased oocyte yield was an increase in the total
      gonadotropin dose. CONCLUSION(S): An increase in oocyte yield between cycles was
      found in women with normal ovarian reserve and was associated with an increased
      total gonadotropin dose in the second cycle.

PMID- 24331836
TI  - Pregnancies of unknown location after in vitro fertilization: minimally invasive
      management with Karman cannula aspiration.
AB  - OBJECTIVE: To describe a standardized protocol for the assessment of asymptomatic
      patients with pregnancies of unknown location (PUL) after IVF. DESIGN:
      Retrospective cohort study. SETTING: University-based infertility clinic.
      PATIENT(S): Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI)
      cycles between 2005 and 2011. INTERVENTION(S): Endometrial sampling using Karman
      suction cannula in patients with PUL and abnormal beta-hCG trend (increase <53%
      or decrease <15% in 2 days) and a pelvic ultrasound unremarkable for an
      intrauterine pregnancy (IUP) or an ectopic pregnancy (EP). MAIN OUTCOME
      MEASURE(S): Proportion of patients spared methotrexate (MTX) administration.
      RESULT(S): Endometrial sampling was performed in 45 patients. Of these, 31
      (68.9%) were diagnosed with failed IUP by either a sampling after the beta-hCG
      decline (>=15%) and/or the presence of villi on final pathology. No further
      intervention was required. Fourteen patients (31.1%) were diagnosed with presumed
      EP by persistent beta-hCG level after negative pathology. Ten of these patients
      (71%) were successfully treated with a single dose of MTX; three required an
      additional dose, and one required laparoscopy for a ruptured EP. CONCLUSION(S):
      In asymptomatic patients with PUL and abnormal beta-hCG trends after IVF, the
      utility of Karman aspiration to confirm an IUP may obviate treatment with MTX in
      more than two-thirds of patients.

PMID- 24331837
TI  - [Decision making in the patient of very advanced age with heart disease. Beyond
      cardiology risk scores].

PMID- 24331838
TI  - [Guidelines on the management of implantable cardioverter defibrillators at the
      end of life].
AB  - This article is a joint document of the Spanish Society of Geriatrics and
      Gerontology, the Spanish Society of Palliative Care and the Section of Geriatric
      Cardiology of the Spanish Society of Cardiology. Its aim is to address the huge
      gap that exists in Spain with regard to the management of implantable
      cardioverter defibrillators (ICDs) in the final stages of life. It is
      increasingly common to find patients carrying these devices that are in the
      terminal stage of an advanced disease. This occurs in patients with advanced
      heart disease and subsequent heart failure refractory to treatment but also in a
      patient with an ICD who develops cancer disease, organ failure or other
      neurodegenerative diseases with poor short-term prognosis. The vast majority of
      these patients are over 65, so the paper focuses particularly on the elderly who
      are in this situation, but the decision-making process is similar in younger
      patients with ICDs who are in the final phase of their life. 

PMID- 24331839
TI  - Immunohistochemical study of 36 cases of pulmonary sarcomatoid carcinoma-
      sensitivity of TTF-1 is superior to napsin.
AB  - Immunohistochemistry is often used to distinguish pulmonary sarcomatoid carcinoma
      from morphologic mimics. Napsin-A is a pulmonary adenocarcinoma marker, but
      literature on expression in sarcomatoid carcinoma is limited. Thirty-six cases of
      sarcomatoid carcinoma were stained for napsin, TTF-1, Oscar, CAM5.2, AE1/AE3,
      desmin, SMA, S-100, CK5/6, calretinin, D2-40, and WT1. Patients were 24 men and
      12 women (mean, 70 years; range, 46-93). There were 27 pleomorphic carcinomas, 5
      spindle cell carcinomas, 3 carcinosarcomas, and 1 giant cell carcinoma. Cases
      were positive for at least 1 keratin: AE1/3 was positive in all 36 cases; Oscar,
      in 34 cases (94%); and CAM5.2, in 32 cases (89%, weaker/more focal). Napsin was
      positive in 14 cases (39%): 8 diffuse, 3 focal, and 3 rare cells. TTF-1 was
      positive in 22 cases (61%): 15 diffuse, 3 focal, and 4 rare cells. No cases were
      napsin positive and negative for TTF-1. Variable staining for mesothelial markers
      was observed, including positivity for calretinin (12 cases, 33%), WT1 (6 cases,
      17%), D2-40 (5 cases, 14%), and CK5/6 (9 cases, 25%). Mesenchymal markers were
      also sometimes positive (usually focal), including S-100 (4 cases, 11%), desmin
      (4 cases, 11%), and SMA (7 cases, 19%, 1 diffuse). In conclusion, TTF-1 is more
      sensitive than napsin for detection of sarcomatoid carcinoma, and no cases were
      positive for napsin but negative for TTF-1. CAM5.2 is less sensitive than AE1/AE3
      and Oscar. Use of a thoughtful immunohistochemical panel is important in the
      evaluation of sarcomatoid carcinoma because mesothelial and mesenchymal markers
      can be expressed. 

PMID- 24331840
TI  - Crohn enteritis-associated small bowel adenocarcinomas exhibit gastric
      differentiation.
AB  - Primary small bowel adenocarcinoma is rare. Although generally similar to colonic
      adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic
      features, particularly those arising in association with Crohn disease. In this
      study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated
      small bowel adenocarcinomas were examined for histology and immunohistochemical
      profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2,
      and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis
      associated small bowel adenocarcinomas frequently resemble gastric tubular
      adenocarcinoma histologically. In addition, when compared to sporadic small bowel
      adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency
      (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated
      small bowel adenocarcinomas (91%) were positive for at least one gastric-type
      marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn
      enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression
      of CK20 was less frequent (64% vs. 100%). There was no difference between
      sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression
      of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that
      there is a difference in the morphologic and immunohistochemical characteristics
      of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma,
      particularly in their expression of gastric-type mucin. The findings also suggest
      that gastric differentiation in Crohn enteritis-associated small bowel
      adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn
      disease. 

PMID- 24331841
TI  - Prognostic implications of tumor-infiltrating FoxP3+ regulatory T cells and CD8+
      cytotoxic T cells in microsatellite-unstable gastric cancers.
AB  - Microsatellite instability (MSI)-high gastric cancers (GC) have better prognosis
      and higher levels of tumor-infiltrating lymphocytes (TIL) compared with MSI-low
      or MSI-stable GCs. TILs are part of the adaptive immune response against tumor
      growth and are associated with improved prognosis in GCs. The aim of this study
      was to investigate the prognostic significance of CD8+ and FoxP3+ TILs in MSI
      high GCs and their relationships with various clinicopathologic characteristics.
      Intratumoral intraepithelial CD8+ and FoxP3+ TILs were assessed in 99 cases of
      MSI-high GCs using a computerized image analysis system. TILs were grouped into
      low- and high-density groups and were analyzed for their relationships with
      clinicopathologic parameters. A low density was closely associated with a higher
      TNM stage (P = .040) and invasion depth (P = .044) and more frequent lymphatic
      and vascular invasion (P = .033 and .015, respectively). GCs with high-density
      CD8+ or FoxP3+ TILs showed significantly higher overall survival rates than those
      of GCs with low-density CD8+ or FoxP3+ TILs (P = .017 and .013, respectively,
      Kaplan-Meier test). In multivariate survival analysis, a high density of FoxP3+
      TILs was significantly associated with improved overall survival (P = .027;
      hazard ratio, 0.269), and the combinatorial status of CD8+ and FoxP3+ TIL density
      was an independent prognostic factor (P = .003). Our results demonstrate that
      higher densities of both intratumoral CD8+ and FoxP3+ TILs are associated with
      good prognosis, suggesting a synergistic activity of these 2 subsets that can be
      used as an independent prognostic factor in MSI-high GCs. 

PMID- 24331842
TI  - The effect of milrinone on induced hypotension in elderly patients during spinal
      surgery: a randomized controlled trial.
AB  - BACKGROUND CONTEXT: Induced hypotension is widely used intraoperatively to reduce
      blood loss and to improve the surgical field during spinal surgery. PURPOSE: To
      determine the effect of milrinone on induced hypotension during spinal surgery in
      elderly patients. STUDY DESIGN/SETTING: Prospective randomized clinical trial.
      PATIENT SAMPLE: Forty patients, 60 to 70 years old, ASA I-II, who underwent
      elective lumbar fusion surgery. OUTCOME MEASURES: Intraoperative hemodynamics,
      blood loss, hourly urine output, and grade of surgical field. METHODS: All
      patients were randomized to group M or N. The study drug was infused after
      perivertebral muscle retraction until complete interbody fusion. In group M, 50
      MUg/kg/min of milrinone was infused over 10 minutes as a loading dose followed by
      0.6 MUg/kg/min of milrinone as a continuous dose. In group N, an identical volume
      of normal saline was infused in the same fashion. This study was not funded by
      commercial or other sponsorship and the authors confirm no conflicts of interest,
      financial or otherwise. RESULTS: During infusion of the study drug, the systolic
      and mean blood pressures were maintained within adequate limits of induced
      hypotension in group M. Intraoperative blood loss was 445.0+/-226.5 mL in group M
      and 765.0+/-339.2 mL in group N (p=.001). Hourly urine output was 1.4+/-0.6 mL in
      group M and 0.8+/-0.2 mL in group N (p<.001). The grade of the surgical field was
      better in group M than in group N (p=.004). CONCLUSIONS: We conclude that
      milrinone is useful for induced hypotension in elderly patients during spinal
      surgery.

PMID- 24331843
TI  - Spinal brucellosis in South of Tunisia: review of 32 cases.
AB  - BACKGROUND CONTEXT: Brucellosis remains an important economic and public health
      problem in some parts of the world. The spine is the most common site of
      musculoskeletal involvement of brucellosis. PURPOSE: Assess the clinical,
      laboratory, radiological findings, and outcomes of vertebral involvement in
      brucellosis. STUDY DESIGN: A retrospective study. PATIENT SAMPLE: Thirty-two
      patients with spinal brucellosis during a period of 21 years (1990-2010) were
      included. OUTCOME MEASURES: Clinical and radiological improvement. METHODS:
      Diagnosis made on clinical presentation, laboratory findings, radiographic
      evidence, and the Brucellar etiology was considered when seroagglutination tests
      were positive at a titer of 1/160 or higher, and/or Brucella spp were isolated in
      the blood or sample cultures. RESULTS: The mean age of patients was 51+/-15.85
      years (23 males, 9 females; age range, 19-74 years). The median diagnostic delay
      was 3 months. Back or neck pain (100% of patients), fever (78%), and sweats
      (68.6%) were the most common symptoms. Cultures of blood specimens from five
      patients (15.6%) were positive for Brucella melitensis. Four patients (12.5%) had
      motor weakness or paralysis. Magnetic resonance imaging was performed in 24 (75%)
      cases. Paravertebral masses, epidural masses, and psoas abscesses were detected
      in 65.6%, 59.4%, and 28.1% of patients, respectively. The lumbar vertebra was the
      most frequently involved region with the rate of 68.7%, followed by thoracal
      (18.7%), cervical (6.3%), lumbosacral (6.3%), and thoracolumbar (3.1%) segments.
      The duration of antimicrobial therapy of brucellosis (median, 6 months; range, 3
      13 months) varied according to clinical response and the presence of epidural and
      paravertebral masses. There were no deaths or severe sequelae in this study.
      CONCLUSIONS: Brucellar spondylitis should be considered in patients with back
      pain and fever in endemic areas. A high index of suspicion and clinical,
      laboratory, and radiological examinations help to confirm the diagnosis of
      vertebral involvement.

PMID- 24331844
TI  - Presentation of cauda equina syndrome due to an intradural extramedullary
      abscess: a case report.
AB  - BACKGROUND CONTEXT: Cauda equina syndrome is caused by compression or injury to
      the nerve roots distal to the level of the spinal cord. This syndrome presents as
      low back pain, motor and sensory deficits in the lower extremities, and bladder
      as well as bowel dysfunction. Although various etiologies of cauda equina
      syndrome have been reported, a less common cause is infection. PURPOSE: To report
      a case of cauda equina syndrome caused by infection of an intradural
      extramedullary abscess with Staphylococcus aureus. STUDY DESIGN/SETTING: Case
      report and review of the literature. METHODS: The literature regarding the
      infectious causes of cauda equina syndrome was reviewed and a case of cauda
      equina syndrome caused by infection of an intradural extramedullary abscess with
      Staphylococcus aureus was reported. RESULTS: A 37-year-old woman, with history of
      intravenous drug abuse, hepatitis C, and hepatitis B, presented with low back
      pain lasting 2 months, lower extremity pain, left greater than right with
      increasing weakness and difficulty ambulating, and urinary and fecal
      incontinence. Her presentation was consistent with cauda equina syndrome. The
      patient underwent a T12-L2 laminectomy, and intradural exploration revealed an
      abscess. Methicillin-resistant Staphylococcus aureus was found on wound culture.
      CONCLUSIONS: Cauda equina syndrome, presenting as a result of spinal infection,
      such as the case reported here, is extremely rare but clinically important.
      Surgical intervention is generally the recommended therapeutic modality.

PMID- 24331845
TI  - Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: lesion
      detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal
      organ tissues.
AB  - PURPOSE: To compare the performance of PET/MRI imaging using MR attenuation
      correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with
      that of PET/CT using CT-based attenuation correction and to compare the
      quantification accuracy in lesions and in normal organ tissues. METHODS: A total
      of 36 patients underwent a whole-body PET/CT scan 1h after injection and an
      average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and
      PET/CT were compared visually by rating anatomic allocation and image contrast.
      Regional tracer uptake in lesions was quantified using volumes of interest, and
      maximal and mean standardized uptake values (SUVmax and SUVmean, respectively)
      were calculated. Metabolic tumor volume (MTV) of each lesion was computed on
      PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax
      and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle.
      RESULTS: Overall 74 FDG positive lesions were visualized by both PET/CT and
      PET/MRI. No significant differences in anatomic allocation scores were found
      between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was
      significantly higher. Both SUVmax and SUVmean of lesions were significantly
      higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and
      PET/CT data (rho=0.71-0.88). MTVs of all lesions were 4% lower on PET/MRI than on
      PET/CT, but no statistically significant difference was observed, and an
      excellent correlation between measurements of MTV with PET/MRI and PET/CT was
      found (rho=0.95-0.97; p<0.0001). Both SUVmax and SUVmean were significantly lower
      by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference
      was observed for spleen, while either SUVmax and SUVmean of myocardium were
      significantly higher by PET/MRI. High correlations were found between PET/MRI and
      PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (rho=0.91;
      p<0.0001), while moderate correlations were found for the other normal organ
      tissues (rho=0.36-0.61; p<0.05). CONCLUSIONS: PET/MRI showed equivalent
      performance in terms of qualitative lesion detection to PET/CT. Despite
      significant differences in tracer uptake quantification, due to either
      methodological and biological factors, PET/MRI and PET/CT measurements in lesions
      and normal organ tissues correlated well. This study demonstrates that integrated
      whole-body PET/MRI is feasible in a clinical setting with high quality and in a
      short examination time.

PMID- 24331846
TI  - Evaluating data capture methods for the establishment of diagnostic reference
      levels in CT scanning.
AB  - OBJECTIVE: Concerns about the radiation dose associated with CT scanning have led
      to a call for establishment of diagnostic reference levels. Self-complete surveys
      have been used extensively to gather this information, however, departmental
      Radiological Information System's/Picture Archive Communication Systems
      (RIS/PACS) also hold this information. We compared dosimetry derived from survey
      with that using RIS/PACSs. METHODS: Technical data were collected from a large
      metropolitan tertiary hospital in WA using both data collection methods for a
      range of adult CT scanning examinations. Radiation dose was calculated from both
      datasets and the results evaluated for several indexes of inter-rater agreement.
      RESULTS: Radiation dose calculated using self-report survey data differed both
      systematically and proportionally from that calculated using RIS/PACS data.
      Differences were not consistent across CT examination type and thus not amenable
      to simple correction. The disparity was greater and more variable for organ dose
      than effective dose due to reliance of survey data on "generic" anatomical start
      and stop limits compared with actual data available on RIS/PACS. CONCLUSIONS: The
      bias observed in our study indicates that care should be taken when interpreting
      the results of studies measuring radiation dose using self-complete surveys. The
      availability of electronic databases that include information required for the
      evaluation and monitoring of CT radiation dose provides the opportunity to
      capture better quality data in a cost-effective manner. We recommend that
      national and local databases are established that routinely capture these data so
      as to facilitate the development and monitoring of radiation dose associated with
      CT scanning.

PMID- 24331847
TI  - Clinical protocols for 31P MRS of the brain and their use in evaluating optic
      pathway gliomas in children.
AB  - INTRODUCTION: In vivo (31)P Magnetic Resonance Spectroscopy (MRS) measures
      phosphorus-containing metabolites that play an essential role in many disease
      processes. An advantage over (1)H MRS is that total choline can be separated into
      phosphocholine and glycerophosphocholine which have opposite associations with
      tumour grade. We demonstrate (31)P MRS can provide robust metabolic information
      on an acceptable timescale to yield information of clinical importance. METHODS:
      All MRI examinations were carried out on a 3T whole body scanner with all (31)P
      MRS scans conducted using a dual-tuned (1)H/(31)P head coil. Once optimised on
      phantoms, the protocol was tested in six healthy volunteers (four male and two
      female, mean age: 25+/-2.7). (31)P MRS was then implemented on three children
      with optic pathway gliomas. RESULTS: (31)P MRS on volunteers showed that a number
      of metabolite ratios varied significantly (p<0.05 ANOVA) across different
      structures of the brain, whereas PC/GPC did not. Standard imaging showed the
      optic pathway gliomas were enhancing on T1-weighted imaging after contrast
      injection and have high tCho on (1)H MRS, both of which are associated with high
      grade lesions. (31)P MRS showed the phosphocholine/glycerophosphocholine ratio to
      be low (<0.6) which suggests low grade tumours in keeping with their clinical
      behaviour and the histology of most biopsied optic pathway gliomas. CONCLUSION:
      (31)P MRS can be implemented in the brain as part of a clinical protocol to
      provide robust measurement of important metabolites, in particular providing a
      greater understanding of cases where tCho is raised on (1)H MRS.

PMID- 24331848
TI  - Practice-based clinical evaluation of ceramic single crowns after at least five
      years.
AB  - STATEMENT OF PROBLEM: Long-term practice-based clinical evaluations of various
      contemporary ceramic crown restorations from multiple practitioners are limited.
      PURPOSE: The aims of this study were to evaluate the clinical performance of
      ceramic single crowns and to identify factors that influence their clinical
      performance. MATERIAL AND METHODS: Ceramic single crowns that had been placed at
      the Mayo Clinic and in function since 2005 were identified and included in the
      study. The restorations were examined clinically, radiographically, and with
      photographs. Modified United States Public Health Services criteria were used for
      the clinical evaluation. The ceramic systems evaluated were bilayer and
      monolayer. RESULTS: Fifty-nine patients (41 women, 18 men) with 226 single teeth
      and implants restored with single ceramic crowns were identified. The mean
      duration from insertion date to study examination date was 6.1 years. Thirteen
      restorations (6%) were replaced at a mean 3.3 years after insertion date (range,
      0.1-6.1 years). Estimated replacement-free survival rates (95% confidence
      interval [CI]; number of teeth/implants still at risk) at 5 years after insertion
      date were 95.1% (95% CI, 92.2-98.1; 153) and at 10 years were 92.8% (95% CI, 89.1
      96.8; 8). The most common reason for replacement was fracture to the core of
      posterior layered ceramic crowns. The most commonly used luting agent was resin
      modified ionomer cement. Most restorations exhibited clinically acceptable
      marginal integrity, shade, no caries recurrence, and no periapical pathology.
      CONCLUSIONS: The clinical performance of ceramic single crowns at 5 and 10 years
      supports their application in all areas of the mouth. With the majority of
      fractures to the core occurring early in the lifetime of layered ceramic
      posterior crowns, consideration of other monolithic ceramic systems for posterior
      crowns is advised.

PMID- 24331849
TI  - Effect of adaptation time on the occlusal force at denture dislodgement with or
      without denture adhesive.
AB  - STATEMENT OF PROBLEM: The effect of denture adhesives on the occlusal forces at
      the dislodgement (OFD) of new complete dentures during the adaptation period has
      not been previously studied. PURPOSE: The purpose of this study was to
      investigate the OFD of dentures after their insertion and 3 months later, with or
      without denture adhesives. MATERIAL AND METHODS: Thirteen volunteers with
      edentulism were enrolled in the study. Each participant had new complete
      maxillary and mandibular dentures. The occlusal forces (N) at denture
      dislodgement were assessed with or without 2 adhesives by using an electronic
      gnathodynamometer in the incisal and premolar regions on the existing denture,
      the new denture immediately after fitting, 45 days later, and 90 days later. The
      statistical analysis included the Wilcoxon and Kruskal-Wallis tests, repeated
      measures ANOVA, and the Pearson coefficient at alpha=.05. RESULTS: Repeated
      measures ANOVA for new dentures showed that the OFD in the incisal or premolar
      region were significantly different between adaptation periods (P<.05) but not
      between adhesives. OFDs of dentures with and without adhesives correlated highly
      at all adaptation periods (0.912 to 0.995). CONCLUSIONS: The adaptation period
      does affect the OFD of new dentures, but the 2 adhesives were found to have the
      same effect on the OFD.

PMID- 24331850
TI  - Change in masticatory ability with the implant restoration of second molars.
AB  - STATEMENT OF PROBLEM: Controversy exists as to whether missing second molars
      should be replaced to restore masticatory ability. PURPOSE: The purpose of this
      study was to analyze the alteration in masticatory ability associated with the
      implant restoration of the second molar; the subjective effect of implant
      treatment on the participant was also assessed. MATERIAL AND METHODS: Twenty-one
      individuals (13 men and 8 women) participated. Masticatory ability was recorded
      before the cementation of implant-supported single crowns, immediately after
      cementation, and 1 month after cementation. The occlusal load (Pa), the load
      bearing contact area (mm(2)), and the maximum occlusal force (N) were calculated.
      A subjective evaluation of masticatory ability was conducted before treatment and
      1 month after treatment through the use of a questionnaire to evaluate chewing
      difficulties and global satisfaction with treatment. The Wilcoxon signed rank
      test was used to analyze the difference in scores. RESULTS: The load-bearing
      contact area, maximum occlusal force, and participant satisfaction were found to
      increase significantly 1 month after the cementation of implant-supported single
      crowns. The restoration of the second molar with an implant increased both
      objective masticatory ability and subjective satisfaction 1 month after
      cementation of the implant-supported single crowns. CONCLUSIONS: Patients
      presenting with a missing second molar may benefit from replacement with implant
      supported crowns. Longer study periods and larger sample populations are needed
      to obtain more definitive results.

PMID- 24331851
TI  - Influence of changes in the oral cavity on the performance of recorder players: a
      pilot study.
AB  - STATEMENT OF PROBLEM: Wind instrument players may dread dental treatment because
      changes in the oral cavity can affect their performance. However, few studies
      have investigated the influence of such changes, particularly prosthesis-induced
      morphologic changes, on the performance of wind instrument players. PURPOSE: The
      purpose of this study was to determine the effects of prosthesis-induced
      morphologic changes in the oral cavity on the performance of wind instrument
      players. MATERIAL AND METHODS: Seven women were asked to play a recorder with and
      without an experimental palatal appliance. Their performances were analyzed by
      psychoacoustic analysis, with loudness as a parameter, and by performable range
      analyses with Voice Range Profile software. The Wilcoxon signed rank test was
      used for the statistical analyses. RESULTS: Differences between moderately loud
      and very soft sounds (P=.043) and between very loud and very soft sounds
      (P=.027), as well as the performable range of frequency and intensity (P=.028),
      all decreased significantly in the presence of the palatal prosthesis.
      CONCLUSIONS: The results of this study suggest that changes in the oral cavity
      caused by the presence of a prosthesis affect the psychoacoustic features and the
      performable range of frequency and intensity during the playing of wind
      instruments.

PMID- 24331852
TI  - Dental caries: an updated medical model of risk assessment.
AB  - Dental caries is a transmissible, complex biofilm disease that creates prolonged
      periods of low pH in the mouth, resulting in a net mineral loss from the teeth.
      Historically, the disease model for dental caries consisted of mutans
      streptococci and Lactobacillus species, and the dental profession focused on
      restoring the lesions/damage from the disease by using a surgical model. The
      current recommendation is to implement a risk-assessment-based medical model
      called CAMBRA (caries management by risk assessment) to diagnose and treat dental
      caries. Unfortunately, many of the suggestions of CAMBRA have been overly
      complicated and confusing for clinicians. The risk of caries, however, is usually
      related to just a few common factors, and these factors result in common patterns
      of disease. This article examines the biofilm model of dental caries, identifies
      the common disease patterns, and discusses their targeted therapeutic strategies
      to make CAMBRA more easily adaptable for the privately practicing professional. 

PMID- 24331853
TI  - Determination of dead-layer variation in HPGe detectors.
AB  - The dead-layer uniformity of the top surface of two high purity germanium
      detectors has been studied using a novel automated scanning set-up that allows a
      fine-grained topography of a detector's top and lateral surfaces. Comparisons
      between measurements and Monte Carlo simulations allowed implementation of a dead
      layer variation into the detector model, which reproduces the measurements
      results. The effect of the non-uniform dead-layer on activity determinations
      based on low-energy gamma-rays (i.e. below ~100 keV) has been determined to be of
      the order of 10% or more.

PMID- 24331854
TI  - Gamma-ray spectrometry method used for radioactive waste drums characterization
      for final disposal at National Repository for Low and Intermediate Radioactive
      Waste--Baita, Romania.
AB  - The Radioactive Waste Management Department from IFIN-HH, Bucharest, performs the
      conditioning of the institutional radioactive waste in concrete matrix, in 200 l
      drums with concrete shield, for final disposal at DNDR - Baita, Bihor county, in
      an old exhausted uranium mine. This paper presents a gamma-ray spectrometry
      method for the characterization of the radioactive waste drums' radionuclides
      content, for final disposal. In order to study the accuracy of the method, a
      similar concrete matrix with Portland cement in a 200 l drum was used.

PMID- 24331855
TI  - Doublet peak area determination in NaI(Tl) scintillation spectrometry using
      maximum likelihood estimation.
AB  - A method has been studied for the analysis of the pulse-height spectrum of a
      mixed (134)Cs and (137)Cs source obtained with a NaI(Tl) scintillation
      spectrometer. A peak fitting technique using maximum likelihood estimation was
      used with a specially developed deconvolution computer program. The activities
      obtained by this program were compared with the reference value in order to
      validate the analysis algorithm. Peak-area determination for NaI(Tl)
      scintillation spectrometry was successfully carried out even for spectra that
      included peak doublet and were recorded with low statistics. The results obtained
      by the maximum likelihood estimation agreed with each reference value within
      their statistical uncertainties. 

PMID- 24331856
TI  - Response of Ge photon detectors to beta-rays and possible reduction of photopeak
      areas due to beta-gamma coincidence summing effects.
AB  - In the use of photon detectors having sensitivity to beta-rays or internal
      conversion electrons (CEs), beta-gamma and/or X-CE coincidence summing may arise.
      In particular, an n-type germanium detector has a thin dead layer and window,
      causing considerably higher sensitivity to beta-rays and/or CEs especially when
      sources are located at a small source-to-detector distance. In the present
      research, reduction of the photopeak area due to beta-gamma or X-CE coincidence
      summing has been studied for three germanium detectors. 

PMID- 24331857
TI  - Preparation of spiked grass for use as an environmental radioactivity reference
      material.
AB  - Measurement of radionuclides from environmental samples includes a wide variety
      of matrix compositions and densities. To improve the traceability of
      environmental monitoring, LNE-LNHB intends to produce mixed gamma-ray reference
      materials with a known mass activity and a composition as representative as
      possible of real environmental samples. This paper describes the preparation and
      characterization of a low density treated grass matrix spiked with mixed gamma
      emitters. This material was used in a proficiency test exercise whose results are
      presented. 

PMID- 24331858
TI  - Standardization of Sm-153 solution by absolute methods.
AB  - Standardization of (153)Sm by 4pi(LS)-gamma coincidence and anticoincidence
      counting and the CIEMAT/NIST method in three LS-counters is presented. This short
      half-life radionuclide is applied in tumor therapy and bone pain palliation. A
      simplified disintegration scheme of (153)Sm was applied in the calculation of the
      counting efficiency. Standard uncertainties of 0.4% for the (153)Sm measurements
      by the 4pi(LS)-gamma coincidence and anticoincidence techniques and 0.7% by the
      C/N method were evaluated, respectively. An agreement of the standardization
      results by both methods within the respective uncertainties was obtained. The
      half-life of (153)Sm of (1.92895+/-0.00024) days was determined during one month
      of measurements and correction for europium isotope impurities by the C/N method
      in the TriCarb 2910 LS-counter. 

PMID- 24331859
TI  - Recent reproductive coercion and unintended pregnancy among female family
      planning clients.
AB  - OBJECTIVE: Reproductive coercion (RC)--birth control sabotage and coercion by
      male partners to become pregnant and to control the outcome of a pregnancy--has
      been associated with a history of both intimate partner physical and sexual
      violence (IPV) and unintended pregnancy among females utilizing reproductive
      health services. The temporal nature of associations of RC and unintended
      pregnancy (distinct from the impact of IPV), however, has remained less clear.
      STUDY DESIGN: A survey was administered to females aged 16-29 years seeking care
      in 24 rural and urban family planning clinics in Pennsylvania (n=3539). RESULTS:
      Five percent of respondents reported RC in the past 3 months, and 12% reported an
      unintended pregnancy in the past year. Among those who reported recent RC, 21%
      reported past-year unintended pregnancy. Compared to women exposed to neither
      condition, exposure to recent RC increased the odds of past-year unintended
      pregnancy, both in the absence of a history of IPV [adjusted odds ratio (AOR)
      1.79, 1.06-2.03] and in combination with a history of IPV (AOR 2.00, 1.15-3.48);
      history of IPV without recent RC was also associated with unintended pregnancy
      (AOR 1.80, 1.42-2.26). CONCLUSIONS: Findings indicate the temporal proximity of
      the association of RC and unintended pregnancy, with recent RC related to past
      year unintended pregnancy, both independently and in combination with a history
      of IPV. Recent RC is relatively prevalent among young women using family planning
      clinics and is associated with increased risk for past-year unintended pregnancy
      even in the absence of IPV. IMPLICATIONS: Recent RC and a history of IPV are
      prevalent among female family planning clients, particularly younger women, and
      these experiences are each associated with unintended pregnancy. Pregnancy
      prevention counseling should include not only assessment for physical and sexual
      partner violence but also specific inquiry about RC.

PMID- 24331860
TI  - Cervical preparation for second-trimester surgical abortion prior to 20 weeks'
      gestation: SFP Guideline #2013-4.
AB  - For a dilation and evacuation (D&E) procedure, the cervix must be dilated
      sufficiently to allow passage of operative instruments and products of conception
      without injuring the uterus or cervical canal. Preoperative preparation of the
      cervix reduces the risk of cervical laceration and uterine perforation. The
      cervix may be prepared with osmotic dilators, pharmacologic agents or both.
      Dilapan-STM and laminaria are the two osmotic dilators currently available in the
      United States. Laminaria tents, made from dehydrated seaweed, require 12-24 h to
      achieve maximum dilation. Dilapan-STM, made of synthetic hydrogel, achieves
      significant dilation within 4 h and is thus preferable for same-day procedures. A
      single set of one to several dilators is usually adequate for D&E before 20
      weeks' gestation. Misoprostol, a prostaglandin E1 analogue, is sometimes used
      instead of osmotic dilators. It is generally regarded as safe and effective;
      however, misoprostol achieves less dilation than overnight osmotic tents. The
      literature supports same-day cervical preparation with misoprostol or Dilapan-STM
      up to 18 weeks' gestation. As the evidence regarding alternative regimens
      increases, highly experienced D&E providers may consider same-day regimens at
      later gestations utilizing serial doses of misoprostol or a combination of
      osmotic and pharmacologic agents. Misoprostol use as an adjunct to overnight
      osmotic dilation is not significantly beneficial before 19 weeks' gestation.
      Limited data demonstrate the safety of misoprostol before D&E in patients with a
      prior cesarean delivery. Mifepristone, a progesterone receptor antagonist, is
      also effective for cervical preparation prior to D&E, although data to support
      its use are limited. The Society of Family Planning recommends preoperative
      cervical preparation to decrease the risk of complications when performing a D&E.
      Since no single protocol has been found to be superior in all situations,
      clinical judgment is warranted when selecting a method of cervical preparation. 

PMID- 24331861
TI  - Scaphoid interfragmentary motions due to simulated transverse fracture and volar
      wedge osteotomy.
AB  - BACKGROUND: Our goal was to determine 3-dimensional interfragmentary motions due
      to simulated transverse fracture and volar wedge osteotomy of the scaphoid during
      physiologic flexion-extension of a cadaveric wrist model. METHODS: The model
      consisted of a cadaveric wrist (n = 8) from the metacarpals through the distal
      radius and ulna with load applied through the major flexor-extensor tendons.
      Flexibility tests in flexion-extension were performed in the following 3 test
      conditions: intact and following transverse fracture and wedge osteotomy of the
      scaphoid. Scaphoid interfragmentary motions were measured using optoelectronic
      motion tracking markers. Average peak scaphoid interfragmentary motions due to
      transverse fracture and wedge osteotomy were statistically compared (P<0.05) to
      intact. FINDINGS: The accuracy of our computed interfragmentary motions was +/-
      0.24 mm for translation and +/- 0.54 degrees  for rotation. Average peak
      interfragmentary motions due to fracture ranged between 0.9 mm to 1.9 mm for
      translation and 5.3 degrees  to 10.8 degrees  for rotation. Significant increases
      in interfragmentary motions were observed in volar/dorsal translations and
      flexion/extension due to transverse fracture and in separation and rotations in
      all 3 motion planes due to wedge osteotomy. INTERPRETATION: Comparison of our
      results with data from previous in vitro and in vivo biomechanical studies
      indicates a wide range of peak interfragmentary rotations due to scaphoid
      fracture, from 4.6 degrees  up to 30 degrees , with peak interfragmentary
      translations on the order of several millimeters. Significant interfragmentary
      motions, indicating clinical instability, likely occur due to physiologic flexion
      extension of the wrist in those with transverse scaphoid fracture with or without
      volar bone loss.

PMID- 24331862
TI  - Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT.
AB  - PURPOSE: Substantial organ motion and tumor shrinkage occur during radiotherapy
      for cervix cancer. IMRT planning studies have shown that the quality of radiation
      delivery is influenced by these anatomical changes, therefore the adaptation of
      treatment plans may be warranted. Image guidance with off-line replanning, i.e.
      hybrid-adaptation, is recognized as one of the most practical adaptation
      strategies. In this study, we investigated the effects of soft tissue image
      guidance using on-line MR while varying the frequency of off-line replanning on
      the adaptation of cervix IMRT. MATERIALS AND METHOD: 33 cervical cancer patients
      underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of
      33 were identified in a previous retrospective adaptive planning study, in which
      the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not
      acceptable given single off-line IMRT replan using a 3mm PTV margin with bone
      matching. These 5 patients and a randomly selected 10 patients from the remaining
      28 patients, a total of 15 patients of 33, were considered in this study. Two
      matching methods for image guidance (bone to bone and soft tissue to dose matrix)
      and three frequencies of off-line replanning (none, single, and weekly) were
      simulated and compared with respect to target coverage (cervix, GTV, lower
      uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV)
      and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time)
      and benefit (target coverage) were analyzed for comparison. RESULTS: Hybrid
      adaptation (image guidance with off-line replanning) significantly enhanced
      target coverage for both 5 difficult and 10 standard cases. Concerning image
      guidance, bone matching was short of delivering enough doses for 5 difficult
      cases even with a weekly off-line replan. Soft tissue image guidance proved
      successful for all cases except one when single or more frequent replans were
      utilized in the difficult cases. Cost and benefit analysis preferred (soft
      tissue) image guidance over (frequent) off-line replanning. CONCLUSIONS: On-line
      MRI based image guidance (with combination of dose distribution) is a crucial
      element for a successful hybrid adaptive radiotherapy. Frequent off-line
      replanning adjuvantly enhances adaptation quality.

PMID- 24331864
TI  - Non-specific task force criteria ECG presentation often provide the diagnosis of
      malignant arrhythmogenic right ventricular cardiomyopathy.

PMID- 24331863
TI  - Ischemic heart disease in systemic inflammatory diseases. An appraisal.
AB  - Systemic inflammatory diseases are inflammatory syndromes that are associated
      with increased cardiovascular morbidity and mortality. The link between
      inflammatory and cardiovascular diseases can be attributed to coexistence of
      classical risk factors and of inflammatory mechanisms activated in systemic
      inflammatory diseases and involving the immune system. Yet, clinical implications
      of these findings are not entirely clear and deeper knowledge and awareness of
      cardiac involvement in inflammatory diseases are necessary. The aims of this
      review are to summarize cardiac involvement in systemic inflammatory diseases and
      to identify areas where evidence is currently lacking that deserve further
      investigation in the future. 

PMID- 24331865
TI  - Renal denervation and hypertension resistant drug treatment in patient with renal
      artery accessory.

PMID- 24331866
TI  - Left radial access for percutaneous coronary procedures: from neglected to
      performer? A meta-analysis of 14 studies including 7,603 procedures.
AB  - BACKGROUND: Radial artery is currently the preferred access route for
      percutaneous coronary procedures. The major reason for its widespread use is the
      higher safety as compared to femoral artery access. Initially most centers have
      preferred the right radial artery. However, an advantage has been hypothesized
      for the left radial access especially for the more favorable vascular anatomy.
      For this reason, the aim of the present meta-analysis was to compare procedural
      performance of left and right radial artery access for percutaneous coronary
      interventions. METHODS: We performed a meta-analysis of all available studies
      comparing right radial access and left radial access for coronary procedures.
      Corrected standardized mean difference (Hedges' g) and odds ratios (OR) were used
      to estimate the mean effect respectively for continuous variables and
      frequencies. RESULTS: The present analysis includes 14 studies with 7603
      procedures. A statistically significant difference in the amount of contrast
      medium utilized for the procedure (0.12 [0.03-0.21], p=0.007), in fluoroscopy
      time (0.16 [0.06-0.25], p=0.001) and in total procedural time (0.22 [0.11; 0.33],
      p<0.001) was observed in favor of the left radial access. At the same time, no
      significant difference in the rate of procedural failure was observed between the
      right and the left radial access routes (OR=1.01 [0.70-1.47], p=0.942).
      CONCLUSIONS: Left radial access is associated to a modest yet significant
      reduction in fluoroscopy time, procedural time and in the amount of contrast
      medium administered, while failure rate was similar between right and left radial
      approaches.

PMID- 24331867
TI  - Cardiovascular magnetic resonance imaging in asymptomatic patients with
      connective tissue disease and recent onset left bundle branch block.
AB  - BACKGROUND-AIM: Recent LBBB in connective tissue diseases (CTDs) is challenging,
      due to high incidence of underlying pathology that may remain undetected, due to
      limitations of imaging tests. We hypothesized that cardiovascular magnetic
      resonance (CMR) may be of diagnostic value in CTDs with recent LBBB and normal
      echocardiogram. PATIENTS-METHODS: 26 CTDs, aged 32 +/- 7 yrs (19 F) and 26
      controls without CTDs, aged 60 +/- 4 yrs (10 F) with recent LBBB and normal echo
      were evaluated by CMR. The CTDs included 6 sarcoidosis (SRC), 4 systemic
      sclerosis (SSc), 6 systemic lupus erythematosus (SLE), 6 rheumatoid arthritis
      (RA) and 4 inflammatory myopathies (IM). CMR was performed by 1.5T. LVEF, T2
      ratio (oedema imaging) and late gadolinium enhancement (LGE) (fibrosis imaging)
      were evaluated. Acute and chronic lesions were characterised by T2>2 and positive
      LGE and T2<2 and positive LGE, respectively. According to LGE, lesions were
      characterised as diffuse subendo-, subepicardial/intramural not following and
      subendocardial/transmural following the distribution of coronaries, indicative of
      vasculitis, myocarditis and myocardial infarction, respectively. RESULTS: CTDs
      were younger (p<0.001), with higher incidence of abnormal CMR (42.31 vs 30.77%,
      p=NS), including dilated cardiomyopathy (11.54%), diffuse subendocardial fibrosis
      (11.54%), myocardial infarction (7.69%) and acute myocarditis (11.54%) vs dilated
      cardiomyopathy (19.23%), myocardial infarction (7.69%) and acute myocarditis
      (3.85%), detected in non-CTDs. CONCLUSIONS: In CTDs with recent LBBB, CMR
      documented acute and chronic cardiac pathology, particularly myocarditis. CMR
      should be considered as an adjunct to conventional diagnostic workup in both
      patient groups, more so in CTDs.

PMID- 24331868
TI  - Role of human papillomavirus in non-oropharyngeal head and neck cancers.
AB  - Accurate estimates of the fraction of head and neck cancer (HNC) attributable to
      human papillomavirus (HPV) infection are essential to predict the effectiveness
      of interventions based on vaccination against HPV or HPV-testing. In addition, if
      supported by currently on-going clinical trials, attribution of a HNC to HPV may
      allow better and less toxic treatments. Here we focused on studies in which the
      prevalence of molecular and serological HPV markers was similarly assessed in
      oropharyngeal and non-oropharyngeal HNC. Large data on HPV DNA detection by PCR
      and p16 expression in HNC biopsies suggests that the probability of a cancer of
      the oral cavity, larynx, and hypopharynx being attributable to HPV is at least 5
      fold lower than that for oropharyngeal cancer. Seropositivity for HPV16 E6 or E7
      shows larger differences across sites, but findings vary between studies. Because
      HPV DNA and p16 detection lack specificity, and E6 and E7 antibody detection
      lacks sensitivity, these tests are not totally satisfactory. Limited data on in
      situ hybridization or HPV E6/E7 mRNA, mainly from the United States, suggests
      that HPV-attributable HNC is rare in the oral cavity (~3%), larynx (~7%), and
      hypopharynx (~0%). Data on HPV in other rarer HNCs are extremely limited and
      essentially negative. Available data do not allow the establishment of the way
      HPV infection and tobacco may interact in non-oropharyngeal HNC. The exclusion of
      oropharynx as a site of tumor origin and the identification of robust
      fingerprints of HPV-driven carcinogenesis are the priorities to improve the
      estimate of HPV-attributable non-oropharyngeal HNC. 

PMID- 24331869
TI  - Misunderstandings about attenuated psychosis syndrome in the DSM-5.

PMID- 24331870
TI  - Association between prefrontal hemodynamic responses during a cognitive task and
      subjective quality of life in schizophrenia.

PMID- 24331871
TI  - Impaired network stability in schizophrenia revealed by TMS perturbations.

PMID- 24331872
TI  - The AirtraqTM laryngoscope as a first choice for parturients with an expected
      difficult airway.

PMID- 24331873
TI  - The impact of greenhouse vegetable farming duration and soil types on
      phytoavailability of heavy metals and their health risk in eastern China.
AB  - Heavy metal contamination in vegetables from greenhouse vegetable production
      (GVP) in China requires major attention. For GVP sustainability at a large
      regional level, 441 surface GVP soil and 132 corresponding greenhouse vegetable
      samples were collected from six typical GVP bases in eastern China to
      systematically evaluate the impact of GVP duration and soil types (Anthrosols and
      Cambosols) on phytoavailability of four major metals, Cd, Cu, Zn, and Pb, and
      their health risk. The results revealed high Cd accumulation in leaf vegetables
      grown in Anthrosols, which might pose potential health risk. Regardless of soil
      types in the study region, greenhouse farming lowered soil pH and enhanced metal
      availability with rising GVP duration, which might exacerbate Cd
      phytoavailability and vegetable Cd contamination as well as potential health
      risk. Also, increased GVP soil organic matter contents over time, found in some
      locations, affected crop-depending Cu and Zn uptakes. Furthermore, due to GVP,
      the annual decrease rate of soil pH and increase rates of soil available metal
      concentrations were generally much greater in Anthrosols than those in Cambosols,
      which contributed a lot to high Cd uptake by leaf vegetables grown in Anthrosols
      and their potential health risk. From sustainable GVP perspective, fertilization
      strategy with reduced frequency and rate is especially important and effective
      for abating soil and vegetable contamination by heavy metals under greenhouse
      farming. 

PMID- 24331874
TI  - Permanganate gel (PG) for groundwater remediation: compatibility, gelation, and
      release characteristics.
AB  - Permanganate (MnO4(-)) is a strong oxidant that is widely used for treating
      chlorinated ethylenes in groundwater. This study aims to develop hyper-saline
      MnO4(-) solution (MnO4(-) gel; PG) that can be injected into aquifers via wells,
      slowly gelates over time, and slowly release MnO4(-) to flowing water. In this
      study, compatibility and miscibility of gels, such as chitosan, aluminosilicate,
      silicate, and colloidal silica gels, with MnO4(-) were tested. Of these gels,
      chitosan was reactive with MnO4(-). Aluminosilicates were compatible but not
      readily miscible with MnO4(-). Silicates and colloidal silica were both
      compatible and miscible with MnO4(-), and gelated with addition of KMnO4
      granules. Colloidal silica has low initial viscosity (<15cP), exhibited delayed
      gelation characteristics with the lag times ranging from 0 to 200min. Release of
      MnO4(-) from the colloidal silica-based PG gel occurred in a delayed fashion,
      with maximum duration of 24h. These results suggested that colloidal silica can
      be used to create PG or delayed-gelling forms containing other oxidants which can
      be used for groundwater remediation. 

PMID- 24331875
TI  - Concurrent trajectories of BMI and mental health patterns in emerging adulthood.
AB  - Affective disorders and weight status have been consistently linked in childhood
      and adult research, and this comorbidity has synergistic effects leading to more
      severe health consequences. We map the co-development of these developmental
      processes in the U.S. National Longitudinal Survey of Youth - 1997 (NLSY97)
      cohort ages 15 to 27 to inform the targeting of public health interventions. We
      estimate profiles of youth mental health and weight status through parallel
      process growth mixture modeling within a person-centered framework controlling
      for race/ethnicity, gender, and poverty status. Fit statistics indicate a 5-class
      parallel process model for the concurrent trajectories of BMI and mental health.
      The concurrent trajectories model reveals latent class trajectories of "stable
      normal weight, stable good mental health" (82.2%); "consistently obese, stable
      good mental health" (6.8%); "overweight becoming obese, declining mental health"
      (5.6%); "stable normal weight, improving mental health" (3.3%); and "morbid
      obesity, stable good mental health" (2.1%). The risk of developmental
      trajectories of poor mental health and BMI outcomes is greater for females,
      blacks, Hispanics, and individuals living below the poverty line. These results
      should help public health professionals to better target subpopulations
      approaching or already experiencing developmental pathways of risk for poor
      mental health and weight comorbidities. Multilevel investigation of lifestyle and
      contextual factors will foster further refinement of public health interventions.

PMID- 24331876
TI  - Immigrant health, place effect and regional disparities in Canada.
AB  - The paper addresses a critically important area in Canadian immigration and
      health from both a social and a spatial perspective. It employs multilevel and
      contextual approaches to examine the social determinants of immigrant health as
      well as the place effects on self-reported health at a regional and neighborhood
      scale. The data come from the raw microdata file of the 2005-10 Canadian
      Community Health Survey (a random national health survey) and the publicly
      available Canadian Marginalization index based on the 2006 Census. Three
      populations are compared: Canadian-born, overall foreign-born, and Chinese
      immigrants. The results suggest various degrees of association between self
      reported health, individual and lifestyle behavioral characteristics, and
      neighborhood material deprivation and ethnic concentration in census tracts.
      These factors contribute differently to the reported health of Chinese
      immigrants, Canada's largest recent immigrant group. A healthy immigrant effect
      is partially evident in the overall foreign-born population, but appears to be
      relatively weak in Chinese immigrants. For all groups, neighborhood deprivation
      moderately increases the likelihood of reporting poor health. Ethnic
      concentration negatively affects self-rated health, with the exception of the
      slight protective effect of Chinese-specific ethnic density in census tracts. The
      multilevel models reveal significant area inequalities across Census Metropolitan
      Areas/Census Agglomerations in risk of reporting unhealthy status, with greater
      magnitude in the foreign-born population. The vast regional variations in health
      among Chinese immigrants should be interpreted carefully due to the group's heavy
      concentration in large cities. The study contributes to the literature on
      ethnicity and health by systematically incorporating neighborhood contextual
      effects in modeling the social determinants of immigrant health status. It fills
      a gap in the literature on neighborhoods and health by focusing on ethnically
      disparate groups rather than on the general population. By revealing regional
      disparities in health, the paper adds a spatial perspective to the work on
      immigrant health. 

PMID- 24331877
TI  - Finding the right interactional temperature: do colder patients need more warmth
      in physician communication style?
AB  - Being aware of which communication style should be adopted when facing more
      difficult patients is important for physicians; it can help prevent patient
      reactions of dissatisfaction, mistrust, or non-adherence that can be detrimental
      to the process of care. Past research suggests that less agreeable patients are
      especially critical towards, and reactive to, their physician's communication
      style, compared to more agreeable patients. On the basis of the literature, we
      hypothesized that less agreeable patients would react more negatively than
      agreeable patients to lower levels of affiliativeness (i.e., warmth,
      friendliness) in the physicians, in terms of satisfaction with the physician,
      trust in the physician, and determination to adhere to the treatment. Thirty-six
      general practitioners (20 men/16 women) working in their own practice in
      Switzerland were filmed while interacting with 69 patients (36 men/33 women) of
      different ages (M = 50.7; SD = 18.19; range: 18-84) and presenting different
      medical problems (e.g., back pain, asthma, hypertension, diabetes). After the
      medical interview, patients filled in questionnaires measuring their satisfaction
      with the physician, their trust in the physician, their determination to adhere
      to the treatment, and their trait of agreeableness. Physician affiliativeness was
      coded on the basis of the video recordings. Physician gender and dominance,
      patient gender and age, as well as the gravity of the patient's medical condition
      were introduced as control variables in the analysis. Results confirmed our
      hypothesis for satisfaction and trust, but not for adherence; less agreeable
      patients reacted more negatively (in terms of satisfaction and trust) than
      agreeable patients to lower levels of affiliativeness in their physicians. This
      study suggests that physicians should be especially attentive to stay warm and
      friendly with people low in agreeableness because those patients' satisfaction
      and trust might be more easily lowered by a cold or distant physician
      communication style.

PMID- 24331878
TI  - Cross-national differences in the gender gap in subjective health in Europe: does
      country-level gender equality matter?
AB  - Multiple studies have found that women report being in worse health despite
      living longer. Gender gaps vary cross-nationally, but relatively little is known
      about the causes of comparative differences. Existing literature is inconclusive
      as to whether gender gaps in health are smaller in more gender equal societies.
      We analyze gender gaps in self-rated health (SRH) and limiting longstanding
      illness (LLI) with five waves of European Social Survey data for 191,104
      respondents from 28 countries. We use means, odds ratios, logistic regressions,
      and multilevel random slopes logistic regressions. Gender gaps in subjective
      health vary visibly across Europe. In many countries (especially in Eastern and
      Southern Europe), women report distinctly worse health, while in others (such as
      Estonia, Finland, and Great Britain) there are small or no differences. Logistic
      regressions ran separately for each country revealed that individual-level
      socioeconomic and demographic variables explain a majority of these gaps in some
      countries, but contribute little to their understanding in most countries. In yet
      other countries, men had worse health when these variables were controlled for.
      Cross-national variation in the gender gaps exists after accounting for
      individual-level factors. Against expectations, the remaining gaps are not
      systematically related to societal-level gender inequality in the multilevel
      analyses. Our findings stress persistent cross-national variability in gender
      gaps in health and call for further analysis. 

PMID- 24331879
TI  - Elective surgical patients' narratives of hospitalization: the co-construction of
      safety.
AB  - This research explores how elective surgical patients make sense of their
      hospitalization experiences. We explore sensemaking using longitudinal narrative
      interviews (n=72) with 38 patients undergoing elective surgical procedures
      between June 2010 and February 2011. We consider patients' narratives, the
      stories they tell of their prior expectations, and subsequent post-surgery
      experiences of their care in a United Kingdom (UK) hospital. An emergent pre
      surgery theme is that of a paradoxical position in which they choose to make
      themselves vulnerable by agreeing to surgery to enhance their health, this
      necessitating trust of clinicians (doctors and nurses). To make sense of their
      situation, patients draw on technical (doctors' expert knowledge and skills),
      bureaucratic (National Health Service as a revered institution) and ideological
      (hospitals as places of safety), discourses. Post-operatively, themes of 'chaos'
      and 'suffering' emerge from the narratives of patients whose pre-surgery
      expectations (and trust) have been violated. Their stories tell of unmet
      expectations and of inability to make shared sense of experiences with clinicians
      who are responsible for their care. We add to knowledge of how patients play a
      critical part in the co-construction of safety by demonstrating how patient
      clinician intersubjectivity contributes to the type of harm that patients
      describe. Our results suggest that approaches to enhancing patients' safety will
      be limited if they fail to reflect patients' involvement in the negotiated
      process of healthcare. We also provide further evidence of the contribution
      narrative inquiry can make to patient safety. 

PMID- 24331880
TI  - Metropolitan residential segregation and very preterm birth among African
      American and Mexican-origin women.
AB  - Residential segregation is associated with poor health-including poor birth
      outcomes-among African Americans in US cities and metropolitan areas. However,
      the few existing studies of this relationship among Mexican-origin women have
      produced mixed results. In this study, the relationship between segregation and
      very preterm birth was examined with National Center for Health Statistics (NCHS)
      data on singleton births to African American women (n = 400,718) in 238
      metropolitan areas and to Mexican-origin women (n = 552,382) in 170 metropolitan
      areas. The study evaluated 1) whether residential segregation is positively
      associated with very preterm birth among both African American and Mexican-origin
      women and 2) if so, whether exposure to neighborhood poverty accounts for these
      associations. Results from multi-level analysis indicate that residential
      segregation is positively associated with very preterm birth among both groups of
      women. However, this association is robust across different measures of
      segregation only for African Americans. Conversely, differences across
      metropolitan areas in average levels of exposure to neighborhood poverty account
      for the positive association between segregation and very preterm birth among
      Mexican-origin women, but not among African American women.

PMID- 24331881
TI  - Does corruption undermine trust in health care? Results from public opinion polls
      in Croatia.
AB  - Health and health care provision are one of the most important topics in public
      policy, and often a highly debated topic in the political arena. The importance
      of considering trust in the health care sector is highlighted by studies showing
      that trust is associated, among others, with poor self-related health, and poorer
      health outcomes. Similarly, corruption has shown to create economic costs and
      inefficiencies in the health care sector. This is particularly important for a
      newly democratized country such as Croatia, where a policy responsive government
      indicates a high level of quality of democracy (Roberts, 2009) and where a legacy
      of corruption in the health care sector has been carried over from the previous
      regime. In this study, I assess the relationship between health care corruption
      and trust in public health care and hypothesize that experience with health care
      corruption as well as perception of corruption has a negative effect on trust in
      public care facilities. Data were collected in two surveys, administered in 2007
      and 2009 in Croatia. Experience with corruption and salience with corruption has
      a negative effect on trust in public health care in the 2007 survey, but not in
      the 2009 survey. While the results are mixed, they point to the importance of
      further studying this relationship. 

PMID- 24331882
TI  - Effects of education on cognition at older ages: evidence from China's Great
      Famine.
AB  - This paper explores whether educational attainment has a cognitive reserve
      capacity in elder life. Using pilot data from the China Health and Retirement
      Longitudinal Study (CHARLS), we examined the impact of education on cognitive
      abilities at old ages. OLS results showed that respondents who completed primary
      school obtained 18.2 percent higher scores on cognitive tests than those who did
      not. We then constructed an instrumental variable (IV) by leveraging China's
      Great Famine of 1959-1961 as a natural experiment to estimate the causal effect
      of education on cognition. Two-stage least squares (2SLS) results provided sound
      evidence that completing primary school significantly increases cognition scores,
      especially in episode memory, by almost 20 percent on average. Moreover,
      Regression Discontinuity (RD) analysis provides further evidence for the causal
      interpretation, and shows that the effects are different for the different
      measures of cognition we explored. Our results also show that the Great Famine
      can result in long-term health consequences through the pathway of losing
      educational opportunities other than through the pathway of nutrition
      deprivation. 

PMID- 24331883
TI  - Spousal influence on mammography screening: a life course perspective.
AB  - Recently, researchers have challenged the basic tenet that marriage is
      universally protective for all individuals. We scrutinize socio-economic
      differences between married couples to shed light on the mechanisms underlying
      the effects of marriage. We introduce the life course perspective to investigate
      if differences in positive health behavior between couples are related to their
      early life conditions. Within the theoretical framework of cultural health
      capital, we hypothesize that the accumulation of cultural health capital proceeds
      at the marriage level when partners provide each other with health-related
      information and norms. For this purpose, we examine the influence of the
      childhood preventive health care behavior of both wives and husbands on the
      initiation of mammography screening for a sample of Belgian women (N = 734).
      Retrospective life histories of both partners are provided by the Survey of
      Health, Ageing and Retirement (SHARE) and are examined by means of event history
      analysis. The results show that a partner's cultural health capital affects the
      initiation of mammography screening by a woman in later life, even after her own
      cultural health capital and traditional measures of socio-economic status (SES)
      are taken into account. In line with cumulative advantage theory, it seems that
      inequalities in cultural health capital are accumulated at the marriage level. In
      order to shed further light on the spousal influence on health behavior,
      researchers should revert to early life in order to discern the attribution of
      premarital and marital conditions.

PMID- 24331884
TI  - Village characteristics and health of rural Chinese older adults: examining the
      CHARLS Pilot Study of a rich and poor province.
AB  - Community (or village) characteristics have received growing attention as
      researchers have sought factors affecting health. This study examines the
      association between a variety of environmental, economic, and social village
      characteristics and health of Chinese older rural adults with health measured in
      terms of physical limitations. The Chinese Health and Retirement Longitudinal
      Survey (CHARLS) Pilot Study data were used. Older villagers from a low-income
      province (Gansu) and a relatively wealthy province (Zhejiang) were surveyed
      between July and September, 2008. The sample included 1267 respondents in 73
      villages age 45 and older. The relationship between a variety of village
      characteristics and physical limitations of older adults was examined using
      negative binomial regression (NBR) with standard errors adjusted to account for
      non-independence of respondents in a village. A comparison of means/percentages
      shows that Gansu and Zhejiang were significantly different on the dependent and
      most independent variables. The NBR models show that at the personal-level,
      decreased risk of physical limitations was associated with being male, less than
      60 years old, married, higher in education, and higher in household expenditures
      (proxy for income). At the village-level, decreased risk of limitations was
      associated with a continuous supply of electricity, not using coal in the
      household, the existence of a sewage system, low cost of electricity, and village
      wealth. Decreased risk of physical limitations was also associated with various
      characteristics of China's New Cooperative Medical Scheme (NCMS), an insurance
      program for rural older adults. Policy implications for improved health of rural
      older adults include: (1) continued use of China's NCMS, (2) establishment of
      village sewage systems, (3) ending the use of coal in the home, and (4) increased
      educational opportunities focused on health. 

PMID- 24331885
TI  - An exploratory study of knowledge brokering in hospital settings: facilitating
      knowledge sharing and learning for patient safety?
AB  - This paper reports on an exploratory study of intra-organisational knowledge
      brokers working within three large acute hospitals in the English National Health
      Services. Knowledge brokering is promoted as a strategy for supporting knowledge
      sharing and learning in healthcare, especially in the diffusion of research
      evidence into practice. Less attention has been given to brokers who support
      knowledge sharing and learning within healthcare organisations. With specific
      reference to the need for learning around patient safety, this paper focuses on
      the structural position and role of four types of intra-organisational brokers.
      Through ethnographic research it examines how variations in formal role, location
      and relationships shape how they share and support the use of knowledge across
      organisational and occupational boundaries. It suggests those occupying hybrid
      organisational roles, such as clinical-managers, are often best positioned to
      support knowledge sharing and learning because of their 'ambassadorial' type
      position and legitimacy to participate in multiple communities through dual
      directed relationships. 

PMID- 24331886
TI  - Service provision for autism in mainland China: preliminary mapping of service
      pathways.
AB  - Few data on healthcare services for individuals with Autism Spectrum Conditions
      (ASC) are available from mainland China. This article is based on findings from
      69 semi-structured interviews with parents of children with ASC in three
      intervention centres. The respondents are from 19 regions in mainland China. A
      service-mapping questionnaire containing 50 questions is developed and used as an
      interview schedule for service mapping. The pathway to diagnosis and intervention
      for children with ASC is presented according to parents' experience. The findings
      report considerable delay along the pathway which may be partly due to the under
      developed service system. Several cultural issues are identified which may also
      contribute to the delay, such as the perception of mental illness, folk beliefs
      equating delayed development of language skills in early childhood with future
      high intelligence, and the state-imposed one-child policy. Delays in recognising
      ASC and a lack of support are also considered to be associated with the
      considerable financial burden placed on parents of children with ASC in mainland
      China. 

PMID- 24331887
TI  - Technology identity: the role of sociotechnical representations in the adoption
      of medical devices.
AB  - This study explored the sociotechnical influences shaping the naturally-occurring
      adoption and non-adoption of device technologies in the UK's National Health
      Service (NHS), amid increasing policy interest in this area. The study was
      informed by Science and Technology Studies and structuration and Actor Network
      Theory perspectives, drawing attention to the performative capacities of the
      technology alongside human agentic forces such as agendas and expectations, in
      the context of structural and macro conditions. Eight technologies were studied
      using a comparative ethnographic case study design and purposive and snowball
      sampling to identify relevant NHS, academic and industry participants. Data were
      collected between May 2009 and February 2012, included in-depth interviews,
      conference observations and printed and web-based documents and were analysed
      using constructivist grounded theory methods. The study suggests that while
      adoption decisions are made within the jurisdiction of healthcare organisations,
      they are shaped within a dynamic and fluid 'adoption space' that transcends
      organisational and geographic boundaries. Diverse influences from the industry,
      health care organisation and practice, health technology assessment and policy
      interact to produce 'technology identities.' Technology identities are composite
      and contested attributes that encompass different aspects of the technology
      (novelty, effectiveness, utility, risks, requirements) and that give a
      distinctive character to each. We argue that it is these socially constructed and
      contingent heuristic identities that shape the desirability, acceptability,
      feasibility and adoptability of each technology, a perspective that policy must
      acknowledge in seeking to intervene in health care technology adoption. 

PMID- 24331888
TI  - A mixed-method study of expert psychological evidence submitted for a cohort of
      asylum seekers undergoing refugee status determination in Australia.
AB  - The levels of exposure to conflict-related trauma and the high rates of mental
      health impairment amongst asylum seekers pose specific challenges for refugee
      decision makers who lack mental health training. We examined the use of
      psychological evidence amongst asylum decision makers in New South Wales,
      Australia, drawing on the archives of a representative cohort of 52 asylum
      seekers. A mixed-method approach was used to examine key mental health issues
      presented in psychological reports accompanying each asylum application,
      including key documents submitted for consideration of asylum at the primary and
      review levels. The findings indicated that the majority of decision makers at
      both levels did not refer to psychological evidence in their decision records.
      Those who did, particularly in the context of negative decisions, challenged the
      expert findings and rejected the value of such evidence. Asylum seekers
      exhibiting traumatic stress symptoms such as intrusive thoughts and avoidance, as
      well as memory impairment, experienced a lower acceptance rate than those who did
      not across the primary and review levels. The findings raise concern that trauma
      affected asylum seekers may be consistently disadvantaged in the refugee decision
      making process and underscore the need to improve the understanding and use of
      mental health evidence in the refugee decision-making setting. The study findings
      have been used to develop a set of guidelines to assist refugee decision makers,
      mental health professionals and legal advisers in improving the quality and use
      of psychological evidence within the refugee decision-making context. 

PMID- 24331889
TI  - Does loneliness mediate the relation between social support and cognitive
      functioning in later life?
AB  - Research in gerontology has demonstrated mixed effects of social support on
      cognitive decline and dementia: Social support has been shown to be protective in
      some studies, but not in others. Moreover, little is known about the underlying
      mechanisms between social support and cognitive functioning. We investigate one
      of the possible mechanisms, and argue that subjective appraisals rather than
      received amounts of social support affect cognitive functioning. Loneliness is
      seen as an unpleasant experience that occurs when a person's network of
      relationships is felt to be deficient in some important way. As such, loneliness
      describes the extent to which someone's needs are not being met and thus provides
      a subjective assessment of support quality. We expect that receiving instrumental
      and emotional support reduces loneliness, which in turn preserves cognitive
      functioning. Data are from the Longitudinal Aging Study Amsterdam (LASA) and
      include 2255 Dutch participants aged 55-85 over a period of six years.
      Respondents were measured every three years. Cognitive functioning was assessed
      with the Mini-Mental State Examination (MMSE), the Coding Task, and the Raven's
      Coloured Progressive Matrices. The analytical approach comprised latent growth
      mediation models. Frequent emotional support related to reduced feelings of
      loneliness and better cognitive functioning. Increases in emotional support also
      directly enhanced cognitive performance. The protective effect of emotional
      support was strongest amongst adults aged 65 years and older. Increase in
      instrumental support did not buffer cognitive decline, instead there were
      indications for faster decline. After ruling out the possibility of reversed
      causation, we conclude that emotional support relationships are a more powerful
      protector of cognitive decline than instrumental support relationships. 

PMID- 24331890
TI  - Social norms and attitudes linked to waterpipe use in the Eastern Mediterranean
      Region.
AB  - Waterpipe tobacco smoking (WTS) is on the rise globally, particularly among
      vulnerable populations such as youth and women. Increasing knowledge about
      toxicant yield from waterpipe tobacco and deleterious health effects points to
      the potential for a health epidemic. WTS is often viewed as a safe alternative to
      cigarette smoking. Though the original objective of the research was to explore
      the social norms and attitudes that lead to waterpipe being a more acceptable
      form of tobacco smoking for women than cigarettes in the Eastern Mediterranean
      Region, the use of a qualitative research methodology resulted in rich data that
      helped to understand more generally the phenomenon of waterpipe smoking. Both
      focus group discussions (FGDs) and key informant interviews were used.
      Participants were recruited to represent genders, various age groups,
      socioeconomic status, waterpipe smoking status, and residents of urban and rural
      areas. A total of 81 FGDs and 38 in-depth interviews were conducted in 2007.
      Thematic analysis was used to analyze the transcripts. A total of ten themes
      emerged: socio-cultural norms, gender differences, motivation to smoke, sensory
      characteristics of waterpipe, metaphors, consumerism, indicators of dependence,
      comparison between cigarettes and waterpipe, health effect of smoking, and
      intervention. Results indicated that WTS has socio-cultural dynamics associated
      with it that are far more pronounced than health considerations. An increased
      socio-cultural acceptability, the perceived reduced harm and the advent of the
      fruity Moassel tobacco are among the many reasons for WTS acceptability. Findings
      point to the need for a unified strategy to address this health issue at all
      levels of the ecological framework and have important implications for future
      policy and practice. 

PMID- 24331891
TI  - Caregiving appraisal in schizophrenia: a study from India.
AB  - This study evaluated caregiving experience in the caregivers of patients with
      schizophrenia within the framework of the stress-appraisal-coping model. By
      purposive random sampling, 100 Indian patients with schizophrenia and their
      primary caregivers were assessed. The patients were assessed on Positive and
      Negative Symptom Scale (PANSS). Caregivers completed the Scale for Positive
      Aspects of Caregiving Experience (SPACE), Involvement Evaluation Questionnaire
      (IEQ), Family Burden Interview (FBI) Schedule, Coping Checklist, Social Support
      Questionnaire, and General Health Questionnaire (GHQ-12). Path analysis showed
      that psychological morbidity is mainly determined by subjective experience of
      burden, which in turn is significantly influenced by severity of psychopathology,
      time spent per day (in hours) in caregiving and the coping strategies used.
      Although coping strategies and PANSS do influence objective burden, objective
      burden itself has no influence on the level of psychological morbidity. Total
      PANSS score has no direct influence on subjective burden, but acts indirectly
      through total time spent in caregiving and coping. Caregiver's gain in positive
      experiences on SPACE scale positively influences subjective burden. The present
      findings suggest that better control of patients' symptoms would lead to less
      demand on the caregivers in the form of time and strain on coping abilities and
      would thus reduce subjective burden and psychological morbidity in the
      caregivers. 

PMID- 24331892
TI  - Moral mediation in interpreted health care consultations.
AB  - This paper reports on the moral work done in routine diabetes review
      consultations in primary care with nurses. Consultations with fluent English
      speakers are compared with consultations where an interpreter was present,
      largely involving patients of Bangladeshi origin. The study setting was Tower
      Hamlets in London, where type 2 diabetes is particularly common. Existing
      research has shown some dissatisfaction with diabetes care amongst Bangladeshi
      patients, and studies of care providers in other locations suggest that they at
      times experience the care of this group as particularly challenging. Through
      analysis of video-recorded consultations recorded in 2010-2011 we shed light on
      possible reasons for these difficulties. The 12 non-English speakers often
      experienced difficulties in raising issues that concerned them, particularly if
      their interpreter did not translate their utterance because it was deemed to be
      unrelated to diabetes. These difficulties were not shared by the 24 fluent
      English speakers, who also found it easier to convey a positive moral reputation
      and to excuse behaviour that deviated from recommended self-management practices.
      Interpreters at times also acted as moral mediators. For example, where a
      participant in the consultation made statements that appeared to convey a
      negative moral judgement of an other participant, these would often go
      untranslated. Probably, neither health care providers nor patients are fully
      aware of the nature of their communication difficulties. Given this, interpreters
      possess considerable power to influence matters. Understanding the moral work of
      consultations is important in explaining the findings of other studies showing
      difficulties in the provision of diabetes care to people with limited English
      language skills. 

PMID- 24331893
TI  - An assessment of economic measures used in menorrhagia: a systematic review.
AB  - 'Menorrhagia', or heavy menstrual bleeding, is a common problem affecting women.
      The principal driver for treatment is women's experience of its interference in
      their lives, so a measure of quality of life (QoL) is increasingly used as the
      primary outcome to assess treatment success. QoL measures need to accurately
      reflect women's concerns as these measures are often used to inform resource
      allocation decisions within the healthcare service. Healthcare decision-makers
      often advocate the use of generic measures so as to achieve consistency when
      making decisions. Generic measures, by definition, have a broad focus on QoL in
      contrast to disease-specific measures that focus on dimensions of health relevant
      to the condition. We report a systematic review of studies that have either used
      or assessed economic outcome measures in menorrhagia, and present criteria for
      assessing which measure is the most appropriate. Studies including women
      presenting with menorrhagia, and using or assessing economic measures were sought
      by searching nine electronic databases. Fifty-six eligible studies were
      identified. A narrative synthesis was most suitable to the review question.
      Eleven studies assessed the psychometric properties of the outcome measures,
      twelve studies applied the measures in an economic evaluation, and thirty-three
      used them in effectiveness studies. Mixed results on the psychometric properties
      of the instruments were observed. Studies were often found to include both a
      disease-specific and a generic measure. We found no consensus on the most
      appropriate economic outcome measure to use when assessing the cost-effectiveness
      of treatment for menorrhagia. This is an important finding as QoL is the primary
      focus for treatment decisions. The cyclical nature of the condition has a large
      impact on the reliability and validity of outcome measurement. Alternative
      measures, such as willingness-to-pay, which embrace more than health and avoid
      standard recall periods should be explored. 

PMID- 24331895
TI  - Using programme budgeting and marginal analysis (PBMA) to set priorities:
      reflections from a qualitative assessment in an English Primary Care Trust.
AB  - In England from 2002 to 2013, Primary Care Trusts (PCTs) were responsible for
      commissioning healthcare for their local populations. The NHS has recently
      undergone rapid organisational change whereby clinicians have assumed
      responsibility for local commissioning decisions. This change in commissioning
      arrangements alongside the current financial pressures facing the NHS provides an
      impetus for considering the use of technical prioritisation methods to enable the
      identification of savings without having a detrimental effect on the health of
      the population. This paper reports on the design and implementation of a
      technical prioritisation method termed PBMA applied within NHS Plymouth, an
      English PCT responsible for commissioning services for a population of
      approximately 270,000. We evaluated the effectiveness of the process, the extent
      to which it was appropriate for local healthcare commissioning and whether it
      identified budget savings. Using qualitative research methodology, we found the
      process produced clear strategic and operational priorities for 2010/11,
      providing staff with focus and structure, and delivered a substantial planned
      reduction in hospital activity levels. Participants expressed satisfaction with
      the process. NHS Plymouth adhered to the PBMA process, although concerns were
      raised about the evidence for some priorities, decibel rationing, and a lack of
      robust challenge at priority-setting meetings. Further work is required to
      enhance participants' understanding of marginal analysis. Participants
      highlighted several external benefits, particularly in terms of cultural change,
      and felt the process should encompass the whole local health and social care
      community. This evaluation indicates that the prioritisation method was effective
      in producing priorities for NHS Plymouth, and that PBMA provides an appropriate
      method for allocating resources at a local level. In order for PBMA to identify
      savings, cultural and structural barriers to disinvestment must be addressed.
      These findings will interest other healthcare commissioners in developing their
      own approaches to priority-setting. 

PMID- 24331894
TI  - Inequalities in Croatian pupils' risk behaviors associated to socioeconomic
      environment at school and area level: a multilevel approach.
AB  - The socioeconomic inequality in pupils' risk behaviors has been the topic of many
      studies with quite contradictory findings. Furthermore, the role of socioeconomic
      environment has been analyzed much less often than the role of individual
      socioeconomic status (SES). This study examined the association between
      school/area-level socioeconomic environment and Croatian pupils' risk behaviors
      (tobacco use, drunkenness, cannabis use, early sexual initiation and fighting).
      Data from the WHO-Collaborative 'Health Behavior in School-aged Children' study
      conducted in Croatia in 2006 (1601 secondary schools' pupils, aged 15) and census
      data were used. Multilevel logistic regression analyses, adjusted by gender, were
      performed. The individual level of SES explained the majority of differences in
      all risk behaviors among adolescents. Differences in tobacco use, early sexual
      initiation and fighting were more closely attributed to school level than area
      level, which was more closely associated with differences in adolescent
      drunkenness and cannabis use. At the individual level, high individual SES was
      associated with higher probability for tobacco use and drunkenness compared to
      low individual SES. Furthermore, school heterogeneity (compared to school
      homogeneity) and medium school-level SES (compared to low school-level SES) were
      associated with higher probability for cannabis use. Compared to the most
      advanced schools (gymnasiums), attending the least advanced schools (industrial
      and crafts schools) was associated with higher probability for fighting. Compared
      to low area-level SES, medium area-level SES was associated with higher
      probability for cannabis use and fighting. Conclusively, it was found that low
      SES at individual, school and area levels, school homogeneity and advanced school
      attendance play a protective role against risk behaviors. To reduce inequalities
      in pupils' risk behaviors, there is a need for community and school-based
      programs that take into consideration not only individual SES but also school-
      and area-level socioeconomic circumstances. 

PMID- 24331896
TI  - Brain drain: Do economic conditions "push" doctors out of developing countries?
AB  - Health worker migration is an issue of first order concern in global health
      policy circles and continues to be the subject of much policy debate. In this
      paper, we contribute to the discussion by studying the impact of economic
      conditions on the migration of physicians from developing countries. To our
      knowledge, this is one of the first papers to do so. A major contribution of this
      paper is the introduction of a new panel dataset on migration to the US and the
      UK from 31 sub-Saharan Africa countries. The data spans the period 1975-2004.
      Using this data, we estimate the impact of changes in economic conditions on
      physician migration. In our preferred specification that allows for country
      specific time trends, we find that a temporary one percentage point decline in
      GDP per capita increases physician migration in the next period by approximately.
      3 percent. In our IV models a one percentage point decline in GDP per capita
      increases physician migration in the next period by between 3.4 and 3.6 percent.
      Overall, our results suggest a significant effect of developing country economic
      conditions on physician migration. 

PMID- 24331897
TI  - Social group memberships protect against future depression, alleviate depression
      symptoms and prevent depression relapse.
AB  - A growing body of research suggests that a lack of social connectedness is
      strongly related to current depression and increases vulnerability to future
      depression. However, few studies speak to the potential benefits of fostering
      social connectedness among persons already depressed or to the protective
      properties of this for future depression trajectories. We suggest that this may
      be in part because connectedness tends to be understood in terms of (difficult to
      establish) ties to specific individuals rather than ties to social groups. The
      current study addresses these issues by using population data to demonstrate that
      the number of groups that a person belongs to is a strong predictor of subsequent
      depression (such that fewer groups predicts more depression), and that the
      unfolding benefits of social group memberships are stronger among individuals who
      are depressed than among those who are non-depressed. These analyses control for
      initial group memberships, initial depression, age, gender, socioeconomic status,
      subjective health status, relationship status and ethnicity, and were examined
      both proximally (across 2 years, N = 5055) and distally (across 4 years, N =
      4087). Depressed respondents with no group memberships who joined one group
      reduced their risk of depression relapse by 24%; if they joined three groups
      their risk of relapse reduced by 63%. Together this evidence suggests that
      membership of social groups is both protective against developing depression and
      curative of existing depression. The implications of these results for public
      health and primary health interventions are discussed.

PMID- 24331898
TI  - Operationalising the capability approach for outcome measurement in mental health
      research.
AB  - Amartya Sen's multidimensional capability approach focuses on the importance of
      freedoms to be or do things people have reason to value. It is an alternative to
      standard utilitarian welfarism, the theoretical approach to quality-adjusted life
      years (QALYs) and cost-utility analyses. Despite the limitations of the utility
      approach in capturing non-health benefits and broader welfare inequalities, there
      have been very limited applications of the capability approach in the mental
      health context where these issues are imperative. We report the development and
      application of a multidimensional instrument, the OxCAP-MH, which aims to
      operationalise the capability approach for outcome measurement in mental health
      research. The study was carried out as part of an ongoing programme on community
      coercion experienced by service users with severe and enduring mental illness
      being treated using Community Treatment Orders. Capabilities data were collected
      at baseline in the OCTET RCT for 333 'revolving door' mental health service users
      who were in involuntary hospital treatment at the time of recruitment in England
      (2008-2011). The research focused on the identification of capabilities domains
      most affected by mental illness and their association with socio-demographic and
      clinical factors and other measures of well-being such as the EQ-5D and Global
      Assessment of Functioning (GAF) scales. The OxCAP-MH item response rate was 90%
      68%. There were significant correlations between service users' overall
      capability scores and the GAF, EQ-5D VAS and EQ-5D-3L utilities (corr = 0.249,
      0.514, 0.415, respectively). The most affected capability domains were: 'Daily
      activities', 'Influencing local decisions', 'Enjoying recreation', 'Planning
      one's life' and 'Discrimination'. Age had a mixed effect, while female service
      users and those with a primary diagnosis of schizophrenia or longer illness
      duration reported significantly lower capability scores. The results support the
      feasibility and validity of directly measuring human capabilities for the
      mentally ill and the potential for applying the approach to outcome measurement. 

PMID- 24331899
TI  - The impacts of marriage, cohabitation and dating relationships on weekly self
      reported physical activity in Germany: a 19-year longitudinal study.
AB  - Despite the increasing number of non-marital romantic relationships in developed
      countries, little is known about their effects on health-related behaviors. This
      paper examined the impact of relationship status (single, dating, cohabiting or
      married) on physical activity. Three possible mechanisms underlying this
      association were discussed: social control and support by the partner, time
      restrictions and the release from the marriage market. Data were obtained from
      the German Socio-Economic Panel (GSOEP), a random sample of individuals living in
      private households in Germany. Both random-effects and fixed-effects logit models
      were estimated. The random-effects analyses referred to 30,201 individuals and
      the fixed-effects analyses referred to 11,568 individuals who were observed for
      up to 19 years. After adjusting for age, measurement period and the presence of
      children, fixed-effects estimates showed reduced physical activity for each type
      of relationship for both men and women. The effects were strongest for married
      couples and weakest for dating couples, and remained similar after controlling
      for discretionary time. However, the effects found partly depended on age: for
      men, the negative impacts of cohabitation and marriage on physical activity
      became weaker with increasing age and shifted to positive impacts. For women, the
      negative effect of marriage on physical activity also decreased but stayed
      negative into old age. The results suggest that the release from the marriage
      market may cause the negative effects of relationships on physical activity.
      Social support and social control may play a role in older age, whereas the
      amount of discretionary time seems to be of minor importance for explaining
      relationship effects on physical activity. If the results will be validated by
      other studies there will be valuable implications for health promotion programs. 

PMID- 24331900
TI  - Potential effectiveness of anti-smoking advertisement types in ten low and middle
      income countries: do demographics, smoking characteristics and cultural
      differences matter?
AB  - Unlike high income countries, there is limited research to guide selection of
      anti-tobacco mass media campaigns in low and middle income countries, although
      some work suggests that messages emphasizing serious health harms perform better
      than other message types. This study aimed to determine whether certain types of
      anti-smoking advertisements are more likely to be accepted and perceived as
      effective across smokers in 10 low to middle income countries. 2399 18-34 year
      old smokers were recruited in Bangladesh, China, Egypt, India, Indonesia, Mexico,
      Philippines, Russia, Turkey and Vietnam to view and rate 10 anti-tobacco ads.
      Five ads were shown in all countries and five ads were chosen by country
      representatives, providing a total of 37 anti-smoking ads across all countries
      (10 graphic health effects ads, 6 simulated health effects, 8 emotional stories
      of health effects, 7 other health effects and 6 non-health effects). Smokers
      rated ads on a series of 5-point scales containing aggregated measures of Message
      Acceptance and Perceived Effectiveness. All ads and materials were translated
      into the local language of the testing regions. In multivariate analysis, graphic
      health effects ads were most likely to be accepted and perceived as effective,
      followed by simulated health effects ads, health effects stories, other health
      effects ads, and then non-health effects ads. Interaction analyses indicated that
      graphic health effects ads were less likely to differ in acceptance or perceived
      effectiveness across countries, gender, age, education, parental status and
      amount smoked, and were less likely to be affected by cultural differences
      between characters and contexts in ads and those within each country. Ads that
      did not emphasize the health effects of smoking were most prone to inconsistent
      impact across countries and population subgroups. Graphic ads about the negative
      health effects of smoking may be most suitable for wide population broadcast in
      low and middle income countries. 

PMID- 24331901
TI  - The effects of information, social and financial incentives on voluntary
      undirected blood donations: evidence from a field experiment in Argentina.
AB  - In many low- and middle-income countries blood donations per capita are
      substantially lower than in advanced economies. In these countries blood supply
      is mostly collected through directed donations from relatives and friends to
      individuals needing transfusions or to replace blood used in emergencies. The
      World Health Organization considers this method of blood supply inefficient
      compared to undirected voluntary donations. To examine methods to motivate
      undirected voluntary donations, we ran a large-scale, natural field experiment in
      Argentina, testing the effectiveness of information, social and financial
      incentives. We find that only higher-valued financial incentives generated more
      donations, increasing with the value of the reward. These incentives did not
      create adverse selection in the safety or usability of the donated blood. We
      discuss the implications of our findings for researchers interested in
      understanding motivations for pro-social behavior and for health agencies and
      policymakers concerned with the current and growing shortages in blood supply in
      low- and middle-income countries. 

PMID- 24331902
TI  - Ethics is for human subjects too: participant perspectives on responsibility in
      health research.
AB  - Despite the significant literature as well as energy devoted to ethical review of
      research involving human subjects, little attention has been given to
      understanding the experiences of those who volunteer as human subjects. Why and
      how do they decide to participate in research? Is research participation viewed
      as a form of social responsibility or as a way of obtaining individual benefits?
      What if anything do research subjects feel they are owed for participation? And
      what do they feel that they owe the researcher? Drawing on in-depth individual
      interviews conducted in 2006 and 2007 with 41 subjects who participated in a
      variety of types of health research in Canada, this paper focuses on subject
      perspectives on responsibility in research. Highlighting the range of ways that
      subjects describe their involvement in research and commitments to being a 'good'
      subject, we present a typology of narratives that sheds new light on the diverse
      meanings of research participation. These narratives are not mutually exclusive
      or prescriptive but are presented as ideal types typifying a set of circumstances
      and values. As such, they collectively illuminate a range of motivations
      expressed by human subjects as well as potential sources of vulnerability. The
      typology adds a new dimension to the literature in this area and has significant
      implications for researchers seeking more human-subject centred approaches to
      research recruitment and retention, as well as research ethics boards trying to
      better anticipate the perspectives of prospective participants. 

PMID- 24331903
TI  - "Differently normal" and "normally different": negotiations of female embodiment
      in women's accounts of 'atypical' sex development.
AB  - During recent decades numerous feminist scholars have scrutinized the two-sex
      model and questioned its status in Western societies and medicine. Along the same
      line, increased attention has been paid to individuals' experiences of atypical
      sex development, also known as intersex or 'disorders of sex development' (DSD).
      Yet research on individuals' experiences of finding out about their atypical sex
      development in adolescence has been scarce. Against this backdrop, the present
      article analyses 23 in-depth interviews with women who in their teens found out
      about their atypical sex development. The interviews were conducted during 2009
      2012 and the interviewees were all Swedish. Drawing on feminist research on
      female embodiment and social scientific studies on diagnosis, I examine how the
      women make sense of their bodies and situations. First, I aim to explore how the
      women construe normality as they negotiate female embodiment. Second, I aim to
      investigate how the divergent manners in which these negotiations are expressed
      can be further understood via the women's different access to a diagnosis.
      Through a thematic and interpretative analysis, I outline two negotiation
      strategies: the "differently normal" and the "normally different" strategy. In
      the former, the women present themselves as just slightly different from 'normal'
      women. In the latter, they stress that everyone is different in some manner and
      thereby claim normalcy. The analysis shows that access to diagnosis corresponds
      to the ways in which the women present themselves as "differently normal" and
      "normally different", thus shedding light on the complex role of diagnosis in
      their negotiations of female embodiment. It also reveals that the women make use
      of what they do have and how alignments with and work on norms interplay as
      normality is construed. 

PMID- 24331904
TI  - The relationship between three stages of job change and long-term sickness
      absence.
AB  - Although several researchers originally assumed that change always causes strain,
      a growing number of studies suggest that job change can have positive effects.
      However, the focus of these studies has generally been on subjective measures of
      satisfaction and well-being and rarely on health. Therefore, the purpose of the
      present study was to investigate how job change relates to long-term sickness
      absence during three stages: exit, entry, and normalization. Norwegian hospital
      employees, a low-unemployment group, were followed over a 6-year period as they
      moved in and out of different jobs. The study used fixed-effect methods to
      analyze changes in absence for each employee. The results show increased odds of
      long-term sickness absence during the 2 years prior to exiting an organization, a
      significant drop after the employee entered a new organization, and then a
      gradual increase in long-term sickness absence thereafter. After 2 years, the
      employee's odds of entering into long-term sickness absence were no longer
      significantly different from normal (i.e., the odds in months not related to job
      change). These findings on employee health are congruent with conclusions drawn
      from research on job satisfaction and well-being. 

PMID- 24331905
TI  - Do bonding and bridging social capital affect self-rated health, depressive mood
      and cognitive decline in older Japanese? A prospective cohort study.
AB  - Little is known regarding the longitudinal effects of bonding and bridging social
      capital on health. This study examined the longitudinal associations of bonding
      and bridging social capital with self-rated health, depressive mood, and
      cognitive decline in community-dwelling older Japanese. Data analyzed in this
      study were from the 2010 (baseline) and 2012 (follow-up) Hatoyama Cohort Study.
      Bonding social capital was assessed by individual perception of homogeneity of
      the neighborhood (the level of homogeneity among neighbors) and of networks (the
      amount of homogeneous personal networks) in relation to age, gender, and
      socioeconomic status. Bridging social capital was assessed by individual
      perception of heterogeneity of networks (the amount of heterogeneous personal
      networks) in relation to age, gender, and socioeconomic status. Odds ratios (ORs)
      and 95% confidence intervals (CIs) were calculated to evaluate the effects of
      baseline social capital on poor health outcome at follow-up by logistic
      regression analysis. In total, 681 people completed baseline and follow-up
      surveys. The mean age of participants was 71.8 +/- 5.1 years, and 57.9% were
      male. After adjusting for sociodemographics, lifestyle factors, comorbidity,
      functional capacity, baseline score of each outcome, and other bonding/bridging
      social capital, stronger perceived neighborhood homogeneity was inversely
      associated with poor self-rated health (OR = 0.55, 95% CI = 0.30-1.00) and
      depressive mood assessed by the Geriatric Depression Scale (OR = 0.58, 95% CI =
      0.34-0.99). When participants who reported a depressive mood at baseline were
      excluded, stronger perceived heterogeneous network was inversely associated with
      depressive mood (OR = 0.40, 95% CI = 0.19-0.87). Neither bonding nor bridging
      social capital was significantly associated with cognitive decline assessed by
      the Mini-Mental State Examination. In conclusion, bonding and bridging social
      capital affect health in different ways, but they both have beneficial effects on
      the health of older Japanese. Our findings suggest that intervention focusing on
      bonding and bridging social capital may improve various health outcomes in old
      age.

PMID- 24331906
TI  - Tobacco Road Finland - how did an accepted pleasure turn into an avoidable risk
      behaviour?
AB  - Smoking was once defined as an appropriate recreational substance or life
      comfort, but is now understood as a serious health risk and a public health
      problem important enough to be controlled by society. In this article the changed
      social position and development of tobacco regulations in Finland are studied
      from a perspective of social constructionism. The emergence of recent tobacco
      controls can be seen as a process whereby tobacco came to be defined as a social
      problem. I will argue that there were three primary definitions which played a
      decisive role in this process. Put in historical order, these three definitions
      contained (1) claims about harms to smokers, (2) claims about harms to others,
      and (3) claims about tobacco as a highly addictive drug. These conceptions
      together drove a complementary and mutually reinforcing re-conception of tobacco
      harms. Consequently, the emergence of these definitions led to the founding of
      new institutions, practices, and treatments. The leading value in the claim
      making process was public health, which transferred the state's interest away
      from fiscal revenues towards lowering the costs caused by tobacco diseases.
      Correspondingly, medical science and medical doctors gained a position as the
      leading authority in the defining the tobacco issue. The latest conceptual
      innovation is the idea of a tobacco-free Finland by 2040, representing a strategy
      of 'de-normalising' tobacco use. The reversal in the social and cultural position
      of tobacco, which in Finland went from one extreme to another, was not based on
      pressure created by any wider social movements or organised tobacco-specific
      citizens groups, as in some other countries, but rather by a state health
      administration supported by a relatively small network of tobacco control
      advocates. 

PMID- 24331907
TI  - Special issue introduction: Bioethics in the field.

PMID- 24331908
TI  - Simulation in cardiothoracic surgical training: where do we stand?
AB  - OBJECTIVES: Simulation may reduce the risks associated with the complex
      operations of cardiothoracic surgery and help create a more efficient, thorough,
      and uniform curriculum for cardiothoracic surgery fellowship. Here, we review the
      current status of simulation in cardiothoracic surgical training and provide an
      overview of all simulation models applicable to cardiothoracic surgery that have
      been published to date. METHODS: We completed a comprehensive search of all
      publications pertaining to simulation of cardiothoracic surgical procedures by
      using PubMed. RESULTS: Numerous cardiothoracic surgical simulators at various
      stages of development, assessment, and commercial manufacturing have been
      published to date. There is currently a predominance of models simulating
      coronary artery bypass grafting and bronchoscopy and a relative paucity of
      simulators of open pulmonary and esophageal procedures. Despite the wide range of
      simulators available, few models have been formally assessed for validity and
      educational value. CONCLUSIONS: Surgical simulation is becoming an increasingly
      important educational tool in training cardiothoracic surgeons. Our next steps
      forward will be to develop an objective, standardized way to assess surgical
      simulation training compared with the current apprenticeship model.

PMID- 24331910
TI  - Discussion.

PMID- 24331909
TI  - Parameters for successful nonoperative management of traumatic aortic injury.
AB  - OBJECTIVE: Blunt traumatic aortic injury is associated with significant
      mortality, and increased computed tomography use identifies injuries not
      previously detected. This study sought to define parameters identifying patients
      who can benefit from medical management. METHODS: We reviewed 4.5 years of blunt
      traumatic aortic injuries. Injury was classified as grade I (intimal flap or
      intramural hematoma), II (small pseudoaneurysm <50% circumference), III (large
      pseudoaneurysm >50% circumference), and IV (rupture/transection). Secondary signs
      of injury included pseudocoarctation, extensive mediastinal hematoma, and large
      left hemothorax. Follow-up, including computed tomography, was reviewed. RESULTS:
      We identified 97 patients: 31 grade I, 35 grade II, 24 grade III, and 7 grade IV;
      67(69%) male; mean age 47 +/- 18.8 years, mean Injury Severity Score 38.8 +/-
      14.6; overall survival 76 (78.4%). Secondary signs of injury were found in 30
      patients. Overall, 52 (53.6%) underwent repair, 45 undergoing thoracic
      endovascular aortic repair, with 2 (2.22%) procedure-related deaths, and 7
      undergoing open repair. Five patients undergoing thoracic endovascular aortic
      repair required 7 additional procedures. In 45 medically managed patients, there
      were 14 deaths (31%), all secondary to associated injuries. Injury Severity
      Scores of survivors and nonsurvivors were 33 +/- 10.8 and 48.6 +/- 12.8,
      respectively (P < .001). Follow-up showed resolution or no change in 21 (91%) and
      a small increase in 2 grade I injuries. CONCLUSIONS: All blunt traumatic aortic
      injury does not necessitate repair. Stratification by injury grade and secondary
      signs of injury identifies patients appropriate for medical management. Grade IV
      injury necessitates emergency procedures and carries high mortality. Grade III
      injury with secondary signs of injury should be urgently repaired; patients
      without secondary signs of injury may undergo delayed repair. Grade I and II
      injuries are amenable to medical management.

PMID- 24331911
TI  - Transaortic repair for the moderate functional mitral regurgitation.

PMID- 24331912
TI  - Sternal closure technique for bilateral transverse thoracosternotomy after
      bilateral sequential lung transplantation.

PMID- 24331913
TI  - Effect of preoperative renal function on long-term survival after cardiac
      surgery.

PMID- 24331914
TI  - Which patients will benefit more from off-pump coronary artery bypass grafting?

PMID- 24331915
TI  - B-type natriuretic peptide in children undergoing pediatric cardiac surgery: Just
      a marker of disease severity strongly related to age or much more?

PMID- 24331916
TI  - TAVI without surgical standby: is history repeating itself? A word of caution.

PMID- 24331917
TI  - Freestyle xenograft for aortic valve endocarditis.

PMID- 24331918
TI  - Reply to the editor.

PMID- 24331919
TI  - Inhibition of telomerase induces alternative lengthening of telomeres during
      human esophageal carcinogenesis.
AB  - Immortalization is an important step toward the malignant transformation of human
      cells and is critically dependent upon telomere maintenance. Two mechanisms are
      known to maintain human telomeres. The process of telomere maintenance is either
      mediated through activation of the enzyme telomerase or through an alternative
      mechanism of telomere lengthening called alternative lengthening of telomeres
      (ALT). Whereas 85% of all human tumors show reactivation of telomerase, the
      remaining 15% are able to maintain telomeres via ALT. Telomerase inhibitors are
      already investigated in clinical trials, although the regulation as well as
      potential coexistence and redundancy of both telomere maintenance mechanisms
      during distinct steps of carcinogenesis are poorly understood. Herein, we
      demonstrate that telomerase activity and ALT alternate in a cell cycle dependent
      fashion in human esophageal epithelial cells, and can coexist in a genetically
      defined model of oral-esophageal squamous carcinogenesis. Moreover, we show that
      immortalized premalignant cells as well as cancer cells are able to switch from
      telomerase activation to ALT upon inhibition of telomerase. This indicates that
      cancer cells treated with telomerase inhibitors can use alternative and adaptive
      ways to maintain their telomeres and thereby escape telomere-based therapeutic
      strategies. 

PMID- 24331920
TI  - [Factors associated with treatment adherence for tuberculosis infection].
AB  - OBJECTIVE: To analyze adherence to treatment of tuberculosis infection and to
      identify risk factors for its compliance. DESIGN: An observational historical
      cohort study. SETTING: Hospital Universitari Sant Joan d'Alacant (Alicante).
      PARTICIPANTS: All patients with a tuberculin skin test (TST) done during
      tuberculosis contact tracing during 6 years. RESULTS: We included 764
      tuberculosis contacts in the analysis. 59.7% of the 566 patients who completed
      the contact tracing, had tuberculosis infection (TI). Of the patients with TI,
      45.6% had not started treatment for tuberculosis infection (TTBI). Factors
      associated with not starting TTBI were: age (36-65 years, RR: 5.8; 95% CI: 1.2
      27.5, and > 65 years, RR: 11.3; 95% CI: 2.0-64.0), the social relationship with
      TB case (RR: 2.2; 95% CI 1.2-3.8), and the TST reaction (>= 15mm; RR: 0.5; 95%
      CI: 0.3-0.9). The completion rate for TTBI was 80.4% among people who started
      therapy. The treatment regimen was associated with greater compliance to TTBT (7
      9H, RR: 12.7; 95% CI: 1.5-107.3). CONCLUSIONS: The treatment compliance rate of
      Tuberculosis infection was high among people who started therapy. Almost a half
      of the contacts with TI did not start treatment, and associated factors were:
      age, social relationship, and the TST reaction. The treatment regimen was
      associated with greater compliance. It is important to know the factors
      associated with adherence to treatment of TI in each health area, and focus
      efforts on risk groups; thereby approaching the global control of tuberculosis.

PMID- 24331922
TI  - Preferences of inflammatory bowel disease patients for computerised versus face
      to-face psychological interventions.
AB  - BACKGROUND AND AIMS: Psychological interventions can be effective treatments for
      patients with medical illnesses such as inflammatory bowel disease (IBD).
      However, there are barriers to their widespread implementation such as lack of
      therapists, high costs, stigma, and poor accessibility in remote areas.
      Computerised psychological interventions can overcome these barriers. The aim of
      this study was to measure and compare the preferences of IBD patients for
      computerised versus face-to-face psychological interventions. METHODS: One
      hundred and two IBD patients were given a support willingness questionnaire which
      measured their willingness and confidence to participate in computerised and face
      to-face psychological interventions as well as the number of sessions they would
      be willing to participate in. RESULTS: IBD patients were more likely to want to
      take part in a computer based than face-to-face intervention (45.5% versus 16.8%,
      p=0.045). Furthermore, IBD patients were willing to participate in more sessions
      of computerised than face-to-face intervention median (5 vs. 3.5, Z=3.93,
      p<0.001). Younger females had a significantly higher acceptability of a
      computerised intervention than older females (chi(2)(1)=6.77, p=0.009) but the
      same was not found for males. Duration of disease was not associated with
      willingness to participate in an intervention. CONCLUSIONS: IBD patients appear
      more willing to participate in a computerised than face-to face psychological
      intervention. Future studies should attempt to study the effectiveness of
      computerised psychological interventions in IBD.

PMID- 24331921
TI  - Racial differences in risk of spontaneous abortions associated with
      periconceptional over-the-counter nonsteroidal anti-inflammatory drug exposure.
AB  - PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most common
      medications reported in pregnancy. NSAIDs directly impact prostaglandin pathways
      and have been proposed as potential risk factors for spontaneous abortions (SABs,
      gestation <20 weeks). SAB risk and drug response across several medications
      differ by race; therefore, we evaluated whether associations between NSAIDs and
      SAB risk differ by race. METHODS: Women were enrolled in the Right from the Start
      (2004-2010) prospective cohort. Data regarding over-the-counter NSAIDs up to the
      sixth week of pregnancy were obtained from interviews. Race was self-reported.
      Cox proportional hazards regression models were used to estimate the association
      between NSAID exposure and SAB, adjusted for confounders. RESULTS: Among 2493
      pregnancies, 12% were African American and 88% were Caucasian. NSAID exposure was
      reported by 40% (n = 124) of African Americans and 43% (n = 945) of Caucasians.
      Race-stratified analyses showed protection from SAB among African Americans
      (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.73-0.96) but
      no effect in Caucasians (aHR, 1.01; 95% CI 0.88-1.16). CONCLUSIONS: Our findings
      suggest that risk for SAB due to over-the-counter NSAIDs in early pregnancy is
      modified by race. Further investigation of dose, timing in gestation, and
      indication may help to further reconcile the relationship between race, NSAIDs,
      and SAB.

PMID- 24331923
TI  - A Nobel platform for new voices.

PMID- 24331924
TI  - Wnt and Bmp fit germ cells to a T.
AB  - Reporting in Developmental Cell, Aramaki et al. (2013) identify T as a key
      mediator of primordial germ cell (PGC) specification in the embryo.
      Deconstruction of how Bmp and Wnt signals regulate the expression and targeting
      of T to regulatory elements of either mesodermal or PGC genes has implications
      for differentiation in vitro.

PMID- 24331925
TI  - Hemogenic endothelial cell specification requires c-Kit, Notch signaling, and p27
      mediated cell-cycle control.
AB  - Delineating the mechanism or mechanisms that regulate the specification of
      hemogenic endothelial cells from primordial endothelium is critical for
      optimizing their derivation from human stem cells for clinical therapies. We
      previously determined that retinoic acid (RA) is required for hemogenic
      specification, as well as cell-cycle control, of endothelium during
      embryogenesis. Herein, we define the molecular signals downstream of RA that
      regulate hemogenic endothelial cell development and demonstrate that cell-cycle
      control is required for this process. We found that re-expression of c-Kit in RA
      deficient (Raldh2(-/-)) primordial endothelium induced Notch signaling and p27
      expression, which restored cell-cycle control and rescued hemogenic endothelial
      cell specification and function. Re-expression of p27 in RA-deficient and Notch
      inactivated primordial endothelial cells was sufficient to correct their defects
      in cell-cycle regulation and hemogenic endothelial cell development. Thus, RA
      regulation of hemogenic endothelial cell specification requires c-Kit, notch
      signaling, and p27-mediated cell-cycle control.

PMID- 24331926
TI  - A mesodermal factor, T, specifies mouse germ cell fate by directly activating
      germline determinants.
AB  - Germ cells ensure reproduction and heredity. In mice, primordial germ cells
      (PGCs), the precursors for spermatozoa and oocytes, are induced in pluripotent
      epiblast by BMP4 and WNT3, yet the underlying mechanism remains unclear. Here,
      using an in vitro PGC specification system, we show that WNT3 induces many
      transcription factors associated with mesoderm in epiblast-like cells through
      beta-CATENIN. Among these, T (BRACHYURY), a classical and conserved mesodermal
      factor, was essential for robust activation of Blimp1 and Prdm14, two of the
      germline determinants. T, but not SMAD1 or TCF1, binds distinct regulatory
      elements of both Blimp1 and Prdm14 and directly upregulates these genes,
      delineating the downstream PGC program. Without BMP4, a program induced by WNT3
      prevents T from activating Blimp1 and Prdm14, demonstrating a permissive role of
      BMP4 in PGC specification. These findings establish the key signaling mechanism
      for, and a fundamental role of a mesodermal factor in, mammalian PGC
      specification.

PMID- 24331927
TI  - FHOD1 is needed for directed forces and adhesion maturation during cell spreading
      and migration.
AB  - Matrix adhesions provide critical signals for cell growth or differentiation.
      They form through a number of distinct steps that follow integrin binding to
      matrix ligands. In an early step, integrins form clusters that support actin
      polymerization by an unknown mechanism. This raises the question of how actin
      polymerization occurs at the integrin clusters. We report here that a major
      formin in mouse fibroblasts, FHOD1, is recruited to integrin clusters, resulting
      in actin assembly. Using cell-spreading assays on lipid bilayers, solid
      substrates, and high-resolution force-sensing pillar arrays, we find that
      knockdown of FHOD1 impairs spreading, coordinated application of adhesive force,
      and adhesion maturation. Finally, we show that targeting of FHOD1 to the integrin
      sites depends on the direct interaction with Src family kinases and is upstream
      of the activation by Rho kinase. Thus, our findings provide insights into the
      mechanisms of cell migration with implications for development and disease. 

PMID- 24331929
TI  - CT imaging in congenital heart disease: an approach to imaging and interpreting
      complex lesions after surgical intervention for tetralogy of Fallot,
      transposition of the great arteries, and single ventricle heart disease.
AB  - Echocardiography and cardiac magnetic resonance imaging are the most commonly
      performed diagnostic studies in patients with congenital heart disease. A small
      percentage of patients with congenital heart disease will be referred to cardiac
      CT subsequent to echocardiography when magnetic resonance imaging is
      insufficient, contraindicated, or considered high risk. The most common complex
      lesions referred for CT at our institution are tetralogy of Fallot, transposition
      complexes, and single ventricle heart disease. This review discusses the most
      common surgical procedures performed in these patients and the technical
      considerations for optimal image acquisition on the basis of the prior procedure
      and the individual patient history. Cardiac CT can provide the functional and
      anatomic information required for decision making in complex congenital heart
      disease. Image interpretation is aided by knowledge of the common approaches to
      operative repair and the residual hemodynamic abnormalities. Acquisition and
      interpretation that is both individualized to the patient's underlying disease
      and the specific clinical question is likely to maintain diagnostic accuracy
      while decreasing the potential risk of cardiac CT. 

PMID- 24331928
TI  - Exo70 isoform switching upon epithelial-mesenchymal transition mediates cancer
      cell invasion.
AB  - Epithelial-mesenchymal transition (EMT) is an important developmental process
      hijacked by cancer cells for their dissemination. Here, we show that Exo70, a
      component of the exocyst complex, undergoes isoform switching mediated by ESRP1,
      a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial
      isoform of Exo70 affects the levels of key EMT transcriptional regulators such as
      Snail and ZEB2 and is sufficient to drive the transition to epithelial
      phenotypes. Differential Exo70 isoform expression in human tumors correlates with
      cancer progression, and increased expression of the epithelial isoform of Exo70
      inhibits tumor metastasis in mice. At the molecular level, the mesenchymal-but
      not the epithelial-isoform of Exo70 interacts with the Arp2/3 complex and
      stimulates actin polymerization for tumor invasion. Our findings provide a
      mechanism by which the exocyst function and actin dynamics are modulated for EMT
      and tumor invasion.

PMID- 24331930
TI  - Non-sedated, free breathing cardiac CT for evaluation of complex congenital heart
      disease in neonates.
AB  - BACKGROUND: Neonates with complex congenital heart disease (CHD) are at risk of
      adverse events from anesthesia. CT angiography (CTA) performed free breathing and
      without sedation has not been reported for evaluation of complex CHD in neonates.
      OBJECTIVES: The aim was to evaluate the image quality and risk of free breathing,
      non-sedated cardiac CTA for definition of CHD in the neonatal period and to
      determine accuracy compared with interventional findings. METHODS: This is a
      combined retrospective-prospective single institution review of all non-sedated,
      free breathing cardiac CT angiograms performed in patients <1 month of age with
      complex CHD. Diagnosis, scan acquisition parameters, image quality (1- to 4-point
      scale), adverse events, radiation dose estimates, and accuracy compared with
      operative and interventional catheterization findings were recorded. Results are
      reported as median and interquartile range. RESULTS: Nineteen non-sedated, free
      breathing, neonatal cardiac CT angiograms were performed during the time of
      review. All studies were diagnostic with a mean image quality score of 1.1 +/-
      0.3. Median total procedural dose-length product was 11 (range, 10-14), CT dose
      index volume was 0.47 (range, 0.31-0.5). Median unadjusted radiation dose was
      0.15 mSv (range, 0.14-0.2 mSv), age- and size-adjusted radiation dose was 0.86
      mSv (range, 0.78-1.1 mSv). No adverse events and no discrepancies compared with
      surgical or catheterization findings were found in the 17 of 19 patients that had
      subsequent intervention. CONCLUSIONS: Cardiac CTA can be performed in the
      neonatal period free breathing and without sedation. Image quality is excellent,
      and there is high accuracy compared with surgical and catheterization findings at
      the time of intervention.

PMID- 24331931
TI  - Cardiovascular imaging trends in congenital heart disease: a single center
      experience.
AB  - BACKGROUND: Cardiac magnetic resonance imaging (MRI) and CT are available in the
      recent era at many pediatric cardiac centers. OBJECTIVE: The aim was to provide a
      contemporary description of diagnostic imaging trends for definition of
      congenital heart disease (CHD). METHODS: Echocardiography, cardiac
      catheterization, cardiac MRI, and cardiac CT use in patients with congenital
      heart disease at a single institution was retrospectively recorded (2005-2012).
      Surgical procedures were recorded. Total and modality-specific rates were
      estimated by Poisson regression and compared. The median age, studies in patients
      aged >17 years, and referral diagnosis were tabulated for the last year of
      review. RESULTS: An average of 11,940 cardiovascular diagnostic tests was
      performed annually. The number of total studies, echocardiograms,
      catheterizations, and surgical procedures, did not change significantly across
      time. Echocardiography comprised 95% to 97% of all studies performed during each
      year of review. The use of cardiac MRI (2%) and cardiac CT (1%) increased
      linearly (P < .001), and the use of diagnostic catheterization decreased (0.7%; P
      = .0005). The median age was 3 years for echocardiography, 15 years for MRI, 11
      years for CT, and 3 years for catheterization. The percentage of patients aged
      >17 years was 9% for echocardiography, 33% for cardiac MRI, 29% for cardiac CT,
      and 8% for catheterization. Most patients undergoing CT, MRI, and diagnostic
      catheterization had moderate or complex CHD. CONCLUSION: Cardiac CT is used
      increasingly in the recent era for evaluation of CHD. The increased use of both
      cardiac CT and cardiac MRI are temporally associated with a decrease in
      diagnostic cardiac catheterization.

PMID- 24331932
TI  - Diagnostic accuracy of CT angiography in infants with tetralogy of Fallot with
      pulmonary atresia and major aortopulmonary collateral arteries.
AB  - BACKGROUND: CT angiography (CTA) is increasingly used for the evaluation of
      congenital heart disease. OBJECTIVE: The aim was to determine the diagnostic
      accuracy of CTA in infants with tetralogy of Fallot with pulmonary atresia (ToF
      PA) and major aortopulmonary collateral arteries (MAPCAs). METHODS: We
      retrospectively evaluated 18 consecutive patients (7 girls; median age, 6 days;
      range, 1-334 days) with ToF-PA and MAPCAs. Findings on CTA were compared with
      diagnostic catheterization (n = 16) or intraoperative findings (n = 2) for the
      number of MAPCAs, their diameter, origin, and supplied lung lobes and for the
      presence and diameter of central pulmonary arteries. Spearman correlation
      coefficient was calculated to assess the correlation between diameter
      measurements on CTA and catheterization. CTA dose-length product and
      catheterization dose-area product were recorded, and effective radiation doses
      were calculated with the use of age-specific conversion factors. RESULTS:
      Agreement was found between CTA and catheterization or intraoperative findings
      for the number of MAPCAs, their origin, and supplied lung lobes in all cases. In
      11 of 13 patients, CTA accurately demonstrated central pulmonary arteries. A good
      correlation was found between diameter measurements on CTA and catheterization
      for MAPCAs (r = 0.83) and central pulmonary arteries (r = 0.82). Median effective
      doses were 0.9 mSv for CTA and 14.4 mSv for catheterization (P < .001).
      CONCLUSION: CTA is accurate in the preoperative evaluation of infants with ToF-PA
      and MAPCAs and is associated with a substantially lower radiation dose than
      catheterization. Preoperative diagnostic catheterization, therefore, may only be
      necessary in select patients with small MAPCAs in whom the precise assessment of
      central pulmonary arteries is required for surgical planning.

PMID- 24331933
TI  - Image quality of ultra-low-dose dual-source CT angiography using high-pitch
      spiral acquisition and iterative reconstruction in young children with congenital
      heart disease.
AB  - BACKGROUND: Obtaining diagnostic CT image quality with ultra-low radiation dose
      in young children with congenital heart disease remains challenging. OBJECTIVE:
      We evaluated the feasibility and image quality of prospectively electrocardiogram
      (ECG)-triggered high-pitch spiral acquisition with iterative reconstruction for
      pediatric cardiovascular CT angiography. METHODS: Sixty-two consecutive pediatric
      patients younger than 2 years with congenital heart disease underwent
      prospectively ECG-triggered high-pitch spiral dual-source CT acquisition.
      Patients were randomly assigned into 2 groups: full tube current (40-70 mAs)
      scans with filtered back projection reconstruction (group A) and half tube
      current (20-35 mAs) scans with sinogram-affirmed iterative reconstruction (group
      B). Attenuation, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio
      (CNR), and subjective image quality were compared between the 2 groups. Effective
      radiation dose was also estimated for both groups. RESULTS: No significant
      difference was found in the attenuation, image noise, SNR, and CNR between the 2
      groups in the same evaluated anatomic regions, whereas the attenuation and image
      noise were slightly lower, and the SNR and CNR were slightly higher in group B.
      No significant difference was found in subjective image quality between the 2
      groups (4.27 +/- 0.73 vs. 4.34 +/- 0.42; P = .813). Effective dose was 0.06 +/-
      0.03 mSv in group B and 0.13 +/- 0.04 mSv in group A, reflecting dose savings of
      53.8% by using iterative reconstruction. CONCLUSIONS: A combination of
      prospectively ECG-triggered high-pitch spiral acquisition, low tube current, and
      iterative reconstruction may offer diagnostic image quality in pediatric
      cardiovascular CT angiography with effective radiation dose < 0.1 mSv.

PMID- 24331935
TI  - Single coronary artery: spectrum of imaging findings with multidetector CT.
AB  - Single coronary artery is a rare congenital anomaly in which a single artery
      arises from the aorta. The anomalous single trunk supplies blood to the entire
      heart. It is classified according to its origin, branching pattern, and course.
      The presence of a single coronary artery can be an isolated finding or associated
      with additional cardiac anomalies. Diagnosis is important because of therapeutic
      implications, although it is an incidental finding. As with any other coronary
      anomalies, its recognition is more common today because of increasing use of
      multidetector CT. The objective of this article is to review the classification
      of single coronary artery anomaly and its clinical significance and to illustrate
      the imaging findings on multidetector CT. 

PMID- 24331934
TI  - Congenital anomalies of coronary arteries in complex congenital heart disease:
      diagnosis and analysis with dual-source CT.
AB  - BACKGROUND: Congenital heart diseases (CHDs) are sometimes associated with
      coronary artery anomalies (CAAs). Accurate preoperative evaluation of coronary
      artery anatomy is essential for successful surgical repair of complex CHD.
      OBJECTIVE: The aim of this study was to evaluate the incidence of congenital CAAs
      in patients with complex CHD at dual-source CT. METHODS: Four hundred seventeen
      consecutive patients with complex CHD underwent contrast-enhanced cardiac CT
      angiography. The results were retrospectively analyzed, including the types and
      incidences of CAAs in various forms of complex CHD. Each patient was analyzed
      independently by 2 experienced cardiovascular radiologists. Image quality of
      coronary arteries was assessed on a 5-point scale with 2 or less being
      nondiagnostic. RESULTS: Thirty-five of 417 studies were nondiagnostic (8.39%).
      Sixty-three cases of CAA (15.11%) were detected by anomalous ostia and coronary
      arteries. CAA was involved in 6 of 108 patients with tetralogy of Fallot (5.56%),
      18 of 84 patients with double outlet right ventricle (21.43%), 11 of 97 patients
      with pulmonary artery atresia (11.34%), 7 of 36 patients with transposition of
      the great arteries (22.22%), 15 of 41 patients with single ventricle (36.59%), 4
      of 12 patients with truncus arteriosus/aortopulmonary window (33.33%), and 2 of
      39 patients with interruption of the aortic arch/coarctation of the aorta
      (5.13%). Twenty of these were accompanied with an anomalous coronary course
      (31.74%). CONCLUSION: Patients with complex CHD have a higher prevalence of CAAs,
      which should be considered before surgery. Dual-source CT is an effective
      technique to visualize and evaluate complex CHD.

PMID- 24331936
TI  - Cardiovascular manifestations of Williams syndrome: imaging findings.
AB  - Williams syndrome is a relatively common (1 in 10,000 live births) genetic
      disorder caused by a deletion involving chromosome 7 that results in a variety of
      clinically significant abnormalities, including developmental delay, behavioral
      changes, hypercalcemia, and a distinct "elfin" facial appearance. Congenital
      cardiovascular disease that presents in childhood is responsible for most of the
      morbidity and mortality associated with this disorder. The purpose of this
      pictorial essay is to review imaging findings of some of the more common
      cardiovascular manifestations of Williams syndrome and to highlight some of the
      unique anatomic variations that can be seen in these patients. 

PMID- 24331938
TI  - Dilated coronary arterial obstruction due to coronary artery microfistulae.
AB  - An 80-year-old asymptomatic man presented with ST-segment elevation in leads V1
      to V5. Coronary CT angiography showed that microfistulae arising from multiple
      arteries may have led to myocardial infarction from intracoronary thromboembolism
      within the dilated left anterior descending (LAD). 

PMID- 24331937
TI  - Cardiovascular manifestations of heterotaxy and related situs abnormalities
      assessed with CT angiography.
AB  - Heterotaxy and situs abnormalities describe an abnormal arrangement of visceral
      organs in the thoracoabdominal cavity across the normal left-right axis of the
      body. It is associated with a high occurrence of congenital heart and abdominal
      defects, including anomalous pulmonary venous connections, systemic venous
      abnormalities, asplenia, and intestinal malrotation. Without proper diagnosis and
      surgical intervention, the prognosis of patients with heterotaxy syndrome and
      associated congenital defects is extremely poor. Complex intracardiac and
      extracardiac lesions are common in heterotaxy and can be difficult to assess by
      echocardiography. CT angiography (CTA) is a useful tool in this setting to
      accurately assess intracardiac and extracardiac abnormalities in this population
      for medical or surgical management. The intention of this pictorial essay is to
      review the most common cardiovascular defects involved with heterotaxy syndrome
      in addition to emphasizing the utility of CTA in the identification and
      classification of anomalies seen in these patients. This review briefly defines
      most common terminology used in situs abnormalities as well as presents CT images
      and 3-dimensional reconstructions of common anomalies associated with situs
      abnormalities. In summary, this review should prepare radiologists and pediatric
      cardiologists to describe heterotaxy and situs abnormalities in addition to
      recognizing the utility of CTA in these patients. 

PMID- 24331939
TI  - Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion
      injury in the rat kidney.
AB  - BACKGROUND: To investigate the protective effect of 2-aminoethyl diphenylborinate
      (2-APB) against ischemia-reperfusion (I/R) injury in the rat kidney by an
      experimental study. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were
      randomly divided into the following three groups: (1) sham group, (2) I/R group,
      and (3) I/R + 2-APB group. Renal I/R injury was induced by clamping the left
      renal pedicle for 45 min after right nephrectomy, followed by 3 h of reperfusion.
      The therapeutic agent 2-APB was administered intravenously at a dose of 2 mg/kg
      10 min before renal ischemia. Glutathione, superoxide dismutase, total
      antioxidant capacity, malondialdehyde, tumor necrosis factor alpha, interleukin
      6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels
      were measured from blood samples, and the rats were sacrificed subsequently.
      Tissue samples were scored histopathologically. Visualization of apoptotic cells
      was performed using the terminal deoxynucleotidyl transferase dUTP nick end
      labeling staining method. RESULTS: 2-APB significantly reduced serum
      malondialdehyde, tumor necrosis factor alpha, interleukin 6, aspartate
      aminotransferase, alanine aminotransferase, and creatinine levels in the I/R
      injury group. However, glutathione, superoxide dismutase, and total antioxidant
      capacity levels increased significantly. Histopathologic scores were
      significantly better and the rate of apoptosis was lower in the 2-APB group.
      CONCLUSIONS: 2-APB reduces oxidative stress and damage caused by renal I/R
      injury. The results of this study demonstrate that 2-APB can be used as an
      effective agent against I/R injury in the kidney.

PMID- 24331940
TI  - Isotetrandrine protects against lipopolysaccharide-induced acute lung injury by
      suppression of mitogen-activated protein kinase and nuclear factor-kappa B.
AB  - BACKGROUND: Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B
      (NF-kappaB) signaling pathways are pleiotropic regulator of many genes involved
      in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study
      aimed to reveal the protective effect of isotetrandrine (ITD), a small molecule
      inhibitor, on various aspects of LPS-induced inflammation in vitro and in vivo.
      METHODS: In vitro, RAW 264.7 cells were pretreated with different dose of ITD 1 h
      before treatment with 1 mg/L of LPS. In vivo, to induce ALI, male BALB/c mice
      were injected intranasally with LPS and treated with ITD (20 and 40 mg/kg) 1 h
      before LPS. RESULTS: In vitro, the cytokine levels of tumor necrosis factor
      alpha, interleukin (IL)-1beta, and IL-6 in supernatant were reduced by ITD.
      Meanwhile, in vivo, pulmonary inflammatory cell infiltration, myeloperoxidase
      activity, total cells, neutrophils, macrophages, along with the levels of tumor
      necrosis factor-alpha, IL-1beta, and IL-6 in bronchoalveolar lavage fluid were
      dose-dependently attenuated by ITD. Furthermore, our data showed that ITD
      significantly inhibited the activation of MAPK and NF-kappaB, which are induced
      by LPS in ALI model. CONCLUSIONS: These results suggested that ITD dose
      dependently suppressed the severity of LPS-induced ALI by inactivation of MAPK
      and NF-kappaB, which may involve the inhibition of tissue oxidative injury and
      pulmonary inflammatory process.

PMID- 24331941
TI  - CD16 inhibition increases host survival in a murine model of severe sepsis.
AB  - BACKGROUND: To investigate the therapeutic effect of monoclonal antibody (mAb)
      induced CD16 (FcgammaRIII) inhibition in a murine model of high-grade (severe)
      sepsis. MATERIALS AND METHODS: In a prospective controlled animal study, 2 MUg of
      CD16/32 (FcgammaRIII/FcgammaRII) or the same volume of normal saline was
      administered intraperitoneally to BALB/c FcgammaRII(-/-) mice at the time of
      cecal ligation and puncture (CLP) in a murine model of high-grade sepsis.
      Subcutaneous administration of CD16/32 (0.5 MUg/24 h) or normal saline continued
      for 7 d. Survival was evaluated, and the underlying therapeutic mechanism of mAb
      induced CD16 inhibition was investigated. RESULTS: CD16 expression was
      significantly increased on peripheral blood CD14(+) monocytes from mice with high
      grade sepsis compared with non-septic control mice (1579.40 +/- 217.75 versus
      461.10 +/- 36.13; P < 0.05). CD16/32 mAb treatment increased the survival of mice
      with high-grade sepsis (P < 0.05) and significantly decreased their elevated
      levels of serum tumor necrosis factor alpha (36.70 +/- 9.97 versus 52.60 +/-
      10.69; P < 0.05) and interleukin 1beta (1149.40 +/- 244.09 versus 2605.60 +/-
      353.74; P < 0.05) at 6 and 24 h after CLP, respectively. Moreover, CD16/32 mAb
      treated mice with high-grade sepsis had fewer bacteria in their blood and
      peritoneal lavage than mice just treated with normal saline at 24 h after CLP (P
      < 0.05). CONCLUSIONS: CD16/32 mAb-induced CD16 inhibition increased the survival
      of mice with high-grade sepsis, which may have been because of the concomitant
      suppression of tumor necrosis factor alpha and interleukin 1beta as well as the
      enhancement of monocyte phagocytosis. Thus, targeted inhibition of CD16 can
      potentially improve the outcome of selected patients with severe sepsis.

PMID- 24331942
TI  - Journal of Critical Care: 2014.

PMID- 24331943
TI  - Loop diuretic strategies in patients with acute decompensated heart failure: a
      meta-analysis of randomized controlled trials.
AB  - PURPOSE: The safety and efficacy of continuous infusion vs bolus injection of
      intravenous loop diuretics to treat acute decompensated heart failure were
      debated. Our aim is to compare the administration routes of diuretics in
      hospitalized patients with acute decompensated heart failure. METHODS: A
      systematic review and meta-analysis of randomized controlled trials was performed
      to evaluate the effects of continuous infusion vs bolus administration of loop
      diuretics in patients with acute decompensated heart failure. The primary end
      points were urine outputs, body weight loss, all causes of mortality, and death
      from cardiovascular causes. Secondary end points were electrolyte imbalance,
      change in creatinine levels, tinnitus or hearing loss, and days of
      hospitalization. RESULTS: Ten randomized controlled trials with 518 patients were
      identified. Continuous infusion of diuretics was associated with a significantly
      greater weight loss (weighted mean difference, 0.78; 95% confidence interval,
      0.03-1.54) compared with bolus injection. Urine output, the incidence of
      electrolyte imbalance, change in creatinine level, length of hospitalization, the
      incidence of ototoxicity, cardiac mortality, and all-cause mortality showed no
      significant differences between the 2 groups. CONCLUSION: Meta-analysis of the
      existing limited studies did not confirm any significant differences in the
      safety and efficacy with continuous administration of loop diuretic, compared
      with bolus injection in patients with acute decompensated heart failure.

PMID- 24331944
TI  - Thrombin generation and fibrin clot formation under hypothermic conditions: an in
      vitro evaluation of tissue factor initiated whole blood coagulation.
AB  - BACKGROUND: Despite trauma-induced hypothermic coagulopathy being familiar in the
      clinical setting, empirical experimentation concerning this phenomenon is
      lacking. In this study, we investigated the effects of hypothermia on thrombin
      generation, clot formation, and global hemostatic functions in an in vitro
      environment using a whole blood model and thromboelastography, which can
      recapitulate hypothermia. METHODS: Blood was collected from healthy individuals
      through venipuncture and treated with corn trypsin inhibitor, to block the
      contact pathway. Coagulation was initiated with 5pM tissue factor at temperatures
      37 degrees C, 32 degrees C, and 27 degrees C. Reactions were quenched over time,
      with soluble and insoluble components analyzed for thrombin generation,
      fibrinogen consumption, factor (f)XIII activation, and fibrin deposition. Global
      coagulation potential was evaluated through thromboelastography. RESULTS: Data
      showed that thrombin generation in samples at 37 degrees C and 32 degrees C had
      comparable rates, whereas 27 degrees C had a much lower rate (39.2 +/- 1.1 and 43
      +/- 2.4 nM/min vs 28.6 +/- 4.4 nM/min, respectively). Fibrinogen consumption and
      fXIII activation were highest at 37 degrees C, followed by 32 degrees C and 27
      degrees C. Fibrin formation as seen through clot weights also followed this
      trend. Thromboelastography data showed that clot formation was fastest in samples
      at 37 degrees C and lowest at 27 degrees C. Maximum clot strength was similar for
      each temperature. Also, percent lysis of clots was highest at 37 degrees C
      followed by 32 degrees C and then 27 degrees C. CONCLUSIONS: Induced hypothermic
      conditions directly affect the rate of thrombin generation and clot formation,
      whereas global clot stability remains intact.

PMID- 24331945
TI  - Effect of type II diabetes mellitus on outcomes in patients with acute
      respiratory distress syndrome.
AB  - PURPOSE: The acute respiratory distress syndrome (ARDS) is a life-threatening
      condition, whereas the presence of diabetes has been shown to be protective in
      its development. We undertook this study to assess the association of type II
      diabetes mellitus with clinical outcomes in patients with ARDS. MATERIALS AND
      METHODS: We retrospectively examined the medical records of consecutive series of
      patients with ARDS requiring mechanical ventilation from January 2008 to March
      2011. Patients with type I diabetes were excluded from the study. Clinical
      outcomes such as ventilator-free days, mortality, length of stay in the hospital
      and intensive care unit (ICU), and reintubations were compared based on the
      presence of diabetes. Multivariate regression model was used to find if the
      presence of type II diabetes mellitus predicts ventilator-free days at day 28.
      RESULTS: Two hundred forty-nine patients with ARDS were admitted to the ICU
      during the study period. Fifty (20%) subjects had type II diabetes mellitus.
      Differences in ventilator-free days, in-hospital mortality, reintubation rate,
      and length of stay in the hospital or ICU were not statistically significant
      between diabetic and nondiabetic patients with ARDS. Acute Physiologic and
      Chronic Health Evaluation II, ICU specialty, use of vasopressors, and the need
      for reintubation were predictors of ventilator-free days at day 28. The presence
      of type II diabetes mellitus and its adjustment by body mass index did not show
      association with ventilator-free days at day 28. CONCLUSIONS: The presence of
      type II diabetes mellitus is not associated with clinical outcomes in ARDS, even
      when its presence is adjusted by body mass index.

PMID- 24331946
TI  - Intensive care specialists' knowledge, attitudes, and professional use of
      published research evidence: a mail-out questionnaire survey of appropriate use
      of research evidence in clinical practice.
AB  - PURPOSE: This survey investigates the knowledge, attitudes, and use of published
      research in clinical practice by intensive care specialists. MATERIALS AND
      METHODS: A mail-out questionnaire was sent to randomly selected intensive care
      specialists registered with the Australian and New Zealand College of Intensive
      Care Medicine. RESULTS: The response rate was 55.9% (133/238). The average score
      for research knowledge was 2.9 of 6. Eighty-five (65.4%) of 130 respondents
      reported positive feelings toward using published research evidence in clinical
      practice, with 96.6% (126/130) reporting use of the concepts of evidence-based
      medicine at least sometimes. Randomized trials were rated as the most frequently
      read evidence (rank score, 3.7 of 5), with "Information obtained from the
      Cochrane Library" the least frequently read (rank score, 2.8 of 5). The most
      inhibiting barrier to use of published research evidence in practice was "a lack
      of good evidence providing meaningful answers to clinical problems" (rank score,
      3.5 of 5). Eighty-eight (67.7%) of 130 respondents appropriately used published
      research evidence in clinical practice. CONCLUSIONS: Respondents reported
      generally positive attitudes toward using published research evidence, in
      clinical practice; however, room for improvement in technical knowledge relating
      to published research evidence was noted.

PMID- 24331947
TI  - Ventilator settings and monitoring parameter targets for initiation of continuous
      mandatory ventilation: a questionnaire study.
AB  - PURPOSE: To inform development of educational tools, we sought to identify
      initial ventilator settings and monitoring targets for 3 scenarios. METHOD: A
      survey was e-mailed to Canadian Society of Respiratory Therapists members with 2
      reminders in March/April 2011. RESULTS: Total evaluable surveys were 363. More
      participants selected pressure as opposed to volume ventilation for acute
      respiratory distress syndrome (ARDS; 77%) than for chronic obstructive pulmonary
      disease (COPD; 50%) and postoperative ventilation (32%; P < .001). Mean tidal
      volume was lower for ARDS than for COPD and postoperative ventilation (5.7, 6.9,
      and 7.2 mL/kg, respectively; P < .001). Maximum acceptable plateau pressures were
      highest for ARDS (30 cm H2O vs 29 cm H2O [COPD] and 27 cm H2O [postoperative], P
      < .001). Initial positive expiratory end pressure (12 cm H2O vs 7 cm H2O vs 5 cm
      H2O) and fraction of inspired oxygen (Fio2; 1.0 vs 0.5 vs 0.3) were also higher
      for ARDS (both P < .001); however, only 8% selected a positive expiratory end
      pressure/Fio2 combination as recommended by ARDSnet. Values of oxygen saturation
      as measured by pulse oximetry of 97% (ARDS) and 94% (COPD and postoperative) were
      considered appropriate for Fio2 reduction. The lowest pH was 7.28 vs 7.23 vs
      7.26; the highest pH was 7.46 vs 7.44 vs 7.46 (P < .001). Partial pressure of
      carbon dioxide (arterial) of 51 mm Hg (postoperative) to 65 mm Hg (ARDS) was
      considered acceptable. CONCLUSION: Lung protective ventilation was favored, yet
      distinct differences in ventilator settings were evident. Monitoring targets
      suggested relatively conservative practices for Fio2 reduction but an
      understanding of permissive hypercapnia.

PMID- 24331949
TI  - G-glutamyl transferase: a novel prognostic marker for cardiovascular disease.

PMID- 24331948
TI  - Are written advance directives helpful to guide end-of-life therapy in the
      intensive care unit? A retrospective matched-cohort study.
AB  - PURPOSE: The purpose of the study was to determine whether treatment preferences
      in patients' advance directives (ADs) are associated with life-supporting
      treatments received during end-of-life care in the intensive care unit (ICU).
      MATERIAL AND METHODS: This is a retrospective cohort study, including patients
      who died in 4 ICUs of a university hospital in Germany. Patients with ADs were
      matched with 2 patients each without ADs using propensity scores. RESULTS: Sixty
      four (13%) of 477 patients had ADs, written a median of 109 weeks before
      admission. Five categories of applicability conditions were identified, most of
      them difficult to interpret in the ICU (eg, "advanced brain impairment" or
      "imminent death"). Advance directives contained a number of treatment refusals.
      Specifically, 63 of 64 refused "life-sustaining measures." Compared to patients
      without ADs, patients with ADs were less likely to receive cardiopulmonary
      resuscitation (9% vs 23%, P = .029) and more likely to have do-not-resuscitate
      orders (77% vs 56%, P = .007). Therapy-limiting decisions and ICU length of stay
      did not differ between those with or without ADs. CONCLUSIONS: Patients with ADs
      are less likely to receive cardiopulmonary resuscitation but otherwise receive
      similar life-sustaining treatments compared to matched patients without ADs. More
      research is needed to explore reasons for potential noncompliance with patient
      preferences.

PMID- 24331950
TI  - Is Takotsubo syndrome a frequent encounter in the respiratory intensive care
      unit?

PMID- 24331952
TI  - The outcome of cancer patients with acute respiratory distress syndrome.
AB  - OBJECTIVE: The objective of the study is to determine the 28-day mortality of
      critically ill cancer patients with acute respiratory distress syndrome (ARDS).
      DESIGN: This is a retrospective cohort study of patients enrolled in the ARDS
      Network randomized controlled trials. RESULTS: A total of 2515 patients did not
      have cancer, and 116 patients had cancer. Patients with cancer were older
      (median, 61 vs 49 years; P < .0001), more critically ill (the median Acute
      Physiology and Chronic Health Evaluation III score without cancer comorbidity was
      105 for the cancer group compared with 87 for those without cancer; P < 0.0001),
      and more likely to have pneumonia or sepsis as cause of acute lung injury (79.31%
      vs 62.70%; P = .0011). The overall mortality at day 28 was 25.7%. Patients with
      cancer had significantly higher mortality (55.2%) compared with those without
      cancer (24.3%) (P < .0001). The odds ratio for mortality from ARDS at 28 days for
      cancer patients was 2.54 (95% confidence interval [CI], 1.570-4.120). Acute
      Physiology and Chronic Health Evaluation III score and age were found to be
      significant predictors of outcome in cancer patients with odds ratio of 1.034
      (95% CI, 1.007-1.062; P = .0135) and 1.075 (95% CI, 1.024-1.129, P = .0036),
      respectively. CONCLUSIONS: Cancer patients with ARDS have a significantly higher
      risk of death compared with those without cancer. The increased risk appeared to
      be mediated by increased severity of illness at presentation, as well as by age.

PMID- 24331953
TI  - Multimer monitoring of CMV-specific T cells in research and in clinical
      applications.
AB  - Multimer monitoring has become a standard technique for detection of antigen
      specific T cells. The term "multimer" refers to a group of reagents based on the
      multimerisation of molecules in order to raise avidity and thus stabilize binding
      to their ligand. Multimers for detection of antigen-specific T-cell responses are
      based on major histocompatibility complex class I peptide complexes. Multimer
      staining enables fast and direct visualization of antigen-specific T cells; thus,
      it is widely applied to assess antiviral immunity, e.g., monitor patients in
      vaccination trials or confirm purity of cell products for adoptive transfer.
      Assessment of T-cell immunity against persistent pathogens like cytomegalovirus
      (CMV) is of major importance in immunosuppressed patients. Recent advancements of
      multimers facilitate reversible labeling and allow isolation of epitope-specific
      T cells for adoptive transfer. Here, we give an overview on the different
      multimers and their applications, with an emphasis on CMV-specific T-cell
      responses. 

PMID- 24331954
TI  - The chronostratigraphy of the Haua Fteah cave (Cyrenaica, northeast Libya).
AB  - The 1950s excavations by Charles McBurney in the Haua Fteah, a large karstic cave
      on the coast of northeast Libya, revealed a deep sequence of human occupation.
      Most subsequent research on North African prehistory refers to his discoveries
      and interpretations, but the chronology of its archaeological and geological
      sequences has been based on very early age determinations. This paper reports on
      the initial results of a comprehensive multi-method dating program undertaken as
      part of new work at the site, involving radiocarbon dating of charcoal, land
      snails and marine shell, cryptotephra investigations, optically stimulated
      luminescence (OSL) dating of sediments, and electron spin resonance (ESR) dating
      of tooth enamel. The dating samples were collected from the newly exposed and
      cleaned faces of the upper 7.5 m of the ~14.0 m-deep McBurney trench, which
      contain six of the seven major cultural phases that he identified. Despite
      problems of sediment transport and reworking, using a Bayesian statistical model
      the new dating program establishes a robust framework for the five major
      lithostratigraphic units identified in the stratigraphic succession, and for the
      major cultural units. The age of two anatomically modern human mandibles found by
      McBurney in Layer XXXIII near the base of his Levalloiso-Mousterian phase can now
      be estimated to between 73 and 65 ka (thousands of years ago) at the 95.4%
      confidence level, within Marine Isotope Stage (MIS) 4. McBurney's Layer XXV,
      associated with Upper Palaeolithic Dabban blade industries, has a clear
      stratigraphic relationship with Campanian Ignimbrite tephra. Microlithic Oranian
      technologies developed following the climax of the Last Glacial Maximum and the
      more microlithic Capsian in the Younger Dryas. Neolithic pottery and perhaps
      domestic livestock were used in the cave from the mid Holocene but there is no
      certain evidence for plant cultivation until the Graeco-Roman period. 

PMID- 24331956
TI  - Reply to letter.

PMID- 24331957
TI  - When is a completion axillary lymph node dissection necessary in the presence of
      a positive sentinel lymph node?
AB  - BACKGROUND: The management of the axilla in the presence of positive sentinel
      lymph node (SLN) remains controversial. Many centres forgo completion axillary
      lymph node dissection (cALND) in the presence of micrometastatic disease. The
      American College of Surgeons Oncology Group (ACOSOG) Z0011 trialists argue for
      extending this to macrometastasis. The aim of this study was to correlate tumour
      burden in SLNs with that in the residual lymph node basin to determine the
      likelihood of residual disease in patients with micro- and macrometastasis in the
      SLN. METHODS: Patients who underwent cALND following a positive SLN were analysed
      for histopathological features of the primary tumour and burden of axillary
      disease. RESULTS: Of 155 patients, 115 (74%) had macrometastases and 40 (26%)
      micrometastases in the SLNs. Residual axillary disease was detected in 55/155
      (35%) patients with macrometastases and 4/40 (10%) with micrometastases.
      Generally, with increasing size of metastasis in the SLN there was an increasing
      risk of further disease in residual lymph nodes. Logistic regression analysis
      showed increased odds ratios for further disease for all groups when compared
      with the <2mm (micrometastasis) SLN group. CONCLUSION: Patients may be advised to
      forgo cALND where the SLN contains isolated tumour cells or micrometastasis.
      Recommendations for proceeding to cALND can be based on the size of metastasis in
      the SLN, which relates to the risk of further disease in the residual axillary
      lymph nodes and subsequent regional recurrence.

PMID- 24331955
TI  - Modeling heterogeneous patients with a clinical diagnosis of schizophrenia with
      induced pluripotent stem cells.
AB  - Schizophrenia (SZ) is a devastating complex genetic mental condition that is
      heterogeneous in terms of clinical etiologies, symptoms, and outcomes. Despite
      decades of postmortem, neuroimaging, pharmacological, and genetic studies of
      patients, in addition to animal models, much of the biological mechanisms that
      underlie the pathology of SZ remain unknown. The ability to reprogram adult
      somatic cells into human induced pluripotent stem cells (hiPSCs) provides a new
      tool that supplies live human neurons for modeling complex genetic conditions
      such as SZ. The purpose of this review is to discuss the technical and clinical
      constraints currently limiting hiPSC-based studies. We posit that reducing the
      clinical heterogeneity of hiPSC-based studies, by selecting subjects with common
      clinical manifestations or rare genetic variants, will help our ability to draw
      meaningful insights from the necessarily small patient cohorts that can be
      studied at this time. 

PMID- 24331958
TI  - [Trend in dietary calcium intake among Chinese children and adolescents aged 4 to
      17 years in nine provinces from 1991 to 2009].
AB  - OBJECTIVE: To understand the daily calcium intake, food sources and the trends
      among Chinese children and adolescents aged 4 to 17 years from 1991 to 2009.
      METHODS: Consecutive 3-day-24-hour dietary recall data from the seven waves of
      the China Health and Nutrition Survey(CHNS)was used to describe the status and
      trends of daily calcium intake and related food sources. RESULTS: Between 1991
      and 2009, the daily intake of calcium in Chinese children and adolescents showed
      an increasing trend. In 2009, the average intakes of calcium in Chinese boys and
      girls were 311.2 mg/d and 294.6 mg/d, respectively. 81.5%-87.6% of boys and 87.0%
      91.0% of girls had their calcium intakes less than half of the recommended amount
      of adequate intakes. Only 0.2%-0.8% of boys and 0.1%-0.8% of girls had their
      calcium intakes equal or higher than the recommended amount of adequate intakes.
      The sources of dietary calcium were mainly from vegetables, legumes, cereals and
      milk products for Chinese children and adolescents, accounting for more than 70%
      of the average daily intakes. CONCLUSION: During the past two decades, the
      dietary calcium intake of Chinese children and adolescents still remained at
      lower level, suggesting that the optimal food sources of calcium were under
      consumed.

PMID- 24331959
TI  - [Trend in vegetable and fruit intake among Chinese children and adolescents aged
      6 to 17 years from 1991 to 2009 and related socio-demographic factors].
AB  - OBJECTIVE: To analyze the long-term shifts in fruit and vegetable intakes in
      Chinese children and adolescents between 1991 and 2009 and related impact from
      socio-economic factors on such dynamics. METHODS: Data was from the seven waves
      of the China Health and Nutrition Survey. 12 596 children and adolescents aged 6
      to 17 years with full data of 3-day-24-hour dietary recall, together with related
      demographic and socioeconomic factors were chosen as the study subjects. RESULTS:
      The consumption rates of fruits and vegetables showed an significant increasing
      trend, from 58.3% in 1991 to 82.4%, on dark-color vegetables(chi(2) = 213.2, P <
      0.01), from 94.4% to 96.9% on light-color vegetable(chi(2) = 11.6, P < 0.0001)and
      from 12.6% to 45.4% for fruits(chi(2) = 571.2, P < 0.0001)in 2009. The median
      intake of total vegetables decreased from 250.0 g/d in 1991 to 225.8 g/d in
      2009(chi(2) = 72.4, P < 0.0001) and the light-color vegetable decreased by 36.6
      g/d. However, among the corresponding consumers, the fruit intake increased about
      50.0 g/d (chi(2) = 104.2, P < 0.01)and the dark-color vegetable intake decreased
      about 40.0 g/d (chi(2) = 92.8, P < 0.0001 ). The proportion of children who
      reached the minimum intake of vegetable(300 g/d)recommended by Dietary Guidelines
      for Chinese 2007 decreased from 38.9% in 1991 to 26.8% in 2011 and the proportion
      of children who had met the minimum intake(200 g/d)increased from 2.0% to 13.9% .
      25.1% of the children consumed dark-color vegetables more than half of the total
      vegetable intake. Schooling of the mother and family income had important impact
      on fruit consumption of the children. CONCLUSION: Rates on fruit and vegetable
      consumption showed an increasing trend among Chinese children and adolescents
      over the past 20 years. However, the vegetable intake significantly decreased and
      the fruit intake increased slightly. Chinese Children posed a greater risk on
      insufficient intake on both vegetables and fruits. Comprehensive and effective
      programs should be taken to increase vegetable and fruit intakes in order to
      improve the nutritional status of children.

PMID- 24331960
TI  - [A cross-sectional survey on the efficacy of 'China Healthy Lifestyle for All' in
      2012].
AB  - OBJECTIVE: To study the efficacy of 'China Healthy Lifestyle for All' (CHLA).
      METHODS: Under similar GDP status, two counties(one with CHLA and one
      without)were randomly selected from each province of China. Cluster randomized
      sampling method was performed to select 500 over 18-year-olds from each county.
      Face-to-face questionnaire interview was used to collect data related to
      knowledge, awareness and behavior on healthy lifestyle. Generalized Estimated
      Equation was fitted for the multi-factor analysis. RESULTS: A total of 31 396
      subjects were surveyed, with 11 871 urban and 6312 rural residents from counties
      that had under gone the CHLA. Another 3934 urban and 9279 rural subjects were
      from those counties that had not carried out the CHLA(as control group). In both
      urban and rural areas, the CHLA group seemed more likely to be aware of the
      Campaign itself and the knowledge on healthy lifestyle, than the control group as
      well as consciously limiting the salt and oil intake, after adjusting other
      factors such as county, gender, age and education. In the urban area, rates of
      awareness on the Campaign in both the CHLA and control groups were 57.1% and
      31.7% (OR = 3.33, 95% CI:1.63-6.80, P = 0.001)respectively. And in the rural
      area, the rates of consciously limiting the salt intake in the CHLA group and in
      the control group were 51.5% and 38.8% (OR = 1.70, 95% CI:1.13-2.56, P =
      0.011)respectively. In the urban area, subjects from the CHLA group were more
      likely to use the healthy supportive tools than the control group. Rates of using
      salt measuring spoons in both the CHLA group and control groups were 49.2% and
      29.5% (OR = 2.46, 95% CI:1.45-4.17, P = 0.001) respectively. In the rural area,
      statistically significant difference was only found in the rate of using scaled
      oil pots(OR = 2.11, 95% CI:1.09-4.09, P = 0.028)between the CHLA group and the
      control group. In the rural area, the CHLA group was more likely to engage in
      more physical activities than the control group. No differences on the rates
      related to physical activities were found in the urban area. Some behavioral
      indicators such as the rates of consciously maintaining the body weight, daily
      intake of vegetables and fruits showed no statistically significant differences
      between the CHLA group and the control group either in the urban or in the rural
      areas. CONCLUSION: The 'China Healthy Lifestyle for All' seemed to have improved
      the knowledge on awareness and consciousness of healthy lifestyle. However, the
      effect of CHLA on the healthy behavior needs to be further evaluated.

PMID- 24331961
TI  - [Setting up a risk prediction model on metabolic syndrome among 35-74 year-olds
      based on the Taiwan MJ Health-checkup Database].
AB  - OBJECTIVE: This study aimed to provide an epidemiological modeling method to
      evaluate the risk of metabolic syndrome (MS) development in the coming 5 years
      among 35-74 year-olds from Taiwan. METHODS: A cohort of 13 973 subjects aged 35
      74 years who did not have metabolic syndrome but took the initial testing during
      1997-2006 was formed to derive a risk score which tended to predict the incidence
      of MS. Multivariate logistic regression was used to derive the risk functions and
      using the 'check-up center' (Taipei training cohort)as the overall cohort. Rules
      based on these risk functions were evaluated in the remaining three centers (as
      testing cohort). Risk functions were produced to detect the MS on a training
      sample using the multivariate logistic regression models. Started with those
      variables that could predict the MS through univariate models, we then
      constructed multivariable logistic regression models in a stepwise manner which
      eventually could include all the variables. The predictability of the model was
      evaluated by areas under curve (AUC) the receiver-operating characteristic (ROC)
      followed by the testification of its diagnostic property on the testing sample.
      Once the final model was defined, the next step was to establish rules to
      characterize 4 different degrees of risks based on the cut points of these
      probabilities, after being transformed into normal distribution by log
      transformation. RESULTS: At baseline, the range of the proportion of MS was 23.9%
      and the incidence of MS in 5-years was 11.7% in the non-MS cohort. The final
      multivariable logistic regression model would include ten risk factors as: age,
      history of diabetes, contractive pressure, fasting blood-glucose, triglyceride,
      high density lipoprotein cholesterol, low density lipoprotein cholesterol, body
      mass index and blood uric acid. AUC was 0.827(95% CI: 0.814-0.839) that could
      predict the development of MS within the next 5 years. The curve also showed
      adequate performance in the three tested samples, with the AUC and 95% CI as
      0.813 (0.789-0.837), 0.826 (0.800-0.852) and 0.794 (0.768-0.820), respectively.
      After labeling the degrees of the four risks, it was showed that over 17.6% of
      the incidence probability was in the population under mediate risk while over
      59.0% of them was in the high risk group, respectively. CONCLUSION: Both
      predictability and reliability of our Metabolic Syndrome Risk Score Model,
      derived based on Taiwan MJ Longitudinal Health-checkup-based Population Database,
      were relatively satisfactory in the testing cohort. This model was simple, with
      practicable predictive variables and feasible form on degrees of risk. This model
      not only could help individuals to assess the situation of their own risk on MS
      but could also provide guidance on the group surveillance programs in the
      community regarding the development of MS.

PMID- 24331962
TI  - [Effectiveness on the education and food safety programs among senior primary
      students in 2 counties from west China-a cluster randomized trial].
AB  - OBJECTIVE: To evaluate the effectiveness of nutrition and food safety educational
      programs on primary students from grade 4 to 6 in impoverished areas of Western
      China, under a school-based cluster-randomized trial. METHODS: Twelve primary
      schools were selected from 2 impoverished counties in West China and assigned to
      intervention or control groups, randomly, with 6 schools in each group. Self
      rating knowledge, attitude and practice questionnaires were used at both baseline
      and final stages. Textbooks and supportive materials were designed according to
      the characteristics of baseline data. All students in the intervention group were
      treated with targeted nutrition and food safety lectures of 0.5 hour per week for
      2 semesters. Generalized linear mixed effects model was applied to fit the random
      effects on individual and clusters as well as to fit the fixed effect of the
      programs. RESULTS: Three hundred seventy-eight students from grade 4 to 6 were
      randomly selected at the baseline study and the differences of scores on
      knowledge, attitude and practice between the 2 groups were statistically
      insignificant (P > 0.05). No cluster was lost during the trial. In the final
      investigation, 478 students were randomly selected at the individual level.
      Scores on knowledge, attitude and practice among students in the intervention
      group were significantly higher, when comparing to the control group (P < 0.01).
      At the cluster level, more schools in the intervention group showed significant
      changes on knowledge and practice, yet the change in attitude was less obvious.
      Data from the mixed-effects model demonstrated that the program served as an
      influential factor on scores related to knowledge after the intervention(P =
      0.015)but did not affect the scores on related attitude or practice (P > 0.05).
      CONCLUSION: Lectures seemed to have improved the cognition of nutrition and food
      safety among primary students from grade 4 to 6. However, long-term observation
      and larger sample size were needed to evaluate the changes on attitude and
      practice among the students.

PMID- 24331963
TI  - [Relationship between the level of waist circumference and the impaired fasting
      glucose of pre-diabetes].
AB  - OBJECTIVE: To explore the relationship between the level of waist circumference
      (WC) and the impaired fasting glucose (IFG) in people working for the Kailuan
      Enterprise. METHODS: A total of 101 510 subjects from the employees of Kailuan
      Group who took part in the health examination between 2006 to 2007, with fasting
      plasma glucose (FPG) < 6.1 mmol/L, no history of diabetes, completed data on FPG
      and WC examination and without using hypoglycemic agents, were selected as the
      observation cohort. Subjects who did not participate in the health examination
      from 2010 to 2011 and had incomplete data were finally excluded, ended up with 52
      099 subjects available for final analysis. According to the baseline WC
      measurements and its quartile in the health examinations during 2006 to 2007,
      people under observation were divided into four groups (first, second, third and
      the forth quartile groups). Multiple logistic regression analysis was used to
      test the relation between the increasing of WC and IFG. RESULTS: (1) The
      incidence rate of IFG in the obese group was higher than that in non-obese group
      (10.5% vs. 6.8% , P < 0.01), along with an increasing WC noticed in the 4
      quartile groups and the incidence rates of IFG were progressively increased,
      being 6.0%, 7.1%, 8.6% and 11.0% respectively in the total population(7.0%, 7.9%,
      9.1% and 11.4% in males, 2.5%, 4.6%, 6.8% and 9.8% in females). (2)Results from
      the multiple logistic regression analysis showed that, when compared with the
      first quartile group, the second, third and fourth quartile groups had increased
      risks of IFG after adjustment on age, gender and other risk factors in the total
      population, with the OR values being 1.03, 1.15 and 1.30 respectively. After
      adjusting the above factors in genders, we also noticed the increased risks of
      IFG, with the OR value being 1.45, 1.66 and 2.08 in males, while 1.00, 1.09 and
      1.23 in females, respectively. The influence of the second and third quartile
      groups on IFG was not significant in females, however. CONCLUSION: The incidence
      of IFG showed an increasing trend with the increase of WC.

PMID- 24331964
TI  - [Quality of life and related social support for men who have sex with men among
      university students in Chongqing, China].
AB  - OBJECTIVE: To study the status of quality of life(QOL) on men who have sex with
      men (MSM) and it's relationship with social support among university students in
      Chongqing. METHODS: Snowball sampling was applied to recruit the subjects on MSM
      for this study and multistage stratified cluster sampling method was used to
      recruit ordinary male college students. WHOQOL-BREF and SSRS questionnaires were
      used to collect information from both MSM and ordinary male college students.
      RESULTS: Scores from the physiological, psychological, social relations and
      environmental domains for QOL and total QOL were 13.82 +/- 2.25, 13.14 +/- 2.51,
      13.24 +/- 2.96, 12.44 +/- 2.49 and 13.12 +/- 2.16, respectively. Scores for all
      domains of QOL on MSM were lower than figures from ordinary male college students
      (P < 0.05). Results from Canonical correlation analysis revealed that subjective
      support and the use of support, together with psychological and social relations
      were the main factors that influencing the social support and quality of life in
      this population, respectively. CONCLUSION: The improvement of subjective feelings
      and proper use of social support and targeted interventions among this MSM
      population should accord to the different demographic characteristics, especially
      for those who did not have regular sexual partner or in gay circles, and for
      those who practice passive role during sexual act(as "0"), seemed to be helpful
      to improve their quality of life.

PMID- 24331965
TI  - [Gender difference on depressive symptoms among Chinese children and
      adolescents].
AB  - OBJECTIVE: To explore the epidemiological characteristics and gender difference
      of depressive symptoms among Chinese children and adolescents. METHODS: Based on
      the cluster sampling method, 50 boys and 50 girls from each 9.0-18.9 year-olds in
      both urban and rural areas, were recruited from each research center. Children's
      Depression Inventory(CDI)was administered to all the participating students from
      grade 4 to 12 while physical examination indices including pubic hair were
      provided to both boys and girls. Development of breast in girls and genital
      development in boys were also measured. RESULTS: The overall prevalence on
      depressive symptoms was 14.81% for the Chinese adolescents. Boys reported more
      depressive symptoms (15.35%) than that of girls (14.43%). Prevalence related to
      depressive symptoms among children and adolescents from rural areas (16.41%)was
      higher than that of the urban areas(13.23%). Prevalence of depression was higher
      in boys than in girls in both 10-year-old and 11-year-old groups (chi(2) =
      11.625, P < 0.005;chi(2) = 5.807, P < 0.005). In the 17 year-old group,
      prevalence of depression (21.5%)was seen higher in girls than in boys (17.26%)
      (chi (2) = 6.192, P < 0.005). Only in the Tanner stage II , the gender difference
      of depression showed statistically significant (chi(2) = 6.593, P < 0.005), with
      boys as 18.4% and girls as 15.8% . CONCLUSION: The gender differences of
      depression appeared in both special age groups and developmental stages in
      Chinese children that called for further longitudinal study to understand the
      nature of these findings.

PMID- 24331966
TI  - [Study on patients with Creutzfeldt-Jakob disease in Shanghai, 2006-2012].
AB  - OBJECTIVE: To describe the epidemiological characteristics of patients with
      Creutzfeldt-Jakob disease (CJD) in Shanghai from 2006 to 2012. METHODS: Clinical
      and epidemiological information on CJD patients from Shanghai CJD Surveillance
      Network was analyzed. Cerebral spinal fluid (CSF)and blood specimens from
      patients were collected and used for detecting the 14-3-3 protein, and
      polymorphism of 129 amino acid and mutation of PRNP genes. Data was processed by
      EpiData(V3.0)and analyzed by SPSS(V17.0). RESULTS: In totally, one definite CJD
      patient together with 56 probable and 17 possible sporadic CJD patients were
      identified. One E200K genetic CJD case was diagnosed and another one was
      clinically diagnosed. No period- or geographic-related events were observed for
      these cases, but the houses of the two genetic CJD cases were close to each
      other. The mean age of onset of the probable CJD patients was 62 years old which
      was significantly older than that of those possible CJD patients. CONCLUSION:
      Most of the CJD patients identified in Shanghai were sporadic and the number was
      stable from 2006 to 2012. The mean age of onset of those probable CJD patients
      was older than that of the possible CJD patients.

PMID- 24331967
TI  - [Evaluation on the risks of H5, H7 and H9 avian influenza infections in
      Guangzhou: using data from the 2006-2012 avian influenza surveillance program].
AB  - OBJECTIVE: To analyze the results of avian influenza surveillance program in
      Guangzhou from 2006 to 2012 and to evaluate the risk of infections with H5, H7
      and H9 subtypes avian influenza viruses. METHODS: Avian influenza surveillance
      system in Guangzhou consisted five components:serum surveillance on occupational
      population, environmental specimen surveillance of avian influenza virus, avian
      flu emergency surveillance, influenza viruses surveillance on ILI patient and
      surveillance on pneumonia of unknown causes. Hemagglutination inhibition test was
      conducted to detect the antibodies against H5, H7 and H9 while RT-PCR was used to
      test the nucleic acid of H5, H7 and H9 viruses. RESULTS: From 2006 to 2012, 4103
      serum specimens were collected from occupational populations and the overall
      positive rate of H5/H7/H9 antibodies was 3.82% . The antibody positive rates for
      H5, H7 and H9 were 0.22% ,0.00% and 3.70% respectively. 4 serum specimens for H5
      and H9 simultaneously showed antibody positive. The positive rate of H9 among
      occupational populations(4.21%)appeared higher than that from the control
      population(2.16%). 2028 specimens were collected from poultry sites and 55
      samples found positive for H5 nucleic acid (positive rate:2.71%), 14 samples
      positive for H9 nucleic acid (positive rate:0.69%), 5 specimens, simultaneously
      positive for H5 and H9 nucleic acids. However, none of the samples showing H7
      nucleic acid positive. From 2006 to 2012, all the tested H5/H7/H9 virus were
      negative from the respiratory/serum specimens among those close contacts of
      patients or high risk groups through the avian flu emergency surveillance
      program,ILI patient influenza virus surveillance programs or pneumonia of unknown
      causes surveillance program. CONCLUSION: Contamination of H5/H9 avian influenza
      virus did exist in the poultry sites in Guangzhou, especially in the wet Markets.
      The H5/H9 avian influenza virus caused asymptomatic infection was proved to be
      existed within the population exposed to the poultry, suggesting that the poultry
      occupational population in Guangzhou was under the risk of avian influenza virus
      infection.

PMID- 24331968
TI  - [Field epidemiological study on a varicella outbreak among schoolchildren in
      Shenzhen].
AB  - OBJECTIVE: Both epidemiologic characteristics and transmission mode of a
      varicella outbreak among schoolchildren in Shenzhen city were studied and related
      control measures were discussed. METHODS: Case definition was established. Case
      finding and face-to-face investigation were conducted, followed by analysis on
      distributions of time, place and persons of the outbreak. Association between
      possible modes of transmission and the outbreak was explored. Retrospective
      cohort study was carried out. RESULTS: The overall attack rate of this outbreak
      was 4.4% (122 of 2742). The attack rate among primary schoolchildren(8.3%,
      118/1419)was higher than that in the middle-school children(0.3%, 4/1323). There
      were no statistically significant differences on the attack rates between male
      and female students. A total of 22 classes from the 9 grades were affected by
      this outbreak and the aggregation of varicella cases was found in classes. The
      highest attack rates was found in the students of fifth grade(23.7%), followed by
      from the third grade (13.4%). The main transmission mode appeared to be close
      personal contact. The outbreak, with four peaks of incidence, lasted 72 days.
      Data from the investigation suggested that the primary case was introduced into
      the school during military training involved by the students. Activities related
      to physical examination for all the schoolchildren seemed to have contributed to
      the spread of this disease among classes. Delayed isolation of cases appeared to
      be the major factor causing the spread of disease among classes. Intensive off
      school activities or free community bus for children did not seem to be
      associated with the spreading of the disease. 52.5% (64/122) of the cases had
      received one-dose of varicella vaccine, with the median of onset after the
      vaccination as 7 years. The results demonstrated that one single-dose vaccine or
      long vaccination period were factors related to the insufficient immunity that
      causing the outbreak of disease. CONCLUSION: Varicella outbreak has been one of
      the most grievous public health problems in schools, posting challenges on the
      implementation of isolation measures, in particular. Once the chain of
      transmission is in place, it is difficult to make the universal measures
      effective within a short period.

PMID- 24331969
TI  - [A comparative study on medical expenditure for diabetes mellitus and non
      diabetes mellitus in 9 provinces of China, between 2000 and 2009].
AB  - OBJECTIVE: To compare the medical expenditure and its trend for diabetes mellitus
      and non-diabetes mellitus and to assess the direct economic burden of diabetes
      for individuals and families. METHODS: Using data from the China Health and
      Nutrition Survey(CHNS), propensity scores matching(PSM)was used to match diabetes
      mellitus and non-diabetes mellitus according to the related characteristic
      variables. Data from 679 pairs of objects was then compared. RESULTS: From 2000
      to 2009, gaps of annual medical expenditure from diabetes mellitus and non
      diabetes mellitus showed an increase, from 3361.93 to 6608.48 Yuan, with the
      ratios of medical expenditure about 4 times. The ratios of personal economic
      burden and family economic burden had an increase of about 4-5 times. CONCLUSION:
      Compared with non-diabetes mellitus, the annual medical expenses was
      significantly higher among patients with diabetes mellitus. The absolute cost
      appeared a dramatic increase, along with the personal and familiar economic
      burden.

PMID- 24331970
TI  - [A case-control study on the duration of sleeping and cerebral infarction].
AB  - OBJECTIVE: To explore the relationship between duration of sleeping and cerebral
      infarction. METHODS: A case-control study involved 1037 cerebral infarction
      patients admitted by the Second Affiliated Hospital of Harbin Medical
      University,December 2011-December 2012 as cases. Another 1205 adults free from
      cerebro-vascular diseases who had undergone physical examination in the hospital
      at the same period, were served as controls. All the subjects were interviewed
      with unified questionnaire. Chi-square test, u-test and multivariate logistic
      regression analysis were performed. RESULTS: After adjustment for potential
      confounding factors including age, sex, body mass index, wrist-hip ratio,
      smoking, alcohol intake, hypertension, diabetes mellitus, coronary artery disease
      and lipid parameters, data from the multivariate logistic regression analysis
      showed that the risk of cerebral infarction was greater in people who slept less
      than 6 hours per night than those who slept between 6 hours and 8 hours per
      night, with an odds ratio (95% CI)as 2.81 (95% CI:1.68-4.70). There was no
      significant association between factor as 'sleeping longer than 8 hours/pre day'
      and cerebral infarction. Through the subgroup analysis, data showed that the
      association between 'shorter than 6 hour sleep/night' and cerebral infarction
      consistently existed, across the categories of sex, and the degree of association
      was greater in women than in men, with the odds ratio as 5.58 (95% CI: 1.78
      17.52) and 2.00 (95% CI:1.10-3.64) respectively. CONCLUSION: Short sleeping
      duration might increase the risk of developing cerebral infarction.

PMID- 24331971
TI  - [Methodological quality of Meta-analyses regarding studies related to genetic
      association on papers published in Chinese journals].
AB  - OBJECTIVE: To assess the methodological quality of Meta-analyses on papers
      published in Chinese journals regarding studies on genetic association. METHODS:
      Meta-analyses of genetic association study published in Chinese journals up to
      December 2012 had been searched through on 4 Chinese electronic databases(China
      biomedicine database, CNKI, Wanfang database and VIP Information). Articles
      independently selected by both two researchers under definite inclusion and
      exclusion criteria were included in this study(with consultation on a third
      researcher if inconsistent opinions existed). A Measurement Tool for the
      Assessment of Multiple Systematic Reviews (AMSTAR) checklist was used to evaluate
      the methodological quality together with the methodological quality score being
      calculated. RESULTS: Totally, 440 articles were included in this study, with mean
      score of the methodological quality score(maximum score is 11)as 5.77. Among the
      440 articles, none had met the requirement of total 11 items in AMSTAR, with
      89.5% and 38.6% of them had a priori design or duplicate study selection and data
      extraction. 72.7% of them performed a comprehensive literature search and 14.8%
      included studies regardless of their publication status. 10.9% and 92.5% of them
      provided a list of including or excluding studies or stated characteristics of
      the included ones. 32.0% of them assessed the scientific quality of those
      included studies, with 50.0% of them mentioned their qualities when formulating
      the conclusions. 93.2% of them used appropriate methods to combine data while
      82.3% assessed the likelihood of publication bias. 0.5% of them declared the
      conflict of interests. CONCLUSION: Our results from Meta-analyses showed an
      acceptable quality regarding their methodology related to genetic association on
      papers being published in Chinese journals. Improvement is needed especially on
      aspects as:selection of studies, data extraction, publication status with list of
      inclusion and exclusion, quality assessment and declaration on conflict of
      interests, etc.

PMID- 24331972
TI  - [Relationship between temperature and the risks of mortality in China: a Meta
      analysis].
AB  - OBJECTIVE: To understand the effect of temperature on the risk of mortality and
      the modification effect of latitude, in China. METHODS: Relevant papers were
      searched and Meta-analysis was used to determine the exposure-response
      relationship for each health outcome which was associated with the exposure to
      temperature. Meta-regression analysis was used to evaluate the effect
      modification by latitude. RESULTS: Ten studies in 15 cities were included in the
      study. When temperature increased by one centigrade, the risks of mortality
      showed the following changes:deaths from non-accidental increased by 2%
      (95%CI:1%, 3%), from cardiovascular disease increased by 4% (95%CI:2%, 6%)and
      from the respiratory disease increased by 2% (95%CI:1%, 4%). As temperature
      decreased by one centigrade, the mortality risks of the following diseases showed
      the changes as: non-accidental death increased by 4% (95% CI:2%, 7%),
      cardiovascular disease increased by 4% (95%CI:1%, 7%)and the respiratory diseases
      increased by 2% (95%CI:0%, 4%). When latitude ranged from 0 to 25, 26 to 30, 31
      to 39 degree or over 40 degrees, respectively and the temperature decreased by
      one centigrade, the mortality risks of the general population increased by 6.5%
      (95%CI:-2.7%, 15.6%), 5.8% (95% CI:2.4%, 9.3%),0.8% (95%CI:0.4%, 1.2%),0.5%
      (95%CI: -0.5%, 1.5%). As temperature increased by one centigrade, mortality risk
      of the general population increased by 0.6% (95%CI:-0.3%, 1.4%), 1.9%
      (95%CI:0.7%, 3.1%), 2.0% (95%CI:1.0%, 3.0%) and 5.8% (95% CI:-3.2%, 14.8%). As
      latitude increased by five degrees with high temperature, the mortality risk of
      general people increased by 0.3% (95% CI:0.1% ,0.8%) while decreased by 0.8% (95%
      CI:0.5%, 0.9%) under low temperature. CONCLUSION: In China, the mortality risk
      increased along with the changes of temperature. The adaptability to coldness
      among people living in high latitude areas seemed to be stronger than those
      living in other areas of latitudes. Who were more vulnerable to high temperature.

PMID- 24331973
TI  - [Non-parametric Bootstrap estimation on the intraclass correlation coefficient
      generated from quantitative hierarchical data].
AB  - This paper aims to achieve Bootstraping in hierarchical data and to provide a
      method for the estimation on confidence interval(CI) of intraclass correlation
      coefficient(ICC).First, we utilize the mixed-effects model to estimate data from
      ICC of repeated measurement and from the two-stage sampling. Then, we use
      Bootstrap method to estimate CI from related ICCs. Finally, the influences of
      different Bootstraping strategies to ICC's CIs are compared. The repeated
      measurement instance show that the CI of cluster Bootsraping containing the true
      ICC value. However, when ignoring the hierarchy characteristics of data, the
      random Bootsraping method shows that it has the invalid CI. Result from the two
      stage instance shows that bias observed between cluster Bootstraping's ICC means
      while the ICC of the original sample is the smallest, but with wide CI. It is
      necessary to consider the structure of data as important, when hierarchical data
      is being resampled. Bootstrapping seems to be better on the higher than that on
      lower levels.

PMID- 24331974
TI  - [How to write high-quality epidemiological research paper III. Reporting
      recommendations for Tumor Marker Prognostic Studies(REMARK)-introduction and
      explanation].

PMID- 24331975
TI  - [Statistical methods on the estimation of relative risk or prevalence ratio].

PMID- 24331976
TI  - [Translational epidemiology].

PMID- 24331977
TI  - Chlorthalidone versus hydrochlorothiazide in hypertension treatment: do we have
      the evidence to decide?

PMID- 24331978
TI  - ESRD care within the US Department of Veterans Affairs: a forward-looking program
      with an illuminating past.
AB  - The first governmental agency to provide maintenance hemodialysis to patients
      with end-stage renal disease (ESRD) was the Veterans Administration (VA; now the
      US Department of Veterans Affairs). Many historical VA policies and programs set
      the stage for the later care of both veteran and civilian patients with ESRD.
      More recent VA initiatives that target restructuring of care models based on
      quality management, system-wide payment policies to promote cost-effective
      dialysis, and innovation grants aim to improve contemporary care. The VA
      currently supports an expanded and diversified nationwide treatment program for
      patients with ESRD using an integrated patient-centered care paradigm. This
      narrative review of ESRD care by the VA explores not only the medical advances,
      but also the historical, socioeconomic, ethical, and political forces related to
      the care of veterans with ESRD. 

PMID- 24331979
TI  - Role of p38, ERK1/2, focal adhesion kinase, RhoA/ROCK and cytoskeleton in the
      adipogenesis of human mesenchymal stem cells.
AB  - Adipogenesis is important to health and is thought occurring in the two stages of
      mesenchymal stem cell commitment to a preadipocyte fate and terminal
      differentiation of the preadipocyte. However, the mechanism of adipogenesis is
      still not clear. In this study, the roles of p38, extracellular regulated protein
      kinases 1/2 (ERK1/2), focal adhesion kinase (FAK), RhoA/ROCK, and cytoskeleton in
      both of the two stages of adipogenesis were assayed. Our results showed that the
      treatments of SB203580 (the inhibitor of p38) and U0126 (the inhibitor of ERK1/2)
      suppressed the adipogenesis induced by differentiation medium, and the treatments
      of PF573228 (a specific inhibitor of FAK), Y27632 (a specific inhibitor of
      RhoA/ROCK) and cytochalasin D (an inhibitor of cytoskeletal organization)
      promoted the adipogenesis. The treatments of SB203580 and U0126 significantly
      inhibited the adipogenic differentiation of hMSCs cultured in differentiation
      medium in the presence of PF573228, Y27632 or cytochalasin D. Moreover, the
      treatments of PF573228, Y27632 and cytochalasin D promoted p38 and ERK1/2
      phosphorylations, and the treatments of U0126 and SB203580 decreased p38 and
      ERK1/2 phosphorylations, respectively. These results demonstrated that p38 and
      ERK1/2 played crucial positive roles in adipogenesis, and FAK, RhoA/ROCK and
      cytoskeleton played negative roles. Furthermore, FAK, RhoA/ROCK and cytoskeleton
      affected adipogenesis by regulating the activities of p38 and ERK1/2 which
      interacted with each other in the process of adipogenesis.

PMID- 24331980
TI  - Differential expression and elution behavior of basic 7S globulin among cultivars
      under hot water treatment of soybean seeds.
AB  - Basic 7S globulin (Bg7S), which accumulates in mature soybean (Glycine max)
      seeds, is an extracellular matrix protein. A large amount of Bg7S is synthesized
      de novo and is eluted from soybean seeds when immersed in 50-60 degrees C water
      (hot water treatment, HWT). However, the Bg7S elution mechanism remains unclear.
      Under HWT, the seeds probably undergo heat stress and flooding stress. To obtain
      fundamental knowledge related to how Bg7S is eluted from hot-water-treated seeds,
      this study compared Bg7S elution among soybean cultivars having different
      flooding tolerance during pre-germination. The amounts of Bg7S eluted from seeds
      varied significantly among cultivars. Elution was suppressed by seed coats
      regarded as preventing the leakage of seed contents by rapid water imbibition.
      Furthermore, Bg7S expression levels differed among cultivars, although the
      difference did not result from any variation in Bg7S promoter sequences. However,
      the expression levels of Bg7S under HWT were not associated with the flooding
      tolerance level. Immunoelectron microscopy revealed that the Bg7S accumulated in
      the intercellular space of hot-water-treated seeds. Plasma membrane shrinkage was
      observed. The main proteins eluted from seeds under HWT were located in the
      extracellular space. This study clarified the mechanism of Bg7S elution from
      seeds under HWT. 

PMID- 24331981
TI  - Characterization of an alkalophilic extracellular chitosanase from Bacillus
      cereus GU-02.
AB  - An alkalophilic extracellular chitosanase (ACTase) was characterized from the
      culture supernatant of Bacillus cereus GU-02. Kinetic properties of ACTase
      produced from B. cereus GU-02 after cultivation in anaerobic condition, alkaline
      medium (pH 10) at 37 degrees C for 3 days were investigated. ACTase was found to
      be stable in alkaline pH range from 8 to 10. Interestingly, optimum pH and
      temperature were estimated to be 10 and 37 degrees C, respectively, where ACTase
      showed chitosan degrading activity (87%), which was enhanced by 15% in the
      presence of calcium ions (8 mM). The ACTase produced from B. cereus GU-02 was
      partially purified from the culture supernatant, and its enzymatic activity was
      kinetically characterized. The Vmax and Km were estimated with a chitosan (degree
      of deacetylation, DD 92% as substrate) as 0.038 U/min/MUg protein and 0.327 MUM,
      respectively. A combination of the TLC and MALDI-TOF MS results showed that the
      chitosan oligosaccharides obtained from the hydrolysis of high molecular weight
      chitosan (HMWC) by ACTase of the B. cereus GU-2 comprise oligomers with degree of
      polymerization (DP) mainly from dimers to pentamers. High production of ACTase
      and chitooligosaccharides may be useful for various industrial and biological
      applications. 

PMID- 24331982
TI  - Culture of a high-chlorophyll-producing and halotolerant Chlorella vulgaris.
AB  - In order to increase the value of freshwater algae as raw ingredients for health
      foods and feed for seawater-based farmed fish, we sought to breed high
      chlorophyll halotolerant Chlorella with the objective of generating strains with
      both high chlorophyll concentrations (>= 5%) and halotolerance (up to 1% NaCl).
      We used the Chlorella vulgaris K strain in our research institute culture
      collection and induced mutations with UV irradiation and acriflavine which is
      known to effect mutations of mitochondrial DNA that are associated with
      chlorophyll production. Screenings were conducted on seawater-based "For
      Chlorella spp." (FC) agar medium, and dark-green-colored colonies were visually
      selected by macroscopic inspection. We obtained a high-chlorophyll halotolerant
      strain (designated C. vulgaris M-207A7) that had a chlorophyll concentration of
      6.7% (d.m.), a level at least three-fold higher than that of K strain. This
      isolate also exhibited a greater survival rate in seawater that of K strain.

PMID- 24331983
TI  - Effect of preoperative acetaminophen/hydrocodone on the efficacy of the inferior
      alveolar nerve block in patients with symptomatic irreversible pulpitis: a
      prospective, randomized, double-blind, placebo-controlled study.
AB  - INTRODUCTION: The purpose of this prospective, randomized, double-blind, placebo
      controlled study was to determine the effect of the administration of the
      combination acetaminophen/hydrocodone on the anesthetic success of mandibular
      posterior teeth in patients experiencing symptomatic irreversible pulpitis.
      METHODS: One hundred emergency patients in moderate to severe pain diagnosed with
      symptomatic irreversible pulpitis of a mandibular posterior tooth randomly
      received, in a double-blind manner, identical capsules of either a combination
      dose of 1000 mg acetaminophen/10 mg hydrocodone or placebo 60 minutes before the
      administration of a conventional inferior alveolar nerve (IAN) block. Endodontic
      access was begun 15 minutes after completion of the block, and all patients used
      for data analysis had profound lip numbness. Success was defined as no or mild
      pain (visual analog scale recordings) on pulpal access or instrumentation.
      RESULTS: The success rate for the IAN block was 32% for the combination dose of
      1000 mg acetaminophen/10 hydrocodone and 28% for the placebo dose, with no
      statistically significant difference between the 2 groups (P = .662).
      CONCLUSIONS: A combination dose of 1000 mg acetaminophen/10 mg hydrocodone given
      60 minutes before the administration of the IAN block did not result in a
      statistically significant increase in anesthetic success for mandibular posterior
      teeth in patients experiencing symptomatic irreversible pulpitis.

PMID- 24331984
TI  - Human cytomegalovirus and Epstein-Barr virus in etiopathogenesis of apical
      periodontitis: a systematic review.
AB  - INTRODUCTION: During the last decade, a hypothesis has been established that
      human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) may be implicated in
      the pathogenesis of apical periodontitis. The aim of this review was to analyze
      the available evidence that indicates that HCMV and EBV can actually contribute
      to the pathogenesis of periapical lesions and to answer the following focused
      question: is there a relationship between HCMV and EBV DNA and/or RNA detection
      and the clinical features of human periapical lesions? METHODS: The literature
      search covered MEDLINE, Science Citation Index Expanded (SCIexpanded), Scopus,
      and The Cochrane Library database. Quantitative statistical analysis was
      performed on the pooled data of HCMV and EBV messenger RNA transcripts in tissues
      of symptomatic and asymptomatic periapical lesions. RESULTS: The electronic
      database search yielded 48 hits from PubMed, 197 hits from Scopus, 40 hits from
      Web of Science, and 1 from the Cochrane Library. Seventeen cross-sectional
      studies have been included in the final review. The pooled results from
      quantitative systematic method analysis showed no statistically significant
      relationship between the presence of HCMV and EBV messenger RNA transcripts (P =
      .083 and P = .306, respectively) and the clinical features of apical
      periodontitis. CONCLUSIONS: The findings of HCMV and EBV transcripts in apical
      periodontitis were controversial among the included studies. Herpesviruses were
      common in symptomatic and large-size periapical lesions, but such results failed
      to reach statistical significance. Further studies, including those based on an
      experimental animal model, should provide more data on herpesviruses as a factor
      in the pathogenesis of periapical inflammation.

PMID- 24331985
TI  - Nonendodontic lesions misdiagnosed as apical periodontitis lesions: series of
      case reports and review of literature.
AB  - INTRODUCTION: This study aimed to analyze cases referred from a reference service
      in oral pathology that were initially misdiagnosed as periapical lesions of
      endodontic origin and to perform a review of the literature regarding lesions
      located in the apical area of teeth with a nonendodontic source. METHODS: A
      survey was made of clinical cases derived from the service of oral pathology from
      2002 to 2012. The pertinent literature was also reviewed using ScienceDirect and
      PubMed databases. The lesions were grouped into benign lesions mimicking
      endodontic periapical lesions (BLMEPLs), malignant lesions mimicking endodontic
      periapical lesions (MLMEPLs), and Stafne bone cavities. The clinical
      presentations were divided into lesions with swelling without pain, lesions with
      swelling and pain, and lesions without swelling but presenting with pain.
      RESULTS: The results showed that 66% (37/56) of cases represented benign lesions,
      29% (16/56) malignant lesions, and 5% (3/56) Stafne bone cavities. The most
      commonly reported BLMEPLs were ameloblastomas (21%) followed by nasopalatine duct
      cysts (13.5%). The most frequently cited MLMEPLs were metastatic injuries (31.5%)
      followed by carcinomas (25%). The main clinical presentation of BLMEPLs was pain,
      whereas that of MLMEPLs was swelling associated with pain; Stafne bone cavities
      displayed particular clinical findings. CONCLUSIONS: Clinical and radiologic
      aspects as well as the analysis of the patients' medical history, pulp vitality
      tests, and aspiration are essential tools for developing a correct diagnosis of
      periapical lesions of endodontic origin. However, if the instruments mentioned
      earlier indicate a lesion of nonendodontic origin, a biopsy and subsequent
      histopathological analysis are mandatory.

PMID- 24331986
TI  - Effect of 1440-nanometer neodymium:yttrium-aluminum-garnet laser irradiation on
      pain and neuropeptide reduction: a randomized prospective clinical trial.
AB  - INTRODUCTION: The purpose of this study was to investigate the efficacy of a 1440
      nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser on relieving pain in relation
      to the levels of inflammatory cytokine and neuropeptides in the root canal
      exudates of teeth with persistent symptomatic apical periodontitis. METHODS:
      Forty teeth with persistent symptomatic apical periodontitis were randomly
      assigned to treatment groups: group L, intracanal irradiation of 1440-nm Nd:YAG
      laser with a 300-MUm-diameter fiberoptic tip in addition to conventional root
      canal retreatment, and group C, conventional root canal re-treatment. The degrees
      of both spontaneous pain and the pain on percussion before and after treatment
      were recorded, and root canal exudate samples were collected to quantify the
      associated levels of substance P, calcitonin gene-related peptide (CGRP), and
      matrix metalloproteinase (MMP)-8 by immunoassay. RESULTS: All of the measured
      parameters were significantly reduced in group L (P < .05), whereas the level of
      pain on percussion, CGRP, and MMP-8 were significantly reduced in group C (P <
      .05). The 1440-nm Nd:YAG laser had significantly better effect on the relief of
      pain on percussion and the reduction of substance P, CGRP, and MMP-8 levels. The
      visual analog scale scores of perceived pain correlated with pain-related
      neuropeptides and inflammatory cytokine levels in root canal exudates.
      CONCLUSIONS: The 1440-nm Nd:YAG laser irradiation via fiberoptic tip to the teeth
      with persistent apical periodontitis provided promising consequences of pain and
      inflammation modulation.

PMID- 24331987
TI  - Susceptibility of as-yet-uncultivated and difficult-to-culture bacteria to
      chemomechanical procedures.
AB  - INTRODUCTION: A significant portion of the bacteria taking part of the microbiome
      associated with apical periodontitis still remain to be cultivated and
      phenotypically characterized. This molecular study evaluated the prevalence of
      selected as-yet-uncultivated and difficult-to-culture bacterial taxa in infected
      root canals and their susceptibility to chemomechanical procedures. METHODS: Root
      canals of single-rooted teeth with apical periodontitis were prepared using
      rotary nickel-titanium instruments and 2.5% sodium hypochlorite as the irrigant.
      DNA extracts from samples taken before (S1) and after (S2) chemomechanical
      preparation were surveyed for the presence of 7 as-yet-uncultivated phylotypes
      and 1 difficult-to-culture species using end-point polymerase chain reaction.
      Samples were also subjected to quantitative analysis of total bacteria and levels
      of the 2 most prevalent taxa. RESULTS: Bacteroidaceae sp. HOT-272 (24%) and
      Fretibacterium fastidiosum (20%) were the most prevalent taxa in S1. Their mean
      counts in S1 were 8.25 * 10(3) and 2.13 * 10(3) rRNA gene copies, corresponding
      to 0.18% and 0.55% of the total bacteria. Chemomechanical debridement promoted a
      highly statistically significant reduction in total bacterial counts (P < .001),
      but 64% of the canals were still positive for bacterial presence. Of the target
      taxa, only Bacteroidaceae sp. HOT-272 and F. fastidiosum were detected in S2
      (each one in 1 sample). The reduction in counts of both taxa was also highly
      significant (P < .001). CONCLUSIONS: Findings confirmed that several as-yet
      uncultivated and difficult-to-grow bacterial taxa can participate in the
      microbiome associated with apical periodontitis. Two of them were found in
      relatively high prevalence but rarely as a dominant species. Chemomechanical
      procedures were highly effective in completely eliminating these taxa or at least
      substantially reducing their numbers.

PMID- 24331988
TI  - Effect of working length measurement by electronic apex locator or digital
      radiography on postoperative pain: a randomized clinical trial.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of working length
      determination methods, electronic apex locator and digital radiography, on
      postoperative pain. METHODS: Two hundred twenty patients with asymptomatic single
      rooted vital teeth were randomly assigned to 2 groups according to the method
      used for working length determination, the radiographic group and the electronic
      apex locator group. After working length determination, chemomechanical
      preparation was performed in a crown-down technique with ProTaper instruments. A
      master cone radiograph was taken. Canals were obturated with gutta-percha and
      sealer by using a lateral compaction technique. Postoperative pain was assessed
      after 4, 6, 12, 24, and 48 hours by using a 4-point pain intensity scale. In
      addition, patients were asked to record the number of days necessary to achieve
      complete pain resolution. RESULTS: Postoperative pain during the 4-hour to 48
      hour interval studied was not significantly different (P > .05) between groups.
      The mean times for pain dissipation in the radiographic and electronic apex
      locator groups were 3.37 +/- 2.79 and 3.88 +/- 3.34 days, respectively. The
      difference between groups was not statistically significant (P > .05).
      CONCLUSIONS: There is no difference in postoperative pain between working length
      measurement methods by using an electronic apex locator or digital radiography.
      The reduced exposure to radiation by using apex locator may be a factor that
      influences a dentist's decision to choose the electronic apex locator over
      radiography.

PMID- 24331989
TI  - Detection of various anatomic patterns of root canals in mandibular incisors
      using digital periapical radiography, 3 cone-beam computed tomographic scanners,
      and micro-computed tomographic imaging.
AB  - INTRODUCTION: The purpose of this study was to compare the accuracy of digital
      periapical (PA) radiography and 3 cone-beam computed tomographic (CBCT) scanners
      in the identification of various internal anatomic patterns in mandibular
      incisors. METHODS: Forty mandibular incisors were scanned using micro-computed
      tomographic imaging as the gold standard to establish the internal anatomic
      pattern. The number of root canals and internal patterns were classified into
      type I (single canal, n = 12), type Ia (single oval canal, n = 12), and type III
      (2 canals, n = 16). The teeth were placed in a human mandible, and digital PA
      radiography and 3 CBCT scans (Kodak 9000 3D [Carestream Health, Rochester, NY],
      Veraviewepocs 3De [J Morita MFG Corp, Kyoto, Japan], NewTom 5G [QR Srl, Verona,
      Italy]) were performed. Two blinded examiners classified each tooth's anatomic
      pattern, which were then compared with the micro-computed tomographic
      determinations. RESULTS: Considering type I and type Ia, which both presented
      with 1 root canal, there was a high degree of accuracy for all methods used (P >
      .05). The same result was found for type III. When identifying the shape of
      single canals (type I), CBCT imaging was more accurate compared with PA
      radiography. Concerning oval canals (type Ia), there was a significant difference
      between PA radiography and NewTom CBCT (PA radiography = 44%, NewTom = 88%).
      However, there were no significant differences between the 3 CBCT units.
      CONCLUSIONS: Double-exposure digital PA radiography for mandibular incisors is
      sufficient for the identification of the number of root canals. All CBCT devices
      showed improved accuracy in the identification of single root canal anatomy when
      a narrow canal was present. However, the identification of oval canals was
      improved only with the NewTom CBCT device.

PMID- 24331991
TI  - Concentration-dependent effect of sodium hypochlorite on stem cells of apical
      papilla survival and differentiation.
AB  - INTRODUCTION: Intracanal disinfection is a crucial step in regenerative
      endodontic procedures. Most published cases suggest the use of sodium
      hypochlorite (NaOCl) as the primary irrigant. However, the effect of clinically
      used concentrations of NaOCl on the survival and differentiation of stem cells is
      largely unknown. In this study, we tested the effect of various concentrations of
      NaOCl on the stem cells of the apical papilla (SCAPs) survival and dentin
      sialophosphoprotein (DSPP) expression. METHODS: Standardized root canals were
      created in extracted human teeth and irrigated with NaOCl (0.5%, 1.5%, 3%, or 6%)
      followed by 17% EDTA or sterile saline. SCAPs in a hyaluronic acid-based scaffold
      were seeded into the canals and cultured for 7 days. Next, viable cells were
      quantified using a luminescence assay, and DSPP expression was evaluated using
      quantitative real-time polymerase chain reaction. RESULTS: There was a
      significant reduction in survival and DSPP expression in the group treated with
      6% NaOCl compared with the untreated control group. Comparable survival was
      observed in the groups treated with the lower concentrations of NaOCl, but
      greater DSPP expression was observed in the 1.5% NaOCl group. In addition, 17%
      EDTA resulted in increased survival and DSPP expression partially reversing the
      deleterious effects of NaOCl. CONCLUSIONS: Collectively, the results suggest that
      dentin conditioning with high concentrations of NaOCl has a profound negative
      effect on the survival and differentiation of SCAPs. However, this effect can be
      prevented with the use of 1.5% NaOCl followed by 17% EDTA. The inclusion of this
      irrigation regimen might be beneficial in regenerative endodontic procedures.

PMID- 24331990
TI  - A standardized novel method to measure radiographic root changes after endodontic
      therapy in immature teeth.
AB  - INTRODUCTION: Outcome studies of endodontic treatment of necrotic immature
      permanent teeth rely on radiographic measures as surrogates of whether the
      treatment achieved regeneration/revascularization/revitalization. An increase in
      radiographic root length and/or width is thought to result in a better long-term
      prognosis for the tooth. In this study, a method to measure radiographic outcomes
      of endodontic therapies on immature teeth was developed and validated. METHODS: A
      standardized protocol was developed for measuring the entire area of the root of
      immature teeth. The radiographic root area (RRA) measurement accounts for the
      entire surface area of the root as observed on a periapical radiograph. Reviewers
      were given instructions on how to measure RRA, and they completed measurements on
      a set of standardized radiographs. RESULTS: The intraclass correlation between
      the 4 reviewers was 0.9945, suggesting a high concordance among reviewers. There
      was no effect of the reviewer on the measured RRA values. High concordance was
      also observed when 1 rater repeated the measurements, with an intraclass
      correlation value of 0.9995. There was no significant difference in RRA values
      measured at the 2 sessions by the same rater. Furthermore, significant
      differences in RRA were detectable between clinical cases that showed obvious
      continued root development and cases that did not demonstrate discernible root
      development. CONCLUSIONS: These results suggest that RRA is a valid measure to
      assess radiographic outcomes in endodontically treated immature teeth, and RRA
      should be useful in future clinical studies of regenerative endodontic outcomes.

PMID- 24331992
TI  - Imbalance of interleukin-17+ T-cell and Foxp3+ regulatory T-cell dynamics in rat
      periapical lesions.
AB  - INTRODUCTION: Interleukin (IL)-17(+) T-helper (Th17) cells and Foxp3(+)
      regulatory T (Treg) cells are CD4(+) T-helper cells with reciprocal functions in
      immunology and bone metabolism. The present study aimed to investigate the
      expression dynamics of Th17 and Treg cells in rat periapical lesions as well as
      their correlation with bone resorption. METHODS: Experimental pulp exposures were
      made in the lower first molars of 28 Wistar rats to induce periapical lesions.
      Rats were killed on days 0, 7, 21, and 35. Mandibles were prepared for micro
      computed tomography scanning, histologic observation, immunohistochemistry,
      enzyme histochemistry, and double immunofluorescence analysis. RESULTS: Through 3
      dimensional and 2-dimensional measurements, the volume and area of periapical
      lesions visibly increased from day 7 to day 21 and then expanded slowly between
      days 21 and 35. IL-17-positive cells markedly increased from day 7 to day 35.
      However, Foxp3-positive cells remained at low levels until day 21 and then
      dramatically increased by day 35. The IL-17(+)/Foxp3(+) ratio and number of
      osteoclasts simultaneously increased from day 7 to day 21 and then decreased on
      day 35. Finally, the distinct distribution of CD4(+)/IL-17(+) Th17 and
      CD4(+)/Foxp3(+) Treg cells was observed on days 7 and 35. CONCLUSIONS: Our
      findings imply the imbalance of IL-17(+) T cell and Foxp3(+) Treg cell dynamics
      in induced periapical lesions, which may play an important role in periapical
      lesion progression.

PMID- 24331993
TI  - Distribution of mast cells and macrophages and expression of interleukin-6 in
      periapical cysts.
AB  - INTRODUCTION: Mast cells and macrophages are important components of the
      inflammatory infiltrate found in inflammatory periapical diseases. Several
      cytokines participate in the mechanisms of inflammation, tissue repair, and bone
      resorption associated with periapical cysts. The aim of the present study was to
      evaluate the distribution of mast cells and macrophages and the expression of
      interleukin-6 (IL-6) in periapical cysts. METHODS: Thirty periapical cysts were
      selected for the study, and clinical, demographic, and gross information from the
      cases was obtained from the laboratory records. Five-micrometer sections stained
      with hematoxylin-eosin were reviewed for analysis of the microscopic features of
      the cysts, and 3-MUm sections on silanized slides were used for
      immunohistochemical reactions with anti-tryptase, anti-CD68, and anti-IL-6.
      RESULTS: There was no statistically significant difference in the mean number of
      mast cells and macrophages when comparing superficial and deep regions of the
      fibrous capsule of the cysts. Mean number of mast cells on the superficial region
      of the fibrous capsule was higher in cysts showing intense superficial
      inflammation and exocytosis. Macrophages were more commonly found in areas
      showing IL-6 expression, and IL-6 was less expressed in deep regions of the
      fibrous capsule in cysts showing greater gross volume. CONCLUSIONS: The results
      reinforced the participation of mast cells and macrophages in the pathogenesis of
      periapical cysts and suggested that IL-6 is not the major bone resorption
      mediator in larger periapical cysts.

PMID- 24331995
TI  - Role of miR-424 on angiogenic potential in human dental pulp cells.
AB  - INTRODUCTION: Growing evidence shows microRNAs (miRNAs) regulate numerous
      cellular processes. The purpose of this study was to investigate whether miRNAs
      can regulate the commitment of human dental pulp cells (hDPCs) to the angiogenic
      fate. METHODS: The hDPCs were induced to differentiate into the vascular lineage.
      Gene expression of endothelial markers (vWF and CD31) on day 7 after induction
      was analyzed by using quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR).The miRNA expression profiling of endothelial differentiation
      was performed by microarray and was validated by qRT-PCR analysis. The hDPCs were
      infected by recombinant lentivirus to overexpress or knock down miR-424 stably,
      and the biological effects of miR-424 on the endothelial differentiation of hDPCs
      were further investigated. The tube formation ability and the amount of
      endothelial markers (vWF and KDR) were evaluated by Matrigel assay and Western
      blotting. Target genes of miR-424 were further determined by bioinformatic
      algorithms and Western blotting. RESULTS: After endothelial differentiation, the
      expression of vWF and CD31 increased significantly in hDPCs. Microarray data
      showed that the miR-424 expression level was down-regulated on day 7. The qRT-PCR
      revealed a time-dependent decrease, with significant differences detected on day
      1 and day 7 (P < .05). Knockdown of miR-424 expression in hDPCs promoted
      endothelial differentiation, with increased tube formation and up-regulated
      expression of vWF and KDR. In contrast, overexpression of miR-424 inhibited their
      differentiation. In addition, miR-424 was predicted to target vascular
      endothelial growth factor and KDR. Overexpression of miR-424 decreased vascular
      endothelial growth factor and KDR protein levels, whereas miR-424 inhibition
      significantly elevated them. CONCLUSIONS: This study demonstrated that miR-424
      may play a negative role in regulating endothelial differentiation of hDPCs, and
      inhibition of miR-424 may contribute to dental pulp repair and regeneration.

PMID- 24331994
TI  - Lipopolysaccharide enhances Wnt5a expression through toll-like receptor 4,
      myeloid differentiating factor 88, phosphatidylinositol 3-OH kinase/AKT and
      nuclear factor kappa B pathways in human dental pulp stem cells.
AB  - INTRODUCTION: Lipopolysaccharide (LPS) has been implicated in mesenchymal stem
      cell differentiation processes. Wnt5a, one of the "non-canonical" Wnt family
      members, is important in signaling stem cell differentiation and in the
      inflammatory responses of immune cells. Here we studied whether LPS can regulate
      the expression of Wnt5a in human dental pulp stem cells (hDPSCs) and investigated
      the intracellular signaling pathways activated by LPS. METHODS: Wnt5a mRNA and
      protein expression changes in hDPSCs were investigated by real-time polymerase
      chain reaction analysis and enzyme-linked immunosorbent assay. In addition, real
      time polymerase chain reaction, enzyme-linked immunosorbent assay, and luciferase
      activity assays were used to determine whether toll-like receptor 4 (TLR4),
      myeloid differentiating factor 88 (MyD88), nuclear factor kappa B (NF-kB), or the
      phosphatidylinositol 3-OH kinase (PI3K)/AKT pathways are involved in LPS-induced
      Wnt5a expression. The activation of PI3K and AKT in hDPSCs was measured by
      Western blot analysis. RESULTS: Wnt5a mRNA and protein expression was rapidly
      increased in response to LPS in a time- and dose-dependent manner. LPS-induced
      Wnt5a expression was effectively attenuated by administration of a TLR4
      neutralizing antibody, MyD88 inhibitory peptide, PI3-kinase inhibitors (LY294002
      and wortmannin), an AKT inhibitor, or NF-kappaB inhibitor (pyrrolidine
      dithiocarbamate), IkappaBa phosphorylation inhibitor (Bay 117082), or IkappaB
      protease inhibitor (L-1-tosylamido-2-phenylethyl chloromethyl ketone). Treatment
      of hDPSCs with LPS activated PI3-kinase (p85) and AKT signaling in a time
      dependent manner. Moreover, LPS-mediated increases in kappaB-luciferase activity
      were diminished by the overexpression of dominant negative mutants of TLR4,
      MyD88, p85, AKT, and IkappaBa. CONCLUSIONS: These results demonstrated that LPS
      induced Wnt5a expression was mediated through the TLR4/MyD88/PI3-kinase/AKT
      pathway, which then initiated NF-kappaB activation in hDPSCs.

PMID- 24331996
TI  - Ionic extraction of a novel nano-sized bioactive glass enhances differentiation
      and mineralization of human dental pulp cells.
AB  - INTRODUCTION: This study aimed to investigate the effects of a novel nano-sized
      58S bioactive glass (nano-58S BG) on the odontogenic differentiation and
      mineralization of human dental pulp cells (hDPCs) in vitro. METHODS: Extractions
      were prepared by incubating nano-58S BG, 45S5 BG, or 58S BG particulates in
      Dulbecco modified Eagle medium at 1% w/v for 24 hours and were filtrated through
      0.22-MUm filters. The supernatants were used as BG extractions. The hDPCs were
      cultured in nano-58S BG, 45S5 BG, and 58S BG extractions. The proliferation of
      hDPCs was evaluated using the methylthiazol tetrazolium assay. Odontogenic
      differentiation was evaluated based on the real-time polymerase chain reaction of
      differentiation- and mineralization-related genes, namely, alkaline phosphatase
      (ALP), collagen type I, dentin sialophosphoprotein (DSPP), and dentin matrix
      protein 1. The gene expressions were verified using ALP activity assessment,
      immunocytochemistry staining of osteocalcin and DSPP, and mineralization assay
      using alizarin red S stain. RESULTS: All BG extractions up-regulated the
      expression of odontogenic genes, and the most significant enhancement was in the
      nano-58S BG group. All BG extractions, especially nano-58S, increased ALP
      activity, osteocalcin and DSPP protein production, and mineralized nodules
      formation. CONCLUSIONS: Compared with regular BG, the novel nano-58S BG can
      induce the differentiation and mineralization of hDPCs more efficiently and might
      be a better potential candidate for dentin-pulp complex regeneration.

PMID- 24331997
TI  - Proinflammatory cytokines induce stromelysin-1-mediated cell proliferation in
      dental pulp fibroblast-like cells.
AB  - INTRODUCTION: We previously showed that the stromelysin-1 (matrix
      metalloproteinase 3) may have a putative role in dental pulp wound healing.
      However, its mechanism of action in wound repair has not been characterized. This
      study used stromelysin small interfering RNA transfected into rat dental pulp
      fibroblast-like cells (DPFCs) to investigate whether stromelysin-1 activity is
      induced by cytokines (interleukin-1 beta, tumor necrosis factor alpha, and
      interferon gamma) and/or is associated with cell proliferation and apoptosis.
      METHODS: We used reverse-transcription polymerase chain reaction, Western
      blotting, stromelysin-1 activity, WST-1 proliferation, and DNA fragmentation
      enzyme-linked immunosorbent assays to evaluate the siRNA-mediated down-regulation
      of stromelysin-1 expression and activity and changes in the
      proliferative/apoptotic responses associated with this reduced expression.
      RESULTS: Low concentrations of proinflammatory cytokines induced the expression
      of stromelysin-1 messenger RNA and protein and increased stromelysin-1 activity
      and cell proliferation, but they had no effect on apoptosis. When stromelysin-1
      expression was silenced using stromelysin-1 siRNA, we noted a potent and
      significant suppression of cytokine-induced stromelysin-1 expression and
      activity, decreased cell proliferation, and increased apoptosis. Finally,
      exogenous stromelysin-1 was found to induce cell proliferation in DPFCs.
      CONCLUSIONS: Our results showed that proinflammatory cytokine-induced stromelysin
      1 regulates cell proliferation and anti-apoptosis in DPFCs in addition to their
      better documented destructive role in inflammation.

PMID- 24331999
TI  - The effect of octamer-binding transcription factor 4B1 on microRNA signals in
      human dental pulp cells with inflammatory response.
AB  - INTRODUCTION: Dental pulp surrounded by rigid dentin is vulnerable to
      inflammatory stress; because of this, the invaded bacteria could cause
      irreversible pulpitis and necrosis. Octamer-binding transcription factor 4B1 (Oct
      4B1), a newly discovered Oct-4 spliced variant belonging to the class V of the
      POU transcription factor family, serves as a precursor of Oct-4B and an essential
      functional isoform of Oct-4. However, its specific role in the inflammatory
      response of dental pulp cells (DPCs) remains unknown. METHODS: To explore the
      effect of Oct-4B1 on the inflammatory response of DPCs, messenger RNA expression
      of Oct-4B1 and Oct-4B in DPCs with lipopolysaccharide (LPS) induction was
      examined by real-time polymerase chain reaction. The expression of Oct-4B1 in
      DPCs was knocked down by specific small interfering RNA (siRNA); cell
      proliferation and the apoptosis rate were detected by the Cell Counting Kit-8
      (Tokyo, Dojindo, Japan) and Hoechst-propidium iodide staining. The microRNA
      (miRNA) expression profiles were examined by miRNA microarray and bioinformatic
      analysis. RESULTS: We showed the messenger RNA expression of Oct-4B1 and Oct-4B
      was up-regulated in DPCs with LPS stimulation, whereas the knockdown expression
      of Oct-4B1 led to down-regulation of Oct-4B and an increased number of apoptotic
      cells in DPCs with LPS stimulation. Moreover, a total of 38 miRNAs were
      differentially expressed (including 4 up-regulated and 34 down-regulated) in DPCs
      with Oct-4B1 knockdown. Six of them were confirmed by real-time polymerase chain
      reaction, among which the target genes of miR-221 were predicted to be enriched
      in 14 Kyoto Encyclopedia of Genes and Genomes pathways represented by mitogen
      activated protein kinase, Wnt, and Toll-like signaling pathways. CONCLUSIONS: Oct
      4B1 may play a critical role in the inflammatory response of DPCs through
      interaction with miRNAs.

PMID- 24331998
TI  - In vitro regulation of CCL3 and CXCL12 by bacterial by-products is dependent on
      site of origin of human oral fibroblasts.
AB  - INTRODUCTION: Production of chemokines by tissue resident cells is one of the
      main mechanisms involved in the inflammatory infiltrate formation during
      inflammation. The specific ability of fibroblasts from different oral tissues
      such as gingiva, periodontal ligament, and dental pulp from permanent and
      deciduous teeth in producing the chemokines CCL3 and CXCL12 under stimulation by
      bacterial products commonly found in endodontic infections was investigated.
      METHODS: Cultures of fibroblasts from gingiva and periodontal ligament as well as
      from dental pulp from permanent and deciduous teeth were established by using an
      explant technique and stimulated with increasing concentrations of Escherichia
      coli lipopolysaccharide (EcLPS) and Enterococcus faecalis lipoteichoic acid
      (EfLTA) for 1, 6, and 24 hours. Supernatants were tested for CCL3 and CXCL12 by
      enzyme-linked immunosorbent assay. RESULTS: In general, CCL3 production was
      induced by EcLPS in the 4 fibroblast subtypes and by EfLTA in fibroblasts from
      gingiva and periodontal ligament. Constitutive CXCL12 synthesis decreased in all
      fibroblast subtypes especially under stimulation with EcLPS. Fibroblast from
      permanent deciduous teeth was the cell type presenting the most expressive
      reduction in CXCL12 release by both stimuli. On the basis of computational
      matching of CXCL12 mRNA with the microRNAs miR-141 and miR-200a, their expression
      was also investigated. Although detected in the fibroblasts, these molecules
      remained unaltered by bacterial by-product stimulation. CONCLUSIONS: EcLPS and
      EfLTA induced the production of CCL3 and unbalanced the synthesis of CXCL12 in a
      manner dependent on the specific tissue origin of fibroblasts.

PMID- 24332000
TI  - Not all electronic foramen locators are accurate in teeth with enlarged apical
      foramina: an in vitro comparison of 5 brands.
AB  - INTRODUCTION: Electronic working length measurement during root canal treatment
      in teeth with enlarged apical foramina is a challenge. The aims of this in vitro
      study were (1) to assess the influence of foramen widening on the accuracy of 5
      different electronic foramen locators (EFLs) and (2) to compare the accuracy of
      EFLs in different foramen sizes. METHODS: The following EFLs were used: MiniApex,
      Root ZXII, iPex, Propex II, and Elements Apex Locator. Each EFL was used in 3
      groups (n = 20) of extracted teeth, with foramen diameters of 0.27 mm (G27), 0.47
      mm (G47), and 0.72 mm (G72). Working length was measured according to
      manufacturer's instructions and compared with visual measurements (control
      method). Results were classified as accurate (equal or differences <= 0.05 mm) or
      inaccurate (differences > 0.5 mm). RESULTS: In G27, all EFLs yielded accurate
      findings (intragroup reliability; Fisher exact test, P < .05), compared with only
      MiniApex, Root ZXII, and Elements Apex Locator in G47 and G72. MiniApex, Root
      ZXII, and Elements Apex Locator were similarly accurate regardless of foramen
      size. iPex and Propex II were the least accurate among the devices tested, and
      foramen diameter influenced their accuracy, with greater diameters yielding
      poorer EFL performance. CONCLUSIONS: Foramen diameter did not influence the
      accuracy of MiniApex, Root ZXII, and Elements Apex Locator EFLs. iPex and Propex
      II showed decreased accuracy as foramen size increased.

PMID- 24332001
TI  - Effects of ProRoot MTA, Bioaggregate, and Micromega MTA on odontoblastic
      differentiation in human dental pulp cells.
AB  - INTRODUCTION: The aim of this study was to compare the biocompatibility and
      odontogenic potential of newly developed Bioaggregate (BA) and Micromega MTA
      (MMTA) with ProRoot MTA (PMTA) and intermediate restorative material (IRM) by
      using human dental pulp cells. METHODS: Biocompatibility was assessed by an 3
      (4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide assay and scanning
      electron microscopy. Differentiation was evaluated by alkaline phosphatase (ALP)
      activity, alizarin red staining, and reverse transcriptase-polymerase chain
      reaction for the maker genes. The levels of inflammatory mediators and cytokines
      were measured by reverse transcriptase-polymerase chain reaction and enzyme
      linked immunosorbent assay. RESULTS: PMTA, BA, and MMTA exhibited equally good
      biocompatibility, whereas IRM showed cytotoxicity compared with these materials.
      PMTA, BA, and MMTA increased the ALP activity, promoted mineralization nodule
      formation, and enhanced the mRNA expression level of the osteogenic/odontogenic
      markers (ALP, osteopontin, osteocalcin, dentin sialophosphoprotein, and dentin
      matrix protein-1) compared with IRM. The levels of proinflammatory mediators and
      proinflammatory cytokines were lower in PMTA, BA, and MMTA compared with the IRM
      group. CONCLUSIONS: Collectively, the biocompatibility, odontogenic potentials,
      and inflammatory response of BA and MMTA are equal to those of PMTA and superior
      to those of IRM.

PMID- 24332002
TI  - Influence of ferrule, post system, and length on biomechanical behavior of
      endodontically treated anterior teeth.
AB  - INTRODUCTION: The aim of this study was to evaluate the influence of post system,
      length, and ferrule on biomechanical behavior of endodontically treated anterior
      teeth. METHODS: The investigation was conducted by using laboratory tests and 3
      dimensional finite element analysis. Eighty bovine incisors were selected and
      divided into 8 treatment groups (n = 10) with absence of ferrule and 2.0 mm of
      ferrule, restored with glass fiber post or cast post and core, and 12.0 and 7.0
      mm of post length. The specimens were loaded at 135 degrees  angle, and the
      strain was measured by using strain gauge method. Specimens were subsequently
      loaded until fracture. Strain and fracture resistance results were analyzed by 3
      way analysis of variance and Tukey honestly significant difference tests (alpha =
      0.05). Three-dimensional models of a maxillary central incisor were generated
      with the same treatment variations used in laboratory tests. Each model was
      subjected to 100 N oblique loads. Results were evaluated by von Mises criterion.
      RESULTS: Ferrule was a determining factor in the strain, fracture resistance, and
      fracture pattern. In the absence of ferrule, the use of fiberglass posts
      represents a conservative choice from the standpoint of the fracture patterns
      observed. The length of 7 mm for cast post and cores produced high rates of root
      fractures. Finite element analysis showed that glass fiber post showed
      homogeneous stress distribution, whereas cast post showed stress concentration
      into root canal. CONCLUSIONS: Post length influenced only the cast post strain
      and stress distribution. The ferrule groups always showed more satisfactory
      stress distribution and fracture resistance.

PMID- 24332003
TI  - Cytotoxicity evaluation of a new resin-based hybrid root canal sealer: an in
      vitro study.
AB  - OBJECTIVE: This study evaluated the cytotoxicity of the new experimental self
      adhesive, methachrylate-based hybrid root canal sealer XT and compared it with
      the epoxy resin-based AH Plus Jet. METHODS: The cytotoxicity of the tested
      materials was evaluated after 1, 24, 48, and 72 hours by using growing and
      confluent mouse fibroblast cell line L929. L929 fibroblasts were maintained in
      Dulbecco modified medium containing 10% fetal calf serum at 37 degrees C and 5%
      CO2. At confluence, cells were seeded in 24-well plates at concentration of 1.5 *
      10(5) cells (growing cells) or 2.5 * 10(5) (confluent cells) for each well. An
      amount of 5 MUL of each root sealer (mixed according to manufacturer's
      specifications) was placed into individual wells containing a monolayer of L929
      cells to mimic the in vivo condition of the possible extrusion of sealer in the
      periapical tissues. Neutral Red and [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl
      tetrazolium bromide] were used for the cytotoxicity evaluation. Untreated cells
      were used as control. Two-way analysis of variance with Bonferroni test was used
      to compare the toxicity of the 2 sealers; one-way analysis of variance with Tukey
      test was performed to compare the cytotoxicity of each sealer at any considered
      time points (P < .05). Results were confirmed by examination with optical
      microscope. RESULTS: Both sealers induced a time-dependent cell death of mouse
      fibroblast L929; however, XT was less cytotoxic than AH Plus Jet as indicated by
      viability and morphologic analyses, and its initial cytotoxicity decreased
      progressively over time. CONCLUSIONS: These data support the possible use of XT
      as an endodontic sealer.

PMID- 24332004
TI  - Morphology and microhardness of dentin at the furcation area of mandibular
      molars.
AB  - INTRODUCTION: This study evaluated dentin morphology and microhardness at the
      furcation area of mandibular molars. METHODS: Tooth segments of mandibular molars
      were embedded in resin blocks and bisected longitudinally (n = 20), and the
      furcation area was delimited by tracing 2 orthogonal lines from the most concave
      point of the outer surface of the furcation toward the mesial and distal canal
      entrances. In half of the specimens, Knoop microhardness was measured in 2
      directions in the furcation area: vertically, parallel to the orthogonal lines
      and the bisector of the angle formed by them; and horizontally, in the outer
      (close to the pulp chamber floor), inner (close to the cementum), and middle
      dentin layers. Data were analyzed statistically by one-way analysis of variance
      and Tukey-Kramer test (alpha = 0.05). The other half of the specimens were
      examined by scanning electron microscopy to evaluate dentin morphology and
      trajectory of the tubules. RESULTS: No statistically significant difference (P >
      .05) was found among the mesial (46.5 +/- 6.4), central (47.3 +/- 8.1), and
      distal (49.7 +/- 6.5) orthogonal lines. The inner dentin layer (51.7 +/- 2.5) was
      statistically similar to the middle (46.3 +/- 2.9) (P > .05), which was similar
      to the outer layer (41.4 +/- 2.4) (P > .05). The inner layer was significantly
      harder than the outer layer (P < .05). The morphologic analysis revealed a
      tendency of calcification of the tubules from the outer toward the inner layer.
      CONCLUSIONS: Dentin microhardness at the furcation area is uniform in its 3
      vertical axes, but the inner dentin layer is harder than the outer layer. The
      dentinal tubules follow a centripetal direction toward the inner layer, in which
      dentin is much more mineralized.

PMID- 24332005
TI  - Histologic study of a human immature permanent premolar with chronic apical
      abscess after revascularization/revitalization.
AB  - INTRODUCTION: Histologic studies of teeth from animal models of
      revascularization/revitalization are available; however, specimens from human
      studies are lacking. The nature of tissues formed in the canal of human
      revascularized/revitalized teeth was not well established. METHODS: An immature
      mandibular premolar with infected necrotic pulp and a chronic apical abscess was
      treated with revascularization/revitalization procedures. At both the 18-month
      and 2-year follow-up visits, radiographic examination showed complete resolution
      of the periapical lesion, narrowing of the root apex without root lengthening,
      and minimal thickening of the canal walls. The revascularized/revitalized tooth
      was removed because of orthodontic treatment and processed for histologic
      examination. RESULTS: The large canal space of revascularized/revitalized tooth
      was not empty and filled with fibrous connective tissue. The apical closure was
      caused by cementum deposition without dentin. Some cementum-like tissue was
      formed on the canal dentin walls. Inflammatory cells were observed in the coronal
      and middle third of revascularized/revitalized tissue. CONCLUSIONS: In the
      present case, the tissue formed in the canal of a human
      revascularized/revitalized tooth was soft connective tissue similar to that in
      the periodontal ligament and cementum-like or bone-like hard tissue, which is
      comparable with the histology observed in the canals of teeth from animal models
      of revascularization/revitalization.

PMID- 24332006
TI  - Treatment of a hypertaurodontic maxillary second molar in a patient with 10
      taurodonts: a case report.
AB  - INTRODUCTION: Taurodontism is an aberration in tooth morphology characterized by
      vertically enlarged pulp chambers, apical displacement of pulp floors, and short
      roots. So far in the literature, no more than 8 taurodonts have been reported in
      1 patient. The aim of this case report was to describe the endodontic management
      of a hypertaurodont maxillary second molar and to present a rare case with 10
      taurodonts in a black man with a biometric analysis using cone-beam computed
      tomographic imaging. METHODS: An 18 year-old black man was referred to the
      postgraduate endodontic clinic for emergency treatment. The patient's medical
      history was noncontributory. Tooth #2 had lingering pain in response to the cold
      test and was positive to both percussion and palpation. Radiographic examination
      showed the characteristics of taurodontism and periapical radiolucency around the
      root apices of tooth #2. Tooth #2 was diagnosed with symptomatic irreversible
      pulpitis and symptomatic apical periodontitis. The tooth was endodontically
      treated in 2 appointments. A panoramic radiograph showed multiple taurodontism.
      At the follow-up, a cone-beam computed tomographic scan was taken to further
      evaluate and diagnose taurodontism. Ten molars showed taurodontism including 7
      hypertaurodonts, 2 mesotaurodonts, and a hypotaurodont. High variations of root
      canal anatomy were observed among taurodonts including maxillary and mandibular
      hypertaurodonts with C-shape canals. CONCLUSIONS: The present case describes 10
      taurodonts in a patient with no specific syndromes and endodontic treatment of a
      hypertaurodont maxillary second molar. Cone-beam computed tomographic imaging may
      be useful in the evaluation and management of the anatomic complexity of roots
      and root canals of taurodonts.

PMID- 24332007
TI  - Coexistence of systemic lupus erythematosus and multiple sclerosis: prevalence,
      clinical characteristics, and natural history.
AB  - OBJECTIVES: The coexistence of systemic lupus erythematosus (SLE) and multiple
      sclerosis (MS) in the same individual has rarely been described. Our objective
      was to report on the prevalence, clinical characteristics, and prognosis of cases
      fulfilling the criteria for both SLE and MS. METHODS: We utilized existing
      patient cohorts from the Departments of Rheumatology and Neurology, University of
      Crete, and screened patients diagnosed with either SLE (n = 728) or MS (n = 819)
      for features of both diseases. The clinical, laboratory, and neuroimaging
      findings were assessed. RESULTS: We identified nine patients who fulfilled the
      diagnostic criteria for both SLE and MS, corresponding to a prevalence rate of
      1.0-1.2% in each cohort. All patients were women, with an average age at SLE
      diagnosis of 42.1 years (range: 34-56 years). The diagnosis of SLE preceded the
      development of MS in five patients, with a time lag <= 5 years in four of them.
      Initial presentation of MS included spinal symptoms in seven patients. All
      patients had features of mild SLE with predominantly cutaneous, mucosal, and
      musculoskeletal manifestations. Accordingly, therapeutic decisions were mainly
      guided by the severity of the neurological syndrome. During the median follow-up
      of 4 years (range: 1-10 years), three patients remained stable and the remaining
      experienced gradual deterioration in their neurological status. SLE remained
      quiescent in all patients while on standard immunomodulatory MS therapy.
      CONCLUSIONS: Occurrence of both diseases in the same individual is rare,
      corroborating data that suggest distinct molecular signatures. SLE and MS
      coexistence was not associated with a severe phenotype for either entity.

PMID- 24332008
TI  - Gout tophus detection-a comparison of dual-energy CT (DECT) and histology.
AB  - OBJECTIVES: To compare dual-energy CT images (DECT) directly with gold standard
      histology. METHODS: A 85-year-old woman with chronic recurrent gouty arthritis
      and macroscopically visible tophi was assessed with DECT-scans of her feet. When
      she died 7 days later, three tophi in different regions and in different tissues
      of her left foot were processed for histological examination. RESULTS: Of the
      selected tophi, two were almost completely missed by the color-coding DECT
      sequences. The tophi remained in most of their volume below the detection
      threshold value of 150HU (default value). CONCLUSIONS: It could be demonstrated
      that DECT only highlights the dense tophi (corresponding of approximately 15
      20vol% urate in the tophus). Less dense tophi, despite considerable size, will be
      missed in the color-coded images.

PMID- 24332009
TI  - Post-traumatic cyst-like lesion of the radius: a rare but benign lesion.

PMID- 24332010
TI  - Flow cytometric evaluation of sperm apoptosis in semen of silver foxes in the
      breeding period.
AB  - The objective of the study was to evaluate cytometrically the percentage of
      apoptotic and necrotic spermatozoa in fresh semen of silver foxes in the breeding
      season. In males F3 and F4 with high percentages of early apoptotic (A+Pi-), late
      apoptotic (A+Pi+) and necrotic (A-Pi+) spermatozoa as well as 56-65% of living
      spermatozoa (A-Pi-) with progressive motility, the semen was characterised by
      reduced fertility. In males F1 and F2 with spermatozoa showing the motility and
      viability of 89-90% and high percentages of living cells that do not bind Annexin
      V and propidium iodide, the semen was assessed as valuable and useful for
      artificial insemination. Amongst 16 females of group I and II inseminated with
      semen from F1 and F2 males, 15 (93.75%) had multi-cub litters - on average 6.1
      and 4.8, respectively. In contrast, amongst 16 females of group III and IV
      inseminated with semen from F3 and F4 males, only 10 (62.5%) had litters with few
      cubs (on average 2.6 in group III and 2.1 in group IV). Our findings explicitly
      indicate that semen of farm male foxes should be evaluated before the breeding
      season, as one of the causes of reproduction failures is likely to be a high
      percentage of apoptotic and necrotic spermatozoa. Thanks to flow cytometry, fresh
      ejaculates can be speedily evaluated and their usefulness for artificial
      insemination determined. 

PMID- 24332011
TI  - Postsurgical inflammatory neuropathy: a report of five cases.
AB  - BACKGROUND: Clinical and pathologic descriptions of postsurgical inflammatory
      neuropathy have been reported but this condition is still under recognized.
      METHODS: We reviewed 5 cases of a biopsy-proven inflammatory neuropathy that
      occurred within 30 days after surgical procedures. These patients were seen at
      one center in a 2-year period. RESULTS: All patients developed neuropathy
      symptoms with time delay between the surgery and the neuropathy onset. In all,
      the symptoms progressed up to the time of evaluation. Electrophysiological
      studies revealed mononeuropathy or asymmetrical polyneuropathy with active
      denervation. Nerve biopsies showed ischemic injury and perivascular inflammatory
      collections in all cases. All patients were treated with intravenous
      methylprednisolone and four of them showed clinical improvement. The non
      responsive patient did not receive immunotherapy until 2 years after neuropathy
      onset. CONCLUSIONS: The report illustrates that focal or asymmetrical neuropathy
      is typical of postsurgical inflammatory neuropathy and has a favorable outcome
      after intravenous corticosteroid treatment. The report underscores the importance
      for considering potentially treatable inflammatory neuropathies in the post
      surgical setting.

PMID- 24332013
TI  - Melanoma spheroid formation involves laminin-associated vasculogenic mimicry.
AB  - Melanoma is a tumor where virulence is conferred on transition from flat (radial)
      to three-dimensional (tumorigenic) growth. Virulence of tumorigenic growth is
      governed by numerous attributes, including presence of self-renewing stem-like
      cells and related formation of patterned networks associated with the melanoma
      mitogen, laminin, a phenomenon known as vasculogenic mimicry. Vasculogenic
      mimicry is posited to contribute to melanoma perfusion and nutrition in vivo; we
      hypothesized that it may also play a role in stem cell-driven spheroid formation
      in vitro. Using a model of melanoma in vitro tumorigenesis, laminin-associated
      networks developed in association with three-dimensional melanoma spheroids. Real
      time PCR analysis of laminin subunits showed that spheroids formed from anchorage
      independent melanoma cells expressed increased alpha4 and beta1 laminin chains
      and alpha4 laminin expression was confirmed by in situ hybridization. Association
      of laminin networks with melanoma stem cell-associated nestin and vascular
      endothelial growth factor receptor-1 also was documented. Moreover, knockdown of
      nestin gene expression impaired laminin expression and network formation within
      spheroids. Laminin networks were remarkably similar to those observed in melanoma
      xenografts in mice and to those seen in patient melanomas. These data indicate
      that vasculogenic mimicry-like laminin networks, in addition to their genesis in
      vivo, are integral to the extracellular architecture of melanoma spheroids in
      vitro, where they may serve as stimulatory scaffolds to support three-dimensional
      growth. 

PMID- 24332014
TI  - High activities of BACE1 in brains with mild cognitive impairment.
AB  - We recently discovered elevated beta-secretase 1 (BACE1) activity in brains with
      sporadic Alzheimer disease (AD). Moreover, we also found high levels of BACE1
      enzymatic activity in the cerebrospinal fluid from patients with both mild
      cognitive impairment (MCI) and AD. These results suggest that elevation of BACE1
      enzymatic activity may occur early or may contribute to AD. We therefore examined
      whether BACE1 enzymatic activity was changed in MCI brains. BACE1 activity and
      tumor necrosis factor (TNF)-alpha levels were measured by enzymatic assay and
      ELISA in the temporal cortex from 18 patients with clinically well-characterized
      AD, 18 patients with MCI, and 18 healthy controls. We found a significant
      increase in BACE1 activity and protein level in brains of MCI and AD patients.
      Moreover, increased BACE1 activity correlated with plaque numbers and cognition
      status. We also found an increase in TNF-alpha in MCI brains. In vitro study
      revealed that TNF-alpha rather than other cytokines can up-regulate BACE1 protein
      expression. These findings suggest that BACE1 increase occurs early in MCI and is
      possibly induced by TNF-alpha and that BACE1 enzymatic activity may be important
      for conversion of MCI to AD. 

PMID- 24332015
TI  - Phosphorylation of AKT and abdominal aortic aneurysm formation.
AB  - It is hypothesized that differential AKT phosphorylation between sexes is
      important in abdominal aortic aneurysm (AAA) formation. Male C57BL/6 mice
      undergoing elastase treatment showed a typical AAA phenotype (80% over baseline,
      P < 0.001) and significantly increased phosphorylated AKT-308 (p308) and total
      AKT (T-AKT) at day 14 compared with female mice. Elastase-treated Raw cells
      produced increased p308 and significant amounts of matrix metalloproteinase 9
      (MMP-9), and these effects were suppressed by LY294002 treatment, a known AKT
      inhibitor. Male and female rat aortic smooth muscle cells treated with elastase
      for 1, 6, or 24 hours demonstrated that the p308/T-AKT and AKT-Ser-473/T-AKT
      ratios peaked at 6 hours and were significantly higher in the elastase-treated
      cells compared with controls. Similarly, male cells had higher phosphorylated
      AKT/T-AKT levels than female cells. LY294002 also inhibited elastase-induced p308
      formation more in female smooth muscle cells than in males, and the corresponding
      cell media had less pro-MMP-9. AKT siRNA significantly decreased secretion of pro
      MMP-9, as well as pro-MMP-2 and active MMP-2 from elastase-treated male rat
      aortic smooth muscle cells. IHC of male mice AAA aortas showed increased p308,
      AKT-Ser-473, and T-AKT compared with female mice. Aortas from male AAA patients
      had a significantly higher p308/T-AKT ratio than female AAA tissues. These data
      suggest that AKT phosphorylation is important in the upstream regulation of MMP
      activity, and that differential phosphorylation may be important in sex
      differences in AAA. 

PMID- 24332016
TI  - Expression of the homeobox gene HOXA9 in ovarian cancer induces peritoneal
      macrophages to acquire an M2 tumor-promoting phenotype.
AB  - Tumor-associated macrophages (TAMs) exhibit an M2 macrophage phenotype that
      suppresses anti-tumor immune responses and often correlates with poor outcomes in
      patients with cancer. Patients with ovarian cancer frequently present with
      peritoneal carcinomatosis, but the mechanisms that induce naive peritoneal
      macrophages into TAMs are poorly understood. In this study, we found an increased
      abundance of TAMs in mouse i.p. xenograft models of ovarian cancer that expressed
      HOXA9, a homeobox gene that is associated with poor prognosis in patients with
      ovarian cancer. HOXA9 expression in ovarian cancer cells stimulated chemotaxis of
      peritoneal macrophages and induced macrophages to acquire TAM-like features.
      These features included induction of the M2 markers, CD163 and CD206, and the
      immunosuppressive cytokines, IL-10 and chemokine ligand 17, and down-regulation
      of the immunostimulatory cytokine, IL-12. HOXA9-mediated induction of TAMs was
      primarily due to the combinatorial effects of HOXA9-induced, tumor-derived
      transforming growth factor-beta2 and chemokine ligand 2 levels. High HOXA9
      expression in clinical specimens of ovarian cancer was strongly associated with
      increased abundance of TAMs and intratumoral T-regulatory cells and decreased
      abundance of CD8(+) tumor-infiltrating lymphocytes. Levels of immunosuppressive
      cytokines were also elevated in ascites fluid of patients with tumors that highly
      expressed HOXA9. HOXA9 may, therefore, stimulate ovarian cancer progression by
      promoting an immunosuppressive microenvironment via paracrine effects on
      peritoneal macrophages. 

PMID- 24332017
TI  - Central orchestration of peripheral nutrient partitioning and substrate
      utilization: implications for the metabolic syndrome.
AB  - Energy homoeostasis is maintained through a complex interplay of nutrient intake
      and energy expenditure. The central nervous system is an essential component of
      this regulation, as it integrates circulating signals of hunger and satiety to
      develop adaptive responses at the behavioural and metabolic levels, while the
      hypothalamus is regarded as a particularly crucial structure in the brain in
      terms of energy homoeostasis. The arcuate nucleus (ARC) of the hypothalamus
      contains at least two intermingled neuronal populations: the neurons that produce
      neuropeptide Y (NPY); and the Agouti-related protein (AgRP) produced by AgRP/NPY
      neurons situated below the third ventricle in close proximity to
      proopiomelanocortin (POMC)-producing neurons. POMC neurons exert their catabolic
      and anorectic actions by releasing alpha-melanocyte-stimulating hormone (alpha
      MSH), while AgRP neurons oppose this action by exerting tonic GABAergic
      inhibition of POMC neurons and releasing the melanocortin receptor inverse
      agonist AgRP. The release of neurotransmitters and neuropeptides by second-order
      AgRP neurons appears to take place on a multiple time scale, thereby allowing
      neuromodulation of preganglionic neuronal activity and subsequent control of
      nutrient partitioning - in other words, the coordinated regulation of conversion,
      storage and utilization of carbohydrates vs. lipids. This suggests that the
      function of AgRP neurons extends beyond the strict regulation of feeding to the
      regulation of efferent organ activity, such that AgRP neurons may now be viewed
      as an important bridge between central detection of nutrient availability and
      peripheral nutrient partitioning, thus providing a mechanistic link between
      obesity and obesity-related disorders. 

PMID- 24332019
TI  - [Visceral larva migrans with cardiac manifestation: a case report and literature
      review].
AB  - INTRODUCTION: Toxocariasis is a roundworm infection that may be associated with
      serious cardiac manifestations. We report one case and review another 12 cases in
      the literature. CASE REPORT: A 74-year-old man, presented with clinical features
      of myopericarditis. Eosinophil count was 20,000/mm(3). The ELISA and Western Blot
      were positive for Toxocara canis. The patient was treated with corticosteroids
      and antiparasite treatment. The outcome was rapidly favorable. DISCUSSION: In the
      other 12 cases, the cardiac manifestations were often severe: six myocarditis,
      three tamponades and three Loeffler's endocarditis have been published. Four
      therapeutic strategies have been reported: symptomatic treatment alone was
      associated with worse progressive; antiparasite treatment alone or companied with
      corticosteroids and corticosteroids alone had good results. CONCLUSION: The
      toxocariasis should be investigated systematically in case of eosinophilic
      cardiomyopathy. The treatment strategy is still controversial.

PMID- 24332020
TI  - Long term rectal function after high-dose prostatecancer radiotherapy: results
      from a prospective cohort study.
AB  - PURPOSE: To prospectively evaluate long-term late rectal bleeding (lrb) and
      faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer
      in the AIROPROS 0102 population, and to assess clinical/dosimetric risk factors.
      MATERIALS AND METHODS: Questionnaires of 515 patients with G0 baseline
      incontinence and bleeding scores (follow-up >=6 years) were analysed.
      Correlations between lrb/linc and many clinical and dosimetric parameters were
      investigated by univariate and multivariate logistic analyses. The correlation
      between lrb/linc and symptoms during the first 3 years after RT was also
      investigated. RESULTS: Of 515 patients lrb G1, G2 and G3 was found in 32 (6.1%),
      2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50
      (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2-G3 lrb events
      was significantly reduced compared to the first 3-years (1% vs 2.7%, p=0.016)
      >=G1 lrb was significantly associated with V75 Gy (OR=1.07). In multivariate
      analysis, >=G1 linc was associated with V40 Gy (OR=1.015), use of
      antihypertensive medication (OR=0.38), abdominal surgery before RT (OR=4.7),
      haemorrhoids (OR=2.6), and G2-G3 acute faecal incontinence (OR=4.4), a nomogram
      to predict the risk of long-term >=G1 linc was proposed. Importantly, the
      prevalence of >=G1 linc was significantly correlated with the mean incontinence
      score during the first 3 years after RT (OR=16.3). CONCLUSIONS: Long-term
      (median: 7 years) rectal symptoms are prevalently mild and strongly correlated
      with moderate/severe events occurring in the first 3 years after RT. Linc was
      associated with several risk factors.

PMID- 24332021
TI  - Developing a class solution for Prostate Stereotactic Ablative Body Radiotherapy
      (SABR) using Volumetric Modulated Arc Therapy (VMAT).
AB  - BACKGROUND AND PURPOSE: To develop a class solution for prostate Stereotactic
      Ablative Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT).
      MATERIALS AND METHODS: Seven datasets were used to compare plans using one 360
      degrees  arc (1FA), one 210 degrees  arc (1PA), two full arcs and two partial
      arcs. Subsequently using 1PA, fifteen datasets were compared using (i) 6mm CTV
      PTV margins, (ii) 8mm CTV-PTV margins and (iii) including the proximal SV within
      the CTV. Monaco 3.2 (Elekta) was used for planning with the Agility MLC system
      (Elekta). RESULTS: Highly conformal plans were produced using all four arc
      arrangements. Compared to 1FA, 1PA resulted in significantly reduced rectal
      doses, and monitor units and estimated delivery times were reduced in six of
      seven cases. Using 6mm CTV-PTV margins, planning constraints were met for all
      fifteen datasets. Using 8mm margins required relaxation of the uppermost bladder
      constraint in three cases to achieve adequate coverage, and, compared to 6mm
      margins, rectal and bladder doses significantly increased. Including the proximal
      SV required relaxation of the uppermost bladder and rectal constraints in two
      cases, and rectal and bladder doses significantly increased. CONCLUSIONS:
      Prostate SABR VMAT is optimal using 1PA. 6mm CTV-PTV margins, compatible with
      daily fiducial-based IGRT, are consistently feasible in terms of target
      objectives and OAR constraints.

PMID- 24332022
TI  - Gold seed fiducials in analysis of linear and rotational displacement of the
      prostate bed.
AB  - BACKGROUND AND PURPOSE: This study aimed to investigate the magnitude of
      interfraction prostate bed motion during radiotherapy using both the implanted
      gold seed fiducials and the soft tissue registration and to define reasonable
      planning target volume (PTV) margins for different localization methods. MATERIAL
      AND METHODS: Thirteen prostatectomized prostate cancer patients, after implanting
      four gold seed fiducials into their prostate bed, were imaged daily using a
      pretreatment cone-beam computed tomography (CBCT). Linear and the rotational
      prostate bed motion (PBM) was measured for 466 CBCTs. RESULTS: The linear PBM
      mean and standard deviation values in millimeters are 0.0 +/- 0.5, 0.7 +/- 2.1
      and 0.8 +/- 1.6 in the LR, SI and AP axes, respectively. In 20% of the fractions
      the rotation of the prostate bed in sagittal plane exceeds +/-6 degrees  and in
      5% it exceeds +/-10 degrees  from the position on the planning CT. In the
      transversal and coronal planes 1% and 2% of it exceeds +/-6 degrees . The PTV
      margins are 2.4, 6.5 and 6.6mm in the LR, SI and AP axes, respectively, if
      imaging is performed for the first three treatment fractions. CONCLUSION: The
      linear PBM is largest in the SI and AP axis, whereas the rotation is largest in
      the sagittal plane. Bone localization during the first three treatment fractions
      can reduce PTV margins by 52%, 18% and 10% in the LR, SI and AP axes,
      respectively, whereas in daily CBCT the use of the gold seed fiducials seems
      profitable.

PMID- 24332018
TI  - Ketoacidosis at diagnosis of type 1 diabetes in French children and adolescents.
AB  - OBJECTIVES: This study aimed to evaluate the frequency of diabetic ketoacidosis
      (DKA) and its associated factors at the diagnosis of type 1 diabetes (T1D) in
      French children and adolescents prior to launching a public-health campaign of
      information to prevent DKA. PATIENTS AND METHODS: Over a 1-year period, 1299
      youngsters (aged < 15 years) were diagnosed with T1D at 146 paediatric centres in
      all regions of France. Age, gender, duration of symptoms, patient's pathway to
      diagnosis, clinical and biological signs, and family history of T1D were
      collected for each newly diagnosed patient. DKA was defined as pH < 7.30 or
      bicarbonate < 15 mmol/L, and severe DKA as pH < 7.10 or bicarbonate < 5 mmol/L.
      RESULTS: At the time of diagnosis, 26% of the children were aged 0-5 years, 34%
      were 5-10 years and 40% were 10-15 years. The overall prevalence of DKA was 43.9%
      (0-5 years: 54.2%; 5-10 years: 43.4%; and 10-15 years: 37.1%) and 14.8% for
      severe DKA (0-5 years: 16.6%; 5-10 years: 14.4%; and 10-15 years: 13.9%; < 2
      years: 25.3%). Severe DKA was more frequent when the child was hospitalized at
      the family's behest (26.6%) than when referred by a general practitioner (7.6%)
      or paediatrician (5.1%; 30.6%, 53.7% and 9.2%, respectively, by patients' age
      group). The frequency of DKA decreased to 20.1% (severe DKA: 4.4%) in families
      with a history of T1D. Multivariate analysis showed that age, pathway to
      diagnosis, duration of polyuria/polydipsia (< 1 week) and family history of T1D
      were associated with the presence of DKA, while pathway to diagnosis and family
      history of T1D were associated with severe DKA. CONCLUSION: DKA at the time of
      T1D diagnosis in children and adolescents is frequent and often severe. Patients'
      age, pathway to hospitalization and family history of diabetes were the main
      factors associated with DKA. These data suggest that a public-health campaign to
      prevent DKA at diagnosis can help reduce the frequency of DKA and also provide
      baseline data for evaluating the efficacy of such a campaign.

PMID- 24332023
TI  - Risk factors for brain injury after carbon ion radiotherapy for skull base
      tumors.
AB  - BACKGROUND AND PURPOSE: This study aimed to determine the risk factors for
      radiation-induced brain injury (RIBI) after carbon ion radiotherapy (CIRT) for
      treating skull base tumors. MATERIALS AND METHODS: Between April 1997 and January
      2009, CIRT at a total dose of 48.0-60.8Gy equivalent (GyE) was administered in 16
      fractions to 47 patients with skull base tumors. Of these patients, 39 who were
      followed up with magnetic resonance imaging (MRI) for more than 24months were
      analyzed. RIBI was assessed according to the MRI findings based on the Late
      Effects of Normal Tissue-Subjective, Objective, Management, Analytic criteria;
      clinical symptoms were assessed according to the Radiation Therapy Oncology
      Group/European Organisation for Research and Treatment of Cancer tables. The
      correlations of clinical and dosimetric parameters with incidence of ?grade 2
      RIBI were retrospectively analyzed. RESULTS: The median follow-up period was
      67months. The 5-year actuarial likelihoods of ?grade 2 RIBI and ?grade 2 clinical
      symptoms were 24.5% and 7.0%, respectively. Multivariate analysis demonstrated
      that the brain volume receiving more than 50GyE (V50) was a significant risk
      factor for the development of ?grade 2 RIBI (p=0.004). CONCLUSION: V50 was a
      significant risk factor for ?grade 2 RIBI after CIRT using a 16-fraction regimen.

PMID- 24332024
TI  - cGAS dimerization entangles DNA recognition.
AB  - Detection of foreign DNA in the cell cytosol triggers potent antiviral responses.
      In this issue of Immunity, Li et al. (2013) provide new structural and
      biochemical data indicating that a cytosolic DNA sensor, cyclic GMP-AMP synthase
      (cGAS), is activated by DNA-induced dimerization.

PMID- 24332025
TI  - A long-playing CD about the gammadelta TCR repertoire.
AB  - In this issue of Immunity, a study by Luoma et al. (2013) provides structural
      evidence for direct interactions of human Vdelta1(+) T cell receptors with CD1d,
      capping a long trail of evidence that CD1 might be a major influence on
      gammadelta T cell biology.

PMID- 24332026
TI  - Salmonella's masterful skill in mast cell suppression.
AB  - Salmonella bacteria often cause food-borne diseases. In this issue of Immunity,
      Choi et al. (2013) demonstrate that the Salmonella Typhimurium-secreted protein
      tyrosine phosphatase, SptP, suppresses mast cell degranulation, which enables
      bacterial dissemination.

PMID- 24332027
TI  - Making sense of HIV innate sensing.
AB  - Innate sensing of HIV is important in host control and pathogenesis. In this
      issue of Immunity, Lahaye et al. (2013) demonstrate that HIV capsid-cyclophilin A
      interactions affect viral cDNA sensing by the DNA sensor cCAS and contribute to
      differential pathogenesis of HIV-1 and HIV-2.

PMID- 24332028
TI  - New twist on an ancient innate immune pathway.
AB  - Activation of the complement system has long been known to be regulated by a
      series of steps involving fluid-phase convertases. In this issue of Immunity,
      Liszewski et al. (2013) report the discovery of an intracellular cathepsin-L
      dependent C3 activation pathway.

PMID- 24332030
TI  - Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced
      oligomerization.
AB  - Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate
      antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic
      dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation of
      TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the
      transcription of the IFN-beta gene. The structure of mouse cGAS bound to an 18 bp
      dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming
      a 2:2 complex. Enzyme assays and IFN-beta reporter assays of cGAS mutants
      demonstrated that interactions at both DNA binding sites are essential for cGAS
      activation. Mutagenesis and DNA binding studies showed that the two sites bind
      dsDNA cooperatively and that site B plays a critical role in DNA binding. The
      structure of mouse cGAS bound to dsDNA and 2',5' cGAMP provided insight into the
      catalytic mechanism of cGAS. These results demonstrated that cGAS is activated by
      dsDNA-induced oligomerization.

PMID- 24332029
TI  - The interleukin-1 family: back to the future.
AB  - Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation.
      The IL-1 family includes seven ligands with agonist activity (IL-1alpha and IL
      1beta, IL-18, IL-33, IL-36alpha, IL-36beta, IL-36gamma), three receptor
      antagonists (IL-1Ra, IL-36Ra, IL-38), and an anti-inflammatory cytokine (IL-37).
      Members of the IL-1 Receptor (IL-1R) family include six receptor chains forming
      four signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP), and two
      negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor
      antagonists, decoy receptors, and signaling inhibitors ensures a balance between
      amplification of innate immunity and uncontrolled inflammation. All cells of the
      innate immune system express and/or are affected by IL-1 family members.
      Moreover, IL-1 family members play a key role in the differentiation and function
      of polarized innate and adaptive lymphoid cells. Here we will review the key
      properties of IL-1 family members, with emphasis on pathways of negative
      regulation and orchestration of innate and adaptive immunity. 

PMID- 24332032
TI  - A Shigella effector dampens inflammation by regulating epithelial release of
      danger signal ATP through production of the lipid mediator PtdIns5P.
AB  - Upon infection with Shigella flexneri, epithelial cells release ATP through
      connexin hemichannels. However, the pathophysiological consequence and the
      regulation of this process are unclear. Here we showed that in intestinal
      epithelial cell ATP release was an early alert response to infection with enteric
      pathogens that eventually promoted inflammation of the gut. Shigella evolved to
      escape this inflammatory reaction by its type III secretion effector IpgD, which
      blocked hemichannels via the production of the lipid PtdIns5P. Infection with an
      ipgD mutant resulted in rapid hemichannel-dependent accumulation of extracellular
      ATP in vitro and in vivo, which preceded the onset of inflammation. At later
      stages of infection, ipgD-deficient Shigella caused strong intestinal
      inflammation owing to extracellular ATP. We therefore describe a new paradigm of
      host-pathogen interaction based on endogenous danger signaling and identify
      extracellular ATP as key regulator of mucosal inflammation during infection. Our
      data provide new angles of attack for the development of anti-inflammatory
      molecules.

PMID- 24332031
TI  - Salmonella typhimurium impedes innate immunity with a mast-cell-suppressing
      protein tyrosine phosphatase, SptP.
AB  - The virulence of Salmonella is linked to its invasive capacity and suppression of
      adaptive immunity. This does not explain, however, the rapid dissemination of the
      pathogen after it breaches the gut. In our study, S. Typhimurium suppressed
      degranulation of local mast cells (MCs), resulting in limited neutrophil
      recruitment and restricting outflow of vascular contents into infection sites,
      thus facilitating bacterial spread. MC suppression was mediated by secreted
      effector protein (SptP), which shares structural homology with Yersinia YopH.
      SptP functioned by dephosphorylating the vesicle fusion protein N-ethylmalemide
      sensitive factor and by blocking phosphorylation of Syk. Without SptP, orally
      challenged S. Typhimurium failed to suppress MC degranulation and exhibited
      limited colonization of the mesenteric lymph nodes. Administration of SptP to
      sites of E. coli infection markedly enhanced its virulence. Thus, SptP-mediated
      inactivation of local MCs is a powerful mechanism utilized by S. Typhimurium to
      impede early innate immunity. 

PMID- 24332034
TI  - S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of
      complement factor C3.
AB  - Psoriasis is a common heterogeneous inflammatory skin disease with a complex
      pathophysiology and limited treatment options. Here we performed proteomic
      analyses of human psoriatic epidermis and found S100A8-S100A9, also called
      calprotectin, as the most upregulated proteins, followed by the complement
      component C3. Both S100A8-S100A9 and C3 are specifically expressed in lesional
      psoriatic skin. S100A9 is shown here to function as a chromatin component
      modulating C3 expression in mouse and human cells by binding to a region upstream
      of the C3 start site. When S100A9 was genetically deleted in mouse models of skin
      inflammation, the psoriasis-like skin disease and inflammation were strongly
      attenuated, with a mild immune infiltrate and decreased amounts of C3. In
      addition, inhibition of C3 in the mouse model strongly reduced the inflammatory
      skin disease. Thus, S100A8-S100A9 can regulate C3 at the nuclear level and
      present potential new therapeutic targets for psoriasis. 

PMID- 24332033
TI  - Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes
      allergic inflammation.
AB  - Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic
      stem cells (HSCs) into effector cells that occurs in compartments outside of the
      bone marrow. Previous studies linked pattern-recognition receptor (PRR)
      expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether
      EMH operates in broader immune contexts remains unknown. Here, we demonstrate a
      previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting
      the population expansion of progenitor cells in the periphery and identify that
      TSLP-elicited progenitors differentiated into effector cells including
      macrophages, dendritic cells, and granulocytes and that these cells contributed
      to type 2 cytokine responses. The frequency of circulating progenitor cells was
      also increased in allergic patients with a gain-of-function polymorphism in TSLP,
      suggesting the TSLP-EMH pathway might operate in human disease. These data
      identify that TSLP-induced EMH contributes to the development of allergic
      inflammation and indicate that EMH is a conserved mechanism of innate immunity. 

PMID- 24332035
TI  - Location, location, location: macrophage positioning within tumors determines pro
      or antitumor activity.
AB  - Macrophages infiltrate hypoxic tumor regions, where they promote angiogenesis and
      immunosuppression. In this issue of Cancer Cell, Casazza and colleagues report
      that tumor-associated macrophage (TAM) entry into avascular tumor areas is
      regulated by Semaphorin 3A/Neuropilin-1 signaling; interference with this pathway
      entraps TAMs in oxygenated areas, preventing their tumorigenic function. 

PMID- 24332036
TI  - RAS and ROS in rhabdomyosarcoma.
AB  - The 5-year survival for localized rhabdomyosarcoma is over 70%, but only 30% for
      patients presenting with metastatic disease. In this issue of Cancer Cell, Chen
      and colleagues performed whole-genome and RNA sequencing on human
      rhabdomyosarcoma and identified RAS mutations and oxidative stress as potential
      therapeutic targets for high-risk embryonal rhabdomyosarcoma. 

PMID- 24332037
TI  - A novel bullet hits the proteasome.
AB  - An elegant paper by Anchoori and colleagues in this issue of Cancer Cell
      describes an irreversible inhibitor of Rpn13, one of the ubiquitin receptors on
      the 26S proteasome that is nonessential for proteasome function in most normal
      tissues, but is overexpressed in many solid tumors. 

PMID- 24332038
TI  - The evolution of tumor classification: a role for genomics?
AB  - Lung cancers are divided into four types according to their histologic
      appearance. Therapeutic decisions are partly based on histology. A recent study
      indicates that certain molecular alterations associate with histology and that
      therapies directed to these molecular changes improve outcome, indicating that
      genomic information should be incorporated into future tumor classification. 

PMID- 24332039
TI  - Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling
      blockade inhibits angiogenesis and restores antitumor immunity.
AB  - Recruitment of tumor-associated macrophages (TAMs) into avascular areas sustains
      tumor progression; however, the underlying guidance mechanisms are unknown. Here,
      we report that hypoxia-induced Semaphorin 3A (Sema3A) acts as an attractant for
      TAMs by triggering vascular endothelial growth factor receptor 1 phosphorylation
      through the associated holoreceptor, composed of Neuropilin-1 (Nrp1) and
      PlexinA1/PlexinA4. Importantly, whereas Nrp1 levels are downregulated in the
      hypoxic environment, Sema3A continues to regulate TAMs in an Nrp1-independent
      manner by eliciting PlexinA1/PlexinA4-mediated stop signals, which retain them
      inside the hypoxic niche. Consistently, gene deletion of Nrp1 in macrophages
      favors TAMs' entrapment in normoxic tumor regions, which abates their pro
      angiogenic and immunosuppressive functions, hence inhibiting tumor growth and
      metastasis. This study shows that TAMs' heterogeneity depends on their
      localization, which is tightly controlled by Sema3A/Nrp1 signaling. 

PMID- 24332040
TI  - Targeting oxidative stress in embryonal rhabdomyosarcoma.
AB  - Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of
      developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes,
      embryonal and alveolar, each with distinct clinical, molecular, and genetic
      features. Genomic analysis shows that embryonal tumors have more structural and
      copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are
      significantly associated with intermediate- and high-risk embryonal
      rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have
      fewer genetic lesions overall and no known recurrently mutated cancer consensus
      genes. To identify therapeutics for ERMS, we developed and characterized
      orthotopic xenografts of tumors that were sequenced in our study. High-throughput
      screening of primary cultures derived from those xenografts identified oxidative
      stress as a pathway of therapeutic relevance for ERMS. 

PMID- 24332041
TI  - NCOA5 haploinsufficiency results in glucose intolerance and subsequent
      hepatocellular carcinoma.
AB  - Type 2 diabetes (T2D) and male gender are associated with hepatocellular
      carcinoma (HCC) development. We demonstrate that heterozygous deletion of the
      Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor
      development is preceded by increased interleukin-6 (IL-6) expression, early-onset
      glucose intolerance, and progressive steatosis and dysplasia in livers.
      Blockading IL-6 overexpression averts glucose intolerance and partially deters
      HCC development. Moreover, reduced NCOA5 expression is associated with a fraction
      of human HCCs and HCCs with comorbid T2D. These findings suggest that NCOA5 is a
      haploinsufficient tumor suppressor and that NCOA5 deficiency increases
      susceptibility to both glucose intolerance and HCC, partially by increasing IL-6
      expression. Thus, our findings open additional avenues for developing therapeutic
      approaches to combat these diseases. 

PMID- 24332042
TI  - SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer
      and is often linked to loss of chromosome 3p, which harbors the VHL tumor
      suppressor gene, loss of chromosome 14q, which includes HIF1A, and gain of
      chromosome 5q. The relevant target(s) on chromosome 5q is not known. Here, we
      show that 5q amplification leads to overexpression of the SQSTM1 oncogene in
      ccRCC lines and tumors. Overexpression of SQSTM1 in ccRCC lines promoted
      resistance to redox stress and increased soft agar growth, while downregulation
      of SQSTM1 decreased resistance to redox stress, impaired cellular fitness, and
      decreased tumor formation. Therefore, the selection pressure to amplify 5q in
      ccRCC is driven, at least partly, by SQSTM1. 

PMID- 24332043
TI  - Transformation of the fallopian tube secretory epithelium leads to high-grade
      serous ovarian cancer in Brca;Tp53;Pten models.
AB  - High-grade serous ovarian carcinoma presents significant clinical and therapeutic
      challenges. Although the traditional model of carcinogenesis has focused on the
      ovary as a tumor initiation site, recent studies suggest that there may be
      additional sites of origin outside the ovary, namely the secretory cells of the
      fallopian tube. Our study demonstrates that high-grade serous tumors can
      originate in fallopian tubal secretory epithelial cells and also establishes
      serous tubal intraepithelial carcinoma as the precursor lesion to high-grade
      serous ovarian and peritoneal carcinomas in animal models targeting the Brca,
      Tp53, and Pten genes. These findings offer an avenue to address clinically
      important questions that are critical for cancer prevention and early detection
      in women carrying BRCA1 and BRCA2 mutations. 

PMID- 24332044
TI  - Discovery and characterization of super-enhancer-associated dependencies in
      diffuse large B cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is a biologically heterogeneous and
      clinically aggressive disease. Here, we explore the role of bromodomain and extra
      terminal domain (BET) proteins in DLBCL, using integrative chemical genetics and
      functional epigenomics. We observe highly asymmetric loading of bromodomain 4
      (BRD4) at enhancers, with approximately 33% of all BRD4 localizing to enhancers
      at 1.6% of occupied genes. These super-enhancers prove particularly sensitive to
      bromodomain inhibition, explaining the selective effect of BET inhibitors on
      oncogenic and lineage-specific transcriptional circuits. Functional study of
      genes marked by super-enhancers identifies DLBCLs dependent on OCA-B and suggests
      a strategy for discovering unrecognized cancer dependencies. Translational
      studies performed on a comprehensive panel of DLBCLs establish a therapeutic
      rationale for evaluating BET inhibitors in this disease. 

PMID- 24332045
TI  - A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1
      as a therapy for cancer.
AB  - The bis-benzylidine piperidone RA190 covalently binds to cysteine 88 of ubiquitin
      receptor RPN13 in the 19S regulatory particle and inhibits proteasome function,
      triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma
      (MM) lines, even those resistant to bortezomib, were sensitive to RA190 via
      endoplasmic reticulum stress-related apoptosis. RA190 stabilized targets of human
      papillomavirus (HPV) E6 oncoprotein, and preferentially killed HPV-transformed
      cells. After oral or intraperitoneal dosing of mice, RA190 distributed to plasma
      and major organs except the brain and inhibited proteasome function in skin and
      muscle. RA190 administration profoundly reduced growth of MM and ovarian cancer
      xenografts, and oral RA190 treatment retarded HPV16(+) syngeneic mouse tumor
      growth, without affecting spontaneous HPV-specific CD8(+) T cell responses,
      suggesting its therapeutic potential.

PMID- 24332047
TI  - Stress hormones in obstructive sleep apnea complications: the role of cortisol.

PMID- 24332046
TI  - Valid measures of periodic leg movements (PLMs) during a suggested immobilization
      test using the PAM-RL leg activity monitors require adjusting detection
      parameters for noise and signal in each recording.
AB  - OBJECTIVE AND BACKGROUND: Individuals with restless legs syndrome (RLS) (Willis
      Ekbom disease [WED]) usually have periodic leg movements (PLMs). The suggested
      immobilization test (SIT) measures sensory and motor features of WED during
      wakefulness. Surface electromyogram (EMG) recordings of the anterior tibialis
      (AT) are used as the standard for counting PLMs. However, due to several
      limitations, leg activity meters such as the PAM-RL were advanced as a potential
      substitute. In our study, we assessed the validity of the measurements of PLM
      during wakefulness (PLMW) in the SIT for PAM-RL using both default and custom
      detection threshold parameters compared to AT EMG. METHODS: Data were obtained
      from 39 participants who were diagnosed with primary WED and who were on stable
      medication as part of another study using the SIT to repeatedly evaluate WED
      symptoms over 6-12 months. EMG recordings and PAM-RL, when available, were used
      to detect PLMW for each SIT. Complete PAM-RL and polysomnography (PSG) EMG data
      were available for 253 SITs from that study. The default PAM-RL (dPAM-RL)
      detected leg movements based on manufacturer's noise (resting) and signal
      (movement) amplitude criteria developed to accurately detect PLM during sleep
      (PLMS). The custom PAM-RL (cPAM-RL) similarly detected leg movements except the
      noise and movement detection parameters were adjusted to match the PAM-RL data
      for each SIT. RESULTS: The distributions of the differences between either dPAM
      RL or cPAM-RL and EMG PLMW were strongly leptokurtic (Kurtosis >2) with many
      small differences and a few unusually large differences. These distributions are
      better described by median and quartile ranges than mean and standard deviation.
      Despite an adequate correlation (r=0.66) between the dPAM-RL and EMG recordings,
      the dPAM-RL on average significantly underscored the number of PLMW (median:
      quartiles=-13: -51.2, 0.0) and on Bland-Altman plots had a significant magnitude
      bias with greater underscoring for larger average PLMW/h. There also was an
      adequate correlation (r=0.70) between cPAM-RL and EMG but with minimal
      underscoring of PLMW (median quartiles=0.0; -20, 10) and no significant magnitude
      bias. Two scorers independently scoring 13% of the SITs showed an adequate
      interscorer reliability of 0.96-0.98. CONCLUSIONS: Our study confirms our
      expectation that measuring PLMW in a SIT using dPAM-RL is not valid and that
      adjustments to the detection threshold criteria are required. The PAM-RL, using
      parameters customized for each SIT provided a valid and reliable measure of PLMW
      with minimal magnitude bias compared to the AT EMG recordings.

PMID- 24332048
TI  - [Progress in three-dimensional cell culture techniques and its application in
      bone tumor research].

PMID- 24332049
TI  - [miR-216b suppresses cell proliferation and invasion by targeting PKCalpha in
      nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To elucidate whether miR-216b suppresses cell proliferation and
      invasion by targeting PKCalpha, thus to reveal the molecular mechanism that miR
      216b functions as a tumor suppressor in nasopharyngeal carcinoma (NPC). METHODS:
      PKCalpha 3'UTR-luciferase vector was constructed and dual-luciferase reporter
      gene assay was employed to examine the effect of miR-216b on luciferase activity.
      Nasopharyngeal cancer CNE2 cells were transfected with miR-216b mimics, and then
      qRT-PCR and Western blotting were performed to detect the expressions of PKCa
      mRNA and protein. The effects of PKCalpha downregulation on cell proliferation
      and invasion were assessed after PKCalpha siRNA were transfected into CNE2 cells.
      CNE2 cells were cotransfected with miR-216b mimics and PKCalpha plasmid, and the
      proliferation of CNE2 cells was assayed using a MTS cell proliferation assay kit.
      RESULTS: The results of dual-luciferase reporter gene assay demonstrated that miR
      216b could bind to the 3'-untranslated region (UTR) of PKCalpha and inhibited the
      luciferase activity to 62.4% of that of the mimics control cells. The expressions
      of PKCalpha mRNA and protein were significantly down-regulated by 49.1% and
      55.7%, respectively, in comparison with that of the control cells. siRNA-mediated
      downregulation of PKCalpha suppressed the proliferation and invasion ability of
      CNE2 cells, and could partially mimic the tumor-inhibiting effect of miR-216b.
      Moreover, the overexpressed PKCalpha may partially reverse the inhibitory effect
      of miR-216b on proliferation of CNE2 cells. CONCLUSION: miR-216b suppresses cell
      proliferation and invasion by targeting PKCalpha in NPC cells.

PMID- 24332050
TI  - [Effect of doxorubicin on TRAIL resistance and TRAIL receptor expression in
      lymphoma cell line SNK-6 cells].
AB  - OBJECTIVE: To investigate the effect of doxorubicin on TRAIL resistance and TRAIL
      receptor expression in lymphoma cell line SNK-6 cells. METHODS: SNK-6 cells
      treated with doxorubicin at different concentrations alone or in combination with
      tumor necrosis factor related apoptosis inducing ligand (TRAIL). Cell
      proliferation was evaluated by MTT assay. Apoptosis and the expression of TRAIL
      receptors were determined by flow cytometry. RESULTS: MTT assay showed that
      treatment with 100 and 1000 ng/ml doxorubicin for 24 h, the survival rates of SNK
      6 cells were (80.9 +/- 7.2)% and (53.7 +/- 2.8)%, significantly higher than that
      by treatment combined with 500 ng/ml TRAIL (64.9 +/- 1.1)% and (34.0 +/- 3.9)%,
      respectively (P < 0.05). Flow cytometry showed that after treatment with 100 and
      1000 ng/ml doxorubicin for 48 h, the survival rates of SNK-6 cells were (69.9 +/-
      6.1)% and (31.1 +/- 1.9)%, while treated in combination with 500 ng/ml TRAIL, the
      cell survival rates were (37.5 +/- 6.4)% and (15.0 +/- 1.8)%, respectively. The
      early apoptosis rate was (14.8 +/- 0.6)% and (30.8 +/- 1.5)%, significantly lower
      than that [(28.7 +/- 0.6)% and (46.6 +/- 2.8)%] after treatment in combination
      with TRAIL (P < 0.05). The expressions of TRAIL receptors and decoy receptors
      were increased when SNK-6 cells were treated with 100 ng/ml doxorubicin for 24
      hours. CONCLUSIONS: Doxorubicin can overcome to a certain extent the TRAIL
      resistance of SNK-6 cells and induce upregulation of TRAIL death receptors and
      decoy receptors on the surface of SNK-6 cells. However, a higher dose is needed.

PMID- 24332051
TI  - [Inhibitory effect of E2F-1-silencing lentivirus vector on chemoresistance of
      subcutaneous human gastric cancer in nude mice].
AB  - OBJECTIVE: To study the effects of E2F-1-silencing lentivirus vector on the
      growth and chemoresistance of subcutaneous human gastric cancer in nude mice.
      METHODS: Thirty-six nude mice were inoculated subcutaneously with chemoresistant
      SGC-7901/DDP cells to establish subcutaneous tumor models of gastric carcinoma.
      The mice were randomly divided into E2F-1/RNAi-LV group, LV-scrRNAi group and PBS
      group (n = 12). E2F-1/RNAi-LV, LV-scrRNAi or PBS (0.1 ml per time) was injected
      into the mice, respectively, every two days. The nude mice received an
      intraperitoneal injection of cisplatin (25 mg/kg) every two days. The tumor
      volume was measured and histopathological changes of the tumors were observed by
      HE staining. The expressions of E2F-1, c-Myc, survivin, MDR1 and MRP were
      detected by semi-quantitative reverse transcription polymerase chain reaction (RT
      PCR) and Western blot. Apoptosis in tumor xenografts was determined by in situ
      TUNEL labeling technique. RESULTS: The mean tumor growth rate of the E2F-1/RNAi
      LV group was significantly slower than that of the LV-scrRNAi and control groups
      (P < 0.05). The tumor volume of the E2F-1/RNAi-LV group was (745.13 +/-
      154.42)mm(3), significantly lower than that of the LV-scrRNAi and PBS groups (P <
      0.05). Compared with that in the LV-scrRNAi and PBS groups, the expressions of
      mRNA and protein of E2F-1, c-Myc, survivin, MDR1 and MRP were significantly
      decreased in the E2F-1/RNAi-LV group (P < 0.05). The apoptotic rate in the E2F
      1/RNAi-LV treatment group was (27.5 +/- 9.7)%, significantly higher than (7.0 +/-
      1.1)% in the LV-scrRNAi group and (7.3 +/- 1.2)% in the PBS group (P < 0.05).
      CONCLUSION: Intra-tumoral injection of E2F-1/RNAi-LV shows significantly
      inhibitory effect on the tumor growth and chemoresistance of subcutaneous human
      gastric cancer in nude mice.

PMID- 24332052
TI  - [Mechanisms of antimicrobial peptide LL-37 in macrophage-promoted ovarian cancer
      cell proliferation].
AB  - OBJECTIVE: The aim of this study was to investigate the role of macrophages in
      promotion of ovarian tumor cell proliferation mediated by over-expression of
      antimicrobial peptide LL-37. METHODS: To co-culture ovarian tumor cells SKOV3,
      3AO and HO-8910 with macrophages. The Transwell((r)) inserts system was used in
      the co-culture model. The effect of macrophages promoted ovarian tumor cell
      proliferation was assessed by BrdU-ELISA and cell number counting. Expressions of
      mRNA and protein of LL-37 in the macrophages and SKOV3 cells were determined by
      RT-PCR and Western blot analysis. To observe that LL-37 is responsible for
      macrophage-promoted ovarian tumor cells growth, LL-37 neutralizing antibody was
      added to abrogate the LL-37 activation. RESULTS: The cell number assay showed
      that after 4 days coincubation with macrophages in the proportion of 1:0.5, the
      number of SKOV3 cells increased from (6.0 +/- 0.5)*10(4) to (11.8 +/- 1.3)*10(4),
      showing a significant difference (P < 0.05). It also showed that the growth of
      the SKOV3 cells was dependent on the macrophage number (P < 0.05). The number
      variability of 3AO and HO-8910 cells was as the same as SKOV3 cells upon co
      culture with macrophages. As determined by BrdU-ELISA, the resulted proliferation
      of ovarian tumor cells was similar to the result of cell number counting. RT-PCR
      and Western blot results showed that the expression of LL-37 mRNA and protein in
      the macrophages was remarkably enhanced in a time dependent manner upon
      coincubation with SKOV3 cells, but did not work in SKOV3 cells. BrdU-ELISA assay
      exhibited that treatment of cells with LL-37 significantly stimulated HO-8910 and
      3AO cell proliferation. Addition of LL-37 neutralizing antibody markedly
      inhibited macrophage-promoted ovarian tumor cell (SKOV3, 3AO and HO-8910 cells)
      proliferation. The OD values of these three cells were decreased from 2.95 +/-
      0.11 to 1.45 +/- 0.04, from 3.39 +/- 0.36 to 1.32 +/- 0.09 and from 3.93 +/- 0.17
      to 1.68 +/- 0.23, respectively (P < 0.05). CONCLUSIONS: Over-expression and
      release of LL-37 from macrophages is responsible for proliferation of ovarian
      tumor cells in co-culture condition. The data presented indicate that LL-37 may
      be critical for macrophage-induced tumor progression.

PMID- 24332054
TI  - [Detection and clinical significance of platelet derived growth factor-BB and
      microvessel density in clear cell renal cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of platelet derived growth factor-BB
      (PDGF-BB) and microvessel density (MVD) marked with CD34 in clear cell renal cell
      carcinoma (CCRCC) and explore their relevance to clinicopathologic features and
      prognoses of patients. METHODS: Expressions of PDGF-BB and CD34 in the tissue
      samples of 100 clear cell renal cell carcinomas were detected by
      immunohistochemical (IHC) SP staining. The microvessel density (MVD) was counted
      using Weidner's method. For PDGF-BB assessment, the staining intensity and the
      proportion of positive tumor cells were analyzed. Staining was considered
      immunoreactive when brown granules were identified in the cytoplasm or nuclei of
      tumor cells. Staining intensity and the proportion of positively stained tumor
      cells in lesions was scored for further analysis. Statistical analysis was
      performed using the software SPSS 18.0. RESULTS: The MVD value marked by CD34 in
      the 100 cancer tissues was (105.49 +/- 37.95) profiles/HPF. The median value of
      MVD in the entire cohort was used as the cut-off point for low MVD group (42
      cases) and high MVD group (58 cases). The MVD of the low and high MVD groups was
      (75.12 +/- 22.41) profiles/ HPF and (135.86 +/- 22.91) profiles/HPF,
      respectively, with a statistically significant difference (P < 0.001). MVD was
      significantly correlated with the tumor T staging, histopathological grading and
      postoperative metastasis in CCRCC (P < 0.05, respectively). Among the 100 CCRCC
      cases, there were 38 cases with low PDGF-BB expression and 62 cases with high
      PDGF-BB expression, and the expression of PDGF-BB was significantly correlated
      with tumor diameter, T staging, histopathological grading and postoperative
      metastasis in the CCRCC (P < 0.05, respectively). Kaplan-Meier survival analysis
      showed that the cancer specific survival (CSS) in CCRCC patients with high
      expression of MVD and PDGF-BB was significantly better than that in the group
      with low MVD and low PDGF-BB expression (P < 0.001, respectively). Expression of
      PDGF-BB protein was positively associated with the MVD assessed by Spearman's
      correlation and factor analysis (r = 0.461, P < 0.001). CONCLUSION: Significantly
      increased MVD and PDGF-BB expression detected in CCRCC patients indicate a better
      tumor grading and staging, and a longer survival time.

PMID- 24332053
TI  - [Correlation analysis between abundance of K-ras mutation in plasma free DNA and
      its correlation with clinical outcome and prognosis in patients with metastatic
      colorectal cancer].
AB  - OBJECTIVE: To detect K-ras gene mutations in plasma free DNA by peptide nucleic
      acid clamp PCR assay (PNA-PCR) and nested primer PCR, and to analyze the
      correlation between K-ras mutations and prognosis in patients with metastatic
      colorectal cancer (mCRC). METHODS: Peripheral blood was collected and free DNA
      was extracted from plasma in 106 patients with mCRC. Nested primer PCR and PNA
      PCR were used to detect K-ras gene mutation in the plasma free DNA. The patients
      were divided into three groups by K-ras status: wild-type group (wild-type
      determined by both methods), low mutation group (mutation by PNA-PCR method, wild
      type by nested primer PCR method) and high mutation group (mutation by two
      methods). The correlation between K-ras mutations and prognosis was analyzed.
      RESULTS: The mutation rate of K-ras in tumor tissues of the 106 patients was
      40.6%. The Mutation rate of K-ras in plasma free DNA detected by PNA-PCR was
      31.1%, significantly higher than that of 15.1% detected by nested primer PCR (P =
      0.006). The consistent rate of the K-ras status in plasma free DNA detected by
      PNA-PCR and that in tumor tissue detected by traditional method was up to 83.0%.
      The median overall survival (OS) of patients of the wild type, low mutation and
      high mutation groups was 23.5 months, 17.3 months and 13.9 months, respectively
      (P = 0.002). The median progression-free survival (PFS) of the K-ras wild-type,
      low mutation and high mutation groups with first-line chemotherapy was 6.8
      months, 6.1 months and 3.2 months, respectively (P = 0.002), and the median OS of
      them were 23.0 months, 15.5 months and 13.9 months, respectively (P = 0.036). The
      overall response rate (ORR) was improved in the K-ras wide-type patients who
      received cetuximab combined with chemotherapy as first-line therapy (75.0% vs.
      23.4%, P = 0.058). Cetuximab combined with in second-line therapy chemotherapy
      led to a significant improvement in disease control rate (DCR) ( 100% vs. 35.7%,
      P < 0.001) as compared with those of chemotherapy alone. COX regression model
      showed that K-ras status detected by PNA-PCR, ECOG PS, number of surgery and
      initially metastatic site were independent factors for prognosis. CONCLUSIONS:
      PNA-PCR for the detection of K-ras mutation in plasma free DNA can be used to
      substitute the traditional method for detection of K-ras mutation in tumor
      tissues. The abundance of K-ras mutation in plasma free DNA is an independent
      prognostic factor for patients with metastatic colorectal cancer.

PMID- 24332055
TI  - [Clinicopathological and prognostic significance of ERalpha and ERbeta expression
      in lung carcinomas: a tissue microarray study].
AB  - OBJECTIVE: To detect the expression of ERalpha and ERbeta in lung carcinomas and
      investigate their clinicopathological and prognostic significance by using tissue
      microarray assay and immunohistochemical staining. METHODS: Six hundred and
      ninety-eight lung cancer specimens were used in this study, including 651 cases
      of non-small cell lung carcimomas (NSCLCs) and 47 cases of small cell lung
      cancers (SCLCs). There were 309 cases of adenocarcimoma and 342 cases of squamous
      cell carcinoma. The expression of ERalpha and ERbeta was analyzed by
      immunohistochemistry on paraffin-embedded sections. RESULTS: In the normal lung
      tissues, expression of ERalpha and ERbeta was 0% (0/35) and 25.0% (9/36),
      respectively. In the tumor tissues, ERalpha was expressed in 209 of 295 AC cases
      (70.8%), 169 of 330 SCC cases (51.2%) and 9 of 47 SCLC cases (19.1%) (P < 0.001).
      ERbeta was expressed in 200 of 297 AC cases (67.3%), 140 of 322 SCC cases (43.5%)
      and 31 of 47 SCLC cases (66.0%) (P < 0.001). In NSCLC, the expression of ERalpha
      and ERbeta was significantly associated with smoking, stage and lymph node
      metastasis, also with sex refer to ERbeta (P < 0.05), but not significantly with
      age, tumor size and degree of differentiation (P > 0.05). Follow-up was completed
      in 398 NSCLC cases, and no significant correlation was found between the
      prognosis and expression of ERalpha and ERbeta. CONCLUSIONS: The expression of
      ERalpha and ERbeta has significant difference in lung adenocarcinoma, squamous
      cell carcinoma and small cell lung cancer. In NSCLC, expression of ERalpha and
      ERbeta is associated with smoking, stage, and lymph node metastasis. The
      expression of ERbeta is higher in female than in male NSCLC patients.

PMID- 24332056
TI  - [Relationship between HPV-DNA status and p16 protein expression in oropharyngeal
      squamous cell carcinoma and their clinical significance].
AB  - OBJECTIVE: To investigate the relationship between HPV-DNA status and p16 protein
      expression in oropharyngeal squamous cell carcinoma (OSCC) and their clinical
      significance. METHODS: Sixty-six patients with oropharyngeal squamous cell
      carcinomas treated in the Cancer Hospital of Chinese Academy of Medical Sciences
      from Jan. 1999 to Dec. 2009 were included in this study. Their formalin-fixed and
      paraffin-embedded tumor tissue blocks met the eligibility criteria and were used
      in this study. A "sandwich" technique was used to prepare paraffin sections for
      HPV-DNA analysis. HPV-DNA was detected using the SPF10 LiPA25 version 1 assay.
      The expression of p16 protein was detected by immunohistochemistry. The survival
      rates of patients with different HPV-DNA and p16 protein status were analyzed.
      RESULTS: HPV-DNA was detected in 11 (16.7%) of all specimens. Expression of p16
      protein was detected in 9 of the 11 patients with HPV-positive tumors, and in 12
      patients of 55 HPV-negative tumors. The expression of p16 protein was highly
      correlated with the presence of HPV-DNA (P < 0.001). The tumors were classified
      into three groups based on the p16 protein expression and HPV-DNA status: group A
      (9 patients): HPV(+) and p16 protein(+); group B (14 patients): HPV-DNA(+)/p16
      protein(-) or HPV-DNA(-)/p16 protein(+); and group C (43 patients): HPV-DNA(
      )/p16 protein(-). The 3-year OS rates of these 3 groups were 100%, 77.8% and
      42.0% (P = 0.001), and their DSS rates were 100%, 77.8% and 46.4%, respectively(P
      = 0.004). CONCLUSIONS: In oropharyngeal squamous cell carcinomas, p16 protein
      expression is highly correlated with the presence of HPV-DNA, and might be a
      surrogate marker for HPV-positive OSCC. Combination of p16 protein and HPV-DNA
      status detection may help to more accurately stratify oropharyngeal carcinomas
      and predict their prognosis.

PMID- 24332057
TI  - [Clinicopathological and survival features of primary hepatic lymphoma: an
      analysis of 35 cases].
AB  - OBJECTIVE: To evaluate the clinicopathological features and prognosis of primary
      hepatic lymphoma (PHL). METHODS: Thirty-five patients with PHL who underwent
      surgical resection and were confirmed by pathology in our hospital from 1982 to
      2012 were re-evaluated for clinicopathological data, including their symptoms,
      radiological features, recurrence interval, histopathological properties and
      prognosis. RESULTS: Of the 35 patients, 25 were men (71.4%) and 10 were women
      (28.6%), with an average age of 52.6 years old (range, 17-79 years). Presented
      symptoms were epigastric phymatosis, abdominal pain and low-grade fever. In the
      present study, 21 (60.0%) patients were positive for HBsAg, 1(2.9%) patient was
      positive for anti-HCV, 3 patients were positive for AFP, 12 patients and 2
      patients were complicated by cirrhosis and hepatocellular carcinoma,
      respectively. Pathologically, 35 PHL were classified into 19 DLBCL (54.3%), 13 T
      cell-lymphoma (37.1%), and 3 MALT lymphoma (8.6%). Patients with DCBCL showed
      better postoperative survival than patients with T cell-lymphoma (31.7 +/- 3.2)
      months vs. (22.9 +/- 2.2) months (P < 0.05). CONCLUSIONS: Hepatitis B virus (HBV)
      infection may contribute to the pathogenesis of Chinese patients with PHL.
      Surgical resection followed by comprehensive therapy is the first-line option for
      PHL. The prognosis of patients with PHL is associated with PHL subtypes.

PMID- 24332058
TI  - [Analysis of the prognosis of 111 patients with gastric cancer or adenocarcinoma
      of the esophagogastric junction combined with pleural or abdominal effusion].
AB  - OBJECTIVE: To explore the prognostic factors in patients with gastric cancer (GC)
      or adenocarcinoma of the esophagogastric junction (AEG) combined with malignant
      pleural and/or abdominal effusion. METHODS: Clinicopathological data of 111 GC or
      AEG patients with malignant pleural and/or abdominal effusion treated in our
      hospital from January 2001 to December 2010 were retrospectively analyzed.
      RESULTS: The median survival time for the whole group of 111 patients was 6
      months. Effusion disappeared in 12 patients, was reduced in 36 cases, with no
      changes in 15 cases, and increased in 48 patients. The effusion control rate was
      56.8%. Effusion was better controlled in female patients, with simple abdominal
      ascites, Karnovsky performance scores >= 80, with no liver metastases, effusion
      at initial diagnosis, and effective response to systemic chemotherapy.Univariate
      analysis showed that patients of female sex, Karnovsky performance scores >= 80,
      effusion present at initial diagnosis, simple abdominal ascites, minimal volume
      of effusion, absence of liver metastasis, control of effusion, initial treatment
      with effusions and effective response to systemic chemotherapy, normal
      hemoglobin, albumin, direct and indirect bilirubin levels showed better prognosis
      (all P < 0.05). Multivariate analysis showed that liver metastases, control of
      effusions were independent prognostic factors in patients with gastric cancer and
      adenocarcinoma of the esophagogastric junction (all P < 0.05). CONCLUSIONS:
      Female patients, simple abdominal ascites, KPS scores >= 80, ascites at initial
      diagnosis, no liver metastases and effective systemic chemotherapy seem to have a
      better control of the malignant effusion. Patients with no liver metastases and
      effective control of effusion have a longer survival time.

PMID- 24332059
TI  - [Value of narrow band imaging endoscopy in the detection of unknown primary site
      with cervical lymph node metastasis of squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the value of narrow band imaging (NBI) endoscopy in the
      detection of unknown primary tumor site with cervical lymph node metastases of
      squamous cell carcinoma. METHODS: Fifty-three patients with cervical lymph node
      metastases of squamous cell carcinoma treated in our department between June 2009
      and December 2011 were enrolled in this study. Their primary tumor site was not
      detected by routine computed tomography, magnetic resonance imaging and
      laryngoscopy. The nasopharyngolarynx was examined by NBI endoscopy to explore the
      primary tumor site. RESULTS: A total of 53 cases with cervical lymph node
      metastasis of squamous cell carcinoma from an unknown primary were examined under
      NBI endoscopy. The primary tumor site was confirmed by NBI examination in 47.2%
      (25/53) of patients, significantly better than routine radiology and endoscopy
      (0, P < 0.001). These primary tumors were small and superficial, with
      characteristic mucosal vascular morphologies. The superficial nasopharyngeal
      carcinomas under NBI examination showed the superficial thin branch-like or
      torturous line microvessels. The notable characteristics of the squamous cell
      carcinoma of oropharynx, hypopharynx and larynx was the well demarcated brownish
      area and scattered brown dots. CONCLUSION: The NBI endoscopy can provide better
      visualization of the morphology of superficial mucosal vasculature and improve
      the ability to detect possible primary cancer in patients with primary unknown
      cervical lymph node metastasis.

PMID- 24332060
TI  - [Diagnostic value of automated breast volume scanner in high-risk and small
      breast lesions].
AB  - OBJECTIVE: To assess the accuracy of detection by automated breast volume scanner
      (ABVS) in diagnosis of high-risk and small breast lesions. METHODS: One hundred
      and twelve patients with solid high-risk and small breast lesions were identified
      by ABVS. The patients were divided into benign lesion group and cancer group
      after pathological examination. The clinicopathological findings and
      ultrasonographic features of the lesions were compared. RESULTS: Among the 112
      lesions there were 49 benign and 63 malignant lesions. The mean size on ABVS and
      pathology were (1.59 +/- 0.52) cm and (1.52 +/- 0.58) cm. There was no
      significant difference in tumor sizes determined by ABVS and pathology (P =
      0.194). The mean age of patients with benign lesions was (38.5 +/- 7.4) years and
      that of malignant lesions was (52.4 +/- 13.6) years, showing a significant
      difference between the two groups (P < 0.001) . The mass shape, orientation,
      margin, lesion boundary, echo pattern, calcification, BI-RADS category and
      retraction phenomenon were significantly different of the malignant and benign
      masses (P < 0.05). But there was no significant difference in the location of
      lesions and posterior acoustic features (P > 0.05) . Retraction phenomenon was
      significantly associated with pathological type and histologic grade of the
      breast cancer (P < 0.01). The specificity, sensitivity and accuracy of retraction
      phenomenon were 100% (46/46), 73.0% (46/63), and 84.8% (95/112), respectively.
      CONCLUSIONS: ABVS provides advantages of better size prediction of high-risk and
      small breast lesions. Furthermore, the retraction phenomenon in coronal plane
      shows high specificity and sensitivity in detecting breast cancer.

PMID- 24332062
TI  - [Analysis of mortality and years of life lost of malignant tumors among
      inhabitants in rural area of Feicheng city from 2000 to 2010].
AB  - OBJECTIVE: To analyze the mortality trends and disease burden of malignant tumors
      in rural area of Feicheng city from 2000 to 2010, and to provide basic
      information for the prevention and treatment of malignant tumors in this area.
      METHODS: The data of cancer mortality from 2000 to 2010 from Feicheng Cancer
      Registry database were checked. Mortality rate, standardized mortality rate,
      potential years of life Iost (PYLL), standardized potential years of life lost
      (SPYLL), average years of life lost (AYLL) and other indexes were calculated and
      analyzed. The trend of the standardized rates transformed by the natural
      logarithm over time was assessed by Prais-Winsten regression method in which the
      errors was assumed to follow a first-order autoregressive process. STATA 12.0 was
      used to analyze the data. RESULTS: In average, the crude mortality rate was
      199.67 per 100 000 (264.69 per 100 000 in males and 137.24 per 100 000 in
      females), and the standardized mortality rate was 157.00 per 100 000 (200.49 per
      100 000 in males and 101.31 per 100 000 in females). There were no significant
      changes in the trends of all standardized rates. For males, the mortality rates
      of lung and colorectal cancers increased significantly, and for females, the
      rates of lung and breast cancers had increased trend while the rate of esophageal
      cancer showed a downward trend. There were no statistically significant changes
      in other main malignant tumors. During 2000 to 2010, the PYLL of malignant tumors
      in Feicheng was 183 685.0 person-years, and PYLL rate was 23.3 per 1000. The
      SPYLL was 153 091.0 person-years, SPYLL rate was 19.4 per 1000, and AYLL was 14.8
      years. CONCLUSIONS: There are no obvious changes in the trends of standardized
      mortality rates in rural area of Feicheng over the past 11 years. For males, the
      mortality of lung cancer and colorectal cancer is increasing, and for females,
      the rates of lung and breast cancers have an increasing trend while the rate of
      esophageal cancer shows a decreasing trend. The prevention and control of
      digestive malignant tumors, lung cancer and breast cancer are getting seriously
      important and should be the focal point in this issue.

PMID- 24332061
TI  - [Value of postoperative adjuvant chemotherapy in locally advanced rectal cancer
      patients with ypT1-4N0 after neo-adjuvant chemoradiotherapy].
AB  - OBJECTIVE: The purpose of this study was to investigate the value of
      postoperative chemotherapy for locally advanced rectal cancer patients who
      reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy. METHODS: We
      performed a retrospective study of 104 patients treated with preoperative
      chemoradiotherapy followed by radical resection, who achieved pathological ypT1
      4N0, between Mar 2003 and Dec 2010. There were 73 patients who received
      postoperative adjuvant chemotherapy, and the other 31 patients did not. The
      distribution of final pathologic stages for these patients was ypT1-2N0 in 39
      cases and ypT3-4N0 in 65 cases. RESULTS: The median follow-up was 41 months. The
      3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the
      whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS
      in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were
      95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant
      differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups.
      The 3-year local recurrence and distant metastasis rates in the adjuvant
      chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant
      chemotherapy group, the 3-year local recurrence rate and distant metastasis rate
      were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found
      in distant metastasis rates (P = 0.030) between the two groups, but not in local
      recurrence rates (P = 0.676).Further subgroup analysis indicated that for the
      ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296)
      and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups,
      while negative results displayed in 3-year local recurrence rates (P = 0.676) and
      distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0,
      significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P
      = 0.025), and further analysis revealed that the 3-year distant metastasis rate
      was significantly higher in the non-adjuvant chemotherapy group than in the
      adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in
      the 3-year local recurrence (P = 0.548). CONCLUSIONS: Adjuvant chemotherapy may
      not improve survival for ypT1-2N0 patients. However, it may be clinically
      meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further
      randomized controlled clinical trials are needed to confirm our results.

PMID- 24332064
TI  - A proteomic approach of SigX function in Pseudomonas aeruginosa outer membrane
      composition.
AB  - SigX is one of the 19 extracytoplasmic function sigma factors that have been
      predicted in the human opportunistic pathogen Pseudomonas aeruginosa genome. SigX
      is involved in the transcription of oprF, encoding the major outer membrane
      protein OprF, a pleiotropic porin that contributes to the maintaining of the wall
      structure, and is essential to P. aeruginosa virulence. This study aimed to get
      further insights into the functions of SigX. We performed here an outer membrane
      subproteome of a sigX mutant. Proteomic investigations revealed lower production
      of 8 porins among which 4 gated channels involved in iron or hem uptake, OprF,
      and the three substrate-specific proteins OprD, OprQ and OprE. On the other side,
      the glucose-specific porin OprB and the lipid A 3-O-deacylase that is involved in
      LPS modification were up-regulated. Our results indicate that SigX may be
      involved in the control and/or regulation of the outer membrane composition.
      BIOLOGICAL SIGNIFICANCE: A proteomic approach was used herein to get further
      insights into SigX functions in P. aeruginosa. The data presented here suggest
      that SigX is involved in the outer membrane protein composition, and could be
      linked to a regulatory network involved in OM homeostasis.

PMID- 24332063
TI  - Plasma microparticle tissue factor activity in patients with antiphospholipid
      antibodies with and without clinical complications.
AB  - Antiphospholipid syndrome (APS) is defined by the association of autoantibodies
      to certain phospholipid-binding proteins with arterial or venous thrombosis ('AT'
      or 'VT', respectively), and/or pregnancy-related morbidity (PM). Antiphospholipid
      antibodies (aPLA) promote activation of several cell types including monocytes,
      resulting in procoagulant tissue factor (TF) expression that may contribute to
      the vascular complications. Since TF synthesis by monocytes is frequently
      accompanied by release of TF-bearing microparticles, we hypothesized that plasma
      microparticle TF activity (MP-TF) may be elevated in APS patients and contribute
      to thrombosis and/or PM. Platelet-poor plasma specimens were obtained from 30
      patients with definite APS and 72 patients with asymptomatic aPLA from the
      Antiphospholipid Syndrome Collaborative Registry (APSCORE). MP-TF was measured by
      an in-house factor Xa generation assay. The two groups were well matched for
      gender, age, ethnicity, proportions with underlying SLE, and aPLA profiles. MP-TF
      (median and (IQR)) in asymptomatic aPLA subjects was 0.09 pg/mL (0.05-0.14)
      compared to 0.13 pg/mL (0.10-0.17) in APS (p < 0.001). No differences in MP-TF
      levels were observed between APS subjects with PM, thrombosis, or PM+thrombosis.
      Similarly, among subjects with either APS or asymptomatic aPLA, MP-TF did not
      differ in the presence or absence of underlying SLE. Prospective studies will be
      required to determine if plasma MP-TF activity is causally related to thrombotic
      or gestational complications in APS.

PMID- 24332065
TI  - Up-regulation of type I collagen during tumorigenesis of colorectal cancer
      revealed by quantitative proteomic analysis.
AB  - Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. The
      discovery of non-invasive biomarker candidates for diagnosis and prognosis is
      important for the management of CRC. In this study, we performed proteomic
      profiling of serum from patients with different stages of CRC using a 2D-LC-MS/MS
      based approach combined with the APEX quantitative method. 917 proteins were
      identified and 93 were differentially expressed in normal and three patient
      groups (stages I, II and III). These proteins were predominantly involved in cell
      adhesion, immune response, coagulation process and metabolism. Importantly, we
      found collagen I dynamically changed from stages I to IV, with maximum expression
      in stage II, as detected in serum by MS analysis. Expression of collagen I was
      also validated in tumor tissues from the same group of CRC patients by real-time
      PCR and western blotting. Furthermore, we demonstrate that serum levels of
      collagen I degradation telopeptide (CTx) are correlated with staging and poor
      disease-free survival of CRC patients by ELISA analysis. These results suggest
      (1) serum proteomics may reflect biological changes in colorectal tumor tissues
      and (2) altered collagen I expression may be an early event in CRC tumorigenesis
      and CTx may provide additional information for prognosis of CRC. BIOLOGICAL
      SIGNIFICANCE: In this work, we performed a systematic characterization of serum
      proteomic alterations in colorectal cancer (CRC) with different stages using a LC
      MS based approach combined with the APEX quantitative method, attempting to gain
      overview of relevant proteins in tumorigenesis and discover non-invasive CRC
      derived markers. We found a significant up-regulation of collagen I based on the
      proteomics data, and confirmed its expression in tissue and serum of the same
      group of patients. In addition, we also demonstrated that serum levels of
      collagen I degradation telopeptide (CTx) are correlated with the staging and poor
      survival rate of CRC. Those findings imply that alternation of collagen I might
      be an early event during tumorigenesis of CRC, and might contribute to the
      metastasis of CRC under the degradation regulated by some specific proteases.
      This work provides evidence for the clinical application of serum proteomics, and
      would aid the understanding of the role of the ECM in the clinical progression of
      CRC.

PMID- 24332067
TI  - Bernard Lown's legacy: from avoidable care to right care.

PMID- 24332066
TI  - Activation of protein kinase C delta by psideltaRACK peptide promotes embryonic
      stem cell proliferation through ERK 1/2.
AB  - The protein kinase C (PKC) family of serine/threonine kinases participate in
      embryonic stem cell (ESC) proliferation/self-renewal. A few stimuli that induce
      ESC proliferation activate several PKC isoenzymes including deltaPKC, however,
      the role of this isoenzyme under basal conditions that maintain undifferentiated
      ESCs remains to be determined. Herewith, we aimed to characterize signaling
      events that occur in undifferentiated ESCs upon deltaPKC activation. Using
      phosphoproteomics and a deltaPKC specific activator peptide, psideltaRACK, it was
      seen that the majority of proteins whose phosphorylation increased upon deltaPKC
      activation participate in cell proliferation. Network analysis of these proteins
      directly connected deltaPKC to Raf1 and 14-3-3. Experimental validation studies
      showed that activation of deltaPKC increased its binding to 14-3-3, transiently
      activated ERK1/2 and increased ESC proliferation. Independently inhibiting MEK or
      PI3 kinase both led to a decrease in proliferation of approximately 50%, but
      deltaPKC activation only recovered the effect of PI3 kinase inhibition suggesting
      that ERK1/2 activation via deltaPKC is probably a parallel pathway to PI3 kinase
      and that both pathways are necessary for undifferentiated ESC proliferation.
      BIOLOGICAL SIGNIFICANCE: The use of embryonic stem cells and induced pluripotent
      stem cells for regenerative therapies is still a challenge. Understanding the
      underlying mechanisms that keep these cells proliferating with the ability to
      differentiate in more than 200 cell types (self-renewal) will aid in the future
      use of these cells therapeutically. Using a targeted phosphoproteomics study,
      insights into signaling pathways involved in ESC proliferation can be obtained.
      Modulating these pathways will aid the obtention of a larger number of self
      renewing stem cells and induced pluripotent stem cells that can be used
      therapeutically.

PMID- 24332068
TI  - HIV in Iran.

PMID- 24332069
TI  - China tackles the health effects of air pollution.

PMID- 24332071
TI  - Deenan Pillay: virologist in HIV's heartlands.

PMID- 24332072
TI  - Erosion of universal health coverage in Spain.

PMID- 24332073
TI  - Economic crisis and mental health in Spain.

PMID- 24332074
TI  - Economics should incorporate ethical considerations.

PMID- 24332075
TI  - Polio eradication: where are we now?

PMID- 24332076
TI  - Child marriage in Yemen.

PMID- 24332077
TI  - Political Lancet.

PMID- 24332078
TI  - Political Lancet.

PMID- 24332079
TI  - Bilateral visual loss in a patient with endocarditis.

PMID- 24332080
TI  - EUS-guided hepatogastrostomy with double stenting.

PMID- 24332081
TI  - The current practice standard for colonoscopy in Australia.
AB  - BACKGROUND: Despite having one of the highest rates per capita for colonoscopy
      worldwide, colorectal cancer remains the second most commonly diagnosed
      malignancy in Australia. OBJECTIVE: Our aim was to document
      colonoscopy/polypectomy practice nationwide and assess whether significant
      differences exist. DESIGN: Observational study. SETTING: Online survey conducted
      nationally in 2012. PARTICIPANTS: Medical practitioners registered with the
      Gastroenterological Society of Australia practicing colonoscopy. MAIN OUTCOME
      MEASUREMENTS: Rates of polypectomy techniques for varying polyp sizes,
      postpolypectomy bleeding prophylaxis techniques, and adenoma detection practices.
      To assess whether variations exist according to practice location, specialty, and
      experience and comparison of practice with a previous American cohort. RESULTS:
      Of the 846 members contacted, 244 (28.8%) responded. The cohort consisted
      primarily of consultant gastroenterologists (182/244, 74.6%). The cold-snare
      technique was preferred (165/244, 67.6%) for polyps 3 mm in size; however, this
      decreased rapidly with increasing polyp size (5 mm [120/244, 49.2%] and 7-9 mm
      [18/244, 7.4%]). EMR was the preferred method of resection for polyps 7 to 9 mm
      in size (148/244, 60.7%). The withdrawal technique predominantly consisted of
      double-passing high-risk areas and rectal retroflexion (134/244, 54.9%).
      Significant differences across specialty, location, and experience included
      polypectomy method for diminutive polyps, the use of EMR, and retroflexion.
      LIMITATIONS: Survey-based study and response rate. CONCLUSION: Although
      variations in colonoscopy and polypectomy practice exist, the majority of our
      cohort performs cold-snare polypectomy for diminutive polyps and pass high-risk,
      poorly visualized areas twice on withdrawal. This is a significant shift in
      practice from that of the U.S. cohort studied 10 years earlier.

PMID- 24332082
TI  - Endoscopic suturing closure of large mucosal defects after endoscopic submucosal
      dissection is technically feasible, fast, and eliminates the need for
      hospitalization (with videos).
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is less invasive than surgical
      resection, but the large mucosal defects after ESD may lead to adverse events
      necessitating hospitalizations. OBJECTIVE: To evaluate the use of an endoscopic
      suturing device for closure of large mucosal defects after ESD. DESIGN AND
      SETTING: Retrospective, single-center study. PATIENTS: Twelve consecutive
      patients underwent ESD. INTERVENTIONS: All lesions were removed by using a
      previously described ESD technique. The large mucosal defects post-ESD were
      completely closed with the endoscopic suturing device, and all patients were
      discharged home with subsequent clinical and endoscopic follow-up. MAIN OUTCOME
      MEASUREMENTS: Bleeding and perforation rates after ESD with mucosal defect
      closure. RESULTS: ESD followed by endoscopic suturing of the mucosal defects was
      performed in 12 patients (mean age, 64.7 +/- 11.2 years, 4 lesions in the
      stomach, 8 lesions in the colon; mean lesion size, 42.5 +/- 14.8 mm) over a
      period of 8 months. All lesions (100%) were removed en bloc. Closure of post-ESD
      defects with an endoscopic suturing device was technically feasible and fast
      (mean closure time, 10.0 +/- 5.8 minutes per patient). Only 1 stitch (continuous
      suturing line) was required for complete closure in 8 patients. In the other 4
      patients, the mucosal defect was closed with 2 to 4 separate stitches (mean
      number of sutures per patient, 1.6 +/- 1.0). There were no immediate or delayed
      adverse events in any of the study patients. LIMITATIONS: Retrospective study.
      CONCLUSIONS: Closure of large post-ESD defects with the Overstitch endoscopic
      suturing device is technically feasible and fast and can significantly decrease
      treatment cost by eliminating the need for hospitalization.

PMID- 24332084
TI  - The Brugada syndrome revisited.
AB  - The Brugada syndrome is a rare but well-defined cause of sudden cardiac death.
      The key underlying abnormality is a decrease in net depolarising current due to a
      genetic defect, though recent evidence also implicates structural abnormalities
      in some patients. Diagnosis requires a Brugada-type ECG as well as typical
      clinical features: such clinical considerations are currently key in guiding risk
      stratification and hence management. Whilst pharmacological therapies are under
      investigation, the only intervention with a robust evidence base remains
      insertion of an implantable cardioverter defibrillator. Further research will be
      required to allow more effective risk stratification and hence more rational
      therapy. 

PMID- 24332083
TI  - The Structural Basis of Functional Improvement in Response to Human Umbilical
      Cord Blood Stem Cell Transplantation in Hearts With Postinfarct LV Remodeling.
AB  - Cellular therapy for myocardial repair has been one of the most intensely
      investigated interventional strategies for acute myocardial infarction. Although
      the therapeutic potential of stem cells has been demonstrated in various studies,
      the underlying mechanisms for such improvements are poorly understood. In the
      present study, we investigated the long-term effects of stem cell therapy on both
      myocardial fiber organization and regional contractile function using a rat model
      of postinfarct remodeling. Human nonhematopoietic umbilical cord blood stem cells
      (nh-UCBSCs) were administered via tail vein to rats 2 days after infarct surgery.
      Animals were maintained without immunosuppressive therapy. In vivo and ex vivo MR
      imaging was performed on infarct hearts 10 months after cell transplantation.
      Compared to the age-matched rats exposed to the identical surgery, both global
      and regional cardiac functions of the nh-UCBSC-treated hearts, such as ejection
      fraction, ventricular strain, and torsion, were significantly improved. More
      importantly, the treated hearts exhibited preserved fiber orientation and water
      diffusivities that were similar to those in sham-operated control hearts. These
      data provide the first evidence that nh-UCBSC treatment may prevent/delay
      untoward structural remodeling in postinfarct hearts, which supports the improved
      LV function observed in vivo in the absence of immunosuppression, suggesting a
      beneficial paracrine effect occurred with the cellular therapy. 

PMID- 24332085
TI  - What's for lunch? An analysis of lunch menus in 83 urban and rural Oklahoma child
      care centers providing all-day care to preschool children.
AB  - BACKGROUND: More than half of 3- to 6-year-old children attend child-care
      centers. Dietary intakes of children attending child-care centers tend to fall
      short of Dietary Reference Intakes (DRIs). OBJECTIVE: Our aim was to examine
      macro-/micronutrient content of child-care center menus, compare menus to one
      third of DRIs, and determine menu differences by population density. METHODS: A
      stratified, random, geographically proportionate sample of Oklahoma child-care
      centers was obtained. Child-care centers providing all-day care for 2- to 5-year
      old children were contacted to complete a telephone questionnaire and asked to
      send in that month's menus for the 3- to 4-year-old children. Overall means and
      standard deviations of the nutrient content of 5 days of lunch menus were
      calculated. Comparisons were made to both the 1- to 3-year-old and 4- to 8-year
      old DRIs. One-sample t tests compared mean nutrient content of lunches to one
      third of the DRIs for the overall sample and urban/rural classification.
      Independent t tests compared nutrient content of urban and rural lunches.
      PARTICIPANTS/SETTING: One hundred sixty-seven child-care centers were contacted;
      83 completed the study (50% response). RESULTS: Menus provided statistically
      significantly insufficient carbohydrate, dietary fiber, iron, vitamin D, and
      vitamin E. Calcium was higher than the 1- to 3-year-old DRI, but lower than the 4
      to 8-year-old DRI. Folate was higher than the 1- to 3-year-old DRI, but not
      different from the 4- to 8-year-old DRI. Sodium was higher than the DRI for both
      age groups. Thirty-four child-care centers (41%) were classified as urban and 49
      (59%) as rural. Urban menus provided less than the 4- to 8-year-old DRI for
      folate, but rural child-care center menus did not. CONCLUSIONS: Oklahoma child
      care center menus appear to provide adequate protein, magnesium, zinc, vitamin A,
      and vitamin C, but may be deficient in key nutrients required for good health and
      proper development in preschool-aged children. These issues can be addressed by
      including food and nutrition practitioners in the process to ensure child-care
      center menus are a useful resource and nutritionally appropriate for preschool
      children.

PMID- 24332086
TI  - Scratch test of thermoplastic denture base resins for non-metal clasp dentures.
AB  - PURPOSE: Several thermoplastic denture base resins have been introduced for the
      fabrication of non-metal clasp dentures. Although the surface of these materials
      is easily damaged, the surface roughness and characteristics of scratches created
      have not been evaluated. The purpose of this study was to evaluate the surface
      roughness of thermoplastic resins using a scratch test for the development of
      future materials. METHODS: Four thermoplastic (polyamide: Valplast((r)); VLP and
      Lucitone FRS((r)); FRS, polyethylene terephthalate: EstheShot((r)); ES, and
      polyester: EstheShot Bright((r)); ESB) and two conventional acrylic (Heat
      polymerizing: Urban((r)); HC, and Pour type auto-polymerizing: Pro-Cast DSP((r));
      PR) denture base resins were examined. Eight specimens, approximately
      10mm*10mm*30mm in size, of each material were fabricated. Scratch test was
      performed by a scratch tester with a diamond indenter of 10-MUm radius and cone
      angle 90 degrees , applying a constant load of 500mN, and 2-mm-long scratches
      were made. The scratch marks were studied under 3D laser measuring microscope and
      cross-section profiles at approximately 0.5mm, 1.0mm, and 1.5mm from the starting
      point were extracted and measured with analysis software. Data from 24 cross
      section profiles in each denture base material were analyzed. RESULTS: The
      maximum depths of ES, ESB and FRS were greater than VLP, PR and HC, and the
      scratch widths of ES, ESB, FRS and VPL were greater than PR and HC. CONCLUSIONS:
      The results showed that the surface of thermoplastic denture base resins was
      easily damaged compared to polymethyl methacrylate.

PMID- 24332087
TI  - Inflammatory tracheal pseudomembrane.

PMID- 24332088
TI  - Modulating the interaction between CDK2 and cyclin A with a quinoline-based
      inhibitor.
AB  - A new class of quinoline-based kinase inhibitors has been discovered that both
      disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act
      as ATP competitive inhibitors. The key strategy for discovering this class of
      protein-protein disrupter compounds was to screen the monomer CDK2 in an affinity
      selection/mass spectrometry-based technique and to perform secondary assays that
      identified compounds that bound only to the inactive CDK2 monomer and not the
      active CDK2/cyclin A heterodimer. Through a series of chemical modifications the
      affinity (Kd) of the original hit improved from 1 to 0.005MUM. 

PMID- 24332090
TI  - Synthesis and biological evaluation of the pirfenidone derivatives as
      antifibrotic agents.
AB  - A total of 24 pirfenidone derivatives were designed, synthesized and evaluated
      for their inhibitory activity against the human lung fibroblast cell line MRC-5.
      These compounds showed the remarkable proliferation inhibition against MRC-5
      compared to pirfenidone as the positive control. The possible mechanism of this
      kind of derivatives as antifibrotic agents was explored. The molecular docking
      and p38 binding affinity assays demonstrated that the antifibrotic potential of
      the pirfenidone derivatives was possibly through the inhibition of p38 MAPK
      signaling pathway. The data from this study suggested that p38 might be a
      potential therapeutic target for the new generation antifibrotics. All the
      pirfenidone derivatives are reported here for the first time. 

PMID- 24332089
TI  - Imidazole-derived agonists for the neurotensin 1 receptor.
AB  - A scaffold-hop program seeking full agonists of the neurotensin-1 (NTR1) receptor
      identified the probe molecule ML301 (1) and associated analogs, including its
      naphthyl analog (14) which exhibited similar properties. Compound 1 showed full
      agonist behavior (79-93%) with an EC50 of 2.0-4.1MUM against NTR1. Compound 1
      also showed good activity in a Ca mobilization FLIPR assay (93% efficacy at
      298nM), consistent with it functioning via the Gq coupled pathway, and good
      selectivity relative to NTR2 and GPR35. In further profiling, 1 showed low
      potential for promiscuity and good overall pharmacological data. This report
      describes the discovery, synthesis, and SAR of 1 and associated analogs. Initial
      in vitro pharmacologic characterization is also presented. 

PMID- 24332091
TI  - Oxidative cleavage of DNA by pentamethine carbocyanine dyes irradiated with long
      wavelength visible light.
AB  - Here we report the synthesis of seven symmetrical carbocyanine dyes in which two
      nitrogen-substituted benz[e]indolium rings are joined by a pentamethine bridge
      that is meso-substituted with chlorine or bromine versus hydrogen. The heteroatom
      of benz[e]indolium is modified with a phenylpropyl, methyl, or cationic
      quaternary ammonium group. In reactions containing micro molar concentrations of
      halogenated dye, irradiation at 575, 588, 623, or 700nm produces good
      photocleavage of plasmid DNA. UV-visible spectra show that the carbocyanines are
      in their H-aggregated and monomeric forms. Scavenger experiments point to the
      involvement of singlet oxygen and hydroxyl radicals in DNA photocleavage. 

PMID- 24332092
TI  - Synthesis and biological properties of thiazole-analogues of pyochelin, a
      siderophore of Pseudomonas aeruginosa.
AB  - Pyochelin is a siderophore common to all strains of Pseudomonas aeruginosa
      utilized by this Gram-negative bacterium to acquire iron(III). FptA is the outer
      membrane transporter responsible of ferric-pyochelin uptake in P. aeruginosa. We
      describe in this Letter the synthesis and the biological properties ((55)Fe
      uptake, binding to FptA) of several thiazole analogues of pyochelin. Among them
      we report in this Letter the two first pyochelin analogues able to bind FptA
      without promoting any iron uptake in P. aeruginosa. 

PMID- 24332093
TI  - (E)-Alkenes as replacements of amide bonds: development of novel and potent
      acyclic CGRP receptor antagonists.
AB  - A new class of CGRP receptor antagonists was identified by replacing the central
      amide of a previously identified anilide lead structure with ethylene, ethane, or
      ethyne linkers. (E)-Alkenes as well as alkynes were found to preserve the proper
      bioactive conformation of the amides, necessary for efficient receptor binding.
      Further exploration resulted in several potent compounds against CGRP-R with low
      susceptibility to P-gp mediated efflux. 

PMID- 24332094
TI  - Development of the Pregnancy and Childbirth Questionnaire (PCQ): evaluating
      quality of care as perceived by women who recently gave birth.
AB  - OBJECTIVE: To develop an instrument to the assess quality of care during
      pregnancy and delivery as perceived by women who recently gave birth. STUDY
      DESIGN: Prospective design from focus group interviews to validation of the
      questionnaire. The focus groups consisted of seven care providers, ten pregnant
      women and six women who recently gave birth. With the results of the focus group
      interviews, a draft questionnaire of 52 items was composed and its psychometric
      properties were tested in a first cohort of 300 women who recently gave birth
      (sample I) by means of exploratory factor analysis (EFA) and reliability
      analysis. The final version was further explored by confirmatory factor analyses
      (CFA) in another sample of 289 women (sample II) with similar characteristics as
      sample I. RESULTS: EFA in sample I suggested an 18-item scale with two components
      concerning the quality of care during pregnancy: 'personal treatment' (11 items,
      Cronbach's alpha (alpha)=0.87) and 'educational information' (7 items,
      alpha=0.90); the 'delivery' scale showed a single domain (7 items, alpha=0.88).
      CFA in sample II confirmed both factor structures with an adequate model fit.
      Overall, satisfaction with care was highest among women who only received midwife
      led care, while women who were referred to an obstetrician during pregnancy
      reported less satisfaction. CONCLUSIONS: The 25-item PCQ, primarily based on the
      experiences and perceptions of pregnant women and women who recently gave birth,
      showed adequate psychometric properties evaluating the quality of care during
      pregnancy and delivery. This user-friendly instrument might be a valuable
      instrument for future research to further evaluate the quality of care to
      pregnant women.

PMID- 24332095
TI  - Breast cancer during pregnancy: a retrospective study on obstetrical problems and
      survival.
AB  - OBJECTIVES: Breast cancer is one of the most common cancers occurring in
      pregnancy. Data on survival of these patients and their obstetrical complications
      are still limited. STUDY DESIGN: We conducted a case-control, retrospective study
      to evaluate the overall survival (OS) of 22 patients with breast cancer in
      pregnancy (BCP) and 45 non-pregnant women with breast cancer (BC) matched for
      age, stage and hormonal status. RESULTS: Survival of BCP and BC patients using
      Kaplan-Meier analysis was similar (86.4% in cases and 80% in controls p=0.392)
      and BCP patients had survival consistent with the stage of the disease, providing
      that the treatment had been in agreement with the recommended protocols. The
      overall incidence of premature delivery was 54.6% and complications were observed
      in three newborns out of 23 (13%). CONCLUSIONS: Preterm labor induction without
      any obstetrical indication following woman's request to continue chemotherapy
      outside pregnancy can be reduced by explaining the risks of early delivery and
      the lack of effects of many chemotherapeutic regimens on the fetus.

PMID- 24332096
TI  - Hysteroscopic management of retained products of conception: meta-analysis and
      literature review.
AB  - OBJECTIVE: Hysteroscopic removal of retained products of conception (RPOC) may
      allow complete removal of RPOC and decreased rates of intrauterine adhesions
      (IUA) when compared to the traditional blind curettage. The aim of this meta
      analysis is to examine the current evidence regarding the use of hysteroscopy for
      treatment of RPOC. STUDY DESIGN: A literature search was conducted in December
      2012 using MEDLINE and ClinicalTrials. The study selection criteria were use of
      the standard hysteroscopic technique for removal of RPOC in 5 or more cases, in
      any study design. We reviewed 11 studies, of which 5 retrospective studies met
      the selection criteria (comprising 326 cases). The rates of incomplete RPOC
      removal, surgical complications, post-operative IUA and subsequent pregnancies
      were abstracted and weighted events rates using a fixed meta-analysis model were
      calculated. RESULTS: Only one study compared the rates of IUA following
      hysteroscopy and curettage, precluding a meta-analysis comparison of the two
      techniques. There were no cases of incomplete RPOC removal. Three perioperative
      complications occurred (uterine perforation, infection, and vaginal bleeding).
      IUA on follow-up hysteroscopy were found in 4/96 women (weighted rate of 5.7%,
      95% CI 2.4%, 13.0%). Of the 120 women desiring a subsequent pregnancy 91
      conceived (weighted rate of 75.3%, 95% CI 66.7%, 82.3%). CONCLUSIONS: The lack of
      traditional curettage comparison groups in most studies precludes the conclusion
      that hysteroscopy is superior to traditional curettage, but this procedure does
      appear to have low complication rates, low rates of IUA, and high rates of
      subsequent pregnancies.

PMID- 24332098
TI  - Alimentary satisfaction, gastrointestinal symptoms, and quality of life 10 or
      more years after esophagectomy with gastric pull-up.
AB  - OBJECTIVE: The aim of this study was to evaluate alimentary satisfaction,
      gastrointestinal symptoms, and quality of life >=10 years after esophagectomy
      with gastric pull-up. METHODS: Patients who had undergone esophagectomy with
      gastric pull-up before 2003 were interviewed regarding their alimentary function
      and completed the Gastrointestinal Quality of Life and RAND short-form, 36-item,
      questionnaires. RESULTS: We identified 67 long-term survivors after esophagectomy
      and gastric pull-up. Of these, 40 were located, and all agreed to participate.
      The median age was 75 years, and the median follow-up period was 12 years
      (interquartile range, 10-19). Most patients (88%) had no dysphagia, 90% were able
      to eat >=3 meals/day, and 93% finished >=50% of a typical meal. The mean
      alimentary comfort rating was 9 of 10. Dumping, diarrhea >=3 times/day, or
      regurgitation occurred in 33% of patients. Six patients (15%) had aspiration
      episodes requiring hospitalization. The median weight loss after surgery was 26
      lbs, and the current median body mass index was 25 kg/m(2). Only 2 patients were
      underweight (body mass index, <18.5 kg/m(2)). The median Gastrointestinal Quality
      of Life score was 2.9 of 4. The RAND scores were at the population mean in 1
      category (physical function) and above the normal mean in the remaining 7
      categories. CONCLUSIONS: Long-term nutritional status, quality of life, and
      satisfaction with eating were excellent after esophagectomy with gastric pull-up.
      Gastrointestinal side effects were common, but serious complications such as
      aspiration were uncommon. Pessimism regarding the long-term ability to enjoy a
      meal and live with a good quality of life after esophagectomy is unwarranted.

PMID- 24332097
TI  - Universal definition of perioperative bleeding in adult cardiac surgery.
AB  - OBJECTIVES: Perioperative bleeding is common among patients undergoing cardiac
      surgery; however, the definition of perioperative bleeding is variable and lacks
      standardization. We propose a universal definition for perioperative bleeding
      (UDPB) in adult cardiac surgery in an attempt to precisely describe and quantify
      bleeding and to facilitate future investigation into this difficult clinical
      problem. METHODS: The multidisciplinary International Initiative on Haemostasis
      Management in Cardiac Surgery identified a common definition of perioperative
      bleeding as an unmet need. The functionality and usefulness of the UDPB for
      clinical research was then tested using a large single-center, nonselected,
      cardiac surgical database. RESULTS: A multistaged definition for perioperative
      bleeding was created based on easily measured clinical end points, including
      total blood loss from chest tubes within 12 hours, allogeneic blood products
      transfused, surgical reexploration including cardiac tamponade, delayed sternal
      closure, and the need for salvage treatment. Depending on these components,
      bleeding is graded as insignificant, mild, moderate, severe, or massive. When
      applied to an established cardiac surgery dataset, the UDPB provided insight into
      the incidence and outcome of bleeding after cardiac surgery. CONCLUSIONS: The
      proposed UDPB in adult cardiac surgery provides a precise classification of
      bleeding that is useful in everyday practice as well as in clinical research.
      Once fully validated, the UDPB may be useful as an institutional quality measure
      and serve as an important end point in future cardiac surgical research.

PMID- 24332099
TI  - A "leaking" aorta.

PMID- 24332100
TI  - Discussion.

PMID- 24332101
TI  - Historical perspectives of The American Association for Thoracic Surgery: John H.
      Gibbon, Jr (1903-1973).

PMID- 24332103
TI  - How to size the main aortic endograft in a chimney procedure.

PMID- 24332102
TI  - Balancing curability and unnecessary surgery in the context of computed
      tomography screening for lung cancer.
AB  - OBJECTIVE: Surgical management is a critical component of computed tomography
      (CT) screening for lung cancer. We report the results for US sites in a large
      ongoing screening program, the International Early Lung Cancer Action Program (I
      ELCAP). METHODS: We identified all patients who underwent surgical resection. We
      compared the results before (1993-2005) and after (2006-2011) termination of the
      National Lung Screening Trial to identify emerging trends. RESULTS: Among 31,646
      baseline and 37,861 annual repeat CT screenings, 492 patients underwent surgical
      resection; 437 (89%) were diagnosed with lung cancer; 396 (91%) had clinical
      stage I disease. In the 54 (11%) patients with nonmalignant disease, resection
      was sublobar in 48 and lobectomy in 6. The estimated cure rate based on the 15
      year Kaplan-Meier survival for all 428 patients (excluding 9 typical carcinoids)
      with lung cancer was 84% (95% confidence interval [CI], 80%-88%) and 88% (95% CI,
      83%-92%) for clinical stage I disease resected within 1 month of diagnosis. Video
      assisted thoracoscopic surgery and sublobar resection increased significantly,
      from 10% to 34% (P < .0001) and 22% to 34% (P = .01) respectively; there were no
      significant differences in the percentage of malignant diagnoses (90% vs 87%, P =
      .36), clinical stage I (92% vs 89%, P = .33), pathologic stage I (85% vs 82%, P =
      .44), tumor size (P = .61), or cell type (P = .81). CONCLUSIONS: The frequency
      and extent of surgery for nonmalignant disease can be minimized in a CT screening
      program and provide a high cure rate for those diagnosed with lung cancer and
      undergoing surgical resection.

PMID- 24332104
TI  - Antegrade thoracic stent grafting during repair of acute Debakey type I
      dissection promotes distal aortic remodeling and reduces late open distal
      reoperation rate.
AB  - OBJECTIVE: Previously, we showed that antegrade stent grafting of the descending
      thoracic aorta during DeBakey type I dissection repair improves distal aortic
      remodeling. We assessed midterm outcomes of this reconstructive strategy compared
      with standard open repair. METHODS: DeBakey type I dissections (non-Marfan,
      nontotal arch cases only) from 2005 to 2012 were retrospectively reviewed. One
      hundred eighty patients underwent standard open repair (standard group), and 62
      patients underwent open repair plus stenting (stented group). Open repair
      entailed ascending aorta plus transverse hemiarch reconstruction under
      circulatory arrest, with variable aortic root work. Data was prospectively
      maintained. RESULTS: Preoperative parameters were similar. Patients in the
      stented group had longer circulatory arrest time and higher utility of antegrade
      cerebral perfusion (P < .001). In-hospital/30-day mortality (10% vs 14%; P =
      .51), stroke (5% vs 8%; P = .6), and paraplegia (0% vs 1%; P = 1) were similar in
      the stented versus standard groups. Mean follow-up was 2.7 +/- 2.3 and 2.2 +/-
      2.1 years. Actuarial survival in stented versus standard groups at 1 and 7 years
      was 86% versus 81% and 76% versus 60% (P = .5). Thoracic aorta false lumen
      obliteration was improved in the stented group (82% vs 39%; P < .001), along with
      improved freedom from open distal aortic reoperation rate (98% vs 90% at 6 years,
      P = .1). Endovascular distal aortic reintervention rate was higher in the stented
      group (18% vs 3%; P = .008), with zero mortality. CONCLUSIONS: Antegrade stent
      graft deployment during acute DeBakey type I dissection repair is safe method to
      promote distal aortic remodeling without increasing postoperative or midterm
      mortality. This technique provides increased freedom from open distal aortic
      reoperations compared with standard open repair.

PMID- 24332105
TI  - Quantitative analysis of 3-dimensional aortic annular geometry: implication for
      aortic root reimplantation.

PMID- 24332106
TI  - Effect of severe acidosis on vasoactive effects of epinephrine and norepinephrine
      in human distal mammary artery.
AB  - OBJECTIVE: Acidosis is a very common pathologic process in perioperative
      management. However, how to correct severe acidosis to improve the efficacy of
      vasoconstrictors in hemodynamically unstable patients is still debated. The
      present study investigated whether severe extracellular acidosis influences the
      vasoactive properties of vasoconstrictors on human isolated arteries. METHODS:
      Segments of intact distal internal mammary arteries were removed from 41 patients
      undergoing artery bypass grafting. The arterial rings were washed in Krebs
      Henseleit solution and suspended in an organ bath. The rings were set at a
      pretension equivalent of 100 mm Hg, and the relaxation response to 10 MUM
      acetylcholine was verified. Concentration-response curves for epinephrine,
      norepinephrine, methoxamine (alpha1A/D-adrenoceptor agonist), phenylephrine
      (equipotent agonist of alpha1A/B-adrenoceptors), and clonidine (alpha2
      adrenoceptor agonist) were achieved under control conditions (pH 7.40) and under
      acidic conditions by substitution of the Krebs-Henseleit solution with a modified
      solution. RESULTS: Decreasing the pH from 7.40 to 7.20, 7.0, or 6.80 did not
      significantly alter the potency and efficacy of epinephrine and norepinephrine,
      although the standardized effect size was sometimes large. Severe acidosis (pH
      6.80) did not significantly change the potency and efficacy of phenylephrine and
      clonidine, although it increased the efficacy and potency of methoxamine (P <
      .001 and P = .04 vs paired control conditions, respectively). CONCLUSIONS:
      Extracellular acidosis did not impair the vasoactive properties of epinephrine
      and norepinephrine in human medium-size arteries until pH 6.80. The results of
      the present study also suggest that acidosis might potentiate arterial
      responsiveness to vasoconstrictors, mostly by way of the alpha1D-adrenoceptor.

PMID- 24332107
TI  - Similar cerebral protective effectiveness of antegrade and retrograde cerebral
      perfusion combined with deep hypothermia circulatory arrest in aortic arch
      surgery: a meta-analysis and systematic review of 5060 patients.
AB  - OBJECTIVE: Our objective was to determine if antegrade cerebral perfusion (ACP)
      and retrograde cerebral perfusion (RCP) combined with deep hypothermia
      circulatory arrest in aortic arch surgery results in different mortality and
      neurologic outcomes. METHODS: The Cochrane Library, Medline, EMBASE, CINAHL, Web
      of Science, and the Chinese Biomedical Database were searched for studies
      reporting on postoperative strokes, permanent neurologic dysfunction, temporary
      neurologic dysfunction, and all causes mortality within 30 days postoperation in
      aortic arch surgery. Meta-analysis for effect size, t test, and I(2) for
      detecting heterogeneity and sensitivity analysis for assessing the relative
      influence of each study was performed. RESULTS: Fifteen included studies
      encompassed a total of 5060 patients of whom 2855 were treated with deep
      hypothermic circulatory arrest plus ACP and 1897 were treated with deep
      hypothermic circulatory arrest plus RCP. Pooled analysis showed no significant
      statistical difference (P > .01) of 30-day mortality, permanent neurologic
      dysfunction, and transient neurologic dysfunction in the 2 groups. Before
      sensitivity analysis, postoperative stroke incidence in the ACP group was higher
      than in the RCP group (7.2% vs 4.7%; P < .01). After a study that included a
      different percentage of patients with a history of central neurologic events in
      the 2 groups was ruled out, postoperative stroke incidence in the 2 groups also
      showed no significant statistical difference (P > .01). CONCLUSIONS: ACP and RCP
      provide similar cerebral protective effectiveness combined with deep hypothermia
      circulatory arrest and could be selected according to the actual condition in
      aortic arch surgery. A high-quality randomized controlled trial is urgently
      needed to confirm this conclusion, especially for stroke morbidity following ACP
      or RCP.

PMID- 24332108
TI  - Stented bovine jugular vein graft (Melody valve) for surgical mitral valve
      replacement in infants and children.
AB  - OBJECTIVE: The options for mitral valve replacement in children with irreparable
      mitral valve disease have been limited to fixed-diameter prostheses that do not
      accommodate for somatic growth. We have modified an externally stented bovine
      jugular vein graft (Melody valve) for implantation in this cohort. Because it is
      not a fixed-diameter prosthesis, we hypothesized that the valve can be expanded
      in the catheterization laboratory as the child grows. METHODS: The medical
      records of patients who had undergone Melody valve implantation in the mitral or
      left atrioventricular valve position from 2010 to 2013 were reviewed. RESULTS:
      Eleven patients had undergone Melody valve implantation at a median age of 7
      months (range, 2-28). The techniques of valve modification and implantation
      included stent shortening, adding a pericardial sewing cuff, intraoperative
      balloon expansion, and fixation of the distal stent to the inferior left
      ventricle wall. The valve was competent, with a low gradient acutely
      postoperatively in all patients. One patient died, and one required permanent
      pacemaker implantation. One patient developed valve dysfunction and required
      explantation. Two patients without a pericardial sewing cuff developed
      paravalvular leaks. One patient who had not undergone distal stent fixation
      developed left ventricular outflow tract obstruction. Three patients who had
      undergone subsequent catheter-based balloon expansion of the valve have continued
      to demonstrate acceptable valvular function. CONCLUSIONS: The Melody valve has
      demonstrated acceptable short-term function. Implantation techniques to prevent
      left ventricular outflow tract obstruction (suture fixation of the distal stent)
      and paravalvular leaks (the addition of a pericardial cuff) should be considered.
      The Melody valve can be percutaneously expanded as the child grows.

PMID- 24332109
TI  - Transfusion practice varies widely in cardiac surgery: Results from a national
      registry.
AB  - OBJECTIVES: Evidence is accumulating of adverse outcomes associated with
      transfusion of blood components. If there are differences in perioperative
      transfusion rates in cardiac surgery, and what hospital factors may contribute,
      requires further investigation. METHODS: Analysis of 42,743 adult patients who
      underwent 43,482 procedures from 2005 to 2011 at 25 Australian hospitals,
      according to the Australian and New Zealand Society of Cardiac and Thoracic
      Surgeons Cardiac Surgery Database. Multiple logistic regression examined
      associations of patient and hospital characteristics with transfusion of >=1 red
      blood cell (RBC) unit; platelet (PLT), fresh frozen plasma (FFP), and
      cryoprecipitate (CRYO) doses; and >=5 RBC units, from surgery until hospital
      discharge. RESULTS: Procedures included 24,222 (55%) isolated coronary artery
      bypass grafts, 7299 (17%) isolated valve, 4714 (11%) coronary artery bypass graft
      and valve, and 7247 (17%) other procedures. After adjustment for various patient
      and procedure characteristics, transfusion rates varied across hospitals for >=1
      RBC unit from 22% to 67%, >=5 RBC units from 5% to 25%, >=1 PLT dose from 11% to
      39%, >=1 FFP dose from 11% to 48% and >=1 CRYO dose from 1% to 20%. Hospital
      characteristics, including state or territory, private versus public, and
      teaching versus nonteaching, were not associated with variation in transfusion
      rates. CONCLUSIONS: Variation in transfusion of all components and large volume
      RBC was identified, even after adjustment for patient and procedural factors
      known to influence transfusion, and this was not explained by hospital
      characteristics.

PMID- 24332111
TI  - Unidirectional valved patch closure of ventricular septal defects with severe
      pulmonary arterial hypertension: hemodynamic outcomes.
AB  - OBJECTIVE: The purpose of the present study was to study the midterm hemodynamic
      outcomes of unidirectional valved patch closure of ventricular septal defects
      (VSDs) in patients with VSD and pulmonary arterial hypertension (PAH). METHODS:
      From January 2006 to January 2012, 20 patients with VSD with PAH and a pulmonary
      vascular resistance index >8 Wood units underwent VSD closure with a
      unidirectional valved patch using the technique previously described by us. Of
      these, 13 patients agreed to follow-up cardiac catheterization and were studied
      at a mean follow-up of 34.7 +/- 18.6 months (range, 2-56). The mean age of these
      13 patients was 8.5 +/- 4.4 years (range, 2-19; median, 9), and the mean
      preoperative systemic saturation was 94.1% +/- 3.4% (range, 87-99; median, 95.0)
      The mean preoperative pulmonary artery systolic pressure was 96.2 +/- 13.6 mm Hg
      (range, 75-115; median, 103.0), and the mean preoperative pulmonary vascular
      resistance index was 10.0 +/- 2.1 Wood units (range, 8.0-15.1; median, 9.3).
      RESULTS: At follow-up cardiac catheterization, the mean systemic saturation had
      increased to 98.92%. The pulmonary vascular resistance index had decreased
      significantly to 5.8 +/- 2.1 Wood units (P = .02). A significant decrease was
      seen in the pulmonary artery systolic, diastolic, and mean pressures (P = .000),
      and none of the patients had severe PAH. No patients died, and all patients were
      in New York Heart Association class I. CONCLUSIONS: Unidirectional valved patch
      closure of VSD is a promising technique for patients with a large VSD and severe
      PAH. It had a favorable effect on the immediate, early, and midterm clinical
      outcomes and hemodynamic parameters.

PMID- 24332112
TI  - Single center experience with the Sorin Bicarbon prosthesis: a 17-year clinical
      follow-up.
AB  - OBJECTIVE: To evaluate the long-term results of aortic valve replacement (AVR)
      and mitral valve replacement (MVR) with the Sorin Bicarbon prosthesis (SBP).
      METHODS: Five hundred seven patients (306 men, 201 women), mean age 62+/-10 years
      (range, 21-86 years), received an SBP between 1994 and 2000; AVR was performed in
      344 (67%) and MVR in 163 (33%). The main concomitant procedure was coronary
      artery grafting in 79 patients (16%). Follow-up was 99% complete; mean follow-up
      was 12.7+/-4.0 years with a cumulative duration of follow-up of 6475 patient
      years in the entire group (4348 patient-years for AVR and 2124 patient-years for
      MVR). RESULTS: Hospital mortality was 2.7% (AVR, 2.03%; MVR, 4.3%). There were
      169 late deaths (AVR, 128; MVR, 41). Actuarial survival at 17 years is 49.7%+/
      5.3% for AVR and 62.0%+/-6.1% for MVR. At the last follow-up, 310 survivors (199
      AVR, 111 MVR) are in New York Heart Association functional class I or II. At 17
      years, actuarial freedom from valve-related deaths, embolism, and bleeding is
      89.8%+/-4.8%, 85.8%+/-5.4%, and 96.2%+/-1.2% after AVR, and 91.9%+/-3.9%, 96.3%+/
      1.8%, 95.0%+/-2.9% after MVR. Reoperation was required in 5 patients with AVR
      (thrombosis in 4 and perivalvular leak in 1). Actuarial freedom from reoperation
      is 98.1%+/-0.8% after AVR and 100% after MVR; freedom from endocarditis is 100%
      after AVR and 99.2%+/-0.7% after MVR. No cases of intrinsic structural valve
      failure were observed. CONCLUSIONS: The SBP has shown excellent results in terms
      of clinical improvement and freedom from valve-related complications, even up to
      17 years after AVR and MVR. It therefore seems to be a safe option whenever a
      mechanical prosthesis is needed.

PMID- 24332110
TI  - Minimally invasive fibrillating mitral valve replacement for patients with
      advanced cardiomyopathy: a safe and effective approach to treat a complex
      problem.
AB  - OBJECTIVE: The optimal management of mitral regurgitation (MR) in patients with
      cardiomyopathy has been controversial. Minimally invasive fibrillating mitral
      valve replacement (mini-MVR) might limit postoperative morbidity and mortality by
      minimizing recurrent MR. We hypothesized that mini-MVR with complete chordal
      sparing would offer low mortality and halt left ventricular (LV) remodeling in
      patients with severe cardiomyopathy and severe MR. METHODS: From January 2006 to
      August 2009, 65 patients with an LV ejection fraction (LVEF) of <=35% underwent
      mini-MVR. The demographic, echocardiographic, and clinical outcomes were
      analyzed. RESULTS: The operative mortality compared with the Society of Thoracic
      Surgeons-predicted mortality was 6.2% versus 6.6%. It was 5.6% versus 7.4% for
      patients with an LVEF of <=20% and 8.3% versus 17.9% among patients with a
      Society of Thoracic Surgeons-predicted mortality of >=10%. At a median follow-up
      of 17 months, no recurrent MR or change in the LV dimensions or LVEF had
      developed, but the right ventricular systolic pressure had decreased (P=.02). At
      the first postoperative visit and latest follow-up visit, the New York Heart
      Association class had decreased from 3.0+/-0.6 to 1.7+/-0.7 and 2.0+/-1.0,
      respectively (P<.0001 for both). Patients with an LVEF of <=20% and LV end
      diastolic diameter of >=6.5 cm were more likely to meet a composite of death,
      transplantation, or LV assist device insertion (P=.046). CONCLUSIONS: Our results
      have shown that mini-MVR is safe in patients with advanced cardiomyopathy and
      resulted in no recurrent MR, stabilization of the LVEF and LV dimensions, and a
      decrease in right ventricular systolic pressure. This mini-MVR technique can be
      used to address severe MR in patients with advanced cardiomyopathy.

PMID- 24332113
TI  - Long-term outcomes after elective isolated mechanical aortic valve replacement in
      young adults.
AB  - OBJECTIVES: The aim of this study was to determine long-term survival and
      clinical outcomes after elective isolated mechanical aortic valve replacement in
      young adults. METHODS: A clinical observational study was conducted in a cohort
      of 450 consecutive adults less than 65 years of age who had undergone elective
      isolated mechanical aortic valve replacement (AVR) between 1997 and 2006.
      Patients who had undergone previous cardiac surgery, and those undergoing
      concomitant procedures or urgent surgery were excluded. Follow-up was 93.3%
      complete with a mean follow-up of 9.1+/-3.5 years. The primary end point was
      survival. Life table analyses were used to determine age- and gender-matched
      general population survival. Secondary end points were reoperation and valve
      related complications. RESULTS: Overall actuarial survival at 1, 5, and 10 years
      was 98%+/-1%, 95%+/-1%, and 87%+/-1%, respectively, which was lower than expected
      in the age- and gender-matched general population in Quebec. Actuarial freedom
      from prosthetic valve dysfunction was 99%+/-0.4%, 95%+/-1%, and 91%+/-1% at 1, 5,
      and 10 years, respectively. Actuarial freedom from valve reintervention was 98%+/
      1%, 96%+/-1%, and 94%+/-1% at 1, 5 and 10 years, respectively. Actuarial survival
      free from reoperation at 10 years was 82%+/-2%. Actuarial freedom from major
      hemorrhage was 98%+/-1%, 96%+/-1%, and 90%+/-2% at 1, 5, and 10 years,
      respectively. CONCLUSIONS: In young adults undergoing elective isolated
      mechanical AVR, survival remains suboptimal compared with an age- and gender
      matched general population. Furthermore, there is a low but constant hazard of
      prosthetic valve reintervention after mechanical AVR.

PMID- 24332114
TI  - Early and midterm outcomes of left pulmonary artery angioplasty using an anterior
      wall flap of the main pulmonary artery in tetralogy of Fallot repair.
AB  - OBJECTIVES: Postoperative left pulmonary artery (LPA) kinking is problematic in
      repair of tetralogy of Fallot (TOF). We used angioplasty of the proximal LPA with
      an anterior wall flap of the main pulmonary artery (MPA) to prevent this problem.
      METHODS: We have used an anterior wall of the MPA as a flap for LPA angioplasty
      in 42 patients with TOF and pulmonary stenosis (26 males and 16 females) since
      February 2007. During the same period, 116 patients underwent total repair of TOF
      with pulmonary stenosis. The median age was 7.1 months (range, 3-88.8), and the
      median weight was 8.4 kg (range, 5-27). The indications for LPA angioplasty were
      acute-angle proximal LPA in 17 (40.5%), proximal LPA stenosis in 6 (14.3%), acute
      angle and stenotic proximal LPA in 18 (43%), and short and small distal MPA in 1
      patient. The patches used for MPA and LPA reconstruction were glutaraldehyde
      treated autologous pericardium in 34 and bovine pericardium in 8 patients.
      RESULTS: No operative or late death occurred. The mean follow-up duration after
      surgery was 26.4 +/- 18.6 months (range, 0.5-67). During the follow-up period,
      reoperation for LPA stenosis or kinking was not required in any patient; however,
      balloon angioplasty was performed with good results in 4 patients (9.5%). No
      postoperative kinking of the proximal LPA occurred. Echocardiography or computed
      tomography angiography at the recent follow-up visit demonstrated good branch
      pulmonary arteries in all patients. CONCLUSIONS: Angioplasty of the proximal LPA
      using an anterior wall flap of the MPA in the patients with TOF and pulmonary
      stenosis is an effective method in the management of acute angle and/or stenosis
      of LPA without postoperative kinking.

PMID- 24332115
TI  - Fate of functional tricuspid regurgitation in aortic stenosis after aortic valve
      replacement.
AB  - OBJECTIVE: Functional tricuspid regurgitation (TR) is found not infrequently in
      conjunction with aortic stenosis. The aim of the present study was to evaluate
      the changes in TR and to identify the predictors of late progression after aortic
      valve replacement. METHODS: We evaluated 354 patients who had undergone aortic
      valve replacement for aortic stenosis from January 1995 to December 2009.
      Patients with mitral regurgitation were excluded. Of the 354 patients, 54 had TR
      greater than mild. The mean follow-up duration was 4.4+/-4.3 years (maximum, 15).
      The serial echocardiographic and clinical data were analyzed. RESULTS: No early
      mortality occurred, and the late cardiac mortality rate was 3.9% (14 of 354). In
      the 48 patients with TR greater than mild, TR did not improve in 23 (49.1%)
      during the follow-up period. Freedom from cardiac mortality at 10 years was lower
      in those with TR greater than mild than in patients without TR (61.6%+/-16.7% vs
      93.0%+/-2.9%, P=.008). Left ventricular diastolic function correlated with right
      ventricular systolic pressure (P<.001) and the degree of TR during follow-up
      (P=.001). Multivariate analysis showed that postoperative atrial fibrillation
      (odds ratio, 6.8; P=.001) and the aortic transprosthetic mean pressure gradient
      (odds ratio, 1.1; P=.028) predicted late TR greater than mild. CONCLUSIONS: Not
      only did TR in patients with aortic stenosis frequently persist after aortic
      valve replacement, it was progressive in some. This finding was associated with
      left ventricular diastolic dysfunction. A concomitant tricuspid valve procedure
      could be considered in selected patients with aortic stenosis to avoid late TR.

PMID- 24332118
TI  - Primary prevention of type 2 diabetes by lifestyle intervention in primary care
      setting.

PMID- 24332117
TI  - Reliability of joint count assessment in rheumatoid arthritis: a systematic
      literature review.
AB  - BACKGROUND: Joint counts are central to the assessment of rheumatoid arthritis
      (RA) but reliability is an issue. OBJECTIVES: To evaluate the reliability and
      agreement of joint counts (intra-observer and inter-observer) by health care
      professionals (physicians, nurses, and metrologists) and patients in RA, and the
      impact of training and standardization on joint count reliability through a
      systematic literature review. METHODS: Articles reporting joint count reliability
      or agreement in RA in PubMed, EMBase, and the Cochrane library between 1960 and
      2012 were selected. Data were extracted regarding tender joint counts (TJCs) and
      swollen joint counts (SJCs) derived by physicians, metrologists, or patients for
      intra-observer and inter-observer reliability. In addition, methods and effects
      of training or standardization were extracted. Statistics expressing reliability
      such as intraclass correlation coefficients (ICCs) were extracted. Data analysis
      was primarily descriptive due to high heterogeneity. RESULTS: Twenty-eight
      studies on health care professionals (HCP) and 20 studies on patients were
      included. Intra-observer reliability for TJCs and SJCs was good for HCPs and
      patients (range of ICC: 0.49-0.98). Inter-observer reliability between HCPs for
      TJCs was higher than for SJCs (range of ICC: 0.64-0.88 vs. 0.29-0.98). Patient
      inter-observer reliability with HCPs as comparators was better for TJCs (range of
      ICC: 0.31-0.91) compared to SJCs (0.16-0.64). Nine studies (7 with HCPs and 2
      with patients) evaluated consensus or training, with improvement in reliability
      of TJCs but conflicting evidence for SJCs. CONCLUSION: Intra- and inter-observer
      reliability was high for TJCs for HCPs and patients: among all groups,
      reliability was better for TJCs than SJCs. Inter-observer reliability of SJCs was
      poorer for patients than HCPs. Data were inconclusive regarding the potential for
      training to improve SJC reliability. Overall, the results support further
      evaluation for patient-reported joint counts as an outcome measure.

PMID- 24332119
TI  - Patient communication competence: development of a German questionnaire and
      correlates of competent patient behavior.
AB  - OBJECTIVE: The aim of our study was to design and psychometrically test a patient
      questionnaire to capture patient communication competence in the context of
      patient-provider interaction (CoCo questionnaire). We also aimed to determine
      patient characteristics associated with competent patient behavior. METHODS: To
      assure content validity, we initially conducted 17 focus groups (n=97) made up of
      patients and providers. In the main study n=1.264 patients with chronic back
      pain, chronic-ischemic heart disease or breast cancer who underwent inpatient
      rehabilitation were surveyed at the end of rehabilitation. RESULTS: The CoCo
      questionnaire contains four scales (patient adherence in communication, critical
      and participative communication, communication about personal circumstances,
      active disease-related communication) and 28 items addressing competent patient
      behavior. We provide evidence of unidimensionality, local independence,
      reliability, a Rasch-Model fit, the absence of differential item functioning, and
      signs of construct validity. The most important correlates of communication
      competence are health literacy and communication self-efficacy. CONCLUSION: The
      CoCo questionnaire has good psychometric properties in German. Future research
      should examine CoCo's responsiveness and analyze criterion validity by means of
      observation data. PRACTICE IMPLICATIONS: The CoCo questionnaire can be
      recommended for use in evaluating patient communication training programs.

PMID- 24332120
TI  - Pulmonary artery rupture during Swan-Ganz catheterisation: a case report.
AB  - Catheter-induced pulmonary artery rupture is an infrequent complication that may
      occur during invasive cardiopulmonary monitoring. Fatal cases are uncommon and
      result from hemoptysis and flooding of the opposite lung with resulting hypoyxia.
      Alpha-1-antitrypsin deficiency is a rare genetic disorder characterised by low
      serum levels of alpha-1-antitrypsin, critical in maintaining connective tissue
      integrity. Besides pulmonary emphysema, recent observations suggest that alpha-1
      antitrypsin deficiency may also be involved in vascular wall weakening, thereby
      predisposing arteries to dissection and aneurysm formation. In this article, we
      describe an autopsy case of pulmonary artery iatrogenic rupture due to insertion
      of a Swan-Ganz catheter in an 82-year-old woman suffering from pulmonary
      hypertension and alpha-1-antitrypsin deficiency. The exact source of bleeding
      could not be precisely identified during autopsy due to the extent of tissue
      hemorrhage, though postmortem angiography revealed a contrast medium
      extravasation from a branch of the left pulmonary lower lobar artery. The case
      herein emphasises the importance of postmortem angiography in facilitating the
      detection of vascular injuries, the importance of familiarity with intensive care
      techniques and procedures on behalf of forensic pathologists as well as in-depth
      knowledge of all possible contributing conditions and predisposing disorders in
      the pathogenesis of death. 

PMID- 24332116
TI  - Lupus mesenteric vasculitis: clinical features and associated factors for the
      recurrence and prognosis of disease.
AB  - OBJECTIVE: To evaluate the clinical characteristics of lupus mesenteric
      vasculitis (LMV) and identify the potential factors and appropriate treatments
      that are associated with disease relapse and prognosis in LMV. METHODS: A
      retrospective cohort study was performed among patients admitted to the First
      Affiliated Hospital of Sun Yet-sen University between 2002 and 2011. Demographic
      information, clinical symptoms, laboratory findings, imaging characteristics like
      abdominal CT scan, ultrasonography, medications including corticosteroid,
      cyclophosphamide, and other immunosuppressive agents, and outcomes were
      documented. The endpoints of the study were defined as occurrence of severe
      complications that needed surgical intervention, disease recurrence, or death.
      RESULTS: Out of 3823 systemic lupus erythematosus (SLE) patients, 97 were
      diagnosed with mesenteric vasculitis with the overall prevalence of 2.5%. Among
      these 97 LMV patients, 13 died because of serious complications (13/97, 13.4%)
      and 2 presented intestinal perforation during the induction therapy stage. The
      logistic regression multivariate analysis indicated that leukopenia [peripheral
      WBC, odds ratio (OR) = 0.640, 95% confidence interval (CI): 0.456-0.896, P =
      0.009], hypoalbuminemia (serum albumin, OR = 0.891, 95% CI: 0.798-0.994, P =
      0.039) and elevated serum amylase (OR = 7.719, 95% CI: 1.795-33.185, P = 0.006)
      were positively associated with the occurrence of serious complications, while
      intravenous cyclophosphamide (CYC) therapy inhibited the occurrence of serious
      complications (OR = 0.220, 95% CI: 0.053-0.903, P = 0.036). A total of 79
      patients who achieved remission were followed-up for 2-96 months and 18 cases
      experienced disease relapse (18/79, 22.8%). The statistical analysis adjusted by
      Cox proportional hazards models indicated that high-dose CYC therapy (>= 1.0
      g/m(2)/month) was a protective factor for disease relapse and led to better
      outcomes [hazard ratio (HR) = 0.209, 95% CI: 0.049-0.887, P = 0.034], while the
      severe thickness of the bowel wall (>8mm) was a risk factor (HR = 7.308, 95% CI:
      1.740-30.696, P = 0.007). LMV and lupus cystitis occurred concurrently in 22
      (22/97, 22.7%) patients, and the symptoms of urinary tract resolved after
      treatment with corticosteroid and immunosupressants. CONCLUSION: LMV is one of
      the serious complications of SLE with high mortality. The current study
      demonstrated that leukopenia, hypoalbuminemia, and elevated serum amylase were
      associated with severe adverse events, while CYC therapy led to better outcomes
      during remission-induction stage. Severe thickness of the bowel was a risk factor
      while high-dose CYC therapy was a protective factor for disease relapse in
      intensification therapy stage. It is necessary to evaluate the urinary tract
      involvement once LMV is diagnosed due to the frequent coexistence of these 2
      diseases.

PMID- 24332127
TI  - [Give attention to new technique of radiotherapy and its application in
      gynecological malignancy].

PMID- 24332123
TI  - Progression of lower urinary tract symptoms after discontinuation of 1 medication
      from 2-year combined alpha-blocker and 5-alpha-reductase inhibitor therapy for
      benign prostatic hyperplasia in men--a randomized multicenter study.
AB  - OBJECTIVE: To investigate the treatment outcome of discontinuing 1 medication
      from 2-year combination therapy for male benign prostatic hyperplasia/lower
      urinary tract symptoms. MATERIALS AND METHODS: Patients with International
      Prostate Symptom Score >= 8, total prostatic volume (TPV) >30 mL, and maximum
      flow rate (Qmax) <15 mL/s were randomly assigned to the 5alpha-reductase
      inhibitor (5ARI) discontinue (DC-5ARI) or alpha-blocker discontinue (DC-alpha
      blocker) group. All patients received combination therapy with dutasteride (0.5
      mg QD) and doxazosin (4 mg QD) for 2 years and then discontinued either one drug
      for 12 months. The primary endpoint was the occurrence of resuming medication.
      The secondary endpoints were the net parameters changed or the need of
      transurethral resection of the prostate (TURP). RESULTS: A total of 117 patients
      in DC-5ARI and 113 in DC-alpha-blocker group completed the study. The baseline
      TPV and Qmax were similar between groups before combination therapy. Resumption
      of combination therapy was significantly more in DC-5ARI than DC-alpha-blocker
      group (51.3% vs 31.0%; P = .005). The mean duration from discontinuing to
      resuming medication was 5.0 +/- 4.4 months in DC-alpha-blocker and 7.8 +/- 3.8
      months in DC-5ARI group (P <.05). The TPV progression (29.1% vs 8.0%; P <.001)
      and the need for TURP (14.5% vs 7.1%; P = .043) were significantly higher in DC
      5ARI than DC-alpha-blocker group. Patients with larger TPV (45.8 +/- 18.1 mL) had
      significantly greater need for resuming 5ARI than smaller TPV (36.3 +/- 16.9 mL;
      P = .007), and a lower Qmax might predict resuming alpha-blocker. CONCLUSION:
      After a 2-year combination therapy, discontinuation of either one drug induced
      benign prostatic hyperplasia progression in either group. Greater risk of
      resuming medication and needing TURP were noted in patients who discontinued
      5ARI.

PMID- 24332121
TI  - Clinical trial design for the development of new therapies for nonmuscle-invasive
      bladder cancer: report of a Food and Drug Administration and American Urological
      Association public workshop.
AB  - OBJECTIVE: To summarize the discussion at a public workshop, cosponsored by the
      U.S. Food and Drug Administration (FDA) and the American Urological Association,
      reviewing potential trial designs for the development of new therapies for non
      muscle-invasive bladder cancer (NMIBC). There have been only 3 drug approvals for
      NMIBC in the last 30 years, and product development for this disease has been
      stymied by difficulties in trial design and patient accrual. METHODS: A workshop
      evaluating potential trial design for the development of therapies for NMIBC was
      held in San Diego, CA, in May 2013. Invited experts representing all
      stakeholders, including urology, medical oncology, radiation oncology, industry,
      and patient advocates, discussed development of products for all risk strata of
      NMIBC. RESULTS: The panel responded to specific questions from the FDA,
      discussing eligibility criteria, efficacy endpoints, and trial design for
      patients with a mix of high-grade papillary disease and carcinoma in situ,
      Bacillus Calmette-Guerin (BCG)-refractory disease, and intermediate-risk disease.
      Panel members also addressed the magnitude of response that would be clinically
      meaningful for various disease strata and trial design options for perioperative
      intravesical chemotherapy instillation at the time of resection of bladder
      tumors. CONCLUSION: Expert commentary provided by panel members will inform a
      planned FDA guidance on pathways for drug and biologic development for NMIBC and
      will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee.
      FDA intends to develop a set of principles that can be used to promote the
      development of new products for this disease.

PMID- 24332124
TI  - Editorial comment.

PMID- 24332128
TI  - [Prognostic analysis of radical radiotherapy in stage Ib and IIa cervical
      carcinoma].
AB  - OBJECTIVE: To investigate the efficacy and prognostic factors in patients with
      stage Ib and IIa cervical carcinoma by radical radiotherapy. METHODS: Between
      January 1999 and January 2012, 108 patients with stage Ib and IIa cervical
      carcinoma received radical radiotherapy in Cancer Hospital, Chinese Academy of
      Medical Sciences were included and analyzed retrospectively. Patients of stage
      Ib1, Ib2, IIa1 and IIa2 were 18 (16.7%, 18/108), 38 (35.2%, 38/108), 33 (30.6%,
      33/108) and 19 (17.6%, 19/108), respectively. RESULTS: The 5-year overall
      survival rate was 76.2% and the 5-year disease free survival rate was 75.6%.
      Totally 25 (23.1%, 25/108) patients developed recurrent disease, 16 of them (64%,
      16/25) had local recurrences, 6 (24%, 6/25) had distant metastases and 3 cases
      had both local recurrence and distant metastases. Among patients with recurrent
      disease, 23 died and 2 survive with tumor. Totally 24 patients died, 23 of them
      died due to tumor recurrence and the other one died of other reason. The
      univariate analysis showed that, lymph node metastasis, squamous cell carcinoma
      antigen (SCC) levels before treatment, SCC levels after treatment 1 month had
      relation with overall survival time in patients with stage Ib and IIa cervical
      carcinoma (all P < 0.05). The multivariate analysis showed that, lymph node
      metastasis and SCC levels after treatment 1 month were the independent prognostic
      factors for overall survival time for the cervical squamous cell carcinoma (OR =
      2.5, 4.4; all P < 0.05). CONCLUSIONS: By means of radical radiotherapy, stageIb
      and IIa cervical carcinoma patients with lymph node metastasis and SCC levels >=
      1.5 mg/L after treatment one month have poor prognosis.While, stageIb and IIa
      patients with concurrent chemoradiotherapy after neoadjuvant chemotherapy did not
      affect the prognosis. The 5-year survival rate with concurrent chemoradiotherapy
      was higher than that of radiotherapy.

PMID- 24332125
TI  - Editorial comment.

PMID- 24332129
TI  - [Extended-field intensity modulated radiation therapy and intra-cavitary
      brachytherapy combined with chemotherapy for stage Ib1-IVa cervical cancer with
      positive para-aortic lymph nodes].
AB  - OBJECTIVE: To investigate the treatment effects and toxicities of extended-field
      intensity modulated radiation therapy (EF-IMRT) and intra-cavitary brachytherapy
      combined with chemotherapy for stageIb1-IVa cervical cancer with positive para
      aortic lymph nodes. METHODS: A total of 46 stage Ib1-IVa cervical cancer patients
      with positive para-aortic lymph nodes treated at Fudan University Shanghai Cancer
      Center between 2009 and 2011 were reviewed. Neoadjuvant, concomitant and adjuvant
      chemotherapy with paclitaxel and carboplatin were administrated for one cycle
      before radiation therapy, two cycles during radiation therapy or three cycles
      after radiation therapy. All patients received EF-IMRT and intra-cavitary
      brachytherapy. The positive lymph nodes received an additional boost dose.
      RESULTS: All patients received EF-IMRT to 50.4 Gy (1.8 Gy per fraction). Twenty
      six patients was treated with boost dose of 6.0-8.0 Gy in 2.0 Gy per fraction to
      positive para-aortic lymph nodes. Thirty-seven patients received a positive para
      aortic lymph nodes boost or (and) parametrial boost. All patient also received a
      high-dose-rate intra-cavitary brachytherapy at the point "A" dose of 20.0-30.0 Gy
      in 5.0 Gy per fraction. Total chemotherapy cycles were 189, and the average
      patient received 4.1 courses. Two cases (4%, 2/46) experienced grade III
      gastrointestinal toxicities, no patients suffered grade IV gastrointestinal
      toxicities. Fifteen cases (33%, 15/46) experienced grade III hematological
      toxicities, and 3(7%, 3/46) experienced grade IV hematological toxicities.Late
      grade III-IV toxicity was seen in 3 cases (7%, 3/46). The 3 year progression-
      free survival rate was 46.2%, and the 3 years overall survival rate was 61.2%.
      CONCLUSION: EF-IMRT and intra-cavitary brachytherapy combined with chemotherapy
      is safe and effective for stageIb1-IVa cervical cancer with positive para-aortic
      lymph nodes.

PMID- 24332134
TI  - [Association of polymorphisms in signal transducer and activator of transcription
      4 gene and the susceptibility to unexplained recurrent spontaneous abortions].
AB  - OBJECTIVE: To investigate the association between the polymorphisms of signal
      transducer and activator of transcription 4 (STAT4) gene and the susceptibility
      to unexplained recurrent spontaneous abortion(URSA). METHODS: PCR-restriction
      fragment length polymorphism (PCR-RFLP) was used to detect genotype 3 loca
      (rs7574865 G/T, rs10181656 C/G and rs16833431 C/T) polymorphism of STAT4 in 246
      URSA cases (URSA group) and 183 normal controls (control group) . RESULTS: (1)The
      frequencies of rs7574865 were genotype G/G of 36.2% (89/246) in URSA group and
      46.4% (85/183) in control group, genotype G/T of 47.2% (116/246) in URSA group
      and 45.4% (83/183) in control group, and genotype T/T of 16.7% (41/246) in URSA
      group and 8.2% (15/183) in control group, which reached statistical difference (P
      < 0.05). The frequencies of rs10181656 were genotype CC of 36.6% (90/246) in URSA
      group and 46.4% (85/183) in control group, genotype C/G of 48.0% (118/246) in
      URSA group and 44.8% (82/183) in control group, and genotype G/G of 15.4%
      (38/246) in URSA group and 8.7% (16/183) in control group, which reached
      statistical difference (P < 0.05). The carriers of rs7574865 T allele and
      rs10181656 G allele increased the risk of URSA (OR = 1.51, 1.44, all P <
      0.05).(2) There was no different distribution in 3 genotypes (C/C, C/T, T/T) and
      2 alleles (C and T) of rs16833431 C/T between URSA patients and normal controls
      (P = 0.43,0.48). (3) Timated haplotype frequency distribution of rs7574865 G/T
      and rs10181656 C/G showed haplotype G-T conferring the susceptibility to URSA (OR
      = 1.49, P < 0.01), but haplotype C-G could provide protection on URSA (OR = 0.68,
      P < 0.01). CONCLUSION: Polymorphisms of STAT4 gene might confer the
      susceptibility to URSA by altering STAT4 function and (or) its expression.

PMID- 24332131
TI  - [Pregnancy outcomes of 103 women with pulmonary arterial hypertension].
AB  - OBJECTIVE: To evaluate the pregnancy outcome of women with pulmonary arterial
      hypertension (PAH). METHODS: The medical records of 103 pregnant women with PAH
      admitted to Beijing Anzhen Hospital from January 2007 to March 2011 were studied
      retrospectively. RESULTS: (1) Degree of PAH and cardiac function. Among the 103
      PAH, 92 cases were patients with congenital heart disease and 13 cases were with
      rheumatic heart disease. They were divided by color doppler ultrasound into mild
      PAH group (34 cases), moderate PAH group (22 cases) and severe PAH group (47
      cases). Per heart function classification, 21 cases (20.4%, 21/103) were class I,
      44 cases (42.7%, 44/103) were class II, 27 cases (26.2%, 27/103) were class III
      and 11 cases (10.7%, 11/103) were class IV. More patients were class III and IV
      cardiac function in the severe PAH group than in the mild and moderate PAH
      groups, with statistically significant difference (P < 0.05). (2) Delivery mode.
      There were 44 term delivery and 23 preterm birth in the 103 PAH patients.Sixty
      three cases (94%, 63/67) received cesarean section and 4 cases had vaginal
      delivery. There were 36 iatrogenic abortion (35.0%, 36/103). The iatrogenic
      abortion rate in the severe PAH group was significantly higher than those in the
      mild and moderate PAH groups (P < 0.05).(3) Perinatal outcomes. The full-term
      delivery rates in the mild and moderate PAH groups [80% (20/25) and 14/17] were
      significantly higher than the severe PAH group (40%, 10/25), respectively (P <
      0.05). And the premature birth rate of the severe PAH group(60%, 15/25) was
      significantly higher than the mild and moderate PAH group [20% (5/25) and 3/17, P
      < 0.05]. There were 4 neonatal asphyxia. The birth weight of mild, moderate and
      severe PAH groups were (3071 +/- 443), (2910 +/- 619) and (2381 +/- 589) g,
      respectively. The birth weight in the severe PAH group was significantly lower
      than the mild and moderate PAH groups (P < 0.05). (4) Mortality. Nine cases
      maternal death happened, with a mortality of 8.7% (9/103). All of them were
      severe pulmonary hypertension patients. CONCLUSIONS: PAH is a serious
      complication during pregnancy.Women with mild PAH and normal cardiac function
      could continue pregnancy to full-term.Women with moderate PAH might continue
      pregnancy to 32 weeks under intensive care, cesarean delivery is preferable.
      Pregnant women with severe PAH should terminate pregnancy because of the high
      mortality.

PMID- 24332132
TI  - [Clinical study of 67 cases of endometriosis coexisting with genital tract
      anomalies].
AB  - OBJECTIVE: To investigate the pathogenesis of endometriosis by studying
      endometriosis coexisting with variable genital tract anomalies and analysis the
      association between obstructive or non-obstructive anomalies with endometriosis.
      METHODS: From January 2000 to April 2010, a total of 67 cases of endometriosis
      coexisting with genital tract anomalies undergoing treatment in Peking Union
      Medical College Hospital were studied retrospectively. RESULTS: According to
      subtypes of concurrent genital tract anomalies, 67 cases were divided into 19
      cases in obstructive group and 48 cases in non-obstructive group.(1) Age and
      symptoms:the mean age were (22 +/- 8) years in obstructive group and (32 +/- 7)
      years in non-obstructive group, which reached statistical difference (P < 0.05).
      The major symptoms were dysmenorrheal or chronic pelvic pain (14/19) and
      amenorrhea (8/19) in obstructive group.However, in non-obstructive group, the
      major symptoms were dysmenorrheal or chronic pelvic pain (31%, 15/48) and
      infertility (35%, 17/48) and abortion (21%, 10/48).(2) Degree and incidence of
      endometriosis:the moderate or severe endometriosis was 11/19 in obstructive group
      and 40% (19/48) in non-obstructive group, which did not show statistical
      difference (P > 0.05). The incidence of peritoneal endometriosis, ovarian
      endometriosis, adenomyosis did not show significant difference between two groups
      (all P > 0.05). The rate of moderate or severe endometriosis coexisting with
      duplex uterus, uterus bicornis and uterus septus did not show significant
      difference in non-obstructive group (P > 0.05). CONCLUSIONS: The severity of
      endometriosis showed no association with obstructive anomalies. The results
      implied that there might be other factors involved in pathogenesis of
      endometriosis.

PMID- 24332126
TI  - Testicular tumor detected within 1 year after orchiopexy in a 2-year-old boy.
AB  - The cause of testicular cancer remains controversial and thought to be
      multifactorial. However, more recent data show that carcinogenic potential of
      altered testicular environment might induce cancer and that early surgical
      correction might decrease the chance of cancer development. We report a case of a
      20-month-old boy who underwent radical orchiectomy because of testicular cancer
      detected 9 months after orchiopexy of undescended testis. 

PMID- 24332133
TI  - [Application of oxytocin antagonists in thaw embryo transfer].
AB  - OBJECTIVE: To study the effects of oxytocin antagonists-atosiban on pregnancy
      outcome after thaw embryo transfer (TET). METHODS: Between Jul. and Dec. 2012, a
      total of 120 women undergoing TET in Reproductive Medical Center, General
      Hospital of Tianjin Medical University were randomly allocated into atosiban and
      control group. They were all transferred 2 or 3 top quality embryos at phase of 7
      8 cells . Patients in atosiban group were administered by intravenous
      administration of atosiban before 30 minutes of embryo transfer with a total
      administered dose of 37.5 mg. In the control group, no special treatment was
      given before embryo transfer. All patients in 2 groups underwent progesterone
      luteal support regularly after embryo transfer, then the clinical rate of
      pregnancy, implantation and early abortion was compared. RESULTS: The clinical
      pregnancy rate per cycle and implantation rate per transfer were 60% (36/60) and
      30.0% (48/160) in the atosiban group, which were higher than 42% (25/60) and
      20.3% (31/153) in the control group (all P < 0.05). Early abortion rate was 6%
      (2/36) in the atosiban group, which was no statistical difference comapring with
      control group [16% (4/25), P > 0.05]. CONCLUSION: It was suggested that atosiban
      treatment before embryo transfer can improve the outcome of pregnancy, and
      increase clinical pregnancy rate and implantation rate after TET.

PMID- 24332135
TI  - [Biological effects of upregulated expression of transfected FOLR1 gene on SKOV3
      cell lines acted by cisplatin].
AB  - OBJECTIVE: To explore biological effects of up-regulated expression of
      transfected FOLR1 gene on SKOV3 cell lines following action by cisplatin (DDP) .
      METHODS: Three groups of cells originated from the same SKOV3 cell line were used
      in this research, including the SKOV3 cell line(blank control), the cell line
      transfected with lentiviral pWPI plasmid(no-load control) and the cell line
      transfected with FOLR1 gene via lentiviral pWPI plasmid(experimental group).
      Next, the mRNA and protein expression of FOLR1 gene in the three groups were
      detected by reverse transcription (RT) -PCR and western blot, respectively.
      Methyl thiazolyl tetrazolium (MTT) assay was used to analysis cells growth curve
      and identify their sensitivity to cisplatin, and their half inhibition
      concentration(IC50) values were calculated. Based on the IC50 value(3.6 ug/ml) in
      the experimental group, different levels of cisplatin concentration (0.5*IC50,
      1*IC50, 2*IC50, respectively) were administered to the three groups of cells, and
      the inhibition rates, apoptosis rates as well as apoptosis proportion of each
      group after 24, 48, 72 hours were further recorded.Finally, the residual
      cisplatin concentrations in the three group cells acted successively by 1*IC50
      cisplatin for 48 hours were measured by high performance liquid chromatography
      (HPLC) . P value less than 0.05 were defined as statistically significant.
      RESULTS: RT-PCR and western blot detection showed that stable mRNA and protein
      expression of the FOLR1 gene in the experimental group while the other two groups
      were not. MTT assay demonstrated that higher cell growth rate, sensitivity to
      cisplatin(IC50 = 3.6 ug/ml) and inhibition rate in the experimental group
      compared with those in the other two groups (P < 0.05) , which showed no
      significance in intergroup comparison(P > 0.05). Flow cytometry showed apoptosis
      rates among three groups increased with higher cisplatin concentrations and
      longer action duration in dosage-time dependent manner (P < 0.05) , and the
      proportion of S phase cells increased with higher cisplatin concentration in
      dosage-dependent manner (P < 0.05) ;for the same concentration and duration, the
      experimental group showed significantly different apoptosis rates and S phase
      cells compared with the other two groups, which demonstrated no significance in
      intergroup comparison (P > 0.05) . After action by cisplatin(3.6 ug/ml) for 48
      hours, HPLC showed significantly higher residual cisplatin concentration (2.60 +/
      0.21) ug/10(6) cell counts in experimental group than those in no-load control
      group (1.49 +/- 0.12) ug/10(6) cell counts and blank control group(1.54 +/- 0.11)
      ug/10(6) cell counts, respectively (P < 0.05) , and the comparison within the
      latter two groups showed no significance (P > 0.05). CONCLUSION: Up-regulated
      expression of the transfected FOLR1 gene in SKOV3 cells may be associated with
      higher sensitivity to cisplatin, residual cisplatin concentration and higher
      proportion of S phase cells, and tended to inhibit cancer cells growth and induce
      apoptosis.

PMID- 24332130
TI  - [Study of the radiotherapy modality for patients with stage IIb-IIIb cervical
      stump cancer].
AB  - OBJECTIVE: To investigate the radiotherapy modality progress of stageIIb-IIIb
      cervical stump cancer. METHODS: The clinical data of 13 patients with stageIIb
      IIIb cervical stump cancer undergoing radiotherapy from January 2000 to April
      2012 was reviewed. Before 2006, 8 patients received conventional external beam
      radiotherapy and brachytherapy.Since 2006, 5 patients received intensity
      modulated radiotherapy (IMRT) and brachytherapy. RESULTS: The median survival was
      12-139 months. The median overall survivals and disease free survivals in the
      conventional radiotherapy (CRT) group were 57 months and 50 months, 3 cases of
      them recurred during 8-19 months and died of tumor progression.While, the median
      overall survivals and disease free survival in the IMRT group both were 21 months
      and nobody recurred. In the CRT group, 7 patients suffered toxicities, including
      5 patients grade I-II acute rectum reaction, 2 patients grade I bladder reaction;
      and 3 had grade I-III, late rectum reaction, 2 patients for grade II bladder late
      reaction.In the IMRT group, toxicities including 1 case grade I acute or late
      rectum reaction, and no bladder reaction. CONCLUSION: In our experience, the
      recommended IMRT and interstitial brachytherapy for the selected patients with
      advanced cervical stump carcinoma may be obtain better tumor dose distribution
      and more sparing of the organ at risk.

PMID- 24332136
TI  - Complete vs culprit-only revascularization for patients with multivessel disease
      undergoing primary percutaneous coronary intervention for ST-segment elevation
      myocardial infarction: a systematic review and meta-analysis.
AB  - BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI) and
      multivessel coronary artery disease who undergo primary percutaneous coronary
      intervention (PCI) are most commonly treated with PCI to the culprit lesion only.
      Whether a strategy of complete revascularization in these patients is superior is
      unknown. We performed a meta-analysis comparing the benefits and risks of routine
      culprit-only PCI vs multivessel PCI in STEMI. METHODS: MEDLINE, EMBASE, ISI Web
      of Science, and The Cochrane Register of Controlled Trials were searched from
      1996 to January 2011. Relevant conference abstracts were searched from January
      2002 to January 2011. Studies included STEMI with multivessel disease receiving
      primary PCI. The primary end point was long-term mortality. Data were combined
      using a fixed-effects model. RESULTS: Of 507 citations, 26 studies (3 randomized,
      23 nonrandomized; 46,324 patients, 7886 multivessel PCI and 38,438 culprit-only
      PCI) were included. There was no significant difference in hospital mortality
      with multivessel PCI vs culprit-only PCI (odds ratio [OR] 1.11, 95% CI 0.98-1.25,
      P = .10 [randomized OR 0.24, 95% CI 0.06-0.91, P = .04; nonrandomized OR 1.12,
      95% CI 1.00-1.27, P = .06]). However, if multivessel PCI during index
      catheterization was performed, hospital mortality was increased (OR 1.35, 95% CI
      1.19-1.54, P < .001). When multivessel PCI was performed as a staged procedure,
      hospital mortality was lower (OR 0.35, 95% CI 0.21-0.59; P < .001; P interaction
      < .001). Reduced long-term mortality (OR 0.74, 95% CI 0.65-0.85, P <
      .001[randomized OR 0.61, 95% CI 0.28-1.33, P = .22; nonrandomized OR 0.75, 95% CI
      0.65-0.86, P < .001]) and repeat PCI (OR 0.65; 95% 0.46-0.90, P = .01[randomized
      OR 0.31, 95% CI 0.17-0.57, P < .001; nonrandomized OR 0.88, 95% CI 0.59-1.31, P =
      .54]) were observed with multivessel PCI. CONCLUSION: Overall, staged multivessel
      PCI improved short- and long-term survival and reduced repeat PCI. Still, large
      randomized trials are required to confirm the benefits of staged multivessel PCI
      in STEMI.

PMID- 24332138
TI  - Rationale and design of REVEAL AF: a prospective study of previously undiagnosed
      atrial fibrillation as documented by an insertable cardiac monitor in high-risk
      patients.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and
      mortality. Sometimes, AF exists but is undiagnosed; yet, its risk for
      consequences still exists. Identifying unrecognized episodes of AF in patients
      without known AF but at high risk for AF is critical for guiding preventative
      therapy decisions. The incidence of AF in high-risk patients, understanding how
      physicians manage these patients once AF has been detected, and knowing which
      patient characteristics are most predictive of developing AF are all unknown.
      METHODS: REVEAL AF is a prospective, single-arm, open-label, multicenter,
      interventional study to evaluate the incidence of AF >=6 minutes in patients
      without known AF but who may be at high risk for AF based on symptoms and/or
      demographic criteria. The Reveal Insertable Cardiac Monitor will be implanted in
      400 patients, and these patients will be followed up for a minimum of 18 months
      to monitor for the detection of AF, up to a maximum of 30 months or until the
      last patient has completed their 18-month follow-up visit. CONCLUSIONS: REVEAL AF
      will determine the incidence rate of AF lasting >=6 minutes in patients who are
      at high risk for having AF. Secondary outcomes include observations regarding
      physician actions in response to detected AF and determination of risk markers
      for AF development.

PMID- 24332141
TI  - Comparative effectiveness of upstream glycoprotein IIb/IIIa inhibitors in
      patients with moderate- and high-risk acute coronary syndromes: an Acute
      Catheterization and Urgent Intervention Triage Strategy (ACUITY) substudy.
AB  - BACKGROUND: Tirofiban and eptifibatide are both small-molecule, competitive
      glycoprotein IIb/IIIa receptor inhibitors (GPIs) that are guideline-supported for
      upstream therapy in acute coronary syndromes (ACS). This study sought to compare
      the efficacy and safety of tirofiban and eptifibatide in patients with ACS.
      METHODS: Within the ACUITY trial, 4,323 patients with moderate- and high-risk ACS
      received upstream, adjunctive GPI (tirofiban or eptifibatide) in addition to an
      antithrombin. Primary outcomes included 30-day rates of composite major adverse
      cardiac events (MACE), major bleeding (not related to coronary artery bypass
      grafting), and composite net adverse clinical events (NACE). The outcomes were
      compared based on the upstream GPI administered. RESULTS: There were significant
      differences in the baseline characteristics of patients treated with tirofiban vs
      eptifibatide, particularly related to country/region. In unadjusted analyses,
      treatment with upstream tirofiban vs eptifibatide was associated with similar
      rates of major bleeding (5.8% vs 6.5%, P = .39) and nonsignificantly lower rates
      of MACE (6.1% vs 7.6%, P = .06) and NACE (10.6% vs 12.6%, P = .06). After
      propensity-based multivariable adjustment, there were no significant differences
      between tirofiban and eptifibatide with respect to 30-day major bleeding, MACE,
      or NACE. CONCLUSIONS: Among more than 4,000 patients with moderate- and high-risk
      ACS treated with upstream GPI as part of an early invasive management strategy,
      the use of tirofiban and eptifibatide resulted in similar clinical outcomes.
      These data suggest equivalence of these 2 agents for upstream use, while
      highlighting some of the difficulties of nonrandomized comparative effectiveness
      analyses, specifically the difficulty in addressing geographic differences in the
      use of nonrandomized treatments.

PMID- 24332122
TI  - The expression and evaluation of androgen receptor in human renal cell carcinoma.
AB  - OBJECTIVE: To investigate the expression of androgen receptor (AR) with clinical
      and pathologic features in patients with renal cell carcinoma (RCC) and to
      explore the function of AR using human RCC cells. MATERIALS AND METHODS: The
      expression of AR was detected by immunohistochemistry in 44 adjacent normal
      kidney tissues of 120 RCC patients and also in 16 metastatic RCC patients with
      their respective primary and metastatic tissue samples. The expression of AR was
      examined by western blot in commonly used human RCC cell lines and normal kidney
      epithelial cells, and the luciferase assay was performed in those AR-positive RCC
      cells. RESULTS: The expression rate of AR was higher in adjacent normal kidney
      (90.9%) than in RCC tissues (30.0%, P <.001), and it was negatively associated
      with pT stage and Fuhrman's grade. Specifically, there were 40.7% AR-positive
      cases in pT1 compared with 8.0% in pT3 (P = .013), and 50.0% of grade I cases
      were found to be AR positive compared with 12.9% in grade III (P = .008). AR
      expression was slightly higher in primary RCC tissues (12.5%) than their
      respective metastases (0%, P = .484). AR strongly expressed in CAKI-2 and OSRC-2
      cells with little transactivation, which might indicate that AR in those 2 RCC
      cells has little function. CONCLUSION: Our results suggest that any attempt to
      investigate the roles of AR in RCC progression might need to combine the
      detection of AR expression in tissue samples with examining its function to make
      a correct correlation between AR and RCC progression.

PMID- 24332137
TI  - Regional systems of care demonstration project: Mission: Lifeline STEMI Systems
      Accelerator: design and methodology.
AB  - ST-segment elevation myocardial infarction (STEMI) systems of care have been
      associated with significant improvement in use and timeliness of reperfusion.
      Consequently, national guidelines recommend that each community should develop a
      regional STEMI care system. However, significant barriers continue to impede
      widespread establishment of regional STEMI care systems in the United States. We
      designed the Regional Systems of Care Demonstration Project: Mission: Lifeline
      STEMI Systems Accelerator, a national educational outcome research study in
      collaboration with the American Heart Association, to comprehensively accelerate
      the implementation of STEMI care systems in 17 major metropolitan regions
      encompassing >1,500 emergency medical service agencies and 450 hospitals across
      the United States. The goals of the program are to identify regional gaps,
      barriers, and inefficiencies in STEMI care and to devise strategies to implement
      proven recommendations to enhance the quality and consistency of care. The study
      interventions, facilitated by national faculty with expertise in regional STEMI
      system organization in partnership with American Heart Association
      representatives, draw upon specific resources with proven past effectiveness in
      augmenting regional organization. These include bringing together leading
      regional health care providers and institutions to establish common commitment to
      STEMI care improvement, developing consensus-based standardized protocols in
      accordance with national professional guidelines to address local needs, and
      collecting and regularly reviewing regional data to identify areas for
      improvement. Interventions focus on each component of the reperfusion process:
      the emergency medical service, the emergency department, the catheterization
      laboratory, and inter-hospital transfer. The impact of regionalization of STEMI
      care on clinical outcomes will be evaluated. 

PMID- 24332140
TI  - Trends in outcomes among older patients with non-ST-segment elevation myocardial
      infarction.
AB  - OBJECTIVES: The objective of this study is to assess trends in evidence-based
      therapy use and short- and long-term mortality over time among older patients
      with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: With
      the prevalence of national quality improvement efforts, the use of evidence-based
      therapies has improved over time among patients with NSTEMI, yet it is unclear
      whether these improvements have been associated with significant change in short-
      and long-term mortality for older patients. METHODS: We linked detailed clinical
      data for 28,603 NSTEMI patients aged >=65 years at 171 hospitals in the Can Rapid
      Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with
      Early Implementation of the American College of Cardiology/American Heart
      Association Guidelines Registry with longitudinal Centers for Medicare & Medicaid
      claims data and compared trends in annual unadjusted and risk-adjusted inhospital
      and long-term mortality from 2003 to 2006. RESULTS: The median age of our NSTEMI
      study population was 77 years, 48% were female, and 87% were white. Overall,
      inhospital and 1-year mortality rates were 6.0% and 24.5%, respectively. When
      compared with patients treated in 2003, NSTEMI patients treated in 2006 were more
      likely to receive guideline-recommended inhospital medications and early invasive
      treatment. Inhospital mortality decreased significantly over the study period
      (5.5% vs 7.2% [adjusted odds ratio 0.82, 95% CI 0.67-1.00, P = .045] for 2006 vs
      2003), but there was no significant change in 1-year mortality from the index
      admission (24.0% vs 26.0% [adjusted hazard ratio 0.99, 95% CI 0.90-1.08] for 2006
      vs 2003). CONCLUSIONS: Between 2003 and 2006, there was a significant reduction
      in inhospital mortality that corresponded to an increase in the use of evidence
      based NSTEMI care. Nevertheless, long-term outcomes have not changed over time,
      suggesting a need for improved care transition and longitudinal secondary
      prevention.

PMID- 24332144
TI  - In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute
      coronary syndrome undergoing percutaneous coronary intervention: prevalence,
      predictors and short-term outcome.
AB  - BACKGROUND: P2Y12 inhibitor switching has appeared in clinical practice as a
      consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for
      use in patients with acute coronary syndrome (ACS) undergoing percutaneous
      coronary intervention (PCI). METHODS: In the context of the GReek AntiPlatelet
      REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term
      outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing
      PCI. RESULTS: Switching occurred in 636 (35.5%) patients of which in the form of
      clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel
      and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively.
      Presentation to non PCI-capable hospital, bivalirudin use, age >=75 years
      (inverse predictor), and regional trends emerged as predictive factors of
      switching to a novel agent. At combined in-hospital and one-month follow-up,
      propensity matched pairs analysis showed no differences in major adverse
      cardiovascular (MACE) or bleeding events between switching from clopidogrel to a
      novel agent vs novel agent constant administration. More Bleeding Academic
      Research Consortium type 1, type 2 and any type events and fewer MACE were seen
      when switching from clopidogrel to a novel agent vs only clopidogrel
      administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P <
      .001, P = .03, P < .001 and P = .03 respectively). CONCLUSIONS: In a real-life
      experience with contemporary antiplatelet treatment in ACS patients undergoing
      PCI, in-hospital switching represents common clinical practice. Clinical factors
      and regional practice differences seem to affect this strategy's choice, while
      switching to a novel agent may be associated with higher risk of bleeding.

PMID- 24332147
TI  - Using an online, personalized program reduces cardiovascular risk factor profiles
      in a motivated, adherent population of participants.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity,
      mortality, and cost in Western society. Employer-sponsored work health programs
      (WHPs) and Web-based portals for monitoring and providing guidance based on
      participants' health risk assessments are emerging, yet online technologies to
      improve CVD health in the workplace are relatively unproven. We hypothesized that
      an online WHP, comprehensively addressing multiple facets of CVD, can be
      successfully implemented and improve the health of participants. METHODS: A
      cohort of employees in Tennessee (n = 1,602) was subjected to a health risk
      assessment at baseline. Those who did not meet all 5 healthy benchmarks (n = 836)
      body mass index, blood pressure, glucose, total cholesterol, and smoking status
      were prospectively assigned to a Web-based personal health assistant and had
      repeat measurements taken at 90 days. RESULTS: Of those who both completed the
      personal health assistant program and underwent baseline plus 90-day assessments
      (508/836, 61%), 75% were female, mean age was 46.5 +/- 11.1 years, and the mean
      number of risk factors at baseline was 1.1 +/- 0.9 with a mean 10-year Framingham
      Risk Score of 2.9%. This cohort demonstrated a significant reduction in total
      cholesterol (P < .0001), low-density lipoprotein cholesterol (P < .0001),
      triglycerides (P < .0001), systolic blood pressure (P = .009), glucose (P =
      .004), weight (P = .001), and body mass index (P = .001). Most of the
      participants improved at least 1 risk factor. Framingham Risk 10-year
      cardiovascular risk percentages were significantly reduced (P = .003).
      CONCLUSIONS: This study in a prospective cohort of community-dwelling employees
      suggests that an online WHP can provide a viable means to improve surrogates of
      CVD risk factors.

PMID- 24332142
TI  - Untangling the relationship between medication adherence and post-myocardial
      infarction outcomes: medication adherence and clinical outcomes.
AB  - BACKGROUND: Patients who adhere to medications experience better outcomes than
      their nonadherent counterparts. However, these observations may be confounded by
      patient behaviors. The level of adherence necessary for patients to derive
      benefit and whether adherence to all agents is important for diseases that
      require multiple drugs remain unclear. This study quantifies the relationship
      between medication adherence and post-myocardial infarction (MI) adverse coronary
      events. METHODS: This is a secondary analysis of the randomized MI FREEE trial.
      Patients who received full prescription coverage were classified as adherent
      (proportion of days covered >=80%) or not based upon achieved adherence in the 6
      months after randomization. First major vascular event or revascularization rates
      were compared using multivariable Cox models adjusting for comorbidity and health
      seeking behavior. RESULTS: Compared with patients randomized to usual care, full
      coverage patients adherent to statin, beta-blocker, or angiotensin-converting
      enzyme inhibitor/angiotensin receptor blocker were significantly less likely to
      experience the study's primary outcome (hazard ratio [HR] range 0.64-0.81). In
      contrast, nonadherent patients derived no benefit (HR range 0.98-1.04, P <= .01
      for the difference in HRs between adherent and nonadherent patients). Partially
      adherent patients had no reduction in clinical outcomes for any of the drugs
      evaluated, although their achieved adherence was higher than that among controls.
      CONCLUSION: Achieving high levels of adherence to each and all guideline
      recommended post-MI secondary prevention medication is associated with improved
      event-free survival. Lower levels of adherence appear less protective.

PMID- 24332143
TI  - Pancoronary plaque vulnerability in patients with acute coronary syndrome and
      ruptured culprit plaque: a 3-vessel optical coherence tomography study.
AB  - BACKGROUND: Recent studies described different clinical and underlying plaque
      characteristics between patients with and without plaque rupture presenting with
      acute coronary syndrome (ACS). In light of the systemic nature of
      atherosclerosis, we hypothesized that nonculprit plaques might also express
      different morphological features in these 2 groups of patients. METHODS: Thirty
      eight patients with ACS who underwent 3-vessel optical coherence tomography
      imaging were identified from the Massachusetts General Hospital Optical Coherence
      Tomography Registry. Based on culprit plaque morphology, the study population was
      divided into 2 groups: patients with plaque rupture at the culprit lesion (group
      1) and patients with nonruptured plaque at the culprit lesion (group 2).
      Prevalence and features of nonculprit plaques were compared between the 2 groups.
      RESULTS: A total of 118 nonculprit plaques were analyzed. Patients in group 1 (n
      = 17) had nonculprit plaques with higher prevalence of thin-cap fibroatheroma
      (52.9% vs 19.0%, P = .029) and disruption (35.3% vs 4.8%, P = .016) compared with
      patients in group 2 (n = 21). Nonculprit plaques in group 1 showed wider maximum
      lipid arc (198.9 degrees  +/- 41.7 degrees  vs 170.2 degrees  +/- 41.9 degrees ,
      P = .003), greater lipid length (7.8 +/- 4.4 mm vs 5.1 +/- 2.4 mm, P = .003),
      higher lipid index (1196.9 +/- 700.5 vs 747.7 +/- 377.3, P = .001), and thinner
      fibrous cap (107.0 +/- 56.5 MUm vs 137.3 +/- 69.8 MUm, P = .035) compared with
      those in group 2. CONCLUSIONS: The present study showed distinctive features of
      nonculprit plaques between patients with ACS caused by plaque rupture and
      patients with ACS caused by nonruptured plaques. Patients with plaque rupture had
      increased pancoronary vulnerability in nonculprit plaques, suggesting that a more
      aggressive treatment paradigm aiming at the stabilization of vulnerable plaques
      may offer additional benefit to these patients.

PMID- 24332145
TI  - Prognostic value of stress imaging after revascularization: a systematic review
      of stress echocardiography and stress nuclear imaging.
AB  - BACKGROUND: Risk assessment may be important in patients being considered for
      repeat revascularization after prior coronary intervention or surgery. We sought
      the prognostic value of radionuclide stress myocardial perfusion imaging or
      echocardiography among patients with previous revascularization. METHODS: Studies
      on the outcomes of stress imaging tests after revascularization were selected
      from an electronic search if they reported the odds or hazard ratio (HR) of an
      abnormal stress test in the prediction of mortality (cardiac or total), hard
      cardiac events (cardiac death and myocardial infarction [MI]), total hard events
      (total mortality and MI]), or overall events (cardiac death, MI, and repeat
      revascularization). RESULTS: In 29 studies (12,874 patients, 63 +/- 3 years, 80%
      men), an abnormal test result was associated with hard cardiac events (HR 1.2,
      95% CI 1.1-1.3), cardiac mortality (HR 5.8, 95% CI 0.8-10.8), total mortality (HR
      2.2, 95% CI 1.3-3.1), total hard events(HR 2.4, 95% CI 1.4-3.3), and overall
      events (HR 1.2, 95% CI 1.1-1.3). The nature of the end point was not associated
      with differences in the prediction of events, but the type of revascularization
      showed a significant association with outcome, with percutaneous intervention
      portending a worse outcome. Age and the timing of the stress imaging
      postrevascularization were inversely associated with survival. Gender, length of
      follow-up after testing, symptom status, past infarction, and risk factor status
      did not explain interstudy heterogeneity. CONCLUSIONS: In patients with previous
      revascularization, abnormal results at stress echocardiography or radionuclide
      myocardial perfusion imaging are predictive of subsequent events, with age, type
      of revascularization, and the timing of the stress imaging after
      revascularization being important sources of heterogeneity between studies.

PMID- 24332153
TI  - Reply to Jolobe.

PMID- 24332152
TI  - Also beware of inaccuracies in the estimation of renal function.

PMID- 24332155
TI  - A computer vision framework for finger-tapping evaluation in Parkinson's disease.
AB  - OBJECTIVES: The rapid finger-tapping test (RFT) is an important method for
      clinical evaluation of movement disorders, including Parkinson's disease (PD). In
      clinical practice, the naked-eye evaluation of RFT results in a coarse judgment
      of symptom scores. We introduce a novel computer-vision (CV) method for
      quantification of tapping symptoms through motion analysis of index-fingers. The
      method is unique as it utilizes facial features to calibrate tapping amplitude
      for normalization of distance variation between the camera and subject. METHODS:
      The study involved 387 video footages of RFT recorded from 13 patients diagnosed
      with advanced PD. Tapping performance in these videos was rated by two clinicians
      between the symptom severity levels ('0: normal' to '3: severe') using the
      unified Parkinson's disease rating scale motor examination of finger-tapping
      (UPDRS-FT). Another set of recordings in this study consisted of 84 videos of RFT
      recorded from 6 healthy controls. These videos were processed by a CV algorithm
      that tracks the index-finger motion between the video-frames to produce a tapping
      time-series. Different features were computed from this time series to estimate
      speed, amplitude, rhythm and fatigue in tapping. The features were trained in a
      support vector machine (1) to categorize the patient group between UPDRS-FT
      symptom severity levels, and (2) to discriminate between PD patients and healthy
      controls. RESULTS: A new representative feature of tapping rhythm, 'cross
      correlation between the normalized peaks' showed strong Guttman correlation (MU2=
      0.80) with the clinical ratings. The classification of tapping features using the
      support vector machine classifier and 10-fold cross validation categorized the
      patient samples between UPDRS-FT levels with an accuracy of 88%. The same
      classification scheme discriminated between RFT samples of healthy controls and
      PD patients with an accuracy of 95%. CONCLUSION: The work supports the
      feasibility of the approach, which is presumed suitable for PD monitoring in the
      home environment. The system offers advantages over other technologies (e.g.
      magnetic sensors, accelerometers, etc.) previously developed for objective
      assessment of tapping symptoms.

PMID- 24332139
TI  - Influence of cardiovascular absolute risk assessment on prescribing of
      antihypertensive and lipid-lowering medications: a cluster randomized controlled
      trial.
AB  - BACKGROUND: Guidelines for management of hypertension and lipids recommend using
      cardiovascular absolute risk (CVAR) to manage patients. This randomized
      controlled trial investigated the impact of CVAR assessment in family practice on
      management of cardiovascular risk, including prescription of antihypertensive and
      lipid-lowering medication. METHODS: A cluster randomized controlled trial was
      conducted from 2008 to 2010 in Sydney, Australia. Family practices were
      randomized, and patients aged 45 to 69 years were invited to participate.
      Intervention family physicians (FP) were trained in use of CVAR, provided with an
      electronic CVAR calculator, and assessed their patients' absolute risk in a
      dedicated consultation. Control practice patients received a general health
      check. Primary outcome analyzed was the proportion of patients in each group on
      antihypertensive and/or lipid-lowering medication at 12 months. Multilevel
      logistic regression was performed to explore variables influencing changes in
      pharmacologic therapy. RESULTS: The study recruited 36 FPs from 34 practices and
      1,074 patients, of which 906 (84.4%) completed 12-month follow-up. At 12 months,
      there was no significant difference between the intervention and control groups
      in proportion of patients on antihypertensives (31.2% vs 34.3%, P = .31), but
      control group patients were more likely to be on lipid-lowering medications
      (30.2% vs 22.7%, P = .01). After multilevel analysis, this difference was not
      present. Intensification or reduction of pharmacologic therapy was associated
      with meeting treatment targets for blood pressure and lipids but not with the
      CVAR or intervention group. CONCLUSIONS: Single-risk factor management remains a
      strong influence on FP prescribing practices. Shifting to an approach based on
      CVAR will require more intensive intervention.

PMID- 24332150
TI  - Gene-environment interaction between SCN5A-1103Y and hypokalemia influences QT
      interval prolongation in African Americans: the Jackson Heart Study.
AB  - BACKGROUND: African-American ancestry, hypokalemia, and QT interval prolongation
      on the electrocardiogram are all risk factors for sudden cardiac death (SCD), but
      their interactions remain to be characterized. SCN5A-1103Y is a common missense
      variant, of African ancestry, of the cardiac sodium channel gene. SCN5A-1103Y is
      known to interact with QT-prolonging factors to promote ventricular arrhythmias
      in persons at high risk for SCD, but its clinical impact in the general African
      American population has not been established. METHODS: We genotyped SCN5A-S1103Y
      in 4,476 participants of the Jackson Heart Study, a population-based cohort of
      African Americans. We investigated the effect of SCN5A-1103Y, including
      interaction with hypokalemia, on QT interval prolongation, a widely-used
      indicator of prolonged myocardial repolarization and predisposition to SCD. We
      then evaluated the two sub-components of the QT interval: QRS duration and JT
      interval. RESULTS: The carrier frequency for SCN5A-1103Y was 15.4%. SCN5A-1103Y
      was associated with QT interval prolongation (2.7 milliseconds; P < .001) and
      potentiated the effect of hypokalemia on QT interval prolongation (14.6
      milliseconds; P = .02). SCN5A-1103Y had opposing effects on the two sub
      components of the QT interval, with shortening of QRS duration (-1.5
      milliseconds; P = .001) and prolongation of the JT interval (3.4 milliseconds; P
      < .001). Hypokalemia was associated with diuretic use (78%; P < .001).
      CONCLUSIONS: SCN5A-1103Y potentiates the effect of hypokalemia on prolonging
      myocardial repolarization in the general African-American population. These
      findings have clinical implications for modification of QT prolonging factors,
      such as hypokalemia, in the 15% of African Americans who are carriers of SCN5A
      1103Y.

PMID- 24332157
TI  - Sentinel lymph node biopsy versus elective neck dissection in patients with cT1
      2N0 oral tongue squamous cell carcinoma.
AB  - OBJECTIVE: This study aimed to compare the value of sentinel lymph node biopsy
      (SLNB) with that of elective neck dissection (END) for the prediction of cervical
      lymph node metastasis in patients with clinically diagnosed T1-2N0 (cT1-2N0) oral
      tongue squamous cell carcinoma (OTSCC), and it aimed to examine the prognostic
      value of individualized treatment in sentinel lymph node (SLN)-negative patients.
      STUDY DESIGN: The study entailed a retrospective review of 82 patients with cT1
      2N0 OTSCC. Thirty patients underwent SLNB, and 52 patients underwent END.
      RESULTS: There was a significant difference between the SLNB and END groups in
      the incidence of occult cervical lymph node metastasis in initial specimens (30%
      vs 11.5%; P = .037). However, there were no significant differences between the
      groups for 10-year overall and cervical recurrence-free survival rates and 10
      year overall survival rate. CONCLUSIONS: SLNB is superior to END for the
      prediction of cervical lymph node metastasis in patients with cT1-2N0 OTSCC. Neck
      dissection may be reduced for SLN-negative patients, owing to the comparable
      prognosis of SLNB.

PMID- 24332151
TI  - Relation of hypothyroidism and incident atrial fibrillation (from the Framingham
      Heart Study).
AB  - BACKGROUND: Hyperthyroidism has a well-described association with atrial
      fibrillation (AF). However, the relation of hypothyroidism to AF has had limited
      investigation. Hypothyroidism is associated with cardiovascular risk factors,
      subclinical cardiovascular disease, and overt cardiovascular disease, all of
      which predispose to AF. We investigated 10-year incidence of AF in a community
      dwelling cohort. METHODS: Among 6,653 Framingham heart Study participants, 5,069
      participants, 52% female, with mean age of 57 +/- 12 years, were eligible after
      excluding those with missing thyroid-stimulating hormone (TSH), TSH <0.45 MUU/L
      (hyperthyroid), TSH >19.9 MUU/L, or prevalent AF. Thyroid-stimulating hormone was
      categorized by range (>=0.45 to <4.5, 4.5 to <10.0, 10.0 to <=19.9 MUU/L) and by
      quartiles. We examined the associations between TSH and 10-year risk of AF using
      multivariable-adjusted Cox proportional hazards analysis. RESULTS: Over 10-year
      follow-up, we observed 277 cases of incident AF. A 1-SD increase in TSH was not
      associated with increased risk of AF (hazard ratio 1.01, 95% CI 0.90-1.14, P =
      .83). In categorical analysis, using TSH >=0.45 to <4.5 MUU/L as the referent
      (equivalent to euthyroid state), we found no significant association between
      hypothyroidism and 10-year AF risk. Comparing the highest (2.6 < TSH < 19.9
      MUU/L) to lowest (0.45 < TSH < 1.3 MUU/L) quartiles of TSH further did not
      identify a significant association between TSH levels and 10-year risk of AF.
      CONCLUSIONS: In conclusion, we did not identify a significant association between
      hypothyroidism and 10-year risk of incident AF in a community-based study.

PMID- 24332161
TI  - Limb reconstruction after traumatic bone loss.
AB  - A variety of options exist to reconstruct limbs following traumatic bone loss.
      The management of these injuries is challenging and often requires prolonged and
      potentially painful treatment. The Ilizarov technique of bone transport using
      circular external fixators is widely used for limb reconstruction of large bone
      defects. Other techniques include vascularised fibular grafting, the use of
      induced pseudosynovial membranes combined with cancellous autologous bone grafts
      and the use of autologous, allogeneic or synthetic bone grafts on their own for
      smaller defects. Future directions include further research on bone tissue
      engineering using stem cell therapy and growth factors such as bone morphogenetic
      proteins. The purpose of this Continuing Medical Education article is to describe
      the key limb reconstructive techniques that may be employed to treat traumatic
      bone loss. In particular, this article is intended to serve as a revision tool
      for those preparing for postgraduate examinations.

PMID- 24332158
TI  - Peripheral odontogenic keratocyst associated with nevoid basal cell carcinoma
      syndrome: a case report.
AB  - OBJECTIVE: Peripheral odontogenic keratocyst (POKC) is a rare gingival cyst
      showing histologic features identical to those of keratocystic odontogenic tumor.
      A rare case of POKC associated with nevoid basal cell carcinoma syndrome (NBCCS)
      is presented. STUDY DESIGN: A 24-year-old woman with NBCCS presented with a
      pigmented papule, 3 mm in size, involving the lingual gingiva of the right canine
      area of the mandible. Based on a clinical diagnosis of benign pigmentation, an
      excisional biopsy was performed, and a histopathologic diagnosis of POKC was
      rendered. RESULTS: The lining cells were positive for the proteins GLI2, BCL2,
      keratin 8, keratin 17, and mTOR. TP53 and Ber-EP4 were also weakly positive. Gene
      mutational analysis on a buccal swab sample revealed 2 missense mutations in the
      PTCH1 gene. CONCLUSIONS: This case is a distinctive example of a genuine soft
      tissue counterpart of keratocystic odontogenic tumor, in which an aberrant PTCH1
      GLI pathway played a considerable role in the pathogenesis.

PMID- 24332160
TI  - Social influences of health literacy and patient empowerment.

PMID- 24332163
TI  - Preliminary evaluation of different biomaterials for defect healing in an
      experimental osteoporotic rat model with dynamic PET-CT (dPET-CT) using F-18
      sodium fluoride (NaF).
AB  - The aim of the current study was to measure and compare the effect of calcium
      phosphate cement (CPC) and CPC enriched with strontium (SrCPC) for the healing of
      osteoporotic bone defects in the rat femur using (18)F-Sodium Fluoride dPET-CT.
      METHODS: Osteoporosis was induced by ovariectomy and a calcium restricted diet.
      After three months, rats were operated to create a 4 mm defect in the distal
      metaphyseal femur with internal fixation. 7 Rats have been treated either with
      CPC (Group 2) or with SrCPC (Group 3) for bone replacement and defect healing.
      Furthermore, a control group of 7 rats without any biomaterial (Group 1) was used
      for reference. 18 weeks after osteoporosis induction and 6 weeks following
      femoral surgery, dPET-CT studies scan were performed with (18)F-Sodium Fluoride.
      SUVs and a 2-tissue compartmental learning-machine model (K1-k4, VB, influx) were
      used for quantitative analysis. RESULTS: VB, reflecting the fractional blood
      volume and k3, reflecting the formation of fluoroapatite were the most sensitive
      parameters for the characterisation of healing process and revealed the best
      differentiation for the control group and the CPC group (Group 2) as well as for
      the CPC with strontium carbonate group (Group 3) (p<0.05). VB was decreased by
      the order of Group 1, Group 2 and Group 3, while k3 was increased by the same
      order. Therefore, the data direct to a decreased fractional blood volume and
      increased fixation of fluoride in rats with these biomaterials. CONCLUSION: We
      found PET scanning using (18)F-Sodium Fluoride to be a sensitive and useful
      method for evaluation of bone healing after replacement with CPC or SrCPC.

PMID- 24332162
TI  - Ultrasounds for prehospital recognition of tension pneumothorax.

PMID- 24332146
TI  - Incremental prognostic information from kidney function in patients with new
      onset coronary heart disease.
AB  - BACKGROUND: Prognostic factors are usually evaluated by their statistical
      significance rather than by their clinical utility. Risk reclassification
      measures the extent to which a novel marker adds useful information to a
      prognostic model. The extent to which estimated glomerular filtration rate (eGFR)
      adds information about prognosis among patients with coronary heart disease is
      uncertain. METHODS: We studied patients in an integrated health care delivery
      system with newly diagnosed coronary heart disease. We developed a model of the
      risk of death over 2 years of follow-up and then added eGFR to the model and
      measured changes in C-index, net reclassification improvement, and integrated
      discrimination improvement. RESULTS: Almost half of the 31,533 study patients had
      reduced eGFR (<60 mL/min per 1.73 m(2)). Mortality was significantly higher among
      patients who had lower levels of eGFR, even after adjustment for baseline
      characteristics (P < .0001). The addition of eGFR to the prognostic model
      increased the C-index from 0.837 to 0.843, the net reclassification improvement
      by 3.2% (P < .0001), and integrated discrimination improvement by 1.3% (P =
      .007). CONCLUSION: Estimated glomerular filtration rate is an informative
      prognostic factor among patients with incident coronary heart disease,
      independent of other clinical characteristics.

PMID- 24332149
TI  - Relation between soluble ST2, growth differentiation factor-15, and high
      sensitivity troponin I and incident atrial fibrillation.
AB  - BACKGROUND: We investigated whether circulating concentrations of soluble ST2,
      growth differentiation factor-15 (GDF-15), and high-sensitivity troponin I
      (hsTnI) are associated with incident atrial fibrillation (AF) and whether these
      biomarkers improve current risk prediction models including AF risk factors, B
      type natriuretic peptide (BNP), and C-reactive protein (CRP). METHODS: We studied
      the relation between soluble ST2, GDF-15, and hsTnI and development of AF in
      Framingham Heart Study participants without prevalent AF. We used Cox
      proportional hazard regression analysis to examine the relation of incident AF
      during a 10-year follow-up period with each biomarker. We adjusted for standard
      AF clinical risk factors, BNP, and CRP. RESULTS: The mean age of the 3,217
      participants was 59 +/- 10 years, and 54% were women. During a 10-year follow-up,
      242 participants developed AF. In age- and sex-adjusted models, GDF-15 and hsTnI
      were associated with risk of incident AF; however, after including the AF risk
      factors and BNP and CRP, only hsTnI was significantly associated with AF (hazard
      ratio per 1 SD of loge hsTnI, 1.12, 95% CI 1.00-1.26, P = .045). The c statistic
      of the base model including AF risk factors, BNP, and CRP was 0.803 (95% CI 0.777
      0.830) and did not improve by adding individual or all 3 biomarkers. None of the
      discrimination and reclassification statistics were significant compared with the
      base model. CONCLUSION: In a community-based cohort, circulating hsTnI
      concentrations were associated with incident AF. None of the novel biomarkers
      evaluated improved AF risk discrimination or reclassification beyond standard
      clinical AF risk factors and biomarkers.

PMID- 24332148
TI  - Genetic variation in the beta1-adrenergic receptor is associated with the risk of
      atrial fibrillation after cardiac surgery.
AB  - BACKGROUND: Postoperative atrial fibrillation (PoAF) after cardiac surgery is
      common and associated with increased morbidity and mortality. Increased
      sympathetic activation after surgery contributes to PoAF, and beta-blockers are
      the first-line recommendation for its prevention. We examined the hypothesis that
      common functional genetic variants in the beta1-adrenoreceptor, the mediator of
      cardiac sympathetic activation and drug target of beta-blockers, are associated
      with the risk for PoAF and with the protective effect of beta-blockers. METHODS:
      In a prospective cohort study, we studied 947 adult European Americans who
      underwent cardiac surgery at Vanderbilt University between 1999 and 2005. We
      genotyped 2 variants in the beta1-adrenoreceptor, rs1801253 (Arg389Gly) and
      rs1801252 (Ser49Gly), and used logistic regression to examine the association
      between genotypes and PoAF occurring within 14 days after surgery, before and
      after adjustment for demographic and clinical covariates. RESULTS: Postoperative
      atrial fibrillation occurred in 239 patients (25.2%) and was associated with
      rs1801253 genotype (adjusted P = .008), with Gly389Gly having an odds ratio of
      2.63 (95% CI 1.42-4.89) for PoAF compared to the common Arg389Arg (P = .002). In
      a predefined subgroup analysis, this association appeared to be stronger among
      patients without beta-blocker prophylaxis (adjusted odds ratio 7.00, 95% CI 1.82
      26.96, P = .005) compared to patients with beta-blocker prophylaxis, among whom
      the association between rs1801253 genotype and PoAF was not statistically
      significant (adjusted P = .11). CONCLUSION: The Gly389 variant in the beta1
      adrenoreceptor is associated with PoAF, and this association appears to be
      modulated by beta-blocker therapy. Future studies of the association of other
      adrenergic pathway genes with PoAF will be of interest.

PMID- 24332164
TI  - MicroRNA-155 modulates Th1 and Th17 cell differentiation and is associated with
      multiple sclerosis and experimental autoimmune encephalomyelitis.
AB  - Mammalian noncoding microRNAs (miRNAs) are suggested to be involved in immune
      system function. We found that miR-155 expression was highly correlated with
      disease severity in patients with multiple sclerosis and mice with experimental
      autoimmune encephalomyelitis (EAE). Knockdown of miR-155 resulted in low Th1 and
      Th17 cells and mild EAE, and its overexpression led to more Th1 and Th17 cells
      and severe EAE. MiR-155 promoted the development of inflammatory Th17/Th1 cell
      subsets. These findings demonstrate that miR-155 confers susceptibility to EAE by
      affecting inflammatory T cell responses and can be a new target for therapy of
      multiple sclerosis. 

PMID- 24332156
TI  - Automatic detection of solitary lung nodules using quality threshold clustering,
      genetic algorithm and diversity index.
AB  - OBJECTIVE: The present work has the objective of developing an automatic
      methodology for the detection of lung nodules. METHODOLOGY: The proposed
      methodology is based on image processing and pattern recognition techniques and
      can be summarized in three stages. In the first stage, the extraction and
      reconstruction of the pulmonary parenchyma is carried out and then enhanced to
      highlight its structures. In the second stage, nodule candidates are segmented.
      Finally, in the third stage, shape and texture features are extracted, selected
      and then classified using a support vector machine. RESULTS: In the testing
      stage, with 140 new exams from the Lung Image Database Consortium image
      collection, 80% of which are for training and 20% are for testing, good results
      were achieved, as indicated by a sensitivity of 85.91%, a specificity of 97.70%
      and an accuracy of 97.55%, with a false positive rate of 1.82 per exam and 0.008
      per slice and an area under the free response operating characteristic of 0.8062.
      CONCLUSION: Lung cancer presents the highest mortality rate in addition to one of
      the smallest survival rates after diagnosis. An early diagnosis considerably
      increases the survival chance of patients. The methodology proposed herein
      contributes to this diagnosis by being a useful tool for specialists who are
      attempting to detect nodules.

PMID- 24332168
TI  - Microstructure assessment of the thalamus in Wilson's disease using diffusion
      tensor imaging.
AB  - AIM: To assess diffusion changes of the thalamus in Wilson's disease using
      diffusion tensor imaging (DTI). MATERIALS AND METHODS: Fifteen patients with
      Wilson's disease and an abnormal signal in the thalamus (designated as group 1)
      and 18 patients with Wilson's disease with a normal-appearing thalamus
      (designated as group 2) at conventional magnetic resonance imaging (MRI) were
      recruited. Fifteen age-matched and sex-matched healthy volunteers were also
      enrolled as the control group (designated as group 3). The fractional anisotropy
      (FA), primary eigenvalue (lambda1), second eigenvalue (lambda2), and third
      eigenvalue (lambda3) of the thalamus were measured and the differences were
      compared. RESULTS: The FA values of the thalamus were different in the three
      groups (group 1: 0.36 +/- 0.02; group 2: 0.38 +/- 0.02; group 3: 0.43 +/- 0.02; F
      = 54.51, p < 0.001). A statistically significant difference was observed between
      group 1 and group 2 (p = 0.003), group 1 and group 3 (p = 0.001), and group 2 and
      group 3 (p < 0.001). The lambda1, lambda2, and lambda3 values of the thalamus
      were different in the three groups (1.11 +/- 0.06 mm(2)/s, 1.11 +/- 0.06 mm(2)/s,
      and 1.10 +/- 0.04 mm(2)/s of lambda1 in group 1, group 2, and group 3,
      respectively; 0.82 +/- 0.08 mm(2)/s, 0.78 +/- 0.05 mm(2)/s, and 0.72 +/- 0.02
      mm(2)/s of lambda2 in group 1, group 2, and group 3, respectively; 0.52 +/- 0.05
      mm(2)/s, 0.49 +/- 0.06 mm(2)/s, and 0.42 +/- 0.06 mm(2)/s of lambda3 in group 1,
      group 2, and group 3, respectively; F = 1.65, p = 0.203 of lambda1; F = 10.55, p
      < 0.001 of lambda2; F = 4.21, p = 0.021 of lambda3; respectively). A
      statistically significant difference in the lambda2 value was observed between
      group 1 and group 3 (p < 0.001) and group 2 and group 3 (p = 0.005). A
      statistically significant difference in the lambda3 value was also observed
      between group 1 and group 3 (p = 0.007). No significant difference in the lambda1
      value was noted between each of the two groups. CONCLUSIONS: Damage of the
      thalamus in Wilson's disease patients can be detected using DTI. DTI may provide
      information regarding thalamus damage in patients with Wilson's disease before
      abnormal signals on conventional MRI.

PMID- 24332167
TI  - 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) attenuates human
      platelet aggregation, secretion and spreading in vitro.
AB  - INTRODUCTION: 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside(THSG) is a water
      soluble component of the rhizome extract from the traditional Chinese herb
      Polygonum multiflorum. Recent studies have demonstrated that THSG has potent anti
      oxidative and anti-inflammatory effects. In this study, we investigated the anti
      platelet aggregation, secretion and spreading of THSG with different methods. The
      purpose was to explore the anti-platelet effect of THSG and the underlying
      mechanism. MATERIALS AND METHODS: We investigated the anti-platelet activity of
      THSG on platelet aggregation induced by collagen (2 MUg/mL), thrombin(0.04U/mL),
      U46619 (3 MUM) and ADP (2 MUM). ATP secretion induced by collagen (2 MUg/mL) was
      also investigated. P-selectin expression and PAC-1 binding were measured by flow
      cytometry. In addition, human platelet spreading on immobilized fibrinogen and
      immunoblotting were also tested. RESULTS: THSG dose-dependently inhibited
      platelet aggregation and ATP secretion induced by collagen. It inhibited platelet
      P-selectin expression and PAC-1 binding induced by thrombin(0.1U/mL). THSG also
      inhibited human platelet spreading on immobilized fibrinogen, a process mediated
      by platelet outside-in signaling. Western blot analysis showed that THSG could
      inhibit platelet Fc gamma RIIa, Akt(Ser473)and GSK3beta(Ser9) phosphorylation.
      CONCLUSIONS: Our study indicates that THSG has potent anti-platelet activity to
      collagen induced aggregation. THSG is likely to exert protective effects in
      platelet-associated thromboembolic disorders by modulating human platelet.

PMID- 24332166
TI  - Most expression and splicing changes in myotonic dystrophy type 1 and type 2
      skeletal muscle are shared with other muscular dystrophies.
AB  - The prevailing pathomechanistic paradigm for myotonic dystrophy (DM) is that
      aberrant expression of embryonic/fetal mRNA/protein isoforms accounts for most
      aspects of the pleiotropic phenotype. To identify aberrant isoforms in skeletal
      muscle of DM1 and DM2 patients, we performed exon-array profiling and RT-PCR
      validation on the largest DM sample set to date, including Duchenne, Becker and
      tibial muscular dystrophy (NMD) patients as disease controls, and non-disease
      controls. Strikingly, most expression and splicing changes in DM patients were
      shared with NMD controls. Comparison between DM and NMD identified almost no
      significant differences. We conclude that DM1 and DM2 are essentially identical
      for dysregulation of gene expression, and DM expression changes represent a
      subset of broader spectrum dystrophic changes. We found no evidence for
      qualitative splicing differences between DM1 and DM2. While some DM-specific
      splicing differences exist, most of the DM splicing differences were also seen in
      NMD controls. SSBP3 exon 6 missplicing was observed in all diseased muscle and
      led to reduced protein. We conclude there is no widespread DM-specific
      spliceopathy in skeletal muscle and suggest that missplicing in DM (and NMD) may
      not be the driving mechanism for the muscle pathology, since the same pathways
      show expression changes unrelated to splicing. 

PMID- 24332175
TI  - Macrolide-induced ribosomal frameshifting: a new route to antibiotic resistance.
AB  - In this issue of Molecular Cell, Gupta et al. (2013a) describe a novel,
      antibiotic-dependent ribosomal frameshifting event that activates translation of
      an antibiotic resistance gene.

PMID- 24332172
TI  - From the editor.

PMID- 24332173
TI  - Is it time we adopted a classification for parotid gland cytology?

PMID- 24332169
TI  - Local tumour progression after loco-regional therapy of hepatocellular
      carcinomas: value of fusion imaging-guided radiofrequency ablation.
AB  - AIM: To assess the value of fusion imaging of real-time ultrasonography (US) with
      liver computed tomography (CT)/magnetic resonance imaging (MRI) images for
      planning US of radiofrequency ablation (RFA) in improving conspicuity of the
      lesions and reducing false-positive detection of local tumour progression (LTP)
      found after transcatheter arterial chemoembolization (TACE) or RFA of
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was approved by
      the institutional review board and informed consent was waived. Fifty patients
      with LTP (mean +/- SD, 1.5 +/- 0.6 cm; range 0.5-3 cm) detected at follow-up CT
      or MRI were included. Planning US was performed by two radiologists using
      conventional US first and fusion imaging later in the same session. False
      positive detection rates were assessed using conventional US based on the results
      of fusion imaging. The number cases of initially invisible tumours on
      conventional US that became visible after image fusion were also evaluated. The
      true-positive detection rate and conspicuity scores of the index tumours were
      compared between conventional US and fusion imaging. RESULTS: On conventional US,
      40 (80%) out of 50 HCCs with LTP were identified. However, the false-positive
      detection rate of conventional US was 12.5% (5/40). Out of 10 initially invisible
      HCCs with LTP on conventional US, six (60%) became visible after image fusion.
      The true-positive detection rate on conventional US was 70% (35/50), whereas it
      was increased to 92% (46/50) after image fusion (p = 0.0026). CONCLUSION: Fusion
      imaging can improve the conspicuity of lesions and reduce the false-positive
      detection of LTP after TACE or RFA.

PMID- 24332180
TI  - [Basal cell carcinoma in a smallpox vaccination scar].

PMID- 24332181
TI  - [Bone and androgens].
AB  - Sexual steroids are major determinants of skeletal maturation and steady state.
      Estrogens are mandatory in both sexes. They induce endochondral bone formation
      and growth plate knitting. Androgens are mainly active in male. They increase
      length and radial bone growth. These differences explain the duality of
      biomechanics in both sexes. Deep androgen deficiency induces rapid bone loss and
      increases bone fracture risk. The androgen treatment of andropause has weak
      rationale. Androgens interact with bone metabolism within the medulla-bone unit.
      They activate the whole osteoblastic lineage and interact with preosteoclastic
      regulation. Androgens found their place in bone metabolism regulation through
      RANK/osteoprotegerin and Wnt/sclerostin pathways. 

PMID- 24332184
TI  - Nurse patient ratios, skill mix and work futures.

PMID- 24332165
TI  - Exploring the role of receptor flexibility in structure-based drug discovery.
AB  - The proper understanding of biomolecular recognition mechanisms that take place
      in a drug target is of paramount importance to improve the efficiency of drug
      discovery and development. The intrinsic dynamic character of proteins has a
      strong influence on biomolecular recognition mechanisms and models such as
      conformational selection have been widely used to account for this dynamic
      association process. However, conformational changes occurring in the receptor
      prior and upon association with other molecules are diverse and not obvious to
      predict when only a few structures of the receptor are available. In view of the
      prominent role of protein flexibility in ligand binding and its implications for
      drug discovery, it is of great interest to identify receptor conformations that
      play a major role in biomolecular recognition before starting rational drug
      design efforts. In this review, we discuss a number of recent advances in
      computer-aided drug discovery techniques that have been proposed to incorporate
      receptor flexibility into structure-based drug design. The allowance for receptor
      flexibility provided by computational techniques such as molecular dynamics
      simulations or enhanced sampling techniques helps to improve the accuracy of
      methods used to estimate binding affinities and, thus, such methods can
      contribute to the discovery of novel drug leads. 

PMID- 24332170
TI  - 3D CT cerebral angiography technique using a 320-detector machine with a time
      density curve and low contrast medium volume: comparison with fixed time delay
      technique.
AB  - AIM: To describe a cerebral computed tomography angiography (CTA) technique using
      a 320-detector CT machine and a small contrast medium volume (35 ml, 15 ml for
      test bolus). Also, to compare the quality of these images with that of the images
      acquired using a larger contrast medium volume (90 or 120 ml) and a fixed time
      delay (FTD) of 18 s using a 16-detector CT machine. MATERIALS AND METHODS:
      Cerebral CTA images were acquired using a 320-detector machine by synchronizing
      the scanning time with the time of peak enhancement as determined from the time
      density curve (TDC) using a test bolus dose. The quality of CTA images acquired
      using this technique was compared with that obtained using a FTD of 18 s (by 16
      detector CT), retrospectively. Average densities in four different intracranial
      arteries, overall opacification of arteries, and the degree of venous
      contamination were graded and compared. RESULTS: Thirty-eight patients were
      scanned using the TDC technique and 40 patients using the FTD technique. The
      arterial densities achieved by the TDC technique were higher (significant for
      supraclinoid and basilar arteries, p < 0.05). The proportion of images deemed as
      having "good" arterial opacification was 95% for TDC and 90% for FTD. The degree
      of venous contamination was significantly higher in images produced by the FTD
      technique (p < 0.001%). CONCLUSION: Good diagnostic quality CTA images with
      significant reduction of venous contamination can be achieved with a low contrast
      medium dose using a 320-detector machine by coupling the time of data acquisition
      with the time of peak enhancement.

PMID- 24332182
TI  - [Biomarkers in emergency medicine and critical care patients: advances and
      pitfalls for news tools].
AB  - The use of biomarkers has changed approach of diagnosis and treatment procedures
      in emergency medicine, especially in the field of cardiovascular disorders.
      Effectiveness of new strategies that integrate biomarkers has precluded
      development and research in novel tools that may improve safety and efficiency at
      bedside. This mini-review presents current knowledge on utility of biomarkers in
      emergency medicine, including data that should be taken into account to avoid
      misleading utilization. 

PMID- 24332179
TI  - [Prevalence of non-conventional cardiovascular risk factors in Tunisian
      diabetics].
AB  - BACKGROUND: The cardiovascular risk appears very early in the history of diabetes
      mellitus and is related not only to hyperglycemia but mainly to the other risk
      factors associated to diabetes mellitus. OBJECTIVE: To evaluate the prevalence of
      non-conventional cardiovascular risk factors in a Tunisian diabetic population.
      PATIENTS AND METHODS: The prospective study enrolled 120 type 2 diabetic patients
      recently diagnosed and 60 healthy people, sex and age matched. All have benefited
      from blood sampling in order to analyze biological parameters routinely
      undertaken in diabetes. Non-conventional cardiovascular risk factors were also
      determined such as: microalbuminuria of 24 hours, high sensitivity C-reactive
      protein (hs CRP), homocysteinemia, vitamin B12, folate and insulinemia. The
      participants have also benefited from abdominal echography to search nonalcoholic
      hepatic steatosis. RESULTS: Diabetics were aged 51.4 +/- 8.9 years in comparison
      with healthy people (50.1 +/- 6.39 years). A positive microalbuminuria was
      observed in 27.5% of diabetics versus 6.9% in healthy people (OR=5.1; P=0.001).
      The two third of diabetics had metabolic syndrome versus 25% of healthy people
      (OR=6.0; P<0.001) and insulinoresistance evaluated by HOMA-IR, was 3.4 +/- 0.2 in
      diabetics versus 2 +/- 0.1 in healthy people; P<0.001. HsCRP level was
      significantly higher in diabetics in comparison with healthy people (3.7 +/-
      0.2mg/L versus 1.9 +/- 0.3mg/L; P<0.001) and hyperhomocysteinemia was more
      frequently found in diabetics. Also, we noted that 69.6% of patients had hepatic
      steatosis versus only 24.6% of healthy people (OR=7.1; P<0.001). CONCLUSION: The
      non-conventional cardiovascular risk factors were more frequently found in early
      diagnosed type 2 diabetic patients than in healthy people. These non-conventional
      factors could be helpful in stratification of the cardiovascular risk level and
      also in the screening of ischemic heart diseases.

PMID- 24332174
TI  - Preventing bacterial suicide: a novel toxin-antitoxin strategy.
AB  - In this issue of Molecular Cell, Aarke et al. (2013) identify a toxin-antitoxin
      system in Caulobacter crescentus that acts by a unique mechanism. The toxin,
      which blocks DNA replication, is constitutively degraded by ClpXP, and this
      degradation requires the antitoxin, a ClpXP adaptor.

PMID- 24332176
TI  - Quaternary dynamics of the SecA motor drive translocase catalysis.
AB  - Most secretory preproteins exit bacterial cells through the protein translocase,
      comprising the SecYEG channel and the dimeric peripheral ATPase motor SecA.
      Energetic coupling to work remains elusive. We now demonstrate that translocation
      is driven by unusually dynamic quaternary changes in SecA. The dimer occupies
      several successive states with distinct protomer arrangements. SecA docks on
      SecYEG as a dimer and becomes functionally asymmetric. Docking occurs via only
      one protomer. The second protomer allosterically regulates downstream steps.
      Binding of one preprotein signal peptide to the SecYEG-docked SecA protomer
      elongates the SecA dimer and triggers the translocase holoenzyme to obtain a
      lower activation energy conformation. ATP hydrolysis monomerizes the triggered
      SecA dimer, causing mature chain trapping and processive translocation. This is a
      unique example of one protein exploiting quaternary dynamics to become a
      substrate receptor, a "loading clamp," and a "processive motor." This mechanism
      has widespread implications on protein translocases, chaperones, and motors.

PMID- 24332178
TI  - RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control
      cancer cell proliferation.
AB  - RBM5, a regulator of alternative splicing of apoptotic genes, and its highly
      homologous RBM6 and RBM10 are RNA-binding proteins frequently deleted or mutated
      in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the
      proliferative capacity of cancer cells and display distinct positional effects in
      alternative splicing regulation. We identify the Notch pathway regulator NUMB as
      a key target of these factors in the control of cell proliferation. NUMB
      alternative splicing, which is frequently altered in lung cancer, can regulate
      colony and xenograft tumor formation, and its modulation recapitulates or
      antagonizes the effects of RBM5, 6, and 10 in cell colony formation. RBM10
      mutations identified in lung cancer cells disrupt NUMB splicing regulation to
      promote cell growth. Our results reveal a key genetic circuit in the control of
      cancer cell proliferation.

PMID- 24332188
TI  - Clinical experience with CorMatrix extracellular matrix in the surgical treatment
      of mitral valve disease.
AB  - OBJECTIVES: To determine the clinical utility of an acellular bioscaffold as a
      structural material for mitral valve repair (MVr). METHODS: This was a
      retrospective study of patients undergoing partial or subtotal leaflet
      replacement and/or leaflet extension to treat mitral regurgitation or acute
      endocarditis and/or reconstruction of atrial-ventricular continuity after annular
      decalcification. The material used for repair was a bioresorbable extracellular
      matrix (ECM) material indicated for cardiac tissue repair (CorMatrix
      Cardiovascular, Inc, Roswell, Ga). After the necessary debridement, the ECM
      bioscaffold was tailored and sewn to the native mitral valve tissue.
      Intraoperative photographs and serial, follow-up echocardiograms were used for
      evaluation. RESULTS: From September 2008 to February 2013, MVr requiring the
      addition of patch material was performed in 19 patients. The median
      echocardiographic follow-up was 10.9 months (range, 4 days to 48 months). One
      early and 2 late deaths were unrelated to MVr. No perioperative or late strokes
      occurred. Two patients with a history of cancer, chemotherapy, and radiotherapy
      experienced failure of the initial MVr, necessitating reintervention. The other
      MVrs continued to show good valvular function and no calcification on
      echocardiographic follow-up of 4 days to 48 months. CONCLUSIONS: The ECM
      bioscaffold is a satisfactory material for MVr in a variety of surgical
      situations, including endocarditis. It appears to resist calcification and
      infection. Additional studies are warranted to determine the long-term durability
      of repairs made with ECM, and its appropriate use in patients who have previously
      undergone radiotherapy or chemotherapy.

PMID- 24332187
TI  - Early postoperative bleeding is independently associated with increased surgical
      mortality in infants after cardiopulmonary bypass.
AB  - OBJECTIVE: Infants undergoing cardiac surgery often have postoperative bleeding
      contributing to the occurrence of adverse events. A quantitative evaluation of
      postoperative bleeding has not been well described. METHODS: We identified 1071
      infants who had undergone cardiopulmonary bypass from August 1, 2008 to December
      31, 2011. The volume of postoperative bleeding and its effect on mortality were
      reviewed. RESULTS: Postoperative bleeding during the first 12 hours
      postoperatively was stratified by quartiles. Bleeding was significantly
      associated with increased mortality (odds ratio [OR], 1.15; 95% confidence
      interval [CI] 1.10-1.21; P < .001). Other risk factors significantly associated
      with mortality included greater Risk Adjustment for Congenital Heart Surgery
      score (OR, 1.5; 95% CI, 1.22-1.85; P < .001), single ventricle anatomy (OR, 3.09;
      95% CI, 1.68-5.67; P < .001), younger age (OR, 0.99; 95% CI, 0.98-0.99; P <
      .001), and longer perfusion time (OR, 1.01; 95% CI, 1.01-1.02; P < .001).
      Subjects with greater bleeding volumes experienced a longer postoperative
      mechanical ventilation and intensive care unit stay. The overall hospital
      mortality was 4.1%. On multivariate analysis, adjusting for age, single ventricle
      anatomy, Risk Adjustment for Congenital Heart Surgery score, and perfusion time,
      an increasing bleeding volume was independently associated with increased
      mortality. Packed red blood cell transfusion was independently associated with an
      increased duration of mechanical ventilation (P = .01) and intensive care unit
      length of stay (P = .003). CONCLUSIONS: Early postoperative hemorrhage was
      independently associated with an increased mortality in infants after cardiac
      surgery. The longer interval from surgery to death suggests that other factors,
      aside from the bleeding itself, including the transfusion volume, might
      contribute to mortality. Initiatives to limit postoperative bleeding and to
      critically appraise packed red blood cell transfusion practices are warranted.

PMID- 24332185
TI  - Temporal rearrangement of pre-ictal PTZ induced spike discharges by low frequency
      electrical stimulation to the amygdaloid complex.
AB  - BACKGROUND: Epilepsy is a common neurological disease affecting over 40 million
      people worldwide. The foremost important challenge of epileptologists has been to
      control and predict the recurrent and spontaneous seizures of epileptic patients.
      The application of low frequency electrical stimulation (LFS) in deep brain
      structures has shown promising results in seizure control. However, the use of
      LFS as a probing strategy for seizure prediction, thus contributing to a closed
      loop solution, is still poorly explored. OBJECTIVE: To improve seizure prediction
      by producing gradually increasing phase-locked pre-ictal electrographical
      responses, due to the short-term plastic changes in epileptogenic neural
      networks, thus behaving as a "programmed" surrogate marker. METHODS: Urethane
      anesthetized rats were divided into 3 groups: the PTZ-noES group was injected
      with pentylenetetrazole (PTZ 4 mg/ml/min flow rate) i.v. without electrical
      stimulation (ES); the ES-noPTZ group received ES (0.5 Hz, 0.1 ms pulse width and
      0.6 mA) to the amygdaloid complex and the PTZ + ES group received simultaneously
      i.v. PTZ infusion and ES. After each condition, electrographical parameters and c
      Fos expression of regions of interest were evaluated. RESULTS: Although the PTZ +
      ES group had no evident change in the sustained electrographic seizure onset,
      duration and/or frequency spectrum; c-Fos labeling showed a different expression
      pattern when compared to the PTZ-noES and ES-noPTZ. Also, PTZ + ES formed a
      gradually increasing evoked potential; confirming the strong coupling of
      reverberant neural networks induced by ES - phase locked to stimuli. CONCLUSION:
      ES induces a detectable temporal rearrangement of pre-ictal activity, which has
      suggestive applicability to seizure prediction.

PMID- 24332171
TI  - Hepatic tumours in children with biliary atresia: single-centre experience in 13
      cases and review of the literature.
AB  - AIM: To establish the risks of developing of hepatic tumours and to investigate
      their clinical and imaging findings in children with biliary atresia (BA) after
      Kasai portoenterostomy (Kasai). MATERIALS AND METHODS: Among 157 children who had
      undergone Kasai for BA over an 18 year period, patients who had newly developed
      hepatic tumours were identified. Patient demographics, clinical features, and
      imaging findings were retrospectively reviewed. RESULTS: Three male and 10 female
      patients (mean age 3.9 years) all (8%, of 157) had single hepatic tumours, which
      were confirmed in 10 explanted and three non-explanted livers. Ten (77%) were
      benign and three (23%) were malignant. Of the benign hepatic tumours, focal
      nodular hyperplasia (FNH; n = 6) was the most common, followed by regenerative
      nodules (n = 3) and adenoma (n = 1). All FNH appeared in young children <1 year
      of age and showed a subcapsular location, bulging contour, and lack of central
      scar. Malignant tumours included two hepatocellular carcinomas and one
      cholangiocarcinoma. CONCLUSION: Hepatic tumours developed in approximately 8% of
      children with BA after Kasai. Although benign tumours, including FNHs and
      regenerative nodules, were more common than malignant tumours, screening with
      alpha-foetoprotein (AFP) levels and regular imaging studies are the mainstay of
      malignant tumour detection.

PMID- 24332183
TI  - [Intrauterine upper limb ischemia due to a heterozygous mutation (677C>T) of the
      methylene-tetrahydrofolatereductase gene].
AB  - Limb ischemia rarely occurs in utero. The diagnosis can be made by clinical
      observation at birth or a few hours later. Color duplex ultrasound is the first
      imaging test used to confirm the diagnosis. The etiology appears to be complex
      and multifactorial. We report 2 cases of intrauterine limb ischemia involving the
      upper limb in 2 newborns. Both children were heterozygous for the 5,10
      methylenetetrahydrofolate reductase 677C>T gene variant. The first patient was
      born by caesarean section at 34 weeks of gestation. At delivery, the infant
      presented with pallor in his right upper limb and weak radial arterial pulsation.
      Doppler ultrasound and computed tomography angiography demonstrated a totally
      occlusive thrombus within the right brachial artery. The newborn underwent
      systemic thrombolysis with good recovery. The second patient was born via
      cesarean section at 37 weeks of gestation. At delivery, the infant presented with
      a motionless, cold, and gangrenous right upper limb. The demarcation line was
      just below the right elbow. Doppler ultrasound revealed a complete occlusion of
      the right subclavian artery. After failure of antithrombotic therapy, the limb
      was amputated with no further complication. We discuss the epidemiology,
      etiology, and clinical features of this rare pathology.

PMID- 24332186
TI  - Functional impact of transmitral gradients at rest and during exercise after
      restrictive annuloplasty for ischemic mitral regurgitation.
AB  - OBJECTIVES: Restrictive mitral valve annuloplasty combined with coronary artery
      bypass grafting is the treatment of choice for ischemic mitral regurgitation.
      Postoperative functional mitral stenosis and its potential impact on functional
      capacity remain the object of debate. The aim of this study was to assess
      functional and hemodynamic outcome at rest and during exercise in a population
      with ischemic mitral regurgitation after a standardized restrictive mitral valve
      annuloplasty. METHODS: A total of 23 patients with ischemic mitral regurgitation
      who were previously treated with coronary artery bypass grafting and restrictive
      mitral valve annuloplasty underwent a semi-supine (bicycle) exercise test with
      Doppler echocardiography and ergospirometry. The surgical technique was identical
      in all patients, using a complete semi-rigid ring downsized by 2 sizes after
      measuring the height of the anterior mitral leaflet, to achieve a coaptation
      length of at least 8 mm. RESULTS: At a mean follow-up of 28 +/- 15 months, mean
      transmitral gradients at rest and maximal exercise were 4.4 +/- 1.8 mm Hg and 8.2
      +/- 4.2 mm Hg, respectively (P < .001). Transmitral gradients did not correlate
      with exercise capacity (maximal oxygen uptake) or pulmonary artery pressures.
      Patients with a resting mean gradient of 5 mm Hg or greater (n = 9) reached a
      significantly higher maximal oxygen uptake; however, they had a better ejection
      fraction and cardiac output at rest and reached a higher cardiac output at peak
      exercise. CONCLUSIONS: Transmitral gradients after restrictive mitral valve
      annuloplasty for ischemic mitral regurgitation did not correlate with functional
      capacity as measured by maximal oxygen uptake during semi-supine bicycle testing.
      Functional capacity and transmitral gradients are determined not only by the
      severity of mitral stenosis but also by hemodynamic factors, such as ejection
      fraction and cardiac output. Transmitral gradients should be interpreted with
      respect to patient hemodynamics and not necessarily be considered as detrimental
      for functional capacity.

PMID- 24332177
TI  - Epigenetic regulation of the miR142-3p/interleukin-6 circuit in glioblastoma.
AB  - Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis.
      However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor
      progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits
      miR142-3p expression and promotes GBM propagation by inducing DNA
      methyltransferase 1-mediated hypermethylation of the miR142-3p promoter.
      Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3' UTR
      of IL-6. In addition, miR142-3p also targets the 3' UTR and suppresses the
      expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of
      Sox2-related stemness. We further show that HMGA2 enhances Sox2 expression by
      directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors
      present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated
      miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of
      miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties
      in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p
      feedback-loop-dependent regulation of GBM malignancy that could be a potential
      therapeutic target.

PMID- 24332189
TI  - Clinical, biochemical, and genetic predictors of coronary artery bypass graft
      failure.
AB  - OBJECTIVES: To identify novel predictors for coronary artery bypass grafting
      failure, we probed for associations with known clinical and biochemical risk
      factors for atherosclerosis. We also used microarray analysis to identify novel
      single nucleotide polymorphisms to better understand the genetics and
      pathogenesis of graft occlusion. METHODS: The present study was a nested case
      control substudy of the Radial Artery Patency Study 5-year follow-up data. From
      1996 to 2001, 87 patients underwent coronary artery bypass grafting. Of these, 26
      patients (29.9%) had an occluded study graft (saphenous vein or radial artery) at
      8.0 +/- 1.1 years. The clinical parameters, late angiography, blood biomarker
      levels, and surgical outcomes data were included in a multivariate analysis to
      determine the independent predictors of graft failure. RESULTS: The risk factors
      of graft failure were fibrinogen (odds ratio [OR], 3.94; 95% confidence interval
      [CI], 1.33-11.63; P = .01), creatinine (OR, 1.06; 95% CI, 1.02-1.10; P = .006),
      and diabetes mellitus (OR, 5.15; 95% CI, 1.08-24.59; P = .04). High-density
      lipoprotein (OR, 0.74; 95% CI, 0.53-1.02; P = .06) was weakly protective;
      however, low-density lipoprotein and total cholesterol were not predictors. We
      then identified the association of several human single nucleotide polymorphisms
      with graft failure, including mutations in glutathione-S-transferase alpha3.
      Human coronary arteries and bypass grafts demonstrated increased protein
      expression of glutathione-S-transferase alpha3, a known cardioprotective factor,
      in the atherosclerotic regions and surrounding adventitial tissues. CONCLUSIONS:
      We identified diabetes as a potential clinical predictor and plasma fibrinogen,
      creatinine, and high-density lipoprotein as potential novel biomarkers. These
      might help risk stratify patients for the development of graft failure. We also
      demonstrated a novel association between glutathione-S-transferase alpha3 and
      graft failure.

PMID- 24332192
TI  - Validating two self-report physical activity measures in middle-aged adults
      completing a group exercise or home-based physical activity program.
AB  - OBJECTIVES: To compare self-reported physical activity recorded in physical
      activity diaries or the Active Australia Survey with objectively measured
      physical activity using accelerometry in sedentary middle-aged adults completing
      two physical activity interventions. DESIGN: Cross-sectional study. METHODS:
      Sedentary 50-65 year olds were recruited to a non-randomized 6-month community
      group exercise program (G) or a physiotherapist-led home-based physical activity
      program (HB). Over 7-days, 76 participants (HB 39, G 37) wore an ActiGraph GT1M
      accelerometer (5s epochs), completed the Active Australia Survey (AAS) and a
      daily physical activity diary. Data were analysed using descriptive statistics
      and Spearman rank-order correlations. RESULTS: The two interventions had similar
      demographic and physical activity characteristics except that home-based
      participants were younger (p < 0.01), more likely to be employed full time (p <=
      0.001) and reported less moderate-to-vigorous physical activity in the physical
      activity diaries compared to group exercise participants (HB 29 +/- 21 min d(-1)
      vs. G 57 +/- 35 min d(-1), p <= 0.001). Home-based participants had fair-to-good
      agreement between the physical activity diaries and AAS or ActiGraph data (r =
      0.39-0.68, p < 0.05). Group exercise physical activity diary data did not
      correlate significantly with either the AAS or ActiGraph data. In contrast, group
      exercise AAS data had good correlations with ActiGraph data (r = 0.49-0.64, p <=
      0.001). CONCLUSIONS: Physical activity diaries should be interpreted cautiously
      unless intervention participants have an adequate understanding of physical
      activity intensity. The AAS is the preferred self-report measure in middle-aged
      adults independent of intervention.

PMID- 24332191
TI  - Defining the best practice patterns for the neonatal systemic-to-pulmonary artery
      shunt procedure.
AB  - OBJECTIVES: To assess variation in outcome measures and their associations with
      shunt thrombosis prophylaxis regimens after systemic-to-pulmonary artery shunt
      surgery across centers in the United States participating in the Pediatric Health
      Information System database. METHODS: We reviewed data on neonates who underwent
      an off-pump shunt procedure at 39 centers between 2000 and 2011. The overall
      variation in rates of discharge mortality and shunt-related complications were
      assessed by funnel plots. Complications were defined as revision/repeat of the
      shunt procedure during the same admission, institution of extracorporeal membrane
      oxygenation after surgery, and catheter interventions after shunt surgery.
      Bayesian hierarchical modeling was used to identify outliers. Shunt thrombosis
      prophylaxis regimens including the time of initiation of aspirin were compared
      between high and low outliers. RESULTS: A total of 2058 index operations were
      identified. Funnel plots highlighting the outcomes from various centers allowed
      discrimination of discharge mortality and complication rates around an aggregate
      of 6.7% and 12.3%, respectively. Bayesian modeling showed the presence of
      substantial variation in complication rates between centers; 20% of them were
      identified as outliers. Aspirin was initiated significantly earlier during the
      hospital course in centers with a lower composite rate of complications than
      those with higher rates (median initiation day of 2 [interquartile range (IQR), 1
      3] in low outliers vs 4 [IQR, 3-6] in high outliers; P < .001). CONCLUSIONS: A
      substantial variation was found between hospitals in the rate of shunt-related
      complications. Centers with best outcomes implement aspirin earlier in their
      postoperative shunt thrombosis prophylaxis regimen.

PMID- 24332193
TI  - Diversity and activity of methanotrophs in landfill cover soils with and without
      landfill gas recovery systems.
AB  - Aerobic CH4 oxidation plays an important role in mitigating CH4 release from
      landfills to the atmosphere. Therefore, in this study, oxidation activity and
      community of methanotrophs were investigated in a subtropical landfill. Among the
      three sites investigated, the highest CH4 concentration was detected in the
      landfill cover soil of the site (A) without a landfill gas (LFG) recovery system,
      although the refuse in the site had been deposited for a longer time (~14-15
      years) compared to the other two sites (~6-11 years) where a LFG recovery system
      was applied. In April and September, the higher CH4 flux was detected in site A
      with 72.4 and 51.7gm(-2)d(-1), respectively, compared to the other sites. The
      abundance of methanotrophs assessed by quantification of pmoA varied with
      location and season. A linear relationship was observed between the abundance of
      methanotrophs and CH4 concentrations in the landfill cover soils (R=0.827,
      P<0.001). The key factors influencing the methanotrophic diversity in the
      landfill cover soils were pH, the water content and the CH4 concentration in the
      soil, of which pH was the most important factor. Type I methanotrophs, including
      Methylococcus, Methylosarcina, Methylomicrobium and Methylobacter, and type II
      methanotrophs (Methylocystis) were all detected in the landfill cover soils, with
      Methylocystis and Methylosarcina being the dominant genera. Methylocystis was
      abundant in the slightly acidic landfill cover soil, especially in September, and
      represented more than 89% of the total terminal-restriction fragment abundance.
      These findings indicated that the LFG recovery system, as well as physical and
      chemical parameters, affected the diversity and activity of methanotrophs in
      landfill cover soils. 

PMID- 24332190
TI  - Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo:
      implications for novel left ventricular assist devices with a peripheral
      anastomosis.
AB  - OBJECTIVES: Less invasive circulatory support devices have been developed that
      require anastomosis to a peripheral artery. The Symphony Heart Assist System
      (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the
      subclavian artery to provide partial circulatory support. The surgical
      configuration produces nonphysiologic blood pressure and bidirectional flow in
      the subclavian artery. Our objective was to identify effects of altered
      hemodynamics on arterial structure and function. METHODS: In calves (n = 23; 80
      100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely,
      carotid blood pressure and flow were recorded to evaluate hemodynamic changes.
      After medium-term support (1-4 weeks), carotid artery was studied. Histologic and
      molecular assays evaluated architectural changes. Quantitative real-time
      polymerase chain reaction evaluated gene expression of matrix metalloproteinase
      (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial
      ring studies evaluated physiologic responses. RESULTS: During Symphony support,
      carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased
      significantly (P < .05) from 1.40 +/- 0.32 to 4.29 +/- 0.33 L/min. Flow during
      native cardiac diastole reversed completely from 0.25 +/- 0.05 to -4.15 +/- 0.38
      L/min in carotid artery proximal to the anastomosis. After medium-term support,
      the carotid artery was significantly dilated with significantly thinner tunica
      media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene
      expression decreased significantly, connective tissue growth factor gene
      expression increased significantly, and collagen, elastin, and total
      extracellular matrix increased significantly. Endothelial cells were
      significantly hypertrophied and produced significantly more von Willebrand
      factor. Endothelial apoptosis increased significantly. Platelet-endothelial
      interactions decreased significantly. Endothelial-independent contraction
      decreased significantly, whereas endothelial-dependent relaxation increased
      modestly. CONCLUSIONS: Assisted circulation with a left ventricular assist device
      triggered arterial remodeling that allowed a peripheral artery to accommodate the
      altered hemodynamics of a novel partial-support pump. Further delineation of
      remodeling pathways may be of significance for the emerging field of partial
      circulatory support.

PMID- 24332195
TI  - Reflections on 2013, the beginning of 2014, and the Food and Drug
      Administration's new expedited approval program known as breakthrough product
      designation.

PMID- 24332196
TI  - Pharmacokinetic and safety profile of ivabradine in healthy Chinese men: a phase
      I, randomized, open-label, increasing single- and multiple-dose study.
AB  - BACKGROUND: Ivabradine is a pure heart rate-lowering agent that acts by
      inhibiting I(f), an important ionic current involved in pacemaker activity in the
      cells of the sinoatrial node. In the 2012 European Society of Cardiology
      Guidelines on Heart Failure, it was recommended that patients with a persistently
      high heart rate, despite treatment with an evidence-based dose of a beta-blocker,
      should be considered for treatment with ivabradine. OBJECTIVE: The aim of this
      study was to explore the pharmacokinetic/pharmacodynamic properties and safety
      profile of ivabradine in healthy Chinese men. METHODS: This Phase I, randomized,
      open-label, parallel-arm, single- and multiple-dose study was conducted at the
      Clinical Pharmacology Center of the Cardiovascular Institute and Fu Wai Hospital
      at the Chinese Academy of Medical Sciences & Peking Union Medical College in
      Beijing, People's Republic of China. Healthy, nonsmoking volunteers were randomly
      assigned to 1 of 3 treatment groups based on treatment with 5, 10 or 20 mg of
      ivabradine. After a single dose, the subjects assigned to the 3 dose groups
      received repeated oral doses of ivabradine BID for 6 days. The plasma
      concentrations of ivabradine were determined by using a HPLC-MS/MS method.
      Systolic and diastolic blood pressure and heart rate measurements were taken, and
      ECG and Holter monitoring was performed. Tolerability was assessed throughout the
      study by physical and ophthalmologic examinations, vital signs measurement,
      laboratory analyses, and monitoring of adverse effects. RESULTS: A total of 36
      healthy Chinese men were enrolled in the study. After the single dose, plasma
      ivabradine Cmax and AUC increased approximately linearly with dosage, no
      statistically significant differences were found in t1/2 or Tmax between the dose
      groups. After multiple doses, there was no significant change in Tmax compared
      with the results after a single dose. After repeated doses, t1/2, Cmax, and AUC
      increased significantly (P < 0.001). After a single dose, a significant reduction
      in heart rate at 2 hours' postdose was observed in the highest dose group,
      whereas after repeated doses, a significant reduction in heart rate was observed
      from 2 to 4 hours' postdose for all 3 groups. The mean (SD) heart rate after
      repeated doses decreased 12.5 (4.8), 12.4 (6.9), and 20.5 (5.8) beats/min for the
      5-, 10-, and 20-mg dose groups, respectively. No clear trend in the changes in
      QTc, systolic and diastolic blood pressures, or respiration rate was observed.
      Ivabradine was well tolerated in these healthy Chinese men. CONCLUSIONS: The
      results of the study in a small population of healthy Chinese men suggest that
      the PK properties of ivabradine are linear with respect to dosing. After single
      and repeated oral administration of ivabradine, a significant decrease in heart
      rate was observed. Ivabradine appeared well tolerated in the population studied.
      Trial identifier: ACTRN1261300027741.

PMID- 24332199
TI  - Congenital familial subglottic stenosis: a case series and review of literature.
AB  - Subglottic stenosis is a narrowing of the endolarynx and maybe classified as
      congenital (primary) or acquired (secondary). Congenital stenosis maybe caused by
      a small cricoid cartilage, thick submucosa or other laryngeal abnormalities and
      remains a well-known cause of stridor in infancy. It occurs sporadically and
      familial occurrence is rare. Our case series identifies three children with
      congenital subglottic stenosis born to consanguineous parents. Congenital
      subglottic stenosis in siblings of unrelated parents has been previously
      reported, but not in consanguineous parents indicating a strong genetic link. We
      recommend further genetic research to assess the mode of possible heritage in
      this disease. 

PMID- 24332198
TI  - Endoscopic repair of laryngotracheoesophageal clefts: experience in 17 cases.
AB  - OBJECTIVE: To review the presentation and evaluation of laryngotracheoesophageal
      clefts as well as their treatment modalities, especially endoscopic closure.
      STUDY DESIGN: retrospective case series. METHODS: All patients treated for
      laryngotracheoesophageal clefts in our clinic during the last 15 years were
      included. Analysis of preoperative data, surgical success and functional outcome
      was performed. RESULTS: A total of 18 patients were included in our study. Cleft
      distribution was: type I (n=1), type II (n=3), type IIIa (n=5), type IIIb (n=8)
      and type IVa (n=1). All clefts were closed endoscopically by CO2 laser repair
      except for two patients who benfited from open surgery (one type I, one type
      IIIb). 7 of our 18 patients (39%) experienced a complication necessitating
      reoperation. Surgical treatment of LTEC allowed cessation of feeding tube
      assistance and artificial ventilation in 47% and 42% of patients respectively.
      CONCLUSION: Surgical treatement of laryngotracheoesophageal clefts remains a
      complex procedure with a high rate of morbidity for high grade clefts. Post
      surgical difficulties in feeding and breathing are associated with concomitant
      congenital anomalies. Endoscopic repair is a successful technique for treating up
      to grade IIIa laryngeal clefts. Further investigation is needed to assess the
      best approach for treating longer clefts.

PMID- 24332203
TI  - Hemophilic arthropathy: a review of imaging and staging.
AB  - Hemophilic arthropathy (HA) contributes the greatest morbidity and cost in the
      hemophilic population. Imaging plays a crucial role in accurately monitoring the
      disease process in all phases and evaluating treatment. It has been shown that
      prophylactic factor VIII replacement therapy, if given early in life, can prevent
      or delay the progression of HA and reduce the frequency of hemarthroses. This
      review evaluates the role of the different imaging modalities used in the staging
      of HA. It is noteworthy that a new refined consensus magnetic resonance imaging
      scale for assessment of HA has recently been published which together with
      introduction of semiquantitative scoring systems in ultrasound will help to
      provide a more tailored approach to the management of HA in the future. 

PMID- 24332201
TI  - Letter from the editor: Radiologic imaging in hematological disorders.

PMID- 24332194
TI  - Lipidomics in the analysis of malignancy.
AB  - Lipidomic methodologies have developed such that determination in lipid species
      content of cells and tissues is increasingly achievable. Adoption of these
      methods is highlighting the physiological importance of individual lipid
      molecular species rather than changes in an overall lipid class. In this article
      the use of such methodologies is considered and the potential for understanding
      the importance of lipid changes in malignancy assessed. 

PMID- 24332197
TI  - Salivary gland malignancies in children.
AB  - With an annual incidence of less than 1 per million, salivary gland malignancies
      in children are rare, constituting less than 10% of pediatric head and neck
      cancer. Although over 20 histologic types of salivary gland cancer have been
      reported in adults, a smaller number have been observed in the pediatric
      population. Mucoepidermoid carcinoma is the most common histologic type, followed
      by acinic cell carcinoma. Since the majority of salivary gland carcinomas are
      diagnosed at an early stage, the overall prognosis is often favorable with
      complete surgical resection. To date, no prospective or retrospective data
      comparing outcomes of surgery alone versus multimodality therapy in the
      management of salivary gland malignancies in the pediatric population exists.
      Consequently, management decisions are made on a case-by-base basis, taking
      prognosis, treatment-related morbidity, and long-term sequelae into account. 

PMID- 24332204
TI  - Lymphoproliferative lung disorders: a radiologic-pathologic overview. Part I:
      Reactive disorders.
AB  - Lymphoid tissue is a normal component of the lung and manifests as intrapulmonary
      lymph nodes, bronchus-associated lymphoid tissue (BALT), peripheral lymphocytic
      aggregates, solitary lymphocytes, and phagocytic cells. Pulmonary lymphoid
      lesions are thought to develop as a consequence of anomalous stimulation and
      response of the bronchus-associated lymphoid tissue and manifests as a spectrum
      of lymphoproliferative disorders that may be reactive or neoplastic. Reactive
      disorders are polyclonal abnormalities and include nodular lymphoid hyperplasia,
      lymphocytic interstitial pneumonia, follicular bronchiolitis, angiofollicular
      hyperplasia, and enlarged intrapulmonary lymph nodes. Affected patients are often
      asymptomatic. Imaging findings include focal nodules, diffuse bilateral
      centrilobular nodules, and hilar or mediastinal masses. 

PMID- 24332206
TI  - Imaging findings of hematologic diseases affecting the breast.
AB  - The breast is an uncommon manifestation site for malignant hematological
      diseases. Intramammary relapse can occur as an isolated tumor or as an
      extramedullary manifestation in systemic disease. Most published data regarding
      breast involvement in lymphoma or leukemia focus on the histopathologic
      characteristics of breast lymphoma or leukemia and do not describe radiological
      findings. Therefore, the purpose of this review is to provide statistical,
      clinical, and radiological information on hematological malignancies of the
      breast. 

PMID- 24332200
TI  - Role of forest conservation in lessening land degradation in a temperate region:
      the Monarch Butterfly Biosphere Reserve, Mexico.
AB  - With international concern about the rates of deforestation worldwide, particular
      attention has been paid to Latin America. Forest conservation programmes in
      Mexico include Payment for Environmental Services (PES), a scheme that has been
      successfully introduced in the Monarch Butterfly Biosphere Reserve. To seek
      further evidence of the role of PES in lessening land degradation processes in a
      temperate region, the conservation state of the Cerro Prieto ejido within the
      Reserve was assessed by an analysis of changes in vegetation cover and land-use
      between 1971 and 2013. There were no changes in the total forest surface area,
      but the relative proportions of the different classes of cover density had
      changed. In 1971, closed and semi-closed forest occupied 247.81 ha and 5.38 ha,
      82.33% and 1.79% of the total area of the ejido, respectively. By 2013, closed
      forest had decreased to 230.38 ha (76.54% of the ejido), and semi-closed cover
      was 17.23 ha (5.72% of the ejido), suggesting that some semi-closed forest had
      achieved closed status. The final balance between forest losses and recovery was:
      29.63 ha were lost, whereas 13.72 ha were recovered. Losses were mainly linked to
      a sanitation harvest programme to control the bark beetle Scolytus mundus.
      Ecotourism associated with forest conservation in the Cerro Prieto ejido has been
      considered by inhabitants as a focal alternative for economic development.
      Consequently, it is essential to develop a well-planned and solidly structured
      approach based on social cohesion to foster a community-led sustainable
      development at local level.

PMID- 24332205
TI  - Lymphoproliferative lung disorders: a radiologic-pathologic overview. Part II:
      Neoplastic disorders.
AB  - Lymphoproliferative pulmonary neoplasms can occur as primary pulmonary lymphomas
      or because of secondary pulmonary involvement. Neoplastic disorders may be
      difficult to differentiate from reactive pulmonary lymphoproliferative disorders,
      and immunohistochemical evaluation is often required to differentiate the 2 types
      of lesions. Neoplastic lymphoproliferative disorders are monoclonal lesions. Most
      affected patients present with systemic complaints, and imaging findings
      typically include nodules, masses, and lymphadenopathy. Primary pulmonary
      lymphomas are rare and account for less than 4% of the lymphomas that arise in
      extranodal sites. Secondary pulmonary lymphomas can affect the lung via
      hematogenous dissemination or by secondary involvement from tumor in adjacent or
      contiguous sites. Neoplastic lymphoproliferative lesions also include leukemia
      and plasma cell neoplasms. Posttransplantation lymphoproliferative disorders
      constitute a special type of lymphoid proliferation occurring in the setting of
      the chronic immunosuppression required for solid organ and bone marrow
      transplantation. 

PMID- 24332207
TI  - Imaging of primary gastrointestinal lymphoma.
AB  - Primary gastrointestinal (GI) lymphoma most often arises from stomach, small
      bowel, or colon. The 2 most common subtypes of primary GI lymphoma include low
      grade mucosa-associated lymphoid tissue lymphoma, strongly associated with
      Helicobacter pylori infection, and high-grade diffuse, large B-cell lymphoma.
      Primary GI lymphoma demonstrates a myriad of imaging manifestations that can
      commonly mimic other pathologies. Timely and accurate diagnosis remains important
      because treatment and prognosis of primary GI lymphoma differ significantly from
      other GI malignancies and even lymphoma of other primary sites. 

PMID- 24332202
TI  - The current state of imaging pediatric hemoglobinopathies.
AB  - The hemoglobinopathies are a group of genetic disorders with a broad spectrum of
      clinical manifestations and radiologic findings. The imaging of pediatric
      hemoglobinopathies, which is influenced by concomitant hemosiderosis and the
      sequela of chelation therapy, has evolved over the years along with ever
      improving technology. This article reviews and illustrates the most common
      radiographic and cross-sectional imaging findings of the 2 best known and
      clinically relevant hemoglobinopathies in pediatric patients, sickle cell disease
      and beta-thalassemia. 

PMID- 24332208
TI  - Imaging of multiple myeloma: usefulness of MRI and PET/CT.
AB  - Multiple myeloma is a heterogeneous hematologic disorder of plasma cells with
      varied bone marrow imaging appearances. With advancements in both treatment and
      use of advanced imaging over the last several decades, it is important for
      radiologists to recognize the imaging presentation of the disease and the staging
      implications of imaging. This paper reviews the staging as it relates to imaging,
      consensus recommendations for imaging, expected imaging appearances of myeloma,
      pitfalls, and complications associated with treatment that are demonstrable on
      imaging. 

PMID- 24332209
TI  - Update on pediatric leukemia and lymphoma imaging.
AB  - Together, leukemia and lymphoma account for half of all childhood malignancies.
      Leukemia and lymphoma arise from similar cell lines and can have overlapping
      imaging features; however, the clinical presentation, imaging strategies, and
      treatment protocols can vary substantially based on the specific subtype.
      Although imaging does not play a central role in staging or monitoring disease in
      childhood leukemia, findings on imaging may be the first indication of the
      diagnosis. Advanced imaging, especially positron emission tomography/computed
      tomography, has moved to the forefront of staging and treatment response
      evaluation in Hodgkin's disease and non-Hodgkin's lymphoma. Imaging also plays a
      key role in evaluating the myriad of treatment complications that are commonly
      seen with chemotherapy and associated neutropenia. Future efforts will be largely
      focused on decreasing radiation exposure to these children, utilizing reduced or
      radiation-free modalities, such as positron emission tomography/magnetic
      resonance and diffusion-weighted whole-body imaging with background suppression,
      as well as refining surveillance imaging strategies. The purpose of this article
      is to briefly review the classification of pediatric leukemia and lymphoma,
      illustrate common imaging findings at presentation throughout the body, describe
      staging and therapeutic response evaluation, and show a spectrum of commonly
      encountered complications of treatment. 

PMID- 24332210
TI  - Investigating the potential impact of four-dimensional computed tomography (4DCT)
      on toxicity, outcomes and dose escalation for radical lung cancer radiotherapy.
AB  - AIMS: To investigate the potential dosimetric and clinical benefits predicted by
      using four-dimensional computed tomography (4DCT) compared with 3DCT in the
      planning of radical radiotherapy for non-small cell lung cancer. MATERIALS AND
      METHODS: Twenty patients were planned using free breathing 4DCT then
      retrospectively delineated on three-dimensional helical scan sets (3DCT). Beam
      arrangement and total dose (55 Gy in 20 fractions) were matched for 3D and 4D
      plans. Plans were compared for differences in planning target volume (PTV)
      geometrics and normal tissue complication probability (NTCP) for organs at risk
      using dose volume histograms. Tumour control probability and NTCP were modelled
      using the Lyman-Kutcher-Burman (LKB) model. This was compared with a predictive
      clinical algorithm (Maastro), which is based on patient characteristics,
      including: age, performance status, smoking history, lung function, tumour
      staging and concomitant chemotherapy, to predict survival and toxicity outcomes.
      Potential therapeutic gains were investigated by applying isotoxic dose
      escalation to both plans using constraints for mean lung dose (18 Gy),
      oesophageal maximum (70 Gy) and spinal cord maximum (48 Gy). RESULTS: 4DCT based
      plans had lower PTV volumes, a lower dose to organs at risk and lower predicted
      NTCP rates on LKB modelling (P < 0.006). The clinical algorithm showed no
      difference for predicted 2-year survival and dyspnoea rates between the groups,
      but did predict for lower oesophageal toxicity with 4DCT plans (P = 0.001). There
      was no correlation between LKB modelling and the clinical algorithm for lung
      toxicity or survival. Dose escalation was possible in 15/20 cases, with a mean
      increase in dose by a factor of 1.19 (10.45 Gy) using 4DCT compared with 3DCT
      plans. CONCLUSIONS: 4DCT can theoretically improve therapeutic ratio and dose
      escalation based on dosimetric parameters and mathematical modelling. However,
      when individual characteristics are incorporated, this gain may be less evident
      in terms of survival and dyspnoea rates. 4DCT allows potential for isotoxic dose
      escalation, which may lead to improved local control and better overall survival.

PMID- 24332211
TI  - Midwives' beliefs and concerns about telephone conversations with women in early
      labour.
AB  - OBJECTIVE: to explore midwives' concerns, experiences and perceptions of the
      purpose of telephone contacts with women in early labour. DESIGN: a qualitative
      design based on interpretive phenomenology. SETTING: two Maternity Units in the
      Midlands of England. PARTICIPANTS: three focus groups of labour ward midwife
      coordinators and labour ward midwives and nine in-depth interviews of midwives,
      obstetricians and labour ward receptionists. FINDINGS: the principal finding was
      that midwives are trying to reconcile gatekeeping of labour wards with individual
      support for women and these two aspects are often in conflict. Women experiencing
      prolonged or painful early labour often expect to be admitted to labour wards
      whereas midwives operate from a belief that women should only be accepted onto
      labour ward in active labour. They hold this view because labour wards are busy
      places and being admitted early contributes to unnecessary medical intervention.
      KEY CONCLUSIONS: because midwives are trying to reconcile the two conflicting
      priorities of responding to women's needs and protecting the labour ward from
      inappropriate admissions, the potential always exists for women's needs to be
      'not heard' or marginalised. IMPLICATIONS FOR PRACTICE: the primary
      recommendation is that early labour telephone triage should be a discrete
      service, staffed by midwives who have been trained for this service, working
      independently of labour ward workloads.

PMID- 24332212
TI  - Rehabilitation activities, out-patient visits and employment in patients and
      partners the first year after ICU: a descriptive study.
AB  - OBJECTIVES: To describe the influence of critical illness on patients and their
      partners in relation to rehabilitation, healthcare consumption and employment
      during the first year after Intensive Care Unit discharge. DESIGN: Longitudinal,
      observational and descriptive. SETTING: Five Danish Intensive Care Units.
      METHODS: Data were collected from hospital charts, population registers and
      interviews with 18 patients and their partners at 3 and 12 months after intensive
      care discharge. Descriptive statistical analysis was performed. RESULTS: Post
      discharge inpatient rehabilitation was median (range) 52 (15-174) days (n=10).
      Community-based training was 12 (3-34) weeks (n=15). Neuropsychological
      rehabilitation following brain damage was 13-20 weeks (n=3). Number of out
      patient visits 1 year before and 1 year after were mean 3 versus 8, and General
      Practitioner visits were 12 versus 18. Three patients resumed work at pre
      hospitalisation employment rates after 12 months. After the patients' stay in
      intensive care, partners' mean full-time sick leave was 17 (range 0-124) days and
      21 (range 0-106) days part time. Partners often had long commutes. CONCLUSION:
      Most patients had comprehensive recovery needs requiring months of
      rehabilitation. Some partners needed extensive sick leave. The study reveals the
      human cost of critical illness and intensive care for patients and partners in
      the Danish welfare system.

PMID- 24332213
TI  - (+)-Pisatin biosynthesis: from (-) enantiomeric intermediates via an achiral 7,2'
      dihydroxy-4',5'-methylenedioxyisoflav-3-ene.
AB  - (+)-Pisatin, produced by peas (Pisum sativum L.), is an isoflavonoid derivative
      belonging to the pterocarpan family. It was the first chemically identified
      phytoalexin, and subsequent research has demonstrated that most legumes produce
      pterocarpans with the opposite stereochemistry. Studies on the biosynthesis of
      (+)-pisatin have shown that (-) enantiomeric compounds are intermediates in (+)
      pisatin synthesis. However, the steps from the (-)-7,2'-dihydroxy-4',5'
      methylenedioxyisoflavanone [(-)-sophorol] intermediate to (+)-6a-hydroxymaackiain
      intermediate are undetermined. Chemical reduction of (-)-sophorol using sodium
      borohydride (NaBH4) produced two isomers of (-)-7,2'-dihydroxy-4',5'
      methylenedioxyisoflavanol [(-)-DMDI] with optimal UV absorbance at 299.3 and
      300.5 nm, respectively. In contrast, enzymatic reduction of (-)-sophorol by the
      pea enzyme sophorol reductase (SOR) produced only the 299.3 nm (-)-DMDI isomer.
      Proton nuclear magnetic resonance ((1)H NMR) analysis of the 299.3 nm (-)-DMDI
      isomer demonstrated that this isomer had the same NMR spectrum as previously
      reported for cis-isoflavanol isomers, indicating that cis-(-)-DMDI is an
      intermediate in (+)-pisatin biosynthesis. Enzyme assays using protein extracts
      from pea tissue treated with CuCl2 as an elicitor converted the cis-(-)-DMDI
      isomer into an achiral isoflavene, 7,2'-dihydroxy-4',5'-methylenedioxyisoflav-3
      ene (DMDIF), and the trans-(-)-DMDI isomer was not metabolized by the same
      protein preparation. A comparison of the enzyme activities on cis-(-)-DMDI with
      protein preparations from elicited tissue versus non-elicited tissue showed a
      threefold increase in the amount of activity in the proteins from the elicited
      tissue. Proteins from the elicited tissues of alfalfa, bean, and chickpea
      converted cis-(-)-DMDI into either (-)-maackiain and/or (-)-sophorol, while
      proteins from the elicited tissues of broccoli and pepper produced no detectable
      product. These results are consistent with the involvement of cis-(-)-DMDI and
      the achiral DMDIF as intermediates in (+)-pisatin biosynthesis.

PMID- 24332214
TI  - Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid
      leukemia in accelerated phase.
AB  - BACKGROUND: Accelerated phase CML most frequently represents a progression state
      in CML. However, some patients present with AP features at the time of diagnosis.
      There is limited information on the outcome of these patients who received TKIs
      as initial therapy. PATIENTS AND METHODS: We analyzed the outcome of 51
      consecutive patients with CML who presented with features of AP at the time of
      diagnosis, including blasts >= 15% (n = 6), basophils >= 20% (n = 22), platelets
      < 100 * 10(9)/L (n = 3), cytogenetic clonal evolution (n = 17), or more than 1
      feature (n = 3). Patients received initial therapy with imatinib (n = 30),
      dasatinib (n = 5), or nilotinib (n = 16). RESULTS: The rate of complete
      cytogenetic response for patients treated with imatinib was 80%, and with
      dasatinib or nilotinib was 90%. Major molecular response (MMR) (Breakpoint
      Cluster Region (BCR)-Abelson (ABL)/ABL <= 0.1%, International Scale [IS]) was
      achieved in 69% of patients including complete molecular response (BCR-ABL/ABL <=
      0.0032% IS) in 49%. MMR rates for patients treated with imatinib were 63%, and
      with 2GTKIs, 76%. Overall survival at 36 months was 87% with imatinib and 95%
      with 2GTKIs. CONCLUSION: TKIs should be considered standard initial therapy for
      patients with AP at the time of diagnosis.

PMID- 24332215
TI  - Ribosomal S6 kinase and AKT phosphorylation as pharmacodynamic biomarkers in
      patients with myelodysplastic syndrome treated with RAD001.
AB  - BACKGROUND: Myelodysplastic syndrome (MDS) continues to cause major morbidity and
      mortality; thus, novel treatments are needed. The mammalian target of rapamycin
      (mTOR) inhibitor RAD001 (everolimus) inhibits cellular pathways important to MYC
      protein stability and cell growth. Pharmacodynamic biomarkers could be useful in
      distinguishing between (1) disease resistance that occurs even though mTOR is
      successfully inhibited (suggesting a need for a different treatment strategy) and
      (2) resistance that might respond to changes in drug dosage or schedule. PATIENTS
      AND METHODS: This was a small phase II trial of RAD001 in patients with low- and
      intermediate-1-risk MDS (n = 7). Protein S6K1 (S6) is downstream of mTOR, whereas
      protein kinase B (AKT) is upstream of mTOR. Therefore, to evaluate the
      pharmacodynamic effects of RAD001, S6 and AKT phosphorylation (pS6, pAKT) were
      measured by peripheral blood flow cytometry. RESULTS: Sequential weeks of RAD001
      produced a decrease in pS6, whereas pAKT was maintained or increased. There were
      no clinical responses despite the biomarker evidence of intended pharmacodynamic
      effect. CONCLUSION: The pS6:pAKT ratio could be useful as a biomarker of target
      inhibition by RAD001 (clinicaltrials.gov identifier: NCT00809185).

PMID- 24332216
TI  - Sputum neutrophil counts are associated with more severe asthma phenotypes using
      cluster analysis.
AB  - BACKGROUND: Clinical cluster analysis from the Severe Asthma Research Program
      (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of
      early-onset allergic asthma, late-onset severe asthma, and severe asthma with
      chronic obstructive pulmonary disease characteristics. Analysis of induced sputum
      from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns.
      Subjects with concurrent increases in eosinophil (>=2%) and neutrophil (>=40%)
      percentages had characteristics of very severe asthma. OBJECTIVE: To better
      understand interactions between inflammation and clinical subphenotypes, we
      integrated inflammatory cellular measures and clinical variables in a new cluster
      analysis. METHODS: Participants in SARP who underwent sputum induction at 3
      clinical sites were included in this analysis (n = 423). Fifteen variables,
      including clinical characteristics and blood and sputum inflammatory cell
      assessments, were selected using factor analysis for unsupervised cluster
      analysis. RESULTS: Four phenotypic clusters were identified. Cluster A (n = 132)
      and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with
      paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast,
      these inflammatory patterns were present in only 7% of cluster C (n = 117) and D
      (n = 47) subjects who had moderate-to-severe asthma with frequent health care use
      despite treatment with high doses of inhaled or oral corticosteroids and, in
      cluster D, reduced lung function. The majority of these subjects (>83%) had
      sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline
      lung function and sputum neutrophil percentages were the most important variables
      determining cluster assignment. CONCLUSION: This multivariate approach identified
      4 asthma subphenotypes representing the severity spectrum from mild-to-moderate
      allergic asthma with minimal or eosinophil-predominant sputum inflammation to
      moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic
      inflammation.

PMID- 24332217
TI  - Impact of Down syndrome on the performance of neonatal screening assays for
      severe primary immunodeficiency diseases.

PMID- 24332218
TI  - Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells
      antagonist BI 671800 in patients with seasonal allergic rhinitis.
AB  - BACKGROUND: The inflammatory response in patients with seasonal allergic rhinitis
      (SAR) is partly mediated by the prostaglandin D2 receptor chemoattractant
      receptor homologous molecule on T(H)2 cells (CRTH2). OBJECTIVE: We sought to
      investigate the efficacy and safety of the oral CRTH2 antagonist BI 671800 (50,
      200, and 400 mg twice daily), fluticasone propionate nasal spray (200 MUg once
      daily), or oral montelukast (10 mg once daily) administered for 2 weeks in
      patients with SAR. METHODS: In this randomized, double-blind, placebo-controlled,
      partial-crossover study, participants aged 18 to 65 years with a positive skin
      prick test to Dactylis glomerata pollen were exposed to out-of-season allergen in
      the environmental challenge chamber for 6 hours. The primary efficacy variable
      was the total nasal symptom score assessed as the area under the curve (AUC)(0
      6h). RESULTS: In total, 146 patients (63.7% male; mean age, 36.1 years) were
      randomized. The adjusted mean total nasal symptom score AUC(0-6h) was
      significantly reduced versus placebo with 200 mg of BI 671800 (absolute
      difference, -0.85; percentage difference, -17%; P = .0026), montelukast (absolute
      difference, -0.74; percentage difference, -15%; P = .0115), and fluticasone
      propionate (absolute difference, -1.64; percentage difference, -33%; P < .0001).
      Compared with placebo, BI 671800 significantly reduced nasal eosinophil values (P
      < .05 for all doses), significantly inhibited nasal inflammatory cytokine levels
      (IL-4 and eotaxin, P < .05; 200 mg twice daily), and induced a dose-related
      reduction in ex vivo prostaglandin D2-mediated eosinophil shape change.
      CONCLUSION: Two hundred milligrams of BI 671800 twice daily demonstrated efficacy
      in treating SAR symptoms induced by environmental challenge chamber allergen
      exposure and had a favorable safety profile.

PMID- 24332219
TI  - Recombination-activating gene 1 (Rag1)-deficient mice with severe combined
      immunodeficiency treated with lentiviral gene therapy demonstrate autoimmune
      Omenn-like syndrome.
AB  - BACKGROUND: Recombination-activating gene 1 (RAG1) deficiency results in severe
      combined immunodeficiency (SCID) caused by a complete lack of T and B
      lymphocytes. If untreated, patients succumb to recurrent infections. OBJECTIVES:
      We sought to develop lentiviral gene therapy for RAG1-induced SCID and to test
      its safety. METHODS: Constructs containing the viral spleen-focus-forming virus
      (SF), ubiquitous promoters, or cell type-restricted promoters driving sequence
      optimized RAG1 were compared for efficacy and safety in sublethally
      preconditioned Rag1(-/-) mice undergoing transplantation with transduced bone
      marrow progenitors. RESULTS: Peripheral blood CD3(+) T-cell reconstitution was
      achieved with SF, ubiquitous promoters, and cell type-restricted promoters but 3-
      to 18-fold lower than that seen in wild-type mice, and with a compromised
      CD4(+)/CD8(+) ratio. Mitogen-mediated T-cell responses and T cell-dependent and T
      cell-independent B-cell responses were not restored, and T-cell receptor patterns
      were skewed. Reconstitution of mature peripheral blood B cells was approximately
      20-fold less for the SF vector than in wild-type mice and often not detectable
      with the other promoters, and plasma immunoglobulin levels were abnormal. Two
      months after transplantation, gene therapy-treated mice had rashes with cellular
      tissue infiltrates, activated peripheral blood CD44(+)CD69(+) T cells, high
      plasma IgE levels, antibodies against double-stranded DNA, and increased B cell
      activating factor levels. Only rather high SF vector copy numbers could boost T-
      and B-cell reconstitution, but mRNA expression levels during T- and B-cell
      progenitor stages consistently remained less than wild-type levels. CONCLUSIONS:
      These results underline that further development is required for improved
      expression to successfully treat patients with RAG1-induced SCID while
      maintaining low vector copy numbers and minimizing potential risks, including
      autoimmune reactions resembling Omenn syndrome.

PMID- 24332220
TI  - Penicillin allergy as a public health measure.

PMID- 24332221
TI  - Infantile eczema: Prognosis and risk of asthma and rhinitis in preadolescence.

PMID- 24332222
TI  - Characterization of factors associated with systemic corticosteroid use in severe
      asthma: data from the Severe Asthma Research Program.

PMID- 24332223
TI  - Fractionated stereotactic radiotherapy using CyberKnife for the treatment of
      large brain metastases: a dose escalation study.
AB  - AIMS: To evaluate the toxicity and efficacy of fractionated stereotactic
      radiotherapy (FSRT) with doses of 18-30 Gy in three fractions and 21-35 Gy in
      five fractions against large brain metastases. MATERIALS AND METHODS: Between
      2005 and 2012, 61 large brain metastases (>= 2.5 cm in maximum diameter) of a
      total of 102 in 54 patients were treated with FSRT as a first-line therapy.
      Neurological symptoms were observed in 47 of the 54 patients before FSRT. Three
      fractions were applied to tumours with a maximum diameter >= 2.5 cm and <4 cm,
      and five fractions were used for brain metastases >= 4 cm. After ensuring that
      the toxicities were acceptable (<= grade 2), doses were escalated in steps. Doses
      to the large brain metastases were as follows: level I, 18-22 Gy/three fractions
      or 21-25 Gy/five fractions; level II, 22-27 Gy/three fractions or 25-31 Gy/five
      fractions; level III, 27-30 Gy/three fractions or 31-35 Gy/five fractions. Level
      III was the target dose level. RESULTS: Overall survival rates were 52 and 31% at
      6 and 12 months, respectively. Local tumour control rates of the 102 total brain
      metastases were 84 and 78% at 6 and 12 months, respectively. Local tumour control
      rates of the 61 large brain metastases were 77 and 69% at 6 and 12 months,
      respectively. Grade 3 or higher toxicities were not observed. CONCLUSIONS: The
      highest dose levels of 27-30 Gy/three fractions and 31-35 Gy/five fractions
      seemed to be tolerable and effective in controlling large brain metastases. These
      doses can be used in future studies on FSRT for large brain metastases.

PMID- 24332224
TI  - Clinical and mutational spectra of 23 Chinese patients with glutaric aciduria
      type 1.
AB  - OBJECTIVE: Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder
      caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. In
      this study, the clinical presentation and molecular aspects of 23 Chinese
      patients (11 males and 12 females) were investigated. METHODS: All patients were
      diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Protein
      restricted diet supplemented with special formula, l-carnitine and GABA analog
      were initialed after diagnosis. The clinical and biochemical features were
      analyzed. Mutational analysis of GCDH was conducted. RESULTS: Clinical
      manifestations of 23 patients varied from asymptomatic to severe encephalopathy,
      with notable phenotypic differences between siblings with the same mutations. One
      case was detected by newborn screening, while 22 Cases were diagnosed between the
      ages of 5 months and 51 years. 29 mutations in GCDH were identified. Among them,
      11 were novel, including seven missense mutations (c.406G > T, C.416C > G, c.442G
      > A, c.640A > G, c.901G > A, c.979G > A, and c.1207C > T), three frameshift
      mutations (c.873delC, c.1172-1173insT and c.1282-1285ins71) and one nonsense
      mutation (c.411C > G). In exon 5, c.553G > A and c.148T > C were found in four
      alleles (8.7%) and three alleles (6.5%) of the patients, respectively.
      CONCLUSIONS: In 23 Chinese patients with GA1, 11 novel GCDH mutations were
      identified. This may indicate that the genetic profiles of Chinese patients are
      different from those of other populations. SYNOPSIS: 23 Chinese GA1 patients with
      varied clinical manifestations have been reported. 11 novel mutations in their
      GCDH gene were identified, indicating that the genetic profiles of Chinese GA1
      patients differ from those of other populations.

PMID- 24332225
TI  - Root exudates: the hidden part of plant defense.
AB  - The significance of root exudates as belowground defense substances has long been
      underestimated, presumably due to being buried out of sight. Nevertheless, this
      chapter of root biology has been progressively addressed within the past decade
      through the characterization of novel constitutively secreted and inducible
      phytochemicals that directly repel, inhibit, or kill pathogenic microorganisms in
      the rhizosphere. In addition, the complex transport machinery involved in their
      export has been considerably unraveled. It has become evident that the profile of
      defense root exudates is not only diverse in its composition, but also strikingly
      dynamic. In this review, we discuss current knowledge of the nature and
      regulation of root-secreted defense compounds and the role of transport proteins
      in modulating their release. 

PMID- 24332226
TI  - Botanical insecticide research: many publications, limited useful data.
AB  - Our analysis of >20000 papers on botanical insecticides from 1980 to 2012,
      indicates major growth in the number of papers published annually (61 in 1980 to
      1207 in 2012), and their proportion among all papers on insecticides (1.43% in
      1980 to 21.38% in 2012). However, only one-third of 197 random articles among the
      1086 papers on botanical insecticides published in 2011 included any chemical
      data or characterization; and only a quarter of them included positive controls.
      Therefore, a substantial portion of recently published studies has design flaws
      that limit reproducibility and comparisons with other and/or future studies. In
      our opinion, much of the scientific literature on this subject is of limited use
      in the progress toward commercialization or advancement of knowledge, given the
      resources expended. 

PMID- 24332227
TI  - Why measure enzyme activities in the era of systems biology?
AB  - Information about the abundance and biological activities of proteins is
      essential to reveal how genes affect phenotypes. Over the past decade, mass
      spectrometry (MS)-based proteomics has revolutionized the identification and
      quantification of proteins, and the detection of post-translational
      modifications. Interpretation of proteomics data depends on information about the
      biological activities of proteins, which has created a bottleneck in research.
      This review focuses on enzymes in central metabolism. We examine the methods used
      for measuring enzyme activities, and discuss how these methods provide
      information about the kinetic and regulatory properties of enzymes, their
      turnover, and how this information can be integrated into metabolic models. We
      also discuss how robotized assays could enable the genetic networks that control
      enzyme abundance to be analyzed. 

PMID- 24332228
TI  - Dr. Rene Cailliet: Advancing the field of musculoskeletal medicine by making the
      complicated understandable.

PMID- 24332230
TI  - Patient satisfaction surveys: tools to enhance patient care or flawed outcome
      measures?

PMID- 24332229
TI  - Physical activity, exercise, and health-related measures of fitness in adults
      with spina bifida: a review of the literature.
AB  - Spina bifida (SB) is the most common birth defect in United States that results
      in permanent lifelong disability according to the Spina Bifida Association.
      Advancements in medical care have led to a longer life span and an increase in
      the risk of secondary conditions, for example, obesity, with age. The need to
      maintain a healthy and active lifestyle is even stronger in adults with SB than
      the general population. Our objective was to fill a gap in the literature by
      highlighting the current state of the literature on health-related measures of
      fitness, exercise, and physical activity (PA) in adults with SB. PubMed and Ovid
      were searched for articles by using the terms "spina bifida or myelomeningocele
      and exercise," published between January 1, 1988 and May 10, 2012. Results of
      studies showed that adults with SB had an inactive lifestyle, lower aerobic
      capacity, decreased level of daily PA, higher prevalence of obesity, and lower
      health-related quality of life compared with reference groups. Therapeutic
      interventions reduced pain, increased biomechanical efficiency during wheelchair
      propulsion, and improved PA and balance. Overall, the quality of the evidence on
      PA, exercise, and health-related measures of fitness is low in SB. Given
      misdistribution of adipose tissue, short stature, scoliosis, and joint
      contractures, future research should be conducted to determine the most reliable
      and low-cost methods of measuring body composition and to establish norms. Other
      reference standards, for example, aerobic capacity, require further development.
      Studies are needed to investigate lifestyle interventions that facilitate PA and
      exercise, and to determine the amount of exercise required to reduce secondary
      conditions as people with SB age.

PMID- 24332231
TI  - Deleterious cognitive and motoric effects of haloperidol in an adolescent with
      cerebral palsy: a case report.
AB  - This case report describes a 15-year-old male patient with spastic diplegic
      cerebral palsy, Gross Motor Function Classification System Level III, who
      developed severe new cognitive and motoric impairments after the administration
      of haloperidol. He received this dopamine antagonist and typical antipsychotic
      medication for an acute postoperative episode of agitation. He improved when he
      received the dopamine agonists amantadine and carbidopa/levodopa. This case
      suggests that dopamine blockade may be deleterious for individuals with cerebral
      palsy. Potential explanations for the events observed in this case are also
      presented.

PMID- 24332232
TI  - Referral to physical therapy of a previously undiagnosed ankle metastatic lesion.

PMID- 24332233
TI  - Conscientious objection to the provision of reproductive healthcare.

PMID- 24332234
TI  - Conscientious objection and refusal to provide reproductive healthcare: a White
      Paper examining prevalence, health consequences, and policy responses.
AB  - BACKGROUND: Global Doctors for Choice-a transnational network of physician
      advocates for reproductive health and rights-began exploring the phenomenon of
      conscience-based refusal of reproductive healthcare as a result of increasing
      reports of harms worldwide. The present White Paper examines the prevalence and
      impact of such refusal and reviews policy efforts to balance individual
      conscience, autonomy in reproductive decision making, safeguards for health, and
      professional medical integrity. OBJECTIVES AND SEARCH STRATEGY: The White Paper
      draws on medical, public health, legal, ethical, and social science literature
      published between 1998 and 2013 in English, French, German, Italian, Portuguese,
      and Spanish. Estimates of prevalence are difficult to obtain, as there is no
      consensus about criteria for refuser status and no standardized definition of the
      practice, and the studies have sampling and other methodologic limitations. The
      White Paper reviews these data and offers logical frameworks to represent the
      possible health and health system consequences of conscience-based refusal to
      provide abortion; assisted reproductive technologies; contraception; treatment in
      cases of maternal health risk and inevitable pregnancy loss; and prenatal
      diagnosis. It concludes by categorizing legal, regulatory, and other policy
      responses to the practice. CONCLUSIONS: Empirical evidence is essential for
      varied political actors as they respond with policies or regulations to the
      competing concerns at stake. Further research and training in diverse
      geopolitical settings are required. With dual commitments toward their own
      conscience and their obligations to patients' health and rights, providers and
      professional medical/public health societies must lead attempts to respond to
      conscience-based refusal and to safeguard reproductive health, medical integrity,
      and women's lives.

PMID- 24332235
TI  - Conscientious objection or fear of social stigma and unawareness of ethical
      obligations.
AB  - Conscientious objection is a legitimate right of physicians to reject the
      practice of actions that violate their ethical or moral principles. The
      application of that principle is being used in many countries as a justification
      to deny safe abortion care to women who have the legal right to have access to
      safe termination of pregnancy. The problem is that, often, this concept is abused
      by physicians who camouflage under the guise of conscientious objection their
      fear of experiencing discrimination and social stigma if they perform legal
      abortions. These colleagues seem to ignore the ethical principle that the primary
      conscientious duty of OB/GYNs is-at all times-to treat, or provide benefit and
      prevent harm to, the patients for whose care they are responsible. Any
      conscientious objection to treating a patient is secondary to this primary duty.
      One of the jobs of the FIGO Working Group for the Prevention of Unsafe Abortion
      is to change this paradigm and make our colleagues proud of providing legal
      abortion services that protect women's life and health, and concerned about
      disrespecting the human rights of women and professional ethical principles. 

PMID- 24332236
TI  - Conscientious objection to provision of legal abortion care.
AB  - Despite advances in scientific evidence, technologies, and human rights rationale
      for providing safe abortion, a broad range of cultural, regulatory, and health
      system barriers that deter access to abortion continues to exist in many
      countries. When conscientious objection to provision of abortion becomes one of
      these barriers, it can create risks to women's health and the enjoyment of their
      human rights. To eliminate this barrier, states should implement regulations for
      healthcare providers on how to invoke conscientious objection without
      jeopardizing women's access to safe, legal abortion services, especially with
      regard to timely referral for care and in emergency cases when referral is not
      possible. In addition, states should take all necessary measures to ensure that
      all women and adolescents have the means to prevent unintended pregnancies and to
      obtain safe abortion. 

PMID- 24332237
TI  - Legal and ethical standards for protecting women's human rights and the practice
      of conscientious objection in reproductive healthcare settings.
AB  - The practice of conscientious objection by healthcare workers is growing across
      the globe. It is most common in reproductive healthcare settings because of the
      religious or moral values placed on beliefs as to when life begins. It is often
      invoked in the context of abortion and contraceptive services, including the
      provision of information related to such services. Few states adequately regulate
      the practice, leading to denial of access to lawful reproductive healthcare
      services and violations of fundamental human rights. International ethical,
      health, and human rights standards have recently attempted to address these
      challenges by harmonizing the practice of conscientious objection with women's
      right to sexual and reproductive health services. FIGO ethical standards have had
      an important role in influencing human rights development in this area. They
      consider regulation of the unfettered use of conscientious objection essential to
      the realization of sexual and reproductive rights. Under international human
      rights law, states have a positive obligation to act in this regard. While
      ethical and human rights standards regarding this issue are growing, they do not
      yet exhaustively cover all the situations in which women's health and human
      rights are in jeopardy because of the practice. The present article sets forth
      existing ethical and human rights standards on the issue and illustrates the need
      for further development and clarity on balancing these rights and interests. 

PMID- 24332238
TI  - Docetaxel versus active symptom control for refractory oesophagogastric
      adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial.
AB  - BACKGROUND: Second-line chemotherapy for patients with oesophagogastric
      adenocarcinoma refractory to platinum and fluoropyrimidines has not shown
      benefits in health-related quality of life (HRQoL). We assessed whether the
      addition of docetaxel to active symptom control alone can improve survival and
      HRQoL for patients. METHODS: For this open-labelled, multicentre trial, we
      recruited patients aged 18 years or older from 30 UK centres. Patients were
      eligible if they had an advanced, histologically confirmed adenocarcinoma of the
      oesophagus, oesophagogastric junction, or stomach that had progressed on or
      within 6 months of treatment with a platinum-fluoropyrimidine combination.
      Patients could have an Eastern Cooperative Oncology Group performance status of 0
      2. We randomly assigned patients using a central, computerised minimisation
      procedure to receive docetaxel plus active symptom control, or active symptom
      control alone (1:1; stratified by disease status, disease site, duration of
      response to previous chemotherapy, and performance status). Docetaxel was given
      at a dose of 75 mg/m(2) by intravenous infusion every 3 weeks for up to six
      cycles. The primary endpoint was overall survival, analysed by intention to
      treat. This is the report of the planned final analysis. This study is an
      International Standardised Randomised Controlled Trial, number ISRCTN13366390.
      FINDINGS: Between April 21, 2008, and April 26, 2012, we recruited 168 patients,
      allocating 84 to each treatment group. After a median follow-up of 12 months [IQR
      10-21]) and 161 (96%) deaths (80 in the docetaxel group, 81 in the active symptom
      control group), median overall survival in the docetaxel group was 5.2 months
      (95% CI 4.1-5.9) versus 3.6 months (3.3-4.4) in the active symptom control group
      (hazard ratio 0.67, 95% CI 0.49-0.92; p=0.01). Docetaxel was associated with
      higher incidence of grade 3-4 neutropenia (12 [15%] patients vs no patients),
      infection (15 [19%] patients vs two [3%] patients), and febrile neutropenia (six
      [7%] patients vs no patients). Patients receiving docetaxel reported less pain
      (p=0.0008) and less nausea and vomiting (p=0.02) and constipation (p=0.02).
      Global HRQoL was similar between the groups (p=0.53). Disease specific HRQoL
      measures also showed benefits for docetaxel in reducing dysphagia (p=0.02) and
      abdominal pain (p=0.01). INTERPRETATION: Our findings suggest that docetaxel can
      be recommended as an appropriate second-line treatment for patients with
      oesophagogastric adenocarcinoma that is refractory to treatment with platinum and
      fluoropyrimidine. FUNDING: Cancer Research UK.

PMID- 24332239
TI  - Second-line chemotherapy for patients with oesophagogastric adenocarcinoma.

PMID- 24332240
TI  - A new era of treatment for chronic lymphocytic leukaemia?

PMID- 24332242
TI  - Reduction of operator radiation dose by an extended lower body shield.
AB  - PURPOSE: To quantify the reduction in operator exposure to scatter radiation by
      using an extension component in addition to a commonly used lower body radiation
      shield attached to an interventional radiology procedure table. MATERIALS AND
      METHODS: An anthropomorphic pelvis phantom was exposed to fluoroscopy at varying
      C-arm angles to simulate a standard interventional procedure. A MAVIG UT60 lower
      body shield (MAVIG, Munich, Germany) (48 cm * 78 cm, 0.5 mm lead equivalent),
      with an attachable extension component (48 cm * 36 cm), was suspended from the
      edge of the table adjacent to the pelvic phantom. Using a handheld Geiger
      counter, scatter radiation exposure rates were measured at the level of an
      operator's eye, chest, waist, and knee, with various C-arm angles both with and
      without the attachable extension component. Mean exposure rates for each
      experimental setup were calculated and compared. RESULTS: Overall, scatter
      radiation exposures were lower with the addition of the extension component, with
      the largest reductions (> 80%) measured at the operator's waist and knee levels,
      for all C-arm angles. The highest reduction in scatter radiation exposure was
      measured at knee level, at 0 degrees left posterior oblique projection, where the
      use of the lower body shield extension component reduced the exposure rate from
      4.80 mR/h to 0.44 mR/h (90.8% reduction, P < .001). Reductions in scatter
      radiation were less at eye and chest levels. CONCLUSIONS: The use of the
      additional extension component to the lower body radiation shield can result in
      large (> 80%) reductions in operator scatter radiation exposure, particularly to
      the lower body.

PMID- 24332241
TI  - Ibrutinib as initial therapy for elderly patients with chronic lymphocytic
      leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2
      trial.
AB  - BACKGROUND: Chemoimmunotherapy has led to improved numbers of patients achieving
      disease response, and longer overall survival in young patients with chronic
      lymphocytic leukaemia; however, its application in elderly patients has been
      restricted by substantial myelosuppression and infection. We aimed to assess
      safety and activity of ibrutinib, an orally administered covalent inhibitor of
      Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older
      with chronic lymphocytic leukaemia. METHODS: In our open-label phase 1b/2 trial,
      we enrolled previously untreated patients at clinical sites in the USA. Eligible
      patients were aged at least 65 years, and had symptomatic chronic lymphocytic
      leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28
      day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose
      was discontinued after enrolment had begun because comparable activity of the
      doses has been shown. The primary endpoint was the safety of the dose-fixed
      regimen in terms of frequency and severity of adverse events for all patients who
      received treatment. This study is registered with ClinicalTrials.gov, number
      NCT01105247. FINDINGS: Between May 20, 2010, and Dec 18, 2012, we enrolled 29
      patients with chronic lymphocytic leukaemia and two patients with small
      lymphocytic lymphoma. Median age was 71 years (range 65-84), and 23 (74%)
      patients were at least 70 years old. Toxicity was mainly of mild-to-moderate
      severity (grade 1-2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%]
      patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients).
      15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in
      three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five
      [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient).
      Three (10%) patients developed grade 3 infections, although no grade 4 or 5
      infections occurred. One patient developed grade 3 neutropenia, and one developed
      grade 4 thrombocytopenia. After a median follow-up of 22.1 months (IQR 18.4
      23.2), 22 (71%) of 31 patients achieved an objective response (95% CI 52.0-85.8);
      four patients (13%) had a complete response, one patient (3%) had a nodular
      partial response, and 17 (55%) patients had a partial response. INTERPRETATION:
      The safety and activity of ibrutinib in elderly, previously untreated patients
      with symptomatic chronic lymphocytic leukaemia, or small lymphocytic lymphoma is
      encouraging, and merits further investigation in phase 3 trials. FUNDING:
      Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and
      Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD.

PMID- 24332243
TI  - Outpatient single-session yttrium-90 glass microsphere radioembolization.
AB  - PURPOSE: To investigate the feasibility of yttrium-90 ((90)Y) glass microsphere
      radioembolization (including angiography, lung shunt assessment, and treatment)
      as a single-session, outpatient procedure. MATERIALS AND METHODS: Between January
      2008 and June 2013, 14 patients underwent outpatient, single-session
      radioembolization with (90)Y glass microspheres. As part of the routine
      diagnostic work-up, all patients underwent either computed tomography (CT) or
      magnetic resonance imaging of the liver with three-dimensional analysis and had
      laboratory results forwarded to our center for confirmation of candidacy before
      treatment. On treatment day, all patients underwent planning mesenteric
      angiography with flat panel cone-beam CT imaging. Patients were administered 33
      85 MBq of technetium-99m macroaggregated albumin ((99m)Tc-MAA) via a
      microcatheter positioned in a hepatic artery supplying the tumor of interest.
      Planar scintigraphy was initiated within 2 hours after the administration of
      (99m)Tc-MAA and lung shunt fraction was determined. Final dosimetry calculations
      were performed while the patient was being transferred back from nuclear medicine
      to interventional radiology. RESULTS: All patients successfully underwent
      planning angiography with administration of (99m)Tc-MAA and (90)Y
      radioembolization as a single-session treatment. There were no reportable or
      recordable medical events; treatment was carried out to the desired dose in all
      cases. The mean total procedure time was 2.70 hours +/- 0.72 (range, 1.63-3.97
      h). CONCLUSIONS: This study reports a novel proof of concept for performing
      radioembolization in a single-session setting. By using the described method,
      time between initial clinical assessments and radioembolization treatment is
      decreased, and costs are minimized.

PMID- 24332244
TI  - Prescribing practices for intravenous aminoglycosides in UK cystic fibrosis
      clinics: a questionnaire survey.
AB  - BACKGROUND: Intravenous aminoglycoside antibiotics are widely used to treat
      pulmonary infection with Pseudomonas aeruginosa in individuals with cystic
      fibrosis (CF). Over the last decade evidence has accumulated showing that the
      choice of aminoglycoside and the dosing regimen may help reduce adverse effects
      such as nephrotoxicity. METHODS: We undertook an online survey to determine
      current practice in UK CF Centres. RESULTS: We received a response from 35/48
      (73%) centres. A once daily regimen was used in 30/35 (86%) centres. Around one
      third had stopped using gentamicin in the last 10 years. In most cases
      respondents reported changing practice in response to new evidence or evidence
      based guidelines. Obstacles to introducing evidence based practice were
      identified both at the level of the CF Centre and the hospital trust.
      CONCLUSIONS: A once daily aminoglycoside regimen is now used in the majority of
      UK CF Centres. Tobramycin is first line and many centres have stopped using
      gentamicin. Obstacles to evidence based practice remain in a minority of centres.

PMID- 24332245
TI  - In-hospital arrhythmia development and outcomes in pediatric patients with acute
      myocarditis.
AB  - Cardiac arrhythmias are a complication of myocarditis. There are no large studies
      of in-hospital arrhythmia development and outcomes in pediatric patients with
      acute myocarditis. This was a retrospective 2-center review of patients <=21
      years hospitalized with acute myocarditis from 1996 to 2012. Fulminant
      myocarditis was defined as the need for inotropic support within 24 hours of
      presentation. Acute arrhythmias occurred at presentation and subacute after
      admission. Eighty-five patients (59% men) presented at a median age of 10 years
      (1 day to 18 years). Arrhythmias occurred in 38 patients (45%): 16 acute, 12
      subacute, and 9 acute and subacute (1 onset unknown). Arrhythmias were associated
      with low voltages on the electrocardiogram (14 of 34, 41% vs 6 of 47, 13%; odds
      ratio [OR] 4.78, 95% confidence interval [CI] 1.60 to 14.31) and worse outcome
      (mechanical support, orthotopic heart transplant, or death; OR 7.59, 95% CI 2.61
      to 22.07) but were not statistically significantly associated with a fulminant
      course, ST changes, initial myocardial function, lactate, creatinine level, C
      reactive protein and/or erythrocyte sedimentation rate, or troponin I level,
      after adjusting for multiple comparisons. Subacute arrhythmias were associated
      with preceding ST changes (10 of 15, 67% vs 15 of 59, 25%, OR 5.87, 95% CI 1.73
      to 19.93). All patients surviving to discharge had arrhythmia resolution or
      control before discharge (10 on antiarrhythmic), with 1 exception (patient with
      complete heart block requiring a pacemaker). At 1-year follow-up, there were 3
      recurrences of ventricular arrhythmias, but no arrhythmia-related mortality. In
      conclusion, arrhythmias are common in pediatric patients with myocarditis,
      occurring in nearly 1/2 of all hospitalized children and are associated with a
      worse outcome. Early identification of subacute arrhythmias using
      electrocardiographic changes may help management. A majority of patients do not
      require continued postdischarge arrhythmia treatment.

PMID- 24332247
TI  - Meta-analysis comparing carvedilol versus metoprolol for the prevention of
      postoperative atrial fibrillation following coronary artery bypass grafting.
AB  - A systematic review and meta-analysis was performed to evaluate the effects of
      carvedilol versus metoprolol on the incidence of postoperative atrial
      fibrillation in patients undergoing coronary artery bypass grafting in randomized
      controlled trials. Ovid MEDLINE, PubMed, CENTRAL, and Excepta Medica (EMBASE)
      were searched up to March 2013 for suitable randomized controlled trials. Data
      were pooled using random-effects model for pairwise analyses. A total of 4 trials
      with 601 patients were included in this analysis. Pairwise analyses showed that
      compared with metoprolol, carvedilol significantly reduced the incidence of
      postoperative atrial fibrillation (odds ratio 0.50, 95% confidence interval 0.32
      to 0.80). In conclusion, compared with metoprolol, carvedilol significantly
      reduces the incidence of postoperative atrial fibrillation in patients undergoing
      coronary artery bypass grafting. 

PMID- 24332246
TI  - Impact of the stent length on long-term clinical outcomes following newer
      generation drug-eluting stent implantation.
AB  - Stent length has been considered an important predictor of adverse events after
      percutaneous coronary intervention, even with the first-generation drug-eluting
      stents (DESs). The introduction of newer-generation DES has further reduced the
      rates of adverse clinical events such as restenosis, myocardial infarction, and
      stent thrombosis. The aim of this study was to compare the impact of stent length
      on the long-term clinical outcomes between first- and newer-generation DESs. The
      effects of stent length (>=32 vs <32 mm) on the clinical outcomes were evaluated
      in 8,445 patients who underwent percutaneous coronary intervention using either a
      first-generation DES (sirolimus- and paclitaxel-eluting stents, n = 6,334) or a
      newer-generation DES (everolimus- and zotarolimus-eluting stents, n = 2,111) from
      January 2004 to December 2009. The 3-year adverse outcomes (composite of all
      cause death, nonfatal myocardial infarction, target vessel revascularization, and
      stent thrombosis) were compared using the inverse probability of treatment
      weighted method according to the stent length. After adjustment for differences
      in the baseline risk factors, a stent length of >=32 mm was significantly
      associated with higher cumulative rates of target vessel revascularization and
      stent thrombosis in the patients treated with a first-generation DES (adjusted
      hazard ratio 1.875, 95% confidence interval 1.531 to 2.297, p <0.001; adjusted
      hazard ratio 2.964, 95% confidence interval 1.270 to 6.917, p = 0.012), but it
      was not associated with the clinical outcomes in patients treated with a newer
      generation DES. In conclusion, stent length might not be associated with long
      term clinical outcomes in newer-generation DES era, whereas stent length might be
      associated with long-term clinical outcomes in the first-generation DESs.

PMID- 24332248
TI  - Frequency of the use of low- versus high-dose aspirin in dual antiplatelet
      therapy after percutaneous coronary intervention (from the Dual Antiplatelet
      Therapy study).
AB  - In randomized trials, low-dose (LD) and high-dose (HD) aspirin (ASA) are equally
      effective in reducing ischemic complications, but HD ASA is associated with an
      increased risk of bleeding in the setting of dual antiplatelet therapy after
      percutaneous coronary intervention (PCI). ASA dose after PCI varies across
      countries, but little is known about variation within the United States (US) and
      whether this variation can be explained by clinical characteristics of patients.
      We used enrollment data from the Dual Antiplatelet Therapy Study, a randomized
      trial designed to compare 12 versus 30 months of dual antiplatelet therapy after
      PCI, to quantify the variation in ASA dosing after PCI in the US subjects and
      assess the extent to which dose variability was attributable to patient
      characteristics. Of the 23,336 patients enrolled in the US, 28.0% were prescribed
      LD ASA at discharge after PCI. Patient characteristics explained 1.6% of total
      variance in ASA dose, whereas the study site accounted for 45.9% of the
      unexplained variability. The median odds ratio comparing sites was 5.05 (95%
      confidence interval 4.29 to 5.85), which was greater than any individual
      predictor of ASA dose. In conclusion, LD ASA after PCI in the US was used in a
      minority of patients, and heterogeneity in its selection was mainly influenced by
      the site of enrollment rather than patient characteristics. As HD ASA may be
      associated with adverse events in the setting of dual antiplatelet therapy,
      reducing local practice variation in the dose of ASA may be a target for quality
      improvement. 

PMID- 24332249
TI  - Acute appendicitis presenting as acute diarrhea accompanying hypokalemia.
AB  - Acute appendicitis, characterized as periumbilical pain, migrating to the right
      iliac fossa, is one of the most common acute surgical conditions. It is usually
      diagnosed on the basis of clinical signs and symptoms. However, some patients may
      present atypically and are prone to be misdiagnosed. We report this first case of
      acute appendicitis who presented initially with complain of diarrhea accompanying
      hypokalemia. There have been no published data suggesting its existence in any
      parts of the world.

PMID- 24332250
TI  - What can we learn on medical preparedness from the use of chemical agents against
      civilians in Syria?

PMID- 24332251
TI  - Acute coronary syndrome and sildenafil - coincidence or coexistence: author
      reply.

PMID- 24332252
TI  - Supine chest compression: alternative to prone ventilation in acute respiratory
      distress syndrome.
AB  - Prone ventilation is usually used for severe acute respiratory distress syndrome.
      We applied an alternative method to prone position. We described 2 cases of
      trauma where prone position could not be done. Chest wall compression was
      performed by 2-kg weight in front of the chest wall bilaterally while the patient
      was in a supine position. Respiratory mechanics work to improve oxygenation
      almost as same as the mechanism proposed for prone position without any major
      adverse effects and serious complications. We suggest a larger randomized study
      to determine the efficacy and also to find out the optimum weight required to
      compress the chest.

PMID- 24332253
TI  - An urban Northeastern United States alligator bite.
AB  - Individuals who live and work in the Southeastern coastal range of the 3 US
      crocodilian carnivores, American alligators, American crocodiles, and caiman,
      understand the risks of reptile-human encounters. Individuals who live in other
      parts of the country maybe exposed through contact with exotic pets at private
      homes, small menageries, or petting zoos or from escaped or abandoned animals.
      During these encounters, individuals may be severely injured.Emergency medical
      services, law enforcement, and animal welfare workers in nonhabitat areas are
      usually not trained in the handling and safe removal of injured individuals from
      the scene when the reptile is present. The emergency management of large
      crocodilian injuries is similar to that of other major trauma; however, providers
      also must take into consideration the significant crush component potentially
      inflicted by the tremendous bite power and shaking inflicting during attacks by
      these large reptiles, appropriate antibiotic coverage for less common organisms
      that inhabit their mouths, and management of possible psychological distress,
      including posttraumatic stress disorder produced by such an unusual attack.
      Emergency physicians should support the development of a readily available
      national database of scientifically collect information on attacks to inform
      appropriate care and support efforts to explore responsible measures that the
      USDA Animal and Plant Health Inspection Service and other appropriate local,
      state, and federal agencies can take to ensure ethical and biologically
      sustainable management of our large reptiles, which also helps to ensure the
      safety of the public.

PMID- 24332254
TI  - Integrating family planning and prevention of mother to child HIV transmission in
      Zimbabwe.
AB  - OBJECTIVE: The objective was to integrate enhanced family planning (FP) and
      prevention of mother-to-child HIV transmission services in order to help HIV
      positive Zimbabwean women achieve their desired family size and spacing as well
      as to maximize maternal and child health. STUDY DESIGN: HIV-positive pregnant
      women were enrolled into a standard-of-care (SOC, n=33) or intervention (n=65)
      cohort, based on study entry date, and followed for 3 months postpartum. The
      intervention cohort received education sessions aimed at increasing FP use and
      negotiation power. Both groups received care from nurses with enhanced FP
      training. Outcomes included FP use, FP knowledge and HIV disclosure, and were
      assessed with Fisher's Exact Tests, binomial tests and t tests. RESULTS: The
      intervention cohort reported increased control over condom use (p=.002),
      increased knowledge about IUDs (p=.002), increased relationship power (p=.01) and
      increased likelihood of disclosing their HIV status to a partner (p=.04) and
      having that partner disclose to them (p=.04) when compared to the SOC cohort.
      Long-acting reversible contraception (LARC) use in both groups increased from ~2%
      at baseline to >80% at 3 months postpartum (p<.001). CONCLUSIONS: FP and sexual
      negotiation skills and knowledge, as well as HIV disclosure, increased
      significantly in the intervention cohort. LARC uptake increased significantly in
      both the intervention and SOC cohorts, likely because both groups received care
      from nurses with enhanced FP training. Successful service integration models are
      needed to maximize health outcomes in resource-constrained environments; this
      intervention is such a model that should be replicable in other settings in sub
      Saharan Africa and beyond. IMPLICATIONS: This study provides a rigorously
      evaluated intervention to integrate FP education into ante- and postnatal care
      for HIV-positive women and also to train providers on FP. Results suggest that
      this intervention had significant effects on contraception use and communication
      with sexual partners. This intervention should be adaptable to other areas.

PMID- 24332257
TI  - Cost-effectiveness of revascularization for limb preservation in patients with
      marginal functional status.
AB  - BACKGROUND: Revascularization and limb salvage attempts are often offered to
      patients with foot wounds and chronic limb ischemia who are thought to be good
      risk candidates, but some skepticism remains about the utility of these efforts
      for elderly patients with marginal functional status. We sought to determine
      whether limb preservation efforts in this population could be justified from a
      patient-centered, cost-effectiveness perspective. METHODS: A probabilistic Markov
      model was used to simulate the clinical outcomes, health utilities, and costs
      over a 10-year period with various management strategies. Clinical parameter
      estimates were obtained from previous clinical trials and large observational
      series. Cost estimates were obtained from cost literature and also a single
      center study that reviewed total costs accumulated (including secondary
      amputations, wound care, outpatient nursing care, and nursing home costs). Cost
      (in 2011 U.S. dollars) per year of ambulation (with limb preservation or with a
      prosthesis after amputation) was the primary measure of cost-effectiveness.
      RESULTS: The total 10-year costs of revascularization--either endovascular or
      surgical--were lower than the costs of either local wound care alone or primary
      amputation. Revascularization strategies also produced more health benefits as
      measured in terms of years of ambulatory ability, years of limb salvage, or
      quality-adjusted life-years. In none of the scenarios modeled in deterministic
      sensitivity analyses did primary amputation prove to be cost-effective.
      CONCLUSIONS: Revascularization and limb preservation attempts appear less costly
      and provide more health benefits than wound care alone or primary amputation,
      even among patients with marginal functional status at baseline.

PMID- 24332258
TI  - When to call it a day: incremental risk of amputation and death after multiple
      revascularization.
AB  - BACKGROUND: Patients with critical limb ischemia (CLI) often undergo
      revascularization before amputation. The exact relationship between multiple
      procedures and increased risk of amputation is unclear. We sought to determine
      the increased risk of amputation for each additional revascularization. METHODS:
      The 2007-2009 California State Inpatient Database (SID) was used to identify a
      cohort of CLI patients undergoing revascularization and conduct a time-to-event
      analysis for patients undergoing one or more revascularization procedures. One
      year estimates were generated with Kaplan-Meier curves and compared with the log
      rank test. The Wei-Lin-Weissfeld (WLW) marginal proportional hazards model was
      used to assess independent effects of number of revascularization procedures on
      amputation and death. RESULTS: A total of 11,190 patients with CLI underwent
      revascularization between July 2007 and December 2009. Their mean age was 71.0
      years (interquartile range 62-80 years) and 6255 (55.9%) were male. Over half the
      subjects (55.2%) were smokers and there was a high burden of comorbidities in the
      cohort. One-year estimates of amputation by number of revascularizations (1:
      23.3%; 2: 27.1%; 3: 30.3%; 4: 26.7%; 5(+): 28.6%; P < 0.001) and death (1: 18.7%;
      2: 21.1%; 3: 26.3%; 4: 23.6%; 5+: 32.1%; P = 0.012) increased significantly as
      procedures increased. In the WLW model for amputation, the hazard increased
      significantly for patients with 2 revascularization versus 1 (HR = 1.22; 95% CI
      1.09-1.37; P = 0.001) and 3 revascularizations versus 2 (HR = 1.33; 95% CI 1.10
      1.62; P = 0.004). In the multivariable WLW models for death, the increase in
      revascularization procedures for 2 compared with 1 (HR = 1.18; 95% CI 1.04-1.34;
      P = 0.010) was significant. CONCLUSIONS: The risk of amputation increases with
      each additional revascularization procedure. These findings hold true for both
      percutaneous transluminal angioplasty only and lower extremity bypass only
      subsets. In addition, increased revascularization procedures appear to result in
      an increased risk of death. We advocate for continued communication between
      clinicians and patients on the true risks and benefits of additional
      revascularization procedures.

PMID- 24332259
TI  - Supervised exercise program improves aerobic fitness in patients awaiting
      abdominal aortic aneurysm repair.
AB  - BACKGROUND: Aerobic fitness is an important predictor of postoperative outcome in
      major surgery. In this study, we assess the effects of a period of preoperative
      exercise on aerobic fitness as measured by cardiopulmonary exercise testing
      (CPET) in patients scheduled for abdominal aortic aneurysm (AAA) repair. METHODS:
      As part of a randomized trial, the first patients recruited in the intervention
      group were enrolled in a supervised exercise program of six week duration.
      Treadmill CPET parameters were measured before and after exercise preoperatively
      for these patients. These parameters were as follows: peak oxygen uptake (VO2
      peak), anaerobic threshold (AT), and ventilator equivalents for oxygen and carbon
      dioxide (VE/VO2 and VE/VCO2, respectively). Total exercise time and the time at
      which AT was achieved were also recorded. A comparison between pre- and
      postexercise parameters was made to detect for a possible improvement in aerobic
      fitness. RESULTS: Twenty patients with AAA (17 men; mean age: 74.9 +/- 5.9 years)
      were included in this study. Thirty-five percent of patients had a history of
      ischemic heart disease, 25% of obstructive airway disease, and 15% of cerebral
      vascular events. Seventy percent were previous smokers, and 15% were current
      smokers. Fifty-five percent of patients were taking aspirin and 75% were
      undergoing statin therapy. The median (interquartile range) VO2 peak at baseline
      was 18.2 (15.4-19.9) mL/kg/min, and after exercise was 19.9 (17.1-21.1; P =
      0.048). Median AT at baseline was 12.2 (10.5-14.9), and 14.4 (12.3-15.4) after
      exercise (P = 0.023). Time of exercise tolerated also improved from a median of
      379 to 604 sec (P = 0.001). No significant changes were seen in VE/VO2, VE/VCO2,
      or the time at which AT was achieved. CONCLUSION: This study shows that
      cardiopulmonary aerobic fitness improves after a period of supervised exercise in
      patients scheduled for AAA repair. This is justification for a randomized trial
      to assess whether this affects morbidity and mortality after AAA repair.

PMID- 24332260
TI  - Outcome predictors of limb salvage in traumatic popliteal artery injury.
AB  - BACKGROUND: Significantly reduced amputation rates for traumatic popliteal artery
      injuries have been achieved with improved revascularization and resuscitative
      techniques. Predictive scores have failed to accurately predict outcomes in
      patients who sustain popliteal artery damage. This study aimed to identify
      predictors of limb salvage in a civilian cohort after popliteal artery trauma.
      METHODS: A single-institution, retrospective review was performed of all patients
      with popliteal artery trauma presenting between January 2002 and June 2009. Data
      were compiled using the institutional trauma registry, with demographics,
      mechanism of injury, associated injury, fasciotomy, Mangled Extremity Severity
      Score (MESS), and Injury Severity Score (ISS) all documented. Statistical
      analysis included descriptive statistics, univariate analysis, and multiple exact
      logistic regression. RESULTS: Seventy traumatic popliteal artery injuries were
      identified in 68 patients with a mean age of 33 years (range: 5-88 years). The
      majority of patients were male (n = 57; 81%), and 73% sustained blunt injury.
      Associated venous injury was present in 16 (23%) cases. Associated orthopedic
      injuries included 19 (27%) dislocations and 49 (70%) fractures. The median MESS
      was 5 (range: 2-9) and the median ISS was 9 (range: 4-41). Revascularization was
      performed in 62 cases (89%). Twenty-three percent of patients had compartment
      syndrome and 56% underwent fasciotomy. Fifteen (21%) patients required
      amputation, 11% of which were primary and 10% secondary. Variables associated
      with amputation included ISS >10 compared to ISS <9 (odds ratio [OR]: 7.4; P <
      0.045), blunt injury (OR: 10.7; P = 0.009), MESS >7 (OR: 2.4; P < 0.0001), and
      fractures (OR: 0.13; P < 0.045). In a multiple exact logistic regression
      analysis, a MESS >7 (P < 0.05) was the only significant predictor of amputation.
      CONCLUSION: Patients with traumatic popliteal artery injury are at high risk for
      amputation. Blunt injury, fractures, ISS >9, and MESS >7 were associated with an
      increased odds of amputation. Although in our data, MESS was the strongest
      predictor of amputation, we recognize that MESS was previously invalidated as a
      scoring system. New methods to determine limb viability in the mangled extremity
      are needed.

PMID- 24332261
TI  - Percutaneous retrieval of an inferior vena cava filter causing right ureter
      obstruction.
AB  - Retrievable inferior vena cava filters (IVCFs) are known to provide safe and
      effective pulmonary embolism protection when used appropriately. Long-term
      complications have been reported over the past 10 years, including vena cava
      perforation, filter migration, strut fracture, and injury to adjacent structures.
      This article describes the case of a 44-year-old woman who presented with right
      ureteral obstruction from strut impingement by a Bard Recovery IVCF (Tempe, AZ,
      USA). The filter had been in place for 6 years, and the authors were successful
      in retrieving it using a percutaneous endovascular approach, despite an
      unexpected chronic right innominate vein occlusion. In addition to highlighting
      the technical feasibility of long-term retrieval, this case underscores the
      importance of an IVCF registry to improve retrieval rates. This close monitoring
      and timely retrieval of filters may help prevent serious long-term complications.

PMID- 24332262
TI  - IS30-related transposon mediated insertional inactivation of bile salt hydrolase
      (bsh1) gene of Lactobacillus plantarum strain Lp20.
AB  - Lactobacillus plantarum is a flexible and versatile microorganism that inhabits a
      variety of niches, and its genome may express up to four bsh genes to maximize
      its survival in the mammalian gut. However, the ecological significance of
      multiple bsh genes in L. plantarum is still not clearly understood. Hence, this
      study demonstrated the disruption of bile salt hydrolase (bsh1) gene due to the
      insertion of a transposable element in L. plantarum Lp20 - a wild strain of human
      fecal origin. Surprisingly, L. plantarum strain Lp20 produced a ~2.0 kb bsh1
      amplicon against the normal size (~1.0 kb) bsh1 amplicon of Bsh(+)L. plantarum
      Lp21. Strain Lp20 exhibited minimal Bsh activity in spite of having intact bsh2,
      bsh3 and bsh4 genes in its genome and hence had a Bsh(-) phenotype. Cloning and
      sequence characterization of Lp20 bsh1 gene predicted four individual open
      reading frames (ORFs) within this region. BLAST analysis of ORF1 and ORF2
      revealed significant sequence similarity to the L. plantarum bsh1 gene while ORF3
      and ORF4 showed high sequence homology to IS30-family transposases. Since, IS30
      related transposon element was inserted within Lp20 bsh1 gene in reverse
      orientation (3'-5'), it introduced several stop codons and disrupted the protein
      reading frames of both Bsh1 and transposase. Inverted terminal repeats
      (GGCAGATTG) of transposon, mediated its insertion at 255-263 nt and 1301-1309 nt
      positions of Lp20 bsh1 gene. In conclusion, insertion of IS30 related-transposon
      within the bsh1 gene sequence of L. plantarum strain Lp20 demolished the
      integrity and functionality of Bsh1 enzyme. Additionally, this transposon DNA
      sequence remains active among various Lactobacillus spp. and hence harbors the
      potential to be explored in the development of efficient insertion mutagenesis
      system.

PMID- 24332264
TI  - Combined immunodeficiency associated with homozygous MALT1 mutations.

PMID- 24332263
TI  - Randomized, double-blind, placebo-controlled trial of standardized ragweed
      sublingual-liquid immunotherapy for allergic rhinoconjunctivitis.
AB  - BACKGROUND: Sublingual immunotherapy with liquid extracts provides an appealing
      alternative to subcutaneous immunotherapy for the treatment of allergic
      rhinoconjunctivitis (ARC), but a lack of robust evidence has deterred its use in
      North America. OBJECTIVE: To determine the efficacy and tolerability of
      standardized glycerinated short ragweed sublingual allergen immunotherapy liquid
      (RW-SAIL) extract in subjects with ragweed-related ARC. METHODS: This phase 3,
      randomized, placebo-controlled trial was conducted in North America. Subjects
      (age range, 18-55 years) with or without asthma were selected based on ARC
      symptom severity and erythema skin prick reaction to short ragweed. Subjects self
      administered the maximum tolerated dose of RW-SAIL (n = 218) or placebo (n = 211)
      daily beginning approximately 8 to 16 weeks before and through the end of the
      ragweed pollen season. The primary end point was subject-assessed total combined
      daily rhinoconjunctivitis symptom and medication scores (TCS). RESULTS: During
      the entire season, there was a 43% decrease in TCS in subjects treated with RW
      SAIL compared with placebo. Similar decreases were observed in TCS between the 2
      groups during peak season (42%) and in daily symptom scores during the entire
      (42%) and peak (41%) seasons. The occurrence of adverse events was similar
      between the treatment groups; most were mild in severity. Treatment-related
      oromucosal local application site reactions occurred early and were transient and
      self-limited. No anaphylaxis occurred. CONCLUSIONS: This is the first successful
      North American confirmatory phase 3 clinical trial to demonstrate the safety and
      efficacy of a sublingual standardized ragweed allergen immunotherapy liquid
      extract for the treatment of ARC.

PMID- 24332265
TI  - Specific IgE reactivity to Tri a 36 in children with wheat food allergy.

PMID- 24332266
TI  - Clinical application of amplicon-based next-generation sequencing in cancer.
AB  - Next-generation sequencing (NGS) technology has revolutionized genomic research
      by decreasing the cost of sequencing while increasing the throughput. The focus
      now is on potential clinical applications of NGS technology for diagnostics and
      therapeutics. Clinical applications of NGS in cancer can detect clinically
      actionable genetic/genomic alterations that are critical for cancer care. These
      alterations can be of diagnostic, prognostic, or therapeutic significance. In
      certain cancers, patient risk and prognosis can be predicted based on the
      mutation profile identified by NGS. Many targeted therapies have been developed
      for cancer patients who bear specific mutations; however, choosing the right NGS
      technique for the appropriate clinical application can be challenging, especially
      in clinical oncology, where the material for NGS tests is often limited and the
      turnaround time (TAT) for cancer tests is constrained to a few days. Currently,
      amplicon-based NGS approaches have emerged as the best fit for clinical oncology.
      In this review, we focus on amplicon-based library preparation, sequencing,
      sequence data alignment and annotation, and post-analytic interpretation and
      reporting. 

PMID- 24332267
TI  - The effect of hydration on mechanical anisotropy, topography and fibril
      organization of the osteonal lamellae.
AB  - The effect of hydration on the mechanical properties of osteonal bone, in
      directions parallel and perpendicular to the bone axis, was studied on three
      length scales: (i) the mineralized fibril level (~100 nm), (ii) the lamellar
      level (~6 um); and (iii) the osteon level (up to ~30 um).We used a number of
      techniques, namely atomic force microscopy (AFM), nanoindentation and
      microindentation. The mechanical properties (stiffness, modulus and/or hardness)
      have been studied under dry and wet conditions. On all three length scales the
      mechanical properties under dry conditions were found to be higher by 30-50%
      compared to wet conditions. Also the mechanical anisotropy, represented by the
      ratio between the properties in directions parallel and perpendicular to the
      osteon axis (anisotropy ratio, designated here by AnR), surprisingly decreased
      somewhat upon hydration. AFM imaging of osteonal lamellae revealed a
      disappearance of the distinctive lamellar structure under wet conditions.
      Altogether, these results suggest that a change in mineralized fibril orientation
      takes place upon hydration.

PMID- 24332268
TI  - Clinical management and survival outcomes of gliosarcomas in the era of
      multimodality therapy.
AB  - Gliosarcoma (GSM) is a rare primary malignant brain tumour accounting for less
      than 0.5% of all intracranial tumours. It has a biphasic histological
      composition, demonstrating both gliomatous and sarcomatous elements. In clinical
      practice GSM are generally managed similarly to glioblastoma multiforme (GBM).
      However, unique features including its clinical propensity for extra-cranial
      metastasis, distinct radiological features and possible worse prognosis than GBM
      suggest that GSM may be a distinct clinico-pathological entity. Hence we reviewed
      patterns of care and outcomes for a series of Australian patients diagnosed with
      GSM in the era of combined chemo-radiotherapy. Patients were identified by
      searching the Australian Genomics and Clinical Outcomes of Glioma (AGOG) database
      and the Western Australian Interhospital Neurosurgical database. Nineteen
      patients with GSM were identified. Of these, 15 patients were diagnosed with
      primary GSM and four patients developed secondary GSM after radiation therapy for
      primary GBM. For comparative purposes, 408 primary GBM patients were identified
      from the AGOG database during the same study period. The overall median survival
      for all primary GSM patients was 9.7 months. In comparison the overall median
      survival for GBM patients recruited to the AGOG database over the same period was
      12.2 months. The median survival for secondary GSM patients from the time of
      diagnosis was 5 months. Primary and secondary GSM pose a great clinical challenge
      due to their rarity. Our study adds further evidence to support GSM as a unique
      clinical entity with a likely worse prognosis than GBM.

PMID- 24332269
TI  - Histological insights in iminodipropionitrile-induced toxicity in rats.
AB  - Iminodipropionitrile (IDPN) is a prototype nitrile compound that produces
      excitation, chorea and circling (ECC) syndrome in rodents. Previous studies have
      implicated vestibular hair cell degeneration in IDPN-induced behavioral
      abnormalities. Although the pathological changes in vestibular labyrinth of IDPN
      treated rats are well documented, the effects of IDPN on other organ systems are
      not clearly understood. We therefore examined the histopathological alterations
      in inner ear, brain, liver and kidneys of rats exposed to IDPN. Adult male Wistar
      rats were divided into two groups of six animals each. Control rats received
      normal saline whereas the IDPN group was treated with IDPN (100mg/kg, i.p.) daily
      for 7 days. All the animals were carefully observed for any behavioral
      abnormality and the dyskinetic movements including the vertical and horizontal
      head weaving, circling and backward walking were quantified. The animals were
      sacrificed on day 9 and the samples of cochlea, brain, liver and kidney were
      collected for histopathology. The results showed a direct correlation between the
      severity of behavioral deficits and the cellular damage in crista ampullaris in
      IDPN-treated rats. Histopathology of liver was severely influenced by IDPN
      treatment, leading to vacuolization of cytoplasm, distorted sinusoids,
      infiltration of mononuclear cells and necrotic zones. However, the severity of
      hepatic damage in IDPN-treated rats was independent of the magnitude of
      vestibular hair cell degeneration as well as the severity of behavioral deficits.
      Administration of IDPN in the vestibulotoxic doses did not produce any
      histological changes in the brain cortex and kidneys of rats. 

PMID- 24332271
TI  - Investigation of different bleaching conditions on the amount of elutable
      substances from nano-hybrid composites.
AB  - OBJECTIVES: To analyse the influence of irradiation time, aging before bleaching,
      and bleaching technique (home bleaching vs. in-office bleaching) on the amount of
      elutable substances from modern nano-hybrid resin-based composites (RBCs).
      METHODS: Specimens (n=5) of three nano-hybrid RBCs (Venus((r)) Diamond, Tetric
      EvoCeram((r)) and FiltekTM Supreme XTE) were irradiated for 5, 10, 20 and 40s.
      The degree of conversion (DC) was measured in real-time with Fourier transform
      infrared spectroscopy (FTIR). Specimens were bleached either directly after
      irradiation or after aging (1.5 or 6 month in distilled water at 37 degrees C)
      with Opalescence((r)) PF15% for 6h (simulation of home bleaching) or PF35% for
      0.5h (simulation of in-office bleaching) and incubated in ethanol/water (3:1) at
      37 degrees C for 7d. The eluates were analyzed by gas chromatography/mass
      spectrometry. Unbleached specimens at the above mentioned irradiation times were
      used as controls. RESULTS: Bleaching increases the amount of elutable substances.
      This amount is generally stronger influenced by aging than by polymerization time
      or concentration of the gel. 2-Hydroxyethyl methacrylate was found in amounts up
      to 334.14 (106.91) MUmol/l (Tetric EvoCeram((r)), irradiation time 5s; bleaching
      with 15% CP) as a destruction product. Diethoyxdimethylsilane was found in all
      eluates from bleached specimens, but not in the control groups. This substance
      may be formed by oxidation of 3-methacryloxy-propyltrimethoxysilane, indicating
      that the bond between inorganic filler and organic matrix might be weakened after
      bleaching. SIGNIFICANCE: Bleaching gels might alter the physical properties of
      resin-based composites, especially at low irradiation times and fresh placed
      restorations.

PMID- 24332270
TI  - Effect of salivary pellicle on antibacterial activity of novel antibacterial
      dental adhesives using a dental plaque microcosm biofilm model.
AB  - OBJECTIVES: Antibacterial primer and adhesive are promising to inhibit biofilms
      and caries. Since restorations in vivo are exposed to saliva, one concern is the
      attenuation of antibacterial activity due to salivary pellicles. The objective of
      this study was to investigate the effects of salivary pellicles on bonding agents
      containing a new monomer dimethylaminododecyl methacrylate (DMADDM) or
      nanoparticles of silver (NAg) against biofilms for the first time. METHODS:
      DMADDM and NAg were synthesized and incorporated into Scotchbond Multi-Purpose
      adhesive and primer. Specimens were either coated or not coated with salivary
      pellicles. A microcosm biofilm model was used with mixed saliva from ten donors.
      Two types of culture medium were used: an artificial saliva medium (McBain), and
      Brain Heart Infusion (BHI) medium without salivary proteins. Metabolic activity,
      colony-forming units (CFU), and lactic acid production of plaque microcosm
      biofilms were measured (n=6). RESULTS: Bonding agents containing DMADDM and NAg
      greatly inhibited biofilm activities, even with salivary pellicles. When using
      BHI, the pre-coating of salivary pellicles on resin surfaces significantly
      decreased the antibacterial effect (p<0.05). When using artificial saliva medium,
      pre-coating of salivary pellicles on resin did not decrease the antibacterial
      effect. These results suggest that artificial saliva yielded medium-derived
      pellicles on resin surfaces, which provided attenuating effects on biofilms
      similar to salivary pellicles. Compared with the commercial control, the DMADDM
      containing bonding agent reduced biofilm CFU by about two orders of magnitude.
      SIGNIFICANCE: Novel DMADDM- and NAg-containing bonding agents substantially
      reduced biofilm growth even with salivary pellicle coating on surfaces,
      indicating a promising usage in saliva-rich environment. DMADDM and NAg may be
      useful in a wide range of primers, adhesives and other restoratives to achieve
      antibacterial and anti-caries capabilities.

PMID- 24332272
TI  - Flavonoid mixture ameliorates increase in erythrocyte osmotic fragility and
      malondialdehyde concentration induced by Trypanosoma brucei brucei-infection in
      Wistar rats.
AB  - The experiment was performed with the aim of investigating the effect of a
      flavonoid mixture, Daflon(r) 500 mg (DF) on the erythrocyte fragility and
      lipoperoxidative changes, induced by Trypanosoma brucei brucei infection in
      Wistar rats. Fifty adult male rats randomly divided into five groups of 10
      animals each were used. Rats in the control group were administered (1 mL/kg)
      distilled water only, while the other groups were infected with T. brucei brucei
      and treated with Daflon(r) 500 mg and/or Diminazene aceturate. At the end of 5
      weeks, EDTA-blood samples and serum samples were collected from the rats, and
      were used to determine erythrocyte osmotic fragility (EOF) and serum
      malondialdehyde (MDA) concentration respectively. The results showed that EOF and
      MDA concentration significantly (P<0.05) increased in the infected untreated
      group when compared to the treatment groups. Treatment with Daflon(r) 500 mg and
      Diminazene aceturate significantly (P<0.05) reduced trypanosome-induced increases
      in EOF and lipoperoxidative changes, suggesting possible antioxidant properties
      of Daflon(r) 500 mg and its therapeutic value in trypanosomosis.

PMID- 24332273
TI  - Oral Recombinant Feline Interferon-Omega as an alternative immune modulation
      therapy in FIV positive cats: clinical and laboratory evaluation.
AB  - Recombinant-Feline Interferon-Omega (rFeIFN-omega) is an immune-modulator
      licensed for use subcutaneously in Feline Immunodeficiency virus (FIV) therapy.
      Despite oral protocols have been suggested, little is known about such use in FIV
      infected cats. This study aimed to evaluate the clinical improvement, laboratory
      findings, concurrent viral excretion and acute phase proteins (APPs) in naturally
      FIV-infected cats under oral rFeIFN-omega therapy (0.1 MU/cat rFeIFN-omega PO,
      SID, 90 days). 11 FIV-positive cats were treated with oral rFeIFN-omega (PO
      Group). Results were compared to previous data from 7 FIV-positive cats treated
      with the subcutaneous licensed protocol (SC Group). Initial clinical scores were
      similar in both groups. Independently of the protocol, rFeIFN-omega induced a
      significant clinical improvement of treated cats. Concurrent viral excretion and
      APP's variation were not significant in the PO Group. Oral rFeIFN-omega can be an
      effective alternative therapy for FIV-infected cats, being also an option for
      treatment follow-up in cats submitted to the licensed protocol.

PMID- 24332275
TI  - Air pollution and mortality in Europe.

PMID- 24332276
TI  - Changes in tear film, corneal topography, and refractive status in premenopausal
      women during menstrual cycle.
AB  - PURPOSE: To investigate the changes in a questionnaire based subjective
      symptomatology, tear film break-up time, tear volume, corneal topography, and
      refractive status in premenopausal women during menstrual cycle. METHODS:
      Seventeen premenopausal females and 15 healthy males were enrolled in this
      prospective study. After routine ophthalmologic examination, an ocular surface
      disease index questionnaire was administered, tear film break-up time (TBUT), and
      Schirmer I tests were performed. Keratometry readings and refractive status were
      also obtained. All examinations were repeated at day 21, day 12 and day 2.
      RESULTS: OSDI score in day 21 was significantly lower than that in day 12
      (p=0.004) and day 2 (p=0.01) in the female patients; however, no significant
      change was found in the male subjects (p>0.05). No statistically significant
      difference was found in TBUT and Schirmer I tests, keratometry, and refraction
      results in both of the female and male subjects at all of the test points
      (p>0.05). There was a significant correlation between OSDI score and TBUT
      (p=0.02, p=0.03, respectively), and Schirmer I test at day 12 (p=0.004, p=0.008,
      respectively). A significant negative correlation was found between oestrogen
      level and horizontal keratometry values at day 21 (r=-0.5, p=0.03; r=-0.4,
      p=0.04, respectively) for the right and left eyes in the female subjects.
      CONCLUSION: Our study confirms that fluctuations in the blood levels of oestrogen
      produce alterations in ocular surface equilibrium during the menstrual cycle and
      consequently affect the subjective dry eye symptoms in female patients. However,
      no ocular surface parameter changes were observed.

PMID- 24332277
TI  - Numerical simulation of patient-specific left ventricular model with both mitral
      and aortic valves by FSI approach.
AB  - Intraventricular flow is important in understanding left ventricular function;
      however, relevant numerical simulations are limited, especially when heart valve
      function is taken into account. In this study, intraventricular flow in a patient
      specific left ventricle has been modelled in two-dimension (2D) with both mitral
      and aortic valves integrated. The arbitrary Lagrangian-Eulerian (ALE) approach
      was employed to handle the large mesh deformation induced by the beating
      ventricular wall and moving leaflets. Ventricular wall deformation was predefined
      based on MRI data, while leaflet dynamics were predicted numerically by fluid
      structure interaction (FSI). Comparisons of simulation results with in vitro and
      in vivo measurements reported in the literature demonstrated that numerical
      method in combination with MRI was able to predict qualitatively the patient
      specific intraventricular flow. To the best of our knowledge, we are the first to
      simulate patient-specific ventricular flow taking into account both mitral and
      aortic valves. 

PMID- 24332274
TI  - Effects of long-term exposure to air pollution on natural-cause mortality: an
      analysis of 22 European cohorts within the multicentre ESCAPE project.
AB  - BACKGROUND: Few studies on long-term exposure to air pollution and mortality have
      been reported from Europe. Within the multicentre European Study of Cohorts for
      Air Pollution Effects (ESCAPE), we aimed to investigate the association between
      natural-cause mortality and long-term exposure to several air pollutants.
      METHODS: We used data from 22 European cohort studies, which created a total
      study population of 367,251 participants. All cohorts were general population
      samples, although some were restricted to one sex only. With a strictly
      standardised protocol, we assessed residential exposure to air pollutants as
      annual average concentrations of particulate matter (PM) with diameters of less
      than 2.5 MUm (PM2.5), less than 10 MUm (PM10), and between 10 MUm and 2.5 MUm
      (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen
      oxides (NO2 and NOx), with land use regression models. We also investigated two
      traffic intensity variables-traffic intensity on the nearest road (vehicles per
      day) and total traffic load on all major roads within a 100 m buffer. We did
      cohort-specific statistical analyses using confounder models with increasing
      adjustment for confounder variables, and Cox proportional hazards models with a
      common protocol. We obtained pooled effect estimates through a random-effects
      meta-analysis. FINDINGS: The total study population consisted of 367,251
      participants who contributed 5,118,039 person-years at risk (average follow-up
      13.9 years), of whom 29,076 died from a natural cause during follow-up. A
      significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13)
      per 5 MUg/m(3) was recorded. No heterogeneity was noted between individual cohort
      effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised
      even when we included only participants exposed to pollutant concentrations lower
      than the European annual mean limit value of 25 MUg/m(3) (HR 1.06, 95% CI 1.00
      1.12) or below 20 MUg/m(3) (1.07, 1.01-1.13). INTERPRETATION: Long-term exposure
      to fine particulate air pollution was associated with natural-cause mortality,
      even within concentration ranges well below the present European annual mean
      limit value. FUNDING: European Community's Seventh Framework Program (FP7/2007
      2011).

PMID- 24332278
TI  - Incidence of elevation of serum thyroid-stimulating hormone during controlled
      ovarian hyperstimulation for in vitro fertilization.
AB  - OBJECTIVE: To evaluate the rate of euthyroid women encountering an elevation of
      serum TSH above the threshold of 2.5 mIU/L during controlled ovarian
      hyperstimulation (COH) for IVF. STUDY DESIGN: Six-month prospective cohort study
      on 175 consecutive euthyroid women undergoing their first IVF cycle. Serum TSH
      assessments were performed before COH, at the time of hCG administration and at
      +16 days after hCG administration. Women were eligible if serum TSH tested the
      month preceding the IVF cycle was 0.4-2.5 mIU/L. A history of thyroid disorders
      was an exclusion criterion. RESULTS: Serum concentrations of TSH at the three
      scheduled assessments were 1.5+/-0.5, 2.2+/-1.0 and 2.1+/-1.1 mIU/L,
      respectively. A statistically significant increase occurred between basal levels
      and levels at the time of hCG administration (p<0.001). Afterwards, levels
      remained stable (p=0.49). Serum TSH at the time of hCG administration exceeded
      the threshold of 2.5 mIU/L in 61 subjects, corresponding to 35% (95% CI: 28-42%).
      At +16 days after hCG administration, this event was observed in 47 subjects
      (27%, 95% CI: 21-34%). Baseline characteristics of women who did and did not
      exceed the threshold were similar apart from basal serum TSH, which was higher in
      the former group. The OR was 7.6 (95%CI: 2.9-20.2) per mIU/L (p<0.001). Cycle
      outcome and pregnancy rate were also similar. CONCLUSION: Serum TSH exceeds the
      threshold of 2.5 mIU/L during COH in one out of three women who are euthyroid
      prior to enter an IVF cycle. Further evidence is warranted to elucidate the
      clinical relevance of our findings.

PMID- 24332279
TI  - Imaging of arterial inflammation: keeping our cool on a hot topic.

PMID- 24332280
TI  - Prediction of MACE after ACS: demographics and angiography versus imaging.

PMID- 24332281
TI  - MR spectroscopy of cholesteryl ester in human atherosclerosis.

PMID- 24332282
TI  - RV is doing well at high altitudes!--Always?

PMID- 24332283
TI  - Surgical thresholds for bicuspid aortic valve associated aortopathy.
AB  - OBJECTIVES: This systematic review seeks to present the outcomes of the natural
      history of aortopathy associated with bicuspid aortic valve (ABAV) and after
      interventions. BACKGROUND: Aortopathy is common in patients with ABAV, and early
      intervention has been proposed to reduce the risk of dissection. In asymptomatic
      patients, the timing of surgical management is based upon imaging of aortic size,
      but the actual threshold is based upon observational data and expert opinion. As
      evidence of high risk would justify early intervention, we sought to define the
      natural history of this condition and after interventions. METHODS: We undertook
      a systemic review of the evidence from observational studies of ABAV published up
      to June 2013. The primary outcome was annualized all-cause mortality. Secondary
      outcomes included acute aortic events, rates of aneurysm enlargement, and peri
      operative complications. A random-effects model was used to combine outcomes. A
      meta-regression was undertaken to assess the impact of potential covariates.
      RESULTS: The 32 eligible papers involved 11,045 patients (9,441 BAV and 1,604
      control subjects, age 46 +/- 14 years). There were 3 major groups, nonoperated
      bicuspid aortic valve (BAV) patients (ages from 30 to 40 years), patients after
      aortic surgery (generally 40 to 60 years of age) and after isolated valve
      replacement (>60 years of age). The respective annualized mortality of
      nonoperated BAV patients was 0.56% (95% confidence interval [CI]: 0.13 to 0.99),
      compared with 0.78% (95% CI: 0.20 to 1.36) in patients after aortic surgery and
      2.39% (95% CI: 1.61 to 3.16) after isolated valve replacement. The annualized
      acute event rate in nonoperated BAV patients was 0.29% (95% CI: 0.23 to 0.35),
      this risk being no different from that of a tricuspid aortic valve (risk ratio:
      0.68, 95% CI: 0.34 to 1.36). In the post-surgical series, 30-day mortality varied
      from 0% to 2.5%, and the risk of acute events was 0.16% (95% CI: 0.0 to 0.32) in
      patients after aortic surgery and 0.68% (95% CI: 0.42 to 0.94) after isolated
      valve replacement. Aortic dilation was at a rate of 0.16 mm/year over 6 decades
      in healthy BAV subjects and 1.1 +/- 0.15 mm/year in older aortic valve
      replacement patients. CONCLUSIONS: The risk associated with ABAV varies according
      to age and clinical setting. Nonetheless, despite aortic dilatation, the acute
      aortic event risk of ABAV appears low in current practice. Decision-making
      regarding the timing of intervention needs to be made on the basis of the balance
      between this low risk and both the morbidity and mortality of surgery.

PMID- 24332284
TI  - Aortic surgery for ascending aortic aneurysms under 5.0 cm in diameter in the
      presence of bicuspid aortic valve.
AB  - Aneurysm of the ascending aorta may cause acute type A aortic dissection, and the
      primary aim of a prophylactic operation is avoidance of this life-threatening
      complication. Current guidelines recommend prophylactic replacement of the
      aneurysmal ascending aorta at a diameter of >=5.5 cm. However, several reports
      have shown that nearly 50% of patients with an acute type A aortic dissection
      present with an aortic diameter <5.5 cm. It is controversial how to best respond
      to these observations. Because surgical advances have led to a reduction of early
      surgical mortality between 1% and 3%, many clinicians believe that surgery is
      warranted in smaller aortas. Given the frequency of a bicuspid aortic valve
      (BAV), such a strategy has health implications for this population.

PMID- 24332286
TI  - Imaging of adult atrial septal defects with CT angiography.

PMID- 24332287
TI  - Noninvasive voltage and activation mapping of ARVD/C using ECG imaging.

PMID- 24332285
TI  - The advancing clinical impact of molecular imaging in CVD.
AB  - Molecular imaging seeks to unravel critical molecular and cellular events in
      living subjects by providing complementary biological information to current
      structural clinical imaging modalities. In recent years, molecular imaging
      efforts have marched forward into the clinical cardiovascular arena, and are now
      actively illuminating new biology in a broad range of conditions, including
      atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm,
      cardiomyopathy, and valvular disease. Development of novel molecular imaging
      reporters is occurring for many clinical cardiovascular imaging modalities
      (positron emission tomography, single-photon emission computed tomography,
      magnetic resonance imaging), as well as in translational platforms such as
      intravascular fluorescence imaging. The ability to image, track, and quantify
      molecular biomarkers in organs not routinely amenable to biopsy (e.g., the heart
      and vasculature) open new clinical opportunities to tailor therapeutics based on
      a cardiovascular disease molecular profile. In addition, molecular imaging is
      playing an increasing role in atherosclerosis drug development in phase II
      clinical trials. Here, we present state-of-the-art clinical cardiovascular
      molecular imaging strategies, and explore promising translational approaches
      positioned for clinical testing in the near term. 

PMID- 24332288
TI  - Impact of regurgitant orifice height for mechanism of aortic regurgitation.

PMID- 24332289
TI  - Coronary plaque composition and post-PCI complications in NSTEMI.

PMID- 24332290
TI  - The ethics of publishing medical imaging research.

PMID- 24332292
TI  - Papillary thyroid carcinoma associated to squamous cell carcinoma.

PMID- 24332293
TI  - Tool use and manual actions: the human body as a means versus an end.

PMID- 24332294
TI  - Data modelling in corpus linguistics: how low may we go?
AB  - Corpus linguistics allows researchers to process millions of words. However, the
      more words we analyse, i.e., the more data we acquire, the more urgent the call
      for correct data interpretation becomes. In recent years, a number of studies saw
      the light attempting to profile some prolific authors' linguistic decline,
      linking this decline to pathological conditions such as Alzheimer's Disease (AD).
      However, in line with the nature of the (literary) work that was analysed,
      numbers alone do not suffice to 'tell the story'. The one and only objective of
      using statistical methods for the analysis of research data is to tell a story-
      what happened, when, and how. In the present study we describe a computerised but
      individualised approach to linguistic analysis--we propose a unifying approach,
      with firm grounds in Information Theory, that, independently from the specific
      parameter being investigated, guarantees to produce a robust model of the
      temporal dynamics of an author's linguistic richness over his or her lifetime. We
      applied this methodology to six renowned authors with an active writing life of
      four decades or more: Iris Murdoch, Gerard Reve, Hugo Claus, Agatha Christie,
      P.D. James, and Harry Mulisch. The first three were diagnosed with probable
      Alzheimer Disease, confirmed post-mortem for Iris Murdoch; this same condition
      was hypothesized for Agatha Christie. Our analysis reveals different evolutive
      patterns of lexical richness, in turn plausibly correlated with the authors'
      different conditions.

PMID- 24332296
TI  - Patterns and trends in human papillomavirus-related diseases in Central and
      Eastern Europe and Central Asia.
AB  - This article provides an overview of cervical cancer and other human
      papillomavirus (HPV)-related diseases in Central and Eastern Europe (Albania,
      Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary,
      Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, and
      the Former Yugoslav Republic [FYR] of Macedonia) and Central Asia (Armenia,
      Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Republic of Moldova, the
      Russian Federation, Tajikistan, Turkmenistan, Ukraine and Uzbekistan). Despite
      two- to three-fold variations, cervical cancer incidence rates are high in many
      countries in these two regions relative to other populations on the European and
      Asian continents. In Central and Eastern Europe, Romania and the FYR of Macedonia
      had the highest rates in 2008 alongside Bulgaria, Lithuania and Serbia, while in
      Central Asia, rates are elevated in Kyrgyzstan (the highest rates across the
      regions), Kazakhstan and Armenia. In each of these countries, at least one woman
      in 50 develops cervical cancer before the age of 75. The high cervical cancer
      burden is exacerbated by a lack of effective screening and an increasing risk of
      death from the disease among young women, as observed in Belarus, Tajikistan,
      Kyrgyzstan, Armenia, Azerbaijan, Ukraine, the Russian Federation and Kazakhstan.
      In several countries with longstanding cancer registries of reasonable quality
      (Belarus, Estonia and the Russian Federation), there are clear birth cohort
      effects; the risk of onset of cervical cancer is increasing in successive
      generations of women born from around 1940-50, a general phenomenon indicative of
      changing sexual behaviour and increasing risk of persistent HPV infection. There
      are limited data for other HPV-related cancers and other diseases at present in
      these countries. While options for reducing the HPV-related disease burden are
      resource-dependent, universal HPV vaccination with enhanced screening would
      maximally reduce the burden of cervical cancer in the countries within the two
      regions. It is hoped that the expanded second edition of the European Guidelines
      will finally kick-start effective interventions in many of these countries that
      still lack organised programmes. This article forms part of a regional report
      entitled "Comprehensive Control of HPV Infections and Related Diseases in the
      Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement
      7, 2013. Updates of the progress in the field are presented in a separate
      monograph entitled "Comprehensive Control of HPV Infections and Related Diseases"
      Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24332297
TI  - Human papillomavirus prevalence and type-distribution, cervical cancer screening
      practices and current status of vaccination implementation in Russian Federation,
      the Western countries of the former Soviet Union, Caucasus region and Central
      Asia.
AB  - Limited data are available on the burden of human papillomavirus (HPV) and its
      associated diseases in the Russian Federation, the Western Countries of the
      former Soviet Union (Belarus, Republic of Moldova, Ukraine), the Caucasus region
      and Central Asia (Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan,
      Tajikistan, Turkmenistan, Uzbekistan). Both the incidence and mortality rate of
      cervical cancer are higher in these countries than in most Western European
      countries. In this article, we review available data on HPV prevalence and type
      distribution in women with normal cytology, women from the general population,
      cervical precancerous lesions and cervical cancer, as well as data on national
      policies of cervical cancer screening and HPV vaccination initiatives in these
      countries. Based on scarce data from the 12 countries, the high-risk HPV (hrHPV)
      prevalence among 5226 women with normal cytology ranged from 0.0% to 48.4%. In
      women with low-grade cervical lesions, the hrHPV prevalence among 1062 women
      varied from 29.2% to 100%. HrHPV infection in 565 women with high-grade cervical
      lesions ranged from 77.2% to 100% and in 464 invasive cervical cancer samples
      from 89.8% to 100%. HPV16 was the most commonly detected hrHPV genotype in all
      categories. As the HPV genotype distribution in cervical diseases seems to be
      similar to that found in Western Europe the implementation of HPV testing in
      screening programs might be beneficial. Opportunistic screening programs, the
      lack of efficient call-recall systems, low coverage, and the absence of quality
      assured cytology with centralized screening registry are major reasons for low
      success rates of cervical cancer programs in many of the countries. Finally, HPV
      vaccination is currently not widely implemented in most of the twelve countries
      mainly due to pricing, availability, and limited awareness among public and
      health care providers. Country-specific research, organized nationwide screening
      programs, registries and well defined vaccination policies are needed. This
      article forms part of a Regional Report entitled "Comprehensive Control of HPV
      Infections and Related Diseases in the Central and Eastern Europe and Central
      Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in
      the field are presented in a separate monograph entitled "Comprehensive Control
      of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24332295
TI  - Comprehensive control of human papillomavirus infections and related diseases.
AB  - Infection with human papillomavirus (HPV) is recognized as one of the major
      causes of infection-related cancer worldwide, as well as the causal factor in
      other diseases. Strong evidence for a causal etiology with HPV has been stated by
      the International Agency for Research on Cancer for cancers of the cervix uteri,
      penis, vulva, vagina, anus and oropharynx (including base of the tongue and
      tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide,
      4.8% were attributable to HPV infection, with substantially higher incidence and
      mortality rates seen in developing versus developed countries. In recent years,
      we have gained tremendous knowledge about HPVs and their interactions with host
      cells, tissues and the immune system; have validated and implemented strategies
      for safe and efficacious prophylactic vaccination against HPV infections; have
      developed increasingly sensitive and specific molecular diagnostic tools for HPV
      detection for use in cervical cancer screening; and have substantially increased
      global awareness of HPV and its many associated diseases in women, men, and
      children. While these achievements exemplify the success of biomedical research
      in generating important public health interventions, they also generate new and
      daunting challenges: costs of HPV prevention and medical care, the implementation
      of what is technically possible, socio-political resistance to prevention
      opportunities, and the very wide ranges of national economic capabilities and
      health care systems. Gains and challenges faced in the quest for comprehensive
      control of HPV infection and HPV-related cancers and other disease are summarized
      in this review. The information presented may be viewed in terms of a reframed
      paradigm of prevention of cervical cancer and other HPV-related diseases that
      will include strategic combinations of at least four major components: 1) routine
      introduction of HPV vaccines to women in all countries, 2) extension and
      simplification of existing screening programs using HPV-based technology, 3)
      extension of adapted screening programs to developing populations, and 4)
      consideration of the broader spectrum of cancers and other diseases preventable
      by HPV vaccination in women, as well as in men. Despite the huge advances already
      achieved, there must be ongoing efforts including international advocacy to
      achieve widespread-optimally universal-implementation of HPV prevention
      strategies in both developed and developing countries. This article summarizes
      information from the chapters presented in a special ICO Monograph 'Comprehensive
      Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5,
      2012. Additional details on each subtopic and full information regarding the
      supporting literature references may be found in the original chapters. 

PMID- 24332298
TI  - Human papillomavirus prevalence and type-distribution, cervical cancer screening
      practices and current status of vaccination implementation in Central and Eastern
      Europe.
AB  - We present a review of current cervical cancer screening practices, the
      implementation status of vaccination against human papillomaviruses (HPV) and
      available data concerning the burden of HPV infection and HPV type-specific
      distribution in 16 Central and Eastern European countries: Albania, Bosnia and
      Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia,
      Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and the Former
      Yugoslav Republic (FYR) of Macedonia. Since published data were relatively
      scarce, two detailed surveys were conducted during August-October 2011 and in
      January 2013 to obtain relevant and updated information. The mean prevalence of
      HPV infection in 8610 women with normal cervical cytology from the region was
      12.6%, with HPV16 being the most frequent HPV type. The overall HPV DNA
      prevalence in women with high-grade cervical lesions was 78.1%. HPV DNA was found
      in 86.6% of cervical cancers; the combined prevalence of HPV16/18 among HPV
      positive cases was 87.5%. The overall HPV DNA prevalence in genital warts and
      laryngeal papillomas was 94.8% and 95.2%, respectively, with HPV6 and HPV11 being
      the most frequent types. Opportunistic and organized cervical screening, mainly
      based on conventional cytology, is performed in nine and seven countries in the
      region, respectively, with the proposed age of the start of screening ranging
      from 20 to 30 years and the estimated coverage ranging from a few percent to over
      70%. At least one of the current HPV prophylactic vaccines is registered in all
      Central and Eastern European countries except Montenegro. Only Bulgaria, Czech
      Republic, FYR Macedonia, Latvia, Romania and Slovenia have actually integrated
      HPV vaccination into their national immunization programme and currently provide
      routine vaccination free of charge to the primary target population. The key
      reasons for lack of implementation of HPV vaccination into the national
      immunization programme are high vaccine cost and negative public perception. This
      article forms part of a regional report entitled "Comprehensive Control of HPV
      Infections and Related Diseases in the Central and Eastern Europe and Central
      Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in
      the field are presented in a separate monograph entitled "Comprehensive Control
      of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24332299
TI  - Cost-effectiveness of cervical cancer prevention in Central and Eastern Europe
      and Central Asia.
AB  - We studied the cost-effectiveness of cervical cancer prevention strategies in the
      Central and Eastern Europe and Central Asia (CEECA) region. The cost
      effectiveness of human papillomavirus (HPV)16/18 vaccination of 12 year-old girls
      was calculated for 28 countries, under the assumption that vaccination prevents
      70% of all cervical cancer cases and that cervical cancer and all-cause mortality
      rates are stable without vaccination. At three-dose vaccination costs of I$ 100
      per vaccinated girl (currency 2005 international dollars), HPV16/18 vaccination
      was very cost-effective in 25 out of 28 countries using the country's gross
      domestic product (GDP) per capita as cost-effectiveness threshold (criterion by
      World Health Organization). A three-dose vaccination cost of I$ 100 is within the
      current range of vaccine costs in European immunization programs, and therefore
      our results indicate that HPV vaccination may be good value for money. To
      evaluate the cost-effectiveness of cervical cancer screening combined with
      vaccination, we calibrated a published simulation model to HPV genotype data
      collected in Slovenia, Poland, and Georgia. The screening interval was varied at
      3, 6, and 10 years starting at age 25 or 30 and ending at age 60. In Slovenia and
      Poland, combined vaccination and 10-yearly HPV (DNA) screening (vaccination
      coverage 70%, screening coverage per round 70%) was very cost-effective when the
      cost of three-dose vaccination was I$ 100 per vaccinated girl. More intensive
      screening was very cost-effective when the screening coverage per round was 30%
      or 50%. In Georgia, 10-yearly Pap screening was very cost-effective in
      unvaccinated women. Vaccination combined with 10-yearly HPV screening was likely
      to be cost-effective if the three-dose vaccination cost was I$ 50 per vaccinated
      girl. To conclude, cervical cancer prevention strategies utilizing both HPV16/18
      vaccination and HPV screening are very cost-effective in countries with
      sufficient resources. In low-resource settings, low vaccine pricing is essential
      for strategies of combined vaccination and screening to be cost-effective. This
      article forms part of a regional report entitled "Comprehensive Control of HPV
      Infections and Related Diseases in the Central and Eastern Europe and Central
      Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in
      the field are presented in a separate monograph entitled "Comprehensive Control
      of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. 

PMID- 24332300
TI  - Recommendations for cervical cancer prevention in Central and Eastern Europe and
      Central Asia.

PMID- 24332301
TI  - Prevention of cervical cancer in Central and Eastern Europe and Central Asia: a
      challenge for the future.

PMID- 24332302
TI  - The path to eliminate cervical cancer in the world and the challenges of
      professional education.

PMID- 24332303
TI  - [Ankle brachial index: motivations, training, and practices among 165 general
      practitioners in Ile-de-France].
AB  - Peripheral arterial disease (PAD) is under-diagnosed despite its predictive value
      for cardiovascular mortality. The ankle brachial index (ABI), a simple reliable
      measure recommended by the French health authorities to detect and evaluate the
      severity of PAD, is used by too few general practitioners (GPs). OBJECTIVE: This
      study aimed at identifying motivations and barriers for using ABI in general
      practice. METHOD: A representative, descriptive, cross-sectional survey was
      conducted amongst 165 GPs practicing in Ile-de-France who were interviewed using
      stratified quotas. RESULTS: Although 1 out of 5 GPs considered ABI to be an
      irrelevant indicator, most had a favorable opinion about its use (OR: 4.9 [CI 95
      %: 4.2-5.7]). Only 42 % (CI 95 %: 34 %-49 %) of GPs knew ABI was recommended by
      the health authorities. This information had a critical impact on the acceptance
      of ABI relevancy (OR: 3.7 [CI 95 %: 3.2-4.2]). Training reinforced acceptance
      (OR: 5.0 [CI 95 %: 4.4-5.6]) and pre-residency education provided a better
      understanding of ABI (OR: 2.8 [CI 95 %: 2.3-3.4]). Time needed to measure ABI was
      the main barrier (OR: 0.6 [CI 95 %: 0.6-0.7]). A Doppler-calculation kit (OR:
      11.8 [CI 95 %: 8.9-15.6]), equipment cost<=300Euros (OR: 3.4 [CI 99 %: 3.0-3.9]),
      a specific fee in addition to the regular consultation fee (OR: 2.6 [CI 95 %: 2.3
      3.0]) and inclusion of ABI in the GP's evaluation scheme (OR: 2.6 [CI 95 %: 2.3
      2.9]) would motivate more GPs. Seven out of 10 GPs agreed that ABI has a positive
      impact on patient adherence to treatment and follow-up, but ABI remained
      underexploited for symptomatic patients (OR: 0.4 [CI 95 %: 0.3-0.4]). CONCLUSION:
      Better communication and training together with an upgraded status for ABI would
      provide motivation for GPs to measure ABI.

PMID- 24332304
TI  - CO2 laser for the treatment of rhinophyma.

PMID- 24332305
TI  - The BCG Moreau RD16 deletion inactivates a repressor reshaping transcription of
      an adjacent gene.
AB  - The Brazilian anti-tuberculosis vaccine strain Mycobacterium bovis bacillus
      Calmette-Guerin (BCG) BCG Moreau is unique in having a deletion of 7608 bp (RD16)
      that results in the truncation of a putative TetR transcriptional regulator, the
      ortholog of Mycobacterium tuberculosis rv3405c, BCG_M3439c. We investigated the
      effect of this truncation on the expression of the rv3406 ortholog (BCG_M3440),
      lying 81 bp downstream in the opposite orientation. RT-PCR and western blot
      experiments show that rv3406 mRNA and Rv3406 accumulate in BCG Moreau but not in
      BCG Pasteur (strain that bears an intact rv3405c), suggesting this to be a result
      of rv3405c truncation. Recombinant Rv3405c forms a complex with the rv3405c
      rv3406 intergenic region, which contains a characteristic transcription factor
      binding site, showing it to have DNA binding activity. Complementation of M.
      bovis BCG Moreau with an intact copy of rv3405c abolishes Rv3406 accumulation.
      These results show that Rv3405c is a DNA binding protein that acts as a
      transcriptional repressor of rv3406. 

PMID- 24332306
TI  - The G8 Dementia Research Summit--a starter for eight?

PMID- 24332307
TI  - The Confidential Inquiry into premature deaths of people with intellectual
      disabilities in the UK: a population-based study.
AB  - BACKGROUND: The Confidential Inquiry into premature deaths of people with
      intellectual disabilities in England was commissioned to provide evidence about
      contributory factors to avoidable and premature deaths in this population.
      METHODS: The population-based Confidential Inquiry reviewed the deaths of people
      with intellectual disabilities aged 4 years and older who had been registered
      with a general practitioner in one of five Primary Care Trust areas of southwest
      England, who died between June 1, 2010, and May 31, 2012. A network of health,
      social-care, and voluntary-sector services; community contacts; and statutory
      agencies notified the Confidential Inquiry of all deaths of people with
      intellectual disabilities and provided core data. The Office for National
      Statistics provided data about the coding of individual cause of death
      certificates. Deaths were described as avoidable (preventable or amenable),
      according to Office for National Statistics definitions. Contributory factors to
      deaths were identified and quantified by the case investigator, verified by a
      local review panel meeting, and agreed by the Confidential Inquiry overview
      panel. Contributory factors were grouped into four domains: intrinsic to the
      individual, within the family and environment, care provision, and service
      provision. The deaths of a comparator group of people without intellectual
      disabilities but much the same in age, sex, and cause of death and registered at
      the same general practices as those with intellectual disabilities were also
      investigated. FINDINGS: The Confidential Inquiry reviewed the deaths of 247
      people with intellectual disabilities. Nearly a quarter (22%, 54) of people with
      intellectual disabilities were younger than 50 years when they died, and the
      median age at death was 64 years (IQR 52-75). The median age at death of male
      individuals with intellectual disabilities was 65 years (IQR 54-76), 13 years
      younger than the median age at death of male individuals in the general
      population of England and Wales (78 years). The median age at death of female
      individuals with intellectual disabilities was 63 years (IQR 54-75), 20 years
      younger than the median age at death for female individuals in the general
      population (83 years). Avoidable deaths from causes amenable to change by good
      quality health care were more common in people with intellectual disabilities
      (37%, 90 of 244) than in the general population of England and Wales (13%).
      Contributory factors to premature deaths in a subset of people with intellectual
      disabilities compared with a comparator group of people without intellectual
      disabilities included problems in advanced care planning (p=0.0003), adherence to
      the Mental Capacity Act (p=0.0008), living in inappropriate accommodation
      (p<0.0001), adjusting care as needs changed (p=0.009), and carers not feeling
      listened to (p=0.006). INTERPRETATION: The Confidential Inquiry provides evidence
      of the substantial contribution of factors relating to the provision of care and
      health services to the health disparities between people with and without
      intellectual disabilities. It is imperative to examine care and service provision
      for this population as potentially contributory factors to their deaths--factors
      that can largely be ameliorated. FUNDING: Department of Health for England.

PMID- 24332308
TI  - Deaths of people with intellectual disabilities in the UK.

PMID- 24332309
TI  - Surgery and global health: a Lancet Commission.

PMID- 24332310
TI  - Arsenolipids show different profiles in muscle tissues of four commercial fish
      species.
AB  - Identification of arsenolipids in biological samples is today a challenge and in
      particular the need for speciation data for toxicological assessment. Fish is one
      of the major contributors of arsenic in diet. However, the majority of work in
      this area has only focused on the water soluble compounds. The aim of this study
      is to provide some data on total arsenic and in particular to gain insights into
      the types of arsenolipids in the muscle tissues of four commercial and commonly
      consumed fish species. Determination of total arsenic was carried out by ICP-MS
      following microwave-assisted acid digestion of the samples and the concentrations
      found for total arsenic in the muscles ranged from 4.8 to 6.0MUg/gd.w. Sequential
      extraction was carried out using hexane and MeOH/DCM followed by reversed phase
      HPLC-ICP-MS/ESI-MS analysis of the MeOH/DCM fraction. Eight arsenolipids
      including three arsenic fatty acids (AsFAs) and five arsenic hydrocarbons (AsHCs)
      were identified. The result showed that fish with higher arsenolipid (AsLp)
      content (brill and sardine) are dominated by AsHC, while those with the smaller
      proportion of AsLp (mackerel and red mullet) have predominately arsenic in the
      form of AsFA. 

PMID- 24332311
TI  - Tissue hemoglobin monitoring is unable to follow variations of arterial
      hemoglobin during transitions from pulsatile to constant flow in cardiac surgery.
AB  - OBJECTIVE: To test whether the variations of tissue hemoglobin concentration
      (?THb) measured by the FORE-SIGHT(TM) cerebral oximeter can accurately detect
      changes in arterial hemoglobin concentration (?AHb) before, during, and after
      cardiopulmonary bypass. DESIGN: A prospective clinical study. SETTING: Cardiac
      surgery operating room. PARTICIPANTS: Thirty patients scheduled for cardiac
      surgery. INTERVENTIONS: Tissue hemoglobin concentration (THb) was recorded
      continuously via 2 sensors applied on the forehead and connected to the cerebral
      oximeter. Arterial hemoglobin concentration (AHb) was measured in a hematology
      analyzer laboratory. Hemodynamic and respiratory parameters as well as
      epidemiologic data also were noted. Data were collected at 3 perioperative times:
      After induction of anesthesia, 10 minutes after cardioplegia, and at the end of
      the surgery. MEASUREMENTS AND MAIN RESULTS: Ninety pairs of data were collected.
      The coefficient of linear regression between ?THb and ?AHb was 0.4 (p<0.001).
      After exclusion of Hb variations<5%, the trending ability of THb to predict ?AHb
      was 87%. However, the Bland and Altman plot graph for THb and AHb showed major
      limits of agreement (2.4 times the standard deviation). Central venous pressure
      and carbon dioxide tension were linked independently and positively with THb (p =
      0.03). CONCLUSIONS: Continuous monitoring of THb cannot accurately track
      variations of AHb during the transition from pulsatile to continuous flow and
      vice versa in cardiac surgery. Local hemodynamic factors such as PaCO2 and
      vasodilation significantly impact THb. In this setting, THb monitoring should not
      be used to guide eventual blood transfusion management.

PMID- 24332312
TI  - Racial differences in skin cancer awareness and surveillance practices at a
      public hospital dermatology clinic.
AB  - BACKGROUND: Patients from ethnoracial minority groups have lower incidence rates
      of melanoma compared with whites, but are more likely to have advanced melanomas
      at diagnosis and lower survival. Infrequent skin cancer screening and poor
      melanoma awareness may contribute to these disparities. OBJECTIVE: The purpose of
      this survey study was to evaluate skin cancer surveillance behaviors and
      awareness among patients attending a dermatology clinic at a public hospital in
      New York City. METHODS: Surveys were administered to 152 patients from April to
      June 2012. RESULTS: In all, 16% of patients previously had a total body skin
      examination for cancer, 11% were taught by a health care practitioner how to
      perform skin self-examinations, and 15% perform skin self-examinations. More
      whites had a total body skin examination compared with minorities (49% vs 5%).
      Only 33% of patients previously given a diagnosis of skin cancer performed skin
      self-examinations. Patients possessed a poor ability to recognize features
      suspicious for melanoma, with minorities (especially Hispanics) performing worse
      than whites. LIMITATIONS: Small sample size is a limitation. CONCLUSIONS: Few
      patients engage in skin cancer screening behaviors and their knowledge about
      melanoma is poor, with minorities demonstrating lower understanding than whites.
      Our findings emphasize the need for improved patient education about
      characteristics of melanoma, regardless of race.

PMID- 24332313
TI  - Elevated formaldehyde concentration in "Brazilian keratin type" hair
      straightening products: a cross-sectional study.
AB  - BACKGROUND: Brazilian keratin treatment (BKT) and similar straightening products
      fix and retain a straight shape even when the hair is wet. Unacceptably high
      concentrations of formaldehyde have been reported in such products. OBJECTIVE: We
      sought to measure the formaldehyde concentration in all BKT brands marketed in
      South Africa in 2012. METHODS: We quantified formaldehyde by high-performance
      liquid chromatography with ultraviolet light detection after derivatization with
      dinitrophenylhydrazine. All components of 7 identified commercial brands were
      each tested 3 times. RESULTS: The maximum safe concentration of formaldehyde set
      by the US Cosmetic Ingredient Review Expert Panel is less than 0.2%. Of the 7
      commercial BKT brands, 6 had formaldehyde levels that ranged from 0.96% to 1.4%,
      ie, 5 times higher than the recommended level; these included 5 brands labeled
      formaldehyde-free. LIMITATIONS: The study is limited by not including all
      internationally available BKT products. CONCLUSIONS: Formaldehyde concentrations
      in BKT products may exceed recommended levels and serve as a health hazard.
      Industry monitoring is needed to improve compliance and protection of
      hairdressers and consumers.

PMID- 24332314
TI  - The methotrexate polyglutamate assay supports the efficacy of methotrexate for
      severe inflammatory skin disease in children.
AB  - BACKGROUND: The methotrexate (MTX) polyglutamate assay has been validated in
      adults with arthritis. OBJECTIVE: We sought to assess clinical response rates and
      the value of the methotrexate polyglutamate assay in MTX-treated children with
      inflammatory skin diseases. METHODS: In this retrospective review, 46 MTX-treated
      children with a diagnosis of atopic dermatitis, psoriasis, or psoriasis-eczema
      overlap were serially assessed with the methotrexate polyglutamate assay.
      RESULTS: In all, 38 children (83%) achieved good to excellent response: 27 (59%)
      within 12 weeks and 11 (24%) after dose-adjustment. Good to excellent responses
      were highest for psoriasis/overlap: 15 of 16 (94%), compared with 23 of 30 (77%)
      with atopic dermatitis. Mean maximum polyglutamate levels were 31.5 nmol/L for
      responders versus 18.1 nmol/L for nonresponders (P = .035). This difference was
      also significant for the subset with atopic dermatitis, but not for those with
      psoriasis/overlap. After dose modification, late responders ultimately achieved a
      significantly higher mean maximum methotrexate polyglutamate assay (41.9 nmol/L)
      compared with nonresponders (P = .002). LIMITATIONS: Retrospective design and
      small sample size were limitations. CONCLUSIONS: MTX is an effective treatment
      for the majority of children with inflammatory skin diseases, but a subset
      requires dose modification to achieve good to excellent response. Methotrexate
      polyglutamate assay levels reflect response to treatment, but are most useful to
      support dose modification among children who fail to respond within 12 weeks.

PMID- 24332315
TI  - Differential effects of eicosapentaenoic acid and docosahexaenoic acid in
      promoting the differentiation of 3T3-L1 preadipocytes.
AB  - The objective of this study was to determine the effects of enrichment with n-3
      fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the
      differentiation of 3T3-L1 preadipocytes. Enrichment with DHA but not EPA
      significantly increased the differentiation markers compared to control
      differentiated cells. DHA compared to EPA treatment led to a greater increase in
      adiponectin secretion and, conditioned media collected from DHA treated cells
      inhibited monocyte migration. Moreover, DHA treatment resulted in inhibition of
      pro-inflammatory signaling pathways. DHA treated cells predominantly accumulated
      DHA in phospholipids whereas EPA treatment led to accumulation of both EPA and
      its elongation product docosapentaenoic acid (DPA), an n-3 fatty acid. Of note,
      adding DPA to DHA inhibited DHA-induced differentiation. The differential effects
      of EPA and DHA on preadipocyte differentiation may be due, in part, to
      differences in their intracellular modification which could impact the type of n
      3 fatty acids incorporated into the cells. 

PMID- 24332316
TI  - Complex of 2-(methylthio)aniline with palladium(II) as an efficient catalyst for
      Suzuki-Miyaura C-C coupling in eco-friendly water.
AB  - 2-(Methylthio)aniline (L1), a bidentate (S,N) ligand synthesized by the reaction
      of o-aminothiophenol with methyl iodide, on reacting with Na2PdCl4 in acetone and
      water gives a complex [PdL1Cl2] (1). Single crystal X-ray diffraction studies
      have revealed that the geometry of palladium in 1 is nearly square-planar and the
      ligand L1 is bound to the palladium through S and N in a bidentate coordination
      mode forming a five membered chelate ring. This complex functions as a thermally
      and air stable catalyst of high efficiency for Suzuki-Miyaura CC coupling
      reactions in water. It catalyzes CC coupling between various aryl bromides and
      phenylboronic acid under mild reaction conditions in water. TON value up to
      93,000 has been obtained.

PMID- 24332317
TI  - New functionality of chalcogenide glasses for radiation sensing of nuclear
      wastes.
AB  - Data about gamma radiation induced effects in Ge40Se60 chalcogenide thin films
      and radiation induced silver diffusion within these are presented. Blanket films
      and devices were created to study the structural changes, diffusion products, and
      device performance. Raman spectroscopy, X-ray diffraction, current vs. voltage (I
      V) and impedance measurements expound the behavior of Ge40Se60 glass and silver
      diffusion within this glass under radiation. Raman study shows that there is a
      decrease in the area ratio between edge shared and corner shared structural units
      revealing structural reorganization occurring in the glasses as a result of gamma
      radiation. X-ray diffraction studies revealed that with sufficiently radiation
      dose it is also possible to create Ag2Se in selenium-depleted systems. Oxidation
      of the Ge enriched chalcogenide backbone is confirmed through the electrical
      performance of the sensing elements based on these films. Combination of these
      structural and diffusion products influences the device performance. The I-V
      behavior is characterized by increase in current and then stabilization as a
      function of radiation dose. Additionally, device modeling is also presented using
      Silvaco software and analytical methods to shed light on the device behavior.
      This type of sensor design and material characterizations facilitate in improving
      the radiation sensing capabilities of silver containing chalcogenide glass thin
      films. 

PMID- 24332318
TI  - A horizon scan of global conservation issues for 2014.
AB  - This paper presents the output of our fifth annual horizon-scanning exercise,
      which aims to identify topics that increasingly may affect conservation of
      biological diversity, but have yet to be widely considered. A team of
      professional horizon scanners, researchers, practitioners, and a journalist
      identified 15 topics which were identified via an iterative, Delphi-like process.
      The 15 topics include a carbon market induced financial crash, rapid geographic
      expansion of macroalgal cultivation, genetic control of invasive species,
      probiotic therapy for amphibians, and an emerging snake fungal disease. 

PMID- 24332319
TI  - Meta-analysis of individual patient data from randomized trials of chemotherapy
      plus cetuximab as first-line treatment for advanced non-small cell lung cancer.
AB  - OBJECTIVES: Four randomized phase II/III trials investigated the addition of
      cetuximab to platinum-based, first-line chemotherapy in patients with advanced
      non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the
      benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND
      METHODS: The meta-analysis included individual patient efficacy data from 2018
      patients and individual patient safety data from 1970 patients comprising
      respectively the combined intention-to-treat and safety populations of the four
      trials. The effect of adding cetuximab to chemotherapy was measured by hazard
      ratios (HRs) obtained using a Cox proportional hazards model and odds ratios
      calculated by logistic regression. Survival rates at 1 year were calculated. All
      applied models were stratified by trial. Tests on heterogeneity of treatment
      effects across the trials and sensitivity analyses were performed for all
      endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab
      to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median
      10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs
      4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2%
      vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy
      plus cetuximab in the meta-analysis population was confirmed as manageable.
      Neither trials nor patient subgroups defined by key baseline characteristics
      showed significant heterogeneity for any endpoint. CONCLUSION: The addition of
      cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC
      significantly improved outcome for all efficacy endpoints with an acceptable
      safety profile, indicating a favorable benefit/risk ratio.

PMID- 24332320
TI  - Risk of interstitial lung disease with gefitinib and erlotinib in advanced non
      small cell lung cancer: a systematic review and meta-analysis of clinical trials.
AB  - OBJECTIVES: Gefitinib and erlotinib are oral epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitors (TKIs) widely used in advanced non-small cell
      lung cancer (NSCLC). Interstitial lung disease (ILD) events have been described
      with these agents, although the overall risk remains unclear. We performed a
      systematic review and meta-analysis to determine the incidence and the relative
      risk (RR) associated with the use of gefitinib and erlotinib. MATERIALS AND
      METHODS: PubMed databases were searched for articles published from January 2000
      to October 2012, and abstracts presented at the American Society of Clinical
      Oncology and the European Society of Medical Oncology meetings held between 2000
      and 2012 were searched for relevant studies. Eligible studies included randomized
      controlled trials with gefitinib and erlotinib in advanced NSCLC patients.
      Summary incidence rates, relative risks, and 95% CIs were calculated using fixed
      effects or random-effects models, depending on the heterogeneity of the included
      studies. RESULTS: 15,618 patients from 29 randomized controlled trials were
      selected for this meta-analysis. The overall incidence for all-grade ILD events
      was 1.2% (95% CI, 0.9-1.6%) among patients receiving gefitinib and erlotinib,
      with a mortality of 22.8% (95% CI, 14.6-31.0%). Compared with controls, the RR of
      all-grade ILD events associated with gefitinib and erlotinib was 1.53 (95% CI,
      1.13-2.08; P=0.006) using a fixed-effects model. The RR of fatal ILD events
      associated with EGFR TKIs treatment was 1.96 (95% CI, 1.03-3.72, P=0.041)
      compared with control patients. The analysis was also stratified for drug type,
      study location, treatment arm, and treatment line, but no significant differences
      in RRs were observed. CONCLUSION: Treatment with EGFR TKIs gefitinib and
      erlotinib is associated with a significant increase in the risk of developing
      both all-grade and fatal ILD events in advanced NSCLC.

PMID- 24332321
TI  - Management of thoracolumbar spine fractures.
AB  - BACKGROUND CONTEXT: Traumatic fractures of the spine are most common at the
      thoracolumbar junction and can be a source of great disability. PURPOSE: To
      review the most current information regarding the pathophysiology, injury
      pattern, treatment options, and outcomes. STUDY DESIGN: Literature review.
      METHODS: Relevant articles, textbook chapters, and abstracts covering
      thoracolumbar spine fractures with and without neurologic deficit from 1960 to
      the present were reviewed. RESULTS: The thoracolumbar spine represents a unique
      system from a skeletal as well as neurological standpoint. The rigid rib-bearing
      thoracic spine articulates with the more mobile lumbar spine at the thoracolumbar
      junction (T10 - L2), the site of most fractures. A complete examination includes
      a careful neurologic examination of both motor and sensory systems. CT scans best
      describe bony detail while MRI is most efficient at describing soft tissues and
      neurological structures. The most recent classification system is that of the new
      Thoracolumbar Injury Classification and Severity Score. The different fracture
      types include compression fractures, burst fractures - both stable and unstable 
      , flexion-distraction injuries and fracture dislocations. Their treatment, both
      operative and non-operative depends on the degree of bony compromise,
      neurological involvement, and the integrity of the posterior ligamentous complex.
      Minimally invasive approaches to the care of thoracolumbar injuries have become
      more popular, thus, the evidence regarding their efficacy is presented. Finally,
      the treatment of osteoporotic fractures of the thoracolumbar spine is reviewed,
      including vertebroplasty and kyphoplasty, their risks and controversies, and
      senile burst fractures, as well. CONCLUSIONS: Thoracolumbar spine fractures
      remain a significant source of potential morbidity. Advances in treatment have
      minimized the invasiveness of our surgery and in certain stable situations,
      eliminated it all together.

PMID- 24332322
TI  - Diagnostic tests the NASS stenosis guidelines.

PMID- 24332323
TI  - Re: Diagnostic tests the NASS stenosis guidelines.

PMID- 24332324
TI  - Efficacy of preemptive lornoxicam on postoperative analgesia after surgical
      removal of mandibular third molars.
AB  - OBJECTIVE: Pain is the most encountered complication following third molar
      surgery. Although nonsteroidal anti-inflammatory drugs are often used for pain
      control, the effect of preemptive lornoxicam has not been detailed. We compare
      the analgesic efficacy of preemptive lornoxicam versus postoperative lornoxicam.
      STUDY DESIGN: Forty-three participants aged 18 to 33 years who had bilateral,
      symmetrical third molars were included in this double-blind, randomized, placebo
      controlled study. All participants took part in each of the 2 groups for a 1
      month interval (crossover design). Group Pre received lornoxicam 8 mg
      intravenously 25 minutes before surgery and 2 mL serum saline postoperatively.
      Group Post was given the opposite protocol. Pain was evaluated by visual analog
      scale in the first 12 hours. RESULTS: We observed statistically significant
      differences in the reduction of the pain level in group Pre (P < .05). These
      participants felt less pain in the first 5 postoperative hours and needed fewer
      analgesics in the first 12 postoperative hours. CONCLUSIONS: Preemptive
      lornoxicam is effective for postoperative pain control.

PMID- 24332325
TI  - Malignancy mimicking bisphosphonate-associated osteonecrosis of the jaw: a case
      series and literature review.
AB  - OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaw (BONJ) is a common
      complication of bisphosphonate treatment that has been well documented over the
      past decade. Nevertheless, its pathogenesis is poorly understood, and treatment
      guidelines are based mostly on expert recommendations. Clinicians must be aware
      of malignancy mimicking BONJ, of which a few cases have been documented in the
      literature. STUDY DESIGN: Three patients undergoing long-term treatment with
      intravenous bisphosphonates for malignant disease demonstrated the distinct
      diagnostic signs of BONJ. Surgical treatment was performed by resecting the
      affected bone. In all cases, histologic specimens were taken for analysis.
      RESULTS: Histologic analysis of the bone specimen with surrounding soft tissue
      revealed necrotic bone with signs of inflammation, but also with cells of the
      underlying malignant disease. CONCLUSIONS: Clinical and radiographic diagnosis of
      BONJ should be confirmed by histologic analysis in patients with underlying
      malignant disease.

PMID- 24332326
TI  - Modified versus classic alar base sutures after LeFort I osteotomy: a systematic
      review.
AB  - OBJECTIVE: The purpose of this systematic review is to evaluate the efficacy of a
      new modified alar base cinch suture by comparing it with the commonly used
      classic alar base suture after LeFort I osteotomy. STUDY DESIGN: A comprehensive
      search strategy was performed to include interventional studies involving the
      comparisons of alar base suturing methods after LeFort I osteotomy. Data analyses
      were conducted using the random-effects model. RESULTS: Three studies with 146
      participants undergoing LeFort I maxillary osteotomy were included in this
      review. The results showed that, compared with the classic method, both modified
      transseptal alar base suture and modified reinsertion sutures significantly
      decreased postoperative alar and alar base widening. CONCLUSIONS: The modified
      alar base cinch suture was more effective than the classic alar base suture in
      maintaining preoperative alar and alar base width after LeFort I osteotomy.

PMID- 24332327
TI  - Association between glycemic status and oral Candida carriage in patients with
      prediabetes.
AB  - OBJECTIVE: This study assessed the association between glycemic status and oral
      Candida carriage among patients with prediabetes. STUDY DESIGN: This was a
      comparative study of oral Candida carriage among individuals with prediabetes.
      Oral yeast samples were collected from 150 individuals: group A was 43 patients
      with prediabetes (fasting blood glucose levels and hemoglobin A1c, 100 to 125
      mg/dL and >=5%, respectively); group B was 37 individuals previously considered
      prediabetic but having fasting blood glucose levels <100 mg/dL and hemoglobin A1c
      <5%; and group C was 70 medically healthy individuals. Oral yeasts were
      identified using standard techniques. Unstimulated whole salivary flow rate and
      number of missing teeth were recorded. RESULTS: Oral Candida was isolated from
      100% of patients with prediabetes and from 65.7% of control participants. Candida
      albicans carriage was higher among patients with prediabetes (48.7%) (P < .01)
      and patients in group A (51.2%) (P < .01) than among controls (25.7%). Candida
      carriage, unstimulated whole salivary flow rate, and number of missing teeth were
      similar in groups A and B. CONCLUSIONS: Oral Candida carriage was higher in
      patients with prediabetes than in controls and was independent of glycemic status
      in patients with prediabetes.

PMID- 24332328
TI  - Cost analysis of dental services needed before hematopoietic cell
      transplantation.
AB  - OBJECTIVE: Streptococcal bacteremia occurs during hematopoietic cell
      transplantation (HCT), and treatment of active oral disease may reduce this risk.
      The objective of this study was to determine the type, number, and costs of pre
      transplantation dental procedures in this population. STUDY DESIGN: Data were
      collected retrospectively from the records of patients who were to undergo HCT.
      The type, number, and costs of dental procedures were determined based on median
      charges of MassHealth (the Medicaid program in Massachusetts) and also on the
      median "usual and customary" fees charged by dentists in Massachusetts. RESULTS:
      A total of 405 patients were evaluated. There were 243 men (60%) and 162 women,
      with a median age of 53 years. The median and average costs (in US dollars) of
      dental treatment before HCT were $275 and $384, respectively, for patients
      covered by MassHealth and $368 and $522, respectively, for those with private
      insurance, adjusted to 2012 levels. CONCLUSIONS: Dental evaluation before HCT is
      an economical way for patients to minimize the risk of localized infection and
      possibly reduce the risk of bacteremia that may prolong the length of
      hospitalization.

PMID- 24332329
TI  - Prevalence of calcified carotid artery atheromas in panoramic radiographs of HIV
      positive patients undergoing antiretroviral treatment: a retrospective study.
AB  - OBJECTIVE: This study investigated the prevalence of calcified carotid artery
      atheromas (CCAAs) in panoramic radiographs of HIV-positive patients. STUDY
      DESIGN: A retrospective cross-sectional study was performed to evaluate the
      presence of CCAA in 300 panoramic radiographs. Qualitative variables were
      compared using the chi(2) test or Fisher exact test, as needed. The Mann-Whitney
      or Student t test was used for the quantitative variables. RESULTS: In the
      studied group, 8.2% presented CCAA. Among these patients, most used
      lopinavir/ritonavir (P = .0459), had a greater mean age (P = .0081), and
      displayed a lower nadir CD4 (P = .0195). The use of lopinavir/ritonavir increased
      the chances of CCAA by approximately 2.8-fold compared with those who did not use
      medication (odds ratio, 2.79; 95% confidence interval, 1.12-6.95; P = .045).
      CONCLUSIONS: The variables that were associated with the identification of CCAA
      are compatible with the known atherogenic risk factors in patients with HIV.

PMID- 24332330
TI  - Clinical oral and salivary parameters of children with juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To evaluate clinical oral and salivary parameters of individuals with
      juvenile idiopathic arthritis (JIA). STUDY DESIGN: Clinical parameters and whole
      saliva were collected from children aged 6 to 12 years with JIA (n = 36) and from
      a healthy, matched control group (n = 36). The clinical and salivary parameters
      evaluated were the dental caries (decayed, missing, or filled teeth), gingival
      and simplified oral hygiene indices, salivary flow rate, pH, buffer capacity,
      total protein, and secretory immunoglobulin A concentrations. RESULTS: JIA
      individuals presented poorer oral hygiene (P <= .05) but no difference in the
      dental caries and gingival indices. JIA patients presented an increase in total
      protein concentration (86%) and buffer capacity in the range of pH 6.9 to 6.0
      (10%) and a reduction in initial pH (6%), buffer capacity in the range of pH >=
      7.0 (50%), and immunoglobulin A concentration (27%) (P <= .05). CONCLUSIONS: JIA
      is associated with poor oral hygiene and salivary changes, including reductions
      in immune factors and an altered profile of salivary buffer capacity.

PMID- 24332331
TI  - Tissue microarray is a reliable method for immunohistochemical analysis of
      pleomorphic adenoma.
AB  - OBJECTIVE: To determine the most adequate number and size of tissue microarray
      (TMA) cores for pleomorphic adenoma immunohistochemical studies. STUDY DESIGN:
      Eighty-two pleomorphic adenoma cases were distributed in 3 TMA blocks assembled
      in triplicate containing 1.0-, 2.0-, and 3.0-mm cores. Immunohistochemical
      analysis against cytokeratin 7, Ki67, p63, and CD34 were performed and
      subsequently evaluated with PixelCount, nuclear, and microvessel software
      applications. RESULTS: The 1.0-mm TMA presented lower results than 2.0- and 3.0
      mm TMAs versus conventional whole section slides. Possibly because of an
      increased amount of stromal tissue, 3.0-mm cores presented a higher microvessel
      density. Comparing the results obtained with one, two, and three 2.0-mm cores,
      there was no difference between triplicate or duplicate TMAs and a single-core
      TMA. CONCLUSIONS: Considering the possible loss of cylinders during
      immunohistochemical reactions, 2.0-mm TMAs in duplicate are a more reliable
      approach for pleomorphic adenoma immunohistochemical study.

PMID- 24332333
TI  - The spectrum of primary mucosal CD30-positive T-cell lymphoproliferative
      disorders of the head and neck.
AB  - OBJECTIVE: To retrospectively investigate the clinicopathologic spectrum of
      primary mucosal CD30-positive T-cell lymphoproliferative disorders (PTCLDs) of
      the head and neck. STUDY DESIGN: Archives of PTCLDs primarily arising in head and
      neck mucosa were reviewed. Immunostaining of CD20, CD3, CD4, CD8, CD30, CD56,
      anaplastic lymphoma kinase (ALK), epithelial membrane antigen (EMA), cytotoxic
      molecules (TIA-1, granzyme B, or perforin), and Ki67; in situ hybridization for
      Epstein-Barr virus; and T-cell receptor gene rearrangement analysis were
      performed. RESULTS: Fourteen cases of primary mucosal anaplastic large cell
      lymphoma (M-ALCL) were identified, and no lymphomatoid papulosis (LyP) cases were
      found. All cases demonstrated atypical mononuclear neoplastic cells with diverse
      histology and cytomorphology. The typical immunophenotype of neoplastic cells was
      CD3-positive, CD4-positive, CD8-negative, CD30-positive, ALK-negative, and
      cytotoxic molecules-positive. Infiltration of inflammatory cells was common. All
      cases presented an indolent course, regardless of therapy. CONCLUSIONS: PTCLDs of
      the head and neck provisionally included M-ALCL alone.

PMID- 24332332
TI  - Increased expression of the long non-coding RNA UCA1 in tongue squamous cell
      carcinomas: a possible correlation with cancer metastasis.
AB  - OBJECTIVE: The aim of this study was to examine the expression of several cancer
      related long non-coding RNAs (lncRNAs) in patients with tongue squamous cell
      carcinoma (TSCC) and to explore its clinical significance. STUDY DESIGN: A total
      of 94 TSCC tissue specimens and matched adjacent normal tissue specimens were
      collected from patients undergoing surgery for TSCC. Differences in the
      expression of cancer-related lncRNAs were examined via quantitative reverse
      transcriptase polymerase chain reaction. WST-1 assay and transwell migration
      assay were carried out to estimate the proliferation and migration abilities of
      TSCC cells with different expression levels of urothelial cancer-associated 1
      (UCA1) lncRNA. RESULTS: The expression levels of lncRNA UCA1 were significantly
      elevated in TSCC tissues (P < .0001) and were statistically correlated with lymph
      node metastasis (P = .0371). Over-expression of UCA1 lncRNA could promote
      metastatic but not proliferation ability of TSCC cells. CONCLUSIONS: Expression
      of UCA1 lncRNA was enhanced in TSCCs and may play a role in tumor metastasis.

PMID- 24332334
TI  - Granulomatous foreign body reaction to dermal cosmetic fillers with intraoral
      migration.
AB  - OBJECTIVE: We report intraoral granulomatous foreign body reactions in patients
      treated with calcium hydroxylapatite (CHA) or poly-l-lactic acid (PLA). STUDY
      DESIGN: Clinical and histopathologic data were obtained from 25 patients who
      developed orofacial nodules or swelling after dermal filler injections. RESULTS:
      All 25 patients were women aged 35 to 78 years (median, 55 years). All had a
      history of injection of CHA (n = 13) or PLA (n = 12) to the lips, nasolabial
      area, or mental area. Two patients developed cutaneous nodules at the sites of
      injections; all others presented with intraoral nodules (labial/buccal or
      vestibular mucosa) distant from the site of injections, suggestive of filler
      migration. Five of 21 cases presented with pain. Histopathologically, CHA
      presented as a diffuse mass of mauve-gray or beige, nonrefractile spherules, and
      PLA as rice- or spindle-shaped, geometric, refractile bodies within circumscribed
      nodules. CONCLUSIONS: Cutaneous injections of CHA and PLA fillers may induce
      granulomatous reactions presenting as intraoral nodules distant from the
      injection sites.

PMID- 24332335
TI  - Agreement between cone beam computed tomography images and panoramic radiographs
      for initial orthodontic evaluation.
AB  - OBJECTIVE: The aim of this study was to compare the agreement between cone beam
      computed tomography (CBCT) and panoramic radiographs for initial orthodontic
      evaluation. This study was not meant to test differences between imaging
      modalities or to indicate superiority of one technique. STUDY DESIGN: Thirty
      eight subjects with both panoramic and CBCT images were retrospectively
      collected. Eight observers answered 14 observational questions. The observation
      was repeated after 4 weeks. RESULTS: CBCT images yielded better agreement between
      2 observer groups (orthodontic residents and radiologists) and better inter- and
      intraobserver agreement. The agreement between panoramic radiographs and CBCT
      scans was moderate. CONCLUSIONS: If CBCT is a priori present in a case with
      justified indications, it has the potential to provide valuable diagnostic
      information for initial orthodontic evaluation and extra information for
      treatment planning. The moderate agreement between panoramic and CBCT images may
      indicate that the nature and amount of information gained from both imaging
      sources is deviant.

PMID- 24332336
TI  - Essential mixed cryoglobulinemia manifesting as recurrent perioral edema: report
      of a case.
AB  - Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures <37
      degrees C but that redissolve if heated; they are broadly divided into 3 classes.
      Cryoglobulinemia has a plethora of clinical manifestations, but it typically
      presents a vasculitic syndrome, most notably a triad of purpura, arthralgia, and
      weakness secondary to cryoglobulin deposition in small or medium-sized blood
      vessels. The highly variable clinical presentation and inconsistent laboratory
      isolation of cryoglobulins mean that the diagnosis may be one of exclusion or of
      retrospective review. We describe a case of a 67-year-old woman whose principal
      symptom was recurrent perioral edema, which was characteristically induced by
      cold. Raised cryoglobulins combined with a positive autoantibody screen suggested
      mixed cryoglobulinemia secondary to Sjogren syndrome. However, in the subsequent
      6 years, she has remained generally well, having developed no autoimmune,
      neoplastic, or other disease, suggesting the diagnosis is one of "essential"
      mixed cryoglobulinemia. No treatment other than symptomatic analgesia has been
      required. 

PMID- 24332337
TI  - Measurement of 226Ra in soil from oil field: advantages of gamma-ray spectrometry
      and application to the IAEA-448 CRM.
AB  - The analytical performance of gamma-ray spectrometry for the measurement of
      (226)Ra in TENORM (Technically Enhanced Naturally Occurring Radioactive Material)
      soil was investigated by the IAEA. Fast results were obtained for
      characterization and certification of a new TENORM Certified Reference Material
      (CRM), identified as IAEA-448 (soil from oil field). The combined standard
      uncertainty of the gamma-ray spectrometry results is of the order of 2-3% for
      massic activity measurement values ranging from 16500 Bq kg(-1) to 21500 Bq kg(
      1). Methodologies used for the production and certification of the IAEA-448 CRM
      are presented. Analytical results were confirmed by alpha spectrometry. The "t"
      test showed agreement between alpha and gamma results at 95% confidence level.

PMID- 24332338
TI  - A dedicated LIMS for routine gamma-ray spectrometry.
AB  - We developed a Microsoft((r)) Access-based LIMS (Laboratory Information and
      Management Systems), gamma-LIMS, for the management of our gamma-spectrometry
      laboratory, in which thousands of routine, but high-quality analyses are
      performed each year. This paper explains the main features of the gamma-LIMS and
      puts special attention on the interfacing methods and solutions for using the
      GenieTM2000 spectrometry software in conjunction with the EFFTRAN package, which
      serves for efficiency transfer calculations, coincidence summing corrections and
      a procedure for uncertainty estimation. 

PMID- 24332339
TI  - Standardization of Tc-99 by three liquid scintillation counting methods.
AB  - The NMISA participated in the international key comparison of the pure beta
      emitter Technetium-99, CCRI(II)-K2.Tc-99. The comparison solution was
      standardized using three methods, namely the TDCR efficiency calculation method,
      the CIEMAT/NIST efficiency tracing method and the 4pi(LS)beta-gamma coincidence
      tracing method with Co-60 as tracer. Excellent agreement between results obtained
      with the three methods confirmed the applicability of the beta spectral shape
      given by the latest (2011) DDEP evaluation of Tc-99 decay data, rather than the
      earlier (2004) evaluation. 

PMID- 24332340
TI  - Standardisation of 64Cu using a software coincidence counting system.
AB  - The activity of the radionuclide (64)Cu was determined by the efficiency
      extrapolation method applied to 4pi(PC)-gamma coincidence counting. The
      standardisation was performed by software coincidence counting-a digital method
      for primary activity measurement that simplifies the setting of optimal
      coincidence parameters. The gamma-ray-energy window, characterised by identical
      gamma detection efficiency related to the sum of EC and to the sum of beta decay
      branches, was found. This setting ensured a linear and zero slope extrapolation
      curve. 

PMID- 24332341
TI  - Improved method for the assessment of 60Co and 134Cs point sources in samples
      with non-homogeneous matrix.
AB  - The correlation method (Suvaila et al., 2013) is extended to the assessment of
      (60)Co and (134)Cs point sources embedded in non-homogeneous samples.
      Experimental data reveal a strong correlation between the efficiency epsilon(1173
      keV) and the ratio of the count rate R in the sum peak of 2505 keV and in the
      peak of 1332 keV. The correlation pattern and the measured R(2505)/R(1332) give
      unbiased values for epsilon(1173 keV), independent of source position and sample
      matrix. Monte Carlo simulations for (60)Co and (134)Cs support this conclusion.

PMID- 24332342
TI  - Development of a calibration methodology for large-volume, solid 68Ge phantoms
      for traceable measurements in positron emission tomography.
AB  - We have developed a methodology to calibrate the (68)Ge activity concentration in
      large (9L) cylindrical epoxy phantoms in a way that is traceable to national
      standards. The method was tested on two prototype cylindrical phantoms that are
      being used in a clinical trial and gave (68)Ge activity concentration values with
      combined standard uncertainties of about 1.1%. Imaging data from the phantoms
      using a calibrated PET-CT scanner gave values consistent with the calibrated
      activity concentrations within experimental uncertainties. 

PMID- 24332343
TI  - Equivalence of computer codes for calculation of coincidence summing correction
      factors.
AB  - The aim of the study was to check for equivalence of computer codes that can
      perform calculations of true coincidence summing correction factors. All
      calculations were performed for a set of well-defined detector and sample
      parameters, without any reference to empirical data. For a p-type detector model
      the application of different codes resulted in satisfactory agreement in the
      calculated correction factors. For high-efficiency geometries in combination with
      an n-type detector and a radionuclide emitting abundant X-rays the results were
      scattered. 

PMID- 24332344
TI  - Investigation of cosmic-ray muon induced processes by the MIREDO facility.
AB  - The MIREDO (Muon Induced Rare Event Dynamic Observatory) spectrometer system is
      primarily developed for the study of cosmic muon induced processes in different
      materials. Exploration of such interactions can be important for ultra-low
      background experiments. The system is based on the 100% relative efficiency ultra
      low-background HPGe spectrometer. With the addition of two plastic scintillators
      and a fast-slow coincidence circuit, the coincidence events between the plastic
      detectors and the HPGe spectrometer have been investigated. First results derived
      for a CaO powder sample, placed in a Marinelli beaker, are presented and
      discussed. 

PMID- 24332345
TI  - Evaluation of three electrodeposition procedures for uranium, plutonium and
      americium.
AB  - While both mass spectrometry and alpha-particle spectrometry have been widely
      used for measuring alpha activities, the former is preferred since many
      laboratories are not equipped with ICP-MS and MC-ICP-MS systems. In this study,
      three electrodeposition techniques using ammonium chloride, ammonium oxalate and
      ammonium sulphate as electrolyte solutions were applied and evaluated for the
      preparation of uranium, plutonium and americium sources for alpha-particle
      spectrometry. Changes in pH and temperature throughout the electrodeposition
      process were measured every 15 min, together with percentage deposition every 30
      min. The percentage deposition in each method was checked at 300, 400 and 500 mA,
      and the optimised time and current were determined.

PMID- 24332346
TI  - Times, they are a-changing.

PMID- 24332347
TI  - Reply to Jerome Verine, Christophe Leboeuf and Philippe Ratajczak's letter to the
      editor re: Jimsgene Sanjmyatav, Sven Hauke, Mieczyslaw Gajda, et al.
      Establishment of a multicolour fluorescence in situ hybridisation-based assay for
      subtyping of renal cell tumours. Eur Urol 2013;64:689-91.

PMID- 24332348
TI  - Improving outcome of surgical procedures is not possible without adequate quality
      measurement.
AB  - Outcome measurement allows for acknowledging differences in quality and must be
      used as a basis for quality assessment, regardless of what procedure is to be
      assessed and improved. As urologists, we should actively take the lead to guide
      this necessary and inevitable process. 

PMID- 24332349
TI  - Assessment of the thermodynamic properties of poly(2,2,2-trifluoroethyl
      methacrylate) by inverse gas chromatography.
AB  - The thermodynamic properties of poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA)
      were determined by the aid of the inverse gas chromatography technique (IGC), at
      infinite dilution. The interactions between the polymer and 15 solvents were
      examined in the temperature range of 120-150  degrees C via the estimation of the
      thermodynamic sorption parameters, the parameters of mixing at infinite dilution,
      the weight fraction activity coefficients and the Flory-Huggins interaction
      parameters. Additionally, the total and the partial solubility parameters of
      PTFEMA were estimated. The findings of this work indicate that the type and
      strength of the intermolecular interactions between the polymer and the solvents
      are strongly depended on the functional groups of the polymer and the solvents.
      The proton acceptor character of the polymer is responsible for the preferential
      solubility of PTFEMA in chloroform which acts as a proton donor solvent. The
      results also reveal that the polymer is insoluble in alkanes and alcohols whereas
      it presents good miscibility with polar solvents, especially with 2-butanone, 2
      pentanone and 1,4-dioxane. Furthermore, the total and dispersive solubility
      parameters appear diminishing upon temperature rise, whereas the opposite
      behavior is noticed for the polar and hydrogen bonding solubility parameters. The
      latter increase with temperature, probably, due to conformational changes of the
      polymer on the solid support. Finally, comparison of the solubilization profiles
      of fluorinated methacrylic polymers studied by IGC, leads to the conclusion that
      PTFEMA is more soluble compared to polymers with higher fluorine content.

PMID- 24332350
TI  - Graphenized pencil lead fiber: facile preparation and application in solid-phase
      microextraction.
AB  - Graphenized pencil lead fiber was facilely prepared by in situ chemical
      exfoliation of graphite in pencil lead fiber to few-layered graphene sheets via a
      one-pot, one-step pressurized oxidation reaction for the first time. This new
      fiber was characterized and demonstrated to be a highly efficient but low-cost
      solid-phase microextraction (SPME) fiber. The extraction performance of the fiber
      was evaluated with four bisphenol analogs [bisphenol A (BPA), bisphenol S (BPS),
      bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA)] as model analytes in
      direct SPME mode. Unlike commercially available fibers, the graphenized pencil
      lead fiber showed an excellent chemical stability in highly saline, acidic,
      alkaline and organic conditions due to its coating-free configuration. The fiber
      also showed a very long lifespan. Furthermore, high extraction efficiency and
      good selectivity for the analytes with a wide polarity range could be obtained
      due to the exceptional properties of graphene. The detection limits (LODs) for
      the analytes were in the range of 1.1-25ng/L. The fiber was successfully applied
      in the analysis of tap water and effluent samples from a waste water treatment
      plant with spike recoveries ranging from 68.5 to 105.1%. Therefore, the
      graphenized pencil lead fiber provides a high performance, cheap, robust, and
      reliable tool for SPME. 

PMID- 24332351
TI  - Impact of a new respiratory amplitude-based gating technique in evaluation of
      upper abdominal PET lesions.
AB  - PET acquisition requires several minutes which can lead to respiratory motion
      blurring, to increase partial volume effect and SUV under-estimation. To avoid
      these artifacts, conventional 10-min phase-based respiratory gating (PBRG) can be
      performed but is time-consuming and difficult with a non-compliant patient. We
      evaluated an automatic amplitude-based gating method (AABG) which keeps 35% of
      the counts at the end of expiration to minimize respiratory motion. We estimated
      the impact of AABG on upper abdominal lesion detectability, quantification and
      patient management. METHODS: We consecutively included 31 patients (82 hepatic
      and 25 perihepatic known lesions). Each patient underwent 3 acquisitions on a
      Siemens Biograph mCT (4 rings and time-of-flight): a standard free-breathing
      whole-body (SWB, 5-7 steps/2.5 min per step, 3.3+/-0.4 MBq/kg of 18F-FDG), a 10
      min PBRG with six bins and a 5-min AABG method. All gated acquisitions were
      performed with an ANZAI respiratory gating system. SUVmax and target to
      background ratio (TBR, defined as the maximum SUV of the lesion divided by the
      mean SUV of a region of interest drawn in healthy liver) were compared. RESULTS:
      All 94 lesions in SWB images were detected in the gated images. 10-min PBRG and 5
      min AABG acquisitions respectively revealed 9 and 13 new lesions and relocated 7
      and 8 lesions. Four lesions revealed by 5-min AABG were missed by 10-min PBRG in
      3 non-compliant patients. Both gated methods failed to relocate 2 lesions seen on
      SWB acquisition. Compared to SWB, TBR increased significantly with 10-min PBRG
      and with 5-min AABG (respectively 41+/-59%, p=4.10-3 and 66+/-75%, p=6.10-5)
      whereas SUVmax did not (respectively 14+/-43%, p=0.29 with 10-min PBRG, and 24+/
      46%, p=0.11 with 5-min AABG). CONCLUSION: The AABG is a fast and a user-friendly
      respiratory gating method to increase detectability and quantification of upper
      abdominal lesions compared to the conventional PBRG procedure and the SWB
      acquisition.

PMID- 24332352
TI  - Low concentration contrast medium for dual-source computed tomography coronary
      angiography by a combination of iterative reconstruction and low-tube-voltage
      technique: feasibility study.
AB  - OBJECTIVES: To assess the impact of low-concentration contrast medium on vascular
      enhancement, image quality and radiation dose of coronary CT angiography (cCTA)
      by using a combination of iterative reconstruction (IR) and low-tube-voltage
      technique. MATERIALS AND METHODS: One hundred patients were prospectively
      randomized to two types of contrast medium and underwent prospective
      electrocardiogram-triggering cCTA (Definition Flash, Siemens Healthcare;
      collimation: 128 mm * 0.6mm; tube current: 300 mAs). Fifty patients received
      Iopromide 370 were scanned using the conventional tube setting (100 kVp or 120
      kVp if BMI >= 25 kg/m(2)) and reconstructed with filtered back projection (FBP).
      Fifty patients received Iodixanol 270 were scanned using the low-tube-voltage (80
      kVp or 100 kVp if BMI >= 25 kg/m(2)) technique and reconstructed with IR. CT
      attenuation was measured in coronary artery and other anatomical regions. Noise,
      image quality and radiation dose were compared. RESULTS: Compared with two
      Iopromide 370 subgroups, Iomeprol 270 subgroups showed no significant difference
      in CT attenuation (576.63 +/- 95.50 vs. 569.51 +/- 118.93 for BMI< 25 kg/m(2),
      p=0.647 and 394.19 +/- 68.09 vs. 383.72 +/- 63.11 for BMI >= 25 kg/m(2),
      p=0.212), noise (in various anatomical regions of interest) and image quality
      (3.5 vs. 4.0, p=0.13), but significantly (0.41 +/- 0.17 vs. 0.94 +/- 0.45 for
      BMI< 25 kg/m(2), p<0.001 and 1.14 +/- 0.24 vs. 2.37 +/- 0.69 for BMI >= 25
      kg/m(2), p<0.001) lower radiation dose, which reflects dose saving of 56.4% and
      51.9%, respectively. CONCLUSIONS: Combined IR with low-tube-voltage technique, a
      low-concentration contrast medium of 270 mg I/ml can still maintain the contrast
      enhancement without impairing image quality, as well as significantly lower the
      radiation dose.

PMID- 24332353
TI  - Preoperative MR-guided wire localization for suspicious breast lesions:
      comparison of manual and automated software calculated targeting.
AB  - OBJECTIVES: Preoperative magnetic resonance (MR) guided wire localization is a
      frequently used tool to target MR-only visible breast lesions. Different
      techniques are available. Targeting can be performed using automated software or
      a manual approach. Aim of this study therefore was to compare manually and
      automated software assisted wire localization of suspicious breast lesions
      regarding to image time and accurate positioning. METHODS: 60 females with
      suspicious breast lesions underwent MR-guided wire localization. In 30 patients a
      manual target calculation and in another 30 patients a software calculated
      approach was used. Time measurements for MR imaging as well as calculation of the
      target coordinates were performed. Furthermore size measurements of (i) lesions,
      (ii) distance to wire anchor as well as, (iii) distance to skin were performed. A
      Mann-Whitney-test was used for statistical evaluation. RESULTS: Total imaging
      time was shorter for the automated software calculated approach but failed to
      show a statistical significant difference (p=0.13). Time for localization of the
      lesions was significantly shorter for the software based method (p<0.001). Lesion
      sizes, distances to wire anchor and skin showed no statistically significant
      differences. CONCLUSIONS: Preoperative MR-guided wire localization of suspicious
      lesions that are accessible horizontally, a manually or automated software
      generated target calculation can be used. As MR guided wire localization of
      breast lesions needs its time in total, a minimal time consuming approach and
      therefore an automated software calculated targeting (if available) should be
      preferred.

PMID- 24332354
TI  - CMR assessment after a transapical-transcatheter aortic valve implantation.
AB  - AIMS: To describe the time course of myocardial scarring after transapical
      transcatheter aortic valve implantation (TA-TAVI) with the Edwards SAPIEN XTTM
      and the Edwards SAPIENTM prosthesis in a 3-month follow-up study using cardiac
      magnetic resonance imaging (CMR). METHODS: In 20 TA-TAVI patients, CMR was
      performed at discharge and 3 months (3M). Cine-MRI was used for left ventricular
      (LV) functional assessment, and late gadolinium enhancement (LGE) imaging was
      employed for detecting the presence of myocardial scarring. Special attention was
      given to any artifacts caused by the prosthesis, which were consequently defined
      using a three-grade artifact scale. RESULTS: We systematically reported the
      presence of small LGE hyperintensity relating to the apical segment, with no
      variation found between discharge and 3M (2.8+/-1.6g vs. 2.35+/-1.1g). LV
      ejection fraction, end-diastolic, and end-systolic volumes did not significantly
      vary. A small area of apical akinesia was observed, with no improvement at follow
      up. Whereas the Edwards SAPIEN XTTM prosthesis and the Edwards SAPIENTM
      prosthesis are both constituted by metallic stenting structure, the Edwards
      SAPIENTM was responsible for a larger signal void, thus potentially limiting the
      diagnostic performance of CMR. CONCLUSIONS: CMR may be performed safely in the
      context of TA-TAVI. The presence of a very small apical infarction correlating
      with focal akinesia was observed. As expected, the Edwards SAPIEN XTTM prosthesis
      was shown to be particularly suitable for CMR assessment.

PMID- 24332355
TI  - Pilot clinical trial on the efficacy of prophylactic use of vitamin K1-based
      cream (Vigorskin) to prevent cetuximab-induced skin rash in patients with
      metastatic colorectal cancer.
AB  - BACKGROUND: Cetuximab is an effective option for the treatment of metastatic
      colorectal cancer in the first and subsequent lines of treatment; among its side
      effects, acneiform skin rash is one of the major causes of treatment delay,
      reduction, or interruption, with a negative effect on quality of life. No
      effective strategy to prevent skin rash induced by epidermal growth factor
      receptor inhibitors is available; however, encouraging results have come from
      vitamin K1, phytomenadione, applied as a topical formulation. Available studies
      have been conducted in heterogeneous populations and are mainly focused on the
      use of vitamin K1-based cream for the treatment, rather than the prophylaxis, of
      acneiform rash. PATIENTS AND METHODS: Forty-one consecutive patients from a
      single center all affected by metastatic colorectal cancer and receiving
      cetuximab, alone or combined with chemotherapy, applied vitamin K1-based cream to
      prevent the occurrence of acneiform skin rash. The cream was applied twice a day
      on the face and trunk from the first day of administration of cetuximab. RESULTS:
      The application of the cream was well tolerated. No grade 4 rash was reported.
      The proportion of grade 3 skin rash in the first 8 weeks of treatment in this
      population was 15%, at the lower limit of values reported in the literature, and
      the proportion of patients with grade 2 rash was reduced (22.5%). CONCLUSION:
      This experience confirms available data in a homogeneous population, suggesting a
      possible benefit of topical vitamin K1 as prophylaxis for cetuximab-induced skin
      rash in patients with metastatic colorectal cancer.

PMID- 24332356
TI  - A pilot study assessing the incidence and clinical significance of circulating
      tumor cells in esophagogastric cancers.
AB  - BACKGROUND: Circulating tumor cells (CTCs) have been found to be of clinical
      utility in predicting response to treatment and prognosis in several
      malignancies. Less is known of the prevalence and clinical relevance of CTCs in
      esophagogastric adenocarcinoma, with the available data arising from
      heterogeneous patient populations using varied detection methods. PATIENTS AND
      METHODS: A pilot study was undertaken to assess the prevalence of CTCs in
      patients with advanced esophageal or gastric adenocarcinoma. Patients were
      eligible if they had advanced disease and either had received no prior therapy or
      had progressed after prior chemotherapy. Blood samples for CTC analysis were
      obtained at baseline and during the course of treatment. The CellSearch
      immunomagnetic CTC detection platform was used. RESULTS: Twenty-two patients with
      metastatic esophageal or gastric adenocarcinoma were enrolled. Eighteen received
      first-line EOX (epirubicin/oxaliplatin/capecitabine) chemotherapy (+/-
      panitumumab) and had baseline samples suitable for CTC analysis. At baseline, >=
      2 CTCs were detected in 8 patients (44%). Overall tumor response rate was 60% in
      patients with < 2 CTCs and 37.5% in patients with >= 2 CTCs. Median progression
      free and overall survival were 6.1 and 10.5 months and 5.2 and 6.1 months in the
      groups of patients with < 2 CTCs and >= 2 CTCs, respectively. The study was
      prematurely discontinued, owing to the withdrawal of commercial support.
      CONCLUSION: The incidence of CTCs in locally advanced or metastatic
      esophagogastric cancer may be clinically relevant. Investigation of the potential
      clinical utility of CTCs is warranted in a larger cohort of patients with
      esophagogastric cancer.

PMID- 24332357
TI  - Changes in right ventricular free wall strain in patients with coronary artery
      disease involving the right coronary artery.
AB  - BACKGROUND: Chronic ischemia related occult systolic dysfunction of the right
      ventricle is difficult to detect using traditional echocardiography. The aim of
      this study was to verify the diagnostic value of speckle-tracking
      echocardiography in proximal right coronary artery (pRCA) lesion-induced right
      ventricular (RV) occult dysfunction. METHODS: One hundred forty-two patients
      undergoing elective coronary angiography for suspected coronary artery disease
      were divided into two groups according to involvement of the right coronary
      artery. In further analysis, significant stenosis before the acute marginal
      branch was defined as pRCA involvement and compared with a control group. Global
      longitudinal strain and RV free wall longitudinal train (RVLS-FW) were measured
      using speckle-tracking echocardiography. Other traditional parameters to evaluate
      RV function were also measured. RESULTS: Eighty-seven patients in the right
      coronary artery group (61.2%) displayed significant decreases in the magnitudes
      of both global longitudinal strain (-13.65 +/- 3.83% vs -15.69 +/- 4.37%, P =
      .04) and RVLS-FW (-16.04 +/- 5.4% vs -21.18 +/- 4.6%, P = .04), independent of
      other parameters. Conversely, when focusing on pRCA involvement, only RVLS-FW
      showed significant attenuation in the group with pRCA involvement (-14.26 +/-
      4.32% vs -19.96 +/- 4.8%, P = .001). On multivariate analysis, RVLS-FW was still
      independently lower in the group with pRCA involvement (odds ratio, 1.07; 95%
      confidence interval, 1.01-1.14; P = .02). CONCLUSIONS: The results of this study
      show that RVLS-FW was independently impaired in patients with coronary artery
      disease with right coronary artery stenosis, especially with involvement of the
      acute marginal branches. RV strain can be used to detect occult RV dysfunction in
      patients with stable coronary artery disease.

PMID- 24332359
TI  - Unusual presentation of an intraocular foreign body retained for sixty years.
AB  - Intraocular foreign bodies may remain quiescent for many years particularly if
      they are not metallic. We report a case of a missed intraocular stone foreign
      body that had remained asymptomatic underneath the iris for 60 years and appeared
      during cataract surgery. 

PMID- 24332358
TI  - A unique method of retaining orbital prosthesis with attachment systems - a
      clinical report.
AB  - Diminution of the orbital contents post-surgical removal of a malignant tumor can
      have a severe psychological impact on the patient in terms of function and
      esthetics. Therefore, esthetic remedy should be planned subsequently, since tumor
      obliteration precedes cosmetic concern. A convenient option for successful
      rehabilitation in such patients is a simple, user-friendly, removable orbital
      prosthesis. Retention of the prosthesis is one of the key factors for the
      successful rehabilitation. Spectacle frame, conformers, adhesives,
      osseointegrated implants, magnets or buttons have been used to impart retention
      to the prosthesis. The use of semi precision attachments in maxillofacial
      prostheses is limited to the osseointegrated prostheses. This case report
      describes a conventional spectacle frame technique, to retain the silicone
      orbital prosthesis using two different types of stud attachments viz., dalla bona
      and O-ring attachment systems. 

PMID- 24332360
TI  - Fluorescein staining and physiological state of corneal epithelial cells.
AB  - PURPOSE: To evaluate the physiological status of corneal epithelial cells
      exhibiting fluorescein staining. METHODS: Fluorescein staining properties of
      corneal epithelial cells under normal and stressed conditions were studied using
      cell-culture (human corneal limbal epithelial cells - HCLE) and organ-culture
      (rabbit) models. Stress stimuli comprised exposure to hypotonicity,
      hypertonicity, preservatives, scratch, and alkaline wounding. In addition to
      fluorescein, cells were stained with Hoechst-33342 (HO), Propidium-iodide (PI),
      and Annexin-V (AN-V) to identify live, dead and apoptotic cells. Clinical-slit
      lamp and fluorescence confocal-microscopic (FCM) observations were performed. FCM
      images were quantified for fluorescence intensity using Image-J software.
      RESULTS: Healthy HCLE cells uniformly took up fluorescein to a moderate degree
      with a mean grey value of 62 +/- 24 (mean +/- SD) on a scale of 0-256 (no unit).
      Fluorescence levels similar to those observed prior to stress were associated
      with healthy cells. Apoptotic cells showed the highest fluorescence (138 +/- 38).
      Dead cells showed minimal fluorescence (23 +/- 7) that was similar to the
      background (20 +/- 11, p>0.05). Observations in whole rabbit eyes were in general
      agreement with these cell culture findings. CONCLUSIONS: The clinical observation
      of corneal staining with fluorescein suggests the presence of epithelial cells
      that are undergoing apoptosis but does not indicate dead cells. Under in vitro or
      ex vivo conditions, healthy cells took up fluorescein at levels that were lower
      than those of apoptotic cells and thus, are not likely to be perceived as
      exhibiting staining during clinical observation. Sodium fluorescein may be
      considered as a probe for apoptotic epithelial cells.

PMID- 24332361
TI  - [Inadvertent epidural infusion of paracetamol].
AB  - A 45-year-old woman was accidentally administered an epidural infusion of
      paracetamol instead of levobupivacaine for postoperative pain therapy during the
      postoperative period of abdominal hysterectomy under general anesthesia combined
      with epidural analgesia. The patient had no neurological symptoms at any time,
      although a slight tendency to arterial hypotension that did not require treatment
      was observed. No rescue analgesia was necessary until 8h after the start of
      epidural infusion. The incidence of these types of errors is probably
      underestimated, although there are several cases reported with various drugs. 

PMID- 24332362
TI  - Toxicity of copper and zinc to Puntius parrah (Day, 1865).
AB  - The toxicities of the trace metals copper and zinc on the fish Puntius parrah
      were assessed based on standard renewal bioassay methods, and the 96 h LC50
      values for copper and zinc were 0.5 mg/L and 9 mg/L, respectively. The zinc and
      copper concentrations in water and sediment were high in a highly industrialized
      area compared with those in non-industrialized zones of the Periyar River. The
      fish exposed to a sublethal concentration of 0.05 mg/L of Cu and 0.9 mg/L of Zn
      showed a higher accumulation of both of the metals in the liver than in the
      kidneys, gills, and muscles. The histological changes induced by copper and zinc
      on the test organism under sublethal concentrations on the 3rd, 7th, 14th, and
      28th -days of exposure were also studied. There was a significant decrease (p <
      0.001) in the erythrocyte count after exposure to sublethal concentrations,
      whereas the hemoglobin, hematocrit, and mean corpuscular hemoglobin
      concentrations were significantly decreased after 28 days of exposure. Effective
      management strategies need to be developed and implemented to protect water
      bodies and aquatic organisms from trace metal pollution and its toxic effects. 

PMID- 24332363
TI  - Frequency of dengue virus infection in blood donors in Sistan and Baluchestan
      province in Iran.
AB  - Risk of dengue virus in the blood supply has been demonstrated in recent studies.
      In this paper, Chabahar in Sistan and Baluchestan province, south east of Iran,
      was selected for studying dengue infection because of its climatic and
      geographical situation in the middle of the transit way between East Asia and
      other countries. The blood samples were taken from volunteer healthy donors who
      were referred to the Chabahar Blood Center for blood donation. The presence of
      dengue virus (DENV) was studied by detecting IgG to DENV by enzyme linked immune
      sorbent assay (ELISA). Reactive ELISA results were confirmed by an immune
      flouorescence assay (IFA). According to the results, some of the healthy donors
      were infected by DENV, which could not been recognized in donor selection.
      Therefore, special attention should be paid to the criteria of donor selection
      and additional screening tests are recommended. 

PMID- 24332364
TI  - A case of congenital Echovirus 11 infection acquired early in pregnancy.
AB  - Enterovirus (EV) maternal infection during pregnancy and its relation to fetal
      developmental pathology are seldomly described. When reported, the main
      manifestations of EV congenital infections are myocarditis or intra-uterine fetal
      demise (IUFD). No information on intrauterine Echovirus 11 infection or the
      effect of transplacental Echovirus 11 infection on development of the fetus has
      been described in literature up to date (excluding late-pregnancy infections). We
      report here a case of an extreme form of pulmonary hypoplasia in a neonate,
      characterized by total failure of development of terminal respiratory units. This
      pregnancy was marked by spontaneous demise of a co-twin at 14 weeks of gestation
      (WG), as well as by positive PCR for EV (Echovirus 11 serotype) in the amniotic
      fluid, performed for moderate pericardial effusion at 22WG. No signs of cardiac
      disease were further observed, but at 32WG a bilateral abnormal lung development
      was noticed After spontaneous delivery at 38WG, the child could not be
      resuscitated, and died at one hour after birth. Pulmonary hypoplasia is usually
      described following decrease intrapulmonary pressure due to oligohydramnios or
      compression due to intrathoracic mass of variable cause. However, rare cases of
      primary pulmonary hypoplasia are also described and usually of unknown etiology.
      The coexistence in our case of a congenital EV infection and a severe primary
      pulmonary hypoplasia with congenital acinar aplasia, challenges our understanding
      of the pathogenesis of this severe pulmonary growth arrest. 

PMID- 24332365
TI  - Real-time tracking of neighborhood surroundings and mood in urban drug misusers:
      application of a new method to study behavior in its geographical context.
AB  - BACKGROUND: Maladaptive behaviors may be more fully understood and efficiently
      prevented by ambulatory tools that assess people's ongoing experience in the
      context of their environment. METHODS: To demonstrate new field-deployable
      methods for assessing mood and behavior as a function of neighborhood
      surroundings (geographical momentary assessment; GMA), we collected time-stamped
      GPS data and ecological momentary assessment (EMA) ratings of mood, stress, and
      drug craving over 16 weeks at randomly prompted times during the waking hours of
      opioid-dependent polydrug users receiving methadone maintenance. Locations of EMA
      entries and participants' travel tracks calculated for the 12 before each EMA
      entry were mapped. Associations between subjective ratings and objective
      environmental ratings were evaluated at the whole neighborhood and 12-h track
      levels. RESULTS: Participants (N=27) were compliant with GMA data collection;
      3711 randomly prompted EMA entries were matched to specific locations. At the
      neighborhood level, physical disorder was negatively correlated with negative
      mood, stress, and heroin and cocaine craving (ps<.0001-.0335); drug activity was
      negatively correlated with stress, heroin and cocaine craving (ps .0009-.0134).
      Similar relationships were found for the environments around respondents' tracks
      in the 12h preceding EMA entries. CONCLUSIONS: The results support the
      feasibility of GMA. The relationships between neighborhood characteristics and
      participants' reports were counterintuitive and counter-hypothesized, and
      challenge some assumptions about how ostensibly stressful environments are
      associated with lived experience and how such environments ultimately impair
      health. GMA methodology may have applications for development of individual- or
      neighborhood-level interventions.

PMID- 24332366
TI  - A neurologist's approach to delirium: diagnosis and management of toxic metabolic
      encephalopathies.
AB  - Toxic metabolic encephalopathies (TMEs) present as an acute derangement in
      consciousness, cognition and behavior, and can be brought about by various
      triggers, including endocrine and metabolic disturbances, exogenous toxins, pain
      and infection. Also referred to as "delirium" or "acute confusional states," TMEs
      are characterized by (1) an altered level of consciousness and activity, (2)
      global changes in cognition with inattention, (3) a fluctuating course with
      disturbances in the sleep-wake cycle, and (4) asterixis and myoclonus. The
      pathophysiology of this syndrome is poorly understood. Imbalanced
      neurotransmitter signaling and pathologically heightened brain inflammatory
      cytokine signaling have been proposed as candidate mechanisms. Focal brain
      lesions can also occasionally mimic TMEs. A neurological examination is required
      to identify the presence of focal findings, which when present, identify a new
      focal lesion or the recrudescence of prior ischemic, inflammatory or neoplastic
      insults. Diagnostic testing must include a search for metabolic and infectious
      derangements. Offending medications should be withdrawn. Magnetic resonance
      imaging, cerebrospinal fluid analysis and electroencephalography should be
      considered in select clinical situations. In addition to being an unpleasant
      experience for the patient and family, this condition is associated with extended
      hospital stays, increased mortality and high costs. In individuals with
      diminished cognitive reserve, episodes of TME lead to an accelerated decline in
      cognitive functioning. Starting with an illustrative case, this paper provides a
      neurologist's approach to the diagnosis, differential diagnosis and management of
      toxic metabolic encephalopathies.

PMID- 24332367
TI  - Cronobacter spp. as emerging causes of healthcare-associated infection.
AB  - BACKGROUND: Until recently, members of the Cronobacter genus (formerly known as
      Enterobacter sakazakii) were a relatively unknown cause of nosocomial infections.
      However, their association with infant infections, particularly through the
      consumption of contaminated reconstituted infant formula in neonatal intensive
      care units, has resulted in international efforts to improve neonatal health
      care. AIM: To investigate current understanding of this emergent group of
      bacterial pathogens and the steps taken to reduce neonatal infection. METHODS: A
      literature review was undertaken to determine current knowledge of the
      Cronobacter genus with respect to recent taxonomic revisions, sources and
      clinical relevance. FINDINGS: The majority of severe neonatal meningitis
      infections are associated with one of the 10 Cronobacter spp., the clonal complex
      known as C. sakazakii sequence type 4. International efforts by the Food and
      Agriculture Organization-World Health Organization (WHO) to reduce the risk of
      neonatal infection by this organism have resulted in improved microbiological
      safety of powdered infant formula (PIF), but revised guidelines for feeding
      practices have been problematic. In addition, the majority of infections occur in
      the adult population and the sources are unknown. CONCLUSION: International
      improvements in the microbiological safety of PIF and advice on feeding practices
      have focused on improving neonatal health care following the heightened awareness
      of Cronobacter infections in this particular age group. These measures are also
      likely to reduce neonatal exposure to other opportunistic bacterial pathogens,
      but a number of unresolved issues remain with respect to the practicalities of
      feeding premature neonates safely while following WHO advice.

PMID- 24332368
TI  - SMN is essential for the biogenesis of U7 small nuclear ribonucleoprotein and 3'
      end formation of histone mRNAs.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a
      deficiency in the survival motor neuron (SMN) protein. SMN mediates the assembly
      of spliceosomal small nuclear ribonucleoproteins (snRNPs) and possibly other
      RNPs. Here, we investigated SMN requirement for the biogenesis and function of U7
      -an snRNP specialized in the 3'-end formation of replication-dependent histone
      mRNAs that normally are not polyadenylated. We show that SMN deficiency impairs
      U7 snRNP assembly and decreases U7 levels in mammalian cells. The SMN-dependent
      U7 reduction affects endonucleolytic cleavage of histone mRNAs leading to
      abnormal accumulation of 3'-extended and polyadenylated transcripts followed by
      downstream changes in histone gene expression. Importantly, SMN deficiency
      induces defects of histone mRNA 3'-end formation in both SMA mice and human
      patients. These findings demonstrate that SMN is essential for U7 biogenesis and
      histone mRNA processing in vivo and identify an additional RNA pathway disrupted
      in SMA.

PMID- 24332369
TI  - TGF-beta-Id1 signaling opposes Twist1 and promotes metastatic colonization via a
      mesenchymal-to-epithelial transition.
AB  - ID genes are required for breast cancer colonization of the lungs, but the
      mechanism remains poorly understood. Here, we show that Id1 expression induces a
      stem-like phenotype in breast cancer cells while retaining epithelial properties,
      contrary to the notion that cancer stem-like properties are inextricably linked
      to the mesenchymal state. During metastatic colonization, Id1 induces a
      mesenchymal-to-epithelial transition (MET), specifically in cells whose
      mesenchymal state is dependent on the Id1 target protein Twist1, but not at the
      primary site, where this state is controlled by the zinc finger protein Snail1.
      Knockdown of Id expression in metastasizing cells prevents MET and dramatically
      reduces lung colonization. Furthermore, Id1 is induced by transforming growth
      factor (TGF)-beta only in cells that have first undergone epithelial-to
      mesenchymal transition (EMT), demonstrating that EMT is a prerequisite for
      subsequent Id1-induced MET during lung colonization. Collectively, these studies
      underscore the importance of Id-mediated phenotypic switching during distinct
      stages of breast cancer metastasis. 

PMID- 24332371
TI  - Intraoperative anterior segment optical coherence tomography: a novel assessment
      tool during deep anterior lamellar keratoplasty.
AB  - PURPOSE: To describe the use of high-resolution anterior segment optical
      coherence tomography (AS-OCT) during deep anterior lamellar keratoplasty (DALK).
      DESIGN: Prospective case series. METHODS: At the Singapore National Eye Centre we
      performed sequential intraoperative AS-OCT scans using iVue 100-2 (Optovue,
      Fremont, CA, USA) during various DALK techniques. RESULTS: In case 1 (corneal
      scarring) the OCT images helped to guide manual dissection, showed the depth of
      the needle track before air injection, and identified the location of a small
      bubble when the big bubble failed. In cases 2 (macular dystrophy) and 3
      (lattice), viscodissection was undertaken, but in case 2 the OCT showed the
      viscoelastic trapped intrastromally, compared to case 3, in which the viscobubble
      dissection was successful. In case 4 (irregular corneal thinning and scarring),
      AS-OCT enabled accurate decision on initial trephination and guided dissection.
      In case 5 (keratoconus), the OCT showed the achieved big-bubble and detached
      Descemet membrane. Case 6 was a repeat DALK; the OCT guided the manual dissection
      of the residual stroma underlying the failed graft. In case 7, the OCT showed an
      intrastromal retention of fluid that was not detectable by the operating
      microscope due to diffuse scarring following alkaline injury. The OCT helped to
      assess the location of the Descemet membrane and guided the manual dissection.
      CONCLUSIONS: Intraoperative high-definition AS-OCT obtained good-quality images
      of the cornea during DALK and proved useful in various cases of DALK to help the
      surgeon decide on a number of surgical steps.

PMID- 24332370
TI  - XRN4 and LARP1 are required for a heat-triggered mRNA decay pathway involved in
      plant acclimation and survival during thermal stress.
AB  - To survive adverse and ever-changing environmental conditions, an organism must
      be able to adapt. It has long been established that the cellular reaction to
      stress includes the upregulation of genes coding for specific stress-responsive
      factors. In the present study, we demonstrate that during the early steps of the
      heat stress response, 25% of the Arabidopsis seedling transcriptome is targeted
      for rapid degradation. Our findings demonstrate that this process is catalyzed
      from 5' to 3' by the cytoplasmic exoribonuclease XRN4, whose function is
      seemingly reprogrammed by the heat-sensing pathway. The bulk of mRNAs subject to
      heat-dependent degradation are likely to include both the ribosome-released and
      polysome associated polyadenylated pools. The cotranslational decay process is
      facilitated at least in part by LARP1, a heat-specific cofactor of XRN4 required
      for its targeting to polysomes. Commensurate with their respective involvement at
      the molecular level, LARP1 and XRN4 are necessary for the thermotolerance of
      plants to long exposure to moderately high temperature, with xrn4 null mutants
      being almost unable to survive. These findings provide mechanistic insights
      regarding a massive stress-induced posttranscriptional downregulation and outline
      a potentially crucial pathway for plant survival and acclimation to heat stress. 

PMID- 24332372
TI  - Rotational stability of a single-piece toric acrylic intraocular lens: a pilot
      study.
AB  - PURPOSE: To evaluate the visual performance and rotational stability of the
      Tecnis Toric 1-piece intraocular lens (IOL) during the first 3 postoperative
      months. DESIGN: Prospective, single-center study. METHODS: In this study,
      patients with age-related cataract and corneal astigmatism of 1.0 to 3.0 diopters
      measured with the IOLMaster 500 (Carl Zeiss Meditec AG) were included. Before
      surgery, rotating Scheimpflug scans (Pentacam HR; Oculus) were performed and the
      cornea was marked in the sitting position at the slit lamp. Patients received a
      single-piece toric hydrophobic acrylic IOL (Tecnis Toric; AMO). Immediately and 3
      months after surgery, retroillumination photographs were obtained to assess the
      rotational stability of the IOL. Additionally, Autorefraction (Topcon),
      subjective refraction, uncorrected and distance-corrected visual acuity,
      keratometry, and Scheimpflug and ocular wavefront (WASCA, Carl Zeiss Meditec AG)
      measurements were performed at the 3-month follow-up. RESULTS: Thirty eyes of 30
      patients were included in this study. Mean absolute difference between the IOL
      axis at the 3-month and 1-hour follow-up was 2.7 degrees (standard deviation, 3.0
      degrees). The IOL rotation was less than 3 degrees and less than 6 degrees in 62%
      and 95% of all cases, respectively. CONCLUSIONS: The Tecnis Toric 1-piece IOL is
      rotationally stable and shows excellent capsule bag performance and refractive
      outcomes.

PMID- 24332373
TI  - Conjunctival flora antibiotic resistance patterns after serial intravitreal
      injections without postinjection topical antibiotics.
AB  - PURPOSE: To report conjunctival bacterial flora antibiotic resistance patterns
      after serial intravitreal injections performed using a povidone-iodine
      preparation without the use of preinjection or postinjection topical antibiotics.
      DESIGN: Prospective, interventional case series. METHODS:  SETTING: Single-center
      clinical practice in Pennsylvania. STUDY POPULATION: Thirteen eyes of 13
      treatment-naive patients undergoing serial intravitreal anti-vascular endothelial
      growth factor (VEGF) injections for exudative age-related macular degeneration or
      macular edema attributable to retinal vein occlusion. INTERVENTION: Conjunctival
      cultures from the treatment eye were performed prior to each injection
      preparation. A minimum of 3 monthly conjunctival cultures were obtained per eye
      over the course of the study. Ocular surface preparation consisted of topical
      anesthetic and povidone-iodine 5% without the use of preinjection or
      postinjection topical antibiotics. MAIN OUTCOME MEASURES: Conjunctival flora
      growth patterns and antibiotic resistance patterns to several common antibiotics
      tested over the course of the study. RESULTS: A total of 48 cultures were
      performed with a 77% culture positivity rate. Over the course of the serial
      conjunctival cultures in each patient, there was no evidence for emergence of
      resistant bacteria to any of the tested antibiotics (including fluoroquinolones
      and azithromycin) or significant alteration from baseline conjunctival flora. Of
      the 47 bacterial isolates, the most commonly isolated organism was coagulase
      negative Staphylococcus both at baseline (73%) and following serial intravitreal
      injections (78%, P = .73). CONCLUSIONS: Ocular surface preparation for
      intravitreal injection using povidone-iodine 5% alone in the absence of
      postinjection topical antibiotics does not appear to promote bacterial resistance
      or a discernible change in conjunctival flora.

PMID- 24332375
TI  - Vitreoretinal complications and vitreoretinal surgery in osteo-odonto
      keratoprosthesis surgery.
AB  - PURPOSE: To describe the indications for and approaches to vitreoretinal surgery
      in patients with osteo-odonto-keratoprosthesis (OOKP). DESIGN: Retrospective case
      series. METHODS: This was a retrospective review of all patients who had
      undergone OOKP surgery between 2003 and 2012 at our center. OOKP procedures were
      performed for severe ocular surface disease according to the indications and
      techniques described in the patient demographics of the Rome-Vienna Protocol.
      Indications for retinal surgery, surgical outcomes, and intraoperative and
      postoperative complications were documented. Operative techniques were reviewed
      from the surgical records, and any subsequent surgeries were also recorded.
      RESULTS: Thirty-six patients underwent OOKP, and retinal surgery was indicated in
      13 (36%). The indications for and approaches to surgery were retinal detachment
      repair using an Eckardt temporary keratoprosthesis; assessment of retina and
      optic nerve health prior to OOKP surgery, using either a temporary
      keratoprosthesis or an endoscope; endoscopic cyclophotocoagulation for
      intractable glaucoma; endoscopic trimming of a retroprosthetic membrane; or
      vitrectomy for endophthalmitis with visualization through the OOKP optic using
      the binocular indirect viewing system. In all cases, retinal surgical aims were
      achieved with a single procedure. Postoperative vitreous hemorrhage occurred in
      16 patients (44%), but all resolved spontaneously. CONCLUSIONS: OOKPs represent
      the last hope for restoration of vision in severe ocular surface disease, and the
      retinal surgeon is frequently called upon in the assessment and management of
      these patients. Temporary keratoprostheses and endoscopic vitrectomies are
      valuable surgical tools in these challenging cases, improving functional outcomes
      without compromising OOKP success.

PMID- 24332374
TI  - Axial biometry of the entire eye using ultra-long scan depth optical coherence
      tomography.
AB  - PURPOSE: To assess the repeatability of axial biometry of the entire eye using
      ultra-long scan depth optical coherence tomography (OCT) and to investigate the
      agreement with IOLMaster measurements (Carl Zeiss Meditec). DESIGN: Prospective,
      observational case series. METHODS: There were 37 adult subjects enrolled in
      group 1 and 12 adult subjects enrolled in group 2. Using ultra-long scan depth
      OCT, the left eyes of these groups were measured in 2 separate sessions. The
      images were processed by a manual method and custom-developed automatic software.
      A model eye was imaged for verification. The subjects in group 2 were imaged
      using ultra-long scan depth OCT and using the IOLMaster for axial length
      measurement comparison. RESULTS: All measured parameters of the model eye matched
      the geometric parameters. In group 1, there were no significant differences in
      all measured parameters using automatic and manual segmentation methods (P > .05,
      paired t test). The percentage of coefficient of repeatability of segments ranged
      from 0.3% to 3.9%. The corresponding interclass correlation coefficients ranged
      from 0.946 to 0.999. The correlation between the results using automatic and
      manual segmentation methods appeared to be strong (R(2) = 0.999; P < .05). In
      group 2, the axial length of the eye measured by the IOLMaster matched the
      results obtained by ultra-long scan depth OCT with the automatic method (R1(2) =
      0.987; P < .05) and the manual method (R2(2) = 0.988; P < .05). CONCLUSIONS:
      Automatic axial biometry using ultra-long scan depth OCT successfully measured
      each segment of the entire eye with good repeatability. With further development
      of automatic segmentation, ultra-long scan depth OCT seems to be a promising tool
      in the axial biometry of the entire eye.

PMID- 24332376
TI  - Efficacy of short-term postoperative perfluoro-n-octane tamponade for pediatric
      complex retinal detachment.
AB  - PURPOSE: To evaluate the efficacy of perfluoro-n-octane as a postoperative short
      term tamponade after vitrectomy in pediatric cases with complex retinal
      detachment (RD) and proliferative vitreoretinopathy (PVR). DESIGN: Prospective,
      noncomparative, interventional case series. METHODS: The medical records of 10
      eyes of 9 children (6 boys and 3 girls), whose age ranged from 3 months to 11
      years, with a median of 7.5 months, were reviewed. The cause of the PVR was
      retinopathy of prematurity (7 eyes of 6 patients); familial exudative
      vitreoretinopathy; or tractional RD associated with congenital optic nerve
      anomalies,(1) and persistent fetal vasculature. Perfluoro-n-octane was injected
      into the eyes at the primary surgery in 2 eyes and at the repeat surgeries in 8
      eyes. The perfluoro-n-octane was removed after 1 to 4 postoperative weeks. The
      patients were followed for 5 to 43 months. RESULTS: At the last examination, the
      retinas were reattached in 8 eyes (80%). In the other two eyes, a retinal
      attachment was not obtained. Postoperatively, the best-corrected visual acuity
      improved from hand motion to 0.1 in 1 eye and could not be measured in the other
      9 patients because of their ages. No apparent adverse events related to the use
      of perfluoro-n-octane were noted. CONCLUSIONS: Although cautions should be
      exercised regarding potential mechanical retinal injuries by heavy liquids in the
      eye, short-term perfluoro-n-octane tamponade was effective in pediatric cases
      with severe PVR in which retinal reattachment is considered to be difficult with
      conventional gas or silicone oil tamponade.

PMID- 24332377
TI  - High prevalence of demodex brevis infestation in chalazia.
AB  - PURPOSE: To investigate the correlation between demodicosis and chalazia in
      patients with the latter. DESIGN: Prospective, observational, comparative study.
      METHODS: Forty-four adult and 47 pediatric patients with chalazia and 34 adult
      and 30 pediatric age- and sex-matched patients without chalazia treated at an
      institutional referral eye center were included. All 155 patients underwent lash
      sampling followed by microscopic identification and counting of Demodex mites.
      All 91 patients with chalazia underwent surgical removal, and among them, 74 were
      followed up for 18 +/- 4.3 months after surgery. Statistical correlation between
      ocular demodicosis and chalazia and its postoperative recurrence was performed.
      RESULTS: Demodicosis was significantly more prevalent in chalazia patients than
      in control patients as a group (69.2% vs 20.3%) and when separated into pediatric
      (70.2% vs 13.3%) and adult (68.2% vs 26.5%) subgroups (all P < .001). Demodicosis
      was associated strongly with chalazia (odds ratio, 4.39; 95% confidence interval,
      2.17 to 8.87; P < .001). D. brevis was significantly more prevalent (odds ratio,
      18.21; 95% confidence interval, 2.22 to 149.74; P = .01) than D. folliculorum
      (odds ratio, 2.82; 95% confidence interval, 1.16 to 6.84, P = .02) in patients
      with chalazia. Patients with demodicosis tended to demonstrate recurrence (33.3%
      vs 10.3%; P = .02), especially in those with D. brevis (35.1% vs 13.5%; P = .03).
      CONCLUSIONS: There is a high prevalence of demodicosis, especially cases of
      caused by D. brevis, in adult and pediatric patients with chalazia, suggesting
      that ocular demodicosis is a risk factor for chalazia.

PMID- 24332378
TI  - Influence of tumor necrosis factor alpha inhibitors on testicular function and
      semen in spondyloarthritis patients.
AB  - OBJECTIVE: To evaluate sperm parameters and sexual hormones in young males
      affected with spondyloarthritis (SpA) before and after 1 year of anti-tumor
      necrosis factor (TNF) alpha treatment. DESIGN: Prospective case-control study.
      SETTING: Rheumatology and human reproduction pathology units at a university
      hospital. PATIENTS: Ten SpA outpatients attending the rheumatology clinic; 20
      healthy control subjects attending the unit of human reproduction pathology
      within an infertility prevention program. INTERVENTIONS: At baseline and after a
      12-month treatment, disease activity was assessed and an andrologic evaluation
      made. MAIN OUTCOME MEASURE(S): Rheumatologists assessed anamnestic, clinical,
      functional, and biomarker data. Andrologists evaluated semen analysis,
      fluorescence in situ hybridization for chromosomes X, Y, 13, 18, and 21, FSH, LH,
      and T plasma levels, and testicular color Doppler ultrasound. RESULTS: At
      baseline, SpA patients showed reduced sperm motility, higher plasma LH and FSH,
      and lower T levels compared with control subjects; a significant correlation
      between disease activity and sperm quality was found. After treatment, a
      statistically significant decrease in sperm aneuploidies and normal hormone
      levels were observed. CONCLUSIONS: Although inflammation in SpA appears to be
      related to impaired testicular function, anti-TNF-alpha agents seem to be safe on
      testicular function and fertility.

PMID- 24332379
TI  - Predictors of anti-VEGF treatment response in neovascular age-related macular
      degeneration.
AB  - Currently available evidence on predictors of anti-vascular endothelial growth
      factor (VEGF) treatment response in neovascular age-related macular degeneration
      was reviewed. No meta-analysis of results is possible because of a lack of
      controlled and randomized trials, varying treatment regimes and outcome measures
      used, as well as suboptimal reporting. For genetic factors, most evidence to date
      has been generated for single nucleotide polymorphisms (SNPs) in the complement
      factor H (CFH), and VEGF-A genes. Just under half of the SNPs assessed in the CFH
      gene and 15% of the SNPs assessed in the VEGF gene were found to be associated
      with visual outcomes or the number of injections required during follow-up. Some
      evidence suggests association of worse treatment outcomes as well as a younger
      age at treatment onset with an increasing number of risk alleles in known risk
      genes (CFH and ARMS2/HTRA1) and polymorphisms in the VEGF-A gene. Clinical
      factors such as higher age, a better visual acuity (VA), a larger choroidal
      neovascularization (CNV) lesion at baseline, and a delay between symptom onset
      and initiation of treatment of more than 3 weeks also impact outcomes.
      Conversely, a worse acuity at baseline predicted more gain in vision. Overall,
      patients presenting with good acuity at baseline were more likely to have good VA
      at follow up, but the gain afforded by treatment was impacted by a ceiling
      effect. Most available evidence suggests a strong association of clinical factors
      such as age, baseline VA, and CNV lesion size with anti-VEGF treatment outcomes.
      No behavioral factors such as smoking influence treatment outcomes. Based on the
      studies conducted so far, the evidence suggests that underlying genotype of known
      AMD risk associated genes or of the VEGF-A gene have a limited effect, whereas
      presenting clinical factors appear to be more important in determining treatment
      outcomes.

PMID- 24332380
TI  - Incorporating screening, brief intervention, and referral to treatment into
      emergency nursing workflow using an existing computerized physician order
      entry/clinical decision support system.
AB  - INTRODUCTION: The objective of this study was to evaluate whether screening,
      brief intervention, and referral to treatment (SBIRT) could be incorporated into
      the emergency nursing workflow using a computerized physician order
      entry/clinical decision support system. We report demographic and operational
      factors associated with failure to initiate the protocol and revenue collection
      from SBIRT. METHODS: We conducted a retrospective, observational cohort analysis
      of a protocol adding SBIRT to the emergency nursing workflow of a single,
      tertiary care urban emergency department for all adult patient visits in 2012.
      Emergency nurses prescreened for unhealthy alcohol or drug use during triage
      assessment and, when positive, administered SBIRT during treatment area care, all
      documented in the computerized physician order entry/clinical decision support
      system. Using multivariable logistic regression, we report demographic and
      operational factors associated with failure to initiate the protocol. From
      October 2012, we submitted charges for brief interventions and analyzed
      collection results. RESULTS: The inclusion criteria were met for 47,693 visits.
      Of these, 39,758 (83.4%) received triage protocol initiation. Variables
      associated with decreased odds of protocol initiation were younger age (odds
      ratio [OR] for rising age, 1.044; 95% confidence interval [CI], 1.042-1.045),
      arrival by ambulance (OR, 0.37; 95% CI, 0.35-0.40), and higher triage acuity (OR,
      0.08; 95% CI, 0.07-0.09). Of visits with protocol initiation, 21.4% were
      documented as positive for at-risk alcohol and/or drug use. However, brief
      interventions were only administered during 971 visits. During the billing
      period, $3617.53 was collected on charges of $10,829.15 for 262 completed brief
      interventions. DISCUSSION: In this study electronic documentation of adults with
      at-risk alcohol and/or drug use was feasible by emergency nurses, but SBIRT
      execution and subsequent revenue collection were challenging.

PMID- 24332381
TI  - Postural stability and ankle sprain history in athletes compared to uninjured
      controls.
AB  - BACKGROUND: Diminished postural stability is a risk factor for ankle sprain
      occurrence and ankle sprains result in impaired postural stability. To date,
      ankle sprain history has not been taken into account as a determinant of postural
      stability, while it could possibly specify subgroups of interest. METHODS:
      Postural stability was compared between 18 field hockey athletes who had
      recovered from an ankle sprain (mean (SD); 3.6 (1.5) months post-injury), and 16
      uninjured controls. Force plate and kinematics parameters were calculated during
      single-leg standing: mean center of pressure speed, mean absolute horizontal
      ground reaction force, mean absolute ankle angular velocity, and mean absolute
      hip angular velocity. Additionally, cluster analysis was applied to the 'injured'
      participants, and the cluster with diminished postural stability was compared to
      the other participants with respect to ankle sprain history. FINDINGS: MANCOVA
      showed no significant difference between groups in postural stability (P = 0.68).
      A self-reported history of an (partial) ankle ligament rupture was typically
      present in the cluster with diminished postural stability. Subsequently, a
      'preceding rupture' was added as a factor in the MANCOVA, which showed a
      significant association between diminished postural stability and a 'preceding
      rupture' (P = 0.01), for all four individual parameters (P: 0.001-0.029; Cohen's
      d: 0.96-2.23). INTERPRETATION: Diminished postural stability is not apparent in
      all previously injured athletes. However, our analysis suggests that an (mild)
      ankle sprain with a preceding severe ankle sprain is associated with impaired
      balance ability. Therefore, sensorimotor training may be emphasized in this
      particular group and caution is warranted in return to play decisions.

PMID- 24332382
TI  - Clinical biomechanics of instability related to total knee arthroplasty.
AB  - BACKGROUND: Tibiofemoral instability is a common reason for total knee
      arthroplasty failure, and may be attributed to soft tissue deficiency and
      incorrect ligament balancing. There are many different designs of implant with
      varying levels of constraint to overcome this instability; however there is
      little advice for surgeons to assess which is suitable for a specific patient,
      and soft tissue balance testing during arthroplasty is very subjective. METHOD:
      The current theories on primary and secondary soft tissue restraints to
      anterior/posterior, varus/valgus, and internal/external rotational motion of the
      knee are discussed. The paper reviews biomechanics literature to evaluate
      instability in the intact and implanted knee. FINDINGS: The paper highlights
      important intra- and extra-capsular structures in the knee and describes the
      techniques used by clinicians to assess instability perioperatively. In vitro
      cadaveric studies were found to be a very useful tool in comparing different
      implants and contributions of different soft tissues. INTERPRETATION: In vitro
      cadaveric studies can be utilised in helping less experienced surgeons with soft
      tissue releases and determining the correct implant. For this to happen, more
      biomechanical studies must be done to show the impact of release sequences on
      implanted cadavers, as well as determining if increasingly constrained implants
      restore the stability of the knee to pre-deficient conditions.

PMID- 24332383
TI  - Preclinical FLT-PET and FDG-PET imaging of tumor response to the multi-targeted
      Aurora B kinase inhibitor, TAK-901.
AB  - INTRODUCTION: The Aurora kinases play a key role in mitosis and have recently
      been identified as attractive targets for therapeutic intervention in cancer. The
      aim of this study was therefore to investigate the utility of 3'-[(18)F]fluoro-3'
      deoxythymidine (FLT) and 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) for assessment
      of tumor response to the multi-targeted Aurora B kinase inhibitor, TAK-901.
      METHODS: Balb/c nude mice bearing HCT116 colorectal xenografts were treated with
      up to 30mg/kg TAK 901 or vehicle intravenously twice daily for two days on a
      weekly cycle. Tumor growth was monitored by calliper measurements and PET imaging
      was performed at baseline, day 4, 8, 11 and 15. Tumors were harvested at time
      points corresponding to days of PET imaging for analysis of ex vivo markers of
      cell proliferation and metabolism together with markers of Aurora B kinase
      inhibition including phospho-histone H3 (pHH3) and senescence associated beta
      galactosidase. RESULTS: Tumor growth was inhibited by 60% on day 12 of 30mg/kg
      TAK-901 therapy. FLT uptake was significantly reduced by day 4 of treatment and
      this corresponded with reduction in bromodeoxyuridine and pHH3 staining by
      immunohistochemistry. All biomarkers rebounded towards baseline levels by the
      commencement of the next treatment cycle, consistent with release of Aurora B
      kinase suppression. TAK-901 therapy had no impact on glucose metabolism as
      assessed by FDG uptake and GLUT1 staining by immunohistochemistry. CONCLUSIONS:
      FLT-PET, but not FDG-PET, is a robust non-invasive imaging biomarker of early
      HCT116 tumor response to the on-target effects of the multi-targeted Aurora B
      kinase inhibitor, TAK-901. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT
      CARE: This is the first report to demonstrate the impact of the multi-targeted
      Aurora B kinase inhibitor, TAK-901 on tumor FLT uptake. The findings provide a
      strong rationale for the evaluation of FLT-PET as an early biomarker of tumor
      response in the early phase clinical development of this compound.

PMID- 24332384
TI  - Improvement in quality of life with left prefrontal transcranial magnetic
      stimulation in patients with pharmacoresistant major depression: acute and six
      month outcomes.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) is a safe and effective
      treatment for major depression. We describe quality of life (QOL) outcomes from
      acute treatment with TMS, and describe the durability of benefit across 24-weeks.
      METHODS: Three hundred and one medication-free patients with pharmacoresistant
      major depression were randomized to active or sham TMS in a 6-week controlled
      trial. Nonresponders to the 6-week blinded phase of the study were enrolled in a
      6-week open-label study without unblinding the prior treatment assignment.
      Responders and partial responders to both the blinded (active or sham treatment)
      or open acute treatment phases were tapered off TMS over three weeks, while
      initiating maintenance antidepressant medication monotherapy. These subjects
      entered the 24-week study to examine the durability of response to TMS. The
      Medical Outcomes Study-36 Item Short Form (SF-36) and the Quality of Life
      Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were used to measure overall
      function and QOL. During the 24-week durability of effect study, QOL assessments
      were done at study entry and at the end of 24-weeks. RESULTS: Statistically
      significant improvement in both functional status and QOL outcomes was observed
      in patients treated with active TMS compared with sham TMS during the acute phase
      of the randomized, sham-controlled trial. Similar benefits were observed in
      patients who entered the open-label extension study. These improvements were
      sustained across the 24-week follow up study. CONCLUSIONS: Acute treatment with
      TMS improved functional status and QOL outcomes in patients with major
      depression. This clinical effect was durable in long-term follow up.

PMID- 24332385
TI  - Do theories of suicide play well together? Integrating components of the
      hopelessness and interpersonal psychological theories of suicide.
AB  - Given that suicide is a leading cause of death worldwide, there has been
      considerable research on theories of suicide risk. Despite the volume of such
      research, each theory is largely investigated in isolation and there has been
      little attempt to integrate them. Thus, the goal of the present study is to
      integrate two theories of suicide risk, Alloy and Abramson's hopelessness theory
      of suicide (HT) and Joiner's interpersonal psychological theory of suicide
      (IPTS), into one mediational model where the effects of the risk associated with
      the HT variables (i.e., a negative cognitive style) on suicidal ideation are
      transmitted by the IPTS (i.e., perceived burdensomeness and thwarted belonging)
      variables. Participants were 245 young adults with elevated levels of depressive
      symptoms who completed self-report measures of suicide risk at baseline and a
      measure of suicidal ideation eight weeks later. The results of a mediated model
      supported our hypothesis. The effects of the HT variables on suicidal ideation
      were mediated by the IPTS variables. Furthermore, results did not support the
      reverse model, suggesting specificity of the direction of our hypotheses. These
      findings imply that there may be merit in attempting to integrate theories of
      suicide risk rather than studying them in isolation. 

PMID- 24332386
TI  - Psychopathological features during childhood and adolescence among adult bipolar
      patients: a retrospective study.
AB  - OBJECTIVE: There are still several concerns regarding the inconsistency in the
      diagnosis of Bipolar Disorder (BD) in children and adolescents. This study
      reviews the symptoms of youth admitted to The University of Texas Harris County
      Psychiatric Center (UT-HCPC) prior to a confirmed diagnosis of BD to elucidate
      patterns and target symptoms which may facilitate early recognition of BD.
      METHODS: This is a retrospective review of charts of adult patients with a
      discharge diagnosis of BD for three consecutive admissions who were also admitted
      to UT-HCPC as children or adolescents (N=26). The Kiddie SADS was completed based
      on each patient's first admission as a child and last admission as an adult.
      RESULTS: Most of the symptoms found in adult BD were present in the
      child/adolescent subjects at equivalent rates, except for mood elevation, which
      was less common during childhood and adolescence. In spite of the
      psychopathological similarity, only 6 (23%) of the subjects were diagnosed with
      BD as youth. CONCLUSION: BD is poorly diagnosed among children and adolescents.
      Difficulties in the assessment of the youth, as well as particularities in the
      psychopathology of mood among children and adolescents may account for the low
      diagnostic rate.

PMID- 24332387
TI  - Association between subjective well-being and depressive symptoms in treatment
      resistant schizophrenia before and after treatment with clozapine.
AB  - BACKGROUND: We examined the relationship between subjective well-being and
      depressive symptoms in patients with treatment-resistant schizophrenia before and
      after treatment with clozapine to contribute to the growing body of research
      regarding the determinants of patients' perspective of their own well-being in
      schizophrenia. METHODS: Forty patients with treatment-resistant schizophrenia
      were comprehensively evaluated for subjective well-being, schizophrenic symptoms,
      and depressive symptoms before and 8 weeks after the initiation of treatment with
      clozapine. Correlation analysis and Fisher's z-transformation statistics were
      performed. RESULTS: There were significant improvements in all Positive and
      Negative Syndrome Scale (PANSS) factor scores and Beck Depression Inventory (BDI)
      score over the treatment period (P<.05). Before clozapine administration, the
      subjective well-being score had significant negative correlations with the PANSS
      depression factor score (P<.05) and the BDI score (P<.05). After clozapine
      treatment, the subjective well-being score still had significant negative
      correlations with the PANSS depression factor score (P<.05) and the BDI score
      (P<.05) and no new associations emerged with treatment. Fisher's z-transformation
      statistics revealed that the correlations between the subjective well-being score
      and the depression score were not significantly different before and after
      clozapine treatment. CONCLUSIONS: These results indicate that depressive symptoms
      are significantly associated with low subjective well-being in patients with
      treatment-resistant schizophrenia. The association was equally significant before
      and after treatment with clozapine, suggesting that the relationship does not
      change with clozapine treatment, even when depressive symptoms improve
      significantly, and that there may be a common pathophysiological basis for
      depressive symptoms and the subjective appraisal of well-being in schizophrenia.

PMID- 24332388
TI  - Self-image and suicide in a Swedish national eating disorders clinical register.
AB  - OBJECTIVE: Using a prospective design, to examine the relation between self-image
      (assessed using the Structural Analysis of Social Behavior) and suicide
      attempts/completions in women with anorexia nervosa-restricting type (ANR),
      anorexia nervosa-binge/purge type (ANBP), bulimia nervosa (BN), binge eating
      disorder (BED), and eating disorder not otherwise specified (EDNOS); and to
      assess whether these self-image variables add unique predictive value to suicide
      when considering other baseline predictors. METHOD: Women (N=2269) aged 12 to 45
      (M=22.1) presenting to specialist eating disorders clinics in Sweden between 2005
      and 2009 were identified through the Stepwise Eating Disorders Quality Register.
      Data on age, body mass index, eating disorder severity (Eating Disorder
      Examination-Questionnaire scores), psychiatric comorbidity, global assessment of
      functioning, and self-image were abstracted from Stepwise and included as
      baseline predictors or covariates. Suicide information (prior attempt and
      attempt/completion after Stepwise registration) was obtained from the National
      Patient Register and Cause of Death Register. RESULTS: Prevalence of detected
      suicide attempts/completions over the study period was 9.2%. Negative self-image
      variables were associated with prior suicide attempts in ANR and EDNOS and later
      suicide attempts/completions in women with BN. In a stepwise Cox proportional
      hazards model, only low self-affirmation predicted time to suicide
      attempts/completions in women with BN when accounting for age and prior suicide
      attempt. CONCLUSION: Assessing self-image might assist with identifying women
      with BN at elevated risk for suicide.

PMID- 24332389
TI  - Diagnostic point-of-care tests in resource-limited settings.
AB  - The aim of diagnostic point-of-care testing is to minimise the time to obtain a
      test result, thereby allowing clinicians and patients to make a quick clinical
      decision. Because point-of-care tests are used in resource-limited settings, the
      benefits need to outweigh the costs. To optimise point-of-care testing in
      resource-limited settings, diagnostic tests need rigorous assessments focused on
      relevant clinical outcomes and operational costs, which differ from assessments
      of conventional diagnostic tests. We reviewed published studies on point-of-care
      testing in resource-limited settings, and found no clearly defined metric for the
      clinical usefulness of point-of-care testing. Therefore, we propose a framework
      for the assessment of point-of-care tests, and suggest and define the term test
      efficacy to describe the ability of a diagnostic test to support a clinical
      decision within its operational context. We also propose revised criteria for an
      ideal diagnostic point-of-care test in resource-limited settings. Through
      systematic assessments, comparisons between centralised testing and novel point
      of-care technologies can be more formalised, and health officials can better
      establish which point-of-care technologies represent valuable additions to their
      clinical programmes. 

PMID- 24332390
TI  - Molecular mechanisms underlying the enhanced functions of three-dimensional
      hepatocyte aggregates.
AB  - Three-dimensional (3D) culture of hepatocytes leads to improved and prolonged
      synthetic and metabolic functions, but the underlying molecular mechanisms are
      unknown. In order to investigate the role of 3D cell-cell interactions in
      maintaining hepatocyte differentiated functions ex vivo, primary mouse
      hepatocytes were cultured either as monolayers on tissue culture dishes (TCD) or
      as 3D aggregates in rotating wall vessel (RWV) bioreactors. Global gene
      expression analyses revealed that genes upregulated in 3D culture were distinct
      from those upregulated during liver development and liver regeneration. Instead,
      they represented a diverse array of hepatocyte-specific functional genes with
      significant over-representation of hepatocyte nuclear factor 4alpha (Hnf4a)
      binding sites in their promoters. Expression of Hnf4a and many of its downstream
      target genes were significantly increased in RWV cultures as compared to TCD.
      Conversely, there was concomitant suppression of mesenchymal and cytoskeletal
      genes in RWV cultures that were induced in TCDs. These findings illustrate the
      importance of 3D cell-cell interactions in maintaining fundamental molecular
      pathways of hepatocyte function and serve as a basis for rational design of
      biomaterials that aim to optimize hepatocyte functions ex vivo for biomedical
      applications.

PMID- 24332392
TI  - Short-term mediating factors of a school-based intervention to prevent youth
      substance use in Europe.
AB  - PURPOSE: To investigate factors mediating the effects of a European school-based
      intervention (Unplugged) based on a social influence approach to youths'
      substance use. METHODS: Schools in seven European countries (n = 143, including
      7,079 pupils) were randomly assigned to an experimental condition (Unplugged
      curriculum) or a control condition (usual health education). Data were collected
      before (pretest) and 3 months after the end of the program (posttest). Multilevel
      multiple mediation models were applied to the study of effect mediation
      separately for tobacco, alcohol, and cannabis use. Analyses were conducted on the
      whole sample, and separately on baseline users and nonusers of each substance.
      RESULTS: Compared with the control group, participants in the program endorsed
      less positive attitudes toward drugs; positive beliefs about cigarettes, alcohol,
      and cannabis; and the normative perception of peers using tobacco and cannabis.
      They also increased in knowledge about all substances and refusal skills toward
      tobacco. Decreased positive attitudes toward drugs, increase in refusal skills,
      and reappraisal of norms about peer using tobacco and cannabis appeared to
      mediate the effects of the program on the use of substances. However, mediating
      effects were generally weak and some of them were only marginally significant.
      CONCLUSIONS: This study lends some support to the notion that school-based
      programs based on a social influence model may prevent juvenile substance use
      through the modification of attitudes, refusal skills, and normative perceptions.

PMID- 24332391
TI  - Differential effects of cell adhesion, modulus and VEGFR-2 inhibition on
      capillary network formation in synthetic hydrogel arrays.
AB  - Efficient biomaterial screening platforms can test a wide range of extracellular
      environments that modulate vascular growth. Here, we used synthetic hydrogel
      arrays to probe the combined effects of Cys-Arg-Gly-Asp-Ser (CRGDS) cell adhesion
      peptide concentration, shear modulus and vascular endothelial growth factor
      receptor 2 (VEGFR2) inhibition on human umbilical vein endothelial cell (HUVEC)
      viability, proliferation and tubulogenesis. HUVECs were encapsulated in
      degradable poly(ethylene glycol) (PEG) hydrogels with defined CRGDS concentration
      and shear modulus. VEGFR2 activity was modulated using the VEGFR2 inhibitor
      SU5416. We demonstrate that synergy exists between VEGFR2 activity and CRGDS
      ligand presentation in the context of maintaining HUVEC viability. However,
      excessive CRGDS disrupts this synergy. HUVEC proliferation significantly
      decreased with VEGFR2 inhibition and increased modulus, but did not vary
      monotonically with CRGDS concentration. Capillary-like structure (CLS) formation
      was highly modulated by CRGDS concentration and modulus, but was largely
      unaffected by VEGFR2 inhibition. We conclude that the characteristics of the ECM
      surrounding encapsulated HUVECs significantly influence cell viability,
      proliferation and CLS formation. Additionally, the ECM modulates the effects of
      VEGFR2 signaling, ranging from changing the effectiveness of synergistic
      interactions between integrins and VEGFR2 to determining whether VEGFR2
      upregulates, downregulates or has no effect on proliferation and CLS formation.

PMID- 24332393
TI  - Socioeconomic and clinical characteristics associated with repeat suicide
      attempts among young people.
AB  - PURPOSE: Repeat suicidal behaviors in young people are a critical public health
      concern. The study investigates individual socioeconomic and episode-dependent
      clinical factors predicting repeat suicide attempts among youth by gender.
      METHODS: Using a retrospective cohort study, we identified a total of 4,094 male
      and 3,219 female youths who had the index suicide episode at the ages of 15-24
      years from the 1996-2007 National Health Insurance Research Database in Taiwan.
      The recurrence of suicide attempt was assessed within 1 year after the index
      suicide. Information pertaining to suicide management and postsuicide treatment
      was obtained from healthcare records. Repeated event survival analyses were used
      to estimate episode-dependent risk of suicide attempt. RESULTS: The occurrence of
      repeat suicide attempts was more common in males, yet the phenomenon of risk
      aggravation appears more prominent in females. The estimate for peak hazard of
      the second repeat attempt was 2-fold higher than that of the first repeat event
      in males, and approximately 6-fold in females. Socioeconomic (e.g., labor market
      participation: adjusted Hazard Ratio [aHR] = 1.14, 95% CI = 1.01-1.28) and index
      suicide management characteristics (e.g., receiving treatment at clinic, aHR =
      1.54, 95% CI = 1.19-1.99) were found to play important roles for repeat suicide
      attempts in males. For females, postsuicide treatment of mental disorders appears
      more influential. CONCLUSIONS: The relationships between socioeconomic and
      clinical factors with repeat suicide attempts in young people vary by gender.
      School/workplace-based post suicide attempt consultation and clinical management
      for youth may be planned and delivered on a gender-appropriate basis.

PMID- 24332394
TI  - Healthcare providers' beliefs and attitudes about electronic cigarettes and
      preventive counseling for adolescent patients.
AB  - PURPOSE: Electronic cigarettes (e-cigarettes) are battery-powered nicotine
      delivery systems that may serve as a "gateway" to tobacco use by adolescents. Use
      of e-cigarettes by U.S. adolescents rose from 3% in 2011 to 7% in 2012. We sought
      to describe healthcare providers' awareness of e-cigarettes and to assess their
      comfort with and attitudes toward discussing e-cigarettes with adolescent
      patients and their parents. METHODS: A statewide sample (n = 561) of Minnesota
      healthcare providers (46% family medicine physicians, 20% pediatricians, and 34%
      nurse practitioners) who treat adolescents completed an online survey in April
      2013. RESULTS: Nearly all providers (92%) were aware of e-cigarettes, and 11%
      reported having treated an adolescent patient who had used them. The most
      frequently cited sources of information about e-cigarettes were patients, news
      stories, and advertisements, rather than professional sources. Providers
      expressed considerable concern that e-cigarettes could be a gateway to tobacco
      use but had moderately low levels of knowledge about and comfort discussing e
      cigarettes with adolescent patients and their parents. Compared with
      pediatricians and nurse practitioners, family medicine physicians reported
      knowing more about e-cigarettes and being more comfortable discussing them with
      patients (both p < .05). Nearly all respondents (92%) wanted to learn more about
      e-cigarettes. CONCLUSIONS: Healthcare providers who treat adolescents may need to
      incorporate screening and counseling about e-cigarettes into routine preventive
      services, particularly if the prevalence of use continues to increase in this
      population. Education about e-cigarettes could help providers deliver
      comprehensive preventive services to adolescents at risk of tobacco use.

PMID- 24332395
TI  - A novel tumor: specimen index for assessing adequacy of resection in early stage
      oral tongue cancer.
AB  - PURPOSE: Surgical margin status frequently affects decisions regarding adjuvant
      treatment; however, reporting and interpretation of surgical margins is subject
      to considerable subjectivity because of many factors including the adequacy of
      resection. We developed a novel measure of the adequacy of surgical resection,
      the tumor: specimen index (TSI), and tested its utility at predicting clinical
      outcomes in a retrospective cohort study. PATIENTS AND METHODS: An institutional
      database was queried to identify previously untreated patients with T1 and T2
      oral tongue cancer who underwent surgery during 1985-2009 (n=433). The TSI, a
      geometric mean representing the percentage of the surgical specimen that is
      occupied by the tumor in average single dimension, was calculated from the
      largest measured lengths, widths, and heights of the tumor in relation to the
      entire surgical specimen. Multivariate analyses of locoregional recurrence-free
      probability (LRRFP) and disease-specific survival (DSS) were performed with
      commonly accepted prognosticators in addition to TSI and surgical margins status.
      RESULTS: The mean TSI was 41 (range 11-90; SD 14). Surgical margin status was
      associated with TSI; margins were negative in 84% of patients with TSI<45 and in
      63% of patients with TSI?45 (p<0.001). TSI?45 was associated with worse LRRFP
      (57% vs. 76%, p<0.001) and worse DSS (68% vs. 85%, p<0.001). In a multivariate
      analysis that did not include TSI, surgical margin status independently predicted
      LRRFP (p=0.014) but not DSS. When TSI was included, only TSI, and not surgical
      margin status, was an independent predictor of both LRRFP (p=0.002) and DSS
      (p=0.011). CONCLUSION: The tumor: specimen index is an easily-calculated metric
      for estimating the adequacy of 3-dimensional resection in T1 and T2 oral tongue
      cancer that independently predicts oncologic outcomes.

PMID- 24332396
TI  - Incorporating uncertainty regarding applicability of evidence from meta-analyses
      into clinical decision making.
AB  - OBJECTIVES: Judging applicability (relevance) of meta-analytical findings to
      particular clinical decision-making situations remains challenging. We aimed to
      describe an evidence synthesis method that accounts for possible uncertainty
      regarding applicability of the evidence. STUDY DESIGN AND SETTING: We
      conceptualized uncertainty regarding applicability of the meta-analytical
      estimates to a decision-making situation as the result of uncertainty regarding
      applicability of the findings of the trials that were included in the meta
      analysis. This trial-level applicability uncertainty can be directly assessed by
      the decision maker and allows for the definition of trial inclusion
      probabilities, which can be used to perform a probabilistic meta-analysis with
      unequal probability resampling of trials (adaptive meta-analysis). A case study
      with several fictitious decision-making scenarios was performed to demonstrate
      the method in practice. RESULTS: We present options to elicit trial inclusion
      probabilities and perform the calculations. The result of an adaptive meta
      analysis is a frequency distribution of the estimated parameters from traditional
      meta-analysis that provides individually tailored information according to the
      specific needs and uncertainty of the decision maker. CONCLUSION: The proposed
      method offers a direct and formalized combination of research evidence with
      individual clinical expertise and may aid clinicians in specific decision-making
      situations.

PMID- 24332398
TI  - The role of parents and partners in minors' decisions to have an abortion and
      anticipated coping after abortion.
AB  - PURPOSE: Despite the prevalence of laws requiring parental involvement in minors'
      abortion, little is known about the effect of parental involvement on minors'
      abortion decision making and anticipated coping after abortion. METHODS: We
      analyzed data from medical charts and counseling needs assessment forms for 5,109
      women accessing abortion services at a clinic in 2008, 9% (n = 476) of whom were
      minors aged 17 years and under. We examined differences in abortion
      characteristics, including parental and partner involvement, between minors and
      adults, and used multivariate logistic regression models to examine predictors of
      parental involvement and support, confidence in the decision, and anticipated
      poor coping among minors. RESULTS: Most minors reported that their mothers (64%)
      and partners (83%) were aware of their abortion. Younger age was associated with
      increased odds of maternal awareness and reduced odds of partner awareness.
      Compared with adults, minors were more likely to report external pressure to seek
      abortion (10% vs. 3%), and mothers were the most common source of pressure.
      Minors overall had high confidence in their decision and anticipated feeling a
      range of emotions post-abortion; minors who felt pressure to seek abortion were
      less likely to report having confidence in their decision (odds ratio = .1) and
      more likely to report anticipating poor coping (odds ratio = 5.6). CONCLUSIONS:
      Most minors involve parents and partners in their decision making regarding
      abortion, and find support from these individuals. For a minority, experiencing
      pressure or lack of support reduces confidence in their decision and increases
      their likelihood of anticipating poor coping after an abortion.

PMID- 24332397
TI  - A new method to address verification bias in studies of clinical screening tests:
      cervical cancer screening assays as an example.
AB  - OBJECTIVES: Studies to evaluate clinical screening tests often face the problem
      that the "gold standard" diagnostic approach is costly and/or invasive. It is
      therefore common to verify only a subset of negative screening tests using the
      gold standard method. However, undersampling the screen negatives can lead to
      substantial overestimation of the sensitivity and underestimation of the
      specificity of the diagnostic test. Our objective was to develop a simple and
      accurate statistical method to address this "verification bias." STUDY DESIGN AND
      SETTING: We developed a weighted generalized estimating equation approach to
      estimate, in a single model, the accuracy (eg, sensitivity/specificity) of
      multiple assays and simultaneously compare results between assays while
      addressing verification bias. This approach can be implemented using standard
      statistical software. Simulations were conducted to assess the proposed method.
      An example is provided using a cervical cancer screening trial that compared the
      accuracy of human papillomavirus and Pap tests, with histologic data as the gold
      standard. RESULTS: The proposed approach performed well in estimating and
      comparing the accuracy of multiple assays in the presence of verification bias.
      CONCLUSION: The proposed approach is an easy to apply and accurate method for
      addressing verification bias in studies of multiple screening methods.

PMID- 24332399
TI  - Evaluation of gold and silver leaching from printed circuit board of cellphones.
AB  - Electronic waste has been increasing proportionally with the technology. So,
      nowadays, it is necessary to consider the useful life, recycling, and final
      disposal of these equipment. Metals, such as Au, Ag, Cu, Sn and Ni can be found
      in the printed circuit boards (PCB). According to this, the aims of this work is
      to characterize the PCBs of mobile phones with aqua regia; obtaining "reference"
      values of leaching, to gold and silver, with cyanide and nitric acid,
      respectively; and study the process of leaching of these metals in alternative
      leaching with sodium thiosulfate and ammonium thiosulfate. The metals were
      characterized by digesting the sample with aqua regia for 1 and 2h at 60 degrees
      C and 80 degrees C. The leaching of Au with a commercial reagent (cyanide) and
      the Ag with HNO3were made. The leaching of Au and Ag with alternative reagents:
      Na2S2O3, and (NH4)2S2O3 in 0.1M concentration with the addition of CuSO4, NH4OH,
      and H2O2, was also studied. The results show that the digestion with aqua regia
      was efficient to characterize the metals present in the PCBs of mobile phones.
      However, the best method to solubilize silver was by digesting the sample with
      nitric acid. The leaching process using sodium thiosulfate was more efficient
      when an additional concentration of 0.015 and 0.030 M of the CuSO4 was added.

PMID- 24332400
TI  - Time-series product and substance flow analyses of end-of-life electrical and
      electronic equipment in China.
AB  - Given the amounts of end-of-life electrical and electronic equipment (EoL-EEE)
      being generated and their contents of both harmful and valuable materials, the
      EoL-EEE issue should be regarded not only as an emerging environmental problem
      but also as a resource management strategy in China. At present, in order to
      provide the basis for managing EoL-EEE at both product and substance levels in
      China, it is necessary to carry out a quantitative analysis on EoL-EEE and to
      determine how much of it will be generated and how much materials and substances
      it contains. In this study, the possession and obsolescence amounts of five types
      of household appliance (HA) including television (TV) sets and the amounts of
      substances contained in EoL TV sets were estimated using time-series product flow
      analysis (PFA) and substance flow analysis (SFA). The results of PFA indicated
      that the total possession amounts of those five types of HAs will exceed 3.1
      billion units in 2030, which will be two times higher than those in 2010. In
      addition, it was estimated that cumulatively over 4.8-5.1 billion units of these
      five types of EoL HA would be obsoleted between 2010-2030. The results of SFA on
      TV sets indicated that the generated amounts of most of the less common metals
      and a part of common metals such as copper (Cu) would tend to decrease, whereas
      those of other common metals such as iron (Fe) as well as precious metals would
      tend to increase in EoL TV sets in 2015-2030. The results of this study provide a
      quantitative basis for helping decision makers develop strategic policies for the
      management of EoL-EEE considering both environmental and resource aspects.
      Moreover, a calculation scheme of obsolete HAs presented in this study can be
      applied to estimate other types of EoL durable good. Meanwhile, the frameworks of
      this study will help not only the policy decision makers in the Chinese
      government but also those in developing countries that are facing similar
      problems. 

PMID- 24332402
TI  - Retrieval of a large foreign body from the ileum with double-balloon enteroscopy
      (with videos).

PMID- 24332401
TI  - Genotyping Toxoplasma gondii from wildlife in Pennsylvania and identification of
      natural recombinants virulent to mice.
AB  - Recent studies indicated the predominance of Toxoplasma gondii haplogroup 12 in
      wildlife in the USA. However, still little is known of the genetic diversity of
      this parasite circulating in wildlife. In the present study, we tested coyotes
      (Canis latrans), red foxes (Vulpes vulpes), white-tailed deer (Odocoileus
      virginianus), and geese (Branta canadensis) from the state of Pennsylvania for T.
      gondii infection. Antibodies to T. gondii were found in 160 of 367 animals,
      including 92 (34.5%) of 266 coyotes, 49 (62.0%) of 79 white-tailed deer, 17
      (85.0%) of 20 red fox, and two of two Canada geese tested by the modified
      agglutination test (cut off titer 1:25). Tissues from 105 seropositive animals
      were bioassayed in mice, and viable T. gondii was isolated from 29 animals,
      including 10 of 53 coyotes, 11 of 16 foxes, 7 of 49 deer, and one of one goose.
      DNA isolated from culture-derived tachyzoites of these isolates was characterized
      initially using multilocus PCR-RFLP markers. Nine genotypes were revealed,
      including ToxoDB PCR-RFLP #1 (4 isolates), #2 (2 isolates), #3 (4 isolates), #4
      (6 isolates), #5 (4 isolates), #54 (1 isolate), #141 (1 isolate), #143 (1
      isolate), and #216 (6 isolates), indicating high genetic diversity of T. gondii
      in wildlife in Pennsylvania. Pathogenicity of six T. gondii isolates (5 of #216
      and #141) was determined in outbred Swiss Webster mice. Three of #216 and the
      #141 isolates were acute virulent to mice, and the other 2 #216 isolates were
      intermediate virulent. To determine the extent of genetic variation of these as
      well as a few recently reported virulent isolates from wildlife in North America,
      intron sequences were generated. Analysis of intron sequences and PCR-RFLP
      genotyping results indicated that the #216 isolates are likely derived from
      recombination of the clonal type I and III lineages. To determine if T. gondii
      virulence can be predicted by typing, we genotyped a collection of strains using
      PCR-RFLP markers for polymorphic genes ROP5, ROP16, ROP18 and GRA15, which are
      known to interact with host immune response. The results showed that there is an
      association of genotypes of ROP5 and ROP18 with mouse-virulence, however,
      additional gene(s) may also contribute to virulence in distinct T. gondii
      genotypes. 

PMID- 24332403
TI  - Over-the-scope clip closure of pancreaticocolonic fistula caused by severe
      necrotizing pancreatitis.

PMID- 24332404
TI  - Preoperative visualization of mucin-producing gallbladder carcinoma by using
      peroral transcatheter cholecystoscopy technique (with video).

PMID- 24332405
TI  - The role of endoscopy in the evaluation and management of dysphagia.

PMID- 24332406
TI  - Duration of untreated psychosis predicts functional and clinical outcome in
      children and adolescents with first-episode psychosis: a 2-year longitudinal
      study.
AB  - Longer duration of untreated psychosis (DUP) in adult patients with first-episode
      psychosis (FEP) has been associated with poor clinical and social outcomes. We
      aimed to estimate the influence of DUP on outcome at 2-year follow-up in subjects
      with an early-onset (less than 18 years of age) FEP of less than 6 months'
      duration. A total of 80 subjects (31.3% females, mean age 16.0+/-1.8 years) were
      enrolled in the study. The influence of DUP on outcome was estimated using
      multiple regression models (two linear models for influence of DUP on the C-GAF
      at 2 years and C-GAF change through the follow-up period, and a logistic model
      for influence of DUP on 41 PANSS remission at 2 years in schizophrenia patients
      (n=47)). Mean DUP was 65.3+/-54.7 days. Median DUP was 49.5 days. For the whole
      sample (n=80), DUP was the only variable significantly related to C-GAF score at
      2-year follow-up (Beta=-0.13, p<0.01), while DUP and premorbid adjustment (Beta=
      0.01, p<0.01; and Beta=-0.09, p=0.04, respectively) were the only variables
      significantly related to C-GAF change. In schizophrenia patients, DUP predicted
      both C-GAF score at 2 years and C-GAF change, while in patients with affective
      psychosis (n=22), DUP was unrelated to outcome. Lower baseline C-GAF score
      (OR=0.91, p<0.01) and shorter DUP (OR=0.98, p=<0.01) were the only variables that
      significantly predicted clinical remission in schizophrenia patients. In
      conclusion, longer DUP was associated with lower C-GAF at 2 years, less increase
      in C-GAF, and lower rates of clinical remission in early-onset FEP. Our findings
      support the importance of early detection programs, which help shorten DUP.

PMID- 24332407
TI  - The varieties of anomalous self experiences in schizophrenia: splitting of the
      mind at a crossroad.

PMID- 24332408
TI  - Contributors to childhood obesity in Iran: the views of parents and school staff.
AB  - OBJECTIVE: To explore the contextual influences on childhood obesity in Tehran,
      Iran to inform future development of an obesity prevention intervention for
      Iranian primary school children. STUDY DESIGN: Qualitative study. METHODS: Focus
      groups and interviews with parents and school staff were convened to explore
      their perceptions of the causes of childhood obesity. Eleven focus groups and
      three interviews were held with parents and school staff (88 participants in
      total) from three different socio-economic areas in Iran's capital city, Tehran.
      All the discussions were transcribed verbatim in Persian. An iterative thematic
      approach was used for data analysis. RESULTS: Overall, the causes of childhood
      obesity were perceived to relate to macro-level policy influences, the school
      environment, sociocultural factors, and family and individual behavioural
      factors, acting in combination. A key emergent theme was the pervasive influence
      of Government policies on children's food intake and physical activity. Another
      key theme was the political and sociocultural context that does not support girls
      and women in Iran in having active lifestyles. CONCLUSION: The findings suggest
      that parents and school staff have sophisticated views on the possible causes of
      childhood overweight and obesity which encompassed behavioural, structural and
      social causes. A prominent emerging theme was the need for state level
      intervention and support for a healthy environment. Any local initiatives in Iran
      are unlikely to be successful without such support. WHAT IS KNOWN ON THIS
      SUBJECT: Childhood obesity is growing in Iran and it is seen as one of the
      features of the nutrition transition in developing countries. Findings from cross
      sectional studies suggest a range of lifestyle factors contribute to obesity in
      the Iranian population. WHAT THIS STUDY ADDS: This qualitative study explores the
      socioenvironmental changes contributing to childhood obesity in primary school
      aged children in Iran. Findings have provided important contextual data on the
      perceived contributors to childhood obesity in Iran, such as macro-level policy
      influences on accessibility to healthy food and physical activity, competing
      priorities at school level, sociocultural influences on diet and physical
      activity and limited knowledge and skills of parents. This has laid the
      foundation for the development of appropriate childhood obesity prevention
      interventions.

PMID- 24332409
TI  - Pulmonary rehabilitation improves long-term outcomes in interstitial lung
      disease: a prospective cohort study.
AB  - BACKGROUND: Pulmonary rehabilitation improves outcomes in patients with
      interstitial lung disease (ILD), however it is unclear whether these effects are
      long lasting and which patients benefit most. METHODS: Patients with ILD were
      recruited into this prospective cohort study from three pulmonary rehabilitation
      programs. Patients completed functional assessments (6-minute walk distance
      (6MWD), and 4-meter walk time) and surveys (quality of life, dyspnea, depression,
      and physical activity) before rehabilitation, after rehabilitation, and at six
      months. Changes from baseline were compared using a paired t-test. Independent
      predictors of change in 6MWD and quality of life were determined using
      multivariate analysis. RESULTS: Fifty-four patients were recruited (22 with
      idiopathic pulmonary fibrosis), 50 patients (93%) completed the rehabilitation
      program, and 39 returned for six-month follow-up. 6MWD improved 57.6 m
      immediately after rehabilitation (95% confidence interval (CI) 40.2-75.1 m, p <
      0.0005), and remained 49.8 m above baseline at six months (95%CI 15.0-84.6 m, p =
      0.005). The majority of patients achieved the minimum clinically important
      difference for quality of life (51%), dyspnea (65%), and depression score (52%)
      immediately after rehabilitation, and improvements were still significant at 6
      month follow-up for quality of life, depression, and physical activity. A low
      baseline 6MWD was the only independent predictor of improvement in 6MWD during
      rehabilitation (r = -0.49, p < 0.0005). Change in 6MWD was an independent
      predictor of change in quality of life (r = -0.36, p = 0.01). CONCLUSIONS:
      Pulmonary rehabilitation improved multiple short- and long-term outcomes in
      patients with ILD. While all patients appear to benefit, ILD patients with a low
      baseline 6MWD had greater benefit from rehabilitation. CLINICAL TRIALS
      REGISTRATION NUMBER: NCT01055730 (clinicaltrials.gov).

PMID- 24332410
TI  - Porous chitosan bilayer membrane containing TGF-beta1 loaded microspheres for
      pulp capping and reparative dentin formation in a dog model.
AB  - OBJECTIVES: The objectives of this study were to develop a chitosan bilayer
      membrane containing microspheres with sustained TGF-beta1 release to enhance
      odontoblast-like cell function in vitro, and to investigate pulp-capping in a dog
      model to promote reparative dentin formation in vivo for the first time. METHODS:
      A chitosan bilayer membrane was synthesized consisting of a dense film on one
      side and a macroporous sponge on the other side. The rationale was to use the
      dense film to block the perforated pulp from bacterial invasion, and the porous
      sponge to be loaded with microspheres containing TGF-beta1 (MS-TGF) for sustained
      release. Pulp capping in 48 teeth of six beagle dogs was performed to test four
      groups: Control with no pulp capping material, commercial Dycal, chitosan
      membrane without MS-TGF, and chitosan membrane with MS-TGF. The dog teeth were
      harvested for histological analysis at two time points (10 and 60 d). RESULTS:
      The spongy side of the membrane had macropores with a mean size of 151 MUm. The
      porosity of the membrane was 83%. Chitosan microspheres containing TGF-beta1
      showed sustained release, gradually releasing 42% of the TGF-beta1 in 7 d. The
      proliferation of odontoblast-like cells on membrane with MS-TGF was much greater
      than that without TGF (p<0.05). At 10d, H&E staining revealed mild to moderate
      pulp inflammation in all four groups, with no dentin bridge formation. At 60 d,
      pulp inflammation disappeared, but there was no reparative dentin bridge in the
      group with no pulp-capping material. Chitosan membranes with MS-TGF generated
      reparative dentin with a thickness of (142+/-29) MUm, 3-6 times thicker than that
      with Dycal or chitosan bilayer membrane without TGF (p<0.05). SIGNIFICANCE: A
      novel chitosan bilayer-microsphere construct containing TGF-beta1 for pulp
      capping generated 3-6 times more reparative dentin than the controls in a dog
      model for the first time. The chitosan bilayer-microsphere construct with growth
      factor delivery may be useful for a wide range of dental and regenerative
      medicine applications.

PMID- 24332411
TI  - Evidence of hepatitis A virus circulation in central Argentina: seroprevalence
      and environmental surveillance.
AB  - BACKGROUND: Hepatitis A virus (HAV) has shown intermediate endemicity in
      Argentina, but notification of clinical cases has decreased since the
      introduction of the vaccine in 2005. OBJECTIVES: In order to get insight into the
      local circulation of this virus after four years of the official introduction of
      the vaccine, the aims of this study were to provide information on HAV immune
      status of the adult population of Cordoba city and to conduct environmental
      surveillance of HAV in sewage and river samples in the same region. STUDY DESIGN:
      The prevalence of anti-HAV was determined by EIA in 416 samples of people
      (without prior vaccination) from Cordoba city (2009-2010). Spline regression
      models were estimated under generalized additive models. Environmental
      surveillance was conducted in river and sewage samples collected in the same
      period. Viral detection was performed by RT-Nested PCR of the 5'UTR. RESULTS: In
      Cordoba, the global prevalence of anti-HAV was 73.5%. It increased with age
      (p<0.0001) and it was associated with the low-income population (OR: 1.14; 95% CI
      1.05-1.25). This prevalence decreased in younger age groups, especially in the
      high-income population. Environmental monitoring revealed the presence of HAV
      (IA) in 20.8% and 16.1% of wastewater and river samples, respectively.
      CONCLUSIONS: As a consequence of a decrease in HAV circulation due to
      improvements in immunization, socio-economic and hygienic conditions, young
      adults are becoming increasingly susceptible to HAV infections. Environmental
      monitoring demonstrated that HAV circulates in the local population; therefore,
      health care systems should consider the implementation of preventive measures for
      susceptible adults in order to reduce the risk of HAV infection.

PMID- 24332413
TI  - Pulmonary embolism following total knee arthroplasty in Taiwanese patients.
AB  - BACKGROUND: Pulmonary embolism is a relatively uncommon, but serious,
      postoperative complication of hip and knee arthroplasty; however, little
      information is available about the prevalence of pulmonary embolism in Taiwan.
      METHODS: We report here a series of five patients who sustained a symptomatic
      pulmonary embolism after undergoing total knee arthroplasty (TKA). These patients
      were identified during a retrospective study of 1768 patients carried out between
      January 2007 and January 2010. RESULTS: Five (0.28%) patients who sustained a
      symptomatic pulmonary embolism after TKA were identified in a series of 1768
      patients. The diagnosis was confirmed by computed tomography angiography findings
      in four patients and an increased d-dimer level in one patient. All the patients
      were women, with a mean age of 68.0 years (range 64-76 years). The average body
      mass index of these patients was 32.6 kg/m(2) (24-38 kg/m(2)). Four patients
      underwent simultaneous bilateral TKA, and one patient who was undergoing
      unilateral TKA also underwent revision TKA for a previously treated contralateral
      knee. None of the patients had a history of pulmonary embolism, and none was
      given prophylaxis for venous thromboembolism. The time at which pulmonary
      embolism occurred ranged from 2 to 8 days in five patients. After treatment, no
      patient had died by the end of the follow-up period. These case reports highlight
      the equal incidence of pulmonary embolism after TKA in Taiwanese and Western
      populations. CONCLUSION: Steps to prevent pulmonary embolism should be undertaken
      in selected patients, such as these patients with a high body mass index and
      simultaneous bilateral TKA.

PMID- 24332412
TI  - Comparison of the effect of reduced-fluence photodynamic therapy with
      intravitreal bevacizumab and standard-fluence alone for polypoidal choroidal
      vasculopathy.
AB  - BACKGROUND: Photodynamic therapy (PDT) has previously been reported to be
      effective in treating polypoidal choroidal vasculopathy (PCV), with satisfactory
      polyp regression. However, the optimum treatment protocol remains controversial.
      This study compared the effect of reduced-fluence PDT combined with intravitreal
      bevacizumab (rPDT/IVB) and standard-fluence PDT (sPDT) alone for treating
      symptomatic PCV in Chinese patients. METHODS: A retrospective review was carried
      out of the medical records of patients with PCV who were treated with rPDT/IVB
      (14 eyes of 13 patients) or sPDT (12 eyes of 12 patients) with at least 6 months
      of follow-up. RESULTS: The mean best-corrected visual acuity of the rPDT/IVB
      group improved significantly at the 6-month follow-up (p = 0.041). Only one eye
      (7.1%) in the rPDT/IVB group showed a decrease in visual acuity, compared with
      four eyes (33.3%) in the sPDT group. A total of 40.0% of eyes in the sPDT group
      showed increased lipid exudate at follow-up 1 month after treatment, whereas no
      increase in lipid exudate was observed in the rPDT/IVB group (p = 0.015). The
      mean maximum area of post-treatment hemorrhage in the rPDT/IVB group was smaller
      than that in the sPDT group (2.57 +/- 2.74 mm(2) vs. 12.69 +/- 10.28 mm(2), p =
      0.042). CONCLUSION: Combination therapy with rPDT/IVB for patients with PCV
      showed encouraging results in vision improvement, a lower decrease in visual
      acuity, significantly less post-treatment lipid exudate and a smaller area of
      post-treatment hemorrhage at the 6-month follow-up than patients treated with
      sPDT.

PMID- 24332414
TI  - Determinants of low-density lipoprotein cholesterol goal attainment: Insights
      from the CEPHEUS Pan-Asian Survey.
AB  - BACKGROUND: Previous studies have reported that the attainment of goals for low
      density lipoprotein cholesterol (LDL-C) are globally suboptimal, but contemporary
      data are scarce. The CEntralized Pan-Asian survey on tHE Under-treatment of
      hypercholeSterolemia (CEPHEUS-PA) is the largest evaluation of pharmacological
      treatment for hypercholesterolemia in Asia. The study reported here analyzed the
      Taiwan cohort in CEPHEUS-PA to identify the determinants of successful treatment.
      METHODS: The patients eligible for this study were adults (>=18 years old) with
      hypercholesterolemia and with at least two coronary heart disease (CHD) risk
      factors who had been receiving lipid-lowering drugs for at least 3 months before
      enrollment, without adjustment for at least 6 weeks before enrollment.
      Demographic and clinical information and lipid concentrations were recorded.
      Cardiovascular risk levels and LDL-C targets were determined using the updated
      Adult Treatment Panel III. RESULTS: In this group of 999 Taiwanese patients, 50%,
      25%, and 24% had LDL-C goals set at <70 mg/dL, <100 mg/dL, and <130 mg/dL,
      respectively. The overall attainment rate was 50%, with the lowest rate in
      patients set at the most stringent target (22%), followed by those whose
      therapeutic goals were <100 mg/dL (69%) and <130 mg/dL (87%). The success of LDL
      C control was lower in patients with multiple risk factors other than CHD or its
      equivalents than in those without these multiple risk factors (37% vs. 53%, p <
      0.001), and lower in patients with metabolic syndrome than in those without (43%
      vs. 66%, p < 0.001). Baseline LDL-C and cardiovascular risk were inversely
      associated with goal attainment, whereas treatment with statins was directly
      associated with the achievement of LDL-C goals. Patients with diabetes (odds
      ratio 0.49, 95% confidence interval 0.29-0.84, p = 0.010) and with metabolic
      syndrome (odds ratio 0.15, 95% confidence interval 0.05-0.40, p < 0.001) were
      less likely to be treated with statins. CONCLUSION: This study showed that there
      is a discrepancy between the updated Adult Treatment Panel III recommendations
      for LDL-C control and the control attained by this group of Taiwanese patients.
      In particular, treatment with statins was largely underused in patients with
      diabetes and in those with metabolic syndrome. These findings highlight the need
      for more intensive treatment in high-risk patients and those with multiple risk
      factors, particularly patients with metabolic syndrome.

PMID- 24332415
TI  - Atrial fibrillation influences survival in patients with hepatocellular
      carcinoma: experience from a single center in Taiwan.
AB  - BACKGROUND: It is unclear whether atrial fibrillation (AF) adversely influences
      the clinical course of patients with hepatocellular carcinoma (HCC). METHODS:
      During the period from January 1, 2001 to December 31, 2010, 476 patients (mean
      +/- SD age 60.3 +/- 12.9 years) diagnosed with HCC were retrospectively enrolled
      in our study. The HCC stage, treatment, baseline characteristics, underlying
      cardiovascular diseases, and corresponding drug treatment were systematically
      reviewed. The primary endpoint was death from any cause. RESULTS: AF was
      associated with a significantly reduced survival time in patients with HCC (AF
      vs. non-AF patients mean +/- SD survival time 470.1 +/- 89.6 days vs. 1161.2 +/-
      32.6 days, log-rank p < 0.001; probability of survival 0.20, 95% confidence
      interval 0.10-0.38, p < 0.001). After adjustment for sex and age, AF was still
      associated with poorer survival times (hazard ratio 4.131, 95% confidence
      interval 2.134-5.733, p < 0.001). The causes of death among 22 patients with both
      HCC and AF included 11 cases of hepatic failure, four cases of ruptured tumor,
      and two cases of bleeding from esophageal varices. None of these patients with AF
      used warfarin. Seven bleeding events related to HCC were noted, but none of these
      patients developed a major thromboembolism. The mean +/- SD follow-up period was
      645 +/- 468 days. CONCLUSION: Patients with HCC had a significantly reduced
      survival time with the comorbidity of AF. Tumor rupture was relatively common
      among patients with both HCC and AF. The anticoagulation treatment of AF in
      patients with HCC deviated from the current guidelines without an increase in
      thromboembolic events.

PMID- 24332416
TI  - Impact of coronary anatomy and stenting technique on long-term outcome after drug
      eluting stent implantation for unprotected left main coronary artery disease.
AB  - OBJECTIVES: This study sought to evaluate the impact of anatomic and procedural
      variables on the outcome of the unprotected left main coronary artery (uLMCA)
      itself after drug-eluting stent (DES) implantation. BACKGROUND: There is a
      controversial debate regarding when and how to perform percutaneous coronary
      intervention (PCI) for an uLMCA stenosis. METHODS: This analysis is based on a
      randomized study of 607 patients undergoing PCI for uLMCA, randomized 1:1 to
      receive paclitaxel- or sirolimus-eluting stents. We evaluated the impact of the
      SYNTAX score, uLMCA anatomy, and stenting technique on in-stent restenosis (ISR),
      target lesion revascularization (TLR), and the 3-year outcomes. RESULTS: The 3
      year cardiac mortality rate was 5.8%; 235 (39%) patients had a true bifurcation
      lesion (TBL), and the median SYNTAX score was 27. TBL was associated with a
      higher need for multiple stents (72% vs. 37%, p < 0.001). TBL was a significant
      predictor of ISR (23% vs. 14%, p = 0.008) and for TLR (18% vs. 9%, p < 0.001).
      The need for multiple stents was a predictor of ISR (22% vs. 13%, p = 0.005) and
      for TLR (16% vs. 9%, p = 0.005). Culotte stenting showed better results compared
      with T-stenting for ISR (21% vs. 56%, p = 0.02) and for TLR (15% vs. 56%, p <
      0.001). We observed a significant association between uLMCA-TLR and SYNTAX scores
      (9.2% for scores <= 22, 14.9% for scores 23 to 32, and 13.0% for scores >= 33, p
      = 0.008). CONCLUSIONS: PCI of uLMCA lesions with DES is safe and effective out to
      3 years. TBL and multiple stents were independent predictors for ISR. In the
      multivariate analysis, independent predictors for TLR were TBL, age, and
      EuroSCORE (European System for Cardiac Operative Risk Evaluation). (Drug-Eluting
      Stents for Unprotected Left Main Stem Disease [ISAR-LEFT-MAIN]; NCT00133237).

PMID- 24332417
TI  - Evolving concepts in the management of left main coronary disease.

PMID- 24332418
TI  - A novel noninvasive technology for treatment planning using virtual coronary
      stenting and computed tomography-derived computed fractional flow reserve.
AB  - OBJECTIVES: This study sought to determine whether computational modeling can be
      used to predict the functional outcome of coronary stenting by virtual stenting
      of ischemia-causing stenoses identified on the pre-treatment model. BACKGROUND:
      Computed tomography (CT)-derived fractional flow reserve (FFR) is a novel
      noninvasive technology that can provide computed (FFRct) using standard coronary
      CT angiography protocols. METHODS: We prospectively enrolled 44 patients (48
      lesions) who had coronary CT angiography before angiography and stenting, and
      invasively measured FFR before and after stenting. FFRct was computed in blinded
      fashion using coronary CT angiography and computational fluid dynamics before and
      after virtual coronary stenting. Virtual stenting was performed by modification
      of the computational model to restore the area of the target lesion according to
      the proximal and distal reference areas. RESULTS: Before intervention, invasive
      FFR was 0.70 +/- 0.14 and noninvasive FFRct was 0.70 +/- 0.15. FFR after stenting
      and FFRct after virtual stenting were 0.90 +/- 0.05 and 0.88 +/- 0.05,
      respectively (R = 0.55, p < 0.001). The mean difference between FFRct and FFR was
      0.006 for pre-intervention (95% limit of agreement: -0.27 to 0.28) and 0.024 for
      post-intervention (95% limit of agreement: -0.08 to 0.13). Diagnostic accuracy of
      FFRct to predict ischemia (FFR <= 0.8) prior to stenting was 77% (sensitivity:
      85.3%, specificity: 57.1%, positive predictive value: 83%, and negative
      predictive value: 62%) and after stenting was 96% (sensitivity: 100%,
      specificity: 96% positive predictive value: 50%, and negative predictive value:
      100%). CONCLUSIONS: Virtual coronary stenting of CT-derived computational models
      is feasible, and this novel noninvasive technology may be useful in predicting
      functional outcome after coronary stenting. (Virtual Coronary Intervention and
      Noninvasive Fractional Flow Reserve [FFR]; NCT01478100).

PMID- 24332419
TI  - Comparison of newer-generation drug-eluting with bare-metal stents in patients
      with acute ST-segment elevation myocardial infarction: a pooled analysis of the
      EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial
      INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible
      Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction)
      trials.
AB  - OBJECTIVES: This study sought to study the efficacy and safety of newer
      generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an
      appropriately powered population of patients with ST-segment elevation myocardial
      infarction (STEMI). BACKGROUND: Among patients with STEMI, early generation DES
      improved efficacy but not safety compared with BMS. Newer-generation DES,
      everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to
      improve clinical outcomes compared with early generation DES. METHODS: Individual
      patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized
      clinical trials comparing newer-generation DES with BMS were pooled: 1,326
      patients received a newer-generation DES (everolimus-eluting stent or biolimus A9
      eluting stent), whereas the remaining 1,329 patients received a BMS. Random
      effects models were used to assess differences between the 2 groups for the
      device-oriented composite endpoint of cardiac death, target-vessel reinfarction,
      and target-lesion revascularization and the patient-oriented composite endpoint
      of all-cause death, any infarction, and any revascularization at 1 year. RESULTS:
      Newer-generation DES substantially reduce the risk of the device-oriented
      composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95%
      confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the
      patient-oriented composite endpoint was lower with newer-generation DES than BMS
      (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer
      generation DES were driven by both a lower risk of repeat revascularization of
      the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk
      of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer
      generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95%
      CI: 0.16 to 0.75; p = 0.006) compared with BMS. CONCLUSIONS: Among patients with
      STEMI, newer-generation DES improve safety and efficacy compared with BMS
      throughout 1 year. It remains to be determined whether the differences in favor
      of newer-generation DES are sustained during long-term follow-up.

PMID- 24332421
TI  - Defining the flow-limiting stenosis noninvasively for management of patients with
      coronary artery disease.

PMID- 24332420
TI  - Two-year outcomes after first- or second-generation drug-eluting or bare-metal
      stent implantation in all-comer patients undergoing percutaneous coronary
      intervention: a pre-specified analysis from the PRODIGY study (PROlonging Dual
      Antiplatelet Treatment After Grading stent-induced Intimal hyperplasia studY).
AB  - OBJECTIVES: This study sought to assess device-specific outcomes after
      implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint
      stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents
      (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients
      undergoing percutaneous coronary intervention. BACKGROUND: Few studies have
      directly compared second-generation drug-eluting stents with each other or with
      BMS. METHODS: We randomized 2,013 patients to BMS, ZES-S, PES, or EES
      implantation. At 30 days, each stent group received up to 6 or 24 months of
      clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse
      cardiac event (MACE) including any death, myocardial infarction, or target vessel
      revascularization, whereas the cumulative rate of definite or probable stent
      thrombosis (ST) was the key safety endpoint. RESULTS: Clinical follow-up at 2
      years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%;
      95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1
      to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%;
      95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year
      incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in
      the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with
      the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi
      square = 16.9; p = 0.0001). CONCLUSIONS: Our study shows that cumulative MACE
      rate, encompassing both safety and efficacy endpoints, was lowest for EES,
      highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS
      also with respect to the safety endpoints with regard to definite or probable and
      definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after
      Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

PMID- 24332422
TI  - Periprocedural myocardial injury in chronic total occlusion percutaneous
      interventions: a systematic cardiac biomarker evaluation study.
AB  - OBJECTIVES: This study sought to evaluate the incidence, correlates, and clinical
      implications of periprocedural myocardial injury (PMI) during percutaneous
      coronary intervention (PCI) of chronic total occlusions (CTO). BACKGROUND: The
      risk of PMI during CTO PCI may be underestimated because systematic cardiac
      biomarker measurement was not performed in published studies. METHODS: We
      retrospectively examined PMI among 325 consecutive CTO PCI performed at our
      institution between 2005 and 2012. Creatine kinase-myocardial band fraction and
      troponin were measured before PCI and 8 to 12 h and 18 to 24 h after PCI in all
      patients. PMI was defined as creatine kinase-myocardial band increase >= 3 x the
      upper limit of normal. Major adverse cardiac events during mid-term follow-up
      were evaluated. RESULTS: Mean age was 64 +/- 8 years. The retrograde approach was
      used in 26.8% of all procedures. The technical and procedural success was 77.8%
      and 76.6%, respectively. PMI occurred in 28 patients (8.6%, 95% confidence
      intervals: 5.8% to 12.2%), with symptomatic ischemia in 7 of those patients. The
      incidence of PMI was higher in patients treated with the retrograde than the
      antegrade approach (13.8% vs. 6.7%, p = 0.04). During a median follow-up of 2.3
      years, compared with patients without PMI, those with PMI had a higher incidence
      of major adverse cardiac events (hazard ratio [HR]: 2.25, p = 0.006). Patients
      with only asymptomatic PMI also had a higher incidence of major adverse cardiac
      events on follow-up (HR: 2.26, p = 0.013). CONCLUSIONS: Systematic measurement of
      cardiac biomarkers post-CTO PCI demonstrates that PMI occurs in 8.6% of patients,
      is more common with the retrograde approach, and is associated with worse
      subsequent clinical outcomes during mid-term follow-up.

PMID- 24332423
TI  - The EXAMINATION trial (Everolimus-Eluting Stents Versus Bare-Metal Stents in ST
      Segment Elevation Myocardial Infarction): 2-year results from a multicenter
      randomized controlled trial.
AB  - OBJECTIVES: This study sought to assess the 2-year outcomes of the population
      included in the EXAMINATION (Everolimus-Eluting Stents Versus Bare-Metal Stents
      in ST-Segment Elevation Myocardial Infarction) trial beyond the 1-year
      prescription period of dual antiplatelet therapy. BACKGROUND: The EXAMINATION
      trial compared the performance of everolimus-eluting stents (EES) versus bare
      metal stents (BMS) in an all-comer ST-segment elevation myocardial infarction
      (STEMI) population. METHODS: This was a multicenter, multinational, prospective,
      randomized, single-blind, controlled trial in patients with STEMI. The primary
      endpoint, which was the combined endpoint of all-cause death, any recurrent
      myocardial infarction, and any revascularization, and the endpoints target lesion
      revascularization and stent thrombosis were assessed at 2 years. RESULTS: Between
      December 31, 2008, and May 15, 2010, 1,498 patients were randomized to receive
      EES (n = 751) or BMS (n = 747). Compliance with dual antiplatelet regimen was
      reduced at 2 years to a similar degree (17.3% vs. 17.2%, p = 0.91). At 2 years,
      the primary endpoint occurred in 108 (14.4%) patients of the EES group and in 129
      (17.3%) patients of the BMS group (p = 0.11). Rate of target lesion
      revascularization was significantly lower in the EES group than in the BMS group
      (2.9% vs. 5.6%; p = 0.009). Rates of definite and definite or probable stent
      thrombosis were also significantly reduced in the EES group (0.8% vs. 2.1%; p =
      0.03, and 1.3% vs. 2.8%; p = 0.04, respectively). CONCLUSIONS: The 2-year follow
      up of the EXAMINATION trial confirms the safety and efficacy of the EES compared
      with BMS in the setting of STEMI. Specifically, both rates of target lesion
      revascularization and stent thrombosis were reduced in recipients of EES without
      any signs of late attrition for either of these endpoints. (A Clinical Evaluation
      of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST
      Segment Elevation Myocardial Infarction: EXAMINATION Study; NCT00828087).

PMID- 24332424
TI  - The absorb bioresorbable vascular scaffold in coronary bifurcations: insights
      from bench testing.
AB  - OBJECTIVES: This study sought to evaluate the feasibility of performing
      contemporary bifurcation techniques with the Absorb everolimus-eluting
      bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California) (BVS).
      BACKGROUND: The feasibility of using the BVS in bifurcation lesions is unknown.
      METHODS: We performed bifurcation stenting procedures including main-vessel
      stenting with ballooning of the side branch through the BVS struts, T-stenting
      and crush and culotte procedures, in a synthetic arterial model. Low-pressure
      final kissing balloon (FKB) inflation was performed to complete the procedures.
      RESULTS: Single-stent procedures optimally opened the side-branch ostium without
      deforming the main vessel BVS. T-stenting completely covered the side-branch
      ostium. In crush cases, we could easily re-cross the crushed BVS with the wire
      and balloon and achieve good results after deployment of the main-vessel BVS and
      FKB inflation. A 2-BVS culotte resulted in good paving of the main vessel.
      Disruption of 1 BVS strut was observed after FKB inflation with the 2 balloons
      inflated beyond the recommended limit of the BVS, as calculated by Finet's law.
      CONCLUSIONS: Intervention of bifurcation lesions using the Absorb BVS using
      modern bifurcation techniques appears feasible in a coronary bifurcation model.
      Provisional stenting is recommended in the majority, with sequential balloon
      inflations and FKB inflation only when necessary. T or T-stenting and small
      protrusion stenting with a metal drug-eluting stent is preferable in case of
      crossover. A2-BVS, T-stent technique can be performed in a high-angle
      bifurcation; otherwise, crush or culotte should be considered, using metal DES in
      the side branch. Two-BVS crush and culotte require careful evaluation, and should
      only be considered in patients with large-caliber main vessels.

PMID- 24332426
TI  - We have much in common: the similar inter-generational work preferences and
      career satisfaction among practicing radiologists.
AB  - PURPOSE: There are many reported generational differences regarding workplace
      motivators, but these have not been previously studied in radiologists. The aim
      of this study was to assess for generational differences in workplace
      satisfaction and desired workplace characteristics among practicing radiologists.
      METHODS: An electronic survey distributed to ACR, Society of Chairs of Academic
      Radiology Departments, and Association of Program Directors in Radiology members
      generated 1,577 responses from baby boom (BG) and generation X (GX) radiologists
      in active practice. Nineteen workplace characteristics and their associations
      with workplace satisfaction were tested in a univariate analysis using chi(2)
      tests and in a multiple logistic regression model to test for associations with
      satisfaction. RESULTS: Workplace satisfaction among BG and GX radiologists was
      78% and 80%, respectively. Both generations reported higher satisfaction if they
      were optimistic about the future of radiology (87% of BG vs 85% of GX
      radiologists), believed the difference in the desired versus expected age of
      retirement was narrow (1.5 +/- 3.3 years for BG radiologists vs 3.0 +/- 4.1 years
      for GX radiologists), felt that social interactions in the workplace were
      important (81% of BG vs 83% of GX radiologists), and believed that
      professionalism in their peers was important (79% of BG vs 82% of GX
      radiologists). BG radiologists were more satisfied if they valued staff
      diversity, while GX radiologists were more satisfied if they felt that job
      security and the amount of compensation were important. There was no significant
      association of satisfaction with generation, gender, practice setting, or
      additional administrative work. CONCLUSIONS: Workplace satisfaction among
      practicing radiologists remains high but has decreased compared with prior
      surveys. The two dominant generations of practicing radiologists have similar
      workplace satisfaction rates and desired workplace characteristics.

PMID- 24332427
TI  - The potential impact of accountable care organizations with respect to cost and
      quality with special attention to imaging.
AB  - An accountable care organization is a form of a managed care organization in
      which a group of networked health care providers, which may include hospitals,
      group practices, networks of practices, hospital-provider partnerships, or joint
      ventures, are accountable for the health care of a defined group of patients.
      Initial results of the institutions participating in CMS's Physician Group
      Demonstration Project did not demonstrate a substantial reduction in imaging that
      could be directly attributed to the accountable care organization model. However,
      the initial results suggest that incentive-based methodology appears to be
      successful for increasing compliance for measuring quality metrics. 

PMID- 24332428
TI  - Acute impacts of extreme temperature exposure on emergency room admissions
      related to mental and behavior disorders in Toronto, Canada.
AB  - BACKGROUND: The purpose of this study was to assess the effects of extreme
      ambient temperature on hospital emergency room visits (ER) related to mental and
      behavioral illnesses in Toronto, Canada. METHODS: A time series study was
      conducted using health and climatic data from 2002 to 2010 in Toronto, Canada.
      Relative risks (RRs) for increases in emergency room (ER) visits were estimated
      for specific mental and behavioral diseases (MBD) after exposure to hot and cold
      temperatures while using the 50th percentile of the daily mean temperature as
      reference. Poisson regression models using a distributed lag non-linear model
      (DLNM) were used. We adjusted for the effects of seasonality, humidity, day-of
      the-week and outdoor air pollutants. RESULTS: We found a strong association
      between MBD ER visits and mean daily temperature at 28 degrees C. The association
      was strongest within a period of 0-4 days for exposure to hot temperatures. A 29%
      (RR=1.29, 95% CI 1.09-1.53) increase in MBD ER vists was observed over a
      cumulative period of 7 days after exposure to high ambient temperature (99th
      percentile vs. 50th percentile). Similar associations were reported for
      schizophrenia, mood, and neurotic disorers. No significant associations with cold
      temperatures were reported. LIMITATIONS: The ecological nature and the fact that
      only one city was investigated. CONCLUSIONS: Our findings suggest that extreme
      temperature poses a risk to the health and wellbeing for individuals with mental
      and behavior illnesses. Patient management and education may need to be improved
      as extreme temperatures may become more prevalent with climate change.

PMID- 24332429
TI  - G0S2--a new player in leukemia.

PMID- 24332430
TI  - "And Isn't that the point?": pleasure and contraceptive decisions.
AB  - OBJECTIVE: Previous survey research indicates that women and men experience
      reduced sexual pleasure when using condoms, especially compared to nonbarrier
      family planning methods. This study seeks to explore those experiences of reduced
      pleasure in-depth and how they affect contraceptive method decisions and use.
      STUDY DESIGN: In-depth interviews with 30 men and 30 women between the ages of 18
      and 36 years in the United States about their contraceptive decisions and use
      were analyzed. RESULTS: Both men and women complained about the way that condoms
      interfered with their sexual pleasure. Several women (and no men) complained that
      condoms actually hurt them, and the majority of couples had at least one member
      who reported disliking condoms. For hormonal methods and intrauterine devices,
      general side effects were usually one of the most important reasons that women
      continued or discontinued methods, but few sexual side effects were reported.
      CONCLUSIONS: Interfering with sexual pleasure appears to be the most important
      reason that both men and women do not use condoms, and public health
      practitioners should recognize the limitations of condoms as a contraceptive
      technology. Despite problems with general side effects, most women (and men)
      prefer hormonal methods to condoms. IMPLICATIONS: This study provides in-depth
      descriptions showing that young adult men and women in the United States use
      condoms less because condoms interfere with their sexual pleasure. Although women
      often say they experience general negative side effects from hormonal birth
      control, they usually perceive few sexual side effects from hormonal birth
      control. Since young heterosexual adults usually perceive themselves to be at
      much greater risk for pregnancy than sexually transmitted infections, they mostly
      perceive hormonal birth control to be a greatly superior contraceptive option
      compared to condoms.

PMID- 24332431
TI  - A two-pill sublingual misoprostol outpatient regimen following mifepristone for
      medical abortion through 70 days' LMP: a prospective comparative open-label
      trial.
AB  - OBJECTIVE: To test the effectiveness and acceptability of an outpatient medical
      abortion protocol with 200 mg mifepristone and 400 mcg sublingual misoprostol at
      64-70 days' last menstrual period (LMP) and compare it to the already known
      efficacy of the 57-63 days' LMP gestational age range. STUDY DESIGN: We conducted
      a prospective, comparative open-label trial in six hospitals and clinics in
      Ukraine, Georgia, India and Tunisia. We enrolled 714 reproductive age women with
      pregnancies 57 to 70 days who presented requesting abortion. Medical abortions
      were managed with the current service delivery protocol (200 mg oral mifepristone
      followed in 24-48 h by 400 mcg sublingual misoprostol). Data on safety, efficacy
      and acceptability were collected. The main outcome measure was complete abortion
      without surgical intervention at any point. RESULTS: A total of 703 cases were
      analyzable for efficacy. Success rates did not differ significantly in the two
      groups [57-63-day group: 94.8%; 64-70-day group: 91.9%; Relative Risk (RR): 0.79
      (0.61-1.04)]. Ongoing pregnancy rates also did not differ significantly (57-63
      days: 1.8%; 64-70 days: 2.2%; RR: 1.10 (0.65-1.87)]. CONCLUSION: A medical
      abortion regimen of 200 mg mifepristone followed in 24-48 h by 400 mcg sublingual
      misoprostol is effective through 70 days' gestation and may be offered within
      existing outpatient abortion services. IMPLICATIONS: A regimen of 200 mg
      mifepristone followed in 24-48 h by 400 mcg sublingual misoprostol is effective
      up to 70 days' LMP. The findings have important implications for expanding access
      to outpatient medical abortion services in settings where the cost of misoprostol
      is of concern or a two-pill misoprostol regimen is the standard of care.

PMID- 24332432
TI  - Preference for Sayana(r) Press versus intramuscular Depo-Provera among HIV
      positive women in Rakai, Uganda: a randomized crossover trial.
AB  - INTRODUCTION: Sayana Press (SP), a subcutaneous formulation of depot
      medroxyprogesterone acetate (DMPA) prefilled in a Uniject injection system, could
      potentially improve and expand contraceptive injection services, but
      acceptability of SP is unknown. HIV-positive women need contraception to avoid
      unintended pregnancy and risk of vertical HIV transmission. We assessed
      acceptability of SP versus intramuscular DMPA (DMPA-IM) among HIV-positive women
      and their care providers in Rakai, Uganda. METHODS: Women were randomized to DMPA
      IM or SP at baseline, received the alternate product at 3 months, and chose their
      preferred method at 6 months. We determined preferences among new and experienced
      contraceptive injectable users who had tried both types of injection during the
      trial, and from providers before and after providing both types of injectables to
      clients. RESULTS: Among 357 women randomized, 314 were followed up at 6 months
      (88%). Although SP caused more skin irritation than DMPA-IM (3.8% vs. 0% at 6
      months, p=.03), it was associated with marginally fewer side effects (30.4% vs.
      40.4% at 6 months, p=.06). Participants reported high levels of willingness to
      recommend the DMPA contraception to a friend and satisfaction with the injection
      received, and these did not differ by injection type. Sixty-four percent of women
      and 73% of providers preferred SP to DMPA-IM at 6 months; women's preferences did
      not differ by previous experience with injectable contraception. CONCLUSIONS: SP
      is acceptable to HIV-positive women and health care providers in this rural
      Ugandan population. IMPLICATIONS: SP appears to be acceptable to HIV-positive
      women and their care providers in Rakai, Uganda, and strategies for appropriate
      rollout of this innovative technology should be explored.

PMID- 24332433
TI  - Emergency contraception with a copper IUD or oral levonorgestrel: an
      observational study of 1-year pregnancy rates.
AB  - OBJECTIVE: We investigated the 1-year pregnancy rates for emergency contraception
      (EC) users who selected the copper T380 intrauterine device (IUD) or oral
      levonorgestrel (LNG) for EC. STUDY DESIGN: This prospective study followed women
      for 1 year after choosing either the copper T380 IUD or oral LNG for EC. The
      study was powered to detect a 6% difference in pregnancy rates within the year
      after presenting for EC. RESULTS: Of the 542 women who presented for EC, agreed
      to participate in the trial and met the inclusion criteria, 215 (40%) chose the
      copper IUD and 327 (60%) chose oral LNG. In the IUD group, 127 (59%) were
      nulligravid. IUD insertion failed in 42 women (19%). The 1-year follow-up rate
      was 443/542 (82%); 64% of IUD users contacted at 1 year still had their IUDs in
      place. The 1-year cumulative pregnancy rate in women choosing the IUD was 6.5%
      vs. 12.2% in those choosing oral LNG [hazard ratio (HR) 0.53, 95% confidence
      interval (CI): 0.29-0.97, p=.041]. By type of EC method actually received,
      corresponding values were 5.2% for copper IUD users vs. 12.3% for oral LNG users
      (HR 0.42, 95% CI: 0.20-0.85, p=.017). A multivariable logistic regression model
      controlling for demographic variables demonstrates that women who chose the IUD
      for EC had fewer pregnancies in the following year than those who chose oral LNG
      (HR 0.50, 95% CI: 0.26-0.96, p=.037). CONCLUSION: One year after presenting for
      EC, women choosing the copper IUD for EC were half as likely to have a pregnancy
      compared to those choosing oral LNG. IMPLICATIONS: Compared to EC users who
      choose oral levonorgestrel, those who select the copper IUD have lower rates of
      pregnancy in the next year. Greater use of the copper IUD for EC may lower rates
      of unintended pregnancy in high-risk women.

PMID- 24332434
TI  - Abortion barriers and perceptions of gestational age among women seeking abortion
      care in the latter half of the second trimester.
AB  - OBJECTIVE: Later second-trimester abortion (gestational age >= 19 weeks) is
      higher risk, more expensive and more difficult to access than abortion earlier in
      pregnancy. We sought to enumerate barriers to care described by women seeking
      abortion in the latter half of the second trimester. We also assessed the
      accuracy of later second-trimester abortion patients' perceptions of their
      pregnancies' gestational ages. STUDY DESIGN: A retrospective analysis of data
      from 232 women served by a referral program for women seeking abortion care
      between 19 and 24 weeks of gestational age was performed. Data collected included
      demographics, pregnancy history, gestational age by ultrasound, perceived
      gestational age, barriers to abortion care experienced and time lapsed from
      pregnancy recognition to presentation for care. RESULTS: Difficulty deciding
      whether to terminate (44.8%), financial barriers to care (22.0%) and the patient
      having recently realized she was pregnant (21.6%) were the most common delaying
      barriers cited. Nearly half (46.6%) of women underestimated their own gestational
      ages by greater than 4 weeks. Risk factors for experiencing at least 3 months
      time lapsed from pregnancy recognition to program referral included difficulty
      deciding whether to terminate [odds ratio (OR) 4.08, 95% confidence interval (CI)
      2.51-8.70] and nonwhite race/ethnicity (OR 2.04, 95% CI 1.16-3.57). CONCLUSIONS:
      Women seeking abortion care in the latter half of the second trimester encounter
      many of the same barriers previously identified among other abortion patient
      populations. Because many risk factors for delayed presentation for care are not
      amenable to intervention, abortion must remain available later in the second
      trimester. IMPLICATIONS: Women presenting for abortion in the later second
      trimester are delayed by structural and individual-level barriers, and many
      substantially underestimate their own gestational age. Removing financial
      barriers may help reduce abortion delay; however, many risk factors are
      nonmodifiable, underscoring the need to ensure access to later second-trimester
      abortion.

PMID- 24332435
TI  - Health hazards and medical treatment of volunteers aged 18-30 years working in
      international social projects of non-governmental organizations (NGO).
AB  - The specific health risk profile and diversity of treatments sought by young
      volunteers participating in international social projects should differ from
      those of their older colleagues. In the absence of any data to identify whether
      this was correct, a retrospective analysis was performed using a standardized
      questionnaire. Questions included what diseases occurred, and details of the
      frequency and types of treatment sought during their stay - (e.g. self-treatment,
      medical/dental intervention, or local healer). The 153 participants were aged 18
      30 years and worked in a non-governmental organization for >6 months. The
      participants were: 53% female, mean age 20 years, and mean duration of stay was
      11.2 months. Their NGO placement abroad was in Latin America 65.4%, 14.4% in
      Africa, and 9.8% in Asia. 83% of the young volunteers had received some advice
      regarding travel medicine before their departure. However, they suffered from
      more injuries compared to private travellers, and febrile infections were more
      common when compared to older studies. 21.2% suffered from dental problems and
      50% of them sought medical treatment. This study highlights a previously
      unreported higher risk profile of specific health problems occurring in young NGO
      volunteers, including some potentially life-threatening diagnoses that differed
      from their older colleagues and normal travellers. It is recommended that young
      volunteers should receive age specific, comprehensive pre-departure training in
      health and safety, first aid, and management of common health problems. A medical
      check-up upon returning home should be mandatory. The provision of a basic first
      aid kit to each volunteer before departure is also recommended. 

PMID- 24332436
TI  - Sexuality in burn victims: an integrative literature review.
AB  - AIMS: To analyze and synthesize knowledge concerning sexuality in adult burn
      victims through an integrative literature review. METHOD: Two researchers
      independently searched six electronic databases (PUBMED, LILACS, ISI Web of
      Science, PSYCINFO, CINAHL and EMBASE) and also performed a hand search using the
      following descriptors, in different combinations: burn, sexuality, gender
      identity, sexual behavior and sexual factors, in order to identify the articles
      published in English, Portuguese or Spanish, in the last 20 years. A total of
      1781 articles were found and 22 were selected based on the inclusion and
      exclusion criteria. RESULTS: The findings were organized into two categories that
      influence sexuality: (1) studies where the main purpose was to assess sexuality
      in burn victims; (2) studies that indirectly assess sexuality. CONCLUSION: The
      synthesis of the knowledge concerning sexuality in burn victims showed that
      sexual dysfunction can be related to the younger ages, TBSA > 20%, burns on the
      genitalia and on exposed areas, prolonged length of hospital stay, avoidance
      coping, and mental disorders. The multidisciplinary team should be prepared to
      integrate sexuality as an important variable in the continuing treatment of burn
      patients.

PMID- 24332437
TI  - Butter for burns or for bread?: A dilemma.

PMID- 24332438
TI  - Hydrotherapy in burn care: a survey of hydrotherapy practices in the UK and
      Ireland and literature review.
AB  - INTRODUCTION: Hydrotherapy is widely used in burns management however there are
      risks associated with its use, in particular cross-infection. Data regarding
      indications and techniques in common use is deficient. This study aimed to
      investigate hydrotherapy practices in the UK and Ireland. METHODS: A survey of
      the hydrotherapy practice of major burn care providers was performed by e mail
      and where necessary, follow up telephone contact. RESULTS: The survey included 28
      burn care providers. 27 reported using hydrotherapy. Only 11 (41%) had defined
      indication criteria with 4 (15%) implementing a specific protocol. Variations in
      hydrotherapy practice were seen. CONCLUSION: Hydrotherapy is used nationwide,
      however considerable variation in practice exists. One area worthy of further
      consideration is the need for appropriate standards of infection control.

PMID- 24332439
TI  - "Modernized standards in burns management: a comparative study in Komfo Anokye
      Teaching Hospital, Kumasi, Ghana" and I have some opinions about it.

PMID- 24332440
TI  - External wire-frame fixation of digital skin grafts: a non-invasive alternative
      to the K-wire insertion method.
AB  - BACKGROUND AND AIM: The current skin graft fixation methods for digits, including
      the Kirschner wire insertion technique, can be limited by inadequate or excessive
      fixation and complications such as infection or secondary injuries. Therefore,
      the external wire-frame fixation method was invented and used for skin grafting
      of digits. This study aimed to investigate external wire-frame fixation of
      digital skin grafts as a non-invasive alternative to the K-wire insertion method.
      METHODS: In 2005-2012, 15 patients with burn scar contractures on the hand digits
      received a skin graft that was then fixed with an external wire frame. The intra
      operative time needed to make the wire frame, the postoperative time to frame and
      suture removal, the graft survival rate, the effect of contracture release and
      the complications were recorded. RESULTS: In all cases, the contracture release
      was 100%. The complete graft survival rate was 98.6%. Four patients had
      epithelial necrosis in <5% of the total area. There were no other complications
      such as pressure ulcer or hypoxia of fingers. CONCLUSIONS: External wire-frame
      fixation is simple, minimally invasive and a custom-made technique for skin
      grafting of the fingers. It was designed for its potential benefits and the
      decreased risk it poses to patients with scar contractures on their fingers. It
      can be implemented in three phases of grafting, does not affect the epiphyseal
      line or subsequent finger growth and is suitable for children with multi-digit
      involvement.

PMID- 24332441
TI  - Real-time 3D interactive segmentation of echocardiographic data through user
      based deformation of B-spline explicit active surfaces.
AB  - Image segmentation is an ubiquitous task in medical image analysis, which is
      required to estimate morphological or functional properties of given anatomical
      targets. While automatic processing is highly desirable, image segmentation
      remains to date a supervised process in daily clinical practice. Indeed,
      challenging data often requires user interaction to capture the required level of
      anatomical detail. To optimize the analysis of 3D images, the user should be able
      to efficiently interact with the result of any segmentation algorithm to correct
      any possible disagreement. Building on a previously developed real-time 3D
      segmentation algorithm, we propose in the present work an extension towards an
      interactive application where user information can be used online to steer the
      segmentation result. This enables a synergistic collaboration between the
      operator and the underlying segmentation algorithm, thus contributing to higher
      segmentation accuracy, while keeping total analysis time competitive. To this
      end, we formalize the user interaction paradigm using a geometrical approach,
      where the user input is mapped to a non-cartesian space while this information is
      used to drive the boundary towards the position provided by the user.
      Additionally, we propose a shape regularization term which improves the
      interaction with the segmented surface, thereby making the interactive
      segmentation process less cumbersome. The resulting algorithm offers competitive
      performance both in terms of segmentation accuracy, as well as in terms of total
      analysis time. This contributes to a more efficient use of the existing
      segmentation tools in daily clinical practice. Furthermore, it compares favorably
      to state-of-the-art interactive segmentation software based on a 3D livewire
      based algorithm. 

PMID- 24332442
TI  - Automatic detection and quantification of brain midline shift using anatomical
      marker model.
AB  - Brain midline shift (MLS) is a significant factor in brain CT diagnosis. In this
      paper, we present a new method of automatically detecting and quantifying brain
      midline shift in traumatic injury brain CT images. The proposed method
      automatically picks out the CT slice on which midline shift can be observed most
      clearly and uses automatically detected anatomical markers to delineate the
      deformed midline and quantify the shift. For each anatomical marker, the detector
      generates five candidate points. Then the best candidate for each marker is
      selected based on the statistical distribution of features characterizing the
      spatial relationships among the markers. Experiments show that the proposed
      method outperforms previous methods, especially in the cases of large intra
      cerebral hemorrhage and missing ventricles. A brain CT retrieval system is also
      developed based on the brain midline shift quantification results. 

PMID- 24332443
TI  - [Prior health advice to immigrants who travel to visit family and friends].
AB  - OBJECTIVE: Immigrants who make or plan journeys to visit their families in their
      countries of origin (immigrants -visiting friends and relatives, I-VFR) have a
      higher risk of acquiring travel-associated diseases than other travellers. The
      main aim of this study is to analyse the knowledge of the immigrant population on
      the need to receive health advice (HA) before making international journeys in
      general and in particular before travelling to their country of origin. DESIGN:
      Observational, multicentre study. SETTING: Ten Family Doctors from 10 Health
      Centres in Catalonia and Aragon participated PARTICIPANTS: A total of 555
      immigrants >= 15 years of age, who consulted their Family Doctor and agreed to
      answer a questionnaire. Opportunity sampling was used. RESULTS: A total of 389
      (70.1%) of those surveyed considered it necessary to receive HA before making an
      international journey, 406 (73.2%) were I-VFR and 145 (35.7%) had requested HA
      prior to the journey, mostly from their Family Doctor (n=60; 41.1%). Almost two
      thirds (261, 65.2%) of the subjects did not seek HA, with the most common reason
      being that they did not consider it necessary (173, 42.6%). CONCLUSIONS: I-VFR do
      not usually request HA prior to travelling, basic due to considering it
      unnecessary. When they do request it, they are very often initially directed to
      their Family Doctor.

PMID- 24332444
TI  - [Increasing participation of primary care in the management of people with human
      immunodeficiency virus: hospital care professionals express their views].
AB  - AIM: To determine the opinions of infectious diseases professionals on the
      possibilities of monitoring patients with HIV in Primary Care. DESIGN:
      Qualitative study using in-depth interviews. LOCATION: Infectious Diseases Unit
      in the University Hospital "Virgen de la Victoria" in Malaga. PARTICIPANTS:
      Health professionals with more than one year experience working in infectious
      diseases. A total of 25 respondents: 5 doctors, 15 nurses and 5 nursing
      assistants. METHOD: Convenience sample. Semi-structured interviews were used that
      were later transcribed verbatim. Content analysis was performed according to the
      Taylor and Bogdan approach with computer support. Validation of information was
      made through additional analysis, expert participation, and feedback of part of
      the results to the participants. RESULTS: Hospital care professionals considered
      the disease-related complexity of HIV, treatment and social aspects that may have
      an effect on the organizational level of care. Professionals highlighted the
      benefits of specialized care, although opinions differed between doctors and
      nurses as regards follow up in Primary Care. Some concerns emerged about the
      level of training, confidentiality and workload in Primary Care, although they
      mentioned potential advantages related to accessibility of patients. CONCLUSIONS:
      Physicians perceive difficulties in following up HIV patients in Primary Care,
      even for those patients with a good control of their disease. Nurses and nursing
      assistants are more open to this possibility due to the proximity to home and
      health promotion in Primary Care.

PMID- 24332445
TI  - [Observational and cross-sectional study of prevalence and severity of the opioid
      induced bowel dysfunction].
AB  - OBJECTIVE: To analyze the prevalence and severity of the opioid-induced bowel
      dysfunction (OBD) symptoms. DESIGN: Epidemiological, observational and cross
      sectional study. LOCATION: Six Spanish centers participated. PARTICIPANTS: A
      total of 317 outpatients with a diagnosis of cancer pain or non-cancer pain
      treated with a unique opioid were recruited. MAIN MEASUREMENTS: The prevalence of
      OBD symptoms was measured using a visual analog scale (VAS: 0-100), and
      constipation was also assessed by the Bowel Function Index (BFI). The treatment
      for gastrointestinal symptoms was recorded, and the frequency of symptoms between
      different opioid treatments was compared. Finally, quality of life was evaluated.
      RESULTS: The prevalence of OBD with at least one gastrointestinal disorder was
      94.6%, with constipation being the most frequent symptom (BFI: 91.6%; VAS: 90.2%)
      and nearly half of the patients showed three or more symptoms with a VAS >= 4. No
      significant differences were detected in the prevalence of symptoms between the
      opioid groups. A decrease in the wellbeing of patients was detected related to
      moderate to severe gastrointestinal symptoms. CONCLUSIONS: A high rate of
      gastrointestinal disorders probably related to OBD have been confirmed in
      patients on opioid therapy, highlighting the need for new drug strategies.

PMID- 24332446
TI  - Lack of visual evoked potentials amplitude decrement during prolonged reversal
      and motion stimulation in migraineurs.
AB  - OBJECTIVE: We evaluated response decrement during a short time repetitive low and
      high contrast reversal and low contrast motion stimulation in controls and
      migraineurs. METHODS: A total of 39 migraine patients (out of which 19 were in
      the interictal period and without prophylactic treatment) and 36 healthy
      volunteers were examined using pattern-reversal (PR-VEP) and motion-onset (M-VEP)
      visual evoked potentials. Binocular stimulation lasted 2.5 min and the decrement
      assessment was blinded. RESULTS: Evidence of significant decrement was observed
      in healthy volunteers for high contrast PR-VEP amplitude of P100-N75 ratios
      between the fifth and first blocks (0.9; p=0.001) with a linear decline (-0.7
      MUV/min, p=0.001) and in the P100-N145 amplitude with linear decline (-0.5
      MUV/min, p=0.004). Significant decrement was also observed for the ratio between
      the fifth and first block P1-N2 amplitudes in M-VEP (0.9, p=0.006). No
      significant decrement was noted in the low contrast PR-VEP or among migraineurs.
      CONCLUSIONS: We confirm differences in decrease of VEPs amplitude during short
      term examination between controls and migraineurs. We showed the decrement
      deficit also in the extrastriatal regions of the migraineurs' visual cortex.
      SIGNIFICANCE: Low contrast and motion-onset stimuli in short time decrement
      assessment did not increase the test sensitivity.

PMID- 24332447
TI  - Can topical duloxetine be used for neuropathic pain?
AB  - Duloxetine is a serotonin and norepinephrine re-uptake inhibitor with both anti
      depressant and pain-relieving properties. Its pain-relieving properties are due
      to its action on the descending inhibitory pain pathways. However, the fast onset
      of analgesia may be mediated by mechanisms other than the descending inhibitory
      pain pathways. This study posits the hypothesis that duloxetine may have pain
      relieving property by peripheral analgesic effects. Ways of testing this
      hypothesis and its potential topical use are discussed. 

PMID- 24332448
TI  - Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the
      treatment of Alzheimer's disease.
AB  - Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a
      plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a
      nutraceutical in the United States. In addition to acting as an
      acetylcholinesterase inhibitor, HupA possesses neuroprotective properties.
      However, the relevant mechanism is unknown. Here, we showed that the
      neuroprotective effect of HupA was derived from a novel action on brain iron
      regulation. HupA treatment reduced insoluble and soluble beta amyloid levels,
      ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex
      and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta
      amyloid oligomers and amyloid precursor protein levels, and increased A
      Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD
      mice. However, these beneficial effects of HupA were largely abolished by feeding
      the animals with a high iron diet. In parallel, we found that HupA decreased iron
      content in the brain and demonstrated that HupA also has a role to reduce the
      expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake
      in cultured neurons. The findings implied that reducing iron in the brain is a
      novel mechanism of HupA in the treatment of Alzheimer's disease. 

PMID- 24332450
TI  - A novel panel of biomarkers predicts radioresistance in patients with squamous
      cell carcinoma of the head and neck.
AB  - PURPOSE: Global gene expression analysis was performed on pre-treatment biopsies
      from patients with squamous cell carcinoma of the head and neck (SCCHN) to
      discover biomarkers that can predict outcome of radiation based therapy. METHODS:
      We initially evaluated RNA expression using cDNA microarray analysis of 38
      patients that received radiotherapy (RT). The five strongest candidates (VEGF,
      BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies
      in a second group of 86 patients who received radiation based treatment using
      immunohistochemical staining (IHC), prepared by tissue microarray. RESULTS: In
      the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT.
      cDNA microarrays revealed 60 genes that were linked to response to therapy. In
      the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause
      specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and
      90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR
      were increased expression of vascular endothelial growth factor (VEGF) (p=0.02),
      Yes-associated protein (YAP-1) (p<0.01), CLAUDIN-4 (p<0.01), c-MET (p<0.01) and
      BCL-2 (p=0.02). Biomarkers predictive of poor RFS were YAP-1 (p=0.01) and BCL-2
      (p<0.01). Biomarkers predictive of poor CSS were YAP-1 (p=0.04), VEGF (p=0.03)
      and CLAUDIN-4 (p=0.03). Furthermore, when YAP-1 and c-MET expression levels were
      combined the prediction of radio-resistance was increased. CONCLUSION: All five
      biomarkers were predictive of poor response to radiation based therapy. In
      particular, YAP-1 and c-MET have synergistic power and could be used to make
      treatment decisions.

PMID- 24332449
TI  - Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5
      expression in the cerebellum of fragile X mental retardation gene 1 premutation
      carriers with fragile X-associated tremor/ataxia syndrome.
AB  - A premutation (PM) expansion (55-200 CGG) in the fragile X mental retardation
      gene 1 causes elevated messenger RNA and reduced fragile X mental retardation
      gene 1 protein. Young PM carriers can develop characteristic physical features
      and mild cognitive disabilities. In addition, individuals with PM, particularly
      male carriers, are at high risk to develop fragile X-associated tremor/ataxia
      syndrome (FXTAS) with aging. Human postmortem FXTAS brains show extensive white
      matter disease in the cerebellum and the presence of intranuclear inclusions
      throughout the brain, although their etiologic significance is unknown. In the
      current work, expression levels of the metabotropic glutamate (Glu) receptor 5
      and the Glu transporter excitatory amino acid transporter 1, examined by reverse
      transcription polymerase chain reaction and western blot analyses, were found to
      be reduced in the postmortem cerebellum of PM carriers with FXTAS compared with
      age matched controls, with higher CGG repeat number having greater reductions in
      both proteins. These data suggests a dysregulation of Glu signaling in PM
      carriers, which would likely contribute to the development and severity of FXTAS.

PMID- 24332451
TI  - Relationship between everolimus exposure and safety and efficacy: meta-analysis
      of clinical trials in oncology.
AB  - BACKGROUND: In patients with solid tumours, daily everolimus dosing demonstrated
      dose proportionality and linear pharmacokinetics. A meta-analysis was conducted
      to characterise the relationship between everolimus Cmin and efficacy and safety
      and the effect of CYP3A4 and P-glycoprotein (PgP) substrate/inhibitor/inducer
      coadministration on everolimus trough concentration (Cmin). METHODS: Individual
      patient data from five phase 2/3 studies, in which steady state, predose
      pharmacokinetic samples were taken from patients with solid tumours administered
      everolimus 10mg/day, were pooled. FINDINGS: Efficacy and safety were evaluable
      for 945 and 938 patients, respectively. A 2-fold increase in everolimus Cmin
      increased the likelihood of tumour size reduction (odds ratio 1.40, 95%
      confidence interval (CI) 1.23-1.60), was associated with a trend for reduced risk
      of progression-free survival events (risk ratio [RR] 0.90, 95% CI 0.69-1.18) and
      increased the risk of grade ?3 pulmonary (RR 1.93, 95% CI 1.12-3.34), stomatitis
      (RR 1.49, 95% CI 1.05-2.10) and metabolic (RR 1.30, 95% CI 1.02-1.65) events.
      Coadministering everolimus with strong CYP3A4 and PgP inhibitors increased
      everolimus Cmin by 10% and 20%, respectively; coadministration with CYP3A4
      inducers reduced Cmin by 7%. INTERPRETATION: A 2-fold increase in everolimus Cmin
      was associated with improved tumour size reduction and increased risk of high
      grade pulmonary, metabolic and stomatitis events. FUNDING: Novartis
      Pharmaceuticals Corporation.

PMID- 24332452
TI  - Hospital-associated venous thromboembolism in children: incidence and clinical
      characteristics.
AB  - OBJECTIVE: To determine incidence and clinical characteristics of hospital
      associated venous thromboembolism (VTE) in pediatric patients. STUDY DESIGN: A
      retrospective analysis of patients with hospital-associated VTE at the Johns
      Hopkins Hospital from 1994 to 2009 was performed. Clinical characteristics of
      patients aged 21 years and younger who developed VTE symptoms after 2 days of
      hospitalization or <90 days after hospital discharge were examined. International
      Classification of Diseases, Ninth Revision codes were used to categorize patients
      with complex chronic medical conditions and trauma. RESULTS: There were 270
      episodes of hospital-associated VTE in 90,485 admissions (rate 30 per 10,000
      admissions). Young adults (18-21 years) and adolescents (14-17 years) had
      significantly increased rates of VTE compared with children (2-9 years)
      (incidence rate ratio [IRR] 7.7, 95% CI 5.1-12.0; IRR 4.3, 95% CI 2.7-6.8,
      respectively). A central venous catheter (CVC) was present in 50% of patients,
      and a surgical procedure was performed in 45% of patients before VTE diagnosis.
      For patients without a CVC, trauma was the most common admitting diagnosis. CVC
      related VTE was diagnosed most frequently in infants (<1 year old) and in
      patients with malignancy. Renal and cardiac diseases were associated with the
      highest rates of VTE (51 and 48 per 10,000, respectively). Rates were
      significantly higher among those with >= 4 medical conditions compared with those
      with 1 medical condition (IRR 4.0, 95% CI 1.4-8.9). CONCLUSION: Older age and
      multiple medical conditions were associated with increased rates of hospital
      associated VTE. These data can contribute to the design of future clinical trials
      to prevent hospital-associated VTE in high-risk children.

PMID- 24332454
TI  - Not all myoclonic jerking and tonic posturing in the neonate is epilepsy.

PMID- 24332455
TI  - Violent conflict and opiate use in low and middle-income countries: a systematic
      review.
AB  - BACKGROUND: Violent conflicts disproportionately affect populations in low and
      middle-income countries, and exposure to conflict is a known risk factor for
      mental disorders and substance use, including use of illicit opiates. Opiate use
      can be particularly problematic in resource-limited settings because few
      treatment options are available and dependence can impede economic development.
      In this systematic review, we explore the relationship between violent conflict
      and opiate use in conflict-affected populations in low and middle-income
      countries. METHODS: We searched MEDLINE, PsychINFO, SCOPUS, PILOTS, and select
      grey literature databases using a defined list of key terms related to conflict
      and opiate use, screened the results for relevant and methodologically rigorous
      studies, and conducted a forward search of the bibliographies of selected results
      to identify additional studies. RESULTS: We screened 707 articles, selecting 6
      articles for inclusion: 4 quantitative studies and 2 qualitative studies that
      examined populations in 9 different countries. All study participants were adults
      (aged 15-65) living in or displaced from a conflict-affected country. Data
      sources included death records, hospital records, and interviews with refugees,
      internally displaced persons, and others affected by conflict. Overall, we found
      a positive, but ambiguous, association between violent conflict and opiate use,
      with five of six studies suggesting that opiate use increases with violent
      conflict. Five key factors mediate the conceptual relationship between opiate use
      and violent conflict: (1) pre-conflict opiate presence, (2) mental disorders, (3)
      lack of economic opportunity, (4) changes in social norms or structure, and (5)
      changes in drug availability. CONCLUSIONS: The strength and direction of the
      association between opiate use and violent conflict and the proposed mediating
      factors may differ between contexts, necessitating country and population
      specific research and interventions. Prevalence of opiate use prior to the start
      of conflict was common to all populations in which conflict induced a change in
      opiate use, suggesting that interventions to reduce opiate use and future
      research should focus on such populations. Population-based, longitudinal studies
      that use systematic measures of exposure to conflict and opiate use are needed to
      further explore this association and its mediating factors.

PMID- 24332453
TI  - An approach to the identification of anomalies and etiologies in neonates with
      identified or suspected VACTERL (vertebral defects, anal atresia, tracheo
      esophageal fistula with esophageal atresia, cardiac anomalies, renal anomalies,
      and limb anomalies) association.

PMID- 24332456
TI  - Public opinion of drug treatment policy: exploring the public's attitudes,
      knowledge, experience and willingness to pay for drug treatment strategies.
AB  - BACKGROUND: Research evidence is strong for opiate replacement treatment (ORT).
      However, public opinion (attitudes) can be at odds with evidence. This study
      explored the relationships between, attitudes, knowledge of drugs and a range of
      socio-demographic variables that potentially influence attitude. This is relevant
      in the current policy arena in which a major shift from harm reduction to,
      rehabilitation is underway. METHODS: A cross sectional postal questionnaire
      survey in Scotland was conducted where the drug, treatment strategy has changed
      from harm-reduction to recovery-based. A random sample (N=3000), of the general
      public, >18 years, and on the electoral register was used. The questionnaire was
      largely structured with tick box format but included two open questions for
      qualitative responses. Valuation was measured using the economic willingness-to
      pay (WTP) method. RESULTS: The response rate was 38.1% (1067/2803). Less than 10%
      had personal experience of drug, misuse but 16.7% had experience of drug misuse
      via a friend/acquaintance. Regression modelling revealed more positive attitudes
      towards drug users in those with personal experience of drug misuse, (p<0.001),
      better knowledge of drugs (p=0.001) and higher income (those earning >L50,000
      per, annum compared to <L15K; p=0.01). Over half of respondents were not willing
      to pay anything for drug treatment indicating they did not value these treatments
      at all. Respondents were willing-to-pay most for community rehabilitation and
      least for methadone maintenance treatment. Qualitative analysis of open responses
      indicated many strong negative attitudes, doubts over the efficacy of methadone
      and consideration of addiction as self-inflicted. There was ambivalence with
      respondents weighing up negative feelings towards treatment against societal
      benefit. CONCLUSIONS: There is a gap between public attitudes and evidence
      regarding drug treatment. Findings suggest a way forward might be to develop and
      evaluate treatment that integrates ORT with a community rehabilitative approach.
      Evaluation of public engagement/education to improve knowledge of drug treatment
      effectiveness is recommended.

PMID- 24332457
TI  - Views and experiences of hepatitis C testing and diagnosis among people who
      inject drugs: systematic review of qualitative research.
AB  - BACKGROUND: Many developed countries are facing a major challenge to improve
      identification of individuals acutely and chronically infected with hepatitis C
      virus (HCV) infection. We explored the views and experiences of people who inject
      drugs (PWID) in relation to HCV testing, and diagnosis through a review and
      synthesis of qualitative research. METHODS: Based on the thematic synthesis of
      qualitative research. Searches were conducted in 14 databases and supplemented by
      reference checking, hand searching of selected journals, and searches of relevant
      websites. Studies of any qualitative design that examined the views and
      experiences of, and attitudes towards, HCV testing and diagnosis among PWID or
      practitioners involved in their care were included. Key themes and sub-themes
      were systematically coded according to the meaning and content of the findings of
      each study which proceeded to the preparation of a narrative account of the
      synthesis. RESULTS: 28 qualitative studies were identified. We identified a
      number of overarching descriptive themes in the literature, finding overall that
      PWID hold complex and differing views and experiences of testing and diagnosis.
      Three major themes emerged: missed opportunities for the provision of information
      and knowledge; shifting priorities between HCV testing and other needs; and
      testing as unexpected and routine. Evidence of missed opportunities for the
      provision of knowledge and information about HCV were clear, contributing to
      delays in seeking testing and providing a context to poor experiences of
      diagnosis. Influenced by the nature of their personal circumstances, perceptions
      of the risk associated with HCV and the prioritisation of other needs acted both
      to encourage and discourage the uptake of HCV testing. Undergoing HCV testing as
      part of routine health assessment, and an unawareness of being testing was
      common. An unexpected positive diagnosis exacerbated anxiety and confusion.
      CONCLUSION: This review has identified that there are modifiable factors that
      affect the uptake of HCV testing and experiences of HCV diagnosis among PWID.
      Intervention development should focus on addressing these factors. There is a
      need for further research that engages PWID from a diverse range of populations
      to identify interventions, strategies and approaches that they consider valuable.

PMID- 24332458
TI  - Experiences with urine drug testing by police among people who inject drugs in
      Bangkok, Thailand.
AB  - BACKGROUND: Thailand has relied on drug law enforcement in an effort to curb
      illicit drug use. While anecdotal reports suggest that Thai police frequently use
      urine toxicology to identify drug users, little is known about the prevalence or
      impacts of this practice among people who inject drugs (IDU). Therefore, we
      sought to examine experiences with urine drug testing by police among IDU in
      Bangkok. METHODS: Data were derived from a community-recruited sample of IDU in
      Bangkok participating in the Mitsampan Community Research Project between July
      and October 2011. We assessed the prevalence and correlates of being subjected to
      urine toxicology testing by police using multivariate Poisson regression.
      RESULTS: In total, 438 IDU participated in this study, with 293 (66.9%)
      participants reporting having been tested for illicit drugs by police. In
      multivariate analyses, reports of drug testing by police were independently and
      positively associated with younger age (adjusted prevalence ratio [APR]: 1.28), a
      history of methamphetamine injection (APR: 1.22), a history of incarceration
      (APR: 1.21), having been in compulsory drug detention (APR: 1.43), avoiding
      healthcare (APR: 1.15), and HIV seropositivity (APR: 1.19), and negatively
      associated with access to voluntary drug treatment (APR: 0.82) (all p<0.05).
      CONCLUSION: A high proportion of IDU in Bangkok were subjected to drug testing by
      police. Young people and methamphetamine injectors were more likely to have been
      tested. The findings indicate that drug testing by police is associated with the
      compulsory drug detention system and may be interfering with IDU's access to
      healthcare and voluntary drug treatment. These findings raise concern about the
      widespread practice of drug testing by police and its associated impacts.

PMID- 24332459
TI  - Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21
      inhibitor and doxorubicin to treat glioma.
AB  - The combined treatment of chemotherapeutant and microRNA (miR) has been proven to
      be a viable strategy for enhancing chemosensitivity due to its synergistic effect
      for tumor therapy. However, the co-delivery of drugs and genes remains a major
      challenge as they lack efficient co-delivery carriers. In this study, three
      amphiphilic star-branched copolymers comprising polylactic acid (PLA) and
      polydimethylaminoethyl methacrylate (PDMAEMA) with AB3, (AB3)2,and (AB3)3
      molecular architectures were synthesized respectively by a combination of ring
      opening polymerization, atom transfer radical polymerization, and click chemistry
      via an "arm-first" approach. The star copolymers possessed a low critical micelle
      concentration (CMC) and formed nano-sized micelles with positive surface charges
      in water as well as exhibiting a much lower cytotoxicity than PEI 25 kDa.
      Nevertheless, their gene transfection efficiency and tumor inhibition ability
      showed a remarkable dependence on their molecular architecture. The (AB3)3
      architecture micelle copolymer exhibited the highest transfection efficiency,
      about 2.5 times higher than PEI. In addition, after co-delivering DOX and miR-21
      inhibitor (miR-21i) into LN229 glioma cells, the micelles could mediate escaping
      miR-21i from lysosome degradation and the release of DOX to the nucleus, which
      significantly decreased the miR-21 expression. Moreover, co-delivery of DOX and
      miR-21i surprisingly exhibited an anti-proliferative efficiency compared with DOX
      or the miR-21i treatment alone. These results demonstrated that amphiphilic star
      branched copolymers are highly promising for their combinatorial delivery of
      genes and hydrophobic therapeutants.

PMID- 24332461
TI  - Low molecular weight fluorescent probes with good photostability for imaging RNA
      rich nucleolus and RNA in cytoplasm in living cells.
AB  - We have synthesized two low molecular weight organic molecules, PY and IN
      successfully, which selectively stain nucleolus and cytoplasm of living cells in
      30 min, with a much lower uptake in the nucleus. Nucleic acids electrophoresis
      and digest test of ribonuclease indicate their markedly higher affinity for RNA,
      especially PY. Moreover their RNA localization in cells is further supported by
      digest test of ribonuclease, namely, the nucleolar fluorescence signal is
      distinctly lost upon treatment with RNase. And, the fact that live cells stained
      by PY and IN still possess physiological function can be confirmed: 1) MTT assay
      demonstrates that the mitochondria of cells stained remains its electron
      mediating ability, 2) Double assay of PY/IN and propidium iodide as well as
      trypan blue testing show that the membrane of cells stained still is intact.
      Importantly, compared with the only commercial RNA probe, SYTO RNA-Select, PY and
      IN exhibit much better photostability when continuously illuminated with 488 nm
      laser and mercury lamp. These results prove that PY and IN are very attractive
      staining reagents for visualizing RNA in living cells.

PMID- 24332460
TI  - Neuroprotective ferulic acid (FA)-glycol chitosan (GC) nanoparticles for
      functional restoration of traumatically injured spinal cord.
AB  - An urgent unmet need exists for early-stage treatment of spinal cord injury
      (SCI). Currently methylprednisolone is the only therapeutic agent used in
      clinics, for which the efficacy is controversial and the side effect is well
      known. We demonstrated functional restoration of injured spinal cord by self
      assembled nanoparticles composed of ferulic acid modified glycol chitosan (FA
      GC). Chitosan and ferulic acid are strong neuroprotective agents but their
      systemic delivery is difficult. Our data has shown a prolonged circulation time
      of the FA-GC nanoparticles allowing for effective delivery of both chitosan and
      ferulic acid to the injured site. Furthermore, the nanoparticles were found both
      in the gray matter and white matter. The in vitro tests demonstrated that
      nanoparticles protected primary neurons from glutamate-induced excitotoxicity.
      Using a spinal cord contusion injury model, significant recovery in locomotor
      function was observed in rats that were intravenously administered nanoparticles
      at 2 h post injury, as compared to non-improvement by methylprednisolone
      administration. Histological analysis revealed that FA-GC treatment significantly
      preserved axons and myelin and also reduced cavity volume, astrogliosis, and
      inflammatory response at the lesion site. No obvious adverse effects of
      nanoparticles to other organs were found. The restorative effect of FA-GC
      presents a promising potential for treating human SCIs.

PMID- 24332462
TI  - Coordinate transformation based cryo-correlative methods for electron tomography
      and focused ion beam milling.
AB  - Correlative microscopy allows imaging of the same feature over multiple length
      scales, combining light microscopy with high resolution information provided by
      electron microscopy. We demonstrate two procedures for coordinate transformation
      based correlative microscopy of vitrified biological samples applicable to
      different imaging modes. The first procedure aims at navigating cryo-electron
      tomography to cellular regions identified by fluorescent labels. The second
      procedure, allowing navigation of focused ion beam milling to fluorescently
      labeled molecules, is based on the introduction of an intermediate scanning
      electron microscopy imaging step to overcome the large difference between cryo
      light microscopy and focused ion beam imaging modes. These methods make it
      possible to image fluorescently labeled macromolecular complexes in their natural
      environments by cryo-electron tomography, while minimizing exposure to the
      electron beam during the search for features of interest. 

PMID- 24332463
TI  - Economic stress in childhood and adulthood, and poor psychological health: three
      life course hypotheses.
AB  - Investigations of mental health in a life course perspective are scarce. The aim
      is to investigate associations between economic stress in childhood and
      adulthood, and poor psychological health in adulthood with reference to the
      accumulation, critical period and social mobility hypotheses in life course
      epidemiology. The 2008 public health survey in Skane is a cross-sectional postal
      questionnaire study. A random sample was invited which yielded 28,198 respondents
      aged 18-80 (55% participation). Psychological health was assessed with the GHQ12
      instrument. Logistic regression models were used to investigate the associations
      adjusting for age, country of birth, socioeconomic status, emotional support,
      instrumental support and trust, and stratifying by sex. The accumulation
      hypothesis was confirmed because combined childhood and adulthood exposures to
      economic stress were associated with poor psychological health in a graded
      manner. The social mobility hypothesis was also confirmed. The critical period
      hypothesis was not confirmed because both childhood and adulthood economic stress
      remained significantly associated with poor psychological health in adulthood.
      Economic stress in childhood is associated with mental health in adulthood. 

PMID- 24332464
TI  - Differences of bone healing in metaphyseal defect fractures between osteoporotic
      and physiological bone in rats.
AB  - Discrepancies in bone healing between osteoporotic and non-osteoporotic bone
      remain uncertain. The focus of the current work is to evaluate potential healing
      discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley
      rats were either ovariectomized (OVX, n=14) and combined with a calcium-,
      phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM
      operation with standard diet rat (SHAM, n=14). Three months post-ovariectomy,
      DEXA measurement showed a reduction of bone mineral density reflecting an
      osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped
      osteotomy at the distal metaphyseal area of the left femur stabilized with a T
      shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by
      means of a non-destructive three-point bending test showed significant lower
      flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals
      (p=0.048) but no differences at 10 mm lever span. Microcomputer tomography (MUCT)
      showed bridging cortices and consolidation of the defect in both groups, however,
      no measurable differences were found in either total ossified tissue or vascular
      volume fraction. Furthermore, histology showed healing discrepancies that were
      characterized by cartilaginous remnant and more unmineralized tissue presence in
      the OVX rats compared to more mature consolidation appearance in the SHAM group.
      In summary, bone defect healing in metaphyseal bone slightly differs between
      osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both
      3mm lever span biomechanical testing and histology.

PMID- 24332465
TI  - Reduction in mortality in severely injured patients following the introduction of
      the "Treatment of patients with severe and multiple injuries" guideline of the
      German society of trauma surgery--a retrospective analysis of a level 1 trauma
      center (2010-2012).
AB  - OBJECTIVE: The German society of trauma surgery published the "Treatment of
      Patients with Severe and Multiple injuries" guideline in 2011. This achieved the
      highest level of recommendation for guidelines published in Germany. This study
      investigated if there was an improvement in the survival rates of severed injured
      patients following the introduction of the guideline in clinical treatment.
      METHODS: All patients with an injury severity score >=16 on primary admission to
      hospital between January 2010 and December 2012 (a total of 373 patients) were
      included in this study. The data for these patients were collected from the
      German Trauma Registry and from patients' hospital records. Patients who were
      treated in 2010 were compared with patients who were treated in 2011 and 2012,
      following the introduction of the "treatment of patients with severe and multiple
      injuries" guideline in the authors' clinic at the beginning of 2011. RESULTS:
      Significant differences were found in ISS, RTS, New ISS, and TRISS between 2010
      and 2011/2012. No differences were found in the severity of injury when
      classified by different body regions. Major differences were found in the total
      volume replacement, the length of emergency surgery, the length of surgery
      performed within the first 24h and the rate of whole-body computed tomography.
      The mortality rate dropped from 32.48% in 2010 to 18.75% in 2011/2012 (p=0.003).
      CONCLUSIONS: The introduction and use of a guideline-based medical care regime
      for severely injured patients might reduce the rate of mortality.

PMID- 24332466
TI  - Treatment of intertrochanteric fractures in elderly highrisk patients: dynamic
      hip screw vs. external fixation.
AB  - INTRODUCTION: Although the use of a dynamic hip screw (DHS) is considered to be
      the preferred treatment for intertrochanteric fractures, the external fixation
      device could produce clinical outcomes comparable to the outcomes obtained with
      conventional treatment. Furthermore, because external fixation is minimally
      invasive, we expected a lower rate of morbidity. Therefore, we compared the two
      treatments in a clinical trial of elderly patients with intertrochanteric
      fracture. METHODS: 60 elderly high-risk patients with an average age of 78 years
      were treated for intertrochanteric fracture, resulting from a low energy trauma.
      Patients were randomly divided in two groups regarding to treatment. In Group A
      the patients were treated with DHS, while in Group B were treated with external
      fixator. RESULTS: The fixator was well accepted and no patient had significant
      difficulties while sitting or lying. The average intraoperative time was 73 min
      in Group A and 15 min in Group B (p<0.05). 27 patients of Group A need blood
      transfusion postoperatively and none in Group B (p<0.05). The mean duration of
      hospitalization in Group A and Group B was 8.4 and 2.2 days, respectively
      (p<0.05). 9 of patients Group B had pin-track infection grade 2 that all were
      treated by oral antibiotics. There were no differences in comorbidities, quality
      of reduction, screw cut out, bed sore and HHS between the two groups. CONCLUSION:
      Treatment with external fixator is an effective treatment for intertrochanteric
      fractures in elderly highrisk patients. The advantages include quick and simple
      application, minimal blood loss, less radiation exposure, adequate fixation, pain
      reduction, early discharge from hospital, low costs and favourable functional
      outcomes.

PMID- 24332467
TI  - Numeric rating scale: patients' perceptions of its use in postoperative pain
      assessments.
AB  - AIM: The purpose of this study was to describe how patients perceive the use of
      the numeric rating scale in postoperative pain assessments. BACKGROUND: There are
      recommendations to use a pain scale to follow patients' postoperative pain. Most
      patients prefer the NRS but there is a discrepancy between patients and
      healthcare professionals how to interpret the ratings from the pain assessments.
      METHODS: A descriptive design with a phenomenographic approach was used. Semi
      structured interviews were held with 25 patients. RESULTS: Three description
      categories emerged that illustrate patients' perceptions; use of the NRS
      facilitated communication of pain, it put demands on healthcare professionals and
      care routines and it contained interpretation difficulties. CONCLUSION: The NRS
      has a place in pain management according to the patients but there is a need for
      a dialogue to give the patients the opportunity to describe their pain and set a
      common goal.

PMID- 24332468
TI  - Modelling the distribution of a(w), pH and ions in marinated beef meat.
AB  - New beef products from low value cuts could be developed using marinating since
      this process has been shown to improve meat sensorial properties and shelf life.
      However, to optimise the process mathematical models are needed to predict
      evolution of the physicochemical properties that determine biochemical and
      structural changes. Two major works have been carried out to elaborate
      comprehensive models: (1) Thermodynamic models were adapted to predict water
      sorption isotherms and pH of beef meat tissue in presence of salts (NaCl, KCl)
      and organic acids (acetic, lactic, citric and ascorbic acid), (2) Fickian
      numerical models were set up to predict the migration of ions within meat cuts
      using apparent diffusivities previously estimated from 1D experiments. Simulation
      calculations showed reasonable agreement with measurements and can be used to
      investigate the effect of marinating conditions, product heterogeneity, dimension
      and shape. 

PMID- 24332469
TI  - Internet interventions to support lifestyle modification for diabetes management:
      a systematic review of the evidence.
AB  - BACKGROUND: The Internet presents a widely accessible, 24-h means to promote
      chronic disease management. The objective of this review is to identify studies
      that used Internet based interventions to promote lifestyle modification among
      adults with type 2 diabetes. METHODS: We searched PubMed using the terms:
      [internet, computer, phone, smartphone, mhealth, mobile health, web based,
      telehealth, social media, text messages] combined with [diabetes management and
      diabetes control] through January 2013. Studies were included if they described
      an Internet intervention, targeted adults with type 2 diabetes, focused on
      lifestyle modification, and included an evaluation component with behavioral
      outcomes. RESULTS: Of the 2803 papers identified, nine met inclusion criteria.
      Two studies demonstrated improvements in diet and/or physical activity and two
      studies demonstrated improvements in glycemic control comparing web-based
      intervention with control. Successful studies were theory-based, included
      interactive components with tracking and personalized feedback, and provided
      opportunities for peer support. Website utilization declined over time in all
      studies that reported on it. Few studies focused on high risk, underserved
      populations. CONCLUSION: Web-based strategies provide a viable option for
      facilitating diabetes self-management. Future research is needed on the use of
      web-based interventions in underserved communities and studies examining website
      utilization patterns and engagement over time.

PMID- 24332470
TI  - The use of pictograms in the health care: a literature review.
AB  - BACKGROUND: The ability of patients to understand pharmacotherapy information is
      critical to the successful use of medications. One of the risk factors that may
      predispose the patient to non-adherence is the low retention of verbal
      information. Thereby, one way to facilitate the understanding of patients
      regarding prescribed pharmacotherapy is to incorporate pictograms to transmit
      information in a clear, expeditious, and simple manner. OBJECTIVE: To evaluate
      literature on the use of pictograms for health professionals and assess their
      impact on helping patients increase the understanding of and compliance with
      medical instructions. METHODS: Searches were conducted from February to March
      2012. We searched articles in databases, using the keywords: "pictograms,"
      "health," "health care professionals," "medication" and "pictorial
      representation." After this step, we performed a manual sorting, evaluating
      titles and abstracts. The articles were carefully examined according to the
      following variables: (1) geographic location and setting of the studies; (2)
      study design; (3) number of pictograms used; (4) education; (5) sample size; (6)
      age of participants; (7) function of pictograms; (8) limitations described in the
      literature evaluated. RESULTS: The research identified 136 published studies.
      After the exclusion process, 24 studies met inclusion criteria and from those,
      50% were conducted in Africa, and 51.4% were considered effective. In the
      evaluation of the function of the pictograms, to verify their utility, 23 studies
      used to educate patients on the use of medications. The translation and cultural
      adaptation of pictograms was performed in five studies, and one study considered
      this process as validation. CONCLUSION: In this review, the literature contained
      only a few studies employing pictograms by health professionals, and most of
      these were meant for the use of medications. Moreover, the specific results
      reinforce the need for more studies in this area to provide a more complete
      approach about pictograms in the heath care.

PMID- 24332471
TI  - Is the decremental pattern in Lambert-Eaton syndrome different from that in
      myasthenia gravis?
AB  - OBJECTIVE: We reviewed our experience to determine if the decremental pattern
      during low frequency repetitive nerve stimulation (LF-RNS) distinguishes between
      the Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG). METHODS:
      LF-RNS studies were reviewed from 34 LEMS and 44 MG patients, 4 of whom had
      antibodies to muscle specific kinase (MuSK). In each train we calculated the
      ratio between the early and the later decrement. Receiver-operator characteristic
      curves were calculated to determine the ratio that best distinguished between
      LEMS and MG. RESULTS: The late decrement was more often greater in LEMS and the
      converse was true in MG, but with some overlap in values in individual patients.
      A late decrement more than 102% of the early decrement discriminated between LEMS
      and MG in 90% of studies. The decremental pattern in MG patients with MuSK
      antibodies resembled that in LEMS. CONCLUSION: When the decrement becomes
      progressively greater during low frequency RNS, the patient is more likely to
      have LEMS than MG, and in MG, is more likely to have MuSK antibodies.
      SIGNIFICANCE: A progressive decrement in patients otherwise felt to have MG
      should prompt further clinical, serological and electrodiagnostic tests. Further
      studies are needed to assess the decremental pattern in MuSK MG.

PMID- 24332472
TI  - Rapid processing of haptic cues for postural control in blind subjects.
AB  - OBJECTIVES: Vision and touch rapidly lead to postural stabilization in sighted
      subjects. Is touch-induced stabilization more rapid in blind than in sighted
      subjects, owing to cross-modal reorganization of function in the blind? METHODS:
      We estimated the time-period elapsing from onset of availability of haptic
      support to onset of lateral stabilization in a group of early- and late-onset
      blinds. Eleven blind (age 39.4 years+/-11.7SD) and eleven sighted subjects (age
      30.0 years+/-10.0SD), standing eyes closed with feet in tandem position, touched
      a pad with their index finger and withdrew the finger from the pad in sequence.
      EMG of postural muscles and displacement of centre of foot pressure were
      recorded. The task was repeated fifty times, to allow statistical evaluation of
      the latency of EMG and sway changes following the haptic shift. RESULTS: Steady
      state sway (with or without contact with pad, no haptic shift) did not differ
      between blind and sighted. On adding the haptic stimulus, EMG and sway diminished
      in both groups, but at an earlier latency (by about 0.5 s) in the blinds (p
      <0.01). Latencies were still shorter in the early-than late-blinds. When the
      haptic stimulus was withdrawn, both groups increased EMG and sway at equally
      short delays. CONCLUSIONS: Blinds are rapid in implementing adaptive postural
      modifications when granted an external haptic reference. Fast processing of the
      stabilizing haptic spatial-orientation cues may be favoured by cortical
      plasticity in blinds. SIGNIFICANCE: These findings add new information to the
      field of sensory-guided dynamic control of equilibrium in man.

PMID- 24332473
TI  - Attention to food and beverage advertisements as measured by eye-tracking
      technology and the food preferences and choices of youth.
AB  - The purpose of this study was to examine how objective measures of attention to
      food/beverage advertising were associated with the unhealthy food/beverage
      preferences and choices of children and adolescents. A self-report survey and eye
      tracking session were completed by 102 youth (mean age=11.6 years; 56.4% were
      white; 43.1% were female) between April and November 2010. Participants viewed 40
      food/beverage advertisements on a computer and their eye movements were recorded.
      Objective attention measures included total viewing time, fixation length (time
      spent viewing characters/logos, unhealthy food/beverage items), and fixation
      count (number of times an individual stops to examine characters/logos, unhealthy
      food/beverage items). Food/beverage preferences and choices were measured by self
      report. The preferences index summed responses to 12 questions measuring snack
      food and sugar-sweetened beverage preferences and the choices index summed
      responses to eight questions measuring consumption of snack foods and sugar
      sweetened beverages. Regression models examined whether attention to
      food/beverage advertising was associated with food preferences and choices,
      controlling for sex, age, and body mass index z score. The length of time and
      number of times participants looked at unhealthy food and beverage items within
      advertisements were each significantly associated with unhealthy food/beverage
      preferences of youth (P<0.05). Associations were no longer significant after
      controlling for demographic characteristics. Attention to advertising was not
      significantly associated with food/beverage choices. Research with larger samples
      is needed to more fully understand the role of attention. Future research should
      also examine the association between attention to advertising and purchase
      requests, given the important role of parents in the decision-making process
      surrounding food choice. 

PMID- 24332474
TI  - Oxidative stress sensing by the iron-sulfur cluster in the transcription factor,
      SoxR.
AB  - All bacteria are continuously exposed to environmental and/or endogenously active
      oxygen and nitrogen compounds and radicals. To reduce the deleterious effects of
      these reactive species, most bacteria have evolved specific sensor proteins that
      regulate the expression of enzymes that detoxify these species and repair
      proteins. Some bacterial transcriptional regulators containing an iron-sulfur
      cluster are involved in coordinating these physiological responses. Mechanistic
      and structural information can show how these regulators function, in particular,
      how chemical interactions at the cluster drive subsequent regulatory responses.
      The [2Fe-2S] transcription factor SoxR (superoxide response) functions as a
      bacterial sensor of oxidative stress and nitric oxide (NO). This review focuses
      on the mechanisms by which SoxR proteins respond to oxidative stress. 

PMID- 24332475
TI  - Wound complications after distal humerus fracture fixation: incidence, risk
      factors, and outcome.
AB  - BACKGROUND: This study set out to accurately determine the incidence of wound
      complications after distal humerus fracture fixation, to assess risk factors, and
      to determine their implications on outcome. METHODS: Eighty-nine distal humerus
      fractures (mean patient age, 58 years) were treated with internal fixation at an
      average of 4 days after injury. Mean follow-up time was 15 months (range, 6-72
      months). Twenty-nine (33%) fractures were open. Medical records and radiographs
      were reviewed to determine wound complications. Logistic regression analysis was
      carried out to determine associated risk factors. RESULTS: Fourteen patients
      (15.7%) developed a major wound complication requiring on average 2.5 (range, 1
      6) additional surgical procedures. Six patients required plastic surgical soft
      tissue coverage. All 14 fractures complicated by wound problems united. The final
      mean range of motion in the major wound complication group was 100 degrees 
      (range, 65 degrees -130 degrees ), compared with 100 degrees  (range, 10 degrees 
      140 degrees ) in those with no or minor wound problems. Grade III open fractures
      and the use of a plate to stabilize the olecranon osteotomy were identified as
      significant risk factors for development of major wound complications.
      CONCLUSIONS: The incidence of major wound complications after fixation of distal
      humerus fractures is substantial. The presence of a grade III open fracture and
      the use of an olecranon osteotomy stabilized with a plate are significant risk
      factors for major wound complications. Fracture healing rates and functional
      elbow range of motion do not appear to be affected by major wound complications
      when they are handled with proper soft tissue coverage techniques.

PMID- 24332476
TI  - Transient sternoclavicular joint arthropathy, a self-limited disease.
AB  - BACKGROUND: The sternoclavicular joint (SCJ) is a true diarthrodial synovial
      joint and therefore vulnerable to the same disease processes as in other synovial
      joints. We identified a group of patients with monarticular arthritis of the SCJ
      that had a benign process and a self-limited disease course. METHODS: This
      retrospective study included 25 female patients who presented with pain or
      swelling of the SCJ between January 2000 and December 2010. Their mean age was 59
      years, and the average follow-up was 44 months. All patients underwent baseline
      radiographic imaging, technetium bone scan, computed tomography, and magnetic
      resonance imaging. Blood profiles were negative for rheumatoid factor in all
      patients. Functional outcome was assessed with the Rockwood SCJ score. RESULTS:
      The patients presented with complaints of pain (72%), local swelling (88%), and
      redness (8%) that progressed during 4 weeks. The physical examination revealed
      tenderness (84%), swelling (88%), and limited range of motion (16%). These
      findings persisted for a median of 5 months. Plain radiographs showed arthritic
      changes in 5 patients (20%). Increased uptake was observed in all 9 patients who
      underwent a bone scan. Soft tissue swelling was demonstrated on computed
      tomography in 5 patients (20%) and on magnetic resonance imaging in 5 patients
      (20%). One patient had osteoarthritic changes on magnetic resonance imaging. Pain
      resolved spontaneously in all patients, leaving only swelling in 9 patients and
      tenderness in 1 patient. CONCLUSION: Our experience is that SCJ arthropathy may
      often be a self-limited disease. After being treated solely with nonsteroidal
      anti-inflammatory medication, 24 of the 25 study patients showed complete
      regression of pain and return to full function without recurrence of symptoms.
      Basic blood tests and radiographs are sufficient to rule out a septic joint.

PMID- 24332477
TI  - Purification and characterization of a novel fibrinolytic alpha chymotrypsin like
      serine metalloprotease from the edible mushroom, Lyophyllum shimeji.
AB  - A novel fibrinolytic enzyme was purified from Lyophyllum shimeji, a popular
      edible mushroom in Asia. The enzyme was purified using combination of anion
      exchange chromatography on a Mono Q 5/5 column and size exclusion gel filtration
      chromatography on Superdex 200 100/300 column. This purification protocol
      resulted 80.9-fold purification of the enzyme and a final yield of 5.7%. The
      molecular weight of the purified enzyme was estimated to be 21 kDa by SDS-PAGE
      and size exclusion gel filtration. The N-terminal amino acid sequence was found
      to be ITFQSASP, which is dissimilar from that of known fibrinolytic enzymes. The
      purified enzyme was a neutral protease with an optimal reaction pH and
      temperature of 8.0 and 37 degrees C, respectively. Enzymatic activity was
      inhibited by Cu(2+) and Co(2+). It was also significantly inhibited by PMSF and
      TPCK. Furthermore, it was found to exhibit a higher specificity for S-7388, a
      well-known chymotrypsin chromogenic substrate, indicating chymotrypsin like
      serine metalloprotease. The relative fibrinolytic activity of 5 MUg purified
      enzyme have two fold more activity than 1 unit/ml of plasmin on fibrin plate.
      Furthermore, purified enzyme preferentially hydrolyzed the Aalpha-chain followed
      by the Bbeta- and gamma-chain of fibrinogen, which is precursor of fibrin.
      Therefore, these data suggests that the fibrinolytic enzyme derived from edible
      mushroom, L. shimeji, might be useful for thrombolytic therapy and preventing
      thrombotic disease.

PMID- 24332479
TI  - Rectal NSAIDs for the prevention of post-ERCP pancreatitis: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND AND PURPOSE: Acute pancreatitis is the most frequent complication of
      endoscopic retrograde cholangiopancreatography (ERCP). We conducted a meta
      analysis to evaluate the efficacy and safety of rectal nonsteroidal anti
      inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis (PEP).
      METHODS: PubMed and Embase databases were searched through April 2013. Results
      are reported as relative risk (RR) or weighted mean difference (WMD) with 95%
      confidence interval (95% CI). The primary outcome measure was the incidence of
      PEP. Secondary outcome measures included the severity of PEP and serum amylase
      level 2 h, 24 h after ERCP. RESULTS: Seven trials containing 1846 patients were
      eligible. Rectal NSAIDs significantly reduced the incidence of PEP (RR 0.45, 95%
      CI 0.34-0.61, P < 0.001). The results were maintained in subsequent subgroup
      analysis. Rectal NSAIDs also was associated with a reduction in the incidence of
      mild PEP (RR 0.54, 95% CI 0.35-0.83, P = 0.005), moderate to severe PEP (RR 0.39,
      95% CI 0.22-0.70, P = 0.002), or serum amylase level 2 h after ERCP (WMD -91.09
      IU/L, 95% CI -149.78 to -32.40, P = 0.002). CONCLUSIONS: Rectal NSAIDs reduced
      the incidence and severity of PEP, as well as serum amylase level 2 h after ERCP.

PMID- 24332478
TI  - Role of disulfide bond isomerase DsbC, calcium ions, and hemin in cell-free
      protein synthesis of active manganese peroxidase isolated from Phanerochaete
      chrysosporium.
AB  - A cell-free protein synthesis system can produce various types of proteins
      directly from DNA templates such as PCR products, and therefore attracts great
      attention as an alternative protein synthesis system especially for high
      throughput functional screening of proteins. Here, we report successful
      expression of active Phanerochaete chrysosporium manganese peroxidase (MnP) in an
      Escherichia coli cell-free protein synthesis system, wherein reaction conditions
      such as the concentrations of hemin, calcium ions, and disulfide bond isomerase
      were optimized to increase the solubility and activity of the synthesized enzyme.
      Moreover, cell-free synthesized MnP purified using the hemagglutinin tag showed
      higher specific activity than the commercial wild-type enzyme, suggesting that
      the cell-free system can be used as a preparative method for efficient synthesis
      of disulfide bond-containing metalloenzymes such as MnP. We believe that our
      system is a solid foundation for the development of a high-throughput screening
      method for the directed evolution of these enzymes. 

PMID- 24332480
TI  - A committee approach maintaining cultural originality in translation.
AB  - Various methods have been used to translate existing assessment tools and
      clinical nursing materials from one language to another. The method of choice
      depends on the research objectives, availability of translators, budget, and
      time. We highlight our experience using the committee approach to translation.
      This less commonly used approach introduces the concept of cultural consensus
      building early in the translation process, which is particularly appropriate when
      languages are culturally and linguistically distant. Our experience centers on
      the translation of the Primary Communication Inventory (PCI), from English to
      Japanese, to study first-time parents in Japan. 

PMID- 24332481
TI  - BDNF: a biomarker for social vulnerability in individuals diagnosed with gender
      dysphoria.

PMID- 24332483
TI  - Dosimetric evaluation of MapCHECK 2 and 3DVH in the IMRT delivery quality
      assurance process.
AB  - Based on per-field data, 3 dose-volume histogram (DVH) is designed to calculate 3
      dimensional (3D) dose using patient-computed tomography (CT) for an intensity
      modulated radiation therapy (IMRT) delivery quality assurance (DQA) process
      measured with diode detector arrays. In this study, the characteristics and
      suitability of 3DVH for an IMRT DQA process were evaluated by assessment of
      clinically applied results. The DQA plans were prepared with a 2D diode detector
      array (MapCHECK 2) for 20 IMRT patients (10 with head and neck cancer and 10 with
      prostate cancer), and the matching rate between the calculated dose and the
      measured dose was analyzed. The relative dose differences between the original
      IMRT plan and the recalculated plan by 3DVH were evaluated for tumor target and
      organs at risk (OARs). Confidence limits (CLs) were determined for quantification
      of the degree of agreement that should be expected in each DQA method. The
      individual CLs for DQA accuracy of 3D dosimetric evaluation in the tumor target
      and OARs were also calculated to evaluate the differences compared with
      conventional 2D-based DQA results. The matching rates were sufficient to validate
      the accuracy of IMRT DQA analyses and the calculated CL values were reasonable
      values considering the normal criteria of our institution. The 3DVH analysis
      generally had better matching rate than per-field measurement analysis and the CL
      values for OARs were better than those for the planning target volume (PTV). The
      usefulness of the 3DVH tool was verified for IMRT DQA from the point of view of
      dose evaluation in the corresponding patient's CT data. It also enables
      dosimetric evaluation in each important structure (PTV and OARs), which can
      promote more effective evaluation of DQA error in terms of tumor treatment and
      side effects. 

PMID- 24332484
TI  - Fostering a culture of interprofessional education for radiation therapy and
      medical dosimetry students.
AB  - A less-studied aspect of radiation therapy and medical dosimetry education is
      experiential learning through attendance at interprofessional conferences.
      University of North Carolina radiation therapy and medical dosimetry students
      regularly attended morning conferences and daily pretreatment peer review,
      including approximately 145 hours of direct interaction with medical attending
      physicians and residents, medical physicists, and other faculty. We herein
      assessed the effect of their participation in these interprofessional conferences
      on knowledge and communication. The students who graduated from our radiation
      therapy and medical dosimetry programs who were exposed to the interprofessional
      education initiative were compared with those who graduated in the previous
      years. The groups were compared with regard to their knowledge (as assessed by
      grades on end-of-training examinations) and team communication (assessed via
      survey). The results for the 2 groups were compared via exact tests. There was a
      trend for the examination scores for the 2012 cohort to be higher than for the
      2007 to 2011 groups. Survey results suggested that students who attended the
      interprofessional education sessions were more comfortable speaking with
      attending physicians, residents, physicists, and faculty compared with earlier
      students who did not attend these educational sessions. Interprofessional
      education, particularly vertical integration, appears to provide an enhanced
      educational experience both in regard to knowledge (per the examination scores)
      and in building a sense of communication (via the survey results). Integration of
      interprofessional education into radiation therapy and medical dosimetry
      educational programs may represent an opportunity to enrich the learning
      experience in multiple ways and merits further study. 

PMID- 24332482
TI  - Contributions of B cells to lupus pathogenesis.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      production of autoantibodies. This review summarizes first the results obtained
      in the mouse that have revealed how B cell tolerance is breached in SLE. We then
      review the B cell subsets, in addition to the autoAb producing cells, which
      contribute to SLE pathogenesis, focusing on marginal zone B cells, B-1 cells and
      regulatory B cells. Finally, we review the interactions between B cells and other
      immune cells that have been implicated in SLE, such as dendritic cells,
      macrophages, neutrophils and T cells. 

PMID- 24332485
TI  - Field-in-field plan does not improve the dosimetric outcome compared with the
      wedged beams plan for breast cancer radiotherapy.
AB  - To evaluate and compare the dosimetry of field-in-field (FIF) and wedged beams
      (WB) techniques for patients with breast cancer receiving adjuvant radiotherapy
      after conservative surgery. A total of 89 patients with breast cancer
      participated in this study. Each patient received a computed tomography-based
      treatment plan with opposed tangential fields. Two planning techniques (FIF and
      WB) were generated for each patient by using the Pinnacle treatment-planning
      system. Three indices, the homogeneity index (HI), conformity index (CI), and
      uniformity index (UI), as well as maximum dose (Dmax), median dose (D50), number
      of portals, monitor unit (MU), and lung volume at 20Gy (lung20) were used for
      comparison. The mean values tested using a t-test indicated that the WB technique
      had a significantly lower HI (p < 0.0001), a significantly higher CI (p <
      0.0001), and a significantly higher D50 (p = 0.0002) than did the FIF technique.
      The FIF technique had a significantly higher Dmax compared with the WB technique,
      but lung20 did not exhibit a significant difference. By contrast, the FIF
      technique had a significantly higher UI and a significantly lower MU compared
      with the WB technique, but a significantly higher number of portals were found in
      the FIF technique. The FIF technique did not demonstrate superior dosimetric
      results. The WB technique had a significantly lower HI, higher CI, lower Dmax,
      and lower number of portals; but the FIF technique had a significantly higher UI
      and lower MU. 

PMID- 24332486
TI  - Structure activity relationships of fused bicyclic and urea derivatives of
      spirocyclic compounds as potent CCR1 antagonists.
AB  - A series of fused bicyclic and urea derivatives of spirocyclic compounds were
      designed, synthesised and evaluated in vitro as potent CCR1 antagonists. In
      particular, 4 (7nM), 44 (1.3nM), 48 (0.89nM) and 50 (0.63nM) were the most potent
      hCCR1 antagonists in this series of compounds. Moreover, some of these substances
      demonstrated good rodent cross-over, especially 46 which exhibited very high rat
      CCR1 binding affinity with an IC50 value of 16nM. 

PMID- 24332488
TI  - Correlation between chemotype-dependent binding conformations of HSP90alpha/beta
      and isoform selectivity-Implications for the structure-based design of
      HSP90alpha/beta selective inhibitors for treating neurodegenerative diseases.
AB  - HSP90 continues to be a target of interest for neurodegeneration indications.
      Selective knockdown of the HSP90 cytosolic isoforms alpha and beta is sufficient
      to reduce mutant huntingtin protein levels in vitro. Chemotype-dependent binding
      conformations of HSP90alpha/beta appear to strongly influence isoform
      selectivity. The rational design of HSP90alpha/beta inhibitors selective versus
      the mitochondrial (TRAP1) and endoplasmic reticulum (GRP94) isoforms offers a
      potential mitigating strategy for mechanism-based toxicities. Better tolerated
      HSP90 inhibitors would be attractive for targeting chronic neurodegenerative
      diseases such as Huntington's disease. 

PMID- 24332487
TI  - Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK)
      inhibitors.
AB  - The design and synthesis of isoxazole 3 is described, a potent JNK inhibitor with
      two fold selectivity over p38. Optimization of this scaffold led to compounds 27
      and 28 which showed greatly improved selectivity over p38 by maintaining the JNK3
      potency of compound 3. Extensive SAR studies will be described as well as
      preliminary in vivo data of the two lead compounds. 

PMID- 24332489
TI  - Synthesis and evaluation of novel azoles as potent antifungal agents.
AB  - Using a rational approach to the design of antifungal agents, a series of azole
      agents with 1,3,4-oxadiazole side chains were designed and synthesized. The
      results of preliminary in vitro antifungal tests with eight human pathogenic
      compounds showed that all of the title compounds exhibited excellent activities
      against all of the tested fungi except Aspergillus fumigatus. Compounds 11e and
      11f were found to be the most effective, with a minimum inhibitory concentration
      of 0.0039MUg/mL, followed by voriconazole, which has a MIC of 0.0625MUg/mL. The
      1,3,4-oxadiazole side chain is not the major contributor but plays a role in
      eliciting the observed antifungal activity. 

PMID- 24332490
TI  - Novel anthraquinone based chalcone analogues containing an imine fragment:
      synthesis, cytotoxicity and anti-angiogenic activity.
AB  - A new class of imine derivatives of hybrid chalcone analogues containing
      anthraquinone scaffold was synthesized and evaluated for their in vitro cytotoxic
      activity against HeLa, LS174, and A549 cancer cells. The compound 5n with furan
      ring linked to imino group showed potent activity against all target cells with
      IC50 values ranging from 1.76 to 6.11MUM. A mode of action study suggested that
      compounds induced changes typical for apoptosis in HeLa cells. The most active
      compounds inhibited tubulogenesis and 5h was found to exhibit a strong anti
      angiogenic effect. 

PMID- 24332491
TI  - Discovery and optimization of N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4
      c]pyridin-4-yloxy)phenyl)benzenesulfonamides as novel GPR119 agonists.
AB  - The discovery and optimization of novel N-(3-(1,3-dioxo-2,3-dihydro-1H
      pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamide GPR119 agonists is
      described. Modification of the pyridylphthalimide motif of the molecule with
      R(1)=-Me and R(2)=-(i)Pr substituents, incorporated with a 6-fluoro substitution
      on the central phenyl ring offered a potent and metabolically stable tool
      compound 22. 

PMID- 24332492
TI  - Rationally designed hybrid molecules with appreciable COX-2 inhibitory and anti
      nociceptive activities.
AB  - Six molecules were obtained by the combination of three biologically and
      medicinally significant moieties-indole, chrysin and pyrazole. Bio-evaluation of
      these hybrid molecules showed significant inhibition of COX-2 enzymatic activity
      over that of COX-1 and appreciable anti-nociceptive activity, checked at swiss
      albino mice. 

PMID- 24332493
TI  - The discovery of potent, orally bioavailable pyrazolo and triazolopyrimidine
      CXCR2 receptor antagonists.
AB  - A hit-to-lead optimisation programme was carried out on the Novartis archive
      screening hit, pyrazolopyrimidine 2-methyl-5-((phenylthio)methyl)pyrazolo[1,5
      a]pyrimidin-7-ol 1, resulting in the discovery of CXCR2 receptor antagonist 2
      benzyl-5-(((2,3-difluorophenyl)thio)methyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
      14. The SAR was investigated by systematic variation of the pendant thiol, alkyl
      and pyrimidinol groups. Replacement of the pyrazolopyrimidine core with a
      triazolo alternative led to a dual series of antagonists with favourable
      biological and pharmacokinetic properties. 

PMID- 24332494
TI  - Synthesis, biological evaluation and SAR of 3-benzoates of ingenol for treatment
      of actinic keratosis and non-melanoma skin cancer.
AB  - Ingenol 3-benzoates were investigated with respect to chemical stability, pro
      inflammatory effects, cell death induction and PKCdelta activation. A correlation
      between structure, chemical stability and biological activity was found and
      compared to ingenol mebutate (ingenol 3-angelate) used for field treatment of
      actinic keratosis. We also provided further support for involvement of PKCdelta
      for induction of oxidative burst and cytokine release. Molecular modeling and
      dynamics calculations corroborated the essential interactions between key
      compounds and C1 domain of PKCdelta. 

PMID- 24332495
TI  - Synthesis of 3'-O-fluorescently mono-modified reversible terminators and their
      uses in sequencing-by-synthesis.
AB  - Next-generation sequencing (NGS) technologies recently developed are now used for
      study of genomes from various organisms. Sequencing-by-synthesis (SBS) is a key
      strategy in the NGS. The SBS uses nucleotides so-called dual-modified reversible
      terminators (DRTs) in which bases are labeled with fluorophores and 3'-OH is
      protected with a reversibly cleavable chemical group, respectively. In this
      study, we examined the possibility of performing SBS with mono-modified
      reversible terminators (MRTs), in which the reversible blocking group on the 3'
      OH plays a dual role as a fluorescent signal report as well as a chemical
      protection. We studied cyclic reversible termination by using two MRTs (dA and
      dT), wherein the modifications were two different fluorophores and cleavable to
      regenerate a free 3'-OH. We here demonstrated that SBS could be achieved with
      incorporation of MRTs by a DNA polymerase and correct base-calls based on the two
      different colors from the fluorophores. 

PMID- 24332496
TI  - Chemical synthesis and tyrosinase inhibitory activity of rhododendrol glycosides.
AB  - The concise synthesis of rhododendrol glycosides 3-8, which are novel derivatives
      of (+)-epirhododendrin (1) and (-)-rhododendrin (2), has been achieved in six
      steps from benzaldehyde 9. The key reactions include aldol condensation and
      trichloroacetimidate glycosylation. From biological studies, it has been
      determined that synthetic derivatives of 1 and 2 possess potent tyrosinase
      inhibitory activity. Particularly, the inhibitory activity of cellobioside 8
      (IC50=1.51MUM) is six times higher than that of kojic acid. The R-epimers (4, 6,
      and 8) possessed more potent activity than the corresponding S-epimers (3, 5, and
      7), indicating that tyrosinase inhibitory activity is significantly governed by
      stereochemistry of rhododendrol glycosides. 

PMID- 24332497
TI  - Synthesis and anticancer potential of benzothiazole linked
      phenylpyridopyrimidinones and their diones as mitochondrial apoptotic inducers.
AB  - A series of benzothiazole linked phenylpyridopyrimidinones (8a-g) and their
      diones (9a-g) have been designed, synthesized and evaluated for their anticancer
      activity. Among the series one of the conjugate 8b showed significant
      cytotoxicity against human cervical cancer cell line ME-180 with IC50 value of
      4.01MUM. This compound was tested on the cell cycle perturbations and DNA damage.
      Flow cytometry analysis revealed that the compound 8b showed drastic cell cycle
      perturbations due to concentration dependent increase in the sub-G0 phase in ME
      180 cell line. DNA fragmentation and Hoechst staining reveals that this compound
      induced cell death by apoptosis. Further caspase-3 and loss of mitochondrial
      membrane potential suggested that the compound induces cell death by apoptosis. 

PMID- 24332498
TI  - Targeting molecular pathways in endometrial cancer: a focus on the FGFR pathway.
AB  - In the majority of cases, endometrial cancer is localized and highly curable
      through surgery and adjuvant radiotherapy. However, for patients with advanced or
      metastatic disease, prognosis is poor. Systemic treatments such as cytotoxic
      chemotherapy or hormonal therapy can cause significant toxicities including
      chemotherapy-related gastrointestinal, neurologic, and immunosuppressive
      toxicities and hormone-related hypertension, increased blood sugar, thrombosis,
      and pulmonary emboli. In addition, these therapies rarely lead to sustained
      disease control. Novel therapies with greater efficacy and reduced toxicity are
      needed. Recent progress in the identification of genetic abnormalities in cell
      signaling proteins has spurred the development of targeted agents for the
      treatment of patients with endometrial cancer. The fibroblast growth factor
      receptor (FGFR) pathway is one of several signaling pathways that have been
      implicated in the pathogenesis and progression of endometrial cancer. The
      activity of novel FGFR-targeted agents in preclinical endometrial cancer models
      and clinical trials will be reviewed. 

PMID- 24332499
TI  - Conjunctival fat grafting for improved aesthetics of an ocular prosthesis.

PMID- 24332500
TI  - Effects of perforator number and location on the total pedicle flow and perfusion
      of zone IV skin and fat of DIEP flaps.
AB  - BACKGROUND: DIEP flaps are a popular choice for autologous breast reconstruction,
      though many surgeons routinely discard zone IV, limiting transferrable tissue. We
      investigated the effect of altering number and location of perforators supplying
      the flap on total pedicle flow and perfusion of skin and fat of zone IV. METHODS:
      20 cranially-based abdominal epigastric perforator flaps were raised in rats on
      two perforators. The perforators were sequentially clamped and released in a
      randomised order and total pedicle flow measured using microvascular flow-probes,
      on the following perforator combinations: 13 DIEP flaps were raised in post
      mastectomy patients requiring breast reconstruction on two perforators. These
      were clamped and released as before to assess perfusion of fat and skin in zone
      IV using SPY indocyanine-green-fluorescence-angiography scans on the same
      perforator combinations as in our animal study, listed above. RESULTS: All data
      were analysed using 2-way-ANOVA and revealed that vascular flow was significantly
      (p < 0.0001) greater on one perforator as opposed to two. These results were
      supported by our human study, revealing both zone IV fat and skin perfusion were
      significantly (p < 0.0001) greater when a single perforator was used.
      CONCLUSIONS: Our data suggests total pedicle flow and perfusion of zone IV fat
      and skin is significantly higher on a single perforating blood vessel as opposed
      to two. Reasons for these observed differences could be due to changing pressure
      gradients across a piece of tissue prone to venous congestion, with maintenance
      of flow better in a single lumen.

PMID- 24332501
TI  - The 6th International Veterinary Vaccines and Diagnostic Conference (6th IVVDC).

PMID- 24332502
TI  - Vitamin D as an anti-microbial and anti-inflammatory therapy for Cystic Fibrosis.
AB  - Cystic fibrosis (CF) is characterized by chronic infection and inflammation in
      the airways that lead to progressive lung damage and early death. Current anti
      inflammatory therapies are limited by extensive adverse effects or insufficient
      efficacy. There is a large body of studies indicating beneficial anti-microbial
      and anti-inflammatory properties of vitamin D. Since most patients with CF
      present with vitamin D deficiency, and serum vitamin D levels demonstrate a
      positive correlation with lung function and negative correlation with airway
      inflammation and infection, correcting vitamin D deficiency may be an attractive
      therapeutic strategy in CF. The function of vitamin D is intricately tied to its
      metabolism, which may be impaired at multiple steps in patients with CF, with a
      potential to limit the efficacy of vitamin D supplementation. It is likely that
      the aforementioned beneficial properties of vitamin D require supplementation
      with doses of vitamin D markedly higher than those recommended to maintain proper
      bone function. This review will illustrate the potential for supplementation with
      vitamin D or its metabolites to modulate inflammation and improve defence against
      chronic infection in CF lung, as well as appropriate vitamin D supplementation
      strategies for improving lung function in CF. 

PMID- 24332503
TI  - Characteristics of informal caregivers of patients with dementia in Alicante
      province.

PMID- 24332504
TI  - Attitudes of employees of service and trading companies towards people with
      epilepsy and their professional activity in Poland.
AB  - PURPOSE: Attitudes are shaped by the influence of the media and fixed social
      beliefs. Lack of interaction with people suffering from epilepsy may result in an
      inaccurate perception of this particular group. The aim of this study was to
      examine attitudes towards people with epilepsy as potential colleagues. METHOD: A
      group of 187 employees, employed in medium sized service and trading companies
      was analyzed. Each employee completed a questionnaire divided into three attitude
      components: knowledge, emotions and behaviour. Each of these attitude subscales
      was analyzed separately. The results were verified with statistical tests.
      RESULTS: The lowest mean score was obtained by respondents on the knowledge
      subscale, a higher score was obtained on the emotions subscale whilst the highest
      on the behavioural subscale. Over half of respondents expressed an accepting
      attitude towards people with epilepsy. According to 67% of respondents, people
      with epilepsy have equal possibilities as far as access to work is concerned.
      Education had statistically significant scores within the emotions component. No
      correlation was found between any of the declared attitudes of respondents and
      their seniority, age or sex. Familiarity with a person with epilepsy translated
      into a higher level of knowledge and a positive perception of a patient as a
      possible future colleague. CONCLUSIONS: To improve the employment situation of
      people with epilepsy, knowledge among workers should be increased. This should be
      done at various levels of employment to ensure that the risks of employing a
      person with epilepsy are more adequately assessed and mitigated if possible.

PMID- 24332505
TI  - Small renal masses initially managed using active surveillance: results from a
      retrospective study with long-term follow-up.
AB  - BACKGROUND: The purpose of this study was to provide outcomes of patients managed
      using active surveillance (AS) for small renal masses (SRMs). PATIENTS AND
      METHODS: We retrospectively reviewed data of 62 patients diagnosed with 64
      contrast enhancing SRMs suspicious for renal cell carcinoma. We evaluated the
      differences between patients who remained on AS and those who underwent delayed
      surgical intervention. RESULTS: The mean age of patients was 75 years and the
      mean follow-up was 91.5 months. The median tumor size and the median estimated
      tumor volume were 2.6 cm and 8.7 cm(3), respectively. The median linear growth
      rate and the median volumetric growth rate were 0.7 cm/y and 8.8 cm(3)/y,
      respectively. The mean linear and volumetric growth rates of the group of
      patients who underwent surgery was higher than in those who remained on
      surveillance (1.9 vs. 0.4 cm/y and 16.1 vs. 4.6 cm(3)/y, respectively; P < .001).
      CONCLUSION: Most SRMs show an indolent course, with low metastatic potential.
      Faster linear and volumetric growth rates could be the expression of malignant
      disease, thus suggesting the need for a delayed surgical intervention. AS is a
      reasonable option for the management of SRMs in properly selected patients with
      low life expectancy.

PMID- 24332506
TI  - High-dose itraconazole as a noncastrating therapy for a patient with
      biochemically recurrent prostate cancer.

PMID- 24332507
TI  - General adherence to guideline recommendations on initial diagnosis of bladder
      cancer in the United States and influencing factors.
AB  - BACKGROUND: Because international guidelines recommend best practices regarding
      staging of incident bladder cancer, we determined the adherence to such
      recommendations in the United States, performing a large retrospective database
      analysis. PATIENTS AND METHODS: Patients with the diagnosis of urothelial cancer
      were identified in the Surveillance, Epidemiology, and End Results (SEER)
      Medicare database between 1992 and 2007. Staging procedures were identified and
      analyzed. As reference for published recommendations, we used the American
      Urological Association (AUA), European Association of Urology (EAU), and National
      Comprehensive Cancer Network (NCCN) guidelines. Based on these sources,
      recommended initial staging of bladder cancer was analyzed. Of all 56,130
      patients, 6148 (10.9%) had a cytologic examination, 29,677 (52.9%) had a standard
      urinalysis, 2882 (5.1%) underwent intravenous pyelography (IVP), 6950 (12.4%)
      underwent retrograde pyelography (RPG), and 8145 (14.5%) had computed
      tomography/magnetic resonance imaging (CT/MRI). RESULTS: There was a significant
      trend over the years to a higher use of cytologic analysis, standard urinalysis,
      and CT/MRI. We observed a significant trend toward a lower rate of IVP and a
      stable use of RPG. The limitation of our study is that claims data are designed
      for payment processing, not quality measurement. CONCLUSION: Despite published
      recommendations on the initial diagnosis of bladder cancer, our data show that
      less than half of the included patients received all the elements thought to be
      required for an initial diagnosis of bladder cancer as recommended by guidelines.
      Greater adherence to recommendations may ensure optimal treatment strategies.
      Appropriate treatment is critical to patient outcomes, because evidence-based
      therapeutic management can be practiced only if an accurate assessment of the
      disease takes place at the time of initial diagnosis.

PMID- 24332508
TI  - Radical cystectomy in a Dutch University hospital: long-term outcomes and
      prognostic factors in a homogeneous surgery-only series.
AB  - BACKGROUND: The aim of this study was to present survival outcomes and identify
      prognostic factors in patients undergoing radical cystectomy (RC) for urothelial
      bladder cancer (UBC) in a homogeneous surgery-only series. PATIENTS AND METHODS:
      Patients who underwent RC for UBC with intent-to-cure between January 1998 and
      December 2010 without neoadjuvant or adjuvant treatment were included in this
      retrospective study. Clinical and histopathologic data were collected and
      institutional review board approval was obtained. Outcomes of interest were 30
      day mortality (30dM), RFS, and OS. Univariable and multivariable analysis were
      performed. Median follow-up was 9.1 years. RESULTS: Two hundred forty-five
      patients were included with a median age of 65 years (range, 34-92 years). 30dM
      rate was in 5 out of 245 patients (2.0%) and 5-year RFS and OS rates were 67% and
      58%, respectively. A total of 223 patients (91%) underwent lymph node (LN)
      dissection. Median number of removed and positive LNs were 9 and 1.5,
      respectively. Variables independently associated with decreased OS and RFS were
      tumor stage and LN status. In addition, positive soft tissue surgical margin
      (STSM) status was independently associated with decreased OS. In LN-positive
      patients, presence of extranodal extension (ENE) was associated with decreased
      RFS (39.7% vs. 7.3%; P = .005). CONCLUSION: Radical cystectomy for UBC was
      associated with low perioperative mortality rate and provided 5-year disease
      control in approximately two-thirds of patients. Independent prognostic factors
      included tumor stage, LN status (RFS and OS), and STSM status (OS). Presence of
      ENE in LN-positive patients was univariably associated with decreased RFS and OS.

PMID- 24332509
TI  - [Application of the Community Assessment Risk Screen in Primary Care centres of
      the Valencia Health System].
AB  - OBJECTIVE: Application of The Community Assessment Risk Screen (CARS) tool for
      detection of chronic elderly patients at risk of hospital readmission and the
      viability study for its inclusion in health information systems. DESIGN:
      Retrospective cohort study. LOCATION: Health Departments 6, 10, and 11 from the
      Valencia Community. PARTICIPANTS: Patients of 65 and over seen in 6 Primary Care
      centres in December 2008. The sample consisted of 500 patients (sampling error=+/
      4.37%, sampling fraction=1/307). VARIABLES: The CARS tools includes 3items:
      Diagnostics (heart diseases, diabetes, myocardial infarction, stroke, COPD,
      cancer), number of prescribed drugs and hospital admissions or emergency room
      visits in the previous 6months. The data came from SIA-Abucasis, GAIA and MDS,
      and were compared by Primary Care professionals. The end-point was hospital
      admission in 2009. RESULTS: CARS risk levels are related to future readmission
      (P<.001). The value of sensitivity and specificity is 0.64; the tool accurately
      identifies patients with low probability of being hospitalized in the future
      (negative predictive value=0.91, diagnostic efficacy=0.67), but has a positive
      predictive value of 0.24. CONCLUSIONS: CARS does not properly identify the
      population at high risk of hospital readmission. However, if it could be revised
      and the positive predictive value improved, it could be incorporated into the
      Primary Care computer systems and be useful in the initial screening and grouping
      of chronic patients at risk of hospital readmission.

PMID- 24332510
TI  - Radiographic patterns in the diagnostic approach to organizing pneumonia.
AB  - A 56-year-old woman, non-smoker, who complained of dry cough and dyspnea during
      the last month came to the emergency department due to increased dyspnea. The
      chest X-ray showed areas of poorly defined, bilateral alveolar opacities, leading
      to the diagnosis of bronchopneumonia with partial respiratory failure. During
      admission, she experienced an exacerbation of the dyspnea. A high-resolution
      computed tomography scan was performed, showing areas of ground glass opacities
      with interlobular septal thickening ("crazy-paving" pattern), predominantly in
      lower lobes. She required mechanical ventilation and she was admitted to the
      intensive care unit. Subsequently, an open lung biopsy was performed. The
      following questions should be proposed:

PMID- 24332511
TI  - Relationship between buprenorphine adherence and health service utilization and
      costs among opioid dependent patients.
AB  - Buprenorphine-medication assisted therapy (B-MAT) is an effective treatment for
      opioid dependence, but may be considered cost-prohibitive based on ingredient
      cost alone. The purpose of this study was to use medical and pharmacy claims data
      to estimate the healthcare service utilization and costs associated with B-MAT
      adherence among a sample of opioid dependent members. Members were placed into
      two adherence groups based on 1-year medication possession ratio (>= 0.80 vs.
      <0.80). The B-MAT adherent group incurred significantly higher pharmacy charges
      (adjusted means; $6,156 vs. $3,581), but lower outpatient ($9,288 vs. $14,570),
      inpatient ($10,982 vs. $26,470), ER ($1,891 vs. $4,439), and total healthcare
      charges ($28,458 vs. $49,051; p<0.01) compared to non-adherent members. Adherence
      effects were confirmed in general linear models. Though B-MAT adherence requires
      increased pharmacy utilization, adherent individuals were shown to use fewer
      expensive health care services, resulting in overall reduced healthcare
      expenditure compared to non-adherent patients.

PMID- 24332513
TI  - Which bisphosphonate to treat bone metastases?

PMID- 24332512
TI  - Safety and activity of PD1 blockade by pidilizumab in combination with rituximab
      in patients with relapsed follicular lymphoma: a single group, open-label, phase
      2 trial.
AB  - BACKGROUND: Endogenous or iatrogenic antitumour immune responses can improve the
      course of follicular lymphoma, but might be diminished by immune checkpoints in
      the tumour microenvironment. These checkpoints might include effects of
      programmed cell death 1 (PD1), a co-inhibitory receptor that impairs T-cell
      function and is highly expressed on intratumoral T cells. We did this phase 2
      trial to investigate the activity of pidilizumab, a humanised anti-PD1 monoclonal
      antibody, with rituximab in patients with relapsed follicular lymphoma. METHODS:
      We did this open-label, non-randomised trial at the University of Texas MD
      Anderson Cancer Center (Houston, TX, USA). Adult (>=18 years) patients with
      rituximab-sensitive follicular lymphoma relapsing after one to four previous
      therapies were eligible. Pidilizumab was administered at 3 mg/kg intravenously
      every 4 weeks for four infusions, plus eight optional infusions every 4 weeks for
      patients with stable disease or better. Starting 17 days after the first infusion
      of pidilizumab, rituximab was given at 375 mg/m(2) intravenously weekly for 4
      weeks. The primary endpoint was the proportion of patients who achieved an
      objective response (complete response plus partial response according to Revised
      Response Criteria for Malignant Lymphoma). Analysis was by intention to treat.
      This trial is registered with ClinicalTrials.gov, number NCT00904722. FINDINGS:
      We enrolled 32 patients between Jan 13, 2010, and Jan 20, 2012. Median follow-up
      was 15.4 months (IQR 10.1-21.0). The combination of pidilizumab and rituximab was
      well tolerated, with no autoimmune or treatment-related adverse events of grade 3
      or 4. The most common adverse events of grade 1 were anaemia (14 patients) and
      fatigue (13 patients), and the most common adverse event of grade 2 was
      respiratory infection (five patients). Of the 29 patients evaluable for activity,
      19 (66%) achieved an objective response: complete responses were noted in 15
      (52%) patients and partial responses in four (14%). INTERPRETATION: The
      combination of pidilizumab plus rituximab is well tolerated and active in
      patients with relapsed follicular lymphoma. Our results suggest that immune
      checkpoint blockade is worthy of further study in follicular lymphoma. FUNDING:
      National Institutes of Health, Leukemia and Lymphoma Society, Cure Tech, and
      University of Texas MD Anderson Cancer Center.

PMID- 24332514
TI  - Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone
      metastases from breast cancer: a randomised, open label, non-inferiority phase 3
      trial.
AB  - BACKGROUND: Bisphosphonates are routinely used in the treatment of metastatic
      bone disease from breast cancer to reduce pain and bone destruction. Zoledronic
      acid given by intravenous infusion has been widely used, but places a substantial
      logistical burden on both patient and hospital. As a result, the use of oral
      ibandronic acid has increased, despite the absence of comparative data. In the
      ZICE trial, we compared oral ibandronic acid with intravenous zoledronic acid for
      the treatment of metastatic breast cancer to bone. METHODS: This phase 3, open
      label, parallel group active-controlled, multicentre, randomised, non-inferiority
      phase 3 study was done in 99 UK hospitals. Eligibility criteria included at least
      one radiologically confirmed bone metastasis from a histologically confirmed
      breast cancer. Patients with ECOG performance status 0 to 2 and clinical decision
      to treat with bisphosphonates within 3 months of randomisation were randomly
      assigned to receive 96 weeks of treatment with either intravenous zoledronic acid
      at 4 mg every 3-4 weeks or oral ibandronic acid 50 mg daily. Randomisation (1:1)
      was done via a central computerised system within stratified block sizes of four.
      Randomisation was stratified on whether patients had current or planned treatment
      with chemotherapy; current or planned treatment with hormone therapy; and whether
      they had a previous skeletal-related event within the last 3 months or had
      planned radiotherapy treatment to the bone or planned orthopaedic surgery due to
      bone metastases. The primary non-inferiority endpoint was the frequency and
      timing of skeletal-related events over 96 weeks, analysed using a per-protocol
      analysis. All active (non-withdrawn) patients have now reached the 96-week
      timepoint and the trial is now in long-term follow-up. The trial is registered
      with ClinicalTrials.gov, number NCT00326820. FINDINGS: Between Jan 13, 2006, and
      Oct 4, 2010, 705 patients were randomly assigned to receive ibandronic acid and
      699 to receive zoledronic acid; three patients withdrew immediately after
      randomisation. The per-protocol analysis included 654 patients in the ibandronic
      acid group and 672 in the zoledronic acid group. Annual rates of skeletal-related
      events were 0.499 (95% CI 0.454-0.549) with ibandronic acid and 0.435 (0.393
      0.480) with zoledronic acid; the rate ratio for skeletal-related events was 1.148
      (95% CI 0.967-1.362). The upper CI was greater than the margin of non-inferiority
      of 1.08; therefore, we could not reject the null hypothesis that ibandronic acid
      was inferior to zoledronic acid. More patients in the zoledronic acid group had
      renal toxic effects than in the ibandronic acid group (226 [32%] of 697 vs 172
      [24%] of 704) but rates of osteonecrosis of the jaw were low in both groups (nine
      [1%] of 697 vs five [<1%] of 704). The most common grade 3 or 4 adverse events
      were fatigue (97 [14%] of 697 patients allocated zoledronic acid vs 98 [14%] of
      704 allocated ibandronic acid), increased bone pain (91 [corrected] [13%] vs 85
      [corrected] [12%]), joint pain (41 [corrected] [6%] vs 38 [5%]), infection (31
      [5%] vs 23 [corrected] [3%]), and nausea or vomiting (38 [5%] vs 41 [6%]).
      INTERPRETATION: Our results suggest that zoledronic acid is preferable to
      ibandronic acid in preventing skeletal-related events caused by bone metastases.
      However, both drugs have acceptable side-effect profiles and the oral formulation
      is more convenient, and could still be considered if the patient has a strong
      preference or if difficulties occur with intravenous infusions. FUNDING: Roche
      Products Ltd (educational grant), supported by National Institute for Health
      Research Cancer Network, following endorsement by Cancer Research UK
      (CRUKE/04/022).

PMID- 24332515
TI  - Evidence-based treatment for low-risk basal cell carcinoma.

PMID- 24332517
TI  - Anti-PD1 antibody: a new approach to treatment of lymphomas.

PMID- 24332516
TI  - Surgical excision versus imiquimod 5% cream for nodular and superficial basal
      cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled
      trial.
AB  - BACKGROUND: Basal-cell carcinoma is the most common form of skin cancer and its
      incidence is increasing worldwide. We aimed to assess the effectiveness of
      imiquimod cream versus surgical excision in patients with low-risk basal-cell
      carcinoma. METHODS: We did a multicentre, parallel-group, pragmatic, non
      inferiority, randomised controlled trial at 12 centres in the UK, in which
      patients were recruited between June 19, 2003, and Feb 22, 2007, with 3 year
      follow-up from June 26, 2006, to May 26, 2010. Participants of any age were
      eligible if they had histologically confirmed primary nodular or superficial
      basal-cell carcinoma at low-risk sites. We excluded patients with morphoeic or
      recurrent basal-cell carcinoma and those with Gorlin syndrome. Participants were
      randomly assigned (1:1) via computer-generated blocked randomisation, stratified
      by centre and tumour type, to receive either imiquimod 5% cream once daily for 6
      weeks (superficial) or 12 weeks (nodular), or surgical excision with a 4 mm
      margin. The randomisation sequence was concealed from study investigators.
      Because of the nature of the interventions, masking of participants was not
      possible and masking of outcome assessors was only partly possible. The trial
      statistician was masked to allocation until all analyses had been done. The
      primary outcome was the proportion of participants with clinical success, defined
      as absence of initial treatment failure or signs of recurrence at 3 years from
      start of treatment. We used a prespecified non-inferiority margin of a relative
      risk (RR) of 0.87. Analysis was by a modified intention-to-treat population and
      per protocol. This study is registered as an International Standard Randomised
      Controlled Trial (ISRCTN48755084), and with ClinicalTrials.gov, number
      NCT00066872. FINDINGS: 501 participants were randomly assigned to the imiquimod
      group (n=254) or the surgical excision group (n=247). At year 3, 401 (80%)
      patients were included in the modified intention-to-treat group. At 3 years, 178
      (84%) of 213 participants in the imiquimod group were treated successfully
      compared with 185 (98%) of 188 participants in the surgery group (RR 0.84, 98% CI
      0.78-0.91; p<0.0001). No clear difference was noted between groups in patient
      assessed cosmetic outcomes. The most common adverse events were itching (211
      patients in the imiquimod group vs 129 in the surgery group) and weeping (160 vs
      81). We recorded serious adverse events in 99 (40%) of 249 participants in the
      imiquimod group and 97 (42%) of 229 in the surgery group had serious adverse
      events, but none were regarded as related to treatment. 12 (5%) participants in
      the imiquimod group withdrew because of adverse events compared with four (2%) in
      the surgery group. INTERPRETATION: Imiquimod was inferior to surgery according to
      our predefined non-inferiority criterion. Although excisional surgery remains the
      best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be
      a useful treatment option for small low-risk superficial or nodular basal-cell
      carcinoma dependent on factors such as patient preference, size and site of the
      lesion, and whether the patient has more than one lesion. FUNDING: Cancer
      Research UK.

PMID- 24332518
TI  - Impact of a third stage of labor oxytocin protocol on cesarean delivery outcomes.
AB  - BACKGROUND: There are currently no standard recommendations regarding the dose,
      rate, or duration of intravenous oxytocin administration for the active
      management of the third stage of labor in the USA. In 2008, we initiated a
      standardized postpartum oxytocin protocol for active management of the third
      stage of labor. In cesarean deliveries, upon clamping of the umbilical cord, an
      oxytocin infusion of 18 U/h was started and adjusted upward if there was ongoing
      uterine atony. The aim of this study was to compare intraoperative data on
      oxytocin dose, estimated blood loss, supplemental uterotonic use and vasopressor
      use before and after the implementation of this protocol. We hypothesized that
      implementation of the protocol would result in lower intraoperative oxytocin
      doses without increasing estimated blood loss. METHODS: In this retrospective
      study, patient characteristics, estimated blood loss, vasopressor administration,
      and supplemental uterotonic use during two time periods were compared: the two
      month interval before initiation of the oxytocin protocol and the two-month
      interval after initiation. Data were compared using the chi-squared test, t-test,
      or Mann-Whitney U test as appropriate. P < 0.05 was considered significant.
      RESULTS: Data for 901 deliveries were analyzed. The amount of intraoperative
      oxytocin administered decreased after implementation of the protocol (median
      difference 8.4 U, 95% CI 7.4 to 9.4). Although there was an increase in estimated
      blood loss, there were no differences in the percentage of patients experiencing
      intraoperative blood loss >1000 mL or the need for additional uterotonic
      mediations between the two time periods. CONCLUSIONS: We found that the use of an
      oxytocin management protocol reduced the amount of intraoperative oxytocin
      administered without increasing the rate of postpartum hemorrhage or the need for
      additional uterotonics. Clinicians may consider using a rate of 18 U/h as a
      starting point for administration of oxytocin to achieve adequate uterine tone in
      healthy parturients for prevention of postpartum hemorrhage.

PMID- 24332519
TI  - Use of telemedicine for providing medical abortion.

PMID- 24332520
TI  - Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the
      jaws: a retrospective analysis from the Copenhagen cohort and a proposal for an
      updated classification system.
AB  - OBJECTIVE: Nonexposed osteonecrosis of the jaws (NE-ONJ) does not fit into the
      current definition of osteonecrosis, which requires exposed bone. A modification
      of the classification of bisphosphonate-induced osteonecrosis of the jaws (ONJ)
      is proposed. This study aimed to test proposed criteria for NE-ONJ and compare NE
      ONJ with exposed ONJ (E-ONJ) in a retrospective analysis. STUDY DESIGN: In 102
      patients with E-ONJ diagnosed according to Ruggiero et al. (2006, 2009), criteria
      for NE-ONJ were developed. Subgroups of NE-ONJ and E-ONJ were tested against each
      other using nonparametric and parametric statistics. RESULTS: Among 102 patients
      with ONJ, 14 had NE-ONJ and 88 had E-ONJ. NE-ONJ and E-ONJ were similar in all
      important data (P > .05) except bone exposure. CONCLUSIONS: NE-ONJ belongs to the
      same disease condition as E-ONJ. NE-ONJ may be otherwise classified as ONJ stage
      1, 2, or 3 and is different from ONJ stage 0. We propose to include the criteria
      for NE-ONJ into the classification.

PMID- 24332521
TI  - Blue-violet light-emitting diode irradiation in combination with hemostatic
      gelatin sponge (Spongel) application ameliorates immediate socket bleeding in
      patients taking warfarin.
AB  - OBJECTIVE: The control of bleeding after tooth extraction is a major concern in
      patients taking warfarin. Light-emitting diode (LED) irradiation with hemostatic
      gelatin sponge application was investigated. STUDY DESIGN: Patients who took
      warfarin and required tooth extraction were divided randomly into 3 groups. The
      first group was irradiated with blue-violet LED after tooth extraction. The
      second group was treated with a hemostatic gelatin sponge and LED irradiation.
      The third group was treated with only hemostatic gelatin sponges. Hemostasis was
      evaluated at 30 seconds after treatment. RESULTS: Less than 30% of the patients
      achieved hemostasis within 30 seconds in the hemostatic sponge group;
      approximately 50% of the patients in the simple LED irradiation group achieved
      hemostasis within 30 seconds; and 86.7% of the patients in the LED and hemostatic
      sponge combined group achieved hemostasis within 30 seconds, indicating that
      combined treatment with LED and hemostatic sponges provided a significantly
      higher hemostasis than in the hemostatic sponge group (P < .01). CONCLUSIONS:
      Blue-violet LED irradiation combined with hemostatic gelatin sponge treatment
      yielded hemostasis of the extraction socket within 30 seconds without suture in
      most cases.

PMID- 24332522
TI  - The detection and role of lymphatic and blood vessel invasion in predicting
      survival in patients with node negative operable primary colorectal cancer.
AB  - Although vascular invasion in colorectal cancer has been recognised since 1938,
      detection methods and results remain inconsistent. Vascular invasion is currently
      an independent prognostic factor in colorectal cancer influencing disease
      progression and survival. The vascular system consists of three components,
      arterial, venous and lymphatic vessels, all of which can be invaded but accurate
      distinction between the components remains difficult with routine staining
      techniques. Even though higher detection rates with elastica staining, for large
      vessel invasion, and recent techniques for immunohistochemistry for small vessel
      invasion, have been reported, a standardised method of detection has not been
      agreed upon which is reflected in the variability of published results. As a
      result of the Bowel Cancer Screening Programme in the UK it will be necessary to
      attempt to identify and stratify patients better, to be able to handle the stage
      migration to early node negative colorectal cancer. At present up to a third of
      patients, with node-negative colorectal cancer on conventional histopathological
      analysis, ultimately die of recurrent disease. It is therefore important to
      develop and standardised methods to identify lymphatic and blood vessel invasion
      which will influence ultimate survival. The present review summarises the current
      status of detection methods for these components of vascular invasion. 

PMID- 24332523
TI  - Trend in the prevalence of obesity and overweight among Iranian children and
      adolescents: a systematic review and meta-analysis.
AB  - OBJECTIVE: Childhood obesity is an important predisposing factor for most non
      communicable diseases. The aim of this review was to provide evidence on the
      prevalence and trends of childhood obesity and overweight in Iran. METHODS:
      Multiple international and Iranian scientific databases were searched for
      relevant literatures. Two independent reviewers identified relevant papers in
      several steps. Separate meta-analyses (using fixed- or random-effect models) were
      performed to estimate the overall, age, sex, and age-sex specific prevalence of
      obesity and overweight. Stratified analysis based on Centers for Disease Control
      and Prevention, International Obesity Task Force, and World Health Organization
      definition criteria and study year also were performed. RESULTS: We included 107
      studies in the meta-analysis (49 English and 58 Persian). Based on Centers for
      Disease Control and Prevention definition criteria, the overall prevalence of
      obesity and overweight remained relatively constant in the 2000s and are
      estimated to be about 5.1% (95% confidence interval [CI], 4.4-5.8) and 10.8% (95%
      CI, 10.2-11.4), respectively. The meta-regression analysis showed that the
      prevalence of obesity and overweight did not vary significantly with respect to
      sex and age of study participants. Girls had a lower prevalence of obesity and
      higher prevalence of overweight than boys. CONCLUSION: This review, which is the
      first of its kind in the Middle East and North Africa, suggests that although the
      trend in the prevalence of childhood obesity in Iranian children is not
      considerably high, but the escalating trend of excess weight among young children
      is alarming and should be considered by providers of interventional preventive
      programs at national and regional levels.

PMID- 24332524
TI  - Oligofructose-enriched inulin improves some inflammatory markers and metabolic
      endotoxemia in women with type 2 diabetes mellitus: a randomized controlled
      clinical trial.
AB  - OBJECTIVES: Anti-inflammatory therapeutic approaches are considered for the
      management of type 2 diabetes and for the prevention of its complications. There
      is limited evidence regarding the effects of prebiotics on inflammation,
      especially in patients with type 2 diabetes. This trial aims to examine the
      effects of oligofructose-enriched inulin on glycemic status, inflammation
      markers, and metabolic endotoxemia in female patients. METHODS: Over a period of
      8 wk, 52 women with body mass indices of >25 kg/m(2) but <35 kg/m(2) with type 2
      diabetes were randomly assigned to either an intervention group, in which
      participants were given oligofructose-enriched inulin (n = 27, consuming 10 g/d
      of oligofructose-enriched inulin), or to a control group, in which participants
      were given maltodextrin (n = 25, consuming 10 g/d of maltodextrin). Fasting
      plasma glucose, glycosylated hemoglobin, high-sensitivity C-reactive protein,
      interleukin-6, tumor necrosis factor-alpha, interferon-gamma, interleukin-10, and
      plasma lipopolysaccharide were measured before and after the intervention. Data
      were analyzed with the use of SPSS software version 13. Paired and unpaired
      Student t tests and analysis of covariance were used to compare quantitative
      variables. RESULTS: Oligofructose-enriched inulin caused a significant decrease
      in the levels of fasting plasma glucose (19.2 mg/dL; 9.50%), glycosylated
      hemoglobin (1.0%; 8.40%), interleukin-6 (1.3 pg/mL; 8.15%), tumor necrosis factor
      alpha (3.0 pg/mL; 19.80%) and plasma lipopolysaccharide (6.0 EU/mL; 21.95%) as
      compared with maltodextrin (P < 0.05). Decreases in levels of interferon-gamma
      (0.3 pg/mL; 16.50%) and high-sensitivity C-reactive protein (3.9 ng/mL; 31.70%)
      and an increase in the level of interleukin-10 (0.4 pg/mL, 11.50%) were not
      significant in the oligofructose-enriched inulin group as compared with the
      maltodextrin group. CONCLUSIONS: In women with type 2 diabetes and suboptimal
      daily dietary fiber intake, oligofructose-enriched inulin may help to modulate
      some inflammatory markers.

PMID- 24332525
TI  - Anemia in severe acute malnutrition.
AB  - OBJECTIVES: India has the highest prevalence of severe acute malnutrition (SAM).
      Severe anemia is one of the comorbidities responsible for increased mortality in
      severely malnourished children, yet it has not received the attention it should.
      The aim of the present study was to determine the prevalence and type of anemia
      and to evaluate the possible etiologies for severe anemia, in these children.
      METHODS: A cross-sectional study of patients with SAM in a tertiary care hospital
      in northern India over a period of 12 mo from Sept. 1, 2010 to Aug. 31, 2011 was
      conducted. We observed the prevalence of severe anemia (hemoglobin < 7 g/dL),
      morphologic type of anemia, number of patients requiring blood transfusion,
      hematologic profile of mothers, nature of feeding, duration of exclusive
      breastfeeding, and the demographic profile of these patients. RESULTS: Included
      in the study were 131 cases of SAM. The age group varied between 6 and to 59 mo.
      Of patients with SAM, 67.3% had severe anemia; 13.8% had moderate anemia. Of
      these patients, 25% required packed red blood cell transfusion. The most common
      type of anemia was microcytic (38.6%) followed by megaloblastic (30.5%).
      CONCLUSIONS: A high incidence of severe anemia in SAM with a large proportion
      (25%) requiring blood transfusion is a pointer toward nutritional anemia being a
      very common comorbidity of SAM requiring hospital admission. Because
      megaloblastic anemia closely followed microcytic anemia, supplementation with
      vitamin B12 in addition to iron and folic acid would be recommended.

PMID- 24332526
TI  - Waist-to-height ratio: an accurate anthropometric index of abdominal adiposity
      and a predictor of high HOMA-IR values in nondialyzed chronic kidney disease
      patients.
AB  - OBJECTIVE: Chronic kidney disease (CKD) is associated with metabolic disorders,
      including insulin resistance (IR), mainly when associated with obesity and
      characterized by high abdominal adiposity (AbAd). Anthropometric measures are
      recommended for assessing AbAd in clinical settings, but their accuracies need to
      be evaluated. The aim of this study was to evaluate the precision of different
      anthropometric measures of AbAd in patients with CKD. We also sought to determine
      the AbAd association with high homeostasis model assessment index of insulin
      resistance (HOMA-IR) values and the cutoff point for AbAd index to predict high
      HOMA-IR values. METHODS: A subset of clinically stable nondialyzed patients with
      CKD followed at a multidisciplinary outpatient clinic was enrolled in this cross
      sectional study. The accuracy of the following anthropometric indices: waist
      circumference, waist-to-hip ratio, conicity index and waist-to-height ratio
      (WheiR) to assess AbAd, was evaluated using trunk fat, by dual x-ray
      absorptiometry (DXA), as a reference method. HOMA-IR was estimated to stratify
      patients in high and low HOMA-IR groups. The total area under the receiver
      operating characteristic curves (AUC-ROC; sensitivity/specificity) was
      calculated: AbAd with high HOMA-IR values (95% confidence interval [CI]).
      RESULTS: We studied 134 patients (55% males; 54% overweight/obese, body mass
      index >= 25 kg/m(2), age 64.9 +/- 12.5 y, estimated glomerular filtration rate
      29.0 +/- 12.7 mL/min). Among studied AbAd indices, WheiR was the only one to show
      correlation with DXA trunk fat after adjusting for confounders (P < 0.0001).
      Thus, WheiR was used to evaluate the association between AbAd with HOMA-IR values
      (r = 0.47; P < 0.0001). The cutoff point for WheiR as a predictor for high HOMA
      IR values was 0.55 (AUC-ROC = 0.69 +/- 0.05; 95% CI, 0.60-0.77;
      sensitivity/specificity, 68.9/61.9). CONCLUSIONS: WheiR is recommended as an
      effective and precise anthropometric index to assess AbAd and to predict high
      HOMA-IR values in nondialyzed patients with CKD.

PMID- 24332527
TI  - Myofibrillar protein overdegradation in overweight patients with chronic heart
      failure: the relationship to serum potassium levels.
AB  - OBJECTIVES: Muscle release of the amino acid 3-methyl-histidine (3MH) is a
      sensitive index of myofibrillar protein overdegradation (MPO). We hypothesized
      that patients with chronic heart failure (CHF) could have increased muscle
      release of 3MH, which in turn reflects MPO, and that serum electrolyte sodium
      (Na(+)) and potassium (K(+)) levels may be associated with this 3MH muscle
      release. METHODS: Thirty-one overweight outpatients (body mass index, 27 +/- 4.4
      kg/m(2); 22 men and 9 women; age, 56 +/- 8.7 y) with clinically stable CHF were
      studied. After a 24-hour meat-free diet and overnight fasting, patients underwent
      blood sampling from a cannulated arm vein (V) and concomitantly from the arterial
      artery (A) to determine plasma 3MH levels and to calculate the A-V difference.
      Serum levels of Na(+) and K(+) in the venous blood were determined, and the
      Na(+)/K(+) ratio was calculated. Ten healthy subjects who were matched for
      gender, age, and body mass index served as controls and underwent the same
      protocol as the patients with CHF. RESULTS: The patient group had higher arterial
      (P = 0.02) and venous (P = 0.005) 3MH levels but a similar A-V 3MH difference (P
      = 0.28) as compared with the controls. Within the CHF group, 67.7% of patients
      released 3MH, which resulted in a negative A-V value (P < 0.02 as compared with
      controls). In patients with CHF, the A-V 3MH difference correlated positively
      with the serum K(+) level (r = 0.62; P = 0.0002) and negatively with Na(+)/K(+)
      ratio (r = -0.55; P = 0.002). No association was found between the A-V 3MH
      difference and the Na(+) level. CONCLUSIONS: The study demonstrated the existence
      of MPO in resting overweight patients with CHF, thereby suggesting that low serum
      levels of K(+) may contribute to MPO.

PMID- 24332528
TI  - Multicenter study on costs associated with two surgical procedures: GreenLight
      XPS 180 W versus the gold standard transurethral resection of the prostate.
AB  - OBJECTIVE: To analyze the costs associated with two surgical procedures for lower
      urinary tract symptoms secondary to benign prostatic hyperplasia: GreenLight XPS
      180|W versus the gold standard transurethral resection of the prostate. METHODS:
      A multicenter, retrospective cost study was carried out from the National Health
      Service perspective, over a 3-month time period. Costs were broken down into pre
      surgical, surgical and post-surgical phases. Data were extracted from records of
      patients operated sequentially, with IPSS=15, Qmax=15 mL/seg and a prostate
      volume of 40-80mL, adding only direct healthcare costs (?, 2013) associated with
      the procedure and management of complications. RESULTS: A total of 79 patients
      sequentially underwent GL XPS (n: 39) or TURP (n: 40) between July and October,
      2013. Clinical outcomes were similar (94.9% and 92.5%, GL XPS and TURP,
      respectively) without significant differences (P=.67). The average direct cost
      per patient was reduced by ?114 in GL XPS versus TURP patients; the cost was
      higher in the surgical phase with GL XPS (difference: ?1,209; P<.001) but was
      lower in the post-surgical phase (difference: ?-1,351; P<.001). CONCLUSIONS: The
      GreenLight XPS 180-W laser system is associated with a reduction in costs with
      respect to transurethral resection of prostate in the surgical treatment of LUTS
      secondary to PBH. This reduction is due to a shorter inpatient length of stay
      that offsets the cost of the new technology.

PMID- 24332529
TI  - Simulators help improve student confidence to acquire skills in urology.
AB  - OBJECTIVE: To know the level of confidence of fifth year medical students in
      order to perform maneuvers in bladder catheterization and rectal examination
      before and after training with simulators. To be able to assess student
      satisfaction regarding the use of the simulation as a learning method. MATERIAL
      AND METHODS: The study was conducted in the Simulation Center of the Faculty of
      Medicine. A total of 173 students who completed a practical workshop on the
      subject of Urology participated. The students were asked to answer anonymous
      questionnaires on their level of confidence in performing a bladder
      catheterization and rectal examination before and after the workshop as well as
      their satisfaction in using the simulation as a training tool. The workshops were
      organized using groups of 10 students. A teacher or a resident in that area of
      expertise supervised each student individually, resolving their doubts and
      teaching them the proper technique. RESULTS: All the evaluations made on the
      different abilities were significantly higher after training (P<.001).
      Significant differences were found in the confidence level between men and women
      before the training regarding male urethral catheterization maneuvers and
      recognition of normal or pathological prostate, The confidence level was lower in
      women (P<.05). These differences disappeared after training. The level of overall
      satisfaction with the workshop was high, going from 4.47 +/- 0.9 to a maximum
      score of 5. CONCLUSIONS: Simulation is a training method that helps improve the
      confidence of the medical student in performing a bladder catheterization and
      digital rectal examination.

PMID- 24332530
TI  - Preference for erectile dysfunction treatments: Assessment by means of consumers
      preference analysis techniques.
AB  - INTRODUCTION: Patient preference for erectile dysfunction (ED) treatments is of
      great importance for satisfaction and adherence. We have assessed the usefulness
      of the main technique for assessing consumer preferences (conjoint analysis) to
      analyze preferences towards these treatments. We also assessed the influence of
      age, frequency of sexual intercourse, co-morbidities, ED severity or having
      testosterone deficiency syndrome (TDS). MATERIAL AND METHOD: Observational, cross
      sectional, multicenter study in 626 men aged >=18 years that had recently taken
      at least two different PDE5i, one being vardenafil orodispersible (ODT). Seven
      selected features of ED treatments were tested. Different series of scenarios
      (cards) were created by combining these features: two series of 4 features (9
      cards), another one series of 7 (16 cards). Short series were tested in Primary
      Care, and the long series in Urology/Andrology offices. Influences were tested by
      rank ordered logistic regression analysis. RESULTS: The feature "administration
      form" was consistently given the most relative importance; the ODT form was given
      the greatest utility. Consensus towards the most and least preferred treatment
      was achieved only in one of the short series tested. Only severity of TDS
      symptoms, or having the most frequent symptoms, influenced treatment preference.
      Influence was mild. CONCLUSIONS: Conjoint analysis is a valid method for
      assessing preferences for ED treatments. A short series of highly selected
      attributes is advisable. Easiness and convenience of administration are of great
      importance for users. TDS symptomatology mildly affects preference.

PMID- 24332531
TI  - Transmission of "split anergy" from tumor infiltrating to peripheral NK cells in
      a manner similar to "infectious tolerance".
AB  - According to a new paradigm of carcinogenesis, a tumor arises not from
      transformed cell, but only from tumor initiating cells called cancer stem cells
      (CSCs), which can originate from tissue stem cells. CSC are resistant to
      conventional therapy and after treatment form new tumors and give rise to
      metastases. Only natural killer (NK) cells are capable of lysing CSCs, but within
      different tumor types these cells experience a condition known as "split anergy",
      whereby the NK cells lose the ability to kill CSCs and being to produce
      cytokines. As a result, uncontrolled tumor growth arises and tumor stroma
      accumulates anergic NK cells. We hypothesize that anergic tumor infiltrating NK
      (TINK) cells transmit their property to naive NK cells by infecting" them with a
      state of "split anergy" in a similar manner as T conventional cells are
      transformed into T regulatory cells during the process of "infectious tolerance".
      Anergic TINK cells egress from the tumor stroma via the lymphatic system, where
      they reach regional lymph nodes and transmit their properties to naive NK cells,
      which in turn become anergic toward CSCs and lose immunosurveillance functions.
      The mechanisms proposed for this hypothesis and the methodological approaches for
      confirming the idea are presented in this issue. 

PMID- 24332532
TI  - Facilitative effects of bi-hemispheric tDCS in cognitive deficits of Parkinson
      disease patients.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily
      characterized by motor symptoms such as tremor, rigidity, bradykinesia,
      stiffness, slowness and impaired equilibrium. Although the motor symptoms have
      been the focus in PD, slight cognitive deficits are commonly found in non
      demented and non-depressed PD patients, even in early stages of the disease,
      which have been linked to the subsequent development of pathological dementia.
      Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep
      brain stimulation (DBS) have yield controversial results concerning the cognitive
      symptoms amelioration in PD patients. That does not seems to be the case with
      transcranial direct current stimulation (tDCS), although better stimulation
      parameters are needed. Therefore we hypothesize that simultaneously delivering
      cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal
      tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD
      patients, either by mechanisms of homeostatic plasticity and by increases in the
      extracellular dopamine levels over the striatum. 

PMID- 24332533
TI  - Pro-inflammatory cytokines mediate the decrease in serum 25(OH)D concentrations
      after total knee arthroplasty?
AB  - Vitamin D is a fat-soluble micronutrient that regulates inflammation and skeletal
      muscle size and function. Inflammation and skeletal muscle dysfunction (i.e.,
      atrophy and weakness) are predominant impairments that continue to challenge the
      rehabilitation from total knee arthroplasty (TKA). Data suggest a decrease in
      serum 25-hydroxyvitamin D (25(OH)D) concentrations after TKA. Despite the
      decrease being attributed to a systemic inflammatory response, it is unclear what
      inflammatory mediator(s) is contributing to the decrease in serum 25(OH)D
      concentrations after TKA. In immune cells, pro-inflammatory cytokines mediate the
      enzymatic conversion of 25(OH)D to 1,25-dihydroxyvitamin D, implying that pro
      inflammatory cytokines contribute to the decrease in substrate availability
      (i.e., 25(OH)D). We propose the hypothesis that pro-inflammatory cytokines
      mediate the decrease in serum 25(OH)D concentrations after TKA. To complement the
      supporting literature for the proposed hypothesis, we analyzed serum 25(OH)D and
      pro-inflammatory cytokine concentrations prior to and serially after TKA in a
      case subject (female; age, 62 year; height, 160 cm; body mass, 63 kg; body mass
      index, 26.5 kg/m(2)). The subtle decrease (12%) from pre-surgery to 2-d post
      surgery and the more pronounced decrease (74%) from 3-week to 8-week post-surgery
      in serum 25(OH)D concentrations corresponded with the increase in serum pro
      inflammatory cytokine (i.e., TNF-alpha, IFN-gamma, IL-1beta, GM-CSF, and IL-6)
      concentrations. This observation lends credence to the proposed hypothesis that
      pro-inflammatory cytokines could contribute to the decrease in serum 25(OH)D
      concentrations after TKA. Clearly, future research is needed to confirm the
      proposed hypothesis and to identify if attenuating the decrease in serum 25(OH)D
      concentrations improves patient outcomes after TKA.

PMID- 24332534
TI  - Additional evidence supporting the view of the neural signal as a propagating
      density pulse--A comment on Barz et al. (2013).

PMID- 24332535
TI  - CABP4 mutations do not cause congenital stationary night blindness.

PMID- 24332536
TI  - Incidence of visual improvement in uveitis cases with visual impairment caused by
      macular edema.
AB  - PURPOSE: Among cases of visually significant uveitic macular edema (ME), to
      estimate the incidence of visual improvement and identify predictive factors.
      DESIGN: Retrospective cohort study. PARTICIPANTS: Eyes with uveitis, seen at 5
      academic ocular inflammation centers in the United States, for which ME was
      documented to be currently present and the principal cause of reduced visual
      acuity (<20/40). METHODS: Data were obtained by standardized chart review. MAIN
      OUTCOME MEASURES: Decrease of >= 0.2 base 10 logarithm of visual acuity decimal
      fraction-equivalent; risk factors for such visual improvement. RESULTS: We
      identified 1510 eyes (of 1077 patients) with visual impairment to a level <20/40
      attributed to ME. Most patients were female (67%) and white (76%), and had
      bilateral uveitis (82%). The estimated 6-month incidence of >= 2 lines of visual
      acuity improvement in affected eyes was 52% (95% confidence interval [CI], 49%
      55%). Vision reduced by ME was more likely to improve by 2 lines in eyes
      initially with poor visual acuity (<= 20/200; adjusted hazard ratio [HR] 1.5; 95%
      CI, 1.3-1.7), active uveitis (HR, 1.3; 95% CI, 1.1-1.5), and anterior uveitis as
      opposed to intermediate (HR, 1.2), posterior (HR, 1.3), or panuveitis (HR, 1.4;
      overall P = 0.02). During follow-up, reductions in anterior chamber or vitreous
      cellular activity or in vitreous haze each led to significant improvements in
      visual outcome (P <0.001 for each). Conversely, snowbanking (HR, 0.7; 95% CI, 0.4
      0.99), posterior synechiae (HR, 0.8; 95% CI, 0.6-0.9), and hypotony (HR, 0.2; 95%
      CI, 0.06-0.5) each were associated with lower incidence of visual improvement
      with respect to eyes lacking each of these attributes at a given visit.
      CONCLUSIONS: These results suggest that many, but not all, patients with ME
      causing low vision in a tertiary care setting will enjoy meaningful visual
      recovery in response to treatment. Evidence of significant ocular damage from
      inflammation (posterior synechiae and hypotony) portends a lower incidence of
      visual recovery. Better control of anterior chamber or vitreous activity is
      associated with a greater incidence of visual improvement, supporting an
      aggressive anti-inflammatory treatment approach for ME cases with active
      inflammation.

PMID- 24332537
TI  - Incidence and progression of reticular drusen in age-related macular
      degeneration: findings from an older Australian cohort.
AB  - PURPOSE: To assess the 15-year incidence and progression of reticular drusen and
      associations of this lesion with age-related macular degeneration (AMD) risk
      factors. DESIGN: Population-based cohort. PARTICIPANTS: Blue Mountains Eye Study
      participants (n = 3654) 49 years of age and older attended baseline examinations;
      of these, 75.8%, 76.7%, and 56.1% of survivors attended 5-year, 10-year, and 15
      year follow-up examinations, respectively. METHODS: Color retinal photographs
      were obtained and comprehensive questionnaires were administered at each visit,
      and DNA samples were genotyped. Fundus autofluorescence images were not
      available. Reticular drusen identified from photographs were confirmed with side
      by-side grading using the Wisconsin AMD grading protocol. Incidence was assessed
      using Kaplan-Meier product limit survival methods, controlling for competing risk
      of death. Associations between smoking, fish consumption, serum lipids, systemic
      and dietary factors, the CFH single nucleotide polymorphism (SNP) rs1061170 and
      ARMS2 SNP rs10490924, and the 15-year incidence of reticular drusen were analyzed
      in discrete logistic regression models. Generalized estimating equation models
      were used to analyze eye-specific relationships between these risk factors and 5
      year progression from reticular drusen to late AMD. MAIN OUTCOME MEASURES:
      Incidence and progression of reticular drusen. RESULTS: The 15-year cumulative
      incidence of reticular drusen was 4.0% (n = 95). Increasing age (per decade
      increase; odds ratio [OR], 3.4; 95% confidence interval [CI], 2.6-4.4), female
      sex (OR, 2.0; 95% CI, 1.3-3.2), and presence of risk alleles of CFH-rs1061170
      (OR, 1.8; 95% CI, 1.3-2.4) or ARMS2-rs10490924 (OR, 3.0; 95% CI, 2.1-4.4) were
      associated with higher reticular drusen incidence. Current smoking at baseline
      predicted higher reticular drusen incidence (OR 2.1, 95% CI 1.0-4.5) after
      adjusting for age, sex, CFH-rs1061170 and ARMS2-rs10490924 polymorphisms. Of 118
      eyes with reticular drusen, 40 (33.9%) developed late AMD over 5 years. A higher
      proportion of eyes with reticular drusen located outside versus within the
      macular area progressed to late AMD (50.0% vs. 37.8%). Dietary lutein-zeaxanthin
      intake was associated with decreased likelihood of progression from reticular
      drusen to late AMD (adjusted OR, 0.5; 95% CI, 0.3-1.0). CONCLUSIONS: Known AMD
      risk factors were associated with greater long-term risk of reticular drusen.
      Neither total area nor central location of reticular drusen predicted 5-year
      progression to late AMD. Increased consumption of lutein-zeaxanthin predicted a
      lower risk of progression.

PMID- 24332538
TI  - Re: Kaiser: Emerging therapies for neovascular age-related macular degeneration:
      drugs in the pipeline (Ophthalmology 2013;120:S11-S15).

PMID- 24332539
TI  - Vav1 as a central regulator of invadopodia assembly.
AB  - Invadopodia are protrusive structures used by tumor cells for degradation of the
      extracellular matrix to promote invasion [1]. Invadopodia formation and function
      are regulated by cytoskeletal-remodeling pathways and the oncogenic kinase Src.
      The guanine nucleotide exchange factor Vav1, which is an activator of Rho family
      GTPases, is ectopically expressed in many pancreatic cancers, where it promotes
      tumor cell survival and migration [2, 3]. We have now determined that Vav1 is
      also a potent regulator of matrix degradation by pancreatic tumor cells as
      depletion of Vav1 by siRNA-mediated knockdown inhibits the formation of
      invadopodia. This requires the exchange function of Vav1 toward the GTPase Cdc42,
      which is required for invadopodia assembly [4, 5]. In addition, we have
      determined that Src-mediated phosphorylation and activation of Vav1 are both
      required for, and, unexpectedly, sufficient for, invadopodia formation.
      Expression of Vav1 Y174F, which mimics its activated state, is a potent inducer
      of invadopodia formation through Cdc42, even in the absence of Src activation and
      phosphorylation of other Src substrates, such as cortactin. Thus, these data
      identify a novel mechanism by which Vav1 can enhance the tumorigenicity and
      invasive potential of cancer cells. These data suggest that Vav1 promotes the
      matrix-degrading processes underlying tumor cell migration and further, under
      conditions of ectopic Vav1 expression, that Vav1 is a central regulator and major
      driver of invasive matrix remodeling by pancreatic tumor cells.

PMID- 24332540
TI  - Solutions to the public goods dilemma in bacterial biofilms.
AB  - Bacteria frequently live in densely populated surface-bound communities, termed
      biofilms [1-4]. Biofilm-dwelling cells rely on secretion of extracellular
      substances to construct their communities and to capture nutrients from the
      environment [5]. Some secreted factors behave as cooperative public goods: they
      can be exploited by nonproducing cells [6-11]. The means by which public-good
      producing bacteria avert exploitation in biofilm environments are largely
      unknown. Using experiments with Vibrio cholerae, which secretes extracellular
      enzymes to digest its primary food source, the solid polymer chitin, we show that
      the public goods dilemma may be solved by two very different mechanisms: cells
      can produce thick biofilms that confine the goods to producers, or fluid flow can
      remove soluble products of chitin digestion, denying access to nonproducers. Both
      processes are unified by limiting the distance over which enzyme-secreting cells
      provide benefits to neighbors, resulting in preferential benefit to nearby
      clonemates and allowing kin selection to favor public good production. Our
      results demonstrate new mechanisms by which the physical conditions of natural
      habitats can interact with bacterial physiology to promote the evolution of
      cooperation.

PMID- 24332541
TI  - An ecological network of polysaccharide utilization among human intestinal
      symbionts.
AB  - BACKGROUND: The human intestine is colonized with trillions of microorganisms
      important to health and disease. There has been an intensive effort to catalog
      the species and genetic content of this microbial ecosystem. However, little is
      known of the ecological interactions between these microbes, a prerequisite to
      understanding the dynamics and stability of this host-associated microbial
      community. Here we perform a systematic investigation of public goods-based
      syntrophic interactions among the abundant human gut bacteria, the Bacteroidales.
      RESULTS: We find evidence for a rich interaction network based on the breakdown
      and use of polysaccharides. Species that utilize a particular polysaccharide
      (producers) liberate polysaccharide breakdown products (PBPs) that are consumed
      by other species unable to grow on the polysaccharide alone (recipients). Cross
      species gene addition experiments demonstrate that recipients can grow on a
      polysaccharide if the producer-derived glycoside hydrolase, responsible for PBP
      generation, is provided. These producer-derived glycoside hydrolases are public
      goods transported extracellularly in outer membrane vesicles allowing for the
      creation of PBP and concomitant recipient growth spatially distant from the
      producer. Recipients can exploit these ecological interactions and conditionally
      outgrow producers. Finally, we show that these public goods-based interactions
      occur among Bacteroidales species coresident within a natural human intestinal
      community. CONCLUSIONS: This study examines public goods-based syntrophic
      interactions between bacterial members of the human gut microbial ecosystem. This
      polysaccharide-based network likely represents foundational relationships
      creating organized ecological units within the intestinal microbiota, knowledge
      of which can be applied to impact human health.

PMID- 24332542
TI  - cis-regulatory requirements for tissue-specific programs of the circadian clock.
AB  - BACKGROUND: Broadly expressed transcriptions factors (TFs) control tissue
      specific programs of gene expression through interactions with local TF networks.
      A prime example is the circadian clock: although the conserved TFs CLOCK (CLK)
      and CYCLE (CYC) control a transcriptional circuit throughout animal bodies,
      rhythms in behavior and physiology are generated tissue specifically. Yet, how
      CLK and CYC determine tissue-specific clock programs has remained unclear.
      RESULTS: Here, we use a functional genomics approach to determine the cis
      regulatory requirements for clock specificity. We first determine CLK and CYC
      genome-wide binding targets in heads and bodies by ChIP-seq and show that they
      have distinct DNA targets in the two tissue contexts. Computational dissection of
      CLK/CYC context-specific binding sites reveals sequence motifs for putative
      partner factors, which are predictive for individual binding sites. Among them,
      we show that the opa and GATA motifs, differentially enriched in head and body
      binding sites respectively, can be bound by OPA and SERPENT (SRP). They act
      synergistically with CLK/CYC in the Drosophila feedback loop, suggesting that
      they help to determine their direct targets and therefore orchestrate tissue
      specific clock outputs. In addition, using in vivo transgenic assays, we validate
      that GATA motifs are required for proper tissue-specific gene expression in the
      adult fat body, midgut, and Malpighian tubules, revealing a cis-regulatory
      signature for enhancers of the peripheral circadian clock. CONCLUSIONS: Our
      results reveal how universal clock circuits can regulate tissue-specific rhythms
      and, more generally, provide insights into the mechanism by which universal TFs
      can be modulated to drive tissue-specific programs of gene expression.

PMID- 24332543
TI  - Optogenetic and electrical microstimulation systematically bias visuospatial
      choice in primates.
AB  - Optogenetics is a recently developed method in which neurons are genetically
      modified to express membrane proteins sensitive to light, enabling precisely
      targeted control of neural activity [1-3]. The temporal and spatial precision
      afforded by neural stimulation by light holds promise as a powerful alternative
      to current methods of neural control, which rely predominantly on electrical and
      pharmacological methods, in both research and clinical settings [4, 5]. Although
      the optogenetic approach has been widely used in rodent and other small animal
      models to study neural circuitry [6-8], its functional application in primate
      models has proven more difficult. In contrast to the relatively large literature
      on the effects of cortical electrical microstimulation in perceptual and decision
      making tasks [9-13], previous studies of optogenetic stimulation in primates have
      not demonstrated its utility in similar paradigms [14-18]. In this study, we
      directly compare the effects of optogenetic activation and electrical
      microstimulation in the lateral intraparietal area during a visuospatial
      discrimination task. We observed significant and predictable biases in visual
      attention in response to both forms of stimulation that are consistent with the
      experimental modulation of a visual salience map. Our results demonstrate the
      power of optogenetics as a viable alternative to electrical microstimulation for
      the precise dissection of the cortical pathways of high-level processes in the
      primate brain.

PMID- 24332544
TI  - Common origin of insect trachea and endocrine organs from a segmentally repeated
      precursor.
AB  - Segmented organisms have serially repeated structures [1] that become specialized
      in some segments [2]. We show here that the Drosophila corpora allata,
      prothoracic glands, and trachea have a homologous origin and can convert into
      each other. The tracheal epithelial tubes develop from ten trunk placodes [3, 4],
      and homologous ectodermal cells in the maxilla and labium form the corpora allata
      and the prothoracic glands. The early endocrine and trachea gene networks are
      similar, with STAT and Hox genes inducing their activation. The initial
      invagination of the trachea and the endocrine primordia is identical, but
      activation of Snail in the glands induces an epithelial-mesenchymal transition
      (EMT), after which the corpora allata and prothoracic gland primordia coalesce
      and migrate dorsally, joining the corpora cardiaca to form the ring gland. We
      propose that the arthropod ectodermal endocrine glands and respiratory organs
      arose through an extreme process of divergent evolution from a metameric repeated
      structure.

PMID- 24332545
TI  - Reward contexts extend dopamine signals to unrewarded stimuli.
AB  - Basic tenets of sensory processing emphasize the importance of accurate
      identification and discrimination of environmental objects [1]. Although this
      principle holds also for reward, the crucial acquisition of reward for survival
      would be aided by the capacity to detect objects whose rewarding properties may
      not be immediately apparent. Animal learning theory conceptualizes how unrewarded
      stimuli induce behavioral reactions in rewarded contexts due to
      pseudoconditioning and higher-order context conditioning [2-6]. We hypothesized
      that the underlying mechanisms may involve context-sensitive reward neurons. We
      studied short-latency activations of dopamine neurons to unrewarded, physically
      salient stimuli while systematically changing reward context. Dopamine neurons
      showed substantial activations to unrewarded stimuli and their conditioned
      stimuli in highly rewarded contexts. The activations decreased and often
      disappeared entirely with stepwise separation from rewarded contexts. The
      influence of reward context suggests that dopamine neurons respond to real and
      potential reward. The influence of reward context is compatible with the reward
      nature of phasic dopamine responses. The responses may facilitate rapid, default
      initiation of behavioral reactions in environments usually containing reward.
      Agents would encounter more and miss less reward, resulting in survival advantage
      and enhanced evolutionary fitness.

PMID- 24332546
TI  - The genome of the foraminiferan Reticulomyxa filosa.
AB  - BACKGROUND: Rhizaria are a major branch of eukaryote evolution with an extensive
      microfossil record, but only scarce molecular data are available. The rhizarian
      species Reticulomyxa filosa, belonging to the Foraminifera, is free-living in
      freshwater environments. In culture, it thrives only as a plasmodium with
      thousands of haploid nuclei in one cell. The R. filosa genome is the first
      foraminiferal genome to be deciphered. RESULTS: The genome is extremely
      repetitive, and the large amounts of identical sequences hint at frequent
      amplifications and homologous recombination events. Presumably, these mechanisms
      are employed to provide more gene copies for higher transcriptional activity and
      to build up a reservoir of gene diversification in certain gene families, such as
      the kinesin family. The gene repertoire indicates that it is able to switch to a
      single-celled, flagellated sexual state never observed in culture. Comparison to
      another rhizarian, the chlorarachniophyte alga Bigelowiella natans, reveals that
      proteins involved in signaling were likely drivers in establishing the Rhizaria
      lineage. Compared to some other protists, horizontal gene transfer is limited,
      but we found evidence of bacterial-to-eukaryote and eukaryote-to-eukaryote
      transfer events. CONCLUSIONS: The R. filosa genome exhibits a unique architecture
      with extensive repeat homogenization and gene amplification, which highlights its
      potential for diverse life-cycle stages. The ability of R. filosa to rapidly
      transport matter from the pseudopodia to the cell body may be supported by the
      high diversification of actin and kinesin gene family members.

PMID- 24332547
TI  - A mummified duck-billed dinosaur with a soft-tissue cock's comb.
AB  - Among living vertebrates, soft tissues are responsible for labile appendages
      (combs, wattles, proboscides) that are critical for activities ranging from
      locomotion to sexual display [1]. However, soft tissues rarely fossilize, and
      such soft-tissue appendages are unknown for many extinct taxa, including
      dinosaurs. Here we report a remarkable "mummified" specimen of the hadrosaurid
      dinosaur Edmontosaurus regalis from the latest Cretaceous Wapiti Formation,
      Alberta, Canada, that preserves a three-dimensional cranial crest (or "comb")
      composed entirely of soft tissue. Previously, crest function has centered on the
      hypertrophied nasal passages of lambeosaurine hadrosaurids, which acted as
      resonance chambers during vocalization [2-4]. The fleshy comb in Edmontosaurus
      necessitates an alternative explanation most likely related to either social
      signaling or sexual selection [5-7]. This discovery provides the first view of
      bizarre, soft-tissue signaling structures in a dinosaur and provides additional
      evidence for social behavior. Crest evolution within Hadrosaurinae apparently
      culminated in the secondary loss of the bony crest at the terminal Cretaceous;
      however, the new specimen indicates that cranial ornamentation was in fact not
      lost but substituted in Edmontosaurus by a fleshy display structure. It also
      implies that visual display played a key role in the evolution of hadrosaurine
      crests and raises the possibility of similar soft-tissue structures among other
      dinosaurs.

PMID- 24332548
TI  - Management of kidney disease in patients with diabetes in the primary care
      setting.
AB  - AIMS: To evaluate the performance of general practitioners (GPs) in the care of
      diabetic patients in areas represented or unrepresented by quality indicators.
      METHODS: An observational study in primary care practices. The study population
      was comprised of GPs who cared for 1799 patients with diabetes mellitus co
      existing with stage 3 chronic kidney disease, hypertension, and cardiovascular
      disease. The performance of GPs was monitored twice during a 6-month interval
      using a regional computerized clinical data base according to the measurement and
      treatment of blood pressure, LDL-cholesterol level, proteinuria, hematuria, and
      anemia. RESULTS: Those parameters which were familiar to the GPs for several
      years as part of the Quality Indicators Program (QIP) were measured and treated
      at a high rate compared to parameters not included in the QIP. For example,
      measurement of blood pressure and testing for glycosylated hemoglobin were 99%
      and 98% respectively at the end point. In contrast the rate of performance of
      specific kidney disease-focused activities, such as referral of patients with
      proteinuria to nephrologic consultation was 36% at the end point. CONCLUSION:
      Good performance in areas monitored by Quality Indicators does not imply good
      quality of care in other areas for the same patients. Attention should be paid to
      initiating activities to raise the awareness of GPs with respect to important
      health parameters which are not included in the Quality Indicators Program.

PMID- 24332549
TI  - E23K variant in KCNJ11 gene is associated with susceptibility to type 2 diabetes
      in the Mauritanian population.
AB  - AIMS: Many genetic association studies reported the contribution of KCNJ11 gene
      to type 2 diabetes susceptibility in different populations. We aimed to evaluate
      the association between E23K variant of KCNJ11 and type 2 diabetes in the
      Mauritanian population. MATERIALS AND METHODS: We performed a case-control
      association study including 135 type 2 diabetes Mauritanian patients and 135
      controls. Genotyping for the E23K variant was performed using a TaqMan allelic
      discrimination assay. RESULTS: We found significant association between KCNJ11
      E23K variant and type 2 diabetes (Global model, OR=2.08, 95% CI=1.09-3.97,
      p=0.026). In the Moor ethnic group, E23K was also associated with type 2 diabetes
      in the general model (OR=2.08, 95% CI=1.09-3.97, p=0.026) and under the dominant
      model (OR=2.49, 95% CI=1.12-5.55, p=0.026). In the Mauritanians of African
      descent, KK genotype was not found. Besides, E23K variant was not associated with
      type 2 diabetes (OR=0.69, 95% CI=0.04-11.32, p=0.793). CONCLUSIONS: Our results
      revealed the risk of type 2 diabetes conferred by KCNJ11 E23K gene variant in the
      Mauritanian population.

PMID- 24332550
TI  - Deficiency of Smad3 results in enhanced inducible nitric oxide synthase-mediated
      hypotension in lipopolysaccharide-induced endotoxemia.
AB  - BACKGROUND: Smad3 is a principal intracellular mediator of signaling for
      transforming growth factor beta, a cytokine involved in pleiotropic
      pathophysiological processes including inflammation and immunity. The function of
      Smad3 in regulating inducible nitric oxide synthase (iNOS) expression and septic
      shock has not been characterized. METHODS: Smad3(-/-) (referred hereafter as KO)
      and wild-type (WT) mice were injected intraperitoneally with lipopolysaccharide
      (LPS) to induce the septic hypotension. Mortality, blood pressure, and plasma
      levels of nitrite were measured. The iNOS messenger RNA and protein levels in
      lung, kidney, and spleen were also analyzed. RESULTS: Mice lacking functional
      Smad3 respond to LPS with greater mortality than their WT littermates. The high
      mortality of KO mice is accompanied by enhanced hypotension after intraperitoneal
      injection of LPS. Both KO and WT mice displayed an increase in plasma nitrite
      during the experimental period; however, LPS administration caused more dramatic
      changes in KO mice than WT mice. Likewise, the iNOS messenger RNA and protein
      levels in lung, kidney, and spleen were more strongly increased in KO mice than
      in WT mice after LPS administration. CONCLUSIONS: Defects in the Smad3 gene may
      increase susceptibility to the development of septic hypotension because of
      enhanced iNOS production.

PMID- 24332551
TI  - Comparison of surgical outcomes between papillary thyroid cancer patients treated
      with the Harmonic ACE scalpel and LigaSure Precise instrument during conventional
      thyroidectomy: a single-blind prospective randomized controlled trial.
AB  - BACKGROUND: The aim of this study was to evaluate the safety and efficacy of
      thyroidectomy using the Harmonic ACE scalpel (HS) or the LigaSure Precise (LS)
      instrument in conventional thyroidectomy. MATERIALS AND METHODS: A prospective,
      randomized controlled trial was performed. Between August 2011 and June 2012, 832
      patients who required thyroidectomy for papillary thyroid cancer were randomized
      into groups treated with either the HS or the LS instrument. Operative time and
      surgical morbidities were analyzed. RESULTS: A total of 320 patients (HS group, N
      = 164; LS instrument group, N = 156) were randomized for analysis according to
      the intention-to-treat principle. There were no statistically significant
      differences in the operative times (HS group versus LS instrument group: 71.93 +/
      18.26 versus 75.15 +/- 20.13; P = 0.423), postoperative transient
      hypoparathyroidism (13.4% versus 14.1%; P = 0.858), and permanent recurrent
      laryngeal nerve injuries between the two groups. CONCLUSIONS: In this study, both
      hemostatic devices were safe and effective in terms of postoperative results and
      complications without any differences.

PMID- 24332552
TI  - Involvement of transforming growth factor-beta3 and betaglycan in the
      cytoarchitecture of postoperative omental adhesions.
AB  - BACKGROUND: Adhesions commonly appear in patients after abdominal surgery, with
      considerable individual variation in adhesion composition and severity of the
      repair process. Here, we address the influence of transforming growth factor
      (TGF)-beta3 and betaglycan in this response, in relation to TGF-beta1, in an
      adhesiogenic rabbit model. MATERIALS AND METHODS: Omental adhesions were
      recovered 3, 7, 14, and 90 d after the implantation of a polypropylene mesh on
      the parietal peritoneum in New Zealand White rabbits. Omentum from nonoperated
      animals served as control. Tissue specimens were examined for TGF-beta3 and TGF
      beta1 (Western blotting, reverse transcription-polymerase chain reaction), and
      TGF-beta1:TGF-beta3 messenger RNA and protein expression ratios were analyzed.
      Immunohistochemical detection of TGF-beta3 and betaglycan was performed. RESULTS:
      Injury to the omentum led to mobilization of TGF-beta3 and betaglycan-expressing
      cells from milky spots. Fibrous zones in adhesions were simultaneous to the
      presence of TGF-beta1 and the membrane-bound form of betaglycan (7-d adhesions),
      whereas soluble betaglycan appeared in TGF-beta1-positive areas showing limited
      fibrosis (3-d adhesions). The elevated expression of TGF-beta3 concurrent with
      the presence of membrane-bound form of betaglycan was observed in zones of
      adipose regeneration (14-d adhesions), whereas zones of fibrous consistency were
      negative for TGF-beta3. CONCLUSIONS: Milky spots on the omentum contain
      inflammatory/immune cells positive for TGF-beta3, TGF-beta1, and betaglycan,
      playing a role in the damaged omentum repair. Our observations support the
      contribution of TGF-beta3 to tissue repair through adipose tissue regeneration
      and the profibrotic role of TGF-beta1 and suggest that these effects on the local
      wound repair response could be driven by the expression of betaglycan in its
      soluble or membrane-bound form.

PMID- 24332553
TI  - Fibrin patch in a pig model with blunt liver injury under severe hypothermia.
AB  - BACKGROUND: Rapid control of hemorrhage is one of the key aspects in trauma
      handling. To cope with bleeding, local hemostatic approaches are useful, along
      with surgical and systemic homostatic therapy. In this experimental study, we
      investigated the efficacy of a fibrinogen/thrombin containing collagen patch
      (TachoSil) in a coagulopathic pig model with blunt liver trauma under severe
      hypothermia. METHODS: Eighteen anesthetized pigs underwent hemodilution by
      exchanging 70% of the blood volume with Ringer Lactate solution and hydroxyethyl
      starch 130/0.4 (1:1). Ten minutes after induction of a grade III blunt liver
      trauma, the animals randomly received treatment with TachoSil (FT-patch, n = 9)
      or a collagen patch (Tachotop, control group, n = 9). Blood loss, hemodynamics,
      and coagulation parameters were observed for 2 h. To confirm the consistency of
      liver trauma, pathologic examination of the liver tissue was performed. RESULTS:
      Hypothermia (33.5 degrees C +/- 0.5 degrees C) and hemodilution led to severe
      coagulopathy as measured by thromboelastometry and coagulation parameters. After
      trauma and patch application, thromboelastometry and coagulation parameters in
      the control group showed further deterioration compared with the stable
      parameters in the FT-patch group. The total blood loss was significantly reduced
      in the FT-patch group (FT-patch: 1195 mL; control group: 2495 mL; P < 0.001).
      Concordantly, the control animals were hemodynamically jeopardized to a higher
      degree. Microscopy confirmed a similar degree of liver injury. CONCLUSIONS:
      Despite severe hypothermia and coagulopathy, TachoSil provided effective
      hemorrhage control in pigs with blunt liver injury. Therefore, TachoSil
      demonstrated usefulness as an additional early therapy in cases of uncontrolled
      bleeding following severe trauma.

PMID- 24332554
TI  - Colorectal cancer patient-derived xenografted tumors maintain characteristic
      features of the original tumors.
AB  - BACKGROUND: Despite significant improvements in colon cancer outcomes over the
      past few decades, preclinical development of more effective therapeutic
      strategies is still limited by the availability of clinically relevant animal
      models. To meet those clinical unmet needs, we generated a well-characterized in
      vivo preclinical platform for colorectal cancer using fresh surgical samples.
      METHODS: Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that
      originate from surgery were implanted into the subcutaneous space of nude mice
      and serially passaged in vivo. Mutation status, hematoxylin and eosin staining,
      short tandem repeat profiling, and array comparative genomic hybridization were
      used to validate the similarity of molecular characteristics between the patient
      tumors and tumors obtained from xenografts. RESULTS: From surgical specimens of
      143 patients, 97 xenograft models were obtained in immunodeficient mice
      (establish rate = 67%). Thirty-nine xenograft models were serially expanded
      further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 +/- 20
      d. Histologic and immunohistochemical analyses revealed a high degree of
      pathologic similarity including histologic architecture and expression of CEA,
      CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed
      that genetic mutations, genomic alterations, and gene expression patterns of each
      patient tumor were also well conserved in the corresponding xenograft tumor.
      CONCLUSIONS: Xenograft animal models derived from fresh surgical sample
      maintained the key characteristic features of the original tumors, suggesting
      that this in vivo platform can be useful for preclinical development of novel
      therapeutic approaches to colorectal cancers.

PMID- 24332555
TI  - Does diffusion-weighted imaging add diagnostic confidence in discriminating
      between benign and malignant solid focal liver lesions?
AB  - We investigated whether diffusion-weighted Imaging (DWI) adds diagnostic
      confidence in assessing focal liver lesions (FLLs). By reviewing FLLs without and
      with DWI at 1.5 T, two radiologists scored the confidence in diagnosing
      benignancy/malignancy (confidence score), and DWI usefulness (usefulness score).
      We showed that adding DWI significantly decreased the confidence score of the
      most experienced radiologist and increased his confidence in false-negative
      diagnoses showing atypical features on conventional magnetic resonance imaging. 

PMID- 24332556
TI  - IgG4-related systemic disease affecting the parotid and submandibular glands:
      magnetic resonance imaging features of IgG4-related chronic sclerosing
      sialadenitis and concomitant lymphadenitis.
AB  - BACKGROUND: IgG4-related systemic disease (IgG4-RSD) is a recently recognised
      fibroinflammatory condition, characterized by a tissue infiltration and/or
      enlargement and typical histopathological findings. METHODS AND RESULTS: We
      report on a 73-year-old male with bilateral preauricular swelling and a remote
      history of unexplained systemic disease. Magnetic resonance imaging showed
      enlargement of all major salivary glands and cervical lymph node due to a tissue
      infiltration with marked enhancement and restricted diffusion. Elevated serum
      IgG4 levels and histopathological findings on an excisional lymph node biopsy
      were consistent with IgG4-RSD. CONCLUSION: Magnetic resonance imaging seems to be
      a useful tool to support the diagnosis of IgG4-related systemic disease of
      salivary glands.

PMID- 24332557
TI  - The role of apparent diffusion coefficient values in differentiation between
      adrenal masses.
AB  - The aim of this study was to evaluate the utility of apparent diffusion
      coefficient (ADC) values in differentiation between solid adrenal masses. The ADC
      values of 73 adrenal lesions (54 benign, 19 malignant) in 69 patients were
      measured at b 100, 600 and 1000 gradients on diffusion-weighted magnetic
      resonance imaging (DW-MRI). No statistically significant difference was found
      between ADC values of benign and malignant adrenal masses, nonadenomatous benign
      adrenal masses and malignant adrenal masses, adrenal adenomas and nonadenomatous
      lesions, adenomas and metastases, adenomas and pheochromocytomas, metastases and
      pheochromocytomas. ADC values are not helpful in the differentiation between
      solid adrenal masses. 

PMID- 24332558
TI  - [Irisin: a messenger from the gods?].
AB  - Due to the need to understand the basis of the metabolic benefits of exercise,
      irisin was discovered a few years ago. This cytokine, secreted by skeletal muscle
      due to exercise, should have positive effects on energetic metabolism. In
      particular, it could act as a messenger on white adipose tissue, modifying its
      phenotype into the beige adipocyte, and increasing its thermogenic capacity.
      Since it was described, there have been numerous studies led to depict its
      function, with the aim of determining if irisin could become a therapeutic target
      in the context of diseases associated with a caloric excess, such as obesity and
      diabetes. In this review, the irisin discovery is summarized, along with its in
      vitro and in vivo effects described up until now. 

PMID- 24332559
TI  - Variation in use of estrogen receptor-alpha gene promoters in breast cancer
      compared by quantification of promoter-specific messenger RNA.
AB  - INTRODUCTION: Estrogen receptor (ER)-alpha expression offers a critical
      characterization of breast cancer, but risk of recurrence is difficult to predict
      using only ERalpha status. The ERalpha gene has at least 6 transcription start
      sites, 6 distinct first exons, and probably 6 promoters. To examine whether these
      promoters have differential effects in breast cancer, we quantified expression of
      promoter-specific ERalpha messenger RNA (mRNA), using real-time polymerase chain
      reaction (PCR) and statistical assessment. PATIENTS AND METHODS: We examined
      variations in the use of breast cancer cell lines and 43 ERalpha positive
      (ERalpha(+)) breast cancer tissue samples by quantifying promoter-specific mRNA
      of ERalpha with real-time PCR analysis using primers and probes specially
      designed for this study. Moreover, we correlated the results of quantified the
      promoter-specific mRNA with mRNA of total ERalpha and related them to
      clinicopathological factors statistically. We also examined multiregression
      analyses for promoter-specific mRNAs of ERalpha. RESULT: We found the promoters
      to be used at almost similar ratios among ERalpha(+) breast cancer cell lines and
      ERalpha(+) breast cancer tissues. Clinicopathological variations were associated
      with identical ERalpha promoter choices. When we examined the contribution of
      mRNA from 3 promoters in breast cancer tissues to total ERalpha using multiple
      regression analysis, we found that only promoter A showed a significant (P < .05)
      transcript coefficient. CONCLUSION: Our findings imply that the use of ERalpha
      promoters as prognostic biomarkers is unfeasible. However, our results suggest
      that promoter usage of ERalpha may contribute to its expression in normal
      development and differentiation of individual or carcinogenesis of breast cancer.

PMID- 24332560
TI  - Idiopathic intracranial hypertension: descriptive analysis in our setting.
AB  - INTRODUCTION: Idiopathic intracranial hypertension is a disorder characterised by
      increased intracranial pressure without evidence of an expansive intracranial
      process or cerebrospinal fluid cytochemical alterations. PATIENTS AND METHOD: We
      reviewed the medical records of patients with idiopathic intracranial
      hypertension admitted to our hospital between 1999 and 2009 and who met the
      modified Dandy criteria. We collected the following data: age, body mass index
      (BMI), outlet pressure of cerebrospinal fluid, cardiovascular history, imaging
      studies, treatment, and outcome. RESULTS: We analysed 61 patients (19 males and
      42 females) with a mean age of 35.38 years. A BMI above the normal range was
      determined for 72.13% of the patients, although 47.37% of males showed normal
      weight. Fifty per cent of patients had a cardiovascular risk factor, especially
      dyslipidaemia, hypertension, and contraceptive drugs in women. Headache was the
      main presenting symptom, followed by visual field defects and other visual
      disturbances. Bilateral papilledema was present in 81.96% of the patients.
      CONCLUSIONS: The approximate incidence is 1.2/100,000 individuals/year. The
      condition is more common in young women with higher body weight and it is also
      associated with contraceptive drugs. Headache with bilateral papilloedema and
      impaired visual acuity stand out as the main symptoms. An interesting finding
      from this study is that male patients had a lower BMI, a lower incidence of
      headache and increased visual impairment.

PMID- 24332561
TI  - Vincent van Gogh: a pathographic analysis.
AB  - The life and artistic legacy of Vincent van Gogh has generated great interest
      among physicians from different areas of specialization in proposing a
      retrospective differential diagnosis. The aim of the present study is to present
      a systematic pathographic analysis of the artist and to suggest a diagnosis
      consistent with the extant evidence. To this end, the available evidence is
      classified into five types: type I evidence (clinical opinion of an attending
      physician), type II evidence (description of symptoms in correspondence), type
      III evidence (historical accounts from first-hand sources or direct observation),
      type IV evidence (interpretation of the artist's work) and type V evidence
      (family medical history). Three basic prerequisites for a successful analysis
      are: (1) consideration of type II, III and V evidence as carrying the greatest
      pathographic weight, (2) consideration of the course of symptoms over time as a
      key element in the analysis, and (3) consideration of a single diagnostic
      hypothesis as the most probable explanation. After reviewing the available
      evidence in the light of these criteria, the author supports the diagnosis of
      acute intermittent porphyria (AIP) as the most likely cause of van Gogh's
      ailment. 

PMID- 24332563
TI  - Obsessive-compulsive disorder and gut microbiota dysregulation.
AB  - Obsessive-compulsive disorder (OCD) is a debilitating disorder for which the
      cause is not known and treatment options are modestly beneficial. A hypothesis is
      presented wherein the root cause of OCD is proposed to be a dysfunction of the
      gut microbiome constituency resulting in a susceptibility to obsessional
      thinking. Both stress and antibiotics are proposed as mechanisms by which gut
      microbiota are altered preceding the onset of OCD symptomology. In this light,
      pediatric autoimmune neuropsychiatric disorders associated with streptococcal
      infections (PANDAS) leading to episodic OCD is explained not by group A beta
      hemolytic streptococcal infections, but rather by prophylactic antibiotics that
      are administered as treatment. Further, stressful life events known to trigger
      OCD, such as pregnancy, are recast to show the possibility of altering gut
      microbiota prior to onset of OCD symptoms. Suggested treatment for OCD would be
      the directed, specie-specific (re)introduction of beneficial bacteria modifying
      the gut microbiome, thereby ameliorating OCD symptoms. Special considerations
      should be contemplated when considering efficacy of treatment, particularly the
      unhealthy coping strategies often observed in patients with chronic OCD that may
      need addressing in conjunction with microbiome remediation. 

PMID- 24332562
TI  - Insulin-associated neuroinflammatory pathways as therapeutic targets for
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) is characterized by an abrupt blow or exchange of
      force against the head and can be categorized as mild, moderate, and severe. The
      secondary cell death after TBI displays ischemic-like patterns including
      neuroinflammation. The scavenger receptor cluster of differentiation (CD) 36 is a
      lipid-associated protein capable of transducing intracellular signals to promote
      inflammatory mechanisms within different cell types. Expression and activation of
      CD36 is closely related to dyslipidemia secondary to diabetes. Diabetes mellitus
      (DM) has been documented as a co-morbidity factor in TBI, in that patients with a
      history of diabetes present with more severe brain damage and slower recovery
      from TBI than non-diabetic patients. Indeed, a strict regulation of blood serum
      glucose by the use of insulin promotes a better outcome for TBI patients. Based
      on these recent findings, we now advance the hypothesis that CD36 via DM insulin
      associated pathways is closely involved in TBI chronic pathology. 

PMID- 24332564
TI  - Pin1, endothelial nitric oxide synthase, and amyloid-beta form a feedback
      signaling loop involved in the pathogenesis of Alzheimer's disease, hypertension,
      and cerebral amyloid angiopathy.
AB  - Although the molecular mechanism has not yet been clarified until now, it is very
      interesting that Alzheimer's disease (AD), hypertension (HTN), and cerebral
      amyloid angiopathy (CAA) often occur synchronously and possess many similar
      pathological characteristics. Herein, we hypothesize that a feedback signaling
      loop, consisted of Pin1, endothelial nitric oxide synthase (eNOS), and amyloid
      beta (Abeta), may contribute to the interesting pathological phenomenon. First,
      Pin1 inhibits the production of Abeta, and enhances the activity of eNOS. Second,
      Abeta and eNOS form a mutual inhibition system. Third, the well-balanced feedback
      signaling loop avoids the development of AD, HTN, and CAA by inhibiting the
      frequent pathological characteristics of these diseases, including Abeta
      deposition in cerebral microvessels and cerebral microbleeds. On one hand, Pin1
      and eNOS not only inhibit Abeta production but also accelerate Abeta clearance,
      preventing Abeta deposition in cerebral microvessels. On the other hand, Pin1 and
      eNOS promote vasodilatation and prevent the elevation of blood pressure in brain,
      alleviating the pathology of cerebral microbleeds. However, once the precise
      balance is disturbed, it may result in Abeta deposition, microbleeds, and
      elevated blood pressure, possibly leading to the synchronous occurrence of AD,
      HTN, and CAA. The hypothesis updates the current understanding of the molecular
      linkage among AD, HTN, and CAA, and lays the ground for developing combined
      prevention, diagnosis, and treatment of these diseases more efficiently and more
      economically. Interestingly, biotechnical medicines enhancing the activity of
      Pin1 and/or eNOS may prevent the development of AD, HTN, and CAA, and targeting
      Abeta deposition may alleviate the clinical pathologies of these related
      diseases.

PMID- 24332565
TI  - Sleep and sadness: exploring the relation among sleep, cognitive control, and
      depressive symptoms in young adults.
AB  - BACKGROUND: Sleep disturbance is a common feature of depression. However, recent
      work has found that individuals who are vulnerable to depression report poorer
      sleep quality compared to their low-risk counterparts, suggesting that sleep
      disturbance may precede depression. In addition, both sleep disturbance and
      depression are related to deficits in cognitive control processes. Thus we
      examined if poor sleep quality predicts subsequent increases in depressive
      symptoms and if levels of cognitive control mediated this relation. METHODS:
      Thirty-five undergraduate students participated in two experimental sessions
      separated by 3 weeks. Participants wore an actigraph watch between sessions,
      which provided an objective measure of sleep patterns. We assessed self-reported
      sleep quality and depressive symptoms at both sessions. Last, individuals
      completed an exogenous cuing task, which measured ability to disengage attention
      from neutral and negative stimuli during the second session. RESULTS: Using path
      analyses, we found that both greater self-reported sleep difficulty and more
      objective sleep stability measures significantly predicted greater difficulty
      disengaging attention (i.e., less cognitive control) from negative stimuli. Less
      cognitive control over negative stimuli in turn predicted increased depression
      symptoms at the second session. Exploratory associations among the circadian
      locomotor output cycles kaput gene, CLOCK, single nucleotide polymorphism (SNP),
      rs11932595, as well as sleep assessments and depressive symptoms also are
      presented. CONCLUSIONS: These preliminary results suggest that sleep disruptions
      may contribute to increases in depressive symptoms via their impact on cognitive
      control. Further, variation in the CLOCK gene may be associated with sleep
      quality.

PMID- 24332567
TI  - [Incidence, hospital stay and risk factors associated with the occurrence of
      pharyngo-cutaneous fistula after total laryngectomy].
AB  - INTRODUCTION AND OBJECTIVES: Pharyngo-cutaneous fistula (PCF) is one of the main
      problems for patients undergoing total laryngectomy. There are many risk factors
      described and associated with the appearance of PCF; however, some of these are
      currently under discussion. The aim of this work is to analyse the incidence of
      PCF, hospital stay and associated risk factors in patients undergoing total
      laryngectomy in a secondary hospital. METHODS: This was an observational study in
      a retrospective cohort. We included all patients who underwent total laryngectomy
      between 2006 and 2011. We considered sociodemographic and clinical items, and
      most of the risk factors studied in the literature by other authors
      (tracheostomy, tumour stage, chemotherapy or radiotherapy before surgery, etc.).
      Statistical analyses were performed using SPSS((r)) 15.0 and Epidat((r)) 3.1.
      RESULTS: We analysed 70 total laryngectomies. The incidence of PCF in the time
      period studied was 48.6%. There were significant differences between the mean
      hospital stay of patients with and without PCF. Affected locoregional lymph nodes
      were found to be the only risk factor for the occurrence of PCF [RR=1.60 (1.006
      2.54)]. CONCLUSION: The incidence of PCF is associated with the presence of
      affected locoregional lymph nodes. It is not associated with tracheostomy,
      administration of radio/chemotherapy before surgery or tumour location.

PMID- 24332566
TI  - Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression
      by cardiac parasympathetic neurons.
AB  - Postganglionic cardiac parasympathetic and sympathetic nerves are physically
      proximate in atrial cardiac tissue allowing reciprocal inhibition of
      neurotransmitter release, depending on demands from central cardiovascular
      centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons
      synthesize and release the sympathetic neurotrophin nerve growth factor (NGF),
      which may serve to maintain these close connections. In this study we
      investigated whether NGF synthesis by CG neurons is altered in heart failure, and
      whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and
      proNGF immunoreactivity in CG neurons in heart failure rats following chronic
      coronary artery ligation was investigated. NGF immunoreactivity was decreased
      significantly in heart failure rats compared to sham-operated animals, whereas
      proNGF expression was unchanged. Changes in neurochemistry of CG neurons included
      attenuated expression of the cholinergic marker vesicular acetylcholine
      transporter, and increased expression of the neuropeptide vasoactive intestinal
      polypeptide. To further investigate norepinephrine's role in promoting NGF
      synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists.
      An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (beta
      AR agonist) treatment, which increased an additional 22% at 24h. Antagonist
      treatment blocked isoproterenol-induced increases in NGF transcripts. In
      contrast, the alpha-AR agonist phenylephrine did not alter NGF mRNA expression.
      These results are consistent with beta-AR mediated maintenance of NGF synthesis
      in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may
      potentially contribute to reduced connections with adjacent sympathetic nerves. 

PMID- 24332568
TI  - VH1-44 gene usage defines a subset of canine B-cell lymphomas associated with
      better patient survival.
AB  - The use of specific immunoglobulin heavy chain variable region (VH) genes has
      been associated with increased patient survival in human B-cell lymphomas (hBCL).
      Given the similarity of human and canine BCL (cBCL) in morphology and clinical
      treatment, we examined the choice of VH in cBCL and determined whether VH gene
      selection was a distinct feature associated with survival time in dogs. VH gene
      selection and mutational status in 52 cBCL, including 29 diffuse large B-cell
      lymphomas (cDLBCL, the most common subtype of cBCL), were analyzed by comparison
      with the 80 published canine germline VH gene sequences. We further examined the
      prognostic impact of the subgroups defined by these features on canine survival.
      We found that VH1-44 was preferentially expressed in the majority of the 52 cBCLs
      (60%) as well as in the majority of the cDLBCL subset (59%). VH1-44 gene
      expression was associated with a statistically better overall survival (p=0.039)
      in cBCL patients, as well as in the cDLBCL subset of patients (p=0.038). These
      findings suggest that VH gene selection in cBCL is not random and may therefore
      have functional implications for cBCL lymphomagenesis, in addition to being a
      useful prognostic biomarker.

PMID- 24332569
TI  - Evaluation of the effect of Benson's relaxation technique on pain and quality of
      life of haemodialysis patients: a randomized controlled trial.
AB  - BACKGROUND: Haemodialysis patients may suffer from pain and impairment of quality
      of life. Some complementary interventions, such as relaxation therapy, might
      affect the pain and quality of life. The present study aimed to identify the
      effectiveness of Benson's relaxation technique in relieving pain and improving
      the quality of life in haemodialysis patients. STUDY DESIGN: The study was a
      randomized controlled trial. SETTING AND PARTICIPANTS: The data were collected in
      two haemodialysis units affiliated to Shiraz University of Medical Sciences. A
      total of 86 haemodialysis patients were randomly assigned to either the
      intervention (receiving Benson's relaxation technique) or the control group
      (routine care) from 2011 to 2012. INTERVENTION: The patients in the intervention
      groups listened to the audiotape of relaxation technique twice a day each time
      for 20min for eight weeks. MEASUREMENTS AND OUTCOMES: The pain numeric rating
      scale and Ferrans and Powers Quality of Life Index-dialysis version questionnaire
      were completed at baseline and 8 weeks after the intervention. The data were
      analyzed using independent t-test and ANCOVA. RESULTS: The results of ANCOVA
      showed a significant difference between the intervention and the control group
      concerning the mean score of the intensity of pain (F=6.03, p=0.01). Moreover, a
      significant difference was found between the intervention and the control group
      regarding the total quality of life (F=10.20, p=0.002) and health-functioning
      (F=8.64, p=0.004), socioeconomic (F=12.45, p=0.001), and family (F=8.52, p=0.005)
      subscales of quality of life. CONCLUSION: These findings indicated that Benson's
      relaxation technique might relieve the intensity of pain and improve the quality
      of life in haemodialysis patients. Thus, Benson's relaxation technique could be
      used as part of the care practice for relieving the pain intensity and
      improvement of the quality of life in haemodialysis patients.

PMID- 24332570
TI  - A multifaceted educational intervention to prevent delirium in older inpatients:
      a before and after study.
AB  - BACKGROUND: Systematically targeting modifiable risk factors for delirium may
      reduce its incidence. However, research interventions have not become part of
      routine clinical practice. Particular approaches to the education of clinical
      staff may improve their practice and patient outcomes. OBJECTIVES: To evaluate
      the effectiveness of a multifaceted educational program in preventing delirium in
      hospitalised older patients and improving staff practice, knowledge and
      confidence. DESIGN: A before and after study. SETTING: A 22-bed general medical
      ward of a district hospital in Sydney, Australia. PARTICIPANTS: Patients were
      aged 65 years and over and not delirious upon admission. Of 568 eligible
      patients, 129 were recruited pre-intervention (3 withdrew initial consent) and
      129 patients post-intervention. METHODS: Prior to the intervention, in order to
      establish a baseline, patients were assessed early after admission and again at
      discharge. The intervention was a one-hour lecture on delirium focusing on
      prevention for medical and nursing staff followed by weekly interactive tutorials
      with delirium resource staff and ward modifications. Following the initial
      education session, data were gathered in a second group of medical ward patients
      at the same time-points to ascertain the effectiveness of the intervention. Pre
      and post-intervention data were analysed to determine change in staff objective
      knowledge and self-ratings of confidence and clinical practice in relation to
      delirium. The main outcome measures were incident delirium and change in staff
      practice, confidence and knowledge. RESULTS: The mean age of patients was 81. The
      pre and post-intervention groups were comparable, aside from greater co morbidity
      in the pre-intervention group (F(1, 253)=9.20, p=0.003). Post-intervention there
      was a significant reduction in incident delirium (19% vs. 10.1%, X(2)=4.14,
      p=0.042), and improved function on discharge (mean improvement 5.3 points,
      p<0.001, SD 13.31, 95% CI -7.61 to -2.97). Staff objective knowledge of delirium
      improved post-intervention and their confidence assessing and managing delirious
      patients. Staff addressed more risk factors for delirium post-intervention (8.1
      vs. 9.8, F(1, 253)=73.44, p<0.001). CONCLUSIONS: A low-cost educational
      intervention reduced the incidence of delirium and improved function in older
      medical patients and staff knowledge and practice addressing risk factors for
      delirium. The program is readily transferable to other settings, but requires
      replication due to limitations of the before and after design.

PMID- 24332571
TI  - Comparison of visual and automated assessment of tumour inflammatory infiltrates
      in patients with colorectal cancer.
AB  - BACKGROUND: Cancer-associated inflammation is increasingly recognised to be an
      important determinant of oncological outcome. In colorectal cancer, the presence
      of peri-tumoural inflammatory/lymphocytic infiltrates predicts improved survival.
      To date, these infiltrates, assessed visually on haematoxylin and eosin (H&E)
      stained sections, have failed to enter routine clinical practice, partly due to
      their subjective assessment and considerable inter-observer variation. The
      present study aims to develop an automated scoring method to enable consistent
      and reproducible assessment of tumour inflammatory infiltrates in colorectal
      cancer. METHODS: 154 colorectal cancer patients who underwent curative resection
      were included in the study. The local inflammatory infiltrate was assessed using
      the method described by Klintrup-Makinen. H&E tumour sections were uploaded to an
      image analysis programme (Slidepath, Leica Biosystems). An image analysis
      algorithm was developed to count the inflammatory cells at the invasive margin.
      The manual and automated assessments of the tumour inflammatory infiltrates were
      then compared. RESULTS: The automated inflammatory cell counts assessed using the
      freehand annotation method (p<0.001) and the rectangular box method (p<0.001)
      were significantly associated with both K-M score (p<0.001) and K-M grade
      (p<0.001). The inflammatory cell counts were divided using quartiles to group
      tumours with similar inflammatory cell densities. There was good agreement
      between the manual and automated scoring methods (intraclass correlation
      coefficient (ICC)=0.82). Similar to the visual K-M scoring system, the automated
      K-M classification of the inflammatory cell counts, using quartiles, was
      significantly associated with venous invasion (p<0.05) and modified Glasgow
      Prognostic Score (mGPS) (p?0.05). On univariate survival analysis, both automated
      K-M category (p<0.05) and automated K-M grade (p<0.005) were associated with
      cancer-specific survival. CONCLUSION: The results of the present study
      demonstrate that automated assessment effectively recapitulates the clinical
      value of visual assessment of the local inflammatory cell infiltrate at the
      invasive margin of colorectal tumours. In addition, it is possible to obtain an
      objective assessment of tumour inflammatory infiltrates using routinely stained
      H&E sections. An automated, computer-based scoring method is therefore a workable
      and cost-effective approach to clinical assessment of local immune cell
      infiltrates in colorectal cancer.

PMID- 24332572
TI  - A blood-based three-gene signature for the non-invasive detection of early human
      hepatocellular carcinoma.
AB  - BACKGROUND: Identifying early stages of disease in high-risk individuals for the
      development of hepatocellular carcinoma (HCC) would greatly improve the clinical
      outcomes of these individuals. The aim of this study was to develop a blood-based
      gene set that could identify early-stage HCC. METHODS: Comprehensive gene
      expression profiling of purified RNA of peripheral blood mononuclear cells (PBMC)
      was performed using microarrays. Gene signatures were developed through
      bioinformatics-driven approaches and their diagnostic value was evaluated by
      custom-designed, quantitative, multiplex polymerase chain reaction (PCR) assays.
      RESULTS: Bioinformatics-driven analysis of microarray data derived from PBMC RNA
      samples of patients with HCC (N=10), pancreatic cancer (N=3), gastric cancer
      (N=3) and 10 normal individuals identified six genes that were differentially
      expressed in HCC. Subsequent multiplex-PCR validation and univariate analyses
      performed with an independent cohort of 114 HCC patients, 48 normal individuals
      and 14 patients with chronic hepatitis B (CHB) validated that three genes, namely
      Chemokine (C-X-C motif) receptor 2 (CXCR2), C-C chemokine receptor type 2 (CCR2)
      and E1A-Binding Protein P400 (EP400), were able to identify HCC individually with
      accuracies of 82.4%, 78.4% and 65%, respectively. In combination, these three
      genes gave an area under the curve (AUC) of 0.96 (95% confidence interval (CI),
      0.93-0.99) using multivariate logistic regression and yielded a sensitivity of
      93% and a specificity of 89%. When these three genes were used in combination
      with alpha-fetoprotein (AFP) to predict HCC, the accuracy of predicting HCC
      improved slightly with an AUC of 0.99 (95% CI, 0.98-1.0), sensitivity of 93% and
      specificity of 95%. CONCLUSIONS: CXCR2, CCR2 and EP400 can provide a promising
      non-invasive multiplex PCR diagnostic assay to monitor high-risk individuals for
      the development of HCC.

PMID- 24332573
TI  - Efficacy and toxicity of sunitinib in patients with metastatic renal cell
      carcinoma with renal insufficiency.
AB  - BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) with renal
      insufficiency are generally excluded from clinical trials, despite their
      increasing numbers. Thus, we evaluated the efficacy and toxicity of sunitinib in
      such patients. PATIENTS AND METHODS: Korean patients with mRCC with renal
      insufficiency who had received sunitinib as first-line treatment between January
      2008 and May 2012 were included. Patient characteristics, clinical outcomes and
      toxicities were evaluated. Overall survival (OS) and progression-free survival
      (PFS) were determined according to the degree of renal impairment. RESULTS: The
      median age of the 34 patients evaluated was 66 years, 90% had an Eastern
      Cooperative Oncology Group performance status of 0 or 1 and the median glomerular
      filtration rate was 46.5 mL min(-1) . 1.73 m(-2) (range, 21.1-59.5). The starting
      sunitinib dose was 37.5 and 50mg for 12 and 22 patients, respectively. A 4-weeks
      on-2-weeks-off regimen was followed for 31 patients; a 2-weeks-on-2-weeks-off
      regimen, for one patient; and a daily regimen, for two patients. The best
      response was partial response in eight patients and stable disease in 12. Median
      OS and PFS times were 26.3 months (95% confidence interval [CI]: 17.1-35.3) and
      12.2 months (95% CI: 10.2-13.2), respectively. Common non-haematologic adverse
      events (AEs) were stomatitis, rash, general oedema and fatigue. The most common
      AEs of ? grade 3 severity were fatigue, neutropenia and thrombocytopenia.
      CONCLUSIONS: In patients with mRCC with renal insufficiency, sunitinib was
      efficacious and did not cause increased toxicity. Thus, clinicians should not
      hesitate to treat patients with mRCC with renal insufficiency with sunitinib.

PMID- 24332574
TI  - Optimal imaging sequence for staging in colorectal liver metastases: analysis of
      three hypothetical imaging strategies.
AB  - BACKGROUND: Computed tomography (CT), positron emission tomography CT (PET-CT)
      and magnetic resonance imaging (MRI) all play a role in the management of
      colorectal liver metastases (CRLM), but inappropriate over investigation can lead
      to delays in treatment and additional cost. This study aimed to determine the
      optimal sequence for pre-operative imaging pathway to minimise delays to
      treatment and healthcare costs. METHODS: All patients with colorectal liver
      metastases referred to a single tertiary liver specialist multidisciplinary team
      (MDT) between 2008 and 2011 were examined. Primary data of clinical and
      radiological outcomes of all patients were analysed. These data were used to
      construct and test 3 hypothetical imaging strategies - 'Upfront', 'Sequential'
      and 'Hybrid' models. RESULTS: Six hundred and forty four consecutive patients
      were included. One hundred and sixty five patients were excluded for curative
      resection following the initial CT review. Subsequently 167/433 patients did not
      proceed to hepatectomies. Eighty (47.9%) of these patients had extra-hepatic
      disease identified on PET-CT, and 29 were due to the exclusion by MRI liver. A
      resectable pattern of liver disease on initial CT did not exclude patients with
      occult disease on PET-CT. Based on cost analysis, assessment of initial CT,
      followed by MDT with subsequent PET-CT and MRI imaging thereafter (Hybrid model),
      was associated with the shortest time-to-decision and lowest cost. CONCLUSIONS:
      Resectable pattern of liver metastases should not solely be used to determine the
      application of PET-CT for staging. Hybrid model is associated with the lowest
      cost and shortest time-to-treatment.

PMID- 24332575
TI  - Role of topoisomerase I and thymidylate synthase expression in sporadic
      colorectal cancer: associations with clinicopathological and molecular features.
AB  - Topoisomerase I (Topo I) and thymidylate synthase (TS) are essential enzymes for
      the replication, transcription and repair of DNA, and are potential biomarkers in
      colorectal cancer (CRC). The aim of the study was to correlate the tissue
      expression of Topo I and TS in sporadic CRCs with relevant pathological and
      molecular features and patients' outcome. Topo I and TS expression was assessed
      by immunostaining in 112 consecutive primary CRCs. Increased expression of Topo I
      was found in 36% of tumors, preferentially rectal (50%) and with not otherwise
      specified (NOS) histology (44%). Topo I expression was associated with 18q
      allelic loss (LOH), (p=0.013), microsatellite stable phenotype (p=0.002) and
      normal expression of mismatch proteins hMLH1 and hMSH2 (p=0.0012 and p=0.02,
      respectively). High TS expression was found in 60% of tumors, more frequently in
      distal sites (62%) and with NOS histology (66%); no association with
      microsatellite instability was observed. Topo I seems to be involved in the
      chromosomal instability pathway of sporadic CRCs. Conversely, high TS expression
      is unlikely to affect the clinical behavior of microsatellite unstable CRCs. 

PMID- 24332576
TI  - Mercury (Hg) and oxidative stress status in healthy mothers and its effect on
      birth anthropometric measures.
AB  - This study was conducted to: (a) investigate the antagonistic interaction between
      selenium (Se) and mercury (Hg) in mothers and their newborns, (b) delineate the
      role of oxidative mechanisms induced by Hg exposure and (c) examine the
      protective effect of Se on Hg-induced oxidative stress and birth outcomes. Levels
      of Hg and Se were measured in umbilical cord blood and the placentas of 250
      healthy mothers who participated in a study between 2006 and 2006 assessing
      prenatal exposure various pollutants. Levels of malondialdehyde (MDA) in cord and
      maternal blood and of 8-hydroxy-2-deoxyguanosine in urine were measured for
      assessing oxidative stress. Tail moment (TM) in the comet assay, as a biomarker
      of DNA damage was measured in samples of cord and maternal blood. The mean Se
      levels in umbilical cord blood (67.618+/-12.897MUg/l) were lower than those
      reported in many countries, but none of the newborns had Se levels <20MUg/l (the
      threshold limit of Keshan disease). More than 80% of the newborns, though, had Se
      levels below the 80MUg/l needed for maximum glutathione peroxidase activity. Even
      though 18.6% of the newborns had levels of Hg >=5.8MUg/l (the reference dose of
      the Environmental Protection Agency), no relationship was observed with the
      biomarkers of oxidative stress. The mean placental Hg levels (0.056+/-0.075MUg/g
      dry wt.) were higher than those reported for newborns with abnormal fetal
      development. Our study also documented significant placental transfer of Hg and
      Se to the fetus. The Hg/Se molar ratio in both cord blood and placental tissue
      was well below 1. The average amount of Se in both matrices was approximately 50
      fold in molar excess over Hg. The molar excess of Se in the umbilical cord
      (0.843MUmol/l), however, was lower than in placental tissues (13.098MUmol/kg dry
      wt.). In further support of the relationships of Hg and Se on oxidative stress,
      we observed significantly lower levels of maternal MDA associated with Se levels
      in both cord blood and placental tissues and significantly higher TM levels
      associated with placental Hg in both newborns and their mothers. In contrast,
      Se/Hg molar ratios in placental tissues were positively associated with MDA and
      negatively with TM. The disproportion between Hg and Se might be influenced by
      the length of Hg exposure that in turn might affect Se bioavailability. Each
      birth anthropometric outcome was modeled as a function of Hg, Se and their
      interactions. After an adjustment for confounding variables, Hg in cord blood had
      a significantly positive rather than the expected negative association with crown
      heel length. Placental Hg was associated with reduced birth height. Both
      associations were independent of prematurity. The status of Se in newborns was
      positively associated with crown-heel length and placental weight, with and
      without preterm births, and with birth weight, but only without preterm births.
      In contrast, a lower cephalization index was correlated with Se levels in cord
      blood, which may be an indicator of a detrimental effect on health. Our study,
      however, revealed associations between significantly lower levels of placental Se
      and several birth anthropometric measures (head circumference, birth weight and
      birth height) but the significance disappeared after excluding preterm births.
      Regression analyses generally indicated either significant or marginally
      significant Hg-Se antagonistic interactions that may have moderated the toxic
      effect of Hg on head circumference and birth weight. This finding may be due to
      chance or residual confounding and so may not be clinically relevant, but it may
      also suggest that Hg, Se and Hg-Se interactions are important factors for
      understanding Hg-induced adverse birth outcomes. Additional research will be
      necessary to evaluate the biological impact of combined metals in the assessment
      of fetal growth and development. 

PMID- 24332577
TI  - Commitment strength, alcohol dependence and HealthCall participation: effects on
      drinking reduction in HIV patients.
AB  - BACKGROUND: The role of three factors in drinking outcome after brief
      intervention among heavily drinking HIV patients were investigated: strength of
      commitment to change drinking, alcohol dependence, and treatment type: brief
      Motivational Interview (MI) only, or MI plus HealthCall, a technological
      extension of brief intervention. METHODS: HIV primary care patients (N=139) who
      drank >=4 drinks at least once in the 30 days before study entry participated in
      MI-only or MI+HealthCall in a randomized trial to reduce drinking. Patients were
      95.0% minority; 23.0% female; 46.8% alcohol dependent; mean age 46.3. Outcome at
      end of treatment (60 days) was drinks per drinking day (Timeline Follow-Back).
      Commitment strength (CS) was rated from MI session recordings. RESULTS: Overall,
      stronger CS predicted end-of-treatment drinking (p<.001). After finding an
      interaction of treatment, CS and alcohol dependence (p=.01), we examined
      treatment*CS interactions in alcohol dependent and non-dependent patients. In
      alcohol dependent patients, the treatment*commitment strength interaction was
      significant (p=.006); patients with low commitment strength had better outcomes
      in MI+HealthCall than in MI-only (lower mean drinks per drinking day; 3.5 and 4.6
      drinks, respectively). In non-dependent patients, neither treatment nor CS
      predicted outcome. CONCLUSIONS: Among alcohol dependent HIV patients, HealthCall
      was most beneficial in drinking reduction when MI ended with low commitment
      strength. HealthCall may not merely extend MI effects, but add effects of its own
      that compensate for low commitment strength. Thus, HealthCall may also be
      effective when paired with briefer interventions requiring less skill, training
      and supervision than MI. Replication is warranted.

PMID- 24332578
TI  - Marked differences of haplotype tagging SNP distribution, linkage, and haplotype
      profile of IL23 receptor gene in Roma and Hungarian population samples.
AB  - Polymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play
      an important role in the development of several autoimmune diseases. We examined
      five susceptible (rs10889677, rs1004819, rs2201841, rs11805303, rs11209032), one
      protective (rs7517847) and two neutral variants (rs7530511, rs1884444) of the
      IL23R gene in pooled DNA of healthy Roma (Gipsy) and Hungarian population
      samples. Our aim was to determine the genetic variability of the major haplotype
      tagging polymorphisms, and the haplotype profile of IL23R between the two groups.
      We analyzed 273 healthy Roma and 253 Hungarian DNA samples using PCR/RFLP assay.
      Comparing the five susceptible conferring alleles, there were significant
      increase (p<0.05), while in the protective alleles, there were decrease in the
      allele frequencies in Roma population (p<0.05). One of the neutral alleles showed
      increase, the another one did not differ between the two groups. The haplotype
      analysis of the SNPs revealed fundamentally different association types of SNPs
      in the two groups; moreover, the frequencies of the various haplotypes also
      exhibited strong differences, as of ht4 and ht5 haplotypes were significantly
      higher, whereas the frequencies of ht2 and ht3 haplotypes were significantly
      lower in the Roma population than in Hungarians (p<0.05). The data presented here
      show profound differences in the IL23R genetic profiles in the Roma population,
      that likely has also clinical implications in respect their possible role in the
      development of certain immunological diseases. 

PMID- 24332579
TI  - Case-control study of rhinoconjunctivitis associated with IL5RA polymorphisms in
      Japanese women: the Kyushu Okinawa Maternal and Child Health Study.
AB  - BACKGROUND: Epidemiological research on the relationship between single
      nucleotide polymorphisms (SNPs) in the IL5RA gene and allergic disorders is
      limited. We examined the relationship between IL5RA SNPs and risk of
      rhinoconjunctivitis in young adult Japanese women. METHODS: Included were 393
      women who met the criteria of the International Study of Asthma and Allergies in
      Childhood (ISAAC) for rhinoconjunctivitis. Controls were 767 women without
      rhinoconjunctivitis according to the ISAAC criteria who had not been diagnosed
      with allergic rhinitis by a doctor. Adjustment was made for age, region of
      residence, presence of older siblings, smoking, and education. RESULTS: Compared
      with the CC genotype of SNP rs6771148, the CG genotype, but not the GG genotype,
      was significantly associated with a reduced risk of rhinoconjunctivitis: the
      adjusted OR for the CG genotype was 0.76 (95% CI: 0.58-0.99). No evident
      associations were found between SNPs rs17882210, rs3804797, rs334809, rs9831572,
      or rs17881144 and rhinoconjunctivitis. The ACTAGA haplotype of rs17882210,
      rs3804797, rs334809, rs9831572, rs6771148, and rs17881144 was significantly
      inversely associated with rhinoconjunctivitis (crude OR=0.58, 95% CI: 0.37-0.88)
      while the GTAGCA haplotype was significantly positively related to
      rhinoconjunctivitis (crude OR=1.74, 95% CI: 1.14-2.65). No significant
      interactions affecting rhinoconjunctivitis were observed between any of the six
      SNPs and smoking. CONCLUSION: This is the first study to show significant
      associations between IL5RA SNP rs6771148, the ACTAGA haplotype, and the GTAGCA
      haplotype and the risk of rhinoconjunctivitis. We did not find evidence for
      interactions affecting rhinoconjunctivitis between any of the IL5RA SNPs and
      smoking.

PMID- 24332580
TI  - Surgical resection of primary tumour improves aerobic performance in colorectal
      cancer.
AB  - BACKGROUND: Colorectal cancer is the third most common cancer in the UK, with
      patients suffering declines in muscle mass and aerobic function. We hypothesised
      that tumour removal in non-metastatic colorectal cancer would lead to a
      restoration of lean muscle mass and increases in objective and subjective
      measures of aerobic performance. METHODS: We recruited two groups: patients with
      colorectal cancer (n = 30, 65.3 (51-77) y, body mass index 27.67 (4.83) kg m(-2))
      and matched controls (n = 30, 64.6 (42-77) y, BMI 27.14 (3.51) kg m(-2)).
      Controls underwent a single study while colorectal cancer patients were studied
      before and 10 months after tumour resection. Aerobic performance was assessed via
      cardiopulmonary exercise testing and activity questionnaires. Lean muscle mass
      was measured via dual-energy X-ray absorptiometry. RESULTS: Lean muscle mass was
      not different between groups (control: 47.82 (8.23); pre-resection: 52.41
      (10.59); post-resection: 52.38 (10.52), kg). Anaerobic threshold was lower in pre
      operative patients compared to controls (14.40 (3.23) vs. 19.67 (5.81) ml kg(-1)
      min(-1), p < 0.0001), increasing significantly post-resection (17.00 (3.56) ml
      kg(-1) min(-1)p < 0.0001). Self reported maximal physical activity was lower
      after resection compared to preoperatively (pre-resection 6.0 (6.5-5 IQR), post
      resection 3.75 (4-3 IQR), p < 0.0001). CONCLUSION: In colorectal cancer,
      anaerobic threshold is reached more rapidly than in matched controls, returning
      toward normal with tumour resection. Self-reported measures of activity do not
      mirror this objective change, cardiopulmonary exercise testing may therefore
      allow for a more accurate evaluation of pre and postoperative performance
      capability. The variance between objective and subjective measures of exercise
      capacity may be important in determining return to normal activities.

PMID- 24332581
TI  - Comparison of mammographic findings after intraoperative radiotherapy or external
      beam whole breast radiotherapy.
AB  - BACKGROUND: The TARGIT (TARGeted Intraoperative Radiotherapy) trial was designed
      to compare local recurrence and complication rates in breast cancer patients,
      prospectively randomised to either EBRT (external beam whole breast radiotherapy)
      or a single dose of IORT (intraoperative radiotherapy). The aim of our study was
      to compare follow-up mammographic findings, ultrasound and biopsy rates in each
      group. METHODS: Follow-up imaging and breast biopsies of women from one centre
      participating in the TARGIT-A trial were independently reviewed by two
      radiologists blinded to the radiotherapy treatment received. RESULTS: The cohort
      consisted of 141 patients (EBRT n = 80/IORT n = 61). There was no significant
      difference in the patient or disease characteristics of the two groups. The
      number of follow-up mammograms and length of follow-up was similar (EBRT/IORT n =
      2.0/2.4; 4.3yr/5.1yr; p = 0.386 chi(2) test). There were no significant
      differences in mammographic scar or calcification appearances of the post
      operative site. Generalised increase in breast density and skin thickening were
      more common in the EBRT compared to the IORT group (p = 0.002; p = 0.030, chi(2)
      test respectively). A trend towards additional ultrasound at follow-up was
      observed in the IORT group (15 of 61 [24.6%] versus 11 of 80 [13.8%]), however
      this was not statistically significant (p = 0.100 chi(2) test). No disease
      recurrence was demonstrated on any of the breast biopsies taken. Only one biopsy
      was reported as fat necrosis in the IORT group. CONCLUSIONS: Mammographic changes
      were more common following EBRT, although more additional follow-up ultrasounds
      were performed in the IORT group. IORT is not detrimental to subsequent
      radiological follow up.

PMID- 24332582
TI  - The value of electrochemotherapy in the treatment of peristomal tumors.
AB  - Electrochemotherapy (ECT) holds promise as a minimally invasive palliative tool
      for selected patients with peristomal tumors. We present the favorable short-term
      outcome of three patients (two with head and neck cancer, one with gastric
      cancer) successfully palliated by ECT. Treatment effectiveness and clinical
      benefit for patients with unresectable stoma recurrence need to be confirmed in
      future multicenter studies. 

PMID- 24332583
TI  - Endothelial progenitors.
AB  - The studies carried out during the last two decades have represented a great
      effort in trying to identify and define cell populations endowed with the
      phenotypic and functional properties of endothelial progenitors. From these
      studies a scenario now emerges indicating that in the blood there are very rare
      endothelial progenitor cells, called endothelial colony-forming cells (ECFCs) or
      late outgrowth endothelial cells, not originated from bone marrow, capable of
      generating phenotypically and functionally competent endothelial cells, capable
      to be incorporated in vivo into growing vessels. ECFCs are present in the
      circulation as well as cells resident in the vascular endothelial intima. In
      addition to these progenitors, there are some hematopoietic progenitor cells
      capable of generating a monocytic cell progeny exerting a pro-angiogenic activity
      in vivo, but unable to be directly incorporated into growing vessels. These cells
      exert a pro-angiogenic effect in vivo through a paracrine mechanism based on the
      secretion of growth factors and cytokines. 

PMID- 24332584
TI  - Temporomandibular joint replacement: a New Zealand perspective.
AB  - Alloplastic total temporomandibular joint replacement (TMJ TJR) has been
      performed in New Zealand utilizing the TMJ Concepts patient-fitted system since
      2000. The data analysed in this study were collected retrospectively from
      questionnaires sent to all maxillofacial surgeons in New Zealand who had
      implanted TMJ Concepts devices between 2000 and 2011. A total of 63 devices were
      implanted in 42 patients (13 males, 29 females) during this 12-year period. The
      primary indication for TMJ TJR was end-stage joint disease resulting from
      ankylosis and arthritis. The mean age of the patients was 47 years (range 7-80
      years). The most common complication reported was transient facial nerve
      impairment in 4.8% of the patients. Objective results, measured as the maximal
      incisional opening, improved by a mean of 17.3mm (P<0.01); 90% of patients
      reported improved quality of life. New Zealand oral and maxillofacial surgeons
      have concluded that TMJ TJR using the TMJ Concepts prosthesis is a reliable
      treatment option for the management of end-stage TMJ disease.

PMID- 24332585
TI  - Does computer-aided surgical simulation improve efficiency in bimaxillary
      orthognathic surgery?
AB  - The purpose of this study was to compare the efficiency of bimaxillary
      orthognathic surgery using computer-aided surgical simulation (CASS), with cases
      planned using traditional methods. Total doctor time was used to measure
      efficiency. While costs vary widely in different localities and in different
      health schemes, time is a valuable and limited resource everywhere. For this
      reason, total doctor time is a more useful measure of efficiency than is cost.
      Even though we use CASS primarily for planning more complex cases at the present
      time, this study showed an average saving of 60min for each case. In the context
      of a department that performs 200 bimaxillary cases each year, this would
      represent a saving of 25 days of doctor time, if applied to every case. It is
      concluded that CASS offers great potential for improving efficiency when used in
      the planning of bimaxillary orthognathic surgery. It saves significant doctor
      time that can be applied to additional surgical work.

PMID- 24332586
TI  - Effects of exercise on swallowing and tongue strength in patients with oral and
      oropharyngeal cancer treated with primary radiotherapy with or without
      chemotherapy.
AB  - Tongue strength is reduced in patients treated with chemoradiotherapy for
      oral/oropharyngeal cancer. Tongue strengthening protocols have resulted in
      improved lingual strength and swallowing in healthy individuals, as well as in
      patients following a neurological event. However, no studies have examined the
      efficacy of tongue strengthening exercises on tongue strength, swallowing, and
      quality of life (QOL; Head and Neck Cancer Inventory) in patients treated with
      chemoradiotherapy. A randomized clinical trial examined the effects of a tongue
      strengthening programme paired with traditional exercises vs. traditional
      exercises alone. Dependent variables included tongue strength, swallowing, and
      QOL in a group of patients with oral and oropharyngeal cancer treated with
      primary radiotherapy with or without chemotherapy. Differences with regard to
      tongue strength and oropharyngeal swallow efficiency (OPSE) were not observed
      within or between groups. QOL in the eating and speech domains improved following
      treatment in both groups. However, the experimental group demonstrated greater
      impairment in QOL in the social disruption domain following treatment, whereas
      the control group demonstrated a slight improvement in functioning. Tongue
      strengthening did not yield a statistically significant improvement in either
      tongue strength or swallowing measures in this patient cohort. Patient compliance
      and treatment timing may be factors underlying these outcomes.

PMID- 24332587
TI  - Effect of the route of administration of methylprednisolone on oedema and trismus
      in impacted lower third molar surgery.
AB  - Due to their anatomical position, the surgical removal of impacted third molars
      results in oedema, pain, and trismus. The purpose of this study was to evaluate
      the efficacy of supraperiosteal injection of methylprednisolone compared with an
      oral tablet form and intravenous (i.v.) injection in the prevention of
      postoperative pain and oedema associated with inflammation. This randomized,
      prospective, and controlled study included 44 patients. The patients were
      randomly divided into four groups: group 1 (control; no steroids), group 2 (local
      injection), group 3 (oral tablets), and group 4 (i.v. injection). On days 2 and 7
      following surgery, linear oedema was determined using facial landmarks, and
      maximal mouth opening was measured. Postoperative mouth opening and swelling were
      evaluated for each route of methylprednisolone administration and compared. The
      female (59%) to male (41%) ratio was 1.44; the mean age of the patients was 29.6
      years. The level of significance was set at P<0.01 for mouth opening and P<0.05
      for oedema. With regard to trismus, all three routes of administration
      demonstrated better efficacy in comparison to the control. While oral
      administration and i.v. injection of methylprednisolone achieved similar results,
      masseter injection provided better results in reducing oedema and trismus when
      compared to the control following lower third molar surgery.

PMID- 24332588
TI  - Effects of ozone therapy on pain, swelling, and trismus following third molar
      surgery.
AB  - The aim of this study was to evaluate the efficacy of therapeutic ozone
      application in the management of pain, swelling, and trismus associated with the
      surgical removal of impacted mandibular third molars. Sixty consecutive patients
      with asymptomatic bilateral impacted mandibular third molars were recruited into
      the study. Randomly, by use of envelops, the molar on one side was extracted and
      ozone therapy was given (study side); the molar on the other side was extracted 2
      weeks later and sham ozone therapy was given (negative control side). The mean
      age of the 60 patients was 22.6+/-2.3 years (range 18-25 years). No differences
      were found between the two sides for mouth opening or swelling. The degree of
      pain and the number of analgesic tablets taken was significantly lower for the
      study side. This study showed ozone therapy to have a positive effect on OHIP-14
      questionnaire results.

PMID- 24332589
TI  - Mandibular reconstruction in the growing patient with unilateral craniofacial
      microsomia: a systematic review.
AB  - The purpose of this systematic review is to provide an overview of the surgical
      correction of the mandible in unilateral craniofacial microsomia (UCM) performed
      in the growing patient, and its long-term outcome and stability. The following
      databases were searched: PubMed, Embase, Cochrane, and Web of Science. Articles
      reporting prospective and retrospective studies of patients not older than 16
      years (N >= 4) who had undergone surgical correction of a craniofacial microsomia
      spectrum condition using grafts, osteotomies, distraction, or combinations of
      these, were reviewed. The period of follow-up was selected to be >=1 year. After
      inclusion, the articles were evaluated on short- and long-term outcomes, relapse,
      and any increase in asymmetry following treatment. Thirty of 1611 articles were
      included in the qualitative synthesis. Analysis of the surgical mandibular
      correction of UCM showed that the outcome is not so much treatment-dependent, but
      patient-dependent, i.e. deformity gradation-dependent. The type I-IIa Pruzansky
      Kaban patient had the best results with regard to minimal relapse and/or minimal
      increase in asymmetry. Single-stage correction of the asymmetry should be
      postponed until the permanent dentition stage. It can be concluded that in the
      treatment of the severely hypoplastic mandible, the patient will benefit from a
      multi-stage treatment protocol if indicated for functional or psychological
      problems.

PMID- 24332590
TI  - Clinicopathological features of myxopapillary ependymoma.
AB  - Myxopapillary ependymoma (MPE) is a rare and distinct variant of ependymoma with
      a tendency for local recurrence and metastasis. Its clinicopathological spectrum
      is heterogenous, underscoring the need to understand and characterize MPE for
      better diagnosis and treatment. The purpose of this study was to explore the
      tumor biology and assess the management of patients with MPE. Tumors from a
      cohort of 19 patients were analyzed by light microscopy, electron microscopy,
      immunohistochemistry and fluorescence in situ hybridization (FISH). Clinical
      characteristics, therapeutic options and clinical follow-up data were also
      analyzed. Back pain was the most common presenting symptom. The main pathological
      morphology observed was papillae embedded in a myxoid background, but other rare
      morphologies were also present. Immunostaining revealed epidermal growth factor
      receptor (EGFR) expression in four MPE, while FISH for EGFR was negative. No
      correlation between tumor recurrence and EGFR overexpression was found.
      Ultrastructural examination revealed adherens junctions and intracytoplasmic
      lumina with microvilli. Patients with gross-total resection (GTR) had no tumor
      recurrence (p=0.021). Also, patients with subtotal resection (STR) followed by
      radiotherapy showed a higher local control rate than patients with STR alone
      (p=0.043). The diagnosis of MPE should be made considering the histology,
      immunohistochemistry, imaging studies and anatomical site. GTR of the tumor or
      STR followed by radiotherapy are more likely to avoid tumor recurrence than STR
      alone. Based on our findings, there is no correlation between tumor recurrence
      and EGFR expression. 

PMID- 24332592
TI  - Pathogenic memory type Th2 cells in allergic inflammation.
AB  - Immunological memory is a hallmark of adaptive immunity. Memory CD4 T helper (Th)
      cells are central to acquired immunity, and vaccines for infectious diseases are
      developed based on this concept. However, memory Th cells also play a critical
      role in the pathogenesis of various chronic inflammatory diseases, including
      asthma. We refer to these populations as 'pathogenic memory Th cells.' Here, we
      review recent developments highlighting the functions and characteristics of
      several pathogenic memory type Th2 cell subsets in allergic inflammation. Also
      discussed are the similarities and differences between pathogenic memory Th2
      cells and recently identified type 2 innate lymphoid cells (ILC2), focusing on
      cytokine production and phenotypic profiles. 

PMID- 24332591
TI  - BACH2-BCL6 balance regulates selection at the pre-B cell receptor checkpoint.
AB  - At the pre-B cell receptor (BCR) checkpoint, developing pre-B cells are selected
      for successful rearrangement of V(H)-DJ(H) gene segments and expression of a pre
      BCR. Reduced stringency at this checkpoint may obstruct the B cell repertoire
      with nonfunctional B cell clones. Earlier studies have described that activation
      of B cell lymphoma/leukemia (BCL)6 by a functional pre-BCR mediates positive
      selection of pre-B cells that have passed the checkpoint. This concept is now
      further elaborated by the recent finding that the BTB and CNC homology 1 basic
      leucine zipper transcription factor 2 (BACH2) induces negative selection and
      opposes BCL6 function prior to the pre-BCR checkpoint. Here, we discuss the
      antagonism between BCL6 and BACH2 during early B cell development, as well as its
      implications in both repertoire selection and counter-selection of premalignant
      clones for leukemia suppression.

PMID- 24332593
TI  - Significance of acute multiple infarcts in multiple cerebral circulations on
      initial diffusion weighted imaging in stroke patients.
AB  - OBJECTIVES: We attempted to assess the frequency, clinical and neuroradiological
      features of concomitant Acute Multiple Infarcts in Multiple Cerebral Circulations
      (AMIMCC) and to classify their causes. SUBJECTS AND METHODS: Consecutive patients
      treated for MR DWI-confirmed infarcts were included in this cohort. We
      retrospectively analyzed all patients with AMIMCC of our prospective database,
      studying clinical and radiological features. Causes of stroke were classified
      using TOAST and ASCO system (atherosclerosis, small vessel disease, cardiac
      source, other causes). RESULTS: Eighty AMIMCC were identified out of 824
      consecutive patients with MR DWI-confirmed infarcts (9.7%). Compared with single
      infarct patients, AMIMCC patients presented similar age and risk factors. Only 24
      AMIMCC patients (30%) presented symptoms suggesting multiple lesions before MRI.
      Cardiac origin existed in 39 of 80 patients (49%) including atrial fibrillation
      in 25 patients. Other sources of AMIMCC were hematologic diseases or
      coagulopathies such as intravascular coagulation in relation with cancer (n = 6;
      7,5%) and vasculitis or systemic disorders (n = 5;6,5%). AMIMCC also appeared to
      originate from unilateral carotid diseases or intracranial stenosis, mostly
      atheromatous, in association with anatomic variations(n = 9;11%). In 21 patients,
      no cause was identified despite extensive investigations (26%). According to
      TOAST classification, 62% had a definite source for infarcts, 67% according to
      ASCO grade 1 classification. MRI data did not permit to orientate etiological
      explorations according to DWI appearance, associated leucoaraiosis or previous
      infarcts on FLAIR or microbleeding on gradient-echo sequences. CONCLUSIONS:
      AMIMCC are not rare and mostly need MRI to be detected. Multiple and various
      etiologies are implicated, including cardioembolic diseases in half of them, but
      also hematologic disorders and angeitis.

PMID- 24332594
TI  - A model of acute compressive spinal cord injury with a minimally invasive balloon
      in goats.
AB  - Research into spinal cord injury depends upon animal models of trauma. While
      investigations using small animals have yielded critical insights into the
      cellular mechanisms of neurotrauma, no effective therapies have been translated
      to human clinical treatments. There are considerable differences in
      pathophysiology, scale, and anatomical organization between rodents and primates.
      Here, the established method of inflating balloons to compress the cord within
      the spinal canal was adapted for use in goats. By using surgical techniques to
      insert a kyphoplasty balloon, spinal cord injury was accomplished with minimal
      trauma to the surrounding tissues, as is common in other traumatic models. Dye
      volumes of 0, 1.26 +/- 0.18, and 2.82 +/- 0.20 mL were injected into the balloon
      to produce spinal occupancies of 0%, 33 +/- 2%, and 89 +/- 4%, as evaluated by X
      ray and computerized tomography imaging. A significant dose response was observed
      for the different levels of trauma, with reduced conduction of somatosensory
      evoked potentials and impaired mobility 7 days after injury. From the strong
      correlations between injection volume, balloon pressure, spinal occupancy, nerve
      function, and animal behavior, we conclude that hydraulic compression in goats is
      a useful model of spinal cord injury.

PMID- 24332595
TI  - Low serum 25-hydroxyvitamin D level: an independent risk factor for tuberculosis?
AB  - BACKGROUND & AIMS: Vitamin D deficiency has been associated with an increased
      risk of tuberculosis (TB). Low serum vitamin D levels may also be associated with
      poor nutritional status in TB patients. Therefore, this study aimed at evaluating
      the association between low serum vitamin D level and TB, regardless of other
      nutritional factors. METHODS: Baseline serum 25-hydroxyvitamin D (25(OH)D3)
      levels in TB patients were measured before treatment and 1 year after treatment
      onset using liquid chromatography-tandem mass spectrometry, and were compared
      with 25(OH)D3 levels in controls. Nutritional parameters were also measured in
      all subjects. RESULTS: In total, 165 active pulmonary TB patients and 197
      controls were included in the study. Significantly higher prevalence of 25(OH)D3
      insufficiency (<20 ng/mL) and deficiency (<10 ng/mL) in TB patients was showed
      compared to controls. Serum 25(OH)D3 levels and nutritional parameters were
      significantly lower in untreated TB patients than in controls. One year after TB
      treatment onset, nutritional parameters significantly increased; however, serum
      25(OH)D3 levels in TB patients showed no significant improvement compared to
      baseline. CONCLUSIONS: These results suggest that a low serum 25(OH)D3 level
      might be a risk factor for TB, independent of nutritional status.

PMID- 24332596
TI  - Does the size of the rod affect the surgical results in adolescent idiopathic
      scoliosis? 5.5-mm versus 6.35-mm rod.
AB  - BACKGROUND CONTEXT: Favorable clinical outcomes of surgical treatment with Cotrel
      Dubousset instrumentation (CDI) or instrumentations that follow the principles of
      CDI, for adolescent idiopathic scoliosis (AIS) have been reported. However, there
      are few studies concerning the results with rods of different sizes. PURPOSE: To
      find out whether the rod size affects the surgical results for AIS. STUDY DESIGN:
      A retrospective cohort study based on the same spinal system with different sizes
      of rod. PATIENT SAMPLE: A consecutive series of 93 patients, who underwent
      posterior correction with posterior instrumentation and fusion for AIS, were
      included and retrospectively analyzed. OUTCOME MEASURES: Postoperative radiologic
      outcomes were evaluated using coronal curves, percentage of curve correction, and
      coronal global balance. METHODS: Ninety-three patients treated during the period
      January 2000 to December 2008 were included in this study; 48 patients were
      treated with the Cotrel-Dubousset Horizon (CDH) M10 system with a 6.35-mm rod
      from January 2000 through December 2004, and a CDH M8 was used with a 5.5-mm rod
      in another 45 patients from January 2005 through December 2008. The Cobb angle,
      Risser grade, coronal curves, flexibility of curve, percentage of curve
      correction, coronal global balance, operative time, and estimated blood loss were
      measured and analyzed. The same parameters were used when the patient was
      followed at the OPD. All of the patients underwent regular follow-up for at least
      2 years. RESULTS: No statistical significance was observed in the demographic
      data, including age, sex, BMI, and Risser grade, between these 2 groups. The
      overall average percentage of correction was 60.0%+/-12.7%: 60.7%+/-12.5% for the
      CDH M10 group, and 59%+/-13.1% for the CDH M8 group. At the final follow-up, the
      overall average loss of correction was 4.8+/-3.9 degrees  for the CDH M10 group,
      and 4.3+/-4.0 degrees  for the CDH M8 group. The average percentage of correction
      at the final follow-up was 50.9%+/-15.1% for the CDH M10 group, and 51.1%+/-16.1%
      for the M8 group. No statistical significance could be observed in the radiologic
      parameters between these 2 groups. CONCLUSION: The radiologic results for the 5.5
      mm rod and the 6.35-mm rod were comparable in terms of correction, loss of
      correction, and coronal global balance.

PMID- 24332597
TI  - Association between body mass index, body height, and the prevalence of spinal
      deformities.
AB  - BACKGROUND CONTEXT: The most common spinal deformities among adolescents are
      adolescent idiopathic scoliosis (AIS; 2%-3% prevalence) and Scheuermann kyphosis
      (SK; 1%-8% prevalence). Both are believed to have a genetic influence in their
      etiology. The association between body mass index (BMI) and body stature and
      their possible association to spinal deformities is uncertain. STUDY DESIGN: A
      cross-sectional prevalence study. PURPOSE: To examine the prevalence of all
      adolescent spinal deformities according to the extent of their severity as well
      as their possible association to BMI and body height. OUTCOME MEASURES: Subjects
      diagnosed as having spinal deformities were classified into one of three severity
      groups; "Mild," "Intermediate," or "Severe," according to their curve scoliosis
      or kyphosis measurement with a standing X-ray. METHODS: The data for this study
      were derived from a medical database containing records of 17-year-old male and
      female patients before their recruitment into mandatory military service.
      Information on the disability codes associated with spinal deformities according
      to the Regulations of Medical Fitness Determination was retrieved. Logistic
      regression models were used to assess the association between the BMI and body
      height to various degrees of spinal deformities by severity. RESULTS: The study
      cohort included 829,791 consecutive subjects, of whom 103,249 were diagnosed with
      spinal deformities (76% were mild in degree). The prevalence of spinal
      deformities was significantly greater among the underweight male and female
      patients (p<.001). Increased BMI had a protective effect for developing spinal
      deformities. The odds ratios for severe spinal deformities were greater compared
      with mild spinal deformities in the underweight groups. The risk for developing
      spinal deformities increased significantly with height for both genders (p<.001).
      CONCLUSIONS: An association between height and the risk for spinal deformities by
      severity was found for all height groups. Below normal BMI is associated with
      severity of spinal deformities, whereas above-normal BMI apparently has a
      protective effect. Body height is also positively associated with the severity of
      spinal deformities.

PMID- 24332600
TI  - "Fere libenter homines id quod volunt credunt": apprehension for the stroke
      reduction in the KYOTO HEART Study on the basis of meta-regression from the
      evidence.

PMID- 24332599
TI  - Aortic biomechanics by magnetic resonance: early markers of aortic disease in
      Marfan syndrome regardless of aortic dilatation?
AB  - BACKGROUND: Previous studies demonstrated the usefulness of MRI in the evaluation
      of aortic biomechanics in Marfan patients with aortic dilatation. However, these
      parameters have not been well studied in earlier stages of aortic disease. The
      present work aimed to study aortic biomechanics: aortic distensibility (AD) and
      pulse wave velocity (PWV), by MRI in Marfan patients without advanced aortic
      disease. METHODS: Eighty consecutive Marfan patients were compared with 36 age-
      and sex-matched controls. MRI images at the level of ascending, descending and
      abdominal aorta were used to determine AD and PWV. RESULTS: Marfan patients (27
      men; age: 32.0 +/- 10.5 years; mean aortic root diameter: 37.2 +/- 4.6mm) had
      lower AD at all levels (ascending 2.6 +/- 2.1 vs. 6.2 +/- 3.7 mm Hg(-1).10(-3),
      p<0.001; descending 3.1 +/- 2.0 vs. 8.3 +/- 4.2, p<0.001; and abdominal 4.5 +/-
      2.2 vs. 14.0 +/- 5.2, p<0.001), higher aortic arch PWV (8.1 +/- 6.5 vs. 4.3 +/-
      1.8m/s, p<0.01) and ascending-to-abdominal PWV (6.1 +/- 3.0 vs. 4.7 +/- 1.5m/s,
      p<0.01) compared with controls. Thirty-five Marfan patients had a non-dilated
      aortic root (mean aortic root diameter: 34.5 +/- 3.8 mm). In multivariable
      analyses, after adjustment for age, pulse pressure and aortic dimensions, AD
      remained lower and PWV higher in Marfan patients; even Marfan patients with non
      dilated aortic root showed impaired aortic biomechanics compared with controls. Z
      score for ascending AD<-3.5 distinguished Marfan patients from controls with
      82.5% sensitivity and 86.1% specificity. CONCLUSIONS: Aortic biomechanics by MRI
      were abnormal in the entire aorta in Marfan patients. Moreover, Marfan patients
      without dilated aortic root showed clear impairment of aortic biomechanics, which
      suggests that they may be used as early markers of aortic involvement in these
      patients.

PMID- 24332598
TI  - Cardiac resynchronization therapy and AV optimization increase myocardial oxygen
      consumption, but increase cardiac function more than proportionally.
AB  - BACKGROUND: The mechanoenergetic effects of atrioventricular delay optimization
      during biventricular pacing ("cardiac resynchronization therapy", CRT) are
      unknown. METHODS: Eleven patients with heart failure and left bundle branch block
      (LBBB) underwent invasive measurements of left ventricular (LV) developed
      pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen
      consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD
      40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre
      identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction
      (LBBB). RESULTS: AV-120, relative to LBBB, increased LV developed pressure by a
      mean of 11(SEM 2)%, p=0.001, and aortic VTI by 11(SEM 3)%, p=0.002, but also
      increased MVO2 by 11(SEM 5)%, p=0.04. AV-Opt further increased LV developed
      pressure by a mean of 2(SEM 1)%, p=0.035 and aortic VTI by 4(SEM 1)%, p=0.017.
      MVO2 trended further up by 7(SEM 5)%, p=0.22. Mechanoenergetics at AV-40 were no
      different from LBBB. The 4 states lay on a straight line for Deltaexternal work
      (DeltaLV developed pressure * Deltaaortic VTI) against DeltaMVO2, with slope
      1.80, significantly >1 (p=0.02). CONCLUSIONS: Biventricular pacing and
      atrioventricular delay optimization increased external cardiac work done but also
      myocardial oxygen consumption. Nevertheless, the increase in cardiac work was
      ~80% greater than the increase in oxygen consumption, signifying an improvement
      in cardiac mechanoenergetics. Finally, the incremental effect of optimization on
      external work was approximately one-third beyond that of nominal AV pacing, along
      the same favourable efficiency trajectory, suggesting that AV delay dominates the
      biventricular pacing effect - which may therefore not be mainly
      "resynchronization".

PMID- 24332602
TI  - On the utility of quantitative diffusion-weighted MR imaging as a tool in
      differentiation between malignant and benign thyroid nodules.
AB  - RATIONALE AND OBJECTIVES: To evaluate the ability of diffusion-weighted magnetic
      resonance imaging (DWI) in differentiating malignant thyroid nodules from benign
      lesions with a meta-analysis. MATERIALS AND METHODS: Articles in English and
      Chinese language relating to the accuracy of DWI for this utility were retrieved.
      Pooled estimation and subgroup analysis data were obtained by statistical
      analysis. RESULTS: A total of seven studies (17 subsets) with 358 patients, who
      fulfilled all of the inclusion criteria, were considered for the analysis. No
      publication bias was found (bias = 7.03, P > .05). Methodological quality was
      relatively high. DWI sensitivity was 0.91 (95% confidence interval [CI], 0.87
      0.94) and specificity was 0.93 (95% CI, 0.86-0.96). Overall, positive likelihood
      ratio was 12.24 (95% CI, 6.47-23.20) and negative likelihood ratio was 0.99 (95%
      CI, 0.06-0.15). Diagnostic odds ratio was 123.78 (95% CI, 56.85-269.48). The area
      under the curve of the summary receiver operating characteristic was 0.94 (95%
      CI, 0.92-0.96). In patients with high pretest probabilities, DWI enabled
      confirmation of malignant thyroid lesion; in patients with low pretest
      probabilities, DWI enabled exclusion of malignant thyroid lesion. Worst-case
      scenario (pretest probability, 50%) posttest probabilities were 92% and 9% for
      positive and negative DWI results, respectively. CONCLUSIONS: A limited number of
      small studies suggests that quantitative DWI is a reliable diagnostic method for
      differentiation between benign and malignant thyroid lesions.

PMID- 24332601
TI  - Langerhans cell histiocytosis of the urinary bladder in a patient with bladder
      cancer previously treated with intravesical Bacillus Calmette-Guerin therapy.
AB  - We report an extremely rare case of Langerhans cell histiocytosis (LCH) of the
      urinary bladder. A 68-year-old man presented with gross hematuria. Cystoscopy
      showed multiple papillary tumors in the urinary bladder, and transurethral
      resection was performed. Pathological diagnosis was high-grade papillary
      urothelial carcinoma with lamina propria invasion. The patient received six
      treatments with intravesical Bacillus Calmette-Guerin (BCG) therapy. Seven months
      after surgery, follow-up cystoscopy showed three elevated lesions in the urinary
      bladder, two of which were identified histologically as recurrent urothelial
      carcinoma. Microscopic examination of the lesion at the anterior wall revealed
      diffuse infiltration of medium to large histiocytoid cells in the lamina propria,
      many of which had distorted nuclei and nuclear grooves. Dense eosinophilic
      infiltration was also observed. Immunohistochemically, the histiocytoid cells
      were diffusely positive for S-100 and CD1a, but negative for cytokeratin AE1/AE3
      and melanosome-associated antigen recognized by HMB-45. Based on the histological
      and immunohistochemical features, we diagnosed the lesion as LCH of the urinary
      bladder. There was no evidence of recurrence of either bladder cancer or LCH
      after an 18-month follow-up. To avoid misdiagnosis, urologists and pathologists
      should be aware that LCH may develop in the urinary bladder after intravesical
      BCG therapy for bladder cancer. 

PMID- 24332603
TI  - Impact of a new motion-correction algorithm on image quality of low-dose coronary
      CT angiography in patients with insufficient heart rate control.
AB  - RATIONALE AND OBJECTIVES: Prospective electrocardiogram (ECG) triggering allows
      coronary computed tomography angiography (CCTA) scanning with low radiation dose
      but requires heart rates below 63 beats/min. We assessed the impact of a novel
      vendor-specific motion-correction algorithm on image quality and interpretability
      of low-dose CCTA acquired despite insufficient heart rate control. MATERIALS AND
      METHODS: In 40 patients undergoing CCTA for the assessment of known or suspected
      coronary artery disease who did not reach the target heart rate below 63
      beats/min despite beta-blockade before prospective low-dose scanning, the
      temporal acquisition window was increased (80 ms additional padding). The new
      algorithm detects and integrates vessel path and velocity from adjacent cardiac
      phases for motion correction. Two blinded observers assessed image quality on a 4
      point Likert scale (1, nonevaluative; 2, reduced but evaluative; 3, good; and 4,
      excellent) and the fraction of interpretable segments (score 2 or more) using
      motion correction versus standard reconstruction. RESULTS: Image reconstruction
      with motion correction resulted in an increased median coronary artery image
      quality score (excellent interobserver agreement, kappa = 0.85) compared to
      standard reconstruction (3.4 vs. 3.0, P < .001). Consequently, motion-corrected
      reconstruction significantly improved the overall interpretability of coronary
      arteries (from 78% to 88%, P < .001). Estimated mean effective radiation dose was
      2.3 +/- 0.8 mSv. CONCLUSIONS: A novel, vendor-specific, motion-corrected,
      reconstruction algorithm improves image quality and interpretability of
      prospectively ECG-triggered low-dose CCTA despite insufficient heart rate
      control.

PMID- 24332604
TI  - International Atherosclerosis Society position paper: global recommendations for
      the management of dyslipidemia.

PMID- 24332605
TI  - Recovery pattern of non-protein respiratory quotient and non-esterified fatty
      acids after liver resection.
AB  - OBJECTIVE: Perioperative nutritional care is important to maintain preoperative
      and postoperative nutritional status. However, few reports have investigated
      energy metabolism after hepatectomy. The aim of this study was to determine
      differences in energy metabolism, blood biochemistry, and nutritional status
      before and after liver resection in patients with hepatocellular carcinoma (HCC)
      and healthy living donors for liver transplantation. METHODS: Eighteen
      hospitalized patients with HCC group and 13 living donors for liver
      transplantation (donor group) were enrolled in this study. The donor group was
      divided into two groups on the basis of age; Y-donor group (age < 40 y, n = 7),
      and O-donor group (age >= 40 y, n = 6). Energy metabolism was measured by
      indirect calorimetry at preoperative day and postoperative day (POD) 7 and 14,
      and blood biochemistry was also examined. RESULTS: Recovery of non-protein
      respiratory quotient (npRQ) and blood biochemical data such as total bilirubin,
      aspartate aminotransferase and alanine aminotransferase levels were observed in Y
      donor group on POD 14. However, although biochemical data improved in the HCC and
      O-donor group, npRQ remained unchanged on POD 14. CONCLUSIONS: Improvement of
      npRQ took longer than blood biochemical data in patients with HCC and older
      donors. Because the recovery of npRQ is associated with donor age, careful
      nutritional management may be required for a longer time depending on the
      pathophysiological condition of each patient after hepatectomy.

PMID- 24332606
TI  - Epigenetic regulation of the ABCB1 gene in drug-sensitive and drug-resistant
      lymphoid tumour cell lines obtained from canine patients.
AB  - Multidrug resistance (MDR) is a major obstacle in the treatment of cancer.
      Overexpression of P-glycoprotein (P-gp), encoded by the ABCB1 (MDR1) gene, is an
      important factor in determining the MDR phenotype of a tumour. Although recent
      studies have revealed the epigenetic transcriptional regulation of the human
      ABCB1 gene, such regulation of this gene has not been examined in dogs. The aim
      of the current study was to evaluate differences in epigenetic regulation of the
      ABCB1 gene, between drug-sensitive and drug-resistant canine lymphoid tumour cell
      lines. In two drug-sensitive cell lines, GL-1 and CLBL-1, ABCB1 mRNA expression
      was significantly lower than in two drug-resistant cell lines, UL-1 and Ema,
      using real-time quantitative polymerase chain reaction (QPCR). Bisulphite
      sequencing and real-time methylation-specific PCR revealed that the CpG island
      present in the upstream region of exon 2 was hypermethylated in GL-1 and CLBL-1,
      but hypomethylated in UL-1 and Ema. Chromatin immunoprecipitation and QPCR
      revealed that histone H3 acetylation in the same CpG island was significantly
      increased in UL-1 and Ema compared to GL-1 and CLBL-1. Treatment with 5-aza 2'
      deoxycytidine or trichostatin A increased ABCB1 mRNA expression in GL-1 and CLBL
      1. DNA methylation and histone H3 acetylation were shown to be involved in ABCB1
      gene expression and associated with an MDR phenotype in these canine lymphoid
      tumour cell lines. 

PMID- 24332607
TI  - Long term quality of life in pediatric patients surviving parotid tumors.
AB  - OBJECTIVE: To evaluate the long term quality of life in pediatric patients who
      have survived parotid tumors. METHODS: A quality of life instrument, based on the
      principles of the University of Washington Quality of Life questionnaire, was
      specifically created for this study and sent to pediatric patients who had
      undergone a parotidectomy between 2000 and 2008. RESULTS: The mean general health
      score was 3.45, which was deemed good to very good. The highest overall score in
      the group was 99.24. These results indicated that almost no patients complained
      of pain. Initially, 10 patients had reported that sensation was affected, but six
      of these cases recovered. Three (9.1%) patients reported a change in their
      appearance. Two patients (6.1%) reported surgical site depression and a further
      two (6.1%) reported scarring depression. Six (18.2%) patients reported facial
      nerve impairment during the early postoperative period, and four of these cases
      recovered. Two patients reported fistula during the early postoperative period,
      and but the symptoms were resolved after intervention. Frey's syndrome was
      reported by three (9.1%) patients. CONCLUSION: Parotidectomy has a limited
      negative impact on pediatric patients' quality of life.

PMID- 24332608
TI  - Castleman's Disease: a rare finding in a pediatric neck.
AB  - Castleman's Disease is a rare lymphoproliferative disorder. In the literature,
      only 29 cases, associated with the neck presentation in children, have been
      reported. This is another case report regarding a 5-year old child who presented
      with a persistent cervical lymphadenopathy. Final pathology, after undergoing
      exploratory neck dissection and surgical excision, revealed Castleman's Disease.
      This report, augmented with a literature review of all the 29 cases, compares the
      clinical course of this patient with the other cases. In conclusion, although
      Castleman's Disease carries a favorable prognosis in children, surgical excision
      is recommended to confirm the diagnosis and to rule out other causes. 

PMID- 24332609
TI  - Establishing auditory steady-state response thresholds to narrow band CE
      chirps((r)) in full-term neonates.
AB  - Narrow band CE-chirps((r)) were developed to provide a better synchronization of
      neural response due to the compensation of the traveling wave delay in the
      basilar membrane. These stimuli combined with a detection method that includes
      higher response harmonics on the auditory steady-state response (ASSR) recording
      was studied in this research. OBJECTIVE: (1) To establish air conduction
      thresholds for ASSR to narrow band CE-chirp((r)) in normal hearing full-term
      neonates; (2) describe the test time needed for the above in one ear and (3) to
      compare the results in infants and normally hearing adults. METHOD: ASSR to air
      conducted stimuli were obtained in 30 full-term neonates (14 girls and 16 boys)
      with an average age of 34.3h of life. All neonates were presented presence of
      transient-evoked otoacoustic emissions (TEOAE) and result "pass" in automatic ABR
      at 35dB nHL before ASSR test. ASSR thresholds of both ears of 10 normal hearing
      adults (5 girls and 5 boys) varied in age between 23 and 30 years and with
      hearing thresholds better than or equal to 15dB HL at all frequencies between 250
      and 8000Hz were recorded to compare with the neonate data. RESULTS: The neonate
      ASSR thresholds estimated from 50% using cumulative distributions were 24.5,
      13.5, 7.5 and 10dB nHL at 500, 1000, 2000, and 4000Hz, respectively. For the same
      frequency order, ASSR thresholds estimated from 90% of the neonates were 34.5,
      28, 12.5 and 15dB nHL. It required 21.2 (+/-5)min on average to obtain threshold
      in each ear in neonates, with a range of 12-29min. When ASSR thresholds recorded
      in full-term neonates and adults were directly compared, the differences between
      these groups were not significant for 1000Hz (p=0.500), 2000Hz (p=0.610) and
      4000Hz (p=0.362). However, at 500Hz, ASSR thresholds in neonates tend to be
      greater than in adults (p=0.001). CONCLUSION: In this study ASSR thresholds
      estimated from 90% of the neonates were 34.5, 28, 12.5 and 15dB nHL. It required
      21.2 (+/-5)min on average to obtain threshold in each ear and ASSR thresholds to
      narrow band CE-chirp((r)) in neonates are not significant for adults ASSR
      thresholds, except at 500Hz, when the ASSR thresholds in neonates tend to be
      greater than in adults.

PMID- 24332610
TI  - The risk factor profile of children covered by the Polish universal neonatal
      hearing screening program and its impact on hearing loss incidence.
AB  - OBJECTIVE: The high frequency of risk factors detected within the newborn
      population increases the total number of children that should receive regular
      follow-ups. However, in some circumstances, this could be beyond the capacity of
      the health system. Therefore, careful interpretation and selection of risk
      factors, and in particular of those factors not strictly defined, should be
      carried out during screening. The aim of the study was to analyse the risk factor
      profile of children covered by the national universal neonatal hearing screening
      program and to correlate it with hearing loss incidence. PATIENTS AND METHODS:
      The analysis of records in the program database collected from 472 neonatal and
      well-baby units over a period of 10 years (2002-2012), focused on children with
      at least one risk factor. The analysis was subdivided into distribution of risk
      factors as well as to risk factors and hearing loss correlation. RESULTS: In the
      studied cohort of n=137,432 children (4% of the total number of screened
      children) single risk factors were most frequently detected, accounting for 71%
      of records. The association of two or more risk factors appeared in 659
      configurations (29%), with a mean of 3.1 coexisting risk factors and a maximum of
      9. Hearing loss was dependent on the number of risk factors in a child, but
      reached its maximum with the association of 6 factors. CONCLUSIONS: The detection
      of postnatal hearing loss should be continued in order to increase our
      understanding of hearing incidence and the role of environmental factors. To
      optimize screening, discussions between specialists (mostly related to the issue
      of risk factors detected and registered in the earliest stage of screening
      programs) would be beneficial.

PMID- 24332611
TI  - The journal continues to evolve.

PMID- 24332612
TI  - Virilized external genitalia in young girls: clinical characteristics and
      management challenges in a low-resource setting.
AB  - OBJECTIVE: Virilization of the external genitalia in young girls (VEG) manifests
      mostly as ambiguity of the genitalia and elicits concerns and uncertainties
      especially in settings with poor awareness. This study evaluates the profile and
      challenges of VEG in southeast Nigeria. METHODS: We analyzed 23 children with VEG
      managed in 2 referral centers in southeast Nigeria from June 2005 to January
      2013. RESULTS: They presented at median age of 13.3 months (interquartile range
      [IQR] 3 months-3 years). The cases included 3 (13%) of Prader type 1, 6 (26%) of
      type 2, 11 (48%) of type 3, and 3 (13%) of type 4. Five of the Prader type 3 and
      all 3 cases of Prader type 4 were reared as male prior to presentation. Following
      evaluation, all the cases were assigned female gender at a mean age of 2.7 years
      (range 2 months-10.5 years). Appropriate feminizing genitoplasty was undertaken
      in all the cases and after a follow-up period of 3 months to 5 years (mean 2
      years), 2 patients developed vaginal stenosis, and 3 cases had surgical wound
      infection. Poor awareness, delayed presentation, inadequate facilities, and lack
      of trained manpower were the challenges in the management of the cases.
      CONCLUSION: VEG in our setting is associated with delayed management. Focused
      health education and public awareness programs, and improved healthcare funding
      may improve outcome and minimize the need for gender reassignment.

PMID- 24332613
TI  - Use of digital media technology for primary prevention of STIs/HIV in youth.
AB  - STUDY OBJECTIVE: The relevant literature was reviewed to identify issues in
      research evaluating digital media technology (DMT) interventions for the primary
      prevention of STIs/HIV in adolescents and young adults. METHOD: A literature
      search with relevant key terms was conducted in PubMed, for articles with studies
      that included: (a) participants between 11-29 years; (b) use of one or more of
      the following forms of DMT: interactive digital video or CD-ROM, computer, text
      messaging, or Internet; (c) evaluation of an STI/HIV primary prevention
      intervention; and (d) use of a cognitive, psychosocial, behavioral, or biological
      outcome. RESULTS: Twenty-nine studies were identified and included in the review.
      Based on the review of these studies, 7 main issues were discussed and
      recommendations for improving future research were offered. The 7 main issues
      were: (a) need for a balance between universal application and specific sub-group
      focus, (b) lack of a developmental framework, (c) challenge of applying DMT in
      resource limited contexts, (d) rapidly changing nature of DMT, (e) lack of
      biological outcomes, (f) lack of comparison/control groups to assess the impact
      of DMT, and (g) limited temporal follow-up. CONCLUSIONS: There is increasing
      literature evaluating the effectiveness of DMT for preventing STIs/HIV among
      adolescents and young adults. A careful consideration of 7 main issues identified
      in the literature can improve the design and evaluation of these interventions
      and enhance our understanding of their effectiveness.

PMID- 24332614
TI  - Torsion of fallopian tube remnant associated with noncommunicating rudimentary
      horn in adolescent girl with unicornuate uterus.
AB  - BACKGROUND: The prevalence of mullerian anomalies may be as high as 7% in the
      general population, yet there is scant published literature on adnexal torsion
      occurring in these patients. CASE: A 14-year-old female presented with right
      lower quadrant pain. Pelvic ultrasonography demonstrated a 2-cm simple right
      adnexal cyst. Diagnostic laparoscopy revealed a unicornuate uterus with a normal
      left uterine horn and fallopian tube but atretic and cordlike mullerian
      structures on the right side. Torsion of the right tubal remnant and two
      paratubal cysts were noted and the structures were then excised. SUMMARY AND
      CONCLUSION: Agenesis, hypoplasia, or maldevelopment of mullerian structures may
      predispose patients to an increased risk of adnexal torsion secondary to looser
      ligamentous attachments and consequent lack of fixation to the pelvic sidewall.

PMID- 24332615
TI  - The effect of perturbing body segment parameters on calculated joint moments and
      muscle forces during gait.
AB  - This study examined the effect of body segment parameter (BSP) perturbations on
      joint moments calculated using an inverse dynamics procedure and muscle forces
      calculated using computed muscle control (CMC) during gait. BSP (i.e. segment
      mass, center of mass location (com) and inertia tensor) of the left thigh, shank
      and foot of a scaled musculoskeletal model were perturbed. These perturbations
      started from their nominal value and were adjusted to +/-40% in steps of 10%, for
      both individual as well as combined perturbations in BSP. For all perturbations,
      an inverse dynamics procedure calculated the ankle, knee and hip moments based on
      an identical inverse kinematics solution. Furthermore, the effect of applying a
      residual reduction algorithm (RRA) was investigated. Muscle excitations and
      resulting muscle forces were calculated using CMC. The results show only a
      limited effect of an individual parameter perturbation on the calculated moments,
      where the largest effect is found when perturbing the shank com (MS(com,shank),
      the ratio of absolute difference in torque and relative parameter perturbation,
      is maximally -7.81 N m for hip flexion moment). The additional influence of
      perturbing two parameters simultaneously is small (MS(mass+com,thigh) is
      maximally 15.2 N m for hip flexion moment). RRA made small changes to the model
      to increase the dynamic consistency of the simulation (after RRA MS(com,shank) is
      maximally 5.01 N m). CMC results show large differences in muscle forces when BSP
      are perturbed. These result from the underlying forward integration of the
      dynamic equations.

PMID- 24332616
TI  - Tensile properties of the medial patellofemoral ligament: the effect of specimen
      orientation.
AB  - For recurrent patellar dislocation, reconstruction of the medial patellofemoral
      ligament (MPFL) with replacement autografts has often been performed but with
      only little data on the tensile properties of the MPFL to guide graft selection.
      With its complex anatomy and geometry, these properties are difficult to obtain.
      In this study, we showed how the orientation of the femur-MPFL-patella complex
      (FMPC) during uniaxial tensile testing can have a significant effect on its
      structural properties. Twenty two FMPCs were isolated from porcine stifle joints
      and randomly assigned to two groups of 11 each. For the first group, the
      specimens were loaded to failure with the patella oriented 30 degrees away from
      the direction of the applied load to mimic its orientation in situ, called
      natural orientation. In the second group, the patella was aligned in the
      direction of the tensile load, called non-natural orientation. The stiffness for
      the natural orientation group was 65+/-13 N/mm, 32% higher than that for the non
      natural orientation group (50+/-17 N/mm; p<0.05). The ultimate loads were 438+/
      128 N and 386+/-136 N, respectively (p>0.05). Ten out of 11 specimens in the
      natural orientation group failed at the femoral attachment (the narrowest portion
      of the MPFL) compared to 6 out of 11 in the non-natural orientation group. Our
      findings suggest that the specimen orientation that mimics the in-situ loading
      conditions of the MPFL should be used to obtain more representative data for the
      structural properties of the FMPC.

PMID- 24332617
TI  - Effect of glutaraldehyde fixation on the frictional response of immature bovine
      articular cartilage explants.
AB  - This study examined functional properties and biocompatibility of glutaraldehyde
      fixed bovine articular cartilage over several weeks of incubation at body
      temperature to investigate its potential use as a resurfacing material in joint
      arthroplasty. In the first experiment, treated cartilage disks were fixed using
      0.02, 0.20 and 0.60% glutaraldehyde for 24h then incubated, along with an
      untreated control group, in saline for up to 28d at 37 degrees C. Both the
      equilibrium compressive and tensile moduli increased nearly twofold in treated
      samples compared to day 0 control, and remained at that level from day 1 to 28;
      the equilibrium friction coefficient against glass rose nearly twofold
      immediately after fixation (day 1) but returned to control values after day 7.
      Live explants co-cultured with fixed explants showed no quantitative difference
      in cell viability over 28d. In general, no significant differences were observed
      between 0.20 and 0.60% groups, so 0.20% was deemed sufficient for complete
      fixation. In the second experiment, cartilage-on-cartilage frictional
      measurements were performed under a migrating contact configuration. In the
      treated group, one explant was fixed using 0.20% glutaraldehyde while the
      apposing explant was left untreated; in the control group both explants were left
      untreated. From day 1 to 28, the treated group exhibited either no significant
      difference or slightly lower friction coefficient than the untreated group. These
      results suggest that a properly titrated glutaraldehyde treatment can reproduce
      the desired functional properties of native articular cartilage and maintain
      these properties for at least 28d at body temperature. 

PMID- 24332618
TI  - Biomechanical adaptation of the bone-periodontal ligament (PDL)-tooth fibrous
      joint as a consequence of disease.
AB  - In this study, an in vivo ligature-induced periodontitis rat model was used to
      investigate temporal changes to the solid and fluid phases of the joint by
      correlating shifts in joint biomechanics to adaptive changes in soft and hard
      tissue morphology and functional space. After 6 and 12 weeks of ligation, coronal
      regions showed a significant decrease in alveolar crest height, increased
      expression of TNF-alpha, and degradation of attachment fibers as indicated by
      decreased collagen birefringence. Cyclical compression to peak loads of 5-15N at
      speeds of 0.2-2.0mm/min followed by load relaxation tests showed decreased
      stiffness and reactionary load rate values, load relaxation, and load
      recoverability, of ligated joints. Shifts in joint stiffness and reactionary load
      rate increased with time while shifts in joint relaxation and recoverability
      decreased between control and ligated groups, complementing measurements of
      increased tooth displacement as evaluated through digital image correlation.
      Shifts in functional space between control and ligated joints were significantly
      increased at the interradicular (Delta10-25MUm) and distal coronal (Delta20
      45MUm) regions. Histology revealed time-dependent increases in nuclei elongation
      within PDL cells and collagen fiber alignment, uncrimping, and directionality, in
      12-week ligated joints compared to random orientation in 6-week ligated joints
      and to controls. We propose that altered strains from tooth hypermobility could
      cause varying degrees of solid-to-fluid compaction, alter dampening
      characteristics of the joint, and potentiate increased adaptation at the risk of
      joint failure. 

PMID- 24332619
TI  - Recurrent anterior instability of the radial head: case report.
AB  - We present a case of recurrent anterior instability of the radial head presenting
      4 weeks after injury. A 16-year-old girl injured the right upper extremity while
      playing volleyball. Thereafter, she felt a recurrent click associated with pain
      in the elbow when rotating the forearm. Image intensifier findings implied that
      the radial head would anteriorly dislocate with contraction of the biceps
      brachii. Annular ligament reconstruction using the palmaris longus tendon graft
      relieved the instability. 

PMID- 24332620
TI  - Social disparities in women's health service use in the United States: a
      population-based analysis.
AB  - PURPOSE: Poor and disparate reproductive health outcomes in the United States may
      be related to inadequate and differential receipt of women's health care. We
      investigated trends in and determinants of adult U.S. women's health service use,
      2006-2010. METHODS: We analyzed population data from 7897 women aged 25-44 years
      in the National Survey of Family Growth from 2006 to 2010 using multivariable
      logistic regression. RESULTS: Women's health service use in the past year was
      reported by 74% of the sample. Among noninfertile, sexually active women, 47%
      used contraceptive services; fewer used pregnancy (21%) and sexually transmitted
      infection (14%) services. In multivariable models, the odds of service use were
      greater among older, poor, unemployed women and women with less educational
      attainment than younger and socioeconomically advantaged women. Black women had
      greater odds of using pregnancy, sexually transmitted infection and gynecologic
      examination services than white women (odds ratio, 1.4-1.6). Lack of insurance
      was associated with service use in all models (odds ratio, 0.4-0.8). CONCLUSIONS:
      Although age-related differences in women's health service use may reflect
      fertility transitions, social disparities mirror reproductive inequalities among
      U.S. women. Research on women's health service use and outcomes across the
      reproductive life course and forthcoming sociopolitical climates is needed.

PMID- 24332621
TI  - Mechanical properties of protein adsorption layers at the air/water and oil/water
      interface: a comparison in light of the thermodynamical stability of proteins.
AB  - Over the last decades numerous studies on the interfacial rheological response of
      protein adsorption layers have been published. The comparison of these studies
      and the retrieval of a common parameter to compare protein interfacial activity
      are hampered by the fact that different boundary conditions (e.g. physico
      chemical, instrumental, interfacial) were used. In the present work we review
      previous studies and attempt a unifying approach for the comparison between bulk
      protein properties and their adsorption films. Among many common food grade
      proteins we chose bovine serum albumin, beta-lactoglobulin and lysozyme for their
      difference in thermodynamic stability and studied their adsorption at the
      air/water and limonene/water interface. In order to achieve this we have i)
      systematically analyzed protein adsorption kinetics in terms of surface pressure
      rise using a drop profile analysis tensiometer and ii) we addressed the
      interfacial layer properties under shear stress using an interfacial shear
      rheometer under the same experimental conditions. We could show that
      thermodynamically less stable proteins adsorb generally faster and yield films
      with higher shear rheological properties at air/water interface. The same
      proteins showed an analog behavior when adsorbing at the limonene/water interface
      but at slower rates. 

PMID- 24332622
TI  - Antimicrobial polymer nanostructures: synthetic route, mechanism of action and
      perspective.
AB  - Protection against bacterial infections is an important research field in modern
      society. Antimicrobial polymers have received considerable attention as next
      generation biocides because they represent an ecologically friendly approach that
      does not promote resistance. In the last decade, many authors have reported the
      development of nano-sized antimicrobial polymers with enhanced bactericidal
      performance by increasing the active-area of biocides. This review presents
      several suitable methods of synthesis of antimicrobial polymer nanomaterials with
      various shapes, including a nanosphere and fibrous and tubular structures. We
      also discuss the antimicrobial mechanisms of these polymers. In addition,
      antimicrobial polymer thin films, which can inhibit bacterial adhesion, are
      introduced briefly with examples. Our aim is to present synthetic routes and
      formation mechanisms of various antimicrobial polymer nanostructures. 

PMID- 24332623
TI  - Synthesis of a novel series of artemisinin dimers with potent anticancer activity
      involving Sonogashira cross-coupling reaction.
AB  - A series of C-10 acetal artemisinin dimers were synthesized using Sonogashira
      cross-coupling reaction. All these novel semisynthetic artemisinin dimers
      exhibited excellent growth inhibitory activity against Lung A-549 human cancer
      cell line. 

PMID- 24332624
TI  - Replacement of amide with bioisosteres led to a new series of potent adenosine
      A2A receptor antagonists.
AB  - We have previously reported a series of 2,4,6-trisubstituted pyrimidines as
      potent A2A receptor antagonists. The leading compounds often feature a
      potentially labile acetamide functional group which tends to hydrolyze under
      acidic conditions. Here we report the replacement of the acetamide functional
      group with bioisosteres. This effort led us to a new series of adenosine A2A
      receptor antagonists with improved potency and chemical stability. 

PMID- 24332625
TI  - Synthesis and antimycobacterial activity of novel camphane-based agents.
AB  - A series of six new amidoalcohols was designed and synthesized on the base of the
      camphor scaffold. Natural amino acids were transformed into their alpha-hydroxy
      analogues with retention of configuration, and attached to isobornylamine. The
      compounds were evaluated for their in vitro activity against Mycobacterium
      tuberculosis H37Rv. Some of the new compounds show 25 times higher activity than
      the classical anti-TB drug ethambutol. The activity shifts from micromolar to
      nanomolar inhibitory concentrations depending on the alpha-hydroxy acid moiety.
      Two of the most potent compounds exert low level of cytotoxic activity. These
      camphane-based amido-alcohols present promising potential lead compounds for
      further elaboration of antimycobacterial agents. 

PMID- 24332626
TI  - New titanocene derivatives with high antiproliferative activity against breast
      cancer cells.
AB  - The synthesis and characterization of some new titanocene-complexes, having a
      ethenyl-phenoxide or a benzyl group as substituents of the cyclopentadienyl
      rings, are reported. The synthesized compounds have been evaluated for their
      cytotoxic potential against two human breast cancer cell lines, that is: MCF7 and
      SkBr3. Most of these compounds have shown significant cytotoxic effects, compared
      to cisplatin, in MTT-based cell tests. 

PMID- 24332627
TI  - Synthesis and biological evaluation of cyclopentyl-triazolol-pyrimidine (CPTP)
      based P2Y12 antagonists.
AB  - In this Letter we describe SAR investigation on the cyclopentyl-triazolol
      pyrimidine scaffold in pursuit of new oral P2Y12 inhibitors. Different synthetic
      routes were developed for variations at the cyclopentyl core. Optimization
      finally led to compound 2d which was advanced into preclinical development based
      on better potency and safety profile in comparison to ticagrelor. 

PMID- 24332628
TI  - Design, synthesis and antibacterial activities of 5-(pyrazin-2-yl)-4H-1,2,4
      triazole-3-thiol derivatives containing Schiff base formation as FabH inhibitory.
AB  - A series of novel schiff base derivatives (H(1)-H(20)) containing pyrazine and
      triazole moiety have been designed and synthesized, and their biological
      activities were also evaluated as potential inhibitors of beta-ketoacyl-acyl
      carrier protein synthase III (FabH). These compounds were assayed for
      antibacterial activity against Escherichia coli, Pseudomonas aeruginosa,
      Staphylococcus aureus, Bacillus subtilis and Bacillus amyloliquefaciens and
      selected compounds among them were tested for their Escherichia coli FabH
      inhibitory activity. Based on the biological data, compound H(17) showed the most
      potent antibacterial activity with MIC values of 0.39-1.56MUg/mL against the
      tested bacterial strains and exhibited the most potent E. coli FabH inhibitory
      activity with IC50 of 5.2MUM, being better than the positive control Kanamycin B
      with IC50 of 6.3MUM. Furthermore, docking simulation was performed to position
      compound H(17) into the E. coli FabH active site to determine the probable
      binding conformation. This study indicated that compound H(17) has demonstrated
      significant E. coli FabH inhibitory activity as a potential antibacterial agent
      and provides valuable information for the design of E. coli FabH inhibitors. 

PMID- 24332629
TI  - Verrulactone C with an unprecedented dispiro skeleton, a new inhibitor of
      Staphylococcus aureus enoyl-ACP reductase, from Penicillium verruculosum F375.
AB  - An highly quaternary and unprecedented dispiro compound, verrulactone C, with the
      known compound, altenuisol, were isolated from a culture broth of the fungal
      strain Penicillium verruculosum F375 and their structures were established by
      various spectral analysis. Verrulactone C and altenuisol showed FabI-selective
      inhibition. Especially altenuisol had the high correlation between FabI
      inhibition and whole cell antibacterial activity against Staphylococcus aureus
      and MRSA with MICs of 8-32MUg/mL. 

PMID- 24332630
TI  - Design and synthesis of tamoxifen derivatives as a selective estrogen receptor
      down-regulator.
AB  - We designed and synthesized an estrogen receptor (ER) down-regulator (5), which
      is a derivative of tamoxifen with a long alkyl side chain. Compound 5 effectively
      reduced ER protein levels in MCF-7 cells and had an antagonistic effect. 

PMID- 24332631
TI  - Cassaine diterpene alkaloids from Erythrophleum fordii and their anti-angiogenic
      effect.
AB  - Angiogenesis plays a critical role in embryonic development and various
      physiological processes. However, excessive angiogenesis is associated with
      several pathological conditions including cancer. Angiogenesis is closely related
      to tumor growth, invasion and metastasis, and is considered a prime target for
      anticancer therapy. In this study, two new mono cassaine diterpenoid amides (1,
      5) and four known compounds (2-4, 6) were isolated from the bark of Erythrophleum
      fordii (Leguminosae). Their chemical structures were established mainly by 1D and
      2D NMR techniques and mass spectrometry. The effects of isolates on endothelial
      tube formation on Matrigel were investigated. Among them, compound 3 was found to
      have the most potent inhibitory effect on the capillary-like structure formation
      of human umbilical vein endothelial cells (HUVECs). 

PMID- 24332633
TI  - Validation of the French version of the Suicidal Ideation Questionnaire among
      adolescents.
AB  - Teenage suicide is a major public health issue in Western societies, especially
      in France. An instrument to measure suicidal thoughts in French adolescents and
      thus identify the teenagers at risk is urgently required. The aim of this study
      was to validate a French version of the Suicidal Ideation Questionnaire (SIQ) for
      use with teenagers. Respondents (n=956, age range 14-18.0) completed the SIQ and
      other convergent measures (self-esteem, psychic morbidity, anxiety, and
      personality) for three validation steps (general and clinical samples). A
      confirmatory factor analysis was performed on the SIQ. The study supported a 30
      item one-factor model, similar to the original questionnaire, with moderate model
      fit indices (chi(2)/ddl=3.21; RMSEA=0.05; CFI=0.87; GFI=0.92). Significant
      correlations (-0.22 to 0.74) were found with convergent measures among general
      (n=871) and psychiatric samples (n=38). A high internal consistency was found
      with a reliability coefficient of 0.91. The results confirm the psychometric
      qualities of the questionnaire for French adolescents. 

PMID- 24332632
TI  - Converting positive and negative symptom scores between PANSS and SAPS/SANS.
AB  - The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the
      Assessment of Negative Symptoms (SANS), and the Positive and Negative Syndrome
      Scale for Schizophrenia (PANSS) are the most widely used schizophrenia symptom
      rating scales, but despite their co-existence for 25 years no easily usable
      between-scale conversion mechanism exists. The aim of this study was to provide
      equations for between-scale symptom rating conversions. Two-hundred-and-five
      schizophrenia patients [mean age+/-SD=39.5+/-11.6, 156 males] were assessed with
      the SANS, SAPS, and PANSS. Pearson's correlations between symptom scores from
      each of the scales were computed. Linear regression analyses, on data from 176
      randomly selected patients, were performed to derive equations for converting
      ratings between the scales. Intraclass correlations, on data from the remaining
      29 patients, not part of the regression analyses, were performed to determine
      rating conversion accuracy. Between-scale positive and negative symptom ratings
      were highly correlated. Intraclass correlations between the original positive and
      negative symptom ratings and those obtained via conversion of alternative ratings
      using the conversion equations were moderate to high (ICCs=0.65 to 0.91).
      Regression-based equations may be useful for conversion between schizophrenia
      symptom severity as measured by the SANS/SAPS and PANSS, though additional
      validation is warranted. This study's conversion equations, implemented at
      http:/converteasy.org, may aid in the comparison of medication efficacy studies,
      in meta- and mega-analyses examining symptoms as moderator variables, and in
      retrospective combination of symptom data in multi-center data sharing projects
      that need to pool symptom rating data when such data are obtained using different
      scales.

PMID- 24332634
TI  - [Infiltration of an axillary lymph node by silicone from a ruptured breast
      prothesis].

PMID- 24332635
TI  - [Laparoscopic duodenojejunostomy as a treatment for superior mesenteric artery
      syndrome].

PMID- 24332636
TI  - Cervical esophageal hemangioma.

PMID- 24332637
TI  - Expression patterns of candidate susceptibility genes HNF1beta and CtBP2 in
      prostate cancer: association with tumor progression.
AB  - OBJECTIVES: Genome-wide association studies have identified variants at multiple
      loci associated with prostate cancer (PCa) risk. Some of these loci include
      candidate susceptibility genes, such as MSMB, HNF1beta, and C-terminal-binding
      protein (CtBP2). Except for MSMB, the clinicopathological significance of these
      genes has not been investigated. We therefore aimed to analyze their expression
      in PCa tissues, in relation with tumor progression and aggressiveness. METHODS
      AND MATERIALS: Protein expression was evaluated by immunohistochemistry on tissue
      microarrays containing samples from normal prostate (NL, n = 91), high-grade
      prostatic intraepithelial neoplasia (PIN, n = 61), clinically localized PCa (CLC,
      n = 434), PCa metastases (M, n = 28), and castration-resistant PCa (CRC, n = 49).
      Moreover, mRNA expression for each marker was assessed by quantitative real-time
      polymerase chain reaction, on 53 frozen samples of NL, CLC, and CRC. RESULTS:
      These genes were differentially expressed at the different stages of PCa natural
      history. MSMB expression decreased with disease development and progression. In
      contrast, nuclear HNF1beta and CtBP2 staining significantly increased in the CRC
      and M groups when compared with CLC, together with the transcripts levels. In
      patients with CLC, HNF1beta and CtBP2 nuclear expressions were strongly
      associated with cancer cell proliferation. After adjusting for the Gleason score
      and the pathological stage, none of the candidate genes was significantly
      predictive of recurrence after radical prostatectomy. In patients with CRC, CtBP2
      nuclear staining was associated with shorter overall survival. CONCLUSIONS: The
      decrease of MSMB expression during tumor progression strongly supports its role
      as a tumor-suppressor gene. Although its functions remain to be clarified in PCa
      cells, HNF1beta and CtBP2 are associated with cancer cell proliferation, tumor
      progression, and castration-resistant disease.

PMID- 24332638
TI  - Defining the level of evidence for technology adoption in the localized prostate
      cancer pathway.
AB  - New technologies in prostate cancer are attempting to change the current prostate
      cancer pathway by aiming to reduce harms while maintaining the benefits
      associated with screening, diagnosis, and treatment. In this article, we discuss
      the optimal evaluation that new technologies should undergo to provide level 1
      evidence typically required to change the practice. With this in mind, we focus
      on feasible and pragmatic trials that could be delivered in a timely fashion by
      many centers while retaining primary outcomes that focus on clinically meaningful
      outcomes. 

PMID- 24332639
TI  - Tumor percentage but not number of tumor foci predicts disease-free survival
      after radical prostatectomy especially in high-risk patients.
AB  - OBJECTIVE: To evaluate the predictive value of tumor volume (TV), tumor
      percentage (TP), and number of tumor foci (NF) in patients with prostate cancer.
      The prognostic relevance of TV, TP, and NF as predictors of biochemical
      recurrence (BCR) following radical prostatectomy (RPE) is controversial. PATIENTS
      AND METHODS: The cohort consisted of 758 referred subjects who underwent RPE
      between 2000 and 2005 at the University of Muenster. The mean time of follow-up
      was 62 months. TV, TP, and NF were estimated visually with the assistance of a
      pathologic mapping grid for embedded whole-mount RPE specimens. In addition, TV
      and TP were assessed in a categorized fashion by using quartiles as cutoff
      points. Subgroup analyses for high- and low-risk patients using univariate and
      multivariate Cox proportional hazard analyses for BCR were performed. RESULTS:
      TV, TP, and NF were strongly related to tumor stage, Gleason score, surgical
      margin status, and preoperative prostate-specific antigen (PSA). In univariate
      analysis, all pathologic parameters including TV, TP, and NF were predictive for
      BCR. In multivariate analysis, only TP, tumor stage, and PSA level were
      independent predictors. In subgroup analysis, TP was an independent predictor for
      BCR in the high-risk group but not in the low-risk group. CONCLUSIONS: TP, but
      not TV or NF, was found to be an independent predictor for BCR in patients after
      RPE. TP seems to be more relevant in high-risk patients (i.e., any of the
      following: > pT2, Gleason score > 6, or PSA > 20 ng/ml).

PMID- 24332640
TI  - The effect of BMI on clinicopathologic and functional outcomes after open radical
      prostatectomy.
AB  - OBJECTIVES: To analyze the effect of body mass index (BMI) on pathologic and
      functional outcomes after open radical retropubic prostatectomy. PATIENTS AND
      METHODS: We retrospectively analyzed 2,471 patients who underwent RP.
      Clinicopathologic and patient characteristics were compared with respect to
      patients' BMI (normal weight: BMI < 25 kg/m(2) [n = 795], overweight: BMI >= 25
      kg/m(2) and < 30 kg/m(2) [n = 1305], and obese: BMI >= 30 kg/m(2) [n = 371]).
      Multivariable logistic and linear regression models were used to quantify the
      effect of BMI on pathologic and functional outcomes. RESULTS: Compared with
      normal weight patients, overweight and obese patients demonstrated higher
      pathologic Gleason grade and higher pathologic T stage, without any difference in
      preoperative prostate-specific antigen levels. Overweight and obese men were less
      likely to have a negative surgical margin (odds ratio (OR) 0.74 [confidence
      interval (CI) 0.65-0.84, P<0.001] for overweight men and OR 0.66 [CI 0.49-0.89,
      P<0.01] for obese men) and had a lower rate of postoperative erectile function
      (OR 0.60 [CI 0.48-0.76, P<0.001] for overweight patients and OR 0.34 [CI 0.27
      0.44, P<0.001] for obese patients). Moreover, duration of surgery and
      intraoperative blood loss increased significantly with an increase in BMI. When
      using BMI as a continuous variable, the same trends were demonstrated. However, a
      lower rate of continence was not evident for overweight or obese men.
      CONCLUSIONS: In contrast to many other studies, in this cohort of patients with
      prostate cancer, BMI was an independent risk factor for most analyzed pathologic
      and functional outcomes after radical prostatectomy, including negative surgical
      margin, potency, duration of surgery, and intraoperative blood loss.

PMID- 24332641
TI  - Individualized management of advanced bladder cancer: Where do we stand?
AB  - Despite recent progress in the development of novel targeted therapies in various
      malignancies, the management of advanced urothelial cancer has changed little
      over the past 2 decades. Comorbidities inherent to patients with bladder cancer
      often preclude the use of standard cisplatin-based chemotherapy and underscore
      the need for individualized treatment recommendations and the development of more
      effective therapies. This review discusses current issues relevant to the
      management of patients with locally advanced and metastatic urothelial carcinoma
      of the bladder and highlights recent advances in defining molecular aberrations
      that may ultimately lead to personalized therapeutic decision making. 

PMID- 24332643
TI  - Evaluation of a new quantitative point-of-care test platform for urine-based
      detection of bladder cancer.
AB  - OBJECTIVE: Several commercial point-of-care (POC) tests are available for urine
      based detection of bladder cancer (BC). However, these tests are restricted to
      dichotomized results (positive or negative), which limits their diagnostic value.
      Quantitative protein-based tests offer improved risk stratification but require
      complex methods restricted to specialized centers. Recently, the first
      quantitative POC system based on the detection of cytokeratin fragments became
      available. The aim of the study was to evaluate the diagnostic accuracy of this
      quantitative POC test. PATIENTS AND METHODS: A total of 198 patients having
      symptoms suspicious for BC were included. All patients received urethrocystoscopy
      and upper-tract imaging. Urine samples were analyzed by the urine BC antigen
      (UBC) rapid POC system and evaluated both visually and quantitatively using the
      concile Omega 100 POC reader. For visual evaluation, different thresholds of band
      intensity for considering a test positive were applied. Moreover, the UBC enzyme
      linked immunosorbent assay (ELISA), urine cytology, and the nuclear matrix
      protein 22 BladderChek were performed. Sensitivities and specifities were
      calculated by contingency analyses. Optimal cutoffs of quantitative tests were
      determined by receiver operating characteristic curves. RESULTS: A total of 61
      patients (30.8%) were diagnosed with BC. Visual evaluation of the UBC revealed
      sensitivities of 38.1% to 71.4% with corresponding specificities of 54.1% to
      89.1%, dependent on the threshold of band intensity applied. The quantitative UBC
      rapid showed a sensitivity of 60.7% and a specificity of 70.1% at optimal cutoff
      (area under the curve = 0.68). A constant increase of both the probability of BC
      and high-risk BC with increasing UBC rapid values was observed. UBC
      concentrations determined by the reader significantly correlated with the UBC
      ELISA (P<0.001). The UBC ELISA, the nuclear matrix protein22 BladderChek and
      cytology showed sensitivities of 48.3%, 16.4%, and 51.7% with specificities of
      71.3%, 95.3%, and 78.1%, respectively. CONCLUSION: The UBC rapid in combination
      with a quantitative POC-reader system for the first time enables quantitative
      determination of a BC marker under POC conditions. Diagnostic accuracy is at
      least equivalent to elaborate ELISA-based measurement. The quantitative use of
      the UBC rapid test facilitates risk prediction compared with conventional
      nonquantitative dichotomized POC testing.

PMID- 24332642
TI  - Preclinical and clinical development of DNA vaccines for prostate cancer.
AB  - Prostate cancer is the most commonly diagnosed cancer in the United States. It is
      also the second leading cause of cancer-related death in men, making it one of
      the largest public health concerns today. Prostate cancer is an ideal disease for
      immunotherapies because of the generally slow progression, the dispensability of
      the target organ in the patient population, and the availability of several
      tissue-specific antigens. As such, several therapeutic vaccines have entered
      clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently
      gaining Food and Drug Administration approval after demonstrating overall
      survival benefit in randomized phase III clinical trials. DNA-based vaccines are
      safe, economical, alternative "off-the-shelf" approaches that have undergone
      extensive evaluation in preclinical models. In fact, the first vaccine approved
      in the United States for the treatment of cancer was a DNA vaccine for canine
      melanoma. Several prostate cancer-specific DNA vaccines have been developed in
      the last decade and have shown promising results in early phase clinical trials.
      This review summarizes anticancer human DNA vaccine trials, with a focus on those
      conducted for prostate cancer. We conclude with an outline of special
      considerations important for the development and successful translation of DNA
      vaccines from the laboratory to the clinic. 

PMID- 24332644
TI  - Trends and perioperative outcomes for laparoscopic and robotic nephrectomy using
      the National Surgical Quality Improvement Program (NSQIP) database.
AB  - OBJECTIVES: We sought to examine the trends in perioperative outcomes of kidney
      cancer surgery stratified by type (radical nephrectomy [RN] vs. partial
      nephrectomy [PN]) and approach (open vs. minimally invasive). METHODS: We queried
      the National Surgical Quality Improvement Program database to identify kidney
      cancer operations performed from 2005 to 2011. We examined 30-day perioperative
      outcomes including operative time, transfusion rate, length of stay, major
      morbidity (cardiovascular, pulmonary, renal, and infectious), and mortality.
      RESULTS: A total of 2,902 PN and 5,459 RN cases were identified. The use of PN
      increased over time, accounting for 39% of all nephrectomies in 2011. Minimally
      invasive approaches also increased over time for both RN and PN. Open surgery was
      associated with increased length of stay, receipt of transfusion, major
      complications, and perioperative mortality. Resident involvement and open
      approach were independent predictors of major complications for both PN and RN.
      Additionally, the presence of a medical comorbidity was also a risk factor for
      complications after RN. The overall complication rates decreased for all
      approaches over the study period. CONCLUSIONS: Minimally invasive approaches to
      kidney cancer renal surgery have increased with favorable outcomes. The safety of
      open and minimally invasive PN improved significantly over the study period.
      Although pathologic features cannot be determined from this data set, these data
      show that complications from renal surgical procedures are decreasing in an era
      of increasing use.

PMID- 24332645
TI  - Late gastrointestinal morbidity in patients with stage I-II testicular seminoma
      treated with radiotherapy.
AB  - OBJECTIVES: To define the incidence and risk factors for late gastrointestinal
      (GI) morbidity in patients with testicular seminoma treated with radiotherapy
      (RT). METHODS AND MATERIALS: A retrospective review was conducted of 251 patients
      with stage I or II testicular seminoma treated with curative-intent RT at our
      institution from 1974 to 2009. All patients underwent orchiectomy and
      postoperative external beam RT to the involved nodal basin or at-risk nodal basin
      or both. Potential late GI morbidities that were assessed included endoscopically
      confirmed peptic ulcer disease (PUD), small bowel obstruction (SBO), and biopsy
      confirmed malignancy of the GI tract. The probabilities of these GI morbidities
      were estimated with the Kaplan-Meier method. Univariate analyses were performed
      to examine for associated predictive factors using the Cox proportional hazards
      model. RESULTS: Median age at diagnosis was 36 years (range 18-80). Clinical
      stage was I (n = 199) or II (n = 52). Median abdominopelvic RT dose was 26Gy
      (interquartile range = 25-30). Median follow-up was 15 years (range = 0.1-38).
      PUD risk at 10, 20, and 30 years was 4%, 7%, and 9%, respectively. Age at
      diagnosis (per y, HR = 1.05, 95% CI 1.00-1.09, P = 0.04) and RT dose (per Gy, HR
      = 1.20, 95% CI 1.09-1.31, P<0.01) were associated with risk of PUD. SBO risk at
      10, 20, and 30 years was 2%, 2%, and 3%, respectively. History of inflammatory
      bowel disease was associated with risk of SBO (HR = 43, 95% CI 7-325, P<0.01). GI
      second malignancy risk at 10, 20, and 30 years was 0.5%, 3% and 16%,
      respectively. Age at RT was associated with risk of GI malignancy (per y, HR =
      1.07, 95% CI 1.02-1.14, P = 0.01). CONCLUSIONS: In this patient population, late
      GI morbidity was relatively uncommon, but clinically significant. Refinements of
      treatment strategies may reduce this risk.

PMID- 24332646
TI  - Prognostic risk stratification derived from individual patient level data for men
      with advanced penile squamous cell carcinoma receiving first-line systemic
      therapy.
AB  - BACKGROUND: Prognostic factors in men with penile squamous cell carcinoma (PSCC)
      receiving systemic therapy are unknown. A prognostic classification system in
      this disease may facilitate interpretation of outcomes and guide rational drug
      development. We performed a retrospective analysis to identify prognostic factors
      in men with PSCC receiving first-line systemic therapy for advanced disease.
      PATIENTS AND METHODS: Individual patient level data were obtained from 13
      institutions to study prognostic factors in the context of first-line systemic
      therapy for advanced PSCC. Cox proportional hazards regression analysis was
      conducted to examine the prognostic effect of these candidate factors on
      progression-free survival (PFS) and overall survival (OS): age, stage,
      hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis
      (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance
      status (PS), lymphovascular invasion, precancerous lesion, and surgery following
      chemotherapy. The effect of different treatments was then evaluated adjusting for
      factors in the prognostic model. RESULTS: The study included 140 eligible men.
      Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of
      patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS >= 1,
      47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy.
      The multivariate model of poor prognostic factors included visceral metastases
      (P<0.001) and ECOG PS >= 1 (P<0.001) for both PFS and OS. A risk stratification
      model constructed with 0, 1, and both poor prognostic factors was internally
      validated and demonstrated moderate discriminatory ability (c-statistic of 0.657
      and 0.677 for OS and PFS, respectively). The median OS for the entire population
      was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and
      both risk factors, respectively. Cisplatin-based regimens were associated with
      better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based
      regimens after adjusting for the 2 prognostic factors. CONCLUSIONS: In men with
      advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG
      PS >= 1 were poor prognostic factors. A prognostic model including these factors
      exhibited moderate discriminatory ability for outcomes and warrants external
      validation. Patients receiving cisplatin-based regimens exhibited better outcomes
      compared with noncisplatin-based regimens after adjusting for prognostic factors.

PMID- 24332647
TI  - Does increasing life expectancy affect competing mortality after radical
      prostatectomy?
AB  - OBJECTIVES: In Germany, between 1991 to 1993 and 2004 to 2006, the life
      expectancy in men increased by 4.2 years with greater gains in the eastern part
      of the country. In this study, we investigated to which degree this life
      expectancy increase was translated into lower competing mortality rates after
      radical prostatectomy. METHODS AND MATERIALS: The study sample comprised 6,831
      consecutive patients who underwent radical prostatectomy at the Department of
      Urology of the Dresden University of Technology and the Department of Urology of
      the University of Hamburg/Martini Clinic in the years 1992 to 2005. The median
      age was 63.0 years and the median follow-up was 8.6 years. Three time periods
      (1992-1995, 1996-2001, and 2002-2005) were compared. Competing mortality was the
      study end point. Rates after 8 years were used for comparison. Comparisons of
      mortality rates were made with the 2-sided Wald test. RESULTS: The 8-year
      competing mortality rates decreased from 7.6% (1992-1995) via 5.6% (1996-2001) to
      4.7% (2002-2005 vs. 1992-1995; P = 0.0127). When deaths due to unknown causes (92
      of 969 deaths) were considered as non-prostate cancer competing deaths, the
      corresponding figures were 9.0 % (1992-1995), 6.5% (1996-2001), and 5.6% (2002
      2005) vs. 1992 to 1995; P = 0.0107. The effect was greater in men who are 65
      years of age or older and those of East German origin. CONCLUSIONS: Parallel to
      the increasing life expectancy in Germany, the competing mortality after radical
      prostatectomy decreased in both centers mainly in men who are 65 years of age or
      older. This information may be important for elderly men considering alternatives
      to immediate curative treatment for early prostate cancer.

PMID- 24332648
TI  - Blood- and tissue-based biomarkers for prediction of outcomes in urothelial
      carcinoma of the bladder.
AB  - OBJECTIVES: Urothelial carcinoma of the bladder (UCB) is a highly heterogeneous
      malignancy that causes significant morbidity and mortality. Standard pathologic
      features (stage, grade, and nodal status) are insufficient to predict accurately
      a patient's outcome. Biomarkers could help clinicians provide individualized
      prognostications and allow risk-stratified clinical decision making regarding
      surgical and medical treatment. This review summarizes the existing tissue- and
      blood-based biomarkers in UCB. MATERIAL AND METHODS: A PubMed/Medline search was
      conducted to identify original articles regarding molecular biomarkers and UCB.
      Searches were limited to papers published in English. Keywords included
      urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker,
      staining, cystectomy, recurrence or progression, survival, prediction, and
      prognosis. RESULTS: The articles with the highest level of evidence were selected
      and reviewed, with the consensus of all the authors of this paper. CONCLUSIONS:
      There is no doubt that a panel of biomarkers would eventually improve our
      clinical decision making regarding treatment and follow-up. However, to date, no
      biomarker panel is yet validated for daily clinical practice.

PMID- 24332649
TI  - Quality of physician-patient relationships is associated with the influence of
      physician treatment recommendations among patients with prostate cancer who chose
      active surveillance.
AB  - OBJECTIVE: With growing evidence that some men with prostate cancer (PCa) may be
      overtreated, clinicians need greater knowledge of the factors that influence
      uptake of treatment recommendations in general, and specifically, uptake of
      active surveillance in patients for whom this is an appropriate treatment option.
      The objective of this study was to test the role of the quality of the physician
      patient relationship in the choice to be followed by active surveillance, rather
      than receive definitive therapy (e.g., surgery and radiation). We hypothesized
      that patients would have been more influenced by their physicians' treatment
      recommendations to the degree that they held more positive perceptions of their
      relationship with their physicians, independent of treatment recommended. METHODS
      AND MATERIALS: Patients with PCa (n = 120) being followed with active
      surveillance at a comprehensive cancer center completed self-report assessments
      of their treatment decision-making process. Generalized estimating equations were
      used to model the association between participants' perceptions of their
      relationships with their physicians and influence of these physicians'
      recommendations on their treatment decision. RESULTS: After controlling for the
      type of treatment recommended, Gleason score, and education, 3 predictors, trust
      in the physician, perceived closeness with the physician, and the degree to which
      the physician shared control over treatment decision making, were associated with
      greater influence of physician's treatment recommendation. Receiving a
      recommendation for active surveillance, compared with definitive therapy, was
      also associated with higher perceived trust, closeness, shared control over
      treatment decision making, lower likelihood of having been treated poorly by a
      physician, and greater influence of physician's treatment recommendation.
      CONCLUSIONS: There is increasing concern that patients with relatively less
      aggressive PCa, older age, or serious comorbidities are being unnecessarily
      treated with surgery or radiation, putting them at risk for side effects, and
      contributing to high health care costs. When active surveillance is an
      appropriate course of treatment, the quality of patients' relationships with
      their physicians may be a determinant of following a recommendation for active
      surveillance. Results may have implications for treatment uptake in general,
      indicating that the quality of the physician-patient relationship, including
      trust, closeness, shared decision making--all elements of patient-centered care-
      may be important motivators of treatment adoption and adherence.

PMID- 24332650
TI  - miR-92a/DUSP10/JNK signalling axis promotes human pancreatic cancer cells
      proliferation.
AB  - Pancreatic cancer is one of the most common types of cancers in the whole world
      with a poor prognosis. Finding out how the cancer form and develop is the most
      important way to cure this cancer. miRNAs, 21-22 nucleotides regulatory small non
      coding RNAs, have been found to be critical involved in the growth of pancreatic
      cancer. In this study, we found that miR-92a was up regulated in three kinds of
      human pancreatic cancer cell lines. There is a correlation between miR-92a and
      malignant degree of human pancreatic cancer cell lines. Then we found that miR
      92a was essential for promoting cell proliferation in human pancreatic cancer.
      Inhibition of the function of miR-92a repressed the proliferation of pancreatic
      cancer cells. Further, we found that miR-92a enhanced the activation of JNK
      signalling pathway by directly targeting the JNK signalling inhibitor DUSP10.
      DUSP10 is responsible for miR-92a induced JNK signalling and cell proliferation.
      Altogether, our study showed a miR-92a/DUSP10/JNK signalling pathway that plays
      an important role in regulating the proliferation of pancreatic cancer cells.

PMID- 24332651
TI  - History of operative treatment of forearm diaphyseal fractures.
AB  - Diaphyseal fractures of the forearm have accompanied humanity throughout its
      history. Nonsurgical techniques dominated the treatment for centuries, and
      complications including nonunion and malunion were common. The 19th century
      featured the recognition of distinct injury patterns. With the development of
      anesthesia and antisepsis, the operative treatment became widespread. In 1878,
      Heine described fixation of the diaphyseal nonunion of the distal ulna using an
      intramedullary ivory peg. Parkhill reported on the application of external
      fixation for forearm fractures in 1897-1898. Hansmann published the case of plate
      osteosynthesis of an acute fracture of the radius in 1886. In 1913, Schone
      published the technique of closed intramedullary fixation of diaphyseal fractures
      of the forearm using a silver wire. During the first 2 decades of the 20th
      century, plate osteosynthesis quickly spread across Europe and North America
      owing to the influence of Lambotte and Lane. After the World War II, plate
      osteosynthesis became the surgical treatment of choice for forearm diaphyseal
      fractures. 

PMID- 24332652
TI  - Synthesis and biological evaluation of novel 2-amino-3-aroyl-4-neopentyl-5
      substituted thiophene derivatives as allosteric enhancers of the A1 adenosine
      receptor.
AB  - 2-Amino-3-benzoyl thiophenes have been widely reported to act as allosteric
      enhancers at the A1 adenosine receptor. Their activity can be increased
      considerably by appropriate substitutions at the 4- and 5-positions of the
      thiophene ring. Substituent size at the thiophene C-4 position seemed to be a
      factor closely related to activity, with the 4-neopentyl (2,2-dimethylpropyl)
      substitution showing the greatest enhanced activity. A wide series of 2-amino-3
      aroyl-4-neopentylthiophene derivatives with general structure 3, characterized by
      the presence of different substituents (bromine, aryl and heteroaryl) at the 5
      position of the thiophene ring, have been identified as potent AEs at the A1AR.
      With only one exception, all of the synthesized compounds proved to be superior
      to the reference compound PD 81,723 in a functional assay. Derivatives 3p, 3u,
      3am, 3ap and 3ar were the most active compounds in binding (saturation and
      competition) and functional cAMP studies, being able to potentiate agonist
      [(3)H]CCPA binding to the A1 receptor. 

PMID- 24332653
TI  - New highly toxic bile acids derived from deoxycholic acid, chenodeoxycholic acid
      and lithocholic acid.
AB  - We have prepared a new panel of 23 BA derivatives of DCA, chenodeoxycholic acid
      (CDCA) and lithocholic acid (LCA) in order to study the effect of dual
      substitution with 3-azido and 24-amidation, features individually associated with
      cytotoxicity in our previous work. The effect of the compounds on cell viability
      of HT-1080 and Caco-2 was studied using the 3-[4,5-dimethylthizol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay. Compounds with high potency towards
      reduction of cell viability were further studied using flow cytometry in order to
      understand the mechanism of cell death. Several compounds were identified with
      low micromolar IC50 values for reducing cell viability in the Caco-2 and HT1080
      cell lines, making them among the most potent BA apoptotic agents reported to
      date. There was no evidence of relationship between overall hydrophobicity and
      cytotoxicity supporting the idea that cell death induction by BAs may be
      structure-specific. Compounds derived from DCA caused cell death through
      apoptosis. There was some evidence of selectivity between the two cell lines
      studied which may be due to differing expression of CD95/FAS. The more toxic
      compounds increased ROS production in Caco-2 cells, and co-incubation with the
      antioxidant N-acetyl cysteine blunted pro-apoptotic effects. The properties these
      compounds suggest that there may be specific mechanism(s) mediating BA induced
      cell death. Compound 8 could be useful for investigating this phenomenon.

PMID- 24332654
TI  - Synthesis and anticancer evaluation of 3-substituted quinolin-4-ones and 2,3
      dihydroquinolin-4-ones.
AB  - A series of 3-aryl-5,7-dimethoxyquinolin-4-ones 8 and 3-aryl-5,7-dimethoxy-2,3
      dihydroquinolin-4-ones 13 were synthesized in good yields. Demethylation under a
      range of conditions afforded the corresponding 5-hydroxy and 5,7-dihydroxy
      derivatives. Biological evaluation against a range of cancer cells lines showed
      that the quinolin-4-one scaffold was more cytotoxic than the reduced 2,3
      dihydroquinolin-4-one scaffold. The most active monohydroxy compound 15f
      demonstrated 85.9-99% reduction in cell viability against the cell lines tested. 

PMID- 24332655
TI  - A highly predictive 3D-QSAR model for binding to the voltage-gated sodium
      channel: design of potent new ligands.
AB  - A comprehensive comparative molecular field analysis (CoMFA) model for the
      binding of ligands to the neuronal voltage-gated sodium channel was generated
      based on 67 diverse compounds. Earlier published CoMFA models for this target
      provided MUM ligands, but the improved model described here provided structurally
      novel compounds with low nM IC50. For example, new compounds 94 and 95 had IC50
      values of 129 and 119 nM, respectively.

PMID- 24332656
TI  - Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of
      podophyllotoxin.
AB  - Three series of novel sulfonylurea podophyllotoxin derivatives were designed,
      synthesized, and evaluated for in vitro cytotoxicity against four tumor cell
      lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC50: 1.41-1.76 MUM) and 14e
      (IC50: 1.72-2.01 MUM) showed superior cytotoxic activity compared with etoposide
      (IC50: 2.03 to >20 MUM), a clinically available anticancer drug. Significantly,
      most of the compounds exhibited comparable cytotoxicity against the drug
      resistant tumor cell line KBvin, while etoposide lost activity completely.
      Preliminary structure-activity relationship (SAR) correlations indicated that the
      4'-O-methyl functionality in podophyllotoxin analogues may be essential to
      maintain cytotoxic activity, while an arylsulfonylurea side chain at
      podophyllotoxin's 4beta position can significantly improve cytotoxic activity.

PMID- 24332657
TI  - Identification of novel drug scaffolds for inhibition of SARS-CoV 3-Chymotrypsin
      like protease using virtual and high-throughput screenings.
AB  - We have used a combination of virtual screening (VS) and high-throughput
      screening (HTS) techniques to identify novel, non-peptidic small molecule
      inhibitors against human SARS-CoV 3CLpro. A structure-based VS approach
      integrating docking and pharmacophore based methods was employed to
      computationally screen 621,000 compounds from the ZINC library. The screening
      protocol was validated using known 3CLpro inhibitors and was optimized for speed,
      improved selectivity, and for accommodating receptor flexibility. Subsequently, a
      fluorescence-based enzymatic HTS assay was developed and optimized to
      experimentally screen approximately 41,000 compounds from four structurally
      diverse libraries chosen mainly based on the VS results. False positives from
      initial HTS hits were eliminated by a secondary orthogonal binding analysis using
      surface plasmon resonance (SPR). The campaign identified a reversible small
      molecule inhibitor exhibiting mixed-type inhibition with a K(i) value of 11.1
      MUM. Together, these results validate our protocols as suitable approaches to
      screen virtual and chemical libraries, and the newly identified compound reported
      in our study represents a promising structural scaffold to pursue for further
      SARS-CoV 3CLpro inhibitor development.

PMID- 24332658
TI  - Inhibition of carbonic anhydrases from the extremophilic bacteria
      Sulfurihydrogenibium yellostonense (SspCA) and S. azorense (SazCA) with a new
      series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4
      b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl
      moieties.
AB  - A series of new sulfonamides was prepared starting from 2-oxo-N'-(4
      sulfamoylphenyl)-propanehydrazonoyl chloride, a sulfanilamide derivative, which
      was reacted with aroylhydrazides, amines, or thiols. A library of derivatives
      incorporating aroylhydrazone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2
      (cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was thus synthesized.
      The new compounds were investigated as inhibitors of four alpha-carbonic
      anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I and II, and the
      bacterial ones recently isolated from the extremophilic bacteria
      Sulfurihydrogenibium yellostonense (SspCA) and Sulfurihydrogenibium azorense
      (SazCA). Low nanomolar activity was observed against hCA II (KIs of 0.56-17.1 nM)
      whereas hCA I was less inhibited by these compounds (K(I)s of 86.4 nM-32.8 MUM).
      The bacterial CAs were also effectively inhibited by these derivatives (K(I)s in
      the range of 0.77-234 nM against SazCA, and of 6.2-89.1 against SspCA,
      respectively), with several low nanomolar/subnanomolar inhibitors detected
      against both of them. As SspCA and SazCA are among the most thermostable and
      catalytically active CAs, it is of interest to find modulators of their activity
      for potential biotechnologic applications.

PMID- 24332659
TI  - Romance tourism or female sex tourism?
AB  - BACKGROUND: Love, sex and the female traveller: romance tourism or female sex
      tourism? The phenomenon of women travelling in search of relationships with local
      men in developing countries has been studied for the last 20 years. However, it
      appears little known in travel medicine. METHODS: Relevant literature was found
      through PubMed, Science Direct, ProQuest and Google Scholar. The reference lists
      of selected articles identified further sources. RESULTS: Historical records of
      women travellers to far-away countries abound. Then, as now, women not only
      searched for the erotic 'other' but made romance and sex the purpose of their
      trip. Today, increasing numbers of women travel to destinations in developing
      countries where sex with local men is the main attraction. This pastime raises
      concerns not only for the women themselves but for the local men involved as well
      as their sex partners and the local communities. CONCLUSIONS: Although more
      research is necessary, comparing the criteria that describe men travelling for
      sex and relationships and women travelling for sex and relationships appears to
      suggest that there is very little difference between the two, regardless of what
      the pursuit is called. Women looking for sex with local men are sex tourists,
      too. Recognition of this fact needs to influence the pre and post travel care of
      female travellers.

PMID- 24332660
TI  - Use of Fomepizole in Pediatric Methanol Exposure: The First Case Report in Taiwan
      and a Literature Review.
AB  - Methanol poisoning is rare in the pediatric population, but a delay in diagnosis
      and intervention may cause severe morbidity and mortality. The current therapy
      for methanol poisoning is ethanol or fomepizole, which acts as a competitive
      inhibitor of hepatic alcohol dehydrogenase to inhibit the production of toxic
      metabolites derived from the oxidation of methanol. However, clinical experience
      in pediatric methanol poisoning is limited, and the safety profiles of the
      antidotes have not been established in children, especially in Asian populations.
      This is the first case to describe the use of fomepizole in a child with methanol
      exposure in Taiwan.

PMID- 24332661
TI  - Headache in the pediatric emergency service: a medical center experience.
AB  - BACKGROUND: Headache is a common complaint in children and is one of the most
      common reasons for presentation at a pediatric emergency department (PED). This
      study described the etiologies of patients with headache seen in the PED and
      determined predictors of intracranial pathology (ICP) requiring urgent
      intervention. A secondary objective was to develop rapid, practical tools for
      screening headache in the PED. METHODS: We conducted a retrospective chart review
      of children who presented with a chief complaint of headache at the PED during
      2008. First, we identified possible red flags in the patients' history or
      physical examination and neurological examination findings. Then, we recorded the
      brain computed tomography results. RESULTS: During the study period, 43,913
      visits were made to the PED; in 409 (0.9%) patients, the chief complaint was
      headache. Acute viral, respiratory, and febrile illnesses comprised the most
      frequent cause of headache (59.9%). Six children (1.5%) had life-threatening ICP
      findings. In comparison with the group without ICP, the group with ICP had a
      significantly higher percentage of blurred vision (p = 0.008) and ataxia (p =
      0.002). CONCLUSION: Blurred vision and ataxia are the best clinical parameters to
      predict ICP findings.

PMID- 24332662
TI  - [Are alpha-fetoprotein and other markers useful in the diagnosis and prognosis of
      hepatocellular carcinoma?].

PMID- 24332663
TI  - Retropharyngeal phlegmon in Rosai Dorfman disease.
AB  - Rosai Dorfman disease (RD), also known as sinus histiocytosis with massive
      lymphadenopathy (SHML), is a benign histiocytic proliferative condition of
      unsubstantiated etiology that most often presents as bilateral painless cervical
      lymphadenopathy. Head and neck manifestations of RD are diverse but most commonly
      present as massive cervical lymphadenopathy. Interestingly, a retropharyngeal
      fluid collection has never been described as a sequelae of RD. Our objective is
      to present a novel case of a 9-year old female with RD that suffered from
      recurrent retropharyngeal phlegmon and to discuss diagnostic and treatment
      recommendations for this disease process. 

PMID- 24332664
TI  - Thyroglossal duct cyst and sinuses: a 20-year Los Angeles experience and lessons
      learned.
AB  - BACKGROUND: First described in 1920 and later modified in 1928, the Sistrunk
      procedure substantially reduced the incidence of recurrence of midline neck cysts
      compared with a local excision or cystectomy. The purpose of this study was to
      determine if the rate of recurrence was influenced by performing either a
      'classic' or a 'modified' Sistrunk procedure, if the recurrence rate was
      influenced by the physician's training, how successful we have been in managing
      patients with a recurrence? Finally, is outpatient surgery safe for Sistrunk
      procedures? METHODS: We performed a retrospective review of all patients with a
      thyroglossal duct remnant (TGDR) who were seen at the Children's Hospital Los
      Angeles (CHLA) from 1990 to 2010. The following data were collected: patient age,
      gender, presence or absence of a pre-operative infection, imaging studies, type
      of procedure performed, the attending surgeon's training background, inpatient or
      outpatient status, and complications. RESULTS: A total of 128 patients (61% male,
      39% female) met the inclusion criteria. The age ranged from 2 months to 14 years
      (mean of 5.1 years). A total of 137 procedures were performed; 114 (83.2%) for
      primary and 23 (16.8%) for secondary disease. Complications included post
      operative infection (10.9%), recurrence of disease (6.6%), undesirable scar
      (5.8%), and fistula (2.9%). Surgeons with fellowship-training in pediatric
      otolaryngology had a recurrence rate of 4.0% and surgeons with fellowship
      training in pediatric surgery or pediatric plastic surgery had a recurrence rate
      of 30.1%. Twenty patients had a 'classic' Sistrunk (14.6%) and 117 (85%) had a
      'modified' procedure. Patients were admitted after surgery in 78 cases (56.9%)
      and 59 patients (43.1%) had an outpatient (OPD) procedure. CONCLUSIONS: There is
      no place for cystectomy in the treatment of TGDR. A 'modified' Sistrunk procedure
      is the procedure of choice in both primary and revision cases. Wide local
      excision of recurrences is required and a 'classic' Sistrunk should be
      considered. Specific training to gain an intimate knowledge of the anatomy in and
      around the larynx and experience with multiple cases reduces the incidence of
      recurrence. Outpatient surgery is safe and effective for selected patients who
      undergo a Sistrunk procedure.

PMID- 24332665
TI  - Use of complementary alternative medicine in pediatric otolaryngology patients: a
      survey.
AB  - OBJECTIVE: Limited data are available about complementary alternative medicine
      (CAM) use in children attending otolaryngology services. We investigated the
      pattern of CAM use among children and adolescents attending a pediatric
      otolaryngology clinic. METHODS: A cross-sectional survey. Anonymous
      questionnaires were administered, prior to doctor's admission, to parents
      accompanying young patients attending the pediatric otolaryngology clinic.
      Parents were asked about their general attitude toward CAM and whether they had
      ever consulted or considered a consultation with a CAM therapist. Subsequently,
      CAM users were asked to provide details on CAM modalities used and on their
      overall satisfaction with CAM therapy. RESULTS: Of 308 questionnaires
      administered, 294 parents responded (95% response rate). Ninety-four parents
      (32%) reported considering CAM, or previous or current CAM use. Commonly used CAM
      treatments were acupuncture (44%), homeopathy (36%), and naturopathy (6.7%). CAM
      users assessed success rate as being: successful (37%), unsuccessful (24%) or
      undetermined (39%). Successful treatment was described in terms of cure,
      improvement and better awareness of the problem being addressed. In most cases
      parents stated that the primary physician was aware of CAM use by the child
      (74%). CONCLUSIONS: CAM plays a substantial role among parents of children
      referred to pediatric otolaryngology consultation. The otolaryngologist awareness
      of parents' preference and interest may contribute to decision making regarding
      pediatric patients' management. Further investigations regarding CAM are
      warranted and clinical collaboration with CAM therapists should be considered.

PMID- 24332666
TI  - The role of endoscopy in the treatment of IV type laryngotracheal cleft
      complications after surgical repair.
AB  - Laryngotracheal cleft (LTC) is a rare congenital anomaly. Severe forms of LTC are
      usually treated surgically using extracorporeal circulation. Despite tremendous
      improvement of surgical techniques, postoperative complications are still
      frequent. We report a comprehensive description of an endoscopic approach to
      diagnosis, surgical repair and endoscopic treatment of complications after
      correction in a type IV LTC. 

PMID- 24332667
TI  - Lexical and semantic ability in groups of children with cochlear implants,
      language impairment and autism spectrum disorder.
AB  - OBJECTIVE: Lexical-semantic ability was investigated among children aged 6-9
      years with cochlear implants (CI) and compared to clinical groups of children
      with language impairment (LI) and autism spectrum disorder (ASD) as well as to
      age-matched children with normal hearing (NH). In addition, the influence of age
      at implantation on lexical-semantic ability was investigated among children with
      CI. METHODS: 97 children divided into four groups participated, CI (n=34), LI
      (n=12), ASD (n=12), and NH (n=39). A battery of tests, including picture naming,
      receptive vocabulary and knowledge of semantic features, was used for assessment.
      A semantic response analysis of the erroneous responses on the picture-naming
      test was also performed. RESULTS: The group of children with CI exhibited a
      naming ability comparable to that of the age-matched children with NH, and they
      also possessed a relevant semantic knowledge of certain words that they were
      unable to name correctly. Children with CI had a significantly better
      understanding of words compared to the children with LI and ASD, but a worse
      understanding than those with NH. The significant differences between groups
      remained after controlling for age and non-verbal cognitive ability. CONCLUSIONS:
      The children with CI demonstrated lexical-semantic abilities comparable to age
      matched children with NH, while children with LI and ASD had a more atypical
      lexical-semantic profile and poorer sizes of expressive and receptive
      vocabularies. Dissimilar causes of neurodevelopmental processes seemingly
      affected lexical-semantic abilities in different ways in the clinical groups.

PMID- 24332669
TI  - Management of antiplatelet therapy resistance in cardiac surgery.

PMID- 24332670
TI  - Balloon in the left ventricular outflow tract: a surgical technique for the
      calcified unclampable aorta with aortic insufficiency.

PMID- 24332671
TI  - Discussion.

PMID- 24332668
TI  - Impact of pre-stage II hemodynamics and pulmonary artery anatomy on 12-month
      outcomes in the Pediatric Heart Network Single Ventricle Reconstruction trial.
AB  - OBJECTIVE: To compare the interstage cardiac catheterization hemodynamic and
      angiographic findings between shunt types for the Pediatric Heart Network Single
      Ventricle Reconstruction trial. The trial, which randomized subjects to a
      modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery
      shunt (RVPAS) for the Norwood procedure, demonstrated the RVPAS was associated
      with a smaller pulmonary artery diameter but superior 12-month transplant-free
      survival. METHODS: We analyzed the pre-stage II catheterization data for the
      trial subjects. The hemodynamic variables and shunt and pulmonary angiographic
      data were compared between shunt types; their association with 12-month
      transplant-free survival was also evaluated. RESULTS: Of 549 randomized subjects,
      389 underwent pre-stage II catheterization. A smaller size, lower aortic and
      superior vena cava saturation, and higher ventricular end-diastolic pressure were
      associated with worse 12-month transplant-free survival. The MBTS group had a
      lower coronary perfusion pressure (27 vs 32 mm Hg; P<.001) and greater pulmonary
      blood flow/systemic blood flow ratio (1.1 vs 1.0, P=.009). A greater pulmonary
      blood flow/systemic blood flow ratio increased the risk of death or
      transplantation only in the RVPAS group (P=.01). The MBTS group had fewer shunt
      (14% vs 28%, P=.004) and severe left pulmonary artery (0.7% vs 9.2%, P=.003)
      stenoses, larger mid-main branch pulmonary artery diameters, and greater Nakata
      indexes (164 vs 134, P<.001). CONCLUSIONS: Compared with the RVPAS subjects, the
      MBTS subjects had more hemodynamic abnormalities related to shunt physiology, and
      the RVPAS subjects had more shunt or pulmonary obstruction of a severe degree and
      inferior pulmonary artery growth at pre-stage II catheterization. A lower body
      surface area, greater ventricular end-diastolic pressure, and lower superior vena
      cava saturation were associated with worse 12-month transplant-free survival.

PMID- 24332672
TI  - Intersurgeon variability in long-term outcomes after transatrial repair of
      tetralogy of Fallot: 25 years' experience with 675 patients.
AB  - OBJECTIVE: To compare the long-term reoperation rates among surgeons performing
      transatrial repair of tetralogy of Fallot. METHODS: The data set of 675 patients
      undergoing transatrial repair of tetralogy of Fallot at 1 institution from 1980
      to 2005 was analyzed for intersurgeon differences in the reoperation rates.
      RESULTS: A follow-up period >15 years was available for 5 surgeons, allowing for
      comparison (541 patients; >80 patients/surgeon). The reintervention rate at 10
      years varied from 8.8% (95% confidence interval [CI], 5.3%-14.5%) to 26.7% (95%
      CI, 14.9%-44.9%; hazard ratio, 3.4; P = .001). The procedures of 1 surgeon
      resulted in a reoperation rate of 10.5% at 20 years (95% CI, 5.4%-25.3%). The
      type of reoperation required varied among the surgeons. One surgeon had had no
      reoperations for pulmonary artery stenosis. Of the 5 surgeons, 2 (surgeons 2 and
      5) had equivalent overall 10-year reoperation rates (24.1%, 95% CI, 12.9%-42.3%;
      vs 26.7%, 95% CI, 14.9%-44.9%; P = .32). Surgeon 5 had reoperation almost
      exclusively for right ventricular outflow tract obstruction (20.6%; 95% CI, 12.4%
      33.1%) and surgeon 2 for right ventricular dilation (17.4%; 95% CI, 7.8%-36.3%).
      None of the patients treated by surgeon 5 required implantation of a valved
      conduit. CONCLUSIONS: An analysis of the reoperation rate during the long-term
      follow-up of transatrial repair of tetralogy of Fallot identified variability in
      the outcomes among 5 surgeons. The analysis of these differences suggested that
      an optimal amount of opening of the right ventricular outflow tract can lead to a
      decreased reintervention rate. The analysis of intersurgeon variability in
      outcomes should be encouraged, because it will lead to improvements in cardiac
      surgery outcomes.

PMID- 24332673
TI  - Feelings about food: the ventral tegmental area in food reward and emotional
      eating.
AB  - Overconsumption of high caloric food plays an important role in the etiology of
      obesity. Several factors drive such hedonic feeding. High caloric food is often
      palatable. In addition, when an individual is sated, stress and food-related cues
      can serve as potent feeding triggers. A better understanding of the
      neurobiological underpinnings of food palatability and environmentally triggered
      overconsumption would aid the development of new treatment strategies. In the
      current review we address the pivotal role of the mesolimbic dopamine reward
      system in the drive towards high caloric palatable food and its relation to
      stress- and cue-induced feeding. We also discuss how this system may be affected
      by both established and potential anti-obesity drug targets. 

PMID- 24332674
TI  - Efficacy and safety of ivabradine in patients with severe chronic systolic heart
      failure (from the SHIFT study).
AB  - A post hoc analysis of Systolic Heart failure treatment with the If inhibitor
      ivabradine Trial (SHIFT) explored the efficacy and safety of ivabradine in severe
      heart failure (HF) as denoted by left ventricular ejection fraction (LVEF) <=20%
      and/or New York Heart Association (NYHA) class IV. The SHIFT population (LVEF
      <=35%, heart rate >=70 beats/min, and sinus rhythm) comprised 712 patients with
      severe (defined previously) and 5,973 with less severe (NYHA classes II or III
      and LVEF >20%) HF, all randomized to ivabradine or placebo on a background of
      guideline-defined standard care. The rate of primary composite end point of
      cardiovascular death or HF hospitalization with placebo was higher in severe
      (42%) than less severe (27%) HF (p <0.001). Treatment with ivabradine in severe
      HF was associated with relative risk reductions indistinguishable from those of
      less severe disease for the primary end point (16% reduction), all-cause death
      (22%), cardiovascular death (22%), HF death (37%), and HF hospitalization (17%;
      all p values for interaction: NS). NYHA class improved in 38% (n = 129)
      ivabradine-treated patients with severe HF versus 29% (n = 104) placebo-treated
      patients (p = 0.009). In the 272 patients with severe HF and baseline heart rate
      >=75 beats/min (the indication approved by the European Medicines Agency),
      ivabradine reduced the primary end point by 25% (p = 0.045), HF hospitalization
      by 30% (p = 0.042), and cardiovascular death by 32% (p = 0.034). Ivabradine's
      safety profile in severe HF was indistinguishable from less severe. In
      conclusion, our analysis confirms that heart rate reduction with ivabradine can
      be safely used in severe HF and may improve clinical outcomes independently of
      disease severity.

PMID- 24332675
TI  - Intensity-modulated radiation therapy for head and neck cancer: systematic review
      and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) provides the
      possibility of dose-escalation with better normal tissue sparing. This study was
      performed to assess whether IMRT can improve clinical outcomes when compared with
      two-dimensional (2D-RT) or three-dimensional conformal radiation therapy (3D-CRT)
      in patients with head and neck cancer. METHODS AND MATERIALS: Only prospective
      phase III randomized trials comparing IMRT with 2D-RT or 3D-CRT were eligible.
      Combined surgery and/or chemotherapy were allowed. Two authors independently
      selected and assessed the studies regarding eligibility criteria and risk of
      bias. RESULTS: Five studies were selected. A total of 871 patients were randomly
      assigned for 2D-RT or 3D-CRT (437), versus IMRT (434). Most patients presented
      with nasopharyngeal cancers (82%), and stages III/IV (62.1%). Three studies were
      classified as having unclear risk and two as high risk of bias. A significant
      overall benefit in favor of IMRT was found (hazard ratio - HR=0.76; 95% CI: 0.66,
      0.87; p<0.0001) regarding xerostomia scores grade 2-4, with similar loco-regional
      control and overall survival. CONCLUSIONS: IMRT reduces the incidence of grade 2
      4 xerostomia in patients with head and neck cancers without compromising loco
      regional control and overall survival.

PMID- 24332676
TI  - Excessive risk of cancer and in particular lymphoid malignancy in myasthenia
      gravis patients: a population-based cohort study.
AB  - The exact relationship between myasthenia gravis (MG) and extrathymic
      malignancies has not been established thus far. Occasional cases of MG have been
      reported in association with lymphoma or other lymphoproliferative disorders. To
      determine the risk of extrathymic malignancy with particular attention on
      lymphoid malignancy for MG patients in a large cohort representing 99% of the
      Taiwan population, claims data from the Taiwan National Health Insurance Database
      were used to conduct retrospective cohort analyses. The study cohort comprised
      3671 MG patients who were 10-fold frequency matched by age and sex, and assigned
      the same index year without MG. Cox proportional hazard regression analysis was
      conducted to estimate the risk of cancer. The MG cohort had a 1.74-fold increased
      risk of developing cancer compared to the comparison cohort (HR=1.74, 95% CI=1.47
      2.05). After adjusting for confounders and relative to the cohort, patients with
      MG had a 2.27-fold increased risk of developing lymphoid malignancies (HR=2.27,
      95% CI=1.06-4.88) and a 118.47-fold increased risk of thymus cancer (HR=118.47,
      95%=42.57-329.71). This population based retrospective case-control study
      confirms and extends previous observations on the association between MG and
      lymphoid malignancies. 

PMID- 24332677
TI  - Strategies for conducting adolescent health research in the clinical setting: the
      Mount Sinai Adolescent Health Center HPV experience.
AB  - BACKGROUND: Clinical research with adolescents can be challenging due to issues
      of informed consent, parental involvement, institutional review board
      requirements, and adolescent psychosocial development. These requirements present
      a dilemma, particularly in the area of sexual health research, as adolescents are
      disproportionately affected by sexually transmitted infections such as human
      papillomavirus (HPV). To successfully conduct adolescent research in the clinical
      setting, one requires an awareness of state statutes regarding adolescent
      confidentiality and consent for medical care, and a close partnership with the
      IRB. CASE STUDY: In 2007, the Mount Sinai Adolescent Health Center in
      collaboration with the Albert Einstein College of Medicine developed a
      longitudinal research study to examine the natural history of oral, cervical, and
      anal HPV in an adolescent female population engaged in high-risk sexual
      behaviors. We use this research project as a case study to explore the ethical,
      methodological, and clinical issues related to conducting adolescent health
      research. SUMMARY AND CONCLUSIONS: Several strategies were identified to promote
      adolescent study participation, including: (1) building a research team that is
      motivated to work with adolescents; (2) combining research and patient care
      visits to avoid duplication of services; and (3) establishing a personalized
      communication network with participants. Using these methods, adolescent sexual
      health research can successfully be integrated into the clinical setting. While
      retaining a prospective cohort of adolescents has its challenges, a persistent
      and multi-disciplinary approach can help improve recruitment, sustain
      participation, and acquire critical data that will lead to improved healthcare
      knowledge applicable to understudied populations of adolescents.

PMID- 24332678
TI  - Cross-cultural adaptation, reliability and predictive validity of the Italian
      version of Developmental Coordination Disorder Questionnaire (DCDQ).
AB  - BACKGROUND: Developmental coordination disorder (DCD) is a motor disorder of
      unclear etiology that severely interferes with a child's ability to perform daily
      motor tasks. As a useful alternative to a time-consuming motor test and
      specialist evaluation, parents or teachers can complete motor questionnaires. A
      tool used worldwide to screen motor performance in 4- to 14-year-old children is
      the Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07). AIMS: To
      describe how we translated the Developmental Coordination Disorder Questionnaire
      2007 (DCDQ'07) and adapted it to the Italian population and to test its
      preliminary psychometric properties in Italian children. METHODS: Parents of a
      clinical group of 26 children (5-11 years old) with a diagnosis of DCD and 52
      matched controls completed the DCDQ translated into Italian and adapted for cross
      cultural purposes according to current guidelines. Twenty-four parents of
      typically developing children randomly selected completed the questionnaire twice
      to examine test-retest reliability. RESULTS: The internal consistency value
      (Cronbach alpha) for the Italian DCDQ was 0.94. The Italian DCDQ achieved
      moderate-to-high test-retest reliability (ICC) for 14/15 items and a good
      diagnostic performance for identifying children with DCD (sensitivity 88% and
      specificity 96%). CONCLUSIONS: The Italian DCDQ is a valid screening tool for
      assessing motor performance in 5- to 11-year-old children that merits research in
      a larger sample.

PMID- 24332679
TI  - Altered flexion-relaxation responses exist during asymmetric trunk flexion
      movements among persons with unilateral lower-limb amputation.
AB  - Repetitive exposures to altered gait and movement following lower-limb amputation
      (LLA) have been suggested to contribute to observed alterations in passive tissue
      properties and neuromuscular control in/surrounding the lumbar spine. These
      alterations, in turn, may affect the synergy between passive and active tissues
      during trunk movements. Eight males with unilateral LLA and eight non-amputation
      controls completed quasi-static trunk flexion-extension movements in seven
      distinct conditions of rotation in the transverse plane: 0 degrees  (sagittally
      symmetric), +/-15 degrees , +/-30 degrees , and +/-45 degrees  (sagittally
      asymmetric). Electromyographic (EMG) activity of the bilateral lumbar erector
      spinae and lumbar kinematics were simultaneously recorded. Peak lumbar flexion
      and EMG-off angles were determined, along with the difference ("DIFF") between
      these two angles and the magnitude of peak normalized EMG activities. Persons
      with unilateral LLA exhibited altered and asymmetric synergies between active and
      passive trunk tissues during both sagittally-symmetric and -asymmetric trunk
      flexion movements. Specifically, decreased and asymmetric passive contributions
      to trunk movements were compensated with increases in the magnitude and duration
      of active trunk muscle responses. Such alterations in trunk passive and active
      neuromuscular responses may result from repetitive exposures to abnormal gait and
      movement subsequent to LLA, and may increase the risk for LBP in this population.

PMID- 24332680
TI  - Case-fatality rate associated with measles during pregnancy in Kassala, eastern
      Sudan.

PMID- 24332681
TI  - Lymphocyte activation in silica-exposed workers.
AB  - Exposure to silica dust has been examined as a possible risk factor for
      autoimmune diseases, including systemic sclerosis, rheumatoid arthritis, systemic
      lupus erythematosus and ANCA-associated vasculitis. However, the underlying
      cellular and molecular mechanisms resulting in the increased prevalence of
      autoimmunity remain elusive. To clarify these mechanisms, we studied various
      markers of immune activation in individuals occupationally exposed to silica
      dust, i.e., serum levels of soluble IL-2 receptor (sIL-2R), levels of IL-2, other
      pro- and anti-inflammatory cytokines and lymphoproliferation. Our results
      demonstrate that silica-exposed individuals present important alterations in
      their immune response when compared to controls, as shown by increased serum sIL
      2R levels, decreased production of IL-2 and increased levels of the pro
      inflammatory (IFN-gamma, IL-1alpha, TNF-alpha, IL-6) as well as anti-inflammatory
      (IL-10 and TGF-beta) cytokines. Furthermore, silica-exposed individuals presented
      enhanced lymphoproliferative responses. Our findings provide evidence that the
      maintenance of immune homeostasis may be disturbed in silica-exposed individuals,
      possibly resulting in autoimmune disorders. 

PMID- 24332682
TI  - [The blindness of Piero della Francesca].

PMID- 24332683
TI  - [Charles Bonnet syndrome and the association with dementia].

PMID- 24332684
TI  - [Glaucoma treatment compliance].

PMID- 24332685
TI  - [The blindness of Lord Horatio Nelson's right eye (I)].

PMID- 24332686
TI  - [Vitreomacular traction in patients with exudative age-related macular
      degeneration].

PMID- 24332687
TI  - [Comparison between topical anaesthesia with cocaine versus lidocaine plus
      adrenaline for outpatient laser dacryocystorhinostomy].
AB  - OBJECTIVE: To evaluate the effectiveness of topical anaesthesia with cocaine
      versus lidocaine plus adrenaline for outpatient transcanalicular and endonasal
      dacryocystorhinostomy (TCLDCR) with diode laser under sedation. METHODS: A double
      blind randomised clinical trial was designed using topical anaesthesia for
      outpatient TCLDCR in the treatment of adult epiphora. A total of 92 patients were
      enrolled, and randomly allocated to be operated on under sedation and topical
      anaesthesia with cocaine 4% pledgets versus sedation and topical anaesthesia with
      lidocaine 2% plus 1/100.000 adrenaline pledgets. Main outcome measures were
      postoperative comfort, evaluated by a visual analogue scale, presence of
      secondary effects (blood pressure, heart rate), and resolution of epiphora,
      evaluated by Munk's scale and endoscopic control. RESULTS: Patients in both
      groups reported being comfortable during and immediately after TCLDCR.
      Visualization of the operative field was adequate, and surgery was successfully
      completed in all cases. Complications were more common in the cocaine group:
      Sixteen patients from the cocaine group had high blood pressures, versus 2
      patients from the lidocaine group (RR=8). Mean blood loss was 6.09 ml in cocaine
      group, versus 2.05 ml in lidocaine group (RR=6). Both parameters were
      statistically significant (p=1,1*10(-9)). There were no cases of postoperative
      epistaxis requiring nasal packing or hospital admission in any group. Success
      rate was similar in the 2 groups (86.96% group 1 and 89.13% group 2), after 6
      months of follow-up. CONCLUSIONS: The combination of topical lidocaine and
      adrenaline is more effective for outpatient transcanalicular and endonasal
      dacryocystorhinostomy than topical cocaine. Patient comfort was adequate in both
      groups, but high blood pressure and blood loss more common after cocaine.

PMID- 24332688
TI  - [Association of epiretinal membranes with macular edema in pars planitis].
AB  - INTRODUCTION: Pars planitis (PP) is a form of intermediate uveitis that manifests
      with several posterior segment complications, including cystoid macular edema
      (CME) and epiretinal membrane formation (ERM). On the presence of CME the patient
      is usually treated with anti-inflammatory and/or immunosuppressive drugs. However
      the presence of CME may coexist with ERM formation, and therefore the treatment
      could be different. PURPOSE: To determine the association between ERM and CME in
      PP. MATERIALS AND METHODS: Case control series. The charts of patients diagnosed
      with PP were retrospectively reviewed. All patients had fluorescein angiogram
      (FA) and spectral domain optical coherence tomography (SD-OCT). Presence of ERM
      was determined by SD-OCT, while CME was determined by FA. Contingency tables were
      used to determine the risk of developing CME with ERM. RESULTS: 31 eyes presented
      ERM. 16 eyes presented CME. Relative risk to have CME and ERM was 0.971, with a P
      value of 0.77 (chi(2)). CONCLUSIONS: There is no association between ERM
      formation and the development of CME. There is no evidence to suggest a surgical
      approach as first line of treatment with the presence of ERM in PP.

PMID- 24332689
TI  - Unilateral optic disk edema with central retinal artery and vein occlusions as
      the presenting signs of relapse in acute lymphoblastic leukemia.
AB  - CLINICAL CASE: A 39-year-old man with Philadelphia chromosome-positive acute
      lymphoblastic leukemia (LAL Ph+) developed progressive vision loss to no light
      perception in his right eye. He had optic disk edema and later developed central
      artery and vein occlusions. Pan-photocoagulation, as well as radiotherapy of the
      whole brain were performed in several fractions. Unfortunately the patient died
      of hematological relapse 4 months later. DISCUSSION: Optic nerve infiltration may
      appear as an isolated sign of a leukemia relapse, even before a hematological
      relapse occurs. Leukemic optic neuropathy is a critical sign, not only for
      vision, but also for life, and radiotherapy should be immediately performed
      before irreversible optic nerve damage occurs.

PMID- 24332690
TI  - ["Eyeball licking" or the pleasure of licking the eyes].

PMID- 24332691
TI  - [Descemetorhexis and corneal clearing: a new perspective on the treatment of
      endothelial diseases].

PMID- 24332692
TI  - Orbital involvement by non-Hodgkin lymphoma NK T cells.
AB  - CLINICAL CASE: The case is presented of 37 year-old male with a history of nasal
      obstruction with right rhinorrhea, headache, hearing loss and right exophthalmos
      of 4 months progression. The MRI revealed that the ethmoidal and maxillary
      sinuses contained inflammatory tissue extending into the orbital region. The
      biopsy confirmed a non-Hodgkin lymphoma of natural killer (NK) T cells.
      DISCUSSION: Non-Hodgkin's T NK lymphoma is a rare tumor in the orbital area that
      requires an early detection and multi-disciplinary care to ensure appropriate
      monitoring and treatment.

PMID- 24332693
TI  - [Eye pathologies in Bernardo Strozzi' paintings. The healing of Tobit by Tobias].

PMID- 24332695
TI  - [Anomalocaris: the supervision of the marine giant of the Cambrian period].

PMID- 24332696
TI  - The use of only one hand for the reduction of a temporomandibular joint
      dislocation: a technique suitable for self-reduction.

PMID- 24332697
TI  - Comparison of the frequencies of myocardial edema determined by cardiac magnetic
      resonance in diabetic versus nondiabetic patients having percutaneous coronary
      intervention for ST elevation myocardial infarction.
AB  - The specific mechanisms by which diabetes may affect the myocardial tissue
      response to ischemia are unclear. Our objective was to prospectively quantify the
      degree of myocardial edema in diabetics versus nondiabetics with ST elevation
      myocardial infarction using cardiac magnetic resonance. Fifty-two patients (16
      diabetics and 36 nondiabetics) were enrolled after primary percutaneous coronary
      intervention and underwent cardiac magnetic resonance on a 1.5-T scanner at 48
      hours and 6 months. Myocardial edema was quantified using a T2 mapping technique,
      and infarct size and microvascular obstruction size were assessed by way of a
      contrast-enhanced T1-weighted inversion recovery gradient-echo sequence. The
      infarct segment T2 was elevated in diabetics compared with nondiabetics (59.0 +/-
      8.0 vs 50.8 +/- 3.1 ms, p <0.001) at 48 hours. Multivariate analysis demonstrated
      that diabetes (p <0.001) and symptom-to-balloon time (p = 0.04) were independent
      predictors of the degree of acute myocardial edema. Infarct size was
      nonsignificantly higher in the diabetic group at 48 hours (26.9 +/- 9.4% vs 20.1
      +/- 10.1% of myocardium, p = 0.07) and 6 months (17.1 +/- 6.3% vs 13.4 +/- 6.1%
      of myocardium, p = 0.09). Microvascular obstruction size was equivalent in both
      groups, and there was a trend toward lower myocardial salvage index in diabetics
      (34.2 +/- 11.8 vs 49.6 +/- 13.4, p = 0.08). In conclusion, diabetes is associated
      with increased myocardial edema in the acute phase after primary percutaneous
      coronary intervention. Our results offer insight into the complex processes that
      characterize myocardial tissue response to injury in diabetic patients.

PMID- 24332698
TI  - Overtreatment and undertreatment with anticoagulation in relation to
      cardioversion of atrial fibrillation (the RHYTHM-AF study).
AB  - Antithrombotic therapy is central to the management of atrial fibrillation. This
      analysis from the RHYTHM-atrial fibrillation (RHYTHM-AF) registry explored the
      appropriateness of antithrombotic therapy in relation to stroke risk and atrial
      fibrillation duration in patients with atrial fibrillation. RHYTHM-AF, a
      prospective multinational registry, enrolled consecutive adult patients with
      atrial fibrillation considered for cardioversion. We compared the type of
      antithrombotic therapy administered at the time of cardioversion and at discharge
      with stroke risk ("high stroke risk" defined by CHA2DS2-VASc >1) and duration of
      atrial fibrillation (<=48 vs >48 hours or unknown duration). Of 2,972 patients
      who were cardioverted (34.5% through pharmacologic cardioversion [PCV] and 65.5%
      through electrical cardioversion [ECV]), 65% were at high risk of stroke and 30%
      presented with atrial fibrillation of >48-hour or unknown duration. At the time
      of PCV and ECV, 36% (n = 242) and 84% (n = 1,075) of high-risk patients,
      respectively, were taking vitamin K antagonists or heparin. At discharge, these
      rates increased to 62% (n = 414) and 93% (n = 1,191), respectively. Of all low
      stroke risk patients with short-duration atrial fibrillation undergoing PCV (n =
      260) and ECV (n = 111), 7% (n = 17) and 30% (n = 33), respectively, were taking
      vitamin K antagonists or heparin at the time of cardioversion. At discharge,
      these rates increased to 19% (n = 50) and 40% (n = 44), respectively. In
      conclusion, ECV was frequently performed under appropriate antithrombotic therapy
      for most high-risk patients with atrial fibrillation, whereas PCV was frequently
      performed without appropriate antithrombotic therapy. To enhance
      pericardioversion stroke prevention, cardioversion algorithms should focus less
      on the type of conversion and more on stroke risk factors and atrial fibrillation
      duration.

PMID- 24332700
TI  - [Potential sexual exposure to HIV: experience of the infectious diseases unit of
      Casablanca and literature review].

PMID- 24332699
TI  - Delving into disability in Crohn's disease: dysregulation of molecular pathways
      may explain skeletal muscle loss in Crohn's disease.
AB  - BACKGROUND/AIMS: In Crohn's disease (CD), skeletal muscle mass and function are
      reduced compared to healthy controls, potentially resulting in disability.
      Mechanisms contributing to muscle impairment, and thus potential therapeutic
      targets, are poorly understood. This study aimed to measure and compare skeletal
      muscle size and molecular targets involved in skeletal muscle growth, in CD
      subjects and healthy controls. METHODS: CD (n=27) and healthy (n=22) subjects
      were recruited from the IBD outpatient clinic and via local advertisement
      respectively. Demographics and clinical data were collected via survey and
      interview. Quadriceps muscle cross-sectional area was measured using peripheral
      quantitative CT scanning. Levels of muscle hypertrophy and atrophy signalling
      targets using quantitative PCR and western blotting were measured in muscle
      biopsies. RESULTS: Muscle size was 14% lower (p=0.055) and a 54% lower
      phosphorylated:total (p:t) Akt ratio was measured in the muscle samples (p<0.05),
      indicating an attenuated muscle hypertrophy pathway in CD compared with controls.
      In those with CD, a lower p:t Akt ratio (<0.97) was associated with lower serum
      vitamin D3, lower physical activity indices (49 vs 64 mmol/L, 1.7 vs 2.2*10(6)
      accelerometer counts respectively, each p<0.05) and a trend towards lower serum
      ferritin levels (128 vs 322mg/L, p=0.07), compared with CD subjects with
      normal/high p:t Akt ratios. CONCLUSION: The reduced muscle mass in CD may be
      explained, in part, by impaired activation of muscle protein synthesis pathways,
      notably the IGF1-Akt pathway. Normal vitamin D levels and regular exercise may be
      protective in CD against this trend, though confirmatory longitudinal studies are
      needed.

PMID- 24332701
TI  - [How to monitor today HBV immunotolerant patients and inactive chronic HBV
      carriers?].

PMID- 24332702
TI  - Systemic and local immune response in pigs intradermally and intramuscularly
      injected with inactivated Mycoplasma hyopneumoniae vaccines.
AB  - The systemic and respiratory local immune response induced by the intradermal
      administration of a commercial inactivated Mycoplasma hyopneumoniae whole-cell
      vaccine (Porcilis((r)) MHYO ID ONCE - MSD AH) in comparison with two commercial
      vaccines administered via the intramuscular route and a negative control
      (adjuvant only) was investigated. Forty conventional M. hyopneumoniae-free pigs
      were randomly assigned to four groups (ten animals each): Group A=intradermal
      administration of the test vaccine by using the needle-less IDAL((r)) vaccinator
      at a dose of 0.2 ml; Group B=intramuscular administration of a commercially
      available vaccine (vaccine B); Group C=intramuscular administration of the
      adjuvant only (2 ml of X-solve adjuvant); Group D=intramuscular administration of
      a commercially available vaccine (vaccine D). Pigs were vaccinated at 28 days of
      age. Blood and bronchoalveolar lavage (BAL) fluid samples were collected at
      vaccination (blood only), 4 and 8 weeks post-vaccination. Serum and BAL fluid
      were tested for the presence of antibodies by ELISA test. Peripheral blood
      monomorphonuclear cells (PBMC) were isolated to quantify the number of IFN-gamma
      secreting cells by ELISpot. Moreover, cytokine gene expression from the BAL fluid
      was performed. Total antibodies against M. hyopneumoniae and specific IgG were
      detected in serum of intradermally and intramuscularly (vaccine B only)
      vaccinated pigs at 4 and 8 weeks post-vaccination. M. hyopneumoniae specific IgA
      were detected in BAL fluid from vaccinated animals (Groups A and B) but not from
      controls and animals vaccinated with the bacterin D (p<0.05). Significantly
      higher gene expression of IL-10 was observed in the BAL fluid at week 8 post
      vaccination in the intradermally vaccinated pigs (p<0.05). The results support
      that the intradermal administration of an adjuvanted bacterin induces both
      systemic and mucosal immune responses. Moreover, the intramuscularly administered
      commercial vaccines each had a different ability to stimulate the immune response
      both systemically and locally.

PMID- 24332703
TI  - Identification and characterization of methicillin-resistant Staphylococcus
      aureus (MRSA) from Austrian companion animals and horses.
AB  - The aim of this study was to investigate the antimicrobial resistance, resistance
      gene patterns and genetic relatedness of a collection of Austrian methicillin
      resistant Staphylococcus aureus (MRSA) isolates from companion animals and
      horses. A total of 89 non-repetitive MRSA isolates collected during routine
      veterinary microbiological examinations from April 2004 to the end of 2012, and
      one isolate from 2013 were used for this study. The presence of mecA and other
      resistance genes was confirmed by PCR. Isolates were genotyped by spa typing, two
      multiple-locus variable-number tandem repeat analyses (MLVA) analyses, SCCmec
      typing and multilocus sequence typing (MLST). PCR targeting Panton-Valentine
      leukocidin (PVL) and detection of staphylococcal enterotoxins (SE), toxic shock
      syndrome toxin (TSST) was performed using PCR assays. Antimicrobial
      susceptibility testing was performed. Five sequence types (STs-ST398, ST254,
      ST22, ST5 and ST1), SCCmec types II, IVa, V, and non-type-abele, 8 spa-types
      (t003, t011, t036, t127, t386, t1348, and t4450), and two isolates could not be
      assigned, 21 MLVA-14Orsay types Multiplex-PCR MLVA (mMLVA) displayed 17 different
      MLVA types. The present study is the most comprehensive dealing with MRSA from
      Austrian companion animals and horses. The results confirm that MRSA ST398 is
      present in a wide range of animal species and is predominant especially in
      horses. In other companion animals it is unclear whether the infections with the
      different MRSA isolates investigated in the present study truly represents a rare
      phenomenon or may be an emerging problem in companion animals.

PMID- 24332704
TI  - Glans meatus proportion in hypospadias versus normal: does marking reference
      points impact outcome?
AB  - OBJECTIVE: The aims of this study were to assess anatomical landmarks with
      reference to urethral meatus and glans in hypospadias and compare the findings
      with those of healthy individuals, and to assess whether marking reference points
      helps in improving outcome. METHODS: 1. Patients who underwent repair for
      hypospadias had reference points marked. Vertical meatal length, ventral glans
      closure and glans meatus proportion were derived, and the values compared with
      those obtained from healthy boys. 2. The outcomes of TIP repair after marking
      reference points (Group I) were compared with those of a similar group without
      skin markings (Group II). RESULTS: 1. There was significant difference in the age
      distribution of hypospadiac patients and healthy individuals, reflected in the
      meatal length and ventral glans closure. However, there was no significant
      difference in glans meatus proportion. 2. The fistula rate was 2/35 (5.7%) in
      group I compared with 5/47 (10.5%) in group II. The meatal stenosis was 2/35
      (5.7%) in group I and 4/47 (8.5%) in group II. CONCLUSION: 1. Anatomical
      landmarks in hypospadias are similar to those found in healthy individuals. 2.
      Marking reference points prior to incision helps to reduce the rate of meatal
      stenosis and fistula.

PMID- 24332705
TI  - Reassessment of the importance of mucins in determining sputum properties in
      cystic fibrosis.
AB  - BACKGROUND: There is conflicting evidence about the importance of airway mucins
      (MUC5AC and MUC5B) in determining physical properties of sputum in cystic
      fibrosis (CF). We studied the effects of endogenous degradation of mucins on CF
      sputum elasticity and apparent mucin concentrations. METHODS: Elastic shear
      moduli (G') and mucin concentrations in sputum of 12 CF patients were measured
      before and after incubation at 37 degrees C for 60min. RESULTS: G' fell from a
      median of 5.98 to 4.70Pa (p=0.01). There were significant falls in MUC5AC (8.2 to
      5.2MUg/ml, p=0.02) and MUC5B (17.3 to 12.5MUg/ml, p=0.02) over the same period,
      and associated decrease in molecular weight and size. CONCLUSIONS: Sputum is not
      inert and degradation reduces apparent mucin concentrations and sputum
      elasticity. Even if care is taken to process samples rapidly, sputum may
      therefore differ from secretions retained in airways. Previous studies may have
      underestimated the role of mucins in CF sputum.

PMID- 24332706
TI  - Low serum bilirubin concentration is a novel risk factor for the development of
      albuminuria in patients with type 2 diabetes.
AB  - OBJECTIVE: Bilirubin has been recognized as an important endogeneous antioxidant.
      Previous studies reported that bilirubin could prevent atherosclerosis. The aim
      of this study was to investigate if serum bilirubin concentration could be a
      predictor for the development of albuminuria in patients with type 2 diabetes.
      MATERIALS AND METHODS: We measured serum bilirubin in 320 consecutive patients
      with normoalbuminuria. We performed follow-up study to assess the development of
      albuminuria, mean interval of which was 3.2+/-0.9years. Cox proportional hazards
      regression was used to examine the relationship between serum bilirubin
      concentration and the development of albuminuria. RESULTS: During follow-up
      duration, 43 patients have developed albuminuria. In multivariate analysis, after
      adjusting for comprehensive risk factors, the risk of developing albuminuria was
      higher in the lowest quartile of serum bilirubin concentrations than that in the
      highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI,
      1.65 to 24.93). CONCLUSIONS: Low serum bilirubin concentration could be a novel
      risk factor for the development of albuminuria in patients with type 2 diabetes.

PMID- 24332707
TI  - Bariatric surgery in severely obese adolescents improves major comorbidities
      including hyperuricemia.
AB  - OBJECTIVE: Serum uric acid (sUA) is believed to contribute to the pathogenesis of
      metabolic comorbidities like hypertension, insulin-resistance (IR) and
      endothelial dysfunction (EDF) in obese children. The present pilot study
      investigated the association between sUA concentrations and loss of body weight
      following laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y-gastric
      bypass (RYGB) in severely obese adolescents. MATERIALS/METHODS: 10 severely obese
      adolescents underwent either LSG (n=5) or RYGB (n=5). 17 normal weight, healthy,
      age- and gender-matched adolescents served as a normal weight peer group (NWPG).
      Pre- and 12 months postoperatively, sUA and relevant metabolic parameters
      (glucose homeostasis, transaminases, lipids) were compared. RESULTS:
      Preoperatively, sUA was significantly elevated in patients with severe obesity
      compared to NWPG. Twelve months after LSG and RYGB, a significant decrease in
      sUA, BMI, CVD risk factors, hepatic transaminases, and HOMA-IR was observed.
      Reduction in SDS-BMI significantly correlated with changes in sUA. CONCLUSIONS:
      sUA levels and metabolic comorbidities improved following bariatric surgery in
      severely obese adolescents. The impact of changes in sUA on long-term clinical
      complications of childhood obesity deserves further study.

PMID- 24332708
TI  - [The blindness in Lord Horatio Nelson's right eye (II)].

PMID- 24332709
TI  - [Undifferentiated high-grade pleomorphic sarcoma of the orbit: a case report].
AB  - CASE REPORT: A 27-year-old female presented to us with a complaint of proptosis
      of her right eye. Imaging tests showed an extraconal mass in the medial orbital
      wall, which affected the medial rectus. The tumor was removed and adjuvant
      radiotherapy was required. The histological examination showed an
      undifferentiated high-grade pleomorphic sarcoma of the orbit. There has not been
      recurrence after 6 years of follow-up. DISCUSSION: Undifferentiated high-grade
      pleomorphic sarcoma is an uncommon cause of malignant orbital mass. It grows fast
      and can metastasize, so extension studies are required. Surgical excision is the
      treatment of choice.

PMID- 24332710
TI  - [Prevalence and inappropriateness of urinary catheters in Internal Medicine].

PMID- 24332711
TI  - [Consensus statement: recommendations for the management of metabolic bone
      disease in human immunodeficiency virus patients].
AB  - OBJECTIVE: To provide practical recommendations for the evaluation and treatment
      of metabolic bone disease in human immunodeficiency virus (HIV) patients.
      PARTICIPANTS: Members of scientific societies related to bone metabolism and HIV:
      Grupo de Estudio de Sida (GeSIDA), Sociedad Espanola de Endocrinologia y
      Nutricion (SEEN), Sociedad Espanola de Investigacion Osea y del Metabolismo
      Mineral (SEIOMM), and Sociedad Espanola de Fractura Osteoporotica (SEFRAOS).
      METHODS: A systematic search was carried out in PubMed, and papers in English and
      Spanish with a publication date before 28 May 2013 were included. Recommendations
      were formulated according to GRADE system (Grading of Recommendations,
      Assessment, Development, and Evaluation) setting both their strength and the
      quality of supporting evidence. Working groups were established for each major
      part, and the final resulting document was later discussed in a face-to-face
      meeting. All the authors reviewed the final written document and agreed with its
      content. CONCLUSIONS: The document provides evidence-based practical
      recommendations on the detection and treatment of bone disease in HIV-infected
      patients.

PMID- 24332712
TI  - [Clostridium difficile infection due to ribotype 027: description of an imported
      case in Spain].

PMID- 24332713
TI  - [KIR-HLA class i and pulmonary tuberculosis in the Amerindian population in
      Chaco, Argentina].
AB  - INTRODUCTION: The susceptibility to pulmonary tuberculosis (TB) is
      multifactorial, thus genetic factors such as HLA and immunoglobulins-like killer
      receptors (KIR) could be predisposed to the development of the disease. Aim To
      evaluate whether any HLA classi allele and its combination with KIR could be
      related to the development of TB in the Wichi Amerindian community in north
      eastern Argentina. METHODS: A cohort study was conducted that included 18
      families, 35 individuals affected with TB, 84 cohabiting families, and 63
      controls of the same ethnic group. A and B loci of HLA classi were typed by
      generic PCR followed by reverse hybridization (Dynal), locus C by PCR-SSOP. KIR
      receptors were studied using sequence specific PCR. RESULTS: There was a highly
      significant association with allele B*35:19/47 in TB vs. household contacts
      [Pc=0.0051] and vs. controls [Pc=0.0033], and with allele HLA-C*03 in TB vs.
      household contacts [Pc=0.014] and vs. controls [Pc=0.0033]. KIR receptors had
      shown increased KIR2DL3/KIR2DL3 frequency in combination with the C1 group of HLA
      C (P=.018). HLA-C*03 belongs to C1 group, and this combination could have a
      strong inhibitory action on the infected cell. CONCLUSION: HLA-B35:19/47-C*03
      haplotype could be a susceptibility factor to TB and KIR2DL3-HLA-C1 combination
      have an inhibitory capacity on NK cells, and might contribute to the course of
      the infection by Mycobacterium tuberculosis.

PMID- 24332714
TI  - Occupational exposure to bloodborne pathogens in IR--risks, prevention, and
      recommendations: a joint guideline of the Society of Interventional Radiology and
      Cardiovascular and Interventional Radiological Society of Europe.

PMID- 24332715
TI  - Structural details of human tuba recruitment by InlC of Listeria monocytogenes
      elucidate bacterial cell-cell spreading.
AB  - The human pathogen Listeria monocytogenes is able to directly spread to
      neighboring cells of host tissues, a process recently linked to the virulence
      factor InlC. InlC targets the sixth SH3 domain (SH3-6) of human Tuba, disrupting
      its physiological interaction with the cytoskeletal protein N-WASP. The resulting
      loss of cortical actin tension may slacken the junctional membrane, allowing
      protrusion formation by motile Listeria. Complexes of Tuba SH3-6 with
      physiological partners N-WASP and Mena reveal equivalent binding modes but
      distinct affinities. The interaction surface of the infection complex InlC/Tuba
      SH3-6 is centered on phenylalanine 146 of InlC stacking upon asparagine 1569 of
      Tuba. Replacing Phe146 by alanine largely abrogates molecular affinity and in
      vivo mimics deletion of inlC. Collectively, our findings indicate that InlC
      hijacks Tuba through its LRR domain, blocking the peptide binding groove to
      prevent recruitment of its physiological partners. 

PMID- 24332716
TI  - A structure of a collagen VI VWA domain displays N and C termini at opposite
      sides of the protein.
AB  - Von Willebrand factor A (VWA) domains are versatile protein interaction domains
      with N and C termini in close proximity placing spatial constraints on overall
      protein structure. The 1.2 A crystal structures of a collagen VI VWA domain and a
      disease-causing point mutant show C-terminal extensions that place the N and C
      termini at opposite ends. This allows a "beads-on-a-string" arrangement of
      multiple VWA domains as observed for ten N-terminal domains of the collagen VI
      alpha3 chain. The extension is linked to the core domain by a salt bridge and two
      hydrophobic patches. Comparison of the wild-type and a muscular dystrophy
      associated mutant structure identifies a potential perturbation of a protein
      interaction interface and indeed, the secretion of mutant collagen VI tetramers
      is affected. Homology modeling is used to locate a number of disease-associated
      mutations and analyze their structural impact, which will allow mechanistic
      analysis of collagen-VI-associated muscular dystrophy phenotypes. 

PMID- 24332717
TI  - Structure, functional characterization, and evolution of the dihydroorotase
      domain of human CAD.
AB  - Upregulation of CAD, the multifunctional protein that initiates and controls the
      de novo biosynthesis of pyrimidines in animals, is essential for cell
      proliferation. Deciphering the architecture and functioning of CAD is of interest
      for its potential usage as an antitumoral target. However, there is no detailed
      structural information about CAD other than that it self-assembles into hexamers
      of ~1.5 MDa. Here we report the crystal structure and functional characterization
      of the dihydroorotase domain of human CAD. Contradicting all assumptions, the
      structure reveals an active site enclosed by a flexible loop with two Zn2+ ions
      bridged by a carboxylated lysine and a third Zn coordinating a rare histidinate
      ion. Site-directed mutagenesis and functional assays prove the involvement of the
      Zn and flexible loop in catalysis. Comparison with homologous bacterial enzymes
      supports a reclassification of the DHOase family and provides strong evidence
      against current models of the architecture of CAD.

PMID- 24332718
TI  - A self-sequestered calmodulin-like Ca2+ sensor of mitochondrial SCaMC carrier and
      its implication to Ca2+-dependent ATP-Mg/P(i) transport.
AB  - The mitochondrial carriers play essential roles in energy metabolism. The short
      Ca2+-binding mitochondrial carrier (SCaMC) transports ATP-Mg in exchange for Pi
      and is important for activities that depend on adenine nucleotides. SCaMC adopts,
      in addition to the transmembrane domain (TMD) that transports solutes, an
      extramembrane N-terminal domain (NTD) that regulates solute transport in a Ca2+
      dependent manner. Crystal structure of the Ca2+-bound NTD reveals a compact
      architecture in which the functional EF hands are sequestered by an endogenous
      helical segment. Nuclear magnetic resonance (NMR) relaxation rates indicated that
      removal of Ca2+ from NTD results in a major conformational switch from the rigid
      and compact Ca2+-bound state to the dynamic and loose apo state. Finally, we
      showed using surface plasmon resonance and NMR titration experiments that free
      apo NTDs could specifically interact with liposome-incorporated TMD, but that
      Ca2+ binding drastically weakened the interaction. Our results together provide a
      molecular explanation for Ca2+-dependent ATP-Mg flux in mitochondria.

PMID- 24332719
TI  - American Society of Biomechanics Clinical Biomechanics Award 2012: plantar shear
      stress distributions in diabetic patients with and without neuropathy.
AB  - BACKGROUND: The exact pathology of diabetic foot ulcers remains to be resolved.
      Evidence suggests that plantar shear forces play a major role in diabetic
      ulceration. Unfortunately, only a few manuscripts exist on the clinical
      implications of plantar shear. The purpose of this study was to compare global
      and regional peak plantar stress values in three groups; diabetic patients with
      neuropathy, diabetic patients without neuropathy and healthy control subjects.
      METHODS: Fourteen diabetic neuropathic patients, 14 non-neuropathic diabetic
      control and 11 non-diabetic control subjects were recruited. Subjects walked on a
      custom-built stress plate that quantified plantar pressures and shear. Four
      stress variables were analyzed; peak pressure, peak shear, peak pressure-time and
      shear-time integral. FINDINGS: Global peak values of peak shear (p = 0.039),
      shear-time integral (p = 0.002) and pressure-time integral (p = 0.003) were
      significantly higher in the diabetic neuropathic group. The local peak shear
      stress and shear-time integral were also significantly higher in diabetic
      neuropathic patients compared to both control groups, in particular, at the
      hallux and central forefoot. The local peak pressure and pressure-time integral
      were significantly different between the three groups at the medial and lateral
      forefoot. INTERPRETATION: Plantar shear and shear-time integral magnitudes were
      elevated in diabetic patients with peripheral neuropathy, which indicates the
      potential clinical significance of these factors in ulceration. It is thought
      that further investigation of plantar shear would lead to a better understanding
      of ulceration pathomechanics, which in turn will assist researchers in developing
      more effective preventive devices and strategies.

PMID- 24332720
TI  - Validity, reliability and responsiveness of the French language translation of
      the Western Ontario Shoulder Instability Index (WOSI).
AB  - BACKGROUND: The WOSI (Western Ontario Shoulder Instability Index) is a self
      administered quality of life questionnaire designed to be used as a primary
      outcome measure in clinical trials on shoulder instability, as well as to measure
      the effect of an intervention on any particular patient. It is validated and is
      reliable and sensitive. As it is designed to measure subjective outcome, it is
      important that translation should be methodologically rigorous, as it is subject
      to both linguistic and cultural interpretation. OBJECTIVE: To produce a French
      language version of the WOSI that is culturally adapted to both European and
      North American French-speaking populations. MATERIALS AND METHODS: A validated
      protocol was used to create a French language WOSI questionnaire (WOSI-Fr) that
      would be culturally acceptable for both European and North American French
      speaking populations. Reliability and responsiveness analyses were carried out,
      and the WOSI-Fr was compared to the F-QuickDASH-D/S (Disability of the Arm,
      Shoulder and Hand-French translation), and Walch-Duplay scores. RESULTS: A French
      language version of the WOSI (WOSI-Fr) was accepted by a multinational committee.
      The WOSI-Fr was then validated using a total of 144 native French-speaking
      subjects from Canada and Switzerland. Comparison of results on two WOSI-Fr
      questionnaires completed at a mean interval of 16 days showed that the WOSI-Fr
      had strong reliability, with a Pearson and interclass correlation of r=0.85
      (P=0.01) and ICC=0.84 [95% CI=0.78-0.88]. Responsiveness, at a mean 378.9 days
      after surgical intervention, showed strong correlation with that of the F
      QuickDASH-D/S, with r=0.67 (P<0.01). Moreover, a standardized response means
      analysis to calculate effect size for both the WOSI-Fr and the F-QuickDASH-D/S
      showed that the WOSI-Fr had a significantly greater ability to detect change (SRM
      1.55 versus 0.87 for the WOSI-Fr and F-QuickDASH-D/S respectively, P<0.01). The
      WOSI-Fr showed fair correlation with the Walch-Duplay. DISCUSSION: A French
      language translation of the WOSI questionnaire was created and validated for use
      in both Canadian and Swiss French-speaking populations. This questionnaire will
      facilitate outcome assessment in French-speaking settings, collaboration in
      multinational studies and comparison between studies performed in different
      countries. TYPE OF STUDY: Multicenter cohort study. LEVEL OF EVIDENCE: II.

PMID- 24332721
TI  - An arthroscopic check valve release improves knee intrameniscal cyst symptoms in
      adolescent: a case report.
AB  - Intrameniscal cysts begin with the flow of synovial fluid from a meniscal tear in
      one direction, enlarging probably as a result of an on-and-off valve mechanism of
      the tear flap. The current available literature focuses primarily on the
      necessity for surgery, however a large meniscus resection to remove cysts may
      place an additional burden on menisci, leading ultimately to knee joint
      degenerative changes. In this article, we present a rare case of intrameniscal
      cysts with an isolated horizontal meniscal tear in an adolescent, and describe a
      new arthroscopic procedure for treating this type of intrameniscal cyst. We
      performed arthroscopic partial release of the meniscal tear check-valve
      mechanism, preventing further intrameniscal cyst expansion. The patient's
      clinical symptoms improved, and this procedure may also be useful in treating
      intrameniscal cysts with an isolated horizontal meniscal tear and can be
      considered as an option to preserve meniscal function and minimize degenerative
      arthritis in young athletes. 

PMID- 24332722
TI  - The impact of age on the epidemiology of atrial fibrillation hospitalizations.
AB  - BACKGROUND: Given that 4 million individuals in the United States have atrial
      fibrillation, understanding the epidemiology of this disease is crucial. We
      sought to identify and characterize the impact of age on national atrial
      fibrillation hospitalization patterns. METHODS: The study sample was drawn from
      the 2009-2010 Nationwide Inpatient Sample. Patients hospitalized with a principal
      International Classification of Diseases, 9th Revision discharge diagnosis of
      atrial fibrillation were included. Patients were categorized as "older" (>=65
      years) or "younger" (<65 years) for the purposes of analysis. The outcomes
      measured included hospitalization rate, length of stay, in-hospital mortality,
      and discharge status. RESULTS: We identified 192,846 atrial fibrillation
      hospitalizations. There was significant geographic variation in hospitalizations
      for both younger and older age groups. States with high hospitalizations differed
      from those states known to have high stroke mortality. Younger patients (33% of
      the sample) were more likely to be obese (21% vs 8%, P < .001) and to use alcohol
      (8% vs 2%, P < .001). Older patients were more likely to have kidney disease (14%
      vs 7%, P < .001). Both age groups had high rates of hypertension and diabetes.
      Older patients had higher in-hospital mortality and were more likely to be
      discharged to a nursing or intermediate care facility. CONCLUSIONS: Younger
      patients account for a substantial minority of atrial fibrillation
      hospitalizations in contemporary practice. Younger patients are healthier, with a
      different distribution of risk factors, than older patients who have higher
      associated morbidity and mortality.

PMID- 24332723
TI  - A 'posterior circulation stroke' that benefits from vitamins.

PMID- 24332724
TI  - Exogenous lipoid pneumonia (fire-eater's lung).

PMID- 24332725
TI  - Interpreting laboratory results in transgender patients on hormone therapy.
AB  - BACKGROUND: Clinical guidelines recommend laboratory monitoring of transgender
      persons on cross-sex hormone therapy, but gender-specific reference intervals
      leave clinicians with the dilemma of deciding what is "normal" for each patient.
      The goal of this study was to identify consistent changes in measurands with
      hormone therapy and determine which reference interval is appropriate. METHODS:
      Laboratory data were abstracted from the medical records of 55 male-to-female
      patients on hormone therapy and compared with 20 male and 20 female
      nontransgender subjects. RESULTS: Hemoglobin, hematocrit, and low-density
      lipoprotein resembled female values (P < .005), while alkaline phosphatase,
      potassium, and creatinine resembled male values (P < .05). Triglycerides were
      higher (P < .005) than either the male or female groups. The remainder of the
      measurands showed no differences. CONCLUSIONS: Use of correct reference intervals
      in interpreting laboratory results reduces the risk of testing-related diagnostic
      error. Preliminary data suggest that new reference intervals need to be
      established for transgender patients.

PMID- 24332726
TI  - Clinical features of precocious acute coronary syndrome.
AB  - BACKGROUND: Acute coronary syndrome due to acute plaque rupture has been well
      described and is associated with established risk factors, including
      hypertension, diabetes mellitus, hyperlipidemia, and smoking. The prevalence of
      these risk factors in very young patients (aged <=35 years) is not well known,
      and they may have other nontraditional risk factors. We hypothesized that acute
      coronary syndrome in very young patients may represent a thrombotic event
      independent of underlying atherosclerotic disease. METHODS: We performed a dual
      institution, retrospective study of consecutive patients aged <=35 years who
      presented with acute coronary syndrome and underwent coronary angiography from
      January 2000 to December 2011. Standard demographics, risk factors, and detailed
      angiographic information were obtained. RESULTS: A total of 124 patients met
      inclusion criteria. The mean age was 31 +/- 4 years for both sexes. Approximately
      half (49%) of the patients were obese (body mass index >=30 kg/m(2)); 90% of
      patients had at least 1 traditional risk factor, most commonly hyperlipidemia
      (63%) and smoking (60%); 52% of patients underwent re-vascularization, of which
      94% were by percutaneous coronary intervention, and 42.9% of patients had
      intracoronary thrombus, of whom approximately one third had no detectable
      underlying coronary disease. CONCLUSIONS: Very young patients with acute coronary
      syndrome tend to be obese, with a high prevalence of smoking and hyperlipidemia.
      The presence of thrombus in the absence of underlying coronary disease suggests a
      thromboembolic event or de novo thrombotic occlusion, which may reflect primary
      hemostatic dysfunction in a considerable number of these patients.

PMID- 24332727
TI  - Examining the relationship between internal medicine resident moonlighting and IM
      ITE performance.

PMID- 24332728
TI  - Use of organic substrates as electron donors for biological sulfate reduction in
      gypsiferous mine soils from Nakhon Si Thammarat (Thailand).
AB  - Soils in some mining areas contain a high gypsum content, which can give adverse
      effects to the environment and may cause many cultivation problems, such as a low
      water retention capacity and low fertility. The quality of such mine soils can be
      improved by reducing the soil's gypsum content. This study aims to develop an
      appropriate in situ bioremediation technology for abbreviating the gypsum content
      of mine soils by using sulfate reducing bacteria (SRB). The technology was
      applied to a mine soil from a gypsum mine in the southern part of Thailand which
      contains a high sulfate content (150 g kg(-1)). Cheap organic substrates with low
      or no cost, such as rice husk, pig farm wastewater treatment sludge and coconut
      husk chips were mixed (60:20:20 by volume) and supplied to the soil as electron
      donors for the SRB. The highest sulfate removal efficiency of 59% was achieved in
      the soil mixed with 40% organic mixture, corresponding to a reduction of the soil
      gypsum content from 25% to 7.5%. For economic gains, this treated soil can be
      further used for agriculture and the produced sulfide can be recovered as the
      fertilizer elemental sulfur.

PMID- 24332729
TI  - Natural xenobiotics to prevent cyanobacterial and algal growth in freshwater:
      contrasting efficacy of tannic acid, gallic acid, and gramine.
AB  - Allelochemical action against planktonic phototrophs is one central issue in
      freshwater ecology and quality management. To determine some basic mechanisms of
      this toxic action, we exposed the coccal green alga, Desmodesmus armatus, and the
      coccal cyanobacterium, Microcystis aeruginosa, in a batch culture well-supplied
      with carbon dioxide to increasing concentrations of the polyphenols tannic acid
      and gallic acid and the alkaloid gramine. The phototrophs were checked after 2d
      and at the end of the culture for biomass-based growth rates, cell volume,
      maximum quantum yield of photosystem II (PhiPSIImax), chlorophyll a content
      (chla) after 2d and at the end of the culture, and lipid peroxidation only at the
      end of the culture. During the culture, the pH rose from 7.64 to 10.95, a pH
      characteristic of eutrophic freshwater bodies during nuisance algal blooms. All
      xenobiotics reduced the growth rate, PhiPSIImax, and chla during the first 2d
      with M. aeruginosa being more sensitive to the polyphenols than D. armatus. The
      efficacy of the polyphenols declined with increasing pH, indicating potential
      polymerization and corresponding reduced bioavailability of the polyphenols. In
      contrast to the polyphenols, gramine increased its toxic action over time,
      independent of the prevailing pH. All exposures caused slight to severe lipid
      peroxidation (LPO) in the phototrophs. Hence, one mechanism of growth inhibition
      may be oxidative stress-mediated reduction in photosynthesis. The presented
      results suggest that in successful field trials with leachate, the prevailing
      environmental conditions may inactivate polyphenols and xenobiotics other than
      polyphenols may be more effective. 

PMID- 24332730
TI  - Microbial-electrochemical bioremediation and detoxification of dibenzothiophene
      polluted soil.
AB  - Bioremediation is a relatively efficient and cost-effective technology for
      treating polluted soils. However, the availability of suitable electron acceptors
      to sustain microbial respiration can reduce the microbial activity. This work
      aims to evaluate the impact of burying electrically conductive electron acceptors
      in soil for enhancing the removal of dibenzothiophene (DBT) by native
      electrogenic microbes. Although this novel approach is based on the use of a
      microbial electrochemical technology as microbial fuel cells, our goal is not to
      harvest energy but to maximize bioremediation, so we concluded to name the device
      as Microbial Electroremediating Cell (MERC). Our results proved that stimulating
      the microbial electrogenic metabolism, DBT removal was enhanced by more than 3
      fold compared to the natural attenuation. On top of that, ecotoxicological test
      using green algae confirms a decrease of 50% in the toxicity of the treated soil
      during incubation in MERC, in contrast to the unaltered values detected under
      natural conditions. 

PMID- 24332731
TI  - Effects of fluoride on bacterial growth and its gene/protein expression.
AB  - To determine the effects of fluoride on bacterial growth, as well as upon its
      gene/protein expression, we grew Escherichia coli expressing GFPuv (E. coli
      GFPuv) in Luria Bertani medium at different concentrations of NaF, 0, 0.1 mM, 1
      mM, 10 mM and 100 mM. Results showed that E. coli-pGFPuv growth and expression of
      mRNA and protein of GFPuv were increased at 0.1 and 1 mM, but were inhibited at
      10 and 100 mM, which demonstrated that fluoride has a classic rise/fall response
      of inducing E. coli-GFPuv growth and gene and protein expression of GFPuv at 1
      mM. Our observation suggests that the effect of fluoride on bacterial growth may
      be from regulation of mRNA expression.

PMID- 24332732
TI  - An overview of the role of goethite surfaces in the environment.
AB  - Goethite, one of the most thermodynamically stable iron oxides, has been
      extensively researched especially the structure (including surface structure),
      the adsorption capacity to anions, organic/organic acid (especially for the soil
      organic carbon) and cations in the natural environment and its potential
      application in environmental protection. For example, the adsorption of heavy
      metals by goethite can decrease the concentration of heavy metals in aqueous
      solution and immobilize; the adsorption to soil organic carbon can decrease the
      release of carbon and fix carbon. In this present overview, the possible
      physicochemical properties of the goethite surface contributing to the strong
      affinity of goethite to nutrients and contaminants in natural environment are
      reported. Moreover, these chemicals adsorbed by goethite were also summarized and
      the suggested adsorption mechanism for these adsorbates was elucidated, which
      will help us understand the role of goethite in natural environment and provide
      some information about goethite as an absorbent. In addition, the feasibility of
      goethite used as catalyst carrier and the precursor of NZVI was proposed for
      removal of environmental pollution. 

PMID- 24332733
TI  - Vortex-assisted low density solvent based demulsified dispersive liquid-liquid
      microextraction and high-performance liquid chromatography for the determination
      of organophosphorus pesticides in water samples.
AB  - A simple, rapid, effective and eco-friendly preconcentration method, vortex
      assisted low density solvent based solvent demulsified dispersive liquid-liquid
      microextraction (VLDS-SD-DLLME), followed by high performance liquid
      chromatography-diode array detector (HPLC-DAD) analysis, has been developed for
      the first time for the determination of four organophosphorus pesticides (OPPs)
      (e.g., azinphos-methyl, parathion-methyl, fenitrothion and diazinon) in
      environmental water samples. In this preconcentration procedure, an emulsion was
      obtained after the mixture of extraction solvent (1-dodecanol) and dispersive
      solvent (acetonitrile, ACN) was injected rapidly into 10 mL of the sample
      solution. The vortex agitator aided the dispersion of the extraction solvent into
      the sample solution. After the formation of an emulsion, the demulsifier (ACN)
      was added, resulting in the rapid separation of the mixture into two phases
      without centrifugation. Under optimal conditions, the proposed method provided
      high extraction efficiency (90-99%), good linearity range (0.5-500 ng mL(-1)),
      low limits of detection (0.25-1 ng mL(-1)) and good repeatability and recoveries
      were obtained.

PMID- 24332734
TI  - Catalytic oxidation of Hg(0) by MnOx-CeO2/gamma-Al2O3 catalyst at low
      temperatures.
AB  - MnOx-CeO2/gamma-Al2O3 (MnCe) selective catalytic reduction (SCR) catalysts
      prepared by sol-gel method were employed for low-temperature Hg(0) oxidation on a
      fixed-bed experimental setup. BET, XRD and XPS were used to characterize the
      catalysts. MnCe catalysts exhibited high Hg(0) oxidation activity at low
      temperatures (100-250  degrees C) under the simulated flue gas (O2, CO2, NO, SO2,
      HCl, H2O and balanced with N2). Only a small decrease in mercury oxidation was
      observed in the presence of 1200 ppm SO2, which proved that the addition of Ce
      helped resist SO2 poisoning. An enhancing effect of NO was observed due to the
      formation of multi-activity NOx species. The presence of HCl alone had excellent
      Hg(0) oxidation ability, while 10 ppm HCl plus 5% O2 further increased Hg(0)
      oxidation efficiency to 100%. Hg(0) oxidation on the MnCe catalyst surface
      followed the Langmiur-Hinshelwood mechanism, where reactions took place between
      the adsorbed active species and adsorbed Hg(0) to form Hg(2+). NH3 competed with
      Hg(0) for active sites on the catalyst surface, hence inhibiting Hg(0) oxidation.
      This study shows the feasibility of a single-step process integrating low
      temperature SCR and Hg(0) oxidation from the coal combustion flue gas.

PMID- 24332735
TI  - Bioremediation of fipronil by a Bacillus firmus isolate from soil.
AB  - Persistence of fipronil, a new molecule in extensive use against various insect
      pests is causing serious problems to the environment. Bacillus firmus was
      isolated by selective enrichment from soil samples collected from sugar fields
      with known history of pesticide usage and evaluated for metabolization of
      fipronil in clay loam soil. Soil samples in 50 g aliquotes were fortified with
      fipronil @ 0.50-1.50 mg kg(-1) and inoculated with B. firmus cells (45*10(7) CFU
      mL(-1)) and incubated at 25  degrees C. Each sample in triplicates was drawn
      periodically up to 56 d and residual fipronil contents analyzed by gas liquid
      chromatograph. Fipronil residues were not detected after 35 d at lower doses of
      fipronil (@ 0.50, 0.75 and 1.00 mg kg(-1)). However, at higher doses (@ 1.25 and
      1.50 mg kg(-1)) than this total metabolization of fipronil could be observed
      after 35 and 42 d, respectively. Thus whereas, B. firmus proved its potential in
      efficient metabolization of fipronil, the period required for the same was dose
      dependent. Amongst various metabolites of fipronil degradation, fipronil sulfide
      was found to be the main metabolite followed by fipronil sulfone and fipronil
      amide. Though, desulfinyl metabolite earlier reported as one of the main
      metabolite of fipronil degradation, the existence of the same was not detected in
      any of the treatment.

PMID- 24332736
TI  - Effect of colostrum redox balance on the oxidative status of calves during the
      first 3 months of life and the relationship with passive immune acquisition.
AB  - New-born calves depend upon colostrum intake for the acquisition of
      immunoglobulins (Ig) and other beneficial substances. However, colostrum is also
      a source of reactive oxygen species (ROS). Intrinsic production of ROS also
      increases after birth, so the combination of colostral and intrinsic ROS could
      overwhelm the antioxidant capacity of the calf leading to oxidative stress (OS),
      a condition that has been shown to play a key role in the initiation and
      development of several pathological conditions. The aim of this observational
      study was to assess the effects of the redox balance of colostrum on the
      oxidative status of calves and on passive immune transfer. Serum samples were
      taken from 20 calves on their day of birth, every week during their first month
      of life and at 2 and 3 months of age, and the concentrations of ROS and serum
      antioxidant capacity (SAC) assayed. The oxidative/anti-oxidative profile and IgG
      content of the colostrum were also assessed. The redox balance of the colostrum
      had a significant effect on both calf oxidative status and on passive immune
      transfer (as measured by calf serum IgG concentration), which indicates that the
      oxidative/antioxidative profile of colostrum should be measured when colostrum
      quality is assessed. The highest risk of OS during the study period was found to
      be when the calves were fed artificial milk replacer; this suggests that calves
      should be supplemented with antioxidants during this period in order to minimize
      any harmful consequences of high ROS generation.

PMID- 24332737
TI  - [Necrotizing fasciitis and double bowel perforation after retropubic sub-urethral
      sling].
AB  - A 60-year-old woman without medical history developed after a Tension-free
      Vaginal Tape (TVT) procedure a necrotizing fasciitis and an abscess. After
      unadapted initial treatment, surgical procedure revealed 2 bowel perforations
      caused by the sling. Treatment was achieved by total mesh removal, bowel repair,
      necrosis excision and vacuum-assisted closure system. This is the first case
      report about the association of necrotizing fasciitis and double bowel
      perforations after TVT procedure. Any critical sepsis or with unsatisfactory
      evolution after retropubic sub-urethral sling has to make look for a digestive
      wound.

PMID- 24332738
TI  - [Cervical Pap smear in an epidemiologically exposed population: ideas, facts and
      arguments].
AB  - OBJECTIVES: To analyse the prevalence of abnormal papsmears in a primary care
      center and the screening practices. MATERIALS AND METHODS: Single-center
      retrospective study on 1,430 FCU performed in 1,251 patients between January 2009
      and December 2011 with analysis of demographic, clinical and epidemiological
      chararacteristics of the women, and the monitoring of the patients with
      pathological papsmears. RESULTS: The study population was predominantly young
      (under 25), unmarried, nulliparous, and using contraception. Among the 1,244 FCU,
      nearly 90% of them were interpretable with the junction area interested. Nine
      percent were pathological with mainly ASC-US and L-SIL (3.5% and 4.5%) with no
      difference between more and less than 25years. Two factors were significantly
      associated with the presence of pathological papsmear: first intercourse before
      age 14 and smoking more than 10 cigarettes per day. Monitoring of patients with a
      pathological papsmear showed that 33% of patients had not an appropriate follow
      up especially younger patients. DISCUSSION: To perform papsmear before 25 years
      because the patient has associated high risk HPV co-factors does not appear
      justified by the severity or frequency of cytological lesions, especially as it
      increases the financial cost and is responsible of potential deleterious actions
      such as conizations probably excessive among the youngest patients. Personalized
      monitoring of these patients with a pathological papsmear is required. The French
      practice recommendations on cervical cancer screening (first screening at age 25,
      26 years cytological control then every 3 years up to 65 years in patients who
      have or have had sex) deserve to be applied in young and disadvantaged patients.

PMID- 24332739
TI  - [Prevention of obstetrical complications following LEEP, is it possible?].
AB  - Recent epidemiological data suggest an increase of the incidence and prevalence
      of CIN as well as a decrease of the mean age of the patients presenting these
      lesions. Large loop electrosurgical procedure (LEEP) is the most commonly used
      treatment method. According to recent studies LEEP provides a 1.4 to 7.0 fold
      increase of preterm delivery. Cervical cerclage does not show efficiency in
      reducing this risk, even if cervical shortening is measured by transvaginal
      ultrasound. Considering histological severity of lesions and the age of patients,
      number of currently conducted conizations in France could be avoided and so their
      obstetrical consequences prevented, just because no treatment is necessary or
      could be done by ablative procedures. 

PMID- 24332740
TI  - [Stage IV uterine prolapse and pregnancy: a case report].

PMID- 24332741
TI  - [Risk factors associated with spontaneous preterm deliveries before 30 weeks in
      Martinique F.W.I.: a case-control study].
AB  - OBJECTIVES: Early premature delivery is more prevalent in overseas territories
      than in continental France. Many differences are observed between pregnant women
      in France and in Martinique which may explain the higher preterm birth rate in
      the latter territory. The study compares prevalence of possible risk factors in
      preterm and term deliveries in Martinique. PATIENTS AND METHODS: A retrospective
      study was conducted during two years (2010-2011). All deliveries before 30 weeks
      were included and several characteristics were compared with a group of term
      deliveries during the same period. All premature deliveries before 30 weeks were
      collected but only spontaneous ones were analysed. RESULTS: Fifty deliveries
      before 30 weeks were recorded, among which 38 were spontaneous. Only a
      significantly higher prevalence of previous preterm delivery (OR=4.1 [1.3-13])
      and twin pregnancies (OR=26.6 [3.19-219.6]) was found in the study group. Gram
      negative bacterial species were also more prevalent in vaginal sampling of
      preterm deliveries (OR=23.3 [2.7-204.6]). CONCLUSION: Factors linked to
      prematurity before 30 weeks in Martinique are classical. Several features are
      different between pregnant women in France and in Martinique but do not appear as
      risk factors for prematurity in the latter territory.

PMID- 24332742
TI  - [Aberrant right subclavian artery (arteria lusoria) and the risk for trisomy 21.
      Retrospective study of 11,479 fetopathological examinations].
AB  - OBJECTIVE: The aberrant right subclavian artery is a malformation of the aortic
      arch present at less than 2 % of the individuals in the general population. This
      incidence is higher in trisomy 21, making it possible use the aberrant right
      subclavian artery as a prenatal marker of trisomy 21. MATERIAL AND METHODS: This
      work, which relates to a series of 11,479 consecutive fetal autopsies aims to
      measure the force of association between the aberrant right subclavian artery and
      trisomy 21, to confront our results with the sonographic series previously
      published and to contribute to assess the place that can have this sign in the
      echographic screening and the fetopathologic diagnosis of trisomy 21. RESULTS:
      The isolated presence of an aberrant right subclavian artery does not represent
      an argument sufficient for the indication of a karyotype. But the detection of
      this anomaly must make pay a special attention in search of other associated
      signs. CONCLUSION: On the results of this study, the aberrant right subclavian
      artery has to be considered as a part of the spectrum not only of trisomy 21, but
      also of many other congenital syndromes.

PMID- 24332743
TI  - [Current and future use of surgical skills simulation in gynecologic resident
      education: a French national survey].
AB  - OBJECTIVES: Simulation is a promising method to enhance surgical education in
      gynecology. The purpose of this study was to provide baseline information on the
      current use of simulators across French academic schools. MATERIALS AND METHODS:
      Two questionnaires were created, one specifically for residents and one for
      professors. Main issues included the type of simulators used and the kind of use
      made for training purposes. Opinions and agreement about the use of simulators
      were also asked. RESULTS: Twenty-six percent of residents (258/998) and 24% of
      professors (29/122) answered the questionnaire. Sixty-five percent of residents
      (167/258) had experienced simulators. Laparoscopic pelvic-trainers (84%) and
      sessions on alive pigs (63%) were most commonly used. Residents reported access
      to simulators most commonly during introductory sessions (51%) and days of
      academic workshops (38%). Residents believed simulators very useful for training.
      Professors agreed that simulators should become a required part of residency
      training, but were less enthusiastic regarding simulation becoming a part of
      certification for practice. CONCLUSION: Surgical skills simulators are already
      experienced by a majority of French gynecologic residents. However, the use of
      these educational tools varies among surgical schools and remains occasional for
      the majority of residents. There was a strong agreement that simulation
      technology should be a component of training.

PMID- 24332744
TI  - The effects of surgical lengthening of hamstring muscles in children with
      cerebral palsy--the consequences of pre-operative muscle length measurement.
AB  - Children with cerebral palsy often undergo multiple orthopaedic surgical
      procedures in a single episode. Evidence of the effectiveness of individual
      components within the overall package is sparse. The introduction of
      musculoskeletal modelling in Oswestry has led to a more conservative management
      approach being taken with hamstring muscles for children walking in a degree of
      crouch. Muscles which were shown to be of at least normal length at initial
      contact were not surgically lengthened, as would have been the case previously. A
      retrospective review of 30 such patients was therefore possible, comparing 15
      patients treated before the policy change who had their hamstrings lengthened
      with 15 treated after who did not. All patients had pre and post operative gait
      assessments and significant changes were observed for each group separately and
      for the two groups when compared. The comparison revealed that preserving the
      hamstrings does tend to reduce, and therefore normalize, the dynamic muscle
      length. Examination of the two patient groups separately, however, reveals a more
      complex picture with more global gait improvements seen when the hamstrings were
      lengthened. No absolute recommendation can be made to inform the clinical
      management of all children with normal to long hamstring muscles during gait. The
      final decision of whether to include a hamstring lengthening will need to take
      into account the characteristics of the individual child. 

PMID- 24332745
TI  - Changes in out-of-pocket payments for contraception by privately insured women
      during implementation of the federal contraceptive coverage requirement.
AB  - BACKGROUND: As part of the Affordable Care Act, a federal requirement for private
      health plans to cover contraceptive methods, services and counseling, without any
      out-of-pocket costs to patients, took effect for millions of Americans in January
      2013. STUDY DESIGN: Data for this study come from a subset of the 3207 women aged
      18-39 years who responded to two waves of a national longitudinal survey. This
      analysis focused on the 889 women who were using hormonal contraceptive methods
      in both the fall 2012 and spring 2013 waves and the 343 women who used the
      intrauterine device at either wave. Women were asked about the amount they paid
      out of pocket in an average month for their method of choice. RESULTS: Between
      Wave 1 and Wave 2, the proportion of privately insured women paying zero dollars
      out of pocket for oral contraceptives increased substantially, from 15% to 40%;
      by contrast, there was no significant change among publicly insured or uninsured
      women (whose coverage was not affected by the new federal requirement). Similar
      changes were seen among privately insured women using the vaginal ring.
      CONCLUSIONS: The initial implementation of the federal contraceptive coverage
      requirement appears to have had a notable impact on the out-of-pocket costs paid
      by privately insured women. Additional progress is likely as the requirement
      phases in to apply to more private plans, but with evidence that not all methods
      are being treated equally, policymakers should consider stepped-up oversight and
      enforcement of the provision. IMPLICATIONS: This study measures the out-of-pocket
      costs for women with private, public and no insurance prior to the federal
      contraceptive coverage requirement and after it took effect; in doing so, it
      highlights areas of progress in eliminating these costs and areas that need
      further progress.

PMID- 24332746
TI  - Medical termination of pregnancy during the second versus the first trimester and
      its effects on subsequent pregnancy.
AB  - OBJECTIVE: The objective was to compare the risks of preterm birth, low birth
      weight, small for gestational age (SGA) infants and placental complications in
      subsequent pregnancy after second vs. first trimester medical termination of
      pregnancy (MTOP) in primigravid women. STUDY DESIGN: A total of 88,522 women who
      underwent termination of pregnancy during 2000-2009 were identified using Finnish
      health registers. Of them, primigravid women who underwent MTOP and had
      subsequent pregnancy ending in live birth up to the end of 2009 (n=3843) were
      included in the study. The incidences and risks of preterm birth, low birth
      weight, SGA infants and placental complications after first- (n=3427) vs. second
      trimester MTOP (n=416) were compared. RESULTS: Differences between the study
      groups in the incidences of preterm birth (3.9% in both groups), low birth weight
      (3.9% in the second- vs. 3.2% in the first-trimester group), SGA infants (2.4%
      vs. 2.5%) and placental complications (1.9% vs. 2.6%) were statistically
      insignificant. Second-trimester MTOP was associated with similar risks of preterm
      birth, low birth weight, SGA infants and placental complications compared with
      first-trimester MTOP after adjustment for background characteristics. After
      second-trimester MTOP, 51.2% of women underwent surgical evacuation, and 4.3%
      were diagnosed with infection. The differences in the risks of preterm birth, low
      birth weight, SGA infants and placental complications were statistically
      insignificant between women with vs. without these complications following second
      trimester MTOP. CONCLUSIONS: Second-trimester MTOP among primigravid women did
      not increase the risks of preterm birth, low birth weight, SGA infants or
      placental complications in subsequent pregnancy compared with first-trimester
      MTOP. IMPLICATIONS: The present study suggests that medical termination of
      pregnancy in primigravid women during second vs. first trimester does not
      increase the risks of adverse outcomes in subsequent pregnancy and delivery. The
      data are of value when counseling women undergoing second-trimester TOP.

PMID- 24332747
TI  - J wave elevation to monitor quinidine efficacy in early repolarization syndrome.
AB  - We present the case of a 14-year-old female with early repolarization syndrome
      who presented with recurrent ventricular fibrillation and ICD shocks which were
      refractory to multiple drugs and catheter ablation. Treatment with quinidine, an
      Ito blocker, resulted in a normalization of J waves and suppression of VF.
      Interestingly, J wave amplitude correlated with the ventricular arrhythmia
      susceptibility and quinidine levels. The case highlights the importance of
      quinidine for management of ventricular arrhythmias in the context of early
      repolarisation and suggests that J wave amplitude may be an important indicator
      of therapeutic drug levels and arrhythmia susceptibility. 

PMID- 24332748
TI  - A study of metastatic carcinoma found in hernia sacs between 2006 and 2012 at one
      institution.
AB  - Hernia sacs are generally regarded as routine specimens in the daily practice of
      surgical pathology. However, unexpected findings including carcinoma can
      occasionally arise in these seemingly benign specimens. To ascertain the
      prevalence of metastatic carcinoma found within hernia sacs and to determine the
      importance of routine histologic examination of hernia sacs, we conducted a
      retrospective study of all hernia sacs with a diagnosis of metastatic carcinoma
      reported in our hospital system between January 2006 and December 2012. Of 3117
      total herniorrhaphy specimens between 2006 and 2012, 11 (0.35%) were found to
      have metastatic carcinoma. Interestingly, in 3 cases, the initial diagnosis of
      cancer was made during histologic examination of the hernia sac. Metastatic
      carcinoma in hernia sacs is a rare occurrence; however, it is encountered in
      routine practice. It is recommended that herniorrhaphy specimens not be discarded
      and, instead, be regarded as peritoneal biopsies for routine histologic
      examination. 

PMID- 24332749
TI  - Expression profile of endothelin 1 and its receptor endothelin receptor A in
      papillary thyroid carcinoma and their correlations with clinicopathologic
      characteristics.
AB  - The endothelin axis is a group of signaling molecules and their receptors that
      have been implicated in vascularization of cancers, with their expression being
      observed to change in different cancer types. In this research, we examined the
      expression of endothelin 1 and endothelin receptor A at the protein and messenger
      RNA (mRNA) levels in 123 papillary thyroid carcinomas and 40 matched lymph nodes
      with metastatic papillary thyroid carcinomas. We found altered endothelin axis
      mRNA expression in several clinicopathologic parameters with increased endothelin
      1 expression in thyroid papillary carcinoma showing stromal calcification,
      cancers in men, and primary cancers with lymph node metastases. Increased
      endothelin receptor A mRNA expression was noted in the larger cancers. There is a
      significant correlation between expression of endothelin receptor A and
      endothelin 1 in papillary thyroid carcinoma. Both endothelin receptor A and
      endothelin 1 mRNA expressions were significantly higher in metastatic carcinoma
      in the lymph node than in primary thyroid cancer. The metastatic carcinoma in the
      lymph node had increased expression compared with matched primary thyroid
      carcinoma. Expressions of endothelin 1 and endothelin receptor A were also
      documented as being high at the protein level. Our results indicate that in
      thyroid cancer, endothelin 1 and endothelin receptor A are associated with growth
      in advanced stages and lymph node metastases, likely through known angiogenic
      linkages. Targeting the endothelin axis may be useful in planning angiogenesis
      therapy for thyroid cancer. 

PMID- 24332750
TI  - Determinants of pain perception after external cephalic version in pregnant
      women.
AB  - OBJECTIVE: A considerable proportion of pregnant women with a fetus in breech
      position refuses external cephalic version (ECV), with fear of pain as important
      barrier. As a consequence, they are at high risk for caesarean section at term.
      The current study investigated determinants of pain perception during ECV, with
      special attention to maternal mental state such as depression and fear of ECV.
      DESIGN: Prospective study of 249 third-trimester pregnant women with breech
      position with a request for an ECV attempt. SETTING: Department of Obstetrics and
      Gynaecology in a large teaching hospital in the Netherlands. METHODS: Prior to
      the ECV attempts, obstetric factors were registered, participants fulfilled the
      Edinburgh Depression Scale (EDS) and reported fear of ECV on a 10-point visual
      analog scale. Perception of pain intensity was measured with a 10-point visual
      analog scale, immediately after ECV. FINDINGS: Multivariate linear regression
      analyses showed success of ECV to be the strongest predictor of pain perception.
      Furthermore, scores on the depression questionnaire and degree of fear of ECV
      independently explained pain perception, which was not the case for obstetrical
      or ECV related factors. CONCLUSION: Apart from ECV outcome, psychological factors
      like depression and fear of ECV were independently related to pain perception of
      an ECV attempt. IMPLICATION FOR PRACTICE: Maternal mood state should be taken
      into account when offering an ECV attempt to women with a fetus in breech
      position. Due to the painful experience and the importance of successful outcome,
      ECV should only be attempted in institutions with experienced practitioners and
      with careful attention to maternal mood and the way a woman is coping with the
      ECV attempt.

PMID- 24332751
TI  - Making sense of the situation: women's reflection of positive fetal screening 11
      21 months after giving birth.
AB  - OBJECTIVE: we aimed to gain insights into women's reflection on their experience
      of receiving a false-positive screening result for fetal anomalies, more than 11
      months from birth. DESIGN AND SETTING: the women constituted a subgroup of
      participants in a larger cohort study (n=1111) where the purpose was to explore
      women's experience of maternity services, their health, well-being, attitudes and
      expectations during pregnancy and after birth. Semi-structured interviews were
      collected from 14 women 11-21 months after birth who had been screened positive
      for fetal chromosomal abnormality in early pregnancy. The method of life-world
      phenomenological approach was used in data collection and analyses. FINDING: four
      themes were identified: first reaction, framing of the news, I am not an island
      and pregnancy lost and regained. With few exceptions, their experience can be
      seen as a pathway from shock to balanced feeling where women have made sense of
      what happened and have dealt adequately with their situation. CONCLUSION: this
      study indicates that few women still experience anxiety and concerns in relation
      to positive fetal screening result more than 11 months from birth. They however
      remember vividly their first reaction and how the result was presented. As such,
      the findings have implications in the clinical context meaning that framing of
      the news on face-to-face level, extended information about the test results, help
      to sort out mixed feelings and support from a named midwife are of importance.

PMID- 24332752
TI  - Profiling the time-course changes in neuromuscular function and muscle damage
      over two consecutive tournament stages in elite rugby sevens players.
AB  - OBJECTIVES: Many International Rugby Board (IRB) sevens competitions require that
      two tournament stages are played over consecutive weekends, but the impact this
      has on player physical performance and recovery is lacking. We examined the
      influence of two consecutive tournaments on neuromuscular function (NMF) and
      muscle damage in rugby sevens players. DESIGN: Ten elite international rugby
      sevens players completed this observational study over 2 tournaments, separated
      by 5 days, during the IRB sevens series. METHODS: On the morning of day 1 and 2,
      of both tournament 1 (T1) and 2 (T2), players performed countermovement jumps
      (CMJ; jump height [JH]) and capillary blood samples (creatine kinase [CK]) were
      collected. After the last match of each day, further capillary samples were
      collected. Additional, CMJ were performed 12 and 60 h post-T1. RESULTS: Player JH
      decreased from day 1 to day 2 during T1 (mean +/- SD; -6.0 +/- 5.4%; P=0.016),
      was reduced at 12 (-26.1 +/- 5.0%; P<0.001) and 60 h post-T1 (-7.1 +/- 4.8%;
      P=0.003) and remained lower, at am day 1 of T2 (-8.0 +/- 6.0%; P=0.007), when
      compared with day 1 of T1. Player JH was lower on day 1 and 2 of T2, compared
      with T1 (P<0.05). CK concentrations were greater than baseline at all time points
      during each tournament (P<0.001); no between tournament differences in CK
      responses existed (P=0.302). CONCLUSIONS: A single sevens tournament reduces NMF
      such that players are not fully recovered by the start of the second competition
      stage, however CK returns to baseline in-between and shows the same pattern
      across two consecutive tournaments.

PMID- 24332753
TI  - Who is the right patient for TAVI?
AB  - Transcatheter aortic valve implantation (TAVI) has rapidly emerged as a valid
      therapeutic option for patients with severe symptomatic aortic stenosis who are
      high risk or ineligible for conventional surgical aortic valve replacement.
      Despite its minimally invasive nature, TAVI is invariably associated with
      complications in these old patients that may affect outcomes. Although the
      success of TAVI is determined by multiple factors, good screening and appropriate
      patient selection is crucial. Selection of the right patient includes the
      determination of risk levels and feasibility of a safe procedure in each
      individual case. Here, we describe below our critical appraisal of patient
      selection for TAVI. 

PMID- 24332755
TI  - Prostaglandin treatment at the onset of norgestomet and estradiol-based
      synchronization protocols did not alter the ovarian follicular dynamics or
      pregnancy per timed artificial insemination in cyclic Bos indicus heifers.
AB  - The aim of the present study was to evaluate the effects of the PGF2alpha
      treatment given at the onset of a synchronization of ovulation protocol using a
      norgestomet (NORG) ear implant on ovarian follicular dynamics (Experiment 1) and
      pregnancy per AI (P/AI; Experiment 2) in cyclic (CL present) Bos indicus heifers.
      In Experiment 1, a total of 46 heifers were presynchronized using two consecutive
      doses of PGF2alpha 12 days apart. At first day of the synchronization protocol
      the heifers received implants containing 3mg of NORG and 2 mg of estradiol
      benzoate (EB). At the same time, heifers were randomly assigned to receive 150 mg
      of D-cloprostenol (n=23; PGF2alpha) or no additional treatment (n=23; Control).
      When the ear implants were removed 8 days later, all heifers received a PGF2alpha
      treatment and 1 mg of EB was given 24 h later. The follicular diameter and
      interval to ovulation were determined by transrectal ultrasonography. No effects
      of PGF2alpha treatment on the diameter of the largest follicle present were
      observed at implant removal (PGF2alpha=9.8+/-0.4 vs. Control=10.0+/-0.3 mm;
      P=0.73) or after 24 h (PGF2alpha=11.1+/-0.4 vs. Control=11.0+/-0.4 mm; P=0.83).
      No differences in the time of ovulation after ear implant removal
      (PGF2alpha=70.8+/-1.2 vs. Control=73.3+/-0.9 h; P=0.10) or in the ovulation rate
      (PGF2alpha=87.0 vs. Control=82.6%; P=0.64) between treatments were observed. In
      Experiment 2, 280 cyclic heifers were synchronized using the same experimental
      design described above (PGF2alpha; n=143 and Control; n=137), at random day of
      the estrous cycle. All heifers received 300 IU of equine chorionic gonadotropin
      (eCG) and 0.5 mg of estradiol cypionate (as ovulatory stimulus) when the NORG ear
      implants were removed. Timed artificial insemination (TAI) was performed 48 h
      after implant removal and the pregnancy diagnosis was conducted 30 days later. No
      effects on the P/AI due to PGF2alpha treatment were observed (PGF2alpha=51.7 vs.
      Control=57.7%; P=0.29). In conclusion, PGF2alpha treatment at the onset of NORG
      based protocols for the synchronization of ovulation did not alter the ovarian
      follicular responses or the P/AI in cyclic Bos indicus beef heifers synchronized
      for TAI.

PMID- 24332756
TI  - Bioremediation and fodder potentials of two Sargassum spp. in coastal waters of
      Shenzhen, South China.
AB  - In this study, the bioremediation potentials of two seaweeds (Sargassum
      hemiphyllum and S. henslowianum) against pollution in a coastal mariculture area
      of Shenzhen, South China, were investigated by comparing the growth, nutrient
      bioaccumulation capacity of plants from the seaweed bed (control site) with
      plants from the fish farm. Results indicated that both species are potential
      candidates for bioremediation in the fish farm areas in terms of their high
      growth rates and high bioaccumulation capacities on inorganic nutrients. Both
      Sargassum spp. contain high levels of crude protein (11.7-14.0%) and crude fat
      (2.2-2.7%), suggesting high nutritional values. The S. hemiphyllum may serve as a
      good aquaculture fodder with high nutritional compositions and low heavy metal
      contents. However, heavy metals (Cr, Pb and Cd) of S. henslowianum exceed the
      maximum allowable concentrations as aquatic feed, which restricts its fodder
      application. In general, the results of this study may contribute to the marine
      pollution bioremediation in the coastal areas of South China, especially in
      mariculture zones. 

PMID- 24332757
TI  - Detection of Helicobacter pylori in the coastal waters of Georgia, Puerto Rico
      and Trinidad.
AB  - Fecal pollution in the coastal marine environments was assessed at eleven
      sampling locations along the Georgia coast and Trinidad, and nine sites from
      Puerto-Rico. Membrane filtration (EPA method 1604 and method 1600) was utilized
      for Escherichia coli and enterococci enumeration at each location. Quantitative
      polymerase chain reaction (qPCR) amplification of the 16S ribosomal RNA gene was
      used to determine the presence of the Helicobacter pylori in marine samples.
      There was no significant correlation between the levels of E. coli, enterococci
      and H. pylori in these water samples. H. pylori was detected at four of the 31
      locations sampled; Oak Grove Island and Village Creek Landing in Georgia, Maracas
      river in Trinidad, and Ceiba Creek in Puerto Rico. The study confirms the
      potential public health risk to humans due to the widespread distribution of H.
      pylori in subtropical and tropical costal marine waters. 

PMID- 24332754
TI  - Long-chain Acyl-CoA synthetase 4A regulates Smad activity and dorsoventral
      patterning in the zebrafish embryo.
AB  - Long-chain polyunsaturated fatty acids (LC-PUFA) and their metabolites are
      critical players in cell biology and embryonic development. Here we show that
      long-chain acyl-CoA synthetase 4a (Acsl4a), an LC-PUFA activating enzyme, is
      essential for proper patterning of the zebrafish dorsoventral axis. Loss of
      Acsl4a results in dorsalized embryos due to attenuated bone morphogenetic protein
      (Bmp) signaling. We demonstrate that Acsl4a modulates the activity of Smad
      transcription factors, the downstream mediators of Bmp signaling. Acsl4a promotes
      the inhibition of p38 mitogen-activated protein kinase and the Akt-mediated
      inhibition of glycogen synthase kinase 3, critical inhibitors of Smad activity.
      Consequently, introduction of a constitutively active Akt can rescue the
      dorsalized phenotype of Acsl4a-deficient embryos. Our results reveal a critical
      role for Acsl4a in modulating Bmp-Smad activity and provide a potential avenue
      for LC-PUFAs to influence a variety of developmental processes. 

PMID- 24332758
TI  - [A comparative study between two procedures of TVT retropubic mid-urethral sling
      placement for treatment of female stress urinary incontinence].
AB  - OBJECTIVE: To evaluate complications and functional outcomes at 1 year and more
      of a modified Tension-free Vaginal Tape (TVT) technique from that of classic TVT.
      PATIENTS AND METHODS: Retrospective study comparing the two techniques. For the
      modified TVT technique, a peri-urethrovesical hydrodissection was performed. An
      18-gauge hollow needle, in which a thread was introduced, was used as an
      ancillary for the placement of the sling. The sling was secured to the thread and
      then positioned with it. Bladder filling objectified perforations. An absorbable
      suture around the sling allowed its descent if necessary. RESULTS: One hundred
      and eighteen procedures were performed (54 classic TVT and 64 modified TVT). For
      the standard TVT and the modified TVT, the vesico-urethral perforation rates were
      respectively 7.4% and 1.5% (P<0.05), those of reoperations for pulling the sling
      downward 11.1% and 1.5% (P<0.05). A 1 year and more, healing and satisfaction
      rates were respectively 83.3% and 79.2% for the standard TVT versus 88.2% and 90%
      for the modified TVT (NS). The dissatisfaction rate was lower for the modified
      TVT (P<0.05). CONCLUSION: By modifying the placement of the classic TVT, it is
      possible to reduce its complications while maintaining its efficacy.

PMID- 24332759
TI  - Naming a novel hemoglobin variant.

PMID- 24332760
TI  - Mefloquine restrictions, anti-malarial drug safety and the new Italian
      recommendations for malaria prophylaxis.

PMID- 24332761
TI  - Neurological manifestations of dengue: a cross sectional study.
AB  - BACKGROUND: Dengue is an infectious disease caused by a virus of the flaviviridae
      family. It is a multi systemic illness causing considerable morbidity and
      mortality. A spectrum of neurological manifestations has been associated with
      dengue. METHODS: This was a descriptive cross sectional study including patients
      diagnosed with Dengue fever (DF), Dengue with warning signs and severe dengue
      with neurological sequale presenting to the Institute of Neurology, National
      Hospital of Sri Lanka from June 2011 to August 2012. All patients underwent
      serology testing for Dengue IgM in blood and CSF as confirmation of the
      diagnosis. RESULTS: Seven patients were included. 1/7 had bilateral optic
      neuritis (ON), 3/7 had a cerebellar syndrome (CS), 2/7 had transverse myelitis
      (TM) and 1/7 had cranial nerve palsy. The patient with ON had a post-infectious
      pattern and protracted recovery. All patients with CS had bilateral involvement.
      All had a self limiting course with complete recovery. Two were associated with
      acute infection. Both patients with TM had longitudinally extensive disease with
      one patient experiencing complete recovery. The patient with cranial nerve
      involvement had isolated 6th nerve palsy. CONCLUSIONS: Neurological
      manifestations of dengue are diverse. It is important to consider dengue as a
      cause for the above neurological presentations in hyper endemic territories for
      the disease.

PMID- 24332762
TI  - Renal replacement therapy due to type 1 diabetes; time trends during 1995-2010--a
      Swedish population based register study.
AB  - BACKGROUND: End stage renal disease (ESRD), is the most severe complication of
      diabetes mellitus. This population-based study analysed time trends for start of
      renal replacement therapy (RRT) due to type 1 diabetes compared to type 2
      diabetes and other diagnoses. MATERIAL AND METHODS: We used data on patients who
      were registered 1995-2010 in the Swedish Renal Registry, a nationwide register
      covering 95 % of all patients with uraemia. The patients were analysed according
      to their original kidney disease. The incidence was analysed by calendar year,
      age at start of RRT and gender. RESULTS: Of 17389 patients who were registered,
      1833 had type 1 diabetes; 65% were men. The mean age at onset of RRT for patients
      with type 1 diabetes was 52.8 years which increased by more than 3 years over the
      studied period. The number of patients in need of RRT due to type 1 diabetes
      decreased, while RRT due to type 2 diabetes increased during the period studied.
      CONCLUSIONS: The overall incidence of RRT in Sweden is rather constant over the
      years but the need for RRT in type 1 diabetes patients decreased and patients
      with type 1 diabetes tend to become older at onset of RRT.

PMID- 24332763
TI  - Visit-to-visit variability in systolic blood pressure predicts development and
      progression of diabetic nephropathy, but not retinopathy, in patients with type 2
      diabetes.
AB  - OBJECTIVE: To investigate whether visit-to-visit variability in systolic blood
      pressure (SBP) can predict development and progression of diabetic nephropathy
      and retinopathy in patients with type 2 diabetes mellitus (T2DM). METHODS: From
      1995 through 1996, 664 T2DM patients visited our hospital for the first time and
      were subsequently examined 4 times or more and at least once annually. At first
      visit, 326 had normoalbuminuria, 644 had an estimated glomerular filtration rate
      (eGFR) of >= 45 ml/min/1.73 m(2), 526 had no diabetic retinopathy and 609 had no
      severe non-proliferative diabetic retinopathy (NPDR). They were followed through
      June 2012, at the latest. RESULTS: Ninety patients developed microalbuminuria, 76
      showed decrease of eGFR to <45 ml/min/1.73 m(2), 113 developed mild-moderate NPDR
      and 50 progression to severe NPDR. The unadjusted, age- and sex-adjusted and
      multivariate-adjusted hazard ratios for development and progression of
      nephropathy, but not retinopathy, increased across tertiles of the standard
      deviation (SD) of SBP. Both the SD and coefficient of variation (CV) of SBP were
      significant predictors of development and progression of nephropathy, but not
      retinopathy, independently of mean SBP. CONCLUSION: Visit-to-visit SBP
      variability is an independent predictor of development and progression of
      diabetic nephropathy, but not retinopathy, in T2DM patients.

PMID- 24332764
TI  - Does bariatric surgery adversely impact on diabetic retinopathy in persons with
      morbid obesity and type 2 diabetes? A pilot study.
AB  - AIMS: To assess the incidence and progression of diabetic retinopathy (DR) 12
      months post bariatric surgery in persons with morbid obesity and type 2 diabetes.
      METHODS: A retrospective pilot analysis of electronic hospital records between
      1998 and 2012. RESULTS: 40 of 148 subjects had pre- and post-surgery DR
      screening. Of those without DR pre-surgery 1.5% (n = 26) progressed to minimum
      background DR (BDR) post surgery. Those with minimum BDR (n = 9) pre-surgery
      revealed no progression, with 55.6% (n = 5) showing evidence of regression. One
      person with moderately severe BDR and two with pre-proliferative DR (PPDR) prior
      to surgery experienced progression. Two persons with PPDR prior to surgery
      remained under the hospital eye services and were therefore not eligible to be re
      assessed by the screening service. CONCLUSIONS: There was a low incidence of new
      DR and progression of DR in those either without evidence of retinopathy or with
      minimal BDR prior to surgery with some subjects showing evidence of regression.
      There was however a risk of progression of DR in those with moderate BDR or
      worse, and should therefore be monitored closely post-surgery.

PMID- 24332765
TI  - Timing of peritoneal dialysis initiation and mortality: analysis of the Canadian
      Organ Replacement Registry.
AB  - BACKGROUND: Several observational studies of hemodialysis patients show an
      association between early dialysis therapy initiation and increased mortality.
      Few studies have examined this association among peritoneal dialysis patients.
      STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of
      8,047 incident peritoneal dialysis patients who started dialysis therapy in 2001
      2009 and were treated in Canada. PREDICTOR: Estimated glomerular filtration rate
      (eGFR) at dialysis therapy initiation. Defined early, mid, and late starts as
      eGFR>10.5, 7.5-10.5, and <7.5mL/min/1.73m(2), respectively. OUTCOMES: Time to
      death. MEASUREMENTS: Proportional piecewise exponential survival models to
      compare mortality (overall and early) for the 3 predictor groups. RESULTS:
      Between 2001 and 2009, the proportion of patients starting peritoneal dialysis
      therapy as early starts increased from 29% (95% CI, 26%-32%) to 44% (95% CI, 41%
      47%). Compared with the late-start group, the overall mortality rate was not
      higher for the early- (adjusted HR, 1.08; 95% CI, 0.96-1.23) or mid-start
      (adjusted HR, 0.96; 95% CI, 0.86-1.09) groups. However, when examined yearly,
      patients in the early-start group were significantly more likely to die within
      the first year of dialysis therapy compared with those in the late-start group
      (adjusted HR, 1.38; 95% CI, 1.10-1.73), but not in subsequent years. LIMITATIONS:
      Bias and residual confounding may have influenced the observed relationship
      between predictor and outcome. CONCLUSIONS: Patients are initiating peritoneal
      dialysis therapy at increasingly higher eGFRs. Contrary to most observational
      studies assessing hemodialysis, the early initiation of peritoneal dialysis
      therapy, at eGFR>10.5mL/min/1.73m(2), is not associated with increased mortality.

PMID- 24332766
TI  - Fluid management in adults and children: core curriculum 2014.

PMID- 24332767
TI  - Ten common mistakes in the management of lupus nephritis.
AB  - Management of patients with lupus nephritis can be complex and challenging. We
      suggest that there are some widely held misconceptions about lupus, and
      unfortunately, these underpin the treatment of many patients. There is little
      evidence to support the common assumption that intravenous pulse cyclophosphamide
      is the best treatment for lupus nephritis. Although there is much focus on which
      immunosuppressive agent to use, too little attention is paid to the proper dose
      and duration of corticosteroids and concomitant therapy with antimalarial agents.
      Many clinicians reflexively perform kidney biopsies when these biopsies may be
      high risk and not influence therapy. There is little emphasis on or awareness of
      nonadherence to therapy, which is an underappreciated cause of treatment
      resistance. Resolution of proteinuria and hematuria can take a long time, and
      immunotherapy should not be intensified based on urine sediment alone.
      Furthermore, the intensity of the immunosuppression must be considered in the
      context of lupus nephritis class and duration of kidney damage. Finally,
      clinicians are aware of the risks of pregnancy in the face of active lupus, but
      assume that their patients also are aware of this and forget to discuss this with
      them. With a combined experience of more than 50 years in managing children and
      adults with lupus, we offer our impression of recurrent mistakes in the
      management of lupus in general, with a focus on treatment of lupus nephritis. 

PMID- 24332768
TI  - Bartonella endocarditis-associated glomerulonephritis: a case report and review
      of the literature.
AB  - Infectious endocarditis is associated with a number of systemic manifestations,
      including kidney disease. Kidney manifestations, including hematuria, parenchymal
      infarction, and glomerulonephritis, may affect as many as 40%-50% of patients
      with infective endocarditis. In a minority of cases of infective endocarditis,
      routine bacterial cultures do not yield an offending organism. Bartonella species
      are a known and relatively common cause of culture-negative endocarditis and have
      been associated with the development of endocarditis-associated
      glomerulonephritis. We present a case of Bartonella endocarditis-associated
      glomerulonephritis in which recognition of a characteristic immunofluorescent
      pattern and thorough investigation of the clinical history led to this uncommon
      diagnosis. 

PMID- 24332769
TI  - A critical period in lifespan of male rats coincides with increased oxidative
      stress.
AB  - The oxidative stress theory of aging has provided the best possible explanation
      for the processes which accompany aging and has received much support, however,
      in the last few years there have been questions regarding the validity of this
      theory. We have conducted experiments to determine an array of oxidative stress
      parameters in blood of male rats at various intervals (1, 4, 8, 12, 18 and 24
      months) during their entire lifespan. Established protocols were used to measure
      plasma antioxidant capacity, erythrocyte plasma membrane redox system (PMRS),
      lipid and protein oxidation in erythrocytes and plasma, and erythrocyte
      glutathione (GSH). Our results on the total plasma antioxidant potential, PMRS in
      erythrocytes, protein and lipid peroxidation, and intracellular reduced GSH
      provide evidence that oxidative stress is minimal till approximately one-third of
      the total lifespan (8 months) and there is a spurt in oxidative stress between 8
      and 12 months. The identification of a period (corresponding to 8-12 months) in
      the lifespan of rats coinciding with an spurt in oxidative stress is an
      interesting finding. No such report is available in humans or in any other model
      systems during aging. 

PMID- 24332771
TI  - The heterogeneous health latent classes of elderly people and their socio
      demographic characteristics in Taiwan.
AB  - The health care needs of elderly people were influenced by their heterogeneity.
      This study aimed to identify the health latent classes of elderly people by using
      latent class analysis to deal with heterogeneity and examine their socio
      demographic characteristics. Data came from the 2005 National Health Interview
      Survey (NHIS) in Taiwan. In total, 2449 elderly individuals with available health
      indicators were examined in latent class analysis (LCA), and 2217 elderly
      community-dwellings with complete socio-demographic data were analyzed by
      multinomial logistic regression. Four health latent classes were identified which
      included 1066 (43.5%) people in the High Comorbidity (HC), 152 (6.2%) in the
      Functional Impairment (FI), 252 (10.3%) in the Frail (FR), and 979 (40.0%) in the
      Relatively Healthy (RH) group. Multinomial logistic regressions revealed socio
      demographic characteristics among health classes. The variables associated with
      an increased likelihood of being in the FR group were age, female, and living
      with families. They were also correlated to ethnicity and educations. Apart from
      age and gender, the Functional Impairment group was less likely to be ethnicity
      of Hakka, more likely to live with others than were the RH group. The HC group
      tended to be younger, with higher educations, and more likely to live in urban
      area than the Functional Impairment group. The correlations between health
      classes and socio-demographic factors were discussed. The health status of
      elderly people includes a variety of health indicators. A person-centered
      approach is critical to identify the health heterogeneity of elderly people and
      manage their care needs by targeting differential aging. 

PMID- 24332770
TI  - Do Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD)
      progress differently?
AB  - Our study aimed to compare cognitive status and declines in AD with/without small
      vessel disease (SVD) and SIVD at baseline and 1-year follow-up. Patients with
      Alzheimer's disease without small vessel disease (AD(-)SVD) (n=148), Alzheimer's
      disease with small vessel disease (AD(+)SVD) (n=94) and SIVD (n=60) were
      recruited from database of multiple centers in Korea. Basic demographics and
      detailed neuropsychological results were compared. AD, regardless of SVD, showed
      worse memory and better executive function than SIVD at baseline. Mini-Mental
      State Examination scores and visual memory function declined more in AD than
      those in SIVD whereas Barthel Activities of Daily Living (B-ADL) scores declined
      more in SIVD. AD showed different patterns of cognitive impairment compared with
      SIVD. After 1 year, AD showed more rapid cognitive decline in some domains.
      Further investigations with longer follow-up duration may be needed to confirm
      the cumulative effects of SVD in AD and different patterns of decline between AD
      and SIVD. 

PMID- 24332772
TI  - SUNCT (Short-lasting unilateral neuralgiform headache attack with conjunctival
      injection and tearing) associated with pituitary lesion.

PMID- 24332773
TI  - Learning skills and academic performance in children and adolescents with absence
      epilepsy.
AB  - INTRODUCTION: Although cognitive and learning disorders have been described in
      patients with epilepsy, very few studies focus on specific disorders such as
      absence epilepsy. The aim of this study was to evaluate learning skills and
      academic performance in children and adolescents with absence epilepsy. METHODS:
      Observational case-control study. Cases were chosen from the Central League
      against Epilepsy's clinic in Bogota, Colombia. Controls were selected from a
      private school and matched with cases by age, school year, and sex. Medical
      history, seizure frequency, antiepileptic treatment, and academic performance
      were assessed. Academic abilities were tested with Bateria de Aptitudes
      Diferenciales y Generales (BADyG) (a Spanish-language test of differential and
      general aptitudes). Data were analysed using Student t-test. RESULTS: The sample
      consisted of 19 cases and 19 controls aged between 7 and 16. In 15 patients,
      seizures were controlled; all patients had received antiepileptic medication at
      some point and 78.9% were actively being treated. Although cases had higher rates
      of academic failure, a greater incidence of grade retention, and more therapeutic
      interventions than controls, these differences were not significant. Similarly,
      there were no significant differences on the BADyG test, except for the immediate
      memory subcategory on which cases scored higher than controls (P=.0006).
      CONCLUSION: Children treated pharmacologically for absence epilepsy, whose
      seizures are controlled, have normal academic abilities and skills for their age.

PMID- 24332774
TI  - Broad bean (Vicia faba) consumption and Parkinson's disease: a natural source of
      L-dopa to consider.

PMID- 24332775
TI  - Effect of iron deficiency on the expression of insulin-like growth factor-II and
      its receptor in neuronal and glial cells.
AB  - INTRODUCTION: Many studies have demonstrated that iron deficiency modifies the
      normal function of the central nervous system and alters cognitive abilities.
      When cellular damage occurs in the central nervous system, neuroprotective
      mechanisms, such as the production of neurotrophic factors, are essential in
      order for nervous tissue to function correctly. Insulin-like growth factor II
      (IGF- II) is a neurotrophic factor that was recently shown to be involved in the
      normal functioning of cognitive processes in animal models. However, the impact
      of iron deficiency on the expression and function of this molecule has not yet
      been clarified. METHODS: Mixed primary cell cultures from the central nervous
      system were collected to simulate iron deficiency using deferoxamine. The
      expression of IGF-I, IGF-II, IGF-IR, and IGF-IIR was determined with the western
      blot test. RESULTS: We observed increased expression of IGF-II, along with a
      corresponding decrease in the expression of IGF-IIR, in iron-deficient mixed
      primary cell cultures. We did not observe alterations in the expression of these
      proteins in isolated microglia or neuronal cultures under the same conditions. We
      did not detect differences in the expression of IGF-I and IGF-IR in iron
      deficient cultures. CONCLUSIONS: In vitro iron deficiency increases the
      expression of IGF-II in mixed glial cell cultures, which may have a beneficial
      effect on brain tissue homeostasis in a situation in which iron availability is
      decreased.

PMID- 24332776
TI  - Progressive gait disorder and epilepsy secondary to venous stroke due to dural
      arteriovenous fistula type iii.

PMID- 24332777
TI  - Recurrent lacunar ischaemic stroke due to resistance to antiplatelet treatment:
      examining the need for personalised antithrombotic therapy.

PMID- 24332778
TI  - Magnetic resonance imaging findings after acute carbon monoxide poisoning.

PMID- 24332779
TI  - Delayed-onset encephalopathy caused by carbon monoxide poisoning: resolution in a
      patient treated with citicoline.

PMID- 24332780
TI  - Is the fogging effect related to futile recanalisation?

PMID- 24332781
TI  - Our experience with the aetiological diagnosis of global developmental delay and
      intellectual disability: 2006-2010.
AB  - INTRODUCTION: Global developmental delay (GDD) and intellectual disability (ID)
      are common reasons for consultation in paediatric neurology. Results from
      aetiological evaluations of children with GDD/ID vary greatly, and consequently,
      there is no universal consensus regarding which studies should be performed.
      MATERIAL AND METHOD: We review our experience with determining aetiological
      diagnoses for children with GDD/ID who were monitored by the paediatric neurology
      unit over the 5-year period between 2006 and 2010. RESULTS: During the study
      period, 995 children with GDD/ID were monitored. An aetiological diagnosis was
      established for 309 patients (31%), but not in 686 (69%), despite completing
      numerous tests. A genetic cause was identified in 142 cases (46% of the total
      aetiologies established), broken down as 118 cases of genetic encephalopathy and
      24 of metabolic hereditary diseases. Our data seem to indicate that diagnosis is
      easier when GDD/ID is associated with cerebral palsy, epilepsy, infantile
      spasms/West syndrome, or visual deficit, but more difficult in cases of autism
      spectrum disorders. Genetic studies provide an increasing number of aetiological
      diagnoses, and they are also becoming the first step in diagnostic studies. Array
      CGH (microarray-based comparative genomic hybridisation) is the genetic test with
      the highest diagnostic yield in children with unexplained GDD/ID. DISCUSSION: The
      cost-effectiveness of complementary studies seems to be low if there are no
      clinically suspected entities. However, even in the absence of treatment,
      aetiological diagnosis is always important in order to provide genetic
      counselling and possible prenatal diagnosis, resolve family (and doctors')
      queries, and halt further diagnostic studies.

PMID- 24332782
TI  - Chorea secondary to striatal encephalitis due to anti-CV2/CRMP5 antibodies. Case
      description and review of the literature.

PMID- 24332783
TI  - Induction of mandibular tremor using electrolytic lesion of the ventrolateral
      striatum or using subchronic haloperidol therapy in male rats: an
      electromyographic comparison.
AB  - INTRODUCTION: Tremulous jaw movement (TJMs) in rats can be induced
      pharmacologically by striatal dopaminergic manipulation or electrolytic lesion of
      ventrolateral striatum (VLS). This tremor has neurochemical, anatomical and
      electromyographic (EMG) characteristics similar to those of tremor in Parkinson
      patients. However, the EMG characteristics of tremors generated by electrolytic
      lesion to the VLS have not yet been studied. METHOD: This study used
      electromyography to describe tremulous jaw movement generated by bilateral
      electrolytic lesion in the VLS and compare it to tremors induced using subchronic
      IP treatment with haloperidol, a dopaminergic D2 receptor antagonist. The
      experimental groups contained rats with a lesion in the ventrolateral striatum
      and rats on subchronic haloperidol treatment; the control group received only the
      vehicle. The EMG signal from the temporal muscle was recorded at baseline and
      during TJMs in all groups. RESULTS: TMJ frequencies were heterogeneous among the
      groups. Rats with VLS lesion showed higher amplitude and frequency values than
      the haloperidol-treated rats. Amplitudes at baseline also differed among the
      groups. CONCLUSIONS: We conclude that TMJs associated with electrolytic lesion to
      the VLS show a higher frequency and amplitude than tremors induced by
      haloperidol. This may be related to the way striatum neurons are affected.

PMID- 24332784
TI  - Stress at work in migraine patients: differences in attack frequency.
AB  - INTRODUCTION: Migraine is a common and prevalent disease that contributes to
      health expenditure and interferes with quality of life. Our goal was to analyse
      the level of stress at work in a sample of migraine and its possible association
      with the chronicity of the process MATERIAL AND METHODS: We applied the Maslach
      Burnout Inventory, consisting of 22 items grouped into blocks that assess
      emotional exhaustion (EE), personal accomplishment (PA), depersonalisation at
      work (DP)] and positive influence (PI), to 94 consecutive subjects recruited in
      the outpatient clinic. Differences were compared between clinical groups (chronic
      migraine [CM]: > 15 days/month with headache over a 3-month period vs episodic
      migraine [EM]: < 15 days/month with headache) using the general linear model
      adjusted for age and MIDAS score RESULTS: The mean age was higher in the CM
      group. Mean MIDAS scores were 51 +/- 4.1 in CM, and 17.7 +/- 15 in EM (P=.001).
      Adjusted means for EE were 24.6 +/- 2.6 in CM patients, 16.2 +/- 2.6 in EM
      patients, and 13.4 +/- 2.3 (P=.03) in the healthy group. MIDAS scale scores were
      inversely correlated to PA (P<.05) DISCUSSION: Our results suggest that the level
      of EE at work is higher in EM than in CM patients, while PA levels decrease as
      impact on the MIDAS scale increases. The Maslach scale is a potentially useful
      tool for studying migraine impact. Surprisingly, EE is higher in patients with
      fewer episodes; this tendency could be related to stress adaptation mechanisms
      present in patients with chronic illness.

PMID- 24332785
TI  - Posterior territory stroke: endovascular treatment in patients with an occluded
      artery of Percheron.

PMID- 24332786
TI  - Acquired deforming hypertonia and contractures in elderly subjects: definition
      and prevalence in geriatric institutions (ADH survey).
AB  - OBJECTIVE: By proposing a new terminology (acquired deforming hypertonia or ADH)
      and a new definition for contractures, the main objective of this study was to
      establish their prevalence among institutionalized elderly patients. Secondary
      objectives were to analyze the negative impact of ADH and collect the opinions of
      clinicians on the possible treatments available. METHODOLOGY: A multicenter cross
      sectional study was conducted among residents of 39 geriatric institutions (29
      EHPAD and 10 USLD). All subjects presenting at least one ADH were surveyed over a
      one-week period. RESULTS: Among 3145 observed patients (mean age 88.9+/-9.7
      years) 22% (n=692) presented at least one ADH. In average, each patient presented
      4.4+/-3.2 ADHs. Negative consequences on self-care, nursing and difficulties in
      getting dressed were most frequently observed. Only 25.4% of clinicians
      considered the ADH to be potentially reversible. Physical therapy was the
      therapeutic option most frequently chosen over medication and surgery.
      CONCLUSION: This study confirms the important prevalence of ADH among elderly
      institutionalized patients. Consequences on the level of dependence were
      significant. It seems relevant to elaborate hierarchical therapeutic strategies
      in order to counter these disorders and the fatalism that ensues.

PMID- 24332787
TI  - Tuberculosis and TNFalpha antagonists--what are we missing?

PMID- 24332788
TI  - Episodic future thinking as a predictor of children's prospective memory.
AB  - The primary goal of this study was to investigate the relationship among
      retrospective memory, episodic future thinking, and event-based prospective
      memory performance in preschool, first-grade, and second-grade children. A total
      of 160 children took part in the experiment. The study included participants from
      four age groups: 4-year-olds, 5-year-olds, 6-year-olds, and 7-year-olds.
      Participants were administered a recognition memory task, a task to test the
      ability to pre-experience future events, and an event-based prospective memory
      task. Data were submitted to correlational analyses, analyses of variance
      (ANOVAs), and logistic regression analyses. Results showed that, overall, all of
      these abilities improve with age and are significantly correlated with one
      another. However, when partialling out age and retrospective memory, episodic
      future thinking and prospective memory performance remained correlated. Logistic
      regression further showed that age and episodic future thinking abilities were
      significant predictors of prospective memory performance independent of
      retrospective memory abilities. 

PMID- 24332789
TI  - Atmospheric input of 137Cs and 239,240Pu isotopes in Korea after the Fukushima
      nuclear power plant accident.
AB  - Caesium isotopes ((134)Cs and (137)Cs) and (239,240)Pu in rainwater and dry
      deposition have been analyzed by Korea Research Institute of Standards and
      Science (KRISS) since the Fukushima nuclear power plant (NPP) accident in March
      2011. The concentrations of (239,240)Pu and (137)Cs in the rainwater are 2.6+/
      1.0 to 15+/-3 uBq/kg and 0.01 to 0.36 mBq/kg, respectively. The concentrations
      are concordant to those observed before the Fukushima NPP accident, on the other
      hand, the monthly depositional flux of (239,240)Pu and (137)Cs are much lower
      than the amounts observed after Fukushima NPP accident and in Monaco in 1998
      2001. This confirms that the Fukushima NPP accident caused no significant impact
      in Korea.

PMID- 24332790
TI  - Sex differences in the effects of estradiol in the nucleus accumbens and striatum
      on the response to cocaine: neurochemistry and behavior.
AB  - BACKGROUND: Females exhibit more rapid escalation of cocaine use and enhanced
      cocaine-taking behavior as compared to males. While ovarian hormones likely play
      a role in this increased vulnerability, research has yet to examine the role of
      estradiol in affecting the behavioral and neurological response to cocaine in a
      brain region- and sex-specific way. METHODS: First, we examined stereotypy and
      locomotor sensitization after repeated cocaine administration (10 mg/kg i.p.) in
      intact (SHAM) and castrated (CAST) males, and ovariectomized (OVX) females
      treated with 5 MUg estradiol benzoate (EB) or vehicle (OIL). Next, we used in
      vivo microdialysis to examine the effects of acute EB treatment on cocaine
      induced DA in the regions mediating the display of these behaviors (i.e., the
      dorsolateral striatum, DLS; and the nucleus accumbens, NAc; respectively).
      RESULTS: We find that EB enhances sensitization of cocaine-induced stereotypy in
      OVX females after 12 days of cocaine treatment, and after a 10-day withdrawal.
      Similarly, the OVX/EB females show enhanced locomotor sensitization compared to
      the other three groups on the same days. Using in vivo microdialysis to assess
      the neurochemical response, we find that EB rapidly enhances cocaine-induced DA
      in DLS dialysate of OVX females but not CAST males, and has no effect in NAc of
      either sex. CONCLUSIONS: With these experiments, we show that there are sex
      differences in the effects of estradiol to preferentially enhance the response to
      cocaine in the DLS over the NAc in females, which may contribute to the
      preferential sensitization of stereotypy in females.

PMID- 24332791
TI  - Mercury cycling in agricultural and managed wetlands, Yolo Bypass, California:
      spatial and seasonal variations in water quality.
AB  - The seasonal and spatial variability of water quality, including mercury species,
      was evaluated in agricultural and managed, non-agricultural wetlands in the Yolo
      Bypass Wildlife Area, an area managed for multiple beneficial uses including bird
      habitat and rice farming. The study was conducted during an 11-month period (June
      2007 to April 2008) that included a summer growing season and flooded conditions
      during winter. Methylmercury (MeHg) concentrations in surface water varied over a
      wide range (0.1 to 37ngL(-1) unfiltered; 0.04 to 7.3ngL(-1) filtered). Maximum
      MeHg values are among the highest ever recorded in wetlands. Highest MeHg
      concentrations in unfiltered surface water were observed in drainage from wild
      rice fields during harvest (September 2007), and in white rice fields with
      decomposing rice straw during regional flooding (February 2008). The ratio of
      MeHg to total mercury (MeHg/THg) increased about 20-fold in both unfiltered and
      filtered water during the growing season (June to August 2007) in the white and
      wild rice fields, and about 5-fold in fallow fields (July to August 2007), while
      there was little to no change in MeHg/THg in the permanent wetland. Sulfate
      bearing fertilizer had no effect on Hg(II) methylation, as sulfate-reducing
      bacteria were not sulfate-limited in these agricultural wetlands. Concentrations
      of MeHg in filtered and unfiltered water correlated with filtered Fe, filtered
      Mn, DOC, and two indicators of sulfate reduction: the SO4(2-)/Cl(-) ratio, and
      delta(34)S in aqueous sulfate. These relationships suggest that microbial
      reduction of SO4(2-), Fe(III), and possibly Mn(IV) may contribute to net Hg(II)
      methylation in this setting. 

PMID- 24332792
TI  - A critical view on the eco-friendliness of small hydroelectric installations.
AB  - Renewable energy sources are widely perceived as 'clean', 'green', and
      'inexhaustible'. In recent years the spectre of global warming and ocean
      acidification, which has been primarily attributed to fossil fuel burning, has
      brought renewable energy at the forefront of most climate change mitigation
      strategies. There is strong advocacy for large-scale substitution of conventional
      energy sources with the renewables on the premise that such a move would
      substantially reduce environmental degradation and global warming. These
      sentiments are being echoed by scientists and policy makers as well as
      environmental activists all over the world. 'Small hydro', which generally
      represents hydroelectric power projects of capacities 25 MW or lower, is one of
      the renewable energy options which is believed to be clean and sustainable even
      as its bigger version, large hydro, is known to cause several strongly adverse
      environmental impacts. This paper brings out that the prevailing perception of
      'eco-friendliness' of small hydro is mainly due to the fact that it has only been
      used to a very small extent so far. But once it is deployed at a scale comparable
      to fossil fuel use, the resulting impacts would be quite substantially adverse.
      The purpose is not to denegrade small hydro, less so to advocate use of fossil
      fuels. It, rather, is to bring home the point that a much more realistic and
      elaborate assessment of the likely direct as well as indirect impacts of
      extensive utilization of this energy source than has been done hitherto is
      necessary.

PMID- 24332793
TI  - Handle energy resources with care.
AB  - While politicians discuss rules to improve the efficacy of global energy
      consumption and to limit environmental pollution, the mammalian body has numerous
      mechanisms to efficiently use nutrient resources and appropriately extract
      energy. A new mechanism has recently been identified by the group of Fredrik
      Backhed in Cell Host & Microbe. 

PMID- 24332794
TI  - Self-attribution bias during continuous action-effect monitoring in patients with
      schizophrenia.
AB  - The feeling of being the source and controller of one's actions and their effects
      in the outside world is an important aspect of our sense of self. Disturbances in
      this sense of agency (SoA) were observed in schizophrenia and have been linked to
      impairments in sensorimotor integration. We used a virtual-world action
      monitoring paradigm to investigate the SoA in 20 schizophrenic patients and 18
      healthy subjects. Participants continuously moved a virtual pen displayed on a
      computer screen using a touchpad device. The control they exceeded over the
      virtual pen was switched periodically between the participant and the computer.
      Participants were requested to monitor their actions and the effects on the
      virtual pen, and indicate loss or regain of control over the pen's movement by
      button presses. The numbers of erroneous external attribution of action effects
      (false negative agency judgements) and erroneous self-attribution (false positive
      agency judgements) were not significantly different in patients and healthy
      subjects. However, patients showed a significant increase in the duration of
      false negative agency judgements. Moreover, the number of false negative agency
      judgements as well as the number and the duration of false positive agency
      judgements were negatively correlated with the performance in cognitive tests
      (BACS) in the patient group only. Our findings indicate that the evaluation
      system to detect a mismatch between actions and their effects in the outside
      world is probably more rigid in schizophrenic patients, which leads to an
      increased self-attribution bias for action effects, as commonly found in
      delusions of control. The impairment in sensorimotor integration may be
      compensated for by stronger cognitive control. 

PMID- 24332795
TI  - Preservation and compensation: the functional neuroanatomy of insight and working
      memory in schizophrenia.
AB  - BACKGROUND: Poor insight in schizophrenia has been theorised to reflect a
      cognitive deficit that is secondary to brain abnormalities, localized in the
      brain regions that are implicated in higher order cognitive functions, including
      working memory (WM). This study investigated WM-related neural substrates of
      preserved and poor insight in schizophrenia. METHOD: Forty stable schizophrenia
      outpatients, 20 with preserved and 20 with poor insight (usable data obtained
      from 18 preserved and 14 poor insight patients), and 20 healthy participants
      underwent functional magnetic resonance imaging (fMRI) during a parametric 'n
      back' task. The three groups were preselected to match on age, education and
      predicted IQ, and the two patient groups to have distinct insight levels.
      Performance and fMRI data were analysed to determine how groups of patients with
      preserved and poor insight differed from each other, and from healthy
      participants. RESULTS: Poor insight patients showed lower performance accuracy,
      relative to healthy participants (p=0.01) and preserved insight patients
      (p=0.08); the two patient groups were comparable on symptoms and medication.
      Preserved insight patients, relative to poor insight patients, showed greater
      activity most consistently in the precuneus and cerebellum (both bilateral)
      during WM; they also showed greater activity than healthy participants in the
      inferior-superior frontal gyrus and cerebellum (bilateral). Group differences in
      brain activity did not co-vary significantly with performance accuracy.
      CONCLUSIONS: The precuneus and cerebellum function contribute to preserved
      insight in schizophrenia. Preserved insight as well as normal-range WM capacity
      in schizophrenia sub-groups may be achieved via compensatory neural activity in
      the frontal cortex and cerebellum.

PMID- 24332796
TI  - Patients with schizophrenia are impaired when learning in the context of pursuing
      rewards.

PMID- 24332797
TI  - Clinical and biological characteristics of diabetic patients under age 40 in
      Cameroon: relation to autoantibody status and comparison with Belgian patients.
AB  - AIMS: We investigated the prevalence of diabetes autoantibodies (Abs) in
      Cameroonian patients and controls, assessed their contribution in disease
      classification and compared results with data from Belgium. METHODS: Abs against
      GAD (GADA), IA-2 (IA-2A) and zinc transporter 8 (ZnT8A) were assessed in 302
      recently diagnosed Cameroonian patients with diabetes and 184 control subjects
      without diabetes aged below 40 years. RESULTS: Only 27 (9%) Cameroonian patients
      were younger than 15 years. Overall, 29% of patients presented at least one
      diabetes-associated antibody vs 9% in healthy controls (24% vs 7% for GADA
      (p<0.001), 10% vs 3% for IA-2A (p<0.006), 4% vs 2% for ZnT8A). Ab(+) patients had
      lower C-peptide levels (p<0.001), were more often insulin-treated (p<0.002) and
      were as frequently diagnosed with type 1 diabetes as Ab(-) patients. Only 43% of
      Ab(+) patients aged 15-39 years were clinically classified as having type 1
      diabetes in Cameroon vs 96% in Belgium (p<0.001). Not one Ab(+) Cameroonian
      patient carried HLA-DQ2/DQ8 genotype vs 23% of Belgian Ab(+) patients (p<0.001).
      Younger age at diagnosis and antibody positivity were independent predictors of
      insulin therapy. Ab(+) Cameroonian patients were older (p<0.001), had higher BMI
      (p<0.001) and lower Ab titers than Belgian Ab(+) patients. In ketonuric patients,
      prevalence of autoantibodies was similar as in non-ketonuric patients.
      CONCLUSIONS: In Cameroonian patients with diabetes aged under 40 years, antibody
      positivity is not clearly related to disease phenotype, but may help predict the
      need for insulin treatment.

PMID- 24332799
TI  - An alternative method for predicting the risk of postoperative complications in
      lung resection.
AB  - OBJECTIVES: The aims of this study were to design a best fit linear regression
      model to estimate VO2max (estimated VO2) and to compare the ability of VO2 values
      (measured and estimated) predicting cardiorespiratory complications in a series
      of patients undergoing lung resection for lung cancer. METHOD: This was a
      prospective, observational study performed in 83 patients. Variables analyzed
      were: demographic characteristics, comorbidity, body mass index (BMI), FEV1%,
      FVC%, diffusion capacity (DLCO%), mean daily distance walked in kilometers,
      VO2max measured by cardio-pulmonary exercise test (CPET) and postoperative
      complications. Descriptive and comparative statistical analysis of the variables
      was performed using the Mann-Whitney test for categorical variables and the
      Student's t-test for continuous variables. A new linear regression model was
      designed, where the dependent variable (measured VO2max) was estimated by the
      distance, DLCO% and age, resulting in the estimated VO2. The predictive power of
      the measured and estimated consumption was analyzed using the Student's t-test,
      grouping by the occurrence or absence of cardiorespiratory complications.
      RESULTS: Both groups were homogeneous for age, sex, BMI, FEV1%, DLCO%,
      comorbidity, type of resection performed and mean distance walked per day.
      Estimated VO2 and measured VO2 were normally distributed (K-Smirnov test, P>.32).
      VO2 means estimated by the model (age, DLCO% and mean distance walked per day)
      were significantly different between patients with and without complications
      (Student's t test, P=.037) compared with measured VO2 values, which did not
      differentiate groups (Student's t test, P=.42). CONCLUSION: The VO2max estimated
      by the model is more predictive in this case series than the VO2max measured
      during a standard exercise test.

PMID- 24332798
TI  - Maternal-fetal metabolic gene-gene interactions and risk of neural tube defects.
AB  - Single-gene analyses indicate that maternal genes associated with metabolic
      conditions (e.g., obesity) may influence the risk of neural tube defects (NTDs).
      However, to our knowledge, there have been no assessments of maternal-fetal
      metabolic gene-gene interactions and NTDs. We investigated 23 single nucleotide
      polymorphisms among 7 maternal metabolic genes (ADRB3, ENPP1, FTO, LEP, PPARG,
      PPARGC1A, and TCF7L2) and 2 fetal metabolic genes (SLC2A2 and UCP2). Samples were
      obtained from 737 NTD case-parent triads included in the National Birth Defects
      Prevention Study for birth years 1999-2007. We used a 2-step approach to evaluate
      maternal-fetal gene-gene interactions. First, a case-only approach was applied to
      screen all potential maternal and fetal interactions (n = 76), as this design
      provides greater power in the assessment of gene-gene interactions compared to
      other approaches. Specifically, ordinal logistic regression was used to calculate
      the odds ratio (OR) and 95% confidence interval (CI) for each maternal-fetal gene
      gene interaction, assuming a log-additive model of inheritance. Due to the number
      of comparisons, we calculated a corrected p-value (q-value) using the false
      discovery rate. Second, we confirmed all statistically significant interactions
      (q < 0.05) using a log-linear approach among case-parent triads. In step 1, there
      were 5 maternal-fetal gene-gene interactions with q < 0.05. The "top hit" was an
      interaction between maternal ENPP1 rs1044498 and fetal SLC2A2 rs6785233
      (interaction OR = 3.65, 95% CI: 2.32-5.74, p = 2.09*10(-8), q=0.001), which was
      confirmed in step 2 (p = 0.00004). Our findings suggest that maternal metabolic
      genes associated with hyperglycemia and insulin resistance and fetal metabolic
      genes involved in glucose homeostasis may interact to increase the risk of NTDs.

PMID- 24332800
TI  - Biceps tenodesis is a viable option for salvage of failed SLAP repair.
AB  - BACKGROUND: Outcomes of arthroscopic superior labral anterior-posterior (SLAP)
      repairs have been well reported with generally favorable outcomes. Unfortunately,
      a percentage of patients remain dissatisfied or suffer further injury after SLAP
      repair and may seek additional treatment. The purpose of this study was to
      evaluate the surgical outcomes of biceps tenodesis for failed SLAP repairs.
      METHODS: A retrospective review of all patients undergoing biceps tenodesis was
      completed. Inclusion criteria were previous SLAP repair and subsequent revision
      biceps tenodesis. Exclusion criteria were additional shoulder procedures
      including rotator cuff repair, instability procedures, and preoperative frozen
      shoulder. Objective outcomes were postoperative assessments with Constant score,
      American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation,
      Simple Shoulder Test, and Veterans RAND 36-Item Health Survey. Physical
      examination was conducted to determine postoperative range of motion and strength
      compared with the nonoperative shoulder. RESULTS: A cohort of 24 patients was
      identified, and of these, 17 patients (71%) completed the study at 2 years'
      follow-up. The average postoperative Constant score was 84.4; American Shoulder
      and Elbow Surgeons score, 75.5; Single Assessment Numeric Evaluation score,
      73.1%; Simple Shoulder Test score, 9.2; and Veterans RAND 36-Item Health Survey
      score, 76.1. Postoperative range of motion of the operative shoulder returned to
      near that of the asymptomatic nonoperative shoulder. Workers' compensation status
      led to inferior results. CONCLUSIONS: Options for patients with a failed prior
      SLAP repair are limited. As a salvage operation for failed SLAP repair, biceps
      tenodesis serves the majority of patients well, with favorable outcomes by
      validated measures and excellent shoulder range of motion and elbow strength at 2
      years' follow-up. Workers' compensation status may predispose patients to poorer
      outcomes.

PMID- 24332801
TI  - Religious factors associated with alcohol involvement: results from the Mauritian
      Joint Child Health Project.
AB  - BACKGROUND: The purpose of this study was to examine religious factors associated
      with alcohol involvement in Mauritius. The three main religions on the island,
      Hinduism, Catholicism, and Islam, promote different views of the appropriate use
      of alcohol. Based on reference group theory, we hypothesized that both the
      content of a religion's alcohol norms and an individual's religious commitment
      would relate to alcohol use behavior. METHODS: Participants were from the Joint
      Child Health Project, a longitudinal study that has followed a birth cohort of
      1.795 individuals since 1972 when they were 3 years old. All available
      participants (67%; 55% male) were assessed in mid-adulthood on religious
      variables, lifetime drinking, and lifetime alcohol use disorders. RESULTS: Across
      religions, individuals who viewed their religion as promoting abstinence were
      less likely to be drinkers. Religious commitment was associated with reduced
      probability of drinking only in those who viewed their religion as promoting
      abstinence. Among drinkers, abstention norms and religious commitment were not
      associated with lower likelihood of alcohol use disorders. In Catholics who
      viewed their religion as promoting abstinence and still were drinkers, high
      religious commitment was associated with increased risk for alcohol use
      disorders. CONCLUSIONS: Predictions based on reference group theory were largely
      supported, with religious norms and commitment differentially related to alcohol
      use and problems both across religions and among individuals within religions.
      Findings highlight the importance of examining multiple aspects of religion to
      better understand the relationship of religion with alcohol behaviors.

PMID- 24332802
TI  - Childhood and current ADHD symptom dimensions are associated with more severe
      cannabis outcomes in college students.
AB  - BACKGROUND: Numerous studies have shown that attention deficit/hyperactivity
      disorder (ADHD) is associated higher risk of cannabis use disorders (CUD).
      However, these studies are limited in that most did not: (a) differentiate the
      role of hyperactivity-impulsivity (HI) and inattention (IN); (b) control for
      associated psychopathology; and (c) consider more fine-grained CUD-related
      measures. Our aim was to clarify the unique and interactive contributions of
      inattention and hyperactivity symptoms to age of cannabis initiation and DSM-IV
      cannabis dependence, craving, and severity of problems related to cannabis use
      while statistically controlling for symptoms of comorbid psychopathology in a non
      clinical sample of young adults. METHODS: Cannabis variables, current use of
      cigarettes and alcohol, current and childhood ADHD, and comorbid internalizing
      and externalizing psychopathology were assessed in 376 male and female
      undergraduates. RESULTS: Results indicate that current and childhood IN were
      independently associated with more severe cannabis use, craving, and problem use
      related outcomes in young adulthood (p's<.01) and that childhood HI symptoms were
      associated with earlier initiation of cannabis (p<.01). Further, current IN
      symptoms moderated the relationships between level of use and more severe
      outcomes (p's<.01), such that higher IN strengthened positive associations among
      use and problem cannabis use. Associations with ADHD symptom dimensions and
      current use of alcohol and cigarettes were also present. CONCLUSIONS: Thus,
      current and childhood inattention symptoms as well as childhood hyperactive
      impulsive symptoms emerged as significant factors in cannabis-related outcomes in
      young adults, even after statistically controlling for important confounding
      variables.

PMID- 24332803
TI  - Do musculoskeletal physiotherapists believe the NICE guidelines for the
      management of non-specific LBP are practical and relevant to their practice? A
      cross sectional survey.
AB  - BACKGROUND: Evidence-based practice has become fundamentally important in the
      field of musculoskeletal physiotherapy, which include clinical practice
      guidelines, such as those developed by National Institute for Health and Clinical
      Excellence (NICE) for low back pain. OBJECTIVES: To gauge whether musculoskeletal
      physiotherapist working in the UK are compliant with the NICE guidelines for back
      pain, and if they believe them to be practical and relevant to their current
      practice. DESIGN: Descriptive cross-sectional voluntary electronic survey.
      METHODS: A survey of musculoskeletal physiotherapists currently working in the UK
      was conducted through an anonymous online data collection website over a two
      month data collection period. Data was collected about demographic details of
      participants, and their views about the NICE guidelines through a specially
      designed questionnaire, and are presented descriptively. RESULTS: Two hundred and
      twenty-three therapists participated. Following a thematic content analysis seven
      key themes were identified about the guidelines: they facilitated evidence-based
      practice; they were unrealistic and idealistic; they did not facilitate a
      multimodal approach; they promoted largely a passive approach; they challenged
      therapist autonomy; they were outdated; they lacked relevance and specificity.
      CONCLUSION: Musculoskeletal physiotherapists strongly believe in the principles
      of EBP, and thought the NICE back pain guidelines were relevant to their
      practice. However the recommendations made within the guidelines were not
      realistic in day to day practice and they impacted negatively on the practice in
      a number of ways.

PMID- 24332804
TI  - Standardization of alpha-L-iduronidase enzyme assay with Michaelis-Menten
      kinetics.
AB  - The lack of methodological uniformity in enzyme assays has been a long-standing
      difficulty, a problem for bench researchers, for the interpretation of clinical
      diagnostic tests, and an issue for investigational drug review. Illustrative of
      the problem, alpha-L-iduronidase enzyme catalytic activity is frequently measured
      with the substrate 4-methylumbelliferyl-alpha-L-iduronide (4MU-iduronide);
      however, final substrate concentrations used in different assays vary greatly,
      ranging from 25 MUM to 1425 MUM (Km ~ 180 MUM) making it difficult to compare
      results between laboratories. In this study, alpha-L-iduronidase was assayed with
      15 different substrate concentrations. The resulting activity levels from the
      same specimens varied greatly with different substrate concentrations but, as a
      group, obeyed the expectations of Michaelis-Menten kinetics. Therefore, for the
      sake of improved comparability, it is proposed that alpha-L-iduronidase enzyme
      assays should be conducted either (1) under substrate saturating conditions; or
      (2) when concentrations are significantly below substrate saturation, with
      results standardized by arithmetic adjustment that considers Michaelis-Menten
      kinetics. The approach can be generalized to many other enzyme assays.

PMID- 24332806
TI  - Small RNA-guided adaptive immunity: comment on "Diversity, evolution, and
      therapeutic applications of small RNAs in prokaryotic and eukaryotic immune
      systems" by Cooper and Overstreet.

PMID- 24332805
TI  - Quantitative neuroimaging in mucolipidosis type IV.
AB  - Mucolipidosis type IV (MLIV) is an autosomal recessive disorder resulting from
      mutations in the MCOLN1 gene. This gene encodes the endosomal/lysosomal transient
      receptor potential channel protein mucolipin-1 (TRPML1). Affected patients suffer
      from neurodevelopmental abnormalities and progressive retinal dystrophy. In a
      prospective natural history study we hypothesized the presence of an additional
      slow cerebral neurodegenerative process. We have recruited 5 patients, tested
      their neurodevelopmental status, and measured cerebral regional volumes and white
      matter integrity using MRI yearly. Over a period of up to 3 years, MLIV patients
      remained neurologically stable. There was a trend for increased cortical and
      subcortical gray matter volumes and increased ventricular size, while white
      matter and cerebellar volumes decreased. Mean diffusivity (MD) was increased and
      fractional anisotropy (FA) values were below normal in all analyzed brain
      regions. There was a positive correlation between motor scores of the Vineland
      Scale and the FA values in the corticospinal tract (corr coef 0.39), and a
      negative correlation with the MD values (corr coef -0.50) in the same brain
      region. We conclude from these initial findings that deficiency in mucolipin-1
      affects the entire brain but that there might be a selective regional cerebral
      neurodegenerative process in MLIV. In addition, these data suggest that diffusion
      weighted imaging might be a good biomarker for following patients with MLIV.
      Therefore, our findings may be helpful for designing future clinical trials.

PMID- 24332807
TI  - The comparison of effects of biologic agents on rheumatoid arthritis damage
      progression is biased by period of enrollment: data from a systematic review and
      meta-analysis.
AB  - OBJECTIVES: To indirectly compare the 12-month effects of available biologic
      agents in slowing RA radiographic progression. METHODS: A systematic review of
      literature of randomised, double-blind, controlled trials (RCTs) evaluating RA
      radiographic progression as end point was conducted using a PubMed searching of
      MEDLINE from January 1995 to May 2012. For each trial, the mean change from
      baseline of the standardised annual radiographic progression score (weighted for
      estimated annual progression rate) was estimated, and the effect size was
      calculated as the difference between biologic and non-biologic-treated groups. In
      order to optimise data homogeneity and improve RCTs comparison, a mixed-effect
      model was applied including previous responsiveness to methotrexate (MTX
      experienced or MTX-naive populations) and period of study enrollment as
      moderators. RESULTS: The PubMed search resulted in 183 references, and 14 were
      eligible for the meta-analysis. The analysis of study distribution in forest
      plots showed a high correlation between the study period of enrollment and the
      impact of biological therapy in both MTX-naive and MTX-experienced subgroups. In
      particular, effect size was the highest for older trials and progressively
      decreased in the most recent ones, suggesting a highest propensity to
      radiographic progression in populations enrolled in older trials. Some
      statistically significant differences among RCTs were found in both subgroups but
      were significantly biased by the different propensity to radiographic progression
      due to period of enrollment. CONCLUSIONS: Our meta-analysis demonstrated that
      period of enrollment deeply influence study population propensity to radiographic
      progression in each trial. This finding does not allow the indirect comparison of
      various biologic agents, despite our mixed-model significantly reducing
      heterogeneity among RCTs.

PMID- 24332809
TI  - Chondrocyte proliferation regulated by secreted luminal domain of ER stress
      transducer BBF2H7/CREB3L2.
AB  - The endoplasmic reticulum (ER) stress transducer BBF2H7/CREB3L2 is an ER-resident
      transmembrane transcription factor. In response to physiological ER stress, it is
      processed at the transmembrane region to generate a cytoplasmic N terminus, which
      contains a basic leucine zipper (bZIP) domain, and luminal C terminus. The BBF2H7
      N terminus functions as a transcription factor to promote the expression of ER
      Golgi trafficking-related genes and plays crucial roles in chondrocyte
      differentiation. Here, we found that the BBF2H7 C terminus is secreted into the
      extracellular space as a signaling molecule for cell-to-cell communication. The
      secreted BBF2H7 C terminus directly binds to both Indian hedgehog and its
      receptor Patched-1, followed by activation of Hedgehog signaling, resulting in
      promoting the proliferation of neighboring chondrocytes. The dual N- and C
      terminal functions of BBF2H7 triggered by physiological ER stress may allow
      chondrocytes to simultaneously regulate distinct cellular events for
      differentiation and proliferation in developing cartilage.

PMID- 24332810
TI  - Differences of salivary cortisol levels between long-term and short-term wearers
      of dento-maxillary prosthesis due to head and neck cancer resection.
AB  - PURPOSE: The purpose of this study was to use cortisol awakening response (CAR)
      to investigate the differences in daily life stress experienced by individuals
      wearing either a long-term (LT) or a short-term (ST) dento-maxillary prosthesis
      following head and neck cancer (HNC) resection. Also we used the University of
      Washington Quality of Life (UW-QOL) version 4 questionnaire to evaluate the
      differences in quality of life (QOL) scores between ST and LT wearers of a dento
      maxillary prosthesis. METHODS: Salivary samples were collected from 11 LT and 10
      ST prosthesis wearers on two consecutive days at two time points, immediately
      after waking up (T0) and 30min later (T30), by passive drool collection. Cortisol
      levels were measured using a high sensitivity salivary cortisol enzyme
      immunoassay kit (Salimetrics, LLC, State College, PA, USA) and CAR (the
      differences between the cortisol levels at T0 and T30) was compared between LT
      and ST prosthesis wearers. In addition, both the groups completed the UW-QOL
      questionnaire and the scores were compared. RESULTS: A significant difference was
      observed in CAR between the two groups. CAR of the ST prosthesis wearers was
      significantly lower compared with that of the LT prosthesis wearers; moreover,
      the ST prosthesis wearers revealed significantly lower total UW-QOL scores and
      there were significant differences in appearance, activity, recreation, speech,
      and anxiety. CONCLUSION: Within the limitations of this study, the findings
      suggest that individuals wearing ST dento-maxillary prostheses following HNC
      resection experience some sort of daily life stress and complicated socio
      demographic factors may influence their QOL.

PMID- 24332808
TI  - PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR
      activation via a ubiquitin-mediated circuitry.
AB  - PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage
      response (DDR). Although the role for PRP19 in splicing is well characterized,
      its role in the DDR remains elusive. Through a proteomic screen for proteins that
      interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as
      a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage
      sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19
      facilitates the accumulation of ATRIP, the regulatory partner of the ataxia
      telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites.
      Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of
      stalled replication forks, and progression of replication forks on damaged DNA.
      Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase
      failed to support the ATR response, revealing that PRP19 drives ATR activation by
      acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. 

PMID- 24332811
TI  - APOE gene polymorphisms and susceptibility to Creutzfeldt-Jakob disease.
AB  - Associations between apolipoprotein E (APOE) gene polymorphisms and Creutzfeldt
      Jakob disease (CJD) have been reported, but the results from many of these
      studies are conflicting. To investigate the association between APOE
      polymorphisms and CJD risk, we performed a meta-analysis. We used odds ratios
      (OR) with 95% confidence intervals (CI) to assess the strength of the
      association. The frequency of putative risk alleles in control subjects was
      estimated with the Mantel-Haenszel method. Cochran's Q statistic and the
      inconsistency index (I(2)) were used to test heterogeneity. Egger's test and an
      inverted funnel plot were used to assess bias. Our study included 11 published
      case-control studies with APOE genotyping, involving a total of 1001 CJD patients
      and 1211 controls. Overall, the APOE 34 (OR 1.37, 95% CI: 1.09-1.72), and APOE 44
      (OR 3.16, 95% CI: 1.37-7.26) genotypes and the APOE 4 (OR 1.41, 95% CI: 1.08
      1.85) allele were associated with an increased risk of CJD, and the APOE 33 (OR
      0.81, 95% CI: 0.67-0.97) genotype tended to protect against CJD. However, we did
      not find significant evidence supporting associations of the APOE 22 (OR 1.15,
      95% CI: 0.45-2.93), APOE 23 (OR 0.84, 95% CI: 0.64-1.09), or APOE 24 (OR 1.40,
      95% CI: 0.70-2.77) genotypes, nor the APOE 2 (OR 1.02, 95% CI: 0.73-1.42) or APOE
      3 (OR 0.82, 95% CI: 0.65-1.02) alleles with CJD using a fixed-effects model. Our
      results support a genetic association between APOE polymorphisms and CJD. 

PMID- 24332812
TI  - Intraprocedural retrieval of migrated coils during endovascular aneurysm
      treatment with the Trevo Stentriever device.
AB  - Coil migration during endovascular treatment of intracranial aneurysms occurs in
      2-6% of cases. As endovascular coiling of aneurysms has become increasingly
      popular and as endovascular technology continues to rapidly evolve, the
      prevalence of intraprocedural coil migration will invariably rise. Since coil
      masses are highly thrombogenic, migration out of the aneurysm sac into the parent
      artery may result in large territory infarcts which subsequently manifest as
      significant neurological morbidity. Therefore safe and timely retrieval of
      migrated coils is essential to avoiding poor angiographic and clinical outcomes.
      A 66-year-old woman with an unruptured 5 * 3mm, wide-necked posterior
      communicating artery aneurysm was referred for endovascular treatment. During
      coiling with the dual catheter technique, both initially deployed coils dislodged
      from the aneurysm sac and migrated distally into the middle cerebral artery.
      After failed retrieval with an Alligator device (Chestnut Medical Technologies,
      Menlo Park, CA, USA), we used two Trevo devices (Concentric Medical, Mountain
      View, CA, USA) in succession to successfully retrieve the migrated coils. The
      aneurysm was then occluded with stent-assisted coil embolization. There were no
      post-procedural angiographic or clinical complications. The patient was
      subsequently discharged home without neurological deficit. This case illustrates
      the first use of the Trevo device for retrieval of migrated coils during
      endovascular treatment of an intracranial aneurysm to our knowledge. Due to the
      lack of guidelines defining the standard management of intraprocedural coil
      migration, current strategies are based on retrospective review of published
      reports and expert opinion. We present a unique and effective method for
      endovascular retrieval of displaced coils using a Trevo Stentriever device.

PMID- 24332813
TI  - Reply to Letter to the editor by Davies et al.

PMID- 24332814
TI  - Esophagectomy combined with aortic segment replacement for esophageal cancer
      invading the aorta.
AB  - BACKGROUND: Surgical treatment for patients with esophageal carcinoma that
      invades the aorta locally (stage IIIc) remains a considerable challenge. This
      study aimed to introduce radical esophagectomy combined with off-pump descending
      aorta replacement in these patients and to assess the effects on both short-term
      and long-term outcomes. METHODS: The clinical data of 47 patients who had
      esophageal carcinoma invading the descending aorta and who underwent radical
      esophagectomy combined with off-pump aortic replacement between January 2001 and
      March 2012 in Jinling Hospital were retrospectively reviewed. The intraoperative,
      early postoperative, and follow-up results were analyzed. RESULTS: Overall, 80.9%
      and 19.1% of the patients had histopathologically confirmed aortic tunica
      adventitia invasion and media invasion, respectively. All patients received
      complete resection (R0) with an average intraoperative blood loss of 227.6+/-63.3
      mL. The mean operative time and aortic cross-clamping time were 4.9+/-1.3 hours
      and 17.0+/-3.2 minutes, respectively. Complications were observed in 59.6% of
      patients, with no hospital mortality, and all patients resumed an oral diet 1
      month after the procedure. The overall 1-, 3-, and 5-year survival rates were
      80.9%, 44.7%, and 21.3%, respectively, with a median survival time of 33.6
      months. CONCLUSIONS: In patients with esophageal carcinoma invading the aorta, it
      is feasible and safe to perform radical esophagectomy combined with off-pump
      descending aorta replacement to improve nutritional status and achieve
      satisfactory survival.

PMID- 24332815
TI  - The effect of guided flapless implant procedure on heat generation from implant
      drilling.
AB  - The objective of this study was to evaluate the heat generation in vitro during
      the flapless drilling procedure using surgical drill guides. Ten resin models
      with bilateral edentulous tooth spaces in the first and second molars in the
      mandible were used in this study. On one side of the mandible, drilling was
      performed with a flapless approach using a surgical drill guide. On the other
      side of the mandible, drilling was performed with a flap approach. The
      temperature changes were measured during final drilling by thermocouples. The
      mean maximum temperatures during drilling with guided flapless procedures were
      29.5  degrees C and 32.6  degrees C at the depths of 3 and 6 mm, respectively,
      whereas for flap procedures they were 29.4  degrees C and 31.3  degrees C. There
      was no statistically significant difference between the groups. These findings
      suggest that drilling with external irrigation in an up-and-down pumping motion
      may not lead to a significant increase the bone temperature during a flapless
      procedure using surgical drill guides. 

PMID- 24332816
TI  - Hydrogen peroxide generated by DUOX1 regulates the expression levels of specific
      differentiation markers in normal human keratinocytes.
AB  - BACKGROUND: Recent studies have demonstrated that the production of reactive
      oxygen species (ROS) itself plays an indispensable role in the process of
      differentiation in various tissues. However, it is unclear whether ROS have an
      effect on the differentiation of keratinocytes essential for the development of
      the epidermal permeability barrier. OBJECTIVE: The aim of the study is to
      determine a major H2O2-generating source by ionomycin in normal human
      keratinocytes (NHKs), and elucidate the physiological role of H2O2 generated by
      identified dual oxidase 1 (DUOX1) on differentiation markers of NHKs. METHODS: To
      detect H2O2 level generated by ionomycin in NHKs, luminal-HRP assays are
      performed. To examine the effects of DUOX1 on differentiation markers of NHKs,
      analysis of Q-RT-PCR, siRNA knockdown, and Western blot analysis were performed.
      RESULTS: We found that levels of H2O2 generated by ionomycin, a Ca(2+) signal
      inducer, showed Ca(2+) dependence manner. In addition, DPI, an inhibitor of
      NOXes, significantly reversed the ionomycin-induced H2O2 level, and inhibited the
      mRNA expression levels of keratin 1, keratin 10, and filaggrin compared with
      other ROS generating system inhibitors. Interestingly, we demonstrated that
      extracellular Ca(2+) markedly up-regulated mRNA expression levels of DUOX1 among
      NADPH oxidase (NOX) isoforms. Knockdown of DUOX1 by RNA interference (RNAi) in
      NHKs significantly antagonized an increase of ionomycin-induced H2O2 level, and
      specifically decreased the expressions of several keratinocyte differentiation
      markers such as keratin 1, transglutaminase 3, desmoglein 1, and aquaporin 9. In
      addition, we also found that formation of cornified envelope was significantly
      reduced in DUOX1-knockdown NHKs. CONCLUSION: These results suggest that DUOX1 is
      the major H2O2-producing source in NHKs stimulated with Ca(2+), and plays a
      significant role in regulating the expression of specific markers necessary for
      the normal differentiation of keratinocytes.

PMID- 24332817
TI  - Participation rate or informed choice? Rethinking the European key performance
      indicators for mammography screening.
AB  - Despite the intensive controversies about the likelihood of benefits and harms of
      mammography screening almost all experts conclude that the choice to screen or
      not to screen needs to be made by the individual patient who is adequately
      informed. However, the "European guideline for quality assurance in breast cancer
      screening and diagnosis" specifies a participation rate of 70% as the key
      performance indicator for mammography screening. This paper argues that neither
      the existing evidence on benefits and harms, nor survey research with women, nor
      compliance rates in clinical trials, nor cost-effectiveness ratios justify
      participation rates as a reasonable performance indicator for preference
      sensitive condition such as mammography screening. In contrast, an informed
      choice rate would be more reasonable. Further research needs to address the
      practical challenges in assessing informed choice rates.

PMID- 24332818
TI  - [Tobacco use by adolescents in Barcelona (Spain) and trends in the last 20
      years].
AB  - OBJECTIVES: Smoking is a preventable cause of early death and the habit starts in
      adolescence. The aim of this study was to describe tobacco consumption in
      secondary school students in 2008 and trends in the last 20 years in Barcelona.
      MATERIAL AND METHODS: We analyzed the trend in tobacco consumption by comparing
      data from 8 surveys carried out between 1987 and 2008 in the 8th (2nd year of
      Compulsory Secondary Education), 10th (4th year of Compulsory Secondary
      Education) and 12th (2nd year of Compulsory Secondary Education) years of
      secondary school. The FRESC questionnaire was used. Data on regular and daily
      consumption and associated factors in 2008 were gathered and compared with those
      corresponding to the previous studies. Percentages of annual change were
      calculated with Joinpoint regression and data were stratified by sex and year of
      education. RESULTS: In 2008, 6.1% of boys and 4.5% of girls in the 8th year,
      15.8% and 20.4% of those in the 10th year, respectively, and 26.1% and 33.1% of
      those in the 12th year, respectively, were regular smokers. A strong association
      was noted between regular smoking and cannabis consumption in three school years,
      as well as with having friends who were smokers and poor school performance. At
      15-16 years old, the average annual decrease from 1996 to 2008 was 6.8% in girls
      and 6.1% in boys. CONCLUSIONS: Adolescent smoking has been decreasing in the last
      few years in Barcelona. There is a strong association between tobacco use and
      cannabis consumption.

PMID- 24332819
TI  - A crisis in confidence: a combined challenge and opportunity for medical imaging
      providers.

PMID- 24332820
TI  - Association between postnatal dexamethasone for treatment of bronchopulmonary
      dysplasia and brain volumes at adolescence in infants born very preterm.
AB  - OBJECTIVES: To compare brain volumes in adolescents who were born extremely
      preterm (<28 weeks gestation) who had received postnatal dexamethasone, and to
      determine if there was a postnatal dexamethasone dose-response effect on brain
      volumes. STUDY DESIGN: Geographical cohort study of extremely preterm adolescents
      born in 1991-1992 in Victoria, Australia. T1-weighted magnetic resonance imaging
      was performed at 18 years of age. Segmented and parcellated brain volumes were
      calculated using an automated segmentation method (FreeSurfer) and compared
      between groups, with and without adjustment for potential confounders. The
      relationships between total postnatal dexamethasone dose and brain volumes were
      explored using linear regression. RESULTS: Of the 148 extremely preterm
      participants, 55 (37%) had received postnatal dexamethasone, with a cumulative
      mean dose of 7.7 mg/kg. Compared with participants who did not receive postnatal
      dexamethasone, those who did had smaller total brain tissue volumes (mean
      difference -3.6%, 95% CI [-7.0%, -0.3%], P value = .04) and smaller white matter,
      thalami, and basal ganglia volumes (all P < .05). There was a trend of smaller
      total brain and white matter volumes with increasing dose of postnatal
      dexamethasone (regression coefficient -7.7 [95% CI -16.2, 0.8] and -3.2 [-6.6,
      0.2], respectively). CONCLUSIONS: Extremely preterm adolescents who received
      postnatal dexamethasone in the newborn period had smaller total brain tissue
      volumes than those who did not receive postnatal dexamethasone, particularly
      white matter, thalami, and basal ganglia. Vulnerability of brain tissues or
      structures associated with postnatal dexamethasone varies by structure and
      persists into adolescence.

PMID- 24332822
TI  - Prevalence of functional gastrointestinal disorders in Colombian school children.
AB  - OBJECTIVES: To determine prevalence for functional gastrointestinal disorders
      (FGIDs) in Colombian school children using the Questionnaire on Pediatric
      Gastrointestinal Symptoms-Rome III Version (QPGS-III) and to determine possible
      risk factors. STUDY DESIGN: The QPGS-III was translated into Spanish then reverse
      translated by a team of bilingual physicians. Focus groups of Colombian children
      were conducted to assure understanding of the Spanish version. Children at 1
      public school and 2 private schools in Pasto, Colombia were invited to
      participate in a prevalence study using the translated questionnaire. RESULTS: A
      total of 373 children (95 private school, 278 public school), with mean age 9.9
      years completed the QPGS-III. Twenty-nine percent of children were diagnosed with
      FGIDs. FGIDs were more common in females (OR, 1.63; 95% CI, 1.04-2.56).
      Functional constipation (14%) was the most common FGID. Irritable bowel syndrome
      was the most common abdominal pain-related FGID (5.4%). Abdominal migraine (1%)
      and cyclic vomiting syndrome (0.3%) were the least common FGIDs. CONCLUSION:
      FGIDs are common in Colombian school children.

PMID- 24332823
TI  - Mechanical ventilation and thoracic artificial lung assistance during mechanical
      circulatory support with PUCA pump: in silico study.
AB  - Patients assisted with left ventricular assist device (LVAD) may require
      prolonged mechanical ventilatory assistance secondary to postoperative
      respiratory failure. The goal of this work is the study of the interdependent
      effects LVAD like pulsatile catheter (PUCA) pump and mechanical ventilatory
      support or thoracic artificial lung (TAL), by the hemodynamic point of view,
      using a numerical simulator of the human cardiovascular system. In the simulator,
      different circulatory sections are described using lumped parameter models.
      Lumped parameter models have been designed to describe the hydrodynamic behavior
      of both PUCA pump and thoracic artificial lung. Ventricular behavior atrial and
      septum functions were reproduced using variable elastance model. Starting from
      simulated pathological conditions we studied the effects produced on some
      hemodynamic variables by simultaneous PUCA pump, thoracic artificial lung or
      mechanical ventilation assistance. Thoracic artificial lung was applied in
      parallel or in hybrid mode. The effects of mechanical ventilation have been
      simulated by changing mean intrathoracic pressure value from -4 mmHg to +5 mmHg.
      The hemodynamic variables observed during the simulations, in different assisted
      conditions, were: left and right ventricular end systolic (diastolic) volume,
      systolic/diastolic aortic pressure, mean pulmonary arterial pressure, left and
      right mean atrial pressure, mean systemic venous pressure and the total blood
      flow. Results show that the application of PUCA (without mechanical ventilatory
      assistance) increases the total blood flow, reduces the left ventricular end
      systolic volume and increases the diastolic aortic pressure. Parallel TAL
      assistance increases the right ventricular end diastolic (systolic) volume
      reduction both when PUCA is switched "ON" and both when PUCA is switched "OFF".
      By switching "OFF" the PUCA pump, it seems that parallel thoracic artificial lung
      assistance produces a greater cardiac output (respect to hybrid TAL assistance).
      Results concerning PUCA and TAL interaction produced by simulations cannot be
      compared with "in vivo" results since they are not presented in literature. But
      results concerning the effects produced by LVAD and mechanical ventilation have a
      trend consistent with those presented in literature.

PMID- 24332821
TI  - Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes
      in newborns receiving hypothermia therapy.
AB  - OBJECTIVE: To evaluate serum neuronal and inflammatory biomarkers to determine
      whether measurements of umbilical cords at birth can stratify severity of hypoxic
      ischemic encephalopathy (HIE), whether serial measurements differ with
      hypothermia-rewarming, and whether biomarkers correlate with neurological
      outcomes. STUDY DESIGN: This is a prospective cohort of inborn term newborns with
      varying degrees of HIE by neurological assessment. Neuronal glial fibrillary
      acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and inflammatory
      cytokines were measured in serum from umbilical artery at 6-24, 48, 72, and 78
      hours of age. Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler
      Development-III scales) were performed at 15-18 months. RESULTS: Twenty neonates
      had moderate (n = 17) or severe (n = 3) HIE and received hypothermia; 7 had mild
      HIE and were not cooled. At birth, serum GFAP and ubiquitin carboxyl-terminal
      hydrolase L1 increased with the severity of HIE (P < .001), and serial GFAP
      remained elevated in neonates with moderate to severe HIE. Interleukin (IL)-6, IL
      8, and vascular endothelial growth factor were greater at 6-24 hours in moderate
      to severe vs mild HIE (P < .05). The serial values were unaffected by hypothermia
      rewarming. Elevated GFAP, IL-1, IL-6, IL-8, tumor necrosis factor, interferon,
      and vascular endothelial growth factor at 6-24 hours were associated with
      abnormal neurological outcomes. CONCLUSIONS: The severity of the hypoxic-ischemic
      injury can be stratified at birth because elevated neuronal biomarkers in cord
      serum correlated with severity of HIE and outcomes.

PMID- 24332824
TI  - Applying hierarchical task analysis to improving the patient positioning for
      direct lateral interbody fusion in spinal surgery.
AB  - The present study brings together for the first time the techniques of
      hierarchical task analysis (HTA), human error identification (HEI), and business
      process management (BPM) to select practices that can eliminate or reduce
      potential errors in a surgical setting. We applied the above approaches to the
      improvement of the patient positioning process for lumbar spine surgery referred
      to as 'direct lateral interbody fusion' (DLIF). Observations were conducted to
      gain knowledge on current DLIF positioning practices, and an HTA was constructed.
      Potential errors associated with the practices specific to DLIF patient
      positioning were identified. Based on literature review and expert views
      alternative practices are proposed aimed at improving the DLIF patient
      positioning process. To our knowledge, this is the first attempt to use BPM in
      association with HEI/HTA for the purpose of improving the performance and safety
      of a surgical process - with promising results.

PMID- 24332825
TI  - Comparison of subjective comfort ratings between anatomically shaped and
      cylindrical handles.
AB  - Most authors have provided diameter recommendations for cylindrical handle design
      in order to increase performance, avoid discomfort, and reduce the risk of
      cumulative trauma disorders. None of the studies has investigated the importance
      of determining the correct handle shape on the subjective comfort ratings, which
      could further improve the handles' ergonomics. Therefore, new methods based on a
      virtual hand model in its optimal power grasp posture have been developed in
      order to obtain customised handles with best fits for targeted subjects.
      Cylindrical and anatomically shaped handles were evaluated covering ten subjects
      by means of an extensive subjective comfort questionnaire. The results suggest
      large impact of the handle shape on the perceived subjective comfort ratings.
      Anatomically shaped handles were rated as being considerably more comfortable
      than cylindrical handles for almost all the subjective comfort predictors. They
      showed that handle shapes based on optimal power grasp postures can improve
      subjective comfort ratings, thus maximising performance. Future research should
      consider real conditions, since the comfort ratings can vary based on the
      specific task and by the tool selected for the task. 

PMID- 24332826
TI  - The effects of transfer distance on spine kinematics when placing boxes at
      different heights.
AB  - Twisting and lateral bending motions in repetitive lifting tasks are associated
      with occupational low back injuries and can be challenging to reduce with
      engineering controls. This study tested the hypothesis that twisting and lateral
      bending can be reduced by changing the transfer distance. Eighteen males, with no
      material handling experience lifted 10.9 kg boxes from 0.9 m above the floor and
      placed the boxes at a destination located 0.50, 0.75, 1.00, 1.25, 1.50, or 1.75 m
      away and at heights of 0.5 m, 0.9 m, and 1.3 m above the floor. Overall, twisting
      and forward bending decreased with increased transfer distance when placing the
      box. Conversely, the lateral bending when lifting and placing the box increased
      with increasing transfer distance. In short, having a transfer distance between 1
      and 1.25 m when performing palletizing tasks to different heights may optimally
      balance spine kinematics, back injury risk, and productivity measures.

PMID- 24332827
TI  - Characterization of the in vitro core surface proteome of Mycoplasma mycoides
      subsp. mycoides, the causative agent of contagious bovine pleuropneumonia.
AB  - Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp.
      mycoides (Mmm) is a severe cattle disease, present in many countries in sub
      Saharan Africa. The development of improved diagnostic tests and vaccines for
      CBPP control remains a research priority. Polyacrylamide gel electrophoresis and
      mass spectrometry were used to characterize the Triton X-114 soluble proteome of
      nine Mmm strains isolated from Europe or Africa. Of a total of 250 proteins
      detected, 67 were present in all strains investigated. Of these, 44 were
      predicted to be lipoproteins or cytoplasmic membrane-associated proteins and are
      thus likely to be members of the core in vitro surface membrane-associated
      proteome of Mmm. Moreover, the presence of all identified proteins in other
      ruminant Mycoplasma pathogens were investigated. Two proteins of the core
      proteome were identified only in other cattle pathogens of the genus Mycoplasma
      pointing towards a role in host-pathogen interactions. The data generated will
      facilitate the identification and prioritization of candidate Mycoplasma antigens
      for improved control measures, as it is likely that surface-exposed membrane
      proteins will include those that are involved in host-pathogen interactions. 

PMID- 24332829
TI  - "Brachyspira hampsonii" clade I isolated from Belgian pigs imported to Germany.
AB  - This report describes the detection of "Brachyspira (B.) hampsonii" clade I in
      Belgian pigs imported to Germany. Two of seventeen pigs from one herd were
      reported positive for Brachyspira hyodysenteriae by culture in a Belgian
      diagnostic laboratory, but negative for this Brachyspira species by specific PCR.
      In this study, from 22 fecal samples and 2 colon contents of these animals
      various Brachyspira species were cultured and identified by nox-RFLP as
      Brachyspira murdochii, Brachyspira innocens and Brachyspira intermedia. Albeit
      the six B. intermedia isolates proved to be negative in a species specific PCR.
      Sequencing of the nox-gene of three of these isolates revealed that the sequences
      were 99% identical to published sequences of "B. hampsonii" clade I. From one pig
      which was positive for "B. hampsonii" clade I histopathology was done and showed
      moderate lesions consistent with brachyspiral disease. 

PMID- 24332828
TI  - Molecular genetic analysis of Dichelobacter nodosus proteases AprV2/B2, AprV5/B5
      and BprV/B in clinical material from European sheep flocks.
AB  - Dichelobacter nodosus, the etiological agent of ovine footrot, exists both as
      virulent and as benign strains, which differ in virulence mainly due to subtle
      differences in the three subtilisin-like proteases AprV2, AprV5 and BprV found in
      virulent, and AprB2, AprB5 and BprB in benign strains of D. nodosus. Our
      objective was a molecular genetic epidemiological analysis of the genes of these
      proteases by direct sequence analysis from clinical material of sheep from herds
      with and without history of footrot from 4 different European countries. The data
      reveal the two proteases known as virulent AprV2 and benign AprB2 to correlate
      fully to the clinical status of the individuals or the footrot history of the
      herd. In samples taken from affected herds, the aprV2 gene was found as a single
      allele whereas in samples from unaffected herds several alleles with minor
      modifications of the aprB2 gene were detected. The different alleles of aprB2
      were related to the herds. The aprV5 and aprB5 genes were found in the form of
      several alleles scattered without distinction between affected and non-affected
      herds. However, all different alleles of aprV5 and aprB5 encode the same amino
      acid sequences, indicating the existence of a single protease isoenzyme 5 in both
      benign and virulent strains. The genes of the basic proteases BprV and BprB also
      exist as various alleles. However, differences found in samples from affected
      versus non-affected herds do not reflect the currently known epitopes that are
      attributed to differences in biochemical activity. The data of the study confirm
      the prominent role of AprV2 in the virulence of D. nodosus and shed a new light
      on the presence of the other protease genes and their allelic variants in
      clinical samples. 

PMID- 24332831
TI  - Is formal decompression necessary for parameniscal cysts associated with meniscal
      tears?
AB  - BACKGROUND: Meniscal tears and associated parameniscal cysts have good outcomes
      after partial meniscectomy and cyst evacuation. Good outcomes have been noted
      after partial meniscectomy with recurrent cysts. This investigation asks if
      partial meniscectomy without meniscal cyst decompression is sufficient for
      positive patient outcome. METHODS: Sixteen patients treated between 2005 and 2010
      for a meniscal cyst and concomitant meniscal tear. Inclusion criteria were
      meniscal tear and parameniscal cyst per MRI, no prior surgery on the affected
      knee, and Outerbridge classification of I/II. Two patients were excluded.
      Fourteen patients completed the study until final follow-up. Lysholm knee scores
      were documented at 6 months post-operatively and at final follow-up. Re
      evaluation or second surgery of the treated knee was documented. RESULTS: Eight
      lateral cysts and six medial cysts were diagnosed. Eight cysts were associated
      with a horizontal cleavage tear, while six menisci had a complex tear with a
      horizontal cleavage component. The average cyst size was 1.3 cm (0.5 to 3.5) at
      the largest diameter. At 6 months, the average Lysholm knee score was 94.1. At
      mean 5 years, the average score was 89.1. Patients with medial cysts, cysts
      greater than 1.0 cm, horizontal cleavage tears, or without simultaneous
      chondroplasty scored higher in the short and medium-term than their respective
      counterparts. CONCLUSIONS: Excellent short and medium-term outcomes can be
      achieved following partial meniscectomy without cyst decompression for patients
      with meniscal cysts and associated meniscal tears. LEVEL OF EVIDENCE: Level IV.

PMID- 24332830
TI  - A population-based cohort study on chronic obstructive pulmonary disease in Latin
      America: methods and preliminary results. The PLATINO Study Phase II.
AB  - BACKGROUND: The PLATINO baseline study, conducted from 2003-2005 in five Latin
      American cities (Sao Paulo, Mexico City, Montevideo, Santiago, Caracas), showed a
      high prevalence of chronic obstructive pulmonary disease (COPD). METHODS/DESIGN:
      A follow-up study was conducted in three out of the five centers (Montevideo,
      Santiago, and Sao Paulo) after a period of 5, 6 and 9years, respectively, aimed
      at verifying the stability of the COPD diagnosis over time, the evolution of the
      disease in terms of survival, morbidity and respiratory function, and the
      analyses of inflammatory and genetic biomarkers in the blood. Some questions were
      added to the original questionnaire and death certificates were obtained from the
      national official registries. RESULTS: The fieldwork has been concluded in the
      three centers. From the original samples in the PLATINO study phasei, we were
      able to locate and interview 85.6% of patients in Montevideo, 84.7% in Santiago
      and 77.7% in Sao Paulo. Individuals who could not be located had higher education
      levels in Brazil, and were more likely to be current smokers in Santiago and Sao
      Paulo than in Montevideo. The overall quality of spirometries was >=80% according
      to American Thoracic Society criteria. The number of deaths was 71 (Montevideo),
      95 (Santiago) and 135 (Sao Paulo), with death certificates obtained from the
      national mortality registries for 76.1%, 88.3% and 91.8% of cases in Montevideo,
      Santiago and Sao Paulo, respectively. CONCLUSIONS: This study shows that is
      possible to perform population-based longitudinal studies in Latin American with
      high follow-up rates and high-quality spirometry data. The adequacy of national
      mortality registries varies among centers in Latin America.

PMID- 24332832
TI  - Lower impulsive loadings following intensive weight loss after bariatric surgery
      in level and stair walking: a preliminary study.
AB  - BACKGROUND: There are currently very few of studies which have evaluated the role
      of bariatric surgery in joint loadings and changes in gait. We wanted to examine
      how impulsive loading would change level and stair walking in severely or
      morbidly obese subjects after they had undergone bariatric surgery and weight
      loss. METHODS: Thirteen female and three male adults aged between 30 and 63
      years, cleared for Roux-en-Y gastric bypass, were recruited into this study. All
      subjects were severely or morbidly obese i.e., body mass index was >35 kg/m(2).
      The measurement methods consisted of triaxial skin mounted accelerometers and
      ground reaction force (GRF); conducted at two different predetermined gait
      speeds. RESULTS: The average weight loss was 27.4 (SD8.7) kg after 8.8 (SD3.9)
      months of follow-up period. Most of the absolute GRF parameters decreased in
      proportion to weight loss. However, medio-lateral GRF parameters decreased more
      than expected. The general trend in the knee accelerations demonstrated lower
      impulsive loadings in both axial and horizontal directions after weight loss. We
      did not observe any significant changes in stair walking. CONCLUSIONS: Weight
      loss after bariatric surgery not only induces a simple mass-related adaptation in
      gait but also achieves mechanical plasticity in gait strategy.

PMID- 24332833
TI  - A retrospective study of daptomycin use in a Paris teaching-hospital.
AB  - OBJECTIVE: We retrospectively studied daptomycin use during 2010 at the Bichat
      Claude-Bernard teaching-hospital (Paris) to observe the evolution of daptomycin
      prescriptions. PATIENTS AND METHODS: Twenty-one patients were included and
      several parameters were documented: site of infection, bacterial species
      involved, reason for daptomycin use, dose and clinical outcome. RESULTS: Ninety
      five percent of daptomycin prescritions were off-label and most did not comply
      with local guidelines. Fifteen of the 21 patients were cured (71%), including 9
      patients of the 12 with off-label and off-local recommendation prescriptions
      (75%). Osteitis and Enterococcus spp endocarditis were the new indications.
      Daptomycin was increasingly used at higher doses: 52% of our patients were given
      doses above 6mg/kg. Staphylococcus spp. was the most frequent pathogen
      responsible for infection is our patients, followed by Enterococcus spp.
      CONCLUSION: Daptomycin use is likely to evolve because of its effectiveness in
      the treatment of osteitis, left-sided and Enterococcus spp. infective
      endocarditis. It is generally used at higher doses, which are well tolerated.
      However, therapeutic monitoring needs to be developed. The antibiotic commission
      of our hospital gave new recommendations for daptomycin use in 2011.

PMID- 24332834
TI  - [Effectiveness of an educational program for reducing blood culture
      contamination].
AB  - INTRODUCTION: Blood culture contaminations can lead to unnecessary diagnostic
      procedures and treatments, increasing workload, length of stay, and costs.
      OBJETIVES: Development of an educational program to reduce contamination rates.
      MATERIAL AND METHODS: Our study compared contamination rates (CR) between a pre
      intervention period (Ppre) and post-intervention period (Ppos), where clinical
      charts from patients with positive blood cultures were reviewed. Intervention
      consisted of a questionnaire where knowledge of blood culture practice and its
      significance was assessed. Results are discussed and explained. RESULTS: A
      presentation on blood culture guidelines was discussed in every nurse station.
      There was a median of 64% (40.8-78.5) attendance rate. The median of correct
      answers was 69% in the Ppre (54.1-83.3) with 85.7% (83.3-100) in the Ppos,
      indicating an improvement in 85.7% of the departments that could be compared.
      There were 136 (4.2%) contaminants in the Ppre and 186 (6.05%) in the Ppos
      (P=.005). Among the different departments the average of CR varied from 5% vs
      7.5% (P=.79) between 2011 and 2012. Only 2 departments reduced CR by 2% to 2.5%,
      the difference was not significant. CONCLUSIONS: The intervention failed to
      reduce overall contamination rates, but knowledge of blood culture practice
      improved. Our results identified the errors that will help us to design a
      successful approach in future follow-up programs.

PMID- 24332835
TI  - [Analysis of the variability of the selection criteria of statutory nursing staff
      in Spanish autonomous communities].
AB  - AIM: To determine the general and specific conditions required in the official
      announcements of the different autonomous health services for the provision of
      vacant nursing positions as statutory nursing staff. METHOD: A documentary review
      of the latest public employment offers (PEO) for statutory nursing staff of the
      17 Spanish autonomous communities (AACC) was carried out, between June 2007 and
      August 2012. The variables related to the announcements method, the general
      requirements and the criteria used to evaluate the applicants, were reviewed.
      RESULTS: All AACC use the public competition as the method for selecting
      applicants. The general requirements are uniform in the 17 official
      announcements. The most commonly used system today in the public competition is
      the multiple-choice test (58%), being necessary to obtain at least 50% of the
      marks to pass in all of them. At the public competition stage, the undergraduate,
      specialized and continuous education; professional experience, scientific,
      teaching activities and other merits are evaluated differently. The knowledge of
      the regional language is present in official announcements. The weight of the
      parts involved in the process is variable, with 50-50% and 60-40% being the most
      commonly used. CONCLUSIONS: The general requirements that the applicants should
      meet are homogeneous, as well as the types of PEO. The competition processes of
      the AACC are very different from each other, and there is a great variability of
      criteria in the selection process based on the evaluation of the suitable merits,
      and the importance that each stage has on the competition.

PMID- 24332836
TI  - Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration.
AB  - The intestinal epithelium continually self-renews and can rapidly regenerate
      after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs).
      Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+)
      cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC populations
      are thought to play a similar role during intestinal regeneration following
      radiation-induced damage. We tested this regeneration hypothesis by combining
      depletion of Lgr5(+) ISCs with radiation exposure. In contrast to the negligible
      effect of Lgr5(+) ISC loss during homeostasis, depletion of Lgr5(+) cells during
      radiation-induced damage and subsequent repair caused catastrophic crypt loss and
      deterioration of crypt-villus architecture. Interestingly though, we found that
      crypts deficient for Lgr5(+) cells are competent to undergo hyperplasia upon loss
      of Apc. These data argue that Lgr5(-) reserve stem cells are radiosensitive and
      that Lgr5(+) cells are crucial for robust intestinal regeneration following
      radiation exposure but are dispensable for premalignant hyperproliferation. 

PMID- 24332837
TI  - Redefining the in vivo origin of metanephric nephron progenitors enables
      generation of complex kidney structures from pluripotent stem cells.
AB  - Recapitulating three-dimensional (3D) structures of complex organs, such as the
      kidney, from pluripotent stem cells (PSCs) is a major challenge. Here, we define
      the developmental origins of the metanephric mesenchyme (MM), which generates
      most kidney components. Unexpectedly, we find that posteriorly located T(+) MM
      precursors are developmentally distinct from Osr1(+) ureteric bud progenitors
      during the postgastrulation stage, and we identify phasic Wnt stimulation and
      stage-specific growth factor addition as molecular cues that promote their
      development into the MM. We then use this information to derive MM from PSCs.
      These progenitors reconstitute the 3D structures of the kidney in vitro,
      including glomeruli with podocytes and renal tubules with proximal and distal
      regions and clear lumina. Furthermore, the glomeruli are efficiently vascularized
      upon transplantation. Thus, by reevaluating the developmental origins of
      metanephric progenitors, we have provided key insights into kidney specification
      in vivo and taken important steps toward kidney organogenesis in vitro.

PMID- 24332838
TI  - [Lifestyles related with cardiovascular risk in university students].
AB  - OBJECTIVE: To analyze the lifestyles associated with cardiovascular risk in a
      university population in university admission. MATERIAL AND METHODS: A
      descriptive, observational, cross-sectional students of the Catholic University
      San Antonio of Murcia. Select a sample of 672 college students enrolled in the
      first year of the race. The instrument used to collect the data, is a self
      completed questionnaire anonymous, with a total of 59 questions. RESULTS: With
      respect to smoking 242 are smokers (36%), 117 former smokers (17.4%), and 313 non
      smokers (46.6%). When compared snuff consumption by sex, no differences are
      detected. By running the largest group of non-smokers often seen in students of
      physical sciences (59.1%) compared to the careers humanities (40.9%). 87.4% (587)
      of students surveyed report using alcohol, compared to 12.6% (85) no. According
      to the race group not detected association between race group and the fact
      consume alcohol or not. The 65.6% of students surveyed physical exercise commonly
      referred, being higher the frequency of exercise in men than in women (81.7%
      versus 49.4%) (P<.001). 54.3% of surveyed students follow a dietary pattern
      typical of the Mediterranean diet. CONCLUSIONS: The University does not exercise
      the role that could mean in terms of enhancing healthy lifestyles and abandonment
      of harmful health styles.

PMID- 24332839
TI  - Changes in spectral power of fetal heart rate variability in small-for
      gestational-age fetuses are associated with fetal sex.
AB  - BACKGROUND: Little is known about the influences of fetal weight and sex on
      spectral analysis of fetal heart rate (FHR) variability. AIM: The study aims to
      assess whether there are differences in spectral power of FHR variability
      according to fetal weight and sex during labor. STUDY DESIGN: Case-control study.
      A total of 414 singleton term deliveries without fetal acidemia were divided into
      small-for-gestational-age (SGA) (n=29) and non-SGA (n=385) groups. Analyses were
      performed separately according to fetal sex. SUBJECTS: FHR recordings obtained
      with cardiotocography during the last 2h of labor preceding delivery. OUTCOME
      MEASURES: Our outcome measures include spectral power of FHR variability.
      RESULTS: For the male group, SGA fetuses had significantly lower values for low,
      movement, high, and total frequencies of spectral power compared with non-SGA
      fetuses (all P<0.005). Normalized low frequency (LFn) was significantly higher,
      and normalized high frequency (HFn) was significantly lower in SGA fetuses
      compared with non-SGA fetuses (all P<0.005). In contrast, for the female group,
      there were no significant differences in any of the indices of spectral power
      between the SGA and non-SGA fetuses. In addition, SGA males had significantly
      higher LFn spectral power and lower HFn spectral power compared to SGA females
      (P=0.016, and 0.041, respectively). CONCLUSIONS: SGA males have decreased
      spectral power of FHR variability compared with non-SGA males during labor.
      However, there are no differences between SGA and non-SGA female fetuses. It is
      important in the clinical setting to take fetal weight and sex into account
      during FHR monitoring using spectral analysis.

PMID- 24332840
TI  - Telaprevir is a substrate and moderate inhibitor of P-glycoprotein, a strong
      inductor of ABCG2, but not an activator of PXR in vitro.
AB  - Triple therapy combining the protease inhibitor telaprevir with interferon-alpha
      and ribavirin is a promising new option for long-term treatment of hepatitis C.
      The interaction potential of telaprevir has not yet been fully elucidated. The in
      vitro potency of telaprevir to inhibit P-glycoprotein (P-gp, ABCB1) and breast
      cancer resistance protein (BCRP, ABCG2) was assessed and its substrate
      characteristics for P-gp, BCRP and the multidrug resistance-associated proteins
      (MRPs, ABCCs) 1-3 were evaluated. The inducing properties of telaprevir on
      important drug-metabolising enzymes and transporters were also assessed and its
      ability to activate the pregnane X receptor (PXR) was investigated. Using growth
      inhibition assays, it was confirmed that telaprevir is a substrate of P-gp and it
      was demonstrated for the first time that it is not transported by BCRP and MRPs.
      Telaprevir only moderately inhibited P-gp in the calcein assay and did not
      inhibit BCRP in the pheophorbide A assay. In LS180 cells, telaprevir strongly
      induced mRNA expression of ABCG2 (4.3-fold at 30 MUmol/L) and weakly induced
      ABCB11, CYP2C19 and UGT1A3. In contrast, telaprevir had no significant influence
      on mRNA expression of CYP3A4, UGT1A9, ABCB1, ABCC2 and SLCO1B1. In a reporter
      gene assay, telaprevir did not activate PXR. Thus, it appears unlikely that
      telaprevir induces CYP3A4 and P-gp in vivo in such a way as to provoke clinically
      relevant drug interactions. From the numerous perpetrator characteristics,
      telaprevir's inhibitor properties, especially of CYP3A4 and P-gp, appear to be
      the most relevant mechanism for drug interactions. The clinical relevance of the
      strong inducing effects on ABCG2 requires proper assessment.

PMID- 24332841
TI  - Long term outcome for the tiniest or most immature babies.

PMID- 24332842
TI  - Is very preterm birth a risk factor for adult cardiometabolic disease?
AB  - The first infants to experience modern pre- and neonatal care are now in their
      thirties, an age at which the incidence of cardiometabolic disease is low.
      However, data from cohorts born preterm prior to the introduction of modern care
      suggest an increased risk of type 2 diabetes. For young adult cohorts of former
      very small or very preterm infants, there is accumulating evidence of increased
      risk factors for later cardiovascular disease, including higher blood pressure,
      lower lean body mass, impaired glucose regulation, and perhaps a more atherogenic
      lipid profile. Regarding lifestyle, adults born very small or very preterm
      undertake less non-conditioning physical activity and may have a lower intake of
      fruit and milk products. Any intervention reducing risk factors, in particular
      blood pressure and low physical activity, would have a substantial potential to
      reduce the lifetime disease burden in small preterm infants. There are now enough
      data to warrant an expert evaluation of the level of evidence for cardiometabolic
      disease in individuals born very small or very preterm, which has possible public
      health implications. 

PMID- 24332844
TI  - [Analysis of constipation in severe trauma patients].
AB  - OBJECTIVES: To evaluate the incidence and risk factors of constipation in
      patients with severe trauma (ST). MATERIALS AND METHOD: A retrospective
      observational study (January-December 2011) of medical records in ST-patients
      with a minimum stay of 5 days was performed. Descriptive analysis of variables,
      inferential analysis: Student's T test and Chi-square of SPSS 17.0. Significance
      level P<.05. RESULTS: A total of 80 patients fulfilled the inclusion criteria,
      but only 69 could be analyzed. Of these, 84.06% showed constipation (according to
      its definition by the Work Group for Metabolism and Nutrition SEMICYUC). The most
      frequent day of first stool was day 7 and 9 after tolerance of enteral nutrition.
      Statistical significance (S.S.) of constipation was found with stay, days of
      sedation/relaxation/opiates, and mechanical ventilation. There was no S.S.
      between early enteral nutrition (EEN) and constipation (P>.05). CONCLUSIONS:
      There is a very high incidence of constipation in ST patients. ICU stay, days of
      analgesic sedation, relaxation, and mechanical ventilation are risk factors that
      influence the occurrence of this problem. Laxatives should be prescribed
      prophylactically.

PMID- 24332845
TI  - [Innovations in continuing/permanent education methods for the intensive care
      nurses].
AB  - Intensive care nursing is carried out in a dynamic environment characterized by
      the continuous incorporation of new technologies, approaches to care and a
      request for safety, participation and transparency by the public.
      Continuing/permanent intensive care nursing training in the acquisition of new
      competencies is key in this setting. In order to achieve this goal, simulation
      and problem based learning should be incorporated as essential methodologies to
      teach these skills. At the same time research should be done on which attitudes,
      competences, and knowledge are necessary to increase their intellectual
      knowledge. The core characteristics of ICU and its nursing should allow a deep
      change in their approach to continuing/permanent nursing education. 

PMID- 24332843
TI  - Low hemoglobin deferral in blood donors.
AB  - Low hemoglobin deferral occurs in about 10% of attempted whole blood donations
      and commonly is a consequence of iron deficiency anemia. Pre-menopausal women
      often have iron deficiency anemia caused by menstruation and pregnancy and have
      low hemoglobin deferral on their first donation attempt. Frequent donors also
      develop iron deficiency and iron deficiency anemia because blood donation removes
      a large amount of iron from the donor and the 56-day minimum inter-donation
      interval for donors in the United States is not sufficient for recovery of
      hemoglobin and iron stores. Other causes for low hemoglobin deferral range from a
      medically insignificant deferral of a woman with hemoglobin between 12.0 and 12.4
      g/dL, which is within the normal reference range but below the 12.5 g/dL needed
      to donate blood, to anemia caused by an unrecognized malignancy in a "healthy"
      individual attempting to donate blood. The diverse causes of anemia in blood
      donors make it difficult to provide accurate information to donors about the
      cause of their low hemoglobin deferral and complicate implementation of programs
      to prevent them by blood collecting agencies. This article reviews how hemoglobin
      is measured and the demographics and causes of low hemoglobin deferral in blood
      donors. It provides recommendations for how blood collection agencies can provide
      donors with accurate information about the cause of their deferral and discusses
      programs that can be implemented to decrease these deferrals in regular donors. 

PMID- 24332846
TI  - [Evaluation of immediate post-operative pain in heart surgery using the
      Behavioural Pain Scale].
AB  - INTRODUCTION: Patients in the immediate postoperative period of cardiac surgery
      have abolished communication skills and therefore can not express pain. Pain
      produces significant adverse effects that alter the patients' course. Therefore,
      identifying and controlling them will lead to increased quality of care for the
      critical patient. OBJECTIVE: To measure the degree of pain in patients in the
      immediate postoperative period of cardiac surgery by scaling Behavioural Pain
      Scale. MATERIAL AND METHOD: An observational, prospective and longitudinal.
      Patients over 18 years in the first 24 hours of admission with no communication
      problems who were under sedation and subjected to mechanical ventilation were
      included. Twenty patients were enrolled in the study. The Behavioural Pain Scale
      (BPS) was used during two procedures usually considered as a painful practice in
      the literature, that is, mobilization and/or postural changes and aspiration of
      secretions. RESULTS: Twenty-seven measurements were made of procedures considered
      as painful. The results obtained by applying the scale BPS showed that 70.4% of
      patients had no pain, 22.2% had mild to moderate pain and 7.4% had unacceptable
      pain. CONCLUSION: This study has identified that the patients suffer pain during
      the postoperative period. Within these patients, there is a small, but not
      insignificant number whose pain is unacceptable during this period. This finding
      serves as a beginning for a line of research to improve the handling of the
      postoperative pain during immediate post-operative cardiac surgery.

PMID- 24332847
TI  - [New devices of fecal diversion and collection: adverse effects described in the
      literature].
AB  - Among products for the management and control of faeces in patients with fecal
      incontinence, there are new devices that allow the diversion and collection of
      fecal matter. This study has aimed to know the complications related to these new
      devices described in the literature. METHOD: A search was made in the main
      bibliographic databases, obtaining publications on the new devices. The relevant
      documents were selected, these being those that described complications. After
      these were described. RESULTS: A total of 13 relevant documents were recovered.
      There were 45 adverse events 36 patients. Those having the greatest incidence
      were rectal bleeding (10 patients) and abdominal distension (6 patients).
      CONCLUSION: In order to provide the best patient care, it is essential to know
      the possible complications in order to be able to prevent them. The cares given
      these patients need to be reevaluated.

PMID- 24332848
TI  - T-wave inversions related to left ventricular basal hypertrophy and myocardial
      fibrosis in non-apical hypertrophic cardiomyopathy: a cardiovascular magnetic
      resonance imaging study.
AB  - OBJECTIVES: To investigate the relationship between T-wave inversions and left
      ventricular (LV) segmental hypertrophy and myocardial fibrosis assessed by
      cardiovascular magnetic resonance (CMR) in patients with non-apical hypertrophic
      cardiomyopathy (HCM). METHODS: 196 consecutive patients with non-apical HCM
      underwent late gadolinium enhancement (LGE) CMR and 12-lead electrocardiogram.
      The distribution and magnitude of LV segmental hypertrophy and LGE were assessed
      according to the AHA 17-segment model and analyzed in relation to T-wave
      inversions. RESULTS: Of 196 HCM patients, 144 (73%) exhibited T-wave inversions.
      144 (73%) patients had evidence of myocardial fibrosis as defined by LGE, and the
      prevalence of LGE was significantly higher in patients with T-wave inversions
      compared with those without T-wave inversions (78% vs. 59%, P=0.008). T-wave
      inversions were related to basal anterior and basal anteroseptal LGE (20% vs.
      10%, P=0.04 and 68% vs. 46%, P=0.005, respectively). In addition, T-wave
      inversions were associated with greater basal anteroseptal and basal inferior
      wall thickness (19.5 +/- 4.7 mm vs. 16.7 +/- 4.5mm, P<0.001 and 10.9 +/- 3.3mm
      vs. 9.6 +/- 3.0mm, P=0.01, respectively). By logistic regression analysis, basal
      anteroseptal wall thickness and LGE were independent determinants of T-wave
      inversions (P=0.005, P=0.01, respectively). CONCLUSIONS: T-wave inversions in HCM
      are associated with LGE and wall thickness of the left ventricular basal
      segments. Moreover, basal anteroseptal wall thickness and LGE are independent
      determinants of T-wave inversions.

PMID- 24332850
TI  - Aging yeast cells undergo a sharp entry into senescence unrelated to the loss of
      mitochondrial membrane potential.
AB  - In budding yeast, a mother cell can produce a finite number of daughter cells
      before it stops dividing and dies. Such entry into senescence is thought to
      result from a progressive decline in physiological function, including a loss of
      mitochondrial membrane potential (DeltaPsi). Here, we developed a microfluidic
      device to monitor the dynamics of cell division and DeltaPsi in real time at
      single-cell resolution. We show that cells do not enter senescence gradually but
      rather undergo an abrupt transition to a slowly dividing state. Moreover, we
      demonstrate that the decline in DeltaPsi, which is observed only in a fraction of
      cells, is not responsible for entry into senescence. Rather, the loss of DeltaPsi
      is an age-independent and heritable process that leads to clonal senescence and
      is therefore incompatible with daughter cell rejuvenation. These results
      emphasize the importance of quantitative single-cell measurements to decipher the
      causes of cellular aging. 

PMID- 24332849
TI  - USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to
      suppress tumor formation.
AB  - The reduced protein expression of SIRT6 tumor suppressor is involved in
      tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation
      in human cancers remain unknown. Using a proteomic approach, we have identified
      the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the
      SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect
      SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional
      activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell
      cycle progression, cancer cell growth, and tumor formation. To support this
      conclusion, we detected significant reductions in both USP10 and SIRT6 protein
      expression in human colon cancers. Our study discovered crosstalk between two
      tumor-suppressive genes in regulating cell-cycle progression and proliferation
      and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6
      degradation. 

PMID- 24332851
TI  - Germline signaling mediates the synergistically prolonged longevity produced by
      double mutations in daf-2 and rsks-1 in C. elegans.
AB  - Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1
      (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin
      (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However,
      it has not been clear how and in which tissues they interact with each other to
      modulate longevity. Here, we demonstrate that a combination of mutations in daf-2
      and rsks-1 produces a nearly 5-fold increase in longevity that is much greater
      than the sum of single mutations. This synergistic lifespan extension requires
      positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein
      kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for
      this synergistic longevity. Moreover, germline-specific inhibition of rsks-1
      activates DAF-16 in the intestine. Together, our findings highlight the
      importance of the germline in the significantly increased longevity produced by
      daf-2 rsks-1, which has important implications for interactions between the two
      major conserved longevity pathways in more complex organisms. 

PMID- 24332852
TI  - Mitochondria coordinate sites of axon branching through localized intra-axonal
      protein synthesis.
AB  - The branching of axons is a fundamental aspect of nervous system development and
      neuroplasticity. We report that branching of sensory axons in the presence of
      nerve growth factor (NGF) occurs at sites populated by stalled mitochondria.
      Translational machinery targets to presumptive branching sites, followed by
      recruitment of mitochondria to these sites. The mitochondria promote branching
      through ATP generation and the determination of localized hot spots of active
      axonal mRNA translation, which contribute to actin-dependent aspects of
      branching. In contrast, mitochondria do not have a role in the regulation of the
      microtubule cytoskeleton during NGF-induced branching. Collectively, these
      observations indicate that sensory axons exhibit multiple potential sites of
      translation, defined by presence of translational machinery, but active
      translation occurs following the stalling and respiration of mitochondria at
      these potential sites of translation. This study reveals a local role for axonal
      mitochondria in the regulation of the actin cytoskeleton and axonal mRNA
      translation underlying branching. 

PMID- 24332853
TI  - PRMT4 blocks myeloid differentiation by assembling a methyl-RUNX1-dependent
      repressor complex.
AB  - Defining the role of epigenetic regulators in hematopoiesis has become critically
      important, because recurrent mutations or aberrant expression of these genes has
      been identified in both myeloid and lymphoid hematological malignancies. We found
      that PRMT4, a type I arginine methyltransferase whose function in normal and
      malignant hematopoiesis is unknown, is overexpressed in acute myelogenous
      leukemia patient samples. Overexpression of PRMT4 blocks the myeloid
      differentiation of human stem/progenitor cells (HSPCs), whereas its knockdown is
      sufficient to induce myeloid differentiation of HSPCs. We demonstrated that PRMT4
      represses the expression of miR-223 in HSPCs via the methylation of RUNX1, which
      triggers the assembly of a multiprotein repressor complex that includes DPF2. As
      part of the feedback loop, PRMT4 expression is repressed posttranscriptionally by
      miR-223. Depletion of PRMT4 results in differentiation of myeloid leukemia cells
      in vitro and their decreased proliferation in vivo. Thus, targeting PRMT4 holds
      potential as a novel therapy for acute myelogenous leukemia.

PMID- 24332854
TI  - MICU1 motifs define mitochondrial calcium uniporter binding and activity.
AB  - Resting mitochondrial matrix Ca(2+) is maintained through a mitochondrial calcium
      uptake 1 (MICU1)-established threshold inhibition of mitochondrial calcium
      uniporter (MCU) activity. It is not known how MICU1 interacts with MCU to
      establish this Ca(2+) threshold for mitochondrial Ca(2+) uptake and MCU activity.
      Here, we show that MICU1 localizes to the mitochondrial matrix side of the inner
      mitochondrial membrane and MICU1/MCU binding is determined by a MICU1 N-terminal
      polybasic domain and two interacting coiled-coil domains of MCU. Further
      investigation reveals that MICU1 forms homo-oligomers, and this oligomerization
      is independent of the polybasic region. However, the polybasic region confers
      MICU1 oligomeric binding to MCU and controls mitochondrial Ca(2+) current (IMCU).
      Moreover, MICU1 EF hands regulate MCU channel activity, but do not determine MCU
      binding. Loss of MICU1 promotes MCU activation leading to oxidative burden and a
      halt to cell migration. These studies establish a molecular mechanism for MICU1
      control of MCU-mediated mitochondrial Ca(2+) accumulation, and dysregulation of
      this mechanism probably enhances vascular dysfunction.

PMID- 24332855
TI  - Genome-wide RNAi screen identifies SEC61A and VCP as conserved regulators of
      Sindbis virus entry.
AB  - Alphaviruses are a large class of insect-borne human pathogens and little is
      known about the host-factor requirements for infection. To identify such factors,
      we performed a genome-wide RNAi screen using model Drosophila cells and validated
      94 genes that impacted infection of Sindbis virus (SINV), the prototypical
      alphavirus. We identified a conserved role for SEC61A and valosin-containing
      protein (VCP) in facilitating SINV entry in insects and mammals. SEC61A and VCP
      selectively regulate trafficking of the entry receptor NRAMP2, and loss or
      pharmacological inhibition of these proteins leads to altered NRAMP2 trafficking
      to lysosomal compartments and proteolytic digestion within lysosomes. NRAMP2 is
      the major iron transporter in cells, and loss of NRAMP2 attenuates intracellular
      iron transport. Thus, this study reveals genes and pathways involved in both
      infection and iron homeostasis that may serve as targets for antiviral
      therapeutics or for iron-imbalance disorders. 

PMID- 24332856
TI  - An optimized microRNA backbone for effective single-copy RNAi.
AB  - Short hairpin RNA (shRNA) technology enables stable and regulated gene
      repression. For establishing experimentally versatile RNAi tools and minimizing
      toxicities, synthetic shRNAs can be embedded into endogenous microRNA contexts.
      However, due to our incomplete understanding of microRNA biogenesis, such
      "shRNAmirs" often fail to trigger potent knockdown, especially when expressed
      from a single genomic copy. Following recent advances in design of synthetic
      shRNAmir stems, here we take a systematic approach to optimize the experimental
      miR-30 backbone. Among several favorable features, we identify a conserved
      element 3' of the basal stem as critically required for optimal shRNAmir
      processing and implement it in an optimized backbone termed "miR-E", which
      strongly increases mature shRNA levels and knockdown efficacy. Existing miR-30
      reagents can be easily converted to miR-E, and its combination with up-to-date
      design rules establishes a validated and accessible platform for generating
      effective single-copy shRNA libraries that will facilitate the functional
      annotation of the genome. 

PMID- 24332858
TI  - The synthesis of novel taxoids for oral administration.
AB  - A group of novel taxoids, with modifications at C-7, C-10, C-3' and C-14
      positions of paclitaxel, was synthesized in order to improve their biological
      profile by decreasing their affinity with P-glycoprotein (P-gp) and increasing
      cellular permeability. Most of the new taxoids demonstrated the similar potent
      cytotoxic activities in MCF-7 human tumor cell line as paclitaxel in vitro. In
      the permeability assay with monolayers of Caco-2 cells, most of the compounds
      demonstrated an increased trans-cellular transport in A-to-B direction in
      comparison with paclitaxel. Among them the compounds T-13, T-15 and T-26 showed
      the highest permeability, and with efflux ratios better than that of ortataxel.
      The interaction of the compounds T-13 and T-26 with P-gp was evaluated using
      Madin-Darby canine kidney (MDCK)-multidrug resistance-1(MDR1) and MDCK-wild-type
      (WT). The results indicated that T-13 and T-26 were poor substrates for P-gp and
      possessed inhibiting effects of P-gp mediated efflux. It was thus clear that
      simultaneous modifications at the C-7, C-10 and C-3' positions of paclitaxel
      significantly impaired its interactions with P-gp and interfered with P-gp
      mediated efflux. 

PMID- 24332857
TI  - Switch enhancers interpret TGF-beta and Hippo signaling to control cell fate in
      human embryonic stem cells.
AB  - A small toolkit of morphogens is used repeatedly to direct development, raising
      the question of how context dictates interpretation of the same cue. One example
      is the transforming growth factor beta (TGF-beta) pathway that in human embryonic
      stem cells fulfills two opposite functions: pluripotency maintenance and
      mesendoderm (ME) specification. Using proteomics coupled to analysis of genome
      occupancy, we uncover a regulatory complex composed of transcriptional effectors
      of the Hippo pathway (TAZ/YAP/TEAD), the TGF-beta pathway (SMAD2/3), and the
      pluripotency regulator OCT4 (TSO). TSO collaborates with NuRD repressor complexes
      to buffer pluripotency gene expression while suppressing ME genes. Importantly,
      the SMAD DNA binding partner FOXH1, a major specifier of ME, is found near TSO
      elements, and upon fate specification we show that TSO is disrupted with
      subsequent SMAD-FOXH1 induction of ME. These studies define switch-enhancer
      elements and provide a framework to understand how cellular context dictates
      interpretation of the same morphogen signal in development.

PMID- 24332859
TI  - Exploration of artistry in nursing teaching activities.
AB  - BACKGROUND: By promoting hope and providing care to patients, nurses serve as
      both artists and professionals in clinical contexts. However, current nursing
      education mainly emphasises the teaching of medical knowledge and skills. AIM:
      The aim of this study is to explore the perspectives of year one nursing
      undergraduates on the definitions of artistry and the relationship of artistry
      with the sciences and nursing care. DESIGN: A qualitative approach with content
      analysis was adopted in this study. METHODS: Seventeen students from a nursing
      problem-based learning (PBL) class participated in three artistic activities,
      namely composing songs, writing poems, and drawing, and in two rounds of
      interviews. Content analysis and peer checking was implemented to ensure that the
      generated results were trustworthy. RESULTS: According to the participants, it is
      probable that the artistic activities encouraged them to relate the arts to their
      daily lives. Some participants stated that they would like to show their
      consideration for patients through the arts. CONCLUSIONS: Although there was no
      consensus among the participants on the relation between artistry and the
      sciences/nursing, most of the students gained a better understanding of artistry
      and some were able to link nursing care with artistry. Nursing educators are
      encouraged to think beyond the boundaries of traditional teaching approaches and
      nurture their students with the artistry of clinical practice.

PMID- 24332860
TI  - Follow-up study in local allergic rhinitis shows a consistent entity not evolving
      to systemic allergic rhinitis.
AB  - BACKGROUND: Local allergic rhinitis (LAR) is a common disease that affects 25.7%
      of the rhinitis population and more than 47% of patients previously diagnosed
      with nonallergic rhinitis. Whether LAR is the first step in the natural history
      of allergic rhinitis (AR) with systemic atopy or a consistent entity is unknown.
      OBJECTIVE: The aim was to evaluate the natural history of a population with LAR
      of recent onset and the development of AR and asthma. METHODS: A prospective 10
      year follow-up study with initial cohorts of 194 patients with LAR of recent
      onset and 130 healthy controls is being undertaken. A clinical-demographic
      questionnaire, spirometry, skin prick test, and specific IgE to aeroallergens
      were done yearly. Nasal allergen provocation tests with Dermatophagoides
      pteronyssinus, Alternaria alternata, Olea europea, and a mix of grass pollen were
      performed at baseline and after 5 years. RESULTS: At disease onset, most of the
      patients with LAR had moderate-to-severe persistent-perennial rhinitis;
      conjunctivitis and asthma were the main comorbidities (51.1% and 18.8%,
      respectively), and D pteronyssinus was the most relevant aeroallergen (51.1%).
      After 5 years of follow-up, a worsening of rhinitis was detected in 26.2%, with
      an increase in symptom persistence and severity, and new associations with
      conjunctivitis and asthma. Atopy was detected by skin prick test and/or serum
      specific-IgE in patients with LAR (6.81%) and in controls (4.5%). CONCLUSIONS:
      This study shows a similar rate of development of systemic atopy in LAR and
      controls, which suggests that LAR is an entity well differentiated from AR. To
      determine the natural course of LAR more precisely, this study is in progress to
      complete 10 years of follow-up.

PMID- 24332861
TI  - Basal platelet-activating factor acetylhydrolase: prognostic marker of severe
      Hymenoptera venom anaphylaxis.

PMID- 24332862
TI  - Case fatality and population mortality associated with anaphylaxis in the United
      States.
AB  - BACKGROUND: Anaphylaxis is a serious allergic reaction that can cause death;
      however, the actual risk of death is unclear. OBJECTIVE: We sought to estimate
      the case fatality rate among hospitalizations or emergency department (ED)
      presentations for anaphylaxis and the mortality rate associated with anaphylaxis
      for the general population. METHODS: This was a population-based epidemiologic
      study using 3 national databases: the Nationwide Inpatient Sample (NIS; 1999
      2009), the Nationwide Emergency Department Sample (NEDS; 2006-2009), and Multiple
      Cause of Death Data (MCDD; 1999-2009). Sources for these databases are hospital
      and ED discharge records and death certificates, respectively. RESULTS: Case
      fatality rates were between 0.25% and 0.33% among hospitalizations or ED
      presentations with anaphylaxis as the principal diagnosis (NIS+NEDS, 2006-2009).
      These rates represent 63 to 99 deaths per year in the United States,
      approximately 77% of which occurred in hospitalized patients. The rate of
      anaphylaxis-related hospitalizations increased from 21.0 to 25.1 per million
      population between 1999 and 2009 (annual percentage change, 2.23%; 95% CI, 1.52%
      to 2.94%), contrasting with a decreasing case fatality rate among
      hospitalizations (annual percentage change, -2.35%; 95% CI, -4.98% to 0.34%).
      Overall mortality rates ranged from 0.63 to 0.76 per million population (186-225
      deaths per year, MCDD) and appeared stable in the last decade (annual percentage
      change, -0.31%; 95% CI, -1.54% to 0.93%). CONCLUSION: From 2006 to 2009, the
      overwhelming majority of hospitalizations or ED presentations for anaphylaxis did
      not result in death, with an average case fatality rate of 0.3%. Anaphylaxis
      related hospitalizations increased steadily in the last decade (1999-2009), but
      this increase was offset by the decreasing case fatality rate among those
      hospitalized; both inpatient and overall mortality rates associated with
      anaphylaxis appeared stable and were well under 1 per million population.
      Although anaphylactic reactions are potentially life-threatening, the probability
      of dying is actually very low. With the prevalence of anaphylaxis on the
      increase, practitioners need to stay vigilant and follow the treatment guidelines
      to further reduce anaphylaxis-related deaths.

PMID- 24332864
TI  - Cold ambient temperature in utero and birth outcomes in Uppsala, Sweden, 1915
      1929.
AB  - PURPOSE: Although the literature reports adverse birth outcomes following ambient
      heat, less work focuses on cold. We, moreover, know of no studies of cold that
      examine stillbirth. We tested the relation between cold ambient temperature
      during pregnancy in Sweden and four outcomes: stillbirth, preterm, birth weight
      for gestational age, and birth length. We examined births from 1915 to 1929 in
      Uppsala, Sweden, which-unlike most societies today-experienced substandard indoor
      heating and fewer amenities to provide shelter from cold. METHODS: We retrieved
      data on almost 14,000 deliveries from the Uppsala Birth Cohort Study. We linked a
      validated, daily ambient temperature series to all pregnancies and applied Cox
      proportional hazards (stillbirth and preterm) and linear regression models (birth
      weight and length). We tested for nonlinearity using quadratic splines. RESULTS:
      The risk of stillbirth rose as ambient temperature during pregnancy fell (hazard
      ratio for a 1 degrees C decrease in temperature, 1.08; 95% confidence interval,
      1.00 to 1.17). Cold extremes adversely affected preterm and birth length, whereas
      warm extremes increased preterm risk. We observed no relation between cold and
      birth weight for gestational age. CONCLUSION: In historical Sweden, cold
      temperatures during pregnancy increased stillbirth and preterm risk and reduced
      birth length among live births.

PMID- 24332863
TI  - Local geographic variation in chronic liver disease and hepatocellular carcinoma:
      contributions of socioeconomic deprivation, alcohol retail outlets, and
      lifestyle.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) incidence rates continue to increase in
      the United States. Geographic variation in rates suggests a potential
      contribution of area-based factors, such as neighborhood socioeconomic
      deprivation, retail alcohol availability, and access to health care. METHODS:
      Using the National Institutes of Health-American Association of Retired Persons
      Diet and Health Study, we prospectively examined area socioeconomic variations in
      HCC incidence (n = 434 cases) and chronic liver disease (CLD) mortality (n = 805
      deaths) and assessed contribution of alcohol outlet density, health care
      infrastructure, diabetes, obesity, and health behaviors. Hazard ratios (HRs) and
      95% confidence intervals (CIs) were estimated from hierarchical Cox regression
      models. RESULTS: Area socioeconomic deprivation was associated with increased
      risk of HCC incidence and CLD mortality (HR, 1.48; 95% CI, 1.03-2.14 and HR,
      2.36; 95% CI, 1.79-3.11, respectively) after accounting for age, sex, and race.
      After additionally accounting for educational attainment and health risk factors,
      associations for HCC incidence were no longer significant; associations for CLD
      mortality remained significant (HR, 1.78; 95% CI, 1.34-2.36). Socioeconomic
      status differences in alcohol outlet density and health behaviors explained the
      largest proportion of socioeconomic status-CLD mortality association, 10% and
      29%, respectively. No associations with health care infrastructure were observed.
      CONCLUSIONS: Our results suggest a greater effect of area-based factors for CLD
      than HCC. Personal risk factors accounted for the largest proportion of variance
      for HCC but not for CLD mortality.

PMID- 24332865
TI  - [Brachytherapy training: a survey of French radiation oncology residents].
AB  - PURPOSE: The goal of this study was to evaluate the interest of the members of
      the French society of young radiation oncologists (SFjRO) for brachytherapy as
      well as their theoretical and practical level in this radiation technique.
      MATERIALS AND METHODS: An anonymous survey was conducted regarding practical and
      theoretical teaching of brachytherapy before the French national courses on
      brachytherapy. RESULTS: Among the 106 residents attending this teaching course,
      99 (93%) answered the survey. Most of them were interested in brachytherapy but
      82% considered they had not received sufficient teaching. Relevant indications of
      brachytherapy were known by 76% of the residents for gynaecological malignancies
      and 70% for prostate. Seventy-one percent of the residents have seen at least one
      gynecological brachytherapy but only 12% knew how to deal with this technique.
      Fifty-six percent have seen vaginal high dose rate brachytherapy and 21% had
      acquired the technique. For prostate brachytherapy, 65% had seen and done an
      implant and only 4% had acquired the technique. Fifty percent have performed at
      least one brachytherapy treatment during their residency. Residents expressed a
      strong wish for more courses about dosimetry (82%), technique (75%) and treatment
      planning (90%). CONCLUSION: Our study shows the interest of French residents for
      brachytherapy but suggests that practical teaching courses and an evaluation of
      the existing theoretical courses are warranted.

PMID- 24332869
TI  - Crohn's disease outcome in patients under azathioprine: a tertiary referral
      center experience.
AB  - BACKGROUND AND AIMS: Azathioprine is of major importance in the treatment of
      Crohn's disease; its efficacy has been showed in several works, but real-life
      data regarding its use is scarce. Our aim was to address the outcome of patients
      with Crohn's disease under azathioprine in the real-life setting. METHODS:
      Crohn's disease patients followed at an Inflammatory Bowel Disease Outpatient
      Clinic under azathioprine were consecutively enrolled, being allocated in one of
      four groups. Two groups included patients on treatment with this drug, regarding
      its two major indications - prevention of post-operative recurrence and steroid
      dependent disease; a third group included patients who needed infliximab in
      addition to azathioprine and a fourth group comprised patients who did not
      tolerate azathioprine. RESULTS: A total of 221 patients were enrolled, 180 on
      azathioprine due to steroid-dependency (64 needing additional treatment with
      infliximab) and 41 for prevention of post-operative recurrence. Steroid-free
      remission was obtained in 48%. Immunosuppression decreased the number of
      hospitalized patients (64% vs 36%; p<0.001), but not the surgery rates per person
      per year. Azathioprine as a post-operative drug was effective in decreasing
      hospitalizations. The addition of infliximab decreased the number of patients
      hospitalized (p=0.009) and hospitalization rates per person per year (p<0.001),
      but had no effect in the surgery rates per person per year. Sixty patients (23%)
      experienced adverse effects with AZA, 39 requiring discontinuation of the drug.
      CONCLUSIONS: In this real-life study, azathioprine had a long-term steroid
      sparing effect and reduced hospitalizations. Combination with infliximab reduced
      hospitalizations but did not decrease the surgery rate.

PMID- 24332870
TI  - Influence of combinations of drugs that act on the CYP2D6 metabolic pathway in
      the treatment of major depressive disorder: a population-based study.
AB  - OBJECTIVE: To describe the frequency of drug combinations (substrate-substrate or
      substrate-inhibitor) with the potential to interfere with the CYP2D6 metabolic
      pathway in patients receiving antidepressant medication for major depressive
      disorder. METHODS: We carried out an observational study using outpatient medical
      records. We included adult subjects who initiated antidepressant medication
      during 2008-2010. Patients were assigned to three study groups: no combination,
      substrate-substrate, and substrate-inhibitor. Follow-up period was 12 months.
      MAIN MEASURES: demographics, comorbidity and medication persistence. Statistical
      analysis included a logistic regression model, P<0.05. RESULTS: Five thousand six
      hundred and thirty patients were recruited (61.9 years, 76.9% female), 24.4% (CI:
      23.8 - 26.0%) received some kind of drug combination (substrate-substrate: 15.4%,
      substrate-inhibitor: 9.0%). Variables significantly associated with drugs
      combinations that may act on the CYP2D6 metabolic pathway were: dementia
      (OR=4.2), neuropathy (OR=4.2) and stroke (OR=1.9), P<0.001. Medication
      persistence at 12 months was longer in patients with no combination (55.3%) than
      in patients receiving substrate-substrate (50.5%) or substrate-inhibitor (45.0%)
      combinations, P<0.001. CONCLUSIONS: Twenty-five percent of major depressive
      disorder patients received a combination of drugs with the potential to interfere
      with CYP2D6 metabolic pathway. These combinations increased with comorbidity and
      resulted in shorter medication persistence of antidepressant treatment.

PMID- 24332871
TI  - Central nervous system involvement in hemophagocytic lymphohistiocytosis: a
      single-center experience.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis is a rare multisystem disorder
      characterized by proliferation and diffuse infiltration multiple organs with
      histiocytes, including the central nervous system. PATIENTS AND METHODS: Thirty
      children diagnosed with hemophagocytic lymphohistiocytosis between 1997 and 2010
      were reviewed and analyzed. Central nervous system disease involvement was
      defined as the presence of neurological symptoms and signs or elevated values of
      cerebrospinal fluid cells and/or proteins. RESULTS: Among the 30 patients, 17
      (56%) had central nervous system involvement. Fourteen patients (46%) presented
      with neurological symptoms including seizures, irritability, bulging fontanelle,
      cranial nerve palsy, or disturbance of consciousness, whereas the remaining three
      patients developed central nervous system symptoms during the course of the
      disease. Seventeen patients (56%) had cerebrospinal fluid abnormalities.
      Neuroradiological studies were performed in nine patients. The most common
      findings were edema, atrophy, subcortical necrosis, and high signal intensity on
      T2-weighted magnetic resonance imaging. All patients were treated according to
      the Hemophagocytic Lymphohistiocytosis-94 and Hemophagocytic Lymphohistiocytosis
      2004 protocols. Patients with central nervous system involvement had greater
      mortality. In prediction of the outcome, the cutoff value for cerebrospinal fluid
      protein was 470 mg/L. The most common neurological sequela was psychomotor delay.
      CONCLUSION: Central nervous system involvement in hemophagocytic
      lymphohistiocytosis is common and is associated with poor outcome.

PMID- 24332872
TI  - Influence of number of deliveries and total breast-feeding time on bone mineral
      density in premenopausal and young postmenopausal women.
AB  - OBJECTIVES: Pregnancy and lactation have been associated with decline in bone
      mineral density (BMD). It is not clear if there is a full recovery of BMD to
      baseline. This study sought to determine if pregnancy or breast-feeding or both
      have a cumulative effect on BMD in premenopausal and early postmenopausal women.
      STUDY DESIGN: We performed single-center cohort analysis. Five hundred women aged
      35-55 years underwent routine BMD screening from February to July 2011 at a
      tertiary medical center. Patients were questioned about number of total full-term
      deliveries and duration of breast-feeding and completed a background
      questionnaire on menarche and menopause, smoking, dairy product consumption, and
      weekly physical exercise. Weight and height were measured. Dual-energy X-ray
      absorptiometry was used to measure spinal, dual femoral neck, and total hip BMD.
      MAIN OUTCOME MEASURES: Associations between background characteristics and BMD
      values were analyzed. RESULTS: Sixty percent of the women were premenopausal.
      Mean number of deliveries was 2.5 and mean duration of breast-feeding was 9.12
      months. On univariate analysis, BMD values were negatively correlated with
      patient age (p=0.006) and number of births (p=0.013), and positively correlated
      with body mass index (p<0.001). On multiple (adjusted) logistic regression
      analysis, prolonged breast-feeding duration, but not number of deliveries, was
      significantly correlated to a low BMD (p=0.008). An effect was noted only in
      postmenopausal women. The spine was the most common site of BMD decrease.
      CONCLUSIONS: Prolonged breast-feeding may have a deleterious long-term effect on
      BMD and may contribute to increased risk of osteoporosis later in life.

PMID- 24332873
TI  - Editorial fairness: speed, accuracy and awareness benefit authors.

PMID- 24332874
TI  - What is the future of conservation?
AB  - In recent years, some conservation biologists and conservation organizations have
      sought to refocus the field of conservation biology by de-emphasizing the goal of
      protecting nature for its own sake in favor of protecting the environment for its
      benefits to humans. This 'new conservation science' (NCS) has inspired debate
      among academics and conservationists and motivated fundamental changes in the
      world's largest conservation groups. Despite claims that NCS approaches are
      supported by biological and social science, NCS has limited support from either.
      Rather, the shift in motivations and goals associated with NCS appear to arise
      largely from a belief system holding that the needs and wants of humans should be
      prioritized over any intrinsic or inherent rights and values of nature. 

PMID- 24332875
TI  - [The other side of Sweet's syndrome: neutrophilic dermatosis of the back of the
      hands associated with a renal tumour].

PMID- 24332877
TI  - Lingual nerve injury following use of a supraglottic airway device.
AB  - We present the case of a 64-year-old woman who lost sensation on the left side of
      her tongue after an orthopaedic procedure under general anaesthetic. It provides
      evidence that anaesthetic airway devices can injure the lingual nerve. 

PMID- 24332878
TI  - Reduce, reuse and recycle: a green solution to Canada's medical isotope shortage.
AB  - Due to the unforeseen maintenance issues at the National Research Universal (NRU)
      reactor at Chalk River and coincidental shutdowns of other international
      reactors, a global shortage of medical isotopes (in particular technetium-99m, Tc
      99m) occurred in 2009. The operation of these research reactors is expensive,
      their age creates concerns about their continued maintenance and the process
      results in a large amount of long-lived nuclear waste, whose storage cost has
      been subsidized by governments. While the NRU has since revived its operations,
      it is scheduled to cease isotope production in 2016. The Canadian government
      created the Non-reactor based medical Isotope Supply Program (NISP) to promote
      research into alternative methods for producing medical isotopes. The NRC was a
      member of a collaboration looking into the use of electron linear accelerators
      (LINAC) to produce molybdenum-99 (Mo-99), the parent isotope of Tc-99m. This
      paper outlines NRC's involvement in every step of this process, from the
      production, chemical processing, recycling and preliminary animal studies to
      demonstrate the equivalence of LINAC Tc-99m with the existing supply. This
      process stems from reusing an old idea, reduces the nuclear waste to virtually
      zero and recycles material to create a green solution to Canada's medical isotope
      shortage. 

PMID- 24332879
TI  - Improvements of low-level radioxenon detection sensitivity by a state-of-the art
      coincidence setup.
AB  - The ability to quantify isotopic ratios of 135, 133 m, 133 and 131 m radioxenon
      is essential for the verification of the Comprehensive Nuclear-Test Ban Treaty
      (CTBT). In order to improve detection limits, CEA has developed a new on-site
      setup using photon/electron coincidence (Le Petit et al., 2013. J. Radioanal.
      Nucl. Chem., DOI : 10.1007/s 10697-013-2525-8.). Alternatively, the electron
      detection cell equipped with large silicon chips (PIPS) can be used with HPGe
      detector for laboratory analysis purpose. This setup allows the measurement of
      beta/gamma coincidences for the detection of (133)Xe and (135)Xe; and K-shell
      Conversion Electrons (K-CE)/X-ray coincidences for the detection of (131m)Xe,
      (133m)Xe and (133)Xe as well. Good energy resolution of 11 keV at 130 keV and low
      energy threshold of 29 keV for the electron detection were obtained. This
      provides direct discrimination between K-CE from (133)Xe, (133m)Xe and (131m)Xe.
      Estimation of Minimum Detectable Activity (MDA) for (131m)Xe is in the order of
      1mBq over a 4 day measurement. An analysis of an environmental radioxenon sample
      using this method is shown.

PMID- 24332880
TI  - (9)Be(d,n)(10)B-based neutron sources for BNCT.
AB  - In the frame of accelerator-based BNCT, the (9)Be(d,n)(10)B reaction was
      investigated as a possible source of epithermal neutrons. In order to determine
      the configuration in terms of bombarding energy, target thickness and Beam
      Shaping Assembly (BSA) design that results in the best possible beam quality, a
      systematic optimization study was carried out. From this study, the optimal
      configuration resulted in tumor doses >=40Gy-Eq, with a maximum value of 51Gy-Eq
      at a depth of about 2.7cm, in a 60min treatment. The optimal configuration was
      considered for the treatment planning assessment of a real Glioblastoma
      Multiforme case. From this, the resulted dose performances were comparable to
      those obtained with an optimized (7)Li(p,n)-based neutron source, under identical
      conditions and subjected to the same clinical protocol. 

PMID- 24332881
TI  - Slovenian-Romanian bilateral intercomparison on tritium samples.
AB  - A Slovenian laboratory from the Jozef Stefan Institute (JSI) and a Romanian
      laboratory from the National Research and Development Institute for Cryogenics
      and Isotopic Technologies (ICIT) performed bilateral intercomparisons of tritium
      determination in environmental samples. On the basis of the results, the
      measurement and analysis methods were compared. Comparability and traceability
      were confirmed with the results from international radioactivity proficiency test
      exercises organized by IAEA and NPL where both laboratories participated. New
      knowledge gained leads to harmonized, precise and traceable results of low level
      tritium environmental samples measurements. 

PMID- 24332882
TI  - Immunogenicity and protection conferred by Mycobacterium habana in a murine model
      of pulmonary tuberculosis.
AB  - Mycobacterium habana was isolated in Cuba in 1971. Later, was demonstrated its
      protection capacity in mycobacterial infection. Here we determined the level of
      virulence, immunogenicity and the efficacy of three different M. habana strains
      as attenuated live vaccines. Intratracheal infection of BALB/c mice with high
      dose M. habana TMC 5135 or IPK-337 strains permitted 100% survival and limited
      tissue damage. Mice infected with M. habana IPK-220 showed lower attenuation, so
      it was discarded for the vaccination experiments. Strains IPK-337 and TMC 5135
      were used as subcutaneous vaccine and compared with BCG. Nude mice vaccinated
      with strain 5135 showed longer but non-significant survival than BCG vaccinated
      animals. Cell suspensions from M. habana vaccinated mice produced higher IFNgamma
      after stimulation with mycobacterial antigens than BCG recipients. After four
      months of challenge with Mycobacterium tuberculosis strain H37Rv, mice vaccinated
      with BCG substrain Phipps or strain TMC 5135 showed total survival, while 60%
      survival was exhibited by animals vaccinated with M. habana IPK-337. Both M.
      habana strains do not prevent the infection with M. tuberculosis but avoided the
      progression of the experimental disease; strain TMC 5135 showed similar level of
      protection than BCG. 

PMID- 24332883
TI  - Trend of human rabies prophylaxis in developing countries: toward optimal rabies
      immunization.

PMID- 24332884
TI  - Remission of food allergy by the Janus kinase inhibitor ruxolitinib in mice.
AB  - To clarify the role of Janus kinase (JAK) in and the efficacy of JAK inhibitors
      on food allergy, we investigated the effect of the clinically available JAK
      inhibitor ruxolitinib on mouse food allergy and the functions of cultured mast
      cells in vitro. Anaphylactic symptoms including diarrhea and decreases in body
      temperature pursuant to oral ovalbumin (OVA) challenges in food allergy mice were
      attenuated by the daily oral administration of ruxolitinib. This drug inhibited
      increases in mouse mast cell protease-1 concentrations in the serum and mast cell
      numbers in the intestines of these mice as well as degranulation, IL-13
      production, and the spontaneous and IL-9-dependent survival of mouse bone marrow
      derived mast cells in spite of the absence of an effect of ruxolitinib on passive
      systemic anaphylaxis. Anti-OVA IgG2a, IgE, and IgG1 serum levels and the release
      of IFN-gamma, IL-4, IL-9, and IL-10 from the OVA-restimulated splenocytes of food
      allergy mice were also decreased by the treatment. Moreover, ruxolitinib
      administration to mice that had already exhibited anaphylactic responses to
      previous challenges reduced anaphylactic responses to further oral OVA
      challenges, which suggested that ruxolitinib has a therapeutic potential on food
      allergy. Our results showed that ruxolitinib remitted food allergy in mice mainly
      through immunosuppression and the prevention of mast cell hyperplasia, and
      partially through the inhibition of mast cell activation. We consider JAK
      inhibition to be a promising strategy for the prevention of food allergy, and
      ruxolitinib along with its derivatives inhibiting JAK as good candidates for
      therapeutic drugs to treat food allergy. 

PMID- 24332885
TI  - Authors' reply to "Analysis of the diastolic function by myocardial perfusion
      gated SPECT after coronary revascularization in acute myocardial infarction".

PMID- 24332886
TI  - Comment on "Analysis of the diastolic function by myocardial perfusion gated
      SPECT after coronary revascularization in acute myocardial infarction".

PMID- 24332887
TI  - Visually weighted reconstruction of compressive sensing MRI.
AB  - Compressive sensing (CS) enables the reconstruction of a magnetic resonance (MR)
      image from undersampled data in k-space with relatively low-quality distortion
      when compared to the original image. In addition, CS allows the scan time to be
      significantly reduced. Along with a reduction in the computational overhead, we
      investigate an effective way to improve visual quality through the use of a
      weighted optimization algorithm for reconstruction after variable density random
      undersampling in the phase encoding direction over k-space. In contrast to
      conventional magnetic resonance imaging (MRI) reconstruction methods, the visual
      weight, in particular, the region of interest (ROI), is investigated here for
      quality improvement. In addition, we employ a wavelet transform to analyze the
      reconstructed image in the space domain and fully utilize data sparsity over the
      spatial and frequency domains. The visual weight is constructed by reflecting the
      perceptual characteristics of the human visual system (HVS), and then applied to
      l1 norm minimization, which gives priority to each coefficient during the
      reconstruction process. Using objective quality assessment metrics, it was found
      that an image reconstructed using the visual weight has higher local and global
      quality than those processed by conventional methods. 

PMID- 24332888
TI  - Lectin pathway of complement activation in a Polish woman with MASP-2 deficiency.

PMID- 24332889
TI  - Altered receptor binding densities in experimental antiphospholipid syndrome
      despite only moderately enhanced autoantibody levels and absence of behavioral
      features.
AB  - Experimental antiphospholipid syndrome (eAPS) in Balb/c mice causes
      neuropsychiatric abnormalities including hyperactivity, increased explorative
      behavior and cognitive deficits. Recently, we have demonstrated that these
      behavioral changes were linked to an upregulation of serotonergic 5-HT1A receptor
      binding densities in cortical and hippocampal regions while excitatory and
      inhibitory neurotransmitter receptors remain largely unchanged. To examine
      whether the observed behavioral features depend on a critical antibody
      concentration, mice with only moderately enhanced antiphospholipid antibodies
      (aPL), about 50-80% of high levels, were analyzed and compared to controls. The
      staircase test was used to test animals for hyperactivity and explorative
      behavior. The brains were analyzed for tissue integrity and inflammation. Ligand
      binding densities of NMDA, AMPA, GABAA, 5-HT1A, M1 and M2 muscarinic
      acetylcholine receptors, respectively, were analyzed by in vitro receptor
      autoradiography and compared to brains of mice from our previous study with high
      levels of aPL. Mice with only moderately enhanced aPL did not develop significant
      behavioral changes. Brain parenchyma remained intact and neither inflammation nor
      glial activation was detectable. However, there was a significant decrease of
      NMDA receptor binding densities in the motor cortex as well as an increase in M1
      binding densities in cortical and hippocampal regions, whereas the other
      receptors analyzed were not altered. Lack of neuropsychiatric symptoms may be due
      to modulations of receptors resulting in normal behavior. In conclusion, our
      results support the hypothesis that high levels of aPL are required for the
      manifestation of neuropsychiatric involvement while at lower antibody levels
      compensatory mechanisms may preserve normal behavior. 

PMID- 24332890
TI  - Functional effects of chronic paroxetine versus placebo on the fear, stress and
      anxiety brain circuit in Social Anxiety Disorder: initial validation of an
      imaging protocol for drug discovery.
AB  - Recent studies suggest that pharmacologic effects of anxiolytic agents can be
      mapped as functional changes in the fear, stress and anxiety brain circuit. In
      this work we investigated the effects of a standard treatment, paroxetine
      (20mg/day), in subjects with Social Anxiety Disorder (SAD) versus placebo using
      different fMRI paradigms. The fMRI sessions, performed before and after the
      treatment, consisted of a public exposition of recorded performance task (PERPT),
      an emotional face processing task (EFPT) and a 6-min resting state followed by an
      off-scanner public speaking test. Paroxetine significantly improved the clinical
      conditions of SAD patients (n=17) vs. placebo (n=16) as measured with Clinical
      Global Inventory - Improvement (CGI-I) while no change was seen when using
      Liebowitz Social Anxiety Scale, as expected given the small size of the study
      population. Paroxetine reduced the activation of insula, thalamus and
      subgenual/anterior cingulate cortex (ACC) in PERPT. Resting-state fMRI assessment
      using Independent Component Analysis indicated that paroxetine reduced functional
      connectivity in insula, thalamus and ACC when compared with placebo. Both
      paradigms showed significant correlation with CGI-I in rostral prefrontal cortex.
      Conversely, paroxetine compared to placebo produced activation of right amygdala
      and bilateral insula and no effects in ACC when tested with EFPT. No treatment
      effects on distress scores were observed in the off-scanner Public Speaking Test.
      Overall this study supports the use of fMRI as sensitive approach to explore the
      neurobiological substrate of the effects of pharmacologic treatments and, in
      particular, of resting state fMRI given its simplicity and task independence. 

PMID- 24332891
TI  - Evaluating negative-symptom-like behavioural changes in developmental models of
      schizophrenia.
AB  - Many lines of evidence suggest that schizophrenia has a major developmental
      component and that environmental factors that disrupt key stages of development,
      such as maternal stress during pregnancy as a result of infection or
      malnutrition, can increase the risk of developing schizophrenia in later life.
      This review examines how non-clinical neurodevelopmental models pertinent to
      schizophrenia have been evaluated for their ability to reproduce behavioural
      deficits related to the negative symptoms of schizophrenia. The more frequently
      used are the prenatal application of the mitotoxic agent methylazoxymethanol,
      prenatal immune challenge and the neonatal ventral hippocampus lesion model. In
      general they have been extensively evaluated in models considered relevant to
      positive symptoms of schizophrenia. In contrast, very few studies have examined
      tests related to negative symptoms and, when they have, it has almost exclusively
      been a social interaction model. Other aspects related to negative symptoms such
      as anhedonia, affective flattening and avolition have almost never been studied.
      Further studies examining other components of negative symptomatology are needed
      to more clearly associate these deficits with a schizophrenia-like profile as
      social withdrawal is a hallmark of many disorders. Although there are no truly
      effective treatments for negative symptoms, better characterisation with a
      broader range of drugs used in schizophrenia will be necessary to better evaluate
      the utility of these models. In summary, developmental models of schizophrenia
      have been extensively studied as models of positive symptoms but, given the unmet
      need in the clinic, the same effort now needs to be made with regard to negative
      symptoms. 

PMID- 24332892
TI  - The effect of a skipped dose (placebo) of methylphenidate on the learning and
      retention of a motor skill in adolescents with Attention Deficit Hyperactivity
      Disorder.
AB  - Individuals with Attention Deficit Hyperactivity Disorder (ADHD) have
      difficulties in achieving optimal performance in many everyday and academic
      tasks, deficits attributed to impaired skill acquisition and procedural memory
      consolidation. We tested the effect of a skipped dose of methylphenidate (MPH) on
      learning a movement sequence and its subsequent consolidation into procedural
      memory in adolescents with ADHD. A crossover double-blind design with placebo was
      used. Sixteen male adolescents, 16-18 years-old, with ADHD and taking MPH
      formulations on a daily basis, were trained on performing a 5-element sequence of
      finger-to-thumb opposition movements. Participants took part in two study
      conditions, 2 months apart. In each condition a different movement sequence was
      trained and tested. Participants trained on the task either with active
      medication or placebo on the day of training, crossed-over between study
      conditions. Learning effects, speed and accuracy, were assessed within-session,
      during a 24-h memory consolidation phase. Retention was tested by 2 weeks post
      training. There were robust gains in performance both within-session and during
      the 24-h consolidation phase, in both conditions. However, the discontinuation of
      MPH on the day of training significantly reduced performance speed, with no loss
      of accuracy. By 2 weeks, post-training performance was comparable. Adolescents
      with ADHD who are treated daily but skip a dose of MPH show significant slowing
      of performance relative to their own performance on medication. However, on a
      background of daily treatment a skipped dose has no deleterious effect on memory
      consolidation and retention. 

PMID- 24332893
TI  - Integration of fluoridated implants in onlay autogenous bone grafts - an
      experimental study in the rabbit tibia.
AB  - INTRODUCTION: Bone augmentation before treatment with endosseous implants is a
      common procedure for rehabilitation of the edentulous jaw. Both machined and
      surface modified implants have been used in one-stage and two-stage surgery
      protocols with varying results and survival rates. The influence of surface
      modification on the integration of implants has been documented in both non
      grafted and grafted bone. The aim of this study was to compare the integration
      and stability of surface modified fluoridated vs. machined implants when placed
      simultaneously with an onlay bone graft. MATERIAL AND METHODS: Eight rabbits were
      used in this study. A disc shaped bone graft was harvested from each side of the
      sagittal suture of the calvarial bone and fixed bi-cortically to the proximal
      tibial metaphysis by means of a dental implant, 9 mm long and 3.5 mm in diameter
      with a smooth machined surface as control and a blasted, fluoridated surface as
      test. Test and control sides were randomised. After a healing time of 8 weeks,
      the rabbits were sacrificed and the implants were removed en block for light
      microscopic analysis. Bone to implant contact (BIC) was registered as well as the
      amount of bone filling a rectangle indicating a region of interest (ROI) in the
      grafted area. Resonance frequency analysis (RFA) was conducted both at the time
      of surgery and at the end of the study. RESULTS: Our results showed statistically
      significant differences in BIC within the grafted area and the total bone to
      implant contact between the test and control sides in favour of the surface
      modified implants. The bone area filling the threads within a region of interest
      showed no statistically significant difference between the test and control
      sides. RFA showed higher implant stability with significant differences at the
      time of sacrifice in favour of the fluoridated implants. CONCLUSION: Surface
      modified fluoridated implants showed a higher degree of osseointegration and
      stability in onlay bone grafts compared with control implants with machined
      surface texture.

PMID- 24332894
TI  - Design parameters and the material coupling are decisive for the micromotion
      magnitude at the stem-neck interface of bi-modular hip implants.
AB  - Several bi-modular hip prostheses exhibit an elevated number of fretting-related
      postoperative complications most probably caused by excessive micromotions at
      taper connections. This study investigated micromotions at the stem-neck
      interface of two different designs: one design (Metha, Aesculap AG) has
      demonstrated a substantial number of in vivo neck fractures for Ti-Ti couplings,
      but there are no documented fractures for Ti-CoCr couplings. Conversely, for a
      comparable design (H-Max M, Limacorporate) with a Ti-Ti coupling only one
      clinical failure has been reported. Prostheses were mechanically tested and the
      micromotions were recorded using a contactless measurement system. For Ti-Ti
      couplings, the Metha prosthesis showed a trend towards higher micromotions
      compared to the H-Max M (6.5 +/- 1.6 MUm vs. 3.6 +/- 1.5 MUm, p=0.08).
      Independent of the design, prostheses with Ti neck adapter caused significantly
      higher interface micromotions than those with CoCr ones (5.1 +/- 2.1 MUm vs. 0.8
      +/- 1.6 MUm, p=0.001). No differences in micromotions between the Metha
      prosthesis with CoCr neck and the H-Max M with Ti neck were observed (2.6 +/- 2.0
      MUm, p=0.25). The material coupling and the design are both crucial for the
      micromotions magnitude. The extent of micromotions seems to correspond to the
      number of clinically observed fractures and confirm the relationship between
      those and the occurrence of fretting corrosion.

PMID- 24332895
TI  - Loa loa-does it deserve to be neglected?
AB  - More than 10 million people in western and central Africa are estimated to be
      infected with Loa loa filarial nematodes. Like most other infectious diseases, L
      loa filariasis (loiasis) covers a wide range of symptoms. Severe complications
      have been reported; however, most observations are anecdotal, typically in
      travellers. The widespread use of filaricidal drugs within eradication programmes
      of Onchocerca volvulus and Wuchereria bancrofti led to the observation that
      concomitant L loa infection increases the risk of severe treatment-associated,
      life-threatening complications. Initiatives were therefore launched to map the
      risk of loiasis. Insight about the epidemiology of L loa has advanced notably;
      however, its effect on the individual as well as on the community level has not
      been well studied. In the absence of appropriate studies, L loa is commonly
      judged a harmless nematode, and loiasis as a separate entity does not belong to
      the list of neglected tropical diseases to be controlled or eradicated in
      worldwide campaigns. We advocate reorientation of research efforts towards a
      patient-centric view of loiasis and, as a first step, to establish the disease
      burden in disability-adjusted life-years of this chronic infection, and to answer
      the question of whether loiasis should be included in future control programmes. 

PMID- 24332896
TI  - Expanding spectrum of electroclinical findings in patients with karyotype 47,XYY.

PMID- 24332898
TI  - Successful treatment of ileocolic intussusception with air enema reduction in an
      adult patient.
AB  - Intussusception is a rare condition in adults, representing only 1% of all bowel
      obstructions. In adult cases, operative explorations are recommended to treat the
      bowel obstruction and to diagnose underlying diseases. The objective of the
      current case report was to describe the successful treatment of ileocolic
      intussusception with air enema reduction in an adult patient. A previously
      healthy 21-year-old woman had a 20-hour history of colicky abdominal pain and
      vomiting and was diagnosed as having idiopathic ileocolic intussusception by
      abdominal computed tomography. We treated the patient with air enema reduction
      under fluoroscopic guidance instead of an operative procedure. She received
      oxygen and intravenous midazolam to provide some degree of pain relief. Air was
      carefully pumped manually into the rectum, and the air pressure was monitored
      with a manometer. Because of air leakage from the rectum through the void to the
      outside the body, we continued to provide air to maintain the air pressure
      between 40 and 60 mm Hg. Three minutes after initiation of the air enema, when
      the patient experienced increasing abdominal pain and vomiting, the pressure was
      temporarily increased to greater than 100 mm Hg, and the air reached the terminal
      ileum. We considered the reduction successful and confirmed it with an abdominal
      ultrasound examination. We believe that air enema reduction is effective for
      treating idiopathic intussusception within 24 hours of symptom onset in young,
      previously healthy adult patients.

PMID- 24332897
TI  - Aortic coarctation associated with aortic valve stenosis and mitral regurgitation
      in an adult patient: a two-stage approach using a large-diameter stent graft.
AB  - We report a case of a staged surgical and endovascular management in a 62-year
      old woman with aortic coarctation associated with aortic valve stenosis and
      mitral regurgitation. The patient was admitted for severe aortic valve stenosis
      and mitral valve incompetence. During hospitalization and preoperative imaging, a
      previously undiagnosed aortic coarctation was discovered. The patient underwent a
      2-stage approach that combined a Bentall procedure and mitral valve replacement
      in the first stage, followed by correction of the aortic coarctation by
      percutaneous placement of an Advanta V12 large-diameter stent graft (Atrium,
      Mijdrecht, The Netherlands) which to our knowledge has not been used in an adult
      patient with this combination of additional cardiac comorbidities. A staged
      approach combining surgical treatment first and endovascular placement of an
      Advanta V12 stent graft in the second stage can be effective and safe in adult
      patients with coarctation of the aorta and additional cardiac comorbidities. 

PMID- 24332899
TI  - Case report: Pig attack with successful postexposure prophylaxis management.
AB  - The domesticated pig or boar is ubiquitous to agriculture around the world and is
      an important food product in most countries. The males that are able to grow
      tusks that can approach 5 in are the primary contributor to morbidity and
      mortality from boar attacks. Literature surrounding domesticated boar attacks is
      sparse. There are no published cases of domesticated boar attacks that describe
      successful bacterial postexposure prophylaxis. We present a case report of an
      attack on an adult female by a domesticated boar.

PMID- 24332900
TI  - The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital
      mortality and metabolic disturbances.
AB  - OBJECTIVE: To determine the ability of prehospital end-tidal carbon dioxide
      (ETCO2) to predict in-hospital mortality compared to conventional vital signs.
      METHODS: We conducted a retrospective cohort study among patients transported by
      emergency medical services during a 29-month period. Included patients had ETCO2
      recorded in addition to initial vital signs. The main outcome was death at any
      point during hospitalization. Secondary outcomes included laboratory results and
      admitting diagnosis. RESULTS: Of 1328 records reviewed, hospital discharge data,
      ETCO2, and all 6 prehospital vital signs were available in 1088 patients. Low
      ETCO2 levels were the strongest predictor of mortality in the overall group (area
      under the receiver operating characteristic curve (AUC of 0.76, 95% confidence
      interval [CI] 0.66-0.85), as well as subgroup analysis excluding prehospital
      cardiac arrest (AUC of 0.77, 95% CI 0.67-0.87). The sensitivity of abnormal ETCO2
      for predicting mortality was 93% (95% CI 79%-98%), the specificity was 44% (95%
      CI 41%-48%), and the negative predictive value was 99% (95% CI 92%-100%). There
      were significant associations between ETCO2 and serum bicarbonate levels (r =
      0.429, P < .001), anion gap (r = -0.216, P < .001), and lactate (r = -0.376, P <
      .001). CONCLUSION: Of all prehospital vital signs, ETCO2 was the most predictive
      and consistent for mortality, which may be related to an association with
      metabolic acidosis.

PMID- 24332901
TI  - ED, heal thyself.
AB  - Emergency department (ED) wait times have continued to worsen despite receiving
      considerable attention for more than 2 decades and despite the availability of a
      variety of methods to restructure care in a more streamlined fashion. This
      article offers an economic framework that abstracts away from the details of
      operations research to understand the fundamental disincentives to improving wait
      times. Hospitals that reduce wait times are financially penalized if they must
      provide more uncompensated care as a result. Pending changes under the Patient
      Protection and Affordable Care Act are considered. We find that the likely effect
      of the Patient Protection and Affordable Care Act's insurance expansion is to
      reduce this penalty for improving ED wait times. Consequently, mandating adoption
      of solutions to ED crowding may be unnecessary and counterproductive. If the
      insurance expansion is insufficient to fully solve the problem, the hospital
      value-based purchasing initiative should adopt wait times as a goal in its next
      iteration. 

PMID- 24332902
TI  - De Garengeot hernia: the ultrasound and computed tomographic findings in an 81
      year-old woman.
AB  - The presence of appendix within a femoral hernia is a rare condition in an
      incarcerated femoral hernia. It has a characteristic groin mass, and the
      diagnosis of appendicitis is mainly made intraoperatively. A specific imaging
      appearance (ultrasonography, computed tomography [CT]) allows accurate
      prospective diagnosis. The recognition of this rare femoral hernia helps us to
      choose appropriate therapeutic approach. We report a case of an 81-year-old woman
      who present with painful and nonreducible groin mass. The ultrasonography and CT
      characteristic imaging features successfully diagnosed de Garengeot hernia. To
      our knowledge, this is the first description of a combination of CT and
      ultrasound in the preoperative diagnosis.

PMID- 24332904
TI  - Spontaneous lingual abscess in an immunocompromised patient.
AB  - Acute lingual abscess is a rare yet life-threatening clinical entity. Lingual
      abscess must be appropriately diagnosed and treated in the emergency department
      to avoid acute airway compromise. A 68-year-old woman on immunomodulatory
      medication for rheumatoid arthritis presented to the emergency department with
      left facial pain and swelling. An anterior lingual abscess was diagnosed on
      computed tomographic scan. The most common cause of lingual abscess is direct
      trauma, although immunocompromised state is a predisposing risk factor.
      Intravenous antibiotics are the primary treatment modality, with consideration
      given to adjunctive surgical drainage. We present this case to increase awareness
      surrounding this diagnosis among emergency physicians. Spontaneous lingual
      abscess should be considered in immunocompromised patients who present to the
      emergency department with tongue pain and edema even in the absence of lingual
      trauma.

PMID- 24332903
TI  - Fourth-generation troponin I levels and complex coronary lesions in acute
      coronary syndromes.

PMID- 24332905
TI  - Competence assessment of pre-elementary school teachers before and after a
      pediatric basic life support course for lay rescuers.

PMID- 24332906
TI  - Stay and play eFAST or scoop and run eFAST? That is the question!
AB  - The concept that ultrasonography could be interesting in the prehospital setting
      and during the transfer of traumatized patients is not new. Paradoxically, there
      is a lack of description of routine use of ultrasonography in emergency
      ambulances. The aim of this study was to compare the feasibility and efficiency
      of an extended focused assessment sonography for trauma (eFAST) examination
      performed on-site, during the patient's transfer, or both. MATERIALS AND METHODS:
      From February 2010 to June 2012, 30 prehospital emergency physicians were divided
      randomly into 3 groups. Group 1 performed an ultrasound examination on-site;
      group 2, during patient transfer; and group 3, in both settings. The eFAST
      examination was systematically performed in all severe traumas. RESULTS: Ninety
      eight patients were included. Forty-four eFAST examinations were performed on
      site only; 33, only during transport; and 21, in both settings. The feasibility
      was 95.4%, 93.9%, and 95.2%, respectively, and efficiency, 95%, 97%, and 100%,
      respectively. There was no significant difference in performance or duration
      whether the examination was performed on-site, during the transfer, or both (w =
      0.68). Last but not least, in 2 cases in group 3, the second examination carried
      out during transfer showed new results with the occurrence of intraperitoneal
      effusion in one case and a pleural effusion in the other. CONCLUSIONS: The eFAST
      examination can provide reliable and important information in the initial
      evaluation of traumatized patients. It can be completed either on-site or during
      patient transfer. Its feasibility and efficiency are similar to that done in
      intensive units, especially if the examination is repeated.

PMID- 24332907
TI  - Supreme Laryngeal Mask Airway achieves faster insertion times than Classic LMA
      during chest compressions in manikins.
AB  - BACKGROUND: According to the 2010 European Resuscitation Council guidelines on
      cardiopulmonary resuscitation (CPR), one can appreciate that the classic
      laryngeal mask airway (CLMA) is acceptable as an alternative airway device to
      endotracheal intubation for airway management in cardiac arrest victims.
      OBJECTIVE: To compare a relatively new supraglottic airway device, the Supreme
      Laryngeal Mask Airway (SLMA), with the CLMA in a cardiac arrest scenario.
      METHODS: Fifty healthcare professionals inexperienced in advanced airway
      management attempted to insert both airway devices in a manikin in 2 scenarios:
      in the first, chest compressions were not performed (non-CPR scenario), and in
      the second, uninterrupted chest compressions were performed (CPR scenario). The
      primary end points were insertion time and success rate at first attempt. The
      level of self-confidence of each participant was recorded. RESULTS: SLMA achieves
      faster insertion times both in the non-CPR (SLMA: 10.4 +/- 2.7 seconds vs CLMA:
      13.4 +/- 3.2 seconds, P < .05) and in the CPR scenario (SLMA: 9.9 +/- 2.0 seconds
      Vs CLMA: 11.9 +/- 2.3 seconds, P < .05). The difference between first attempt
      success rates was not statistically significant both in the non-CPR (SLMA: 96% vs
      CLMA: 90%, P = .18) and in the CPR scenario (SLMA: 98% vs CLMA: 94%, P = .32).
      The participants are more self-confident using SLMA instead of CLMA (P < .001)
      and 94% of them would prefer SLMA for future use. CONCLUSION: SLMA could be a
      useful alternative to CLMA during CPR in the hands of healthcare professionals
      with minimal experience in airway management.

PMID- 24332908
TI  - Thrombotic events in Behcet's disease.

PMID- 24332909
TI  - Is the evaluation of the sublingual density of perfused capillaries in patients
      with heart failure a useful tool in the emergency ward?

PMID- 24332911
TI  - Pretreatment with P2Y12 inhibitors in non-ST-segment elevation acute coronary
      syndrome: Time to revise the guidelines?

PMID- 24332910
TI  - Urinalysis is an inadequate screen for rhabdomyolysis.
AB  - STUDY OBJECTIVES: Hematuria by urine dipstick with absent red blood cells (RBCs)
      on microscopy is indicative of rhabdomyolysis. We determined the sensitivity of
      this classic urinalysis (UA) finding in the diagnosis of rhabdomyolysis. METHODS:
      We conducted a retrospective electronic medical record review of patients with a
      primary or secondary diagnosis of rhabdomyolysis with a creatine phosphokinase
      (CPK) greater than 1000 IU/L and a UA within the first 24 hours. Data were
      collected using a standardized data form, and a blinded panel of 3 emergency
      medicine physicians reviewed selected cases. Sensitivity and 95% confidence
      intervals (CIs) were calculated for detection of rhabdomyolysis by UA. RESULTS:
      During the study period, 1796 patients were diagnosed with rhabdomyolysis, of
      whom 228 met inclusion criteria. The mean peak CPK was 27509 IU/L. One hundred
      ninety-five (86%) had a urine dip-positive for blood. However, only 94 patients
      (41%) had a positive urine dip and negative microscopic hematuria, resulting in a
      sensitivity of 41% (95% CI, 35%-47%). In a subset of 66 patients (29%) with more
      severe rhabdomyolysis (initial CPK, >=10000 IU/L; mean CPK, 53365 IU/L), UA had a
      sensitivity of 55% (95% CI, 43%-67%). Broadening the definition of negative
      microscopy from 0 to 3 RBCs to less than 10 RBCs only increased the sensitivity
      to 79% (95% CI, 73%-83%). CONCLUSIONS: The combination of a positive urine dip
      for blood and negative microscopy is an insensitive test for rhabdomyolysis, and
      the absence of this finding should not be used to exclude the diagnosis.

PMID- 24332912
TI  - MIBG myocardial scintigraphy in pre-motor Parkinson's disease: a review.
AB  - OBJECTIVES: Detecting very early markers of neurodegeneration that predate the
      diagnosis of idiopathic Parkinson's disease (PD) is a crucial research topic for
      the development of disease-modifying therapeutic interventions. Recently (123)I
      metaiodobenzylguanidine (MIBG) myocardial scintigraphy has become widely used for
      this purpose, since this test shows high sensitivity and specificity in the
      diagnosis of PD, based on evidence that cardiac sympathetic nerve fibers are
      affected early and commonly in PD. We reviewed the literature to determine the
      role of MIBG myocardial scintigraphy for diagnosing pre-motor PD. METHODS: We
      performed a systematic review of the literature to identify the use of MIBG
      myocardial scintigraphy in relation to the constellation of pre-motor symptoms in
      PD. RESULTS: Mild memory disorder, autonomic failure (constipation and postural
      hypotension), depression/anxiety, visual hallucination/psychosis (in the
      elderly), sleep disorder (REM sleep behavior disorder), and impaired olfaction
      are reported to appear as sole initial symptoms of PD. All clinical features
      except for impaired olfaction are accompanied by low MIBG uptake, suggestive of
      very early PD in situ. CONCLUSION: Identifying persons with mild memory disorder,
      constipation/postural hypotension, depression/anxiety, visual
      hallucination/psychosis (in the elderly), and REM sleep behavior disorder
      associated with low MIBG uptake may provide a unique opportunity to detect very
      early PD in situ within a pre-clinical window. Future prospective studies to
      investigate further the findings of these early cases are warranted.

PMID- 24332914
TI  - Late-onset neonatal sepsis, risk factors and interventions: an analysis of
      recurrent outbreaks of Serratia marcescens, 2006-2011.
AB  - BACKGROUND: Between 2006 and 2011, 11 patients with Serratia marcescens sepsis
      and 47 patients colonized due to the spread of various clones were observed.
      These recurrent clusters brought about interventions to reduce spread between
      patients. AIM: To evaluate the effect of stepwise interventions to prevent S.
      marcescens colonization/sepsis and to analyse risk factors for late-onset sepsis
      (LOS). METHODS: An open retrospective observational study was performed to
      evaluate the interventions. A retrospective case-control study was performed to
      analyse the risk factors for LOS. FINDINGS: S. marcescens sepsis and colonization
      decreased after the stepwise adoption of hygiene interventions. Low gestational
      age, low birth weight, indwelling central venous or umbilical catheter, and
      ventilator treatment were identified as risk factors for LOS. Compliance with
      basic hygiene guidelines was the only intervention monitored continuously from
      late 2007. Compliance increased gradually to a steady high level in early 2009.
      There was a decrease in S. marcescens LOS, clustering after the second quarter of
      2008. After the first quarter of 2009, S. marcescens colonization decreased.
      CONCLUSION: It was not possible to identify the specific effects of each
      intervention, but it is likely that an update of the hospital's antibiotic policy
      affected the occurrence of S. marcescens LOS. The delayed effect of interventions
      on S. marcescens colonization was probably due to the time it takes for new
      routines to have an effect, illustrated by the gradual increase in compliance
      with basic hygiene guidelines.

PMID- 24332915
TI  - Predictors of outcome for patients with lung adenocarcinoma carrying the
      epidermal growth factor receptor mutation receiving 1st-line tyrosine kinase
      inhibitors: Sensitivity and meta-regression analysis of randomized trials.
AB  - PURPOSE: We performed a sensitivity and meta-regression analysis, cumulating all
      randomized trials exploring the benefit of afatinib, erlotinib and gefitinib
      versus chemotherapy in advanced EGFR mutant NSCLC, to investigate the potential
      role of additional clinico-pathological predictors of TKIs efficacy. RESULTS:
      With regard to progression-free survival (PFS), a significant interaction
      according to ethnicity (Asian versus Caucasian versus mixed) and to trial design
      (retrospective versus prospective EGFR analysis), was found; a trend toward
      significance with regard to type of drug (gefitinib versus erlotinib versus
      afatinib) was determined. No statistically significant differences in survival
      were observed. With regard to response, a significant interaction according to
      ethnicity, trial design and type of drug, was found. CONCLUSION: These data,
      together with a deeper characterization of the molecular background sustaining
      the oncogenic process, may contribute to create a clinico-pathologic predictive
      model, aimed to improve the magnitude of benefit expected from the use of
      targeted agents.

PMID- 24332913
TI  - Collective invasion in breast cancer requires a conserved basal epithelial
      program.
AB  - Carcinomas typically invade as a cohesive multicellular unit, a process termed
      collective invasion. It remains unclear how different subpopulations of cancer
      cells contribute to this process. We developed three-dimensional (3D) organoid
      assays to identify the most invasive cancer cells in primary breast tumors.
      Collective invasion was led by specialized cancer cells that were defined by
      their expression of basal epithelial genes, such as cytokeratin-14 (K14) and p63.
      Furthermore, K14+ cells led collective invasion in the major human breast cancer
      subtypes. Importantly, luminal cancer cells were observed to convert
      phenotypically to invasive leaders following induction of basal epithelial genes.
      Although only a minority of cells within luminal tumors expressed basal
      epithelial genes, knockdown of either K14 or p63 was sufficient to block
      collective invasion. Our data reveal that heterotypic interactions between
      epithelial subpopulations are critical to collective invasion. We suggest that
      targeting the basal invasive program could limit metastatic progression. 

PMID- 24332916
TI  - Do placental lesions among term small for gestational age newborns differ
      according to the clinical presentation?
AB  - OBJECTIVE: To examine the incidence of placental lesions among women who
      delivered isolated small for gestational age newborns (isolated-SGA) at term
      compared to placentas from non-isolated-SGA born at term, early SGA and
      appropriate for age newborns (AGA). STUDY DESIGN: A case-control study conducted
      at a university teaching hospital. Placentas of women who delivered a newborn
      with a birthweight less than the 10th percentile were included. Group A (study
      group): isolated-SGA delivered at term. Group B (1st control group): Term SGA
      accompanied antepartum with oligohydramnios or maternal hypertension (non
      isolated-SGA). Group C (2nd control group): early SGA delivered before 34 weeks.
      Group D (3rd control group): placentas of low risk women who delivered AGA
      newborns at term. A total of 307 placentas were included: 72, 81, 60 and 94
      placentas from Groups A, B, C, and D respectively. The primary outcome was the
      incidence of placental lesions that characterize SGA. RESULTS: The most frequent
      placental lesion found among all groups was maternal obstructive lesions, which
      appeared in 45.8% and 45.7% of placentas from groups A and B respectively
      (p=0.98). The incidence among group A was significantly higher than in group D
      (20.2%) (p=0.0006) and lower than in group C (76.7%) (p=0.0004). The incidence of
      any placental lesion that characterized SGA among group A (69.4%) was 7.9 times
      higher than in group D (22.3%) (p<0.0001) and comparable to group B (61.7%)
      (p=0.3). The incidence of any placental lesion was highest among group C (83.3%).
      CONCLUSIONS: The incidence of placental lesions was comparable among term SGA
      regardless of whether isolated or not and significantly higher than among AGA
      newborns.

PMID- 24332917
TI  - Concussions in women.

PMID- 24332918
TI  - Akt1 expression and activity at different stages in experimental heart failure.
AB  - Loss of function or/and death of cardiomyocytes is one of the major contributing
      factors in the development of heart failure. Cytosolic Hsp60 can directly
      interact and regulate activation of some kinases and sequestrate certain
      proapoptotic molecules to avoid the cardiomyocyte apoptosis. We assumed that Akt1
      kinase, a downstream effector of PI3 kinase, can interact with Hsp60. Our aim was
      to clarify the interaction of Akt1 and Hsp60 and to investigate the Akt1
      expression in normal and failing hearts in acute and chronic stress. The
      experimental mouse models of inducible myocarditis and DCM-like pathology were
      developed in our laboratory. Akt1 and phospho-Akt1 (pS473) expression were
      studied by Western blot analysis. Co-immunoprecipitation method was used to test
      complex formation of Akt1 and Hsp60. The interaction of Hsp60 and Akt1 was
      detected for the first time by co-immunoprecipitation method in normal myocardium
      and under pathology as well. There were no significant changes in the level of
      Akt1 expression in both myocardia. At the same time we observed significant
      decrease in Akt1 phosphorylation at the final stage of DCM-like pathology but not
      at experimental myocarditis. The final stage of heart failure in mouse model of
      DCM-like pathology was characterized by reduced level of phospho-Akt1/Akt1
      (pS473; -26%; P<0.05), whereas no differences were found in total Akt1 protein
      content. We suggest a possible involvement of cytoplasmic Hsp60 in regulation of
      Akt1 activity at heart failure progression. 

PMID- 24332919
TI  - Mannitol and renal dysfunction after endovascular aortic aneurysm repair
      procedures: a randomized trial.
AB  - OBJECTIVE: Endovascular aortic aneurysm repair (EVAR) may result in deterioration
      of renal function. Mannitol has renovascular and antioxidant properties that
      could prove beneficial in this respect. DESIGN: A randomized prospective study.
      SETTING: Attikon University Hospital, single institution. PARTICIPANTS: Eighty
      six patients undergoing elective EVAR under regional anesthesia. METHODS:
      Patients received hydration alone (controls) or hydration plus mannitol (0.5
      g/kg). MEASUREMENTS AND MAIN RESULTS: Creatinine, serum cystatin-C, urine
      neutrophil-gelatinase-associated lipocalin (NGAL), albuminuria and serum urea
      were measured 24 hours and 72 hours after the procedure (baseline NGAL was
      measured in 19 randomly selected patients). Serum creatinine also was measured at
      the followup of the patients. Serum creatinine and cystatin-C were lower in the
      mannitol group at 24 hours postoperatively (creatinine, mannitol [n=43]; 1.07+/
      0.26 [CI95%: 0.99-1.15] v controls [n=43]; 1.20+/-0.30 [CI95%: 1.11-1.30]), but
      not at 72 hours (creatinine, mannitol [n=43]; 1.13+/-0.29 [CI95%: 1.04-1.22] v
      controls [n=43]; 1.26+/-0.41 [CI95% 1.15-1.38]). Urine NGAL increased
      substantially at 24 hours without differences between groups. At followup
      (controls: 13+/-7 months; mannitol: 12+/-7 months), there were no differences
      between creatinine or creatinine clearance (creatinine: controls [n=28]; 1.15+/
      0.39 [CI95% 1.02-1.29] v mannitol [n=23]; 1.05+/-0.27 [CI95%: 0.95-1.17]). The
      overall changes of creatinine and creatinine clearance with time were significant
      in controls but not in the mannitol group. The classification according to the
      RIFLE criteria yielded 4 patients at risk for renal injury and 2 with renal
      injury in the control group and 6 patients at risk with no patients with injury
      in the mannitol group, but the difference of renal dysfunction between the 2
      groups was not statistically significant. CONCLUSIONS: Mannitol plus hydration
      during EVAR provides a small but significant benefit for renal function. Future
      preventive protocols aiming at greater restoration of renal function after EVAR
      could include mannitol as a useful component.

PMID- 24332920
TI  - Anesthetic management of the resection of a Kommerell's diverticulum.

PMID- 24332921
TI  - Novel application of rapid prototyping for simulation of bronchoscopic anatomy.
AB  - OBJECTIVE: The authors used rapid prototyping (RP) technology to create
      anatomically congruent models of tracheo-bronchial tree for teaching relevant
      bronchoscopic anatomy. DESIGN: Pilot study. SETTING: A single level tertiary
      academic medical center. INTERVENTIONS: Two 3 dimensional (3D) models of tracheo
      bronchial tree (one showing normal anatomy and another with an early take off of
      right apical bronchus) were recreated from Computed Tomographic images using RP
      technology. These images were then attached to mannequins and examined with a
      flexible fiberoptic bronchoscope (FFB). These images were then compared with the
      actual FFB images obtained during lung isolation. MEASUREMENTS AND MAIN RESULTS:
      The images obtained through the 3D models were found to be congruent to actual
      patient anatomy. CONCLUSIONS: RP can be successfully used to create anatomically
      accurate models from imaging studies. There is potential for RP to become a
      valuable educational tool in the future.

PMID- 24332922
TI  - Echocardiography-based hemodynamic management in the cardiac surgical intensive
      care unit.

PMID- 24332924
TI  - Increased risk of alcohol dependency in a cohort of National Guard troops with
      PTSD: a longitudinal study.
AB  - Studies show high rates of co-morbid post-traumatic stress disorder (PTSD) and
      alcohol use disorder (AUD) but there is no consensus on the causal direction of
      the relationship. Some theories suggest AUD develops as a coping mechanism to
      manage PTSD symptoms and others that AUD is a vulnerability factor for PTSD. A
      third hypothesis posits independent developmental pathways stemming from a shared
      etiology, such as the trauma exposure itself. We examined these hypotheses using
      longitudinal data on 922 National Guard soldiers, representing a subsample (56%)
      of a larger pre- and post-deployment cross-sectional study of New Jersey National
      Guard soldiers deployed to Iraq. Measures included the PTSD Checklist (PCL), DSM
      IV-based measures of alcohol use/misuse from the National Household Survey of
      Drug Use and Health and other concurrent mental health, military and demographic
      measures. Results showed no effect of pre-deployment alcohol status on subsequent
      positive screens for new onset PTSD. However, in multivariate models, baseline
      PTSD symptoms significantly increased the risk of screening positive for new
      onset alcohol dependence (AD), which rose 5% with each unit increase in PCL score
      (AOR = 1.05; 95% CI = 1.02-1.07). Results also supported the shared etiology
      hypothesis, with the risk of a positive screen for AD increasing by 9% for every
      unit increase in combat exposure after controlling for baseline PTSD status (AOR
      = 1.09; 95% CI = 1.03-1.15) and, in a subsample with PCL scores <34, by 17% for
      each unit increase in exposure (AOR = 1.17; 95% CI = 1.05-1.31). These findings
      have implications for prevention, treatment and compensation policies governing
      co-morbidity in military veterans. 

PMID- 24332923
TI  - Oxidative stress in early stage Bipolar Disorder and the association with
      response to lithium.
AB  - BACKGROUND: Several studies have described increased oxidative stress (OxS)
      parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few
      is know about the impact of treatment at these targets. However, no study has
      evaluated OxS parameters in unmedicated early stage BD and their association with
      lithium treatment in bipolar depression. METHODS: Patients with BD I or II (n =
      29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples
      were collected at baseline and endpoint, and were also compared to age-matched
      controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the
      antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GPx) activities were measured. RESULTS: Subjects with BD depression
      at baseline presented a significant increase in CAT (p = 0.005) and GPx (p <
      0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or
      TBARS compared to healthy controls. Regarding therapeutics, lithium only induced
      a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII.
      Finally, TBARS levels were significantly lower at endpoint in lithium responders
      compared to non-responders (p = 0.018) with no difference in any biomarker
      regarding remission. CONCLUSION: The present findings suggest a reactive increase
      in antioxidant enzymes levels during depressive episodes in early stage BD with
      minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were
      observed, associated with lithium's clinical efficacy. Overall, these results
      reinforce the role for altered oxidative stress in the pathophysiology of BD and
      the presence of antioxidant effects of lithium in the prevention of illness
      progression and clinical efficacy.

PMID- 24332925
TI  - Polyurethane scaffold in lateral meniscus segmental defects: clinical outcomes at
      24 months follow-up.
AB  - BACKGROUND: Segmental tissue loss in the lateral meniscus is associated with pain
      and increased risk of osteoarthritis even when indications have been carefully
      considered. HYPOTHESIS: Repairing the defect using a novel biodegradable scaffold
      will reduce pain and restore the knee function. METHODS: In this prospective
      multicenter study, a total of 54 patients (37 males/17 females; mean age: 28
      years [16-50]) were enrolled. All patients presented with postmeniscectomy
      syndrome and segmental lateral meniscus loss, and were treated with a
      polyurethane biodegradable scaffold (Actifit((r)), Orteq) implanted
      arthroscopically. Clinical outcomes were assessed at 6, 12 and 24 months using
      Visual Analogue Scale (VAS), International Knee Documentation Committee Score
      (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: VAS
      decreased from 5.5 at baseline to 3.6 at 6 months, 3.4 at 12 months and 2.9 at 24
      months. IKDC improved from 47.0 at baseline to 60.2, 67.0 and 67.0 at 6, 12 and
      24 months. All KOOS subscores improved between baseline and 24 months.
      DISCUSSION: Clinical results of this study demonstrate clinically and
      statistically significant improvements of pain and function scores (VAS, IKDC,
      and all KOOS subscales except sport), at the 6 months follow-up and on all
      clinical outcomes at the 2-year follow-up. The Actifit((r)) scaffold is safe and
      effective in treating lateral meniscus defects. LEVEL OF EVIDENCE IV: continuous
      prospective multicenter study.

PMID- 24332927
TI  - The role of transforming growth factor (TGF)-beta in modulating the immune
      response and fibrogenesis in the gut.
AB  - Transforming growth factor (TGF)-beta, a pleiotropic cytokine released by both
      immune and non-immune cells in the gut, exerts an important tolerogenic action by
      promoting regulatory T cell differentiation. TGF-beta also enhances enterocyte
      migration and regulates extracellular matrix turnover, thereby playing a crucial
      role in tissue remodeling in the gut. In this review we describe the mechanisms
      by which abnormal TGF-beta signaling impairs intestinal immune tolerance and
      tissue repair, thus predisposing to the onset of immune-mediated bowel disorders,
      such as inflammatory bowel disease and celiac disease. Additionally, we will
      discuss potential therapeutic strategies aiming at restoring physiologic TGF-beta
      signaling in chronic intestinal diseases. 

PMID- 24332928
TI  - Daily supplementation with ghrelin improves in vitro bovine blastocysts formation
      rate and alters gene expression related to embryo quality.
AB  - Ghrelin is a gastric peptide having regulatory role in the reproductive system
      functionality, acting mainly at central level. Because the expression of ghrelin
      system (ghrelin and its receptor) has been detected in the bovine ovary, the
      objectives of the present study were to investigate whether ghrelin can affect
      the developmental potential of in vitro-produced embryos, and to test their
      quality in terms of relative abundance of various genes related to metabolism,
      apoptosis and oxidation. In the first experiment, in vitro-produced zygotes were
      cultured in the absence (control [C]) and in the presence of three concentrations
      of acylated ghrelin (200 pg/mL [Ghr200], 800 pg/mL [Ghr800]; and 2000 pg/mL
      [Ghr2000]); blastocyst formation rates were examined on Days 7, 8, and 9. In the
      second experiment, only the 800 pg/mL dose of ghrelin was used. Zygotes were
      produced as in experiment 1 and 24 hours post insemination they were divided into
      4 groups; in two groups (C; without ghrelin; Ghr800 with ghrelin), embryos were
      cultured without medium replacement; in the remaining two groups (Control N and
      GhrN), the culture medium was daily renewed. A pool of Day-7 blastocysts were
      snap frozen for relative mRNA abundance of various genes related to metabolism,
      oxidation, implantation, and apoptosis. In experiment 3, embryos were produced as
      in experiment 2, but in the absence of serum (semi-defined culture medium). In
      experiment 1, no differences were detected between C, Ghr200, and Ghr2000,
      although fewer blastocysts were produced in group Ghr800 compared with C. In
      experiment 2, the lowest blastocysts yield was found in Ghr800, whereas daily
      renewal of ghrelin (Ghr800N) resulted to increased blastocysts formation rate,
      which on Day 7 was the highest among groups (P < 0.05). In experiment 3, ghrelin
      significantly suppressed blastocysts yield. Significant differences were detected
      in various relative mRNA abundance, giving an overall final notion that embryos
      produced in the presence of ghrelin were of better quality than controls. Our
      results imply a specific role of ghrelin in early embryonic development; however,
      the specific mode of its action needs further investigation.

PMID- 24332929
TI  - Reconstruction of upper lip avulsion after dog bite: case report and review of
      literature.
AB  - IMPORTANCE: Upper lip avulsion after traumatic dog bite is a serious cause of
      facial disfigurement for which there is no consensus on management in the acute
      setting. OBJECTIVE: This review was prompted by a case at our institution and is
      intended to display the available evidence in the management of the patient after
      dog bite injury to the upper lip. Our main goals are to create a management
      algorithm using current evidence and to stimulate further clinical investigation
      to improve outcomes in patients with facial dog bite injuries. EVIDENCE REVIEW: A
      review of English literature was performed using Pubmed/MEDLINE for case reports
      and case series of lip replantation using microvascular anastomosis. Additional
      review of hyperbaric oxygen therapy, medicinal leech therapy, lip reconstruction
      methods, and reapproximation was performed. Reference searches were performed for
      all retrieved articles. FINDINGS: Microvascular replantation is a successful
      method of acute management in dog bite injuries of the lip. Hyperbaric oxygen
      therapy and medicinal leech therapy improve outcomes. Immediate cross-lip flaps
      and immediate reapproximation are alternative techniques that can be performed in
      the acute setting, but further investigation is required. CONCLUSIONS: The repair
      of the upper lip after a dog bite is a priority due to the functional and
      psychiatric sequelae associated with facial disfigurement. Microvascular
      replantation should be considered first-line. Immediate reapproximation without
      microvascular reanastomosis and immediate reconstruction may also be performed. A
      stepwise clinical algorithm may aid the surgeon in the acute management of dog
      bite trauma to the lip.

PMID- 24332930
TI  - Targeted proteomics for validation of biomarkers in early psychosis.

PMID- 24332926
TI  - Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning.
AB  - The regulation of vascular endothelial growth factor A (VEGF) is critical to
      neovascularization in numerous tissues under physiological and pathological
      conditions. VEGF has multiple isoforms, created by alternative splicing or
      proteolytic cleavage, and characterized by different receptor-binding and matrix
      binding properties. These isoforms are known to give rise to a spectrum of
      angiogenesis patterns marked by differences in branching, which has functional
      implications for tissues. In this review, we detail the extensive extracellular
      regulation of VEGF and the ability of VEGF to dictate the vascular phenotype. We
      explore the role of VEGF-releasing proteases and soluble carrier molecules on
      VEGF activity. While proteases such as MMP9 can 'release' matrix-bound VEGF and
      promote angiogenesis, for example as a key step in carcinogenesis, proteases can
      also suppress VEGF's angiogenic effects. We explore what dictates pro- or anti
      angiogenic behavior. We also seek to understand the phenomenon of VEGF gradient
      formation. Strong VEGF gradients are thought to be due to decreased rates of
      diffusion from reversible matrix binding, however theoretical studies show that
      this scenario cannot give rise to lasting VEGF gradients in vivo. We propose that
      gradients are formed through degradation of sequestered VEGF. Finally, we review
      how different aspects of the VEGF signal, such as its concentration, gradient,
      matrix-binding, and NRP1-binding can differentially affect angiogenesis. We
      explore how this allows VEGF to regulate the formation of vascular networks
      across a spectrum of high to low branching densities, and from normal to
      pathological angiogenesis. A better understanding of the control of angiogenesis
      is necessary to improve upon limitations of current angiogenic therapies. 

PMID- 24332931
TI  - Central visfatin potentiates glucose-stimulated insulin secretion and beta-cell
      mass without increasing serum visfatin levels in diabetic rats.
AB  - INTRODUCTION: Our previous study revealed that plasma visfatin levels were lower
      in pregnant women with gestational diabetes (GDM) than non-GDM independent of
      prepreganacy BMI. We examined whether central visfatin modulates energy and
      glucose homeostasis via altering insulin resistance, insulin secretion or islet
      morphometry in diabetic rats. METHODS: Partial pancreatectomized, type 2
      diabetic, rats were interacerbroventricularly infused with visfatin
      (100ng/rat/day, Px-VIS), visfatin+visfatin antagonist, CHS-828 (100MUg/rat/day,
      Px-VIS-ANT), or saline (control, Px-Saline) via osmotic pump, respectively, for
      4weeks. RESULTS: Central visfatin improved insulin signaling (pAkt->pFOXO-1) but
      not pSTAT3 in the hypothalamus. Central visfatin did not alter serum visfatin
      levels in diabetic rats whereas the levels were higher in non-diabetic rats than
      diabetic rats. Body weight at the 2nd week was lowered in the Px-VIS group due to
      decreased food intake in the first two weeks compared to the Px-Saline group and
      energy expenditure was not significantly different among the treatment groups of
      diabetic rats. Visfatin antagonist treatment nullified the central visfatin
      effect. Px-VIS increased whole body glucose disposal rates in euglycemic
      hyperinsulinemic clamp compared to Px-Saline and lowered hepatic glucose output,
      whereas Px-VIS-ANT blocked the visfatin effect on insulin resistance (P<0.05). In
      hyperglycemic clamp study, the area under the curve of insulin in first and
      second phase were significantly higher in the Px-VIS group than the Px-Saline
      group without modifying insulin sensitivity at the hyperglycemic state, whereas
      the increase in serum insulin levels was blocked in the Px-VIS-ANT group. Central
      visfatin also increased beta-cell mass by increasing beta-cell proliferation.
      CONCLUSIONS: Central visfatin improved glucose homeostasis by increasing insulin
      secretion and insulin sensitivity at euglycemia through the hypothalamus in
      diabetic rats. Therefore, visfatin is a positive modulator of glucose homeostasis
      by delivering the hypothalamic signals into the peripheries.

PMID- 24332933
TI  - Disclosing medical errors to patients: effects of nonverbal involvement.
AB  - OBJECTIVE: The purpose of this study was to test causal effects of physicians'
      nonverbal involvement on medical error disclosure outcomes. METHODS: 216 hospital
      outpatients were randomly assigned to two experimental treatment groups. The
      first group watched a video vignette of a verbally effective and nonverbally
      involved error disclosure. The second group was exposed to a verbally effective
      but nonverbally uninvolved error disclosure. All patients responded to seven
      outcome measures. RESULTS: Patients in the nonverbally uninvolved error
      disclosure treatment group perceived the physician's apology as less sincere and
      remorseful compared to patients in the involved disclosure group. They also rated
      the implications of the error as more severe, were more likely to ascribe fault
      to the physician, and indicated a higher intent to change doctors after the
      disclosure. CONCLUSION: The results of this study imply that nonverbal
      involvement during medical error disclosures facilitates more accurate patient
      understanding and assessment of the medical error and its consequences on their
      health and quality of life. PRACTICE IMPLICATIONS: In the context of disclosing
      medical errors, nonverbal involvement increases the likelihood that physicians
      will be able to continue caring for their patient. Thus, providers are advised to
      consider adopting this communication skill into their medical practice.

PMID- 24332932
TI  - Laparoscopic treatment of renal cancer in children: a multicentric study and
      review of oncologic and surgical complications.
AB  - OBJECTIVE: The aim was to report a multicentric study with a longer follow-up to
      evaluate the laparoscopic radical nephrectomy in children with renal cancer.
      MATERIAL AND METHODS: This was a retrospective multicentric study, from October
      2005 to January 2012, of children who underwent a laparoscopic radical
      nephrectomy for small renal malignant tumors. RESULTS: Seventeen children were
      included in this study. Sixteen underwent chemotherapy before surgery according
      the SIOP (Societe Internationale d'Oncologie Pediatrique) protocol and one was
      treated by surgery only for a carcinoma. All except one could be treated by
      laparoscopy; the biggest tumoral size was 8 cm. The median hospital stay was 3
      days (2-10). The pathologic examination showed 15 Wilms' tumors, one clear cell
      sarcoma and one TFE3 renal cell carcinoma. With a median follow-up of 42 months
      (range 12 and 77 months) after laparoscopic radical nephrectomy, 15 children had
      no oncological complications (port site or local recurrence, pulmonary
      metastasis) and one had a local recurrence without intraoperative tumoral
      rupture. The child with TFE3 renal cell carcinoma died 4 years after surgery from
      brain and lung metastases without local recurrence. No small bowel obstruction
      occurred. CONCLUSIONS: Radical nephrectomy in children for Wilms' tumor or other
      renal cancer can be safely performed laparoscopically and our indications can be
      summarized, for trained laparoscopic surgeons, by small tumors under about 8 cm
      diameter, especially without crossing the lateral edge of the vertebra on the CT
      scan at the time of surgery.

PMID- 24332934
TI  - Motivational cues as real-time feedback for changing daily activity behavior of
      patients with COPD.
AB  - OBJECTIVE: To investigate how COPD patients respond to motivational cues that aim
      to improve activity behavior and how these responses are related to cue- and
      context characteristics. In addition, to explore whether activity can be
      increased and better distributed over the day by providing such cues. METHODS:
      Fifteen COPD patients participated. Patients used an activity sensor with a
      smartphone for four weeks, at least four days/week. Patients received
      motivational cues every 2h with advice on how to improve their activity, on top
      of real-time visual feedback. The response was calculated by the amount of
      activity 30 min before and after a cue. RESULTS: In total, 1488 cues were
      generated. The amount of activity significantly decreased in the 30 min after a
      discouraging cue (p<0.001) and significantly increased (p<0.05) in the 10 min
      after an encouraging cue. The activity level increased with 13% in the
      intervention period compared to corrected baseline (p=0.008). The activity was
      not more balanced over the day. CONCLUSIONS: COPD patients significantly change
      their activity level in response to motivational cues, based on continuous
      ambulatory assessment of activity levels. PRACTICE IMPLICATIONS: Motivational
      cues could be a valuable component of telemedicine interventions that aim to
      improve activity behavior.

PMID- 24332935
TI  - Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation
      carriers: results from ten studies.
AB  - Although reproductive factors are among the most well-established risk factors
      for breast cancer in the general population, it is still a matter for debate
      whether these factors act as risk modifiers among BRCA1 or BRCA2 mutation
      carriers. This meta-analysis is the first to be performed to determine the
      relationship between reproductive factors and breast cancer risk among BRCA1 and
      BRCA2 mutation carriers. We searched the PubMed database up to February 2013. A
      total of ten studies met the inclusion criteria. The results showed that the
      reproductive factors may be associated with breast cancer risk only among BRCA1
      mutation carriers. No association was found between parity and breast cancer
      risk. Compared with women at the youngest age in the first-birth category, women
      in the oldest age category were at a 38% lower risk of breast cancer (RR=0.62,
      95%CI=0.45-0.85). Breastfeeding for at least 1 or 2 years was associated with a
      37% reduction in breast cancer risk (RR=0.63, 95%CI=0.46-0.86). Women at the
      oldest age in the menarche category were at a 34% lower risk of breast cancer
      (RR=0.66, 95%CI=0.53-0.81) than women in the youngest age category. However, none
      of the reproductive factors were associated with breast cancer risk among BRCA2
      mutation carriers. In conclusion, late age at first birth, breastfeeding, and
      late age at menarche protect against breast cancer in BRCA1 mutation carriers
      only. Further studies are needed to explore the mechanisms. 

PMID- 24332936
TI  - Coronary heart disease risk equivalence in diabetes and arterial diseases
      characterized by endothelial function and endothelial progenitor cell.
AB  - AIMS: Peripheral Arterial Disease (PAD), Carotid Artery Disease (CAD), and Type 2
      Diabetes Mellitus (DM) were considered as "Coronary Heart Disease (CHD) risk
      equivalents". Vascular endothelial dysfunction was recognized as an early event
      in the development of atherosclerosis. Involved in neovasculogenesis and
      maintenance of vascular homeostasis, endothelial progenitor cell (EPC) has been
      considered as a biological marker of cardiovascular disease. The purpose of this
      study was to assess the CHD risk equivalents concept by investigating the
      endothelial function and circulating EPC number in patients with CHD, PAD, CAD
      and T2DM. METHODS: There were four groups in the study: CHD (n = 19), AD [PAD and
      CAD (n = 17)], DM (n = 21) and healthy controls (HC, n = 20). PAD and CAD were
      assessed by ultrasonography. Coronal artery angiography was used to identify CHD.
      The diagnosis of T2DM was based on oral glucose tolerance test and medical
      history. Vascular endothelial function was assessed by flow-mediated brachial
      artery dilatation (FMD). Circulating EPC was quantified by flow cytometry.
      RESULTS: The circulating EPC numbers in four groups were CHD, 973 +/- 96; AD,
      1048 +/- 97; T2DM, 1210 +/- 125; HC, 1649 +/- 112 cells/ml. There were no
      significant differences in circulating EPC numbers between CHD and AD groups (P >
      0.05). Compared with CHD or AD group, T2DM group was associated with a slight
      increase in circulating EPC numbers (P < 0.05). The results of FMD were almost
      similar to the circulating EPC numbers(CHD, 4.06 +/- 0.54; AD, 3.90 +/- 0.48; DM,
      3.85 +/- 0.57; HC, 5.52 +/- 0.67%)except that there was no significant difference
      among the CHD, AD and T2DM groups (P > 0.05). Age, glycosylated hemoglobin, low
      density lipoprotein cholesterol, systolic blood pressure, body mass index (BMI)
      and medical history were the independent risk factors of circulating EPC number
      in all the patients (P < 0.05). Age, total cholesterol, BMI and medical history
      were the independent risk factors of FMD in all of the patients (P<0.05).
      CONCLUSIONS: The results of this study supported the equivalents hypothesis and
      revealed that "CHD risk equivalents" were characterized by the consistent
      physiological changes of blood vessels in angiogenesis, repairing ability and
      endothelial function.

PMID- 24332937
TI  - Relationship between circulating irisin, renal function and body composition in
      type 2 diabetes.
AB  - AIMS: Chronic kidney disease (CKD) secondary to type 2 diabetes mellitus (T2DM)
      is associated with multifaceted energy dysmetabolism. We aim to study the
      relationship between renal function, body composition and irisin, the recently
      identified myokine which is involved in energy regulation, in T2DM. METHODS:
      Circulating irisin and body composition were measured in 365 T2DM subjects across
      a wide range of renal function. RESULTS: Circulating irisin was significantly
      decreased in T2DM with renal insufficiency (77.4 +/- 13.7 ng/ml in T2DM with eGFR
      >= 60 ml/min/1.73 m(2) versus 72.5 +/- 14.9 ng/ml in those with eGFR<60
      ml/min/1.73 m(2), p = 0.001) and the reduction in irisin was most pronounced in
      stage 5 CKD patients. In T2DM with preserved renal function, irisin was
      correlated with age (r = -0.242, p = 0.001) and pulse pressure (r = -0.188, p =
      0.002). Among those with renal insufficiency, irisin was correlated with BMI (r =
      0.171, p = 0.022), fat mass (r = 0.191, p = 0.013), percentage of fat mass (r =
      0.210, p = 0.007) and eGFR (r = 0.171, p = 0.020). Multivariate linear regression
      models revealed that variations in circulating irisin were mainly attributable to
      eGFR and age in T2DM with and without renal impairment, respectively. CONCLUSION:
      Our observations suggest that the level of circulating irisin may be associated
      with renal function in T2DM. The role of reduced irisin in energy dysmetabolism
      in diabetic patients with renal insufficiency deserves further investigation.

PMID- 24332938
TI  - Aldose reductase, glucose and cataracts.

PMID- 24332939
TI  - The effect of U-74389G on pancreas ischemia-reperfusion injury in a swine model.
AB  - BACKGROUND: Oxidative stress is a crucial factor in the pathophysiology of acute
      pancreatitis and its systemic complications. Lazaroids are a novel class of
      antioxidants that potently protect pancreatic acinar cells against oxidant
      attack. The aim of our study was to evaluate the therapeutic potential of 21
      aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the
      organ in a swine model. MATERIALS AND METHODS: Twelve pigs (weighing 28-35 kg)
      were randomized into the following two experimental groups: group A (control
      group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min;
      and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous
      injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min.
      Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after
      reperfusion. Repeated measures analysis of variance was performed for the
      evaluation of differences between the two groups. RESULTS: Histopathologic
      evaluation did not reveal a statistically significant difference concerning
      hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P =
      0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two
      groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P
      = 0.020). Serum metabolic data in the control and therapy groups were not
      significantly different; accordingly, tissue malondialdehyde levels (P = 0.705)
      and tumor necrosis factor alpha values (P = 0.863) did not differ between the two
      groups. CONCLUSIONS: On the basis of the histologic data and the absence of
      reduction in the malondialdehyde and tumor necrosis factor alpha levels, it is
      concluded that the administration of U-74389G does not seem to exert a sizable
      therapeutic effect in attenuating pancreatic damage from ischemia-reperfusion
      injury.

PMID- 24332940
TI  - Carbohydrate-functionalized collagen matrices: design and characterization of a
      novel neoglycosylated biomaterial.
AB  - Collagen matrices have been neoglycosylated with lactose by reductive amination
      at lysine side chains. AFM analysis highlights that the chemical does not affect
      molecular assembly into fibrils. Moreover, ELLA biochemical assays show that the
      glycan moiety is efficiently exposed on the matrix surface for receptor
      recognition. 

PMID- 24332941
TI  - ATP sensitive bi-quinoline activator of the AMP-activated protein kinase.
AB  - The AMP-activated protein kinase (AMPK) regulates cellular and whole-body energy
      balance in response to changes in adenylate charge and hormonal signals.
      Activation of AMPK in tissues such as skeletal muscle and liver reverses many of
      the metabolic defects associated with obesity and Type 2 diabetes. Here we report
      a bi-quinoline (JJO-1) that allosterically activates all AMPK alphabetagamma
      isoforms in vitro except complexes containing the gamma3 subunit. JJO-1 does not
      directly activate the autoinhibited alpha subunit kinase domain and differs among
      other known direct activators of AMPK in that allosteric activation occurs only
      at low ATP concentrations, and is not influenced by either mutation of the gamma
      subunit adenylate-nucleotide binding sites or deletion of the beta subunit
      carbohydrate-binding module. Our findings indicate that AMPK has multiple modes
      of allosteric activation that may be exploited to design isoform-specific
      activators as potential therapeutics for metabolic diseases. 

PMID- 24332942
TI  - Bipolar nanosecond electric pulses are less efficient at electropermeabilization
      and killing cells than monopolar pulses.
AB  - Multiple studies have shown that bipolar (BP) electric pulses in the microsecond
      range are more effective at permeabilizing cells while maintaining similar cell
      survival rates as compared to monopolar (MP) pulse equivalents. In this paper, we
      investigated whether the same advantage existed for BP nanosecond-pulsed electric
      fields (nsPEF) as compared to MP nsPEF. To study permeabilization effectiveness,
      MP or BP pulses were delivered to single Chinese hamster ovary (CHO) cells and
      the response of three dyes, Calcium Green-1, propidium iodide (PI), and FM1-43,
      was measured by confocal microscopy. Results show that BP pulses were less
      effective at increasing intracellular calcium concentration or PI uptake and
      cause less membrane reorganization (FM1-43) than MP pulses. Twenty-four hour
      survival was measured in three cell lines (Jurkat, U937, CHO) and over ten times
      more BP pulses were required to induce death as compared to MP pulses of similar
      magnitude and duration. Flow cytometry analysis of CHO cells after exposure (at
      15 min) revealed that to achieve positive FITC-Annexin V and PI expression, ten
      times more BP pulses were required than MP pulses. Overall, unlike longer pulse
      exposures, BP nsPEF exposures proved far less effective at both membrane
      permeabilization and cell killing than MP nsPEF.

PMID- 24332943
TI  - FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in
      human granulosa cell tumors.
AB  - Human granulosa cell tumors (GCTs) are rare, and their etiology remains largely
      unknown. Recently, the FOXL2 402C>G (C134W) mutation was found to be specifically
      expressed in human adult-type GCTs; however, its function in the development of
      human GCTs is not fully understood. Activins are members of the transforming
      growth factor-beta superfamily, which has been shown to stimulate normal
      granulosa cell proliferation; however, little is known regarding the function of
      activins in human GCTs. In this study, we examined the effect of activin A on
      cell proliferation in the human GCT-derived cell line KGN. We show that activin A
      treatment stimulates KGN cell proliferation. Treatment with the activin type I
      receptor inhibitor SB431542 blocks activin A-stimulated cell proliferation. In
      addition, our results show that cyclin D2 is induced by treatment with activin A
      and is involved in activin A-stimulated cell proliferation. Moreover, the
      activation of Smad signaling is required for activin A-induced cyclin D2
      expression. Finally, we show that the overexpression of the wild-type FOXL2 but
      not the C134W mutant FOXL2 induced follistatin production. Treatment with
      exogenous follistatin blocks activin A-stimulated cell proliferation, and the
      overexpression of wild-type FOXL2 attenuates activin A-stimulated cell
      proliferation. These results suggest that FOXL2 may act as a tumor suppressor in
      human adult-type GCTs by inducing follistatin expression, which subsequently
      inhibits activin-stimulated cell proliferation. 

PMID- 24332944
TI  - Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of
      peroxisome proliferated activated receptor-gamma in patients with triglyceride
      deposit cardiomyovasculopathy.
AB  - Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule
      for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a
      rare multi-systemic neutral lipid storage disease. Information regarding its
      clinical profile and pathophysiology, particularly for cardiac involvement, is
      still very limited. A previous middle-aged ATGL-deficient patient in our
      institute (Case 1) with severe heart failure required cardiac transplantation
      (CTx) and exhibited a novel phenotype, "Triglyceride deposit
      cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism
      underlying TGCV. The subjects were two cases with TGCV, including our second case
      who was a 33-year-old male patient (Case 2) with congestive heart failure
      requiring CTx. Case 2 was homozygous for a point mutation in the 5' splice donor
      site of intron 5 in the ATGL, which results in at least two types of mRNAs due to
      splicing defects. The myocardium of both patients (Cases 1 and 2) showed up
      regulation of peroxisome proliferated activated receptors (PPARs), key
      transcription factors for metabolism of long chain fatty acids (LCFAs), which was
      in contrast to these molecules' lower expression in ATGL-targeted mice. We
      investigated the intracellular metabolism of LCFAs under human ATGL-deficient
      conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient
      cells showed higher uptake and abnormal intracellular transport of LCFA,
      resulting in massive TG accumulation. We used these findings from cardiac
      specimens and cell-biological experiments to construct a hypothetical model to
      clarify the pathophysiology of the human disorder. In patients with TGCV, even
      when hydrolysis of intracellular TG is defective, the marked up-regulation of
      PPARgamma and related genes may lead to increased uptake of LCFAs, the substrates
      for TG synthesis. This potentially vicious cycle of LCFAs could explain the
      massive accumulation of TG and severe clinical course for this rare disease. 

PMID- 24332945
TI  - Interleukin 2 receptor alpha chain gene polymorphisms and risks of multiple
      sclerosis and neuromyelitis optica in southern Japanese.
AB  - BACKGROUND: Interleukin 2 receptor alpha subunit (IL2RA) is a genetic risk for
      multiple sclerosis (MS) in Caucasians. However, the association between MS and
      IL2RA in Japanese idiopathic demyelinating diseases of the central nervous system
      has not been examined. OBJECTIVE: To determine whether IL2RA gene polymorphisms
      confer risks of developing MS or neuromyelitis optica (NMO) in a Japanese
      population. METHODS: DNA samples were obtained from 115 MS patients, 75 NMO/NMO
      spectrum disorder (NMOSD) patients, and 238 healthy controls. The single
      nucleotide polymorphisms (SNPs) rs2104286, rs12722489, and rs7090512 were
      genotyped by real-time PCR using TaqMan SNP genotyping assays. RESULTS: No
      significant associations of the three IL2RA SNPs with the development of the
      diseases were observed. In MS patients only, the annualized relapse rates were
      significantly higher for the rs2104286-TT genotype than for the non-TT (CT+CC)
      genotype and for the rs12722489-CC genotype than for the non-CC genotype in
      females (p = 0.0138 for both), but not in males. CONCLUSIONS: Although the
      possibility that IL2RA is a risk factor for MS development was not confirmed in
      this Japanese population, IL2RA gene polymorphisms were able to modify the
      disease activity in female MS patients, but had no influence on either
      susceptibility or disease phenotype in NMO/NMOSD patients.

PMID- 24332946
TI  - Exome sequencing reveals a novel MRE11 mutation in a patient with progressive
      myoclonic ataxia.
AB  - Progressive myoclonic ataxia (PMA) is a clinical syndrome defined as progressive
      ataxia and myoclonus and infrequent seizures in the absence of progressive
      dementia. Due to the extremely heterogeneous nature of PMA, a large proportion of
      PMA cases remain molecularly undiagnosed. The aim of this study was to clarify
      the molecular etiology of PMA. The patient was a 52-year-old female from
      consanguineous parents. She developed a jerking neck movement at age 9, which
      gradually expanded to her entire body. On physical examination at age 47, she
      exhibited generalized, spontaneous myoclonus that occurred continuously. She also
      presented with mild limb and truncal ataxia. An electroencephalogram revealed no
      abnormalities. A brain MRI displayed no atrophy of the cerebellum.
      Electrophysiological studies suggested myoclonus of a subcortical origin. For
      further evaluation, we performed exome sequencing, and we identified a novel
      homozygous missense mutation in the MRE11 gene (NM_005590:c.140C>T:p.A47V).
      Subsequently, we analyzed the expression of MRE11 and related proteins (RAD50 and
      NBS1) via Western blot, and they were markedly decreased compared to a healthy
      control. Mutations in the MRE11 gene have been known to cause an ataxia
      telangiectasia-like (ATLD) disorder. Accumulating evidence has indicated that its
      wide phenotypic variations in ATLD correspond to genotypic differences.
      Interestingly, our case exhibited a relatively mild decrease in NBS1 compared to
      previously reported cases of a homozygous missense mutation, which may account
      for the milder phenotype in this patient. Moreover, together with a recently
      reported case of an MRE11 mutation, it is suggested that MRE11 mutations can
      present as PMA. 

PMID- 24332947
TI  - Anorectal and sexual functions after preoperative radiotherapy and full-thickness
      local excision of rectal cancer.
AB  - AIMS: Local excision with preoperative radiotherapy may be considered as
      alternative management to abdominal surgery alone for small cT2-3N0 tumours.
      However, little is known about anorectal and sexual functions after local
      excision with preoperative radiotherapy. Evaluation of this issue was a secondary
      aim of our previously published prospective multicentre study. METHODS:
      Functional evaluation was based on a questionnaire completed by 44 of 64 eligible
      disease-free patients treated with preoperative radiotherapy and local excision.
      Additionally, ex post, these results were confronted with those recorded
      retrospectively in the control group treated with anterior resection alone (N =
      38). RESULTS: In the preoperative radiotherapy and local excision group, the
      median number of bowel movements was two per day, incontinence of flatus occurred
      in 51% of patients, incontinence of loose stool in 46%, clustering of stools in
      59%, and urgency in 49%; these symptoms occurred often or very often in 11%-21%
      of patients. Thirty-eight per cent of patients claimed that their quality of life
      was affected by anorectal dysfunction. Nineteen per cent of men and 20% of women
      claimed that the treatment negatively influenced their sexual life. The anorectal
      functions in the preoperative radiotherapy and local excision group were not much
      different from that observed in the anterior resection alone group. CONCLUSIONS:
      Our study suggests that anorectal functions after preoperative radiotherapy and
      local excision may be worse than expected and not much different from that
      recorded after anterior resection alone. It is possible that radiotherapy
      compromises the functional effects achieved by local excision.

PMID- 24332948
TI  - A meta-analysis of STAT3 and phospho-STAT3 expression and survival of patients
      with non-small-cell lung cancer.
AB  - BACKGROUND: The prognostic role of signal transducer and activator of
      transcription 3 (STAT3) and phospho-STAT3 in non-small-cell lung cancer (NSCLC)
      remains controversial. To clarify its impact on survival, we performed a meta
      analysis to quantitatively assess STAT3 and phospho-STAT3 expression on the
      prognosis of NSCLC. METHODS: Published studies were identified using a systematic
      and thorough literature search. To be eligible, a study had to investigate STAT3
      or phospho-STAT3 expression rates of NSCLC patients in different characteristics
      and provide patient survival data. RESULTS: A total of 17 retrospective trials
      were chosen for meta-analysis, including 1793 patients. The estimated pooled log
      HR (0.67, 95% CI: 0.57-0.77) of 9 trials (STAT3: log HR 0.71, 95% CI 0.38-1.04;
      phospho-STAT3: log HR 0.67, 95% CI 0.56-0.77) for NSCLC was statistically
      significant (P < 0.0001), suggesting that high STAT3 or phospho-STAT3 expression
      is a strong predictor of poor prognosis among patients with NSCLC. For the risk
      factors, pooled analysis of patients with STAT3 positivity, demonstrated a
      statistically significant OR (3.82, 95% CI: 2.37-6.16) between poorly
      differentiated carcinoma and well-moderately, OR (5.68, 95% CI: 3.16-10.21)
      between stage III-IV patients and stage I-II patients, and OR (3.41, 95% CI: 2.12
      5.49) between patients with lymph node metastasis and patients without lymph node
      metastasis. However, pooled analysis of patients with phospho-STAT3 positivity
      only demonstrated a statistically significant OR (4.51, 95% CI: 1.57-12.96)
      between poorly differentiated carcinoma and well-moderately (P < 0.05).
      CONCLUSIONS: High STAT3 or phospho-STAT3 expression is a strong predictor of poor
      prognosis among patients with NSCLC. The conclusion should be confirmed by large
      prospective studies with long-term follow-up.

PMID- 24332949
TI  - Dietary omega-3 fatty acids enhance the B1 but not the B2 cell immune response in
      mice with antigen-induced peritonitis.
AB  - The effects of omega-3 fatty acids on the adaptive immune response have mainly
      been analysed in vitro with varying results. How omega-3 fatty acids affect the
      adaptive immune response in vivo is largely unknown. This study examined the
      effects of dietary fish oil on the adaptive immune response in antigen-induced
      inflammation in mice, focusing on its effects on B cells and B cell subsets. Mice
      were fed a control diet with or without 2.8% fish oil, immunized twice with
      methylated BSA (mBSA) and peritonitis induced by intraperitoneal injection of
      mBSA. Serum, spleen and peritoneal exudate were collected prior to and at
      different time points after induction of peritonitis. Serum levels of mBSA
      specific antibodies were determined by ELISA and the number of peritoneal and
      splenic lymphocytes by flow cytometry. The levels of germinal center B cells and
      IgM(+), IgG(+) and CD138(+) cells in spleen were evaluated by immunoenzyme
      staining. Mice fed the fish oil diet had more peritoneal B1 cells, more IgM(+)
      cells in spleen and higher levels of serum mBSA-specific IgM antibodies compared
      with that in mice fed the control diet. However, dietary fish oil did not affect
      the number of peritoneal B2 cells, splenic IgG(+) or CD138(+) cells or serum
      levels of mBSA-specific IgG antibodies in mice with mBSA-induced peritonitis.
      These results indicate that dietary fish oil can enhance the adaptive immune
      response, specifically the B1 cell response, which may lead to better protection
      against secondary infection as well as improvement in reaching homeostasis
      following antigenic challenge. 

PMID- 24332950
TI  - Nonstandard glenoid components for bone deficiencies in shoulder arthroplasty.
AB  - BACKGROUND: Glenoid bone deficiencies may be addressed by specialized components.
      The purpose of this study is to evaluate the clinical and radiographic outcomes
      of 3 different types of nonstandard glenoid components. MATERIALS AND METHODS:
      Thirty-eight patients with a mean age of 65 years (range, 34-84 years) underwent
      a primary or revision anatomic shoulder arthroplasty with one of 3 nonstandard
      glenoid components: a polyethylene component with an angled keel for posterior
      glenoid wear without posterior subluxation; a polyethylene component with 2 mm of
      extra thickness for central glenoid erosion; or a posteriorly augmented metal
      backed glenoid component for posterior glenoid wear and posterior subluxation.
      Average clinical follow-up was 7.3 years (range, 2-19 years) or until revision
      surgery. RESULTS: At the most recent follow-up, 24 patients had no, mild, or
      occasionally moderate pain. Mean elevation improved from 91 degrees  to 126
      degrees , and mean external rotation improved from 24 degrees  to 53 degrees .
      Thirteen patients had moderate or severe subluxation preoperatively, and 11 had
      subluxation at follow-up. On radiographic evaluation, 3 glenoid components had
      loosened and 3 were at risk for loosening at an average 5.5 years of follow-up.
      Seven patients had revision surgery: 4 for instability, 1 for osteolysis, 1 for
      component loosening with osteolysis, and 1 for a periprosthetic fracture. Three
      additional patients had removal of glenoid components, 2 for infection and 1 for
      loosening. Ten-year survival rate free of revision or removal of the angled keel
      component was 73% (95% CI: 75.3-70.7); of the extra thick (+2 mm) component, 69%
      (95% CI: 65-73); and of the posteriorly augmented metal-backed glenoid component,
      31% (95% CI: 35.6-26.4). CONCLUSIONS: The effectiveness of nonstandard glenoid
      components in addressing glenoid bone deficiencies is compromised by an increased
      rate of component loosening and by only partial success in eliminating
      subluxation.

PMID- 24332951
TI  - Surgical fixation of extra-articular distal humerus fractures with a
      posterolateral plate through a triceps-reflecting technique.
AB  - BACKGROUND: Surgical management of extra-articular distal humerus fractures
      results in predictable fracture alignment. Open reduction and internal fixation
      also decrease the soft tissue complications and frequent follow-up required with
      functional bracing. A triceps-reflecting posterior approach provides excellent
      exposure to the humerus and minimizes trauma to the triceps. An anatomically
      precontoured plate on the posterolateral surface of the humerus provides stable
      fixation of these injuries and is placed directly through the interval developed
      by the triceps-reflecting approach. METHODS: We retrospectively reviewed the
      trauma databases at 2 level I academic trauma institutions during a 5-year period
      for all patients with an extra-articular distal humerus fracture treated with a
      triceps-reflecting approach and an anatomically precontoured posterolateral
      distal humerus plate. Patient and fracture characteristics were recorded, as were
      QuickDASH functional scores and visual analog scale scores for pain, function,
      and quality of life. RESULTS: Forty patients were eligible for our study. Average
      follow-up was 88 weeks. Thirty-eight (95%) patients went on to union. Seven (20%)
      patients required a secondary procedure. The average QuickDASH score was 17.5
      (range, 2.6-56.8). The average visual analog scale scores were 1.9 (range, 0-7)
      for pain, 2.3 (range, 0-8) for function, and 1.6 (range, 0-5) for quality of
      life. Thirty-five (87.5%) patients reported satisfaction with the outcome of
      their surgery. DISCUSSION: Surgical fixation of extra-articular distal humerus
      fractures through a triceps-reflecting approach with an anatomically precontoured
      posterolateral distal humerus plate results in predictable osseous union and
      overall excellent functional results for patients with this injury.

PMID- 24332952
TI  - Structural bone grafting for glenoid deficiency in primary total shoulder
      arthroplasty.
AB  - BACKGROUND: Glenoid bone grafting can be useful to restore an asymmetrically
      eroded glenoid to better support the glenoid component and improve positioning.
      The purpose of this study was to evaluate the clinical and radiographic results
      of patients undergoing structural bone grafting for glenoid deficiency with
      placement of a cemented glenoid component during primary total shoulder
      arthroplasty. METHODS: Between January 1, 1976, and December 31, 2008, 24
      patients (25 shoulders) of 2607 shoulders undergoing primary total shoulder
      arthroplasty (0.96%) had structural bone grafting with a humeral head autograft
      and screw fixation. The mean clinical follow-up was 8.7 years, and the mean
      radiographic follow-up was 7.6 years. RESULTS: Twenty-three shoulders experienced
      pain relief, and patients expressed satisfaction with the operation in these
      shoulders. Postoperative active elevation averaged 148 degrees , and external
      rotation with the arm at the side averaged 60 degrees . On radiographic
      evaluation, 10 shoulders had glenoids at risk for component loosening. Two of
      these shoulders were symptomatic and underwent revision surgery to address
      glenoid component loosening. The Neer result rating was excellent in 18
      shoulders, satisfactory in 5, and unsatisfactory in the 2 shoulders undergoing
      revision. CONCLUSION: Structural bone grafting in primary total shoulder
      arthroplasty is uncommonly necessary. When it is performed, the clinical outcomes
      are favorable; however, radiographic analysis shows a moderate rate of failure of
      glenoid component fixation. It seems likely that alternative treatment methods
      may prove to be more effective in addressing glenoid wear.

PMID- 24332953
TI  - Elbow arthroscopy: early complications and associated risk factors.
AB  - BACKGROUND: Elbow arthroscopy is increasingly used to treat complex pathology.
      The purpose of this study was to investigate early complication rates after elbow
      arthroscopy and identify risk factors for adverse events. METHODS: Consecutive
      elbow arthroscopies performed during a 13-year period were reviewed, identifying
      early perioperative complications. Major complications included deep infection,
      permanent nerve injury, or complications requiring additional anesthesia. Minor
      complications included superficial wound complications and transient nerve
      palsies. Complications were compared with a surgical complexity scale based on
      the procedure performed, the number of arthroscopic portals, and tourniquet time.
      RESULTS: Of 417 procedures, there were 37 minor (8.9%) and 20 major (4.8%)
      complications. The rates of superficial and deep infections were 6.7% and 2.2%,
      respectively. Major complications included 9 deep infections, 6 cases of
      heterotopic ossification requiring further surgery, and 4 manipulations under
      anesthesia. There were 7 transient sensory nerve complications, and no motor
      deficits. No differences in complication rates were seen between low-, moderate-,
      and high-complexity (10.2%, 16.3% and 14.4%, respectively) cases. Intraoperative
      steroid injections were strongly associated with postoperative superficial (14.1%
      vs 2.0%) and deep infection (4.9% vs 0.4%) in elbows receiving vs those not
      receiving steroid (P < .0001). CONCLUSIONS: Complications of elbow arthroscopy
      are seen in approximately 14% of cases. Most complications are minor, not
      affecting clinical outcome. Major complications occur in 5% of cases, often
      requiring repeat surgery. Intraoperative postsurgical steroid injections are
      associated with increased risk of perioperative infections. Case complexity does
      not appear to affect the rate of complications with modern surgical techniques.

PMID- 24332954
TI  - Secondary breast angiosarcoma: multifocal recurrence in a postmastectomy breast
      reconstruction flap.

PMID- 24332955
TI  - Ureteroinguinal hernia.

PMID- 24332956
TI  - Iliac branches of aortic endoprosthesis: Another long-lasting alternative for the
      treatment of popliteal aneurysms.

PMID- 24332957
TI  - [Use and versatility of titanium for the reconstruction of the thoracic wall].
AB  - INTRODUCTION: Chest wall deformities/defects and chest wall resections, as well
      as complex rib fractures require reconstruction with various prosthetic materials
      to ensure the basic functions of the chest wall. Titanium provides many features
      that make it an ideal material for this surgery. The aim is to present our
      initial results with this material in several diseases. MATERIAL AND METHODS:
      From 2008 to 2012, 14 patients were operated on and titanium was used for
      reconstruction of the chest wall. A total of 7 patients had chest wall tumors, 2
      with sternal resection, 4 patients with chest wall deformities/defects and 3
      patients with severe rib injury due to traffic accident. RESULTS: The
      reconstruction was successful in all cases, with early extubation without
      detecting problems in the functionality of the chest wall at a respiratory level.
      Patients with chest wall tumors including sternal resections were extubated in
      the operating room as well as the chest wall deformities. Chest trauma cases were
      extubated within 24h from internal rib fixation. There were no complications
      related to the material used and the method of implementation. CONCLUSIONS:
      Titanium is an ideal material for reconstruction of the chest wall in several
      clinical situations allowing for great versatility and adaptability in different
      chest wall reconstructions.

PMID- 24332958
TI  - Establishing research in a palliative care clinical setting: perceived barriers
      and implemented strategies.
AB  - There are many challenges in developing research projects in research-naive
      clinical settings, especially palliative care where resistance to participate in
      research has been identified. These challenges to the implementation of research
      are common in nursing practice and are associated with attitudes towards research
      participation, and some lack of understanding of research as a process to improve
      clinical practice. This is despite the professional nursing requirement to
      conduct research into issues that influence palliative care practice. The purpose
      of this paper is to describe the process of implementing a clinical research
      project in collaboration with the clinicians of a palliative care community team
      and to reflect on the strategies implemented to overcome the challenges involved.
      The challenges presented here demonstrate the importance of proactively
      implementing engagement strategies from the inception of a research project in a
      clinical setting. 

PMID- 24332959
TI  - Variations in the expression of vasotocin and isotocin receptor genes in the
      gilthead sea bream Sparus aurata during different osmotic challenges.
AB  - The dynamic changes in mRNA expression levels for vasotocin (AVT) and isotocin
      (IT) receptor gene levels were assessed in a time-course response study in
      immature male specimens of the gilthead sea bream (Sparus aurata) submitted to
      hyper- (550/00 salinity) and hypo-osmotic (50/00 salinity) challenges. Two
      different cDNAs for the AVT receptor and one for the IT receptor (V1a2-type and
      V2-type AVTR, and ITR, respectively) were cloned by screening an S. aurata brain
      cDNA library. Genes for these receptors were expressed differentially and is
      nearly ubiquitously in 26 of the examined tissues. In the gills, both
      environmental salinity challenges up-regulated AVTR V1a2-type gene expression
      concomitantly with mRNA expression protein activity of Na(+), K(+)-ATPase gene
      expression and protein, whereas the AVTR V2-type and cystic fibrosis
      transmembrane conductance regulator (CFTR) mRNA levels were associated with mRNAs
      environmental salinity, indicating a possible connection between AVTRs and these
      transporters. In kidney, AVTR V1a2-type gene expression peaked rapidly and lasted
      only a short time (12-24h) in response to both osmotic challenges. In contrast,
      AVTR V2-type mRNA levels were enhanced in specimens exposed to hyperosmotic
      conditions, whereas they decreased under hypoosmotic environments, suggesting an
      antidiuretic role related to the vasoconstriction function. In the hypothalamus,
      only the expression of the AVTR V2-type gene was enhanced at 7 and 14 days under
      both experimental conditions. In the liver, both AVTRs had increased mRNA levels,
      with the upregulation of their AVTR V2-type gene increasing faster than the V1a2
      type. The ITR gene was not sensitive to variations of external salinity in any of
      the analyzed tissues. Our results demonstrate the involvement of the
      vasotocinergic, but not the isotocinergic, pathway as well as the hypothalamic
      function, in the adjustments of both osmoregulatory and metabolic processes after
      osmotic challenges.

PMID- 24332960
TI  - Assessment of a hands-on method for FAMACHA(c) system training.
AB  - The FAMACHA((c)) system is a method for selective anthelmintic treatment
      comprising early detection of haemonchosis in sheep and goats. In order to
      evaluate the hands-on training methodology and the learning level of the
      participants, we analyzed data from 30 training events involving 47 training
      classes conducted in the State of Parana, Brazil, from July/2009 to May/2011,
      during which period a total of 1004 participants did 20,080 FAMACHA((c))
      classifications. In the practical training sessions, each participant
      individually evaluated 20 animals with known haematocrit values. Every
      participant per training event was given a unique number, whereupon each of the
      animals in a given event was FAMACHA((c)) classified by all the trainees
      involved, in the same trainee number sequence. After each consecutive animal had
      been evaluated by every one of the participants, its haematocrit and
      corresponding FAMACHA((c)) category were announced before the next animal was
      presented. The number of persons in training, which ranged from 5 to 39 per
      session, did not significantly affect the average error of the groups of
      participants involved (p>0.05). The average error in the classification of the
      first animal on a scale with a perfect score of zero was 2.5, significantly
      greater than the error of 0.56 of the twentieth one (p<0.05), indicating an
      inverse relationship between the error and the cumulative number of animals
      already evaluated by each trainee involved, with the reduction in mean error per
      animal in a given training event found by linear regression to be 0.0713. When
      the same animal was assessed twice in the same training event, the average error
      of the second evaluation (1.05) was significantly lower than the 1.70 of the
      first (p<0.05). While the total of 686 sheep used in the training events (73%)
      was considerably larger than the corresponding number of 254 goats (27%), the
      average statistical errors, respectively, 1.34 and 1.23, were not significantly
      different (p>0.05). Similarly, the average errors in FAMACHA((c)) classification
      were not significantly influenced by the occupation or gender of the
      participants, nor whether there were animals in all five FAMACHA((c)) categories
      or only in categories 1, 2, 3 and 4 per training event (p>0.05). 

PMID- 24332961
TI  - Occurrence of Toxoplasma gondii antibodies in birds from the Atlantic Forest,
      state of Sao Paulo, Brazil.
AB  - Avian are considered important intermediate hosts for Toxoplasma gondii because
      they serve as source of infection for Felidae, which shed environmentally
      resistant oocysts after ingesting infected tissues. Little is known of
      epidemiology of toxoplasmosis in wild birds. In the present study, antibodies to
      T. gondii were determined in 202 wild birds of 37 species captured in seven small
      areas of the Atlantic Forest, in the state of Sao Paulo, Brazil, and provided
      information on possible associated risk factors. Antibodies to T. gondii were
      assayed by the modified agglutination test (MAT) and found in 73 (36.1%) of 202
      birds with titers of 1:5 in 16 samples, 1:10 in 26 samples, 1:20 in 17 samples,
      1:40 in 10 samples, 1:80 in three samples, and 1:160 in one sample. No
      association was observed between T. gondii seropositivity and the local where the
      birds were collected. Seropositivity was higher in birds that lived on the forest
      floor (p<0.001; U=1230.0), and in omnivorous birds (p=0.007; U=3939.0). T. gondii
      antibodies were reported for the first time in 23 species of birds enlarging the
      host range of this parasite. Notably, T. gondii antibodies were found in 83.3%
      (15/18) of the Rufous-bellied Thrush (Turdus rufiventris). 

PMID- 24332962
TI  - Further studies on the necessity or otherwise of multiple pre-treatment groups in
      faecal egg count reduction tests in sheep.
AB  - Data utilised in a previous study to compare two different faecal egg count
      reduction tests (FECRTs) in sheep involving multiple anthelmintic treatments and
      undifferentiated faecal egg counts (FECs), were re-examined using FECs for
      individual parasite genera. The first of these FECRTs was based on changes in the
      pre- and post-treatment FECs of the same groups of animals. The other represented
      an abbreviated version of the former procedure and involved only a single common
      pre-treatment group as a baseline for comparing all post-treatment results. A
      comparison of the results obtained with these two procedures showed that the use
      of either one of them was likely to provide similar estimates of anthelmintic
      efficacy and the detection of a comparable number of cases of anthelmintic
      resistance for all parasite genera. These findings offer further support to a
      previously expressed view that the use of the more complex and costly pre- and
      post-treatment FECRT procedure is unlikely to provide any real advantages over
      the simpler one. 

PMID- 24332963
TI  - Longitudinal prevalence, oocyst shedding and molecular characterisation of
      Cryptosporidium species in sheep across four states in Australia.
AB  - The prevalence of Cryptosporidium in sheep in the eastern states of Australia has
      not been well described, therefore a study of the prevalence, oocyst
      concentration, species and subtypes of Cryptosporidium were assessed from lamb
      faecal samples at three sampling periods (weaning, post-weaning and pre
      slaughter) from eight farms across South Australia, New South Wales, Victoria and
      Western Australia. A total of 3412 faecal samples were collected from
      approximately 1182 lambs across the four states and screened for the presence of
      Cryptosporidium using a quantitative PCR (qPCR) at the actin locus. Positives
      were typed at the 18S locus and at a second locus using C. parvum and C. hominis
      specific qPCR primers. The overall prevalence was 16.9% (95% CI: 15.6-18.1%) and
      of the 576 positives, 500 were successfully genotyped. In general, the prevalence
      of Cryptosporidium was higher in WA than the eastern states. Cryptosporidium
      prevalence peaked at 43.9% and 37.1% at Pingelly (WA2) and Arthur River (WA1),
      respectively during weaning and at Pingelly (WA2) during pre-slaughter (36.4%).
      The range of oocyst shedding at weaning overall across all states was 63
      7.9*10(6) and the median was 3.2 * 10(4) oocysts g(-1). The following species
      were identified; C. xiaoi (69%-345/500), C. ubiquitum (17.6%-88/500), C. parvum
      (9.8%-49/500), C. scrofarum (0.8%-4/500), mixed C. parvum and C. xiaoi (2.4%
      12/500), C. andersoni (0.2%-1/500) and sheep genotype 1 (0.2%-1/500). Subtyping
      of C. parvum and C. ubiquitum isolates identified IIa and IId subtype families
      within C. parvum (with IId as the dominant subtype) and XIIa within C. ubiquitum.
      This is the first published description of C. parvum subtypes detected in lambs
      in Australia.

PMID- 24332964
TI  - In vitro and in vivo effects of neem tree (Azadirachta indica A. Juss) products
      on larvae of the sheep nose bot fly (Oestrus ovis L. Diptera: Oestridae).
AB  - Two studies were carried out in order to test the effects of neem tree extracts
      (Azadirachta indica A. Juss) on sheep bot fly larvae (Oestrus ovis L. Diptera:
      Oestridae). First, aqueous extracts from neem seeds (ASNE) at 0, 5 y 10% (w/v)
      concentrations were tested on larval mortality in vitro. In a second study, the
      effect of oral administration with neem seed meal (0, 100 y 200mg/kg) and neem
      leaves (1% of diet) on number of larvae found at necropsy and larval development
      was evaluated in experimentally O. ovis-infected sheep. Results in Experiment 1
      showed a significant (P<0.05) effect of ASNE on time to L1 mortality in a dosis
      dependent manner. In Experiment 2, oral administration of seeds or leaves did not
      affect the number of larvae found at necropsy of the sheep, but interfered with
      larval development and there was a tendency to reduce larval weight at the end of
      the infection period (55d).

PMID- 24332965
TI  - A path analysis of Internet health information seeking behaviors among older
      adults.
AB  - The Internet has emerged as an innovative tool that older adults can use to
      obtain health-related information. However, the relationships among predictors of
      Internet health information seeking behaviors (IHISB) in this population are not
      well understood. To fill this gap, this study examined the direct and indirect
      pathways of potential predictors of IHISB among older South Korean adults, using
      the modified Technology Acceptance Model 3. Participants were 300 older South
      Korean adults who had used the Internet to obtain health information within the
      past month. Data were collected via a self-report questionnaire and were analyzed
      through structural equation modeling. Two variables-prior experience and
      behavioral intention to use-had positive direct effects on IHISB. These findings
      imply that health care providers promoting IHISB among older adults should
      consider these individuals' prior experience with the Internet and their
      willingness to use the Internet as a source of health information. 

PMID- 24332966
TI  - A 22-year-old woman with rash and dysphagia.

PMID- 24332967
TI  - Partial and transient reduction of glycolysis by PFKFB3 blockade reduces
      pathological angiogenesis.
AB  - Strategies targeting pathological angiogenesis have focused primarily on blocking
      vascular endothelial growth factor (VEGF), but resistance and insufficient
      efficacy limit their success, mandating alternative antiangiogenic strategies. We
      recently provided genetic evidence that the glycolytic activator
      phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) promotes vessel
      formation but did not explore the antiangiogenic therapeutic potential of PFKFB3
      blockade. Here, we show that blockade of PFKFB3 by the small molecule 3-(3
      pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) reduced vessel sprouting in
      endothelial cell (EC) spheroids, zebrafish embryos, and the postnatal mouse
      retina by inhibiting EC proliferation and migration. 3PO also suppressed vascular
      hyperbranching induced by inhibition of Notch or VEGF receptor 1 (VEGFR1) and
      amplified the antiangiogenic effect of VEGF blockade. Although 3PO reduced
      glycolysis only partially and transiently in vivo, this sufficed to decrease
      pathological neovascularization in ocular and inflammatory models. These insights
      may offer therapeutic antiangiogenic opportunities.

PMID- 24332969
TI  - Cost burden of 30-day readmissions following Medicare total hip and knee
      arthroplasty.
AB  - The Centers for Medicare and Medicaid Services has proposed bundling of payments
      for acute care episodes for certain procedures, including total joint
      arthroplasty. The purpose of this study is to quantify the readmission burden of
      TJA as a function of readmission rate and reimbursement for the bundled payment.
      Using the hospital's administrative database, we identified all unplanned 30-day
      readmissions following index admissions for total hip and total knee
      arthroplasty, and revision hip and knee arthroplasty among Medicare beneficiaries
      from 2009 to 2012. For each group, we determined 30-day readmission rates and
      direct costs of each readmission. The hospital cost margins for Medicare TJAs are
      small and any decrease in these margins can potentially make performing these
      procedures economically unfeasible potentially decreasing Medicare patient
      access. 

PMID- 24332968
TI  - Type 2 diabetes and congenital hyperinsulinism cause DNA double-strand breaks and
      p53 activity in beta cells.
AB  - beta cell failure in type 2 diabetes (T2D) is associated with hyperglycemia, but
      the mechanisms are not fully understood. Congenital hyperinsulinism caused by
      glucokinase mutations (GCK-CHI) is associated with beta cell replication and
      apoptosis. Here, we show that genetic activation of beta cell glucokinase,
      initially triggering replication, causes apoptosis associated with DNA double
      strand breaks and activation of the tumor suppressor p53. ATP-sensitive potassium
      channels (KATP channels) and calcineurin mediate this toxic effect. Toxicity of
      long-term glucokinase overactivity was confirmed by finding late-onset diabetes
      in older members of a GCK-CHI family. Glucagon-like peptide-1 (GLP-1) mimetic
      treatment or p53 deletion rescues beta cells from glucokinase-induced death, but
      only GLP-1 analog rescues beta cell function. DNA damage and p53 activity in T2D
      suggest shared mechanisms of beta cell failure in hyperglycemia and CHI. Our
      results reveal membrane depolarization via KATP channels, calcineurin signaling,
      DNA breaks, and p53 as determinants of beta cell glucotoxicity and suggest
      pharmacological approaches to enhance beta cell survival in diabetes.

PMID- 24332970
TI  - One-stage revision arthroplasty using cementless stem for infected hip
      arthroplasties.
AB  - The objective of this retrospective study was to evaluate our results with one
      stage revision using cementless femoral stem for infected hip arthroplasties.
      Twenty-four patients were included in the study. The acetabular component was
      cemented in 9 cases. In 2 patients a structured bone allograft was necessary to
      fill an acetabular defect. After a mean follow-up of 44.6 months, 23 patients
      showed no signs of infection (95.8%), the mean functional response according to
      the Merle d'Aubigne scale was 13.8 and the mean Harris Hip Score was 65.4. One
      stage revision hip arthroplasty using cementless femoral stem was associated with
      a high success rate.

PMID- 24332971
TI  - Safe havens and rough waters: networks, place, and the navigation of risk among
      injection drug-using Malaysian fishermen.
AB  - BACKGROUND: HIV prevalence among Malaysian fishermen is ten times that of the
      general population. Fishing boats are a key place where drug use occurs, but we
      know little about how these environments shape HIV risk behaviour. Utilizing
      Rhodes' 'risk environment' framework, we assessed drug use contexts and how
      characteristics of place associated with fishing and fishermen's social networks
      served as key axes along which drug use and HIV risk behaviour occurred. METHODS:
      Data were collected during 2009-2011 in Kuantan, a fishing port on the eastern
      coast of Malaysia, and include 28 in-depth interviews and 398 surveys collected
      using RDS. Logistic regression was used to determine the effect of occupational,
      network and risk environment characteristics on unsafe injection behaviour and
      access to clean needles/syringes; qualitative data were coded and analyzed
      thematically. RESULTS: Drug injecting was common and occurred on boats, often
      with other crewmembers. Captains and crewmembers were aware of drug use. Unsafe
      injection practices were significantly associated with having a larger proportion
      of drug injectors in network (OR=3.510, 95% CI=1.053-11.700) and having a captain
      provide drugs for work (OR=2.777, 95% CI=1.018-7.576). Size of fishermen network
      (OR=0.987, 95% CI=0.977-0.996), crewmembers' knowledge of drug use (OR=7.234, 95%
      CI=1.430-36.604), and having a captain provide drugs for work (OR=0.134, 95%
      CI=0.025-0.720) predicted access to clean needles/syringes. Qualitative analyses
      revealed that occupational culture and social relationships on boats drove drug
      use and HIV risk. CONCLUSIONS: While marginalized in broader society, the
      acceptance of drug use within the fishing community created occupational networks
      of risk. Fishing boats were spaces of both risk and safety; where drug users
      participated in the formal economy, but also where HIV risk behaviour occurred.
      Understanding the interplay between social networks and place is essential for
      developing HIV prevention and harm reduction policies appropriate for the unique
      needs of this fishing population.

PMID- 24332972
TI  - Negotiating place and gendered violence in Canada's largest open drug scene.
AB  - BACKGROUND: Vancouver's Downtown Eastside is home to Canada's largest street
      based drug scene and only supervised injection facility (Insite). High levels of
      violence among men and women have been documented in this neighbourhood. This
      study was undertaken to explore the role of violence in shaping the socio-spatial
      relations of women and 'marginal men' (i.e., those occupying subordinate
      positions within the drug scene) in the Downtown Eastside, including access to
      Insite. METHODS: Semi-structured qualitative interviews were conducted with 23
      people who inject drugs (PWID) recruited through the Vancouver Area Network of
      Drug Users, a local drug user organization. Interviews included a mapping
      exercise. Interview transcripts and maps were analyzed thematically, with an
      emphasis on how gendered violence shaped participants' spatial practices.
      RESULTS: Hegemonic forms of masculinity operating within the Downtown Eastside
      framed the everyday violence experienced by women and marginal men. This violence
      shaped the spatial practices of women and marginal men, in that they avoided drug
      scene milieus where they had experienced violence or that they perceived to be
      dangerous. Some men linked their spatial restrictions to the perceived 'dope
      quality' of neighbourhood drug dealers to maintain claims to dominant
      masculinities while enacting spatial strategies to promote safety. Environmental
      supports provided by health and social care agencies were critical in enabling
      women and marginal men to negotiate place and survival within the context of drug
      scene violence. Access to Insite did not motivate participants to enter into
      "dangerous" drug scene milieus but they did venture into these areas if necessary
      to obtain drugs or generate income. CONCLUSION: Gendered violence is critical in
      restricting the geographies of men and marginal men within the street-based drug
      scene. There is a need to scale up existing environmental interventions,
      including supervised injection services, to minimize violence and potential drug
      related risks among these highly-vulnerable PWID.

PMID- 24332973
TI  - A case of cervical juxtafacet cyst with extensive rim enhancement on Gd-DTPA MRI.
AB  - The authors reported a case of cervical juxtafacet cyst with extensive rim
      enhancement on gadolinium-diethylenetriamine pentaacid magnetic resonance
      imaging. Operative finding revealed the epidural space around the mass filled
      with abundant venous plexus. Histological examination demonstrated that cyst wall
      was composed of the well-vascularized fibrous connective tissue with some
      inflammatory changes. We speculate that extensive rim enhancement of juxtafacet
      cyst may be attributed not only to the chronic inflammatory changes of cyst wall,
      but to engorged venous plexus within the widened epidural space. 

PMID- 24332974
TI  - Clinical application of 3D VIBECAIPI-DIXON for non-enhanced imaging of the
      pancreas compared to a standard 2D fat-saturated FLASH.
AB  - PURPOSE: To compare a fast 3D VIBE sequence with Dixon fat saturation and
      CAIPIRINHA acceleration techniques (3D VIBE(CAIPI-DIXON)) to a standard 2D FLASH
      sequence with spectral fat saturation and conventional GRAPPA acceleration
      technique (2D Flash(GRAPPA-fs)) for non-enhanced imaging of the pancreas. METHODS
      AND MATERIALS: In this retrospective, institutional review board-approved intra
      individual comparison study, 29 patients (7 female, 22 male; mean age 60.4 +/-
      20.9 years) examined on a 48-channel 3.0-T MR system (MAGNETOM Skyra VD 13,
      Siemens Healthcare Sector, Germany) were included. 3D VIBE(CAIPI-DIXON) (TR/TE
      3.95/2.5+1.27 ms; spatial resolution-1.2 * 1.2 * 3.0 mm(3); CAIPIRINHA 2 * 2 [1],
      acquisition time-0:12 min) and 2D Flash(GRAPPA-fs) (TR/TE-195/3.69 ms; 1.2 * 1.2
      * 3.0 mm(3); GRAPPA 2, 3 * 0:21 min) sequences were performed in each subject in
      random order prior to the administration of an intravenous contrast agent. Two
      radiologists evaluated the images with regard to diagnostic preference. Semi
      quantitative signal ratios were calculated for the pancreas versus the liver,
      spleen, muscle, and visceral fat. Inter-reader agreement was calculated using
      unweighted Cohen's kappa. Signal ratio results were analyzed using a univariate
      analysis of variance. Additional signal-to-noise (SNR) measurements were
      performed in a phantom. RESULTS: 3D VIBE(CAIPI-DIXON) was preferred in 72.4%
      (both readers) and 2D Flash(GRAPPA-fs) in 3.4%/6.9% (reader 1/2) of cases with a
      kappa value of 0.756. The main reasons for this preference were homogenous fat
      saturation with 3D VIBE(CAIPI-DIXON) and reduced motion artifacts due to a faster
      acquisition, leading to improved delineation of the pancreas. Signal ratios of
      pancreatic to fat signal for 3D VIBE(CAIPI-DIXON) (10.08 +/- 3.48) and 2D
      Flash(GRAPPA-fs) (6.53 +/- 3.07) were statistically different (P<.001). However,
      no additional statistically significant differences in signal ratios were
      identified (range: 0.73 +/- 0.18 to 1.37 +/- 0.40; .514<P<.961). SNR did not
      statistically significantly differ between the sequences. CONCLUSION: 3D
      VIBE(CAIPI-DIXON) enables robust pancreatic imaging with a shorter time and
      improved fat suppression relative to conventional 2D Flash(GRAPPA-fs). At an
      acquisition time of 12 seconds, 3D VIBE(CAIPI-DIXON) can be obtained in
      considerably less time than standard fat-saturated VIBE sequences.

PMID- 24332975
TI  - 68Ga-DOTATOC PET-CT in the localization of source of ectopic ACTH in patients
      with ectopic ACTH-dependent Cushing's syndrome.
AB  - Localization of the source of adrenocorticotrophic hormone (ACTH) in ectopic ACTH
      induced Cushing's syndrome is of paramount importance as definitive management
      mainly involves surgical resection of tumor. Many of these are occult, not
      identified by conventional structural imaging. Accurate localization and
      assessment of their functional status has become feasible with the use positron
      emission tomography-computerized tomography using (68)Ga-DOTATOC (1,4,7,10
      tetraazacy-clododecane-NI,NII,NIII,NIIII-tetraacetic acid(D)-Phe1-thy3
      octreotide), aiding in proper planning for their definitive management. 

PMID- 24332976
TI  - Computed tomography (CT) of fractures of the ankle and foot: correlating fracture
      patterns with the presence of tenosynovial fat: Tenosynovial fat in ankle and
      foot fractures.
AB  - PURPOSE: To correlate ankle and foot fracture patterns with the presence of
      tenosynovial fat on computed tomography (CT). MATERIALS AND METHODS: In this
      retrospective, cross-sectional, observation study, two blinded musculoskeletal
      radiologists independently reviewed 89 CT scans of patients with ankle or foot
      fractures and recorded the presence of fat about Henry's knot, tibialis posterior
      tendon, and peroneus longus tendon. RESULTS: The agreement between the two
      readers ranged from excellent to substantial. Sixteen to 23 percent of fractures
      were associated with tenosynovial fat. CONCLUSIONS: The finding of tenosynovial
      fat following ankle or foot trauma warrants a closer search for a fracture.

PMID- 24332977
TI  - Best estimation of spectrum profiles for diagnosing femoral prostheses loosening.
AB  - For the past few years, some authors have proposed several vibration analysis
      techniques to detect the prosthetic femoral stem loosening, having found some
      differences in the frequency response between secure and loose stems. Classical
      methods like periodogram have been used in most studies for the spectral
      estimation, and their conclusions have been reached only by visual inspection. A
      new metric called Non-linear Logarithmic Weighted Distance (NLWD), based on log
      spectral distance is presented. As its name suggests, the spectral power is
      weighted in order to highlight discriminatory patterns of the spectral profiles.
      A Generalized Discriminant Ratio (GDR) based on NLWD metric has been also
      defined. In this study, experiments on a cadaveric dried bone with two kinds of
      fixation, Loose Stem class (LS) and Secure Stem class (SS), have been analyzed.
      To select the most discriminating approach to spectral estimation, five well
      known algorithms (Welch's, Burg's Auto-Regressive (AR), Auto-Regressive Moving
      Average (ARMA), Multiple Signal Classification (MUSIC) and Thomson's Multi-taper
      (MTM)) have been compared by using GDR. Finally, the use of the MTM method is
      proposed for the analysis of bone-stem interface vibratory signals, since it
      yields the most discriminatory profiles. 

PMID- 24332979
TI  - Structure-function relationship and evolutionary history of the human
      selenoprotein M (SelM) found over-expressed in hepatocellular carcinoma.
AB  - In humans we know 25 selenoproteins that play important roles in redox
      regulation, detoxification, immune-system protection and viral suppression. In
      particular, selenoprotein M (SelM) may function as thiol disulfide oxidoreductase
      that participates in the formation of disulfide bonds, and can be implicated in
      calcium responses. However, it presents a redox motif (CXXU), where U is a
      selenocysteine, and may also function as redox regulator because its decreased or
      increased expression regulated by dietary selenium alters redox homeostasis. No
      data are reported in literature about its involvement in cancer but only in
      neurodegenerative diseases. In this paper we evaluated the SelM expression in two
      hepatoma cell lines, HepG2 and Huh7, compared to normal hepatocytes. The results
      suggested its involvement in hepatocellular carcinoma (HCC) as well as its
      possible use to follow the progression of this cancer as putative marker. The aim
      of this study has been to analyze the structure-function relationships of SelM.
      Hence, firstly we studied the evolutionary history of this protein by
      phylogenetic analysis and GC content of genes from various species. So, we
      modeled the three-dimensional structure of the human SelM evaluating its
      energetic stability by molecular dynamics simulations. Moreover, we modeled some
      of its mutants to obtain structural information helpful for structure-based drug
      design. 

PMID- 24332978
TI  - A view to a kill: the bacterial type VI secretion system.
AB  - The bacterial type VI secretion system (T6SS) is an organelle that is
      structurally and mechanistically analogous to an intracellular membrane-attached
      contractile phage tail. Recent studies determined that a rapid conformational
      change in the structure of a sheath protein complex propels T6SS spike and tube
      components along with antibacterial and antieukaryotic effectors out of predatory
      T6SS(+) cells and into prey cells. The contracted organelle is then recycled in
      an ATP-dependent process. T6SS is regulated at transcriptional and
      posttranslational levels, the latter involving detection of membrane perturbation
      in some species. In addition to directly targeting eukaryotic cells, the T6SS can
      also target other bacteria coinfecting a mammalian host, highlighting the
      importance of the T6SS not only for bacterial survival in environmental
      ecosystems, but also in the context of infection and disease. This review
      highlights these and other advances in our understanding of the structure,
      mechanical function, assembly, and regulation of the T6SS. 

PMID- 24332980
TI  - Validation of the reliability of computational O-GlcNAc prediction.
AB  - O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational
      modification, which regulates numerous cellular processes such as gene
      expression, translation, immune reactions, protein degradation, protein-protein
      interaction, apoptosis, and signal transduction. In contrast to N-linked
      glycosylation, O-GlcNAcylation does not display a strict amino acid consensus
      sequence, although serine or threonine residues flanked by proline and valine are
      preferred sites of O-GlcNAcylation. Based on this information, computational
      prediction tools of O-GlcNAc sites have been developed. Here, we retrospectively
      assessed the performance of two available O-GlcNAc prediction programs YinOYang
      1.2 server and OGlcNAcScan by comparing their predictions for recently discovered
      experimentally validated O-GlcNAc sites. Both prediction programs efficiently
      identified O-GlcNAc sites situated in an environment resembling the consensus
      sequence P-P-V-[ST]-T-A. However, both prediction programs revealed numerous
      false negative O-GlcNAc predictions when the site of modification was located in
      an amino acid sequence differing from the known consensus sequence. By searching
      for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic
      proteins preferably occurs at serine and threonine residues flanked downstream by
      proline and valine and upstream by one to two alanines followed by a stretch of
      serine and threonine residues. However, O-GlcNAcylation of proteins located in
      the mitochondria or in the secretory lumen occurs at different sites and does not
      follow a distinct consensus sequence. Thus, our study indicates the limitations
      of the presently available computational prediction methods for O-GlcNAc sites
      and suggests that experimental validation is mandatory. Continuously update and
      further development of available databases will be the key to improve the
      performance of O-GlcNAc site prediction. 

PMID- 24332982
TI  - The dementia cognitive fluctuation scale, a new psychometric test for clinicians
      to identify cognitive fluctuations in people with dementia.
AB  - OBJECTIVES: Cognitive fluctuation (CF) is a common feature of dementia and a core
      diagnostic symptom for dementia with Lewy bodies (DLB). CF remains difficult to
      accurately and reliably detect clinically. This study aimed to develop a
      psychometric test that could be used by clinicians to facilitate the
      identification of CF and improve the recognition and diagnosis of DLB and
      Parkinson disease, and to improve differential diagnosis of other dementias.
      METHODS: We compiled a 17-item psychometric test for identifying CF and applied
      this measure in a cross-sectional design. Participants were recruited from the
      North East of England, and assessments were made in individuals' homes. We
      recruited people with four subtypes of dementia and a healthy comparison group,
      and all subjects were administered this pilot scale together with other standard
      ratings. The psychometric properties of the scale were examined with exploratory
      factor analysis. We also examined the ability of individual items to identify CF
      to discriminate between dementia subtypes. The sensitivity and specificity of
      discriminating items were explored along with validity and reliability analyses.
      RESULTS: Participants comprised 32 comparison subjects, 30 people with Alzheimer
      disease, 30 with vascular dementia, 29 with DLB, and 32 with dementia associated
      with Parkinson disease. Four items significantly discriminated between dementia
      groups and showed good levels of sensitivity (range: 78.6%-80.3%) and specificity
      (range: 73.9%-79.3%). The scale had very good levels of test-retest (Cronbach's
      alpha: 0.82) and interrater (0.81) reliabilities. The four items loaded onto
      three different factors. These items were: 1) marked differences in functioning
      during the daytime; 2) daytime somnolence; 3) daytime drowsiness; and 4) altered
      levels of consciousness during the day. CONCLUSIONS: We identified four items
      that provide valid, sensitive, and specific questions for reliably identifying CF
      and distinguishing the Lewy body dementias from other major causes of dementia
      (Alzheimer disease and vascular dementia).

PMID- 24332981
TI  - Alpha-2 Heremans Schmid Glycoprotein (AHSG) modulates signaling pathways in head
      and neck squamous cell carcinoma cell line SQ20B.
AB  - This study was performed to identify the potential role of Alpha-2 Heremans
      Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC)
      tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among
      cancer cell lines, in that they produce endogenous AHSG and do not rely, solely,
      on AHSG derived from serum. To produce our model, we performed a stable
      transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in
      three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG
      production and EV which is the empty vector control expressing wild-type levels
      of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on
      cellular adhesion, proliferation, migration and invasion in a serum-free
      environment. We demonstrated that sublines EV and AH50 adhered to plastic and
      laminin significantly faster than the AH20 cell line, supporting the previously
      reported role of exogenous AHSG in cell adhesion. As for proliferative potential,
      EV had the greatest amount of proliferation with AH50 proliferation significantly
      diminished. AH20 cells did not proliferate at all. Depletion of AHSG also
      diminished cellular migration and invasion. TGF-beta was examined to determine
      whether levels of the TGF-beta binding AHSG influenced the effect of TGF-beta on
      cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-beta
      influenced SMAD and ERK signaling, it did not clearly affect proliferation,
      suggesting that AHSG influences on adhesion, proliferation, invasion and
      migration are primarily due to its role in adhesion and cell spreading. The
      previously reported role of AHSG in potentiating metastasis via protecting MMP-9
      from autolysis was also supported in this cell line based model system of
      endogenous AHSG production in HNSCC. Together, these data show that endogenously
      produced AHSG in an HNSCC cell line, promotes in vitro cellular properties
      identified as having a role in tumorigenesis. 

PMID- 24332983
TI  - Increased nuchal translucency with normal karyotype and anomaly scan: what next?
AB  - Over the years, it has become clear that increased nuchal translucency is a
      marker for chromosomal abnormalities, and it is also associated with a wide
      spectrum of structural anomalies, genetic syndromes, a higher risk of
      miscarriage, and intrauterine fetal death. These risks are all proportionally
      related to the degree of nuchal translucency enlargement. After the initial
      assessment of increased nuchal translucency, parents should be counselled by the
      fetal medicine specialist about the possible outcomes and the value of additional
      karyotyping and array comparative genomic hybridisation. A detailed late first
      trimester and subsequent 20-week scan should aim at identifying structural
      anomalies, with special focus on the fetal heart and subtle dysmorphic features.
      In the absence of structural anomalies or markers, the chance of a favourable
      outcome is high. 

PMID- 24332985
TI  - Blood markers of fatty acids and vitamin D, cardiovascular measures, body mass
      index, and physical activity relate to longitudinal cortical thinning in normal
      aging.
AB  - We hypothesized that higher levels of omega-3 fatty acids, vitamin D, and
      physical activity relate to cortical sparing, whereas higher levels of
      cholesterol, systolic blood pressure, and body mass index (BMI) relate to
      increased atrophy in the adult lifespan. Longitudinal measures of cortical
      thickness were derived from magnetic resonance imaging scans acquired (mean
      interval 3.6 years) from 203 healthy persons aged 23-87 years. At follow-up,
      measures of BMI, blood pressure, and physical activity were obtained. Blood
      levels of docosahexaenoic acid, eicosapentaenoic acid, vitamin D, and cholesterol
      were measured in a subsample (n = 92). Effects were tested in cortical surface
      based analyses, with sex, age, follow-up interval, and the interactions between
      each included as covariates. Higher levels of docosahexaenoic acid, vitamin D,
      and physical activity related to cortical sparing. Higher cholesterol and BMI
      related to increased cortical thinning. Effects were independent, did not
      interact with age, and the cholesterol effect was restricted to males.
      Eicosapentaenoic acid and blood pressure showed no effects. The observed effects
      show promise for potential factors to reduce cortical atrophy in normal aging. 

PMID- 24332984
TI  - Genetic targeting of the amphetamine and methylphenidate-sensitive dopamine
      transporter: on the path to an animal model of attention-deficit hyperactivity
      disorder.
AB  - Alterations in dopamine (DA) signaling underlie the most widely held theories of
      molecular and circuit level perturbations that lead to risk for attention-deficit
      hyperactivity disorder (ADHD). The DA transporter (DAT), a presynaptic reuptake
      protein whose activity provides critical support for DA signaling by limiting DA
      action at pre- and postsynaptic receptors, has been consistently associated with
      ADHD through pharmacological, behavioral, brain imaging and genetic studies.
      Currently, the animal models of ADHD exhibit significant limitations, stemming in
      large part from their lack of construct validity. To remedy this situation, we
      have pursued the creation of a mouse model derived from a functional
      nonsynonymous variant in the DAT gene (SLC6A3) of ADHD probands. We trace our
      path from the identification of these variants to in vitro biochemical and
      physiological studies to the production of the DAT Val559 mouse model. We discuss
      our initial findings with these animals and their promise in the context of
      existing rodent models of ADHD. 

PMID- 24332986
TI  - Modulation of lipopolysaccharide-induced memory insult, gamma-secretase, and
      neuroinflammation in triple transgenic mice by 5-lipoxygenase.
AB  - Besides amyloid and tau pathology, a constant feature of Alzheimer's disease (AD)
      is an intense inflammatory response, which is considered an active player in its
      pathogenesis. The 5-Lipoxygenase (5LO) is a proinflammatory enzyme and an
      endogenous modulator of AD-like phenotype in mouse models of the disease. To
      further understand the role of 5LO in AD pathogenesis, we exposed the triple
      transgenic (3*Tg) and 3*Tg/5LO knockout mice to lipopolysaccharide (LPS), a known
      inducer of neuroinflammation, and evaluated its effect on their AD-like
      phenotype. 3*Tg mice treated with LPS manifested a worsening of behavior, gamma
      secretase up-regulation, and increased neuroinflammatory responses. These effects
      were completely prevented in 3*Tg mice genetically deficient for 5LO. By
      contrast, the absence of 5LO did not protect against increase in tau
      phosphorylation at specific epitopes that were mediated by the activation of the
      cyclin-dependent kinase 5. Our data demonstrate that the 5LO pathway affects key
      neuropathological features of the AD-like phenotype (behavior, abeta,
      microgliosis, astrocytosis) but not others (tau pathology) in the LPS-dependent
      neuroinflammation model. The opposite ways whereby 5LO influences the LPS
      dependent effects in vivo supports the complex nature of the neuroinflammatory
      response in AD and its differential role in modulating amyloid and tau
      neuropathology. 

PMID- 24332988
TI  - A continuous, real-time water quality monitoring system for the coral reef
      ecosystems of Nanwan Bay, Southern Taiwan.
AB  - The coral reef ecosystems of Nanwan Bay, Southern Taiwan are undergoing
      degradation due to anthropogenic impacts, and as such have resulted in a decline
      in coral cover. As a first step in preventing the continual degradation of these
      coral reef environments, it is important to understand how changes in water
      quality affect these ecosystems on a fine-tuned timescale. To this end, a real
      time water quality monitoring system was implemented in Nanwan Bay in 2010. We
      found that natural events, such as cold water intrusion due to upwelling, tended
      to elicit temporal shifts in coral spawning between 2010 and 2011. In addition,
      Degree Heating Weeks (DHWs), a commonly utilized predictor of coral bleaching,
      were 0.92 and 0.59 in summer 2010 and 2011, respectively. Though this quantity of
      DHW was below the presumed stress-inducing value for these reefs, a rise in DHWs
      in the future may stress the resident corals. 

PMID- 24332987
TI  - Dopamine and glutamate receptor genes interactively influence episodic memory in
      old age.
AB  - Both the dopaminergic and glutamatergic systems modulate episodic memory
      consolidation. Evidence from animal studies suggests that these two
      neurotransmitters may interact in influencing memory performance. Given that
      individual differences in episodic memory are heritable, we investigated whether
      variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D
      aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the
      glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively
      modulate episodic memory in large samples of younger (20-31 years; n = 670) and
      older (59-71 years; n = 832) adults. We found a reliable gene-gene interaction,
      which was observed in older adults only: older individuals carrying genotypes
      associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed
      better episodic performance. These results are in line with findings showing
      magnification of genetic effects on memory in old age, presumably as a
      consequence of reduced brain resources. Our findings underscore the need for
      investigating interactive effects of multiple genes to understand individual
      difference in episodic memory.

PMID- 24332989
TI  - Stabilization of dentin matrix after cross-linking treatments, in vitro.
AB  - OBJECTIVES: To evaluate the effect of EDC on elastic modulus (E), MMPs activity,
      hydroxyproline (HYP) release and thermal denaturation temperature of
      demineralized dentin collagen. METHODS: Dentin beams were obtained from human
      molars and completely demineralized in 10 wt% H3PO4 for 18 h. The initial E and
      MMP activity were determined with three-point bending and microcolorimetric
      assay, respectively. Extra demineralized beams were dehydrated and the initial
      dry mass (DM) was determined. All the beams were distributed into groups (n=10)
      and treated for 30 s or 60 s with: water, 0.5 M, 1 M or 2 M EDC or 10%
      glutaraldehyde (GA). After treatment, the new E and MMP activity were
      redetermined. The beams submitted to DM measurements were storage for 1 week in
      artificial saliva, after that the mass loss and HYP release were evaluated. The
      collagen thermal denaturation temperature (TDT) was determined by DSC analysis.
      Data for E, MMP activity and HYP release were submitted to Wilcoxon and Kruskal
      Wallis or Mann-Whitney tests. Mass loss and TDT data were submitted to ANOVA and
      Tukey tests at the 5% of significance. RESULTS: EDC was able to significantly
      increase collagen stiffness in 60s. 10% GA groups obtained the highest E values
      after both 30 and 60s. All cross-linking agents decreased MMP activity and HYP
      release and increased TDT temperature. Significant differences were identified
      among EDC groups after 30 or 60 s of cross-linking, 1M or 2M EDC showed the
      lowest MMP activity. SIGNIFICANCE: Cross-linking agents are capable of preventing
      dentin collagen degradation. EDC treatment may be clinically useful to increase
      resin-dentin stability.

PMID- 24332990
TI  - Indocyanine green clearance as an outcome prediction tool in cardiac surgery: a
      prospective study.
AB  - PURPOSE: To evaluate the role of plasma disappearance rate of indocyanine green
      (PDR-ICG) as an outcome prediction tool in cardiac surgery. PATIENTS AND METHODS:
      One hundred ninety patients undergoing coronary artery bypass grafting, valve
      surgery or combined procedures were enrolled. PDR-ICG measurements along with
      standard lab values were performed preoperative and on postoperative days 1, 2,
      and on discharge from the intensive care unit. Adverse outcomes were defined as
      prolonged length of stay in the intensive care unit and/or mortality. Two groups
      were defined according to length of stay in the intensive care unit (<= 3 days vs
      >3 days). RESULTS: PDR-ICG values differed significantly for all time points
      between the groups. In a multivariate model, in patients over 65 years with a
      EuroSCORE below 8.5, a preoperative PDR-ICG value below 12.85%/min was the
      strongest independent predictor for prolonged intensive care unit stay (>3 days).
      A preoperative PDR-ICG value below 8.2%/min was the strongest independent
      predictor for mortality in a multivariate analysis including age, cardiac
      function, and EuroSCORE. CONCLUSIONS: In addition to the established scores, PDR
      ICG may provide valuable information for the assessment of perioperative
      morbidity and mortality in cardiac surgery. Pre- and early postoperative
      measurements may help to identify patients at risk for developing perioperative
      complications.

PMID- 24332991
TI  - High-frequency percussive ventilation improves oxygenation and ventilation in
      pediatric patients with acute respiratory failure.
AB  - PURPOSE: High-frequency percussive ventilation (HFPV) in pediatrics has been
      described predominantly in burned patients. We aimed to describe its
      effectiveness and safety in noninhalational pediatric acute respiratory failure
      (ARF). METHODS: We conducted an observational study in a tertiary care pediatric
      intensive care unit on 31 patients with ARF failing conventional ventilation
      transitioned to HFPV. Demographics, ventilator settings, oxygenation index,
      oxygen saturation index, oxygen saturation as measured by pulse oximetry/fraction
      of inspired oxygen (Fio2), and Pao2/Fio2 were recorded before and during HFPV.
      RESULTS: Initiation of HFPV was associated with improvements in oxygenation
      index, oxygen saturation index, Pao2/Fio2, and oxygen saturation as measured by
      pulse oximetry/Fio2 as early as 12 hours (P < .05), which continued through 48
      hours after transition. Improved oxygenation occurred without an increase in mean
      airway pressures. Reductions in Paco2 occurred 6 hours after initiation of HFPV
      and continued through 48 hours (P < .01). Improved gas exchange was accompanied
      by reduced peak-inflating pressures at all time intervals after initiation of
      HPFV (P < .01). Vasopressor scores were similar before and after initiation of
      HFPV in patients requiring vasoactive support. Twenty-six (83.9%) of 31 patients
      survived to hospital discharge. CONCLUSIONS: In a heterogeneous population of
      pediatric ARF failing conventional ventilation, HFPV efficiently improves gas
      exchange in a lung-protective manner.

PMID- 24332992
TI  - Hypoglycemia is associated with increased mortality in patients with acute
      decompensated liver cirrhosis.
AB  - PRINCIPALS: The liver plays an important role in glucose metabolism, in terms of
      glucolysis and gluconeogenesis. Several studies have shown that hyperglycemia in
      patients with liver cirrhosis is associated with progression of the liver disease
      and increased mortality. However, no study has ever targeted the influence of
      hypoglycemia. The aim of this study was to assess the association of glucose
      disturbances with outcome in patients presenting to the emergency department with
      acute decompensated liver cirrhosis. METHODS: Our retrospective data analysis
      comprised adult (>= 16 years) patients admitted to our emergency department
      between January 1, 2002, and December 31, 2012, with the primary diagnosis of
      decompensated liver cirrhosis. RESULTS: A total of 312 patients were eligible for
      study inclusion. Two hundred thirty-one (74.0%) patients were male; 81 (26.0%)
      were female. The median age was 57 years (range, 51-65 years). Overall, 89
      (28.5%) of our patients had acute glucose disturbances; 49 (15.7%) of our
      patients were hypoglycemic and 40 (12.8%) were hyperglycemic. Patients with
      hypoglycemia were significantly more often admitted to the intensive care unit
      than hyperglycemic patients (20.4% vs 10.8%, P < .015) or than normoglycemic
      patients (20.4% vs 10.3%, P < .011), and they significantly more often died in
      the hospital (28.6% hypoglycemic vs 7.5% hyperglycemic, P < .024; 28.6%
      hypoglycemic vs 10.3% normoglycemic P < .049). Survival analysis showed a
      significantly lower estimated survival for hypoglycemic patients (36 days) than
      for normoglycemic patients (54 days) or hyperglycemic patients (45 days;
      hypoglycemic vs hyperglycemic, P < .019; hypoglycemic vs normoglycemic, P < .007;
      hyperglycemic vs normoglycemic, P < .477). CONCLUSION: Hypoglycemia is associated
      with increased mortality in patients with acute decompensated liver cirrhosis. It
      is not yet clear whether hypoglycemia is jointly responsible for the increased
      short-term mortality of patients with acute decompensated liver cirrhosis or is
      only a consequence of the severity of the disease or the complications.

PMID- 24332993
TI  - Epidemiologic features, risk factors, and outcome of sepsis in stroke patients
      treated on a neurologic intensive care unit.
AB  - PURPOSE: Because of the immune-suppressive effect of cerebral damage, stroke
      patients are at high risk for infections. These might result in sepsis, which is
      the major contributor to intensive care unit (ICU) mortality. Although there are
      numerous studies on infections in stroke patients, the role of sepsis as a
      poststroke complication is unknown. METHODS: We retrospectively analyzed
      incidence of and risk factors for sepsis acquisition as well as outcome
      parameters of 238 patients with ischemic or hemorrhagic strokes consecutively
      admitted to the neurologic ICU in a tertiary university hospital between January
      1, 2009, and December 31, 2010. Basic demographic and clinical data including
      microbiological parameters as well as factors describing stroke severity (eg,
      lesion volume and National Institute of Health stroke scale score) were recorded
      and included into the analysis. The diagnosis of sepsis was based on the criteria
      of the German Sepsis Society. RESULTS: We identified 30 patients (12.6%) with
      sepsis within the first 7 days from stroke onset. The lungs were the most
      frequent source of infection (93.3%), and gram-positive organisms were dominating
      the microbiologic spectrum (52.4%). Comorbidities (chronic obstructive pulmonary
      disease and immunosuppressive disorders) and Simplified Acute Physiology Score II
      but none of the factors describing stroke severity were independent predictors of
      sepsis acquisition. Sepsis was associated with a significantly worse prognosis,
      leading to a 2-fold increased mortality rate during in-hospital care (36.7% vs
      18.8%) and after 3 months (56.5% vs 28.5%), but only in the subgroup of
      supratentorial hemorrhages, it was an independent predictor of in-hospital and 3
      month mortality. Other factors significantly associated with death in a
      multivariate analysis were chronic obstructive pulmonary disease, malignancies
      (in-hospital mortality only), and Simplified Acute Physiology Score II (3-month
      mortality only) for ischemia and heart failure (in-hospital mortality only),
      National Institute of Health stroke scale score (in-hospital mortality only), and
      stroke volume for hemorrhages, respectively. CONCLUSIONS: Sepsis seems to be a
      frequent complication of stroke patients requiring neurologic ICU treatment.
      Predictors of sepsis acquisition in our study were comorbidities and severity of
      deterioration of physiological status, but not stroke severity. A better
      understanding of risk factors is important for prevention and early recognition,
      whereas knowledge of outcome may help in prognosis prediction. Further studies
      are needed to clarify the optimal preventive treatment for these patients.

PMID- 24332994
TI  - Thermodilution vs pressure recording analytical method in hemodynamic stabilized
      patients.
AB  - PURPOSE: Many mini-invasive devices to monitor cardiac output (CO) have been
      introduced and, among them, the pressure recording analytical method (PRAM). The
      aim of this study was to assess the agreement of PRAM with the intermittent
      transpulmonary thermodilution and continuous pulmonary thermodilution in
      measuring CO in hemodynamically stabilized patients. MATERIALS AND METHODS: This
      is a prospective clinical study in a mixed medical-surgical intensive care unit
      (ICU) and in a postcardiac surgical ICU. Forty-eight patients were enrolled: 32
      patients to the medical-surgical ICU monitored with PiCCO (Pulsion Medical System
      AG, Munich, Germany) and 16 were cardiac patients monitored with Vigilance
      (Edwards Lifesciences, Irvine, CA). RESULTS: A total of 112 measurements were
      made. Ninety-six comparisons of paired CO measurements were made in patients
      hospitalized in medical-surgical ICU; 16, in cardiac surgical patients. The mean
      Vigilance-CO was 4.49 +/- 0.99 L/min (range, 2.80-5.90 L/min), and the mean PRAM
      CO was 4.27 +/- 0.88 L/min (range, 2.85-6.19 L/min). The correlation coefficient
      between Vigilance-CO and PRAM-CO was 0.83 (95% confidence interval, 0.57-0.94; P
      < .001). The bias was 0.22 +/- 0.55 L/min with limits of agreement between 0.87
      and 1.30 L/min. The percentage error was 25%. Mean TP-CO was 6.78 +/- 2.04 L/min
      (range, 4.12-11.27 L/min), and the mean PRAM-CO was 6.11 +/- 2.18 L/min (range,
      2.82-10.90 L/min). The correlation coefficient between PiCCO-CO and PRAM-CO was
      0.91 (95% confidence interval, 0.83-0.96; P < .0001). The bias was 0.67 +/- 0.89
      L/min with limits of agreement -1.07 and 2.41 L/min. The coefficient of variation
      for PiCCO was 4% +/- 2%, and the coefficient of variation for PRAM was 10% +/-
      8%. The percentage error was 28%. CONCLUSIONS: The PRAM system showed good
      agreement with pulmonary artery catheter and PiCCO in hemodynamically stabilized
      patients.

PMID- 24332995
TI  - The impact of low hemoglobin levels and transfusion on critical care patients
      with severe ischemic stroke: STroke: RelevAnt Impact of HemoGlobin, Hematocrit
      and Transfusion (STRAIGHT)--an observational study.
AB  - PURPOSE: Optimal management of hemoglobin (Hb) and red blood cell transfusion
      (RBCT) in neurologic intensive care unit (NICU) patients has not been determined
      yet. Here we aimed to investigate the impact of anemia and transfusion activity
      in patients who had acute ischemic stroke. MATERIALS AND METHODS: A retrospective
      analysis of clinical, laboratory, and outcome data of patients with severe acute
      ischemic stroke treated on our NICU between 2004 and 2011 was performed. RESULTS:
      Of 109 patients, 97.2% developed anemia and 33% received RBCT. Significant
      correlations were found between NICU length of stay (NICU LOS) and lowest (nadir)
      Hb (correlation coefficient, -0.42, P < .001), Hb decrease (0.52, P < .001),
      nadir hematocrit (Hct; -0.43, P < .001), and Hct decrease (0.51, P < .001).
      Duration of mechanical ventilation (MV) was strongly associated with both nadir
      Hb (-0.41, P < .001) and decrease (0.42, P < .001) and nadir Hct (-0.43, P <
      .001) and decrease (0.40, P < .001). Red blood cell transfusion correlated with
      NICU LOS (0.33, P < .001) and with duration of MV (0.40, P < .001). None of these
      hematologic parameters correlated with in-hospital mortality or 90-day outcome.
      The linear regression model showed number of RBCT (0.29, P = .008), nadir Hb (
      0.18, P = .049), Hb decrease (0.33, P < .001), nadir Hct (-0.18, P = .03), and
      Hct decrease (0.29, P < .001) to be independent predictors of NICU LOS. Duration
      of MV was also independently predicted by number of RBC transfusions (0.29, P <
      .001), nadir Hb (-0.20, P = .02), Hb decrease (0.25, P = .002), nadir Hct (-0.21,
      P = .015), and Hct decrease (0.26, P < .001). CONCLUSIONS: Low and further
      decreasing Hb and Hct levels as well as RBCT activity are associated with
      prolonged NICU stay and duration of MV but not with mortality or long-term
      outcome. Our findings do not justify using a more aggressive transfusion practice
      at present.

PMID- 24332996
TI  - The impact of switching to the new global lung function initiative equations on
      spirometry results in the UK CF registry.
AB  - BACKGROUND: The Quanjer et al. Global Lung Function Initiative (GLI)-2012 multi
      ethnic all-age reference equations for spirometry are endorsed by all major
      respiratory societies and are the new gold standard. Before the GLI equations are
      implemented for use in CF patients, the impact of changing equations from those
      currently used needs to be better understood. METHODS: Annual review data
      submitted to the UK CF Trust Registry between 2007 and 2011 were used to
      calculate %predicted FEV1, FVC and FEV1/FVC using three widely used reference
      equations (Wang-Hankinson and Knudson) and the new GLI-2012 equations. RESULTS:
      Overall, Knudson and Wang equations overestimated %predicted values in paediatric
      patients, such that a greater proportion of patients had lung function values in
      the normal range. Within individual patients, the impact of switching equations
      varied greatly depending on the patients' age, and which equations were used.
      CONCLUSIONS: A unified approach to interpreting spirometric lung function
      measurements would help facilitate more appropriate comparison both within and
      between centres and countries. Interpretation of longitudinal measurements using
      a continuous reference equation across all-ages, like the GLI, may further
      improve our understanding of CF lung disease.

PMID- 24332998
TI  - Improving collection efficiency through remote monitoring of charity assets.
AB  - Collection costs associated with servicing a major UK charity's donation banks
      and collecting unsold goods from their retail shops can account for up to 20% of
      the overall income gained. Bank and shop collections are commingled and are
      typically made on fixed days of the week irrespective of the amounts of materials
      waiting to be collected. Using collection records from a major UK charity, this
      paper considers what vehicle routing and scheduling benefits could accrue if bank
      and shop servicing requirements were monitored, the former using remote sensing
      technology to allow more proactive collection scheduling. A vehicle routing and
      scheduling algorithm employing tabu search methods was developed, and suggested
      time and distance savings of up to 30% over the current fixed schedules when a
      minimum bank and shop fill level of between 50% and 60% was used as a collection
      trigger. For the case study investigated, this led to a potential revenue gain of
      5% for the charity and estimated CO2 savings of around 0.5 tonnes per week across
      the fleet of six heterogeneous vehicles.

PMID- 24332997
TI  - Iron supplementation does not worsen respiratory health or alter the sputum
      microbiome in cystic fibrosis.
AB  - BACKGROUND: Iron supplementation for hypoferremic anemia could potentiate
      bacterial growth in the cystic fibrosis (CF) lung, but clinical trials testing
      this hypothesis are lacking. METHODS: Twenty-two adults with CF and hypoferremic
      anemia participated in a randomized, double-blind, placebo-controlled, crossover
      trial of ferrous sulfate 325mg daily for 6weeks. Iron-related hematologic
      parameters, anthropometric data, sputum iron, Akron Pulmonary Exacerbation Score
      (PES), and the sputum microbiome were serially assessed. Fixed-effect models were
      used to describe how ferrous sulfate affected these variables. RESULTS: Ferrous
      sulfate increased serum iron by 22.3% and transferrin saturation (TSAT) by 26.8%
      from baseline (p<0.05) but did not affect hemoglobin, sputum iron, Akron PES, and
      the sputum microbiome. CONCLUSIONS: Low-dose ferrous sulfate improved
      hypoferremia without correcting anemia after 6weeks. We did not observe
      significant effects on sputum iron, Akron PES, and the sputum microbiome.
      Although we did not identify untoward health effects of iron supplementation, a
      larger blinded randomized controlled trial would be needed to fully demonstrate
      safety.

PMID- 24332999
TI  - Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by
      TACE/ADAM-17: a positive feedback mechanism in the RAS.
AB  - Angiotensin converting enzyme (ACE) 2 is a key negative regulator of the renin
      angiotensin system where it metabolizes angiotensin (Ang) II into Ang 1-7. We
      hypothesize that Ang II suppresses ACE2 by increasing TNF-alpha converting enzyme
      (TACE) activity and ACE2 cleavage. Ang II infusion (1.5 mg/kg/day) in wild-type
      mice for 2 weeks resulted in substantial decrease in myocardial ACE2 protein
      levels and activity with corresponding increase in plasma ACE2 activity,
      prevented by AT1R blockade. Ang II resulted in AT1R-mediated increase in
      myocardial TACE expression and activity, and membrane translocation of TACE. Ang
      II treatment in Huh7 cells exhibited AT1R-dependent metalloproteinase mediated
      shedding of ACE2 while transfection with siTACE prevented shedding of ACE2;
      cardiomyocyte-specific deletion of TACE also prevented shedding of ACE2. Reactive
      oxygen species played a key role since p47(phox)KO mice were resistant to Ang II
      induced TACE phosphorylation and activation with preservation of myocardial ACE2
      which dampened Ang II-induced cardiac dysfunction and hypertrophy. In conclusion,
      Ang II induces ACE2 shedding by promoting TACE activity as a positive feedback
      mechanism whereby Ang II facilitates the loss of its negative regulator, ACE2. In
      HF, elevated plasma ACE2 activity likely represents loss of the protective
      effects of ACE2 in the heart.

PMID- 24333000
TI  - Value of prostate multiparametric magnetic resonance imaging for predicting
      biopsy results in first or repeat biopsy.
AB  - AIM: To assess multiparametric magnetic resonance imaging (mp-MRI) in predicting
      prostate biopsy results. MATERIALS AND METHODS: Patients who underwent mp-MRI
      prior to prostate biopsy were prospectively included. The prostate was subdivided
      into 14 sectors and mp-MRI findings assessed using a five-level subjective
      suspicion score (SSS). Biopsy included targeted samples of abnormal sectors and
      systematic samples of normal peripheral zone sectors. RESULTS: Two hundred and
      eighty-eight patients were included [153 biopsy naive, 135 with negative (n = 51)
      or positive (n = 84) prior biopsy]. Biopsy was positive in 168 patients. mp-MRI
      area under the receiver operating characteristic (ROC) curve (AUC) was 69.1% (95%
      CI: 67.1-70.9%), 72.5% (95% CI: 69.5-76%), and 73.8% (95% CI: 68.3-79.3%) at per
      sector, per lobe, and per patient analysis, respectively. At the per sector
      level, the AUC was significantly larger if detection was limited to cancers with
      a Gleason score of >=7 (72.6%; 95% CI: 69.8-75.8%; p < 0.01) or >=8 (87.1%; 95%
      CI: 78.3-95.7%; p < 0.01). mp-MRI performance was significantly influenced by
      prostate volume (p = 0.02), the presence of a concordant hypoechoic area (p <
      0.001), but not by prostate-specific antigen (PSA) value, status of prior biopsy,
      or radiologists' experience. SSS was significantly associated with the Gleason
      score in true-positive lobes and patients (p < 0.0001). Using a SSS threshold of
      >=3, cancer was missed in 13/102 lobes and 4/72 patients with cancers of Gleason
      score >=7. CONCLUSION: mp-MRI provides a good detection of cancers with a Gleason
      score of >=7 in candidates suitable for prostate biopsy.

PMID- 24333001
TI  - Practical applications of digital tomosynthesis of the chest.
AB  - Digital tomosynthesis is a radiographic technique that generates a number of
      coronal raw images of a patient from a single pass of the x-ray tube.
      Tomosynthesis provides some of the tomographic benefits of computed tomography
      (CT), but at a much lower dose of radiation and cost when compared to CT. This
      review illustrates the range of practical applications of digital tomosynthesis
      of the chest. 

PMID- 24333003
TI  - Effect of intrinsic motivation on cognitive performance in schizophrenia: a pilot
      study.

PMID- 24333002
TI  - Light-activated serotonin for exploring its action in biological systems.
AB  - Serotonin (5-HT) is a neuromodulator involved in regulating mood, appetite,
      memory, learning, pain, and establishment of left-right (LR) asymmetry in
      embryonic development. To explore the role of 5-HT in physiology, we have created
      two forms of "caged" 5-HT, BHQ-O-5HT and BHQ-N-5HT. When exposed to 365 or 740 nm
      light, BHQ-O-5HT releases 5-HT through one- or two-photon excitation,
      respectively. BHQ-O-5HT mediated changes in neural activity in cultured mouse
      primary sensory neurons and the trigeminal ganglion and optic tectum of intact
      zebrafish larvae in the form of high-amplitude spiking in response to light. In
      Xenopus laevis embryos, light-activated 5-HT increased the occurrence of LR
      patterning defects. Maximal rates of LR defects were observed when 5-HT was
      released at stage 5 compared with stage 8. These experiments show the potential
      for BHQ-caged serotonins in studying 5-HT-regulated physiological processes. 

PMID- 24333004
TI  - Relationship between diminished expression and cognitive impairment in first
      episode schizophrenia: a prospective three-year follow-up study.
AB  - BACKGROUND: Diminished expression (DE) is a core sub-domain of negative symptoms
      construct in schizophrenia. There is limited, yet inconsistent data regarding DE
      and its associations with cognition, particularly in the early illness course.
      This study aimed to examine cross-sectional and longitudinal relationships of DE
      with cognitive functions in first-episode schizophrenia utilizing a prospective
      design. METHOD: Ninety-three Hong Kong Chinese aged 18 to 55 years presenting
      with first-episode schizophrenia-spectrum disorder were studied. Severity of DE
      was measured as sum of individual item scores indicative of affect flattening and
      alogia. Symptom evaluation was conducted at intake, after clinical stabilization
      of first psychotic episode, at 12, 24 and 36 months. Cognitive functions were
      evaluated at clinical stabilization, 12, 24 and 36 months. RESULTS: DE was
      significantly correlated with various cognitive functions in successive follow-up
      assessments. Regression analyses adjusting confounding effects of sex, pre-morbid
      adjustment, duration of untreated psychosis and chlorpromazine equivalents showed
      that DE was associated with performance on verbal fluency at 12 (p<0.01) and 24
      months (p<0.05), visual reproduction at 24 (p<0.05) and 36 months (p<0.01),
      logical memory at 36 months (p<0.05) and Modified Wisconsin Card Sorting test at
      24 (p<0.05) and 36 months (p<0.05). Neither cross-lagged associations between DE
      and cognition nor significant correlations between changes in these two domains
      over three years were observed. CONCLUSIONS: DE and cognitive functions were
      correlated concurrently but no longitudinal associations between these two
      domains could be demonstrated. Our findings indicated that DE and cognitive
      impairment represented relatively independent domains of the illness with
      potentially distinctive therapeutic implications.

PMID- 24333005
TI  - Psychiatric symptom differences in people with schizophrenia associated with
      substantial lifetime substance use but no current substance use disorder.

PMID- 24333006
TI  - New players in high fat diet-induced obesity: LETM1 and CTMP.
AB  - OBJECTIVE: Obesity contributes to insulin resistance and is a risk factor for
      diabetes. C-terminal modulator protein (CTMP) and leucine zipper/EF-hand
      containing transmembrane protein 1 (LETM1) have been reported to influence the
      phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) signaling pathway via the
      modulation of PKB activity, a key player for insulin signaling. However, it
      remains unclear whether CTMP and LETM1 are associated with PI3K/PKB signaling in
      mouse models of obesity. MATERIALS/METHODS: To address this question, we used two
      different mouse models of obesity, including high-fat diet (HFD)-induced diabetic
      mice and genetically modified obese mice (ob/ob mice). The levels of insulin
      signaling molecules in these mice were determined by immunohistochemical and
      Western blot analyses. The involvement of CTMP and LETM1 in PI3K/PKB signaling
      was investigated in HEK293 cells by transient transfection and adenovirus
      mediated infection. RESULTS: We found that the levels of insulin receptor,
      phosphorylated PKB, and LETM1 were lower and the level of CTMP was higher in the
      adipose tissue of obese mice on an HFD compared to lean mice on a chow diet.
      Similar results were obtained in ob/ob mice. In HEK293 cells, the activation of
      PKB increased the LETM1 level, and inhibition of PKB increased the CTMP level.
      The overexpression of CTMP suppressed the insulin-induced increase in PKB
      phosphorylation, which was abrogated by co-overexpression with LETM1. CONCLUSION:
      These results suggest that CTMP and LETM1 may participate in impaired insulin
      signaling in the adipose tissue of obese mice, raising the possibility that these
      parameters may serve as new candidate biomarkers or targets in the development of
      new therapeutic approaches for diabetes.

PMID- 24333007
TI  - Effect of Nicotinic acid/Laropiprant in the lipoprotein(a) concentration with
      regard to baseline lipoprotein(a) concentration and LPA genotype.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] is a lipoprotein in which apolipoproteinB-100
      is linked to apolipoprotein(a) [apo(a)]. Significant variation in Lp(a)
      concentration is specific to LPA gene, which codes for apo(a). Nicotinic acid
      (NA) is used for treatment of dyslipidemias, and the lowering effect of NA on
      Lp(a) has been previously reported. OBJECTIVE: To evaluate the Lp(a) lowering
      effect of 1g/20mg and 2g/40mgday of Nicotinic acid/Laropiprant in subjects with
      different baseline Lp(a) concentrations and depending on the LPA genotype.
      METHODS: In an open-label, 10-week study, 1g/20mgday of NA/Laropiprant for 4weeks
      followed by 6weeks of 2g/40mgday conducted at 3 centers in Spain, 82 subjects
      were enrolled. Patients were studied at baseline and at the end of both treatment
      periods and were enrolled in three groups: normal Lp(a) (<50mg/dL), high Lp(a)
      (50-120mg/dL) and very high Lp(a) (>120mg/dL). The LPA genetic polymorphism was
      analyzed by a real-time PCR. RESULTS: There was a significant difference in LPA
      genotypes among Lp(a) concentration groups and an inverse and significant
      correlation between baseline Lp(a) concentration and LPA genotype was found (R=
      0.372, p<0.001). There were a significant decrease in total cholesterol,
      triglycerides, LDL cholesterol, apo B and Lp(a), and a significant increase in
      HDL cholesterol after NA/Laropiprant treatment, without changes in BMI. However,
      there were no statistical differences in percentage variation of analyzed
      variables depending on LPA genotype. CONCLUSION: LPA genotype is a major
      determinant of Lp(a) baseline concentration. However, the lipid lowering effect
      of NA is not related to LPA genotype.

PMID- 24333008
TI  - Breast cancer chemoprevention: little progress in practice?

PMID- 24333010
TI  - 2,3,5,6-Tetramethylpyrazine of Ephedra sinica regulates melanogenesis and
      inflammation in a UVA-induced melanoma/keratinocytes co-culture system.
AB  - BACKGROUND: 2,3,5,6-Tetramethylpyrazine (TMP) is known as a composition of
      Ephedra sinica and it has been used in the treatment of several disorders such as
      asthma, heart failure, rhinitis, and urinary incontinence. It has been reported
      that TMP inhibits melanoma metastasis and suppression angiogenesis by VEGF.
      OBJECTIVE: The inhibitory activity of melanogenic proteins by TMP was confirmed
      in UVA-induced melanoma/keratinocyte co-culture system in this paper. METHODS:
      The melanin content, cell viability and cytokines release such as TNFalpha, IL
      1beta, IL-8 and GM-CSF were measured by ELISA assay. In addition, TRP1, MITF and
      MAPK signaling protein expression were also evaluated by Western blotting
      analysis. RESULTS: Decreasing melanogenic factors (TRP1, MITF, and MAPK) and
      factors (TNFalpha, IL-1beta, IL-8, and GM-CSF) improving skin cancer and
      inflammation were identified. CONCLUSION: It suggests that TMP can serve as a
      potent candidate for regulation of melanogenesis.

PMID- 24333011
TI  - Early paediatric scald surgery--a cost effective dermal preserving surgical
      protocol for all childhood scalds.

PMID- 24333012
TI  - Ocular residual astigmatism: effects of demographic and ocular parameters in
      myopic laser in situ keratomileusis.
AB  - PURPOSE: To analyze the influence of demographic and ocular factors on ocular
      residual astigmatism (ORA) in myopic laser in situ keratomileusis (LASIK).
      SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. DESIGN:
      Retrospective cross-sectional data analysis. METHODS: Eyes of consecutive myopic
      patients scheduled for LASIK were studied to evaluate the influence on
      preexisting ORA of age, sex, ocular dominance, subjective cylinder and
      topographic astigmatism, subjective sphere, and mesopic pupil size. The ORA was
      determined using Alpins vector analysis. Two subgroups, defined by the ratio of
      ORA to preoperative refractive cylinder (R), were formed: ORA:R >= 1.0 and ORA:R
      <1.0). RESULTS: The study comprised 2991 eyes (2991 patients). The mean ORA was
      0.75 diopter (D) +/- 0.39 (SD) (range 0.00 to 2.00 D); 1372 (46%) eyes had ORA of
      1.00 D or more. Ordinary least square estimations and odds ratios showed that
      subjective sphere, male sex, and dominant eye were negative predictors of the
      degree of preoperative ORA, while increasing age and larger mesopic pupils did
      not indicate ORA orientation. With-the-rule astigmatism meridian was more likely
      in eyes with low ORA, while oblique and against-the-rule meridians were related
      to high ORA. CONCLUSIONS: The preoperative assessment of refractive surgery
      candidates should consider the interaction between topographic, refractive, and
      ORA because corneal refractive surgery is more successful in eyes in which the
      cylinder mainly originates from the anterior cornea. The current data can help
      identify patients at high risk for having a significant difference between
      subjective cylinder and topographic astigmatism. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 24333013
TI  - Series of fibrinous inflammation after implantation of capsular tension rings.
AB  - PURPOSE: To analyze the cause of fibrinous inflammation in eyes with capsular
      tension rings (CTRs) after cataract surgery. SETTING: Department of
      Ophthalmology, University Medical Center, Johannes Gutenberg-University Mainz,
      Mainz, Germany. DESIGN: Retrospective case series. METHODS: High-performance
      liquid chromatography was implemented to eliminate impurities. One CTR was
      explanted for microbiologic examination. The pH values of the CTR and the storage
      solution were analyzed, Seldi and Maldi tests were performed, as well as toxicity
      tests with immortal cell lines. Material batches were analyzed. The organic
      carbon content of CTRs, detergents, and storage solutions was checked. The
      presence of endotoxins was excluded with the limulus amoebocyte lysate test. Gas
      chromatography with mass selective detector excluded the presence of extractable
      organic substances. An inductively coupled plasma analysis scanned for inorganic
      substances. The microbial count in operating rooms, smear tests, and
      microbiologic examinations of technical devices were initiated. RESULTS: Analyses
      found no pathological findings. After intensive systemic and topical treatment
      with antibiotics and steroids, clinical findings improved. The implantation of
      CTRs was stopped immediately. No further cases occurred. CONCLUSIONS: Fibrinous
      inflammations after implantation of CTRs were unknown until now. Contamination
      and/or irritation by detergents or the material CTR itself were excluded,
      indicating mechanical or toxic irritation by the CTR. FINANCIAL DISCLOSURE: No
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 24333015
TI  - C1orf163/RESA1 is a novel mitochondrial intermembrane space protein connected to
      respiratory chain assembly.
AB  - Oxidative phosphorylation (OXPHOS) in mitochondria takes place at the inner
      membrane, which folds into numerous cristae. The stability of cristae depends,
      among other things, on the mitochondrial intermembrane space bridging complex.
      Its components include inner mitochondrial membrane protein mitofilin and outer
      membrane protein Sam50. We identified a conserved, uncharacterized protein,
      C1orf163 [SEL1 repeat containing 1 protein (SELRC1)], as one of the proteins
      significantly reduced after the knockdown of Sam50 and mitofilin. We show that
      C1orf163 is a mitochondrial soluble intermembrane space protein. Sam50 depletion
      affects moderately the import and assembly of C1orf163 into two protein complexes
      of approximately 60kDa and 150kDa. We observe that the knockdown of C1orf163
      leads to reduction of levels of proteins belonging to the OXPHOS complexes. The
      activity of complexes I and IV is reduced in C1orf163-depleted cells, and we
      observe the strongest defects in the assembly of complex IV. Therefore, we
      propose C1orf163 to be a novel factor important for the assembly of respiratory
      chain complexes in human mitochondria and suggest to name it RESA1 (for
      RESpiratory chain Assembly 1). 

PMID- 24333014
TI  - The glaucoma-associated olfactomedin domain of myocilin forms polymorphic fibrils
      that are constrained by partial unfolding and peptide sequence.
AB  - The glaucoma-associated olfactomedin domain of myocilin (myoc-OLF) is a recent
      addition to the growing list of disease-associated amyloidogenic proteins.
      Inherited, disease-causing myocilin variants aggregate intracellularly instead of
      being secreted to the trabecular meshwork, which is a scenario toxic to
      trabecular meshwork cells and leads to early onset of ocular hypertension, the
      major risk factor for glaucoma. Here we systematically structurally and
      biophysically dissected myoc-OLF to better understand its amyloidogenesis. Under
      mildly destabilizing conditions, wild-type myoc-OLF adopts non-native structures
      that readily fibrillize when incubated at a temperature just below the transition
      for tertiary unfolding. With buffers at physiological pH, two main endpoint
      fibril morphologies are observed: (a) straight fibrils common to many amyloids
      and (b) unique micron-length, ~300 nm or larger diameter, species that lasso
      oligomers, which also exhibit classical spectroscopic amyloid signatures. Three
      disease-causing variants investigated herein exhibit non-native tertiary
      structures under physiological conditions, leading to a variety of growth rates
      and a fibril morphologies. In particular, the well-documented D380A variant,
      which lacks calcium, forms large circular fibrils. Two amyloid-forming peptide
      stretches have been identified, one for each of the main fibril morphologies
      observed. Our study places myoc-OLF within the larger landscape of the amylome
      and provides insight into the diversity of myoc-OLF aggregation that plays a role
      in glaucoma pathogenesis.

PMID- 24333016
TI  - Core structures of ubiquitin dictate its dynamics and function.

PMID- 24333018
TI  - Prokaryotic ancestry of eukaryotic protein networks mediating innate immunity and
      apoptosis.
AB  - Protein domains characteristic of eukaryotic innate immunity and apoptosis have
      many prokaryotic counterparts of unknown function. By reconstructing interactomes
      computationally, we found that bacterial proteins containing these domains are
      part of a network that also includes other domains not hitherto associated with
      immunity. This network is connected to the network of prokaryotic signal
      transduction proteins, such as histidine kinases and chemoreceptors. The network
      varies considerably in domain composition and degree of paralogy, even between
      strains of the same species, and its repetitive domains are often amplified
      recently, with individual repeats sharing up to 100% sequence identity. Both
      phenomena are evidence of considerable evolutionary pressure and thus compatible
      with a role in the "arms race" between host and pathogen. In order to investigate
      the relationship of this network to its eukaryotic counterparts, we performed a
      cluster analysis of organisms based on a census of its constituent domains across
      all fully sequenced genomes. We obtained a large central cluster of mainly
      unicellular organisms, from which multicellular organisms radiate out in two main
      directions. One is taken by multicellular bacteria, primarily cyanobacteria and
      actinomycetes, and plants form an extension of this direction, connected via the
      basal, unicellular cyanobacteria. The second main direction is taken by animals
      and fungi, which form separate branches with a common root in the alpha
      proteobacteria of the central cluster. This analysis supports the notion that the
      innate immunity networks of eukaryotes originated from their endosymbionts and
      that increases in the complexity of these networks accompanied the emergence of
      multicellularity. 

PMID- 24333017
TI  - Flexibility within the heads of muscle myosin-2 molecules.
AB  - We show that negative-stain electron microscopy and image processing of
      nucleotide-free (apo) striated muscle myosin-2 subfragment-1 (S1), possessing one
      light chain or both light chains, is capable of resolving significant amounts of
      structural detail. The overall appearance of the motor and the lever is similar
      in rabbit, scallop and chicken S1. Projection matching of class averages of the
      different S1 types to projection views of two different crystal structures of apo
      S1 shows that all types most commonly closely resemble the appearance of the
      scallop S1 structure rather than the methylated chicken S1 structure. Methylation
      of chicken S1 has no effect on the structure of the molecule at this resolution:
      it too resembles the scallop S1 crystal structure. The lever is found to vary in
      its angle of attachment to the motor domain, with a hinge point located in the so
      called pliant region between the converter and the essential light chain. The
      chicken S1 crystal structure lies near one end of the range of flexion observed.
      The Gaussian spread of angles of flexion suggests that flexibility is driven
      thermally, from which a torsional spring constant of ~23 pN.nm/rad2 is estimated
      on average for all S1 types, similar to myosin-5. This translates to apparent
      cantilever-type stiffness at the tip of the lever of 0.37 pN/nm. Because this
      stiffness is lower than recent estimates from myosin-2 heads attached to actin,
      we suggest that binding to actin leads to an allosteric stiffening of the motor
      lever junction.

PMID- 24333019
TI  - Increased cortisol levels in hair of recent Ecstasy/MDMA users.
AB  - Previous research has revealed an acute 8-fold increase in salivary cortisol
      following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not
      known to what extent repeated usage impacts upon activity of the hypothalamic
      pituitary-adrenal axis over a more prolonged period of time. This study
      investigated the integrated cortisol levels in 3-month hair samples from recent
      Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants
      (53 males, 48 females; mean age 21.75 years) completed the University of East
      London recreational drug use questionnaire, modified to cover the past 3-months
      of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3
      months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user
      controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair
      cortisol levels were observed to be significantly higher in recent heavy MDMA
      users (mean = 55.0 +/- 80.1 pg/mg), compared to recent light MDMA users (19.4 +/-
      16.0 pg/mg; p=0.015), and to non-users (13.8 +/- 6.1 pg/mg; p<0.001). Hence the
      regular use of Ecstasy/MDMA was associated with almost 4-fold raised hair
      cortisol levels, in comparison with non-user controls. The present results are
      consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts
      that repeated stimulant drug use may increase cortisol production acutely, and
      result in greater deposits of the hormone in hair. These data may also help
      explain the neurocognitive, psychiatric, and other psychobiological problems of
      some abstinent users. Future study design and directions for research concerning
      the psychoneuroendocrinological impact of MDMA are also discussed.

PMID- 24333020
TI  - Lobular breast cancer in a CDH1 splice site mutation carrier: case report and
      review of the literature.

PMID- 24333021
TI  - Experience with the CyberKnife for intracranial stereotactic radiosurgery:
      analysis of dosimetry indices.
AB  - We evaluated coverage, dose homogeneity, dose conformity, and dose gradient in
      CyberKnife VSI treatment plans. Several dosimetric indices were calculated, and
      the results were compared with those of previous publications. The effect of
      target volume on the radiosurgical treatment indices selected was also
      investigated. The study population comprised the first 40 patients treated at our
      department from March 2011 to September 2012. Dosimetric indices were calculated
      and compared with published results for other frame-based and frameless
      intracranial stereotactic radiotherapy techniques. A comparison of the indices
      confirmed the ability of the CyberKnife VSI system to provide very high-quality
      dosing plans. The results were independent of target volume for coverage,
      homogeneity, and dose conformity. However, a dependence on target volume was
      observed for the dose-gradient indices analyzed. Based on the indices proposed,
      CyberKnife provides very good treatment plans and compares favorably with other
      techniques in most cases. However, greater consensus on the radiosurgery indices
      calculated would be desirable to facilitate comparison of the various techniques
      or the same techniques when applied by different users. 

PMID- 24333009
TI  - Anastrozole for prevention of breast cancer in high-risk postmenopausal women
      (IBIS-II): an international, double-blind, randomised placebo-controlled trial.
AB  - BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and
      development of new contralateral tumours in postmenopausal women. We assessed the
      efficacy and safety of the aromatase inhibitor anastrozole for prevention of
      breast cancer in postmenopausal women who are at high risk of the disease.
      METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women
      aged 40-70 years from 18 countries into an international, double-blind,
      randomised placebo-controlled trial. To be eligible, women had to be at increased
      risk of breast cancer (judged on the basis of specific criteria). Eligible women
      were randomly assigned (1:1) by central computer allocation to receive 1 mg oral
      anastrozole or matching placebo every day for 5 years. Randomisation was
      stratified by country and was done with blocks (size six, eight, or ten). All
      trial personnel, participants, and clinicians were masked to treatment
      allocation; only the trial statistician was unmasked. The primary endpoint was
      histologically confirmed breast cancer (invasive cancers or non-invasive ductal
      carcinoma in situ). Analyses were done by intention to treat. This trial is
      registered, number ISRCTN31488319. FINDINGS: 1920 women were randomly assigned to
      receive anastrozole and 1944 to placebo. After a median follow-up of 5.0 years
      (IQR 3.0-7.1), 40 women in the anastrozole group (2%) and 85 in the placebo group
      (4%) had developed breast cancer (hazard ratio 0.47, 95% CI 0.32-0.68, p<0.0001).
      The predicted cumulative incidence of all breast cancers after 7 years was 5.6%
      in the placebo group and 2.8% in the anastrozole group. 18 deaths were reported
      in the anastrozole group and 17 in the placebo group, and no specific causes were
      more common in one group than the other (p=0.836). INTERPRETATION: Anastrozole
      effectively reduces incidence of breast cancer in high-risk postmenopausal women.
      This finding, along with the fact that most of the side-effects associated with
      oestrogen deprivation were not attributable to treatment, provides support for
      the use of anastrozole in postmenopausal women at high risk of breast cancer.
      FUNDING: Cancer Research UK, the National Health and Medical Research Council
      Australia, Sanofi-Aventis, and AstraZeneca.

PMID- 24333022
TI  - Effect of Acuros XB algorithm on monitor units for stereotactic body radiotherapy
      planning of lung cancer.
AB  - Stereotactic body radiotherapy (SBRT) is a curative regimen that uses
      hypofractionated radiation-absorbed dose to achieve a high degree of local
      control in early stage non-small cell lung cancer (NSCLC). In the presence of
      heterogeneities, the dose calculation for the lungs becomes challenging. We have
      evaluated the dosimetric effect of the recently introduced advanced dose
      calculation algorithm, Acuros XB (AXB), for SBRT of NSCLC. A total of 97 patients
      with early-stage lung cancer who underwent SBRT at our cancer center during last
      4 years were included. Initial clinical plans were created in Aria Eclipse
      version 8.9 or prior, using 6 to 10 fields with 6-MV beams, and dose was
      calculated using the anisotropic analytic algorithm (AAA) as implemented in
      Eclipse treatment planning system. The clinical plans were recalculated in Aria
      Eclipse 11.0.21 using both AAA and AXB algorithms. Both sets of plans were
      normalized to the same prescription point at the center of mass of the target. A
      secondary monitor unit (MU) calculation was performed using commercial program
      RadCalc for all of the fields. For the planning target volumes ranging from 19 to
      375cm(3), a comparison of MUs was performed for both set of algorithms on field
      and plan basis. In total, variation of MUs for 677 treatment fields was
      investigated in terms of equivalent depth and the equivalent square of the field.
      Overall, MUs required by AXB to deliver the prescribed dose are on an average 2%
      higher than AAA. Using a 2-tailed paired t-test, the MUs from the 2 algorithms
      were found to be significantly different (p < 0.001). The secondary independent
      MU calculator RadCalc underestimates the required MUs (on an average by 4% to 5%)
      in the lung relative to either of the 2 dose algorithms. 

PMID- 24333023
TI  - Small RNAs in prokaryotes and eukaryotes: a lesson for human immunologists:
      comment on "Diversity, evolution, and therapeutic applications of small RNAs in
      prokaryotic and eukaryotic immune systems" by Edwin L. Cooper and Nicola
      Overstreet.

PMID- 24333024
TI  - In vitro and in vivo antitumor effects of Peanut agglutinin through induction of
      apoptotic and autophagic cell death.
AB  - In this study we unravel the mechanism underlying the antitumorigenic effects of
      Peanut agglutinin (PNA) isolated from Arachis hypogea in Dalton's lymphoma (DL)
      bearing mice and elucidated the mechanism in vitro in HeLa cells. In vivo PNA
      administration at 1 and 2 mg/kg body weight reduced DL proliferation with
      increase in autophagic and apoptotic characteristics. In vitro data showed that
      PNA at 0.1-100 MUg/ml dose exhibit selective antiproliferative activity on
      various cancer cell lines without displaying cytotoxic effect on normal cells.
      However, heat denatured PNA failed to show any antiproliferative activity.
      Moreover, PNA was found to induce autophagic and apoptotic cell death in HeLa
      cells. Exponential increase in reactive oxygen species (ROS) was proved to be the
      master signal for promoting PNA induced cell death in HeLa cells. Interestingly,
      when HeLa cells were pre-exposed with N-acetylcysteine (NAC) and followed to PNA
      treatment, there was sharp decline in autophagy, apoptosis and a concomitant
      abrogation of antiproliferative potential. PNA at lower doses was also seen to
      inflict senescence. Hence, this common culinary item derived molecule whose
      discovery dates back to late 1970s was for the first time evaluated
      mechanistically in vivo and in vitro as a novel naturally occurring therapeutic
      agent against cancer.

PMID- 24333026
TI  - The composition of tribofilms produced on metal-on-metal hip bearings.
AB  - Following wear testing in a hip simulator, the bearing surfaces of 36 mm metal on
      metal total hip replacements showed the formation of tribochemical layers. These
      layers were investigated in a transmission electron microscope, and analysis was
      performed using electron energy loss spectroscopy, energy dispersive x-rays and
      selected area electron diffraction. The tribofilm formed at the edge of the wear
      scar was 100 s of nanometres thick and contained cobalt sulphide particles
      embedded within. The film itself was rich in carbon, and appeared to contain no
      long range graphitic ordering when analysed with electron energy loss
      spectroscopy, and the spectra gathered from the tribofilm closely resembled those
      collected from amorphous carbon. The location at which the most substantial
      tribological layers formed may be explained by the formation of a blunt wedge at
      the edge of the wear scar following conformal changes to the bearing surfaces.

PMID- 24333025
TI  - Engineering of a bio-functionalized hybrid off-the-shelf heart valve.
AB  - Currently available heart valve replacements are limited in long-term performance
      or fail due to leaflet thickening, lack of growth or remodeling potential. In
      order to address these issues, it is necessary to mimic multiple factors of the
      native valvular extracellular matrix (ECM) such as architecture, mechanical
      behavior and biochemical signals. Here, we successfully generated an electrospun
      PEGdma-PLA scaffold adapted to the structure and mechanical properties of native
      valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells
      (VECs) were seeded on the scaffold and when cultured under physiological
      conditions in a bioreactor, the construct performed like a native leaflet. Atomic
      force microscopy (AFM) was employed to obtain detailed mechanical information
      from the leaflets, which enabled the first layer-specific measurement of the
      Young's modulus. Interestingly, spongiosa stiffness was much lower compared to
      the fibrosa and ventricularis. Moreover, investigations into human fetal heart
      valve development identified collagen type I and versican as important structural
      proteins. As a proof of principle, these proteins were introduced to the
      scaffold, demonstrating the ability to bio-functionalize the hybrid valve based
      on natures' blueprint. 

PMID- 24333027
TI  - Graphene oxide doped conducting polymer nanocomposite film for electrode-tissue
      interface.
AB  - One of the most significant components for implantable bioelectronic devices is
      the interface between the microelectrodes and the tissue or cells for disease
      diagnosis or treatment. To make the devices work efficiently and safely in vivo,
      the electrode-tissue interface should not only be confined in micro scale, but
      also possesses excellent electrochemical characteristic, stability and
      biocompatibility. Considering the enhancement of many composite materials by
      combining graphene oxide (GO) for its multiple advantages, we dope graphene oxide
      into poly(3,4-ethylenedioxythiophene) (PEDOT) forming a composite film by
      electrochemical deposition for electrode site modification. As a consequence, not
      only the enlargement of efficient surface area, but also the development of
      impedance, charge storage capacity and charge injection limit contribute to the
      excellent electrochemical performance. Furthermore, the stability and
      biocompatibility are confirmed by numerously repeated usage test and cell
      proliferation and attachment examination, respectively. As electrode-tissue
      interface, this biomaterial opens a new gate for tissue engineering and
      implantable electrophysiological devices.

PMID- 24333028
TI  - Modulation of chondrocyte functions and stiffness-dependent cartilage repair
      using an injectable enzymatically crosslinked hydrogel with tunable mechanical
      properties.
AB  - We developed an injectable hydrogel system to evaluate the effect of hydrogel
      stiffness on chondrocyte cellular functions in a three-dimensional (3D)
      environment and its subsequent influence on ectopic cartilage formation and early
      stage osteochondral defect repair in a rabbit model. The hydrogels, composed of
      gelatin-hydroxyphenylpropionic acid (Gtn-HPA) conjugate, were formed using
      oxidative coupling of HPA moieties catalyzed by hydrogen peroxide (H2O2) and
      horseradish peroxidase (HRP). The storage modulus (G') of the hydrogels, which
      was tunable by changing the H2O2 and Gtn-HPA concentrations, ranged from 570 Pa
      to 2750 Pa. It was found that the cellular functions of chondrocytes encapsulated
      in hydrogels, including cell proliferation, biosynthesis of collagen and sulfated
      glycosaminoglycans (sGAG), as well as gene expression of type I (Col-I) and type
      II collagen (Col-II), were strongly affected by the stiffness of the hydrogels.
      Of note, chondrocytes cultured within the Gtn-HPA hydrogel of medium stiffness
      (G' = 1000 Pa) produced highest level of sGAG production, as well as highest
      ratio of Col-II to Col-I gene expression among the Gtn-HPA hydrogels of different
      stiffness. Consistent with the results from in vitro and in vivo ectopic
      cartilage formation, osteochondral defect repair in a rabbit model showed
      stiffness-dependent tissue repair, with defects implanted with chondrocytes in
      hydrogels of medium stiffness having markedly more hyaline cartilage formation,
      smoother surface and better integration with adjacent cartilage, compared to
      defects treated with hydrogels of low or high stiffness. These results suggest
      that the tunable stiffness of Gtn-HPA hydrogels modulates chondrocyte cellular
      functions, and has a dramatic impact on cartilage tissue histogenesis and repair.

PMID- 24333029
TI  - Quantitating distance-dependent, indirect cell-cell interactions with a
      multilayered phospholipid polymer hydrogel.
AB  - Multilayered polymer hydrogels containing living cells were assembled for
      assessing the distance-dependent effects of soluble factors secreted by stroma
      cells on tumor cell cycle progression in vitro. A layer of tumor cells and a
      layer of stroma cells were separated with finely controlled spacing in a
      multilayered sandwich composed of a 2-methacryloyloxyethyl phosphorylcholine
      polymer and poly(vinyl alcohol) hydrogel. We demonstrated the utility of this
      tool for investigating intercellular communication between human cervical cancer
      HeLa cells and supportive stromal L929 fibroblast cells in co-culture. Time-lapse
      microscopic analyses of HeLa cells showed short distances (15 MUm) between tumor
      cells and stroma cells induced a continuous increase in the percentage of HeLa
      cells in the S/G2/M phases of the cell cycle, while longer distances (70 MUm)
      between the cells caused a slower increase followed by a sharp increase in the
      percentage of cells in S/G2/M phases. One possible explanation is gradient
      formation in the diffusion-dominant multilayer hydrogels by water-soluble factors
      such as those inducing growth, differentiation, and proliferation. This study
      provides insights into the potential effects of diffusion of soluble factors and
      related distance-dependent effects on cell behavior, which may contribute to the
      design of future co-culture systems.

PMID- 24333030
TI  - Sesquiterpenoid glycosides from glandular trichomes of the wild tomato relative
      Solanum habrochaites.
AB  - Profiles of terpenoid glycoside metabolites in glandular trichomes of Solanum
      habrochaites LA1777 leaves were generated using ultrahigh performance liquid
      chromatography/time-of-flight mass spectrometry with multiplexing of non
      selective collision-induced dissociation (CID). Profiling data suggested a
      diverse group of 52 sesquiterpenoid glycosides, and fragment ions observed in
      both non-selective CID mass spectra and true tandem mass spectrometry (MS/MS)
      product ion spectra documented variation in extent of glycosylation and the
      presence of malonate or acetate esters. Up to 10 isomers were detected for some
      metabolites. Malonate and acetate esters of three sesquiterpene diol glucosides
      and one unmodified diglucoside were purified using reversed phase semipreparative
      HPLC and analyzed and identified using 1D and 2D NMR and mass spectrometry. All
      four of the isolated products were glucosides of campheranane-2,12-diol. 

PMID- 24333031
TI  - A young root-specific gene (ArMY2) from horseradish encoding a MYR II myrosinase
      with kinetic preference for the root-specific glucosinolate gluconasturtiin.
AB  - The pungent taste of horseradish is caused by isothiocyanates which are released
      from glucosinolates by myrosinases. These enzymes are encoded by genes belonging
      to one of two subfamilies, termed MYR I and MYR II, respectively. A MYR II-type
      myrosinase gene was identified for the first time in horseradish. The gene termed
      ArMY2 was only expressed in young roots. A full-length cDNA encoding a myrosinase
      termed ArMy2 was isolated and heterologously expressed in Pichia pastoris. The
      recombinant His-tagged enzyme was characterized biochemically. Substrate affinity
      was 5 times higher towards gluconasturtiin than towards sinigrin. Gluconasturtiin
      was found to be the most abundant glucosinolate in young horseradish roots while
      sinigrin dominated in storage roots and leaves. This indicates that a specialized
      glucosinolate-myrosinase defense system might be active in young roots. 

PMID- 24333032
TI  - The authors' reply.

PMID- 24333033
TI  - Prevalence of Axis-1 psychiatric (with focus on depression and anxiety) disorder
      and symptomatology among non-medical prescription opioid users in substance use
      treatment: systematic review and meta-analyses.
AB  - Non-medical prescription opioid use (NMPOU) constitutes a substantial clinical
      and public health concern in North America. Although there is evidence of
      elevated rates of mental health problems among people with NMPOU, the extent of
      these correlations specifically in treatment samples has not been systematically
      assessed. A systematic review and meta-analysis were conducted for Axis-1
      psychiatric diagnoses and symptoms with a principal focus on depression and
      anxiety disorders in substance use treatment samples reporting NMPOU at admission
      to treatment (both criteria within past 30days). 11 unique studies (all from
      either the United States or Canada) met inclusion criteria and were included in
      the meta-analysis. The pooled prevalence of 'any' mental health problems (both
      diagnosis and symptoms) among substance abuse treatment patients reporting NMPOU
      was 43% (95% CI: 32%-54%; I(2) for inter-study heterogeneity: 99.5%). The pooled
      prevalence of depression diagnosis among substance abuse treatment patients
      reporting NMPOU was 27% (95% CI: 9%-45%; I(2): 99.2%); the pooled prevalence of
      anxiety diagnosis in the sample was 29% (95% CI: 14%-44%; I(2): 98.7%). The
      prevalence rates of psychiatric problems (both diagnosis and symptoms),
      depression diagnosis and anxiety diagnosis are disproportionately high in
      substance use treatment samples reporting NMPOU relative to general population
      rates. Adequate and effective clinical strategies are needed to address co
      occurring NMPOU and mental health in substance use treatment systems, especially
      given rising treatment demand for NMPOU. Efforts are needed to better understand
      the temporal and causal relationships among NMPOU, mental health problems, and
      treatment seeking in order to improve interventions. 

PMID- 24333034
TI  - A multiple motive/multi-dimensional approach to measure smokeless tobacco
      dependence.
AB  - BACKGROUND: Unlike various research studies conducted to address dependence among
      smokers, only a few studies have examined smokeless tobacco (ST) dependence. The
      Fagerstrom Tolerance Questionnaire (FTQ) and Fagerstrom Test for Nicotine
      Dependence (FTND) based scales are the most widely used measures of nicotine
      dependence for both ST users and smokers. These scales were initially developed
      to measure physical dependence and tolerance and not to assess other salient
      dimensions of dependence such as craving, compulsion, or withdrawal, as defined
      by DSM-IV and ICD-10. The aim of this study is to develop and validate a
      multidimensional scale that has better content coverage, factor structure, and
      psychometric properties to measure dependence among ST users. METHODS: 100 adult
      male smokeless tobacco users were recruited through email distribution lists and
      community referral. Participants completed three different nicotine dependence
      questionnaires and provided information related to their tobacco use and
      demographic characteristics. They also provided a saliva sample for cotinine
      measurement. In order to develop the new ST scale, subscales and items were
      selected based on correlation and factor analysis of the modified WISDM-68.
      Reliability and validity of the new scale, Oklahoma Scale for Smokeless Tobacco
      Dependence (OSSTD) were also assessed. RESULTS: The new ST scale identified seven
      latent constructs including 23 items to measure ST dependence. Internal
      consistency as measured by Cronbach's coefficient (alpha=0.925) indicated better
      reliability of OSSTD than FTND-ST. Concurrent validity of OSSTD as evaluated by
      comparing it with dependence diagnosis and FTND-ST was affirmative. There was a
      significant correlation between the OSSTD total score and the cotinine levels and
      tobacco use characteristics among study participants. CONCLUSION: OSSTD possesses
      better psychometric properties and provides an effective and efficient tool to
      measure ST dependence as a multidimensional construct.

PMID- 24333035
TI  - A cognitive behavioral smoking abstinence intervention for adults with chronic
      pain: a randomized controlled pilot trial.
AB  - Current evidence suggests it may be difficult for patients with chronic pain to
      quit smoking and, based on previous formative work, a 7-session individual and
      group-based cognitive behavioral (CB) intervention was developed. The primary aim
      of this randomized controlled pilot trial was to test the hypothesis that
      abstinence at month 6 would be greater among patients with chronic pain who
      received the CB intervention compared to a control condition. Upon admission to a
      3-week interdisciplinary pain treatment (IPT) program, patients were randomized
      to receive the CB intervention (n=30) or the control condition (n=30). The 7-day
      point prevalence of self-reported smoking status was assessed at week 3 (upon
      completion of the 3-week IPT program) and at month 6 in an intent-to-treat
      analysis. At week 3, 30% (n=9) of patients in the CB condition were abstinent
      from smoking compared to 10% (n=3) in the control group (P=.104). At month 6, 20%
      (n=6) of patients who received the CB intervention were abstinent compared to
      none in the control group (P=.024). At week 3, a significant group by time
      interaction effect was found where the CB patients experienced greater
      improvements in self-efficacy from baseline compared to the control group
      (P=.002). A greater proportion of patients randomized to the CB group completed
      the IPT program (P=.052). The findings of this pilot trial suggest that
      integration of a CB-based smoking abstinence intervention into ongoing pain
      therapy may be an effective treatment for smokers with chronic pain. 

PMID- 24333036
TI  - Typology of alcohol users based on longitudinal patterns of drinking.
AB  - OBJECTIVE: Worldwide, alcohol is the most commonly used psychoactive substance.
      However, heterogeneity among alcohol users has been widely recognized. This paper
      presents a typology of alcohol users based on an implementation of idiographic
      methodology to examine longitudinal daily and cyclic (weekly) patterns of alcohol
      use at the individual level. METHOD: A secondary data analysis was performed on
      the pre-intervention data from a large randomized control trial. A time series
      analysis was performed at the individual level, and a dynamic cluster analysis
      was employed to identify homogenous longitudinal patterns of drinking behavior at
      the group level. The analysis employed 180 daily observations of alcohol use in a
      sample of 177 alcohol users. RESULTS: The first order autocorrelations ranged
      from -.76 to .72, and seventh order autocorrelations ranged from -.27 to .79.
      Eight distinct profiles of alcohol users were identified, each characterized by a
      unique configuration of first and seventh autoregressive terms and longitudinal
      trajectories of alcohol use. External validity of the profiles confirmed the
      theoretical relevance of different patterns of alcohol use. Significant
      differences among the eight subtypes were found on gender, marital status,
      frequency of drug use, lifetime alcohol dependence, family history of alcohol use
      and the Short Index of Problems. CONCLUSIONS: Our findings demonstrate that
      individuals can have very different temporal patterns of drinking behavior. The
      daily and cyclic patterns of alcohol use may be important for designing tailored
      interventions for problem drinkers.

PMID- 24333037
TI  - Prevalence of unassisted quit attempts in population-based studies: a systematic
      review of the literature.
AB  - AIMS: The idea that most smokers quit without formal assistance is widely
      accepted, however, few studies have been referenced as evidence. The purpose of
      this study is to systematically review the literature to determine what
      proportion of adult smokers report attempting to quit unassisted in population
      based studies. METHODS: A four stage strategy was used to conduct a search of the
      literature including searching 9 electronic databases (PUBMED, MEDLINE (OVID)
      (1948-), EMBASE (1947-), CINAHL, ISI Web of Science with conference proceedings,
      PsycINFO (1806-), Scopus, Conference Papers Index, and Digital Dissertations),
      the gray literature, online forums and hand searches. RESULTS: A total of 26
      population-based prevalence studies of unassisted quitting were identified, which
      presented data collected from 1986 through 2010, in 9 countries. Unassisted quit
      attempts ranged from a high of 95.3% in a study in Christchurch, New Zealand,
      between 1998 and 1999, to a low of 40.6% in a national Australian study conducted
      between 2008 and 2009. In 24 of the 26 studies reviewed, a majority of quit
      attempts were unassisted. CONCLUSIONS: This systematic review demonstrates that a
      majority of quit attempts in population-based studies to date are unassisted.
      However, across and within countries over time, it appears that there is a trend
      toward lower prevalence of making quit attempts without reported assistance or
      intervention.

PMID- 24333039
TI  - Reciprocal effects of alcohol and nicotine in smoking cessation treatment
      studies.
AB  - OBJECTIVE: Smoking and alcohol use are highly related; as such the present study
      investigated whether alcohol use is associated with failure in tobacco cessation
      attempts. We first examined the self-reported drinking behavior and smoking over
      the course of a year at a basic level. Next, we addressed two hypotheses to
      characterize this relationship at a deeper level: (Hypothesis 1) Alcohol use
      would be lower for those who attempted to quit smoking (quit for one or more
      days) during the year compared to those who never quit, and (Hypothesis 2) for
      those who relapsed to smoking after a quit increases in alcohol consumption would
      be positively associated with increases in smoking. METHOD: Subjects were
      participants in two smoking cessation programs. One group of participants (N=139)
      was part of a smoking cessation study in alcohol dependent smokers in early
      recovery and the other group of participants (N=163) was drawn from a smoking
      cessation study for HIV positive smokers. H1 was tested using t-tests. For H2, a
      time series analysis examined relationships between smoking and alcohol use
      within person over a one year period. For H1 and for H2, the analyses utilized
      bivariate time series procedures. Timeline follow-back data allowed for detailed
      daily reports of both tobacco and alcohol use. RESULTS: In the overall sample,
      there was no difference in alcohol use between those who stopped smoking and
      those who never stopped. However, when broken up by study, a difference was found
      in the alcohol dependent sample such that mean drinks were higher for those who
      stopped compared to those who never stopped smoking (H1). The results indicated a
      high number of positive significant cross-correlations between tobacco and
      alcohol use such that one substance predicted current, as well as past and future
      use of the alternate substance. Same-day cross-correlations were the most common,
      and dissipated with time (H2). CONCLUSIONS: This analysis provided insights into
      the proximal influence of one substance on the other. Alcohol is related to
      relapse in smoking cessation attempts. It is important that smoking cessation
      efforts in alcohol using populations consider alcohol use in treatment.

PMID- 24333038
TI  - Web-based intervention to change perceived norms of college student alcohol use
      and sexual behavior on spring break.
AB  - The purpose of the present study was to evaluate an adapted web-based multi
      component personalized feedback intervention to reduce college student alcohol
      use and risky sexual behavior during Spring Break. This is one of the first
      interventions focused on Spring Break alcohol use and related sexual behavior.
      Personalized feedback intervention components addressed intentions, expected
      consequences, norms, motivations, protective behavioral strategies, and pacts
      with friends. Participants were college students (N=263; 55% women) between the
      ages of 18 and 21 who planned to go on a Spring Break trip with their friends.
      Effects were not significant in reducing alcohol use or sexual behavior during
      Spring Break or some of the proposed intervention mechanisms. However, consistent
      results showed that the intervention succeeded in reducing perceived social norms
      for Spring Break drinking and sexual behavior. Findings suggest that changing
      norms alone is not sufficient for changing risk behavior during this event and
      alternative strategies are needed to impact other putative mediators. 

PMID- 24333040
TI  - Herpes Simplex epithelial keratitis associated with daily disposable contact lens
      wear.
AB  - PURPOSE: To report a case of epithelial Herpes Simplex keratitis in a patient
      wearing daily disposable contact lenses. METHOD: Case report. RESULTS: A 30-year
      old female contact lens wearer presented to the emergency clinic with a painful,
      red left eye associated with an acute reduction of vision over 48 h. On
      examination, confluent dendritic ulcers were present on the cornea. Neither
      pertinent ocular nor medical history was obtained to explain such a dramatic
      clinical presentation. CONCLUSION: Contact lens wear was the only risk factor
      identified, perhaps resulting in deviation of the immune response at the ocular
      surface, with consequent extensive dendritic ulceration.

PMID- 24333041
TI  - Tug-of-war between opposing molecular motors explains chromosomal oscillation
      during mitosis.
AB  - Chromosomes move towards and away from the centrosomes during the mitosis. This
      oscillation is observed when the kinetochore, a specific protein structure on the
      chromosome is captured by centrosome-nucleated polymer called microtubules. We
      present a computational model, incorporating activities of various molecular
      motors and microtubule dynamics, to demonstrate the observed oscillation. The
      model is robust and is not restricted to any particular cell type. Quantifying
      the average velocity, amplitude and periodicity of the chromosomal oscillation,
      we compare numerical results with the available experimental data. Our analysis
      supports a tug-of-war like mechanism between opposing motors that changes the
      course of chromosomal oscillation. It turns out that, various modes of
      oscillation can be fully understood by assembling the dynamics of molecular
      motors. Near the stall regime, when opposing motors are engaged in a tug-of-war,
      sufficiently large kinetochore-microtubule generated force may prolong the stall
      durations. 

PMID- 24333042
TI  - Where are obese people happier?

PMID- 24333043
TI  - A major phospholipase A2 from Daboia russelii russelii venom shows potent
      anticoagulant action via thrombin inhibition and binding with plasma
      phospholipids.
AB  - This is the first report on antithrombin effects of a phospholipase A2 (RVAPLA2)
      purified from venom of Daboia russelii russelii. The N-terminal sequence as well
      as in-gel tryptic digested peptides of RVAPLA2 showed significant homology with
      PLA2s from Russell's viper venom. RVAPLA2 demonstrated highest specific activity
      in hydrolyzing phosphatidylcholine (1.8 * 10(6) U/mg) with Km and Vmax values of
      0.61 mM and 132.3 MUmol/min, respectively. RVAPLA2 exerted dose-dependent
      catalytic and strong anticoagulant activities; however, studies indicated
      dissociation of its catalytic and anticoagulant sites. The anticoagulant action
      of RVAPLA2 was partially contributed by catalytic hydrolysis of plasma
      phospholipids. RVAPLA2 showed strong anticoagulant effect via thrombin inhibition
      with a Ki value of 380 nM as well as by binding to pro-coagulant phospholipids of
      plasma. In ex-vivo conditions, RVAPLA2 (1.0 MUM) was non-hemolytic and non
      cytotoxic to mammalian cells. It did not inhibit the collagen-induced aggregation
      of platelets. RVAPLA2 at a dose of 5 mg/kg was not lethal to mice after 48 h of
      injection. It demonstrated in vivo anticoagulant activity possibly due to
      targeting thrombin and binding with plasma phospholipids. 

PMID- 24333044
TI  - Biaxial Q-shearing of 27Al 3QMAS NMR spectra: insight into the structural
      disorder of framework aluminosilicates.
AB  - In this contribution, we present the application potentiality of biaxial Q
      shearing of (27)Al 3QMAS NMR spectra in the analysis of structural defects of
      aluminium units in aluminosilicates. This study demonstrates that the combination
      of various shearing transformations of the recorded (27)Al 3QMAS NMR spectra
      enables an understanding of the broadening processes of the correlation signals
      of disordered framework aluminosilicates, for which a wide distribution of (27)Al
      MAS NMR chemical shifts and quadrupolar parameters (i.e., second-order
      quadrupolar splitting and quadrupole-induced chemical shifts) can be expected. By
      combining the suitably selected shearing transformation procedures, the
      mechanisms of the formation of local defects in aluminosilicate frameworks,
      including Al/Si substitution effects in the next-nearest neighbouring T-sites,
      variations in bond angles, and/or variations in the physicochemical nature of
      charge-balancing counter-ions, can be identified. The proposed procedure has been
      extensively tested on a range of model aluminosilicate materials (kyanite, gamma
      alumina, metakaolin, analcime, chabazite, natrolite, phillipsite, mordenite,
      zeolite A, and zeolite Y). 

PMID- 24333046
TI  - Periscopes, snorkels and chimneys: no smoke without fire?

PMID- 24333045
TI  - The angiogenic effects of ischemic conditioning in experimental critical limb
      ischemia.
AB  - OBJECTIVES: Ischemic conditioning (IC) is a method of angiogenic stimulus for
      limb ischemia. Here, we aimed to investigate the effects of short-term repeated
      ischemic stimulus on critical lower limb ischemic injury. METHODS: Rats were
      divided into four groups consisting of 40 animals in each group: sham, ischemia,
      local IC, and remote IC groups. Right-leg critical limb ischemia was achieved
      through ligation of the iliac artery and vein in male Sprague-Dawley rats except
      the sham group. Repeated transient ischemia using the tourniquet method was used
      for IC of lower extremities in the local and remote groups. IC was performed on
      the right leg for the local group and on the left leg for the remote group. Ten
      rats in each group were sacrificed for evaluation on days 1, 7, 14, and 30.
      Endothelial progenitor cell (EPC) counts were measured. Gastrocnemius muscles
      were evaluated for the degree of ischemia. Laser Doppler blood flow measurements
      were performed in order to make comparison between the blood flows of the limbs
      of the groups. RESULTS: The blood flow in the right limb of rats in the sham
      (1.65 perfusion units [PU]) and local IC (1.67 PU) groups was significantly
      higher than the ischemic group (1.17 PU) (p = .001 and p = .022 respectively).
      The levels of EPCs in the ischemia (1.09 +/- 0.5) and remote IC groups (1.36 +/-
      0.8) were significantly higher than the sham (0.38 +/- 0.2) group on day 7 (p =
      .026 and p = .002 respectively). Remote IC and local IC groups exhibited
      increased histopathological ischemia on day 7 when compared with sham group (p =
      .001, p = .01 respectively). The angiogenic scores on the 7th, 14th and 30th days
      for local IC and remote IC groups were significantly higher than sham and
      ischemia groups. CONCLUSIONS: IC seems to be the potent activator of angiogenesis
      in ischemic tissue. This study provides preliminary data showing that repeated
      short ischemic stimuli may reduce critical ischemic injury by promoting
      angiogenesis.

PMID- 24333047
TI  - Review: maternal and placental antioxidant response to preeclampsia - impact on
      vasoactive eicosanoids.
AB  - The abnormally developed placenta is believed to be the pathophysiological cause
      of preeclampsia (PE). The resulting malperfusion of the placenta in PE can be
      associated with fluctuations in oxygen levels, leading to oxidative stress. How
      then do the placenta and the circulatory system of the mother adapt and respond
      to the increased oxidative challenge associated with PE? Many antioxidant systems
      have been shown to be upregulated or downregulated in the placenta and/or the
      maternal circulation during PE. Such altered antioxidant response can lead to
      increased lipid peroxidation. Oxidation of arachidonoyl residues in phospholipids
      generates bioactive lipids such as F2-isoprostanes, which are known
      vasoconstrictors. The consequences of changes in antioxidant status can also
      affect signal transduction and enzymatic pathways related to eicosanoid
      synthesis. 

PMID- 24333048
TI  - A comprehensive analysis of the human placenta transcriptome.
AB  - As the conduit for nutrients and growth signals, the placenta is critical to
      establishing an environment sufficient for fetal growth and development. To
      better understand the mechanisms regulating placental development and gene
      expression, we characterized the transcriptome of term placenta from 20 healthy
      women with uncomplicated pregnancies using RNA-seq. To identify genes that were
      highly expressed and unique to the placenta we compared placental RNA-seq data to
      data from 7 other tissues (adipose, breast, hear, kidney, liver, lung, and smooth
      muscle) and identified several genes novel to placental biology (QSOX1, DLG5, and
      SEMA7A). Semi-quantitative RT-PCR confirmed the RNA-seq results and
      immunohistochemistry indicated these proteins were highly expressed in the
      placental syncytium. Additionally, we mined our RNA-seq data to map the relative
      expression of key developmental gene families (Fox, Sox, Gata, Tead, and Wnt)
      within the placenta. We identified FOXO4, GATA3, and WNT7A to be amongst the
      highest expressed members of these families. Overall, these findings provide a
      new reference for understanding of placental transcriptome and can aid in the
      identification of novel pathways regulating placenta physiology that may be
      dysregulated in placental disease. 

PMID- 24333049
TI  - Expression, purification, and projection structure by single particle electron
      microscopy of functional human TRPM4 heterologously expressed in Xenopus laevis
      oocytes.
AB  - Despite efforts implicating the cationic channel transient receptor potential
      melastatin member 4 (TRPM4) to cardiac, nervous, and immunological pathologies,
      little is known about its structure and function. In this study, we optimized the
      requirements for purification and extraction of functional human TRPM4 protein
      and investigated its supra-molecular assembly. We selected the Xenopus laevis
      oocyte expression system because it lacks endogenous TRPM4 expression, it is
      known to overexpress functional human membrane channels, can be used for
      structure-function analysis within the same system, and is easily scaled to
      improve yield and develop moderate throughput capabilities through the use of
      robotics. Negative-stain electron microscopy (EM) revealed various sized low
      resolution particles. Single particle analysis identified the majority of the
      projections represented the monomeric form with additional oligomeric structures
      potentially characterized as tetramers. Two-electrode voltage clamp
      electrophysiology demonstrated that human TRPM4 is functionally expressed at the
      oocyte plasma membrane. This study opens the door for medium-throughput screening
      and structure-function determination of this important therapeutically relevant
      target. 

PMID- 24333050
TI  - Outcomes after institution of a new oxytocin infusion protocol during the third
      stage of labor and immediate postpartum period.

PMID- 24333051
TI  - Pregnancy is associated with a decrease in pharyngeal but not tracheal or
      laryngeal cross-sectional area: a pilot study using the acoustic reflection
      method.
AB  - BACKGROUND: The risk of difficult upper airway access is increased during
      pregnancy, especially in labor. Changes in upper airway calibre have been poorly
      studied during pregnancy. The acoustic reflection method is a non-invasive
      technique that allows a longitudinal assessment of the cross-sectional area of
      the upper airway from the mouth to carina. We used this technique to evaluate
      upper airway calibre during normal pregnancy. METHODS: We conducted a
      prospective, single centre, observational study with a clinical and upper airway
      acoustic reflection method evaluation of healthy women during the first, second
      and third trimesters of pregnancy, and up to two days and one month after
      delivery. RESULTS: Fifty women participated to the study. The mean pharyngeal
      cross-sectional area decreased between the first and third trimesters (P < 0.001)
      with no significant change of the minimal and mean tracheal cross-sectional
      areas. The Mallampati score increased during pregnancy between the first and
      third trimesters (P< 0.001). CONCLUSION: Using measurements with the acoustic
      reflection method, normal pregnancy is associated with a significant reduction in
      the cross-sectional area of the pharynx and a concomitant increase in the
      Mallampati score. No change was observed in the minimal and mean tracheal cross
      sectional areas.

PMID- 24333052
TI  - Effect of ritonavir-induced cytochrome P450 3A4 inhibition on plasma fentanyl
      concentrations during patient-controlled epidural labor analgesia: a
      pharmacokinetic simulation.
AB  - BACKGROUND: Ritonavir inhibition of cytochrome P450 3A4 decreases the elimination
      clearance of fentanyl by 67%. We used a pharmacokinetic model developed from
      published data to simulate the effect of sample patient-controlled epidural labor
      analgesic regimens on plasma fentanyl concentrations in the absence and presence
      of ritonavir-induced cytochrome P450 3A4 inhibition. METHODS: Fentanyl absorption
      from the epidural space was modeled using tanks-in-series delay elements.
      Systemic fentanyl disposition was described using a three-compartment
      pharmacokinetic model. Parameters for epidural drug absorption were estimated by
      fitting the model to reported plasma fentanyl concentrations measured after
      epidural administration. The validity of the model was assessed by comparing
      predicted plasma concentrations after epidural administration to published data.
      The effect of ritonavir was modeled as a 67% decrease in fentanyl elimination
      clearance. Plasma fentanyl concentrations were simulated for six sample patient
      controlled epidural labor analgesic regimens over 24 h using ritonavir and
      control models. Simulated data were analyzed to determine if plasma fentanyl
      concentrations producing a 50% decrease in minute ventilation (6.1 ng/mL) were
      achieved. RESULTS: Simulated plasma fentanyl concentrations in the ritonavir
      group were higher than those in the control group for all sample labor analgesic
      regimens. Maximum plasma fentanyl concentrations were 1.8 ng/mL and 3.4 ng/mL for
      the normal and ritonavir simulations, respectively, and did not reach
      concentrations associated with 50% decrease in minute ventilation. CONCLUSION:
      Our model predicts that even with maximal clinical dosing regimens of epidural
      fentanyl over 24 h, ritonavir-induced cytochrome P450 3A4 inhibition is unlikely
      to produce plasma fentanyl concentrations associated with a decrease in minute
      ventilation.

PMID- 24333054
TI  - Between thoughts and actions: motivationally salient cues invigorate mental
      action in the human brain.
AB  - The maintenance of goal-directed behavior relies upon a cascade of covert mental
      actions including motor imagery and planning. Here we investigated how cues
      imbued with motivational salience can invigorate motor imagery networks preceding
      action. We adapted the Pavlovian-to-instrumental (PIT) paradigm to explore this
      by substituting motor action with motor imagery. Thus, reward was contingent upon
      a given level of imagery-induced neural activity using real-time fMRI. We found
      that the concomitant presentation of reward-related cues during motor imagery not
      only enhanced neural responses in motivational centers (ventral striatum and
      extended amygdala) but also exerted a motivational effect in the imagery network
      itself. Moreover, functional connectivity between ventral striatum (but not
      extended amygdala) and motor cortex was heightened during imagery in the presence
      of the reward-related cue. The concurrent activation of "value" and "action"
      networks may illuminate the neural process that links motivational cues to
      desires and urges to obtain goals. 

PMID- 24333053
TI  - Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo
      define a mechanism for network oscillations.
AB  - Theta-gamma network oscillations are thought to represent key reference signals
      for information processing in neuronal ensembles, but the underlying synaptic
      mechanisms remain unclear. To address this question, we performed whole-cell (WC)
      patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the
      dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials
      at low frequency, consistent with sparse coding in the dentate gyrus. GCs were
      exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents
      (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory
      postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs
      exhibited coherence with the field potential predominantly in the theta frequency
      band, whereas IPSCs showed coherence primarily in the gamma range. Action
      potentials in GCs were phase locked to network oscillations. Thus, theta-gamma
      modulated synaptic currents may provide a framework for sparse temporal coding of
      information in the dentate gyrus. 

PMID- 24333055
TI  - Autonomous mechanism of internal choice estimate underlies decision inertia.
AB  - Our choice is influenced by choices we made in the past, but the mechanism
      responsible for the choice bias remains elusive. Here we show that the history
      dependent choice bias can be explained by an autonomous learning rule whereby an
      estimate of the likelihood of a choice to be made is updated in each trial by
      comparing between the actual and expected choices. We found that in perceptual
      decision making without performance feedback, a decision on an ambiguous stimulus
      is repeated on the subsequent trial more often than a decision on a salient
      stimulus. This inertia of decision was not accounted for by biases in motor
      response, sensory processing, or attention. The posterior cingulate cortex and
      frontal eye field represent choice prediction error and choice estimate in the
      learning algorithm, respectively. Interactions between the two regions during the
      intertrial interval are associated with decision inertia on a subsequent trial. 

PMID- 24333056
TI  - Survival of blood transfusion recipients identified by a look-back investigation.
AB  - BACKGROUND: Survival of blood transfusion recipients is a critical consideration
      in assessing the outcomes of transfusion. Data from the USA on the short- and
      long-term survival of recipients are limited. MATERIALS AND METHODS: Blood
      product recipients were identified through a look-back study of Creutzfeldt-Jakob
      disease. Survival data were obtained from searches of the National Death Index or
      the Social Security Death Master File. Short- and long-term survival of
      recipients was analysed through descriptive statistics, Kaplan-Meier survival
      analysis, and stratified Cox proportional hazard modelling. RESULTS: This study
      includes data from 575 blood product recipients. One half of the recipients died
      within the first year of transfusion and the median time to death was 1.1 years.
      Survival rates at 5, 10, 15, 20, and 25 years after transfusion were 32%, 22%,
      15%, 12%, and 9%, respectively. Survival rates varied with age at transfusion and
      type of component received, but not by gender. Survival after transfusion varied
      by year of transfusion, with recipients transfused in 1980-1989 having longer
      post-transfusion survival than those transfused in 2000-2010 (p=0.049). In
      multivariate models, the type of component transfused, but not the year of
      transfusion, was a significant predictor of survival among recipients; this
      effect varied by age. DISCUSSION: We provide an estimate of survival time from a
      geographically diverse sample of blood product recipients in the USA. Predictors
      of post-transfusion survival are numerous and complex, and may include year of
      transfusion and type of component transfused.

PMID- 24333057
TI  - The AQP1 mutation c.601delG causes the Co-negative phenotype in four patients
      belonging to the Romani (Gypsy) ethnic group.
AB  - BACKGROUND: The Colton blood group antigens Co(a), Co(b) and Co3 are encoded by
      the AQP1 gene which produces a water channel forming integral protein. The
      extremely rare Co-deficiency enables immunisation against the Co3 isoantigen.
      MATERIALS AND METHODS: Four patients from different regions of Europe who belong
      to the ethnic minority of Romani (Gypsy) presented with irregular antibodies
      against a high frequency red blood cell antigen. Positive cross-matches with all
      red blood cells tested were reported. An Anti-Co3 antibody was identified as the
      cause of incompatibility in the four cases. The genetic background was determined
      by polymerase chain reaction typing with sequence-specific primers and by DNA
      sequencing. RESULTS: The Co(a-b-) phenotype was confirmed in the four patients
      despite the fact that genotyping revealed the CO*01 allele of the AQP1 gene. A
      homozygous AQP1 c.601delG mutation, leading to a frame shift and producing a
      premature stop in the next codon, was responsible for the Co-negative phenotype
      in all four cases. While one patient was successfully transfused with blood from
      his sibling with the identical mutation, another case, a baby affected by
      haemolytic disease of the newborn, recovered without transfusion. DISCUSSION:
      Despite the difficulties in undertaking a population study to determine the
      prevalence of this AQP1 c.601delG allele in the ethnic minority of Romani, the
      observations described in this report clearly suggest an accumulation of this
      mutation, which causes the Co(a-b-) phenotype, in Romani (Gypsy) patients.
      Further studies are necessary to prove such an accumulation.

PMID- 24333058
TI  - Molecular immunohaematology round table discussions at the AABB Annual Meeting,
      Boston 2012.

PMID- 24333059
TI  - Topical application of platelet supernatant gel in the management of radiotherapy
      induced mucositis: a case report.

PMID- 24333060
TI  - Glucose buffer is suitable for blood group conversion with alpha-N
      acetylgalactosaminidase and alpha-galactosidase.
AB  - BACKGROUND: It is well known that the buffer plays a key role in the enzymatic
      reaction involved in blood group conversion. In previous study, we showed that a
      glycine buffer is suitable for A to O or B to O blood group conversion. In this
      study, we investigated the use of 5% glucose and other buffers for A to O or B to
      O blood group conversion by alpha-N-acetylgalactosaminidase or alpha
      galactosidase. MATERIALS AND METHODS: We compared the binding ability of alpha-N
      acetylgalactosaminidase/alpha-galactosidase with red blood cells (RBC) in
      different reaction buffers, such as normal saline, phosphate-buffered saline
      (PBS), a disodium hydrogen phosphate-based buffer (PCS), and 5% commercial
      glucose solution. The doses of enzymes necessary for the A/B to O conversion in
      different reaction buffers were determined and compared. The enzymes' ability to
      bind to RBC was evaluated by western blotting, and routine blood typing and
      fluorescence activated cell sorting was used to evaluate B/A to O conversion
      efficiency. RESULTS: The A to O conversion efficiency in glucose buffer was
      similar to that in glycine buffer with the same dose (>0.06 mg/mL pRBC). B to O
      conversion efficiency in glucose buffer was also similar to that in glycine
      buffer with the same dose (>0.005 mg/mL pRBC). Most enzymes could bind with RBC
      in glycine or glucose buffer, but few enzymes could bind with RBC in PBS, PCS, or
      normal saline. CONCLUSION: These results indicate that 5% glucose solution
      provides a suitable condition for enzymolysis, especially for enzymes combining
      with RBC. Meanwhile, the conversion efficiency of A/B to O was similar in glucose
      buffer and glycine buffer. Moreover, 5% glucose solution has been used for years
      in venous transfusion, it is safe for humans and its cost is lower. Our results
      do, therefore, suggest that 5% glucose solution could become a novel suitable
      buffer for A/B to O blood group conversion.

PMID- 24333061
TI  - A pilot study on screening blood donors with individual-donation nucleic acid
      testing in China.
AB  - BACKGROUND: Nucleic acid amplification testing (NAT) is not yet obligatory in
      China for blood donor screening and the risk of enzyme immunoassay (EIA)
      negative, NAT-reactive donations in Chinese blood donors has rarely been
      reported. The aim of this study was to screen a population of Chinese blood
      donors using a triplex individual-donation (ID)-NAT assay and assess the safety
      benefits of implementing NAT. MATERIALS AND METHODS: Between 1st August, 2010 and
      31st December, 2011 all donations at a Chinese blood centre were screened
      individually using the Procleix(r) Ultrio(r) assay, a multiplex NAT assay for the
      detection of hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human
      immunodeficiency virus-1 (HIV-1) RNA. All donations were also screened for HBsAg,
      anti-HIV and anti-HCV using two different EIA for each marker. Samples with
      discordant results between NAT and EIA were further tested with an alternative
      NAT assay (Cobas(r) TaqMan(r)). Potential yield cases (serologically negative/NAT
      reactive donors) were further evaluated when possible. RESULTS: During the study
      period a total of 178,447 donations were screened by NAT and EIA, among which 169
      HBV NAT yield cases (0.095%) were detected. No N AT yield cases were found for
      HIV-1 or HCV. For the HBV NAT yield cases, follow-up results showed that 11
      (6.51%) were probable or confirmed HBV window period infections, 5 (2.96%) were
      chronic HBV carriers and 153 (90.53%) were probable or confirmed occult HBV
      infections. There was a statistically significant difference between the NAT
      positive rates for first-time vs repeat donations (0.472% vs 0.146%,
      respectively; P<0.001). DISCUSSION: Our data demonstrate that the potential HBV
      yield rate was 1:1,056 for blood donations in the Zhejiang province of China.
      Implementation of NAT will provide a significant increment in safety relative to
      serological screening alone.

PMID- 24333062
TI  - Erythrocytapheresis compared with whole blood phlebotomy for the treatment of
      hereditary haemochromatosis.
AB  - BACKGROUND: Hereditary haemochromatosis may result in severe organ damage which
      can be prevented by therapy. We studied the possible advantages and disadvantages
      of erythrocytapheresis as compared with phlebotomy in patients with hereditary
      haemochromatosis. MATERIALS AND METHODS: In a prospective, randomised, open-label
      study, patients with hereditary haemochromatosis were randomised to bi-weekly
      apheresis or weekly whole blood phlebotomy. Primary end-points were decrease in
      ferritin levels and transferrin saturation. Secondary endpoints were decrease in
      haemoglobin levels, discomfort during the therapeutic procedure, costs and
      technicians' working time. RESULTS: Sixty-two patients were included. Thirty
      patients were randomised to apheresis and 32 to whole blood phlebotomy.
      Initially, ferritin levels declined more rapidly in the apheresis group, and the
      difference became statistically highly significant at 11 weeks; however, time to
      normalisation of ferritin level was equal in the two groups. We observed no
      significant differences in decline of transferrin saturation, haemoglobin levels
      or discomfort. The mean cumulative technician time consumption until the ferritin
      level reached 50 MUg/L was longer in the apheresis group, but the difference was
      not statistically significant. The cumulative costs for materials until
      achievement of the desired ferritin levels were three-fold higher in the
      apheresis group. CONCLUSION: Treatment of hereditary haemochromatosis with
      erythrocytapheresis instead of whole blood phlebotomy results in a more rapid
      initial decline in ferritin levels and a reduced number of procedures per
      patient, but not in earlier achievement of target ferritin level. The frequency
      of discomfort was equally low with the two methods. The costs and, probably,
      technician time consumption were higher in the apheresis group.

PMID- 24333064
TI  - Comments on "Glucose ameliorates the metabolic profile and mitochondrial function
      of platelet concentrates during storage in autologous plasma".

PMID- 24333063
TI  - Reply to: Comments on "Glucose ameliorates the metabolic profile and
      mitochondrial function of platelet concentrates during storage in autologous
      plasma".

PMID- 24333065
TI  - Comparison of in vitro responses to fresh whole blood and reconstituted whole
      blood after collagen stimulation.
AB  - BACKGROUND: In patients who have large bleeds, there is a tendency to transfuse
      more plasma and platelets than recommended in earlier guidelines, and accordingly
      many hospitals now provide "transfusion packages" with an intended red
      cell:platelet:plasma ratio of 1:1:1. The purpose of this study was to investigate
      in vitro functions of transfusion packs compared with fresh whole blood. MATERIAL
      AND METHODS: "Reconstituted whole blood" was prepared with the same ratio of red
      cells, platelets and plasma as used in local transfusion packages. The
      aggregation and thrombin-antithrombin complex formation responses to collagen
      stimulation of this reconstituted whole blood were compared with those of fresh
      whole blood. The storage time of red cells and platelets was varied in a
      systematic manner, giving nine different compositions of reconstituted whole
      blood that simulated transfusion packs. RESULTS: The responses varied
      significantly between whole blood and reconstituted whole blood -and between the
      reconstituted whole blood of different compositions. A significant decrease
      (p<0.005) in collagen-induced platelet count reduction was seen with increasing
      platelet and red blood cell age. Thrombin-antithrombin complex formation peaked
      in studies with platelets stored for 5 days. The red cells stored for the longest
      time induced the greatest thrombin-antithrombin complex formation. Fresh whole
      blood gives more consistent responses, and the aggregation response to collagen
      is stronger than in reconstituted whole blood. DISCUSSION: Our results indicate
      that in vitro responses of reconstituted whole blood vary substantially according
      to how long the red cells and platelets are stored for. As the responses obtained
      by testing whole blood are more consistent and usually stronger, the alternative
      use fresh whole blood in special conditions should not be excluded without
      further consideration.

PMID- 24333066
TI  - Thalassaemia intermedia: the role of erythroexchange in the treatment of an
      indolent wound.

PMID- 24333067
TI  - Blood and blood-associated symbols: some ethical and legal considerations.

PMID- 24333068
TI  - Blood and blood-associated symbols beyond medicine and transfusion: far more
      complex than first appears.

PMID- 24333069
TI  - Cross-match-compatible platelets improve corrected count increments in patients
      who are refractory to randomly selected platelets.
AB  - BACKGROUND: Cross-match-compatible platelets are used for the management of
      thrombocytopenic patients who are refractory to transfusions of randomly selected
      platelets. Data supporting the effectiveness of platelets that are compatible
      according to cross-matching with a modified antigen capture enzyme-linked
      immunosorbent assay (MAC-ELISA or MACE) are limited. This study aimed to
      determine the effectiveness of cross-match-compatible platelets in an unselected
      group of refractory patients. MATERIALS AND METHODS: One hundred ABO compatible
      single donor platelet transfusions given to 31 refractory patients were studied.
      Patients were defined to be refractory if their 24-hour corrected count increment
      (CCI) was <5*10(9)/L following two consecutive platelet transfusions. Platelets
      were cross-matched by MACE and the CCI was determined to monitor the
      effectiveness of platelet transfusions. RESULTS: The clinical sensitivity,
      specificity, positive predictive value and negative predictive value of the MACE
      cross-matched platelets for post-transfusion CCI were 88%, 54.6%, 39.3% and
      93.2%, respectively. The difference between adequate and inadequate post
      transfusion 24-hour CCI for MACE cross-matched-compatible vs incompatible single
      donor platelet transfusions was statistically significant (p=0.000). The 24-hour
      CCI (mean+/-SD) was significantly higher for cross-match-compatible platelets
      (9,250+/-026.6) than for incompatible ones (6,757.94+/-2,656.5) (p<0.0001). Most
      of the incompatible cross-matches (73.2%) were due to anti-HLA antibodies, alone
      (55.3% of cases) or together with anti-platelet glycoprotein antibodies (17.9%).
      DISCUSSION: The clinical sensitivity and negative predictive value of platelet
      cross-matching by MACE were high in this study and such tests may, therefore, be
      used to select compatible platelets for refractory patients. A high negative
      predictive value demonstrates the greater chance of an adequate response with
      cross-matched-compatible platelets.

PMID- 24333070
TI  - Spectrum of anti-M: a report of three unusual cases.

PMID- 24333071
TI  - Prevalence, specificity and risk of red blood cell alloantibodies among
      hospitalised Hubei Han Chinese patients.
AB  - BACKGROUND: The prevalence, specificity and risk of red blood cell alloantibodies
      vary widely among different geographic areas, races, and diseases and according
      to different methods of study, but no data are available on the Chinese Han
      population, who were investigated in the present study. MATERIALS AND METHODS:
      Antibody screening was conducted among 42,517 hospitalised Hubei Han Chinese
      individuals using column agglutination technology. Samples that were positive in
      antibody screening were subjected to antibody identification by the tube test.
      Clinical data, including gender, age, race, transfusion history and records of
      alloantibody detection, transfusion reactions or haemolytic disease of the
      newborn, were collected to analyse the prevalence and specificity of
      alloantibodies and complications associated with them. RESULTS: A total of 212
      patients with alloantibodies were identified among 42,517 patients, yielding a
      prevalence of 0.50% in this study. Significantly different prevalence rates were
      observed according to age and sex. The most frequently identified alloantibodies
      were anti-E (87/212, 41.0%), anti-D (45/212, 21.2%), anti-M (41/212, 19.3%) and a
      combination of anti-E and anti-c (13/212, 6.1%). Haemolytic disease was observed
      in 13 infants with anti-D, three infants with anti-E and one infant with anti
      Fy(a) alloantibodies. Delayed haemolytic transfusion reactions occurred in four
      patients with alloantibodies. DISCUSSION: In hospitalised Hubei Han Chinese
      individuals, the overall prevalence of alloantibodies was 0.50%, with anti-E,
      anti-D and anti-M being the most frequently identified alloantibodies. These
      results indicate that anti-D and anti-E alloantibodies were major risk factors
      for haemolytic disease of the newborn or delayed haemolytic transfusion reactions
      in this study population.

PMID- 24333072
TI  - Hyperhaemolysis syndrome responsive to splenectomy in a patient with deltabeta
      thalassaemia: a discussion on underlying mechanisms.

PMID- 24333073
TI  - Comparison of quality of red blood cells made from whole blood (after 8 and 24
      hours holding time at 2-6  degrees C and 20-24  degrees C) in Iran.

PMID- 24333074
TI  - A calcium-containing electrolyte-balanced hydroxyethyl starch (HES) solution is
      associated with higher factor VIII activity than is a non-balanced HES solution,
      but does not affect von Willebrand factor function or thromboelastometric
      measurements--results of a model of in vitro haemodilution.
AB  - BACKGROUND: Hydroxyethyl starch (HES) is known to impair blood coagulation. The
      impact of calcium-containing, balanced carrier solutions of HES on coagulation is
      controversial. We investigated the effects of increasing degrees of haemodilution
      with modern 6%, electrolyte-balanced HES vs non-balanced HES on coagulation in
      vitro, and compared the balanced HES to a balanced crystalloid solution for an
      internal control. MATERIALS AND METHODS: Blood samples from ten healthy
      volunteers were diluted in vitro by 20%, 40% and 60% with either calcium
      containing balanced 130/0.42 HES, non-balanced 130/0.4 HES or balanced
      crystalloid. In all samples, blood counts, prothrombin time ratio, activated
      partial thromboplastin time, ionized calcium, factor VIII activity, von
      Willebrand factor antigen, von Willebrand factor collagen binding activity, and
      von Willebrand factor activity were determined, and activated rotational
      thromboelastometry (EXTEM and FIBTEM assays) was performed. RESULTS:
      Haemodilution impaired coagulation in a dilution-dependent manner as determined
      by both conventional laboratory assays and thromboelastometry. Ionized calcium
      increased with balanced HES (p<=0.004), but decreased with non-balanced HES
      (p<=0.004). Prothrombin time ratio (p<=0.002) and factor VIII levels (p=0.001)
      were better preserved with balanced HES than with non-balanced HES in dilutions
      >=40%. Thromboelastometry showed no differences between values in blood diluted
      with the balanced or non-balanced HES. DISCUSSION: In vitro, a balanced calcium
      containing carrier solution of 6% HES 130/0.42 preserved coagulation better than
      did non-balanced HES 130/0.4 as quantified by conventional coagulation assays,
      but not in activated thromboelastometry. One explanation could be the increased
      ionized calcium levels after dilution with calcium-containing carrier solutions.

PMID- 24333076
TI  - Low compliance of men having sex with men with self-deferral from blood donation
      in a Chinese population.
AB  - BACKGROUND: The prevalence of human immunodeficiency virus (HIV) in men having
      sex with men (MSM) is generally higher than that in the average adult male
      population. In Hong Kong a permanent deferral mechanism is in place to minimise
      viral transmission during the window period. As regards donor deferral, the
      attitudes and behaviours of MSM in the community are crucial to ensuring blood
      safety. MATERIALS AND METHODS: A web-based questionnaire was constructed in the
      Chinese language. Through online advertisement and the assistance of outreach
      workers, sexually active MSM were recruited to participate in the survey. The
      questionnaire was composed of items on: (i) demographics, (ii) history and
      frequency of blood donations, (iii) profile of sexual practice, and (iv) views on
      time-limited vs permanent deferral. RESULTS: Over a 6-week period in 2012, 250
      MSM, three-quarters of whom were aged between 16 and 30 years old, were
      recruited. Almost half (47.6%) gave a history of blood donation. The majority
      (75.6%) were repeat donors, one-third of whom gave blood every 3-6 months.
      Compared to non-donors, a higher proportion of blood donors had had anal sex and
      multiple partners in the preceding year, while their condom usage rate was
      similar. Current donors were inclined to agree with time-limited deferral. With
      the latter's implementation, the number of donors would increase, but the
      compliance rate might vary widely. DISCUSSION: Blood donation is common among MSM
      in Hong Kong. The risk of HIV transmission depends largely on their compliance
      with the deferral mechanism applied, irrespectively of whether it is permanent or
      time-limited.

PMID- 24333077
TI  - Atypical haemolytic-uraemic syndrome due to heterozygous mutations of CFH/CFHR1-3
      and complement factor H 479.

PMID- 24333075
TI  - CD144+ endothelial microparticles as a marker of endothelial injury in neonatal
      ABO blood group incompatibility.
AB  - BACKGROUND: ABO antigens are expressed on the surfaces of red blood cells and the
      vascular endothelium. We studied circulating endothelial microparticles (EMP) in
      ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial
      activation to test a hypothesis of possible endothelial injury in neonates with
      ABO HDN, and its relation with the occurrence and severity of haemolysis.
      MATERIAL AND METHODS: Forty-five neonates with ABO HDN were compared with 20
      neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy
      neonates with matched mother and infant blood groups (healthy controls).
      Laboratory investigations were done for markers of haemolysis and von Willebrand
      factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after
      therapy (exchange transfusion and/or phototherapy). RESULTS: vWF Ag and pre
      therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy
      controls, and were significantly higher in babies with ABO HDN than in those with
      Rh HDN (p<0.05). In ABO HDN, pre-therapy EMP levels were higher in patients with
      severe hyperbilirubinaemia than in those with mild and moderate disease or those
      with Rh HDN (p<0.001). Post-therapy EMP levels were lower than pre-therapy levels
      in both the ABO HDN and Rh HDN groups; however, the decline in EMP levels was
      particularly evident after exchange transfusion in ABO neonates with severe
      hyperbilirubinaemia (p<0.001). Multiple regression analysis revealed that the
      concentrations of haemoglobin, lactate dehydrogenase and indirect bilirubin were
      independently correlated with pre-therapy EMP levels in ABO HDN. DISCUSSION:
      Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury
      parallel to the IgG-mediated erythrocyte destruction and could serve as a
      surrogate marker of vascular dysfunction and disease severity in neonates with
      this condition.

PMID- 24333078
TI  - HELLP syndrome and its relation with the antiphospholipid syndrome.

PMID- 24333079
TI  - Estimation of the prevalence and rate of acute transfusion reactions occurring in
      Windhoek, Namibia.
AB  - BACKGROUND: Acute transfusion reactions are probably common in sub-Saharan
      Africa, but transfusion reaction surveillance systems have not been widely
      established. In 2008, the Blood Transfusion Service of Namibia implemented a
      national acute transfusion reaction surveillance system, but substantial under
      reporting was suspected. We estimated the actual prevalence and rate of acute
      transfusion reactions occurring in Windhoek, Namibia. METHODS: The percentage of
      transfusion events resulting in a reported acute transfusion reaction was
      calculated. Actual percentage and rates of acute transfusion reactions per 1,000
      transfused units were estimated by reviewing patients' records from six
      hospitals, which transfuse >99% of all blood in Windhoek. Patients' records for
      1,162 transfusion events occurring between 1(st) January - 31(st) December 2011
      were randomly selected. Clinical and demographic information were abstracted and
      Centers for Disease Control and Prevention National Healthcare Safety Network
      criteria were applied to categorize acute transfusion reactions. RESULTS: From
      January 1 - December 31, 2011, there were 3,697 transfusion events (involving
      10,338 blood units) in the selected hospitals. Eight (0.2%) acute transfusion
      reactions were reported to the surveillance system. Of the 1,162 transfusion
      events selected, medical records for 785 transfusion events were analysed, and 28
      acute transfusion reactions were detected, of which only one had also been
      reported to the surveillance system. An estimated 3.4% (95% confidence interval
      [CI]: 2.3-4.4) of transfusion events in Windhoek resulted in an acute transfusion
      reaction, with an estimated rate of 11.5 (95% CI: 7.6-14.5) acute transfusion
      reactions per 1,000 transfused units. CONCLUSION: The estimated actual rate of
      acute transfusion reactions is higher than the rate reported to the national
      haemovigilance system. Improved surveillance and interventions to reduce
      transfusion-related morbidity and mortality are required in Namibia.

PMID- 24333080
TI  - Two molecular polymorphisms to detect the (C)ce(s) type 1 haplotype.

PMID- 24333081
TI  - The processing of stem cell concentrates from the bone marrow in ABO-incompatible
      transplants: how and when.

PMID- 24333082
TI  - Analysis of density and epitopes of D antigen on the surface of erythrocytes from
      DEL phenotypic individuals carrying the RHD1227A allele.
AB  - BACKGROUND: The characteristics of the D antigen are important as they influence
      the immunogenicity of D variant cells. Several studies on antigenic sites have
      been reported in normal D positive, weak D and partial D cases, including a
      comprehensive analysis of DEL types in Caucasians. The aim of this study was to
      assess D antigen density and epitopes on the erythrocyte surface of Asian type
      DEL phenotypic individuals carrying the RHD1227A allele in the Chinese
      population. MATERIALS AND METHODS: A total of 154 DEL phenotypic individuals
      carrying the RHD1227A allele were identified through adsorption and elution tests
      and polymerase chain reaction analysis with sequence-specific primers in the
      Chinese population. D antigen density on the erythrocyte surface of these
      individuals was detected using a flow cytometric method. An erythrocyte sample
      with known D antigen density was used as a standard. Blood samples from D
      negative and D-positive individuals were used as controls. In addition, D antigen
      epitopes on the erythrocyte surface of DEL individuals carrying the RHD1227A
      allele were investigated with 18 monoclonal anti-D antibodies specific for
      different D antigen epitopes. RESULTS: The means of the median fluorescence
      intensity of D antigen on the erythrocyte membrane surface of D-negative, D
      positive and DEL individuals were 2.14+/-0.25, 193.61+/-11.43 and 2.45+/-0.82,
      respectively. The DEL samples were estimated to have approximately 22 D antigens
      per cell. The samples from all 154 DEL individuals reacted positively with 18
      monoclonal anti-D antibodies specific for different D antigen epitopes.
      DISCUSSION: In this study, D antigen density on the erythrocyte surface of DEL
      individuals carrying the RHD1227A allele was extremely low, there being only very
      few antigenic molecules per cell, but the D antigen epitopes were grossly
      complete.

PMID- 24333083
TI  - In vitro evaluation of clot quality and stability in a model of severe
      thrombocytopenia: effect of fibrinogen, factor XIII and thrombin-activatable
      fibrinolysis inhibitor.
AB  - BACKGROUND: The treatment options in severe thrombocytopenia (platelet count
      <=20*10(9)/L) are limited. The aim of this study was to investigate ways of
      improving blood clotting and stability in reconstituted thrombocytopenia.
      MATERIALS AND METHODS: Thrombocytopenia (platelets [16+/-4]*10(9)/L) was created
      by differential centrifugation of normal blood followed by reconstitution of
      whole blood which was subjected to clotting in a rotation thromboelastometer by
      CaCl2 and tissue factor, and to fibrinolysis by tissue plasminogen activator
      (tPA). In separate experiments, blood was diluted by 40% with TRIS/saline
      solution. Blood was treated with fibrinogen (fib), factor XIII (FXIII), and
      thrombin-activatable fibrinolysis inhibitor (TAFI). RESULTS: The maximum clot
      firmness of thrombocytopenic blood was approximately 2-fold less than that of
      intact blood. Supplementation of blood with fib and FXIII improved clot
      formation. In the presence of tPA, among fib, FXIII and TAFI, only fib stimulated
      clot propagation whereas each of these agents increased clot strength. There was
      a synergistic effect when fib was added together with FXIII or TAFI. Fibrinolysis
      was inhibited by TAFI and to a greater extent by TAFI + FXIII. Fourty percent
      dilution of blood reduced clot strength and increased susceptibility to tPA. Clot
      strength was increased by the treatments in the following order: fib/FXIII/TAFI >
      fib/TAFI > fib > TAFI > FXIII. In the presence of tPA, TAFI and FXIII lysed the
      clots significantly more slowly. This effect was stronger when blood was treated
      with the combination of fib/FXIII/TAFI. Doubling the fib concentration, alone or
      together with other agents, did not improve clot strength or stability.
      DISCUSSION: Augmentation of clot formation and anti-fibrinolysis by combining
      fib, FXIII and TAFI may be beneficial for the treatment of patients with severe
      thrombocytopenia especially when complicated by haemodilution following
      introduction of fluids to compensate for massive blood loss.

PMID- 24333084
TI  - The influence of storage age on iron status, oxidative stress and antioxidant
      protection in paediatric packed cell units.
AB  - BACKGROUND: Receipt of blood transfusions is associated with the major
      consequences of prematurity such as bronchopulmonary dysplasia. Transfusion
      mediated (iron-induced) oxidative damage, coupled with the limited ability of the
      premature baby to deal with enhanced iron and oxidative load may contribute to
      this. Adverse effects of transfusion may be related to duration of storage. This
      study examined the influence of storage on iron and oxidative status in
      paediatric packed red blood cell units. MATERIALS AND METHODS: Paediatric packed
      red blood cell units were sampled 3 days post-donation, then at 7 days and weekly
      until day 35. The extracellular medium was separated and the following measured:
      total iron concentration, total iron binding capacity, non-transferrin-bound
      iron, haemoglobin, total and reduced ascorbate, glutathione and malondialdehyde.
      RESULTS: Measurable total and non-transferrin bound iron were present in the
      extracellular fluid of paediatric packs on day 3. Both parameters rose almost
      linearly to maximal values at 35 days. Haemoglobin and malondialdehyde levels
      rose gradually from day 3 to day 21, then more steeply to day 35. Ascorbate
      existed mainly in the oxidised form and fell rapidly towards the end of storage.
      Intracellular GSH fell throughout the period of storage. Strong correlations
      existed between biomarkers of oxidative damage and iron parameters. DISCUSSION:
      These data suggest that iron released following the initial preparation of packed
      red blood cell units may derive from free radical-mediated oxidative damage to
      the red blood cells and haemoglobin, rather than from extracellular haemoglobin.
      Iron continues to be released during storage as antioxidant protection declines.
      A cycle of free radical-mediated damage may initiate and then further exacerbate
      iron release during storage which, in turn, may mediate further free radical
      mediated cellular damage. The potential consequences to recipients of older
      stored blood may be significant.

PMID- 24333085
TI  - The risk of transfusion-transmitted viral infections at the Gabonese National
      Blood Transfusion Centre.
AB  - BACKGROUND: Blood transfusions carry the risk of transmitting blood-borne
      infections. In contrast to the situation in the developed world, there is a
      limited number of studies examining this problem in sub-Saharan Africa. In this
      study we aimed to calculate the risks of acquiring human immunodeficiency virus
      (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection from units
      of blood issued by the Gabonese Blood Transfusion Centre between 2009 and 2011.
      MATERIALS AND METHODS: All the donations were tested for infectious diseases and
      the seroconversion incidence rates of HIV, HBV and HCV were calculated. The
      residual risk of transfusion-associated transmission for each virus was
      calculated by multiplying the seroconversion rates by the window period expressed
      in fractions of a year. RESULTS: The risks of becoming infected with HIV, HCV,
      and HBV in subjects receiving units of blood from the Gabonese Blood Transfusion
      Centre were 64.7, 207.94 and 534.53 per million donations, respectively.
      CONCLUSIONS: This study, which is the first to quantify the true risks of
      transfusion-transmitted infections in Gabon, reveals and confirms the need to
      reinforce preventative and screening strategies to improve transfusion safety in
      sub-Saharan Africa.

PMID- 24333086
TI  - The effects of pneumatic tube transport on fresh and stored platelets in additive
      solution.
AB  - BACKGROUND: Limited scientific work has been conducted on potential in vitro
      effects of transport on pneumatic tube systems on blood components, in particular
      platelets. MATERIALS AND METHODS: To evaluate the possible effects of the
      Swisslog TranspoNet system on the cellular, metabolic, phenotypic and secreting
      properties of fresh and stored platelets, we set up a four-arm paired study
      comparing transported and non-transported platelets. Platelets were aliquoted,
      prepared with the OrbiSac system and suspended in 70% SSP+ (n=8). All in vitro
      parameters were monitored over a 7-day storage period. RESULTS: Throughout
      storage, no differences were observed in glucose consumption, lactate production,
      pH, pCO2, ATP, hypotonic shock response reactivity, CD62P, PAC-1, platelet
      endothelial cell adhesion molecule-1 or CD42b. The release of sCD40L increased
      (p<0.01) in all units but without any significant differences between groups.
      CONCLUSION: The storage stability of all platelets conveyed by the Swisslog
      TranspoNet system was not impaired throughout 7 days of storage. The Swisslog
      TranspoNet system does not, therefore, seem to be a risk for increased metabolic
      activity, activation or release reactions from the platelets. This lack of effect
      of the pneumatic tube transport system did not seem to be affected by the age of
      the platelets or repeated transport.

PMID- 24333087
TI  - Single-donor platelet apheresis: observational comparison of the new Haemonetics
      Universal Platelet protocol with the previous Concentrated Single Donor Platelet
      protocol.
AB  - BACKGROUND: The Haemonetics MCS((r))+ cell separator is a device dedicated to the
      collection of leucoreduced single-donor platelets. The new Universal Platelet
      protocol has been introduced to improve the efficiency of apheresis and increase
      flexibility in the collection of leucoreduced platelets in combination with red
      blood cells and plasma. In this study we compared its performance with that of
      the previous Concentrated Single Donor Platelet protocol. MATERIALS AND METHODS:
      This observational study had a within-subject design and involved 135 donors who
      underwent plateletapheresis with both protocols. The primary end-point was
      collection efficiency; secondary end-points were other performance indices, such
      as procedure time and collection rate. A satisfaction questionnaire was also
      administered to the 135 donors to evaluate opinions on duration, comfort and side
      effects of donations with the two protocols. For each parameter of interest, we
      tested the difference between the two protocols within donors, using a one-sample
      t-test or exact McNemar's test as appropriate. RESULTS: The collection efficiency
      of the Universal Platelet protocol was significantly higher than that of the
      Concentrated Single Donor Platelet protocol (58% vs 47%; p<0.0001). The Universal
      Platelet Protocol collected more platelets in less time, leading to a higher
      collection rate (6.5 vs 5.0*10(9)/min; p<0.0001). In general, donors found
      apheresis with the Universal Platelet protocol of equal duration or faster, of
      similar or greater comfort and with an equal number or fewer side effects,
      compared with the Concentrated Single Donor Platelet protocol. DISCUSSION: Our
      study endorses the use of the new Universal Platelet protocol in daily
      transfusion practice since it substantially improves collection efficiency in
      leucoreduced platelet procedures compared with the Concentrated Single Donor
      Platelet protocol. This technical improvement seems to be accompanied by equal or
      greater comfort for the donor.

PMID- 24333088
TI  - A comprehensive investigation of RHD polymorphisms in the Chinese Han population
      in Xi'an.
AB  - BACKGROUND: This study is a comprehensive analysis of RHD in D-negative
      phenotypes in saline, in Xi'an, Shanxi province, central China. MATERIAL AND
      METHODS: DCcEe in saline was measured for each blood sample from every donor
      between January 2008 and June 2012 in the Xi'an Blood Centre, China. D-negative
      results were confirmed by an indirect antiglobulin test and further investigated
      by adsorption-elution as required. The initial step of molecular analysis was RHD
      zygosity testing. Then RHD was detected by a sequence-specific polymerase chain
      reaction system for RHD(1227G>A), weak D type 15, and RHD(711delC) alleles for
      the samples carrying at least one RHD. For the remaining non-identified samples,
      ten RHD exons were amplified using a previously widely used RHD coding region
      sequencing method. Some RHD/RHCE conversion alleles were identified while those
      remaining were submitted to direct sequencing. RESULTS: Overall, 2,493 D-negative
      samples in saline were detected in a total of 890,403 donors (D-negative rate,
      0.28%). Among the D-negative individuals, RHD deletion (d/d) was assessed in 1685
      donors (67.59%). Non-functional RHD alleles were detected in 184 donors (7.38%),
      the most common being the RHD-CE(2-9)-RHD and RHD(711delC) alleles. Two new
      alleles were observed and family investigations were performed; RHD(1227G>A) DEL
      was detected in 516 individuals (20.70%), and weak D or partial D variants were
      identified in 108 donors (4.33%). The most common alleles were weak D type 15,
      D(VI) type 3 and D(V) type 2. Four new weak D alleles were noted, and two cases
      of RHD(1227G>A)/weak D type 15 heterozygosity were confirmed. CONCLUSIONS:
      Currently, it seems to be difficult to observe any new RHD alleles in the Han
      Chinese population. D prediction in this population is easier because popular
      alleles are dominant, accounting for about 99.80% of alleles in D-negative
      people. Weak D types and partial D variants are rare and occur in approximately
      0.01% of the population.

PMID- 24333089
TI  - (C)ce(s) haplotype screening in Tunisian blood donors.
AB  - BACKGROUND: The (C)ce(s) haplotype, mainly found in black individuals, contains
      two altered genes: a hybrid RHD-CE-D(s) gene segregated with a ce(s) allele of
      RHCE with two single nucleotide polymorphisms, c. 733C>G (p.Leu245Val) in exon 5
      and c. 1006G>T (Gly336Cys) in exon 7. This haplotype could be responsible for
      false positive genotyping results in RhD-negative individuals and at a homozygous
      level lead to the loss of a high incidence antigen RH34. The aim of this study
      was to screen for the (C)ce(s) haplotype in Tunisian blood donors, given its
      clinico-biological importance. MATERIAL AND METHODS: Blood samples were randomly
      collected from blood donors in the blood transfusion centre of Sousse (Tunisia).
      A total of 356 RhD-positive and 44 RhD-negative samples were tested for the
      (C)ce(s) haplotype using two allele-specific primer polymerase chain reactions
      that detect c. 733C>G (p.Leu245Val) and c. 1006G>T (p. Gly336Cys) substitutions
      in exon 5 and 7 of the RHCE gene. In addition, the presence of the D-CE hybrid
      exon 3 was evaluated using a sequence-specific primer polymerase chain reaction.
      RESULTS: Among the 400 individuals only five exhibited the (C)ce(s) haplotype in
      heterozygosity, for a frequency of 0.625%. On the basis of the allele-specific
      primer polymerase chain reaction results, the difference in (C)ce(s) haplotype
      frequency was not statistically significant between RhD-positive and RhD-negative
      blood donors. DISCUSSION: These data showed the presence of the (C)ce(s)
      haplotype at a low frequency (0.625%) compared to that among Africans in whom it
      is common. Nevertheless, the presence of RHD-CE-D(s) in Tunisians, even at a
      lower frequency, should be considered in the development of a molecular
      genotyping strategy for Rh genes, to ensure better management of the prevention
      of alloimmunisation.

PMID- 24333090
TI  - Investigating the influence of age, gender and ABO blood group on ADAMTS-13
      antigen and activity levels in healthy Arabs.

PMID- 24333091
TI  - Double bull's eye for post-operative intravenous iron in patient blood
      management: better outcome and cost-effective.

PMID- 24333093
TI  - Barriers to the use of morphine for the management of severe postoperative pain -
      a before and after study.
AB  - AIM: To reduce the number of patients experiencing severe postoperative pain by
      prescribing 10 mg Morphine either as oral solution or by IM injection as an
      alternative to Tramadol Hydrochloride in an analgesic protocol. MATERIALS AND
      METHODS: Patients who received in-patient oral and maxillofacial surgery under
      general anaesthesia were included. Complex intervention analgesic protocols were
      developed including staff education, patient educations and analgesic protocols.
      80 patients were treated under the original protocol (tramadol hydrochloride for
      pain unmanaged by other drugs in protocol) over 4 months. 75 patients were
      treated under the second protocol (oral or intravenous morphine for pain
      unmanaged by other drugs in protocol). Patient perceptions to their pain
      management were then assessed. RESULTS: Proportion of patients reporting 'no
      pain' increased from 5% of 80 patients to 28% of 75 patients (p < 0.001). Report
      of severe pain reduced from 37% to 31% and not significant. Pain duration reduced
      from 18% to 12% for 75-100% time from surgery to discharge and not significant.
      Staff used protocols for 96% patients. Nurses provided patient information
      leaflets for 85%-80% patients. Nearly all patients (96% and 95%) reported overall
      satisfaction with their pain management. CONCLUSIONS: The use of morphine given
      orally or my IM injection rather than tramadol was associated with a significant
      increase in the number of patients reporting 'no pain'. However the number of
      patients experiencing severe pain was not significantly reduced. Despite this,
      most patients reported high levels of satisfaction which suggested that
      satisfaction questionnaires should not be used in isolation. Most patients
      received morphine orally rather than by IM injection but the oral dose may not
      have been high enough in this study.

PMID- 24333092
TI  - Key issues in inhibitor management in patients with haemophilia.

PMID- 24333094
TI  - CryoEM and image sorting for flexible protein/DNA complexes.
AB  - Intrinsically disordered regions of proteins and conformational flexibility
      within complexes can be critical for biological function. However, disorder,
      flexibility, and heterogeneity often hinder structural analyses. CryoEM and
      single particle image processing techniques offer the possibility of imaging
      samples with significant flexibility. Division of particle images into more
      homogenous subsets after data acquisition can help compensate for heterogeneity
      within the sample. We present the utility of an eigenimage sorting analysis for
      examining two protein/DNA complexes with significant conformational flexibility
      and heterogeneity. These complexes are integral to the non-homologous end joining
      pathway, and are involved in the repair of double strand breaks of DNA. Both
      complexes include the DNA-dependent protein kinase catalytic subunit (DNA-PKcs)
      and biotinylated DNA with bound streptavidin, with one complex containing the Ku
      heterodimer. Initial 3D reconstructions of the two DNA-PKcs complexes resembled a
      cryoEM structure of uncomplexed DNA-PKcs without additional density clearly
      attributable to the remaining components. Application of eigenimage sorting
      allowed division of the DNA-PKcs complex datasets into more homogeneous subsets.
      This led to visualization of density near the base of the DNA-PKcs that can be
      attributed to DNA, streptavidin, and Ku. However, comparison of projections of
      the subset structures with 2D class averages indicated that a significant level
      of heterogeneity remained within each subset. In summary, image sorting methods
      allowed visualization of extra density near the base of DNA-PKcs, suggesting that
      DNA binds in the vicinity of the base of the molecule and potentially to a
      flexible region of DNA-PKcs. 

PMID- 24333095
TI  - New radiotherapy approaches in locally advanced non-small cell lung cancer.
AB  - Radiotherapy plays a major role in the treatment of patients with locally
      advanced non-small cell lung cancer (NSCLC), particularly since most patients are
      not suitable for surgery due to the extent of their disease, advanced age and
      multiple co-morbidities. Despite advances in local and systemic therapies local
      control and survival remain poor and there is a sense that a therapeutic plateau
      has been reached with conventional approaches. Strategies for the intensification
      of radiotherapy such as dose escalation have shown encouraging results in phase I
      II trials, but the outcome of the phase III Radiation Therapy Oncology Group 0617
      trial was surprisingly disappointing. Hyperfractionated and/or accelerated
      fractionating schedules have demonstrated superior survival compared to
      conventional fractionation at the expense of greater oesophageal toxicity. Modern
      radiotherapy techniques such as the integration of 4-dimensional computed
      tomography for planning, intensity modulated radiotherapy and image-guided
      radiotherapy have substantially enhanced the accuracy of the radiotherapy
      delivery through improved target conformality and incorporation of tumour
      respiratory motion. A number of studies are evaluating personalised radiation
      treatment including the concept of isotoxic radiotherapy and the boosting of the
      primary tumour based on functional imaging. Proton beam therapy is currently
      under investigation in locally advanced NSCLC. These approaches, either alone or
      in combination could potentially allow for further dose escalation and
      improvement of the therapeutic ratio and survival for patients with NSCLC. 

PMID- 24333096
TI  - Immunology of cancer stem cells in solid tumours. A review.
AB  - Cancer stem cells (CSCs) represent a minor subpopulation of tumour cells that
      share some features with the normal stem cells of the tissue from which tumour
      derives and have the properties of self-renewal, multiple differentiation and
      tumour initiation (tumour-initiating cells, TICs). Thus CSCs/TICs need to survive
      cancer therapies in order to provide new, more differentiated, metastatic-prone
      tumour cells. This occurs through different signals delivered within the tumour
      microenvironment. The immune system of cancer patients may recognise CSCs/TICs
      and kill them though it is unclear whether this may occur in vivo during
      spontaneous tumour growth. This review summarises findings on the immunological
      profile of CSCs/TICs as compared with neoplastic non-stem cells and discusses the
      possible antigens recognised by the patients' immune system, the in vitro and the
      potential in vivo immunogenicity of such antigens and the ability of human
      CSCs/TICs to down-regulate the immune response by the release of a variety of
      suppressive factors. We conclude that available data on immunological
      characterisation of CSCs/TICs may be useful in the perspective of designing new
      translational immunotherapy protocols targeting CSCs/TICs. 

PMID- 24333097
TI  - A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for
      neuroblastoma.
AB  - The optimal use and effectiveness of (131)I-meta iodobenzylguanidine ((131)I
      mIBG) molecular radiotherapy for neuroblastoma remain unclear despite extensive
      clinical experience. This systematic review aimed to improve understanding of the
      current data and define uncertainties for future clinical trials. Bibliographic
      databases were searched for neuroblastoma and (131)I-mIBG. Clinical trials and
      non-comparative case series of (131)I-mIBG therapy for neuroblastoma were
      included. Two reviewers assessed papers for inclusion using the title and
      abstract with consensus achieved by discussion. Data were extracted by one
      reviewer and checked by a second. Studies with multiple publications were
      reported as a single study. The searches yielded 1216 citations, of which 51
      publications reporting 30 studies met our inclusion criteria. No randomised
      controlled trials (RCTs) were identified. In two studies (131)I-mIBG had been
      used as induction therapy and in one study it had been used as consolidation
      therapy. Twenty-seven studies for relapsed and refractory disease were
      identified. Publication dates ranged from 1987 to 2012. Total number of patients
      was 1121 with study sizes ranging from 10 to 164. There was a large amount of
      heterogeneity between the studies with regard to patient population, treatment
      schedule and response assessment. Study quality was highly variable. The
      objective tumour response rate reported in 25 studies ranged from 0% to 75%, mean
      32%. We conclude that (131)I-mIBG is an active treatment for neuroblastoma, but
      its place in the management of neuroblastoma remains unclear. Prospective
      randomised trials are essential to strengthen the evidence base. 

PMID- 24333098
TI  - ALDH2 Glu504Lys polymorphism and susceptibility to coronary artery disease and
      myocardial infarction in East Asians: a meta-analysis.
AB  - BACKGROUND AND AIMS: Emerging evidences have shown that the Glu504Lys variant in
      ALDH2 gene may greatly reduce the ability of ALDH2 to metabolize acetaldehyde,
      which could increase the risk of coronary artery disease (CAD) and myocardial
      infarction (MI). However, the reported results are still conflicting. To
      investigate the association between ALDH2 Glu504Lys polymorphism and the risk of
      CAD and MI in Asians, we analyzed all available studies in a meta-analysis.
      METHODS: A literature search of PubMed, Embase, Web of Science and Chinese
      BioMedical (CBM) databases was conducted for articles published before March 1,
      2013. The principal outcome measure was the crude odds ratios (ORs) with their
      corresponding confidence intervals (95% CIs) for evaluating the strength of the
      association. RESULTS: Meta-analysis showed that carriers of ALDH2 504lys allele
      were associated with increased risks of both CAD and MI (CAD: OR = 1.28, 95% CI:
      1.10-1.48, p = 0.001; MI: OR = 1.58, 95% CI: 1.15-2.19, p = 0.005). Subgroup
      analysis by country showed significant correlations between mutant genotypes
      (Glu/Lys + Lys/Lys) and increased risk to MI among Chinese and Korean populations
      (Chinese: OR = 1.89, 95% CI: 1.16-3.09, p = 0.011; Korean: OR = 1.69, 95%CI: 1.12
      2.55, p = 0.013), whereas similar associations were not observed among Japanese
      populations. CONCLUSIONS: The current meta-analysis provides strong evidence that
      ALDH2 Glu504Lys polymorphism may be associated with increased risk of CAD and MI
      in East Asians, especially among Chinese and Korean populations. However, more
      detailed and well-designed studies are still warranted to confirm these findings.

PMID- 24333099
TI  - The Connexin37 gene C1019T polymorphism and risk of coronary artery disease: a
      meta-analysis.
AB  - BACKGROUND AND AIMS: Mounting data have emerged suggesting that the Connexin37
      C1019T polymorphism increases susceptibility to coronary artery disease (CAD).
      However, previous studies yielded conflicting results. In the current study, a
      comprehensive meta-analysis was performed to investigate whether the C1019T
      polymorphism is associated with CAD risk. METHODS: A total of 11 studies
      examining the C1019T polymorphism and CAD were identified using MEDLINE, Embase,
      CNKI, Wanfang and CBM, in which 5535 CAD patients and 5626 controls were
      analyzed. A random-effects model was used to calculate odd ratios and confidence
      intervals, while addressing between-study heterogeneity. Publication bias was
      weighed using the Egger's test, Begg-Mazemdar test and funnel plot. RESULTS: In
      genetic models with striking heterogeneity, the risk of CAD was not associated
      with the C1019T polymorphism (allele comparison: p = 0.34, OR = 1.11, 95% CI 0.90
      1.36). Stratification by disease endpoints indicated that the 1019T allele was
      significantly associated with myocardial infarction (MI) (allele comparison: p
      <0.001, OR = 1.59, 95% CI 1.24-2.03). Further meta-regression analysis indicated
      that a large proportion of heterogeneity was probably due to the varying
      proportions of diabetes mellitus (DM) across studies (p = 0.014). CONCLUSIONS:
      Our results indicated that the C1019T polymorphism may be a moderate risk factor
      for MI and that DM was likely a potential source of between-study heterogeneity.

PMID- 24333100
TI  - Translational research in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma is well known to be a viral driven malignancy. Despite
      high loco-regional control rate with modern radiotherapy, distant metastasis
      remains as a major threat to the patients highlighting the importance of
      effective systemic therapy. Recent advances in the understanding of tumor
      biology, host cell-virus interaction and genetics have paved new ways for
      targeted therapies. This review summarizes the recent advances into our knowledge
      and understanding of NPC and highlights potential novel therapeutic strategies
      that may prove useful to treat this disease. 

PMID- 24333101
TI  - [Tick-borne relapsing fever in a rural area of southern Spain].
AB  - INTRODUCTION: Tick-borne relapsing fever (TBRF) is a zoonotic disease caused by
      spirochetes of the genus Borrelia. This disease is underdiagnosed in our area due
      to a low index of suspicion among clinicians, as well as its difficult diagnosis.
      This study aims to present our experience in the diagnosis and therapeutic
      management of TBRF and a literature review. METHODS: A retrospective medical
      chart review was carried out on children diagnosed of TBRF from 2002 to 2012 in
      our hospital, and included clinical, epidemiological, microbiological, treatment,
      and outcome data. RESULTS: Nine children with TBRF were identified. Median age
      was 11 years. All cases occurred during warm months. The most frequent presenting
      clinical findings were fever, chills, headache, vomiting, myalgia and abdominal
      pain. Meningeal involvement was identified in 2 cases. In the case of 2 patients,
      Borrelia infection was identified in several relatives at the time of diagnosis.
      Mean C-protein reactive was 187 mg/L, and low platelet counts were observed in
      56% of the cases. Borreliaspp. was visualized in peripheral blood smears in 67%
      of cases. All of the patients received antibiotic treatment. Doxycycline was used
      in children older than 8 years and erythromycin and penicillin in the younger
      ones. Jarisch-Herxheiner reaction occurred in one patient. All cases resolved
      without sequelae. CONCLUSIONS: We emphasize the importance of maintaining a high
      level of suspicion in endemic regions of TBRF. Early diagnosis and a correct
      therapy can prevent the appearance of subsequent fever recurrences and potential
      complications.

PMID- 24333102
TI  - [Evaluation of the transition from pediatric to adult diabetic unit for
      adolescents with type 1 diabetes].
AB  - INTRODUCTION: The transition between pediatric and adult care for young people
      with type 1 diabetes (T1D) is often poorly managed, with adverse consequences for
      health, as well as a decrease in the follow-up. OBJECTIVE: To analyze the
      metabolic control and the degree of satisfaction in a group of patients with T1D
      after being transferred from the Pediatric Diabetes Unit (PDU) to Adult Diabetes
      Unit (ADU). PATIENTS AND METHODS: Retrospective study in a cohort of 49 patients
      (43% female) with T1D. The age at diagnosis and transfer to ADU, time of onset of
      the disease, metabolic control (HbA1c), presence of diabetic complications and
      characteristics of medical follow-up were analysed using the statistics program:
      SPSS, version 17.0. RESULTS: Mean age at diagnosis 8.3+/-4.6 years and transfer
      to ADU 19.2+/-1.8 years. Mean time since onset of T1D in pediatrics, adults and
      overall: 10.8+/-5.0, 4.1+/-2.6 and 15.0+/-5.7 years, respectively. The 6% of
      adult patients were not being medically tracked. Among adults, 25% did not
      provide data about chronic complications, and 6% did not know their last HbA1c.
      The metabolic control after their transfer to the ADU worsened in 52% of the
      patients (HbA1c +0.79+/-0.70%). No correlation was found between the time since
      onset and the HbA1c value. Degree of satisfaction was either good or very good in
      96% of patients in the PDU and 74% in ADU. CONCLUSION: Better planning for the
      transfer of pediatric patients with T1D to ADU is highly recommended, in order to
      avoid deterioration of control and/or loss of follow-up.

PMID- 24333103
TI  - A comprehensive review of autoantibodies in primary Sjogren's syndrome: clinical
      phenotypes and regulatory mechanisms.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disease characterized by
      periepithelial lymphocytic infiltrates in affected tissues and the production of
      plethora of autoantibodies. Among them autoimmune responses against Ro/SSA and
      La/SSB are of major importance since their detection is routinely used for
      disease diagnosis and clinical characterization. Although the exact mechanisms
      underlying disease pathogenesis are not fully understood, the important role of
      salivary gland epithelial cells (SGEC) in the initiation and development of the
      local immune responses is well-established. SGECs are also capable to mediate the
      exposure of the Ro/SSA and La/SSB autoantigens to the immune system by elevated
      apoptosis and autoantigen release in apoptotic bodies and/or by the secretion of
      autoantigen-containing exosomes. The expression of these autoantigens in
      epithelial cells appears to be tightly regulated. Up-to-date, signaling of
      certain innate immunity receptors, such as TLR3, appear to be implicated in the
      regulation of Ro/SSA and La/SSB expression by SGECs, whereas the deregulated
      expression of certain miRNAs that are predicted to target them in SS patients
      suggests a regulatory feedback at the post-transcriptional level. In the
      periphery, the humoral autoimmune responses are further regulated by the
      development of an active network of idiotypic-antiidiotypic antibodies. The
      plethora of mechanisms suggests that autoimmune humoral responses in SS are
      tightly regulated. In this review, the major humoral autoimmune responses, recent
      advances on the role of epithelial cells in their development, as well as
      possible regulatory mechanisms will be discussed. 

PMID- 24333104
TI  - Testosterone is related to deviance in male army veterans, but relationships are
      not moderated by cortisol.
AB  - The Vietnam Experience Study (VES) of 4462 male U.S. Army veterans is the first
      large dataset used to demonstrate that testosterone (but not cortisol) is
      correlated with diverse measures of antisocial, aggressive or dominant behavior.
      Many subsequent studies have sustained these relationships while also pointing to
      important caveats. Some researchers suggest that testosterone is correlated to
      dominance and aggression only (or mostly) in people with low cortisol, not in
      those with high cortisol. Here we look back to the VES to test this "dual
      hormone" hypothesis. We find no testosterone-cortisol interaction for seven
      measures of antisocial deviance. We consider scope conditions under which the
      dual hormone hypothesis may be valid. 

PMID- 24333105
TI  - Icaritin attenuates cigarette smoke-mediated oxidative stress in human lung
      epithelial cells via activation of PI3K-AKT and Nrf2 signaling.
AB  - Icariin is the major active ingredient of Herba Epimedii. Icaritin (ICT) is a
      hydrolytic product of Icariin. In the present study, we investigated the
      protective role of ICT against cigarette smoke extract (CSE)-mediated oxidative
      stress in human lung epithelial A549 cells. As demonstrated by the WST-8 assay,
      exposure to CSE (2.5%, 5%, and 10%) reduced the cell viability of A549 cells
      (84%, 64% and 53%) in a dose-dependent manner and treatment with ICT 10 MUM
      dramatically attenuated CSE induced cytotoxicity (73% and 64%). The MFI data
      suggested that CSE induced oxidative stress by generating ROS (230) and 10 MUM
      ICT treatment attenuated CSE-induced ROS production (90). 10 MUM ICT treatment
      resulted in significant AKT activation, Nrf2 nuclear translocation, increased GCL
      transcription and GSH levels, as compared with CSE exposure alone. However, ICT
      mediated upregulation of GCL transcription in CSE-treated cells were lost in Nrf2
      siRNA-transfected cells. Furthermore, inhibition of PI3K/AKT signaling by
      LY294002 partially prevents ICT-induced nuclear translocation of Nrf2 and GCL
      transcription. These findings suggest that ICT attenuates CS-induced oxidative
      stress by quenching ROS and also by upregulating GSH via a PI3K-AKT-Nrf2
      dependent mechanism. Further studies are required to confirm that a similar
      protective effect of ICT occurs in the lungs in vivo in response to CS exposure.

PMID- 24333106
TI  - An unusual abdominal cystic mass in the round ligament of the uterus: a case
      report.
AB  - BACKGROUND: Cystic tumor of the round ligament is extremely rare. To our
      knowledge, this is the first case reported in the literature of a round ligament
      giant serous cystadenoma. CASE: A 17-year-old adolescent who presented with
      massive abdominal swelling and was later identified as a serous cystadenomas of
      the round ligament with a size of approximately 50 cm. A multidisciplinary team
      including gynecologist, surgeon, and urologist performed the surgical cyst
      excision and she has recovered well without any complications. SUMMARY AND
      CONCLUSION: Round ligament serous cystadenomas could grow to any size when there
      is a diagnosis. In addition, even in unusual locations, round ligament serous
      cysts should be kept in the differential diagnosis of abdominal masses.

PMID- 24333107
TI  - Complete androgen insensitivity syndrome with a Sertoli-Leydig cell tumor.
AB  - BACKGROUND: The complete androgen insensitivity (testicular feminization)
      syndrome was described in phenotypic females with 46XY karyotype, presenting with
      primary amenorrhea, adequate breast development, and absent or sparse pubic or
      axillary hair. Gonads consist usually of seminiferous tubules without
      spermatogenesis. CASE: We report the case of a 15-year-old girl with testicular
      feminization since age 4. She was admitted to surgically remove the testes from
      the inguinal canal. Microscopic examination of the left testis revealed a Sertoli
      Leydig cell tumor and the draft of fallopian tube with adjacent seminiferous
      tubules. SUMMARY AND CONCLUSION: These patients have a 5%-10% risk of developing
      germ cell tumors. Sertoli-Leydig cell tumors are uncommon neoplasms, usually
      benign in testicular feminization syndrome.

PMID- 24333108
TI  - The fluctuation of nocturia in men with lower urinary tract symptoms allocated to
      placebo during a 12-month randomized, controlled trial.
AB  - PURPOSE: We determined the fluctuation of nocturia in a 12-month period in men
      with lower urinary tract symptoms. MATERIALS AND METHODS: Men with lower urinary
      tract symptoms were allocated to the placebo arm of the United States Department
      of Veterans Affairs Cooperative Studies Program Benign Prostatic Hyperplasia
      Study. Reported nocturia frequency using the American Urological Association
      Symptom Index was collected at 6 time points (2, 4, 13, 26, 39 and 52 weeks).
      Repeat measurements of nocturia during a 1-year period were analyzed using a
      generalized mixed linear model. RESULTS: Of the 305 men allocated to the placebo
      group 256 participants (84%) gave answers for all 6 time points. In the entire
      sample the mean nocturia count did not significantly vary from baseline (week 2)
      after adjusting for covariates (p = 0.542). However, there was considerable
      fluctuation in nocturia during 1 year. Of the 93 men with 3 or 4 episodes at
      baseline 47% had improvement and 12% had worsening at 1 year. Of the 184 men who
      reported 2 or greater nocturia episodes at baseline 15% reported 0 or 1 at 52
      weeks. Depending on the case definition during followup the probability of
      nocturia progression varied between 8% and 54% while nocturia regression varied
      between 2% and 33%. CONCLUSIONS: Using repeat questionnaire based assessments we
      observed considerable fluctuation in nocturia. However, overall there was no
      significant increase in prevalence in a 1-year period. These findings may be
      reassuring to providers and patients who elect to delay interventions for
      nocturia.

PMID- 24333109
TI  - Incidence and risk factors of parastomal hernia in patients undergoing radical
      cystectomy and ileal conduit diversion.
AB  - PURPOSE: We evaluate the incidence and risk factors of parastomal hernia
      formation in patients undergoing radical cystectomy and ileal conduit urinary
      diversion. MATERIALS AND METHODS: We retrospectively reviewed the Indiana
      University cystectomy database between 2001 and 2011, and identified 516 patients
      who underwent radical cystectomy and ileal conduit diversion. Overall 199
      patients had a clinical followup of at least 12 months and all underwent
      postoperative staging computerized tomography to confirm the presence of
      parastomal hernia. The incidence of parastomal hernia is reported with
      correlations made to demographic, patient level and perioperative risk factors.
      RESULTS: A parastomal hernia developed in 58 patients (29%) at a median followup
      of 27 months (range 12 to 125). Of these patients 26 (45%) underwent surgical
      repair due to abdominal discomfort (58%), acute strangulation or obstruction of
      the small bowel (15%), partial small bowel obstructions (15%) and elective repair
      for other intra-abdominal procedures (12%). Prior exploratory laparotomy
      (adjusted HR 1.98, 95% CI 1.97-3.36, p = 0.011) and severe obesity (adjusted HR
      4.26, 95% CI 1.52-11.93, p = 0.006) were predictive of parastomal herniation. The
      cumulative risk of parastomal hernia formation at 1 and 2 years after cystectomy
      was 12.2% and 22.5%, respectively. CONCLUSIONS: We demonstrated that parastomal
      hernia will develop in nearly a third of patients after radical cystectomy with
      ileal conduit diversion. Prior laparotomy and severe obesity are independent risk
      factors. Preoperative counseling and preventative measures regarding parastomal
      hernia formation should be emphasized, particularly in these at risk patients.

PMID- 24333110
TI  - Late recurrence after radical cystectomy: patterns, risk factors and outcomes.
AB  - PURPOSE: We evaluated the outcome in patients with late recurrence of urothelial
      carcinoma after radical cystectomy. MATERIALS AND METHODS: We identified 2,091
      patients who underwent radical cystectomy at our institution between 1980 and
      2006. Survival was estimated using the Kaplan-Meier method and compared based on
      recurrence timing (less than 5 years vs 5 or greater) and location (urothelial vs
      nonurothelial) using the log rank test. Cox proportional hazard regression models
      were used to evaluate variables associated with late recurrence and death from
      bladder cancer. RESULTS: Median postoperative followup was 16.6 years. Late
      recurrence was identified in 82 patients (3.9%). On multivariate analysis younger
      age (p = 0.0008), nonmuscle invasive disease (p = 0.01) and prostatic urethral
      involvement (p <0.0001) were significantly associated with an increased risk of
      late recurrence. Five-year post-recurrence cancer specific survival was
      significantly worse after recurrence within 5 years from radical cystectomy vs
      after late recurrence (17% vs 37%, p = 0.001). Patients with nonurothelial late
      recurrence had adverse 5-year cancer specific survival compared to those with
      urothelial late recurrence (19% vs 67%, p <0.0001). On multivariate analysis
      younger patient age (HR 1.01, p = 0.003), muscle invasive disease (HR 1.31, p
      <0.0001) and nonurothelial recurrence site (HR 2.76, p <0.0001) but not time to
      recurrence (p = 0.38) were associated with a significantly increased risk of
      death from bladder cancer following recurrence after radical cystectomy.
      CONCLUSIONS: Late recurrence is uncommon after radical cystectomy. Younger
      patient age, nonmuscle invasive disease and prostatic urethral involvement were
      associated with a significantly increased risk of late recurrence. Interestingly,
      time to recurrence was not associated with a subsequent risk of patient death.

PMID- 24333111
TI  - Killed but metabolically active Mycobacterium bovis bacillus Calmette-Guerin
      retains the antitumor ability of live bacillus Calmette-Guerin.
AB  - PURPOSE: Mycobacterium bovis bacillus Calmette-Guerin is the most effective
      treatment for high risk noninvasive bladder cancer. Although bacillus Calmette
      Guerin immunotherapy clearly decreases recurrence and progression rates, side
      effects are common and infection with the bacillus has been described. For these
      reasons it is necessary to find safer alternatives to the live bacillus. We
      explored the possibility of using killed but metabolically active bacillus
      Calmette-Guerin. MATERIALS AND METHODS: T24, J82 and RT4 bladder tumor cell lines
      were cultured with live and irradiation or heat treated bacillus Calmette-Guerin
      Connaught. We measured the inhibition of cell proliferation and the production of
      cytokines in cell culture supernatants. Peripheral mononuclear blood cells were
      also infected and the production of different cytokines in cell culture
      supernatants was analyzed. Peripheral blood mononuclear cell and cell culture
      supernatants activated by mycobacteria were then cultured with T24 cells to
      analyze whether they showed cytotoxic activity. RESULTS: Compared to the other
      bacillus Calmette-Guerin treatments, gamma irradiated bacillus Calmette-Guerin
      showed activity similar to that of the live bacillus for inhibiting tumor growth
      and inducing cytokine production. Irradiated bacillus Calmette-Guerin showed
      metabolic activity and, thus, was considered killed but metabolically active.
      This is the treatment that most accurately preserved the mycobacterial structure.
      Killed but metabolically active bacillus Calmette-Guerin induced cytokine
      production by infected peripheral mononuclear blood cells. Mycobacteria activated
      peripheral blood mononuclear cell and cell supernatants showed cytotoxic activity
      against tumor cells, retaining the antitumor capacity of the live bacillus.
      CONCLUSIONS: Our results suggest that killed but metabolically active bacillus
      Calmette-Guerin could be considered a safer immunotherapy alternative to
      treatment with the live bacillus.

PMID- 24333112
TI  - Potential significance of EMP3 in patients with upper urinary tract urothelial
      carcinoma: crosstalk with ErbB2-PI3K-Akt pathway.
AB  - PURPOSE: Upper urinary tract (pyelocalyceal cavities and ureter) urothelial
      carcinoma is a relatively rare neoplastic disease. Although diagnosis and
      treatment of this tumor variant have improved significantly, accurate risk
      stratification remains a challenge. To identify the putative oncogene involved in
      urothelial carcinoma progression we performed bioinformatics guided experimental
      investigation targeting chromosome 19q13. MATERIALS AND METHODS: We investigated
      the effects of EMP3 on cancer cell growth, migration and adhesion in transfection
      and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was
      examined by reverse transcriptase-polymerase chain reaction and immunoblot. The
      potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was
      analyzed by methylation specific polymerase chain reaction. To validate clinical
      relevance we measured EMP3 expression at the mRNA and protein levels in a cohort
      of 77 patients with upper urinary tract urothelial carcinoma and compared
      prognostic significance in relation to that of ErbB2 expression. RESULTS: We
      noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression
      promoted cancer cell proliferation and migration but suppressed cell adhesion in
      vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in
      vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2
      and EMP3 co-expression was the most important indicator of progression-free and
      metastasis-free survival in patients with upper urinary tract urothelial
      carcinoma (log rank test p = 0.018 and 0.04, respectively). CONCLUSIONS: EMP3 is
      an important prognostic indicator for selecting patients with upper urinary tract
      urothelial carcinoma for more intensive therapy. EMP3 is an innovative co
      targeting candidate for designing ErbB2 based cancer therapy.

PMID- 24333113
TI  - Role of CC chemokine receptor 4 in natural killer cell activation during acute
      cigarette smoke exposure.
AB  - Cigarette smoke (CS)-induced lung injury involves innate immune responses. The
      activation of innate effector cells is thought to require cross talk with
      dendritic cells (DCs) and macrophages, but the mediators of interaction are
      unknown. One candidate, CC chemokine receptor 4 (CCR4), is expressed by innate
      and adaptive effector cells, and its ligands are produced by DCs and macrophages.
      Using flow cytometry and confocal microscopy, we defined innate responses of lung
      myeloid DCs, macrophages, and conventional natural killer (NK) cells in mice
      exposed to CS over 4 days and examined the contribution of CCR4 using CCR4
      knockout (CCR4(-/-)) mice. CS affected populations differently, causing an
      increase in F4/80(+) macrophages, a reduction in parenchymal
      CD11c(+)CD11b(+)CD103(-) DCs, but no effect on mucosal CD11c(+)CD11b(-)CD103(+)
      DCs. CS also induced a population of primed/activated CD69(+) NK cells and
      bronchoepithelial expression of the stress-related NKG2D receptor-activating
      protein, retinoic acid early transcript 1. CS-exposed CCR4(-/-) mice were similar
      to controls regarding effects on DCs and macrophages but displayed substantially
      impaired NK priming/activation and reduced expression of transcripts for
      interferon gamma, CXCL10, and retinoic acid early transcript 1. Quantitative
      confocal microscopy revealed that lungs of CS-exposed CCR4(-/-) mice had
      significantly reduced contacts of NK cells with CD11c(+) cells. These findings
      demonstrate that acute CS exposure elicits NK cell responses and suggest that
      CCR4 promotes NK cell priming/activation by mediating contacts with sentinel
      cells in the lung. 

PMID- 24333114
TI  - Nilotinib 300 mg BID as frontline treatment of CML: prospective analysis of the
      Xpert BCR-ABL monitor system and significance of 3-month molecular response.
AB  - Sixty patients with early chronic phase CML (ECPCML) received Nilotinib on a
      phase II study which included a comparison of the Xpert BCR-ABL MonitorTM PCR
      system with standardized (IS) BCR-ABL1 real-time quantitative PCR (RQ-PCR). 88%
      patients achieved MMR with 45% achieving MR4.5. At 3 months BCR-ABL1/ABL1 IS >1%
      and <10% was associated with a lower likelihood of subsequent MR4.5 compared to
      patients with lower levels (p = 0.018). No significant difference was observed
      between methodologies in identifying MMR. Nilotinib induces high molecular
      response rates in ECPCML and the Xpert BCR-ABL MonitorTM system merits further
      investigation in this setting.

PMID- 24333115
TI  - Transfusion dependence development and disease evolution in patients with MDS and
      del(5q) and without transfusion needs at diagnosis.
AB  - Patients with isolated del(5q) and MDS are considered to have good prognosis as
      compared to other MDS subtypes. Most patients suffered of anemia and 50% of them
      required transfusions at diagnosis. It is known that for patients with MDS and
      del(5q) in transfusion dependence(TD), Lenalidomide is the first choice
      treatment. However, there are no data regarding natural evolution of anemia in
      patients diagnosed in MDS and del(5q) without TD, factors that may impact on the
      development of TD or disease outcome. In the present study we have performed a
      retrospective multicenter analysis on 83 patients with low-int 1 MDS and del(5q)
      without TD. During the study 61 patients became TD at a median of 1.7 years and
      only the Hb level 9 g/dL was associated with poorer TFS (p = 0.007) in the
      multivariate analysis. Among these 61 TD patients, 49 received treatment (19
      Lenalidomide). Median follow up was 48 months, estimated OS at 2 and 5 year was
      92% and 50% respectively. In the multivariate analysis for OS, platelets <100,000
      mm(-3) and Lenalidomide treatment retained the statistical significant impact.
      LFS at 2 and 5 years was 86% and 73% respectively, and median time to sAML was
      8.16 years (CI 95%: 6.05-10.27). In the multivariate analysis only
      thrombocytopenia retained statistical significance. In summary, this
      retrospective study show that level of Hb is an important parameter in order to
      determine the time until TD, it should be also stressed the importance of an
      early treatment in order to prevent TD development and shorter survival.

PMID- 24333116
TI  - Influence of length of time to diagnosis and treatment on the survival of
      children with acute lymphoblastic leukemia: a population-based study.
AB  - The objectives were to describe times to diagnosis and initiation of treatment in
      pediatric ALL in Ontario from 1997 to 2007, and to measure their impact on OS and
      EFS. In 1000 children, the median times to diagnosis and treatment were both 1
      day (IQR = 1-2). Those who began treatment >3 days after diagnosis had inferior
      OS (AHR = 2.49; 95% CI = 1.40-4.43; p = 0.002), and inferior EFS (AHR = 1.73; 95%
      CI = 1.01-2.96; p = 0.047) compared to those who began treatment <= 3 days after
      diagnosis. There was no statistically significant relationship between time to
      diagnosis and survival. Longer time to treatment was associated with worse
      survival in pediatric ALL; reasons for this relationship may be multi-factorial.

PMID- 24333117
TI  - A novel PITX2c loss-of-function mutation associated with familial atrial
      fibrillation.
AB  - Atrial fibrillation (AF) represents the most prevalent form of sustained cardiac
      arrhythmia and contributes substantially to cardiovascular morbidity and
      mortality. Aggregating evidence demonstrates that genetic risk factors play an
      important role in the pathogenesis of AF. However, AF is a genetically
      heterogeneous disease and the genetic defects responsible for AF in an
      overwhelming majority of patients remain unclear. In the present study, the whole
      coding region and splice junction sites of the PITX2c gene, which encodes a
      paired-like homeobox transcription factor essential for normal cardiovascular
      development, were sequenced in 160 unrelated patients with lone AF, and a novel
      heterozygous mutation, c.349C > T equivalent to p.P117S, was identified in a
      patient with positive family history of AF. The missense mutation, which co
      segregated with AF in the family with complete penetrance and was absent in 700
      unrelated ethnically matched healthy individuals, altered the amino acid
      completely conserved evolutionarily across species and was predicted to be
      pathogenic by MutationTaster and PolyPhen-2. Biological assays revealed that the
      mutant PITX2c protein was associated with significantly decreased transcriptional
      activity when compared with its wild-type counterpart. The findings implicate
      PITX2c loss-of-function mutation in familial AF for the first time, providing
      novel insight into the molecular pathology of AF. 

PMID- 24333118
TI  - Exposure to predator odor influences the relative use of multiple memory systems:
      role of basolateral amygdala.
AB  - In a dual-solution plus-maze task in which both hippocampus-dependent place
      learning and dorsolateral striatal-dependent response learning provide an
      adequate solution, the relative use of multiple memory systems can be influenced
      by emotional state. Specifically, pre-training peripheral or intra-basolateral
      (BLA) administration of anxiogenic drugs result in the predominant use of
      response learning. The present experiments were designed to extend these findings
      by examining whether exposure to a putatively ethologically valid stressor would
      also produce a predominant use of response learning. In experiment 1, adult male
      Long-Evans rats were exposed to either a predator odor (trimethylthiazoline
      [TMT], a component of fox feces) or distilled water prior to training in a dual
      solution water plus maze task. On a probe trial 24h following task acquisition,
      rats previously exposed to TMT predominantly displayed response learning relative
      to control animals. In experiment 2, rats trained on a single-solution plus maze
      task that required the use of response learning displayed enhanced acquisition
      following pre-training TMT exposure. In experiment 3, rats exposed to TMT or
      distilled water were trained in the dual-solution task and received post-training
      intra-BLA injections of the sodium channel blocker bupivacaine (1.0% solution,
      0.5 MUl) or saline. Relative to control animals, rats exposed to TMT
      predominantly displayed response learning on the probe trial, and this effect was
      blocked by neural inactivation of the BLA. The findings indicate that (1) the use
      of dorsal striatal-dependent habit memory produced by emotional arousal
      generalizes from anxiogenic drug administration to a putatively ecologically
      valid stressor (i.e. predator odor), and (2) the BLA mediates the modulatory
      effect of exposure to predator odor on the relative use of multiple memory
      systems.

PMID- 24333119
TI  - Update of the Mexican College of Rheumatology guidelines for the pharmacologic
      treatment of rheumatoid arthritis.
AB  - BACKGROUND: The pharmacologic management of rheumatoid arthritis has progressed
      substantially over the past years. It is therefore desirable that existing
      information be periodically updated. There are several published international
      guidelines for the treatment of rheumatoid arthritis that hardly adapt to the
      Mexican health system because of its limited healthcare resources. Hence, it is
      imperative to unify the existing recommendations and to incorporate them to a set
      of clinical, updated recommendations; the Mexican College of Rheumatology
      developed these recommendations in order to offer an integral management approach
      of rheumatoid arthritis according to the resources of the Mexican health system.
      OBJECTIVE: To review, update and improve the available evidence within clinical
      practice guidelines on the pharmacological management of rheumatoid arthritis and
      produce a set of recommendations adapted to the Mexican health system, according
      to evidence available through December 2012. METHODS: The working group was
      composed of 30 trained and experienced rheumatologists with a high quality of
      clinical knowledge and judgment. Recommendations were based on the highest
      quality evidence from the previously established treatment guidelines, meta
      analysis and controlled clinical trials for the adult population with rheumatoid
      arthritis. RESULTS: During the conformation of this document, each working group
      settled the existing evidence from the different topics according to their
      experience. Finally, all the evidence and decisions were unified into a single
      document, treatment algorithm and drug standardization tables. CONCLUSIONS: This
      update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid
      Arthritis provides the highest quality information available at the time the
      working group undertook this review and contextualizes its use for the complex
      Mexican health system.

PMID- 24333120
TI  - Comparable humoral response after two doses of adjuvanted influenza A/H1N1pdm2009
      vaccine or natural infection in allogeneic stem cell transplant recipients.
AB  - BACKGROUND: The present study evaluated immunogenicity and tolerance of two-dose
      influenza A/H1N1pdm09 vaccination in allogeneic hematopoietic stem cell
      transplantation (HSCT) recipients, and compared the vaccine-induced humoral
      response to that triggered by natural infection in another group of HSCT
      patients. METHODS: Adult allogeneic HSCT recipients vaccinated with two doses of
      influenza A/H1N1pdm09 vaccine, separated by 3 weeks, and patients with proven
      influenza A/H1N1pdm09 infection were included. Antibody responses were measured
      by hemagglutination-inhibition assay 1) on days 0, 21, 42 and 6 months after the
      first vaccine injection in vaccinated patients and 2) before pandemic and after
      influenza A/H1N1pdm09 infection, in patients presented natural infection.
      RESULTS: At baseline, 3% of 59 recipients of adjuvanted vaccine and 0% of 20
      infected patients were seroprotected (antibody titer>=1/40). Seroprotection rate
      observed 42 days after vaccination was not different from that observed after
      natural infection (66% and 60% respectively, p=0.78). In vaccinated patients,
      seroprotection rate increased significantly from 54% to 66% between day 21 and 42
      (p=0.015). Moreover, after 6 months, seroprotection rate in 21 vaccinated
      patients was similar to that observed in 10 infected patients evaluated at least
      76 days after infection (D76-217) (60% and 81% respectively, p=0.2). In
      multivariate analysis, no immunosuppressive treatment or chronic graft-versus
      host disease (GVHD) and longer time between transplantation and
      vaccination/infection were associated with a stronger humoral response. The
      adjuvanted vaccine was safe with low rate of GVHD worsening. CONCLUSION: In HSCT
      recipients, two doses of influenza A/H1N1pdm09 adjuvanted vaccine were safe and
      induced a humoral response comparable to that triggered by natural infection in
      these patients.

PMID- 24333121
TI  - Inhibition of glutaminase selectively suppresses the growth of primary acute
      myeloid leukemia cells with IDH mutations.
AB  - The incidence of mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) in de
      novo acute myeloid leukemia (AML) is approximately 20%. These mutations result in
      distinct metabolic characteristics including dependency of cancer cells on
      glutamine as the main source for alpha-ketoglutarate, which is consumed by
      leukemia cells to produce a cancer-derived metabolite, 2-hydroxyglutarate. We
      sought to exploit this glutamine addiction therapeutically in mutant IDH primary
      AML cells from patients by measuring cell growth after exposure to a small
      molecule glutaminase inhibitor, BPTES. We found that BPTES only suppressed the
      growth of AML cells expressing mutant IDH compared with those expressing wild
      type IDH. This study lays the groundwork for strategies to target a specific
      subtype of AML metabolically with IDH mutations with a unique reprogramming of
      intermediary metabolism that culminates in glutamine dependency of cancer cells
      for survival. 

PMID- 24333122
TI  - Modification of recombinant elastase expressed in Pichia pastoris by introduction
      of N-glycosylation sites.
AB  - A novel N-glycosylation site was introduced into recombinant elastase (rPAE) at
      N36, N67, or N264 through the site-directed mutagenesis of I38T, A69T, or N266T,
      respectively. The A69T mutation completely inhibited the expression of rPAE. As
      expected, the I38T and N266T mutant proteins exhibited higher degrees of N
      glycosylation compared with the wild type rPAE. The I38T mutant was more
      efficient in the hydrolysis of casein in aqueous medium and exhibited higher
      specific activity and k(cat) values and a lower K(m) value. In contrast, the
      N266T mutant and the wild type displayed similar values. Importantly, the I38T
      mutant achieved in higher rates and yields of peptide synthesis in 50% (v/v)
      dimethylsulfoxide, whereas the N266T mutant was similar to the wild type rPAE.
      Furthermore, the maximum yield of Z-Ala-Phe-NH2 synthesis catalyzed by the I38T
      mutant protein (87%) was higher than those achieved by the wild type (78%) and
      N266T mutant (78%) proteins. Neither the I38T nor the N266T mutation exerted
      significant effects on the rPAE solvent stability. In aqueous medium, the I38T
      mutation decreased the rPAE thermostability, and the N266T mutation slightly
      improved that. In conclusion, the I38T mutation improved the potential of rPAE in
      industrial applications.

PMID- 24333124
TI  - Maize (Zea mays L.) transformation by Agrobacterium tumefaciens infection of
      pollinated ovules.
AB  - A novel transformation system was established for maize using Agrobacterium
      infection of in vitro cultured ovules. The maize ovules were isolated 24h after
      pollination and infected with Agrobacterium. The embryos were isolated from the
      pollinated ovules 2-3 weeks after Agrobacterium infection, regenerated to
      plantlets and investigated for transgene expression and inheritance. Experimental
      evaluations were focused on the four main aspects. Firstly, through the
      introduction of gus gene for monitoring transformation and development of embryo,
      it was confirmed that transgenic plants can be generated from in vitro cultured
      maize ovules infected with Agrobacterium. Secondly, in order to standardize the
      transformation protocol, several important factors that affected transformation
      efficiency were optimized. They included Agrobacterium delivery approach,
      surfactant, AS concentration, and cocultivation duration. Thirdly, stable
      expression and Mendelian inheritance of the introduced genes were analyzed in
      independent lines over two generations. Fourthly, the pollinated ovule culture
      regeneration potential and transformation efficiency of five maize inbred lines
      were investigated to confirm the genotype independence of this transformation
      system. We conclude that the transformation system established in this study can
      be used to generate high-quality transgenic maize plants rapidly and directly. 

PMID- 24333123
TI  - Virus-free transient protein production in Sf9 cells.
AB  - A method for virus-free transient gene expression from suspension-adapted Sf9
      insect cells was developed with the gene of interest being expressed from a
      plasmid carrying the homologous region 5 enhancer (hr5) and the immediate early 1
      (ie1) promoter from Autographa californica multicapsid nucleopolyhedrovirus
      (AcMNPV). Under the optimal conditions described in the study, cells were
      transfected at a density of 30*106 cells/mL with 0.9 MUg DNA and 1.35 MUg of
      linear 25 kD polyethylenimine (PEI) per million cells. Following transfection,
      the culture was diluted to 4*106 cells/mL for the protein production phase. The
      volumetric yield of tumor necrosis factor receptor (ectodomain) fused to an Fc
      domain (TNFR-Fc) was about 100 MUg/mL for cultures at volumes up to 300 mL. As
      expected, the molecular weight of the dimeric TNFR-Fc produced from Sf9 cells was
      about 6 kDa less than that produced from a recombinant Chinese hamster ovary
      (CHO) cell line due to differences in glycosylation between the two hosts.
      Transient transfection provides an alternative to the baculovirus expression
      vector system (BEVS) for the rapid production of recombinant proteins from Sf9
      cells.

PMID- 24333125
TI  - RNAi-based inhibition of porcine reproductive and respiratory syndrome virus
      replication in transgenic pigs.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is an economically
      devastating viral disease causing heavy losses to the swine industry worldwide.
      Many studies have shown that transient delivery of small interfering RNA (siRNA)
      or adenovirus-mediated RNA interfere (RNAi) could potentially inhibit porcine
      reproductive and respiratory syndrome virus (PRRSV) replication in vivo and in
      vitro. Here, we applied RNAi to produce transgenic (TG) pigs that constitutively
      expressed PRRSV-specific siRNA derived from small hairpin RNA (shRNA). First, we
      evaluated siRNA expression in the founding and F1 generation pigs and confirmed
      stable transmission. Then, we detected the expression of IFN-beta and protein
      kinase R (PKR) and found no difference among TG, non-transgenic (NTG), and wild
      type pigs. Lastly, the F1 generation pigs, including TG and NTG piglets, were
      challenged with 3*104.5 TCID50 of JXA1, a highly pathogenic porcine reproductive
      and respiratory syndrome virus (HP-PRRSV). Our results showed that the in vivo
      siRNA expression substantially reduced the serum HP-PRRSV titers and increased
      survival time by 3 days when TG pigs were compared with the NTG controls. These
      data suggested that RNAi-based genetic modification might be used to breed viral
      resistant livestock with stable siRNA expression with no complications of siRNA
      toxicity.

PMID- 24333127
TI  - Characterization of a novel recombinant beta-glucosidase from Sphingopyxis
      alaskensis that specifically hydrolyzes the outer glucose at the C-3 position in
      protopanaxadiol-type ginsenosides.
AB  - A recombinant beta-glucosidase from Sphingopyxis alaskensis with a specific
      activity of 233.3Umg(-1) was purified by His-trap chromatography. The native
      enzyme was a 206kDa tetramer. The maximum enzyme activity was observed at pH 5.5
      and 50 degrees C. However, above 40 degrees C, the enzyme stability significantly
      decreased. The enzyme hydrolyzed only the outer glucose at the C-3 position in
      protopanaxadiol-type ginsenosides without further hydrolysis. Because of the
      narrow substrate specificity, the enzyme completely converted ginsenosides Rb1,
      Rb2, Rc, and Rd as substrates to gypenoside XVII, compound O, compound Mc1, and
      F2, respectively, and it converted ginsenoside Rg3 to Rh2 with a molar conversion
      yield of 89%. These results suggest that the recombinant beta-glucosidase from S.
      alaskensis is a potential producer of the rare ginsenosides gypenoside XVII,
      compound O, compound Mc1, F2, and Rh2. Among ginsenoside substrates, Rb1 was used
      for the high-level production of the rare ginsenoside gypenoside XVII. The
      optimum reaction conditions were pH 5.5, 40 degrees C, 0.5mgml(-1) (116.7Uml(-1))
      enzyme, and 8.0gl(-1) ginsenoside Rb1. Under these conditions, 6.8gl(-1)
      gypenoside XVII was produced by the enzyme after 1h with a molar conversion yield
      of 100% and a productivity of 6.8gl(-1)h(-1). 

PMID- 24333126
TI  - The effect of O-methylated flavonoids and other co-metabolites on the
      crystallization and purification of artemisinin.
AB  - Methoxylated flavonoids casticin, artemetin and retusin were identified as
      putative causative factors for low crystallization yields of artemisinin from
      extracts. Comparative profiling of biomass grown in different countries found
      elevated levels (~60% higher) of artemetin in the East African biomass, which
      also demonstrates poor crystallization yields. The single compound and the
      combined doping experiments at 0, 25 and 50 MUg mL-1 doping levels showed that
      artemetin (50 MUg mL-1) caused a reduction in the amount of artemisinin
      crystallized by ca. 60%. A combination of the three flavonoids at 50 MUg mL-1
      almost completely inhibited crystallization, reducing the yield by 98%. Treatment
      of extracts by adsorbents efficiently resolves the problem of low crystallization
      yield.

PMID- 24333128
TI  - Production of rotavirus core-like particles in Sf9 cells using recombinase
      mediated cassette exchange.
AB  - A flexible Sf9 insect cell line was recently developed leveraging the recombinase
      mediated cassette exchange (RMCE) technology, which competes with the popular
      baculovirus expression vector system (BEVS) in terms of speed to produce new
      proteins. Herein, the ability of this cell platform to produce complex proteins,
      such as rotavirus core-like particles, was evaluated. A gene construct coding for
      a VP2-GFP fusion protein was targeted to a pre-characterized high recombination
      efficiency locus flanked by flipase (Flp) recognition target sites and, after
      three weeks in selection, an isogenic cell population was obtained. Despite the
      lower cell specific productivities with respect to those obtained by baculovirus
      infection, the titers of VP2-GFP reached in shake flask batch cultures were
      comparable as a result of higher cell densities. To further improve the VP2-GFP
      levels from stable expression, analysis of exhausted medium was undertaken to
      design feeding strategies enabling higher cell densities as well as increased
      culture duration. The implementation of the best strategy allowed reaching 20
      million cells per ml in bioreactor cultures; the integrity of the rotavirus core
      like particles could be confirmed by electron microscopy. Overall, we show that
      this Sf9-Flp cell platform represents a valuable alternative to the BEVS for
      producing complex recombinant proteins, such as rotavirus core-like particles. 

PMID- 24333129
TI  - The bacterial Entner-Doudoroff pathway does not replace glycolysis in
      Saccharomyces cerevisiae due to the lack of activity of iron-sulfur cluster
      enzyme 6-phosphogluconate dehydratase.
AB  - Replacement of the glycolytic pathway of Saccharomyces cerevisiae by a bacterial
      Entner-Doudoroff pathway (EDP) would result in lower ATP production and therefore
      a lower biomass yield is expected that would further allow higher products yields
      in the fermentation of sugars. To establish catabolism of glucose via the EDP in
      S. cerevisiae requires expression of only two additional enzyme activities, 6
      phosphogluconate dehydratase (PGDH) and KDPG aldolase. In this work, KDPG
      aldolase from Escherichia coli could be successfully expressed in the yeast
      cytosol with very high enzyme activity. Nevertheless, simultaneous expression of
      KDPG aldolase and a codon optimized PGDH gene of E. coli could not replace
      glycolysis or the pentose phosphate pathway in growth experiments. It could be
      shown that this was due to the very low enzyme activity of PGDH. This bacterial
      enzyme is a [4Fe-4S] iron-sulfur cluster protein. Several attempts to improve the
      availability of iron-sulfur clusters or iron in the yeast cells, to attract the
      iron-sulfur cluster assembly machinery to Leu1-PGDH fusion proteins or to
      localize the PGDH in the mitochondria did not result in improved enzyme
      activities. From our results we conclude that establishing functional expression
      of iron-sulfur cluster enzymes will be a major task for the integration of the
      EDP and other biochemical pathways in yeast. 

PMID- 24333130
TI  - Complete genome sequence of Bacillus thuringiensis YBT-1518, a typical strain
      with high toxicity to nematodes.
AB  - Bacillus thuringiensis is a ubiquitous spore-forming bacterium and has been
      widely used as a biopesticide for controlling agricultural insects by the
      production of insecticidal crystal proteins (ICPs). B. thuringiensis YBT-1518
      displays effective toxicity to nematodes. This strain harbors three nematicidal
      crystal protein genes, including cry55Aa1, cry6Aa2 and cry5Ba2, and also contains
      multiple potential virulence factors. Here, we report the complete genome
      sequence of B. thuringiensis YBT-1518, which consists of one circular chromosome
      and six circular plasmids. 

PMID- 24333131
TI  - A myostatin and activin decoy receptor enhances bone formation in mice.
AB  - Myostatin is a member of the bone morphogenetic protein/transforming growth
      factor-beta (BMP/TGFbeta) super-family of secreted differentiation factors.
      Myostatin is a negative regulator of muscle mass as shown by increased muscle
      mass in myostatin deficient mice. Interestingly, these mice also exhibit
      increased bone mass suggesting that myostatin may also play a role in regulating
      bone mass. To investigate the role of myostatin in bone, young adult mice were
      administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble
      myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors
      increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction
      (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal
      femur and lumbar vertebrae, respectively. Histological evaluation demonstrated
      that increased BV/TV in both locations was attributed to increased trabecular
      thickness, trabecular number and bone formation rate. Increased BV/TV resulted in
      enhanced vertebral maximum compressive force compared to untreated animals. The
      fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this
      soluble decoy receptor may be binding a ligand other than myostatin, that plays a
      role in regulating bone mass. This was confirmed by the significant increase in
      BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known
      ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone
      mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar
      increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This
      result suggests that BMP3 neutralization is not the mechanism responsible for
      increased bone mass. The results of this study demonstrate that ActRIIB-Fc
      increases both muscle and bone mass in mice. Therefore, a therapeutic that has
      this dual activity represents a potential approach for the treatment of frailty. 

PMID- 24333132
TI  - EGFR inhibition by pentacyclic triterpenes exhibit cell cycle and growth arrest
      in breast cancer cells.
AB  - AIMS: Pentacyclic triterpenes are a group of molecules with promising anticancer
      potential, although their precise molecular target remains elusive. The current
      work aims to investigate the antiproliferative and associated mechanisms of
      triterpenes in breast cancer cells in vitro. MAIN METHODS: Effect of triterpenes
      on cell cycle distribution, ROS and key regulatory proteins were analyzed in
      three breast cancer cells in vitro. Growth inhibition, new DNA synthesis, colony
      formation assays and Western blot analysis were performed to assess the EGFR
      inhibitory effect of triterpenes. Molecular docking was performed to study the
      interaction between EGFR and triterpenes. KEY FINDINGS: We have demonstrated the
      ability of dimethyl melaleucate (DMM), a pentacyclic triterpene to exhibit cell
      cycle arrest at G0/G1 phase by down-regulation of cyclin D1 through PI3K/AKT
      inhibition. Further, to identify the upstream target of DMM, potential EGFR
      inhibitory activity of DMM and three structurally related pentacyclic
      triterpenes, ursolic acid, 18alpha-glycyrrhetinic acid and carbenoxolone was
      investigated. Interestingly, pentacyclic triterpenes limit EGF mediated breast
      cancer proliferation through sustained inhibition of EGFR and its downstream
      effectors STAT3 and cyclin D1 in breast cancer lines. We also show pentacyclic
      triterpenes to bind at the ATP binding pocket of tyrosine kinase domain of EGFR
      leading to the hypothesis that pentacyclic triterpenes could be a novel class of
      EGFR inhibitors. In conclusion, pentacyclic triterpenes inhibit EGFR activation
      through binding with tyrosine kinase domain thereby suppressing breast cancer
      proliferation. SIGNIFICANCE: Pentacyclic triterpenes may serve as a potential
      platform for development of novel drugs against breast cancer.

PMID- 24333133
TI  - Continuous oral administration of atorvastatin ameliorates brain damage after
      transient focal ischemia in rats.
AB  - AIMS: Pre-treatment with statins is known to ameliorate ischemic brain damage
      after experimental stroke, and is independent of cholesterol levels. We undertook
      pre- vs post-ischemic treatment with atorvastatin after focal cerebral ischemia
      in rats. MAIN METHODS: Male Sprague-Dawley rats underwent transient 90-min middle
      cerebral artery occlusion (MCAO). Atorvastatin (20mg/kg/day) or vehicle was
      administered orally. Rats were divided into vehicle-treated, atorvastatin pre
      treatment, atorvastatin post-treatment, and atorvastatin continuous-treatment
      groups. In the pre-treatment, rats were given atorvastatin or vehicle for 7 days
      before MCAO. In the post-treatment, rats received atorvastatin or vehicle for 7
      days after MCAO. Measurement of infarct volume, as well as neurological and
      immunohistochemical assessments, were done 24h and 7 days after reperfusion. KEY
      FINDINGS: Each atorvastatin-treated group demonstrated significant reductions in
      infarct and edema volumes compared with the vehicle-treated group 24h after
      reperfusion. Seven days after reperfusion, infarct volumes in the post-treatment
      group and continuous-treatment group (but not the pre-treatment group) were
      significantly smaller than in the vehicle-treated group. Only the continuous
      treatment group had significantly improved neurological scores 7 days after
      reperfusion compared with the vehicle group. Post-treatment and continuous
      treatment groups had significantly decreased lipid peroxidation, oxidative DNA
      damage, microglial activation, expression of tumor necrosis factor-alpha, and
      neuronal damage in the cortical ischemic boundary area after 7 days of
      reperfusion. SIGNIFICANCE: These results suggest that continuous oral
      administration (avoiding withdrawal) with statins after stroke may reduce the
      extent of post-ischemic brain damage and improve neurological outcome by
      inhibiting oxidative stress and inflammatory responses.

PMID- 24333134
TI  - Retroperitoneal Castlemans disease associated with paraneoplastic pemphigus.
AB  - Paraneoplastic pemphigus is a rare dermatologic condition that can occur as a
      paraneoplastic manifestation of lymphoproliferative disorders, visceral
      malignancies, Castleman disease and thymomas. In a pediatric age group
      paraneoplastic pemphigus has a striking association with Castleman disease and
      has a particularly poor prognosis in this age group. We describe a case of
      paraneoplastic pemphigus associated with retroperitoneal hyaline vascular variant
      of Castleman disease with a fatal outcome despite aggressive management. 

PMID- 24333135
TI  - Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced
      hepatocellular carcinoma: an open-label Phase II feasibility study.
AB  - PURPOSE: Sorafenib is considered a standard of care in advanced hepatocellular
      carcinoma (HCC). Its combination with gemcitabine, a pyrimidine analogue with
      limited friendly hepatic profile may prove beneficial in advanced HCC. The
      primary objective was to evaluate the efficacy and safety of a sorafenib and
      gemcitabine combination in patients with advanced HCC. METHODS: This was a non
      randomized, open-label, single-arm, multi-centric Phase II study conducted in
      Pakistan where 30 treatment-naive patients aged between 26 and 73 years with
      Child-Pugh score A or B were treated with sorafenib (400 mg oral) twice daily for
      16 weeks along with gemcitabine (1000 mg/m(2) intravenous) administered on day 1
      and day 8 of a four-week cycle for 16 weeks. RESULTS: Of the 18 patients (60%)
      who completed all four cycles of treatment, eight patients had stable disease,
      two had partial response, and eight had progressive disease. There was no
      complete response. The most common (>=10% patients) treatment-emergent adverse
      events were gemcitabine-related thrombocytopenia (40%) followed by sorafenib
      related hand-foot skin reaction and anorexia (33% each). CONCLUSION: The efficacy
      of sorafenib gemcitabine combination therapy is similar to the sorafenib alone
      treatment. However, frequent dose adjustments due to gemcitabine-related
      toxicities, delays, and corrective treatments make this combination therapy
      unsafe in the treatment of advanced HCC.

PMID- 24333136
TI  - Severe combined immunodeficiency caused by a new homozygous RAG1 mutation with
      progressive encephalopathy.
AB  - We describe an unusual case of severe combined immunodeficiency (SCID) with
      neutropenia and central nervous system (CNS) manifestations in which a novel RAG1
      mutation was identified. A 15-month-old boy presented with failure to thrive,
      neutropenia and recurrent infections. He was diagnosed with T-B-NK+ SCID. He
      subsequently developed right partial seizures with ipsilateral hemiparesis and
      became comatose. Magnetic resonance imaging (MRI) of the brain revealed an
      inflammatory lesion in the left thalamus which later progressed to diffuse
      meningo-encephalitis on serial imaging. No CNS infection was documented. Genetic
      work-up in the child revealed a novel homozygous deleterious mutation in the RAG1
      gene (c:2881T>C; p:I794T), for which both parents were heterozygous. He underwent
      a haploidentical bone marrow transplant without conditioning and died on day +35
      with no improvement in his neurological status. The features of neutropenia and
      progressive encephalopathy could be linked to the novel genetic defect but more
      data is required to establish this conclusively. 

PMID- 24333137
TI  - Glucocorticoid receptors on and in a unicellular organism, Cryptobia salmositica.
AB  - This is the first report to our knowledge that demonstrates a functional steroid
      hormone receptor in a protozoon. The study used Cryptobia salmositica, a
      pathogenic haemoflagellate found in salmonid fishes. It has been previously shown
      that cortisol and dexamethasone (a synthetic glucocorticoid) enhanced the
      multiplication of C. salmositica under in vitro conditions indicating the
      presence of glucocorticoid receptors on/in the parasite. Also, the glucocorticoid
      receptor antagonist, mifepristone (RU486), inhibited the stimulatory effect of
      the two glucocorticoids on parasite multiplication. In the present study, we used
      an antibody (produced in a rabbit against glucocorticoid receptor protein)
      agglutination test and confocal microscopy with immunohistofluorescence staining
      to demonstrate cortisol-glucocorticoid receptor-like protein receptors on the
      plasma membrane and in the cytoplasm of the parasite. In two in vitro studies,
      the addition of 50ngml(-1) of RU486 was more effective in inhibiting parasite
      replication in cultures with 7,000parasitesml(-1) than in cultures with
      14,000parasitesml(-1). Also, 100ngml(-1) of RU486/ml was more effective than
      50ngml(-1) in inhibiting parasite multiplication in the 14,000 parasitesml(-1)
      cultures. These in vitro studies indicate that the number of binding sites on/in
      the parasite is finite. The findings may be important in future studies
      especially on steroid receptor signalling pathways and dissection of ligand
      receptor interactions, and for evaluating the adaptations that develop in
      pathogens as part of the host-parasite interaction. 

PMID- 24333138
TI  - [Response to "Spectrum of gluten-sensitive entheropathy in patients with
      dismotility-like dyspepsia"].

PMID- 24333139
TI  - [Acute pericarditis associated with oral or topical mesalazine therapy in
      patients with ulcerative colitis].

PMID- 24333140
TI  - The distinctive regulatory roles of PrtT in the cell metabolism of Penicillium
      oxalicum.
AB  - PrtT is a fungal-specific transcription activator of extracellular proteases in
      Aspergilli. In this study, the roles of the PrtT homolog from Penicillum oxalicum
      was investigated by transcription profiling in combination with electrophoretic
      mobility shift assay (EMSA). The prtT deletion dramatically reduced extracellular
      protease activities and caused intracellular nutrient limitation when cultured on
      casein as the sole carbon source. PrtT was found to directly regulate the
      expression of an intracellular peptidase encoding gene (tripeptidyl-peptidase)
      and the gene encoding the extracellular dipeptidyl-aminopeptidase V, in addition
      to the expected extracellular peptidase genes (carboxypeptidase and
      aspergillopepsin). Five amylase genes (alpha-amylase, glucoamylase, alpha
      glucosidase) and three major facilitator superfamily transporter genes related to
      maltose, monosaccharide and peptide transporting were also confirmed as putative
      targets of PrtT by EMSA. In contrast, the transcription levels of other genes
      encoding polysaccharide degrading enzymes (e.g. cellulases) and most iron or
      multidrug transporter encoding genes were up- or down-regulated in the DeltaprtT
      mutant due to nutrient limitation resulting from the reduced usage of the sole
      carbon source, casein. These results deepen the understanding of the interaction
      of regulation systems for nitrogen and carbon catabolism, which benefit strain
      improvement of P. oxalicum for industrial enzyme production. 

PMID- 24333141
TI  - Serum anion gap is predictive of mortality in an elderly population.
AB  - An elevated serum anion gap is known to be associated with hypertension, low
      cardiorespiratory fitness, and decreased renal function. We evaluated whether
      serum AG might be predictive of elderly mortality in a community-based cohort in
      Korea. We analyzed the available data from 862 elderly people in the Korean
      Longitudinal Study on Health and Aging. Over a 5-year observational period,
      151/862 (17.5%) participants died, and a high albumin-adjusted anion gap (SAAG)
      was associated with an increased risk of all-cause mortality in unadjusted
      analyses (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.41-2.71) and
      fully adjusted analyses (HR, 1.77; 95% CI, 1.24-2.52), compared with a low SAAG
      group. The population attributable fraction of death due to high SAAG was 38.2%
      (95% CI 20.7-58.2%). In particular, the participants with high SAAG had higher
      cardiovascular and infection-related mortality rates than those with low SAAG
      (HR, 2.11; 95% CI, 1.06-4.19, and HR, 9.69; 95% CI, 1.12-83.4, respectively).
      High SAAG may be an independent predictor of mortality and is associated with
      higher cardiovascular and infection related mortality in the elderly. 

PMID- 24333142
TI  - Mammalian target of rapamycin inhibitors permit regulatory T cell reconstitution
      and inhibit experimental chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) remains a major late complication of
      allogeneic bone marrow transplantation (BMT). In a previous study, impaired
      thymic negative selection of the recipients permitted the emergence of pathogenic
      T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into
      C3H model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD
      when administered into the secondary recipients. In this study, we evaluated the
      kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H
      model. After myeloablative conditioning, host Tregs disappeared rapidly, followed
      by expansion of Tregs derived from the donor splenic T cell inoculum. However,
      the donor splenic T cell-derived Treg pool contracted gradually and was almost
      completely replaced by newly generated donor bone marrow (BM)-derived Tregs in
      the late post-transplantation period. Next, we compared the effects of
      cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg
      reconstitution. Administration of CSA significantly impaired Treg reconstitution
      in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not
      impaired in mTOR inhibitor-treated mice. Histopathological examination indicated
      that mice treated with CSA, but not mTOR inhibitors, showed pathogenic features
      of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR
      inhibitors, developed severe chronic GVHD followed by adoptive transfer of the
      pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings
      indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs
      and increases the liability to chronic GVHD. The choice of immunosuppression,
      such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have
      important implications for the control of chronic GVHD after BMT. 

PMID- 24333143
TI  - Bioluminescent tracking of colonization and clearance dynamics of plasmid
      deficient Yersinia pestis strains in a mouse model of septicemic plague.
AB  - Yersinia pestis 201 contains 4 plasmids pPCP1, pMT1, pCD1 and pCRY, but little is
      known about the effects of these plasmids on the dissemination of Y. pestis. We
      developed a plasmid-based luxCDABE bioreporter in Y. pestis 201, Y. pestis 201
      pCD1(+), Y. pestis 201-pMT1(+), Y. pestis 201-pPCP1(+), Y. pestis 201-pCRY(+), Y.
      pestis 201-p(-) and Yersinia pseudotuberculosis Pa36060 strains, and investigated
      their dissemination by bioluminescence imaging during primary septicemic plague
      in a mouse model. These strains mainly colonized the livers and spleens shortly
      after intravenous inoculation. Y. pestis 201-pMT1(+) appeared to have a stronger
      ability to survive in the livers, spleens and blood, and to be more virulent than
      other plasmid-deficient strains. Y. pestis 201-pPCP1(+) appeared to have a
      stronger ability to colonize lungs than other plasmid-deficient strains. Pa36060
      has the strongest ability to colonize intestines and lungs. Y. pestis 201 has the
      strongest ability to survive in blood, and the strongest virulence. These results
      indicated that the plasmid pMT1 was an important determinant in the colonization
      of livers, spleens and blood, whereas the plasmid pPCP1 appeared to correlate
      with the colonization in lungs. The resistance to killing in mouse blood seemed
      to be the critical factor causing animal death.

PMID- 24333144
TI  - Modeling PHA-producing microbial enrichment cultures--towards a generalized model
      with predictive power.
AB  - Polyhydroxyalkanoate (PHA) production from waste streams using microbial
      enrichment cultures is a promising option for cost price reduction of this
      biopolymer. For proper understanding and successful optimization of the process,
      a consistent mechanistic model for PHA conversion by microbial enrichment
      cultures is needed. However, there is still a lack of mechanistic expressions
      describing the dynamics of the feast-famine process. The scope of this article is
      to provide an overview of the current models, investigate points of improvement,
      and contribute concepts for creation of a generalized model with more predictive
      value for the feast-famine process. Based on experimental data available in
      literature we have proposed model improvements for (i) modeling mixed substrates
      uptake, (ii) growth in the feast phase, (iii) switching between feast and famine
      phase, (iv) PHA degradation and (v) modeling the accumulation phase. Finally, we
      provide an example of a simple uniform model. Herewith we aim to give an impulse
      to the establishment of a generalized model. 

PMID- 24333145
TI  - Improved propionic acid production from glycerol with metabolically engineered
      Propionibacterium jensenii by integrating fed-batch culture with a pH-shift
      control strategy.
AB  - Propionic acid (PA) production with metabolically engineered Propionibacterium
      jensenii (pZGX04-gldA) was improved by integrating fed-batch culture with a two
      stage pH control strategy in a 3-L fermenter. The following two-stage pH control
      strategy was used: the pH was controlled at 5.9 for 0-36 h and shifted to 6.5
      after 36 h. The PA titer was increased to 21.43 g/L. On the basis of pH control,
      the influence of fed-batch culture on PA production was further investigated and
      the maximum PA production (34.62 g/L) was obtained when glycerol was fed at a
      constant rate of 3.33 mL/h from 60 to 132 h with an initial glycerol
      concentration of 25 g/L. Crude glycerol was then used to produce PA using the
      optimized strategies, and maximal PA production reached 37.26 g/L. The strategies
      may be useful for the production of PA by other propionibacteria species.

PMID- 24333146
TI  - Effect of barium ferrite particle size on detachment efficiency in
      magnetophoretic harvesting of oleaginous Chlorella sp.
AB  - Microalgal biofuel is garnering many positive and promising reviews as a fuel for
      the next generation while research effort continues to improve the efficiency of
      its harvesting for commercial success. In this report, magnetophoretic harvesting
      of microalgae is conducted through a three-step process, which includes
      functionalization of magnetic particles by (3-aminopropyl)triethoxysilane
      (APTES), magnetic separation, and detachment of magnetic particles by increasing
      pH to higher than the isoelectric point. Detachment process is specifically
      focused and found that the use of larger magnetic particles is more efficient for
      detachment of magnetic particles from algae-particle conglomerates. The detaching
      efficiency improves from 12.5% to 85% when the particle size is increased from
      108 nm to 1.17 MUm. Smaller magnetic particles provide larger contact area to
      microalgae and form strong electrostatic binding to negatively-charged microalgae
      when pH is lower than the isoelectric point.

PMID- 24333147
TI  - Buspirone anti-dyskinetic effect is correlated with temporal normalization of
      dysregulated striatal DRD1 signalling in L-DOPA-treated rats.
AB  - Dopamine replacement with l-DOPA is the most effective therapy in Parkinson's
      disease. However, with chronic treatment, half of the patients develop an
      abnormal motor response including dyskinesias. The specific molecular mechanisms
      underlying dyskinesias are not fully understood. In this study, we used a well
      characterized animal model to first establish the molecular differences between
      rats that did and did not develop dyskinesias. We then investigated the molecular
      substrates implicated in the anti-dyskinetic effect of buspirone, a 5HT1A partial
      agonist. Striatal protein expression profile of dyskinetic animals revealed
      increased levels of the dopamine receptor (DR)D3, DeltaFosB and phospho (p)CREB,
      as well as an over-activation of the DRD1 signalling pathway, reflected by
      elevated ratios of phosphorylated DARPP32 and ERK2. Buspirone reduced the
      abnormal involuntary motor response in dyskinetic rats in a dose-dependent
      fashion. Buspirone (4 mg/kg) dramatically reduced the presence and severity of
      dyskinesias (by 83%) and normalized DARPP32 and ERK2 phosphorylation ratios,
      while the increases in DRD3, DeltaFosB and pCREB observed in dyskinetic rats were
      not modified. Pharmacological experiments combining buspirone with 5HT1A and DRD3
      antagonists confirmed that normalization of both pDARPP32 and pERK2 is required,
      but not sufficient, for blocking dyskinesias. The correlation between pDARPP32
      ratio and dyskinesias was significant but not strong, pointing to the involvement
      of convergent factors and signalling pathways. Our results suggest that in
      dyskinetic rats DRD3 striatal over-expression could be instrumental in the
      activation of DRD1-downstream signalling and demonstrate that the anti-dyskinetic
      effect of buspirone in this model is correlated with DRD1 pathway normalization. 

PMID- 24333148
TI  - The involvement of the GPR39-Zn(2+)-sensing receptor in the pathophysiology of
      depression. Studies in rodent models and suicide victims.
AB  - Zinc is one of the most important trace elements in our body. Patients suffering
      from depression show lower serum zinc levels compared to healthy controls. Zincs
      antagonism to the glutamatergic system seems to be responsible for mood recovery.
      Recent years have shown that zinc may regulate neurotransmission via the
      metabotropic GPR39 receptor. Activation of the GPR39-Zn(2+)-sensing receptor
      (GPR39) triggers diverse neuronal pathways leading to a cAMP-responsive element
      binding the protein (CREB) expression, which then induces synthesis of the brain
      derived neurotrophic factor and, in turn, activation of the Tropomyosin receptor
      kinase B (TrkB) receptor. In the present study, we investigated the alteration of
      the GPR39 in different models of depression, such as zinc deficiency and
      olfactory bulbectomy and in suicide victims. Additionaly, we focused on CREB
      BDNF/TrkB under zinc deficient conditions in mice. To demonstrate depressive-like
      behaviour, a standard and modified forced swim test (FST) was performed. To
      evaluate expression of GPR39, CREB, BDNF and TrkB, Western Blot analysis was
      used. Zinc deficient mice and rats showed decreased GPR39 expression in the
      hippocampus and frontal cortex. A decreased level of hippocampal and cortical
      GPR39 was also observed in suicide victims. In contrast, increased GPR39 in the
      hippocampus of olfactory bulbectomized rats was observed. Additionally, we found
      a decreased expression of CREB, BDNF and TrkB only in the hippocampus of zinc
      deficient mice. Our present study demonstrates the associacion of the GPR39
      Zn(2+)-sensing receptor in the pathomechanism of depression. Down-regulation of
      CREB, BDNF, TrkB and GPR39 receptor found under zinc-deficient conditions in the
      hippocampus, may play an important role in the pathophysiology of mood disorders,
      since most of patients suffering from depression show lower serum zinc. 

PMID- 24333149
TI  - Analysis of odorant-binding protein gene family members in the polyembryonic
      wasp, Copidosoma floridanum: evidence for caste bias and host interaction.
AB  - The polyembryonic wasp Copidosoma floridanum produces two larval castes, soldiers
      and reproductives, during development within its caterpillar host. Primary
      structures were determined for 6 odorant-binding protein (OBP) gene family
      members in Copidosoma and then analyzed alongside two formerly sequenced OBP
      genes from this wasp. The genes were examined for caste-bias in expression
      patterns using reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ expression studies. Six of the 8 genes show a clear bias in gene expression
      towards one or the other larval caste. Of the 3 distinct in situ probe
      hybridization patterns observed in this study, none lie in tissues with clear
      chemosensory functions. Two of the patterns suggest the majority of the
      Copidosoma OBP gene family members discovered thus far come into contact with
      host hemolymph. Most of these OBPs are expressed exclusively in the serosal
      membrane encompassing each of the reproductive larvae. The absence of expression
      in the membrane surrounding soldier larvae strongly suggests these OBPs are
      performing caste-specific functions in the host. 

PMID- 24333150
TI  - Latitudinal clines in heat tolerance, protein synthesis rate and transcript level
      of a candidate gene in Drosophila melanogaster.
AB  - The occurrence of climatic adaptation in Drosophila melanogaster is highlighted
      by the presence of latitudinal clines in several quantitative traits,
      particularly clines in adult heat knockdown tolerance that is higher in tropical
      populations. However the presence of latitudinal patterns in physiological
      characteristics that may underlie these traits have rarely been assessed. Protein
      synthesis has been implicated as an important physiological process that
      influences thermal tolerance, and this has not been examined in a clinal context.
      Here, we characterise latitudinal variation in D. melanogaster from eastern
      Australia in both adult heat knockdown tolerance and rates of protein synthesis
      following rearing at both 25  degrees C, approximating summer conditions, and 18 
      degrees C approximating winter development. We also examined clinal variation in
      the predominant nuclear transcript of the heat-inducible RNA gene hsr-omega,
      which has been implicated in regulating protein synthesis. We find significant
      clines in heat-hardened tolerance when cultured at both 18 and 25  degrees C -
      tolerance increased towards the low latitude tropics. Rates of protein synthesis
      measured in ovarian tissue also associated negatively with latitude, however the
      presence of the clines depended on rearing temperature and heat stress
      conditions. Finally, omega-n levels measured without heat stress showed a
      positive linear cline. When measured after a mild heat stress higher levels of
      omega-n were detected and the clinal pattern became parabolic - mid-latitude
      populations had lower levels of the transcript. While congruent latitudinal
      trends were detected for these three traits, only a low level of positive
      association was detected between protein synthesis and thermal tolerance
      providing little evidence that these traits are related at the level of cellular
      physiology. However the new clinal patterns of protein synthesis and hsr-omega
      variation suggest that these variables exert important influences on traits
      involved with latitudinal climatic adaptation.

PMID- 24333151
TI  - Characterization of male-derived factors inhibiting female sexual receptivity in
      Lygus hesperus.
AB  - Newly mated females of the plant bug, Lygus hesperus Knight, enter a refractory
      period during which their sexual receptivity to courting males is greatly reduced
      for several days. This behavioral change appears to be induced by male-derived
      factors delivered in the spermatophore during copulation. To better understand
      the source of the factor(s) responsible for the inhibition, the homogenates of
      spermatophores, or of the individual organs that provide the constituents of the
      spermatophore, were injected directly into the abdomen of virgin females. The
      contents of the lateral and medial accessory glands both appear to produce
      inhibitory effects, but those of the seminal vesicle had no effect. Treatment of
      the homogenate also indicated that the active factor(s) is heat labile and water
      soluble. Several unique proteins were found in the water soluble fraction of the
      spermatophore, one of which is similar in size to the Drosophila melanogaster sex
      peptide, a male derived compound known to inhibit receptivity in female flies. In
      addition, spermatophores contained a substantial quantity of juvenile hormone, a
      key endocrine regulator of reproductive behavior and physiology in most insects.
      The results support the hypothesized role of males in manipulating the post
      mating behavior of females, and suggest this is achieved through multiple
      components that act in concert to induce both short- and long-term effects. 

PMID- 24333152
TI  - A ferromagnetic model for the action of electric and magnetic fields in
      cryopreservation.
AB  - Recent discussions in the literature have questioned the ability of
      electromagnetic exposure to inhibit ice crystal formation in supercooled water.
      Here we note that strong electric fields are able to disrupt the surface boundary
      layer of inert air on the surface of materials, promoting higher rates of heat
      transport. We also note that most biological tissues contain ferromagnetic
      materials, both biologically precipitated magnetite (Fe3O4) as well as
      environmental contaminants that get accidentally incorporated into living
      systems. Although present at trace levels, the number density of these
      particulates is high, and they have extraordinarily strong interactions with
      weak, low-frequency magnetic fields of the sort involved in claims of
      electromagnetic cryopreservation. Magnetically-induced mechanical oscillation of
      these particles provides a plausible mechanism for the disruption of ice-crystal
      nucleation in supercooled water.

PMID- 24333153
TI  - Mutagenesis of hepatitis E virus helicase motifs: effects on enzyme activity.
AB  - Hepatitis E virus (HEV), the causative agent of hepatitis E, is a non-enveloped
      RNA virus. The open reading frame 1 encoded non-structural polyprotein has
      putative domains for methyltransferase, cysteine protease, helicase and RNA
      dependent RNA polymerase, however processing of this polyprotein is still
      uncertain. HEV helicase belongs to superfamily 1 and has all seven conserved
      motifs typical of the family. NTPase and RNA duplex unwinding activities of HEV
      helicase domain were recently demonstrated by us. A non-radioactive RNA unwinding
      assay was developed using biotin and digoxigenin labeled duplex RNA substrate
      with 5' overhangs for measuring strand displacement activity of the helicase. A
      series of deletion mutants were constructed to investigate role of individual
      motifs in the enzymatic activities. Deletion mutants for motif M I and M IV
      showed increase in ATPase activity. Deletion mutant M VI retained ATPase activity
      comparable to wild type protein. Mutant M II showed reduced ATPase activity
      (P=0.003) with no significant decrease in unwinding activity while mutants M Ia
      and M III showed major reduction of both ATPase and unwinding activities
      indicating crucial role of these motifs in the helicase function. Overall
      analysis of deletion mutants showed that Motif I, IV, V and VI have alternative
      motifs to carry out enzymatic functions of the protein while motifs Ia and III
      are critical as well as unique motifs in the protein. Knowing the important role
      of helicase protein during positive sense RNA virus replication, these unique
      motifs could be good antiviral targets. 

PMID- 24333154
TI  - Model for tumour growth with treatment by continuous and pulsed chemotherapy.
AB  - In this work we investigate a mathematical model describing tumour growth under a
      treatment by chemotherapy that incorporates time-delay related to the conversion
      from resting to hunting cells. We study the model using values for the parameters
      according to experimental results and vary some parameters relevant to the
      treatment of cancer. We find that our model exhibits a dynamical behaviour
      associated with the suppression of cancer cells, when either continuous or pulsed
      chemotherapy is applied according to clinical protocols, for a large range of
      relevant parameters. When the chemotherapy is successful, the predation
      coefficient of the chemotherapic agent acting on cancer cells varies with the
      infusion rate of chemotherapy according to an inverse relation. Finally, our
      model was able to reproduce the experimental results obtained by Michor and
      collaborators [Nature 435 (2005) 1267] about the exponential decline of cancer
      cells when patients are treated with the drug glivec. 

PMID- 24333155
TI  - Changes in sugar content and proteome of potato in response to cold and
      dehydration stress and their implications for cryopreservation.
AB  - The key to successful cryopreservation lies in the induction of tolerance towards
      dehydration/desiccation and freezing. The accumulation of osmo-active compounds,
      which can be induced by drought and cold stress, is therefore important. In the
      present study, three-week old shoots from in vitro plantlets of the cultivated
      potato Solanum tuberosum and its frost-resistant relative Solanum commersonii
      were submitted to osmotic stress (by using sucrose) and chilling (6 degrees C).
      After 14days of exposure, shoot tips were sampled in order to gain an insight
      into changes of the proteome and soluble sugars. Also, the effect of these
      treatments on growth performance behaviour and on the success of cryopreservation
      was evaluated. Identified proteins that changed in abundance due to stress were
      associated with stress response. Additionally, carbohydrate analyses in both
      species, after exposure to chilling, also indicated species-related differences;
      this observation could point towards a better-adapted physiological state of the
      donor plants of S. commersonii prior to the cryoprocedure and therefore a better
      recovery of the meristems. BIOLOGICAL SIGNIFICANCE: To our knowledge, this is the
      first study in which cryopreservation experiments are combined with the
      observation of the responses to abiotic stress exposure involving the potato
      species S. commersonii and S. tuberosum. These two species are known to have a
      different cold-acclimation behaviour, which seems to be closely related to their
      tolerance towards cryopreservation. Furthermore, common and differential
      responses to abiotic stresses were observed in the two species indicating that
      some pathways could be crucial not only in the plant's response to stress but
      also in tolerance towards cryopreservation.

PMID- 24333156
TI  - Proteomic analysis of peach fruit during ripening upon post-harvest heat combined
      with 1-MCP treatment.
AB  - Regulation of peach fruit ripening by heat combined with 1-Methylcyclopropene (1
      MCP) was studied by 2-dimensional gel electrophoresis (2-DE) and Matrix-Assisted
      Laser Desorption/Ionization Time of Flight tandem Mass Spectrometry (MALDI
      TOF/TOF). Proteins from peach fruits after harvest (CK) and treated by heat
      combined with 1-MCP (HM) were then stored at room temperature for 0, 1, 3 and
      5days. Among the identified 42 protein spots, the differential abundant proteins
      belonged to pathways of defense and response (35.71%), energy and metabolism
      (30.95%), ripening and senescence (14.29%), cell structure (14.29%) and protein
      fate (4.76%). Compared with separate heat or 1-MCP treatment, pectinesterase
      inhibitor (PEI) and heat shock protein (HSP) appeared, and abscisic stress
      ripening-like protein (ASR) disappeared after the treatment, while HM
      specifically increased the abundances of glutathione peroxidase (GPX),
      peroxiredoxin, calmodulin, and decreased those of cytosolic malate dehydrogenase,
      d-3-phosphoglycerate dehydrogenase (GAPDH) and glutamine synthetase. HM treatment
      protected fruit cells by enhancing the capabilities of stress response and
      defense, inhibiting substance and energy metabolism, limiting cell calcium loss.
      The results suggest that the self-defense capability of peach fruit was boosted
      by HM treatment. This study is informative in exploring the influences of HM on
      peach fruit ripening by demonstrating that 1-MCP and heat functioned
      synergistically. BIOLOGICAL SIGNIFICANCE: To analyze the functions of
      differentially expressed proteins and to elucidate the response of early-maturing
      melting peach fruit (cv. Huiyulu) during ripening, we herein, for the first time,
      studied the effects of HM treatment on involved protein profiles by a proteomic
      approach with 2-DE and MALDI-TOF/TOF. This study successfully verified that HM
      functioned synergistically rather than simply superimposed on the proteome level.
      In addition, this study explains the molecular mechanism regarding peach fruit
      development and ripening on the proteome level, offers new insights into relevant
      physiological mechanism, and provides theoretical evidence for reinforcing
      quality control of post-harvest peach fruit in practice.

PMID- 24333158
TI  - Pediatric misophonia with comorbid obsessive-compulsive spectrum disorders.
AB  - OBJECTIVE: Misophonia is a potentially debilitating condition characterized by
      increased sensitivity to specific sounds, which cause subsequent behavioral and
      emotional responses. The nature, clinical phenomenology and etiology of
      misophonia remain unclear, and misophonic clinical presentations are not
      currently accounted for by existing psychiatric or audiological disorders.
      METHOD: We present a case of pediatric misophonia in the context of comorbid
      obsessive-compulsive disorder and Tourette's syndrome. RESULTS: Given the
      interrelationships among obsessive-compulsive spectrum disorders and misophonia,
      these disorders may share underlying pathophysiology, particularly within the
      dopaminergic and serotonergic neural systems. Clinical (i.e., treatment) and
      theoretical implications are discussed.

PMID- 24333157
TI  - Integrated medical care management and behavioral risk factor reduction for
      multicondition patients: behavioral outcomes of the TEAMcare trial.
AB  - PURPOSE: The purpose of the study was to compare behavioral outcomes (physical
      activity, sedentary behavior, smoking cessation, diet) between the intervention
      and usual care conditions from the TEAMcare trial. METHODS: TEAMcare was a
      randomized trial among 214 adults with depression and poorly controlled diabetes
      and/or coronary heart disease that promoted health behavior change and
      pharmacotherapy to improve health. Behavioral outcomes were measured with the
      International Physical Activity Questionnaire (physical activity, sitting time)
      and the Summary of Diabetes Self-Care Activities Measure (smoking, diet,
      exercise). Poisson regression models among completers (N=185) were conducted
      adjusting for age, education, smoking status and depression. RESULTS:
      Intervention participants had more days/week following a healthy eating plan
      [relative rate=1.2, 95% confidence interval (CI)=1.1-1.4] and more days of
      participation in 30 min of physical activity (relative rate=1.2, 95% CI=1.1-2.0)
      compared to usual care. Intervention participants were more likely to meet
      physical activity guidelines (7.5% increase) compared to usual care (12%
      decrease; P=.053). CONCLUSION: Diet and activity generally improved for those
      receiving the intervention, while there were no differences in some aspects of
      diet (fruit and vegetable and high-fat food intake), smoking status and sitting
      time between conditions in the TEAMcare trial.

PMID- 24333159
TI  - A model of teneral dehydration in Glossina.
AB  - The results of a long-established investigation into teneral transpiration are
      used as a rudimentary data set. These data are not complete in that all are at 25
      degrees C and the temperature-dependence cannot, therefore, be resolved. An
      allowance is, nonetheless, made for the outstanding temperature-dependent data.
      The data are generalised to all humidities, levels of activity and, in theory,
      temperatures, by invoking the property of multiplicative separability. In this
      way a formulation, which is a very simple, first order, ordinary differential
      equation, is devised. The model is extended to include a variety of Glossina
      species by resorting to their relative, resting water loss rates in dry air. The
      calculated, total water loss is converted to the relevant humidity, at 24 degrees
      C, that which produced an equivalent water loss in the pupa, in order to exploit
      an adaption of an established survival relationship. The resulting computational
      model calculates total, teneral water loss, consequent mortality and adult
      recruitment. Surprisingly, the postulated race against time, to feed, applies
      more to the mesophilic and xerophilic species, in that increasing order. So much
      so that it is reasonable to conclude that, should Glossina brevipalpis survive
      the pupal phase, it will almost certainly survive to locate a host, without there
      being any significant prospect of death from dehydration. With the conclusion of
      this work comes the revelation that the classification of species as hygrophilic,
      mesophilic and xerophilic is largely true only in so much as their third and
      fourth instars are and, possibly, the hours shortly before eclosion. 

PMID- 24333160
TI  - Altered gut microbiota and activity in a murine model of autism spectrum
      disorders.
AB  - Autism spectrum disorder (ASD) is a heterogeneous group of complex
      neurodevelopmental disorders with evidence of genetic predisposition. Intestinal
      disturbances are reported in ASD patients and compositional changes in gut
      microbiota are described. However, the role of microbiota in brain disorders is
      poorly documented. Here, we used a murine model of ASD to investigate the
      relation between gut microbiota and autism-like behaviour. Using next generation
      sequencing technology, microbiota composition was investigated in mice in utero
      exposed to valproic acid (VPA). Moreover, levels of short chain fatty acids
      (SCFA) and lactic acid in caecal content were determined. Our data demonstrate a
      transgenerational impact of in utero VPA exposure on gut microbiota in the
      offspring. Prenatal VPA exposure affected operational taxonomic units (OTUs)
      assigned to genera within the main phyla of Bacteroidetes and Firmicutes and the
      order of Desulfovibrionales, corroborating human ASD studies. In addition, OTUs
      assigned to genera of Alistipes, Enterorhabdus, Mollicutes and Erysipelotrichalis
      were especially associated with male VPA-exposed offspring. The microbial
      differences of VPA in utero-exposed males deviated from those observed in females
      and was (i) positively associated with increased levels of caecal butyrate as
      well as ileal neutrophil infiltration and (ii) inversely associated with
      intestinal levels of serotonin and social behaviour scores. These findings show
      that autism-like behaviour and its intestinal phenotype is associated with
      altered microbial colonization and activity in a murine model for ASD, with
      preponderance in male offspring. These results open new avenues in the scientific
      trajectory of managing neurodevelopmental disorders by gut microbiome modulation.

PMID- 24333161
TI  - Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin
      dependent manner? In vitro, in vivo and clinical studies.
AB  - Ascorbate (Asc) has been shown to increase nitric oxide (NO) bioavailability and
      thereby improve endothelial function in patients showing signs of endothelial
      dysfunction. Tetrahydrobiopterin (BH4) is a co-factor of endothelial nitric oxide
      synthase (eNOS) which may easily become oxidized to the inactive form
      dihydrobiopterin (BH2). Asc may increase NO bioavailability by a number of
      mechanisms involving BH4 and eNOS. Asc increases BH4 bioavailability by either
      reducing oxidized BH4 or preventing BH4 from becoming oxidized in the first
      place. Asc could also increase NO bioavailability in a BH4-independent manner by
      increasing eNOS activity by changing its phosphorylation and S-nitrosylation
      status or by upregulating eNOS expression. In this review, we discuss the
      putative mechanisms by which Asc may increase NO bioavailability through its
      interactions with BH4 and eNOS.

PMID- 24333162
TI  - Low concentration of exogenous carbon monoxide protects mammalian cells against
      proliferation induced by radiation-induced bystander effect.
AB  - Radiation-induced bystander effect (RIBE) has been proposed to have tight
      relationship with the irradiation-caused secondary cancers beyond the irradiation
      treated area after radiotherapy. Our previous studies demonstrated a protective
      effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE
      after alpha-particle irradiation. In the present work, a significant inhibitory
      effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II)
      dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and
      chromosome aberration was observed. Further studies on the mechanism revealed
      that the transforming growth factor beta1/nitric oxide (NO) signaling pathway,
      which mediated RIBE signaling transduction, could be modulated by CO involved in
      the protective effects. Considering the potential of exogenous CO in clinical
      applications and its protective effect on RIBE, the present work aims to provide
      a foundation for potential application of CO in radiotherapy.

PMID- 24333163
TI  - Reconstructed mung bean trypsin inhibitor targeting cell surface GRP78 induces
      apoptosis and inhibits tumor growth in colorectal cancer.
AB  - Glucose regulated protein 78 (GRP78) has been reported to be present on cell
      membranes of cancer cells but not the normal cells, serving as a potential anti
      cancer target. In the present study, a fusion protein containing the GRP78
      binding peptide WIFPWIQL and the active fragment of mung bean trypsin inhibitor
      was constructed, and its targeted anti-tumor effects were investigated both in
      vitro and in vivo. The results showed that the fusion protein specifically
      inhibited growth and induced apoptosis in colorectal cancer cells but not in the
      normal cells. Mechanistically, these anti-tumor effects were attributed to
      induction of G1 phase arrest and activation of multiple apoptotic pathways.
      Importantly, the fusion protein could also suppress the growth of xenografted
      human colorectal carcinoma in vivo. Our study reveals that this fusion protein
      may be developed as a therapeutic agent for treatment of colon cancer, and holds
      important implications for developing other anti-cancer peptide drugs. 

PMID- 24333166
TI  - Early markers of neural dysfunction and compensation: a model from minimal
      hepatic encephalopathy.
AB  - OBJECTIVE: The Inhibitory Control Task (ICT) was used to detect minimal hepatic
      encephalopathy (MHE). ICT assesses attention, working memory and inhibition by
      evaluating performance in detect, go and nogo trials, respectively. The event
      related potentials (ERPs) elicited by the ICT provide insight into neural
      mechanisms underlying the cognitive alterations associated with MHE. METHODS: The
      performance and the ERPs elicited by ICT were measured in 31 patients with
      cirrhosis (13 with and 18 without MHE) and in 17 controls. The latency and
      amplitude of the N2, P3a, P3b and nogo-P3 were compared among the groups.
      RESULTS: Patients with MHE performed worse in all ICT trials compared to patients
      without MHE and controls. Cirrhotic patients, both with and without MHE,
      displayed a reduction in P3a amplitude, selectively in the detect trials.
      Patients without MHE exhibited greater N2 and nogo-P3 amplitudes compared to
      patients with MHE and controls. CONCLUSIONS: Both patients with and without MHE
      displayed neural alterations reflecting attentional deficits (i.e., P3a
      attenuation). However, patients without MHE coped with such dysfunctions by
      recruiting compensatory neural mechanisms, as suggested by the enhancement of the
      nogo-P3 and N2 amplitudes coupled with a normal ICT performance. SIGNIFICANCE:
      The study suggests how initial brain dysfunction might be compensated for by
      recruitment of additional neurocognitive resources.

PMID- 24333167
TI  - Sensorimotor communication in professional quartets.
AB  - Non-verbal group dynamics are often opaque to a formal quantitative analysis of
      communication flow. In this context, ensemble musicians can be a reliable model
      of expert group coordination. In fact, bodily motion is a critical component of
      inter-musician coordination and thus could be used as a valuable index of
      sensorimotor communication. Here we measured head movement kinematics of an
      expert quartet of musicians and, by applying Granger Causality analysis, we
      numerically described the causality patterns between participants. We found a
      clear positive relationship between the amount of communication and complexity of
      the score segment. Furthermore, we also applied temporal and dynamical changes to
      the musical score, known by the first violin only. The perturbations were devised
      in order to force unidirectional communication between the leader of the quartet
      and the other participants. Results show that in these situations, unidirectional
      influence from the leader decreased, thus implying that effective leadership may
      require prior sharing of information between participants. In conclusion, we
      could measure the amount of information flow and sensorimotor group dynamics
      suggesting that the fabric of leadership is not built upon exclusive information
      knowledge but rather on sharing it. 

PMID- 24333168
TI  - What might have been? The role of the ventromedial prefrontal cortex and lateral
      orbitofrontal cortex in counterfactual emotions and choice.
AB  - Counterfactual feelings of regret occur when people make comparisons between an
      actual outcome and a better outcome that would have occurred under a different
      choice. We investigated the choices of individuals with damage to the ventral
      medial prefrontal cortex (VMPFC) and the lateral orbital frontal cortex (LOFC) to
      see whether their emotional responses were sensitive to regret. Participants made
      choices between gambles, each with monetary outcomes. After every choice,
      subjects learned the consequences of both gambles and rated their emotional
      response to the outcome. Normal subjects and lesion control subjects tended to
      make better choices and reported post-decision emotions that were sensitive to
      regret comparisons. VMPFC patients tended to make worse choices, and, contrary to
      our predictions, they reported emotions that were sensitive to regret
      comparisons. In contrast, LOFC patients made better choices, but reported
      emotional reactions that were insensitive to regret comparisons. We suggest the
      VMPFC is involved in the association between choices and anticipated emotions
      that guide future choices, while the LOFC is involved in experienced emotions
      that follow choices, emotions that may signal the need for behavioral change. 

PMID- 24333164
TI  - STRIPAK complexes: structure, biological function, and involvement in human
      diseases.
AB  - The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear
      autoantigen, and zinedin. Striatin family members have no intrinsic catalytic
      activity, but rather function as scaffolding proteins. Remarkably, they organize
      multiple diverse, large signaling complexes that participate in a variety of
      cellular processes. Moreover, they appear to be regulatory/targeting subunits for
      the major eukaryotic serine/threonine protein phosphatase 2A. In addition,
      striatin family members associate with germinal center kinase III kinases as well
      as other novel components, earning these assemblies the name striatin-interacting
      phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great
      increase in functional and mechanistic studies aimed at identifying and
      understanding the roles of STRIPAK and STRIPAK-like complexes in cellular
      processes of multiple organisms. These studies have identified novel STRIPAK and
      STRIPAK-like complexes and have explored their roles in specific signaling
      pathways. Together, the results of these studies have sparked increased interest
      in striatin family complexes because they have revealed roles in signaling, cell
      cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity,
      cell migration, neural and vascular development, and cardiac function. Moreover,
      STRIPAK complexes have been connected to clinical conditions, including cardiac
      disease, diabetes, autism, and cerebral cavernous malformation. In this review,
      we discuss the expression, localization, and protein domain structure of striatin
      family members. Then we consider the diverse complexes these proteins and their
      homologs form in various organisms, emphasizing what is known regarding function
      and regulation. Finally, we explore possible roles of striatin family complexes
      in disease, especially cerebral cavernous malformation. 

PMID- 24333170
TI  - Elevated serum soluble CD200 and CD200R as surrogate markers of bone loss under
      bed rest conditions.
AB  - CD200 is a transmembrane protein that belongs to the immunoglobulin family of
      proteins and is ubiquitously expressed on a variety of cell types. Upon
      interaction with its receptors (CD200Rs) expressed on myeloid-derived cells and T
      lymphocytes, an immunoregulatory signal is delivered to receptor-expressing
      cells. Previous studies have implicated a role for CD200:CD200R in the regulation
      of the expression of mRNA markers of osteoclastogenesis/osteoblastogenesis,
      following interaction of CD200 (on osteoblast precursors) with CD200R1 (on
      osteoclast precursors). Signaling of CD200R1 is hypothesized to attenuate
      osteoclastogenesis. We have investigated whether levels of soluble forms of CD200
      and/or CD200R1 (sCD200, sCD200R1) are altered in volunteers undergoing 6 degrees 
      head down tilt bed rest to mimic conditions of microgravity known to be
      associated with preferential osteoclastogenesis and whether countermeasures,
      reported to be beneficial in attenuation of bone loss under microgravity
      conditions, would lead to altered sCD200 and sCD200R1 levels. Our data suggest
      that, as predicted, sCD200 levels fall under bed rest conditions while sCD200R1
      levels rise. In subjects undergoing 30-minute per day continuous centrifugation
      protocols, as a countermeasure to attenuate changes which may lead to bone loss,
      these alterations in sCD200 and sCD200R1 levels seen under conditions of bed rest
      were abolished or attenuated. Our results suggest that measurement of sCD200
      and/or sCD200R1 may prove a useful and rapid means of monitoring subjects at risk
      of bone loss and/or accessing the efficacy of treatment regimes designed to
      counter bone loss. 

PMID- 24333171
TI  - Estrogen receptor alpha in osteocytes regulates trabecular bone formation in
      female mice.
AB  - Estrogens are well known steroid hormones necessary to maintain bone health. In
      addition, mechanical loading, in which estrogen signaling may intersect with the
      Wnt/beta-catenin pathway, is essential for bone maintenance. As osteocytes are
      known as the major mechanosensory cells embedded in mineralized bone matrix,
      osteocyte ERalpha deletion mice (ERalpha(DeltaOcy/DeltaOcy)) were generated by
      mating ERalpha floxed mice with Dmp1-Cre mice to determine the role of ERalpha in
      osteocytes. Trabecular bone mineral density of female, but not male
      ERalpha(DeltaOcy/DeltaOcy) mice was significantly decreased. Bone formation
      parameters in ERalpha(DeltaOcy/DeltaOcy) were significantly decreased while
      osteoclast parameters were unchanged. This suggests that ERalpha in osteocytes
      exerts osteoprotective function by positively controlling bone formation. To
      identify potential targets of ERalpha, gene array analysis of Dmp1-GFP osteocytes
      sorted by FACS from ERalpha(DeltaOcy/DeltaOcy) and control mice was performed.
      Gene expression microarray followed by gene ontology analyses revealed that
      osteocytes from ERalpha(DeltaOcy/DeltaOcy) highly expressed genes categorized in
      'Secreted' when compared to control osteocytes. Among them, expression of Mdk and
      Sostdc1, both of which are Wnt inhibitors, was significantly increased without
      alteration of expression of the mature osteocyte markers such as Sost and beta
      catenin. Moreover, hindlimb suspension experiments showed that trabecular bone
      loss due to unloading was greater in ERalpha(DeltaOcy/DeltaOcy) mice without
      cortical bone loss. These data suggest that ERalpha in osteocytes has
      osteoprotective functions in trabecular bone formation through regulating
      expression of Wnt antagonists, but conversely plays a negative role in cortical
      bone loss due to unloading. 

PMID- 24333172
TI  - Association analysis of a functional variant in ATXN2 with schizophrenia.
AB  - Schizophrenia (SZ) is a severe mental disorder characterized by multiple
      neurodevelopmental dysfunctions including a breakdown of thinking process and a
      deficit of typical emotional responses. Ataxin-2 (ATXN2) plays vital roles in
      cell proliferation and growth, and functional mutations of ATXN2 cause
      neurodegenerative phenotypes, including spinocerebellar ataxia type 2 (SCA2) and
      amyotrophic lateral sclerosis (ALS). To explore the possible role of ATXN2 in SZ,
      we conducted a two-stage study to examine the association of ATXN2 polymorphisms
      with SZ in the Han Chinese population. Association analysis of seven SNPs in 768
      patients and 1348 controls revealed two associated SNPs, including rs630511
      (P=1.76E-4) and rs7969300 (P=5.08E-4). We examined these two SNPs in a validation
      sample of 1957 patients and 1509 controls, and observed an association of
      rs7969300 with SZ (P=5.03E-3). The SNP rs7969300 is a non-synonymous SNP causing
      a Ser to Asn substitution, which is predicted to increase the protein stability
      of ATXN2. Our data suggest that the ATXN2 gene may confer vulnerability for SZ,
      adding further evidence for the genetic variants within the developmental pathway
      in the illness.

PMID- 24333173
TI  - Repeated exposure to propofol impairs spatial learning, inhibits LTP and reduces
      CaMKIIalpha in young rats.
AB  - Propofol is one of the most widely used intravenous anesthetics. We investigated
      the effects of propofol injected during development on synaptic plasticity and
      long-term spatial learning and memory in young rats. Propofol (75 mg/kg) was
      administered to 7-day-old rats either as a single dose or in 7 doses at 24-h
      intervals. At postnatal day 28, spatial learning in the Morris water maze and
      long-term potentiation (LTP) in the CA1 region of the hippocampus were
      significantly reduced in the rats that had received 7 doses of propofol. This
      treatment also significantly decreased the expression of CaMKIIalpha and
      pCaMKIIalpha in the hippocampus, and reduced the pCaMKIIalpha/CaMKIIalpha ratio,
      as measured by immunochemistry and Western blotting. We conclude that repeated
      exposure to propofol impairs learning and memory in the developing rat brain, and
      this finding may be associated with down-regulation of CaMKIIalpha and
      pCaMKIIalpha.

PMID- 24333175
TI  - Efferent-mediated reduction in cochlear gain does not alter tuning estimates from
      stimulus-frequency otoacoustic emission group delays.
AB  - The existence of efferent feedback from cortical and subcortical brain centers to
      the hair cells of the cochlea has been recognized for many years, but the role
      that efferent neurons play in hearing is not completely known. Stimulation of
      medial olivocochlear (MOC) efferent neurons suppresses sound-evoked basilar
      membrane responses and changes the tuning of single auditory nerve fibers in
      animal models. Both of these effects are linked to a MOC-induced reduction in the
      gain of the cochlear amplification provided by outer hair cells. To non
      invasively examine the link between cochlear suppression and tuning in humans,
      stimulus-frequency otoacoustic emissions (SFOAEs) were recorded in conditions
      with and without contralateral acoustic stimulation (CAS) from 28 normal-hearing
      participants. SFOAEs were measured using clusters of closely-spaced probe-tone
      frequencies centered near 1.4 and 2.0kHz. An index of cochlear tuning, QERB, was
      calculated based on measures of SFOAE group delay at both 1.4 and 2.0kHz. A
      statistically significant (p<0.01) decrease in SFOAE levels acquired during CAS
      was detected only for the SFOAE cluster centered at 2kHz. No statistically
      significant differences in QERB were found between conditions with and without
      CAS at 1.4 and 2.0kHz. These findings suggest that in humans, tuning based on
      SFOAE group delay estimates is not appreciably altered at cochlear locations with
      MOC efferent-induced reductions in cochlear gain. 

PMID- 24333174
TI  - Amelioration of improper differentiation of somatostatin-positive interneurons by
      triiodothyronine in a growth-retarded hypothyroid mouse strain.
AB  - Thyroid hormone (TH) plays an important role in brain development, and TH
      deficiency during pregnancy or early postnatal periods leads to neurological
      disorders such as cretinism. Hypothyroidism reduces the number of parvalbumin
      (PV)-positive interneurons in the neocortex and hippocampus. Here we used a mouse
      strain (growth-retarded; grt) that shows growth retardation and hypothyroidism to
      examine whether somatostatin (Sst)-positive interneurons that are generated from
      the same pool of neural progenitor cells as PV-positive cells are also altered by
      TH deficiency. The number of PV-positive interneurons was significantly decreased
      in the neocortex and hippocampus of grt mice as compared with normal control
      mice. In contrast to the decrease in the number of PV neurons, the number of Sst
      positive interneurons in grt mice was increased in the stratum oriens of the
      hippocampus and the hilus of the dentate gyrus, although their number was
      unchanged in the neocortex. These changes were reversed by triiodothyronine
      administration from postnatal day (PD) 0 to 20. TH supplementation that was
      initiated after PD21 did not, however, affect the number of PV- or Sst-positive
      cells. These results suggest that during the first three postnatal weeks, TH may
      be critical for the generation of subpopulations of interneurons. 

PMID- 24333169
TI  - Clinical application of transcriptional activators of bile salt transporters.
AB  - Hepatobiliary bile salt (BS) transporters are critical determinants of BS
      homeostasis controlling intracellular concentrations of BSs and their
      enterohepatic circulation. Genetic or acquired dysfunction of specific transport
      systems causes intrahepatic and systemic retention of potentially cytotoxic BSs,
      which, in high concentrations, may disturb integrity of cell membranes and
      subcellular organelles resulting in cell death, inflammation and fibrosis.
      Transcriptional regulation of canalicular BS efflux through bile salt export pump
      (BSEP), basolateral elimination through organic solute transporters alpha and
      beta (OSTalpha/OSTbeta) as well as inhibition of hepatocellular BS uptake through
      basolateral Na(+)-taurocholate cotransporting polypeptide (NTCP) represent
      critical steps in protection from hepatocellular BS overload and can be targeted
      therapeutically. In this article, we review the potential clinical implications
      of the major BS transporters BSEP, OSTalpha/OSTbeta and NTCP in the pathogenesis
      of hereditary and acquired cholestatic syndromes, provide an overview on
      transcriptional control of these transporters by the key regulatory nuclear
      receptors and discuss the potential therapeutic role of novel transcriptional
      activators of BS transporters in cholestasis. 

PMID- 24333176
TI  - Spatiotemporal development of the embryonic nervous system of Saccoglossus
      kowalevskii.
AB  - Defining the organization and temporal onset of key steps in neurogenesis in
      invertebrate deuterostomes is critical to understand the evolution of the
      bilaterian and deuterostome nervous systems. Although recent studies have
      revealed the organization of the nervous system in adult hemichordates, little
      attention has been paid to neurogenesis during embryonic development in this
      third major phylum of deuterostomes. We examine the early events of neural
      development in the enteropneust hemichordate Saccoglossus kowalevskii by
      analyzing the expression of 11 orthologs of key genes associated with
      neurogenesis in an expansive range of bilaterians. Using in situ hybridization
      (ISH) and RT-PCR, we follow the course of neural development to track the
      transition of the early embryonic diffuse nervous system to the more regionalized
      midline nervous system of the adult. We show that in Saccoglossus, neural
      progenitor markers are expressed maternally and broadly encircle the developing
      embryo. An increase in their expression and the onset of pan neural markers,
      indicate that neural specification occurs in late blastulae - early gastrulae. By
      mid-gastrulation, punctate expression of markers of differentiating neurons
      encircling the embryo indicate the presence of immature neurons, and at the end
      of gastrulation when the embryo begins to elongate, markers of mature neurons are
      expressed. At this stage, expression of a subset of neuronal markers is
      concentrated along the trunk ventral and dorsal midlines. These data indicate
      that the diffuse embryonic nervous system of Saccoglossus is transient and
      quickly reorganizes before hatching to resemble the adult regionalized,
      centralized nervous system. This regionalization occurs at a much earlier
      developmental stage than anticipated indicating that centralization is not linked
      in S. kowalevskii to a lifestyle change of a swimming larva metamorphosing to a
      crawling worm-like adult. 

PMID- 24333177
TI  - asunder is required for dynein localization and dorsal fate determination during
      Drosophila oogenesis.
AB  - We previously showed that asunder (asun) is a critical regulator of dynein
      localization during Drosophila spermatogenesis. Because the expression of asun is
      much higher in Drosophila ovaries and early embryos than in testes, we herein
      sought to determine whether ASUN plays roles in oogenesis and/or embryogenesis.
      We characterized the female germline phenotypes of flies homozygous for a null
      allele of asun (asun(d93)). We find that asun(d93) females lay very few eggs and
      contain smaller ovaries with a highly disorganized arrangement of ovarioles in
      comparison to wild-type females. asun(d93) ovaries also contain a significant
      number of egg chambers with structural defects. A majority of the eggs laid by
      asun(d93) females are ventralized to varying degrees, from mild to severe; this
      ventralization phenotype may be secondary to defective localization of gurken
      transcripts, a dynein-regulated step, within asun(d93) oocytes. We find that
      dynein localization is aberrant in asun(d93) oocytes, indicating that ASUN is
      required for this process in both male and female germ cells. In addition to the
      loss of gurken mRNA localization, asun(d93) ovaries exhibit defects in other
      dynein-mediated processes such as migration of nurse cell centrosomes into the
      oocyte during the early mitotic divisions, maintenance of the oocyte nucleus in
      the anterior-dorsal region of the oocyte in late-stage egg chambers, and coupling
      between the oocyte nucleus and centrosomes. Taken together, our data indicate
      that asun is a critical regulator of dynein localization and dynein-mediated
      processes during Drosophila oogenesis. 

PMID- 24333179
TI  - Post-transcriptional regulation of wnt8a is essential to zebrafish axis
      development.
AB  - wnt8a Is essential for normal patterning during vertebrate embryonic development,
      and either gain or loss-of-function gene dysregulation results in severe axis
      malformations. The zebrafish wnt8a locus is structured such that transcripts may
      possess two regulatory 3' untranslated regions (UTRs), raising the possibility of
      post-transcriptional regulation as an important mode of wnt8a signaling control.
      To determine whether both UTRs contribute to post-transcriptional wnt8a gene
      regulation, each UTR (UTR1 and UTR2) was tested in transient and transgenic
      reporter assays. Both UTRs suppress EGFP reporter expression in cis, with UTR2
      exhibiting a more pronounced effect. UTR2 contains a 6 base sequence necessary
      for UTR2 regulatory function that is complementary to the seed of the microRNA,
      miR-430. A target protector morpholino that overlaps the seed complement
      stabilizes both reporter mRNAs and wnt8a mRNAs, and produces phenotypic
      abnormalities consistent with wnt8a gain-of-function. In rescue assays, specific
      functions can be attributed to each of the two wnt8a proteins encoded by the
      locus. An interplay of wnt8a.1 and wnt8a.2 regulates neural and mesodermal
      patterning and morphogenesis as well as patterning between brain subdivisions.
      Thus, post-transcriptional control of wnt8a is essential to fine tune the balance
      of the signaling outputs of the complex wnt8a locus. 

PMID- 24333178
TI  - FGF signaling is required for brain left-right asymmetry and brain midline
      formation.
AB  - Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the
      embryo. Here we uncover a role for FGF signaling that specifically disrupts brain
      asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF
      signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM
      markers southpaw and lefty2 are not affected. However, asymmetrically expressed
      brain markers lefty1 and cyclops become bilateral. We show that FGF signaling
      controls expression of six3b and six7, two transcription factors required for
      repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC
      (aPKC) and beta-catenin protein distribution revealed a midline structure in the
      forebrain that is dependent on a balance of FGF signaling. Ectopic activation of
      FGF signaling leads to overexpression of six3b, loss of organized midline
      adherins junctions and bilateral loss of lefty1 expression. Reducing FGF
      signaling leads to a reduction in six3b and six7 expression, an increase in cell
      boundary formation in the brain midline, and bilateral expression of lefty1.
      Together, these results suggest a novel role for FGF signaling in the brain to
      control LR asymmetry, six transcription factor expressions, and a midline barrier
      structure. 

PMID- 24333180
TI  - Hox transcription factor Antp regulates sericin-1 gene expression in the terminal
      differentiated silk gland of Bombyx mori.
AB  - Hox genes are well-known master regulators in developmental morphogenesis along
      the anteroposterior axis of animals. However, the molecular mechanisms by which
      Hox proteins regulate their target genes and determine cell fates are not fully
      understood. The silk gland of Bombyx mori is a tubular tissue divided into
      several subparts along the anteroposterior axis, and the silk genes are expressed
      with specific patterns. The sericin-1 gene (ser1) is expressed in the middle silk
      gland (MSG) with sublocal specificity. Here we show that the Hox protein Antp is
      a component of the middle silk gland-specific complex, MIC (MSG-intermolt
      specific complex), binds to the essential promoter element of ser1, and activates
      its expression. Ectopic expression of Antp in transgenic silkworms induced the
      expression of ser1 in the posterior silk gland (PSG), but not in the anterior
      part of MSG (MSG-A). Correspondingly, a MIC-like complex was formed by the
      addition of recombinant Antp in extracts from PSG with its cofactors Exd and Hth,
      but not in extracts from MSG-A. Splicing patterns of ser1 mRNA induced by the
      ectopic expression of Antp in PSG were almost the same as those in MSG at the
      fifth instar and altered depending on the induction timing of Antp. Other Hox
      genes were expressed with sublocal specificity in the silk gland. The Bombyx silk
      gland might provide a useful system for understanding how Hox proteins select and
      regulate their target genes. 

PMID- 24333181
TI  - Sulfatide epigenetically regulates miR-223 and promotes the migration of human
      hepatocellular carcinoma cells.
AB  - BACKGROUND & AIMS: The biological relevance and regulation mechanism of aberrant
      miR-223 expression in human hepatocellular carcinoma (HCC) remain unknown. Our
      aim was to investigate miR-223 regulation in HCC. METHODS: miR-223 and integrin
      alphaV dysregulation were verified in 57 HCC specimens. Immunohistochemical
      analysis of integrin alphaV and sulfatide levels was performed on another cohort
      of 103 HCC samples. Epigenetic analysis was used to explore the effect of
      sulfatide on miR-223 transcription. Orthotopic growth, and intrahepatic and
      pulmonary metastasis of tumors derived from SMMC-7721 cells expressing miR-223 or
      cerebroside sulfotransferase were monitored in mice. RESULTS: miR-223 was reduced
      in HCC specimens and highly metastatic cell lines. Enhanced miR-223 expression
      had a negative effect on integrin alphaV-mediated cell migration. In vivo assays
      of metastasis in an orthotopically implanted model demonstrated that miR-223
      effectively inhibited HCC metastasis. Further analysis demonstrated that integrin
      alphaV is negatively regulated by miR-223. Moreover, the integrin alphaV subunit
      was significantly positively correlated with highly expressed sulfatide in 103
      HCC specimens. Intriguingly, miR-223 expression was suppressed by sulfatide in
      HCC in association with reduced recruitment of acetylated histone H3 and
      C/EBPalpha to the pre-miR-223 gene promoter, where monocytic leukemia zinc finger
      (MOZ) protein, a MYST-type histone acetyltransferase, lost its attachment. The
      expression of histone deacetylases, HDAC9 and HDAC10, were greatly stimulated by
      sulfatide and their recruitment to miR-223 gene promoter was enhanced.
      CONCLUSIONS: Downregulation of miR-223 in HCC is associated with the epigenetic
      regulation by highly expressed sulfatide and involved in tumor metastasis.

PMID- 24333182
TI  - Hepatic steatosis exacerbated by endoplasmic reticulum stress-mediated
      downregulation of FXR in aging mice.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is characterized by
      an increase in hepatic triglyceride (TG) contents. The prevalence of NAFLD is
      increased with aging. However, the molecular mechanism for aging-induced fatty
      liver remains poorly understood. METHODS: Hepatic TG contents and gene expression
      profiles were analyzed in body weight-matched young (2 months), middle (8 months)
      and old (18 months) C57BL/6 mice. Endoplasmic reticulum (ER) stress and farnesoid
      X receptor (FXR) expression were examined. The mechanism of ER stress activation
      in the regulation of FXR expression was further investigated. RESULTS: In the
      present study, we found that TG was markedly accumulated and lipogenic genes were
      up-regulated in the liver of C57BL/6 mice aged 18 months. FXR, a key regulator of
      hepatic lipid metabolism was down-regulated in these old mice. At molecular
      levels, ER stress was activated in old mice and repressed FXR expression through
      inhibition of hepatocyte nuclear factor 1 alpha (HNF1alpha) transcriptional
      activity. CONCLUSIONS: Our findings demonstrate that FXR down-regulation plays a
      critical role in aging-induced fatty liver.

PMID- 24333184
TI  - Minimal impact of sofosbuvir and ribavirin on health related quality of life in
      chronic hepatitis C (CH-C).
AB  - BACKGROUND & AIMS: Treatment for CH-C contains interferon with substantial
      associated side effects and health-related quality of life (HRQL) impairment.
      Currently, there is no published data assessing the impact of interferon-free
      regimens on HRQL. The aim is to report the HRQL of patients who participated in
      clinical trials of sofosbuvir (SOF) for CH-C. METHODS: CH-C patients were treated
      with sofosbuvir (SOF), pegylated interferon (PegIFN), ribavirin (RBV), or placebo
      in different combinations and duration (POSITRON, FISSION, FUSION, and NEUTRINO
      phase III trials). HRQL was assessed using SF-36 at baseline, during treatment,
      at the end of treatment, and at follow-up, and compared between treatment arms.
      RESULTS: HRQL scores decreased over the course of treatment for all treatment
      arms in all studies; however, patients returned to their baseline score by the
      end of follow-up. Compared to placebo, SOF and RBV was not associated with HRQL
      impairment (POSITRON). Compared to SOF and RBV, HRQL was significantly more
      impaired in the PegIFN and RBV arm (FISSION). For those treated with SOF and RBV,
      there was no difference in HRQL between 12 weeks or 16 weeks of treatment
      (FUSION). Multivariate analysis demonstrated that depression, fatigue, and
      insomnia were important predictors of patients' HRQL prior, during or after
      treatment. Additionally, anemia and receiving interferon were predictors of HRQL
      impairment during treatment. Achieving sustained virologic response after 12
      weeks of follow-up (SVR-12) with SOF and RBV was associated with improvement in
      HRQL scores from baseline. CONCLUSIONS: Treatment-related HRQL impairment during
      SOF and RBV regimen is mild, and does not increase with longer treatment
      duration. Achieving SVR-12 with SOF and RBV is associated with an improvement in
      HRQL.

PMID- 24333183
TI  - A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in
      acute and chronic liver injury in the mouse.
AB  - BACKGROUND & AIMS: Neutrophils are important immune effectors required for
      sterile and non-sterile inflammatory responses. However, neutrophils are
      associated with pathology in drug-induced liver injury, acute alcoholic liver
      disease, and ischemia-reperfusion injury. An understanding of the complex
      mechanisms that control neutrophil recruitment to the injured liver is desirable
      for developing strategies aimed at limiting neutrophil-mediated cellular damage.
      METHODS: Wt, tlr2(-/-), tlr4(-/-), and s100a9(-/-) mice were administered CCl4
      either acutely (8, 24, 48, or 72 h) or chronically (8 weeks) and livers
      investigated by histological (IHC for neutrophils, fibrogenesis, proliferation,
      and chemotactic proteins) or molecular approaches (qRT-PCR for neutrophil
      chemoattractant chemokines and cytokines as well as pro-fibrogenic genes).
      RESULTS: Mice lacking TLR2 or S100A9 failed to recruit neutrophils to the injured
      liver and had a defective hepatic induction of the neutrophil chemokine CXCL-2.
      Hierarchy between TLR2 and S100A9 proved to be complex. While induction of S100A9
      was dependent on TLR2 in isolated neutrophils, there was a more complicated two
      way signalling cross-talk between TLR2 and S100A9 in whole liver. However, wound
      healing and regenerative responses of the liver were unaffected in these genetic
      backgrounds as well as in wild type mice, in which neutrophils were depleted by
      infusion of Ly-6G antibody. CONCLUSIONS: We have identified TLR2 and
      S100A8/S100A9 as key regulators of hepatic CXCL-2 expression and neutrophil
      recruitment. This novel TLR2-S100A9-CXCL-2 pathway may be of use in development
      of new strategies for selectively manipulating neutrophils in liver disease
      without impairing normal wound healing and regenerative responses.

PMID- 24333185
TI  - The effect of pharmacological PI3Kgamma inhibitor on eotaxin-induced human
      eosinophil functions.
AB  - BACKGROUND: Asthma is characterized by chronic inflammation caused by activation
      of immune cells including Th2 lymphocytes and eosinophils. Phosphoinositide 3
      kinase (PI3K) gamma deficient asthmatic mice did not develop lung eosinophilia,
      although the detailed mechanisms are not well known. A CC chemokine eotaxin
      (CCL11) plays a prominent role in developing eosinophilic inflammation through
      CCR3. In this study, we tested the roles of PI3Kgamma in eotaxin-induced
      eosinophil functions using a pharmacological inhibitor. METHOD: Human peripheral
      blood eosinophils were isolated by CD16-negative selection method. The effect of
      AS605240, synthetic PI3Kgamma inhibitor on eotaxin-induced adhesion, chemotaxis,
      and degranulation were studied using intracellular adhesion molecule-1 (ICAM-1)
      coated plates, Boyden chamber system, ELISA for eosinophil-derived neurotoxin
      (EDN) levels in the culture supernatant, respectively. CCR3 expression levels and
      extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were assessed
      by flowcytometry. Involvement of PI3Kgamma in spontaneous apoptosis was studied
      using flowcytometry. RESULTS: Although AS605240 did not affect the eosinophil
      spontaneous apoptosis, eotaxin-induced chemotaxis, adhesion to ICAM-1 coated
      plate, and EDN release were inhibited by AS605240. AS605240 also inhibited the
      eotaxin-induced ERK1/2 phosphorylation without down-regulation of surface CCR3
      expression. CONCLUSION: These results indicate that PI3Kgamma inhibitor
      attenuates eotaxin-induced eosinophil functions by suppressing the downstream
      signaling of CCR3 without significant cytotoxicity. PI3Kgamma plays an important
      role in the development of eosinophilic inflammation and blockade of PI3Kgamma
      might be a therapeutic strategy for treatment of eosinophil-related diseases
      including asthma.

PMID- 24333186
TI  - Effects of a FLAP inhibitor, GSK2190915, in asthmatics with high sputum
      neutrophils.
AB  - Patients with refractory asthma frequently have neutrophilic airway inflammation
      and respond poorly to inhaled corticosteroids. This study evaluated the effects
      of an oral 5-lipoxygenase-activating protein (FLAP) inhibitor, GSK2190915, in
      patients with asthma and elevated sputum neutrophils. Patients received 14 (range
      13-16) days treatment with GSK2190915 100 mg and placebo with a minimum 14 day
      washout in a double-blind, cross-over, randomised design (N = 14). Sputum
      induction was performed twice pre-dose in each treatment period to confirm sputum
      neutrophilia, and twice at the end of each treatment period. The primary endpoint
      was the percentage and absolute sputum neutrophil count, averaged for end-of
      treatment visits. GSK2190915 did not significantly reduce mean percentage sputum
      neutrophils (GSK2190915-placebo difference [95% CI]: -0.9 [-12.0, 10.3]), or mean
      sputum neutrophil counts (GSK2190915/placebo ratio [95% CI]: 1.06 [0.43, 2.61]).
      GSK2190915 resulted in a marked suppression (>90%) of sputum LTB4 and urine LTE4,
      but did not alter clinical endpoints. There were no safety issues. Despite
      suppressing the target mediator LTB4, FLAP inhibitor GSK2190915 had no short-term
      effect on sputum cell counts or clinical endpoints in patients with asthma and
      sputum neutrophilia.

PMID- 24333187
TI  - Characterization of a novel l-amino acid oxidase with protein oxidizing activity
      from Penicillium steckii AIU 027.
AB  - An enzyme exhibiting oxidase activity for beta-lactoglobulin, myoglobin, and l
      lysine-containing peptides was found from a newly isolated fungal strain,
      Penicillium steckii AIU 027. The enzyme also oxidized l-amino acids, N(alpha)
      benzyloxycarbonyl-l-lysine (N(alpha)-Z-l-lysine) and N(epsilon)-Z-l-lysine, but
      not d-amino acids and amines. Thus, the enzyme was classified into a group of l
      amino acid oxidases (l-AAOs). However, characteristics of this l-AAO were
      significantly different from those of other l-AAOs as follows. The l-AAO from P.
      steckii AIU 027 oxidized both the alpha-amino group and the epsilon-amino group
      in l-amino acids and l-lysine-containing peptides, and the Km values for l-lysine
      containing polypeptides were lower than those for N(alpha)-Z-l-lysine and l
      lysine-containing dipeptides. The enzyme contained flavin and iron, and composed
      of four identical subunits with molecular mass of 75.3 kDa. The N-terminal amino
      acid sequence, ENIADVADAMGPWFDGVAYMKSKKN, was different from that of other l
      AAOs. Thus, the l-AAO with protein oxidase activity was first reported here from
      P. steckii AIU 027. 

PMID- 24333188
TI  - Evaluation of baker's yeast strains exhibiting significant growth on Japanese
      beet molasses and compound analysis of the molasses types.
AB  - Cane molasses, most of which is imported, is used as a raw material for
      production of baker's yeast (Saccharomyces cerevisiae) in Japan. On the other
      hand, beet molasses is scarcely used for this purpose, but it can be of great
      advantage to cane molasses because it is domestically produced in relatively high
      amounts as a by-product of beet sugar processing. However, the yield of baker's
      yeast is sometimes low with Japanese beet molasses compared to imported cane
      molasses. For the production of baker's yeast with Japanese beet molasses, we
      evaluated S. cerevisiae strains, including industrial and laboratory strains, to
      group them according to the growth profile on beet and cane molasses. To discuss
      the factors affecting growth, we further analyzed the major compounds in both
      types of molasses. Beet molasses seems to contain compounds that promote the
      growth of beet molasses-favoring strains rather than inhibit the growth of cane
      molasses-favoring strains. It was assumed that alpha-amino acid was one of the
      growth promotion factors for beet molasses-favoring strains. 

PMID- 24333189
TI  - Androgen receptor identification in the diagnosis of eyelid sebaceous carcinomas.
AB  - PURPOSE: To assess the role of androgen receptor detection in diagnosing eyelid
      sebaceous carcinomas and to compare it with that of adipophilin. DESIGN:
      Retrospective, clinicopathologic study. METHODS: Ten sebaceous carcinomas (8
      invasive, 2 intraepithelial only) were stained immunohistochemically for androgen
      receptors and were compared with adipophilin staining. Receptor staining also was
      performed on benign sebaceous tumors (a sebaceoma and an adenoma) and as controls
      on eyelid basal cell carcinomas, eyelid squamous cell carcinomas, conjunctival
      squamous dysplasias, and conjunctival melanomas. RESULTS: All 8 patients with an
      invasive component of sebaceous carcinoma underwent a biopsy in which the tumor
      cells showed diffusely positive results for androgen receptors (>20% of cells and
      usually >40%) and positive results for adipophilin. Eight cases displaying an
      intraepithelial (or pagetoid) component of spread also showed diffusely positive
      results for androgen receptors and adipophilin in at least 1 of multiple biopsy
      samples from each patient. However, in 8 of 21 separate conjunctival biopsy
      specimens with intraepithelial cytologic atypia, adipophilin results were
      negative. A sebaceoma and a sebaceous adenoma also showed positive results for
      both of these biomarkers. Among the controls, squamous carcinomas and melanomas
      showed negative results for androgen receptors and adipophilin. Basal cell
      carcinomas displayed focal receptor positivity in fewer than 5% of cells and
      showed negative results for adipophilin. CONCLUSIONS: Androgen receptors and
      adipophilin can separate sebaceous tumors immunohistochemically from squamous
      carcinomas and melanomas, which showed negative results for both, and from basal
      cell carcinomas, which showed positive receptor results in a distant minority of
      cells. Regarding intraepithelial (or pagetoid) spread, androgen receptor
      detection was more sensitive and reliable than adipophilin in highlighting this
      component of the disease.

PMID- 24333190
TI  - Inflammatory responses in the rat superior colliculus after eye enucleation.
AB  - Ocular enucleation induces profound morphological alterations in central visual
      areas. However, little is known about the response of glial cells and possible
      inflammatory processes in visual brain areas resulting from eye enucleation. In
      this study, immunoblotting and immunostaining assays revealed increased
      expression of astrocyte and microglia markers in the rat superior colliculus (SC)
      between 1 and 15 days after contralateral enucleation. A transient increase of
      neuronal COX-2 protein expression was also found in the SC. To evaluate the role
      of an anti-inflammatory drug in attenuating both COX-2 and glial cell activation,
      the synthetic glucocorticoid dexamethasone (DEX) was administered (1 mg/kg i.p.,
      for 3 days) to enucleated rats. Immunoblotting data revealed that DEX treatment
      significantly inhibited COX-2 protein expression. Postlesion immunostaining for
      astrocyte and microglia markers was also significantly reduced by DEX treatment.
      These findings suggest that the removal of retinal ganglion cell input generates
      inflammatory responses in central retinorecipient structures.

PMID- 24333191
TI  - Increased expression of phosphorylated c-Jun and phosphorylated c-Jun N-terminal
      kinase associated with neuronal cell death in diabetic and high glucose exposed
      rat retinas.
AB  - The aim of this study is to examine whether the increased expression of
      phosphorylated c-Jun (p-c-Jun) and phosphorylated c-Jun N-terminal kinase (p-JNK)
      are significantly associated with neuronal cell death in diabetic rat retinas and
      retinas exposed to high glucose. Retinas isolated from six adult male Sprague
      Dawley rats and six streptozotocin-induced diabetic rats (DM) were cultured in
      serum-free medium. The explants from non-diabetic controls were cultured in
      normal-glucose (N) or high-glucose (HG) medium. Furthermore, neurotrophin-4 (NT
      4) and Taurine-conjugated ursodeoxycholic acid (TUDCA) were incubated in HG
      medium. After 7 days, the numbers of regenerating neurites were counted per
      explant. After counting, the explants were fixed, cryosectioned, and stained by
      TUNEL, and also immunostained for p-c-Jun and p-JNK. The numbers of TUNEL
      positive, p-c-Jun- and p-JNK-immunopositive cells in the GCL were significantly
      higher and the numbers of regenerating neurites were significantly lower in the
      HG and the DM groups than in the N groups. In the HG groups supplemented with NT
      4 and TUDCA, the numbers of TUNEL-positive, p-c-Jun- and p-JNK-immunopositive
      cells were significantly lower and the numbers of neurites were significantly
      higher than in the HG group without NT-4 and TUDCA. Increased expression of p-c
      Jun and p-JNK is associated with neuronal cell death in diabetic rat retinas and
      retinas exposed to high glucose. Neuroprotective effect of TUDCA and NT-4 is
      correlated with the suppression of p-c-Jun and p-JNK expression. These results
      provide a better understanding of the neurodegenerative process underlying DR. 

PMID- 24333194
TI  - Cystic adventitial degeneration of the popliteal artery: report on 3 cases and
      review of the literature.
AB  - BACKGROUND: Cystic adventitial disease (CAD) is a rare, nonatherosclerotic
      vascular condition predominantly seen in middle-aged men with no cardiovascular
      risk factors. Three cases have been diagnosed and treated in our institution
      during the past 8 years. The purpose of this report is to provide an updated
      literature review of this condition with the addition of 3 new cases. METHODS:
      Information about 3 new cases is presented along with data obtained from articles
      published between 1979 and 2012 from PubMed and Embase databases. Two hundred
      thirty-eight articles were found, and 98 were included in our review. RESULTS:
      All patients treated presented with rapidly progressive intermittent calf
      claudication. Diagnosis of CAD was confirmed by at least 2 imaging techniques,
      either duplex ultrasound or magnetic resonance imaging, with a preoperative
      angiography performed in all cases. Wall cyst resection was performed in the 3
      cases reported here, after intraoperative confirmation that there was no arterial
      wall damage. All patients remained asymptomatic with no signs of recurrence after
      a median 36-month follow-up (24-60 month follow-up). CONCLUSIONS: CAD is a rare
      vascular condition usually affecting arteries that presents as a sudden onset of
      unilateral intermittent calf claudication. Diagnosis must be confirmed with
      imaging techniques, such as duplex ultrasonography and magnetic resonance
      imaging. On the basis of existing knowledge, surgery remains the treatment of
      choice, with cystic evacuation in cases with no arterial wall damage or resection
      and grafting. However, the follow-up algorithm for treated patients remains
      unclear.

PMID- 24333195
TI  - Ectopic drainage from the inferior vena cava to the left atrium together with a
      partial anomalous pulmonary venous connection.
AB  - We report a case of a 44-year-old male patient with ectopic drainage from the
      inferior vena cava to the left atrium accompanied by partial anomalous pulmonary
      venous drainage. After the patient was hospitalized, his diagnosis was confirmed
      by Doppler echocardiography and angiography. A pericardial patch was used to
      divert the blood to the atrium. The surgical procedure was successful, and the
      patient began a rehabilitation program 8 days later. This type of ectopic
      drainage pattern is an unusual and infrequent clinical finding. The definitive
      diagnosis should be made by Doppler ultrasound combined with angiography. 

PMID- 24333193
TI  - Immunosuppressive peptides and their therapeutic applications.
AB  - The immune system is vital for detecting and evading endogenous and exogenous
      threats to the body. Failure to regulate this homeostasis leads to autoimmunity,
      which is often associated with malfunctioning T cell signaling. Several
      medications are available to suppress over-reactive T lymphocytes, but many of
      the currently marketed drugs produce severe and life-threatening side-effects.
      Ribosomally synthesized peptides are gaining recognition from the pharmaceutical
      industry for their enhanced selectivity and decreased toxicity compared with
      small molecules; in particular, circular peptides exhibit remarkable stability
      and increased oral administration properties. For example, plant cyclotides
      effectively inhibit T lymphocyte proliferation. They are composed of a head-to
      tail cyclized backbone and a cystine-knot motif, which confers them with
      remarkable stability, thus making them attractive pharmaceutical tools. 

PMID- 24333192
TI  - The dendritic hypothesis for Alzheimer's disease pathophysiology.
AB  - Converging evidence indicates that processes occurring in and around neuronal
      dendrites are central to the pathogenesis of Alzheimer's disease. These data
      support the concept of a "dendritic hypothesis" of AD, closely related to the
      existing synaptic hypothesis. Here we detail dendritic neuropathology in the
      disease and examine how Abeta, tau, and AD genetic risk factors affect dendritic
      structure and function. Finally, we consider potential mechanisms by which these
      key drivers could affect dendritic integrity and disease progression. These
      dendritic mechanisms serve as a framework for therapeutic target identification
      and for efforts to develop disease-modifying therapeutics for Alzheimer's
      disease.

PMID- 24333196
TI  - Long-term outcomes of direct and indirect below-the-knee open revascularization
      based on the angiosome concept in diabetic patients with critical limb ischemia.
AB  - BACKGROUND: We compared long-term outcomes of isolated below-the-knee (BTK)
      bypass revascularization in diabetic patients presenting with critical limb
      ischemia (CLI) with and without achieving the bypass on the artery corresponding
      to the territory of the lesion based on the angiosome concept. MATERIALS: We
      analyzed outcomes of 58 consecutive CLI limbs of 54 diabetic patients presenting
      with tissue loss who underwent isolated BTK bypasses from 2003 to 2009 for crural
      occlusive arterial disease. Bypasses were classified into direct and indirect
      groups based on the angiosome concept, whether feeding artery flow to the site of
      ischemic tissue loss was achieved or not. We compared median ulcer-healing time,
      survival, primary patency, and limb salvage rates between both groups by Kaplan
      Meier analysis and log-rank test. Independent factors of major amputations were
      explored by univariate analysis. Variables with P < 0.2 in univariate analysis
      were submitted to multivariable analysis. RESULTS: Median ulcer-healing time was
      56 +/- 18 days in direct group (n = 36) and 112 +/- 45 days in indirect group (n
      = 22, P = 0.01). There was no difference between both groups in terms of survival
      or primary patency. Limb salvage rate was significantly higher in direct group
      than in indirect group: 91% vs. 66% at 1 year, 65% vs. 24% at 3 years, and 58%
      vs. 18% at 5 years, respectively (P = 0.03). After multivariable Cox proportional
      analysis, independent factors associated with major amputation were end-stage
      renal disease (P = 0.030) and C-reactive protein level (P = 0.025). CONCLUSIONS:
      Achieving a direct arterial flow based on angiosome concept in CLI diabetic
      patients presenting with tissue loss appears to be important for ulcer healing
      and limb salvage.

PMID- 24333197
TI  - Association between carotid artery occlusion and ultrasonographic plaque type.
AB  - BACKGROUND: Internal carotid artery (ICA) occlusion is associated with acute
      stroke and carries significant morbidity and mortality. The aim of this study was
      to examine whether ultrasonographic carotid plaque type may be associated with
      ICA occlusion. METHODS: Two hundred eleven patients (85% men, mean age 66.0+/-9.5
      years, 28.9% asymptomatic) with ICA occlusion were included in this case-control
      study. Ultrasonographic Gray-Weale plaque type (I-IV, echolucent to echogenic)
      characterization was obtained in both the occluded and the contralateral ICA.
      Univariate and conditional logistic regression analyses with 1:1 pair matching
      per artery were undertaken. Each contralateral carotid artery with stenosis was
      treated as control to the ipsilateral-occluded ICA of the same patient. RESULTS:
      A total of 261 ICAs (61.9%) were recorded with type I-II plaque, of which 165
      (63.2%) were among the occluded and 96 (36.8%) were among the contralateral ICAs
      with stenosis (P<0.001). Mean contralateral ICA stenosis was 58.2%+/-20.4%.
      Regression analysis showed that carotid plaque type I-II was significantly
      associated with carotid artery occlusion compared with plaque type III-IV (crude
      odds ratio [OR]=4.29, 95% confidence intervals [CI]=2.81-6.57%, P<0.001, adjusted
      OR=5.60, 95% CI=3.23-9.70, P<0.001). Previous neurological events did not seem to
      be significantly associated with plaque echolucency (OR=0.62, 95% CI=0.29-1.35,
      P=0.23). CONCLUSIONS: A significant association between echolucent plaque and ICA
      occlusion was observed. This observational hypothesis may prompt for further
      investigation of the causal mechanism between carotid plaque type and ICA
      occlusion by larger cohort studies.

PMID- 24333198
TI  - Nonaneurysmal infectious aortitis.
AB  - Infectious aortitis is a rare disease in the antibiotic era. Only a small number
      of cases of nonaneurysmal infectious aortitis are discussed in literature, and
      its true incidence and natural history are not well defined. We present here a
      case of typical nonaneurysmal infectious aortitis with literature review of 19
      cases of aortic infection in which the aorta is initially normal in caliber. 

PMID- 24333199
TI  - Pulmonary embolectomy in elderly patients.
AB  - OBJECTIVE: The relation of age to case fatality rate in patients undergoing
      pulmonary embolectomy has not been reported. In view of the importance of age in
      the selection of patients who may be candidates for pulmonary embolectomy, we
      explored the database of the Nationwide Inpatient Sample to determine the impact
      of age on the case fatality rate. METHODS: Patients with pulmonary embolism who
      underwent pulmonary embolectomy in short-stay hospitals throughout the United
      States, 1999-2008, were identified from the Nationwide Inpatient Sample. In
      hospital all-cause case fatality rate was assessed according to age. RESULTS: The
      proportion of patients who underwent pulmonary embolectomy decreased with age
      among both stable and unstable patients. Case fatality rate with pulmonary
      embolectomy in stable patients increased with age beginning at age 51 to 60
      years. Among patients aged 51 to 60 years, the case fatality rate was 100 of 575
      (17.4%). This rate increased to 60 of 130 (46.2%) among patients aged more than
      80 years (P < .0001). The case fatality rate did not correlate with age in
      unstable patients. CONCLUSIONS: The case fatality rate with pulmonary embolectomy
      in stable patients increases with age greater than 51 to 60 years and is high
      among the elderly. The case fatality rate with pulmonary embolectomy in unstable
      patients does not seem to be related to age.

PMID- 24333200
TI  - Perioperative management of patients with Parkinson's disease.
AB  - Parkinson's disease is the second most common neurodegenerative disease
      worldwide, leading to a wide range of disability and medical complications.
      Managing patients with Parkinson's disease in the perioperative hospital setting
      can be particularly challenging. Suboptimal management can lead to medical
      complications, prolonged hospital stays, and delayed recovery. This review aims
      to address the most important issues related to caring for patients with
      Parkinson's disease perioperatively who are undergoing emergent or planned
      general surgery. It also intends to help hospitalists, internists, and other
      health care providers mitigate potential in-hospital morbidity and prevent
      prolonged recovery. Challenges in managing patients with Parkinson's disease in
      the perioperative hospital setting include disruption of medication schedules,
      "nothing by mouth" status, reduced mobility, and medication interactions and
      their side effects. Patients with Parkinson's disease are more prone to
      immobility and developing dysphagia, respiratory dysfunction, urinary retention,
      and psychiatric symptoms. These issues lead to higher rates of pneumonia, urinary
      tract infections, deconditioning, and falls compared with patients without
      Parkinson's disease, as well as prolonged hospital stays and a greater need for
      post-hospitalization rehabilitation. Steps can be taken to decrease these
      complications, including minimizing nothing by mouth status duration, using
      alternative routes of drugs administration when unable to give medications
      orally, avoiding drug interactions and medications that can worsen parkinsonism,
      assessing swallowing ability frequently, encouraging incentive spirometry,
      performing bladder scans, avoiding Foley catheters, and providing aggressive
      physical therapy. Knowing and anticipating these potential complications allow
      hospital physicians to mitigate nosocomial morbidity and shorten recovery times
      and hospital stays. 

PMID- 24333201
TI  - The clinical encounter revisited.
AB  - The patient-physician encounter is the pivotal starting point of any healthcare
      delivery, but it is subject to multiple process breakdowns and prevalent
      suboptimal performance. An overview of the techniques and components of a
      successful encounter valid for every setting and readily applicable is presented,
      stressing 7 rules: (1) ensuring optimal environment, tools, and teamwork; (2)
      viewing each encounter not only as a cognitive/biomedical challenge, but also as
      a personal one, and a learning opportunity; (3) adopting an attitude of
      curiosity, concentration, compassion, and commitment, and maintaining a
      systematic, orderly approach; (4) "simple is beautiful"-making the most of the
      basic clinical data and their many unique advantages; (5) minding "the silent
      dimension"-being attentive to the patient's identity and emotions; (6) following
      the "Holy Trinity" of gathering all information, consulting databases/colleagues,
      and tailoring gained knowledge to the individual patient; and (7) using the
      encounter as a "window of opportunity" to further the patient's health-not just
      the major problem, by addressing screening and prevention; promoting health
      literacy and shared decision-making; and establishing proper follow-up. Barriers
      to implementation identified can be overcome by continuous educational
      interventions. A high-quality encounter sets a virtuous cycle of patient-provider
      interaction and results in increasing satisfaction, adherence, and improved
      health outcomes.

PMID- 24333202
TI  - Dental surgery and antiplatelet agents: bleed or die.
AB  - In patients taking antiplatelet medications who are undergoing dental surgery,
      physicians and dentists must weigh the bleeding risks in continuing antiplatelet
      medications versus the thrombotic risks in interrupting antiplatelet medications.
      Bleeding complications requiring more than local measures for hemostasis are rare
      after dental surgery in patients taking antiplatelet medications. Conversely, the
      risk for thrombotic complications after interruption of antiplatelet therapy for
      dental procedures apparently is significant, although small. When a clinician is
      faced with a decision to continue or interrupt antiplatelet therapy for a dental
      surgical patient, the decision comes down to "bleed or die." That is, there is a
      remote chance that continuing antiplatelet therapy will result in a (nonfatal)
      bleeding problem requiring more than local measures for hemostasis versus a small
      but significant chance that interrupting antiplatelet therapy will result in a
      (possibly fatal) thromboembolic complication. The decision is simple: It is time
      to stop interrupting antiplatelet therapy for dental surgery. 

PMID- 24333203
TI  - Levothyroxine dosage is associated with stability of thyroid-stimulating hormone
      values.
AB  - OBJECTIVE: In patients treated for hypothyroidism, the usual practice is to
      monitor thyroid-stimulating hormone values yearly once a therapeutic dosage of
      levothyroxine is determined. This study investigates whether there are any
      clinical predictors that could identify a subset of patients who might be
      monitored safely on a less frequent basis. METHODS: With the use of a
      retrospective study design, 715 patients treated for hypothyroidism who had a
      normal (ie, therapeutic) thyroid-stimulating hormone value in 2006 while taking
      levothyroxine were identified. All thyroid-stimulating hormone values were then
      obtained through December 31, 2012. By using a Cox proportional hazard model,
      gender, age, body mass index, history of chronic autoimmune thyroiditis, initial
      thyroid-stimulating hormone level, and levothyroxine dose were analyzed for time
      to first abnormal thyroid-stimulating hormone value. RESULTS: Age, gender,
      history of chronic autoimmune thyroiditis, and body mass index at the time of
      initial normal thyroid-stimulating hormone were not associated significantly with
      time to abnormal thyroid-stimulating hormone value. Levothyroxine dose >125
      MUg/day had an increased hazard ratio of 2.4 (95% confidence interval, 1.7-3.4; P
      < .0001) for time to first follow-up abnormal thyroid-stimulating hormone value,
      but dosages less than that did not increase the hazard ratio. One year after the
      initial normal thyroid-stimulating hormone value, 91.1% of patients taking <= 125
      MUg/day had a continued normal thyroid-stimulating hormone, whereas only 73.3% of
      patients taking >125 MUg/day did. Transformed thyroid-stimulating hormone value
      (which represents a measure of how far the initial thyroid-stimulating hormone
      was from the midpoint of the normal range) also had an increased hazard ratio of
      1.14 (95% confidence interval, 1.1-1.2; P < .0001) for time to first abnormal
      thyroid-stimulating hormone value. CONCLUSIONS: For patients receiving <= 125
      MUg/day of levothyroxine, we propose that a testing interval up to 2 years may be
      acceptable if their thyroid-stimulating hormone is well within the normal range.

PMID- 24333204
TI  - Electronic health record use, intensity of hospital care, and patient outcomes.
AB  - OBJECTIVE: Previous studies have suggested that weekend hospital care is inferior
      to weekday care and that this difference may be related to diminished care
      intensity. The purpose of this study was to determine whether a metric for
      measuring intensity of hospital care based on use of the electronic health record
      was associated with patient-level outcomes. METHODS: We performed a cohort study
      of hospitalizations at an academic medical center. Intensity of care was defined
      as the hourly number of provider accessions of the electronic health record,
      termed "electronic health record interactions." Hospitalizations were categorized
      on the basis of the mean difference in electronic health record interactions
      between the first Friday and the first Saturday of hospitalization. We used
      regression models to determine the association of these categories with patient
      outcomes after adjusting for covariates. RESULTS: Electronic health record
      interactions decreased from Friday to Saturday in 77% of the 9051
      hospitalizations included in the study. Compared with hospitalizations with no
      change in Friday to Saturday electronic health record interactions, the relative
      lengths of stay for hospitalizations with a small, moderate, and large decrease
      in electronic health record interactions were 1.05 (95% confidence interval [CI],
      1.00-1.10), 1.11 (95% CI, 1.05-1.17), and 1.25 (95% CI, 1.15-1.35), respectively.
      Although a large decrease in electronic health record interactions was associated
      with in-hospital mortality, these findings were not significant after risk
      adjustment (odds ratio 1.74, 95% CI, 0.93-3.25). CONCLUSIONS: Intensity of
      inpatient care, measured by electronic health record interactions, significantly
      diminished from Friday to Saturday, and this decrease was associated with length
      of stay. Hospitals should consider monitoring and correcting temporal
      fluctuations in care intensity.

PMID- 24333205
TI  - A historical and practical review of first trimester aneuploidy screening.
AB  - There have been tremendous advancements over the past three decades in prenatal
      screening for aneuploidy and we have changed our practice from screening by
      maternal age alone to 'combined' first trimester screening and circulating cell
      free fetal DNA. We currently use the nuchal translucency and biochemical markers
      of free beta-hCG and PAPP-A to determine the risk of fetal aneuploidy. The
      primary goal is to identify higher risk women for fetal aneuploidy early in
      pregnancy and give them the option to pursue invasive testing in a timely manner
      if desired. 

PMID- 24333206
TI  - Urgent global opportunities to prevent birth defects.
AB  - Birth defects are an urgent global health priority. They affect millions of
      births worldwide. But their prevalence and impact are largely under-ascertained,
      particularly in middle- and low-income countries. Fortunately, a large proportion
      of birth defects can be prevented. This review examines the global prevalence and
      primary prevention methods for major preventable birth defects: congenital
      rubella syndrome, folic acid-preventable spina bifida and anencephaly, fetal
      alcohol syndrome, Down syndrome, rhesus hemolytic disease of the fetus and the
      newborn; and those associated with maternal diabetes, and maternal exposure to
      valproic acid or iodine deficiency during pregnancy. Challenges to prevention
      efforts are reviewed. The aim of this review is to bring to the forefront the
      urgency of birth defects prevention, surveillance, and prenatal screening and
      counseling; and to help public health practitioners develop population-based
      birth defects surveillance and prevention programs, and policy-makers to develop
      and implement science-based public health policies. 

PMID- 24333207
TI  - In silico predicted structural and functional robustness of piscine
      steroidogenesis.
AB  - Assessments of metabolic robustness or susceptibility are inherently dependent on
      quantitative descriptions of network structure and associated function. In this
      paper a stoichiometric model of piscine steroidogenesis was constructed and
      constrained with productions of selected steroid hormones. Structural and flux
      metrics of this in silico model were quantified by calculating extreme pathways
      and optimal flux distributions (using linear programming). Extreme pathway
      analysis showed progestin and corticosteroid synthesis reactions to be highly
      participant in extreme pathways. Furthermore, reaction participation in extreme
      pathways also fitted a power law distribution (degree exponent gamma=2.3), which
      suggested that progestin and corticosteroid reactions act as 'hubs' capable of
      generating other functionally relevant pathways required to maintain steady-state
      functionality of the network. Analysis of cofactor usage (O2 and NADPH) showed
      progestin synthesis reactions to exhibit high robustness, whereas estrogen
      productions showed highest energetic demands with low associated robustness to
      maintain such demands. Linear programming calculated optimal flux distributions
      showed high heterogeneity of flux values with a near-random power law
      distribution (degree exponent gamma>=2.7). Subsequently, network robustness was
      tested by assessing maintenance of metabolite flux-sum subject to targeted
      deletions of rank-ordered (low to high metric) extreme pathway participant and
      optimal flux reactions. Network robustness was susceptible to deletions of
      extreme pathway participant reactions, whereas minimal impact of high flux
      reaction deletion was observed. This analysis shows that the steroid network is
      susceptible to perturbation of structurally relevant (extreme pathway) reactions
      rather than those carrying high flux. 

PMID- 24333208
TI  - A novel method to study aging in bacteria that reproduce by morphologically
      symmetric fission.
AB  - The study of aging in fission bacteria has been especially difficult because of
      the challenge in identifying older sibling cells due to their morphological
      similarity to younger sibling cells. This study develops a generic method solely
      based on the analysis of cell growth rate (rate of cell volume increase). The
      proposed method does not require any special assumptions or measurements
      regarding the physical features of older siblings, such as older cell poles or
      slightly greater cell sizes. Therefore, the proposed method is applicable to the
      study of far more types of bacteria than those of existing methods. Bacteria that
      can be examined using this method include, but are not limited to, the following
      categories: (1) cocci bacteria in which tracking a larger number of old pole
      cells through successive generations is formidable, (2) possible bacteria where
      cell poles are either weakly correlated or uncorrelated to aging, and (3)
      bacteria that reproduce by multiple-fission. This new method provides a useful
      tool to study the relationship between cell poles and aging in bacteria. 

PMID- 24333209
TI  - The mechanical cost of transport of fast running animals.
AB  - Regarding running animals, algebraic expressions for the horizontal (omegax) and
      vertical (omegay) components of the mechanical cost of transport are deduced for
      a ground force pattern based on the Spring-mass model. Defining MU~ as the
      maximum ground forces ratio MU~=max(Fx)/max(Fy), the analysis shows that the
      mechanical cost of transport omegax+omegay for fast running animals is
      approximately proportional to MU~, and to the relative contact length, and
      positively correlated to the limb take-off angle and the collision angle. The
      vertical cost omegay is shown to approximate to zero for fast running animals.
      Sustained top running speeds are predicted to require the largest possible values
      of MU~ and therefore relatively large horizontal propulsive forces, as well as a
      minimum possible ground contact time. The equations also show that animals
      running relatively slow would tend to prefer certain interval of values for
      parameter MU~, which would minimize both their mechanical cost of transport and
      their metabolic cost of transport. Very large animals are suspected to be less
      capable of developing large values of MU~, which possibly renders them incapable
      of developing great speeds. 

PMID- 24333210
TI  - Neural correlates of ideomotor effect anticipations.
AB  - How does our mind produce physical, goal-directed action of our body? For about
      200years, philosophers and psychologists hypothesized the transformation from
      mind to body to rely on the anticipation of an action's sensory consequences.
      Whereas this hypothesis received tremendous support from behavioral experiments,
      the neural underpinnings of action control via such ideomotor effect
      anticipations are virtually unknown. Using functional magnetic resonance imaging,
      the present study identified the inferior parietal cortex and the parahippocampal
      gyrus as key regions for this type of action control - setting the stage for a
      neuroscientific framework for explaining action control by ideomotor effect
      anticipations and thus enabling a synthesis of psychological and neuroscientific
      approaches to human action. 

PMID- 24333212
TI  - Ascorbic acid supplementation enhances recovery from ethanol induced inhibition
      of Leydig cell steroidogenesis than abstention in male guinea pigs.
AB  - The impact of ascorbic acid supplementation against ethanol induced Leydig cell
      toxicity was studied in guinea pigs. Male guinea pigs were exposed to ethanol
      (4g/kgb.wt.) for 90 days. After 90 days, ethanol administration was completely
      stopped and animals in the ethanol group were divided into abstention group and
      ascorbic acid supplemented group (25mg/100gb.wt.) and those in control group were
      maintained as control and control+ascorbic acid group. Ethanol administration
      reduced the serum testosterone and LH (luteinising hormone) levels and elevated
      estradiol levels. Cholesterol levels in Leydig cell were increased whereas the
      mRNA and protein expressions of StAR (steroidogenic acute regulatory) protein,
      cytochrome P450scc (cytochrome p450side chain cleavage enzyme), 3beta-HSD (3beta
      hydroxysteroid dehydrogenase), 17beta-HSD (17beta-hydroxysteroid dehydrogenase)
      and LH receptor were drastically reduced. Administration of ascorbic acid
      resulted in alteration of all these parameters indicating enhanced recovery from
      ethanol induced inhibition of Leydig cell steroidogenesis. Although abstention
      could also reduce the inhibition of steroidogenesis, this was lesser in
      comparison with ascorbic acid supplemented group. 

PMID- 24333211
TI  - A group of non-serotonergic cells is CO2-stimulated in the medullary raphe.
AB  - Serotonin/substance P synthesizing cells in the raphe nuclei of the brain are
      candidates for designation as central chemoreceptors that are stimulated by
      CO2/pH. We have previously demonstrated that these neurons are CO2-stimulated in
      situ. Evidence also suggests that CO2-inhibited raphe neurons recorded in vitro
      and in situ synthesize GABA. Unknown is whether there are other types of
      chemosensitive cells in the raphe. Here, we showed that a previously unrecognized
      pool of raphe neurons also exhibit chemosensitivity, and that they are not
      serotonergic. We used extracellular recording of individual raphe neurons in the
      unanesthetized juvenile rat in situ perfused decerebrate brainstem preparation to
      assess chemosensitivity of raphe neurons. Subsequent juxtacellular labeling of
      individually recorded cells, and immunohistochemistry for the serotonin
      synthesizing enzyme tryptophan hydroxylase and for neurokinin-1 receptor (NK1R;
      the receptor for substance P) indicated a group of CO2-stimulated cells that are
      not serotonergic, but express NK1R and are closely apposed to surrounding
      serotonergic cells. CO2-stimulated 5-HT and non-5-HT cells constitute distinct
      groups that have different firing characteristics and hypercapnic sensitivities.
      Non-5-HT cells fire faster and are more robustly stimulated by CO2 than are 5-HT
      cells. Thus, we have characterized a previously unrecognized type of CO2
      stimulated medullary raphe neuron that is not serotonergic, but may receive input
      from neighboring serotonin/substance P synthesizing chemosensitive neurons. The
      potential network properties of the three types of chemosensitive raphe neurons
      (the present non-5-HT cells, serotonergic cells, and CO2-inhibited cells) remain
      to be elucidated. 

PMID- 24333213
TI  - Cucurbitacin B inhibits the translational expression of hypoxia-inducible factor
      1alpha.
AB  - Cucurbitacin B is a triterpenoid compound isolated from Trichosanthes kirilowii
      Maximowicz, which has been used in oriental medicine for its antitumor
      activities. However, the mechanisms by which cucurbitacin B inhibits tumor growth
      are not fully understood. We here demonstrated the effect of cucurbitacin B on
      hypoxia-inducible factor-1 (HIF-1) activation. Cucurbitacin B showed the potent
      inhibitory activity against HIF-1 activation induced by hypoxia in various human
      cancer cell lines. This compound markedly decreased the hypoxia-induced
      accumulation of HIF-1alpha protein dose-dependently, whereas it did not affect
      the expressions of HIF-1beta. Further analysis revealed that cucurbitacin B
      inhibited HIF-1alpha protein synthesis, without affecting the expression level of
      HIF-1alpha mRNA or degradation of HIF-1alpha protein. Rather, we found that
      suppression of HIF-1alpha accumulation by cucurbitacin B correlated with strong
      dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors
      ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding
      protein-1 (4E-BP1) and extracellular signal-regulated kinase-1/2 (ERK1/2), a
      pathway known to regulate HIF-1alpha expression at the translational level.
      Cucurbitacin B also activated Akt, a mechanistic feature exhibited by established
      mTOR inhibitors in many tumor cells. Furthermore, cucurbitacin B prevented
      hypoxia-induced expression of HIF-1 target genes and suppresses the invasiveness
      of tumor cells. In vivo studies further confirmed the inhibitory effect of
      cucurbitacin B on the expression of HIF-1alpha proteins, leading to a decrease
      growth of HeLa cells in a xenograft tumor model. These results show that
      cucurbitacin B is an effective inhibitor of HIF-1 and provide new perspectives
      into the mechanism of its anticancer activity. 

PMID- 24333214
TI  - SP600125 overcomes antimitotic drug-resistance in cancer cells by increasing
      apoptosis with independence of P-gp inhibition.
AB  - The purpose of this study was to identify conditions that increase the
      sensitivity of resistant cancer cells to antimitotic drugs. Using MTS assays,
      microscopic observation, assessment of cleaved PARP, FACS analysis, and Hoechst
      staining, we found that the c-Jun N-terminal kinase (Jnk) inhibitor SP600125 (SP)
      sensitized the antimitotic drug-resistant KBV20C cancer cell line. The
      sensitization mechanism was independent of p-glycoprotein (P-gp) inhibition.
      Interestingly, SP-induced sensitization was greater in resistant KBV20C cancer
      cells than in KB parent cells. The mechanism of SP-induced sensitization involved
      G2 arrest. KBV20C cells treated with SP and antimitotic drugs were more
      sensitized than cells treated with SP alone. This suggests that SP can restore
      sensitization for antimitotic drugs in resistant cancer cells. Our findings may
      contribute to the development of SP-based combination therapies for patients
      receiving anti-cancer agents that target microtubules. 

PMID- 24333215
TI  - Mepivacaine-induced contraction involves increased calcium sensitization mediated
      via Rho kinase and protein kinase C in endothelium-denuded rat aorta.
AB  - Mepivacaine is an aminoamide local anesthetic that produces vasoconstriction in
      vivo and in vitro. The goals of this in vitro study were to determine whether
      mepivacaine-induced contraction involves calcium sensitization in isolated
      endothelium-denuded aortas, and to investigate the specific protein kinases
      involved. The effects of mepivacaine and potassium chloride on intracellular
      calcium concentrations ([Ca(2+)]i) and tension in the presence or absence of Y
      27632 or GF 109203X were measured simultaneously using the acetoxymethyl ester of
      fura-2-loaded aortic strips. Cumulative mepivacaine concentration-response curves
      were generated in the presence or absence of the following inhibitors: Rho kinase
      inhibitor Y-27632, protein kinase C (PKC) inhibitor GF 109203X, extracellular
      signal-regulated kinase (ERK) inhibitor PD 98059, c-Jun NH2-terminal kinase (JNK)
      inhibitor SP600125, and p38 mitogen-activated protein kinase (MAPK) inhibitor SB
      203580. Phosphorylation of PKC and MAPK, and membrane translocation of Rho kinase
      were detected in vascular smooth muscle cells by Western blotting. The slope of
      the mepivacaine-induced [Ca(2+)]i-tension curve was higher than that of the KCl
      induced [Ca(2+)]i-tension curve. Pretreatment with Y-27632 or GF 109203X shifted
      the mepivacaine-induced [Ca(2+)]i-tension curve to the lower right. Pretreatment
      with Y-27632, GF 109203X, PD 98059, or SP600125 attenuated mepivacaine-induced
      contraction in a concentration-dependent manner. Y-27632 and GF 109203X
      attenuated mepivacaine-induced Rho kinase membrane translocation and PKC
      phosphorylation, respectively. PD 98059 and SP600125 attenuated mepivacaine
      induced ERK and JNK phosphorylation, respectively. Taken together, these results
      indicate that mepivacaine-induced contraction involves increased calcium
      sensitization mediated by Rho kinase and PKC. Such contraction mainly involves
      activation of ERK- and JNK-mediated pathways. 

PMID- 24333216
TI  - Extracellular calcium modulates the inhibitory effect of 4-aminopyridine on Kv
      current in vascular smooth muscle cells.
AB  - 4-Aminopyridine is widely used as a Kv channel blocker. However, its mechanism of
      action is still a matter of debate. Extracellular calcium as well as 4
      aminopyridine have been reported to interact with the activation kinetics of
      particular Kv channels. The objective of the present study was to investigate
      whether extracellular calcium could modulate the inhibition of Kv current by 4
      aminopyridine in vascular myocytes. Kv current was recorded by using whole-cell
      patch-clamp in freshly isolated smooth muscle cells from rat mesenteric artery.
      Macroscopic properties of Kv current were not affected by change in extracellular
      calcium from 0 to 2mM. During a 10s depolarizing pulse, 4-aminopyridine inhibited
      the peak current without affecting the end-pulse current. The concentration
      effect curve of 4-aminopyridine was shifted to the left in the presence of 2mM
      calcium compared to 0 calcium. After 4-aminopyridine washout, current recovery
      from block was slower in the presence than in the absence of calcium. Inhibition
      of Kv current by 4-aminopyridine (0.5mM) and the Kv2 blocker stromatoxin (50nM)
      was additive and stromatoxin did not alter the potentiation of 4-aminopyridine
      effect by extracellular calcium. These results showed that extracellular calcium
      modulated the inhibitory potency of 4-aminopyridine on Kv current in vascular
      myocytes. The component of Kv current that was inhibited by 4-aminopyridine in a
      calcium-sensitive manner was distinct from Kv2 current. 

PMID- 24333217
TI  - Combination of carvacrol with methotrexate suppresses Complete Freund's Adjuvant
      induced synovial inflammation with reduced hepatotoxicity in rats.
AB  - The present study evaluated the therapeutic benefit of the combination of
      carvacrol, an isoprenoid having potential anti-inflammatory action, with
      methotrexate in suppressing Complete Freund's Adjuvant induced arthritis and
      attenuating methotrexate induced hepatic damage. Arthritis was induced in rats
      with Complete Freund's Adjuvant. Animals received methotrexate (2mg/kg)
      intraperitonealy once a week for 5 weeks alone and along with carvacrol orally
      (50 and 100mg/kg) respectively from the 10th to the 42nd day. Control and
      carvacrol alone group were also studied. Paw volume, hypernociception, and
      erythrocyte sedimentation rate were evaluated as arthritic markers. Hepatic
      marker enzymes in serum; myeloperoxidase, protein oxidation, and oxidative
      measures were determined in the liver homogenate. Liver histological assessments
      were also carried out. Methotrexate significantly controlled arthritis; however,
      liver damage was evident due to oxidative stress and rise in myeloperoxidase
      levels. Carvacrol suppressed the hyperalgesic response, significantly alleviated
      arthritis and reduced damage to the hepatocytes owing to a decline in the levels
      of myeloperoxidase and oxidative markers. High dose of the combination reduced
      the levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase
      and alkaline phosphatase by 24.74%, 30.2% and 28.14% compared with methotrexate
      treatment. Histological assessment also revealed that carvacrol minimizes
      methotrexate induced liver toxicity. In combination, carvacrol promoted the anti
      arthritic action of methotrexate, reduced neutrophils infiltration and
      peroxidative damage to the liver. Therefore, carvacrol can serve as a useful
      adjuvant and promote the safe use of methotrexate in the management of arthritis.

PMID- 24333218
TI  - Acquisition of epithelial-mesenchymal transition phenotype and cancer stem cell
      like properties in cisplatin-resistant lung cancer cells through AKT/beta
      catenin/Snail signaling pathway.
AB  - Cisplatin is a first-line chemotherapeutic agent in the treatment of non-small
      cell lung cancer (NSCLC), but the therapeutic effect is disappointing, partly due
      to drug resistance. Emerging evidence showed that chemoresistance associates with
      acquisition of epithelial-mesenchymal transition (EMT) phenotype and cancer stem
      cell-like properties. However, the underlying mechanism is not entirely clear. In
      this study, we showed that cisplatin-resistant A549 cells (A549/CDDP) acquire EMT
      phenotype associated with migratory and invasive capability. A549/CDDP cells also
      displayed enhanced cancer stem cell-like properties. Increased expression of
      transcription factor Snail, but not ZEB1, Slug and Twist, was observed in
      A549/CDDP cells. Knockdown of Snail reversed EMT and significantly attenuated
      migration, invasion and cancer stem cell-like properties of A549/CDDP cells.
      Conversely, overexpressed Snail in A549 cells induced EMT and cancer stem cell
      like properties. Finally, we demonstrated that activated AKT signal leads to
      increased beta-catenin expression and subsequently up-regulates Snail in
      A549/CDDP cells. Taken together, these results revealed that AKT/beta
      catenin/Snail signaling pathway is mechanistically associated with cancer stem
      cell-like properties and EMT features of A549/CDDP cells, and thus, this pathway
      could be a novel target for the treatment of NSCLC. 

PMID- 24333219
TI  - Mildronate, the inhibitor of L-carnitine transport, induces brain mitochondrial
      uncoupling and protects against anoxia-reoxygenation.
AB  - The preservation of mitochondrial function is essential for normal brain function
      after ischaemia-reperfusion injury. l-carnitine is a cofactor involved in the
      regulation of cellular energy metabolism. Recently, it has been shown that
      mildronate, an inhibitor of l-carnitine transport, improves neurological outcome
      after ischaemic damage of brain tissues. The aim of the present study was to
      elucidate the mitochondria targeted neuroprotective action of mildronate in the
      model of anoxia-reoxygenation-induced injury. Wistar rats were treated daily with
      mildronate (per os; 100mg/kg) for 14 days. The acyl-carnitine profile was
      determined in the brain tissues. Mitochondrial respiration and the activities of
      carnitine acetyltransferase (CrAT) and tricarboxylic acid (TCA) cycle enzymes
      were measured. To assess tolerance to ischaemia, isolated mitochondria were
      subjected to anoxia followed by reoxygenation. The mildronate treatment
      significantly reduced the concentrations of free l-carnitine (FC) and short-chain
      acyl-carnitine (AC) in brain tissue by 40-76%, without affecting the AC:FC ratio.
      The activities of CrAT and TCA cycle enzymes were slightly increased after
      mildronate treatment. Despite partially induced uncoupling, mildronate treatment
      did not affect mitochondrial bioenergetics function under normoxic conditions.
      After exposure to anoxia-reoxygenation, state 3 respiration and the respiration
      control ratio were higher in the mildronate-treated group. The results obtained
      demonstrate that mildronate treatment improves tolerance against anoxia
      reoxygenation due to an uncoupling preconditioning-like effect. Regulating l
      carnitine availability provides a potential novel target for the treatment of
      cerebral ischaemia and related complications. 

PMID- 24333220
TI  - Age- and time-dependent model of the prevalence of non-communicable diseases and
      application to dementia in Germany.
AB  - We derive a partial differential equation (PDE) that models the age-specific
      prevalence of a disease as a function of the incidence, remission and mortality
      rates. The main focus is on non-communicable diseases (NCDs), although the PDE is
      not restricted to NCDs. As an application of the PDE, the number of persons with
      dementia in Germany until the year 2050 is estimated based on German incidence
      data and official population projections. Uncertainty is treated by different
      scenarios about life expectancy, number of migrants, prevalence of the disease in
      migrants, and scenarios about the future incidence, and mortality of demented
      persons. Life expectancy and incidence of dementia have the strongest impact on
      the future number of persons with dementia. In nearly all scenarios, our
      estimated case numbers exceed former estimates. Furthermore, we use an example to
      show that the PDE method yields more accurate results than a common alternative
      approach. 

PMID- 24333221
TI  - Sleep problems and mortality in rural South Africa: novel evidence from a low
      resource setting.
AB  - OBJECTIVE: Sleep problems are associated with mortality in Western populations.
      In low-resource settings, evidence of sleep problems and their potential
      association with mortality is lacking. Our study aimed to fill this gap by
      examining the prospective association of sleep problems with mortality among
      older adults in rural South Africa, as well as potential sex differences in this
      association. METHODS: The study was conducted in 2006 in Agincourt (South
      Africa), as part of the Health and Demographic Surveillance System. A community
      wide sample of 4044 men and women aged 50 years or older participated in the
      survey. Two measures of sleep quality over the last 30 days were assessed
      alongside sociodemographic variables, measures of quality of life (QoL), and
      functional ability. Cox proportional hazard models were used to estimate hazard
      ratios (HR) and 95% confidence intervals (CI) for mortality risk over time
      associated with the two sleep measures at baseline, while allowing adjustment for
      other covariates. RESULTS: Overall, 394 deaths occurred during 3 years of follow
      up. Both men and women reporting severe/extreme nocturnal sleep problems (vs
      none/mild/moderate) experienced a significantly greater mortality risk in models
      adjusted for sociodemographic variables only (HR, 1.65 [95% CI, 1.18-2.31] and
      HR, 1.42 [95% CI, 1.07-1.88], respectively). However, these associations were
      nonsignificant in fully adjusted models (HR, 1.23 [95% CI, 0.85-1.79] and HR,
      1.07 [95% CI, 0.78-1.47], respectively). Men who reported severe/extreme
      difficulty related to daytime function (vs none/mild/moderate) experienced a 2
      fold increased mortality risk (HR, 2.01 [95% CI, 1.32-3.07]) in fully adjusted
      models, whereas no significant association was observed for women (1.16 [95% CI,
      0.80-1.67]). CONCLUSIONS: In this population, nocturnal sleep problems were not
      associated with mortality once analyses were adjusted for QoL, functional
      ability, and psychologic comorbidities. By contrast, severe or extreme problems
      with feeling unrested or unrefreshed during the day were associated with a 2-fold
      increased mortality risk, but this association was only significant in men.

PMID- 24333224
TI  - Trying to fall asleep while catastrophising: what sleep-disordered adolescents
      think and feel.
AB  - OBJECTIVE: Catastrophising is a repetitive cognitive process related to sleep
      disturbance in adult insomnia patients. More recently catastrophising has been
      associated with increased sleep disturbances in community samples of children and
      adolescents, with this association mediated by anxiety and depression. However,
      there currently is no evidence of these processes outside of community samples;
      impeding our ability to draw clinical conclusions. Knowledge on such
      dysfunctional cognitive processes in adolescents experiencing sleep disturbance
      would be clinically beneficial in aetiology and intervention. Our research
      examined the link between catastrophising, anxiety, depression and sleep latency
      in a sample of sleep-disordered adolescents. We also explored specific
      catastrophising themes which may impact the sleep latency of these adolescents.
      METHOD: Forty adolescents (age=15.1+/-1.5 years, 53% boys) diagnosed with delayed
      sleep phase disorder completed a 7-day sleep diary, along with measures of
      anxiety and depression and a catastrophising interview with a trained sleep
      therapist. RESULTS: Several catastrophisation themes were generated, the most
      common concerning interpersonal and performance aspects of school. Bootstrapping
      analyses showed depression did not mediate the relationship between
      catastrophising and sleep; however, an indirect relationship was found between
      catastrophising, anticipatory anxiety, and sleep latency. CONCLUSION: These
      findings have implications for the role of dysfunctional thinking in prolonging
      sleep onset for adolescents and providing a clinical framework for health
      professionals when assessing and treating adolescents with delayed sleep timing.

PMID- 24333223
TI  - Prevalence of insomnia symptoms in a general population sample of young children
      and preadolescents: gender effects.
AB  - OBJECTIVE: Our population-based study examined the prevalence of insomnia
      symptoms and its sociodemographic, subjective, and polysomnographic (PSG) sleep
      risk factors in young and preadolescent children. METHODS: We performed a cross
      sectional study of 700 children, ages 5-12 years who underwent a 9-h PSG and
      parent-completed sleep and development questionnaires (Penn State Child Cohort).
      Insomnia symptoms were defined as parent report of difficulty falling or staying
      asleep and sleep-disordered breathing (SDB) as an apnea hypopnea index of >=1.
      RESULTS: The prevalence of insomnia symptoms was 19.3% and did not significantly
      change (20.2%) when children with SDB were excluded. A significant interaction
      between gender and age revealed that the prevalence of insomnia symptoms was
      highest in girls ages 11 to 12 years (30.6%). This gender difference was not
      associated with significant differences between girls and boys ages 11-12 years
      in anxiety and depressive symptoms. In contrast girls ages 11-12 years with
      insomnia symptoms, but not boys of the same group, demonstrated clinically
      significant PSG sleep disturbances compared to those without insomnia symptoms.
      CONCLUSIONS: These data suggest that one out of five young children and
      preadolescents of the general population have insomnia symptoms. Importantly, the
      prevalence of insomnia symptoms peaks in girls ages 11 to 12 years and is
      associated with objective sleep disturbances which may be related to hormonal
      changes associated with the onset of puberty rather than anxiety and depression.

PMID- 24333222
TI  - Habitual sleep duration associated with self-reported and objectively determined
      cardiometabolic risk factors.
AB  - BACKGROUND: Self-reported short or long sleep duration has been associated with
      adverse cardiometabolic health outcomes in laboratory and epidemiologic studies,
      but interpretation of such data has been limited by methodologic issues. METHODS:
      Adult respondents of the 2007-2008 US National Health and Nutrition Examination
      Survey (NHANES) were examined in a cross-sectional analysis (N=5649). Self
      reported sleep duration was categorized as very short (<5 h), short (5-6 h),
      normal (7-8 h), or long (>=9 h). Obesity, diabetes mellitus (DM), hypertension,
      and hyperlipidemia were objectively assessed by self-reported history.
      Statistical analyses included univariate comparisons across sleep duration
      categories for all variables. Binary logistic regression analyses and
      cardiometabolic factor as outcome, with sleep duration category as predictor,
      were assessed with and without covariates. Observed relationships were further
      assessed for dependence on race/ethnicity. RESULTS: In adjusted analyses, very
      short sleep was associated with self-reported hypertension (odds ratio [OR],
      2.02, [95% confidence interval {CI},1.45-2.81]; P<0.0001), self-reported
      hyperlipidemia (OR, 1.96 [95% CI, 1.43-2.69]; P<0.0001), objective hyperlipidemia
      (OR, 1.41 [95% CI, 1.04-1.91]; P=0.03), self-reported DM (OR, 1.76 [95% CI, 1.13
      2.74]; P=0.01), and objective obesity (OR, 1.53 [95% CI, 1.03-1.43]; P=0.005).
      Regarding short sleep (5-6 h), in adjusted analyses, elevated risk was seen for
      self-reported hypertension (OR, 1.22 [95% CI, 1.02-1.45]; P=0.03) self-reported
      obesity (OR, 1.21 [95% CI, 1.03-1.43]; P=0.02), and objective obesity (OR, 1.17
      [95% CI, 1.00-1.38]; P<0.05). Regarding long sleep (>=9 h), no elevated risk was
      found for any outcomes. Interactions with race/ethnicity were significant for all
      outcomes; race/ethnicity differences in patterns of risk varied by outcome
      studied. In particular, the relationship between very short sleep and obesity was
      strongest among blacks and the relationship between short sleep and hypertension
      is strongest among non-Hispanic whites, blacks, and non-Mexican
      Hispanics/Latinos. CONCLUSIONS: Short sleep duration is associated with self
      reported and objectively determined adverse cardiometabolic outcomes, even after
      adjustment for many covariates. Also, these patterns of risk depend on
      race/ethnicity.

PMID- 24333225
TI  - Clark's nutcracker spatial memory: the importance of large, structural cues.
AB  - Clark's nutcrackers, Nucifraga columbiana, cache and recover stored seeds in high
      alpine areas including areas where snowfall, wind, and rockslides may frequently
      obscure or alter cues near the cache site. Previous work in the laboratory has
      established that Clark's nutcrackers use spatial memory to relocate cached food.
      Following from aspects of this work, we performed experiments to test the
      importance of large, structural cues for Clark's nutcracker spatial memory. Birds
      were no more accurate in recovering caches when more objects were on the floor of
      a large experimental room nor when this room was subdivided with a set of panels.
      However, nutcrackers were consistently less accurate in this large room than in a
      small experimental room. Clark's nutcrackers probably use structural features of
      experimental rooms as important landmarks during recovery of cached food. This
      use of large, extremely stable cues may reflect the imperfect reliability of
      smaller, closer cues in the natural habitat of Clark's nutcrackers. This article
      is part of a Special Issue entitled: CO3 2013. 

PMID- 24333226
TI  - Familiarity with the experimenter influences the performance of Common ravens
      (Corvus corax) and Carrion crows (Corvus corone corone) in cognitive tasks.
AB  - When humans and animals interact with one another over an extended time span they
      familiarise and may develop a relationship, which can exert an influence on both
      partners. For example, the behaviour of an animal in experiments may be affected
      by its relationship to the human experimenter. However, few studies have
      systematically examined the impact of human-animal relationships on experimental
      results. In the present study we investigated if familiarity with a human
      experimenter influences the performance of Common ravens (Corvus corax) and
      Carrion crows (Corvus corone corone) in interactive tasks. Birds were tested in
      two interactive cognitive tasks (exchange, object choice) by several
      experimenters representing different levels of familiarity (long and short-term).
      Our findings show that the birds participated more often in both tasks and were
      more successful in the exchange task when working with long-term experimenters
      than when working with short-term experimenters. Behavioural observations
      indicate that anxiety did not inhibit experimental performance but that the
      birds' motivation to work differed between the two kinds of experimenters,
      familiar and less familiar. We conclude that human-animal relationships (i.e.
      familiarity) may affect the experimental performance of corvids in interactive
      cognitive tasks. 

PMID- 24333227
TI  - Extraction, characterization and antioxidant property of chitosan from cuttlebone
      Sepia kobiensis (Hoyle 1885).
AB  - Chitin was extracted from the cuttlebone of Sepia kobiensis and chitosan was
      prepared through deacetylation. The chitosan was characterized for its
      structural, physical and thermal (CHN, DDA, FT-IR, NMR, XRD, Viscometric
      analysis, SEM and DSC) properties. Further, the chitosan exhibited the
      antioxidant activity of 50.68-74.36% at 1-10 mg ml(-1) and it also showed the
      reducing power of 0.28% at 1 mg ml(-1). At 10 mg ml(-1), the chitosan exhibited
      the scavenging ability of 46.17%, on 1,1-diphenyl-2-picrylhydrazyl radicals,
      23.38-73.70% on superoxide radicals at 0.05-1.6 mg ml(-1) and 18.34% to 62.39%
      (0.1-3.2 mg ml(-1)) on hydroxyl radicals; whereas at 1-10 mg ml(-1) the chelating
      ability on ferrous ions was calculated as 49.74-73.59%. Based on the potential
      antioxidant activity, scavenging ability on hydroxyl radicals and chelating
      abilities on ferrous ions, the chitosan from the cuttlebone of S. kobiensis may
      not only be used as a potent natural antioxidant but also as a possible food
      quality enhancer ingredient in the pharmaceutical industry.

PMID- 24333228
TI  - Identification and characterization of Euphorbia nivulia latex proteins.
AB  - The protein profile of latex of Euphorbia nivulia Buch.-Ham. is established.
      Three new proteins viz., Nivulian-I, II and III have been purified to homogeneity
      from the latex. The relative molecular masses of Nivulian-I, II and III are
      31,486.985, 43,670.846 and 52,803.470 Da respectively. Nivulian-I is a simple
      type of protein while Nivulian-II and III are glycoproteins. Peptide mass
      fingerprint analysis revealed peptides of these proteins match with Tubulin alpha
      1 chain of Eleusine indica, Maturase K of Banksia quercifolia and hypothetical
      protein of Zea mays respectively. Tryptic digestion profile of Nivulian-I, II and
      III, infer the exclusive nature of latex origin proteins and may be new and are
      additive molecules in the dictionaries of phytoproteins or botany. This is the
      first of its kind, regarding characterization and validation of Nivulian-I, II
      and III with respect to peptide sequencing.

PMID- 24333229
TI  - IL-18 levels in the semen of male infertility: semen analysis.
AB  - This study investigated the relationship between interleukin (IL)-18 levels and
      male infertility. Semen samples from 57 infertile and normal males were subjected
      to semen analysis. The pH of the semen samples from normal and abnormal groups
      showed no significant difference (p>0.05). However, semen volume, density,
      forward movement percentage, activity, survival rate, and normal morphology rate
      of the sperms in the normal group were significantly higher than those of the
      abnormal group (p<0.01). The IL-18 levels of semen in the abnormal group (810.91
      pg/mL) were higher than that of the normal group (402.74 pg/mL; p<0.01). Analyses
      indicate that seminal fluid IL-18 positively correlates with IL-6, IL-8, and
      tumor necrosis factor-alpha. Seminal IL-18 level does not affect bacterial colony
      count. Results indicate that IL-18 may be important in male reproduction.

PMID- 24333230
TI  - alpha-Glucosidase inhibition by luteolin: kinetics, interaction and molecular
      docking.
AB  - alpha-Glucosidase is a critical associated enzyme with type 2 diabetes mellitus
      in humans. Inhibition of alpha-glucosidase is important due to the potential
      effect of down regulating glucose absorption in patients. In this study, the
      inhibitory activity of flavone luteolin on alpha-glucosidase and their
      interaction mechanism were investigated by multispectroscopic methods along with
      molecular docking technique. It was found that luteolin reversibly inhibited
      alpha-glucosidase in a noncompetitive manner with an IC50 value of (1.72 +/-
      0.05) * 10(-4) mol L(-1), and the inhibition followed a multi-phase kinetic
      process with a first-order reaction. Luteolin had a strong ability to quench the
      intrinsic fluorescence of alpha-glucosidase through a static quenching procedure.
      The positive values of enthalpy and entropy change suggested that the binding of
      luteolin to alpha-glucosidase was driven mainly by hydrophobic interactions, and
      the binding distance was estimated to be 4.56 nm. Analysis of synchronous
      fluorescence, circular dichroism, and Fourier transform infrared spectra
      demonstrated that the binding of luteolin to alpha-glucosidase induced
      rearrangement and conformational changes of the enzyme. Moreover, the results
      obtained from molecular docking indicated that luteolin had a high affinity close
      to the active site pocket of alpha-glucosidase and indirectly inhibited the
      catalytic activity of the enzyme.

PMID- 24333231
TI  - Effective use of transdermal drug delivery in children.
AB  - Transdermal administration offers a non-invasive and convenient method for
      paediatric drug delivery. The competent skin barrier function in term infants and
      older children limits both water loss and the percutaneous entry of chemicals
      including drugs; but the smaller doses required by children eases the attainment
      of therapeutic concentrations. Transdermal patches used in paediatrics include
      fentanyl, buprenorphine, clonidine, scopolamine, methylphenidate, oestrogens,
      nicotine and tulobuterol. Some patches have paediatric labelling supported by
      clinical trials whereas others are used unlicensed. Innovative drug delivery
      methods, such as microneedles and sonophoresis are being tested for their safety
      and efficacy; needleless injectors are primarily used to administer growth
      hormone; and two iontophoretic devices were approved for paediatrics. In
      contrast, the immature and rapidly evolving skin barrier function in premature
      neonates represents a significant formulation challenge. Unfortunately, this
      population group suffers from an absence of approved transdermal formulations, a
      shortcoming exacerbated by the significant risk of excessive drug exposure via
      the incompletely formed skin barrier. 

PMID- 24333232
TI  - Three-dimensional preoperative virtual planning and template use for surgical
      correction of craniosynostosis.
AB  - BACKGROUND: Surgical correction of craniosynostosis aims to remodel the cranial
      vault to achieve a morphology approaching that of age-matched norms. However,
      current surgical technique is highly subjective and based largely on the
      surgeon's artistic vision in creating a normal head shape. Here, we present our
      technique and report our experience with the use of virtual surgery using
      computer-assisted design (CAD)/computer-assisted manufacturing (CAM) techniques
      to create a prefabricated template for the planning of osteotomies and the
      placement of bone segments, to achieve standardised, objective and precise
      correction of craniosynostosis. METHODS: Four patients who underwent cranial
      vault remodelling (CVR; three metopic synostosis and one sagittal synostosis)
      underwent virtual surgical planning (VSP) preoperatively using CAD/CAM
      techniques. VSP allows pre-planning of osteotomies to achieve the desired cranial
      vault shape. Surgical osteotomies and placement of bone segments were performed
      intra-operatively based on prefabricated templates. RESULTS: All patients
      demonstrated markedly improved head shape postoperatively. One patient developed
      a subdural haematoma 6 weeks postoperatively subsequent to a fall where he hit
      his head. The haematoma was drained and a soft spot was present in that location
      3 months postoperatively. CONCLUSION: The use of virtual surgery and
      prefabricated cutting guides allows for a more precise and rapid reconstruction.
      Surgical osteotomies are pre-planned and rapidly performed using a template, and
      precise placement of calvarial bone segments is achieved without the need for
      subjective assessment of the desired calvarial shape. In addition, patients and
      families have a significantly better understanding of the disease process and
      anticipated surgery preoperatively with the visualisation achieved through
      virtual surgery. This results in better alignment of hopes and expectations
      between the parents and surgeons.

PMID- 24333233
TI  - Treatment of postpneumonectomy syndrome with tissue expanders: the Great Ormond
      Street Hospital experience.
AB  - Postpneumonectomy syndrome (PPS) is a rare syndrome whereby the airway and
      oesophagus become obstructed due to extreme rotation of the mediastinum after
      pneumonectomy. Our treatment of this condition involved mediastinal repositioning
      and placement of a saline filled tissue expander into the pleural space. This has
      not been reported in the plastic surgical literature and we describe technical
      difficulties and how they were overcome. 

PMID- 24333234
TI  - Utilization of an ex vivo human placental perfusion model to predict potential
      fetal exposure to carboplatin during pregnancy.
AB  - OBJECTIVE: The objective of this study was to determine the fetal drug
      compartment concentrations when various concentrations of carboplatin cross the
      placental-trophoblastic barrier and the effect on the fetal kidneys. STUDY
      DESIGN: An ex vivo human placenta perfusion model was utilized. Term human
      placentae (n = 9) were collected immediately after delivery and then reperfused
      with plasma concentrations achieved with carboplatin an area under the curve of 5
      (1000 ng/mL), 7.5 (5000 ng/mL), or 11 (11,000 ng/mL). Antipyrine was used as a
      reference compound. Samples were collected over 2 hours. Placental transfer was
      evaluated by computation of transport fraction and clearance index. Primary cells
      isolated by explant culture of 16-18 week old fetal organ tissues were incubated
      with carboplatin for up to 48 hours with untreated cell as controls.
      Immunohistochemical, flow cytometry analysis, and immunoblotting were applied for
      the expression of apoptosis-related proteins. RESULTS: Mean transport fractions
      for carboplatin at low, middle, and high concentrations were 0.05 +/- 0.02, 0.04
      +/- 0.01, and 0.10 +/- 0.01, respectively, with clearance indexes of 0.22 +/-
      0.01, 0.14 +/- 0.08, and 0.50 +/- 0.07, respectively. The fetal peak
      concentrations of carboplatin achieved were 61 +/- 39 ng/mL (low), 375 +/- 248
      ng/mL (middle), and 2081 +/- 529 ng/mL (high). Fetal kidney cells exposed to
      carboplatin showed a concentration-dependent increased expression of apoptosis
      inducing factor and p53 apoptosis proteins and a time-dependent increase in
      expression Bax apoptosis protein expression. Apoptosis was confirmed at the high
      concentration by flow cytometry. CONCLUSION: Doses of carboplatin up to an area
      under the curve of 7.5 were not associated with significant placental transfer,
      fetal exposure, or fetal toxic effects. This suggests it might not be necessary
      to empirically reduce carboplatin doses in pregnant women.

PMID- 24333235
TI  - Cost and clinical utility of repeated syphilis screening in the third trimester
      in a high-risk population.
AB  - OBJECTIVE: We sought to determine the clinical utility and cost of repeating
      syphilis testing in the third trimester of pregnancy in a high-risk urban
      population. STUDY DESIGN: A retrospective cohort analysis was performed for
      patients delivering from January 1993 through December 2009 with at least 1
      venereal disease research laboratory (VDRL) test sent during pregnancy. Chart
      review was performed for patients with confirmed syphilis to determine the
      temporal relationship of syphilis diagnosis to the pregnancy. For patients who
      seroconverted during pregnancy (no antecedent history or treatment for syphilis),
      newborn charts were reviewed. The costs of treating seropositive neonates and the
      costs of implementing additional third-trimester syphilis screening were then
      compared. RESULTS: In the 17-year cohort, 58,569 deliveries were available for
      analysis. In all, 113 new cases of syphilis occurred (192.9/100,000 deliveries).
      There were 17 detected seroconversions; 10 were not rescreened in the third
      trimester and tested positive at delivery. These 10 patients may have benefitted
      from implementing uniform VDRL testing at 28-32 weeks' gestation. All newborns
      were asymptomatic with a negative workup and received empiric penicillin therapy.
      Based on 2011 hospital charges, the cost of evaluating and treating a neonate for
      syphilis is $11,079. Implementing an additional VDRL screen at 28-32 weeks'
      gestation for each pregnant patient during the 17 years studied would cost
      $1,991,346. An 18-fold increase in syphilis prevalence (3500/100,000 [3.5%]
      deliveries) would be required for the cost of implementation of universal early
      third-trimester screening to be equal to the potential health care charges saved
      by detecting maternal seroconversion and obviating the need for neonatal therapy.
      CONCLUSION: In this high-risk population, additional syphilis screening in the
      third trimester is costly and is not clinically helpful in detecting maternal
      seroconversion.

PMID- 24333236
TI  - Acute endocrine and nutritional co-regulation of the hepatic omy-miRNA-122b and
      the lipogenic gene fas in rainbow trout, Oncorhynchus mykiss.
AB  - Hepatic lipogenesis represents a crucial part of intermediary metabolism and is
      acutely regulated by endocrine factors and nutrients. The liver-specific and
      highly abundant microRNA-122 has emerged as a powerful regulator of lipogenesis
      in higher vertebrates, but little is known about its endocrine and nutritional
      regulation. In this study, we investigated the hypothesis that insulin regulates
      hepatic expression of omy-miRNA-122 isomiRNAs (omy-miRNA-122a and omy-miRNA-122b)
      by using in vivo and in vitro approaches. Since the hepatic insulin pathway and
      lipogenesis are acutely regulated by dietary macronutrient ratios in rainbow
      trout, we further investigated the effect of single meals with altered
      carbohydrate/protein ratio and lipid/protein ratio on the postprandial expression
      of omy-miRNA-122 isomiRNAs. Insulin acutely induced omy-miRNA-122b expression in
      vivo and in vitro. Conversely, a single meal with increased lipid to protein
      ratio acutely decreased expression of both omy-miRNA-122 isomiRNAs. As a direct
      proof of lipogenic effects of miRNA-122 is currently still lacking in fish, we
      investigated the correlated expression between omy-miRNA-122 isomiRNAs and the
      rate-limiting lipogenic gene fas, an indirect target gene of miRNA-122 in
      mammals. Our results show a significant positive correlation of omy-miRNA-122b
      and fas, consistent with a potential evolutionary conserved role for miRNA-122 in
      the regulation of postprandial lipogenesis in trout. 

PMID- 24333238
TI  - Feasibility and validity of early screening for identifying infants with poor
      social-communication development in a well-baby clinic system.
AB  - This study examined the feasibility and validity of implementing an autism
      spectrum disorders (ASD) screening for 12-month-old infants. METHOD: Parents of
      583 infants, 12months of age attending well baby clinics (WBCs), completed the
      First Year Inventory-Lite (FYI-L). Ten infants who failed the FYI-L and a subset
      of 12 infants who passed the identified FYI-L were evaluated using the Autism
      Observation Scale for Infants (AOSI) and the Mullen Scales of Early Learning.
      Information regarding social-communication development >=24months of age was
      extracted from medical records of 153 of the 583 infants. RESULTS: Mean response
      rate across clinics was 26.63%. Infants at risk compared to controls showed
      significantly higher scores on the AOSI, lower composite scores on the MSEL, and
      a higher rate of referral for a developmental evaluation. At 24months, 95% of
      infants who were negatively screened had no social-communication problems on
      their medical records; 60% of those who were screened positive had documented
      problems on medical records. CONCLUSION: ASD screening using the FYI-L at
      12months in a healthcare setting identifies infants with poor social
      communication development, yet parents had low compliance with screening.

PMID- 24333237
TI  - Protein markers for identification of Yersinia pestis and their variation related
      to culture.
AB  - The detection of high consequence pathogens, such as Yersinia pestis, is well
      established in biodefense laboratories for bioterror situations. Laboratory
      protocols are well established using specified culture media and a growth
      temperature of 37  degrees C for expression of specific antigens. Direct
      detection of Y. pestis protein markers, without prior culture, depends on their
      expression. Unfortunately protein expression can be impacted by the culture
      medium which cannot be predicted ahead of time. Furthermore, higher biomass
      yields are obtained at the optimal growth temperature (i.e. 28  degrees C-30 
      degrees C) and therefore are more likely to be used for bulk production. Analysis
      of Y. pestis grown on several types of media at 30  degrees C showed that several
      protein markers were found to be differentially detected in different media.
      Analysis of the identified proteins against a comprehensive database provided an
      additional level of organism identification. Peptides corresponding to variable
      regions of some proteins could separate large groups of strains and aid in
      organism identification. This work illustrates the need to understand variability
      of protein expression for detection targets. The potential for relating
      expression changes of known proteins to specific media factors, even in nutrient
      rich and chemically complex culture medium, may provide the opportunity to draw
      forensic information from protein profiles. 

PMID- 24333239
TI  - Identification, prevention, and treatment of children with decreased bone mineral
      density.
AB  - Osteoporosis in children is the presence of decreased bone mineral density in
      association with a significant fracture history. The amount of bone accretion in
      childhood and early adulthood is predictive of the risk of osteoporosis and
      fracture in later adulthood. A myriad of disorders and medications are associated
      with decreased bone mineral density in childhood. In addition, lifestyle factors
      including poor dietary habits and minimal physical activity are associated with
      low bone mass. Because of the limited attention given to childhood osteoporosis,
      this review was undertaken to examine the diagnostic criteria, etiologies,
      prevention of and treatment strategies for osteoporosis in children and
      adolescents. 

PMID- 24333240
TI  - Intrarenal and extrarenal autonomic nervous system redefined.
AB  - PURPOSE: The autonomic nervous supply to the kidneys is involved in the
      development of several diseases including hypertension. The neural distribution
      at the segmental vessels and intrarenal vasculature has not been well
      characterized. Thus, we evaluated the autonomic nerve distribution from the great
      vessels to the renal cortex in a cadaveric model. MATERIALS AND METHODS: We
      performed a detailed anatomical nerve dissection from the inferior mesenteric
      artery to the renal operculum in 2 human cadaveric torsos. Autonomic nerve fibers
      were verified by dissecting the greater splanchnic, sympathetic trunk and
      ganglia. We then systematically cross-sectioned the kidneys in 12, 1 mm slices
      across 3.6 cm, and stained the slices for histopathological analysis of neural
      tissue in relation to segmental arteries and other anatomical landmarks. Advanced
      reconstructive software was used to create a 3-dimensional computer image.
      RESULTS: Autonomic nerve fibers are located almost exclusively anteriorly on the
      main renal arteries and segmental arteries, and are absent from veins.
      Histopathology revealed that the intrarenal nerves continued to track exclusively
      with the arteries but were more circumferentially distributed. There is minimal
      nerve tissue around the veins. Many nerves were within a few millimeters of the
      renal collecting system. CONCLUSIONS: The autonomic nerves supplying the kidney
      maintain their distribution almost exclusively along the anterior surface of
      arteries as they pass from the aorta to the segmental arteries. Once inside the
      renal parenchyma, the nerves are circumferentially distributed around the renal
      arteries and are in close proximity to the renal collecting system.

PMID- 24333241
TI  - Urinary PCA3 as a predictor of prostate cancer in a cohort of 3,073 men
      undergoing initial prostate biopsy.
AB  - PURPOSE: PCA3 is a urinary marker that has shown promise in predicting the
      presence of prostate cancer in men undergoing repeat prostate biopsy. We studied
      PCA3 before initial prostate biopsy. MATERIALS AND METHODS: Records from a single
      organization were retrospectively reviewed. The predictive value of PCA3 was
      explored using nonparametric receiver operating characteristic curve analysis
      (ROC) and multivariable logistic regression analysis. RESULTS: A total of 3,073
      men underwent PCA3 analysis before initial prostate biopsy sampling of 12 to 14
      areas. Mean PCA3 was 27.2 and 52.5 for patients without and with cancer,
      respectively. Prostate cancer was identified in 1,341 (43.6%) men. Overall 54.5%
      had Gleason 6 disease and 45.5% had Gleason 7 or greater (high grade prostate
      cancer). Mean PCA3 was 47.5 and 58.5 for the patients with Gleason 6 and 7 or
      greater disease, respectively. On multivariable logistic analysis PCA3 was
      statistically significantly associated with prostate cancer and high grade
      prostate cancer after adjusting for prostate specific antigen (p<0.001 for both),
      free prostate specific antigen (p=0.04 and p=0.01, respectively), age (p<0.001
      for both), family history (p<0.001 and p=0.59, respectively), abnormal digital
      rectal examination (p=0.31 and p<0.001, respectively), prostate volume (p<0.001
      for both) and body mass index (p<0.001 for both). Using ROC analysis PCA3
      outperformed prostate specific antigen in the prediction of prostate cancer (AUC
      0.697 vs 0.599, p<0.01) but not for high grade prostate cancer (AUC 0.682 vs
      0.679, p=0.702). CONCLUSIONS: PCA3 proved a useful tool in identifying patients
      at risk for prostate cancer before initial prostate biopsy. To our knowledge this
      is the largest PCA3 study in the initial biopsy population. These results suggest
      that further exploration of the value of PCA3 is warranted.

PMID- 24333242
TI  - Intracorporeal robot-assisted microsurgical vasovasostomy for the treatment of
      bilateral vasal obstruction occurring following bilateral inguinal hernia repairs
      with mesh placement.
AB  - PURPOSE: Various surgical approaches have been described to manage iatrogenic
      inguinal vasal obstruction, including open microscopic, laparoscopic and robot
      assisted techniques. The open and laparoscopic approaches are often limited in
      cases of extensive inguinal obstruction or inadequate intra-abdominal vasal
      length. The robotic approach offers novel opportunities to the operating surgeon,
      including performing microsurgical anastomoses in traditionally challenging
      locations. To our knowledge we describe the first intracorporeal robot-assisted,
      microsurgical vasovasostomy for iatrogenic vasal obstruction not amenable to
      standard microscopic repair. MATERIALS AND METHODS: Bilateral intracorporeal
      robot-assisted microsurgical vasovasostomy was performed. The proximal vasa were
      transected and obstruction of the distal segments was confirmed. After docking
      the robot the intracorporeal regions of the vasa were transected at the internal
      ring. The proximal vasal segments were passed intracorporeally and approximated
      with 5-zero polypropylene sutures. A standard 2-layer anastomosis was performed
      intracorporeally using 10-zero/9-zero sutures. RESULTS: Total operative time was
      278 minutes. No intraoperative or postoperative complications were noted. Semen
      analysis 8 weeks after the procedure demonstrated a total volume of 5.4 cc, 8.4 *
      10(6) sperm per ml, 45.4 * 10(6) total sperm and 16% motility, consistent with a
      successful result. CONCLUSIONS: To our knowledge this represents the first
      reported case of intracorporeal outpatient vasovasostomy. These results
      demonstrate the feasibility of the procedure and highlight unique aspects of the
      robotic approach, which may offer advantages over the traditional microscope in
      select cases.

PMID- 24333243
TI  - Impact of ABO blood type on outcomes in patients with primary nonmuscle invasive
      bladder cancer.
AB  - PURPOSE: ABO blood type is an established prognostic factor for several
      malignancies but its role in bladder urothelial carcinoma is largely unknown. We
      determined whether ABO blood type is associated with the outcome of transurethral
      resection of nonmuscle invasive bladder urothelial carcinoma. MATERIALS AND
      METHODS: We retrospectively studied ABO blood types in 931 patients with primary
      nonmuscle invasive bladder urothelial carcinoma treated with transurethral
      bladder resection with or without intravesical instillation therapy. Disease
      recurrence and progression were analyzed with univariable and multivariable
      competing risks regression models. Median followup was 67 months. Discrimination
      was evaluated by the concordance index. RESULTS: The ABO blood type was O, A, B
      and AB in 414 (44.5%), 360 (38.7%), 103 (11.1%) and 54 patients (5.8%),
      respectively. ABO blood type was significantly associated with outcome on
      univariable and multivariable analysis. Overall, patients with blood type O had
      worse recurrence and progression rates than those with A (p = 0.015 and 0.031) or
      B (p = 0.004 and 0.075, respectively). The concordance index of multivariable
      base models increased after including ABO blood type. CONCLUSIONS: In patients
      with nonmuscle invasive bladder urothelial carcinoma the ABO blood type may
      predict the outcome. Those with blood type O showed the highest recurrence and
      progression rates. Including ABO blood type in multivariable models increases the
      accuracy of standard prognostic factors. Since the ABO blood type is available
      for most patients, it may represent an ideal adjunctive marker to predict
      recurrence and progression. The biological explanation and prognostic value of
      this finding must be further elucidated.

PMID- 24333244
TI  - Monopolar versus bipolar transurethral resection of bladder tumors: a single
      center, parallel arm, randomized, controlled trial.
AB  - PURPOSE: We compared the safety and efficacy of bipolar transurethral resection
      and monopolar resection for bladder tumors. MATERIALS AND METHODS: A single
      center, parallel arm, randomized, controlled trial was performed from May 2011 to
      August 2012. All patients with suspected bladder tumors were eligible for study
      inclusion. Those who refused consent and those undergoing routine restaging
      transurethral resection of bladder tumor were excluded from analysis. The primary
      end point was the incidence of obturator jerk. Secondary study outcomes included
      the decrease in hematocrit, rates of recoagulation and transfusion, bladder
      perforation, decrease in sodium, resection syndrome and resection time.
      Pathological quality was assessed by comparing deep muscle and the degree of
      severe cautery artifact in the 2 arms. RESULTS: A total of 257 transurethral
      resections were performed during the study period. After exclusion 147 patients
      were randomized, including 75 in the monopolar arm and 72 in the bipolar arm.
      There were 6 and 4 protocol violations in the monopolar and bipolar arms,
      respectively. Intent to treat and per protocol analyses were performed. The
      incidence of obturator jerk was greater in the bipolar arm (60% vs 49.2%,
      p=0.27). There was no significant difference between secondary outcomes. The only
      significant difference was a significantly lower incidence of severe cautery
      artifact in the bipolar arm (25% vs 46.7%, p=0.0096). CONCLUSIONS: Bipolar
      transurethral resection of bladder tumor was not superior to monopolar resection
      with respect to obturator jerk, bladder perforation and hemostasis. There was a
      significantly lower incidence of severe cautery artifact after bipolar resection.

PMID- 24333245
TI  - Influencing factors leading to malpractice litigation in radical prostatectomy.
AB  - PURPOSE: The litigious nature of the medical-legal environment is a major concern
      for American physicians with an estimated cost of $10 billion. In this study we
      identify the causes of litigation in cases of radical prostatectomy as well as
      the factors that contribute to verdicts or settlements resulting in indemnity
      payments. MATERIALS AND METHODS: Publicly available verdict reports were recorded
      using the Westlaw(r) legal database. To identify pertinent cases we used the
      search terms "medical malpractice" and "prostate" or "prostatectomy" with dates
      ranging from 2000 to 2013. Cases were evaluated for alleged cause of malpractice,
      resulting injury, findings and indemnity payment (if any). RESULTS: The database
      search yielded 222 cases, with 25 being relevant to radical prostatectomy. Of
      these cases 24.0% were settled out of court and the remaining 76.0% went to
      trial. Of those cases that went to trial 20.8% saw patients awarded damages.
      There was no significant difference in awards between verdict and settlement.
      Overall 36.0% of patients claimed that they did not receive proper informed
      consent and 16.0% claimed that the surgery was not the proper standard of care.
      Thirteen of the cases claimed negligence in the performance of the surgery with
      the bulk of these claims being the result of rectal perforation. CONCLUSIONS: The
      main issues that arise in radical prostatectomy malpractice litigation are those
      of informed consent and clinical performance. Comprehensive preoperative
      counseling, when combined with proper surgical technique, may minimize the impact
      of litigation.

PMID- 24333246
TI  - A rapid, efficient, and economical inverse polymerase chain reaction-based method
      for generating a site saturation mutant library.
AB  - With the development of deep sequencing methodologies, it has become important to
      construct site saturation mutant (SSM) libraries in which every nucleotide/codon
      in a gene is individually randomized. We describe methodologies for the rapid,
      efficient, and economical construction of such libraries using inverse polymerase
      chain reaction (PCR). We show that if the degenerate codon is in the middle of
      the mutagenic primer, there is an inherent PCR bias due to the thermodynamic
      mismatch penalty, which decreases the proportion of unique mutants. Introducing a
      nucleotide bias in the primer can alleviate the problem. Alternatively, if the
      degenerate codon is placed at the 5' end, there is no PCR bias, which results in
      a higher proportion of unique mutants. This also facilitates detection of
      deletion mutants resulting from errors during primer synthesis. This method can
      be used to rapidly generate SSM libraries for any gene or nucleotide sequence,
      which can subsequently be screened and analyzed by deep sequencing. 

PMID- 24333247
TI  - A chromogenic assay for limit dextrinase and pullulanase activity.
AB  - A new chromogenic substrate to assay the starch debranching enzymes limit
      dextrinase and pullulanase is described. The 2-chloro-4-nitrophenyl glycoside of
      a commercially available branched heptasaccharide (Glc-maltotriosyl-maltotriose)
      was found to be a suitable specific substrate for starch debranching enzymes and
      allows convenient assays of enzymatic activities in a format suited for high
      throughput analysis. The kinetic parameters of these enzymes toward the
      synthesized substrate are determined, and the selectivity of the substrate in a
      complex cereal-based extract is established. 

PMID- 24333248
TI  - Generating NMR chemical shift assignments of intrinsically disordered proteins
      using carbon-detected NMR methods.
AB  - There is an extraordinary need to describe the structures of intrinsically
      disordered proteins (IDPs) due to their role in various biological processes
      involved in signaling and transcription. However, general study of IDPs by NMR
      spectroscopy is limited by the poor (1)H amide chemical shift dispersion
      typically observed in their spectra. Recently, (13)C direct-detected NMR
      spectroscopy has been recognized as enabling broad structural study of IDPs. Most
      notably, multidimensional experiments based on the (15)N,(13)C CON spectrum make
      complete chemical shift assignment feasible. Here we document a collection of NMR
      based tools that efficiently lead to chemical shift assignment of IDPs, motivated
      by a case study of the C-terminal disordered region from the human pancreatic
      transcription factor Pdx1. Our strategy builds on the combination of two three
      dimensional (3D) experiments, (HN-flip)N(CA)CON and 3D (HN-flip)N(CA)NCO, that
      enable daisy chain connections to be built along the IDP backbone, facilitated by
      acquisition of amino acid-specific (15)N,(13)C CON-detected experiments.
      Assignments are completed through carbon-detected, total correlation spectroscopy
      (TOCSY)-based side chain chemical shift measurement. Conducting our study
      required producing valuable modifications to many previously published pulse
      sequences, motivating us to announce the creation of a database of our pulse
      programs, which we make freely available through our website. 

PMID- 24333249
TI  - Maximizing exosome colloidal stability following electroporation.
AB  - Development of exosome-based semisynthetic nanovesicles for diagnostic and
      therapeutic purposes requires novel approaches to load exosomes with cargo.
      Electroporation has previously been used to load exosomes with RNA. However,
      investigations into exosome colloidal stability following electroporation have
      not been considered. Herein, we report the development of a unique trehalose
      pulse media (TPM) that minimizes exosome aggregation following electroporation.
      Dynamic light scattering (DLS) and RNA absorbance were employed to determine the
      extent of exosome aggregation and electroextraction post electroporation in TPM
      compared to common PBS pulse media or sucrose pulse media (SPM). Use of TPM to
      disaggregate melanoma exosomes post electroporation was dependent on both exosome
      concentration and electric field strength. TPM maximized exosome dispersal post
      electroporation for both homogenous B16 melanoma and heterogeneous human serum
      derived populations of exosomes. Moreover, TPM enabled heavy cargo loading of
      melanoma exosomes with 5nm superparamagnetic iron oxide nanoparticles (SPION5)
      while maintaining original exosome size and minimizing exosome aggregation as
      evidenced by transmission electron microscopy. Loading exosomes with SPION5
      increased exosome density on sucrose gradients. This provides a simple, label
      free means of enriching exogenously modified exosomes and introduces the
      potential for MRI-driven theranostic exosome investigations in vivo. 

PMID- 24333250
TI  - Analyzing transcription factor activity using near infrared fluorescent bridge
      polymerase chain reaction.
AB  - This study has developed a new method, near infrared fluorescent bridge
      polymerase chain reaction (NIRF-bPCR), for analyzing transcription factor (TF)
      activity. This method was first used to detect the activity of purified nuclear
      factor kappa B (NF-kappaB) p50. The results demonstrated that this method could
      quantitatively detect the activity of p50 protein at less than 115ng (~
      2320fmol), and the detection limit reached as little as 6.94ng (~ 140fmol) of p50
      protein. This method was then used to detect TF activity in cell extracts. The
      results revealed that this method could specifically detect NF-kappaB activity in
      HeLa cell nuclear extracts. Finally, this method was used to detect the
      activities of multiple TFs in a protein sample. The results showed that this
      method could detect the activities of six TFs-NF-kappaB, AP-1, TFIID, CREB, NF
      E2, and p53-in the TNFalpha-induced and -uninduced HeLa cell nuclear extracts.
      Calculation of the fold induction of six TFs revealed that NF-kappaB, CREB, and
      AP1 were activated by TNFalpha induction in HeLa cells, in agreement with the
      detection results of other methods. Therefore, this study provides a new tool for
      analyzing TF activity. This study also revealed that NIRF-bPCR may be used as a
      new method for detecting DNA molecules. 

PMID- 24333251
TI  - One-step homogeneous non-stripping chemiluminescence metal immunoassay based on
      catalytic activity of gold nanoparticles.
AB  - The catalytic activity of gold nanoparticles (AuNPs) on a luminol-H2O2
      chemiluminescence (CL) system is found to be greatly enhanced after its
      crosslinking aggregation induced by immunoreaction. Based on this observation, a
      one-step homogeneous non-stripping CL metalloimmunoassay was designed. In the
      presence of corresponding antigen (Ag), the immunoreaction caused the aggregation
      of antibody (Ab)-modified AuNPs, and these crosslinking aggregated AuNPs could
      catalyze luminol-H2O2 CL reaction to produce a much stronger CL signal than
      dispersed Ab-modified AuNPs. The assay, including immunoreaction and detection,
      can be accomplished in homogeneous solution. In the assay, no tedious and strict
      stripping of metal nanoparticles, difficult synthesis of labels, multiple steps
      of immunoreactions and washings, and complicated magnetic separation process were
      required. The detection limit of human immunoglobulin G (IgG, 3sigma) was
      estimated to be as low as 3.2*10(-11) g ml(-1). The sensitivity was increased by
      two orders of magnitude over that of other AuNP-based CL immunoassay. The current
      CL metalloimmunoassay offers the advantages of being simple, cheap, rapid, and
      sensitive.

PMID- 24333252
TI  - Phosphorylation of multifunctional galectins by protein kinases CK1, CK2, and
      PKA.
AB  - Phosphorylation is known to have a strong impact on protein functions. We
      analyzed members of the lectin family of multifunctional galectins as targets of
      the protein kinases CK1, CK2, and PKA. Galectins are potent growth regulators
      able to bind both glycan and peptide motifs at intra- and extracellular sites.
      Performing in vitro kinase assays, galectin phosphorylation was detected by
      phosphoprotein staining and autoradiography. The insertion of phosphoryl groups
      varied to a large extent depending on the type of kinase applied and the
      respective galectin substrate. Sites of phosphorylation observed in the
      recombinant galectins were determined by a strategic combination of
      phosphopeptide enrichment and nano-ultra-performance liquid chromatography tandem
      mass spectrometry (nanoUPLC-MS/MS). By in silico modeling, phosphorylation sites
      were visualized three-dimensionally. Our results reveal galectin-type-specific
      Ser-/Thr-dependent phosphorylation beyond the known example of galectin-3. These
      data are the basis for functional studies and also illustrate the analytical
      sensitivity of the applied methods for further work on human lectins. 

PMID- 24333253
TI  - Hsp65 phylogenetic assay for molecular diagnosis of nontuberculous mycobacteria
      isolated in Mexico.
AB  - BACKGROUND AND AIMS: Nontuberculous mycobacteria (NTM) are mainly distributed as
      important emerging pathogens in patients with chronic or immunosuppressive
      diseases. Accurate identification of causative species is crucial for proper
      treatment and patient follow-up. However, several difficulties are associated
      with phenotypic and molecular diagnostic methods for precise identification at
      the species level due to shared metabolic and genetic characteristics. We
      undertook this study to evaluate the application of the phylogenetic method based
      on hsp65 gene into Telenti's PCR-restriction enzyme analysis (PRA) for molecular
      identification of NTM. METHODS: The study population was comprised of 1646
      Mycobacterium clinical isolates (AFB positive) collected from 2008-2011, of which
      537 (32.6%) were MNT identified by PRA analysis. DNA sequencing of hsp65 in 53
      isolates (10%) was performed. Sequence identification through NCBI-Basic Local
      Alignment Search Tool (BLAST) achieved correct identification in 23 isolates.
      Phylogenetic trees including hsp65 available GenBank sequences for all described
      genres of NTM and hsp65 obtained sequences were constructed using Mega 5.05
      software. We compared sequence identification based on phylogenetic clustering
      and BLAST similarity search. RESULTS: Phylogenetic clustering allowed more
      specific differentiation of closely related species and clearer identification in
      comparison with BLAST; 30 Mycobacterium species (this is the first report of
      isolation of some of these from clinical samples in Mexico) were identified in
      this way. CONCLUSIONS: The proposed 440 bp hsp65 phylogenetic method allows a
      better identification tool to differentiate Mycobacterium species and is useful
      to complement diagnosis and epidemiological surveillance of NTM.

PMID- 24333254
TI  - Statin use is not associated with presence of and severity of nonalcoholic fatty
      liver disease.
AB  - BACKGROUND AND AIMS: There is concern that statin use may exacerbate nonalcoholic
      fatty liver disease (NAFLD). We aimed to assess the association of statin use
      with NALFD and severity of liver fibrosis among NAFLD individuals. METHODS: We
      evaluated 6,385 cross-sectional healthy Brazilian subjects (43 +/- 10 years, 79%
      males) without clinical coronary heart disease between November 2008 and July
      2010. NAFLD was diagnosed by ultrasound. Severity of liver fibrosis was predicted
      by fatty liver index and FIB-4. RESULTS: NAFLD prevalence was 36% (n = 2310).
      Overall 552 (9%) individuals were using statins of whom 49% had NAFLD. Statin
      users were more likely to be men, older age, and have higher burden of risk
      factors (p <0.05). In age gender adjusted analysis the odds ratio for NAFLD with
      statin use was 0.87 (0.61-1.25, p = 0.46) in the presence of metabolic syndrome
      and 1.08 (0.88-1.32, p = 0.56) in its absence. On further adjustment for
      metabolic risk factors, LDL and smoking the results remained unchanged (OR: 0.89,
      95% CI: 0.65-1.32, p = 0.56 and 0.90 (0.69-1.18, p = 0.46). There was no
      significant association between statin use and fatty liver index in a subanalysis
      of NAFLD individuals (71 +/- 18 vs. 69 +/- 23, p = 0.18). Although FIB-4 was
      mildly elevated with statin use (1.20 +/- 0.51 vs. 1.02 +/- 0.46, p <0.001), a
      multivariate analysis adjusted for age, gender and risk factors revealed statin
      use was not associated with severe fibrosis (FIB >1.45) (OR 0.88, 95% CI: 0.60
      1.29, p = 0.50). CONCLUSIONS: The results of this study favor statin use in
      subjects with NAFLD as its use is not associated with the presence of NAFLD or
      increased fibrosis.

PMID- 24333256
TI  - Introduction of a methoxymethyl side chain into p-phenylenediamine attenuates its
      sensitizing potency and reduces the risk of allergy induction.
AB  - The strong sensitizing potencies of the most important primary intermediates of
      oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2
      methyl-PPD) are well established. They are considered as the key sensitizers in
      hair dye allergic contact dermatitis. While modification of their molecular
      structure is expected to alter their sensitizing properties, it may also impair
      their color performance. With introduction of a methoxymethyl side chain we found
      the primary intermediate 2-methoxymethyl-p-phenylenediamine (ME-PPD) with
      excellent hair coloring performance but significantly reduced sensitizing
      properties compared to PPD and PTD: In vitro, ME-PPD showed an attenuated innate
      immune response when analyzed for its protein reactivity and dendritic cell
      activation potential. In vivo, the effective concentration of ME-PPD necessary to
      induce an immune response 3-fold above vehicle control (EC3 value) in the local
      lymph node assay (LLNA) was 4.3%, indicating a moderate skin sensitizing potency
      compared to values of 0.1 and 0.17% for PPD and PTD, respectively. Finally,
      assessing the skin sensitizing potency of ME-PPD under consumer hair dye usage
      conditions through a quantitative risk assessment (QRA) indicated an allergy
      induction risk negligible compared to PPD or PTD. 

PMID- 24333255
TI  - Metalloproteins and phytochelatin synthase may confer protection against zinc
      oxide nanoparticle induced toxicity in Caenorhabditis elegans.
AB  - Zinc oxide nanoparticles (ZnONPs) are used in large quantities by the cosmetic,
      food and textile industries. Here we exposed Caenorhabditis elegans wild-type and
      a metal sensitive triple knockout mutant (mtl-1;mtl-2;pcs-1) to ZnONPs (0-50mg/L)
      to study strain and exposure specific effects on transcription, reactive oxygen
      species generation, the biomolecular phenotype (measured by Raman
      microspectroscopy) and key endpoints of the nematode life cycle (growth,
      reproduction and lifespan). A significant dissolution effect was observed, where
      dissolved ZnO constituted over 50% of total Zn within a two day exposure to the
      test medium, suggesting that the nominal exposure to pure ZnONPs represents in
      vivo, at best, a mixture exposure of ionic zinc and nanoparticles. Nevertheless,
      the analyses provided evidence that the metallothioneins (mtl-1 and mtl-2), the
      phytochelatin synthase (pcs-1) and an apoptotic marker (cep-1) were
      transcriptionally activated. In addition, the DCFH-DA assay provided in vitro
      evidence of the oxidative potential of ZnONPs in the metal exposure sensitive
      triple mutant. Raman spectroscopy highlighted that the biomolecular phenotype
      changes significantly in the mtl-1;mtl-2;pcs-1 triple knockout worm upon ZnONP
      exposure, suggesting that these metalloproteins are instrumental in the
      protection against cytotoxic damage. Finally, ZnONP exposure was shown to
      decrease growth and development, reproductive capacity and lifespan, effects
      which were amplified in the triple knockout. By combining diverse toxicological
      strategies, we identified that individuals (genotypes) housing mutations in key
      metalloproteins and phytochelatin synthase are more susceptible to ZnONP
      exposure, which underlines their importance to minimize ZnONP induced toxicity. 

PMID- 24333257
TI  - Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells
      for the detection of hepatotoxic drugs in humans.
AB  - Drug induced liver injury (DILI) is a major cause of attrition during early and
      late stage drug development. Consequently, there is a need to develop better in
      vitro primary hepatocyte models from different species for predicting
      hepatotoxicity in both animals and humans early in drug development. Dog is often
      chosen as the non-rodent species for toxicology studies. Unfortunately, dog in
      vitro models allowing long term cultures are not available. The objective of the
      present manuscript is to describe the development of a co-culture dog model for
      predicting hepatotoxic drugs in humans and to compare the predictivity of the
      canine model along with primary human hepatocytes and HepG2 cells. After rigorous
      optimization, the dog co-culture model displayed metabolic capacities that were
      maintained up to 2 weeks which indicates that such model could be also used for
      long term metabolism studies. Most of the human hepatotoxic drugs were detected
      with a sensitivity of approximately 80% (n=40) for the three cellular models.
      Nevertheless, the specificity was low approximately 40% for the HepG2 cells and
      hepatocytes compared to 72.7% for the canine model (n=11). Furthermore, the dog
      co-culture model showed a higher superiority for the classification of 5 pairs of
      close structural analogs with different DILI concerns in comparison to both human
      cellular models. Finally, the reproducibility of the canine system was also
      satisfactory with a coefficient of correlation of 75.2% (n=14). Overall, the
      present manuscript indicates that the dog co-culture model may represent a
      relevant tool to perform chronic hepatotoxicity and metabolism studies.

PMID- 24333258
TI  - Use of porcine vaginal tissue ex-vivo to model environmental effects on vaginal
      mucosa to toxic shock syndrome toxin-1.
AB  - Menstrual toxic shock syndrome (mTSS) is a rare, recognizable, and treatable
      disease that has been associated with tampon use epidemiologically. It involves a
      confluence of microbial risk factors (Staphylococcus aureus strains that produce
      the superantigen-TSST-1), as well as environmental characteristics of the vaginal
      ecosystem during menstruation and host susceptibility factors. This paper
      describes a series of experiments using the well-characterized model of porcine
      vaginal mucosa ex-vivo to assess the effect of these factors associated with
      tampon use on the permeability of the mucosa. The flux of radiolabeled TSST-1 and
      tritiated water ((3)H2O) through porcine vaginal mucosa was determined at various
      temperatures, after mechanical disruption of the epithelial surface by tape
      stripping, after treatment with surfactants or other compounds, and in the
      presence of microbial virulence factors. Elevated temperatures (42, 47 and 52
      degrees C) did not significantly increase flux of (3)H2O. Stripping of the
      epithelial layers significantly increased the flux of labeled toxin in a dose
      dependent manner. Addition of benzalkonium chloride (0.1 and 0.5%) and glycerol
      (4%) significantly increased the flux of (3)H2O but sodium lauryl sulfate at any
      concentration tested did not. The flux of the labeled toxin was significantly
      increased in the presence of benzalkonium chloride but not Pluronic(r) L92 and
      Tween 20 and significantly increased with addition of alpha-hemolysin but not
      endotoxin. These results show that the permeability of porcine vagina ex-vivo to
      labeled toxin or water can be used to evaluate changes to the vaginal environment
      and modifications in tampon materials, and thus aid in risk assessment. 

PMID- 24333259
TI  - Absence of amyloid-beta in lenses of Alzheimer patients: a confocal Raman
      microspectroscopic study.
AB  - We have compared the protein profiles in plaques and tangles in the hippocampus
      of post-mortem Alzheimer brains and in opaque and clear regions in the deep
      cortex of eye lenses of the same donors. From the 7 Alzheimer donors studied, 1
      had pronounced bilateral cortical lens opacities, 1 moderate and 5 only minor or
      no cortical opacities. We focused on beta-sheet levels, a hallmarking property of
      amyloid-beta, the major protein of plaques and tau protein, the major protein of
      tangles in Alzheimer brains. Confocal Raman microspectroscopy and imaging was
      used in combination with hierarchical cluster analysis. Plaques and tangles show
      high levels of beta-sheets with a beta-sheet to protein ratio of 1.67. This ratio
      is 1.12 in unaffected brain tissue surrounding the plaques and tangles. In the
      lenses this ratio is 1.17 independently of the presence or absence of opacities.
      This major difference in beta-sheet conformation between hippocampus and lens is
      supported by Congo red and immunostaining of amyloid-beta and tau which were
      positive for plaques and tangles in the hippocampus but fully negative for the
      lens irrespective of the presence or absence of opacities. In line with a
      previous study (Michael et al., 2013) we conclude that cortical lens opacities
      are not typical for Alzheimer patients and are not hallmarked by accumulation of
      amyloid-beta, and can thus not be considered as predictors or indicators of
      Alzheimer disease as claimed by Goldstein et al. (2003). 

PMID- 24333260
TI  - New furoquinoline alkaloids from the leaves of Evodia lepta.
AB  - Three new furoquinoline alkaloids, leptanoines A-C (1-3) along with three known
      compounds (4-6) were isolated from the leaves of Evodia lepta. Their structures
      were identified by interpretation of their spectroscopic data as well as
      comparison with those reported in the literature. In addition, all isolated
      compounds were evaluated for their acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) activities. Compound 4 showed the highest inhibitory
      activity towards BChE with an IC50 value of 47.9 MUM. On the other hand, Compound
      5 showed the highest inhibitory activity towards AChE with an IC50 value of 69.1
      MUM.

PMID- 24333261
TI  - Antibacterial prenylbenzoic acid derivatives from Anodendron formicinum.
AB  - A phytochemical investigation on the stems of Anodendron formicinum led to the
      isolation of eight prenylbenzoic acid derivatives. Three of these were new
      compounds, designated as formicinuosides A (1), B (2), and C (3). Their
      structures were elucidated on the basis of extensive spectroscopic analysis, as
      well as by comparison with the reported spectroscopic data. This is the first
      report of chemical constituents from A. formicinum and their antimicrobial
      activities. Among the isolated compounds, compounds 4, 6 and 8 showed significant
      antibacterial activities against Providensia smartii with MIC values of 0.781
      MUg/mL. Moreover, compound 8 showed remarkable antibacterial activity against
      Escherichia coli with MIC value of 0.781 MUg/mL.

PMID- 24333262
TI  - Assembly of human organs from stem cells to study liver disease.
AB  - Recently, significant developments in the field of liver tissue engineering have
      raised new possibilities for the study of complex physiological and
      pathophysiological processes in vitro, as well as the potential to assemble
      entire organs for transplantation. Human-induced pluripotent stem cells have been
      differentiated into relatively functional populations of hepatic cells, and novel
      techniques to generate whole organ acellular three-dimensional scaffolds have
      been developed. In this review, we highlight the most recent advances in organ
      assembly regarding the development of liver tissue in vitro. We emphasize
      applications that involve multiple types of cells with a biomimetic spatial
      organization for which three-dimensional configurations could be used for drug
      development or to explain mechanisms of disease. We also discuss applications of
      liver organotypic surrogates and the challenges of translating the highly
      promising new field of tissue engineering into a proven platform for predicting
      drug metabolism and toxicity. 

PMID- 24333263
TI  - The pneumonectomy model of compensatory lung growth: insights into lung
      regeneration.
AB  - Pneumonectomy (PNX) in experimental animals leads to a species- and age-dependent
      compensatory growth of the remaining lung lobes. PNX mimics the loss of
      functional gas exchange units observed in a number of chronic destructive lung
      diseases. However, unlike in disease models, this tissue loss is well defined,
      reproducible and lacks accompanying inflammation. Furthermore, compensatory
      responses to the tissue loss can be easily quantified. This makes PNX a
      potentially useful model for the study of the cellular and molecular events which
      occur during realveolarisation. It may therefore help to get a better
      understanding of how to manipulate these pathways, in order to promote the
      generation of new alveolar tissue as therapies for destructive lung diseases.
      This review will explore the insights that experimental PNX has provided into the
      physiological factors which promote compensatory lung growth as well as the
      importance of age and species in the rate and extent of compensation. In
      addition, more recent studies which are beginning to uncover the key cellular and
      molecular pathways involved in realveolarisation will be discussed. The potential
      relevance of experimental pneumonectomy to novel therapeutic strategies which aim
      to promote lung regeneration will also be highlighted.

PMID- 24333265
TI  - Improving cardiovascular outcomes in rheumatic diseases: therapeutic potential of
      circulating endothelial progenitor cells.
AB  - Patients with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE)
      have a significantly increased risk of cardiovascular disease (CVD). The reason
      for this is unclear but may be due, at least in part, to the failure of
      endothelial repair mechanisms. Over the last 15 years there has been much
      interest in the mechanisms of endothelial renewal and its potential as a therapy
      for CVD. In the circulation there are two distinct populations of cells; myeloid
      angiogenic cells (MACs) which augment repair by the paracrine secretion of
      angiogenic factors, and outgrowth endothelial cells (OECs) which are true
      endothelial progenitor cells (EPCs) and promote vasculogenesis by differentiating
      into mature endothelium. There are marked abnormalities in the number and
      function of these cells in patients with RA and SLE. Inflammatory cytokines
      including interferon-alpha (IFNalpha) and tumour-necrosis factor alpha (TNFalpha)
      both impair MAC and OEC function ex vivo and may therefore contribute to the CVD
      risk in these patients. Whilst administration of mononuclear cells, MACs and
      other progenitors has improved cardiovascular outcomes in the acute setting, this
      is not a viable option in chronic disease. The pharmacological manipulation of
      MAC/OEC function in vivo however has the potential to significantly improve
      endothelial repair and thus reduce CVD in this high risk population.

PMID- 24333266
TI  - Epigenetic modulation of RFC1, MHC2TA and HLA-DR in systemic lupus erythematosus:
      association with serological markers and six functional polymorphisms of one
      carbon metabolic pathway.
AB  - The current study was conducted to elucidate the effect of genetic variations in
      one-carbon metabolism on the epigenetic regulation of major histocompatibility
      complex II transactivator (MHC2TA), reduced folate carrier 1 (RFC1/SLC19A1) and
      human leukocyte antigen (HLA)-DR in systemic lupus erythematosus (SLE). PCR
      RFLP/AFLP, bisulfite-sequencing and real-time PCR approaches were used for
      genetic, epigenetic and expression analysis respectively. SLE cases exhibited
      elevated plasma homocysteine levels compared to healthy controls (24.93 +/- 1.3
      vs. 11.67 +/- 0.48 MUmol/l), while plasma folate levels showed no association
      (7.10 +/- 2.49 vs. 7.64 +/- 2.09 ng/ml). The RFC1 80G>A polymorphism showed 1.32
      fold risk (95% CI: 1.02-1.72) for SLE, while glutamate carboxypeptidase II
      (GCPII) 1561C>T showed reduced risk (OR: 0.47, 95% CI: 0.24-0.90). The expression
      of RFC1 (0.37 +/- 0.09 vs. 0.60 +/- 0.17) and HLA-DR (0.68 +/- 0.17 vs. 0.98 +/-
      0.02) was down regulated in the SLE cases. The hypermethylation of RFC1 as
      observed in the current study may contribute for its down regulation. Plasma
      folate and thymidylate synthase (TYMS) 5'-UTR 28 bp tandem repeat showed an
      inverse association with methylation of RFC1 and MHC2TA. SLE cases with
      hypocomplementemia showed hypermethylation of RFC1, hypomethylation/up regulation
      of MHC2TA and down regulation of HLA-DR. The hypermethylation of MHC2TA and down
      regulation of RFC1, MHC2TA and HLA-DR were observed in anti-cardiolipin antibody
      positive SLE cases. The up regulation of RFC1 and HLA-DR was observed in anti
      dsDNA antibody positive SLE cases. The hypomethylation/upregulation of RFC1 and
      MHC2TA was observed in anti-RNP antibody positive cases. To conclude, one-carbon
      genetic variants influence epigenetic of MHC2TA and RFC1, thus contributing to
      phenotypic heterogeneity of SLE.

PMID- 24333267
TI  - The association of FOXO3A gene polymorphisms with serum FOXO3A levels and
      oxidative stress markers in vitiligo patients.
AB  - Vitiligo is an acquired epidermal pigment loss of the skin. Oxidative stress is
      one of the major theories in the pathophysiology of vitiligo. FOXO3A is the
      forkhead members of the class O (FOXO) transcription factors, and plays an
      important role in cell cycle regulation, apoptosis, oxidative stress, and DNA
      repair. The aim of our study was to investigate FOXO3A gene polymorphisms and
      FOXO3A protein levels, activities of superoxide dismutase (SOD) and catalase
      antioxidant enzymes in vitiligo patients and healthy controls. Moreover, the
      level of plasma advanced oxidation protein products (AOPP) in subjects was
      evaluated to understand the possible role of protein oxidation in disease
      etiology. Study groups included 82 vitiligo patients and 81 unrelated healthy
      controls. FOXO3A polymorphisms were determined using polymerase chain reaction
      restriction fragment length polymorphism method. FOXO3A levels and catalase
      activity were measured by ELISA whereas AOPP levels and SOD activity was measured
      by spectrophotometric analysis. We found a significant relationship between
      rs4946936 polymorphism of FOXO3A gene and vitiligo/active vitiligo patients
      (p=0.017; p=0.019 respectively), but not for rs2253310 (p>0.05). SOD activity and
      AOPP levels of vitiligo patient were increased compared with control group,
      whereas FOXO3A levels and catalase enzyme activity of vitiligo patient were
      decreased compared with control group (p<0.05). Our study indicates that
      rs4946936 of FOXO3A gene may associate susceptibility of vitiligo, especially
      active vitiligo. Moreover, our results confirm that oxidative stress may play a
      role in the pathophysiology of vitiligo. Further studies with larger samples are
      required to elucidate the role of FOXO3A in vitiligo. 

PMID- 24333268
TI  - Isolation and characterization of a buffalograss (Buchloe dactyloides)
      dehydration responsive element binding transcription factor, BdDREB2.
AB  - Dehydration responsive element binding (DREB) transcription factors play an
      important role in the regulation of stress-related genes. These factors
      contribute to resistance to different abiotic stresses. In the present study, a
      novel DREB transcription factor, BdDREB2, isolated from Buchloe dactyloides, was
      cloned and characterized. The BdDREB2 protein was estimated to have a molecular
      weight of 28.36kDa, a pI of 5.53 and a typical AP2/ERF domain. The expression of
      BdDREB2 was involved in responses to drought and salt stresses. Overexpression of
      BdDREB2 in tobacco showed higher relative water and proline content, and was
      associated with lower MDA content under drought stress, suggesting that the
      transgenic tobacco may tolerate drought stress better. Results demonstrate that
      BdDREB2 may play an important role in the regulation of abiotic stress responses,
      and mediate many physiological pathways that enhance stress tolerance in plants. 

PMID- 24333269
TI  - Bovine and murine tissue expression of insulin like growth factor-I.
AB  - The genomic architecture and expression of the Igf-1 gene are complex yielding
      multiple IGF-I transcript isoforms with putative functional contributions to
      growth and metabolism. Using RNA-seq on different tissues, physiological states,
      and species, the breadth of transcripts expressed was determined. Tissues from
      pre- and post-pubertal heifers and mature mice were collected and the transcript
      isoforms characterized. Three different IGF-I isoforms were detected in heifers
      with Class 1 transcripts most abundantly expressed. The pituitary reduced IGF-I
      expression post-pubertally whereas the uterus increased expression. Murine IGF-I
      transcript expression was more diverse utilizing multiple exons, start sites, and
      3'UTRs. The RNA-seq methodology to characterize expression profiles permits
      assessment of the transcript isoforms yielding insight into functional roles of
      each transcript. 

PMID- 24333271
TI  - Role and importance of polymorphisms with respect to DNA methylation for the
      expression of CYP2E1 enzyme.
AB  - Different individuals possess slightly different genetic information and show
      genetically-determined differences in several enzyme activities due to genetic
      variability. Following an integrated approach, we studied the polymorphisms and
      methylation of sites contained in the 5' flanking region of the metabolizing
      enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic
      liver cell lines, since to date little is known about the influence of these
      (epi)genetic elements in basal conditions and under induction by the specific
      inductor and a demethylating agent. In treated cells, reduced DNA methylation,
      assessed both at genomic and gene level, was not consistently associated with the
      increase of enzyme expression. Interestingly, the Rsa/Pst haplotype
      differentially influenced CYP2E1 enzyme expression. In addition, regarding the
      Variable Number of Tandem Repeats polymorphism, cells with A4/A4 genotype showed
      a greater expression inhibition (ranging from 20% to 30%) compared with others
      carrying the A2/A2 one, while those cells bringing A2/A3 genotype showed an
      increase of expression (of 25%, about). Finally, we demonstrated for the first
      time that the A2 and A3 CYP2E1 alleles play a more important role in the
      expression of the enzyme, compared with other (epi)genetic factors, since they
      are binding sites for trans-acting proteins. 

PMID- 24333270
TI  - Regulation of 3beta-hydroxysteroid dehydrogenase and sulphotransferase 2A1 gene
      expression in primary porcine hepatocytes by selected sex-steroids and plant
      secondary metabolites from chicory (Cichorium intybus L.) and wormwood (Artemisia
      sp.).
AB  - In pigs the endogenously produced compound androstenone is metabolised in the
      liver in two steps by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and
      sulphotransferase 2A1 (SULT2A1). The present study investigated the effect of
      selected sex-steroids (0.01-1 MUM androstenone, testosterone and estradiol),
      skatole (1-100 MUM) and secondary plant metabolites (1-100 MUM) on the expression
      of 3beta-HSD and SULT2A1 mRNA. Additionally the effect of a global methanolic
      extract of dried chicory root was investigated and compared to previous obtained
      in vivo effects. Primary hepatocytes were isolated from the livers of piglets
      (crossbreed: Landrace*Yorkshire and Duroc) and cultured for 24h before treatment
      for an additionally 24h. RNA was isolated from the hepatocytes and specific gene
      expression determined by RT-PCR using TaqMan probes. The investigated sex
      steroids had no effect on the mRNA expression of 3beta-HSD and SULT2A1, while
      skatole decreased the content of SULT2A1 30% compared to control. Of the
      investigated secondary plant metabolites artemisinin and scoparone (found in
      Artemisia sp.) lowered the content of SULT2A1 by 20 and 30% compared to control,
      respectively. Moreover, we tested three secondary plant metabolites (lactucin,
      esculetin and esculin) found in chicory root. Lactucin increased the mRNA content
      of both 3beta-HSD and SULT2A1 by 200% compared to control. An extract of chicory
      root was shown to decrease the expression of both 3beta-HSD and SULT2A1. It is
      concluded that the gene expression of enzymes with importance for androstenone
      metabolism is regulated by secondary plant metabolites in a complex manner.

PMID- 24333272
TI  - Identity confusion of glioma cell lines.

PMID- 24333273
TI  - Metabolic engineering of Phaeodactylum tricornutum for the enhanced accumulation
      of omega-3 long chain polyunsaturated fatty acids.
AB  - We have engineered the diatom Phaeodactylum tricornutum to accumulate the high
      value omega-3 long chain polyunsaturated fatty acid docosahexaenoic acid (DHA).
      This was achieved by the generation of transgenic strains in which the Delta5
      elongase from the picoalga Ostreococcus tauri was expressed to augment the
      endogenous fatty acid biosynthetic pathway. Expression of the heterologous
      elongase resulted in an eight-fold increase in docosahexaenoic acid content,
      representing a marked and valuable change in the fatty acid profile of this
      microalga. Importantly, DHA was shown to accumulate in triacylglycerols, with
      several novel triacylglycerol species being detected in the transgenic strains.
      In a second iteration, co-expression of an acyl-CoA-dependent Delta6-desaturase
      with the Delta5-elongase further increased DHA levels. Together, this
      demonstrates for the first time the potential of using iterative metabolic
      engineering to optimise omega-3 content in algae. 

PMID- 24333264
TI  - Antioxidant gene therapy against neuronal cell death.
AB  - Oxidative stress is a common hallmark of neuronal cell death associated with
      neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as
      well as brain stroke/ischemia and traumatic brain injury. Increased accumulation
      of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated
      in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis
      and accumulation of aggregated proteins observed in neurodegenerative disorders,
      which lead to the activation/modulation of cell death mechanisms that include
      apoptotic, necrotic and autophagic pathways. Thus, the design of novel
      antioxidant strategies to selectively target oxidative stress and redox imbalance
      might represent important therapeutic approaches against neurological disorders.
      This work reviews the evidence demonstrating the ability of genetically encoded
      antioxidant systems to selectively counteract neuronal cell loss in
      neurodegenerative diseases and ischemic brain damage. Because gene therapy
      approaches to treat inherited and acquired disorders offer many unique advantages
      over conventional therapeutic approaches, we discussed basic research/clinical
      evidence and the potential of virus-mediated gene delivery techniques for
      antioxidant gene therapy. 

PMID- 24333274
TI  - Improving D-glucaric acid production from myo-inositol in E. coli by increasing
      MIOX stability and myo-inositol transport.
AB  - D-glucaric acid has been explored for a myriad of potential uses, including
      biopolymer production and cancer treatment. A biosynthetic route to produce D
      glucaric acid from glucose has been constructed in Escherichia coli (Moon et al.,
      2009b), and analysis of the pathway revealed myo-inositol oxygenase (MIOX) to be
      the least active enzyme. To increase pathway productivity, we explored protein
      fusion tags for increased MIOX solubility and directed evolution for increased
      MIOX activity. An N-terminal SUMO fusion to MIOX resulted in a 75% increase in D
      glucaric acid production from myo-inositol. While our directed evolution efforts
      did not yield an improved MIOX variant, our screen isolated a 941 bp DNA fragment
      whose expression led to increased myo-inositol transport and a 65% increase in D
      glucaric acid production from myo-inositol. Overall, we report the production of
      up to 4.85 g/L of D-glucaric acid from 10.8 g/L myo-inositol in recombinant E.
      coli.

PMID- 24333275
TI  - Supplementation with gamma-tocopherol attenuates endotoxin-induced airway
      neutrophil and mucous cell responses in rats.
AB  - Neutrophil-mediated tissue injury is a shared pathogenesis of both chronic
      pulmonary diseases and acute responses to pathogens, allergens, and airborne
      pollutants. Interventions to minimize toxic effects of neutrophil-derived
      oxidants and proteases are usually limited to corticosteroids, which can have
      adverse side effects. We used a rodent model of endotoxin-induced lung injury to
      test the hypothesis that the dietary supplement gamma-tocopherol (gammaT), a
      natural form of vitamin E with antioxidant and novel anti-inflammatory
      properties, will protect from adverse nasal and pulmonary inflammatory responses
      induced by endotoxin (lipopolysaccharide; LPS). Male Fisher F344 rats were
      intranasally (i.n.) instilled with LPS for 2 consecutive days. Beginning 2 days
      before i.n. LPS, the rats were gavaged daily with 30mg/kg gammaT. Twenty-four
      hours after the last i.n. LPS, bronchoalveolar lavage fluid (BALF) was collected,
      and pulmonary and nasal tissues were analyzed for gene expression and
      morphometric analyses of neutrophils and intraepithelial mucosubstances (IM). LPS
      caused increased BALF total cells (70% increase), neutrophils (300%), protein
      (35%), PGE2 (500%), and secreted mucins (75%). Robust increases in neutrophils
      and IM were detected in conducting airways. Pulmonary expression of MUC5AC, MIP
      2, CINC-1, and MCP-1 was elevated three- to eightfold by LPS. Treatment with
      gammaT inhibited LPS-induced increases in BALF total cells, neutrophils, protein,
      PGE2, and secreted mucins, as well as IM and tissue neutrophil influx.
      Furthermore gammaT induced the expression of the regulatory cytokines IL-10 and
      IFN-gamma while decreasing MUC5AC, MIP-2, CINC-1, and MCP-1. These data
      demonstrate novel therapeutic effects of the dietary vitamin E gammaT promoting
      anti-inflammatory pathways to protect from neutrophil-mediated lung injury. 

PMID- 24333277
TI  - Chlorella modulates insulin signaling pathway and prevents high-fat diet-induced
      insulin resistance in mice.
AB  - AIMS: The search for natural agents that minimize obesity-associated disorders is
      receiving special attention. In this regard, the present study aimed to evaluate
      the prophylactic effect of Chlorella vulgaris (CV) on body weight, lipid profile,
      blood glucose and insulin signaling in liver, skeletal muscle and adipose tissue
      of diet-induced obese mice. MAIN METHODS: Balb/C mice were fed either with
      standard rodent chow diet or high-fat diet (HFD) and received concomitant
      treatment with CV for 12 consecutive weeks. Triglyceride, free fatty acid, total
      cholesterol and fractions of cholesterol were measured using commercial assay.
      Insulin and leptin levels were determined by enzyme-linked immunosorbent assay
      (ELISA). Insulin and glucose tolerance tests were performed. The expression and
      phosphorylation of IRbeta, IRS-1 and Akt were determined by Western blot
      analyses. KEY FINDINGS: Herein we demonstrate for the first time in the
      literature that prevention by CV of high-fat diet-induced insulin resistance in
      obese mice, as shown by increased glucose and insulin tolerance, is in part due
      to the improvement in the insulin signaling pathway at its main target tissues,
      by increasing the phosphorylation levels of proteins such as IR, IRS-1 and Akt.
      In parallel, the lower phosphorylation levels of IRS-1(ser307) were observed in
      obese mice. We also found that CV administration prevents high-fat diet-induced
      dyslipidemia by reducing triglyceride, cholesterol and free fatty acid levels.
      SIGNIFICANCE: We propose that the modulatory effect of CV treatment preventing
      the deleterious effects induced by high-fat diet is a good indicator for its use
      as a prophylactic-therapeutic agent against obesity-related complications.

PMID- 24333276
TI  - Proteomic identification and quantification of S-glutathionylation in mouse
      macrophages using resin-assisted enrichment and isobaric labeling.
AB  - S-Glutathionylation (SSG) is an important regulatory posttranslational
      modification on protein cysteine (Cys) thiols, yet the role of specific cysteine
      residues as targets of modification is poorly understood. We report a novel
      quantitative mass spectrometry (MS)-based proteomic method for site-specific
      identification and quantification of S-glutathionylation across different
      conditions. Briefly, this approach consists of initial blocking of free thiols by
      alkylation, selective reduction of glutathionylated thiols, and covalent capture
      of reduced thiols using thiol affinity resins, followed by on-resin tryptic
      digestion and isobaric labeling with iTRAQ (isobaric tags for relative and
      absolute quantitation) for MS-based identification and quantification. The
      overall approach was initially validated by application to RAW 264.7 mouse
      macrophages treated with different doses of diamide to induce glutathionylation.
      A total of 1071 Cys sites from 690 proteins were identified in response to
      diamide treatment, with ~90% of the sites displaying >2-fold increases in SSG
      modification compared to controls. This approach was extended to identify
      potential SSG-modified Cys sites in response to H2O2, an endogenous oxidant
      produced by activated macrophages and many pathophysiological stimuli. The
      results revealed 364 Cys sites from 265 proteins that were sensitive to S
      glutathionylation in response to H2O2 treatment, thus providing a database of
      proteins and Cys sites susceptible to this modification under oxidative stress.
      Functional analysis revealed that the most significantly enriched molecular
      function categories for proteins sensitive to SSG modifications were free radical
      scavenging and cell death/survival. Overall the results demonstrate that our
      approach is effective for site-specific identification and quantification of SSG
      modified proteins. The analytical strategy also provides a unique approach to
      determining the major pathways and cellular processes most susceptible to S
      glutathionylation under stress conditions. 

PMID- 24333278
TI  - Assay methods for small ubiquitin-like modifier (SUMO)-SUMO-interacting motif
      (SIM) interactions in vivo and in vitro using a split-luciferase complementation
      system.
AB  - SUMOylation is a posttranslational process that attaches a small ubiquitin-like
      modifier (SUMO) to its target proteins covalently. SUMOylation controls multiple
      cellular processes through the recognition of SUMO by a SUMO-interacting motif
      (SIM). In this study, we developed assay systems for detecting noncovalent
      interactions between SUMO and SIM in cells using split-luciferase
      complementation. We applied a version of this assay to the detection of in vitro
      SUMO-SIM interactions using a bacterial expression system. These novel assays
      enable screening of inhibitors of SUMO-dependent protein-protein interactions,
      either in vivo or in vitro, in a high-throughput manner. 

PMID- 24333279
TI  - Information extraction during simultaneous motion processing.
AB  - When confronted with multiple moving objects the visual system can process them
      in two stages: an initial stage in which a limited number of signals are
      processed in parallel (i.e. simultaneously) followed by a sequential stage. We
      previously demonstrated that during the simultaneous stage, observers could
      discriminate between presentations containing up to 5 vs. 6 spatially localized
      motion signals (Edwards & Rideaux, 2013). Here we investigate what information is
      actually extracted during the simultaneous stage and whether the simultaneous
      limit varies with the detail of information extracted. This was achieved by
      measuring the ability of observers to extract varied information from low detail,
      i.e. the number of signals presented, to high detail, i.e. the actual directions
      present and the direction of a specific element, during the simultaneous stage.
      The results indicate that the resolution of simultaneous processing varies as a
      function of the information which is extracted, i.e. as the information
      extraction becomes more detailed, from the number of moving elements to the
      direction of a specific element, the capacity to process multiple signals is
      reduced. Thus, when assigning a capacity to simultaneous motion processing, this
      must be qualified by designating the degree of information extraction. 

PMID- 24333280
TI  - Analysis of microsaccades and pupil dilation reveals a common decisional origin
      during visual search.
AB  - During free viewing visual search, observers often refixate the same locations
      several times before and after target detection is reported with a button press.
      We analyzed the rate of microsaccades in the sequence of refixations made during
      visual search and found two important components. One related to the visual
      content of the region being fixated; fixations on targets generate more
      microsaccades and more microsaccades are generated for those targets that are
      more difficult to disambiguate. The other empathizes non-visual decisional
      processes; fixations containing the button press generate more microsaccades than
      those made on the same target but without the button press. Pupil dilation during
      the same refixations reveals a similar modulation. We inferred that generic
      sympathetic arousal mechanisms are part of the articulated complex of perceptual
      processes governing fixational eye movements. 

PMID- 24333281
TI  - Pacing-induced torsades de pointes after the short-long-short sequence in a
      patient with a biventricular defibrillator: what is the mechanism?

PMID- 24333282
TI  - Response or nonresponse to cardiac resynchronization therapy in heart failure:
      lessons from the real world.

PMID- 24333284
TI  - Multipoint pacing: can we connect the dots to improve resynchronization therapy?

PMID- 24333283
TI  - Patients treated with catheter ablation for ventricular tachycardia after an ICD
      shock have lower long-term rates of death and heart failure hospitalization than
      do patients treated with medical management only.
AB  - BACKGROUND: Ventricular arrhythmias in patients with implantable cardioverter
      defibrillators (ICDs) adversely affect outcomes. Antiarrhythmic approaches to
      ventricular tachycardia (VT) have variable efficacy and may increase risk of
      ventricular arrhythmias, worsening cardiomyopathy, and death. Comparatively, VT
      ablation is an alternative approach that may favorably affect outcomes.
      OBJECTIVE: To further explore the effect on long-term outcomes after catheter
      ablation of VT, we compared patients with history of ICD shocks who did not
      undergo ablation, patients with a history of ICD shocks that underwent ablation,
      and patients with ICDs who had no history of ICD shocks. METHODS: A total of 102
      consecutive patients with structural heart disease who underwent VT ablation for
      recurrent ICD shocks were compared with 2088 patients with ICDs and no history of
      appropriate shocks and 817 patients with ICDs and a history of appropriate shocks
      for VT or ventricular fibrillation. Outcomes considered were mortality, heart
      failure hospitalization, atrial fibrillation, and stroke/transient ischemic
      attack. RESULTS: The mean age of 3007 patients was 65.4 +/- 13.9 years. Over long
      term follow-up, 866 (28.8%) died, 681 (22.7%) had a heart failure admission, 706
      (23.5%) developed new-onset atrial fibrillation, and 224 (7.5%) had a stroke. The
      multivariate-adjusted risks of deaths and heart failure hospitalizations were
      higher in patients with history of ICD shocks who were treated medically than in
      patients with ICDs and no history of shock (hazard ratio [HR] 1.45; P < .0001 vs
      HR 2.00; P < .0001, respectively). The multivariate-adjusted risks were
      attenuated after VT ablation with death and heart failure hospitalization rates
      similar to those of patients with no shock (HR 0.89; P = .58 vs HR 1.38; P = .09,
      respectively). A similar nonsignificant trend was seen with stroke/transient
      ischemic attack. CONCLUSIONS: Patients treated with VT ablation after an ICD
      shock have a significantly lower risk of death and heart failure hospitalization
      than did patients managed medically only. The adverse event rates after VT
      ablation were similar to those of patients with ICDs but without VT.

PMID- 24333285
TI  - Fetal arrhythmias associated with cardiac rhabdomyomas.
AB  - BACKGROUND: Primary heart tumors in fetuses are rare and mainly represent
      rhabdomyomas. The tumors have a variable expression and can be associated with
      arrhythmias, including both wide and narrow QRS tachycardia. Although multiple
      Doppler techniques exist to assess fetal heart rhythm, it can be difficult to
      record precise electrophysiological abnormalities in fetal life. OBJECTIVE:
      Investigations defining precise electrophysiological diagnosis were performed by
      using fetal magnetocardiography (fMCG). METHODS: In addition to routine fetal
      echocardiography, fMCG was used to investigate electrophysiological rhythm
      patterns in a series of 10 fetuses with cardiac rhabdomyomas. RESULTS: The mean
      gestational age of the fetuses was 28.6 +/- 4.7 weeks. The multiple rhabdomyomas
      were mainly located in the right and left ventricles as well as around the
      atrioventricular groove. Arrhythmias or conduction abnormalities were diagnosed
      in all 10 patients, although only 6 of them were referred due to that indication.
      Remarkably, 80% (8 of 10) had associated Wolff-Parkinson-White pre-excitation. In
      addition, we found prominent P waves in 4 fetuses. CONCLUSION: In fetuses with
      rhabdomyomas, a disease where rhythm pathology is common, precise
      electrophysiological diagnosis can now be made by fMCG. fMCG is complimentary to
      echocardiography for rhythm assessment and can detect conduction abnormalities
      that are not possible to diagnose prenatally with M-mode or pulsed Doppler
      ultrasound. Risk factor assessment using fMCG can support pregnancy management
      and postnatal treatment and follow-up.

PMID- 24333286
TI  - Visualization of the left atrial appendage from the coronary sinus by
      intracardiac echocardiography.

PMID- 24333287
TI  - Right ventricular apical pacing-induced left ventricular dyssynchrony is
      associated with a subsequent decline in ejection fraction.
AB  - BACKGROUND: In patients with normal left ventricular (LV) ejection fraction (EF),
      the interposition of chronic, high-dose right ventricular apical (RVA) pacing may
      produce late EF decline. OBJECTIVE: To test the hypothesis that LV dyssynchrony,
      defined echocardiographically and apparent early after interposition of pacing,
      would be greater in patients who subsequently demonstrated EF decline. METHODS:
      Ninety-one patients with normal prepacing EF who underwent atrioventricular node
      ablation and subsequent high-dose RVA pacing were studied. Transthoracic
      echocardiograms were performed early (median 4 months) and late (median 28
      months) after interposition of pacing, with a significant decline in EF between
      these studies defined as >=5%. Speckle-tracking longitudinal strain analysis of
      the early echocardiogram was performed to quantify dyssynchrony. In addition to
      standard dyssynchrony indices, a novel index of apex-to-base mechanical
      propagation delay (MPD) was used. RESULTS: Multivariable analysis determined that
      MPD of the septum correlated with a significant decline in EF, independent of all
      other dyssynchrony, clinical, or pacing variables. A septal MPD value exceeding
      50 ms was associated with EF decline at 81% sensitivity and 88% specificity.
      CONCLUSIONS: Dyssynchrony, in particular septal MPD, measured early after
      interposition of high-dose RVA pacing predicted a significant late decline in EF
      in patients who had normal prepacing EF.

PMID- 24333288
TI  - Intact neural system of the portal vein is important for maintaining normal
      glucose metabolism by regulating glucagon-like peptide-1 and insulin sensitivity.
AB  - The portal neural system may have an important role on the regulation of glucose
      homeostasis since activation of the gut-brain-liver neurocircuit by nutrient
      sensing in the proximal intestine reduces hepatic glucose production through
      enhanced liver insulin sensitivity. Although there have been many studies
      investigating the role of portal neural system, surgical denervation of the sole
      portal vein has not been reported to date. The aim of this study was to clarify
      the role of the portal neural system on the regulation of glucose homeostasis and
      food intake in the physiological condition. Surgical denervation of portal vein
      (DV) was performed in 10 male 12 week-old Wistar rats. The control was a sham
      operation (SO). One week after surgery, food intake and body weight were
      monitored; an oral glucose tolerance test (OGTT) was performed; and glucagon-like
      peptide-1 (GLP-1) and insulin levels during OGTT were assayed. In addition,
      insulinogenic index, homeostatic model assessment, and Matsuda index were
      calculated. All rats regained the preoperative body weight at one week after
      surgery. There was no significant difference in food intake between DV and SO
      rats. DV rats exhibited increased blood glucose levels associated with decreased
      insulin sensitivity but increased GLP-1 and insulin secretion during OGTT. In
      summary, in the physiological state, loss of the portal neural system leads to
      decreased insulin sensitivity and increased blood glucose levels but does not
      affect food intake. These data indicate that an intact portal neural system is
      important for maintaining normal glucose metabolism. 

PMID- 24333290
TI  - Influence of paroxysmal activity on background synchronization in epileptic
      recordings.
AB  - BACKGROUND: The presence of spikes and sharp waves in recordings of epileptic
      patients contaminates background signal synchronization. When estimating
      functional connectivity between extended cortical areas, the influence of
      epileptic spikes in specific areas should be considered; however, this step is
      sometimes overlooked. We present a simple method for quantifying the influence of
      epileptic activity on background signal synchronization. METHOD: Standard
      synchronization measures were calculated for both pure correlated Gaussian
      signals and correlated Gaussian signals with different levels of epileptic spikes
      in order to determine the influence of epileptic activity on synchronization
      estimates. RESULTS: Synchronization from invasive epileptic recordings (e.g.,
      depth electrodes) displays a much higher bias due to epileptic activity than
      superficial electrodes. Moreover, statistical methods such as mutual information
      are more affected by spike presence than phase synchronization methods. The
      influence of spikes is far greater at low values of background synchronization.
      CONCLUSIONS: The information provided by this procedure makes it possible to
      differentiate true background synchronization from spike synchronization. Thus,
      our procedure serves as a guide for analyzing synchronization and functional
      connectivity calculations in epileptic recordings.

PMID- 24333289
TI  - A cellular model of amyloid precursor protein processing and amyloid-beta peptide
      production.
AB  - BACKGROUND: A hallmark pathologic feature of Alzheimer's disease (AD) is
      accumulation of neuritic senile plaques in the brain parenchyma. Neurotoxic
      plaque cores are composed predominantly of amyloid-beta (Abeta) peptides of 40
      and 42 amino acids in length, formed by sequential cleavage of amyloid precursor
      protein (APP) by beta-, and gamma-secretases. There is a great interest in
      approaches to modulate Abeta peptide production and develop therapeutic
      interventions to reduce Abeta levels to halt or slow the progression of
      neurodegeneration. NEW METHOD: We characterized and present the BE(2)-M17 human
      neuroblastoma cell line as a novel in vitro model of the APP-cleavage cascade to
      support future (1) functional studies of molecular regulators in Abeta
      production, and (2) high-throughput screening assays of new pharmacotherapeutics.
      RESULTS: In BE(2)-M17 cells, both RNA (i.e., RT-PCR, RNA sequencing) and protein
      analyses (i.e., Western blots, ELISA), show endogenous expression of critical
      components of the amyloidogenic pathway, APP-cleavage intermediates CTF83 and
      CTF99, and final cleavage products Abeta40 and Abeta42. We further report effects
      of retinoic acid-mediated differentiation on morphology and gene expression in
      this cell line. COMPARISON WITH EXISTING METHOD(S): In contrast to primary
      isolates or other cell lines reported in current literature, BE(2)-M17 not only
      sustains baseline expression of the full contingent of APP-processing components,
      but also remains stably adherent during culture, facilitating experimental
      manipulations. CONCLUSIONS: Our evidence supports the use of BE(2)-M17 as a
      novel, human, cell-based model of the APP processing pathway that offers a
      potential streamlined approach to dissect molecular functions of endogenous
      regulatory pathways, and perform mechanistic studies to identify modulators of
      Abeta production.

PMID- 24333291
TI  - Metabolic and histopathological profile of Rattus norvegicus (Wistar)
      experimentally infected by Angiostrongylus cantonensis (Chen, 1935).
AB  - Eosinophilic meningitis is a disease characterized by increased eosinophils in
      the cerebrospinal fluid (CSF), which is the most commonly caused by invasion of
      the central nervous system by helminths, as occurs in Angiostrongylus cantonensis
      infections. The rodent Rattus norvegicus is the definitive natural host and
      humans act as accidental hosts and can become infected by eating raw or
      undercooked snails or food contaminated with infective L3 larvae. Recently in
      Brazil there have been four cases of eosinophilic meningitis due to ingestion of
      infected Achatina fulica. To evaluate biochemical and histopathological changes
      caused by this parasite, R. norvegicus were experimentally infected with 100 L3
      larvae of A. cantonensis. After the anesthetic procedure, serum from the rodents
      was collected from the inferior vena cava for evaluation of the levels of
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
      phosphatase (ALKP), gamma-glutamyl transferase (GGT), total protein and its
      fractions. During the necropsy, the liver was collected and weighed. Then a 1-g
      fragment was extracted from the major lobe to quantify the hepatic glycogen and
      fragment remainder was taken from the same lobe and fixed in Milloning's formalin
      for histopathological examination. Additionally, helminths were collected from
      the brain and lungs of the rodents. The activities of AST, ALT, ALKP and GGT in
      the serum and hepatic glycogen increased in response to infection, while the
      levels of globulin and total protein increased only in the eighth week of
      infection and there was a reduction in the levels of serum glucose. Albumin and
      bilirubin concentrations remained stable during the experiment. Infection with A.
      cantonensis caused metabolic and histopathological changes in the rodents. This
      study can contribute to a better understanding of the relationship between A.
      cantonensis and R. norvegicus. 

PMID- 24333292
TI  - Lateral trunk lean gait modification increases the energy cost of treadmill
      walking in those with knee osteoarthritis.
AB  - OBJECTIVE: To compare the energy expenditure of increased lateral trunk lean
      walking - a suggested method of reducing medial compartment knee joint load -
      compared to normal walking in a population of older adults with medial knee
      osteoarthritis (OA). METHOD: Participants completed two randomly-presented
      treadmill walking conditions: 15 min of normal walking or walking with ten
      degrees of peak lateral trunk lean. Lateral trunk lean angle was displayed in
      front of the participant in real-time during treadmill conditions. Energy
      expenditure (VO2 and METs), heart rate (HR), peak lateral trunk lean angle, knee
      pain and perceived exertion were measured and differences between conditions were
      compared using paired t-tests. RESULTS: Twelve participants (five males, mean
      (standard deviation (SD)) age 64.1 (9.4) years, body mass index (BMI) 28.3 (4.9)
      kg/m2) participated. All measures were significantly elevated in the lateral
      trunk lean condition (P < 0.008), except for knee pain (P = 0.22). Oxygen
      consumption (VO2) was, on average 9.5% (95% CI 4.2-14.7%) higher, and HR was on
      average 5.3 beats per minute (95% CI 1.7-9.0 bpm) higher during increased lateral
      trunk lean walking. CONCLUSION: Increased lateral trunk lean walking on a
      treadmill resulted in significantly higher levels of steady-state energy
      expenditure, HR, and perceived exertion, but no difference in knee pain. While
      increased lateral trunk lean has been shown to reduce biomechanical measures of
      joint loading relevant to OA progression, it should be prescribed with caution
      given the potential increase in energy expenditure experienced when it is
      employed.

PMID- 24333294
TI  - O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the
      cartilage of patients with knee osteoarthritis.
AB  - OBJECTIVE: There is increasing evidence that the addition of O-linked N
      acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell
      signaling pathways. In chondrocytes, accumulation of O-GlcNAc-modified proteins
      induces hypertrophic differentiation. Osteoarthritis (OA) is characterized by
      cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes.
      However, the mechanisms responsible for these changes have not been described.
      Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this
      modification are dysregulated in the cartilage of patients with knee OA and
      whether interleukin-1 could induce these modifications in cultured human OA
      chondrocytes (HOC). DESIGN: Human cartilage was obtained from patients with knee
      OA and from age and sex-matched healthy donors. HOC were cultured and stimulated
      with the catabolic cytokine IL-1alpha. Global protein O-GlcNAcylation and the
      synthesis of the key enzymes responsible for this modification, O-GlcNAc
      transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. RESULTS:
      OA was associated with a 4-fold increase in the global O-GlcNAcylation in the
      cartilage. OA cartilage showed a re-distribution of the OGT and OGA isoforms,
      with a net increase in the presence of both enzymes, in comparison to healthy
      cartilage. In HOC, IL-1alpha stimulation rapidly increased O-GlcNAcylation and
      OGT and OGA synthesis. CONCLUSIONS: Our results indicate that a proinflammatory
      milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage,
      together with the dysregulation of the enzymes responsible for this modification.
      The increase in O-GlcNAcylation could be responsible, at least partially, for the
      re-expression of hypertrophic differentiation markers that have been observed in
      OA.

PMID- 24333293
TI  - TSG-6 activity as a novel biomarker of progression in knee osteoarthritis.
AB  - OBJECTIVE: To establish whether there is an association between TSG-6 activity
      and osteoarthritis progression. DESIGN: TSG-6 activity was determined in 132
      synovial fluids from patients with OA of the knee, using a novel quantitative TSG
      6 activity assay. The association between TSG-6 activities at baseline and four
      distinct disease progression states, determined at 3-year follow-up, was analyzed
      using logistic regression. RESULTS: There was a statistically significant
      relationship between TSG-6 activity at baseline and all OA progression states
      over a 3-year period. Patient knees with TSG-6 activities in the top tenth
      percentile, compared to the median activity, had an odds ratio (OR) of at least
      7.86 (confidence interval (CI) [3.2, 20.5]) for total knee arthroplasty (TKA)
      within 3 years, and of at least 5.20 (CI [1.8, 13.9]) after adjustment for
      confounding factors. Receiver operating characteristic (ROC) analysis for knee
      arthroplasty yielded a cut-off point of 13.3 TSG-6 activity units/ml with the
      following parameters: area under the curve 0.90 (CI [0.804, 0.996]), sensitivity
      0.91 (CI [0.59, 0.99]), specificity 0.82 (CI [0.74, 0.88]) and a negative
      predictive value (NPV) of 0.99 (CI [0.934, 0.994]). CONCLUSION: The TSG-6
      activity is a promising independent biomarker for OA progression. Given the high
      NPV, this assay may be particularly suitable for identifying patients at low risk
      of rapid disease progression and to assist in the timing of arthroplasty.

PMID- 24333295
TI  - The role of fat mass and skeletal muscle mass in knee osteoarthritis is different
      for men and women: the NEO study.
AB  - OBJECTIVE: To investigate if the amount of fat mass (FM) or skeletal muscle mass
      (SMM) is more strongly associated with knee osteoarthritis (OA), in both men and
      women. METHODS: The Netherlands Epidemiology of Obesity (NEO) study is a
      population-based cohort aged 45-65 years, including 5313 participants (53%
      female, median body mass index (BMI) 29.9 kg/m(2)). FM (kg), fat percentage, SMM
      (kg) and skeletal muscle (SM) percentage were estimated using bioelectrical
      impedance analysis (BIA). Clinical OA was defined following the ACR criteria.
      Structural OA was defined based on magnetic resonance imaging (MRI) in 1142
      participants. Logistic regression analyses were used to examine the associations
      of all body composition measures with clinical and structural knee OA per
      standard deviation (SD), stratified by sex and adjusted for age and height.
      RESULTS: Clinical or structural OA was present in 25% and 14% of women and 12%
      and 13% of men, respectively. FM and fat percentage were positively associated
      with clinical knee OA in men and women. SMM was positively associated, while the
      SM percentage was negatively associated with clinical OA in both men and women.
      The FM/SMM ratio was positively associated with clinical OA. All determinants
      showed even stronger ORs for structural knee OA. In men, SMM was more strongly
      associated with knee OA as compared to FM whereas in women, FM was most strongly
      associated. CONCLUSION: Especially a high FM/SMM ratio seems to be unfavorable in
      knee OA. In men, SMM is most strongly associated with knee OA whereas in women FM
      seems to be of most importance.

PMID- 24333296
TI  - Avoidance of activity and limitations in activities in patients with
      osteoarthritis of the hip or knee: a 5 year follow-up study on the mediating role
      of reduced muscle strength.
AB  - OBJECTIVE: To evaluate the mediating role of reduced muscle strength in the
      relationship between avoidance of activity and limitations in activities in
      patients with knee or hip osteoarthritis (OA). METHODS: A longitudinal cohort
      study with 5 years follow-up was conducted. Patients with knee or hip OA (n =
      288) were recruited at rehabilitation centers and hospitals. Self-reported and
      performance based limitations in activities, avoidance of activity and muscle
      strength were assessed at baseline, 1, 2, 3 and 5 years follow-up. Generalized
      Estimating Equations (GEE) analyses were used to evaluate mediation. RESULTS: In
      patients with knee OA, reduced knee extensor muscle strength mediated the
      relationship between avoidance of activity and limitations in activities. In
      patients with hip OA reduced hip abductor muscle strength mediates the
      relationship between avoidance of activity and limitations in activities.
      CONCLUSION: The results of this longitudinal study support the theory that
      avoidance of activity leads to deterioration of muscle strength and consequently
      to more limitations in activities in patients with knee and hip OA.

PMID- 24333297
TI  - Depletion of gangliosides enhances cartilage degradation in mice.
AB  - OBJECTIVE: Glycosphingolipids (GSLs) are ubiquitous membrane components that play
      a functional role in maintaining chondrocyte homeostasis. We investigated the
      potential role of gangliosides, one of the major components of GSLs, in
      osteoarthritis (OA) pathogenesis. DESIGN: Both age-associated and instability
      induced OA models were generated using GM3 synthase knockout (GM3S(-/-)) mice. A
      cartilage degradation model and transiently GM3S-transfected chondrocytes were
      analyzed to evaluate the function of gangliosides in OA development. The amount
      of each series of GSLs in chondrocytes after IL-1alpha stimulation was profiled
      using mass spectrometry (MS). RESULTS: OA changes in GM3S(-/-) mice were
      dramatically enhanced with aging compared to those in wild-type (WT) mice. GM3S(
      /-) mice showed more severe instability-induced pathologic OA in vivo.
      Ganglioside deficiency also led to the induction of matrix metalloproteinase
      (MMP)-13 and ADAMTS-5 secretion and chondrocyte apoptosis in vitro. In contrast,
      transient GM3S transfection of chondrocytes suppressed MMP-13 and ADAMTS-5
      expression after interleukin (IL)-1alpha stimulation. GSL profiling revealed the
      presence of abundant gangliosides in chondrocytes after IL-1alpha stimulation.
      CONCLUSION: Gangliosides play a critical role in OA pathogenesis by regulating
      the expression of MMP-13 and ADAMTS-5 and chondrocyte apoptosis. Based on the
      obtained results, we propose that gangliosides are potential target molecules for
      the development of novel OA treatments.

PMID- 24333298
TI  - Anthropogenic noise affects vocal interactions.
AB  - Animal communication plays a crucial role in many species, and it involves a
      sender producing a signal and a receiver responding to that signal. The shape of
      a signal is determined by selection pressures acting upon it. One factor that
      exerts selection on acoustic signals is the acoustic environment through which
      the signal is transmitted. Recent experimental studies clearly show that senders
      adjust their signals in response to increased levels of anthropogenic noise.
      However, to understand how noise affects the whole process of communication, it
      is vital to know how noise affects the receiver's response during vocal
      interactions. Therefore, we experimentally manipulated ambient noise levels to
      expose male European robins (Erithacus rubecula) to two playback treatments
      consisting of the same song: one with noise and another one without noise. We
      found that males responding to a conspecific in a noise polluted environment
      increased minimum frequency and decreased song complexity and song duration.
      Thus, we show that the whole process of communication is affected by noise, not
      just the behaviour of the sender. 

PMID- 24333300
TI  - The structure of the CD3zetazeta transmembrane dimer in lipid bilayers.
AB  - Virtually every aspect of the human adaptive immune response is controlled by T
      cells. The T cell receptor (TCR) complex is responsible for the recognition of
      foreign peptide sequences, forming the initial step in the elimination of germ
      infected cells. The recognition leads to an extracellular conformational change
      that is transmitted intracellularly through the Cluster of Differentiation 3
      (CD3) subunits of the TCR-CD3 complex. Here we address the interplay between the
      disulfide-linked CD3zetazeta dimer, an essential signaling component of the TCR
      CD3 complex, and its lipidic environment. The disulfide bond formation requires
      the absolute presence of a nearby conserved aspartic acid, a fact that has
      mystified the scientific community. We use atomistic simulation methods to
      demonstrate that the conserved aspartic acid pair of the CD3zetazeta dimer leads
      to a deformation of the membrane. This deformation changes the local environment
      of the cysteines and promotes disulfide bond formation. We also investigate the
      role of a conserved Tyr, highlighting its possible role in the interaction with
      other transmembrane components of the TCR-CD3 complex. 

PMID- 24333299
TI  - Trafficking mechanisms of extracellular matrix macromolecules: insights from
      vertebrate development and human diseases.
AB  - Cellular life depends on protein transport and membrane traffic. In multicellular
      organisms, membrane traffic is required for extracellular matrix deposition, cell
      adhesion, growth factor release, and receptor signaling, which are collectively
      required to integrate the development and physiology of tissues and organs.
      Understanding the regulatory mechanisms that govern cargo and membrane flow
      presents a prime challenge in cell biology. Extracellular matrix (ECM) secretion
      remains poorly understood, although given its essential roles in the regulation
      of cell migration, differentiation, and survival, ECM secretion mechanisms are
      likely to be tightly controlled. Recent studies in vertebrate model systems, from
      fishes to mammals and in human patients, have revealed complex and diverse loss
      of-function phenotypes associated with mutations in components of the secretory
      machinery. A broad spectrum of diseases from skeletal and cardiovascular to
      neurological deficits have been linked to ECM trafficking. These discoveries have
      directly challenged the prevailing view of secretion as an essential but
      monolithic process. Here, we will discuss the latest findings on mechanisms of
      ECM trafficking in vertebrates. 

PMID- 24333301
TI  - Connexin 26 null mice exhibit spiral ganglion degeneration that can be blocked by
      BDNF gene therapy.
AB  - Mutations in the connexin 26 gene (GJB2) are the most common genetic cause of
      deafness, leading to congenital bilateral non-syndromic sensorineural hearing
      loss. Here we report the generation of a mouse model for a connexin 26 (Cx26)
      mutation, in which cre-Sox10 drives excision of the Cx26 gene from non-sensory
      cells flanking the auditory epithelium. We determined that these conditional
      knockout mice, designated Gjb2-CKO, have a severe hearing loss.
      Immunocytochemistry of the auditory epithelium confirmed absence of Cx26 in the
      non-sensory cells. Histology of the organ of Corti and the spiral ganglion
      neurons (SGNs) performed at ages 1, 3, or 6 months revealed that in Gjb2-CKO
      mice, the organ of Corti began to degenerate in the basal cochlear turn at an
      early stage, and the degeneration rapidly spread to the apex. In addition, the
      density of SGNs in Rosenthal's canal decreased rapidly along a gradient from the
      base of the cochlea to the apex, where some SGNs survived until at least 6 months
      of age. Surviving neurons often clustered together and formed clumps of cells in
      the canal. We then assessed the influence of brain derived neurotrophic factor
      (BDNF) gene therapy on the SGNs of Gjb2-CKO mice by inoculating Adenovirus with
      the BDNF gene insert (Ad.BDNF) into the base of the cochlea via the scala tympani
      or scala media. We determined that over-expression of BDNF beginning around 1
      month of age resulted in a significant rescue of neurons in Rosenthal's canal of
      the cochlear basal turn but not in the middle or apical portions. This data may
      be used to design therapies for enhancing the SGN physiological status in all
      GJB2 patients and especially in a sub-group of GJB2 patients where the hearing
      loss progresses due to ongoing degeneration of the auditory nerve, thereby
      improving the outcome of cochlear implant therapy in these ears. 

PMID- 24333302
TI  - Clinical use and the Italian demand for activated prothrombin complex and
      activated recombinant factor VII concentrates.

PMID- 24333303
TI  - Public expenditure for plasma-derived and recombinant medicinal products in
      Italy.
AB  - BACKGROUND: In Italy, the supply of plasma-derived medicinal products funded by
      the National Health Service can be through public healthcare facilities,
      accredited pharmacies or toll fractionation agreements between Regions and the
      manufacturer. Pharmaceutical public expenditure includes the supply related to
      the first two channels and costs can significantly vary because of channel
      specific price reductions. This paper describes 2011 public expenditure for
      plasma-derived medicinal products purchased on the market, as well as the cost
      analysis per active substance. MATERIALS AND METHODS: Analysis of the usage of
      plasma-derived medicinal products and of the related expenditure in public
      facilities has been carried out using medicinal product traceability data. The
      analysis related to the accredited pharmacies channel has been carried out using
      quantities for every medicinal package recorded by Pharmacy Associations and
      applying reference prices in force on March 1(st), 2012 as well as discounts for
      the accredited pharmaceutical expenditure imposed by law. RESULTS: At national
      and regional level, total and total per capita expenditures on plasma-derived
      medicinal products by market channel and funded by the National Health Service
      are shown. Analysis was conducted considering the active substances in three
      groups: substances included in toll fractionation agreements, recombinant
      coagulation factors, and other substances not included in toll fractionation
      agreements. In 2011, the national expenditure estimate for plasma-derived and
      recombinant medicinal product acquisition on the market was about ? 535 million.
      DISCUSSION: The purchased volumes and mean purchased prices per unit of each
      substance have a significant influence on the observed regional variability of
      the pharmaceutical public expenditure. A strategy of regional comparison aimed at
      both sharing a national range of reference for purchase prices and evaluating
      modalities for centralised purchasing is desirable.

PMID- 24333304
TI  - Plasma and plasma-derived medicinal product self-sufficiency: the Italian case.

PMID- 24333305
TI  - Plasma-derived medicinal products in Italy: information sources and flows.

PMID- 24333306
TI  - Plasma-derived medicinal products self-sufficiency from national plasma: to what
      extent?

PMID- 24333307
TI  - Sustainability of a public system for plasma collection, contract fractionation
      and plasma-derived medicinal product manufacturing.
AB  - BACKGROUND: In Italy, the financial reimbursement for labile blood components
      exchanged between Regions is regulated by national tariffs defined in 1991 and
      updated in 1993-2003. Over the last five years, the need for establishing
      standard costs of healthcare services has arisen critically. In this perspective,
      the present study is aimed at defining both the costs of production of blood
      components and the related prices, as well as the prices of plasma-derived
      medicinal products obtained by national plasma, to be used for interregional
      financial reimbursement. MATERIALS AND METHODS: In order to analyse the costs of
      production of blood components, 12 out 318 blood establishments were selected in
      8 Italian Regions. For each step of the production process, driving costs were
      identified and production costs were. To define the costs of plasma-derived
      medicinal products obtained by national plasma, industrial costs currently
      sustained by National Health Service for contract fractionation were taken into
      account. RESULTS: The production costs of plasma-derived medicinal products
      obtained from national plasma showed a huge variability among blood
      establishments, which was much lower after standardization. The new suggested
      plasma tariffs were quite similar to those currently in force. Comparing the
      overall costs theoretically sustained by the National Health Service for plasma
      derived medicinal products obtained from national plasma to current commercial
      costs, demonstrates that the national blood system could gain a 10% cost saving
      if it were able to produce plasma for fractionation within the standard costs
      defined in this study. DISCUSSION: Achieving national self-sufficiency through
      the production of plasma-derived medicinal products from national plasma, is a
      strategic goal of the National Health Service which must comply not only with
      quality, safety and availability requirements but also with the increasingly
      pressing need for economic sustainability.

PMID- 24333308
TI  - Clinical use of albumin.

PMID- 24333309
TI  - Plasma-derived medicinal products: demand and clinical use.

PMID- 24333310
TI  - The demand for human albumin in Italy.

PMID- 24333311
TI  - Clinical use of polyvalent immunoglobulins.

PMID- 24333312
TI  - Polyvalent immunoglobulins: challenges and perspectives.

PMID- 24333313
TI  - The demand for polyvalent immunoglobulins in Italy.

PMID- 24333315
TI  - The evolution of the regulatory framework for the plasma and plasma-derived
      medicinal products system in Italy.

PMID- 24333314
TI  - Clinical use of factor VIII and factor IX concentrates.

PMID- 24333317
TI  - Present and future challanges in the treatment of haemophilia: a clinician's
      perspective.

PMID- 24333316
TI  - The demand for factor VIII and for factor IX and the toll fractionation product
      surplus management.

PMID- 24333318
TI  - Present and future challenges in the treatment of haemophilia: the patient's
      perspective.

PMID- 24333319
TI  - Clinical use and the Italian demand for antithrombin.

PMID- 24333320
TI  - Clinical use and the Italian demand for prothrombin complex concentrates.

PMID- 24333321
TI  - Water-loss dehydration and aging.
AB  - This review defines water-loss and salt-loss dehydration. For older people serum
      osmolality appears the most appropriate gold standard for diagnosis of water-loss
      dehydration, but clear signs of early dehydration have not been developed. In
      older adults, lower muscle mass, reduced kidney function, physical and cognitive
      disabilities, blunted thirst, and polypharmacy all increase dehydration risk.
      Cross-sectional studies suggest a water-loss dehydration prevalence of 20-30% in
      this population. Water-loss dehydration is associated with higher mortality,
      morbidity and disability in older people, but evidence is still needed that this
      relationship is causal. There are a variety of ways we may be able to help older
      people reduce their risk of dehydration by recognising that they are not drinking
      enough, and being helped to drink more. Strategies to increase fluid intake in
      residential care homes include identifying and overcoming individual and
      institutional barriers to drinking, such as being worried about not reaching the
      toilet in time, physical inability to make or to reach drinks, and reduced social
      drinking and drinking pleasure. Research needs are discussed, some of which will
      be addressed by the FP7-funded NU-AGE (New dietary strategies addressing the
      specific needs of elderly population for a healthy ageing in Europe) trial. 

PMID- 24333322
TI  - Novel di-aryl-substituted isoxazoles act as noncompetitive inhibitors of the
      system Xc(-) cystine/glutamate exchanger.
AB  - The system xc(-) antiporter is a plasma membrane transporter that mediates the
      exchange of extracellular l-cystine with intracellular l-glutamate. This exchange
      is significant within the context of the CNS because the import of l-cystine is
      required for the synthesis of the antioxidant glutathione, while the efflux of l
      glutamate has the potential to contribute to either excitatory signaling or
      excitotoxic pathology. Changes in the activity of the transport system have been
      linked to the underlying pathological mechanisms of a variety of CNS disorders,
      one of the most prominent of which is its highly enriched expression in glial
      brain tumors. In an effort to produce more potent system xc(-) blockers, we have
      been using amino-3-carboxy-5-methylisoxazole propionic acid (ACPA) as a scaffold
      for inhibitor development. We previously demonstrated that the addition of
      lipophilic aryl groups to either the #4 or #5 position on the isoxazole ring
      markedly increased the inhibitory activity at system xc(-). In the present work a
      novel series of analogues has been prepared in which aryl groups have been
      introduced at both the #4 and #5 positions. In contrast to the competitive action
      of the mono-substituted analogues, kinetic analyses indicate that the di
      substituted isoxazoles block system xc(-)-mediated uptake of (3)H-l-glutamate
      into SNB-19 cells by a noncompetitive mechanism. These new analogues appear to be
      the first noncompetitive inhibitors identified for this transport system, as well
      as being among the most potent blockers identified to date. These diaryl
      isoxazoles should be of value in assessing the physiological roles and molecular
      pharmacology of system xc(-). 

PMID- 24333323
TI  - Comparison of the neuroprotective potential of Mucuna pruriens seed extract with
      estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice
      model.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative disease
      found in the aging population. Currently, many studies are being conducted to
      find a suitable and effective cure for PD, with an emphasis on the use of herbal
      plants. In Ayurveda, Mucuna pruriens (Mp), a leguminous plant, is used as an anti
      inflammatory drug. In this study, the neuroprotective effect of an ethanolic
      extract of Mp seed is evaluated in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) model of PD and compared to estrogen, a well reported
      neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were
      randomly divided into four groups: Control, MPTP, MPTP+Mp and MPTP+estrogen. The
      behavioural recovery in both Mp and estrogen treated mice was investigated using
      the rotarod, foot printing and hanging tests. The recovery of dopamine neurons in
      the substantia nigra (SN) region was estimated by tyrosine hydroxylase (TH),
      immunostaining. Additionally inducible nitric oxide synthase (iNOS) and glial
      fibrillary acidic protein (GFAP) immunoreactivity was evaluated to assess the
      level of oxidative damage and glial activation respectively. The levels of
      dopamine and its metabolite in the nigrostriatal region were measured by HPLC. Mp
      treatment restored all the deficits induced by MPTP more effectively than
      estrogen. Mp treatment recovered the number of TH-positive cells in both the SN
      region and the striatum while reducing the expression of iNOS and GFAP in the SN.
      Treatment with Mp significantly increased the levels of dopamine, DOPAC and
      homovanillic acid compared to MPTP intoxicated mice. Notably, the effect of Mp
      was greater than that elicited by estrogen. Mp down regulates NO production,
      neuroinflammation and microglial activation and all of these actions contribute
      to Mp's neuroprotective activity. These results suggest that Mp can be an
      effective treatment for neurodegenerative diseases, especially PD by decreasing
      oxidative stress and possibly by implementing neuronal and glial cell crosstalk. 

PMID- 24333324
TI  - Expression of the System N transporter (SNAT5/SN2) during development indicates
      its plausible role in glutamatergic neurotransmission.
AB  - Solute neutral amino acid transporter 5 (SNAT5/SN2) is a member of the System N
      family, expressed in glial cells in the adult brain, able to transport glutamine,
      histidine or glycine among other substrates. Its tight association with synapses
      and its electroneutral mode of operation that allows the bidirectional movement
      of substrates, supports the idea that this transporter participates in the
      function of the glutamine-glutamate cycle between neurons and glia. Moreover,
      SNAT5/SN2 might contribute to the regulation of glycine concentration in
      glutamatergic synapses and, therefore, to the functioning of the N-methyl-d
      aspartate (NMDA) subtype of glutamate receptors. Ontogenic maturation of these
      synapses occurs postnatally through the coordinate expression of a large number
      of receptors, transporters, structural and regulatory proteins that ensure the
      correct operation of the excitatory pathways in the central nervous system. Since
      the temporal pattern of expression of SNAT5/SN2 is unknown, we analyzed it by
      immunoblot and immunohistochemical techniques. Results indicate that the
      expression of SNAT5/SN2 is triggered between the second and third postnatal week
      in the cerebral cortex, in parallel to the expression of the vesicular glutamate
      transporter vGLUT1 and the glial glutamate transporter GLT1/EAAT2. In the
      cerebellum, this process occurs about one week later than in the cerebral cortex.
      Immunohistochemical staining of cortical sections shows that from postnatal day
      14 to adulthood the transporter was expressed exclusively in glial cells. Our
      results are consistent with the idea that SNAT5/SN2 expression is coordinated
      with that of other proteins necessary for the operation of glutamatergic synapses
      and reinforce the existence of a regulatory cross-talk between neurons and glia
      that orchestrates the building up of these synapses. 

PMID- 24333326
TI  - Laparoscopic removal of perforated tubal occlusion micro-inserts.

PMID- 24333325
TI  - Extrinsic sphingosine 1-phosphate activates S1P5 and induces autophagy through
      generating endoplasmic reticulum stress in human prostate cancer PC-3 cells.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that binds to a
      family of G protein-coupled receptors (GPCRs), termed S1P1-S1P5. Our previous
      study has reported that S1P induces autophagy in human prostate cancer PC-3 cell.
      In addition, S1P-induced autophagy plays a prosurvival role in PC-3 cells.
      Accumulating evidence has shown that the autophagy responses triggered by ER
      stress signaling have cytoprotective effects. Thus, we attempted to investigate
      whether S1P-induced autophagy is a result of triggering ER stress in PC-3 cells.
      By monitoring XBP-1 mRNA splicing, a characteristic of ER stress, we demonstrate
      that S1P triggers ER stress in a concentration-dependent and time-dependent
      manner. Moreover, DiH S1P, a membrane-nonpermeable S1P analog without
      intracellular effects also enhances ER stress. Meanwhile, we also show that S1P5
      is required for S1P-induced ER stress by using RNA interference experiments.
      Furthermore, signaling analyses revealed that PI3K, PLC, and ROS production were
      involved in S1P's effects on ER stress induction. On the other hand, knockdown of
      XBP-1 abolished S1P-induced autophagy. In summary, our results demonstrate for
      the first time that the extracellular S1P-triggered ER stress is responsible for
      autophagy induction in PC-3 cells. 

PMID- 24333327
TI  - Change to a standardized airway clearance protocol for children with
      bronchiolitis leads to improved care.
AB  - Nurses at a pediatric hospital identified the liberal utilization of deep
      nasopharyngeal (NP) suction as the primary airway clearance modality in young
      children with bronchiolitis. This invasive practice lacked supporting evidence
      and a standardized approach. Nurses created an interdisciplinary team to develop
      a less invasive airway clearance protocol. Data from 2years, both pre and post
      protocol implementation, were analyzed. An 11% decrease in deep NP suctioning
      resulted in improved or unchanged balancing measures and perceptions of quality
      of care. 

PMID- 24333328
TI  - On the role of eye movement monitoring and discouragement on inhibition of return
      in a go/no-go task.
AB  - Inhibition of return (IOR) most often describes the finding of increased response
      times to cued as compared to uncued targets in the standard covert orienting
      paradigm. A perennial question in the IOR literature centers on whether the
      effect of IOR is on motoric/decision-making processes (output-based IOR),
      attentional/perceptual processes (input-based IOR), or both. Recent data converge
      on the idea that IOR is an output-based effect when eye movements are required or
      permitted whereas IOR is an input-based effect when eye movements are monitored
      and actively discouraged. The notion that the effects of IOR may be fundamentally
      different depending on the activation state of the oculomotor system has been
      challenged by several studies demonstrating that IOR exists as an output-, or
      output- plus input-based effect in simple keypress tasks not requiring oculomotor
      responses. Problematically, experiments in which keypress responses are required
      to visual events rarely use eye movement monitoring let alone the active
      discouragement of eye movement errors. Here, we return to an experimental method
      implemented by Ivanoff and Klein (2001) whose results demonstrated that IOR
      affected output-based processes when, ostensibly, only keypress responses
      occurred. Unlike Ivanoff and Klein, however, we assiduously monitor and
      discourage eye movements. We demonstrate that actively discouraging eye movements
      in keypress tasks changes the form of IOR from output- to input-based and, as
      such, we strongly encourage superior experimental control over or consideration
      of the contribution of eye movement activity in simple keypress tasks exploring
      IOR. 

PMID- 24333329
TI  - Type I interferons up-regulate the expression and signalling of p75 NTR/TrkA
      receptor complex in differentiated human SH-SY5Y neuroblastoma cells.
AB  - Both type I interferons (IFNs) and neurotrophins regulate neuroadaptive
      responses, but relatively little is known on the interaction between these two
      classes of regulatory proteins. Here we investigated the effect of IFN-beta on
      the expression and functional activity of the common neurotrophin receptor p75NTR
      and the nerve growth factor (NGF) receptor TrkA. In differentiated human SH-SY5Y
      neuroblastoma cells prolonged exposure to IFN-beta up-regulated p75NTR and TrkA
      levels, failed to affect the content of sortilin, a p75NTR co-receptor, and,
      consistent with our previous finding, down-regulated the brain-derived
      neurotrophic factor receptor TrkB. Quantitative real time RT-PCR indicated that
      IFN-beta increased p75NTR and TrkA mRNA levels. In control and IFN-beta treated
      cells proNGF failed to induce c-Jun N-terminal kinase and nuclear factor/kB
      activation, two p75NTR/sortilin signalling pathways mediating neuronal death. On
      the other hand, IFN-beta treatment enhanced TrkA autophosphorylation and
      signalling induced by NGF and proNGF. Knockdown of p75NTR by siRNA reduced TrkA
      activation by proNGF and a subnanomolar concentration of NGF, whereas co
      immunoprecipitation indicated close association of p75NTR and TrkA. Co-treatment
      with either NGF or proNGF reduced IFN-beta pro-apoptotic and anti-neurotrophic
      effects. Similarly, in primary mouse hippocampal neurons IFN-beta increased
      p75NTR and TrkA expression, down-regulated TrkB and enhanced NGF-induced
      phosphorylation of the pro-survival protein kinase Akt. The data demonstrate that
      in neuronal cells IFN-beta differentially affects the expression and signalling
      of neurotrophin receptors and suggest that the up-regulation of the p75NTR/TrkA
      signalling complex may constitute a novel mechanism by which this cytokine
      selectively attenuates its pro-apoptotic effect in NGF-responsive cells. 

PMID- 24333330
TI  - Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the
      Nrf2/ARE signaling pathway.
AB  - There is increasing evidence that oxidative stress is critically involved in the
      pathogenesis of Parkinson's disease (PD), suggesting that pharmacological
      targeting of the antioxidant machinery may have therapeutic value. Naringenin, a
      natural flavonoid compound, has been reported to possess neuroprotective effect
      against PD related pathology; however the mechanisms underlying its beneficial
      effects are poorly defined. Thus, the purpose of the present study was to
      investigate the potential neuroprotective role of naringenin and to delineate its
      mechanism of action against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in
      models of PD both in vitro and in vivo. Naringenin treatment resulted in an
      increase in nuclear factor E2-related factor 2 (Nrf2) protein levels and
      subsequent activation of antioxidant response element (ARE) pathway genes in SH
      SY5Y cells and in mice. Exposure of SH-SY5Y cells to naringenin provided
      protection against 6-OHDA-induced oxidative insults that was dependent on Nrf2,
      since treatment with Nrf2 siRNA failed to block against 6-OHDA neurotoxicity or
      induce Nrf2-dependent cytoprotective genes in SH-SY5Y cells. In mice, oral
      administration of naringenin resulted in significant protection against 6-OHDA
      induced nigrostriatal dopaminergic neurodegeneration and oxidative damage. Our
      results indicate that activation of Nrf2/ARE signaling by naringenin is strongly
      associated with its neuroprotective effects against 6-OHDA neurotoxicity and
      suggest that targeting the Nrf2/ARE pathway may be a promising approach for
      therapeutic intervention in PD. 

PMID- 24333332
TI  - A miniaturized assay for measuring small molecule phosphorylation in the presence
      of complex matrices.
AB  - We describe here a simple, miniaturized radiation-based phosphorylation assay
      that can be used to monitor phosphorylation of a diverse range of small molecule
      substrates in the presence of purified and crude enzyme preparations. Ba(OH)2 and
      ZnSO4 are used to terminate phosphoryl transfer and to precipitate selectively
      the phosphorylated reaction product in a single step; non-phosphorylated
      substrate is removed by filtration prior to quantification. The key advantages
      over alternative radiation-based assays are that: (i) high-energy/short-lived
      radioactive emitters are not required; (ii) high-quality data can be obtained
      without the need for high radioactivity concentrations; and (iii) the assay is
      compatible with high-throughput applications. 

PMID- 24333331
TI  - A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid
      induced spatial memory improvements in young rats.
AB  - The increase in incidence and prevalence of neurodegenerative diseases highlights
      the need for a more comprehensive understanding of how food components may affect
      neural systems. In particular, flavonoids have been recognized as promising
      agents capable of influencing different aspects of synaptic plasticity resulting
      in improvements in memory and learning in both animals and humans. Our previous
      studies highlight the efficacy of flavonoids in reversing memory impairments in
      aged rats, yet little is known about the effects of these compounds in healthy
      animals, particularly with respect to the molecular mechanisms by which
      flavonoids might alter the underlying synaptic modifications responsible for
      behavioral changes. We demonstrate that a 3-week intervention with two dietary
      doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates
      spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young
      healthy rats. We show for the first time that these behavioral improvements are
      linked to increased levels in the polysialylated form of the neural adhesion
      molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known
      to be required for the establishment of durable memories. We observed parallel
      increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7
      mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of
      glutamate signaling following flavonoid intervention. This is further
      strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF
      signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in
      inducing changes in the strength of hippocampal synaptic connections that
      underlie learning. Collectively, the present data supports a new role for PSA
      NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and
      memory, contributing further to the growing body of evidence suggesting
      beneficial effects of flavonoids in cognition and brain health. 

PMID- 24333333
TI  - Cilostazol promotes production of melanin by activating the microphthalmia
      associated transcription factor (MITF).
AB  - Cilostazol, a licensed clinical drug for the treatment of intermittent
      claudication, is a phosphodiesterase (PDE) inhibitor that selectively inhibits
      PDE3, a cAMP-degrading enzyme, thus elevating levels of intracellular cAMP. It
      has been reported that pigment production by melanocytes both tans the skin and
      protects against skin cancers. The effects of cilostazol in melanogenesis are as
      yet unknown. In this study, treatment with cilostazol was found to promote the
      production of melanin as well as increase both Tyrosinase enzymatic activity and
      expression of the Tyrosinase gene. Importantly, we also found that cilostazol led
      to increased expression of the microphthalmia-associated transcription factor
      (MITF), the "master regulator" of both melanocyte differentiation and pigment
      production. Interestingly, knockdown of MITF using siRNA abolished the effects of
      cilostazol in melanogenesis, thereby suggesting that MITF might play a critical
      role in melanogenesis. Increased expression of MITF was abolished by treatment
      with H-89, a specific protein kinase A (PKA) inhibitor, thereby suggesting that
      the PKA pathway plays a critical role in cilostazol-induced expression of MITF.
      Cilostazol in fact enhanced expression of p-CREB, which was inhibited by H-89.
      Moreover, this cilostazol-induced increase in expression of MITF was inhibited by
      downregulation of CREB using CREB siRNA. These data suggest that induction of
      MITF via the PKA/CREB pathway plays a critical role in cilostazol-induced
      production of melanin in B16-F10 melanoma cells. 

PMID- 24333334
TI  - Experimental challenges of sense codon reassignment: an innovative approach to
      genetic code expansion.
AB  - The addition of new and versatile chemical and biological properties to proteins
      pursued through incorporation of non-canonical amino acids is at present
      primarily achieved by stop codon suppression. However, it is critical to find new
      "blank" codons to increase the variety and efficiency of such insertions, thereby
      taking 'sense codon recoding' to center stage in the field of genetic code
      expansion. Current thought optimistically suggests the use of the pyrrolysine
      system coupled with re-synthesis of genomic information towards achieving sense
      codon reassignment. Upon review of the serious experimental challenges reported
      in recent studies, we propose that success in this area will depend on the re
      synthesis of genomes, but also on 'rewiring' the mechanism of protein synthesis
      and of its quality control. 

PMID- 24333335
TI  - Sphingolipid levels crucially modulate lateral microdomain organization of plasma
      membrane in living yeast.
AB  - We report sphingolipid-related reorganization of gel-like microdomains in the
      plasma membrane of living Saccharomyces cerevisiae using trans-Parinaric acid (t
      PnA) and 1,6-diphenyl-1,3,5-hexatriene (DPH). Compared to control, the gel-like
      domains were significantly reduced in the membrane of a sphingolipid-deficient
      lcb1-100 mutant. The same reduction resulted from sphingolipid depletion by
      myriocin. The phenotype could be reverted when a myriocin-induced block in
      sphingolipid biosynthesis was bypassed by exogenous dihydrosphingosine. Lipid
      order of less-ordered membrane regions decreased with sphingolipid depletion as
      well, as documented by DPH fluorescence anisotropy. The data indicate that
      organization of lateral microdomains is an essential physiological role of these
      structural lipids. 

PMID- 24333336
TI  - Resveratrol suppresses prostaglandin F(2alpha)-induced osteoprotegerin synthesis
      in osteoblasts: inhibition of the MAP kinase signaling.
AB  - Resveratrol, a natural polyphenol abundantly found in grape skins and red wine,
      possesses various beneficial properties for human health. In the present study,
      we investigated the mechanism underlying the effects of prostaglandin F2alpha
      (PGF2alpha) on osteoprotegerin (OPG) synthesis and of resveratrol on the OPG
      synthesis in osteoblast-like MC3T3-E1 cells. PGF2alpha stimulated both the
      release of the OPG protein and the expression of OPG mRNA. Treatment with
      PD98059, SB203580 and SP600125, specific inhibitors of MEK1/2, p38 mitogen
      activated protein (MAP) kinase and stress-activated protein kinase/c-jun N
      terminal kinase (SAPK/JNK) all suppressed the OPG release induced by PGF2alpha.
      Resveratrol also significantly reduced the PGF2alpha-stimulated OPG release and
      the mRNA levels of OPG. Similarly, treatment with SRT1720, an activator of SIRT1,
      also suppressed the PGF2alpha-stimulated OPG release. Resveratrol and SRT1720
      both attenuated the phosphorylation of p44/p42 MAP kinase, MEK1/2, Raf-1, p38 MAP
      kinase and SAPK/JNK induced by PGF2alpha. These findings strongly suggest that
      resveratrol suppresses PGF2alpha-stimulated OPG synthesis by inhibiting the MAP
      kinase pathways in osteoblasts, and that the effect is mediated via SIRT1
      activation. 

PMID- 24333337
TI  - An efficient method to isolate and culture mouse Kupffer cells.
AB  - Kupffer cells (KCs) play an essential role in the physiological and pathological
      functions of the liver. Although the isolation methods of KCs have been well
      described, most of them are sophisticated and time-consuming. In addition, these
      methods are mainly used for isolating the KCs of the human and rat. In this
      study, a three-step procedure was applied to isolate KCs in sufficient number and
      purity from mouse liver, including the techniques of enzymatic tissue treatment,
      gradient centrifugation, and selective adherence. F4/80 immunofluorescence and
      flow cytometry were used for cell identification. The combination method resulted
      in a satisfactorily high yield of 5-6*10(6) KCs per liver, over 92.0% positive
      for F4/80 and 98.5% viable cells. After 24h of culturing, the KCs showed typical
      macrophage morphologic features such as irregular shape, transparent cytoplasm
      and kidney-like nucleus. The phagocytic assay showed that the isolated cells
      exhibited strong phagocytosis activity. The KCs we isolated were functionally
      intact and exhibited a concentration dependent TNF-alpha production induced by
      LPS. The method we described is an effective method to isolate mouse KCs in high
      purity and yield, which consuming fewer collagenase and time without altering the
      functional capacity of the KCs. 

PMID- 24333338
TI  - A higher frequency of CD4+CXCR5+ T follicular helper cells in patients with newly
      diagnosed IgA nephropathy.
AB  - The frequency of different subsets of CD4(+)CXCR5(+) TFH cells and the levels of
      serum cytokines were examined in 24 patients with newly diagnosed IgAN before and
      8-12 weeks after treatment and in 12 healthy controls (HC). In comparison with
      HC, significantly higher percentages of CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+),
      CD4(+)CXCR5(+)PD-1(+) TFH cells and higher levels of serum IL-17A, IFN-gamma, IL
      2, IL-10, IL-4 and IL-21 were detected in IgAN patients. The percentages of
      CD4(+)CXCR5(+) TFH cells were negatively correlated with the values of eGFR and
      CD4(+)CXCR5(+)PD-1(+) TFH cells were correlated positively with the levels of
      serum IL-21 and Gd-IgA1 as well as 24h urinary proteins. Treatment with
      prednisone significantly reduced the frequency of CD4(+)CXCR5(+) and
      CD4(+)CXCR5(+)PD-1(+) TFH cells and the levels of serum IL-21, but increased IL-4
      and IL-10 in those patients. A higher frequency of CD4(+)CXCR5(+) TFH cells
      existed in patients with IgAN and may be associated with the development of IgAN.

PMID- 24333339
TI  - Cross-presentation by human dendritic cell subsets.
AB  - Dendritic cells (DCs) are a heterogeneous population of professional antigen
      presenting cells. Several murine DC subsets differ in their phenotype and
      functional properties, in particular in their ability to cross-present antigens
      (i.e. to present exogenous antigens on their MHC class I molecules). In humans,
      distinct DC subpopulations have also been identified but whether some human DC
      subsets are also specialized at cross-presentation remains debated. Here we
      review the DC subsets that have been identified in humans and we discuss recent
      work that addresses their ability to cross-present antigens and their efficiency
      for CD8(+) T cells activation. 

PMID- 24333340
TI  - Identification of CD244-expressing myeloid-derived suppressor cells in patients
      with active tuberculosis.
AB  - Development of active TB is accompanied by immune suppression and the underlining
      mechanisms have been explored extensively in recent years. MDSCs are a
      heterogeneous group of immature and progenitor myeloid cells with strong
      immunosuppressive ability for both natural and adaptive immunity. In our analysis
      of CD244 (2B4)-expressing cells in PBMCs from patients with active TB, a CD3(
      )CD244(high) subpopulation was identified. A match of cell population in flow
      cytometry showed that nearly all CD3(-)CD244(high) cells were CD3(-)HLA-DR(
      )CD11b(int)CD33(+) cells. The CD3(-)CD244(high) cell population has phenotypes of
      CD3(-)CD19(-)CD56(-)CD15(-)CD66b(-)CD33(+)CD11b(+)CD14(-)HLA-DR(neg/low), which
      was consistent with MDSCs in humans as previously reported. Patients with active
      TB had higher frequencies of CD3(-)CD244(high) cells as compared with healthy
      controls. The CD3(-)CD244(high) cell population had high levels of NOS2
      expression and was negatively correlated with activation and effective molecule
      production of CD4(+) and CD8(+) T cells. In conclusion, CD3(-)CD244(high) cells
      had phenotypes of MDSCs and CD244 might be used as a marker for human CD3(-)HLA
      DR(-)CD11b(int)CD33(+) MDSCs. 

PMID- 24333341
TI  - Different treatment settings of Granulocyte-Colony Stimulating Factor and their
      impact on T cell-specific immune response in experimental stroke.
AB  - BACKGROUND: Cerebral ischemia is associated with infectious complications due to
      immunosuppression and decreased T lymphocyte activity. G-CSF, which has
      neuroprotective properties, is known to modulate inflammatory processes after
      induced stroke. The aim of our study was to investigate the impact of G-CSF in
      experimental stroke and to compare two different modes of treatment, focusing on
      circulating T lymphocytes. METHODS: Cerebral ischemia was induced in Wistar rats
      by occlusion of the middle cerebral artery, followed by reperfusion after 1h. G
      CSF was applied either as a single dose 30 min after occlusion, or daily for
      seven days. Silver staining was used to determine infarct size. T lymphocytes in
      the peripheral blood were measured before and 7 days after induced cerebral
      ischemia by flow cytometry. In addition, migration of CD3-expressing T
      lymphocytes into the brain was investigated by immunohistochemistry. RESULTS:
      Both single dose and daily treatment with G-CSF significantly reduced infarct
      size. A significant improvement of neurological outcome was only observed after
      single application of G-CSF. While a decrease in peripheral T lymphocytes was
      detected seven days after induced stroke, no reduction was observed in the G-CSF
      treated groups. Apart from that, G-CSF significantly reduced the number of brain
      migrated T lymphocytes in both treatment settings as compared to vehicle.
      CONCLUSION: A single dose of G-CSF exerted neuroprotective effects in ischemic
      stroke, which were less pronounced after daily G-CSF application. Both treatment
      strategies inhibited stroke-induced reduction of T lymphocytes in peripheral
      blood, which may have contributed to the reduction of infarct size.

PMID- 24333342
TI  - Perspectives in immunopharmacology: the future of immunosuppression.
AB  - Modulation of immune responses for therapeutic purposes is a particularly
      relevant area, given the central role of anomalous immunity in a wide variety of
      diseases, from the most typically immune-related syndromes (autoimmune diseases,
      allergy and asthma, immunodeficiencies) to those in which altered immunity and
      inflammation define the pathological outcomes (chronic infections, tumors,
      chronic inflammatory and degenerative diseases, metabolic disorders, etc.). This
      brief review will summarize some of the most promising perspectives of
      immunopharmacology, in particular in the area of immunosuppression, by
      considering the following aspects: 

PMID- 24333343
TI  - Evaluation of recombinant fusion protein comprising dog zona pellucida
      glycoprotein-3 and Izumo and individual fragments as immunogens for
      contraception.
AB  - Vaccines based on gamete specific proteins have been proposed for fertility
      inhibition. In the present study, immunogenicity and contraceptive potential of
      E. coli-expressed recombinant fusion protein TT-KK-ZP3-GGG-Iz, comprising
      promiscuous T cell epitope of tetanus toxoid (TT) followed by dilysin linker
      (KK), a fragment of dog zona pellucida glycoprotein-3 (ZP3), triglycine spacer
      (GGG) and a fragment of dog Izumo (Iz) without any affinity tag has been
      evaluated in female FvB/J mice. In addition, recombinant TT-KK-ZP3 and Izumo
      linked to the promiscuous T cell epitope of bovine RNase (bRNase-KK-Iz) and their
      physical mixture were also used. SDS-PAGE and immunoblot studies revealed ~32kDa
      band corresponding to TT-KK-ZP3-GGG-Iz, ~22kDa band of TT-KK-ZP3 and ~11kDa band
      of bRNase-KK-Iz. Groups of mice immunized with the above recombinant proteins led
      to the generation of high antibody titres against the respective proteins.
      Immunization with recombinant TT-KK-ZP3-GGG-Iz generated higher antibody titre as
      compared to mice immunized with physical mixture of TT-KK-ZP3 and bRNase-KK-Iz.
      Antibodies against TT-KK-ZP3-GGG-Iz and TT-KK-ZP3 recognized mouse and dog ZP and
      those against TT-KK-ZP3-GGG-Iz and bRNase-KK-Iz recognized mouse and dog acrosome
      reacted sperm in an indirect immunofluorescence assay. Immune sera from groups of
      mice immunized with the above recombinant proteins led to a significant reduction
      in mouse in vitro fertilization. Mating studies revealed significant reduction in
      fertility as compared to adjuvant control group. Highest infertility was observed
      in group of mice immunized with TT-KK-ZP3 followed by TT-KK-ZP3-GGG-Iz.
      Infertility was associated with the antibody titres against ZP3, whereas no
      association in the inhibition of fertility and antibody titres against Izumo was
      observed. In conclusion, these studies revealed the contraceptive potential of
      ZP3, which could not be further enhanced by the inclusion of Izumo. 

PMID- 24333344
TI  - Antibody but not memory B-cell responses are tuned-down in vertically HIV-1
      infected children and young individuals being vaccinated yearly against
      influenza.
AB  - Yearly immunization against seasonal influenza is highly recommended for HIV-1
      infected individuals but evaluating the success of vaccination by serological
      markers may not be fully informative in this population. Recently, it has been
      hypothesized that the generation of long-lasting immune responses may depend on
      whether similar antigens challenge the immune system frequently and
      intermittently. In the present study, in order to search for additional
      correlates of vaccine-induced protective immunity and to further dissect this
      theory, both humoral and memory B-cell responses to the trivalent 2012-2013
      seasonal influenza vaccination has been evaluated by strain-specific (separately
      for H1N1, H3N2 and B strain) standard hemagglutination inhibition (HI) assay and
      B-cell enzyme-linked immunosorbent spot (ELISpot) in a cohort of vertically HIV-1
      infected children and young individuals as compared to age-matched healthy
      controls. A high number of HIV-1 infected individuals had protective antibody
      levels prior to vaccination and showed low seroconversion rates after vaccination
      as compared to healthy controls. On the contrary, similar frequencies of
      influenza-specific memory B-cells were detected by B-cell ELISpot in both groups
      suggesting that an adequate B-cell response has been elicited. Data from the H1N1
      strain, which is recurrent in seasonal influenza vaccines since 2009, pointed out
      decreasing antibody but not memory B-cell responses for HIV-1 infected patients
      being vaccinated for a greater number of years. Further investigations are
      required to standardize the influenza-specific B-cell ELISpot and to understand
      whether it could be used routinely as an additional tool to evaluate response to
      influenza vaccination in immune-compromised individuals being vaccinated yearly. 

PMID- 24333345
TI  - A mucosal adjuvant for the inactivated poliovirus vaccine.
AB  - The eradication of poliovirus from the majority of the world has been achieved
      through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the
      live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at
      preventing paralytic poliomyelitis, however, they also have significant
      differences. Most importantly for this work is the risk of revertant virus from
      OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and
      others have previously described the use of an alphavirus-based adjuvant that can
      induce a mucosal immune response to a co-administered antigen even when delivered
      at a non-mucosal site. In this report, we describe the use of an alphavirus-based
      adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased
      systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three
      poliovirus serotypes in mice even when administered intramuscularly. Furthermore,
      GVI3000 significantly increased the potency of IPV in rat potency tests as
      measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000
      vaccine would reduce the dose of IPV needed and provide significantly improved
      mucosal immunity. This vaccine could be an effective tool to use in the
      poliovirus eradication campaign without risking the re-introduction of revertant
      poliovirus derived from OPV. 

PMID- 24333346
TI  - Pain assessment in animal models of osteoarthritis.
AB  - Assessment of pain in animal models of osteoarthritis is integral to
      interpretation of a model's utility in representing the clinical condition, and
      enabling accurate translational medicine. Here we describe behavioral pain
      assessments available for small and large experimental osteoarthritic pain animal
      models. 

PMID- 24333347
TI  - Constraint on di-nucleotides by codon usage bias in bacterial genomes.
AB  - It has been reported earlier that the relative di-nucleotide frequency (RDF) in
      different parts of a genome is similar while the frequency is variable among
      different genomes. So RDF is termed as genome signature in bacteria. It is not
      known if the constancy in RDF is governed by genome wide mutational bias or by
      selection. Here we did comparative analysis of RDF between the inter-genic and
      the coding sequences in seventeen bacterial genomes, whose gene expression data
      was available. The constraint on di-nucleotides was found to be higher in the
      coding sequences than that in the inter-genic regions and the constraint at the
      2nd codon position was more than that in the 3rd position within a genome.
      Further analysis revealed that the constraint on di-nucleotides at the 2nd codon
      position is greater in the high expression genes (HEG) than that in the whole
      genomes as well as in the low expression genes (LEG). We analyzed RDF at the 2nd
      and the 3rd codon positions in simulated coding sequences that were
      computationally generated by keeping the codon usage bias (CUB) according to
      genome G+C composition and the sequence of amino acids unaltered. In the
      simulated coding sequences, the constraint observed was significantly low and no
      significant difference was observed between the HEG and the LEG in terms of di
      nucleotide constraint. This indicated that the greater constraint on di
      nucleotides in the HEG was due to the stronger selection on CUB in these genes in
      comparison to the LEG within a genome. Further, we did comparative analyses of
      the RDF in the HEG rpoB and rpoC of 199 bacteria, which revealed a common pattern
      of constraints on di-nucleotides at the 2nd codon position across these bacteria.
      To validate the role of CUB on di-nucleotide constraint, we analyzed RDF at the
      2nd and the 3rd codon positions in simulated rpoB/rpoC sequences. The analysis
      revealed that selection on CUB is an important attribute for the constraint on di
      nucleotides at these positions in bacterial genomes. We believe that this study
      has come with major findings of the role of CUB on di-nucleotide constraint in
      bacterial genomes. 

PMID- 24333348
TI  - Detection of high-sensitivity troponin in outpatients with stable pulmonary
      hypertension identifies a subgroup at higher risk of adverse outcomes.
AB  - BACKGROUND: The detection of elevations in cardiorenal biomarkers, such as
      troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase
      associated lipocalins, are associated with poor outcomes in patients hospitalized
      with acute heart failure. Less is known about the association of these markers
      with adverse events in chronic right ventricular dysfunction due to pulmonary
      hypertension, or whether their measurement may improve risk assessment in the
      outpatient setting. METHODS AND RESULTS: We performed a cohort study of 108
      patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland,
      from 2007 to 2009. Cox proportional hazards analysis and receiver operating
      characteristic curves were used to determine predictors of mortality and
      hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during
      the median study period of 4.1 years. Independent predictors of mortality were:
      1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP
      (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001).
      Adjusted hazard analyses remained significant when hsTnT was added to a model
      with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of
      the model for death and rehospitalization (area under the receiver operating
      characteristic curve 0.81, 95% CI 0.73-0.90). CONCLUSIONS: Detection of troponin
      using a highly sensitive assay identifies a pulmonary hypertension subgroup with
      a poorer prognosis. hsTnT may also be used in a risk prediction model to identify
      patients at higher risk who may require escalation of targeted pulmonary
      vasodilator therapies and closer clinical surveillance.

PMID- 24333349
TI  - In vivo mutagenicity of arsenite in the livers of gpt delta transgenic mice.
AB  - While arsenic has been classified as a Group 1 human carcinogen by the
      International Agency for Research on Cancer (IARC), its mutagenicity has not been
      fully characterized in experimental animals. The aim of this study was to assess
      the in vivo mutagenicity of arsenite in C57BL/6J gpt delta mice. Male gpt delta
      mice were given drinking water containing sodium arsenite for 3 weeks, and the
      hepatic genome was assayed for mutations 2 weeks later. The gpt mutation assays
      showed a significant increase in mutation frequency in the liver following
      arsenite exposure. Sequence analysis revealed that 67% of mutations detected are
      G:C to A:T transitions and 5% are G:C to T:A transversions in the control group,
      and arsenite exposure resulted in a markedly higher rate of G:C to T:A
      transversions (46% of mutations detected). G:C to T:A transversions have been
      reported to be induced following formation of 8-hydroxy-2'-deoxyguanosine (8
      OHdG), a representative product that results from oxidative DNA damage. We also
      detected a significant increase in 8-OHdG in the livers of the mice exposed to
      arsenite. These results demonstrate that arsenite has mutagenicity in vivo and
      suggest that arsenite induces G:C to T:A transversions through oxidative-stress
      induced 8-OHdG formation. 

PMID- 24333350
TI  - Analysing 2010 resuscitation guidelines: what is the current level of evidence
      regarding simulation?

PMID- 24333351
TI  - The association between systolic blood pressure on arrival at hospital and
      outcome in adults surviving from out-of-hospital cardiac arrests of presumed
      cardiac aetiology.
AB  - BACKGROUND: The optimal blood pressure target following successful resuscitation
      from out-of-hospital cardiac arrest (OHCA) is uncertain. This study aimed to
      explore the association between level of systolic blood pressure (SBP) on arrival
      at hospital and survival to hospital discharge. METHODS: We analysed eligible
      OHCAs occurring between January 2003 and December 2011 from the Victorian
      Ambulance Cardiac Arrest Register (VACAR). Inclusion criteria were: adults (>=18
      years), presumed cardiac aetiology, not paramedic witnessed, and ROSC at hospital
      arrival. Multivariate logistic regression models were performed by initial rhythm
      (shockable/non-shockable) to examine the relationship between SBP at hospital
      arrival in 10 mmHg increments and survival to hospital discharge. Models were
      adjusted for known predictors of survival, including duration of arrest. RESULTS:
      Of 3620 eligible cases, 14% were hypotensive (SBP<90 mmHg) on hospital arrival
      (10% shockable and 19% non-shockable). For patients in shockable rhythms,
      discharge survival was maximal at 120-129 mmHg (54%), and in the adjusted model
      (>=120 mmHg as reference) SBP decrements below 90 mmHg were associated with lower
      survival: 80-89 mmHg AOR=0.49 (95% CI: 0.24-0.95); <80 mmHg AOR=0.24 (95% CI:
      0.10-0.61); unrecordable AOR=0.10 (95% CI: 0.04-0.30). In patients found in non
      shockable rhythms, SBP was not significant associated with discharge survival
      (AOR=1.01, 95% CI: 0.89-1.15). CONCLUSIONS: In an EMS system using intravenous
      adrenaline and fluids to maintain post-resuscitation SBP at 120 mmHg, hypotension
      on hospital arrival was relatively uncommon. However, in presumed cardiac OHCA
      patients with an initial shockable rhythm, SBPs below 90 mmHg was associated with
      significant lower odds of survival to hospital discharge. This level of
      hypotension may indicate patients who require more aggressive post-resuscitation
      blood pressure management.

PMID- 24333352
TI  - Nicole Suciu-Foca, PhD, Worthy Heir of Mendel and Medawar.

PMID- 24333353
TI  - Human immunology in the era of big data.

PMID- 24333355
TI  - Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in
      advanced ovarian cancer patients unsuitable for primary surgery: Safety and
      effectiveness.
AB  - OBJECTIVE: Three cycles of neoadjuvant chemotherapy (NACT) followed by interval
      debulking (ID) surgery is an alternative for patients with advanced ovarian
      cancer unresectable disease. This study aimed to determine the efficacy and
      safety of six cycles of NACT followed by cytoreduction. METHODS: Retrospective
      analysis of all patients with advanced epithelial ovarian cancer, tubal
      carcinoma, or primary peritoneal carcinoma treated with platinum based NACT
      between January 2008 and February 2012. RESULTS: Eighty-two patients underwent
      NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis,
      respectively. Their median age was 60 years (41-82). On histology, serous
      adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after
      debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed
      toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical
      complete response, 57.4% partial response, and 12.1% disease progression.
      Complete resection of all macroscopic and microscopic disease (R0) was performed
      in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients
      needed a second procedure due to operative complications and 18 (27.3%) needed
      blood transfusion after debulking. Over a median follow-up period of 19.2 months,
      median overall survival and chemotherapy-free interval were 37.5 months
      (confidence interval not reached) and 16 months, respectively. CONCLUSION: Six
      cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did
      not increase perioperative or postoperative complications in patients with stage
      IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this
      cohort was higher than that of those treated with ID surgery.

PMID- 24333356
TI  - Mismatch repair deficiency in ovarian cancer -- molecular characteristics and
      clinical implications.
AB  - DNA mismatch repair (MMR) deficiency is associated with increased risk of
      developing several types of cancer and is the most common cause of hereditary
      ovarian cancer after BRCA1 and BRCA2 mutations. While there has been extensive
      investigation of MMR deficiency in colorectal cancer, MMR in ovarian cancer is
      relatively under-investigated. This review summarizes the mechanism of MMR, the
      ways in which MMR deficiency can promote carcinogenesis in general and then
      assesses the available studies regarding MMR deficiency in ovarian cancers with
      specific emphasis on implications for disease incidence and therapy. The
      incidence of germline MMR gene mutations in ovarian cancer is only 2% but other
      mechanisms of gene inactivation mean that loss of expression of one of the seven
      main genes (MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2) occurs in up to 29% of
      cases. Both mutational and expression data suggest that MMR deficiency is more
      common in non-serous ovarian cancer. Some studies suggest an improved survival
      for patients with MMR deficiency compared to historical controls but these do not
      account for the preponderance of non-serous tumors. A number of in vitro studies
      have suggested that MMR deficiency is a cause of platinum resistance. To date
      this has not been categorically demonstrated in the clinic. Larger studies that
      account for stage of presentation and immunohistochemical subtype are required to
      assess the effect of MMR deficiency on survival and chemosensitivity.
      Investigation of MMR related synthetic lethality in colorectal cancer has
      identified dihydrofolate reductase, DNA polymerase beta and DNA polymerase gamma
      and PTEN-induced putative kinase 1 as synthetic lethal to certain MMR defects by
      causing accumulation of oxidative DNA damage. These synthetic lethal targets
      require tested and others should be sought within the context of MMR deficient
      ovarian cancer in an attempt to provide novel therapeutic strategies for these
      patients. 

PMID- 24333357
TI  - Application of the Carolina Framework for Cervical Cancer Prevention.
AB  - OBJECTIVE: The Carolina Framework for Cervical Cancer Prevention describes 4 main
      causes of cervical cancer incidence: human papillomavirus (HPV) infection, lack
      of screening, screening errors, and not receiving follow-up care. We present 2
      applications of the Carolina Framework in which we identify high-need counties in
      North Carolina and generate recommendations for improving prevention efforts.
      METHODS: We created a cervical cancer prevention need index (CCPNI) that ranked
      counties on cervical cancer mortality, HPV vaccine initiation and completion, Pap
      smear screening, and provision of Pap tests to rarely- or never-screened women.
      In addition, we conducted in-depth interviews with 19 key informants from
      programs and agencies involved in cervical cancer prevention in North Carolina.
      RESULTS: North Carolina's 100 counties varied widely on individual CCPNI
      components, including annual cervical cancer mortality (median 2.7/100,000 women;
      range 0.0-8.0), adolescent girls' HPV vaccine initiation (median 42%; range 15%
      62%), and Pap testing in the previous 3 years among Medicaid-insured adult women
      (median 59%; range 40%-83%). Counties with the greatest prevention needs formed 2
      distinct clusters in the northeast and south-central regions of the state.
      Interviews generated 9 recommendations to improve cervical cancer prevention in
      North Carolina, identifying applications to specific programs and policies in the
      state. CONCLUSIONS: This study found striking geographic disparities in cervical
      cancer prevention need in North Carolina. Future prevention efforts in the state
      should prioritize high-need regions as well as recommended strategies and
      applications in existing programs. Other states can use the Carolina Framework to
      increase the impact of their cervical cancer prevention efforts.

PMID- 24333358
TI  - Anxiolytic-like effects of phytol: possible involvement of GABAergic
      transmission.
AB  - Phytol, a branched chain unsaturated alcohol, is particularly interesting because
      it is an isolated compound from essential oils of different medicinal plants. The
      aim of this study was to evaluate the anxiolytic-like effects of phytol in animal
      models to clarify their possible action mechanism. After acute intraperitoneal
      treatment with phytol at doses of 25, 50 and 75 mg/kg behavioral models of open
      field, elevated-plus-maze, rota-rod, light-dark, marble-burying and pentobarbital
      sleeping time tests were utilized. In open field test, phytol (25, 50 and 75
      mg/kg) [p<0.01] increased the number of crossings and rearings. However, the
      number of groomings [p<0.01] was reduced. Likewise, the number of entries and the
      time spent in light space were increased [p<0.01] while the number of marble
      burying was decreased [p<0.001], in elevated-plus-maze, light-dark and marble
      burying tests, respectively. In motor activity test, phytol (75 mg/kg) impaired
      the rota-rod performance of mice [p<0.01]. In pentobarbital sleeping time test,
      phytol 75 mg/kg decreased for latency of sleeping and phytol (25, 50 and 75
      mg/kg) increased the sleep time when compared to negative control [p<0.05]. All
      these effects were reversed by pre-treatment with flumazenil (2.5mg/kg, i.p.),
      similarly to those observed with diazepam (2mg/kg, i.p.; positive control)
      suggesting that the phytol presents mechanism of action by interaction with the
      GABAergic system. These findings suggest that acute administration of phytol
      exerts an anxiolytic-like effect on mice. Furthermore, suppose that phytol
      interacts with GABAA receptor, probably at the receptor subtypes that mediate
      benzodiazepines effects, to produce sedative and anxiolytic activities.

PMID- 24333359
TI  - Activation of Nrf2-ARE signal pathway protects the brain from damage induced by
      epileptic seizure.
AB  - Epilepsy remains a major medical problem for which there is no effective
      treatment. Oxidative damage plays an important role in epilepsy pathogenesis and
      may represent a target for treatment of epilepsy. Recent studies have suggested
      that nuclear factor erythroid 2-related factor 2 (Nrf2) binds to antioxidant
      response element (ARE) to induce antioxidant and phase II detoxification enzymes
      under conditions of oxidative stress, which reduces oxidative damage and
      accumulation of toxic metabolites. This study evaluated the role of Nrf2-ARE
      signal pathway in protecting the brain from seizure-mediated damage. Wistar rats
      and Nrf2-deficient or control mice were chronic kindled in the amygdala.
      Sulforaphane (SF) was used to activate Nrf2-ARE signal pathway. The progression
      of kindling, the cognitive impairment and oxidative stress parameters were
      assessed to determine the extent of seizure-mediated brain damage. Our results
      indicate that activation Nrf2-ARE signal pathway with SF in hippocampus
      suppressed the progression of amygdala kindling, and also ameliorated the
      cognitive impairment and oxidative stress induced by epileptic seizure. These
      observations suggest that Nrf2-ARE signal pathway may represent a strategic
      target for epilepsy therapies. 

PMID- 24333360
TI  - Endosalpingiosis as it relates to tubal, ovarian and serous neoplastic tissues:
      an immunohistochemical study of tubal and Mullerian antigens.
AB  - OBJECTIVE: The origins and clinical significance of endosalpingiosis (ES),
      ectopic tubal epithelium, are not well understood. These investigations aim to
      characterize ES as it relates to normal fallopian tube, ovarian surface and
      serous neoplasms. METHODS: A retrospective review of pathology reports from all
      prophylactic gynecologic surgeries from 2000 to 2010 was performed to assess the
      frequency of ES. Twenty-one archival specimens of ES, 6 normal fallopian tubes, 9
      normal ovaries, 21 serous neoplasms and a commercially available ovarian tissue
      microarray were subjected to immunohistochemistry (IHC) with 11 tubal and
      Mullerian antigens. IHC staining was evaluated with a quantitative scoring system
      and scores were analyzed using MINITAB statistical software. RESULTS: ES was
      noted in 3.5% of pathologic specimens from 464 prophylactic surgeries. The
      majority of antigens showed no significant differences (p > 0.05) in median IHC
      scores between ES and normal fallopian tube epithelium (nFTE), while they were
      significantly different (p < 0.05) from the ovarian surface epithelium (OSE).
      Median IHC scores were unchanged in ES tissues regardless of the location of ES
      or the presence of a concurrent serous neoplasm. Three antigens emerged as
      contemporary tubal and ES biomarkers: phospho-Smad2, BCL2 and FOXJ1. All 3
      biomarkers were expressed in ES, nFTE and serous neoplasms, but not in OSE or
      other tumor types. CONCLUSION: This study provides immunophenotypic evidence that
      ES is more similar to the nFTE than OSE. Further, ES biomarker expression closely
      resembles serous neoplasms strengthening the growing body of evidence that all
      Mullerian serous carcinomas arise from tubal-like epithelium.

PMID- 24333361
TI  - Impact of facility volume on therapy and survival for locally advanced cervical
      cancer.
AB  - OBJECTIVE: Chemosensitizing radiation with brachytherapy is standard of care for
      treatment of locally advanced cervical cancer, an increasingly rare disease.
      Treatment facility volume has been correlated with outcome in many diseases.
      Treatment outcome and likelihood of receiving standard therapy in locally
      advanced cervical cancer based on facility volume were examined using a large
      national cancer database. METHODS: The National Cancer Data Base was queried for
      patients with stage IIB - IIIB cervical cancer from 1/1998 through 12/2010.
      Facility volumes were tallied. Overall survival was estimated using Kaplan-Meier
      method. Univariate and multivariable analyses were performed to determine
      variables affecting survival, receiving standard therapy, and total duration of
      radiotherapy. RESULTS: We identified a total of 27,660 patients who were treated
      at 1361 facilities. Thirty of the facilities (2.2%) treated the highest quartile
      volume of patients (>9.4 patients annually) while 1072 facilities (78.8%) treated
      <2.4 patients annually. The median age of patients was 53, the majority were
      Caucasian, treated in a metropolitan area, and of squamous cell histology. Median
      survival of patients treated at lowest- and highest-volume centers were 42.3
      months (95% CI 39.8-44.8) and 53.8 months (50.1-57.5), respectively (p < 0.001).
      The proportions of patients receiving brachytherapy and chemotherapy were 54.8%
      and 79.9%, respectively. On multivariable analysis, higher facility volume
      independently predicted improved survival (p = 0.022), increased likelihood of
      receiving brachytherapy (p < 0.0005) and chemotherapy (p = 0.013), and shorter
      time to radiotherapy completion (p < 0.0005). CONCLUSIONS: Patients with locally
      advanced cervical cancer treated at high volume centers are more likely to
      receive standard therapy, complete therapy sooner, and experience better
      survival.

PMID- 24333363
TI  - Metrics of the gynecologic oncology literature focused on cited utilization and
      costs.
AB  - OBJECTIVE: The newest findings on literature utilization relevant to gynecologic
      oncology were published by Thomson Reuters during June 2013 as determinants of
      journal standing. Our objective was to assess the different metrics reported for
      relative impact and cost for journals relevant to gynecologic oncology. METHODS:
      55 journals were evaluated for Impact Factor (IF), 5 Year IF, Immediacy Index,
      Cited Half Life, Eigenfactor (EF) Score, Article Influence (AI) scores and
      subscription costs obtained from publisher information. RESULTS: CA-A Cancer
      Journal for Clinicians had the highest IF (101.78) & AI (24.502). The top EF
      cancer-specific journals were the Journal of Clinical Oncology, Cancer Research,
      Clinical Cancer Research and Oncogene. Rankings for Gynecologic Oncology (409
      articles, 18,243 citations) were IF = 3.929, 43/55, EF = 0.038, 28/55, and AI =
      1.099, 44/55, all higher than the previous year. The IF improved from the 5 year
      IF in 31 journals, including Gynecologic Oncology, 29/31. Subscription costs for
      Gynecologic Oncology compared favorably to other journals. CONCLUSIONS: The high
      utilization of review information in CA-A Cancer Journal for Clinicians and
      Nature Review Cancer illustrated by the IF coupled with a relatively low number
      of articles and short cited half life indicates that they serve as a leading
      source of quoted cancer statistics (CA-A Cancer Journal for Clinicians). Rankings
      for Gynecologic Oncology and the International Journal of Gynecologic Cancer have
      improved. Regardless of specialty size, the Impact Factor for Gynecologic
      Oncology is respectably strong. The decreased IF in 44% of the journals may
      reflect the international economy's effect on cancer research.

PMID- 24333362
TI  - The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous
      ovarian carcinoma: a gynecologic Oncology Group study.
AB  - OBJECTIVES: The study objective was to determine the prognostic significance of
      serum CA-125 levels in patients with grade 1 serous ovarian carcinoma (SOC)
      enrolled in a Phase III study. METHODS: An ancillary analysis of a phase III
      study of women with advanced epithelial ovarian cancer treated with
      carboplatin/paclitaxel versus triplet or sequential doublet regimens. Grade 1 SOC
      was used as a surrogate for low-grade serous carcinoma. RESULTS: Among 3686
      enrolled patients, 184 (5%) had grade 1 disease and CA-125 levels available. For
      those with grade 1 SOC, the median patient age was 56.5; 87.3% had Stage III
      disease. Median follow-up was 102 months and there was no difference in pre
      chemotherapy CA-125 by treatment arm (P=0.91). Median pretreatment CA-125 for
      those with grade 1 SOC was lower (119.1) than for patients with grade 2-3 SOC
      (246.7; P<0.001). In those with grade 1, pretreatment CA-125 was not prognostic
      of outcome. However, patients with CA-125 levels that normalized after cycle 1, 2
      or 3 were 60-64% less likely to experience disease progression as compared to
      those who never normalized or normalized after 4 cycles (P <= 0.024).
      Normalization of CA-125 levels before the second cycle was negatively associated
      with death, with a HR of 0.45 (P=0.025). CONCLUSIONS: Pretreatment CA-125 level
      was significantly lower in women with grade 1 SOC compared to those with high
      grade SOC. While pretreatment CA-125 was not associated with survival, serial CA
      125 measurements during chemotherapy treatment were prognostic, with
      normalization before the second chemotherapy cycle associated with a decreased
      risk of death.

PMID- 24333364
TI  - Effect of the combinatory mixture of Rubus coreanus Miquel and Astragalus
      membranaceus Bunge extracts on ovariectomy-induced osteoporosis in mice and anti
      RANK signaling effect.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis is one of the most
      common disorders in women after menopause, which is linked to an estrogen
      deficiency and characterized by an excessive loss of trabecular bone. Rubus
      coreanus and Astragalus membranaceus have been used for their various
      pharmacological properties in Asia as a traditional medicine. The present study
      evaluated the anti-osteoporotic effects of the optimal combination of Rubus
      coreanus and Astragalus membranaceus in 7:3 mixture (RAM) in ovariectomized (OVX)
      mice by investigating bone biomechanical properties and the serum levels of TNF
      alpha, osteocalcin, RANKL, OPG, and RANK-RANKL signal-related osteoclast
      differentiation markers. MATERIALS AND METHODS: A total of 36 mature female
      outbred ICR (Institute of cancer research) strain mice (7 weeks) were divided
      into 6 groups with 7 mice in each group as follows: (1) Sham-operated control
      mice (Sham) received daily oral phosphate-buffered-saline (PBS) of equal volumes
      through gavage. (2) OVX mice received a daily oral gavage of PBS (OVX). (3) OVX
      mice were treated daily with 50mg/kgb.w./day of RAM (4) with 100mg/kgb.w./day of
      RAM or (5) with 200mg/kgb.w./day of RAM via oral gavage. (6) OVX mice received
      i.p. injections of 17beta-estradiol (E2) (0.1mg/kgb.w./day) three times per week
      for 12 weeks. RESULTS: Micro-CT images showed that oral administration of RAM to
      OVX mice prevented tibial bone loss, preserved trabecular bone microarchitecture,
      and improved bone biomechanical properties. RAM administration also showed
      recovery effects on the levels of TNF-alpha, OPG and RANKL concentration in OVX
      states. Additionally, we found that the mechanism by which RAM elicited anti
      osteoporotic effects was by down-regulating the expression of TRAF6 and NFATc1 in
      RANKL-RANK pathway, a route of osteoclast differentiation, followed by reducing
      the production of osteoclast differentiation factors, calcitonin receptors and
      cathepsin K. CONCLUSIONS: Our research strongly suggests that RAM can be
      clinically used in the prevention and treatment of postmenopausal osteoporosis.

PMID- 24333365
TI  - Analysis of the restorative effect of Bu-zhong-yi-qi-tang in the spleen-qi
      deficiency rat model using (1)H-NMR-based metabonomics.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bu-zhong-yi-qi-tang (BT) is a classical formula
      for the treatment of spleen-qi descending, visceroptosis with hyposplenic qi,
      uterine prolapse, and rectal prolapse due to chronic diarrhea in traditional
      Chinese medicine (TCM) and has been identified as an effective drug for the
      treatment of TCM spleen-qi deficiency in clinical practice. The present study
      aimed to investigate the restorative effect and the potential mechanisms of Bu
      zhong-yi-qi-tang in a rat spleen-qi deficiency model using (1)H-NMR-based
      metabonomics. MATERIALS AND METHODS: The rat spleen-qi deficiency model was
      established as follows: oral administration of Radix Rhei extract (equivalent to
      10g/kg body weight of the crude drug), loaded swimming, and starvation for 24h.
      Each of these treatments was administered consecutively every three days. Sixty
      male SD rats were randomly divided into five groups, and three of the groups
      received a different oral dose of the aqueous extract of Bu-zhong-yi-qi-tang
      during the last seven days of the three-week experimental period. The body weight
      and motor behavior of the rats were measured and recorded once a week. The
      endogenous metabolites in the plasma were analyzed using NMR in conjunction with
      multivariate and statistical techniques. In addition, the liver and spleen were
      removed and weighed. RESULTS: All of the rats in the spleen-qi deficiency group
      presented pasty loose stools, inactiveness, grouping, a decrease in swimming
      endurance, and lackluster, loose, and disorderly behavior in addition to a
      significant decrease in body weight, spleen weight, and liver weight. In
      contrast, the abovementioned demonstrations were reversed to a certain extent in
      the rats treated with Bu-zhong-yi-qi-tang compared with the model group (p<0.05,
      p<0.01). A significant separation was determined between the control and model
      groups in the PCA score plot, which indicates that the spleen-qi deficiency model
      was successfully duplicated. The changes in the levels of endogenous metabolites
      in the plasma included lower levels of valine, leucine, and O-acetyl-glycoprotein
      and a higher concentration of lactate in the spleen-qi deficiency group compared
      with the control group. Treatment with Bu-zhong-yi-qi-tang at least partially
      returned the levels of these metabolites to the normal levels. CONCLUSIONS: The
      restorative effects of Bu-zhong-yi-qi-tang in rats with spleen-qi deficiency were
      confirmed, and four endogenous metabolites were identified as potential
      biomarkers of the symptoms of spleen-qi deficiency and most likely play roles in
      the changes observed in certain metabolic pathways, such as the energy, protein,
      and glycolytic metabolisms.

PMID- 24333366
TI  - Headache in childhood and adolescence.

PMID- 24333368
TI  - Treatment options in patients with chylothorax.
AB  - BACKGROUND: Chylothorax arises when lymphatic fluid (chyle) accumulates in the
      pleural cavity because of leakage from lymphatic vessels. It is most commonly
      seen after thoracic surgery (in 0.5% to 1% of cases) and in association with
      tumors. No prospective or randomized trials have yet been performed to evaluate
      the available treatment options. METHOD: This review is based on a selective
      search of the PubMed database for pertinent publications from the years 1995 to
      2013. Emphasis was laid on articles that enabled a comparative assessment of
      treatment options. RESULTS: Initial conservative treatment (e.g., parenteral
      nutrition or a special diet) succeeds in 20% to 80% of cases. When such treatment
      fails, the standard approach up to the present has been to treat surgically,
      e.g., with ligation of the thoracic duct, pleurodesis, or a pleuroperitoneal
      shunt. The success rates of such procedures have ranged from 25% to 95%. Most of
      the patients undergoing such procedures are severely ill; complication rates as
      high as 38% have been reported, with mortality as high as 25%. In more recent
      publications, however, morbidity and mortality were lower. Interventional
      radiological treatments, such as percutaneous thoracic duct embolization or the
      percutaneous destruction of lymphatic vessels, succeed in about 70% of cases and
      lead to healing in up to 80% of cases, even after unsuccessful surgery. The
      complication rate of percutaneous methods is roughly 3%. CONCLUSION:
      Interventional radiological procedures have now taken their place alongside
      conservative treatment and surgery in the management of chylothorax, although
      they are currently available in only a small number of centers.

PMID- 24333369
TI  - Production and characterization of a retinoic acid receptor RARgamma construction
      encompassing the DNA binding domain and the disordered N-terminal proline rich
      domain.
AB  - Gene activation by retinoic acid nuclear receptors (RAR) is regulated by a number
      of molecular events such as ligand binding, interaction with cognate DNA
      sequences and co-regulatory proteins, and phosphorylation. Among the several
      phosphorylation sites that are involved in the non-genomic regulatory pathways of
      the RAR, two are located in a proline rich domain (PRD) within the N-terminal
      domain (NTD) of the receptor. This region is predicted to be intrinsically
      disordered, complicating its production and purification. We present here an
      approach enabling the high yield production of RAR fragments encompassing the PRD
      and the DNA binding domain (DBD). We found that expression levels were dependent
      on where the position of the N-terminal boundary of the fragment was placed
      within the RAR sequence. The purification protocol involves the use of maltose
      binding protein as a solubilising tag and extensive centrifugation steps at
      critical points of the purification process. This protocol is suitable to express
      (15)N, (13)C labeled proteins enabling nuclear magnetic resonance studies. The
      resulting proteins were characterized by biophysical methods including Small
      Angle X-ray Scattering and NMR. These studies showed that PRD extension of
      RARgamma is disordered in solution, a state that is compatible with modifications
      such as phosphorylation. 

PMID- 24333367
TI  - Headache in school children: prevalence and risk factors.
AB  - BACKGROUND: Recurrent headache is a common problem in school children. Evaluation
      generally leads to the diagnosis of a primary headache syndrome (migraine or
      tension-type headache). This review is addressed to the question whether
      headaches in school children are becoming more common and, if so, what risk
      factors are associated with the rise in frequency. METHOD: We selectively
      searched the PubMed database for pertinent publications that contained the terms
      "primary headache AND children/adolescent AND risk factors/prevalence." Articles
      published in either English or German up to April 2013 were considered. Articles
      on secondary types of headache were excluded. RESULTS: Headaches are becoming
      more common among school children. At present, 66% to 71% of 12- to 15- year-olds
      have at least one headache every three months, and 33% to 40% have at least one
      per week. Headache is often accompanied by other physical and/or emotional
      manifestations. Studies from Scandinavia reveal increasing prevalence in age
      groups from 8 years of age and upward. Various studies have identified the
      following risk factors for headache or for its chronification (up to 5.8-fold
      elevation of risk): a dysfunctional family situation, the regular consumption of
      alcohol, caffeine ingestion, smoking, a low level of physical activity, physical
      or emotional abuse, bullying by peers, unfair treatment in school, and
      insufficient leisure time. CONCLUSION: Headaches are becoming more common among
      children and adolescents. They are often associated with other physical and
      emotional complaints.

PMID- 24333370
TI  - Molecular characterization of chicken-derived genotype VIId Newcastle disease
      virus isolates in China during 2005-2012 reveals a new length in hemagglutinin
      neuraminidase.
AB  - Newcastle disease (ND) is one of the most important diseases of poultry, and
      causes severe economic losses in the global poultry industry. Although all
      Newcastle disease virus (NDV) isolates belong to a single serotype, significant
      genetic diversity has been described between different NDV isolates. Here, we
      report the molecular characterization of 23 virulent genotype VIId NDV isolates
      of class II circulating in China. Phylogenetic construction and analysis revealed
      the existence of distinctly genomic and amino acid differences that clearly
      distinguished these isolates from other typical NDV genotypes and vaccine
      strains. We also report a new 582-amino-acid hemagglutinin-neuraminidase in
      genotype VII NDV strains. This is believed to be the first study to investigate
      systematically the most predominant NDV strains, and provides more information on
      the genetic nature of genotype VIId NDV of class II circulating in China. 

PMID- 24333371
TI  - A genome-wide association study identifies major loci affecting the immune
      response against infectious bronchitis virus in chicken.
AB  - Coronaviruses are a hot research topic because they can cause severe diseases in
      humans and animals. Infectious bronchitis virus (IBV), belonging to gamma
      coronaviruses, causes a highly infectious respiratory viral disease and can
      result in catastrophic economic losses to the poultry industry worldwide.
      Unfortunately, the genetic basis of the host immune responses against IBV is
      poorly understood. In the present study, the antibody levels against IBV post
      immunization were measured by an enzyme-linked immunosorbent assay in the serum
      of 511 individuals from a commercial chicken (Gallus gallus) population. A genome
      wide association study using 43,211 single nucleotide polymorphism markers was
      performed to identify the major loci affecting the immune response against IBV.
      This study detected 20 significant (P<1.16 * 10(-6)) effect single nucleotide
      polymorphisms for the antibody level against IBV. These single nucleotide
      polymorphisms were distributed on five chicken chromosomes (GGA), involving GGA1,
      GGA3, GGA5, GGA8, and GGA9. The genes in the 1-Mb windows surrounding each single
      nucleotide polymorphism with significant effect for the antibody level against
      IBV were associated with many biological processes or pathways related to
      immunity, such as the defense response and mTOR signaling pathway. A genomic
      region containing a cluster of 13 beta-defensin (GAL1-13) and interleukin-17F
      genes on GGA3 probably plays an important role in the immune response against
      IBV. In addition, the major loci significantly associated with the antibody level
      against IBV on GGA1 and GGA5 could explain about 12% and 13% of the phenotypic
      variation, respectively. This study suggested that the chicken genome has several
      important loci affecting the immune response against IBV, and increases our
      knowledge of how to control outbreaks of infectious bronchitis.

PMID- 24333372
TI  - Comparative analysis of microRNAs from the lungs and trachea of dogs (Canis
      familiaris) infected with canine influenza virus.
AB  - MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs of 18-22
      nucleotides in length that regulate gene expression at the post-transcriptional
      level. The objective of this study was to examine the differences in the miRNA
      expression profiles of the lungs and trachea of beagle dogs infected with canine
      influenza virus (CIV). Total RNA was isolated from lung and trachea tissues of
      beagle dogs infected and non-infected with H3N2 CIV at 4 dpi. A total of
      41,512,315 and 39,107,475 reads were obtained from the lung and trachea,
      respectively. Out of a total 288 dog miRNAs available in miRBase, 227 and 236
      miRNAs were detected in the infected (Fg) and the non-infected lungs (Fc),
      respectively, whereas 242 miRNAs were detected in both the infected (Qg) and the
      non-infected trachea (Qc). From these, 34 and 45 miRNAs were differentially
      expressed in the lungs and trachea between the infected and non-infected dogs,
      respectively. More miRNAs were highly expressed in the non-infected tissues than
      in the infected tissues. miR-143 was the most abundantly expressed miRNA in the
      four samples, followed by let-7. In total, 252, 234, 196 and 235 novel miRNAs
      were identified in the Fc, Fg, Qc, and Qg groups, respectively. To our knowledge,
      this is the first study examining the miRNA gene expression in CIV infected dogs
      using the Solexa sequencing approach. We have revealed the existence of a large
      number miRNAs that are affected by CIV infection as well as identified some
      potentially new miRNAs. These findings will help us better understand the host
      CIV interaction and its relationship to pathogenesis, as well as contribute to
      the prevention and control of CIV.

PMID- 24333373
TI  - Development and characterization of nano-fiber patch for the treatment of
      glaucoma.
AB  - In the present work polymeric nano-fiber patches was developed for the effective
      treatment of glaucoma using timolol maleate and dorzolamide hydrochloride as
      model drugs. The nano-fibers were prepared by electrospinning technique and were
      characterized on the basis of fiber diameter, morphology, entrapment efficiency,
      mucoadhesive strength, and drug release behavior, etc. Final formulations were
      inserted in the cul-de-sac of glaucoma induced rabbits and the efficacy of the
      formulation was evaluated. The results clearly indicated the potential of the
      developed formulation for occur drug delivery. There was a significant fall in
      the intraocular pressure compared to commercial eye drops. 

PMID- 24333375
TI  - Effects of chemokine receptor signalling on cognition-like, emotion-like and
      sociability behaviours of CCR6 and CCR7 knockout mice.
AB  - Inflammation is regarded as an important mechanism of neuropsychiatric disorders.
      Chemokines, which are a part of the immune system, have effects on various
      aspects of brain function, but little is known about their effects on behaviour.
      We have compared the cognition-like behaviour (learning and spatial memory) of
      CCR6(-/-) and CCR7(-/-) mice with wild type (WT) C57BL/6 mice, in the Barnes
      maze, as well as a range of other behaviours, including exploratory, anxiety and
      depression-like behaviour, using a battery of tests. Levels of cytokines TNF
      alpha, IL-1beta and IL-6 were also measured. In the Barnes maze, CCR7(-/-) mice
      were shown to take longer to learn the location of the escape box on the 1st of 4
      days of training. In the behavioural battery, CCR6(-/-) mice showed higher
      locomotor activity and lower anxiety in the open field test, and a lack of
      preference for social novelty in a sociability test. CCR7(-/-) mice behaved much
      like WT mice, although showed higher anxiety in Elevated Zero Maze. While
      baseline saccharin preference in a 2-bottle choice test, a test for anhedonia
      depression-like behaviour, was equal in all strains at baseline, weekly tests
      showed that both CCR6(-/-) and CCR7(-/-) mice developed a decreased preference
      for saccharin compared to WT over time. There were no differences between strains
      in any of the cytokines measured. These results suggest that chemokine receptors
      may play a role in cognition and learning behaviour, as well as anxiety and other
      behaviours, although the biological mechanisms are still unclear. 

PMID- 24333374
TI  - Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters.
AB  - Emotional behaviors are influenced by the circadian timing system. Circadian
      disruptions are associated with depressive-like symptoms in clinical and
      preclinical populations. Circadian rhythm robustness declines markedly with aging
      and may contribute to susceptibility to emotional dysregulation in aged
      individuals. The present experiments used a model of chronic circadian arrhythmia
      generated noninvasively, via a series of circadian-disruptive light treatments,
      to investigate interactions between circadian desynchrony and aging on depressive
      and anxiety-like behaviors, and on limbic neuroinflammatory gene expression that
      has been linked with emotionality. We also examined whether a social manipulation
      (group housing) would attenuate effects of arrhythmia on emotionality. In aged
      (14-18 months of age) male Siberian hamsters, circadian arrhythmia increased
      behavioral despair and decreased social motivation, but decreased exploratory
      anxiety. These effects were not evident in younger (5-9 months of age) hamsters.
      Social housing (3-5 hamsters/cage) abolished the effects of circadian arrhythmia
      on emotionality. Circadian arrhythmia alone was without effect on hippocampal or
      cortical interleukin-1beta (IL-1beta) and indoleamine 2,3-dioxygenase (Ido) mRNA
      expression in aged hamsters, but social housing decreased hippocampal IL-1beta
      and Ido mRNAs. The data demonstrate that circadian disruption can negatively
      impact affective state, and that this effect is pronounced in older individuals.
      Although clear associations between circadian arrhythmia and constitutive limbic
      proinflammatory activity were not evident, the present data suggest that social
      housing markedly inhibits constitutive hippocampal IL-1beta and Ido activity,
      which may contribute to the ameliorating effects of social housing on a number of
      emotional behaviors. 

PMID- 24333376
TI  - Repeated nicotine exposure during adolescence alters reward-related learning in
      male and female rats.
AB  - RATIONALE: Repeated nicotine exposure causes neuroadaptations in limbic cortico
      striatal circuits involved in learning and motivation. Such alterations are
      relevant to addiction because they are suggested to mediate the ability of
      smoking-associated stimuli to control behavior and to enhance nicotine-seeking
      and -taking behaviors. Female smokers report higher cue reactivity relative to
      their male counter parts, yet little is known about putative gender-specific
      effects of adolescent nicotine exposure on reward-related learning. Prior
      repeated nicotine exposure in adult male rats enhances Pavlovian approach
      behavior and conditioned reinforcement. OBJECTIVE: Given that smoking is
      typically initiated during adolescence, here we assessed the extent to which
      adolescent nicotine exposure impacts Pavlovian approach and conditioned
      reinforcement in male and female rats. METHODS: Rats were injected with nicotine
      on postnatal days 31-45 prior to training on Pavlovian approach behavior starting
      on day 51. They were trained to associate a conditioned stimulus (CS),
      illumination of a magazine light, and tone, with an unconditioned stimulus (US),
      the delivery of water, for 10-daily sessions, and then were tested on the
      acquisition of responding with conditioned reinforcement. RESULTS: Adolescent
      nicotine exposure selectively increased approach to the magazine during the CS in
      males but decreased approach to the magazine during the CS in female rats.
      Vehicle-exposed female rats, however, showed greater magazine approach during the
      CS than did male control rats. Prior nicotine exposure also enhanced conditioned
      reinforcement in both male and female rats. CONCLUSIONS: Repeated exposure to
      nicotine during adolescence had opposite effects on Pavlovian approach behavior
      in male and female rats but enhanced acquisition of a new response with
      conditioned reinforcement. Novel information on how nicotine exposure influences
      reward-related learning during adolescence may increase our understanding of
      neurobiological mechanisms involved in the initiation of smoking behavior.

PMID- 24333378
TI  - Effects of thalamic lesions on repeated relearning of a spatial working memory
      task.
AB  - Anterior thalamic (ATN) dysfunction produces memory deficits in rats and humans.
      The current study shows that, with a substantial delay between post-surgery
      tests, controls show repeated relearning on a spatial working memory task whereas
      rats with neurotoxic ATN lesions showed repeated relearning deficits. Rats were
      pre-trained to criterion, but not over trained, on the spatial task. ATN lesions
      produced the expected spatial memory and relearning deficits about two weeks post
      surgery and again either one or 15 weeks later. Control rats also showed
      forgetting post-surgery and after a 15 week break, relearning the task on each
      occasion. Controls with only a 1 week break before their final re-test showed
      negligible forgetting. Thus, a short break between re-tests replicated previous
      findings with ATN lesions, but a long break allows repeated comparison of rates
      of learning from a common starting point in sham and ATN-lesioned animals,
      providing a useful paradigm for future testing of pro-cognitive treatments. 

PMID- 24333377
TI  - Sleep deprivation impairs performance in the 5-choice continuous performance
      test: similarities between humans and mice.
AB  - Several groups undergo extended periods without sleep due to working conditions
      or mental illness. Such sleep deprivation (SD) can deleteriously affect
      attentional processes and disrupt work and family functioning. Understanding the
      biological underpinnings of SD effects may assist in developing sleep therapies
      and cognitive enhancers. Utilizing cross-species tests of attentional processing
      in humans and rodents would aid in mechanistic studies examining SD-induced
      inattention. We assessed the effects of 36h of: (1) Total SD (TSD) in healthy
      male and female humans (n=50); and (2) REM SD (RSD) in male C57BL/6 mice (n=26)
      on performance in the cross-species 5-choice continuous performance test (5C
      CPT). The 5C-CPT includes target trials on which subjects were required to
      respond and non-target trials on which subjects were required to inhibit from
      responding. TSD-induced effects on human psychomotor vigilance test (PVT) were
      also examined. Effects of SD were also examined on mice split into good and poor
      performance groups based on pre-deprivation scores. In the human 5C-CPT, TSD
      decreased hit rate and vigilance with trend-level effects on accuracy. In the
      PVT, TSD slowed response times and increased lapses. In the mouse 5C-CPT, RSD
      reduced accuracy and hit rate with trend-level effects on vigilance, primarily in
      good performers. In conclusion, SD induced impaired 5C-CPT performance in both
      humans and mice and validates the 5C-CPT as a cross-species translational task.
      The 5C-CPT can be used to examine mechanisms underlying SD-induced deficits in
      vigilance and assist in testing putative cognitive enhancers. 

PMID- 24333379
TI  - Impaired suppression of feeding by the gut hormone xenin in type I interleukin-1
      receptor-deficient mice.
AB  - Xenin is a gut hormone that reduces food intake partly by acting through the
      hypothalamus. However, the mechanism of hypothalamic xenin action is not fully
      understood. To identify xenin-regulated genes in the hypothalamus, we compared
      expression levels of metabolism-related genes in the hypothalamus between saline
      treated control and xenin-treated mice. Intraperitoneal injection of xenin caused
      a significant increase in hypothalamic interleukin 1 beta (IL-1beta) mRNA levels
      without causing a significant change in hypothalamic IL-1alpha mRNA levels. To
      further examine the possible contribution of IL-1 signaling to xenin's
      anorexigenic action, the effect of intraperitoneal injection of xenin on food
      intake was compared between wild-type and type I IL-1 receptor (IL-1RI)-deficient
      mice. Intraperitoneal administration of xenin (7.5 MUg/g b.w.) caused a
      significant reduction of food intake in wild-type mice, while it failed to reduce
      food intake in pre-obese IL-1RI-deficient mice. These findings support the role
      of hypothalamic IL-1beta-IL-1RI signaling in the mediation of the anorexigenic
      effect of xenin.

PMID- 24333381
TI  - Something to talk about: enhancement of linguistic cohesion through tdCS in
      chronic non fluent aphasia.
AB  - Several studies have shown that the modulation of cortical activity through
      transcranial direct current stimulation (tDCS) enhances naming performance in
      persons with aphasia. In this study, we investigated the potential effects of
      tDCS in improving spontaneous speech and the ability to use connective words to
      establish cohesion among adjacent utterances in a group of eight participants
      with chronic non fluent aphasia. They were administered five short videoclips
      representing everyday life contexts and two picture description tasks. Three
      videoclips were used to elicit spontaneous conversation during the treatment,
      while the remaining tasks were presented to the patients only before and after
      the therapy. Patients were required to talk about each videoclip, with the help
      of a therapist, while they were treated with tDCS (20 min, 1 mA) over the left
      hemisphere in three different conditions: anodic tDCS over the Broca's area,
      anodic tDCS over the Wernicke's area and a sham condition. Each experimental
      condition was performed for ten consecutive daily sessions with 14 days of
      intersession interval. Only after Broca's stimulation, patients showed a greater
      improvement in producing words that enhanced the cohesion of their speech samples
      (i.e., pronouns, ellipses, word repetitions, conjunctions). Beneficial effects of
      the stimulation were generalized also to contexts presented to the patients at
      the beginning and at the end of the therapy sessions. Our data further confirm
      the key role of the left inferior frontal gyrus in binding words into a coherent
      speech. We believe that positive tDCS effects may be further extended to
      different linguistic domains, useful to promote language recovery.

PMID- 24333380
TI  - Dopamine is differentially involved in the locomotor hyperactivity produced by
      manipulations of opioid, GABA and glutamate receptors in the median raphe
      nucleus.
AB  - The median raphe nucleus (MR) has been shown to exert a powerful influence on
      behavioral arousal and marked locomotor hyperactivity can be produced by intra-MR
      injections of a variety of drugs including GABAA and GABAB agonists, excitatory
      amino acid antagonists, and MU- and delta-opioid agonists. Other studies have
      indicated that the MR exerts an inhibitory influence on ascending dopamine
      systems, suggesting that MR induced alterations in activity may be mediated
      through changes in dopaminergic transmission. In the present study, we explored
      this possibility by examining whether systemic administration of the preferential
      D2 dopamine antagonist haloperidol is able to antagonize the hyperactivity
      produced by intra-MR injections of various drugs. We found that haloperidol
      completely blocked the locomotor response to intra-MR injections of the MU-opioid
      receptor agonist DAMGO and the delta-opioid receptor agonist DPDPE. In marked
      contrast, at doses which abolished the locomotor response to systemic
      amphetamine, haloperidol had no effect on the hyperactivity induced by intra-MR
      injections of GABAA agonist muscimol, the GABAB agonist baclofen, or the
      kainate/quisqualate antagonist pBB-PZDA, even though it suppressed baseline
      activity in these same animals. These results indicate that there must be at
      least two mechanisms capable of influencing behavioral arousal within the MR
      region, one of which is dependent on D2 dopamine receptors and the other is not. 

PMID- 24333383
TI  - Prefrontal tetanic stimulation, following fear reconditioning, facilitates
      expression of previously acquired extinction.
AB  - We have recently shown that post-extinction retraining of rats, with a shock
      intensity that is too weak to induce by itself significant fear acquisition,
      impairs the recall of fear extinction memory. Tetanic stimulation (TS) of the
      medial prefrontal cortex (mPFC), applied before or following this retraining,
      facilitates extinction recall. Here we investigated whether mPFC TS can also
      facilitate expression of fear extinction when rats are retrained with the same
      shock intensity as during the initial fear acquisition. Rats were implanted with
      stimulating electrodes in the mPFC and were trained to acquire freezing to a
      conditioning chamber, in which they had to enter freely. In Experiment 1,
      extinction of this response was followed by reconditioning and then another
      extinction training. Acquired freezing was extinguished successfully, while
      reacquired freezing, which was associated with increased chamber entry latencies,
      was resistant to subsequent extinction. Both reacquired freezing and increased
      chamber entry latencies were absent in rats that received post-reconditioning
      mPFC TS. In Experiment 2, post-conditioning mPFC TS had no effect on initially
      acquired freezing. In Experiment 3, rats were submitted to reconditioning without
      experiencing extinction training. In this condition, both reacquired freezing and
      increased chamber entry latencies were still present in rats that received post
      reconditioning mPFC TS. These findings provide additional evidence for the
      fundamental role of the mPFC in maintaining expression of fear extinction. 

PMID- 24333382
TI  - Membrane attachment and structure models of lipid storage droplet protein 1.
AB  - Neutral lipid triglycerides, a main reserve for fat and energy, are stored in
      organelles called lipid droplets. The storage and release of triglycerides are
      actively regulated by several proteins specific to the droplet surface, one of
      which in insects is PLIN1. PLIN1 plays a key role in the activation of
      triglyceride hydrolysis upon phosphorylation. However, the structure of PLIN1 and
      its relation to functions remain elusive due to its insolubility and
      crystallization difficulty. Here we report the first solid-state NMR study on the
      Drosophila melanogaster PLIN1 in combination with molecular dynamics simulation
      to show the structural basis for its lipid droplet attachment. NMR spin diffusion
      experiments were consistent with the predicted membrane attachment motif of
      PLIN1. The data indicated that PLIN1 has close contact with the terminal methyl
      groups of the phospholipid acyl chains. Structure models for the membrane
      attachment motif were generated based on hydrophobicity analysis and NMR membrane
      insertion depth information. Simulated NMR spectra from a trans-model agreed with
      experimental spectra. In this model, lipids from the bottom leaflet were very
      close to the surface in the region enclosed by membrane attachment motif. This
      may imply that in real lipid droplet, triglyceride molecules might be brought
      close to the surface by the same mechanism, ready to leave the droplet in the
      event of lipolysis. Juxtaposition of triglyceride lipase structure to the trans
      model suggested a possible interaction of a conserved segment with the lipase by
      electrostatic interactions, opening the lipase lid to expose the catalytic
      center. 

PMID- 24333384
TI  - Many inflammatory bowel disease risk loci include regions that regulate gene
      expression in immune cells and the intestinal epithelium.
AB  - BACKGROUND & AIMS: The contribution of genetic factors to the pathogenesis of
      inflammatory bowel disease (IBD) has been established by twin, targeted
      sequencing, and genome-wide association studies. These studies identified many
      risk loci, and research is underway to identify causal variants. These studies
      have focused mainly on protein-coding genes. We investigated other functional
      elements in the human genome, such as regulatory regions. METHODS: Using
      acetylated histone 3 lysine 27 chromatin immunoprecipitation and sequencing, we
      identified tens of thousands of potential regulatory regions that are active in
      intestinal epithelium (primary intestinal crypts and cultured organoids) isolated
      from resected material and from biopsies collected during ileo-colonoscopies and
      immune cells (monocytes, macrophages, CD34(+), CD4(+), and CD8(+)). We correlated
      these regions with susceptibility loci for IBD. RESULTS: We have generated
      acetylated histone 3 lysine 27 profiles from primary intestinal epithelium and
      cultured organoids, which we have made publically available. We found that 45 of
      163 single nucleotide polymorphisms (SNPs) associated with IBD overlap
      specifically with active regulatory elements. In addition, by taking strong
      linkage disequilibrium into account, another 47 IBD-associated SNPs colocalized
      with active regulatory elements through other SNPs in their vicinity. Altogether,
      92 of 163 IBD-associated SNPs correlated with distinct active regulatory elements
      a frequency 2.5- to 3.5-fold greater than that expected from random sampling. The
      variations in these SNPs often create or disrupt known binding motifs; they might
      affect the binding of transcriptional regulators to alter expression of regulated
      genes. CONCLUSIONS: In addition to variants in protein coding genes, variants in
      noncoding DNA regulatory regions that are active in intestinal epithelium and
      immune cells are potentially involved in the pathogenesis of IBD.

PMID- 24333385
TI  - Hierarchical organization and structural flexibility of thylakoid membranes.
AB  - Chloroplast thylakoid membranes accommodate densely packed protein complexes in
      ordered, often semi-crystalline arrays and are assembled into highly organized
      multilamellar systems, an organization warranting a substantial degree of
      stability. At the same time, they exhibit remarkable structural flexibility,
      which appears to play important - yet not fully understood - roles in different
      short-term adaptation mechanisms in response to rapidly changing environmental
      conditions. In this review I will focus on dynamic features of the hierarchically
      organized photosynthetic machineries at different levels of structural
      complexity: (i) isolated light harvesting complexes, (ii) molecular
      macroassemblies and supercomplexes, (iii) thylakoid membranes and (iv) their
      multilamellar membrane systems. Special attention will be paid to the most
      abundant systems, the major light harvesting antenna complex, LHCII, and to
      grana. Two physical mechanisms, which are less frequently treated in the
      literature, will receive special attention: (i) thermo-optic mechanism 
      elementary structural changes elicited by ultrafast local heat transients due to
      the dissipation of photon energy, which operates both in isolated antenna
      assemblies and the native thylakoid membranes, regulates important enzymatic
      functions and appears to play role in light adaptation and photoprotection
      mechanisms; and (ii) the mechanism by which non-bilayer lipids and lipid phases
      play key role in the functioning of xanthophyll cycle de-epoxidases and are
      proposed to regulate the protein-to-lipid ratio in thylakoid membranes and
      contribute to membrane dynamics. This article is part of a Special Issue
      entitled: Dynamic and ultrastructure of bioenergetic membranes and their
      components. 

PMID- 24333386
TI  - Action spectra of photosystems II and I and quantum yield of photosynthesis in
      leaves in State 1.
AB  - The spectral global quantum yield (YII, electrons/photons absorbed) of
      photosystem II (PSII) was measured in sunflower leaves in State 1 using
      monochromatic light. The global quantum yield of PSI (YI) was measured using low
      intensity monochromatic light flashes and the associated transmittance change at
      810nm. The 810-nm signal change was calibrated based on the number of electrons
      generated by PSII during the flash (4.O2 evolution) which arrived at the PSI
      donor side after a delay of 2ms. The intrinsic quantum yield of PSI (yI,
      electrons per photon absorbed by PSI) was measured at 712nm, where photon
      absorption by PSII was small. The results were used to resolve the individual
      spectra of the excitation partitioning coefficients between PSI (aI) and PSII
      (aII) in leaves. For comparison, pigment-protein complexes for PSII and PSI were
      isolated, separated by sucrose density ultracentrifugation, and their optical
      density was measured. A good correlation was obtained for the spectral excitation
      partitioning coefficients measured by these different methods. The intrinsic
      yield of PSI was high (yI=0.88), but it absorbed only about 1/3 of quanta;
      consequently, about 2/3 of quanta were absorbed by PSII, but processed with the
      low intrinsic yield yII=0.63. In PSII, the quantum yield of charge separation was
      0.89 as detected by variable fluorescence Fv/Fm, but 29% of separated charges
      recombined (Laisk A, Eichelmann H and Oja V, Photosynth. Res. 113, 145-155). At
      wavelengths less than 580nm about 30% of excitation is absorbed by pigments
      poorly connected to either photosystem, most likely carotenoids bound in pigment
      protein complexes. 

PMID- 24333387
TI  - Glial activation and post-synaptic neurotoxicity: the key events in
      Streptozotocin (ICV) induced memory impairment in rats.
AB  - In the present study the role of glial activation and post synaptic toxicity in
      ICV Streptozotocin (STZ) induced memory impaired rats was explored. In experiment
      set up 1: Memory deficit was found in Morris water maze test on 14-16 days after
      STZ (ICV; 3mg/Kg) administration. STZ causes increased expression of GFAP, CD11b
      and TNF-alpha indicating glial activation and neuroinflammation. STZ also
      significantly increased the level of ROS, nitrite, Ca(2+) and reduced the
      mitochondrial activity in synaptosomal preparation illustrating free radical
      generation and excitotoxicity. Increased expression and activity of Caspase-3 was
      also observed in STZ treated rat which specify apoptotic cell death in
      hippocampus and cortex. STZ treatment showed decrease expression of post synaptic
      markers CaMKIIalpha and PSD-95, while, expression of pre synaptic markers
      (synaptophysin and SNAP-25) remains unaltered indicating selective post synaptic
      neurotoxicity. Oral treatment with Memantine (10mg/kg) and Ibuprofen (50 mg/kg)
      daily for 13 days attenuated STZ induced glial activation, apoptotic cell death
      and post synaptic neurotoxicity in rat brain. Further, in experiment set up 2:
      where memory function was not affected i.e. 7-9 days after STZ treatment. The
      level of GFAP, CD11b, TNF-alpha, ROS and nitrite levels were increased. On the
      other hand, apoptotic marker, synaptic markers, mitochondrial activity and Ca(2+)
      levels remained unaffected. Collective data indicates that neuroinflammatory
      process and oxidative stress occurs earlier to apoptosis and does not affect
      memory function. Present study clearly suggests that glial activation and post
      synaptic neurotoxicity are the key factors in STZ induced memory impairment and
      neuronal cell death.

PMID- 24333388
TI  - Antinociceptive actions of peripheral glucose administration.
AB  - The effects of intraperitoneal (ip) D-glucose administration on antinociception
      were studied in male Long-Evans rats. Rats were assessed for antinociception
      using the hot-water tail-withdrawal procedure (54+/-0.2  degrees C) to determine
      if peripheral administration of D-glucose (300, 560, or 720 mg/kg) would enhance
      morphine-mediated antinociception (MMA) (1.0, 3.0, 4.2, 5.6, and 10.0mg/kg
      cumulative-dosing regime) and if D-glucose (560, 720, or 1000 mg/kg) alone could
      produce antinociceptive activity that was naloxone (0.32 mg/kg) reversible.
      Additionally, the actions of D-glucose on MMA were compared with a stereoisomer,
      L-glucose, which is not metabolized. The results of these studies demonstrate
      that peripheral administration of D-glucose significantly enhances MMA and that D
      glucose alone produces antinociceptive actions that are potentially mediated by
      the endogenous opioid system. Furthermore, L-glucose failed to have an effect on
      MMA suggesting that the alterations in antinociception seen with D-glucose are
      not due to stressors such as osmolality or injection. The current studies provide
      evidence that D-glucose alteration of antinociception is not simply a response to
      taste or gustation.

PMID- 24333390
TI  - HDL-cholesterol in coronary artery disease risk: function or structure?
AB  - High-density lipoproteins (HDL) are inversely related with coronary artery
      disease (CAD) and HDL-cholesterol is the only standardized and reproducible
      parameter available to estimate plasma concentration of these lipoproteins.
      However, pharmacological interventions intended to increase HDL-cholesterol have
      not been consistently associated to an effective CAD risk reduction. Among
      patients with a myocardial infarction, 43 and 44% of men and women, respectively,
      had normal plasma levels of HDL-cholesterol, whereas genetic studies have failed
      to show a causal association between HDL-cholesterol and CAD risk. Instead, HDL
      functionality seems to be the target to be evaluated, but the existing methods
      are still poorly reproducible and far to be adapted to the clinical laboratory.
      HDL subclasses rise as a potential alternative for the evaluation of CAD risk;
      HDL subclasses are a surrogate of intravascular metabolism of these lipoproteins
      and probably of their functionality. Low levels of large HDL and increased
      proportions of small particles are the most remarkable features associated to an
      increased risk of type 2 diabetes mellitus (T2DM) or CAD. However, inflammation
      and other environmental factors are related with abnormal HDL structure, and, as
      a consequence, more prospective studies are needed to better support the clinical
      usefulness of HDL subclasses. New insights from proteome and lipidome profiles of
      HDL will provide potential HDL-related biomarkers in the coming years. 

PMID- 24333389
TI  - Relevance of MIA and S100 serum tumor markers to monitor BRAF inhibitor therapy
      in metastatic melanoma patients.
AB  - BRAF V600 mutation has been reported in more than 50% of melanoma cases and its
      presence predicts clinical activity of BRAF inhibitors (iBRAF). We evaluated the
      role of MIA, S100 and LDH to monitor iBRAF efficiency in advanced melanoma
      patients presenting BRAF V600 mutations. This was a prospective study of melanoma
      patients harboring the BRAF V600 mutation and treated with iBRAF within a
      clinical trial (dabrafenib) or as part of an expanded access program
      (vemurafenib). MIA, S100 and LDH were analyzed in serum at baseline, and every 4
      6 weeks during treatment. Eighteen patients with melanoma stages IIIc-IV were
      enrolled with 88.8% of response rate to iBRAF. Baseline concentrations of all the
      tumor markers correlated with tumor burden. MIA and S100 concentrations decreased
      significantly one month after the beginning of treatment and, upon progression,
      their concentrations increased significantly above the minimum levels previously
      achieved. MIA levels lower than 9 MUg/L one month after the beginning of
      treatment and S100 concentrations lower than 0.1 MUg/L at the moment of best
      response were associated with improved progression-free survival. In conclusion,
      MIA and S100 are useful to monitor response in melanoma patients treated with
      iBRAF.

PMID- 24333391
TI  - Inflammatory and fibrotic proteins proteomically identified as key protein
      constituents in urine and stone matrix of patients with kidney calculi.
AB  - To uncover whether urinary proteins are incorporated into stones, the proteomic
      profiles of kidney stones and urine collected from the same patients have to be
      explored. We employed 1D-PAGE and nanoHPLC-ESI-MS/MS to analyze the proteomes of
      kidney stone matrix (n=16), nephrolithiatic urine (n=14) and healthy urine (n=3).
      We identified 62, 66 and 22 proteins in stone matrix, nephrolithiatic urine and
      healthy urine, respectively. Inflammation- and fibrosis-associated proteins were
      frequently detected in the stone matrix and nephrolithiatic urine. Eighteen
      proteins were exclusively found in the stone matrix and nephrolithiatic urine,
      considered as candidate biomarkers for kidney stone formation. S100A8 and
      fibronectin, representatives of inflammation and fibrosis, respectively, were up
      regulated in nephrolithiasis renal tissues. S100A8 was strongly expressed in
      infiltrated leukocytes. Fibronectin was over-expressed in renal tubular cells.
      S100A8 and fibronectin were immunologically confirmed to exist in nephrolithiatic
      urine and stone matrix, but in healthy urine they were undetectable. Conclusion,
      both kidney stones and urine obtained from the same patients greatly contained
      inflammatory and fibrotic proteins. S100A8 and fibronectin were up-regulated in
      stone-baring kidneys and nephrolithiatic urine. Therefore, inflammation and
      fibrosis are suggested to be involved in the formation of kidney calculi. 

PMID- 24333392
TI  - Use of hydroxypropyl-beta-cyclodextrin/polyethylene glycol 400, modified Fe3O4
      nanoparticles for congo red removal.
AB  - Fe3O4 nanoparticles were modified with Hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) and Polyethylene glycol 400 (PEG400) by a facile one-pot homogeneous
      precipitation method, and were used as a novel nano-adsorbent for the removal of
      congo red (CR) from aqueous solutions. The polymer-modified composites were
      characterized by FTIR, TEM, TGA, XRD and VSM, and showed excellent adsorption
      efficiency for CR. The value of the maximum adsorption capacity calculated
      according to the Langmuir isotherm model were 1.895g/g, which are much high and
      about 19 times that of Fe3O4 nanoparticles. Desorption study further indicates
      the good regeneration ability of the nanocomposites. The results suggest that the
      HP-beta-CD/PEG400-modified Fe3O4 nanoparticles is a promising adsorbent for CR
      removal from aqueous solutions, and it is easily recycled owing to its large
      specific surface area and unique magnetic responsiveness. 

PMID- 24333393
TI  - Network connectivity modulates power spectrum scale invariance.
AB  - Measures of complexity are sensitive in detecting disease, which has made them
      attractive candidates for diagnostic biomarkers; one complexity measure that has
      shown promise in fMRI is power spectrum scale invariance (PSSI). Even if scale
      free features of neuroimaging turn out to be diagnostically useful, however,
      their underlying neurobiological basis is poorly understood. Using modeling and
      simulations of a schematic prefrontal-limbic meso-circuit, with excitatory and
      inhibitory networks of nodes, we present here a framework for how network density
      within a control system can affect the complexity of signal outputs. Our model
      demonstrates that scale-free behavior, similar to that observed in fMRI PSSI
      data, can be obtained for sufficiently large networks in a context as simple as a
      linear stochastic system of differential equations, although the scale-free range
      improves when introducing more realistic, nonlinear behavior in the system. PSSI
      values (reflective of complexity) vary as a function of both input type
      (excitatory, inhibitory) and input density (mean number of long-range
      connections, or strength), independent of their node-specific geometric
      distribution. Signals show pink noise (1/f) behavior when excitatory and
      inhibitory influences are balanced. As excitatory inputs are increased and
      decreased, signals shift towards white and brown noise, respectively. As
      inhibitory inputs are increased and decreased, signals shift towards brown and
      white noise, respectively. The results hold qualitatively at the hemodynamic
      scale, which we modeled by introducing a neurovascular component. Comparing
      hemodynamic simulation results to fMRI PSSI results from 96 individuals across a
      wide spectrum of anxiety-levels, we show how our model can generate concrete and
      testable hypotheses for understanding how connectivity affects regulation of meso
      circuits in the brain. 

PMID- 24333394
TI  - Improved longitudinal gray and white matter atrophy assessment via application of
      a 4-dimensional hidden Markov random field model.
AB  - SIENA and similar techniques have demonstrated the utility of performing "direct"
      measurements as opposed to post-hoc comparison of cross-sectional data for the
      measurement of whole brain (WB) atrophy over time. However, gray matter (GM) and
      white matter (WM) atrophy are now widely recognized as important components of
      neurological disease progression, and are being actively evaluated as secondary
      endpoints in clinical trials. Direct measures of GM/WM change with advantages
      similar to SIENA have been lacking. We created a robust and easily-implemented
      method for direct longitudinal analysis of GM/WM atrophy, SIENAX multi-time-point
      (SIENAX-MTP). We built on the basic halfway-registration and mask composition
      components of SIENA to improve the raw output of FMRIB's FAST tissue segmentation
      tool. In addition, we created LFAST, a modified version of FAST incorporating a
      4th dimension in its hidden Markov random field model in order to directly
      represent time. The method was validated by scan-rescan, simulation, comparison
      with SIENA, and two clinical effect size comparisons. All validation approaches
      demonstrated improved longitudinal precision with the proposed SIENAX-MTP method
      compared to SIENAX. For GM, simulation showed better correlation with
      experimental volume changes (r=0.992 vs. 0.941), scan-rescan showed lower
      standard deviations (3.8% vs. 8.4%), correlation with SIENA was more robust
      (r=0.70 vs. 0.53), and effect sizes were improved by up to 68%. Statistical power
      estimates indicated a potential drop of 55% in the number of subjects required to
      detect the same treatment effect with SIENAX-MTP vs. SIENAX. The proposed direct
      GM/WM method significantly improves on the standard SIENAX technique by trading a
      small amount of bias for a large reduction in variance, and may provide more
      precise data and additional statistical power in longitudinal studies. 

PMID- 24333395
TI  - Bayesian estimation of ERP components from multicondition and multichannel EEG.
AB  - Extraction and separation of functionally different event-related potentials
      (ERPs) from electroencephalography (EEG) is a long-standing problem in cognitive
      neuroscience. In this paper, we propose a Bayesian spatio-temporal model for
      estimating ERP components from multichannel EEG recorded under multiple
      experimental conditions. The model isolates the spatially and temporally
      overlapping ERP components by utilizing their phase-locking structure and the
      inter-condition non-stationarity structure of their amplitudes and latencies.
      Critically, unlike in previous multilinear algorithms, the non-phase-locked
      background EEGs are modeled as spatially correlated and non-isotropic signals. A
      variational algorithm was developed for approximate Bayesian inference of the
      proposed model, with the effective number of ERP components automatically
      determined as a part of the algorithm. The utility of the algorithm is
      demonstrated with applications to synthetic data and the EEG data collected from
      13 subjects during a face inversion experiment. The results show that our
      algorithm more accurately and reliably estimates the spatio-temporal patterns,
      amplitudes, and latencies of the underlying ERP components in comparison with
      several state-of-the-art algorithms. 

PMID- 24333396
TI  - Individuating the neural bases for the recognition of conspecifics with MVPA.
AB  - Conspecifics are potential mates, and can be the most dangerous threats. With
      conspecifics we engage in complex social interactions. Therefore, it is important
      to rapidly detect the presence of conspecifics in a scene. Images of humans
      attract attention, and do so already in 9-months-old infants, showing that the
      distinction between conspecifics and other animals emerges early in development.
      However, despite a wealth of evidence on the behavioral differences between the
      processing of conspecifics and other animals, the neural mechanisms that underlie
      the recognition of conspecifics remain unknown. In this experiment, we used
      recursive feature elimination to individuate brain regions that show selective
      effects for the faces of conspecifics, individuating reliable conspecific effects
      in the right ventrolateral prefrontal cortex (vlPFC). Consistent with the
      importance of conspecifics recognition for reorienting attention and for social
      cognition, this region shows functional connectivity with the temporo-parietal
      junction (TPJ), implicated in reorienting attention and in the attribution of
      mental states to others. Our results suggest that the right vlPFC plays an
      important role for the recognition of conspecifics and may function as a gateway
      for the attribution of mental states to an object. 

PMID- 24333398
TI  - 1,3-Dichloro-2-propanol induced hyperlipidemia in C57BL/6J mice via AMPK
      signaling pathway.
AB  - 1,3-Dichloro-2-propanol (1,3-DCP) is a well-known contaminant that has been
      detected in a wide range of foods. Dietary intake represents the greatest source
      of exposure to 1,3-DCP. In the study, we first found 1,3-DCP could induce
      hyperlipidemia in C57BL/6J mice below 1 mg/kg/day. We investigated serum lipid
      profile, liver total cholesterol (TC) and triglyceride (TG), histopathology of
      Liver and adipose tissue. The results showed 1,3-DCP dose dependently increased
      serum TG, TC and low-density lipoprotein cholesterol (LDL-C), decreased serum
      high-density lipoprotein cholesterol (HDL-C), increased relative liver weight,
      liver TG and TC, relative adipose tissue weight and enlarged the size of adipose
      cells. Because AMPK signal pathway is important in the process of lipid
      metabolism, we further investigated the effects of 1,3-DCP on AMPK signaling
      pathway in murine models. The results showed that 1,3-DCP (0.1-1 mg/kg/day)
      decreased p-AMPK/tAMPK ratio, p-ACC/tACC ratio, PPARalpha expression, but
      increased FAT, SREBP1, HMGCR and FAS expression. These observations indicated
      that 1,3-DCP induced hyperlipidemia in C57BL/6J mice at least partially through
      regulating AMPK signaling pathway.

PMID- 24333399
TI  - Deep brain stimulation as a treatment for neuropathic pain: a longitudinal study
      addressing neuropsychological outcomes.
AB  - Deep brain stimulation (DBS) of the periventricular/periaqueductal gray area and
      sensory thalamus can reduce pain intensity in patients with neuropathic pain.
      However, little is known about its impact on quality of life, emotional well
      being, and cognition. This study followed up 18 patients who had received DBS for
      neuropathic pain. Each participant had previously undergone psychometric
      evaluation of each of the above areas as part of a routine presurgical
      neuropsychological assessment. Commensurate measures were employed at a follow-up
      assessment at least 6 months postsurgery. DBS significantly improved mood,
      anxiety, and aspects of quality of life. Improvements correlated with reduced
      pain severity. However, the sample continued to show impairments in most areas
      when compared against normative data published on nonclinical samples. There was
      little change in general cognitive functioning, aside from deterioration in
      spatial working memory. However, improvements in pain severity were associated
      with less improvement (and even deterioration) on measures of executive cognitive
      functioning. Improvements in emotional well-being also were correlated with
      changes in cognition. These results suggest that DBS of the
      periventricular/periaqueductal gray and/or sensory thalamus improves quality of
      life and emotional well-being in sufferers, although there is some indication of
      executive dysfunction, particularly among those reporting greatest pain
      alleviation. PERSPECTIVE: This article examines the neuropsychological outcomes
      of DBS surgery as a treatment for neuropathic pain. This intervention was found
      to improve pain severity, emotional well-being, and quality of life, although
      such benefits may be accompanied by reduced ability on tasks measuring executive
      functioning.

PMID- 24333400
TI  - RGD decoration of PEGylated polyester nanocapsules of perfluorooctyl bromide for
      tumor imaging: influence of pre or post-functionalization on capsule morphology.
AB  - PEGylated polyester nanocapsules of perfluorooctyl bromide (PFOB) were surface
      decorated with a RGD (arginine-glycine-aspartic acid) peptide by either pre
      functionalization or post-functionalization strategies using carbodiimide
      assisted chemistry. Both strategies allowed successful linkage of RGD at the
      surface of nanocapsules with up to 600-950 peptide units per nanocapsule without
      modifying the encapsulation efficacy of PFOB used as the (19)F MRI imaging
      moiety. Cryo-Transmission Electron Microscopy images evidence that slight changes
      of the polymer used to form the capsule shell strongly influence nanocapsule
      morphology. While, the use of copolymer blends induces the formation of acorn
      morphologies, PLA-b-PEG-COOH leads to elongated and "tears of wine"-like
      nanoconstructs. In vivo evaluation in mice bearing CT26 tumors by (19)F MRI
      reveals no significant difference of accumulation between PEGylated and RGD
      decorated nanocapsules obtained by the post-functionalization approach (highest
      RGD density/capsule). 

PMID- 24333402
TI  - Nitric oxide-matrix metaloproteinase-9 interactions: biological and
      pharmacological significance--NO and MMP-9 interactions.
AB  - Nitric oxide (NO) and matrix metalloproteinase 9 (MMP-9) levels are found to
      increase in inflammation states and in cancer, and their levels may be
      reciprocally modulated. Understanding interactions between NO and MMP-9 is of
      biological and pharmacological relevance and may prove crucial in designing new
      therapeutics. The reciprocal interaction between NO and MMP-9 have been studied
      for nearly twenty years but to our knowledge, are yet to be the subject of a
      review. This review provides a summary of published data regarding the complex
      and sometimes contradictory effects of NO on MMP-9. We also analyse molecular
      mechanisms modulating and mediating NO-MMP-9 interactions. Finally, a potential
      therapeutic relevance of these interactions is presented.

PMID- 24333401
TI  - Passive and active strategies for transdermal delivery using co-encapsulating
      nanostructured lipid carriers: in vitro vs. in vivo studies.
AB  - This work aimed at designing a formulation based on nanostructured lipid carriers
      (NLC) for transdermal co-administration of olanzapine and simvastatin, using
      passive and active strategies in a combined in vitro/in vivo development
      approach. NLC were prepared by two distinct methods, namely solvent
      emulsification-evaporation (SE/E) and high pressure homogenization (HPH). HPH was
      selected on the basis of a better performance in terms of drug loading and in
      vitro permeation rate. Several mathematical models were used to elucidate the
      release mechanisms from lipid nanoparticles. In vitro release kinetics was shown
      to be driven by diffusion, but other mechanisms were also present, and supported
      the feasibility of using NLC for sustained drug delivery. The in vitro skin
      studies showed that the chemical penetration enhancers, limonene and ethanol,
      added to the NLC formulations, promoted a synergistic permeation enhancement of
      both drugs, with olanzapine exhibiting a higher permeation than simvastatin.
      Transdermal administration to rats resulted in steady-state levels reached at
      around 10h and maintained for 48h, again with olanzapine exhibiting a better
      permeation rate. The pharmacokinetic parameters indicated that the NLC dispersion
      displayed a better in vivo performance than the gel, which was consistent with
      the in vitro results. These differences were, however, negligible in the flux
      values, supporting the use of gel as a final, more convenient, formulation. The
      in vivo experiments in rats correlated well with in vitro findings and revealed
      that the combined use of ethanol and limonene, incorporated in the NLC
      formulation, provided the main driving force for drug permeation. The
      Dermaroller(r) pretreatment did not significantly enhance drug permeation,
      supporting the use of passive methods as suitable for a transdermal delivery
      system. Furthermore, this work may provide a promising proof-of-concept for
      further clinical application in the treatment of schizophrenia and associated
      disorders, combined with dyslipidemia. 

PMID- 24333403
TI  - The effect of a middle meatal antrostomy on nitric oxide ventilation in the
      maxillary sinus.
AB  - The effects of middle meatal antrostomy (MMA) on air and nitric oxide exchange in
      the human maxillary sinus were quantified using the computational fluid dynamics
      technique. One full period of respiration was considered in the anatomically
      correct numerical domain. The simulation results showed that MMA did not cause
      any noticeable change in the velocity or pressure fields at a global level but
      induced local velocity as high as 0.21m/s inside the maxillary. Therefore,
      enlargement of the ostium area by MMA allows inspiratory and expiratory nasal
      airflow to induce significant convective flows in the sinus, which in turn
      enhances gas exchange dramatically. At the end of the inspiration phase, NO
      concentration in the maxillary sinus decreased to about 54% of the initial value.
      NO concentration decreased only by about 30% during the expiration phase. This
      difference in reduction rate is thought to result from the difference in airflow
      velocity in the extended ostium during inspiration vs. expiration. 

PMID- 24333404
TI  - Mechanisms and treatments for renal artery stenosis.
AB  - Atherosclerotic renal artery stenosis (ARAS) is a common and complicated disease,
      which can result in high blood pressure and loss of kidney function. Although
      progress has been made in the understanding and treatment of hypertension in
      relation to ARAS, much less progress has been made in the area of renal function.
      Here we discuss current treatment options in regard to medical therapy and
      revascularization. We also describe the proposed mechanisms leading to renal
      dysfunction, including the CD40 signaling cascade, which is a particularly
      attractive signaling mechanism that may provide a mechanistic rationale for the
      development of renal disease in ARAS. 

PMID- 24333397
TI  - Cell based therapies for ischemic stroke: from basic science to bedside.
AB  - Cell therapy is emerging as a viable therapy to restore neurological function
      after stroke. Many types of stem/progenitor cells from different sources have
      been explored for their feasibility and efficacy for the treatment of stroke.
      Transplanted cells not only have the potential to replace the lost circuitry, but
      also produce growth and trophic factors, or stimulate the release of such factors
      from host brain cells, thereby enhancing endogenous brain repair processes.
      Although stem/progenitor cells have shown a promising role in ischemic stroke in
      experimental studies as well as initial clinical pilot studies, cellular therapy
      is still at an early stage in humans. Many critical issues need to be addressed
      including the therapeutic time window, cell type selection, delivery route, and
      in vivo monitoring of their migration pattern. This review attempts to provide a
      comprehensive synopsis of preclinical evidence and clinical experience of various
      donor cell types, their restorative mechanisms, delivery routes, imaging
      strategies, future prospects and challenges for translating cell therapies as a
      neurorestorative regimen in clinical applications. 

PMID- 24333405
TI  - Combination of virotherapy and T-cell therapy: arming oncolytic virus with T-cell
      engagers.
AB  - While cure rates for several cancers have significantly improved, the outcome for
      patients with advanced solid tumors remains grimly unchanged over the last
      decades. Thus, there is a need for new therapies that could improve outcome for
      patients who fail current therapies. Oncolytic vaccinia virus (VV) would be an
      appealing addition to the current therapies of cancers because of its ability to
      infect, replicate in, and lyse tumor cells, and spread to other tumor cells in
      successive rounds of replication. While clinical studies have demonstrated their
      safety, the antitumor efficacy of oncolytic VVs has been suboptimal. Oncolytic
      VVs' major mode of action is the destruction of tumor cells, which can
      subsequently activate a component of the immune system called T cells that can
      travel to distant sites and target against any tumor they find. At present, virus
      spread through tumors, as well as the activation of tumor-specific T cells, is
      limited, explaining the observed suboptimal antitumor activity of current
      oncolytic VVs. Thus it would be desirable to make the oncolytic VVs more powerful
      stimulators of immunity through activating resident T cells within the tumors so
      that they will kill tumor cells and stop new tumors from growing. To activate T
      cells within tumors, a new molecule called a T-cell engager that couples the T
      cell and the tumor cell, which increases the effectiveness of the T cells and
      their activation, has been constructed. This review summarizes the progress of
      the emerging field of combinations of oncolytic virotherapy and T-cell based
      therapy. 

PMID- 24333406
TI  - Pharmacogenomics in childhood rheumatic disorders: a foundation for future
      individualized therapy.
AB  - Investigating the effect of genotype on drug response in children is an evolving
      field, with many challenges, but there is great potential to optimize safe and
      effective use of drugs in children. An exponential increase in available
      medications for use in children with rheumatic disease has opened seemingly
      endless genotype/phenotype relationships to explore, but challenges inherent in
      studying rare diseases and the often overlooked role of ontogeny contribute to
      limitations in pharmacogenomic studies in this population. With careful
      recognition of the importance of development, improved phenotyping with the
      incorporation of biomarkers, and expanding collaborative efforts on a national
      and even international scale, the field of pediatric rheumatology has the
      opportunity to strategically study the new therapeutic armamentarium available
      and provide individualized/personalized safe and effective therapies to our
      population of patients. 

PMID- 24333407
TI  - Antidiabetic drugs and their potential role in treating mild cognitive impairment
      and Alzheimer's disease.
AB  - The incidence of both diabetes mellitus (DM) and dementia increases with aging
      and the incidence of dementia are higher in people with diabetes. Epidemiological
      and pathological data suggest that DM contributes to mild cognitive impairment
      (MCI) and dementia. DM seems to be an independent risk factor for MCI and
      Alzheimer's disease (AD) and is associated with more rapid cognitive decline.
      Recent evidence points out that insulin affects central nervous system functions,
      and can modulate cognitive functions. Impaired insulin signaling and insulin
      resistance in brain have been found to play an important role in the pathogenesis
      of AD. Human studies have shown that some oral antidiabetic medications can
      improve cognition in patients with MCI and AD. Intranasal insulin has also been
      shown to improve memory and cognitive abilities in MCI and AD patients. While it
      remains unclear whether management of diabetes will reduce the incidence of MCI
      and AD, emerging evidence suggests that diabetes therapies may improve cognitive
      function. 

PMID- 24333409
TI  - Advances in chimeric antigen receptor immunotherapy for chronic lymphocytic
      leukemia.
AB  - Despite the recent advances with targeted therapies in chronic lymphocytic
      leukemia (CLL), allogeneic hematopoietic stem cell transplantation (HSCT) remains
      the only curative option. However, this procedure is associated with significant
      morbidity and mortality due to high rates of infection and the toxicity of graft
      versus host disease (GVHD). One of the principle aims of cellular immunotherapy
      is to target the malignant cells without damaging the other tissues of the body.
      T lymphocytes offer the opportunity to do this, due to the exquisite specificity
      that they exhibit as part of the adaptive immune response. Chimeric antigen
      receptor (CAR) T cells are lymphocytes that have been genetically modified to
      express the antigen binding component of an immunoglobulin molecule coupled to T
      cell signaling domains. The use of an immunoglobulin molecule eliminates MHC
      restriction, enabling the same CAR to be used for several different patients and
      increasing the feasibility of widespread clinical use. They can be constructed to
      target a huge range of antigens, allowing the targeting of cancer cells with
      unprecedented levels of specificity. The addition of co-stimulatory domains to
      the CAR construct has enhanced the efficacy and durability of these T cells,
      which are under investigation in several clinical trials. The early results from
      these trials have been very encouraging with dramatic responses being observed in
      heavily pre-treated patients with otherwise poor risk disease. 

PMID- 24333408
TI  - Advances in chimeric antigen receptor immunotherapy for neuroblastoma.
AB  - Neuroblastoma (NBL) is the most common extracranial pediatric solid tumor and has
      heterogeneous biology and behavior. Patients with high-risk disease have poor
      prognosis despite complex multimodal therapy; therefore, novel curative
      approaches are needed. Immunotherapy is a novel therapeutic approach that
      harnesses the inherent activity of the immune system to control and eliminate
      malignant cells. One form of immunotherapy uses chimeric antigen receptors (CAR)
      to target tumor-associated antigens. CARs are derived from the antigen-binding
      domain of a monoclonal antibody (MAb) coupled with the intracellular signaling
      portion of the T cell receptor. CARs can combine the specificity and
      effectiveness of MAbs with the active bio-distribution, direct cytotoxicity, and
      long-term persistence of T cells. NBL provides an attractive target for CAR
      immunotherapy as many of its tumor-associated antigens are not expressed at
      significant levels on normal tissues, thus decreasing potential treatment related
      toxicity. Two previous clinical trials utilizing L1-cell adhesion molecule (L1
      CAM) and disialoganglioside (GD2) specific CARs (GD2-CAR) have demonstrated
      safety and anti-tumor efficacy in heavily pretreated relapsed/refractory
      neuroblastoma patients. Based on these promising results and on improved
      techniques that can further potentiate CAR therapies, two clinical trials are
      currently investigating the use of GD2-CARs in children with NBL. Several
      approaches may further enhance anti-tumor activity and persistence of CAR
      modified cells, and if these can be safely translated into the clinic, CAR-based
      immunotherapy could become a viable adjunct or potential alternative to
      conventional treatment options for patients with NBL. 

PMID- 24333410
TI  - Assessment of yeast chromosome XII instability: single chromosome comet assay.
AB  - The tools and techniques used in single-cell analysis of DNA damage in yeast
      Saccharomyces cerevisiae are limited. In this study, we modified the single cell
      gel electrophoresis assay, namely, the single chromosome comet assay based on DNA
      break analysis, at the chromosomal level. We studied the largest yeast chromosome
      XII, which contains the rDNA locus, and we investigated its instability using
      cell cycle checkpoint-, DNA damage- and antioxidative defence-deficient, and
      lifespan-deregulated yeast mutant strains. Moreover, we compared chromosome XII
      instability with the variability of nucleolar rDNA fluorescence signals. Three
      single-gene-deletion strains, cells lacking single-stranded DNA endonuclease,
      Rad1p; NAD(+)-dependent histone deacetylase, Sir2p; and gamma glutamylcysteine
      synthetase, Gsh1p, were more prone to chromosome XII instability compared to
      corresponding wildtype strains, indicating that DNA damage repair machinery,
      chromatin silencing and redox homeostasis may contribute to genome stability.
      Elevation in the number of DNA breaks was correlated with a high variability in
      the levels of nucleolar rDNA in the Deltarad1 background, while unaffected
      chromosome XII and low variability in nucleolar rDNA fluorescence signals were
      observed in the Deltator1 longevity mutant. Taken together, the single chromosome
      comet assay may be successfully used to study DNA damage at the chromosomal
      level, which might be overlooked using whole population analysis on DNA breaks
      with PFGE separation. 

PMID- 24333411
TI  - Embryonic exposure to corticosterone modifies aggressive behavior through
      alterations of the hypothalamic pituitary adrenal axis and the serotonergic
      system in the chicken.
AB  - Exposure to excess glucocorticoids (GCs) during embryonic development influences
      offspring phenotypes and behaviors and induces epigenetic modifications of the
      genes in the hypothalamic-pituitary-adrenal (HPA) axis and in the serotonergic
      system in mammals. Whether prenatal corticosterone (CORT) exposure causes similar
      effects in avian species is less clear. In this study, we injected low (0.2MUg)
      and high (1MUg) doses of CORT into developing embryos on day 11 of incubation
      (E11) and tested the changes in aggressive behavior and hypothalamic gene
      expression on posthatch chickens of different ages. In ovo administration of high
      dose CORT significantly suppressed the growth rate from 3weeks of age and
      increased the frequency of aggressive behaviors, and the dosage was associated
      with elevated plasma CORT concentrations and significantly downregulated
      hypothalamic expression of arginine vasotocin (AVT) and corticotropin-releasing
      hormone (CRH). The hypothalamic content of glucocorticoid receptor (GR) protein
      was significantly decreased in the high dose group (p<0.05), whereas no changes
      were observed for GR mRNA. High dose CORT exposure significantly increased
      platelet serotonin (5-HT) uptake, decreased whole blood 5-HT concentration
      (p<0.05), downregulated hypothalamic tryptophan hydroxylase 1 (TPH1) mRNA and
      upregulated 5-HT receptor 1A (5-HTR1A) and monoamine oxidase A (MAO-A) mRNA, but
      not monoamine oxidase B (MAO-B). High dose CORT also significantly increased DNA
      methylation of the hypothalamic GR and CRH gene promoters (p<0.05). Our findings
      suggest that embryonic exposure to CORT programs aggressive behavior in the
      chicken through alterations of the HPA axis and the serotonergic system, which
      may involve modifications in DNA methylation. 

PMID- 24333412
TI  - Decreasing prolactin levels leads to a lower diving effort but does not affect
      breeding success in Adelie penguins.
AB  - Current research on seabirds suggests a key role of hormones in the trade-off
      between self-maintenance and parental investment through their influence on
      foraging decisions during the breeding period. Although prolactin is known to
      have major effects on parental care, its role in foraging behavior has rarely
      been investigated in seabirds to date. The aim of this study was to assess the
      influence of an experimental decrease in prolactin levels on foraging decisions
      and its consequences on breeding success in free-living seabirds. To achieve
      this, we implanted bromocriptine (an inhibitor of prolactin secretion) in male
      Adelie penguins (Pygoscelis adeliae), monitored their foraging behavior using
      time-depth recorders over several trips, and recorded their reproductive output.
      On average 8+/-0.5days after implantation, we showed that bromocriptine
      administration led to an efficient decrease in prolactin levels. However, no
      differences were seen in foraging trip durations between bromocriptine-implanted
      birds and controls. Moreover, the time spent diving and the number of dives
      performed per trip were similar in both groups. By contrast, all diving
      parameters (including diving efficiency) were negatively affected by the
      treatment during the first at-sea trip following the treatment. Finally, the
      treatment did not affect adult body condition or chick growth and survival. Our
      study highlights the short-term negative effect of low prolactin levels on diving
      effort, but indicates that a short-term and/or low-magnitude decrease in
      prolactin levels alone is not sufficient to modify consistently the body
      maintenance or the parental investment of Adelie penguins. 

PMID- 24333413
TI  - Kruppel-like transcription factor 11 (KLF11) overexpression inhibits cardiac
      hypertrophy and fibrosis in mice.
AB  - The Kruppel-like factors (KLFs) belong to a subclass of Cys2/His2 zinc-finger DNA
      binding proteins. The KLF family member KLF11 is originally identified as a
      transforming growth factor beta (TGF-beta)-inducible gene and is one of the most
      studied in this family. KLF11 is expressed ubiquitously and participates in
      diabetes and regulates hepatic lipid metabolism. However, the role of KLF11 in
      cardiovascular system is largely unknown. Here in this study, we reported that
      KLF11 expression is down-regulated in failing human hearts and hypertrophic
      murine hearts. To evaluate the roles of KLF11 in cardiac hypertrophy, we
      generated cardiac-specific KLF11 transgenic mice. KLF11 transgenic mice do not
      show any difference from their littermates at baseline. However, cardiac-specific
      KLF11 overexpression protects mice from TAC-induced cardiac hypertrophy, with
      reduced radios of heart weight (HW)/body weight (BW), lung weight/BW and HW/tibia
      length, decreased left ventricular wall thickness and increased fractional
      shortening. We also observe lower expression of hypertrophic fetal genes in TAC
      challenged KLF11 transgenic mice compared with WT mice. In addition, KLF11
      reduces cardiac fibrosis in mice underwent hypertrophy. The expression of
      fibrosis markers are also down-regulated when KLF11 is overexpressed in TAC
      challenged mice. Taken together, our findings identify a novel anti-hypertrophic
      and anti-fibrotic role of KLF11, and KLF11 activator may serve as candidate drug
      for heart failure patients. 

PMID- 24333414
TI  - The cytoprotective role of autophagy in puromycin aminonucleoside treated human
      podocytes.
AB  - Autophagy is a ubiquitous catabolic process involving degradation of damaged
      organelles and protein aggregates. It shows cytoprotective effects in many cell
      types and helps to maintain cell homeostasis. In many glomerular diseases,
      podocyte damage leads to the disruption of the renal filtration barrier and
      subsequent proteinuria. Puromycin aminonucleoside (PAN) which induces podocyte
      apoptosis in vitro and in vivo is widely used for studying the pathophysiology of
      glomerular diseases. It has been shown that PAN induces autophagy in podocytes.
      However, the relationship between autophagy and apoptosis in PAN treated human
      podocytes is not known and the role of PAN-induced autophagy in podocyte survival
      remains unclear. Here we demonstrate that PAN induced autophagy in human
      podocytes prior to apoptosis which was featured with the activation of mTOR
      complex 1 (mTORC1). When the PAN-induced autophagy was inhibited by 3
      methyladenine (3-MA) or chloroquine (CQ), podocyte apoptosis increased
      significantly along with the elevation of active caspase-3. Under such
      circumstance, the podocyte cytoskeleton was also disrupted. Collectively, our
      results suggested that the induced autophagy may be an early adaptive
      cytoprotective mechanism for podocyte survival after PAN treatment. 

PMID- 24333415
TI  - Clock upregulates intercellular adhesion molecule-1 expression and promotes
      mononuclear cells adhesion to endothelial cells.
AB  - Clock is a basic helix-loop-helix (bHLH) transcription factor that plays
      important role in circadian rhythms of various physiological functions. Previous
      study showed that the expression of intercellular adhesion molecule-1 (ICAM-1)
      was reduced in the liver tissues of Clock mutant mice. However, how Clock
      regulates ICAM-1 expression and whether Clock affects cell adhesion function
      remain unknown. In the present study, we found that exogenous expression of Clock
      upregulated the gene expressions of ICAM-1 and other adhesion-related genes
      including VCAM1 and CCL-2, and increased the transcriptional activity of ICAM-1
      in mouse brain microvascular endothelial cell lines. In contrast, loss of Clock
      decreased these gene expressions and ICAM-1 transcriptional activity. Chromatin
      immunoprecipitation (ChIP) assay revealed that Clock binds to the E-box-like
      enhancer of ICAM-1 gene. ICAM-1 gene showed rhythmic expression in endothelial
      cells after serum shock in vitro, suggesting ICAM-1 may be a Clock-controlled
      gene. Clock regulates the adhesion of mononuclear cells to endothelial cells via
      ICAM-1. Together, our findings show that Clock is a positive regulator of ICAM-1,
      and promotes the adhesion of mononuclear cells to endothelial cells. 

PMID- 24333416
TI  - Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via
      persistent DNA damage.
AB  - Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates
      various aspects of cancer progression, including migration, invasion and
      angiogenesis. However, the possible association of HAS2 with the response of
      cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we
      show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis
      in cancer cells. Upon exposure to radiation, all of the tested human cancer cell
      lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24h.
      Inhibition of HAS2 induction significantly reduced the survival of irradiated
      radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the
      cells to sustain irradiation-induced DNA damage, thereby leading to an increase
      of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer
      cells to radiation via persistent DNA damage, further suggesting that the
      irradiation-induced up-regulation of HAS2 contributes to the radioresistance of
      cancer cells. Thus, HAS2 could potentially be targeted for therapeutic
      interventions aimed at radiosensitizing cancer cells. 

PMID- 24333417
TI  - IRS1Ser307 phosphorylation does not mediate mTORC1-induced insulin resistance.
AB  - Increased mammalian target of rapamycin complex 1 (mTORC1) activity has been
      suggested to play important roles in development of insulin resistance in
      obesity. mTORC1 hyperactivity also increases endoplasmic reticulum (ER) stress,
      which in turn contributes to development of insulin resistance and glucose
      intolerance. Increased IRS1 phosphorylation at Ser307 in vitro is correlated with
      mTORC1- and ER stress-induced insulin resistance. This phosphorylation site
      correlates strongly with impaired insulin receptor signaling in diabetic mice and
      humans. In contrast, evidence from knock-in mice suggests that phosphorylation of
      IRS1 at Ser307 is actually required to maintain insulin sensitivity. To study the
      involvement of IRS1(Ser307) phosphorylation in mTORC1-mediated glucose
      intolerance and insulin sensitivity in vivo, we investigated the effects of liver
      specific TSC1 depletion in IRS1(Ser307Ala) mice and controls. Our results
      demonstrate that blockade of IRS1(Ser307) phosphorylation in vivo does not
      prevent mTORC1-mediated glucose intolerance and insulin resistance. 

PMID- 24333418
TI  - Imaging Axl expression in pancreatic and prostate cancer xenografts.
AB  - The receptor tyrosine kinase Axl is overexpressed in and leads to patient
      morbidity and mortality in a variety of cancers. Axl-Gas6 interactions are
      critical for tumor growth, angiogenesis and metastasis. The goal of this study
      was to investigate the feasibility of imaging graded levels of Axl expression in
      tumors using a radiolabeled antibody. We radiolabeled anti-human Axl (Axl mAb)
      and control IgG1 antibodies with (125)I with high specific radioactivity and
      radiochemical purity, resulting in an immunoreactive fraction suitable for in
      vivo studies. Radiolabeled antibodies were investigated in severe combined
      immunodeficient mice harboring subcutaneous CFPAC (Axl(high)) and Panc1
      (Axl(low)) pancreatic cancer xenografts by ex vivo biodistribution and imaging.
      Based on these results, the specificity of [(125)I]Axl mAb was also validated in
      mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring
      subcutaneous 22Rv1 (Axl(low)) or DU145 (Axl(high)) prostate tumors by ex vivo
      biodistribution and imaging studies at 72h post-injection of the antibody. Both
      imaging and biodistribution studies demonstrated specific and persistent
      accumulation of [(125)I]Axl mAb in Axl(high) (CFPAC and DU145) expression tumors
      compared to the Axl(low) (Panc1 and 22Rv1) expression tumors. Axl expression in
      these tumors was further confirmed by immunohistochemical studies. No difference
      in the uptake of radioactivity was observed between the control [(125)I]IgG1
      antibody in the Axl(high) and Axl(low) expression tumors. These data demonstrate
      the feasibility of imaging Axl expression in pancreatic and prostate tumor
      xenografts. 

PMID- 24333419
TI  - The control of lipid metabolism by mRNA splicing in Drosophila.
AB  - The storage of lipids is an evolutionarily conserved process that is important
      for the survival of organisms during shifts in nutrient availability.
      Triglycerides are stored in lipid droplets, but the mechanisms of how lipids are
      stored in these structures are poorly understood. Previous in vitro RNAi screens
      have implicated several components of the spliceosome in controlling lipid
      droplet formation and storage, but the in vivo relevance of these phenotypes is
      unclear. In this study, we identify specific members of the splicing machinery
      that are necessary for normal triglyceride storage in the Drosophila fat body.
      Decreasing the expression of the splicing factors U1-70K, U2AF38, U2AF50 in the
      fat body resulted in decreased triglyceride levels. Interestingly, while
      decreasing the SR protein 9G8 in the larval fat body yielded a similar
      triglyceride phenotype, its knockdown in the adult fat body resulted in a
      substantial increase in lipid stores. This increase in fat storage is due in part
      to altered splicing of the gene for the beta-oxidation enzyme CPT1, producing an
      isoform with less enzymatic activity. Together, these data indicate a role for
      mRNA splicing in regulating lipid storage in Drosophila and provide a link
      between the regulation of gene expression and lipid homeostasis. 

PMID- 24333420
TI  - 8-Oxo-2'-deoxyguanosine ameliorates features of metabolic syndrome in obese mice.
AB  - Metabolic syndrome describes a group of clinical features that together increase
      the incidence of coronary artery disease, stroke and type 2 diabetes. Insulin
      resistance is a major risk factor for developing metabolic syndrome. A chronic
      state of inflammation accompanies the accumulation of surplus lipids in adipose
      and liver tissue, frequently involved in insulin resistance. 8-Oxo-2'
      deoxyguanosine (8-Oxo-dG) is a potent anti-inflammatory agent that inactivates
      both Rac1 and Rac2 which are critical to initiating the inflammatory responses in
      various cell types, including macrophages. In this study, we explored whether 8
      Oxo-dG suppressed a series of systemic inflammatory cascades, resulting in the
      amelioration of typical features of metabolic syndrome in obese mice. The results
      demonstrate that 8-Oxo-dG effectively improved hyperglycemia, dyslipidemia and
      fatty liver changes in obese mice. The level of biochemical markers indicative of
      systemic inflammation were reduced in 8-Oxo-dG treated mice, whereas serum levels
      of adiponectin, a crucial factor associated with improved metabolic syndrome,
      were enhanced. Our results demonstrate that 8-Oxo-dG effectively disrupts the
      pathogenesis of insulin resistance and obesity-associated metabolic syndrome. 

PMID- 24333422
TI  - Inversed relationship between CD44 variant and c-Myc due to oxidative stress
      induced canonical Wnt activation.
AB  - Cancer stem-like cells express high amount of CD44 variant8-10 which protects
      cancer cells from redox stress. We have demonstrated by immunohistochemical
      analysis and Western blotting, and reverse-transcription polymerase chain
      reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression
      manner in gastric cancer cells. That is attributable to the oxidative stress
      induced canonical Wnt activation, and furthermore, the up-regulation of the
      downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in
      CD44 variant-positive cancer cells. We have also found out that CD44v8-10
      expression is associated with the turn-over of the c-Myc with the experiments
      using gastric cancer cell lines. This cannot be simply explained by the model of
      oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are
      enriched at the invasive front. Tumor tissue at the invasive area is considered
      to be composed of heterogeneous cellular population; dormant cancer stem-like
      cells with CD44v8-10 (high)/ Fbw7 (high)/ c-Myc (low) and proliferative cancer
      stem-like cells with CD44v8-10 (high)/ Fbw7 (low)/ c-Myc (high). 

PMID- 24333421
TI  - Altered expression of calcineurin, calpain, calpastatin and HMWCaMBP in cardiac
      cells following ischemia and reperfusion.
AB  - A rise in intracellular myocardial Ca(2+) during cardiac ischemia activates
      calpain (Calpn) thereby causing damage to myocardial proteins, which leads to
      myocyte death and consequently to loss of myocardial structure and function.
      Calcineurin (CaN) interacts with Calpn and causes cellular damage eventually
      leading to cell death. Calpastatin (Calp) and high molecular weight calmodulin
      binding protein (HMWCaMBP) (homolog of Calp), inhibit Calpn activity and thus
      prevent cell death. CaN stimulation can also result in self-repair of damaged
      cardiomyocytes. The present study attempts to elucidate the expression of these
      proteins in cells under pre-ischemic condition (control), following ischemia
      induction and also reperfusion subsequent to ischemia. For the first time, flow
      cytometric analysis (FACS) has been used for analyzing protein expression
      concurrently with viability. We induced ischemia and subsequently reperfusion in
      80% confluent cultures of neonatal murine cardiomyocytes (NMCC). Viability
      following induction was assessed with 7-AAD staining and the cells were
      simultaneously checked for protein expression by FACS. We observed that ischemia
      induction results in increased expression of CaN, Calp and Calpn. HMWCaMBP
      expression was reduced in live cells following ischemia which suggests that there
      is a poor survival outcome of cells expressing HMWCaMBP thereby making it a
      potential biomarker for such cells. Most live cells following ischemia expressed
      CaN pointing towards self-repair and favorable survival outcomes. 

PMID- 24333423
TI  - Effect of a cholesterol-rich lipid environment on the enzymatic activity of
      reconstituted hyaluronan synthase.
AB  - Hyaluronan synthase (HAS) is a unique membrane-associated glycosyltransferase and
      its activity is lipid dependent. The dependence however is not well understood,
      especially in vertebrate systems. Here we investigated the functional association
      of hyaluronan synthesis in a cholesterol-rich membrane-environment. The culture
      of human dermal fibroblasts in lipoprotein-depleted medium attenuated the
      synthesis of hyaluronan. The sequestration of cellular cholesterol by methyl-beta
      cyclodextrin also decreased the hyaluronan production of fibroblasts, as well as
      the HAS activity. To directly evaluate the effects of cholesterol on HAS
      activity, a recombinant human HAS2 protein with a histidine-tag was expressed as
      a membrane protein by using a baculovirus system, then successfully solubilized,
      and isolated by affinity chromatography. When the recombinant HAS2 proteins were
      reconstituted into liposomes composed of both saturated phosphatidylcholine and
      cholesterol, this provided a higher enzyme activity as compared with the
      liposomes formed by phosphatidylcholine alone. Cholesterol regulates HAS2
      activity in a biphasic manner, depending on the molar ratio of
      phosphatidylcholine to cholesterol. Furthermore, the activation profiles of
      different lipid compositions were determined in the presence or absence of
      cholesterol. Cholesterol had the opposite effect on the HAS2 activity in
      liposomes composed of phosphatidylethanolamine or phosphatidylserine. Taken
      together, the present data suggests a clear functional association between HAS
      activity and cholesterol-dependent alterations in the physical and chemical
      properties of cell membranes. 

PMID- 24333425
TI  - Knockdown of p53 suppresses Nanog expression in embryonic stem cells.
AB  - Mouse embryonic stem cells (ESCs) express high levels of cytoplasmic p53.
      Exposure of mouse ESCs to DNA damage leads to activation of p53, inducing Nanog
      suppression. In contrast to earlier studies, we recently reported that chemical
      inhibition of p53 suppresses ESC proliferation. Here, we confirm that p53
      signaling is involved in the maintenance of mouse ESC self-renewal. RNA
      interference-mediated knockdown of p53 induced downregulation of p21 and defects
      in ESC proliferation. Furthermore, p53 knockdown resulted in a significant
      downregulation in Nanog expression at 24 and 48 h post-transfection. p53
      knockdown also caused a reduction in Oct4 expression at 48 h post-transfection.
      Conversely, exposure of ESCs to DNA damage caused a higher reduction of Nanog
      expression in control siRNA-treated cells than in p53 siRNA-treated cells. These
      data show that in the absence of DNA damage, p53 is required for the maintenance
      of mouse ESC self-renewal by regulating Nanog expression.

PMID- 24333424
TI  - A unique F-type H+-ATPase from Streptococcus mutans: an active H+ pump at acidic
      pH.
AB  - We have shown previously that the Streptococcus mutans F-type H(+)-ATPase
      (F(O)F(1)) c subunit gene could complement Escherichia coli defective in the
      corresponding gene, particularly at acidic pH (Araki et al., (2013) [14]). In
      this study, the entire S. mutans F(O)F(1) was functionally assembled in the E.
      coli plasma membrane (SF(O)F(1)). Membrane SF(O)F(1) ATPase showed optimum
      activity at pH 7, essentially the same as that of the S. mutans, although the
      activity of E. coli F(O)F(1) (EF(O)F(1)) was optimum at pH>=9. The membranes
      showed detectable ATP-dependent H(+)-translocation at pH 5.5-6.5, but not at
      neutral conditions (pH>=7), consistent with the role of S. mutans F(O)F(1) to
      pump H(+) out of the acidic cytoplasm. A hybrid F(O)F(1), consisting of membrane
      integrated F(O) and -peripheral F(1) sectors from S. mutans and E. coli
      (SF(O)EF(1)), respectively, essentially showed the same pH profile as that of
      EF(O)F(1) ATPase. However, ATP-driven H(+)-transport was similar to that by
      SF(O)F(1), with activity at acidic pH. Replacement of the conserved c subunit
      Glu53 in SF(O)F(1) abolished H(+)-transport at pH 6 or 7, suggesting its role in
      H(+) transport. Mutations in the SF(O)F(1) c subunit, Ser17Ala or Glu20Ile,
      changed the pH dependency of H(+)-transport, and the F(O) could transport H(+) at
      pH 7, as the membranes with EF(O)F(1). Ser17, Glu20, and their vicinity were
      suggested to be involved in H(+)-transport in S. mutans at acidic pH.

PMID- 24333426
TI  - HER4 selectively coregulates estrogen stimulated genes associated with breast
      tumor cell proliferation.
AB  - The EGFR-family member HER4 undergoes regulated intramembrane proteolysis (RIP)
      to generate an intracellular domain (4ICD) that functions as a transcriptional
      coactivator. Accordingly, 4ICD coactivates the estrogen receptor (ER) and
      associates with ER at target gene promoters in breast tumor cells. However, the
      extent of 4ICD coactivation of ER and the functional significance of the 4ICD/ER
      transcriptional complex is unclear. To identify 4ICD coactivated genes we
      performed a microarray gene expression analysis of beta-estradiol treated cells
      comparing control MCF-7 breast cancer cells to MCF-7 cells where HER4 expression
      was stably suppressed using a shRNA. In the MCF-7 cell line, beta-estradiol
      significantly stimulated or repressed by 2-fold or more 726 or 53 genes,
      respectively. Significantly, HER4/4ICD was an obligate coactivator for 277 or 38%
      of the beta-estradiol stimulated genes. Ingenuity Pathway Analysis of beta
      estradiol regulated genes identified significant associations with multiple
      cellular functions regulating cellular growth and proliferation, cell cycle
      progression, cancer metastasis, decreased hypoplasia, tumor cell migration,
      apoptotic resistance of tumor cells, and increased transcription. Genes
      coactivated by 4ICD displayed functional specificity by only significantly
      contributing to cellular growth and proliferation, cell cycle progression, and
      decreased hypoplasia. In direct concordance with these in situ results we show
      that HER4 knockdown in MCF-7 cells results in a loss of estrogen stimulated tumor
      cell proliferation and cell cycle progression, whereas, estrogen stimulated tumor
      cell migration was unaffected by loss of HER4 expression. In summary, we
      demonstrate for the first time that a cell surface receptor functions as an
      obligate ER coactivator with functional specificity associated with breast tumor
      cell proliferation and cell cycle progression. Nearly 90% of ER positive tumors
      coexpress HER4, therefore we predict that the majority of breast cancer patients
      would benefit from a strategy to therapeutic disengage ER/4ICD coregulated tumor
      cell proliferation. 

PMID- 24333427
TI  - Measurement of HMG CoA reductase activity in different human cell lines by ultra
      performance liquid chromatography tandem mass spectrometry.
AB  - Hydroxymethylglutaryl coenzyme A reductase (HMGCR) catalyzes the rate limiting
      step in cholesterol biosynthesis converting HMG-CoA into mevalonic acid (MVA),
      which equilibrates with mevalonic acid lactone (MVL) under neutral pH conditions.
      We developed a fast, sensitive, and efficient method to determine HMGCR activity
      in human cell lines measuring MVL levels by ultra-performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS). Convenient prepared samples
      containing MVL-D7 as an internal standard were injected, separated, and eluted
      from an ACQUITY HSS PFP column. Measurement of MVL was performed by electrospray
      ionization mass spectrometry with multiple reaction monitoring. Calibration
      curves were linear and reproducible in the range of 0.15-165 MUg/l (r>0.99).
      Lower limit of quantification was 0.12 MUg/l. Intra- and interassay imprecision
      were <1.3% and <2.9%, respectively. HMGCR enzymatic activity measurements of
      cells cultivated under different cell culture conditions (with 10% FCS, with 10%
      lipoprotein-deficient serum and under serum starvation) revealed the
      applicability of this test system for various experimental settings. This
      efficient UPLC-MS/MS assay permits rapid and high sensitive determination of
      HMGCR enzyme activity, tracing potential alterations in cholesterol biosynthesis.

PMID- 24333428
TI  - Evolutionarily conserved IMPACT impairs various stress responses that require
      GCN1 for activating the eIF2 kinase GCN2.
AB  - In response to a range of environmental stresses, phosphorylation of the alpha
      subunit of the translation initiation factor 2 (eIF2alpha) represses general
      protein synthesis coincident with increased translation of specific mRNAs, such
      as those encoding the transcription activators GCN4 and ATF4. The eIF2alpha
      kinase GCN2 is activated by amino acid starvation by a mechanism involving GCN2
      binding to an activator protein GCN1, along with association with uncharged tRNA
      that accumulates during nutrient deprivation. We previously showed that mammalian
      IMPACT and its yeast ortholog YIH1 bind to GCN1, thereby preventing GCN1
      association with GCN2 and stimulation of this eIF2alpha kinase during amino acid
      depletion. GCN2 activity is also enhanced by other stresses, including proteasome
      inhibition, UV irradiation and lack of glucose. Here, we provide evidence that
      IMPACT affects directly and specifically the activation of GCN2 under these
      stress conditions in mammalian cells. We show that activation of mammalian GCN2
      requires its interaction with GCN1 and that IMPACT promotes the dissolution of
      the GCN2-GCN1 complex. To a similar extent as the overexpression of YIH1,
      overexpression of IMPACT in yeast cells inhibited growth under all stress
      conditions that require GCN2 and GCN1 for cell survival, including exposure to
      acetic acid, high levels of NaCl, H2O2 or benomyl. This study extends our
      understanding of the roles played by GCN1 in GCN2 activation induced by a variety
      of stress arrangements and suggests that IMPACT and YIH1 use similar mechanisms
      for regulating this eIF2alpha kinase.

PMID- 24333429
TI  - Dioscin inhibits osteoclast differentiation and bone resorption though down
      regulating the Akt signaling cascades.
AB  - Bone resorption is the unique function of osteoclasts (OCs) and is critical for
      both bone homeostasis and pathologic bone diseases including osteoporosis,
      rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural
      compounds that may suppress osteoclast formation and/or function is promising for
      the treatment of osteoclast-related diseases. In this study, we for the first
      time demonstrated that dioscin suppressed RANKL-mediated osteoclast
      differentiation and bone resorption in vitro in a dose-dependent manner. The
      suppressive effect of dioscin is supported by the reduced expression of
      osteoclast-specific markers. Further molecular analysis revealed that dioscin
      abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear
      factor-kappaB (NF-kappaB) signaling pathway and inhibited NFATc1 transcriptional
      activity. Moreover, in vivo studies further verified the bone protection activity
      of dioscin in osteolytic animal model. Together our data demonstrate that dioscin
      suppressed RANKL-induced osteoclast formation and function through Akt signaling
      cascades. Therefore, dioscin is a potential natural agent for the treatment of
      osteoclast-related diseases. 

PMID- 24333430
TI  - Liver X receptors interfere with the deleterious effect of diethylstilbestrol on
      testicular physiology.
AB  - Liver X receptors LXRalpha (NR1H3) and LXRbeta (NR1H2) are transcription factors
      belonging to the nuclear receptor superfamily, activated by specific oxysterols,
      oxidized derivatives of cholesterol. These receptors are involved in the
      regulation of testis physiology. Lxr-deficient mice pointed to the physiological
      roles of these nuclear receptors in steroid synthesis, lipid homeostasis and germ
      cell apoptosis and proliferation. Diethylstilbestrol (DES) is a synthetic
      estrogen considered as an endocrine disruptor that affects the functions of the
      testis. Various lines of evidences have made a clear link between estrogens,
      their nuclear receptors ERalpha (NR3A1) and ERbeta (NR3A2), and Lxralpha/beta. As
      LXR activity could also be regulated by the nuclear receptor small heterodimer
      partner (SHP, NR0A2) and DES could act through SHP, we wondered whether LXR could
      be targeted by estrogen-like endocrine disruptors such as DES. For that purpose,
      wild-type and Lxr-deficient mice were daily treated with 0.75 MUg DES from days 1
      to 5 after birth. The effects of DES were investigated at 10 or 45 days of age.
      We demonstrated that DES induced a decrease of the body mass at 10 days only in
      the Lxr-deficient mice suggesting a protective effect of Lxr. We defined three
      categories of DES-target genes in testis: those whose accumulation is independent
      of Lxr; those whose accumulation is enhanced by the lack of both Lxralpha/beta;
      those whose accumulation is repressed by the absence of Lxralpha/beta. Lipid
      accumulation is also modified by neonatal DES injection. Lxr-deficient mice
      present different lipid profiles, demonstrating that DES could have its effects
      in part due to Lxralpha/beta. Altogether, our study shows that both nuclear
      receptors Lxralpha and Lxrbeta are not only basally important for testicular
      physiology but could also have a preventive effect against estrogen-like
      endocrine disruptors.

PMID- 24333431
TI  - The SufBCD protein complex is the scaffold for iron-sulfur cluster assembly in
      Thermus thermophiles HB8.
AB  - Iron-sulfur (Fe-S) clusters are the oldest and most versatile inorganic cofactors
      that are required to sustain fundamental life processes. Bacteria have three
      systems of [Fe-S] cluster biogenesis, designated ISC, NIF, and SUF. In contrast,
      the Thermus thermophiles HB8 has only one system, formed mostly by SUF homologs
      that contain six proteins: SufA, SufB, SufC, SufD, SufS and SufE. The kinetics of
      SufC ATPase was studied using a linked enzyme assay method. In the presence of
      SufB, SufD or SufBD complexes, the activity of SufC was enhanced. The cysteine
      desulfurase activity of SufS was also stimulated by the presence of the SufBCD
      complex. The results obtained through enzymology revealed that aconitase activity
      was activated by [Fe-S] clusters reconstituted on the SufBCD complex.
      Consolidated results from spectral and enzymatic analysis suggest that the SufBCD
      complex is a novel type of Fe-S scaffold system that can assemble Fe/S clusters
      de novo. 

PMID- 24333432
TI  - GSK3beta negatively regulates HIF1alpha mRNA stability via nucleolin in the MG63
      osteosarcoma cell line.
AB  - Hypoxia-inducible factor 1alpha (HIF1alpha) is a transcription factor involved in
      the growth, invasion and metastasis of malignant tumors. Glycogen synthase kinase
      3 beta (GSK3beta) is a protein kinase involved in a variety of signaling
      pathways, such as the Wnt and NF-kappaB pathways; this kinase can affect tumor
      progress through the regulation of transcription factor expression and apoptosis.
      Recent studies showed that GSK3beta was involved in the expression of HIF1alpha.
      However, the effect of GSK3beta on HIF1alpha expression in osteosarcoma cells
      remains unknown. To understand the relationship between GSK3beta and HIF1alpha
      comprehensively, small RNA interference techniques, Western blot analyses,
      quantitative real-time PCR analyses and luciferase assays were used in our study.
      Experimental data revealed that inhibition of GSK3beta could increase HIF1alpha
      protein levels and expression of its target genes by increasing the stability of
      the HIF1alpha mRNA, not by affecting the HIF1alpha protein stability, and that
      this process could be mediated by nucleolin. 

PMID- 24333434
TI  - Extreme rapid warming yields high functional survivals of vitrified 8-cell mouse
      embryos even when suspended in a half-strength vitrification solution and cooled
      at moderate rates to -196 degrees C.
AB  - To cryopreserve cells, it is essential to avoid intracellular ice formation
      during cooling and warming. One way to do so is to subject them to procedures
      that convert cell water into a non-crystalline glass. Current belief is that to
      achieve this vitrification, cells must be suspended in very high concentrations
      of glass-inducing solutes (i.e., >=6 molal) and cooled at very high rates (i.e.,
      ?1000 degrees C/min). We report here that both these beliefs are incorrect with
      respect to the vitrification of 8-cell mouse embryos. In this study,
      precompaction 8-cell embryos were vitrified in several dilutions of EAFS10/10
      using various cooling rates and warming rates. Survival was based on morphology,
      osmotic functionality, and on the ability to develop to expanded blastocysts.
      With a warming rate of 117,500 degrees C/min, the percentages of embryos
      vitrified in 1*, 0.75*, and 0.5* EAFS that developed to blastocysts were 93%,
      92%, and 83%, respectively. And the percentages of morphological survivors that
      developed to expanded blastocysts were 100%, 92%, and 97%, respectively. Even
      when the solute concentration of the EAFS was reduced to 33% of normal, we
      obtained 40% functional survival of these 8-cell embryos.

PMID- 24333433
TI  - Forced running exercise attenuates hippocampal neurogenesis impairment and the
      neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated
      pathway.
AB  - Cranial radiotherapy induces progressive and debilitating cognitive deficits,
      particularly in long-term cancer survivors, which may in part be caused by the
      reduction of hippocampal neurogenesis. Previous studies suggested that voluntary
      exercise can reduce the cognitive impairment caused by radiation therapy.
      However, there is no study on the effect of forced wheel exercise and little is
      known about the molecular mechanisms mediating the effect of exercise. In the
      present study, we investigated whether the forced running exercise after
      irradiation had the protective effects of the radiation-induced cognitive
      impairment. Sixty-four Male Sprague-Dawley rats received a single dose of 20Gy or
      sham whole-brain irradiation (WBI), behavioral test was evaluated using open
      field test and Morris water maze at 2months after irradiation. Half of the rats
      accepted a 3-week forced running exercise before the behavior detection.
      Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis
      and Western blotting was used to assess changes in the levels of mature brain
      derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B
      (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase
      (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response
      element binding protein (CREB) in the BDNF-pCREB signaling. We found forced
      running exercise significantly prevented radiation-induced cognitive deficits,
      ameliorated the impairment of hippocampal neurogenesis and attenuated the down
      regulation of these proteins. Moreover, exercise also increased behavioral
      performance, hippocampal neurogenesis and elevated BDNF-pCREB signaling in non
      irradiation group. These results suggest that forced running exercise offers a
      potentially effective treatment for radiation-induced cognitive deficits. 

PMID- 24333435
TI  - Toll-like receptor 22 of gilthead seabream, Sparus aurata: molecular cloning,
      expression profiles and post-transcriptional regulation.
AB  - TLR22 is a fish-specific TLR that recognizes dsRNAs. In the present study, a
      TLR22 homologue gene from gilthead seabream (sbTLR22) was identified and
      characterized. The full coding sequence contained a single open-reading frame of
      2895 nucleotides encoding a predicted protein of 964 amino acids in length. Its
      3'-UTR was relatively long, 1380 nucleotides, and contained three AU-rich
      sequences frequently associated with mRNA instability. Functional studies showed
      that the sbTLR22 transcript had a short half-life, although the three AU-rich
      sequences in its 3'-UTR did not seem to be related with this fact. The sbTLR22
      was highly expressed in the spleen, thymus and gills of healthy fish. After
      Vibrio anguillarum infection, the mRNA levels of sbTLR22 increased greatly in
      head kidney, blood and peritoneal exudate, but were only moderately induced in
      spleen and liver, suggesting the involvement of sbTLR22 in the immune response
      against bacterial infections. In addition, acidophilic granulocytes and
      macrophages, both considered professional phagocytes in seabream, displayed cell
      type-specific sbTLR22 expression profiles when stimulated with different pathogen
      associated molecular patterns (PAMPs). Although acidophilic granulocytes
      expressed sbTLR22, polyinosinic:polycytidylic acid (poly I:C) was unable to up
      regulate the expression of this receptor. In contrast, poly I:C induced the
      expression of sbTLR22 in macrophages, in a process that was partially endosome
      dependent. Taken together, our results suggest that sbTLR22 is involved in
      bacterial infection and might sense bacterial PAMPs. 

PMID- 24333436
TI  - Characterization and expression of the CXCR1 and CXCR4 in miiuy croaker and
      evolutionary analysis shows the strong positive selection pressures imposed in
      mammal CXCR1.
AB  - The innate immune system can recognize non-self, danger signals, and pathogen
      associated molecular patterns and provides a first line of antimicrobial host
      defense. Therefore, it plays an instructive role and is pretty important in
      vertebrates. In innate immune responses, CXCRs act as the main receptors of CXC
      chemokines and play a vital role in host defense and inflammation. In present
      study, we cloned two cDNA molecules of CXCR1 and CXCR4 in Miichthys miiuy (miiuy
      croaker). In these two genes, we found the most highly conserved DRY motif in the
      second intracellular loop adjacent to the third transmembrane domain. The
      expressions of CXCR1 and CXCR4 showed that they were ubiquitously expressed in
      ten normal tissues. After infection with Vibrio anguillarum and Vibrio harveyi,
      the expressions of CXCRs in the immune tissues were significantly regulated in
      most of tissues except that of CXCR1 in the kidney after V. harveyi injection.
      Evolutionary analysis showed that only the ancestral lineages of CXCR4 in
      amphibians underwent positive selection, indicating that the ancestors of
      amphibians boarded the land and had to further evolve to adapt to terrestrial
      environments. Multiple ML methods were implemented to detect the robust
      positively selected candidates for sites. In total, we detected 12 and 3
      positively selected sites in the subsets of current mammal and fish CXCR1 genes,
      and only one site under positive selection was found in mammalian CXCR4 subsets.
      These positively selected sites were mainly located in the extracellular domains
      of CXCRs. The sliding window analysis and evolution test tended to favor positive
      selection acting on the N-terminal domain of CXCR1, which was the critical region
      for ligand/receptor signaling for neutrophils and receptor-ligand interaction,
      indicating that the N-terminal of CXCR1 in mammals underwent more positive
      selection than that of fish. 

PMID- 24333437
TI  - C7: a CpG oligodeoxynucleotide that induces protective immune response against
      megalocytivirus in Japanese flounder (Paralichthys olivaceus) via Toll-like
      receptor 9-mediated signaling pathway.
AB  - Megalocytivirus is the causative agent of severe disease outbreaks in farmed
      fish. Currently there is no effective control against megalocytivirus in
      aquaculture. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG
      motifs are known to possess marked immunostimulatory properties. In this study,
      we investigated the potentials of ten CpG ODNs as antiviral agents in a model of
      Japanese flounder (Paralichthys olivaceus). We found that, when administered into
      flounder, three of the ten CpG ODNs inhibited viral replication in kidney,
      spleen, and liver. ODN C7, which exhibited the strongest inhibitory activity, was
      able to promote proliferation of peripheral blood leukocytes and enhance
      activation of head kidney mononuclear adherent phagocytes. When the expression of
      toll-like receptor 9 (TLR9) was knocked down in vivo by small interfering RNA, C7
      mediated immune response and antiviral activity were significantly blocked.
      Moreover, when C7 was co-administered with pCN86, a DNA vaccine against
      megalocytivirus, a significant increase in vaccine-induced protection was
      observed compared to administration with pCN86 alone. Further analysis showed
      that compared to fish immunized with pCN86, fish immunized with pCN86 plus C7
      exhibited significantly upregulated expression of a wide range of genes involved
      in innate and adaptive immunity. Taken together, these results indicate that ODN
      C7 activates TLR9-mediated immune response and possesses antiviral and adjuvant
      potentials that may be exploited for the control of megalocytivirus infection in
      farmed flounder. 

PMID- 24333438
TI  - Product formation controlled by substrate dynamics in leukotriene A4 hydrolase.
AB  - Leukotriene A4 hydrolase/aminopeptidase (LTA4H) (EC 3.3.2.6) is a bifunctional
      zinc metalloenzyme with both an epoxide hydrolase and an aminopeptidase activity.
      LTA4H from the African claw toad, Xenopus laevis (xlLTA4H) has been shown to,
      unlike the human enzyme, convert LTA4 to two enzymatic metabolites, LTB4 and
      another biologically active product Delta(6)-trans-Delta(8)-cis-LTB4 (5(S),12R
      dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid). In order to study the
      molecular aspect of the formation of this product we have characterized the
      structure and function of xlLTA4H. We solved the structure of xlLTA4H to a
      resolution of 2.3A. It is a dimeric structure where each monomer has three
      domains with the active site in between the domains, similar as to the human
      structure. An important difference between the human and amphibian enzyme is the
      phenylalanine to tyrosine exchange at position 375. Our studies show that
      mutating F375 in xlLTA4H to tyrosine abolishes the formation of the LTB4 isomeric
      product Delta(6)-trans-Delta(8)-cis-LTB4. In an attempt to understand how one
      amino acid exchange leads to a new product profile as seen in the xlLTA4H, we
      performed a conformer analysis of the triene part of the substrate LTA4. Our
      results show that the Boltzmann distribution of substrate conformers correlates
      with the observed distribution of products. We suggest that the observed
      difference in product profile between the human and the xlLTA4H arises from
      different level of discrimination between substrate LTA4 conformers. 

PMID- 24333439
TI  - Novel nuclear markers inform the systematics and the evolution of serpentine use
      in Streptanthus and allies (Thelypodieae, Brassicaceae).
AB  - Streptanthus is a genus of ca. 35 species in the tribe Thelypodieae
      (Brassicaceae) that has remarkable morphological and ecological diversity, a
      large number of species in the group being edaphic specialists endemic to unusual
      soils such as serpentine. While ecological research has shed some light on
      adaptation to serpentine in Streptanthus, there have been few insights on the
      origins and evolution of serpentine tolerance in this group, largely due to
      limited success in resolving the phylogenetic relationships among Streptanthus
      and allied genera of the Thelypodieae (Streptanthoid complex). We present a well
      resolved phylogenetic hypothesis for the Streptanthoid complex, based on three
      newly identified and highly variable single copy nuclear regions (AT4G34700,
      AT1G61620, and AT1G56590, and three others that are widely used (ITS, phyA, and
      PEPC). We also include data for two chloroplast regions (trnL and trnH-psbA).
      Collectively, our new markers provide 75% of the nuclear parsimony informative
      characters in our data. Taxonomically, our sampling is the most inclusive of any
      study of the Streptanthoid Complex to date, including 46 out of the 53 species of
      Streptanthus and Caulanthus, as well as representatives of several closely allied
      genera in the Thelypodieae. Our results reveal that Streptanthus, Caulanthus, and
      Thelypodium are not reciprocally monophyletic as currently defined. The species
      of Streptanthus form two rather distantly related clades. One clade (SC-I) is
      comprised of species with bilateral flowers and urn-shaped calyces that occur
      mainly within the California Floristic Province (CFP) hotspot; the other clade
      (SC-II) is composed of species with extant ranges mainly outside the CFP. Our
      data indicate that serpentine tolerance has evolved between eight and ten times
      in this group, of which between four and five have resulted in endemism. While
      serpentine endemism has been rarely lost, large and diverse clades composed
      mainly of serpentine endemics indicate that serpentine endemics in this group are
      more than mere 'dead-ends'.

PMID- 24333440
TI  - The essential role of clathrin-mediated endocytosis in yellow head virus
      propagation in the black tiger shrimp Penaeus monodon.
AB  - Yellow head virus (YHV) is one of the most widespread viruses seriously affecting
      black tiger shrimp (Penaeus monodon) cultivation. A previous microarray study
      demonstrated that clathrin coat assembly protein 17 (AP17) was significantly up
      regulated after YHV infection (Pongsomboon et al., 2011). Clathrin coat AP17 is a
      part of the assembly protein sigma2 (AP-2) complex which is involved in clathrin
      mediated endocytosis. Quantitative RT-PCR (qRT-PCR) revealed that the clathrin
      coat AP17 gene was up-regulated 3-fold at 12 h post YHV infection. In addition,
      immunofluorescence microscopy showed that clathrin coat AP17 was highly expressed
      in the cytoplasm of the YHV-infected hemocytes. Knockdown of the clathrin coat
      AP17 gene dramatically reduced YHV replicativity by 32-fold. Interestingly,
      shrimp pre-treated with chlorpromazine, a commercial drug that inhibits clathrin
      dependent endocytosis, exhibited significantly low levels of YHV infection. Taken
      together, these results suggest that clathrin-mediated endocytosis is involved in
      YHV propagation in P. monodon.

PMID- 24333441
TI  - SRP gene is required for Helicoverpa armigera prophenoloxidase activation and
      nodulation response.
AB  - SRP gene was first identified from the fall webworm, Hyphantria cunea as one of
      genes up-regulated after bacteria injection. A rent study in Spodoptera litura
      showed that stress-induced elevation of SRP expression highly correlates with
      reduced feeding activities and growth retardation of larvae. In this study, we
      identified a SRP gene from the cotton bollworm, Helicoverpa armigera, namely Ha
      SRP, and studied its precise roles in insect immunity. Expressions of Ha-SRP were
      upregulated in H. armigera larval hemocytes after injection of Escherichia coli.
      When the expression of Ha-SRP in H. armigera larval hemocytes was inhibited by
      dsHa-SRP injection, the transcription of prophenoloxidase genes in hemocytes was
      repressed, phenoloxidase activity in bacteria-challenged larval hemolymph was
      significantly decreased, and nodule formation in bacteria-injected larvae was
      reduced. More importantly, RNAi-treated insects infected with E. coli showed
      higher bacterial growth in hemolymph compared with infected controls. These
      results suggest that Ha-SRP gene plays importance roles in H. armigera innate
      immunity, possibly by mediating prophenoloxidase activation and nodulation
      response. 

PMID- 24333442
TI  - Indatraline inhibits Rho- and calcium-mediated glioblastoma cell motility and
      angiogenesis.
AB  - Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor
      of the central nervous system (CNS). As an attempt to identify drugs for GBM
      therapeutics, phenotypic assays were used to screen 1000 chemicals from a
      clinical compound library. GBM subtypes exhibited different capabilities to
      induce angiogenesis when cultured on Matrigel; proneural cells migrated and
      formed a tube-like structure without endothelial cells. Among the compounds
      screened, indatraline, a nonselective monoamine transporter inhibitor, suppressed
      these morphological changes; it dose dependently inhibited cell spreading,
      migration, and in vitro/in vivo tube formation. In addition to intracellular
      calcium concentration, indatraline increased the level of Rho GTPase and its
      activity. Moreover, indatraline downregulated angiogenesis-related genes such as
      IGFBP2, PTN, VEGFA, PDGFRA, and VEGFR as well as nestin, a stem cell marker.
      These findings collectively suggest that the activation of Rho GTPase and the
      suppression of angiogenesis-related factors mediate the antiangiogenic activity
      of indatraline in proneural GBM culture. 

PMID- 24333443
TI  - Akt-independent GSK3 inactivation downstream of PI3K signaling regulates
      mammalian axon regeneration.
AB  - Inactivation of glycogen synthase kinase 3 (GSK3) has been shown to mediate axon
      growth during development and regeneration. Phosphorylation of GSK3 by the kinase
      Akt is well known to be the major mechanism by which GSK3 is inactivated.
      However, whether such regulatory mechanism of GSK3 inactivation is used in
      neurons to control axon growth has not been directly studied. Here by using GSK3
      mutant mice, in which GSK3 is insensitive to Akt-mediated inactivation, we show
      that sensory axons regenerate normally in vitro and in vivo after peripheral
      axotomy. We also find that GSK3 in sensory neurons of the mutant mice is still
      inactivated in response to peripheral axotomy and such inactivation is required
      for sensory axon regeneration. Lastly, we provide evidence that GSK3 activity is
      negatively regulated by PI3K signaling in the mutant mice upon peripheral
      axotomy, and the PI3K-GSK3 pathway is functionally required for sensory axon
      regeneration. Together, these results indicate that in response to peripheral
      nerve injury GSK3 inactivation, regulated by an alternative mechanism independent
      of Akt-mediated phosphorylation, controls sensory axon regeneration. 

PMID- 24333444
TI  - Mechanisms underlying hypertriglyceridemia in rats with monosodium L-glutamate
      induced obesity: evidence of XBP-1/PDI/MTP axis activation.
AB  - Non-alcoholic fatty liver disease (NAFLD) is intimately associated with insulin
      resistance and hypertriglyceridemia, whereas many of the mechanisms underlying
      this association are still poorly understood. In the present study, we
      investigated the relationship between microsomal triglyceride transfer protein
      (MTP) and markers of endoplasmic reticulum (ER) stress in the liver of rats
      subjected to neonatal monosodium L-glutamate (MSG)-induced obesity. At age 120
      days old, the MSG-obese animals exhibited hyperglycemia, hypertriglyceridemia,
      insulin resistance, and liver steatosis, while the control (CTR) group did not.
      Analysis using fast protein liquid chromatography of the serum lipoproteins
      revealed that the triacylglycerol content of the very low-density lipoprotein
      (VLDL) particles was twice as high in the MSG animals compared with the CTR
      animals. The expression of ER stress markers, GRP76 and GRP94, was increased in
      the MSG rats, promoting a higher expression of X-box binding protein 1 (XBP-1),
      protein disulfide isomerase (PDI), and MTP. As the XBP-1/PDI/MTP axis has been
      suggested to represent a significant lipogenic mechanism in the liver response to
      ER stress, our data indicate that hypertriglyceridemia and liver steatosis
      occurring in the MSG rats are associated with increased MTP expression.

PMID- 24333445
TI  - A novel lysophosphatidic acid acyltransferase enzyme (LPAAT4) with a possible
      role for incorporating docosahexaenoic acid into brain glycerophospholipids.
AB  - Glycerophospholipids are important components of cellular membranes, required for
      constructing structural barriers, and for providing precursors of bioactive lipid
      mediators. Lysophosphatidic acid acyltransferases (LPAATs) are enzymes known to
      function in the de novo glycerophospholipid biosynthetic pathway (Kennedy
      pathway), using lysophosphatidic acid (LPA) and acyl-CoA to form phosphatidic
      acid (PA). Until now, three LPAATs (LPAAT1, 2, and 3) have been reported from the
      1-acyl-glycerol-3-phosphate O-acyltransferase (AGPAT) family. In this study, we
      identified a fourth LPAAT enzyme, LPAAT4, previously known as an uncharacterized
      enzyme AGPAT4 (LPAATdelta), from the AGPAT family. Although LPAAT4 was known to
      contain AGPAT motifs essential for acyltransferase activities, detailed
      biochemical properties were unknown. Here, we found that mouse LPAAT4 (mLPAAT4)
      possesses LPAAT activity with high acyl-CoA specificity for polyunsaturated fatty
      acyl-CoA, especially docosahexaenoyl-CoA (22:6-CoA, DHA-CoA). mLPAAT4 was
      distributed in many tissues, with relatively high expression in the brain, rich
      in docosahexaenoic acid (DHA, 22:6). mLPAAT4 siRNA in a neuronal cell line, Neuro
      2A, caused a decrease in LPAAT activity with 22:6-CoA, suggesting that mLPAAT4
      functions endogenously. siRNA in Neuro 2A cells caused a decrease in 18:0-22:6
      PC, whereas mLPAAT4 overexpression in Chinese hamster ovary (CHO)-K1 cells caused
      an increase in this species. Although DHA is considered to have many important
      functions for the brain, the mechanism of its incorporation into
      glycerophospholipids is unknown. LPAAT4 might have a significant role for
      maintaining DHA in neural membranes. Identification of LPAAT4 will possibly
      contribute to understanding the regulation and the biological roles of DHA
      containing glycerophospholipids in the brain. 

PMID- 24333446
TI  - Analysis of the stem cell characteristics of adult stem cells from Arbas white
      Cashmere goat.
AB  - Studies have shown that multipotent adult stem cells possess differentiation
      characteristics similar to embryonic stem cells and pluripotent stem cells. We
      aimed to explore these similarities further by examining the expression of the
      pluripotency and stemness biomarkers, AKP, IL-6, Nanog, Oct-4, Rex-1, Sox-2 and
      TERT, as well as the triploblastic biomarkers, Sox-1, Myod1 and Gata-6 in adipose
      derived stem cells (ADSCs), bone marrow stem cells (BMSCs) and muscle-derived
      satellite cells (MDSCs). These were isolated from adult Arbas white Cashmere
      goats and cultured in vitro. Immunocytochemistry, reverse transcription
      quantitative PCR and Western blotting were used to analyze the protein and mRNA
      expression of the markers. To investigate the ability of ADSCs, BMSCs and MDSCs
      to differentiate and cause tumors in vivo they were injected into immunodeficient
      mice (NOD-SCID). All results were compared to those for mouse embryonic stem
      cells (mESCs). Immunocytochemistry showed that AKP, IL-6, Nanog, Oct-4, Rex-1 and
      TERT were expressed in ADSCs, BMSCs and MDSCs, whereas Sox-2 was not. In ADSCs,
      the expression of IL-6 mRNA was relatively high, followed by Nanog and Oct-4,
      while Rex-1 and TERT expression were the lowest (P<0.01). In BMSCs, the
      expression of Rex-1 was relatively high, followed by IL-6, while Oct-4, Nanog and
      TERT were comparatively low (P<0.01). In MDSCs, the expression of IL-6, Nanog and
      Oct-4 were relatively high, while TERT was comparatively low (P<0.01). However,
      no expression of Sox-2 mRNA was detected in any of the three cell lines. The
      expression of Sox-1, Myod1 and Gata-6 was observed to different degrees in all
      three cell lines (P<0.01); the expression pattern in MDSCs was different from
      that in ADSCs and BMSCs. Western blotting indicated that no expression of Sox-2
      and Rex-1 protein occurred in ADSCs, BMSCs and MDSCs, while the other five
      proteins were all expressed to different degrees (P<0.01); the expression pattern
      was consistent with the mRNA results. In contrast to the mESCs, no teratoma
      tissue or triploblastic differentiation appendages were formed in the
      immunodeficient mice after injection of ADSCs, BMSCs and MDSCs. Our results
      suggest that the three adult goat stem cell types are non-oncogenic and have
      stemness characteristics similar to embryonic stem cells. Of these, MDSCs were
      found to exhibit the most ESC-like properties and would make the best candidates
      for clinical application. 

PMID- 24333447
TI  - Prostaglandin receptor EP1-mediated differential degradation of cyclooxygenases
      involves a specific lysine residue.
AB  - The cyclooxygenase (COX) enzyme isoforms COX-1 and COX-2 catalyze the main step
      in the generation of prostanoids that mediate major physiological functions.
      Whereas COX-1 is a ubiquitously expressed stable protein, COX-2 is transiently
      upregulated in many pathologies and is often associated with a poor prognostic
      outcome. We have recently shown that an interaction of COX-2 with the
      prostaglandin EP1 receptor accelerates its degradation via a mechanism that
      augments its level of ubiquitination. Here we show that the sensitivity of both
      COX-1 and COX-2 to EP1 is altered upon modification of one lysine residue. A
      point mutation of lysine to-arginine in position 432 of COX-2 (K432R) yields an
      enzyme with decreased sensitivity to EP1 -mediated degradation. In contrast,
      insertion of a putative ubiquitination site into the corresponding position of
      COX-1 (H446K') yields an enzyme with higher levels of ubiquitination and reduced
      expression. Furthermore, compared to wild type COX-1, H446K' is significantly
      more sensitive to downregulation by EP1 . Together these data suggest that
      distinctive ubiquitination of COX-1 and COX-2 may be responsible for their
      different sensitivity to EP1 -mediated degradation.

PMID- 24333448
TI  - Inhibition of protein synthesis and JNK activation are not required for cell
      death induced by anisomycin and anisomycin analogues.
AB  - Anisomycin was identified in a screen of clinical compounds as a drug that kills
      breast cancer cells (MDA16 cells, derived from the triple negative breast cancer
      cell line, MDA-MB-468) that express high levels of an efflux pump, ABCB1. We show
      the MDA16 cells died by a caspase-independent mechanism, while MDA-MB-468 cells
      died by apoptosis. There was no correlation between cell death and either protein
      synthesis or JNK activation, which had previously been implicated in anisomycin
      induced cell death. In addition, anisomycin analogues that did not inhibit
      protein synthesis or activate JNK retained the ability to induce cell death.
      These data suggest that either a ribosome-ANS complex is a death signal in the
      absence of JNK activation or ANS kills cells by binding to an as yet unidentified
      target. 

PMID- 24333449
TI  - Glucocorticoid dexamethasone regulates the differentiation of mouse conducting
      airway epithelial progenitor cells.
AB  - Inhaled glucocorticoid dexamethasone is the most effective treatment of asthma
      currently available. Epithelial damage and shedding represents a clear
      manifestation of asthmatic pathologies. However it remains unknown if
      dexamethasone regulates functions of airway progenitor cells that are responsible
      for epithelial repair. In present study Secretoglobin1a1 (Scgb1a1) lineage
      tracing mice were injected intraperitoneally with tamoxifen to induce the
      expression of green fluorescence protein (GFP) in Scgb1a1-expressing conducting
      airway progenitor cells. Scgb1a1-expressing progenitor cells were isolated from
      lungs of Scgb1a1 lineage tracing mice via flow activated cell sorting. In vitro
      three-dimensional matrigel culture of these progenitor cells revealed that
      dexamethasone has little effect on the colony forming ability of airway
      epithelial progenitor cells, but exhibits significant effects on the
      differentiation of the progenitor cells. Compared to the untreated group,
      dexamethasone treatment inhibited the expression of forkhead box J1 (FoxJ1) and
      mucin subtype A & C (Muc5Ac), but promoted the expression of calcium activated
      chloride channel 3 (Clca3) and cystic fibrosis transmembrane conductance
      regulator (Cftr). Dexamethasone-induced effects on the expression of FoxJ1,
      Muc5Ac and Clca3 were abolished or even reversed in the presence of RU486, an
      antagonist of glucocorticoid receptor, indicating that glucocorticoid receptor
      plays a role in the regulation of airway epithelial progenitor cells by
      dexamethasone. These data suggested that, though effective to reduce airway
      inflammation, dexamethasone treatment alone fails to fully restore the
      mucociliary clearance function in the treatment of asthma patients. 

PMID- 24333450
TI  - In vitro investigation of coupling-agent-free dental restorative composite based
      on nano-porous alumina fillers.
AB  - OBJECTIVES: The study aims at demonstrating the feasibility of a novel type of
      coupling-agent-free resin composite based on nano-porous fillers. METHODS: The
      fillers were obtained by ball-milling anodic alumina membranes. Composites were
      prepared with standard resin at maximum loading of 50% by weight. The resin
      matrix penetration into the pores was verified visually by scanning electron
      microscopy and mechanically by atomic force microscopy in force modulation mode.
      The dynamic flexural modulus at 1Hz was measured by dynamic mechanical analysis.
      Silver nanoparticles were also synthesized in the pores and their release was
      investigated with inductive coupled plasma optical emission spectrometry.
      RESULTS: A storage modulus of 5GPa was measured, similar to the ~6GPa ones of two
      coupling-agent-based dental restorative composites used for comparison, which is
      a promising starting point, additionally showing better one-year equivalent
      ageing as compared to both commercial materials. Loading the pores with silver
      nanoparticles was demonstrated as well as their subsequent release in a model
      system. SIGNIFICANCE: The alumina micro-particles with interconnected nano-pores
      allow mechanical interlocking between fillers and matrix without the need for
      chemical bonding. This material is also promising for being made bio-active,
      after pore filling with different agents.

PMID- 24333451
TI  - Impact of surfactants on the crystal growth of amorphous celecoxib.
AB  - The purpose of this study was to investigate the impact of surfactants on the
      rate of crystal growth of amorphous celecoxib, both in the presence and absence
      of a polymer. Celecoxib is a poorly water-soluble non-steroidal anti-inflammatory
      drug. Such compounds may be formulated as amorphous solid dispersions to improve
      bioavailability, and solid dispersions can contain both a surfactant and a
      polymer. While the impact of polymers on crystal growth rates has been studied,
      the effect of surfactants is largely unexplored. Herein, the effect of sodium
      lauryl sulfate (SLS), sucrose palmitate and d-alpha tocopherol polyethylenglycol
      1000 succinate (TPGS) at a 10% (w/w) concentration on the crystal growth rate of
      celecoxib was investigated. Linear crystal growth rates as a function of
      temperature (70-120  degrees C) were measured using optical microscopy. The
      mixtures were characterized using differential scanning calorimetry (DSC),
      infrared spectroscopy, and X-ray diffraction. The results indicate that the
      surfactants increase the crystal growth rate of amorphous celecoxib. However,
      addition of polyvinyl pyrrolidone (PVP) helped to mitigate the increase in growth
      rates, although the ternary systems were highly complex. Thus it is clear that
      the impact of a surfactant on the physical stability of an amorphous solid
      dispersion should be considered during formulation.

PMID- 24333453
TI  - Management decisions for adolescent idiopathic scoliosis significantly affect
      patient radiation exposure.
AB  - BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) patients treated before
      the 1990s have a 1% to 2% increased lifetime risk of developing breast and
      thyroid cancer as a result of ionizing radiation from plain radiographs. Although
      present plain radiographic techniques have been able to reduce some of the
      radiation exposure, modern treatment algorithms for scoliosis often include
      computed tomography (CT) and intraoperative fluoroscopy. The exact magnitude of
      exposure to ionizing radiation in adolescents during modern scoliosis treatment
      is therefore unclear. PURPOSE: To determine the difference in radiation exposures
      in patients undergoing various forms of treatment for AIS. STUDY DESIGN:
      Retrospective cohort. PATIENT SAMPLE: Patients aged 9 to 18 years with a
      diagnosis of AIS, followed and/or treated with nonoperative or operative
      management for a minimum of 2 years. OUTCOME MEASURES: Number of radiographs and
      total radiation exposure calculated. METHODS: The charts and radiographs of
      patients managed for AIS at a single institution between September 2007 and
      January 2012 were reviewed. Patients were divided into three groups: operative
      group, braced group, and observation group. Patient demographics, Cobb angles,
      and curve types were recorded. The number of radiographs per year that each
      patient received and the total radiation dose were recorded. The plain
      radiographic radiation exposure was then combined with the direct exposure
      recording from ancillary tests, such as fluoroscopy and CT, and a radiation
      exposure rate was calculated (mrad/y). A single-factor analysis of variance
      (alpha=0.01) with a Tukey honest significant difference post hoc analysis was
      used to test significance between groups. RESULTS: Two hundred sixty-seven
      patients were evaluated: 86 operative, 80 brace, and 101 observation. All groups
      had similar demographics and curve type distribution. The mean initial Cobb angle
      at presentation was significantly different between the groups: operative (57
      degrees +/-11 degrees ), brace (24 degrees +/-7.9 degrees ), and observation (18
      degrees +/-9.4 degrees ) (p<.01). There was a significant difference among the
      groups in terms of the mean number of radiographs received per year; operative
      group, 12.2 (95% confidence interval [CI]: 10.8-13.5; p<.001); braced group, 5.7
      (95% CI: 5.2-6.2; p<.001), and observed group, 3.5 (95% CI: 3.160-3.864; p<.001).
      The operative group received 1,400 mrad per year (95% CI: 1,350-1,844; p<.001),
      braced group received 700 mrad per year (95% CI: 598-716; p<.001), and observed
      group received 400 mrad per year (95% CI: 363-444; p<.001). Importantly, 78% of
      radiation in the operative group was attributable to the operative fluoroscopy
      exposure. CONCLUSIONS: Significant differences exist in the total radiation
      exposure in scoliosis patients with different treatment regimens, with operative
      patients receiving approximately 8 to 14 times more radiation than braced
      patients or those undergoing observation alone, respectively. Operative patients
      also receive more than twice the radiation per year than braced or observed
      patients. Almost 78% of the annual radiation exposure for operative patients
      occurs intraoperatively. Because children are notably more sensitive to the
      carcinogenic effects of ionizing radiation, judicious use of present imaging
      methods and a search for newer imaging methods with limited ionizing radiation
      should be undertaken.

PMID- 24333452
TI  - Development of a vaginal delivery film containing EFdA, a novel anti-HIV
      nucleoside reverse transcriptase inhibitor.
AB  - The aim of this work was to develop a fast-dissolving film formulation containing
      EFdA for potential use as a topical vaginal microbicide for prevention of HIV
      sexual transmission. Solid state compatibility approaches were used to screen
      commonly used polymers for formulation development. Factorial design and
      desirability function were used to investigate the effect of two variables, the
      ratio of the polymers and the concentration of selected plasticizer on four
      mechanical responses including tensile strength, elongation at break, toughness
      and elastic modulus for optimization of the film formulation. Assessments of EFdA
      loaded films included physicochemical characteristics, in vitro cytotoxicity,
      epithelia integrity, ex vivo permeability and bioactivity test. The optimal
      placebo film was composed of PVA, HPMC E5 and propylene glycol (7:3:3, w/w), and
      its mechanical characteristics were comparable to those of VCF((r)) film (a
      commercial vaginal film product). Permeability studies using human ectocervical
      explants showed that there was no significant difference in cumulative permeated
      amount of EFdA between EFdA film and free EFdA. The results of in vitro
      cytotoxicity and bioactivity testing showed that 50% cytotoxic concentration
      (CC50) was several orders of magnitude higher than 50% effective concentration
      (EC50) of EFdA. Furthermore, epithelial integrity study showed that EFdA-loaded
      film had a much lower toxicity to HEC-1A cell monolayers as compared to VCF((r)).
      Therefore, EFdA-loaded vaginal film may be considered as a promising vaginal
      microbicide for HIV prevention. 

PMID- 24333454
TI  - How do we improve?

PMID- 24333455
TI  - Influence of hypotension and nerve root section on the ability to mobilize the
      spinal cord during spine surgery. An experimental study in a pig model.
AB  - BACKGROUND CONTEXT: The correction of severe spinal deformities by an isolated
      posterior approach often involves cord manipulation together with hypotensive
      anesthesia. To date, the efficiency of methods to increase the tolerance of the
      cord to displacement and the influence of hypotension on this tolerance is yet to
      be assessed. PURPOSE: The objective of this study was to determine the limits of
      cord displacement before the disappearance of neurophysiologic signals. The
      influence of the type of force applied, the section of the roots, and the induced
      hypotension on the cord's tolerance to displacement was also assessed. STUDY
      DESIGN: Experimental study using a domestic pig model. OUTCOME MEASURES:
      Successive records of cord-to-cord motor evoked potentials were obtained during
      displacement maneuvers. Displacing forces were released immediately after the
      absence of neurophysiologic signals. METHODS: Surgical procedures were performed
      under conventional general anesthesia. The spinal cord and nerve roots from T6 to
      T10 levels were exposed by excision of the posterior elements, allowing for free
      cord movement. Three groups were established according to the method of spinal
      cord displacement: the separation (Group 1, n=5), the root stump pull (Group 2,
      n=5), and the torsion groups (Group 3, n=5). An electromechanical external device
      was used to apply the displacing forces. The three displacement tests were
      repeated after sectioning the adjacent nerve roots. The experiments were first
      carried out under normotension and afterward under induced hypotension. RESULTS:
      In Group 1, evoked potential disappeared with a displacement of 10.1+/-1.6 mm
      with unharmed roots and 15.3+/-4.7 mm after the sectioning of four adjacent roots
      (p<.01). After induced hypotension, potentials were lost at 4.0+/-1.2 mm (p<.01).
      In Group 2, the absence of potentials occurred at 20.0+/-4.3 mm and increased to
      23.5+/-2.1 mm (p<.05) after cutting the two contralateral roots. Under
      hypotensive conditions, the loss of neurophysiologic signals was detected at
      5.3+/-1.2 mm (p<.01). In Group 3, the cord allowed torsion of 95.3+/-.2 degrees 
      that increased to 112.4+/-7.1 degrees  if the contralateral roots were cut. Under
      hypotension, the loss of potentials was found at 20+/-6.2 degrees  (p<.01).
      CONCLUSIONS: In this experimental model, it was possible to displace the thoracic
      spinal cord by a distance superior to the spinal cord width without suffering
      neurophysiologic changes. The limits of cord displacement increase when the
      adjacent nerve roots are sacrificed. Induced hypotension had a dramatic effect on
      the tolerance of the spinal cord for displacement. This work has an important
      clinical significance because induced hypotension during specific spine surgery
      procedures requiring spinal cord manipulation in humans may increase the risk of
      neurologic spinal cord injury.

PMID- 24333456
TI  - Revision surgery after cervical laminoplasty: report of five cases and literature
      review.
AB  - BACKGROUND CONTEXT: Revision surgery after laminoplasty is rarely performed, and
      there are few reports of this procedure in the English literature. PURPOSE: To
      evaluate the reasons why patients underwent revision surgery after laminoplasty
      and to discuss methods of preventing the need for revision surgery. A literature
      review with a comparative analysis between previous reports and present cases was
      also performed. STUDY DESIGN: Case report and literature review. PATIENT SAMPLE:
      Five patients who underwent revision surgery after laminoplasty. OUTCOME
      MEASURES: Diagnosis was based on the preoperative computed tomography and
      magnetic resonance imaging findings. Neurologic findings were evaluated using the
      Japanese Orthopedic Association score. METHODS: A total of 237 patients who
      underwent cervical laminoplasty for cervical spondylotic myelopathy from 1990 to
      2010 were reviewed. Patients with ossification of the posterior longitudinal
      ligament, renal dialysis, infection, tumor, or rheumatoid arthritis were
      excluded. Five patients who underwent revision surgery for symptoms of recurrent
      myelopathy or radiculopathy were identified, and the clinical courses and
      radiological findings of these patients were retrospectively reviewed. RESULTS:
      The average interval from the initial surgery to revision surgery was 15.0 (range
      9-19) years. The patients were four men and one woman with an average age at the
      time of the initial operation of 49.8 (range 34-65) years. Four patients
      developed symptoms of recurrent myelopathy after their initial surgery, for the
      following reasons: adjacent segment canal stenosis, restenosis after inadequate
      opening of the lamina with degenerative changes, and trauma after inadequate
      opening of the lamina. One patient developed new radiculopathy symptoms because
      of foraminal stenosis secondary to osteoarthritis at the Luschka and
      zygapophyseal joints. All patients experienced resolution of their symptoms after
      revision surgery. CONCLUSIONS: Revision surgery after laminoplasty is rare.
      Inadequate opening of the lamina is one of the important reasons for needing
      revision surgery. Degenerative changes after laminoplasty may also result in a
      need for revision surgery. Surgeons should be aware of the degenerative changes
      that can cause neurologic deterioration after laminoplasty.

PMID- 24333457
TI  - Chronic low back pain sufferers exhibit freezing-like behaviors when asked to
      move their trunk as fast as possible.
AB  - BACKGROUND CONTEXT: The effect of chronic low back pain (CLBP) on the kinematic
      parameters of trunk motion has received much more interest in this last decade.
      However, there are no descriptions of the motor strategies that occur when
      patients perform trunk movements in the three anatomical planes at different pace
      conditions. PURPOSE: To investigate motor strategies used by CLBP patients and
      asymptomatic people while performing different go and back trunk movements in an
      upright standing position. STUDY DESIGN: A comparative study. PATIENT SAMPLE: The
      control group (CG, n=33) included 14 men and 19 women with no history of low back
      pain, and the chronic low back pain group (CLBPG, n=49) included 21 men and 28
      women. OUTCOME MEASURES: Kinematic data were analyzed during six trunk movements:
      flexion, extension, left and right lateral bendings, and rotations under two pace
      conditions (preferred and fast paces). METHODS: A three-dimensional
      optoelectronic motion analysis system was used to assess static (trunk
      inclinations and base of support) and dynamic (range of motion [ROM] and mean
      angular velocity of the trunk) parameters during the go and back phases of trunk
      movements. RESULTS: In the initial position, CLBPG showed a more forward-tilted
      trunk inclination (2.1 degrees +/-1.1 degrees , p=.013) compared with CG. The
      base of support was significantly higher in CG (+22.7 cm2, p=.009) during the
      fast pace when compared with the preferred pace. Regardless of the pace
      condition, ROM and mean angular velocity of the trunk were significantly lower in
      CLBPG for all examined movements and the pace condition did not significantly
      alter ROM. At the preferred pace, both groups displayed the same motor strategy:
      they all went faster during the second phase of movement than during the first
      phase. However, at the fast pace, while CG was going faster during the first
      phase than during the second, CLBPG maintained the same motor strategy as at the
      preferred pace. CONCLUSIONS: Contrary to CG who changed its motor behavior from a
      preferred pace to a fast pace, CLBPG exhibited freezing-like behaviors. This
      original result highlights the importance of studying the velocity. The use of
      this parameter may improve the diagnosis of CLBP patients and could be a key
      indicator for treatment progress and long-term monitoring.

PMID- 24333458
TI  - Insomnia in a chronic musculoskeletal pain with disability population is
      independent of pain and depression.
AB  - BACKGROUND CONTEXT: Insomnia is frequently experienced by patients suffering from
      chronic musculoskeletal disorders but is often seen as simply a symptom of pain
      or depression and not as an independent disorder. Compared with those who
      experience only chronic pain, patients with both chronic pain and insomnia report
      higher pain intensity, more depressive symptoms, and greater distress. However,
      insomnia has not yet been systematically studied in a chronic musculoskeletal
      pain with disability population. PURPOSES: This study assessed the prevalence and
      severity of patient-reported insomnia, as well as the relationship among
      insomnia, pain intensity, and depressive symptoms, in a chronic musculoskeletal
      pain with disability population. STUDY DESIGN/SETTING: This was a retrospective
      study of prospectively captured data. PATIENT SAMPLE: A consecutive cohort of 326
      chronic musculoskeletal pain with disability patients (85% with spinal injuries)
      entered a functional restoration treatment program. All patients signed a consent
      form to participate in this protocol. OUTCOME MEASURES: Insomnia was assessed
      with the Insomnia Severity Index, a validated patient-report measure of insomnia
      symptoms. Four patient groups were formed: no clinically significant insomnia
      (score, 0-7); subthreshold insomnia (score, 8-14); moderate clinical insomnia
      (score, 15-21); and severe clinical insomnia (score, 22-28). Three patterns of
      sleep disturbance were also evaluated: early, middle, and late insomnia.
      Additional validated psychosocial patient-reported data were collected, including
      the Pain Visual Analog Scale, the Beck Depression Inventory, the Oswestry
      Disability Index, and the Pain Disability Questionnaire. METHODS: Patients
      completed a standard psychosocial assessment battery on admission to the
      functional restoration program. The program included a quantitatively directed
      exercise process in conjunction with a multimodal disability management approach.
      The four insomnia groups were compared on demographic and psychosocial variables.
      The shared variances among insomnia, depression, and pain were determined by
      partial correlational analyses. RESULTS: The presence of no clinically
      significant insomnia, subthreshold insomnia, moderate clinical insomnia, and
      severe clinical insomnia was found in 5.5%, 21.2%, 39.6%, and 33.7% of the
      cohort, respectively. More than 70% of patients reported moderate to severe
      insomnia symptoms, which is a considerably higher prevalence than that found in
      most patient cohorts studied previously. A stepwise pattern was found, in which
      severe clinical insomnia patients reported the highest pain, the most severe
      depressive symptoms, and the greatest disability. The severe clinical insomnia
      patients also reported a higher number of sleep disturbance types (early, middle,
      and late insomnia) than the other three groups. In fact, 62.9% of them reported
      all three disturbance types. Although correlations were found between insomnia
      and depressive symptoms and between insomnia and pain, the shared variances were
      small (12.9% and 3.6%, respectively), indicating that depression and pain are
      separate constructs from insomnia. CONCLUSION: This research indicates that
      insomnia is a significant and pervasive problem in a chronic musculoskeletal pain
      with disability population. Most importantly, although insomnia has traditionally
      been assumed to be simply a symptom of pain or depression, the findings of the
      present study reveal that it is a construct relatively independent from both pain
      and depression. Specific insomnia assessment and treatment is therefore
      recommended for this chronic musculoskeletal pain with disability population.

PMID- 24333459
TI  - Comparison of complications, costs, and length of stay of three different lumbar
      interbody fusion techniques: an analysis of the Nationwide Inpatient Sample
      database.
AB  - BACKGROUND CONTEXT: Lumbar interbody fusion (LIF) techniques have been used for
      years to treat a number of pathologies of the lower back. These procedures may
      use an anterior, posterior, or combined surgical approach. Each approach is
      associated with a unique set of complications, but the exact prevalence of
      complications associated with each approach remains unclear. PURPOSE: To
      investigate the rates of perioperative complications of anterior lumbar interbody
      fusion (ALIF), posterior/transforaminal lumbar interbody fusion (P/TLIF), and LIF
      with a combined anterior-posterior interbody fusion (APF). STUDY DESIGN/SETTING:
      Retrospective review of national data from a large administrative database.
      PATIENT SAMPLE: Patients undergoing ALIF, P/TLIF, or APF. OUTCOME MEASURES:
      Perioperative complications, length of stay (LOS), total costs, and mortality.
      METHODS: The Nationwide Inpatient Sample database was queried for patients
      undergoing ALIF, P/TLIF, or APF between 2001 and 2010 as identified via
      International Classification of Diseases, ninth revision codes. Univariate
      analyses were carried out comparing the three cohorts in terms of the outcomes of
      interest. Multivariate analysis for primary outcomes was carried out adjusting
      for overall comorbidity burden, race, gender, age, and length of fusion. National
      estimates of annual total number of procedures were calculated based on the
      provided discharge weights. Geographic distribution of the three cohorts was also
      investigated. RESULTS: An estimated total of 923,038 LIFs were performed between
      2001 and 2010 in the United States. Posterior/transforaminal lumbar interbody
      fusions accounted for 79% to 86% of total LIFs between 2001 and 2010, ALIFs for
      10% to 15%, and APF decreased from 10% in 2002 to less than 1% in 2010. On
      average, P/TLIF patients were oldest (54.55 years), followed by combined approach
      (47.23 years) and ALIF (46.94 years) patients (p<.0001). Anterior lumbar
      interbody fusion, P/TLIF, and combined surgical costs were $75,872, $65,894, and
      $92,249, respectively (p<.0001). Patients in the P/TLIF cohort had the greatest
      number of comorbidities, having the highest prevalence for 10 of 17 comorbidities
      investigated. Anterior-posterior interbody fusion group was associated with the
      greatest number of complications, having the highest incidence of 12 of the 16
      complications investigated. CONCLUSIONS: These data help to define the
      perioperative risks for several LIF approaches. Comparison of outcomes showed
      that a combined approach is more expensive and associated with greater LOS,
      whereas ALIF is associated with the highest postoperative mortality. These trends
      should be taken into consideration during surgical planning to improve clinical
      outcomes.

PMID- 24333460
TI  - Kinematics of the thoracic spine in trunk lateral bending: in vivo three
      dimensional analysis.
AB  - BACKGROUND CONTEXT: In vivo three-dimensional kinematics of the thoracic spine in
      trunk lateral bending with an intact rib cage and soft tissues has not been well
      documented. There is no quantitative data in the literature for lateral bending
      in consecutive thoracic spinal segments, and there has not been consensus on the
      patterns of coupled motion with lateral bending. PURPOSE: To demonstrate
      segmental ranges of motion (ROMs) in lateral bending and coupled motions of the
      thoracic spine. STUDY DESIGN: In vivo three-dimensional biomechanics study of the
      thoracic spine. PATIENT SAMPLE: Fifteen healthy male volunteers. OUTCOME
      MEASURES: Computed analysis by using voxel-based registration. METHODS:
      Participants underwent computed tomography of the thoracic spine in three supine
      positions: neutral, right maximum lateral bending, and left maximum lateral
      bending. The relative motions of vertebrae were calculated by automatically
      superimposing an image of vertebrae in a neutral position over images in bending
      positions, using voxel-based registration. Mean values of lateral bending were
      compared among the upper (T1-T2 to T3-T4), the middle-upper (T4-T5 to T6-T7), the
      middle-lower (T7-T8 to T9-T10), and the lower (T10-T11 to T12-L1) parts of the
      spine. RESULTS: At lateral bending, the mean ROM (+/-standard deviation) of T1
      with respect to L1 was 15.6 degrees +/-6.3 degrees  for lateral bending and 6.2
      degrees +/-4.8 degrees  for coupled axial rotation in the same direction as
      lateral bending. The mean lateral bending of each spinal segment with respect to
      the inferior adjacent vertebra was 1.4 degrees +/-1.3 degrees  at T1-T2, 1.3
      degrees +/-1.2 degrees  at T2-T3, 1.4 degrees +/-1.3 degrees  at T3-T4, 0.9
      degrees +/-0.9 degrees  at T4-T5, 0.8 degrees +/-1.0 degrees  at T5-T6, 1.1
      degrees +/-1.1 degrees  at T6-T7, 1.7 degrees +/-1.2 degrees  at T7-T8, 1.3
      degrees +/-1.2 degrees  at T8-T9, 1.6 degrees +/-0.7 degrees  at T9-T10, 1.8
      degrees +/-0.8 degrees  at T10-T11, 2.3 degrees +/-1.0 degrees  at T11-T12, and
      2.2 degrees +/-0.8 degrees  at T12-L1. The smallest and the largest amounts of
      lateral bending were observed in the middle-upper and the lower parts,
      respectively. There was no significant difference in lateral bending between the
      upper and the middle-lower parts. Coupled axial rotation of each segment was
      generally observed in the same direction as lateral bending. However, high
      variability was found at the T2-T3 to T5-T6 segments. Coupled flexion was
      observed at the upper and middle parts, and coupled extension was observed at the
      lower part. CONCLUSIONS: This study revealed in vivo three-dimensional motions of
      consecutive thoracic spinal segments in trunk lateral bending. The thoracolumbar
      segments significantly contributed to lateral bending. Coupled axial rotation
      generally occurred in the same direction with lateral bending. However, more
      variability was observed in the direction of coupled axial rotation at T2-T3 to
      T5-T6 segments in the supine position. These results are useful for understanding
      normal kinematics of the thoracic spine.

PMID- 24333461
TI  - Digital mRNA profiling of N-glycosylation gene expression in recombinant Chinese
      hamster ovary cells treated with sodium butyrate.
AB  - To understand the effects of sodium butyrate (NaBu) on protein glycosylation,
      recombinant Chinese hamster ovary (rCHO) cells producing Fc-fusion glycoprotein
      were subjected to 3mM NaBu. The addition of NaBu to the cultures reduced the
      relative proportion of acidic isoforms and sialic acid content of the
      glycoprotein. Fifty-two N-glycosylation-related gene expressions were also
      assessed by the NanoString nCounter system, which can provide a direct digital
      readout using custom-designed color-coded probes. Among them, ten genes (ugp,
      slc35a2, ganc, man1a, man1c, mgat5a, st3gal5, glb1, neu1, and neu3) were up
      regulated and three genes (b4galt2, st3gal3, and neu2) were down-regulated
      significantly. Altered expression patterns in st3gal3, neu1, and neu3, which have
      roles in the sialic acid biosynthesis pathway, correlated with reduced sialic
      acid content of the glycoprotein by NaBu. Taken together, the results obtained in
      this study provide a better understanding of the detrimental effect of NaBu on N
      glycosylation in rCHO cells. 

PMID- 24333462
TI  - Analysis of the kinetics of lipid peroxidation in terms of characteristic time
      points.
AB  - Measuring peroxidation of aggregated lipids in model systems (liposomes,
      micelles, emulsions or microemulsions) as well as in samples of biological origin
      ex vivo (isolated lipoproteins, blood sera or plasma) is widely used in medical
      and biological investigations, to evaluate the oxidative stress, antioxidants'
      efficiency and lipid oxidizability in different pathophysiological states. To
      avoid possible artifacts, such investigations must be based on the time course of
      peroxidation (i.e. on kinetic studies). To be able to compare complex kinetic
      profiles, it is important to characterize them in terms of mechanistically
      meaningful and experimentally unequivocal parameters. In this review, we
      characterize the typically observed continuous kinetic profiles in terms of a
      limited number of characteristic time-points (both commonly used and additional
      time-points and their combinations) that can be derived from experimental time
      dependencies. The meaning of each of the experimentally observed characteristic
      parameters is presented in terms of rate constants and concentrations, derived on
      the basis of mechanistic considerations. Theoretical expressions for these
      characteristic parameters are based on a model that includes both the inhibited
      peroxidation and the uninhibited peroxidation occurring after consumption of the
      antioxidant(s). Comparison between theoretically predicted dependencies and
      experimental data support our treatment considered with special emphasis on
      transition metals-induced peroxidation of lipoproteins. 

PMID- 24333463
TI  - Multiplex and functional detection of antigen-specific human T cells by ITRA-
      indirect T cell recognition assay.
AB  - The identification and functional characterization of pathogen-specific T cells
      plays a critical role in immunological research and diagnostics. In addition to
      the present standard technologies such as intracellular cytokine staining (ICS),
      enzyme-linked immunospot (ELISPOT) and peptide-major-histocompatibility-complex
      (MHC) multimer staining, we aimed to develop a multiplex detection assay, which
      provides fast in vitro functional data for both human CD4 and CD8 T cells with
      different antigen specificities in one sample. In this study, we have exploited
      the expression of CD83 on B cells to develop the cell array-based indirect T cell
      recognition assay (ITRA). In detail, B cells are pulsed with different pathogen
      peptide pools and fluorescently barcoded. Thereafter the B cells are pooled and
      co-cultured with autologous T cells. Subsequently each B cell population is
      analyzed via flow cytometry for CD83 expression, which indicates antigen-specific
      interaction with CD4 T cells. Moreover, we revealed donor dependent variations of
      cytotoxic activity of pathogen-specific CD4 T cells and CD8 T cells, evidenced by
      specific lysis of peptide-pulsed B cells. Taken together, ITRA is a novel antigen
      presenting cell (APC) array based method to analyze the presence and function of
      various antigen-specific T cells in one sample. It has the potential to be used
      in the future for epitope/antigen screening in research and for analysis of anti
      tumor, anti-pathogen or autoimmune T cell responses in patient samples. 

PMID- 24333464
TI  - Automatic perceptual simulation of first language meanings during second language
      sentence processing in bilinguals.
AB  - Research supports the claim that, when understanding language, people perform
      mental simulation using those parts of the brain which support sensation, action,
      and emotion. A major criticism of the findings quoted as evidence for embodied
      simulation, however, is that they could be a result of conscious image generation
      strategies. Here we exploit the well-known fact that bilinguals routinely and
      automatically activate both their languages during comprehension to test whether
      this automatic process is, in turn, modulated by embodied simulatory processes.
      Dutch participants heard English sentences containing interlingual homophones and
      implying specific distance relations, and had to subsequently respond to pictures
      of objects matching or mismatching this implied distance. Participants were
      significantly slower to reject critical items when their perceptual features
      matched said distance relationship. These results suggest that bilinguals not
      only activate task-irrelevant meanings of interlingual homophones, but also
      automatically simulate these meanings in a detailed perceptual fashion. Our study
      supports the claim that embodied simulation is not due to participants' conscious
      strategies, but is an automatic component of meaning construction. 

PMID- 24333465
TI  - Managing heavy metal toxicity stress in plants: biological and biotechnological
      tools.
AB  - The maintenance of ion homeostasis in plant cells is a fundamental physiological
      requirement for sustainable plant growth, development and production. Plants
      exposed to high concentrations of heavy metals must respond in order to avoid the
      deleterious effects of heavy metal toxicity at the structural, physiological and
      molecular levels. Plant strategies for coping with heavy metal toxicity are
      genotype-specific and, at least to some extent, modulated by environmental
      conditions. There is considerable interest in the mechanisms underpinning plant
      metal tolerance, a complex process that enables plants to survive metal ion
      stress and adapt to maintain growth and development without exhibiting symptoms
      of toxicity. This review briefly summarizes some recent cell biological,
      molecular and proteomic findings concerning the responses of plant roots to heavy
      metal ions in the rhizosphere, metal ion-induced reactions at the cell wall
      plasma membrane interface, and various aspects of heavy metal ion uptake and
      transport in plants via membrane transporters. The molecular and genetic
      approaches that are discussed are analyzed in the context of their potential
      practical applications in biotechnological approaches for engineering increased
      heavy metal tolerance in crops and other useful plants. 

PMID- 24333466
TI  - Impact of isomalathion on malathion cytotoxicity and genotoxicity in human HepaRG
      cells.
AB  - Isomalathion is a major impurity of technical grade malathion, one of the most
      abundantly applied insecticides; however little is known about its
      hepatotoxicity. In the present study, cytotoxicity and genotoxicity of malathion
      and isomalathion either individually or in combination, were assessed using the
      metabolically competent human liver HepaRG cell line. Isomalathion reduced cell
      viability starting at a 100 MUM concentration after a 24h exposure. It also
      significantly induced caspase-3 activity in a dose-dependent manner starting at 5
      MUM. On the contrary, even at concentrations as high as 500 MUM malathion
      affected neither cell viability nor caspase-3 activity. Moreover, co-exposure of
      both compounds resulted in decreased toxicity of isomalathion. By contrast,
      malathion and isomalathion either separately or in combination, slightly induced
      micronuclei formation at low concentrations and had additive genotoxic effects
      when combined at 25 MUM. Individually or combined isomalathion directly inhibited
      activity of carboxyesterases which are involved in detoxication of malathion. In
      addition, transcripts of CYP2B6 and CYP3A4, two CYPs responsible for malathion
      phase I metabolism, were strongly induced by the mixture while isomalathion alone
      only moderately decreased CYP1A2 and increased CYP2B6 transcripts. However, these
      CYPs were not altered at the protein or activity levels. Taken altogether, our
      results showed that isomalathion was much more cytotoxic than malathion while
      both compounds had comparable genotoxic effects in HepaRG hepatocytes at low
      concentrations and brought further support to the importance of considering
      impurities and interactions during evaluation of health risks of pesticides.

PMID- 24333467
TI  - Vestibular damage in chronic ototoxicity: a mini-review.
AB  - Ototoxicity is a major cause of the loss of hearing and balance in humans.
      Ototoxic compounds include pharmaceuticals such as aminoglycoside antibiotics,
      anti-malarial drugs, loop diuretics and chemotherapeutic platinum agents, and
      industrial chemicals including several solvents and nitriles. Human and rodent
      data indicate that the main target of toxicity is hair cells (HCs), which are the
      mechanosensory cells responsible for sensory transduction in both the auditory
      and the vestibular system. Nevertheless, the compounds may also affect the
      auditory and vestibular ganglion neurons. Exposure to ototoxic compounds has been
      found to cause HC apoptosis, HC necrosis, and damage to the afferent terminals,
      of differing severity depending on the ototoxicity model. One major pathway
      frequently involved in HC apoptosis is the c-jun N-terminal kinase (JNK)
      signaling pathway activated by reactive oxygen species, but other apoptotic
      pathways can also play a role in ototoxicity. Moreover, little is known about the
      effects of chronic low-dose exposure. In rodent vestibular epithelia, extrusion
      of live HCs from the sensory epithelium may be the predominant form of cell
      demise during chronic ototoxicity. In addition, greater involvement of the
      afferent terminals may occur, particularly the calyx units contacting type I
      vestibular HCs. As glutamate is the neurotransmitter in this synapse, excitotoxic
      phenomena may participate in afferent and ganglion neuron damage. Better
      knowledge of the events that take place in chronic ototoxicity is of great
      interest, as it will increase understanding of the sensory loss associated with
      chronic exposure and aging. 

PMID- 24333468
TI  - Expression of claudin-7 and loss of claudin-18 correlate with poor prognosis in
      gastric cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the expression of claudin
      3, claudin-7, and claudin-18 in gastric cancer and to determine the significance
      of these proteins for patient outcome. MATERIALS AND METHODS: A total of 134
      samples were obtained from surgically resected specimens from patients who were
      diagnosed with gastric carcinoma at a single institution. Paraffin tissue
      sections from tissue microarray blocks were examined with immunohistochemistry
      for the expression of claudin-3, claudin-7, and claudin-18. RESULTS: In normal
      gastric tissues, positive immunoreactivity was detected for claudin-18 but not
      for claudin-3 or claudin-7. Claudin-3 and claudin-7 were expressed in 25.4% and
      29.9% of the gastric cancer tissues, respectively. However, 51.5% of gastric
      cancer tissues exhibited reduced expression of claudin-18. Claudin-7 expression
      was significantly lower in cases with diffuse histologic type and positive
      lymphatic invasion. There was a significant inverse correlation between claudin
      18 expression and perineural invasion. In the survival analysis, the overall
      survival time was shorter in patients with claudin-7 expression than in those
      without claudin-7 expression. However, the overall survival was longer in
      patients with claudin-18 expression than in those without claudin-18 expression.
      CONCLUSIONS: Our data suggest that the up-regulation of claudin-3 and claudin-7
      and the down-regulation of claudin-18 may play a role in the carcinogenesis of
      gastric cancer. Furthermore, the expression of claudin-7 and the loss of claudin
      18 may be independent indicators of a poor prognosis in patients with gastric
      cancer.

PMID- 24333469
TI  - Variability in facial palsy service provisioning in the United Kingdom.

PMID- 24333470
TI  - A non-parametric Bayesian approach for clustering and tracking non-stationarities
      of neural spikes.
AB  - BACKGROUND: Neural spikes from multiple neurons recorded in a multi-unit signal
      are usually separated by clustering. Drifts in the position of the recording
      electrode relative to the neurons over time cause gradual changes in the position
      and shapes of the clusters, challenging the clustering task. By dividing the data
      into short time intervals, Bayesian tracking of the clusters based on Gaussian
      cluster model has been previously proposed. However, the Gaussian cluster model
      is often not verified for neural spikes. NEW METHOD: We present a Bayesian
      clustering approach that makes no assumptions on the distribution of the clusters
      and use kernel-based density estimation of the clusters in every time interval as
      a prior for Bayesian classification of the data in the subsequent time interval.
      COMPARISON WITH EXISTING METHODS: The proposed method was tested and compared to
      Gaussian model-based approach for cluster tracking by using both simulated and
      experimental datasets. RESULTS: The results showed that the proposed non
      parametric kernel-based density estimation of the clusters outperformed the
      sequential Gaussian model fitting in both simulated and experimental data tests.
      CONCLUSIONS: Using non-parametric kernel density-based clustering that makes no
      assumptions on the distribution of the clusters enhances the ability of tracking
      cluster non-stationarity over time with respect to the Gaussian cluster modeling
      approach.

PMID- 24333471
TI  - Evaluation of the effectiveness of Gaussian filtering in distinguishing punctate
      synaptic signals from background noise during image analysis.
AB  - BACKGROUND: Images in biomedical imaging research are often affected by non
      specific background noise. This poses a serious problem when the noise overlaps
      with specific signals to be quantified, e.g. for their number and intensity. A
      simple and effective means of removing background noise is to prepare a filtered
      image that closely reflects background noise and to subtract it from the original
      unfiltered image. This approach is in common use, but its effectiveness in
      identifying and quantifying synaptic puncta has not been characterized in detail.
      NEW ANALYSIS: We report on our assessment of the effectiveness of isolating
      punctate signals from diffusely distributed background noise using one variant of
      this approach, "Difference of Gaussian(s) (DoG)" which is based on a Gaussian
      filter. RESULTS: We evaluated immunocytochemically stained, cultured mouse
      hippocampal neurons as an example, and provided the rationale for choosing
      specific parameter values for individual steps in detecting glutamatergic nerve
      terminals. The intensity and width of the detected puncta were proportional to
      those obtained by manual fitting of two-dimensional Gaussian functions to the
      local information in the original image. COMPARISON WITH EXISTING METHODS: DoG
      was compared with the rolling-ball method, using biological data and numerical
      simulations. Both methods removed background noise, but differed slightly with
      respect to their efficiency in discriminating neighboring peaks, as well as their
      susceptibility to high-frequency noise and variability in object size.
      CONCLUSIONS: DoG will be useful in detecting punctate signals, once its
      characteristics are examined quantitatively by experimenters.

PMID- 24333472
TI  - De novo biosynthesis of linoleic acid and its conversion to the hydrocarbon (Z,Z)
      6,9-heptadecadiene in the astigmatid mite, Carpoglyphus lactis: incorporation
      experiments with 13C-labeled glucose.
AB  - De novo biosynthesis of linoleic acid (LA) and its conversion to (Z,Z)-6,9
      heptadecadiene were examined in Carpoglyphus lactis (Acarina, Carpoglyphidae).
      Experiments involving (13)C-administration using [1-(13)C]-d-glucose revealed
      that (13)C atoms were incorporated into LA of total lipid extracted from the
      mite, resulting in labeling of all even-numbered carbons. This result
      demonstrated that LA was produced from (13)C-labeled acetyl-CoA, which is
      indicative of direct de novo biosynthesis. In these feeding experiments involving
      [1-(13)C]-D-glucose, (13)C atoms were also incorporated into (Z,Z)-6,9
      heptadecadiene, which is one of the major secretory components in the mite. The
      labeling pattern of (Z,Z)-6,9-heptadecadiene at odd-numbered carbons agreed well
      with that of LA after loss of the carboxyl carbon. It was concluded that the
      mites could stably convert LA into (Z,Z)-6,9-heptadecadiene without the dietary
      requirement of this essential fatty acid.

PMID- 24333473
TI  - Molecular and functional characterization of multiple aquaporin water channel
      proteins from the western tarnished plant bug, Lygus hesperus.
AB  - Aquaporins (AQPs) are integral membrane channel proteins that facilitate the
      bidirectional transfer of water or other small solutes across biological
      membranes involved in numerous essential physiological processes. In arthropods,
      AQPs belong to several subfamilies, which contribute to osmoregulation,
      respiration, cryoprotection, anhydrobiosis, and excretion. We cloned and
      characterized five novel AQPs from the western tarnished plant bug, Lygus
      hesperus, a polyphagous insect pest of food and fiber crops throughout western
      North America. The L. hesperus AQPs (LhAQP1-5) belong to different phylogenetic
      subfamilies, have unique transcription profiles and cellular localizations, and
      all transport water (but not glycerol) when heterologously expressed in Xenopus
      laevis oocytes. Our results demonstrate that multiple AQPs with possible
      compensatory functions are produced in L. hesperus that likely play important
      roles in maintaining water homeostasis in this important insect pest. 

PMID- 24333474
TI  - Exogenous administration of coenzyme Q10 restores mitochondrial oxygen
      consumption in the aged mouse brain.
AB  - The level of coenzyme Q (CoQ) has been shown to decrease in an age-dependent
      manner in several types of animals. However, whether CoQ-dependent mitochondrial
      function decreases with aging remains unclear. In this study, we found that
      mitochondrial complexes I and II exhibited significantly reduced oxygen
      consumption in the brains of aged male mice relative to young male mice, although
      this decrease in oxygen consumption was not accompanied by a change in the CoQ9
      or CoQ10 content. Nevertheless, the administration of exogenous CoQ10
      significantly increased the content of CoQ10 and CoQ9 in the brain mitochondria
      of aged male mice and restored complex I- and II-mediated oxygen consumption to
      levels comparable to those observed in young mice. These results indicate that
      mitochondrial oxygen consumption in the brain decreases in aged male mice.
      Furthermore, these results suggest that exogenous CoQ10 restores mitochondrial
      oxygen use to levels equivalent to those observed in young mice. 

PMID- 24333475
TI  - Role of neurosteroids in experimental 3-nitropropionic acid induced neurotoxicity
      in rats.
AB  - Huntington's disease is an autosomal dominant, progressive, and fatal
      neurodegenerative disease characterized by motor and non-motor symptoms. Systemic
      administration of 3-nitropropionic acid, a complex II inhibitor of the electron
      transport chain induces selective striatal lesions in rodents. Neurosteroids are
      synthesized in central nervous system, able to modulate GABAA receptor function
      and has been reported to have neuroprotective action. The present study has been
      designed to investigate the role of neurosteroids such as progesterone and
      pregnenolone which are positive and negative modulators of GABA respectively
      against 3-nitropropionic acid induced experimental Huntington's disease. Systemic
      administration of 3-nitropropionic acid (10mg/kg i.p.) for 14 days significantly
      reduced body weight, locomotor activity, motor coordination, balance beam walk
      performance, antioxidant defense enzymes (reduced glutathione and catalase) and
      significantly increase oxidative stress markers (lipid peroxidation and nitrite
      level) in striatum and cortex. 3-Nitropropionic acid treatment also increases pro
      inflammatory cytokines (TNF-alpha and IL-1beta) level in striatum. Progesterone
      (10, 20mg/kg/day i.p.) treatments for 14 days significantly reversed the
      behavioral, antioxidant defense enzymes, oxidative stress marker and pro
      inflammatory cytokines as compared to the 3-Nitropropionic acid treated group.
      Pregnenolone (1 and 2mg/kg i.p.), a negative modulator of GABAA pretreatment
      significantly reversed the protective effect of progesterone on behavioral and
      biochemical parameters. The results of the present study suggest that the
      positive GABAergic modulation may be beneficial for the treatment of motor
      disorder. 

PMID- 24333476
TI  - Rosuvastatin attenuates atherosclerosis in rats via activation of scavenger
      receptor class B type I.
AB  - In order to investigate the effect and mechanism of action of rosuvastatin on
      atherosclerotic lesion in a Wistar rat model, 16 Wistar rats were fed a
      cholesterol-rich, vitamin D3 overload diet and underwent balloon injury of the
      aorta. One day prior to injury, half of the rats began rosuvastatin treatment
      (5mg/kg/d) via oral gavage. Eight control rats received a basal diet and sham
      operation. After 14 weeks of treatment, the animals were sacrificed. Blood was
      collected to measure lipid and angiotensin II (Ang II) levels and morphologic
      analysis was performed on the aorta. Scavenger receptor-class B type I (SR-BI),
      Ang II type-1 (AT1) receptor and phosphorylated extracellular signal regulated
      kinase 1/2 (p-ERK1/2) protein and mRNA levels were measured via Western blot and
      real time reverse transcriptase polymerase chain reaction, respectively.
      Spearman's rank correlation was utilized to examine the relationships between SR
      BI and Ang II or AT1 receptor expression. The atherosclerosis model group
      demonstrated an increase in plasma lipid levels and aortic plaque formation.
      After 14 weeks of treatment with rosuvastatin, there was a significant decrease
      in plasma lipid and Ang II levels accompanied by an improvement in aortic
      lesions. Rosuvastatin increased the expression of SR-BI but significantly
      inhibited the expression of AT1 receptor and p-ERK1/2. SR-BI protein expression
      was inversely correlated with both the level of Ang II and expression of the AT1
      receptor. In conclusion, rosuvastatin attenuates atherosclerosis in the Wistar
      rat model, and its anti-atherosclerotic activity may be through upregulation of
      SR-BI expression and inhibition of p-ERK1/2 levels and AT1 receptor expression. 

PMID- 24333477
TI  - Tranexamic acid induces kaolin intake stimulating a pathway involving tachykinin
      neurokinin 1 receptors in rats.
AB  - Tranexamic acid suppresses post-partum haemorrhage and idiopathic menorrhagia
      through its anti-fibrinolytic action. Although it is clinically useful, it is
      associated with high risks of side effects such as emesis. Understanding the
      mechanisms underlying tranexamic acid-induced emesis is very important to explore
      appropriate anti-emetic drugs for the prevention and/or suppression of emesis. In
      this study, we examined the receptors involved in tranexamic acid-induced kaolin
      intake in rats, which reflects the drug's clinical emetogenic potential in
      humans. Further, we examined the brain regions activated by administration of
      tranexamic acid and elucidated pivotal pathways of tranexamic acid-induced kaolin
      intake. We examined the effects of ondansetron, a 5-hydroxytryptamine 3 receptor
      antagonist, domperidone, a dopamine 2 receptor antagonist, and aprepitant, a
      tachykinin neurokinin 1 (NK1) receptor antagonist, on tranexamic acid-induced
      kaolin intake in rats. Then, we determined the brain regions that showed
      increased numbers of c-Fos immunoreactive cells. Finally, we examined the effects
      of an antagonist(s) that reduced tranexamic acid-induced kaolin intake on the
      increase in c-Fos immunoreactive cells. Aprepitant significantly decreased
      tranexamic acid-induced kaolin intake. However, neither ondansetron nor
      domperidone decreased kaolin intake. Tranexamic acid significantly increased c
      Fos immunoreactive cells by approximately 5.5-fold and 22-fold in the area
      postrema and nucleus of solitary tract, respectively. Aprepitant decreased the
      number of c-Fos immunoreactive cells in both areas. Tranexamic acid induced
      kaolin intake possibly via stimulation of tachykinin NK1 receptors in rats. The
      tachykinin NK1 receptor could be targeted to prevent and/or suppress emesis in
      patients receiving tranexamic acid. 

PMID- 24333478
TI  - Pharmacokinetic mechanism of enhancement by Radix Pueraria flavonoids on the
      hyperglycemic effects of Cortex Mori extract in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus, characterized by abnormal
      blood glucose evaluation, is a serious chronic disease. In the treatment of the
      disease, alpha-glycosidase inhibitors play an important role for controlling the
      postprandial blood glucose level. Cortex Mori, a traditional Chinese herbal
      medicine, has a long history of use for the treatment of headaches, cough, edema
      and diabetes. Modern pharmacological studies have shown that the herb has
      beneficial effects on the suppression of postprandial blood glucose levels by
      inhibiting alpha-glycosidase activity in the small intestine. 1-Deoxynojirimycin
      (DNJ), the main active ingredient of this herb, is recognized as a potent alpha
      glycosidase inhibitor. Our previous studies have shown that the hypoglycemic
      effect of Cortex Mori extract (CME) was significantly improved when giving CME in
      combination with Radix Pueraria flavonoids (RPF). In the present study, the
      pharmacokinetics and intestinal permeability of DNJ were comparatively
      investigated in rats after being given orally or by intestinal perfusion with CME
      alone or in CME-RPF pairs, to explore the mechanism of this synergistic effect.
      MATERIALS AND METHODS: The role of RPF on the plasma and urine concentrations of
      DNJ from CME orally administered was investigated. Four groups of rats received a
      single oral dose of either CME or CME-RPF, at DNJ equivalent doses of 20 and
      40mg/kg, respectively. After dosing, plasma and urine were collected and assayed
      by LC/MS/MS. In addition, another two groups of rats were used for small
      intestinal perfusion with CME or CME-RPF at DNJ concentration of 10uM. RESULTS:
      Compared to the data when dosing with CME alone, the Cmax of DNJ were decreased
      from 5.78 to 2.94ug/ml (p<0.05) and 10.66 to 5.35ug/ml (p<0.01); Tmax were
      delayed from 0.40 to 0.55h and 0.35 to 0.50h (p<0.05); and MRT were significantly
      prolonged from 1.14 to 1.72h (p<0.05) and 0.95 to 1.62h (p<0.01), after dosing
      with CME-RPF at DNJ doses of 20 and 40mg/kg, respectively. In addition, the
      urinary recovery of DNJ over the first 4h after dosing significantly decreased
      from 48.76% to 33.86%. Effective permeability (Peff) of DNJ was decreased from
      7.53*10(-3) to 3.09*10(-3)cm/s (p<0.05) when RPF was added to CME, when it was
      evaluated using the rat intestinal perfusion model. CONCLUSIONS: All the above
      results demonstrate that RPF was able to suspend and delay the absorption of DNJ,
      but did not affect the total amount of DNJ in the body. The resulting higher
      concentration of DNJ in the small intestine produced a relatively stronger effect
      of depressing the elevation of the postprandial blood glucose level. These
      findings support the important role of RPF in the application of CME on blood
      glucose control.

PMID- 24333479
TI  - Feature selection and multi-kernel learning for sparse representation on a
      manifold.
AB  - Sparse representation has been widely studied as a part-based data representation
      method and applied in many scientific and engineering fields, such as
      bioinformatics and medical imaging. It seeks to represent a data sample as a
      sparse linear combination of some basic items in a dictionary. Gao et al. (2013)
      recently proposed Laplacian sparse coding by regularizing the sparse codes with
      an affinity graph. However, due to the noisy features and nonlinear distribution
      of the data samples, the affinity graph constructed directly from the original
      feature space is not necessarily a reliable reflection of the intrinsic manifold
      of the data samples. To overcome this problem, we integrate feature selection and
      multiple kernel learning into the sparse coding on the manifold. To this end,
      unified objectives are defined for feature selection, multiple kernel learning,
      sparse coding, and graph regularization. By optimizing the objective functions
      iteratively, we develop novel data representation algorithms with feature
      selection and multiple kernel learning respectively. Experimental results on two
      challenging tasks, N-linked glycosylation prediction and mammogram retrieval,
      demonstrate that the proposed algorithms outperform the traditional sparse coding
      methods. 

PMID- 24333480
TI  - Neural network for solving convex quadratic bilevel programming problems.
AB  - In this paper, using the idea of successive approximation, we propose a neural
      network to solve convex quadratic bilevel programming problems (CQBPPs), which is
      modeled by a nonautonomous differential inclusion. Different from the existing
      neural network for CQBPP, the model has the least number of state variables and
      simple structure. Based on the theory of nonsmooth analysis, differential
      inclusions and Lyapunov-like method, the limit equilibrium points sequence of the
      proposed neural networks can approximately converge to an optimal solution of
      CQBPP under certain conditions. Finally, simulation results on two numerical
      examples and the portfolio selection problem show the effectiveness and
      performance of the proposed neural network. 

PMID- 24333481
TI  - Inferring characteristic phenotypes via class association rule mining in the bone
      dysplasia domain.
AB  - Finding, capturing and describing characteristic features represents a key aspect
      in disorder definition, diagnosis and management. This process is particularly
      challenging in the case of rare disorders, due to the sparse nature of data and
      expertise. From a computational perspective, finding characteristic features is
      associated with some additional major challenges, such as formulating a
      computationally tractable definition, devising appropriate inference algorithms
      or defining sound validation mechanisms. In this paper we aim to deal with each
      of these problems in the context provided by the skeletal dysplasia domain. We
      propose a clear definition for characteristic phenotypes, we experiment with a
      novel, class association rule mining algorithm and we discuss our lessons learned
      from both an automatic and human-based validation of our approach. 

PMID- 24333482
TI  - Privacy-preserving record linkage on large real world datasets.
AB  - Record linkage typically involves the use of dedicated linkage units who are
      supplied with personally identifying information to determine individuals from
      within and across datasets. The personally identifying information supplied to
      linkage units is separated from clinical information prior to release by data
      custodians. While this substantially reduces the risk of disclosure of sensitive
      information, some residual risks still exist and remain a concern for some
      custodians. In this paper we trial a method of record linkage which reduces
      privacy risk still further on large real world administrative data. The method
      uses encrypted personal identifying information (bloom filters) in a probability
      based linkage framework. The privacy preserving linkage method was tested on ten
      years of New South Wales (NSW) and Western Australian (WA) hospital admissions
      data, comprising in total over 26 million records. No difference in linkage
      quality was found when the results were compared to traditional probabilistic
      methods using full unencrypted personal identifiers. This presents as a possible
      means of reducing privacy risks related to record linkage in population level
      research studies. It is hoped that through adaptations of this method or similar
      privacy preserving methods, risks related to information disclosure can be
      reduced so that the benefits of linked research taking place can be fully
      realised. 

PMID- 24333483
TI  - Structural characterization of the glycoprotein GP2 core domain from the CAS
      virus, a novel arenavirus-like species.
AB  - Fusion of the viral and host cell membranes is a necessary first step for
      infection by enveloped viruses and is mediated by the envelope glycoprotein. The
      transmembrane subunits from the structurally defined "class I" glycoproteins
      adopt an alpha-helical "trimer-of-hairpins" conformation during the fusion
      pathway. Here, we present our studies on the envelope glycoprotein transmembrane
      subunit, GP2, of the CAS virus (CASV). CASV was recently identified from
      annulated tree boas (Corallus annulatus) with inclusion body disease and is
      implicated in the disease etiology. We have generated and characterized two
      protein constructs consisting of the predicted CASV GP2 core domain. The crystal
      structure of the CASV GP2 post-fusion conformation indicates a trimeric alpha
      helical bundle that is highly similar to those of Ebola virus and Marburg virus
      GP2 despite CASV genome homology to arenaviruses. Denaturation studies
      demonstrate that the stability of CASV GP2 is pH dependent with higher stability
      at lower pH; we propose that this behavior is due to a network of interactions
      among acidic residues that would destabilize the alpha-helical bundle under
      conditions where the side chains are deprotonated. The pH-dependent stability of
      the post-fusion structure has been observed in Ebola virus and Marburg virus GP2,
      as well as other viruses that enter via the endosome. Infection experiments with
      CASV and the related Golden Gate virus support a mechanism of entry that requires
      endosomal acidification. Our results suggest that, despite being primarily
      arenavirus like, the transmembrane subunit of CASV is extremely similar to the
      filoviruses.

PMID- 24333485
TI  - Structural and functional analysis of fucose-processing enzymes from
      Streptococcus pneumoniae.
AB  - Fucose metabolism pathways are present in many bacterial species and typically
      contain the central fucose-processing enzymes fucose isomerase (FcsI), fuculose
      kinase (FcsK), and fuculose-1-phosphate aldolase (FcsA). Fucose initially
      undergoes isomerization by FcsI producing fuculose, which is then phosphorylated
      by FcsK. FcsA cleaves the fuculose-1-phosphate product into lactaldehyde and
      dihydroxyacetone phosphate, which can be incorporated into central metabolism
      allowing the bacterium to use fucose as an energy source. Streptococcus
      pneumoniae has fucose-processing operons containing homologs of FcsI, FcsK, and
      FcsA; however, this bacterium appears unable to utilize fucose as an energy
      source. To investigate this contradiction, we performed biochemical and
      structural studies of the S. pneumoniae fucose-processing enzymes SpFcsI, SpFcsK,
      and SpFcsA. These enzymes are demonstrated to act in a sequential manner to
      ultimately produce dihydroxyacetone phosphate and have structural features
      entirely consistent with their observed biochemical activities. Analogous to the
      regulation of the Escherichia coli fucose utilization operon, fuculose-1
      phosphate appears to act as an inducing molecule for activation of the S.
      pneumoniae fucose operon. Despite our evidence that S. pneumoniae appears to have
      the appropriate regulatory and biochemical machinery for fucose metabolism, we
      confirmed the inability of the S. pneumoniae TIGR4 strain to grow on fucose or on
      the H-disaccharide, which is the probable substrate of the transporter for the
      pathway. On the basis of these observations, we postulate that the S. pneumoniae
      fucose-processing pathway has a non-metabolic role in the interaction of this
      bacterium with its human host.

PMID- 24333484
TI  - TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral
      immunity.
AB  - Tripartite motif (TRIM) proteins have been implicated in multiple cellular
      functions, including antiviral activity. Research efforts so far indicate that
      the antiviral activity of TRIMs relies, for the most part, on their function as
      E3-ubiquitin ligases. A substantial number of the TRIM family members have been
      demonstrated to mediate innate immune cell signal transduction and subsequent
      cytokine induction. In addition, a subset of TRIMs has been shown to restrict
      viral replication by directly targeting viral proteins. Although the body of work
      on the cellular roles of TRIM E3-ubiquitin ligases has rapidly grown over the
      last years, many aspects of their molecular workings and multi-functionality
      remain unclear. The antiviral function of many TRIMs seems to be conferred by
      specific isoforms, by sub-cellular localization and in cell-type-specific
      contexts. Here we review recent findings on TRIM antiviral functions, current
      limitations and an outlook for future research. 

PMID- 24333486
TI  - Steric mechanism of auto-inhibitory regulation of specific and non-specific DNA
      binding by the ETS transcriptional repressor ETV6.
AB  - DNA binding by the ETS transcriptional repressor ETV6 (or TEL) is auto-inhibited
      ~50-fold due to an alpha-helix that sterically blocks its ETS domain binding
      interface. Using NMR spectroscopy, we demonstrate that this marginally stable
      helix is unfolded, and not displaced to a non-inhibitory position, when ETV6 is
      bound to DNA containing a consensus (5')GGAA(3') recognition site. Although
      significantly lower in affinity, binding to non-specific DNA is auto-inhibited ~5
      fold and is also accompanied by helix unfolding. Based on NMR chemical shift
      perturbations, both specific and non-specific DNA are bound via the same
      canonical ETS domain interface. However, spectral perturbations are smaller for
      the non-specific complex, suggesting weaker and less well-defined interactions
      than in the specific complex. In parallel, the crystal structure of ETV6 bound to
      a specific DNA duplex was determined. The structure of this complex reveals that
      a non-conserved histidine residue in the ETS domain recognition helix helps
      establish the specificity of ETV6 for DNA-binding sites containing
      (5')GGAA(3')versus(5')GGAT(3'). These studies provide a unified steric mechanism
      for attenuating ETV6 binding to both specific and non-specific DNA and expand the
      repertoire of characterized auto-inhibitory strategies utilized to regulate ETS
      factors. 

PMID- 24333488
TI  - Peritoneal dialysis and inflammation.
AB  - Peritoneal dialysis (PD) is a kidney replacement therapy for end stage renal
      disease (ESRD) patients. Despite being a lifesaving treatment, the rate of
      mortality in patients under PD is elevated, mainly due to the chronic peritoneal
      dysfunction which is characterized by inflammation, peritoneal fibrosis and
      neoangiogenesis. The inflammatory process is trigged and modulated by the type of
      the peritoneal dialysis solutions (PDSs) used during PD. Currently, different
      PDSs are commercially available: (i) the conventional solutions; (ii) solutions
      of neutral pH containing low concentration of glucose degradation products
      (GDPs); (iii) solutions with icodextrin; and (iv) solutions containing taurine.
      Therefore, the aim of this review is to describe the different types of
      peritoneal dialysis solutions used during PD and their relationship with systemic
      and intraperitoneal inflammation. Some studies suggested that solutions of
      neutral pH containing low concentration of GDPs, icodextrin and taurine have
      better biocompatibility and lower influence on the inflammatory process compared
      to the conventional one. On the other hand, the studies, in general, were
      performed with a small population and for a short period of time. Therefore,
      further well-designed and -controlled clinical trials with larger number of
      individuals are required in order to better understand the role of different
      peritoneal dialysis solution types in the development of inflammation in patients
      with chronic peritoneal dialysis. Accordingly, studies that are more well
      designed, well-controlled and with a larger number of patients are needed to
      explain and define the role of different types of PDS in the inflammation
      development in patients with chronic peritoneal dialysis. 

PMID- 24333487
TI  - Molecular insights into the recognition of N-terminal histone modifications by
      the BRPF1 bromodomain.
AB  - The monocytic leukemic zinc finger (MOZ) histone acetyltransferase (HAT)
      acetylates free histones H3, H4, H2A, and H2B in vitro and is associated with up
      regulation of gene transcription. The MOZ HAT functions as a quaternary complex
      with the bromodomain-PHD finger protein 1 (BRPF1), inhibitor of growth 5 (ING5),
      and hEaf6 subunits. BRPF1 links the MOZ catalytic subunit to the ING5 and hEaf6
      subunits, thereby promoting MOZ HAT activity. Human BRPF1 contains multiple
      effector domains with known roles in gene transcription, as well as chromatin
      binding and remodeling. However, the biological function of the BRPF1 bromodomain
      remains unknown. Our findings reveal novel interactions of the BRPF1 bromodomain
      with multiple acetyllysine residues on the N-terminus of histones and show that
      it preferentially selects for H2AK5ac, H4K12ac, and H3K14ac. We used chemical
      shift perturbation data from NMR titration experiments to map the BRPF1
      bromodomain ligand binding pocket and identified key residues responsible for
      coordination of the post-translationally modified histones. Extensive molecular
      dynamics simulations were used to generate structural models of bromodomain
      histone ligand complexes, to analyze hydrogen bonding and other interactions, and
      to calculate the binding free energies. Our results outline the molecular
      mechanism driving binding specificity of the BRPF1 bromodomain for discrete
      acetyllysine residues on the N-terminal histone tails. Together, these data
      provide insights into how histone recognition by the bromodomain directs the
      biological function of BRPF1, ultimately targeting the MOZ HAT complex to
      chromatin substrates. 

PMID- 24333489
TI  - The calculated risk of defibrillator implantation.

PMID- 24333490
TI  - The effect of intermittent atrial tachyarrhythmia on heart failure or death in
      cardiac resynchronization therapy with defibrillator versus implantable
      cardioverter-defibrillator patients: a MADIT-CRT substudy (Multicenter Automatic
      Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).
AB  - OBJECTIVES: This study aimed to investigate the effect of both history of
      intermittent atrial tachyarrhythmias (IAT) and in-trial IAT on the risk of heart
      failure (HF) or death comparing cardiac resynchronization therapy with
      defibrillator (CRT-D) to implantable cardioverter-defibrillator (ICD) treatment
      in mildly symptomatic HF patients with left bundle branch block (LBBB).
      BACKGROUND: Limited data exist regarding the benefit of CRT-D in patients with
      IAT. METHODS: The benefit of CRT-D in reducing the risk of HF/death was evaluated
      using multivariate Cox models incorporating the presence of, respectively, a
      history of IAT at baseline and time-dependent development of in-trial IAT during
      follow-up in 1,264 patients with LBBB enrolled in the MADIT-CRT (Multicenter
      Automatic Defibrillator Implantation Trial With Cardiac Resynchronization
      Therapy) study. RESULTS: The overall beneficial effect of CRT-D versus ICD on the
      risk of HF/death was not significantly different between LBBB patients with or
      without history of IAT (HR: 0.50, p = 0.028, and HR: 0.46, p < 0.001,
      respectively; p for interaction = 0.79). Among patients who had in-trial IAT, CRT
      D was associated with a significant 57% reduction in the risk of HF/death
      compared with ICD-only therapy (HR: 0.43, p = 0.047), similar to the effect of
      the device among patients who did not have IAT (HR: 0.47, p < 0.001; p for
      interaction = 0.85). The percentage of patients with biventricular pacing >=92%
      was similar in both groups (p = 0.43). Consistent results were shown for the
      benefit of CRT-D among patients who had in-trial atrial fibrillation/flutter (HR:
      0.30, p = 0.027; p for interaction = 0.41). CONCLUSIONS: In the MADIT-CRT study,
      the clinical benefit of CRT-D in LBBB patients was not attenuated by prior
      history of IAT or by the development of in-trial atrial tachyarrhythmias. (MADIT
      CRT: Multicenter Automatic Defibrillator Implantation Trial With Cardiac
      Resynchronization Therapy; NCT00180271).

PMID- 24333491
TI  - Developing a risk model for in-hospital adverse events following implantable
      cardioverter-defibrillator implantation: a report from the NCDR (National
      Cardiovascular Data Registry).
AB  - OBJECTIVES: To better inform patients and physicians of the expected risk of
      adverse events and to assist hospitals' efforts to improve the outcomes of
      patients undergoing implantable cardioverter-defibrillator (ICD) implantation, we
      developed and validated a risk model using data from the NCDR (National
      Cardiovascular Data Registry) ICD Registry. BACKGROUND: ICD prolong life in
      selected patients, but ICD implantation carries the risk of periprocedural
      complications. METHODS: We analyzed data from 240,632 ICD implantation procedures
      between April 1, 2010, and December 31, 2011 in the registry. The study group was
      divided into a derivation (70%) and a validation (30%) cohort. Multivariable
      logistic regression was used to identify factors associated with in-hospital
      adverse events (complications or mortality). A parsimonious risk score was
      developed on the basis of beta estimates derived from the logistic model.
      Hierarchical models were then used to calculate risk-standardized complication
      rates to account for differences in case mix and procedural volume. RESULTS:
      Overall, 4,388 patients (1.8%) experienced at least 1 in-hospital complication or
      death. Thirteen factors were independently associated with an increased risk of
      adverse outcomes. Model performance was similar in the derivation and validation
      cohorts (C-statistics = 0.724 and 0.719, respectively). The risk score
      characterized patients into low- and-high risk subgroups for adverse events (<=10
      points, 0.3%; >=30 points, 4.2%). The risk-standardized complication rates varied
      significantly across hospitals (median: 1.77, interquartile range 1.54, 2.14,
      5th/95th percentiles: 1.16/3.15). CONCLUSIONS: We developed a simple model that
      predicts risk for in-hospital adverse events among patients undergoing ICD
      placement. This can be used for shared decision making and to benchmark hospital
      performance.

PMID- 24333492
TI  - Impact of academic year timing on percutaneous coronary intervention outcomes at
      training institutions.

PMID- 24333493
TI  - Pharmacodynamic evaluation of switching from ticagrelor to prasugrel in patients
      with stable coronary artery disease: Results of the SWAP-2 Study (Switching Anti
      Platelet-2).
AB  - OBJECTIVES: The goal of this study was to evaluate the pharmacodynamic effects of
      switching patients from ticagrelor to prasugrel. BACKGROUND: Clinicians may need
      to switch between more potent P2Y12 inhibitors because of adverse effects or
      switch to the use of a once-daily dosing regimen due to compliance issues.
      METHODS: After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose
      (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin
      treated patients (N = 110) with stable coronary artery disease were randomized to
      continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a
      60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction
      unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated
      phosphoprotein phosphorylation assay) at baseline (before and after the run-in
      phase) and 2, 4, 24, and 48 h and 7 days after randomization. RESULTS: Platelet
      reactivity was significantly greater at 24 and 48 h after switching to prasugrel
      versus continued therapy with ticagrelor, although to a lesser extent in those
      receiving an LD. Mean PRU remained significantly higher in the combined prasugrel
      groups versus the ticagrelor group (least-squares mean difference: 46 [95%
      confidence interval 25 to 67]) and did not meet the primary noninferiority
      endpoint (upper limit of the confidence interval <=45), although PRU in the
      prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of
      high on-treatment platelet reactivity were higher at 24 and 48 h in both
      prasugrel groups. At 7 days, there was no difference in high on-treatment
      platelet reactivity rate between the combined prasugrel and ticagrelor groups.
      CONCLUSIONS: Compared with continued ticagrelor therapy, switching from
      ticagrelor to prasugrel therapy was associated with an increase in platelet
      reactivity that was partially mitigated by the administration of an LD.

PMID- 24333494
TI  - Cardiac resynchronization therapy in patients with intermittent atrial
      arrhythmias: will cardiac resynchronization therapy be good for all?

PMID- 24333495
TI  - Late bleeding and neurological sequelae after HeartMate II left ventricular
      assist device: risk factors from the prequel.

PMID- 24333496
TI  - Intestinal cholesterol absorption and cardiovascular risk.

PMID- 24333497
TI  - Reply: Intestinal cholesterol absorption and cardiovascular risk.

PMID- 24333498
TI  - The Long and Short of It: Insights Into the Short QT Syndrome.

PMID- 24333499
TI  - Rectal carbamazepine as effective long-acting treatment after cluster seizures
      and status epilepticus.
AB  - Carbamazepine (CBZ) is the gold standard antiepileptic drug (AED) for focal onset
      seizures. Despite CBZ being the benchmark AED, with readily available therapeutic
      drug monitoring, patients presenting with recurrent secondarily generalized tonic
      clonic (or cluster) seizures or generalized tonic-clonic status epilepticus (SE)
      are primarily treated with other long-acting agents. The aim of the study was to
      examine the potential use of rectal (PR) CBZ as alternative long-acting treatment
      to parenteral AEDs following the termination of cluster seizures or SE with acute
      intravenous therapies. Oral CBZ syrup was given PR using 400-mg equivalent
      aliquots. Serum CBZ levels were requested after administration to confirm
      achievement of minimum therapeutic levels (total CBZ>20MUmol.L(-1)). Where levels
      were subtherapeutic, the procedure was repeated using 400-mg CBZ bolus aliquots
      until therapeutic levels were achieved. Seven patients received PR CBZ to manage
      cluster seizures or SE following the initial termination of acute seizures with
      IV therapies including benzodiazepines. Six patients had no prior history of
      seizures, and 1 patient with a prior history was not taking AED therapy at the
      time of presentation. All patients subsequently remained seizure-free, and
      therapeutic CBZ levels were achieved in 6 of the 7 subjects within 5-10h of
      initial CBZ dosing. In conclusion, the present study reports 7 patients who were
      safely and effectively treated with PR CBZ, which proved to be a viable and safe
      alternative to parenteral AEDs for maintenance of seizure freedom. 

PMID- 24333500
TI  - The child behavior checklist and youth self-report in adolescents with epilepsy:
      testing measurement invariance of the attention and thought problems subscales.
AB  - The objective of this study was to test for the measurement invariance of the
      Attention and Thought Problems subscales of the Child Behavior Checklist (CBCL)
      and Youth Self-Report (YSR) in a population-based sample of adolescents with and
      without epilepsy. Data were obtained from the 14-year follow-up of the Mater
      University Study of Pregnancy in which 33 adolescents with epilepsy and 1068
      healthy controls were included for analysis. Confirmatory factor analysis was
      used to test for measurement invariance between adolescents with and without
      epilepsy. Structural equation modeling was used to test for group differences in
      attention and thought problems as measured with the CBCL and YSR. Measurement
      invariance was demonstrated for the original CBCL Attention Problems and YSR
      Thought Problems. After the removal of ambiguous items ("confused" and
      "daydreams"), measurement invariance was established for the YSR Attention
      Problems. The original and reduced CBCL Thought Problems were noninvariant.
      Adolescents with epilepsy had significantly more symptoms of behavioral problems
      on the CBCL Attention Problems, beta=0.51, p=0.002, compared with healthy
      controls. In contrast, no significant differences were found for the YSR
      Attention and Thought Problems, beta=-0.11, p=0.417 and beta=-0.20, p=0.116,
      respectively. In this population-based sample of adolescents with epilepsy, the
      CBCL Attention Problems and YSR Thought Problems appear to be valid measures of
      behavioral problems, whereas the YSR Attention Problems was valid only after the
      removal of ambiguous items. Replication of these findings in clinical samples of
      adolescents with epilepsy that overcome the limitations of the current study is
      warranted. 

PMID- 24333501
TI  - Systemic therapy in advanced uterine adenosarcoma with sarcomatous overgrowth.

PMID- 24333502
TI  - Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway.
AB  - Aberrations in various cellular signaling pathways are instrumental in regulating
      cellular metabolism, tumor development, growth, proliferation, metastasis and
      cytoskeletal reorganization. The fundamental cellular signaling cascade involved
      in these processes, the phosphatidylinositol 3-kinase/protein kinase-B/mammalian
      target of rapamycin (PI3K/AKT/mTOR), closely related to the mitogen-activated
      protein kinase (MAPK) pathway, is a crucial and intensively explored
      intracellular signaling pathway in tumorigenesis. Various activating mutations in
      oncogenes together with the inactivation of tumor suppressor genes are found in
      diverse malignancies across almost all members of the pathway. Substantial
      progress in uncovering PI3K/AKT/mTOR alterations and their roles in tumorigenesis
      has enabled the development of novel targeted molecules with potential for
      developing efficacious anticancer treatment. Two approved anticancer drugs,
      everolimus and temsirolimus, exemplify targeted inhibition of PI3K/AKT/mTOR in
      the clinic and many others are in preclinical development as well as being tested
      in early clinical trials for many different types of cancer. This review focuses
      on targeted PI3K/AKT/mTOR signaling from the perspective of novel molecular
      targets for cancer therapy found in key pathway members and their corresponding
      experimental therapeutic agents. Various aberrant prognostic and predictive
      biomarkers are also discussed and examples are given. Novel approaches to
      PI3K/AKT/mTOR pathway inhibition together with a better understanding of
      prognostic and predictive markers have the potential to significantly improve the
      future care of cancer patients in the current era of personalized cancer
      medicine. 

PMID- 24333503
TI  - The role of FAK in tumor metabolism and therapy.
AB  - Focal adhesion kinase (FAK) plays a vital role in tumor cell proliferation,
      survival and migration. Altered metabolic pathways fuel rapid tumor growth by
      accelerating glucose, lipid and glutamine processing. Besides the mitogenic
      effects of FAK, evidence is accumulating supporting the association between hyper
      activated FAK and aberrant metabolism in tumorigenesis. FAK can promote glucose
      consumption, lipogenesis, and glutamine dependency to promote cancer cell
      proliferation, motility, and survival. Clinical studies demonstrate that FAK
      related alterations of tumor metabolism are associated with increased risk of
      developing solid tumors. Since FAK contributes to the malignant phenotype, small
      molecule inhibition of FAK-stimulated bioenergetic and biosynthetic processes can
      provide a novel approach for therapeutic intervention in tumor growth and
      invasion. 

PMID- 24333504
TI  - Novel experimental model of non-infectious pharyngitis in rats.
AB  - INTRODUCTION: Currently, there is a paucity of scientific literature and reports
      related to screening models for non-infectious type of pharyngitis. In this
      context, we made a sincere attempt to establish a novel animal model for
      screening drugs against non-infectious pharyngitis in rats. We have considered
      the use of pyridine, croton oil and their combination for inducing non-infectious
      pharyngitis in rats. METHODS: Various concentrations of pyridine were applied
      topically to the pharyngeal region of rats and the extent of inflammation was
      assessed by Evans Blue (EB) dye exudation test, evaluating the serum levels of
      proinflammatory cytokines and histopathology. Dexamethasone and diclofenac were
      used as reference standards. RESULTS: Upon pyridine application (2.5%, 5%, 10%,
      20%, 40% and 80% in saline), dose-dependent increase in EB dye extravasation was
      observed (increased vascular permeability). In addition, the levels of TNF-alpha
      (P<0.01) and IL-6 (P<0.01) were significantly increased compared to control.
      Furthermore, the histopathology of pharyngeal tissue showed hypertrophy of
      submucosal glands, severe inflammation of the pharynx characterised by presence
      of mononuclear cells, neutrophils along with haemorrhages and congestion;
      however, normal control animals showed normal cytoarchitecture of pharynx.
      Indeed, dexamethasone (0.25, 0.5 and 1 mg/kg, i.v.) and diclofenac (1, 2.5 and 5
      mg/kg, i.v.) showed dose-dependent protection against pyridine-induced
      pharyngitis. Further, the possible mechanism of pyridine-induced pharyngitis is
      thought to be primarily mediated through phospholipase A2 and cyclooxygenase
      (COX) pathway. CONCLUSION: These findings suggest that pyridine-induced
      pharyngitis is a simple and versatile novel animal model for screening the drugs
      against non-infectious pharyngitis in rats.

PMID- 24333505
TI  - Analysis of 27 vascular-related proteins reveals that NT-proBNP is a potential
      biomarker for Alzheimer's disease and mild cognitive impairment: a pilot-study.
AB  - Alzheimer's disease (AD) is a severe neurodegenerative disease. Cerebrovascular
      changes often accompany AD-related pathology. Despite a considerable progress in
      the diagnostic accuracy of AD, no blood biomarkers have been established so far.
      The aim of the present study was to search for changes in plasma levels of 27
      vascular-related proteins of healthy controls, patients with mild cognitive
      impairment (MCI) and AD. In a sample of 80 participants we showed that out of
      these 27 proteins, six proteins were slightly changed (up to 1.5*) in AD (alpha2
      macroglobulin, apolipoprotein-A1, plasminogen activator inhibitor, RAGE, Tissue
      Inhibitors of Metalloproteinases-1 and Trombospondin-2) and one marker (serum
      amyloid A) was enhanced up to 6* but with a very high variance. However, N
      terminal pro-brain natriuretic peptide (NT-proBNP) was significantly enhanced
      both in MCI and AD patients (1.9*). In a second analysis of a sample of 110
      subjects including younger healthy controls, we confirmed that NT-proBNP has the
      potential to be a stable candidate protein for both diagnosis and AD disease
      progression. 

PMID- 24333507
TI  - DNMT3B inhibits the re-expression of genes associated with induced pluripotency.
AB  - DNMT3B is a de novo DNA methyltransferase that is highly expressed in mouse and
      human embryonic stem (ES) cells and has been shown to be essential for
      differentiation of mouse ES cells toward different lineages. In the present
      study, we found that DNMT3B is rapidly down-regulated in human ES cells during
      retinoic acid (RA)-induced differentiation compared with DNMT3A2, which is also
      highly expressed in ES cells. Silencing of DNMT3B in human ES cells by an
      inducible shRNAi system leads to a reduction of clonal ability of the stem cells,
      while expression of OCT4 and NANOG is unchanged. By contrast, the germline
      specific genes VASA and SCP3 and the surface antigen BE12 are down regulated
      following DNMT3B knockdown. Upon retinoic acid-induced differentiation, we found
      that depletion of DNMT3B leads to a decrease in expression of the surface antigen
      A2B5 and of neural tube-associated genes PAX7 and BRN3A. Consistent with its
      importance in stem cell differentiation, we observed that silencing of DNMT3B
      facilitates the generation of cells that bear the hallmarks of pluripotency. Our
      findings suggest a role of DNMT3B in controlling the differentiation of human ES
      cells and in the generation of iPS cells.

PMID- 24333508
TI  - Calmodulin orchestrates the heteromeric assembly and the trafficking of KCNQ2/3
      (Kv7.2/3) channels in neurons.
AB  - Mutations in KCNQ2 and KCNQ3 genes are responsible for benign familial neonatal
      seizures and epileptic encephalopathies. Some of these mutations have been shown
      to alter the binding of calmodulin (CaM) to specific C-terminal motifs of KCNQ
      subunits, known as the A and B helices. Here, we show that the mutation I342A in
      the A helix of KCNQ3 abolishes CaM interaction and strongly decreases the
      heteromeric association with KCNQ2. The assembly of KCNQ2 with KCNQ3 is essential
      for their expression at the axon initial segment (AIS). We find that the I342A
      mutation alters the targeting of KCNQ2/3 subunits at the AIS. However, the
      traffic of the mutant channels was rescued by provision of exogenous CaM. We show
      that CaM enhances the heteromeric association of KCNQ2/KCNQ3-I342A subunits by
      binding to their B helices in a calcium-dependent manner. To further assert the
      implication of CaM in channel assembly, we inserted a mutation in the second coil
      coil domain of KCNQ2 (KCNQ2-L638P) to prevent its heteromerization with KCNQ3. We
      observe that the expression of a Ca(2+)-insensitive form of CaM favours the
      assembly of KCNQ3 with KCNQ2-L638P. Our data thus indicate that both apoCaM and
      Ca(2+)/CaM bind to the C-terminal domains of KCNQ2 and KCNQ3 subunits, and
      regulate their heteromeric assembly. Hence, CaM may control the composition and
      distribution of KCNQ channels in neurons. 

PMID- 24333506
TI  - The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma
      cell motility.
AB  - Malignant astrocytomas are highly invasive into adjacent and distant regions of
      the normal brain. Rho GTPases are small monomeric G proteins that play important
      roles in cytoskeleton rearrangement, cell motility, and tumor invasion. In the
      present study, we show that the knock down of StarD13, a GTPase activating
      protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through
      modulating focal adhesion dynamics and cell adhesion. This effect is mediated by
      the resulting constitutive activation of RhoA and the subsequent indirect
      inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based
      Forster Resonance Energy Transfer (FRET), we show that RhoA activity localizes
      with focal adhesions at the basal surface of astrocytoma cells. Moreover, the
      knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of
      cells, which makes them defective in retracting their tail. This study highlights
      the importance of the regulation of RhoA activity in focal adhesions of
      astrocytoma cells and establishes StarD13 as a GAP playing a major role in this
      process. 

PMID- 24333509
TI  - Nitrifying moving bed biofilm reactor (MBBR) biofilm and biomass response to long
      term exposure to 1  degrees C.
AB  - This study aims to investigate moving bed biofilm reactor (MBBR) nitrification
      rates, nitrifying biofilm morphology, biomass viability as well as bacterial
      community shifts during long-term exposure to 1  degrees C. Long-term exposure to
      1  degrees C is the key operational condition for potential ammonia removal
      upgrade units to numerous northern region treatment systems. The average
      laboratory MBBR ammonia removal rate after long-term exposure to 1  degrees C was
      measured to be 18 +/- 5.1% as compared to the average removal rate at 20  degrees
      C. Biofilm morphology and specifically the thickness along with biomass viability
      at various depths in the biofilm were investigated using variable pressure
      electron scanning microscope (VPSEM) imaging and confocal laser scanning
      microscope (CLSM) imaging in combination with viability live/dead staining. The
      biofilm thickness along with the number of viable cells showed significant
      increases after long-term exposure to 1  degrees C. Hence, this study observed
      nitrifying bacteria with higher activities at warm temperatures and a slightly
      greater quantity of nitrifying bacteria with lower activities at cold
      temperatures in nitrifying MBBR biofilms. Using DNA sequencing analysis,
      Nitrosomonas and Nitrosospira (ammonia oxidizers) as well as Nitrospira (nitrite
      oxidizer) were identified and no population shift was observed between 20 
      degrees C and after long-term exposure to 1  degrees C. 

PMID- 24333510
TI  - Reply: To PMID 23376320.

PMID- 24333511
TI  - Reply: To PMID 23978500.

PMID- 24333512
TI  - Endoscopic detection of proximal serrated lesions and pathologic identification
      of sessile serrated adenomas/polyps vary on the basis of center.
AB  - BACKGROUND & AIMS: We investigated rates of detection of proximal serrated
      lesions in a cohort of average-risk patients undergoing screening colonoscopies.
      METHODS: We reviewed results from screening colonoscopies performed by attending
      gastroenterologists at 32 endoscopy centers from 2008-2010. Pathology slides were
      interpreted at the individual centers. For this analysis, serrated lesions
      included hyperplastic polyps larger than 10 mm, those interpreted as sessile
      serrated adenomas (or sessile serrated polyp), and traditional serrated adenomas.
      Rates of detection for conventional adenomas and serrated lesions were compared
      among centers. RESULTS: A total of 5778 lesions were detected in 7215 screening
      colonoscopies. Of the 5548 lesions with pathology results, 3008 (54.2%) were
      conventional adenomas, 350 (6.3%) were serrated, and 232 (4.2%) were proximal
      serrated. The proportion of colonoscopies with at least 1 proximal serrated
      lesion was 2.8% (range among centers, 0%-9.8%). The number of serrated lesions
      per colonoscopy ranged from 0.00-0.11 (average, 0.05 +/- 0.25). Overall lesion
      detection rates correlated with proximal serrated lesion detection rates (R =
      0.91, P < .0001); conventional adenoma and proximal serrated lesion detection
      rates also correlated (R = .43, P = .025). The detection rate of proximal
      serrated lesions differed significantly among centers (P < .0001); odds ratios
      for detection ranged from 0-0.79. Some centers' pathologists never identified
      proximal serrated lesions as sessile serrated adenomas/polyps. CONCLUSIONS: In an
      average-risk screening cohort, detection of proximal serrated lesions varied
      greatly among endoscopy centers. There was also substantial variation among
      pathologists in identification of sessile serrated adenomas/polyps. Nationally, a
      significant proportion of proximal serrated lesions may be missed during
      colonoscopy examination or incorrectly identified during pathology assessment.
      ClinicalTrials.gov Number: NCT00855348.

PMID- 24333513
TI  - Outcomes after urethroplasty for radiotherapy induced bulbomembranous urethral
      stricture disease.
AB  - PURPOSE: We recently demonstrated that radiotherapy induced urethral strictures
      can be successfully managed with urethroplasty. We increased size and followup in
      our multi-institutional cohort, and evaluated excision and primary anastomosis as
      treatment for radiotherapy induced urethral strictures. MATERIALS AND METHODS: A
      retrospective review was performed of 72 patients from 3 academic institutions
      treated for radiotherapy induced bulbomembranous strictures. Outcome parameters
      of successful repair included recurrence, incontinence and erectile dysfunction.
      RESULTS: Among the 72 men treated for radiotherapy induced strictures 66 (91.7%)
      underwent excision and primary anastomosis. Mean followup was 3.5 years (median
      3.1, range 0.8 to 11.2). Prostate cancer was the most common reason for
      radiotherapy (in 64 of 66, 96.9%). External beam radiotherapy and brachytherapy
      were performed in 28 of 66 men (42.4%) each, and a combination of both was
      performed in 9 (13.6%). Mean time from radiation to excision and primary
      anastomosis was 6.4 years (range 1 to 20) and mean stricture length was 2.3 cm
      (range 1 to 6). Successful reconstruction was achieved in 46 men (69.7%). Mean
      time to recurrence was 10.2 months (range 1 to 64) with new onset of incontinence
      observed in 12 men (18.5%). This was associated with stricture length greater
      than 2 cm (p = 0.013) and treatment center (p <0.001). The rate of erectile
      dysfunction remained stable (preoperative 45.6%, postoperative 50.9%, p = 0.71).
      Radiotherapy type did not affect stricture length (p = 0.41), recurrence risk (p
      = 0.91), postoperative incontinence (p = 0.88) or erectile dysfunction (p =
      0.53). CONCLUSIONS: Radiotherapy induced bulbomembranous urethral strictures can
      be successfully managed with excision and primary anastomosis. Substitution
      urethroplasty with graft or flap is needed infrequently. Patients should be
      counseled on the potential risks of urinary incontinence and erectile
      dysfunction.

PMID- 24333514
TI  - Satisfaction with information used to choose prostate cancer treatment.
AB  - PURPOSE: After being diagnosed with prostate cancer men must assimilate
      information regarding the cancer. Satisfaction with information reflects the
      evaluation of information sources used before treatment to select a therapy. We
      describe the use and helpfulness of several information sources available to
      prostate cancer survivors. We also identified factors associated with
      satisfaction with information. MATERIALS AND METHODS: A total of 1,204 men with
      newly diagnosed prostate cancer were enrolled in the prospective, multicenter
      Prostate Cancer Outcomes and Satisfaction with Therapy Quality Assessment study.
      The validated satisfaction with information domain of the Service Satisfaction
      Scale-Cancer was administered to subjects 2 months after treatment. The
      relationship between several factors, such as demographics, socioeconomic
      factors, cancer severity and types of information sources, and satisfaction with
      information were evaluated using multiple regression. RESULTS: Sources of
      information endorsed by subjects varied by race, education and study site. The
      most helpful sources were treatment description by the treating physician
      (33.1%), Internet sites (18.9%) and books (18.1%). In multiple variable models
      patient age (p = 0.005) and information provided by the physician regarding
      outcomes in their patients (p = 0.01) were independently associated with patient
      satisfaction with the information provided. CONCLUSIONS: Various information
      sources were used and endorsed as helpful by subjects, although results for
      physician patients was the only source independently associated with satisfaction
      with information. Providing patients with information about possible or expected
      courses of care and outcomes may improve satisfaction.

PMID- 24333515
TI  - Improving detection of clinically significant prostate cancer: magnetic resonance
      imaging/transrectal ultrasound fusion guided prostate biopsy.
AB  - PURPOSE: Given the limitations of prostate specific antigen and standard biopsies
      for detecting prostate cancer, we evaluated the cancer detection rate and
      external validity of a magnetic resonance imaging/transrectal ultrasound fusion
      guided prostate biopsy system used at the National Institutes of Health.
      MATERIALS AND METHODS: We performed a phase III trial of a magnetic resonance
      imaging/transrectal ultrasound fusion guided prostate biopsy system with
      participants enrolled between 2012 and 2013. A total of 153 men consented to the
      study and underwent 3 Tesla multiparametric magnetic resonance imaging with an
      endorectal coil for clinical suspicion of prostate cancer. Lesions were
      classified as low or moderate/high risk for prostate cancer. Magnetic resonance
      imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate
      biopsy were performed and 105 men were eligible for analysis. RESULTS: Mean
      patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The
      overall cancer detection rate was 62.9% (66 of 105 patients). The cancer
      detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65)
      vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p<0.05).
      Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core
      biopsy, respectively (p<0.05). Magnetic resonance imaging/transrectal ultrasound
      fusion guided biopsy detected prostate cancer that was missed by standard 12-core
      biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically
      significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically
      insignificant on 12-core biopsy to clinically significant prostate cancer
      necessitating treatment. CONCLUSIONS: Magnetic resonance imaging/transrectal
      ultrasound fusion guided biopsy can improve prostate cancer detection. The
      results of this trial support the external validity of this platform and may be
      the next step in the evolution of prostate cancer management.

PMID- 24333516
TI  - Tumor target volume for focal therapy of prostate cancer-does multiparametric
      magnetic resonance imaging allow for a reliable estimation?
AB  - PURPOSE: We determined whether endorectal multiparametric magnetic resonance
      imaging at 1.5 Tesla could predict tumor target volume in the perspective of
      focal therapy of prostate cancer. MATERIALS AND METHODS: A total of 84
      consecutive patients underwent multiparametric magnetic resonance imaging before
      radical prostatectomy. The volume of each suspicious area detected on magnetic
      resonance imaging and of all surgical histological foci was determined by
      planimetry. We first used each magnetic resonance imaging sequence (T2-weighted,
      diffusion weighted and dynamic contrast enhanced) and then the sequence showing
      the largest tumor area (multiparametric volume). Finally, the largest area of any
      sequence was used to calculate a target volume according to the volume of a
      cylinder. Agreement between magnetic resonance imaging and pathological findings
      was assessed by linear regression and residual analysis. RESULTS: Histology
      revealed 99 significant tumors with a volume of greater than 0.2 cc and/or a
      Gleason score of greater than 6. Of the tumors 16 (16.2%) were undetected by
      multiparametric magnetic resonance imaging. Linear regression analysis showed
      that tumor volume estimated by T2-weighted or diffusion weighted imaging
      correlated significantly with pathological volume (r(2) = 0.82 and 0.83,
      respectively). Residuals from diffusion weighted imaging volume estimations did
      not significantly differ from 0. Nevertheless, diffusion weighted imaging
      underestimated pathological volume in 43 of 87 cases (49%) by a mean of 0.56 cc
      (range 0.005 to 2.84). Multiparametric and target volumes significantly
      overestimated pathological volume by a mean of 16% and 44% with underestimation
      in 28 (32%) and 15 cases (17%), respectively. Volume underestimation was
      significantly higher for tumor foci less than 0.5 cc. The percent of Gleason
      grade 4 did not influence tumor volume estimation. CONCLUSIONS: Magnetic
      resonance imaging can detect most significant tumors. However, delineating a
      target volume may require further adjustment before planning magnetic resonance
      imaging targeted focal treatment.

PMID- 24333517
TI  - Loss of col8a1a function during zebrafish embryogenesis results in congenital
      vertebral malformations.
AB  - Congenital vertebral malformations (CVM) occur in 1 in 1000 live births and in
      many cases can cause spinal deformities, such as scoliosis, and result in
      disability and distress of affected individuals. Many severe forms of the
      disease, such as spondylocostal dystostosis, are recessive monogenic traits
      affecting somitogenesis, however the etiologies of the majority of CVM cases
      remain undetermined. Here we demonstrate that morphological defects of the
      notochord in zebrafish can generate congenital-type spine defects. We
      characterize three recessive zebrafish leviathan/col8a1a mutant alleles ((m531,
      vu41, vu105)) that disrupt collagen type VIII alpha1a (col8a1a), and cause
      folding of the embryonic notochord and consequently adult vertebral column
      malformations. Furthermore, we provide evidence that a transient loss of col8a1a
      function or inhibition of Lysyl oxidases with drugs during embryogenesis was
      sufficient to generate vertebral fusions and scoliosis in the adult spine. Using
      periodic imaging of individual zebrafish, we correlate focal notochord defects of
      the embryo with vertebral malformations (VM) in the adult. Finally, we show that
      bends and kinks in the notochord can lead to aberrant apposition of osteoblasts
      normally confined to well-segmented areas of the developing vertebral bodies. Our
      results afford a novel mechanism for the formation of VM, independent of defects
      of somitogenesis, resulting from aberrant bone deposition at regions of misshapen
      notochord tissue. 

PMID- 24333518
TI  - Fusion of HPV L1 into Shigella surface IcsA: a new approach in developing live
      attenuated Shigella-HPV vaccine.
AB  - Despite the success of L1 virus-like particles (VLPs) vaccines in prevention of
      high-risk human papillomavirus (HPV) infection and cervical cancer, extraordinary
      high cost for the complete vaccination has impeded widespread use of the vaccine
      in resource-poor countries, where cervical cancers impose greater challenge.
      Presentation of HPV L1 protein by attenuated pathogenic bacteria through natural
      infection provides a promising low-cost and convenient alternative. Here, we
      describe the construction and characterization of attenuated L1-expressing
      Shigella vaccine candidate, by fusion of L1 into the autotransporter of Shigella
      sonnei, IcsA, an essential virulence factor responsible for actin-based motility.
      The functional alpha domain of IcsA was replaced by codon-optimized L1 gene with
      independent open reading frames (ORFs) facilitated by suicide vector pJCB12. The
      L1 gene was stabilized in the genome of recombinant S. sonnei with protein
      expression and assembly of VLPs in the bacterial cytoplasm. Through conjunctival
      route vaccination in guinea pigs, L1-containing S. sonnei was able to elicit
      specific immune response to HPV16 L1 VLP as well as bacterial antigens. The
      results demonstrated the feasibility of the novel stratagem to develop
      prophylactic Shigella-HPV vaccines. 

PMID- 24333520
TI  - Influence of seasonal variation on water quality in tropical water distribution
      system: is the disease burden significant?
AB  - Recent evidence shows that water distribution system (WDS) is a major risk factor
      in piped water supply system and the degree of contamination of water in WDS is
      usually influenced by seasonal variation. Risk assessment studies eliminate the
      effect of seasonality whenever annualized estimate of concentration of
      contaminants in water is used to determine the risk to health. In tropical
      climate where strong seasonal variation prevails, the excess risk during dry and
      hot season, above the annualized risk can be significant. This study investigates
      what impact seasonal adjustment may have on health improvement targets for WDS.
      Water quality data of two Nigerian water supply schemes were used to estimate the
      impact of WDS on water quality. Seasonal deviation from the annualized impact was
      quantified as the latent risk in disability-adjusted life years (DALYs). The
      hazards identified in both WDSs were cadmium and lead, and the estimated 95th
      percentile risk of the metals, over the course of dry season was about 31-38%,
      and 1-3% higher than the estimated yearly average risk, respectively. Wilcoxon
      signed-rank test showed that the risk distributions during the dry season was
      significantly higher (p < 0.05) than the yearly average. The median latent risks
      (5th, 95th-percentiles), for both WDS were 0.014 (7.6 * 10(-3), 0.023) and 4.8 *
      10(-3) (-, 7.6 * 10(-3)) DALYs/person/year for cadmium and 0.87 * 10(-3) (0, 0.1
      * 10(-3)) and 0.16 * 10(-3) (0, 0.031 * 10(-3)) DALYs/person/year, respectively,
      for lead. These risks are substantially higher than the WHO limit (1 * 10(-6)
      DALYs/person/year). Therefore, to achieve effective health improvement target,
      mitigation measures should be planned and executed by season. 

PMID- 24333519
TI  - Bio-active engineered 50 nm silica nanoparticles with bone anabolic activity:
      therapeutic index, effective concentration, and cytotoxicity profile in vitro.
AB  - Silica-based nanomaterials are generally considered to be excellent candidates
      for therapeutic applications particularly related to skeletal metabolism however
      the current data surrounding the safety of silica based nanomaterials is
      conflicting. This may be due to differences in size, shape, incorporation of
      composite materials, surface properties, as well as the presence of contaminants
      following synthesis. In this study we performed extensive in vitro safety
      profiling of ~ 50 nm spherical silica nanoparticles with OH-terminated or
      Polyethylene Glycol decorated surface, with and without a magnetic core, and
      synthesized by the Stober method. Nineteen different cell lines representing all
      major organ types were used to investigate an in vitro lethal concentration (LC)
      and results revealed little toxicity in any cell type analyzed. To calculate an
      in vitro therapeutic index we quantified the effective concentration at 50%
      response (EC50) for nanoparticle-stimulated mineral deposition activity using
      primary bone marrow stromal cells (BMSCs). The EC50 for BMSCs was not
      substantially altered by surface or magnetic core. The calculated Inhibitory
      concentration 50% (IC50) for pre-osteoclasts was similar to the osteoblastic
      cells. These results demonstrate the pharmacological potential of certain silica
      based nanomaterial formulations for use in treating bone diseases based on a
      favorable in vitro therapeutic index.

PMID- 24333521
TI  - Coupling Fenton and biological oxidation for the removal of nitrochlorinated
      herbicides from water.
AB  - The combination of Fenton and biological oxidation for the removal of the
      nitrochlorinated herbicides alachlor, atrazine and diuron in aqueous solution has
      been studied. The H2O2 dose was varied from 20 to 100% of the stoichiometric
      amount related to the initial chemical oxygen demand (COD). The effluents from
      Fenton oxidation were analyzed for ecotoxicity, biodegradability, total organic
      carbon (TOC), COD and intermediate byproducts. The chemical step resulted in a
      significant improvement of the biodegradability in spite of its negligible or
      even slightly negative effect on the ecotoxicity. Working at 60% of the
      stoichiometric H2O2 dose allowed obtaining highly biodegradable effluents in the
      cases of alachlor and atrazine. That dose was even lower (40% of the
      stoichiometric) for diuron. The subsequent biological treatment was carried out
      in a sequencing batch reactor (SBR) and the combined Fenton-biological treatment
      allowed up to around 80% of COD reduction. 

PMID- 24333522
TI  - Cylindrospermopsis raciborskii dominates under very low and high nitrogen-to
      phosphorus ratios.
AB  - In freshwater ecosystems, a variety of factors mediate phytoplankton community
      structure, including herbivore community structure, light availability,
      temperature, mixing, and absolute and relative nutrient concentrations (total
      nitrogen (TN), total phosphorus (TP)). Ecological stoichiometry examines how the
      nutrient content of organisms and their environment may mediate population-,
      community-, and ecosystem-level processes. The manipulation of N:P ratios is a
      widely regarded tool for managing phytoplankton species composition given that
      nitrogen-fixing cyanobacteria should dominate algal communities under relatively
      low N:P (<64:1, by atoms) given their ability to convert dissolved dinitrogen gas
      into organic nitrogen. However, due to the physiological expense of nitrogen
      fixation, diazotrophs should be outcompeted by non-nitrogen fixing phytoplankton
      under higher N:P when other environmental factors are similar. We tested this
      hypothesis in a field experiment using 2500-L limnocorrals installed in a
      eutrophic lake (ambient N:P ~40:1 (by atoms); TN ~1360 MUgL(-1); TP ~75 MUgL(
      1)). At the start of the experiment, we randomly assigned limnocorrals among the
      ambient (40:1) and low (7:1) or high (122:1) N:P treatments (n = 4
      replicates/treatment), which were established by adding P or N at the start of
      the experiment, respectively. The phytoplankton community in the enclosures at
      the start of the experiment was diverse (i.e., 18 phytoplankton genera) and
      dominated by chlorophytes (including Coelastrum and Scenedesmus (30% and 13% of
      total biomass, respectively)) and cyanobacteria (including Anabaena and
      Cylindrospermopsis (23% and 17% of total biomass, respectively)). In contrast to
      predictions based on ecological stoichiometry, the phytoplankton community in all
      N:P treatments increased in abundance and was almost entirely composed of the
      nitrogen-fixing cyanobacterium, Cylindrospermopsis raciborskii, by the conclusion
      of the study. Moreover, concentrations of the cyanobacterial neurotoxin,
      saxitoxin, were enhanced under the two highest N:P conditions. The ability of C.
      raciborskii to dominate phytoplankton communities under such extreme N:P shows
      that short-term management of nutrient stoichiometry through fertilization is not
      likely to be effective for controlling blooms of this noxious cyanobacterium and
      may help to explain the rapid expansion of this invasive species to temperate
      latitudes. 

PMID- 24333523
TI  - Transaortic stent grafting of a Kommerell diverticulum arising from a right-sided
      aortic arch.
AB  - In this article, we report the case of a 68-year-old woman who presented with
      shortness of breath. Respiratory function tests showed a slightly obstructive
      physiology. Computed tomography (CT) results revealed an aberrant left subclavian
      artery and a Kommerell diverticulum arising from a right-sided aortic arch that
      was compressing the trachea and the surrounding tissues. A median sternotomy was
      performed with the patient under circulatory arrest with moderate hypothermia,
      and a transaortic stent graft was inserted to exclude the Kommerell diverticulum.
      The aberrant left subclavian artery was ligated and an axillo-axillar bypass was
      constructed. Postoperative CT showed complete exclusion of the Kommerell
      diverticulum without an endoleak. The patient's breathing difficulty was
      resolved, and she was discharged uneventfully. This procedure should be
      considered as an alternative strategy for exclusion of Kommerell diverticulum. 

PMID- 24333524
TI  - Stent graft placement for a tracheoinnominate artery fistula.
AB  - A 68-year-old woman with ventilator-dependent respiratory failure and multiple
      comorbidities developed acute massive hemoptysis. Computed tomographic angiogram
      revealed a 3.9-cm pseudoaneurysm arising from the innominate artery abutting the
      trachea. The patient was successfully treated with stent graft insertion via the
      right common carotid artery, with exclusion of the aneurysm from the proximal
      innominate to the right common carotid artery, with ligation of the proximal
      right subclavian artery and right common carotid to subclavian artery bypass. The
      patient remained medically stable for 3 months after the procedure with no
      evidence of endoleak or infection. She then developed recurrent hemoptysis with
      fatal cardiac arrest. Open surgical repair has been the treatment of choice for
      tracheoinnominate artery fistula. However, direct repair confers a high mortality
      risk. Endovascular exclusion offers a less invasive treatment option for
      tracheoinnominate artery fistula and can serve as a bridge for patients with
      potential for becoming better surgical candidates. 

PMID- 24333525
TI  - An unusual case of familial lymphedema.
AB  - A 47-year-old man with stable stage II chronic kidney disease and episodic
      diarrhea presented with chronic, progressive bilateral lower extremity
      lymphedema. His mother and 2 brothers had similar acral swelling. Thus, a
      diagnosis of typical primary familial lymphedema was suspected. Approximately 1
      year later, progressive azotemia and proteinuria ensued. A renal biopsy suggested
      Fabry disease, which was confirmed by enzymatic and genetic testing. In addition,
      Fabry disease was diagnosed in his mother and 2 male siblings with lower
      extremity lymphedema. As this case illustrates, Fabry disease is an
      underappreciated and often unrecognized cause of familial lymphedema. 

PMID- 24333526
TI  - Evaluation of spinal cord ischemia with a retrievable stent graft is useful for
      determining the type of repair for a case of patch aneurysm.
AB  - Patch aneurysms after thoracoabdominal aortic aneurysm repair are a serious late
      complication. We treated a patient with patch aneurysm (originating at the artery
      of Adamkiewicz) involving a portion of an implanted graft from a previous
      operation. First, thoracic endovascular aneurysm repair was planned. A
      retrievable stent graft was inserted, and motor-evoked potentials were monitored
      to evaluate spinal cord ischemia. Significant changes in the motor-evoked
      potentials were observed, and permanent stent graft placement was abandoned.
      Later, open surgery was performed. The patient showed no postoperative paraplegia
      and was discharged in good condition. 

PMID- 24333527
TI  - Quality of life before hyperhidrosis treatment as a predictive factor for
      oxybutynin treatment outcomes in palmar and axillary hyperhidrosis.
AB  - BACKGROUND: Studies have suggested that quality of life (QOL) evaluation before
      video-assisted thoracoscopic sympathectomy for patients with hyperhidrosis may
      serve as a predictive factor for positive postoperative outcomes. Our study aims
      to analyze if this tendency is also observed in patients treated with oxybutynin
      for palmar and axillary hyperhidrosis. METHODS: Five hundred sixty-five patients
      who submitted to a protocol treatment with oxybutynin were retrospectively
      analyzed between January 2007 and January 2012 and were divided into 2 groups
      according to QOL assessment before treatment. The groups consisted of 176
      patients with "poor" and 389 patients with "very poor" QOL evaluation before
      oxybutynin treatment. Outcomes involving improvements in QOL and clinical
      progression of hyperhidrosis were evaluated using a validated clinical
      questionnaire that was specifically designed to assess satisfaction in patients
      with excessive sweating. RESULTS: Improvements in hyperhidrosis after oxybutynin
      were observed in 65.5% of patients with very poor pretreatment QOL scores and in
      75% of patients with poor pretreatment QOL scores, and the only adverse event
      associated with oxybutynin treatment was dry mouth, which was observed with
      greater intensity in patients with very poor initial QOL evaluation. CONCLUSION:
      Improvements in hyperhidrosis after oxybutynin treatment were similar in both
      groups, suggesting that QOL before treatment is not a predictive factor for
      clinical outcomes, contrasting with surgical results that disclose significantly
      better results in patients with initially poorer QOL analysis.

PMID- 24333528
TI  - Endovascular strategy for the elective treatment of concomitant aortoiliac
      aneurysm and symptomatic large bowel diverticular disease.
AB  - BACKGROUND: The purpose of this study was to evaluate the strategy for treatment
      of patients presenting with asymptomatic diverticular disease of the large bowel
      associated with an asymptomatic aortoiliac aneurysmal (AAA) disease. METHODS:
      Sixty-nine patients were included in this retrospective study. The patients were
      divided into 5 groups according to the type and sequence of the surgical
      treatment: 32 patients (47%) underwent colectomy followed by a staged open AAA
      repair (group A); 10 patients (14%) were treated with open AAA repair followed by
      a staged colectomy (group B); 13 patients (18%) received endovascular aneurysm
      repair (EVAR) followed by a staged bowel resection (group C); 8 patients (12%)
      had a bowel resection followed by staged EVAR (group D); and 6 patients (9%)
      underwent simultaneous open AAA repair and bowel resection (group E). Primary end
      points were mortality and complications after any of the procedures. Secondary
      end point was the time interval between the staged procedures. RESULTS: The
      cumulative death rate for delayed treatment of AAA was 6.5% and 0% for delayed
      treatment of diverticular disease [P=0.22]. The mean time interval between the
      staged procedures was 11 days for EVAR/colon resection (group C and group D) and
      73 days for open AAA repair/colon resection (group A and group B; P<0.01).
      CONCLUSIONS: EVAR allows a significant reduction in the time required between AAA
      repair and colon resection, but no definite rule can be established regarding the
      sequence of staged procedures. Combined procedures should be reserved for
      selected cases.

PMID- 24333529
TI  - Mycotic inferior mesenteric artery aneurysm secondary to native valve
      endocarditis caused by coagulase-negative Staphylococcus.
AB  - Inferior mesenteric artery (IMA) aneurysms are the rarest of all visceral artery
      aneurysms, with most resulting from atherosclerotic disease. Mycotic IMA
      aneurysms are exceptionally uncommon and only 2 cases have been reported in the
      literature. Coagulase-negative staphylococcus (CNS) is often considered a
      contaminant; however, increasing reports of certain strains causing endocarditis
      are becoming more prevalent. We report a case of a mycotic IMA aneurysm, in the
      setting of native valve endocarditis caused by Staphylococcus simulans, a strain
      of CNS. To our knowledge, this is the third report of a mycotic IMA aneurysm, and
      the first account of this usually benign pathogen leading to aneurysmal
      degeneration in this location. 

PMID- 24333530
TI  - The study of associative learning: mapping from psychological to neural levels of
      analysis.
AB  - One of the major achievements of the last century of research in experimental
      psychology is the identification of a coherent set of theories and principles to
      characterize the nature of simple forms of associative learning. Major advances
      are also currently being made at a rapid pace in the neurobiology of associative
      learning, and, interestingly, we are beginning to see how a mapping from a
      psychological level of analysis to underlying neurobiological mechanisms is
      possible. This collection of papers honors the illustrative careers of four major
      learning theorists from the experimental psychology tradition (Robert Rescorla,
      Allan Wagner, Nicholas Mackintosh, Anthony Dickinson) who have helped shape our
      understanding of behavioral principles. The collection of works in this special
      issue reflects common interests among researchers working at both psychological
      and neurobiological levels of analysis towards a more comprehensive understanding
      of basic associative learning processes as they relate to several key issues
      identified and intensively studied by these influential learning theorists. These
      consist of the questions regarding (1) the critical conditions enabling learning,
      (2) the contents of learning, and (3) the rules that translate learning into
      performance. In one way or another, the separate contributions in this issue
      address these fundamental questions as they relate to a wide variety of currently
      exciting topics in the study of the neurobiology of learning and memory. 

PMID- 24333531
TI  - Do inhibitory immune receptors play a role in the etiology of autoimmune disease?
AB  - Inhibitory receptors are thought to be important in balancing immune responses.
      The general assumption is that lack of inhibition predisposes for autoimmune
      diseases. As reviewed here, various experimental and clinical data support this
      assumption. However, in humans genetic evidence implicates only a limited number
      of inhibitory receptors. GWAS have established common variation in a few
      inhibitory receptor genes, such as FCgammaRIIB, PD-1 and CTLA-4 as risk factors.
      The question arises whether inhibitory receptor function is a major determinant
      of autoimmune disease. In this respect, the finding that genetic variation in CSK
      and PTPN22 is strongly associated with multiple autoimmune diseases is of
      interest. We propose a model in which the molecules encoded by these genes are
      downstream of inhibitory receptors. We conclude that common genetic variation of
      inhibitory receptors, with few exceptions, is not a determining factor for
      autoimmunity in humans. However, common downstream signaling pathways are. 

PMID- 24333532
TI  - Severe eczema and Hyper-IgE in Loeys-Dietz-syndrome - contribution to new
      findings of immune dysregulation in connective tissue disorders.
AB  - Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by monoallelic
      mutations in TGFBR1 and TGFBR2, which encode for subunits of the transforming
      growth factor beta (TGFbeta) receptor. Affected patients are identified by
      vascular aneurysms with tortuosity and distinct morphological presentations
      similar to Marfan syndrome; however, an additional predisposition towards asthma
      and allergy has recently been found. We describe two patients with a novel
      missense mutation in TGFBR1 presenting with highly elevated levels of IgE and
      severe eczema similar to autosomal-dominant Hyper-IgE syndrome (HIES). Mild
      allergic manifestations with normal up to moderately increased IgE were observed
      in 3 out of 6 additional LDS patients. A comparison of this cohort with 4 HIES
      patients illustrates the significant overlap of both syndromes including eczema
      and elevated IgE as well as skeletal and connective tissue manifestations. 

PMID- 24333533
TI  - Use of gene-modified regulatory T-cells to control autoimmune and alloimmune
      pathology: is now the right time?
AB  - Adoptive immunotherapy using genetically targeted T-cells has recently begun to
      achieve impressive clinical impact in selected tumor types. Furthermore, long
      term follow-up studies indicate thus far that integrating viral vectors do not
      elicit clinically evident genotoxicity in T-cells, unlike hematopoietic stem
      cells. The optimism engendered by this clinical experience provides a platform
      for consideration of the extended use of this technology in other disease types.
      One area of particular interest entails the harnessing of regulatory T-cells
      (Tregs) in order to down-regulate unwanted immune responses. Increasing evidence
      supports the efficacy of this approach in pre-clinical models of autoimmune
      disease and allograft rejection. Nonetheless, questions remain about optimal host
      cell, transgene cargo, phenotypic stability of engineered cells in vivo and
      potential for toxicity. Here, we review the evidence that genetically engineered
      Tregs can effectively dampen pathogenic immune responses and critically evaluate
      the prospects for clinical development of this approach. 

PMID- 24333534
TI  - Folate receptor-targeted aminopterin therapy is highly effective and specific in
      experimental models of autoimmune uveitis and autoimmune encephalomyelitis.
AB  - EC0746 is a rationally designed anti-inflammatory drug conjugate consisting of a
      modified folic acid-based ligand linked to a gamma-hydrazide analog of
      aminopterin. In this report, EC0746's effectiveness was evaluated against
      experimental retinal S-antigen (PDSAg) induced autoimmune uveitis (EAU) and
      myelin-basic-protein induced autoimmune encephalomyelitis (EAE). In both models,
      functional FR-beta was detected on activated macrophages in local (retinal or
      central-nervous-system, respectively) and systemic (peritoneal cavity) sites of
      inflammation. In myelin-rich regions of EAE rats, an increased uptake of (99m)Tc
      EC20 (etarfolatide; a FR-specific radioimaging agent) was also observed. EC0746
      treatment at disease onset suppressed the clinical severity of both EAU and EAE,
      and it strongly attenuated progressive histopathological changes in the affected
      organs. In all parameters assessed, EC0746 activity was completely blocked by a
      benign folate competitor, suggesting that these therapeutic outcomes were
      specifically FR-beta mediated. EC0746 may emerge as a useful macrophage
      modulating agent for treating inflammatory episodes of organ-specific
      autoimmunity. 

PMID- 24333535
TI  - Protective role of JAK/STAT signaling against renal fibrosis in mice with
      unilateral ureteral obstruction.
AB  - Inflammation is involved in renal fibrosis, a final common pathway for kidney
      diseases. To clarify how JAK/STAT/SOCS system was involved in renal fibrosis, UUO
      was induced in BALB/c or SOCS3(+/-) mice in the presence or absence of JAK
      inhibitor-incorporated nanoparticle (pyridine6-PGLA). UUO increased pSTAT3 and
      subsequently elevated SOCS3 levels in the obstructed kidneys. pSTAT3 levels were
      further increased in SOCS3(+/-) mice. UUO-induced renal fibrosis was markedly
      suppressed in SOCS3(+/-) mice, while it was aggravated by pre-treatment with
      pyridine6-PGLA. Although there were no differences in renal mRNA levels of TGF
      beta and collagens between wild and SOCS3(+/-) mice, MMP-2 activity was enhanced
      in SOCS3(+/-) UUO mice. Activated MMP-2 was completely suppressed by pyridine6
      PGLA-pre-treatment. TNF-alpha one of JAK/STAT activators, increased pSTAT3 levels
      and subsequently induced MMP-2 activation in proximal tubular cells. These
      results suggest that JAK/STAT3 signaling may play a role in repair process of
      renal fibrosis in UUO partly via MMP-2 activation. 

PMID- 24333536
TI  - Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family
      cytokines.
AB  - Semaphorin 7A (sema7a) plays a major role in TGF-beta1-induced lung fibrosis.
      Based on the accumulating evidence that eosinophils contribute to
      fibrosis/remodeling in the airway, we hypothesized that airway eosinophils may be
      a significant source of sema7a. In vivo, sema7a was expressed on the surface of
      circulating eosinophils and upregulated on bronchoalveolar lavage eosinophils
      obtained after segmental bronchoprovocation with allergen. Based on mRNA levels
      in unfractionated and isolated bronchoalveolar cells, eosinophils are the
      predominant source of sema7a. In vitro, among the members of the IL-5-family
      cytokines, sema7a protein on the surface of blood eosinophils was increased more
      by IL-3 than by GM-CSF or IL-5. Cytokine-induced expression of cell surface
      sema7a required translation of newly synthesized protein. Finally, a recombinant
      sema7a induced alpha-smooth muscle actin production in human bronchial
      fibroblasts. semaphorin 7A is a potentially important modulator of eosinophil
      profibrotic functions in the airway remodeling of patients with chronic asthma. 

PMID- 24333538
TI  - Tainting the soul: purity concerns predict moral judgments of suicide.
AB  - Moral violations are typically defined as actions that harm others. However,
      suicide is considered immoral even though the perpetrator is also the victim. To
      determine whether concerns about purity rather than harm predict moral
      condemnation of suicide, we presented American adults with obituaries describing
      suicide or homicide victims. While harm was the only variable predicting moral
      judgments of homicide, perceived harm (toward others, the self, or God) did not
      significantly account for variance in moral judgments of suicide. Instead,
      regardless of political and religious views and contrary to explicit beliefs
      about their own moral judgments, participants were more likely to morally condemn
      suicide if they (i) believed suicide tainted the victims' souls, (ii) reported
      greater concerns about purity in an independent questionnaire, (iii) experienced
      more disgust in response to the obituaries, or (iv) reported greater trait
      disgust. Thus, suicide is deemed immoral to the extent that it is considered
      impure. 

PMID- 24333537
TI  - Acute ablation of DP thymocytes induces up-regulation of IL-22 and Foxn1 in TECs.
AB  - Thymic epithelial cells (TECs) provide the basic architecture for the development
      of thymocytes. TEC is regenerative after impairment in thymus of young mice.
      However, how this regeneration program is governed remains unclear. Transcription
      factor Foxn1 is a central mediator of the differentiation and function of TEC. We
      examined the relation between thymic injury and Foxn1 in TEC. Total body
      irradiation (TBI) treatments induced up-regulation of Foxn1 in TEC, which was
      abolished when thymic function recovered. Specific depletion of double positive
      (DP) thymocytes triggered the up-regulation of Foxn1. On the other hand,
      extracellular IL-22 is a potential regulator of homeostasis of TEC. We
      demonstrated that TBI treatments also induced the up-regulation of intrathymic IL
      22. Expression pattern of Foxn1 shares similar characteristics with IL-22.
      Furthermore, Foxn1 related genes that regulate the function of TEC were also up
      regulated. Thus, our data reveal that TBI treatment triggers regeneration program
      of TEC. 

PMID- 24333540
TI  - EcoliOverExpressionDB: a database of recombinant protein overexpression in E.
      coli.
AB  - Recombinant protein production is a significant biotechnological process as it
      allows researchers to produce a specific protein in desired quantities.
      Escherichia coli (E. coli) is the most popular heterologous expression host for
      the production of recombinant proteins due to its advantages such as low cost,
      high-productivity, well-characterized genetics, simple growth requirements and
      rapid growth. There are a number of factors that influence the expression level
      of a recombinant protein in E. coli which are the gene to be expressed, the
      expression vector, the expression host, and the culture condition. The major
      motivation to develop our database, EcoliOverExpressionDB, is to provide a means
      for researchers to quickly locate key factors in the overexpression of certain
      proteins. Such information would be a useful guide for the overexpression of
      similar proteins in E. coli. To the best of the present researchers' knowledge,
      in general and specifically in E. coli, EcoliOverExpressionDB is the first
      database of recombinant protein expression experiments which gathers the
      influential parameters on protein overexpression and the results in one place.
      AVAILABILITY: EcoliOverExpressionDB is freely available and accessible using all
      major browsers at http://birg4.fbb.utm.my:8080/EcoliOverExpressionDB/.

PMID- 24333539
TI  - Subliminal action priming modulates the perceived intensity of sensory action
      consequences.
AB  - The sense of control over the consequences of one's actions depends on
      predictions about these consequences. According to an influential computational
      model, consistency between predicted and observed action consequences attenuates
      perceived stimulus intensity, which might provide a marker of agentic control. An
      important assumption of this model is that these predictions are generated within
      the motor system. However, previous studies of sensory attenuation have typically
      confounded motor-specific perceptual modulation with perceptual effects of
      stimulus predictability that are not specific to motor action. As a result, these
      studies cannot unambiguously attribute sensory attenuation to a motor locus. We
      present a psychophysical experiment on auditory attenuation that avoids this
      pitfall. Subliminal masked priming of motor actions with compatible prime-target
      pairs has previously been shown to modulate both reaction times and the explicit
      feeling of control over action consequences. Here, we demonstrate reduced
      perceived loudness of tones caused by compatibly primed actions. Importantly,
      this modulation results from a manipulation of motor processing and is not
      confounded by stimulus predictability. We discuss our results with respect to
      theoretical models of the mechanisms underlying sensory attenuation and
      subliminal motor priming. 

PMID- 24333541
TI  - Effects of bathing solution on tensile properties of the cornea.
AB  - The cornea is a transparent tissue with the major functions of protecting the
      inner contents of the eye and refracting incoming light. The biomechanical
      properties of the cornea strongly depend on the microstructure and composition of
      the stromal layer, a hydrated bio-gel. The uniaxial strip testing is a convenient
      and well-accepted experimental technique for characterizing corneal material
      parameters. It is known that the water content of specimens in this method
      depends on the osmolality of the bathing solution. The present study was designed
      to investigate the effects of different bathing solutions on uniaxial tensile
      material properties of the cornea. The tensile behavior of bovine corneal samples
      was measured in six different bathing solutions, i.e., hypertonic solution (12%
      NaCl solution), common preserving isotonic solutions (e.g., phosphate buffer
      saline, ophthalmic balanced salt solution, and 0.9% NaCl solution), hypotonic
      solution (distilled water), and neutral solution (mineral oil). It was observed
      that the bathing solution had significant influence on the tensile behavior of
      the corneal samples. In particular, the specimens tested in bathing solutions
      causing less swelling had significantly stiffer tensile properties. Furthermore,
      a simple mathematical model based on Voigt composite material model was developed
      to represent the measured solution-dependent tensile properties. The present
      study suggests that extra attention should be paid to corneal thickness
      (hydration) in uniaxial tensile experiments. It also provides important data on
      tensile properties of the cornea; such information could significantly contribute
      to improving the accuracy of numerical predictions of corneal biomechanics.

PMID- 24333542
TI  - Behavioral and neurochemical effects of dietary methyl donor deficiency combined
      with unpredictable chronic mild stress in rats.
AB  - Methyl donor deficiencies and chronic stress cause depression independently, but
      their interaction has never been thoroughly evaluated. In our study, methyl donor
      deficient diet and chronic stress condition consisted respectively of a B2, B9,
      B12, and choline-free diet and a chronic mild stress procedure. Rats were
      randomly assigned to six groups with three "diet" conditions (free-feeding, pair
      fed and methyl donor deficient diet) and two "stress" conditions (no-stress and
      stress) and were evaluated in the open-field, the elevated plus-maze and the
      forced swimming test. After the behavioral evaluation, corticosterone and
      homocysteine plasma levels were measured and dopamine, DOPAC, serotonin, 5HIAA
      concentrations were evaluated in several brain areas. Rats given a methyl donor
      deficient diet for 11 weeks causing elevated plasma homocysteine levels were
      compared to pair-fed and free-feeding rats with or without unpredictable chronic
      mild stress. Regardless of stress environmental conditions, the methyl donor
      deficient diet decreased plasma corticosterone levels and caused disinhibition in
      the elevated plus-maze condition relative to both control groups. However, stress
      potentiated the effects of the deficient regimen on rearing in the open-field and
      climbing in the forced swim test. The dietary changes involved in behavior and
      plasma corticosterone could be caused by homocysteine-induced decreases in
      dopamine and 5-hydroxytryptamine metabolites in selective brain regions and it
      can be noted that regardless of stress-conditions, methyl donor deficient diet
      decreases DOPAC/dopamine and 5HIAA/serotonin ratios in striatum and hypothalamus
      and selectively 5HIAA/serotonin ratio in the sensorimotor cortex. Our
      experimental data is particularly relevant in the context of neuropsychiatric
      disorders frequently associated with folate deficiency and hyperhomocysteinemia. 

PMID- 24333543
TI  - Cardiac implantable electronic device infections: incidence, risk factors, and
      the effect of the AigisRx antibacterial envelope.
AB  - BACKGROUND: Cardiac implantable electronic device (CIED) infection is associated
      with morbidity and mortality. OBJECTIVES: To determine the incidence and risk
      factors for CIED infection, to develop a scoring index for risk stratification,
      and to analyze the effect of the AIGISRx envelope on infection rates. METHODS:
      Consecutive patients who underwent a CIED procedure were identified and surveyed
      for 6 months for the development of an infection necessitating removal of all
      implanted hardware. RESULTS: In the pre-envelope era, an infection occurred in 25
      (1.5%) of 1651 patients. After its availability, an envelope was used in 275
      (22%) of 1240 patients; an infection occurred in 8 (0.6%) patients in this era (P
      = .029 vs pre-envelope). In the overall cohort of 2891 patients, the infection
      rate was 1.2% and 3.5% in patients with an implantable cardioverter-defibrillator
      device and those with a cardiac resynchronization therapy defibrillator device,
      respectively (P = .018); in these patients, 7 independent risk factors predicted
      infection: early pocket re-exploration, male sex, diabetes, upgrade procedure,
      heart failure, hypertension, and glomerular filtration rate < 60 mL/min. A
      composite risk score (0-25; C index 0.72; 95% confidence interval 0.61-0.83) was
      created by weight, adjusting these 7 factors: 3 groups emerged-low risk (score 0
      7; 1% infection), medium risk (score 8-14; 3.4% infection), and high risk (score
      >=15; 11.1% infection). The envelope reduced infections by 79% and 100% in the
      medium- and high-risk groups, respectively. CONCLUSIONS: CIED infection most
      commonly occurred in patients with an implantable cardioverter-defibrillator
      device and those with a cardiac resynchronization therapy defibrillator device. A
      composite score based on clinical variables appeared feasible for infection risk
      stratification. The AIGISRx envelope significantly lowered the risk of CIED
      infection. Randomized clinical data are warranted.

PMID- 24333544
TI  - Characterization of cardiolipins and their oxidation products by LC-MS analysis.
AB  - Cardiolipins, a class of mitochondria-specific lipid molecules, is one of the
      most unusual and ancient phospholipids found in essentially all living species.
      Typical of mammalian cells is the presence of vulnerable to oxidation
      polyunsaturated fatty acid resides in CL molecules. The overall role and
      involvement of cardiolipin oxidation (CLox) products in major intracellular
      signaling as well as extracellular inflammatory and immune responses have been
      established. However, identification of individual peroxidized molecular species
      in the context of their ability to induce specific biological responses has not
      been yet achieved. This is due, at least in part, to technological difficulties
      in detection, identification, structural characterization and quantitation of
      CLox associated with their very low abundance and exquisite diversification. This
      dictates the need for the development of new methodologies for reliable,
      sensitive and selective analysis of both CLox. LC-MS-based oxidative lipidomics
      with high mass accuracy instrumentation as well as new software packages are
      promising in achieving the goals of expedited and reliable analysis of
      cardiolipin oxygenated species in biosamples. 

PMID- 24333546
TI  - Ejaculatio praecox, erectio praecox, and detumescentia praecox as symptoms of a
      hypertonic state in lifelong premature ejaculation: a new hypothesis.
AB  - In the last two decades, in vivo animal research and human neurobiological,
      genetic and pharmacological research of lifelong premature ejaculation (PE) have
      much contributed to a better understanding of the role of the central and
      peripheral nervous systems in mediating ejaculation. Research of genetic
      polymorphisms in men with lifelong PE and clinical research of the validity of
      the classification into four PE subtypes have provided a better insight into
      lifelong PE and its distinction from the three other PE subtypes. Nevertheless, a
      number of symptoms of lifelong PE and its treatment by SSRIs are still not well
      understood. In the current article, it will be argued that lifelong PE is
      characterized not only by early ejaculations (ejaculatio praecox), a diminished
      control over ejaculation, and negative personal consequences, but also by early
      erections (erectio praecox) and an immediately occurring detumescence of the
      penis after ejaculation (detumescentia praecox) as symptoms of an (sub)acute
      hypertonic or hypererotic physical state when making love. Based on animal
      research it is postulated that the facilitated erection, facilitated ejaculation
      and facilitated penile detumescence are associated with centrally and
      peripherally increased oxytocin release. In addition, it is postulated that
      mechano- and thermosensory activity of transient receptor potential (TRP) ion
      channels, located in skin receptors of the glans penis, are associated with
      lifelong PE. Research into the three characteristics of the (sub)acute
      hypererotic state will presumably contribute to a better phenomenological
      description of and better neurobiological understanding of lifelong PE and its
      delineation to the three other PE subtypes. 

PMID- 24333545
TI  - Health metrics for helminth infections.
AB  - Health metrics based on health-adjusted life years have become standard units for
      comparing the disease burden and treatment benefits of individual health
      conditions. The Disability-Adjusted Life Year (DALY) and the Quality-Adjusted
      Life Year (QALY) are the most frequently used in cost-effect analyses in national
      and global health policy discussions for allocation of health care resources.
      While sometimes useful, both the DALY and QALY metrics have limitations in their
      ability to capture the full health impact of helminth infections and other
      'neglected tropical diseases' (NTDs). Gaps in current knowledge of disease burden
      are identified, and interim approaches to disease burden assessment are
      discussed. 

PMID- 24333547
TI  - Antidepressant-related sexual dysfunction - perspectives from neuroimaging.
AB  - Sexual dysfunction is not only a common symptom in major depression but also a
      frequent side-effect of antidepressant medication, mainly of the selective
      serotonin reuptake-inhibitors (SSRI) that are often prescribed as a first line
      treatment option. Despite of the increasing incidence and prescription rates,
      neuronal mechanisms underlying SSRI-related sexual dysfunction are poorly
      understood and investigations on this topic are scarce. Neuroimaging techniques,
      mainly functional magnetic resonance imaging (fMRI), provide a feasible approach
      to investigate these mechanisms since SSRI-related sexual dysfunction is most
      likely related to central nervous processes. This review summarizes the recent
      literature regarding the basic clinical findings and imaging correlates of
      antidepressant-related sexual dysfunction linking brain regions and networks
      potentially involved to phases and subcomponents of sexual processing and
      antidepressant action. In particular, fMRI studies on SSRI antidepressants
      including paroxetine and SNRIs including bupropion are highlighted. 

PMID- 24333549
TI  - Inhibitory effect of Malvidin on TNF-alpha-induced inflammatory response in
      endothelial cells.
AB  - Vascular inflammatory responses are key mediators of endothelial dysfunction that
      leads to various pathologies in many diseases including atherosclerosis and
      cancer. The purpose of the study was to investigate the effects and molecular
      mechanisms of Malvidin, a natural pigment with strong antioxidant activity, on
      regulating inflammatory response in endothelial cells. Our results showed that
      tumor necrosis factor-alpha (TNF-alpha) significantly increased the protein or
      mRNA levels of monocyte chemotactic protein-1 (MCP-1), intercellular adhesion
      molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), whereas
      pretreatment with Malvidin inhibited TNF-alpha-induced increases of MCP-1, ICAM
      1, and VCAM-1 production in a concentration-dependent manner. In addition,
      Malvidin could inhibit degradation of IkappaBalpha and the nuclear translocation
      of p65, which suggesting the anti-inflammation mechanism of Malvidin by the
      nuclear factor kappa B (NF-kappaB) pathway. These results indicate the potential
      role of Malvidin in preventing chronic inflammation in many diseases. 

PMID- 24333548
TI  - Connecting the pathology of posttraumatic stress and substance use disorders:
      monoamines and neuropeptides.
AB  - Posttraumatic stress disorder (PTSD) co-occurs highly with substance use
      disorders (SUDs), yet the neurobiological basis for this comorbid relationship
      remains unclear. PTSD and SUDs result in similar pathological states including
      impulsive behavior, reward deficiency, and heightened stress sensitivity. Hence,
      PTSD and SUD may depend on overlapping dysfunctional neurocircuitry. Here we
      provide a short overview of the relationship between comorbid PTSD and SUD, as
      well as the potential role of select neurotransmitter systems that may underlie
      enhanced vulnerability to drug abuse in the context of PTSD. 

PMID- 24333550
TI  - Defining the role of NMDA receptors in anesthesia: are we there yet?
AB  - N-methyl-d-aspartate (NMDA) receptors are important in mediating excitatory
      neurotransmission in the nervous system. They are preferentially inhibited by
      some general anesthetics and have, therefore, been implied in the mediation of
      their effects. This review summarizes the main research findings available
      related to NMDA receptors and their role in anesthesia. The contribution of NMDA
      receptors to the anesthetized state is discussed separately for each of its
      components: amnesia, analgesia, unconsciousness and immobility. Anesthetic
      induced unconsciousness and immobility have received the most attention in the
      research community and are the main focus of this review. In the overall
      perspective, however, studies using pharmacological or electrophysiological
      approaches have failed to reach definitive conclusions regarding the contribution
      of NMDA receptors to these anesthetic endpoints. None of the studies have
      specifically addressed the role of NMDA receptors in the amnestic effect of
      general anesthetics, and the few available data are (at best) only indirect. NMDA
      receptor antagonism by general anesthetics may have a preventive anti
      hyperalgesic effect. The only and most extensively used genetic tool to examine
      the role of NMDA receptors in anesthesia is global knockout of the GluN2A subunit
      of the NMDA receptor. These animals are resistant to many intravenous and
      inhalational anesthetics, but the interpretation of their phenotype is hindered
      by the secondary changes occurring in these animals after GluN2A knockout, which
      are themselves capable of altering anesthetic sensitivity. Generation of more
      sophisticated conditional knockout models targeting NMDA receptors is required to
      finally define their role in the mechanisms of anesthesia. 

PMID- 24333551
TI  - Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a
      novel, investigational, orally active, small molecule gonadotropin-releasing
      hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice.
AB  - TAK-385 (relugolix) is a novel, non-peptide, orally active gonadotropin-releasing
      hormone (GnRH) antagonist, which builds on previous work with non-peptide GnRH
      antagonist TAK-013. TAK-385 possesses higher affinity and more potent
      antagonistic activity for human and monkey GnRH receptors compared with TAK-013.
      Both TAK-385 and TAK-013 have low affinity for the rat GnRH receptor, making them
      difficult to evaluate in rodent models. Here we report the human GnRH receptor
      knock-in mouse as a humanized model to investigate pharmacological properties of
      these compounds on gonadal function. Twice-daily oral administration of TAK-013
      (10mg/kg) for 4 weeks decreased the weights of testes and ventral prostate in
      male knock-in mice but not in male wild-type mice, demonstrating the validity of
      this model to evaluate antagonists for the human GnRH receptor. The same dose of
      TAK-385 also reduced the prostate weight to castrate levels in male knock-in
      mice. In female knock-in mice, twice-daily oral administration of TAK-385
      (100mg/kg) induced constant diestrous phases within the first week, decreased the
      uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in
      the pituitary after 4 weeks. Gonadal function of TAK-385-treated knock-in mice
      began to recover after 5 days and almost completely recovered within 14 days
      after drug withdrawal in both sexes. Our findings demonstrate that TAK-385 acts
      as an antagonist for human GnRH receptor in vivo and daily oral administration
      potently, continuously and reversibly suppresses the hypothalamic-pituitary
      gonadal axis. TAK-385 may provide useful therapeutic interventions in hormone
      dependent diseases including endometriosis, uterine fibroids and prostate cancer.

PMID- 24333553
TI  - Polymer dots for quantifying the total hydrophobic pathogenic lysates in a single
      drop.
AB  - A selective, rapid, small sample load (2-4 MUL), and sensitive quantification
      method for the hydrophobic cellular biomolecules of pathogenic bacteria and their
      biosensing application were reported. The present approach is based on using
      polythiophene polymer dots (2.5 nm), which were prepared via the
      oxidation/polymerization reactions and then were characterized using transmission
      electron microscopy (TEM), Fourier transform infrared (FT-IR), ultraviolet
      spectroscopy (UV), and matrix (surface) assisted laser desorption/ionization mass
      spectrometry (M(S)ALDI-MS). The present method requires only gentle agitation for
      a single drop of aqueous bacteria suspension (10 MUL, Pseudomonas aeruginosa
      (1*10(4) cfu/mL) and Staphylococcus aureus (1*10(5) cfu/mL)) with 1 mL of
      polythiophene (0.5 mg/mL) in chloroform, and the time required for quantifying
      the total hydrophobic was significantly reduced to less than 3 min. The
      polythiophene polymer dots is also a quantitative assessment of bacteria for
      aqueous and blood samples if exposed to more than 4-5 MUL of pathogenic bacteria
      and thus, it is a new biosensor for quantitative hydrophobic portions. The
      fluorescence intensity of polythiophene was enhanced after adding different
      volumes of pathogenic bacteria with low colony units. The standard bacteria
      suspensions of P. aeruginosa and S. aureus have low LOD (limits of detection) for
      2 MUL (1*10(4) cfu/mL) and 4 MUL (1*10(5) cfu/mL), respectively. Further, the
      pathogenic bacteria were spiked into mouse blood and the total hydrophobic
      biomolecules were quantified. This method is extremely rapid as it does not
      require any culture steps prior to analysis and also no need for any separation
      or post sample treatments.

PMID- 24333554
TI  - Use of ginsenoside Rg3-loaded electrospun PLGA fibrous membranes as wound cover
      induces healing and inhibits hypertrophic scar formation of the skin.
AB  - Prevention of hypertrophic scar formation of the skin requires a complex
      treatment process, which mainly includes promoting skin regeneration in an early
      stage while inhibiting hypertrophic formation in a later stage. Electrospinning
      PLGA with the three-dimensional micro/nano-fibrous structure and as drugs
      carrier, could be used as an excellent skin repair scaffold. However, it is
      difficult to combine the advantage of nanofibrous membranes and drug carriers to
      achieve early and late treatment. In this study, Ginsenoside-Rg3 (Rg3) loaded
      hydrophilic poly(D,L-lactide-co-glycolide) (PLGA) electrospun fibrous membranes
      coated with chitosan (CS) were fabricated by combining electrospinning and
      pressure-driven permeation (PDP) technology. The PDP method was able to
      significantly improve the hydrophilicity of electrospun fibrous membranes through
      surface coating of the hydrophilic fibers with CS, while maintaining the Rg3
      releasing rate of PLGA electrospun fibrous membranes. Experimental wounds of
      animal covered with PDP treated fibrous membranes completely re-epithelialized
      and healed 3-4 days earlier than the wounds in control groups. Scar elevation
      index (SEI) measurements and histologic characteristics revealed that Rg3
      significantly inhibited scar formation 28 days post-surgery. Moreover, RT-PCR
      assays and western blot analysis revealed that at day 28 after wound induction
      the expression of VEGF, mRNA and Collagen Type I in the scars treated with Rg3
      was decreased compared to control groups. Taken together PLGA-Rg3/CS electrospun
      fibrous membranes induced repair of tissue damage in the early stage and
      inhibited scar formation in the late stage of wound healing. These dual
      functional membranes present a combined therapeutic approach for inhibiting
      hypertrophic scars of the skin.

PMID- 24333552
TI  - Mobilizing endogenous stem cells for retinal repair.
AB  - Irreversible vision loss is most often caused by the loss of function and
      subsequent death of retinal neurons, such as photoreceptor cells-the cells that
      initiate vision by capturing and transducing signals of light. One reason why
      retinal degenerative diseases are devastating is that, once retinal neurons are
      lost, they don't grow back. Stem cell-based cell replacement strategy for retinal
      degenerative diseases are leading the way in clinical trials of transplantation
      therapy, and the exciting findings in both human and animal models point to the
      possibility of restoring vision through a cell replacement regenerative approach.
      A less invasive method of retinal regeneration by mobilizing endogenous stem
      cells is, thus, highly desirable and promising for restoring vision. Although
      many obstacles remain to be overcome, the field of endogenous retinal repair is
      progressing at a rapid pace, with encouraging results in recent years.

PMID- 24333555
TI  - Experimental and theoretical approach to cationic drug-anionic gemini surfactant
      systems in aqueous medium.
AB  - Herein the results of surface tension measurements on the mixed systems of an
      amphiphilic drug amitriptyline hydrochloride (AMT) and three anionic
      bisphosphodiester gemini surfactants having different hydrophobic tails (8, 10,
      and 12 carbon) are presented. The experimental and ideal critical micelle
      concentration (cmc and cmcid) values suggest synergism in mixed systems of AMT
      and 8-2-8/10-2-10 and attractive interaction in AMT-12-2-12 systems. Other
      parameters evaluated from the data also suggest mixed micellization among the
      components with almost 50% contribution of surfactants (micellar mole fraction,
      X1(m), close to 0.5). The X1 values evaluated from Rubingh's model (X1(m)) and
      Motomura's model (X1(M)) as well as X1(id) values increase with increasing
      content of surfactants in solution. Adsorption behavior too indicates that the
      mixed monolayers experience attractive interaction (beta(sigma)) which vary in
      the order: AMT-12-2-12<AMT-8-2-8<AMT-10-2-10. Interaction in mixed micelles
      (beta(m)) follows the same trend. The results suggest that mixed systems of AMT
      10-2-10 are the most stable one. Probably the difference in length of hydrophobic
      parts of AMT and gemini is most compatible in this system. 

PMID- 24333556
TI  - Selective blocking of primary amines in branched polyethylenimine with
      biocompatible ligand alleviates cytotoxicity and augments gene delivery efficacy
      in mammalian cells.
AB  - Recently, polyethylenimines (PEIs) have emerged as efficient vectors for nucleic
      acids delivery. However, inherent cytotoxicity has limited their in vivo
      applications. To address this concern as well as to incorporate hydrophobic
      domains for improving interactions with the lipid bilayers in the cell membranes,
      we have tethered varying amounts of amphiphilic pyridoxyl moieties onto bPEI to
      generate a small series of pyridoxyl-PEI (PyP) polymers. Spectroscopic
      characterization confirms the formation of PyP polymers, which subsequently form
      stable complexes with pDNA in nanometric range with positive surface charge. The
      projected modification not only accounts for a decrease in the density of 1
      degrees  amines but also allows formation of relatively loose complexes with pDNA
      (cf. bPEI). Alleviation of the cytotoxicity, efficient interaction with cell
      membranes and easy disassembly of the pDNA complexes have led to the remarkable
      enhancement in the transfection efficiency of PyP/pDNA complexes in mammalian
      cells with one of the formulations, PyP-3/pDNA complex, showing transfection in
      ~68% cells compared to ~16% cells by Lipofectamine/pDNA complex. Further, the
      efficacy of PyP-3 vector has been established by delivering GFP-specific siRNA
      resulting in ~88% suppression of the target gene expression. These results
      demonstrate the efficacy of the projected carriers that can be used in future
      gene therapy applications. 

PMID- 24333557
TI  - Ascorbyl palmitate/DSPE-PEG nanocarriers for oral iron delivery: preparation,
      characterisation and in vitro evaluation.
AB  - The objective of this study was to encapsulate iron in nanocarriers formulated
      with ascorbyl palmitate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine
      polyethylene glycol (DSPE-PEG) for oral delivery. Blank and iron (Fe) loaded
      nanocarriers were prepared by a modified thin film method using ascorbyl
      palmitate and DSPE-PEG. Surface charge of the nanocarriers was modified by the
      inclusion of chitosan (CHI) during the formulation process. Blank and iron loaded
      ascorbyl palmitate/DSPE nanocarriers were visualised by transmission electron
      microscopy (TEM) and physiochemical characterisations of the nanocarriers carried
      out to determine the mean particle size and zeta potential. Inclusion of chitosan
      imparted a net positive charge on the nanocarrier surface and also led to an
      increase in mean particle size. Iron entrapment in ascorbyl palmitate-Fe and
      ascorbyl palmitate-CHI-Fe nanocarriers was 67% and 76% respectively, suggesting a
      beneficial effect of chitosan on nanocarrier Fe entrapment. Iron absorption was
      estimated by measuring Caco-2 cell ferritin formation using ferrous sulphate as a
      reference standard. Iron absorption from ascorbyl palmitate-Fe (592.17+/-21.12
      ng/mg cell protein) and ascorbyl palmitate-CHI-Fe (800.12+/-47.6 ng/mg, cell
      protein) nanocarriers was 1.35-fold and 1.5-fold higher than that from free
      ferrous sulphate, respectively (505.74+/-23.73 ng/mg cell protein) (n=6, p<0.05).
      This study demonstrates for the first time preparation and characterisation of
      iron loaded ascorbyl palmitate/DSPE PEG nanocarriers, and that engineering of the
      nanocarriers with chitosan leads to a significant augmentation of iron
      absorption.

PMID- 24333558
TI  - The energy transfer based fluorescent approach to detect the formation of silica
      supported phosphatidylcholine and phosphatidylserine containing bilayers.
AB  - The work introduces the quenching of silica coated Tb(III) complexes by
      merocyanine 540 (MC540) and copper ions as a tool to reveal the adsorption of
      phosphatidylcholine (PC) and phosphatidylserine (PS) at various PS:PC ratio onto
      silica nanoparticles doped with Tb(III) complex. The binding of MC540 with PC
      based bilayers and copper ions with PS-based ones are the basis of their use as
      organic and inorganic probes to sense PS:PC ratio in silica supported mixed
      bilayers. The enrichment of mixed bilayers by PS results in the displacement of
      MC540 anions, while it enhances the binding with copper ions. The displacement or
      binding of probe ions results in the diverse luminescence response of Tb(III)
      centred luminescence. The reestablishment of the steady state and time resolved
      luminescence is observed, when MC540 anions are applied as probes. The use of
      copper ions as probes results in the opposite quenching effect. The developed
      route enables to discriminate the formation of the phospholipids bilayers onto
      silica surface from those in the bulk of solution under various concentration
      conditions. 

PMID- 24333559
TI  - Effect of ultrasound on cyprid footprint and juvenile barnacle adhesion on a
      fouling release material.
AB  - In our earlier studies, we have demonstrated that low and high intensity
      ultrasound can prevent barnacle cyprid settlement. In this study, we found that
      ultrasound treatment reduced the adhesion of newly metamorphosed barnacles up to
      2 days' old. This was observed in the reduction of adhesion strength of the newly
      settled barnacles from ultrasound treated cyprids on silicone substrate compared
      to the adhesion strength of barnacles metamorphosed from cyprids not exposed to
      ultrasound. Atomic force microscopy (AFM) was used to analyze the effect of
      ultrasound on barnacle cyprid footprints (FPs), which are protein adhesives
      secreted when the larvae explore surfaces. The ultrasound treated cyprids were
      found to secrete less FPs, which appeared to spread a larger area than those
      generated by untreated cyprids. The evidence from this study suggests that
      ultrasound treatment results in a reduced cyprid settlement and footprint
      secretion, and may affect the subsequent recruitment of barnacles onto fouling
      release surfaces by reducing the ability of early settlement stage of barnacles
      (up to 2 days' old) from firmly adhering to the substrates. Ultrasound therefore
      can be used in combination with fouling release coatings to offer a more
      efficient antifouling strategy. 

PMID- 24333560
TI  - Clinical value of plasma pentraxin 3 levels for predicting cardiac troponin
      elevation after percutaneous coronary intervention.
AB  - AIMS: Post-procedural myocardial necrosis manifested by elevated cardiac troponin
      T (cTnT) often complicates percutaneous coronary intervention (PCI). Plasma
      pentraxin 3 (PTX3) levels are increased in patients with arterial inflammation
      and especially unstable angina pectoris (UAP). This study tested whether plasma
      PTX3 levels can predict post-PCI cTnT elevation. MAIN METHODS: We evaluated 94
      consecutive patients with AP and normal pre-PCI cTnT levels who underwent PCI.
      Pre-PCI virtual histology-intravascular ultrasound was performed to assess
      culprit plaque composition. Plasma PTX3 and serum hs-CRP levels were measured pre
      PCI. Patients were divided into 2 groups according to presence (Group I, n=34) or
      absence (Group II, n=60) of post-PCI cTnT elevation >3 * the upper limit of
      normal at 24h after PCI. KEY FINDINGS: Plasma PTX3 (4.06 +/- 2.05 ng/ml vs 2.17
      +/- 1.02 ng/ml, p<0.001), serum hs-CRP levels (0.25 +/- 0.03 vs 0.16 +/- 0.03
      mg/dl, p=0.048), plaque burden (80.9 +/- 5.3 vs 75.4 +/- 10.6%, p=0.047),
      presence of positive remodeling (59 vs 25%, p=0.034), and percent necrotic core
      area (19.0 +/- 7.4 vs 14.0 +/- 5.9%, p=0.046) were significantly higher in Group
      I than in Group II. Receiver-operating characteristic curve analysis showed that
      with a best cut-off value of 2.83 ng/ml, plasma PTX3 level (AUC 0.823) predicted
      post-PCI cardiac TnT elevation better than did serum hs-CRP level (AUC 0.618).
      Multiple logistic regression analysis showed that plasma PTX3 level was the most
      independent predictor of post-PCI cardiac cTnT elevation (OR: 2.65; 95% CI: 1.56
      10.1; p=0.003). SIGNIFICANCE: Plasma PTX3 level may be a useful marker for
      predicting post-PCI cardiac cTnT elevation, which is associated with inflammatory
      status of culprit lesions.

PMID- 24333561
TI  - Cardioprotective mechanism of S-nitroso-N-acetylcysteine via S-nitrosated
      betadrenoceptor-2 in the LDLr-/- mice.
AB  - Previous studies from our group have demonstrated the protective effect of S
      nitroso-N-acetylcysteine (SNAC) on the cardiovascular system in dyslipidemic LDLr
      /- mice that develop atheroma and left ventricular hypertrophy after 15 days on a
      high fat diet. We have shown that SNAC treatment attenuates plaque development
      via the suppression of vascular oxidative stress and protects the heart from
      structural and functional myocardial alterations, such as heart arrhythmia, by
      reducing cardiomyocyte sensitivity to catecholamines. Here we investigate the
      ability of SNAC to modulate oxidative stress and cell survival in cardiomyocytes
      during remodeling and correlation with beta2-AR signaling in mediating this
      protection. Ventricular superoxide (O2-) and hydrogen peroxide (H2O2) generation
      was measured by HPLC methods to allow quantification of dihydroethidium (DHE)
      products. Ventricular histological sections were stained using terminal dUTP nick
      end labeling (TUNEL) to identify nuclei with DNA degradation (apoptosis) and this
      was confirmed by Western blot for cleaved caspase-3 and caspase-7 protein
      expression. The findings show that O2- and H2O2 production and also cell
      apoptosis were increased during left ventricular hypertrophy (LVH). SNAC
      treatment reduced oxidative stress during on cardiac remodeling, measured by
      decreased H2O2 and O2- production (65% and 52%, respectively), and a decrease in
      the ratio of p-Ser1177 eNOS/total eNOS. Left ventricle (LV) from SNAC-treated
      mice revealed a 4-fold increase in beta2-AR expression associated with coupling
      change to Gi; beta2-ARs-S-nitrosation (beta2-AR-SNO) increased 61%, while
      apoptosis decreased by 70%. These results suggest that the cardio-protective
      effect of SNAC treatment is primarily through its anti-oxidant role and is
      associated with beta2-ARs overexpression and beta2-AR-SNO via an anti-apoptotic
      pathway.

PMID- 24333562
TI  - Role of metabolic environment on nitric oxide mediated inhibition of neointimal
      hyperplasia in type 1 and type 2 diabetes.
AB  - Nitric oxide (NO) is well known to inhibit neointimal hyperplasia following
      arterial injury. Previously, we reported that NO was more effective at inhibiting
      neointimal hyperplasia in a type 2 diabetic environment than control. We also
      found that NO was ineffective in an uncontrolled type 1 diabetic environment;
      however, insulin restored the efficacy of NO. Thus, the goal of this study was to
      more closely evaluate the effect of insulin and glucose on the efficacy of NO at
      inhibiting neointimal hyperplasia in both type 1 and type 2 diabetic environments
      using different doses of insulin as well as pioglitazone. Type 1 diabetes was
      induced in male lean Zucker (LZ) rats with streptozotocin (60 mg/kg IP). Groups
      included control, moderate glucose control, and tight glucose control. Zucker
      diabetic fatty (ZDF) rats fed Purina 5008 chow were used as a type 2 diabetic
      model. Groups included no therapy, insulin therapy, or pioglitazone therapy.
      After 4 weeks of maintaining group assignments, the carotid artery injury model
      was performed. Treatment groups included: control, injury and injury plus NO. 2
      weeks following arterial injury, in the type 1 diabetic rats, NO most effectively
      reduced the neointimal area in the moderate and tightly controlled groups (81%
      and 88% vs. 33%, respectively, p=0.01). In type 2 diabetic rats, the metabolic
      environment had no impact on the efficacy of NO (81-82% reduction for all
      groups). Thus, in this study, we show NO is effective at inhibiting neointimal
      hyperplasia in both type 1 and type 2 diabetic environments. A greater
      understanding of how the metabolic environment may impact the efficacy of NO may
      lead to the development of more effective NO-based therapies for patients with
      diabetes.

PMID- 24333563
TI  - A comparative study of NONOate based NO donors: spermine NONOate is the best
      suited NO donor for angiogenesis.
AB  - Nitric oxide (NO) is a known modulator of angiogenesis. The NONOate subfamily of
      NO donors has long been used in experimental and clinical studies to promote
      angiogenesis. However, no studies have been conducted yet to compare the
      angiogenesis potential of these NO donors in respect to their pattern of NO
      release. We hypothesize that having different pattern of NO release, each of the
      NO donors in NONOate subfamily can promote key stages of angiogenesis in
      differential manner. To verify our hypothesis, NO donors with half life ranging
      from seconds to several hours and having very different pattern of NO release
      were selected to evaluate their efficacy in modulating angiogenesis. Endothelial
      tube formation using EAhy926 cells was maximally increased by Spermine NONOate
      (SP) treatment. SP treatment maximally induced both ex vivo and in vivo
      angiogenesis using egg yolk and cotton plug angiogenesis models respectively.
      Experiment using chick embryo partial ischemia model revealed SP as the best
      suited NO donor to recover ischemia driven hampered angiogenesis. The present
      study elaborated that differential release pattern of NO by different NO donors
      can modulate angiogenesis differentially and also suggested that SP have a unique
      pattern of NO release that best fits for angiogenesis. 

PMID- 24333564
TI  - Nitric oxide in the commissural nucleus tractus solitarii regulates carotid
      chemoreception hyperglycemic reflex and c-Fos expression.
AB  - Carotid body chemoreceptors function as glucose sensors and contribute to glucose
      homeostasis. The nucleus tractus solitarii (NTS) is the first central nervous
      system (CNS) nuclei for processing of information arising in the carotid body.
      Here, we microinjected a nitric oxide (NO) donor sodium nitroprusside (SNP), an
      NO-independent activator of the soluble guanylyl cyclase (sGC) (YC1) or an NO
      synthase (NOS) inhibitor Nomega-nitro-l-arginine methyl ester (L-NAME) into the
      commissural NTS (cNTS) before carotid chemoreceptor anoxic stimulation and
      measured arterial glucose and the expression of Fos-like immunoreactivity (Fos
      ir). Male Wistar rats (250-300 g) were anesthetized, and the carotid sinus was
      vascularly isolated. Either artificial cerebrospinal fluid (aCSF), SNP, YC1 or L
      NAME were stereotaxically injected into the cNTS. The SNP and YC1 infused into
      the cNTS before carotid chemoreceptor stimulation (SNP-2 and YC1-2 groups)
      similarly increased arterial glucose compared to the aCSF-2 group. By contrast,
      infusion of L-NAME into the cNTS before carotid chemoreceptor stimulation (L-NAME
      2 group) decreased arterial glucose concentration. The number of cNTS Fos-ir
      neurons, determined in all the groups studied except for YC1 groups,
      significantly increased in SNP-2 rat when compared to the aCSF-2 or SNP-2 groups.
      Our findings demonstrate that NO signaling, and the correlative activation of
      groups of cNTS neurons, plays key roles in the hyperglycemic reflex initiated by
      carotid chemoreceptor stimulation.

PMID- 24333565
TI  - Prostaglandin D(2) is crucial for seizure suppression and postictal sleep.
AB  - Epilepsy is a neurological disorder with the occurrence of seizures, which are
      often accompanied by sleep. Prostaglandin (PG) D2 is produced by hematopoietic or
      lipocalin-type PGD synthase (H- or L-PGDS) and involved in the regulation of
      physiological sleep. Here, we show that H-PGDS, L/H-PGDS or DP1 receptor (DP1R)
      KO mice exhibited more intense pentylenetetrazole (PTZ)-induced seizures in terms
      of latency of seizure onset, duration of generalized tonic-clonic seizures, and
      number of seizure spikes. Seizures significantly increased the PGD2 content of
      the brain in wild-type mice. This PTZ-induced increase in PGD2 was attenuated in
      the brains of L- or H-PGDS KO and abolished in L/H-PGDS KO mice. Postictal non
      rapid eye movement sleep was observed in the wild-type and H-PGDS or DP2R KO, but
      not in the L-, L/H-PGDS or DP1R KO, mice. These findings demonstrate that PGD2
      produced by H-PGDS and acting on DP1R is essential for seizure suppression and
      that the L-PGDS/PGD2/DP1R system regulates sleep that follows seizures. 

PMID- 24333566
TI  - A simple synthesis of 2-keto-3-deoxy-D-erythro-hexonic acid isopropyl ester, a
      key sugar for the bacterial population living under metallic stress.
AB  - 2-Keto-3-deoxy-D-erythro-hexonic acid (KDG) is the key intermediate metabolite of
      the Entner Doudoroff (ED) pathway. A simple, efficient and stereoselective
      synthesis of KDG isopropyl ester is described in five steps from 2,3-O
      isopropylidene-D-threitol with an overall yield of 47%. KDG isopropyl ester is
      studied as an attractive marker of a functional Entner Doudoroff pathway. KDG
      isopropyl ester is used to promote growth of ammonium producing bacterial
      strains, showing interesting features in the remediation of heavy-metal polluted
      soils.

PMID- 24333567
TI  - A methylation-blocked cascade amplification strategy for label-free colorimetric
      detection of DNA methyltransferase activity.
AB  - DNA methyltransferase (MTase), catalyzing DNA methylation in both eukaryotes and
      prokaryotes, is closely related with cancer and bacterial diseases. Although
      there are various methods focusing on DNA MTase detection, most of them share
      common defects such as complicated setup, laborious operation and requirement of
      expensive analytical instruments. In this work, a simple strategy based on
      methylation-blocked cascade amplification is developed for label-free
      colorimetric assay of MTase activity. When DNA adenine methylation (Dam) MTase is
      introduced, the hairpin probe is methylated. This blocks the amplified generation
      of G-riched DNAzyme by nicking endonuclease and DNA polymerase, and inhibits the
      DNAzyme-catalyzed colorimetric reaction. Contrarily, an effective colorimetric
      reaction is initiated and high color signal is clearly observed by the naked eye
      in the absence of Dam MTase. A satisfying sensitivity and high selectivity are
      readily achieved within a short assay time of 77 min, which are superior to those
      of some existing approaches. Additionally, the application of the sensing system
      in human serum is successfully verified with good recovery and reproducibility,
      indicating great potential for the practicality in high concentrations of
      interfering species. By using several anticancer and antimicrobial drugs as
      model, the inhibition of Dam MTase is well investigated. Therefore, the proposed
      method is not only promising and convenient in visualized analysis of MTase, but
      also useful for further application in fundamental biological research, early
      clinical diagnosis and drug discovery.

PMID- 24333568
TI  - A field effect transistor biosensor with a gamma-pyrone derivative engineered
      lipid-sensing layer for ultrasensitive Fe3+ ion detection with low pH
      interference.
AB  - Field effect transistors have risen as one of the most promising techniques in
      the development of biomedical diagnosis and monitoring. In such devices, the
      sensitivity and specificity of the sensor rely on the properties of the active
      sensing layer (gate dielectric and probe layer). We propose here a new type of
      transistor developed for the detection of Fe(3+) ions in which this sensing layer
      is made of a monolayer of lipids, engineered in such a way that it is not
      sensitive to pH in the acidic range, therefore making the device perfectly
      suitable for biomedical diagnosis. Probes are gamma-pyrone derivatives that have
      been grafted to the lipid headgroups. Affinity constants derived for the
      chelator/Fe(3+) complexation as well as for other ions demonstrate very high
      sensitivity and specificity towards ferric ions with values as high as 5.10(10) M
      and a detected concentration as low as 50 fM.

PMID- 24333569
TI  - Visual detection of microRNA with lateral flow nucleic acid biosensor.
AB  - We report a DNA-gold nanoparticle (DNA-GNP) based lateral flow nucleic acid
      biosensor for visual detection of microRNA (miRNA)-215 in aqueous solutions and
      biological samples with low-cost and short analysis time. Sandwich-type
      hybridization reactions among GNP-labeled DNA probe, miRNA-215 and biotin
      modified DNA probes were performed on the lateral flow device. The accumulation
      of GNPs on the test zone of the biosensor enables the visual detection of miRNA
      215. After systematic optimization, the biosensor was able to detect a minimum
      concentration of 60 pM miRNA-215. The biosensor was applied to detect miRNA-215
      from A549 cell lysate directly without complex sample treatment, and the
      detection limit of 0.148 million cells was obtained. This study provides a
      simple, rapid, specific and low-cost approach for miRNA detection in aqueous
      solutions and biological samples, showing great promise for clinical application
      and biomedical diagnosis in some malignant diseases.

PMID- 24333570
TI  - Advances in paper-based point-of-care diagnostics.
AB  - Advanced diagnostic technologies, such as polymerase chain reaction (PCR) and
      enzyme-linked immunosorbent assay (ELISA), have been widely used in well-equipped
      laboratories. However, they are not affordable or accessible in resource-limited
      settings due to the lack of basic infrastructure and/or trained operators. Paper
      based diagnostic technologies are affordable, user-friendly, rapid, robust, and
      scalable for manufacturing, thus holding great potential to deliver point-of-care
      (POC) diagnostics to resource-limited settings. In this review, we present the
      working principles and reaction mechanism of paper-based diagnostics, including
      dipstick assays, lateral flow assays (LFAs), and microfluidic paper-based
      analytical devices (MUPADs), as well as the selection of substrates and
      fabrication methods. Further, we report the advances in improving detection
      sensitivity, quantification readout, procedure simplification and multi
      functionalization of paper-based diagnostics, and discuss the disadvantages of
      paper-based diagnostics. We envision that miniaturized and integrated paper-based
      diagnostic devices with the sample-in-answer-out capability will meet the diverse
      requirements for diagnosis and treatment monitoring at the POC. 

PMID- 24333571
TI  - Label-free colorimetric assay for base excision repair enzyme activity based on
      nicking enzyme assisted signal amplification.
AB  - Specific and sensitive detection of base excision repair enzyme activity is
      essential to many fundamental biochemical process researches. Here, we propose a
      novel label-free homogeneous strategy for visualized uracil DNA glycosylase (UDG)
      activity assay based on nicking enzyme assisted signal amplification. In this
      method two hairpin probes were employed for the colorimetric detection, namely
      hairpin probe 1 (HP 1) carrying two uracil residues in the stem, and hairpin
      probe 2 (HP 2) containing a G-riched DNAzyme segment, and the recognition
      sequence as well as the cleavage site for the nicking enzyme. In the presence of
      UDG, the uracil bases in the stem of HP 1 can be specifically recognized and
      hydrolyzed by UDG, which leads to the destabilization of its stem containing
      abasic sites (AP sites), and then results in the opening of HP 1 to form a single
      strand. The opened HP 1 hybridizes with HP 2 to form a DNA duplex, which
      initiates the specific cleavage of HP 2 by the nicking enzyme, leading to the
      release of G-riched DNAzyme segments. As a result, HP 1 is released and able to
      hybridize with another HP 2 to induce the continuous cleavage of HP 2, generating
      enormous amount of G-riched DNAzyme segments. Finally, the G-riched DNAzyme
      segments bind hemin to form a catalytically active G-quadruplex-hemin DNAzyme
      which can catalyze the H2O2-mediated oxidation of 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS(2-)) to the colored ABTS(-),
      providing a visible signal for UDG activity detection. This assay exhibits
      several advantages such as simplicity, low-cost, high selectivity and desirable
      sensitivity, which shows great potential of providing a promising platform for
      convenient and visualized analysis of UDG or other biomolecules. 

PMID- 24333573
TI  - Differential role of the basolateral amygdala 5-HT3 and 5-HT4 serotonin receptors
      upon ACPA-induced anxiolytic-like behaviors and emotional memory deficit in mice.
AB  - BACKGROUND AND AIM: The critical role of cannabinoidergic and serotonergic
      systems of the amygdala in modulation of anxiety-like behaviors and emotional
      memory has already been demonstrated. The present study aimed to investigate the
      possible role of the basolateral amygdala (BLA) 5-HT3 and 5-HT4 serotonergic
      systems upon ACPA (CB1 cannabinoid receptor agonist)-induced anxiolytic-like
      behaviors and emotional memory impairment using the elevated plus-maze (EPM) test
      retest paradigm in male mice. METHOD: bilateral guide-cannulae were implanted to
      allow intra-BLA microinjection of serotonergic agents. RESULTS: the
      intraperitoneal injection of ACPA could induce anxiolytic-like behaviors and
      reduce the emotional memory formation. Intra-BLA injection of M
      Chlorophenylbiguanide (M-Chl, a 5-HT3 serotonin receptor agonist) neither altered
      the anxiety-like behaviors nor the emotional memory formation by itself, while
      the higher dose of Y-25130 (a 5-HT3 serotonin receptor antagonist) reduced the
      emotional memory formation and locomotor activity but not the anxiety-like
      behaviors. Furthermore, injection of a higher dose of RS67333 and RS23597 (as 5
      HT4 serotonin receptor agonist and antagonist, respectively) did not alter the
      anxiety-like behaviors, while reduced the emotional memory formation. In
      addition, the intra-BLA injection of M-Chl but not Y-25130 and RS67333 restored
      the ACPA-induced anxiolytic-like behaviors and emotional memory deficit, while a
      higher dose of RS67333 decreased the locomotor activity. Moreover, the intra-BLA
      microinjection of RS23597 could restore the ACPA-induced anxiolytic-like
      behaviors but not the emotional memory deficit. CONCLUSION: based on our
      findings, ACPA seems to induce its anxiolytic-like behaviors and emotional memory
      formation deficits via activation and deactivation of the BLA 5-HT4 and 5-HT3
      serotonin receptors.

PMID- 24333572
TI  - In vivo suppression of NK cell cytotoxicity by stress and surgery:
      glucocorticoids have a minor role compared to catecholamines and prostaglandins.
AB  - Most in vitro and ex-vivo studies indicate a profound suppression of NK cell
      cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins
      were reported both to suppress and to enhance NKCC. However, methodological
      considerations hinder our ability to deduce from these findings to the impact of
      endogenous release of these factors on in vivo levels of NKCC and their
      implications to NK-dependent resistance to pathologies in living humans or
      animals. Here we used an in vivo approach that sensitively and specifically
      reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor
      cells (MADB106), and based on comparing effects between NK-intact and NK-depleted
      rats. To study the role of corticosterone, epinephrine, and prostaglandins, we
      administered these factors to rats, or antagonized their endogenous release
      following different stress paradigms or surgery. The results indicated that
      endogenous or exogenous elevated corticosterone levels can suppress in vivo NKCC
      levels, but only under some conditions, and mostly secondarily to the NK
      suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC
      suppression occurred (i) only under prolonged, but not short exposure to stress,
      and mainly in males; (ii) was smaller than the prominent impact of epinephrine;
      (iii) was mostly ascribed to corticosterone-induced potentiation of the effects
      of epinephrine or/and prostaglandins; and (iv) was completely abolished through
      antagonizing epinephrine or/and prostaglandins. Overall, these findings markedly
      limit the significance of stress/surgery-induced corticosterone release in the in
      vivo suppression of NKCC, and highlight the blockade of epinephrine or/and
      prostaglandins as effective and clinically feasible approaches to overcome such
      immuno-suppressive effects. 

PMID- 24333574
TI  - An automated maze task for assessing hippocampus-sensitive memory in mice.
AB  - Memory deficits associated with hippocampal dysfunction are a key feature of a
      number of neurodegenerative and psychiatric disorders. The discrete-trial
      rewarded alternation T-maze task is highly sensitive to hippocampal dysfunction.
      Normal mice have spontaneously high levels of alternation, whereas hippocampal
      lesioned mice are dramatically impaired. However, this is a hand-run task and
      handling has been shown to impact crucially on behavioural responses, as well as
      being labour-intensive and therefore unsuitable for high-throughput studies. To
      overcome this, a fully automated maze was designed. The maze was attached to the
      mouse's home cage and the subject earned all of its food by running through the
      maze. In this study the hippocampal dependence of rewarded alternation in the
      automated maze was assessed. Bilateral hippocampal-lesioned mice were assessed in
      the standard, hand-run, discrete-trial rewarded alternation paradigm and in the
      automated paradigm, according to a cross-over design. A similarly robust lesion
      effect on alternation performance was found in both mazes, confirming the
      sensitivity of the automated maze to hippocampal lesions. Moreover, the
      performance of the animals in the automated maze was not affected by their
      handling history whereas performance in the hand-run maze was affected by prior
      testing history. By having more stable performance and by decreasing human
      contact the automated maze may offer opportunities to reduce extraneous
      experimental variation and therefore increase the reproducibility within and/or
      between laboratories. Furthermore, automation potentially allows for greater
      experimental throughput and hence suitability for use in assessment of cognitive
      function in drug discovery. 

PMID- 24333575
TI  - Autistic-like behavioural and neurochemical changes in a mouse model of food
      allergy.
AB  - Food allergy has been suggested to contribute to the expression of psychological
      and psychiatric traits, including disturbed social behaviour and repetitive
      behaviour inherent in autism spectrum disorders (ASD). Most research in this
      field receives little attention, since fundamental evidence showing direct
      effects of food allergic immune responses on social behaviour is very limited. In
      the present study, we show that a food allergic reaction to cow's milk protein,
      induced shortly after weaning, reduced social behaviour and increased repetitive
      behaviour in mice. This food allergic reaction increased levels of serotonin (5
      hydroxytryptamine; 5-HT) and the number of 5-HT positive cells, and decreased
      levels of 5-hydroxyindoleacetic acid (5-HIAA) in the intestine. Behavioural
      changes in food allergic mice were accompanied by reduced dopaminergic activity
      in the prefrontal cortex. Furthermore, neuronal activation (c-Fos expression) was
      increased in the prefrontal cortex and reduced in the paraventricular nucleus of
      the hypothalamus after exposure to a social target. We hypothesize that an
      intestinal allergic response regulates complex, but critical, neuroimmune
      interactions, thereby affecting brain circuits involved in social interaction,
      repetitive behaviour and cognition. Together with a genetic predisposition and
      multiple environmental factors, these effects of allergic immune activation may
      exacerbate behavioural abnormalities in patients with ASD. 

PMID- 24333577
TI  - Disentangling the relationship between epilepsy and its behavioral comorbidities 
      the need for prospective studies in new-onset epilepsies.
AB  - It has been long recognized that there is more to epilepsy than seizures. The
      prevalence of such neurobehavioral abnormalities as cognitive and mood disorders,
      autism spectrum disorder, and attention deficit and hyperactivity disorder (ADHD)
      is significantly higher among patients with epilepsy than in the general
      population. A long-held view that comorbidities of epilepsy represent mere
      epiphenomena of seizures has undergone substantial transformation during the past
      decade, as emerging clinical evidence and experimental evidence suggest the
      involvement of specific neurobiological mechanisms in the evolution of
      neurobehavioral deficits in patients with epilepsy. Developmental aspects of both
      epilepsy and its comorbidities, as well as the frequently reported reciprocal
      connection between these disorders, both add other dimensions to the already
      complex problem. In light of progress in effective seizure management in many
      patients with epilepsy, the importance of neurobehavioral comorbidities has
      become acute, as the latter are frequently more detrimental to patients' quality
      of life compared with seizures. This calls for a serious increase in efforts to
      effectively predict, manage, and ideally cure these comorbidities. Coordinated
      multicenter clinical, translational, and basic research studies focusing on
      epidemiology, neuropsychology, neurophysiology, imaging, genetics, epigenetics,
      and pharmacology of neurobehavioral comorbidities of epilepsy are absolutely
      instrumental for ensuring tangible progress in the field. Clinical research
      should focus more on new-onset epilepsy and put particular emphasis on
      longitudinal studies in large cohorts of patients and groups at risk, while
      translational research should primarily focus on the development of valid
      preclinical systems which would allow investigating the fundamental mechanism of
      epilepsy comorbidities. The final goal of the described research efforts would
      lie in producing an armamentarium of evidence-based diagnostic tools and
      therapeutic interventions which would at minimum mitigate and at maximum prevent
      or abolish neurobehavioral comorbidities of epilepsy and, thus, improve the
      quality of life of those patients with epilepsy who suffer from the said
      comorbidities. 

PMID- 24333576
TI  - Adipocyte-derived factors impair insulin signaling in differentiated human
      vascular smooth muscle cells via the upregulation of miR-143.
AB  - Cardiovascular complications are common in patients with type 2 diabetes.
      Adipokines have been implicated in the induction of proliferative and pro
      atherogenic alterations in human vascular smooth muscle cells (hVSMC). Other
      reports demonstrated the importance of the miRNA cluster miR-143/145 in the
      regulation of VSMC homeostasis and insulin sensitivity. Here we investigated
      whether the detrimental effects of adipokines on hVSMC function could be ascribed
      to alterations in miR-143/145 expression. The exposure of hVSMC to conditioned
      media (CM) from primary human subcutaneous adipocytes increased the expression of
      smooth muscle alpha-actin (SMA), and the miR-143/145 cluster, but markedly
      impaired the insulin-mediated phosphorylation of Akt and its substrate
      endothelial nitric oxide synthase (eNOS). Furthermore, CM promoted the
      phosphorylation of SMAD2 and p38, which have both been linked to miR-143/145
      induction. Accordingly, the induction of miR-143/145 as well as the inhibition of
      insulin-mediated Akt- and eNOS-phosphorylation was prevented when hVSMC were
      treated with pharmacological inhibitors for Alk-4/5/7 and p38 before the addition
      of CM. The transfection of hVSMC with precursor miR-143, but not with precursor
      miR-145, resulted in impaired insulin-mediated phosphorylation of Akt and eNOS.
      This inhibition of insulin signaling by CM and miR-143 is associated with a
      reduction in the expression of the oxysterol-binding protein-related protein 8
      (ORP8). Finally, the knock-down of ORP8 resulted in impaired insulin-mediated
      phosphorylation of Akt in hVSMC. Thus, the detrimental effects of adipocyte
      derived conditioned media on insulin action in primary hVSMC can be ascribed to
      the Alk- and p38-dependent induction of miR-143 and subsequent downregulation of
      ORP8. 

PMID- 24333578
TI  - MicroRNA-344 inhibits 3T3-L1 cell differentiation via targeting GSK3beta of
      Wnt/beta-catenin signaling pathway.
AB  - Differentiation of 3T3-L1 cells into adipocytes involves a highly orchestrated
      series of complex events in which microRNAs might play an essential role. In this
      study, we found that the overexpression of microRNA-344 (miR-344) inhibits 3T3-L1
      cell differentiation and decreases triglyceride accumulation after MDI
      stimulation. We demonstrated that miR-344 directly targets the 3' UTR of GSK3beta
      (Glycogen synthase kinase 3 beta). Knockdown of GSK3beta with siRNA results in
      inhibiting 3T3-L1 differentiation, while its overexpression restores the effect
      of miR-344. In addition, miR-344 elevates the level of active beta-catenin, which
      is the downstream effector of GSK3beta in the Wnt/beta-catenin signaling pathway.
      These data indicate that miR-344 inhibits adipocyte differentiation via targeting
      GSK3beta and subsequently activating the Wnt/beta-catenin signaling pathway. 

PMID- 24333579
TI  - Construction of carotenoid biosynthetic pathways using squalene synthase.
AB  - The first committed steps of steroid/hopanoid pathways involve squalene synthase
      (SQS). Here, we report the Escherichia coli production of diaponeurosporene and
      diapolycopene, yellow C30 carotenoid pigments, by expressing human SQS and
      Staphylococcus aureus dehydrosqualene (C30 carotenoid) desaturase (CrtN). We
      suggest that the carotenoid pigments are synthesized mainly via the desaturation
      of squalene rather than the direct synthesis of dehydrosqualene through the non
      reductive condensation of prenyl diphosphate precursors, indicating the possible
      existence of a "squalene route" and a "lycopersene route" for C30 and C40
      carotenoids, respectively. Additionally, this finding yields a new method of
      colorimetric screening for the cellular activity of squalene synthases, which are
      major targets for cholesterol-lowering drugs. 

PMID- 24333580
TI  - Synthesis and evaluation of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(2-(4
      substitutedpiperazin-1-yl)acetyl)piperazin-1-yl)quinoline-3-carboxylic acid
      derivatives as anti-tubercular and antibacterial agents.
AB  - A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4
      substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues were
      synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and screened for their
      in vitro anti-tubercular and antibacterial activity. Many of these compounds
      exhibited MIC values in the range 7.32-136.10 MUM against Mycobacterium
      tuberculosis H37Rv. Eight compounds were further subjected to cytotoxic studies.
      Furthermore, the title compounds were screened for antibacterial activity against
      Staphylococcus aureus ATCC 29213 (gram positive) and Escherichia coli ATCC 25922
      (gram negative) bacteria. Many of these compounds exhibited MIC values in the
      range 0.44-34.02 MUM. Compound 3f was found to be the most active with an MIC of
      0.44 and 0.8 MUM respectively against both the strains. In general, the
      antibacterial activity of title compounds was more prominent.

PMID- 24333581
TI  - Synthesis and antiproliferative action of a novel series of maprotiline
      analogues.
AB  - The synthesis of a diverse library of compounds structurally related to
      maprotiline, a norepinephrine reuptake transporter (NET) selective antidepressant
      which has recently been identified as a novel in vitro antiproliferative agent
      against Burkitt's lymphoma (BL) cell lines is reported. A series of 9,10-dihydro
      9,10-ethanoanthracenes were synthesised with modifications to the bridge of the
      dihydroethanoanthracene structure and with alterations to the basic side chain. A
      number of compounds were found to reduce cell viability to a greater extent than
      maprotiline in BL cell lines. In addition a related series of novel 9-substituted
      anthracene compounds were investigated as intermediates in the synthesis of 9,10
      dihydro-9,10-ethanoanthracenes. These compounds proved the most active from the
      screen and were found to exert a potent caspase-dependant apoptotic effect in the
      BL cell lines, while having minimal effect on the viability of peripheral blood
      mononuclear cells (PBMCs). Compounds also displayed activity in multi-drug
      resistant (MDR) cells.

PMID- 24333582
TI  - Epidermal tattoo potentiometric sodium sensors with wireless signal transduction
      for continuous non-invasive sweat monitoring.
AB  - This article describes the fabrication, characterization and application of an
      epidermal temporary-transfer tattoo-based potentiometric sensor, coupled with a
      miniaturized wearable wireless transceiver, for real-time monitoring of sodium in
      the human perspiration. Sodium excreted during perspiration is an excellent
      marker for electrolyte imbalance and provides valuable information regarding an
      individual's physical and mental wellbeing. The realization of the new skin-worn
      non-invasive tattoo-like sensing device has been realized by amalgamating several
      state-of-the-art thick film, laser printing, solid-state potentiometry, fluidics
      and wireless technologies. The resulting tattoo-based potentiometric sodium
      sensor displays a rapid near-Nernstian response with negligible carryover
      effects, and good resiliency against various mechanical deformations experienced
      by the human epidermis. On-body testing of the tattoo sensor coupled to a
      wireless transceiver during exercise activity demonstrated its ability to
      continuously monitor sweat sodium dynamics. The real-time sweat sodium
      concentration was transmitted wirelessly via a body-worn transceiver from the
      sodium tattoo sensor to a notebook while the subjects perspired on a stationary
      cycle. The favorable analytical performance along with the wearable nature of the
      wireless transceiver makes the new epidermal potentiometric sensing system
      attractive for continuous monitoring the sodium dynamics in human perspiration
      during diverse activities relevant to the healthcare, fitness, military,
      healthcare and skin-care domains. 

PMID- 24333583
TI  - Protective effect of aquacultured flounder fish-derived peptide against oxidative
      stress in zebrafish.
AB  - This study investigates the protective effect of aquacultured flounder fish
      derived peptide (AFFP) against 2,2-azobis-(2-amidinopropane) hydrochloride (AAPH)
      induced oxidative damage in a zebrafish model. Zebrafish embryos were evaluated
      for the protective effect by heartbeat rate, survival rate, ROS generation, lipid
      peroxidation, and cell death. In the results, the AAPH group showed a low
      survival rate, whereas the AFFP and AAPH co-treated group increased a survival
      rate. Also, AFFP dose-dependently reduced AAPH-induced intracellular ROS and
      lipid peroxidation, and decreased cell death in AAPH-induced zebrafish. These
      results revealed that AFFP could be used as a natural antioxidant, and that the
      zebrafish provides an alternative in vivo model to efficiently evaluate the
      antioxidative effects of peptides on fishes. 

PMID- 24333584
TI  - Single-cell mRNA transfection studies: delivery, kinetics and statistics by
      numbers.
AB  - In artificial gene delivery, messenger RNA (mRNA) is an attractive alternative to
      plasmid DNA (pDNA) since it does not require transfer into the cell nucleus. Here
      we show that, unlike for pDNA transfection, the delivery statistics and dynamics
      of mRNA-mediated expression are generic and predictable in terms of mathematical
      modeling. We measured the single-cell expression time-courses and levels of
      enhanced green fluorescent protein (eGFP) using time-lapse microscopy and flow
      cytometry (FC). The single-cell analysis provides direct access to the
      distribution of onset times, life times and expression rates of mRNA and eGFP. We
      introduce a two-step stochastic delivery model that reproduces the number
      distribution of successfully delivered and translated mRNA molecules and thereby
      the dose-response relation. Our results establish a statistical framework for
      mRNA transfection and as such should advance the development of RNA carriers and
      small interfering/micro RNA-based drugs. FROM THE CLINICAL EDITOR: This team of
      authors established a statistical framework for mRNA transfection by using a two
      step stochastic delivery model that reproduces the number distribution of
      successfully delivered and translated mRNA molecules and thereby their dose
      response relation. This study establishes a nice connection between theory and
      experimental planning and will aid the cellular delivery of mRNA molecules.

PMID- 24333586
TI  - Safety of the intravenous administration of neurotensin-polyplex nanoparticles in
      BALB/c mice.
AB  - Neurotensin (NTS)-polyplex is a gene nanocarrier that has potential nanomedicine
      based applications for the treatment of Parkinson's disease and cancers of cells
      expressing NTS receptor type 1. We assessed the acute inflammatory response to
      NTS-polyplex carrying a reporter gene in BALB/c mice. The intravenous injection
      of NTS-polyplex caused the specific expression of the reporter gene in
      gastrointestinal cells. Six hours after an intravenous injection of propidium
      iodide labeled-NTS-polyplex, fluorescent spots were located in the cells of the
      organs with a mononuclear phagocyte system, suggesting NTS-polyplex clearance. In
      contrast to lipopolysaccharide and carbon tetrachloride, NTS-polyplex did not
      increase the serum levels of tumor necrosis factor alpha, interleukin (IL)-1beta,
      IL-6, bilirubin, aspartate transaminase, and alanine transaminase. NTS-polyplex
      increased the levels of serum amyloid A and alkaline phosphatase, but these
      levels normalized after 24 h. Compared to carrageenan, the local injection of NTS
      polyplex did not produce inflammation. Our results support the safety of NTS
      polyplex. FROM THE CLINICAL EDITOR: This study focuses on the safety of
      neurotensin (NTS)-polyplex, a gene nanocarrier that has potential in the
      treatment of Parkinson's disease and cancers of cells expressing NTS receptor
      type 1. NTS polyplex demonstrates a better safety profile compared with
      carrageenan, lipopolysaccharide, and carbon tetrachloride in a murine model.

PMID- 24333585
TI  - Photodynamic therapy with decacationic [60]fullerene monoadducts: effect of a
      light absorbing electron-donor antenna and micellar formulation.
AB  - We report the synthesis and anticancer photodynamic properties of two new
      decacationic fullerene (LC14) and red light-harvesting antenna-fullerene
      conjugated monoadduct (LC15) derivatives. The antenna of LC15 was attached
      covalently to C60>with distance of only <3.0 A to facilitate ultrafast
      intramolecular photoinduced-electron-transfer (for type-I photochemistry) and
      photon absorption at longer wavelengths. Because LC15 was hydrophobic we compared
      formulation in Cremophor EL micelles with direct dilution from dimethylacetamide.
      LC14 produced more (1)O2 than LC15, while LC15 produced much more HO.than LC14 as
      measured by specific fluorescent probes. When delivered by DMA, LC14 killed more
      HeLa cells than LC15 when excited by UVA light, while LC15 killed more cells when
      excited by white light consistent with the antenna effect. However LC15 was more
      effective than LC14 when delivered by micelles regardless of the excitation
      light. Micellar delivery produced earlier apoptosis and damage to the endoplasmic
      reticulum as well as to lysosomes and mitochondria. FROM THE CLINICAL EDITOR:
      This team of authors report the synthesis and the photodynamic properties of two
      new derivatives for cancer treatment; one is a decacationic fullerene (LC14) and
      the other is a red light-harvesting antenna-fullerene conjugated monoadduct
      (LC15) utilizing a HeLa cell model.

PMID- 24333587
TI  - Efficient delivery of immunostimulatory DNA to mouse and human immune cells
      through the construction of polypod-like structured DNA.
AB  - Investigation of mouse macrophage-like RAW264.7 cells showed that the
      immunostimulatory activity of CpG DNA is increased by formation of polypod-like
      structured DNA (polypodna), an assembly consisting of three or more
      oligodeoxynucleotides. To apply CpG polypodna to immunotherapy, its activity was
      examined in murine dendritic DC2.4 cells, splenic macrophages, and bone marrow
      derived dendritic cells (BMDCs). In all cell types, increasing the pod number
      increased the cellular uptake of DNA and cytokine release. No significant release
      of cytokines was observed in macrophages lacking Toll-like receptor 9. Similar
      results were obtained after intradermal injection of polypodna. The polypodna
      preparations produced significantly higher amounts of interferon alpha in human
      peripheral blood mononuclear cells (PBMCs) compared with single-stranded DNA. The
      conditioned medium of hexapodna-treated human PBMCs effectively inhibited the
      activity of a hepatitis C virus subgenomic replicon reporter system. These
      results indicate that polypodna preparations are useful as an immunostimulator.
      FROM THE CLINICAL EDITOR: This study demonstrates the utility of polypoid-like
      structured DNA (polypodna) preparations as potent immunostimulators in a murine
      model.

PMID- 24333588
TI  - Nanoprobing of misfolding and interactions of amyloid beta 42 protein.
AB  - The assembly of amyloid beta (Abeta) proteins into nanostructures is currently
      considered a major pathway of Alzheimer's disease development, but the molecular
      mechanisms of this self-assembly process remains unclear. Recently, we showed
      that single-molecule AFM force spectroscopy (SMFS) is capable of probing the
      dynamics and interaction between Abeta40 peptides, and these studies allowed us
      to shed new light on transiently existing Abeta40 misfolding states. In this
      study, we applied the same SMFS approach to characterize the misfolding of
      Abeta42 peptide, the most toxic Abeta alloform. The quantitative analysis of SMFS
      data demonstrated that Abeta interaction leads to the formation of dimers with a
      lifetime in the range of a second. Interaction via C-terminal segments prevailed
      at pH 7, but interaction within the peptide center prevailed at acidic pH levels.
      The difference in the misfolding properties for Abeta40 and Abeta42 peptides and
      the mechanisms of amyloid nanoassembly are discussed. FROM THE CLINICAL EDITOR:
      Despite decades of intense research, Alzheimer's disease still remains incurable.
      This novel study focuses on the assembly of amyloid beta proteins into
      nanostructures, which is a key mechanism in Alzheimer's disease development.
      Single molecule atomic force spectroscopy is utilized to shed light on the
      molecular mechanisms of this self-assembly process.

PMID- 24333589
TI  - Preclinical development of siRNA therapeutics: towards the match between
      fundamental science and engineered systems.
AB  - The evolution of synthetic RNAi faces the paradox of interfering with the human
      biological environment. Due to the fact that all cell physiological processes can
      be target candidates, silencing a precise biological pathway could be challenging
      if target selectivity is not properly addressed. Molecular biology has provided
      scientific tools to suppress some of the most critical issues in gene therapy,
      while setting the standards for siRNA clinical application. However, the protein
      down-regulation through the mRNA silencing is intimately related to the sequence
      specific siRNA ability to interact accurately with the potential target.
      Moreover, its in vivo biological fate is highly dependent on the successful
      design of a vehicle able to overcome both extracellular and intracellular
      barriers. Anticipating a great deal of innovation, crucial to meet the challenges
      involved in the RNAi therapeutics, the present review intends to build up a
      synopsis on the delivery strategies currently developed. FROM THE CLINICAL
      EDITOR: This review discusses recent progress and pertinent limiting factors
      related to the use of siRNA-s as efficient protein-specific "silencing" agents,
      focusing on targeted delivery not only to cells of interest, but to the proper
      intracellular destination.

PMID- 24333590
TI  - Regulation on mechanical properties of collagen: enhanced bioactivities of
      metallofullerol.
AB  - Increased mechanical property of extracellular matrix (ECM) around tumor tissue
      is highly correlated to the progression of cancer, and now its efficient
      regulation is still a challenge. Here, we report that Gd@C82(OH)22-collagen
      composites greatly suppress the malignant progression of cancer cells in vitro,
      and the metallofullerol can efficiently reduce the mechanical property of
      collagen matrix. Further study indicates that Gd@C82(OH)22 can firmly bind to
      tropocollagen, facilitate the nuclei and microfibril formation. The interference
      to interactions among tropocollagens leads to decreased amount and disturbed
      structure of collagen fibers. C60(OH)24, the fullerol counterpart of
      Gd@C82(OH)22, is studied in parallel and their impacts on collagen are strikingly
      modest. The comparison data reveals that the enhanced bioactivity of Gd@C82(OH)22
      is highly related with its surface-structure. This study is the first attempt to
      apply nanomedicines to manipulate the biophysical property of collagen matrix,
      providing a new sight to target ECM in cancer therapy. FROM THE CLINICAL EDITOR:
      Increased presence of "harder" collagen in the extracellular matrix (ECM) around
      the tumor tissue highly correlates with cancer progression. In this paper, a
      metallofullerol-based approach is reported as an efficient nanotechnology
      approach in reducing the mechanical properties of the synthesized collagen,
      paving the way to the development of novel anti-cancer therapies.

PMID- 24333591
TI  - Liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide
      affect Abeta aggregation features and cross the blood-brain-barrier: implications
      for therapy of Alzheimer disease.
AB  - Targeting amyloid-beta peptide (Abeta) within the brain is a strategy actively
      sought for therapy of Alzheimer's disease (AD). We investigated the ability of
      liposomes bi-functionalized with phosphatidic acid and with a modified ApoE
      derived peptide (mApoE-PA-LIP) to affect Abeta aggregation/disaggregation
      features and to cross in vitro and in vivo the blood-brain barrier (BBB). Surface
      plasmon resonance showed that bi-functionalized liposomes strongly bind Abeta
      (kD=0.6 MUM), while Thioflavin-T and SDS-PAGE/WB assays show that liposomes
      inhibit peptide aggregation (70% inhibition after 72 h) and trigger the
      disaggregation of preformed aggregates (60% decrease after 120 h incubation).
      Moreover, experiments with dually radiolabelled LIP suggest that bi
      functionalization enhances the passage of radioactivity across the BBB either in
      vitro (permeability=2.5*10(-5) cm/min, 5-fold higher with respect to mono
      functionalized liposomes) or in vivo in healthy mice. Taken together, our results
      suggest that mApoE-PA-LIP are valuable nanodevices with a potential applicability
      in vivo for the treatment of AD. From the clinical editor: Bi-functionalized
      liposomes with phosphatidic acid and a modified ApoE-derived peptide were
      demonstrated to influence Abeta aggregation/disaggregation as a potential
      treatment in an Alzheimer's model. The liposomes were able to cross the blood
      brain barrier in vitro and in vivo. Similar liposomes may become clinically
      valuable nanodevices with a potential applicability for the treatment of
      Alzheimer's disease.

PMID- 24333592
TI  - Efficient and safe internalization of magnetic iron oxide nanoparticles: two
      fundamental requirements for biomedical applications.
AB  - We have performed a series of in vitro tests proposed for the reliable assessment
      of safety associated with nanoparticles-cell interaction. A thorough analysis of
      toxicity of three different coating iron oxide nanoparticles on HeLa cells has
      been carried out including, methyl thiazol tetrazolium bromide (MTT) and Trypan
      blue exclusion tests, cell morphology observation by optical and Scanning
      Electron Microscopy (SEM), study of cytoskeletal components, analysis of cell
      cycle and the presence of reactive oxygen species (ROS). We have quantified
      magnetic nanoparticle internalization, determined possible indirect cell damages
      and related it to the nanoparticle coating. The results confirm a very low
      toxicity of the analyzed iron oxide nanoparticles into HeLa cells by multiple
      assays and pave the way for a more successful cancer diagnostic and treatment
      without secondary effects. FROM THE CLINICAL EDITOR: In this paper, three
      different iron oxide nanoparticles are studied and compared from the standpoint
      of safety and toxicity in HeLa cells, demonstrating low toxicity for each
      preparation, and paving the way to potential future clinical applications.

PMID- 24333593
TI  - Multimodal nanoparticles that provide immunomodulation and intracellular drug
      delivery for infectious diseases.
AB  - Infectious diseases are a worldwide health concern. For some infections, a common
      feature is the intracellular residence of the pathogen and evasion of the host
      immune response. In the case of tuberculosis (TB), Mycobacterium tuberculosis
      evades clearance within macrophages through suppression of intracellular reactive
      oxygen and nitrogen species (ROS/RNS) and pro-inflammatory cytokines. We propose
      new nanoparticle designs for infectious diseases, functionalized with ligands
      able to modulate the cellular immune response and concurrently deliver drug. We
      have designed 1,3-beta-glucan functionalized chitosan shell, poly(lactide)co
      glycolide core nanoparticles to stimulate ROS/RNS, pro-inflammatory cytokine
      secretion, and delivery of rifampicin inside human alveolar like macrophages
      (ALM). Nanoparticles significantly enhanced ALM secretion of IL-12p70 (2.9-fold),
      TNF-alpha (16-fold) and INF-gamma (23-fold) compared to controls over 24h, and
      doubled ROS/RNS generation over 6h. Nanoparticles could deliver 4-fold greater
      rifampicin into ALM compared to rifampicin solution. These results provide proof
      of-concept of multimodal nanoparticles and support their further development.
      FROM THE CLINICAL EDITOR: In this paper, a new nanoparticle design is proposed to
      address hard to treat infectious diseases such as TB, through the use of
      nanoparticles functionalized with ligands that are able to concurrently modulate
      the cellular immune response and deliver a drug. The authors have designed 1,3
      beta-glucan functionalized chitosan shell - poly(lactide)co-glycolide core
      nanoparticles to stimulate reactive oxygen and nitrogen species production, pro
      inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar
      like macrophages.

PMID- 24333594
TI  - Silver nanoparticles alter proteoglycan expression in the promotion of tendon
      repair.
AB  - This study demonstrates a novel method of using silver nanoparticles for Achilles
      tendon injury healing. In vitro results indicated a stimulatory effect on cell
      proliferation and collagen synthesis with silver nanoparticles. Biomechanical
      test on the 42-day post operation Achilles tendon sample exhibited a significant
      improvement in tensile modulus when compared to the untreated group. Histology
      suggested that silver nanoparticles promoted cell alignment and proteoglycan
      synthesis. The collagen deposition was also improved. An alleviation of tumor
      necrosis factor alpha, and an increase in fibromodulin and proliferating cell
      nuclear antigen expression were seen in silver nanoparticles group by
      immunohistochemistry. This study further corroborates the finding of our previous
      study that silver nanoparticles help to restore the functionality of injured
      connective tissues. We believe that the anti-inflammatory nature of silver
      nanoparticles has an important role in accelerating the healing process and
      reducing scarring, leading to better functional outcome. From the clinical
      editor: Tendon healing after surgeries remains a slow and tedious process,
      typically requiring several weeks of recovery time and gradual introduction of
      physical therapy. There are no currently utilized methods that could promote
      tendon healing. In this study, silver nanoparticles are reported to facilitate
      Achilles tendon repair in a model system, through increased proteoglycan and
      collagen synthesis, paving the way to potential clinical applications in the
      future.

PMID- 24333595
TI  - Magnetic nanoparticle-based immunoassay for rapid detection of influenza
      infections by using an integrated microfluidic system.
AB  - Magnetic manganese ferrite (MnFe2O4) nanoparticles with approximately 100nm in
      diameter were used to improve the performance of an immunoassay for detecting
      influenza infections. The synthesized nanoparticles were tested for long-term
      storage to confirm the stability of their thermal decomposition process. Then, an
      integrated microfluidic system was developed to perform the diagnosis process
      automatically, including virus purification and detection. To apply these
      nanoparticles for influenza diagnosis, a micromixer was optimized to reduce the
      dead volume within the microfluidic chip. Furthermore, the mixing index of the
      micromixer could achieve as high as 97% in 2seconds. The optical signals showed
      that this nanoparticle-based immunoassay with dynamic mixing could successfully
      achieve a detection limit of influenza as low as 0.007 HAU. When compared with
      the 4.5-MUm magnetic beads, the optical signals of the MnFe2O4 nanoparticles were
      twice as sensitive. Furthermore, five clinical specimens were tested to verify
      the usability of the developed system. FROM THE CLINICAL EDITOR: In this study,
      magnetic manganese ferrite nanoparticles were used to improve the performance of
      a novel immunoassay for the rapid and efficient detection of influenza
      infections.

PMID- 24333596
TI  - Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and
      decreases invasion in MDA-MB-453 breast cancer cells.
AB  - Prolactin receptor (PRL-R) activation regulates cell differentiation,
      proliferation, cell survival and motility of breast cells. Prolactin (PRL) and
      PRL-R over-expression are strongly implicated in breast cancer, particularly
      contributing to tumor growth and invasion in the more aggressive estrogen
      receptor negative (ER-) disease. PRL-R antagonists have been suggested as
      potential therapeutic agents; however, mechanisms through which PRL-R antagonists
      exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for
      over 10% of the proteome, regulating critical cell processes such as
      proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R
      signaling regulates Zn metabolism in breast cells. Herein we determined effects
      of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER
      , PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post
      transcriptionally increased ZnT2 abundance and redistributed intracellular Zn
      pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration
      was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and
      decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated
      with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism
      in PRL-R over-expressing breast cancer cells may reduce invasion through the
      redistribution of intracellular Zn pools critical for cellular function. 

PMID- 24333597
TI  - Lineage specification in the early mouse embryo.
AB  - Before the mammalian embryo is ready to implant in the uterine wall, the single
      cell zygote must divide and differentiate into three distinct tissues;
      trophectoderm (prospective placenta), primitive endoderm (prospective yolk sac),
      and pluripotent epiblast cells which will form the embryo proper. In this review
      I will discuss our current understanding of how positional information, cell
      polarization, signaling pathways, and transcription factor networks converge to
      drive and regulate the progressive segregation of the first three cell types in
      the mouse embryo. 

PMID- 24333598
TI  - Endothelial connexin32 enhances angiogenesis by positively regulating tube
      formation and cell migration.
AB  - The gap junction proteins connexin32 (Cx32), Cx37, Cx40, and Cx43 are expressed
      in endothelial cells, and regulate vascular functions involving inflammation,
      vasculogenesis and vascular remodeling. Aberrant Cxs expression promotes the
      development of atherosclerosis which is modulated by angiogenesis; however the
      role played by endothelial Cxs in angiogenesis remains unclear. In this study, we
      determined the effects of endothelial Cxs, particularly Cx32, on angiogenesis.
      EA.hy926 cells that had been transfected to overexpress Cx32 significantly
      increased capillary length and the number on branches compared to Cx-transfectant
      cells over-expressing Cx37, Cx40, and Cx43 or mock-treated cells. Treatment via
      intracellular transfer of anti-Cx32 antibody suppressed tube formation of human
      umbilical vein endothelial cells (HUVECs) compared to controls. In vitro wound
      healing assays revealed that Cx32-transfectant cells significantly increased the
      repaired area while anti-Cx32 antibody-treated HUVECs reduced it. Ex vivo aorta
      ring assays and in vivo matrigel plaque assays showed that Cx32-deficient mice
      impaired both vascular sprouting from the aorta and cell migration into the
      implanted matrigel. Therefore endothelial Cx32 facilitates tube formation, wound
      healing, vascular sprouting, and cell migration. Our results suggest that
      endothelial Cx32 positively regulates angiogenesis by enhancing endothelial cell
      tube formation and cell migration. 

PMID- 24333600
TI  - Carbonic anhydrase induction in euryhaline crustaceans is rate-limited at the
      post-transcriptional level.
AB  - The transfer of euryhaline crustaceans from full-strength seawater to low
      salinity results in both a rapid up-regulation of carbonic anhydrase (CA; EC
      4.2.1.1) mRNA and a slow induction of CA activity. There is a delay of several
      days between the two processes, which is attributed to the time required to
      synthesize new enzyme. These delays may also be due to limitations in the
      cellular uptake of Zn, which is a required post-translational active site
      modification to CA. To investigate these processes, the euryhaline crabs,
      Callinectes sapidus and Carcinus maenas, were acclimated to salinities below
      their isosmotic points (22.5 and 25 ppt, respectively) for 7 days to activate the
      physiological and molecular mechanisms of osmoregulation. CA mRNA increased 90
      fold in C. sapidus and 2-fold in C. maenas within 6h; whereas it took 48 h for
      the initial increases in CA activity (120% and 31%), and 4 to 7 days for new
      acclimated levels (300% and 100%, respectively). Crabs were then transferred to
      lower salinities (10 and 15 ppt) to induce further CA activity and to determine
      if previous increases in CA mRNA reduced the time required for subsequent CA
      induction. Additionally, the expression of the Zn transporter ZIP1 was examined
      in C. sapidus at 35 and 22.5 ppt. In both species, prior CA mRNA elevation failed
      to accelerate the rate of CA induction. Levels of CA mRNA did not change in
      either crab following transfer from intermediate to low salinity. Taken together,
      these results show that the timecourse of CA induction at low salinity is not
      limited by the expression of CA mRNA, but by the synthesis of new enzyme from an
      existing pool of mRNA. No increases in ZIP1 expression occurred at low salinity,
      therefore these delays may be due to the limits of cellular Zn uptake.

PMID- 24333601
TI  - Smelling salt: calcium as an odourant for fathead minnows.
AB  - Calcium plays an essential role in olfactory sensory neuron function. Studies
      with fish have indicated that in addition to being involved in olfactory
      signalling, calcium is itself an odourant. In this study we used fathead minnows
      (Pimephales promelas) and employed two different techniques; electro
      olfactography (EOG), a neurophysiological technique that measures olfactory
      acuity at the olfactory epithelium, and a behavioural choice assay using a trough
      maze. The results demonstrate that calcium and a known odourant L-arginine are
      cross-adaptive, that calcium induces an EOG response in a concentration-dependent
      manner, and that calcium induces a strong avoidance behaviour. The behavioural
      avoidance was also demonstrated to be olfactory-dependent. Taken together, the
      results demonstrate that calcium is a potent odourant for fathead minnows. Being
      able to smell calcium may represent an ability to sense and avoid areas with
      significant changes in ionic strength, thereby avoiding physiological stress. 

PMID- 24333599
TI  - Structural and temporal requirements of Wnt/PCP protein Vangl2 function for
      convergence and extension movements and facial branchiomotor neuron migration in
      zebrafish.
AB  - Van gogh-like 2 (Vangl2), a core component of the Wnt/planar cell polarity (PCP)
      signaling pathway, is a four-pass transmembrane protein with N-terminal and C
      terminal domains located in the cytosol, and is structurally conserved from flies
      to mammals. In vertebrates, Vangl2 plays an essential role in convergence and
      extension (CE) movements during gastrulation and in facial branchiomotor (FBM)
      neuron migration in the hindbrain. However, the roles of specific Vangl2 domains,
      of membrane association, and of specific extracellular and intracellular motifs
      have not been examined, especially in the context of FBM neuron migration.
      Through heat shock-inducible expression of various Vangl2 transgenes, we found
      that membrane associated functions of the N-terminal and C-terminal domains of
      Vangl2 are involved in regulating FBM neuron migration. Importantly, through
      temperature shift experiments, we found that the critical period for Vangl2
      function coincides with the initial stages of FBM neuron migration out of
      rhombomere 4. Intriguingly, we have also uncovered a putative nuclear
      localization motif in the C-terminal domain that may play a role in regulating CE
      movements. 

PMID- 24333602
TI  - Risk index for predicting shunt in carotid endarterectomy.
AB  - BACKGROUND: To prevent ischemia during carotid endarterectomy, a routine or
      selective shunt can be set up in cases of insufficient cerebral perfusion during
      the carotid clamping. The aim of this study was to analyze predictive factors for
      shunting under locoregional anesthesia and to validate a risk index to predict
      shunt. METHODS: Using a prospective database, we studied carotid endarterectomy
      performed under locoregional anesthesia between January 1, 2003, and December 31,
      2010 (n=1,223). A shunt was used because of clinical intolerance of clamping in
      88 cases (group S, 7.2%). Clinical, comorbidities, demographics, and duplex scan
      data were used to compare group S to a control group (group C, n=1,135, 92.8%). A
      multivariable logistic regression was performed to identify predictors of shunt.
      Coefficients were assigned to each predictor to propose a predictive score.
      RESULTS: Patients in group S were significantly older than those in group C
      (75.6+/-7.8 years vs. 72.6+/-9.4 years, P<0.001). Other factors associated with a
      carotid shunt were female sex (odds ratio [OR]=2.41, 95% confidence interval
      [CI]: 1.54-3.78, P<0.001), systemic arterial hypertension (OR=2.478, 95% CI: 1.16
      4.46, P=0.016), occlusion of the contralateral carotid artery (OR=6.03, 95% CI:
      2.91-12.48, P<0.001), and 1 factor against the likelihood of a carotid shunt, a
      history of contralateral carotid surgery (OR=0.34, 95% CI: 0.12-0.93, P=0.037).
      The mean flow in the contralateral common carotid artery was 696.5+/-298.0 mL/sec
      in group S and 814.7+/-285.5 mL/sec in group C (P<0.001). Using those 6 items, we
      propose a prognostic score validated in our series and allowing to divided risk
      of intolerance of clamping into low-risk (<=6%), intermediate-risk (6.1%-15%),
      and high-risk (>15%) groups. CONCLUSIONS: We have established the first version
      of a score that predicts the need for a shunt by studying factors associated with
      intolerance to clamping. The relevance of this score, validated in our series,
      must be confirmed and adjusted by studies based on a larger sample size.

PMID- 24333603
TI  - The 100-year evolution of the isolated internal iliac artery aneurysm.
AB  - BACKGROUND: Isolated internal iliac artery aneurysms (IIIAA) are a rare form of
      aneurysm. The incidence increases with age, and the prevalence is higher in men.
      The clinical presentation can vary, and standard treatment protocols are not
      established. The first case of an IIIAA was described more than 100 years ago.
      The purpose of the study is to summarize the various clinical presentations and
      treatment options that have been reported in the literature in the past 100
      years. METHODS: Literature about IIIAA was reviewed using the electronic databank
      PubMed. All case reports and case series were analyzed, and we included our own
      data with 2 case reports. RESULTS: Over time, IIIAA diagnosis increasingly
      resulted from asymptomatic incidental findings on radiologic studies. Various
      clinical presentations included abdominal pain, back pain, rectal bleeding,
      hydronephrosis with renal failure, hematuria, and free rupture with shock.
      Rupture has a mortality rate of 53%. IIIAAs were more common on the left (61.8%
      left, 27.3% right, 10.9% bilateral). Treatments include open surgical repair and
      endovascular repair using a variety of methods. One article reported a hybrid
      method using both endovascular and open surgical technique. CONCLUSIONS: Since
      its first description 100 years ago, we have gained knowledge about the natural
      history of IIIAA. Multiple treatment options have been described, but long-term
      outcome needs further investigation.

PMID- 24333604
TI  - Influence of social and built environment features on children walking to school:
      an observational study.
AB  - OBJECTIVES: To estimate the proportion of children living within walking distance
      who walk to school in Toronto, Canada and identify built and social environmental
      correlates of walking. METHODS: Observational counts of school travel mode were
      done in 2011, at 118 elementary schools. Built environment data were obtained
      from municipal sources and school field audits and mapped onto school attendance
      boundaries. The influence of social and built environmental features on walking
      counts was analyzed using negative binomial regression. RESULTS: The mean
      proportion observed walking was 67% (standard deviation=14.0). Child population
      (incidence rate ratio (IRR) 1.36), pedestrian crossover (IRR 1.32), traffic light
      (IRR 1.19), and intersection densities (IRR 1.03), school crossing guard (IRR
      1.14) and primary language other than English (IRR 1.20) were positively
      correlated with walking. Crossing guard presence reduced the influence of other
      features on walking. CONCLUSIONS: This is the first large observational study
      examining school travel mode and the environment. Walking proportions were higher
      than those previously reported in Toronto, with large variability. Associations
      between population density and several roadway design features and walking were
      confirmed. School crossing guards may override the influence of roadway features
      on walking. Results have important implications for policies regarding walking
      promotion.

PMID- 24333605
TI  - Prevalence and correlates of victimization and weapon carrying among military-
      and nonmilitary-connected youth in Southern California.
AB  - OBJECTIVES: The present analysis sought to explore the normative rates and
      correlates of school victimization and weapon carrying among military-connected
      and nonmilitary-connected youth in public schools in Southern California.
      METHODS: Data are from a sub-sample of the 2011 California Healthy Kids Survey
      (N=14,512). Items to assess victimization and weapon carrying were separated into
      three categories: physical acts (e.g., being pushed or shoved), nonphysical acts
      (e.g., having rumors spread about them) and weapon carrying. RESULTS: The
      bivariate results indicate that youth with a military-connected parent had higher
      rates of physical victimization (56.8%), nonphysical victimization (68.1%), and
      weapon carrying (14.4%) compared to those with siblings serving (55.2%, 65.2%,
      and 11.4%, respectively) and nonmilitary-connected (50.3%, 61.6%, and 8.9%,
      respectively) youth. Having a parent in the military increased the odds of weapon
      carrying by 29% (Odds Ratio=1.29, 95% confidence interval=1.02-1.65). Changing
      schools and a larger number of family member deployments in the past 10years were
      associated with significant increases in the likelihood of victimization and
      weapon carrying. CONCLUSIONS: The results of this analysis warrant a focus on
      school supports for youth experiencing parental military service, multiple
      relocations and deployments of a family member.

PMID- 24333606
TI  - Symptoms of depression are longitudinally associated with sedentary behaviors
      among young men but not among young women.
AB  - OBJECTIVE: A habitual sedentary lifestyle is associated with adverse health
      outcomes; however, the predictors of sedentary behaviors have not been
      sufficiently explored to inform the development and delivery of effective
      interventions to reduce sedentary behaviors. This study examined whether reports
      of symptoms of depression could predict weekly time spent in sedentary behaviors
      (i.e., television watching, computer use) 4years later. METHOD: Self-reported
      symptoms of depression were assessed at age 20years (2007-08), and television
      watching time and computer use were assessed at age 24years (2011-12) in 761
      adults (45% men) participating in the Nicotine Dependence in Teens study. Data
      were analyzed using linear regression analysis, with separate models for men and
      women. RESULTS: After controlling for past sedentary behavior, symptoms of
      depression at age 20years predicted more computer use 4years later in men
      (R(2)=.21, beta=.13, p<.05), but not in women. Symptoms of depression did not
      predict television watching. CONCLUSIONS: Results highlight the need to
      distinguish between types of sedentary behaviors as their predictors may differ.
      Further, they provide support for the hypothesis that psychological factors, in
      this case symptoms of depression, may relate to select sedentary behaviors in
      young men.

PMID- 24333607
TI  - Metabolic engineering of fatty acyl-ACP reductase-dependent pathway to improve
      fatty alcohol production in Escherichia coli.
AB  - Fatty alcohols are important components of surfactants and cosmetic products. The
      production of fatty alcohols from sustainable resources using microbial
      fermentation could reduce dependence on fossil fuels and greenhouse gas emission.
      However, the industrialization of this process has been hampered by the current
      low yield and productivity of this synthetic pathway. As a result of metabolic
      engineering strategies, an Escherichia coli mutant containing Synechococcus
      elongatus fatty acyl-ACP reductase showed improved yield and productivity.
      Proteomics analysis and in vitro enzymatic assays showed that endogenous E. coli
      AdhP is a major contributor to the reduction of fatty aldehydes to fatty
      alcohols. Both in vitro and in vivo results clearly demonstrated that the
      activity and expression level of fatty acyl-CoA/ACP reductase is the rate
      limiting step in the current protocol. In 2.5-L fed-batch fermentation with
      glycerol as the only carbon source, the most productive E. coli mutant produced
      0.75 g/L fatty alcohols (0.02 g fatty alcohol/g glycerol) with a productivity of
      up to 0.06 g/L/h. This investigation establishes a promising synthetic pathway
      for industrial microbial production of fatty alcohols.

PMID- 24333608
TI  - Three-stage continuous culture system with a self-generated anaerobia to study
      the regionalized metabolism of the human gut microbiota.
AB  - The technical and ethical difficulties in studying the gut microbiota in vivo
      warrant the development and improvement of in vitro systems able to simulate and
      control the physicochemical factors of the gut biology. Moreover, the functional
      regionalization of this organ implies a model simulating these differences. Here
      we propose an improved and alternative three-stage continuous bioreactor called
      3S-ECSIM (three-stage Environmental Control System for Intestinal Microbiota) to
      study the human large intestine. Its main feature compared with other in vitro
      systems is the anaerobic atmosphere originating directly from the microbiota
      metabolism, leading to different gas ratios of CO2 and H2 in each compartment.
      Analyses of the metabolic and microbiological profiles (LC-MS and a phylogenetic
      microarray) show different profiles together with a maintenance of this
      differentiation between the three compartments, simulating respectively a
      proximal, a transversal and a distal colon. Moreover, the last reactor presents a
      high similarity with the initial fecal sample, at the microbiological diversity
      level. Based on our results, this in-vitro process improvement is a valuable
      alternative tool to dynamically study the structure and metabolism of gut
      microbiota, and its response to nutrients, prebiotics, probiotics, drugs or
      xenobiotics. 

PMID- 24333609
TI  - Synthesis and antiproliferative activity of new derivatives containing the
      polycyclic system 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3',4':2,3]azepino[4,5
      f]azocine.
AB  - The reaction under reflux between 1-phenyl-3-R-5-methylaminopyrazoles and 2,5
      hexanedione lead to 5,7:7,13-dimethanopyrazolo[3,4
      b]pyrazolo[3',4':2,3]azepino[4,5-f]azocine derivatives 3b-g. These unusual
      molecules show the structural complexity of many biologically active natural
      products and are endowed with the chemical diversity that is required in drug
      discovery. The compounds 3b,e were reduced by hydrogen in the presence of
      Palladium on activated charcoal to give the dihydro derivatives 5b,e. Compounds
      3b-f and 5b,e were selected by the NCI to evaluate their in vitro
      antiproliferative activity against 60 human cell lines derived from nine
      clinically isolated cancer types (leukaemia, lung, colon, melanoma, renal,
      ovarian, brain, breast, and prostate). The most active compound of this series,
      caused a block in G0-G1 phase of cell cycle. Analysis of pRb expression showed
      that this compound favours pRb dephosphorylation. 

PMID- 24333610
TI  - Synthesis and biological evaluation of fatty acids conjugates bearing
      cyclopentadienyl-donors incorporated [(99m)Tc/Re(CO)3]+ for myocardical imaging.
AB  - Four (99m)Tc-labeled fatty acid analogs, 1b, 2b, 3b, 4b were synthesized by a
      double ligand transfer reaction and theirs potential were investigated. The
      radiochemical yield of the radiotracers was from 11.7% to 30.3% (no decay
      corrected). Those compounds were found to be chemically stable when incubated in
      SD rat serum for 3 h at 37  degrees C. The biodistribution studies in mice showed
      that high radioactivity accumulated of Tc-99m complexes were observed, followed
      by moderate clearance from the heart. The maximum heart/blood ratio was 5.7 at 15
      min postinjection of 1b. Metabolite analysis showed 1b was not metabolized by
      beta-oxidation in the heart. These results suggest that 1b may be a promising
      radiotracer for evaluation of myocardial viability. 

PMID- 24333611
TI  - Synthesis, characterization and antibacterial activity of polyaniline/Pt-Pd
      nanocomposite.
AB  - Pt colloid and Pt-Pd colloid, pristine polyaniline, polyaniline/Pt nanocomposite
      and polyaniline/Pt-Pd nanocomposite were synthesized by simple chemical method.
      They were characterized by UV-Vis, FT-IR, XRD, TGA, SEM, HR-SEM and HR-TEM with
      EDAX techniques. The results proved that there is a strong interaction between
      metal nanoparticles (Pt-Pd) and polyaniline chains. This interaction creates
      changes in the backbone chain of polyaniline/Pt-Pd nanocomposite when compared to
      pristine polyaniline. The synthesized materials were evaluated for antibacterial
      activity, minimal inhibitory concentration and minimal bactericidal
      concentration. The results indicated that the nanocomposites exhibited improved
      antibacterial activity when compared to pristine polyaniline and individual metal
      colloids. This is the first report on the chemical synthesis of polyaniline/Pt-Pd
      nanocomposite, which exhibits antibacterial activity at micro molar concentration
      levels. 

PMID- 24333612
TI  - Design, synthesis and investigation on the structure-activity relationships of N
      substituted 2-aminothiazole derivatives as antitubercular agents.
AB  - Tuberculosis (TB) is one of the deadliest infectious diseases of all times, and
      its recent resurgence is a supreme matter of concern. Co-infection with HIV and,
      in particular, the continuous isolation of new resistant strains, makes the
      discovery of novel anti-TB agents a strategic priority. The research of novel
      agents should be driven by the accessibility of the synthetic procedure and, in
      particular, by the lack of cross-resistance with the drugs already marketed.
      Moreover, in order to shorten the duration of the therapy, and therefore decrease
      the rate of resistance, these molecules should be active also against the
      nonreplicating persistent form (NRP-TB) of the infection. The availability of an
      in-house small library of compounds prompted us to investigate their anti-TB
      activity. Two compounds, embodying a 2-aminothiazole scaffold, were found to
      possess a certain inhibitory activity toward Mycobacterium tuberculosis H37Rv,
      and therefore a medicinal chemistry campaign was initiated in order to increase
      the activity of the hit compounds and, especially, construct a plausible body of
      structure-activity relationships. The potency of the hit compound was
      successfully improved, and, much more importantly, some of the molecules
      synthesized were found to be active toward the persistent phenotype, and, also,
      toward a panel of resistant strains. These findings encourage further
      investigations around this interesting antitubercular chemotype. 

PMID- 24333613
TI  - Design, synthesis and anti-inflammatory evaluation of novel 5-benzylidene-3,4
      dihalo-furan-2-one derivatives.
AB  - Rosiglitazone has shown promising anti-inflammation effect. To develop preferable
      anti-inflammatory agents, twenty-two rosiglitazone analogs were synthesized and
      their anti-inflammatory activity was evaluated. Among these compounds, 6i and 6k
      displayed excellent inhibitory activities on the production of inflammatory
      mediators, including nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6). Furthermore, 6i and 6k showed suppression effects on
      the nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinase
      (MAPK) pathways, and this suppression effects could be partially reversed by
      GW9662, which is a peroxisome proliferator-activated receptor gamma (PPARgamma)
      antagonist. Additionally, our docking results exhibited the well combination of
      6i and 6k to PPARgamma. So the anti-inflammation activity of 6i and 6k was due at
      least in part, to their interaction with PPARgamma. 

PMID- 24333614
TI  - Detection of Janus Kinase 2 gene single point mutation in real samples with
      electrochemical DNA biosensor.
AB  - Janus Kinase 2 (JAK2) gene single point mutations, which have been reported to be
      associated with myeloproliferative disorders, are usually detected through
      conventional methods such as melting curve assays, allele-specific and
      quantitative Polymerase Chain Reactions (PCRs). Herein, an electrochemical
      biosensor for the detection of a Guanine (G) to Thymine (T) transversion at
      nucleotide position 1849 of the JAK2 gene was reported. Due to clinical
      importance of this mutation, easy and sensitive tests are needed to be developed.
      Our aim was to design a biosensor system that is capable of detecting the
      mutation within less than 1h with high sensitivity. For these purposes, an
      electrochemical sensing system was developed based on detecting hybridization.
      Hybridization between probe and its target and discrimination of single point
      mutation was investigated by monitoring guanine oxidation signals observed at
      +1.0 V with Differential Pulse Voltammetry (DPV) by using synthetic
      oligonucleotides and Polymerase Chain Reaction (PCR) amplicons. Hybridization
      between probe and PCR amplicons was also determined with Electrochemical
      Impedance Spectroscopy (EIS). We successfully detect hybridization first in
      synthetic samples, and ultimately in real samples involving blood samples from
      patients as well as additional healthy controls. The limit of detection (S/N=3)
      was calculated as 44 pmol of target sequence in a 40-MUl reaction volume in real
      samples.

PMID- 24333615
TI  - Standardisation of test requesting and reporting for the electronic health
      record.
AB  - This paper is a review of the standardisation required to achieve
      interoperability for pathology test requesting and reporting. Interoperability is
      the ability of two parties, either human or machine, to exchange data or
      information in a manner that preserves shared meaning. This is needed to make
      healthcare safer, more efficient and more effective. Interoperability requires
      standardisation around: transmission of data; identification policies;
      information structures; common terminology; common understanding; and behavioural
      agreement. It is dependent on consensus. Each of these aspects is considered from
      the perspective of pathology requesting and reporting concluding that while much
      has been done, much remains to be done.

PMID- 24333616
TI  - A standing dilemma: autonomic failure preceding Hodgkin's lymphoma.

PMID- 24333617
TI  - TB determined: tuberculous osteomyelitis.

PMID- 24333618
TI  - Warfarin, calciphylaxis, atrial fibrillation, and patients on dialysis: outlier
      subsets and practice guidelines.

PMID- 24333619
TI  - Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair
      deficiency in Lynch syndrome-like tumors.
AB  - Lynch syndrome is caused by germline mutations in the mismatch repair (MMR)
      genes. Tumors are characterized by microsatellite instability (MSI). However, a
      considerable number of MSI-positive tumors have no known molecular mechanism of
      development. By using Sanger and ion semiconductor sequencing, 25 MSI-positive
      tumors were screened for somatic mutations and loss of heterozygosity in mutL
      homolog 1 (MLH1) and mutS homolog 2 (MSH2). In 13 of 25 tumors (8 MLH1-deficient
      and 5 MSH2-deficient tumors), we identified 2 somatic mutations in these genes.
      We conclude that 2 acquired events explain the MMR-deficiency in more than 50% of
      the MMR-deficient tumors without causal germline mutations or promoter
      methylation. 

PMID- 24333620
TI  - Transient oxygen-glucose deprivation sensitizes brain capillary endothelial cells
      to rtPA at 4h of reoxygenation.
AB  - Thrombolysis treatment of acute ischemic stroke is limited by the pro-edematous
      and hemorrhagic effects exerted by reperfusion, which disrupts the blood-brain
      barrier (BBB) capillary endothelium in the infarct core. Most studies of the
      ischemic BBB overlook the complexity of the penumbral area, where the affected
      brain cells are still viable following deprivation. Our present objective was to
      examine in vitro the kinetic impact of reoxygenation on the integrity of ischemic
      BBB cells after oxygen-glucose deprivation. Through the use of a co-culture of
      brain capillary endothelial cells and glial cells, we first showed that the
      transendothelial permeability increase induced by deprivation can occur with both
      preserved cell viability and interendothelial tight junction network. The subtle
      and heterogeneous alteration of the tight junctions was observable only through
      electron microscopy. A complete permeability recovery was then found after
      reoxygenation, when Vimentin and Actin networks were reordered. However, still
      sparse ultrastructural alterations of tight junctions suggested an acquired
      vulnerability. Endothelial cells were then exposed to recombinant tissue-type
      plasminogen activator (rtPA) to define a temporal profile for the toxic effect of
      this thrombolytic on transendothelial permeability. Interestingly, the
      reoxygenated BBB broke down with aggravated tight junction disruption when
      exposed to rtPA only at 4h after reoxygenation. Moreover, this breakdown was
      enhanced by 50% when ischemic glial cells were present during the first hours of
      reoxygenation. Our results suggest that post-stroke reoxygenation enables
      retrieval of the barrier function of brain capillary endothelium when in a non
      necrotic environment, but may sensitize it to rtPA at the 4-hour time point, when
      both endothelial breakdown mechanisms and glial secretions could be identified
      and targeted in a therapeutical perspective. 

PMID- 24333621
TI  - A bioengineered array of 3D microvessels for vascular permeability assay.
AB  - Blood vessels exhibit highly regulated barrier function allowing selective
      passage of macromolecules. Abnormal vascular permeability caused by disorder in
      barrier function is often associated with various pathological states such as
      tumor progression or pulmonary fibrosis. There are no realistic in vitro models
      for measuring vascular permeability as most models are limited to mimicking
      anatomical structural properties of in vivo vessel barriers. This paper presents
      a reliable microfluidic-based chip for measuring permeability by engineering
      tubular perfusable microvessels. This platform is compatible with high
      resolution, live-cell time-lapse imaging and high throughput permeability
      measurements. The microvessels were formed by natural angiogenic process and thus
      exhibit reliable barrier properties with permeability coefficient of 1.55*10(
      6)cm/s (for 70kDa FITC-dextran). The bioengineered microvessels showed properties
      similar to in vivo vessels in terms of cell-cell junction expression (ZO-1,
      Claudin-5 and VE-cadherin) and response to agonists such as histamine and TNF
      alpha. We showed that hyperpermeability of the tumor microvessel could be
      normalized with anti-VEGF (bevacizumab) treatment, consistent with the mechanism
      of action for bevacizumab. The method developed here provides a relatively
      simple, robust technique for assessing drug effects on permeability of
      microvessels with a number of potential applications in fundamental vascular
      biology as well as drug screening. 

PMID- 24333622
TI  - Phylogenetic affinity of tree shrews to Glires is attributed to fast evolution
      rate.
AB  - Previous phylogenetic analyses have led to incongruent evolutionary relationships
      between tree shrews and other suborders of Euarchontoglires. What caused the
      incongruence remains elusive. In this study, we identified 6845 orthologous genes
      between seventeen placental mammals. Tree shrews and Primates were monophyletic
      in the phylogenetic trees derived from the first or/and second codon positions
      whereas tree shrews and Glires formed a monophyly in the trees derived from the
      third or all codon positions. The same topology was obtained in the phylogeny
      inference using the slowly and fast evolving genes, respectively. This
      incongruence was likely attributed to the fast substitution rate in tree shrews
      and Glires. Notably, sequence GC content only was not informative to resolve the
      controversial phylogenetic relationships between tree shrews, Glires, and
      Primates. Finally, estimation in the confidence of the tree selection strongly
      supported the phylogenetic affiliation of tree shrews to Primates as a monophyly.

PMID- 24333623
TI  - Mixotrophic growth and biochemical analysis of Chlorella vulgaris cultivated with
      diluted monosodium glutamate wastewater.
AB  - Monosodium glutamate wastewater (MSGW) is a potential medium for microbial
      cultivation because of containing abundant organic nutrient. This paper seeks to
      evaluate the feasibility of growing Chlorella vulgaris with MSGW and assess the
      influence of MSGW concentration on the biomass productivity and biochemical
      compositions. The MSGW diluted in different concentrations was prepared for
      microalga cultivation. C. vulgaris growth was greatly promoted with MSGW compared
      with the inorganic BG11 medium. C. vulgaris obtained the maximum biomass
      concentration (1.02 g/L) and biomass productivity (61.47 mg/Ld) with 100-time
      diluted MSGW. The harvested biomass was rich in protein (36.01-50.64%) and low in
      lipid (13.47-25.4%) and carbohydrate (8.94-20.1%). The protein nutritional
      quality and unsaturated fatty acids content of algal increased significantly with
      diluted MSGW. These results indicated that the MSGW is a feasible alternative for
      mass cultivation of C. vulgaris.

PMID- 24333624
TI  - Inhibition of biomass activity in the via nitrite nitrogen removal processes by
      veterinary pharmaceuticals.
AB  - The inhibitory effect of two veterinary pharmaceuticals was studied for different
      types of biomass involved in via nitrite nitrogen removal processes. Batch tests
      were conducted to determine the inhibition level of acetaminophen (PAR) and
      doxycycline (DOX) on the activity of short-cut nitrifying, denitrifying and
      anoxic ammonium oxidation (anammox) biomass and phosphorus accumulating organisms
      (PAOs). All biomass types were affected by PAR and DOX, with anammox being the
      most sensitive bacteria. DOX inhibited more the biomass treating high strength
      nitrogenous effluents (HSNE) than low strength nitrogenous effluents (LSNE). The
      phosphorus uptake inhibition under anoxic conditions was lower than 25% in the
      presence of PAR up to 400 mg L(-1). The same DOX concentration inhibited anoxic
      phosphorus uptake more than 65% for biomass treating LSNE and HSNE. Heterotrophic
      denitrifying bacteria seem to be more robust at high DOX and PAR concentrations
      than anammox. Both veterinary products inactivated ammonium oxidizing,
      Accumulibacter phosphatis and denitrifying bacteria.

PMID- 24333625
TI  - Nutrient removal from agricultural drainage water using algal turf scrubbers and
      solar power.
AB  - The objectives of this study were to determine nutrient removal rates and costs
      using solar-powered algal turf scrubber (ATS) raceways and water from an
      agricultural drainage ditch. Algal productivity using daytime-only flow was 3
      lower compared to productivity using continuous flow. Results from this and other
      studies suggest a non-linear relationship between flow rate and nitrogen removal
      rates. Nitrogen (N) and phosphorus (P) removal rates averaged 125 mg N, 25 mg P
      m(-2) d(-1) at the highest flow rates. Nutrient removal rates were equivalent to
      310 kg N and 33 kg P ha(-1) over a 7 month season. Projected nutrient removal
      costs ($90-$110 kg(-1) N or $830-$1050 kg(-1) P) are >10-fold higher than
      previous estimates for ATS units used to treat manure effluents.

PMID- 24333626
TI  - Preparation and characteristics of bacterial polymer using pre-treated sludge
      from swine wastewater treatment plant.
AB  - Sterilization, alkaline-thermal, and acid-thermal treatments were applied to
      different suspended sludge solids (SSS) concentrations and the pre-treated sludge
      was used as raw material for bioflocculant-producing bacteria R3 to produce
      bioflocculant. After 60 h of fermentation, three forms of bioflocculant (broth,
      capsular, and slime) were extracted, and maximum broth bioflocculant of 2.9 and
      4.1 g L(-1) were produced in sterilized and alkaline-thermal treated sludge as
      compared to that of 1.8 g L(-1) in acid-thermal treated sludge. Higher
      bioflocculant quantity was produced in SS of 15, 25, and 35 g L(-1) compared to
      that produced in SS of 45, 55, and 65 g L(-1). Bioflocculant combined with 0.5 g
      Ca(2+) in 1.0 L kaolin suspension acted as conditioning agent, and maximum
      flocculating activity of 94.5% and 92.8% was achieved using broth and slime
      bioflocculant, respectively. The results demonstrated that wastewater sludge
      could be used as sources to prepare bioflocculants.

PMID- 24333627
TI  - Hybrid scaffold composed of hydrogel/3D-framework and its application as a
      dopamine delivery system.
AB  - Cell-based drug delivery systems (DDSs) have been increasingly exploited because
      cells can be utilized as a continuous drug delivering system to produce
      therapeutic molecules over a more extended period compared to the simple drug
      carriers. Although hydrogels have many advantages for this application, their
      mechanical properties are generally not desirable to structurally protect
      implanted cells. Here, we present a three-dimensional (3D) hybrid scaffold with a
      combination of a 3D framework and a hydrogel to enhance the mechanical properties
      without chemically altering the transport properties of the hydrogel. Based on
      the 3D Ormocomp scaffold (framework) fabricated by projection-based
      microstereolithography with defined parameters, we developed a 3D hybrid scaffold
      by injection of the mixture of cells and the alginate gel into the internal space
      of the framework. This hybrid scaffold showed the improved mechanical strength
      and the framework in the scaffold played the role of an adhesion site for the
      encapsulated cells during the culture period. Additionally, we confirmed its
      protection of exogenous human cells from acute immune rejection in a mouse model.
      Eventually, we demonstrated the feasibility of applying this hybrid scaffold to
      the treatment of Parkinson's disease as a cell-based DDS. Dopamine released from
      the 3D hybrid scaffolds encapsulating dopamine-secreting cells for 8weeks
      suggested its clinical applicability. Further study on its long-term efficacy is
      necessary for the clinical applicability of this 3D hybrid scaffold for the
      treatment of Parkinson's disease. 

PMID- 24333628
TI  - Oligomeric bile acid-mediated oral delivery of low molecular weight heparin.
AB  - Intestinal transporters are limited to the transport of small molecular
      substrates. Here, we describe the development of apical sodium-dependent bile
      acid transporter (ASBT)-targeted high-affinity oligomeric bile acid substrates
      that mediate the transmembrane transport of low molecular weight heparin (LMWH).
      Several oligomers of deoxycholic acid (oligoDOCA) were synthesized to investigate
      the substrate specificity of ASBT. To see the binding of oligoDOCA on the
      substrate-binding pocket of ASBT, molecular docking was used and the dissociation
      rate constants (KD) were measured using surface plasmon resonance. The KD for
      tetrameric DOCA (tetraDOCA) was 50-fold lower than that for monomeric DOCA,
      because tetraDOCA interacted with several hydrophobic grooves in the substrate
      binding pocket of ASBT. The synthesized oligoDOCA compounds were subsequently
      chemically conjugated to macromolecular LMWH. In vitro, tetraDOCA-conjugated LMWH
      (LHe-tetraD) had highest selectivity for ASBT during its transport. Orally
      administered LHe-tetraD showed remarkable systemic anticoagulation activity and
      high oral bioavailability of 33.5+/-3.2% and 19.9+/-2.5% in rats and monkeys,
      respectively. Notably, LHe-tetraD successfully prevented thrombosis in a rat
      model of deep vein thrombosis. These results represent a major advancement in
      ASBT-mediated LMWH delivery and may facilitate administration of many important
      therapeutic macromolecules through a non-invasive oral route. 

PMID- 24333629
TI  - Orexin A and B in vitro modify orexins receptors expression and gonadotropins
      secretion of anterior pituitary cells of proestrous rats.
AB  - AIM: Orexin A and orexin B (hypocretins) are neuropeptides synthesized mainly by
      neurons located in the lateral hypothalamus and projections throughout the brain.
      They are agonists at both the orexin 1 and orexin 2G protein-coupled receptors.
      They have been related to arousal, sleep and feeding, autonomic and
      neuroendocrine functions. Their role in the brain control of gonadotropins
      secretion was postulated in rodents and humans. Previously, we demonstrated the
      participation of the orexinergic system in attaining successful reproduction in
      in vivo studies. METHODS: We studied in vitro the effects of both neuropeptides,
      in the presence or absence of selective antagonists, on the mRNA expression of
      orexin 1 and orexin 2 receptors in anterior pituitary cells of proestrous rats,
      as well as the direct effects on FSH and LH secretion. RESULTS: Both orexin A and
      orexin B increased FSH and LH secretion; these effects were suppressed by the
      orexin 1 receptor blocking agent SB-334867 and the orexin 2 receptor antagonists
      JNJ-10397049. Orexin A and orexin B decreased OX1 receptor mRNA expression and
      this effect was modified only when both blocking agents were present. Neither
      orexin A nor the blocking drugs by themselves modified OX2 receptor mRNA
      expression. Orexin B treatment increased the mRNA expression of OX2 receptor. The
      effect was abolished only by the OX2 receptor antagonist. CONCLUSION: In an in
      vitro model, we demonstrated a direct effect of orexins on gonadotropins release
      and orexins receptors expression, underlining the hypothesis that orexins
      participate in the brain control of pituitary functions.

PMID- 24333630
TI  - Des-aspartate-angiotensin I attenuates ICAM-1 formation in hydrogen peroxide
      treated L6 skeletal muscle cells and soleus muscle of mice subjected to eccentric
      exercise.
AB  - L6 skeletal muscle cells overexpressed ICAM-1 when treated with H2O2. Maximum
      effect was observed at 200 MUM H2O2. Des-aspartate-angiotensin I (DAA-I)
      concentration-dependently attenuated the overexpression. Maximum attenuation
      occurred at 10(-10) M DAA-I. H2O2 activated NFkappaB and its translocation into
      the nucleus of L6 muscle cells suggesting that NFkappaB mediates the H2O2-induced
      overexpression of ICAM-1. DAA-I inhibited the activation and translocation of
      NFkappaB. H2O2 is a major oxidant formed during skeletal muscle contraction and
      is implicated in oxidative stress and skeletal muscle damage in excessive
      unaccustomed exercise. The data show that DAA-I has antioxidant action, and its
      action was further investigated in the soleus muscle of mice subjected to 240 min
      of eccentric exercise on a rodent treadmill. The eccentric exercise induced
      superoxide formation and overexpression of ICAM-1 in the soleus muscle of the
      mice at 3 days post exercise. DAA-I (0.2 nmole/kg/day) administered orally on day
      1 (pre-exercise) and 2 days post-exercise attenuated both the ROS formation and
      ICAM-1 overexpression. Earlier studies show that DAA-I acts as an agonist on the
      angiotensin AT1 receptor and elicits responses opposing those of angiotensin II.
      The present and earlier findings support the recent suggestion that angiotensin
      II is involved in skeletal muscle damage, and curtailment of its actions via ACE
      inhibitors and losartan protects and improves skeletal muscle damage. These
      findings open up new avenues for treatment and management of skeletal muscle
      damage via the interventions of the renin angiotensin system.

PMID- 24333631
TI  - Validity of intraoperative diagnosis at laparoscopic surgery for ovarian tumors.
AB  - STUDY OBJECTIVE: To evaluate the accuracy and usefulness of intraoperative
      diagnosis of ovarian tumor during laparoscopic surgery. DESIGN: Retrospective
      cohort study (Canadian Task Force classification II-3). SETTING: Tertiary care
      university hospital. PATIENTS: We reviewed the cases of 262 patients who
      underwent laparoscopic surgery at our institution between January 2005 and
      December 2011 in whom a benign ovarian tumor was diagnosed intraoperatively.
      INTERVENTIONS: Intraoperative pathologic assessment of frozen sections.
      MEASUREMENTS AND MAIN RESULTS: Intraoperative diagnosis of ovarian tumors
      demonstrated sensitivity of 80%, specificity of 99.6%, positive predictive value
      of 80%, and diagnostic accuracy of 99.2%. Mucinous tumors diagnosed
      intraoperatively showed differing intraoperative and final pathologic diagnoses
      significantly more frequently than did other types of tumors. CONCLUSION:
      Intraoperative pathologic assessment of benign ovarian tumors during laparoscopic
      surgery is reliable. However, clinicians should recognize that it is possible to
      make an incorrect diagnosis in some situations and should exercise caution
      accordingly.

PMID- 24333632
TI  - Laparoscopic morcellator-related complications.
AB  - Morcellation at laparoscopy is a commonly used minimally invasive method to
      extract bulky tissue from the abdomen without extending abdominal incisions.
      Despite widespread use of morcellation, complications still remain underreported
      and poorly understood. We performed a systematic review of surgical centers in
      the United States to identify, collate and update the morcellator-related
      injuries and near misses associated with powered tissue removal. We searched
      articles on morcellator-related injuries published from 1993 through June 2013.
      In addition, all cases reported to MedSun and the FDA device database (MAUDE)
      were evaluated for inclusion. We used the search terms "morcellation,"
      "morcellator," "parasitic," and "retained" and model name keywords "Morcellex,"
      "MOREsolution," "PlasmaSORD," "Powerplus," "Rotocut," "SAWALHE," "Steiner," and
      "X-Tract." During the past 15 years, 55 complications were identified. Injuries
      involved the small and large bowels (n = 31), vascular system (n = 27), kidney (n
      = 3), ureter (n = 3), bladder (n = 1), and diaphragm (n = 1). Of these injuries,
      11 involved more than 1 organ. Complications were identified intraoperatively in
      most patients (n = 37 [66%]); however, the remainder were not identified until up
      to 10 days postoperatively. Surgeon inexperience was a contributing factor in
      most cases in which a cause was ascribed. Six deaths were attributed to
      morcellator-related complications. Nearly all major complications were identified
      from the FDA device database and not from the published literature. The
      laparoscopic morcellator has substantially expanded our ability to complete
      procedures using minimally invasive techniques. Associated with this opportunity
      have been increasing reports of major and minor intraoperative complications.
      These complications are largely unreported, likely because of publication bias
      associated with catastrophic events. Surgeon experience likely confers some
      protection against these injuries. Understanding and implementing safe practices
      associated with the use of the laparoscopic morcellator will reduce these
      iatrogenic injuries. 

PMID- 24333633
TI  - S-D-Lactoylglutathione can be an alternative supply of mitochondrial glutathione.
AB  - The mitochondrial pool of GSH (glutathione) is considered the major redox system
      in maintaining matrix redox homeostasis, preserving sulfhydryl groups of
      mitochondrial proteins in appropriate redox state, in defending mitochondrial DNA
      integrity and protecting mitochondrial-derived ROS, and in defending
      mitochondrial membranes against oxidative damage. Despite its importance in
      maintaining mitochondrial functionality, GSH is synthesized exclusively in the
      cytoplasm and must be actively transported into mitochondria. In this work we
      found that SLG (S-D-lactoylglutathione), an intermediate of the glyoxalase
      system, can enter the mitochondria and there be hydrolyzed from mitochondrial
      glyoxalase II enzyme to D-lactate and GSH. To demonstrate SLG transport from
      cytosol to mitochondria we used radiolabeled compounds and the results showed two
      different kinetic curves for SLG or GSH substrates, indicating different kinetic
      transport. Also, the incubation of functionally and intact mitochondria with SLG
      showed increased GSH levels in normal mitochondria and in artificially uncoupled
      mitochondria, demonstrating transport not linked to ATP presence. As well
      mitochondrial-swelling assay confirmed SLG entrance into organelles. Moreover we
      observed oxygen uptake and generation of membrane potential probably linked to D
      lactate oxidation which is a product of SLG hydrolysis. The latter data were
      confirmed by oxidation of D-lactate in mitochondria evaluated by measuring
      mitochondrial D-lactate dehydrogenize activity. In this work we also showed the
      presence of mitochondrial glyoxalase II in inter-membrane space and mitochondrial
      matrix and we investigated the role of SLG in whole cells. In conclusion, this
      work showed new alternative sources of GSH supply to the mitochondria by SLG, an
      intermediate of the glyoxalase system. 

PMID- 24333634
TI  - Role of intracellular labile iron, ferritin, and antioxidant defence in
      resistance of chronically adapted Jurkat T cells to hydrogen peroxide.
AB  - To examine the role of intracellular labile iron pool (LIP), ferritin (Ft), and
      antioxidant defence in cellular resistance to oxidative stress on chronic
      adaptation, a new H2O2-resistant Jurkat T cell line "HJ16" was developed by
      gradual adaptation of parental "J16" cells to high concentrations of H2O2.
      Compared to J16 cells, HJ16 cells exhibited much higher resistance to H2O2
      induced oxidative damage and necrotic cell death (up to 3mM) and had enhanced
      antioxidant defence in the form of significantly higher intracellular glutathione
      and mitochondrial ferritin (FtMt) levels as well as higher glutathione-peroxidase
      (GPx) activity. In contrast, the level of the Ft H-subunit (FtH) in the H2O2
      adapted cell line was found to be 7-fold lower than in the parental J16 cell
      line. While H2O2 concentrations higher than 0.1mM fully depleted the glutathione
      content of J16 cells, in HJ16 cells the same treatments decreased the cellular
      glutathione content to only half of the original value. In HJ16 cells, H2O2
      concentrations higher than 0.1mM increased the level of FtMt up to 4-fold of
      their control values but had no effect on the FtMt levels in J16 cells.
      Furthermore, while the basal cytosolic level of LIP was similar in both cell
      lines, H2O2 treatment substantially increased the cytosolic LIP levels in J16 but
      not in HJ16 cells. H2O2 treatment also substantially decreased the FtH levels in
      J16 cells (up to 70% of the control value). In contrast in HJ16 cells, FtH levels
      were not affected by H2O2 treatment. These results indicate that chronic
      adaptation of J16 cells to high concentrations of H2O2 has provoked a series of
      novel and specific cellular adaptive responses that contribute to higher
      resistance of HJ16 cells to oxidative damage and cell death. These include
      increased cellular antioxidant defence in the form of higher glutathione and FtMt
      levels, higher GPx activity, and lower FtH levels. Further adaptive responses
      include the significantly reduced cellular response to oxidant-mediated
      glutathione depletion, FtH modulation, and labile iron release and a significant
      increase in FtMt levels following H2O2 treatment. 

PMID- 24333635
TI  - A steroid-controlled global switch in sensitivity to apoptosis during Drosophila
      development.
AB  - Precise control over activation of the apoptotic machinery is critical for
      development, tissue homeostasis and disease. In Drosophila, the decision to
      trigger apoptosis--whether in response to developmental cues or to DNA damage-
      converges on transcription of inhibitor of apoptosis protein (IAP) antagonists
      reaper, hid and grim. Here we describe a parallel process that regulates the
      sensitivity to, rather than the execution of, apoptosis. This process establishes
      developmental windows that are permissive or restrictive for triggering
      apoptosis, where the status of cells determines their capacity to die. We
      characterize one switch in the sensitivity to apoptotic triggers, from
      restrictive to permissive, that occurs during third-instar larval (L3)
      development. Early L3 animals are highly resistant to induction of apoptosis by
      expression of IAP-antagonists, DNA-damaging agents and even knockdown of the IAP
      diap1. This resistance to apoptosis, however, is lost in wandering L3 animals
      after acquiring a heightened sensitivity to apoptotic triggers. This switch in
      sensitivity to death activators is mediated by a change in mechanisms available
      for activating endogenous caspases, from an apoptosome-independent to an
      apoptosome-dependent pathway. This switch in apoptotic pathways is regulated in a
      cell-autonomous manner by the steroid hormone ecdysone, through changes in
      expression of critical pro-, but not anti-, apoptotic genes. This steroid
      controlled switch defines a novel, physiologically-regulated, mechanism for
      controlling sensitivity to apoptosis and provides new insights into the control
      of apoptosis during development.

PMID- 24333636
TI  - Primary stress responses in Arabidopsis thaliana exposed to gamma radiation.
AB  - As the environment is inevitably exposed to ionizing radiation from natural and
      anthropogenic sources, it is important to evaluate gamma radiation induced stress
      responses in plants. The objective of this research is therefore to investigate
      radiation effects in Arabidopsis thaliana on individual and subcellular level by
      exposing 2-weeks-old seedlings for 7 days to total doses of 3.9 Gy, 6.7 Gy, 14.8
      Gy and 58.8 Gy and evaluating growth, photosynthesis, chlorophyll a, chlorophyll
      b and carotenoid concentrations and antioxidative enzyme capacities. While the
      capacity of photosystem II (PSII measured as Fv/Fm) remained intact, plants
      started optimizing their photosynthetic process at the lower radiation doses by
      increasing the PSII efficiency (phiPSII) and the maximal electron transport rate
      (ETRmax) and by decreasing the non-photochemical quenching (NPQ). At the highest
      radiation dose, photosynthetic parameters resembled those of control conditions.
      On subcellular level, roots showed increased superoxide dismutase (SOD) and
      ascorbate peroxidase (APX) capacities under gamma irradiation but catalase (CAT),
      syringaldazine peroxidase (SPX) and guaiacol peroxidase (GPX) activities, on the
      other hand, decreased. In the leaves no alterations were observed in SOD, CAT and
      SPX capacities, but GPX was highly affected. Based on these results it seems that
      roots are more sensitive for oxidative stress under gamma radiation exposure than
      leaves.

PMID- 24333637
TI  - Major influencing factors of indoor radon concentrations in Switzerland.
AB  - PURPOSE: In Switzerland, nationwide large-scale radon surveys have been conducted
      since the early 1980s to establish the distribution of indoor radon
      concentrations (IRC). The aim of this work was to study the factors influencing
      IRC in Switzerland using univariate analyses that take into account biases caused
      by spatial irregularities of sampling. METHODS: About 212,000 IRC measurements
      carried out in more than 136,000 dwellings were available for this study. A
      probability map to assess risk of exceeding an IRC of 300 Bq/m(3) was produced
      using basic geostatistical techniques. Univariate analyses of IRC for different
      variables, namely the type of radon detector, various building characteristics
      such as foundation type, year of construction and building type, as well as the
      altitude, the average outdoor temperature during measurement and the lithology,
      were performed comparing 95% confidence intervals among classes of each variable.
      Furthermore, a map showing the spatial aggregation of the number of measurements
      was generated for each class of variable in order to assess biases due to
      spatially irregular sampling. RESULTS: IRC measurements carried out with electret
      detectors were 35% higher than measurements performed with track detectors.
      Regarding building characteristics, the IRC of apartments are significantly lower
      than individual houses. Furthermore, buildings with concrete foundations have the
      lowest IRC. A significant decrease in IRC was found in buildings constructed
      after 1900 and again after 1970. Moreover, IRC decreases at higher outdoor
      temperatures. There is also a tendency to have higher IRC with altitude.
      Regarding lithology, carbonate rock in the Jura Mountains produces significantly
      higher IRC, almost by a factor of 2, than carbonate rock in the Alps. Sedimentary
      rock and sediment produce the lowest IRC while carbonate rock from the Jura
      Mountains and igneous rock produce the highest IRC. Potential biases due to
      spatially unbalanced sampling of measurements were identified for several
      influencing factors. CONCLUSIONS: Significant associations were found between IRC
      and all variables under study. However, we showed that the spatial distribution
      of samples strongly affected the relevance of those associations. Therefore,
      future methods to estimate local radon hazards should take the
      multidimensionality of the process of IRC into account.

PMID- 24333638
TI  - Correlation of unsupported 210Pb activity in soil and moss.
AB  - The activities of unsupported (210)Pb, a naturally occurring radionuclide, were
      measured in samples of soil and terrestrial mosses collected in Serbia.
      Considering that clay particles in soil have a high affinity for Pb adsorption,
      and that mosses usually capture aerosol particles to obtain necessary nutrients,
      measurable amounts of airborne (210)Pb, the daughter of (222)Rn, can be
      registered in both soil and mosses. The objective of the present study was to
      determine if it is possible to compare the activity of unsupported (210)Pb in
      soil and moss collected at the same sampling site, and to establish if a
      correlation exists between these measured values. 

PMID- 24333639
TI  - Contemporary radiation doses to murine rodents inhabiting the most contaminated
      part of the EURT.
AB  - The contemporary radiation doses to the organs and tissues of murine rodents
      inhabiting the most contaminated part of the EURT were estimated. The bones of
      animals trapped in 2005 at territories with a surface (90)Sr contamination of 24
      40 MBq/m(2) were used for dose reconstruction. The concentration of (90)Sr in the
      animals' skulls was measured using the nondestructive method of bone radiometry.
      The dose estimation procedure included application of the published values of
      absorbed fractions of beta-radiation energy for different combinations of source
      and target organs, accounting for the distribution of radionuclide by organs and
      tissues. Twelve conversion coefficients were obtained to link the skeleton (90)Sr
      concentration and doses to eleven organs and the whole body. The whole-body dose
      rate on the 45th day after the beginning of exposure normalised to whole-body
      activity is 0.015 (mGy day(-1))/(Bq g(-1)). The estimation yields the following
      values of doses for Microtus agrestis, Sylvaemus uralensis and Clethrionomys
      rutilus, respectively: maximum absorbed doses in the skeleton: 267, 121 and 160
      mGy; mean whole body internal doses: 37, 14 and 23 mGy; mean internal dose rates
      on the last day before trapping: 1.2; 0.44 and 0.75 mGy/day. Approaches to the
      assessment of doses to foetuses and to offspring before weaning were also
      developed.

PMID- 24333640
TI  - A post-flood co-outbreak of anthrax and enterotoxemia in beef cattle of Liaoning
      Province in north-eastern China.

PMID- 24333641
TI  - Characterization of aroma compounds of Chinese famous liquors by gas
      chromatography-mass spectrometry and flash GC electronic-nose.
AB  - Aroma composition of five Chinese premium famous liquors with different origins
      and liquor flavor types was characterized by gas chromatography-mass spectrometry
      (GC-MS) and flash gas chromatographic electronic nose system. Eighty-six aroma
      compounds were identified, including 5 acids, 34 esters, 10 alcohols, 9
      aldehydes, 4 ketones, 4 phenols, and 10 nitrous and sulfuric compounds. To
      investigate possible correlation between aroma compounds identified by GC-MS and
      sensory attributes, multivariate ANOVA-PLSR (APLSR) was performed. It turned out
      that there were 30 volatile composition, ethyl acetate, ethyl propanoate, ethyl 2
      methyl butanoate, ethyl 3-methyl butanoate, ethyl lactate, ethyl benzenacetate, 3
      methylbutyl acetate, hexyl acetate, 3-methyl-1-butanol, 1-heptanol, phenylethyl
      alcohol, acetaldehyde, 1,1-diethoxy-3-methyl butane, furfural, benzaldehyde, 5
      methyl-2-furanal, 2-octanone, 2-n-butyl furan, dimethyl trisulfied and 2,6
      dimethyl pyrazine, ethyl nonanoate, isopentyl hexanoate, octanoic acid, ethyl 5
      methyl hexanoate, 2-phenylethyl acetate,ethyl oleate, propyl hexanoate, butanoic
      acid and phenol, ethyl benzenepropanoate, which showed good coordination with
      Chinese liquor characteristics. The multivariate structure of this electronic
      nose responses was then processed by principal component analysis (PCA) and
      hierarchical cluster analysis (HCA). According to the obtained results, GC-MS and
      electronic nose can be used for the differentiation of the liquor origins and
      flavor types. 

PMID- 24333642
TI  - Arginine as an eluent for automated on-line Protein A/size exclusion
      chromatographic analysis of monoclonal antibody aggregates in cell culture.
AB  - An automated two-dimensional method using Protein A chromatography followed by
      size exclusion HPLC was developed for analysis of aggregates of monoclonal
      antibodies in mammalian cell culture samples. The method development was intended
      to address the analysis of IgG2 monoclonal antibody products that are
      particularly prone to aggregation at pH<3.5. An aqueous solution of sodium
      phosphate at pH 4.3 containing arginine was demonstrated in this work as an
      excellent eluent for Protein A chromatography. In addition, the arginine solution
      is a compatible mobile phase for the analysis of these samples by size exclusion
      HPLC, separating aggregates from the monomer of the monoclonal antibody. The
      effect of arginine concentration in the eluent on parameters such as protein
      recovery from Protein A chromatography and resolution of aggregates from the
      monomer are reported. The developed method was shown to provide accuracy of
      reported aggregates greater than 98%, and intermediate precision of 4.4% RSD. The
      method limit of quantitation for aggregates was determined to be 0.1%.
      Application of the method is demonstrated for analysis of aggregates in cell
      culture samples to aid in the development of cell culture conditions for the
      production of antibodies. 

PMID- 24333643
TI  - Salicylanilide pyrazinoates inhibit in vitro multidrug-resistant Mycobacterium
      tuberculosis strains, atypical mycobacteria and isocitrate lyase.
AB  - The development of antimicrobial agents represents an up-to-date topic. This
      study investigated in vitro antimycobacterial activity, mycobacterial isocitrate
      lyase inhibition and cytotoxicity of salicylanilide pyrazinoates. They may be
      considered being mutual prodrugs of both antimycobacterial active salicylanilides
      and pyrazinoic acid (POA), an active metabolite of pyrazinamide, in which these
      esters are likely hydrolysed without presence of pyrazinamidase/nicotinamidase.
      Minimum inhibitory concentrations (MICs) of the esters were within the range 0.5
      8 MUmol/l for Mycobacterium tuberculosis and 1-32 MUmol/l for nontuberculous
      mycobacteria (Mycobacterium avium, Mycobacterium kansasii). All esters showed a
      weak inhibition (8-17%) of isocitrate lyase at the concentration of 10 MUmol/l.
      The most active pyrazinoates showed MICs for multidrug-resistant tuberculosis
      strains in the range of 0.125-2 MUmol/l and no cross-resistance with clinically
      used drugs, thus being the most in vitro efficacious salicylanilide esters with 4
      chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate
      superiority (MICs?0.25 MUmol/l). This promising activity is likely due to an
      additive or synergistic effect of released POA and salicylanilides. Selectivity
      indexes for the most active salicylanilide pyrazinoates ranged up to 64, making
      some derivatives being attractive candidates for the next research; 4-bromo-2-{[4
      (trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate showed the most
      convenient toxicity profile.

PMID- 24333644
TI  - Defibrillation out of hospital-the expected role of GPs in China.

PMID- 24333645
TI  - Cardiac arrest prognostic factors in children.

PMID- 24333646
TI  - Stressor controllability modulates fear extinction in humans.
AB  - Traumatic events are proposed to play a role in the development of anxiety
      disorders, however not all individuals exposed to extreme stress experience a
      pathological increase in fear. Recent studies in animal models suggest that the
      degree to which one is able to control an aversive experience is a critical
      factor determining its behavioral consequences. In this study, we examined
      whether stressor controllability modulates subsequent conditioned fear expression
      in humans. Participants were randomly assigned to an escapable stressor
      condition, a yoked inescapable stressor condition, or a control condition
      involving no stress exposure. One week later, all participants underwent fear
      conditioning, fear extinction, and a test of extinction retrieval the following
      day. Participants exposed to inescapable stress showed impaired fear extinction
      learning and increased fear expression the following day. In contrast, escapable
      stress improved fear extinction and prevented the spontaneous recovery of fear.
      Consistent with the bidirectional controllability effects previously reported in
      animal models, these results suggest that one's degree of control over aversive
      experiences may be an important factor influencing the development of
      psychological resilience or vulnerability in humans. 

PMID- 24333647
TI  - Voluntary exercise followed by chronic stress strikingly increases mature adult
      born hippocampal neurons and prevents stress-induced deficits in 'what-when
      where' memory.
AB  - We investigated whether voluntary exercise prevents the deleterious effects of
      chronic stress on episodic-like memory and adult hippocampal neurogenesis. After
      bromodeoxyuridine (BrdU) administration, mice were assigned to receive standard
      housing, chronic intermittent restraint stress, voluntary exercise or a
      combination of both (stress starting on the seventh day of exercise). Twenty-four
      days later, mice were tested in a 'what-when-where' object recognition memory
      task. Adult hippocampal neurogenesis (proliferation, differentiation, survival
      and apoptosis) and c-Fos expression in the hippocampus and extra-hippocampal
      areas (medial prefrontal cortex, amygdala, paraventricular hypothalamic nucleus,
      accumbens and perirhinal cortex) were assessed after behavior. Chronic
      intermittent restraint stress impaired neurogenesis and the 'when' memory, while
      exercise promoted neurogenesis and improved the 'where' memory. The 'when' and
      'where' memories correlated with c-Fos expression in CA1 and the dentate gyrus,
      respectively. Furthermore, analysis suggested that each treatment induced a
      distinct pattern of functional connectivity among the areas analyzed for c-Fos.
      In the animals in which stress and exercise were combined, stress notably reduced
      the amount of voluntary exercise performed. Nevertheless, exercise still improved
      memory and counteracted the stress induced-deficits in neurogenesis and behavior.
      Interestingly, compared with the other three treatments, the stressed exercising
      animals showed a larger increase in cell survival, the maturation of new neurons
      and apoptosis in the dentate gyrus, with a considerable increase in the number of
      24-day-old BrdU+cells that differentiated into mature neurons. The interaction
      between exercise and stress in enhancing the number of adult-born hippocampal
      neurons supports a role of exercise-induced neurogenesis in stressful conditions.

PMID- 24333648
TI  - Heart rate response to post-learning stress predicts memory consolidation.
AB  - Stressful experiences are often well remembered, an effect that has been
      explained by beta-adrenergic influences on memory consolidation. Here, we studied
      the impact of stress induced heart rate (HR) responses on memory consolidation in
      a post-learning stress paradigm. 206 male and female participants saw 52 happy
      and angry faces immediately before being exposed to the Cold Pressor Test or a
      non-stressful control procedure. Memory for the faces and their respective
      expression was tested twice, after 30 min and on the next day. High HR responders
      (in comparison to low HR responders as well as to the non-stressful control
      group) showed enhanced recognition memory one day after learning. Our results
      show that beta-adrenergic activation elicited shortly after learning enhances
      memory consolidation and that the stress induced HR response is a predictor for
      this effect.

PMID- 24333649
TI  - "There are decades where nothing happens; and there are weeks where decades
      happen"--Vladimir Ilyich Lenin.

PMID- 24333650
TI  - A systematic review and meta-analysis of 'Systems for Social Processes' in eating
      disorders.
AB  - Social and emotional problems have been implicated in the development and
      maintenance of eating disorders (ED). This paper reviews the facets of social
      processing in ED according to the NIMH Research and Domain Criteria (NIMH RDoC)
      'Systems for Social Processes' framework. Embase, Medline, PsycInfo and Web of
      Science were searched for peer-reviewed articles published by March 2013. One
      hundred and fifty four studies measuring constructs of: attachment, social
      communication, perception and understanding of self and others, and social
      dominance in people with ED, were identified. Eleven meta-analyses were
      performed, they showed evidence that people with ED had attachment insecurity
      (d=1.31), perceived low parental care (d=.51), appraised high parental
      overprotection (d=0.29), impaired facial emotion recognition (d=.44) and facial
      communication (d=2.10), increased facial avoidance (d=.52), reduced agency
      (d=.39), negative self-evaluation (d=2.27), alexithymia (d=.66), poor
      understanding of mental states (d=1.07) and sensitivity to social dominance
      (d=1.08). There is less evidence for problems with production and reception of
      non-facial communication, animacy and action. 

PMID- 24333651
TI  - Reproduction of honeybee workers is regulated by epidermal growth factor receptor
      signaling.
AB  - Eusocial insect societies display a remarkable reproductive division of labor
      between a single fertile queen and thousands of largely sterile workers. In most
      species, however, the workers retain the capacity to reproduce, particularly in
      queenless colonies where typically many workers lay eggs. As yet, the molecular
      determinants that initiate this shift in worker fertility are still poorly
      documented. By using RNA interference we here demonstrate that the knockdown of
      epidermal growth factor receptor, a gene which was previously shown to be
      involved in queen-worker caste differentiation, also induces reproduction in
      worker honeybees (Apis mellifera). These data show that worker fertility and
      queen-worker caste determination partly rely on the same gene regulatory
      networks, thereby providing a major breakthrough in our understanding of the
      molecular determinants of the social insects' spectacular reproductive division
      of labor. 

PMID- 24333652
TI  - Functional assays to define agonists and antagonists of the sigma-2 receptor.
AB  - The sigma-2 receptor has been identified as a biomarker in proliferating tumors.
      To date there is no well-established functional assay for defining sigma-2
      agonists and antagonists. Many sigma-2 ligands with diverse structures have been
      shown to induce cell death in a variety of cancer cells by triggering caspase
      dependent and independent apoptosis. Therefore, in the current study, we used the
      cell viability assay and the caspase-3 activity assay to determine sigma-2
      agonists and antagonists. Three classes of sigma-2 ligands developed in our
      laboratory were evaluated for their potency to induce cell death in two tumor
      cell lines, mouse breast cancer cell line EMT-6 and human melanoma cell line MDA
      MB-435. The data showed that the EC50 values of the sigma-2 ligands using the
      cell viability assay ranged from 11.4MUM to >200MUM, which were comparable with
      the EC50 values obtained using the caspase-3 assay. Based on the cytotoxicity of
      a sigma-2 ligand relative to that of siramesine, a commonly accepted sigma-2
      agonist, we have categorized our sigma-2 ligands into agonists, partial agonists,
      and antagonists. The establishment of functional assays for defining sigma-2
      agonists and antagonists will facilitate functional characterization of sigma-2
      receptor ligands and sigma-2 receptors. 

PMID- 24333653
TI  - Poly(ADP-ribose) polymerase-1 and its cleavage products differentially modulate
      cellular protection through NF-kappaB-dependent signaling.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) and its cleavage products regulate cell
      viability and NF-kappaB activity when expressed in neurons. PARP-1 cleavage
      generates a 24 kDa (PARP-1(24)) and an 89 kDa fragment (PARP-1(89)). Compared to
      WT (PARP-1WT), the expression of an uncleavable PARP-1 (PARP-1(UNCL)) or of PARP
      1(24) conferred protection from oxygen/glucose deprivation (OGD) or
      OGD/restoration of oxygen and glucose (ROG) damage in vitro, whereas expression
      of PARP-1(89) was cytotoxic. Viability experiments were performed in SH-SY5Y, a
      human neuroblastoma cell line, as well as in rat primary cortical neurons.
      Following OGD, the higher viability in the presence of PARP-1UNCL or PARP-1(24)
      was not accompanied with decreased formation of poly(ADP-riboses) or higher NAD
      levels. PARP-1 is a known cofactor for NF-kappaB, hence we investigated whether
      PARP-1 cleavage influences the inflammatory response. All PARP-1 constructs
      mimicked PARP-1WT in regard to induction of NF-kappaB translocation into the
      nucleus and its increased activation during ischemic challenge. However,
      expression of PARP-1(89) construct induced significantly higher NF-kB activity
      than PARP-1WT; and the same was true for NF-kappaB-dependent iNOS promoter
      binding activity. At a protein level, PARP-1UNCL and PARP-1(24) decreased iNOS
      (and lower levels of iNOS transcript) and COX-2, and increased Bcl-xL The
      increased levels of NF-kB and iNOS transcriptional activities, seen with
      cytotoxic PARP-189, were accompanied by higher protein expression of COX-2 and
      iNOS (and higher levels of INOS transcript) and lower protein expression of Bcl
      xL Taken together, these findings suggest that PARP-1 cleavage products may
      regulate cellular viability and inflammatory responses in opposing ways during in
      vitro models of "ischemia".

PMID- 24333654
TI  - Plasma adrenomedullin levels are associated with long-term outcomes of acute
      ischemic stroke.
AB  - Plasma adrenomedullin concentration has been found to be enhanced in ischemic
      stroke. Up to now, little is known about the association of plasma adrenomedullin
      concentration with clinical outcomes of ischemic stroke. This study recruited 138
      patients with ischemic stroke and 138 healthy volunteers. Unfavorable outcome was
      defined as modified Rankin Scale score >2 at 3 months. Plasma adrenomedullin
      concentrations were determined by enzyme-linked immunosorbent assay. Plasma
      adrenomedullin concentrations were statistically significantly higher in patients
      than in healthy individuals (79.9+/-27.3pg/mL vs. 36.8+/-10.4pg/mL; P<0.001). 3
      Month mortality was 20.3% (28/138) and sixty-six patients (47.8%) had unfavorable
      outcome in 3 months. A logistic regression analysis identified plasma
      adrenomedullin concentration as an independent predictor of 3-month mortality
      (odds ratio, 1.211; 95% confidence interval, 1.101-1.582; P=0.004) and
      unfavorable outcome (odds ratio, 1.193; 95% confidence interval, 1.082-1.447;
      P=0.006). Receiver operating characteristic curve analysis showed that plasma
      adrenomedullin concentration predicted 3-month mortality (area under curve,
      0.806; 95% confidence interval, 0.730-0.868) and unfavorable outcome (area under
      curve, 0.816; 95% confidence interval, 0.742-0.877) with the high predictive
      value. Its predictive performance was similar to that of National Institutes of
      Health Stroke Scale score (P=0.694 or 0.206). Its combined use with National
      Institutes of Health Stroke Scale score did not improve the predictive value
      (P=0.236 or 0.590). Thus, adrenomedullin may aid to predict long-term clinical
      outcomes of patients with ischemic stroke. 

PMID- 24333655
TI  - Obestatin and cardiovascular health.
AB  - Obestatin, encoded by the same gene as ghrelin, was first described as a
      physiological opponent of ghrelin through an interaction with the orphan receptor
      GPR39. However, the effects of obestatin were not totally contrary to the effects
      of ghrelin in cardiovascular regulations based on the recent studies. We
      summarize here the current evidences surrounding the cardiovascular actions of
      obestatin, and the possible implications of obestatin as a therapeutic agent in
      common conditions such as hypertension and heart failure. 

PMID- 24333656
TI  - Plasma C-terminal proEndothelin-1 (CTproET-1) is affected by age, renal function,
      left atrial size and diastolic blood pressure in healthy subjects.
AB  - Endothelin-1 (ET-1) is a short chained peptide primarily of endothelial origin.
      Concentrations of this peptide are increased in subjects with hypertension,
      primary pulmonary hypertension and myocardial infarction, however its short half
      life makes quantification difficult. The C-terminal of proET-1 (CTproET-1) is
      stoichiometrically secreted with its bioactive peptide and would be a valid
      method of measuring the active peptide as it has a stable half-life and is less
      resistant to proteolytic cleavage. The objective of this study was to understand
      the factors (clinical, echocardiographic and biochemical) that specifically
      influence plasma CTproET-1 in healthy subjects. 518 healthy volunteers were
      recruited from a screening study. Plasma CTproET-1 concentrations were quantified
      using a novel immunoluminometric sandwich assay. In multivariate analyses, age
      (P<0.001), diastolic BP (P=0.007), LA size (P=0.001) and eGFR (P<0.001) were
      independently predictive of plasma CTproET-1 levels in the healthy subjects.
      Therefore the interpretation of plasma CTproET-1 levels in such individuals
      should take into account these variables to avoid potential confounding. 

PMID- 24333657
TI  - Evaluation of an implementation initiative for embedding Dialectical Behavior
      Therapy in community settings.
AB  - We examined the effectiveness of Dialectical Behavior Therapy (DBT) training in
      community-based agencies. Data were gathered at four time points over a 2-year
      period from front-line mental health therapists (N=64) from 10 community-based
      agencies that participated in a DBT implementation initiative. We examined change
      on therapist attitudes toward consumers with Borderline Personality Disorder
      (BPD), confidence in the effectiveness of DBT, and use of DBT model components.
      All measures were self-report. Participating in DBT training was associated with
      positive changes over time, including improved therapist attitudes toward
      consumers with BPD, improved confidence in the effectiveness of DBT, and
      increased use of DBT components. Therapists who had the lowest baseline scores on
      the study outcomes had the greatest self-reported positive change in outcomes
      over time. Moreover, there were notable positive correlations in therapist
      characteristics; therapists who had the lowest baseline attitudes toward
      individuals with BPD, confidence in the effectiveness of DBT, or who were least
      likely to use DBT modes and components were the therapists who had the greatest
      reported increase over time in each respective area. DBT training with ongoing
      support resulted in changes not commonly observed in standard training approaches
      typically used in community settings. It is encouraging to observe positive
      outcomes in therapist self-reported skill, perceived self-efficacy and DBT
      component use, all of which are important to evidence-based treatment (EBT)
      implementation. Our results underscore the importance to recognize and target
      therapist diversity of learning levels, experience, and expertise in EBT
      implementation. 

PMID- 24333659
TI  - Particulate air pollution and mortality in a cohort of Chinese men.
AB  - Few prior cohort studies exist in developing countries examining the association
      of ambient particulate matter (PM) with mortality. We examined the association of
      particulate air pollution with mortality in a prospective cohort study of 71,431
      middle-aged Chinese men. Baseline data were obtained during 1990-1991. The follow
      up evaluation was completed in January, 2006. Annual average PM exposure between
      1990 and 2005, including TSP and PM10, were estimated by linking fixed-site
      monitoring data with residential communities. We found significant associations
      between PM10 and mortality from cardiopulmonary diseases; each 10 MUg/m(3) PM10
      was associated with a 1.6% (95%CI: 0.7%, 2.6%), 1.8% (95%CI: 0.8%, 2.9%) and 1.7%
      (95%CI: 0.3%, 3.2%) increased risk of total, cardiovascular and respiratory
      mortality, respectively. For TSP, we observed significant associations only for
      cardiovascular morality. These data contribute to the scientific literature on
      long-term effects of particulate air pollution for high exposure settings typical
      in developing countries.

PMID- 24333658
TI  - Expression of LIM-homeodomain transcription factors in the developing and mature
      mouse retina.
AB  - LIM-homeodomain (LIM-HD) transcription factors have been extensively studied for
      their role in the development of the central nervous system. Their function is
      key to several developmental events like cell proliferation, differentiation and
      subtype specification. However, their roles in retinal neurogenesis remain
      largely unknown. Here we report a detailed expression study of LIM-HD
      transcription factors LHX9 and LHX2, LHX3 and LHX4, and LHX6 in the developing
      and mature mouse retina using immunohistochemistry and in situ hybridization
      techniques. We show that LHX9 is expressed during the early stages of development
      in the retinal ganglion cell layer and the inner nuclear layer. We also show that
      LHX9 is expressed in a subset of amacrine cells in the adult retina. LHX2 is
      known to be expressed in retinal progenitor cells during development and in
      Muller glial cells and a subset of amacrine cells in the adult retina. We found
      that the LHX2 subset of amacrine cells is not cholinergic and that a very few of
      LHX2 amacrine cells express calretinin. LHX3 and LHX4 are expressed in a subset
      of bipolar cells in the adult retina. LHX6 is expressed in cells in the ganglion
      cell layer and the neuroblast layer starting at embryonic stage 13.5 (E13.5) and
      continues to be expressed in cells in the ganglion cell layer and inner nuclear
      layer, postnatally, suggesting its likely expression in amacrine cells or a
      subset thereof. Taken together, our comprehensive assay of expression patterns of
      LIM-HD transcription factors during mouse retinal development will help further
      studies elucidating their biological functions in the differentiation of retinal
      cell subtypes. 

PMID- 24333660
TI  - Transport of perfluoroalkyl acids in a water-saturated sediment column
      investigated under near-natural conditions.
AB  - The aim of this study was to gain an understanding of the transport of C4-10
      perfluoroalkyl carboxylic acids (PFCAs) and C4,6,8 perfluoroalkyl sulfonic acids
      (PFSAs) in a water-saturated sediment column representing a riverbank filtration
      scenario under near-natural conditions. Short-chain PFCAs and PFSAs with up to
      six C-atoms showed complete tracer-like breakthrough. Longer chain ones were
      retarded due to sorption to the sediment or due to other processes in the aqueous
      phase. The study reports the first column derived sediment-water partition
      coefficients ranging from 0.01 cm(3) g(-1) to 0.41 cm(3) g(-1) for C4,6 PFSAs and
      from 0.0 cm(3) g(-1) to 6.5 cm(3) g(-1) for C4,5,6,8,9 PFCAs. The results clearly
      indicate that short-chain PFCAs and PFSAs may pose a problem if contaminated
      surface waters are used for drinking water production via riverbank filtration.

PMID- 24333661
TI  - Pharmacological modulation of I(1)-imidazoline and alpha2-adrenoceptors in sub
      acute brain ischemia induced vascular dementia.
AB  - Sub-acute brain ischemia is a risk factor for the development of vascular
      dementia (VaD). Sub-acute brain ischemia induced VaD, participates in a negative
      role in impaired cognition. Imidazoline receptors are widely expressed in the
      central nervous system. But the role of I1-imidazoline and alpha2-adrenoceptors
      in VaD are still unknown. The present study has been designed to investigate the
      role of selective I1-imidazoline receptor modulator; moxonidine as well as alpha2
      adrenoceptor modulator; clonidine in sub-acute brain ischemia induced VaD in mice
      (n=8). Permanent bilateral common carotid arteries ligation (2VO) technique was
      used to induce sub-acute brain ischemia in mice. Assessment of spatial learning
      and memory was done by using Morris water maze. Brain damage was assessed as
      percent infarct, using TTC staining of brain coronal sections. Oxidative stress
      was assessed by estimating brain malondialdehyde (MDA), catalase (CAT),
      glutathione (GSH) and superoxide dismutase (SOD). Cholinergic status was assessed
      by brain acetylcholinesterase (AChE) activity. 2VO animals have shown significant
      reduction in learning and memory as well as brain CAT, GSH and SOD, with
      significant increase in brain infarct size, MDA and AChE activity. Whereas,
      administration of moxonidine and clonidine significantly attenuated 2VO induced
      learning and memory deficits, brain damage, brain oxidative stress and higher
      AChE activity. It may be concluded that 2VO induced sub-acute brain ischemia has
      elicited dementia, which was attenuated by moxonidine and clonidine. Thus,
      modulators of I1-imidazoline receptors may be explored further for their benefits
      in sub-acute brain ischemia induced vascular dementia. 

PMID- 24333662
TI  - CD14(bright)CD16(low) intermediate monocytes expressing Tie2 are increased in the
      peripheral blood of patients with primary myelofibrosis.

PMID- 24333663
TI  - Flk2/Flt3 promotes both myeloid and lymphoid development by expanding non-self
      renewing multipotent hematopoietic progenitor cells.
AB  - Defining differentiation pathways is central to understanding the pathogenesis of
      hematopoietic disorders, including leukemia. The function of the receptor
      tyrosine kinase Flk2 (Flt3) in promoting myeloid development remains poorly
      defined, despite being commonly mutated in acute myeloid leukemia. We
      investigated the effect of Flk2 deficiency on myelopoiesis, focusing on
      specification of progenitors between HSC and mature cells. We provide evidence
      that Flk2 is critical for proliferative expansion of multipotent progenitors that
      are common precursors for all lymphoid and myeloid lineages, including
      megakaryocyte/erythroid (MegE) cells. Flk2 deficiency impaired the generation of
      both lymphoid and myeloid progenitors by abrogating propagation of their common
      upstream precursor. At steady state, downstream compensatory mechanisms masked
      the effect of Flk2 deficiency on mature myeloid output, whereas transplantation
      of purified progenitors revealed impaired generation of all mature lineages. Flk2
      deficiency did not affect lineage choice, thus dissociating the role of Flk2 in
      promoting cell expansion and regulating cell fate. Surprisingly, despite
      impairing myeloid development, Flk2 deficiency afforded protection against
      myeloablative insult. This survival advantage was attributed to reduced cell
      cycling and proliferation of progenitors in Flk2-deficient mice. Our data support
      the existence of a common Flk2(+) intermediate for all hematopoietic lineages and
      provide insight into how activating Flk2 mutations promote hematopoietic
      malignancy by non-Flk2-expressing myeloid cells. 

PMID- 24333664
TI  - Determination of dependencies among in vitro and in vivo properties of prepared
      mucoadhesive buccal films using multivariate data analysis.
AB  - Mucoadhesive films represent the most developed medical form of buccal
      application. Despite the intense focus on buccal film-based systems, there are no
      standardized methods for their evaluation, which limits the possibility of
      comparison of obtained data and evaluation of the significance of influence of
      formulation and process variables on properties of resulting films. The used
      principal component analysis, together with a partial least squares regression
      provided a unique insight into the effects of in vitro parameters of mucoadhesive
      buccal films on their in vivo properties and into interdependencies among the
      studied variables. In the present study eight various mucoadhesive buccal films
      based on mucoadhesive polymers (carmellose, polyethylene oxide) were prepared
      using a solvent casting method or a method of impregnation, respectively. An
      ethylcellulose or hydrophobic blend of white beeswax and white petrolatum were
      used as a backing layer. The addition of polyethylene oxide prolonged the in vivo
      film residence time (from 53.24+/-5.38-74.18+/-5.13 min to 71.05+/-3.15-98.12+/
      1.75 min), and even more when combined with an ethylcellulose backing layer
      (98.12+/-1.75 min) and also improved the film's appearance. Tested non-woven
      textile shortened the in vivo film residence time (from 74.18+/-5.13-98.12+/-1.75
      min to 53.24+/-5.38-81.00+/-8.47 min) and generally worsened the film's
      appearance. Mucoadhesive buccal films with a hydrophobic backing layer were
      associated with increased frequency of adverse effects.

PMID- 24333665
TI  - Design, synthesis and in vitro evaluation of mucoadhesive p-coumarate-thiolated
      chitosan as a hydrophobic drug carriers.
AB  - A hydrophobic mucoadhesive thiolated chitosan for hydrophobic drug delivery was
      designed and prepared by conjugating p-coumaric acid (pCA) to increase
      hydrophobic compatibility with drug via pi-pi interaction and then covalently
      linking homocysteine thiolactone (HT) to the pCA-chitosan to increase the
      mucoadhesive properties. The degree of substituted phenolics in the modified
      chitosan was about 7.21+/-0.05 mg gallic acid equivalents (GAE)/g. The pCA-HT
      chitosan formed from a 24 h HT conjugation reaction time showed the highest yield
      of grafted thiol groups (~17.6 MUmol/g) and the strongest mucoadhesive property,
      being about 10-, 2- and 1.6-fold more than that for the unmodified chitosan at pH
      1.2, 4.0 and 6.4, respectively. Piperine (PIP) as a model hydrophobic drug was
      encapsulated in pCA-HT-chitosan microparticles via electrospray ionization with
      an encapsulation efficiency of over 80%. In vitro release studies showed a
      sustained release of PIP to >75% over 12 h between pH 1.2 and 6.4.

PMID- 24333666
TI  - Evaluation of Shirasu Porous Glass (SPG) membrane emulsification for the
      preparation of colloidal lipid drug carrier dispersions.
AB  - Aqueous colloidal drug carrier dispersions based on nonpolar lipids are usually
      prepared by high energy dispersion techniques, like high-pressure homogenization.
      Homogenization generates high shear forces and may thus not be suitable for the
      processing of sensitive pharmaceutical ingredients, e.g., proteins. This study
      investigated the general possibility to prepare lipid nanoparticle dispersions by
      direct and premix Shirasu Porous Glass (SPG) membrane emulsification as
      alternative low energy and low shear method. The influence of different
      emulsifiers (polysorbate 20, sorbitan oleate, poloxamer 188, sodium dodecyl
      sulfate, sucrose laurate), the type of lipid phase (medium chain triglycerides,
      soybean oil, trimyristin, glyceryl behenate, lauroyl macrogolglycerides), the
      pore size of the SPG membrane (0.1, 0.2, 0.3, 0.5, 1.1MUm) and the emulsifying
      pressure on the particle size of the resulting dispersions was investigated. The
      particle size was primarily controlled by the pore size of the membrane and the
      emulsifying pressure. Very narrow particle size distributions with membrane pore
      size/mean particle size ratios of 1:0.4-1:8.2 and 1:0.4-1:2.1 were observed for
      the direct and the premix membrane emulsification method, respectively. Due to
      the comparatively lower process pressures of at maximum 10bar SPG membrane
      emulsification is an interesting alternative method to high-pressure
      homogenization. 

PMID- 24333667
TI  - Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A
      pathways in chicken micromass cultures.
AB  - Biomechanical stimuli play important roles in the formation of articular
      cartilage during early foetal life, and optimal mechanical load is a crucial
      regulatory factor of adult chondrocyte metabolism and function. In this study, we
      undertook to analyse mechanotransduction pathways during in vitro chondrogenesis.
      Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were
      cultivated as high density cell cultures for 6 days. Mechanical stimulation was
      carried out by a self-designed bioreactor that exerted uniaxial intermittent
      cyclic load transmitted by the culture medium as hydrostatic pressure and fluid
      shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min)
      was applied on culturing days 2 and 3, when final commitment and differentiation
      of chondroprogenitor cells occurred in this model. The applied mechanical load
      significantly augmented cartilage matrix production and elevated mRNA expression
      of several cartilage matrix constituents, including collagen type II and aggrecan
      core protein, as well as matrix-producing hyaluronan synthases through enhanced
      expression, phosphorylation and nuclear signals of the main chondrogenic
      transcription factor Sox9. Along with increased cAMP levels, a significantly
      enhanced protein kinase A (PKA) activity was also detected and CREB, the
      archetypal downstream transcription factor of PKA signalling, exhibited elevated
      phosphorylation levels and stronger nuclear signals in response to mechanical
      stimuli. All the above effects were diminished by the PKA-inhibitor H89.
      Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197
      resulted in enhanced cartilage formation, which was additive to that of the
      mechanical stimulation, implying that the chondrogenesis-promoting effect of
      mechanical load was independent of Epac. At the same time, PP2A activity was
      reduced following mechanical load and treatments with the PP2A-inhibitor okadaic
      acid were able to mimic the effects of the intervention. Our results indicate
      that proper mechanical stimuli augment in vitro cartilage formation via promoting
      both differentiation and matrix production of chondrogenic cells, and the
      opposing regulation of the PKA/CREB-Sox9 and the PP2A signalling pathways is
      crucial in this phenomenon.

PMID- 24333668
TI  - Luteolin sensitizes the antiproliferative effect of interferon alpha/beta by
      activation of Janus kinase/signal transducer and activator of transcription
      pathway signaling through protein kinase A-mediated inhibition of protein
      tyrosine phosphatase SHP-2 in cancer cells.
AB  - New negative regulators of interferon (IFN) signaling, preferably with tissue
      specificity, are needed to develop therapeutic means to enhance the efficacy of
      type I IFNs (IFN-alpha/beta) and reduce their side effects. We conducted cell
      based screening for IFN signaling enhancer and discovered that luteolin, a
      natural flavonoid, sensitized the antiproliferative effect of IFN-alpha in
      hepatoma HepG2 cells and cervical carcinoma HeLa cells. Luteolin promoted IFN
      beta-induced Janus kinase/signal transducer and activator of transcription
      (JAK/STAT) pathway activation by enhancing the phosphorylation of Jak1, Tyk2, and
      STAT1/2, thereby promoting STAT1 accumulation in the nucleus and endogenous IFN
      alpha-regulated gene expression. Of interest, inhibition of phosphodiesterase
      (PDE) abolished the effect of IFN-beta and luteolin on STAT1 phosphorylation.
      Luteolin also increased the cAMP-degrading activity of PDE bound with type I
      interferon receptor 2 (IFNAR2) and decreased the intracellular cAMP level,
      indicating that luteolin may act on the JAK/STAT pathway via PDE. Protein kinase
      A (PKA) was found to negatively regulate IFN-beta-induced JAK/STAT signaling, and
      its inhibitory effect was counteracted by luteolin. Pull-down and
      immunoprecipitation assays revealed that type II PKA interacted with IFNAR2 via
      the receptor for activated C-kinase 1 (RACK-1), and such interaction was
      inhibited by luteolin. Src homology domain 2 containing tyrosine phosphatase-2
      (SHP-2) was further found to mediate the inhibitory effect of PKA on the JAK/STAT
      pathway. These data suggest that PKA/PDE-mediated cAMP signaling, integrated by
      RACK-1 to IFNAR2, may negatively regulate IFN signaling through SHP-2. Inhibition
      of this signaling may provide a new way to sensitize the efficacy of IFN
      alpha/beta. 

PMID- 24333670
TI  - Caffeine induces tumor cytotoxicity via the regulation of alternative splicing in
      subsets of cancer-associated genes.
AB  - Caffeine causes a diverse range of pharmacological effects that are time- and
      concentration-dependent and reversible. The detailed mechanisms of caffeine in
      tumor suppression via tumor suppressor protein p53 remain unclear. The isoforms
      of p53 are physiological proteins that are expressed in normal cells and
      generated via alternative promoters, splicing sites and/or translational
      initiation sites. In this study, we investigated how caffeine modulated cell
      cycle arrest and apoptosis via the expression of various alternatively spliced
      p53 isoforms. Caffeine reduced p53alpha expression and induced the expression of
      p53beta, which contains an alternatively spliced p53 C-terminus. In HeLa cells,
      the expression levels of many serine/arginine-rich splicing factors, including
      serine/arginine-rich splicing factors 2 and 3, were altered by caffeine.
      Serine/arginine-rich splicing factor 3 was a promising candidate for the
      serine/arginine-rich splicing factors responsible for the alternative splicing of
      p53 in response to caffeine treatment. In addition to p53-dependent functions,
      multiple target genes of serine/arginine-rich splicing factor 3 suggest that
      caffeine can regulate epithelial-mesenchymal-transition and hypoxic conditions to
      inhibit the survival of tumor cells. In summary, our data provide a new pathway
      of caffeine-modulated tumor suppression via the alternative splicing of the
      target genes of serine/arginine-rich splicing factor 3. 

PMID- 24333671
TI  - Transcription factor C/EBPbeta and 17beta-estradiol promote transcription of the
      porcine p53 gene.
AB  - The tumor protein 53 (p53) gene played a crucial role in maternal reproduction
      except its classic roles in maintaining genomic stability and preventing
      tumorigenesis. However, little is known concerning the regulatory elements which
      control the expression of p53 gene. In this study, we predicted two binding sites
      (-490/-477 and -405/-392) of transcription factor CCAAT/enhancer binding protein
      beta (C/EBPbeta) within the core promoter (-985/-273) determined by promoter
      deletion analysis, and discovered that the second site (-405/-392) was important
      for p53 promoter activity by site-directed mutagenesis. Then the binding of
      C/EBPbeta to the p53 promoter was identified by electrophoretic mobility shift
      assays (EMSA) and chromatin immunoprecipitation (ChIP). Moreover, evidence from
      C/EBPbeta overexpression and RNAi studies showed C/EBPbeta regulated p53 promoter
      activity and endogenous p53 expression. Meanwhile, we observed p53 mRNA at the
      peak in 10(-6)mol/L 17beta-estradiol treated cells for 24h via enhancing its core
      promoter activity. Taken together, our study indicates that C/EBPbeta and 17beta
      estradiol are the essential regulatory factors for p53 transcription. 

PMID- 24333672
TI  - Tribological properties of biocompatible Ti-10W and Ti-7.5TiC-7.5W.
AB  - This study investigates and compares the microstructure, biocompatibility, and
      tribological properties of two different Ti-based composites, Ti-10W and Ti
      7.5TiC-7.5W, with those of pure Ti for their potential use in biomedical
      applications. In particular, cold and hot isostatic-pressing and arc-melting
      methods were utilized and compared for the microstructure of the composites. Nano
      scratch measurements and pin-on-disk wear tests were employed to understand their
      tribological behavior. As compared to pure Ti, Ti-10W and Ti-7.5TiC-7.5W showed
      significantly improved nano-scratch resistance (by 85 and 77%, respectively) and
      wear resistance (by 64 and 66%, respectively), in good agreement with hardness
      measurements. For biocompatibility examination, both microculture tetrazolium
      test (MTT) and water soluble tetrazolium (WST-1) test were used to quantify the
      cell viability of human osteoblasts and mouse fibroblasts on the materials. Both
      of the Ti-based composites showed acceptable biocompatibility in comparison with
      the pure Ti control. 

PMID- 24333673
TI  - Bending mechanics of the red-eared slider turtle carapace.
AB  - The turtle shell is a natural shield that possesses complex hierarchical
      structure, giving rise to superior mechanical properties. The keratin-covered
      boney top (dorsal) part of the shell, termed carapace, is composed of rigid
      sandwich-like ribs made of a central foam-like interior flanked by two external
      cortices. The ribs are attached to one another in a 3-D interdigitated manner at
      soft unmineralized collagenous sutures. This unique structural combination
      promotes sophisticated mechanical response upon predator attacks. In the present
      study mechanical bending tests were performed to examine the static behavior of
      the red-eared slider turtle carapace, in different orientations and from various
      locations, as well as from whole-rib and sub-layer regions. In addition, the
      suture properties were evaluated as well and compared with those of the rib. A
      simplified classical analysis was used here to rationalize the experimental
      results of the whole rib viewed as a laminated composite. The measured strength
      (~300MPa) and bending modulus (~7-8.5GPa) of the rib were found to be of the same
      order of magnitude as the strength and modulus of the cortices. The theoretical
      prediction of the ribs' moduli, predicted in terms of the individual sub-layers
      moduli, agreed well with the experimental results. The suture regions were found
      to be more compliant and weaker than the ribs, but comparatively tough, likely
      due to the interlocking design of the boney zigzag elements. 

PMID- 24333669
TI  - Circadian organization of the mammalian retina: from gene regulation to
      physiology and diseases.
AB  - The retinal circadian system represents a unique structure. It contains a
      complete circadian system and thus the retina represents an ideal model to study
      fundamental questions of how neural circadian systems are organized and what
      signaling pathways are used to maintain synchrony of the different structures in
      the system. In addition, several studies have shown that multiple sites within
      the retina are capable of generating circadian oscillations. The strength of
      circadian clock gene expression and the emphasis of rhythmic expression are
      divergent across vertebrate retinas, with photoreceptors as the primary locus of
      rhythm generation in amphibians, while in mammals clock activity is most robust
      in the inner nuclear layer. Melatonin and dopamine serve as signaling molecules
      to entrain circadian rhythms in the retina and also in other ocular structures.
      Recent studies have also suggested GABA as an important component of the system
      that regulates retinal circadian rhythms. These transmitter-driven influences on
      clock molecules apparently reinforce the autonomous transcription-translation
      cycling of clock genes. The molecular organization of the retinal clock is
      similar to what has been reported for the SCN although inter-neural communication
      among retinal neurons that form the circadian network is apparently weaker than
      those present in the SCN, and it is more sensitive to genetic disruption than the
      central brain clock. The melatonin-dopamine system is the signaling pathway that
      allows the retinal circadian clock to reconfigure retinal circuits to enhance
      light-adapted cone-mediated visual function during the day and dark-adapted rod
      mediated visual signaling at night. Additionally, the retinal circadian clock
      also controls circadian rhythms in disk shedding and phagocytosis, and possibly
      intraocular pressure. Emerging experimental data also indicate that circadian
      clock is also implicated in the pathogenesis of eye disease and compelling
      experimental data indicate that dysfunction of the retinal circadian system
      negatively impacts the retina and possibly the cornea and the lens.

PMID- 24333674
TI  - Blockade of peripheral P2Y1 receptors prevents the induction of thermal
      hyperalgesia via modulation of TRPV1 expression in carrageenan-induced
      inflammatory pain rats: involvement of p38 MAPK phosphorylation in DRGs.
AB  - Although previous reports have suggested that P2Y1 receptors (P2Y1Rs) are
      involved in cutaneous nociceptive signaling, it remains unclear how P2Y1Rs
      contribute to peripheral sensitization. The current study was designed to
      delineate the role of peripheral P2Y1Rs in pain and to investigate potential
      linkages to mitogen-activated protein kinase (MAPK) in DRGs and Transient
      Receptor Potential Vanilloid 1 (TRPV1) expression in a rodent inflammatory pain
      model. Following injection of 2% carrageenan into the hind paw, expressions of
      P2Y1 and TRPV1 and the phosphorylation rates of both p38 MAPK and ERK but not JNK
      were increased and peaked at day 2 post-injection. Blockade of peripheral P2Y1Rs
      by the P2Y1R antagonist, MRS2500 injection (i.pl, D0 to D2) significantly reduced
      the induction of thermal hyperalgesia, but not mechanical allodynia.
      Simultaneously, MRS2500 injections suppressed upregulated TRPV1 expression and
      DRG p38 phosphorylation, while pERK signaling was not affected. Furthermore,
      inhibition of p38 activation in the DRGs by SB203580 (a p38 inhibitor, i.t, D0 to
      D2) prevented the upregulation of TRPV1 and a single i.t injection of SB203580
      reversed the established thermal hyperalgesia, but not mechanical allodynia.
      Lastly, to identify the mechanism of action of P2Y1Rs, we repeatedly injected the
      P2Y1 agonist, MRS2365 into the naive rat's hind paw and observed a dose-dependent
      increase in TRPV1 expression and p38 MAPK phosphorylation. These data demonstrate
      a sequential role for P2Y1R, p38 MAPK and TRPV1 in inflammation-induced thermal
      hyperalgesia; thus, peripheral P2Y1Rs activation modulates p38 MAPK signaling and
      TRPV1 expression, which ultimately leads to the induction of thermal
      hyperalgesia. 

PMID- 24333675
TI  - Puerarin protected the brain from cerebral ischemia injury via astrocyte
      apoptosis inhibition.
AB  - Puerarin is extensively attractive because of its superior neuroprotective
      effects in stroke prevention. This paper focused on the protective effect of
      puerarin both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was
      operated on male Sprague-Dawley rat for 2 h, different doses of puerarin (2.62,
      7.86 and 23.59 mg/kg) or vehicle were gavaged 1 h after reperfusion. Rats were
      sacrificed after 24 h or 7 days treatment of puerarin/vehicle. In 7.86 and 23.59
      mg/kg groups, infarct volume was reduced (P < 0.05) when puerarin was given once;
      7 days puerarin intervention further reduced the infarct volume (P < 0.05)
      compared with vehicle-treated animal. The modified neurological severity score
      (mNSS) was also raised in day 4 in 7.86 and 23.59 mg/kg groups and in all groups
      in day 7 compared with vehicle (P < 0.05). The number of Nissl body, cleaved
      caspase-3 and GFAP positive cells increased observably after stroke in dose
      dependence in rats. In our in vitro study, we have found that puerarin inhibited
      the pro-apoptosis factor and upregulated the BDNF secret of astrocytes after OGD
      R. This indicated that the repairing effect of puerarin was associated with the
      astrocyte protection. 

PMID- 24333676
TI  - DOR(2)-selective but not DOR(1)-selective antagonist abolishes anxiolytic-like
      effects of the delta opioid receptor agonist KNT-127.
AB  - Recently, we reported that the delta opioid receptor (DOR) agonist KNT-127
      produces anxiolytic-like effects in behaving rats. Here, we report on the roles
      of DOR subtypes ( DOR(1) and DOR(2)) play in mediating KNT-127-induced anxiolytic
      like effects. Pretreatment with the DOR(2)-selective antagonist naltriben (NTB;
      0.05mg/kg, s.c.) completely abolished KNT-127 (3.0mg/kg, s.c.)-induced anxiolytic
      like effects in rats performing the elevated plus-maze task. By contrast, the
      DOR(1)-selective antagonist 7-benzylidenenaltrexone (BNTX; 0.5mg/kg, s.c.)
      produced no effect at a dose that completely blocked the antinociceptive effects
      of KNT-127. These findings were also supported by results from a light/dark test
      and open-field test. We clearly demonstrated that the DOR(2)-selective
      antagonist, but not the DOR(1)-selective antagonist, abolishes the anxiolytic
      like effects of the DOR agonist KNT-127, suggesting different roles of these DOR
      subtypes in anxiety. We propose that DOR(2)-selective agonists would be good
      candidates for future development of anxiolytic drugs.

PMID- 24333677
TI  - Tourmaline combined with Phanerochaete chrysosporium to remediate agricultural
      soil contaminated with PAHs and OCPs.
AB  - The potential application on tourmaline was explored. The combination of
      tourmaline and Phanerochaete chrysosporium was conducted to remediate the field
      soil from the Dagu Drainage River bank of Tianjin in China. The total PAH and OCP
      concentrations in the soil were 6.4+/-0.05 and 145.9+/-1.9mg/kg, respectively.
      During the 60 day remediation program, the remediation degradation rates of all
      the 16 U.S. EPA priority PAHs and OCPs were 53.2+/-4.7% and 43.5+/-3.1%,
      respectively. The PAH and OCP removal rates were 31.9+/-2.9% and 26.4+/-1.8%,
      respectively, in soil with the addition of tourmaline, and the removal rates were
      40.5+/-2.3% and 34.2+/-3.9%, respectively, in soil with the addition of P.
      chrysosporium. Thus, the combination of tourmaline and P. chrysosporium promoted
      the bioremediation rate of PAHs and OCPs in the soil, compared with the rates
      obtained using tourmaline or P. chrysosporium individually for the remediation of
      PAH and OCP degradation. In addition, tourmaline can promote the generation of
      soil hydrogen peroxidase and invertase enzyme, significantly increase the
      indigenous bacterial community and the number of PAH and OCP-degraders compared
      to those in the control, and reduce the soil humic acid content. Hence, the
      present study provides a potential alternative for the remediation of soils
      contaminated by PAHs and OCPs. 

PMID- 24333678
TI  - Synergistic adsorption of heavy metal ions and organic pollutants by
      supramolecular polysaccharide composite materials from cellulose, chitosan and
      crown ether.
AB  - We have developed a simple one-step method to synthesize novel supramolecular
      polysaccharide composites from cellulose (CEL), chitosan (CS) and benzo-15-crown
      5 (B15C5). Butylmethylimidazolium chloride [BMIm(+)Cl(-)], an ionic liquid (IL),
      was used as a sole solvent for dissolution and preparation of the composites.
      Since majority of [BMIm(+)Cl(-)] used was recovered for reuse, the method is
      recyclable. The [CEL/CS+B15C5] composites obtained retain properties of their
      components, namely superior mechanical strength (from CEL), excellent adsorption
      capability for heavy metal ions and organic pollutants (from B15C5 and CS). More
      importantly, the [CEL/CS+B15C5] composites exhibit truly supramolecular
      properties. By itself CS, CEL and B15C5 can effectively adsorb Cd(2+), Zn(2+) and
      2,4,5-trichlorophenol. However, adsorption capability of the composite was
      substantially and synergistically enhanced by adding B15C5 to either CEL and/or
      CS. That is, the adsorption capacity (qe values) for Cd(2+) and Zn(2+) by
      [CS+B15C5], [CEL+B15C5] and [CEL+CS+B15C5] composites are much higher than
      combined qe values of individual CS, CEL and B15C5 composites. It seems that
      B15C5 synergistically interact with CS (or CEL) to form more stable complexes
      with Cd(2+) (or Zn(2+)), and as a consequence, the [CS+B15C5] (or the
      [CEL+B15C5]) composite can adsorb relatively larger amount Cd(2+) (or Zn(2+)).
      Moreover, the pollutants adsorbed on the composites can be quantitatively
      desorbed to enable the [CS+CEL+B15C5] composites to be reused with similar
      adsorption efficiency. 

PMID- 24333679
TI  - Heading for an economic industrial upgrading of crude glycerol from biodiesel
      production to 1,3-propanediol by Lactobacillus diolivorans.
AB  - Lactobacillus diolivorans was evaluated as a potential organism for production of
      1,3-propanediol under industrially relevant conditions. Crude glycerol of
      different origins has been tested and showed no inhibitory effects on growth or
      production. Using crude glycerol from biodiesel production from palm oil 85 g/l
      1,3-propanediol have been obtained with a productivity of 0.45 g/lh in a fed
      batch cultivation. Sugar necessary for the formation of biomass was replaced with
      a hydrolysate from lignocellulosic material resulting in 75 g/l 1,3-propanediol
      and a productivity of 0.36 g/lh. Lignocellulosic hydrolysate contained the
      potential inhibitors furfural and 5-hydroxymethylfurfural at concentrations of
      0.7 and 0.3 g/l, respectively. Addition of furfural and 5-hydroxymethylfurfural
      to batch cultures in said concentrations did not show inhibitory effects on
      growth or 1,3-propanediol production.

PMID- 24333680
TI  - Molecular comparative assessment of the microbial ecosystem in rumen and faeces
      of goats fed alfalfa hay alone or combined with oats.
AB  - The objective of this work was to compare the biomass and community structure of
      bacteria, protozoa and archaea communities in samples of rumen and faeces of
      goats and to what extent the diet (alfalfa hay with or without supplemented oats)
      offered to them exert an influence. Four cannulated adult goats fistulated in the
      rumen were used in a cross over design experiment in two experimental periods of
      26 days, consisting in 14 days of adaptation, 7 days of sampling rumen contents
      and 5 days of digestibility measurement. Bacterial, protozoa and archaeal biomass
      and the communities' structure was assessed by real time PCR (qPCR) and
      denaturing gradient gel electrophoresis (DGGE), respectively. The numbers of
      archaea and bacteria in both rumen and faeces were higher and lower,
      respectively, in animals fed AH diet (P < 0.005). Contrary, protozoal numbers
      were not affected by the diet but were lower (P < 0.001) in faeces than in rumen.
      The analysis of the community structure revealed a consistently different
      population in structure in rumen and faeces for the three studied microbial
      groups and that supplementing alfalfa hay with oats led to a decrease in the
      similarity between sites in the rumen and faeces: similarity indexes for bacteria
      (57 and 27%), archaea (26 and 9%) and protozoa (62 and 22%) in animals fed AH and
      AHO diets, respectively. 

PMID- 24333681
TI  - A P2 and P3 substrate specificity comparison between the Murray Valley
      encephalitis and West Nile virus NS2B/NS3 protease using C-terminal agmatine
      dipeptides.
AB  - The Murray Valley encephalitis virus (MVEV) and the West Nile virus (WNV) are
      mosquito-borne single-stranded RNA Flaviviruses responsible for many cases of
      viral encephalitis and deaths worldwide. The former is endemic in north Australia
      and Papua New Guinea while the latter has spread to different parts of the world
      and was responsible for a recent North American outbreak in 2012, resulting in
      243 fatalities. There is currently no approved vaccines or drugs against MVEV and
      WNV viral infections. A plausible drug target is the viral non-structural
      NS2B/NS3 protease due to its role in viral replication. This trypsin-like serine
      protease recognizes and cleaves viral polyproteins at the C-terminal end of an
      arginine residue, opening an avenue for the development of peptide-based
      antivirals. This communication compares the P2 and P3 residue preferences of the
      MVEV and WNV NS2B/NS3 proteases using a series of C-terminal agmatine dipeptides.
      Our results revealed that both viral enzymes were highly specific toward lysines
      at the P2 and P3 positions, suggesting that a peptidomimetic viral protease
      inhibitor developed against one virus should also be active against the other. 

PMID- 24333682
TI  - Conformation of the critical pH sensitive region of troponin depends upon a
      single residue in troponin I.
AB  - The calcium sensitivity of cardiac and skeletal muscle is reduced during
      cytosolic acidosis, and this inhibition is more pronounced in cardiac muscle.
      Replacing cardiac troponin I with skeletal troponin I reduces the pH sensitivity
      of cardiac muscle. This diminished pH sensitivity depends on a single amino acid
      difference in troponin I: an alanine in cardiac and a histidine in skeletal.
      Studies suggested that when this histidine is protonated, it forms an
      electrostatic interaction with glutamate 19 on the surface of cardiac troponin C.
      Structures of the skeletal and cardiac troponin complexes show very different
      conformations for the region of troponin I surrounding this residue. In this
      study, we determined the structure of skeletal troponin I bound to cardiac
      troponin C. Skeletal troponin I is found to bind to cardiac troponin C with
      histidine 130 in close proximity to glutamate 19. This conformation is homologous
      to the crystal structure of the skeletal troponin complex; but different than in
      the cardiac complex. We show that an A162H variant of cardiac troponin I adopts a
      conformation similar to the skeletal structure. The implications of these
      structural differences in the context of cardiac muscle regulation are discussed.

PMID- 24333683
TI  - Biochemical characterization of the maize cytokinin dehydrogenase family and
      cytokinin profiling in developing maize plantlets in relation to the expression
      of cytokinin dehydrogenase genes.
AB  - The cytokinin dehydrogenases (CKX; EC 1.5.99.12) are a protein family that
      maintains the endogenous levels of cytokinins in plants by catalyzing their
      oxidative degradation. The CKX family in maize (Zea mays L.) has thirteen
      members, only two of which--ZmCKX1 and ZmCKX10--have previously been
      characterized in detail. In this study, nine further maize CKX isoforms were
      heterologously expressed in Escherichia coli, purified by affinity and ion
      exchange chromatography and biochemically characterized. ZmCKX6 and ZmCKX9 could
      only be expressed successfully after the removal of putative sequence-specific
      vacuolar sorting signals (LLPT and LPTS, respectively), suggesting that these
      proteins are localized to the vacuole. Substrate specificity analyses revealed
      that the CKX isoforms can be grouped into two subfamilies: members of the first
      strongly prefer cytokinin free bases while members of the second degrade a broad
      range of substrates. The most active isoform was found to be ZmCKX1. One of the
      studied isoforms, ZmCKX6, seemed to encode a nonfunctional enzyme due to a
      mutation in a conserved HFG protein domain at the C-terminus. Site-directed
      mutagenesis experiments revealed that this domain is essential for CKX activity.
      The roles of the maize CKX enzymes in the development of maize seedlings during
      the two weeks immediately after radicle emergence were also investigated. It
      appears that ZmCKX1 is a key regulator of active cytokinin levels in developing
      maize roots. However, the expression of individual CKX isoforms in the shoots
      varied and none of them seemed to have strong effects on the cytokinin pool.

PMID- 24333684
TI  - Isolation and functional characterization of the ShCBF1 gene encoding a CRT/DRE
      binding factor from the wild tomato species Solanum habrochaites.
AB  - Plant growth and productivity are greatly affected by low ambient temperature.
      Complex cascades of gene expression in cold stress response are regulated by
      transcription factors. In this study, a cDNA clone, named ShCBF1, was isolated
      from Solanum habrochaites seedlings (a wild relative of cultivated tomato). It
      was classified as one of CBF family members based on multiple sequence alignment.
      The expression analysis confirmed that ShCBF1 was induced by low temperature,
      high salinity and drought stress. Experiments of subcellular localization in
      tobacco leaf cells indicated that it was localized in nucleus. Transient
      expression assay using onion epidermal cells revealed that the ShCBF1 protein
      could function similarly to AtCBF1 in activating the expression of reporter genes
      with a CRT/DRE element in their promoter. Moreover, ectopic overexpression of
      ShCBF1 in Arabidopsis enhanced freezing and high salinity tolerance of transgenic
      plants by improving the expression levels of some stress-responsive marker genes.
      Taken together, our results suggest that ShCBF1 behaves as a typical plant CBF
      transcription factor and might be involved in plant response to various
      environmental stresses. 

PMID- 24333685
TI  - Function of an anti-lipopolysaccharide factor (ALF) isoform isolated from the
      hemocytes of the giant freshwater prawn Macrobrachium rosenbergii in protecting
      against bacterial infection.
AB  - In this study, a 780-bp full-length cDNA encoding Macrobrachium rosenbergii anti
      lipopolysaccharide factor (MrALF) from hemocytes was cloned and identified. The
      ALF isoform exhibited immune activities, and its concentration in hemolymph was
      determined. An in vivo expression study showed that the ALF mRNA level of
      hemocytes could be induced by lipopolysaccharides (LPSs) in an exposure time
      dependent manner. Purified recombinant MrALF (rMrALF) expressed in the yeast
      Pichia pastoris SMD1168 eukaryotic protein expression system demonstrated
      antibacterial activity against the Gram-negative prawn pathogen Aeromonas
      hydrophila (minimum inhibitory concentration (MIC)=0.806MUM, minimum bactericidal
      concentration (MBC)=1.606MUM) but not the Gram-positive pathogen Lactococcus
      garvieae exposed to 25.696MUM of rALF. However, rMrALF can bind to Gram-negative
      and -positive bacteria. An in vivo expression study demonstrated that the ALF
      concentrations in prawn hemocytes and plasma were 0.176MUM and 0.168MUM,
      respectively; following LPS treatment for 6h, the corresponding concentrations
      were 0.133MUM in hemocytes and 0.272MUM in plasma. Furthermore, the percentage of
      hemocytes phagocytosing bacteria cells was higher in hemoyctes previously treated
      with MrALF than those treated with sterile medium. These results suggest that in
      the innate immune response of M. rosenbergii, the MrALF from hemocytes may play
      an opsonin during a bacterial invasion. 

PMID- 24333686
TI  - Development of a multiplex real-time PCR assay for the detection of Bordetella
      pertussis and Bordetella parapertussis in a single tube reaction.
AB  - Pertussis is an infectious respiratory disease caused by the fastidious bacterium
      Bordetella pertussis, which may infect unvaccinated, previously vaccinated
      children, and adults in whom immunity has waned. Infants are at a particular risk
      for severe disease and complications. Bordetella parapertussis may cause a
      similar illness, however the symptoms are less severe and of shorter duration.
      Pertussis is a highly contagious disease and early diagnosis is essential.
      Studies have shown that PCR is 2-4 times more likely than culture to detect
      Bordetella pertussis. We developed a multiplex, real-time PCR assay using analyte
      specific reagent (ASR) primers and probes dispensed in a convenient lyophilized
      bead format that targeted the multi-copy insertion sequences IS481 and IS1001 of
      B. pertussis and B. parapertussis, respectively. These specific ASRs were used in
      conjunction with Cepheid Smartmix. Included in the ASRs is a competitive internal
      control to evaluate the performance of the PCR reaction. After DNA extraction,
      amplification and detection were done on the Smart Cycler System, which performs
      integrated amplification and detection automatically in a single step.
      Specificity of the assay was confirmed using multiple distinct bacterial strains.
      Sensitivity of the assay and extraction efficiency were evaluated on DNA isolated
      from pure bacterial cultures and on spiked respiratory specimens. We also spiked
      different swab types and transport media to evaluate for interfering substances.
      To assess accuracy, we studied different patient specimen types received from two
      outside laboratories that used similar or different methods to detect B.
      pertussis and B. parapertussis. The sensitivity and the specificity of the assay
      for B. pertussis were 90% and 96%, respectively, and for B. parapertussis 71%
      (only 7 positive specimens were available for testing) and 100%, respectively.
      Our assay was found to be a valid method for the simultaneous detection of B.
      pertussis and B. parapertussis. 

PMID- 24333687
TI  - Proinflammatory effects and oxidative stress within human bronchial epithelial
      cells exposed to atmospheric particulate matter (PM(2.5) and PM(>2.5)) collected
      from Cotonou, Benin.
AB  - After particulate matter (PM) collection in Cotonou (Benin), a complete
      physicochemical characterization of PM2.5 and PM>2.5 was led. Then, their adverse
      health effects were evaluated by using in vitro culture of human lung cells. BEAS
      2B (bronchial epithelial cells) were intoxicated during short-term exposure at
      increasing PM concentrations (1.5-96 MUg/cm(2)) to determine global cytotoxicity.
      Hence, cells were exposed to 3 and 12 MUg/cm(2) to investigate the potential
      biological imbalance generated by PM toxicity. Our findings showed the ability of
      both PM to induce oxidative stress and to cause inflammatory cytokines/chemokines
      gene expression and secretion. Furthermore, PM were able to induce gene
      expression of enzymes involved in the xenobiotic metabolism pathway. Strong
      correlations between gene expression of metabolizing enzymes, proinflammatory
      responses and cell cycle alteration were found, as well as between
      proinflammatory responses and cell viability. Stress oxidant parameters were
      highly correlated with expression and protein secretion of inflammatory
      mediators. 

PMID- 24333688
TI  - Potential therapeutic effects of functionally active compounds isolated from
      garlic.
AB  - The medicinal properties of functionally active organosulfur compounds such as
      allin, diallyl disulfide, S-allylmercaptocysteine, and S-trityl-L-cysteine
      isolated from garlic have received great attention from a large number of
      investigators who have studied their pharmacological effects for the treatment of
      various diseases. These organosulfur compounds are able to prevent for
      development of cancer, cardiovascular, neurological, and liver diseases as well
      as allergy and arthritis. There have been also many reports on toxicities and
      pharmacokinetics of these compounds. The aim of this study is to review a variety
      of experimental and clinical reports, and describe the effectiveness, toxicities
      and pharmacokinetics, and possible mechanisms of pharmaceutical actions of
      functionally active compounds isolated from garlic.

PMID- 24333689
TI  - Toxicity generated through inhibition of pyruvate carboxylase and carnitine
      palmitoyl transferase-1 is similar to high glucose/palmitate-induced
      glucolipotoxicity in INS-1 beta cells.
AB  - This work was initiated to determine whether toxicity generated through
      inhibition of mitochondrial fuel metabolism is similar to high glucose/palmitate
      (HG/PA)-induced glucolipotoxicity. Influx of glucose and free fatty acids into
      the tricarboxylic acid (TCA) cycle was inhibited by treatment with the pyruvate
      carboxylase (PC) inhibitor phenylacetic acid (PAA) and carnitine palmitoyl
      transferase-1 (CPT-1) inhibitor etomoxir (Eto), or knockdown of PC and CPT-1.
      Treatment of PAA/Eto or knockdown of PC/CPT-1 induced apoptotic death in INS-1
      beta cells. Similar to HG/PA treatment, PAA/Eto increased endoplasmic reticulum
      stress responses but decreased the Akt signal. JNK inhibitor or chemical
      chaperone was protective against both PAA/Eto- and HG/PA-induced cell death. All
      attempts to reduce [Ca2+](i), stimulate lipid metabolism, and increase the TCA
      cycle intermediate pool protected PAA/Eto-induced death as well as HG/PA-induced
      death. These data suggest that signals induced from impaired mitochondrial fuel
      metabolism play a critical role in HG/PA-induced glucolipotoxicity.

PMID- 24333690
TI  - In vivo genotoxicity of a novel heterocyclic amine, aminobenzoazepinoquinolinone
      derivative (ABAQ), produced by the Maillard reaction between glucose and l
      tryptophan.
AB  - We recently demonstrated that a novel heterocyclic amine, 5-amino-6-hydroxy-8H
      benzo[6,7]azepino[5,4,3-de]quinolin-7-one (ABAQ), is produced from glucose and l
      tryptophan by the Maillard reaction at physiological temperature and pH, and that
      ABAQ was strongly mutagenic for Salmonella strains in the presence of S9 mix.
      Here, we present the results of three in vivo genotoxicity assays of ABAQ. The
      comet assay revealed that DNA damage was significantly increased in the livers,
      kidneys, lungs, and bone marrows of ICR mice, 3h after i.p. injection of ABAQ
      (50mg/kg body weight (bw)). To evaluate clastogenicity, the peripheral blood
      micronucleus test was performed, also in ICR mice. ABAQ induced micronucleated
      reticulocytes (MNRETs) in a dose-dependent manner; the frequency of MNRETs was
      significantly elevated at all i.p. doses (12.5, 25, and 50mg/kg bw) after 48h. To
      investigate the mutagenicity of ABAQ in vivo, gpt delta transgenic mice were
      treated with five consecutive administrations of ABAQ by gavage at doses of 25 or
      50mg/kg per week for 3 weeks. The frequencies of gpt mutations (MF) in the liver
      of mice increased significantly compared with controls, in a dose-dependent
      manner. No significant increase of gpt MF was detected in the kidneys. Base
      substitutions predominated; both G:C->A:T and A:T->C:G mutations were
      significantly increased by ABAQ. The Spi(-) MF was also significantly increased
      in the liver after ABAQ treatment. If formed in vivo, ABAQ may give rise to
      adverse genotoxic effects. 

PMID- 24333691
TI  - A mitochondrial location for haemoglobins--dynamic distribution in ageing and
      Parkinson's disease.
AB  - Haemoglobins are iron-containing proteins that transport oxygen in the blood of
      most vertebrates. The mitochondrion is the cellular organelle which consumes
      oxygen in order to synthesise ATP. Mitochondrial dysfunction is implicated in
      neurodegeneration and ageing. We find that alpha and beta haemoglobin (Hba and
      Hbb) proteins are altered in their distribution in mitochondrial fractions from
      degenerating brain. We demonstrate that both Hba and Hbb are co-localised with
      the mitochondrion in mammalian brain. The precise localisation of the Hbs is
      within the inner membrane space and associated with inner mitochondrial membrane.
      Relative mitochondrial to cytoplasmic ratios of Hba and Hbb show changing
      distributions of these proteins during the process of neurodegeneration in the
      pcd(5j) mouse brain. A significant difference in mitochondrial Hba and Hbb
      content in the mitochondrial fraction is seen at 31 days after birth, this
      corresponds to a stage when dynamic neuronal loss is measured to be greatest in
      the Purkinje Cell Degeneration mouse. We also report changes in mitochondrial Hba
      and Hbb levels in ageing brain and muscle. Significant differences in
      mitochondrial Hba and Hbb can be seen when comparing aged brain to muscle,
      suggesting tissue specific functions of these proteins in the mitochondrion. In
      muscle there are significant differences between Hba levels in old and young
      mitochondria. To understand whether the changes detected in mitochondrial Hbs are
      of clinical significance, we examined Parkinson's disease brain,
      immunohistochemistry studies suggest that cell bodies in the substantia nigra
      accumulate mitochondrial Hb. However, western blotting of mitochondrial fractions
      from PD and control brains indicates significantly less Hb in PD brain
      mitochondria. One explanation could be a specific loss of cells containing
      mitochondria loaded with Hb proteins. Our study opens the door to an examination
      of the role of Hb function, within the context of the mitochondrion-in health and
      disease.

PMID- 24333693
TI  - MiR-139-5p inhibits HGTD-P and regulates neuronal apoptosis induced by hypoxia
      ischemia in neonatal rats.
AB  - Human growth transformation dependent protein (HGTD-P) is a newly identified
      protein that promotes neuronal apoptosis in hypoxia-ischemia brain damage (HIBD)
      in neonatal rats. However, the mechanisms regulating HGTD-P expression are not
      clear. Here we describe microRNAs targeted to HGTD-P and examine their effects on
      regulating neuronal apoptosis in HIBD. We use samples from cultured neurons after
      oxygen-glucose deprivation (OGD) and postnatal day 10 rat brains after hypoxia
      ischemia (HI). RT-PCR, Western blotting, and immunostaining are used to detect
      the expression of HGTD-P and cleaved caspase 3, as well as real-time PCR detects
      microRNA expression. MicroRNA agomir is used to inhibit the expression of HGTD-P,
      and DAPI, TUNEL, and TTC staining are employed to detect cell apoptosis and brain
      damage. Moreover, in vitro processing assay is used to examine the mechanism by
      which HI down-regulates miR-139-5p expression. We found that miR-139-5p is down
      regulated in neurons and rat brains after HI treatment. The expression pattern of
      miR-139-5p correlates inversely with that of HGTD-P. Furthermore, miR-139-5p
      agomir inhibits neuronal apoptosis and attenuates HIBD, which is concurrent with
      down-regulation of HGTD-P. Moreover, pre-miR-139 processing activity decreases in
      extracts from OGD neurons, and OGD neuronal extracts attenuates the processing of
      pre-miR-139 by Dicer. In conclusion, HI induces inhibitors which block the
      processing step of pre-miR-139, resulting in the down-regulation of mature miR
      139-5p. The down-regulation of miR-139-5p plays a critical role in the up
      regulation of HGTD-P expression. MiR-139-5p agomir attenuates brain damage when
      used 12h after HI, providing a longer therapeutic window than anti-apoptosis
      compounds currently available. 

PMID- 24333694
TI  - Cortistatin attenuates inflammatory pain via spinal and peripheral actions.
AB  - Clinical pain, as a consequence of inflammation or injury of peripheral organs
      (inflammatory pain) or nerve injury (neuropathic pain), represents a serious
      public health issue. Treatment of pain-related suffering requires knowledge of
      how pain signals are initially interpreted and subsequently transmitted and
      perpetuated. To limit duration and intensity of pain, inhibitory signals
      participate in pain perception. Cortistatin is a cyclic-neuropeptide that exerts
      potent inhibitory actions on cortical neurons and immune cells. Here, we found
      that cortistatin is a natural analgesic component of the peripheral nociceptive
      system produced by peptidergic nociceptive neurons of the dorsal root ganglia in
      response to inflammatory and noxious stimuli. Moreover, cortistatin is produced
      by GABAergic interneurons of deep layers of dorsal horn of spinal cord. By using
      cortistatin-deficient mice, we demonstrated that endogenous cortistatin
      critically tunes pain perception in physiological and pathological states.
      Furthermore, peripheral and spinal injection of cortistatin potently reduced
      nocifensive behavior, heat hyperalgesia and tactile allodynia in experimental
      models of clinical pain evoked by chronic inflammation, surgery and arthritis.
      The analgesic effects of cortistatin were independent of its anti-inflammatory
      activity and directly exerted on peripheral and central nociceptive terminals via
      Galphai-coupled somatostatin-receptors (mainly sstr2) and blocking intracellular
      signaling that drives neuronal plasticity including protein kinase A-, calcium-
      and Akt/ERK-mediated release of nociceptive peptides. Moreover, cortistatin could
      modulate, through its binding to ghrelin-receptor (GHSR1), pain-induced
      sensitization of secondary neurons in spinal cord. Therefore, cortistatin emerges
      as an anti-inflammatory factor with potent analgesic effects that offers a new
      approach to clinical pain therapy, especially in inflammatory states. 

PMID- 24333695
TI  - Motor cognition-motor semantics: action perception theory of cognition and
      communication.
AB  - A new perspective on cognition views cortical cell assemblies linking together
      knowledge about actions and perceptions not only as the vehicles of integrated
      action and perception processing but, furthermore, as a brain basis for a wide
      range of higher cortical functions, including attention, meaning and concepts,
      sequences, goals and intentions, and even communicative social interaction. This
      article explains mechanisms relevant to mechanistic action perception theory,
      points to concrete neuronal circuits in brains along with artificial neuronal
      network simulations, and summarizes recent brain imaging and other experimental
      data documenting the role of action perception circuits in cognition, language
      and communication. 

PMID- 24333692
TI  - Mitochondrial and postmitochondrial survival signaling in cancer.
AB  - Cancer cells are resistant to conventional chemotherapy and radiotherapy,
      however, the molecular mechanisms of resistance to therapy remain unclear.
      Cellular survival machinery protects mitochondrial integrity against endogenous
      or exogenous stresses. Prodeath molecules orchestrate around mitochondria to
      initiate and execute cell death in cancer, and also play an underappreciated role
      in survival of cancer cells. Prosurvival mechanisms can operate at mitochondrial
      and postmitochondrial levels to attenuate core apoptotic death program. It is
      intriguing to explore how prosurvival and prodeath molecules crosstalk to
      regulate mitochondrial functions leading to increased cancer cell survival. This
      review describes some putative survival mechanisms at mitochondria, which may
      play a role in designing effective agents for cancer prevention and therapy.
      These survival pathways may also have significance in understanding other human
      pathophysiological conditions including diabetes, cardiovascular, autoimmune, and
      neurodegenerative diseases. 

PMID- 24333696
TI  - Endothelial LGALS9 splice variant expression in endothelial cell biology and
      angiogenesis.
AB  - Galectins are carbohydrate binding proteins with versatile functions in tumor
      progression. Galectin-9, encoded by LGALS9, has been associated with metastasis
      and immunosuppression. We previously reported on regulation of LGALS9 expression
      during endothelial cell activation. Here, we show increased galectin-9 protein
      levels in the endothelium of different tumors, including carcinomas of the lung,
      liver, breast and kidney. Endothelial cells were found to express five LGALS9
      splice variants, two of which have not been reported before. Splicing was found
      to be confined to exons 5, 6 and 10. Transfection of human microvascular
      endothelial cells (HMEC) with galectin-9?5, a specific LGALS9 splice variant,
      induced a small but significant increase of proliferation, while migration was
      not affected by any LGALS9 splice variant. Application of recombinant galectin
      9?5 protein dose-dependently reduced proliferation and migration of HMEC as well
      as human umbilical vein endothelial cells in vitro. Enhanced sprouting and
      migration of human umbilical vein endothelial cell (HUVEC) towards a galectin-9?5
      gradient were observed. Interestingly, galectin-9?5 was found to induce a small
      inhibitory effect on angiogenesis in vivo. Collectively, these data show that
      endothelial cells regulate the expression and splicing of LGALS9 during
      angiogenesis. The function of the dominant splice variant, i.e. galectin-9?5, in
      endothelial cell biology depends on the concentration and environmental context
      in which it is presented to the cells. 

PMID- 24333697
TI  - Enzymatic saccharification of pretreated wheat straw: comparison of solids
      recycling, sequential hydrolysis and batch hydrolysis.
AB  - In the enzymatic hydrolysis of lignocellulose materials, the recycling of the
      solid residue has previously been considered within the context of enzyme
      recycling. In this study, a steady state investigation of a solids-recycling
      process was made with pretreated wheat straw and compared to sequential and batch
      hydrolysis at constant reaction times, substrate feed and liquid and enzyme
      consumption. Compared to batch hydrolysis, the recycling and sequential processes
      showed roughly equal hydrolysis yields, while the volumetric productivity was
      significantly increased. In the 72h process the improvement was 90% due to an
      increased reaction consistency, while the solids feed was 16% of the total
      process constituents. The improvement resulted primarily from product removal,
      which was equally efficient in solids-recycling and sequential hydrolysis
      processes. No evidence of accumulation of enzymes beyond the accumulation of the
      substrate was found in recycling. A mathematical model of solids-recycling was
      constructed, based on a geometrical series. 

PMID- 24333698
TI  - Efficient production of l-lactic acid using co-feeding strategy based on cane
      molasses/glucose carbon sources.
AB  - L-Lactic acid is an important platform chemical, which ought to be produced under
      cost control to meet its huge demand. Cane molasses, a waste from sugar
      manufacturing processes, is hopeful to be utilized as a cheap carbon source for L
      lactic acid fermentation. Considering that cane molasses contains nutrients and
      hazardous substances, efficient production of L-lactic acid was developed by
      using a co-feeding strategy based on the utilization of cane molasses/glucose
      carbon sources. Based on the medium optimization with response surface method,
      168.3g/L L-lactic acid was obtained by a Bacillus coagulans strain H-1 after 78h
      fed-batch fermentation, with a productivity of 2.1g/Lh and a yield of 0.88g/g.
      Since cane molasses is a feasible carbon source, the co-feeding fermentation
      might be a promising alternative for the economical production of L-lactic acid.

PMID- 24333699
TI  - Unprecedented development of anammox in presence of organic carbon using seed
      biomass from a tannery Common Effluent Treatment Plant (CETP).
AB  - This work describes development of a microbial consortium dominant in anammox in
      presence of organic carbon (available through cell lyses) by employing simple
      sequencing batch operation in 23 cycles exceeding 400days. Seed biomass from a
      tannery Common Effluent Treatment Plant (CETP) was enriched for anammox and
      attained maximum removals of NH4-N (95%) and NO2-N (98%). The anammox was
      confirmed by nitrogen mass balance in a controlled batch experiment and by DNA
      extraction-PCR-agarose gel electrophoresis. The effective anammox followed first
      order reaction kinetics with rate constant of 0.0141/h and half-saturation
      constant of 10.6mg/L. Evidence for coexistence of denitrification (99% NO2-N
      removal) and anammox (57.8% NH4-N removal) was demonstrated. This study opens-up
      possible application of microbial consortium dominant in anammox for simultaneous
      removal of ammonia and organic carbon from wastewaters. 

PMID- 24333700
TI  - The robustness of ANAMMOX process under the transient oxytetracycline (OTC)
      shock.
AB  - The effect of transient oxytetracycline (OTC) shock on the stability of anaerobic
      ammonium oxidation (ANAMMOX) process was evaluated in the present study. The
      shock test was implemented with 155-1731mgL(-1) OTC, lasting for 1 to 3-fold
      hydraulic retention times, under the nitrogen loading rate (NLR) of 6.72 and
      13.4kgm(-3)d(-1). The response of the process was divided into shock and recovery
      stage and the performance under the stress was indicated by stability index and
      granule characteristic. In the shock period, nitrogen removal rate (NRR) was
      ranged from 12.1 to 12.1-4.04kgm(-3)d(-1). The specific ANAMMOX activity (SAA)
      and heme c content, were respectively reduced by 1.4% and 17.6-29.4%. Foremost,
      the OTC shock was restorable and the recovery lasted for 4-353h. The robustness
      of ANAMMOX process was dependent on OTC level, duration of shock and NLR applied.

PMID- 24333701
TI  - Bioethanol production from the nutrient stress-induced microalga Chlorella
      vulgaris by enzymatic hydrolysis and immobilized yeast fermentation.
AB  - The microalga Chlorella vulgaris is a potential feedstock for bioenergy due to
      its rapid growth, carbon dioxide fixation efficiency, and high accumulation of
      lipids and carbohydrates. In particular, the carbohydrates in microalgae make
      them a candidate for bioethanol feedstock. In this study, nutrient stress
      cultivation was employed to enhance the carbohydrate content of C. vulgaris.
      Nitrogen limitation increased the carbohydrate content to 22.4% from the normal
      content of 16.0% on dry weight basis. In addition, several pretreatment methods
      and enzymes were investigated to increase saccharification yields. Bead-beating
      pretreatment increased hydrolysis by 25% compared with the processes lacking
      pretreatment. In the enzymatic hydrolysis process, the pectinase enzyme group was
      superior for releasing fermentable sugars from carbohydrates in microalgae. In
      particular, pectinase from Aspergillus aculeatus displayed a 79% saccharification
      yield after 72h at 50 degrees C. Using continuous immobilized yeast fermentation,
      microalgal hydrolysate was converted into ethanol at a yield of 89%. 

PMID- 24333702
TI  - New triterpene saponins from the roots of Glycyrrhiza yunnanensis and their rapid
      screening by LC/MS/MS.
AB  - The roots of Glycyrrhiza yunnanensis Cheng f. et L. K. Dai ex P. C. Li are used
      as licorice in traditional medicine of Southwest China. Triterpene saponins are
      the major chemical constituents. In this study, one new oleanane-type
      triterpenoid, glyyunnansapogenin I (I), seven new triterpene saponins,
      yunganosides E3 (II), L (III), M (IV), N1 (V), O (VI), P (VII) and N2 (VIII),
      together with four known saponins (IX-XII) were isolated from the roots of G.
      yunnanensis by preparative chromatography. Their structures were identified by
      spectroscopic analysis including NMR and HR-MS. Based on (-)-ESI-MS/MS
      fragmentation behaviors of these reference standards, an LC/MS/MS method using
      neutral loss scan and precursor ion scan on a triple quadrupole mass spectrometer
      was established to rapidly and comprehensively analyze triterpene saponins in G.
      yunnanensis. Combined with high-accuracy qTOF mass spectrometry analysis, a total
      of 50 saponins were detected, and their structures were identified or tentatively
      characterized. This is the first systematic study on triterpene saponins in G.
      yunnanensis. 

PMID- 24333703
TI  - Isolation, identification and characterization of novel process-related
      impurities in flupirtine maleate.
AB  - Flupirtine maleate is a centrally acting, non-opioid, nonsteroidal
      antiinflammatory analgesic. During the manufacturing of flupirtine maleate, two
      unknown impurities present in the laboratory batches in the range of 0.05-1.0%
      along with the known impurities in HPLC analysis. These unknown impurities were
      obtained from the enriched mother liquor by column chromatography. Based on the
      complete spectral analysis (MS, (1)H, (13)C, 2D NMR and IR) and knowledge of the
      synthetic scheme of flupirtine maleate, these two new impurities were designated
      as diethyl 5-((4-fluorobenzyl)amino)-2-oxo-1H-imidazo[4,5-b]pyridine-1,3(2H)
      dicarboxylate (impurity-I) and diethyl(6-((4-fluorobenzyl)amino)pyridine-2,3
      diyl)dicarbamate (impurity-II). Impurity isolation, identification, structure
      elucidation and the formation of impurities were also discussed. Preparation and
      structure elucidation of impurity-III were also first reported in this paper. 

PMID- 24333704
TI  - Development and validation of an indirect pulsed electrochemical detection method
      for monitoring the inhibition of Abl1 tyrosine kinase.
AB  - A new method for monitoring the enzyme inhibition of Abl1 tyrosine kinase by
      liquid chromatography-indirect pulsed electrochemical detection (LC-InPED) was
      developed. In this method, adsorption of a peptide analyte at the noble metal
      electrode suppresses the oxidation of polyols under alkaline condition to elicit
      an indirect response resulting in a negative peak of the target peptide. Among
      the reagents tested, D-gluconic acid sodium salt gave the best overall signal to
      noise (S/N) values for the indirect detection of p-Abltide, the product of Abl1
      enzymatic reaction. 50 MUM D-gluconic acid sodium salt dissolved in a mixture of
      78% water-22% acetonitrile-0.03% trifluoroacetic acid (TFA) was used as the
      mobile phase. Chromatographic separation was achieved on an Alltima C18 (I.D. 5
      MUm; 250 mm * 4.6 mm) column with the mobile phase flow rate of 0.5 ml/min. 0.5M
      sodium hydroxide was added post-column to maintain alkaline conditions in the PED
      cell. The limit of quantification (LOQ) was 0.2 MUM for p-Abltide, which was
      about 50-fold lower than direct PED analysis. The residual plot of the linear
      calibration curve indicated a good fit with a linear model within the
      investigated concentration range of p-Abltide. Intra- and inter-day precision was
      not more than 6.5% and accuracy was from -5.75% to +1.54%. The validated LC-InPED
      method was successfully applied for monitoring of p-Abltide in Abl1 enzyme
      reaction and the inhibition study of Abl1. The determined IC50 values of model
      inhibitors, imatinib, nilotinib and dasatinib, were 601.4 nM (R(2)=0.99), 32.3 nM
      (R(2)=0.99) and 1.3 nM (R(2)=0.98), respectively. These results were consistent
      with literature data. To the best of our knowledge this is the first time a LC
      InPED method has been used to monitor an enzyme reaction.

PMID- 24333705
TI  - Monitoring of four dipyrone metabolites in communal wastewater by solid phase
      extraction liquid chromatography electrospray ionization quadrupole time-of
      flight mass spectrometry.
AB  - Liquid chromatography quadrupole time-of-flight spectrometry (LC-Q-TOF-MS),
      equipped with electrospray ionization (ESI), was developed for the determination
      of the main metabolites of dipyrone - 4-aminoantipyrine (4-AA), 4
      acetylaminoantipyrine (4-AAA), 4-formylaminoantipyrine (4-FAA) and 4
      methylaminoantipyrine (4-MAA) in communal wastewater after reversed-phase solid
      phase extraction (SPE) in the low to several MUg/l concentration range. Samples
      originated from conventional wastewater treatment plant (WWTP) using activated
      sewage sludge as well as from a pilot-scale WWTP operating in mixed mode
      (activated sewage sludge and cascade biofilms reactors with biofilms growing on
      fix beds and roots of greenhouse plants). Results of the present study confirmed
      the outcomes of our previous report according to which, 4-FAA was the most
      persistent metabolite, while 4-AAA and 4-MAA could be determined in the highest
      and lowest concentration, respectively. Moreover, the study of intraday variation
      of the concentration of these metabolites revealed that the concentration of 4
      AA, 4-AAA and 4-FAA registered a 46%-75% increase in the samples collected at
      noon compared to those collected at 6 AM. Chlorination did not affect
      considerably the removal efficiency (about 15%) of these metabolites in samples
      collected for 3 months consecutively before and after disinfection. Both
      wastewater treatment techniques efficiently removed 4-AAA (between 80 and 96%).
      However, in the summer season, the removal efficiency of conventional WWTP using
      open-air aerated tanks is lower by 30%, (on average) than in the cold season. The
      concentration of the investigated metabolites showed increased concentrations in
      the winter season confirming the intake habits of the population from this
      popular analgesic and antipyretic drug. 

PMID- 24333706
TI  - Application of independent component analysis on Raman images of a pharmaceutical
      drug product: pure spectra determination and spatial distribution of
      constituents.
AB  - Independent component analysis (ICA) was used as a blind source separation method
      on a Raman image of a pharmaceutical tablet. Calculations were performed without
      a priori knowledge concerning the formulation. The aim was to extract the pure
      signals from the initial data set in order to examine the distribution of actives
      and major excipients within the tablet. As a method based on the decomposition of
      a matrix of mixtures of several components, the number of independent component
      to choose is a critical step of the analysis. The ICA_by_blocks method, based on
      the calculation of several models using an increasing number of independent
      components on initial matrix blocks, was used. The calculated ICA signals were
      compared with the pure spectra of the formulation compounds. High correlations
      between the two active principal ingredient spectra and their corresponding
      calculated signals were observed giving a good overview of the distributions of
      these compounds within the tablet. Information from the major excipients (lactose
      and avicel) was found in several independent components but the ICA approach
      provides high level of information concerning their distribution within the
      tablet. However, the results could vary considerably by changing the number of
      independent components or the preprocessing method. Indeed, it was shown that
      under-decomposition of the matrix could lead to better signal quality (compared
      to the pure spectra) but in that case the contributions due to minor components
      or effects were not correctly identified and extracted. On the contrary, over
      decomposition of the original dataset could provide information about low
      concentration compounds at the expense of some loss of signal interpretability
      for the other compounds. 

PMID- 24333707
TI  - Application of quantitative 1H NMR for the calibration of protoberberine alkaloid
      reference standards.
AB  - Quantitative nuclear magnetic resonance spectroscopy (qNMR) has been developed
      into an important tool in the drug analysis, biomacromolecule detection, and
      metabolism study. Compared with mass balance method, qNMR method bears some
      advantages in the calibration of reference standard (RS): it determines the
      absolute amount of a sample; other chemical compound and its certified reference
      material (CRM) can be used as internal standard (IS) to obtain the purity of the
      sample. Protoberberine alkaloids have many biological activities and have been
      used as reference standards for the control of many herbal drugs. In present
      study, the qNMR methods were developed for the calibration of berberine
      hydrochloride, palmatine hydrochloride, tetrahydropalmatine, and phellodendrine
      hydrochloride with potassium hydrogen phthalate as IS. Method validation was
      carried out according to the guidelines for the method validation of Chinese
      Pharmacopoeia. The results of qNMR were compared with those of mass balance
      method and the differences between the results of two methods were acceptable
      based on the analysis of estimated measurement uncertainties. Therefore, qNMR is
      an effective and reliable analysis method for the calibration of RS and can be
      used as a good complementarity to the mass balance method. 

PMID- 24333708
TI  - K(V)7 potassium channels: a new therapeutic target in smooth muscle disorders.
AB  - Potassium channels are key regulators of smooth muscle tone, with increases in
      activity resulting in hyperpolarisation of the cell membrane, which acts to
      oppose vasoconstriction. Several potassium channels exist within smooth muscle,
      but the KV7 family of voltage-gated potassium channels have been identified as
      being crucial mediators of this process in a variety of smooth muscle. Recently,
      KV7 channels have been shown to be involved in the pathogenesis of hypertension,
      as well as being implicated in other smooth muscle disorders, providing a new and
      inviting target for smooth muscle disorders. 

PMID- 24333709
TI  - Potential use of a self-dying reporter bacterium to determine the bioavailability
      of aged phenanthrene in soil: comparison with physicochemical measures.
AB  - The potential bioavailability of phenanthrene aged in soil was determined by
      using a self-dying reporter bacterium, and the results were compared to two
      physicochemical measures, Tenax TA((r)) bead-assisted desorption, and
      hydroxypropyl-beta-cyclodextrin (HPCD) extraction. The reporter bacterium,
      capable of degrading phenanthrene as a sole carbon and energy source, was
      genetically reconstructed to die when it degrades phenanthrene. Therefore,
      population change of the reporter cells can be viewed as the quantification of
      bioavailable phenanthrene. When Ottawa sand was used as an aging matrix, the
      amounts of bioavailable phenanthrene (i.e. little gradual decrease) were similar,
      regardless of aging time, and consistent between the reporter bacterium and the
      two physicochemical measures. However, decrease in bioavailable phenanthrene with
      aging was readily evident in sandy loam with organic matter of 11.5%, with all
      three measures. More importantly, when the reporter bacterium was used, a rapid
      and significant decrease in the bioavailable fraction from 1.00 to 0.0431 was
      observed. The extent of decrease in bioavailable fraction was less than 40% in
      the two physicochemical measures, but was nearly 100% in the reporter bacterium,
      during the first 3 months of aging. Our results suggest that the phenanthrene
      fraction available to bacterial degradation, and probably the fraction that
      really manifests toxicity, may be much smaller than the fractions predicted with
      the physicochemical measures. 

PMID- 24333710
TI  - Adsorptive removal of phenolic compounds using cellulose acetate phthalate
      alumina nanoparticle mixed matrix membrane.
AB  - Mixed matrix membranes (MMMs) were prepared using alumina nanoparticles and
      cellulose acetate phthalate (CAP) by varying concentration of nanoparticles in
      the range of 10 to 25wt%. The membranes were characterized by scanning electron
      micrograph, porosity, permeability, molecular weight cut off, contact angle,
      surface zeta potential, mechanical strength. Addition of nanoparticles increased
      the porosity, permeability of the membrane up to 20wt% of alumina. pH at point of
      zero charge of the membrane was 5.4. Zeta potential of the membrane became more
      negative up to 20wt% of nanoparticles. Adsorption of phenolic derivatives,
      catechol, paranitrophenol, phenol, orthochloro phenol, metanitrophenol, by MMMs
      were investigated. Variation of rejection and permeate flux profiles were studied
      for different solutes as a function of various operating conditions, namely,
      solution pH, solute concentration in feed and transmembrane pressure drop.
      Difference in rejection of phenolic derivatives is consequence of interplay of
      surface charge and adsorption by alumina. Adsorption isotherm was fitted for
      different solutes and effects of pH were investigated. Catechol showed the
      maximum rejection 91% at solution pH 9. Addition of electrolyte reduced the
      rejection of solutes. Transmembrane pressure drop has insignificant effects on
      solute rejection. Competitive adsorption reduced the rejection of individual
      solute. 

PMID- 24333711
TI  - Guar gum coupled microscale ZVI for in situ treatment of CAHs: continuous-flow
      column study.
AB  - A column study was performed under in situ conditions to evaluate to which extend
      the inactivation of the microscale zerovalent iron (mZVI) by guar gum occurs
      under continuous flow conditions. Five aquifer containing columns were set up
      under different conditions. Efficient removal of trichloroethene was observed for
      the column amended by mZVI. Stabilization of the mZVI with guar gum led to
      slightly reduced activity. More reduced reactivity was observed in the poisoned
      column containing guar gum stabilized mZVI. This confirms that soil
      microorganisms can degrade guar gum and that subsequent removal of the
      oligosaccharides by the groundwater flow (flushing effect) can reactivate the
      mZVI. After more than six months of continuous operation the columns were
      dismantled. DNA-based qPCR analysis revealed that mZVI does not significantly
      affect the bacterial community, while guar gum stabilized mZVI particles can even
      induce bacterial growth. Overall, this study suggests that the temporarily
      decreased mZVI reactivity due to guar gum, has a rather limited impact on the
      performance of in situ reactive zones. The presence of guar gum slightly reduced
      the reactivity of iron, but also slowed down the iron corrosion rate which
      prolongs the life time of reactive zone. 

PMID- 24333712
TI  - Locating sources of hazardous gas emissions using dual pollution rose plots and
      open path Fourier transform infrared spectroscopy.
AB  - A new approach employing two pollution rose plots to locate the sources of
      multiple hazardous gas emissions was proposed and tested in an industrial area.
      The data used for constructing the pollution rose plots were obtained from two
      side-by-side measurements of open-path Fourier Transform Infrared (OP-FTIR)
      spectrometers during one week of continuous analysis on the rooftop of a
      semiconductor plant. Hazardous gases such as CF4, C2F6, CH3OH, NH3, NO2, and SF6
      were found and quantified at the ppb level by both OP-FTIR measurement sites. The
      data of the top 20% highest concentrations and associated wind directions were
      used to construct the pollution rose plots. Pollution source probability contours
      for each compound were constructed using the probability-product of directional
      probability from two pollution rose plots. Hot spots for SF6, CF4, NO2, and C2F6
      pointed to the stack area of the plant, but the sources of CH3OH and NH3 were
      found outside of this plant. The influences of parameters for this approach such
      as the variation in wind direction, lower limit concentration threshold and the
      nearby buildings were discussed. 

PMID- 24333713
TI  - Ciprofloxacin oxidation by UV-C activated peroxymonosulfate in wastewater.
AB  - This work aimed at demonstrating the advantages to use sulfate radical anion for
      eliminating ciprofloxacin residues from treated domestic wastewater by comparing
      three UV-254nm based advanced oxidation processes: UV/persulfate (PDS),
      UV/peroxymonosulfate (PMS) and UV/H2O2. In distilled water, the order of
      efficiency was UV/PDS>UV/PMS>UV/H2O2 while in wastewater, the most efficient
      process was UV/PMS followed by UV/PDS and UV/H2O2 mainly because PMS
      decomposition into sulfate radical anion was activated by bicarbonate ions. CIP
      was fully degraded in wastewater at pH 7 in 60min for a [PMS]/[CIP] molar ratio
      of 20. Nine transformation products were identified by liquid chromatography-high
      resolution-mass spectrometry allowing for the establishment of degradation
      pathways in the UV/PMS system. Sulfate radical anion attacks prompted
      transformations at the piperazinyl ring through a one electron oxidation
      mechanism as a major pathway while hydroxyl radical attacks were mainly
      responsible for quinolone moiety transformations as a minor pathway. Sulfate
      radical anion generation has made UV/PMS a kinetically effective process in
      removing ciprofloxacin from wastewater with the elimination of ciprofloxacin
      antibacterial activity. 

PMID- 24333714
TI  - Contribution of hot spring bacterial consortium in cadmium and lead
      bioremediation through quadratic programming model.
AB  - In the present investigation, a number of experiments have been conducted to
      isolate microbial strains from Taptapani Hot Spring Odisha, India for
      bioremediation of cadmium and lead. The strains Stenotrophomonas maltophilia
      (SS1), Aeromonas veronii (SS2) and Bacillus barbaricus (SS3) have shown better
      adaptation to metal tolerance test, with different concentrations of cadmium and
      lead and hence have been selected for further studies of metal microbial
      interaction and optimization. The results of bioremediation process indicate that
      consortium of thermophilic isolates adsorbed heavy metals more effectively than
      the individually treated isolates. Therefore, A 24 full factorial central
      composite design has been employed to analyze the effect of metal ion
      concentration, microbial concentration and time on removal of heavy metals with
      consortium. Analysis of variance (ANOVA) shows a high coefficient of
      determination value. The kinetic data have been fitted to pseudo-first order and
      second-order models. The isotherm equilibrium data have been well fitted by the
      Langmuir and Freundlich models. The optimum removal conditions determined for
      initial ion concentration was 0.3g/l; contact time 72h; microbial concentration,
      3ml/l; and pH 7. At optimum adsorption conditions, the adsorption of cadmium and
      lead are found to be 92% and 93%, respectively, and presence of metals was
      confirmed through EDS analysis. 

PMID- 24333715
TI  - Microcosm study on fate of polybrominated diphenyl ethers (PBDEs) in contaminated
      mangrove sediment.
AB  - Polybrominated diphenyl ethers (PBDEs) are toxic and ubiquitous environmental
      contaminants, but their fate in aquatic environments is not clear. A mangrove
      microcosm study was employed to investigate the fate of two abundant congeners,
      BDE-47 and BDE-209, in contaminated sediment. After seven months, more than 90%
      of the spiked BDE-47 in the mangrove sediment was removed with the formation of
      lower brominated PBDEs, including BDE-28, -17, -15, -8, -7/4, suggesting that
      microbial debromination was the main contributor. Debromination of BDE-209 was
      also observed in the sediment but its dissipation rate was significantly lower
      than BDE-47. All these congeners were taken up, translocated and accumulated into
      the tissues of two typical mangrove plants, Kandelia obovata and Avicennia
      marina. PBDEs, even at very high contamination levels, in the sediment (5000ngg(
      1)) and the debrominated congeners did not pose any adverse effect on the dry
      weight, augmentation and root/shoot ratio of either mangrove species. This is the
      first study to reveal that anaerobic microbial debromination and uptake by
      mangrove plants are the key processes controlling the fate of PBDEs in mangrove
      sediment. 

PMID- 24333716
TI  - Enhanced ozonation degradation of di-n-butyl phthalate by zero-valent zinc in
      aqueous solution: performance and mechanism.
AB  - Enhanced ozonation degradation of di-n-butyl phthalate (DBP) by zero-valent zinc
      (ZVZ) has been investigated using a semi-continuous reactor in aqueous solution.
      The results indicated that the combination of ozone (O3) and ZVZ showed an
      obvious synergetic effect, i.e. an improvement of 54.8% on DBP degradation was
      obtained by the O3/ZVZ process after 10min reaction compared to the cumulative
      effect of O3 alone and O2/ZVZ. The degradation efficiency of DBP increased
      gradually with the increase of ZVZ dosage, enhanced as solution pH increasing
      from 2.0 to 10.0, and more amount of DBP was degraded with the initial
      concentration of DBP arising from 0.5 to 2.0mgL(-1). Recycling use of ZVZ
      resulted in the enhancement of DBP degradation, because the newly formed zinc
      oxide took part in the reaction. The mechanism investigation demonstrated that
      the enhancement effect was attributed to the introduction of ZVZ, which could
      promote the utilization of O3, enhance the formation of superoxide radical by
      reducing O2 via one-electron transfer, accelerate the production of hydrogen
      peroxide and the generation of hydroxyl radical. Additionally, the newly formed
      zinc oxide on ZVZ surface also contributed to the enhancement of DBP degradation
      in the recycling use of ZVZ. Most importantly, the O3/ZVZ process was also
      effective in enhanced ozonation degradation of DBP under the background of actual
      waters. 

PMID- 24333717
TI  - Metabolomics in diagnosis and biomarker discovery of colorectal cancer.
AB  - Colorectal cancer (CRC), a major public health concern, is the second leading
      cause of cancer death in developed countries. There is a need for better
      preventive strategies to improve the patient outcome that is substantially
      influenced by cancer stage at the time of diagnosis. Patients with early stage
      colorectal have a significant higher 5-year survival rates compared to patients
      diagnosed at late stage. Although traditional colonoscopy remains the effective
      means to diagnose CRC, this approach generally suffers from poor patient
      compliance. Thus, it is important to develop more effective methods for early
      diagnosis of this disease process, also there is an urgent need for biomarkers to
      diagnose CRC, assess disease severity, and prognosticate course. Increasing
      availability of high-throughput methodologies open up new possibilities for
      screening new potential candidates for identifying biomarkers. Fortunately,
      metabolomics, the study of all metabolites produced in the body, considered most
      closely related to a patient's phenotype, can provide clinically useful
      biomarkers applied in CRC, and may now open new avenues for diagnostics. It has a
      largely untapped potential in the field of oncology, through the analysis of the
      cancer metabolome to identify marker metabolites defined here as surrogate
      indicators of physiological or pathophysiological states. In this review we take
      a closer look at the metabolomics used within the field of colorectal cancer.
      Further, we highlight the most interesting metabolomics publications and discuss
      these in detail; additional studies are mentioned as a reference for the
      interested reader. 

PMID- 24333718
TI  - Mesenchymal stromal cell ciliogenesis is abrogated in response to tumor necrosis
      factor-alpha and requires NF-kappaB signaling.
AB  - The primary cilium is a cell surface-anchored sensory organelle which expression
      is lost in hypoxic cancer cells and during mesenchymal stromal cells (MSC)
      adaptation to low oxygen levels. Since pro-inflammatory cues are among the early
      events which promote tumor angiogenesis, we tested the inflammatory cytokine
      tumor necrosis factor (TNF)-alpha and found that it triggered a dose-dependent
      loss of the primary cilia in MSC. This loss was independent of IFT88 expression,
      was abrogated by progranulin, an antagonist of the TNF receptor and required the
      NF-kappaB signaling intermediates IkappaB kinase alpha, beta, and gamma, as well
      as NF-kappaB p65. These findings strengthen the concept that the primary cilium
      may serve as a biomarker reflecting the tumor-supporting potential of MSC and
      their capacity to adapt to hypoxic and pro-inflammatory cues. 

PMID- 24333719
TI  - Lipopolysaccharide induces the interactions of breast cancer and endothelial
      cells via activated monocytes.
AB  - The adhesion of circulating cancer cells to vascular endothelium is a key step in
      hematogenous metastasis. Cancer cell-endothelium interactions are mediated by
      cell adhesion molecules that can also be involved in the arrest of monocytes and
      other circulating leukocytes on endothelium in inflammation. Static and
      microfluidic flow adhesion assays as well as flow cytometry were conducted in
      this study to elucidate the role of monocytes, bacterial lipopolysaccharide
      (LPS), and histamine in breast cancer cell adhesion to vascular endothelial
      cells. Tumor necrosis factor-alpha (TNF-alpha) released from LPS-treated
      monocytes triggered the expression of intercellular cell adhesion molecule-1
      (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells.
      Histamine augmented the TNF-alpha effect, leading to a high number of arrested
      breast cancer cells under both static and shear flow conditions. LPS-treated
      monocytes were shown to enhance the arrest of breast cancer cells by anchoring
      the cancer cells to activated endothelial cells. This anchorage was achieved by
      binding cancer cell ICAM-1 to monocyte beta2 integrins and binding endothelial
      ICAM-1 and VCAM-1 to monocyte beta1 and beta2 integrins. The results of this
      study imply that LPS is an important risk factor for cancer metastasis and that
      the elevated serum level of histamine further increases the risk of LPS-induced
      cancer metastasis. Preventing bacterial infections is essential in cancer
      treatment, and it is particularly vital for cancer patients affected by allergy. 

PMID- 24333720
TI  - NVP-BEZ235, a dual PI3K/mTOR inhibitor, inhibits osteosarcoma cell proliferation
      and tumor development in vivo with an improved survival rate.
AB  - Despite recent improvements in chemotherapy and surgery, the problem of non
      response osteosarcoma to chemotherapy remains, and is a parameter that is
      critical for prognosis. The present work investigated the therapeutic value of
      NVP-BEZ235, a dual class I PI3K/mTOR inhibitor. NVP-BEZ235 inhibited osteosarcoma
      cell proliferation by inducing G0/G1 cell cycle arrest with no caspase
      activation. In murine pre-clinical models, NVP-BEZ235 significantly slowed down
      tumor progression and ectopic tumor bone formation with decreased numbers of
      Ki67(+) cells and reduced tumor vasculature. Finally, NVP-BEZ235 considerably
      improved the survival rate of mice with osteosarcoma. Taken together, the results
      of the present work show that NVP-BEZ235 exhibits therapeutic interest in
      osteosarcoma and may be a promising adjuvant drug for bone sarcomas.

PMID- 24333721
TI  - Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression.
AB  - Increasing evidence has indicated that prolonged use of anti-VEGF (vascular
      endothelial growth factor) agents for cancer therapy promotes tumor resistance.
      To gain insight into the molecular mechanism underlying resistance to anti-VEGF
      therapy, we developed a mouse Lewis lung carcinoma (LLC) cell line that is
      resistant to treatment with a potent VEGF inhibitor, VEGF-Trap, through repeated
      in vivo selection. We compared the transcriptome profiles of resistant and non
      resistant tumor cells using RNA-seq analysis. VEGF-C was significantly up
      regulated in resistant tumor cells, as determined by quantitative real-time PCR
      and immunohistochemical analyses. Inhibition of VEGF-C in resistant cells
      suppressed endothelial cell migration in vitro and partially restored sensitivity
      to VEGF-Trap treatment in vivo. Our findings indicate that tumors may develop
      resistance to anti-VEGF therapy by activating the VEGF-C pathway. 

PMID- 24333722
TI  - Protein kinase CK2 is required for the recruitment of 53BP1 to sites of DNA
      double-strand break induced by radiomimetic drugs.
AB  - The ataxia telangiectasia mutated (ATM) signaling pathway responds rapidly to DNA
      double-strand breaks (DSBs) and it is characterized by recruitment of sensor,
      mediator, transducer and repair proteins to sites of DNA damage. Data suggest
      that CK2 is implicated in the early cellular response to DSBs. We demonstrate
      that CK2 binds constitutively the adaptor protein 53BP1 through the tandem Tudor
      domains and that the interaction is disrupted upon induction of DNA damage. Down
      regulation of CK2 results in significant reduction of (i) 53BP1 foci formation,
      (ii) binding to dimethylated histone H4 and (iii) ATM autophosphorylation. Our
      data suggest that CK2 is required for 53BP1 accumulation at sites of DSBs which
      is a prerequisite for efficient activation of the ATM-mediated signaling pathway.

PMID- 24333723
TI  - Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis.
AB  - Hypoxia and lymphangiogenesis are closely related processes that play a pivotal
      role in tumor invasion and metastasis. Intratumoral hypoxia is exacerbated as a
      result of oxygen consumption by rapidly proliferating tumor cells, insufficient
      blood supply and poor lymph drainage. Hypoxia induces functional responses in
      lymphatic endothelial cells (LECs), including cell proliferation and migration.
      Multiple factors (e.g., ET-1, AP-1, C/EBP-delta, EGR-1, NF-kappaB, and MIF) are
      involved in the events of hypoxia-induced lymphangiogenesis. Among them, HIF
      1alpha is known to be the master regulator of cellular oxygen homeostasis,
      mediating transcriptional activation of lymphangiogenesis via regulation of
      signaling cascades like VEGF-A/-C/-D, TGF-beta and Prox-1 in experimental and
      human tumors. Although the underlying molecular mechanisms remain incompletely
      elucidated, the investigation of lymphangiogenesis in hypoxic conditions may
      provide insight into potential therapeutic targets for lymphatic metastasis. 

PMID- 24333724
TI  - CD68(+)HLA-DR(+) M1-like macrophages promote motility of HCC cells via NF
      kappaB/FAK pathway.
AB  - TAM is a prominent component of inflammatory microenvironment, presenting M1 and
      M2 polarized states in HCC. The objective of this study is to investigate the
      relationship between M1-polarized macrophages and metastasis in HCC. We used
      immunohistochemical double-staining method to inspect the infiltration of
      CD68(+)HLA-DR(+) M1-like macrophages in HCC tissues. The M1-polarized macrophage
      was derived from THP-1 cell treated by LPS and IFN-gamma in vitro. Transwell
      migration assay was used to evaluate whether the M1-polarized macrophage enhanced
      motility of HCC cells in the presence or absence of NF-kappaB inhibitor Bay 11
      7802. The activation of NF-kappaB and FAK signaling pathways was examined by
      Western blot assay. Our results showed that the density of CD68(+)HLA-DR(+) TAM
      in the HCC with metastasis is significantly higher than that in the HCC without
      metastasis. Moreover, the conditioned medium from the M1 macrophages promote the
      migration of HCC cells and induced the activation of NF-kappaB and FAK signaling.
      The promoted migration of HCC cells was abrogated by the Bay 11-7802, as well as
      the activation of NF-kappaB and FAK pathway. Our findings implied a pro
      metastatic role of M1-like TAM in HCC. 

PMID- 24333725
TI  - Development and characterization of a colon PDX model that reproduces drug
      responsiveness and the mutation profiles of its original tumor.
AB  - Cultures of primary tumors are very useful as a personalized screening system for
      effective therapeutic options. We here describe an effective method of
      reproducing human primary colon tumors through primary culture and a mouse
      xenograft model. A total of 199 primary colon tumor cultures were successfully
      established under optimized conditions to enrich for tumor cells and to expand it
      for long-term storage in liquid nitrogen. To examine whether these stored
      cultures retained original tumor properties, fifty primary cultures were
      xenografted into NOD-SCID mouse. Histological and tumor marker analysis of four
      representative tumor xenografts revealed that all of the xenograft retained its
      primary tumor characteristics. Oncomap analysis further showed no change in the
      major mutations in the xenografts, confirming that our method faithfully
      reproduced human colon tumors. A drug sensitivity assay revealed that two of the
      primary cultures were hypersensitive to oxaliplatin rather than 5-FU, which was
      used in the patients, suggesting it as an effective therapeutic option. We thus
      present an effective, reproducible preclinical model for testing various
      personalized therapeutic options in colon cancer patients. 

PMID- 24333726
TI  - Cancer stem cells: A contentious hypothesis now moving forward.
AB  - Cancer stem cells are a progressive concept to account for the cell biological
      nature of cancer. Despite the controversies regarding the cancer stem cell model,
      it has the potential to provide a foundation for new innovative treatment
      targeting the roots of cancer. The last two years have witnessed exceptional
      progress in cancer stem cell research, in particular on solid tumours, which
      holds promise for improved treatment outcomes. Here, we review recent advances in
      cancer stem cell research, discuss challenges in the field and explore future
      strategies and opportunities in cancer stem cell studies to overcome resistance
      to chemotherapy.

PMID- 24333727
TI  - MicroRNA miR-302 inhibits the tumorigenicity of endometrial cancer cells by
      suppression of Cyclin D1 and CDK1.
AB  - MicroRNA miR-302 has been found to induce some tumor cell lines to
      "transdifferentiate" into miRNA-induced pluripotent stem cells (mirPS), thereby
      inhibiting tumor cell proliferation and reducing tumorigenicity. This study
      firstly found that miR-302 inhibited the proliferation and migration of
      endometrial cell line, Ishikawa and HEC-1-B, and arrested cell cycle at the G2/M
      phase. In addition, miR-302 inhibited tumorigenicity in immunodeficient mice
      transplanted with Ishikawa cells. Microarray and Western blotting results showed
      that miR-302 significantly inhibited CDK1 and Cyclin D1 gene expression in
      Ishikawa cells. MiR-302 directly targeted Cyclin D1, but indirectly regulated
      CDK1 gene expression. 

PMID- 24333728
TI  - Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and
      down-regulates the expression and function.
AB  - P-glycoprotein (P-gp)/ABCB1 is a key molecule of multidrug resistance in cancer.
      Protein phosphatase (PP) 2A, regulatory subunit B, gamma (PPP2R3C), which is a
      regulatory subunit of PP2A and PP5, was identified as a binding candidate to P
      gp. Immunoprecipitation-western blotting revealed that PP5 and PPP2R3C were
      coprecipitated with P-gp, while PP2A was not. PP5/PPP2R3C dephosphorylated
      protein kinase A/protein kinase C-phosphorylation of P-gp. Knockdown of PP5
      and/or PPP2R3C increased P-gp expression and lowered the sensitivity to
      vincristine and doxorubicin. Consequently, our results indicate that PP5/PPP2R3C
      negatively regulates P-gp expression and function. 

PMID- 24333729
TI  - The ING tumor suppressor genes: status in human tumors.
AB  - ING genes (ING1-5) were identified has tumor suppressor genes. ING proteins are
      characterized as Type II TSGs since they are involved in the control of cell
      proliferation, apoptosis and senescence. They may also function as Type I TSGs
      since they are also involved in DNA replication and repair. Most studies have
      reported that they are frequently lost in human tumors and epigenetic mechanisms
      or misregulation of their transcription may be involved. Recently, studies have
      described that this loss may be caused by microRNA inhibition. Here, we summarize
      the current knowledge on ING functions, their involvement in tumor suppression
      and, in order to give a full assessment of the current knowledge, we review all
      the studies that have examined ING status in human cancers. 

PMID- 24333730
TI  - The role of basic fibroblast growth factor in glioblastoma multiforme and
      glioblastoma stem cells and in their in vitro culture.
AB  - Glioblastoma multiforme (GBM) is the most malignant form of central nervous
      system tumor, and current therapies are largely ineffective at treating the
      cancer. Developing a more complete understanding of the mechanisms controlling
      the tumor is important in order to explore new possible treatment options. It is
      speculated that the presence of glioblastoma stem or stem-like cells (GSCs), a
      rare type of pluripotent cancer cell that possesses the ability to self-renew and
      generate tumors, could be an important factor contributing to the resistance to
      treatment and deadliness of the cancer. A comprehensive knowledge of the
      mechanisms controlling the expression and properties of GSCs is currently
      lacking, and one promising area for further exploration is in the influence of
      basic fibroblast growth factor (FGF-2) on GSCs. Recent studies reveal that FGF-2
      plays a significant part in regulating GBM, and the growth factor is commonly
      included as a supplement in media used to culture GSCs in vitro. However, the
      particular role that FGF-2 plays in GSCs has not been as extensively explored.
      Therefore, understanding how FGF-2 is involved in GSCs and in GBMs could be an
      important step towards a more complete comprehension of the managing the disease.
      In this review, we look at the structure, signaling pathways, and specific role
      of FGF-2 in GBM and GSCs. In addition, we explore the use of FGF-2 in cell
      culture and using its synthetic analogs as a potential alternative to the growth
      factor in culture medium. 

PMID- 24333731
TI  - LRH1 as a driving factor in pancreatic cancer growth.
AB  - Liver receptor homolog 1 (LRH1), directs the development and differentiation of
      embryonic pancreas, and is overexpressed in pancreatic cancer (PC). We
      hypothesized that LRH1 promotes PC growth. Cell proliferation and tumorigenicity
      in nude mice were compared between empty vector-transfected (control) and stable
      LRH1-overexpressed PC cell lines. The subsequent tumor burden, vasculature
      development, and histologic features were evaluated. LRH1 overexpression enhanced
      the expression of downstream target genes (cyclin D1/E1) and stimulated cell
      proliferation in PC cell lines. LRH1 upregulated cyclin E1 truncated T1/T2
      isoforms expression which may occur through ERalpha-calpain1 signaling. Compared
      with the control, LRH1 overexpressing stable cells generated tumors with
      increased weight, proliferation index and enhanced angiogenesis. Cyclin D1/E1 and
      calpain1 were overexpressed in human PC tumors compared to adjacent normal
      pancreas. These observations demonstrate that LRH1 promotes PC growth and
      angiogenesis, suggesting that LRH1 is a driving factor in tumorigenesis and may
      serve as a potential therapeutic target. 

PMID- 24333732
TI  - Imatinib sensitizes endometrial cancer cells to cisplatin by targeting CD117
      positive growth-competent cells.
AB  - The use of molecular target therapy has not been established for endometrial
      cancer. The present study investigated the potential therapeutic strategy of
      targeting CD117-positive cancer cells as a novel molecular target therapy. FACS
      sorted CD117(+) cells isolated from endometrial cancer cell lines (Ishikawa or
      MFE280 cells) exhibited higher proliferative capacity in vitro and colony forming
      activity on soft agar, and decreased sensitivity to cisplatin, compared to CD117(
      ) cells. Immunohistochemical analyses with surgical specimens of endometrial
      cancers showed that high CD117 expression was tightly linked to advanced FIGO
      stages, myometrial invasion and histological grade, and was significantly
      associated with poor overall survival and relapse-free survival (Kaplan-Meier
      analysis; p<0.001, log-rank test). The Cox-regression hazard model identified
      high CD117 expression to be an independent prognostic factor for survival
      (p<0.05). In vitro assay confirmed that stem cell factor (SCF), a ligand of
      CD117, was produced specifically in CD117(+) cells of endometrial cancer, and the
      colony-forming activity were abrogated by adding anti-SCF antibody, indicating an
      SCF-dependent growth property. Imatinib was confirmed to selectively target
      CD117(+) cells in vitro, and synergistically enhanced the anti-tumor effect of
      low dose cisplatin in vivo, which showed only modest effects when used as a
      single use. These findings suggest that CD117 can be a marker of aggressive
      behavior of cells as well as an independent prognostic marker in endometrial
      cancer. Targeting of the SCF/CD117 axis by imatinib sensitized endometrial cancer
      cells to cisplatin, proposing a novel therapeutic strategy for this tumor type. 

PMID- 24333733
TI  - The role of kinin receptors in cancer and therapeutic opportunities.
AB  - Kinins are generated within inflammatory tissue microenvironments, where they
      exert diverse functions, including cell proliferation, leukocyte activation, cell
      migration, endothelial cell activation and nociception. These pleiotropic
      functions depend on signaling through two cross talking receptors, the
      constitutively expressed kinin receptor 2 (B2R) and the inducible kinin receptor
      1 (B1R). We have reviewed evidence, which supports the concept that kinin
      receptors, especially kinin receptor 1, are promising targets for cancer therapy,
      since (1) many tumor cells express aberrantly high levels of these receptors; (2)
      some cancers produce kinins and use them as autocrine factors to stimulate their
      growth; (3) activation of kinin receptors leads to activation of macrophages,
      dendritic cells and other cells from the tumor microenvironment; (4) kinins have
      pro-angiogenic properties; (5) kinin receptors have been implicated in cancer
      migration, invasion and metastasis; and (6) selective antagonists for either B1R
      or B2R have shown anti-proliferative, anti-inflammatory, anti-angiogenic and anti
      migratory properties. The multiple cross talks between kinin receptors and renin
      angiotensin system (RAS) as well as its implications for targeting KKS or RAS for
      the treatment of malignancies are also discussed. It is expected that B1R
      antagonists would interfere less with housekeeping functions and therefore would
      be attractive compounds to treat selected types of cancer. Reliable clinical
      studies are needed to establish the translatability of these data to human
      settings and the usefulness of kinin receptor antagonists. 

PMID- 24333734
TI  - Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor
      gene in paediatric intracranial ependymoma.
AB  - Promoter hypermethylation and transcriptional silencing is a common epigenetic
      mechanism of gene inactivation in cancer. To identify targets of epigenetic
      silencing in paediatric intracranial ependymoma, we used a pharmacological
      unmasking approach through treatment of 3 ependymoma short-term cell cultures
      with the demethylating agent 5-Aza-2'-deoxycytidine followed by global expression
      microarray analysis. We identified 55 candidate epigenetically silenced genes,
      which are involved in the regulation of apoptosis, Wnt signalling, p53 and cell
      differentiation. The methylation status of 26 of these genes was further
      determined by combined bisulfite restriction analysis (COBRA) and genomic
      sequencing in a cohort of 40 ependymoma samples. The most frequently methylated
      genes were BEX1 (27/40 cases), BAI2 (20/40), CCND2 (18/40), and CDKN2A (14/40). A
      high correlation between promoter hypermethylation and decreased gene expression
      levels was established by real-time quantitative PCR, suggesting the involvement
      of these genes in ependymoma tumourigenesis. Furthermore, ectopic expression of
      brain-expressed X-linked 1 (BEX1) in paediatric ependymoma short-term cell
      cultures significantly suppressed cell proliferation and colony formation. These
      data suggest that promoter hypermethylation contributes to silencing of target
      genes in paediatric intracranial ependymoma. Epigenetic inactivation of BEX1
      supports its role as a candidate tumour suppressor gene in intracranial
      ependymoma, and a potential target for novel therapies for ependymoma in
      children. 

PMID- 24333735
TI  - Enhancement of radiotherapy efficacy by docetaxel-loaded gelatinase-stimuli PEG
      Pep-PCL nanoparticles in gastric cancer.
AB  - Docetaxel (DOC) is widely used as radiosensitizer in various tumors, including
      gastric cancer (GC), but its therapeutic effect remains to be improved. In this
      study, using docetaxel-loaded nanoparticles (DOC-NPs) based on gelatinase-stimuli
      strategy, we compared their radioenhancement efficacy with docetaxel in GC.
      Compared with DOC, radiosensitization of DOC-NPs was improved significantly
      (sensitization enhancement ratio increased 1.09-fold to 1.24-fold, P<0.01) in all
      three gelatinase overexpressing GC cells, while increased slightly (1.02-fold,
      P=0.38) in gelatinase deficient normal gastric mucosa cells. The improved
      radiosensitization efficacy was associated with enhanced G2/M arrest, increased
      reactive oxygen species (ROS), more effective DSBs and promoted apoptosis. More
      importantly, the radiosensitization efficacy of DOC-NPs (estimated as ''very
      active'') was more prominent than DOC (estimated as ''moderately active'') by
      intravenous injection in xenograft. In conclusion, DOC-NPs are highly selective
      radiosensitizers in gelatinase over-expressing tumors, and more effective than
      DOC. By manipulating the common microenvironment difference between tumor and
      normal tissue, gelatinase-mediated nanoscale delivery system serves as a
      potential strategy possessing both universality and selectivity for
      radiosensitizers.

PMID- 24333736
TI  - Capillarisin inhibits constitutive and inducible STAT3 activation through
      induction of SHP-1 and SHP-2 tyrosine phosphatases.
AB  - Signal transducers and activators of transcription (STAT)-3 is a latent cytosolic
      transcription factor that has been closely associated with survival,
      proliferation, chemoresistance, and metastasis of tumor cells. Whether the anti
      proliferative, pro-apoptotic, and anti-metastatic effects of capillarisin (CPS),
      derived from Artemisia capillaris (Compositae), are linked to its capability to
      inhibit STAT3 activation was investigated. We found that CPS specifically
      inhibited both constitutive and inducible STAT3 activation at tyrosine residue
      705 but not at serine residue 727 in human multiple myeloma cells. Besides the
      inhibition of STAT3 phosphorylation, CPS also abrogated STAT3 constitutive
      activity and nuclear translocation. The suppression of STAT3 was mediated through
      the inhibition of activation of upstream JAK1, JAK2, and c-Src kinases. Treatment
      with the protein tyrosine phosphatase (PTP) inhibitor pervanadate treatment
      reversed the CPS-induced down-regulation of JAK1/2 and STAT3, thereby suggesting
      the involvement of a PTP. Indeed, knockdown of the SHP-1 and SHP-2 genes by small
      interfering RNA suppressed the ability of CPS to inhibit JAK1 and STAT3
      activation, suggesting the critical role of both SHP-1 and SHP-2 in its possible
      mechanism of action. CPS downregulated the expression of STAT3-regulated
      antiapoptotic and proliferative gene products; and this correlated with
      suppression of cell viability, the accumulation of cells in sub-G1 phase of cell
      cycle and induction of apoptosis. Moreover, CPS potentiated bortezomib-induced
      apoptotic effects in MM cells, and this correlated with down-regulation of
      various gene products that mediate cell proliferation (Cyclin D1 and COX-2), cell
      survival (Bcl-2, Bcl-xl, IAP1, IAP2, and Survivin), invasion (MMP-9), and
      angiogenesis (VEGF). Thus, overall, our results suggest that CPS is a novel
      blocker of STAT3 activation and thus may have a potential in negative regulation
      of growth, metastasis, and chemoresistance of tumor cells. 

PMID- 24333737
TI  - Residential radon and lung cancer in never smokers. A systematic review.
AB  - Radon exposure is considered the second cause of lung cancer and the first in
      never smokers. We aim to assess the effect of residential radon exposure on the
      risk of lung cancer in never smokers through a systematic review applying
      predefined inclusion and exclusion criteria. 14 Studies were included. Some of
      them point to a relationship between residential radon and lung cancer while
      others show no association. Further studies are necessary to test this
      association and to assess if other risk factors such as environmental tobacco
      smoke could modify the effect of residential radon exposure on lung cancer. 

PMID- 24333739
TI  - Circadian properties of cancer stem cells in glioma cell cultures and
      tumorspheres.
AB  - Increased cancer risk is linked to disruption of circadian rhythms. Cancer stem
      cells (CSCs) are a known cause of cancer aggressiveness, but their circadian
      properties have not been described. We discovered circadian rhythms in gene
      expression within C6 glioma tumorspheres enriched in CSCs and found that the
      circadian clock is particularly robust in medium lacking any growth factors. A
      method is introduced for identifying individual CSCs in culture for single-cell
      analysis. CSCs in monolayer cell culture failed to show a circadian rhythm in
      nuclear localization of mPER2 protein, suggesting that cell interactions or the
      tumor-like microenvironment within tumorspheres enable circadian timing. 

PMID- 24333738
TI  - p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in
      response to chemotherapeutic agents.
AB  - The Mitogen Activated Protein Kinase (MAPK) signaling plays a critical role in
      the outcome and the sensitivity to anticancer therapies. Activated MAPK can
      transmit extracellular signals to regulate cell growth, proliferation,
      differentiation, migration, apoptosis and so on. Apoptosis as well as
      macroautophagy (hereafter referred to as autophagy) can be induced by
      extracellular stimuli such the treatment of chemotherapeutic agents, resulting in
      different cell response to these drugs. However, the molecular mechanisms
      mediating these two cellular processes remain largely unknown. Recently, several
      studies provide new insights into p38 and JNK MAPK pathways function in the
      control of the balance of autophagy and apoptosis in response to genotoxic
      stress. Our increased understanding of the role of p38 and JNK MAPK pathways in
      regulating the balance of autophagy and apoptosis will hopefully provide
      prospective strategies for cancer therapy.

PMID- 24333740
TI  - Novel indication for bioabsorbable scaffolds in metal allergy.

PMID- 24333741
TI  - Chronic neck pain and exercise interventions: frequency, intensity, time, and
      type principle.
AB  - OBJECTIVE: To identify the most effective components in an active exercise
      physiotherapy treatment intervention for chronic neck pain based on the
      frequency, intensity, time, and type (FITT) exercise method of tailoring physical
      activity recommendations to the individual needs and goals of patients. DATA
      SOURCES: Databases, including the Allied and Complementary Medicine Database,
      Cumulative Index to Nursing and Allied Health, MEDLINE, SPORTDiscus, Biomedical
      Reference Collection, and Academic Search Premier, were searched for relevant
      articles. STUDY SELECTION: Quantitative design studies that included active
      exercise as part of a multimodal or stand-alone approach were selected. Only
      studies scoring >=6 on the Physiotherapy Evidence Database Scale were included in
      the review because this reflected a good level of evidence. DATA EXTRACTION:
      Study methodologies and relevant outcome measures, including isometric strength,
      Neck Disability Index scores, and pain scores, were extracted from relevant
      articles and grouped together for appraisal and synthesis. DATA SYNTHESIS:
      Evidence from selected articles was synthesized according to the FITT exercise
      principal to determine the most effective exercise type, frequency, and intensity
      in the treatment of chronic neck pain. CONCLUSIONS: Physiotherapy interventions
      using a multimodal approach appear to produce more beneficial outcomes in terms
      of increased strength, improved function, and health-related quality of life and
      reduced pain scores. Active strengthening exercises appear to be beneficial for
      all of these outcomes; the inclusion of additional stretching and aerobic
      exercise components appear to enhance the benefits of an exercise intervention.

PMID- 24333742
TI  - Greenhouse gas emissions of alternative pavement designs: framework development
      and illustrative application.
AB  - Pavement rehabilitation is carbon intensive and the choice of pavement type is a
      critical factor in controlling greenhouse gas (GHG) emissions. The existing body
      of knowledge is not able to support decision-making on pavement choice due to a
      lack of consensus on the system boundaries, the functional units and the
      estimation periods. Excessive data requirements further inhibit the
      generalization of the existing methodologies for design evaluation at the early
      planning stage. This study proposes a practical life-cycle GHG estimation
      approach, which is arguably effective to benchmark pavement emissions given
      project bid tabulation. A set of case studies conducted for this study suggest
      that recycled asphalt pavement (e.g., foam stabilized base (FSB), and warm mix
      asphalt (WMA)) would prevent up to 50% of GHGs from the initial construction
      phase. However, from a life-cycle perspective, pavement emissions are dictated
      largely by the traffic characteristics and the analysis period for the use phase.
      The benefits from using recycled materials (e.g., FSB) are likely to diminish if
      the recycled products do not perform as well as those properly proportioned with
      less recycled materials, or if the recycled materials are locally unavailable.
      When the AADT reaches 10,000, use phase releases more than 97% of the life cycle
      emissions and the emissions difference among alternative designs will be within
      1%. 

PMID- 24333743
TI  - The role of prescribed burn associations in the application of prescribed fires
      in rangeland ecosystems.
AB  - Risk and liability concerns regarding fire affect people's attitudes toward fire
      and have led to human-induced alterations of fire regimes. This has, in turn,
      contributed to brush encroachment and degradation of many grasslands and
      savannas. Efforts to successfully restore such degraded ecosystems at the
      landscape scale in regions of the United States with high proportions of private
      lands require the reintroduction of fire. Prescribed Burn Associations (PBA)
      provide training, equipment, and labor to apply fire safely, facilitating the
      application of this rangeland management tool and thereby reducing the associated
      risk. PBAs help build networks and social capital among landowners who are
      interested in using fire. They can also change attitudes toward fire and enhance
      the social acceptability of using prescribed fire as a management practice. PBAs
      are an effective mechanism for promoting the widespread use of prescribed fire to
      restore and maintain the biophysical integrity of grasslands and savannas at the
      landscape scale. We report findings of a project aimed at determining the human
      dimensions of using prescribed fire to control woody plant encroachment in three
      different eco-regions of Texas. Specifically, we examine membership in PBAs as it
      relates to land manager decisions regarding the use of prescribed fire. Perceived
      risk has previously been identified as a key factor inhibiting the use of
      prescribed fire by landowners. Our results show that perceived constraints, due
      to lack of skill, knowledge, and access to equipment and membership in a PBAs are
      more important factors than risk perceptions in affecting landowner decisions
      about the use of fire. This emphasizes the potential for PBAs to reduce risk
      perceptions regarding the application of prescribed fire and, therefore, their
      importance for restoring brush-encroached grasslands and savannas. 

PMID- 24333744
TI  - Soil plant interactions of Populus alba in contrasting environments.
AB  - The effects of the Populus alba tree on different biochemical soil properties,
      growing in a contaminated area, were studied for two years under field
      conditions. Two types of trace element contaminated soils were studied: a neutral
      contaminated soil (NC) and an acid contaminated soil (AC). One neutral non
      contaminated area was studied as control. Soil samples were collected at depths
      of 0-20 cm and 20-40 cm. Leaves and litter samples were analysed. The addition of
      organic matter, through root exudates and litter, contributed to an increase in
      soil pH, especially in acid soil. Microbial Biomass Carbon (MBC) was
      significantly increased by the presence of the trees in all studied areas,
      especially in the upper soil layer. Similar results were also observed for
      protease activity. Both MBC and Protease activity were more sensitive to
      contamination than beta-glucosidase activity. These changes resulted in a
      decrease of available trace element concentrations in soil and in an improvement
      of soil quality after a 2-year study. The total concentration of Cd and Zn in
      soil did not increase over time due to litter deposition. Analysis of P. alba
      leaves did not show a significant nutritional imbalance and trace element
      concentrations were normal for plants, except for Cd and Zn. These results
      indicate that P. alba is suitable for the improvement of soil quality in riparian
      contaminated areas. However, due to the high Cd and Zn concentrations in leaves,
      further monitoring of this area is required. 

PMID- 24333746
TI  - Mono(pyridine-N-oxide) DOTA analog and its G1/G4-PAMAM dendrimer conjugates
      labeled with 177Lu: radiolabeling and biodistribution studies.
AB  - (177)Lu radiolabeling of the first (G1-) or fourth (G4-) generation
      polyaminoamide (PAMAM) dendrimer conjugates with DOTA-like bifunctional chelator
      with one methylenepyridine-N-oxide pendant arm (DO3A-py(NO-C)) stability of the
      radiolabeled species and their pharmacokinetic characteristics were evaluated in
      preclinical experiments. The results showed that the G1- and G4-dendrimer
      conjugates, modified in average with 7.5 or 57 DO3A-py(NO-C) chelating units,
      respectively, can also be labeled with (177)Lu with a high specific activity and
      radiochemical purity even at 37  degrees C. The radiolabeled species were stable
      for at least 24h. Distribution profile of G1-dendrimer conjugate in organs and
      tissues of rats was more favorable than that of G4 one. On the other hand, the
      later dendrimer conjugate bears a substantially higher number of metal chelators
      per molecule enabling binding of a considerably larger number of radiometals. Our
      results indicate that an employment of dendrimer-chelate conjugates with bound
      radiometals might represent a prospective way for radiolabeling of biologically
      active target-specific macromolecules to obtain markedly high specific activity.

PMID- 24333747
TI  - Comment on "Multielemental analyses of isomorphous Indian garnet gemstones by XRD
      and external pixe techniques" by Venkateswarulu et al. [Appl. Radiat. Isot. 70
      (2012) 2746-2754].

PMID- 24333745
TI  - Auditory event-related potentials and alpha oscillations in the psychosis
      prodrome: neuronal generator patterns during a novelty oddball task.
AB  - Prior research suggests that event-related potentials (ERP) obtained during
      active and passive auditory paradigms, which have demonstrated abnormal
      neurocognitive function in schizophrenia, may provide helpful tools in predicting
      transition to psychosis. In addition to ERP measures, reduced modulations of EEG
      alpha, reflecting top-down control required to inhibit irrelevant information,
      have revealed attentional deficits in schizophrenia and its prodromal stage.
      Employing a three-stimulus novelty oddball task, nose-referenced 48-channel ERPs
      were recorded from 22 clinical high-risk (CHR) patients and 20 healthy controls
      detecting target tones (12% probability, 500Hz; button press) among nontargets
      (76%, 350Hz) and novel sounds (12%). After current source density (CSD)
      transformation of EEG epochs (-200 to 1000ms), event-related spectral
      perturbations were obtained for each site up to 30Hz and 800ms after stimulus
      onset, and simplified by unrestricted time-frequency (TF) principal components
      analysis (PCA). Alpha event-related desynchronization (ERD) as measured by TF
      factor 610-9 (spectral peak latency at 610ms and 9Hz; 31.9% variance) was
      prominent over right posterior regions for targets, and markedly reduced in CHR
      patients compared to controls, particularly in three patients who later developed
      psychosis. In contrast, low-frequency event-related synchronization (ERS)
      distinctly linked to novels (260-1; 16.0%; mid-frontal) and N1 sink across
      conditions (130-1; 3.4%; centro-temporoparietal) did not differ between groups.
      Analogous time-domain CSD-ERP measures (temporal PCA), consisting of N1 sink,
      novelty mismatch negativity (MMN), novelty vertex source, novelty P3, P3b, and
      frontal response negativity, were robust and closely comparable between groups.
      Novelty MMN at FCz was, however, absent in the three converters. In agreement
      with prior findings, alpha ERD and MMN may hold particular promise for predicting
      transition to psychosis among CHR patients. 

PMID- 24333748
TI  - [Feasibility and relevance of an operating room safety checklist for developing
      countries: Study in a French hospital in Djibouti].
AB  - INTRODUCTION: The use of the World Health Organization surgical safety checklist,
      mandatory in operating rooms (OR) in France, significantly reduces morbidity and
      mortality. Our objective was to evaluate the use of this checklist in the OR of a
      French military hospital in Djibouti (Horn of Africa). METHODS: The study was
      performed in three stages: a retrospective evaluation of the checklist use over
      the previous two months, to assess the utilization and completeness rates;
      provision of information to the OR staff; and thereafter, prospective evaluation
      for a one-month period of checklist use, the reasons for non-compliance, and the
      cases in which the checklist identified errors and thus prevented serious adverse
      events. RESULTS: The initial utilization rate was 49%, with only 24% complete.
      After staff training and during the study these rates reached 100% and 99%. The
      staff encountered language difficulties in 53% of cases, and an interpreter was
      available for 81% of them. The capacity of the surgical safety checklist to
      detect serious adverse events was highlighted. CONCLUSION: The utilization and
      completeness rates were initially worse than those observed in metropolitan
      French ORs, but a simple staff information program was rapidly effective.
      Language difficulties are frequent but an interpreter is often available, unlike
      in developed countries where language problems are uncommon and the availability
      of interpreters difficult. Moreover, this study illustrates the ability of the
      checklist to detect and therefore prevent potentially serious adverse events.

PMID- 24333749
TI  - Serial profile of vitamins and trace elements during the acute phase of
      allogeneic stem cell transplantation.
AB  - Currently, we utilize vitamins and trace elements formulations that are not
      prepared specifically for patients receiving hematopoietic stem cell
      transplantation (HSCT), and adequacy of this strategy has not been evaluated. We
      prospectively measured blood level of vitamins and trace elements in 15 patients
      once per week at 6 time points around the acute phase of allogeneic HSCT. We
      provided standard nutrition support, including administration of parenteral
      nutrition with vitamin and trace elements formulation in case of impairment of
      oral intake. Most patients had vitamin B1 deficiency from the start of
      preparative regimens. Vitamin C deficiency was prominent throughout the acute
      phase of HSCT and this was significantly associated with high inflammatory
      markers, C-reactive protein and ferritin. Remarkable vitamin K overload
      associated with administration of parenteral supplementation and ferritin
      overload caused by repeated transfusions was observed. Moderate deficiency of
      zinc was at least partially linked to gastrointestinal loss by diarrhea. We
      revealed several features of vitamin and trace element status in the acute phase
      of HSCT and provided a basis for attempts to improve the nutritional condition in
      HSCT recipients. 

PMID- 24333751
TI  - Covert visual search within and beyond the effective oculomotor range.
AB  - Covert spatial attention is tightly coupled to the eye-movement system, but the
      precise nature of this coupling remains contentious. Recent research has argued
      that covert attention and overt eye-movements many share a common biological
      limit, such that covert exogenous orienting of attention is limited to stimuli
      that fall within the range of possible eye movements (the effective oculomotor
      range: EOMR). However, this conclusion is based on a single experimental
      paradigm: The Posner cueing task. Here, we examine the extent to which covert
      spatial attention is limited to the EOMR in visual search. Exogenous attention
      was assessed using a feature search task and endogenous attention assessed using
      a conjunction search task. The tasks were performed monocularly with the dominant
      eye in the frontal position or abducted by 40 degrees . In the abducted position
      stimuli in the temporal hemispace could be seen, but could not become the goal of
      a saccadic eye-movement (i.e. they were beyond the EOMR). In contrast, stimuli in
      the nasal hemifield remained within the EOMR. We observed a significant effect of
      eye-abduction on feature search, such that search was slower when targets
      appeared beyond the EOMR. In contrast, eye-abduction had no effect on search
      times during conjunction search. Set size did not interact with target location
      or eye-position. It is concluded that optimal covert orienting of exogenous
      attention in visual search is restricted to locations within the effective
      oculomotor range. 

PMID- 24333750
TI  - Single-unit cord blood transplantation after granulocyte colony-stimulating
      factor-combined myeloablative conditioning for myeloid malignancies not in
      remission.
AB  - High disease burden in myeloablative allogeneic hematopoietic stem cell
      transplantation is associated with adverse outcomes in patients with acute
      myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Quiescent leukemia
      stem cells could be induced to enter cell cycle by granulocyte colony-stimulating
      factor (G-CSF) administration and become more susceptible to chemotherapy. We
      report on the outcome of unrelated cord blood transplantation (CBT) using a
      conditioning regimen of 12 Gy total body irradiation, G-CSF-combined high-dose
      cytarabine, and cyclophosphamide in 61 adult patients with AML or advanced MDS
      not in remission. With a median follow-up of 97 months, the probability of
      overall survival and cumulative incidence of relapse at 7 years were 61.4% and
      30.5%, respectively. In multivariate analysis, poor-risk cytogenetics and high
      lactate dehydrogenase values at CBT were independently associated with inferior
      survival. These data demonstrate that CBT after G-CSF-combined myeloablative
      conditioning is a promising curative option for patients with myeloid
      malignancies not in remission. 

PMID- 24333752
TI  - Key issues in decomposing fMRI during naturalistic and continuous music
      experience with independent component analysis.
AB  - BACKGROUND: Independent component analysis (ICA) has been often used to decompose
      fMRI data mostly for the resting-state, block and event-related designs due to
      its outstanding advantage. For fMRI data during free-listening experiences, only
      a few exploratory studies applied ICA. NEW METHOD: For processing the fMRI data
      elicited by 512-s modern tango, a FFT based band-pass filter was used to further
      pre-process the fMRI data to remove sources of no interest and noise. Then, a
      fast model order selection method was applied to estimate the number of sources.
      Next, both individual ICA and group ICA were performed. Subsequently, ICA
      components whose temporal courses were significantly correlated with musical
      features were selected. Finally, for individual ICA, common components across
      majority of participants were found by diffusion map and spectral clustering.
      RESULTS: The extracted spatial maps (by the new ICA approach) common across most
      participants evidenced slightly right-lateralized activity within and surrounding
      the auditory cortices. Meanwhile, they were found associated with the musical
      features. COMPARISON WITH EXISTING METHOD(S): Compared with the conventional ICA
      approach, more participants were found to have the common spatial maps extracted
      by the new ICA approach. Conventional model order selection methods
      underestimated the true number of sources in the conventionally pre-processed
      fMRI data for the individual ICA. CONCLUSIONS: Pre-processing the fMRI data by
      using a reasonable band-pass digital filter can greatly benefit the following
      model order selection and ICA with fMRI data by naturalistic paradigms. Diffusion
      map and spectral clustering are straightforward tools to find common ICA spatial
      maps.

PMID- 24333753
TI  - Brain-machine interface control of a manipulator using small-world neural network
      and shared control strategy.
AB  - The improvement of the resolution of brain signal and the ability to control
      external device has been the most important goal in BMI research field. This
      paper describes a non-invasive brain-actuated manipulator experiment, which
      defined a paradigm for the motion control of a serial manipulator based on motor
      imagery and shared control. The techniques of component selection, spatial
      filtering and classification of motor imagery were involved. Small-world neural
      network (SWNN) was used to classify five brain states. To verify the
      effectiveness of the proposed classifier, we replace the SWNN classifier by a
      radial basis function (RBF) networks neural network, a standard multi-layered
      feed-forward backpropagation network (SMN) and a multi-SVM classifier, with the
      same features for the classification. The results also indicate that the proposed
      classifier achieves a 3.83% improvement over the best results of other
      classifiers. We proposed a shared control method consisting of two control
      patterns to expand the control of BMI from the software angle. The job of path
      building for reaching the 'end' point was designated as an assessment task. We
      recorded all paths contributed by subjects and picked up relevant parameters as
      evaluation coefficients. With the assistance of two control patterns and series
      of machine learning algorithms, the proposed BMI originally achieved the motion
      control of a manipulator in the whole workspace. According to experimental
      results, we confirmed the feasibility of the proposed BMI method for 3D motion
      control of a manipulator using EEG during motor imagery. 

PMID- 24333754
TI  - Comparison of PCR-based diagnoses for visceral leishmaniasis in Bangladesh.
AB  - The diagnosis of visceral leishmaniasis (VL) is performed using multiple methods
      encompassing parasitological, serological and nucleic acid-based diagnostic
      tools, each method with its own unique advantages and disadvantages. Conventional
      parasitological methods are risky for the patient and require skilled personnel
      to collect specimens from spleen or bone marrow, and hence they are not generally
      available in impoverished areas. Polymerase chain reaction (PCR) has been
      validated as an excellent alternative to microscopy in terms of sensitivity and
      specificity. Here, we evaluate four different PCR assays targeting ITS1, ITS2,
      mini-exon and small subunit-rRNA (SSUrRNA) using DNA extracted from peripheral
      blood buffy coat in order to avoid more invasive processes. A total of 61 VL
      patients and 75 non-VL infected control individuals were enrolled. The VL
      patients were confirmed to be positive for Leishmania amastigotes in splenic
      smears by microscopy. Sensitivities of the PCR targeting ITS1, ITS2, SSUrRNA and
      mini-exon were 96.7%, 91.8%, 88.5% and 34.4%, respectively, while the specificity
      was 98.7% for all methods. Nested PCR for ITS1 resulted in 100% sensitivity. The
      efficacy of each PCR was evaluated with various Leishmania amastigote parasite
      loads in each spleen smear, graded from 1+ to 5+. The PCR targeting ITS1 showed
      100% sensitivity for the detection of Leishmania donovani in all samples from
      grades >=3, >=4, and >=5, respectively. The restriction fragment length
      polymorphism observed in ITS1 amplicons digested by HaeIII classified the
      parasite into L. donovani complex. The ITS1 PCR was found to be equal to
      conventional, but very invasive and risky parasitological diagnoses and superior
      to other PCR based methods in sensitivity and examination of genetic
      heterogeneity. We recommend the PCR targeting ITS1 using peripheral blood buffy
      coat DNA as an alternate, less invasive diagnostic choice for the confirmation of
      L. donovani infection. 

PMID- 24333755
TI  - The involvement of heparin in retinal infection by Toxoplasma gondii in a chick
      model revealed an ontogenetic-dependent pattern.
AB  - This work aimed to test the influence of heparin on the susceptibility of retinal
      cells to Toxoplasma gondii infection. Primary cultures of retinas from chick
      embryos of 8 (E8) or 11 (E11) days and fibroblasts (control) were used. To
      determine the influence of heparin in T. gondii infection, tachyzoites of the RH
      strain were treated with heparin before addition in the culture. A monoclonal
      anti-heparin antibody was used to analyze the heparin distribution on fibroblast
      and retinal cell surfaces. Our results showed that retinal cells (E8 and E11) had
      a higher infection rate than fibroblasts (91% and 24% versus 13%, respectively).
      Pre-treatment of T. gondii with heparin decreased infection of E8 retinal cells
      when compared with non-treated parasites (45% versus 91%, respectively), but not
      of E11 cells (35% versus 48%). In accordance, retinal cells presented an intense
      heparin staining by immunofluorescence assay. In conclusion, retinal cells from
      chick embryos were more susceptible to infection by T. gondii compared to
      fibroblasts and, pre-treatment of tachyzoites with heparin decreased the number
      of infected cells and parasite burden particularly for E8 retinal cells. 

PMID- 24333756
TI  - The Tim-3/galectin-9 pathway involves in the homeostasis of hepatic Tregs in a
      mouse model of concanavalin A-induced hepatitis.
AB  - T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is a
      negative regulator of interferon (IFN)-gamma-secreting CD4(+) Th1 cells and plays
      a key role in autoimmune diseases. Here, we report that galectin-9 expression was
      increased in hepatic CD4(+)CD25(+) T cells in a mouse model of concanavalin A
      (Con A)-induced hepatitis. Moreover, Tim-3 showed increased levels in
      CD4(+)CD25(+) Foxp3(+) regulatory T cells (Tregs). Further analyses showed that
      blocking the Tim-3/galectin-9 pathway resulted in the suppression of Tregs in
      vitro, thereby significantly increasing interferon (IFN)-gamma production from
      hepatic Teffs. Moreover, blockade of Tim-3 in vivo with an anti-Tim-3 antibody
      exacerbated the acute hepatitis, possibly by increased IFN-gamma production.
      Furthermore, we found that in vitro activation of CD4(+)CD25(-) T cells with the
      T cell receptor (TCR) plus interleukin 2 (IL-2) up-regulated Tim-3 expression.
      And the induced Tim-3 interacted with galectin-9 to induce CD4(+) T cell
      apoptosis which could be partly reversed by blocking Tim-3 signaling. Our results
      suggested that the Tim-3/galectin-9 pathway plays a critical role in the
      homeostasis of hepatic Tregs through the elimination induction in Teffs and the
      inhibition of IFN-gamma release, which contributes to the pathogenesis of liver
      damage and constitutes at least part of the mechanism underlying the induction of
      hepatitis by Con A. 

PMID- 24333757
TI  - Structural characterization of the main immunogenic region of the Torpedo
      acetylcholine receptor.
AB  - To develop antigen-specific immunotherapies for autoimmune diseases, knowledge of
      the molecular structure of targeted immunological hotspots will guide the
      production of reagents to inhibit and halt production of antigen specific attack
      agents. To this end we have identified three noncontiguous segments of the
      Torpedo nicotinic acetylcholine receptor (AChR) alpha-subunit that contribute to
      the conformationally sensitive immunological hotspot on the AChR termed the main
      immunogenic region (MIR): alpha(1-12), alpha(65-79), and alpha(110-115). This
      region is the target of greater than 50% of the anti-AChR Abs in serum from
      patients with myasthenia gravis (MG) and animals with experimental autoimmune
      myasthenia gravis (EAMG). Many monoclonal antibodies (mAbs) raised in one species
      against an electric organ AChR cross react with the neuromuscular AChR MIR in
      several species. Probing the Torpedo AChR alpha-subunit with mAb 132A, a disease
      inducing anti-MIR mAb raised against the Torpedo AChR, we have determined that
      two of the three MIR segments, alpha(1-12) and alpha(65-79), form a complex
      providing the signature components recognized by mAb 132A. These two segments
      straddle a third, alpha(110-115), that seems not to contribute specific side
      chains for 132A recognition, but is necessary for optimum antibody binding. This
      third segment appears to form a foundation upon which the three-dimensional 132A
      epitope is anchored. 

PMID- 24333758
TI  - Chronic inflammation and extra-nodal marginal-zone lymphomas of MALT-type.
AB  - Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT) is
      an indolent B-cell non-Hodgkin lymphoma (NHL) arising in lymphoid populations
      that are induced by chronic inflammation in extra nodal sites. The stomach is the
      most commonly affected organ, and MALT lymphoma is clearly associated with a
      gastroduodenitis induced by a microbial pathogen, Helicobacter pylori, thus
      gastric MALT lymphoma represents a paradigm for evaluating inflammatory
      associated lymphomagenesis. Variable levels of evidence have indicated a possible
      association between other microorganisms and non-gastric MALT lymphomas. In
      addition to infectious etiology, chronic inflammation arising as a result of
      autoimmune diseases such as Sjogren's syndrome or Hashimoto thyroiditis, poses a
      significant risk factor for developing NHL. Recently, genetic alterations
      affecting the NF-kappaB pathway, a major signaling pathway involved in many
      cancers, have been identified in MALT lymphoma. This review will present MALT
      lymphoma as an example of the close pathogenetic link between chronic
      microenvironmental inflammation and tumor development, showing how these
      observations can be integrated into daily clinical practice, also in terms of
      therapeutic implications, with particular focus on the NF-kappaB pathway. 

PMID- 24333759
TI  - Lymphoma development in patients with autoimmune and inflammatory disorders--what
      are the driving forces?
AB  - For decades, it has been known that patients with certain autoimmune and
      inflammatory disorders, such as rheumatoid arthritis (RA) and primary Sjogren's
      syndrome (pSS), have an increased risk of developing malignant lymphoma. Although
      the clinico-biological reasons for this association remain largely unknown, our
      knowledge has improved and new insights have been obtained. First, the direct
      link between autoimmunity and lymphomagenesis has been strengthened by large
      epidemiological studies showing a consistent risk increase of lymphoma associated
      with certain autoimmune/inflammatory conditions in independent cohorts from
      different countries. Second, a number of local and systemic disease-related risk
      factors in these diseases have been repeatedly linked to lymphoma development,
      with the prime examples being disease severity and the degree of inflammatory
      activity. Considering the key role of B- and T-cell activation in the
      pathogenesis of both autoimmunity and lymphoma, it is perhaps not surprising that
      longstanding chronic inflammation and/or antigen stimulation have emerged as
      major predisposing factors of lymphoma in patients with active autoimmune
      disease. Finally, increasing evidence suggests that lymphomas associated with
      autoimmunity constitute a different spectrum of entities compared to lymphomas
      arising in patients without any known autoimmune or inflammatory conditions,
      pointing to a different pathobiology. In this review, we summarize the recent
      literature that supports a direct or indirect link between immune-mediated
      disease and lymphoma and describe the characteristics of lymphomas developing in
      the different diseases. We also discuss molecular, genetic and microenvironmental
      factors that may come into play in the pathobiology of these disorders. 

PMID- 24333760
TI  - Acridine orange leukocyte fluorography in mice.
AB  - Simultaneous non-invasive visualization of blood vessels and nerves in patients
      can be obtained in the eye. The retinal vasculature is a target of many
      retinopathies. Inflammation, readily manifest by leukocyte adhesion to the
      endothelial lining, is a key pathophysiological mechanism of many retinopathies,
      making it a valuable and ubiquitous target for disease research. Leukocyte
      fluorography has been extensively used in the past twenty years; however,
      fluorescent markers, visualization techniques, and recording methods have
      differed between studies. The lack of detailed protocol papers regarding
      leukocyte fluorography, coupled with lack of uniformity between studies, has led
      to a paucity of standards for leukocyte transit (velocity, adherence,
      extravasation) in the retina. Here, we give a detailed description of a
      convenient method using acridine orange (AO) and a commercially available
      scanning laser ophthalmoscope (SLO, HRA-OCT Spectralis) to view leukocyte
      behavior in the mouse retina. Normal mice are compared to mice with acute and
      chronic inflammation. This method can be readily adopted in many research labs. 

PMID- 24333761
TI  - Strain dependent UV degradation of Escherichia coli DNA monitored by Fourier
      transform infrared spectroscopy.
AB  - In this work we present a method for detection of DNA isolated from nonpathogenic
      Escherichia coli strains, respectively. Untreated and UV irradiated bacterial
      DNAs were analyzed by FT-IR spectroscopy, to investigate their screening
      characteristic features and their structural radiotolerance at 253.7nm. FT-IR
      spectra, providing a high molecular structural information, have been analyzed in
      the wavenumber range 800-1800cm(-1). FT-IR signatures, spectroscopic band
      assignments and structural interpretations of these DNAs are reported. Also, UV
      damage at the DNA molecular level is of interest. Strain dependent UV degradation
      of DNA from E. coli has been observed. Particularly, alterations in nucleic acid
      bases, base pairing and base stacking have been found. Also changes in the DNA
      conformation and deoxyribose were detected. Based on this work, specific E. coli
      DNA-ligand interactions, drug development and vaccine design for a better
      understanding of the infection mechanism caused by an interference between
      pathogenic and nonpathogenic bacteria and for a better control of disease,
      respectively, might be further investigated using Fourier transform infrared
      spectroscopy. Besides, understanding the pathways for UV damaged DNA response,
      like nucleic acids repair mechanisms is appreciated. 

PMID- 24333762
TI  - Expression of genes in normal fibroblast cells (WS1) in response to irradiation
      at 660nm.
AB  - Photobiomodulation has been found to increase gene expression and release of
      various growth factors and cytokines involved in wound healing.
      Photobiomodulation has been used to treat a wide variety of disorders, and has
      been found to be beneficial in the treatment of chronic wounds, however the exact
      underlying mechanism is not well understood. This study aimed to profile 84genes
      in response to irradiation at 660nm. WS1 human skin fibroblasts were used in gene
      expression profiling studies in response to irradiation with a 660nm diode laser
      at a fluence of 5J/cm(2) and power density of 11mW/cm(2). Forty-eight hours post
      irradiation, 1MUg RNA was reverse transcribed and used in real-time qualitative
      polymerase chain reaction (qPCR). Genes involved in the extracellular matrix and
      cell adhesion, inflammatory cytokines and chemokines, growth factors and signal
      transduction were evaluated. A total of 76genes were regulated by laser
      irradiation, 43genes were up-regulated while 33genes were down-regulated.
      Irradiation of WS1 cells at 660nm modulates the expression of genes involved in
      collagen production, cellular adhesion, remodelling and spreading, the
      cytoskeleton, inflammatory cytokines and chemokines, growth factors and molecules
      involved in signal transduction. 

PMID- 24333763
TI  - Fluorescence spectroscopic characterization of salivary metabolites of oral
      cancer patients.
AB  - A pilot study has been carried out using human saliva in differentiating the
      normal subjects from that of oral squamous cell carcinoma (OSCC) patients, using
      the autofluorescence spectroscopy at 405nm excitation. A markable difference in
      the spectral signatures between the saliva of normal subjects and that of oral
      cancer patients has been noticed. The possible reasons for the altered spectral
      signature may be due to the presence of endogenous porphyrin, NAD(P)H and FAD in
      the exfoliated cells from saliva. The elevated level of porphyrin in saliva of
      OSCC patients may be attributed to the disturbances in the amino acid degradation
      pathway and heme biosynthetic pathway, during the transformation of normal into
      malignant cells. The integrated area under the curve of fluorescence emission
      spectrum at 405nm excitation and also fluorescence excitation spectrum for 625nm
      emission were compared for the saliva of normal and oral cancer patients. The
      area under the curve for the emission spectrum provides 85.7% sensitivity and
      93.3% specificity, where as the fluorescence excitation spectrum discriminates
      the same with 84.1% sensitivity and 93.2% specificity. 

PMID- 24333764
TI  - Preparation and characterization of mTHPC-loaded solid lipid nanoparticles for
      photodynamic therapy.
AB  - Among various attempts to enhance the therapeutic efficacy of photodynamic
      therapy (PDT), the specific delivery of photosensitizer (PS) in the tumor tissue
      is expected to improve its clinical applications. The aim of this study was to
      engineer lipid nanoparticles (LNP) with different sizes and various PS contents,
      using simple solvent-free and easily scale up manufacturing processes. Meso
      (tetrahydroxyphenyl) chlorin (mTHPC) is one of the most potent photoactive
      compounds for clinical use. We demonstrated that mTHPC was efficiently
      incorporated into the lipid core of LNP, leading to a large range of stable and
      reproducible mTHPC-loaded LNP with narrow size distribution. Photophysical and
      physico-chemical properties of mTHPC-loaded LNP were assessed as well as
      absorption spectra and singlet oxygen emission, colloidal stability, particle
      size and zeta potential. The photocytotoxicity of selected mTHPC-loaded solid LNP
      was demonstrated on MCF-7 cells under irradiation at 652nm with a range of light
      fluence from 1.0 to 10J/cm(2). All physico-chemical, photophysical and biological
      results allow us to conclude that solid LNP appear as a very promising nano-mTHPC
      delivery system for PDT. 

PMID- 24333765
TI  - Enantiomeric in vitro DNA binding, pBR322 DNA cleavage and molecular docking
      studies of chiral L- and D-ternary copper(II) complexes of histidine and
      picolinic acid.
AB  - Novel chiral ternary Cu(II) and Ni(II) complexes of l/d-histidine and picolinic
      acid, 1 and 2(a and b) were synthesized and characterized by elemental analysis,
      molar conductance and spectroscopic data (IR, NMR, EPR, UV-vis). In vitro DNA
      binding profile of both Cu(II) and Ni(II) complexes have been investigated by UV
      vis titrations, while fluorescence spectroscopy, circular dichroism and viscosity
      measurements were carried out for Cu(II) complexes 1(a and b). Both the
      enantiomers of 1 and 2(a and b) bind to CT DNA via electrostatic interactions and
      the intrinsic binding constant, Kb values for complexes 1 and 2(a and b) were
      found to be 5.6*10(4), 9.8*10(3), 8.2*10(3) and 6.7*10(3)M(-1), respectively
      suggesting greater binding propensity of l-form of Cu(II) complex 1a. The DNA
      cleavage activity of complexes 1(a and b), investigated by agarose gel
      electrophoresis suggested an oxidative pathway for DNA cleavage. Further, the
      molecular docking studies of complexes 1(a and b) were carried out with B-DNA
      revealing that the complexes bind to the adenine-thymine residues in the minor
      groove of the DNA. The resulting binding energies of docked metal complexes 1(a
      and b) were found to be -265.1 and -218.9KJmol(-1), respectively. Furthermore,
      enantiomeric complexes 1 and 2(a and b) were screened for in vitro antimicrobial
      activity. 

PMID- 24333766
TI  - Synthesis, characterization, DNA-binding studies and acetylcholinesterase
      inhibition activity of new 3-formyl chromone derivatives.
AB  - A series of new substituted 3-formyl chromone derivatives (4-6) were synthesized
      by one step reaction methodology by knoevenagel condensation, structurally
      similar to known bisintercalators. The new compounds were characterized by IR,
      (1)H NMR, (13)C NMR, MS and analytical data. The in vitro DNA binding profile of
      compounds (4-6) was carried out by absorption, fluorescence and viscosity
      measurements. It was found that synthesized compounds, especially compound 6
      (evident from binding constant value) bind strongly with calf thymus DNA,
      presumably via an intercalation mode. Additionally, molecular docking studies of
      compounds (4-6) were carried out with B-DNA (PDBID: 1BNA) which revealed that
      partial intercalative mode of mechanism is operational in synthesized compounds
      (4-6) with CT-DNA. The binding constants evaluated from fluorescence spectroscopy
      of compounds with CT-DNA follows the order compound 6>compound 5>compound 4. All
      the compounds (4-6) were screened for acetylcholinesterase inhibition assay. It
      can be inferred from data, that compound (6) showed potent AChE inhibition having
      IC50=0.27MUM, almost in vicinity to reference drug Tacrine (IC50=0.19MUM). 

PMID- 24333767
TI  - The effect of uranium migration on radionuclide distributions for soil samples at
      the El-Gor area, Sinai, Egypt.
AB  - The concentrations and distributions of the activity of natural radionuclides in
      soil samples were investigated in fifteen soil samples at El-Gor area
      representing two profiles (A and B) using a HP-Ge detector and alpha counting by
      SSNTD (CR-39), respectively. The average concentrations of the radionuclides
      (238)U, (226)Ra, (235)U, (232)Th and (40)K are 203.4, 177.23, 9.77, 43.33 and
      386.22 Bq kg(-1) (dry weight), respectively, and profile A and (238)U, (226)Ra,
      (235)U, (232)Th and (40)K have average concentrations of 232.58, 246, 11.7, 31.7,
      and 277.07 Bq kg(-1) for profile B, respectively. The eTh and eU were estimated
      to detect the migration process of uranium into or out of an area or uranium to
      or from the studied profiles. The results indicate a migration of uranium by 29%
      for profile A and 65.37% for profile B. The activity ratio ((238)U/(226)Ra) was
      found to be 0.9 in profile A and 1.15 in profile B. These ratios coincide with
      the uranium migration processes. The responsible mass corresponding to the
      measured (226)Ra activity was also calculated. The radon activity concentrations
      for the two profiles are nearly 300 Bq m(-3). The emanation coefficient (eta) was
      calculated from the ratio of the expected radon activity to the measured radon
      for the studied soil samples. The value of eta was found to depend only on the
      radium activity regardless to soil formation.

PMID- 24333769
TI  - Development of a supercritical fluid chromatography-tandem mass spectrometry
      method for the determination of lacidipine in beagle dog plasma and its
      application to a bioavailability study.
AB  - A simple, novel, rapid and sensitive supercritical fluid chromatography-tandem
      mass spectrometry (SFC-MS/MS) method was developed and validated for the
      determination of lacidipine in beagle dog plasma with nimodipine as internal
      standard. The method involved a simple liquid-liquid extraction method with tert
      butyl methyl ether. The analytes were analyzed on an Acquity UPC(2) with a HSS
      C18 SB column (3mm*100mm, 1.8MUm) set at 50 degrees C. The mobile phase was
      carbon dioxide (>=99.99%) and methanol (92:8, v/v) at a flow rate of 2ml/min, the
      compensation solvent was methanol with 2% formic acid at a flow rate of 0.2ml/min
      and a total analysis time of 1.5min for each sample. The multiple reaction
      monitoring mode was used for quantification of ion transitions at m/z 473.32
      >354.10 and 419.00->343.10 for lacidipine and internal standard, respectively.
      The linearity range of proposed method was 0.10-100ng/ml) (r(2)>=0.9990). The
      intra- and inter-day precision values were less than 15% and accuracy was from 
      0.83% to 3.27% at all quality control levels. The proposed method was
      successfully applied to a pharmacokinetic study of lacidipine in beagle dogs. 

PMID- 24333768
TI  - Administration of low dose methamphetamine 12 h after a severe traumatic brain
      injury prevents neurological dysfunction and cognitive impairment in rats.
AB  - We recently published data that showed low dose of methamphetamine is
      neuroprotective when delivered 3 h after a severe traumatic brain injury (TBI).
      In the current study, we further characterized the neuroprotective potential of
      methamphetamine by determining the lowest effective dose, maximum therapeutic
      window, pharmacokinetic profile and gene expression changes associated with
      treatment. Graded doses of methamphetamine were administered to rats beginning 8
      h after severe TBI. We assessed neuroprotection based on neurological severity
      scores, foot fault assessments, cognitive performance in the Morris water maze,
      and histopathology. We defined 0.250 mg/kg/h as the lowest effective dose and
      treatment at 12 h as the therapeutic window following severe TBI. We examined
      gene expression changes following TBI and methamphetamine treatment to further
      define the potential molecular mechanisms of neuroprotection and determined that
      methamphetamine significantly reduced the expression of key pro-inflammatory
      signals. Pharmacokinetic analysis revealed that a 24-hour intravenous infusion of
      methamphetamine at a dose of 0.500 mg/kg/h produced a plasma Cmax value of 25.9
      ng/ml and a total exposure of 544 ng/ml over a 32 hour time frame. This
      represents almost half the 24-hour total exposure predicted for a daily oral dose
      of 25mg in a 70 kg adult human. Thus, we have demonstrated that methamphetamine
      is neuroprotective when delivered up to 12 h after injury at doses that are
      compatible with current FDA approved levels.

PMID- 24333770
TI  - The influence of a bicycle commuter's appearance on drivers' overtaking
      proximities: an on-road test of bicyclist stereotypes, high-visibility clothing
      and safety aids in the United Kingdom.
AB  - This study looked at whether drivers overtaking a bicyclist changed the
      proximities of their passes in response to the level of experience and skill
      signalled by the bicyclist's appearance. Seven outfits were tested, ranging from
      a stereotypical sport rider's outfit, portraying high experience and skill, to a
      vest with 'novice cyclist' printed on the back, portraying low experience. A high
      visibility bicycling jacket was also used, as were two commercially available
      safety vests, one featuring a prominent mention of the word 'police' and a
      warning that the rider was video-recording their journey, and one modelled after
      a police officer's jacket but with a letter changed so it read 'POLITE'. An
      ultrasonic distance sensor recorded the space left by vehicles passing the
      bicyclist on a regular commuting route. 5690 data points fulfilled the criteria
      for the study and were included in the analyses. The only outfit associated with
      a significant change in mean passing proximities was the police/video-recording
      jacket. Contrary to predictions, drivers treated the sports outfit and the
      'novice cyclist' outfit equivalently, suggesting they do not adjust overtaking
      proximity as a function of a rider's perceived experience. Notably, whilst some
      outfits seemed to discourage motorists from passing within 1m of the rider,
      approximately 1-2% of overtakes came within 50 cm no matter what outfit was worn.
      This suggests there is little riders can do, by altering their appearance, to
      prevent the very closest overtakes; it is suggested that infrastructural,
      educational or legal measures are more promising for preventing drivers from
      passing extremely close to bicyclists.

PMID- 24333771
TI  - Dynamic compositional modeling of pedestrian crash counts on urban roads in
      Connecticut.
AB  - Uncovering the temporal trend in crash counts provides a good understanding of
      the context for pedestrian safety. With a rareness of pedestrian crashes it is
      impossible to investigate monthly temporal effects with an individual
      segment/intersection level data, thus the time dependence should be derived from
      the aggregated level data. Most previous studies have used annual data to
      investigate the differences in pedestrian crashes between different regions or
      countries in a given year, and/or to look at time trends of fatal pedestrian
      injuries annually. Use of annual data unfortunately does not provide sufficient
      information on patterns in time trends or seasonal effects. This paper describes
      statistical methods uncovering patterns in monthly pedestrian crashes aggregated
      on urban roads in Connecticut from January 1995 to December 2009. We investigate
      the temporal behavior of injury severity levels, including fatal (K), severe
      injury (A), evident minor injury (B), and non-evident possible injury and
      property damage only (C and O), as proportions of all pedestrian crashes in each
      month, taking into consideration effects of time trend, seasonal variations and
      VMT (vehicle miles traveled). This type of dependent multivariate data is
      characterized by positive components which sum to one, and occurs in several
      applications in science and engineering. We describe a dynamic framework with
      vector autoregressions (VAR) for modeling and predicting compositional time
      series. Combining these predictions with predictions from a univariate
      statistical model for total crash counts will then enable us to predict
      pedestrian crash counts with the different injury severity levels. We compare
      these predictions with those obtained from fitting separate univariate models to
      time series of crash counts at each injury severity level. We also show that the
      dynamic models perform better than the corresponding static models. We implement
      the Integrated Nested Laplace Approximation (INLA) approach to enable fast
      Bayesian posterior computation. Taking CO injury severity level as a baseline for
      the compositional analysis, we conclude that there was a noticeable shift in the
      proportion of pedestrian crashes from injury severity A to B, while the increase
      for injury severity K was extremely small over time. This shift to the less
      severe injury level (from A to B) suggests that the overall safety on urban roads
      in Connecticut is improving. In January and February, there was some increase in
      the proportions for levels A and B over the baseline, indicating a seasonal
      effect. We found evidence that an increase in VMT would result in a decrease of
      proportions over the baseline for all injury severity levels. Our dynamic model
      uncovered a decreasing trend in all pedestrian crash counts before April 2005,
      followed by a noticeable increase and a flattening out until the end of the
      fitting period. This appears to be largely due to the behavior of injury severity
      level A pedestrian crashes.

PMID- 24333772
TI  - Bexarotene nanocrystal-Oral and parenteral formulation development,
      characterization and pharmacokinetic evaluation.
AB  - Bexarotene (Targretin(r)) is a synthetic retinoid that selectively activates the
      retinoid X receptor subfamily of retinoid receptors and exhibits potent anti
      tumor activity. However, the poor solubility and bioavailability limit its
      application. The main aim of this study is to investigate the potential of oral
      and parenteral nanocrystals in enhancing the bioavailability of bexarotene. In
      this work, the orthogonal design was used to screen the optimum stabilizers and
      precipitation-combined microfluidization method was employed to obtain the
      optimal nanocrystals. According to DSC, X-ray diffraction analysis and Raman
      examination, the nanocrystals were still in crystalline state after the
      preparation procedure. By reducing the particle size, the in vitro dissolution
      rate of bexarotene was increased significantly. The in vivo test was carried out
      in rats and pharmacokinetic parameters of the bexarotene solution and bexarotene
      nanocrystals were compared after gavage and intravenous administration. The
      higher AUC and lower Cmax indicated that oral bexarotene nanocrystals
      significantly increased the bioavailability of bexarotene and decreased its side
      effects. Compared to the oral nanocrystals, the intravenous nanocrystals cut
      losses and increased bioavailability because of the absence of first pass effect
      and enterohepatic circulation. 

PMID- 24333773
TI  - Generalization of the Matsumoto-Tonomura approximation for the phase shift within
      an open aperture.
AB  - As shown by Matsumoto and Tonomura, the phase shift imposed on an electron beam
      by an electrostatic phase plate is constant for all (straight) electron
      trajectories passing through a circular aperture, provided that (1) the electric
      field goes to zero at distances far above and below the aperture and (2) the
      value of the phase shift at the boundary (i.e. perimeter of the aperture) is
      constant [5]. We now point out that the result can be valid for any shape of the
      hole in the aperture, and, furthermore, it requires only that the electric field
      is equal and opposite at large distances above and below the aperture,
      respectively. We also point out that the conditions of validity of the Matsumoto
      Tonomura approximation constrain the phase shift across the open aperture to a
      quadratic algebraic form when the phase shift is not constant around the
      perimeter. Finally, it follows that the projection approximation for calculating
      the phase shift must fail for strong phase shifts of higher than quadratic form.
      These extensions of the original result of Matsumoto and Tonomura give further
      insight to the analysis of charging phenomena observed with apertures that are
      designed to produce contrast in in-focus images of weak phase objects. 

PMID- 24333774
TI  - Salivary gland development: a template for regeneration.
AB  - The mammalian salivary gland develops as a highly branched structure designed to
      produce and secrete saliva. This review will focus on research on mouse
      submandibular gland development and the translation of this basic research toward
      therapy for patients suffering from salivary hypofunction. Here we review the
      most recent literature that has enabled a better understanding of the mechanisms
      of salivary gland development. Additionally, we discuss approaches proposed to
      restore salivary function using gene and cell-based therapy. Increasing our
      understanding of the developmental mechanisms involved during development is
      critical to design effective therapies for regeneration and repair of damaged
      glands. 

PMID- 24333776
TI  - Methylprednisolone prevents nerve injury-induced hyperalgesia in neprilysin
      knockout mice.
AB  - The pathophysiology of the complex regional pain syndrome involves enhanced
      neurogenic inflammation mediated by neuropeptides. Neutral endopeptidase
      (neprilysin, NEP) is a key enzyme in neuropeptide catabolism. Our previous work
      revealed that NEP knock out (ko) mice develop more severe hypersensitivity to
      thermal and mechanical stimuli after chronic constriction injury (CCI) of the
      sciatic nerve than wild-type (wt) mice. Because treatment with glucocorticoids is
      effective in early complex regional pain syndrome, we investigated whether
      methylprednisolone (MP) reduces pain and sciatic nerve neuropeptide content in
      NEP ko and wt mice with nerve injury. After CCI, NEP ko mice developed more
      severe thermal and mechanical hypersensitivity and hind paw edema than wt mice,
      confirming previous findings. Hypersensitivity was prevented by MP treatment in
      NEP ko but not in wt mice. MP treatment had no effect on protein levels of
      calcitonin-gene related peptide, substance P, and bradykinin in sciatic nerves of
      NEP ko mice. Endothelin-1 (ET-1) levels were higher in naive and nerve-injured
      NEP ko than in wt mice, without an effect of MP treatment. Gene expression of the
      ET-1 receptors ETAR and ETBR was not different between genotypes and was not
      altered after CCI, but was increased after additional MP treatment. The ETBR
      agonist IRL-1620 was analgesic in NEP ko mice after CCI, and the ETBR antagonist
      BQ-788 showed a trend to reduce the analgesic effect of MP. The results provide
      evidence that MP reduces CCI-induced hyperalgesia in NEP ko mice, and that this
      may be related to ET-1 via analgesic actions of ETBR. 

PMID- 24333777
TI  - BKCa channels expressed in sensory neurons modulate inflammatory pain in mice.
AB  - Large conductance calcium-activated potassium (BKCa) channels are important
      regulators of neuronal excitability. Although there is electrophysiological
      evidence for BKCa channel expression in sensory neurons, their in vivo functions
      in pain processing have not been fully defined. Using a specific antibody, we
      demonstrate here that BKCa channels are expressed in subpopulations of
      peptidergic and nonpeptidergic nociceptors. To test a functional association of
      BKCa channel activity in sensory neurons with particular pain modalities, we
      generated mice in which BKCa channels are ablated specifically from sensory
      neurons and analyzed their behavior in various models of pain. Mutant mice showed
      increased nociceptive behavior in models of persistent inflammatory pain.
      However, their behavior in models of neuropathic or acute nociceptive pain was
      normal. Moreover, systemic administration of the BKCa channel opener, NS1619,
      inhibited persistent inflammatory pain. Our investigations provide in vivo
      evidence that BKCa channels expressed in sensory neurons exert inhibitory control
      on sensory input in inflammatory pain states. 

PMID- 24333775
TI  - Botulinum toxin B in the sensory afferent: transmitter release, spinal
      activation, and pain behavior.
AB  - We addressed the hypothesis that intraplantar botulinum toxin B
      (rimabotulinumtoxin B: BoNT-B) has an early local effect upon peripheral afferent
      terminal releasing function and, over time, will be transported to the central
      terminals of the primary afferent. Once in the terminals it will cleave synaptic
      protein, block spinal afferent transmitter release, and thereby prevent spinal
      nociceptive excitation and behavior. In mice, C57Bl/6 males, intraplantar BoNT-B
      (1 U) given unilaterally into the hind paw had no effect upon survival or motor
      function, but ipsilaterally decreased: (1) intraplantar formalin-evoked
      flinching; (2) intraplantar capsaicin-evoked plasma extravasation in the hind paw
      measured by Evans blue in the paw; (3) intraplantar formalin-evoked dorsal horn
      substance P (SP) release (neurokinin 1 [NK1] receptor internalization); (4)
      intraplantar formalin-evoked dorsal horn neuronal activation (c-fos); (5)
      ipsilateral dorsal root ganglion (DRG) vesicle-associated membrane protein
      (VAMP); (6) ipsilateral SP release otherwise evoked bilaterally by intrathecal
      capsaicin; (7) ipsilateral activation of c-fos otherwise evoked bilaterally by
      intrathecal SP. These results indicate that BoNT-B, after unilateral intraplantar
      delivery, is taken up by the peripheral terminal, is locally active (blocking
      plasma extravasation), is transported to the ipsilateral DRG to cleave VAMP, and
      is acting presynaptically to block release from the spinal peptidergic terminal.
      The observations following intrathecal SP offer evidence for a possible
      transsynaptic effect of intraplantar BoNT. These results provide robust evidence
      that peripheral BoNT-B can alter peripheral and central terminal release from a
      nociceptor and attenuate downstream nociceptive processing via a presynaptic
      effect, with further evidence suggesting a possible postsynaptic effect.

PMID- 24333778
TI  - Pain sensitivity is inversely related to regional grey matter density in the
      brain.
AB  - Pain is a highly personal experience that varies substantially among individuals.
      In search of an anatomical correlate of pain sensitivity, we used voxel-based
      morphometry to investigate the relationship between grey matter density across
      the whole brain and interindividual differences in pain sensitivity in 116
      healthy volunteers (62 women, 54 men). Structural magnetic resonance imaging
      (MRI) and psychophysical data from 10 previous functional MRI studies were used.
      Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location
      were added to the model as covariates. Regression analysis of grey matter density
      across the whole brain and thermal pain intensity ratings at 49 degrees C
      revealed a significant inverse relationship between pain sensitivity and grey
      matter density in bilateral regions of the posterior cingulate cortex, precuneus,
      intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the
      left primary somatosensory cortex also exhibited this inverse relationship. No
      regions showed a positive relationship to pain sensitivity. These structural
      variations occurred in areas associated with the default mode network,
      attentional direction and shifting, as well as somatosensory processing. These
      findings underscore the potential importance of processes related to default mode
      thought and attention in shaping individual differences in pain sensitivity and
      indicate that pain sensitivity can potentially be predicted on the basis of brain
      structure. 

PMID- 24333780
TI  - Placebo analgesia: clinical applications.

PMID- 24333779
TI  - MrgC agonism at central terminals of primary sensory neurons inhibits neuropathic
      pain.
AB  - Chronic neuropathic pain is often refractory to current pharmacotherapies. The
      rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial
      homogeneity with its human homologue, MrgX1, and is located specifically in small
      diameter dorsal root ganglion neurons. However, evidence regarding the role of
      MrgC in chronic pain conditions has been disparate and inconsistent. Accordingly,
      the therapeutic value of MrgX1 as a target for pain treatment in humans remains
      uncertain. Here, we found that intrathecal injection of BAM8-22 (a 15-amino acid
      peptide MrgC agonist) and JHU58 (a novel dipeptide MrgC agonist) inhibited both
      mechanical and heat hypersensitivity in rats after an L5 spinal nerve ligation
      (SNL). Intrathecal JHU58-induced pain inhibition was dose dependent in SNL rats.
      Importantly, drug efficacy was lost in Mrg-cluster gene knockout (Mrg KO) mice
      and was blocked by gene silencing with intrathecal MrgC siRNA and by a selective
      MrgC receptor antagonist in SNL rats, suggesting that the drug action is MrgC
      dependent. Further, in a mouse model of trigeminal neuropathic pain,
      microinjection of JHU58 into ipsilateral subnucleus caudalis inhibited mechanical
      hypersensitivity in wild-type but not Mrg KO mice. Finally, JHU58 attenuated the
      miniature excitatory postsynaptic currents frequency both in medullary dorsal
      horn neurons of mice after trigeminal nerve injury and in lumbar spinal dorsal
      horn neurons of mice after SNL. We provide multiple lines of evidence that MrgC
      agonism at spinal but not peripheral sites may constitute a novel pain inhibitory
      mechanism that involves inhibition of peripheral excitatory inputs onto
      postsynaptic dorsal horn neurons in different rodent models of neuropathic pain. 

PMID- 24333782
TI  - Acute Absorb bioresorbable vascular scaffold thrombosis in ST-segment elevation
      myocardial infarction: to stent or not to stent?

PMID- 24333781
TI  - Prostacyclin mediates neuropathic pain through interleukin 1beta-expressing
      resident macrophages.
AB  - Prostacyclin is an important mediator of peripheral pain sensation. Here, we
      investigated its potential participation in mediating neuropathic pain and found
      that prostacyclin receptor (IP) knockout mice exhibited markedly decreased pain
      behavior. Application of an IP antagonist to the injury site or selective IP
      deficiency in myeloid cells mimicked the antinociceptive effect observed in IP
      knockout mice. At the site of nerve injury, IP was expressed in interleukin (IL)
      1beta-containing resident macrophages, which were less common in IP knockout
      mice. Local administration of the IP agonist cicaprost inhibited macrophage
      migration in vitro and promoted accumulation of IP- and IL1beta-expressing cells
      as well as an increase of IL1beta concentrations at the application site in vivo.
      Fittingly, the IL1-receptor antagonist anakinra (IL-1ra) decreased neuropathic
      pain behavior in wild-type mice but not in IP knockout mice. Finally, continuous,
      but not single administration, of the cyclooxygenase inhibitor meloxicam early
      after nerve injury decreased pain behavior and the number of resident
      macrophages. Thus, early synthesis of prostacyclin at the site of injury causes
      accumulation of IL1beta-expressing macrophages as a key step in neuropathic pain
      after traumatic injury. 

PMID- 24333783
TI  - Retinal proteins as model systems for membrane protein folding.
AB  - Experimental folding studies of membrane proteins are more challenging than water
      soluble proteins because of the higher hydrophobicity content of membrane
      embedded sequences and the need to provide a hydrophobic milieu for the
      transmembrane regions. The first challenge is their denaturation: due to the
      thermodynamic instability of polar groups in the membrane, secondary structures
      in membrane proteins are more difficult to disrupt than in soluble proteins. The
      second challenge is to refold from the denatured states. Successful refolding of
      membrane proteins has almost always been from very subtly denatured states.
      Therefore, it can be useful to analyze membrane protein folding using
      computational methods, and we will provide results obtained with simulated
      unfolding of membrane protein structures using the Floppy Inclusions and Rigid
      Substructure Topography (FIRST) method. Computational methods have the advantage
      that they allow a direct comparison between diverse membrane proteins. We will
      review here both, experimental and FIRST studies of the retinal binding proteins
      bacteriorhodopsin and mammalian rhodopsin, and discuss the extension of the
      findings to deriving hypotheses on the mechanisms of folding of membrane proteins
      in general. This article is part of a Special Issue entitled: Retinal Proteins
      You can teach an old dog new tricks. 

PMID- 24333784
TI  - Recent advances in understanding the molecular mechanism of chloroplast
      photorelocation movement.
AB  - Plants are photosynthetic organisms that have evolved unique systems to adapt
      fluctuating environmental light conditions. In addition to well-known movement
      responses such as phototropism, stomatal opening, and nastic leaf movements,
      chloroplast photorelocation movement is one of the essential cellular responses
      to optimize photosynthetic ability and avoid photodamage. For these adaptations,
      chloroplasts accumulate at the areas of cells illuminated with low light (called
      accumulation response), while they scatter from the area illuminated with strong
      light (called avoidance response). Plant-specific photoreceptors (phototropin,
      phytochrome, and/or neochrome) mediate these dynamic directional movements in
      response to incident light position and intensity. Several factors involved in
      the mechanisms underlying the processes from light perception to actin-based
      movements have also been identified through molecular genetic approach. This
      review aims to discuss recent findings in the field relating to how chloroplasts
      move at molecular levels. This article is part of a Special Issue entitled:
      Dynamic and ultrastructure of bioenergetic membranes and their components. 

PMID- 24333785
TI  - Repressible chloroplast gene expression in Chlamydomonas: a new tool for the
      study of the photosynthetic apparatus.
AB  - A repressible/inducible chloroplast gene expression system has been used to
      conditionally inhibit chloroplast protein synthesis in the unicellular alga
      Chlamydomonas reinhardtii. This system allows one to follow the fate of
      photosystem II and photosystem I and their antennae upon cessation of chloroplast
      translation. The main results are that the levels of the PSI core proteins
      decrease at a slower rate than those of PSII. Amongst the light-harvesting
      complexes, the decrease of CP26 proceeds at the same rate as for the PSII core
      proteins whereas it is significantly slower for CP29, and for the antenna
      complexes of PSI this rate is comprised between that of CP26 and CP29. In marked
      contrast, the components of trimeric LHCII, the major PSII antenna, persist for
      several days upon inhibition of chloroplast translation. This system offers new
      possibilities for investigating the biosynthesis and turnover of individual
      photosynthetic complexes in the thylakoid membranes. This article is part of a
      special issue entitled: photosynthesis research for sustainability: keys to
      produce clean energy.

PMID- 24333786
TI  - Bioenergetics and anaerobic respiratory chains of aceticlastic methanogens.
AB  - Methane-forming archaea are strictly anaerobic microbes and are essential for
      global carbon fluxes since they perform the terminal step in breakdown of organic
      matter in the absence of oxygen. Major part of methane produced in nature derives
      from the methyl group of acetate. Only members of the genera Methanosarcina and
      Methanosaeta are able to use this substrate for methane formation and growth.
      Since the free energy change coupled to methanogenesis from acetate is only 
      36kJ/mol CH4, aceticlastic methanogens developed efficient energy-conserving
      systems to handle this thermodynamic limitation. The membrane bound electron
      transport system of aceticlastic methanogens is a complex branched respiratory
      chain that can accept electrons from hydrogen, reduced coenzyme F420 or reduced
      ferredoxin. The terminal electron acceptor of this anaerobic respiration is a
      mixed disulfide composed of coenzyme M and coenzyme B. Reduced ferredoxin has an
      important function under aceticlastic growth conditions and novel and well
      established membrane complexes oxidizing ferredoxin will be discussed in depth.
      Membrane bound electron transport is connected to energy conservation by proton
      or sodium ion translocating enzymes (F420H2 dehydrogenase, Rnf complex, Ech
      hydrogenase, methanophenazine-reducing hydrogenase and heterodisulfide
      reductase). The resulting electrochemical ion gradient constitutes the driving
      force for adenosine triphosphate synthesis. Methanogenesis, electron transport,
      and the structure of key enzymes are discussed in this review leading to a
      concept of how aceticlastic methanogens make a living. This article is part of a
      Special Issue entitled: 18th European Bioenergetic Conference. 

PMID- 24333787
TI  - [Results and objectives of the fight against AIDS, tuberculosis and malaria
      debate organized by the Monde diplomatique and the Global Fund Paris, June 6th
      2013].

PMID- 24333788
TI  - Chemical biology approaches for the study of apicomplexan parasites.
AB  - Chemical biology and the techniques the field encompasses provide scientists with
      the means to address biological questions in ever-evolving and technically
      sophisticated ways. They facilitate the dissection of molecular mechanisms of
      cell phenomena on timescales not achievable by other means. Libraries of small
      molecules, bioorthogonal chemistries and technical advances in mass-spectrometry
      techniques enable the modern chemical biologist to tackle even the most difficult
      of biological questions. It is because of their broad applicability that these
      approaches are well suited to systems less tractable to more classical genetic
      methods. As such, the parasite community has embraced them with great success.
      Some of these successes and the continuing evolution of chemical biology applied
      to apicomplexans will be discussed. 

PMID- 24333789
TI  - Acaricidal activity of essential oil from Lippia sidoides on unengorged larvae
      and nymphs of Rhipicephalus sanguineus (Acari: Ixodidae) and Amblyomma cajennense
      (Acari: Ixodidae).
AB  - The aims of this work were to identify the compounds and to investigate the
      acaricidal activity of the essential oil of Lippia sidoides for unengorged larvae
      and nymphs of Rhipicephalus sanguineus and Amblyomma cajennense. The oil was
      analyzed by gas chromatography and gas chromatography/mass spectrometry. In
      total, 22 compounds comprising 98.5% of the total peak area were identified. The
      major constituent of the essential oil was thymol (69.9%). The acaricidal
      activity against larvae and nymphs was assessed using a modified larval packet
      test. In all experiments, oils were tested at concentrations of 2.35, 4.70, 9.40
      14.10 and 18.80 mg/mL. The mortalities of larvae and nymphs of R. sanguineus were
      20.6, 47.8, 73.6, 99.5 and 99.0% and 12.0, 50.0, 76.3, 96.0 and 96.1%,
      respectively. For larvae and nymphs of A. cajennense the rates of mortality were
      41.9, 63.3, 77.8, 82.5 and 100.0% and 0.0, 32.8, 64.8, 71.1 and 94.0%,
      respectively. The LC 90 values of the L. sidoides oil were 11.56 and 12.97 mg/mL
      for larvae and nymphs of R. sanguineus and 15.70 and 18.52 mg/mL for larvae and
      nymphs of A. cajennense, respectively. The essential oil from L. sidoides has
      acaricidal activity on unengorged larvae and nymphs of R. sanguineus and A.
      cajennense.

PMID- 24333790
TI  - A family of serine protease inhibitors (serpins) in the cattle tick Rhipicephalus
      (Boophilus) microplus.
AB  - Proteins belonging to the serine protease inhibitor (serpin) superfamily play
      essential roles in many organisms. In arthropods these proteins are involved in
      innate immune system, morphogenesis and development. In mammals serpins regulate
      pathways that are essential to life such as blood coagulation, fibrinolysis,
      inflammation and complement activation, some of which are considered the host's
      first line of defense to hematophagous and/or blood dueling parasites. Thus, it
      is hypothesized that ticks use serpins to evade host defense, facilitating
      parasitism. This study describes eighteen full-length cDNA sequences encoding
      serpins identified in Rhipicephalus (Boophilus) microplus, here named RmS 1-18
      (R. microplus serpin). Spatial and temporal transcriptional profiling
      demonstrated that R. microplus serpins are transcribed during feeding, suggesting
      their participation in tick physiology regulation. We speculate that the majority
      of R. microplus serpins are conserved in other ticks, as indicated by phylogeny
      analysis. Over half of the 18 RmSs are putatively functional in the extracellular
      environment, as indicated by putative signal peptides on 11 of 18 serpins.
      Comparative modeling and structural-based alignment revealed that R. microplus
      serpins in this study retain the consensus secondary of typical serpins. This
      descriptive study enlarges the knowledge on the molecular biology of R.
      microplus, an important tick species. 

PMID- 24333791
TI  - Cognitive decline, dietary factors and gut-brain interactions.
AB  - Cognitive decline in elderly people often derives from the interaction between
      aging-related changes and age-related diseases and covers a large spectrum of
      clinical manifestations, from intact cognition through mild cognitive impairment
      and dementia. Epidemiological evidence supports the hypothesis that modifiable
      lifestyle-related factors are associated with cognitive decline, opening new
      avenues for prevention. Diet in particular has become the object of intense
      research in relation to cognitive aging and neurodegenerative disease. We
      reviewed the most recent findings in this rapidly expanding field. Some
      nutrients, such as vitamins and fatty acids, have been studied longer than
      others, but strong scientific evidence of an association is lacking even for
      these compounds. Specific dietary patterns, like the Mediterranean diet, may be
      more beneficial than a high consumption of single nutrients or specific food
      items. A strong link between vascular risk factors and dementia has been shown,
      and the association of diet with several vascular and metabolic diseases is well
      known. Other plausible mechanisms underlying the relationship between diet and
      cognitive decline, such as inflammation and oxidative stress, have been
      established. In addition to the traditional etiological pathways, new hypotheses,
      such as the role of the intestinal microbiome in cognitive function, have been
      suggested and warrant further investigation. 

PMID- 24333792
TI  - Syntrophic acetate oxidation in industrial CSTR biogas digesters.
AB  - The extent of syntrophic acetate oxidation (SAO) and the levels of known SAO
      bacteria and acetate- and hydrogen-consuming methanogens were determined in
      sludge from 13 commercial biogas production plants. Results from these
      measurements were statistically related to the prevailing operating conditions,
      through partial least squares (PLS) analysis. This revealed that high abundance
      of microorganisms involved in SAO was positively correlated with relatively low
      abundance of aceticlastic methanogens and high concentrations of free ammonia
      (>160 mg/L) and volatile fatty acids (VFA). Temperature was identified as another
      influencing factor for the population structure of the syntrophic acetate
      oxidising bacteria (SAOB). Overall, there was a high abundance of SAOB in the
      different digesters despite differences in their operating parameters, indicating
      that SAOB are an enduring and important component of biogas-producing consortia.

PMID- 24333794
TI  - Daucosterol promotes the proliferation of neural stem cells.
AB  - Neural stem cells (NSCs) are self-regenerating cells, but their regenerative
      capacity is limited. The present study was conducted to investigate the effect of
      daucosterol (a sterolin) on the promotion of NSC proliferation and determine the
      corresponding molecular mechanism. Results of cell counting kit-8 (CCK-8) assay
      showed that daucosterol significantly increased the quantity of viable cells and
      the effectiveness of daucosterol was similar to that of basic fibroblast growth
      factor (bFGF) and epidermal growth factor (EGF). Flow cytometry detection of CFSE
      labeled (CFSE, carboxyfluorescein diacetate succinimidyl ester) NSCs showed that
      Div Index (or the average number of cell divisions) and % Divided (or the
      percentage of cells that divided at least once) of the cells were increased,
      indicating that daucosterol increased the percentage of NSCs re-entering the cell
      cycle. mRNA microarray analysis showed that 333 genes that are mostly involved in
      the mitotic cell cycle were up-regulated. By contrast, 627 genes that are mostly
      involved in differentiation were down-regulated. In particular, insulin-like
      growth factor I (IGF1) was considered as an important regulatory gene that
      functionally promoted NSC proliferation, and the increased expression of IGF1
      protein was validated by ELISA. In addition, the phosphorylation of AKT was
      increased, indicating that the proliferation-enhancing activity of daucosterol
      may be involved in IGF1-AKT pathway. Our study provided information about
      daucosterol as an efficient and inexpensive growth factor alternative that could
      be used in clinical medicine and research applications. 

PMID- 24333793
TI  - Post-translational modifications of the progesterone receptors.
AB  - Progesterone plays a key role in the development, differentiation and maintenance
      of female reproductive tissues and has multiple non-reproductive neural
      functions. Depending on the cell and tissue, the hormonal environment, growth
      conditions and the developmental stage, progesterone can either stimulate cell
      growth or inhibit it while promoting differentiation. Progesterone receptors
      (PRs) belong to the steroid hormone receptor superfamily of ligand-dependent
      transcription factors. PR proteins are subject to extensive post-translational
      modifications that include phosphorylation, acetylation, ubiquitination and
      SUMOylation. The interplay among these modifications is complex with alteration
      of the receptors by one factor influencing the impact of another. Control over
      these modifications is species-, tissue- and cell-specific. They in turn regulate
      multiple functions including PR stability, their subcellular localization,
      protein-protein interactions and transcriptional activity. These complexities may
      explain how tissue- and gene-specific differences in regulation are achieved in
      the same organism, by the same receptor protein and hormone. Here we review
      current knowledge of PR post-translational modifications and discuss how these
      may influence receptor function focusing on human breast cancer cells. There is
      much left to be learned. However, our understanding of this may help to identify
      therapeutic agents that target PR activity in tissue-specific, even gene-specific
      ways. 

PMID- 24333795
TI  - The longitudinal association of vitamin D serum concentrations & adiposity
      phenotype.
AB  - Several cross-sectional studies have reported on the association between serum 25
      hydroxy vitamin D concentrations (25(OH)D) and body mass index (BMI). We examined
      the longitudinal effect of BMI on serum 25(OH)D concentrations among 866 Puerto
      Rican adults living in the Greater Boston area: 246 men and 620 women, aged 45-75
      years at baseline and 2 year. Our analyses showed negative correlations at two
      time points between BMI and serum 25(OH)D concentrations. The multivariate
      analysis showed that when predicting the change of serum 25(OH)D concentrations,
      baseline-BMI had significant inverse association (P<0.04) controlling for age,
      sex, and baseline-BMI. This association remained significant after adjusting for
      vitamin D supplement use, smoking, miles walked/day and alcohol intake (P<0.01).
      In conclusion, the major findings of the present study are obesity (1) was
      inversely associated with 25(OH)D at baseline; (2) with the change in serum
      25(OH)D at 2-year in this population of older Puerto Rican adults living in the
      Boston area. This article is part of a Special Issue entitled '16th Vitamin D
      Workshop'. 

PMID- 24333796
TI  - Reference ranges for urinary levels of testosterone and epitestosterone, which
      may reveal gonadal function, in a Korean male population.
AB  - Cannabis, or marijuana, the most commonly used illicit drug in the world, has
      been shown to be responsible for suppressing the production and secretion of
      androgens, particularly testosterone. However, despite such findings in animals,
      the chronic effects of marijuana use on human endocrine systems have proved to be
      inconsistent. Here, we investigated the reference ranges of urinary levels of
      testosterone (T) and epitestosterone (E) as well as their metabolic ratio of T/E
      in a Korean male population (n=337), which would enable an evaluation of abnormal
      changes in steroid metabolism induced by habitually administered cannabis. The
      T/E ratio was significantly decreased in the marijuana group (n=18), while the
      urinary testosterone concentrations were also tended to decrease. This study is
      the first to provide data for the reference values of two urinary androgens and
      T/E values among control Korean males, and, furthermore, suggests that the T/E
      ratio, though not testosterone levels, might be used to understand the
      suppression of human male gonadal function affected by smoking marijuana. 

PMID- 24333797
TI  - Comparison of natural estrogens and synthetic derivative on genioglossus function
      and estrogen receptors expression in rats with chronic intermittent hypoxia.
AB  - The pathogenesis of obstructive sleep apnea--hypopnea syndrome (OSAHS) is
      summarized as the narrow anatomic structure of upper airway (UA) and the
      defective function of UA dilator muscles. Up to now, there have been no specific
      treatments for the UA dilator muscle deficiency. We previously found that some
      estrogen-like compounds exert protective effects on genioglossus, but this
      protection tends to be less satisfactory. A novel phytoestrogen derivative was
      synthesized in recent years and was verified to have some cytoprotective
      activity. This study was designed to compare the effects of natural estrogens and
      the synthetic resveratrol dimer on genioglossus contraction and expression of
      estrogen receptors (ERs) under chronic intermittent hypoxia (CIH) condition.
      Genioglossus myoblasts of rat were isolated and cultured in a culture medium with
      different agents (estradiol, genistein, resveratrol, and resveratrol dimer,
      respectively) under hypoxia condition, and ERs expressions were detected. In vivo
      study, 48 ovariectomized female rats were randomized into six groups. After CIH
      exposure and agents injection, rats were tested for genioglossus contractile
      properties and further analysis of ERs expression. Estradiol up-regulated ERalpha
      level and exerted the best protective effect of fatigue resistance. Genistein,
      resveratrol and resveratrol dimer primarily up-regulated the expression of
      ERbeta. Resveratrol dimer exhibited better protection of fatigue resistance than
      genistein and resveratrol, and expressed higher binding affinity for ERbeta than
      for ERalpha. Besides estrogenic effects, there may be some other mechanisms for
      the fatigue resistance improvement contributed by phytoestrogens and their
      derivatives.

PMID- 24333798
TI  - Predictors of serum 25(Oh)D increase following bimonthly supplementation with
      100,000IU vitamin D in healthy, men aged 25-65 years.
AB  - Vitamin D replenishment therapy typically entails standard dosages, but related
      increases in serum 25(OH)D levels vary between individuals. This study was aimed
      to identify factors that affect the efficacy of vitamin D supplementation.
      SUBJECTS AND METHODS: 79 healthy men aged 25-65 with 25(OH)D<20ng/ml participated
      in a vitamin D supplementation study. All participants received 100,000IU vitamin
      D bimonthly, e.g., 1666IU/day. Personal and demographic information, physical
      activity and sun-exposure questionnaires were completed by the participants.
      Weight, height, and waist circumference were recorded. Serum calcium, creatinine,
      25(OH)D, PTH, lipid profile, and liver-enzyme levels were assessed. All
      measurements were repeated after 6 and 12 months. The difference between baseline
      serum 25(OH)D and 12-month measurements was calculated (delta). Linear regression
      was performed to identify predictors for increases in 25(OH)D levels. RESULTS:
      Mean serum 25(OH)D level increases according to BMI were 12.6+/-5.29ng/ml for
      BMI<=25, 10.12+/-4.95ng/ml for 25<BMI<30, and only 6.39+/- 5.33ng/ml for BMI>30,
      which differed significantly from the other BMI categories (p=0.003). In a
      regression model to predict 25(OH)D increase, BMI was the main predictor
      (p<0.001), explaining 21.6% of the variance in serum 25(OH)D (inverse
      association). Age, sun-exposure, serum cholesterol, physical-activity, baseline
      25(OH)D levels and seasonality were insignificant. The full model explained 27.9%
      of the variance in serum 25(OH)D. CONCLUSION: This study's main findings are that
      BMI affect vitamin D response in healthy men. Quantitative supplementation
      adjustments may be warranted in obese men, for whom the dose may need to be
      doubled. This article is part of a special issue entitled '16th Vitamin D
      Workshop'.

PMID- 24333799
TI  - The "newer" progestogens and postmenopausal hormone therapy (HRT).
AB  - After a worldwide breakdown of hormone therapy [HT] following the publications of
      the Women's Health Initiative trial and Million Women's Study in 2002-2003, there
      is now a trend to turn attention again to HT and to explore particular
      progestogens, which have been discredited with respect to their side effects. The
      progestogens to be considered should control undue proliferation of the
      endometrium and should not interfere negatively with the positive effects of
      estradiol, regarding carbohydrate and lipid metabolism as well as hemostasis. In
      the present review, three "newer progestogens" are scrutinized regarding their
      various actions, in combination with estradiol; the progestogens include
      dienogest, drospirenone and nomegestrol acetate. This article is part of a
      special issue entitled Menopause. 

PMID- 24333800
TI  - Solid-state NMR spectroscopy to study protein-lipid interactions.
AB  - The appropriate lipid environment is crucial for the proper function of membrane
      proteins. There is a tremendous variety of lipid molecules in the membrane and so
      far it is often unclear which component of the lipid matrix is essential for the
      function of a respective protein. Lipid molecules and proteins mutually influence
      each other; parameters such as acyl chain order, membrane thickness, membrane
      elasticity, permeability, lipid-domain and annulus formation are strongly
      modulated by proteins. More recent data also indicates that the influence of
      proteins goes beyond a single annulus of next-neighbor boundary lipids.
      Therefore, a mesoscopic approach to membrane lipid-protein interactions in terms
      of elastic membrane deformations has been developed. Solid-state NMR has greatly
      contributed to the understanding of lipid-protein interactions and the modern
      view of biological membranes. Methods that detect the influence of proteins on
      the membrane as well as direct lipid-protein interactions have been developed and
      are reviewed here. Examples for solid-state NMR studies on the interaction of Ras
      proteins, the antimicrobial peptide protegrin-1, the G protein-coupled receptor
      rhodopsin, and the K(+) channel KcsA are discussed. This article is part of a
      Special Issue entitled Tools to study lipid functions. 

PMID- 24333802
TI  - The effect of telecare on the quality of life and psychological well-being of
      elderly recipients of social care over a 12-month period: the Whole Systems
      Demonstrator cluster randomised trial.
AB  - BACKGROUND: home-based telecare (TC) is utilised to manage risks of independent
      living and provide prompt emergency responses. This study examined the effect of
      TC on health-related quality of life (HRQoL), anxiety and depressive symptoms
      over 12 months in patients receiving social care. DESIGN: a study of participant
      reported outcomes [the Whole Systems Demonstrator (WSD) Telecare Questionnaire
      Study; baseline n = 1,189] was nested in a pragmatic cluster-randomised trial of
      TC (the WSD Telecare trial), held across three English Local Authorities. General
      practice (GP) was the unit of randomisation and TC was compared with usual care
      (UC). METHODS: participant-reported outcome measures were collected at baseline,
      short-term (4 months) and long-term (12 months) follow-up, assessing generic
      HRQoL, anxiety and depressive symptoms. Primary intention-to-treat analyses
      tested treatment effectiveness and were conducted using multilevel models to
      control for GP clustering and covariates for participants who completed
      questionnaire measures at baseline assessment plus at least one other assessment
      (n = 873). RESULTS: analyses found significant differences between TC and UC on
      Short Form-12 mental component scores (P < 0.05), with parameter estimates
      indicating being a member of the TC trial-arm increases mental component scores
      (UC-adjusted mean = 40.52; TC-adjusted mean = 43.69). Additional significant
      analyses revealed, time effects on EQ5D (decreasing over time) and depressive
      symptoms (increasing over time). CONCLUSIONS: TC potentially contributes to the
      amelioration in the decline in users' mental HRQoL over a 12-month period. TC may
      not transform the lives of its users, but it may afford small relative benefits
      on some psychological and HRQOL outcomes relative to users who only receive UC.
      International Standard Randomised Controlled Trial Number Register: ISRCTN
      43002091.

PMID- 24333803
TI  - BODE index or geriatric multidimensional assessment for the prediction of very
      long-term mortality in elderly patients with chronic obstructive pulmonary
      disease? a prospective cohort study.
AB  - BACKGROUND: a multidimensional approach-the BODE index-has been proposed for
      prognostic purposes in chronic obstructive pulmonary disease (COPD) and
      theoretically seems to be well suited for elderly people, but there is a lack of
      data in this population, especially with respect to long-term survival. The
      objective of this study is to evaluate whether the BODE index can predict both
      long (5 years) and very-long (10 and 15 years)-term mortality in an unselected
      population of elderly people with COPD better than a set of variables commonly
      taken into account in a geriatric multidimensional assessment (MDA). METHODS: :
      this was a multicentre, prospective, population study. We used data from the SaRA
      study, which included 563 elderly people with COPD whose vital status was
      ascertained for up to 15 years after enrolment. The discriminative capacity of
      the BODE index in predicting mortality was derived from Cox proportional hazard
      models including the components of the BODE index and compared with that of an
      alternative model based on MDA variables: age, gender, physical disability,
      cognitive function and mood status. RESULTS: : at 5 years, the HRs for mortality
      were 1.04 (95% CI: 0.60-1.79), 1.88 (1.10-3.22) and 3.55 (2.15-5.86) for
      quartiles 2-4, respectively, compared with quartile 1 of the BODE index. The
      corresponding figures for 10-year mortality were 1.50 (1.01-2.24), 2.11 (1.39
      3.20) and 3.903 (2.62-5.82), and for 15-year mortality were 1.68 (1.19-2.36),
      2.08 (1.44-3.01) and 3.78 (2.64-5.41). Similar results were obtained using
      variables included in the usual MDA. CONCLUSIONS: : Both the 'classic' MDA and
      the BODE index are comparably associated with mortality, even at very long term,
      in elderly people with COPD.

PMID- 24333801
TI  - Dystonia as a network disorder: what is the role of the cerebellum?
AB  - The dystonias are a group of disorders defined by sustained or intermittent
      muscle contractions that result in involuntary posturing or repetitive movements.
      There are many different clinical manifestations and causes. Although they
      traditionally have been ascribed to dysfunction of the basal ganglia, recent
      evidence has suggested dysfunction may originate from other regions, particularly
      the cerebellum. This recent evidence has led to an emerging view that dystonia is
      a network disorder that involves multiple brain regions. The new network model
      for the pathogenesis of dystonia has raised many questions, particularly
      regarding the role of the cerebellum. For example, if dystonia may arise from
      cerebellar dysfunction, then why are there no cerebellar signs in dystonia? Why
      are focal cerebellar lesions or degenerative cerebellar disorders more commonly
      associated with ataxia rather than dystonia? Why is dystonia more commonly
      associated with basal ganglia lesions rather than cerebellar lesions? Can answers
      obtained from animals be extrapolated to humans? Is there any evidence that the
      cerebellum is not involved? Finally, what is the practical value of this new
      model of pathogenesis for the neuroscientist and clinician? This article explores
      potential answers to these questions. 

PMID- 24333804
TI  - Visual-perceptual-kinesthetic inputs on influencing writing performances in
      children with handwriting difficulties.
AB  - This study investigated the role of visual-perceptual input in writing Chinese
      characters among senior school-aged children who had handwriting difficulties
      (CHD). The participants were 27 CHD (9-11 years old) and 61 normally developed
      control. There were three writing conditions: copying, and dictations with or
      without visual feedback. The motor-free subtests of the Developmental Test of
      Visual Perception (DTVP-2) were conducted. The CHD group showed significantly
      slower mean speeds of character production and less legibility of produced
      characters than the control group in all writing conditions (ps<0.001). There
      were significant deteriorations in legibility from copying to dictation without
      visual feedback. Nevertheless, the Group by Condition interaction effect was not
      statistically significant. Only position in space of DTVP-2 was significantly
      correlated with the legibility among CHD (r=-0.62, p=0.001). Poor legibility
      seems to be related to the less-intact spatial representation of the characters
      in working memory, which can be rectified by viewing the characters during
      writing. Visual feedback regarding one's own actions in writing can also improve
      legibility of characters among these children. 

PMID- 24333805
TI  - Emergence and stability of interlimb coordination patterns in children with
      developmental coordination disorder.
AB  - The purpose of this study was to investigate the emergence and stability of
      coordination patterns in children with developmental coordination disorder (DCD)
      when performing a rhythmic interlimb coordination task on rigid (floor) and
      elastic (mini-trampoline) surfaces. Twelve typically developing (TD) children and
      12 children with DCD were required to clap while jumping under different
      conditions: in a chosen pattern - Free; when the feet touched the surface -
      Clapping-surface; when the body reached the maximum jumping height - Clapping
      jump; and when the feet touched the surface and the body reached the maximum
      jumping height - Clapping-both. The results showed that the coordination pattern
      of children with DCD was more variable in the Free, Clapping-surface, and
      Clapping-jumping conditions and more variable on the mini-trampoline than on the
      floor under the Free condition when compared with the TD children. Clapping
      jumping was more difficult to perform than Clapping-surface for both groups.
      These findings suggest that the children with DCD were less capable of
      rhythmically coordinating the jumping-clapping task because they used a type of
      exploratory strategy regarding the physical properties of the surfaces, whereas
      the TD children used a type of adaptive strategy displaying behavior that was
      more consistent across the tasks/environmental demands. 

PMID- 24333806
TI  - A longitudinal study on gross motor development in children with learning
      disorders.
AB  - This longitudinal study examined the development of gross motor skills, and sex
      differences therein, in 7- to 11-years-old children with learning disorders (LD)
      and compared the results with typically developing children to determine the
      performance level of children with LD. In children with LD (n=56; 39 boys, 17
      girls), gross motor skills were assessed with the Test of Gross Motor Development
      2 and measured annually during a 3-year period. Motor scores of 253 typically
      developing children (125 boys, 112 girls) were collected for references values.
      The multilevel analyses showed that the ball skills of children with LD improved
      with age (p<.001), especially between 7 and 9 years, but the locomotor skills did
      not (p=.50). Boys had higher ball skill scores than girls (p=.002) and these
      differences were constant over time. Typically developing children outperformed
      the children with LD on the locomotor skills and ball skills at all ages, except
      the locomotor skills at age 7. Children with LD develop their ball skills later
      in the primary school-period compared to typically developing peers. However, 11
      year-old children with LD had a lag in locomotor skills and ball skills of at
      least four and three years, respectively, compared to their peers. 

PMID- 24333807
TI  - Trends in the use of psychotropic drugs in people with intellectual disability in
      Taiwan: a nationwide outpatient service study, 1997-2007.
AB  - This study aims to examine trends in outpatient psychotropic drug use among
      people with intellectual disabilities in Taiwan. The NHI outpatient medication
      records between January 1, 1997 and December 31, 2007 for people with
      intellectual disabilities were analyzed to observe the percent change, prevalence
      and prescription trends in psychotropic drugs. The overall prevalence of
      psychotropic medication increased from 17.82% to 23.22% during the study period.
      Results from stepwise logistic analysis demonstrated that females, the elderly,
      and individuals suffering from catastrophic disease were more prone to receive
      psychotropic drugs and that those with mild intellectual disability were less
      likely to receive psychotropic drugs. The percentage change in prescription rates
      of antipsychotics, hypnotics/sedatives, and antidepressants were 85.30%, 127.25%,
      and 167.50%, respectively, and the trends were statistically significant
      (p<0.05). Taiwan's NHI program and off-label use of psychotropic drugs might have
      attributed to this trend. 

PMID- 24333808
TI  - The effect of additional noradrenergic and serotonergic depletion on a
      lateralised choice reaction time task in rats with nigral 6-OHDA lesions.
AB  - Parkinson's disease (PD) patients often suffer from visuospatial deficits, which
      have been considered a disruption of the representation of external space. The
      lateralised choice reaction time (CRT) task is an operant task for rodents in
      which similar deficits can be assessed. It has been demonstrated that specific
      parameters in this task is disrupted after unilateral injections of 6
      hydroxydopamine (6-OHDA), which have been associated with the dopamine (DA)
      depletion that inevitably follows this type of lesion. However, studies have
      demonstrated that this type of lesion also affects the serotonergic (5HT) and
      noradrenergic (NA) systems. However, the impact of these systems on parameters in
      the CRT task had not yet been investigated. To this end, rats were pretrained on
      the CRT task before receiving selective lesions of the DAergic system, either
      alone or in combination with depletion of the NA or 5HT system. All rats with a 6
      OHDA lesion displayed a gradual decline in the selection, initiation and
      execution of lateralised movements compared to sham-lesion controls on the side
      contralateral to the lesion. They also displayed a reduced number of useable
      trials as well as an increased number of procedural errors. Interestingly, the
      group with an additional noradrenergic lesion was significantly slower in
      reacting to lateralised stimuli throughout the testing period compared to the
      other two groups with a 6-OHDA lesion. There was however no difference between
      the three different lesion groups in the other parameters assessed in the task.
      These data confirm previous findings demonstrating that the majority of the
      parameters assessed in the lateralised CRT task are strongly dependent on DA.
      However, this study has also shown that the NAergic system may play an important
      role in contributing to the attentive performance influencing the capacity to
      react to the presented lateralised stimuli. 

PMID- 24333809
TI  - Mental rotation and the motor system: embodiment head over heels.
AB  - We examined whether body parts attached to abstract stimuli automatically force
      embodiment in a mental rotation task. In Experiment 1, standard cube combinations
      reflecting a human pose were added with (1) body parts on anatomically possible
      locations, (2) body parts on anatomically impossible locations, (3) colored end
      cubes, and (4) simple end cubes. Participants (N=30) had to decide whether two
      simultaneously presented stimuli, rotated in the picture plane, were identical or
      not. They were fastest and made less errors in the possible-body condition, but
      were slowest and least accurate in the impossible-body condition. A second
      experiment (N=32) replicated the results and ruled out that the poor performance
      in the impossible-body condition was due to the specific stimulus material. The
      findings of both experiments suggest that body parts automatically trigger
      embodiment, even when it is counterproductive and dramatically impairs
      performance, as in the impossible-body condition. It can furthermore be concluded
      that body parts cannot be used flexibly for spatial orientation in mental
      rotation tasks, compared to colored end cubes. Thus, embodiment appears to be a
      strong and inflexible mechanism that may, under certain conditions, even impede
      performance. 

PMID- 24333810
TI  - More conflict does not trigger more adjustment of cognitive control for
      subsequent events: a study of the bivalency effect.
AB  - Encountering a conflict triggers an adjustment of cognitive control. This
      adjustment of cognitive control can even affect subsequent performance. The
      purpose of the present study was to determine whether more conflict triggers more
      adjustment of cognitive control for subsequent performance. To this end, we
      focussed on the bivalency effect, that is, the adjustment of cognitive control
      following the conflict induced by bivalent stimuli (i.e., stimuli with relevant
      features for two tasks). In two experiments, we tested whether the amount of
      conflict triggered by bivalent stimuli affected the bivalency effect. Bivalent
      stimuli were either compatible (i.e., affording one response) or incompatible
      (i.e., affording two different responses). Thus, compatible bivalent stimuli
      involved a task conflict, whereas incompatible bivalent stimuli involved a task
      and a response conflict. The results showed that the bivalency effect was not
      affected by this manipulation. This indicates that more conflict does not trigger
      more adjustment of cognitive control for subsequent performance. Therefore, only
      the occurrence of conflict--not its amount--is determinant for cognitive control.

PMID- 24333811
TI  - [Bed-manager or health-care circuit manager].

PMID- 24333812
TI  - [Analysis of factors influencing self-rated health among older persons: synthesis
      of the biomedical literature].
AB  - Self-rated health is a frequently used measure, notably in the field of
      gerontology. Different authors have studied factors that can influence self-rated
      health among older persons and, according to studies, the factors taken into
      account and their influence vary. This article aims at synthesising the
      biomedical literature, published since 1993, on factors that influence self-rated
      health of non-institutionalised older persons aged 65 years and over, with a
      focus on cross-sectional quantitative studies. Of the 1801 articles that were
      identified by our search strategy in the Medline database, 22 were retained. The
      proportion of older persons assessing their health positively ranged, depending
      on the studies, from 48.4% to 78.0%. Fifteen studies out of 22 investigated what
      was rather associated with an unfavourable self-rated health. Two studies took
      into account only one kind of independent variables. In more than half of the
      studies, 1 to several variables belonging to at least 3 kinds of independent
      variables were associated with self-rated health in multivariable analysis. The
      associations between these different kinds of independent variables considered
      (sociodemographic characteristics - morbidity - functional status - mental health
      - social support - other variables) and self-rated health are here presented and
      synthesized. This work shows that the factors that influence self-rated health
      among older people, factors measured differently according to authors, are varied
      and belong to different domains. These domains include morbidity, functional
      status, as well as sociodemographic characteristics, mental health, certain
      aspects of social support and other kinds of factors. 

PMID- 24333813
TI  - [Quality of care provided to elderly fallers in the emergency room].
AB  - BACKGROUND: recurrent falls are a major public health problem associated with
      high morbidity and mortality as well as increased dependence. Multifactorial
      intervention has been shown to reduce recurrence by 20% (Profet study). The
      French Health Authority (Haute autorite de sante or HAS) recommends since 2009 a
      systematic screening for and assessment of risk factors as well as the
      implementation of preventive measures. OBJECTIVES: to examine whether the
      management of falls in older patients discharged home from the emergency
      department is consistent with the HAS guidelines. METHODS: descriptive
      retrospective analysis of 1238 medical records of patients over 75 years, who
      consulted for falls from April to October 2010 in the emergency department of in
      13 centers in the North-Alps region. The study is part of a program to improve
      the quality of care led by the French Network of North-Alps Emergency Departments
      (Reseau nord alpin des urgences, RENAU). RESULTS: Screening of risk factors for
      falls was documented in varying rates: electrocardiogram 29%, cognitive
      impairment 25%, functional assessment 16%, walking difficulties 11%, postural
      hypotension 5%. A comprehensive geriatric assessment was undertaken for 3.8% of
      the patients. CONCLUSION: risk factors for falls are insufficiently documented in
      elderly patients discharged home from the emergency room after a fall-related
      visit. Completeness rates are similar to those found in previous studies. A
      standardized protocol for older fallers, specifically adapted to the work routine
      in the emergency department could be useful. The RENAU has proposed an algorithm
      to streamline the orientation of older fallers and promote the use of geriatric
      network.

PMID- 24333814
TI  - [Corticotherapy withdrawal in older people].
AB  - Synthetic glucocorticoids treatment for their antiinflammatory and
      immunosuppressive activities for more than 3 weeks decreases corticotropic axis
      and induces a risk of adrenal insufficiency upon treatment withdrawal. Dose,
      duration and unknown individual factors play a role in the occurrence of adrenal
      insufficiency. Serum cortisol at 7-8 am, possibly completed by an 1-24 ACTH
      stimulation test makes the diagnosis. A scheme for care of patients is included
      with a progressive decrease of synthetic glucocorticoids dose, a replacement of
      this medication with physiological doses of hydrocortisone (in case of adrenal
      insufficiency) and a follow-up of endogenous secretion for detection of adrenal
      function recovery. 

PMID- 24333815
TI  - [Neurocognitive markers of suicide vulnerability in the elderly: a review].
AB  - OBJECTIVE: a comprehensive literature review suggests that suicidal behaviour
      results from a complex interplay between stressful events and vulnerability
      factors including cognitive deficits. The aim of this systematic literature
      review was to identify the neurocognitive markers associated with suicide
      vulnerability in elderly people. METHOD: a systematic English Medline literature
      search of cohort studies, case-control studies and cross-sectional studies
      published between January 1960 and December 2012 was performed, combining the
      MeSH terms "Suicide", "Neuropsychology", "Neuropsychological Tests", "Executive
      Function", "Magnetic Resonance Imaging", "Diffusion Magnetic Resonance Imaging",
      "Positron-Emission Tomography", "Prefrontal Cortex", "Tomography, Emission
      Computed, Single-Photon", and "Diffusion Tensor Imaging". The abstract selection
      was based on the Strobe checklist for observational studies. RESULTS: of the 446
      original articles, 10 neuropsychological and 4 brain imaging studies were
      selected. The number of suicidal subjects ranged from 10 to 29 (mean age=66.8 to
      79.1 years old, 0-85% women). Executive functions, in particular decision-making
      and cognitive inhibition, were more impaired in the depressed elderly with a
      history of suicide attempts compared to those without such a history. fMRI data,
      which need to be confirmed in further details, showed abnormalities of fronto
      limbic circuits which are involved in suicide vulnerability in the elderly
      independently of any associated psychopathological conditions including
      depression. CONCLUSION: this literature review confirms the existence of
      neurocognitive markers of suicide vulnerability in elderly people. A
      neuropsychological assessment could thus help to identify the suicide
      vulnerability of a depressed elderly person, a first step for both
      pharmacological and psychotherapeutic cares.

PMID- 24333816
TI  - [Neuromuscular system and aging: involutions and implications].
AB  - In aged human, the number of muscle fibers and motor units decreases. The
      remaining motor units lose their functionality (decrease of the discharge
      frequency, greater fluctuation of the discharge) particularly those which contain
      type II fibers. The renewal of intracellular proteins declines which creates a
      negative balance between the daily protein losses and the capacities to renew
      them. The activity of the protein kinase (Akt) that stimulates the synthesis of
      regulation proteins (mTOR, p70S6, IGFBP-5) declines whereas the factors of
      degradation of proteins (NF-kappa B) are activated. Besides, the process of
      activation and proliferation of satellite cells is affected and the production of
      anabolic hormones and local factors is decreased. After a strength training
      program, muscle hypertrophy is linked to the protein synthesis at the level of
      myosin heavy chain (MHC) isoforms in older subjects. However, the transcription
      of the genes that code the MHC-I (slow form) increases and the transcription of
      the genes that code the MHC-II (fast form) decreases. Thus, the transition of the
      phenotype towards a slower form cannot be inverted by strength training during
      the advanced in age. Moreover, strength training enables to decrease the
      proportion of fibers containing MHC of hybrid form in the process of evolution.
      Hence, strength training can engender a stabilization of the muscular phenotype
      i.e. different isoforms of MHC. In addition, strength training counteracts the
      noxious effects mentioned above by generating muscular hypertrophy thanks to a
      reactive increase in the production of anabolic hormones. A program of aerobic
      training can induce an increase in the synthesis of ARN messengers coding
      isoforms related to the oxidative metabolism (MHC-I and to a lesser extent MHC
      IIa) while the transcribed for the type MHC-IIx decrease. 

PMID- 24333818
TI  - [Publication of DSM-V].

PMID- 24333817
TI  - [Comprehensive geriatric assessment in intensive care unit: a pilot study (pre
      Seniorea)].
AB  - BACKGROUND: long-term outcomes of elderly patients after an intensive care unit
      (ICU) stay are not fully elucidated. The objective of the pre-Seniorea study was
      to examine the feasibility of comprehensive geriatric assessment (CGA) during and
      after the ICU stay. METHODS: inpatients aged 75 years and over admitted to
      medical and surgical ICUs of Angers University Hospital, France, from june to
      september 2012, received a SGA (assessment of morbidities, frailty, cognition,
      anxiety, mood, nutrition, functional abilities, motor function, pain, caregiver
      burden and quality of life) at ICU admission (through a proxy interview), at the
      end of the ICU stay, and 3 month later in the place of life. RESULTS: fifty-two
      patients were included (81 [78; 83] years (median [25(th); 75(th) percentile]);
      35 males; SAPSII 47 [38; 56]; 80% ventilation). ICU survival was 73% (n=38), 58%
      (n=30) after three months, and 54% (n=28) after 12 months. The CGA at ICU
      admission was performed in all patients and lasted 10 [5; 10] minutes. The CGA at
      discharge was performed in all survivors and lasted 10 [5; 15] minutes. In all,
      26 survivors received CGA in their place of life after 3 months. Travel time by
      evaluators was 42 minutes, and time on site 45 [45; 60] minutes. At 3 months, 85%
      of surviving patients were at home and felt happy, 80% had preserved autonomy.
      The only variable predictive of survival at three months was the SAPSII score.
      CONCLUSION: the follow-up of elderly inpatient admitted to ICU with repeated
      CGAs, including long-term evaluations in the place of life, was feasible and well
      accepted. These results set the place for larger multicentric trials.

PMID- 24333819
TI  - [Systemic reading, another way of thinking to apprehend situations of elderly
      abuse].
AB  - In 2007, a national call number was created to receive reports of ill-treatment
      for aged or handicapped subjects, and departmental platforms of phone-tapping
      were organized. Professionals of listening receive the calls for assistance or
      confidences of distresses related to ill treatments. They should initiate a
      relationship and assess the danger of the condition, therefore, in a systemic
      paradigm, performing a double task. According to the systemic approach, ill
      treatments are usually the product of interaction and not that of an individual.
      They do not only concern individuals which suffer or undergo ill treatment but a
      system including all people leaving at home and social environment. To apprehend
      the complex relationships of ill treatments by professional of listening requires
      clarification of the situation together initiating a relation of confidence
      between the person calling and the professional. Therefore, the requests
      necessary for clarification should not be intrusive but create conditions of an
      exchange of information allowing a co-construction with the person calling for
      help. To accommodate a call for a critic situation, we need to take into account
      the context and not to be focused on the search of the causes of ill-treatment. 

PMID- 24333820
TI  - [Mental disorders due to brain lesions in the DSM-5 in the light of the previous
      versions].
AB  - The DSM-5 introduces major modifications in the category of mental disorders due
      to brain lesions compared to the previous DSM versions, which are reviewed in
      this paper. The description of the category Major neurocognitive disorder, as a
      substitute for dementia, seems to fit better for patients and families, and more
      adapted to many neurodegenerative cognitive disorders for which memory impairment
      is not predominant. Similarly, the introduction of the category of Mild
      neurocognitive disorder appears to be an improvement although some difficulty
      still remains for distinguishing mild cognitive disorder from normal aging. The
      addition of new etiological categories such as fronto-temporal NCD or NCD with
      Lewy bodies should also to be considered as a significant improvement. Despite
      these advances, to circumscribe the mental disorders due to brain lesions to
      cognitive deficits and biological mechanisms remains highly questionable, and
      does not provide an adequate care for the patients and families if not
      complemented by a psychological and environmental approach. 

PMID- 24333821
TI  - [Experience of a care pathway for psychological and behavioral symptoms of
      dementia].
AB  - Behavioral and psychological symptoms of dementia (BPSD) are present in more than
      eighty percent of patients, resulting in a significant decrease of quality of
      life of patients and caregivers. To provide the most appropriate and early
      response to behavioral disorders, a specific care pathway, unique in France, has
      been created within the Memory Center at the Hospices Civils of Lyon. It includes
      a consultation "Behavior" aimed to intervention and guidance, a Cognitive
      Behavioral Unit for pharmacological and non-pharmacological interventions in a
      comprehensive care of the patient during 3 to 4 weeks, and an Alzheimer's disease
      mobile team, which can assess the BPSD in the patient's living environment at
      home or in nursing homes, appraise drug treatments and environment, and give
      training for caregivers. This care pathway is aimed to provide individualized and
      early care for behavioral crises secondary prevention, taking into account the
      psychological, neuropsychological and somatic context of the behavioral disorders
      occurrence. 

PMID- 24333822
TI  - [Neurosyphilis and cognitive disorders].
AB  - We report the case of a 75 year old man, admitted for a delirium which was
      unusual by its severity and duration. Underlying disorders were an infectious
      disease (neurosyphilis) and prodromal Alzheimer's disease. This association was
      thought to be responsible for the delirium intensity. According to a literature
      review, we discuss the difficulties of cerebral neurosyphilis diagnosis, its
      cognitive and behavioural symptoms. We also discuss the cumulative effects of
      multi morbidities on clinical presentation, underlining a frequent problem in
      elderly patients in whom multiple causes of cognitive impairment often coexist. 

PMID- 24333823
TI  - [The aged and the test of folding a rhombus Psychometric and chronopsychological
      aspects].
AB  - This study highlights the incongruence of geriatric institutions to set up
      activities for elderly people without taking into account the circadian
      fluctuations of cognitive processes related to circadian rhythms. By example,
      rehabilitation for falls is based on the indication given by the therapist
      (instruction), its integration and assimilation by the patient (comprehension),
      and the resulting action (execution). However, the recorded information and the
      execution may present a shift of phase and even an opposition of phase. The Test
      of Folding a Rhombus (TFR) was conceived to assess the fluctuation and
      articulation of these processes. It was proposed to 60 elderly individuals
      divided into 2 groups (30 subjects with cognitive disorders - case group - and 30
      subjects without cognitive disturbance - control group -), and was applied at
      different time schedules of the day (8:00, 11:00, 15:00 and 18:00 h) once a week
      during 4 weeks. Its purpose was to quantify the relationship between automatic
      and controlled processes. Statistical analysis indicates significant circadian
      differences during the evolution of the two processes between the case and
      control groups. Simple, fast and easy to use, the TFR can also help professionals
      to choose the best automatic or controlled processes activity according to the
      need of patients. 

PMID- 24333824
TI  - [Contribution of relaxation to a psychoeducational intervention program for
      family carers of persons with Alzheimer's disease].
AB  - Family caregivers of people with Alzheimer's disease are at high risk of
      psychological and physical morbidity due to the daily caring experience.
      OBJECTIVES: to evaluate the impact of a psychoeducational program involving
      relaxation techniques on caregivers' burden and mental health status. METHODS: in
      this prospective study, 50 family caregivers were randomly assigned to one of two
      conditions: standard (CG: Control group; 12 * 90 minutes weekly sessions:
      psychoeducational group intervention) and experimental intervention (RG:
      Relaxation group; 12 * 150 minutes sessions: standard intervention + relaxation
      techniques). Caregivers' burden and mental health status were assessed using the
      Zarit burden interview (global score and three dimensions from the factor
      analysis of the French version: social consequences, psychological burden and
      feelings of guilt) and the General health questionnaire-28 at baseline, after 3
      (M3) and 6-months follow-up. Inter-individual statistics and intra-individual
      changes were calculated. RESULTS: social consequences and psychological burden
      decreased in RG. The between-group analysis showed that social consequences
      scores at M3 improved more in RG than in CG. No change in mental health was
      observed. For burden and anxiety/insomnia, intra-individual analyses showed that
      RG intervention was beneficial for more carers than CG intervention. DISCUSSION:
      this study suggests that integrating relaxation techniques into psychoeducational
      interventions is beneficial for caregivers of people with Alzheimer's disease.

PMID- 24333826
TI  - Identification of dicalcium phosphate dihydrate deposited during osteoblast
      mineralization in vitro.
AB  - The hydroxyapatite (HAP) with variable chemical substitutions has been considered
      as the major component in the mineralized part of bones. Various metastable
      crystalline phases have been suggested as transitory precursors of HAP in bone,
      but there are no consensuses as to the nature of these phases and their temporal
      evolution. In the present study, we cultured rat calvarial osteoblasts with
      ascorbate and beta-glycerophosphate to explore which calcium phosphate precursor
      phases comprise the initial mineral in the process of osteoblast mineralization
      in vitro. At the indicated time points, the deposited calcium phosphate was
      analyzed after removing organic substances from the extracellular matrix with
      hydrazine. The features comparable to dicalcium phosphate dihydrate (DCPD) and
      octacalcium phosphate (OCP), in addition to HAP, were detected in the mineral
      phases by high resolution transmission electron microscopy. And there was a trend
      of conversion from DCPD- and OCP-like phases to HAP in the course of
      mineralization, as indicated by Fourier-transform infrared microspectroscopy,
      energy-dispersive X-ray spectroscopy and synchrotron X-ray powder diffraction
      analyses. Besides, biochemical assay showed a progressive decrease in the ratio
      of mineral-associated proteins to calcium with time. These findings suggest that
      DCPD- and OCP-like phases are likely to occur on the course of osteoblast
      mineralization, and the mineral-associated proteins might be involved in
      modulating the mineral phase transformation.

PMID- 24333825
TI  - XAS spectroscopy, sulfur, and the brew within blood cells from Ascidia ceratodes.
AB  - We report the first use of K-edge X-ray absorption spectroscopy (XAS) as a direct
      spectroscopic probe of pH and cytosolic emf within living cells. A new accuracy
      metric of model-based fits to K-edge spectra is further developed. Sulfur
      functional groups in three collections of living blood cells and one sample of
      cleared blood plasma from the tunicate Ascidia ceratodes were speciated using K
      edge XAS. Cysteine and cystine, the preferred thiol-disulfide model, averaged
      about 12% of total sulfur. Sulfate monoesters and cyclic diesters unexpectedly
      constituted 36% of blood cell sulfur. Soluble sulfate averaged about 25% across
      the three blood cell samples, while the ratio of SO4(2-) to HSO4(-) implied
      average signet ring vacuolar pH values of 0.85, 1.4, or 3.1. Intracellular
      (VSO4)(+) was unobserved, while [V(RSO3)n]((3-n)+) was detected in the two lowest
      pH blood cell samples. About 5% of sulfur was distributed as mono- or
      dibenzothiophene or ethylene-epi-sulfide, or as a thiadiazole reminiscent of the
      polycarpathiamines. Blood plasma was dominated by sulfate (83%), but with 15% of
      an alkylsulfate ester and about 2% of low-valent sulfur. Gravimetric analysis of
      soluble sulfate yielded average concentrations of blood cell sulfur. Average
      [cysteine] and [cystine] (ranging ~10-30 mM and ~20-90 mM, respectively) implied
      blood-cell cytosolic emf values of approximately -0.20 V. High cellular
      [cysteine] is consistent with the proposed model for enzymatic reduction of
      vanadate by endogenous thiol, wherein the trajectory of metal site-symmetry is
      controlled and directed through to a thermodynamically favored 7-coordinate
      V(III) product.

PMID- 24333827
TI  - Therapeutic properties of VO(dmpp)2 as assessed by in vitro and in vivo studies
      in type 2 diabetic GK rats.
AB  - The bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), VO(dmpp)2, has
      shown anti-diabetic effects by in vitro studies in Wistar (W) rat adipocytes and
      in vivo in obese Zucker rats. The aim of this work is to confirm the therapeutic
      properties of VO(dmpp)2 in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. An
      in vivo study was carried out, treating W and GK rats during 21 days with a daily
      dose of VO(dmpp)2 (44 MUmol/kg). It was shown that VO(dmpp)2 doesn't affect the
      normal increase of body weight of both W and GK rats, after 8 days of treatment
      ameliorates glycemia in GK rats (8.4 +/- 0.3 vs 10.1 +/- 0.2 mM in GK control,
      P<0.001) but doesn't interfere with glucose levels in W rats and, after 21 days
      of treatment, improves the glucose intolerant profile of GK rats (13.1 +/- 0.5 vs
      20.6 +/- 0.7 mM/min in GK control, P<0.001), despite no increase of plasma
      insulin levels during glucose tolerance test. Additionally, it was demonstrated
      that VO(dmpp)2 significantly enhances [3-(3)H]-glucose uptake by W and GK rat
      adipocytes (non-toxic concentration of 100 MUM: respectively 193 +/- 20 and 254
      +/- 21%, P<0.001, relative to the basal value) showing an efficacy similar to
      insulin 1.72 nM and better than the same concentration of BMOV (P<0.01). Western
      blotting revealed that in W and GK rats VO(dmpp)2 significantly promotes IRS2
      (P<0.05) and p-AKT expression (P<0.001 and P<0.05, respectively, relative to the
      respective controls) and in GK animals reduces the increase of PTP1beta
      expression (P<0.001, relative to GK control).

PMID- 24333828
TI  - A survey of seropositivity to antigen B, an immunodiagnostic antigen for human
      cystic echinococcosis, in domestic animals in Mongolia.
AB  - Cystic echinococcosis (CE) is well known to be an important zoonotic disease and
      national disease due to the traditional nomadic life style in Mongolia. The
      present study was carried out to obtain data on the seropositivity to antigen B,
      in domestic livestock, goats, sheep and cattle, in each province of Mongolia. The
      seropositivity to antigen B varied by province and ranged from 0% to 25.0% in
      goats, 0% to 12.5% in sheep, and 0% to 13.3% in cattle. In total, 9.2% of goats,
      3.6% of sheep and 5.9% of cattle in Mongolia showed seropositivity. 

PMID- 24333830
TI  - Working memory retrieval differences between medial temporal lobe epilepsy
      patients and controls: a three memory layer approach.
AB  - Multi-store models of working memory (WM) have given way to more dynamic
      approaches that conceive WM as an activated subset of long-term memory (LTM). The
      resulting framework considers that memory representations are governed by a
      hierarchy of accessibility. The activated part of LTM holds representations in a
      heightened state of activation, some of which can reach a state of immediate
      accessibility according to task demands. Recent neuroimaging studies have studied
      the neural basis of retrieval information with different states of accessibility.
      It was found that the medial temporal lobe (MTL) was involved in retrieving
      information within immediate access store and outside this privileged zone. In
      the current study we further explored the contribution of MTL to WM retrieval by
      analyzing the consequences of MTL damage to this process considering the state of
      accessibility of memory representations. The performance of a group of epilepsy
      patients with left hippocampal sclerosis in a 12-item recognition task was
      compared with that of a healthy control group. We adopted an embedded model of WM
      that distinguishes three components: the activated LTM, the region of direct
      access, and a single-item focus of attention. Groups did not differ when
      retrieving information from single-item focus, but patients were less accurate
      retrieving information outside focal attention, either items from LTM or items
      expected to be in the WM range. Analyses focused on items held in the direct
      access buffer showed that consequences of MTL damage were modulated by the level
      of accessibility of memory representations, producing a reduced capacity. 

PMID- 24333829
TI  - Detection of circulating pancreas epithelial cells in patients with pancreatic
      cystic lesions.
AB  - Hematogenous dissemination is thought to be a late event in cancer progression.
      We recently showed in a genetic model of pancreatic ductal adenocarcinoma that
      pancreas cells can be detected in the bloodstream before tumor formation. To
      confirm these findings in humans, we used microfluidic geometrically enhanced
      differential immunocapture to detect circulating pancreas epithelial cells in
      patient blood samples. We captured more than 3 circulating pancreas epithelial
      cells/mL in 7 of 21 (33%) patients with cystic lesions and no clinical diagnosis
      of cancer (Sendai criteria negative), 8 of 11 (73%) with pancreatic ductal
      adenocarcinoma, and in 0 of 19 patients without cysts or cancer (controls). These
      findings indicate that cancer cells are present in the circulation of patients
      before tumors are detected, which might be used in risk assessment.

PMID- 24333831
TI  - Dynamic nuclear polarization using frequency modulation at 3.34 T.
AB  - During dynamic nuclear polarization (DNP) experiments polarization is transferred
      from unpaired electrons to their neighboring nuclear spins, resulting in dramatic
      enhancement of the NMR signals. While in most cases this is achieved by
      continuous wave (cw) irradiation applied to samples in fixed external magnetic
      fields, here we show that DNP enhancement of static samples can improve by
      modulating the microwave (MW) frequency at a constant field of 3.34 T. The
      efficiency of triangular shaped modulation is explored by monitoring the (1)H
      signal enhancement in frozen solutions containing different TEMPOL radical
      concentrations at different temperatures. The optimal modulation parameters are
      examined experimentally and under the most favorable conditions a threefold
      enhancement is obtained with respect to constant frequency DNP in samples with
      low radical concentrations. The results are interpreted using numerical
      simulations on small spin systems. In particular, it is shown experimentally and
      explained theoretically that: (i) The optimal modulation frequency is higher than
      the electron spin-lattice relaxation rate. (ii) The optimal modulation amplitude
      must be smaller than the nuclear Larmor frequency and the EPR line-width, as
      expected. (iii) The MW frequencies corresponding to the enhancement maxima and
      minima are shifted away from one another when using frequency modulation,
      relative to the constant frequency experiments.

PMID- 24333832
TI  - Nesfatin-1 in childhood and adolescent obesity and its association with food
      intake, body composition and insulin resistance.
AB  - Nesfatin-1 is an anorexigenic peptide that controls feeding behavior and glucose
      homeostasis. However, there is little data that exists regarding nesfatin-1
      secretion in obese children and young adolescents. The aim of this study is to
      investigate serum nesfatin-1 in childhood and adolescent obesity and to study
      potential correlations with food intake, anthropometric indices, body composition
      and insulin resistance. Forty obese children and adolescents and 40 healthy
      control subjects were studied. Anthropometric measurements were assessed, dietary
      food intake was evaluated based on 3-days food record and body composition
      indices were evaluated using bioelectrical impedance analysis. Lipid profile,
      fasting blood sugar, fasting insulin and HOMA-IR were measured. Fasting serum
      nesfatin-1 was quantitatively assayed by ELISA. Serum nesfatin-1 was
      significantly higher in obese group (2.49+/-1.96 ng/ml) than in control group
      (0.70+/-0.81 ng/ml), P=0.001. Positive correlations with serum insulin (P=0.001),
      HOMA-IR (P=0.000), BMI-SDS (P=0.04), body fat % (P=0.000), fat mass (P=0.000),
      fat free mass (P=0.03), CHO % (P=0.000), and saturated fat % (P=0.01) were found.
      While significant negative correlation with protein % (P=0.000) was observed. In
      conclusion, our results denote that nesfatin-1 might have an important role in
      regulation of food intake and pathogenesis of insulin resistance in obese
      children and young adolescents.

PMID- 24333833
TI  - Clinical predictors of psychological distress in patients presenting for
      evaluation of a spinal disorder.
AB  - BACKGROUND CONTEXT: Psychological distress has been shown to adversely affect the
      treatment outcomes of many spinal disorders. Most physicians do not routinely use
      psychological screening questionnaires. Additionally, physicians have not
      performed well when assessing patients for psychological distress while using
      clinical impression alone. PURPOSE: The purpose of our study was to evaluate the
      clinical factors that most accurately predict the presence of psychological
      distress in patients presenting for the evaluation of a spinal disorder. STUDY
      DESIGN: This is a retrospective study. PATIENT SAMPLE: Three hundred eighty-eight
      consecutive patients presented for an initial evaluation of a spinal disorder at
      a tertiary spine clinic. OUTCOME MEASURES: Oswestry disability index (ODI),
      visual analog scale (VAS), and distress risk assessment method (DRAM). METHODS:
      Three hundred eighty-eight consecutive patients presenting for the evaluation of
      a spinal disorder with a completed DRAM, ODI, and VAS were evaluated. The DRAM
      was used to classify the patients' level of psychological distress. Clinical
      variables such as history of depression, use of antidepressants, use of other
      psychotropic medications, history of surgery, and history of chronic pain
      syndromes along with ODI and VAS scores were used to develop a model to predict a
      patient's level of psychological distress. RESULTS: Our model was highly accurate
      (92%), sensitive (92%), and specific (95%) in predicting a patient's level of
      psychological distress. If patients' VAS is 4 or 5, their ODI is less than 45,
      and they are not on any psychotropic medications, they likely will fall into the
      normal group. Patients with a VAS greater than 7, currently taking
      antidepressants or other psychotropic medications, an ODI greater than 58, and a
      history of surgery are likely to fall into the higher distressed categories of
      distressed depressive or distressed somatic. CONCLUSIONS: A patient's clinical
      history, ODI, and VAS scores can predict their level of psychological distress.
      In general, patients with higher VAS pain scores, higher ODI scores (>58), and
      those taking an antidepressant or another psychotropic medication were likely to
      have high levels of psychological distress. The predictive clinical factors noted
      in this study are readily available to most physicians treating spinal disorders
      and may be helpful in improving their ability to detect patients with
      psychological distress, counseling them on realistic outcomes, and possibly
      improve their treatment outcomes.

PMID- 24333834
TI  - Object caching in corvids: incidence and significance.
AB  - Food caching is a paramount model for studying relations between cognition, brain
      organisation and ecology in corvids. In contrast, behaviour towards inedible
      objects is poorly examined and understood. We review the literature on object
      caching in corvids and other birds, and describe an exploratory study on object
      caching in ravens, New Caledonian crows and jackdaws. The captive adult birds
      were presented with an identical set of novel objects adjacent to food. All three
      species cached objects, which shows the behaviour not to be restricted to
      juveniles, food cachers, tool-users or individuals deprived of cacheable food.
      The pattern of object interaction and caching did not mirror the incidence of
      food caching: the intensely food caching ravens indeed showed highest object
      caching incidence, but the rarely food caching jackdaws cached objects to similar
      extent as the moderate food caching New Caledonian crows. Ravens and jackdaws
      preferred objects with greater sphericity, but New Caledonian crows preferred
      stick-like objects (similar to tools). We suggest that the observed object
      caching might have been expressions of exploration or play, and deserves being
      studied in its own right because of its potential significance for tool-related
      behaviour and learning, rather than as an over-spill from food-caching research.
      This article is part of a Special Issue entitled: CO3 2013. 

PMID- 24333835
TI  - Vaccination of mice with a modified Vaccinia Ankara (MVA) virus expressing the
      African horse sickness virus (AHSV) capsid protein VP2 induces virus neutralising
      antibodies that confer protection against AHSV upon passive immunisation.
AB  - In previous studies we showed that a recombinant Modified Vaccinia Ankara (MVA)
      virus expressing the protein VP2 of AHSV serotype 4 (MVA-VP2) induced virus
      neutralising antibodies in horses and protected interferon alpha receptor gene
      knock-out mice (IFNAR-/-) against challenge. We continued these studies and
      determined, in the IFNAR-/- mouse model, whether the antibody responses induced
      by MVA-VP2 vaccination play a key role in protection against AHSV. Thus, groups
      of mice were vaccinated with wild type MVA (MVA-wt) or MVA-VP2 and the antisera
      from these mice were used in a passive immunisation experiment. Donor antisera
      from (a) MVA-wt; (b) MVA-VP2 vaccinated; or (c) MVA-VP2 vaccinated and AHSV
      infected mice, were transferred to AHSV non-immune recipient mice. The recipients
      were challenged with virulent AHSV together with MVA-VP2 vaccinated and MVA-wt
      vaccinated control animals and the levels of protection against AHSV-4 were
      compared between all these groups. The results showed that following AHSV
      challenge, mice that were passively immunised with MVA-VP2 vaccinated antisera
      were highly protected against AHSV disease and had lower levels of viraemia than
      recipients of MVA-wt antisera. Our study indicates that MVA-VP2 vaccination
      induces a highly protective humoral immune response against AHSV. 

PMID- 24333836
TI  - Mutations adjacent to the end of transmembrane helices 6 and 7 independently
      affect drug efflux capacity of yeast ABC transporter Pdr5p.
AB  - As a mammalian p-glycoprotein homolog, Pdr5p is a major ATP-binding cassette
      transporter for cellular detoxification in the yeast Saccharomyces cerevisiae. In
      this study, two novel loss-of-function mutations located adjacent to the ends of
      the predicted transmembrane helices of Pdr5p were identified. C793F and S1230L
      mutations considerably impaired the transport activity of Pdr5p without affecting
      the ATPase activity and the expression level of the protein. Our results
      demonstrate that the size of residue 793 and the hydrophobicity of residue 1230
      are important for Pdr5p efflux function. It reveals that amino acid residues
      located near the end of transmembrane helix play an important role in drug efflux
      of Pdr5p. Molecular docking results further suggest that these two single
      mutations might have disturbed interactions between the drugs and Pdr5p,
      preventing the drugs from approaching the intracellular or extracellular portal
      and subsequently from being exported by Pdr5p. 

PMID- 24333837
TI  - Angiotensin II receptor blockers differentially affect CYP11B2 expression in
      human adrenal H295R cells.
AB  - We generated a stable H295R cell line expressing aldosterone synthase gene
      (CYP11B2) promoter/luciferase chimeric reporter construct that is highly
      sensitive to angiotensin II (AII) and potassium, and defined AII receptor blocker
      (ARB) effects. In the presence of AII, all ARBs suppressed AII-induced CYP11B2
      transcription. However, telmisartan alone increased CYP11B2 transcription in the
      absence of AII. Telmisartan dose-dependently increased CYP11B2 transcription/mRNA
      expression and aldosterone secretion. Experiments using CYP11B2 promoter mutants
      indicated that the Ad5 element was responsible. Among transcription factors
      involved in the element, telmisartan significantly induced NGFIB/NURR1
      expression. KN-93, a CaMK inhibitor, abrogated the telmisartan-mediated increase
      of CYP11B2 transcription/mRNA expression and NURR1 mRNA expression, but not NGFIB
      mRNA expression. NURR1 over-expression significantly augmented the telmisartan
      mediated CYP11B2 transcription, while high-dose olmesartan did not affect it.
      Taken together, telmisartan may stimulate CYP11B2 transcription via NGFIB and the
      CaMK-mediated induction of NURR1 that activates the Ad5 element, independent of
      AII type 1 receptor. 

PMID- 24333838
TI  - TGL-mediated lipolysis in Manduca sexta fat body: possible roles for lipoamide
      dehydrogenase (LipDH) and high-density lipophorin (HDLp).
AB  - Triglyceride-lipase (TGL) is a major fat body lipase in Manduca sexta. The
      knowledge of how TGL activity is regulated is very limited. A WWE domain,
      presumably involved in protein-protein interactions, has been previously
      identified in the N-terminal region of TGL. In this study, we searched for
      proteins partners that interact with the N-terminal region of TGL. Thirteen
      proteins were identified by mass spectrometry, and the interaction with four of
      these proteins was confirmed by immunoblot. The oxidoreductase lipoamide
      dehydrogenase (LipDH) and the apolipoprotein components of the lipid transporter,
      HDLp, were among these proteins. LipDH is the common component of the
      mitochondrial alpha-keto acid dehydrogenase complexes whereas HDLp occurs in the
      hemolymph. However, subcellular fractionation demonstrated that these two
      proteins are relatively abundant in the soluble fraction of fat body adipocytes.
      The cofactor lipoate found in typical LipDH substrates was not detected in TGL.
      However, TGL proved to have critical thiol groups. Additional studies with
      inhibitors are consistent with the notion that LipDH acting as a diaphorase could
      preserve the activity of TGL by controlling the redox state of thiol groups. On
      the other hand, when TG hydrolase activity of TGL was assayed in the presence of
      HDLp, the production of diacylglycerol (DG) increased. TGL-HDLp interaction could
      drive the intracellular transport of DG. TGL may be directly involved in the
      lipoprotein assembly and loading with DG, a process that occurs in the fat body
      and is essential for insects to mobilize fatty acids. Overall the study suggests
      that TGL occurs as a multi-protein complex supported by interactions through the
      WWE domain. 

PMID- 24333840
TI  - Multivariate misgivings: is D a valid measure of group and sex differences?
AB  - In the study of group and sex differences in multivariate domains such as
      personality and aggression, univariate effect sizes may underestimate the extent
      to which groups differ from one another. When multivariate effect sizes such as
      Mahalanobis D are employed, sex differences are often found to be considerably
      larger than commonly assumed. In this paper, I review and discuss recent
      criticism concerning the validity of D as an effect size in psychological
      research. I conclude that the main arguments against D are incorrect, logically
      inconsistent, or easily answered on methodological grounds. When correctly
      employed and interpreted, D provides a valid, convenient measure of group and sex
      differences in multivariate domains. 

PMID- 24333842
TI  - Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo
      oophorectomy in women with germ-line BRCA1 or BRCA2 mutations.
AB  - OBJECTIVE: This study computed the risk of clinically silent adnexal neoplasia in
      women with germ-line BRCA1 or BRCA2 mutations (BRCA(m+)) and determined
      recurrence risk. METHODS: We analyzed risk reduction salpingo-oophorectomies
      (RRSOs) from 349 BRCA(m+) women processed by the SEE-FIM protocol and addressed
      recurrence rates for 29 neoplasms from three institutions. RESULTS: Nineteen
      neoplasms (5.4%) were identified at one institution, 9.2% of BRCA1 and 3.4% of
      BRCA2 mutation-positive women. Fourteen had a high-grade tubal intraepithelial
      neoplasm (HGTIN, 74%). Mean age (54.4) was higher than the BRCA(m+) cohort
      without neoplasia (47.8) and frequency increased with age (p < 0.001). Twenty
      nine BRCA(m+) patients with neoplasia from three institutions were followed for a
      median of 5 years (1-8 years.). One of 11 with HGTIN alone (9%) recurred at 4
      years, in contrast to 3 of 18 with invasion or involvement of other sites
      (16.7%). All but two are currently alive. Among the 29 patients in the three
      institution cohort, mean ages for HGTIN and advanced disease were 49.2 and 57.7
      (p = 0.027). CONCLUSIONS: Adnexal neoplasia is present in 5-6% of RRSOs, is more
      common in women with BRCA1 mutations, and recurs in 9% of women with HGTIN alone.
      The lag in time from diagnosis of the HGTIN to pelvic recurrence (4 years) and
      differences in mean age between HGTIN and advanced disease (8.5 years) suggest an
      interval of several years from the onset of HGTIN until pelvic cancer develops.
      However, some neoplasms occur in the absence of HGTIN.

PMID- 24333844
TI  - A role for the human peroxisomal half-transporter ABCD3 in the oxidation of
      dicarboxylic acids.
AB  - Peroxisomes play a major role in human cellular lipid metabolism, including fatty
      acid beta-oxidation. Free fatty acids (FFAs) can enter peroxisomes through
      passive diffusion or by means of ATP binding cassette (ABC) transporters,
      including HsABCD1 (ALDP, adrenoleukodystrophy protein), HsABCD2 (ALDRP) and
      HsABCD3 (PMP70). The physiological functions of the different peroxisomal half
      ABCD transporters have not been fully determined yet, but there are clear
      indications that both HsABCD1 and HsABCD2 are required for the breakdown of fatty
      acids in peroxisomes. Here we report that the phenotype of the pxa1/pxa2Delta
      yeast mutant, i.e. impaired oxidation of oleic acid, cannot only be partially
      rescued by HsABCD1, HsABCD2, but also by HsABCD3, which indicates that each
      peroxisomal half-transporter can function as homodimer. Fatty acid oxidation
      measurements using various fatty acids revealed that although the substrate
      specificities of HsABCD1, HsABCD2 and HsABCD3 are overlapping, they have
      distinctive preferences. Indeed, most hydrophobic C24:0 and C26:0 fatty acids are
      preferentially transported by HsABCD1, C22:0 and C22:6 by HsABCD2 and most
      hydrophilic substrates like long-chain unsaturated-, long branched-chain- and
      long-chain dicarboxylic fatty acids by HsABCD3. All these fatty acids are most
      likely transported as CoA esters. We postulate a role for human ABCD3 in the
      oxidation of dicarboxylic acids and a role in buffering fatty acids that are
      overflowing from the mitochondrial beta-oxidation system.

PMID- 24333845
TI  - Glutamate release in the ventromedial hypothalamus of the female rat during
      copulation: modulation by estradiol.
AB  - Binding of glutamate or its ionotropic receptor agonists in the ventromedial
      hypothalamus (VMH) of female rats inhibits both appetitive and consummatory
      aspects of sexual behavior. Because vaginocervical stimulation activates
      glutamate neurons in the VMH, and administration of estradiol benzoate (EB) and
      progesterone (P) delays this effect, the present study examined the effects of
      hormonal priming on glutamate release within the VMH of female rats paired with
      sexually vigorous males. Ovariectomized, sexually experienced rats were implanted
      with guide cannula aimed at the ventrolateral VMH, through which microdialysis
      probes were inserted prior to testing. Females were assigned randomly to one of
      three hormone treatment conditions: EB+P, EB alone, or the oil vehicle. Testing
      was conducted over 5h, including a 120-min period of habituation to the testing
      chamber, a 60-min period of baseline sample collection, and a 120-min period
      during which a sexually vigorous male was introduced into the testing chamber.
      Dialysates were collected every 20min during the test and were analyzed for
      glutamate using HPLC. Females primed with oil had large and significant increases
      in glutamate release from baseline once the male was introduced to the chamber.
      Treatment with EB alone decreased glutamate release in response to male cues.
      Although treatment with EB+P did not differ significantly from EB alone, the
      degree of reduced glutamate release was less than with EB alone. These results
      indicate that priming with EB reduces glutamate transmission in the VMH in
      response to male cues. Taken together with our previous findings, estradiol
      blunts the activation of glutamate neurons in the VMH thus allowing female rats
      to copulate. 

PMID- 24333846
TI  - Thyroid hormones regulate anxiety in the male mouse.
AB  - Thyroid hormone levels are implicated in mood disorders in the adult human but
      the mechanisms remain unclear partly because, in rodent models, more attention
      has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid
      hormones act via the thyroid hormone receptor (TR) alpha and beta isoforms, both
      of which are expressed in the limbic system. TR's modulate gene expression via
      both unliganded and liganded actions. Though the thyroid hormone receptor (TR)
      knockouts and a transgenic TRalpha1 knock-in mouse have provided us valuable
      insight into behavioral phenotypes such as anxiety and depression, it is not
      clear if this is because of the loss of unliganded actions or liganded actions of
      the receptor or due to locomotor deficits. We used a hypothyroid mouse model and
      supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the
      consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our
      data from the open field and the light-dark transition tests suggest that adult
      onset hypothyroidism in male mice produces a mild anxiogenic effect that is
      possibly due to unliganded receptor actions. T3 or T4 supplementation reverses
      this phenotype and euthyroid animals show anxiety that is intermediate between
      the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not
      T4 supplemented animals have lower spine density in the CA1 region of the
      hippocampus and in the central amygdala suggesting that T3-mediated rescue of the
      hypothyroid state might be due to lower neuronal excitability in the limbic
      circuit. 

PMID- 24333847
TI  - Exposure to bisphenol-A affects fear memory and histone acetylation of the
      hippocampus in adult mice.
AB  - Bisphenol-A (BPA), an environmental endocrine disruptor, has been reported to
      possess weak estrogenic, anti-estrogenic, and anti-androgen properties. Previous
      evidence indicates that perinatal exposure to low levels of BPA affects anxiety
      like and cognitive behaviors in adult rodents. The present study aims to
      investigate the effect of BPA on emotional memory using the contextual fear
      conditioning of male mice in adulthood exposed to BPA for 90days. The results
      indicated that exposure to BPA increased the freezing time 1h and 24h after fear
      conditioning training. Furthermore, western blot analyses showed that BPA
      exposure decreased the level of N-methyl-d-aspartic acid (NMDA) receptor subunit
      NR1 and increased the expression of histone deacetylase 2 (HDAC2) before fear
      conditioning training in the hippocampus of male mice. One and twenty-four hours
      after fear conditioning training, BPA enhanced the changes of the expressions of
      NR1, phosphorylated extracellular regulated protein kinases (ERK1/2), and histone
      acetylation induced by contextual fear conditioning in the hippocampus. These
      results suggest that long term exposure to BPA enhanced fear memory by the
      concomitant increased level of NMDA receptor and/or the enhanced histone
      acetylation in the hippocampus, which may be associated with activation of ERK1/2
      signaling pathway. 

PMID- 24333843
TI  - Morphine-induced trafficking of a mu-opioid receptor interacting protein in rat
      locus coeruleus neurons.
AB  - Opiate addiction is a devastating health problem, with approximately 2million
      people currently addicted to heroin or non-medical prescription opiates in the
      United States alone. In neurons, adaptations in cell signaling cascades develop
      following opioid actions at the mu opioid receptor (MOR). A novel putative target
      for intervention involves interacting proteins that may regulate trafficking of
      MOR. Morphine has been shown to induce a re-distribution of a MOR-interacting
      protein Wntless (WLS, a transport molecule necessary for secretion of
      neurotrophic Wnt proteins), from cytoplasmic to membrane compartments in rat
      striatal neurons. Given its opiate-sensitivity and its well-characterized
      molecular and cellular adaptations to morphine exposure, we investigated the
      anatomical distribution of WLS and MOR in the rat locus coeruleus (LC)
      norepinephrine (NE) system. Dual immunofluorescence microscopy was used to test
      the hypothesis that WLS is localized to noradrenergic neurons of the LC and that
      WLS and MOR co-exist in common LC somatodendritic processes, providing an
      anatomical substrate for their putative interactions. We also hypothesized that
      morphine would influence WLS distribution in the LC. Rats received saline,
      morphine or the opiate agonist [d-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO),
      and tissue sections through the LC were processed for immunogold-silver detection
      of WLS and MOR. Statistical analysis showed a significant re-distribution of WLS
      to the plasma membrane following morphine treatment in addition to an increase in
      the proximity of gold-silver labels for MOR and WLS. Following DAMGO treatment,
      MOR and WLS were predominantly localized within the cytoplasmic compartment when
      compared to morphine and control. In a separate cohort of rats, brains were
      obtained from saline-treated or heroin self-administering male rats for pulldown
      co-immunoprecipitation studies. Results showed an increased association of WLS
      and MOR following heroin exposure. As the LC-NE system is important for cognition
      as well as decisions underlying substance abuse, adaptations in WLS trafficking
      and expression may play a role in modulating MOR function in the LC and
      contribute to the negative sequelae of opiate exposure on executive function. 

PMID- 24333849
TI  - Molecular analysis of point-of-use municipal drinking water microbiology.
AB  - Little is known about the nature of the microbiology in tap waters delivered to
      consumers via public drinking water distribution systems (DWDSs). In order to
      establish a broader understanding of the microbial complexity of public drinking
      waters we sampled tap water from seventeen different cities between the
      headwaters of the Arkansas River and the mouth of the Mississippi River and
      determined the bacterial compositions by pyrosequencing small subunit rRNA genes.
      Nearly 98% of sequences observed among all systems fell into only 5 phyla:
      Proteobacteria (35%), Cyanobacteria (29%, including chloroplasts), Actinobacteria
      (24%, of which 85% were Mycobacterium spp.), Firmicutes (6%), and Bacteroidetes
      (3.4%). The genus Mycobacterium was the most abundant taxon in the dataset,
      detected in 56 of 63 samples (16 of 17 cities). Among the more rare phylotypes,
      considerable variation was observed between systems, and was sometimes associated
      with the type of source water, the type of disinfectant, or the concentration of
      the environmental pollutant nitrate. Abundant taxa (excepting Cyanobacteria and
      chloroplasts) were generally similar from system to system, however, regardless
      of source water type or local land use. The observed similarity among the
      abundant taxa between systems may be a consequence of the selective influence of
      chlorine-based disinfection and the common local environments of DWDS and premise
      plumbing pipes. 

PMID- 24333850
TI  - A flexible approach to distributed data anonymization.
AB  - Sensitive biomedical data is often collected from distributed sources, involving
      different information systems and different organizational units. Local autonomy
      and legal reasons lead to the need of privacy preserving integration concepts. In
      this article, we focus on anonymization, which plays an important role for the re
      use of clinical data and for the sharing of research data. We present a flexible
      solution for anonymizing distributed data in the semi-honest model. Prior to the
      anonymization procedure, an encrypted global view of the dataset is constructed
      by means of a secure multi-party computing (SMC) protocol. This global
      representation can then be anonymized. Our approach is not limited to specific
      anonymization algorithms but provides pre- and postprocessing for a broad
      spectrum of algorithms and many privacy criteria. We present an extensive
      analytical and experimental evaluation and discuss which types of methods and
      criteria are supported. Our prototype demonstrates the approach by implementing k
      anonymity, l-diversity, t-closeness and delta-presence with a globally optimal de
      identification method in horizontally and vertically distributed setups. The
      experiments show that our method provides highly competitive performance and
      offers a practical and flexible solution for anonymizing distributed biomedical
      datasets. 

PMID- 24333848
TI  - Hormonal regulation of vasotocin receptor mRNA in a seasonally breeding songbird.
AB  - Behaviors associated with breeding are seasonally modulated in a variety of
      species. These changes in behavior are mediated by sex steroids, levels of which
      likewise vary with season. The effects of androgens on behaviors associated with
      breeding may in turn be partly mediated by the nonapeptides vasopressin (VP) and
      oxytocin (OT) in mammals, and vasotocin (VT) in birds. The effects of
      testosterone (T) on production of these neuropeptides have been well-studied;
      however, the regulation of VT receptors by T is not well understood. In this
      study, we investigated steroid-dependent regulation of VT receptor (VTR) mRNA in
      a seasonally breeding songbird, the white-throated sparrow (Zonotrichia
      albicollis). We focused on VTR subtypes that have been most strongly implicated
      in social behavior: V1a and oxytocin-like receptor (OTR). Using in situ
      hybridization, we show that T-treatment of non-breeding males altered V1a and OTR
      mRNA expression in several regions associated with seasonal reproductive
      behaviors. For example, T-treatment increased V1a mRNA expression in the medial
      preoptic area, bed nucleus of the stria terminalis, and ventromedial
      hypothalamus. T-treatment also affected both V1a and OTR mRNA expression in
      nuclei of the song system; some of these effects depended on the presence or
      absence of a chromosomal rearrangement that affects singing behavior, plasma T,
      and VT immunolabeling in this species. Overall, our results strengthen evidence
      that VT helps mediate the behavioral effects of T in songbirds, and suggest that
      the chromosomal rearrangement in this species may affect the sensitivity of the
      VT system to seasonal changes in T. 

PMID- 24333851
TI  - Detection of immunoglobulin isotypes from dried blood spots.
AB  - The study was designed to determine the sensitivity and reproducibility of
      recovering immunoglobulin (Ig) isotypes (IgG subclasses, IgA, IgE and IgM
      classes) from dried blood spots (DBS), a methodologic subcomponent of the Upstate
      KIDS Study. A multiplexed Luminex assay was used for IgG1/2/3/4, IgA and IgM
      analysis; an ELISA was used for IgE. Plasma samples from de-identified patients
      were used to compare the Luminex assay with nephelometry, which is routinely used
      to quantify IgA, IgG and IgM in clinical samples. The IgE ELISA was compared to
      an immunofluorescence assay. Prior to evaluation of punches from newborn dried
      blood spots (NDBSs), recoveries of Ig from punches of cord blood DBSs (CBDBSs)
      vs. plasma from the same cord bloods were compared. Although the recoveries of Ig
      from plasma and DBSs were not comparable, which could be due to cell lysates in
      the DBS samples, the analyses were reproducible. Additionally, the levels of IgA,
      IgG2, IgG4, and IgM recovered from CBDBSs positively correlated with those in
      plasma. The DBS data is a relative value since it is not equivalent to the plasma
      concentration. The majority of Ig concentrations recovered from 108 newborns of
      the Upstate KIDs Study were within the range of newborn plasma Ig levels with the
      exception of IgG3. The IgG4 values displayed the greatest variance with a wide
      range (0.01-319 mg/dl), whereas, IgG1 values had the narrowest range (85.2-960.4
      mg/dl).

PMID- 24333852
TI  - Development of a recombinant antibody towards PAPP-A for immunohistochemical use
      in multiple animal species.
AB  - The metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A), is
      increasingly recognized as a modulator of insulin-like growth factor (IGF)
      signaling; it cleaves IGF binding proteins causing the release of bioactive IGF.
      Accumulating evidence supports an important role of PAPP-A in both normal
      physiology and under different pathological conditions. However, antibodies for
      the detection of PAPP-A in non-human tissues have been lacking, although needed
      for use with several animal models which are currently being developed. To
      develop a monoclonal antibody suitable for the immunohistochemical detection of
      PAPP-A, we therefore selected a phage-derived scFv antibody, PAC1, specifically
      recognizing an epitope of PAPP-A, which is highly conserved between multiple
      animal species. We first converted this antibody into bivalent IgG, and verified
      its ability to recognize PAPP-A in sections of formalin-fixed and paraffin
      embedded tissue. For increased sensitivity, affinity maturation to sub-nanomolar
      affinity was then carried out. The resulting recombinant antibody, PAC1-D8
      mIgG2a, detects PAPP-A specifically and sensitively in human tissue. In addition,
      this antibody allows detection of PAPP-A in non-human species. We demonstrate its
      usefulness for the visualization of PAPP-A in murine and porcine tissues. 

PMID- 24333853
TI  - Polymorphism p.Val231Ile alters substrate selectivity of drug-metabolizing
      arylamine N-acetyltransferase 2 (NAT2) isoenzyme of rhesus macaque and human.
AB  - Arylamine N-acetyltransferases (NATs) are polymorphic enzymes mediating the
      biotransformation of arylamine/arylhydrazine xenobiotics, including
      pharmaceuticals and environmental carcinogens. The NAT1 and NAT2 genes, and their
      many polymorphic variants, have been thoroughly studied in humans by
      pharmacogeneticists and cancer epidemiologists. However, little is known about
      the function of NAT homologues in other primate species, including disease
      models. Here, we perform a comparative functional investigation of the NAT2
      homologues of the rhesus macaque and human. We further dissect the functional
      impact of a previously described rhesus NAT2 gene polymorphism, causing
      substitution of valine by isoleucine at amino acid position 231. Gene constructs
      of rhesus and human NAT2, bearing or lacking non-synonymous polymorphism c.691G>A
      (p.Val231Ile), were expressed in Escherichia coli for comparative enzymatic
      analysis against various NAT1- and NAT2-selective substrates. The results suggest
      that the p.Val231Ile polymorphism does not compromise the stability or overall
      enzymatic activity of NAT2. However, substitution of Val231 by the bulkier
      isoleucine appears to alter enzyme substrate selectivity by decreasing the
      affinity towards NAT2 substrates and increasing the affinity towards NAT1
      substrates. The experimental observations are supported by in silico modelling
      localizing polymorphic residue 231 close to amino acid loop 125-129, which forms
      part of the substrate binding pocket wall and determines the substrate binding
      preferences of the NAT isoenzymes. The p.Val231Ile polymorphism is the first
      natural polymorphism demonstrated to affect NAT substrate selectivity via this
      particular mechanism. The study is also the first to thoroughly characterize the
      properties of a polymorphic NAT isoenzyme in a non-human primate model. 

PMID- 24333855
TI  - Teaching tip.

PMID- 24333854
TI  - Computational identification of microRNAs in the strawberry (Fragaria x ananassa)
      genome sequence and validation of their precise sequences by miR-RACE.
AB  - In plants, microRNAs (miRNAs) play significant roles in post-transcriptional gene
      regulation and have been found to control many genes involved in different
      biological and metabolic processes. Extensive studies were carried out to
      discover miRNAs and analyze their functions in model plant species, such as in
      Arabidopsis and rice that have been reported. In this research, we used
      bioinformatics to predict microRNAs in an important strawberry rootstock cultivar
      to discover and validate precise sequences of microRNAs in strawberry. By
      adopting a range of filtering criteria, we obtained 59 potential miRNAs belonging
      to 40 miRNA families from the Fragaria vesca genome. Using two specific 5' and 3'
      miRNA RACE PCR reactions and a sequence-directed cloning method, we accurately
      determined 34 precise sequences of candidate miRNAs, while six other sequences
      exhibited some minor divergence in their termini nucleotides, and 19 miRNAs that
      could not be cloned owing to expression abundance may be too low or these mirRNAs
      predicted could not be existing in strawberry. Potential target genes were
      further predicted for the miRNAs above. The expression of the 16 miRNAs
      unreported and having exact sequences and their targets by experiment could be
      detected in different tissues of strawberry ranging from roots, stems, leaves,
      flowers and fruits by qRT-PCR and some of them showed differential expression in
      various tissues. The functional analysis of 16 miRNAs and their targets was
      carried out. Finally, we conclude that there are 34 mirRNAs in strawberry and
      their targets play vital roles not only in growth and development, but also in
      diverse physiological processes. These results show that regulatory miRNAs exist
      in agronomically important strawberry and might have an important function in
      strawberry growth and development. 

PMID- 24333856
TI  - Effect of heat stress on the expression profile of Hsp90 among Sahiwal (Bos
      indicus) and Frieswal (Bos indicus * Bos taurus) breed of cattle: a comparative
      study.
AB  - We evaluated the effect of thermal challenge on the expression profile of heat
      shock protein 90 (Hsp90) among Sahiwal (Bos indicus) and Frieswal (Bos indicus *
      Bos taurus) breeds of cattle. The present investigation was focused on the
      comparative studies on Hsp90 expression among Frieswal and Sahiwal under in vitro
      and environmental heat stress. Measured immediately after the in vitro heat shock
      to the peripheral blood mononuclear cells (PBMCs), the relative expression of
      Hsp90 mRNA was significantly (P<0.05) higher in Sahiwal compared to those in
      Frieswal. In later intervals of time, the differences in the expression levels
      between the two breeds become negligible coming down towards the basal level. A
      similar pattern was observed in the protein concentration showing significantly
      (P<0.05) higher levels in Sahiwal compared to those in Frieswal. The second sets
      of experiments were undertaken during summer months (March to May) when
      temperature peaked from 37 to 45  degrees C. During these months, Frieswal cows
      consistently recorded higher rectal temperatures than the Sahiwal breed. Further
      during this peak summer stress, Sahiwal showed significantly higher levels of
      mRNA transcripts as well as protein concentration compared to the Frieswal breed.
      Our findings also interestingly showed that, the cell viability of PBMC are
      significantly higher among the Sahiwal than Frieswal. Taken together, the
      experiments of both induced in vitro and environmental stress conditions indicate
      that, Sahiwal may express higher levels of Hsp90 then Frieswal to regulate their
      body temperature and increase cell survivality under heat stressed conditions.

PMID- 24333857
TI  - Association analysis of bovine Foxa2 gene single sequence variant and haplotype
      combinations with growth traits in Chinese cattle.
AB  - Forkhead box A2 (Foxa2) has been recognized as one of the most potent
      transcriptional activators that is implicated in the control of feeding behavior
      and energy homeostasis. However, similar researches about the effects of genetic
      variations of Foxa2 gene on growth traits are lacking. Therefore, this study
      detected Foxa2 gene polymorphisms by DNA pool sequencing, PCR-RFLP and PCR-ACRS
      methods in 822 individuals from three Chinese cattle breeds. The results showed
      that four sequence variants (SVs) were screened, including two mutations (SV1, g.
      7005 C>T and SV2, g. 7044 C>G) in intron 4, one mutation (SV3, g. 8449 A>G) in
      exon 5 and one mutation (SV4, g. 8537 T>C) in the 3'UTR. Notably, association
      analysis of the single mutations with growth traits in total individuals (at
      24months) revealed that significant statistical difference was found in four SVs,
      and SV4 locus was highly significantly associated with growth traits throughout
      all three breeds (P<0.05 or P<0.01). Meanwhile, haplotype combination CCCCAGTC
      also indicated remarkably associated to better chest girth and body weight in
      Jiaxian Red cattle (P<0.05). We herein described a comprehensive study on the
      variability of bovine Foxa2 gene that was predictive of molecular markers in
      cattle breeding for the first time. 

PMID- 24333858
TI  - Identification of quantitative trait locus (QTL) linked to dorsal fin length from
      preliminary linkage map of molly fish, Poecilia sp.
AB  - A preliminary linkage map was constructed by applying backcross and testcross
      strategy using microsatellite (SSR) markers developed for Xiphophorus and
      Poecilia reticulata in ornamental fish, molly Poecilia sp. The linkage map having
      18 SSR loci consisted of four linkage groups that spanned a map size of 516.1cM.
      Association between genotypes and phenotypes was tested in a random fashion and
      QTL for dorsal fin length was found to be linked to locus Msb069 on linkage group
      2. Coincidentally, locus Msb069 was also reported as putative homologue primer
      pairs containing SSRs repeat motif which encoded hSMP-1, a sex determining locus.
      Dorsal fin length particularly in males of Poecilia latipinna is an important
      feature during courtship display. Therefore, we speculate that both dorsal fin
      length and putative hSMP-1 gene formed a close proximity to male sexual
      characteristics. 

PMID- 24333859
TI  - Structure and mechanism of Escherichia coli type I signal peptidase.
AB  - Type I signal peptidase is the enzyme responsible for cleaving off the amino
      terminal signal peptide from proteins that are secreted across the bacterial
      cytoplasmic membrane. It is an essential membrane bound enzyme whose
      serine/lysine catalytic dyad resides on the exo-cytoplasmic surface of the
      bacterial membrane. This review discusses the progress that has been made in the
      structural and mechanistic characterization of Escherichia coli type I signal
      peptidase (SPase I) as well as efforts to develop a novel class of antibiotics
      based on SPase I inhibition. This article is part of a Special Issue entitled:
      Protein trafficking and secretion in bacteria. Guest Editors: Anastassios
      Economou and Ross Dalbey. 

PMID- 24333860
TI  - Glucose-induced dissociation of glucokinase from its regulatory protein in the
      nucleus of hepatocytes prior to nuclear export.
AB  - The glucose phosphorylating enzyme glucokinase regulates glucose metabolism in
      the liver. Glucokinase activity is modulated by a liver-specific competitive
      inhibitor, the glucokinase regulatory protein (GRP), which mediates sequestration
      of glucokinase to the nucleus at low glucose concentrations. However, the
      mechanism of glucokinase nuclear export is not fully understood. In this study we
      investigated the dynamics of glucose-dependent interaction and translocation of
      glucokinase and GRP in primary hepatocytes using fluorescence resonance energy
      transfer, selective photoconversion and fluorescence recovery after
      photobleaching. The formation of the glucokinase:GRP complex in the nucleus of
      primary hepatocytes at 5 mmol/l glucose was significantly reduced after a 2 h
      incubation at 20 mmol/l glucose. The GRP was predominantly localized in the
      nucleus, but a mobile fraction moved between the nucleus and the cytoplasm. The
      glucose concentration only marginally affected GRP shuttling. In contrast, the
      nuclear export rate of glucokinase was significantly higher at 20 than at 5
      mmol/l glucose. Thus, glucose was proven to be the driving-force for nuclear
      export of glucokinase in hepatocytes. Using the FLII2Pglu-700mu-delta6 glucose
      nanosensor it could be shown that in hepatocytes the kinetics of nuclear glucose
      influx, metabolism or efflux were significantly faster compared to insulin
      secreting cells. The rapid equilibration kinetics of glucose flux into the
      nucleus facilitates dissociation of the glucokinase:GRP complex and also nuclear
      glucose metabolism by free glucokinase enzyme. In conclusion, we could show that
      a rise of glucose in the nucleus of hepatocytes releases active glucokinase from
      the glucokinase:GRP complex and promotes the subsequent nuclear export of
      glucokinase.

PMID- 24333861
TI  - First case of drug rash eosinophilia and systemic symptoms due to boceprevir.
AB  - Boceprevir and telaprevir are 2 specific inhibitors of the hepatitis C (HCV)
      serine protease 3. Cutaneous side effects have been reported with high frequency,
      essentially rash, and dry skin. We report a case of drug rash with eosinophilia
      and systemic symptoms (DRESS) due to boceprevir. A 56-year-old African woman with
      chronic hepatitis C complicated with cirrhosis and cryoglobulinemia received
      pegylated interferon alfa-2a (PegIFN) and ribavirin (RBV) for 4 weeks and then
      boceprevir was added. She was also co-infected with HIV state A2. Eight weeks
      after adding boceprevir she developed a generalized maculopapular exanthema with
      fever, facial oedema, apparition of lymph node and alteration of the general
      state. She presented an eosinophilia (up to 3.0 * 10(9)cells/L), no biological
      inflammatory syndrome. The computed tomography revealed several lymph nodes
      located in the abdominal and inguinal areas. The cutaneous biopsy was consistent
      with a drug rash reaction. The HCV treatment was stopped and the patient was
      treated with topical steroids. Cutaneous and systemic symptoms disappeared in few
      weeks. Boceprevir was considered the culprit drug. We report to our knowledge the
      first case of DRESS due to boceprevir.

PMID- 24333863
TI  - A new look on liver anatomy: needs and means to go beyond the Couinaud scheme.

PMID- 24333862
TI  - A population-based study on the prevalence of NASH using scores validated against
      liver histology.
AB  - BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a leading cause of
      chronic liver disease in Western countries. Diagnosis of NASH requires a liver
      biopsy. We estimated the prevalence of NASH non-invasively in a population-based
      study using scores validated against liver histology. METHODS: Clinical
      characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments
      were measured in 296 consecutive bariatric surgery patients who underwent a liver
      biopsy to discover and validate a NASH score ('NASH score'). We also defined the
      cut-off for NASH for a previously validated NAFLD liver fat score to diagnose
      NASH in the same cohort ('NASH liver fat score'). Both scores were validated in
      an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who
      had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish
      population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate
      the population prevalence of NASH. RESULTS: The final 'NASH Score' model included
      PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774
      (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for
      'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787),
      respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of
      NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%).
      Sensitivity analysis was performed by taking into account stochastic false
      positivity and false-negativity rates in a Bayesian model. This analysis yielded
      population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using
      'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'. CONCLUSIONS: The
      population prevalence of NASH in 45-74 year old Finnish subjects is ~ 5%.

PMID- 24333864
TI  - Reduced autobiographical memory specificity relates to weak resistance to
      proactive interference.
AB  - BACKGROUND AND OBJECTIVES: Reduced autobiographical memory specificity (rAMS),
      experiencing intrusive memories, and rumination appear to be risk factors for
      depression and depressive relapse. The aim of the current study was to
      investigate whether a weak resistance to proactive interference (PI) might
      underlie this trio of cognitive risk factors. Resistance to PI refers to being
      able to ignore cognitive distracters that were previously relevant but became
      irrelevant for current task goals. METHOD: Students (N = 65) and depressed
      patients (N = 37) completed tasks measuring resistance to PI and AMS, and
      completed questionnaires on intrusive memories and rumination. RESULTS: In both
      samples, weaker resistance to PI was associated with rAMS. There was no evidence
      for a relationship between resistance to PI and intrusive memories or rumination.
      LIMITATIONS: As we did not assess other measures of executive functioning, we
      cannot conclude whether the observed relationship between rumination and PI is
      due to unique qualities of PI. CONCLUSIONS: Difficulties to deliberately recall
      specific, rather than general or categoric autobiographical memories appear to be
      related to more general problems with the inhibition of interference of mental
      distracters. The results are in line with the executive control account of rAMS.

PMID- 24333865
TI  - Dexamethasone exacerbates cerebral edema and brain injury following lithium
      pilocarpine induced status epilepticus.
AB  - Anti-inflammatory therapies are the current most plausible drug candidates for
      anti-epileptogenesis and neuroprotection following prolonged seizures. Given that
      vasogenic edema is widely considered to be detrimental for outcome following
      status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used
      in clinic for alleviating cerebral edema. In this study we perform longitudinal
      magnetic resonance imaging in order to assess the contribution of dexamethasone
      on cerebral edema and subsequent neuroprotection following status epilepticus.
      Lithium-pilocarpine was used to induce status epilepticus in rats. Following
      status epilepticus, rats were either post-treated with saline or with
      dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by
      means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry
      was used as a marker of neuronal injury. T2 relaxometry was performed prior to,
      48 h and 96 h following status epilepticus. Volume measurements were performed
      between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was
      worse in rats that were treated with dexamethasone compared to controls.
      Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to
      controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4
      days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally,
      the mortality rate in the first week following status epilepticus increased from
      14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg
      dexamethasone respectively. These findings suggest that dexamethasone can
      exacerbate the acute cerebral edema and brain injury associated with status
      epilepticus.

PMID- 24333866
TI  - Comparison of in vitro toxicity of mainstream cigarette smoke particulate matter
      from nano- to micro-size.
AB  - In order to investigate the interrelationship between particulate matter (PM)
      size and in vitro toxicological effects of mainstream cigarette smoke, PM sized
      between 10 nm and 10 MUm in mainstream cigarette smoke was sampled and divided
      into six stages. The in vitro cytotoxicity, genotoxicity and cell inhibition
      effects of PM were assessed by the neutral red cytotoxicity assay, Salmonella
      mutagenicity assay, micronucleus test and flow cytometry analysis, respectively.
      The results showed that all test samples were cytotoxic in the neutral red
      cytotoxicity assay. The IC50 values in the small-sized groups were significantly
      lower than those in the large-sized groups. Most test samples were mutagenic in
      the Salmonella mutagenicity assay (TA98 with S9 and TA100 with S9) and increased
      the frequency of micronucleated cells. Most PM disturbed the normal progression
      of the cell cycle, resulting in the accumulation of cells in the G0/G1 phase and
      the induction of apoptosis. In these tests, PM of a large size induced less
      toxicity compared with PM of a small size. These findings suggest that most PM
      samples induced toxicity in vitro, and PM of a small size was more toxic than PM
      of a large size.

PMID- 24333867
TI  - A 3-week dietary bioequivalence study in preweaning farm piglets of two sources
      of docosahexaenoic acid produced from two different organisms.
AB  - Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are components of human
      breast milk and commonly added to infant formula. The first DHA-containing algal
      oil for infant formulas was DHASCO(r) produced from the microalgae
      Crypthecodinium cohnii. Recently, new DHA-rich oil was obtained from the
      microalgae Schizochytrium sp., herein named DHASCO-B. The objectives of this
      study were to evaluate the bioequivalence of DHASCO-B to DHASCO when administered
      in a blend with ARA oil and the potential effects after 3weeks' administration in
      milk replacer formula to preweaning farm piglets. DHASCO-B and DHASCO were added
      to formula at concentrations 0.32% and 0.96% DHA (% of total fatty acids). There
      were no test article-related effects of any diet on piglet growth and development
      (clinical observations, body weight, food consumption), or clinical pathology
      parameters (hematology, clinical chemistry, coagulation and urinalysis). In
      addition, there were no adverse effects at terminal necropsy (macro- and
      microscopic pathology evaluations). DHA content in plasma, RBC, heart, liver and
      brain showed dose-related accumulation and confirmed no differences between
      corresponding DHASCO-B and DHASCO groups. Therefore, dietary exposure to DHASCO-B
      and DHASCO was well tolerated by the preweaning piglets during the 3-week dosing
      period right after birth and DHASCO-B and DHASCO were bioequivalent. 

PMID- 24333868
TI  - AKT signaling is involved in fucoidan-induced inhibition of growth and migration
      of human bladder cancer cells.
AB  - We identified a novel mechanism of AKT signaling in the fucoidan-induced
      proliferation and migration of human urinary 5637 cancer cells. Fucoidan
      treatment showed a significant growth inhibition followed by G1-phase-associated
      up-regulation of p21WAF1 expression and suppression of cyclins and CDK expression
      in 5637 cells. Also, fucoidan treatment induced the activation of AKT signaling,
      which was inhibited by treatment with wortmannin, a PI3K-specific inhibitor.
      Blockade of the AKT function reversed the fucoidan-mediated inhibition of cell
      proliferation, the increased G1-phase-associated p21WAF1 expression, and the
      reduction of cell-cycle proteins. Moreover, treatment with fucoidan blocked
      migration and invasion of 5637 cells. This inhibition was attributed to decreased
      expression of MMP-9, which was mediated by down-regulation of AP-1 and NF-kappaB
      binding activity. Furthermore, wortmannin treatment abolished the decreased cell
      migration and invasion and the inhibition of MMP-9 expression via the suppression
      of NF-kappaB and AP-1 in fucoidan-treated cells. Similar results were observed in
      another bladder cancer T-24 cells treated with fucoidan. Finally, overexpression
      of the AKT gene inhibited the proliferation, migration and invasion of bladder
      cancer cells. These data suggest that the activation of AKT signaling is involved
      in growth inhibition and suppression of the migration and invasion of bladder
      cancer cells treated with fucoidan. 

PMID- 24333869
TI  - Non-targeted radiation effects in vivo: a critical glance of the future in
      radiobiology.
AB  - Radiation-induced bystander effects (RIBE), demonstrate the induction of
      biological non-targeted effects in cells which have not directly hit by radiation
      or by free radicals produced by ionization events. Although RIBE have been
      demonstrated using a variety of biological endpoints the mechanism(s) of this
      phenomenon still remain unclear. The controversial results of the in vitro RIBE
      and the evidence of non-targeted effects in various in vivo systems are
      discussed. The experimental evidence on RIBE, indicate that a more analytical and
      mechanistic in depth approach is needed to secure an answer to one of the most
      intriguing questions in radiobiology. 

PMID- 24333870
TI  - Generation of functional endothelial-like cells from adult mouse germline-derived
      pluripotent stem cells.
AB  - Functional endothelial cells and their progenitors are required for vascular
      development, adequate vascular function, vascular repair and for cell-based
      therapies of ischemic diseases. Currently, cell therapy is limited by the low
      abundance of patient-derived cells and by the functional impairment of autologous
      endothelial progenitor cells (EPCs). In the present study, murine germline
      derived pluripotent stem (gPS) cells were evaluated as a potential source for
      functional endothelial-like cells. Cells displaying an endothelial cell-like
      morphology were obtained from gPS cell-derived embryoid bodies using a
      combination of fluorescence-activated cell sorting (FACS)-based selection of CD31
      positive cells and their subsequent cultivation on OP9 stromal cells in the
      presence of VEGF-A. Real-time reverse transcriptase polymerase chain reaction,
      FACS analysis and immunofluorescence staining showed that the gPS cell-derived
      endothelial-like cells (gPS-ECs) expressed endothelial cell-specific markers
      including von Willebrand Factor, Tie2, VEGFR2/Flk1, intercellular adhesion
      molecule 2 and vascular endothelial-cadherin. The high expression of ephrin B2,
      as compared to Eph B4 and VEGFR3, suggests an arterial rather than a venous or
      lymphatic differentiation. Their capability to take up Dil-conjugated acetylated
      low-density lipoprotein and to form capillary-like networks on matrigel confirmed
      their functionality. We conclude that gPS cells could be a novel source of
      endothelial cells potentially suitable for regenerative cell-based therapies for
      ischemic diseases. 

PMID- 24333871
TI  - A supra-cellular model for coupling of bone resorption to formation during
      remodeling: lessons from two bone resorption inhibitors affecting bone formation
      differently.
AB  - The bone matrix is maintained functional through the combined action of bone
      resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling
      units. The coupling of these two activities is critical for securing bone
      replenishment and involves osteogenic factors released by the osteoclasts.
      However, the osteoclasts are separated from the mature bone forming osteoblasts
      in time and space. Therefore the target cell of these osteoclastic factors has
      remained unknown. Recent explorations of the physical microenvironment of
      osteoclasts revealed a cell layer lining the bone marrow and forming a canopy
      over the whole remodeling surface, spanning from the osteoclasts to the bone
      forming osteoblasts. Several observations show that these canopy cells are a
      source of osteoblast progenitors, and we hypothesized therefore that they are the
      likely cells targeted by the osteogenic factors of the osteoclasts. Here we
      provide evidence supporting this hypothesis, by comparing the osteoclast-canopy
      interface in response to two types of bone resorption inhibitors in rabbit lumbar
      vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone
      formation levels, reduces the extent of canopy coverage above osteoclasts. This
      effect is in accordance with its toxic action on periosteoclastic cells. In
      contrast, odanacatib, an inhibitor preserving bone formation, increases the
      extent of the osteoclast-canopy interface. Interestingly, these distinct effects
      correlate with how fast bone formation follows resorption during these respective
      treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to
      bind the collagen made available by osteoclasts, and reported to mediate
      osteoblast recruitment. Overall these observations support a mechanism where the
      recruitment of bone forming osteoblasts from the canopy is induced by
      osteoclastic factors, thereby favoring initiation of bone formation. They lead to
      a model where the osteoclast-canopy interface is the physical site where coupling
      of bone resorption to bone formation occurs. 

PMID- 24333872
TI  - Steroid hormones are novel nucleoside transport inhibitors by competition with
      nucleosides for their transporters.
AB  - Nucleoside transport is important for nucleic acid synthesis in cells that cannot
      synthesize nucleosides de novo, and for entry of many cytotoxic nucleoside analog
      drugs used in chemotherapy. This study demonstrates that various steroid hormones
      induce inhibition of nucleoside transport in mammalian cells. We analyzed the
      inhibitory effects of estradiol (E2) on nucleoside transport using SH-SY5Y human
      neuroblastoma cells. We observed inhibitory effects after acute treatment with
      E2, which lasted in the presence of E2. However, when E2 was removed, the effect
      immediately disappeared, suggesting that E2 effects are not mediated through the
      canonical regulatory pathway of steroid hormones, such as transcriptional
      regulation. We also discovered that E2 could competitively inhibit thymidine
      uptake and binding of the labeled nucleoside transporter inhibitor, S-[4
      nitrobenzyl]-6-thioinosine (NBTI), indicating that E2 binds to endogenous
      nucleoside transporters, leading to inhibition of nucleoside transport. We then
      tested the effects of various steroids on nucleoside uptake in NBTI-sensitive
      cells, SH-SY5Y and NBTI-insensitive cells H9c2 rat cardiomyoblasts. We found E2
      and progesterone clearly inhibited both NBTI-sensitive and insensitive uptake at
      micromolar concentrations. Taken together, we concluded that steroid hormones
      function as novel nucleoside transport inhibitors by competition with nucleosides
      for their transporters. 

PMID- 24333873
TI  - Baclofen, a GABAB receptor agonist, enhances ubiquitin-proteasome system
      functioning and neuronal survival in Huntington's disease model mice.
AB  - Huntington's disease (HD) is an autosomal neurodegenerative disease. Its
      manifestations is selective degeneration of medium-sized spiny neurons (MSN) in
      the striatum. The specificity of the vulnerability of these GABAergic MSNs can be
      explained by abnormal protein accumulation, excitotoxicity, mitochondrial
      dysfunction, and failure of trophic control, among other dysfunctions. In this
      study, we used in vitro and in vivo models of HD to study the effects of
      GABAergic neuron stimulation on the cellular protein degradation machinery. We
      administered the GABA(B) receptor agonist, baclofen, to wild-type or mutant
      huntingtin-expressing striatal cells (HD19 or HD43). Chymotrypsin-like proteasome
      activity and cell viability were significantly increased in the mutant huntingtin
      expressing striatal cells (HD43) after GABA(B) receptor agonist treatment. In
      addition, we systemically administered baclofen to a HD model containing the
      entire human huntingtin gene with 128 CAG repeats (YAC128). Chymotrypsin-like
      proteasome activity was significantly increased in YAC128 transgenic mice after
      baclofen administration. Baclofen-injected mutant YAC128 mice also showed
      significantly reduced numbers of ubiquitin-positive neuronal intranuclear
      inclusions (NIIs) in the striatum. Baclofen markedly improved behavioral
      abnormalities in mutant YAC128 mice as determined by the rotarod performance
      test. These data indicate that stimulation of GABAergic neurons with the GABAB
      receptor agonist, baclofen, enhances ubiquitin-proteasome system (UPS) function
      and cell survival in in vitro and in vivo models of HD.

PMID- 24333874
TI  - Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal
      carcinoma cell in vitro and suppresses tumor growth in vivo.
AB  - Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been
      shown to induce cell death in various human cancer cells. However, whether
      salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not
      been determined to date. The present study investigated the chemotherapeutic
      efficacy of salinomycin and its molecular mechanisms of action in NPC cells.
      Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines
      (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is
      accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial
      membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor
      lipoprotein receptor related protein 6 (LRP6) and beta-catenin was down
      regulated, which showed that the Wnt/beta-catenin signaling was involved in
      salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model,
      the anti-tumor effect of salinomycin was associated with the downregulation of
      beta-catenin expression. The present study demonstrated that salinomycin can
      effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells
      in vitro and inhibit tumor growth in vivo, probably via the inhibition of
      Wnt/beta-catenin signaling, suggesting salinomycin as a potential candidate for
      the chemotherapy of NPC. 

PMID- 24333875
TI  - From expert-derived user needs to user-perceived ease of use and usefulness: a
      two-phase mixed-methods evaluation framework.
AB  - Underspecified user needs and frequent lack of a gold standard reference are
      typical barriers to technology evaluation. To address this problem, this paper
      presents a two-phase evaluation framework involving usability experts (phase 1)
      and end-users (phase 2). In phase 1, a cross-system functionality alignment
      between expert-derived user needs and system functions was performed to inform
      the choice of "the best available" comparison system to enable a cognitive
      walkthrough in phase 1 and a comparative effectiveness evaluation in phase 2.
      During phase 2, five quantitative and qualitative evaluation methods are mixed to
      assess usability: time-motion analysis, software log, questionnaires - System
      Usability Scale and the Unified Theory of Acceptance of Use of Technology, think
      aloud protocols, and unstructured interviews. Each method contributes data for a
      unique measure (e.g., time motion analysis contributes task-completion-time;
      software log contributes action transition frequency). The measures are
      triangulated to yield complementary insights regarding user-perceived ease-of
      use, functionality integration, anxiety during use, and workflow impact. To
      illustrate its use, we applied this framework in a formative evaluation of a
      software called Integrated Model for Patient Care and Clinical Trials (IMPACT).
      We conclude that this mixed-methods evaluation framework enables an integrated
      assessment of user needs satisfaction and user-perceived usefulness and usability
      of a novel design. This evaluation framework effectively bridges the gap between
      co-evolving user needs and technology designs during iterative prototyping and is
      particularly useful when it is difficult for users to articulate their needs for
      technology support due to the lack of a baseline. 

PMID- 24333877
TI  - Editorial.

PMID- 24333876
TI  - How many "Get Screened" messages does it take? Evidence from colorectal cancer
      screening promotion in the United States, 2012.
AB  - OBJECTIVE: Colorectal cancer screening has been widely promoted in the United
      States. We investigated the association between reported exposure to screening
      information during the past year and screening participation and knowledge.
      METHOD: Data from the 2012 HealthStyles Fall survey of U.S. adults were examined
      using adjusted logistic regression to examine the frequency of exposure to
      screening information as a predictor of screening participation and knowledge;
      analyses were limited to participants aged >=50years with no history of
      colorectal cancer or polyps (N=1714). RESULTS: Nearly half of the participants
      (44.9%) reported exposure to colorectal cancer screening information during the
      previous year. The most common sources of screening information were news
      reports, advertisements, and health care providers. Screening participation and
      knowledge consistently increased with the reported frequency of exposure to
      screening information, and these associations generally persisted when
      demographic variables were controlled. Compared with unexposed participants,
      significant gains in screening participation were associated with exposure to
      screening information 2-3 times (Adj. OR=1.84, p=0.001), 4-9 times (Adj. OR=2.00,
      p=0.001), and >=10 times (Adj. OR=3.03, p<0.001) in the adjusted model.
      CONCLUSIONS: Increasing public exposure to screening promotion messages may
      augment screening participation and knowledge.

PMID- 24333878
TI  - SUNY downstate.

PMID- 24333879
TI  - Brain Imaging and tinnitus.

PMID- 24333880
TI  - Textbook of vertigo: diagnosis and management.

PMID- 24333881
TI  - Experiences with complex vestibular rehabilitation.
AB  - INTRODUCTION: Vestibular rehabilitation of patients suffering from balance
      disorders is a long and difficult process, the exact cause of therapeutic success
      or failure remains often unknown. In our practice, the complex vestibular
      rehabilitation consists of medical treatment and rehabilitation training program.
      Balance training comprises mostly statokinetic exercises, however, the training
      of the vestibulo-ocular pathways are as important as of the vestibulospinal
      pathways. PATIENTS: The author used training exercises for the vestibulo-ocular
      and vestibulospinal pathways in patients who were treated with parenteral and
      oral vasoactive drugs. METHODS: For measuring the improvement of the patients, a
      modified Dizziness Handicap Inventory questionnaire was used. RESULTS: The
      results show that the vasoactive medical treatment combined with optokinetic
      training improved the patients' condition. Our findings suggest that psychiatric
      status of the patients influences the outcome of the treatment. CONCLUSIONS:
      Medical treatment combined with optokinetic and statokinetic training program is
      effective in the rehabilitation of dizzy patients and improves the quality of
      life.

PMID- 24333882
TI  - Development and standardization of tinnitus handicap inventory in Kannada.
AB  - INTRODUCTION: Tinnitus Handicap Inventory (THI) was developed in English to
      quantify the handicap caused due to tinnitus. According to a survey conducted by
      USA, 40 million people are affected by tinnitus. OBJECTIVES: India being a
      multilingual country needs to develop and standardize THI in Indian languages.
      The present study concentrates on Developing and Standardizing THI in Kannada.
      MATERIALS AND METHODS: Questions from English version of THI were translated and
      modified by two professionals who have a degree of MA Kannada. Translated
      inventory was given to 50 native Kannada speakers for the familiarity check & the
      most familiar sentences were included in the study. Tinnitus questionnaire was
      then administered, followed by the Kannada version of THI on 140 patients and
      total scores were obtained. RESULTS: Analysis revealed 14% of the patients fall
      under the category of Slight, 38% under Mild, 26% under Moderate, 16% under
      Severe and 6% under Catastrophic group. An item total correlation and Cronbach
      alpha test was administered to examine the reliability measures and the scores
      were 0.883 and 0.885 on standardized item. CONCLUSION: Scores of Cronbach-alpha
      test shows that Kannada version of THI is a standard and reliable tool for
      measuring the handicap caused by tinnitus and can successfully classify
      individuals on a severity basis.

PMID- 24333883
TI  - Impact of visual disorders on vestibular and balance rehabilitation therapy
      outcomes in soldiers with blast injury.
AB  - INTRODUCTION: One of the standard measurements in the evaluation process is
      quantifying the tinnitus frequency. With advancements in the treatments of
      tinnitus, the need for a simple patient-directed automated tinnitus assessment is
      urging. OBJECTIVES: To investigate the accuracy of a web-based protocol for
      tinnitus frequency matching in comparison to audiometry. MATERIALS AND METHODS:
      Twenty subjects had tinnitus frequency matching in a random order using an
      audiometer in an anechoic chamber and using a web-based software with a multiple
      choice protocol and a slider. Octave challenge testing was performed.
      Participants were asked to indicate which protocol resulted in the closest match
      to their tinnitus frequency. RESULTS: Median tinnitus frequency was 6000Hz
      (range, 2000-12000Hz) using the audiometer and self-directed multiple-choice
      protocol. Using the slider, the median frequency was 5925Hz (range, 1850
      16000Hz). The patients with tinnitus frequency of over 12000Hz experienced a
      higher level of satisfaction when using the computer-based slider system. Five
      patients experienced octave confusion with self-directed multiple-choice tinnitus
      matching that was corrected accurately after the octave challenge step.
      CONCLUSION: A web-based protocol for tinnitus frequency matching is as accurate
      as a standard audiometric protocol. An octave challenge test is necessary for a
      patient-directed tinnitus frequency matching.

PMID- 24333884
TI  - Tinnitus and quality of life after round window vibroplasty.
AB  - OBJECTIVE: To measure the Quality of Life outcomes and impact on tinnitus
      perception in a group of patients after Round Window Vibroplasty (RW-VSB) for
      mixed or conductive hearing loss. STUDY DESIGN: A single-subject, repeated
      measures design was employed. All VSB fittings were based on hearing thresholds
      results and were not set to mask tinnitus. METHODS: Ten Round Window-Vibroplasty
      patients were assessed with the Abbreviated Profile of Hearing Aid Benefit
      (APHAB) and the Tinnitus Reaction Questionnaire (TRQ). RESULTS: Subjects reported
      less hearing difficulties in 3 of 4 APHAB subscales. Tinnitus perception was
      decreased in all subjects with tinnitus pre-operatively. CONCLUSION: Round window
      vibroplasty in our cohort of patients with mixed or conductive hearing improved
      quality of life outcomes. There was significant improvement on APHAB scores and a
      significant decrease in tinnitus perception in subjects experiencing tinnitus
      prior to implantation.

PMID- 24333885
TI  - Ancient voices on tinnitus: the pathology and treatment of tinnitus in Celsus and
      the Hippocratic Corpus compared and contrasted.
AB  - OBJECTIVE: The object of the paper is to analyse the treatment of tinnitus in two
      ancient works, Celsus De Medicina and the Greek Hippocratic Corpus. Whilst
      reviews of historical references to tinnitus have identified this material, this
      is the first detailed treatment of the subject in these authors. DESIGN: The
      paper considers the material relating to tinnitus and suggested treatments in the
      Roman medical writer Celsus (mid first century AD) in contrast with those found
      in the Greek Hippocratic Corpus (late fifth, early fourth century BC). RESULTS
      AND CONCLUSION: The lifestyle change, diet and pharmacological treatments
      suggested by Celsus are analysed and shown as likely to be effective. Celsus is
      shown to be remarkably modern in his understanding of the aetiology of the
      disease and his suggested dietary and pharmacological treatments appear to be
      soundly based. Celsus' pharmacological approach differs from the more theoretical
      stance of the Hippocratic Corpus based on humoural theory. The Hippocratric
      Corpus is more detailed in its descriptions of otological pathology and more
      concerned with a humoural explanation of the disease, but offers useful advice on
      diet and regimen and also provides the first detailed description of what appears
      to be Meniere's Syndrome.

PMID- 24333886
TI  - National linguistic validation of the Tinnitus Handicap Inventory (THI).
      Assessment of disability caused by tinnitus in Chilean Spanish-speaking
      population.
AB  - INTRODUCTION: The psycho-emotional assessment is of utmost importance for
      evaluation of patients with tinnitus. The Tinnitus Handicap Inventory (THI), is
      the most known and validated test for this purpose. OBJECTIVES: We propose a
      linguistic validation of the THI, in order to obtain reliable answers in our
      country. MATERIALS AND METHODS: We performed a translation of the original
      English questionnaire and assessed its feasibility by applying it in a group of
      patients with tinnitus. Statistical analysis included internal validity
      (Cronbach's alpha) and linear correlation tests (Pearson coefficient). RESULTS:
      We evaluated 60 patients with a mean age of 59 years. We obtained a Cronbach's
      alpha index of 0.97 for the whole questionnaire. CONCLUSIONS: The adapted version
      of the THI shows satisfactory levels of internal consistency for the assessment
      of disability caused by tinnitus.

PMID- 24333887
TI  - An electrophysiological approach to tinnitus interpretation.
AB  - INTRODUCTION: Serotonin seems to play a central role in tinnitus. The intensity
      dependence of auditory evoked potential (IDAP) is considered an index of central
      serotonergic activity in the auditory cortex. The higher the steepness of the
      N1/P2 component amplitude-stimulus function slope (N1/P2 ASF slope as calculated
      by IDAP), the lower the central serotonergic activity. Similarly, the N1
      amplitude-stimulus function slope (N1 ASF slope) was investigated. Auditory
      brainstem responses (ABR) examine the auditory system functionality from the
      periphery and through the brainstem, where serotonergic projections have been
      identified. OBJECTIVES: Assessing whether tinnitus perception neurotransmitters
      activity inbalance could be investigated by an electrophysiological approach.
      MATERIALS AND METHODS: Ten normoacousic tinnitus patients and 14 healthy controls
      were included in the study. Subjects underwent EEG (IDAP) recording, ABR
      recording and psychometric questionnaires administration. RESULTS: N1/P2 ASF
      slope and N1ASF slope tended to have a greater steepness in patients. N1ASF slope
      was significantly correlated with ABR wave V and interpeak III-V latencies in
      patients. ABR wave V and interpeak III-V latencies were significantly longer in
      patients than in controls. CONCLUSION: N1/P2 ASF slope, N1 ASF slope and ABR
      components appear to be useful electrophysiologic methods to study possible
      functional alterations related to the serotonergic activity.

PMID- 24333888
TI  - Auditory Brainstem Responses (ABR) changes in children treated with high doses
      cisplatin.
AB  - INTRODUCTION: Cisplatin can cause cochlear damage by oxidative stress in hair
      cells, but there are few studies regarding toxicity in the central auditory
      pathways. OBJECTIVE: To study cisplatin neurotoxicity in the central auditory
      pathways in children treated with high doses cisplatin for solid malignant
      tumors. METHODS: Thirteen children (Group S) aged 3-19 years who had been treated
      with cisplatin (60-120 mg/m(2)/cycle) were studied using evoked otoacoustic
      emissions (EOA), conventional auditory evaluation and auditory brainstem response
      (ABR). Thirteen normal children matched for age and sex composed the control
      group (Group C). RESULTS: Group S - 7.5% percent of ears showed enlargement of
      latencies of waves I and V, and 3.8% of wave III. Six ears (23%) showed enlarged
      interpeak intervals. Four ears showed increased interpeak I-III and two showed
      increased interpeak III-V. The results were compared using the Mann-Whitney test.
      Interpeak III-V differed significantly between groups S and C when only the left
      ears were considered. EOA results were normal in both groups.
      DISCUSSION/CONCLUSION: Abnormal values in the interpeak I-III associated with
      normal distortion product OEA suggest neurotoxicity in the brainstem pathways.
      The statistical significance reached only in the left ear may be due to small
      number of cases studied.

PMID- 24333889
TI  - The relationship between treatment of mental disorder and chronic tinnitus.
AB  - INTRODUCTION: Comorbidity of chronic tinnitus and mental disorders may result in
      more disability. OBJECTIVES: This research provides an evaluation about the
      effects of medically treated comorbid mental disorder on chronic tinnitus.
      MATERIALS AND METHODS: Fifty-five patients diagnosed with chronic tinnitus and
      mental disorders were randomly requited by producing a before-after design. They
      underwent three months of drug therapy for comorbid mental disorders by
      psychiatrists. Study instruments are Tinnitus Handicap Inventory, Tinnitus
      Questionnaire, Loudness Match Tinnitus, Hamilton Depression Rating Scale, Beck
      Anxiety Inventory, The Structured Clinical Interview and Symptom Check List -90.
      RESULTS: Three months medical treatment puts forward the argument that among
      mental disorders, anxiety and major depressive disorder demonstrate a significant
      reduction. Pearson Correlation coefficient ostensibly reveals that there is no
      significant relationship between mental disorders and tinnitus severity. The
      statistics lend support to profound effect of major depressive disorder as a key
      factor on tinnitus disability exacerbation. Medical treatment also touches on
      issue such as tinnitus severity, its disabling effects and TQ subscales that
      statistics shows significant trends in their reduction. CONCLUSION: Findings lay
      emphasis on tinnitus severity reduction and connection might be established
      between alleviated mental disorders comorbidity and the improvement of quality of
      life.

PMID- 24333890
TI  - Subjective tinnitus and its association with use of ear phones among students of
      the College of Medicine, University of Lagos, Nigeria.
AB  - INTRODUCTION: The ear can be damaged by excessive noise levels. Noise can arise
      from variety of occupational/recreational sources causing tinnitus, hearing loss
      and hyperacusis. The use of different types of ear phones for entertainment has
      become very common/fashionable among our youths. OBJECTIVES: This research aims
      to determine the prevalence of use of ear phones for entertainment and the
      prevalence of subjective tinnitus in students in an urban university setting; and
      the relationship between the two. METHODS: This is a descriptive, cross sectional
      study of students of the college of medicine, University of Lagos, Nigeria from
      January to April 2012. A total of 388 willing participants (203 males, 185
      females) were recruited by stratified random sampling from the 14 student hostel
      blocks. A self administered questionnaire was used. Data collected was analyzed
      using SPSS version 17.0.1. RESULTS AND CONCLUSION: The prevalence of earphone use
      among the students and subjective tinnitus was 95.6% and 20.6% respectively. More
      than 90% of the ear phone users had duration of ear phone use of duration of 3 to
      6 years.

PMID- 24333891
TI  - The effect of social support on quality of life for tinnitus sufferers.
AB  - OBJECTIVE: To examine the relationship between tinnitus severity, social support
      and three quality of life measures. BACKGROUND DATA: Research into other
      conditions shows that social support helps achieve positive outcomes and improved
      quality of life. For tinnitus, research suggests social support does not impact
      on quality of life outcomes. However, research has been limited and the measures
      used have mixed tinnitus severity, tinnitus handicap and social support into one
      measure. The aim of this research was to examine the relationship using separate
      measures. METHODS: One hundred fifty-four tinnitus sufferers (63.7% males, 36.3%
      females, Age M = 46.4, SD = 14.97) completed the assessment battery. Three
      sequential multiple regression analyses were conducted to test the hypothesis
      that social support moderates the effects of tinnitus severity on each of the
      dependent variables: tinnitus handicap, depression and general well-being.
      RESULTS: The severity of one's tinnitus significantly predicted tinnitus
      handicap, depression and general well-being, but social support did not moderate
      the relationship. Social support did have a direct relationship on level of
      depression and general well-being. CONCLUSION: Tinnitus handicaps appear to be
      unique but tinnitus sufferers do gain significant benefits from social support.

PMID- 24333892
TI  - Middle ear barotrauma after hyperbaric oxygen therapy - the role of insuflation
      maneuvers.
AB  - OBJECTIVE: To analyze the association of insuflation maneuvers status before
      hyperbaric oxygen therapy with middle ear barotrauma. MATERIALS AND METHODS:
      Fouty-one patients (82 ears) admitted to the Department of Hyperbaric Medicine
      from May 2011 to July 2012. Assessments occurred: before and after the first
      session, after sessions with symptoms. During the evaluations were performed:
      otoscopy with Valsalva and Toynbee maneuvers, video otoscopy and specific
      questionnaire. Middle ear barotrauma was graduated by the modified Edmond's
      scale. Tubal insuflation was classified in Good, Median and Bad according to
      combined results of Valsalva and Toynbee maneuvers. INCLUSION CRITERIA: patients
      evaluated by an otolaryngologist before and after the first session, with no
      history of ear disease, who agreed to participate in the research (convenience
      sample). RESULTS: Of the 82 ears included in the study, 32 (39%) had barotrauma
      after the first session. The rate of middle ear barotrauma according to tubal
      insuflation was: 17.9% (Good insuflation) 44.4% (Median insuflation) and 55.6%
      (Bad insuflation) (P = 0.013). CONCLUSION: Positive Valsalva and Toynbee
      maneuvers before the first session, alone or associated were protective factors
      for middle ear barotrauma by ear after the first session.

PMID- 24333893
TI  - Intratympanic corticotherapy and tinnitus control after sudden hearing loss.
AB  - INTRODUCTION: Sudden deafness is characterized by an abrupt onset, often
      idiopathic and tinnitus is present, and becomes the main complaint in up to 80%
      of patients. OBJECTIVE: To review carefully all studies of the past 10 years on
      sudden deafness and tinnitus and analyze the effectiveness of oral and
      intratympanic steroids for tinnitus control in eight patients with sudden
      deafness and severe disabling tinnitus. METHOD: An analytical prospective in
      which 64 patients after sudden deafness with tinnitus were monitored and 08 of
      these suffering with severe disabling tinnitus underwent hearing evaluation and
      application of the Tinnitus Handicap Inventory and Visual Analogue Scale before,
      during and after sudden deafness treated with oral and intratympanic steroids. It
      was made a systematic review of publications on the topic in the library of
      PubMed/MedLine, keywords: Sudden deafness and tinnitus. RESULTS: Eleven
      scientific studies were analyzed. Eight patients treated with intratympanic and
      oral corticosteroids were selected, just two patients showed improvement over the
      hearing but seven of them showed big improvement in their tinnitus, which was
      demonstrated by an improvement in the values of the degrees of severity of
      tinnitus. CONCLUSION: Patients with sudden deafness and severe disabling
      tinnitus, and underwent intratympanic and oral corticosteroids showed, in this
      study, significant reduction and/or remission of tinnitus.

PMID- 24333894
TI  - Auditory neuropathy spectrum: the importance of adequate diagnosis.
AB  - OBJECTIVE: To evaluate the prevalence of misdiagnosis of the hearing impaired
      children, in order to investigate the existence of Auditory Neuropathy Spectrum
      Disorder. METHODS: Analytical, prospective study conducted with 15 participants
      (30 ears) aged 10-12 years, with bilateral sensorineural hearing loss, attending
      a Hearing Rehabilitation Center, accompanied by a multidisciplinary team with
      otolaryngologist, audiologist, psychologist, teacher and social worker. The
      participants underwent ENT examination and audiological assessment: tympanometry,
      acoustic reflexes, otoacoustic emissions test and Auditory Evoked response.
      RESULTS: From the total sample (30 ears), 8 ears (26.7%) presented absent
      responses in the Auditory Evoked response with the presence of cochlear
      microphonism. Within the selected eight ears, six (75%) showed presence of
      otoacoustic emissions test in isolated frequencies and two (25%) ears had
      otoacoustic emissions test even in the presence of the isolated frequencies. It
      was found that 26.7% of the ears tested presented results that are compatible
      with Auditory Neuropathy Spectrum Disorder. CONCLUSION: The results of this study
      have identified characteristics related to ANSD in 26.7% of ears tested, 6
      participants with age over 10 years old, showing that misdiagnosis in hearing
      loss patients is still very frequent.

PMID- 24333895
TI  - Cochlear implant in the treatment of incapacitating unilateral tinnitus: case
      report.
AB  - Several studies have shown that cochlear implants may reduce or even eliminate
      tinnitus in patients with bilateral profound hearing loss. However, there are not
      consistent references regarding ipsilateral tinnitus compared to unilateral
      profound hearing loss. The aim of this paper is to describe audiological results
      of a patient with asymmetrical hearing loss with incapacitating ipsilateral
      tinnitus in the ear subjected to cochlear implant surgery. Audiological exams and
      responses to perception protocols for tinnitus before and after surgery were
      analyzed. The tests showed improvements in the hearing threshold on the side with
      the implant, improvements in speech perception and a significant reduction in
      tinnitus perception, which consequently led to an improvement in the patient's
      quality of life. 

PMID- 24333897
TI  - Planococcus maritimus VITP21 synthesizes (2-acetamido-2-deoxy-alpha-d
      glucopyranosyl)-(1->2)-beta-d-fructofuranose under osmotic stress: a novel
      protein stabilizing sugar osmolyte.
AB  - A halotolerant bacterium, Planococcus maritimus VITP21 isolated from a saltern
      region in Kumta along the Arabian Sea Coast of India was found to have increased
      cellular levels of sugars (up to 2.3-fold) under osmotic stress when grown in
      minimal medium with glucose as the sole carbon and energy source supplemented
      with 10% w/v NaCl. The major sugar osmolyte which increased with the
      concentration of NaCl in the growth medium was purified and characterized using
      various nuclear magnetic resonance spectroscopy techniques. The sugar was found
      to be similar to sucrose but with the C-2 hydroxyl group of the glucose ring
      substituted with acetamido group, which is not previously reported for its
      natural synthesis by any other organism. This novel sugar, (2-acetamido-2-deoxy
      alpha-d-glucopyranosyl)-(1->2)-beta-d-fructofuranose, exhibited stabilizing
      effect on a model protein alpha-amylase by increasing the apparent midpoint
      transition, onset temperature of denaturation, and free energy of thermal
      unfolding. 

PMID- 24333896
TI  - C. elegans in high-throughput drug discovery.
AB  - Caenorhabditis elegans has been proven to be a useful model organism for
      investigating molecular and cellular aspects of numerous human diseases. More
      recently, investigators have explored the use of this organism as a tool for drug
      discovery. Although earlier drug screens were labor-intensive and low in
      throughput, recent advances in high-throughput liquid workflows, imaging
      platforms and data analysis software have made C. elegans a viable option for
      automated high-throughput drug screens. This review will outline the evolution of
      C. elegans-based drug screening, discuss the inherent challenges of using C.
      elegans, and highlight recent technological advances that have paved the way for
      future drug screens. 

PMID- 24333898
TI  - Synthesis, characterization, and comparative analysis of amylose-guest complexes
      prepared by microwave irradiation.
AB  - The preparation and characterization of amylose-small molecule complexes is a
      heavily researched area. There are few reports, however, that compare
      complexation efficiencies across a matrix of different amylose hosts and guests.
      We present herein a detailed account of using microwave irradiation to prepare
      amylose-small molecule complexes in water. Microwave heating reduced the time
      required to prepare these amylose complexes from hours to minutes. We
      characterized not only the quantity of complex for each amylose-guest pairing but
      also the loading of small molecule guest in that complex. Amylose-1-naphthol
      complexes were found to have the highest loading density compared with other
      hydrophobic guests studied; in the case of 1-naphthol, there was a linear
      dependence of guest loading on amylose molecular weight. In addition, complexes
      featuring 1-naphthol were the most ordered as judged by powder X-ray diffraction
      (XRD) and differential scanning calorimetry. Further, powder XRD analysis of the
      microwave-prepared complexes revealed that many contained mixtures of V-form
      (single helix) and B-form (double helical) amylose. Lastly, untreated Hylon VII
      complexed the widest variety of small molecules with the overall greatest
      efficiency. 

PMID- 24333899
TI  - Combined approaches to flexible fitting and assessment in virus capsids
      undergoing conformational change.
AB  - Fitting of atomic components into electron cryo-microscopy (cryoEM) density maps
      is routinely used to understand the structure and function of macromolecular
      machines. Many fitting methods have been developed, but a standard protocol for
      successful fitting and assessment of fitted models has yet to be agreed upon
      among the experts in the field. Here, we created and tested a protocol that
      highlights important issues related to homology modelling, density map
      segmentation, rigid and flexible fitting, as well as the assessment of fits. As
      part of it, we use two different flexible fitting methods (Flex-EM and iMODfit)
      and demonstrate how combining the analysis of multiple fits and model assessment
      could result in an improved model. The protocol is applied to the case of the
      mature and empty capsids of Coxsackievirus A7 (CAV7) by flexibly fitting homology
      models into the corresponding cryoEM density maps at 8.2 and 6.1A resolution. As
      a result, and due to the improved homology models (derived from recently solved
      crystal structures of a close homolog - EV71 capsid - in mature and empty forms),
      the final models present an improvement over previously published models. In
      close agreement with the capsid expansion observed in the EV71 structures, the
      new CAV7 models reveal that the expansion is accompanied by ~5 degrees 
      counterclockwise rotation of the asymmetric unit, predominantly contributed by
      the capsid protein VP1. The protocol could be applied not only to viral capsids
      but also to many other complexes characterised by a combination of atomic
      structure modelling and cryoEM density fitting. 

PMID- 24333900
TI  - Investigating the role of cholesterol in the formation of non-ionic surfactant
      based bilayer vesicles: thermal analysis and molecular dynamics.
AB  - The aim of this research was to investigate the molecular interactions occurring
      in the formulation of non-ionic surfactant based vesicles composed monopalmitoyl
      glycerol (MPG), cholesterol (Chol) and dicetyl phosphate (DCP). In the
      formulation of these vesicles, the thermodynamic attributes and surfactant
      interactions based on molecular dynamics, Langmuir monolayer studies,
      differential scanning calorimetry (DSC), hot stage microscopy and
      thermogravimetric analysis (TGA) were investigated. Initially the melting points
      of the components individually, and combined at a 5:4:1 MPG:Chol:DCP weight
      ratio, were investigated; the results show that lower (90  degrees C) than
      previously reported (120-140  degrees C) temperatures could be adopted to produce
      molten surfactants for the production of niosomes. This was advantageous for
      surfactant stability; whilst TGA studies show that the individual components were
      stable to above 200  degrees C, the 5:4:1 MPG:Chol:DCP mixture show ~2%
      surfactant degradation at 140  degrees C, compared to 0.01% was measured at 90 
      degrees C. Niosomes formed at this lower temperature offered comparable
      characteristics to vesicles prepared using higher temperatures commonly reported
      in literature. In the formation of niosome vesicles, cholesterol also played a
      key role. Langmuir monolayer studies demonstrated that intercalation of
      cholesterol in the monolayer did not occur in the MPG:Chol:DCP (5:4:1 weight
      ratio) mixture. This suggests cholesterol may support bilayer assembly, with
      molecular simulation studies also demonstrating that vesicles cannot be built
      without the addition of cholesterol, with higher concentrations of cholesterol
      (5:4:1 vs 5:2:1, MPG:Chol:DCP) decreasing the time required for niosome assembly.

PMID- 24333901
TI  - Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms.
AB  - A drug delivery platform comprising a biocompatible, bioresponsive hydrogel and
      possessing a covalently tethered peptide-drug conjugate was engineered to achieve
      stasis, via a closed control loop, of the external biochemical activity of the
      actuating protease. The delivery platform contains a peptide-drug conjugate
      covalently tethered to the hydrogel matrix, which in the presence of the
      appropriate protease, was cleaved and the drug released into the bathing
      environment. This platform was developed and investigated in silico using a
      finite element modeling (FEM) approach. Firstly, the primary governing phenomena
      guiding drug release profiles were investigated, and it was confirmed that under
      transport-limited conditions, the diffusion of the enzyme within the hydrogel and
      the coupled enzyme kinetics accurately model the system and are in agreement with
      published results. Secondly, the FEM model was used to investigate the release of
      a competitive protease inhibitor, MAG283, via cleavage of Acetyl-Pro-Leu-Gly|Leu
      MAG-283 by MMP9 in order to achieve targeted homeostasis of MMP-9 activity, such
      as in the pathophysiology of chronic wounds, via closed-loop feedback control.
      The key engineering parameters for the delivery device are the radii of the
      hydrogel microspheres and the concentration of the peptide-inhibitor conjugate.
      Homeostatic drug delivery, where the focus turns away from the drug release rate
      and turns toward achieving targeted control of biochemical activity within a
      biochemical pathway, is an emerging approach in drug delivery methodologies for
      which the potential has not yet been fully realized. 

PMID- 24333902
TI  - In vitro release testing of matrices based on starch-methyl methacrylate
      copolymers: effect of tablet crushing force, dissolution medium pH and stirring
      rate.
AB  - Direct-compressed matrix tablets were obtained from a variety of potato starch
      methyl methacrylate copolymers(1) as sustained-release agents, using anhydrous
      theophylline as a model drug. The aim of this work was to investigate the
      influence of the copolymer type, the tablet crushing force and dissolution
      variables such as the pH of the dissolution medium and the agitation intensity on
      the in vitro drug release behaviour of such matrices. Commercial sustained
      release theophylline products (Theo-Dur((r)) 100mg, Theolair((r)) 175 mg) were
      used as standards. Test formulations were compacted into tablets at three
      different crushing force ranges (70-80, 90-100 and 110-120 N) to examine the
      effect of this factor on the porous network and drug release kinetics. In vitro
      release experiments were conducted in a pH-changing medium (1.2-7.5) with basket
      rotation speeds in the range 25-100 r.p.m. to simulate the physiological
      conditions of the gastrointestinal tract. The release rate of theophylline was
      practically not affected by pH in the case of Theo-Dur((r)) and HSMMA matrices.
      In contrast, Theolair((r)) and CSMMA tablets demonstrated a biphasic drug release
      pattern, which appeared to be sensitive to the pH of the dissolution medium. An
      increase in the crushing force of the copolymer matrices was accompanied by a
      reduction of the matrix porosity, although the porous network depends markedly on
      the type of copolymer, having a strong influence on the drug release kinetics.
      Mathematical modelling of release data shows a Fickian diffusion or anomalous
      transport mechanism. Based on the similarity factor f2, FD-HSMMA, OD-CSMMA and FD
      CSMMA at 90-100 N were selected for agitation studies. In general, all
      formulations showed an agitation speed-dependent release, with Theo-Dur((r)) and
      FD-CSMMA matrices being the less susceptible to this factor.

PMID- 24333904
TI  - Acrylic polymer-grafted polypropylene sutures for covalent immobilization or
      reversible adsorption of vancomycin.
AB  - Glycidyl methacrylate (GMA) and acrylic acid (AAc) were separately grafted onto
      polypropylene (PP) monofilament sutures by means of pre-irradiation using a
      (60)Co gamma-source, with the purpose of loading vancomycin via (i) covalent
      immobilization through the glycidyl groups of GMA and (ii) ionic interaction with
      AAc moieties. The effect of absorbed radiation dose, monomer concentration,
      temperature and reaction time on the grafting degree was evaluated in detail. GMA
      grafting ranged from 25% to 800% while the grafting yield of AAc onto PP could be
      tuned between 9% and 454%, at doses from 5 to 50 kGy and a dose rate 13.7 kGy/h.
      Grafting of GMA or AAc decreased the decomposition temperature and made the
      sutures swellable to a certain extent. GMA grafting led to a continuous, smooth
      and thick coating, which was suitable for immobilization of up to 1.9 MUg
      vancomycin per gram. The immobilized vancomycin enabled a reduction in the
      Staphylococcus aureus CFU adhered to the suture surface. On the other hand, dried
      AAc-functionalized sutures exhibited a rough and cracked surface which was
      responsible for a minor increase in the coefficient of friction. PP-g-AAc sutures
      exhibited pH-dependent swelling and remarkably high capability to host vancomycin
      (up to 109.9 mg/g), particularly those with an intermediate degree of grafting.
      Some AAc-functionalized sutures were shown able to inhibit bacterial growth after
      successive challenges with fresh lawns. Therefore, tuning the yield of grafting
      of GMA or AAc may enable the preparation of drug-suture combination products that
      retain or release, respectively, antimicrobial agents.

PMID- 24333905
TI  - Redispersible fast dissolving nanocomposite microparticles of poorly water
      soluble drugs.
AB  - Enhanced recovery/dissolution of two wet media-milled, poorly water-soluble
      drugs, Griseofulvin (GF) and Azodicarbonamide (AZD), incorporated into
      nanocomposite microparticles (NCMPs) via fluidized bed drying (FBD) and spray
      drying (SD) was investigated. The effects of drying method, drug loading, drug
      aqueous solubility/wettability as well as synergistic stabilization of the milled
      suspensions on nanoparticle recovery/dissolution were examined. Drug nanoparticle
      recovery from FBD and SD produced NCMPs having high drug loadings was evaluated
      upon gentle redispersion via optical microscopy and laser diffraction. During wet
      milling, hydroxypropyl cellulose (HPC) alone stabilized more wettable drug (AZD)
      nanoparticles with slight aggregation, but could not prevent aggregation of the
      GF nanoparticles. In contrast, well-dispersed, stable nanosuspensions of both
      drugs were produced when sodium dodecyl sulfate (SDS) and HPC were combined. The
      FBD and SD NCMPs without SDS exhibited incomplete nanoparticle recovery, causing
      slower dissolution for GF, but not for AZD, likely due to higher aqueous
      solubility/wettability of AZD. For high active loaded NCMPs (FBD ~50 wt%, SD ~80
      wt%) of either drug, HPC-SDS together owing to their synergistic stabilization
      led to fast redispersibility/dissolution, corroborated via optical microscopy and
      particle sizing. These positive attributes can help development of smaller, high
      drug-loaded dosage forms having enhanced bioavailability and better patient
      compliance.

PMID- 24333903
TI  - Microparticles produced by the hydrogel template method for sustained drug
      delivery.
AB  - Polymeric microparticles have been used widely for sustained drug delivery.
      Current methods of microparticle production can be improved by making homogeneous
      particles in size and shape, increasing the drug loading, and controlling the
      initial burst release. In the current study, the hydrogel template method was
      used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and
      to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA)
      was used to make hydrogel templates. The parameters examined include PVA
      molecular weight, type of PLGA (as characterized by lactide content, inherent
      viscosity), polymer concentration, drug concentration and composition of solvent
      system. Three model compounds studied were risperidone, methylprednisolone
      acetate and paclitaxel. The ability of the hydrogel template method to produce
      microparticles with good conformity to template was dependent on molecular weight
      of PVA and viscosity of the PLGA solution. Drug loading and encapsulation
      efficiency were found to be influenced by PLGA lactide content, polymer
      concentration and composition of the solvent system. The drug loading and
      encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for
      methylprednisolone acetate, and 32.2% and 92% for paclitaxel, respectively. For
      all three drugs, release was sustained for weeks, and the in vitro release
      profile of risperidone was comparable to that of microparticles prepared using
      the conventional emulsion method. The hydrogel template method provides a new
      approach of manipulating microparticles. 

PMID- 24333906
TI  - Development of a pressure-sensitive glyceryl tristearate capsule filled with a
      drug-containing hydrogel.
AB  - The purpose of this work was to develop a new pressure-sensitive dosage form that
      breaks and releases its content in a fasted stomach at the predominant pressure
      at the pylorus. The content of the dosage form should be liquid so that the
      active pharmaceutical ingredient quickly reaches maximum absorption in the upper
      small intestine. For this purpose glyceryl tristearate capsules were developed,
      consisting of an extremely brittle shell, with a crushing behavior that can be
      controlled by modification of the shell thickness. The capsules were filled with
      a hydroxyethyl cellulose gel containing paracetamol. Dissolution testing using
      USP apparatus 2, performed for simulating the resting time in the stomach, did
      not show any release. Studies using a texture analyser showed a correlation
      between the glyceryl tristearate filling volume and the necessary force to break
      the capsule. Physiological conditions in dissolution testing, such as movement,
      pressure and discontinuous medium contact, were set in a stress test device and
      showed that the dosage forms did not break and release its pharmaceutical
      ingredient until a pressure of 300 mbar was applied which served as a threshold
      limit for physiological pressure occurring during gastric emptying of large
      solids.

PMID- 24333907
TI  - A pharmacokinetic study on a novel anti-HBV agent imidol hydrochloride in rats.
AB  - Imidol hydrochloride is a novel agent for the treatment of hepatitis B virus
      (HBV) infection, which is currently being evaluated in a phase II trial. This
      study investigated the absorption, excretion and tissue distribution of imidol
      after an oral dose in rats. The pharmacokinetic parameters were determined for
      both intravenous and oral dosing. A simple and sensitive UPLC-MS-MS method was
      employed to determine the imidol levels in rat biological samples. It was applied
      for the analysis of imidol in plasma, urine, feces, bile and various tissue
      samples. Imidol was found to have a moderate half-life (~4 h), a relatively large
      apparent distribution volume and rapid clearance after an IV dose and oral doses
      up to 70 mg kg(-1). Dose-dependent linear relationships of AUC0-t and Cmax for
      imidol was found in the range of 10-70 mg kg(-1) after oral administration to
      rats. However, the oral bioavailability was low (17.6%). Most of the drug was
      metabolized and only 20% of the parent drug was excreted. Imidol excreted mainly
      in feces. The tissue distribution results show that imidol was quickly dispersed
      to various tissues following an oral dose. Relatively high concentration was
      found in liver, which is beneficial to the intended indication. Very low levels
      of imidol were found in brain and testes, indicating that it was difficult for
      imidol to cross the blood-brain barrier.

PMID- 24333908
TI  - Formation and dissolution of chitosan/pyrophosphate nanoparticles: is the ionic
      crosslinking of chitosan reversible?
AB  - Ionically crosslinked chitosan particles with submicron dimensions attract
      widespread interest as materials for controlled release. To this end, we have
      examined the formation and dissolution of nanoparticles prepared by crosslinking
      chitosan with pyrophosphate (PPi). The formation of these particles required a
      critical PPi concentration (which increased with the chitosan concentration), and
      their z-average hydrodynamic diameters could be predictably tuned from roughly 60
      to 220 nm by varying the concentration of the parent chitosan solutions. Unlike
      the nanoparticles crosslinked with the commonly used tripolyphosphate (TPP),
      which coagulated and precipitated when TPP was in excess, the chitosan/PPi
      nanoparticles remained colloidally stable even at high PPi concentrations.
      Moreover, the analysis of their dissolution revealed hysteresis in the particle
      formation/dissolution cycle, where portions of the crosslinked chitosan/PPi
      complexes remained stably intact at PPi concentrations below those required for
      their formation. This irreversible behavior was surmised to reflect the
      cooperativity of chitosan/PPi binding and was qualitatively modeled using the
      Bragg-Williams theory.

PMID- 24333909
TI  - Characterization and biodistribution in vivo of quercetin-loaded cationic
      nanostructured lipid carriers.
AB  - Nanobiotechnology has been recently viewed as a promising strategy to improve
      therapy efficacy by promoting the accumulation of hydrophobic bioactive compounds
      in tissues. The aim of present study was to formulate a novel quercetin-loaded
      cationic nanostructured lipid carriers (QR-CNLC) and to evaluate its
      biodistribution in vivo after oral administration. QR-CNLC were prepared by
      emulsifying at high temperature and subsequent solidifying at low temperature
      using various functional ingredients, and its characteristics, including physical
      index, release profile in vitro, and tissue distribution in vivo, were
      investigated. The results demonstrated that QR-CNLC exhibited an average particle
      size 126.6 nm, a zeta potential of 40.5 mV and 89.3% entrapment efficiency. QR
      CNLC performed slower release compared with quercetin solution in vitro. QR-CNLC
      showed higher AUC (area under tissue concentration-time curve) value and higher
      Cmax value in lung, liver and kidney compared with control group. The value of
      relative intake rate (re) for lung, liver and kidney was 1.57, 1.51 and 1.68,
      respectively, which revealed that quercetin can be significantly accumulated in
      lung, kidney and liver after oral administration of QR-CNLC compared with
      quercetin suspension. In conclusion, cationic nanostructured lipid carriers may
      be an attractive nanocarrier system for oral delivery of hydrophobic functional
      components.

PMID- 24333910
TI  - Semi-interpenetrating network of acrylamide-grafted-sodium alginate microspheres
      for controlled release of diclofenac sodium, preparation and characterization.
AB  - The semi-interpenetrating networks (semi-IPNs) of acrylamide grafted sodium
      alginate (AAm-g-NaAlg) microspheres (MPs) were prepared by emulsion-crosslinking
      method using glutaraldehyde (GA) as a crosslinking agent. The grafting of
      acrylamide onto sodium alginate was prepared by free-radical graft polymerization
      using ceric ammonium nitrate (CAN) as initiator at three acrylamide
      concentrations with monomer to polymer ratio of 1:1, 2:1 and 3:1, respectively.
      The grafting efficiency was found to be 91%. The produced MPs are almost
      spherical in nature with smooth surfaces. Diclofenac sodium (DS), an anti
      inflammatory drug was successfully encapsulated into the MPs. The encapsulation
      efficiency was found to vary between 83% and 95%. The MPs were characterized by
      differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and
      Fourier transform infrared (FTIR) spectroscopy. The diffusion coefficient (D) was
      dependent upon the amount of crosslinking agent (GA) and amount of grafting ratio
      in the matrix. The rate of release was found to be dependent on the amount of GA,
      AAm:NaAlg grafting ratio and % drug loading in the MPs. The release data have
      been fitted to an empirical equation to investigate the diffusional exponent (n),
      which indicated that the release mechanism from MPs follows the super Case II
      transport. 

PMID- 24333911
TI  - False positives in Biolog EcoPlatesTM and MT2 MicroPlatesTM caused by calcium.
AB  - Biolog MicroPlates(TM) (e.g. EcoPlate(TM), MT2 MicroPlate(TM), GN MicroPlate(TM))
      are useful tools for characterizing microbial communities, providing community
      level physiological profiles to terrestrial and aquatic ecologists. The more
      recently designed Biolog EcoPlates have been used frequently in aquatic ecology
      with success. This study, however, reveals one major problem when using EcoPlates
      to evaluate samples within an estuarine or seawater matrix. At concentrations
      greater than 100 parts per million, the cation calcium begins to interfere with
      the microplate chemistry, causing false positive readings. Experiments, in which
      multiple treatments of natural and artificial seawater were tested, as well as
      calcium-addition experiments, demonstrate that calcium inhibits complete
      dissolution of the minimal growth medium in wells. Future studies involving
      Biolog EcoPlates and MicroPlates should take this effect into account, and the
      dilution of samples is strongly recommended to diminish the "calcium effect." 

PMID- 24333912
TI  - Development and evaluation of a TaqMan duplex real-time PCR quantification method
      for reliable enumeration of Candidatus Microthrix.
AB  - Candidatus Microtrhix parvicella is one of the most common filamentous bacteria
      reported to be involved in bulking and foaming problems in activated sludge
      plants worldwide. In order to detect and quantify both M. parvicella and
      Microthrix calida by quantitative PCR (qPCR), primers targeting 16S rDNA genes
      were designed. The qPCR reaction was optimized by using the TaqMan technology and
      an internal positive control was included to ensure the absence of PCR
      inhibitors. A total of 29 samples originating from different wastewater treatment
      plants were analyzed and the results were compared by using conventional
      microscopy, fluorescent in situ hybridization and an existing SYBR Green-based
      assay. Our assay showed a 100% specificity for both M. parvicella and M. calida,
      a sensitivity of 2.93*10(9) to 29 copy numbers/reaction, an amplification
      efficiency of 93% and no PCR inhibition. By performing a spiking experiment
      including different Microthrix concentrations, recovery rates ranging from 65 to
      98% were obtained. A positive correlation with the SYBR Green assay (R(2)=0.85)
      was found and most of the samples were in accordance with the microscopical
      observation. In comparison with SYBR Green assay, the probe-based TaqMan assay
      had a much lower detection limit. Compared with microscopy, some samples had a
      lower or higher enumeration when using qPCR. In conclusion, a qPCR method is
      forwarded here that could be useful as an early warning tool for fast and
      reliable detection of Microthrix in for instance sludge bulking events. 

PMID- 24333913
TI  - Shortened cortical silent period in adductor spasmodic dysphonia: evidence for
      widespread cortical excitability.
AB  - The purpose of this study was to compare cortical inhibition in the hand region
      of the primary motor cortex between subjects with focal hand dystonia (FHD),
      adductor spasmodic dysphonia (AdSD), and healthy controls. Data from 28 subjects
      were analyzed (FHD n=11, 53.25 +/- 8.74 y; AdSD: n=8, 56.38 +/- 7.5 y; and
      healthy controls: n=941.67 +/- 10.85 y). All subjects received single pulse TMS
      to the left motor cortex to measure cortical silent period (CSP) in the right
      first dorsal interosseus (FDI) muscle. Duration of the CSP was measured and
      compared across groups. A one-way ANCOVA with age as a covariate revealed a
      significant group effect (p<0.001). Post hoc analysis revealed significantly
      longer CSP duration in the healthy group vs. AdSD group (p<0.001) and FHD group
      (p<0.001). These results suggest impaired intracortical inhibition is a
      neurophysiologic characteristic of FHD and AdSD. In addition, the shortened CSP
      in AdSD provides evidence to support a widespread decrease in cortical inhibition
      in areas of the motor cortex that represent an asymptomatic region of the body.
      These findings may inform future investigations of differential diagnosis as well
      as alternative treatments for focal dystonias.

PMID- 24333914
TI  - Insulin-like growth factor 1 induces the transcription of Gap43 and Ntn1 during
      hair cell protection in the neonatal murine cochlea.
AB  - We previously reported that insulin-like growth factor 1 (IGF-1) protects
      cochlear hair cells against aminoglycosides through activation of the PI3K/Akt
      and MEK/ERK pathways in supporting cells. In this study, we found that IGF-1 up
      regulated the expression levels of Gap43 and Ntn1 as measured using cDNA
      microarray analysis and qRT-PCR. Using inhibitors of the PI3K/Akt and MEK/ERK
      pathways, we reveal that both pathways are involved in the up-regulation of Gap43
      and Ntn1 expression. Moreover the time window of Gap43 and Ntn1 transcription was
      limited to within 12h after IGF-1 treatment, indicating that downstream gene
      expression was tightly controlled by IGF-1. 

PMID- 24333915
TI  - A probabilistic damage model based on direct 3-D correlation of strain to damage
      formation following fatigue loading of rat femora.
AB  - Microdamage accumulates in bone due to repetitive or excessive mechanical
      loading, and accumulation of damage can lead to an increase in fracture
      susceptibility. Understanding the stress or strain criterion for damage formation
      would allow improved predictive modeling to better assess experimental results or
      evaluate training regimens. Finite element models coupled with three-dimensional
      measurements of damage were used to directly correlate damage formation to the
      local strain state in whole rat femora subjected to three-point bending fatigue.
      Images of accumulated damage from contrast-enhanced micro-CT were overlaid onto
      the calculated strain result to determine the strain associated with damage. Most
      microdamage accumulated in areas where the first principal strain exceeded 0.5%,
      but damage also occurred at lower strains when applied over sufficiently large
      volumes. As such, a single threshold strain was not a good predictor of damage.
      In order to capture the apparently stochastic nature of damage formation, a
      Weibull statistical model was applied. The model provided a good fit to the data,
      and a fit based on a subset of the data was able to predict the results in the
      remaining samples with an RMS error of 17%. These results demonstrate that damage
      formation is dependent on principal strain, but has a random component that is
      likely due to the presence of pores or flaws smaller than the resolution of the
      model that act as stress concentrations in bone. 

PMID- 24333916
TI  - Self-assemblies of tricationic porphyrin on inorganic polyphosphate.
AB  - Self-assemblies formed by the new synthesized tricationic porphyrin derivative
      (TMPyP(3+)) on the polyanionic inorganic polyphosphate (PPS) in aqueous solution
      were studied using different spectroscopic techniques and DFT calculation method.
      From the fluorescence quenching of the bound TMPyP(3+) molecules and their Raman
      spectra we conclude that porphyrin chromophores form the stable pi-pi stacking
      assemblies onto PPS polyanions. The transformation of the Soret band in
      absorption spectra at different PPS/TMPyP(3+)concentration ratios evidences that
      the assemblies are mixtures of J- and H-aggregates. Molecular modeling performed
      shows that the flexibility of PPS strand allows a realization of spiral or "face
      to-face" one-dimensional structures formed by porphyrin molecules arranged in
      parallel and antiparallel modes. The peculiarity of PPS structure allows a
      formation of two porphyrin stacks on opposite sides of polymer strands that
      result in the appearance of higher-order aggregates. Their size was estimated
      from the light scattering data. Distinctions between TMPyP(3+) and TMPyP4
      aggregation on PPS template are discussed. 

PMID- 24333917
TI  - Length-dependent conformational transitions of polyglutamine repeats as molecular
      origin of fibril initiation.
AB  - Polyglutamine (polyQ) sequences are found in a variety of proteins with normal
      function. However, their repeat expansion is associated with a number of
      neurodegenerative diseases, also called polyQ diseases. The length of the polyQ
      sequence, varying in the number of consecutive glutamines among different
      diseases, is critical for inducing fibril formation. We performed a systematic
      spectroscopic study to analyze the conformation of polyQ model peptides in
      dependence of the glutamine sequence lengths (K2QnK2 with n=10, 20, 30).
      Complementary FTIR- and CD-spectra were measured in a wide concentration range
      and repeated heating and cooling cycles revealed the thermal stability of formed
      beta-sheets. The shortest glutamine sequence K2Q10K2 shows solely random
      structure for concentrations up to 10 mg/ml. By increasing the peptide length to
      K2Q20K2, a significant fraction of beta-sheet is observed even at low
      concentrations of 0.01 mg/ml. The higher the concentration, the more the
      structural composition is dominated by the intermolecular beta-sheet. The
      formation of highly thermostable beta-sheet is much more pronounced in K2Q30K2.
      K2Q30K2 precipitates at a concentration of 0.3 mg/ml. Our spectroscopic study
      shows that the aggregation tendency is enhanced with increased glutamine repeat
      expansion and that the concentration plays another critical factor in the beta
      sheet formation.

PMID- 24333918
TI  - Differential susceptibility to the Withering Syndrome agent and renal coccidia in
      juvenile Haliotis rufescens, Haliotis discus hannai and the interspecific hybrid.
AB  - Withering Syndrome (WS) is a pathogenic chronic disease caused by the
      intracellular rickettsial-like bacterium "Candidatus Xenohaliotis californiensis"
      (WS-RLOs), which affects many abalone species. The renal coccidium (Margolisiella
      haliotis) has often been observed concurrent with WS infection. The red abalone
      Haliotis rufescens is a very susceptible species to WS and is also infected by
      the coccidium M. haliotis. In contrast, the Japanese abalone Haliotis discus
      hannai is not infected by these parasites. Interspecific hybridization is a
      method for improving important traits in animal husbandry. The objective of this
      study was to determine susceptibility to WS-RLO and M. haliotis infection in the
      hybrid generated from a cross between red and Japanese abalones. Juveniles from
      both species and the interspecific hybrid were challenged by exposure to effluent
      from red abalone adults infected with both parasites. The animals were analyzed
      by histology at 130days post-challenge. A 33% prevalence WS-RLOs was observed in
      the red abalone H. rufescens, whereas a 20% prevalence was observed in the
      hybrid. Infections were graded on a scale of 0-3. Of these red abalones infected,
      53% presented grade 1 infection intensity, 10% had grade 2 infections, and 50%
      had grade 3 infections. However, the hybrids only presented intensities at the
      extremes of the scale; of those infected 33% showed grade 1 infections and 66%
      had grade 3 infections. The coccidium prevalence was 7% in red abalone
      individuals and 13% in the hybrid abalone. In contrast, the Japanese abalone did
      not present infections with either parasite. As with the prevalence, the
      infection intensities for the coccidium were higher in the hybrid abalone; of
      those infected 25% had grade 2 infections, and 75% had grade 3 infections, but
      the red abalone presented only grade 2 infection intensities. Therefore, the
      hybrid did not inherited non-susceptibility or resistance characteristics of the
      parental H. discus hannai and possessed biological conditions that could foster
      development of both parasites. Development of a culture based on this hybrid
      abalone should consider its susceptibility to infection by coccidian, WS-RLOs and
      the potential for developing the WS disease. 

PMID- 24333920
TI  - Biogeography in deep time - What do phylogenetics, geology, and paleoclimate tell
      us about early platyrrhine evolution?
AB  - Molecular data have converged on a consensus about the genus-level phylogeny of
      extant platyrrhine monkeys, but for most extinct taxa and certainly for those
      older than the Pleistocene we must rely upon morphological evidence from fossils.
      This raises the question as to how well anatomical data mirror molecular
      phylogenies and how best to deal with discrepancies between the molecular and
      morphological data as we seek to extend our phylogenies to the placement of
      fossil taxa. Here I present parsimony-based phylogenetic analyses of extant and
      fossil platyrrhines based on an anatomical dataset of 399 dental characters and
      osteological features of the cranium and postcranium. I sample 16 extant taxa
      (one from each platyrrhine genus) and 20 extinct taxa of platyrrhines. The tree
      structure is constrained with a "molecular scaffold" of extant species as
      implemented in maximum parsimony using PAUP with the molecular-based 'backbone'
      approach. The data set encompasses most of the known extinct species of
      platyrrhines, ranging in age from latest Oligocene (~26 Ma) to the Recent. The
      tree is rooted with extant catarrhines, and Late Eocene and Early Oligocene
      African anthropoids. Among the more interesting patterns to emerge are: (1) known
      early platyrrhines from the Late Oligocene through Early Miocene (26-16.5Ma)
      represent only stem platyrrhine taxa; (2) representatives of the three living
      platyrrhine families first occur between 15.7 Ma and 13.5 Ma; and (3) recently
      extinct primates from the Greater Antilles (Cuba, Jamaica, Hispaniola) are sister
      to the clade of extant platyrrhines and may have diverged in the Early Miocene.
      It is probable that the crown platyrrhine clade did not originate before about 20
      24 Ma, a conclusion consistent with the phylogenetic analysis of fossil taxa
      presented here and with recent molecular clock estimates. The following
      biogeographic scenario is consistent with the phylogenetic findings and climatic
      and geologic evidence: Tropical South America has been a center for platyrrhine
      diversification since platyrrhines arrived on the continent in the middle
      Cenozoic. Platyrrhines dispersed from tropical South America to Patagonia at ~25
      24 Ma via a "Parana Portal" through eastern South America across a retreating
      Paranense Sea. Phylogenetic bracketing suggests Antillean primates arrived via a
      sweepstakes route or island chain from northern South America in the Early
      Miocene, not via a proposed land bridge or island chain (GAARlandia) in the Early
      Oligocene (~34 Ma). Patagonian and Antillean platyrrhines went extinct without
      leaving living descendants, the former at the end of the Early Miocene and the
      latter within the past six thousand years. Molecular evidence suggests crown
      platyrrhines arrived in Central America by crossing an intermittent connection
      through the Isthmus of Panama at or after 3.5Ma. Any more ancient Central
      American primates, should they be discovered, are unlikely to have given rise to
      the extant Central American taxa in situ.

PMID- 24333921
TI  - ECG screening of athletes improves diagnostic yield--next step: does it save
      lives?

PMID- 24333919
TI  - Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening
      electrophilic dermal sensitizers.
AB  - Chemical allergens bind directly, or after metabolic or abiotic activation, to
      endogenous proteins to become allergenic. Assessment of this initial binding has
      been suggested as a target for development of assays to screen chemicals for
      their allergenic potential. Recently we reported a nitrobenzenethiol (NBT) based
      method for screening thiol reactive skin sensitizers, however, amine selective
      sensitizers are not detected by this assay. In the present study we describe an
      amine (pyridoxylamine (PDA)) based kinetic assay to complement the NBT assay for
      identification of amine-selective and non-selective skin sensitizers. UV-Vis
      spectrophotometry and fluorescence were used to measure PDA reactivity for 57
      chemicals including anhydrides, aldehydes, and quinones where reaction rates
      ranged from 116 to 6.2 * 10(-6) M(-1) s(-1) for extreme to weak sensitizers,
      respectively. No reactivity towards PDA was observed with the thiol-selective
      sensitizers, non-sensitizers and prohaptens. The PDA rate constants correlated
      significantly with their respective murine local lymph node assay (LLNA)
      threshold EC3 values (R(2) = 0.76). The use of PDA serves as a simple,
      inexpensive amine based method that shows promise as a preliminary screening tool
      for electrophilic, amine-selective skin sensitizers.

PMID- 24333922
TI  - Bilateral cardiac sympathetic denervation: the last resort?

PMID- 24333923
TI  - Successful simultaneous unipolar radiofrequency ablation of septal ventricular
      tachycardia using 2 ablation catheters.

PMID- 24333924
TI  - Pause-dependent normalization of ST-segment elevation during the ajmaline test in
      a patient with Brugada syndrome.

PMID- 24333927
TI  - Topological organization of the human brain functional connectome across the
      lifespan.
AB  - Human brain function undergoes complex transformations across the lifespan. We
      employed resting-state functional MRI and graph-theory approaches to
      systematically chart the lifespan trajectory of the topological organization of
      human whole-brain functional networks in 126 healthy individuals ranging in age
      from 7 to 85 years. Brain networks were constructed by computing Pearson's
      correlations in blood-oxygenation-level-dependent temporal fluctuations among
      1024 parcellation units followed by graph-based network analyses. We observed
      that the human brain functional connectome exhibited highly preserved non-random
      modular and rich club organization over the entire age range studied. Further
      quantitative analyses revealed linear decreases in modularity and inverted-U
      shaped trajectories of local efficiency and rich club architecture. Regionally
      heterogeneous age effects were mainly located in several hubs (e.g., default
      network, dorsal attention regions). Finally, we observed inverse trajectories of
      long- and short-distance functional connections, indicating that the
      reorganization of connectivity concentrates and distributes the brain's
      functional networks. Our results demonstrate topological changes in the whole
      brain functional connectome across nearly the entire human lifespan, providing
      insights into the neural substrates underlying individual variations in behavior
      and cognition. These results have important implications for disease connectomics
      because they provide a baseline for evaluating network impairments in age-related
      neuropsychiatric disorders. 

PMID- 24333928
TI  - Expression patterns of atrial natriuretic peptide and its receptors within the
      cochlear spiral ganglion of the postnatal rat.
AB  - The spiral ganglion, which is primarily composed of spiral ganglion neurons and
      satellite glial cells, transmits auditory information from sensory hair cells to
      the central nervous system. Atrial natriuretic peptide (ANP), acting through
      specific receptors, is a regulatory peptide required for a variety of cardiac,
      neuronal and glial functions. Although previous studies have provided direct
      evidence for the presence of ANP and its functional receptors (NPR-A and NPR-C)
      in the inner ear, their presence within the cochlear spiral ganglion and their
      regulatory roles during auditory neurotransmission and development is not known.
      Here we investigated the expression patterns and levels of ANP and its receptors
      within the cochlear spiral ganglion of the postnatal rat using immunofluorescence
      and immunoelectron microscopy techniques, reverse transcription-polymerase chain
      reaction and Western blot analysis. We have demonstrated that ANP and its
      receptors colocalize in both subtypes of spiral ganglion neurons and in
      perineuronal satellite glial cells. Furthermore, we have analyzed differential
      expression levels associated with both mRNA and protein of ANP and its receptors
      within the rat spiral ganglion during postnatal development. Collectively, our
      research provides direct evidence for the presence and synthesis of ANP and its
      receptors in both neuronal and non-neuronal cells within the cochlear spiral
      ganglion, suggesting possible roles for ANP in modulating neuronal and glial
      functions, as well as neuron-satellite glial cell communication, within the
      spiral ganglion during auditory neurotransmission and development. 

PMID- 24333926
TI  - White matter connectivity and aerobic fitness in male adolescents.
AB  - Exercise has been shown to have positive effects on the brain and behavior
      throughout various stages of the lifespan. However, little is known about the
      impact of exercise on neurodevelopment during the adolescent years, particularly
      with regard to white matter microstructure, as assessed by diffusion tensor
      imaging (DTI). Both tract-based spatial statistics (TBSS) and tractography-based
      along-tract statistics were utilized to examine the relationship between white
      matter microstructure and aerobic exercise in adolescent males, ages 15-18.
      Furthermore, we examined the data by both (1) grouping individuals based on
      aerobic fitness self-reports (high fit (HF) vs. low fit (LF)), and (2) using VO2
      peak as a continuous variable across the entire sample. Results showed that HF
      youth had an overall higher number of streamline counts compared to LF peers,
      which was driven by group differences in corticospinal tract (CST) and anterior
      corpus callosum (Fminor). In addition, VO2 peak was negatively related to FA in
      the left CST. Together, these results suggest that aerobic fitness relates to
      white matter connectivity and microstructure in tracts carrying frontal and motor
      fibers during adolescence. Furthermore, the current study highlights the
      importance of considering the environmental factor of aerobic exercise when
      examining adolescent brain development. 

PMID- 24333929
TI  - The effects of noise vocoding on speech quality perception.
AB  - Speech perception depends on access to spectral and temporal acoustic cues.
      Temporal cues include slowly varying amplitude changes (i.e. temporal envelope,
      TE) and quickly varying amplitude changes associated with the center frequency of
      the auditory filter (i.e. temporal fine structure, TFS). This study quantifies
      the effects of TFS randomization through noise vocoding on the perception of
      speech quality by parametrically varying the amount of original TFS available
      above 1500Hz. The two research aims were: 1) to establish the role of TFS in
      quality perception, and 2) to determine if the role of TFS in quality perception
      differs between subjects with normal hearing and subjects with sensorineural
      hearing loss. Ratings were obtained from 20 subjects (10 with normal hearing and
      10 with hearing loss) using an 11-point quality scale. Stimuli were processed in
      three different ways: 1) A 32-channel noise-excited vocoder with random envelope
      fluctuations in the noise carrier, 2) a 32-channel noise-excited vocoder with the
      noise-carrier envelope smoothed, and 3) removal of high-frequency bands. Stimuli
      were presented in quiet and in babble noise at 18dB and 12dB signal-to-noise
      ratios. TFS randomization had a measurable detrimental effect on quality ratings
      for speech in quiet and a smaller effect for speech in background babble.
      Subjects with normal hearing and subjects with sensorineural hearing loss
      provided similar quality ratings for noise-vocoded speech. 

PMID- 24333930
TI  - Activated protein C inhibits amyloid beta production via promoting expression of
      ADAM-10.
AB  - Inhibition of Abeta production and clearance of senile plaques have been
      considered as potential strategies in the treatment of Alzheimer's disease (AD).
      Activated protein C (APC) is an important factor in the anticoagulant system.
      However, whether APC can influence the condition of a chronic neurodegenerative
      process, such as that present in AD, is unknown. In this study, we found that
      administration of APC on AD Tg2576 mice significantly reduced amyloid beta
      production and helped to facilitate cognitive improvement. APC could also reduce
      levels of Abeta40 and Abeta42 produced in APPswe cells, an AD cell model. Further
      results demonstrated that APC did not change the levels of Abeta-degrading
      enzymes, insulin-degrading enzyme (IDE), or neprilysin (NEP). Next, we found that
      APC promoted sAPPalpha and CTFalpha release and inhibited sAPPbeta and CTFbeta
      release, thereby indicating that APC could regulate Abeta secretion by shifting
      APP processing from the amyloidogenic pathway toward the nonamyloidogenic
      pathway. Correspondingly, further study revealed that ADAM-10 expression was
      increased by APC, suggesting that APC inhibits Abeta secretion through
      stimulating activity of alpha-secretase. These findings support the idea that APC
      could hold therapeutic potential in the treatment of AD. 

PMID- 24333931
TI  - Manganese cobaltite/polypyrrole nanocomposite-based air-cathode for sustainable
      power generation in the single-chambered microbial fuel cells.
AB  - Manganese cobaltite nanorods (MnCo2O4 NRs) were prepared and tested as potential
      air-cathode catalyst for the single-chambered microbial fuel cells (sMFC). The
      power generation of sMFC increases with MnCo2O4 NRs loading to the cathode. The
      Polypyrrole (PPy) and Vulcan XC were used as conducting support to the MnCo2O4
      NRs to form composites either by in situ or by mechanical mixing in the cathode
      fabrication. The cyclic voltammetry, linear sweep voltammetry and electrochemical
      impedance studies reveal that the in situ-MnCo2O4 NRs/PPy composite has higher
      catalytic activity than that of mechanically mixed-MnCo2O4NRs/PPy composite
      because of higher interfacial contact between MnCo2O4 NRs and PPy. The maximum
      volumetric power density with in situ-MnCo2O4 NRs/PPy, mechanically mixed-MnCo2O4
      NRs/PPy, MnCo2O4 NRs/Vulcan XC and catalyst-free (only Vulcan XC) cathode was
      measured to be 6.11, 5.05, 4.22, and 1.77 W/m(3), respectively, in the sMFC. This
      suggests that PPy is not only a better conducting support than that of
      conventionally used Vulcan XC but also the cathode composite fabrication process
      is important for enhanced performance. The synergetic effect of MnCo2O4 NRs and
      PPy was found to play an important role for the improved energy recovery and it
      could be applied as an efficient and inexpensive cathode catalyst for the sMFC.

PMID- 24333932
TI  - Stretchable electrochemical impedance sensors for intravascular detection of
      lipid-rich lesions in New Zealand White rabbits.
AB  - Flexible electronics have enabled catheter-based intravascular sensing. However,
      real-time interrogation of unstable plaque remains an unmet clinical challenge.
      Here, we demonstrate the feasibility of stretchable electrochemical impedance
      spectroscopy (EIS) sensors for endoluminal investigations in New Zealand White
      (NZW) rabbits on diet-induced hyperlipidemia. A parylene C (PAC)-based EIS sensor
      mounted on the surface of an inflatable silicone balloon affixed to the tip of an
      interrogating catheter was deployed (1) on the explants of NZW rabbit aorta for
      detection of lipid-rich atherosclerotic lesions, and (2) on live animals for
      demonstration of balloon inflation and EIS measurements. An input peak-to-peak AC
      voltage of 10 mV and sweeping-frequency from 300 kHz to 100 Hz were delivered to
      the endoluminal sites. Balloon inflation allowed EIS sensors to be in contact
      with endoluminal surface. In the oxidized low-density-lipoprotein (oxLDL)-rich
      lesions from explants of fat-fed rabbits, impedance magnitude increased
      significantly by 1.5-fold across the entire frequency band, and phase shifted ~5
      degrees  at frequencies below 10 kHz. In the lesion-free sites of the normal diet
      fed rabbits, impedance magnitude increased by 1.2-fold and phase shifted ~5
      degrees  at frequencies above 30 kHz. Thus, we demonstrate the feasibility of
      stretchable intravascular EIS sensors for identification of lipid rich lesions,
      with a translational implication for detecting unstable lesions.

PMID- 24333933
TI  - A novel fluorescent nanosensor for detection of heparin and heparinase based on
      CuInS2 quantum dots.
AB  - In this work, a novel fluorescence "turn off-on" nanosensor for the determination
      of heparin and heparinase based on CuInS2 quantum dots (QDs) was established.
      CuInS2 QDs (modified by l-cysteine) featuring amino groups were directly prepared
      in aqueous solution via a hydrothermal synthesis method. The amino groups on the
      surface of CuInS2 QDs can interact with sulfate and carboxylate groups in heparin
      via electrostatic interactions and hydrogen bonding, which led the fluorescence
      of CuInS2 QDs to "turn-off". However, the heparin could be hydrolyzed into small
      fragments in the presence of heparinase, which resulted in the fluorescence of
      CuInS2 QDs being recovered. Therefore, the addition of heparinase to the
      heparin/CuInS2 QDs system activated the fluorescence of CuInS2 QDs to "turn-on"
      state. Thus, the determination of heparin and heparinase could be achieved by
      monitoring the fluorescence "turn off-on". Under the optimum conditions, there
      was a good linear relationship between I/I0 (I and I0 were the fluorescence
      intensity of CuInS2 QDs in the presence and absence of heparin, respectively) and
      heparin concentration in the range of 0.05-15 MUmol L(-1) with the detection
      limit of 12.46 nmol L(-1). The linear detection for heparinase was in the range
      of 0.2-5 MUg mL(-1) with the detection limit of 0.07 MUg mL(-1). The proposed
      nanosensor was employed for the detection of heparin in fetal bovine serum
      samples with satisfactory results.

PMID- 24333934
TI  - Label-free functional assays of chemical receptors using a bioengineered cell
      based biosensor with localized extracellular acidification measurement.
AB  - New methods for functional assays of chemical receptors are highly essential for
      the research of chemical signal transduction mechanisms and for the development
      of chemical biosensors. This study described a novel bioengineered cell-based
      biosensor for label-free functional assays of chemical receptors by localized
      extracellular acidification measurement with a light-addressable potentiometric
      sensor (LAPS). A human taste receptor, hT2R4, and an olfactory receptor of
      Caenorhabditis elegans (C. elegans), ODR-10, were selected as models of chemical
      receptors, which were expressed on the plasma membrane of human embryonic kidney
      (HEK)-293 cells. The specific ligand binding function of expressed chemical
      receptors was monitored by localized extracellular acidification measurement
      using LAPS chip with a movable focused laser illuminating on the desired single
      cell. The function of expressed olfactory receptors was further validated using
      MDL12330A, which can specifically inhibit the activity of adenylyl cyclase. The
      obtained results indicate that both of chemical receptors were successfully
      expressed in HEK-293 cells and can be functionally assayed by this bioengineered
      cell-based biosensor that shows dose-dependent responses to the target ligands of
      chemical receptors. This bioengineered cell-based biosensor exhibits the
      sensitivity of 1.0 mV/s for hT2R4 assays, and 9.8 mV/s for ODR-10 assays. The
      negative control cells without any chemical receptor expression show no response
      to all the chemical stimuli tested. All the results demonstrate this
      bioengineered cell-based biosensor can be used to detect the interactions between
      chemical receptors and their ligands. This provides a valuable and promising
      approach for label-free functional assays of chemical receptors as well as for
      the research of other GPCRs.

PMID- 24333935
TI  - A novel electrochemical biosensor for monitoring protein nitration damage
      affected by NaNO2/hemin/H2O2.
AB  - A sensitive and facile electrochemical biosensor has been developed for
      monitoring the protein nitration damage affected by the nitro free radicals(NO2).
      The NO2 radicals is generated from hemin-catalyzed oxidation of nitrite (NO(-)2)
      in the presence of hydrogen peroxide (H2O2). In this work, nanocomposite films of
      graphene-gold nanoparticles (EG-AuNPs) were modified on the glassy carbon
      electrode by electropolymerization. Bovine serum albumin (BSA) was then further
      assembled on EG-AuNPs film through Au-S bond. The damage of BSA molecule was
      caused by the NO2 radicals which was generated from the NaNO2/hemin/H2O2
      nitration reagent. The differential pulse voltammetry was used to detect the
      damage of BSA molecule. Fluorescence spectra and circular dichroism spectrum
      further confirmed the nitration damage of BSA. Moreover, the lowest concentration
      at which the BSA damage was detected is 28.9 uM NO(-)2 or H2O2, and the volume
      ratio of NO(-)2 and H2O2 was 1:1 in the hemin/NO(-)2/H2O2 nitration reagent. The
      results demonstrated that the proposed electrochemical method can be used to
      detect protein damage affected by nitration reagent. The developed
      electrochemical biosensor is envisioned to have promising applications in protein
      damage studies.

PMID- 24333936
TI  - Simultaneous electrochemical detection of cervical cancer markers using reduced
      graphene oxide-tetraethylene pentamine as electrode materials and distinguishable
      redox probes as labels.
AB  - A novel, highly sensitive electrochemical immunoassay was proposed for the
      simultaneous determination of carcinoembryonic antigen (CEA) and squamous cell
      carcinoma antigen (SCCA) for the diagnosis of cervical cancer. Using an
      electrochemical analysis technique, two well-separated peaks were generated by
      neutral red and thionine, making the simultaneous detection of the two analytes
      on the electrode possible. Reduced graphene oxide-tetraethylene pentamine (rGO
      TEPA), containing more amino groups, was of benefit to immobilize the primary
      antibody (Ab1) through an amidation reaction. Au@mesoporous carbon CMK-3 was
      synthesized and incubated with two secondary antibodies (Ab2) and different redox
      probes (neutral red and thionine) to fabricate the electrochemical immunosensor
      label intending to improve the analytical performance of the immunosensor. The
      immunosensor was prepared with a sandwich structure based on the peak current
      change of neutral red and thionine before and after the antigen-antibody
      reaction. The results showed that the immunosensor had a wide linear range, low
      detection limit, good reproducibility and stability. The method has been applied
      to the analysis of serum samples with satisfactory results. 

PMID- 24333937
TI  - Paper-based batteries: a review.
AB  - There is an extensively growing interest in using paper or paper-like substrates
      for batteries and other energy storage devices. Due to their intrinsic
      characteristics, paper (or paper-like) batteries show outstanding performance
      while retaining low cost, multifunctionality, versatility, flexibility and
      disposability. In this overview, we review recent achievements in paper (or paper
      like) batteries as well as their applications. Various types of paper power
      devices are discussed including electrochemical batteries, biofuel cells, lithium
      ion batteries, supercapacitors, and nanogenerators. Further scientific and
      technological challenges in this field are also discussed. 

PMID- 24333938
TI  - A highly sensitive and selective homogenous assay for profiling microRNA
      expression.
AB  - A highly sensitive and selective homogeneous microRNA (miRNA) assay is described
      in this report. It is based on the cleavage of DNAzyme moieties from miRNA
      hybridized DNAzyme-capped capture probes (DZ-CPs) from magnetic beads by a duplex
      specific nuclease (DSN). After removing the magnetic beads together with the
      unreacted DZ-CPs by using a permanent magnet, amplified colorimetric detection of
      the target miRNA is realized through the cleaved DNAzyme moieties-catalyzed
      oxidation of 3,3',5,5'-tetramethylbenzidine. The exceptional amplification power
      of the DSN and the cumulative nature of the signal generation process permit the
      colorimetric detection of miRNAs down to subfemtomolar levels. The isothermal
      amplification scheme together with the simple assay protocol makes direct
      profiling miRNA in real-world samples possible. 

PMID- 24333939
TI  - Hot spots in mortality from drug poisoning in the United States, 2007-2009.
AB  - Over the past several years, the death rate associated with drug poisoning has
      increased by over 300% in the U.S. Drug poisoning mortality varies widely by
      state, but geographic variation at the substate level has largely not been
      explored. National mortality data (2007-2009) and small area estimation methods
      were used to predict age-adjusted death rates due to drug poisoning at the county
      level, which were then mapped in order to explore: whether drug poisoning
      mortality clusters by county, and where hot and cold spots occur (i.e., groups of
      counties that evidence extremely high or low age-adjusted death rates due to drug
      poisoning). Results highlight several regions of the U.S. where the burden of
      drug poisoning mortality is especially high. Findings may help inform efforts to
      address the growing problem of drug poisoning mortality by indicating where the
      epidemic is concentrated geographically. 

PMID- 24333940
TI  - Total synthesis of a sialyl Lewis(x) derivative for the diagnosis of cancer.
AB  - The total synthesis of aminoethyl glycoside of sialyl Lewis(x) (sLe(x)) is
      described. A galactose donor was condensed with a diol of glucosamine to afford
      regioselectively a beta1,4 linked disaccharide, which was further
      stereoselectively fucosylated to provide a protected Lewis(x) trisaccharide.
      After chemical modification, the trisaccharide was sialylated to give regio- and
      stereoselectively an azidoethyl glycoside of sLe(x). Finally, deprotection and
      azide reduction afforded the target compound. This compound will be coupled with
      protein and then be used to conduct further preclinical studies for the diagnosis
      of cancer. 

PMID- 24333941
TI  - Potential roles of vessel wall heparan sulfate proteoglycans in atherosclerosis.
AB  - Heparan sulfate proteoglycans (HSPGs) are present in several compartments and
      cell types in blood vessels. Their expression, as well as the activity of their
      degrading enzyme heparanase, are strongly regulated, with changes in gene
      expression, protein levels, and activity in response to environmental and
      metabolic stresses, including diabetes. HSPGs likely play an important role in
      the development and progression of atherosclerosis. Many functions of HSPGs, such
      as the promotion of monocyte adhesion, smooth muscle cell proliferation, and low
      density lipoproteins (LDL) binding, are determined by interactions between cells
      and specific regions of the HSPG core proteins. Here we review the role of HSPGs
      expressed in vascular wall in atherosclerotic vascular disease. 

PMID- 24333942
TI  - First-in-human experience with the Medtronic CoreValve Evolut R.
AB  - The CoreValve Evolut R with EnVeo R delivery catheter is a novel transcatheter
      heart valve (THV) system with enhanced features that have the potential to
      improve the safety of transcatheter aortic valve implantation (TAVI). The newly
      designed delivery catheter is 14 Fr-equivalent and thus expands the option of
      transfemoral TAVI to a greater proportion of patients. Most importantly, the
      EnVeo R delivery catheter allows the valve to be recaptured and repositioned
      during deployment, thus minimising the consequences of THV malposition.
      Furthermore, the nitinol frame of the CoreValve Evolut R has been redesigned for
      superior interaction, consistent radial force and optimised cover index across
      the sizing range, and conformability with the native annulus, thereby
      hypothetically reducing stress on the left bundle branch. Although large series
      with long-term follow-up are required to demonstrate the safety and efficacy of
      this device, we present the first human experience with the Evolut R system. 

PMID- 24333943
TI  - Successful and unsuccessful restrained eating. Does dispositional self-control
      matter?
AB  - In a random sample (N=1078) from the general population, this study examined
      whether individual differences in dispositional self-control can explain
      restrained eaters' success in controlling their weight. A regression analysis
      with body mass index (BMI) as dependent variable revealed a significant negative
      association between dispositional self-control and BMI, and a significant
      positive association between dietary restraint and BMI. These effects were
      qualified by a significant interaction between restraint and self-control. Among
      restrained eaters, the association between self-control and BMI was significantly
      more negative than among normal eaters. Furthermore, among female restrained
      eaters higher dispositional self-control scores were associated with BMIs within
      the normal-weight range (BMI<25) and lower dispositional self-control scores were
      associated with BMIs within the overweight range (BMI>25). Among male restrained
      eaters very high scores on dispositional self-control were associated with BMIs
      within the normal-weight range, whereas medium or low scores on self-control were
      associated with BMIs within the overweight range. Results suggest that high
      dispositional self-control facilitates successful restrained eating. 

PMID- 24333944
TI  - Oxidation mechanism and overall removal rates of endocrine disrupting chemicals
      by aquatic plants.
AB  - The purpose of this study was to evaluate experimentally and theoretically the
      oxidation mechanisms and overall removal rates of phenolic endocrine disrupting
      chemicals (EDCs) by aquatic plants. EDCs used in this study were bisphenol-A
      (BPA), 2,4-dichlorophenol (2,4-DCP), 4-tert-octylphenol (4-t-OP), and
      pentachlorophenol (PCP). Referring to reported detection levels in aquatic
      environments and contaminated sites, the feed concentration of each EDC was set
      from 1 to 100MUg/L. Experimental results showed that, except for PCP, phenolic
      EDCs were stably and concurrently removed by different types of aquatic plants
      over 70 days in long-term continuous treatments. Primal enzymes responsible for
      oxidation of BPA, 2,4-DCP, and 4-t-OP were peroxidases (POs). Moreover, enzymatic
      removal rates of BPA, 2,4-DCP, and 4-t-OP by POs were more than 2 orders of
      magnitude larger than those by aquatic plants. Assuming that overall removal
      rates of EDCs are controlled by mass transfer rates onto liquid films on the
      surface of aquatic plants, an electrochemical method based on the limiting
      current theory was developed to measure the mass transfer rates of EDCs. Because
      of extremely large removal rates of EDCs by POs, observed removal rates by
      aquatic plants were in reasonably good agreement with calculated results by a
      mathematical model developed based on an assumption that mass transfer limitation
      is a rate-limiting step. 

PMID- 24333945
TI  - Detection of the mycotoxin citrinin using silver substrates and Raman
      spectroscopy.
AB  - We detected a trace amount of the mycotoxin citrinin using surface-enhanced Raman
      scattering (SERS) on silver nanoparticle (Ag NP) surfaces. The SERS substrate on
      hydrophobic Teflon films was also introduced to observe the citrinin peaks. A
      broad band at ~1382cm(-1), which was ascribed to the symmetric carboxylate
      stretching mode, was observed in addition to an antisymmetric carboxylate
      stretching mode at ~1568cm(-1) in the Raman spectra. The spectral feature
      indicated that citrinin would adsorb on Ag NPs via its carboxylate form. Based on
      density functional theory (DFT) calculations, vibrational mode analysis was
      performed to compare the Raman spectra of citrinin. DFT calculations also
      predicted that a bidentate bridge configuration through O15 and O16 atoms in
      citrinin would be the most stable on three Ag atoms. After treating with Ag NPs,
      observation of citrinin peaks was attempted in fungal cells of Penicillium
      citrinum. This work may provide useful insights into the direct observation of
      the hazardous citrinin mycotoxin using SERS by understanding its adsorption
      behaviors on Ag surfaces. 

PMID- 24333946
TI  - Co-administration of hyaluronic acid with local anaesthetics shows lower
      cytotoxicity than local anaesthetic treatment alone in bovine articular
      chondrocytes.
AB  - OBJECTIVE: To study the effect of hyaluronic acid (HA) on local anaesthetic
      chondrotoxicity in vitro. METHODS: Chondrocytes were harvested from bovine
      femoral condyle cartilage and isolated using collagenase-containing media. At 24
      hours after seeding 15 000 cells per well onto a 96-well plate, chondrocytes were
      treated with media (DMEM/F12 + ITS), PBS, 1:1 lidocaine (2%):PBS, 1:1 bupivacaine
      (0.5%):PBS, 1:1 lidocaine (2%):HA, 1:1 bupivacaine (0. 5%):HA, or 1:1 HA:PBS for
      one hour. Following treatment, groups had conditions removed and 24-hour
      incubation. Cell viability was assessed using PrestoBlue and confirmed visually
      using fluorescence microscopy. RESULTS: Media-treated groups had a mean of
      1.55*10(4) cells/well (sem 783). All treated cells showed statistically
      significant reduced viability when compared with media alone (all p < 0.003).
      Cells treated with bupivacaine + HA (6.70*10(3) cells/well (sem 1.10*10(3)))
      survived significantly more than bupivacaine (2.44*10(3) cells/well (sem 830)) (p
      < 0.001). Lidocaine + HA (1.45*10(3) cells/well (sem 596)) was not significantly
      more cytotoxic than lidocaine (2.24*10(3) cells/well (sem 341)) (p = 0.999).
      There was no statistical difference between the chondrotoxicities of PBS
      (8.49*10(3) cells/well (sem 730) cells/well) and HA (4.75*10(3) cells/well (sem
      886)) (p = 0.294). CONCLUSIONS: HA co-administration reduced anaesthetic
      cytotoxicity with bupivacaine but not lidocaine, suggesting different mechanisms
      of injury between the two. Co-administered intra-articular injections of HA with
      bupivacaine, but not lidocaine, may protect articular chondrocytes from local
      anaesthetic-associated death. Cite this article: Bone Joint Res 2013;2:270-5.

PMID- 24333947
TI  - Response to letter to the editor.

PMID- 24333948
TI  - Remembering the dynamic changes in pain intensity and unpleasantness: a
      psychophysical study.
AB  - This study investigated the short-term memory of dynamic changes in acute pain
      using psychophysical methods. Pain intensity or unpleasantness induced by painful
      contact-heat stimuli of 8, 9, or 10s was rated continuously during the stimulus
      or after a 14-s delay using an electronic visual analog scale in 10 healthy
      volunteers. Because the continuous visual analog scale time courses contained
      large amounts of redundant information, a principal component analysis was
      applied to characterize the main features inherent to both the concurrent rating
      and retrospective evaluations. Three components explained about 90% of the total
      variance across all trials and subjects, with the first component reflecting the
      global perceptual profile, and the second and third components explaining finer
      perceptual aspects (eg, changes in slope at onset and offset and shifts in peak
      latency). We postulate that these 3 principal components may provide some
      information about the structure of the mental representations of what one
      perceives, stores, and remembers during the course of few seconds. Analysis
      performed on the components confirmed significant memory distortions and revealed
      that the discriminative information about pain dimensions in concurrent ratings
      was partly or completely lost in retrospective ratings. Importantly, our results
      highlight individual differences affecting these memory processes. These results
      provide further evidence of the important transformations underlying the
      processing of pain in explicit memory and raise fundamental questions about the
      conversion of dynamic nociceptive signals into a mental representation of pain in
      perception and memory. 

PMID- 24333949
TI  - Comparison of muscle and joint pressure-pain thresholds in patients with complex
      regional pain syndrome and upper limb pain of other origin.
AB  - Pain localized in the deep tissues occurs frequently in complex regional pain
      syndrome (CRPS). In addition, hyperalgesia to blunt pressure over muscles is
      common in CRPS, but it often appears in limb pain of other origin as well.
      Considering that 3-phase bone scintigraphy (TPBS) reveals periarticular enhanced
      bone metabolism in CRPS, joint-associated hyperalgesia to blunt pressure might be
      a more specific finding than hyperalgesia over muscles. In 34 patients with upper
      limb pain (18 CRPS, 16 non-CRPS; diagnosed in accordance to the Budapest
      criteria) and in 18 healthy controls, pressure-pain thresholds (PPT) were
      assessed bilaterally over the thenar (PPTThenar), the metacarpophalangeal
      (PPTMCP), and the proximal interphalangeal (PPTPIP) joints using a pressure
      algometer (Somedic, Sweden). Beforehand, all patients had received TPBS for
      diagnostic purposes independently of the study. Region-of-interest (ROI) ratios
      (mineralization phase) for the MCP and PIP, excluding fracture sites, were
      correlated with the PPT. In CRPS, all ROI ratios were significantly increased and
      all PPT of the affected hand were decreased compared to non-CRPS (PPTThenar:
      243+/-150kPa vs 358+/-197kPa, PPTMCP: 80+/-67kPa vs 159+/-93kPa, PPTPIP: 80+/
      56kPa vs 184+/-110kPa; P<.01) and controls (PPTThenar: 478+/-106kPa, PPTMCP:
      254+/-50kPa, PPTPIP: 275+/-76kPa; P<.01). A PPTThenar below 293kPa revealed 77%
      sensitivity but only 63% specificity, whereas a PPTPIP below 102kPa had 82%
      sensitivity and 94% specificity to identify CRPS. Only in CRPS were PPTMCP and
      PPTPIP correlated significantly inversely with the ROI ratio (MCP: r=-0.439, PIP:
      r=-0.447). PPTPIP shows higher specificity for CRPS type I than PPTThenar without
      loss of sensitivity. Therefore, measurement of joint PPT could be a noninvasive
      diagnostic tool reflecting increased bone metabolism assessed by TPBS as a sign
      of bone pathophysiology. 

PMID- 24333950
TI  - Response to letter to the editor.

PMID- 24333951
TI  - A fifth of Dutch support assisted suicide for people "tired of living".

PMID- 24333952
TI  - Transcription factor seeks DNA-cognate site preferred.

PMID- 24333953
TI  - Involvement of cardiolipin in tBID-induced activation of BAX during apoptosis.
AB  - Permeabilization of the outer mitochondrial membrane constitutes an essential
      step in response to a wide range of apoptotic stimuli. Pro-apoptotic members of
      the BCL-2 family such as BAX and BAK are responsible for disrupting the integrity
      of the mitochondrial outer membrane, thereby allowing the release of apoptogenic
      factors including cytochrome c, which activate caspases in the cytosol. How BAX
      and BAK are activated during apoptosis is still not fully understood. Cooperation
      between tBID and the mitochondrial-specific phospholipid cardiolipin has been
      suggested to promote BAX or BAK oligomerization. Here we review the evidence for
      and against a role for cardiolipin in BAX and BAK activation and in the
      subsequent onset of apoptosis. 

PMID- 24333954
TI  - Comparison of the MesoScale Discovery and Luminex multiplex platforms for
      measurement of urinary biomarkers in a cisplatin rat kidney injury model.
AB  - INTRODUCTION: In the past years several new urinary nephrotoxicity biomarkers
      have been qualified for use in preclinical studies by the FDA and EMA.
      Subsequently, kits have been developed to measure these urinary biomarkers on
      multiplex platforms such as the electro-chemiluminescent based immunoassay from
      MesoScale Discovery (MSD) and the bead-based immunoassay using Luminex xMAP
      technology (LMX). The aim of the present study was to compare the two multiplex
      platforms with respect to the capability of their qualified urinary biomarker
      panels to measure an increase of these biomarkers relative to histopathological
      changes in an animal model of nephrotoxicity. METHODS: For comparison of the two
      platforms we used urine samples from a study with the well-characterized
      nephrotoxin cisplatin (Cp) in male Wistar rats. The following five biomarkers
      were measured on both platforms: glutathione S-transferase alpha (alphaGST),
      clusterin (CLU), kidney injury molecule-1 (KIM-1), neutrophil gelatinase
      associated lipocalin (NGAL, a.k.a. lipocalin-2) and osteopontin (OPN). The
      measurements were compared with respect to both the fold increase observed for
      each biomarker and the absolute concentrations measured in relation to
      traditional endpoints for nephrotoxicity in clinical pathology and
      histopathology. RESULTS: The platform comparison revealed the expected increases
      of urinary biomarkers after Cp treatment with similar results at the fold change
      level enabling consistent detection of kidney injury. The comparison of the
      absolute concentrations of biomarkers measured in the two platforms showed
      differences, the extent of which was analyte-dependent. DISCUSSION: By comparison
      of two widely used multiplex platforms, MSD and LMX, for the detection of renal
      toxicity biomarkers in urine, we observed the expected increases of these
      biomarkers in response to Cp administration. Depending on the marker, significant
      differences could be found when comparing the absolute concentrations thus
      suggesting that baseline levels for each platform will have to be set separately.

PMID- 24333955
TI  - A quantitative bifunctional in vitro potency assay for botulinum neurotoxin
      serotype A.
AB  - INTRODUCTION: Botulinum neurotoxin type A (BoNTA) is one of seven serotypes
      produced by Clostridium botulinum (types A thru G) and is the serotype most
      widely used to treat both cosmetic and medical conditions. Potency for botulinum
      toxin preparations is expressed in mouse LD50 units. There is a need to develop a
      non-animal based replacement for this potency assay. METHODS: An in vitro potency
      assay measuring BoNTA activity has been developed that addresses both BoNTA heavy
      chain binding to its cell receptor SV2C and BoNTA light chain enzymatic activity
      in cleaving SNAP-25, an intracellular protein essential in neurotransmitter
      release. This bifunctional assay utilizes a 96 well microtiter format and well
      defined reagents. Assay characterization determined that the relative standard
      deviation for intermediate precision was less than 10%. RESULTS: The assay
      standard curve covers the range of BoNTA concentrations from 0.0624 to 32 ng/mL.
      Specificity was demonstrated with purified BoNTA heavy chain which inhibited the
      activity in a dose dependent manner. A correlation between this bifunctional
      assay and the mouse LD50 potency assay was demonstrated.

PMID- 24333956
TI  - Fracture resistance and cuspal deflection of incompletely excavated teeth.
AB  - OBJECTIVES: Incomplete excavation reduces the risk of pulpal complications, but
      doubts remain regarding the mechanical properties of incompletely excavated
      teeth. Remaining carious dentine is suspected to not sufficiently support the
      restoration and to reduce bond strengths between the tooth and the restoration,
      with effects possibly varying depending on the depth of the remaining caries
      lesion. This study investigated fracture resistance (FR) and cuspal deflection
      (CD) of premolars after leaving or removing demineralized dentine in vitro.
      METHODS: In 48 premolars, shallow and deep artificial lesions (depths [mean +/-
      SD] of 64 +/- 18 MUm and 771 +/- 176 MUm) were created on pulpo-axial walls of
      standardised mesial-distal-occlusal cavities. Demineralized dentine was either
      removed or left before adhesively restoring the tooth (n=12/group). Restored
      teeth were submitted to thermo-mechanical cycling. CD was subsequently measured
      at loads of 200 N and 400 N, and teeth submitted to occlusal-perpendicular
      loading until fracturing occurred. RESULTS: FR was not significantly different
      between teeth with or without remaining demineralized dentine regardless of the
      lesion depth (p>0.30, t-test). Irrespective of the removal technique, teeth with
      deep lesions showed significantly decreased FR (p <= 0.001). In contrast, CD was
      significantly increased in teeth with remaining demineralized dentine compared
      with completely excavated teeth (p <= 0.05; Mann-Whitney test). CONCLUSIONS:
      Remaining demineralized dentine did not significantly decrease the fracture
      resistance of premolars in vitro. Effects of increased cuspal deflection on
      restoration margins should be assessed. This study showed no indication that
      incomplete excavation increases the risk of non-pulpal complications. CLINICAL
      SIGNIFICANCE: Incomplete caries removal seems suitable to treat especially deep
      lesions. Leaving demineralized dentine does not seem to affect the fracture
      resistance of incompletely excavated teeth regardless of the lesion depth.

PMID- 24333957
TI  - Effect of low-fluoride toothpastes combined with hexametaphosphate on in vitro
      enamel demineralization.
AB  - OBJECTIVES: The aim of this study was to evaluate the anticaries effect of low
      fluoride toothpastes combined with hexametaphosphate (HMP) on enamel
      demineralization. METHODS: Bovine enamel blocks were subjected to pH cycling and
      treatment with toothpaste's slurries (15 groups; 2*/day). Toothpaste mixtures
      contained the following: no fluoride (F) plus HMP (from 0 to 3.0%); 250ppm F plus
      HMP (from 0 to 3.0%); 500ppm F; 1100ppm F; and a commercial toothpaste (1100ppm
      F). After pH cycling, surface and cross-sectional hardness, as well as F present
      in the enamel were determined. The demineralization depth was analyzed using
      polarized light microscopy. The variables were subjected to 1-way ANOVA, followed
      by Student-Newman-Keuls' test (p<0.05). RESULTS: In the absence of fluoride, 0.5%
      HMP promoted the lowest mineral loss and its effect was similar to that of a
      250ppm F toothpaste (p>0.05). The combination of 0.5% HMP and 250ppm F resulted
      in lower mineral loss (p<0.05) and similar lesion depth when compared to the
      1100ppm F toothpaste (p>0.05). CONCLUSION: To conclude, the combination of 0.5%
      HMP and 250ppm fluoride in a toothpaste has a similar inhibitory effect on enamel
      demineralization in vitro when compared to a toothpaste containing 1100ppm F.
      CLINICAL SIGNIFICANCE: The anticaries effect of toothpaste containing 250ppm F
      combined with 0.5% HMP was similar to that of a 1100ppm F toothpaste, despite the
      4-fold difference in F concentration. Although such effects still need to be
      demonstrated in clinical studies, it may be a viable alternative for preschool
      children.

PMID- 24333958
TI  - New finding of an anti-TB compound in the genus Marsypopetalum (Annonaceae) from
      a traditional herbal remedy of Laos.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: There is widespread use of traditional herbal
      remedies in the Lao PDR (Laos). It is common practice to treat many diseases with
      local plants. This research project documented and analysed some of these
      traditional remedies used to treat symptoms of tuberculosis (TB). MATERIALS AND
      METHODS: This research was executed by interviewing healers about plants used
      traditionally to treat the symptoms of TB. Samples of some of the plants were
      collected, and extracts of 77 species were submitted to various in vitro assays
      in order to determine the amount of growth inhibition of virulent Mycobacterium
      tuberculosis H37Rv (Mtb), as opposed to other microbes and mammalian Vero cells.
      RESULTS: Interviews took place with 58 contemporary healers in 5 different
      provinces about plants currently used, giving a list of 341 plants. Bioassay
      guided fractionation was performed on Marsypopetalum modestum (Pierre) B. Xue and
      R.M.K. Saunders (Annonaceae), leading to the isolation of dipyrithione, an anti
      mycobacterial compound isolated for the first time from the genus Marsypopetalum
      through this research. CONCLUSIONS: This research has helped to increase
      awareness of Laos' rich diversity of medicinal plants and will hopefully provide
      incentive to preserve the undeveloped forested areas that remain, which still
      hold a wealth of medical information for future discoveries.

PMID- 24333959
TI  - Trapa natans L. root extract suppresses hyperglycemic and hepatotoxic effects in
      STZ-induced diabetic rat model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Trapa natans L. has a folkloric reputation as
      nutrient, appetizer and astringent. Its utility as antidiabetic, anticancer,
      diuretic, aphrodisiac, antidiarrhoeal and in many other maladies is well reported
      in the literature. Therefore, the present study has been carried out to study the
      antihyperglycemic effect of root extract of Trapa natans L. and its various
      fractions. Furthermore, hepatotoxic effects and lipid peroxidation risks have
      also been evaluated. METHODS: The ethanol extract and its successive fractions
      obtained from roots of Trapa natans have been administered in sucrose loaded and
      STZ- induced diabetic Wistar rats at doses of 50, 100 and 200mg/kg b.w.
      Glibenclamide was used as positive control. The evaluation of protective effects
      of extract as well as fractions against hepatotoxicity and lipid peroxidation at
      600mg/kg b.w. has also been carried out. RESULTS: The methanol fraction emerged
      as the most potent antihyperglycemic fraction. It has also been found that the
      ethanolic extract as well as its fractions did not cause any lipid peroxidation
      and hepatotoxicity risks. CONCLUSION: It can be concluded that the intense
      investigations of the methanol fraction obtained from Trapa natans root extract
      can be done to provide an alternative natural therapy for hyperglycemia.

PMID- 24333960
TI  - Lepidium meyenii (Maca) enhances the serum levels of luteinising hormone in
      female rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lepidium meyenii (Maca) is traditionally employed
      in the Andean region for its supposed fertility benefits. This study investigated
      the effect of Maca on the serum pituitary hormone levels during the pro-oestrus
      phase. MATERIALS AND METHODS: Maca powder was made from the tubers of Lepidium
      meyenii Walp collected, dried, and reduced to powder at the plantation in Junin
      Plateau and was purchased from Yamano del Peru SAC. The Maca powder was
      identified by chemical profiling and taxonomic methods. Two groups of female
      Sprague-Dawley rats were provided feed with normal feed containing 5%, 25%, or
      50% Maca powder ad libitum for 7 weeks. At 1800h of the proestrus stage, the rats
      were euthanised, and blood samples were collected for serum isolation. The serum
      pituitary hormone levels were measured using enzyme-linked immunosorbent assays
      (ELISAs). RESULTS: No significant differences in feed intake or growth rate were
      observed among the rats. During the pro-oestrus stage, a 4.5-fold increase
      (P<0.01) in luteinising hormone (LH) and a 19-fold increase (P<0.01) in follicle
      stimulating hormone (FSH) were observed in the sera of rats fed with 50% Maca
      powder compared with the control rats. No significant differences were observed
      in the levels of the other pituitary hormones, including growth hormone (GH),
      prolactin (PRL), adrenocorticotropic hormone (ACTH), and thyroid-stimulating
      hormone (TSH). A dose-dependent increase of LH serum levels was observed within
      the range of 3-30g Maca/kg. Furthermore, the enhancement of the LH serum levels
      was specific to the pro-oestrus LH surge. CONCLUSIONS: The present study
      demonstrates that Maca uniquely enhances the LH serum levels of pituitary
      hormones in female rats during the pro-oestrus LH surge and acts in a
      pharmacological, dose-dependent manner. These findings support the traditional
      use of Maca to enhance fertility and suggest a potential molecular mechanism
      responsible for its effects.

PMID- 24333961
TI  - Antibacterial activity of the roots, stems and leaves of Alchornea floribunda.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Alchornea floribunda Mull. Arg. is used in
      traditional medicine across Africa for the treatment of bacterial, fungal,
      parasitic and inflammatory disorders. AIM OF THE STUDY: To evaluate the
      antibacterial activity of the crude extracts of different plant parts in order to
      provide a scientific rationale for the proposed broad efficacy of Alchornea
      floribunda in the treatment of bacterial infections. MATERIALS AND METHODS:
      Extracts of roots, stems and leaves were prepared using solvents of various
      polarities in order to extract a wide range of phytochemicals. The antibacterial
      activity of these crude extracts was evaluated by micro-dilution assay, against
      Gram-positive (i.e. Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus
      and Staphylococcus saprophyticus) as well as Gram-negative (i.e. Escherichia
      coli, Klebsiella pneumoniae, Moraxella catarrhalis and Proteus mirabilis)
      bacteria. RESULTS: Generally, the ethanol (EtOH), methanol (MeOH), ethyl acetate
      (EtOAc) and chloroform (CHCl3) extracts demonstrated the best activities, with
      the leaves exhibiting the highest average activity for six of the eight
      pathogens. Of these, the ethanolic leaf extract was the most active against
      Staphylococcus aureus with an MIC value of 50ug/mL. Some other notable activity
      was observed for the ethyl acetate and chloroform root extracts against
      Staphylococcus aureus (50ug/mL), and for selected stem extracts against
      Staphylococcus aureus (50ug/mL), Klebsiella pneumoniae (63ug/mL) and
      Staphylococcus saprophyticus (63ug/mL). CONCLUSION: This study demonstrates the
      promising antibacterial activity of Alchornea floribunda against both Gram
      positive and Gram-negative bacteria responsible for gastrointestinal, skin,
      respiratory and urinary ailments, and validates its use in the ethnopharmacology
      of the region.

PMID- 24333962
TI  - Cnidoscolus chayamansa Mc Vaugh, an important antioxidant, anti-inflammatory and
      cardioprotective plant used in Mexico.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cnidoscolus chayamansa Mc Vaugh (Euphorbiaceae)
      is commonly known as 'chaya' in Central America. In South East Mexico, because of
      its high nutritional values, is an important part of the diet of many indigenous
      communities. Chaya is also used as a traditional remedy for the treatment of
      diabetes, rheumatism, gastrointestinal disorders and inflammation-related
      diseases. Although Cnidoscolus chayamansa is one of most used and valued
      medicinal plants, only few studies on documenting its pharmacological properties
      can be found. MATERIALS AND METHODS: Dried leaves of Cnidoscolus chayamansa were
      subjected to a successive maceration using Hex, EtOAc and EtOH. The antioxidant
      activities of the extracts were tested using the DPPH radical scavenging, Ferric
      reducing/antioxidant power and total phenolic content assays. To determine the
      anti-inflammatory activity, the TPA-induced mouse ear edema and the carrageenan
      induced mouse paw edema assays were used. The cardioprotective effects of the
      EtOH extract was determined using the ischemia/reperfusion (I/R) rat model.
      Finally, the acute toxicity was determined using Lorke's method. RESULTS: The
      results showed a similar anti-inflammatory activity (~30%) for all extracts but
      only the EtOAc extract showed relevant activity when applied intraperitoneally.
      When tested for their antioxidant activity none of the extracts showed a
      significant activity suggesting that the antinflammatory activity is not related
      to a direct free radical scavenging of the extracts. Additionally, the EtOH
      extract showed a strong cardioprotective effect at 500mg/kg when given orally.
      Both the EtOAc and the EtOH extract have a LD50 >5g/kg, confirming their safety
      in acute oral administration. CONCLUSIONS: All these results are relevant for a
      better understanding of the therapeutic used of Cnidoscolus chayamansa in the
      Mexican traditional medicine and highlights its cardioprotective potential.

PMID- 24333963
TI  - Antinociceptive and anti-inflammatory activities of extract and two isolated
      flavonoids of Carthamus tinctorius L.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Safflower (Carthamus tinctorius L.) has been long
      used both in the traditional system and folk medicine as an analgesic anti
      inflammatory agent in China. The aim of the study was to evaluate the
      antinociceptive and anti-inflammatory activities of hydroalcoholic extract (HE)
      and two isolated kaempferol glycosides of Carthamus tinctorius L. to provide
      experimental evidence for its traditional use. MATERIALS AND METHODS:
      Antinociceptive effects of HE, kaempferol 3-O-rutinoside (K-3-R) and kaempferol 3
      O-glucoside (K-3-G) were assessed in mice using the acetic acid-induced writhing
      test, formalin test and cinnamaldehyde test. The anti-inflammatory effects of HE,
      K-3-R and K-3-G were determined in two animal models: carrageenan-induced paw
      edema and xylene-induced ear edema. RESULTS: The HPLC analysis showed the
      presence of K-3-R and K-3-G in Carthamus tinctorius L. HE (500 and 1000mg/kg) as
      well as K-3-R and K-3-G (150, 300 and 600mg/kg) produced significant inhibition
      on nociception induced by acetic acid and formalin. Oral treatment of HE, K-3-R
      and K-3-G at all doses significantly reduced both the nociceptive response and
      cinnamaldehyde-induced paw edema, effect that was superior to aspirin. In anti
      inflammatory tests, HE and K-3-G significantly inhibited the paw edema during the
      both phases of carrageenan-induced inflammation while K-3-G suppressed the late
      phase inflammation only. HE (400 and 800mg/kg) and K-3-G (200, 400, 800mg/kg)
      produced significant dose-dependent inhibition of xylene-induced ear edema
      development. K-3-R only suppressed ear edema formation at a high dose (800mg/kg).
      CONCLUSIONS: These results demonstrate that Carthamus tinctorius L. extract
      possess remarkable antinociceptive and anti-inflammatory activities which may be
      due to K-3-R and K-3-G at least in part, supporting the folkloric usage of the
      plant to treat various inflammatory and pain diseases.

PMID- 24333964
TI  - [Immunotherapies and targeted therapies in medical oncology].
AB  - New immunotherapies, also called "immune checkpoints", are promising and showed
      interesting antitumoral activities in particular in advanced setting of melanoma,
      clear cell renal cancer or non-small cell lung carcinoma. These treatments
      include ipilimumab, anti-PD-1 and anti-PD-L1. There is a strong rational for
      combination of immunotherapies and targeted therapies. This review is dedicated
      to expose the theorical issues and preclinical data of such combinations. This
      review examined the impact of immunotherapies on transduction pathways and
      modification of immunity related to targeted therapies. First clinical data form
      early drug development studies showed the difficulties observed with such
      combination and limitating toxicities. Finally, potential interesting
      combinations are overviewed with an emphasis on sequential treatments. 

PMID- 24333965
TI  - Role of SIRT1 and AMPK in mesenchymal stem cells differentiation.
AB  - The differentiation capabilities of mesenchymal stem cells (MSCs) compromise with
      age and with in vitro passages which could impair the efficacy of cell therapy
      and tissue engineering. However, how to maintain these capabilities is not fully
      understood. Calorie restriction (CR, decreasing caloric intake by 30-40%) could
      extend longevity and reduce aging-related diseases. Recent studies revealed that
      CR could influence the lineage determination of stem cells including MSCs. Two
      important mediators of CR might be silent mating type information regulation 2
      homolog 1 (SIRT1), a NAD(+)-dependent deacetylase, and AMP-activated protein
      kinase (AMPK), an energy-sensing kinase. Evidences are mounting that both SIRT1
      and AMPK play important roles in cell fate determination of MSCs. Herein, we
      intend to sum up our understanding about the role of SIRT1 and AMPK in osteogenic
      and adipogenic potential of MSCs. Metabolic process of MSCs differentiation and
      the putative interplay of SIRT1 and AMPK in this process was also discussed. 

PMID- 24333966
TI  - Pushing product formation to its limit: metabolic engineering of Corynebacterium
      glutamicum for L-leucine overproduction.
AB  - Using metabolic engineering, an efficient L-leucine production strain of
      Corynebacterium glutamicum was developed. In the wild type of C. glutamicum, the
      leuA-encoded 2-isopropylmalate synthase (IPMS) is inhibited by low L-leucine
      concentrations with a K(i) of 0.4 mM. We identified a feedback-resistant IMPS
      variant, which carries two amino acid exchanges (R529H, G532D). The corresponding
      leuA(fbr) gene devoid of the attenuator region and under control of a strong
      promoter was integrated in one, two or three copies into the genome and combined
      with additional genomic modifications aimed at increasing L-leucine production.
      These modifications involved (i) deletion of the gene encoding the repressor LtbR
      to increase expression of leuBCD, (ii) deletion of the gene encoding the
      transcriptional regulator IolR to increase glucose uptake, (iii) reduction of
      citrate synthase activity to increase precursor supply, and (iv) introduction of
      a gene encoding a feedback-resistant acetohydroxyacid synthase. The production
      performance of the resulting strains was characterized in bioreactor
      cultivations. Under fed-batch conditions, the best producer strain accumulated L
      leucine to levels exceeding the solubility limit of about 24 g/l. The molar
      product yield was 0.30 mol L-leucine per mol glucose and the volumetric
      productivity was 4.3 mmol l-1 h-1. These values were obtained in a defined
      minimal medium with a prototrophic and plasmid-free strain, making this process
      highly interesting for industrial application.

PMID- 24333967
TI  - Birth-date dependent arrangement of spinal enkephalinergic neurons: evidence from
      the preproenkephalin-green fluorescent protein transgenic mice.
AB  - Enkephalin (ENK) has been postulated to play important roles in modulating
      nociceptive transmission, and it has been proved that ENKergic neurons acted as a
      critical component of sensory circuit in the adult spinal cord. Revealing the
      developmental characteristics of spinal ENKergic neurons will be helpful for
      understanding the formation and alteration of the sensory circuit under pain
      status. However, the relationship between the embryonic birth date and the adult
      distribution of ENKergic neurons has remained largely unknown due to the
      difficulties in visualizing the ENKergic neurons clearly. Taking advantage of the
      preproenkephalin-green fluorescent protein (PPE-GFP) transgenic mice in
      identifying ENKergic neurons, we performed the current birth-dating study and
      examined the spinal ENKergic neurogenesis. The ENKergic neurons born on different
      developmental stages and their final location during adulthood were investigated
      by combining bromodeoxyuridine (BrdU) incorporation and GFP labeling. The spinal
      ENKergic neurogenesis was restricted at E9.5 to E14.5, and fitted in the same
      pattern of spinal neurogenesis. Further comparative analysis revealed that spinal
      ENKergic neurons underwent heterogeneous characteristics. Our study also
      indicated that the laminar arrangement of ENKergic neurons in the superficial
      spinal dorsal horn depended on the neurogenesis stages. Taken together, the
      present study suggested that the birth date of ENKergic neurons is one
      determinant for their arrangement and function. 

PMID- 24333968
TI  - Target-dependent expression of the netrin-1 receptor, UNC5C, in projection
      neurons of the ventral tegmental area.
AB  - We have shown previously that the netrin-1 receptor, unc-5 homologue C (UNC5C),
      is expressed by ventral tegmental area (VTA) dopamine (DA) neurons of rodents,
      but only from adolescence onwards (Manitt et al., 2010; Auger et al., 2013). The
      goal of this study was to characterize the expression of UNC5C by these neurons.
      Specifically, we assessed whether UNC5C expression is selective to DA neurons
      that project to the medial prefrontal cortex (mPFC), which undergo significant
      maturation during the adolescent period. To this end, we injected fluorescent
      retrograde tracer beads into the mPFC, nucleus accumbens (NAcc) core, or NAcc
      lateral shell of adult male wild-type C57Bl/6J mice and processed their brains
      for tyrosine hydroxylase (TH) and UNC5C immunofluorescence 2-3weeks later. VTA
      neurons with any combination of these immunolabels were visualized and counted
      using optical fractionator stereology. Our analysis revealed two main findings:
      (1) there are no differences in the proportions of UNC5C-positive DA neurons
      projecting to the mPFC, NAcc core, or NAcc lateral shell, and (2) the proportion
      of non-DA UNC5C-positive neurons targeting the mPFC is greater than the
      proportions of non-DA UNC5C-positive neurons targeting the NAcc core or lateral
      shell. These findings show that, contrary to our hypothesis, DA neurons
      projecting to the mPFC do not express UNC5C selectively. However, UNC5C
      expression by non-DA VTA neurons is predominantly found in those projecting to
      the mPFC and, as such, may play a role in their function. 

PMID- 24333969
TI  - Diffusion tensor imaging and MR morphometry of the central auditory pathway and
      auditory cortex in aging.
AB  - Age-related hearing loss (presbycusis) is caused mainly by the hypofunction of
      the inner ear, but recent findings point also toward a central component of
      presbycusis. We used MR morphometry and diffusion tensor imaging (DTI) with a 3T
      MR system with the aim to study the state of the central auditory system in a
      group of elderly subjects (>65years) with mild presbycusis, in a group of elderly
      subjects with expressed presbycusis and in young controls. Cortical
      reconstruction, volumetric segmentation and auditory pathway tractography were
      performed. Three parameters were evaluated by morphometry: the volume of the gray
      matter, the surface area of the gyrus and the thickness of the cortex. In all
      experimental groups the surface area and gray matter volume were larger on the
      left side in Heschl's gyrus and planum temporale and slightly larger in the gyrus
      frontalis superior, whereas they were larger on the right side in the primary
      visual cortex. Almost all of the measured parameters were significantly smaller
      in the elderly subjects in Heschl's gyrus, planum temporale and gyrus frontalis
      superior. Aging did not change the side asymmetry (laterality) of the gyri. In
      the central part of the auditory pathway above the inferior colliculus, a trend
      toward an effect of aging was present in the axial vector of the diffusion (L1)
      variable of DTI, with increased values observed in elderly subjects. A trend
      toward a decrease of L1 on the left side, which was more pronounced in the
      elderly groups, was observed. The effect of hearing loss was present in subjects
      with expressed presbycusis as a trend toward an increase of the radial vectors
      (L2L3) in the white matter under Heschl's gyrus. These results suggest that in
      addition to peripheral changes, changes in the central part of the auditory
      system in elderly subjects are also present; however, the extent of hearing loss
      does not play a significant role in the central changes. 

PMID- 24333970
TI  - Motor execution and motor imagery: a comparison of functional connectivity
      patterns based on graph theory.
AB  - Motor execution and imagery (ME and MI), as the basic abilities of human beings,
      have been considered to be effective strategies in motor skill learning and motor
      abilities rehabilitation. Neuroimaging studies have revealed several critical
      regions from functional activation for ME as well as MI. Recently, investigations
      have probed into functional connectivity of ME; however, few explorations
      compared the functional connectivity between the two tasks. With betweenness
      centrality (BC) of graph theory, we explored and compared the functional
      connectivity between two finger tapping tasks of ME and MI. Our results showed
      that using BC, the key node for the ME task mainly focused on the supplementary
      motor area, while the key node for the MI task mainly located in the right
      premotor area. These results characterized the connectivity patterns of ME and MI
      and may provide new insights into the neural mechanism underlying motor execution
      and imagination of movements. 

PMID- 24333972
TI  - Analytical approximations to inhomogeneously broadened, radiation damped free
      precession and echo signals.
AB  - The Dirac-Frenkel-Maclachlan (DFM) variation of parameters approach to
      approximately solving the time dependent Schrodinger equation is used to generate
      free precession and echo signals from the Bloch equations corrected for the
      effects of radiation damping and inhomogeneous broadening. Following a brief
      description of how the DFM method can be applied to the non-linear Bloch
      equations, two figures of merit designed to evaluate how a DFM optimized
      approximation compares with the exact solution is provided. This framework is
      used to optimize and evaluate the performance of six trial functions describing
      inhomogeneously broadened, radiation damped free precession and echo signals. The
      trial functions are then used to analyze the resolution enhancement and signal
      attenuation produced by pulse sequences that suppress radiation damping. 

PMID- 24333971
TI  - Epigenetics and the regulation of stress vulnerability and resilience.
AB  - The human brain has a remarkable capacity to adapt to and learn from a wide range
      of variations in the environment. However, environmental challenges can also
      precipitate psychiatric disorders in susceptible individuals. Why any given
      experience should induce one brain to adapt while another is edged toward
      psychopathology remains poorly understood. Like all aspects of psychological
      function, both nature (genetics) and nurture (life experience) sculpt the brain's
      response to stressful stimuli. Here we review how these two influences intersect
      at the epigenetic regulation of neuronal gene transcription, and we discuss how
      the regulation of genomic DNA methylation near key stress-response genes may
      influence psychological susceptibility or resilience to environmental stressors.
      Our goal is to offer a perspective on the epigenetics of stress responses that
      works to bridge the gap between the study of this molecular process in animal
      models and its potential usefulness for understanding stress vulnerabilities in
      humans. 

PMID- 24333973
TI  - Effect of ghrelin on chronic liver injury and fibrogenesis in male rats: possible
      role of nitric oxide.
AB  - Recent studies have revealed that ghrelin may be an antioxidant and anti
      inflammatory agent in many organs, however its role in chronic liver injury (CLI)
      remains unclear. The role of nitric oxide (NO) in CLI is controversial as
      evidence suggests that NO is either a primary mediator of liver cell injury or
      exhibits a protective effect against injurious stimuli. Recent evidence
      demonstrated that the therapeutic potential for ghrelin was through eNOS
      activation and increase in NO production. However, its role on NO production in
      the liver has not been previously investigated. The aim of this study was to
      investigate the role of ghrelin in treatment of CLI, and whether this action is
      mediated through NO. Forty male rats were divided into four groups: Group I:
      Control; Group II: chronic liver injury (CLI); Group III: CLI+Ghrelin; and Group
      IV: CLI+Ghrelin+l-NAME. Liver enzymes and tumor necrosis factor alpha (TNF
      alpha), were measured to assess hepatocellular injury. Liver tissue collagen
      content, malondialdehyde (MDA), gene expression of Bax, Bcl-2, and eNOS were
      assessed to determine the mechanism of ghrelin action. Results showed that
      ghrelin decreased serum liver enzymes and TNF-alpha levels. Ghrelin also reduced
      liver tissue collagen, MDA, and Bax gene expression, and increased Bcl-2 and eNOS
      gene expression. The effects on TNF-alpha, collagen, MDA, Bax, and eNOS were
      partially reversed in Group IV, suggesting that ghrelin's action could be through
      modulation of NO levels. Therefore, ghrelin's hepatoprotective effect is
      partially mediated by NO release. 

PMID- 24333974
TI  - [Ferenc Jakab -- greeting at 70th birthday].

PMID- 24333975
TI  - [Laparoscopic appendicectomy in 2013--a barely tolerated procedure turning into a
      gold standard operation?].
AB  - INTRODUCTION: Laparoscopic appendectomy is one of the first developed minimally
      invasive surgical procedures, nevertheless its judgement is contradictory up to
      the present day as far as its advantages and indications are concerned. METHODS:
      The authors of this article give an overview and analyse the relevant literature
      concerning laparoscopic appendectomy and the data of patients on whom
      appendectomy was performed from 01/01/2005 to 30/09/2013 with laparoscopic and
      open technique. RESULTS: At the Surgical Department of the Uzsoki Hospital 1214
      patients had appendectomy because of acute appendicitis from 01/01/2005 to
      30/09/2013. The applied surgical procedure was laparoscopy with 1065 patients
      (87.73%) and the open technique with 149 patients (12.27%). Since January 2006
      our main principle has been that in case of appendicitis the primary technique to
      be applied is laparoscopic appendectomy. We were forced to conversion with 16.5%
      of patients and as the operational experience of the department grows, the
      proportion of conversions tends to decrease. CONCLUSION: The advantages of
      laparoscopic appendectomy as opposed to open surgery have become obvious in the
      past decade, and the procedure may be recommended for all age groups. In case
      acute appendicitis is suspected the primary procedure to be applied in our
      department is the laparoscopic operation, the results of which are at least as
      good as that of open appendectomy. The routine application of laparoscopic
      appendectomy provides an excellent basis for the acquisition of advanced
      laparoscopic surgery thus appendectomy will not lose its training character due
      to the laparoscopic approach.

PMID- 24333976
TI  - [Evolution of sentinel lymph node biopsy in breast cancer--axillary staging in
      the past 15 years at the Uzsoki Street Hospital].
AB  - INTRODUCTION: Sentinel biopsy technique was performed in Europe in 1996.It was a
      great improvement in the surgical treatment of breast cancer, it decreased the
      number of patients suffering from early and late morbidity following axillary
      lymph node dissection (ALND). In our paper we demonstrate the evolution of
      sentinel biopsy technique (SLNB), as well as the changes in our policy on
      axillary treatment in line with the European trends. METHODS: The authors of this
      article give an overview and analyse the relevant literature concerning sentinel
      lymph node biopsy and data of patients on whom sentinel lymph node biopsy was
      performed from 01/01/2001 to 31/12/2012. RESULTS: Between 2001 and 2013 we
      performed 3756 breast operations, 2742 of those were done for malignant disease.
      Altogether we performed 744 sentinel lymph node biopsies in the Uzsoki teaching
      Hospital. The proportion of SLNB patients is increasing, it was 24.6% between
      2001-2006 and 29.2% between 2007-2012, respectively. The indication of SLNB is
      widening, there might be justification of the technique even by multifocal or
      multilocular disease, in male patients, after former breats surgery or even in
      pregnant patients. CONCLUSION: Histological examination of sentinel lymph node
      and its effect on complex treatment of breats cancer may place the role of
      surgical axillary staging in a brand new aspect in the near future perhaps.

PMID- 24333977
TI  - [Preoperative chemotherapy in the surgical treatment of colorectal liver
      metastases].
AB  - INTRODUCTION: The only curative treatment of colorectal liver metastases (CRLM)
      is surgical resection. Preoperative/neoadjuvant chemotherapy can be used for
      resectable, for borderline resectable or even for irresectable CRLM patients.
      PATIENTS: Data of CRLM patients treated with surgical resection at the Uzsoki
      Hospital were analysed. Patients were classified into two groups, (A) who
      received preoperative chemotherapy before hepatic resection, and (B) who received
      no chemotherapy before resection. RESULTS: Between 01.01.2007. and 31.12.2010.
      128 CRLM patients were treated with hepatic resection. 68 patients (53%) received
      chemotherapy before hepatic resection, 60 patients (47%) were resected without
      neoadjuvant chemotherapy. There was no significant difference in the
      complications between the groups (p = 0.39). Median overall survival was 41
      months. The progression free survival (PFS) at 3 and 5 years were 25%, the 3 and
      5 year overall survival (OS) were 55% and 31%. Both PFS and OS were significantly
      worse in the chemotherapy group (p = 0.014, p = 0.015). The subgroup of patients
      receiving bevacizumab containing preoperative chemotherapy has significanly
      better PFS than patients receiving only cytotoxic chemotherapy (p = 0.004).
      CONCLUSION: Surgical resection of CRLM patients results good survival data even
      in non-selected patients, although the very long survival results reported in the
      literature couldn't have been reproduced in this patient population. When
      preoperative chemotherapy was combined with bevacizumab, survival was similar to
      the upfront resected patients.

PMID- 24333978
TI  - [Evaluation of thrombocytosis as predictive factor in colorectal cancer].
AB  - INTRODUCTION/AIM OF THE STUDY: Preoperative thrombocytosis proved to be a
      negative prognostic factor in several solid tumor. However, there is still debate
      in the literature regarding colorectal cancer. The aim of our study was to
      examine whether thrombocytosis is an independent risk factor for metastasis
      development and predictor of survival in colorectal cancer. MATERIALS AND
      METHODS: Clinicopathological data of 336 patients with colorectal cancer (CRC)
      and 118 patients with liver metastasis of colorectal cancer (mCRC) who had
      operation between 2001 and 2011 were collected retrospectively. Thrombocytosis
      was defined as 400 G/L < platelet count. Disease-free survival (DFS) and overall
      survival (OS) were determined with Kaplan-Meier method supported by log-rank
      test. RESULTS: Both in the CRC and the mCRC group OS was significantly shorter in
      patients who had elevated platelet count (HR = 2.2, p < 0.001 and HR = 2.9, p =
      0.018, respectively). Multivariate analysis confirmed that elevated platelet
      count was an independent prognostic factor of both CRC (HR = 1.7, p = 0.035) and
      mCRC (HR = 3.1, p = 0.017). DFS was significantly shorter in patients with
      elevated platelet count in the CRC group (HR = 2.0, p = 0.011). DISCUSSION: The
      platelet count is a valuable and cheap prognostic marker for the prediction of
      survival in patients both with CRC and mCRC.

PMID- 24333979
TI  - [Long-term survival after lung-sparing central bronchoplastic procedures [CBPs]
      for malignant tumors].
AB  - BACKGROUND: Bronchial malignancies are leading tumour-related cause of death.
      Prolonged survival can only be expected after radical resections. Central
      bronchoplastic procedures, which save the whole lung parenchyma, however, may
      play a role. AIM: These bronchoplastic procedures can be good alternatives for
      pulmonectomies. The value of these operations can be evaluated by postoperative
      mortality complication, and the survival rate. MATERIAL AND METHODS: In the
      period of 1985-2012 we operated 7130 bronchial carcinomas. Of these, 7 cases of
      80 central broncoplastics we preserved the whole lung (in one case as an
      alternative for inoperability, in 6 patients as an option instead of
      pulmonectomy). The indications were carcinoid in four cases, epidermoid
      carcinoma, mucoepidermoid carcinoma and main carina SCLC after induction chemo
      radiotherapy. The average age of the 4 male and of the 3 female patients were
      28.5 (14-58) years. In 5 cases the right main bronchus, while in one case the
      left main bronchus was resected and the bronchial tree was reconstructed. In one
      case (SCLC patient) we made a complete carina resection and end-to-end
      anastomosis between the trachea and the rebuilt neocarina to preserve both lungs.
      The anastomosis was made with 3-4/0 PDS interrupted sutures above a sterile tube
      (6 cases) and in one case due to a jet catheter which were positioned through the
      operation field into the distal part of the main healthy bronchus. RESULTS: There
      was no operative mortality nor bronchopleural fistula. In the early postoperative
      period we applied repeated bronchoscopic suctions. In the patient with carina
      SCLC anastomosis stenosis developed. The main bronchi were temporarily stented.
      This patient is fit 174 months after the intervention, the Karnofsky index
      mesures to 90%. Other 5 patients are alive without any consequences of recurrence
      nor metastasis. The patient with epidermoid carcinoma died 83 months later
      because of distant metastases of a SCLC, originating from the contralateral lung.
      The mean survival is 118 (7-233) months. CONCLUSION: In case of some properly
      selected localised mainstem bronchial malignancies, such as young age and low
      grade malignancy, radical surgical interventions can be performed with long term
      survival preserving the whole lung due to special CBPs. Some such successful
      series and case reports (under 200 cases) can be found in the literature but the
      long-term survival data was not demonstrated in most publications. In Hungary
      there has not been any publications yet on such a successful series with long
      term survival. These results are remarkable within international standards.

PMID- 24333980
TI  - [Pancreatojejunostomy--with purse-string suture].
AB  - INTRODUCTION: Pancreatic fistula is one of the most relevant complications
      following pancreatoduodenectomies. Significant effort has been made to decrease
      it. The aim of the authors was to show a pancreatojejunal anastomosis combined
      with purse-string suture, and report the first experiences, as well. MATERIAL AND
      METHODS: The implantation pancreatojejunostomy - which has been applied by the
      authors since 2003 - was modified, that the remnant of the pancreas was fixed in
      the jejunum with one purse-string and two mattress sutures. In case of a soft
      pancreas the Wirsungian duct was stented, then the vein canule was pulled out to
      the outside throught the afferent jejunal limb. The method was applied in seven
      patients during pylorus-preserving pancreatoduodenectomy performed for neoplasm.
      RESULTS: In the postoperative period there were two complications in two patients
      noted (a bleeding ulcer developed in the region of the duodenojejunostomy and a
      transient confusion). However there was no pancreatic fistula, reoperation or
      early mortality detected. CONCLUSIONS: While major conclusions can not be drawn
      due to the relatively small number of cases, this method seems promising and it
      is worth to carry out further trials.

PMID- 24333981
TI  - [The frequency of bacteria in human gallstones].
AB  - INTRODUCTION: Complications caused by lost gallstones within the abdominal cavity
      are well known. Abscesses, perforation of the gastro-intestinal tract were all
      described in the literature, but gallstones were found in hernial sac, or even in
      sputum after it penetrated through the diaphragm into the respiratory tract.
      These complications can develop between several weeks to several years
      postoperatively. Most complications can be treated surgically only. MATERIALS AND
      METHODS: Fifty gallstones and bile samples were collected from 50 patients who
      underwent cholecystectomy (36 female / 14 male, avarge age: 60.8 +/- 6.8 years).
      All samples were sent for microbiological examination. RESULTS: bacterial
      colonization of the gallstone and the bile were found in 16 cases. Four of them
      showed acute inflammation in the gallbladder while pathological signs of chronic
      inflammation in the gallbladder wall were detected in eight cases. Empyema was
      found in four cases. Bacteria from enteral origin (Esherichia coli, Enterococcus
      faecalis, Enterobacter cloacae) was detected in 13 cases, while non-enteral
      (Klebsiella penumoniae, Streptococcus alfa-haemoliticus) colony were detected in
      three cases. Positive bacterial cultures were identified in twelve female and
      fourmale patients. CONCLUSIONS: Different types of bacteria can be found in the
      gallstones, which may cause various complications.

PMID- 24333986
TI  - The survival time of chocolates on hospital wards: covert observational study.
AB  - OBJECTIVE: To quantify the consumption of chocolates in a hospital ward
      environment. DESIGN: Multicentre, prospective, covert observational study.
      SETTING: Four wards at three hospitals (where the authors worked) within the
      United Kingdom. PARTICIPANTS: Boxes of Quality Street (Nestle) and Roses
      (Cadbury) on the ward and anyone eating these chocolates. INTERVENTION: Observers
      covertly placed two 350 g boxes of Quality Street and Roses chocolates on each
      ward (eight boxes were used in the study containing a total of 258 individual
      chocolates). These boxes were kept under continuous covert surveillance, with the
      time recorded when each chocolate was eaten. MAIN OUTCOME MEASURE: Median
      survival time of a chocolate. RESULTS: 191 out of 258 (74%) chocolates were
      observed being eaten. The mean total observation period was 254 minutes (95%
      confidence interval 179 to 329). The median survival time of a chocolate was 51
      minutes (39 to 63). The model of chocolate consumption was non-linear, with an
      initial rapid rate of consumption that slowed with time. An exponential decay
      model best fitted these findings (model R(2)=0.844, P<0.001), with a survival
      half life (time taken for 50% of the chocolates to be eaten) of 99 minutes. The
      mean time taken to open a box of chocolates from first appearance on the ward was
      12 minutes (95% confidence interval 0 to 24). Quality Street chocolates survived
      longer than Roses chocolates (hazard ratio for survival of Roses v Quality Street
      0.70, 95% confidence interval 0.53 to 0.93, P=0.014). The highest percentages of
      chocolates were consumed by healthcare assistants (28%) and nurses (28%),
      followed by doctors (15%). CONCLUSIONS: From our observational study, chocolate
      survival in a hospital ward was relatively short, and was modelled well by an
      exponential decay model. Roses chocolates were preferentially consumed to Quality
      Street chocolates in a ward setting. Chocolates were consumed primarily by
      healthcare assistants and nurses, followed by doctors. Further practical studies
      are needed.

PMID- 24333987
TI  - Alkaline pH activates the transport activity of GLUT1 in L929 fibroblast cells.
AB  - The widely expressed mammalian glucose transporter, GLUT1, can be acutely
      activated in L929 fibroblast cells by a variety of conditions, including glucose
      deprivation, or treatment with various respiration inhibitors. Known thiol
      reactive compounds including phenylarsine oxide and nitroxyl are the fastest
      acting stimulators of glucose uptake, implicating cysteine biochemistry as
      critical to the acute activation of GLUT1. In this study, we report that in L929
      cells glucose uptake increases 6-fold as the pH of the uptake solution is
      increased from 6 to 9 with the half-maximal activation at pH 7.5; consistent with
      the pKa of cysteine residues. This pH effect is essentially blocked by the
      pretreatment of the cells with either iodoacetamide or cinnamaldehyde, compounds
      that form covalent adducts with reduced cysteine residues. In addition, the
      activation by alkaline pH is not additive at pH 8 with known thiol reactive
      activators such as phenylarsine oxide or hydroxylamine. Kinetic analysis in L929
      cells at pH 7 and 8 indicate that alkaline conditions both increases the Vmax and
      decreases the Km of transport. This is consistent with the observation that pH
      activation is additive to methylene blue, which activates uptake by increasing
      the Vmax, as well as to berberine, which activates uptake by decreasing the Km.
      This suggests that cysteine biochemistry is utilized in both methylene blue and
      berberine activation of glucose uptake. In contrast a pH increase from 7 to 8 in
      HCLE cells does not further activate glucose uptake. HCLE cells have a 25-fold
      higher basal glucose uptake rate than L929 cells and the lack of a pH effect
      suggests that the cysteine biochemistry has already occurred in HCLE cells. The
      data are consistent with pH having a complex mechanism of action, but one likely
      mediated by cysteine biochemistry. 

PMID- 24333988
TI  - Sub-NOAEL amounts of vinclozolin and xenoestrogens target rat chondrogenesis in
      vivo.
AB  - Several endocrine disrupting compounds (EDC) elicit skeletal dysgenesis at
      pharmacological doses. We have investigated the impact of doses below the "No
      Observed Adverse Effect" (NOAEL) for vinclozolin (V), an anti-androgenic
      fungicide, alone or associated with xenoestrogens (Genistein, G and bisphenol-A,
      BPA). V, G, BPA and their combinations were administered orally to female Wistar
      rats during gestation and lactation. F1 and F2 offspring were investigated for
      skeletal anomalies at post-natal days 30, 110 (d30, d110). Skeletal development
      was monitored by measuring caudal vertebrae and long bones dimensions by X-ray
      micro-CT-scan. A significant increase in Inter Transverse Apophysis (ITA)
      distance at the upper head of caudal vertebrae, associated with a reduction in
      vertebral body height was observed in treated F1 females, but not males.
      Histometrical analysis of vertebral body growth plate cartilage was performed on
      serial sections of caudal vertebrae. F1 females but not males showed a diminution
      in growth plate thickness, with greater impact on the hypertrophic zone. All
      effects were maximal at d30. Effects on ITA width persisted until d110 while
      effects on growth plate disappeared. These effects were essentially vinclozolin
      or BPA-dependent. F2 animals were not affected. Our data suggest that vinclozolin
      and xenoestrogens act as cartilage developmental disruptors. We suggest that
      present NOAEL values for these compounds, and EDC at large, might be reconsidered
      using gestational exposure models. Finally, micro CT-scan appears a valuable non
      invasive technique to detect EDC effects on live fauna. 

PMID- 24333989
TI  - Biochemical and mutational studies of allantoinase from Bacillus licheniformis
      CECT 20T.
AB  - Allantoinases (allantoin amidohydrolase, E.C. 3.5.2.5) catalyze the hydrolysis of
      the amide bond of allantoin to form allantoic acid, in those organisms where
      allantoin is not the final product of uric acid degradation. Despite their
      importance in the purine catabolic pathway, sequences of microbial allantoinases
      with proven activity are scarce, and only the enzyme from Escherichia coli
      (AllEco) has been studied in detail in the genomic era. In this work, we report
      the cloning, purification and characterization of the recombinant allantoinase
      from Bacillus licheniformis CECT 20T (AllBali). The enzyme was a homotetramer
      with an apparent Tm of 62 +/- 1  degrees C. Optimal parameters for the enzyme
      activity were pH 7.5 and 50  degrees C, showing apparent Km and kcat values of
      17.7 +/- 2.7 mM and 24.4 +/- 1.5 s(-1), respectively. Co(2+) proved to be the
      most effective cofactor, inverting the enantioselectivity of AllBali when
      compared to that previously reported for other allantoinases. The common ability
      of different cyclic amidohydrolases to hydrolyze distinct substrates to the
      natural one also proved true for AllBali. The enzyme was able to hydrolyze
      hydantoin, dihydrouracil and 5-ethyl-hydantoin, although at relative rates 3-4
      orders of magnitude lower than with allantoin. Mutagenesis experiments suggest
      that S292 is likely implicated in the binding of the allantoin ring through the
      carbonyl group of the polypeptide main chain, which is the common mechanism
      observed in other members of the amidohydrolase family. In addition, our results
      suggest an allosteric effect of H2O2 toward allantoinase. 

PMID- 24333990
TI  - Nanopesticide research: current trends and future priorities.
AB  - The rapid developments in nanopesticide research over the last two years have
      motivated a number of international organizations to consider potential issues
      relating to the use of nanotechnology for crop protection. This analysis of the
      latest research trends provides a useful basis for identifying research gaps and
      future priorities. Polymer-based formulations have received the greatest
      attention over the last two years, followed by formulations containing inorganic
      nanoparticles (e.g., silica, titanium dioxide) and nanoemulsions. Investigations
      have addressed the lack of information on the efficacy of nanopesticides and a
      number of products have been demonstrated to have greater efficacy than their
      commercial counterparts. However, the mechanisms involved remain largely unknown
      and further research is required before any generalizations can be made. There is
      now increased motivation to develop nanopesticides that are less harmful to the
      environment than conventional formulations, and future investigations will need
      to assess whether any promising products developed are able to compete with
      existing formulations, in terms of both cost and performance. Investigations into
      the environmental fate of nanopesticides remain scarce, and the current state of
      knowledge does not appear to be sufficient for a reliable assessment to be made
      of their associated benefits and risks. A great deal of research will therefore
      be required over the coming years, and will need to include (i) the development
      of experimental protocols to generate reliable fate properties, (ii)
      investigations into the bioavailability and durability of nanopesticides, and
      (iii) evaluation of current environmental risk assessment approaches, and their
      refinement where appropriate. 

PMID- 24333991
TI  - Modeling and analysis of personal exposures to VOC mixtures using copulas.
AB  - Environmental exposures typically involve mixtures of pollutants, which must be
      understood to evaluate cumulative risks, that is, the likelihood of adverse
      health effects arising from two or more chemicals. This study uses several
      powerful techniques to characterize dependency structures of mixture components
      in personal exposure measurements of volatile organic compounds (VOCs) with aims
      of advancing the understanding of environmental mixtures, improving the ability
      to model mixture components in a statistically valid manner, and demonstrating
      broadly applicable techniques. We first describe characteristics of mixtures and
      introduce several terms, including the mixture fraction which represents a
      mixture component's share of the total concentration of the mixture. Next, using
      VOC exposure data collected in the Relationship of Indoor Outdoor and Personal
      Air (RIOPA) study, mixtures are identified using positive matrix factorization
      (PMF) and by toxicological mode of action. Dependency structures of mixture
      components are examined using mixture fractions and modeled using copulas, which
      address dependencies of multiple variables across the entire distribution. Five
      candidate copulas (Gaussian, t, Gumbel, Clayton, and Frank) are evaluated, and
      the performance of fitted models was evaluated using simulation and mixture
      fractions. Cumulative cancer risks are calculated for mixtures, and results from
      copulas and multivariate lognormal models are compared to risks calculated using
      the observed data. Results obtained using the RIOPA dataset showed four VOC
      mixtures, representing gasoline vapor, vehicle exhaust, chlorinated solvents and
      disinfection by-products, and cleaning products and odorants. Often, a single
      compound dominated the mixture, however, mixture fractions were generally
      heterogeneous in that the VOC composition of the mixture changed with
      concentration. Three mixtures were identified by mode of action, representing
      VOCs associated with hematopoietic, liver and renal tumors. Estimated lifetime
      cumulative cancer risks exceeded 10(-3) for about 10% of RIOPA participants.
      Factors affecting the likelihood of high concentration mixtures included city,
      participant ethnicity, and house air exchange rates. The dependency structures of
      the VOC mixtures fitted Gumbel (two mixtures) and t (four mixtures) copulas,
      types that emphasize tail dependencies. Significantly, the copulas reproduced
      both risk predictions and exposure fractions with a high degree of accuracy, and
      performed better than multivariate lognormal distributions. Copulas may be the
      method of choice for VOC mixtures, particularly for the highest exposures or
      extreme events, cases that poorly fit lognormal distributions and that represent
      the greatest risks. 

PMID- 24333992
TI  - Environmental and ecological impacts of water supplement schemes in a heavily
      polluted estuary.
AB  - Water supplement has been used to improve water quality in a heavily polluted
      river with small base flow. However, its adverse impacts particularly on nearby
      sensitive ecosystems have not been fully investigated in previous studies. In
      this paper, using the Shenzhen River estuary in China as a case study, the
      impacts of two potential water supplement schemes (reclaimed water scheme and
      seawater scheme) on water quality improvement and salinity alteration of the
      estuary are studied. The influences of salinity alteration on the dominant
      mangrove species (Aegiceras corniculatum, Kandelia candel, and Avicennia marina)
      are further evaluated by comparing the alteration with the historical salinity
      data and the optimum salinity range for mangrove growth. The results obtained
      indicate that the targets of water quality improvement can be achieved by
      implementing the water supplement schemes with roughly the same flow rates. The
      salinity under the reclaimed water scheme lies in the range of historical
      salinity variation, and its average value is close to the optimum salinity for
      mangrove growth. Under the seawater scheme, however, the salinity in the estuary
      exceeds the range of historical salinity variation and approaches to the upper
      bound of the survival salinity of the mangrove species which have a relatively
      low salt tolerance (e.g. A. corniculatum). Therefore, the seawater scheme has
      negative ecological consequences, while the reclaimed water scheme has less
      ecological impact and is recommended in this study. 

PMID- 24333993
TI  - Economic valuation of domestic water uses.
AB  - There are many reasons of concern about the quality of water for domestic uses.
      The strategic goals of water tariffs must include savings, efficient management
      and equity in order to optimise availability of the best quality water. The main
      domestic uses of water are food preparation, personal hygiene and household
      cleaning; not all of them need the same quality, and for some of them there are
      even potential substitutes. In order to contribute to this debate, we need to
      know how these different uses are valued by direct users. This article focuses on
      eliciting values for different domestic uses, using discrete choice experiments.
      As far as we know, this is the first time that a differentiated valuation per use
      has been defined. The paper introduces three innovations in the design of the
      experiment. The design takes into account decisive variables in household water
      consumption, such as family size, together with the consumption level, and the
      options offered in the choice task are combinations of different prices for each
      of the uses. A latent class model with both common and class-specific random
      parameters is applied to better account for the influence of heterogeneity in the
      respondents' choices. The results show that the most valued use depends on the
      consumption level class. 

PMID- 24333994
TI  - Methane and nitrous oxide emissions from a subtropical estuary (the Brisbane
      River estuary, Australia).
AB  - Methane (CH4) and nitrous oxide (N2O) are two key greenhouse gases. Their global
      atmospheric budgeting is, however, flout with challenges partly due to lack of
      adequate field studies determining the source strengths. Knowledge and data
      limitations exist for subtropical and tropical regions especially in the southern
      latitudes. Surface water methane and nitrous oxide concentrations were measured
      in a subtropical estuarine system in the southern latitudes in an extensive field
      study from 2010 to 2012 and water-air fluxes estimated using models considering
      the effects of both wind and flow induced turbulence. The estuary was found to be
      a strong net source of both CH4 and N2O all-year-round. Dissolved N2O
      concentrations ranged between 9.1 +/- 0.4 to 45.3 +/- 1.3 nM or 135 to 435% of
      atmospheric saturation level, while CH4 concentrations varied between 31.1 +/-
      3.7 to 578.4 +/- 58.8 nM or 1210 to 26,430% of atmospheric saturation level.
      These results compare well with measurements from tropical estuarine systems.
      There was strong spatial variability with both CH4 and N2O concentrations
      increasing upstream the estuary. Strong temporal variability was also observed
      but there were no clear seasonal patterns. The degree of N2O saturation
      significantly increased with NOx concentrations (r(2)=0.55). The estimated water
      air fluxes varied between 0.1 and 3.4 mg N2O m(-2)d(-1) and 0.3 to 27.9 mg CH4 m(
      2)d(-1). Total emissions (CO2-e) were N2O (64%) dominated, highlighting the need
      for reduced nitrogen inputs into the estuary. Choice of the model(s) for
      estimation of the gas transfer velocity had a big bearing on the estimated total
      emissions.

PMID- 24333996
TI  - Levels of brominated flame retardants (BFRs) in honey samples from different
      geographic regions.
AB  - Concentrations of 17 brominated flame retardants (BFRs), including two "novel"
      BFRs (1,2-bis(2,4,6-tribromophenoxy)ethane, BTBPE and decabromodiphenylethane,
      DBDPE), have been determined to be in 35 commercial honey samples from Brazil,
      Spain, Portugal, Slovenia and Morocco. The results revealed the presence of low
      amounts (between<LOD to 24.7 pg g(-1) fresh weight) of individual BFRs. The
      highest total BFR concentrations were found in Brazilian honeys (mean of 5.19,
      range of 0.46-25.2 pg g(-1) f.w.), followed by Moroccan (mean of 4.40, range of
      2.49-8.0 pg g(-1) f.w.), Portuguese (mean of 2.24, range of 1.33-3.81 pg g(-1)
      f.w.), Spanish (mean of 1.77, range of 0.49-2.96 pg g(-1) f.w.), and Slovenian
      (mean of 0.93, range of 0.75-1.09 pg g(-1) f.w.) honey samples. The most
      remarkable findings in this study were the large contribution of the low
      brominated PBDEs, principally BDE-47, found in honey samples from Slovenia, Spain
      and Portugal. Meanwhile the most abundant BFRs found in Brazilian and Moroccan
      honeys were the two novel BFRs (BTBPE and DBDPE). The detection of BFRs in honeys
      from different countries highlights the risk that their presence poses to the
      health of humans and wildlife since honey is a non-fatty natural product that is
      highly consumed all over the world.

PMID- 24333995
TI  - Hair mercury and urinary cadmium levels in Belgian children and their mothers
      within the framework of the COPHES/DEMOCOPHES projects.
AB  - A harmonized human biomonitoring pilot study was set up within the frame of the
      European projects DEMOCOPHES and COPHES. In 17 European countries, biomarkers of
      some environmental pollutants, including urinary cadmium and hair mercury, were
      measured in children and their mothers in order to obtain European-wide
      comparison values on these chemicals. The Belgian participant population
      consisted in 129 school children (6-11 years) and their mothers (<= 45 years)
      living in urban or rural areas of Belgium. The geometric mean levels for mercury
      in hair were 0.383 MUg/g and 0.204 MUg/g for respectively mothers and children.
      Cadmium in mother's and children's urine was detected at a geometric mean
      concentration of respectively 0.21 and 0.04 MUg/l. For both biomarkers, levels
      measured in the mothers and their child were correlated. While the urinary
      cadmium levels increased with age, no trend was found for hair mercury content,
      except the fact that mothers hold higher levels than children. The hair mercury
      content increased significantly with the number of dental amalgam fillings,
      explaining partially the higher levels in the mothers by their higher presence
      rate of these amalgams compared to children. Fish or seafood consumption was the
      other main parameter determining the mercury levels in hair. No relationship was
      found between smoking status and cadmium or mercury levels, but the studied
      population included very few smokers. Urinary cadmium levels were higher in both
      mothers and children living in urban areas, while for mercury this difference was
      only significant for children. Our small population showed urinary cadmium and
      hair mercury levels lower than the health based guidelines suggested by the WHO
      or the JECFA (Joint FAO/WHO Expert Committee on Food Additives). Only 1% had
      cadmium level slightly higher than the German HBM-I value (1 MUg/l for adults),
      and 9% exceeded the 1 MUg mercury/g hair suggested by the US EPA.

PMID- 24333997
TI  - Response of bacterial communities to environmental changes in a mesoscale
      subtropical watershed, Southeast China.
AB  - This study used 16S rRNA gene-based pyrosequencing (16S-pyrotag) to investigate
      both planktonic and benthic bacterial communities in two main tributaries (North
      River and West River) of the Jiulong River Watershed (JRW), a mesoscale
      subtropical watershed that has experienced intensive human perturbation in recent
      decades. The results of 16S-pyrotag showed that benthic bacterial communities
      were clearly more diverse and uniform than surface bacterioplankton communities.
      The results of taxonomic assignments indicated that Betaproteobacteria,
      Actinobacteria and Firmicutes were significantly more abundant in planktonic than
      in benthic communities, whereas the relative abundances of Acidobacteria, Delta-,
      Gammaproteobacteria, Chloroflexi and Nitrospira were higher in sediment than in
      water samples. In particular, several sewer- and fecal-pollution bacterial
      indicators were observed in water samples, implying that the water bodies of the
      JRW were contaminated by fecal pollution. Using the typical freshwater bacteria
      (TFB) taxonomic framework, 57.6 +/- 10%, 27.6 +/- 10.9% and 10.4 +/- 6.9% of
      sequences recovered from planktonic communities could be assigned to lineages,
      clades and tribes of TFB, respectively. The relatively lower abundance of TFB
      implied that some unknown or unique autochthonous bacterioplankton populations
      occurred in the JRW. The principal coordinate analysis (PCoA) and one way
      analysis of similarity (ANOSIM) analysis demonstrated that planktonic bacterial
      community structures were significantly different between North River and West
      River, whereas benthic communities from these two tributaries were grouped
      together. Multivariate statistical analysis revealed that nutrient concentrations
      and stoichiometry were the key drivers of both alpha- and beta-diversity patterns
      of bacterioplankton communities. Overall, our results indicate that the
      diversity, composition and structure of planktonic bacterial communities are
      sensitive to water chemistry (e.g., nutrient concentrations and stoichiometry) in
      the JRW, and therefore can serve as a good sentinel of environmental changes in
      this watershed.

PMID- 24333998
TI  - Occurrence of human enteric viruses at freshwater beaches during swimming season
      and its link to water inflow.
AB  - Human enteric viruses are significant etiological agents for many recreational
      waterborne illnesses. The occurrence and density of human enteric viruses such as
      human adenovirus (HAdV), human enterovirus (HEnV), and human norovirus genogroups
      I/II (HNoV GI/GII) were investigated using quantitative real-time PCR (qPCR) at
      freshwater beaches along with monitoring fecal indicators and environmental
      parameters. During the 2009 swimming season, water samples were collected from
      three inland freshwater beaches in Ohio, USA. Of the total samples, 40% (26/65)
      and 17% (11/65) were positive for HAdV and HEnV respectively, but HNoV GI/GII
      were not detected. There was no significant association among the detected human
      enteric viruses (HAdV and HEnV) and fecal bacteria indicators (Escherichia coli
      and Bacteroides) by Spearman correlation and principal component analyses.
      Logistic regression analysis also revealed that the odds of finding HAdV or HEnV
      was not influenced by levels of fecal bacteria indicators. However, there was a
      14-fold increase in the odds of HEnV detection for each 1-log increase in daily
      water inflow (m(3)/s) into freshwater beach reservoirs (adjusted odds ratio=14.2;
      95% confidence interval=1.19-171). In summary, the viral occurrence at the
      freshwater beaches was not readily explained by the levels of fecal bacteria
      indicators, but appeared to be more related to water reservoir inflows. These
      results suggest that hydrological data must be considered in future epidemiology
      efforts aimed at characterizing beach water safety. 

PMID- 24333999
TI  - Persistence of oxyfluorfen in soil, runoff water, sediment and plants of a
      sunflower cultivation.
AB  - A field dissipation and transport study of oxyfluorfen in a sunflower cultivation
      under Mediterranean conditions have been conducted in silty clay plots
      (cultivated and uncultivated) with two surface slopes (1% and 5%). The soil
      dissipation and transport of oxyfluorfen in runoff water and sediment, as well as
      the uptake by sunflower plants, were investigated over a period of 191 days.
      Among different kinetic models assayed, soil dissipation rate of oxyfluorfen was
      better described by first-order kinetics. The average half-life was 45 and 45.5
      days in cultivated plots with soil slopes 5% and 1% respectively, and 50.9 and
      52.9 days in uncultivated plots with soil slopes 5% and 1%. The herbicide was
      detected below the 10 cm soil layer 45 days after application (DAA). Limited
      amounts of oxyfluorfen were moved with runoff water and the cumulative losses
      from tilled and untilled plots with slope 5% were estimated at 0.007% and 0.005%
      of the initial applied active ingredient, while for the plots with slope of 1%,
      the respective values were 0.002% and 0.001%. The maximum concentration of
      oxyfluorfen in sediment ranged from 1.46 MUg g(-1) in cultivated plot with soil
      slope 1% to 2.33 MUg g(-1) in uncultivated plot with soil slope 5%. The
      cumulative losses from tilled and untilled plots with slope 5% were estimated at
      0.217% and 0.170% while for the plots with slope of 1%, the respective values
      were 0.055% and 0.025%. Oxyfluorfen was detected in sunflower plants until the
      day of harvest; maximum concentrations in stems and leaves (0.042 MUg g(-1)) were
      observed 33 DAA and in roots (0.025 MUg g(-1)) 36 DAA. In conclusion, oxyfluorfen
      hardly moves into silty clay soil and exhibited low run-off potential so it
      represents a low risk herbicide for the contamination of ground and adjacent
      water resources.

PMID- 24334000
TI  - Fire severity, residuals and soil legacies affect regeneration of Scots pine in
      the Southern Alps.
AB  - Regeneration of non fire-adapted conifers following crown fires on the European
      Alps is often delayed or unsuccessful. Fire may limit establishment by
      eliminating seed trees, altering soil properties, or modifying microsite and soil
      conditions via disturbance legacies. However, the effect of soil legacies on post
      fire establishment has rarely been discussed. We analyzed the abundance of Scots
      pine regeneration in a 257 ha wildfire in an inner-alpine forest. Our aims were
      (1) to model fire intensity at the soil surface and topsoil heating along a
      gradient of increasing fire severities; (2) to assess the differences in soil
      properties along the fire severity gradient; (3) to model the effect of
      disturbance and soil legacies on the density of pine seedlings. We reconstructed
      fire behavior and soil heating with the First Order Fire Effects Model (FOFEM),
      tested the effect of fire severity on soils by nonparametric distributional
      tests, and modeled seedling density as a function of site, disturbance and soil
      legacies by fitting a GLM following a variable selection procedure. Topsoil
      heating differed markedly between the moderate and high severity fires, reaching
      temperatures high enough to strongly and permanently alter soil properties only
      in the latter. High fire severity resulted in decreased soil consistency and wet
      aggregate stability. Burned soils had lower organic matter and cations than those
      unburned. Pine seedlings favored low-fertility, eroded, and chemically poor
      sites. Establishment was facilitated by the presence of coarse woody debris, but
      hampered by increasing distance from the seed source. These results suggest that
      in dry, inner-alpine valleys, fire residuals and soil legacies interact in
      determining the success of Scots pine re-establishment. High severity fire can
      promote favorable soil conditions, but distance from the seed source and high
      evaporation rates of bare soils must be mitigated in order to ensure a successful
      restoration.

PMID- 24334001
TI  - Organic micropollutants in the Yangtze River: seasonal occurrence and annual
      loads.
AB  - Twenty percent of the water run-off from China's land surface drains into the
      Yangtze River and carries the sewage of approximately 400 million people out to
      sea. The lower stretch of the Yangtze therefore offers the opportunity to assess
      the pollutant discharge of a huge population. To establish a comprehensive
      assessment of micropollutants, river water samples were collected monthly from
      May 2009 to June 2010 along a cross-section at the lowermost hydrological station
      of the Yangtze River not influenced by the tide (Datong Station, Anhui province).
      Following a prescreening of 268 target compounds, we examined the occurrence,
      seasonal variation, and annual loads of 117 organic micropollutants, including 51
      pesticides, 43 pharmaceuticals, 7 household and industrial chemicals, and 16
      polycyclic aromatic hydrocarbons (PAHs). During the 14-month study, the maximum
      concentrations of particulate PAHs (1-5 MUg/g), pesticides (11-284 ng/L),
      pharmaceuticals (5-224 ng/L), and household and industrial chemicals (4-430 ng/L)
      were generally lower than in other Chinese rivers due to the dilution caused of
      the Yangtze River's average water discharge of approximately 30,000 m(3)/s. The
      loads of most pesticides, anti-infectives, and PAHs were higher in the wet season
      compared to the dry season, which was attributed to the increased agricultural
      application of chemicals in the summer, an elevated water discharge through the
      sewer systems and wastewater treatment plants (WWTP) as a result of high
      hydraulic loads and the related lower treatment efficiency, and seasonally
      increased deposition from the atmosphere and runoff from the catchment. The
      estimated annual load of PAHs in the river accounted for some 4% of the total
      emission of PAHs in the whole Yangtze Basin. Furthermore, by using sucralose as a
      tracer for domestic wastewater, we estimate a daily disposal of approximately 47
      million m(3) of sewage into the river, corresponding to 1.8% of its average
      hydraulic load. In summary, the annual amounts flushed by the Yangtze River into
      the East China Sea were 2.9*10(6)tons of dissolved and particulate organic carbon
      (DOC and POC), 369 tons of PAHs, 98 tons of pesticides, 152 tons of
      pharmaceuticals, and 273 tons of household and industrial chemicals. While the
      concentrations seem comparably moderate, the pollutant loads are considerable and
      pose an increasing burden to the health of the marine coastal ecosystem.

PMID- 24334002
TI  - Caffeine supplementation modulates oxidative stress markers in the liver of
      trained rats.
AB  - AIMS: Caffeine has been widely used in sports competitions due to its ergogenic
      effects. Most of the studies regarding caffeine and exercise have focused on
      muscle and plasma adaptations, while the impact on the liver is scarcely
      described. The aim is to analyze the effects of caffeine and exercise training on
      oxidative stress markers and injury-related parameters in the liver. MAIN
      METHODS: Rats were divided into sedentary/saline, sedentary/caffeine,
      exercise/saline, and exercise/caffeine groups. Exercise groups underwent 4 weeks
      of swimming training, and caffeine (6 mg/kg, p.o.) was supplemented throughout
      the training protocol. Injury-related liver parameters were assessed in plasma,
      while redox status and oxidative stress markers were measured on liver
      homogenates. KEY FINDINGS: Exercise training increased muscle citrate synthase
      activity in the muscle, while in caffeine decreased its activity in both
      sedentary and trained rats. Aspartate transaminase levels were increased after
      training, and caffeine intake suppressed this elevation (p<0.05). Caffeine also
      diminished alanine transaminase levels in both sedentary and exercised rats
      (p<0.05). Exercise training induced a significant increase on the activity of the
      enzymes superoxide dismutase and glutathione peroxidase, as an increase on
      thiobarbituric acid-reactive substances levels was also reached (p<0.05);
      caffeine intake blunted these alterations. Caffeine intake also suppressed liver
      catalase activity in both sedentary and exercise groups (p<0.05). SIGNIFICANCE:
      Our data suggest that caffeine modified the hepatic responses associated to
      exercise-induced oxidative stress without affecting the performance, exerting
      different actions according to the tissue. However, further studies are needed to
      better understand caffeine's role on liver under exercise training.

PMID- 24334004
TI  - What a difference a day makes: quantifying the effects of birth timing
      manipulation on infant health.
AB  - Scheduling births for non-medical reasons has become an increasingly common
      practice in the United States and around the world. We exploit a natural
      experiment created by child tax benefits, which rewards births that occur just
      before the new year, to better understand the full costs of elective c-sections
      and inductions. Using data on all births in the U.S. from 1990 to 2000, we first
      confirm that expectant parents respond to the financial incentives by electing to
      give birth in December rather than January. We find that most of the manipulation
      comes from changes in the timing of c-sections. Small birth timing changes, even
      at full-term, lead to lower birthweight, a lower Apgar score, and an increase in
      the likelihood of being low birthweight. 

PMID- 24334003
TI  - Accentuation of ursolic acid on muscarinic receptor-induced ANP secretion in
      beating rabbit atria.
AB  - AIMS: Ursolic acid has recently been reported to increase both atrial natriuretic
      peptide (ANP) secretion and mechanical dynamics in rabbit atria. MAIN METHODS:
      The present study was designed to clarify the regulatory effects of ursolic acid
      on the beta-adrenergic or muscarinic receptor-mediated changes in ANP secretory
      and contractile function allowing measurement of atrial dynamics such as pulse
      pressure, stroke volume, and cAMP efflux in isolated perfused beating rabbit
      atria. KEY FINDINGS: Pretreatment with ursolic acid significantly attenuated the
      isoproterenol (beta-adrenergic agonist)-induced decrease in ANP secretion and
      increases in cAMP levels and atrial dynamics. Interestingly, ursolic acid
      concentration-dependently accentuated the acetylcholine-induced increase in ANP
      secretion and decrease in pulse pressure in the presence of isoproterenol
      (p<0.001). These findings indicate that acetylcholine-induced increase in ANP
      secretion is potentiated by ursolic acid; furthermore, acetylcholine-induced
      decrease in atrial dynamics is also potentiated by ursolic acid, suggesting that
      ursolic acid regulates muscarinic receptor-mediated secretory and contractile
      responses in perfused beating rabbit atria. SIGNIFICANCE: This implicates for the
      beneficial effects of ursolic acid in the regulation of cardiovascular and body
      fluid homeostasis.

PMID- 24334005
TI  - Measuring the effects of reducing subsidies for private insurance on public
      expenditure for health care.
AB  - This paper investigates the effects of reducing subsidies for private health
      insurance on public sector expenditure for hospital care. An econometric
      framework using simultaneous equation models is developed to analyse the
      interrelated decisions on the intensity and type of health care use and private
      insurance. The framework is applied to the context of the mixed public-private
      system in Australia. The simulation projections show that reducing premium
      subsidies is expected to generate net cost savings. This arises because the cost
      savings achieved from reducing subsidies are larger than the potential increase
      in public expenditure on hospital care. 

PMID- 24334006
TI  - MRNA expression of genes regulating lipid metabolism in ringed seals (Pusa
      hispida) from differently polluted areas.
AB  - There is a growing concern about the ability of persistent organic pollutants
      (POPs) to influence lipid metabolism. Although POPs are found at high
      concentrations in some populations of marine mammals, for example in the ringed
      seal (Pusa hispida) from the Baltic Sea, little is known about the effects of
      POPs on their lipid metabolism. An optimal regulation of lipid metabolism is
      crucial for ringed seals during the fasting/molting season. This is a
      physiologically stressful period, during which they rely on the energy stored in
      their fat reserves. The mRNA expression levels for seven genes involved in lipid
      metabolism were analyzed in liver and/or blubber tissue from molting ringed seals
      from the polluted Baltic Sea and a less polluted reference location, Svalbard
      (Norway). mRNA expression of genes encoding peroxisome proliferator-activated
      receptors (PPAR) alpha and gamma and their target genes acyl-coenzyme A oxidase 1
      (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA
      expression level of genes encoding PPARbeta, PPARgamma and their target genes
      encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were
      measured in inner and middle blubber layers. In addition, we evaluated the
      influence of molting status on hepatic mRNA expression of genes encoding PPARs
      and their target genes in ringed seals from Svalbard. Our results show higher
      mRNA expression of genes encoding hepatic PPARgamma and adipose PPARbeta, FABP4,
      and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive
      relationship between mRNA expressions of genes encoding hepatic PPARgamma,
      adipose FABP4, adipose ADIPOQ and SigmaPOP concentrations was observed. These
      findings suggest that lipid metabolism may be affected by contaminant exposure in
      the Baltic population. mRNA expression of genes encoding PPARbeta, PPARgamma,
      FABP4 and ADIPOQ were similar between the mid and inner adipose layer. Hepatic
      mRNA expression of genes encoding PPARalpha and PPARgamma was higher in the pre
      molting individuals compared to the molting ones highlighting differential
      regulation of these metabolic sensors through the molting period. 

PMID- 24334007
TI  - Assessing mechanisms of toxicant response in the amphipod Melita plumulosa
      through transcriptomic profiling.
AB  - This study describes the function of transcripts with altered abundance in the
      epibenthic amphipod, Melita plumulosa, following whole-sediment exposure to a
      series of common environmental contaminants. M. plumulosa were exposed for 48 h
      to sediments spiked and equilibrated with the following contaminants at
      concentrations predicted to cause sublethal effects to reproduction: porewater
      ammonia 30 mg L(-1); bifenthrin at 100 MUg kg(-1); fipronil at 50 MUg kg(-1);
      0.6% diesel; 0.3% crude oil; 250 mg Cu kg(-1); 400 mg Ni kg(-1); and 400 mg Zn
      kg(-1). RNA was extracted and hybridized against a custom Agilent microarray
      developed for this species. Although the microarray represented a partial
      transcriptome and not all features on the array could be annotated, unique
      transcriptomic profiles were generated for each of the contaminant exposures.
      Hierarchical clustering grouped the expression profiles together by contaminant
      class, with copper and zinc, the petroleum products and nickel, and the
      pesticides each forming a distinct cluster. Many of the transcriptional changes
      observed were consistent with patterns previously described in other crustaceans.
      The changes in the transcriptome demonstrated that contaminant exposure caused
      changes in digestive function, growth and moulting, and the cytoskeleton
      following metal exposure, whereas exposure to petroleum products caused changes
      in carbohydrate metabolism, xenobiotic metabolism and hormone cycling. Functional
      analysis of these gene expression profiles can provide a better understanding of
      modes of toxic action and permits the prediction of mixture effects within
      contaminated ecosystems.

PMID- 24334008
TI  - Synthesis, photochemistry, DNA cleavage/binding and cytotoxic properties of
      fluorescent quinoxaline and quinoline hydroperoxides.
AB  - Novel fluorescent quinoxaline and quinoline hydroperoxides were shown to perform
      dual role as both fluorophores for cell imaging and photoinduced DNA cleaving
      agents. Photophysical studies of newly synthesized quinoxaline and quinoline
      hydroperoxides showed that they all exhibited moderate to good fluorescence.
      Photolysis of quinoxaline and quinoline hydroperoxides in acetonitrile using UV
      light above 350nm resulted in the formation of corresponding ester compounds via
      gamma-hydrogen abstraction by excited carbonyl chromophore. Single strand DNA
      cleavage was achieved on irradiation of newly synthesized hydroperoxides by UV
      light (?350nm). Both hydroxyl radicals and singlet oxygen were identified as
      reactive oxygen species (ROS) responsible for the DNA cleavage. Further, we
      showed quinoline hydroperoxide binds to ct-DNA via intercalative mode. In vitro
      biological studies revealed that quinoline hydroperoxide has good
      biocompatibility, cellular uptake property and cell imaging ability. Finally, we
      showed that quinoline hydroperoxide can permeate into cells efficiently and may
      cause cytotoxicity upon irradiation by UV light. 

PMID- 24334009
TI  - Clinical and economic impact of etanercept in real-life: a prospective, non
      interventional study of etanercept in the treatment of patients with moderate to
      severe plaque psoriasis in private dermatologist settings (ESTHER).
AB  - BACKGROUND: Real-life data on the therapeutic effectiveness and costs of
      etanercept are scarce. OBJECTIVES: To assess the clinical and economic impact of
      etanercept in patients with psoriasis in Denmark and Norway. MATERIAL & METHODS:
      This prospective, non-interventional study in a private dermatologist care
      setting in Denmark and Norway included patients >=18 years with moderate to
      severe plaque psoriasis, selected for treatment with etanercept. Assessments
      during 1 year from etanercept initiation included Dermatology Life Quality Index
      (DLQI), Self-Administered Psoriasis Area and Severity Index (SAPASI) and adverse
      events. Direct and indirect costs were calculated. RESULTS: 163 subjects were
      enrolled. Baseline mean SAPASI was 19.1 . Proportion of patients with >=50%
      decrease in SAPASI from baseline was 85% and 81% at weeks 24 and 52. DLQI
      decreased significantly from 11.4 (7.0) to 3.2 (4.3) and 3.7 (4.6) at weeks 24
      and 52. Total annual costs increased from 78,000 to 286,000 DKK (p<0.0001),
      mainly due to the cost of etanercept. Outpatient-care costs and loss-of
      productivity costs decreased from 9,500 to 5,000 (p = 0.0002), and from 33,000 to
      18,000 DKK (p = 0.0105), respectively. The decrease in costs was more pronounced
      in patients who also had psoriatic arthritis. Cost increase was greatest during
      the first 6 months. CONCLUSION: Etanercept treatment was associated with
      decreased psoriasis severity and improved quality of life. Cost increase was
      driven by medication, while costs of outpatient care and loss-of-productivity
      decreased. Maintained improved quality of life was accompanied by decreasing cost
      during the second 6 month period of etanercept treatment. There were no new
      safety signals reported.

PMID- 24334010
TI  - Airflow pattern complexity during resting breathing in patients with COPD: effect
      of airway obstruction.
AB  - We investigated the influence of airway obstruction in the complexity of the
      airflow pattern in COPD and its use as a marker of disease activity. The sample
      entropy (SampEnV') and the variability (SDV') of the airflow pattern were
      measured in a group of 88 subjects with various levels of airway obstruction.
      Airway obstruction resulted in a reduction in the SampEnV' (p<0.0001) that was
      significantly correlated with spirometric indices of airway obstruction (R=0.50,
      p<0.001). The early adverse effects in mild airway obstruction were detected by
      the SampEnV' with an accuracy of 84%. SDV' increased with airway obstruction
      (p<0.002). We conclude that (1) the airflow patterns in COPD exhibit reduced
      complexity compared with healthy subjects; (2) this reduction in complexity is
      proportional to airway obstruction; and (3) the evaluation of SampEnV' may
      provide novel respiratory biomarkers suitable to facilitate the diagnosis of
      respiratory abnormalities in COPD. 

PMID- 24334011
TI  - Angina bullosa haemorrhagica.
AB  - A woman in her early 40s presented with a painless ulceration on the right side
      of the posterior palate, she had an earlier history of similar lesions after the
      rupturing of blood filled blisters in the oral cavity. On examination, a diffuse
      erythematous area and ulcers covered with necrotic slough were noticed on the
      right and left side of the posterior palate and on the right buccal mucosa. On
      follow-up visit, a large blood filled blister was noticed in the buccal
      vestibule. We advised routine haematological investigations to rule out any
      bleeding disorders and direct immunofluorescence of the affected tissue and
      perilesional areas to rule out autoimmune blistering conditions. Haematological
      investigations revealed no abnormalities and immunofluorescence testing was
      negative. A diagnosis of angina bullosa haemorrhagica was made by excluding all
      other conditions. Symptomatic treatment was given, patient was educated about the
      condition and reassured. 

PMID- 24334012
TI  - Low temperature synthesis, structural and dosimetric characterization of
      ZnAl2O4:Ce3+ nanophosphor.
AB  - Dosimetric properties of gamma-irradiated ZnAl2O4:Ce(3+) (1-9 mol%) nanophosphors
      were studied and reported for the first time. The phosphor prepared by solution
      combustion route was well characterized by powder X-ray diffraction (PXRD),
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
      techniques. PXRD patterns of calcined phosphor show pure cubic phase of
      ZnAl2O4:Ce(3+). Flake type morphology was observed from SEM studies. The particle
      size estimated by Scherrer's and Williamson Hall (W-H) plots and found to be in
      the range 11-17 nm. From photoluminescence (PL) studies two characteristic
      emission peaks at 363 and 480 nm were observed due to 5d-4f transitions of Ce(3+)
      ions. The thermoluminescence (TL) glow curves of ZnAl2O4:Ce(3+) (1-9 mol%)
      nanophosphor recorded two glow peaks 145 and 215  degrees C at a warming rate of
      2.5  degrees C s(-1). The optimized TL intensity was observed for ~5 mol% Ce(3+)
      concentration. The two TL glow peaks in the gamma-irradiated (0.1-6 kGy)
      ZnAl2O4:Ce(3+) (5 mol%) nanophosphor indicates that two set of traps were
      activated within the temperature range 145 and 215  degrees C. The kinetic
      parameters (E,b,s) associated with the prominent glow peaks were estimated using
      Chen's glow peak shape method. The intensity of the TL glow peak (145  degrees C)
      increases linearly with increase of gamma-dose upto 1 kGy above which it follows
      sub-linear behavior. Track interaction model (TIM) was used to explain the
      linearity/sub linearity/saturation behavior of TL intensity. The TL glow curves
      show simple glow peak structure, good reusability, low fading and wide range of
      linearity. Hence, the optimized ZnAl2O4:Ce(3+) (5 mol%) nanophosphor was quite
      useful for radiation dosimetry and display applications.

PMID- 24334013
TI  - Theoretical investigations on the molecular structure, vibrational spectra, HOMO
      LUMO and NBO analysis of 5-chloro-2-((4-chlorophenoxy)methyl)benzimidazole.
AB  - The optimized molecular structure, vibrational frequencies, corresponding
      vibrational assignments of 5-chloro-2-((4-chlorophenoxy)methyl)benzimidazole have
      been investigated experimentally and theoretically using Gaussian09 software
      package. The energy and oscillator strength calculated by time dependent density
      functional theory results almost compliments with experimental findings. Gauge
      including atomic orbital (1)H NMR chemical shifts calculations were carried out
      and compared with experimental data. The HOMO and LUMO analysis is used to
      determine the charge transfer within the molecule. The stability of the molecule
      arising from hyper-conjugative interaction and charge delocalization has been
      analyzed using NBO analysis. Molecular electrostatic potential was performed by
      the DFT method and the infrared intensities and Raman activities are reported.
      Mulliken's net charges have been calculated and compared with the atomic natural
      charges. Fist hyperpolarizability is calculated in order to find its role in non
      linear optics. 

PMID- 24334014
TI  - Structural, molecular orbital and optical characterizations of solvatochromic
      mixed ligand copper(II) complex of 5,5-Dimethyl cyclohexanate 1,3-dione and
      N,N,N',N'N"-pentamethyldiethylenetriamine.
AB  - In this work, a new solvatochromic mononuclear mixed ligand complex with the
      formula, Cu(DMCHD)(Me5dien)NO3 (where, DMCHD=5,5-Dimethyl cyclohexanate 1,3-dione
      and (Me5dien)=N,N,N',N'N"-pentamethyldiethylenetriamine was synthesized and
      characterized by analytical, spectral, magnetic, molar conductance, thermal
      gravimetric analysis (TGA), X-ray diffraction (XRD) and transmission electron
      microscope (TEM) measurements. The formation constant-value for copper (II)-DMCHD
      was found to be much lower than the expected for similar beta-diketones,
      revealing monobasic unidentate nature of this ligand. The d-d absorption bands of
      the prepared complex exhibit a color changes in various solvent (solvatochromic).
      Specific and non-specific interactions of solvent molecules with the complex were
      investigated using Multi Parametric Linear Regression Analysis (MLRA). Structural
      parameters of the free ligands and their Cu (II) - complex were calculated on the
      basis of semi-empirical PM3 level and compared with the experimental data. The
      crystallite size and morphology of Cu(DMCHD)(Me5dien)NO3 were examined using XRD
      analysis and TEM, revealing that the complex is well crystalline and correspond
      to the monoclinic crystal structure. The lattice strain and mean crystallite size
      were estimated by Williamson-Hall (W-H) plot using X-ray diffraction data. The
      main important absorption parameters such as extinction molar coefficient,
      oscillator strength and electric dipole strength of the principal optical
      transitions in the UV-Vis region were calculated. The analysis of absorption
      coefficient near the fundamental absorption edge reveals that the optical band
      gaps are direct allowed transitions with values of 2.78 eV and 3.59 eV. The
      present copper (II) complex was screened for its antimicrobial activity against
      Staphylococcus Aureus and Bacillus Subtilis as Gram-positive bacteria,
      Escherichia Coli and Salmonella Typhimurium as Gram-negative bacteria and Candida
      Albicans as fungus strain.

PMID- 24334015
TI  - Growth and characterization of a single crystal of Urea Adipic acid (UAA)--a
      third order nonlinear optical material.
AB  - An organic single crystal of Urea Adipic acid (UAA) was successfully grown in
      methanol solvent by slow solvent evaporation technique at room temperature (30 
      degrees C). The structure of grown crystal was elucidated from the X-ray
      diffraction study and it belongs to monoclinic system with centrosymmetric space
      group P21/c. The optical transmission spectrum of UAA has been recorded and its
      theoretical calculations were carried out to determine the linear optical
      constants such as linear absorption coefficient, extinction coefficient,
      refractive index and reflectance etc. The third-order nonlinearities of UAA
      crystal have been investigated by Z-scan method. The values of nonlinear
      refractive index (n2), the absorption coefficient (beta) and third-order
      nonlinear susceptibility (chi((3))) are found to be the order of 0.96*10(-10)
      cm(2)/W, 1.248*10(-4) cm/W and 6.44*10(-8) esu respectively. Fourier Transform
      Infra Red and Raman spectroscopy studies reveal the intermolecular interactions
      present in the UAA sample. The dielectric and mechanical measurements of the
      title compound are also reported.

PMID- 24334016
TI  - Simultaneous kinetic spectrometric determination of three flavonoid antioxidants
      in fruit with the aid of chemometrics.
AB  - A simple, inexpensive and sensitive kinetic spectrophotometric method was
      developed for the simultaneous determination of three anti-carcinogenic
      flavonoids: catechin, quercetin and naringenin, in fruit samples. A yellow
      chelate product was produced in the presence neocuproine and Cu(I) - a reduction
      product of the reaction between the flavonoids with Cu(II), and this enabled the
      quantitative measurements with UV-vis spectrophotometry. The overlapping spectra
      obtained, were resolved with chemometrics calibration models, and the best
      performing method was the fast independent component analysis (fast-ICA/PCR
      (Principal component regression)); the limits of detection were 0.075, 0.057 and
      0.063 mg L(-1) for catechin, quercetin and naringenin, respectively. The novel
      method was found to outperform significantly the common HPLC procedure.

PMID- 24334017
TI  - A surface plasmon resonance sensing method for determining captopril based on in
      situ formation of silver nanoparticles using ascorbic acid.
AB  - A new method has been proposed to sensitive detection of captopril based on
      surface plasmon resonance band of silver nanoparticles (AgNPs). The stable and
      well-dispersed AgNPs with strong plasmon resonance signal were synthesized in
      situ using a simple and rapid procedure by applying ascorbic acid as reducer and
      sodium dodecyl sulfate as stabilizer, at room temperature. It was found that, the
      decreasing of AgNPs plasmon absorbance is proportional to the concentration of
      captopril which allows the spectrophotometric sensing of this compound. The
      presented method is capable of determining captopril over a range of 0.20-2.75
      MUmol L(-1) with a limit of detection 0.07 MUmol L(-1). The relative standard
      deviation for eight replicate measurements of 1.00 and 2.50 MUmol L(-1) of
      captopril was 2.37% and 1.02%, respectively. The method was applied to the
      determination of captopril in pharmaceutical formulations with satisfactory
      results, which were in agreement with those of the official method.

PMID- 24334018
TI  - DFT computations and spectroscopic analysis of p-bromoacetanilide.
AB  - This work presents the characterization of p-bromoacetanilide (PBA) by quantum
      chemical calculations and spectral techniques. The spectroscopic properties were
      investigated by FT-IR, FT-Raman and UV-Vis techniques. The structural and
      spectroscopic data of the molecule were obtained from B3LYP/6-311++ G(d,p) and
      MPW1PW91/6-311++G(d,p) basis set calculations. The theoretical wavenumbers were
      scaled and compared with experimental FT-IR and FT-Raman spectra. The complete
      assignments were performed on the basis of the normal co-ordinate analysis (NCA),
      experimental results and potential energy distribution (PED) of the vibrational
      modes, calculated with scaled quantum mechanics (SQM) method, interpreted in
      terms of fundamental modes. The stability of molecule has been analyzed by
      NBO/NLMO analysis. The molecular orbital contributions were studied by using the
      density of states. The electronic properties like UV-Vis spectral analysis and
      HOMO-LUMO energies were reported. The calculated HOMO and LUMO energies shows
      that charge transfer interactions taking place within the molecule. Mulliken
      population analysis on atomic charges, Statistical thermodynamic properties at
      various temperatures of the PBA is also calculated. 

PMID- 24334019
TI  - Determination of the cationic amphiphilic drug-DNA binding mode and DNA-assisted
      fluorescence resonance energy transfer amplification.
AB  - Understanding the mechanism of drug-DNA binding is crucial for predicting the
      potential genotoxicity of drugs. Agarose gel electrophoresis, absorption, steady
      state fluorescence, and circular dichroism have been used in exploring the
      interaction of cationic amphiphilic drugs (CADs) such as amitriptyline
      hydrochloride (AMT), imipramine hydrochloride (IMP), and promethazine
      hydrochloride (PMT) with calf thymus or pUC19 DNA. Agarose gel electrophoresis
      assay, along with absorption and steady state fluorescence studies, reveal
      interaction between the CADs and DNA. A comparative study of the drugs with
      respect to the effect of urea, iodide induced quenching, and ethidium bromide
      (EB) exclusion assay reflects binding of CADs to the DNA primarily in an
      intercalative fashion. Circular dichroism data also support the intercalative
      mode of binding. Besides quenching, there is fluorescence exchange energy
      transfer (FRET) in between CADs and EB using DNA as a template. 

PMID- 24334020
TI  - Complex formation of Sn(II) with L-cysteine: an IR, DTA/TGA and DFT
      investigation.
AB  - The novel complex of Sn(II) with L-cysteine (L-H2Cys) has been synthesized and
      characterized by elemental analysis, TGA and IR spectroscopy. Vibrational
      assignment and DFT/PBE0/def2-TZVP ab initio simulation give evidence of cysteine
      molecule being coordinated to Sn(II) as three-dentate chelating N,O,S-donor
      ligand. The four Perdew density functionals TPSS, PBE0, PBE, TPSSh have been
      tested to provide consistency of simulated and experimental IR spectra, the best
      result is provided by unweighted Hartree-Fock density functionals (PBE, TPSS). On
      the contrary, the Hartree-Fock weighted functionals (PBE0, TPPSh) provide the
      most accurate geometry optimization. Unharmonic frequencies are obtained via ab
      initio vibrational self-consistent field (PT2-VSCF) calculations at DFT/TPSS/Def2
      TZVP level, the vibrational assignment of IR spectra has been carried out.

PMID- 24334021
TI  - Accurate calculations on 12 Lambda-S and 28 Omega states of BN+ cation: potential
      energy curves, spectroscopic parameters and spin-orbit coupling.
AB  - The potential energy curves (PECs) of 28 Omega states generated from the 12
      states (X(4)Sigma(-), 1(2)Pi, 1(2)Sigma(-), 1(2)Delta, 1(2)Sigma(+), 2(2)Pi,
      A(4)Pi, B(4)Sigma(-), 3(2)Pi, 1(6)Sigma(-), 2(2)Sigma(-) and 1(6)Pi) of the BN(+)
      cation are studied for the first time for internuclear separations from about 0.1
      to 1.0 nm using an ab initio quantum chemical method. All the Lambda-S states
      correlate to the first four dissociation channels. The 1(6)Sigma(-), 3(2)Pi and
      A(4)Pi states are found to be the inverted ones. The 1(2)Sigma(+), 2(2)Pi, 3(2)Pi
      and 2(2)Sigma(-) states are found to possess the double well. The PECs are
      calculated by the complete active space self-consistent field method, which is
      followed by the internally contracted multireference configuration interaction
      approach with the Davidson correction. Core-valence correlation correction is
      included by a cc-pCV5Z basis set. Scalar relativistic correction is calculated by
      the third-order Douglas-Kroll Hamiltonian approximation at the level of a cc-pV5Z
      basis set. The convergent behavior of present calculations is discussed with
      respect to the basis set and level of theory. The spin-orbit coupling is
      accounted for by the state interaction approach with the Breit-Pauli Hamiltonian
      using the all-electron cc-pCV5Z basis set. All the PECs are extrapolated to the
      complete basis set limit. The spectroscopic parameters are obtained, and the
      vibrational properties of 1(2)Sigma(+), 2(2)Pi, 3(2)Pi and 2(2)Sigma(-) states
      are evaluated. Analyses demonstrate that the spectroscopic parameters reported
      here can be expected to be reliably predicted ones. The conclusion is gained that
      the effect of spin-orbit coupling on the spectroscopic parameters are not obvious
      almost for all the Lambda-S states involved in the present paper.

PMID- 24334023
TI  - Keep warm and get success: the role of postischemic temperature in the mouse
      middle cerebral artery occlusion model.
AB  - Intraluminal suture middle cerebral artery occlusion (MCAO) model is the most
      frequently used model for ischemic stroke. However, the success rate of this
      model is variable among different research studies. This study aimed to
      investigate the effect of postischemic temperature on the success rate. A total
      of 100 C57BL/6 mice were randomized into two groups: control group (n=50), body
      temperature was allowed to self-regulate after MCAO; temperature-controlled group
      (n=50), mice were kept warm in an incubator for 12 h after MCAO. The body
      temperature of animals was measured before, during, and for 12 h after MCAO.
      Neurological deficits and infarct volumes were measured at 24 h after MCAO. There
      was significant difference (P<0.05) of the body temperature between the two
      groups from 0.5 h to 3.5 h post ischemia. Moreover, there was obvious difference
      between the success rates of the two groups (control group: 52%, temperature
      controlled group: 84%, P<0.05). In the successful models, infarct volume was
      significantly (P<0.05) higher in temperature-controlled group (53.44%+/-9.83%,
      n=42) than control group (45.63%+/-10.24%, n=26). There was significant
      difference of the modified neurological severity scores (P<0.05), left adhesive
      tests (P<0.05) between the two groups. Our data demonstrated that postischemic
      warming contributed to the success of mouse MCAO model.

PMID- 24334024
TI  - Periodic maternal deprivation may modulate offspring anxiety-like behavior
      through mechanisms involving neuroplasticity in the amygdala.
AB  - Maternal care has been shown to affect the development of behavioral and
      endocrine systems. In rats, periodic maternal deprivation (PMD) serves as an
      early life stressor that directly influences maternal care by promoting more pup
      directed behaviors in stressed dams. To further assess the qualities of PMD that
      may ameliorate long-term anxiety effects in trait anxiety animals, we coded
      behaviors across lactation (postnatal day (PND) 5, 16, 21) in dams phenotyped as
      high (HAn) and low-anxiety (LAn). We assessed anxiety-like behavior in male
      offspring using the elevated plus maze (EPM), focusing on percent open arm (%OA)
      time and latency to enter OA (OA LAT) as measures of anxiety-like behavior.
      Finally, we examined the brains of representative male pups to determine if the
      stress-related protein brain-derived neurotrophic factor (BDNF) might show
      persistent changes in the amygdala. Dams phenotyped as HAn had lower %OA time and
      longer OA LAT relative to dams designated as LAn. During PMD, HAn dams had higher
      incidences of licking-grooming (L/G) and more pup-directed behaviors on PND 5 and
      16 compared to LAn dams. Further, as adults, HAn male offspring exhibited less
      anxiety traits than their maternal line with greater %OA time and %OA entries
      relative to LAn. HAn offspring showed markedly more BDNF immunoreacted cells in
      the amygdala than LAn. The combination of these findings suggests that the mild
      stressor, PMD alters anxiety-like behavior in offspring likely by influencing HAn
      dams' L/G activity and altering stress related proteins in the amygdala. 

PMID- 24334022
TI  - Abnormal kalirin signaling in neuropsychiatric disorders.
AB  - Changes in dendritic spines structure and function play a critical role in a
      number of physiological processes, including synaptic transmission and
      plasticity, and are intimately linked to cognitive function. Alterations in
      dendritic spine morphogenesis occur in a number of neuropsychiatric disorders and
      likely underlie the cognitive and behavioral changes associated with these
      disorders. The neuronal guanine nucleotide exchange factor (GEF) kalirin is
      emerging as a key regulator of structural and functional plasticity at dendritic
      spines. Moreover, a series of recent studies have genetically and functionally
      linked kalirin signaling to several disorders, including schizophrenia and
      Alzheimer's disease. Kalirin signaling may thus represent a disease mechanism and
      provide a novel therapeutic target.

PMID- 24334025
TI  - Seroprevalence of measles IgG among HIV-1-infected and uninfected Kenyan adults.
AB  - Despite global efforts to reduce measles incidence, outbreaks continue to occur
      in developing countries where HIV-1-infected adults represent a vulnerable
      population. Immunization campaigns have targeted children, although little is
      known about the levels of measles protection in adult populations in Kenya. The
      objective of this study was to determine seroprevalence and titers of measles IgG
      among HIV-1-infected and uninfected adults in Nairobi, Kenya. The presence of
      anti-measles IgG was measured in cryopreserved serum of 257 HIV-1-infected and
      367 uninfected adults using a commercial ELISA (Enzygnost, Germany). The measles
      IgG concentration was calculated for those samples that were positive. Overall,
      96% of adults were measles seropositive and the mean measles IgG concentration
      among those who were seropositive was 4134 mIU/ml, which is well above previously
      reported protective levels. There was no statistical difference in seroprevalence
      or antibody concentration between the HIV-infected and HIV-uninfected groups.
      While local vaccination efforts and circulating measles infection likely
      contribute to this high measles seroprevalence rate, these data are unique to an
      urban population and may not reflect a country-wide distribution. Our results
      suggest that reduced immunity among HIV-1-infected adults is not a major
      contributor to measles resurgence in Kenya. 

PMID- 24334026
TI  - Evolution of dengue in Sri Lanka-changes in the virus, vector, and climate.
AB  - Despite the presence of dengue in Sri Lanka since the early 1960s, dengue has
      become a major public health issue, with a high morbidity and mortality. Aedes
      aegypti and Aedes albopictus are the vectors responsible for the transmission of
      dengue viruses (DENV). The four DENV serotypes (1, 2, 3, and 4) have been co
      circulating in Sri Lanka for more than 30 years. The new genotype of DENV-1 has
      replaced an old genotype, and new clades of DENV-3 genotype III have replaced
      older clades. The emergence of new clades of DENV-3 in the recent past coincided
      with an abrupt increase in the number of dengue fever (DF)/dengue hemorrhagic
      fever (DHF) cases, implicating this serotype in severe epidemics. Climatic
      factors play a pivotal role in the epidemiological pattern of DF/DHF in terms of
      the number of cases, severity of illness, shifts in affected age groups, and the
      expansion of spread from urban to rural areas. There is a regular incidence of
      DF/DHF throughout the year, with the highest incidence during the rainy months.
      To reduce the morbidity and mortality associated with DF/DHF, it is important to
      implement effective vector control programs in the country. The economic impact
      of DF/DHF results from the expenditure on DF/DHF critical care units in several
      hospitals and the cost of case management. 

PMID- 24334027
TI  - Evidence for the involvement of type I interferon in pulmonary arterial
      hypertension.
AB  - RATIONALE: Evidence is increasing of a link between interferon (IFN) and
      pulmonary arterial hypertension (PAH). Conditions with chronically elevated
      endogenous IFNs such as systemic sclerosis are strongly associated with PAH.
      Furthermore, therapeutic use of type I IFN is associated with PAH. This was
      recognized at the 2013 World Symposium on Pulmonary Hypertension where the urgent
      need for research into this was highlighted. OBJECTIVE: To explore the role of
      type I IFN in PAH. METHODS AND RESULTS: Cells were cultured using standard
      approaches. Cytokines were measured by ELISA. Gene and protein expression were
      measured using reverse transcriptase polymerase chain reaction, Western blotting,
      and immunohistochemistry. The role of type I IFN in PAH in vivo was determined
      using type I IFN receptor knockout (IFNAR1(-/-)) mice. Human lung cells responded
      to types I and II but not III IFN correlating with relevant receptor expression.
      Type I, II, and III IFN levels were elevated in serum of patients with systemic
      sclerosis associated PAH. Serum interferon gamma inducible protein 10 (IP10;
      CXCL10) and endothelin 1 were raised and strongly correlated together. IP10
      correlated positively with pulmonary hemodynamics and serum brain natriuretic
      peptide and negatively with 6-minute walk test and cardiac index. Endothelial
      cells grown out of the blood of PAH patients were more sensitive to the effects
      of type I IFN than cells from healthy donors. PAH lung demonstrated increased
      IFNAR1 protein levels. IFNAR1(-/-) mice were protected from the effects of
      hypoxia on the right heart, vascular remodeling, and raised serum endothelin 1
      levels. CONCLUSIONS: These data indicate that type I IFN, via an action of
      IFNAR1, mediates PAH.

PMID- 24334029
TI  - Crystal structure of a novel asymmetrically engineered Fc variant with improved
      affinity for FcgammaRs.
AB  - Enhancing the effector function by optimizing the interaction between Fc and
      Fcgamma receptor (FcgammaR) is a promising approach to enhance the potency of
      anticancer monoclonal antibodies (mAbs). To date, a variety of Fc engineering
      approaches to modulate the interaction have been reported, such as afucosylation
      in the heavy chain Fc region or symmetrically introducing amino acid
      substitutions into the region, and there is still room to improve FcgammaR
      binding and thermal stability of the CH2 domain with these approaches. Recently,
      we have reported that asymmetric Fc engineering, which introduces different
      substitutions into each Fc region of heavy chain, can further improve the
      FcgammaR binding while maintaining the thermal stability of the CH2 domain by
      fine-tuning the asymmetric interface between the Fc domain and FcgammaR. However,
      the structural mechanism by which the asymmetrically engineered Fc improved
      FcgammaR binding remained unclear. In order to elucidate the mechanism, we solved
      the crystal structure of a novel asymmetrically engineered Fc, asym-mAb23, in
      complex with FcgammaRIIIa. Asym-mAb23 has enhanced binding affinity for both
      FcgammaRIIIa and FcgammaRIIa at the highest level of previously reported Fc
      variants. The structural analysis reveals the features of the asymmetrically
      engineered Fc in comparison with symmetric Fc and how each asymmetrically
      introduced substitution contributes to the improved interaction between asym
      mAb23 and FcgammaRIIIa. This crystal structure could be utilized to enable us to
      design a more potent asymmetric Fc. 

PMID- 24334028
TI  - beta-arrestin1-biased beta1-adrenergic receptor signaling regulates microRNA
      processing.
AB  - RATIONALE: MicroRNAs (miRs) are small, noncoding RNAs that function to post
      transcriptionally regulate gene expression. First transcribed as long primary miR
      transcripts (pri-miRs), they are enzymatically processed in the nucleus by Drosha
      into hairpin intermediate miRs (pre-miRs) and further processed in the cytoplasm
      by Dicer into mature miRs where they regulate cellular processes after activation
      by a variety of signals such as those stimulated by beta-adrenergic receptors
      (betaARs). Initially discovered to desensitize betaAR signaling, beta-arrestins
      are now appreciated to transduce multiple effector pathways independent of G
      protein-mediated second messenger accumulation, a concept known as biased
      signaling. We previously showed that the beta-arrestin-biased betaAR agonist,
      carvedilol, activates cellular pathways in the heart. OBJECTIVE: Here, we tested
      whether carvedilol could activate beta-arrestin-mediated miR maturation, thereby
      providing a novel potential mechanism for its cardioprotective effects. METHODS
      AND RESULTS: In human cells and mouse hearts, carvedilol upregulates a subset of
      mature and pre-miRs, but not their pri-miRs, in beta1AR-, G-protein-coupled
      receptor kinase 5/6-, and beta-arrestin1-dependent manner. Mechanistically, beta
      arrestin1 regulates miR processing by forming a nuclear complex with hnRNPA1 and
      Drosha on pri-miRs. CONCLUSIONS: Our findings indicate a novel function for
      beta1AR-mediated beta-arrestin1 signaling activated by carvedilol in miR
      biogenesis, which may be linked, in part, to its mechanism for cell survival.

PMID- 24334030
TI  - SmartShapeTM technology. Modifying the shape of the beef cuberoll and the
      consumer response to shaped scotch fillet steaks.
AB  - SmartShapeTM is a novel meat processing technology that uses air pressure to
      compress and elongate whole cold-boned primals and packages them to retain form.
      A two stage study was conducted. The first stage established the ability of the
      SmartShapeTM treated beef cube roll (m. longissimus lumborum) to retain shape in
      a commercial setting. Twelve hours chilling time following treatment was found to
      be adequate for steaks to retain their shape for up to 24h after slicing. Steak
      shape and size did not change substantially until after cooking, when the steaks
      looked less formed. In the second stage a survey was conducted of 421 consumers
      to clarify the response to the shaping of a subset of raw and cooked scotch
      fillet steaks. There was no difference in preference for shaped or control
      steaks. A secondary survey found that informed consumers were more amenable to
      the SmartShapeTM scotch fillet steaks presented here, but would not pay a premium
      for them. 

PMID- 24334031
TI  - Influence of sodium chloride and pH during acidic marination on water retention
      and mechanical properties of turkey breast meat.
AB  - Turkey breast cubes underwent acidic marination in the presence of salt. The
      transfer of water, salt and acid was measured, and texture was assessed on the
      cooked meat. While significant mass gains were observed during marination, from
      20 minutes of immersion onwards, only long durations produced an overall matter
      balance greater than that of non-marinated meat. From the first minutes of
      immersion, these transfers caused hardening, regardless of the presence of salt
      in the marinade. For longer durations, only in the absence of salt was
      significant tenderizing seen in comparison to the non-marinated control. This
      effect appears to be due on the one hand to passing the isoelectric pH of the
      meat during acidification, and on the other hand to setting up antagonistic
      mechanisms breaking down or reinforcing connective tissues by acid and salt
      respectively. The high degree of tenderization observed in a water-acid solution
      can be explained partly by dilution of the fiber load per section unit due to
      protein solubilization.

PMID- 24334032
TI  - Maternal dietary fat affects the LT muscle fatty acid composition of progeny at
      weaning and finishing stages in pigs.
AB  - The present study was conducted to investigate whether maternal dietary fat
      affects the fatty acid composition of the longissimus thoracis (LT) muscle in
      offspring pigs at weaning and finishing stages. Fourteen sows were randomly
      assigned to a control or a high fat (HF) group. The HF sows received a diet
      containing 8% corn oil starting seven days before farrowing until weaning. The
      results showed that a high-fat diet significantly increased the contents of serum
      lipid-related indexes in the sows. Although the triglyceride content did not
      change, the C18:2n-6 content was higher in the colostrum and in the LT muscle of
      offspring pigs at both investigated stages. The total n-6 content and the n-6/n-3
      ratio generally increased. This study demonstrated that maternal dietary fat
      during lactation affects the fatty acid composition of the LT muscle of progeny
      at weaning, and can have persistent effects in later life. 

PMID- 24334034
TI  - Habituation to organic acid anions induces resistance to acid and bile in
      Listeria monocytogenes.
AB  - We evaluated the intrinsic and inducible resistance of four human pathogenic
      strains of Listeria monocytogenes to acid and bile, factors associated with
      virulence. Cells were grown in media at pH 7.4, or in media at pH 6.0 containing
      0 (HCl control) or 4.75 mM of different organic acids, harvested at stationary or
      mid log phase, and challenged for 1h in acid or bile. Stationary phase cells were
      intrinsically more resistant to either challenge than log phase cells, and large
      differences between strains were evident among the latter. Compared to the HCl
      control, habituation to log phase with organic acids induced significant (p<0.05)
      and meaningful (>=1 log) increases in acid resistance of three of four strains
      tested, and in bile resistance of two strains suggesting that exposure to organic
      acid anions may enhance virulence in L. monocytogenes.

PMID- 24334033
TI  - Dietary lecithin improves dressing percentage and decreases chewiness in the
      longissimus muscle in finisher gilts.
AB  - The influence of dietary lecithin at doses of 0, 4, 20 or 80 g/kg fed to finisher
      gilts for six weeks prior to slaughter on growth performance, carcass quality and
      pork quality was investigated. M. longissimus lumborum (loin) was removed from 36
      pig carcasses at 24h post-mortem for Warner-Bratzler shear force, compression,
      collagen content and colour analyses. Dietary lecithin increased dressing
      percentage (P=0.009). Pork chewiness and collagen content were decreased by
      dietary lecithin (P<0.05, respectively), suggesting that improved chewiness may
      be due to decreased collagen content. However, dietary lecithin had no effect on
      shear force, cohesiveness or hardness (P>0.05, respectively). Dietary lecithin
      reduced loin muscle L* values and increased a* values (P<0.05, respectively) but
      no changes on b* values (P=0.56). The data showed that dietary lecithin improved
      dressing percentage and resulted in less chewy and less pale pork.

PMID- 24334035
TI  - Fatty acid profile, carcass and meat quality traits of young Nellore bulls fed
      crude glycerin replacing energy sources in the concentrate.
AB  - Carcass and meat quality traits of 60 Nellore young bulls fed diets without crude
      glycerin (CG); with CG replacing corn (CGc; 10% of dry matter - DM) in the
      concentrate; and with CG replacing soybean hull (CGsh; 10% of DM) in the
      concentrate were evaluated. Diets were evaluated at two concentrate levels (CLs).
      The CL did not affect cold carcass weight (CCW; P=0.6074), cold carcass dressing
      (CCD; P=0.9636), rib fat thickness (RFT; P=0.8696) and longissimus muscle area
      (LMA; P=0.7524). Animals fed diets with CGc or CGsh showed meat with greater
      deposition of monounsaturated fatty acid (MUFA; P=0.0022) and CLA (18:2 cis-9,
      trans-11) contents (P=0.0001) than animals fed diets without CG. The inclusion of
      10% of CG in diets CGc or CGsh does not affect the carcass and meat quality
      traits; however, it increases the MUFA and CLA contents in beef, although these
      changes are very small in nutritional terms. 

PMID- 24334036
TI  - The impact of salt replacers and flavor enhancer on the processing
      characteristics and consumer acceptance of restructured cooked hams.
AB  - Two salt replacers (Ocean's Flavor - OF45, OF60) and one flavor enhancer
      [FonterraTM 'Savoury Powder' (SP)] were evaluated for their ability to
      effectively reduce sodium, while maintaining the functional and sensory
      properties of restructured hams. Product functionality and safety were assessed
      using instrumental measures (yield, purge, pH, expressible moisture, proximate
      composition, sodium content, color, texture) and microbiological assessment.
      Sensory attributes were evaluated using consumer sensory panelists. All
      alternative formulations resulted in products with sodium contents below the
      Health Check(TM) Program guidelines, without detrimental effect on water binding
      and texture in treatments when NaCl was substituted with sea salt replacers
      (OF45, OF60). Sodium reduction had no effect on the shelf life of the cooked ham
      with up to 60 days of refrigerated storage. Consumer hedonics for flavor and
      aftertaste were lower for OF45 and OF60 compared to control, suggesting that
      these salt replacers may not be appropriate for inclusion in these products.

PMID- 24334037
TI  - Effect of an active packaging with citrus extract on lipid oxidation and sensory
      quality of cooked turkey meat.
AB  - An antioxidant active packaging was prepared by coating a citrus extract,
      consisting of a mixture of carboxylic acids and flavanones, on polyethylene
      terephthalate trays. The effect of the packaging in reducing lipid oxidation in
      cooked turkey meat and on meat pH, colour characteristics and sensorial
      parameters was investigated. An untrained sensory panel evaluated the odour,
      taste, tenderness, juiciness and overall acceptability of the meat, using
      triangle, paired preference and quantitative response scale tests. A comparison
      between the antioxidant effects of the different components of the extract was
      also carried out. The packaging led to a significant reduction in lipid
      oxidation. After 2 days of refrigerated storage the sensory panel detected
      differences in odour and, after 4 days, rated the meat stored in the active
      packaging higher for tenderness and overall acceptability. Citric acid appeared
      to be the most important component of the extract with regard to its antioxidant
      potency.

PMID- 24334038
TI  - Influence of selected quality factors of beef on the profile and the quantity of
      heterocyclic aromatic amines during processing at high temperature.
AB  - New factors were identified impacting significantly on the formation of HAA
      during grilling. The number and profile of HAA in grilled beef depend on the
      fattening system (intensive and semi-intensive), and the effect of the animal's
      sex. The fewest HAAs were formed in rib steak from heifers from a semi-intensive
      fattening system. A significant effect of storage of meat in refrigerated
      conditions (5 to 15 days) was also demonstrated on the formation of HAA during
      grilling. The longer the raw meat was stored, the more HAA was formed during
      grilling. The quantity of HAA was strongly correlated with the content of free
      amino acids and a very strong correlation was found with an increasing content of
      free purine and pyrimidine bases and their nucleosides.

PMID- 24334039
TI  - Healthy reduced-fat Bologna sausages enriched in ALA and DHA and stabilized with
      Melissa officinalis extract.
AB  - Reduced-energy and reduced-fat Bologna products enriched with omega-3
      polyunsaturated fatty acids were formulated by replacing the pork back-fat by an
      oil-in-water emulsion containing a mixture of linseed-algae oil stabilized with a
      lyophilized Melissa officinalis extract. Healthier composition and lipid profile
      was obtained: 85 kcal/100 g, 3.6% fat, 0.6 g ALA and 0.44 g DHA per 100 g of
      product and omega-6/omega-3 ratio of 0.4. Technological and sensory problems were
      not detected in the new formulations. Reformulation did not cause oxidation
      problems during 32 days of storage under refrigeration. The results suggest that
      it is possible to obtain reduced-fat Bologna-type sausages rich in ALA and DHA
      and stabilized with natural antioxidants, applying the appropriate technology
      without significant effects on the sensory quality, yielding interesting products
      from a nutritional point of view.

PMID- 24334040
TI  - Effect of enzymatic hydrolysis with subsequent mild thermal oxidation of tallow
      on precursor formation and sensory profiles of beef flavours assessed by partial
      least squares regression.
AB  - Effects of different pretreatments of tallow on flavour precursor development and
      flavour profiles of beef flavours (BFs) were evaluated. Analysis of free fatty
      acids and volatiles of tallow by GC and GC-MS indicated that the enzymatic
      hydrolyzed-thermally oxidized tallow formed the most characteristic flavour
      precursors compared with others. The results of descriptive sensory analysis
      confirmed that beef flavour 4 from enzymatic hydrolyzed-thermally oxidized tallow
      had the strongest beefy, meaty and odour characteristics, followed by beef
      flavour 2 from oxidized tallow. Electronic nose data confirmed the accuracy of
      the sensory analysis results. The correlation analysis of 51 volatile compounds
      in tallow and sensory attributes of BFs showed that some compounds, especially
      aldehydes, made a significant contribution to sensory attributes. Correlation
      analysis of free fatty acids and sensory attributes through partial least squares
      regression (PLSR) confirmed that the moderate enzymatic hydrolysis-thermal
      oxidation pretreatment of tallow was necessary to achieve the characteristic beef
      flavour. 

PMID- 24334041
TI  - The efficacy of pulsed ultrahigh current for the stunning of cattle prior to
      slaughter.
AB  - We present results from the development of a new system of reversible electrical
      stunning of cattle. A single-pulse ultra-high current (SPUC) was generated from a
      capacitance discharge current spike of at least 5000 V at 70 A, for approximately
      50 ms. Ninety-seven cattle were stunned in three experimental protocols. With
      improvements made to the design of the stun box and charge delivered, 38 cattle
      were either stunned and immediately jugulated or monitored for signs of
      reappearance of brain stem reflexes at which point a concussion stun was
      administered. This use of the SPUC charge, provided as a biphasic-pulse waveform,
      resulted in a high level of stunning efficacy, with unconsciousness lasting for
      up to 4 min. These results were supported by EEG data taken from a subsequent
      cohort of stunned cattle. The SPUC stun also apparently eliminated post-stun
      grand mal seizures that can occur following short-acting conventional electrical
      stun, with its associated negative consequences on operator safety and meat
      quality.

PMID- 24334042
TI  - Quality and shelf life evaluation of pork nuggets incorporated with fermented
      bamboo shoot (Bambusa polymorpha) mince.
AB  - Pork nuggets were processed by incorporating fermented bamboo shoot mince and
      their physico-chemical, microbiological and sensory characteristics were
      evaluated during 35 day storage at refrigeration temperature (4+/-1  degrees C).
      Addition of fermented bamboo shoot significantly affects the pH, moisture,
      protein, fat, fiber, instrumental color values and texture profiles of nuggets,
      especially at 6% and 8% addition levels. Nuggets with 6% and 8% FBSM had
      significantly lower TBARS values at the end of the storage period (i.e. 0.39 and
      0.33 mg malonaldehyde/kg respectively) compared to the control (0.84 mg
      malonaldehyde/kg). Bamboo shoot addition significantly improved the microbial and
      sensory qualities of the pork nuggets. Incorporation of fermented bamboo shoot at
      8% level increased the shelf life of pork nuggets by at least two weeks i.e. from
      21 days to 35 days at 4+/-1  degrees C compared to the control.

PMID- 24334043
TI  - Use of smart photochromic indicator for dynamic monitoring of the shelf life of
      chilled chicken based products.
AB  - This study evaluated the applicability of a photochromic time temperature
      indicator (TTI) to monitor the time-temperature history and shelf life of chilled
      boneless chicken breast. The results showed that the smart indicator showed good
      reproducibility during the discoloring process in all the conditions
      investigated. The response was not only visibly interpretable but also well
      adaptable to measurement using appropriate equipment. For an activation
      configuration of 4 s of ultraviolet light (UV) per label, the TTI's rate of
      discoloration was similar to the quality loss of the meat samples analyzed. Thus,
      the photochromic label (4 s UV/label) attached to the samples set out to be a
      dynamic shelf-life label, assuring consumers the final point of quality of
      chilled boneless chicken breast in an easy and precise form, providing a reliable
      tool to monitor the supply chain of this product.

PMID- 24334044
TI  - Effects of blade tenderization, aging method and aging time on meat quality
      characteristics of Longissimus lumborum steaks from cull Holstein cows.
AB  - The effects of blade tenderization (BT), two aging methods (dry (D) and wet (W)),
      and aging time (2 and 23 d) on tenderness, color, and sensory properties of
      Longissimus lumborum muscles from 12 cull Holstein cows were evaluated. Dry-aged
      loins had higher combined trim and aging losses than control (C) for both D- and
      W-aging, mostly because of excess trim losses. BT steaks had WBSF of 33.13 N
      while C steaks had WBSF of 41.46 N (P=0.09). Aging decreased WBSF. Blade
      tenderized steaks had higher cook loss than C steaks. Aging, W-aging, and BT*W
      aging improved myofibrillar (sensory) tenderness scores. Aging and/or BT improves
      sensory panel tenderness cull cow Longissimus lumborum steaks. Aging and blade
      tenderization combined can increase tenderness and value of Longissimus steaks
      from cull Holstein cows.

PMID- 24334045
TI  - Chemical composition and structural characteristics of Arabian camel (Camelus
      dromedarius) m. longissimus thoracis.
AB  - Saudi Arabian camels of four breeds (6 animals per breed) were used to evaluate
      characteristics and quality of their meat. Chemical composition, fibre cross
      sectional area, collagen content, muscle metabolism, cooking loss, pH at 24 h
      post mortem, colour values (except redness) and shear force of Longissimus
      thoracis (LT) muscle did not differ between the breeds. Elevated pH values and
      short sarcomeres reduced overall tenderisation, with a difference between
      myofibril fragmentation index (P<0.001) and sarcomere length (P<0.05) between
      breeds. A positive correlation was observed between the activities of the
      mitochondrial enzymes (r>0.49), between the glycolytic activities (PFK and LDH)
      (r=0.61) and between Myosin Heavy Chain IIa and LDH activity. The intramuscular
      fat content was positively associated with redness and muscle oxidative
      metabolism, whereas shear force had a slight positive association with collagen
      content and muscle glycolytic metabolism and a negative association with muscle
      oxidative metabolism and muscle fibre area.

PMID- 24334046
TI  - Effect of fat quality on sausage processing, texture, and sensory
      characteristics.
AB  - Fresh pork sausage was manufactured to determine the effects of animal diet
      (unsaturated or control) and inclusion of corn oil during processing (0% and 14%
      fat replacement). Bologna was manufactured to investigate only diet effects.
      Processing, textural, sensory, visual, and storage characteristics were
      evaluated. Processing yield was improved 2.9 percentage units in fresh sausage
      but reduced 1.8 units in bologna in unsaturated compared with control diets.
      Break strength of fresh sausage was reduced 0.6 kg by oil inclusion. Both
      unsaturated fat and including oil during processing resulted in softer texture of
      fresh sausage, while increased unsaturation in bologna resulted in firmer or
      unchanged textural properties. Fresh sausage with oil was lighter colored (5.3 L*
      units increased) with more fat smearing. In fresh sausage, lipid oxidation
      remained below 1mg/kg MDA during 12 weeks frozen storage. Overall, changes in fat
      quality minimally affected sausage quality, likely providing acceptable products
      to consumers.

PMID- 24334047
TI  - Temperature of frozen storage affects the nature and consequences of protein
      oxidation in beef patties.
AB  - The effect of three frozen storage temperatures (-8, -18 and -80  degrees C) on
      protein oxidation in beef patties was studied through the analysis of novel
      oxidation markers. Additionally, the connection between lipid and protein
      oxidation and the impact of the latter on particular quality traits (water
      holding capacity, color and texture) of subsequently processed beef patties
      (cooking/cold-stored) were investigated. Protein oxidation was measured as the
      loss of tryptophan fluorescence and formation of diverse lysine oxidation
      products (alpha-aminoadipic semialdehyde, alpha-aminoadipic acid and Schiff
      bases). Lipid oxidation was assessed by levels of thiobarbituric acid reactive
      substances and hexanal. A significant effect of storage temperature on protein
      oxidation was detected. Frozen storage increased the susceptibility of meat
      proteins to undergo further oxidation during processing. Timely interactions were
      found between lipid and protein oxidation. Plausible mechanisms by which
      oxidative damage to proteins may have an impact in particular quality traits are
      thoroughly discussed.

PMID- 24334048
TI  - Effect of including linseed in a concentrate fed to young bulls on intramuscular
      fatty acids and beef color.
AB  - The effect of varying concentrate composition to include 5% linseed and 200 IU of
      vitamin E on the growth performance, fatty acid composition, and muscle color
      during shelf life was assessed in 46 young Pirenaica bulls finished to two
      fatness levels. Adding 5% linseed lowered the dressing rate without altering
      daily gain or carcass classification. It likewise did not alter the total
      saturated, monounsaturated, or polyunsaturated fatty acids in the intramuscular
      fat, though the percentage of alpha-linolenic acid and n-3 fatty acids increased
      significantly while the n-6 fatty acid to n-3 fatty acid ratio decreased. Higher
      subcutaneous fat cover depth at slaughter increased the total percentage of oleic
      acid and monounsaturated fatty acids without affecting the percentage of
      saturated or polyunsaturated fatty acids. Adding 200 IU of vitamin E in addition
      to linseed did not alter the color of film-wrapped fresh meat during storage in
      darkness.

PMID- 24334049
TI  - The application of high-pressure treatment in the reduction of salt levels in
      reduced-phosphate breakfast sausages.
AB  - This study investigated the effects of high pressure (HP) treatment of pork meat
      before manufacturing sausages with reduced salt levels and compared them to
      sausages manufactured with untreated meat (control sausages). A 2*5 factorial
      design was set up incorporating two pressure levels (0 or 150 MPa) and five salt
      levels (0.5, 1.0, 1.5, 2.0 and 2.5%). Most quality attributes were affected when
      salt levels were reduced below 1.5%. Fat loss (FL) was (P<0.05) affected by salt
      level; samples with <1.5% salt had the highest FL. HP treatment increased
      emulsion stability and reduced cook loss (CL) compared to control sausages.
      Increased CL was observed when salt was reduced below 2.0%. Salt reduction below
      1.5% adversely affected colour, sensory and texture attributes. Independent of
      salt, HP treatment affected adversely juiciness and cohesiveness while
      adhesiveness was improved. Overall, there is potential to manufacture sausages
      maintaining organoleptic and functional properties traditionally associated with
      sausages using HP treated meat.

PMID- 24334050
TI  - Effect of Ganoderma lucidum (Reishi mushroom) or Olea europaea (olive) leaves on
      oxidative stability of rabbit meat fortified with n-3 fatty acids.
AB  - The objective of the present study was to evaluate the effect of Ganoderma
      lucidum (Reishi mushroom) or Olea europaea (olive tree) leaves on oxidative
      stability of rabbit meat fortified with n-3 fatty acids. Forty-eight slovenska
      kunka (SIKA) rabbits were divided into four homogeneous groups. The control group
      (CONT-) received diet with 6% palm fat; other groups received diet with 6%
      linseed oil and were either unsupplemented (CONT+) or supplemented with 1% of G.
      lucidum (REISHI) or O. europaea leaves (OLIVE). Rabbits were slaughtered and
      fatty acid composition, concentration of vitamin E and malondialdehyde (MDA) in
      back muscle were analyzed. The results showed that linseed oil addition improved
      fatty acid composition by increasing polyunsaturated fatty acid (PUFA)
      proportion, decreasing proportion of saturated fatty acid (SFA) and reducing n
      6/n-3 ratio in rabbit meat. Groups that were supplemented with linseed oil had
      lower content of alpha-tocopherol and higher content of gamma-tocopherol,
      compared to the CONT- group. The addition of potential antioxidants did not
      effectively prevent oxidation of rabbit meat. 

PMID- 24334051
TI  - Effect of vitamin E supplementation on fatty acid composition of muscle and
      adipose tissues of indoor lambs with special attention on rumen-derived trans
      monounsaturated fatty acids.
AB  - Thirty male lambs were assigned to one of 3 concentrate diets supplemented with
      45 (E0), 286 (E1) or 551 (E2) mg/kg DM of dl-alpha-tocopheryl acetate to test the
      effect of vitamin E supplementation on muscle, caudal and perirenal fatty acid
      (FA) compositions. Specific attention was paid to C18:1 10t, usually observed in
      high proportions with high-starch or high-unsaturated FA diets. Vitamin E
      supplementation increased the alpha-tocopherol plasma concentrations of lambs. It
      did not modify lamb growth and slaughter parameters. Vitamin E supplementation
      did not modify FA composition in most tissues but it increased the C18:2 n
      6/C18:3 n-3 ratio in muscle and adipose tissues of the E1 group compared to E0
      and E2 groups. Vitamin E supplementation enhanced the C18:1 10t proportion in
      muscle and adipose tissues and it decreased the C18:2 9c,11t proportion in
      adipose tissues, especially in the E2 group. These changes may not be favourable
      for the nutritional value of lamb meat.

PMID- 24334052
TI  - Lipid and protein stability and sensory evaluation of ostrich (Struthio camelus)
      droewors with the addition of rooibos tea extract (Aspalathus linearis) as a
      natural antioxidant.
AB  - The effect of rooibos tea extract (RBTE 0%, 0.25%, 0.50%, 1.00%) as a natural
      antioxidant on the lipid and protein stability of ostrich droewors (traditional
      South African dried sausage) after a 15 day drying period was investigated. The
      lipid stability of the droewors increased with 0.25% RBTE having lower TBARS. The
      protein stability of the droewors did not differ (P>=0.05) between treatments.
      The heme-iron content did not differ (P>=0.05) between the treatments and
      increased from day 0 to day 15. Drying resulted in a decrease in the total
      moisture content by 45% and a corresponding increase in all other components.
      There were no differences between the moisture, fat and ash contents between
      treatments within a specific day. The droewors had high concentrations of oleic
      acid, palmitic acid and linoleic acid. The addition of RBTE also improved the
      sensory attributes and can thus be added and marketed as a natural flavourant
      from 'out of Africa' for a traditional South African meat product.

PMID- 24334053
TI  - Effects of different sources of fat (calcium soap of palm oil vs. extruded
      linseed) in lactating ewes' diet on the fatty acid profile of their suckling
      lambs.
AB  - The main objective of this study was to evaluate the effects of supplementing
      lactating ewe diets with extruded linseed on the fatty acid (FA) composition of
      intramuscular and subcutaneous fat depots of suckling lambs. Twenty-four pregnant
      Churra ewes were divided into two groups based on the milk production, age, body
      weight and parity, and assigned to one of two treatments. Each ewe of the Control
      treatment was supplemented with 70 g/day of FAs from a calcium soap of palm oil,
      while the other treatment group (Lin) was supplemented with 128 g/day of extruded
      linseed. All lambs were reared exclusively on milk and were slaughtered when they
      reached 11 kg live weight. FA profiles of ewe milk, lamb meat and subcutaneous
      adipose tissue were determined by GC. Lamb performance was not affected by the
      treatments. Muscle fat and adipose tissue from the Lin treatment showed higher
      proportions of polyunsaturated fatty acids (PUFA). The percentages of alpha
      linolenic (C18:3 n-3), docosahexaenoic (C22:6 n-3), vaccenic (trans-11 C18:1) and
      rumenic (cis-9, trans-11 C18:2) acids in both fat depots were higher in Lin than
      in Control suckling lambs. Furthermore, meat fat from Lin carcasses displayed a
      lower n-6/n-3 ratio than Control samples. Intramuscular depots clearly showed a
      greater content of PUFA, including cis-9, trans-11 C18:2, and a lower n-6/n-3
      ratio than subcutaneous fat. The results from this study demonstrate that dietary
      extruded linseed supplementation of lactating ewes enhances the nutritional
      quality of suckling lamb fat depots such as intramuscular and subcutaneous fats.

PMID- 24334054
TI  - Physicochemical and microbiological characteristics of biltong, a traditional
      salted dried meat of South Africa.
AB  - The microbiological and physicochemical characteristics of several commercial
      beef, kudu and springbok biltong samples from South Africa were assessed in this
      study. Analysis of samples allowed their differentiation into 'dry' and 'moist'
      samples. Dry biltong showed low moisture content (21.5-25.3 g/100 g), a low water
      activity (0.65-0.68) and a high salt content (5.5-7.9 g/100 g), while moist
      biltong showed a higher moisture content (35.1-42.8 g/100 g), a higher water
      activity (0.85 to 0.89) and a lower salt content (3.8-5.6 g/100 g). The pH value
      did not vary significantly between both groups (5.00-6.26). The results showed
      that dry biltong presented a low total plate count (TPC) content, a high level of
      lactic acid bacteria (LAB) and a high level of D-lactic acid as compared to moist
      biltong. These results suggest that dry biltong complies with the standard
      hygienic quality (TPC<7 log cfu/g in agreement with the Food Standards Agency),
      while moist biltong samples generally showed a low content of D-lactic acid and a
      low ratio LAB/TPC.

PMID- 24334056
TI  - Lose dose genistein inhibits glucocorticoid receptor and ischemic brain injury in
      female rats.
AB  - Although acute bolus of genistein treatment has been shown to protect against
      neuronal damage in experimental brain injury animal models, chronic continuous
      low dose treatment of genistein on ischemic brain injury has not been well
      elucidated. In the present study, female rats were received either pure genistein
      (0.1mg/kg/day via osmotic minipumps) or placebo at the time of ovariectomy, and
      transient forebrain ischemia was induced 7days later. Results demonstrated that
      genistein treatment for 14days significantly improved ischemic neuronal survival
      in hippocampal CA1 region of ovariectomized rats. Glucocorticoid receptor (GR) is
      a member of the adrenal steroid hormone receptor, which is highly expressed in
      the rat hippocampus. Activation of the GR plays a critical role in the neuronal
      stress responses, including ischemic brain damage. This study therefore examined
      the potential mechanisms by which genistein regulates GR signaling, including the
      protein distribution and receptor activation in hippocampus following ischemic
      reperfusion (I/R). Results showed that GR expression in the ovariectomized rats
      was excessively increased both in neurons (I/R 6h) and activated microglial cells
      (I/R 7d) in hippocampal CA1 region. Genistein treatment significantly attenuated
      GR induction and the enhanced GR nuclear translocation and DNA-binding capacity.
      The effects of genistein on the GR levels was accompanied with decreased blood
      plasma levels of corticosterone (primary glucocorticoid in rodents) and coupled
      to an E3 ubiquitin ligase Mdm2 targeted proteasomal degradation of GR, because
      genistein treatment could enhance the GR-Mdm2 interaction and the ubiquitination
      level of GR protein. In addition, our results indicated that genistein markedly
      prevented the excessive activation of microglia in CA1 sector. These results
      demonstrate the neuroprotective action of chronic low dose genistein replacement
      against ischemic brain damage, and a potential mechanism associated with the
      inhibition of both neuronal and microglial GR signaling following ischemic
      stress. 

PMID- 24334055
TI  - Genetic deletion of the neuronal glutamate transporter, EAAC1, results in
      decreased neuronal death after pilocarpine-induced status epilepticus.
AB  - Excitatory amino acid carrier 1 (EAAC1 also called EAAT3) is a Na(+)-dependent
      glutamate transporter expressed by both glutamatergic and GABAergic neurons. It
      provides precursors for the syntheses of glutathione and GABA and contributes to
      the clearance of synaptically released glutamate. Mice deleted of EAAC1 are more
      susceptible to neurodegeneration in models of ischemia, Parkinson's disease, and
      aging. Antisense knock-down of EAAC1 causes an absence seizure-like phenotype.
      Additionally, EAAC1 expression increases after chemonvulsant-induced seizures in
      rodent models and in tissue specimens from patients with refractory epilepsy. The
      goal of the present study was to determine if the absence of EAAC1 affects the
      sensitivity of mice to seizure-induced cell death. A chemoconvulsant dose of
      pilocarpine was administered to EAAC1(-/-) mice and to wild-type controls.
      Although EAAC1(-/-) mice experienced increased latency to seizure onset, no
      significant differences in behavioral seizure severity or mortality were
      observed. We examined EAAC1 immunofluorescence 24h after pilocarpine
      administration and confirmed that pilocarpine causes an increase in EAAC1
      protein. Forty-eight hours after induction of seizures, cell death was measured
      in hippocampus and in cortex using Fluoro-Jade C. Surprisingly, there was ~2-fold
      more cell death in area CA1 of wild-type mice than in the corresponding regions
      of the EAAC1(-/-) mice. Together, these studies indicate that absence of EAAC1
      results in either a decrease in pilocarpine-induced seizures that is not
      detectable by behavioral criteria (surprising, since EAAC1 provides glutamate for
      GABA synthesis), or that the absence of EAAC1 results in less pilocarpine/seizure
      induced cell death, possible explanations as discussed. 

PMID- 24334057
TI  - Editor's perspectives - January 2014.

PMID- 24334058
TI  - Reply to Letter: Cardiac arrest prognostic factors in children.

PMID- 24334059
TI  - Synthesis, crystal structure and ab initio/DFT calculations of a derivative of
      dithiophosphonates.
AB  - The compound 2 has been synthesized from the reaction of 2,4-Bis(4-methoxyphenyl)
      1,3,2,4-dithiadiphosphetane-2,4-disulfide and (R)-1-[3,5
      Bis(trifloromethyl)phenyl]ethanol in toluene. The obtained crude dithiophosphonic
      acid 1 has been treated with the excess of N(C2H5)3 to give rise to 2,
      [(+HN(C2H5)3][O-CH3CH-C6H3(CF3)2)(CH3OC6H4)PS2(-)]. The compound 2 has been
      characterized by using the spectroscopic methods such as IR, (1)H, (13)C, (31)P
      NMR and structural analysing method such as X-ray crystallography. It
      crystallizes in the orthorhombic system, whose space group is P212121. It
      consists of a dithiophosphonate bridged methoxyphenyl and
      bis(triflorophenylethyl) groups and a triethylammonium moiety linked by N-H?S and
      C-H?F hydrogen bonds. In the crystal structure, the C17H14F6O2PS2 molecule is
      elongated along the b-axis and stacked along the a-axis. The triethylammonium,
      N(CH2CH3)3, molecule fill in the cavities between the C17H14F6O2PS2 molecule.
      Moreover, ab initio methods based on Hartree-Fock (HF) and Density Functional
      Theory (DFT) calculations with the basis set of 6-31G(d) are also carried out to
      determine the molecular structural properties and to calculate FT-IR and NMR
      spectrum of the compound 2. The experimental results and theoretical calculations
      have been compared, and they are found to be in good agreement.

PMID- 24334060
TI  - Molecular spectroscopic investigation on fractionation-induced changes on
      biomacromolecule of co-products from bioethanol processing to explore protein
      metabolism in ruminants.
AB  - Fractionation processing is an efficient technology which is capable to
      redesign/redevelop a new food or feed product with a specified chemical and
      nutrient profile. This processing technique was able to produce four different
      fractions (called "A", "B", "C", "D" fractions/treatments) with different
      nutrient profile form a co-product of bioethanol processing [wheat dried
      distillers grains with soluble (DDGS)]. To date, there is no study on the effect
      of fractionation processing on inherent molecular structure of different
      fractions and how the processing-induced structural change affect the metabolic
      characteristics of protein and nutrient availability. The objectives of this
      experiment were to: (1) investigate the effect of fractionation processing on
      changes of protein functional groups (amide I, amide II, and their ratio) and
      molecular structure (modeled alpha-helix, beta-sheet, and their ratio), and (2)
      study the relationship between the fractionation processing-induced changes of
      protein molecular structure and nutrients availability as well as the metabolic
      characteristics of protein. The hypothesis of this study was that the
      fractionation processing changes the molecular structure and such changes affect
      the metabolic characteristics of protein. The protein molecular structure
      spectral profile of the fractions A, B, C and D were identified by Fourier
      transform infrared attenuated total reflection spectroscopy (FT/IR-ATR). The
      results showed that the fractionation processing significantly affected the
      protein molecular spectral profiles. The differences in amide I to amide II peak
      area and height ratios were strongly significant (P<0.01) among the treatment
      fractions, ranging from 4.98 to 6.33 and 3.28 to 4.00, respectively. The
      difference in the modeled protein alpha-helix to beta-sheet ratio was also
      strongly significant (P<0.01) among the treatment fractions. Multivariate
      molecular spectral analysis with cluster (CLA) and principal component analyses
      (PCA) showed that there are no clear distinguished clusters and ellipses among
      the fractions (A, B, C and D) in the protein amide I and II region ca. 1726-1485
      cm(-1). The correlation study showed that the modeled alpha-helix to beta-sheet
      ratio tended to have a negative correlation with truly absorbed rumen undegraded
      protein (ARUP(DVE): r=-0.944, P=0.056<0.10) and total truly absorbed protein in
      the small intestine (DVE: r=-0.946, P=0.054<0.10), but there was no correlation
      between the alpha-helix to beta-sheet ratio and the degraded protein balance
      (DPB(OEB): P=0.267<0.10). In conclusion, the fractionation processing changed the
      molecular structural spectral profiles in terms of amide I to II ratio and alpha
      helix to beta-sheet ratio. These changes negatively affected the metabolic
      characteristics of protein and true protein supply. These results indicated that
      spectral features of different fractions could be used as a potential tool to
      predict true protein nutritive value.

PMID- 24334061
TI  - Coordination modes of bidentate lornoxicam drug with some transition metal ions.
      Synthesis, characterization and in vitro antimicrobial and antibreastic cancer
      activity studies.
AB  - The NSAID lornoxicam (LOR) drug was used for complex formation reactions with
      different metal salts like Cr(III), Mn(II), Fe(III) and Ni(II) chlorides and
      Fe(II), Co(II), Cu(II) and Zn(II) borates. Mononuclear complexes of these metals
      are obtained that coordinated to NO sites of LOR ligand molecule. The nature of
      bonding and the stereochemistry of the complexes have been deduced from elemental
      analyses, IR, UV-Vis, (1)H NMR, mass, electronic spectra, magnetic susceptibility
      and ESR spectral studies, conductivity measurements, thermogravimetric analyses
      (TG-DTG) and further confirmed by X-ray powder diffraction. The activation
      thermodynamic parameters are calculated using Coats-Redfern and Horowitz-Metzger
      methods. The data show that the complexes have composition of ML2 type except for
      Fe(II) where the type is [ML3]. The electronic absorption spectral data of the
      complexes suggest an octahedral geometry around the central metal ion for all the
      complexes. The antimicrobial data reveals that LOR ligand in solution show
      inhibition capacity less or sometimes more than the corresponding complexes
      against all the species under study. In order to establish their future potential
      in biomedical applications, anticancer evaluation studies against standard breast
      cancer cell lines (MCF7) was performed using different concentrations. The
      obtained results indicate high inhibition activity for Cr(III), Fe(II) and Cu(II)
      complexes against breast cancer cell line (MCF7) and recommends them for testing
      as antitumor agents. 

PMID- 24334062
TI  - Vibrational structure of n-pi* transition of the UV absorption spectrum of
      acryloyl fluoride in the gas phase.
AB  - UV absorption spectrum of acryloyl fluoride molecule in the gas phase has been
      obtained in the region at 32600-35500 cm(-1) with the purpose of the
      investigation of the hindered internal rotation. The resolved vibrational
      structure of this spectrum consists of 92 absorption bands, each of which
      corresponds to a certain transition from the ground (S0) to excited (S1)
      electronic state. The assignment of all bands has been made. The values
      nu00trans=34831.8 cm(-1) and nu00cis=34679.2 cm(-1) have been determined. Several
      Deslandres Tables (DTs) have been constructed for torsional vibration of s-trans-
      and s-cis-isomers of investigated molecule. The origins in these DTs correspond
      to bands assigned to nu00 and to fundamental frequencies of each isomer in the S0
      and S1 states. These DTs have been used to determine the harmonic frequencies
      omegae, anharmonicity coefficients x11, and frequencies of the torsional
      vibration transitions (0-upsilon) up to high values of the vibrational quantum
      number upsilon of s-trans- and s-cis-isomers in the both electronic states. The
      frequencies of torsional vibrations are nu1(")=116.5cm(-1) for s-trans-isomer and
      nu1(")=101.2 cm(-1) for s-cis-isomer in the S0 state. The frequencies of ones are
      nu1(')=170.4 cm(-1) for s-trans-isomer and nu1(')=139.7 cm(-1) for s-cis-isomer
      in the S1 state. The fundamental vibrational frequencies set has been found for
      isomers in the S0 and S1 states.

PMID- 24334063
TI  - Synthesis, structural and spectroscopic investigations of nanostructured samarium
      oxalate crystals.
AB  - Nanostructured samarium oxalate crystals were prepared via microwave assisted co
      precipitation method. The crystal structure and morphology of the sample were
      analyzed using X-ray powder diffraction, Scanning electron microscopy and
      Transmission electron microscopy. The presence of functional groups is
      ascertained by Fourier transform infrared spectroscopy. Samarium oxalate
      nanocrystals of average size 20 nm were aggregated together to form nano-plate
      structure in sub-microrange. Detailed spectroscopic investigation of the prepared
      phosphor material was carried out by Judd-Ofelt analysis based on the UV-Visible
      NIR absorption spectra and photoluminescence emission spectra. The analysis
      reveals that the transition from energy level (4)G5/2 to (6)H7/2 of Sm(3+) ion
      has maximum branching ratio and the corresponding orange emission can be used for
      display applications.

PMID- 24334064
TI  - Spectroscopic (FT-IR, FT-Raman, 1H, 13C NMR, UV/VIS), thermogravimetric and
      antimicrobial studies of Ca(II), Mn(II), Cu(II), Zn(II) and Cd(II) complexes of
      ferulic acid.
AB  - The molecular structure of Mn(II), Cu(II), Zn(II), Cd(II) and Ca(II) ferulates (4
      hydroxy-3-methoxycinnamates) was studied. The selected metal ferulates were
      synthesized. Their composition was established by means of elementary and
      thermogravimetric analysis. The following spectroscopic methods were used:
      infrared (FT-IR), Raman (FT-Raman), nuclear magnetic resonance ((13)C, (1)H NMR)
      and ultraviolet-visible (UV/VIS). On the basis of obtained results the electronic
      charge distribution in studied metal complexes in comparison with ferulic acid
      molecule was discussed. The microbiological study of ferulic acid and ferulates
      toward Escherichia coli, Bacillus subtilis, Candida albicans, Pseudomonas
      aeruginosa, Staphylococcus aureus and Proteus vulgaris was done. 

PMID- 24334065
TI  - Investigations on luminescence performance of Sm3+ ions activated in multi
      component fluoro-phosphate glasses.
AB  - Different metal oxide based fluoro-phosphate glasses doped with Sm(3+) ions are
      investigated using XRD, SEM with EDS, FTIR, Raman spectra, optical absorption and
      photo-luminescence techniques. These glass matrices have been prepared by
      conventional melt quenching technique. The glassy nature of the present glass
      matrices are confirmed by XRD profiles and SEM photographs. The composition of
      the glasses is checked by EDS. Based on FTIR and Raman spectra, the authors have
      analyzed functional groups that are present in the glass matrices. Judd-Ofelt
      intensity parameters, Omegalambda (lambda=2,4,6) have been evaluated from
      absorption spectra. Radiative parameters such as radiative transition
      probabilities (AR), radiative lifetimes (tauR), integrated absorption cross
      sections (Sigma) and branching ratios (betaR) are calculated using Judd-Ofelt
      intensity parameters. From the photoluminescence spectra, experimental branching
      ratios (betaexp) and stimulated emission cross-sections (sigmaP) for all the
      observed emission transitions are calculated. To investigate luminescence
      potentiality of (4)G5/2->(6)H7/2 emission level of Sm(3+) doped different
      fluorophosphate glasses, experimental radiative lifetimes (tauexp) are obtained
      from decay curve analysis for all glass matrices. Finally, these observed results
      are discussed and compared with the literature data. 

PMID- 24334066
TI  - Structural, electronic, vibrational and NMR spectral analyses of
      [Ru(OAc)(2cqn)2NO] (H2cqn=2-chloro-8-quinolinol) isomers.
AB  - Geometries of three [Ru(OAc)(2cqn)2NO] (H2cqn=2-chloro-8-quinolinol) isomers were
      fully optimized with density functional theory (DFT), and compared with their
      crystal structures. Their electronic spectra, infrared and NMR spectra were also
      calculated at the B3LYP level with Lanl2dz and 6-311G(d,p) as the basis set. And
      good agreement had been achieved between experimental and theoretical values of
      structural parameter, UV-vis absorption and scaled vibration frequency. With the
      gauge independent atomic orbital (GIAO) method, chemical shifts in (1)H and (13)C
      NMR of these isomers were also calculated, which could reasonably match with the
      experimental data. The calculated frontier molecular orbitals suggested that the
      electronic transition from a ligand-based orbital to an antibonding overlap of
      the Ru(d) and pi(*) NO(p) control the photo-induced reactivity of
      [Ru(OAc)(2cqn)2NO] complexes. 

PMID- 24334067
TI  - Relay recognition of Cu2+ and S2- in water by a simple 2-(2'
      aminophenyl)benzimidazole derivatized fluorescent sensor through modulating
      ESIPT.
AB  - A new 2-(2'-aminophenyl)benzimidazole (2-APBI) derivatized fluorescent sensor (L)
      that behaves relay recognition of Cu(2+) and S(2-) in water solution (pH 7.4) has
      been developed. Sensor L displays excited-state intramolecular proton transfer
      (ESIPT) featured two emission bands and performs highly selective and sensitive
      recognition to Cu(2+) through two emissions simultaneous quenching. The on-site
      formed L-Cu(2+) complex exhibits excellent selectivity to S(2-) with fluorescence
      "off-on" response via Cu(2+) displacement approach, which exerts ESIPT recovery.
      Thus, through modulation the ESIPT state of sensor L, relay recognition of Cu(2+)
      and S(2-) in water has been achieved. 

PMID- 24334070
TI  - Comparison of synchronisation and fertility after different modifications of the
      ovsynch protocol in cyclic dairy cows.
AB  - The objectives of this study were to evaluate the effects of (1) double doses of
      PGF2alpha administration or (2) an exogenous progesterone (CIDR) applied
      concurrently with, or (3) the day after, first GnRH of Ovsynch (GnRH-1), on
      synchronisation and fertility during the Ovsynch protocol. All cows (n = 378)
      received the Ovsynch protocol (GnRH-7d-PGF2alpha-56h-GnRH-18h-TAI). The 'OVS'
      group (n = 105) received only the Ovsynch protocol. The 'OVS-PGF' group (n = 118,
      GnRH-7d-PGF2alpha-12h-PGF2alpha-44h-GnRH-18h-TAI) received an extra dose of
      PGF2alpha 12 h later on Day 7. The 'OVS-7CIDR' group (n = 78, GnRH+CIDR-7d
      PGF2alpha-56h-GnRH-18h-TAI) received a CIDR for 7 days between GnRH-1 and
      PGF2alpha. In the 'OVS-6CIDR' group (n = 77, GnRH-24h-CIDR-6d-PGF2alpha-56h-GnRH
      18h-TAI), CIDR was applied one day after GnRH-1 and removed 6 days later. When
      all cows were evaluated, the responses to GnRH-2 were higher (P = 0.005) in cows
      that responded to GnRH-1 (95.4%) compared to the cows that did not respond
      (87.6%). The pregnancy rates at 31 and 62 days for each group were 48.6% and
      42.9% in the OVS, 54.2% and 52.5% in the OVS-PGF, 52.6% and 48.7% in the OVS
      7CIDR, and 55.8% and 49.3% in the OVS-6CIDR groups. Thus, none of the three
      different treatments has an effect on increasing the out-comes of the Ovsynch
      protocol in cyclic lactating dairy cows. 

PMID- 24334068
TI  - Visceral analgesic effect of 5-HT(4) receptor agonist in rats involves the
      rostroventral medulla (RVM).
AB  - The 5-HT(4) receptor agonist tegaserod (TEG) has been reported to modulate
      visceral pain. However, the underlying mechanism remains unknown. The objective
      of the present study was to examine the analgesic mechanism and site of action of
      TEG. In male rats, visceral pain was assessed by measuring visceromotor response
      (VMR) to colorectal distension (CRD). Inflammation was induced by intracolonic
      injection of tri-nitrobenzene sulfonic acid (TNBS). The effect of TEG on the VMR
      was tested by injecting intraperitoneal (i.p.), intrathecal (i.t.),
      intracerebroventricular (i.c.v) or in the rostroventral medulla (RVM). The effect
      of the drug was also tested on responses of CRD-sensitive pelvic nerve afferents
      (PNA) and lumbo-sacral (LS) spinal neurons. Systemic injection of TEG attenuated
      VMR in naive and TNBS-treated rats. Similarly, supraspinal, but not spinal,
      injection of TEG attenuated the VMR. While GR113808, (selective 5-HT(4)
      antagonist) blocked the effect, naloxone (NLX) an opioid receptor antagonist
      reversed the effect of TEG. Although i.t. NLX did not block the inhibitory effect
      of TEG in VMR study, i.t. injection of alpha2-adrenergic receptor antagonist
      yohimbine blocked the effect of TEG when given systemically. While TEG had no
      effect on the responses of CRD-sensitive PNA, it inhibited the responses of CRD
      sensitive LS neurons in spinal intact condition. This inhibition was blocked by
      GR113808, NLX and beta-funaltrexamine (beta-FNA) when injected into the RVM.
      Results indicate that TEG produces analgesia via activation of supraspinal 5
      HT(4) receptors which triggers the release of opioids at supraspinal site, which
      activates descending noradrenergic pathways to the spinal cord to produce
      analgesia.

PMID- 24334071
TI  - Serum total and bone alkaline phosphatase levels and their correlation with serum
      minerals over the lifespan of sheep.
AB  - This study aimed to assess serum total alkaline phosphatase (ALP) and its bone
      isoform (BALP) levels during the ageing and in different physiologic states of
      sheep, in order to expand the knowledge about the variation of these biomarkers
      over the sheep lifespan. Ninety female sheep were divided into nine groups of
      various ages and physiological states (dry, lactation and pregnancy). Serum ALP,
      BALP and mineral levels were determined by commercial immunoassay, molecular
      absorbance spectrophotometry and chemical luminescence for BALP determination.
      Serum ALP and BALP decreased as sheep aged, and no statistically significant
      differences were obtained between ewes in different physiologic states. The
      continuous decline of serum BALP concentration along the sheep lifespan, namely
      in mature and old sheep, is a sign of decreasing bone turnover associated with
      ageing. Serum calcium concentrations increased slightly until 2 years of age and
      then showed a tenuous but statistically significant decrease in mature sheep,
      while serum phosphorus maintained an uninterrupted decrease as sheep matured. The
      knowledge of serum values of bone biomarkers throughout the sheep lifespan may be
      useful in preclinical orthopaedic research studies and for animal science studies
      using sheep. 

PMID- 24334072
TI  - Control of ovulation after prostaglandin treatment by means of ultrasonography
      and effect of the time of ovulation on conception rate in dairy cows.
AB  - Primiparous and multiparous lactating crossbred dairy cows (after Day 40
      postpartum) with a mature corpus luteum (CL) (diameter of >= 17 mm determined by
      ultrasonography) and having a follicle with a diameter of >= 10 mm were treated
      with natural prostaglandin F2alpha (n = 80). Those from the cows that showed
      oestrus within 5 days after treatment were inseminated (Group 1: n = 39). Other
      group of cows showing oestrus without treatment (Group 2: n = 41) were
      inseminated and served as controls. The ovaries of each cow were scanned by
      transrectal ultrasonography from the day of detected oestrus (Day -1p.m.) until
      ovulation, to measure the changes in the areas of the CL and the largest follicle
      and to determine the occurrence of ovulation. Although no significant differences
      were found between the treated and untreated cows in terms of a reduction in the
      area of the corpora lutea and of an increase in the area of the dominant
      follicles, the mean area of these follicles in Group 2 was somewhat greater than
      in Group 1. The highest conception rate was achieved if AI was performed at the
      same day as ovulation occurred in both groups (conception rate in treated group
      was: 62.5%, in untreated group: 66.6%, respectively) between Day 0a.m. to Day
      0p.m.. In Group 1, 54.5% conception rate has been achieved if ovulation occurred
      between Day 0p.m. to Day 1p.m., or 50% between Day 1p.m. to Day 2p.m. after AI,
      and 53.3% and 44.4% in Group 2, respectively. The conception rate for cows that
      ovulated before AI in Group 2 was 25%. No ovulation occurred in 7 cows until Day
      2p.m. after AI and none of them became pregnant. The overall conception rate was
      approximately 50% in both groups, but when the cows had ovulated too early or too
      late relative to the time of AI, the conception rate was significantly lower,
      thus determination of the optimal time for AI is of great practical importance in
      dairy herds. 

PMID- 24334069
TI  - Glutamate spillover drives endocannabinoid production and inhibits GABAergic
      transmission in the Substantia Nigra pars compacta.
AB  - Endocannabinoids (eCBs) modulate synaptic transmission in the brain, but little
      is known of their regulatory role in nigral dopaminergic neurons, and whether
      transmission to these neurons is tonically inhibited by eCBs as seen in some
      other brain regions. Using whole-cell recording in midbrain slices, we observed
      potentiation of evoked IPSCs (eIPSCs) in these neurons after blocking CB1
      receptors with rimonabant or LY-320,135, indicating the presence of an eCB tone
      reducing inhibitory synaptic transmission. Increased postsynaptic calcium
      buffering and block of mGluR1 or postsynaptic G-protein coupled receptors
      prevented this potentiation. Increasing spillover of endogenous glutamate by
      inhibiting uptake attenuated eIPSC amplitude, while enhancing the potentiation by
      rimonabant. Group I mGluR activation transiently inhibited eIPSCs, which could be
      prevented by GDP-beta-S, increased calcium buffering or rimonabant. We explored
      the possibility that the dopamine-derived eCB N-arachidonoyl dopamine (NADA) is
      involved. The eCB tone was abolished by preventing dopamine synthesis, and
      enhanced by l-DOPA. It was not detected in adjacent non-dopaminergic neurons.
      Preventing 2-AG synthesis did not affect the tone, while inhibition of NADA
      production abolished it. Quantification of ventral midbrain NADA suggested a
      basal level that increased following prolonged depolarization or mGluR
      activation. Since block of the tone was not always accompanied by attenuation of
      depolarization-induced suppression of inhibition (DSI) and vice versa, our
      results indicate DSI and the eCB tone are mediated by distinct eCBs. This study
      provides evidence that dopamine modulates the activity of SNc neurons not only by
      conventional dopamine receptors, but also by CB1 receptors, potentially via NADA.

PMID- 24334073
TI  - Cell cycle analysis and interspecies nuclear transfer of cat cells treated with
      chemical inhibitors.
AB  - This study investigated the effect of chemical inhibitors on the cell-cycle
      synchronisation in cat fibroblast cells and evaluated the development of
      interspecies embryos reconstructed from cat donor cells and enucleated bovine
      oocytes. Cat fibroblast cells were treated with 15 MUg/mL roscovitine or 0.05
      MUg/mL deme-colcine prior to cell cycle analysis and nuclear transfer. The
      percentage of cat fibroblast cells arrested at the G0/G1 phase in the roscovitine
      group was similar to that in the control group without any treatment. The
      percentage of cells arrested at the G2/M phase was significantly higher in the
      demecolcine group than in the control group. The fusion rate of interspecies
      couplets was significantly greater in the roscovitine group than in the control
      group. Most embryos stopped the development at the 2- or 4-cell stage, and none
      developed into blastocysts. Chemical inhibitor-induced donor cell cycle
      synchronisation did not overcome developmental arrest in interspecies cloned
      embryos. 

PMID- 24334074
TI  - Heparin binding analysis of boar sperm and its relation with farrowing capacity.
AB  - New methods for the evaluation of semen quality according to in vivo reproductive
      data are useful tools for identifying boars of lower fertility among individuals
      with standard semen parameters. In this study, indirect fluorescence microscopy
      was used to evaluate the heparin binding site distribution upon capacitation of
      sperm from eight boars arbitrarily distributed into Groups I and II according to
      differential farrowing rates (Group I: >= 70%, Group II: < 70%). Additionally,
      the ability of sperm to bind to solubilised zona pellucida (ZP) was assayed in
      the presence or absence of heparin. Samples of two individuals of Group II showed
      lower percentage of B pattern in relation to other individuals (P < 0.001). The
      number of spermatozoa attached to ZP after 2 h of incubation in capacitating
      conditions with heparin was significantly lower than in its absence (P < 0.0001).
      These results suggest that heparin binding site distribution concerning
      capacitation may be indicative of the availability of proteins involved in the
      fertilisation process, specifically at the initial sperm-oocyte recognition.
      Differences in heparin binding site dynamics during capacitation may help
      identify a subpopulation of individuals with lower fertilising capacity and
      normal spermiogram, which is particularly useful at high-production
      establishments. 

PMID- 24334075
TI  - Effects of skim-milk supplementation on the quality and penetrating ability of
      boar semen after long-term preservation at 15  degrees C.
AB  - This study investigated the effects of skim-milk supplementation on the quality
      and penetrating ability of boar semen preserved at 15  degrees C. When boar semen
      samples were preserved in Modified Modena extender supplemented with various
      concentrations (0, 7.5, 15, 30 and 50 mg/mL) of skim milk powder at 15  degrees C
      for 4 weeks, higher sperm motility and viability were observed in the case of 7.5
      mg/mL skim-milk supplementation compared with the control group (0 mg/mL) during
      the preservation (P < 0.05). When in vitro matured oocytes were co-incubated with
      boar sperm that had been preserved in Modified Modena extender with three
      different concentrations (0, 7.5 or 15 mg/mL) of skim milk powder at 15  degrees
      C for two weeks, there were no apparent effects of skim-milk supplementation on
      the rates of fertilisation and development to blastocysts of oocytes after co
      incubation. However, the monospermic fertilisation rate of sperm preserved with
      15 mg/mL skim milk powder was higher (P < 0.05) than that of fresh non-preserved
      sperm, but did not differ among the preservation groups. The results indicate
      that the supplementation of Modified Modena extender with 7.5 mg/mL skim milk
      powder improves the motility and viability, but not the penetrating ability, of
      sperm after liquid preservation for at least two weeks. 

PMID- 24334076
TI  - Serum vascular endothelial growth factor concentration in dogs diagnosed with
      chronic superficial keratitis.
AB  - The objective of this study was to measure the vascular endothelial growth factor
      (VEGF) levels in dogs diagnosed with chronic superficial keratitis (CSK). The
      study was performed on 25 German shepherds (14 males and 11 females, aged between
      3 and 11 years). The VEGF levels were determined in blood serum using
      commercially available enzyme-linked immunosorbent assay (ELISA; Quantikine
      Canine VEGF Immunoassay, R&D Systems). The test group of affected German
      shepherds was subdivided into two subgroups, based on the area of corneal
      neovascularisation. The first subgroup (9 patients) comprised dogs with
      neovascularisation observed in 1 to 2 quadrants of the right and left cornea,
      while the second subgroup (16 patients) comprised dogs with neovascularisation
      observed in 3 to 4 quadrants of the right and left cornea. The control group
      comprised 12 clinically healthy German shepherds (7 males and 5 females, aged
      between 3 and 9 years). The results were then statistically analysed by the Mann
      Whitney test. The study indicated that the median serum VEGF concentration in
      healthy dogs was 14.9 pg/mL. The VEGF level observed in sick German shepherds was
      elevated (19.5 pg/mL) as compared to the values found in healthy dogs; however, a
      statistically significant increase in VEGF concentration, as compared to the
      values observed in healthy dogs, was only noted in the first subgroup, where the
      median VEGF concentration was 22.0 pg/mL. Elevated serum VEGF concentration was
      observed in German shepherds diagnosed with CSK. A statistically significant
      increase in VEGF levels was observed in dogs in the first stage of the disease,
      i.e. the early stage of neovascularisation. 

PMID- 24334077
TI  - Body fat distribution and metabolic consequences - Examination opportunities in
      dogs.
AB  - The relationship between metabolic disorders and the distribution of fat in
      different body regions is not clearly understood in humans. The aim of this study
      was to develop a suitable method for assessing the regional distribution of fat
      deposits and their metabolic effects in dogs. Twenty-five dogs were subjected to
      computed tomographic (CT) imaging and blood sampling in order to characterise
      their metabolic status. The different fat areas were measured on a cross
      sectional scan, and the animals' metabolic status was evaluated by measuring
      fasting glucose, insulin and leptin levels. The volume of visceral adipose tissue
      is the main determinant of leptin levels. The correlation of visceral fat volume
      and leptin concentration was found to be independent of insulin levels or the
      degree of insulin resistance. There was a positive correlation between the
      visceral to subcutaneous fat volume ratio and serum insulin concentration, and a
      similar trend was observed in the relationship of fat ratio and insulin
      resistance. The distribution of body fat essentially influences the metabolic
      parameters in dogs, but the effects of adiposity differ between humans and dogs.
      The findings can facilitate a possible extrapolation of results from animal
      studies to humans with regard to the metabolic consequences of different obesity
      types. 

PMID- 24334078
TI  - First detection of circovirus-like sequences in amphibians and novel putative
      circoviruses in fishes.
AB  - The negative samples of a collection, established originally for seeking new
      adeno- and herpesviruses in lower vertebrates, were screened for the pres-ence of
      circoviruses by a consensus nested PCR targeting the gene coding for the
      replication-associated protein. Six fish samples representing five species,
      namely asp (Aspius aspius), roach (Rutilus rutilus), common bream (Abramis
      brama), round goby (Neogobius melanostomus) and monkey goby (Neogobius
      fluviatilis), as well as three frog samples were found positive for circoviral
      DNA. Sequence analysis of the amplicons indicated the presence of three novel
      putative circo-like viruses and a circovirus in Hungarian fishes and one novel
      circovirus in a common toad (Bufo bufo), and another one in a dead and an alive
      specimen of green tree frog (Litoria caerulea), respectively. In phylogeny
      reconstruction, the putative bream circovirus clustered together with
      circoviruses discovered in other cyprinid fishes recently. Three other piscine
      circoviral sequences appeared closest to sequences derived from different
      environmental samples. Surprisingly, the nucleotide sequence derived from two
      fish samples (a bream and a monkey goby) proved to be from porcine circovirus 2
      (PCV2), almost identical to a sequence detected in Sweden previously. This is the
      first report on the detection of PCV2 in fish and circoviral DNA in amphibian
      hosts. 

PMID- 24334079
TI  - Expression and cellular distribution of cyclin-dependent kinase 4 (Cdk4) and
      connexin 43 (Cx43) in porcine oocytes before and after in vitro maturation.
AB  - It is recognised that connexin 43 (Cx43) and cyclin-dependent kinase 4 (Cdk4) are
      involved in the cumulus cell-oocyte communication via gap junctions and the
      control of cell cycle progress. However, little is known about their mRNA
      expression pattern and encoded proteins distribution in porcine oocytes during in
      vitro maturation (IVM). Cumulus-oocyte complexes (COCs) were collected from 31
      puberal crossbred Landrace gilts and analysed for their Cdk4 and Cx43 mRNA
      expression using RQ-PCR and for the respective protein expression by confocal
      microscopic observations. An increased Cdk4 and Cx43 mRNA expression was found in
      oocytes after IVM (P < 0.001 and P < 0.05, respectively). Confocal microscopic
      observations revealed a significant increase of Cdk4 protein expression in the
      cytoplasm of oocytes during the maturation process. The localisation of Cx43
      changed from zona pellucida before to cytoplasm of oocytes after IVM. It is
      supposed that the increased expression of Cdk4 and Cx43 mRNA in oocytes after IVM
      is linked with the accumulation of a large amount of templates during the process
      of oocyte maturation. The translocation especially of Cx43 from the zona
      pellucida into the cytoplasm may be associated with a decrease in gap junction
      activity in fully grown porcine oocytes. Both Cdk4 and Cx43 can be used as
      'checkpoints' of oocyte maturation. 

PMID- 24334080
TI  - Characterisation of Pseudomonas aeruginosa related to bovine mastitis.
AB  - Pseudomonas aeruginosa is one of the causative pathogens of bovine mastitis. Most
      P. aeruginosa strains possess the type III secretion system (TTSS), which may
      increase somatic cell counts (SCCs) in milk from mastitis-affected cows.
      Moreover, most of P. aeruginosa cells can form biofilms, thereby reducing
      antibiotic efficacy. In this study, the presence and effect of TTSS-related
      genotypes on increase of SCCs among 122 P. aeruginosa isolates obtained from raw
      milk samples from mastitis-affected cows and their antibiotic susceptibility at
      planktonic and biofilm status were investigated. Based on the presence of TTSS
      related genes a total of 82.7% of the isolates were found to harbour exoU and/or
      exoS genes, including the invasive (exoU-/exoS+, 69.4%), cytotoxic (exoU+/exoS-,
      8.3%) and cytotoxic/invasive strains (exoU+/ exoS+, 5.0%). Milk containing exoS
      positive isolates had higher SCCs than those containing exoS-negative isolates.
      The majority of isolates showed gentamicin, amikacin, meropenem and ciprofloxacin
      susceptibility at planktonic status. However, the susceptibility was decreased at
      the biofilm status. Based on minimum biofilm eradication concentration
      (MBEC)/minimum inhibitory concentration (MIC) ratios, the range of change in
      antibiotic susceptibility varied widely depending on the antibiotics (from >= 3.1
      fold to >= 475.0-fold). In conclusion, most P. aeruginosa isolates studied here
      had a genotype related to increase in SCCs. The efficiency of antibiotic therapy
      against P. aeruginosa-related bovine mastitis could be improved by analysing both
      the MBEC and the MIC of isolates. 

PMID- 24334081
TI  - A comparison of the concentrations of energy-balance-related variables in jugular
      and mammary vein blood of dairy cows with different milk yield.
AB  - The aim of this study was to compare the concentrations of blood variables
      obtained simultaneously from the jugular and mammary veins of dairy cows. Eighty
      Holstein cows were divided into four equal groups: dry, low- (LY), medium- (MY)
      and high-yielding (HY). Blood insulin, glucose, non-esterified fatty acid (NEFA),
      beta-hydroxybutyrate (BHBA) and urea concentrations were measured. The jugular
      and mammary vein (J/M) ratio between concentrations of each variable was
      calculated. Differences between the groups of cows in concentrations of variables
      in the jugular vein were not in accordance with those obtained for the mammary
      vein. J/M values for insulin and glucose concentrations were above 1.0 in all
      groups of cows. The ratios for NEFA and BHBA concentrations were under or equal
      to 1.0 in dry and LY cows but above 1.0 in the MY and HY groups, indicating that
      in MY and HY cows those metabolites are apparently utilised by the mammary gland.
      J/M values for urea were above 1.0 in dry and LY cows but less than 1.0 in groups
      MY and HY, indicating that in the latter case urea is apparently released by the
      mammary gland. In conclusion, J/M for NEFA, BHBA and urea may be useful for
      estimation of the critical point when the mammary gland receives insufficient
      energy precursors for its current activity. 

PMID- 24334082
TI  - Development of a novel immunoperoxidase monolayer assay for detection of swine
      Hepatitis E virus antibodies based on stable cell lines expressing the ORF3
      protein.
AB  - Hepatitis E virus (HEV) strains are classified into 4 genotypes by nucleotide
      sequencing. Genotypes 3 and 4 infect humans and animals via HEV-contaminated food
      or water. HEV RNA was detected by PCR and antibodies were detected by ELISA.
      Since human studies showed that HEV IgG antibodies in sera can persist for
      extended periods, diagnosis of HEV infection in swine or humans is mainly based
      on serological detection using commercial ELISA kits. However, there is no
      supplemental method to verify ELISA results. Hence, we developed a novel method
      used for mutual correction of these common processes. Here, a modified stable
      HepG2 cell line was transfected with pcDNA3.1-ORF3 to express the swine HEV ORF3
      protein. Based on this cell line, a novel immunoperoxidase monolayer assay (IPMA)
      was developed to detect antibodies against HEV. The results show that this method
      has good specificity, sensitivity and repeatability. When used to investigate 141
      porcine serum samples, the IPMA had a coincidence rate of 92.2% with a commercial
      ELISA kit. The established IPMA described herein is valuable as a supplemental
      method to ELISA and can differentiate infections by HEV and other viruses. 

PMID- 24334083
TI  - Mosaic arthroplasty of the medial femoral condyle in horses - An experimental
      study.
AB  - One Arabian and 5 Hungarian half-bred horses were used to study the macroscopic
      and microscopic survival of autologous osteochondral grafts in the weight-bearing
      surface of the medial femoral condyle (MFC). Grafts were harvested from the
      cranial surface of the medial femoral trochlea (MFT) under arthroscopic control.
      Three of them were transplanted into the weight-bearing surface of the
      contralateral MFC using an arthrotomy approach. Three months later this
      transplantation procedure was repeated on the opposite stifle joints in the same
      animals, but at that time transplantation was performed arthroscopically. Follow
      up arthroscopy was carried out 12 months after the first operations, and biopsies
      were taken from both the recipient and the donor sites for histological
      examination. During follow-up arthroscopy, the transplanted areas looked
      congruent and smooth. Microscopically, the characteristics of hyaline cartilage
      were present in 5 out of the 10 biopsies examined; however, in the other half of
      biopsies glycosaminoglycan (GAG) loss and change in the architecture of the
      transplanted cartilage was observed. In a 16-year-old horse, all grafts broke
      during harvesting, and thus transplantation was not performed. No radiological
      signs of osteoarthritic changes were detected 9 to 12 months after the operations
      in the donor and recipient joints. Clinically, no lameness or effusion was
      present three months after the transplantations. 

PMID- 24334084
TI  - Skin and skeletal system lesions of european pond turtles (Emys orbicularis) from
      natural habitats.
AB  - Water pollution is known to play an important role in the pathogenesis of
      plastron, carapace and skin diseases of turtles. In this study, a total of 150
      European pond turtles (Emys orbicularis) of different age and both sexes,
      originating from natural habitats in Serbia, were examined for morphological
      changes of the skin, plastron, carapace and skeletal system. The turtles were
      taken out from their natural habitats in Lake Ludas, Lake Palic and Lake
      Tresetiste. After artificial hibernation, they were subjected to detailed
      examination, sampled and treated, and finally returned into their natural
      habitat. Biopsies from the skin and shell were subjected to histopathological
      examination and microbiological analysis. X-ray scanning was also performed to
      detect changes in the skeletal system. Macroscopic changes of the skin, most
      frequently degenerative, inflammatory or neoplastic diseases, were diagnosed in
      49.33% of the turtles examined. Dermatitis of different origin and form was the
      most prominent histopathological finding (28.00%). In the plastron, inflammatory
      and degenerative processes were frequently found. Osteopathy and mechanical
      injuries were the dominant findings. Macroscopic changes of the plastron,
      carapace and skeletal system were diagnosed in 67.33% of the turtles examined.
      Using X-ray scanning, generalised osteopathy, anomalies and malformations of
      different aetiology were also diagnosed on the tail and legs. Microbiological
      examinations showed the presence of a variety of bacterial and fungal agents,
      either primary pathogens or potential polluters, which invaded the skin and
      shell, or were present in cloacal swab samples. Bacterial infection was diagnosed
      in 76.66% of the turtles, first of all in those with skin and shell necrosis.
      Mycoses were diagnosed in 33.33% of the animals. 

PMID- 24334085
TI  - Macroscopic and histological characteristics of fluid-filled ovarian structures
      in dairy cows.
AB  - The primary objective of this study was to use macroscopic and histological
      features of corpora lutea with a cavity and anovulatory cystic ovarian
      structures, present in 90 pairs of abattoir-derived dairy cow ovaries, as the
      basis to clarify the nomenclature of ovarian structures. Excluding
      morphologically normal ovarian fol-licles (antrum < 2 cm, wall < 1 mm), there
      were 27 fluid-filled ovarian structures. Ovulatory structures > 16 mm in diameter
      were designated as Group A (cavity <= 10 mm and wall > 10 mm) or Group B (cavity
      > 10 mm and wall < 10 mm). The volume of luteal tissue was less (P < 0.05) in
      Group B than in Group A, whereas that of a solid corpus luteum (CL) was
      intermediate (least square means +/- SEM: 72 +/- 1.92, 11.22 +/- 1.57 and 5.84 +/
      1.92 cm3, respectively). There was a greater proportion (P < 0.05) of small
      luteal cells in Group B compared to a solid CL, whereas Group A was intermediate
      (58.6 +/- 5.3, 37.4 +/- 5.3 and 44.0 +/- 4.4%, respectively). Connective tissue
      was thicker (P < 0.05) in Group B than in Group A (295.4 +/- 46.9 vs. 153.9 +/-
      38.2 MUm). Based on the above-mentioned characteristics and differences, Groups A
      and B were designated as a CL with a cavity and a cystic CL, respectively.
      Furthermore, there were three groups of anovulatory ovarian structures.
      Structures in Group C were termed persistent/anovulatory follicles (overall
      diameter and wall thickness <= 20 and 1-3 mm, respectively). Finally, Groups D
      and E were designated as a follicle-fibrous cyst and a follicle-luteinised cyst
      (based on histological structure) for anovulatory structures with an overall
      diameter and wall thickness of >= 20 and <= 3 mm, and >= 20 and >= 3 mm,
      respectively. 

PMID- 24334086
TI  - Survival of porcine reproductive and respiratory syndrome virus in fresh pork.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the
      most economically important diseases of pigs. Transmission of PRRS virus has been
      reported through many routes, with aerosol route being the most predominant.
      There may also be a potential risk of transmission through contami-nated pork,
      but this has never been investigated. The purpose of this study was to
      experimentally contaminate fresh pork with three different concentrations of
      PRRSV and to study virus survival at ambient (25  degrees C), refrigerated (4 
      degrees C), and frozen (-20  degrees C) temperatures. Concentrations of virus
      representing natural infectivity level and 'worst case scenario' were studied.
      The virus was detected in fresh pork at all three virus concentrations for up to
      48 h at ambient temperature. At 4  degrees C, the virus survived for 6 days in
      pork inoculated with the higher virus concentration and for 3 days in pork
      inoculated at the lower concentration. At frozen temperature, PRRSV was detected
      for up to 60 days in pork inoculated at the higher concentration and for 7 days
      in pork inoculated at the lower concentration. These results suggest that fresh
      pork has the potential to be a vehicle for virus dissemination depending upon
      temperature and time of storage. 

PMID- 24334087
TI  - Progesterone improves porcine in vitro fertilisation system.
AB  - In an effort to improve the quality of in vitro produced porcine embryos, the
      effect of progestagens - progesterone analogues - on the in vitro developmental
      competence of porcine oocytes was studied. A total of 1421 in vitro matured
      oocytes, from 4 replicates, were inseminated with frozen-thawed spermatozoa.
      Progestagens were added to late maturation and embryo cultures (10 IU/ml).
      Fertilisation success (pre-maturation, penetration, monospermy and efficiency)
      and nuclear maturation were evaluated. There were no differences among
      prematuration rates between groups (P = 0.221). Penetration rates were higher (P
      < 0.001) in the presence of progestagens (75.0%) as compared to the control
      (51.7%). However, no differences were observed in monospermy percentages (P =
      0.246). The results indicated that supplementation with progestagens increased
      the efficiency of the in vitro fertilisation system (P < 0.001). An additional
      beneficial effect was observed in nuclear maturation with progestagens (P =
      0.035). In summary, progestagen supplementation is an important factor to improve
      the in vitro fertilisation procedure. 

PMID- 24334088
TI  - Expression of claudins in the normal canine gastric mucosa.
AB  - The aim of the present study was to investigate the expression pattern of claudin
      1, -2, -3, -4, -5, -7, -8, -10 and -18 in the intact fundic and pyloric gastric
      mucosa of dogs. Intense, linear, membranous claudin-18 positivity was detected in
      the surface gastric cells and in the epithelial cells of the gastric glands both
      in the fundic and pyloric stomach regions. The mucous neck cells in the apical
      part of the glands, furthermore the parietal cells and chief cells of the basal
      part of the gland were all positive for claudin-18, in the same way as the
      enteroendocrine cells. Cells of the basal part of the pyloric glands showed
      intense, linear, membranous claudin-2 positivity, but cells of the superficial
      portion of these glands and the surface gastric cells in this region were claudin
      2 negative. Fibroblasts, endothelial cells, lymphocytes of the propria layer,
      smooth muscle cells and vegetative neurons were all negative for claudin-2. All
      gastric epithelial cells were negative for claudin-1, -3, -4, -5, -6, -7, -8 and 
      10. The endothelial cells of the propria layer had intense claudin-5 positivity.
      We assume that claudin-18 forms a paracellular barrier against gastric acid in
      the healthy canine stomach, in the same way as in mice. 

PMID- 24334089
TI  - Data on the parasitological status of golden jackal (Canis aureus L., 1758) in
      Hungary.
AB  - In Hungary, twenty Canis aureus individuals were submitted to parasitological
      examinations in 2010-2012. Two Coccidia: Cystoisospora canis (15%) and Toxoplasma
      type oocysts (5%), one Trematoda: Alaria alata (10%), six Cestoda: Mesocestoides
      lineatus (20%), Echinococcus granulosus (10%), Dipylidium caninums (5%), Taenia
      hydatigena (15%), Taenia pisiformis (20%), Taenia crassiceps (40%), and nine
      Nematoda: Angiostrongylus vasorum (10%), Crenosoma vulpis (30%), Capillaria
      aerophila (5%), Toxocara canis (20%), Toxascaris leonina (15%), Trichuris vulpis
      (10%), Ancylostoma caninum (45%), Uncinaria stenocephala (40%), Capillaria plica
      (45%) have been identified. Angiostronglyus vasorum has been reported from
      carnivores in Europe, Africa, South America and North America. The helminth A.
      vasorum or French heartworm is a metastrongylid nematode, widely distributed in
      Western Europe, that infects the pulmonary arterial tree of dogs, various species
      of foxes, wolves, Eurasian badgers, coyotes and stoats. To our knowledge, this is
      the first report of natural A. vasorum infection in golden jackal. 

PMID- 24334090
TI  - Cryptosporidium parvum genotype IIa and Giardia duodenalis assemblage A in
      Mytilus galloprovincialis on sale at local food markets.
AB  - To date, there has been no study to establish the genotypic or subgenotypic
      identities of Cryptosporidium and Giardia in edible shellfish. Here, we explored
      the genetic composition of these protists in Mytilus galloprovincialis
      (Mediterranean mussel) purchased from three markets in the city of Foggia, Italy,
      from May to December 2012. Samples from the digestive glands, gills and
      haemolymph were tested by nested PCR, targeting DNA regions within the 60 kDa
      glycoprotein (gp60) gene of Cryptosporidium, and the triose-phosphate isomerase
      (tpi) and beta-giardin genes of Giardia. In total, Cryptosporidium and Giardia
      were detected in 66.7% of mussels (M. galloprovincialis) tested. Cryptosporidium
      was detected mostly between May and September 2012. Sequencing of amplicons
      showed that 60% of mussels contained Cryptosporidium parvum genotype IIa
      (including subgenotypes A15G2R1, IIaA15G2 and IIaA14G3R1), 23.3% Giardia
      duodenalis assemblage A, and 6.6% had both genetic types. This is the first
      report of these types in fresh, edible shellfish, particularly the very commonly
      consumed M. galloprovincialis from highly frequented fish markets. These genetic
      types of Cryptosporidium and Giardia are known to infect humans and thus likely
      to represent a significant public health risk. The poor observance of hygiene
      rules by vendors, coupled to the large numbers of M. galloprovincialis sold and
      the eating habits of consumers in Italy, call for more effective sanitary
      measures pertaining to the selling of fresh shellfish in street markets.

PMID- 24334091
TI  - Performance of two potential probiotic Lactobacillus strains from the olive
      microbiota as starters in the fermentation of heat shocked green olives.
AB  - The performance of two potential probiotic Lactobacillus strains from olive
      microbiota, namely L. pentosus B281 and L. plantarum B282 was assessed as starter
      cultures in Spanish-style fermentation of heat shocked green olives cv.
      Halkidiki. Two different initial salt levels were studied, 10% (w/v) and 8% (w/v)
      NaCl, and the brines were inoculated with (a) L. pentosus B281, (b) L. plantarum
      B282, and (c) a mixture of both strains. A spontaneous fermentation was also
      taken into account as control treatment. Prior to brining, olives were heat
      shocked at 80  degrees C for 10 min to reduce the level of the indigenous
      microbiota on olive drupes and facilitate the dominance of the inoculated
      cultures. Microbiological, physicochemical and sensory analyses were conducted
      throughout fermentation. The composition of LAB population and the evolution of
      added inocula were assessed by Pulsed Field Gel Electrophoresis (PFGE). The final
      population of LAB was maintained above 6 log cycles in olive flesh. Both L.
      pentosus B281 and L. plantarum B282 were able to dominate over indigenous LAB,
      albeit strain B281 exhibited higher recovery percentages (100 or 94.7% for B281
      and 58.8% or 55.0% for B282 in 10% or 8% NaCl, respectively). L. pentosus B281
      also dominated over L. plantarum B282, when the two strains were co-inoculated in
      olive fermentations. The sensory assessment showed higher preference for
      inoculated fermentations of L. pentosus and L. plantarum separately in 8% NaCl,
      followed by the L. plantarum in 10% NaCl. The present study showed that probiotic
      strains L. pentosus B281 and L. plantarum B282, may offer a great potential for
      use as functional starter cultures in olive fermentation and deliver a promising
      probiotic food to the consumer.

PMID- 24334092
TI  - The gene PatG involved in the biosynthesis pathway of patulin, a food-borne
      mycotoxin, encodes a 6-methylsalicylic acid decarboxylase.
AB  - Patulin is a mycotoxin produced by fungal genera such as Aspergillus, Penicillium
      and Byssochlamys. It induces neurological, gastrointestinal and immunological
      effects, which is why patulin belongs to a short list of mycotoxins whose level
      in food is regulated in many countries around the world. Recently, a cluster
      gathering 15 genes involved in the biosynthesis of patulin has been identified in
      Aspergillus clavatus, but so far, only 4 genes encoding 6-methylsalicylic acid
      synthase, m-cresol hydroxylase, m-hydroxybenzyl alcohol hydroxylase and
      isoepoxydon dehydrogenase have been characterized. Previous studies have shown
      the involvement of a decarboxylase in the transformation of 6-methylsalicylic
      acid, the first stable patulin precursor, into m-cresol. In this study a putative
      decarboxylase gene, PatG, was identified in the genome sequence of A. clavatus.
      This gene is located near two P450 cytochrome genes PatH and PatI responsible
      respectively for the hydroxylation of m-cresol and m-hydroxybenzyl alcohol. This
      decarboxylase encoded by PatG (ACLA_093620) consists of 325 amino acids. The
      search for putative conserved domain revealed that the gene product belongs to
      the AminoCarboxyMuconate Semialdehyde Decarboxylase (ACMSD) related protein
      family. This family includes decarboxylases such as the gamma-resorcylate
      decarboxylase or o-pyrocatechuate decarboxylase. The substrates of these enzymes
      display strong structural similarities with 6-methylsalicylic acid. PatG was
      strongly expressed during patulin production whereas it was very weakly expressed
      in non-patulin permissive conditions. The coding sequence was used to enable
      heterologous expression of functional enzymes in Saccharomyces cerevisiae. The
      presence of decarboxylase was confirmed by Western blot. The bioconversion assays
      showed that PATG catalyzed the decarboxylation of 6-methylsalicylic acid into m
      cresol. These results confirm for the first time that 6-methylsalicylic acid is
      the substrate for PATG, the 6-methylsalicylic acid decarboxylase. With this
      study, the four genes involved in the four first steps of patulin biosynthesis
      pathway (acetate->gentisyl alcohol) are now identified. 

PMID- 24334093
TI  - Evolution of microbiological and chemical parameters during red wine making with
      extended post-fermentation maceration.
AB  - The aim of the present work was to investigate the microbiological, chemical, and
      sensory characteristics of red wine subjected to post-fermentation maceration
      that was extended to 90 days. For this purpose, the 'Aglianico di Taurasi' grape
      was used as a case study. The total yeast concentration increased until day 40 of
      maceration and decreased thereafter, whereas the concentration of lactic acid
      bacteria slightly increased. Dekkera/Brettanomyces spp. and acetic acid bacteria
      were not detected. The yeast community was composed of Saccharomyces cerevisiae,
      Zygosaccharomyces bisporus, Metschnikowia pulcherrima, Hanseniaspora
      guilliermondii, Hanseniaspora uvarum, Pichia guilliermondii, Aureobasidium
      pullulans and Debaryomyces carsonii. Nine S. cerevisiae strains were detected at
      high levels at different times of maceration. The results of all the conventional
      chemical analyses of the wines were in agreement with the regulations of
      commercial production and, interestingly, the changes in terms of concentration
      demonstrated the presence of yeast and LAB populations that were not only alive
      but also in a metabolically active state until day 90 of maceration. The alcohol
      and glycerol contents slightly increased until day 90. The concentrations of
      malic acid decreased, whereas those of lactic acid slightly increased throughout
      the maceration process. Furthermore, different durations of maceration resulted
      in significant differences in the total polyphenol content, which was higher at
      40-50 days. The main phenolic compounds were benzoic and cinnamic acids and
      catechins. Interestingly, the highest ratio between (+)-catechin and (-)
      epicatechin was found on day 40. In addition, the highest antioxidant activity
      was observed between days 40 and 50. The concentration of volatile organic
      compounds, which were mainly represented by alcohols, increased until the end of
      the maceration process. Sensory analysis revealed that samples that were
      subjected to maceration for a long period of time showed the highest odour and
      taste complexity and no off-odours and/or off-flavours were detected. These data
      confirmed that extending post-fermentation maceration to 90 days has no negative
      impact on the microbiological, chemical and sensory composition of wines, but
      affects the polyphenol content and potential health benefits of the resulting
      wine.

PMID- 24334094
TI  - Inactivation of human norovirus using chemical sanitizers.
AB  - The porcine gastric mucin binding magnetic bead (PGM-MB) assay was used to
      evaluate the ability of chlorine, chlorine dioxide, peroxyacetic acid, hydrogen
      peroxide, and trisodium phosphate to inactivate human norovirus within 10% stool
      filtrate. One-minute free chlorine treatments at concentrations of 33 and 189 ppm
      reduced virus binding in the PGM-MB assay by 1.48 and 4.14 log10, respectively,
      suggesting that chlorine is an efficient sanitizer for inactivation of human
      norovirus (HuNoV). Five minute treatments with 5% trisodium phosphate (pH~12)
      reduced HuNoV binding by 1.6 log10, suggesting that TSP, or some other high pH
      buffer, could be used to treat food and food contact surfaces to reduce HuNoV.
      One minute treatments with 350 ppm chlorine dioxide dissolved in water did not
      reduce PGM-MB binding, suggesting that the sanitizer may not be suitable for
      HuNoV inactivation in liquid form. However a 60-min treatment with 350 ppm
      chlorine dioxide did reduce human norovirus by 2.8 log10, indicating that
      chlorine dioxide had some, albeit limited, activity against HuNoV. Results also
      suggest that peroxyacetic acid has limited effectiveness against human norovirus,
      since 1-min treatments with up to 195 ppm reduced human norovirus binding by <1
      log10. Hydrogen peroxide (4%) treatment of up to 60 min resulted in minimal
      binding reduction (~0.1 log10) suggesting that H2O2 is not a good liquid
      sanitizer for HuNoV. Overall this study suggests that HuNoV is remarkably
      resistant to several commonly used disinfectants and advocates for the use of
      chlorine (sodium hypochlorite) as a HuNoV disinfectant wherever possible.

PMID- 24334095
TI  - IPMP 2013--a comprehensive data analysis tool for predictive microbiology.
AB  - Predictive microbiology is an area of applied research in food science that uses
      mathematical models to predict the changes in the population of pathogenic or
      spoilage microorganisms in foods exposed to complex environmental changes during
      processing, transportation, distribution, and storage. It finds applications in
      shelf-life prediction and risk assessments of foods. The objective of this
      research was to describe the performance of a new user-friendly comprehensive
      data analysis tool, the Integrated Pathogen Modeling Model (IPMP 2013), recently
      developed by the USDA Agricultural Research Service. This tool allows users,
      without detailed programming knowledge, to analyze experimental kinetic data and
      fit the data to known mathematical models commonly used in predictive
      microbiology. Data curves previously published in literature were used to test
      the models in IPMP 2013. The accuracies of the data analysis and models derived
      from IPMP 2013 were compared in parallel to commercial or open-source statistical
      packages, such as SAS(r) or R. Several models were analyzed and compared,
      including a three-parameter logistic model for growth curves without lag phases,
      reduced Huang and Baranyi models for growth curves without stationary phases,
      growth models for complete growth curves (Huang, Baranyi, and re-parameterized
      Gompertz models), survival models (linear, re-parameterized Gompertz, and Weibull
      models), and secondary models (Ratkowsky square-root, Huang square-root,
      Cardinal, and Arrhenius-type models). The comparative analysis suggests that the
      results from IPMP 2013 were equivalent to those obtained from SAS(r) or R. This
      work suggested that the IPMP 2013 could be used as a free alternative to SAS(r),
      R, or other more sophisticated statistical packages for model development in
      predictive microbiology. 

PMID- 24334096
TI  - Investigating the proteins released by yeasts in synthetic wine fermentations.
AB  - Proteins from various biological sources previously identified in wine play
      important roles in the functioning and survival of their producers and may
      exhibit oenological properties. Yeasts contribute significantly to the protein
      pool during and after alcoholic fermentation. While the extracellular proteins of
      Saccharomyces cerevisiae, the main wine yeast species, have been characterised,
      those of non-Saccharomyces yeasts remain restricted to a few enzymes. A more
      comprehensive insight into all proteins released during fermentation could
      improve our understanding of how yeasts survive and interact in mixed culture
      fermentations. This study aimed to characterise the exo-proteome of Saccharomyces
      and selected non-Saccharomyces yeasts in pure and mixed cultures in a wine-like
      medium. While S. cerevisiae completed the fermentation rapidly, Metschnikowia
      pulcherrima hardly fermented and Lachancea thermotolerans fermented slowly but
      steadily. In sequential fermentations, the kinetics resembled those of the non
      Saccharomyces yeasts for a period before switching to that of S. cerevisiae.
      Identification of the proteins present in wine at the end of fermentation using
      mass fingerprinting revealed the large diversity of proteins secreted and the
      influence of yeast interactions therein. The fermentation kinetics observed could
      partially be explained by the extent of the contribution of the different yeast
      to the protein content. 

PMID- 24334097
TI  - Quantitative assessment of the risk of microbial spoilage in foods. Prediction of
      non-stability at 55  degrees C caused by Geobacillus stearothermophilus in canned
      green beans.
AB  - Microbial spoilage of canned foods by thermophilic and highly heat-resistant
      spore-forming bacteria, such as Geobacillus stearothermophilus, is a persistent
      problem in the food industry. An incubation test at 55  degrees C for 7 days,
      then validation of biological stability, is used as an indicator of compliance
      with good manufacturing practices. We propose a microbial risk assessment model
      predicting the percentage of non-stability due to G. stearothermophilus in canned
      green beans manufactured by a French company. The model accounts for initial
      microbial contaminations of fresh unprocessed green beans with G.
      stearothermophilus, cross-contaminations in the processing chain, inactivation
      processes and probability of survival and growth. The sterilization process is
      modeled by an equivalent heating time depending on sterilization value F0 and on
      G. stearothermophilus resistance parameter z(T). Following the recommendations of
      international organizations, second order Monte-Carlo simulations are used,
      separately propagating uncertainty and variability on parameters. As a result of
      the model, the mean predicted non-stability rate is of 0.5%, with a 95%
      uncertainty interval of [0.1%; 1.2%], which is highly similar to data
      communicated by the French industry. A sensitivity analysis based on Sobol
      indices and some scenario tests underline the importance of cross-contamination
      at the blanching step, in addition to inactivation due to the sterilization
      process.

PMID- 24334098
TI  - A pulse sequence optimization method for assessment of nucleus size in q-space
      analysis of idealized cells.
AB  - To adjust pulse sequences that produce diffusion-weighted MRI signals for
      increased sensitivity to nucleus size, the impulse-propagator method in q-space
      is applied to a spherical geometry that would describe each member of a
      collection of cells and their nuclei, with several possible representations of
      the extracellular space. The method is extended to allow propagation between
      nucleus, cytoplasm, and extracellular space through semi-permeable membranes,
      using an approximate adjustment of intra-compartment propagators. Diffraction
      patterns are first calculated for the three compartments separately, for PGSE and
      OGSE pulse sequences, and verified by comparison with Monte Carlo simulations.
      The detailed patterns from the separate compartments determine the q value for
      maximum contrast in the total signal between large and small nuclei, an
      optimization that is not accurate in a Gaussian Phase Distribution (GPD)
      approximation. Then diffraction patterns are calculated for the case of linked
      compartments with semi-permeable membranes. The treatment of permeability
      adequately estimates pulse-sequence parameters for maximum contrast in calculated
      signal as nucleus size varies. 

PMID- 24334099
TI  - Parvilucifera rostrata sp. nov. (Perkinsozoa), a novel parasitoid that infects
      planktonic dinoflagellates.
AB  - The diversity and ecological roles of protists in marine plankton are still
      poorly known. In 2011, we made a substantial effort to isolate parasites into
      cultures during the course of blooms of the toxic microalga Alexandrium minutum
      (Dinophyceae) in two estuaries (the Penze and the Rance, Brittany coast, north
      west of France). In total, 99 parasitic strains were obtained. Screening of
      ribosomal internal transcribed spacer regions (including ITS1, 5.8S and ITS2)
      revealed the existence of two ribotypes. Small subunit and partial large subunit
      rRNA genes revealed that these two ribotypes belong to different species of the
      genus Parvilucifera. The first ribotype was tentatively affiliated to the species
      Parvilucifera infectans, whilst the second represents a new species,
      Parvilucifera rostrata sp. nov. The new species has several distinct
      morphological features in the general organization of its zoospore and in the
      shape and size of processes covering the sporangium. Both Parvilucifera species
      are generalist parasitoids with similar generation times, and this study thus
      raises the question of how two parasitoids exploiting similar ecological
      resources and infection strategies can coexist in the same ecosystem. Taxonomic
      relationships between Parvilucifera spp. and other closely related marine
      parasitoids, such as syndinians, are discussed. 

PMID- 24334100
TI  - Proteomic analysis of non-heading Chinese cabbage infected with Hyaloperonospora
      parasitica.
AB  - Downy mildew is a serious fungal disease in non-heading Chinese cabbage (Brassica
      campestris ssp. chinensis Makino) that is caused by Hyaloperonospora parasitica,
      which infects members of the Brassicaceae family. For breeding improvement,
      researchers must understand the defence mechanisms employed by non-heading
      Chinese cabbage to combat H. parasitica infection. Using 2-DE protein analysis,
      we compared the proteomes from leaves of non-heading Chinese cabbage seedlings
      that were infected with H. parasitica or that were only treated with water at
      different time points post-infection. By MS analysis, 91 protein spots with
      significant differences in abundance (>2-fold, p<0.05) were identified in mock-
      and H. parasitica-inoculated leaves. Next, a resistance strategy for incompatible
      interactions was proposed. This network consisted of several functional
      components, including enhanced ethylene biosynthesis and energy supply, balanced
      ROS production and scavenging, accelerated protein metabolism and
      photorespiratory, reduced photosynthesis, and induced photosystem repair. These
      findings increase our knowledge of incompatible interactions between plants and
      pathogens and also provide new insight regarding the function of plant molecular
      processes, which should assist in the discovery of new strategies for pathogen
      control. BIOLOGICAL SIGNIFICANCE: This study reported the proteomic analysis of
      the incompatible interactions between non-heading Chinese cabbage and downy
      mildew using 2-DE and MS. In total, 91 protein spots that were related to the
      resistance response were identified. These proteins were assigned to different
      functional categories, such as amino acid and carbohydrate metabolism,
      photosynthesis and photorespiration, protein metabolism, signal transduction,
      redox homeostasis, and ethylene biosynthesis. Meanwhile, several key proteins
      were determined to be associated with ethylene signalling, ROS scavenging and
      resistance-related proteins. Consistent with these results, the expression of
      ethylene biosynthesis genes and response genes, as well as the activity of
      antioxidant enzymes, increased after inoculation. These findings provide new
      insight for further understanding the molecular mechanisms of plant resistance.

PMID- 24334101
TI  - Melanoma attributable to sunbed use and tan seeking behaviours: an Italian
      survey.
AB  - Melanoma is the most deadly form of skin cancer and its incidence is increasing
      worldwide. In 2009, the International Agency for Research on Cancer classified
      the entire UV spectrum as carcinogenic. In many countries, including Italy, the
      use of tanning equipment by minors and individuals with high risk phenotypes has
      been banned. This study assessed tan-seeking behaviour in a Mediterranean
      population with a relatively high melanoma incidence, where a considerable time
      is spent tanning outdoors. Subjects spending the most time in the sun were
      typically young single men, who use significantly less sunscreen and sunglasses.
      The overall prevalence of sunbed use was 22% in youth (<=35 years old) and 18% of
      them used sunbeds throughout the year. Sunbed use in youth was greater for
      phenotypes at risk. In Italy, 3.8% of melanoma cases are attributable to sunbed
      use, more in women (4.2% vs 3.1%, for women and men respectively) and much more
      in the young (17%). Of 8013 new melanoma cases in 2008 in Italy, 293 were
      attributable to sunbed use, with a high proportion of these in women (168) and
      1045 were attributable to sun exposure. Among youth, 172 cases were attributable
      to sunbed use and 140 exclusively to sunbed use. This analysis reveals that a
      large number of cancers each year in Italy could be avoided by changing cultural
      attitudes to tanning. Sun avoidance and protection is generally inadequate in
      adults, especially young men. These results have important implications for the
      primary prevention of melanoma. 

PMID- 24334102
TI  - Caesappin A and B, two novel protosappanins from Caesalpinia sappan L.
AB  - Two novel protosappanins, named Caesappin A (1) and B (2), along with three known
      protosappanins were isolated from Caesalpinia sappan L. Caesappin A is a new type
      protosappanin with a seven-membered ring fusing an acetal-type section. Compound
      4 was isolated from the genus Caesalpinia for the first time. The structures were
      elucidated on the basis of spectral analysis and the absolute configuration was
      determined by the ECD experiment coupled with calculated ECD spectra. Their
      cytotoxic activities were evaluated using MTT assay. 

PMID- 24334103
TI  - Phlorotannins isolated from the edible brown alga Ecklonia stolonifera exert anti
      adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBPalpha and
      PPARgamma.
AB  - The dramatic increase in obesity-related diseases emphasizes the need to
      elucidate the cellular and molecular mechanisms underlying fat metabolism.
      Inhibition of adipocyte differentiation has been suggested to be an important
      strategy for preventing or treating obesity. In our previous study, we
      characterized an Ecklonia stolonifera extract and non-polar fractions thereof,
      including dichloromethane and ethyl acetate fractions. We showed that these
      fractions inhibited adipocyte differentiation and lipid formation/accumulation in
      3T3-L1 preadipocytes, as assessed by Oil Red O staining. As part of our ongoing
      search for anti-obesity agents derived from E. stolonifera, in this work, we
      characterized five known phlorotannins, including phloroglucinol, eckol, dieckol,
      dioxinodehydroeckol, and phlorofucofuroeckol A, all of which were isolated from
      the active ethyl acetate fraction of E. stolonifera. We determined the chemical
      structures of these phlorotannins through comparisons of published nuclear
      magnetic resonance (NMR) spectral data. Furthermore, we screened these
      phlorotannins for their abilities to inhibit adipogenesis over a range of
      concentrations (12.5-100 MUM). Of these five phlorotannins, phloroglucinol,
      eckol, and phlorofucofuroeckol A significantly concentration-dependently
      inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability. In
      addition, the five isolated phlorotannins also significantly reduced the
      expression levels of several adipocyte marker genes, including proliferator
      activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha
      (C/EBPalpha), although they did so to different extents. These results suggest
      that the molecular weight of a phlorotannin is an important factor affecting its
      ability to inhibit adipocyte differentiation and modulate the expression levels
      of adipocyte marker genes.

PMID- 24334104
TI  - Cowabenzophenones A and B, two new tetracyclo[7.3.3.3(3,11).0(3,7)]tetradecane
      2,12,14-trione derivatives, from ripe fruits of Garcinia cowa.
AB  - Two new tetracyclo[7.3.3.3(3,11).0(3,7)]tetradecane-2,12,14-trione derivatives,
      cowabenzophenones A (1) and B (2), were isolated from ripe fruits of Garcinia
      cowa Roxb. Their structures were determined by spectroscopic methods. The
      tetracyclo[7.3.3.3(3,11).0(3,7)]tetradecane-2,12,14-trione skeleton from the
      Garcinia genus is reported for the first time. 

PMID- 24334105
TI  - An integrative model of rational imitation in infancy.
AB  - It has been proposed that infants selectively imitate based on a rational
      evaluation of an observed action (Gergely, Bekkering, & Kiraly, 2002). This
      rational-imitation account has been rejected based on findings which suggested
      that infant imitation depends on: (a) the similarity between the infant's and the
      model's body posture; and (b) the presence of action effects (Paulus, Hunnius,
      Vissers, & Bekkering, 2011). Despite this controversy, we show that both accounts
      have received empirical support from different fields of research. We propose
      that both accounts operate on different levels, and we present an integrative
      model, which combines the two seemingly competing accounts. Motor resonance is
      perceived as a mechanism that enables infants to imitate, and a rational
      evaluation of the model's action is conceived as a mechanism that guides infants'
      imitative behavior. 

PMID- 24334106
TI  - Activation of Src family tyrosine kinases by ferric ions.
AB  - The Src-family tyrosine kinases (SFKs) are oncogenic enzymes that contribute to
      the initiation and progression of many types of cancer. In normal cells, SFKs are
      kept in an inactive state mainly by phosphorylation of a consensus regulatory
      tyrosine near the C-terminus (Tyr(530) in the SFK c-Src). As recent data indicate
      that tyrosine modification enhances binding of metal ions, the hypothesis that
      SFKs might be regulated by metal ions was investigated. The c-Src C-terminal
      peptide bound two Fe(3+) ions with affinities at pH4.0 of 33 and 252MUM, and
      phosphorylation increased the affinities at least 10-fold to 1.4 and 23MUM, as
      measured by absorbance spectroscopy. The corresponding phosphorylated peptide
      from the SFK Lyn bound two Fe(3+) ions with much higher affinities (1.2pM and
      160nM) than the Src C-terminal peptide. Furthermore, when Lyn or Hck kinases,
      which had been stabilised in the inactive state by phosphorylation of the C
      terminal regulatory tyrosine, were incubated with Fe(3+) ions, a significant
      enhancement of kinase activity was observed. In contrast Lyn or Hck kinases in
      the unphosphorylated active state were significantly inhibited by Fe(3+) ions.
      These results suggest that Fe(3+) ions can regulate SFK activity by binding to
      the phosphorylated C-terminal regulatory tyrosine. 

PMID- 24334107
TI  - "Piensa" twice: on the foreign language effect in decision making.
AB  - In this article, we assess to what extent decision making is affected by the
      language in which a given problem is presented (native vs. foreign). In
      particular, we aim to ask whether the impact of various heuristic biases in
      decision making is diminished when the problems are presented in a foreign
      language. To this end, we report four main studies in which more than 700
      participants were tested on different types of individual decision making
      problems. In the first study, we replicated Keysar et al.'s (2012) recent
      observation regarding the foreign language effect on framing effects related to
      loss aversion. In the second section, we assessed whether the foreign language
      effect is present in other types of framing problems that involve psychological
      accounting biases rather than gain/loss dichotomies. In the third section, we
      studied the foreign language effect in several key aspects of the theory of
      decision making under risk and uncertainty. In the fourth study, we assessed the
      presence of a foreign language effect in the cognitive reflection test, a test
      that includes logical problems that do not carry emotional connotations. The
      absence of such an effect in this test suggests that foreign language leads to a
      reduction of heuristic biases in decision making across a range of decision
      making situations and provide also some evidence about the boundaries of the
      phenomenon. We explore several potential factors that may underlie the foreign
      language effect in decision making. 

PMID- 24334108
TI  - Developmental investigation of fear-potentiated startle across puberty.
AB  - The goal of this study was to examine the association between affective
      development, puberty, and gender using the startle reflex as a marker of
      defensive mechanisms. Thirty-one male and thirty-five female adolescents aged ten
      to thirteen participated in a prospective study with up to five assessments.
      Longitudinal analyses revealed a significant effect of sex, with girls showing
      stronger fear-potentiation at all pubertal stages. Post hoc tests revealed that
      fear-potentiation increased in girls but not boys over the course of puberty.
      Furthermore, baseline startle decreased over the course of puberty. Because age
      was included as a covariate in all analyses, the puberty effect cannot be
      accounted for by age. To the best of our knowledge, this study provides the first
      evidence for a significant increase in fear-potentiated startle across the
      pubertal transition. Attribution of these changes to pubertal status rather than
      age has important implications for our understanding of the neurobiology of
      anxiety and affect regulation. 

PMID- 24334109
TI  - Distinct associations of insula and cingulate volume with the cognitive and
      affective dimensions of alexithymia.
AB  - Alexithymia ("no words for feelings") is a major risk factor for psychosomatic
      and psychiatric conditions characterized by affect dysregulation. The alexithymia
      personality construct comprises an affective dimension, the level of subjective
      emotional experience (emotionalizing and fantasizing), and a cognitive dimension,
      referring to the cognitive control of emotions (identifying, analyzing, and
      verbalizing feelings). These two dimensions may differentially put individuals at
      risk for psychopathology, but their specific neural bases have rarely been
      investigated. Therefore, the aim of the present study was to find out whether the
      two alexithymia dimensions are associated with discriminable neural correlates.
      By means of voxel-based morphometry (VBM), differences in gray matter volumes
      were compared between 20 (10 male) high-scorers and 20 (9 male) low-scorers on
      the Toronto Alexithymia Scale (TAS-20), reflecting the cognitive alexithymia
      dimension. In a subset of 32 subjects, the impact of the affective alexithymia
      dimension was tested in addition, as assessed with the affective subscale of the
      Bermond-Vorst Alexithymia Questionnaire (BVAQ). Analysis 1 (cognitive alexithymia
      dimension) revealed significantly larger gray matter volumes in the right
      posterior insula in high-scorers compared to low-scorers on the TAS-20. Analysis
      2 (affective alexithymia dimension) revealed that the affective alexithymia
      dimension, specifically the emotionalizing factor indicative of low emotional
      reactivity, was associated with larger gray matter volumes of the right cingulate
      cortex. These results suggest that the two alexithymia dimensions are associated
      with distinct structural correlates. 

PMID- 24334110
TI  - Automatic online control of motor adjustments in reaching and grasping.
AB  - Following the princeps investigations of Marc Jeannerod on action-perception,
      specifically, goal-directed movement, this review article addresses visual and
      non-visual processes involved in guiding the hand in reaching or grasping tasks.
      The contributions of different sources of correction of ongoing movements are
      considered; these include visual feedback of the hand, as well as the often
      neglected but important spatial updating and sharpening of goal localization
      following gaze-saccade orientation. The existence of an automatic online process
      guiding limb trajectory toward its goal is highlighted by a series of princeps
      experiments of goal-directed pointing movements. We then review psychophysical,
      electrophysiological, neuroimaging and clinical studies that have explored the
      properties of these automatic corrective mechanisms and their neural bases, and
      established their generality. Finally, the functional significance of automatic
      corrective mechanisms-referred to as motor flexibility-and their potential use in
      rehabilitation are discussed. 

PMID- 24334111
TI  - Comment on the reports of over-estimation of ASCVD risk using the 2013 AHA/ACC
      risk equation.

PMID- 24334112
TI  - Response to Comment on the reports of over-estimation of ASCVD risk using the
      2013 AHA/ACC risk equation.

PMID- 24334113
TI  - Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the
      influence of LCPUFA on neural development, aging, and neurodegeneration.
AB  - Many clinical and animal studies demonstrate the importance of long-chain
      polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration.
      This review will focus on involvement of LCPUFA from genesis to senescence. The
      LCPUFA docosahexaenoic acid and arachidonic acid are important components of
      neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and
      arachidonic acid also affect cardiovascular health and inflammation. In neural
      development, LCPUFA deficiency can lead to severe disorders like schizophrenia
      and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation
      demonstrated beneficial effects in neural development in humans and rodents
      resulting in improved cognition and sensorimotor integration. In normal aging,
      the effect of LCPUFA on prevention of cognitive impairment will be discussed.
      LCPUFA are important for neuronal membrane integrity and function, and also
      contribute in prevention of brain hypoperfusion. Cerebral perfusion can be
      compromised as result of obesity, cerebrovascular disease, hypertension, or
      diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most
      common neurodegenerative diseases like Alzheimer's disease and Parkinson's
      disease. These disorders are characterized by impaired cognition and connectivity
      and both clinical and animal supplementation studies have shown the potential of
      LCPUFA to decrease neurodegeneration and inflammation. This review shows that
      LCPUFA are essential throughout life. 

PMID- 24334114
TI  - Lysosome-associated protein 1 (LAMP-1) and lysosome-associated protein 2 (LAMP-2)
      in a larger family carrier of Fabry disease.
AB  - This study investigated the potential relationship between the expression levels
      of lysosome-associated membrane proteins (LAMP) 1 and 2 and responses to enzyme
      replacement therapy (ERT) in the members of a single family with Fabry disease
      (FD). LAMP levels were assessed by flow cytometry in leukocytes from 17 FD
      patients who received an eight-month course of ERT course and 101 healthy
      individuals. We found that phagocytic cells from the FD patients had higher
      expression levels of both LAMP-1 and LAMP-2, relative to the levels in phagocytes
      from the healthy controls (p=0.001). Furthermore, the LAMP-1 and LAMP-2 levels in
      phagocytes from the FD carriers continuously decreased with ERT administration to
      reach levels similar to those in healthy controls. We suggest that LAMP-1 and
      LAMP-2 could be used as additional markers with which to assess ERT effectiveness
      in FD. 

PMID- 24334115
TI  - Combined genetic mutations have remarkable effect on deep venous thrombosis
      and/or pulmonary embolism occurence.
AB  - PURPOSE: Although deep vein thrombosis and thromboembolic diseases differ among
      various races, they are still important in our day. The difficulties in treatment
      and following-up of these diseases are caused by secret genetic mutations rather
      than predisposing factors. METHODS: Between January 2011 and May 2013, patients
      who were traced for deep vein thrombosis and/or pulmonary embolism were evaluated
      retrospectively. 84 patients (53.6% males and 46.4% females) were included in the
      study. Their family histories, predisposing factors and treatments were
      researched. Factor V Leiden (G 1691A), Factor II G20210A, Plasminogen Activator
      Inhibitor-Type 1 (4G/5G), and Methylene Tetrahydrofolate Reductase (C677T,
      A1298C) mutations were investigated from peripheral venous blood. RESULTS: Among
      the genetic mutations we searched, the incidence of single mutation rate was
      observed at 11.9%, double mutation collocation at 44%, triple mutation
      collocation at 29.8%, quadruple mutation collocation at 13.1%, and finally,
      quintuplet mutation collocation at 1.2%. Our approximate mutation number was
      found as 2.47 +/- 0.91. CONCLUSION: We observed that multiple mutations were high
      in number compared to single genetic mutations. The patients who have multiple
      mutations should be more in the front line considering their diagnosis, treatment
      and following up, and also in terms of decreasing mortality, morbidity and
      recurrence.

PMID- 24334116
TI  - Reduced glucosylceramide in the mouse model of Fabry disease: correction by
      successful enzyme replacement therapy.
AB  - Fabry disease is an X-linked lysosomal storage disease (LSD) caused by deficient
      activity of alpha-Galactosidase A (alpha-Gal A). As a result, glycosphingolipids,
      mainly globotriaosylceramide (Gb3), progressively accumulate in body fluids and
      tissues. Studies aiming at the identification of secondary lipid alterations in
      Fabry disease may be potentially useful for the monitorization of the response to
      enzyme replacement therapy (ERT) and development of future therapies. The focus
      of this study was to evaluate if alpha-Gal A deficiency has an effect on two key
      groups of molecules of sphingolipids metabolism: glucosylceramides (GlucCers) and
      ceramides (Cers). Studies performed in a mouse model of Fabry disease showed
      reduced level of GlucCer and normal level of Cer in plasma, liver, spleen, kidney
      and heart. Moreover, analysis of GlucCer isoforms in Fabry knockout mice showed
      that GlucCer isoforms are unequally reduced in different tissues of these
      animals. ERT had a specific effect on the liver's GlucCer levels of Fabry
      knockout mice, increasing hepatic GlucCer to the levels observed in wild type
      mice. In contrast to Fabry knockout mice, plasma of Fabry patients had normal
      GlucCer and Cer but an increased GlucCer/Cer ratio. This alteration showed a
      positive correlation with plasma globotriaosylsphingosine (lyso-Gb3)
      concentration. In conclusion, this work reveals novel secondary lipid imbalances
      caused by alpha-Gal A deficiency. 

PMID- 24334117
TI  - The myostatin gene of Mytilus chilensis evidences a high level of polymorphism
      and ubiquitous transcript expression.
AB  - Myostatin (MSTN) is a protein of the Transforming Growth Factor-beta (TGF-beta)
      superfamily and plays a crucial role in muscular development for higher
      vertebrates. However, its biological function in marine invertebrates remains
      undiscovered. This study characterizes the full-length sequence of the Mytilus
      chilensis myostatin gene (Mc-MSTN). Furthermore, tissue transcription patterns
      and putative single nucleotide polymorphisms (SNPs) were also identified. The Mc
      MSTN cDNA sequence showed 3528 base pairs (bp), consisting of 161 bp of 5' UTR,
      2,110 bp of 3' UTR, and an open reading frame of 1,257 bp encoding for 418 amino
      acids and with an RXXR proteolytic site and nine cysteine-conserved residues.
      Gene transcription analysis revealed that the Mc-MSTN has ubiquitous expression
      among several tissues, with higher expression in the gonads and mantle than in
      the digestive gland, gills, and hemolymph. Furthermore, high levels of
      polymorphisms were detected (28 SNPs in 3'-UTR and 9 SNPs in the coding region).
      Two SNPs were non-synonymous and involved amino acid changes between Glu/Asp and
      Thr/Ile. Until now, the MSTN gene has been mainly related to muscle growth in
      marine bivalves. However, the present study suggests a putative biological
      function not entirely associated to muscle tissue and contributes molecular
      evidence to the current debate about the function of the MSTN gene in marine
      invertebrates.

PMID- 24334119
TI  - Involvement of the single Cul4 gene of Chinese mitten crab Eriocheir sinensis in
      spermatogenesis.
AB  - The Cullin-RING finger ligases (CRLs) are involved in the ubiquitin-mediated
      degradation of cell cycle regulators and play an important role in gametogenesis.
      Cullin 4 (CUL4) is a conserved core component of a new class of ubiquitin E3
      ligase, and participates in the proteolysis of several regulatory proteins
      through the ubiquitin-proteasome pathway. The mammals encode two paralogs of
      CUL4, CUL4A and CUL4B, and the two Cul4 genes are functionally redundant.
      However, Drosophila or other metazoans only contain one Cul4 gene. Here we cloned
      the Cul4 gene and confirmed that there is only one protein of CUL4 in Eriocheir
      sinensis, a full length Cul4 comprised of 2777 nucleotides, an open-reading frame
      of 2373bp encoding 790 amino acid residues. The expression level of Cul4 mRNAs,
      as demonstrated by quantitative real-time PCR, varied significantly during testis
      development, with the greatest transcript levels found at an early stage.
      Localization analysis using antibodies against CUL4A/4B in the reproductive
      system showed that EsCUL4 mainly distribute in spermatogonia and primary
      spermatocytes, and gradually reduced during the development and maturation of
      sperm. The results indicated that a single CUL4 protein may play a role in
      spermatogenesis in E. sinensis. 

PMID- 24334118
TI  - Expression of the 78 kD glucose-regulated protein is induced by endoplasmic
      reticulum stress in the development of hepatopulmonary syndrome.
AB  - OBJECTIVE: This study is to explore the role of 78 kD glucose-regulated protein
      (GRP78) in the development of hepatopulmonary syndrome (HPS) in rats. METHODS:
      The rat model of liver cirrhosis and HPS were induced with multiple pathogenic
      factors. Hematoxylin and eosin (H & E) staining was performed to detect the
      pathological changes of the lung and liver tissues. The levels of alanine
      transferase (ALT), endotoxin, and tumor necrosis factor-alpha (TNF-alpha) in
      plasma and TNF-alpha and malondialdehyde (MDA) in lung tissues were detected. RT
      PCR and Western blotting were conducted to detect the mRNA and protein expression
      levels of GRP78 in lungs. RESULTS: The plasma endotoxin level was gradually
      increased as HPS developed, and the mRNA and protein expression levels of GRP78
      in lungs were also increased as the disease progressed. The levels of ALT and TNF
      alpha in plasma and the contents of TNF-alpha and MDA in lung tissues were
      gradually increased along with the disease progression, with a strong positive
      correlation. Compared with controls, the plasma TNF-alpha level and the mRNA and
      protein expression levels of GRP78 in lung tissues were significantly higher in
      rats with HPS. The levels of endotoxin and ALT in plasma and the level of MDA in
      lungs were significantly higher in rats with HPS than controls. CONCLUSIONS: The
      increased GRP78 expression is indicative of endoplasmic reticulum stress response
      during HPS, which may play an important role in the disease pathogenesis.

PMID- 24334120
TI  - Down-regulation of ribosomal protein S15A mRNA with a short hairpin RNA inhibits
      human hepatic cancer cell growth in vitro.
AB  - Ribosomal protein s15a (RPS15A) is a highly conserved protein that promotes
      mRNA/ribosome interactions early in translation. Recent evidence showed that
      RPS15A could stimulate growth in yeast, plant and human lung carcinoma. Here we
      report that RPS15A knockdown could inhibit hepatic cancer cell growth in vitro.
      When transduced with shRPS15A-containing lentivirus, we observed inhibited cell
      proliferation and impaired colony formation in both HepG2 and Bel7404 cells.
      Furthermore, cell cycle analysis showed that HepG2 cells were arrested at the
      G0/G1 phase when transduced with Lv-shRPS15A. In conclusion, our findings provide
      for the first time the biological effects of RPS15A in hepatic cancer cell
      growth. RPS15A may play a prominent role in heptocarcinogenesis and serve as a
      potential therapeutic target in hepatocellular carcinoma. 

PMID- 24334121
TI  - Trehalose metabolism in the blue crab Callinectes sapidus: isolation of multiple
      structural cDNA isoforms of trehalose-6-phosphate synthase and their expression
      in muscles.
AB  - Adult blue crab Callinectes sapidus exhibit behavioral and ecological
      dimorphisms: females migrating from the low salinity water to the high salinity
      area vs. males remaining in the same areas. The flesh basal muscle of the
      swimming paddle shows a dimorphic color pattern in that levator (Lev) and
      depressor (Dep) of females tend to be much darker than those of males, while both
      genders have the same light colored remoter (Rem) and promoter (Pro). The full
      length cDNA sequence of four structural isoforms of trehalose-6-phosphate
      synthase (TPS) is isolated from chela muscles of an adult female, C. sapidus. Two
      isoforms of the C. sapidus TPS encode functional domains of TPS and trehalose-6
      phosphorylase (TPP) in tandem as a fused gene product of Escherichia coli Ost A
      and Ost B. The other two isoforms contain only a single TPS domain. In both males
      and females, the darker (Lev+Dep) muscles exhibit greater amounts of trehalose,
      TPS and trehalase activities than the light colored (Rem+Pro). The fact that
      adult females show higher levels of trehalase activity in the basal muscles and
      of glucose in Lev+Dep than those of adult males suggests that there may be a
      metabolic dimorphism. Moreover, the involvement of trehalose in energy metabolism
      that was examined under the condition of strenuous swimming activity mimicked in
      adult females demonstrates the intrinsic trehalose metabolism in Lev+Dep, which
      subsequently results in hemolymphatic hyperglycemia and hyperlactemia. Our data
      support that trehalose serves as an additional carbohydrate source of
      hemolymphatic hyperglycemia in this species. Behavioral and ecological
      dimorphisms of C. sapidus adults may be supported by a functional dimorphism in
      energy metabolism. 

PMID- 24334122
TI  - A patient with partial trisomy 21 and 7q deletion expresses mild Down syndrome
      phenotype.
AB  - BACKGROUND: Down syndrome (DS) is the most common aneuploidy in live-born
      individuals and it is well recognized with various phenotypic expressions.
      Although an extra chromosome 21 is the genetic cause for DS, specific phenotypic
      features may result from the duplication of smaller regions of the chromosome and
      more studies need to define genotypic and phenotypic correlations. CASE REPORT:
      We report on a 26 year old male with partial trisomy 21 presenting mild clinical
      symptoms relative to DS including borderline intellectual disability. In
      particular, the face and the presence of hypotonia and keratoconus were
      suggestive for the DS although the condition remained unnoticed until his adult
      age array comparative genomic hybridization (aCGH) revealed a 10.1 Mb duplication
      in 21q22.13q22.3 and a small deletion of 2.2 Mb on chromosomal band 7q36 arising
      from a paternal translocation t(7;21). The 21q duplication encompasses the gene
      DYRK1. CONCLUSION: Our data support the evidence of specific regions on distal
      21q whose duplication results in phenotypes recalling the typical DS face.
      Although the duplication region contains DYRK1, which has previously been
      implicated in the causation of DS, our patient has a borderline IQ confirming
      that their duplication is not sufficient to cause the full DS phenotype.

PMID- 24334123
TI  - Characterization of a glutamine synthetase gene DvGS2 from Dunaliella viridis and
      biochemical identification of DvGS2-transgenic Arabidopsis thaliana.
AB  - The salt-tolerant green alga Dunaliella has remarkable capability to survive in
      some extreme environments such as nitrogen starvation, which makes Dunaliella be
      a proper model for mining novel genes on nitrogen uptake or assimilation. In this
      study, a glutamine synthetase (GS) gene DvGS2 with amino acid identity of 72% to
      other homologous GS proteins, was isolated and characterized from Dunaliella
      viridis. Phylogenetic comparison with other GSs revealed that DvGS2 occupied an
      independent phylogenetic position. Expressional analysis in D. viridis cells
      under nitrogen starvation confirmed that DvGS2 increased its mRNA level in 12h.
      Subcellular localization study and functional analysis in a GS-deficient
      Escherichia coli mutant proved that DvGS2 was a chloroplastic and functional GS
      enzyme. In order to investigate the potential application of DvGS2 in higher
      plants, the transgenic studies of DvGS2 in Arabidopsis thaliana were carried out.
      Results showed that the transgenic lines expressed the DvGS2 gene and
      demonstrated obviously enhanced root length (29%), fresh weight (40%-48% at two
      concentrations of nitrate supplies), stem length (21%), leaf size (39%) and
      silique number (44%) in contrast with the wild-type Arabidopsis. Furthermore, the
      transgenic lines had higher total nitrogen content (35%-43%), total GS activity
      (39%-45%) and soluble protein concentration (23%-24%) than the wild type. These
      results indicated that the overexpression of DvGS2 in A. thaliana resulted in
      higher biomass and the improvement of the host's nitrogen use efficiency. 

PMID- 24334124
TI  - Two ancestral APETALA3 homologs from the basal angiosperm Magnolia wufengensis
      (Magnoliaceae) can affect flower development of Arabidopsis.
AB  - APETALA3 (AP3) homologs are involved in specifying petal and stamen identities in
      core eudicot model organisms. In order to investigate the functional conservation
      of AP3 homologs between core eudicots and basal angiosperm, we isolated and
      identified two AP3 homologs from Magnolia wufengensis, a woody basal angiosperm
      belonging to the family Magnoliaceae. Sequence and phylogenetic analyses revealed
      that both genes are clade members of the paleoAP3 lineage. Moreover, a highly
      conserved motif of paleoAP3 is found in the C-terminal regions of MAwuAP3_1/2
      proteins, but the PI-derived motif, usually present in AP3/DEF-like lineage
      members, is missing. Semi-quantitative and real time PCR analyses showed that the
      expression of MAwuAP3_1/2 was restricted to tepals and stamens. However, the
      MAwuAP3_1 expression was maintained at a high level during the rapid increased in
      size of tepals and stamens, while MAwuAP3_2 mRNA was only detected at the early
      stage of tepal and stamen development. Furthermore, the expression of MAwuAP3_1/2
      in transgenic Arabidopsis causes phenotypic changes which partly resemble those
      caused by ectopic expressions of the endogenous AP3 gene. Moreover, the
      35S::MAwuAP3_1/2 transgenic Arabidopsis can be used partially to rescue the loss
      of-function ap3 mutant (ap3-3) of Arabidopsis. These findings call for a more
      comprehensive understanding of the B-functional evolution from basal angiosperm
      to core eudicot clades. 

PMID- 24334125
TI  - Associations of variants in MTHFR and MTRR genes with male infertility in the
      Jordanian population.
AB  - Folate pathway is expected to play an important role in spermatogenesis since it
      is involved in DNA synthesis, repair and methylation. The purpose of this study
      was to examine the association between male infertility and the MTHFR (C677T and
      A1298C) and MTRR (A66G) polymorphisms. A group of 300 males was recruited in this
      study from different Jordanian infertility clinics. Of these, 150 cases of
      infertile men that included oligozoospermia cases (n=45), severe oligozoospermia
      (n=71) and azoospermia (n=34) were studied. The other 150 males were age matched
      fertile controls. Genotyping of MTHFR and MTRR polymorphisms was performed using
      PCR-RFLP technique. The results showed an association between MTHFR 677TT
      genotype and male infertility (P<0.05). However, the distribution of MTHFR A1298C
      and MTRR A66G genotypes were not different between the fertile and infertile
      groups (P>0.05). In addition, none of the examined polymorphisms was related to
      any of the semen parameters in the infertile group. In conclusion, this study
      showed that MTHFR C677T polymorphism is associated with male infertility in
      Jordanians. 

PMID- 24334126
TI  - Need for revising data in the recent meta-analysis of ADAM33 polymorphisms and
      asthma risk.

PMID- 24334127
TI  - Critical issues for the proper diagnosis of Metachromatic Leukodystrophy.
AB  - Metachromatic Leukodystrophy is a lysosomal storage disorder caused by
      Arylsulfatase A deficiency. Diagnosis is usually performed by measurement of
      enzymatic activity and/or characterization of the gene mutations. Here we
      describe a family case in which the determination of enzyme activity alone did
      not allow diagnosis of the pre-symptomatic sibling of the index case. Only
      combination of gene sequencing with thorough biochemical analysis allowed the
      correct diagnosis of the sibling, who was promptly directed to treatment. 

PMID- 24334128
TI  - Polysaccharide of Boschniakia rossica induces apoptosis on laryngeal carcinoma
      Hep2 cells.
AB  - The aim of this study was to explore the anti-tumor potential of a polysaccharide
      isolated from Boschniakia rossica (BRP) in Hep2 human larynx squamous carcinoma
      cells. High performance size-exclusion chromatography analysis showed that BRP
      was a homogeneous polysaccharide and had a molecular weight of 22 kDa. Total
      carbohydrate content in BRP was determined to be 96.9%, without the presence of
      protein and nucleic acid. BRP suppressed the proliferation of Hep2 cells in a
      time- and dose-dependent manner. Cell cycle analysis revealed that exposure to
      BRP (200 MUg/ml) caused a G0/G1 cell cycle arrest in Hep2 cells. Moreover,
      treatment with BRP at 100-400 MUg/ml for 24h induced a significant apoptosis Hep2
      cells compared to untreated control cells, as determined by flow cytometry with
      annexin-V/propidium iodide double staining. Additionally, BRP treatment promoted
      the cleavage of pro-caspase-3, pro-caspase-8, and pro-caspase-9, coupled with
      increased expression of death receptor DR5 and Bax and reduced expression of Bcl
      2. Taken together, our data demonstrate that BRP shows potent anti-tumor activity
      in human larynx squamous carcinoma, largely through induction of G0/G1 cell cycle
      arrest and apoptosis. Activation of both mitochondria-mediated and death receptor
      mediated apoptosis pathways is involved in the cytotoxicity of BRP.

PMID- 24334129
TI  - The variant hERG/R148W associated with LQTS is a mutation that reduces current
      density on co-expression with the WT.
AB  - BACKGROUND: A variant of the ether-a-go-go related channel (hERG), p.Arg148Trp
      (R148W) was found at heterozygous state in two infants who died from sudden
      infant death syndrome (SIDS), one with documented prolonged QTc and Torsade de
      Pointes (TdP), and in an adult woman with QTc >500 ms, atrioventricular block and
      TdP. This variant was previously reported in cases of severe ventricular
      arrhythmia but very rarely in control subjects. Its classification as mutation or
      polymorphism awaited electrophysiological characterization. METHODS: The
      properties of this N-terminal, proximal domain, hERG variant were explored in
      Xenopus oocytes injected with the same amount of RNA encoding for either hERG/WT
      or hERG/R148W or their equimolar mixture. The human ventricular cell (TNNP) model
      was used to test the effects of changes in hERG current. RESULTS: R148W alone
      produced a current similar to the WT (369 +/- 76 nA (mean +/- SEM), n=13 versus
      342 +/- 55 nA in WT, n=13), while the co-expression of 1/2 WT+1/2 R148W lowered
      the current by 29% versus WT (243 +/- 35 nA, n=13, p<0.05). The voltage
      dependencies of steady-state activation and inactivation were not changed in the
      variant alone or in co-expression with the WT. The time constants of fast
      recovery from inactivation and of fast and slow deactivation analyzed between 
      120 and +20 mV were not changed. The voltage-dependent distribution of the
      current amplitudes among fast-, slow- and non-deactivating fractions was
      unaltered. A 6.6% increase in APD90 from 323.5 ms to 345 ms was observed using
      the human cardiac ventricular myocyte model. CONCLUSIONS: Such a decrease in hERG
      current as evidenced here when co-expressing the hERG/R148W variant with the WT
      may have predisposed to the observed long QT syndrome and associated TdP.
      Therefore, the heterozygous carriers of hERG/R148W may be at risk of cardiac
      sudden death.

PMID- 24334130
TI  - Inhibition of PKR protects against tunicamycin-induced apoptosis in neuroblastoma
      cells.
AB  - Endoplasmic reticulum (ER) dysfunction is thought to play a significant role in
      several neurological disorders, including Alzheimer's disease, Parkinson's
      disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis,
      cerebral ischemia, and the prion diseases. ER dysfunction can be mimicked by
      cellular stress signals such as disruption of calcium homeostasis, inhibition of
      protein glycosylation, and reduction of disulfide bonds, which results in
      accumulation of misfolded proteins in the ER and leads to cell death by
      apoptosis. Tunicamycin, which is an inhibitor of protein glycosylation, induces
      ER stress and apoptosis. In this study, we examined the involvement of double
      stranded (ds) RNA-activated protein kinase PKR in tunicamycin-induced apoptosis.
      We used overexpression of the trans-dominant negative, catalytically inactive
      mutant K296R to inhibit PKR activity in neuroblastoma cells. We demonstrate that
      inhibition of PKR activation in response to tunicamycin protects neuronal cells
      from undergoing apoptosis. Furthermore, K296R overexpressing cells show defective
      PKR activation, delayed eIF2alpha phosphorylation, dramatically delayed ATF4
      expression. In addition, both caspase-3 activation and C/EBP homologous protein
      (CHOP, also known as GADD153) induction, which are markers of apoptotic cells,
      are absent from K296R overexpression cells in response to tunicamycin. These
      results establish that PKR activation plays a major regulatory role in induction
      of apoptosis in response to ER stress and indicates the potential of PKR as
      possible target for neuroprotective therapeutics. 

PMID- 24334131
TI  - [Editor's commentary. Advances in endocrinology].

PMID- 24334132
TI  - [Vitamin D and neuropathy].
AB  - Diabetes is a widespread disease and, therefore, studies dealing with diabetes
      and its complications are very important for public health. Numerous reports link
      vitamin D deficiency to the increased risk of diabetes mellitus and complications
      such as neuropathy. However, there are limited and conflicting data available on
      vitamin D deficiency in patients with diabetic peripheral neuropathy. Studies in
      type 2 diabetics confirmed the relationship between vitamin D deficiency and
      incidence of neuropathy. Recent reports suggest a relationship between the
      incidence of plantar ulcers and vitamin D deficiency.

PMID- 24334133
TI  - [The impact of thyroid function in women of reproductive age: infertility,
      pregnancy and the postpartum period].
AB  - This article reviews the management and diagnosis of thyroid dysfunction during
      pregnancy and postpartum, which was published by any of the endocrine societies
      in 2012. The author presents human data based on these clinical practice
      guidelines, however, there are also many unresolved questions. Especially, there
      are inconsistencies about screening using plasma TSH measurement. In pregnancy
      the main causes of hyperthyroidism are Graves's disease and gestational transient
      thyrotoxicosis. Generally, gestational transient thyrotoxicosis does not require
      medication, whereas Graves's disease needs antithyroid drug therapy. Postpartum
      thyroiditis occurs more frequently in antithyroid peroxidase-positive women, who
      should be screened using serum thyrotropin measurements at 6 to 12 gestation
      weeks and at 3 and 6 months postpartum. Because overt maternal hypothyroidism,
      due to autoimmune pathophysioloical mechanisms, negatively affects the fetus,
      timely recognition and treatment are important. The subclinical form of maternal
      hypothyroidism should also be treated. A link between thyroid dysfunction and
      infertility has been warranted.

PMID- 24334134
TI  - [Clinical value of two methods to measure parathyroid hormone in chronic renal
      insufficiency, considering vitamin D metabolism].
AB  - INTRODUCTION: Parathyroid hormone levels provide important information in chronic
      renal failure. AIM: To compare parathyroid hormone levels measured by two assays
      in correlation with vitamin D supply. METHOD: Parathyroid hormone and 25-hydroxi
      vitamin-D were determined in 104 patients (31 patients with chronic renal failure
      without renal replacement therapy, 36 patients treated with peritoneal dialysis
      and 37 patients treated with hemodialysis). RESULTS: Good correlation was found
      between results of the two parathyroid hormone methods, but the intact
      parathyroid hormone levels were higher than the biointact values. 87% and 13% of
      the patients had vitamin-D deficiency and insufficiency, respectively. The
      frequency of serious vitamin-D deficiency was higher in the peritoneal dialysis
      than in the hemodialysis group. Intact parathyroid hormone levels were different
      in dialysed patients having vitamin-D-deficiency and insufficiency, and the
      difference was higher for the biointact than intact values. Negative correlation
      was detected between biointact parathyroid hormone and 25-hydroxivitamin-D in the
      hemodialysis group. CONCLUSIONS: Biointact parathyroid hormone levels better
      reflect the vitamin D supply and bone metabolism than intact levels, especially
      in hemodialysed patients.

PMID- 24334135
TI  - [Various neuroendocrine tumors in a family with multiple endocrine neoplasia type
      1].
AB  - When multiple endocrine tumors are detected more tests are required to diagnose
      endocrine tumor syndromes. The authors report the case history of a patient with
      clinical manifestation of multiplex endocrine neoplasia type 1 (parathyroid
      adenoma, pancreatic neuroendocrine tumor, pituitary tumor, adrenal gland tumors
      and thymic neuroendocrine carcinoma). Genetic screening proved a novel stop codon
      mutation of the MEN1 gene in the patient and in two other members of the family.
      The son of the index patient showed clinical symptoms of pancreatic
      neuroendocrine tumor (insulinoma) and parathyroid adenoma. One of the two
      daughters was also positive for the same mutation, however, she had no clinical
      symptoms. The authors review current knowledge on the genetic background of
      multiple endocrine syndrome type 1, the role of menin and the usefulness of gene
      mutation screening.

PMID- 24334136
TI  - [The "blue man"].
AB  - The authors present the case of a 63-year-old man who was evaluated for symptoms
      of lung fibrosis, blue face and epithelopathy affecting both eyes. All these
      symptoms could be attributed to the adverse effects of amiodarone. Thyroid
      disorders, which are the most common side-effects of amiodarone treatment were
      absent. The authors want to draw attention to the potential side effects of
      amiodarone.

PMID- 24334138
TI  - Retinoic acid inhibits pancreatic cancer cell migration and EMT through the
      downregulation of IL-6 in cancer associated fibroblast cells.
AB  - Retinoic acid (RA) is a small molecular derivative of vitamin A that is stored in
      quiescent stellate cells in pancreas stroma. Cancer associated fibroblasts (CAFs)
      are activated fibroblast cells in pancreatic ductal adenocarcinoma tumor
      microenvironment. We treated CAFs with RA and found that these cells became
      static due to the low expression of alpha-SMA, FAP, and IL-6 and decreased
      production of extracellular matrix (ECM). Furthermore, we verified that the low
      secretion of IL-6 from CAFs was related to RA-induced inhibition of migration and
      epithelial-mesenchymal transition (EMT) of tumor cells. However, RA could not
      inhibit the migration and EMT of tumor cells directly. Therefore, our study
      showed that one of the therapeutic effects of RA on tumor cells is through its
      modulation of CAFs in tumor microenvironment. The tumor microenvironment plays an
      important role in promoting tumor migration and might be a promising target of
      biological treatment. 

PMID- 24334140
TI  - Far-infrared radiation inhibits proliferation, migration, and angiogenesis of
      human umbilical vein endothelial cells by suppressing secretory clusterin levels.
AB  - Far-infrared (FIR) radiation is known to lessen the risk of angiogenesis-related
      diseases including cancer. Because deficiency of secretory clusterin (sCLU) has
      been reported to inhibit angiogenesis of endothelial cells (EC), we investigated
      using human umbilical vein EC (HUVEC) whether sCLU mediates the inhibitory
      effects of FIR radiation. Although FIR radiation ranging 3-25MUm wavelength at
      room temperature for 60min did not alter EC viability, further incubation in the
      culture incubator (at 37 degrees C under 5% CO2) after radiation significantly
      inhibited EC proliferation, in vitro migration, and tube formation in a time
      dependent manner. Under these conditions, we found decreased sCLU mRNA and
      protein expression in HUVEC and decreased sCLU protein secreted in culture
      medium. Expectedly, the replacement of control culture medium with the FIR
      irradiated conditioned medium significantly decreased wound closure and tube
      formation of HUVEC, and vice versa. Furthermore, neutralization of sCLU with anti
      sCLU antibody also mimicked all observed inhibitory effects of FIR radiation.
      Moreover, treatment with recombinant human sCLU protein completely reversed the
      inhibitory effects of FIR radiation on EC migration and angiogenesis. Lastly,
      vascular endothelial growth factor also increased sCLU secretion in the culture
      medium, and wound closure and tube formation of HUVEC, which were significantly
      reduced by FIR radiation. Our results demonstrate a novel mechanism by which FIR
      radiation inhibits the proliferation, migration, and angiogenesis of HUVEC, via
      decreasing sCLU. 

PMID- 24334139
TI  - H460 non-small cell lung cancer stem-like holoclones yield tumors with increased
      vascularity.
AB  - Cancer stem-like cells were isolated from several human tumor cell lines by
      limiting dilution assays and holoclone morphology, followed by assessment of self
      renewal capacity, tumor growth, vascularity, and blood perfusion. H460 holoclone
      derived tumors grew slower than parental H460 tumors, but displayed significantly
      increased microvessel density and tumor blood perfusion. Microarray analysis
      identified 177 differentially regulated genes in the holoclone-derived tumors, of
      which 47 were associated with angiogenesis. The dysregulated genes include
      several small leucine-rich proteoglycans that may modulate angiogenesis and serve
      as novel therapeutic targets for inhibiting cancer stem cell-driven angiogenesis.

PMID- 24334141
TI  - mTOR-dependent transcriptional repression of Pdcd4 tumor suppressor in lung
      cancer cells.
AB  - Programmed cell death 4 (Pdcd4) tumor suppressor is frequently lost in tumors of
      various origins including lung cancer, and its loss contributes to tumor
      progression. However molecular mechanisms underlying Pdcd4 suppression in lung
      cancer cells remain largely unexplored. Here we investigated molecular mechanisms
      of Pdcd4 suppression in lung cancer cells. Besides enhanced mTOR-dependent
      proteasomal degradation of Pdcd4 protein, we found that Pdcd4 transcription is
      negatively regulated by mTOR signaling, and localized cis-acting element in Pdcd4
      promoter responsible for this effect. In conclusion, we described a novel
      molecular mechanism of Pdcd4 suppression in cancer cells consisting from mTOR
      signaling-dependent transcriptional repression of Pdcd4. 

PMID- 24334143
TI  - Injectable alginate hydrogels for cell delivery in tissue engineering.
AB  - Alginate hydrogels are extremely versatile and adaptable biomaterials, with great
      potential for use in biomedical applications. Their extracellular matrix-like
      features have been key factors for their choice as vehicles for cell delivery
      strategies aimed at tissue regeneration. A variety of strategies to decorate them
      with biofunctional moieties and to modulate their biophysical properties have
      been developed recently, which further allow their tailoring to the desired
      application. Additionally, their potential use as injectable materials offers
      several advantages over preformed scaffold-based approaches, namely: easy
      incorporation of therapeutic agents, such as cells, under mild conditions;
      minimally invasive local delivery; and high contourability, which is essential
      for filling in irregular defects. Alginate hydrogels have already been explored
      as cell delivery systems to enhance regeneration in different tissues and organs.
      Here, the in vitro and in vivo potential of injectable alginate hydrogels to
      deliver cells in a targeted fashion is reviewed. In each example, the selected
      crosslinking approach, the cell type, the target tissue and the main findings of
      the study are highlighted. 

PMID- 24334144
TI  - Biomaterials and design in occlusion devices for cardiac defects: a review.
AB  - This review examines the biomaterials used in occlusion devices for cardiac
      defects, and how the choice of these materials is dictated by design.
      Specifically, the devices used in three major applications, the atrial septal
      defect, the ventricular septal defect and the patent ductus arteriosus, are
      examined critically. A number of different devices are available, with varied
      performance in deployment and sealing. There is no device in any of the three
      categories that satisfies fully the range of requirements, and all have
      associated complications. The type and rate of complications are different among
      different devices. The short-term (immediate) complications are addressed by
      immediate retrieval. For longer-term complications, most of which can be fatal,
      currently only surgical retrieval and replacement are possible. Most of these
      longer-term complications can be alleviated by the use of fully degradable
      devices, which will eliminate concerns regarding the use of metals inside the
      heart, and if fully endothelialized, also minimize migration concerns. On the
      other hand, the lower moduli of currently available biodegradable materials need
      to be augmented. Improvements in the stiffness required for deployment can be
      accomplished with the use of fillers, nano- or micro-sized, and an example of
      this are radiopaque fillers. 

PMID- 24334142
TI  - Three-dimensional printed trileaflet valve conduits using biological hydrogels
      and human valve interstitial cells.
AB  - Tissue engineering has great potential to provide a functional de novo living
      valve replacement, capable of integration with host tissue and growth. Among
      various valve conduit fabrication techniques, three-dimensional (3-D) bioprinting
      enables deposition of cells and hydrogels into 3-D constructs with anatomical
      geometry and heterogeneous mechanical properties. Successful translation of this
      approach, however, is constrained by the dearth of printable and biocompatible
      hydrogel materials. Furthermore, it is not known how human valve cells respond to
      these printed environments. In this study, 3-D printable formulations of hybrid
      hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and
      methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits
      containing encapsulated human aortic valvular interstitial cells (HAVIC).
      Increasing Me-Gel concentration resulted in lower stiffness and higher viscosity,
      facilitated cell spreading, and better maintained HAVIC fibroblastic phenotype.
      Bioprinting accuracy was dependent upon the relative concentrations of Me-Gel and
      Me-HA, but when optimized enabled the fabrication of a trileaflet valve shape
      accurate to the original design. HAVIC encapsulated within bioprinted heart
      valves maintained high viability, and remodeled the initial matrix by depositing
      collagen and glyosaminoglycans. These findings represent the first rational
      design of bioprinted trileaflet valve hydrogels that regulate encapsulated human
      VIC behavior. The use of anatomically accurate living valve scaffolds through
      bioprinting may accelerate understanding of physiological valve cell interactions
      and progress towards de novo living valve replacements. 

PMID- 24334146
TI  - Synergy between Rho signaling and matrix density in cyclic stretch-induced stress
      fiber organization.
AB  - Cells adapt in response to mechanical stimulation to ensure adequate tissue
      functioning. F-actin stress fibers provide a key element in the adaptation
      process. The high sensitivity and fast adaptation of the F-actin cytoskeleton to
      cyclic strain have been studied extensively in a 2-D environment; however, 3-D
      data are scarce. Our previous work showed that stress fibers organize
      perpendicular to cyclic stretching (stretch-avoidance) in three dimensions.
      However, stretch-avoidance was absent when cells populated a high density matrix.
      In this study our aim was to obtain more insight into the synergy between matrix
      density and the signaling pathways that govern stress fiber remodeling. Therefore
      we studied stress fiber organization in 3-D reconstituted collagen tissues (at
      low and high matrix density), subjected to cyclic stretch upon interference with
      molecular signaling pathways. In particular, the influence of the small GTPase
      Rho and its downstream effectors were studied. Only at low matrix density does
      stress fiber stretch avoidance show a stretch-magnitude-dependent response. The
      activity of matrix metalloproteinases (MMPs), Rho-kinase and myosin light chain
      kinase are essential for stress fiber reorientation. Although high matrix density
      restricts stress fiber reorientation, Rho activation can overcome this
      restriction, but only in the presence of active MMPs. Results from this study
      highlight a synergistic action between matrix remodeling and Rho signaling in
      cyclic-stretch-induced stress fiber organization in 3-D tissue. 

PMID- 24334145
TI  - Bioactive self-assembled peptide nanofibers for corneal stroma regeneration.
AB  - Defects in the corneal stroma caused by trauma or diseases such as macular
      corneal dystrophy and keratoconus can be detrimental for vision. Development of
      therapeutic methods to enhance corneal regeneration is essential for treatment of
      these defects. This paper describes a bioactive peptide nanofiber scaffold system
      for corneal tissue regeneration. These nanofibers are formed by self-assembling
      peptide amphiphile molecules containing laminin and fibronectin inspired
      sequences. Human corneal keratocyte cells cultured on laminin-mimetic peptide
      nanofibers retained their characteristic morphology, and their proliferation was
      enhanced compared with cells cultured on fibronectin-mimetic nanofibers. When
      these nanofibers were used for damaged rabbit corneas, laminin-mimetic peptide
      nanofibers increased keratocyte migration and supported stroma regeneration.
      These results suggest that laminin-mimetic peptide nanofibers provide a promising
      injectable, synthetic scaffold system for cornea stroma regeneration. 

PMID- 24334147
TI  - Laser-structured bacterial nanocellulose hydrogels support ingrowth and
      differentiation of chondrocytes and show potential as cartilage implants.
AB  - The small size and heterogeneity of the pores in bacterial nanocellulose (BNC)
      hydrogels limit the ingrowth of cells and their use as tissue-engineered implant
      materials. The use of placeholders during BNC biosynthesis or post-processing
      steps such as (touch-free) laser perforation can overcome this limitation. Since
      three-dimensionally arranged channels may be required for homogeneous and
      functional seeding, three-dimensional (3-D) laser perforation of never-dried BNC
      hydrogels was performed. Never-dried BNC hydrogels were produced in different
      shapes by: (i) the cultivation of Gluconacetobacter xylinus (DSM 14666; synonym
      Komagataeibacter xylinus) in nutrient medium; (ii) the removal of bacterial
      residues/media components (0.1M NaOH; 30 min; 100  degrees C) and repeated
      washing (deionized water; pH 5.8); (iii) the unidirectional or 3-D laser
      perforation and cutting (pulsed CO2 Rofin SC * 10 laser; 220 MUm channel
      diameter); and (iv) the final autoclaving (2M NaOH; 121  degrees C; 20 min) and
      washing (pyrogen-free water). In comparison to unmodified BNC, unidirectionally
      perforated--and particularly 3-D-perforated - BNC allowed ingrowth into and
      movement of vital bovine/human chondrocytes throughout the BNC nanofiber network.
      Laser perforation caused limited structural modifications (i.e. fiber or globular
      aggregates), but no chemical modifications, as indicated by Fourier transform
      infrared spectroscopy, X-ray photoelectron scattering and viability tests. Pre
      cultured human chondrocytes seeding the surface/channels of laser-perforated BNC
      expressed cartilage-specific matrix products, indicating chondrocyte
      differentiation. 3-D-perforated BNC showed compressive strength comparable to
      that of unmodified samples. Unidirectionally or 3-D-perforated BNC shows high
      biocompatibility and provides short diffusion distances for nutrients and
      extracellular matrix components. Also, the resulting channels support migration
      into the BNC, matrix production and phenotypic stabilization of chondrocytes. It
      may thus be suitable for in vivo application, e.g. as a cartilage replacement
      material.

PMID- 24334148
TI  - Toll-like receptor 3 differently modulates inflammation in progressive or benign
      multiple sclerosis.
AB  - TLR-dependent signal transduction pathways were analyzed in patients with a
      diagnosis of either relapsing-remitting (RRMS), secondary progressive (PMS) or
      benign (BMS) MS and healthy controls (HC). Prototypical TLR molecules expressed
      either on the cell surface (TLR4) or intracellularly (TLR3) were stimulated with
      specific antigens (LPS and poly I:C, respectively). Expression of factors
      involved in TLR signaling cascades, production of downstream immune mediators and
      TLR expression were evaluated. Results showed that, whereas LPS-stimulation of
      TLR4 had a marginal effect on cell activation, poly I:C-stimulated TLR3
      expression on immune cells was significantly increased in PMS and BMS compared to
      HC. This was associated with a higher responsiveness to poly I:C that resulted in
      the activation of the TLR3-mediated pathway and the production of inflammatory
      cytokines in PMS and, in contrast, in the up-regulation of a peculiar mosaic of
      inflammation-dampening genes in BMS. Results herein might explain different MS
      disease phenotypes. 

PMID- 24334149
TI  - Neoplastic skin lesions of the scalp in children: a retrospective study of 265
      cases in Taiwan.
AB  - BACKGROUND: The preferential occurrence of certain skin neoplasms on the scalp of
      children raises concerns from their parents and warrants special diagnostic and
      therapeutic approaches. OBJECTIVE: To explore the demographic and clinical
      characteristics of scalp neoplasms in the pediatric population, with attention to
      malignant tumors and systemic syndromes. METHODS: Scalp neoplasms in patients
      aged 12 years or younger were retrospectively collected in 1990-2010 from two
      tertiary referral centers in Taiwan. RESULTS: A total of 267 scalp neoplasms in
      265 pediatric patients were recruited. Among the 209 neoplasms with a
      histopathological diagnosis, nevus sebaceus was the most common (67.9%), followed
      by melanocytic nevus (6.2%) and juvenile xanthogranuloma (6.2%). Most of the
      scalp neoplasms (77.9%) were seen at birth or before 1 month of age. Infantile
      hemangioma was clinically diagnosed without histology in 41.4% of cases.
      Malignant scalp tumors were identified in two patients (0.95%), with one basal
      cell carcinoma and one precursor B-cell lymphoblastic lymphoma, respectively.
      Scalp neoplasms in association with systemic syndromes were found in two cases.
      One had neurofibromatosis type I with juvenile xanthogranuloma and the other
      basal cell nevus syndrome with basal cell carcinoma. CONCLUSIONS: Most pediatric
      scalp neoplasms in our study were hamartomas or teratomas. Malignant scalp tumors
      and malignant transformation of nevus sebaceus were rare. A detailed medical
      history taking and complete physical examinations are needed to exclude possible
      associations with systemic syndromes or malignancies.

PMID- 24334150
TI  - Anilides and quinolones with nitrogen-bearing substituents from benzothiophene
      and thienothiophene series: synthesis, photochemical synthesis, cytostatic
      evaluation, 3D-derived QSAR analysis and DNA-binding properties.
AB  - A series of new anilides (2a-c, 4-7, 17a-c, 18) and quinolones (3a-b, 8a-b, 9a-b,
      10-15, 19) with nitrogen-bearing substituents from benzo[b]thiophene and
      thieno[2,3-c]thiophene series are prepared. Benzo[b]thieno[2,3-c]- and
      thieno[3',2':4,5]thieno[2,3-c]quinolones (3a-b, 8a-b) are synthesized by the
      reaction of photochemical dehydrohalogenation from corresponding anilides.
      Anilides and quinolones were tested for the antiproliferative activity. Fused
      quinolones bearing protonated aminium group, quaternary ammonium group, N
      methylated and protonated aminium group, amino and protonated amino group (8a,
      9b, 10-12) showed very prominent anticancer activity, whereby the hydrochloride
      salt of N',N'-dimethylaminopropyl-substituted quinolone (14) was the most active
      one, having the IC50 concentration at submicromolar range in accordance with
      previous QSAR predictions. On the other hand, flexible anilides were among the
      less active. Chemometric analysis of investigated compounds was performed. 3D
      derived QSAR analysis identified solubility, metabolitic stability and the
      possibility of the compound to be ionized at pH 4-8 as molecular properties that
      are positively correlated with anticancer activity of investigated compounds,
      while molecular flexibility, polarizability and sum of hydrophobic surface areas
      were found to be negatively correlated. Anilides 2a-b, 4-7 and quinolones 3a-b,
      8a-b, 9b and 10-14 were evaluated for DNA binding propensities and topoisomerases
      I/II inhibition as part of their mechanism of action. Among the anilides, only
      compound 7 presented some DNA binding propensity whereas the quinolones 8b, 9b
      and 10-14 intercalate in the DNA base pairs, compounds 8b, 9b and 14 being the
      most efficient ones. The strongest DNA intercalators, compounds 8b, 9b and 14,
      were clearly distinguished from the other compounds according to their molecular
      descriptors by the PCA and PLS analysis. 

PMID- 24334151
TI  - A new perspective on visual word processing efficiency.
AB  - As a fundamental part of our daily lives, visual word processing has received
      much attention in the psychological literature. Despite the well established
      advantage of perceiving letters in a word or in a pseudoword over letters alone
      or in random sequences using accuracy, a comparable effect using response times
      has been elusive. Some researchers continue to question whether the advantage due
      to word context is perceptual. We use the capacity coefficient, a well
      established, response time based measure of efficiency to provide evidence of
      word processing as a particularly efficient perceptual process to complement
      those results from the accuracy domain. 

PMID- 24334152
TI  - IgE and IgG epitope mapping by microarray peptide-immunoassay reveals the
      importance and diversity of the immune response to the IgG3 equine
      immunoglobulin.
AB  - The presence of whole horse IgG in therapeutic snake antivenom preparations of
      high purity is a contamination that can cause IgE-mediated allergic reactions in
      patients. In this study, the immunodominant IgE and IgG-binding epitopes in horse
      heavy chain IgG3 were mapped using arrays of overlapping peptides synthesized
      directly onto activated cellulose membranes. Pooled human sera from patients with
      and without horse antivenom allergies were used to probe the membrane. We have
      demonstrated that, for both cases, individuals produce antibodies to epitopes of
      sequential amino acids of horse heavy chain IgG3, although the signal strength
      and specificity appear to be distinct between the two groups of patients. A
      single region was found to contain the dominant allergic IgE epitope. The
      critical residues involved in the binding of human IgE to the epitope were
      determined to include four hydrophobic amino acids followed by polar and charged
      residues that formed a coil structure. This is the first study to describe the
      specific amino acid sequences involved with the immune recognition of human IgG
      and IgE to horse antivenom. 

PMID- 24334153
TI  - Burden of rotavirus gastroenteritis in children <5 years of age in Greece:
      hospital-based prospective surveillance (2008-2010).
AB  - OBJECTIVES: This study describes the epidemiology of rotavirus (RV)
      gastroenteritis (GE) disease following the introduction of RV vaccination in
      Greece in 2006. DESIGN: A prospective hospital-based surveillance. SETTING: A
      multicentre study was conducted at six hospitals in Greece between July 2008 and
      March 2010. The hospitals selected served 70% of the paediatric population in
      Greece. PARTICIPANTS: Children aged <5 years who visited the emergency rooms
      (ERs) or hospitalised with acute GE or acquired acute GE 48 h after
      hospitalisation and with a confirmed RV-positive stool test were enrolled.
      PRIMARY AND SECONDARY OUTCOME MEASURES: The occurrence of RVGE among all acute GE
      ER visits and hospitalisations and the occurrence of nosocomial RVGE are reported
      with 95% exact CI. Age-specific proportions of RVGE, seasonality and prevalence
      of RV genotypes were estimated. Incidence rates of nosocomial acute GE and RVGE
      are expressed in terms of 1000 children-years with 95% exact Poisson CI. Median
      duration of hospitalisation and prolongation of hospitalisation due to nosocomial
      RVGE were reported. RESULTS: RVGE proportions were 10.7% (95% CI 5.5% to 18.3%)
      and 23.8% (95% CI 20.0% to 28.0%) of acute GE ER visits and hospitalisations,
      respectively; and 21.6% (95% CI 9.8% to 38.2%) of nosocomial acute GE cases. The
      majority of RVGE cases occurred in children aged <24 months (53%). RV infection
      peaked between December and May (31.4%). The most common RV genotypes were G4
      (59.6%) and P[8] (75.2%). The median duration of RVGE hospitalisation was 4 days
      (range 1-10 days). Incidence of nosocomial RVGE was 0.3 (95% CI 0.2 to 0.7)/1000
      children-years. The median prolongation of hospitalisation due to nosocomial RVGE
      was 5 days (range 4-7 days). CONCLUSIONS: Our analysis report low proportions of
      RVGE among acute GE cases in Greece which may be attributable to available RV
      vaccination in Greece. Future impact/effectiveness studies are necessary to
      confirm this finding. CLINICAL TRIAL REGISTRATION: NCT00751686.

PMID- 24334154
TI  - Polytobacco use and multiple-product smoking among a random community sample of
      African-American adults.
AB  - OBJECTIVES: Little is known about polytobacco use among African-American adults.
      This study is the first to explore this among a random, statewide, community
      sample of African-American adults. SETTING: Community-based sampling obtained a
      random, household-probability sample of African-American adults from California,
      surveyed door to door in randomly selected census tracts statewide. PARTICIPANTS:
      Participants were a statewide, random-household sample of N=2118 African-American
      adults from California who completed a survey on past 30-day smoking of
      cigarettes, blunts, bidis, kreteks, cigarillos, marijuana and cigars. RESULTS:
      Almost half (49.3%) of the African-American cigarette-smokers and 14.9% of the
      cigarette non-smokers had smoked at least one non-cigarette product in the past
      30 days. Smokers had a substantial prevalence of smoking cigarillos (28.7%) and
      blunts (27.7%). Logistic regressions revealed that the odds of smoking most of
      the non-cigarette products were higher for cigarette smokers and men, inversely
      related to age, and unrelated to socioeconomic status. However, smoking of
      blunts, bidis and kreteks was not predicted by cigarette smoking. CONCLUSIONS:
      Smoking of cigarillos (eg, Phillies, Black & Mild) and blunts may be prevalent
      among African-American cigarette-smokers and non-smokers alike, but such products
      are not examined in most population-level smoking research. Smoking of these
      products should be included in surveillance studies, in cancer prevention
      programmes and in healthcare provider-assessment of smoking, and addressed in
      smoking cessation programmes as well.

PMID- 24334155
TI  - Maternal post-traumatic stress disorder, depression and alcohol dependence and
      child behaviour outcomes in mother-child dyads infected with HIV: a longitudinal
      study.
AB  - OBJECTIVES: HIV and psychiatric disorders are prevalent and often concurrent.
      Childbearing women are at an increased risk for both HIV and psychiatric
      disorders, specifically depression and post-traumatic stress disorder (PTSD).
      Poor mental health in the peripartum period has adverse effects on infant
      development and behaviour. Few studies have investigated the relationship between
      maternal PTSD and child behaviour outcomes in an HIV vertically infected sample.
      The aim of this study was to investigate whether maternal postpartum trauma
      exposure and PTSD were risk factors for child behaviour problems. In addition,
      maternal depression, alcohol abuse and functional disability were explored as
      cofactors. SETTING: The study was conducted in Cape Town, South Africa.
      PARTICIPANTS: 70 mother-child dyads infected with HIV were selected from a group
      of participants recruited from community health centres. DESIGN: The study
      followed a longitudinal design. Five measures were used to assess maternal trauma
      exposure, PTSD, depression, alcohol abuse and functional disability at 12 months
      postpartum: Life Events Checklist (LEC), Harvard Trauma Scale (HTS), Alcohol Use
      Disorders Identification Test (AUDIT), Center for Epidemiological Studies
      Depression (CESD) Scale and the Sheehan Disability Scale (SDS). Child behaviour
      was assessed at 42 months with the Child Behaviour Checklist (CBCL). RESULTS: The
      rate of maternal disorder was high with 50% scoring above the cut-off for
      depression, 22.9% for PTSD and 7% for alcohol abuse. Half of the children scored
      within the clinical range for problematic behaviour. Children of mothers with
      depression were significantly more likely to display total behaviour problems
      than children of mothers without depression. Maternal PTSD had the greatest
      explanatory power for child behaviour problems, although it did not significantly
      predict child outcomes. CONCLUSIONS: This study highlights the importance of
      identifying and managing maternal PTSD and depression in mothers of children
      infected with HIV. The relationship between maternal PTSD and child behaviour
      warrants further investigation.

PMID- 24334156
TI  - Medical students' knowledge, attitudes and perceptions towards contraceptive use
      and counselling: a cross-sectional survey in Maharashtra, India.
AB  - OBJECTIVES: This study aimed to investigate the knowledge, attitudes and
      perceptions towards contraceptive use and counselling among medical students in
      Maharashtra, India. SETTING: Considerable global maternal mortality and morbidity
      could be avoided through the use of effective contraception. In India,
      contraception services are frequently unavailable or there are obstacles to
      obtaining modern, reversible contraceptives. PARTICIPANTS: A cross-sectional
      descriptive study using a self-administered questionnaire was conducted among
      1996 medical students in their fifth year of study at 27 medical colleges in the
      state of Maharashtra, India. Descriptive and analytical statistics interpreted
      the survey instrument and significant results were presented with 95% CI.
      RESULTS: Respondents expressed a desire to provide contraceptive services. A few
      students had experienced training in abortion care. There were misconceptions
      about modern contraceptive methods and the impact of sex education. Attitudes
      towards contraception were mainly positive, premarital counselling was supported
      and the influence of traditional values and negative provider attitudes on
      services was recognised. Gender, area of upbringing and type of medical college
      did not change the results. CONCLUSIONS: Despite mostly positive attitudes
      towards modern contraceptives, sex education and family planning counselling,
      medical students in Maharashtra have misconceptions about modern methods of
      contraception. Preservice and in-service training in contraceptive counselling
      should be implemented in order to increase women's access to evidence-based
      maternal healthcare services.

PMID- 24334157
TI  - Long-term trajectories of back pain: cohort study with 7-year follow-up.
AB  - OBJECTIVE: To describe long-term trajectories of back pain. DESIGN: Monthly data
      collection for 6 months at 7-year follow-up of participants in a prospective
      cohort study. SETTING: Primary care practices in Staffordshire, UK. PARTICIPANTS:
      228 people consulting their general practitioners with back pain, on whom
      information on 6-month back pain trajectories had been collected during 2001
      2003, and who had valid consent and contact details in 2009-2010, were contacted.
      155 participants (68% of those contacted) responded and provided sufficient data
      for primary analyses. OUTCOME MEASURES: Trajectories based on patients' self
      reports of back pain were identified using longitudinal latent class analysis.
      Trajectories were characterised using information on disability, psychological
      status and presence of other symptoms. RESULTS: Four clusters with different back
      pain trajectories at follow-up were identified: (1) no or occasional pain, (2)
      persistent mild pain, (3) fluctuating pain and (4) persistent severe pain.
      Trajectory clusters differed significantly from each other in terms of
      disability, psychological status and other symptoms. Most participants remained
      in a similar trajectory as 7 years previously (weighted kappa 0.54; 95% CI 0.42
      to 0.65). CONCLUSIONS: Most people with back pain appear to follow a particular
      pain trajectory over long time periods, and do not have frequently recurring or
      widely fluctuating patterns. The results are limited by lack of information about
      the time between data collection periods and by loss to follow-up. However,
      findings do raise questions about standard divisions into acute and chronic back
      pain. A new framework for understanding the course of back pain is proposed.

PMID- 24334159
TI  - Effectiveness of continence promotion for older women via community
      organisations: a cluster randomised trial.
AB  - OBJECTIVES: The primary objective of this cluster randomised controlled trial was
      to compare the effectiveness of the three experimental continence promotion
      interventions against a control intervention on urinary symptom improvement in
      older women with untreated incontinence recruited from community organisations. A
      second objective was to determine whether changes in incontinence-related
      knowledge and new uptake of risk-modifying behaviours explain these improvements.
      SETTING: 71 community organisations across the UK. PARTICIPANTS: 259 women aged
      60 years and older with untreated incontinence entered the trial; 88% completed
      the 3-month follow-up. INTERVENTIONS: The three active interventions consisted of
      a single 60 min group workshop on (1) continence education (20 clusters, 64
      women); (2) evidence-based self-management (17 clusters, 70 women); or (3)
      combined continence education and self-management (17 clusters, 61 women). The
      control intervention was a single 60 min educational group workshop on memory
      loss, polypharmacy and osteoporosis (17 clusters, 64 women). PRIMARY AND
      SECONDARY OUTCOME MEASURES: The primary outcome was self-reported improvement in
      incontinence 3 months postintervention at the level of the individual. The
      secondary outcome was change in the International Consultation on Incontinence
      Questionnaire (ICIQ) from baseline to 3-month follow-up. Changes in incontinence
      related knowledge and behaviours were also assessed. RESULTS: The highest rate of
      urinary symptom improvement occurred in the combined intervention group (66% vs
      11% of the control group, prevalence difference 55%, 95% CI 43% to 67%,
      intracluster correlation 0). 30% versus 6% of participants reported significant
      improvement respectively (prevalence difference 23%, 95% CI 10% to 36%,
      intracluster correlation 0). The number-needed-to-treat was 2 to achieve any
      improvement in incontinence symptoms, and 5 to attain significant improvement.
      Compared to controls, participants in the combined intervention reported an
      adjusted mean 2.05 point (95% CI 0.87 to 3.24) greater improvement on the ICIQ
      from baseline to 3-month follow-up. Changes in knowledge and self-reported risk
      reduction behaviours paralleled rates of improvement in all intervention arms.
      CONCLUSIONS: Continence education combined with evidence-based self-management
      improves symptoms of incontinence among untreated older women. Community
      organisations represent an untapped vector for delivering effective continence
      promotion interventions. TRIAL REGISTRATION: ClinicalTrials.gov ID number
      NCT01239836.

PMID- 24334158
TI  - Thromboprophylaxis only during hospitalisation in fast-track hip and knee
      arthroplasty, a prospective cohort study.
AB  - OBJECTIVES: International guidelines recommend thrombosis prophylaxis after total
      hip arthroplasty (THA) and total knee arthroplasty (TKA) for up to 35 days.
      However, previous studies often have hospital stays (length of stay; LOS) of 8-12
      days and not considering early mobilisation, which may reduce incidence of venous
      thromboembolic events (VTE). We investigated the incidence of any symptomatic
      thromboembolic events (TEEs) with only in-hospital prophylaxis if LOS <=5 days
      after fast-track THA and TKA. DESIGN: A prospective descriptive multicentre
      cohort study in fast-track THA and TKA from February 2010 to December 2011, with
      complete 90-day follow-up through the Danish National Patient Registry and
      patient files. SETTING: 6 Danish high-volume centres with a similar standardised
      fast-track setup, including spinal anaesthesia, opioid-sparing analgesia, early
      mobilisation, functional discharge criteria and discharge to own home.
      PARTICIPANTS: 4924 consecutive unselected unilateral primary THA and TKAs in
      patients >=18 years with no preoperative use of continuous 'potent'
      anticoagulative therapy (vitamin K antagonists). EXPOSURE: Prophylaxis with low
      molecular-weight heparin or factor Xa-inhibitors only during hospitalisation when
      LOS <=5 days. OUTCOMES: Incidence of symptomatic TEE-related, VTE-related and VTE
      related mortality <=90 days postoperatively. RESULTS: LOS <=5 days and
      thromboprophylaxis only during hospitalisation occurred in 4659 procedures (94.6%
      of total). Median LOS and prophylaxis duration was 2 days (IQR 2-3) with 0.84%
      (95% CI 0.62% to 1.15%) TEE and 0.41% (0.26% to 0.64%) VTE during 90-day follow
      up. VTE consisted of five pulmonary embolisms (0.11% (0.05% to 0.25%)) and 14
      deep venous thrombosis (0.30% (0.18% to 0.50%)). There were four (0.09% (0.04% to
      0.23%)) surgery-related deaths, of which 1 (0.02% (0.00% to 0.12%)) was due to
      pulmonary embolism, and 6 (0.13% (0.06% to 0.28%)) deaths of unknown causes after
      discharge. CONCLUSIONS: The low incidence of TEE and VTE suggests that in
      hospital prophylaxis only, is safe in fast-track THA and TKA patients with LOS of
      <=5 days. Guidelines on thromboprophylaxis may need reconsideration in fast-track
      elective surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01557725.

PMID- 24334160
TI  - Examining the latent structure of worry and generalized anxiety in a clinical
      sample.
AB  - Generalized anxiety disorder (GAD) is characterized by "pathological" worry,
      suggesting that GAD worriers differ qualitatively from non-GAD worriers. However,
      results from taxometric studies of worry in undergraduate and community samples
      have been mixed and to date, no studies have utilized clinical samples. The
      current study examined the latent structure of worry and GAD symptoms in a
      diagnostically heterogeneous clinical sample. Indicators were selected from the
      Penn State Worry Questionnaire-Abbreviated (n=1175) and the GAD-7 (n=638) and
      submitted to three taxometric procedures: MAXCOV, MAMBAC, and L-Mode. Results
      from all three procedures suggested that both worry and generalized anxiety are
      best conceptualized as dimensional constructs. Findings also indicated that
      ongoing conceptualization, assessment, and treatment of worry and GAD may be
      hampered by the application of a categorical framework. 

PMID- 24334162
TI  - Ethnobotanical study of medicinal plants used by Tai Yai in Northern Thailand.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: We studied traditional knowledge of medicinal
      plants used by Tai Yai people in Northern Thailand. We documented traditional
      medical practices and determined importance among the Tai Yai. This paper reports
      on knowledge in usage of medicinal plants of the Tai Yai people in Northern
      Thailand. MATERIALS AND METHODS: Interviews were conducted in 4 Tai Yai villages
      in Mae Hong Son and Chiang Mai provinces whose inhabitants immigrated from
      Myanmar at different times. Discussions and interviews were held with 126 key
      informants (56 males and 70 females) ranging in age from 16 to 80 years in three
      age groups (age 16-40, 41-60, and 61-80). We calculated the informant consensus
      factor (ICF) for use category, use value index (UV) for use report of plant. We
      tested differences between the knowledge of different age groups and locations
      using principal component analysis (PCA). RESULTS: These Tai Yai people used of
      141 medicinal plants belonging to 59 families. Of the medicinal plant species,
      the highest percentage was in the family Euphorbiaceae: Croton acutifolius and
      Croton roxburghii. The highest number of Informant consensus factor was for
      metabolic system disorders. Overall, Tai Yai people use medicinal plants to cure
      many sicknesses such as hypertension, lumbago, wounds, puerperium, kidney
      disorders, kidney stones, coughs, fevers, hemorrhoids, flatulence and malaria.
      There were no significant differences in knowledge of plants usage among villages
      of different ages. In addition, the knowledge of the plants was not significantly
      different between men and women. However, we found that the younger had less
      experience with and knowledge of medicinal plants than older people. CONCLUSIONS:
      The result indicates loss of accumulated knowledge of medicinal plants and
      traditional use. Although, the medicinal plant knowledge was passed from one
      generation to the next by word of mouth, the detailed documentation of medicinal
      plants and their use may effectively prevent the knowledge-loss through time.

PMID- 24334163
TI  - Comparative pharmacokinetics and the bioavailability of escin Ib and isoescin Ib
      following the administration of escin, pure escin Ib and isoescin Ib in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Adequate pharmacokinetic data of escin, a natural
      mixture of triterpene saponins used for the treatment of chronic venous
      insufficiency, hemorrhoids, inflammation and edema, is of special interest in
      view of the growing use of escin agent in clinical medicine. However,
      pharmacokinetic data are inadequate to support their clinical indication. Escin
      Ib and isoescin Ib are the chief active ingredients in escin, pharmacokinetics
      study of them would be helpful for improving the practice of escin application.
      The goals of this study are to determine the plasma concentration of escin Ib and
      isoescin Ib using an established liquid chromatography tandem mass spectrometry
      (LC-MS/MS) method and to compare the pharmacokinetics and bioavailability of
      these compounds in rats when administered as pure isomers or as sodium escinate.
      MATERIALS AND METHODS: Five groups of Wistar rats (n=6 per group) were treated
      with either an intravenous (IV) dose (2.78mg/kg) of sodium escinate
      (corresponding to 0.5mg/kg of escin Ib and 0.5mg/kg of isoescin Ib), an IV dose
      (0.5mg/kg) and an oral dose (4mg/kg) of pure escin Ib or isoescin Ib. The
      concentrations of escin Ib and isoescin Ib in rat plasma were determined by LC
      MS/MS at various times following the administration of the drugs. The
      pharmacokinetic parameters were estimated by a non-compartmental analysis and
      then subjected to statistical analysis. RESULTS: The administration of sodium
      escinate, which contains the two isomers, gave rise to higher terminal phase half
      life (t1/2) and mean residence time (MRT) values for both escin Ib and isoescin
      Ib compared to the corresponding compounds administered alone. The absorption of
      escin Ib and isoescin Ib was very poor, with the oral bioavailability (F) values
      of <2% observed for both compounds. The two compounds were found to isomerize in
      vivo, wherein the conversion of escin Ib to isoescin Ib was much easier than that
      of isoescin Ib to escin Ib. CONCLUSIONS: A comparison of the pharmacokinetics of
      escin Ib and isoescin Ib administered alone and together in rats suggests that
      the administration of herbal preparations of escin in a clinical setting may
      result in a longer duration of action than the administration of each isomer
      alone. The interconversion of escin Ib and isoescin Ib when administered alone
      indicates that the administration of one isomer results in exposure to the other
      isomer.

PMID- 24334161
TI  - A person-centered analysis of posttraumatic stress disorder symptoms following a
      natural disaster: predictors of latent class membership.
AB  - The present study applied latent class analysis to a sample of 810 participants
      residing in southern Mississippi at the time of Hurricane Katrina to determine if
      people would report distinct, meaningful PTSD symptom classes following a natural
      disaster. We found a four-class solution that distinguished persons on the basis
      of PTSD symptom severity/pervasiveness (Severe, Moderate, Mild, and Negligible
      Classes). Multinomial logistic regression models demonstrated that membership in
      the Severe and Moderate Classes was associated with potentially traumatic
      hurricane-specific experiences (e.g., being physically injured, seeing dead
      bodies), pre-hurricane traumatic events, co-occurring depression symptom severity
      and suicidal ideation, certain religious beliefs, and post-hurricane stressors
      (e.g., social support). Collectively, the findings suggest that more
      severe/pervasive typologies of natural disaster PTSD may be predicted by the
      frequency and severity of exposure to stressful/traumatic experiences (before,
      during, and after the disaster), co-occurring psychopathology, and specific
      internal beliefs. 

PMID- 24334164
TI  - Octopamine and Dopamine differentially modulate the nicotine-induced calcium
      response in Drosophila Mushroom Body Kenyon Cells.
AB  - In Drosophila associative olfactory learning, an odor, the conditioned stimulus
      (CS), is paired to an unconditioned stimulus (US). The CS and US information
      arrive at the Mushroom Bodies (MB), a Drosophila brain region that processes the
      information to generate new memories. It has been shown that olfactory
      information is conveyed through cholinergic inputs that activate nicotinic
      acetylcholine receptors (nAChRs) in the MB, while the US is coded by biogenic
      amine (BA) systems that innervate the MB. In this regard, the MB acts as a
      coincidence detector. A better understanding of the properties of the responses
      gated by nicotinic and BA receptors is required to get insights on the cellular
      and molecular mechanisms responsible for memory formation. In recent years,
      information has become available on the properties of the responses induced by
      nAChR activation in Kenyon Cells (KCs), the main neuronal MB population. However,
      very little information exists on the responses induced by aminergic systems in
      fly MB. Here we have evaluated some of the properties of the calcium responses
      gated by Dopamine (DA) and Octopamine (Oct) in identified KCs in culture. We
      report that exposure to BAs induces a fast but rather modest increase in
      intracellular calcium levels in cultured KCs. The responses to Oct and DA are
      fully blocked by a VGCC blocker, while they are differentially modulated by cAMP.
      Moreover, co-application of BAs and nicotine has different effects on
      intracellular calcium levels: while DA and nicotine effects are additive, Oct and
      nicotine induce a synergistic increase in calcium levels. These results suggest
      that a differential modulation of nicotine-induced calcium increase by DA and Oct
      could contribute to the events leading to learning and memory in flies. 

PMID- 24334165
TI  - SA4503, a sigma-1 receptor agonist, suppresses motor neuron damage in in vitro
      and in vivo amyotrophic lateral sclerosis models.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
      Recently, it has been reported that a mutation in the sigma-1 receptor causes
      juvenile ALS. Therefore, the function of the sigma-1 receptor may be important in
      the pathology of ALS. In the present study, we investigated the effect of SA4503,
      a sigma-1 receptor agonist, against in in vitro and in vivo ALS models. We first
      investigated whether SA4503, a sigma-1 receptor agonist, prevented superoxide
      dismutase 1 (SOD1(G93A))- and serum free-induced cell death of mice motor neuron
      cells (NSC34) in in vitro model of an ALS. At concentrations of 1-10MUM, SA4503
      reduced SOD1(G93A)-induced cell death in a concentration-dependent manner, and
      BD1047, a sigma-1 receptor antagonist, inhibited the protective effect of SA4503.
      Next, we investigated whether SA4503 affected the phosphorylation levels of Akt
      (Ser 473) and extracellular signal-regulated kinase (ERK) 1/2 and the expression
      of the sigma-1 receptor. SA4503 promoted the phosphorylation of Akt (Ser 473) and
      ERK1/2 in a time-dependent manner, but SA4503 did not affect the expression of
      the sigma-1 receptor. These results suggest that the protective effect of SA4503
      might be involved in promoting the phosphorylation of Akt and ERK1/2. We then
      investigated whether SA4503 suppressed the progression of ALS in an SOD1(G93A)
      ALS mouse model. SA4503 did not affect the onset time of ALS. However, it
      significantly extended the survival time in the SOD1(G93A) mice compared with a
      vehicle-treated group. These findings indicate that SA4503 is effective in
      suppressing motor neuron degeneration and symptom progression in ALS. 

PMID- 24334166
TI  - Urinary BDNF-to-creatinine ratio is associated with aerobic fitness.
AB  - Circulating levels of brain-derived neurotrophic factor (BDNF) are known to be
      affected by aerobic exercise. As the previous research focus in humans has been
      to examine peripheral BDNF levels through blood, serum, and platelet assay, the
      present study investigated the association between basal urinary BDNF
      concentration and indices of aerobic fitness in a sample of young adults (n=52).
      Aerobic fitness was evaluated with self-report of exercise habits and heart rate
      (HR) assessment during a sub-maximal Step Test. BDNF concentration was determined
      by enzyme-linked immunosorbent assay and adjusted for creatinine. Results
      indicated that the basal BDNFlog/creatinine ratio was positively associated with
      greater frequency of exercise and, during aerobic challenge, a quicker rise in HR
      upon exercise, lower peak HR during exercise, and lower HR during the recovery
      period, each indicative of enhanced fitness. These results highlight the utility
      of urine capture as a non-invasive technique to assess for exercise-mediated
      changes in peripheral BDNF. 

PMID- 24334167
TI  - Preparing to approach or avoid alcohol: EEG correlates, and acute alcohol
      effects.
AB  - Recently an approach-bias for alcohol has been described as an important
      cognitive motivational process in the etiology of alcohol use problems. In the
      approach-bias, perception and action are inextricably linked and stimulus
      response associations are central to this bias: performance improves when task
      instructions are congruent with a pre-existing stimulus-response association.
      These pre-existing response associations could potentially allow advance response
      preparation and execution. The present study aimed at investigating the effect of
      the alcohol approach bias on response preparation by means of event-related
      desynchronization in the beta band (beta-ERD) of the EEG signal and the effect of
      acute alcohol in the approach bias in response to alcohol cues. Subjects (18
      social drinkers) performed an adapted alcohol-Approach Avoidance Task, in which a
      preparatory period was provided between alcohol/soft drink cues and
      approach/avoid responses. Subjects were tested both in a placebo and in an
      alcohol condition (counterbalanced). Posterior beta-ERD was found to increase
      during preparation for alcohol-approach trials. The beta-ERD in the congruent
      block increased following alcohol administration. These results suggest that
      advance response preparation may play a role in the alcohol approach bias and
      that acute alcohol facilitates response preparatory processes for approach
      alcohol trials. Future EEG studies using the adapted AAT may help understanding
      approach biases in addiction. 

PMID- 24334168
TI  - Low grade cirrhosis induces cognitive impairment and motor dysfunction in rats:
      could be a model for minimal hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a nervous system disorder developed in the
      patients with liver cirrhosis. The low grade cirrhosis is of common occurrence,
      however, whether and the extent to which it affects brain function is not clearly
      understood. The present article examines certain neurobehavioral parameters in
      the rats with low grade chronic liver failure (CLF) induced by intraperitoneal
      administration of 50mg/kgb.w. thioacetamide up to 14 days. During Morris Water
      Maze tasks, the CLF rats, as compared to the control, showed insignificant
      decline in the escape latency score to find out the hidden platform throughout
      the learning days and also stayed for a significantly declined (p<0.01) time
      period at the place of the hidden platform during the retrieval test. They also
      showed impairment in the conditional discrimination ability, reflected by a
      significant decline in the active avoidance score (p<0.05) and increment in the
      number of non-response (p<0.05) during shuttle box tests. On rotarod performance,
      they exhibited significant decline in their riding time (p<0.01-001) on the
      rotating rod as a function of increasing speed. The findings suggest a moderate
      level cognitive impairment and motor dysfunction in the low grade CLF rats.
      Since, these impairments correlate with the early stage manifestation of HE in
      the patients, these CLF rats could serve as a model to study the pathogenesis of
      minimal hepatic encephalopathy. 

PMID- 24334169
TI  - Statistical shape and appearance models of bones.
AB  - When applied to bones, statistical shape models (SSM) and statistical appearance
      models (SAM) respectively describe the mean shape and mean density distribution
      of bones within a certain population as well as the main modes of variations of
      shape and density distribution from their mean values. The availability of this
      quantitative information regarding the detailed anatomy of bones provides new
      opportunities for diagnosis, evaluation, and treatment of skeletal diseases. The
      potential of SSM and SAM has been recently recognized within the bone research
      community. For example, these models have been applied for studying the effects
      of bone shape on the etiology of osteoarthritis, improving the accuracy of
      clinical osteoporotic fracture prediction techniques, design of orthopedic
      implants, and surgery planning. This paper reviews the main concepts, methods,
      and applications of SSM and SAM as applied to bone. 

PMID- 24334170
TI  - Perinatal hypophosphatasia caused by uniparental isodisomy.
AB  - Hypophosphatasia (HPP) is an inherited disorder characterized by defective bone
      mineralization caused by mutations in the alkaline phosphatase gene (ALPL).
      Clinically, the disease spans a great continuum of disease severity and six forms
      can be distinguished according to the age of onset. The most severe is the
      autosomal recessive perinatal form, a major prenatal skeletal dysplasia in Japan.
      The ALPL mutation c.1559delT causes perinatal HPP and occurs frequently in the
      Japanese. Most patients with perinatal HPP in Japan are homozygous for
      c.1559delT, and their parents are usually heterozygous with no evidence of
      consanguinity. Here we identified a fetus with perinatal HPP resulting from an
      unusual mechanism known as paternal uniparental isodisomy (UPD) of chromosome 1.
      Sequence analysis of ALPL in the patient revealed the presence of the homozygous
      mutation c.1559delT. We suspected UPD because the father and mother were
      heterozygous and wild type, respectively. Analysis of polymorphic microsatellite
      markers spanning chromosome 1 and whole-genome arrays revealed a uniparental
      inheritance from the father and excluded deletions or de novo mutations. This is
      the first description of perinatal HPP caused by UPD. This report also emphasizes
      the low recurrence risk of a non-Mendelian inheritance pattern in UPD and the
      value of determining parental genotypes with homozygous mutations in a patient to
      confirm whether the condition is caused by UPD or not, even when the mutation is
      detected as a hot spot, as described in the literature. 

PMID- 24334171
TI  - Linkage and association analyses using families identified a locus affecting an
      osteoporosis-related trait.
AB  - Osteoporosis is a common disorder characterized by low bone mass and
      microarchitectural deterioration of bone tissue, resulting in an increase in bone
      fragility and in susceptibility to fractures. The genetic basis of osteoporosis
      is complex and involves multiple genes and environmental factors. Here we
      introduce a family-based study of the genetics of osteoporosis - the Genetic
      Analysis of Osteoporosis (GAO) Project - to discover genetic variants affecting
      osteoporosis-related phenotypes. The GAO Project involved 11 extended families
      from Barcelona, Spain selected through a proband with osteoporosis (N=367). We
      performed spine, femur and whole body densitometry for all participants and also
      analyzed strength and geometrical properties of the hip. Our study focused on 23
      densitometric phenotypes that we considered of high clinical relevance and four
      definitions of low bone mass and fracture status. Pedigree validation was carried
      out through microsatellite genotyping. The same microsatellites were used to
      interrogate our data (i) for the replication of previous linkage signals and (ii)
      for the potential discovery of new linkage signals. The linkage analysis
      identified one region marked by microsatellite D17S787 showing a strong and
      significant signal of linkage with femoral shaft cross-sectional moment of
      inertia (CSMI; LOD=3.18; p=6.5*10(-5)). The chromosomal location marked by
      microsatellite D17S787 includes several genes, among which two are of particular
      interest: COL1A1 and SOST, coding for collagen alpha-1 (I) chain and sclerostin,
      respectively. Follow-up association analysis resulted in only one significant
      result for rs4792909 from the SOST genomic region (p=0.00248). As a result, we
      provide strong and significant evidence from both linkage and association
      analyses that the SOST gene may affect the strength of the femoral shaft. Future
      investigations should study the relationship between bone mass formation and
      strength properties of the bones. 

PMID- 24334172
TI  - Enhanced detection and desalting free protocol for phosphopeptides eluted from
      immobilized Fe (III) affinity chromatography in direct MALDI TOF analysis.
AB  - IMAC strategy is widely used in phosphopeptide enrichment, but most of the
      current eluents contain large amount of salt, which must be discarded before MS
      detection. Here, we present techniques to elute phosphopeptides with low
      ionization efficiency reagents, which could be left in the eluate for direct MS
      analysis, thus saving desalting and the following steps. Several reagents were
      studied, including 5-sulfosalicylic acid dihydrate, acetyl acetone and
      glyphosate. The results show that glyphosate has very outstanding advantages:
      only monophosphopeptides can be eluted with glyphosate solution, while all
      phosphopeptides can be eluted with negatively charged glyphosate ions with pH9.
      Moreover, the high ionic strength can minimize nonspecific electrostatic
      interactions in elution step and limit the generation of potential phosphopeptide
      metal ion adducts such as sodium or Fe(3+) counterparts. S/N of phosphopeptides
      could be enhanced 3-5 folds in MALDI MS detection and phosphopeptide recovery is
      greatly improved while compared with its counterparts eluted by commonly used
      elution buffers. By applying this reagent into IMAC elution, the whole
      experimental process could be more convenient, time-saving and cost-saving, which
      is of great importance to the enrichment and detection of phosphopeptides in
      phosphoproteomics research. BIOLOGICAL SIGNIFICANCE: This potent desalting-free
      and signal enhanced elution method can improve the sensitivity and detection of
      phosphopeptides in MALDI TOF MS analysis, both time saving and cost saving. With
      these advantages, it's highly appropriate for the high throughout analysis of
      phosphoproteomics.

PMID- 24334173
TI  - Effect of surfactant types and their concentration on the structural
      characteristics of nanoclay.
AB  - A series of organo-modified nanoclays was synthesized using three different
      surfactants having different alkyl chain lengths and concentrations [0.5-5.0
      cation exchange capacity (CEC)]. These surfactants were Ethanolamine (EA),
      Cetyltrimethylammoniumbromide (CTAB) and Tetraoctadecylammoniumbromide (TO). The
      obtained modified nanoclays were characterized by X-ray diffraction (XRD),
      Fourier Transform Infrared spectroscopy (FTIR) and Scanning electron microscopy
      (SEM) and compared with unmodified nanoclay. The results of XRD analysis
      indicated that the basal d-spacing has increased with increasing alkyl chain
      length and surfactant concentration. From the obtained microstructures of these
      organo-modified nanoclays, the mechanism of surfactant adsorption was proposed.
      At relatively low loading of surfactant, most of surfactant entered the spacing
      by an ion-exchange mechanism and is adsorbed onto the interlayer cation sites.
      When the concentration of the surfactant exceeds the CEC of clay, the surfactant
      molecules then adhere to the surface adsorbed surfactant. Some surfactants
      entered the interlayers, whereas the others were attached to the clay surface.
      When the concentration of surfactant increased further beyond 2.0 CEC, the
      surfactants might occupy the inter-particle space within the house-of-cards
      aggregate structure. 

PMID- 24334174
TI  - Sodium glucose transport 2 (SGLT2) inhibition decreases glomerular
      hyperfiltration: is there a role for SGLT2 inhibitors in diabetic kidney disease?

PMID- 24334175
TI  - Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients
      with type 1 diabetes mellitus.
AB  - BACKGROUND: The primary objective of this mechanistic open-label, stratified
      clinical trial was to determine the effect of 8 weeks' sodium glucose
      cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration
      in subjects with type 1 diabetes mellitus (T1D). METHODS AND RESULTS: Inulin
      (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma
      flow) clearances were measured in individuals stratified based on having
      hyperfiltration (T1D-H, GFR >= 135 mL/min/1.73m(2), n=27) or normal GFR (T1D-N,
      GFR 90-134 mL/min/1.73m(2), n=13) at baseline. Renal function and circulating
      levels of renin-angiotensin-aldosterone system mediators and NO were measured
      under clamped euglycemic (4-6 mmol/L) and hyperglycemic (9-11 mmol/L) conditions
      at baseline and end of treatment. During clamped euglycemia, hyperfiltration was
      attenuated by -33 mL/min/1.73m(2) with empagliflozin in T1D-H, (GFR 172+/-23
      139+/-25 mL/min/1.73 m(2), P<0.01). This effect was accompanied by declines in
      plasma NO and effective renal plasma flow and an increase in renal vascular
      resistance (all P<0.01). Similar significant effects on GFR and renal function
      parameters were observed during clamped hyperglycemia. In T1D-N, GFR, other renal
      function parameters, and plasma NO were not altered by empagliflozin.
      Empagliflozin reduced hemoglobin A1c significantly in both groups, despite lower
      insulin doses in each group (P<=0.04). CONCLUSIONS: In conclusion, short-term
      treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin
      attenuated renal hyperfiltration in subjects with T1D, likely by affecting
      tubular-glomerular feedback mechanisms. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01392560.

PMID- 24334176
TI  - Visible age-related signs and risk of ischemic heart disease in the general
      population: a prospective cohort study.
AB  - BACKGROUND: Cardiovascular disease is 1 of the most common age-related diseases,
      and also 1 of the most common causes of death in the general population. We
      tested the hypothesis that visible age-related signs associate with risk of
      ischemic heart disease (IHD), myocardial infarction (MI), and death in the
      general population, independent of chronological age. METHODS AND RESULTS: 10,885
      individuals aged 20 to 93 years free of IHD were followed from 1976 through 1978
      until June 2011 with 100% complete follow-up. During these 35 years of follow-up,
      3401 participants developed IHD and 1708 developed MI. Presence of frontoparietal
      baldness, crown top baldness, earlobe crease, and xanthelasmata was associated
      with increased risk of IHD or MI after multifactorial adjustment for
      chronological age and well-known cardiovascular risk factors. The risk of IHD and
      MI increased stepwise with increasing number of age-related signs with
      multifactorially adjusted hazard ratios up to 1.40 (95% confidence interval, 1.20
      1.62) for IHD and 1.57 (1.28-1.93) for MI, in individuals with 3 to 4 versus no
      age-related signs at baseline (P for trend <0.001). In all age groups in both
      women and men, absolute 10-year risk of IHD and MI increased with increasing
      number of visible age-related signs. CONCLUSIONS: Male pattern baldness, earlobe
      crease, and xanthelasmata-alone or in combination-associate with increased risk
      of ischemic heart disease and myocardial infarction independent of chronological
      age and other well-known cardiovascular risk factors. This is the first
      prospective study to show that looking old for your age is a marker of poor
      cardiovascular health.

PMID- 24334177
TI  - Profile, cost and pattern of prescriptions for polymedicated patients in
      Catalonia, Spain.
AB  - OBJECTIVES: Polypharmacy is one of the main management issues in public health
      policies because of its financial impact and the increasing number of people
      involved. The polymedicated population according to their demographic and
      therapeutic profile and the cost for the public healthcare system were
      characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in
      Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered).
      PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were
      those with a consumption of >=16 drugs/month. MAIN OUTCOMES MEASURES: The study
      variables were related to age, gender and medication intake obtained from the
      2008 census and records of prescriptions dispensed in pharmacies and charged to
      the public health system. RESULTS: There were 36 880 polymedicated patients
      (women: 64.2%; average age: 74.5+/-10.9 years). The total number of prescriptions
      billed in 2008 was 2 266 830 (2 272 920 total package units). The most
      polymedicated group (up to 40% of the total prescriptions) was patients between
      75 and 84 years old. The average number of prescriptions billed monthly per
      patient was 32+/-2, with an average cost of ?452.7+/-27.5. The total cost of
      those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The
      groups N, C, A, R and M represented 71.4% of the total number of drug package
      units dispensed to polymedicated patients. Great variability was found between
      the medication profiles of men and women, and between age groups; greater
      discrepancies were found in paediatric patients (5-14 years) and the elderly
      (>=65 years). CONCLUSIONS: This study provides essential information to take
      steps towards rational drug use and a structured approach in the polymedicated
      population in primary healthcare.

PMID- 24334178
TI  - Changes in cellular degradation activity in young and old worker honeybees (Apis
      mellifera).
AB  - The trophocytes and fat cells of honeybees (Apis mellifera) have been used in
      cellular senescence studies, but the changes of cellular degradation activity
      with aging in workers are unknown. In this study, cellular degradation activity
      was evaluated in the trophocytes and fat cells of young and old workers reared in
      a field hive. The results showed the following: (1) 20S proteosome activity
      decreased with aging, whereas its expression increased with aging; (2) the
      expression of microtubule-associated protein 1 light chain 3-II (LC3-II) and the
      70 kD heat shock cognate protein (Hsc70) decreased with aging; (3) the size and
      number of autophagic vacuoles decreased with aging; (4) p62/SQSTM1 and
      polyubiquitin aggregate expression decreased with aging; (5) lysosomal efficiency
      decreased with aging; and (6) molecular target of rapamycin (mTOR) expression
      increased with aging. These results indicate that young workers have higher
      levels of cellular degradation activity than old workers and that aging results
      in a decline in the cellular degradation activity in worker honeybees.

PMID- 24334179
TI  - Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive
      individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two
      stage study.
AB  - BACKGROUND: HIV-associated diarrhea remains a significant concern with limited
      treatment options. OBJECTIVE: To determine the optimal dose, efficacy, and safety
      of crofelemer for noninfectious diarrhea. METHODS: This randomized, double-blind,
      phase 3 trial used a 2-stage design. Both stages included 2-week screening, 4
      week placebo-controlled treatment, and 20-week placebo-free (open-label)
      extension phases. In stage I, 196 HIV-seropositive patients with chronic diarrhea
      were randomized to crofelemer 125 mg, 250 mg, or 500 mg or placebo twice daily.
      Using a prospective analysis, the 125-mg twice-daily dose was selected for stage
      II. In stage II, 180 new patients were randomized to crofelemer 125 mg twice
      daily or placebo for 4 weeks. Primary efficacy analysis was the percentage of
      patients (stages I/II combined) who achieved clinical response (defined as <=2
      watery stools/week during >=2 of 4 weeks). During the placebo-free extension
      phase, response (<=2 watery stools) was assessed weekly. RESULTS: Significantly
      more patients receiving crofelemer 125 mg achieved clinical response versus
      placebo (17.6% vs 8.0%; one-sided, P = .01). Crofelemer 125 mg resulted in a
      greater change from baseline in number of daily watery bowel movements (P = .04)
      and daily stool consistency score (P = .02) versus placebo. During the placebo
      free extension phase, percentages of weekly responders ranged from 40% to 56% at
      weeks 11 to 24. Crofelemer was minimally absorbed, well tolerated, did not
      negatively impact clinical immune parameters, and had a safety profile comparable
      to placebo. CONCLUSIONS: In HIV-seropositive patients taking stable
      antiretroviral therapy, crofelemer provided significant improvement in diarrhea
      with a favorable safety profile.

PMID- 24334180
TI  - Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment
      response in HIV-1 and HCV genotype 1 coinfected persons naive to HCV therapy:
      results of the ACTG A5269 trial.
AB  - BACKGROUND: We hypothesized that nitazoxanide (NTZ) added to pegylated interferon
      alfa-2a (PEG-IFN) and weight-based ribavirin (WBR) would improve hepatitis C
      virus (HCV) virologic responses in HCV treatment-naive HIV-1/HCV genotype 1
      coinfected persons. METHODS: Prospective, single-arm study in which subjects
      received 4-week lead-in (NTZ 500 mg twice daily) followed by 48 weeks of NTZ, PEG
      IFN, and WBR. We compared the HCV virologic responses of these subjects to
      historical controls from the completed ACTG study A5178 who received PEG-IFN and
      WBR and had similar subject characteristics. Primary endpoints were early
      virologic response and complete early virologic response (EVR and cEVR). RESULTS:
      Among 67 subjects (78% male; 48% Black; median age, 50 years), EVR was achieved
      in 65.7% (90% CI, 55.0%-75.3%), cEVR in 38.8% (28.8%-49.6%). and SVR in 32.8%
      (23.4%-43.5%). EVR was higher with NTZ (51.4% in A5178; P = .03), but the
      sustained virologic response (SVR) proportion was similar (27.3% in A5178; P =
      .24). In contrast to A5178, SVR was similar across IL28B genotypes. Overall, NTZ
      was safe and well-tolerated. CONCLUSION: Whereas EVR proportion improved
      significantly in this pilot study, the addition of NTZ to PEG-IFN/WBR did not
      significantly improve SVR compared to historical controls. NTZ may be associated
      with an attenuation of the effect of IL28B on HCV treatment response.

PMID- 24334181
TI  - Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine
      during ACTG A5202.
AB  - BACKGROUND: ACTG A5202 randomized treatment-naive individuals to tenofovir
      emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz
      (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral
      load (VL) stratum (>=100,000 copies/mL) had increased rates of virologic failure
      with ABC/3TC. OBJECTIVE: To compare regimen-specific early virologic response.
      METHODS: Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes
      from entry to week 4 in A5202 subjects (N = 1,813) and from entry to week 1, 2,
      and 4 in substudy subjects (n = 179). We evaluated associations between week 4 VL
      change and time to virologic failure with Cox proportional hazards models.
      RESULTS: TDF/FTC and ABC/3TC produced similar week 4 VL declines in the entire
      study population and in the high VL stratum. EFV produced greater VL declines
      from baseline at week 4 than ATV/r (median -2.1 vs -1.9 log10 copies/mL; P <
      .001). In the substudy of subjects with week 1, 2, and 4 VL data, there was no
      difference in VL decline in individuals randomized to TDF/FTC versus ABC/3TC, but
      EFV resulted in greater VL decline from entry at each of these timepoints than
      ATV/r. Smaller week 4 VL decline was associated with increased risk of virologic
      failure. CONCLUSIONS: Within all treatment arms, a less robust week 4 virologic
      response was associated with higher risk for subsequent virologic failure.
      However, between-regimen differences in week 4 VL declines did not parallel the
      previously reported differences in longer term virologic efficacy in A5202,
      suggesting that between-regimen differences in responses were not due to
      intrinsic differences in antiviral activity.

PMID- 24334182
TI  - Genetic predictors of cervical dysplasia in African American HIV-infected women:
      ACTG DACS 268.
AB  - OBJECTIVE: To examine genome-wide associations in HIV-infected women with a
      history of cervical dysplasia compared with HIV-infected women with no history of
      abnormal Papanicolaou (Pap) tests. DESIGN: Case-control study using data from
      women analyzed for the HIV Controllers Study and enrolled in HIV treatment-naive
      studies in the AIDS Clinical Trials Group (ACTG). METHODS: Genotyping utilized
      Illumina HumanHap 650 Y or 1MDuo platforms. After quality control and principal
      component analysis, ~610,000 significant single nucleotide polymorphisms (SNPs)
      were tested for association. Threshold for significance was P < 5 * 10(-8) for
      genome-wide associations. RESULTS: No significant genomic association was
      observed between women with low-grade dysplasia and controls. The genome-wide
      association study (GWAS) analysis between women with high-grade dysplasia or
      invasive cervical cancer and normal controls identified significant SNPs. In the
      analyses limited to African American women, 11 SNPs were significantly associated
      with the development of high-grade dysplasia or cancer after correcting for
      multiple comparisons. The model using significant SNPs alone had improved
      accuracy in predicting high-grade dysplasia in African American women compared to
      the use of clinical data (area under the receiver operating characteristic curve
      for genetic and clinical model = 0.9 and 0.747, respectively). CONCLUSIONS: These
      preliminary data serve as proof of concept that there may be a genetic
      predisposition to developing high-grade cervical dysplasia in African American
      HIV-infected women. Given the small sample size, the results need to be validated
      in a separate cohort.

PMID- 24334183
TI  - Pilot study of pioglitazone and exercise training effects on basal myocardial
      substrate metabolism and left ventricular function in HIV-positive individuals
      with metabolic complications.
AB  - BACKGROUND: Individuals with HIV infection and peripheral metabolic complications
      have impaired basal myocardial insulin sensitivity that is related to left
      ventricular (LV) diastolic dysfunction. It is unknown whether interventions shown
      to be effective in improving peripheral insulin sensitivity can improve basal
      myocardial insulin sensitivity and diastolic function in people with HIV and
      peripheral metabolic complications. OBJECTIVE: In a pilot study, we evaluated
      whether the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist
      pioglitazone or combined endurance and resistance exercise training improves
      basal myocardial insulin sensitivity and diastolic function in HIV+ adults with
      peripheral metabolic complications. DESIGN: Twenty-four HIV+ adults with
      metabolic complications including peripheral insulin resistance were randomly
      assigned to 4 months of pioglitazone (PIO; 30 mg/d) or supervised, progressive
      endurance and resistance exercise training (EXS; 90-120 min/d, 3 d/wk). Basal
      myocardial substrate metabolism was quantified by radioisotope tracer methodology
      and positron emission tomography (PET) imaging, and LV function was measured by
      echocardiography. RESULTS: Twenty participants completed the study. Neither PIO
      nor EXS resulted in a detectable improvement in basal myocardial insulin
      sensitivity or diastolic function. Post hoc analyses revealed sample sizes of
      more than 100 participants are needed to detect significant effects of these
      interventions on basal myocardial insulin sensitivity and function. CONCLUSIONS:
      PIO or EXS alone did not significantly increase basal myocardial insulin
      sensitivity or LV diastolic function in HIV+ individuals with peripheral
      metabolic complications.

PMID- 24334185
TI  - Immune reconstitution inflammatory syndrome in a patient with adult-onset Still's
      disease: graft-versus-host-like skin reaction with possible asymptomatic human
      herpes virus reactivation during steroid tapering.

PMID- 24334186
TI  - Electrochemical uranyl cation biosensor with DNA oligonucleotides as receptor
      layer.
AB  - The present study aims at the further development of the uranyl oligonucleotide
      based voltammetric biosensor, which takes advantage of strong interaction between
      UO2(2+) and phosphate DNA backbone. Herein we report the optimization of working
      parameters of previously elaborated electrochemical DNA biosensor. It is shown
      that the sensor sensitivity is highly dependent on the oligonucleotide probe
      length and the incubation time of sensor in a sample solution. Consequently, the
      highest sensitivity was obtained for 10-nucleotide sequence and 60 min incubation
      time. The lower detection limit towards uranyl cation for developed biosensor was
      30 nM. The influence of mixed monolayers and the possibility of developing a non
      calibration device were also investigated. The selectivity of the proposed
      biosensor was significantly improved via elimination of adenine nucleobases from
      the DNA probe. Moreover, the regeneration procedure was elaborated and tested to
      prolong the use of the same biosensor for 4 subsequent determinations of UO2(2+).

PMID- 24334184
TI  - Lack of effect of doxycycline on trough concentrations of protease inhibitors or
      non-nucleoside reverse transcriptase inhibitors in HIV-infected patients.
AB  - BACKGROUND: Many HIV-treated patients travel to malaria-infected zones, but very
      few data are available on potential interactions between antiretroviral and
      antimalarial drugs. METHOD: We performed a pharmacokinetic study on the
      interaction of doxycycline (100 mg/d) on 2 protease inhibitors (PIs), atazanavir
      and lopinavir, and 2 non-nucleoside reverse transcriptase inhibitors (NNRTIs),
      efavirenz and nevirapine, given at usual daily doses in HIV-infected migrants
      native from sub-Saharan Africa included in the VIHVO ANRS-study before travelling
      to a sub-Saharan country. Antiretroviral trough plasma concentrations were
      measured at enrollment visit during the month preceding the travel before
      doxycycline introduction and on the week following the patients' return to France
      when they had been taking doxycycline for at least 15 days. Impact of doxycycline
      on antiretroviral concentrations was tested either with antiretroviral drugs
      separately or within the therapeutic classes (PI or NNRTI) in patients with an
      HIV RNA level <50 copies/mL at both visits and with good declared adherence. The
      Two One-Sided Test that was adapted to the Wilcoxon test was used to evidence the
      lack of interaction. Sixty-five patients receiving regimens containing atazanavir
      (n = 1), ritonavir-boosted atazanavir (n = 14), ritonavir-boosted lopinavir (n =
      23), efavirenz (n = 17), nevirapine (n = 10) were included. RESULTS: Lack of
      pharmacokinetic interaction was statistically significant when tested by
      therapeutic class (PI, P = .02; NNRTI, P = .005) and was not demonstrated for
      each antiretroviral when tested separately. CONCLUSION: This study is the first
      to assess the interaction of doxycycline on PI and NNRTI. This lack of
      pharmacokinetic interaction supports the choice of doxycycline as the
      antimalarial drug in patients treated with PI or NNRTI.

PMID- 24334187
TI  - Disclosure of authorship contributions in analgesic clinical trials and related
      publications: ACTTION systematic review and recommendations.

PMID- 24334189
TI  - 3D osteocyte lacunar morphometric properties and distributions in human femoral
      cortical bone using synchrotron radiation micro-CT images.
AB  - Osteocytes, the most numerous bone cells, are thought to be actively involved in
      the bone modeling and remodeling processes. The morphology of osteocyte is
      hypothesized to adapt according to the physiological mechanical loading. Three
      dimensional micro-CT has recently been used to study osteocyte lacunae. In this
      work, we proposed a computationally efficient and validated automated image
      analysis method to quantify the 3D shape descriptors of osteocyte lacunae and
      their distribution in human femurs. Thirteen samples were imaged using
      Synchrotron Radiation (SR) micro-CT at ID19 of the ESRF with 1.4MUm isotropic
      voxel resolution. With a field of view of about 2.9*2.9*1.4mm(3), the 3D images
      include several tens of thousands of osteocyte lacunae. We designed an automated
      quantification method to segment and extract 3D cell descriptors from osteocyte
      lacunae. An image moment-based approach was used to calculate the volume, length,
      width, height and anisotropy of each osteocyte lacuna. We employed a fast
      algorithm to further efficiently calculate the surface area, the Euler number and
      the structure model index (SMI) of each lacuna. We also introduced the 3D lacunar
      density map to directly visualize the lacunar density variation over a large
      field of view. We reported the lacunar morphometric properties and distributions
      as well as cortical bone histomorphometric indices on the 13 bone samples. The
      mean volume and surface were found to be 409.5+/-149.7MUm(3) and 336.2+/
      94.5MUm(2). The average dimensions were of 18.9+/-4.9MUm in length, 9.2+/-2.1MUm
      in width and 4.8+/-1.1MUm in depth. We found lacunar number density and six
      osteocyte lacunar descriptors, three axis lengths, two anisotropy ratios and SMI,
      that are significantly correlated to bone porosity at a same local region. The
      proposed method allowed an automatic and efficient direct 3D analysis of a large
      population of bone cells and is expected to provide reliable biological
      information for better understanding the bone quality and diseases at cellular
      level. 

PMID- 24334188
TI  - Constructing and deconstructing the gate theory of pain.
AB  - The gate theory of pain, published by Ronald Melzack and Patrick Wall in Science
      in 1965, was formulated to provide a mechanism for coding the nociceptive
      component of cutaneous sensory input. The theory dealt explicitly with the
      apparent conflict in the 1960s between the paucity of sensory neurons that
      responded selectively to intense stimuli and the well-established finding that
      stimulation of the small fibers in peripheral nerves is required for the stimulus
      to be described as painful. It incorporated recently discovered mechanisms of
      presynaptic control of synaptic transmission from large and small sensory
      afferents, which was suggested to "gate" incoming information depending on the
      balance between these inputs. Other important features included the convergence
      of small and large sensory inputs on spinal neurons that transmitted the sensory
      information to the forebrain as well as the ability of descending control
      pathways to affect the biasing established by the gate. The clarity of the model
      and its description gave this article immediate visibility, with numerous
      attempts made to test its various predictions. Although subsequent experiments
      and clinical findings have made clear that the model is not correct in detail,
      the general ideas put forth in the article and the experiments they prompted in
      both animals and patients have transformed our understanding of pain mechanisms. 

PMID- 24334190
TI  - The micro-structure of bone trabecular fracture: an inter-site study.
AB  - Trabecular bone fracture represents a major health problem, therefore the
      improvement of its assessment is mandatory for the reduction of the economic and
      social burden. The micro-structure of the trabecular bone was found to have an
      important effect on trabecular mechanical behavior. Nonetheless, the high
      variability of the trabecular micro-structure suggests a search for the local
      characteristics leading to the fracture. This work concerns the study of the
      local trabecular fracture zone and its morphometrical characterization, aiming to
      prediction of the probable fracture zone. Ninety micro-CT datasets acquired
      before and after the mechanical compression of 45 trabecular specimens were
      analyzed. Specimens were extracted from the lower limbs of two donors: 4 femora
      and 4 tibiae. A previously validated tool for the identification of the 3D
      fracture zone was applied and the local fracture zone was identified and analyzed
      in all the specimens. Fifteen morphometrical parameters were extracted for each
      local fracture zone. Standard statistical non-parametric analysis was performed
      to compare fractured and un-fractured zones together with a classification
      analysis for the prediction of the fracture zone. The statistical analysis showed
      strong statistical difference in the micro-structure of the trabecular fractured
      zone compared to the un-fractured one. Ten out of 15 measured parameters, like
      SMI, Tb.Th, BV/TV, off-axis angle, BS/BV and others, showed a statistical
      difference between full 3D fractured and un-fractured zones. Nonetheless, a
      satisfactory classification of the fractured zone was possible with none of the
      identified parameters. On the other hand, a total classification accuracy of
      95.5% was presented by the application of a linear classifier based on a
      combination of the most representative parameters, like BS/BV and the off-axis
      angle. The study points out the local essence and peculiar characteristics of the
      fracture zone, it highlights the weakness of some parameters in discriminate
      between fractured and un-fractured zones and encourage focussing the future
      studies over the local fracture zone itself with the aim to identify objective
      differences that could one day lead to the improvement of clinical assessment of
      fracture risk. 

PMID- 24334191
TI  - Simultaneous determination of Olanzapine and Fluoxetine in human plasma by LC
      MS/MS: its pharmacokinetic application.
AB  - A simple and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS)
      method has been developed and validated for the simultaneous quantitation of
      Olanzapine and Fluoxetine in human plasma using Olanzapine-d3 and Fluoxetine-d5
      HCl as internal standard (IS), respectively. After solid phase extraction of the
      plasma samples on Waters Oasis HLB Catridges, Olanzapine, Fluoxetine and IS were
      chromatographed on Thermo Hypersil Gold C18 (50 mm * 4.6 mmi.d., 5 MUm)
      analytical column with isocratic elution using methanol: 2mM Ammonium acetate
      buffer (90:10). Quantitation was performed on a triple quadrupole mass
      spectrometer employing electrospray ionization technique and operating in
      multiple reaction monitoring (MRM) and positive ion mode with transitions at
      313/256 for Olanzapine and 310/148 for Fluoxetine. The total chromatographic run
      time was 2.0 min and calibration curves were linear over the concentration range
      of 0.10-20.00 ng/mL for Olanzapine and 0.50-50.00 ng/mL for Fluoxetine. The
      method was validated for selectivity, sensitivity, recovery, linearity, accuracy
      and precision and stability studies. The recoveries obtained for the Olanzapine
      and its IS was >=87% and Fluoxetine and its IS was >=91%. Recoveries obtained
      were consistent and reproducible. Inter-batch and intra-batch coefficient of
      variation across three validation runs (LLOQ, LQC, MQC1, MQC and HQC) was less
      than 3.6 for Olanzapine and less than 5.2% for Fluoxetine. The method was
      successfully applied to a pharmacokinetic study of fixed dose combination of
      Olanzapine/Fluoxetine in healthy male volunteers.

PMID- 24334192
TI  - Superoxide dismutase isozyme detection using two-dimensional gel electrophoresis
      zymograms.
AB  - Superoxide dismutases (SODs) are ubiquitous antioxidant enzymes involved in cell
      protection from reactive oxygen species. Their antioxidant activities make them
      of interest to applied biotechnology industries and are usually sourced from
      plants. SODs are also involved in stress signaling responses in plants, and can
      be used as indicators of these responses. In this article, a suitable method for
      the separation of different SOD isoforms using two-dimensional-gel
      electrophoresis (2D-GE) zymograms is reported. The method was developed with a
      SOD standard from bovine erythrocytes and later applied to extracts from Stemona
      tuberosa. The first (non-denaturing isoelectric focusing) and second (denaturing
      sodium dodecylsulphate-polyacrylamide gel electrophoresis) dimensions of
      duplicate 2D-GE gels were stained with either Coomassie brilliant blue G-250 for
      total protein visualization, or SOD activity (zymogram) using
      riboflavin/nitroblue tetrazolium. For confirmation, putative SOD activity
      positive spots were subject to trypsin digestion and nano-liquid chromatography
      tandem mass spectrometry, followed by searching the MASCOT database for potential
      identification. The method could separate different SOD isoforms from a plant
      extract and at least partially maintain or allow renaturation to the native forms
      of the enzyme. Peptide sequencing of the 2D-GE suggested that the SODs were
      resolved correctly, identifying the control CuZn-SOD from bovine erythrocytes.
      The two SODs from S. tuberosa tubers were found to be likely homologous of a CuZn
      SOD. SOD detection and isoform separation by 2D-GE zymograms was efficient and
      reliable. The method is likely applicable to SOD detection from plants or other
      organisms. Moreover, a similar approach could be developed for detection of other
      important enzymes in the future. 

PMID- 24334193
TI  - Characterization of suspected illegal skin whitening cosmetics.
AB  - An important group of suspected illegal cosmetics consists of skin bleaching
      products, which are usually applied to the skin of the face, hands and decollete
      for local depigmentation of hyper pigmented regions or more importantly, for a
      generalized reduction of the skin tone. These cosmetic products are suspected to
      contain illegal active substances that may provoke as well local as systemic
      toxic effects, being the reason for their banning from the EU market. In that
      respect, illegal and restricted substances in cosmetics, known to have bleaching
      properties, are in particular hydroquinone, tretinoin and corticosteroids. From a
      legislative point of view, all cosmetic products containing a prohibited
      whitening agent are illegal and must be taken off the EU market. A newly
      developed screening method using ultra high performance liquid chromatography
      time off flight-mass spectrometry allows routine analysis of suspected products.
      163 suspected skin whitening cosmetics, collected by Belgian inspectors at high
      risk sites such as airports and so-called ethnic cosmetic shops, were analyzed
      and 59% were classified as illegal. The whitening agents mostly detected were
      clobetasol propionate and hydroquinone, which represent a serious health risk
      when repeatedly and abundantly applied to the skin. 

PMID- 24334194
TI  - Challenges and opportunities in the purification of recombinant tagged proteins.
AB  - The purification of recombinant proteins by affinity chromatography is one of the
      most efficient strategies due to the high recovery yields and purity achieved.
      However, this is dependent on the availability of specific affinity adsorbents
      for each particular target protein. The diversity of proteins to be purified
      augments the complexity and number of specific affinity adsorbents needed, and
      therefore generic platforms for the purification of recombinant proteins are
      appealing strategies. This justifies why genetically encoded affinity tags became
      so popular for recombinant protein purification, as these systems only require
      specific ligands for the capture of the fusion protein through a pre-defined
      affinity tag tail. There is a wide range of available affinity pairs "tag-ligand"
      combining biological or structural affinity ligands with the respective binding
      tags. This review gives a general overview of the well-established "tag-ligand"
      systems available for fusion protein purification and also explores current
      unconventional strategies under development. 

PMID- 24334195
TI  - Distribution of Po-210 in two species of predatory marine fish from the Brazilian
      coast.
AB  - Polonium-210 ((210)Po) concentration was quantified in the muscle tissue and
      organs of two predatory marine fishes (Genypterus brasiliensis and Cynoscion
      microlepidotus) from Cabo Frio, Rio de Janeiro, Brazil. The species C.
      microlepidotus, a benthic carnivore, registered higher (210)Po in its tissue. The
      organs associated with digestion displayed the maximum radionuclide compared with
      other organs. The average activity was 2 mBq kg(-1) for G. brasiliensis and it
      was 6 mBq kg(-1) for C. microlepidotus. The activity concentrations varied
      significantly between the species and among organs. 

PMID- 24334196
TI  - Xanthophyll cycle pool size and composition in several Cosmarium strains
      (Zygnematophyceae, Streptophyta) are related to their geographic distribution
      patterns.
AB  - The photosynthetic behaviour and composition of photosynthetic pigments of four
      Cosmarium strains collected from different geographic areas were examined under
      moderate and photoinhibitory white light by means of PAM fluorometry and high
      performance liquid chromatography. Generally, all of the Cosmarium strains
      displayed the photosynthetic performance and the composition of xanthophyll cycle
      pigments corresponding to that of high-light adapted plants and algae, when grown
      under the standard laboratory conditions. However, photoinhibitory treatments
      provoked several strain- and species-specific characteristics despite the long
      term cultivation in laboratory conditions. The typical arctic taxon, C. crenatum
      var. boldtianum, displayed an incomplete violaxanthin cycle yielding an
      accumulation of antheraxanthin during high light stress, which is considered as
      an adaptation to occasional high irradiances in the polar zone due to the albedo.
      So far, the violaxanthin/antheraxanthin turnover was known only in some
      prasinophycean algae. Antheraxanthin actively participated in the heat
      dissipation from PSII centres in C. crenatum, as concluded from a significant
      positive correlation between non-photochemical quenching (NPQ) and the quantity
      of antheraxanthin. In contrast, all the other Cosmarium strains displayed a
      complete violaxanthin de-epoxidase action during the high light treatments, as
      judged from the relatively high production of zeaxanthin which participated in
      thermal dissipation of excess energy. 

PMID- 24334197
TI  - Diplophrys mutabilis sp. nov., a new member of Labyrinthulomycetes from
      freshwater habitats.
AB  - Diplophrys is a ubiquitous protist genus belonging to the class
      Labyrinthulomycetes. Although most members of Labyrinthulomycetes prefer marine
      habitats, the genus Diplophrys exclusively consists of the freshwater species
      Diplophrys archeri and Diplophrys parva. To investigate the genus Diplophrys,
      several novel strains were isolated from Japanese freshwater environments, and
      cultures of the strains were established. Among the strains, an organism isolated
      from Lake Nojiri displayed some characteristic features different from that of
      both D. archeri and D. parva. Thus, we described this strain as a new species,
      Diplophrys mutabilis. D. mutabilis can be cultured using dried water flea as
      food. This species had an orbicular to fusiform shape, and it occasionally
      penetrated prey with prominent cytoplasm. From a molecular phylogenetic analysis
      based on 18S rRNA sequences, D. mutabilis evidently belongs to Amphitremida,
      Labyrinthulomycetes. This study suggests that these species form a unique group
      in Labyrinthulomycetes. 

PMID- 24334198
TI  - The Sexunzipped trial: young people's views of participating in an online
      randomized controlled trial.
AB  - BACKGROUND: Incidence of sexually transmitted infections (STIs) among young
      people in the United Kingdom is increasing. The Internet can be a suitable medium
      for delivery of sexual health information and sexual health promotion, given its
      high usage among young people, its potential for creating a sense of anonymity,
      and ease of access. Online randomized controlled trials (RCTs) are increasingly
      being used to evaluate online interventions, but while there are many advantages
      to online methodologies, they can be associated with a number of problems,
      including poor engagement with online interventions, poor trial retention, and
      concerns about the validity of data collected through self-report online. We
      conducted an online feasibility trial that tested the effects of the Sexunzipped
      website for sexual health compared to an information-only website. This study
      reports on a qualitative evaluation of the trial procedures, describing
      participants' experiences and views of the Sexunzipped online trial including
      methods of recruitment, incentives, methods of contact, and sexual health outcome
      measurement. OBJECTIVE: Our goal was to determine participants' views of the
      acceptability and validity of the online trial methodology used in the pilot RCT
      of the Sexunzipped intervention. METHODS: We used three qualitative data sources
      to assess the acceptability and validity of the online pilot RCT methodology: (1)
      individual interviews with 22 participants from the pilot RCT, (2) 133 emails
      received by the trial coordinator from trial participants, and (3) 217 free-text
      comments from the baseline and follow-up questionnaires. Interviews were audio
      recorded and transcribed verbatim. An iterative, thematic analysis of all three
      data sources was conducted to identify common themes related to the acceptability
      and feasibility of the online trial methodology. RESULTS: Interview participants
      found the trial design, including online recruitment via Facebook, online
      registration, email communication with the researchers, and online completion of
      sexual health questionnaires to be highly acceptable and preferable to
      traditional methods. Incentives might assist in recruiting those who would not
      otherwise participate. Participants generally enjoyed taking part in sexual
      health research online and found the questionnaire itself thought-provoking.
      Completing the sexual health questionnaires online encouraged honesty in
      responding that might not be achieved with other methods. The majority of
      interview participants also thought that receiving and returning a urine sample
      for chlamydia testing via post was acceptable. CONCLUSIONS: These findings
      provide strong support for the use of online research methods for sexual health
      research, emphasizing the importance of careful planning and execution of all
      trial procedures including recruitment, respondent validation, trial related
      communication, and methods to maximize follow-up. Our findings suggest that
      sexual health outcome measurement might encourage reflection on current behavior,
      sometimes leading to behavior change. TRIAL REGISTRATION: International Standard
      Randomized Controlled Trial Number (ISRCTN): 55651027; http://www.controlled
      trials.com/isrctn/pf/55651027 (Archived by WebCite at
      http://www.webcitation.org/6LbkxdPKf).

PMID- 24334199
TI  - Characteristics of urinary tract infection pathogens and their in vitro
      susceptibility to antimicrobial agents in China: data from a multicenter study.
AB  - OBJECTIVE: This study assessed the characteristics of pathogens identified in
      clinical isolates from patients with urinary tract infection (UTI) and their in
      vitro sensitivity to commonly used antibiotics in the clinical setting in China.
      DESIGN AND SETTING: Multicenter study was conducted between January and December
      2011 in 12 hospitals in China. PARTICIPANTS: Urine samples were collected from
      356 symptomatic patients treated in the study hospitals for acute uncomplicated
      cystitis, recurrent UTI or complicated UTI. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Minimal inhibitory concentrations (MICs) were measured using broth
      microdilution according to the Clinical and Laboratory Standards Institute 2011
      guidelines. Thirteen antimicrobial agents were tested: fosfomycin tromethamine,
      levofloxacin, moxifloxacin, cefdinir, cefixime, cefaclor, cefprozil, cefuroxime,
      amoxicillin/clavulanic acid, cefotaxime, azithromycin, nitrofurantoin and
      oxacillin. Escherichia coli isolates were screened and extended spectrum beta
      lactamases (ESBL) production was confirmed by a double-disk synergy test.
      RESULTS: 198 urine samples were culture-positive and 175 isolates were included
      in the final analysis. E coli was detected in 50% of cultures, followed by
      Staphylococcus epidermidis (9%), Enterococcus faecalis (9%) and Klebsiella
      pneumoniae (5%). The detection rate of ESBL-producing E coli was 53%. Resistance
      to levofloxacin was the most common among all the isolates. Nitrofurantoin and
      fosfomycin tromethamine had the greatest activity against E coli; overall, 92%
      and 91% of isolates were susceptible to these antimicrobials. E faecalis had the
      highest susceptibility rates to fosfomycin tromethamine (100%). CONCLUSIONS: The
      most frequently identified pathogens in our patients were ESBL-producing E coli
      and E faecalis. Fosfomycin tromethamine and nitrofurantoin showed a good
      antimicrobial activity against UTI pathogens. They may represent good options for
      the empiric treatment of patients with UTI.

PMID- 24334200
TI  - Acneiform eruption induced by ethosuximide.

PMID- 24334201
TI  - Planned home or hospital delivery: what outcomes provide valid comparisons?

PMID- 24334202
TI  - To the point: obstetrics and gynecology global health experiences for medical
      students.
AB  - This article, from the To the Point series prepared by the Association of
      Professors of Gynecology and Obstetrics Undergraduate Medical Education
      Committee, provides educators with an overview of considerations for obstetrics
      and gynecology global health experiences for the medical student. Options for
      integration of obstetrics and gynecology global health into undergraduate medical
      curricula are discussed. Specific considerations for global health clinical
      experiences for medical students, including choosing a clinical location,
      oversight and mentorship, goals and objectives, predeparture preparation, and
      evaluation, are reviewed. 

PMID- 24334203
TI  - The forgotten hysterectomy.

PMID- 24334204
TI  - Reply: To PMID 23791564.

PMID- 24334206
TI  - Reply: To PMID 24060444.

PMID- 24334205
TI  - Interpregnancy intervals: impact of postpartum contraceptive effectiveness and
      coverage.
AB  - OBJECTIVE: The purpose of this study was to determine the use of contraceptive
      methods, which was defined by effectiveness, length of coverage, and their
      association with short interpregnancy intervals, when controlling for provider
      type and client demographics. STUDY DESIGN: We identified a cohort of 117,644
      women from the 2008 California Birth Statistical Master file with second or
      higher order birth and at least 1 Medicaid (Family Planning, Access, Care, and
      Treatment [Family PACT] program or Medi-Cal) claim within 18 months after index
      birth. We explored the effect of contraceptive method provision on the odds of
      having an optimal interpregnancy interval and controlled for covariates. RESULTS:
      The average length of contraceptive coverage was 3.81 months (SD = 4.84). Most
      women received user-dependent hormonal contraceptives as their most effective
      contraceptive method (55%; n = 65,103 women) and one-third (33%; n = 39,090
      women) had no contraceptive claim. Women who used long-acting reversible
      contraceptive methods had 3.89 times the odds and women who used user-dependent
      hormonal methods had 1.89 times the odds of achieving an optimal birth interval
      compared with women who used barrier methods only; women with no method had 0.66
      times the odds. When user-dependent methods are considered, the odds of having an
      optimal birth interval increased for each additional month of contraceptive
      coverage by 8% (odds ratio, 1.08; 95% confidence interval, 1.08-1.09). Women who
      were seen by Family PACT or by both Family PACT and Medi-Cal providers had
      significantly higher odds of optimal birth intervals compared with women who were
      served by Medi-Cal only. CONCLUSION: To achieve optimal birth spacing and
      ultimately to improve birth outcomes, attention should be given to contraceptive
      counseling and access to contraceptive methods in the postpartum period.

PMID- 24334207
TI  - The role of NADPH oxidase in a mouse model of fetal alcohol syndrome.
AB  - OBJECTIVE: Fetal alcohol syndrome (FAS) is the most common cause of nongenetic
      mental retardation. Oxidative stress is one of the purported mechanisms.
      Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is an enzyme involved
      in the production of reactive oxygen species. Our objective was to evaluate NOX
      in the fetal brain of a well-validated mouse model of FAS. STUDY DESIGN: Timed,
      pregnant C57BL/6J mice were injected intraperitoneally with 0.03 mL/g of either
      25% ethyl alcohol or saline. Fetal brain, liver, and placenta were harvested on
      gestational day 18. The unit of analysis was the litter; tissue from 6-8 litters
      in the alcohol and control group was isolated. Evaluation of messenger
      ribonucleic acid (mRNA) expression of NOX subunits (DUOX1, DUOX2, NOX1, NOX2,
      NOX3, NOX4, NOXA1, NOXO1, RAC1, p22phox, and p67phox) was performed using
      quantitative real-time polymerase chain reaction; alcohol vs placebo groups were
      compared using a Student t test or a Mann-Whitney test (P < .05). RESULTS:
      Alcohol exposed fetal brains showed significant up-regulation in subunits DUOX2
      (1.61 +/- 0.28 vs 0.84 +/- 0.09; P = .03), NOXA1 (1.75 +/- 0.27 vs 1.09 +/- 0.06;
      P = .04), and NOXO1 (1.59 +/- 0.10 vs 1.28 +/- 0.05; P = .02). Differences in
      mRNA expression in the placenta were not significant; p67phox was significantly
      up-regulated in alcohol-exposed livers. CONCLUSION: Various NOX subunits are up
      regulated in fetal brains exposed to alcohol. This effect was not observed in the
      fetal liver or placenta. Given the available evidence, the NOX system may be
      involved in the causation of FAS through the generation of reactive oxygen
      species and may be a potential target for preventative treatment in FAS.

PMID- 24334208
TI  - Frequent relocations between asylum-seeker centres are associated with mental
      distress in asylum-seeking children: a longitudinal medical record study.
AB  - BACKGROUND: There are concerns about negative effects of relocations between
      asylum-seeker centres on the mental health of asylum-seeking children. However,
      empirical evidence comes from cross-sectional studies only. In this longitudinal
      medical record study, we aimed to assess: (i) whether relocations during the
      asylum process are associated with the incidence of newly recorded mental
      distress in asylum-seeking children; and (ii) whether this association is
      stronger among vulnerable children. METHODS: Data were extracted from the
      electronic medical records database of the Community Health Services for Asylum
      Seekers in The Netherlands (study period: 1 January 2000-31 December 2008).
      Included were 8047 children aged 4 to 17 years. Case attribution was done using
      International Classification of Primary Care codes for mental, behavioural or
      psychosocial problems. The association between annual relocation rate and
      incidence of mental distress was measured using relative risks (RR) estimated
      with multivariate Cox regression models. RESULTS: A high annual relocation rate
      (>1 relocation/year) was associated with increased incidence of mental distress
      [RR = 2.70; 95% confidence interval (CI) 2.30-3.17]. The relative risk associated
      with a high annual relocation rate was larger in children who had experienced
      violence (RR = 3.87; 95% CI 2.79-5.37) and in children whose mothers had been
      diagnosed with post-traumatic stress disorder or depression (RR = 3.40; 95% CI
      2.50-4.63). CONCLUSIONS: The risk of mental distress was greater in asylum
      seeking children who had undergone a high annual relocation rate. This risk
      increase was stronger in vulnerable children. These findings contribute to the
      appeal for policies that minimize the relocation of asylum seekers.

PMID- 24334209
TI  - Web-centred training in psychological treatments: a study of therapist
      preferences.
AB  - One barrier to the dissemination of evidence-based psychological treatments is
      the fact that few clinicians have received training in how to implement them. A
      potential solution is "web-centred training". For any training programme to be
      successful it must match the perceived needs of the trainee as otherwise there is
      likely to be poor compliance. As part of the groundwork for developing a web
      centred training program, a questionnaire on training preferences was sent to 373
      therapists who had expressed interest in the website, of whom 183 responded.
      Their top priorities were a clinically relevant website that demonstrated in
      detail how to implement the treatment. The overall characteristics and
      functioning of the website were also a major concern. There was little interest
      in being put in touch with others learning the treatment. These findings
      demonstrate the importance of surveying users' views in advance of and during the
      website development process. 

PMID- 24334210
TI  - Current evidence on treatment of patients with chronic systolic heart failure and
      renal insufficiency: practical considerations from published data.
AB  - Chronic kidney disease (CKD) is increasingly prevalent in patients with chronic
      systolic heart failure. Therefore, evidence-based therapies are more and more
      being used in patients with some degree of renal dysfunction. However, most
      pivotal randomized clinical trials specifically excluded patients with (severe)
      renal dysfunction. The benefit of these evidence-based therapies in this high
      risk patient group is largely unknown. This paper reviews data from randomized
      clinical trials in systolic heart failure and the interactions between baseline
      renal dysfunction and the effect of randomized treatment. It highlights that most
      evidence-based therapies show consistent outcome benefit in patients with
      moderate renal insufficiency (stage 3 CKD), whereas there are very scarce data on
      patients with severe (stage 4 to 5 CKD) renal insufficiency. If any, the outcome
      benefit might be even greater in stage 3 CKD compared with those with relatively
      preserved renal function. However, prescription of therapies should be
      individualized with consideration of possible harm and benefit, especially in
      those with stage 4 to 5 CKD where limited data are available. 

PMID- 24334211
TI  - Changes in endocannabinoid and N-acylethanolamine levels in rat brain structures
      following cocaine self-administration and extinction training.
AB  - Preclinical investigations have demonstrated that drugs of abuse alter the levels
      of lipid-based signalling molecules, including endocannabinoids (eCBs) and N
      acylethanolamines (NAEs), in the rodent brain. In addition, several drugs
      targeting eCBs and/or NAEs are implicated in reward and/or seeking behaviours
      related to the stimulation of dopamine systems in the brain. In our study, the
      brain levels of eCBs (anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) and
      NAEs (oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)) were analyzed via
      an LC-MS/MS method in selected brain structures of rats during cocaine self
      administration and after extinction training according to the "yoked" control
      procedure. Repeated (14days) cocaine (0.5mg/kg/infusion) self-administration and
      yoked drug delivery resulted in a significant decrease (ca. 52%) in AEA levels in
      the cerebellum, whereas levels of 2-AG increased in the frontal cortex, the
      hippocampus and the cerebellum and decreased in the hippocampus and the dorsal
      striatum. In addition, we detected increases (>150%) in the levels of OEA and PEA
      in the limbic areas in both cocaine treated groups, as well as an increase in the
      tissue levels of OEA in the dorsal striatum in only the yoked cocaine group and
      increases in the tissue levels of PEA in the dorsal striatum (both cocaine
      groups) and the nucleus accumbens (yoked cocaine group only). Compared to the
      yoked saline control group, extinction training (10days) resulted in a potent
      reduction in AEA levels in the frontal cortex, the hippocampus and the nucleus
      accumbens and in 2-AG levels in the hippocampus, the dorsal striatum and the
      cerebellum. The decreases in the limbic and subcortical areas were more apparent
      for rats that self-administered cocaine. Following extinction, there was a region
      specific change in the levels of NAEs in rats previously injected with cocaine; a
      potent increase (ca. 100%) in the levels of OEA and PEA was detected in the
      prefrontal cortex and the hippocampus, whilst a drop was noted in the striatal
      areas versus yoked saline yoked animals. Our findings support the previous
      pharmacological evidence that the eCB system and NAEs are involved in
      reinforcement and extinction of positively reinforced behaviours and that these
      lipid-derived molecules may represent promising targets for the development of
      new treatments for drug addiction. 

PMID- 24334212
TI  - GSK3beta, CREB, and BDNF in peripheral blood of patients with Alzheimer's disease
      and depression.
AB  - BACKGROUND: Glycogen synthase kinase-3beta (GSK3beta), cAMP-response element
      binding protein (CREB) and brain-derived neurotrophic factor (BDNF) play critical
      roles in neuronal survival, synaptic plasticity and memory and participate in the
      pathophysiology of both depressive disorder and Alzheimer's disease (AD).
      METHODS: This study was designed to determine the association of GSK3beta
      activity, CREB activity and BDNF concentration in peripheral blood of patients
      with AD with or without depressive symptoms and in depressive patients without
      AD. GSK3beta activity in platelets, CREB activity in lymphocytes and BDNF
      concentration in plasma, platelet-rich plasma or platelets were measured in 85 AD
      patients (36 of whom displayed co-morbid depressive symptoms), 65 non-AD patients
      with depressive disorder and 96 healthy controls. AD patients were clinically
      assessed for stage of dementia, cognitive impairment and severity of depressive
      symptoms. Depressive patients were clinically assessed for severity of
      depression. RESULTS: We observed increased CREB activity and GSK3beta activity in
      AD with depressive symptoms or in AD at mild stage of dementia. Decreased BDNF
      concentration was found in platelet-rich plasma of AD patients at moderate to
      severe stages of dementia or in AD without depressive symptoms. An association
      was revealed of the severity of cognitive impairment with the increase of
      GSK3beta in the platelets of AD patients with mild dementia. In depressive
      patients, a lower concentration of phosphorylated GSK3beta was associated with a
      higher severity of depression. Association was confirmed between severity of
      depression, CREB activation, and BDNF concentration in drug-naive depressive
      patients. CONCLUSION: Our data demonstrated that AD is accompanied by increased
      CREB activity in lymphocytes and a decreased concentration of BDNF in platelet
      rich plasma. The decreased BDNF concentration appears to correlate with moderate
      to severe stages of dementia in AD. Observation of decreased phosphorylation of
      GSK3beta in platelets of both AD patients with depressive symptoms and depressive
      patients after treatment confirms the role of increased GSK3beta activity in the
      pathophysiology of both AD and depressive disorder. Associations were confirmed
      between AD and platelet GSK3beta activity, lymphocyte CREB activity and plasma
      BDNF. CREB activity and platelet BDNF concentration seems to be related to
      depressive disorder.

PMID- 24334213
TI  - Using the GAD-Q-IV to identify generalized anxiety disorder in psychiatric
      treatment seeking and primary care medical samples.
AB  - The fourth edition of the Generalized Anxiety Disorder Questionnaire (GAD-Q-IV)
      is a self-report measure that is commonly used to screen for the presence of
      generalized anxiety disorder (GAD). The current investigation attempted to
      identify an optimal cut score using samples obtained from an outpatient
      psychiatric (n=163) and primary care clinic (n=99). Results indicated that a cut
      score of 7.67 provided an optimal balance of sensitivity (.85) and specificity
      (.74) comparable to a previously identified cut score (5.7) across both samples
      (sensitivity=.90, specificity=.66). However, both cut scores were consistently
      outperformed by a score representing the criteria for GAD described in the fourth
      edition of the Diagnostic and Statistical Manual of Mental Disorders
      (sensitivity=.89, specificity=.82). 

PMID- 24334214
TI  - Differential efficacy of cognitive-behavioral therapy and pharmacological
      treatments for pediatric obsessive-compulsive disorder: a meta-analysis.
AB  - The aim of this paper is to present a meta-analysis about the differential
      efficacy of cognitive-behavioral therapy (CBT), pharmacological and combined
      treatment for pediatric obsessive-compulsive disorder (OCD). The literature
      research and the application of the inclusion criteria enabled us to locate 18
      studies, yielding a total of 24 independent comparisons between a treated (10
      pharmacological, 11 CBT, and 3 combined interventions) and a control group. All
      types of interventions were efficacious in reducing obsessive-compulsive
      symptoms, with effect sizes adjusted by the type of control group of d=1.203 for
      CBT, d=0.745 for pharmacological treatments, and d=1.704 for mixed treatments.
      Depression, anxiety and other secondary responses were also improved, especially
      with CBT interventions. The analysis of moderator variables showed that the CBT
      protocol and the total of intervention hours exhibited a significant influence on
      the effect size. Within pharmacological treatment, clomipramine (d=1.305) was
      more efficacious than selective serotonin reuptake inhibitors (d=0.644), but its
      adverse effects were more severe. Finally, the clinical implications of the
      results are discussed. 

PMID- 24334215
TI  - The intrinsic dynamics of Cse1p and Xpot elucidated by coarse-grained models.
AB  - Cse1p and Xpot are two karyopherin proteins that transport the corresponding
      cargos during the nucleocytoplasmic transport. We utilized Elastic Network Model
      (ENM) and Finite Element Analysis (FEA) to study their conformational dynamics.
      These dynamics were interpreted by their intrinsic modes that played key roles in
      the flexibility of karyopherins, which further affected the binding affinities.
      The findings included that it was the karyopherin's versatile conformations
      composed of the same superhelices of HEAT repeats that produced different degrees
      of functional flexibilities. We presented evidence that these coarse-grained
      methods could help to elucidate the biological function behind the structures of
      the two karyopherins. 

PMID- 24334217
TI  - alpha4beta7 integrin: beyond T cell trafficking.

PMID- 24334216
TI  - The Sexunzipped trial: optimizing the design of online randomized controlled
      trials.
AB  - BACKGROUND: Sexual health problems such as unwanted pregnancy and sexually
      transmitted infection are important public health concerns and there is huge
      potential for health promotion using digital interventions. Evaluations of
      digital interventions are increasingly conducted online. Trial administration and
      data collection online offers many advantages, but concerns remain over
      fraudulent registration to obtain compensation, the quality of self-reported
      data, and high attrition. OBJECTIVE: This study addresses the feasibility of
      several dimensions of online trial design-recruitment, online consent,
      participant identity verification, randomization and concealment of allocation,
      online data collection, data quality, and retention at 3-month follow-up.
      METHODS: Young people aged 16 to 20 years and resident in the United Kingdom were
      recruited to the "Sexunzipped" online trial between November 2010 and March 2011
      (n=2036). Participants filled in baseline demographic and sexual health
      questionnaires online and were randomized to the Sexunzipped interactive
      intervention website or to an information-only control website. Participants were
      also randomly allocated to a postal request (or no request) for a urine sample
      for genital chlamydia testing and receipt of a lower (L10/US$16) or higher
      (L20/US$32) value shopping voucher compensation for 3-month outcome data.
      RESULTS: The majority of the 2006 valid participants (90.98%, 1825/2006) were
      aged between 18 and 20 years at enrolment, from all four countries in the United
      Kingdom. Most were white (89.98%, 1805/2006), most were in school or training
      (77.48%, 1545/1994), and 62.81% (1260/2006) of the sample were female. In total,
      3.88% (79/2036) of registrations appeared to be invalid and another 4.00%
      (81/2006) of participants gave inconsistent responses within the questionnaire.
      The higher value compensation (L20/US$32) increased response rates by 6-10%,
      boosting retention at 3 months to 77.2% (166/215) for submission of online self
      reported sexual health outcomes and 47.4% (118/249) for return of chlamydia urine
      samples by post. CONCLUSIONS: It was quick and efficient to recruit young people
      to this online trial. Our procedures for obtaining online consent, verifying
      participant identity, automated randomization, and concealment of allocation
      worked well. The optimal response rate for the online sexual health outcome
      measurement was comparable to face-to-face trials. Multiple methods of
      participant contact, requesting online data only, and higher value compensation
      increased trial retention at 3-month follow-up. TRIAL REGISTRATION: International
      Standard Randomized Controlled Trial Number (ISRCTN): 55651027;
      http://www.controlled-trials.com/ISRCTN55651027 (Archived by WebCite at
      http://www.webcitation.org/6LbkxdPKf).

PMID- 24334218
TI  - Alopecia areata developing during ustekinumab therapy: report of two cases.

PMID- 24334220
TI  - Structure elucidation of capsular polysaccharides from Streptococcus pneumoniae
      serotype 33C, 33D, and revised structure of serotype 33B.
AB  - We report herein the previously unknown structures of the pneumococcal capsular
      polysaccharides serotype 33C and 33D, and a revised structure of serotype 33B.
      The syntenic pair 33B/33D has nearly identical polysaccharide repeat units with
      the exception of one sugar residue (->2-alpha-Glcp in 33B and ->2-alpha-Galp in
      33D). Serotype 33C is structurally more similar to 33B/33D than 33A/33F, in that
      it also possesses a backbone ribitol-phosphate group and a ->3-beta-GalpNAc
      residue, both of which are absent in the repeat units of 33A/33F. Serotype 33C is
      notably different from all other serogroup 33 polysaccharides, as there is no ->3
      beta-Glcp residue and the location of the O-acetylation of the ->5-beta-Galf
      residue (O-6) differs from the other serogroup 33 polysaccharides (O-2). This
      completes the structural assignments of polysaccharides within serogroup 33 and
      provides a framework for understanding the recognition of epitopes by serogroup
      33 typing sera based on observed cross-reactivities reported in the literature. 

PMID- 24334219
TI  - A novel alkyne cholesterol to trace cellular cholesterol metabolism and
      localization.
AB  - Cholesterol is an important lipid of mammalian cells and plays a fundamental role
      in many biological processes. Its concentration in the various cellular membranes
      differs and is tightly regulated. Here, we present a novel alkyne cholesterol
      analog suitable for tracing both cholesterol metabolism and localization. This
      probe can be detected by click chemistry employing various reporter azides.
      Alkyne cholesterol is accepted by cellular enzymes from different biological
      species (Brevibacterium, yeast, rat, human) and these enzymes include cholesterol
      oxidases, hydroxylases, and acyl transferases that generate the expected
      metabolites in in vitro and in vivo assays. Using fluorescence microscopy, we
      studied the distribution of cholesterol at subcellular resolution, detecting the
      lipid in the Golgi and at the plasma membrane, but also in the endoplasmic
      reticulum and mitochondria. In summary, alkyne cholesterol represents a
      versatile, sensitive, and easy-to-use tool for tracking cellular cholesterol
      metabolism and localization as it allows for manifold detection methods including
      mass spectrometry, thin-layer chromatography/fluorography, and fluorescence
      microscopy. 

PMID- 24334221
TI  - Perceptibility and acceptability thresholds for colour differences in dentistry.
AB  - INTRODUCTION: Data on acceptability (AT) and perceptibility thresholds (PT) for
      colour differences vary in dental literature. There is consensus that the
      determination of DeltaE* is appropriate to define AT and PT, however there is no
      consensus regarding the values that should be used. The aim of this clinical
      review was to provide a systematic approach to the topic of colour science of
      high clinical relevance to dental research. MATERIALS AND METHODS:
      MEDLINE/PubMed, WoS and EBSCO databases were searched up to January 7, 2013; the
      outcome was restricted to English, and to clinical studies were
      spectrophotometers were used for measurement. RESULTS: Forty-eight studies were
      eligible and met the inclusion criteria. Of the 48 studies there appeared to be a
      trend in their source references: 44% referred to the same study for the PT
      (DeltaE*=1); and 35% referred to the same article for the AT (DeltaE*=3.7).
      CONCLUSIONS: More than half the studies defined PT as DeltaE*=1, and one third of
      the studies referred to DeltaE*=3.7 as the threshold at which 50% of observers
      accepted the colour difference. Most clinical studies refer to the same few in
      vitro literature that have attempted to determine PT and AT from decades ago.

PMID- 24334222
TI  - Gypenosides pre-treatment protects the brain against cerebral ischemia and
      increases neural stem cells/progenitors in the subventricular zone.
AB  - Gypenosides (GPs) have been reported to have neuroprotective effects in addition
      to other bioactivities. The protective activity of GPs during stroke and their
      effects on neural stem cells (NSCs) in the ischemic brain have not been fully
      elucidated. Here, we test the effects of GPs during stroke and on the NSCs within
      the subventricular zone (SVZ) of middle cerebral artery occlusion (MCAO) rats.
      Our results show that pre-treatment with GPs can reduce infarct volume and
      improve motor function following MCAO. Pre-treatment with GPs significantly
      increased the number of BrdU-positive cells in the ipsilateral and contralateral
      SVZ of MCAO rats. The proliferating cells in both sides of the SVZ were glial
      fibrillary acidic protein (GFAP)/nestin-positive type B cells and doublecortin
      (DCX)/nestin-positive type A cells. Our data indicate that GPs have
      neuroprotective effects during stroke which might be mediated through the
      enhancement of neurogenesis within the SVZ. These findings provide new evidence
      for a potential therapy involving GPs for the treatment of stroke. 

PMID- 24334223
TI  - Synthesis of a novel molecularly imprinted organic-inorganic hybrid polymer for
      the selective isolation and determination of fluoroquinolones in tilapia.
AB  - A novel molecularly imprinted organic-inorganic hybrid polymer (MI-MAA/APTS)
      based on a dummy molecular imprinting technique and an organic-inorganic hybrid
      material technique was synthesised and used as a sorbent in solid-phase
      extraction for the selective isolation and determination of ofloxacin (OFL),
      lomefloxacin (LOM), and ciprofloxacin (CIP) in tilapia samples. The MI-MAA/APTS
      sorbent was prepared from 3-aminopropyltriethoxysilanes (APTS) as an inorganic
      source and methacrylic acid (MAA) as an organic source and exhibited high
      mechanical strength and special affinities to the analytes. A comparison of MI
      MAA/APTS with other conventional sorbents (C18 and HLB) showed that MI-MAA/APTS
      displayed good selectivity and affinity for OFL, LOM, and CIP, and the recoveries
      of the analytes at three spiked levels were in the range of 85.1-101.0%, with the
      relative standard deviations <=5.1%. The presented MI-MAA/APTS-SPE-HPLC method
      could be potentially applied to the determination of fluoroquinolones (FQs) in
      complex fish samples. 

PMID- 24334224
TI  - O-linked glycosylation analysis of recombinant human granulocyte colony
      stimulating factor produced in glycoengineered Pichia pastoris by liquid
      chromatography and mass spectrometry.
AB  - Glycosylation is a major biochemical attribute of therapeutic proteins and
      detailed analyses including the structures and sites of such modifications are
      often required for product quality control and assurance. Using liquid
      chromatography and tandem mass spectrometry techniques, we analyzed the O-linked
      glycosylation of recombinant human granulocyte colony-stimulating factor (rhG
      CSF) derived from glycoengineered Pichia pastoris with regard to its nature,
      structure, occupancy, and location. Peptide mappings using protease and chemical
      cleavages were performed to determine the specific O-linked glycosylation site
      used by Pichia-derived rhG-CSF. Our results demonstrated that Thr134, the
      equivalent O-linked glycosylation site found on endogenous human G-CSF, is the
      only site modified with a single mannose, allowing glycoengineered P. pastoris to
      be used as a viable production platform for therapeutic rhG-CSF. 

PMID- 24334225
TI  - A quantitative LC-MS/MS method for determination of thiazolidinedione mitoNEET
      ligand NL-1 in mouse serum suitable for pharmacokinetic studies.
AB  - Thiazolidinedione (TZD) compounds have shown promise as antidiabetic,
      antibiotics, antifungal and neuroprotective agents. The mitochondrial effect of a
      novel mitoNEET ligand, NL-1 {5-[(3,5-di-tert-butyl-4-hydroxyphenyl)methyl]-1,3
      thiazolidine-2,4-dione}, and other TZD compounds, is a newly proposed mechanism
      for the neuroprotective action of these TZD compounds. In this work, a sensitive
      LC-MS/MS assay has been developed and validated for quantification of NL-1 in
      mouse serum. Sample preparation involved an acetonitrile protein precipitation
      procedure with addition of an internal standard NL-2 {5-[(4-hydroxy-3,5-dimethyl
      phenyl)methyl]thiazolidine-2,4-dione}. LC-MS/MS analysis utilized a Columbus C-18
      HPLC column (2mm*50mm, 5MUm). Chromatography employed a multiple step gradient
      program that featured a steep linear gradient (25-95% in 0.5min) of 15MUM
      ammonium acetate (additive for eliminating carry-over) in 2% methanol mixing with
      increasing proportions of 100% methanol. The HPLC was interfaced to a QTrap 5500
      mass spectrometer (AB Sciex) equipped with an electrospray ionization source used
      in a negative ionization mode. Multiple reaction monitoring (MRM) of m/z 334->263
      for NL-1 and m/z 250->179 for NL-2 was done. The method had a linear range of at
      least 1-100ng/mL in serum. The intra-assay and inter-assay percent coefficient of
      variation (%CV) were less than 4% and accuracies (%RE) ranged from -2.7% to 2.0%.
      The analytical procedure gave 96-115% absolute extraction recovery of NL-1. The
      relative matrix effect was measured and found to be insignificant. The analyte in
      serum was confirmed to be stable during storage and treatment. The method is
      suitable for pharmacokinetic (PK) studies of the parent drug NL-1 based on the
      preliminary serum results from dosed NL-1 mouse studies. 

PMID- 24334226
TI  - Language profiles in children with Down syndrome and children with language
      impairment: implications for early intervention.
AB  - This study investigated early language profiles in two groups of children with
      developmental disability: children with Down Syndrome (DS, n=13) and children
      with Language Impairment (LI, n=16). Vocabulary and grammatical skills in the two
      groups were assessed and compared to language skills of typically developing (TD)
      children matched on size of either their receptive or expressive vocabulary
      (n=58). The study aimed to establish if language development in these groups is
      delayed or fundamentally different than the TD groups, and if the group with DS
      showed a similar language profile to the group with LI. There is a clinical
      motivation to identify possible key risk characteristics that may distinguish
      children who are likely to have LI from the variation observed in TD children.
      Three clear findings emerged from the data. Firstly, both receptive and
      expressive vocabulary compositions did not significantly differ in the clinical
      groups (DS and LI) after being matched to the vocabulary size of TD children.
      This provides further support for the idea that word learning for the children in
      the clinical groups is delayed rather than deviant. Secondly, children with LI
      showed a significantly larger gap between expressive and receptive word
      knowledge, but children with DS showed a pattern comparable to TD children.
      Thirdly, children with LI who understood a similar number of words as the TD
      children still had significantly poorer grammatical skills, further underlining
      the dissociation between lexical and grammatical skills in children with LI.
      Grammatical skills of children with DS were commensurate with their lexical
      skills. The findings suggest that language intervention should be specifically
      tailored to etiology rather than focused on general communication strategies,
      particularly in children with LI. 

PMID- 24334227
TI  - An examination of Anglo and Latino parenting practices: relation to behavior
      problems in children with or without developmental delay.
AB  - The transactional model of development has received empirical support in research
      on at-risk children. However, little is known about the role of ethnicity or
      child delay status (i.e., developmental delay [DD] or typical cognitive
      development [TD]) in the process of parents adapting to their child's behavior
      problems and special needs. We examined whether Latina (N=44) and Anglo (N=147)
      mothers of 3-year-old children with or without DD differed in their use of two
      parenting practices, maternal scaffolding and sensitivity. We also examined how
      the status and ethnic groups differed in child behavior problems at ages 3 and 5
      and whether parenting predicted change in behavior problems over time in the
      ethnic and status groups. Analyses generally supported previous research on
      status group differences in behavior problems (DD higher) and parenting practices
      (TD higher). Parenting practices predicted a decrease in externalizing problems
      from child age 3 to 5 years among Latino families only. Child developmental
      status was not associated with change in behavior problems. Cultural perspectives
      on the transactional model of development and implications for intervention are
      discussed. 

PMID- 24334228
TI  - Motion analysis of throwing Boccia balls in children with cerebral palsy.
AB  - Boccia is a sport suitable for children with cerebral palsy (CP). Throwing Boccia
      balls requires upper extremity and torso coordination. This study investigated
      the differences between children with CP and normally developed children
      regarding throwing patterns of Boccia balls. Thirteen children with bilateral
      spastic CP and 20 normally developed children participated in this study. The
      tests in this study were a pediatric reach test and throwing of Boccia balls. A
      3D electromagnetic motion tracking system and a force plate were synchronized to
      record and analyze biomechanical parameters of throwing Boccia balls. The results
      of the pediatric reach test for participants with CP were significantly worse
      than those for normally developed participants. The 2 groups of participants did
      not significantly differ regarding the distance between a thrown Boccia ball and
      a target ball (jack). Participants with CP demonstrated significantly longer
      movement duration, smaller amplitude of elbow movement, greater amplitudes of
      shoulder abduction and flexion, slower maximal velocity of torso flexion and the
      linear velocity of moving the wrist joint forward, faster maximal velocity of
      head flexion, and smaller sway ratio compared with normally developed
      participants when throwing Boccia balls. Participants with CP seemed to mainly
      use head and shoulder movements to bring the Boccia balls forward with limited
      torso movement. Normally developed participants brought the Boccia ball forward
      with faster torso and greater elbow movement while stabilizing head and shoulder
      movements. Nevertheless, participants with CP did not demonstrate significantly
      worse performance in the throwing accuracy of Boccia balls. 

PMID- 24334229
TI  - Toddlers with delayed expressive language: an overview of the characteristics,
      risk factors and language outcomes.
AB  - "Late talkers" is a term used in the scientific field of atypical language
      development to describe toddlers who exhibit delay in expressive language skills,
      although they do have intact receptive skills. This article provides an overview
      of the literature on late talking toddlers. Specifically, it underscores the risk
      factors for late talking as well as the parenting and individual characteristics
      of this group of children. It also presents the association between expressive
      language delay and the behavioral and socio-emotional development of late
      talkers, and the language outcomes of late talking toddlers at a later point in
      development. Our review culminates with recommendations and intervention
      guidelines for clinicians. 

PMID- 24334230
TI  - Use of behavioral change techniques in web-based self-management programs for
      type 2 diabetes patients: systematic review.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic
      metabolic disease characterized by hyperglycemia and cardiovascular risks.
      Without proper treatment, T2DM can lead to long-term complications. Diabetes self
      management is recognized as the cornerstone of overall diabetes management. Web
      based self-management programs for T2DM patients can help to successfully improve
      patient health behaviors and health-related outcomes. Theories can help to
      specify key determinants of the target behaviors and behavior change strategies
      required to arrive at the desired health outcomes, which can then be translated
      into specific behavioral techniques or strategies that patients can learn to
      apply in their daily life. From previous reviews of a wide range of online
      diabetes self-management tools and programs, it appears that it is still unclear
      which behavioral change techniques (BCTs) are primarily used and are most
      effective when it comes to improving diabetes self-management behaviors and
      related health outcomes. OBJECTIVE: We set out to identify which BCTs are being
      applied in online self-management programs for T2DM and whether there is
      indication of their effectiveness in relation to predefined health outcomes.
      METHODS: Articles were systematically searched and screened on the mentioned use
      of 40 BCTs, which were then linked to reported statistically significant
      improvements in study outcomes. RESULTS: We found 13 randomized controlled trials
      reporting on 8 online self-management interventions for T2DM. The BCTs used were
      feedback on performance, providing information on consequences of behavior,
      barrier identification/problem solving, and self-monitoring of behavior. These
      BCTs were also linked to positive outcomes for health behavior change,
      psychological well-being, or clinical parameters. CONCLUSIONS: A relatively small
      number of theory-based online self-management support programs for T2DM have been
      reported using only a select number of BCTs. The development of future online
      self-management interventions should be based on the use of theories and BCTs and
      should be reported accurately.

PMID- 24334231
TI  - An outbreak of hand-foot-and-mouth disease mimicking chicken pox, with a frequent
      association of onychomadesis in Japan in 2009: a new phenotype caused by
      coxsackievirus A6.

PMID- 24334232
TI  - Is culture associated with patient safety in the emergency department? A study of
      staff perspectives.
AB  - OBJECTIVE: To describe the patient safety culture of Dutch emergency departments
      (EDs), to examine associations between safety culture dimensions and patient
      safety grades as reported by ED staff and to compare these associations between
      nurses and physicians. DESIGN: Cross-sectional survey conducted in 2007. SETTING:
      Thirty-three non-academic EDs in the Netherlands. PARTICIPANTS: Four hundred and
      eighty nurses, 159 physicians and 91 other professionals. MAIN OUTCOME MEASURE:
      Self-reported level of patient safety. RESULTS: In unadjusted analyses, all
      dimensions of safety culture were positively associated with the reported level
      of patient safety and six of these associations with patient safety were
      statistically significant after adjustment ('teamwork across units', 'frequency
      of event reporting', communication openness', 'feedback about and learning from
      errors', 'hospital management support for patient safety'). Differences between
      nurses and physicians were found on two dimensions ('frequency of event
      reporting' and ' hospital management support for patient safety'). Physicians
      tended to grade patient safety higher than nurses whilst having equal judgements
      on these two dimensions. CONCLUSIONS: Staff identified several dimensions of
      safety culture that are associated with staff-reported safety in the ED.
      Physicians and nurses identified distinct dimensions of safety culture as
      associated with reported level of patient safety.

PMID- 24334233
TI  - Patient-reported experiences with hospitals: comparison of proxy and patient
      scores using propensity-score matching.
AB  - OBJECTIVE: The objective of this study was to compare patient-experience scores
      between patients with a proxy response and without a proxy response, using
      propensity-score matching to maximize the comparability between these two groups.
      DESIGN: Cross-sectional survey. SETTING: Hospital inpatient services in Norway.
      PARTICIPANTS: Patients were randomly selected from each of the 61 hospitals in
      Norway during spring 2011. Postal questionnaires were mailed to 23 420 patients
      after their discharge from hospital. INTERVENTION: No intervention. MAIN OUTCOME
      MEASURES: All of the patient respondents (n = 8744) and the matched cases (n =
      734) were compared with patients with a proxy response (n = 734) on 12 patient
      experience indicators using t-tests. RESULTS: Compared with patient respondents,
      patients with a proxy response had poorer health, were older and were more often
      discharged from the hospital to another health-care institution (P < 0.001).
      Patients with a proxy response yielded significantly lower patient-experience
      scores than those without a proxy response for 9 of the 12 indicators. Compared
      with the matched patient group, patients with a proxy response had significantly
      lower scores for 3 of the 12 indicators and a significantly higher score for one
      indicator. Differences in scores between patients with a proxy response and the
      matched patient sample were small, with the largest difference being 4 on a scale
      of 0-100. CONCLUSIONS: Patients with a proxy response report somewhat poorer
      experiences than those without a proxy response; however, proxies represent a
      different patient group than the patient group as a whole, and the results were
      very similar after controlling for these differences.

PMID- 24334234
TI  - ortho-Methylphenylthioglycosides as glycosyl building blocks for preactivation
      based oligosaccharide synthesis.
AB  - Thioglycosides are widely used in orthogonal glycosylation, armed-disarmed
      chemoselective glycosylation, and preactivation-based glycosylation.
      Nevertheless, aglycon transfer occasionally occurred in the glycosylation process
      of thioglycosides. This problem was also encountered in preactivation-based
      reactions, which limited the applications of preactivation-based glycosylation to
      some extent. To tackle this problem, sterically hindered aglycon ortho
      methylphenylthioglycosides were introduced as glycosyl building blocks. These
      thioglycosides prevented the aglycon transfer and enhanced the efficiency of
      glycosyl coupling reactions, especially in the reactions of disarmed donors with
      armed acceptors. Moreover, these thioglycosides were employed in preactivation
      based one-pot oligosaccharide assembly. 

PMID- 24334235
TI  - Pyrrolidine-type iminosugars from leaves of Suregada glomerulata.
AB  - Phytochemical investigation of the H2O extract of leaves of Suregada glomerulata
      led to the isolation of ten pyrrolidine-type iminosugars. The chemical structures
      of the six new compounds (4-6, 8-10) were elucidated as 2,5-imino-2,4,5-trideoxy
      d-manno-heptitol (4-deoxy-homoDMDP) (4), 2,5-imino-2,4,5-trideoxy-d-gulo-heptitol
      (5), 2,5-imino-2,4,5,6-tetradeoxy-d-gulo-heptitol (6), 6-C-butyl-4-deoxy-DMDP
      (8), 6-C-(8-hydroxyoctyl)-DMDP (9), and 6-C-(8-hydroxyoctyl)-2,5-dideoxy-2,5
      imino-d-galactitol (10), respectively, on the basis of spectroscopic data
      analysis (NMR and HRESIMS). Compounds 4-6 and 8 were characterized as rarely seen
      4-deoxy pyrrolidine-type iminosugars. Pyrrolidine-type iminosugars with a long
      side chain have been found in the restrictive plant families Moraceae,
      Campanulaceae, and Hyacinthaceae. The discovery of compounds 9 and 10 with a C8
      side chain from S. glomerulata (Euphorbiaceae) expands the range of distribution
      for the iminosugars in plants. The 8-hydroxyoctyl side-chain represents a new
      addition for the molecular diversity of iminosugars. The compounds 1-10 were
      evaluated for inhibitory activity against rat intestinal alpha-glucosidase.
      However, all the test compounds showed no significant inhibitory activities to
      the glucosidase. 

PMID- 24334236
TI  - The interaction of enoxaparin and fondaparinux with calcium.
AB  - The main sites of calcium binding were determined for the low molecular weight
      heparin drug enoxaparin and the synthetic pentasaccharide Arixtra (fondaparinux).
      [(1)H,(13)C] HSQC pH titrations were carried out to characterize the acid-base
      properties of these samples both in the presence and absence of calcium. The
      differences in the titration curves were used to determine the structural
      components of enoxaparin and fondaparinux responsible for Ca(2+) binding. In
      enoxaparin both unsubstituted and 2-O-sulfated iduronic acid residues are
      important in calcium binding and the presence of the 2-O-sulfo group does not
      seem to influence the Ca(2+) binding capability of the iduronate ring. In
      fondaparinux changes in chemical shifts upon Ca(2+) binding were smaller than
      observed for enoxaparin, and were observed for both the glucuronic acid and 2-O
      sulfated iduronic acid residues. In enoxaparin significant perturbations of the
      chemical shift of the N-sulfoglucosamine anomeric carbon in residues connected to
      2-O-sulfated iduronic acid were detected on Ca(2+) binding, however it was not
      possible to determine whether these changes reflect direct involvement in calcium
      complexation or result from through space interactions or conformational changes.

PMID- 24334237
TI  - Regulating effect of tea polyphenols on endothelin, intracellular calcium
      concentration, and mitochondrial membrane potential in vascular endothelial cells
      injured by Angiotensin II.
AB  - BACKGROUND: Polyphenols are the main active component of tea and are considered
      an antiatherosclerosis agent, protecting vascular endothelial cells (VECs) from
      injury and preventing cardiovascular diseases. Endothelin level, intracellular
      calcium concentration, and mitochondrial membrane potential in VECs directly
      reflect the function and injury status of cells. The objective of this study was
      to study the regulating effects of tea polyphenols on these factors in VECs
      injured by angiotensin II (Ang-II) and explore the protective effect of tea
      polyphenols on human VECs. METHODS: In this study, human aortic vascular
      endothelial cells were divided into 4 groups: (1) a control group; (2) Ang-II
      group: Ang-II at a concentration of 10(-7) mol/L was added to the cells; (3) low
      concentration tea polyphenols + Ang-II group: tea polyphenols at a concentration
      of 5 mg/L was added in addition to Ang-II; (4) high-concentration tea polyphenols
      + Ang-II group: tea polyphenols at a concentration of 25 mg/L was added in
      addition to Ang-II. One hundred microliters of supernatant was extracted before
      treatment and at 0.5, 6, and 24 hours after treatment in each group to establish
      the content of endothelin. RESULTS: The results showed the following: (1) tea
      polyphenols decreased the expression of endothelin-1 messenger RNA, which was
      increased by Ang-II (P < 0.01). (2) Tea polyphenols inhibited endothelin
      secretion induced by Ang-II (P < 0.01), and the inhibition of low-concentration
      tea polyphenols was superior to that of high concentration tea polyphenols (P <
      0.01). (3) Tea polyphenols ameliorated the changes in intracellular calcium
      concentration and mitochondrial membrane potential induced by Ang-II (P < 0.01).
      CONCLUSIONS: This study suggests that tea polyphenols may effectively protect
      VECs against injury by regulating endothelin, intracellular calcium
      concentration, and mitochondrial membrane potential in VECs injured by Ang-II.
      Additionally, lower dose would be used clinically rather than the higher dose for
      obtaining better results.

PMID- 24334238
TI  - To shunt or not to shunt? An experimental study comparing temporary vascular
      shunts and venous ligation as damage control techniques for vascular trauma.
AB  - BACKGROUND: To evaluate vascular flow through temporary vascular shunts inserted
      into peripheral arteries and veins and the repercussion, on the arterial
      perfusion, of venous ligation and venous shunt insertion in an experimental model
      for damage control. METHODS: Experimental study in pigs. Animals were distributed
      in 5 groups: group 1, right external iliac artery (EIA) shunting and right
      external iliac vein (EIV) ligation; group 2, right EIA shunting and right EIV
      shunting; group 3, right EIV ligation; group 4, right EIV shunting; group 5, no
      vascular shunting and no venous ligation. Flowmeters were used to measure
      vascular flow on right and left external iliac vessels, and blood samples were
      collected from the EIVs for biochemical analysis. A right anterior limb biopsy
      was performed before shock. Hemorrhagic shock was induced through the external
      right jugular vein, until the vascular flow through right iliac external artery
      shunt or right iliac external vein shunt (group 4) ceased or until the animal's
      death. After the end of the experiments, biopsies of bilateral hind limb were
      obtained for histologic analysis. For statistical analysis, Microsoft Office
      Excel 2007 and BioEstat 5.0 (2007) were used. RESULTS: In the absence of
      hemorrhagic shock, venous ligation (group 1) was associated with a 38.8%
      reduction (P < 0.05) and venous shunting with a 28.4% reduction on the vascular
      flow through the arterial shunt. When associated with hemorrhagic shock, the mean
      vascular flow on the right EIA was 13 mL/min and on the left EIA was 41.2 mL/min;
      on group 2, the right EIA flow was 8.5 mL/min and the left EIA flow was 8.1
      mL/min. When associated with hemorrhagic shock, the pO2 was 25.8 mm Hg on right
      EIV and 33.8 mm Hg on the left EIV for group 1 (P < 0.05), whereas for group 2,
      the pO2 was 22.6 mm Hg on right EIV and 22.8 mm Hg on the left EIV. On group 1,
      serum potassium was 3.84 mEq/L on the right EIV and 3.96 mEq/L on the left EIV,
      whereas on group 2, it was 7.1 mEq/L on the right EIV and 5.88 mEq/L on the left
      EIV (P < 0.05). CONCLUSIONS: In the developed experimental model, venous
      shunting, when compared with venous ligation, offered less resistance to vascular
      flow through the arterial shunt and allowed a more efficient limb venous drainage
      than simple vein ligature.

PMID- 24334239
TI  - End-to-end renal vein anastomosis to preserve renal venous drainage following
      inferior vena cava radical resection due to leiomyosarcoma.
AB  - BACKGROUND: When retrohepatic inferior vena cava (IVC) resection is required, for
      example, for IVC leiomyosarcoma, reconstruction is recommended. This is
      particularly true when the renal vein confluence is resected to preserve venous
      outflow, including that of the right kidney. METHODS: Two patients with
      retrohepatic IVC leiomyosarcoma involving renal vein confluences underwent
      hepatectomy with en bloc IVC resection below the renal vein confluence. IVC
      reconstruction was not performed, but end-to-end renal vein anastomoses were,
      including a prosthetic graft in 1 case. RESULTS: The postoperative course was
      uneventful with respect to kidney function, anastomosis patency assessed using
      Doppler ultrasonography and computerized tomography, and transient lower limb
      edema. DISCUSSION: End-to-end renal vein anastomosis after a retrohepatic IVC
      resection including the renal vein confluence should be considered as an
      alternative option for preserving right kidney drainage through the left renal
      vein when IVC reconstruction is not possible or should be avoided.

PMID- 24334240
TI  - Rifampin soaking dacron-based endografts for implantation in infected aortic
      aneurysms--new application of a time-tested principle.
AB  - Infections involving the aorta are associated with high rates of morbidity and
      mortality, and their management is complex. Saturating Dacron grafts in rifampin
      (60 mg/mL) inhibits the growth of organisms commonly found to be involved in both
      primary aortic infections and aortoenteric fistulas. Open repair and replacement
      of the aorta with rifampin-soaked Dacron grafts is frequently used in clinical
      practice and is considered a viable option for open repair with a low recurrence
      of infection; however, the morbidity and mortality of the procedure is
      significant. More recently, patients who are high risk for open surgery have been
      managed with endografts to treat infected aortas and aortoenteric fistulas with
      limited success, a high recurrence rate, and elevated mortality. We describe a
      technique to expose Dacron endografts with rifampin delivered via injection port
      or into the sheath before deployment in selected patients with aortic infections.
      We used this novel technique in 2 patients who were high risk for open repair: 1
      with a bleeding aortoenteric fistula and 1 with mycotic abdominal aortic
      aneurysm. The first patient tolerated 1.5 years without surgical correction of
      the duodenal defect after placement of a rifampin-treated endograft. This allowed
      her to recover and ultimately undergo definitive repair under elective
      circumstances. Our second patient remains without evidence of recurrence 1 year
      after implantation for a mycotic abdominal aortic aneurysm. Following the
      principles of rifampin use in open vascular repairs, treating Dacron endografts
      with rifampin may add similar antimicrobial resistance when used to treat
      selected aortic infections.

PMID- 24334241
TI  - A comparison of exposure assessment approaches: lung cancer and occupational
      asbestos exposure in a population-based case-control study.
AB  - OBJECTIVES: In attempts to overcome the limitations of self-reported data in
      occupational health research, job-exposure matrices, which assign exposure by
      occupation, have emerged as an objective approach for assessing occupational
      exposures. On the basis of a lung cancer case-control study conducted in the
      Greater Toronto Area, 1997-2002, assessment of occupational exposure to asbestos
      was compared using self-reports and a general population job-exposure matrix (DOM
      JEM). METHODS: Cases and frequency matched controls provided life-time job
      histories and self-reported exposures to potential lung carcinogens including
      asbestos through a detailed questionnaire. Exposure to asbestos was also assigned
      to each job by linking occupational histories with DOM-JEM. Agreement in
      classification of exposed and unexposed jobs according to self-reports and DOM
      JEM was evaluated using Cohen's kappa. Risks for lung cancer were estimated using
      unconditional logistic regression for each exposure assessment approach. RESULTS:
      The prevalence of occupational asbestos exposure was greater when based on DOM
      JEM than when based on self-reports. Agreement in classifying exposure to jobs
      between the two assessment approaches was poor. The risk of lung cancer was not
      elevated among workers who self-reported asbestos exposure, whereas workers
      considered exposed on the basis of DOM-JEM were almost twice as likely as
      unexposed workers to be diagnosed with lung cancer (OR 1.9, 95% CI 1.3 to 2.7).
      CONCLUSIONS: It is generally assumed by epidemiologists that self-reported
      exposure assessments result in inflated risk estimates. In this study, self
      reports found no association with a well-established risk factor, whereas a high
      quality job-exposure matrix revealed relative risk estimates that are more
      consistent with previous findings.

PMID- 24334243
TI  - Channel catfish hemoglobin genes: identification, phylogenetic and syntenic
      analysis, and specific induction in response to heat stress.
AB  - Hemoglobins transport oxygen from gill to inner organs in fish, and this process
      is affected by temperature, one of the major environmental factors for fish. The
      hemoglobin gene clusters have been well studied in humans and several model fish
      species, but remain largely unknown in catfish. Here, eight alpha- and six beta
      hemoglobin genes were identified and characterized in channel catfish. Genomic
      synteny analysis showed that these hemoglobin genes were separated into two
      unlinked clusters, the MN cluster containing six alpha- and six beta-hemoglobin
      genes, and the LA cluster consisting of two alpha-hemoglobin genes. Channel
      catfish hemoglobin genes were ubiquitously expressed in all the 10 tested tissues
      from healthy fish, but exhibited higher expression level in spleen, head kidney,
      and trunk kidney. In response to heat stress, hemoglobin genes, especially MN
      Hbalpha4, MN Hbalpha5, MN Hbalpha6, MN Hbbeta4, MN Hbbeta5, MN Hbbeta6, LA
      Hbalpha1, and LA Hbalpha2, presumably the embryonic hemoglobin genes, were
      drastically up-regulated in the gill and head kidney of heat-tolerant fishes, but
      not in these tissues of the heat-intolerant fish, suggesting the importance of
      the embryonic hemoglobin genes in coping with the low oxygen conditions under
      heat stress. 

PMID- 24334242
TI  - A randomised trial of ondansetron for the treatment of irritable bowel syndrome
      with diarrhoea.
AB  - BACKGROUND: Irritable bowel syndrome with diarrhoea (IBS-D) is particularly
      debilitating due to urgency and episodic incontinence. Some 5-hydroxytryptamine 3
      (5-HT3) receptor antagonists (5-HT3RAs) have proven effective but have serious
      side effects. Ondansetron, also a 5-HT3RA, has been widely used as an antiemetic
      with an excellent safety record for over two decades. Our aim was to assess its
      effectiveness in IBS-D. METHODS: 120 patients meeting Rome III criteria for IBS-D
      entered a randomised, double-blind, placebo-controlled crossover study of 5 weeks
      of ondansetron 4 mg versus placebo with dose titration allowed, up to two tablets
      three times daily in the first 3 weeks. Patients completed daily diaries
      documenting stool consistency using the Bristol Stool Form score. Gut transit was
      measured in the last week of each treatment. The primary endpoint was average
      stool consistency in the last 2 weeks of treatment. RESULTS: Ondansetron
      significantly improved stool consistency (mean difference in stool form between
      ondansetron and placebo -0.9, 95% CI -1.1 to -0.6, p<0.001). Compared with
      placebo, patients on ondansetron experienced fewer days with urgency (p<0.001),
      lower urgency scores (p<0.001), reduced frequency of defaecation (p=0.002) and
      less bloating (p=0.002), although pain scores did not change significantly. IBS
      symptom severity score fell more with ondansetron than placebo (83+/-9.8 vs 37+/
      9.7, p=0.001). 65% reported adequate relief with ondansetron but not placebo
      compared with 14% reporting relief with placebo but not ondansetron, relative
      risk 4.7, 95% CI 2.6 to 8.5, p<0.001. CONCLUSIONS: Ondansetron relieves some of
      the most intrusive symptoms of IBS-D, namely loose stools, frequency and urgency.

PMID- 24334244
TI  - Retronychia : four new cases.
AB  - Retronychia (RN) refers to the incarnation of the nail plate in the proximal nail
      fold. We report four clinical cases of this little-known pathology, where there
      may be a long delay in diagnosis. RN exhibits a triad of clinical features, which
      are chronic paronychia, liquid discharge from under the nail fold and disruption
      of the linear nail growth. Chronic paronychia is often confused with bacterial or
      fungal infection. Empirical antibiotic treatment is not useful. Nail plate
      avulsion is the diagnostic and curative procedure of choice. Subsequent nail
      growth is normal without dystrophia and no recurrences are observed. Knowledge of
      this pathology avoids misdiagnosis, unnecessary antibiotic or local treatments
      and allows adequate surgical management. 

PMID- 24334245
TI  - Human fertilization: epididymal hCRISP1 mediates sperm-zona pellucida binding
      through its interaction with ZP3.
AB  - Human epididymal CRISP1 (hCRISP1) associates with sperm during maturation and
      participates in gamete fusion through egg complementary sites. Its homology with
      both rodent epididymal CRISP1 and CRISP4 reported to participate in the previous
      stage of sperm binding to the zona pellucida (ZP), led us to further investigate
      the functional role of hCRISP1 by studying its involvement in human sperm-ZP
      interaction. Human hemizona (HZ) were inseminated with human capacitated sperm in
      the presence of either anti-hCRISP1 polyclonal antibody to inhibit sperm hCRISP1,
      or bacterially-expressed hCRISP1 (rec-hCRISP1) to block putative hCRISP1 binding
      sites in the ZP. Results revealed that both anti-hCRISP1 and rec-hCRISP1 produced
      a significant inhibition in the number of sperm bound per HZ compared with the
      corresponding controls. The finding that neither anti-hCRISP1 nor rec-hCRISP1
      affected capacitation-associated events (i.e. sperm motility, protein tyrosine
      phosphorylation or acrosome reaction) supports a specific inhibition at the sperm
      egg interaction level. Moreover, immunofluorescence experiments using human ZP
      intact eggs revealed the presence of complementary sites for hCRISP1 in the ZP.
      To identify the ligand of hCRISP1 in the ZP, human recombinant proteins ZP2, ZP3
      and ZP4 expressed in insect cells were co-incubated with hCRISP1 and protein
      protein interaction was analyzed by ELISA. Results revealed that rec-hCRISP1
      mainly interacted with ZP3 in a dose-dependent and saturable manner, supporting
      the specificity of this interaction. Altogether, these results indicate that
      hCRISP1 is a multifunctional protein involved not only in sperm-egg fusion but
      also in the previous stage of sperm-ZP binding through its specific interaction
      with human ZP3. 

PMID- 24334246
TI  - Programmed cell death-associated gene transcripts in bovine embryos exposed to
      bovine Herpesvirus type 5.
AB  - In vitro-produced bovine embryos become infected after exposure to bovine
      Herpesvirus type 5 (BoHV-5), yet no changes in developmental rates, mitochondrial
      activity and inhibition of apoptosis are detected in comparison to unexposed
      embryos. Thus, the aim of the present study was to assess the transcription of
      mitochondria-mediated apoptosis genes using TaqMan real-time polymerase chain
      reaction. Transcripts of mcl-1, caspase-2, -3, Apaf-1 and Bax genes were measured
      after exposure to BoHV-5 in vitro. Mitochondrial dehydrogenase activity was
      evaluated by MTT test and compared between groups of exposed and unexposed
      embryos, at day 7 of development. The rate of oocyte maturation was assessed by
      the extrusion of the first polar body. In summary, BoHV-5 exposed embryos
      retained their viability, mitochondrial dehydrogenase activity and displayed up
      regulation of transcription of survival mcl-1 gene and down-regulation of Bax
      transcription in relation to mitochondria-mediated pathway which might improve
      embryo viability. These findings demonstrate that BoHV-5 exposed embryos maintain
      their viability and mitochondrial dehydrogenase activity with no compromise of
      embryos produced in vitro.

PMID- 24334247
TI  - How many diagnosis fields are needed to capture safety events in administrative
      data? Findings and recommendations from the WHO ICD-11 Topic Advisory Group on
      Quality and Safety.
AB  - OBJECTIVE: As part of the WHO ICD-11 development initiative, the Topic Advisory
      Group on Quality and Safety explores meta-features of morbidity data sets, such
      as the optimal number of secondary diagnosis fields. DESIGN: The Health Care
      Quality Indicators Project of the Organization for Economic Co-Operation and
      Development collected Patient Safety Indicator (PSI) information from
      administrative hospital data of 19-20 countries in 2009 and 2011. We investigated
      whether three countries that expanded their data systems to include more
      secondary diagnosis fields showed increased PSI rates compared with six countries
      that did not. Furthermore, administrative hospital data from six of these
      countries and two American states, California (2011) and Florida (2010), were
      analysed for distributions of coded patient safety events across diagnosis
      fields. RESULTS: Among the participating countries, increasing the number of
      diagnosis fields was not associated with any overall increase in PSI rates.
      However, high proportions of PSI-related diagnoses appeared beyond the sixth
      secondary diagnosis field. The distribution of three PSI-related ICD codes was
      similar in California and Florida: 89-90% of central venous catheter infections
      and 97-99% of retained foreign bodies and accidental punctures or lacerations
      were captured within 15 secondary diagnosis fields. CONCLUSIONS: Six to nine
      secondary diagnosis fields are inadequate for comparing complication rates using
      hospital administrative data; at least 15 (and perhaps more with ICD-11) are
      recommended to fully characterize clinical outcomes. Increasing the number of
      fields should improve the international and intra-national comparability of data
      for epidemiologic and health services research, utilization analyses and quality
      of care assessment.

PMID- 24334249
TI  - Eruptive naevi and darkening of pre-existing naevi 24 h after a single mono-dose
      injection of melanotan II.

PMID- 24334250
TI  - What Leonardo missed: a lesson for today.

PMID- 24334248
TI  - A rehabilitation tool designed for intensive web-based cognitive training:
      description and usability study.
AB  - BACKGROUND: Cognitive deficits are among the most disabling of neurological
      diseases and have a serious impact on the quality of life of patients and
      families. Cognitive training has been proven successful in improving or
      compensating for neuropsychological deficits after acute brain injury, but its
      efficacy highly depends on the intensity of treatment over an extended period of
      time. Therefore, cognitive training indicates expensive human resources and
      renders the rehabilitation process vulnerable to physical and economic barriers
      for the majority of patients. OBJECTIVE: The aim of this study was to develop and
      test a new Web-based rehabilitation tool that provides intensive cognitive
      training at home under clinical prescription and monitoring, at affordable costs.
      METHODS: From a pool of 60 original exercises, designed and used over the past 10
      years for cognitive training at our center, we developed 27 exercises on a
      computer game format, with automatic increase or decrease of difficulty levels.
      These exercises were assembled in a clean, user-friendly design and covered
      various cognitive domains such as attention (n=4), memory (n=11), language (n=3),
      calculus (n=3), praxis (n=2), and executive functions (n=3). A Web 2.0 platform
      was also designed to provide medical prescription of cognitive training sessions,
      performed at the patient's home. These sessions included continuous monitoring of
      compliance, performance, and evolution; algorithms for automatic adjustment and
      long-term learning through use, and database recording of all activities. The end
      user interaction test included 80 patients from our memory clinic from several
      groups including subjective memory complaints (n=20), traumatic brain injury
      (n=20), stroke and other static brain lesions (n=20), and mild Alzheimer's
      disease (n=20). During a 1-hour session, patients and their relatives were taught
      to use the system and allowed to practice using it. At the end of the session,
      they were asked to complete a questionnaire. RESULTS: A total of 48/80 patients
      (60%) attended the training session. The mean age of the patients was 60 years
      (SD 13.3, range 41-78), and the mean level of formal education was 6 years (range
      4-16). Of all the participants, 32/48 patients (66%) have previously used a
      computer. All patients and their relatives made a positive evaluation of the
      cognitive training tool. Only 2/48 patients (4%) were not interested in
      performing the exercises at home; 19/48 patients (39%) mentioned the need for
      further coaching from a relative or health care professional. The patients who
      mentioned difficulties in performing the exercises have not used the computer
      earlier. CONCLUSIONS: This new Web-based system was very well accepted by
      patients and their relatives, who showed high levels of motivation to use it on a
      daily basis at home. The simplicity of its use and comfort were especially
      outlined. This tool will have an important effect on human resource management,
      in increasing the patient access to specialized health care and improving the
      quality and national health system costs of rehabilitation programs.

PMID- 24334251
TI  - Nutrient deprivation increases vulnerability of endothelial cells to
      proinflammatory insults.
AB  - Nutrient deprivation is a stimulus for oxidative stress and is an established
      method for induction of cell autophagy and apoptosis. The aims of this study were
      to identify conditions that evoke superoxide production in cultured human
      umbilical vein endothelial cells (HUVECs), determine the mechanism of action for
      this response, and examine whether the stimulus might facilitate the adhesion of
      human isolated neutrophils to the HUVECs. HUVECs were incubated in M199 medium
      under conditions of serum starvation (serum-free M199 medium), low serum (medium
      containing 2% fetal calf serum), and high serum (medium containing 20% fetal calf
      serum). HUVECs were also incubated under proinflammatory conditions, in medium
      supplemented with 50ng/ml tumor necrosis factor-alpha (TNF-alpha) or neutrophils
      preactivated with 10nM phorbol 12-myristate 13-acetate (PMA). Superoxide
      production was increased fourfold in serum-starved HUVECs compared to cells
      incubated in 20% medium, and this was reduced by inhibitors of the mitochondrial
      electron transport chain and mitochondrial Ca(2+) uniporter. Superoxide
      production was 23.6% higher in HUVECs incubated with TNF-alpha in 2% medium
      compared to 2% medium alone, but unchanged with TNF-alpha in 20% medium. PMA
      activated neutrophils adhered to morphologically aberrant HUVECs, which were
      mainly evident under the low-serum condition. The findings show a role of
      mitochondrial enzymes in superoxide production in response to nutrient
      deprivation and suggest that proinflammatory responses in HUVECs become manifest
      when HUVECs are in an already-compromised state. 

PMID- 24334252
TI  - Regulation of sarcoplasmic reticulum Ca(2+) release by cytosolic glutathione in
      rabbit ventricular myocytes.
AB  - Of the major cellular antioxidant defenses, glutathione (GSH) is particularly
      important in maintaining the cytosolic redox potential. Whereas the healthy
      myocardium is maintained at a highly reduced redox state, it has been proposed
      that oxidation of GSH can affect the dynamics of Ca(2+)-induced Ca(2+) release.
      In this study, we used multiple approaches to define the effects of oxidized
      glutathione (GSSG) on ryanodine receptor (RyR)-mediated Ca(2+) release in rabbit
      ventricular myocytes. To investigate the role of GSSG on sarcoplasmic reticulum
      (SR) Ca(2+) release induced by the action potential, we used the thiol-specific
      oxidant diamide to increase intracellular GSSG in intact myocytes. To more
      directly assess the effect of GSSG on RyR activity, we introduced GSSG within the
      cytosol of permeabilized myocytes. RyR-mediated Ca(2+) release from the SR was
      significantly enhanced in the presence of GSSG. This resulted in decreased steady
      state diastolic [Ca(2+)]SR, increased SR Ca(2+) fractional release, and increased
      spark- and non-spark-mediated SR Ca(2+) leak. Single-channel recordings from
      RyR's incorporated into lipid bilayers revealed that GSSG significantly increased
      RyR activity. Moreover, oxidation of RyR in the form of intersubunit crosslinking
      was present in intact myocytes treated with diamide and permeabilized myocytes
      treated with GSSG. Blocking RyR crosslinking with the alkylating agent N
      ethylmaleimide prevented depletion of SR Ca(2+) load induced by diamide. These
      findings suggest that elevated cytosolic GSSG enhances SR Ca(2+) leak due to
      redox-dependent intersubunit RyR crosslinking. This effect can contribute to
      abnormal SR Ca(2+) handling during periods of oxidative stress. 

PMID- 24334254
TI  - Comparative genomic analysis of Saccharomyces cerevisiae yeasts isolated from
      fermentations of traditional beverages unveils different adaptive strategies.
AB  - Saccharomyces cerevisiae strains are the main responsible of most traditional
      alcohol fermentation processes performed around the world. The characteristics of
      the diverse traditional fermentations are very different according to their sugar
      composition, temperature, pH or nitrogen sources. During the adaptation of yeasts
      to these new environments provided by human activity, their different
      compositions likely imposed selective pressures that shaped the S. cerevisiae
      genome. In the present work we performed a comparative genomic hybridization
      analysis to explore the genome constitution of six S. cerevisiae strains isolated
      from different traditional fermentations (masato, mescal, cachaca, sake, wine,
      and sherry wine) and one natural strain. Our results indicate that gene copy
      numbers (GCN) are very variable among strains, and most of them were observed in
      subtelomeric and intrachromosomal gene families involved in metabolic functions
      related to cellular homeostasis, cell-to-cell interactions, and transport of
      solutes such as ions, sugars and metals. In many cases, these genes are not
      essential but they can play an important role in the adaptation to new
      environmental conditions. However, the most interesting result is the association
      observed between GCN changes in genes involved in the nitrogen metabolism and the
      availability of nitrogen sources in the different traditional fermentation
      processes. This is clearly illustrated by the differences in copy numbers not
      only in gene PUT1, the main player in the assimilation of proline as a nitrogen
      source, but also in CAR2, involved in arginine catabolism. Strains isolated from
      fermentations where proline is more abundant contain a higher number of PUT1
      copies and are more efficient in assimilating this amino acid as a nitrogen
      source. A strain isolated from sugarcane juice fermentations, in which arginine
      is a rare amino acid, contains less copies of CAR2 and showed low efficiency in
      arginine assimilation. These results suggest that nitrogen metabolism has played
      an important role in the adaptive evolution of S. cerevisiae strains. 

PMID- 24334253
TI  - Mn porphyrin in combination with ascorbate acts as a pro-oxidant and mediates
      caspase-independent cancer cell death.
AB  - Resistance to therapy-mediated apoptosis in inflammatory breast cancer, an
      aggressive and distinct subtype of breast cancer, was recently attributed to
      increased superoxide dismutase (SOD) expression, glutathione (GSH) content, and
      decreased accumulation of reactive species. In this study, we demonstrate the
      unique ability of two Mn(III) N-substituted pyridylporphyrin (MnP)-based SOD
      mimics (MnTE-2-PyP(5+) and MnTnBuOE-2-PyP(5+)) to catalyze oxidation of
      ascorbate, leading to the production of excessive levels of peroxide, and in turn
      cell death. The accumulation of peroxide, as a consequence of MnP+ascorbate
      treatment, was fully reversed by the administration of exogenous catalase,
      showing that hydrogen peroxide is essential for cell death. Cell death as a
      consequence of the action of MnP+ascorbate corresponded to decreases in GSH
      levels, prosurvival signaling (p-NF-kappaB, p-ERK1/2), and in expression of X
      linked inhibitor of apoptosis protein, the most potent caspase inhibitor.
      Although markers of classical apoptosis were observed, including PARP cleavage
      and annexin V staining, administration of a pan-caspase inhibitor, Q-VD-OPh, did
      not reverse the observed cytotoxicity. MnP+ascorbate-treated cells showed nuclear
      translocation of apoptosis-inducing factor, suggesting the possibility of a
      mechanism of caspase-independent cell death. Pharmacological ascorbate has
      already shown promise in recently completed phase I clinical trials, in which its
      oxidation and subsequent peroxide formation was catalyzed by endogenous
      metalloproteins. The catalysis of ascorbate oxidation by an optimized metal-based
      catalyst (such as MnP) carries a large therapeutic potential as an anticancer
      agent by itself or in combination with other modalities such as radio- and
      chemotherapy. 

PMID- 24334255
TI  - Bcrp1;Mdr1a/b;Mrp2 combination knockout mice: altered disposition of the dietary
      carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and its
      genotoxic metabolites.
AB  - The multidrug transporters breast cancer resistance protein (BCRP), multidrug
      resistance protein 1 (MDR1), and multidrug-resistance-associated protein (MRP) 2
      and 3 eliminate toxic compounds from tissues and the body and affect the
      pharmacokinetics of many drugs and other potentially toxic compounds. The food
      derived carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is
      transported by BCRP, MDR1, and MRP2. To investigate the overlapping functions of
      Bcrp1, Mdr1a/b, and Mrp2 in vivo, we generated Bcrp1;Mdr1a/b;Mrp2(-/-) mice,
      which are viable and fertile. These mice, together with Bcrp1;Mrp2;Mrp3(-/-)
      mice, were used to study the effects of the multidrug transporters on the
      pharmacokinetics of PhIP and its metabolites. Thirty minutes after oral or
      intravenous administration of PhIP (1 mg/kg), the PhIP levels in the small
      intestine were reduced 4- to 6-fold in Bcrp1;Mdr1a/b;Mrp2(-/) (-) and
      Bcrp1;Mrp2;Mrp3(-/-) mice compared with wild-type mice. Fecal excretion of PhIP
      was reduced 8- to 20-fold in knockouts. Biliary PhIP excretion was reduced 41
      fold in Bcrp1;Mdr1a/b;Mrp2(-/-) mice. Biliary and small intestine levels of PhIP
      metabolites were reduced in Bcrp1;Mrp2-deficient mice. Furthermore, in both
      knockout strains, kidney levels and urinary excretion of genotoxic PhIP
      metabolites were significantly increased, suggesting that reduced biliary
      excretion of PhIP and PhIP metabolites leads to increased urinary excretion of
      these metabolites and increased systemic exposure. Bcrp1 and Mdr1a limited PhIP
      brain accumulation. In Bcrp1;Mrp2;Mrp3(-/-), but not Bcrp1;Mdr1a/b;Mrp(-/-) mice,
      the carcinogenic metabolites N2-OH-PhIP (2-hydroxyamino-1-methyl-6
      phenylimidazo[4,5-b]pyridine) and PhIP-5-sulfate (a genotoxicity marker)
      accumulated in liver tissue, indicating that Mrp3 is involved in the sinusoidal
      secretion of these compounds. We conclude that Bcrp1, Mdr1a/b, Mrp2, and Mrp3
      significantly affect tissue disposition and biliary and fecal elimination of PhIP
      and its carcinogenic metabolites and may affect PhIP-induced carcinogenesis as a
      result. 

PMID- 24334256
TI  - Beyond phase 3 registration trials: defining safety for triple therapy with
      protease inhibitors in cirrhosis.

PMID- 24334257
TI  - Drosophila protein phosphatase V regulates lipid homeostasis via the AMPK
      pathway.

PMID- 24334258
TI  - Modulating Wnt signaling to improve cell replacement therapy for Parkinson's
      disease.
AB  - Clinical trials have demonstrated the capacity for dopamine neurons, transplanted
      ectopically into the striatum, to structurally integrate, restore dopamine
      transmission, and induce long-term functional benefits for Parkinson's disease
      (PD) patients. Despite this proof of principle, a number of limitations have
      hindered the development of cell replacement therapy over the past 20 years,
      particularly tissue availability, graft survival, and adequate reinnervation of
      the host brain. With a greater understanding of failure in prior clinical trials,
      increased knowledge of midbrain dopamine development (now including Wnts), and
      the development of pluripotent stem cell technologies, we are better equipped
      than ever to re-address a number of these challenges. This review summarizes the
      trials, tribulations, and progress in cell replacement therapy for PD. We discuss
      the prospects of modulating canonical and non-canonical Wnt signaling to improve
      cell therapy based upon their roles in dopamine neural development and the adult
      brain. This will include the potential of Wnts to (i) expand fetally derived
      tissue in vitro and following transplantation, (ii) promote the differentiation
      of pluripotent stem cells, (iii) increase graft integration and restoration of
      neural circuitry, and finally (iv) enhance graft survival. 

PMID- 24334259
TI  - ZIP-seq: genome-wide mapping of trinucleotide repeats at single-base resolution.

PMID- 24334260
TI  - Association between high temperature and work-related injuries in Adelaide, South
      Australia, 2001-2010.
AB  - OBJECTIVES: (1) To investigate the association between temperature and work
      related injuries and (2) to identify groups of workers at high risk of work
      related injuries in hot environments in Adelaide, South Australia. METHODS:
      Workers' compensation claims in Adelaide, South Australia for 2001-2010 were
      used. The relationship between temperature and daily injury claims was estimated
      using a generalised estimating equation model. A piecewise linear spline function
      was used to quantify the effect of temperature on injury claims below and above
      thresholds. RESULTS: Overall, a 1 degrees C increase in maximum temperature
      between 14.2 degrees C and 37.7 degrees C was associated with a 0.2% increase in
      daily injury claims. Specifically, the incidence rate ratios (IRRs) for male
      workers and young workers aged <=24 were (1.004, 95% CI 1.002 to 1.006) and
      (1.005, 95% CI 1.002 to 1.008), respectively. Significant associations were also
      found for labourers (IRR 1.005, 95% CI 1.001 to 1.010), intermediate production
      and transport workers (IRR 1.003, 95% CI 1.001 to 1.005) and tradespersons (IRR
      1.002, 95% CI 1.001 to 1.005). Industries at risk were agriculture, forestry and
      fishing (IRR 1.007, 95% CI 1.001 to 1.013), construction (IRR 1.006, 95% CI 1.002
      to 1.011), and electricity, gas and water (IRR 1.029, 95% CI 1.002 to 1.058).
      CONCLUSIONS: There is a significant association between injury claims and
      temperature in Adelaide, South Australia, for certain industries and groups.
      Relevant adaptation and prevention measures are required at both policy and
      practice levels to address occupational exposure to high temperatures.

PMID- 24334261
TI  - Microstructural changes in the substantia nigra of asymptomatic agricultural
      workers.
AB  - Parkinson's disease (PD) is marked by the loss of dopamine neurons in the
      substantia nigra (SN). Although the exact etiology is unknown, sporadic PD is
      hypothesized to be a result of genetic susceptibility interacting with
      environmental insult. Epidemiological studies suggest that pesticide exposure is
      linked to higher PD risk, but there are no studies demonstrating SN changes with
      chronic pesticide exposure in human subjects. Thus, high resolution T2-weighted
      magnetic resonance imaging (MRI) and diffusion tensor (DTI) images were obtained
      from 12 agricultural workers with chronic pesticide exposure, 12 controls, and 12
      PD subjects. Neither controls nor pesticide-exposed subjects, had any
      parkinsonian symptoms. Exposure history to pesticides was assessed by a
      structured questionnaire. DTI measures in the SN, including fractional anisotropy
      (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD),
      were obtained for all subjects and compared among groups. Compared to controls,
      PD patients showed the expected significant changes in all DTI measurements in
      the SN. The pesticide-exposed subjects, compared to controls, had significantly
      lower FA values (p=0.022, after multiple comparisons correction), but no
      significant differences in RD, MD, or AD measures. The study is the first to
      demonstrate microstructural changes in the SN of human subjects with chronic
      pesticide exposure. The changes detected by MRI may mark "one of the hits"
      leading to PD, and underlie the increased risk of PD in pesticide users found in
      epidemiological studies. Further human studies assisted by these imaging markers
      may be useful in understanding the etiology of PD. 

PMID- 24334263
TI  - Paraneoplastic acanthosis nigricans paralleling disease course in a patient with
      mycosis fungoides.

PMID- 24334262
TI  - Adolescent risk-taking as a function of prenatal cocaine exposure and biological
      sex.
AB  - OBJECTIVE: To examine the effects of prenatal cocaine exposure and biological sex
      on adolescent risk-taking while controlling for early environmental risk.
      METHODS: Adolescents (n=114, mean age=16) were grouped according to high and low
      risk-taking propensity as measured by the Balloon Analogue Risk Task (BART).
      Prenatal cocaine exposure was assessed at birth, while environmental risk was
      assessed at three points during early childhood. RESULTS: A binary regression
      analysis indicated that males were 3.5 times more likely than females to be high
      risk-takers. Biological sex and prenatal cocaine exposure interacted such that
      exposed males were most likely to be high risk-takers while exposed females were
      the least likely to be high risk-takers. This pattern held after controlling for
      prenatal alcohol exposure and early environmental risk. Early environmental risk
      did not predict adolescent risk-taking. CONCLUSIONS: These findings complement
      and extend earlier research demonstrating that prenatal cocaine exposure
      interacts with biological sex in domains related to inhibitory control, emotion
      regulation, antisocial behavior, and health risk behaviors during preadolescence.

PMID- 24334264
TI  - Neurocognitive deficits, craving, and abstinence among alcohol-dependent
      individuals following detoxification.
AB  - Alcohol dependence, a chronic relapsing disorder, is characterized by an impaired
      ability to regulate compulsive urges to consume alcohol. Very few empirical
      studies have examined the presence of these executive deficits, how they relate
      to craving, and the enduring nature of these deficits during abstinence. As such,
      the current study aimed to characterize these cognitive deficits within a sample
      of 24 alcohol-dependent participants post-detoxification and 23 non-alcohol
      dependent participants. Participants were administered the Sustained Attention to
      Response Task to measure response inhibition and sustained attention and the
      Random Number Generation Task to examine executive deficits. Correlations between
      cognitive performance and clinical measures of alcohol dependence were examined.
      As predicted, the alcohol-dependent group exhibited poorer performance across the
      domains of response inhibition, executive function, and attentional control.
      Cognitive performance was related to clinical measures of craving and years of
      alcohol consumption, whereas the duration of abstinence was not associated with
      improved cognitive performance. These findings highlight the need for therapeutic
      strategies to target these enduring neurocognitive deficits in improving the
      treatment of alcohol dependence. 

PMID- 24334265
TI  - A novel microscopy-based high-throughput screening method to identify proteins
      that regulate global histone modification levels.
AB  - Posttranslational modifications of histones play an important role in the
      regulation of gene expression and chromatin structure in eukaryotes. The balance
      between chromatin factors depositing (writers) and removing (erasers) histone
      marks regulates the steady-state levels of chromatin modifications. Here we
      describe a novel microscopy-based screening method to identify proteins that
      regulate histone modification levels in a high-throughput fashion. We named our
      method CROSS, for Chromatin Regulation Ontology SiRNA Screening. CROSS is based
      on an siRNA library targeting the expression of 529 proteins involved in
      chromatin regulation. As a proof of principle, we used CROSS to identify
      chromatin factors involved in histone H3 methylation on either lysine-4 or lysine
      27. Furthermore, we show that CROSS can be used to identify chromatin factors
      that affect growth in cancer cell lines. Taken together, CROSS is a powerful
      method to identify the writers and erasers of novel and known chromatin marks and
      facilitates the identification of drugs targeting epigenetic modifications. 

PMID- 24334266
TI  - Immunoglobulin G immobilization on PVDF surface.
AB  - Immobilization of antibody molecules onto hydrophobic polymeric surfaces with
      disordered orientation is something unwanted in many applications. To overcome
      this drawback, controlled immunoglobulin G (IgG) immobilization onto
      poly(vinylidene fluoride) surface was investigated in this paper. A two-step
      process involving radiofrequency plasma pretreatment for polymer surface
      functionalization, followed by coupling reaction was developed, after which
      immunoglobulin G was immobilized onto the surface directly or via protein-A. IR
      and XPS data proved that the process is more efficient when the radiofrequency
      plasma pretreatment was performed using N2 and N2/H2 as discharge gases. NIR-CI,
      AFM and XPS surface evaluation revealed that immobilization of IgG onto N2/H2
      plasma-treated PVDF via grafted protein-A was achieved with an ends-on
      orientation, leaving available the antigen binding sites of IgG. This procedure
      could be a promising route for the preparation of oriented IgG assembly onto
      PVDF, useful in biomedical, membranes or sensors applications. QCM results showed
      a better antibody-antigen interaction when IgG immobilization onto PVDF substrate
      is mediated by protein A. 

PMID- 24334267
TI  - Acridine orange coated magnetic nanoparticles for nucleus labeling and DNA
      adsorption.
AB  - The magnetic-fluorescent nanoparticles are the integration of fluorophores and
      magnetic nanoparticles (MNP), which are superior to traditional single-modal
      nanoparticles. Here, we develop magnetic nanoparticles functionalized by acridine
      orange (ACO) for labeling nucleus and separating DNA. The ACO, a cell-permeant
      nucleic acid binding dye, is conjugated with amine on magnetic nanoparticles by
      glutaraldehyde-mediated coupling and characterized by TEM and FT-IR. Fluorescence
      spectroscopy, INCell analyzer, and confocal microscopy analyses confirmed the
      fluorescent property of ACO modified MNP. Furthermore, the modified magnetic
      nanoparticles showed strong intracellular fluorescence when incubated with 293T
      cells for a short period of time. The adsorption capacities measured at various
      concentrations showed enhanced adsorption capacities for double or single
      stranded DNA when compared to amine MNP conjugated with glutaraldehyde. The cell
      viability tests of the composite nanoparticles on 293T cells showed low
      cytotoxicity indicating the safeness of the nanoparticles. The modified magnetic
      nanoparticles pave a versatile platform for biological applications such as cell
      labeling and DNA adsorption. 

PMID- 24334268
TI  - Modulation of enzymatic PS synthesis by liposome membrane composition.
AB  - Phosphatidylserine (PS) is a phospholipid known to exert important physiological
      roles in humans. However, this phospholipid (PL) is poorly available as a natural
      source and hardly produced by the chemical route. In this work, PS was obtained
      by transphosphatidylation using phospholipase D (PLD) and PL self-assembled into
      liposomes as the substrates. The aim was to better understand how the liposome
      membrane composition could modulate PS yield. Three lecithins were used as PL
      substrates, one originated from a marine source providing a high amount of n-3
      polyunsaturated fatty acids, and two issued from soya differing in their
      phosphatidylcholine (PC) content. Different parameters such as Ca(2+) content,
      enzyme and L-serine concentrations modulated PS synthesis. The presence of Ca(2+)
      increased PS conversion yield. The alcohol acceptor (L-serine) concentration
      positively acted on PL conversion, by governing the equilibrium between
      transphosphatidylation and hydrolysis. Beside these specific reaction conditions,
      it was demonstrated that the membrane composition of the liposomes modulated PS
      synthesis. A direct correlation between PS accumulation and the amount of
      cholesterol or alpha-tocopherol incorporated into the soya lecithins was
      observed. This result was interpreted in terms of "head" spacers promoting PLD
      transphosphatidylation. On the whole, this work provided key parameters for the
      formulation of liposomes using enzymatic PLD technology, to produce lecithins
      enriched in different proportions of PS and esterified with various types of
      fatty acids depending on the initial lecithin source.

PMID- 24334269
TI  - Nanocapsules based on mPEGylated artesunate prodrug and its cytotoxicity.
AB  - mPEGylated artesunate prodrug was synthesized via esterification between
      poly(ethylene glycol) monomethyl ether (mPEG) and artesunate (ART). The product
      was inclined to form nanocapsules in aqueous media due to its amphiphilic nature.
      These nanocapsules showed narrow size distribution, with an average particle size
      of 88.7 nm measured by dynamic laser scattering (DLS). Their vesical morphology
      was further confirmed by transmission electron microscopy (TEM). We found that
      the release of ART from the nanocapsules was controllable, which was contributed
      to the easily hydrolyzed property of the ester bond. In addition, the
      cytotoxicity of the prodrug against L1210 and MCF7 cell lines showed an essential
      decrease compared with the free ART. These results present a new strategy in
      designing anti-tumor ART nanocapsules for targeting tumor cells.

PMID- 24334270
TI  - Control of a tumor suppressor PDCD4: Degradation mechanisms of the protein in
      hepatocellular carcinoma cells.
AB  - In this study, we demonstrate that EGF inhibits the TGF-beta1-induced apoptosis
      of Huh7 cells. TGF-beta1 up-regulates the expression of PDCD4 causing apoptosis,
      by stimulating the synthesis of PDCD4 mRNA via the Smad signaling pathway. TGF
      beta1 also inhibits the activation of S6 kinase 1 which phosphorylates the serine
      67 residue of PDCD4 and leads to the phosphorylation of serine 71 and serine 76
      in the beta-TRCP binding sequence. This phosphorylation sequence causes the
      protein to be degraded in the ubiquitin-proteasome system. EGF activates S6
      kinase 1 via the PI3K-Akt-mTOR signaling pathway and stimulates the degradation
      of PDCD4. EGF also suppresses PDCD4 mRNA levels. As the mTOR inhibitor rapamycin
      up-regulated PDCD4 mRNA levels, the PI3K-Akt-mTOR signaling pathway may control
      the transcription of the PDCD4 gene as well as the degradation of the protein.
      TPA also inhibited the TGF-beta1-induced apoptosis of Huh7 cells, stimulating the
      degradation of the PDCD4-protein. Analyses using PDCD4 mutants with changes of
      serines 67, 71 and 76 to alanine revealed that the phosphorylation of serine 67
      is not essential for the TPA-induced suppression of the protein. The mitogens
      could not suppress the PDCD4-mutant proteins with changes of serine 71 and/or
      serine 76 to alanine, however, indicating that phosphorylations at these residues
      are necessary for the proteasome-mediated degradation of PDCD4. The phosphor
      mimic S71/D and S76/D mutants were able to be degraded in the ubiquitin
      proteasome system unlike the mutants with changes of serine to alanine. The
      expression of S71/D mutant was suppressed with EGF but that of S76/D mutant was
      not indicating that at least partly the phosphorylation of both sites was
      mediated by different enzymes. 

PMID- 24334271
TI  - Reproductive choice, enhancement, and the moral continuum argument.
AB  - It is often argued that it does not matter morally whether biomedical
      interventions treat or prevent diseases or enhance nondisease traits; what
      matters is whether and how much they promote well-being. Therapy and enhancement
      both promote well-being, the argument goes, so they are not morally distinct but
      instead continuous. I provide three reasons why this argument should be rejected
      when it is applied to choices concerning the genetic makeup of future people.
      First, it rests on too simple a conception of the badness of disease. Second, it
      wrongly assumes that disease avoidance and enhancement can proceed with similar
      accuracy. Third, it overlooks that disease avoidance tends to be more urgent than
      enhancement from the point of view of distributive justice. Although none of
      these reasons establishes a firm therapy-enhancement distinction, they show that
      a continuum model is not an attractive alternative. 

PMID- 24334272
TI  - Incidence and risk factors for turf toe injuries in intercollegiate football:
      data from the national collegiate athletic association injury surveillance
      system.
AB  - BACKGROUND: Turf toe is the general term for a sprain of the first
      metatarsophalangeal (MTP) joint complex. Previously attributed to shoe design and
      artificial turf, the incidence of turf toe injury has been thought to decline
      with the advent of newer turf designs. However, the current incidence and
      epidemiology remain unknown as the majority of the literature consists of small
      series and addresses diagnosis and treatment rather than epidemiology and
      prevention. METHODS: We examined data from the NCAA's Injury Surveillance System
      (ISS) for 5 football seasons (2004-2005 through 2008-2009), including all
      preseason, regular season, and postseason practice and competition data. The
      incidence, epidemiology, and risk factors for turf toe injury, defined as injury
      to the connective tissue of the first MTP joint, plantar plate complex, and/or
      sesamoid fracture, were determined. RESULTS: The overall incidence of turf toe
      injuries in NCAA football players was 0.062 per 1000 athlete-exposures (A-Es; 95%
      CI 0.052, 0.072). Athletes were nearly 14 times more likely to sustain the injury
      during games compared to practice, with a mean days lost due to injury of 10.1
      (7.9, 12.4). Fewer than 2% of turf toe injuries required operative intervention.
      There was a significantly higher injury rate on third-generation artificial
      surfaces compared to natural grass (0.087 per 1000 A-E [0.067, 0.11] vs 0.047 per
      1000 A-E [0.036, 0.059]). The majority of injuries occurred as a result of
      contact with the playing surface (35.4%) or contact with another player (32.7%),
      and running backs and quarterbacks were the most common positions to suffer turf
      toe injury. CONCLUSION: Our data suggest a significantly higher incidence of turf
      toe injuries during games, a greater susceptibility among running backs and
      quarterbacks, and a significant contribution of playing surface to risk of
      injury. Though turf toe injuries may be less common that previously reported in
      elite football players, these injuries warrant appropriate acute and long-term
      management to prevent long-term dysfunction. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 24334273
TI  - Acute achilles tendon repair: strength outcomes after an acute bout of exercise
      in recreational athletes.
AB  - BACKGROUND: This is the first study to evaluate the effect of an acute bout of
      exercise on strength evaluation after Achilles tendon (AT) rupture and repair.
      METHODS: Forty patients sustained an acute AT injury and met inclusion criteria
      for this study. At a minimum of 12 months after operative repair, patients were
      measured for (1) calf circumference, (2) bilateral isokinetic strength on a Cybex
      dynamometer before and after 30 minutes of walking at 70% maximal exertion, and
      (3) subjective evaluation by AAOS lower limb core and foot and ankle modules.
      Follow-up occurred at a mean of 32.4 +/- 20.7 (range, 12-80) months after
      surgery, and patients were on average 44.4 +/- 8.6 (range, 20-62) years old. One
      tailed Student's paired t tests analyzed significance for strength and fatigue
      between the involved and uninvolved ankle (P < .05). RESULTS: The calf
      circumference of the involved ankle was significantly smaller than the uninvolved
      ankle by 1.9 cm, or 4.7%. Plantarflexion deficits of the involved ankle ranged
      from 12% to 18% for peak torque (P < .0001) and from 17% to 25% for work per
      repetition (P < .0001), but both ankles fatigued at equal proportions as measured
      after exercise. Dorsiflexion strength of the involved ankle increased 6% to 11%
      for peak torque (P = .070) and 1% to 25% for peak work (P = .386). Reported AAOS
      lower limb core and foot and ankle scores averaged 99.8 and 96.0, respectively.
      CONCLUSION: After an AT rupture with repair, patients had less plantarflexion
      strength, and equal dorsiflexion strength in the operative leg compared to the
      uninvolved, normal leg. However, subjective results indicated near normal pain
      and function despite mild plantarflexion strength deficits. Dorsiflexion strength
      was normal after repair and remained normal even after an acute bout of exercise.
      Plantarflexion strength ratios postexercise remained similar to pre-exercise
      after acute exercise bouts. Athletes reported a "flat tire" feeling while
      running, which suggests a probable gait adjustment as cause for long-term
      plantarflexion strength deficits. LEVEL OF EVIDENCE: Level III, cohort study.

PMID- 24334274
TI  - Anatomical evaluation of different approaches for tibiotalocalcaneal arthrodesis.
AB  - BACKGROUND: The transfibular approach is commonly used for tibiotalocalcaneal
      arthrodesis. However, the medial and the posterolateral approaches are available
      as alternatives. The present study was performed to assess the effects of the 3
      approaches on the neurovascular structures encountered and to quantify the extent
      of cartilage in the different joint compartments that could be surgically
      debrided. METHODS: This cadaver study was performed in 6 pairs of formalin-fixed
      legs (mean donor age: 80 years; 4 females, 2 males). For each approach, 4
      specimens were selected. The neurovascular structures at risk and the debrided
      portions of the articular cartilage were compared. RESULTS: Arterial structures
      were least compromised by the transfibular approach. The posterolateral approach
      was particularly likely to damage the lateral malleolar branches of the peroneal
      artery. Venous structures were at risk mainly from the medial approach, which was
      also the most risk-bearing of the 3 approaches in terms of nerve damage. The
      proportions of cartilage-debrided joint surfaces of the tibia in the ankle joint,
      and of the talus and the calcaneus in the subtalar joint, did not differ notably.
      The proportions of debrided surfaces of the talus in the ankle joint differed
      notably among the 3 approaches. CONCLUSIONS: The medial approach could be a valid
      alternative to the lateral transfibular approach for tibiotalocalcaneal
      arthrodesis. Care should be taken, however, to prevent damage to the saphenous
      nerve and other neurological structures. CLINICAL RELEVANCE: Access morbidity and
      feasibility of adequate cartilage debridement are relevant to the clinical
      outcome of hindfoot arthrodesis.

PMID- 24334275
TI  - Minimal incision surgery for tibiotalocalcaneal arthrodesis.
AB  - BACKGROUND: Tibiotalocalcaneal arthrodesis (TTCA) is a salvage procedure for
      severe diseases involving ankle and subtalar joints. However, this procedure is
      often associated with postoperative complications related to preoperative
      comorbidities. The purpose of this study was to present the clinical and
      functional outcomes of a consecutive series of TTCA using an original operative
      approach based on minimal incision surgery (MIS). METHODS: Forty patients were
      followed prospectively for a mean (SD) of 31 (12.5) months. Clinical data, which
      included x-rays, American Orthopaedic Foot and Ankle Society (AOFAS) ankle
      hindfoot score, SF-36 scores, and a patient satisfaction survey, were collected.
      A further 25 patients were examined retrospectively. RESULTS: In the prospective
      group (n = 40), the mean AOFAS score improved by 44.8 points 1 year after the
      intervention (95% confidence interval [CI], 40.6-48.9), and the SF-36 improved by
      a mean of 17.5 points (95% CI, 1.4-20.9) in the mental component summary (MCS)
      score and 11.5 points (95% CI, 8.3-14.7) in the physical component summary (PCS)
      score. In the prospective group, postsurgical pain correlated with MCS score (r =
      0.47, P < .001). In the entire group, bony union (defined as radiographic
      consolidation and absence of clinical symptoms) was observed in 86% of cases. Two
      deep infections, 2 nonunions in patients with preoperative persistent ulcers, and
      7 delayed unions were the major complications observed in the entire group. One
      patient required amputation. No cases of superficial infection, wound dehiscence,
      or deep venous thrombosis were recorded. CONCLUSION: To our knowledge, the
      present series represents the largest study on TTCA using MIS. The data obtained
      in the present study showed clinical and functional improvement after surgery and
      similar bony union rates as previously reported in the literature but with fewer
      complications related to the surgical wounds. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 24334276
TI  - Photocontrol of mitotic kinesin Eg5 facilitated by thiol-reactive photochromic
      molecules incorporated into the loop L5 functional loop.
AB  - Kinesin Eg5 is a plus-end-directed microtubule-based motor that is essential for
      bipolar spindle formation during eukaryotic cell division. Loop L5 of mitotic
      kinesin Eg5 is a key region determining ATPase activity and motor function.
      Photochromic molecules undergo reversible isomerization in response to
      ultraviolet and visible light irradiation. We introduced three kinds of
      photochromic molecules, 4-phenylazomaleinanil (PAM), 4-(N-(2-iodoacetyl)amino)-4'
      (N-(2-(N-(triphenylmethyl)amino)acetyl)amino)azobenzene (IATAB) and 3,3-dimethyl
      1-(2-(2-iodoacetoxy)ethyl)-3H-1,2-dihydroindole-2-spiro-2'-(2H)-6'-nitrochromene
      (IASP) into L5 to control the Eg5 ATPase activity using light irradiation. We
      prepared five kinesin Eg5 motor domain mutants, E116C, E118C, Y125C, W127C and
      D130C, which contained a single reactive cysteine residue in loop L5. The ability
      of S-trityl-l-cysteine (STLC), a specific Eg5 inhibitor, to inhibit E116C, W127C
      and D130C was significantly reduced. The photochromic molecules were
      stoichiometrically incorporated into the cysteine residues in L5 of mutants.
      W127C and D130C modified with IASP exhibited reversible ATPase activity
      alterations when subjected to light irradiation-induced photoisomerization. The
      two IASP modified mutants also demonstrated photocontrolled alterations following
      treatment with STLC. Additionally, the ATPase activity of the mutant D130C
      modified with PAM could be photocontrolled. Our findings demonstrate that
      incorporation of photochromic molecules into the key region of loop L5
      facilitates the photocontrol of the function of kinesin Eg5. 

PMID- 24334277
TI  - A hypothesis for the anti-inflammatory and mechanotransduction molecular
      mechanisms underlying acupuncture tendon healing.
AB  - A previous study demonstrated that acupuncture increases the synthesis and
      reorganisation of collagen molecules in rat tendons after injury. Clinical
      studies have shown that acupuncture improves pain and functional activity in
      patients with tendinopathy. However, the molecular mechanisms underlying these
      effects are unknown. Recent studies have shown that acupuncture can modulate both
      anti-inflammatory (AI) and mechanotransduction (MT) molecular pathways. Moreover,
      the modulation of these pathways can increase type I collagen synthesis, which is
      the main factor that influences tendon biomechanical properties. Our hypothesis
      is that acupuncture increases synthesis and subsequent reorganisation of type I
      collagen during tendon healing by concomitant modulation of the Toll-like
      receptor-nuclear factor-kappaB AI pathway, the mitogen-activated protein kinases
      pathway and the Rho/Rac-F-actin MT pathway. Increased collagen synthesis and
      reorganisation requires that at least one acupoint is anatomically connected with
      the site of the injury because of the local tenoblast MT mechanism. Confirmation
      of this hypothesis will increase the knowledge of acupuncture modulation of the
      previously mentioned molecular pathways, and such confirmation may also help to
      establish the relationships between the different types of acupuncture needle
      stimulation and the influence of acupuncture stimuli on pathway activity levels.
      In addition, the downstream therapeutic effects of acupuncture therapy may be
      established. This hypothesis can be verified in a rat tendon healing model, and
      subsequent clinical protocols for tendon healing can be developed and evaluated
      as standalone therapies or as a component of a combination therapy. 

PMID- 24334278
TI  - Identification of a selective agonist for liver X receptor alpha (LXRalpha) via
      screening of a synthetic compound library.
AB  - Liver X receptor alpha (LXRalpha) plays an important role in reverse cholesterol
      transport (RCT), and activation of LXRalpha could reduce atherosclerosis. In the
      present study, we developed a screening method to identify new potential LXRalpha
      agonists using an LXRalpha-GAL4 chimera reporter assay. A novel analogue of N,N
      disubstituted 2,8-diazaspiro[4.5]decane, IMB-151, was identified as an LXRalpha
      agonist by using this method. IMB-151 showed a significant activation effect on
      LXRalpha, with an EC50 value of 1.47 uM. IMB-151 also increased the expression of
      ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7
      macrophages. The upregulating effects of IMB-151 on ABCA1 and ABCG1 markedly
      decreased when coincubated with geranylgeranyl pyrophosphate (GGPP) ammonium salt
      or LXRalpha small interfering RNA (siRNA). Our data indicated that the
      upregulation of ABCA1 and ABCG1 by IMB-151 depended on activation of LXRalpha.
      Moreover, IMB-151 significantly reduced cellular lipid accumulation and increased
      cholesterol efflux in RAW264.7 macrophages. Interestingly, IMB-151 slightly
      increased sterol response element binding protein 1c (SREBP-1c) protein
      expression levels in HepG2 cells compared with TO901317, and this indicated that
      IMB-151 might have less lipogenesis side effect in vivo. These results suggested
      that IMB-151 was identified as a selective agonist for LXRalpha by using a
      screening method and could be used as a potential antiatherosclerotic lead
      compound in the future. 

PMID- 24334279
TI  - Inhibitory effects of obovatol on osteoclast differentiation and bone resorption.
AB  - Osteoclasts are polykaryons that have the unique capacity to degrade bone.
      Modulation of osteoclast formation and function is a promising strategy for the
      treatment of bone-destructive diseases. Here, we report that obovatol, a natural
      compound isolated from Magnolia obovata, inhibits receptor activator of nuclear
      factor kappa B (NF-kappaB) ligand (RANKL)-induced osteoclast differentiation in
      vitro and inflammatory bone loss in vivo. We found that obovatol strongly
      inhibited osteoclast formation from bone marrow-derived macrophages in a dose
      dependent manner without cytotoxicity. Obovatol significantly suppressed RANKL
      induced activation of NF-kappaB, c-Jun-N-terminal kinase, and extracellular
      signal-regulated kinase signaling pathways. Obovatol also inhibited RANKL-induced
      expression of the genes c-Fos and nuclear factor of activated T cells c1, which
      are transcription factors important for osteoclastogenesis. In addition to
      osteoclast differentiation, obovatol blocked cytoskeletal organization and
      abrogated the bone resorbing activity of mature osteoclast. Obovatol also
      accelerated osteoclast apoptosis through the induction of caspase-3 activation.
      Consistent with its in vitro anti-resorptive effect, obovatol prevented bone loss
      induced by lipopolysaccharide in vivo. Together, our data suggest that obovatol
      may be a useful therapeutic agent for the treatment of pathological bone
      disorders characterized by excessive osteoclastic bone resorption. 

PMID- 24334280
TI  - Development of a novel semi-quantitative analysis system for ultramicroscale
      samples by fluorescent capillary isoelectric focusing.
AB  - Microchemistry provides methods to analyze small quantities of chemical
      substances, including proteins, nucleic acids, and carbohydrates in various
      fields such as biomedical research, tissue engineering, molecular biology, and
      regeneration medicine. We therefore developed a fluorescent capillary isoelectric
      focusing (fluorescent cIEF) system for protein detection at an ultramicroscale
      volume, which aimed to isolate and identify, from a heterogeneous mixture of
      transduced cells, induced pluripotent stem cells (iPSCs) that could be fully
      reprogrammed. In addition, we demonstrated that the SOX2 protein, which is
      indispensable for the acquisition of pluripotency, could be detected by this new
      fluorescent cIEF system to identify iPSCs in the early phase of complete
      reprogramming. This method took less than 1 h for completion, including the time
      required for the antibody-antigen (Ab-Ag) reaction, and required as few as
      approximately three cells. Thus, this system could help improve iPSC generation
      as well as cut costs and reduce workloads.

PMID- 24334281
TI  - Plastic optical fiber-based biosensor platform for rapid cell detection.
AB  - This work presents a novel, fast response time, plastic optic fiber (POF)
      biosensor to detect Escherichia coli. It discloses the technique for the
      development, calibration and measurement of this robust and simple-to-construct
      POF biosensor. The probes in U-shaped format were manufactured with a specially
      developed device. The calibration process led to the evaluation of the
      sensitivity, accuracy and repeatability by using solutions of sucrose for
      obtaining refractive indices (RI) in the range 1.33-1.39 IR equivalent of water
      and bacteria, respectively. The POF probes were functionalized with antibody anti
      E. coli serotype O55 and tested firstly with saline and then with bacterial
      concentrations of 10(4), 10(6), and 10(8) colony forming units/ml (CFU/ml). The
      optoelectronic setup consists of an 880 nm LED connected to the U-shaped probe
      driven by a sine waveform generated by the Simulink (from Matlab((r))). On the
      other side of the probe a photodetector generates a photocurrent which is
      amplified by a transconductance amplifier. The output voltage signal is read by
      the analog-to-digital (A/D) input of the microcontroller. In all tested
      concentrations, the results presented a tendency of a decrease in the output
      signal with time, due to the attachment of the bacteria to the POF probe and
      consequent increase in the RI close to the sensitive area of the fiber surface.
      It has been shown that the system is capable of providing positive response to
      the bacterial concentration in less than 10 min, demonstrating good possibilities
      to be commercially developed as a portable field sensor.

PMID- 24334282
TI  - A portable and chromogenic enzyme-based sensor for detection of abrin poisoning.
AB  - A first of its kind portable, colorimetric detection system has been developed
      for the rapid diagnosis of abrin poisoning. Abrin, a natural biotoxin that is
      homologous to ricin yet more lethal, has high potential for becoming a weapon of
      bioterrorism given its ease of production. Using an immobilization strategy that
      implements non-natural amino acids for site-specific conjugation, we have created
      a reusable N-methyltryptophan oxidase based magnetic bead system that is capable
      of detecting L-abrine, a marker for abrin poisoning, at concentrations as low as
      4 MUM in mock urine. Furthermore, we propose that this detection strategy may be
      readily adaptable for sensing other targets of interest. This unique diagnostic
      test for abrin poisoning has demonstrated key benefits of portability and simple
      visual readout. These significant advantages can thus provide the potential for
      more rapid assessment and corresponding poison management if dedicated toxicology
      laboratories are not an option.

PMID- 24334283
TI  - Electrochemical detection of Francisella tularensis genomic DNA using solid-phase
      recombinase polymerase amplification.
AB  - Solid-phase isothermal DNA amplification was performed exploiting the homology
      protein recombinase A (recA). The system was primarily tested on maleimide
      activated microtitre plates as a proof-of-concept and later translated to an
      electrochemical platform. In both cases, forward primer for Francisella
      tularensis holarctica genomic DNA was surface immobilised via a thiol or an amino
      moiety and then elongated during the recA mediated amplification, carried out in
      the presence of specific target sequence and reverse primers. The formation of
      the subsequent surface tethered amplicons was either colorimetrically or
      electrochemically monitored using a horseradish peroxidase (HRP)-labelled DNA
      secondary probe complementary to the elongated strand. The amplification time was
      optimised to amplify even low amounts of DNA copies in less than an hour at a
      constant temperature of 37 degrees C, achieving a limit of detection of 1.3*10(
      13) M (4*10(6) copies in 50 MUL) for the colorimetric assay and 3.3*10(-14) M
      (2*10(5) copies in 10 MUL) for the chronoamperometric assay. The system was
      demonstrated to be highly specific with negligible cross-reactivity with non
      complementary targets or primers.

PMID- 24334284
TI  - Estimating and testing interactions when explanatory variables are subject to non
      classical measurement error.
AB  - Assessing interactions in linear regression models when covariates have
      measurement error (ME) is complex.We previously described regression calibration
      (RC) methods that yield consistent estimators and standard errors for interaction
      coefficients of normally distributed covariates having classical ME. Here we
      extend normal based RC (NBRC) and linear RC (LRC) methods to a non-classical ME
      model, and describe more efficient versions that combine estimates from the main
      study and internal sub-study. We apply these methods to data from the Observing
      Protein and Energy Nutrition (OPEN) study. Using simulations we show that (i) for
      normally distributed covariates efficient NBRC and LRC were nearly unbiased and
      performed well with sub-study size >=200; (ii) efficient NBRC had lower MSE than
      efficient LRC; (iii) the naive test for a single interaction had type I error
      probability close to the nominal significance level, whereas efficient NBRC and
      LRC were slightly anti-conservative but more powerful; (iv) for markedly non
      normal covariates, efficient LRC yielded less biased estimators with smaller
      variance than efficient NBRC. Our simulations suggest that it is preferable to
      use: (i) efficient NBRC for estimating and testing interaction effects of
      normally distributed covariates and (ii) efficient LRC for estimating and testing
      interactions for markedly non-normal covariates.

PMID- 24334285
TI  - Monitoring training with heart rate-variability: how much compliance is needed
      for valid assessment?
AB  - PURPOSE: To establish the minimum number of days that heart-rate-variability
      (HRV, ie, the natural logarithm of square root of the mean sum of the squared
      differences between R-R intervals, Ln rMSSD) data should be averaged to achieve
      correspondingly equivalent results as data averaged over a 1-wk period. METHODS:
      Standardized changes in Ln rMSSD between different phases of training (normal
      training, functional overreaching (FOR), overall training, and taper) and the
      correlation coefficients of percentage changes in performance vs changes in Ln
      rMSSD were compared when averaging Ln rMSSD from 1 to 7 d, randomly selected
      within the week. RESULTS: Standardized Ln rMSSD changes (90% confidence limits,
      CL) from baseline to overload (FOR) were 0.20 +/- 0.28, 0.33 +/- 0.26, 0.49 +/-
      0.33, 0.48 +/- 0.28, 0.47 +/- 0.26, 0.45 +/- 0.26, and 0.43 +/- 0.29 on days 1 to
      7, respectively. Correlations (90% CL) over the same time sequence and training
      phase were -.02 +/- .23, -.07 +/- .23, -.17 +/- .22, -.25 +/- .22, -.26 +/- .22, 
      .28 +/- .21, and -.25 +/- .22 on days 1 to 7. There were almost perfect quadratic
      relationships between standardized changes/r values vs the number of days Ln
      rMSSD was averaged (r2 = .92 and .97, respectively) in trained triathletes during
      FOR. This indicates a plateau in the increase in standardized changes/r values'
      magnitude after 3 and 4 d, respectively, in trained triathletes. CONCLUSION:
      Practitioners using HRV to monitor training adaptation should use a minimum of 3
      (randomly selected) valid data points per week.

PMID- 24334286
TI  - The benefits of acupuncture: what you think is what you get, or is it?

PMID- 24334288
TI  - Catalytic domain surface residues mediating catecholamine inhibition in tyrosine
      hydroxylase.
AB  - Tyrosine hydroxylase (TH) performs the rate-limiting step in catecholamine (CA)
      synthesis and is a tetramer composed of regulatory, catalytic and tetramerization
      domains. CAs inhibit TH by binding two sites in the active site; one with high
      affinity and one with low affinity. Only high affinity CA binding requires the
      regulatory domain, believed to interact with the catalytic domain in the presence
      of CA. Without a crystal structure of the regulatory domain, the specific areas
      involved in this process are largely undefined. It is not clear whether the
      regulatory domain-catalytic domain interaction is asymmetrical across the
      tetramer to produce the high and low affinity sites. To investigate this, pure
      dimeric TH was generated through double substitution of residues at the
      tetramerization interface and dimerization salt bridge (K170E/L480A). This was
      shown to be the core regulatory unit of TH for CA inhibition, possessing both
      high and low affinity CA binding sites, indicating that there is symmetry between
      dimers of the tetramer. We also examined possible regulatory domain-interacting
      regions on the catalytic domain that mediate high affinity CA binding. Using site
      directed mutagenesis, A297, E362/E365 and S368 were shown to mediate high
      affinity dopamine inhibition through V(max) reduction and increasing the K(M) for
      the cofactor.

PMID- 24334289
TI  - Systematic reviews in bioethics: types, challenges, and value.
AB  - There has recently been interest in applying the techniques of systematic review
      to bioethics literature. In this paper, I identify the three models of systematic
      review proposed to date in bioethics: systematic reviews of empirical bioethics
      research, systematic reviews of normative bioethics literature, and systematic
      reviews of reasons. I argue that all three types yield information useful to
      scholarship in bioethics, yet they also face significant challenges particularly
      in relation to terminology and time. Drawing on my recent experience conducting a
      systematic review, I suggest that complete comprehensiveness may not always be an
      appropriate goal of a literature review in bioethics, depending on the research
      question. In some cases, all the relevant ideas may be captured without capturing
      all the relevant literature. I conclude that systematic reviews in bioethics have
      an important role to play alongside the traditional broadbrush approach to
      reviewing literature in bioethics. 

PMID- 24334290
TI  - Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the
      novel gene GLRX5.
AB  - Patients with nonketotic hyperglycinemia and deficient glycine cleavage enzyme
      activity, but without mutations in AMT, GLDC or GCSH, the genes encoding its
      constituent proteins, constitute a clinical group which we call 'variant
      nonketotic hyperglycinemia'. We hypothesize that in some patients the aetiology
      involves genetic mutations that result in a deficiency of the cofactor lipoate,
      and sequenced genes involved in lipoate synthesis and iron-sulphur cluster
      biogenesis. Of 11 individuals identified with variant nonketotic hyperglycinemia,
      we were able to determine the genetic aetiology in eight patients and delineate
      the clinical and biochemical phenotypes. Mutations were identified in the genes
      for lipoate synthase (LIAS), BolA type 3 (BOLA3), and a novel gene glutaredoxin 5
      (GLRX5). Patients with GLRX5-associated variant nonketotic hyperglycinemia had
      normal development with childhood-onset spastic paraplegia, spinal lesion, and
      optic atrophy. Clinical features of BOLA3-associated variant nonketotic
      hyperglycinemia include severe neurodegeneration after a period of normal
      development. Additional features include leukodystrophy, cardiomyopathy and optic
      atrophy. Patients with lipoate synthase-deficient variant nonketotic
      hyperglycinemia varied in severity from mild static encephalopathy to Leigh
      disease and cortical involvement. All patients had high serum and borderline
      elevated cerebrospinal fluid glycine and cerebrospinal fluid:plasma glycine
      ratio, and deficient glycine cleavage enzyme activity. They had low pyruvate
      dehydrogenase enzyme activity but most did not have lactic acidosis. Patients
      were deficient in lipoylation of mitochondrial proteins. There were minimal and
      inconsistent changes in cellular iron handling, and respiratory chain activity
      was unaffected. Identified mutations were phylogenetically conserved, and
      transfection with native genes corrected the biochemical deficiency proving
      pathogenicity. Treatments of cells with lipoate and with mitochondrially-targeted
      lipoate were unsuccessful at correcting the deficiency. The recognition of
      variant nonketotic hyperglycinemia is important for physicians evaluating
      patients with abnormalities in glycine as this will affect the genetic causation
      and genetic counselling, and provide prognostic information on the expected
      phenotypic course. 

PMID- 24334292
TI  - Development and characterisation of a silicon PIN diode array based highly
      sensitive portable continuous radon monitor.
AB  - This paper discusses the development and characterisation of a portable and
      highly sensitive continuous radon monitor (CRM) based on an array of in-house
      developed silicon PIN diode detectors. The development of this system was
      initiated in view of the limitations of the available similar radon measurement
      systems with regards to low sensitivity. The system utilises a hemispherical
      metal chamber (1 L capacity) for active air sampling. A quantitative estimation
      of radon concentration is carried out through alpha spectroscopy of electro
      deposited (222)Rn decay products on the detector surface. The system was
      successfully tested and characterised in laboratory conditions. The
      characterisation experiments included optimisation of sensitivity, calibration
      with respect to linearity and a study of the influence of humidity on its
      performance. The novel PIN diode array design yields a high sensitivity of 1.76
      +/- 0.003 counts h(-1)/(Bq m(-3)) at a relative humidity level of 10% in the
      sampled air, which is more than two times as high as that reported for similar
      commercial systems. This instrument displayed a minimum detectable activity level
      of 0.80 Bq m(-3). 

PMID- 24334291
TI  - Resistance to Dasatinib in primary chronic lymphocytic leukemia lymphocytes
      involves AMPK-mediated energetic re-programming.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the
      western world. Although promising new therapies for this incurable disease are
      being tested in clinical trials, the therapeutic relevance of metabolic rewiring
      in chronic lymphocytic leukemia (CLL) is poorly understood. The aim of this study
      was to identify targetable metabolic differences in primary CLL lymphocytes by
      the use of Dasatinib. Dasatinib is a multi-tyrosine kinase inhibitor used to
      treat chronic myelogenous leukemia (CML) and is being tested in clinical trials
      for several cancers including CLL. This drug has been shown to be beneficial to
      CML patients suffering from diabetes by reducing their glucose plasma levels. In
      keeping with this previous observation, we report that Dasatinib induced glucose
      use while reducing lactate production, suggesting that this tyrosine kinase
      inhibitor decreases aerobic glycolysis and shifts glucose use in primary CLL
      lymphocytes. Our results suggest that primary CLL lymphocytes (independently of
      traditional prognostic factors) can be stratified in two subsets by their
      sensitivity to Dasatinib in vitro. Increased glucose use induced by Dasatinib or
      by inhibition of mitochondrial respiration was not sufficient to sustain survival
      and ATP levels in CLL samples sensitive to Dasatinib. The two subsets of primary
      CLL lymphocytes are characterized as well by a differential dependency on
      mitochondrial respiration and the use of anabolic or catabolic processes to cope
      with induced metabolic/energetic stress. Differential metabolic reprogramming
      between subsets is supported by the contrasting effect on the survival of
      Dasatinib treated CLL lymphocytes with pharmacological inhibition of two master
      metabolic regulators (mTorc1 and AMPK) as well as induced autophagy. Alternative
      metabolic organization between subsets is further supported by the differential
      basal expression (freshly purified lymphocytes) of active AMPK, regulators of
      glucose metabolism and modulators of AKT signaling. The contrasting metabolic
      features revealed by our strategy could be used to metabolically target CLL
      lymphocyte subsets creating new therapeutic windows for this disease for mTORC1
      or AMPK inhibitors. Indeed, we report that Metformin, a drug used to treat
      diabetes was selectively cytotoxic to Dasatinib sensitive samples. Ultimately, we
      suggest that a similar strategy could be applied to other cancer types by using
      Dasatinib and/or relevant tyrosine kinase inhibitors. 

PMID- 24334293
TI  - Use of cerebrospinal fluid enzyme immunoassay for diagnosis of neurosyphilis.
AB  - Neurosyphilis is a difficult clinical stage of syphilis as there is no ideal
      method for diagnosis and workup requires lumbar puncture which may sometimes
      provide ambiguous results especially in HIV co-infected patients. Enzyme
      immunoassay is a widely used screening test for syphilis in serum, but its test
      performance was not well studied in cerebrospinal fluid. To examine the
      diagnostic performance of cerebrospinal fluid-enzyme immunoassay (CSF-EIA) in
      neurosyphilis, we conducted a prospective study for two years. All consecutive
      patients admitted for workup of neurosyphilis under the Social Hygiene Service,
      in Hong Kong, were included. Laboratory tests on CSF included several serological
      tests, CSF cell count, and protein. Forty-five patients were prospectively
      recruited, of which 29 people were living with HIV / AIDS. Using diagnostic case
      definition standard stipulated in the IUSTI 2008 guidelines, 17 patients
      satisfied the diagnosis of neurosyphilis. The CSF-EIA test provided 100% in both
      sensitivity and negative predictive value; its specificity was 46.4% (13/28, 95%
      CI 31.8-61%). Specificity improved to 80.8% (95% CI: 68.4-93.2%) with optical
      density cut-off value at 1.4 for cases with CSF red cell counts <600/mm(3) This
      is the first study on use of CSF-EIA in neurosyphilis. CSF-EIA showed high
      sensitivity and high negative predictive value in the study population and the
      presence of CSF red cells < 600/mm(3)might not affect its accuracy. 

PMID- 24334294
TI  - Combination therapy of hydroxycarbamide with anagrelide in patients with
      essential thrombocythemia in the evaluation of Xagrid(R) efficacy and long-term
      safety study.
AB  - Available information is limited regarding the use of cytoreductive combination
      therapy in high-risk patients with essential thrombocythemia. This analysis aims
      to evaluate the clinical relevance and patterns of cytoreductive combination
      treatment in European high-risk patients with essential thrombocythemia in the
      Evaluation of Xagrid((r)) Efficacy and Long-term Safety study. Of 3643 patients,
      347 (9.5%) received combination therapy. Data were recorded at each 6-month
      update. Of 347 patients who received combination therapy, 304 (87.6%) received
      hydroxycarbamide + anagrelide. Monotherapies received before this combination
      were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly
      doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as
      prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median
      platelet counts were 581 * 10(9)/L and 411 * 10(9)/L before and after starting
      hydroxycarbamide + anagrelide, respectively. In patients with paired data
      (n=153), the number of patients with platelet counts less than 400 * 10(9)/L
      increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less
      than 600 * 10(9)/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide +
      anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide,
      59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another
      therapy added. The most frequent reasons for discontinuation were
      intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination
      therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of
      all high-risk patients with essential thrombocythemia and may be a useful
      approach in treating patients for whom monotherapy is unsatisfactory.
      (Clinicaltrials.gov identifier:NCT00567502).

PMID- 24334295
TI  - The PDK1 master kinase is over-expressed in acute myeloid leukemia and promotes
      PKC-mediated survival of leukemic blasts.
AB  - PDK1 is a master kinase that activates at least six protein kinase groups
      including AKT, PKC and S6K and is a potential target in the treatment of a range
      of malignancies. Here we show overexpression of PDK1 in over 40% of
      myelomonocytic acute leukemia patients. Overexpression of PDK1 occurred uniformly
      throughout the leukemic population, including putative leukemia-initiating cells.
      Clinical outcome analysis revealed PDK1 overexpression was associated with poorer
      treatment outcome. Primary acute myeloid leukemia blasts over-expressing PDK1
      showed improved in vitro survival and ectopic expression of PDK1 promoted the
      survival of myeloid cell lines. Analysis of PDK1 target kinases revealed that
      PDK1 overexpression was most closely associated with increased phosphorylation of
      PKC isoenzymes and inhibition of PKC strongly inhibited the survival advantage of
      PDK1 over-expressing cells. Membrane localization studies implicated PKCalpha as
      a major target for PDK1 in this disease. PDK1 over-expressing blasts showed
      differential sensitivity to PDK1 inhibition (in the low micromolar range)
      suggesting oncogene addiction, whilst normal bone marrow progenitors were
      refractory to PDK1 inhibition at effective inhibitor concentrations. PDK1
      inhibition also targeted subpopulations of leukemic blasts with a putative
      leukemia-initiating cell phenotype. Together these data show that overexpression
      of PDK1 is common in acute myelomonocytic leukemia and is associated with poorer
      treatment outcome, probably arising from the cytoprotective function of PDK1. We
      also show that therapeutic targeting of PDK1 has the potential to be both an
      effective and selective treatment for these patients, and is also compatible with
      current treatment regimes. 

PMID- 24334296
TI  - A Good Manufacturing Practice procedure to engineer donor virus-specific T cells
      into potent anti-leukemic effector cells.
AB  - A sequential, two-step procedure in which T-cell-depleted allogeneic stem cell
      transplantation is followed by treatment with donor lymphocyte infusion at 6
      months can significantly reduce the risk and severity of graft-versus-host
      disease, with postponed induction of the beneficial graft-versus-leukemia effect.
      However, patients with high-risk leukemia have a substantial risk of relapse
      early after transplantation, at a time when administration of donor lymphocytes
      has a high likelihood of resulting in graft-versus-host disease, disturbing a
      favorable balance between the graft-versus-leukemia effect and graft-versus-host
      disease. New therapeutic modalities are, therefore, required to allow early
      administration of T cells capable of exerting a graft-versus-leukemia effect
      without causing graft-versus-host disease. Here we describe the isolation of
      virus-specific T cells using Streptamer-based isolation technology and subsequent
      transfer of the minor histocompatibility antigen HA-1-specific T-cell receptor
      using retroviral vectors. Isolation of virus-specific T cells and subsequent
      transduction with HA-1-T-cell receptor resulted in rapid in vitro generation of
      highly pure, dual-specific T cells with potent anti-leukemic reactivity. Due to
      the short production procedure of only 10-14 days and the defined specificity of
      the T cells, administration of virus-specific T cells transduced with the HA-1-T
      cell receptor as early as 8 weeks after allogeneic stem cell transplantation is
      feasible. (This clinical trial is registered at www.clinicaltrialsregister.eu as
      EudraCT number 2010-024625-20). 

PMID- 24334297
TI  - Low temperature route synthesis of SiC-Al2O3 hetero-structural nanofibers.
AB  - SiC-Al2O3 hetero-structural nanofibers have been synthesized by the chemical
      solution approach at 200  degrees  C. The diameters of nanofibers are in the
      range of 60-100 nm while the lengths are from tens of micrometers to hundreds of
      micrometers. The microstructural analysis shows that the fibers possess a like
      epitaxial relationship between (104) of hexagonal Al2O3 and (111) of cubic SiC.
      Additionally, the optical investigation of the nanofibers suggests there are some
      defects in the low annealing temperature synthesized SiC-Al2O3 nanofibers.

PMID- 24334299
TI  - A comparison of older adults' subjective experiences with virtual and real
      environments during dynamic balance activities.
AB  - The purpose of this study was to explore the subjective experience of older
      adults interacting with both virtual and real environments. Thirty healthy older
      adults engaged with real and virtual tasks of similar motor demands: reaching to
      a target in standing and stepping stance. Immersive tendencies and absorption
      scales were administered before the session. Game engagement and experience
      questionnaires were completed after each task, followed by a semistructured
      interview at the end of the testing session. Data were analyzed respectively
      using paired t tests and grounded theory methodology. Participants preferred the
      virtual task over the real task. They also reported an increase in presence and
      absorption with the virtual task, describing an external focus of attention.
      Findings will be used to inform future development of appropriate game-based
      balance training applications that could be embedded in the home or community
      settings as part of evidence-based fall prevention programs. 

PMID- 24334300
TI  - Streptococcus anginosus, tooth extraction and brain abscess.

PMID- 24334301
TI  - Optimization of K-edge imaging for vulnerable plaques using gold nanoparticles
      and energy resolved photon counting detectors: a simulation study.
AB  - We investigated the effect of different imaging parameters, such as dose, beam
      energy, energy resolution and the number of energy bins, on the image quality of
      K-edge spectral computed tomography (CT) of gold nanoparticles (GNP) accumulated
      in an atherosclerotic plaque. A maximum likelihood technique was employed to
      estimate the concentration of GNP, which served as a targeted intravenous
      contrast material intended to detect the degree of the plaque's inflammation. The
      simulation studies used a single-slice parallel beam CT geometry with an x-ray
      beam energy ranging between 50 and 140 kVp. The synthetic phantoms included small
      (3 cm in diameter) cylinder and chest (33 * 24 cm(2)) phantoms, where both
      phantoms contained tissue, calcium and gold. In the simulation studies, GNP
      quantification and background (calcium and tissue) suppression tasks were
      pursued. The x-ray detection sensor was represented by an energy resolved photon
      counting detector (e.g., CdZnTe) with adjustable energy bins. Both ideal and more
      realistic (12% full width at half maximum (FWHM) energy resolution)
      implementations of the photon counting detector were simulated. The simulations
      were performed for the CdZnTe detector with a pixel pitch of 0.5-1 mm, which
      corresponds to a performance without significant charge sharing and cross-talk
      effects. The Rose model was employed to estimate the minimum detectable
      concentration of GNPs. A figure of merit (FOM) was used to optimize the x-ray
      beam energy (kVp) to achieve the highest signal-to-noise ratio with respect to
      the patient dose. As a result, the successful identification of gold and
      background suppression was demonstrated. The highest FOM was observed at the 125
      kVp x-ray beam energy. The minimum detectable GNP concentration was determined to
      be approximately 1.06 umol mL(-1) (0.21 mg mL(-1)) for an ideal detector and
      about 2.5 umol mL(-1) (0.49 mg mL(-1)) for a more realistic (12% FWHM) detector.
      The studies show the optimal imaging parameters at the lowest patient dose using
      an energy resolved photon counting detector to image GNP in an atherosclerotic
      plaque. 

PMID- 24334302
TI  - Apoptotic circulating tumor cells (CTCs) in the peripheral blood of metastatic
      colorectal cancer patients are associated with liver metastasis but not CTCs.
AB  - Enumeration of circulating tumor cells (CTCs) by the CellSearch system provides
      prognostic information in metastatic colorectal cancer, regardless of metastatic
      site. We found that CTCs generally represent <1% of observed events with
      CellSearch analysis and adapted scoring criteria to classify other peripheral
      blood events. Examination of twenty two metastatic colorectal cancer patients'
      blood revealed that patients with high CEA or liver metastases, but not lung or
      distant lymph node metastases, possessed significant numbers of apoptotic CTCs
      prior to treatment initiation by Fischer's exact test. Six out of eleven patients
      with liver metastasis possessed apoptotic CTCs whereas one of nine patients with
      other metastases had measurable apoptotic CTCs. An elevated CTC number was not
      necessarily associated with apoptotic CTCs or CTC debris by Spearman's
      correlation, suggesting the metastatic site rather than CTCs per se as
      contributing to the origin of these events. 

PMID- 24334303
TI  - Patterns of preoperative laboratory testing in patients undergoing outpatient
      plastic surgery procedures.
AB  - BACKGROUND: Preoperative laboratory testing is commonplace in the clinical
      setting and is often utilized at surgeon discretion. We searched the American
      College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP)
      data set to determine the impact of preoperative laboratory testing in ambulatory
      plastic surgery patients. OBJECTIVE: The authors assess the utilization and
      predictive value of preoperative laboratory testing in outpatient plastic surgery
      procedures. METHODS: Patients undergoing ambulatory plastic surgery were
      identified from the 2005 to 2010 NSQIP databases. Laboratory tests were
      categorized by group: hematologic, chemistry, coagulation, and liver function
      tests (LFT). We defined complications in 2 groups: major postoperative and wound
      complications. Multivariate analyses were used to identify patient
      characteristics associated with testing and to assess the ability of laboratory
      testing to predict postoperative complications. RESULTS: A total of 5359 (62.0%)
      patients underwent testing; 881 (16.4%) tests were performed on the day of
      surgery. In patients with no defined NSQIP comorbidities, 59.4% underwent
      preoperative testing and had a significantly lower rate of abnormal findings
      (33.4% vs 25.3%, P < .0001). In multivariate analyses, testing was associated
      with older age, American Society of Anesthesiologists class >2, Hispanic or
      African American race, body contouring procedures, epidural or spinal procedures,
      and with diabetes, hypertension, and cancer. Major complications occurred in
      0.34% of patients. Our analysis demonstrated that neither testing nor abnormal
      results were associated with postoperative complications, either major (P = .178)
      or wound (P = .150). CONCLUSIONS: We found no association between abnormal
      laboratory testing and postoperative morbidity. Preoperative testing in low-risk
      ambulatory plastic surgery patients may be costly and has limited direct clinical
      benefit.

PMID- 24334304
TI  - Surgical correction of crow's feet deformity with radiofrequency current.
AB  - BACKGROUND: There are many published surgical techniques for the correction of
      crow's feet deformity, but subsequent contour irregularities and early recurrence
      are often reported. OBJECTIVE: The authors present a radiofrequency (RF)
      technique to treat crow's feet that can prevent complications while
      simultaneously maintaining long-term results. METHODS: From April 2010 to
      February 2012, a total of 52 consecutive patients (3 men and 49 women) underwent
      surgical correction of crow's feet with an RF current. Following elevation of the
      skin flap in the temporal area, the lateral portion of the orbicularis oculi
      muscle was partially elevated and splayed. Then the RF current was applied to the
      elevated muscle flap until the target temperature of 60 degrees C to 80 degrees C
      was reached. Clinical outcomes were observed through photographs with patients in
      a natural smiling position. RESULTS: Mean (SD) patient age was 52.7 (2.2) years
      (range, 31-73 years). Patients were followed postoperatively during a mean period
      of 23 months (range, 15-36 months). There were no recurrences of crow's feet
      during the follow-up period. No major complications were noted. CONCLUSIONS: The
      main advantage of this surgical technique is preserving continuity of the
      orbicularis oculi muscle while selectively decreasing muscle tone. Hence, this
      technique may prevent any contour irregularities. The RF current causes
      irreversible muscle fibrosis, which in turn provides long-lasting results. While
      the early results of this series show promising long-term efficacy and a good
      safety profile, the small number of patients and short-term follow-up period
      warrant further study.

PMID- 24334305
TI  - A failsafe method to avoid injury to the great auricular nerve.
AB  - BACKGROUND: The great auricular nerve (GAN) is the most commonly injured nerve
      during facelift surgery. Although rare, injury can result in long-term sequelae.
      OBJECTIVES: Previous reports have described the nerve's location at the midbelly
      of the sternocleidomastoid muscle (SCM) or at its emergence from underneath the
      SCM. The purpose of our study was to identify the superior course of the great
      auricular nerve as it applies to facelift. METHODS: Thirteen fresh cadavers were
      dissected. A vertical line through the midlobule was drawn perpendicular to the
      Frankfort's horizontal, acting as a reference to the course of the GAN.
      Transparent paper overlay tracings were then done to record each nerve's
      location. The distance from the bony external auditory canal (EAC) to the nerve
      was measured at the anterior muscle border, at the midbelly of the SCM, and as
      the nerve emerged from under the SCM. Branching patterns of the nerve and its
      relation to the external jugular vein were identified. RESULTS: In 100% of the
      dissections, the superior course of the GAN fell within a 30-degree angle
      constructed using the vertical limb perpendicular to the Frankfurt horizontal and
      a second limb drawn posteriorly from the midlobule. The distance from the EAC to
      the nerve was 4.9 +/- 1.1 cm at the anterior muscle border, 7.3 +/- 1.0 cm at the
      midbelly of the SCM, and 9.8 +/- 1.2 cm at the GAN's emergence from under the
      SCM. Four types of branching patterns were identified. CONCLUSIONS: The 30-degree
      angle described above rapidly and accurately identifies the nerve's location.

PMID- 24334306
TI  - Semipermanent filler treatment of HIV-positive patients with facial lipoatrophy:
      long-term follow-up evaluating MR imaging and quality of life.
AB  - BACKGROUND: Injectable fillers such as poly-L-lactic acid (PLLA) and calcium
      hydroxylapatite (CaHA) have shown promising results in the treatment of
      combination antiretroviral therapy (cART)-induced facial lipoatrophy (FLA).
      However, the effects of these substances on magnetic resonance imaging (MRI) have
      not yet been described. OBJECTIVE: The authors analyze the association between
      the effects of treatment with semipermanent fillers on MRI and changes in quality
      of life (QOL). METHODS: Eighty-two human immunodeficiency virus (HIV)-positive
      patients with cART-induced FLA (grades 2-4) were enrolled in this prospective
      study. A mean volume of 58.2 mL (range, 12-105 mL) of PLLA (n = 41 patients) and
      9.1 mL (range, 3-23 mL) of CaHA (n = 41) was injected in multiple sessions. The
      MRI examinations were performed prior to treatment and again 12 months after. The
      self-reported severity of FLA as well as QOL was measured using questionnaires
      based on Short Form 36, Medical Outcomes Study HIV Health Survey, and Center for
      Epidemiologic Studies Depression Scale formats. RESULTS: Significant increases in
      total subcutaneous thickness (TST) of the injected regions could be identified on
      MRI in nearly all patients 1 year posttreatment. Patients reported that mental
      health and social and role functioning improved; depressive symptoms decreased
      after treatment. In addition, the increase in TST was positively associated with
      improvement of QOL. CONCLUSIONS: This study confirms that treatment with both
      PLLA and CaHA not only increases TST but also is associated with improved QOL for
      HIV-infected patients. Furthermore, the study also demonstrates that MRI can show
      filler-induced neocollagenesis and quantify FLA treatment effects.

PMID- 24334308
TI  - Balance control during the delivery stride in competitive older age lawn bowlers.
AB  - This project assessed dynamic balance and stability in aged lawn bowlers during
      the delivery stride. Participants were divided into two groups: aged 65 years or
      less (n = 14) and aged over 65 years (n = 16). Standard balance-based center of
      pressure (CoP) and ground reaction force variables were recorded and a Dynamic
      Postural Stability Index (DPSI) was used for calculating during ten deliveries.
      None of the balance variables correlated significantly with age although years of
      bowling experience correlated with DPSI scores (r = -.42, P = .019). The over 65
      group had significantly greater variance in the mediolateral CoP movements, with
      no other significant differences in balance or postural stability variables
      between groups. Analysis of covariance indicated that the DPSI data were
      influenced significantly by bowling experience regardless of age group. It was
      concluded that in older aged lawn bowlers, playing experience rather than age is
      a key determinant of balance control during the lawn bowls delivery action. 

PMID- 24334307
TI  - Adipose-derived stem cell to epithelial stem cell transdifferentiation: a
      mechanism to potentially improve understanding of fat grafting's impact on skin
      rejuvenation.
AB  - BACKGROUND: Recent evidence suggests that lipofilling improves overlying skin
      composition and appearance. Adipose-derived stem cells (ADSC) have been
      implicated. OBJECTIVE: The authors identify ADSC transdifferentiation into
      epithelial stem cells through coexpression of GFP+ (green fluorescent protein
      positive) ADSC with the epithelial stem cell marker p63 in an in vivo fat
      grafting model. METHODS: Six male, GFP+ mice served as adipose tissue donors.
      Twelve nude mice served as recipients. Recipients were subdivided into 2 arms (6
      mice/each arm) and received either whole-fat specimen (group 1) or isolated and
      purified ADSC + peptide hydrogel carrier (group 2) engrafted into a 1-cm(2) left
      parascapular subdermal plane. The right parascapular subdermal plane served as
      control. Skin flaps were harvested at 8 weeks and subjected to (1) confocal
      fluorescent microscopy and (2) reverse transcriptase polymerase chain reaction
      (RT-PCR) for p63 mRNA expression levels. RESULTS: Gross examination of skin flaps
      demonstrated subjectively increased dermal vessel presence surrounding whole-fat
      and ADSC specimens. The GFP+ cells were seen within overlying dermal architecture
      after engraftment and were found to coexpress p63. Significantly increased levels
      of p63 expression were found in the ADSC + hydrogel skin flaps. CONCLUSIONS: We
      offer suggestive evidence that GFP+ ADSC are found within the dermis 8 weeks
      after engraftment and coexpress the epithelial stem cell marker p63, indicating
      that ADSC may transdifferentiate into epithelial stem cells after fat grafting.
      These findings complement current understanding of how fat grafts may rejuvenate
      overlying skin.

PMID- 24334309
TI  - Inverted polymer solar cells with Nafion(r) as the hole extraction layer:
      efficiency and lifetime studies.
AB  - The use of Nafion((r)) as the hole extraction layer in polymer solar cells is
      demonstrated in this work. Inverted devices were built on plastic foil with the
      following architecture: PET/ITO/ZnO/P3HT:PCBM/Nafion((r))/Ag. The Nafion((r)) was
      processed from a surfactant-free solution in alcoholic solvents on top of the
      active layer. Optimization of film thickness and annealing yielded fully
      functional devices with power conversion efficiency similar to others referenced,
      along with good operational stability.

PMID- 24334310
TI  - Gait analysis for foot and ankle surgeons-- topical review, part 2: approaches to
      multisegment modeling of the foot.

PMID- 24334311
TI  - How to use: bacterial cultures in diagnosing lower respiratory tract infections
      in cystic fibrosis.
AB  - Respiratory infections are the leading cause of morbidity and mortality in cystic
      fibrosis. Certain bacteria, such as Pseudomonas aeruginosa, are associated with a
      worse clinical outcome than others, but can be completely eradicated if
      identified and treated early. The diagnosis of lower respiratory tract infections
      can be challenging in the non-expectorating patient, in whom upper airway
      samples, such as cough swabs, are a surrogate for lower airway sampling. However,
      the results of these often do not fit with the clinical picture, presenting a
      management dilemma. Frequently, clinicians are faced with a negative culture
      result in a progressively symptomatic patient and vice versa. When judging the
      clinical significance of a positive upper airway culture result in an
      asymptomatic patient, it is important to consider the prognostic significance of
      the organism cultured. Given that the reported sensitivity of upper airway swabs
      (which includes throat swabs) is variable, ranging from 35.7% to 71% for
      Pseudomonas aeruginosa, 50% to 86% for Staphylococcus aureus and 11% to 92% for
      Haemophilus influenza, upper airway samples may fail to identify lower airway
      infections. Therefore, in symptomatic children, a repeatedly negative upper
      airway swab should not be considered as reassuring, and alternative sampling
      methods, such as induced sputum or bronchoalveolar lavage, should be considered.
      Here we use some examples of common scenarios to illustrate how best to use
      bacterial cultures to aid management decisions in cystic fibrosis.

PMID- 24334312
TI  - Developing a viable alternative to Medicare's physician payment strategy.
AB  - Since 1992 Medicare has reimbursed physicians on a fee-for-service basis that
      weights physician services according to the effort and expense of providing those
      services and converts the weights to dollars using a conversion factor. In 1997
      Congress replaced an existing spending constraint with the Sustainable Growth
      Rate (SGR) to reduce reimbursements if overall physician spending exceeded the
      growth in the economy. Congress, however, has routinely overridden the SGR
      because of concerns that reduced payments to physicians would limit patients'
      access to care. Under continued pressure to override scheduled fee reductions or
      eliminate the SGR altogether, Congress is now considering legislation that would
      reimburse physicians to improve quality and lower costs-two things that the
      current system does not do. This article reviews several promising models,
      including patient-centered medical homes, accountable care organizations, and
      various payment bundling pilots, that could offer lessons for a larger reform of
      physician payment. Pilot projects that focus exclusively on alternative ways to
      reimburse physicians apart from payments to hospitals, such as payments for
      episodes of care, are also needed. Most promising, Congress is now showing
      bipartisan, bicameral interest in revising how Medicare reimburses physicians. 

PMID- 24334313
TI  - Prenatal pharmacotherapy rescues brain development in a Down's syndrome mouse
      model.
AB  - Intellectual impairment is a strongly disabling feature of Down's syndrome, a
      genetic disorder of high prevalence (1 in 700-1000 live births) caused by trisomy
      of chromosome 21. Accumulating evidence shows that widespread neurogenesis
      impairment is a major determinant of abnormal brain development and, hence, of
      intellectual disability in Down's syndrome. This defect is worsened by dendritic
      hypotrophy and connectivity alterations. Most of the pharmacotherapies designed
      to improve cognitive performance in Down's syndrome have been attempted in Down's
      syndrome mouse models during adult life stages. Yet, as neurogenesis is mainly a
      prenatal event, treatments aimed at correcting neurogenesis failure in Down's
      syndrome should be administered during pregnancy. Correction of neurogenesis
      during the very first stages of brain formation may, in turn, rescue improper
      brain wiring. The aim of our study was to establish whether it is possible to
      rescue the neurodevelopmental alterations that characterize the trisomic brain
      with a prenatal pharmacotherapy with fluoxetine, a drug that is able to restore
      post-natal hippocampal neurogenesis in the Ts65Dn mouse model of Down's syndrome.
      Pregnant Ts65Dn females were treated with fluoxetine from embryonic Day 10 until
      delivery. On post-natal Day 2 the pups received an injection of 5-bromo-2
      deoxyuridine and were sacrificed after either 2 h or after 43 days (at the age of
      45 days). Untreated 2-day-old Ts65Dn mice exhibited a severe neurogenesis
      reduction and hypocellularity throughout the forebrain (subventricular zone,
      subgranular zone, neocortex, striatum, thalamus and hypothalamus), midbrain
      (mesencephalon) and hindbrain (cerebellum and pons). In embryonically treated 2
      day-old Ts65Dn mice, precursor proliferation and cellularity were fully restored
      throughout all brain regions. The recovery of proliferation potency and
      cellularity was still present in treated Ts65Dn 45-day-old mice. Moreover,
      embryonic treatment restored dendritic development, cortical and hippocampal
      synapse development and brain volume. Importantly, these effects were accompanied
      by recovery of behavioural performance. The cognitive deficits caused by Down's
      syndrome have long been considered irreversible. The current study provides novel
      evidence that a pharmacotherapy with fluoxetine during embryonic development is
      able to fully rescue the abnormal brain development and behavioural deficits that
      are typical of Down's syndrome. If the positive effects of fluoxetine on the
      brain of a mouse model are replicated in foetuses with Down's syndrome,
      fluoxetine, a drug usable in humans, may represent a breakthrough for the therapy
      of intellectual disability in Down's syndrome. 

PMID- 24334315
TI  - A high resolution SPECT detector based on thin continuous LYSO.
AB  - Single-photon emission computed tomography (SPECT) detectors with improved
      spatial resolution can be used to build multi-pinhole SPECT systems that have a
      higher sensitivity or a higher spatial resolution. In order to improve the
      spatial resolution we investigate the performance of a 2 mm thick continuous
      Lutetium Yttrium Orthosilicate (LYSO) scintillator and compare it to the
      performance of a 5 mm thick continuous NaI(Tl) scintillator. The advantages of
      LYSO are its high stopping power and its non-hygroscopicity. Drawbacks are the
      lower light output and the intrinsic radioactivity. The hypothesis of this study
      is that such a thin LYSO scintillator will have a small light spread and, as a
      consequence, will also have an improved spatial resolution when coupled to a
      Hamamatsu H8500 position sensitive photomultiplier tube. To optimize the spatial
      resolution and the useful detector area we used a mean nearest neighbor event
      positioning method. Beam source measurements ((99m)Tc, 140 keV) were done to
      investigate the energy resolution and the spatial resolution of both detectors.
      The effect of the intrinsic radioactivity of the LYSO scintillator in the energy
      window was quantified. The mean energy resolution is 9.3% for the NaI(Tl)
      scintillator and 21.3% for the LYSO scintillator. The LYSO spectrum shows an X
      ray escape peak which decreases the detection efficiency with 9.1%. The spatial
      resolution of the LYSO detector (0.93 mm full width at half maximum (FWHM)) is
      superior to the spatial resolution of the NaI(Tl) detector (1.37 mm FWHM). The
      intrinsic radioactivity in the energy window (42% window centered at 140 keV) is
      low (125.6 cps, 0.024 cps mm(-3)). LYSO is a promising scintillator for small
      animal SPECT imaging, where spatial resolution is more important than energy
      resolution. 

PMID- 24334314
TI  - Combined insular and striatal dopamine dysfunction are associated with executive
      deficits in Parkinson's disease with mild cognitive impairment.
AB  - The ability to dynamically use various aspects of cognition is essential to daily
      function, and reliant on dopaminergic transmission in cortico-striatal circuitry.
      Our aim was to investigate both striatal and cortical dopaminergic changes in
      patients with Parkinson's disease with mild cognitive impairment, who represent a
      vulnerable group for the development of dementia. We hypothesized severe striatal
      dopamine denervation in the associative (i.e. cognitive) region and cortical D2
      receptor abnormalities in the salience and executive networks in Parkinson's
      disease with mild cognitive impairment compared with cognitively normal patients
      with Parkinson's disease and healthy control subjects. We used positron emission
      tomography imaging with dopaminergic ligands (11)C-dihydrotetrabenazine, to
      investigate striatal dopamine neuron integrity in the associative subdivision and
      (11)C-FLB 457, to investigate cortical D2 receptor availability in patients with
      Parkinson's disease (55-80 years of age) with mild cognitive impairment (n = 11),
      cognitively normal patients with Parkinson's disease (n = 11) and age-matched
      healthy control subjects (n = 14). Subjects were administered a
      neuropsychological test battery to assess cognitive status and determine the
      relationship between dopaminergic changes and cognitive performance. We found
      that patients with mild cognitive impairment had severe striatal dopamine
      depletion in the associative (i.e. cognitive) subdivision as well as reduced D2
      receptor availability in the bilateral insula, a key cognitive hub, compared to
      cognitively normal patients and healthy subjects after controlling for age,
      disease severity and daily dopaminergic medication intake. Associative striatal
      dopamine depletion was predictive of D2 receptor loss in the insula of patients
      with Parkinson's disease with mild cognitive impairment, demonstrating
      interrelated striatal and cortical changes. Insular D2 levels also predicted
      executive abilities in these patients as measured using a composite executive z
      score obtained from neuropsychological testing. Furthermore we assessed cortical
      thickness to ensure that D2 receptor changes were not confounded by brain
      atrophy. There was no difference between groups in cortical thickness in the
      insula, or any other cortical region of interest. These findings suggest that
      striatal dopamine denervation combined with insular D2 receptor loss underlie
      mild cognitive impairment in Parkinson's disease and in particular decline in
      executive function. Furthermore, these findings suggest a crucial and direct role
      for dopaminergic modulation in the insula in facilitating cognitive function. 

PMID- 24334316
TI  - Subliminal priming of intentional inhibition.
AB  - Intentional choice is an important process underlying human behaviour.
      Intentional inhibition refers to the capacity to endogenously cancel an about-to
      be-executed action at the last moment. Previous research suggested that such
      intentional inhibitory control requires conscious effort and awareness. Here we
      show that intentional decisions to inhibit are nevertheless influenced by
      unconscious processing. In a novel version of the Go/No-Go task, participants
      made speeded keypress actions to a Go target, or withheld responses to a No-Go
      target, or made free, spontaneous choices whether to execute or inhibit a
      keypress when presented with a free-choice target. Prior to each target,
      subliminal masked prime arrows were presented. Primes could be congruent with the
      Go or No-Go arrows, or neutral. Response times and proportion of action choices
      were measured. Primes were presented at latencies that would give either positive
      or negative compatibility effects (PCE, Experiment 1, and NCE, Experiment 2,
      respectively), based on previous literature. Go-primes at positive-compatibility
      latencies facilitated speeded response times as expected, but did not influence
      number of choices to act on free-choice trials. However, when Go primes were
      presented at negative-compatibility latencies, "free" decisions to inhibit were
      significantly increased. Decisions to act or not can be unconsciously
      manipulated, at least by inhibitory mechanisms. The cognitive mechanisms for
      intentionally withholding an action can be influenced by unconscious processing.
      We discuss possible moral and legal implications of these findings. 

PMID- 24334317
TI  - Champ or chump? Challenge and threat states during pressurized competition.
AB  - The present research examined the immediate impact of challenge and threat states
      on golf performance in both real competition and a laboratory-based task. In
      Study 1, 199 experienced golfers reported their evaluations of competition
      demands and personal coping resources before a golf competition. Evaluating the
      competition as a challenge (i.e., sufficient resources to cope with demands) was
      associated with superior performance. In Study 2, 60 experienced golfers randomly
      received challenge or threat manipulation instructions and then performed a
      competitive golf-putting task. Challenge and threat states were successfully
      manipulated and the challenge group outperformed the threat group. Furthermore,
      the challenge group reported less anxiety, more facilitative interpretations of
      anxiety, less conscious processing, and displayed longer quiet eye durations.
      However, these variables failed to mediate the group-performance relationship.
      These studies demonstrate the importance of considering preperformance
      psychophysiological states when examining the influence of competitive pressure
      on motor performance. 

PMID- 24334318
TI  - The motivational effects of social contagion on exercise participation in young
      female adults.
AB  - Young inactive healthy-weight females (n = 42) were randomly assigned to exercise
      at a self-selected pace on a treadmill beside a confederate who was providing
      either intrinsic or externally regulated verbal primes. Heart rate (HR), rating
      of perceived exertion (RPE), percentage of time spent in moderate-to-vigorous
      physical activity (MVPA), and exercise continuance were recorded. Participants
      completed a self-report questionnaire assessing mood pre- and postexercise
      session and postexercise motivational outcomes. The intrinsic motivation group
      reported higher RPE values after 8 min of exercise, had higher recorded HR
      measures at all 5 recorded time points, exercised at a higher %HR max, spent more
      time in MVPA, and were more likely to continue to exercise than participants in
      the externally regulated motivation group. A time effect was noted for vigor.
      Based on these findings, exercise motivation can be "contagious" through verbal
      primes, suggesting that exercising with or around intrinsically motivated
      individuals may have beneficial outcomes. 

PMID- 24334319
TI  - Experts in offside decision making learn to compensate for their illusory
      perceptions.
AB  - In association football, the flash-lag effect appears to be a viable explanation
      for erroneous offside decision making. Due to this spatiotemporal illusion,
      assistant referees (ARs) perceive the player who receives the ball ahead of his
      real position. In this experiment, a laboratory decision-making task was used to
      demonstrate that international top-class ARs, compared with amateur soccer
      players, do not have superior perceptual sensitivity. They clearly modify their
      decision criterion according to the contextual needs and, therefore, show a
      higher response bias toward not responding to the stimulus, in particular in the
      most difficult situations. Thus, international ARs show evidence for response
      level compensation, resulting in a specific cost (i.e., more misses), which
      clearly reflects the use of particular (cognitive) strategies. In summary, it
      appears that experts in offside decision making can be distinguished from novices
      more on the cognitive or decision-making level than on the perceptual level. 

PMID- 24334320
TI  - The influence of referees' expertise, gender, motivation, and time constraints on
      decisional bias against women.
AB  - The influence of player gender on referees' decision making was experimentally
      investigated. In Experiment 1, including 145 male handball referees, we
      investigated (a) the influence of referees' level of expertise on their
      decisional biases against women and (b) the referees' gender stereotypes. Results
      revealed that biases against women were powerful regardless of the referees'
      level of expertise and that male referees' stereotype toward female players tends
      to be negative. In Experiment 2, including 115 sport science students, we
      examined the influence of the participants' gender, motivation to control bias,
      and time constraints on gender bias. Results indicated that participants' gender
      had no impact on gender bias and that participants were able to reduce this bias
      in conditions in which they were motivated to control the bias. 

PMID- 24334321
TI  - A cluster analysis of affective states before and during competition.
AB  - The purposes of the current study were to identify affective profiles of athletes
      both before and during the competition and to examine differences between these
      profiles on coping and attainment of sport goals among a sample of 306 athletes.
      The results of hierarchical (Ward's method) and nonhierarchical (k means) cluster
      analyses revealed four different clusters both before and during the competition.
      The four clusters were very similar at the two measurement occasions: high
      positive affect facilitators (n = 88 and 81), facilitators (n = 75 and 25), low
      affect debilitators (n = 83 and 127), and high negative affect debilitators (n =
      60 and 73). Results of MANOVAs revealed that coping and attainment of sport
      achievement goal significantly differed across the affective profiles. Results
      are discussed in terms of current research on positive and negative affective
      states. 

PMID- 24334322
TI  - Feelings of energy, exercise-related self-efficacy, and voluntary exercise
      participation.
AB  - This study used a path analysis approach to examine the relationship between
      feelings of energy, exercise-related self-efficacy beliefs, and exercise
      participation. A cross-sectional mailing survey design was used to measure
      feelings of physical and mental energy, task and scheduling self-efficacy
      beliefs, and voluntary moderate and vigorous exercise participation in 368
      healthy, full-time undergraduate students (mean age = 21.43 +/- 2.32 years). The
      path analysis revealed that the hypothesized path model had a strong fit to the
      study data. The path model showed that feelings of physical energy had
      significant direct effects on task and scheduling self-efficacy beliefs as well
      as exercise behaviors. In addition, scheduling self-efficacy had direct effects
      on moderate and vigorous exercise participation. However, there was no
      significant direct relationship between task self-efficacy and exercise
      participation. The path model also revealed that scheduling self-efficacy
      partially mediated the relationship between feelings of physical energy and
      exercise participation. 

PMID- 24334323
TI  - Moderating influence of dominant attentional style and exercise intensity on
      responses to asynchronous music.
AB  - We examined independent and combined influences of asynchronous music and
      dominant attentional style (DAS) on psychological and psychophysical variables
      during exercise using mixed methods. Participants (N = 34) were grouped according
      to DAS and completed treadmill runs at three intensities (low, moderate, high)
      crossed with three music conditions (motivational, oudeterous, no-music control).
      State attentional focus shifted from dissociative to associative with increasing
      intensity and was most aligned with DAS during moderate-intensity exercise. Both
      music conditions facilitated dissociation at low-to-moderate intensities. At high
      exercise intensity, both music conditions were associated with reduced RPE among
      participants with an associative DAS. Dissociators reported higher RPE overall
      during moderate and high intensities. Psychological responses were most positive
      in the motivational condition, followed by oudeterous and control. Findings
      illustrate the relevance of individual differences in DAS as well as task
      intensity and duration when selecting music for exercise. 

PMID- 24334324
TI  - The integrated model of sport confidence: a canonical correlation and mediational
      analysis.
AB  - The main purpose of the study was to examine crucial parts of Vealey's (2001)
      integrated framework hypothesizing that sport confidence is a mediating variable
      between sources of sport confidence (including achievement, self-regulation, and
      social climate) and athletes' affect in competition. The sample consisted of 386
      athletes, who completed the Sources of Sport Confidence Questionnaire, Trait
      Sport Confidence Inventory, and Dispositional Flow Scale-2. Canonical correlation
      analysis revealed a confidence-achievement dimension underlying flow. Bias
      corrected bootstrap confidence intervals in AMOS 20.0 were used in examining
      mediation effects between source domains and dispositional flow. Results showed
      that sport confidence partially mediated the relationship between achievement and
      self-regulation domains and flow, whereas no significant mediation was found for
      social climate. On a subscale level, full mediation models emerged for
      achievement and flow dimensions of challenge-skills balance, clear goals, and
      concentration on the task at hand. 

PMID- 24334325
TI  - The role of body awareness and mindfulness in the relationship between exercise
      and eating behavior.
AB  - This study examined the potential mediating roles of mindfulness and body
      awareness in the relationship between exercise and eating behavior. Female
      exercisers (N = 159) recruited from fitness centers, yoga centers, and the
      community completed a questionnaire incorporating measures of exercise behavior,
      body awareness, trait mindfulness, mindful eating, dietary intake, and disordered
      eating symptoms. Participation in yoga was associated with significantly lower
      disordered eating (mediated by body awareness), whereas the amount of time spent
      participating in cardio-based exercise was associated with greater eating
      disturbance. The relationships between amount of exercise and actual food intake
      were not mediated by trait mindfulness or body awareness. The differential
      findings for dietary intake and disordered eating indicate that the body
      awareness cultivated in different forms of exercise may be more beneficial for
      clinical populations or those at risk for eating disorders than for modifying
      actual dietary intake in the general population. 

PMID- 24334327
TI  - Applications of inorganic nanoparticles as therapeutic agents.
AB  - During the last decade, various functional nanostructured materials with
      interesting optical, magnetic, mechanical and chemical properties have been
      extensively applied to biomedical areas including imaging, diagnosis and therapy.
      In therapeutics, most research has focused on the application of nanoparticles as
      potential delivery vehicles for drugs and genes, because nanoparticles in the
      size range of 2-100 nm can interact with biological systems at the molecular
      level, and allow targeted delivery and passage through biological barriers.
      Recent investigations have even revealed that several kinds of nanomaterials are
      intrinsically therapeutic. Not only can they passively interact with cells, but
      they can also actively mediate molecular processes to regulate cell functions.
      This can be seen in the treatment of cancer via anti-angiogenic mechanisms as
      well as the treatment of neurodegenerative diseases by effectively controlling
      oxidative stress. This review will present recent applications of inorganic
      nanoparticles as therapeutic agents in the treatment of disease.

PMID- 24334328
TI  - Direct dose mapping versus energy/mass transfer mapping for 4D dose accumulation:
      fundamental differences and dosimetric consequences.
AB  - The direct dose mapping (DDM) and energy/mass transfer (EMT) mapping are two
      essential algorithms for accumulating the dose from different anatomic phases to
      the reference phase when there is organ motion or tumor/tissue deformation during
      the delivery of radiation therapy. DDM is based on interpolation of the dose
      values from one dose grid to another and thus lacks rigor in defining the dose
      when there are multiple dose values mapped to one dose voxel in the reference
      phase due to tissue/tumor deformation. On the other hand, EMT counts the total
      energy and mass transferred to each voxel in the reference phase and calculates
      the dose by dividing the energy by mass. Therefore it is based on fundamentally
      sound physics principles. In this study, we implemented the two algorithms and
      integrated them within the Eclipse treatment planning system. We then compared
      the clinical dosimetric difference between the two algorithms for ten lung cancer
      patients receiving stereotactic radiosurgery treatment, by accumulating the
      delivered dose to the end-of-exhale (EE) phase. Specifically, the respiratory
      period was divided into ten phases and the dose to each phase was calculated and
      mapped to the EE phase and then accumulated. The displacement vector field
      generated by Demons-based registration of the source and reference images was
      used to transfer the dose and energy. The DDM and EMT algorithms produced
      noticeably different cumulative dose in the regions with sharp mass density
      variations and/or high dose gradients. For the planning target volume (PTV) and
      internal target volume (ITV) minimum dose, the difference was up to 11% and 4%
      respectively. This suggests that DDM might not be adequate for obtaining an
      accurate dose distribution of the cumulative plan, instead, EMT should be
      considered. 

PMID- 24334329
TI  - Attitudes of prehospital emergency care professionals toward refusal of
      treatment: A regional survey in Turkey.
AB  - INTRODUCTION: Prehospital emergency medicine is a specific field of emergency
      medicine. The basic approach of prehospital emergency medicine is to provide
      patients with medical intervention at the scene of the incident. This special
      environment causes health professionals to encounter various problems. One of the
      most important problems in this field is ethics, in particular questions
      involving refusal of treatment and the processes associated with it. OBJECTIVE:
      The objective of this study is to identify emergency health professionals' views
      regarding refusal of treatment. METHODS: This study was conducted with 356 health
      professionals who were on active duty in prehospital emergency health services.
      The data were collected through a form which included 10 statements. The
      participants were asked to indicate their level of agreement with the statements
      given by rating them between 0 and 10. ETHICAL CONSIDERATIONS: Before conducting
      the research, permission was received from the local ethics committee.
      Participants were given written information about the purpose of the study.
      Participants were assured that their participation was voluntary. RESULTS: The
      healthcare professionals with fewer years of experience in the profession and
      female participants adopted an attitude of giving priority to providing care.
      Young participants, in general, respected patient autonomy. However,
      paradoxically, when it comes to emergency medical cases, they expressed an
      opinion closer to paternalism. CONCLUSIONS: This study has found that prehospital
      emergency health professionals generally respect the patient's right to refuse
      treatment; however, they do not prioritize this right when there is a life
      threatening situation or when the person does not have decision-making capacity.
      In these cases, prehospital emergency health professionals tended to adopt a more
      paternalistic approach.

PMID- 24334331
TI  - The administrative costs of community-based health insurance: a case study of the
      community health fund in Tanzania.
AB  - Community-based health insurance expansion has been proposed as a financing
      solution for the sizable informal sector in low-income settings. However, there
      is limited evidence of the administrative costs of such schemes. We assessed
      annual facility and district-level costs of running the Community Health Fund
      (CHF), a voluntary health insurance scheme for the informal sector in a rural and
      an urban district from the same region in Tanzania. Information on resource use,
      CHF membership and revenue was obtained from district managers and health workers
      from two facilities in each district. The administrative cost per CHF member
      household and the cost to revenue ratio were estimated. Revenue collection was
      the most costly activity at facility level (78% of total costs), followed by
      stewardship and management (13%) and pooling of funds (10%). Stewardship and
      management was the main activity at district level. The administration cost per
      CHF member household ranged from USD 3.33 to USD 12.12 per year. The cost to
      revenue ratio ranged from 50% to 364%. The cost of administering the CHF was high
      relative to revenue generated. Similar studies from other settings should be
      encouraged. 

PMID- 24334332
TI  - Enrichment of human osteosarcoma stem cells based on hTERT transcriptional
      activity.
AB  - Telomerase is crucial for the maintenance of stem/progenitor cells in adult
      tissues and is detected in most malignant cancers, including osteosarcoma.
      However, the relationship between telomerase expression and cancer stem cells
      remains unknown. We observed that sphere-derived osteosarcoma cells had higher
      telomerase activity, indicating that telomerase activity might be enriched in
      osteosarcoma stem cells. We sorted subpopulations with high or low telomerase
      activity (TEL) using hTERT transcriptional promoter-induced green fluorescent
      protein (GFP). The TELpos cells showed an increased sphere and tumor propagating
      capacity compared to TELneg cells, and enhanced stem cell-like properties such as
      invasiveness, metastatic activity and resistance to chemotherapeutic agents both
      in vitro and in vivo. Furthermore, the telomerase inhibitor MST312 prevented
      tumorigenic potential both in vitro and in vivo, preferentially targeting the
      TELpos cells. These data support telomerase inhibition as a potential targeted
      therapy for osteosarcoma stem-like cells. 

PMID- 24334333
TI  - Fabrics coated with lubricated nanostructures display robust omniphobicity.
AB  - The development of a stain-resistant and pressure-stable textile is desirable for
      consumer and industrial applications alike, yet it remains a challenge that
      current technologies have been unable to fully address. Traditional
      superhydrophobic surfaces, inspired by the lotus plant, are characterized by two
      main components: hydrophobic chemical functionalization and surface roughness.
      While this approach produces water-resistant surfaces, these materials have
      critical weaknesses that hinder their practical utility, in particular as robust
      stain-free fabrics. For example, traditional superhydrophobic surfaces fail
      (i.e., become stained) when exposed to low-surface-tension liquids, under
      pressure when impacted by a high-velocity stream of water (e.g., rain), and when
      exposed to physical forces such as abrasion and twisting. We have recently
      introduced slippery lubricant-infused porous surfaces (SLIPS), a self-healing,
      pressure-tolerant and omniphobic surface, to address these issues. Herein we
      present the rational design and optimization of nanostructured lubricant-infused
      fabrics and demonstrate markedly improved performance over traditional
      superhydrophobic textile treatments: SLIPS-functionalized cotton and polyester
      fabrics exhibit decreased contact angle hysteresis and sliding angles, omni
      repellent properties against various fluids including polar and nonpolar liquids,
      pressure tolerance and mechanical robustness, all of which are not readily
      achievable with the state-of-the-art superhydrophobic coatings. 

PMID- 24334334
TI  - Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular
      dystrophy: targeting the renin-angiotensin system.
AB  - New Findings What is the topic of this review? This symposium report summarizes
      autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-delta
      deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with
      emphasis on the roles of autonomic dysregulation and activation of the renin
      angiotensin system at a young age. What advances does it highlight? The
      contributions of the autonomic nervous system and the renin-angiotensin system to
      the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that
      autonomic dysregulation precedes and predicts later development of cardiac
      dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the
      angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7)
      abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and
      increases spontaneous locomotor activity. Muscular dystrophies are a
      heterogeneous group of genetic muscle diseases characterized by muscle weakness
      and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin
      glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in
      animals and humans. Aberrant autonomic signalling is recognized in a variety of
      neuromuscular disorders. We hypothesized that activation of the renin-angiotensin
      system contributes to skeletal muscle and autonomic dysfunction in mice deficient
      in the sarcoglycan-delta (Sgcd) gene at a young age and that this early autonomic
      dysfunction contributes to the later development of left ventricular (LV)
      dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice
      exhibit histopathological features of skeletal muscle dystrophy, decreased
      locomotor activity and severe autonomic dysregulation, but normal LV function.
      Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was
      accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic
      dysregulation at a young age predicted later development of LV dysfunction and
      higher mortality in Sgcd-/- mice. Treatment of Sgcd-/- mice with the angiotensin
      type 1 receptor blocker losartan for 8-9 weeks, beginning at 3 weeks of age,
      decreased fibrosis and oxidative stress in skeletal muscle, increased locomotor
      activity and prevented autonomic dysfunction. Chronic infusion of the counter
      regulatory peptide angiotensin-(1-7) resulted in similar protection. We conclude
      that activation of the renin-angiotensin system, at a young age, contributes to
      skeletal muscle and autonomic dysfunction in muscular dystrophy. We speculate
      that the latter is mediated via abnormal sensory nerve and/or cytokine signalling
      from dystrophic skeletal muscle to the brain and contributes to age-related LV
      dysfunction, dilated cardiomyopathy, arrhythmias and premature death. Therefore,
      correcting the early autonomic dysregulation and renin-angiotensin system
      activation may provide a novel therapeutic approach in muscular dystrophy.

PMID- 24334335
TI  - Elevated levels of branched-chain amino acids have little effect on pancreatic
      islet cells, but L-arginine impairs function through activation of the
      endoplasmic reticulum stress response.
AB  - Recent metabolic profiling studies have identified a correlation between branched
      chain amino acid levels, insulin resistance associated with prediabetes and
      susceptibility to type 2 diabetes. Glucose and lipids in chronic excess have been
      reported to induce toxic effects in pancreatic beta-cells, but the effect of
      elevated amino acid concentrations on primary islet cell function has not been
      investigated to date. The aim of this study was to investigate the effect of
      chronic exposure to various amino acids on islet cell function in vitro. Isolated
      rat islets were incubated over periods of 48 h with a range of concentrations of
      individual amino acids (0.1 MUm to 10 mm). After 48 h, islets were assessed for
      glucose-dependent insulin secretion capacity, proliferation or islet cell
      apoptosis. We report that elevated levels of branched-chain amino acids have
      little effect on pancreatic islet cell function or viability; however, increased
      levels of the amino acid l-arginine were found to be beta-cell toxic, causing a
      dose-dependent decrease in insulin secretion accompanied by a decrease in islet
      cell proliferation and an increase in islet cell apoptosis. These effects were
      not due to l-arginine-dependent increases in production of nitric oxide but arose
      through elicitation of the islet cell endoplasmic reticulum stress response. This
      novel finding indicates, for the first time, that the l-arginine concentration in
      vitro may impact negatively on islet cell function, thus indicating further
      complexity in relationship to in vivo susceptibility of beta-cells to nutrient
      induced dysfunction. 

PMID- 24334336
TI  - Bronchial thermoplasty: interventional therapy in asthma.
AB  - Bronchial thermoplasty is a new treatment option for patients with severe
      bronchial asthma who remain symptomatic despite maximal medical therapy. The aim
      of this interventional therapy option is the reduction of smooth muscle in the
      central and peripheral airways in order to reduce symptomatic bronchoconstriction
      via the application of heat. A full treatment with bronchial thermoplasty is
      divided into three bronchoscopies. Randomized, controlled clinical trials have
      shown an increase in quality of life, a reduction in severe exacerbations, and
      decreases in emergency department visits as well as days lost from school or
      work. The trials did not show a reduction in hyperresponsiveness or improvement
      in forced expiratory volume in 1 s. Short-term adverse effects include an
      increase in exacerbation rate, an increase in respiratory infections and an
      increase in hospitalizations. In the 5-year follow up of the studies available
      there was evidence of clinical and functional stability of the treated patients.
      Further studies are necessary to identify an asthma phenotype that responds well
      to this treatment. 

PMID- 24334337
TI  - Development of levofloxacin inhalation solution to treat Pseudomonas aeruginosa
      in patients with cystic fibrosis.
AB  - Inhaled therapies allow for the targeted delivery of antimicrobials directly into
      the lungs and have been widely used in the treatment of cystic fibrosis (CF)
      acute pulmonary exacerbations. Nebulized levofloxacin solution (MP-376) is a
      novel therapy that is currently being evaluated in phase I, II, and III clinical
      trials among patients with stable CF and recent isolation of Pseudomonas
      aeruginosa from sputum. Phase I studies have investigated the single and multiple
      dose pharmacokinetics of MP-376 and shown that it is rapidly absorbed from the
      lungs and results in low systemic concentrations. A subsequent phase IB study
      found that MP-376 pharmacokinetics were comparable among adults and children 6-16
      years of age. Further phase II studies reported that sputum P. aeruginosa density
      decreased in a dose-dependent manner among patients who were randomized to MP-376
      when compared with patients who received placebo. Improvements in pulmonary
      function and a decrease in the need for other antipseudomonal antibiotics were
      also reported for patients who received inhaled levofloxacin. The most common
      adverse event was dysgeusia (abnormal taste sensation), which was reported by
      nearly half of the participants who received MP-376. No serious drug-related
      adverse events were reported. These findings are encouraging; however, data from
      the two ongoing phase III trials are needed to determine whether MP-376
      demonstrates substantial evidence of safety and efficacy as a chronic CF
      maintenance therapy and therefore may be useful in routine clinical practice. 

PMID- 24334338
TI  - Comparison of outcomes following stereotactic body radiotherapy for non-small
      cell lung cancer in patients with and without pathological confirmation.
AB  - PURPOSE/OBJECTIVE: Treatment of presumed early-stage lung cancer with definitive
      radiation therapy in the absence of a pathologically confirmed specimen
      frequently occurs. However, it is not well described in the literature, and there
      are few North American series reporting on this patient population. We report
      outcomes in patients treated with stereotactic body radiotherapy (SBRT) for
      presumed lung cancer and compare them to outcomes in patients treated with SBRT
      with pathologically confirmed non-small cell lung cancer (NSCLC).
      MATERIALS/METHODS: This study is based on a retrospective review of 55 patients
      with presumed or confirmed lung cancer: 23 patients had nondiagnostic or absent
      pathologic specimens while 32 patients had pathologically confirmed NSCLC. All
      patients had hypermetabolic primary lesions on a positron emission tomography
      (PET) or PET/computed tomography (CT) scan. SBRT was delivered as 48-56 Gy in
      four to five fractions via a four-dimensional CT treatment plan. RESULTS: Of the
      patients without pathological confirmation, the mean age was 78 (range 63-89
      years) and 17 (74%) were men. The mean tumor size was 2.5 cm (range 1.0-5.1).
      Reasons for not having confirmed pathologic diagnosis included indeterminate
      biopsy specimen or an inability to tolerate a biopsy procedure due to poor
      respiratory status. SBRT was chosen due to noncandidacy for surgery in 17
      patients (74%) or patient refusal of surgery in six (26%). Median follow up was
      24.2 months (range 1.9-64.6): 2 of the 23 patients (8.7%) had local failure at
      the site of SBRT and 3 (13%) had regional failure. The actuarial 12-month overall
      survival was 83%. The median overall survival was 30.2 months. At last follow up,
      12 patients (52%) were alive up to 64.6 months after treatment. SBRT was
      tolerated well in this series. Acute toxicity was noted in two patients (8.7%)
      and chronic toxicity in three (13%). These patient characteristics and results
      were shown to be similar to the 32 patients with pathologically confirmed NSCLC.
      On Kaplan-Meier analysis, there was no significant difference (p = 0.27) in
      overall survival between patients with pathologically confirmed NSCLC and those
      with presumed lung cancer (which was deemed most likely NSCLC). CONCLUSION: While
      biopsy confirmation remains a goal in the workup of suspected NSCLC, SBRT without
      pathologic confirmation may represent a safe and effective option for the
      treatment of presumed NSCLC among patients who cannot tolerate or refuse surgery.

PMID- 24334339
TI  - NICE clinical guideline: antibiotics for the prevention and treatment of early
      onset neonatal infection.

PMID- 24334340
TI  - How to use... blood cultures.
AB  - Positive blood culture is the gold standard for diagnosing bacteraemia and
      fungaemia, yet there is significant variability in aspects of performing and
      interpreting the test in children and neonates. Processing a blood culture can
      take several days, and includes use of semi-automated incubation with growth
      detection and a broad range of laboratory techniques such as Gram staining,
      phenotypic or molecular identification and antimicrobial susceptibility testing
      on a cultured isolate. Sensitivity and specificity of a blood culture and time-to
      positivity depend on a number of factors related to host/pathogen interaction,
      collection and transport of the specimen to the laboratory and methods employed
      to process the specimen. Interpretation of a positive result relies on
      correlation of the identity of the cultured microorganism with the clinical
      assessment of the child. 

PMID- 24334342
TI  - Parallel nanoimaging and nanolithography using a heated microcantilever array.
AB  - We report parallel topographic imaging and nanolithography using heated
      microcantilever arrays integrated into a commercial atomic force microscope
      (AFM). The array has five AFM cantilevers, each of which has an internal
      resistive heater. The temperatures of the cantilever heaters can be monitored and
      controlled independently and in parallel. We perform parallel AFM imaging of a
      region of size 550 MUm * 90 MUm, where the cantilever heat flow signals provide a
      measure of the nanometer-scale substrate topography. At a cantilever scan speed
      of 1134 MUm s(-1), we acquire a 3.1 million-pixel image in 62 s with noise
      limited vertical resolution of 0.6 nm and pixels of size 351 nm * 45 nm. At a
      scan speed of 4030 MUm s(-1) we acquire a 26.4 million pixel image in 124 s with
      vertical resolution of 5.4 nm and pixels of size 44 nm * 43 nm. Finally, we
      demonstrate parallel nanolithography with the cantilever array, including
      iterations of measure-write-measure nanofabrication, with each cantilever
      operating independently.

PMID- 24334343
TI  - Is prepregnancy obesity associated with risk of cerebral palsy and epilepsy in
      children?
AB  - We conducted a retrospective cohort study to investigate the association between
      prepregnancy obesity in women and risk of cerebral palsy and epilepsy in their
      children using data from the South Carolina Medicaid program. The cohort included
      83,901 maternal-child pairs; 100 cases of cerebral palsy were initially
      identified, followed by 53 cases that had at least 2 cerebral palsy diagnoses.
      For confirmed epilepsy, diagnosed on at least 5 occasions or by more than 1
      provider, 83,472 observations were included with 338 cases. There was no
      association between maternal body mass index and risk of childhood epilepsy. A
      significant association between increasing maternal body mass index and any
      diagnosis of cerebral palsy was found, and morbid obesity was associated with
      increased risk of any and confirmed cerebral palsy. In conclusion, there appears
      to be an association of maternal body mass index with cerebral palsy, but there
      is no evidence to support an association with epilepsy. 

PMID- 24334344
TI  - Lower incidence of seizure among neonates treated with therapeutic hypothermia.
AB  - Animal studies suggest that hypothermia decreases seizure burden, whereas limited
      human data are inconclusive. This retrospective cohort study examines the
      relationship between therapeutic hypothermia and seizure in neonates with hypoxic
      ischemic encephalopathy. Our center admitted 224 neonates from July 2004 to
      December 2011 who met institutional cooling criteria. Seventy-three neonates were
      born during the pre-cooling era, prior to November 2007, and 151 were born during
      the cooling era. Among neonates with moderate encephalopathy, the incidence of
      seizure in cooled infants was less than half the incidence in those not cooled
      (26% cooling, 61% pre-cooling era; risk ratio = 0.43, 95% confidence interval =
      0.30-0.61). Among neonates with severe encephalopathy, there was no difference in
      the incidence (83% vs. 87%; risk ratio = 1.05, 95% confidence interval = 0.78
      1.39). These results support animal data and suggest a mechanism by which
      neonates with moderate encephalopathy can benefit more from cooling than neonates
      with severe encephalopathy.

PMID- 24334345
TI  - Acute psychosis in propionic acidemia: 2 case reports.
AB  - Propionic acidemia is an inborn deficiency of propionyl-coenzyme A (CoA)
      carboxylase activity, which leads to mitochondrial accumulation of propionyl-CoA
      and its by-products. Neurologic complications are frequent, but only a few cases
      presenting with psychiatric symptoms have been reported so far. We report 2 cases
      of children with chronic psychiatric symptoms who presented with an acute
      psychotic episode as teenagers. Both patients had hallucinations, panic and
      grossly disorganized behavior, for several weeks to several months. They had
      signs of moderate metabolic decompensation at the beginning of the episode,
      although the psychiatric symptoms lasted longer than the metabolic imbalance. We
      propose that these episodes were at least partially imputable to propionic
      acidemia. Such episodes require psychiatric examination and antipsychotic
      treatment, which may have to be adapted in case of cardiomyopathy or long QT
      syndrome. 

PMID- 24334346
TI  - A paucisymptomatic neuromuscular disease mimicking type III 5q-SMA with complex
      rearrangements in the SMN gene.
AB  - Spinal muscular atrophy is an autosomal-recessive neuromuscular disorder, causing
      progressive proximal weakness and atrophy of the voluntary muscles. More than 96%
      of the spinal muscular atrophy patients show a homozygous absence of exons 7 and
      8, or exon 7 only, in SMN1, the telomeric copy of the SMN gene. We report a young
      male patient with neurogenic symptoms and sparse muscle fiber atrophy, suggestive
      of a mild form of type III spinal muscular atrophy. He was found to be a carrier
      of intragenic mutations in both copies of the SMN gene, exhibiting a homozygous
      duplication of exons 7 and 8 in SMN1 and a homozygous deletion of exon 8 as well
      as a heterozygous deletion of exon 7 in SMN2. However, an intact full-length SMN1
      complementary deoxyribonucleic acid was identified, and SMN protein levels in a
      muscle specimen were identical to that of a healthy control, formally excluding
      the diagnosis of spinal muscular atrophy III. 

PMID- 24334347
TI  - Orienting responses to various visual stimuli in children with visual processing
      impairments or infantile nystagmus syndrome.
AB  - Quantification of orienting responses can be used to differentiate between
      children with cerebral visual impairment and infantile nystagmus syndrome. To
      further improve the sensitivity of this method, we compared orienting responses
      to a Cartoon stimulus, which contains all sorts of visual information, to stimuli
      that contain only Contrast, Form coherence, Motion coherence, Color and Motion
      detection. The stimuli were shown on an eye tracker monitor using a preferential
      looking paradigm. We found that both groups of children showed general slowing in
      orienting responses compared to controls. The children with cerebral visual
      impairment had significantly prolonged responses to Cartoon compared to the
      children with nystagmus, whereas the children with nystagmus had prolonged
      responses to Motion detection and larger fixation areas. Previously reported
      differences in orienting responses to Cartoon were replicated. Application of
      specific visual information did not alter the sensitivity of the method to
      distinguish between children with visual processing deficits. 

PMID- 24334348
TI  - Cerebral hemodynamic changes and pain perception during venipuncture: is glucose
      really effective?
AB  - Newborns are exposed to a considerable number of painful stimuli. This study is
      aimed to investigate the effects of 30% glucose solution and nonnutritive sucking
      on pain perception during venipuncture. Twenty-five term infants were randomized
      as receiving 30% dextrose (group 1) or sterile water (group 2). Neonatal Infant
      Pain Scale scores, skin conductance algesimeter recordings, and near-infrared
      spectroscopy measurements were recorded during the procedure. Neonatal Infant
      Pain Scale and skin conductance algesimeter results were decreased in both groups
      from that during venipuncture to after the procedure. Group 1 had lower Neonatal
      Infant Pain Scale scores compared with group 2 after venipuncture, different from
      the skin conductance algesimeter, where no difference was observed between
      groups. In group 1, cerebral blood volume increased after venipuncture. Glucose
      does not attenuate the Neonatal Infant Pain Scale score and skin conductance
      algesimeter index during venipuncture, but it leads to a lower Neonatal Infant
      Pain Scale score after venipuncture unlike the skin conductance algesimeter
      index, which was not lowered. 

PMID- 24334349
TI  - Ethical challenges in assisted reproduction: the place of preimplantation genetic
      diagnosis in a just society.
AB  - The purpose of this article is to provide an overview of preimplantation genetic
      diagnosis and identify the relevant moral questions it raises. In the course of
      this discussion, the scope of parental rights and the inherent difficulty in
      defining disease/disability will be considered. 

PMID- 24334350
TI  - ATTED-II in 2014: evaluation of gene coexpression in agriculturally important
      plants.
AB  - ATTED-II (http://atted.jp) is a database of coexpressed genes that was originally
      developed to identify functionally related genes in Arabidopsis and rice. Herein,
      we describe an updated version of ATTED-II, which expands this resource to
      include additional agriculturally important plants. To improve the quality of the
      coexpression data for Arabidopsis and rice, we included more gene expression data
      from microarray and RNA sequencing studies. The RNA sequencing-based coexpression
      data now cover 94% of the Arabidopsis protein-encoding genes, representing a
      substantial increase from previously available microarray-based coexpression data
      (76% coverage). We also generated coexpression data for four dicots (soybean,
      poplar, grape and alfalfa) and one monocot (maize). As both the quantity and
      quality of expression data for the non-model species are generally poorer than
      for the model species, we verified coexpression data associated with these new
      species using multiple methods. First, the overall performance of the
      coexpression data was evaluated using gene ontology annotations and the
      coincidence of a genomic feature. Secondly, the reliability of each guide gene
      was determined by comparing coexpressed gene lists between platforms. With the
      expanded and newly evaluated coexpression data, ATTED-II represents an important
      resource for identifying functionally related genes in agriculturally important
      plants. 

PMID- 24334352
TI  - Virulence of viral hemorrhagic septicemia virus (VHSV) genotypes Ia, IVa, IVb,
      and IVc in five fish species.
AB  - The susceptibility of yellow perch Perca flavescens, rainbow trout Oncorhynchus
      mykiss, Chinook salmon O. tshawytscha, koi Cyprinus carpio koi, and Pacific
      herring Clupea pallasii to 4 strains of viral hemorrhagic septicemia virus (VHSV)
      was assessed. Fish were challenged via intraperitoneal injection with high (1 *
      106 plaque-forming units, PFU) and low (1 * 103 PFU) doses of a European strain
      (genotype Ia), and North American strains from the West coast (genotype IVa),
      Great Lakes (genotype IVb), and the East coast (genotype IVc). Pacific herring
      were exposed to the same VHSV strains, but at a single dose of 5 * 103 PFU ml-1
      by immersion in static seawater. Overall, yellow perch were the most susceptible,
      with cumulative percent mortality (CPM) ranging from 84 to 100%, and 30 to 93% in
      fish injected with high or low doses of virus, respectively. Rainbow trout and
      Chinook salmon experienced higher mortalities (47 to 98% CPM) after exposure to
      strain Ia than to the other virus genotypes. Pacific herring were most
      susceptible to strain IVa with an average CPM of 80% and moderately susceptible
      (42 to 52% CPM) to the other genotypes. Koi had very low susceptibility (<=5.0%
      CPM) to all 4 VHSV strains. Fish tested at 7 d post challenge were positive for
      all virus strains, with yellow perch having the highest prevalence and
      concentrations of virus, and koi the lowest. While genotype Ia had higher
      virulence in salmonid species, there was little difference in virulence or host
      specificity between isolates from subtypes IVa, IVb, and IVc. 

PMID- 24334351
TI  - Panulirus argus virus 1 (PaV1) infection prevalence and risk factors in a Mexican
      lobster fishery employing casitas.
AB  - In Bahia de la Ascension in Mexico, the Caribbean spiny lobster Panulirus argus
      fishery is based on extensive use of artificial shelters (casitas) that can
      harbor both juveniles and adults of this highly gregarious species. There is
      concern that the use of casitas might increase contact transmission of Panulirus
      argus virus 1 (PaV1). However, a previous study found no evidence for lobster
      crowding within casitas influencing the prevalence of clinical PaV1 disease,
      although differences in clinical prevalence were noted between different bay
      environments. To investigate this more closely, 683 lobsters were sampled from
      casitas in 2 zones in this bay (Vigia Chico, a shallow low-vegetation zone, and
      Punta Allen, a deeper dense-vegetation zone) previously found to have the lowest
      and highest prevalence, respectively, of observed clinical signs. When hemolymph
      collected from these lobsters was tested by PCR, the prevalence of PaV1 infection
      was found to be significantly lower in Vigia Chico relative to Punta Allen
      irrespective of season or the size, sex, or presence of shell injuries on
      lobsters. Among 714 large commercial-catch lobsters collected throughout the bay,
      the prevalence of infection was low irrespective of year or sex. For all lobsters
      tested, the sensitivity (0.510) at which PaV1 infection was detected by observed
      clinical signs was about half that determined by PCR, but the specificity of
      clinical signs was absolute (1), indicating that a simple 2* correction factor
      can be used to accurately estimate PaV1 infection prevalence based on more easily
      conducted visual assessments of lobsters. 

PMID- 24334353
TI  - Detection of novel strains of cyprinid herpesvirus closely related to koi
      herpesvirus.
AB  - Cyprinid herpesvirus 3 (CyHV-3) or koi herpesvirus (KHV) is a devastating virus
      of carp. Using generic primers for the DNA polymerase and the major capsid
      protein genes of cyprinid herpesviruses, nucleotide sequences divergent from
      previously described CyHV-3 were obtained. At least 3 novel groups of putative
      CyHV-3-like viruses were identified, sharing 95 to 98% nucleotide identity with
      CyHV-3 strains. Carp carrying the CyHV-3 variants did not show clinical signs
      consistent with CyHV-3 infection and originated from locations with no actual
      CyHV-3 outbreaks. These strains might represent low- or non-pathogenic variants
      of CyHV-3. 

PMID- 24334354
TI  - Atlantic salmon papillomatosis in Russia and molecular characterization of the
      associated herpesvirus.
AB  - Papillomatosis of Atlantic salmon Salmo salar has been reported for decades in
      Russia, Scandinavia and Scotland. The disease is typically benign although heavy
      losses have occasionally been reported. A herpesviral etiology has been suggested
      based on ultrastructural evidence; however, the virus has not been isolated or
      genetically characterized. In this study, we provide the first viral sequences
      detected in the papillomas from diseased Russian Atlantic salmon. Phylogenetic
      analyses, based on the partial sequences of the herpesviral polymerase and
      terminase genes, supported the virus as a novel member of the genus Salmonivirus
      within the family Alloherpesviridae. The sequences of the Atlantic salmon
      papillomatosis virus differ markedly from those of the 3 known salmoniviruses;
      therefore, the authors propose the species designation Salmonid herpesvirus 4 to
      be considered for approval by the International Committee on Taxonomy of Viruses.

PMID- 24334355
TI  - Prevalence, intensity, and phylogenetic analysis of Henneguya piaractus and
      Myxobolus cf. colossomatis from farmed Piaractus mesopotamicus in Brazil.
AB  - Henneguya piaractus and Myxobolus colossomatis (Myxosporea: Myxobolidae) are
      commonly found in the characid Piaractus mesopotamicus, an important fish farm
      species in Brazil. This paper describes the prevalence, mean intensity, molecular
      phylogeny, ultrastructure, and histology of H. piaractus and M. cf. colossomatis
      found infecting specimens of P. mesopotamicus collected from fish farms in the
      state of Sao Paulo, Brazil. A total of 278 fish were collected from 3 fish farms
      between February 2008 and July 2010. Parasite prevalence and mean intensity
      varied throughout the study period, and according to location and year. A
      phylogenetic tree, placing South American species in a global context, showed a
      clear tendency among myxosporean species to cluster according to host families.
      Ultrastructural analysis for M. cf. colossomatis showed the plasmodial wall with
      numerous projections toward host cells and phagocytic activity. Histopathological
      data showed hyperplasia caused by H. piaractus in highly infected fish.
      Histological and ultrastructural analysis of H. piaractus showed results similar
      to those that have previously been reported. 

PMID- 24334356
TI  - Risk factors for cardiomyopathy syndrome (CMS) in Norwegian salmon farming.
AB  - Cardiomyopathy syndrome (CMS) has been an economically important disease in
      Norwegian aquaculture since the 1990s. In this study, data on monthly production
      characteristics and case registrations were combined in a cohort study and
      supplemented with a questionnaire-based case-control survey on management factors
      in order to identify risk factors for CMS. The cohort study included cases and
      controls from 2005 to 2012. From this dataset differences between all cases and
      controls were analyzed by a mixed effect multivariate logistic regression. From
      this we found that the probability of CMS increased with increasing time in the
      sea, infection pressure, and cohort size, and that cohorts which had previously
      been diagnosed with heart and skeletal muscle inflammation or which were in farms
      with a history of CMS in previous cohorts had double the odds of developing CMS.
      The model was then used to calculate the predicted value for each cohort from
      which additional data were obtained via the questionnaire-based survey and used
      as offset for calculating the probability of CMS in a semi-univariate analysis of
      additional risk factors. Finally, the model was used to calculate the probability
      of developing CMS in 100 different scenarios in which the cohorts were subject to
      increasingly worse conditions with regards to the risk factors from the dataset.
      We believe that this exercise is a good way of communicating the findings to
      farmers, so they can make informed decisions when trying to avoid CMS in their
      fish cohorts. 

PMID- 24334357
TI  - Retroperitoneal hemangiosarcoma in a common carp Cyprinus carpio: a case report.
AB  - A 7.5 kg common carp Cyprinus carpio presented with prominent localized swelling
      in the caudal right coelomic area, identified by ultrasound as a fluid filled
      mass. Fine needle aspirate (FNA) and culture results suggested a sterile seroma.
      Centesis removed 290 ml of serosanguinous fluid that returned within days.
      Recheck ultrasonography revealed a solid component within the cavity. Radiography
      demonstrated irregular lysis and misalignment of vertebrae adjacent to the mass,
      most suggestive of bacterial osteitis or neoplasia. Treatment with antibiotics
      followed for 2 mo but failed to resolve the lesion. Repeated radiography and
      ultrasonography showed progressive enlargement of the mass, with vertebral lysis
      and invasion characteristic of neoplasia. Ultrasound-guided FNA of the solid
      component of the mass was non-diagnostic. Euthanasia was elected due to the poor
      clinical response and primary differential of neoplasia. Post-mortem MRI and CT
      confirmed a retroperitoneal soft tissue mass, partially surrounded by a fluid
      filled cavity, causing vertebral lysis and infiltration of the spinal canal.
      Expansion of the mass caused severe muscle loss and an associated elevation in
      creatine kinase (>120000 U l-1). Necropsy results corroborated the MRI and CT
      findings, revealing a retroperitoneal, multilobular, red and tan mass causing
      dorsal displacement of the vertebral column, with vertebral lysis, pathologic
      fracture and invasion of the spinal canal. Histopathologic examination revealed a
      locally aggressive neoplasm exhibiting multiple patterns of growth, including
      endothelial lined vascular channels and solid areas formed by more pleomorphic
      polygonal and spindle cells, consistent with hemangiosarcoma. 

PMID- 24334358
TI  - Microbial functional genes associated with coral health and disease.
AB  - Both the incidence and prevalence of coral disease are rapidly increasing, and as
      a consequence, many studies involving coral microbial associates have been
      conducted. However, very few of these have considered microbial functional genes.
      This is an underutilized approach for studying coral disease etiology which is
      capable of revealing the molecular processes of the coral microbial community.
      This review presents a summary of the known microbial functional genes that have
      been linked to coral health and disease. Overall functional gene diversity tended
      to be lower in healthy corals than diseased or bleached corals, and respiration
      and photosynthesis functional genes appeared to be crucial to coral health. Genes
      associated with the nitrogen cycle were the most studied, were highly represented
      within the coral holobiont, and their expression often shifted in diseased or
      stressed individuals. Carbon metabolism, such as fatty acid and amino acid
      catabolism, also tended to shift in unhealthy corals. Genes associated with
      sulfite respiration as well as dimethylsulfoniopropionate degradation have been
      detected, although they have yet to be directly associated with coral disease. In
      addition, genes associated with xenobiotic degradation, antibiotic resistance,
      virulence, and oxidative stress may all be involved in maintaining coral health.
      However, the links between these functional genes and their roles in interacting
      with the coral host are not clear. Continuing identification of coral-associated
      microbial functional genes within the coral holobiont should facilitate advances
      in the field of coral health and disease. 

PMID- 24334359
TI  - Nutrition 411. Urinary tract infection: prevention strategy to improve quality
      measures.

PMID- 24334360
TI  - Opening the dialogue on bowel health.

PMID- 24334361
TI  - A descriptive survey study on the effect of age on quality of life following
      stoma surgery.
AB  - The number of operative procedures involving the creation of an intestinal stoma
      is likely to increase as the population ages. Understanding the role of age on
      postoperative outcomes such as quality of life (QoL) and self-efficacy is
      critical to developing appropriate supportive strategies. A descriptive survey
      study was conducted among 18 patients (11 men seven women, age range 47 to 90
      years) who had an intestinal ostomy created during a 3-year period at the
      University of Alberta Hospital in Edmonton, Alberta, Canada. The Stoma Quality of
      Life Survey and a self-efficacy survey examining self-care, activities of daily
      living, and instrumental activities of daily living were administered. Patient
      records were obtained through a retrospective chart review; of the 57 patients
      identified, 18 were still alive, had not undergone stoma reversal, were
      cognitively competent, and agreed to participate. Seven patients were <65 years
      old and 11 were >=65 years old. Of those, four patients had their stoma since
      2009, four patients since 2010, and 10 patients since 2011. Although older
      patients had more comorbidities and higher mortality following the surgery (46.1%
      for patients >65 versus 26.1%, for patients <65 years old), no statistically
      significant difference was found between the two groups for stoma-associated QoL
      and self-efficacy scores. In patients who had stoma surgery in 2011, older
      patients on average had higher QoL scores (65.21 versus 61.87, maximum score 100,
      P = 0.56), but lower self-efficacy scores (32.50 versus 35.25, maximum score 40,
      P = 0.50). These findings are similar to previously reported study results.
      However, the small study sample size limits analysis of the variables that may
      affect QoL in stoma patients. This study supports the need for additional
      prospective studies to help clinicians develop effective support strategies. 

PMID- 24334362
TI  - Managing severe dermatitis caused by ileal peristomal leakage using a mushroom
      type (de Pezzer) catheter in infants: a case series.
AB  - Skin damage secondary to peristomal leakage is a fairly common complication of
      ileostomies in infants. Traditional conservative measures, including skin
      barriers, ointments, and agents to reduce bowel movements, initially may be
      helpful but not in all patients. The purpose of this case series was to describe
      a new and relatively simple procedure to temporarily manage severe peristomal
      dermatitis caused by ileal peristomal leakage in infants. After obtaining
      informed consent from the parents, a mushroom-type (de Pezzer) catheter was
      inserted into the ileostomy of 11 1- to 4-month-old infants (seven males, four
      females) with severe peristomal dermatitis. Eight had total aganglionic colon
      (TAC), two had meconium ileus (cystic fibrosis), and one had meconium peritonitis
      due to bowel perforation proximal to ileal atresia. The severity of the
      peristomal dermatitis improved remarkably in all patients after 2 to 3 days. In
      eight patients, minimal (if any) dermatitis was noted within 5 to 7 days after
      tube insertion. Six patients who initially had poor weight gain (mean 345
      g/month) developed acceptable weight gain (mean 648 g/month) (P <0.03) within 2
      to 4 months. In seven patients with TAC, the tube was maintained for 2 to 4
      months until definitive pull-through procedure; in four other patients, the tube
      remained in place for 3 to 7 days as a step for preoperative build-up. None of
      the patients developed any complications. The procedure requires the presence of
      a pediatric or trained surgeon, and care must be taken to prevent iatrogenic
      damage. In this case series, an appropriate-size, mushroom-type (de Pezzer)
      catheter placed within the ileostomy was a practical mode for temporary control
      of ileal peristomal leakage that causes severe peristomal dermatitis in infants,
      particularly in those not responding to medical therapy. Larger studies are
      needed to develop evidence-based protocols of care for the prevention and
      management of ileostoma complications in infants. 

PMID- 24334363
TI  - A descriptive study of commonly used postoperative approaches to pediatric stoma
      care in a developing country.
AB  - Construction of an enterostomy is a common procedure in pediatric surgery.
      However, caring for the child with a stoma is challenging for parents in
      developing countries. Modern devices such as colostomy bags and accessories are
      expensive and not readily available. The purpose of this study was to describe
      methods of effluent collection and peristomal skin protection used by the mothers
      of colostomy patients. A prospective, descriptive study was conducted between
      January and December 2011 during the first three postoperative outpatient clinic
      visits among mothers of children who had a colostomy constructed in the authors'
      hospital. The mothers of 44 children (27 males, 17 females, median age 3.3
      months, range 2 days to 11 years) consented to participate. Demographic and
      clinical data were obtained from the records, and mothers were interviewed and
      asked to describe their preferred methods of colostomy effluent collection and
      peristomal skin protection. The stomas also were inspected at each clinic visit.
      Anorectal malformations were the most common indication for a colostomy (32,
      72.73%), followed by Hirschsprung's disease (11, 25%). Forty-two (42) patients
      had a divided sigmoid colostomy (95.45%); two patients had a right loop
      transverse colostomy (4.55%). Nine mothers alternated between two different
      collection methods. The diaper collection method was described most frequently
      (22 out of 53; 41.51%), followed by wraparound waistbands (19; 35.85%) and
      improvised colostomy bags (12; 22.64%). Peristomal skin excoriations were
      commonly seen within the first 3 weeks postsurgery and had mostly disappeared by
      the week 6 postoperative visit. Petrolatum jelly was the most commonly used
      barrier ointment. These locally available, acceptable, and affordable collection
      methods may be useful for children in other developing countries. 

PMID- 24334364
TI  - A retrospective analysis of a human cellular repair matrix for the treatment of
      chronic wounds.
AB  - Despite the introduction of advanced wound care modalities over the last 15
      years, chronic wounds are an increasing problem. Few single options are available
      for clinicians to treat recalcitrant wounds such as diabetic foot ulcers (DFUs)
      and venous leg ulcers (VLUs). A retrospective, single-center study was conducted
      at an outpatient wound care center to evaluate the clinical effect of a human
      cellular repair matrix (h-CRM) on chronic wounds that had failed to heal. Data
      from all patients who had received this treatment modality during a period of 2
      years were abstracted. Standard care included weekly visits, regular debridement,
      offloading DFUs, compression for VLUs, and h-CRM for wounds >4 weeks duration. A
      total of 66 patients (30 male, 36 female, mean age 71.1 [+/- 8.8] years) received
      h-CRM treatment for 67 wounds (34 VLUs, 27 DFUs, and six other chronic wounds).
      The average wound size at baseline was 6.65 (+/- 9.68) cm2, and the average wound
      duration before h-CRM treatment was 38 (+/-70.8) weeks. Fifty (50) patients
      (74.6%) had failed to heal using other advanced therapies. After 12 weeks of
      care, 51 of the 67 wounds (76.1%) were healed: 23 of 34 (67.6%) VLUs and 23 of 27
      (85.2%) DFUs. Average time to closure in these wounds was 5.8 (+/-2.5) weeks. No
      significant differences were found between proportions of VLUs and DFUs healed.
      No adverse events or recurrences occurred during an average follow-up time of
      20.4 months (range 11 to 32 months). Overall, patients received an average of 3.8
      applications of h-CRM, and 3.2 applications were used among patients that healed.
      The study results suggest h-CRM may benefit patients with chronic wounds.
      Prospective, randomized clinical studies are warranted. 

PMID- 24334365
TI  - Comparison of the magnetic, radiolabeling, hyperthermic and biodistribution
      properties of hybrid nanoparticles bearing CoFe2O4 and Fe3O4 metal cores.
AB  - Metal oxide nanoparticles, hybridized with various polymeric chemicals, represent
      a novel and breakthrough application in drug delivery, hyperthermia treatment and
      imaging techniques. Radiolabeling of these nanoformulations can result in new and
      attractive dual-imaging agents as well as provide accurate in vivo information on
      their biodistribution profile. In this paper a comparison study has been made
      between two of the most promising hybrid core-shell nanosystems, bearing either
      magnetite (Fe3O4) or cobalt ferrite (CoFe2O4) cores, regarding their magnetic,
      radiolabeling, hyperthermic and biodistribution properties. While hyperthermic
      properties were found to be affected by the metal-core type, the radiolabeling
      ability and the in vivo fate of the nanoformulations seem to depend critically on
      the size and the shell composition. 

PMID- 24334366
TI  - In vivo kinematics of the talocrural and subtalar joints during weightbearing
      ankle rotation in chronic ankle instability.
AB  - BACKGROUND: Chronic ankle instability (CAI) results in abnormal ankle kinematics,
      but there exists limited quantitative data characterizing these alterations. This
      study was undertaken to investigate kinematic alterations of the talocrural and
      subtalar joints in CAI. METHODS: A total of 14 male patients with unilateral CAI
      (mean age = 21.1 +/- 2.5 years) were enrolled. Computed tomography and
      fluoroscopic imaging of both lower extremities during weightbearing passive ankle
      joint complex (AJC) rotation were obtained. Three-dimensional bone models created
      from the computed tomography images were matched with the fluoroscopic images to
      compute the 6 degrees-of-freedom talocrural, subtalar, and AJC kinematics.
      RESULTS: In 20 degrees  plantarflexion, ankles with CAI demonstrated
      significantly increased anterior translation of the talocrural joint during AJC
      internal rotation from 5 degrees  to 7 degrees  and significantly decreased
      talocrural internal rotation within an AJC arc of motion from -1 degrees  to 5
      degrees . CAI joints demonstrated significantly increased internal rotation of
      the subtalar joint within an AJC arc of motion from -1 degrees  to 3 degrees .
      DISCUSSION: In CAI, altered subtalar internal rotation occurs with increased
      talocrural anterior translation and reduced talocrural internal rotation during
      weightbearing ankle internal rotation in plantarflexion. These results suggest
      that altered subtalar mechanics may contribute to CAI symptoms.

PMID- 24334367
TI  - The use of dual C-arms during fixation of calcaneal fractures: a technique tip.
AB  - We describe a simple technique using dual C-arms (large and mini C-arm together)
      for open reduction internal fixation of calcaneal fractures in the lateral
      decubitus position that (1) decreases the difficulty of obtaining proper
      intraoperative imaging; (2) limits C-arm movement, which decreases risk of
      contamination and operative time; and (3) minimizes the drawbacks of each imaging
      fluoroscopic modality. LEVELS OF EVIDENCE: Level V, Technical tip, Expert
      opinion.

PMID- 24334368
TI  - Outcomes and safety of endoscopic tarsal tunnel decompression: a systematic
      review.
AB  - Open surgical decompression of the tarsal tunnel is the standard surgical
      approach for compression of the tibial nerve within the tarsal tunnel.
      Complications associated with this approach can be significant and periods of non
      weight bearing are required. An alternative approach allowing for minimal soft
      tissue trauma and reduced time to ambulation is therefore desirable. Endoscopic
      tarsal tunnel decompression may provide such an alternative. The authors
      performed a systematic review of electronic databases and other relevant sources
      to identify material regarding the safety of endoscopic tarsal tunnel
      decompression. Only articles that included clear information concerning the
      safety of endoscopic tarsal tunnel decompression with a follow-up of at least 12
      months were included. Three studies were identified involving 37 feet, with a
      weighted mean follow-up of 27 months. There were no permanent complications
      relating to iatrogenic nerve injury, deep infection, or prolonged wound healing
      problems documented despite initiating ambulation within one week of surgery. Two
      patients (5.6%) developed recurrence more than 2 years postoperative and one
      (2.7%) showed no improvement. Endoscopic tarsal tunnel decompression is a safe
      procedure with a low rate of recurrence or failure and allows for near-immediate
      ambulation. However, additional prospective investigations comparing open and
      endoscopic approaches to tarsal tunnel decompression are warranted.

PMID- 24334369
TI  - Repair of acute extensor hallucis longus tendon injuries: a retrospective review.
AB  - BACKGROUND: Extensor hallucis longus (EHL) tendon injuries may occur with
      lacerations sustained over the dorsum of the foot and lead to hallux dysfunction.
      Primary repair is performed when tendon edges are opposable; however, if a gap
      exists between tendon edges, then reconstruction with tendon graft or tendon
      transfer may be necessary to restore hallux alignment and dorsiflexion. We
      describe the surgical technique and report the results on a large series of
      patients having undergone primary repair or reconstruction of EHL tendon
      lacerations. METHODS: We retrospectively reviewed all patients undergoing EHL
      tendon repair or reconstruction between January 2005 and May 2012. Information on
      patient demographics, mechanism of injury, time to surgery, intraoperative
      findings, surgical repair or reconstruction technique, and postoperative function
      were collected. Patients were contacted by telephone for administration of the
      Foot and Ankle Ability Measure (FAAM) and American Orthopaedic Foot and Ankle
      Society Hallux questionnaires. RESULTS: Twenty of 23 patients undergoing EHL
      tendon repair or reconstruction were available for review at an average clinical
      follow-up of 12 months (range 3-89 months) and an average telephone follow-up of
      5.1 years (range 1-10.4 years). Primary EHL repair was performed in 80% of cases,
      with the remaining patients undergoing reconstruction with deep tendon transfer
      of the extensor digitorum longus tendon from the second toe. At final follow-up,
      19 of 20 patients had active hallux dorsiflexion. The average FAAM Activities of
      Daily Living score was 94.2% (range 58.3% to 100%) and the average FAAM Sports
      score was 94.2% (range 65.6% to 100%). CONCLUSION: Primary repair or
      reconstruction of EHL tendon lacerations is a reliable procedure that restores
      hallux alignment and function in most patients as measured by the validated FAAM
      questionnaire. Deep tendon transfer from the extensor digitorum longus may be
      performed if EHL tendon edges are not opposable thus eliminating the need for
      allograft reconstruction.

PMID- 24334370
TI  - Health assets for adolescents: opinions from a neighbourhood in Spain.
AB  - This study uses a health asset (HA) framework to explore current perspectives on
      health, wellbeing and their determinants amongst a group of 15-18-year-old
      adolescents living in the neighbourhood of Zaidin (Granada, Spain). The study was
      carried out in Summer 2011 using a qualitative approach. It included 20 semi
      structured interviews, 2 focus groups with adolescents and 4 semi-structured
      interviews with key informants (adults who work with adolescents). Narrative data
      were analysed by means of content analysis methodology, considering the concept
      of health, HAs and how they are prioritized as dimensions for the analysis. The
      concept of health defined by adolescents involves physical, psychological and
      social dimensions. According to them, health is associated with happiness and
      quality of life. A range of HAs were identified and classified as internal
      (belonging to the adolescents) and external or contextual. Internal assets are
      classified into three types: personal traits (assets of 'being'), behaviour
      (assets of 'doing') and social resources which contribute to their feeling of
      health and well-being (assets of 'having'). The latter connects internal and
      external assets. The classification of HAs ('being', 'doing' and 'having')
      proposed in this study provides a useful starting framework of thinking about how
      these assets could be organized to support the development of health promotion
      programmes. The study highlights the opportunity for public policy to contribute
      to the improvement of the conditions and local scenarios that improve the
      possibilities for positive connections at the community level. 

PMID- 24334371
TI  - Three dimensional visualization of engineered bone and soft tissue by combined x
      ray micro-diffraction and phase contrast tomography.
AB  - Computed x-ray phase contrast micro-tomography is the most valuable tool for a
      three dimensional (3D) and non destructive analysis of the tissue engineered bone
      morphology. We used a Talbot interferometer installed at SYRMEP beamline of the
      ELETTRA synchrotron (Trieste, Italy) for a precise 3D reconstruction of both bone
      and soft connective tissue, regenerated in vivo within a porous scaffold. For the
      first time the x-ray tomographic reconstructions have been combined with x-ray
      scanning micro-diffraction measurement on the same sample, in order to give an
      exhaustive identification of the different tissues participating to the
      biomineralization process. As a result, we were able to investigate in detail the
      different densities in the tissues, distinguishing the 3D organization of the
      amorphous calcium phosphate from the collagen matrix. Our experimental approach
      allows for a deeper understanding of the role of collagen matrix in the organic
      mineral transition, which is a crucial issue for the development of new bio
      inspired composites. 

PMID- 24334372
TI  - [Performance of users in tropical areas with the BI-RADS classification of breast
      lesions for predicting malignancy].
AB  - OBJECTIVES: To evaluate the diagnostic performance of radiologists in Cameroon
      using the BI-RADS classification to interpret mammograms and ultrasound scans
      together for the prediction of malignant breast lesions. METHODS: This cross
      sectional study took place at the Women's and Children's Hospital in Yaounde from
      July 2009 to April 2010 and included 211 women with breast lesions identified on
      mammograms during a breast screening campaign and subsequently assessed with
      ultrasonography and histology. The BI-RADS classifications of these lesions were
      compared to the corresponding histology results to evaluate the accuracy of
      predictions of malignancy from the mammograms and ultrasound scans interpreted
      with the BI-RADS system. The rate of malignancy in each ACR-classified category
      was also compared to the standard ACR categories as stipulated in the ACR
      classification. RESULTS: In all, 339 women aged from 16 to 78 years were
      screened, and lesions requiring biopsies were identified for 211. The age group
      included most often was the 41-50 year-old group (n = 98, 46.4%). Overall, 135
      (64%) women had benign lesions and 76 (36%) malignant. Invasive carcinoma was
      found in 49 (65%) of the malignant lesions, in situ intraductal carcinoma in 23
      (30%), and sarcoma in 4 (5%). Based on the BI-RADS classification, 124 (58.7%)
      breast lesions were classified as ACR2, 15 (7.1%) as ACR3, 44 (20.8%) as ACR4,
      and 28 (13.3%) as ACR5. Comparison of the BI-RADS classification and the
      histological findings showed that 19% of ACR2-classified lesions were malignant,
      13% of those classified ACR3, 66% ACR4, and 75% ACR5. The global accuracy in the
      prediction of malignancy the BI-RADS classification was 77.3%. CONCLUSION: The
      accuracy of the radiologists using the BI-RADS classification in our hospital was
      good at 77.3%, although shortcomings in the evaluation and interpretation of some
      lesions resulted in a relatively high prevalence of malignant lesions in
      categories ACR2 and ACR3.

PMID- 24334373
TI  - Photo-patternable ion gel-gated graphene transistors and inverters on plastic.
AB  - We demonstrate photo-patternable ion gel-gated graphene transistors and inverters
      on plastic substrates. The photo-patternable ion gel can be used as a negative
      photoresist for the patterning of underlying graphene as well as gate
      dielectrics. As a result, an extra graphene-patterning step is not required,
      which simplifies the device fabrication and avoids a side effect arising from the
      photoresist residue. The high capacitance of ion gel gate dielectrics yielded a
      low voltage operation (~2 V) of the graphene transistor and inverter. The
      graphene transistors on plastic showed an on/off-current ratio of ~11.5, along
      with hole and electron mobilities of 852 +/- 124 and 452 +/- 98 cm(2) V(-1) s(
      1), respectively. In addition, the flexible graphene inverter was successfully
      fabricated on plastic through the potential superposition effect from the drain
      bias. These devices show excellent mechanical flexibility and fatigue stability.

PMID- 24334374
TI  - Nanoscale electrical and structural modification induced by rapid thermal
      oxidation of AlGaN/GaN heterostructures.
AB  - In this paper, the structural and electrical modifications induced, in the
      nanoscale, by a rapid thermal oxidation process on AlGaN/GaN heterostructures,
      are investigated. A local rapid oxidation (900  degrees  C in O2, 10 min)
      localized under the anode region of an AlGaN/GaN diode enabled a reduction of the
      leakage current with respect to a standard Schottky contact. The insulating
      properties of the near-surface oxidized layer were probed by a nanoscale
      electrical characterization using scanning probe microscopy techniques. The
      structural characterization indicated the formation of a thin uniform oxide layer
      on the surface, with preferential oxidation paths along V-shaped defects
      penetrating through the AlGaN/GaN interface. The oxidation process resulted in an
      expansion of the lattice parameters due to the incorporation of oxygen atoms,
      accompanied by an increase of the crystal mosaicity. As a consequence, a decrease
      of the sheet carrier density of the two-dimensional electron gas and a positive
      shift of the threshold voltage are observed. The results provide useful insights
      for a possible future integration of rapid oxidation processes during GaN device
      fabrication.

PMID- 24334375
TI  - The phototropic response is locally regulated within the topmost light-responsive
      region of the Arabidopsis thaliana seedling.
AB  - Phototropism is caused by differential cell elongation between the irradiated and
      shaded sides of plant organs, such as the stem. It is widely accepted that an
      uneven auxin distribution between the two sides crucially participates in this
      response. Plant-specific blue-light photoreceptors, phototropins (phot1 and
      phot2), mediate this response. In grass coleoptiles, the sites of light
      perception and phototropic bending are spatially separated. However, these sites
      are less clearly distinguished in dicots. Furthermore, the exact placement of the
      action of each phototropic signaling factor remains unknown. Here, we
      investigated the spatial aspects of phototropism using spotlight irradiation with
      etiolated Arabidopsis seedlings. The results demonstrated that the topmost part
      of about 1.1 mm of the hypocotyl constituted the light-responsive region in which
      both light perception and actual bending occurred. In addition, cotyledons and
      the shoot apex were dispensable for the response. Hence, the response was more
      region autonomous in dicots than in monocots. We next examined the elongation
      rates, the levels of phot1 and the auxin-reporter gene expression along the
      hypocotyl during the phototropic response. The light-responsive region was more
      active than the non-responsive region with respect to all of those parameters. 

PMID- 24334376
TI  - Characterization of volatile compounds responsible for the aroma in naturally
      fermented sausages by gas chromatography-olfactometry.
AB  - The objective of this study was to characterize naturally fermented dry sausages
      produced without the use of microbial starters and to determine which odour
      active compounds are responsible for their aroma. The traditional manufacture was
      responsible for different chemical characteristics and consumer's acceptance. The
      volatile compounds detected in the headspace comprised a complex mixture of
      volatile compounds derived from bacterial metabolism (mainly esterase activity of
      Staphyloccoci), spices and lipid auto-oxidation. The odour-active volatile
      compounds were identified using gas chromatography coupled to olfactometry (GC-O)
      using the detection frequency method. The aroma profile was characterized by the
      presence of several compounds such as acetic acid, ethyl butanoate, hexanal,
      methional, 1-octen-3-ol, benzeneacetaldehyde and 4-methyl-phenol. However,
      naturally fermented sausages were also characterized by numerous esters, both
      ethyl and methyl esters, which impart a wide variety of fruity notes. 

PMID- 24334378
TI  - Extending the algebraic formalism for genome rearrangements to include linear
      chromosomes.
AB  - Algebraic rearrangement theory, as introduced by Meidanis and Dias, focuses on
      representing the order in which genes appear in chromosomes, and applies to
      circular chromosomes only. By shifting our attention to genome adjacencies, we
      introduce the adjacency algebraic theory, extending the original algebraic theory
      to linear chromosomes in a very natural way, also allowing the original algebraic
      distance formula to be used to the general multichromosomal case, with both
      linear and circular chromosomes. The resulting distance, which we call algebraic
      distance here, is very similar to, but not quite the same as, double-cut-and-join
      distance. We present linear time algorithms to compute it and to sort genomes. We
      show how to compute the rearrangement distance from the adjacency graph, for an
      easier comparison with other rearrangement distances. A thorough discussion on
      the relationship between the chromosomal and adjacency representation is also
      given, and we show how all classic rearrangement operations can be modeled using
      the algebraic theory. 

PMID- 24334377
TI  - The Dutch hospital standardised mortality ratio (HSMR) method and cardiac
      surgery: benchmarking in a national cohort using hospital administration data
      versus a clinical database.
AB  - OBJECTIVE: To compare the accuracy of data from hospital administration databases
      and a national clinical cardiac surgery database and to compare the performance
      of the Dutch hospital standardised mortality ratio (HSMR) method and the logistic
      European System for Cardiac Operative Risk Evaluation, for the purpose of
      benchmarking of mortality across hospitals. METHODS: Information on all patients
      undergoing cardiac surgery between 1 January 2007 and 31 December 2010 in 10
      centres was extracted from The Netherlands Association for Cardio-Thoracic
      Surgery database and the Hospital Discharge Registry. The number of cardiac
      surgery interventions was compared between both databases. The European System
      for Cardiac Operative Risk Evaluation and hospital standardised mortality ratio
      models were updated in the study population and compared using the C-statistic,
      calibration plots and the Brier-score. RESULTS: The number of cardiac surgery
      interventions performed could not be assessed using the administrative database
      as the intervention code was incorrect in 1.4-26.3%, depending on the type of
      intervention. In 7.3% no intervention code was registered. The updated
      administrative model was inferior to the updated clinical model with respect to
      discrimination (c-statistic of 0.77 vs 0.85, p<0.001) and calibration (Brier
      Score of 2.8% vs 2.6%, p<0.001, maximum score 3.0%). Two average performing
      hospitals according to the clinical model became outliers when benchmarking was
      performed using the administrative model. CONCLUSIONS: In cardiac surgery,
      administrative data are less suitable than clinical data for the purpose of
      benchmarking. The use of either administrative or clinical risk-adjustment models
      can affect the outlier status of hospitals. Risk-adjustment models including
      procedure-specific clinical risk factors are recommended.

PMID- 24334379
TI  - 2D meets 4G: G-quadruplexes in RNA secondary structure prediction.
AB  - G-quadruplexes are abundant locally stable structural elements in nucleic acids.
      The combinatorial theory of RNA structures and the dynamic programming algorithms
      for RNA secondary structure prediction are extended here to incorporate G
      quadruplexes using a simple but plausible energy model. With preliminary energy
      parameters, we find that the overwhelming majority of putative quadruplex-forming
      sequences in the human genome are likely to fold into canonical secondary
      structures instead. Stable G-quadruplexes are strongly enriched, however, in the
      5'UTR of protein coding mRNAs.

PMID- 24334380
TI  - Proximity measures for clustering gene expression microarray data: a validation
      methodology and a comparative analysis.
AB  - Cluster analysis is usually the first step adopted to unveil information from
      gene expression microarray data. Besides selecting a clustering algorithm,
      choosing an appropriate proximity measure (similarity or distance) is of great
      importance to achieve satisfactory clustering results. Nevertheless, up to date,
      there are no comprehensive guidelines concerning how to choose proximity measures
      for clustering microarray data. Pearson is the most used proximity measure,
      whereas characteristics of other ones remain unexplored. In this paper, we
      investigate the choice of proximity measures for the clustering of microarray
      data by evaluating the performance of 16 proximity measures in 52 data sets from
      time course and cancer experiments. Our results support that measures rarely
      employed in the gene expression literature can provide better results than
      commonly employed ones, such as Pearson, Spearman, and euclidean distance. Given
      that different measures stood out for time course and cancer data evaluations,
      their choice should be specific to each scenario. To evaluate measures on time
      course data, we preprocessed and compiled 17 data sets from the microarray
      literature in a benchmark along with a new methodology, called Intrinsic
      Biological Separation Ability (IBSA). Both can be employed in future research to
      assess the effectiveness of new measures for gene time-course data. 

PMID- 24334381
TI  - A closed-loop control scheme for steering steady states of glycolysis and
      glycogenolysis pathway.
AB  - Biochemical networks normally operate in the neighborhood of one of its multiple
      steady states. It may reach from one steady state to other within a finite time
      span. In this paper, a closed-loop control scheme is proposed to steer states of
      the glycolysis and glycogenolysis (GG) pathway from one of its steady states to
      other. The GG pathway is modeled in the synergism and saturation system
      formalism, known as S-system. This S-system model is linearized into the
      controllable Brunovsky canonical form using a feedback linearization technique.
      For closed-loop control, the linear-quadratic regulator (LQR) and the linear
      quadratic gaussian (LQG) regulator are invoked to design a controller for
      tracking prespecified steady states. In the feedback linearization technique, a
      global diffeomorphism function is proposed that facilitates in achieving the
      regulation requirement. The robustness of the regulated GG pathway is studied
      considering input perturbation and with measurement noise. 

PMID- 24334382
TI  - A divide and conquer approach for construction of large-scale signaling networks
      from PPI and RNAi data using linear programming.
AB  - Inference of topology of signaling networks from perturbation experiments is a
      challenging problem. Recently, the inference problem has been formulated as a
      reference network editing problem and it has been shown that finding the minimum
      number of edit operations on a reference network to comply with perturbation
      experiments is an NP-complete problem. In this paper, we propose an integer
      linear optimization (ILP) model for reconstruction of signaling networks from
      RNAi data and a reference network. The ILP model guarantees the optimal solution;
      however, is practical only for small signaling networks of size 10-15 genes due
      to computational complexity. To scale for large signaling networks, we propose a
      divide and conquer-based heuristic, in which a given reference network is divided
      into smaller subnetworks that are solved separately and the solutions are merged
      together to form the solution for the large network. We validate our proposed
      approach on real and synthetic data sets, and comparison with the state of the
      art shows that our proposed approach is able to scale better for large networks
      while attaining similar or better biological accuracy. 

PMID- 24334383
TI  - A knowledge-based multiple-sequence alignment algorithm.
AB  - A common and cost-effective mechanism to identify the functionalities,
      structures, or relationships between species is multiple-sequence alignment, in
      which DNA/RNA/protein sequences are arranged and aligned so that similarities
      between sequences are clustered together. Correctly identifying and aligning
      these sequence biological similarities help from unwinding the mystery of species
      evolution to drug design. We present our knowledge-based multiple sequence
      alignment (KB-MSA) technique that utilizes the existing knowledge databases such
      as SWISSPROT, GENBANK, or HOMSTRAD to provide a more realistic and reliable
      sequence alignment. We also provide a modified version of this algorithm (CB-MSA)
      that utilizes the sequence consistency information when sequence knowledge
      databases are not available. Our benchmark tests on BAliBASE, PREFAB, HOMSTRAD,
      and SABMARK references show accuracy improvements up to 10 percent on twilight
      data sets against many leading alignment tools such as ISPALIGN, PADT, CLUSTALW,
      MAFFT, PROBCONS, and T-COFFEE. 

PMID- 24334384
TI  - A two-phase bio-NER system based on integrated classifiers and multiagent
      strategy.
AB  - Biomedical named entity recognition (Bio-NER) is a fundamental step in biomedical
      text mining. This paper presents a two-phase Bio-NER model targeting at JNLPBA
      task. Our two-phase method divides the task into two subtasks: named entity
      detection (NED) and named entity classification (NEC). The NED subtask is
      accomplished based on the two-layer stacking method in the first phase, where
      named entities (NEs) are distinguished from nonnamed-entities (NNEs) in
      biomedical literatures without identifying their types. Then six classifiers are
      constructed by four toolkits (CRF++, YamCha, maximum entropy, Mallet) with
      different training methods and integrated based on the two-layer stacking method.
      In the second phase for the NEC subtask, the multiagent strategy is introduced to
      determine the correct entity type for entities identified in the first phase. The
      experiment results show that the presented approach can achieve an F-score of
      76.06 percent, which outperforms most of the state-of-the-art systems. 

PMID- 24334385
TI  - An improved approximation algorithm for scaffold filling to maximize the common
      adjacencies.
AB  - Scaffold filling is a new combinatorial optimization problem in genome
      sequencing. The one-sided scaffold filling problem can be described as given an
      incomplete genome I and a complete (reference) genome G, fill the missing genes
      into I such that the number of common (string) adjacencies between the resulting
      genome I' and G is maximized. This problem is NP-complete for genome with
      duplicated genes and the best known approximation factor is 1.33, which uses a
      greedy strategy. In this paper, we prove a better lower bound of the optimal
      solution, and devise a new algorithm by exploiting the maximum matching method
      and a local improvement technique, which improves the approximation factor to
      1.25. For genome with gene repetitions, this is the only known NP-complete
      problem which admits an approximation with a small constant factor (less than
      1.5).

PMID- 24334386
TI  - An optimization rule for in silico identification of targeted overproduction in
      metabolic pathways.
AB  - In an extension of previous work, here we introduce a second-order optimization
      method for determining optimal paths from the substrate to a target product of a
      metabolic network, through which the amount of the target is maximum. An
      objective function for the said purpose, along with certain linear constraints,
      is considered and minimized. The basis vectors spanning the null space of the
      stoichiometric matrix, depicting the metabolic network, are computed, and their
      convex combinations satisfying the constraints are considered as flux vectors. A
      set of other constraints, incorporating weighting coefficients corresponding to
      the enzymes in the pathway, are considered. These weighting coefficients appear
      in the objective function to be minimized. During minimization, the values of
      these weighting coefficients are estimated and learned. These values, on
      minimization, represent an optimal pathway, depicting optimal enzyme
      concentrations, leading to overproduction of the target. The results on various
      networks demonstrate the usefulness of the methodology in the domain of metabolic
      engineering. A comparison with the standard gradient descent and the extreme
      pathway analysis technique is also performed. Unlike the gradient descent method,
      the present method, being independent of the learning parameter, exhibits
      improved results. 

PMID- 24334387
TI  - Algebraic representation of asynchronous multiple-valued networks and its
      dynamics.
AB  - In this paper, dynamics of asynchronous multiple-valued networks (AMVNs) are
      investigated based on linear representation. By semitensor product of matrices,
      we convert AMVNs into the discrete-time linear representation. A general formula
      to calculate all of network transition matrices of a specific AMVN is achieved. A
      necessary and sufficient algebraic criterion to determine whether a given state
      belongs to loose attractors of length s is proposed. Formulas for the numbers of
      attractors in AMVNs are provided. Finally, algorithms are presented to detect all
      of the attractors and basins. Examples are shown to demonstrate the feasibility
      of the proposed scheme.

PMID- 24334388
TI  - Algorithms for genome-scale phylogenetics using gene tree parsimony.
AB  - The use of genomic data sets for phylogenetics is complicated by the fact that
      evolutionary processes such as gene duplication and loss, or incomplete lineage
      sorting (deep coalescence) cause incongruence among gene trees. One well-known
      approach that deals with this complication is gene tree parsimony, which, given a
      collection of gene trees, seeks a species tree that requires the smallest number
      of evolutionary events to explain the incongruence of the gene trees. However, a
      lack of efficient algorithms has limited the use of this approach. Here, we
      present efficient algorithms for SPR and TBR-based local search heuristics for
      gene tree parsimony under the 1) duplication, 2) loss, 3) duplication-loss, and
      4) deep coalescence reconciliation costs. These novel algorithms improve upon the
      time complexities of previous algorithms for these problems by a factor of n,
      where n is the number of species in the collection of gene trees. Our algorithms
      provide a substantial improvement in runtime and scalability compared to previous
      implementations and enable large-scale gene tree parsimony analyses using any of
      the four reconciliation costs. Our algorithms have been implemented in the
      software packages DupTree and iGTP, and have already been used to perform several
      compelling phylogenetic studies.

PMID- 24334389
TI  - Analytical solution of steady-state equations for chemical reaction networks with
      bilinear rate laws.
AB  - True steady states are a rare occurrence in living organisms, yet their knowledge
      is essential for quasi-steady-state approximations, multistability analysis, and
      other important tools in the investigation of chemical reaction networks (CRN)
      used to describe molecular processes on the cellular level. Here, we present an
      approach that can provide closed form steady-state solutions to complex systems,
      resulting from CRN with binary reactions and mass-action rate laws. We map the
      nonlinear algebraic problem of finding steady states onto a linear problem in a
      higher-dimensional space. We show that the linearized version of the steady-state
      equations obeys the linear conservation laws of the original CRN. We identify two
      classes of problems for which complete, minimally parameterized solutions may be
      obtained using only the machinery of linear systems and a judicious choice of the
      variables used as free parameters. We exemplify our method, providing explicit
      formulae, on CRN describing signal initiation of two important types of RTK
      receptor-ligand systems, VEGF and EGF-ErbB1. 

PMID- 24334390
TI  - Characterizing the topology of probabilistic biological networks.
AB  - Biological interactions are often uncertain events, that may or may not take
      place with some probability. This uncertainty leads to a massive number of
      alternative interaction topologies for each such network. The existing studies
      analyze the degree distribution of biological networks by assuming that all the
      given interactions take place under all circumstances. This strong and often
      incorrect assumption can lead to misleading results. In this paper, we address
      this problem and develop a sound mathematical basis to characterize networks in
      the presence of uncertain interactions. Using our mathematical representation, we
      develop a method that can accurately describe the degree distribution of such
      networks. We also take one more step and extend our method to accurately compute
      the joint-degree distributions of node pairs connected by edges. The number of
      possible network topologies grows exponentially with the number of uncertain
      interactions. However, the mathematical model we develop allows us to compute
      these degree distributions in polynomial time in the number of interactions. Our
      method works quickly even for entire protein-protein interaction (PPI) networks.
      It also helps us find an adequate mathematical model using MLE. We perform a
      comparative study of node-degree and joint-degree distributions in two types of
      biological networks: the classical deterministic networks and the more flexible
      probabilistic networks. Our results confirm that power-law and log-normal models
      best describe degree distributions for both probabilistic and deterministic
      networks. Moreover, the inverse correlation of degrees of neighboring nodes shows
      that, in probabilistic networks, nodes with large number of interactions prefer
      to interact with those with small number of interactions more frequently than
      expected. We also show that probabilistic networks are more robust for node
      degree distribution computation than the deterministic ones. AVAILABILITY: all
      the data sets used, the software implemented and the alignments found in this
      paper are available at http://bioinformatics.cise.ufl.edu/projects/probNet/.

PMID- 24334391
TI  - Decomposition of flux distributions into metabolic pathways.
AB  - Genome-scale reconstructions are often used for studying relationships between
      fundamental components of a metabolic system. In this study, we develop a novel
      computational method for analyzing predicted flux distributions for metabolic
      reconstructions. Because chemical reactions may have multiple reactants and
      products, a directed hypergraph where hyperarcs may have multiple tail vertices
      and head vertices is a more appropriate representation of the metabolic network
      than a conventional network. We use this view to represent predicted flux
      distributions by maximum generalized flows on hypergraphs. We then demonstrate
      that the generalized hyperflow problem may be transformed to an equivalent
      network flow problem with side constraints. This transformation allows a flux to
      be decomposed into chains of reactions. Subsequent analysis of these chains helps
      to characterize active pathways in a flux distribution. Such characterizations
      facilitate comparisons of flux distributions for different environmental
      conditions. The proposed method is applied to compare predicted flux
      distributions for Salmonella typhimurium to study changes in metabolism that
      cause enhanced virulence during a space flight. The differences between flux
      distributions corresponding to normal and enhanced virulence states confirm
      previous observations concerning infection mechanisms and suggest new pathways
      for exploration. 

PMID- 24334392
TI  - Designing template-free predictor for targeting protein-ligand binding sites with
      classifier ensemble and spatial clustering.
AB  - Accurately identifying the protein-ligand binding sites or pockets is of
      significant importance for both protein function analysis and drug design.
      Although much progress has been made, challenges remain, especially when the 3D
      structures of target proteins are not available or no homology templates can be
      found in the library, where the template-based methods are hard to be applied. In
      this paper, we report a new ligand-specific template-free predictor called
      TargetS for targeting protein-ligand binding sites from primary sequences.
      TargetS first predicts the binding residues along the sequence with ligand
      specific strategy and then further identifies the binding sites from the
      predicted binding residues through a recursive spatial clustering algorithm.
      Protein evolutionary information, predicted protein secondary structure, and
      ligand-specific binding propensities of residues are combined to construct
      discriminative features; an improved AdaBoost classifier ensemble scheme based on
      random undersampling is proposed to deal with the serious imbalance problem
      between positive (binding) and negative (nonbinding) samples. Experimental
      results demonstrate that TargetS achieves high performances and outperforms many
      existing predictors. TargetS web server and data sets are freely available at:
      http://www.csbio.sjtu.edu.cn/bioinf/TargetS/ for academic use. 

PMID- 24334393
TI  - GeneOnEarth: fitting genetic PC plots on the globe.
AB  - Principal component (PC) plots have become widely used to summarize genetic
      variation of individuals in a sample. The similarity between genetic distance in
      PC plots and geographical distance has shown to be quite impressive. However, in
      most situations, individual ancestral origins are not precisely known or they are
      heterogeneously distributed; hence, they are hardly linked to a geographical
      area. We have developed GeneOnEarth, a user-friendly web-based tool to help
      geneticists to understand whether a linear isolation-by-distance model may apply
      to a genetic data set; thus, genetic distances among a set of individuals
      resemble geographical distances among their origins. Its main goal is to allow
      users to first apply a by-view Procrustes method to visually learn whether this
      model holds. To do that, the user can choose the exact geographical area from an
      on line 2D or 3D world map by using, respectively, Google Maps or Google Earth,
      and rotate, flip, and resize the images. GeneOnEarth can also compute the optimal
      rotation angle using Procrustes analysis and assess statistical evidence of
      similarity when a different rotation angle has been chosen by the user. An online
      version of GeneOnEarth is available for testing and using purposes at
      http://bios.ugr.es/GeneOnEarth.

PMID- 24334394
TI  - Identification of DNA-binding and protein-binding proteins using enhanced graph
      wavelet features.
AB  - Interactions between biomolecules play an essential role in various biological
      processes. For predicting DNA-binding or protein-binding proteins, many machine
      learning-based techniques have used various types of features to represent the
      interface of the complexes, but they only deal with the properties of a single
      atom in the interface and do not take into account the information of
      neighborhood atoms directly. This paper proposes a new feature representation
      method for biomolecular interfaces based on the theory of graph wavelet. The
      enhanced graph wavelet features (EGWF) provides an effective way to characterize
      interface feature through adding physicochemical features and exploiting a graph
      wavelet formulation. Particularly, graph wavelet condenses the information around
      the center atom, and thus enhances the discrimination of features of biomolecule
      binding proteins in the feature space. Experiment results show that EGWF performs
      effectively for predicting DNA-binding and protein-binding proteins in terms of
      Matthew's correlation coefficient (MCC) score and the area value under the
      receiver operating characteristic curve (AUC). 

PMID- 24334395
TI  - Pareto optimality in organelle energy metabolism analysis.
AB  - In low and high eukaryotes, energy is collected or transformed in compartments,
      the organelles. The rich variety of size, characteristics, and density of the
      organelles makes it difficult to build a general picture. In this paper, we make
      use of the Pareto-front analysis to investigate the optimization of energy
      metabolism in mitochondria and chloroplasts. Using the Pareto optimality
      principle, we compare models of organelle metabolism on the basis of single- and
      multiobjective optimization, approximation techniques (the Bayesian Automatic
      Relevance Determination), robustness, and pathway sensitivity analysis. Finally,
      we report the first analysis of the metabolic model for the hydrogenosome of
      Trichomonas vaginalis, which is found in several protozoan parasites. Our
      analysis has shown the importance of the Pareto optimality for such comparison
      and for insights into the evolution of the metabolism from cytoplasmic to
      organelle bound, involving a model order reduction. We report that Pareto fronts
      represent an asymptotic analysis useful to describe the metabolism of an organism
      aimed at maximizing concurrently two or more metabolite concentrations. 

PMID- 24334396
TI  - Protein function prediction using multilabel ensemble classification.
AB  - High-throughput experimental techniques produce several kinds of heterogeneous
      proteomic and genomic data sets. To computationally annotate proteins, it is
      necessary and promising to integrate these heterogeneous data sources. Some
      methods transform these data sources into different kernels or feature
      representations. Next, these kernels are linearly (or nonlinearly) combined into
      a composite kernel. The composite kernel is utilized to develop a predictive
      model to infer the function of proteins. A protein can have multiple roles and
      functions (or labels). Therefore, multilabel learning methods are also adapted
      for protein function prediction. We develop a transductive multilabel classifier
      (TMC) to predict multiple functions of proteins using several unlabeled proteins.
      We also propose a method called transductive multilabel ensemble classifier
      (TMEC) for integrating the different data sources using an ensemble approach. The
      TMEC trains a graph-based multilabel classifier on each single data source, and
      then combines the predictions of the individual classifiers. We use a directed
      birelational graph to capture the relationships between pairs of proteins,
      between pairs of functions, and between proteins and functions. We evaluate the
      effectiveness of the TMC and TMEC to predict the functions of proteins on three
      benchmarks. We show that our approaches perform better than recently proposed
      protein function prediction methods on composite and multiple kernels. The code,
      data sets used in this paper and supplemental material are available at
      https://sites.google.com/site/guoxian85/tmec.

PMID- 24334397
TI  - Temporal logics for phylogenetic analysis via model checking.
AB  - The need for general-purpose algorithms for studying biological properties in
      phylogenetics motivates research into formal verification frameworks. Researchers
      can focus their efforts exclusively on evolution trees and property
      specifications. To this end, model checking, a mature automated verification
      technique originating in computer science, is applied to phylogenetic analysis.
      Our approach is based on three cornerstones: a logical modeling of the evolution
      with transition systems; the specification of both phylogenetic properties and
      trees using flexible temporal logic formulas; and the verification of the latter
      by means of automated computer tools. The most conspicuous result is the
      inception of a formal framework which allows for a symbolic manipulation of
      biological data (based on the codification of the taxa). Additionally, different
      logical models of evolution can be considered, complex properties can be
      specified in terms of the logical composition of others, and the refinement of
      unfulfilled properties as well as the discovery of new properties can be
      undertaken by exploiting the verification results. Some experimental results
      using a symbolic model verifier support the feasibility of the approach. 

PMID- 24334398
TI  - Application of Dempster-Schafer method in family-based association studies.
AB  - In experiments designed for family-based association studies, methods such as
      transmission disequilibrium test require large number of trios to identify single
      nucleotide polymorphisms associated with the disease. However, unavailability of
      a large number of trios is the Achilles' heel of many complex diseases,
      especially for late-onset diseases. In this paper, we propose a novel approach to
      this problem by means of the Dempster-Shafer method. The simulation studies show
      that the Dempster-Shafer method has a promising overall performance, in
      identifying single-nucleotide polymorphisms in the correct association class, as
      it has 90 percent accuracy even with 60 trios. 

PMID- 24334399
TI  - Hamiltonian walks of phylogenetic treespaces.
AB  - We answer Bryant's combinatorial challenge on minimal walks of phylogenetic
      treespace under the nearest-neighbor interchange (NNI) metric. We show that the
      shortest path through the NNI-treespace of n-leaf trees is Hamiltonian for all n.
      That is, there is a minimal path that visits all binary trees exactly once, under
      NNI moves.

PMID- 24334400
TI  - Hierarchical clustering of high-throughput expression data based on general
      dependences.
AB  - High-throughput expression technologies, including gene expression array and
      liquid chromatography--mass spectrometry (LC-MS) and so on, measure thousands of
      features, i.e., genes or metabolites, on a continuous scale. In such data, both
      linear and nonlinear relations exist between features. Nonlinear relations can
      reflect critical regulation patterns in the biological system. However, they are
      not identified and utilized by traditional clustering methods based on linear
      associations. Clustering based on general dependences, i.e., both linear and
      nonlinear relations, is hampered by the high dimensionality and high noise level
      of the data. We developed a sensitive nonparametric measure of general dependence
      between (groups of) random variables in high dimensions. Based on this dependence
      measure, we developed a hierarchical clustering method. In simulation studies,
      the method outperformed correlation- and mutual information (MI)-based
      hierarchical clustering methods in clustering features with nonlinear
      dependences. We applied the method to a microarray data set measuring the gene
      expression in cell-cycle time series to show it generates biologically relevant
      results. The R code is available at http://userwww.service.emory.edu/~tyu8/GDHC. 

PMID- 24334401
TI  - Box jellyfish envenomation: case report of effective lemon and oil emulsion
      treatment.
AB  - Box jellyfish are highly venomous and numerous possible treatments for
      envenomation have already been reported in the published literature. The hand of
      a 55-year-old scuba diver was stung in the Gulf of Guinea resulting in two crops
      of coalescing vesicles with intense pain and lymphadenopathy. Traditional
      therapies such as hot water, cold packs and acetic acid were ineffective.
      Symptoms were rapidly relieved after the application of a lemon-oil emulsion
      balm. Treatments for jellyfish envenomation generally aim to either denature the
      jellyfish venom or prevent the discharge of the venom. Lemon-oil emulsion therapy
      has not yet been reported in the published literature but may be an economical
      and novel treatment for box jellyfish envenomation. 

PMID- 24334402
TI  - Clinico-epidemiological profile of seven adults with spotted fever from a
      tertiary care hospital in South India.
AB  - Spotted fever (SF), a tick-borne rickettsial infection, is being increasingly
      reported from mainly northern Indian states. A lack of awareness and confirmatory
      laboratory tests underestimate the incidence of this infection which, in India,
      is predominantly seen during the rainy season. Many patients diagnosed with viral
      exanthematous illnesses may be suffering from SF, which is treatable if detected
      early. There is very little data on SF in adults in southern India. We present
      seven patients with SF treated between January 2007 and January 2008 in a
      tertiary care hospital in South India. All presented during the rainy season,
      with rash (100%) and generalized oedema (71%) being the most common features.
      There was one death due to type I respiratory failure. Renal failure, shock,
      aseptic meningitis and hepatitis were other significant abnormalities detected in
      these patients. Clinicians need to be aware of SF and suspect it in appropriate
      patients. 

PMID- 24334403
TI  - Site-selective sulfurization of bromide-capped palladium nanocubes by polysulfide
      and the underlying mechanism.
AB  - This article describes site-selective sulfurization of Pd nanocubes capped by a
      monolayer of chemisorbed Br(-) ions. High-resolution transmission electron
      microscopy and high-angle annular dark-field scanning TEM observations showed
      that PdS was not formed until a certain quantity of polysulfide (S(x)(2-)) ions
      had been introduced (300 MUl, or 18.8 ppm in the final reaction solution). Spot
      energy dispersive x-ray spectroscopy and x-ray photoelectron spectroscopy
      analyses confirmed that the surface-chemisorbed Br(-) ions were completely
      substituted by S(x)(2-) ions before the initiation of the sulfurization reaction.
      In the presence of sufficient S(x)(2-) ions (>300 MUl or >18.8 ppm), PdS phase
      was selectively developed from the highly active corners, which then moved to the
      edges and finally towards the center until the entire nanocube was converted into
      PdS. The resultant PdS was found to be amorphous by electron microscopy and
      powder x-ray diffraction measurements. The amorphous structure of PdS facilitated
      the penetration and diffusion of S(x)(2-) species and thus acceleration of the
      reaction kinetics. As a result, the sulfurization of 13 nm Pd nanocubes was
      completed within a few minutes after the addition of adequate Na2Sx, leading to a
      much more severe poisoning effect, compared with other noble metals such as Ag,
      by sulfur.

PMID- 24334404
TI  - Multiphonon relaxation in rare-earth doped fluorozirconate-based glasses
      containing BaCl2 nanocrystals.
AB  - Nd3+-doped fluorozirconate-based glasses which contain hexagonal BaCl2
      nanocrystals are analyzed for their photoluminescence and multiphonon relaxation
      (MPR) properties. The MPR rates of various Nd3+ levels are obtained from time
      resolved spectroscopy using selective laser pulse excitation. The nonradiative
      decay rates are estimated from the difference between measured and calculated
      radiative decay rates as well as from the analysis of luminescence rise times.
      The MPR rates display an exponential dependence on the energy gap. Temperature
      dependent studies of the decay indicate that phonons of the BaCl2 nanocrystals
      are involved in the MPR processes leading to extremely low MPR rates which are
      orders of magnitude lower than in conventional oxide and halide glasses.
      Photoluminescence emissions,which are usually quenched by MPR, and enhanced
      radiative quantum efficiencies are found.

PMID- 24334405
TI  - [Update on a neglected tropical disease from the routine health information
      system in Cote d'Ivoire: Yaws, 2001 to 2011].
AB  - GOAL: The aim of this work is to describe the epidemiological characteristics of
      yaws in Cote d'Ivoire from 2001 to 2011, by data from the routine health
      information system. METHODS: This retrospective study was conducted from
      available health statistics from 2001 to 2011. RESULTS: From 2001 to 2006, the
      completeness of the regional health statistics was below 50%, while afterwards it
      exceeded 70% in all regions. The incidence rate of yaws in hospitals has declined
      from 44 to 14.8 per 100 000 population from 2002 to 2011. Two regional offices
      still reported highly endemic areas rates, four times higher than the national
      incidence. CONCLUSION: It appears that the action of donors has helped to improve
      the performance of the routine health information system in Cote d'Ivoire.
      Additionally, yaws remains endemic. The reduced incidence in hospitals is
      probably due to the reduction in their use by the population; the real population
      incidence is undoubtedly higher. A seroprevalence survey would make it possible
      to focus more accurately the upcoming mass treatment campaigns, under the aegis
      of WHO, to eradicate yaws.

PMID- 24334407
TI  - Adsorbate migration effects on continuous and discontinuous temperature-dependent
      transitions in the quality factors of graphene nanoresonators.
AB  - We perform classical molecular dynamics simulation to investigate the mechanisms
      underpinning the unresolved, experimentally observed temperature-dependent
      scaling transition in the quality factors of graphene nanomechanical resonators
      (GNMRs). Our simulations reveal that the mechanism underlying this temperature
      scaling phenomenon is the out-of-plane migration of adsorbates on GNMRs.
      Specifically, the migrating adsorbate undergoes frequent collisions with the
      GNMR, which strongly influences the resulting mechanical oscillation, and thus
      the quality factors. We also predict a discontinuous transition in the quality
      factor at a lower critical temperature, which results from the in-plane migration
      of the adsorbate. Overall, our work clearly demonstrates the strong effect of
      adsorbate migration on the quality factors of GNMRs. 

PMID- 24334406
TI  - PI3K/p110alpha inhibition selectively interferes with arterial thrombosis and
      neointima formation, but not re-endothelialization: potential implications for
      drug-eluting stent design.
AB  - BACKGROUND: Impaired re-endothelialization and stent thrombosis are a safety
      concern associated with drug-eluting stents (DES). PI3K/p110alpha controls
      cellular wound healing pathways, thereby representing an emerging drug target to
      modulate vascular homoeostasis after injury. METHODS AND RESULTS: PI3K/p110alpha
      was inhibited by treatment with the small molecule inhibitor PIK75 or a specific
      siRNA. Arterial thrombosis, neointima formation, and re-endothelialization were
      studied in a murine carotid artery injury model. Proliferation and migration of
      human vascular smooth muscle cell (VSMC) and endothelial cell (EC) were assessed
      by cell number and Boyden chamber, respectively. Endothelial senescence was
      evaluated by the beta-galactosidase assay, endothelial dysfunction by organ
      chambers for isometric tension. Arterial thrombus formation was delayed in mice
      treated with PIK75 when compared with controls. PIK75 impaired arterial
      expression and activity of tissue factor (TF) and plasminogen activator inhibitor
      1 (PAI-1); in contrast, plasma clotting and platelet aggregation did not differ.
      In VSMC and EC, PIK75 inhibited expression and activity of TF and PAI-1. These
      effects occurred at the transcriptional level via the RhoA signalling cascade and
      the transcription factor NFkB. Furthermore, inhibition of PI3K/p110alpha with
      PIK75 or a specific siRNA selectively impaired proliferation and migration of
      VSMC while sparing EC completely. Treatment with PIK75 did not induce endothelial
      senescence nor inhibit endothelium-dependent relaxations. In line with this
      observation, treatment with PIK75 selectively inhibited neointima formation
      without affecting re-endothelialization following vascular injury. CONCLUSION:
      Following vascular injury, PI3K/p110alpha inhibition selectively interferes with
      arterial thrombosis and neointima formation, but not re-endothelialization.
      Hence, PI3K/p110alpha represents an attractive new target in DES design.

PMID- 24334408
TI  - Vitamin D represses dentin matrix protein 1 in cementoblasts and osteocytes.
AB  - Calcium and phosphorus homeostasis is achieved by interplay among hormones,
      including 1,25(OH)2D3 (1,25D), parathyroid hormone, and fibroblast growth factor
      23 (FGF23), and their interactions with other proteins. For example, mutations in
      dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic
      rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D
      may be involved in modulating DMP-1 in an intermediary step. Murine cementoblasts
      (OCCM-30) and osteocyte-like cells (MLO-Y4 and MLO-A5), known to express DMP-1,
      were used to analyze effects of 1,25D on DMP-1 expression in vitro. DMP-1 mRNA
      levels decreased by 50% (p < .05) in the presence of 1,25D in all cell types,
      while use of a vitamin D receptor (VDR) agonist (EB1089) and antagonist (23S,25S)
      DLAM-2P confirmed that VDR pathway activation was required for this response.
      Further analysis showed that histone deacetylase recruitment was necessary, but
      neither protein kinase A nor C pathways were required. In conclusion, our results
      support the hypothesis that 1,25D regulates DMP-1 expression through a VDR
      dependent mechanism, possibly contributing to local changes in bone/tooth mineral
      homeostasis.

PMID- 24334410
TI  - Fusobacterium nucleatum activates the immune response through retinoic acid
      inducible gene I.
AB  - Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition
      receptor involved in the sensing of RNA viruses and the initiation of antiviral
      responses. Fusobacterium nucleatum, a Gram-negative anaerobic bacterium
      associated with periodontal disease, is capable of invading cells. We
      hypothesized that F. nucleatum's ability to invade cells allows the microorganism
      to activate the immune response through RIG-I. Bacterial invasion was found to be
      necessary for F. nucleatum-induced nuclear factor kappa B (NF-kappaB) activation.
      Following invasion of the human periodontal ligament fibroblast (PDLF), F.
      nucleatum was located in the cytosol. F. nucleatum infection led to an 80-fold
      increase in RIG-I expression. Silencing RIG-I in PDLF by siRNA led to a
      significant decrease of NF-kappaB activation and expression of proinflammatory
      genes. Additionally, F. nucleatum was able to secrete nucleic acids, and
      introduction of F. nucleatum RNA into PDLF led to a RIG-I-dependent activation of
      NF-kappaB. Our findings showed RIG-I to be involved in the recognition of F.
      nucleatum. The function of RIG-I is likely to be broad and not limited to sensing
      of viruses only. Hence, this receptor may play an important role in detecting
      invasive forms of oral pathogens and contribute to inflammation in periodontal
      tissues.

PMID- 24334411
TI  - Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic
      populations.
AB  - Inter-individual differences in genes for drug metabolising enzymes and drug
      transporters are important for understanding efficacy in drug therapy. These
      differences are important both for the timely estimation of the dosage that
      should be prescribed to a patient and for the detection of individuals who are
      prone to side effects from the drug at normal doses. This review summarises the
      literature concerning the gene variants within nine major drug metabolising
      enzymes and drug transporters (i.e., CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6,
      CYP2E1, CYP3A4, CYP3A5, and MDR-1) in the Middle European region. Notably,
      published data are not extensive, and most studies were performed on relatively
      low numbers of individuals. No country has a complete coverage of all genes. Two
      variants (C2677T/A and C3435T) within the multidrug resistance-1 (MDR-1) gene and
      variants within the CYP2C9 gene were analysed within most Slavic populations.
      Nevertheless, even from this incomplete coverage (where unexpectedly high
      variability was at times seen both between and within populations), it could be
      extrapolated that the variants within the drug metabolising enzyme genes are
      present in roughly the same frequencies as in neighbouring countries.

PMID- 24334409
TI  - Carbodiimide inactivation of MMPs and effect on dentin bonding.
AB  - The use of protein cross-linking agents during bonding procedures has been
      recently proposed to improve bond durability. This study aimed to use zymography
      and in situ zymography techniques to evaluate the ability of 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide (EDC) cross-linker to inhibit matrix
      metalloproteinase (MMP) activity. The hypotheses tested were that: (1) bonding
      procedures increase dentin gelatinolytic activity and (2) EDC pre-treatment
      prevents this enzymatic activity. The zymographic assay was performed on protein
      extracts obtained from dentin powder treated with Optibond FL or Scotchbond 1XT
      with or without 0.3M EDC pre-treatment. For in situ zymography, adhesive/dentin
      interfaces were created with the same adhesives applied to acid-etched dentin
      slabs pre-treated or not with EDC conditioner. Zymograms revealed increased
      expression of dentin endogenous MMP-2 and -9 after adhesive application, while
      the use of EDC as a primer inactivated dentin gelatinases. Results of in situ
      zymograpy showed that hybrid layers of tested adhesives exhibited intense
      collagenolytic activity, while almost no fluorescence signal was detected when
      specimens were pre-treated with EDC. The correlative analysis used in this study
      demonstrated that EDC could contribute to inactivate endogenous dentin MMPs
      within the hybrid layer created by etch-and-rinse adhesives. 

PMID- 24334412
TI  - Highlight: the 5th International Workshop on Septin Biology.

PMID- 24334413
TI  - The revised Lund-Malmo GFR estimating equation outperforms MDRD and CKD-EPI
      across GFR, age and BMI intervals in a large Swedish population.
AB  - BACKGROUND: The performance of creatinine-based glomerular filtration rate (GFR)
      estimating equations may vary in subgroups defined by GFR, age and body mass
      index (BMI). This study compares the performance of the Modification of Diet in
      Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration
      (CKD-EPI) equations with the revised Lund-Malmo equation (LM Revised), a new
      equation that can be expected to handle changes in GFR across the life span more
      accurately. METHODS: The study included 3495 examinations in 2847 adult Swedish
      patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of
      iohexol (median 52 mL/min/1.73 m2). Bias, precision [interquartile range (IQR)]
      and accuracy [percentage of estimates +/-10% (P10) and +/-30% (P30) of mGFR] were
      compared. RESULTS: The overall results of LM Revised/MDRD/CKD-EPI were: median
      bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m2, P10 40%/35%/35% and P30 84%/75%/76%.
      LM Revised was the most stable equation in terms of bias, precision and accuracy
      across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI
      overestimated mGFR in patients with decreased kidney function, young adults and
      elderly. All three equations overestimated mGFR and had low accuracy in patients
      with BMI <20 kg/m2, most pronounced among men. CONCLUSIONS: In settings similar
      to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due
      to its higher accuracy and more stable performance across GFR, age and BMI
      intervals.

PMID- 24334414
TI  - Imaging of musculoskeletal lymphoma.
AB  - Lymphoma of the musculoskeletal system involving the bone, muscle or skin is
      commonly due to secondary involvement from disseminated disease but can
      occasionally present as primary extranodal disease. Although radiological
      features are traditionally known to be non-specific, recognition of certain
      characteristics using summation of imaging modalities as well as knowledge of
      clinical features can help in making the diagnosis. Imaging also plays an
      integral role in treatment response assessments, especially via positron emission
      tomography/computed tomography functional imaging. 

PMID- 24334415
TI  - HapRice, an SNP haplotype database and a web tool for rice.
AB  - Genome-wide single nucleotide polymorphism (SNP) analysis is a promising tool to
      examine the genetic diversity of rice populations and genetic traits of
      scientific and economic importance. Next-generation sequencing technology has
      accelerated the re-sequencing of diverse rice varieties and the discovery of
      genome-wide SNPs. Notably, validation of these SNPs by a high-throughput
      genotyping system, such as an SNP array, could provide a manageable and highly
      accurate SNP set. To enhance the potential utility of genome-wide SNPs for
      geneticists and breeders, analysis tools need to be developed. Here, we
      constructed an SNP haplotype database, which allows visualization of the allele
      frequency of all SNPs in the genome browser. We calculated the allele frequencies
      of 3,334 SNPs in 76 accessions from the world rice collection and 3,252 SNPs in
      177 Japanese rice accessions; all these SNPs have been validated in our previous
      studies. The SNP haplotypes were defined by the allele frequency in each cultivar
      group (aus, indica, tropical japonica and temperate japonica) for the world rice
      accessions, and in non-irrigated and three irrigated groups (three variety
      registration periods) for Japanese rice accessions. We also developed web tools
      for finding polymorphic SNPs between any two rice accessions and for the primer
      design to develop cleaved amplified polymorphic sequence markers at any SNP. The
      'HapRice' database and the web tools can be accessed at
      http://qtaro.abr.affrc.go.jp/index.html. In addition, we established a core SNP
      set consisting of 768 SNPs uniformly distributed in the rice genome; this set is
      of a practically appropriate size for use in rice genetic analysis. 

PMID- 24334416
TI  - Microscopic origin of stereochemically active lone pair formation from orbital
      selective external potential calculations.
AB  - The nature of the stereochemically active lone pair has long been a matter for
      debate. Here, by application of our recently developed orbital selective external
      potential (OSEP) method, we have studied the microscopic mechanism of
      stereochemically active lone pairs in various compounds. The OSEP method allows
      us to shift the energy level of a specific atomic orbital, therefore is helpful
      to identify unambiguously the role of this orbital in the chemical and physical
      properties of the system we are interested in. Our numerical results, with
      compelling proofs, demonstrate that the on-site mixing of the cation valence s
      orbital with the nominally empty p orbitals of the same subshell is crucial to
      the formation of a lone pair, whereas the anion p orbital has only a small
      effect. Our detailed investigation of Sn and Pb monochalcogenides shows that
      structures of these systems have significant effects on lone pairs. In return,
      the formation of lone pairs, which can be controlled by our OSEP method, could
      result in structural instabilities of Sn and Pb monochalcogenides.

PMID- 24334417
TI  - Ultrafast and sensitive room temperature NH3 gas sensors based on chemically
      reduced graphene oxide.
AB  - Ultrafast and sensitive room temperature NH3 gas sensors based on chemically
      reduced graphene oxide (rGO) are demonstrated in this work. rGO, which was
      prepared via the reduction of graphene oxide by pyrrole, exhibited excellent
      responsive sensitivity and selectivity to ammonia (NH3) gas. The high sensing
      performance of these rGO sensors with resistance change as high as 2.4% and
      response time as fast as 1.4 s was realized when the concentration of NH3 gas was
      as low as 1 ppb. Furthermore, the rGO sensors could rapidly recover to their
      initial states with IR illumination. The devices also showed excellent
      repeatability and selectivity to NH3. These rGO sensors, with low cost, low
      power, and easy fabrication, as well as scalable properties, showed great
      potential for ultrasensitive detection of NH3 gas in a wide variety of fields. 

PMID- 24334418
TI  - [French naval physicians, surgeons, and pharmacists in the history of the thermal
      spas of Reunion].
AB  - Navy physicians, surgeons, and pharmacists, because of their knowledge of
      balneology and hydrotherapeutics in metropolitan France, played a key role in the
      history of the thermal waters of Reunion, discovered in the 19(th) century in
      Mafate, Cilaos, and Salazie. 

PMID- 24334419
TI  - Effect of intergenerational and intragenerational support on perceived health of
      older adults: a population-based analysis in rural China.
AB  - BACKGROUND: The family, together with the individual and society, and the state
      and market are the three pillars of well-being and social security over the life
      course, with responsibility for the health of older adults. OBJECTIVE: The aim of
      current study was to explore the effect of intergenerational and
      intragenerational support on perceived health of older adults. METHODS: A cross
      sectional survey with 64.36% (1318/2048) response rate was conducted door to door
      in rural China with a sample of 1318 individuals aged 60 years and older. There
      were three sets of independent variables: intergenerational support from children
      as well as intragenerational spousal support and intragenerational sibling
      support, sociodemographic variables, and behaviour variables. Multiple logistic
      regression analysis was used to analyse the influence of family member support on
      physical and psychological health. RESULTS: After adjusting for potential
      confounding variables (sociodemographic variables and behaviour variables), it
      was observed that intergenerational support from children had a significant
      effect on the self-rated physical health and psychological health of older adults
      [odds ratios (OR) = 1.48, 95% confidence interval (CI): 1.10-2.00; OR = 1.82, 95%
      CI: 1.36-2.44, respectively]. However, intragenerational support from spouse and
      siblings was not significant. CONCLUSION: The importance of intergenerational
      support from children would suggest that family practice and health-related
      policy of older adults may need to be extended to their children. With the rapid
      development of global population movements, family practices need to pay
      attention to the changes of family support among migrant families.

PMID- 24334420
TI  - Acceptability of NHS 111 the telephone service for urgent health care: cross
      sectional postal survey of users' views.
AB  - BACKGROUND: In 2010, a new telephone service, NHS 111, was piloted to improve
      access to urgent care in England. A unique feature is the use of non-clinical
      call takers who triage calls with computerized decision support and have access
      to clinical advisors when necessary. Aim. To explore users' acceptability of NHS
      111. DESIGN: Cross-sectional postal survey. SETTING: Four pilot sites in England.
      METHOD: A postal survey of recent users of NHS 111. RESULTS: The response rate
      was 41% (1769/4265), with 49% offering written comments (872/1769). Sixty-five
      percent indicated the advice given had been very helpful and 28% quite helpful.
      The majority of respondents (86%) indicated that they fully complied with advice.
      Seventy-three percent was very satisfied and 19% quite satisfied with the service
      overall. Users were less satisfied with the relevance of questions asked, and the
      accuracy and appropriateness of advice given, than with other aspects of the
      service. Users who were autorouted to NHS 111 from services such as GP out-of
      hours services were less satisfied than direct callers. CONCLUSION: In pilot
      services in the first year of operation, NHS 111 appeared to be acceptable to the
      majority of users. Acceptability could be improved by reassessing the necessity
      of triage questions used and auditing the accuracy and appropriateness of advice
      given. User acceptability should be viewed in the context of findings from the
      wider evaluation, which identified that the NHS 111 pilot services did not
      improve access to urgent care and indeed increased the use of emergency ambulance
      services.

PMID- 24334421
TI  - Non-invasive ECG-triggered 2D TOF MR angiography of the pelvic and leg arteries
      in an open 1.0-tesla high-field MRI system in comparison to conventional DSA.
AB  - OBJECTIVES: A non-contrast-enhanced 2D time-of-flight magnetic resonance
      angiography (TOF-MRA) protocol was compared with the gold standard of planar
      digital subtraction angiography (DSA) by calculating correlations of vessel
      diameters. METHODS: A total of 1134 vascular diameters in 81 corresponding sites
      were prospectively measured by TOF-MRA and DSA in seven patients (four women,
      three men; mean age, 68 years). For a total of 162 vascular segments per patient,
      81 Spearman's rho correlation coefficients were calculated, consolidated to 41
      due to consideration of symmetry (right/left), and assessed by correlation
      quality. RESULTS: In the 41 consolidated segments, correlations were good, very
      good, and excellent in 25 segments (n=10>0.5, n=4>0.7, and n=11>0.8), moderate to
      poor in seven segments (n=4>0.3 and 0<n=3<=0.3), without in two, inverse in
      three, and nonmeasurable in four segments. Correlations were best for the main
      arteries above the knee, and these arteries were most consistently visualized.
      CONCLUSION: The TOF-MRA protocol presented here can be performed in an open 1.0-T
      MRI system in 60-90 min. Visualization is degraded when the target artery leaves
      the plane orthogonal to the imaging plane (1) or signal yield is poor due to
      small caliber (2).

PMID- 24334422
TI  - Risk factors for pregnancy-associated venous thromboembolism: a review.
AB  - AIM: To critically evaluate current understanding of risk factors for pregnancy
      associated venous thromboembolism (VTE) and to describe underlying molecular
      mechanisms. METHODS: A literature search was undertaken using the national
      library of medicine PubMed database. The search terms used were "pregnancy" and
      "venous thromboembolism". Following exclusion of unsuitable data sources, studies
      were identified that described specific risk factors for pregnancy-associated VTE
      and suggested possible underlying molecular mechanisms. Adjusted odds ratios and
      incident rate ratios for these specific risk factors were identified in each
      study and tabulated. RESULTS: A series of mainly retrospective cohort and case
      control studies over the past two decades have reported specific risk factors for
      pregnancy-associated VTE. Recent published literature has highlighted the
      interaction between commonly occurring risk factors, particularly the potential
      for a multiplicative effect on overall VTE risk, and have led to improvements in
      our understanding of the molecular mechanisms underlying these risk factors.
      CONCLUSION: Mortality from pregnancy associated VTE continues despite prevention
      strategies. A detailed understanding of specific risk factors, their interactions
      and underlying molecular mechanisms is required to identify women at highest risk
      and to guide development of thromboprophylaxis strategies.

PMID- 24334423
TI  - Mother knows best? Comparing primiparous parturients' expectations and
      predictions with actual birth outcomes.
AB  - OBJECTIVE: The literature provides no clear evidence linking maternal
      optimism/pessimism to birth outcomes. Our objective was to determine whether
      maternal expectations and predictions regarding mode of delivery and epidural
      anesthesia aligned with birth outcomes. METHODS: Primiparous, low-risk pregnant
      women at term filled in questionnaires in which they rated their chances of a
      vaginal delivery (VD) or a cesarean section (CS), and their intention to receive
      epidural anesthesia. Their responses were compared to actual outcomes. RESULTS:
      Pre-birth perceptions of odds of delivery by a CS were significantly higher
      (P=0.04) among women who eventually had a vacuum extraction (VE) or CS as a
      result of an arrest disorder, compared with women who had a VD and those who had
      a CS or a VE due to non-reassuring fetal heart monitor. Intention to receive
      epidural anesthesia was significantly lower (P<0.001) among women who gave birth
      without it. CONCLUSION: The pessimistic pre-birth perceptions of women of high
      odds for a CS may be related to an increased risk of arrest disorders of labor.
      However, the prenatal assessments of primiparous women are poor predictors of
      their demand for epidural anesthesia during labor. Larger-scale studies to
      determine whether pre-partum psychological interventions may contribute to the
      process of labor and improve obstetric outcomes are warranted.

PMID- 24334424
TI  - Chemerin concentrations in maternal and fetal compartments: implications for
      metabolic adaptations to normal human pregnancy.
AB  - OBJECTIVES: Chemerin, a novel adipocytokine, has been implicated in major
      metabolic and inflammatory processes. Study aims were to determine whether
      circulating maternal chemerin concentration (1) differs between pregnant and non
      pregnant women, (2) changes as a function of gestational age, and (3) correlates
      with maternal insulin resistance. In addition, we investigated which compartment,
      maternal, fetal or placental, is the source of chemerin in maternal circulation.
      METHODS: The study included three groups: Non-pregnant (n=18), pregnant women in
      the first trimester (n=19) and pregnant women in the third trimester (n=33).
      Chemerin was measured in cord blood and in maternal serum samples taken before
      and after delivery. Chemerin mRNA expression was evaluated in fetal and human
      adult tissues. RESULTS: Chemerin serum concentration was significantly higher in
      pregnant women in the third trimester than in non-pregnant and pregnant women in
      the first trimester. Chemerin concentration positively correlated with body mass
      index (BMI) and insulin resistance. Antenatal chemerin concentration was
      significantly lower than that during the postpartum period. Neonatal chemerin did
      not correlate with maternal one. Chemerin mRNA expression was abundant in fetal
      and adult liver and omental fat, but relatively low in placenta. CONCLUSIONS:
      Chemerin is increased during normal gestation and is associated with maternal BMI
      and insulin resistance. Maternal tissues, possibly liver and adipose tissue,
      contribute to the increased maternal chemerin concentration.

PMID- 24334425
TI  - Cytomegalovirus infection among infants in California neonatal intensive care
      units, 2005-2010.
AB  - AIM: To assess the burden of congenital and perinatal cytomegalovirus (CMV)
      disease among infants hospitalized in neonatal intensive care units (NICUs).
      METHODS: CMV infection was defined as a report of positive CMV viral culture or
      polymerase chain reaction at any time since birth in an infant hospitalized in a
      NICU reporting to California Perinatal Quality Care Collaborative during 2005
      2010. RESULTS: One hundred and fifty-six (1.7 per 1000) infants were reported
      with CMV infection, representing an estimated 5% of the expected number of live
      births with symptomatic CMV disease. Prevalence was higher among infants with
      younger gestational ages and lower birth weights. Infants with CMV infection had
      significantly longer hospital stays and 14 (9%) died. CONCLUSIONS: Reported
      prevalence of CMV infection in NICUs represents a fraction of total expected
      disease burden from CMV in the newborn period, likely resulting from
      underdiagnosis and milder symptomatic cases that do not require NICU care. More
      complete ascertainment of infants with congenital CMV infection that would
      benefit from antiviral treatment may reduce the burden of CMV disease in this
      population.

PMID- 24334426
TI  - Gestational weight gain according to number of fetuses in Japanese women.
AB  - AIM: It is unknown whether weekly maternal weight gain differs between Japanese
      women with singleton, twin, and triplet pregnancies. METHODS: Gestational weight
      gain defined as net weight gain during pregnancy was analyzed in 135,036 pregnant
      Japanese women, including 128,838 with singletons, 5573 with twins, and 132 with
      triplets, who gave birth at >=22 weeks of gestation between 2007 and 2009. Weekly
      weight gain was defined as follows: gestational weight gain/[gestational week
      (GW) at Delivery-2]. RESULTS: Length of gestation (weeks, mean+/-SD) decreased
      significantly (38.2+/-2.6, 35.3+/-3.0, and 32.7+/-2.8) with increasing number of
      fetuses, while overall gestational weight gain (kg) was significantly smaller in
      women with singletons than in those with either twins or triplets (9.6+/-4.4 vs.
      10.9+/-4.8 or 10.9+/-5.2, respectively). Thus, weekly maternal weight gain
      (kg/week) increased significantly with increasing number of fetuses (0.26+/-0.12,
      0.33+/-0.13, and 0.35+/-0.16). Among women with delivery at or after GW 34,
      difference in gestational weight gain (kg) was prominent between the three groups
      (9.8+/-4.4, 11.4+/-4.7, and 13.0+/-5.1 for singleton, twin, and triplet
      pregnancies, respectively, P<0.001 between any two groups). CONCLUSIONS: Weekly
      maternal weight gain increases with increasing number of fetuses. Our figures may
      be useful for advising Japanese women with multifetal pregnancies regarding
      gestational weight gain.

PMID- 24334427
TI  - Placental chorioangioma: literature review.
AB  - Placental chorioangioma is the most common benign non-trophoblastic tumor of the
      placenta. It is derived from primitive chorionic mesenchyme and is typically
      vascular. Placenta chorioangiomas occur in approximately 1% of pregnancies. Most
      placental chorioangiomas are small and are not clinically important. However,
      those measuring more than 4-5 cm in diameter may be associated with maternal and
      fetal complications. Early diagnosis, close prenatal surveillance and appropriate
      intervention may prevent severe complications and perinatal mortality caused by
      chorioangioma. Here we review the incidence, prenatal diagnosis, complications,
      the pathophysiological mechanisms of maternal and fetal complications, and the
      therapeutic possibilities in pregnancies complicated by placental chorioangiomas.

PMID- 24334428
TI  - Peripartum thromboprophylaxis before and after implementation of a uniform
      heparin protocol.
AB  - AIM: The objective of this study was to assess the utilization of postpartum
      thromboprophylaxis with heparin in patients according to the Royal College of
      Obstetrics and Gynaecology Green-Top guidelines after change from an opt-in to an
      opt-out policy for health care providers ordering heparin thromboprophylaxis
      after cesarean delivery. STUDY DESIGN: The present study is a retrospective
      review of 500 consecutive births at one academic institution before and after
      implementation of a uniform thromboprophylaxis policy with heparin for all
      cesarean deliveries. An "opt-out" policy for ordering physicians was implemented
      by automatically defaulting to order heparin in the electronic order set used
      after cesarean delivery. RESULTS: Cesarean delivery rates were similar during
      both time periods. Heparin thromboprophylaxis was indicated in 99.6% of the
      cesarean delivery population before implementation and 94.5% after
      implementation. Prior to implementation only 5.7% received thromboprophylaxis
      compared to 96.1% after implementation, P<0.0001. CONCLUSION: An opt-out heparin
      thromboprophylaxis policy improves compliance with thromboprophylaxis guidelines
      compared to an opt-in policy. Institutions should consider opt-out heparin
      thromboprophylaxis policies after cesarean deliveries to improve compliance with
      recommendations.

PMID- 24334429
TI  - Evaluation of a novel placental alpha microglobulin-1 (PAMG-1) test to predict
      spontaneous preterm delivery.
AB  - OBJECTIVE: The PartoSure time-to-delivery (TTD) test (AmniSure International,
      Boston, MA, USA) is a newly available bedside test for the prediction of time to
      spontaneous preterm delivery via the detection of placental alpha microglobulin
      1. The objective of this study was to determine the efficacy of the test in
      predicting imminent delivery in 7 or 14 days from the time of testing. METHODS:
      The study population consisted of 101 consecutively recruited pregnant women with
      singleton pregnancies between 20+0 and 36+6 weeks of gestation with symptoms of
      preterm labor, clinically intact amniotic membranes, and minimal cervical
      dilatation (<=3 cm). The PartoSure TTD test was performed on these patients and
      the test-to-spontaneous-delivery interval was calculated. RESULTS: The PartoSure
      TTD test predicted spontaneous preterm delivery within 7 days with 90.0%
      sensitivity, 93.8% specificity, 97.4% negative predictive value (NPV), and 78.3%
      positive predictive value (PPV). The test predicted spontaneous preterm delivery
      within 14 days with 80% sensitivity, 96.1% specificity, 93.6% NPV, and 87.0% PPV.
      CONCLUSION: A positive PartoSure TTD test in patients presenting with symptoms of
      preterm labor, intact membranes, and minimal cervical dilatation (<=3 cm)
      indicated spontaneous preterm delivery will occur within 7 days with a high
      degree of accuracy. A negative result indicated that spontaneous preterm delivery
      within 14 days is highly unlikely.

PMID- 24334430
TI  - Aldosterone measurement with LiaisonXL automated system: remarks about reference
      range.

PMID- 24334431
TI  - Routine use of the Ion Torrent AmpliSeqTM Cancer Hotspot Panel for identification
      of clinically actionable somatic mutations.
AB  - BACKGROUND: Somatic mutation analysis is standard of practice for solid tumors in
      order to identify therapeutic sensitizing and resistance mutations. Our
      laboratory routinely performed standalone PCR-based methods for mutations in
      several genes. Rapid discovery and introduction of new therapeutics has demanded
      additional genomic information for adequate management of the cancer patient. We
      evaluated a next generation sequencing assay, the Ion Torrent AmpliSeq Cancer
      Hotspot Panelv2 (CHPv2), capable of identifying multiple somatic mutations in 50
      genes in a single assay. METHODS: Accuracy, precision, limit of detection, and
      specificity were evaluated using DNA from well-characterized cell lines,
      genetically engineered cell lines fixed and embedded in paraffin, and previously
      tested mutation positive or negative, formalin-fixed, paraffin-embedded (FFPE)
      tissues. Normal kidney, tonsil and colon FFPE tissues were used as controls.
      RESULTS: Accuracy studies showed 100% concordance in each patient sample between
      previous PCR results and the corresponding variants identified using the Ion
      Torrent panel. Precision studies gave consistent results when libraries were
      prepared from the same original DNA and were run on multiple 316 chips. The limit
      of detection was determined to be 5% for single nucleotide variants (SNVs) and
      20% for insertions and deletions (indels). Specificity studies using normal FFPE
      tissue previously tested by PCR methods were also 100%. CONCLUSIONS: We have
      evaluated the performance of the AmpliSeq Cancer Panel Hotspotv2 and show that it
      is suitable for clinical testing. This next generation sequencing panel has
      allowed the laboratory to consolidate a broader range of molecular oncology
      testing to a single platform and single assay.

PMID- 24334432
TI  - Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000
      patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial
      Fibrillation information from implanted devices).
AB  - OBJECTIVE: The aim of this study was to assess the association between maximum
      daily atrial fibrillation (AF) burden and risk of ischaemic stroke. BACKGROUND:
      Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a
      comprehensive measure of AF burden. DESIGN, SETTING, AND PATIENTS: A pooled
      analysis of individual patient data from five prospective studies was performed.
      Patients without permanent AF, previously implanted with CIEDs, were included if
      they had at least 3 months of follow-up. A total of 10 016 patients (median age
      70 years) met these criteria. The risk of ischaemic stroke associated with pre
      specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively)
      was assessed. RESULTS: During a median follow-up of 24 months, 43% of 10 016
      patients experienced at least 1 day with at least 5 min of AF burden and for them
      the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3
      14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants
      at baseline demonstrated that AF burden was an independent predictor of ischaemic
      stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated
      with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22
      3.64, P = 0.008). CONCLUSIONS: Device-detected AF burden is associated with an
      increased risk of ischaemic stroke in a relatively unselected population of CIEDs
      patients. This finding may add to the basis for timely and clinically appropriate
      decision-making on anticoagulation treatment.

PMID- 24334434
TI  - [Analysis of the healthcare service decentralization process in Cote d'Ivoire].
AB  - The decentralization of healthcare services is becoming increasingly important in
      strategies of public sector management. This concept is analyzed from various
      points of view, including legal, economic, political, and sociological. Several
      typologies have been proposed in the literature to analyze this decentralization
      process, which can take different forms ranging from simple deconcentration to
      more elaborate devolution. In some instances, decentralization can be analyzed by
      the degree of autonomy given to local authorities. This article applies these
      typologies to analyze the healthcare system decentralization process in Cote
      d'Ivoire. Special attention is paid to the new forms of community healthcare
      organizations. These decentralized structures enjoy a kind of autonomy, with
      characteristics closer to those of devolution. The model might serve as an
      example for population involvement in defining and managing healthcare problems
      in Cote d'Ivoire. We end with proposals for the improvement of the process. 

PMID- 24334433
TI  - [(18)F]Fluorodeoxyglucose-positron emission tomography screening for lung cancer:
      a systematic review and meta-analysis.
AB  - RATIONALE AND OBJECTIVES: Although low-dose computed tomography (CT) is a
      recommended modality for lung cancer screening in high-risk populations, the role
      of other modalities, such as [(18)F]fluorodeoxyglucose-positron emission
      tomography (PET), is unclear. We conducted a systematic review to describe the
      role of PET in lung cancer screening. MATERIALS AND METHODS: A systematic review
      was conducted by reviewing primary studies focusing on PET screening for lung
      cancer until July 2012. Two independent reviewers identified studies that were
      compatible for inclusion/exclusion criteria. The analysis was restricted to
      English and included studies published since 2000. A descriptive analysis was
      used to summarize the results, and the pooled diagnostic performance of selective
      PET screening was calculated by weighted average using individual sample sizes.
      RESULTS: Among the identified studies (n = 3497), 12 studies were included for
      analysis. None of the studies evaluated the efficacy of primary PET screening
      specific to lung cancer. Eight studies focused on primary PET screening for all
      types of cancer; the detection rates of lung cancer were low. Four studies
      reported evidence of lung cancer screening programs with selective PET, in which
      the estimated pooled sensitivity and specificity was 83% and 91%, respectively.
      CONCLUSIONS: The role of primary PET screening for lung cancer remains unknown.
      However, PET has high sensitivity and specificity as a selective screening
      modality. Further studies must be conducted to evaluate the use of PET or
      PET/computed tomography screening for high-risk populations, preferably using
      randomized trials or prospective registration. ADVANCES IN KNOWLEDGE: Our meta
      analysis indicates that PET has high sensitivity and specificity as a selective
      screening modality.

PMID- 24334435
TI  - Type 1 diabetes-associated TLR responsiveness of oral epithelial cells.
AB  - In type 1 diabetes (T1D), a Toll-like receptor (TLR)-hyper-inflammatory monocytic
      phenotype has been implicated as a mechanism of exacerbated tissue destruction.
      Other cells of the periodontium, including oral epithelial cells (OECs), express
      innate immune receptors, including TLRs. To delineate the TLR responses of OECs
      derived from T1D participants and to determine effects of the anti-inflammatory
      agent triclosan on the TLR-hyper-inflammatory phenotype, primary human OECs from
      individuals with T1D and diabetes-free individuals were stimulated with TLR
      ligands in the presence and/or absence of triclosan. The expression of pro
      inflammatory cytokines and micro-RNAs (miRNAs) was evaluated. While the
      repertoire of TLRs expressed by OECs is similar to that expressed by macrophages
      (M), the relative amounts and ratios are significantly different. OECs
      demonstrate a TLR-response profile similar to that of M, yet attenuated. OECs
      have a unique response to P. gingivalis LPS, where miR146a and miR155 play a
      regulatory role in responsiveness. OECs from T1D participants are TLR-hyper
      responsive, due to dysregulated induction of miR146a and miR155, which is
      abrogated by pre-treatment with triclosan. The aberrant TLR-activation of OECs in
      T1D has the potential to contribute to excessive soft- and hard-tissue
      destruction. Importantly, triclosan's anti-inflammatory property is effective in
      abrogating TLR-induced OEC hyperactivity.

PMID- 24334436
TI  - Transdermal gelation of methacrylated macromers with near-infrared light and gold
      nanorods.
AB  - Injectable hydrogels provide locally controlled tissue bulking and a means to
      deliver drugs and cells to the body. The formation of hydrogels in vivo may
      involve the delivery of two solutions that spontaneously crosslink when mixed,
      with pH or temperature changes, or with light (e.g., visible or ultraviolet).
      With these approaches, control over the kinetics of gelation, introduction of the
      initiation trigger (e.g., limited penetration of ultraviolet light through
      tissues), or alteration of the material physical properties (e.g., mechanics) may
      be difficult to achieve. To overcome these limitations, we used the interaction
      of near-infrared (NIR) light with gold nanorods (AuNRs) to generate heat through
      the photothermal effect. NIR light penetrates tissues to a greater extent than
      other wavelengths and provides a means to indirectly initiate radical
      polymerization. Specifically, this heating coupled with a thermal initiator (VA
      044) produced radicals that polymerized methacrylated hyaluronic acid (MeHA) and
      generated hydrogels. A range of VA-044 concentrations changed the gelation time,
      yielding a system stable at 37  degrees  C for 22 min that gels quickly (~3 min)
      when heated to 55  degrees  C. With a constant irradiation time (10 min) and
      laser power (0.3 W), different VA-044 and AuNR concentrations tuned the
      compressive modulus of the hydrogel. By changing the NIR irradiation time we
      attained a wide range of moduli at a set solution composition. In vivo mouse
      studies confirmed that NIR laser irradiation through tissue could gel an injected
      precursor solution transdermally.

PMID- 24334437
TI  - Effect of size reduction on the structural and magnetic order in LaMnO(3+delta)
      (delta ~ 0:03) nanocrystals: a neutron diffraction study.
AB  - We report a structural transition from the orthorhombic to the rhombohedral phase
      upon size reduction in nanocrystalline LaMnO(3+delta) (delta ~ 0:03) as revealed
      through neutron diffraction studies. The transition occurs when the average
      particle (crystallite) size is taken below ~50 nm without change of delta, which
      is fixed at around 0.03 as measured by a number of characterization tools. The
      change in the crystallographic structure is accompanied by a change in the
      magnetic order, where the canted antiferromagnetic order with moments in the
      basal (ab) plane for the bulk changes to collinear ferromagnetic order with spins
      along the c-axis for the nanocrystals. The spontaneous ferromagnetic moment ~3
      MU(B) and the transition temperature of 260 K in LaMnO(3+delta) nanocrystals are
      similar to those found in La0:67Ca0:33MnO3 which has a much higher Mn(4+)
      content. The likely origin is traced to change in magnetic exchange interactions
      due to change in Mn-O bond lengths which become almost identical in the MnO6
      octahedron in the rhombohedral structure in the absence of Jahn-Teller
      distortion. The study provides an example of structural and magnetic phase
      transition driven purely by size reduction and with no change in the chemical
      constituents.

PMID- 24334438
TI  - Template synthesis of single-phase delta(3)-MoN superconducting nanowires.
AB  - We demonstrate a new and effective method of producing single-phase
      superconducting delta3-MoN nanowires from bundled Mo6SyIz (8.2 <= y + z <= 10)
      nanowire templates in the presence of ammonia gas. Magnetic susceptibility and
      electrical resistance measurements confirm single-phase material synthesis.
      Measurements of four-contact resistance on single wires with diameters above 100
      nm in a magnetic field are used to determine the critical field, while diameter
      dependence and magnetization measurements are used to investigate the homogeneity
      of the nanowires. 

PMID- 24334440
TI  - [Integrated screening for HIV, syphilis, and toxoplasmosis among pregnant women
      in the Central African Republic].
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of syphilis and
      toxoplasmosis infection in pregnant women in the Central African Republic who
      were and were not HIV-infected, in the framework of HIV surveillance. METHODS:
      This case-control study included 270 HIV(+) and 217 HIV(-) pregnant women among 4
      750 women who attended prenatal-care clinics throughout the Central African
      Republic from November 2011 through January 2012. Blood specimens were collected
      and serological evidence of HIV1/2 was analyzed by ELISA1 and ELISA2. The
      Toxoplasma gondii antibody was detected with the Toxo-Hai Fumouze((r)) diagnostic
      kit. A VDRL test was performed to screen for syphilis in all study participants.
      RESULTS: Of the 434 samples tested, 33 (7.60%) were positive for syphilis: 21
      (9.7%) among HIV(+) and 12 (5.5%) among HIV(-) women (p = 0.1031); 221 (50.90%)
      were positive for toxoplasmosis: 117 (53.9%) among HIV(+) and 104 (47.9%) among
      HIV(-) women (p = 0, 2119). Coinfection with HIV, syphilis, and toxoplasmosis was
      found in 6.00%. No association was found between coinfection and age, parity, and
      residence area. The rate of syphilis infection was very high in pregnant women
      living in rural areas (ORcrude = 4.37; 95% CI = 2,11, 9.05). CONCLUSION: This
      study showed a high prevalence of toxoplasmosis and syphilis in pregnant women in
      the Central African Republic, regardless of their HIV infection status. Sexually
      transmitted infections (STIs) are common in pregnant women living in rural areas.
      It may be appropriate to include routine serological screening tests to determine
      of toxoplasmosis, syphilis and HIV in pregnant women in this country.

PMID- 24334441
TI  - Influence of beta-linkages on the morphology and performance of DArP P3HT-PC61BM
      solar cells.
AB  - Direct arylation polymerization (DArP) has emerged as a greener and more atom
      efficient alternative to Stille polymerization. Despite the attractiveness of
      this method, DArP is known to produce beta-linkages in polymers, which have beta
      protons available for activation. Here, we report the influence of the beta
      defect content in DArP poly(3-hexylthiophene) (P3HT) on the performance of bulk
      heterojunction solar cells and the morphology of pristine polymers and their
      blends with PC61BM in thin films and compare with Stille P3HT containing 0% beta
      defects as a reference point. The optical and electrochemical properties as well
      as the hole mobilities of pristine polymers remain virtually the same when the
      amount of beta-defects is limited to 0.75% or lower, as evidenced by UV-visible
      absorption spectra, cyclic voltammetry and space-charge-limited current (SCLC)
      mobility measurements. However, an increase of beta-defect concentration to 1.41%
      significantly affects the oxidation onset, UV-visible absorption profile and hole
      mobility of P3HT. The key result of this study is that the photovoltaic
      performance of DArP P3HT with 0% beta-defects is remarkably close to that of
      Stille P3HT, whereas the performance of DArP P3HT with 0-0.75% beta-defects does
      not differ dramatically from that of Stille P3HT and could potentially be
      improved upon by individual optimization of the processing conditions. 

PMID- 24334439
TI  - Progress on the diagnosis and evaluation of brain tumors.
AB  - Brain tumors are one of the most challenging disorders encountered, and early and
      accurate diagnosis is essential for the management and treatment of these tumors.
      In this article, diagnostic modalities including single-photon emission computed
      tomography, positron emission tomography, magnetic resonance imaging, and optical
      imaging are reviewed. We mainly focus on the newly emerging, specific imaging
      probes, and their potential use in animal models and clinical settings. 

PMID- 24334442
TI  - Oxidation states and quality of upper interfaces in magnetic tunnel junctions:
      oxygen effect on crystallization of interfaces.
AB  - In this study, we have deposited an 57Fe sensor layer at the upper interface,
      i.e. the interface between the oxide barrier and the upper electrode in selected
      magnetic tunnel junctions (MTJs), in order to perform nuclear resonant scattering
      with the aim of obtaining direct information on the magnetic properties and
      quality of this interface. This is a unique approach as it makes use of this
      powerful technique to give information at the atomic level, and specifically from
      the interface where the sensor layer is deposited. By varying sample tunnel
      barrier thicknesses and oxidation times in the preparation of this barrier, we
      have observed that longer oxidation time results in not only an increase of the
      magnetic hyperfine fields, but also causes an interesting crystallization and
      smoothing of the interface. We also observed that boron atoms diffuse away from
      the lower part of the upper FeCoB electrode toward the capping layer. An
      important observation, which has a crucial effect in tunnel magnetoresistance
      values, is the absence of any magnetically dead FeO layer at the interface.
      Another finding is that the deposition of Fe on MgO is much smoother than the
      deposition of MgO on Fe.

PMID- 24334443
TI  - The suitability of corneas stored by organ culture for penetrating keratoplasty
      and influence of donor and recipient factors on 5-year graft survival.
AB  - PURPOSE: To determine the impact of donor factors on the suitability of corneas
      stored by organ culture for penetrating keratoplasty (PK) and the influence of
      donor and recipient factors on 5-year survival of first PK. METHODS: Logistic
      regression analyses were carried out to determine the influence of donor factors
      on, respectively, the risk of microbial contamination during organ culture, the
      suitability of corneas for PK (endothelial cell density >= 2200 cells/mm(2)), and
      the quality of corneas (endothelial cell density >= 2500 cells/mm(2)). Only one
      cornea, randomly selected, from each donor was included in these analyses. A Cox
      regression analysis was used to determine the influence of donor and recipient
      factors on 5-year PK survival. RESULTS: Risk of contamination (n = 8317): Causes
      of donor death including infection, respiratory disease, and cancer all increased
      the risk of contamination during organ culture (P < 0.0001). Suitability for PK
      and endothelial quality (n = 7107): Donor age (P < 0.0001) and storage time in
      organ culture (P < 0.0001) were the principal factors affecting suitability and
      quality. Death to enucleation and enucleation to processing times had little
      influence. Corneas from organ donors were more likely to be suitable for PK (P =
      0.0003). Five-year graft survival (n = 3014): Graft survival was dominated by the
      indication for PK (P < 0.0001). Allograft rejection was also a major risk factor
      for failure (P < 0.0001). The only donor factor affecting survival was sex (P =
      0.008). CONCLUSIONS: Donor age and storage time but not postmortem times
      influenced the suitability of corneas for PK. The indication for PK and other
      recipient factors were the main predictors of graft failure.

PMID- 24334444
TI  - The effects of estrogen and androgen on tear secretion and matrix
      metalloproteinase-2 expression in lacrimal glands of ovariectomized rats.
AB  - PURPOSE: Previous studies have shown that ovariectomy (OVX) induces lacrimal
      gland regression and that androgens are implicated. This study explored the
      effects of estrogen and androgen on tear secretion and matrix metalloproteinase 2
      (MMP-2) expression in lacrimal glands of ovariectomized rats. METHODS: Sixty-four
      adult female Wistar rats were randomly divided into three groups (control, sham
      operated, and OVX). Bilateral OVX was performed in the OVX group. After 5 months,
      the OVX group was further divided into six subgroups receiving topical ophthalmic
      or systemic treatment with corn oil vehicle, estradiol, or testosterone for 6
      weeks. Schirmer test (SIT), assessment of tear film breakup time (BUT), corneal
      fluorescein staining, and measurement of estradiol and testosterone levels were
      performed before OVX and 1, 2, 3, 4, and 5 months after OVX, as well as after 6
      weeks of treatment. Lacrimal glands were assessed for MMP-2 mRNA and protein
      expression. RESULTS: The mean (SD) tear film BUT decreased from 10.53 (0.79) to
      9.98 (1.00) seconds (P < 0.01) in the first month after OVX, and the mean (SD)
      SIT result decreased by 50% from 7.32 (1.61) to 3.39 (1.15) mm (P < 0.01) in the
      third month after OVX. The mean (SD) corneal fluorescein staining score increased
      from 0.35 (0.11) to 6.02 (1.34) (P < 0.05) in the fourth month after OVX. The
      values increased or decreased in parallel with the time course (P < 0.01). In
      serum, ovariectomy resulted in a mean (SD) decline in estradiol levels from 44.38
      (9.78) to 23.00 (3.78) pg/mL (P < 0.01), and the mean (SD) testosterone levels
      decreased from 2.42 (0.26) to 1.87 (0.15) ng/mL (P < 0.05). The mean (SD)
      estradiol level was elevated to 35.38 (3.34) pg/mL by systemic estradiol
      administration for 6 weeks, which also led to further mean (SD) decreases in tear
      film BUT from 5.28 (0.81) to 3.65 (0.55) seconds (P < 0.01) and in SIT result
      from 2.19 (1.01) to 1.47 (0.85) mm (P < 0.05), as well as a higher mean (SD)
      corneal fluorescein staining score from 7.39 (1.34) to 9.89 (1.27) (P < 0.05).
      However, the mean (SD) testosterone level was increased to 3.53 (0.67) ng/mL by
      systemic testosterone administration for 6 weeks. As a result, the mean (SD) tear
      film BUT increased from 5.08 (0.40) to 6.03 (1.48) seconds (P < 0.05), and the
      mean (SD) SIT result increased from 2.38 (1.20) to 3.66 (1.90) mm (P < 0.05). The
      mean (SD) corneal fluorescein staining score declined from 7.45 (0.73) to 4.56
      (1.21) (P < 0.05). In the nontreated OVX group, the mean (SD) MMP-2 mRNA (0.66
      [0.10]) and protein (0.55 [0.13]) expression in lacrimal glands was significantly
      increased compared with that in the sham-operated group (0.50 [0.09] and 0.40
      [0.07], respectively) (P < 0.05). Systemic estradiol administration further
      increased the mean (SD) MMP-2 mRNA (0.83 [0.10]) and protein (0.69 [0.12])
      expression (P < 0.05), while systemic testosterone administration decreased the
      mean (SD) MMP-2 mRNA (0.12 [0.04]) and protein (0.27 [0.07]) expression (P <
      0.01). Topical ophthalmic administration of two sex hormones had no effect on the
      mean (SD) MMP-2 mRNA (0.59 [0.12] for estradiol and 0.57 [0.14] for testosterone)
      or protein (0.49 [0.11] for estradiol and 0.46 [0.13] for testosterone)
      expression (P > 0.05). CONCLUSIONS: Ovariectomy-induced ocular surface impairment
      may be associated with androgen deficiency. A pathogenetic role for estrogen in
      dry eye may involve upregulation of MMP-2 expression, while androgen suppresses
      MMP-2 expression.

PMID- 24334445
TI  - Endothelial cell microRNA expression in human late-onset Fuchs' dystrophy.
AB  - PURPOSE: MicroRNAs (miRNAs) are a class of endogenous noncoding RNA and post
      transcriptionally modulate gene expression during development and disease. Our
      study investigated the differential miRNA expression in human Fuchs' endothelial
      corneal dystrophy (FECD) compared with normal endothelium to identify miRNA
      sequences that are involved in the pathogenesis of FECD. METHODS: Comparative
      miRNA expression profiles of endothelial samples obtained from FECD patients
      during lamellar corneal transplant surgery and from normal donor globes were
      generated using OpenArray plate technology. Differential expression of individual
      miRNAs was validated in the original and in independent samples using stem-loop
      RT qPCR assays. Expression of miRNA target genes was assessed using qPCR and
      tissue microarray (TMA) immunolabeling. RESULTS: Our results demonstrate
      downregulation of 87 miRNAs in FECD compared with normal endothelium (>3-fold
      change; P < 0.01). Correspondingly, DICER1, (encoding an endoribonuclease
      critical to miRNA biogenesis) showed a moderate but significant decrease in FECD
      samples (P < 0.05). Significant repression of three miR-29 family members (miR
      29a-3p, miR-29b-2-5p, and miR-29c-5p) was paralleled by upregulation of their
      extracellular matrix associated mRNA targets collagen I and collagen IV. Tissue
      microarray immunolabeling showed histologically verifiable subendothelial
      collagen I and collagen IV deposition and increased endothelial laminin protein
      expression in FECD samples. CONCLUSIONS: The present study provides the first
      miRNA profile in FECD and normal endothelial cells and demonstrates widespread
      miRNA downregulation in FECD. Decreased endothelial expression of miR-29 family
      members may be associated with increased subendothelial extracellular matrix
      accumulation in FECD.

PMID- 24334446
TI  - Fcgamma receptor upregulation is associated with immune complex inflammation in
      the mouse retina and early age-related macular degeneration.
AB  - PURPOSE: Several lines of evidence suggest the involvement of antibodies and
      immune complex inflammation in AMD, a blinding disease with a strong inflammatory
      component. To examine this further, we developed a novel experimental mouse model
      of retinal inflammation and evaluated whether inflammation associated with immune
      complex formation was present in eyes of AMD donors. METHODS: A localized immune
      complex-mediated reaction was induced in the retina of wild-type (WT), Fc
      receptor gamma chain-deficient (gamma(-/-)), and C1q-deficient (C1q(-/-)) mice,
      and donor eyes were obtained after death from donors with early or wet AMD and
      from healthy control subjects. The presence of immune complexes, Fcgamma
      receptors (FcgammaRs), and markers of macrophage/microglia activation was
      investigated by immunohistochemistry. RESULTS: In WT and C1q(-/-) mice, immune
      complex deposition in the retina led to a robust inflammatory response with
      activation of microglia, recruitment of myeloid cells, and increased expression
      of FcgammaRI through FcgammaRIV and major histocompatibility complex class II.
      This response was not observed in gamma(-/-) mice lacking activating FcgammaRs.
      We found that early AMD was associated with deposition of IgG, C1q, and membrane
      attack complex in the choriocapillaris and with increased numbers of CD45+ cells
      expressing FcgammaRIIa and FcgammaRIIb. Furthermore, FcgammaRIIa and FcgammaRIIb
      were observed in eyes of donors with wet AMD. CONCLUSIONS: Our studies suggest
      that immune complexes may contribute to AMD pathogenesis through interaction of
      IgG with FcgammaRs and might inform about possible adverse effects associated
      with therapeutic antibodies.

PMID- 24334447
TI  - Long-term retinal cone survival and delayed alteration of the cone mosaic in a
      transgenic mouse model of stargardt-like dystrophy (STGD3).
AB  - PURPOSE: To examine the pattern of cone degeneration in the retina of a
      transgenic mouse model of Stargartd-like dystrophy (STGD3). METHODS:
      Investigations were performed on ELOVL4/TG1-2 transgenic (TG) mice and wild-type
      (WT) littermates from 1 to 24 months of age. Phenotypes were assessed by fundus
      imaging, fatty acid analysis, and electroretinogram (ERG) recording. Cone
      degeneration pattern was determined on retina whole mounts using
      immunohistochemistry and Voronoi domain analyses. RESULTS: Consistent with low
      transgene expression, photoreceptors degenerate very slowly. At 1 month,
      anatomical structure and fatty acid composition of the TG retina is comparable
      with WT. Rod loss appears at 2 months, exhibiting a central to peripheral
      gradient, and fundus defects are observed at 3 months. In contrast, cone
      morphology, distribution and function are still normal at 12 months. Cone loss
      becomes apparent at 15 months when the outer nuclear layer is reduced to 3 to 4
      photoreceptor rows. This process starts at the center of the retina and affects
      cone subtypes similarly. Very few cones remain at 24 months, after all rods have
      disappeared (18 months). Quantitative studies focusing on cones expressing M
      opsin show a net increase in Voronoi domains and a significant decrease in
      regularity indexes only beyond 15 months. CONCLUSIONS: Photoreceptor degeneration
      in this STGD3 mouse model follows the time course of a slow rod-cone dystrophy.
      The cone mosaic is preserved for almost 1 year after the onset of rod loss. This
      long delay provides an opportunity to examine rod-cone interactions during
      retinal degeneration and to test therapeutic effectiveness at protracting cone
      dysfunction.

PMID- 24334448
TI  - Corneal biomechanical properties and glaucoma-related quantitative traits in the
      EPIC-Norfolk Eye Study.
AB  - PURPOSE: We examined the association of corneal hysteresis (CH) with Heidelberg
      retina tomograph (HRT)- and Glaucoma Detection with Variable Corneal Compensation
      scanning laser polarimeter (GDxVCC)-derived measures in a British population.
      METHODS: The EPIC-Norfolk Eye Study is nested within a multicenter cohort study-
      the European Prospective Investigation of Cancer. Ocular response analyzer (ORA),
      HRT3, and GDxVCC measurements were taken at the research clinic. Three ORA
      measurements were taken per eye, and the single best value used. Participants
      meeting predefined criteria were referred for a second examination, including
      Goldmann applanation tonometry (GAT) and central corneal thickness (CCT)
      measurement. Generalized estimating equation models were used to examine the
      associations of CH with HRT and GDxVCC parameters, adjusted for disc area. The
      GDxVCC analyses were adjusted further for typical scan score to handle atypical
      retardation. RESULTS: There were complete research clinic data from 5134
      participants. Corneal hysteresis was associated positively with HRT rim area (P <
      0.001), and GDxVCC retinal nerve fiber layer (RNFL) average thickness (P = 0.006)
      and modulation (P = 0.003), and associated negatively with HRT linear cup-to-disc
      ratio (LCDR, P < 0.001), after adjustment for Goldmann-correlated IOP and other
      possible confounders. In the 602 participants undergoing the second examination,
      CH was associated negatively with LCDR (P = 0.008) after adjustment for GAT, CCT,
      and other possible confounders. CONCLUSIONS: Lower CH was associated with HRT and
      GDxVCC parameters in a direction that is seen in glaucoma and with ageing.
      Further research is required to establish if this is a causal relationship, or
      due to residual confounding by age, IOP, or CCT.

PMID- 24334449
TI  - Systemic upregulation of PDGF-B in patients with neovascular AMD.
AB  - PURPOSE: To determine the plasma levels of platelet-derived growth factor-B (PDGF
      B), VEGF, and TNF-alpha in patients with neovascular AMD and in patients with
      diabetic macular edema (DME). METHODS: Thirty patients with neovascular AMD, 30
      patients with DME, and 12 healthy controls were included in this prospective
      study. The concentrations of PDGF-B, VEGF, and TNF-alpha were measured by ELISA.
      RESULTS: The PDGF-B concentration in the plasma of controls was (median [25th
      75th percentile]) 263.5 (162.0-513.3) pg/mL and in patients with DME 219.0 (122.8
      604.8) pg/mL. In patients with neovascular AMD, PDGF-B levels were significantly
      higher with a median plasma concentration of 783.5 (289.3-1183.5) pg/mL (P =
      0.003). The VEGF concentrations in patients with DME 33.0 (21.8-73.0) pg/mL and
      in patients with neovascular AMD 55.0 (37.0-116.3) pg/mL showed no significant
      differences (P = 0.159). A positive correlation of PDGF-B and VEGF plasma levels
      was found in patients with neovascular AMD and in patients with DME (r = 0.683, P
      < 0.001, and r = 0.612, P < 0.001, respectively). No significant differences of
      systemic TNF-alpha levels could be found between the three study groups.
      CONCLUSIONS: Patients with neovascular AMD have significantly higher plasma PDGF
      B levels compared with patients with DME and healthy controls. Our study data
      indicate that PDGF-B may be involved in the pathogenesis of neovascular AMD.
      (https://eudract.ema.europa.eu number, EudraCT 2010-024654-11)

PMID- 24334451
TI  - Topographic characteristics of optic disc hemorrhage in primary open-angle
      glaucoma.
AB  - PURPOSE: To investigate the topographic characteristics of optic disc hemorrhage
      (DH) and the factors associated with DH area in POAG. METHODS: We enrolled 128
      POAG eyes (with DH) of 128 patients consecutively. Digital red-free retinal nerve
      fiber layer (RNFL) photographs and digital color stereo disc photographs of the
      enrolled eyes were reviewed, and the DH locations were measured. The DH area was
      calculated based on RNFL deviation map/RNFL photographs overlay image. RESULTS:
      Disc hemorrhages were most common in the inferotemporal inferior sector (58.0%)
      and the disc rim (40.6%) in terms of octant and proximal location, respectively.
      In a multivariate analysis, a larger DH area was associated with older age (P <
      0.01), use of acetylsalicylic acid (P = 0.03), lower cup-to-disc ratio (P <
      0.01), and lower baseline IOP (P = 0.01). In normal-baseline IOP-POAG eyes (n =
      88), the overall DH area and length of maximum radial extent of DH were larger
      than in high-baseline IOP-POAG eyes (n = 40) (P = 0.04 and 0.03, respectively).
      CONCLUSIONS: In POAG eyes, DH was larger in area and longer in length in cases of
      normal-baseline IOP than in cases of high-baseline IOP. This suggests the
      possibility that previous studies' findings of higher DH prevalence and incidence
      in normal-baseline IOP-POAG eyes were partially affected by these topographic
      characteristics, which make DH more easily detectable.

PMID- 24334450
TI  - Eye-specific IOP-induced displacements and deformations of human lamina cribrosa.
AB  - PURPOSE: To measure high-resolution eye-specific displacements and deformations
      induced within the human LC microstructure by an acute increase in IOP. METHODS:
      Six eyes from donors aged 23 to 82 were scanned using second harmonic-generated
      (SHG) imaging at various levels of IOP from 10 to 50 mm Hg. An image registration
      technique was developed, tested, and used to find the deformation mapping between
      maximum intensity projection images acquired at low and elevated IOP. The
      mappings were analyzed to determine the magnitude and distribution of the IOP
      induced displacements and deformations and contralateral similarity. RESULTS:
      Images of the LC were obtained and the registration technique was successful. IOP
      increases produced substantial, and potentially biologically significant, levels
      of in-plane LC stretch and compression (reaching 10%-25% medians and 20%-30% 75th
      percentiles). Deformations were sometimes highly focal and concentrated in
      regions as small as a few pores. Regions of largest displacement, stretch,
      compression, and shear did not colocalize. Displacements and strains were not
      normally distributed. Contralateral eyes did not always have more similar
      responses to IOP than unrelated eyes. Under elevated IOP, some LC regions were
      under bi-axial stretch, others under bi-axial compression. CONCLUSIONS: We
      obtained eye-specific measurements of the complex effects of IOP on the LC with
      unprecedented resolution in uncut and unfixed human eyes. Our technique was
      robust to electronic and speckle noise. Elevated IOP produced substantial in
      plane LC stretch and compression. Further research will explore the effects of
      IOP on the LC in a three-dimensional framework.

PMID- 24334452
TI  - Risk factors for unfavorable pregnancy outcome in women with adverse childhood
      experiences.
AB  - AIMS: To explore the association between childhood sexual abuse (CSA), physical
      abuse, as well as other adverse childhood experiences (ACE), and different
      obstetrical risk factors/behaviors. METHODS: In this cohort study, obstetrical
      risk factors and perinatal outcome in 85 women exposed to CSA were compared to
      170 matched unexposed women. CSA, physical abuse, and ACE were explored by face
      to-face interviews and by questionnaire. Data on perinatal outcome were extracted
      from medical charts. Fisher's exact, chi2-test, and multiple logistic regression
      were used for statistical analysis. RESULTS: During pregnancy women with CSA
      experiences were significantly more often smoking (31.7%/9.4%; P<0.0001), had
      partners abusing drugs (10.6%/1.2%; P<0.0005), experienced physical (16.5%/0;
      P<0.0001), sexual (12.9%/0; P<0.0001), and emotional abuse (44.7%/1.7%;
      P<0.0001), reported depression (24.7%/1.8%; P<0.0001), and suicidal ideation
      (10.6%/0; P<0.0001) than women without CSA experiences. Differences in risk
      factors were more often correlated with physical than with sexual abuse during
      childhood. The probability for premature delivery was associated with CSA,
      physical abuse and ACE as well as with several of the risk factors investigated.
      CONCLUSION: Women with CSA, physical, and ACE present with a variety of abuse
      associated obstetrical risk factors and an increased risk for premature delivery.
      Therefore, all types of abusive and other ACE should be considered in prenatal
      care.

PMID- 24334453
TI  - Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity.
AB  - Acute myelogenous leukemia (AML) subtypes that result from oncogenic activation
      of homeobox (HOX) transcription factors are associated with poor prognosis. The
      HOXA9 transcription activator and growth factor independent 1 (GFI1)
      transcriptional repressor compete for occupancy at DNA-binding sites for the
      regulation of common target genes. We exploited this HOXA9 versus GFI1 antagonism
      to identify the genes encoding microRNA-21 and microRNA-196b as transcriptional
      targets of HOX-based leukemia oncoproteins. Therapeutic inhibition of microRNA-21
      and microRNA-196b inhibited in vitro leukemic colony forming activity and
      depleted in vivo leukemia-initiating cell activity of HOX-based leukemias, which
      led to leukemia-free survival in a murine AML model and delayed disease onset in
      xenograft models. These data establish microRNA as functional effectors of
      endogenous HOXA9 and HOX-based leukemia oncoproteins, provide a concise in vivo
      platform to test RNA therapeutics, and suggest therapeutic value for microRNA
      antagonists in AML. 

PMID- 24334454
TI  - Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo
      pathway suppression.
AB  - Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle
      characterized by expression of the paired box 3-forkhead box protein O1 (PAX3
      FOXO1) fusion oncogene. Despite its discovery nearly two decades ago, the
      mechanisms by which PAX3-FOXO1 drives tumor development are not well
      characterized. Previously, we reported that PAX3-FOXO1 supports aRMS initiation
      by enabling bypass of cellular senescence checkpoints. We have now found that
      this bypass occurs in part through PAX3-FOXO1-mediated upregulation of RASSF4, a
      Ras-association domain family (RASSF) member. RASSF4 expression was upregulated
      in PAX3-FOXO1-positive aRMS cell lines and tumors. Enhanced RASSF4 expression
      promoted cell cycle progression, senescence evasion, and tumorigenesis through
      inhibition of the Hippo pathway tumor suppressor MST1. We also found that the
      downstream Hippo pathway target Yes-associated protein 1 (YAP), which is
      ordinarily restrained by Hippo signaling, was upregulated in RMS tumors. These
      data suggest that Hippo pathway dysfunction promotes RMS. This work provides
      evidence for Hippo pathway suppression in aRMS and demonstrates a progrowth role
      for RASSF4. Additionally, we identify a mechanism used by PAX3-FOXO1 to inhibit
      MST1 signaling and promote tumorigenesis in aRMS. 

PMID- 24334455
TI  - Nervous glucose sensing regulates postnatal beta cell proliferation and glucose
      homeostasis.
AB  - How glucose sensing by the nervous system impacts the regulation of beta cell
      mass and function during postnatal development and throughout adulthood is
      incompletely understood. Here, we studied mice with inactivation of glucose
      transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed
      normal energy homeostasis but developed late-onset glucose intolerance due to
      reduced insulin secretion, which was precipitated by high-fat diet feeding. The
      beta cell mass of adult NG2KO mice was reduced compared with that of WT mice due
      to lower beta cell proliferation rates in NG2KO mice during the early postnatal
      period. The difference in proliferation between NG2KO and control islets was
      abolished by ganglionic blockade or by weaning the mice on a carbohydrate-free
      diet. In adult NG2KO mice, first-phase insulin secretion was lost, and these
      glucose-intolerant mice developed impaired glucagon secretion when fed a high-fat
      diet. Electrophysiological recordings showed reduced parasympathetic nerve
      activity in the basal state and no stimulation by glucose. Furthermore,
      sympathetic activity was also insensitive to glucose. Collectively, our data show
      that GLUT2-dependent control of parasympathetic activity defines a nervous
      system/endocrine pancreas axis that is critical for beta cell mass establishment
      in the postnatal period and for long-term maintenance of beta cell function. 

PMID- 24334456
TI  - p16INK4a reporter mice reveal age-promoting effects of environmental toxicants.
AB  - While murine-based systems to identify cancer-promoting agents (carcinogens) are
      established, models to identify compounds that promote aging (gerontogens) have
      not been described. For this purpose, we exploited the transcription of p16INK4a,
      which rises dynamically with aging and correlates with age-associated disease.
      Activation of p16INK4a was visualized in vivo using a murine strain that harbors
      a knockin of the luciferase gene into the Cdkn2a locus (p16LUC mice). We exposed
      p16LUC mice to candidate gerontogens, including arsenic, high-fat diet, UV light,
      and cigarette smoke and serially imaged animals to monitor senescence induction.
      We show that exposure to a high-fat diet did not accelerate p16INK4a expression,
      whereas arsenic modestly augmented, and cigarette smoke and UV light potently
      augmented, activation of p16INK4a-mediated senescence. This work provides a
      toxicological platform to study mammalian aging and suggests agents that directly
      damage DNA promote molecular aging. 

PMID- 24334457
TI  - Carbon monoxide-based therapy ameliorates acute pancreatitis via TLR4 inhibition.
AB  - The protective role of hemeoxygenase-1 (HO-1) in various inflammatory conditions
      is mediated in part by its products, carbon monoxide (CO) and biliverdin. Here we
      investigated a therapeutic role for CO and CO-primed cells in acute pancreatitis
      (AP). In a mouse model of AP, treatment with CO-releasing molecule-2 (CORM-2)
      decreased mortality, pancreatic damage, and lung injury. CORM-2 decreased
      systemic inflammatory cytokines, suppressed systemic and pancreatic macrophage
      TNF-alpha secretion, and inhibited macrophage TLR4 receptor complex expression.
      In both human and mouse cells, CORM-2 inhibited endogenous and exogenous ligand
      dependent TLR4 activation, which indicates that CORM-2 could be therapeutic for
      both early and late stages of AP, which involve sterile- and endotoxin-mediated
      inflammation, respectively. Mice engrafted with TLR4-deficient hematopoietic
      cells were protected against caerulein-induced AP. In the absence of leukocyte
      TLR4 expression, CORM-2 did not confer additional protection, which indicates
      that CORM-2-dependent effects are mediated via suppression of macrophage TLR4
      activation. We determined that CO was directly responsible for the protective
      effects of CORM-2 in AP, as inactive forms of CORM-2 were ineffective.
      Importantly, adoptive transfer of CORM-2-primed cells reduced AP. Such a
      therapeutic approach would translate the beneficial effects of CO-based
      therapies, avoiding CO- or CO-RM-mediated toxicities in AP and a wide range of
      diseases. 

PMID- 24334458
TI  - Pancreatic cancer-associated retinoblastoma 1 dysfunction enables TGF-beta to
      promote proliferation.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is often associated with overexpression
      of TGF-beta. Given its tumor suppressor functions, it is unclear whether TGF-beta
      is a valid therapeutic target for PDAC. Here, we found that proliferating
      pancreatic cancer cells (PCCs) from human PDAC patients and multiple murine
      models of PDAC (mPDAC) often exhibit abundant levels of phosphorylated
      retinoblastoma 1 (RB) and Smad2. TGF-beta1 treatment enhanced proliferation of
      PCCs isolated from KrasG12D-driven mPDAC that lacked RB (KRC cells). This
      mitogenic effect was abrogated by pharmacological inhibition of type I TGF-beta
      receptor kinase, combined inhibition of MEK/Src or MEK/PI3K, and restoration of
      RB expression. TGF-beta1 promoted epithelial-to-mesenchymal transition (EMT),
      invasion, Smad2/3 phosphorylation, Src activation, Wnt reporter activity, and
      Smad-dependent upregulation of Wnt7b in KRC cells. Importantly, TGF-beta1-induced
      mitogenesis was markedly attenuated by inhibition of Wnt secretion. In an in vivo
      syngeneic orthotopic model, inhibition of TGF-beta signaling suppressed KRC cell
      proliferation, tumor growth, stroma formation, EMT, metastasis, ascites
      formation, and Wnt7b expression, and markedly prolonged survival. Together, these
      data indicate that RB dysfunction converts TGF-beta to a mitogen that activates
      known oncogenic signaling pathways and upregulates Wnt7b, which synergize to
      promote PCC invasion, survival, and mitogenesis. Furthermore, this study suggests
      that concomitantly targeting TGF-beta and Wnt7b signaling in PDAC may disrupt
      these aberrant pathways, which warrants further evaluation in preclinical models.

PMID- 24334462
TI  - Controllable light-induced conic structures in silicon nanowire arrays by metal
      assisted chemical etching.
AB  - Silicon nanowires (SiNWs) have long been considered a promising material due to
      their extraordinary electrical and optical properties. As a simple, highly
      efficient fabrication method for SiNWs, metal-assisted chemical etching (MACE)
      has been intensively studied over recent years. However, effective control by
      modulation of simple parameters is still a challenging topic and some key
      questions still remain in the mechanistic processes. In this work, a novel method
      to manipulate SiNWs with a light-modulated MACE process has been systematically
      investigated. Conic structures consisting of inclined and clustered SiNWs can be
      generated and effectively modified by the incident light while new patterns such
      as 'bamboo shoot' arrays can also be formed under certain conditions. More
      importantly, detailed study has revealed a new top-down 'diverting etching' model
      of the conic structures in this process, different from the previously proposed
      'bending' model. As a consequence of this mechanism, preferential lateral mass
      transport of silver particles occurs. Evidence suggests a relationship of this
      phenomenon to the inhomogeneous distribution of the light-induced electron-hole
      pairs beneath the etching front. Study on the morphological change and related
      mechanism will hopefully open new routes to understand and modulate the formation
      of SiNWs and other nanostructures. 

PMID- 24334461
TI  - Quantitative characterization of hepatocellular carcinoma and metastatic liver
      tumor by CT perfusion.
AB  - PURPOSE: To evaluate the diagnostic value of computed tomography perfusion (CTP)
      in the distinction of hepatocellular carcinomas (HCCs) from metastatic liver
      tumors. MATERIALS AND METHODS: CTP data from 90 liver tumors (HCC 38, metastasis
      52) in 31 patients (16 men and 15 women; mean age 60.3 years) were studied. CTP
      was performed on a 16/64 multidetector-row CT scanner using a 30-s duration cine
      acquisition after rapid bolus injection (5-7 ml/s) of 50-70 ml of iodinated
      contrast medium. The CTP data were analyzed using a deconvolution model.
      Metastatic tumors were grouped into hypovascular (n = 36) and hypervascular (n =
      16) tumors. RESULTS AND CONCLUSION: The hypovascular metastases showed a
      significantly lower blood flow (BF) and blood volume (BV), and higher mean
      transit time (MTT) than HCC (all P < 0.0001). BF, BV, and MTT of HCCs were
      substantially lower than those of hypervascular metastases (P = 0.02, P < 0.0001,
      P = 0.03, respectively). A receiver-operating characteristic analysis showed that
      BV was a useful marker to distinguish HCCs from hypervascular metastases.

PMID- 24334459
TI  - Complement factor H-related hybrid protein deregulates complement in dense
      deposit disease.
AB  - The renal disorder C3 glomerulopathy with dense deposit disease (C3G-DDD) pattern
      results from complement dysfunction and primarily affects children and young
      adults. There is no effective treatment, and patients often progress to end-stage
      renal failure. A small fraction of C3G-DDD cases linked to factor H or C3 gene
      mutations as well as autoantibodies have been reported. Here, we examined an
      index family with 2 patients with C3G-DDD and identified a chromosomal deletion
      in the complement factor H-related (CFHR) gene cluster. This deletion resulted in
      expression of a hybrid CFHR2-CFHR5 plasma protein. The recombinant hybrid protein
      stabilized the C3 convertase and reduced factor H-mediated convertase decay. One
      patient was refractory to plasma replacement and exchange therapy, as evidenced
      by the hybrid protein quickly returning to pretreatment plasma levels.
      Subsequently, complement inhibitors were tested on serum from the patient for
      their ability to block activity of CFHR2-CFHR5. Soluble CR1 restored defective C3
      convertase regulation; however, neither eculizumab nor tagged compstatin had any
      effect. Our findings provide insight into the importance of CFHR proteins for C3
      convertase regulation and identify a genetic variation in the CFHR gene cluster
      that promotes C3G-DDD. Monitoring copy number and sequence variations in the CFHR
      gene cluster in C3G-DDD and kidney patients with C3G-DDD variations will help
      guide treatment strategies. 

PMID- 24334460
TI  - Lysosomal beta-glucuronidase regulates Lyme and rheumatoid arthritis severity.
AB  - Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most
      prevalent arthropod-borne illness in the United States and remains a clinical and
      social challenge. The spectrum of disease severity among infected patients
      suggests that host genetics contribute to pathogenic outcomes, particularly in
      patients who develop arthritis. Using a forward genetics approach, we identified
      the lysosomal enzyme beta-glucuronidase (GUSB), a member of a large family of
      coregulated lysosomal enzymes, as a key regulator of Lyme-associated arthritis
      severity. Severely arthritic C3H mice possessed a naturally occurring hypomorphic
      allele, Gusbh. C57BL/6 mice congenic for the C3H Gusb allele were prone to
      increased Lyme-associated arthritis severity. Radiation chimera experiments
      revealed that resident joint cells drive arthritis susceptibility. C3H mice
      expressing WT Gusb as a transgene were protected from severe Lyme arthritis.
      Importantly, the Gusbh allele also exacerbated disease in a serum transfer model
      of rheumatoid arthritis. A known GUSB function is the prevention of lysosomal
      accumulation of glycosaminoglycans (GAGs). Development of Lyme and rheumatoid
      arthritis in Gusbh-expressing mice was associated with heightened accumulation of
      GAGs in joint tissue. We propose that GUSB modulates arthritis pathogenesis by
      preventing accumulation of proinflammatory GAGs within inflamed joint tissue, a
      trait that may be shared by other lysosomal exoglycosidases. 

PMID- 24334463
TI  - Combined deficiency of proteins C and S: ischaemic stroke in young individuals.
AB  - In adults of any age, the majority of strokes are ischaemic (caused by a blockage
      in the blood supply to the brain). Stroke in young individuals poses a major
      health problem. The WHO defines stroke as an event caused by the interruption of
      the blood supply to the brain, usually because of rupture of a blood vessel or
      blockage by a clot. This hampers the supply of oxygen and nutrients, causing
      damage to the brain tissue. Globally, stroke is the third commonest cause of
      mortality and the fourth leading cause of disease burden. Ischaemic stroke is the
      most common cerebrovascular disease, most often due to atherothrombotic diseases
      and uncommonly by disorders of hypercoagulation. Disorders of coagulation leading
      to thrombotic disorders are approximately 1% of all ischaemic strokes and 4-8% of
      strokes in young individuals. Similarly, combined deficiency of proteins C and S
      can lead to hypercoagulable state and rarely presents as a cerebrovascular
      accident. We describe here a case of a 25-year-old man who presented with right
      middle cerebral artery territory infarct due to protein C and S deficiency. 

PMID- 24334464
TI  - Cat scratch disease and lymph node tuberculosis in a colon patient with cancer.
AB  - A 71-year-old man operated for a sigmoid tumour remained in the surveillance
      after adjuvant chemotherapy. After 3 years, a left axillary lymph node was
      visible on CT scan. The biopsy revealed a necrotising and abscessed granulomatous
      lymphadenitis, suggestive of cat scratch disease. The patient confirmed having
      been scratched by a cat and the serology for Bartonella henselae was IgM+/IgG-.
      Direct and culture examinations for tuberculosis were negative. The patient was
      treated for cat scratch disease. One year later, the CT scan showed increased
      left axillary lymph nodes and a left pleural effusion. Direct and cultural
      examinations to exclude tuberculosis were again negative. Interferon-gamma
      release assay testing for tuberculosis was undetermined and then positive. Lymph
      node and pleural tuberculosis were diagnosed and treated with a good radiological
      response. This article has provides evidence of the importance of continued
      search for the right diagnosis and that two diagnoses can happen in the same
      patient. 

PMID- 24334465
TI  - Pipeline endovascular reconstruction of traumatic dissecting aneurysms of the
      intracranial internal carotid artery.
AB  - A 22-year-old woman was involved in a motor vehicle collision resulting in
      multiple facial fractures and extensive internal carotid artery (ICA) injury
      including a right carotid-cavernous fistula, complex dissection flap and
      dissecting aneurysms. Endovascular coil embolization was initially performed to
      treat the cavernous carotid fistula and then again on two separate occasions to
      treat expanding dissecting aneurysms. Parent vessel reconstruction of the right
      ICA was subsequently performed with the Pipeline embolization device, resulting
      in complete anatomical restoration of this vessel. 

PMID- 24334466
TI  - Posterior fossa dural arteriovenous fistula presenting clinically as a carotid
      cavernous fistula treated by a direct access cavernous sinus approach.
AB  - Dural arteriovenous fistulas (dAVFs) represent approximately 10-15% of all
      cerebral vascular malformations. Although dAVFs can occur anywhere in the brain,
      they occur most frequently in the cavernous and transverse-sigmoid sinuses.
      Posterior fossa dAVFs presenting clinically as carotid-cavernous fistulae (CCF)
      are rarely encountered in clinical practice. We discuss and illustrate an unusual
      case of a left posterior fossa dAVF that presented clinically with chemosis and
      early visual impairment, similar to that of CCF. This was subsequently treated by
      a direct access cavernous sinus approach. We describe the technique used to
      access the cavernous sinus directly in cases where conventional transvenous and
      transarterial routes have been exhausted. 

PMID- 24334467
TI  - Tubercular duodenal, jejunal and ileocecal stricture in a patient.
AB  - Gastrointestinal tuberculosis is a major health problem in the developing
      countries. Duodenal involvement is uncommon and can mimic superior mesenteric
      artery syndrome. Our case presented as proximal intestinal obstruction had
      tubercular stricture in the third part of the duodenum, proximal jejunum and
      ileocecal region, an uncommon and difficult intraoperative situation. 

PMID- 24334468
TI  - Isolated major aortopulmonary collateral artery in an infant presenting with
      recurrent lower respiratory tract infection.

PMID- 24334469
TI  - Non-puerperal uterine inversion caused by malignant mixed mullerian sarcoma.
AB  - Non puerperal uterine inversions resulting from mixed mullerian uterine sarcoma
      are rare. We present a case of a postmenopausal woman with a large mixed
      mullerian tumour presenting as a huge abdominopelvic mass. It required a
      challenging surgical procedure to remove the tumour which is also described along
      with the review of literature. 

PMID- 24334470
TI  - Dasatinib-induced haemorrhagic colitis in chronic myeloid leukaemia (CML) in
      blast crisis.
AB  - We report a rare case of haemorrhagic colitis attributed to dasatinib therapy in
      a 47-year-old African-American woman who was diagnosed with extramedullary T
      lymphoblastic transformation of chronic myeloid leukaemia. The patient received
      intensive chemotherapy and dasatinib 100 mg/day. After achieving complete
      cytogenetic and major molecular response after 9 months of therapy, she developed
      bloody diarrhoea and pancytopenia. Colonoscopy showed inflammation of the
      descending colon and histopathology revealed patchy increase in intraepithelial
      lymphocytes. Dasatinib was stopped with prompt resolution of diarrhoea. The
      current literature suggests that there is an association in a subset of patients
      on dasatinib between clonal T-cell lymphocytosis in the peripheral blood and
      developing colitis and pleural effusions. These patients had a good response to
      dasatinib as did our patient. Our patient illustrates a unique disease
      presentation along with a rare drug adverse event. 

PMID- 24334471
TI  - Zenker's diverticulum complicating achalasia: a 'cup-and-spill' oesophagus.
AB  - A 72-year-old woman presented with long-standing gastro-oesophageal reflux,
      regurgitation of swallowed food and worsening cervical dysphagia. Fluoroscopic
      barium oesophagography revealed a posterolateral pharyngeal pouch (Zenker's
      diverticulum (ZD)) complicating a 'cup and spill' oesophageal deformity with a
      smoothly tapered segment at the gastro-oesophageal junction. CT and high
      resolution manometry confirmed that the underlying abnormality was a massively
      dilated oesophagus with aperistalsis and pan-oesophageal pressurisation,
      consistent with a diagnosis of oesophageal achalasia (type II). She underwent
      endoscopic stapled diverticulotomy, with good symptomatic relief. We discuss the
      aetiology of ZD, its management and the association here with oesophageal
      achalasia. 

PMID- 24334472
TI  - Oral submucous fibrosis: a premalignant condition in a 14-year-old Indian girl.
AB  - A 14-year-old Indian girl presented with difficulty in mouth opening and burning
      sensation while eating. On examination, blanching of the oral mucosa with diffuse
      white pigmented lesion of size 3.5 to 2 cm along with melanotic pigmentation was
      seen on the left buccal mucosa posteriorly. The patient was diagnosed with oral
      submucous fibrosis. A comprehensive treatment plan was made based on conservative
      management that included motivation and intense counselling of the patient and
      her parents so that she quits the habit of chewing areca nut and tobacco, along
      with systemic treatment of vitamin B complex supplements, antioxidants,
      multivitamins and oral physiotherapy. We present this case to highlight the
      difficulties faced by the clinical practitioners in providing treatment because
      of the taboos and myths associated with surgical treatment modality in rural
      population as well as to emphasise the menace of increasing consumption and
      availability of tobacco and areca nut to children. 

PMID- 24334473
TI  - Sarcoidosis: clinical mimicry of pulmonary embolism.
AB  - Sarcoidosis can manifest with clinical signs suggestive of pulmonary embolism
      (PE). A 36-year-old male patient presented with a 2-day history of left-sided
      pleuritic chest pain and dyspnoea. He was hypoxicand tachypnoeic, and initial
      blood tests showed a positive plasma D-dimer. Subsequent arterial blood gas
      showed respiratory alkalosis with type 1 respiratory failure. He was suspected to
      have a PE, and CT pulmonary angiogram (CTPA) was urgently arranged. This latter
      investigation did not show any impairment in pulmonary arterial blood flow but
      revealed bilateral hilar and mediastinal lymphadenopathy suggesting sarcoidosis.
      Serum calcium and ACE were also elevated. The patient was treated conservatively
      and discharged after 2 days with out-patient endobronchial ultrasound and clinic
      follow-up arranged. 

PMID- 24334474
TI  - Symptomatic ureteric triplex in a child.
AB  - We describe a case of a triplex system in a 4-year-old girl that was associated
      with a ureterocele and vesicoureteric reflux and causing symptomatic culture
      proven urinary tract infections. Undetected on preoperative ultrasound imaging
      and micturating cystourethrogram, this was discovered at the time of a planned
      left heminephrectomy. The redundant system having been removed the patient is now
      asymptomatic. 

PMID- 24334475
TI  - Announcing a new section: Global health and cancer.

PMID- 24334476
TI  - The global challenge of reducing breast cancer mortality.

PMID- 24334477
TI  - Screen-and-treat approach to cervical cancer prevention using visual inspection
      with acetic acid and cryotherapy: experiences, perceptions, and beliefs from
      demonstration projects in Peru, Uganda, and Vietnam.
AB  - Cervical cancer is preventable but continues to cause the deaths of more than
      270,000 women worldwide each year, most of them in developing countries where
      programs to detect and treat precancerous lesions are not affordable or
      available. Studies have demonstrated that screening by visual inspection of the
      cervix using acetic acid (VIA) is a simple, affordable, and sensitive test that
      can identify precancerous changes of the cervix so that treatment such as
      cryotherapy can be provided. Government partners implemented screening and
      treatment using VIA and cryotherapy at demonstration sites in Peru, Uganda, and
      Vietnam. Evaluations were conducted in the three countries to explore the
      barriers and facilitating factors for the use of services and for incorporation
      of screen-and-treat programs using VIA and cryotherapy into routine services.
      Results showed that use of VIA and cryotherapy in these settings is a feasible
      approach to providing cervical cancer prevention services. Activities that can
      help ensure successful programs include mobilizing and educating communities,
      organizing services to meet women's schedules and needs, and strengthening
      systems to track clients for follow-up. Sustainability also depends on having an
      adequate number of trained providers and reducing staff turnover. Although some
      challenges were found across all sites, others varied from country to country,
      suggesting that careful assessments before beginning new secondary prevention
      programs will optimize the probability of success. 

PMID- 24334478
TI  - Advancing cervical cancer prevention in India: implementation science priorities.
AB  - Cervical cancer is the leading cause of cancer mortality in India, accounting for
      17% of all cancer deaths among women aged 30 to 69 years. At current incidence
      rates, the annual burden of new cases in India is projected to increase to
      225,000 by 2025, but there are few large-scale, organized cervical cancer
      prevention programs in the country. We conducted a review of the cervical cancer
      prevention research literature and programmatic experiences in India to summarize
      the current state of knowledge and practices and recommend research priorities to
      address the gap in services. We found that research and programs in India have
      demonstrated the feasibility and acceptability of cervical cancer prevention
      efforts and that screening strategies requiring minimal additional human
      resources and laboratory infrastructure can reduce morbidity and mortality.
      However, additional evidence generated through implementation science research is
      needed to ensure that cervical cancer prevention efforts have the desired impact
      and are cost-effective. Specifically, implementation science research is needed
      to understand individual- and community-level barriers to screening and
      diagnostic and treatment services; to improve health care worker performance; to
      strengthen links among screening, diagnosis, and treatment; and to determine
      optimal program design, outcomes, and costs. With a quarter of the global burden
      of cervical cancer in India, there is no better time than now to translate
      research findings to practice. Implementation science can help ensure that
      investments in cervical cancer prevention and control result in the greatest
      impact. 

PMID- 24334479
TI  - Breast cancer in young women in Latin America: an unmet, growing burden.
AB  - BACKGROUND: Breast cancer (BC) is the leading cause of malignancy-related deaths
      among women aged <= 45 years. There are unexplored and uncertain issues for BC in
      this particular group in Latin America. The aim of this study is to evaluate BC
      incidence and mortality among young women and related clinicopathological and
      survivorship aspects in this region. MATERIALS AND METHODS: Data were obtained
      from Globocan 2008 and the International Agency for Research on Cancer's Cancer
      Incidence in Five Continents series plus databases. We requested collaboration
      from the 12 different national cancer institutes in Latin America through SLACOM,
      the Latin American and Caribbean Society of Medical Oncology, and conducted a
      systematic literature review to obtain local data regarding the prevalence of BC
      among young women and their characteristics, outcomes, and survivorship-related
      issues. RESULTS: BC incidence and mortality proportions for Latin American women
      aged <44 years were higher when compared with those of developed countries (20%
      vs. 12% and 14% vs. 7%, respectively). We found only a few Latin American series
      addressing this topic, and prevalence varied between 8% and 14%. Stage II and III
      disease, high histological grade, and triple-negative and HER2 BC were features
      frequently observed among young Latin American BC patients. CONCLUSION: The
      rising incidence and mortality of BC in young Latin American women is a call to
      action in the region. It is necessary to monitor the epidemiological and clinical
      data through reliable cancer registries and to consider the implementation of
      protocols for education of patients and health professionals. This unmet, growing
      burden must be considered as a top priority of the national programs in the fight
      against BC, and models of specialized units should be implemented for this
      particular group of patients to provide better care for this emergent challenge.

PMID- 24334480
TI  - Thermodiffusion in binary liquids: the role of irreversibility.
AB  - We study thermal diffusion in binary mixtures in the framework of non-equilibrium
      thermodynamics. Our formal result displays the role of partial enthalpies hi and
      Onsager's generalized mobilities Ai. The ratio A1/A2 provides a measure for the
      irreversible character of thermal diffusion. Comparison with experimental data on
      benzene, cyclohexane, toluene and n-alkanes shows that irreversibility is
      essential for thermal diffusion, and in particular for the isotope effect. 

PMID- 24334481
TI  - Effects of coil orientation on the electric field induced by TMS over the hand
      motor area.
AB  - Responses elicited by transcranial magnetic stimulation (TMS) over the hand motor
      area depend on the position and orientation of the stimulating coil. In this
      work, we computationally investigate the induced electric field for multiple coil
      orientations and locations in order to determine which parts of the brain are
      affected and how the sensitivity of motor cortical activation depends on the
      direction of the electric field. The finite element method is used for
      calculating the electric field induced by TMS in two individual anatomical models
      of the head and brain. The orientation of the coil affects both the strength and
      depth of penetration of the electric field, and the field strongly depends on the
      direction of the sulcus, where the target neurons are located. The coil position
      that gives the strongest electric field in the target cortical region may deviate
      from the closest scalp location by a distance on the order of 1 cm. Together with
      previous experimental data, the results support the hypothesis that the cortex is
      most sensitive to fields oriented perpendicular to the cortical layers, while it
      is relatively insensitive to fields parallel to them. This has important
      implications for targeting of TMS. To determine the most effective coil position
      and orientation, it is essential to consider both biological (the direction of
      the targeted axons) and physical factors (the strength and direction of the
      electric field). 

PMID- 24334482
TI  - A direct arylation-derived DPP-based small molecule for solution-processed
      organic solar cells.
AB  - A diketo-pyrrolo-pyrrole (DPP) oligomer containing three DPP cores (Ph4Th4(DPP)3)
      was synthesized via direct arylation of C-H bonds (DACH). Ph4Th4(DPP)3 has good
      solubility in many organic solvents, and shows a broad absorption band from the
      visible to near-infrared region as well as a field-effect hole mobility as high
      as 0.006 cm(2) V(-1) s(-1). Solution-processed bulk heterojunction organic solar
      cells based on blends of Ph4Th4(DPP)3 as electron donor and fullerene derivative
      as electron acceptor were fabricated. An optimized power conversion efficiency of
      3.76% with a high open-circuit voltage of 0.85 V was achieved after finely tuning
      the morphology by changing the blend ratio and by adding additives. These results
      indicate that DACH is an effective way to produce pi-conjugated oligomers for
      organic solar cells.

PMID- 24334483
TI  - Whole-body vibration training improves balance, muscle strength and glycosylated
      hemoglobin in elderly patients with diabetic neuropathy.
AB  - Elderly patients with diabetes and peripheral neuropathy are more likely to
      experience falls. However, the information available on how such falls can be
      prevented is scarce. We investigated the effects of whole-body vibration (WBV)
      combined with a balance exercise program on balance, muscle strength, and
      glycosylated hemoglobin (HbA1c) in elderly patients with diabetic peripheral
      neuropathy. Fifty-five elderly patients with diabetic neuropathy were randomly
      assigned to WBV with balance exercise group, balance exercise (BE) group, and
      control group. The WBV and BE groups performed the balance exercise program for
      60 min per day, 2 times per week, for 6 weeks. Further, the WBV group performed
      WBV training (up to 3 * 3 min, 3 times per week, for 6 weeks). The control group
      did not participate in any training. The main outcome measures were assessed at
      baseline and after 6 weeks of training; namely, we assessed the postural sway and
      one leg stance (OLS) for static balance; Berg balance scale (BBS), timed up-and
      go (TUG) test, and functional reach test (FRT) for dynamic balance; five-times
      sit-to-stand (FTSTS) test for muscle strength; and HbA1c for predicting the
      progression of diabetes. Significant improvements were noted in the static
      balance, dynamic balance, muscle strength, and HbA1c in the WBV group, compared
      to the BE and control groups (P < 0.05). Thus, in combination with the balance
      exercise program, the short-term WBV therapy is beneficial in improving balance,
      muscle strength and HbA1c, in elderly patients with diabetic neuropathy who are
      at high risk for suffering falls. 

PMID- 24334484
TI  - Selection of an aptamer against mouse GP2 by SELEX.
AB  - Microfold (M) cells are intestinal epithelial cells specialized for sampling and
      transport of luminal antigens to gut-associated lymphoid tissue for initiation of
      both mucosal and systemic immune responses. Therefore, M-cell targeted
      vaccination has the potential to be a better immunization strategy. Glycoprotein
      2 (GP2), an antigen uptake receptor for FimH(+) bacteria on M cells, can be a
      good target for this purpose. Aptamers are oligonucleotides that bind to a
      variety of target molecules with high specificity and affinity. Together with its
      low toxic feature, aptamers serves as a tool of molecular-targeted delivery. In
      this study, we used Systematic Evolution of Ligands by EXponential enrichment
      (SELEX) to isolate aptamers specific to murine GP2 (mGP2). After ten rounds of
      SELEX, eleven different aptamer sequences were selected. Among them, the most
      frequently appeared sequence (~60%) were aptamer NO. 1 (Apt1), and the second
      most (~7%) were aptamer NO. 5 (Apt5). In vitro binding experiment confirmed that
      only Apt1 and Apt5 specifically bound to mGP2 among eleven aptamers initially
      selected. Apt1 showed the strongest affinity with mGP2, with the Kd value of
      110+/-2.6 nM evaluated by BIACORE. Binding assays with mutants of Apt1 suggest
      that, in addition to the loop structure, the nucleotide sequence, AAAUA, in the
      loop is important for binding to mGP2. Furthermore, this aptamer was able to bind
      to mGP2 expressed on the cell surface. These results suggest that this mGP2
      specific aptamer could serve as a valuable tool for testing M-cell-targeted
      vaccine delivery in the murine model system. 

PMID- 24334485
TI  - Paleogenomics, hominin interbreeding and language evolution.

PMID- 24334486
TI  - Language and hybrids: too many answers for too few questions.

PMID- 24334487
TI  - Was there language outside Homo sapiens? A cognitive perspective.

PMID- 24334488
TI  - Archaic human genomes and language evolution.

PMID- 24334489
TI  - What serves as evidence for the presence (or absence)of Pleistocene language?

PMID- 24334490
TI  - Social learning and origin of the language faculty by means of natural selection.

PMID- 24334491
TI  - A minor role for genetics in language evolution.

PMID- 24334492
TI  - The origins of language: in search for the specificity of large-brained hominin
      languages.

PMID- 24334493
TI  - Hominin interbreeding and language evolution: fine-tuning the details.

PMID- 24334495
TI  - Hydrazine-promoted sequential cation exchange: a novel synthesis method for doped
      ternary semiconductor nanocrystals with tunable emission.
AB  - Using ZnSe nanocrystals (NCs) as starting material, Ag-doped or Cu-doped ZnCdSe
      ternary NCs were prepared by hydrazine-promoted sequential cation exchange in
      aqueous media. The composition of the NCs can be flexibly controlled by varying
      the amount of intermediate Ag or Cu cation addition, thus changing the emission
      of the ternary NCs while preserving the NC size. According to Vegard's law, the
      as-prepared ternary NCs possess an alloyed structure. In addition, the ternary
      NCs obtained have a high quantum yield, strong stability and a broad optical
      tuning range. 

PMID- 24334496
TI  - First-principles study of the lattice dynamical properties of strontium
      ruthenate.
AB  - By means of first-principles calculations, various properties of SrRuO3 are
      investigated, focusing on its lattice dynamical properties. Despite having a
      Goldschmidt tolerance factor very close to 1, the phonon dispersion curves of the
      high-temperature cubic phase of SrRuO3 show strong antiferrodistortive
      instabilities. The energetics of metastable phases with different tilt patterns
      are discussed, concluding that the coupling of oxygen rotation modes with anti
      polar Sr motion plays a key role in stabilizing the Pnma phase with respect to
      alternative rotation patterns. Our systematic analysis confirms previous
      expectations and contributes to rationalizing better why many ABO3 perovskites,
      including metallic compounds, exhibit an orthorhombic ground state. The zone
      center phonon modes of the Pnma phase have been computed, from which we propose
      partial reassignment of available experimental data. The full dispersion curves
      have also been obtained, constituting benchmark results for the interpretation of
      future measurements and providing access to thermodynamical properties. 

PMID- 24334494
TI  - Preoperative easily misdiagnosed telangiectatic osteosarcoma: clinical-radiologic
      pathologic correlations.
AB  - PURPOSE: To describe the clinical, imaging, and pathologic characteristics and
      diagnostic methods of telangiectatic osteosarcoma (TOS) for improving the
      diagnostic level. MATERIALS AND METHODS: The authors retrospectively reviewed
      patient demographics, serum alkaline phosphatase (AKP) levels, preoperative
      biopsy pathologic reports, pathologic materials, imaging findings, and treatment
      outcomes from 26 patients with TOS. Patient images from radiography (26 cases)
      and magnetic resonance (MR) imaging (22 cases) were evaluated by 3 authors in
      consensus for intrinsic characteristics. There were 15 male and 11 female
      patients in the study, with an age of 9-32 years (mean age 15.9 years). RESULTS:
      Eighteen of 26 patients died of lung metastases within 5 years of follow-up. The
      distal femur was affected more commonly (14 cases, 53.8%). Regarding serum AKP,
      normal (8 cases) or mildly elevated (18 cases) levels were found before
      preoperative chemotherapy. Radiographs showed geographic bone lysis without
      sclerotic margin (26 cases), cortical destruction (26 cases), periosteal new bone
      formation (24 cases), soft-tissue mass (23 cases), and matrix mineralization (4
      cases). The aggressive radiographic features of TOS simulated the appearance of
      conventional high-grade intramedullary osteosarcoma, though different from
      aneurysmal bone cyst. MR images demonstrated multiple big (16 cases) or small (6
      cases) cystic spaces, fluid-fluid levels (14 cases), soft-tissue mass (22 cases),
      and thick peripheral and septal enhancement (22 cases). Nine of 26 cases were
      misdiagnosed as aneurysmal bone cysts by preoperative core-needle biopsy, owing
      to the absence of viable high-grade sarcomatous cells in the small tissue
      samples. CONCLUSION: The aggressive growth pattern with occasional matrix
      mineralization, and multiple big or small fluid-filled cavities with thick
      peripheral, septal, and nodular tissue surrounding the fluid-filled cavities are
      characteristic imaging features of TOS, and these features are helpful in making
      the correct preoperative diagnosis of TOS.

PMID- 24334497
TI  - Effects of downregulation of S100A8 protein expression on cell cycle and
      apoptosis of fibroblasts derived from hypertrophic scars.
AB  - BACKGROUND: Uncontrolled growth and lack of apoptosis in fibroblasts derived from
      a hypertrophic scar play an important role in pathology. OBJECTIVE: The authors
      explore the contribution of S100A8 overexpression to the phenotype of cells and
      discuss how the downregulation of S100A8 could inhibit the growth and induce
      apoptosis of fibroblasts derived from hypertrophic scars. METHODS: Fibroblasts
      were harvested from hypertrophic scar tissue in 8 patients treated with small
      interfering RNA against S100A8 in an in vitro culture. The effects of silencing
      S100A8 were analyzed by Western blot. Cellular proliferation and apoptosis were
      detected by flow cytometry. RESULTS: Fibroblasts treated with small interfering
      RNA targeting S100A8 showed a significant decrease in S100A8 protein 48 hours
      after treatment. They also proliferated significantly slower and showed more
      apoptosis than control fibroblasts. CONCLUSIONS: Inhibition of S100A8 resulted in
      significant growth reduction and apoptosis acceleration in fibroblasts derived
      from hypertrophic scars. Manipulation of S100A8 protein expression by gene
      silencing may represent something new in the treatment of hypertrophic scarring.

PMID- 24334498
TI  - Desire for body contouring surgery after bariatric surgery: do body mass index
      and weight loss matter?
AB  - BACKGROUND: There is disparity between the number of postbariatric surgery
      subjects who desire body contouring and those who receive it due to lack of
      resources or insurance criteria. OBJECTIVES: The authors evaluate the desire for
      body contouring after bariatric surgery and its relationship with demographic
      patient characteristics. METHODS: Three hundred sixty patients who had undergone
      bariatric surgery procedures >1 year previously completed a questionnaire
      designed by the surgical team to analyze each patient's desire for body
      contouring by area (face, upper arm, upper back, chin/neck, chest/breast,
      waist/abdomen, lower back, rear/buttock), scored from 0 to 3 (do not want, want
      somewhat, want, want a great deal). Data were compared with patient
      characteristics, postoperative body mass index (BMI), amount of weight loss, and
      BMI difference (DeltaBMI). RESULTS: Most patients desired body contouring
      surgery, with high or very high desire for waist/abdomen (62.2%), upper arm
      (37.6%), chest/breast (28.3%), and rear/buttock (35.6%) contouring. Many patients
      (36.4%) cited "very high" expectations for how body contouring might change their
      appearance. Patients >50 years old and >3 years postsurgery had a significantly
      lower desire. Patients with a DeltaBMI >10 and with a weight loss >20 kg showed a
      significantly stronger overall desire for body contouring compared with other
      groups. CONCLUSIONS: Most patients desire body contouring surgery after bariatric
      surgery, and our multivariate analysis showed a significant positive association
      between female sex, younger age, amount of weight loss, and DeltaBMI with desire
      for body contouring.

PMID- 24334499
TI  - Complications following reduction mammaplasty: a review of 3538 cases from the
      2005-2010 NSQIP data sets.
AB  - BACKGROUND: Reduction mammaplasty is an established and effective technique to
      treat symptomatic macromastia. Variable rates of complications have been
      reported, and there is a continued need for better outcome assessment studies.
      OBJECTIVE: The authors investigate predictors of postoperative complications
      following reduction mammaplasty using the National Surgery Quality Improvement
      Program (NSQIP) data sets. METHODS: The 2005-2010 American College of Surgeons
      NSQIP databases were reviewed to identify primary encounters for reduction
      mammaplasty using Current Procedural Terminology code 19318. Two complication
      types were recorded: major complications (deep infection and return to operating
      room) and any complication (all surgical complications). Preoperative patient
      factors and comorbidities, as well as intraoperative variables, were assessed. A
      multivariate regression analysis was used to identify independent predictors of
      complications. RESULTS: A total of 3538 patients were identified with an average
      age of 43 years and body mass index of 31.6 kg/m(2). Most patients underwent
      outpatient surgery (80.5%) with an average operative time of 180 minutes. The
      incidence of overall surgical complications was 5.1%. The following factors were
      independently associated with any surgical complications: morbid obesity (odds
      ratio [OR], 2.1; P < .001), active smoking (OR, 1.7; P < .001), history of
      dyspnea (OR, 2.0; P < .001), and resident participation (OR, 1.8; P = .01). The
      incidence of major surgical complications was 2.1%. Factors associated with major
      complications included active smoking (OR, 2.7; P < .001), dyspnea (OR, 2.6; P <
      .001), resident participation (OR, 2.1; P < .001), and inpatient surgery (OR,
      1.8; P = .01). CONCLUSIONS: This study demonstrates overall incidence of
      complications in 1 in 20 patients and a 1 in 50 incidence of a major surgical
      complication. Noteworthy findings include the identification of morbid obesity as
      a significant predictor of overall morbidity and active smoking as a strong
      predictor of major surgical morbidity. These data can assist surgeons in
      preoperative counseling and enhance perioperative decision making.

PMID- 24334500
TI  - Supratip-plasty: a completely cartilaginous tip complex to maintain nasal tip
      width.
AB  - BACKGROUND: Following primary rhinoplasty, the nasal tip may become wider on
      front view, possibly due to splaying of the lateral crura. OBJECTIVES: The
      authors describe a technique, the "supratip-plasty," to create an all
      cartilaginous supratip that resists splaying and postoperative broadening of the
      nasal tip complex. METHODS: Thirteen consecutive primary rhinoplasty patients (10
      women; 3 men) with broad nasal tips received a supratip-plasty (which preserved
      the cephalic part of the lateral crus, reducing it in size and securing it to the
      dorsal septum, resulting in a completely cartilaginous tip framework) and were
      followed for 11 to 17 months. Since the frontal tip width (TW) is relative to the
      frontal nasal base width (NBW), the TW/NBW ratio was contrasted to that of 19
      unoperated aesthetically pleasing nasal tips. RESULTS: Of the 13 cases, all but 1
      were considered to have a good result. The preoperative mean TW/NBW ratio was
      0.68. The postoperative mean was 0.53, compared with 0.48 in the unoperated
      aesthetic tip group. No tip revisions were necessary; however, 2 patients did
      require revisionary surgery for nontip problems. CONCLUSIONS: Preserving a
      cephalic island of lateral crus, trimming it to fit the new supratip contour
      following suture tip-plasty, and securing it to the septum provides a completely
      cartilaginous nasal tip framework that tends not to widen postoperatively.

PMID- 24334501
TI  - The inverted-T mammaplasty: a modified winch suture to reduce horizontal scar
      length.
AB  - Mammaplasty performed with an inverted-T skin resection pattern is a useful
      technique to treat moderately or severely ptotic breasts. This method of skin
      resection is conducted via 3 incisional components: periareolar, vertical, and
      horizontal. In this report, the authors describe a simple modified winch suture
      that can be inserted with the inverted-T technique to reduce the length of the
      horizontal incision. 

PMID- 24334502
TI  - Impaired survival of autologous fat grafts by diabetes mellitus in an animal
      model: a pilot study.
AB  - BACKGROUND: Many surgeons are reluctant to perform fat grafting in patients with
      diabetes because soft-tissue healing is impaired, but no previous study has
      reported data-driven outcomes of fat grafting in subjects with diabetes.
      OBJECTIVE: The authors investigate whether diabetes affected survival and
      complication rates of autologous fat grafting (AFG) in Sprague-Dawley (SD) and
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: In total, 16 male SD and
      16 male OLETF rats were prepared for AFG. Fat tissue was harvested from the
      inguinal fat pad and cut into 1-g (800-1250 mg) sections. Each rat received fat
      in a subcutaneous pocket in the paraspinal area. The grafted fat tissue was
      measured by ultrasonography at 30, 60, and 90 days after implantation and
      evaluated by histological analyses. RESULTS: Ultrasonographic analysis indicated
      that compared with the SD group, the AFG survival rate was lower in OLETF rats
      (40.52% vs 53.38%), and the failure rate was higher in OLETF rats (31.25% vs
      6.25%). The histological analysis indicated that compared with the OLETF group,
      adipocytes were more dense (3.18 vs 2.33; P = .025), cyst formation occurred less
      frequently (3.00 vs 3.61; P = .030), and more capillaries were formed (2.31/field
      vs 1.61/field; P = .001) in the SD rat group. CONCLUSIONS: Diabetes causes marked
      deterioration in the survival and quality of AFG in the diabetic rat model.

PMID- 24334503
TI  - The importance of sports medicine for the Sochi Games.

PMID- 24334504
TI  - Head injuries among FIS World Cup alpine and freestyle skiers and snowboarders: a
      7-year cohort study.
AB  - BACKGROUND: Traumatic brain injury is the leading cause of death for skiers and
      snowboarders. Fatal head injuries have also occurred at the International Ski
      Federation (FIS) World Cup (WC) level. We therefore wanted to describe the risk
      of head injuries across disciplines and sex among WC skiers and snowboarders.
      METHOD: We conducted retrospective interviews with FIS WC athletes at the end of
      seven consecutive seasons (2006-2013) to register injuries sustained during the
      competitive season. Head injuries were classified as 'head/face' injuries and did
      not include neck or cervical spine injuries. To calculate the exposure, we
      extracted data from the official FIS website for all WC competitions for each of
      the athletes interviewed. RESULTS: A total of 2080 injuries were reported during
      seven WC seasons. Of these, 245 (11.8%) were head/face injuries. Of the 245
      head/face injuries reported, nervous system injuries/concussions were the most
      common (81.6%) and 58 of these were severe (23.7%). The injury incidence per 1000
      competition runs was higher in freestyle (1.8, 95% CI 1.2 to 2.4) than in alpine
      skiing (0.9, 95% CI 0.6 to 1.2; risk ratio (RR) 2.05, 95% CI 1.25 to 3.46) and
      snowboard (1.0, 95% CI 0.6 to 1.3; RR 1.85, 95% CI 1.15 to 2.99). Women had a
      higher injury incidence (5.8, 95% CI 4.8 to 6.9) versus men (3.9, 95% CI 3.2 to
      4.6; RR 1.48, 95% CI 1.15 to 1.90) throughout the season (per 100 athletes).
      CONCLUSIONS: The majority of head/face injuries were nervous system
      injuries/concussions and one in four injuries was severe. Freestyle skiers had
      the highest overall head injury incidence. Across all disciplines, the injury
      incidence was higher in women than in men.

PMID- 24334505
TI  - The epidemiology of professional ice hockey injuries: a prospective report of six
      NHL seasons.
AB  - BACKGROUND: There is a paucity of literature examining injury and illness rates
      in men's professional ice hockey. This study aimed to determine injury and
      illness rates in the NHL over six seasons, and identify predictors of injury
      related time loss in this population. METHODS: This study involved an inclusive
      cohort of hockey players from all NHL teams competing in the 2006-2007 through
      2011-2012 seasons. A standardised electronic injury surveillance system was used
      to report injury and illness events. The primary outcome was regular season and
      postseason time-loss injury/illness. The secondary outcome was man-games lost
      from the competition. RESULTS: On the basis of the estimated athlete exposures
      (AEs), the overall regular season incidence density was 15.6 injuries/1000 AEs
      and 0.7 illnesses/1000 AEs. Based on recorded time on ice, the injury rates were
      roughly threefold higher at 49.4 injuries/1000 player game-hours and 2.4
      illnesses/1000 player game-hours. There was a reduction in injury rates over the
      6-year period, with the greatest reduction between the 2007-2008 and 2008-2009
      seasons. Multivariate predictors of time loss greater than 10 days were being a
      goalie (OR=1.68, 95% CI 1.18 to 2.38), being injured in a road game (OR=1.43, 95%
      CI 1.25 to 1.63) and the mechanism of injury being a body check (OR=2.21, 95% CI
      1.86 to 2.62). CONCLUSIONS: There was an overall reduction in the time-loss
      injury and illness rates over six seasons. Being a goaltender, being injured on
      the road and being injured by a body check were the risk factors for time loss
      greater than five 'man games'.

PMID- 24334506
TI  - The role of sports physiotherapy at the London 2012 Olympic Games.
AB  - BACKGROUND: There is a lack of information on the utilisation of physiotherapy
      services at the Olympic Games. AIM: To better understand the athlete and non
      athlete requirements of the physiotherapy services at the Olympic Village
      Polyclinic during the London 2012 Olympic Games. METHODS: From 16 July to 14
      August 2012, physiotherapy encounters for athletes and non-athletes (National
      Olympic Committee (NOC) team officials, coaches, team managers, workforce,
      Olympic family, technical officials and press) were recorded on the ATOS
      electronic medical records system at the polyclinic in the main Athletes' Village
      in Stratford. RESULTS: Of the 1778 encounters, 1219 (69%) were administered to
      athletes and 559 (31%) to non-athletes. The anatomical areas most frequently
      recorded at the first visits for athletes were knee (15.4%), lumbar spine/lower
      back (15.2%) and upper leg (12.6%) and that for non-athletes were lumbar
      spine/lower back (19.8%), knee (15.8%) and neck/cervical spine. Muscle (33.3%)
      and joint injuries (24.8%) were the most common diagnoses in athletes and non
      athletes (24.4% and 30.1%). The five most frequently used treatment modalities
      were therapeutic soft tissue techniques (23.3%), mobilisation techniques (21.8%),
      taping (8.9%), cryotherapy (6.9%) and exercise prescription (6.4%). The most
      common cause of athletes' injuries was overuse (43.6%). CONCLUSIONS: This study
      of the London 2012 Olympic Games workload highlights the physiotherapy needs of
      athletes as well as non-athletes and identifies the high numbers of pre-existing
      and overuse injuries in this setting, providing an insight into the reasons why
      the athletes seek physiotherapy support during the Olympic Games.

PMID- 24334507
TI  - L-shell x-ray fluorescence computed tomography (XFCT) imaging of Cisplatin.
AB  - X-ray fluorescence computed tomography (XFCT) imaging has been focused on the
      detection of K-shell x-rays. The potential utility of L-shell x-ray XFCT is,
      however, not well studied. Here we report the first Monte Carlo (MC) simulation
      of preclinical L-shell XFCT imaging of Cisplatin. We built MC models for both L-
      and K-shell XFCT with different excitation energies (15 and 30 keV for L-shell
      and 80 keV for K-shell XFCT). Two small-animal sized imaging phantoms of 2 and 4
      cm diameter containing a series of objects of 0.6 to 2.7 mm in diameter at 0.7 to
      16 mm depths with 10 to 250 ug mL(-1) concentrations of Pt are used in the study.
      Transmitted and scattered x-rays were collected with photon-integrating
      transmission detector and photon-counting detector arc, respectively. Collected
      data were rearranged into XFCT and transmission CT sinograms for image
      reconstruction. XFCT images were reconstructed with filtered back-projection and
      with iterative maximum-likelihood expectation maximization without and with
      attenuation correction. While K-shell XFCT was capable of providing an accurate
      measurement of Cisplatin concentration, its sensitivity was 4.4 and 3.0 times
      lower than that of L-shell XFCT with 15 keV excitation beam for the 2 cm and 4 cm
      diameter phantom, respectively. With the inclusion of excitation and fluorescence
      beam attenuation correction, we found that L-shell XFCT was capable of providing
      fairly accurate information of Cisplatin concentration distribution. With a dose
      of 29 and 58 mGy, clinically relevant Cisplatin Pt concentrations of 10 ug mg(-1)
      could be imaged with L-shell XFCT inside a 2 cm and 4 cm diameter object,
      respectively. 

PMID- 24334508
TI  - Using well-defined Ag nanocubes as substrates to quantify the spatial resolution
      and penetration depth of surface-enhanced Raman scattering imaging.
AB  - The multiplexing capability and high sensitivity of surface-enhanced Raman
      scattering (SERS) make this new imaging modality particularly attractive for
      rapid diagnosis. With 100 nm Ag nanocubes serving as the substrate, this work
      quantitatively evaluated, for the first time, some of the fundamental parameters
      of SERS imaging such as blur, spatial resolution and penetration depth. Our
      results imply that SERS is a high-resolution imaging technique with a blur value
      of 0.5 MUm that is lower than many traditional modalities such as mammography.
      The spatial resolution was measured to be 1.1 MUm, suggesting that SERS images
      could be collected effectively by adjusting the imaging step size to the same
      length scale, or no more than 2 MUm. The major drawback of SERS imaging is its
      penetration depth, which is limited by the scattering and absorption of tissues.
      We demonstrated that enhancement of signal caused by aggregation of multiple
      nanoparticles could help overcome this potential road-block to in vivo imaging.

PMID- 24334509
TI  - Resource use efficiency of closed plant production system with artificial light:
      concept, estimation and application to plant factory.
AB  - Extensive research has recently been conducted on plant factory with artificial
      light, which is one type of closed plant production system (CPPS) consisting of a
      thermally insulated and airtight structure, a multi-tier system with lighting
      devices, air conditioners and fans, a CO2 supply unit, a nutrient solution supply
      unit, and an environment control unit. One of the research outcomes is the
      concept of resource use efficiency (RUE) of CPPS.This paper reviews the
      characteristics of the CPPS compared with those of the greenhouse, mainly from
      the viewpoint of RUE, which is defined as the ratio of the amount of the resource
      fixed or held in plants to the amount of the resource supplied to the CPPS.It is
      shown that the use efficiencies of water, CO2 and light energy are considerably
      higher in the CPPS than those in the greenhouse. On the other hand, there is much
      more room for improving the light and electric energy use efficiencies of CPPS.
      Challenging issues for CPPS and RUE are also discussed.

PMID- 24334511
TI  - Assembling cell context-specific gene sets: a case in cardiomyopathy.
AB  - An increasing amount of evidence suggests that canonical pathways and standard
      molecular signature databases are incomplete and inadequate to model the complex
      behavior of cell physiology and pathology. Yet, many Gene Set Analysis (GSA)
      studies still rely on these databases to identify disease biomarkers and
      molecular mechanisms within a specific cell context. While tremendous effort has
      been invested in developing GSA tools, there is limited number of studies
      focusing on de novo assembly of context-specific gene sets as opposed to simply
      applying GSA using the standard gene set database. In this paper, we propose a
      pipeline to derive the entire collection of Cell context-Specific Gene Sets
      (CSGS) from a molecular interaction network, based on the hypothesis that
      molecular events linked to a specific phenotypic response should cluster within a
      subnet of interacting genes. Gene sets are assigned using both physical
      properties of the network and functional annotations of the neighboring nodes.
      The identified gene sets could provide a precise starting point such that the
      downstream GSA will cover all functional pathways in this particular cell context
      and, at the same time, avoid the noise and excessive multiple-hypothesis testing
      due to inclusion of irrelevant gene sets from the standard database. We applied
      the pipeline in the context of cardiomyopathy and demonstrated its superiority
      over MSigDB gene set collection in terms of: (i) reproducibility and robustness
      in GSA, (ii) effectiveness in uncovering molecular mechanisms associated with
      cardiomyopathy, and (iii) the performance in distinguishing diseased vs. normal
      states. 

PMID- 24334510
TI  - Life course health care and preemptive approach to non-communicable diseases.
AB  - Non-communicable diseases (NCDs), such as diabetes mellitus and coronary heart
      disease, are chronic, non-infectious diseases of long duration. NCDs are
      increasingly widespread worldwide and are becoming a serious health and economic
      burden. NCDs arise from complex interactions between the genetic make-up of an
      individual and environmental factors. Several epidemiological studies have
      revealed that the perinatal environment influences health later in life, and have
      proposed the concept of developmental programming or developmental origin of
      health and disease (DOHaD). These studies suggest the importance of life course
      health care from fetal life, early childhood, adulthood, and through to old age.
      Recent progress in genomics, proteomics and diagnostic modalities holds promise
      for identifying high risk groups, predicting latent diseases, and allowing early
      intervention. Preemptive medicine is the ultimate goal of medicine, but to
      achieve it, the full participation of the public and all sectors of society is
      imperative.

PMID- 24334512
TI  - One-to-one spatially matched experiment and atomistic simulations of nanometre
      scale indentation.
AB  - We have carried out nanoindentation studies of gold in which the indenter is
      atomically characterized by field-ion microscopy and the scale of deformation is
      sufficiently small to be directly compared with atomistic simulations. We find
      that many features of the experiment are correctly reproduced by molecular
      dynamics simulations, in some cases only when an atomically rough indenter rather
      than a smooth repulsive-potential indenter is used. Heterogeneous nucleation of
      dislocations is found to take place at surface defect sites. Using input from
      atomistic simulations, a model of indentation based on stochastic transitions
      between continuum elastic-plastic states is developed, which accurately predicts
      the size distributions of plastic 'pop-in' events and their dependence on tip
      geometry. 

PMID- 24334513
TI  - Rat uterine oxytocin receptor and estrogen receptor alpha and beta mRNA levels
      are regulated by estrogen through multiple estrogen receptors.
AB  - Estrogen action is mediated through several types of receptors (ERs), such as
      ERalpha, ERbeta and putative membrane ERs. Oxytocin receptor (OTR) and ER
      expression levels in the rat uterus are regulated by estrogen; however, which
      types of ERs are involved has not been elucidated. This study examined OTR,
      ERalpha and ERbeta levels in ovariectomized rats treated with 17beta-estradiol
      (E2), an ERalpha agonist (PPT), an ERbeta agonist (DPN) or estren (Es). E2 and
      PPT increased OTR mRNA levels and decreased ERalpha and ERbeta mRNA levels 3 and
      6 h posttreatment. DPN decreased ERalpha and ERbeta mRNA levels at 3 and 6 h,
      while OTR mRNA levels increased at 3 h and decreased at 6 h. OTR mRNA levels
      increased 3 h after the Es treatment and then declined until 6 h. ERalpha and
      ERbeta mRNA levels decreased by 3 h and remained low until 6 h posttreatment with
      Es. The ER antagonist ICI182,780 (ICI) suppressed the increases in OTR mRNA
      levels induced 3 h after the Es treatment. However, ICI and tamoxifen (Tam) had
      no significant effect on ERalpha and ERbeta mRNA levels in the Es-treated or
      vehicle-treated group. In intact rats, proestrus-associated increases in OTR mRNA
      levels were antagonized by both ICI and Tam. However, decreases in ERalpha and
      ERbeta mRNA levels were not antagonized by Tam and ICI, respectively. Therefore,
      uterine OTR gene expression is upregulated by estrogen through the classical
      nuclear (or non-nuclear) ERs, ERalpha and ERbeta, while the levels of these ERs
      are downregulated by estrogen through multiple pathways including Es-sensitive
      nonclassical ERs. 

PMID- 24334514
TI  - A short review of basic head and neck interventional procedures in a general
      radiology department.
AB  - Image-guided interventional procedures provide a safe way to diagnose and treat a
      variety of head and neck abnormalities. The procedure time is usually short, and
      most procedures can be performed on an outpatient basis. Knowledge about
      strengths and weaknesses, efficacy, potential complications, and pitfalls of
      these procedures allows the best treatment to be chosen for a particular lesion
      type. This review discusses some of the commonly performed interventional
      radiology procedures in a general radiology department in the management of
      patients with neoplastic diseases in the head and neck region. 

PMID- 24334515
TI  - The postmortem diagnosis of alcoholic ketoacidosis.
AB  - AIMS: The aim of this article is to review the forensic literature covering the
      postmortem investigations that are associated with alcoholic ketoacidosis
      fatalities and report the results of our own analyses. METHODS: Eight cases of
      suspected alcoholic ketoacidosis that had undergone medico-legal investigations
      in our facility from 2011 to 2013 were retrospectively selected. A series of
      laboratory parameters were measured in whole femoral blood, postmortem serum from
      femoral blood, urine and vitreous humor in order to obtain a more general
      overview on the biochemical and metabolic changes that occur during alcoholic
      ketoacidosis. Most of the tested parameters were chosen among those that had been
      described in clinical and forensic literature associated with alcoholic
      ketoacidosis and its complications. RESULTS: Ketone bodies and carbohydrate
      deficient transferrin levels were increased in all cases. Biochemical markers of
      generalized inflammation, volume depletion and undernourishment showed higher
      levels. Adaptive endocrine reactions involving insulin, glucagon, cortisol and
      triiodothyronine were also observed. CONCLUSIONS: Metabolic and biochemical
      disturbances characterizing alcoholic ketoacidosis can be reliably identified in
      the postmortem setting. The correlation of medical history, autopsy findings and
      biochemical results proves therefore decisive in identifying pre-existing
      disorders, excluding alternative causes of death and diagnosing alcoholic
      ketoacidosis as the cause of death.

PMID- 24334516
TI  - The Renyi entanglement entropy of a general quantum dimer model at the RK point:
      a highly efficient algorithm.
AB  - A highly efficient and simple-to-implement Monte Carlo algorithm is proposed for
      the evaluation of the Renyi entanglement entropy (REE) of the quantum dimer model
      (QDM) at the Rokhsar-Kivelson (RK) point. It makes possible the evaluation of REE
      at the RK point to the thermodynamic limit for a general QDM. We apply the
      algorithm to a QDM defined on the triangular and the square lattice in two
      dimensions and the simple and the face centered cubic (fcc) lattice in three
      dimensions. We find the REE on all these lattices follows perfect linear scaling
      in the thermodynamic limit, apart from an even-odd oscillation in the case of the
      square lattice. We also evaluate the topological entanglement entropy (TEE) with
      both a subtraction and an extrapolation procedure. We find the QDMs on both the
      triangular and the fcc lattice exhibit robust Z2 topological order. The expected
      TEE of ln2 is clearly demonstrated in both cases. Our large scale simulation also
      proves the recently proposed extrapolation procedure in cylindrical geometry to
      be a highly reliable way to extract the TEE of a topologically ordered system. 

PMID- 24334517
TI  - An analysis of the gradient-induced electric fields and current densities in
      human models when situated in a hybrid MRI-LINAC system.
AB  - MRI-LINAC is a new image-guided radiotherapy treatment system that combines
      magnetic resonance imaging (MRI) with a linear accelerator (LINAC) in a single
      unit. One drawback is that the pulsing of the split gradient coils of the system
      induces an electric field and currents in the patient which need to be predicted
      and evaluated for patient safety. In this novel numerical study the in situ
      electric fields and associated current densities were evaluated inside tissue
      accurate male and female human voxel models when a number of different split
      geometry gradient coils were operated. The body models were located in the MRI
      LINAC system along the axial and radial directions in three different body
      positions. Each model had a region of interest (ROI) suitable for image-guided
      radiotherapy. The simulation results show that the amplitudes and distributions
      of the field and current density induced by different split x-gradient coils were
      similar with one another in the ROI of the body model, but varied outside of the
      region. The fields and current densities induced by a split classic coil with the
      surface unconnected showed the largest deviation from those given by the
      conventional non-split coils. Another finding indicated that the distributions of
      the peak current densities varied when the body position, orientation or gender
      changed, while the peak electric fields mainly occurred in the skin and fat
      tissues. 

PMID- 24334518
TI  - Incidence and risk factors for drug intolerance and association with incomplete
      treatment for tuberculosis: analysis of national case registers for England,
      Wales and Northern Ireland, 2001-2010.
AB  - Anti-tuberculosis drug regimens are efficacious, but drug intolerance can be
      severe and may impact on treatment completion rates. The Enhanced Tuberculosis
      Surveillance (ETS) system is a case register of all new notifications of
      tuberculosis in England, Wales and Northern Ireland. We conducted a cohort study
      to estimate the incidence of, and risk factors for, drug intolerance reported
      through ETS between 2001 and 2010 and to assess its relationship with treatment
      non-completion. Reports of drug intolerance were found for 868/67,547 (1.28%)
      patients in the cohort, and important risk factors were female sex, older age,
      later case report year and white ethnicity. Drug intolerance was associated with
      an approximate fivefold increased odds of treatment non-completion (p<0.001).
      These results highlight the need for better-tolerated drug regimens and close
      case management of patients at risk of drug intolerance to improve treatment
      completion rates and contribute to more effective disease control.

PMID- 24334519
TI  - Epithelial-mesenchymal transition in lung development and disease: does it exist
      and is it important?
AB  - Epithelial-mesenchymal transition (EMT) is a process when epithelial cells
      gradually transform into mesenchymal-like cells losing their epithelial
      functionality and characteristics. EMT is thought to be involved in the
      pathogenesis of numerous lung diseases ranging from developmental disorders,
      fibrotic tissue remodelling to lung cancer. The most important question--namely
      what is the importance and contribution of EMT in the pathogenesis of several
      chronic lung conditions (asthma, COPD, bronchiolitis obliterans syndrome and lung
      fibrosis)--is currently intensely debated. This review gives a brief insight into
      the mechanism and assessment methods of EMT in various pulmonary diseases and
      summarises the recent literature highlighting the controversial experimental data
      and conclusions.

PMID- 24334520
TI  - The role of perfusion effects in monitoring of chemoradiotherapy of rectal
      carcinoma using diffusion-weighted imaging.
AB  - PURPOSE: The aim of this study was to characterize and understand the therapy
      induced changes in diffusion parameters in rectal carcinoma under
      chemoradiotherapy (CRT). The current literature shows conflicting results in this
      regard. We applied the intravoxel incoherent motion model, which allows for the
      differentiation between diffusion (D) and perfusion (f) effects, to further
      elucidate potential underlying causes for these divergent reports. MATERIALS AND
      METHODS: Eighteen patients with primary rectal carcinoma undergoing preoperative
      CRT were examined before, during, and after neoadjuvant CRT using diffusion
      weighted imaging. Using the intravoxel incoherent motion approach, f and D were
      extracted and compared with postoperative tumor downstaging and volume. RESULTS:
      Initial diffusion-derived parameters were within a narrow range (D1 = 0.94 +/-
      0.12 * 10(-3) mm(2)/s). At follow-up, D rose significantly (D2 = 1.18 +/- 0.13 *
      10(-3) mm(2)/s; P < 0.0001) and continued to increase significantly after CRT (D3
      = 1.24 +/- 0.14 * 10(-3) mm(2)/s; P < 0.0001). The perfusion fraction f did not
      change significantly (f1 = 9.4 +/- 2.0%, f2 = 9.4 +/- 1.7%, f3 = 9.5 +/- 2.7%).
      Mean volume (V) decreased significantly (V1 = 16,992 +/- 13,083 mm(3); V2 =
      12,793 +/- 8317 mm(3), V3 = 9718 +/- 6154 mm(3)). T-downstaging (10:18 patients)
      showed no significant correlation with diffusion-derived parameters. CONCLUSIONS:
      Conflicting results in the literature considering apparent diffusion coefficient
      (ADC) changes in rectal carcinoma under CRT for patients showing T-downstaging
      are unlikely to be due to perfusion effects. Our data support the view that under
      effective therapy, an increase in D/ADC can be observed.

PMID- 24334521
TI  - Unilateral visual loss after spine surgery in the prone position for extradural
      haematoma in a healthy young man.
AB  - This case reports a patient who developed central retinal artery occlusion
      following spinal surgery in the prone position. When placed in this position,
      especially as a result of malposition of the head, the patient may develop
      external compression of the eye which leads to central retinal artery occlusion.
      Therefore, a special precaution must be given for adequate eye protection during
      prolonged prone-positioned spine surgery. 

PMID- 24334522
TI  - Twenty-one bust: a case of chemical transformation of an ingested foreign body.
AB  - The majority of ingested foreign bodies pass of their own accord without causing
      any adverse impact on the patient, while others present a greater management
      dilemma. We present a case of a 36-year-old man admitted to the hospital with a
      10-day history of colicky abdominal pain following voluntary ingestion of
      multiple pairs of vinyl gloves. The plain-film abdominal X-ray confirmed small
      bowel obstruction and gastric bezoar. After failed conservative management he
      opted for endoscopic retrieval. Following exposure to stomach acid the gloves had
      lost their structural integrity becoming hard, sharp and brittle. As a result
      endoscopic removal was abandoned due to the risk of traumatic injury to the
      oesophagus. A midline laparotomy was performed and the gloves were retrieved via
      enterotomy. While many foreign bodies are suitable for endoscopic extraction this
      case demonstrates that the retrieval of vinyl gloves is unlikely to be successful
      due to significant chemical change. 

PMID- 24334523
TI  - Unilateral brain oedema related to focal status epilepticus.
AB  - We present a female patient in her late 30s, with baseline vegetative state
      following prior traumatic brain injury, who presented with prolonged right
      hemispheric status epilepticus. The neuroimaging revealed a striking right-sided
      pancortical oedema with left (crossed) cerebellar diaschisis and dilation of
      right hemispheric arteries. EEG was concordant and showed nearly continuous right
      hemispheric seizure discharges with suppressed background. Infective and vascular
      aetiologies were ruled out. The patient showed clinical and electrographic
      improvement following treatment with antiepileptic drugs. Unilateral cerebral
      oedema is a rare presentation of focal status epilepticus, and should be
      considered as a differential diagnosis in the appropriate clinical scenario. 

PMID- 24334524
TI  - Comment on 'comparative evaluation of two dose optimization methods for image
      guided, highly-conformal, tandem and ovoids cervix brachytherapy planning'.

PMID- 24334525
TI  - Low resilience of the particle-attached bacterial community in response to
      frequent wind-wave disturbance in freshwater mesocosms.
AB  - The most common natural disturbances in shallow lakes are wind-induced waves,
      which cause catastrophic changes in the aquatic fauna of lakes. Recovery from
      these changes is always prolonged. The objective of this study was to understand
      the resilience and recovery of the particle-attached bacterial community
      composition (PABCC) after frequent wind-wave disturbance in a large shallow
      eutrophic lake. To accomplish this, we designed a mesocosm experiment including
      an undisturbed control, and a physically disturbed treatment that stimulated the
      superposition of two different intensities of wind-induced waves in the large
      shallow eutrophic Lake Taihu, China. The PABCC was determined by denaturing
      gradient gel electrophoresis, following by cloning and sequencing of the selected
      samples. We observed that the most marked change of the PABCC occurred in the
      disturbed treatment, in which the concentrations of suspended solids (SS) and the
      water turbidity varied strongly. However, we observed low recovery of the PABCC
      within 4 days post-disturbance when the investigated environmental factors had
      also recovered. Our results indicated that the resistance of the PABCC is low,
      and resilience is also low following frequent disturbance by wind-waves in a
      large shallow eutrophic lake. 

PMID- 24334527
TI  - Device-oriented graphene nanopatterning by mussel-inspired directed block
      copolymer self-assembly.
AB  - Directed self-assembly of a block copolymer is successfully employed to fabricate
      device-oriented graphene nanostructures from CVD grown graphene. We implemented
      mussel-inspired polydopamine adhesive in conjunction with the graphoepitaxy
      principle to tailor graphene nanoribbon arrays and a graphene nanomesh located
      between metal electrodes. Polydopamine adhesive was utilized for facile and
      damage-free surface treatment to complement the low surface energy of pristine
      graphene. Our process minimizes the damage to the ideal graphitic structures and
      electrical properties of graphene during the nanopatterning process. Multi
      channel graphene nanoribbon arrays and a graphene nanomesh were successfully
      fabricated between metal electrodes. 

PMID- 24334526
TI  - Bacterial communities in pigmented biofilms formed on the sandstone bas-relief
      walls of the Bayon Temple, Angkor Thom, Cambodia.
AB  - The Bayon temple in Angkor Thom, Cambodia has shown serious deterioration and is
      subject to the formation of various pigmented biofilms. Because biofilms are
      damaging the bas-reliefs, low reliefs engraved on the surface of sandstone,
      information about the microbial community within them is indispensable to control
      biofilm colonization. PCR-denaturing gradient gel electrophoresis (DGGE) analysis
      of biofilm samples from the pigmented sandstone surfaces showed that the
      bacterial community members in the biofilms differed clearly from those in the
      air and had low sequence similarity to database sequences. Non-destructive
      sampling of biofilm revealed novel bacterial groups of predominantly Rubrobacter
      in salmon pink biofilm, Cyanobacteria in chrome green biofilm, Cyanobacteria and
      Chloroflexi in signal violet biofilm, Chloroflexi in black gray biofilm, and
      Deinococcus-Thermus, Cyanobacteria, and Rubrobacter in blue green biofilm. Serial
      peeling-off of a thick biofilm by layers with adhesive sheets revealed a
      stratified structure: the blue-green biofilm, around which there was serious
      deterioration, was very rich in Cyanobacteria near the surface and Chloroflexi in
      deep layer below. Nitrate ion concentrations were high in the blue-green biofilm.
      The characteristic distribution of bacteria at different biofilm depths provides
      valuable information on not only the biofilm formation process but also the
      sandstone weathering process in the tropics. 

PMID- 24334528
TI  - Observation of strong nano-effect via tuning distributed architecture of graphene
      oxide in poly(propylene carbonate).
AB  - For optimum reinforcement in polymer nanocomposite, a critical challenge is to
      realize the full 'nano-effect' of nanofillers at a high content, which is largely
      hindered by the strong tendency to aggregation of nanofillers. Here, by using a
      solvent-exchange and solution casting approach, we could incorporate a high
      content graphene oxide (GO) into a soft biodegradable CO2-based poly(propylene
      carbonate) (PPC) up to 20 wt% with excellent dispersion. Based on this, the
      distributed architecture of GO could be tuned from a 'GO dotted dispersion' and
      'GO network' to strong 'GO co-continuous structure' with increasing GO content.
      As a result, a very strong 'nano-effect' of GO in the PPC matrix was observed:
      (1) the glass transition temperature of PPC was improved from 25 to 45  degrees 
      C for slightly confined molecular chains, and even to 100  degrees  C for highly
      confined ones; (2) the modified PPC showed drastically enhanced high-temperature
      mechanical properties, comparable to those of traditional polymers such as
      polypropylene (PP) and biopolymer poly(lactic acid) (PLA); and (3) such modified
      PPC exhibited an exciting solvent resistance compared to neat PPC. Our work
      provides an example to improve the high-temperature properties of a polymer via
      formation of filler co-continuous structure.

PMID- 24334529
TI  - Weak itinerant antiferromagnetism in PuIn3 explored using 115In nuclear
      quadrupole resonance.
AB  - The results of (115)In nuclear quadrupole resonance (NQR) measurements on PuIn3
      are reported. Three of the four NQR lines of (115)In expected for nuclear spin I
      = 9/2 are observed. The equal spacing of these lines at 20 K yields the NQR
      frequency of nuQ = 10.45 MHz, and the asymmetry parameter of the electric field
      gradient eta = 0. The NQR line profile and the nuclear spin-lattice relaxation
      rate 1/T1 display an abrupt change at 14 K, which is associated with the onset of
      long-range antiferromagnetic order. The temperature dependences of the staggered
      magnetization MQ(T), extracted from the NQR spectra, and 1/T1 below TN = 14 K are
      well explained by the self-consistent renormalization (SCR) theory for spin
      fluctuations. In addition, the scaling between T1T and MQ(T)/MQ(0) is also
      consistent with the predictions of SCR theory, providing further evidence that
      PuIn3 is a weak itinerant antiferromagnet in which spin fluctuations around the
      antiferromagnetic wavevector play a major role in the system's behavior at finite
      temperatures. 

PMID- 24334530
TI  - Increased firing frequency of spontaneous action potentials in cerebellar
      Purkinje neurons of db/db mice results from altered auto-rhythmicity and
      diminished GABAergic tonic inhibition.
AB  - The hormone leptin, by binding to hypothalamic receptors, suppresses food intake
      and decreases body adiposity. Leptin receptors are also widely expressed in extra
      hypothalamic areas such as hippocampus, amygdala and cerebellum, where leptin
      modulates synaptic transmission. Here we show that a defective leptin receptor
      affects the electrophysiological properties of cerebellar Purkinje neurons (PNs).
      PNs from (db/db) mice recorded in cerebellar slices display a higher firing rate
      of spontaneous action potentials than PNs from wild type (WT) mice. Blockade of
      GABAergic tonic inhibition with bicuculline in WT mice changes the firing pattern
      from continuous, uninterrupted spiking into bursting firing, but bicuculline does
      not produce these alterations in db/db neurons, suggesting that they receive a
      weaker GABAergic inhibitory input. Our results also show that the intrinsic
      firing properties (auto-rhythmicity) of WT and db/db PNs are different. Tonic
      firing of PNs, the only efferent output from the cerebellar cortex, is a
      persistent signal to downstream cerebellar targets. The significance of leptin
      modulation of PNs spontaneous firing is not known. Also, it is not clear if the
      increased excitability of cerebellar PNs in db/db mice results from hyperglycemia
      or from the lack of leptin signaling, since both conditions coexist in the db/db
      strain. 

PMID- 24334531
TI  - A physiological view and structures of mean residence times.
AB  - The author's previous theoretical study described the determination of a
      physiologically realistic structure of a mean residence time of an intravenously
      administered drug (Durisova 2012). This study continues previous work and the aim
      is to determine physiologically realistic structures of mean residence times of a
      drug administered either orally (MRTpo) or intramuscularly (MRTim). The
      determinations are based on the following assumption: a cardiopulmonary, portal,
      portal-venous, hepatic-portal subsystem, and a subsystem that mathematically
      represents non-eliminating tissues can be considered to be most important in
      terms of their impact on MRTpo and MRTim. If drug fate and disposition is a
      linear process, the used method allows developing mathematical models without any
      prior knowledge or hypothesis concerning drug fate and disposition. This is a
      great advantage of the method considered here when compared with compartment
      methods. The research presented in this study was aimed at contributing to the
      knowledge base of physiological origins of mean residence times. 

PMID- 24334532
TI  - beta3-Adrenoceptor-mediated responses in diabetic rat heart.
AB  - beta3-adrenoceptors mediate negative inotropic effect in contrast to classical
      beta1- and beta2-adrenoceptors. Cardiac beta3-adrenoceptors are upregulated in
      experimental diabetes. Thus, cardiodepressant effect mediated by beta3
      adrenoceptors has been proposed to contribute to the impaired cardiac function in
      this pathology. In our study, we investigated the influence of streptozotocin
      diabetes on cardiac contractility to beta3-adrenoceptors stimulation by using
      Langendorff-perfused rat hearts. BRL 37344, a selective beta3-adrenoceptor
      agonist, induced dose-dependent decreases in left ventricular developed pressure
      (LVDP) in hearts from control rats. BRL 37344 also dose-dependently decreased
      +dP/dt and -dP/dt values. Effects of BRL 37344 were abolished by SR 59230, but
      not altered by nadolol pre-treatment. On the other hand, these effects of BRL
      37344 were all significantly increased in hearts from diabetic rats. We also
      observed that diabetes significantly increased the mRNA levels encoding cardiac
      beta3-adrenoceptors. In addition, Gialpha2 mRNA expressions were found to be
      increased in the cardiac tissue of diabetic rats as well. The effect of BRL 37344
      on cardiac contractility was normalized upon treatment of diabetic rats with
      insulin. These data demonstrate an increased effect of beta3-adrenoceptor
      stimulation on hemodynamic function of the heart in accordance with an increased
      mRNA levels encoding cardiac beta3-adrenoceptors in 8-week diabetic rats. 

PMID- 24334533
TI  - Extremely low frequency magnetic fields induce oxidative stress in rat brain.
AB  - The present investigation was conducted to understand the influence of long-term
      exposure of rats to extremely low frequency magnetic fields (ELF-MF), focusing on
      oxidative stress (OS) on different regions of rat's brain. Male Wistar rats (21
      day-old) were exposed to ELF-MF (50 Hz; 50 and 100 uT) for 90 days continuously;
      hippocampal, cerebellar and cortical regions from rats were analyzed for (i)
      reactive oxygen species (ROS), (ii) metabolites indicative of OS and (iii)
      antioxidant enzymes. In comparison to control group rats, the rats that were
      continuously exposed to ELF-MF caused OS and altered glutathione (GSH/GSSG)
      levels in dose-dependent manner in all the regions of the brain. Accumulation of
      ROS, lipid peroxidation end products and activity of superoxide dismutase in
      different regions was in the descending order of cerebellum < hippocampus <
      cortex. Decrement in GSH/GSSG levels and increment in glutathione peroxidase
      activity were in the descending order of hippocampus < cerebellum < cortex. The
      continuous exposure to ELF-MF caused OS in all the examined regions of brain more
      significantly at 100 uT than at 50 uT. Varied influences observed in different
      regions of the brain, as documented in this study, may contribute to altered
      metabolic patterns in its related regions of the central nervous system, leading
      to aberrant neuronal functions.

PMID- 24334534
TI  - Mitochondrial oxidative energy metabolism in guanethidine-induced
      sympathectomized ducklings.
AB  - Here we investigate the possible involvement of the sympathetic nervous system in
      the respiratory properties of intermyofibrillar and subsarcolemmal mitochondrial
      populations from heart and gastrocnemius muscles. Mitochondrial oxidative
      phosphorylation was assessed polarographically by using succinate (plus
      rotenone), and ascorbate plus N,N,N',N'-tetramethyl-p-phenyl-enediamine (plus
      antimycin) as respiratory substrates. We report that chronic chemical
      sympathectomy with guanethidine (150 mg/kg, daily for 3 weeks) induced a marked
      decrease in whole body metabolic and heart rates, in plasma metabolites (fatty
      acids and glucose) and norepinephrine levels. Guanethidine treatment decreased
      mainly the oxidative phosphorylation capacity of subsarcolemmal mitochondria in
      heart, irrespective of the substrate used. In contrast, both mitochondrial
      populations were affected by the treatment in skeletal muscle. This suggests that
      sympathetic nervous system activity can alter the energetic status of muscle
      cells, and to some extent play a thermogenic role in birds. 

PMID- 24334535
TI  - Reply on 'Comparative evaluation of two dose optimization methods for image
      guided, highly-conformal, tandem and ovoids cervix brachytherapy planning'.

PMID- 24334536
TI  - Discussion about several potential drawbacks of PEGylated therapeutic proteins.
AB  - PEGylation changes the physical and chemical properties of the biomedical
      molecule, such as its conformation, electrostatic binding, and hydrophobicity,
      and results in an improvement in the pharmacokinetic behavior of the drug, while
      it also causes some disadvantages of which cannot be neglected. The available
      data manifests that polyethylene glycol (PEG) itself shows potential risk, such
      as immunogenicity of the PEG and PEG-containing vacuoles in cells observed with
      PEGylated biologicals. Decreased activity and heterogeneity are also the negative
      aspects of PEGylation. The unfavorable impacts which are brought by the
      PEGylation are described here with examples of modified therapeutic proteins on
      the market and used in the clinical trials. 

PMID- 24334537
TI  - An efficient method for differentiation of human induced pluripotent stem cells
      into hepatocyte-like cells retaining drug metabolizing activity.
AB  - The use of human induced pluripotent stem (iPS) cells would be of great value for
      a variety of applications involving drug development studies. Several reports
      have been published on the differentiation of human iPS cells into hepatocyte
      like cells; however, the cells were insufficient for application in drug
      metabolism studies. In this study, we aimed to establish effective methods for
      differentiation of human iPS cells into hepatocytes. Two human iPS cell lines
      were differentiated by addition of activin A, dimethyl sulfoxide, hepatocyte
      growth factor, oncostatin M, and dexamethasone. The differentiated cells
      expressed hepatocyte markers and drug-metabolizing enzymes, revealing that the
      human iPS cells were differentiated into hepatocyte-like cells. Expression of
      CYP3A4 and UGT1A1 mRNAs increased with treatment with typical inducers of the
      enzymes, and the response of the cells against the inducers was similar to that
      of human hepatocytes. Furthermore, the drug-metabolizing activity of CYP3A4, as
      monitored by testosterone 6beta-hydroxylase activity, was elevated by these
      inducers. In conclusion, we established methods for differentiation of hepatocyte
      like cells expressing drug metabolizing activity from human iPS cells. The
      hepatocyte-like cells derived from human iPS cells will be useful for drug
      metabolism studies. 

PMID- 24334538
TI  - Functional characteristics of aquaporin 7 as a facilitative glycerol carrier.
AB  - Aquaglyceroporins, which constitute a subgroup of aquaporin (AQP) water channels,
      had been believed to serve as channels for glycerol as well as for water.
      However, our recent studies have indicated that AQP9 and AQP10 operate in a
      carrier mode, which is of saturable nature, for glycerol transport. Assuming that
      such a functional characteristic could also be shared by AQP7, another
      aquaglyceroporin, we examined its glycerol transport function. The specific
      transport of glycerol by human AQP7, which was stably expressed in Madin-Darby
      canine kidney II cells, was indeed highly saturable, indicating the involvement
      of a carrier mode of operation mechanism. Kinetic analysis indicated that the
      specific transport conformed to Michaelis-Menten kinetics with the Michaelis
      constant of 11.9 uM and was not associated with a nonsaturable transport
      component as an indication of a simultaneous channel mode of operation, which was
      previously indicated for AQP10. AQP7-specific glycerol transport was furthermore
      found to be specifically inhibited by several compounds analogous to glycerol and
      operate without requiring either Na(+) or H(+). These characteristics of the
      carrier mode of AQP7 operation suggest that it is a facilitative carrier for
      glycerol and, possibly, also for analogous compounds, providing a novel insight
      into its operation mechanism. 

PMID- 24334540
TI  - (On)line dancing: choosing an appropriate distance education partner.
AB  - Online-delivered distance education is a burgeoning component of professional
      development and continuing education. Distance education programs allow
      individuals to learn in a different location and/or at a different time from
      fellow learners, thereby increasing the flexibility and number of learning
      options. Selecting the "right" program for personal development from the ever
      growing body of online-delivered education is an individualized decision that can
      become an overwhelming and challenging process. This Tool presents four important
      definitions for navigating distance education program description materials and
      outlines a five-step process to assist in identifying an appropriate program for
      personal development. The five-step process includes key questions and points to
      consider while conducting a candid self-assessment, identifying and investigating
      distance education programs, and then compiling information, comparing programs,
      and prioritizing a list of programs suitable for application. Furthermore, this
      Tool highlights important websites for distance education degree program reviews,
      accreditation information, and open educational resources. 

PMID- 24334539
TI  - Clinical application of multimodality imaging in radiotherapy treatment planning
      for rectal cancer.
AB  - Radiotherapy plays an important role in the treatment of rectal cancer. Three
      dimensional conformal radiotherapy and intensity-modulated radiotherapy are
      mainstay techniques of radiotherapy for rectal cancer. However, the success of
      these techniques is heavily reliant on accurate target delineation and treatment
      planning. Computed tomography simulation is a cornerstone of rectal cancer
      radiotherapy, but there are limitations, such as poor soft-tissue contrast
      between pelvic structures and partial volume effects. Magnetic resonance imaging
      and positron emission tomography (PET) can overcome these limitations and provide
      additional information for rectal cancer treatment planning. PET can also reduce
      the interobserver variation in the definition of rectal tumor volume. However,
      there is a long way to go before these image modalities are routinely used in the
      clinical setting. This review summarizes the most promising studies on clinical
      applications of multimodality imaging in target delineation and treatment
      planning for rectal cancer radiotherapy. 

PMID- 24334541
TI  - Measuring the progress of capacity building in the Alberta Policy Coalition for
      Cancer Prevention.
AB  - The Alberta Policy Coalition for Cancer Prevention (APCCP) represents
      practitioners, policy makers, researchers, and community organizations working
      together to coordinate efforts and advocate for policy change to reduce chronic
      diseases. The aim of this research was to capture changes in the APCCP's capacity
      to advance its goals over the course of its operation. We adapted the Public
      Health Agency of Canada's validated Community Capacity-Building Tool to capture
      policy work. All members of the APCCP were invited to complete the tool in 2010
      and 2011. Responses were analyzed using descriptive statistics and t tests.
      Qualitative comments were analyzed using thematic content analysis. A group
      process for reaching consensus provided context to the survey responses and
      contributed to a participatory analysis. Significant improvement was observed in
      eight out of nine capacity domains. Lessons learned highlight the importance of
      balancing volume and diversity of intersectoral representation to ensure
      effective participation, as well as aligning professional and economic resources.
      Defining involvement and roles within a coalition can be a challenging activity
      contingent on the interests of each sector represented. The participatory
      analysis enabled the group to reflect on progress made and future directions for
      policy advocacy. 

PMID- 24334542
TI  - Implementation and evaluation of the HEROES initiative: a tri-state coordinated
      school health program to reduce childhood obesity.
AB  - This article describes the design, implementation, and evaluative findings of the
      HEROES (Healthy, Energetic, Ready, Outstanding, Enthusiastic, Schools)
      Initiative, a school-based multilevel childhood obesity prevention intervention.
      Based on the Centers for Disease Control and Prevention's recommended coordinated
      school health approach, the HEROES Initiative works to alleviate the burden of
      childhood obesity in Southern Indiana, Northwestern Kentucky, and Southeastern
      Illinois in the United States. Process evaluation was conducted with the 17
      participating schools in spring 2012 based on interviews with school personnel
      and observation of the school environment. Findings showed that despite some
      variability, schools were generally able to implement the intervention with
      fidelity. School-level outcome evaluation was also based on observation of the
      school environment, and revealed that schools had implemented a number of new
      practices to encourage physical activity and healthy eating. Assessment of
      student-level outcomes was based on professionally collected physiological
      measurements and self-reported behavioral data collected over an 18-month period
      of time, last collected in spring 2012. Findings demonstrated that the HEROES
      Initiative has been successful in reducing the percentage of overweight children
      in participating schools and healthfully modifying their dietary, physical
      activity, and sedentary behaviors. Strategies that have facilitated success and
      challenges related to the intervention are discussed. 

PMID- 24334544
TI  - Barriers to bicycle helmet use in young children in an urban elementary school.
AB  - PURPOSE: Traumatic brain injury is a leading cause of death in bicycle crashes.
      The factors associated with bicycle helmet use in young children with diverse
      ethnic and socioeconomic backgrounds have not been studied. The purpose of this
      study was to identify barriers to helmet use in young children in an urban
      elementary school. DESIGN: Qualitative content analysis with semistructured
      interviews, observational field notes, and artifacts. SETTING: Urban elementary
      school. PARTICIPANTS: Seventeen students whose age ranged from 5 to 7 years and
      whose ethnic background was identified as African American (14) or Caucasian (3).
      METHOD: Children participated in a brain safety fair that included presentations
      and activities. Semistructured, pre- and postexperience interviews were
      completed. Observations of the students participating in the activities and
      reflective art projects from the students were collected. RESULTS: The analysis
      found the following barriers to helmet use: (a) lack of access to a helmet, (b)
      poor fit of helmets due to hairstyles, and (c) lack of knowledge regarding helmet
      use. CONCLUSION: The present study suggests that the issue of helmet design and
      comfort for younger children with variable hairstyles needs to be addressed in
      order to increase helmet use in this population.

PMID- 24334545
TI  - Synthesis and photoluminescence properties of La2Zr2O7:Eu3+@YBO3 core@shell
      nanoparticles.
AB  - Novel heterostructured La2Zr2O7:Eu(3+)@YBO3 core@shell nanoparticles (NPs)
      composed of a trivalent europium doped lanthanum zirconate (La2Zr2O7:Eu(3+)) core
      and yttrium orthoborate (YBO3) shell are reported in this paper for the first
      time. X-ray diffraction, Fourier transform infrared spectroscopy, scanning and
      transmission electron microscopies, and x-ray photoelectron spectroscopy were
      employed to confirm the formation of the heterostructured core@shell NPs.
      Luminescent enhancement was observed after the La2Zr2O7:Eu(3+) core NPs were
      coated with the thin YBO3 shells under 405 nm excitation. Based on optical
      transition property analysis and fluorescent decay measurement, the reduction of
      non-radiative transition rate is possibly responsible for the luminescent
      enhancement. Moreover, an improvement of the symmetry around the Eu(3+) ions in
      the La2Zr2O7:Eu(3+) core NPs was found after the YBO3 shell coating. 

PMID- 24334543
TI  - Results from a pilot promotora program to reduce depression and stress among
      immigrant Latinas.
AB  - The stressful experiences that Latino immigrants face throughout the migration
      process to the United States put them at increased risk for poor mental health.
      Latinas are at heightened risk due to stigma, limited access to mental health
      resources, domestic violence, and gender role expectations. In addition, for
      those who live in new immigrant settlement areas, such as the Southeast, these
      disparities are magnified by even fewer culturally appropriate services and
      limited social support. This study evaluates the impact of ALMA (Amigas Latinas
      Motivando el Alma/Latina Friends Motivating the Soul), a pilot promotora
      intervention offered in three North Carolina counties to improve mental health
      among Latinas by offering coping skills training. The intervention trained
      community-based promotoras to conduct outreach to Latina women in their social
      network (companeras). Using a pre-post test design, we assessed the mental health
      outcomes of companeras. Companeras improved on the following outcomes: depressive
      symptoms, attitudes of depression treatment, perceived and acculturative stress,
      perceived social support, and positive coping responses. Our findings suggest
      that promotora interventions, such as ALMA, that focus on building self-care
      strategies can be valuable to reducing preclinical symptoms and addressing health
      care disparities that are exacerbated by unavailable or underused mental health
      services. 

PMID- 24334546
TI  - BNF recommendations for the treatment of Wernicke's encephalopathy: lost in
      translation?

PMID- 24334547
TI  - Nonlinear hydrodynamic theory of crystallization.
AB  - We present an isothermal fluctuating nonlinear hydrodynamic theory of
      crystallization in molecular liquids. A dynamic coarse-graining technique is used
      to derive the velocity field, a phenomenology which allows a direct coupling
      between the free energy functional of the classical density functional theory and
      the Navier-Stokes equation. In contrast to the Ginzburg-Landau type amplitude
      theories, the dynamic response to elastic deformations is described by parameter
      free kinetic equations. Employing our approach to the free energy functional of
      the phase-field crystal model, we recover the classical spectrum for the phonons
      and the steady-state growth fronts. The capillary wave spectrum of the
      equilibrium crystal-liquid interface is in good qualitative agreement with the
      molecular dynamics simulations. 

PMID- 24334548
TI  - Aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in
      tumor-producing MMTV-PyVT mice.
AB  - Aquaporin 1 (AQP1) is a plasma membrane water-transporting protein expressed
      strongly in tumor microvascular endothelia. We previously reported impaired
      angiogenesis in implanted tumors in AQP1-deficient mice and reduced migration of
      AQP1-deficient endothelial cells in vitro. Here, we investigated the consequences
      of AQP1 deficiency in mice that spontaneously develop well-differentiated,
      luminal-type breast adenomas with lung metastases [mouse mammary tumor virus
      driven polyoma virus middle T oncogene (MMTV-PyVT)]. AQP1(+/+) MMTV-PyVT mice
      developed large breast tumors with total tumor mass 3.5 +/- 0.5 g and volume 265
      +/- 36 mm(3) (SE, 11 mice) at age 98 d. Tumor mass (1.6+/-0.2 g) and volume
      (131+/-15 mm(3), 12 mice) were greatly reduced in AQP1(-/-) MMTV-PyVT mice
      (P<0.005). CD31 immunofluorescence showed abnormal microvascular anatomy in
      tumors of AQP1(-/-) MMTV-PyVT mice, with reduced vessel density. HIF-1alpha
      expression was increased in tumors in AQP1(-/-) MMTV-PyVT mice. The number of
      lung metastases (5+/-1/mouse) was much lower than in AQP1(+/+) MMTV-PyVT mice
      (31+/-8/mouse, P<0.005). These results implicate AQP1 as an important determinant
      of tumor angiogenesis and, hence, as a potential drug target for adjuvant therapy
      of solid tumors.

PMID- 24334549
TI  - Single-fluorophore biosensors based on conformation-sensitive GFP variants.
AB  - The beta-strands of GFP form a rigid barrel that protects the chromophore from
      external influence. Herein, we identified specific mutations in beta-strand 7
      that render the chromophore sensitive to interactions of GFP with another protein
      domain. In the process of converting the FRET-based protein kinase A (PKA) sensor
      AKAR2 into a single-wavelength PKA sensor containing a GFP and a quencher, we
      discovered that the quencher was not required and that the sensor response relied
      on changes in GFP intrinsic fluorescence. The identified mutations in beta-strand
      7 render GFP fluorescence intensity and lifetime sensitive to conformational
      changes of the PKA-sensing domain. In addition, sensors engineered from the
      GCaMP2 calcium indicator to incorporate a conformation-sensitive GFP (csGFP)
      exhibited calcium-dependent fluorescence changes. We further demonstrate that
      single GFP sensors report PKA dynamics in dendritic spines of neurons from brain
      slices on 2-photon imaging with a high signal-to-baseline ratio and minimal
      photobleaching. The susceptibility of GFP variants to dynamic interactions with
      other protein domains provides a new approach to generate single wavelength
      biosensors for high-resolution imaging.

PMID- 24334550
TI  - Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte
      meiosis.
AB  - Sirtuins have been widely reported to be involved in multiple biological
      processes; however, their function in oocyte meiosis has not been. Here, by
      confocal scanning and quantitative analysis, we show that specific depletion of
      Sirt2 in mouse oocytes results in spindle defects and chromosome disorganization
      (35.5+/-8.7 vs. 9.6+/-3.8% control; P<0.05), with impaired microtubule
      kinetochore interaction. Moreover, knockdown and overexpression experiments
      reveal that Sirt2 modulates the acetylation status of histone H4K16 and alpha
      tubulin in oocytes, which may in part mediate the defective phenotypes described
      above by influencing microtubule dynamics and kinetochore function. Finally, we
      find lower Sirt2 protein level in oocytes from aged mice by immunoblotting and
      that maternal age-associated meiotic defects can be ameliorated through
      overexpression of Sirt2 (33.2+/-5.1% old vs.12.7+/-5.2% old+Sirt2; P<0.05),
      providing support for the hypothesis that decreased Sirt2 is one of a number of
      factors contributing to oocyte age-dependent deficits. In summary, our data
      indicate a role for Sirt2 during oocyte meiosis and uncover a striking beneficial
      effect of increased Sirt2 expression on aged oocytes.

PMID- 24334551
TI  - Cardiac tissue engineering in magnetically actuated scaffolds.
AB  - Cardiac tissue engineering offers new possibilities for the functional and
      structural restoration of damaged or lost heart tissue by applying cardiac
      patches created in vitro. Engineering such functional cardiac patches is a
      complex mission, involving material design on the nano- and microscale as well as
      the application of biological cues and stimulation patterns to promote cell
      survival and organization into a functional cardiac tissue. Herein, we present a
      novel strategy for creating a functional cardiac patch by combining the use of a
      macroporous alginate scaffold impregnated with magnetically responsive
      nanoparticles (MNPs) and the application of external magnetic stimulation.
      Neonatal rat cardiac cells seeded within the magnetically responsive scaffolds
      and stimulated by an alternating magnetic field of 5 Hz developed into matured
      myocardial tissue characterized by anisotropically organized striated cardiac
      fibers, which preserved its features for longer times than non-stimulated
      constructs. A greater activation of AKT phosphorylation in cardiac cell
      constructs after applying a short-term (20 min) external magnetic field indicated
      the efficacy of magnetic stimulation to actuate at a distance and provided a
      possible mechanism for its action. Our results point to a synergistic effect of
      magnetic field stimulation together with nanoparticulate features of the scaffold
      surface as providing the regenerating environment for cardiac cells driving their
      organization into functionally mature tissue.

PMID- 24334552
TI  - An independent system for real-time dynamic multileaf collimation trajectory
      verification using EPID.
AB  - A new tool has been developed to verify the trajectory of dynamic multileaf
      collimators (MLCs) used in advanced radiotherapy techniques using only the
      information provided by the electronic portal imaging devices (EPID) measured
      image frames. The prescribed leaf positions are resampled to a higher resolution
      in a pre-processing stage to improve the verification precision. Measured MLC
      positions are extracted from the EPID frames using a template matching method. A
      cosine similarity metric is then applied to synchronise measured and planned leaf
      positions for comparison. Three additional comparison functions were incorporated
      to ensure robust synchronisation. The MLC leaf trajectory error detection was
      simulated for both intensity modulated radiation therapy (IMRT) (prostate) and
      volumetric modulated arc therapy (VMAT) (head-and-neck) deliveries with
      anthropomorphic phantoms in the beam. The overall accuracy for MLC positions
      automatically extracted from EPID image frames was approximately 0.5 mm. The MLC
      leaf trajectory verification system can detect leaf position errors during IMRT
      and VMAT with a tolerance of 3.5 mm within 1 s. 

PMID- 24334553
TI  - In vivo antinociceptive and anticonvulsant activity of extracts of Heliotropium
      strigosum.
AB  - Natural healing agents are primarily focused to overcome unwanted side effects
      with synthetic drugs worldwide. In the proposed study, crude extracts and
      subsequent solvent fractions of Heliotropium strigosum were evaluated for
      antinociceptive and anticonvulsant activity in animal paradigms. In post acetic
      acid-induced writhing test, crude extract and fractions (hexane, ethyl acetate,
      and aqueous) demonstrated marked attenuation of nociception at test doses (50,
      100, and 200 mg/kg i.p.). When challenged against thermally induced pain model,
      pretreatment of extracts exhibited prominent amelioration at test dose (50, 100,
      and 200 mg/kg i.p.). In both tests, inhibition of noxious stimulation was in a
      dose-dependent manner, and ethyl acetate fraction was most dominant. However,
      extracts did not antagonize the seizures and mortality induced by
      pentylenetetrazole. In conclusion, the extracts of H. strigosum illustrated
      significant antinociceptive effect in both centrally and peripherally acting pain
      models. 

PMID- 24334554
TI  - Ten-year long-term results of total joint arthroplasties with ARPE(r) implant in
      the treatment of trapeziometacarpal osteoarthritis.
AB  - Between May 1999 and April 2002 a total of 69 consecutive thumb carpometacarpal
      joint arthoplasties were performed in a total of 64 patients for carpometacarpal
      joint osteoarthritis using the cementless hydroxyapatite (HA)-coated
      unconstrained ARPE implant. Clinical, functional and radiological results at 10
      year follow-up are presented. Survival analysis was performed using the Kaplan
      Meier method. Of the 64 patients, four were lost to follow-up, 60 implants
      (92.3%) were functional and five (7.7%) were not (two dislocated, two were
      removed and one with aseptic loosening). Survival estimate for functional
      implants over 10 years was 93.9% (95% confidence interval 82.3-97.9). The
      radiographs were satisfactory in 82.4%. There was subsidence of the cup in 15.8%.
      Thumb carpometacarpal joint arthroplasty with the ARPE implant offers a reliable
      treatment alternative in patients with Eaton grade III or IV thumb
      carpometacarpal joint arthritis in the presence of good bone stock. 

PMID- 24334555
TI  - Surgical rehabilitation for correction of severe flexion contracture of the
      proximal interphalangeal joint by modified Ilizarov method.

PMID- 24334556
TI  - Anatomic course of the medial antebrachial cutaneous nerve: a cadaveric study
      with proposed clinical application in failed cubital tunnel release.

PMID- 24334557
TI  - Assessment of elevation of and rapid change in left ventricular filling pressure
      using a novel global strain imaging diastolic index.
AB  - BACKGROUND: The aim of this study was to determine whether global strain imaging
      diastolic index (SIDI) obtained using 2-D speckle tracking imaging (2DSI) could
      predict elevation in and rapid change of LV filling pressure. METHODS AND
      RESULTS: Patients (n=126) underwent echocardiography and 2DSI during simultaneous
      cardiac catheterization. There were 60 patients in whom the same measurements
      were repeated 5min after i.v. glyceryl trinitrate. LV pre-atrial contraction
      pressure (pre-A) was measured as a surrogate of LV filling pressure. SIDI was
      defined as the change of LV longitudinal strain measured using 2DSI during the
      first one-third of diastole. Then, longitudinal global SIDI (L-global SIDI) was
      calculated as the mean SIDI of 18 LV segments. Mitral inflow and tissue Doppler
      imaging were also assessed. Among 126 patients, 93 patients had LV pre-A
      >=15mmHg. L-global SIDI had a better correlation with LV pre-A (P<0.001, r=-0.56)
      than E/e' (P<0.01, r=0.35). On receiver operating characteristic curve analysis,
      L-global SIDI <0.48 was the optimum cut-off to predict LV pre-A >=15mmHg
      (sensitivity, 82%; specificity, 68%). In addition, the ratio of L-global SIDI
      (after nitrate/before nitrate) was correlated with the ratio of LV pre-A (after
      nitrate/before nitrate; P=0.02, r=-0.34). CONCLUSIONS:  A novel L-global SIDI
      derived from 2DSI may reflect elevated LV filling pressure and its rapid change
      better than conventional diastolic parameters. 

PMID- 24334558
TI  - Vessel bioengineering.
AB  - The development of vascular bioengineering has led to a variety of novel
      treatment strategies for patients with cardiovascular disease. Notably, combining
      biodegradable scaffolds with autologous cell seeding to create tissue-engineered
      vascular grafts (TEVG) allows for in situ formation of organized neovascular
      tissue and we have demonstrated the clinical viability of this technique in
      patients with congenital heart defects. The role of the scaffold is to provide a
      temporary 3-dimensional structure for cells, but applying TEVG strategy to the
      arterial system requires scaffolds that can also endure arterial pressure. Both
      biodegradable synthetic polymers and extracellular matrix-based natural materials
      can be used to generate arterial scaffolds that satisfy these requirements.
      Furthermore, the role of specific cell types in tissue remodeling is crucial and
      as a result many different cell sources, from matured somatic cells to stem
      cells, are now used in a variety of arterial TEVG techniques. However, despite
      great progress in the field over the past decade, clinical effectiveness of small
      diameter arterial TEVG (<6mm) has remained elusive. To achieve successful
      translation of this complex multidisciplinary technology to the clinic, active
      participation of biologists, engineers, and clinicians is required.

PMID- 24334559
TI  - Minimizing contrast dose according to estimated glomerular filtration rate.

PMID- 24334560
TI  - Pregnancy-related obstetric and cardiologic problems in women after atrial switch
      operation for transposition of the great arteries.
AB  - BACKGROUND: The number of women with congenital heart disease reaching
      reproductive age has increased due to therapeutic advances. The aim of this study
      was to examine obstetric and cardiac problems during pregnancy after
      Mustard/Senning repair for transposition of the great arteries. METHODS AND
      RESULTS: Sixty pregnancies in 34 women from 3 centers were studied. The women
      were interviewed, and their records reviewed for clinical status and diagnostic
      evaluation. Age range was 16-34 years during first pregnancy, and all were in a
      low functional class. There were 11 miscarriages and 5 abortions. Of 44
      successful pregnancies, 20 were vaginal deliveries and 24, cesarean sections. A
      total of 25% were delivered prematurely. Thirteen babies had birth weight
      <2,500g. Deterioration in functional class occurred in 7 pregnancies, without
      recovery in 5. Deterioration in systolic function occurred in 4 of 44
      echocardiographically documented pregnancies, without recovery in 75%. In 2 women
      resuscitation was necessary during delivery, in 1, supraventricular tachycardia
      occurred during labor. CONCLUSIONS: Pregnancy is usually well-tolerated, but
      outcome is unforeseeable and life-threatening problems can occur. These women
      belong in cardiac care conducted by experienced congenital cardiologists, who
      systematically check for typical residua. The pregnancy should be planned and
      gynecologists/obstetricians with special expertise integrated into the
      consultations. During delivery a congenital cardiologist, and an anesthetist
      experienced in congenital cardiology, should be present for possible severe
      cardiac events.

PMID- 24334561
TI  - Antiplatelet therapy in patients with diabetes mellitus and acute coronary
      syndrome.
AB  - Patients with diabetes mellitus have increased atherothrombotic risk and elevated
      rates of recurrent cardiac events, which may be in part attributable to
      abnormalities of platelet function resulting in increased platelet reactivity.
      Despite improved clinical outcomes with an antiplatelet strategy of aspirin plus
      clopidogrel in patients with acute coronary syndrome (ACS), diabetic patients
      continue to experience relatively high rates of adverse events during follow-up.
      Thus, strategies using more potent antiplatelet drugs are warranted in diabetic
      patients with ACS, especially in the presence of an increased coronary
      angiographic risk profile. The relative benefit of prasugrel has been described
      as higher in diabetic vs. nondiabetic patients, without increase in the bleeding
      risk, whereas a reduction in ischemic events was similar with ticagrelor in
      patients with and without diabetes. Glycoprotein IIb/IIIa inhibitors are
      indicated in high-risk patients with ACS, but diabetic patients do not benefit
      from routine administration of such agents.

PMID- 24334563
TI  - Patchiness of ion-exchanged mica revealed by DNA binding dynamics at short length
      scales.
AB  - The binding of double-stranded (ds) DNA to mica can be controlled through ion
      exchanging the mica with divalent cations. Measurements of the end-to-end
      distance of linear DNA molecules discriminate whether the binding mechanism
      occurs through 2D surface equilibration or kinetic trapping. A range of linear
      dsDNA fragments have been used to investigate length dependences of binding.
      Mica, ion-exchanged with Ni(II) usually gives rise to kinetically trapped DNA
      molecules, however, short linear fragments (<800 bp) are seen to deviate from the
      expected behaviour. This indicates that ion-exchanged mica is heterogeneous, and
      contains patches or domains, separating different ionic species. These results
      correlate with imaging of dsDNA under aqueous buffer on Ni(II)-mica and indicate
      that binding domains are of the order of 100 nm in diameter. Shorter DNA
      fragments behave intermediate to the two extreme cases of 2D equilibration and
      kinetic trapping. Increasing the incubation time of Ni(II) on mica, from minutes
      to hours, brings the conformations of the shorter DNA fragments closer to the
      theoretical value for kinetic trapping, indicating that long timescale kinetics
      play a role in ion-exchange. X-ray photoelectron spectroscopy (XPS) was used to
      confirm that the relative abundance of Ni(II) ions on the mica surface increases
      with time. These findings can be used to enhance spatial control of binding of
      DNA to inorganic surfaces with a view to patterning high densities arrays. 

PMID- 24334562
TI  - Functional imaging biomarkers for assessing response to treatment in liver and
      lung metastases.
AB  - Management of patients with metastatic cancer and development of new treatments
      rely on imaging to provide non-invasive biomarkers of tumour response and
      progression. The widely used size-based criteria have increasingly become
      inadequate where early measures of response are required to avoid toxicity of
      ineffective treatments, as biological, physiologic, and molecular modifications
      in tumours occur before changes in gross tumour size. A multiparametric approach
      with the current range of imaging techniques allows functional aspects of tumours
      to be simultaneously interrogated. Appropriate use of these imaging techniques
      and their timing in relation to the treatment schedule, particularly in the
      context of clinical trials, is fundamental. There is a lack of consensus
      regarding which imaging parameters are most informative for a particular disease
      site and the best time to image so that, despite an increasing body of
      literature, open questions on these aspects remain. In addition, standardization
      of these new parameters is required. This review summarizes the published
      literature over the last decade on functional and molecular imaging techniques in
      assessing treatment response in liver and lung metastases. 

PMID- 24334564
TI  - N-terminal pro-brain natriuretic peptide as a predictor of reoperation in
      children with surgically corrected tetralogy of fallot.
AB  - BACKGROUND:  Most patients with surgically corrected tetralogy of Fallot (TOF)
      are faced with multiple residua and sequelae such as pulmonary regurgitation
      (PR), resulting in reoperation for pulmonary valve replacement (PVR). Plasma
      brain natriuretic peptide (BNP) level and serum N-terminal pro-BNP (NT-pro-BNP)
      level are useful as diagnostic objective markers of chronic heart failure (CHF).
      The aim of the study was to examine whether these markers have predictive ability
      for reoperation in children with surgically corrected TOF. METHODS AND RESULTS: 
      Fifty-eight patients (38 male, 20 female) aged 1-18 years (median, 7 years) were
      enrolled. Serum NT-pro-BNP in TOF patients was significantly higher than in age
      matched hospital controls without CHF (359.5+/-449.7pg/ml vs. 86.1+/-45.1pg/ml,
      respectively; P<0.0001). BNP and NT-pro-BNP had a better correlation with CHF
      index, RVEDP, and LVEDV in TOF groups. Children with surgically corrected TOF who
      had indication for PVR had higher BNP and NT-pro-BNP and more severe PR than
      those without indication for PVR. On multivariate logistic regression analysis,
      NT-pro-BNP was the strongest predictor for reoperation in patients with
      surgically corrected TOF. Area under the curve of NT-pro-BNP for reoperation was
      0.950 (P<0.001) with a sensitivity of 88.9% and specificity of 91.8%.
      CONCLUSIONS:  NT-pro-BNP is a good biomarker for monitoring CHF, and is a good
      predictor of PVR in children with surgically repaired TOF. 

PMID- 24334565
TI  - Robot-assisted minimally invasive direct coronary artery bypass grafting.
      ThoraCAB.
AB  - BACKGROUND:  The aim of this study was to assess the outcome of robot-assisted
      minimally invasive direct coronary artery bypass grafting (MIDCAB), which is also
      termed "ThoraCAB". METHODS AND RESULTS:  From 2005 to 2013, 35 consecutive
      patients underwent MIDCAB via a small thoracotomy on a beating heart. Before
      performing MIDCAB, the internal thoracic arteries (ITAs) were endoscopically
      harvested through 3 ports using the da Vinci Surgical System in a completely
      skeletonized fashion. Distal anastomosis was hand-sewn using a vacuum stabilizer,
      and a coronary artery active perfusion system was used to prevent myocardial
      ischemia during anastomosis. Successful robot-assisted ITA harvesting was
      achieved in all patients. There was an average of 1.7+/-0.8 grafts (range, 1-3
      grafts) per patient. No patient needed mechanical ventilation for more than 24h.
      There were no deaths, strokes or myocardial infarctions, and none of the patients
      required conversion to median sternotomy. CONCLUSIONS:  Robot-assisted ITA
      harvesting is safe and feasible. ThoraCAB is a relatively simple procedure and
      allows multivessel bypass grafting after a small thoracotomy. Therefore, it is
      expected that ThoraCAB will become the standard procedure for minimally invasive
      coronary revascularization and will be used in totally endoscopic CABG in the
      future. 

PMID- 24334566
TI  - A first-principles study of As doping at a disordered Si-SiO2 interface.
AB  - Understanding the interaction between dopants and semiconductor-oxide interfaces
      is an increasingly important concern in the drive to further miniaturize modern
      transistors. To this end, using a combination of first-principles density
      functional theory and a continuous random network Monte Carlo method, we
      investigate electrically active arsenic donors at the interface between silicon
      and its oxide. Using a realistic model of the disordered interface, we find that
      a small percentage (on the order of ~10%) of the atomic sites in the first few
      monolayers on the silicon side of the interface are energetically favourable for
      segregation, and that this is controlled by the local bonding and local strain of
      the defect centre. We also find that there is a long-range quantum confinement
      effect due to the interface, which results in an energy barrier for dopant
      segregation, but that this barrier is small in comparison to the effect of the
      local environment. Finally, we consider the extent to which the energetics of
      segregation can be controlled by the application of strain to the interface. 

PMID- 24334567
TI  - Growth of straight one-dimensional Ge/ZnSe heterojunctions with atomically sharp
      interfaces by catalytic residue controls.
AB  - One-dimensional (1D) heteroepitaxy with an abrupt interface is essential to
      construct the 1D heterojunctions required for photonic and electronic devices.
      During catalytic 1D heteroepitaxial growth, however, the heterojunctions are
      generically kinked and composition-diffused across the interfaces. Here, we
      report a simple synthetic route for straight 1D heteroepitaxy with atomically
      sharp interfaces of group IV(Ge)/group II-VI(ZnSe) nanowires (NWs) during Au
      catalytic growth. Specifically, it is discovered that eliminating residues in Au
      catalysts by Se vapour treatments lowers the energy barrier for the Ge NW axial
      heteroepitaxy on ZnSe NWs, and forms atomically abrupt heterointerfaces. We
      verified such 1D variation in the local electronic band structure of the grown
      Ge/ZnSe NW heterojunctions with spatially resolved photocurrent measurements. 

PMID- 24334568
TI  - Malignant abdominal rocks: where do they come from?
AB  - For the radiologist, calcifications in an abdominal malignancy raise questions of
      both diagnostic and prognostic significance. Although certain cancers are well
      known to calcify, such as colorectal and ovarian, malignant abdominal
      calcifications actually arise from a wide variety of epithelial, mesenchymal,
      lymphoid, or germ cell neoplasms. The pathophysiology of calcification in
      abdominal malignancies is heterogeneous and incompletely understood.
      Calcifications may present primarily, in untreated tumors, or develop during
      treatment; the latter can occur in variable clinical settings. A basic
      understanding of the varied pathogenic etiology can assist the radiologist in
      assessing disease status. By presenting an assortment of calcified abdominal
      malignancies on computed tomography in varied clinical settings, we aim not only
      to inform the differential diagnosis, but also to clarify the prognosis of
      calcifications in abdominal malignancies. 

PMID- 24334570
TI  - Meta-analysis of the ADH1B and ALDH2 polymorphisms and the risk of colorectal
      cancer in East Asians.
AB  - OBJECTIVE: The aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B
      (ADH1B) genes have been implicated in the development of colorectal cancer (CRC).
      However, the results are inconsistent. In this study, a meta-analysis was
      performed to assess the associations between the ALDH2 and ADH1B polymorphisms
      and the risk of CRC. METHODS: Relevant studies were identified using PubMed, Web
      of Science and CNKI up to February, 2013. The pooled odds ratio (OR) with a 95%
      confidence interval (CI) was calculated using the fixed- or random-effects model.
      RESULTS: A total of 11 case-controlled studies were selected. Of these, 11
      studies included 2,893 cases and 3,817 controls concerning the ALDH2 Glu487Lys
      polymorphism and six studies included 1,864 cases and 3,502 controls concerning
      the ADH1B polymorphism. The results indicated that there was a statistically
      significant link between the ALDH2 polymorphism and the risk of CRC
      (Glu/Lys+Lys/Lys vs. Glu/Glu: OR=0.87, 95%CI: 0.78-0.96, p=0.10; Glu/Lys vs.
      Glu/Glu: OR=0.87, 95%CI: 0.77-0.97, p=0.38); however, no significant associations
      were observed between the ADH1B polymorphism and the risk of CRC win any of the
      genetic models. CONCLUSION: This meta-analysis demonstrated that the ALDH2
      polymorphism, but not the ADH1B polymorphism, significantly increases the risk of
      CRC in East Asians.

PMID- 24334569
TI  - eIF2alpha phosphorylation bypasses premature senescence caused by oxidative
      stress and pro-oxidant antitumor therapies.
AB  - Eukaryotic cells respond to various forms of stress by blocking mRNA translation
      initiation via the phosphorylation of the alpha (alpha) subunit of eIF2 at serine
      51 (S51) (eIFalphaP). An important role of eIF2alphaP is the regulation of redox
      homeostasis and adaptation of cells to oxidative stress. Herein, we demonstrate
      that eIF2alphaP guards cells from intracellular reactive oxygen species (ROS) via
      the inhibition of senescence. Specifically, genetic inactivation of either
      eIF2alphaP or eIF2alpha kinase PERK in primary mouse or human fibroblasts leads
      to proliferative defects associated with increased DNA damage, G2/M accumulation
      and induction of premature senescence. Impaired proliferation of either PERK or
      eIF2alphaP-deficient primary cells is caused by increased ROS and restored by
      anti-oxidant treatment. Contrary to primary cells, impaired eIF2alphaP in
      immortalized mouse fibroblasts or human tumor cells provides tolerance to
      elevated intracellular ROS levels. However, eIF2alphaP-deficient human tumor
      cells are highly susceptible to extrinsic ROS generated by the pro-oxidant drug
      doxorubicin by undergoing premature senescence. Our work demonstrates that
      eIF2alphaP determines cell destiny through its capacity to control senescence in
      response to oxidative stress. Also, inhibition of eIF2alphaP may be a suitable
      means to increase the anti-tumor effects of pro-oxidant drugs through the
      induction of senescence. 

PMID- 24334571
TI  - Clinical characteristics of patients who developed hepatocellular carcinoma after
      hepatitis C virus eradication with interferon therapy: current status in Japan.
AB  - OBJECTIVE: We attempted to elucidate the clinical features of chronic hepatitis C
      patients who develop hepatocellular carcinoma (HCC) after achieving a sustained
      viral response (SVR) to interferon (IFN) therapy. METHODS: The clinical features
      of 130 patients at 19 hospitals who developed HCC after obtaining an SVR were
      retrospectively reviewed. RESULTS: Overall, 107 (82%) of the 130 patients were
      men, with 92 (71%) being >=60 years of age and 76, 38 and 16 developing HCC
      within 5, 5-10 and 10-16.9 years after IFN therapy, respectively. Before
      receiving IFN therapy, 92 (71%) patients had cirrhosis and/or a low platelet
      count (<15*10(4) cells/MUL). Lower albumin (<3.9 g/dL) and higher alpha
      fetoprotein (AFP) (>=10 ng/mL) levels were identified in a multivariate analysis
      to be independent variables of the development of HCC within five years after IFN
      therapy. Among 4,542 SVR patients, HCC occurred in 109 (2.4%) during a 5.5-year
      follow-up period, thus resulting in an occurrence rate of 4.6% for men and 0.6%
      for women. CONCLUSION: SVR patients with lower albumin or higher AFP levels
      require careful assessments to prevent early HCC development after IFN therapy.
      HCC occurrence within >10 years of IFN therapy is not uncommon, and the risk
      factors remain uncertain, thus suggesting that all SVR patients should undergo
      long-term follow-up examinations for HCC development.

PMID- 24334572
TI  - Low-density lipoprotein cholesterol is a predictor of metabolic syndrome in a
      Japanese health screening population.
AB  - OBJECTIVE: Both increased serum levels of low-density lipoprotein cholesterol
      (LDLC) and metabolic syndrome (MetS) are associated with obesity and have been
      established to be risk factors of cardiovascular disease. However, studies on the
      relationship between LDLC and MetS have been limited. METHODS: Cross-sectional
      (n=3,871) and longitudinal (n=2,558) associations between LDLC and MetS were
      examined in a Japanese health screening population. RESULTS: The odds ratio (OR)
      [95% confidence interval (CI)] of coexisting MetS for each one SD increase in the
      LDLC level was 1.25 [1.12-1.40] (p<0.001) adjusted for body mass index (BMI) and
      other confounding covariates and 1.12 [0.97-1.28] (p=0.119) adjusted for
      numerical values of the components of MetS and other confounding covariates. The
      similarly adjusted ORs [95% CIs] for the highest quartile of LDLC (Q4) compared
      with the lowest quartile (Q1) were 1.76 [1.22-2.54] (p=0.002) and 1.46 (0.93
      2.30) (p=0.101), respectively. The hazard ratio (HR) [95% CI] for developing MetS
      for each one SD increase in the LDLC level was 1.24 [1.10-1.40] (p<0.001)
      adjusted for BMI and other confounding covariates and 1.19 [1.05-1.34] (p=0.006)
      adjusted for the pre-existing dichotomous five components of MetS and other
      confounding covariates. The similarly adjusted HRs [95% CIs] for developing MetS
      for Q4 compared with Q1 were 1.71 [1.17-2.51] (p=0.006) and 1.61 [1.08-2.40]
      (p=0.020), respectively. CONCLUSION: The LDLC level is associated with coexisting
      MetS and functions as a predictor of the development of MetS, independent of BMI
      or the pre-existing components of MetS, in a Japanese health screening
      population.

PMID- 24334573
TI  - Effects of rosuvastatin vs. simvastatin/ezetimibe on arterial wall stiffness in
      patients with coronary artery disease.
AB  - OBJECTIVE: Statins prevent cardiovascular events in patients with coronary artery
      disease (CAD). However, there is little information regarding the vascular
      effects of statins on arterial wall stiffness in CAD patients. METHODS: A total
      of 36 patients were randomly assigned to receive rosuvastatin (10 mg per day) or
      simvastatin/ezetimibe (10/10 mg per day) for eight weeks. The aim of the present
      study was to determine the effects of rosuvastatin or simvastatin/ezetimibe on
      arterial wall stiffness measured according to the brachial and ankle pulse wave
      velocity (baPWV) in CAD patients. RESULTS: Both treatments significantly improved
      the levels of total cholesterol (TC), triglycerides (TGs), low-density
      lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP)
      (p<0.05). The ROCK activity and baPWV were significantly improved in the
      rosuvastatin group compared with that observed in the simvastatin/ezetimibe group
      (p<0.05). The changes in baPWV were significantly correlated with the changes in
      the ROCK activity (r=0.488, p<0.01), but not with the changes in the lipid
      profile or the hs-CRP level. CONCLUSION: Compared with simvastatin/ezetimibe
      (10/10 mg), rosuvastatin (10 mg) appears to more effectively improve arterial
      wall stiffness that may be mediated by modulation of the ROCK activity.

PMID- 24334574
TI  - Seasonal variation of severe hypoglycemia in hospitalized patients 60 years of
      age or older presenting to an emergency center hospital between 2004 and 2010.
AB  - OBJECTIVE: To investigate the seasonal variation of severe hypoglycemia in
      hospitalized elderly patients. METHODS: Among the patients hospitalized in our
      department between 2004 and 2010, we analyzed the records of 67 patients who
      required emergency admission for severe hypoglycemia and were aged 60 years or
      older. Comparisons were made between those admitted during the warm season (April
      September) and those in the cold season (October-March). PATIENTS: The mean age
      of the 67 patients was 76+/-8 years, including 45 men and 22 women. Twenty-four
      patients were admitted in the warm season and 43 patients were admitted in the
      cold season, with the average annual number being 3.4+/-1.9 and 6.1+/-2.8,
      respectively (p<0.05). RESULTS: Admissions for patients taking insulin showed no
      significant difference between the warm and cold season. In contrast,
      significantly fewer patients taking oral hypoglycemic agents were admitted in the
      warm season than in the cold season (5 vs. 22, p<0.05). Among them, 26 patients
      (96%) were taking sulfonylurea, and anorexia associated with acute infections was
      the main cause of severe hypoglycemia. In the warm season, all of the patients
      were discharged without complications, while 8 patients had complications in the
      cold season. CONCLUSION: A seasonal variation regarding hospitalization was
      observed for severe hypoglycemia among the patients 60 years of age or older,
      with a higher incidence in the cold season than the warm season, and anorexia
      related to infections in patients taking sulfonylureas was responsible for this
      variation. Accordingly, careful management of acute illness is needed for
      patients using sulfonylureas, especially during the cold season.

PMID- 24334575
TI  - Usefulness of low-dose methotrexate monotherapy for treating sarcoidosis.
AB  - OBJECTIVE: Methotrexate (MTX) is a cytotoxic agent that is commonly employed as
      an alternative to corticosteroids to treat sarcoidosis, although the proper use
      and efficacy of MTX as a single agent remain unclear. METHODS: The clinical
      records of patients newly diagnosed with sarcoidosis who were admitted to our
      institution between 2000 and 2009 were reviewed. Among these patients, 26
      received 7.5 mg of MTX per week as a single agent, and the independent effects of
      MTX were analyzed. RESULTS: Six of the 26 patients (23%) exhibited an improvement
      of sarcoidosis-related lesions. The skin lesions demonstrated a relatively higher
      response rate (37%) than the pulmonary lesions (9%). Ten of the 26 patients (39%)
      experienced adverse effects, mostly mild hepatotoxicity. No severe adverse
      effects, including irreversible hepatotoxicity, were observed. CONCLUSION:
      Although the efficacy of low-dose MTX monotherapy for sarcoidosis in this study
      was not high (23%), some patients exhibited definite improvements, and the drug
      proved to be safe, suggesting its possible benefits as a single agent for
      treating sarcoidosis.

PMID- 24334576
TI  - Investigation of antimuscarinic receptor autoantibodies in patients with acquired
      idiopathic generalized anhidrosis.
AB  - OBJECTIVE: The autoimmune mechanism is considered to play an important role in
      the development of acquired idiopathic generalized anhidrosis (AIGA), and
      muscarinic M3 receptors (M3Rs) on eccrine glands are possible autoimmune targets.
      We investigated the existence of autoantibodies against M3Rs in AIGA patients.
      METHODS: We immunostained M3R-expressing cultured cells with the serum of 12 AIGA
      patients (mean age: 35.0+/-11.7 years, mean disease duration: 26.6+/-25.8 months)
      and 10 healthy subjects (mean age: 32.4+/-10.4 years). RESULTS: The surface of
      the M3R-expressing cells was stained by the serum obtained from one of the 12
      AIGA patients but not by the serum obtained from the remaining 11 patients or
      healthy subjects. CONCLUSION: The presence of M3R autoantibodies may therefore be
      related to the underlying mechanism of disease in a subset of AIGA patients.

PMID- 24334577
TI  - Presence of fibromyalgia in patients with Takayasu's arteritis.
AB  - OBJECTIVE: Data regarding the frequency of fibromyalgia (FM) in patients with
      Takayasu's arteritis (TAK) have not been previously reported. We aimed to
      investigate the frequency of FM in TAK, defined according to the new 2010 ACR
      Preliminary Diagnostic Criteria for Fibromyalgia. The association between the ACR
      1990 and 2010 FM criteria and the effects of patient-reported outcomes (PROs) on
      FM were also analyzed. METHODS: We studied 55 patients (age: 42,30+/-12,37 years,
      F/M: 49/6) with TAK and 40 age- and sex-matched controls (age: 41+/-10.84 years,
      F/M: 31/9). All patients were examined for FM tender points by two observers and
      asked to complete the ACR 2010 FM questionnaire for FM. The SF-36, the Health
      Assessment Questionnaire (HAQ) and hospital anxiety and depression scales (HADS)
      were used to assess the quality of life. Thirty patients were reevaluated six
      months later. RESULTS: Seven (12.7%) patients with TAK and four patients with HC
      (10%) fulfilled the 2010 FM criteria (p=0.682), while three (5.4%) TAK patients
      and no controls (0%) met the 1990 criteria (p=0.133). FM was found at a
      significantly higher rate in the active patients than in the inactive patients
      according to the ACR-2010 FM criteria (p=0.006). The SF-36 physical component
      scores were significantly lower (p=0.003) and the HAQ scores were significantly
      higher in the TAK (p=0.006) patients than in the controls. CONCLUSION: The
      frequency of FM is similar between the general population and patients with TAK.
      However, the incidence of FM is significantly higher in active patients. The new
      FM criteria subscales (WPI, SSS) are significantly correlated with scales such as
      the SF-36, anxiety and depression scales and HAQ in TAK patients, suggesting
      that, in a minority of patients with FM and TAK, PROs may be affected by the
      presence of FM.

PMID- 24334578
TI  - Semipermeable membrane dressings can be used with the nicotine transdermal system
      and do not interfere with nicotine absorption.
AB  - OBJECTIVE: Adverse skin reactions as a local side effect of nicotine patches
      sometimes interfere with smoking cessation therapy. We studied the effects of
      semipermeable membrane dressings (SMD) used under nicotine patches (NP) on
      nicotine absorption, as assessed according to the urinary cotinine levels, and
      skin symptoms. METHODS: First, the urinary cotinine levels were compared in eight
      nonsmokers that applied NP over SMD and NP without SMD (Study 1). The urinary
      cotinine levels were measured using a highly sensitive competitive enzyme
      immunoassay. Second, 28 subjects undergoing NP therapy for diagnosed nicotine
      dependence were randomly assigned into two groups in a crossover design to
      receive NP over SMD and NP without SMD. The urinary cotinine levels and skin
      symptoms were compared between the two treatment groups. During the follow-up
      period of 48 weeks, the smoking cessation rate was evaluated (Study 2). RESULTS:
      No statistical differences were observed in the urinary cotinine levels between
      the NP over SMD and NP without SMD groups. In Study 2, the skin symptoms improved
      with the use of SMD in 42.8% (6/14) of the patients and worsened in 28.5% (4/14)
      of the patients. No serious skin disorders were reported. The subjects followed
      in Study 2 exhibited smoking cessation rates of 92.8%, 78.5% and 64.2% at 12, 24
      and 48 weeks, respectively. CONCLUSION: The use of NP over SMD is a safe and
      effective alternative application to NP treatment for preventing the skin
      symptoms caused by NP without interfering with nicotine absorption.

PMID- 24334579
TI  - Gastric pyogenic granuloma detected due to abdominal symptoms and treated with
      endoscopic resection.
AB  - The patient was a 35-year-old man who felt persistent hunger pain for five
      months. Upper gastrointestinal scope studies revealed a 20-mm polypoid lesion
      located in the middle body of the stomach. The pathological diagnosis revealed a
      granuloma in the biopsy specimens. The eradication of Helicobacter pylori had no
      effect on the patient's abdominal symptoms. Ultimately, the polypoid lesion was
      resected using endoscopy, and the patient was relieved of his hunger pain. The
      final diagnosis was a pyogenic granuloma in the stomach. This study is the first
      report of a pyogenic granuloma in the stomach in which the patient's abdominal
      pain disappeared after tumor resection performed via endoscopy. 

PMID- 24334580
TI  - Primary liposarcoma of the duodenum: a first case presentation.
AB  - A 55-year-old man suffering from melena was admitted to our hospital. A blood
      test showed severe anemia. Contrast-enhanced computed tomography (CT) revealed a
      huge lesion in the duodenum and dilatation of the common bile duct. Upper
      gastrointestinal endoscopy also identified hemorrhaging from the tumor in the
      duodenum. Due to the low density of the tumor mass, we performed emergency
      pylorus-preserving pancreaticoduodenectomy. Histology revealed an area of well
      differentiated liposarcoma as well as an area of high-grade spindle cells and
      pleomorphic sarcoma without obvious differentiation. The final pathological
      diagnosis was dedifferentiated liposarcoma. This is the first case report of
      primary liposarcoma of the duodenum. 

PMID- 24334581
TI  - Cardiac arrest in a patient with polyarteritis nodosa.
AB  - Polyarteritis nodosa (PAN) is a rare necrotizing vasculitis that occurs in small-
      to medium-sized muscular arteries. A 71-year-old man was admitted to our hospital
      for an evaluation of a sustained fever and he later died of cardiac arrest. The
      autopsy revealed that the patient had PAN and severe coronary vasculitis with no
      signs of cardiac ischemia. The reason for the patient's sudden death remains
      unclear; however, cardiac arrest due to coronary vasculitis was suggested. This
      is a rare case of PAN coronary vasculitis that led to sudden death without either
      stenosis or any embolism. 

PMID- 24334582
TI  - A successful case of percutaneous transluminal septal myocardial ablation for
      mitral regurgitation that emerged following mitral valve repair surgery.
AB  - A 70-year-old man complaining of exertional dyspnea was referred to our hospital
      for recurrence of mitral regurgitation (MR) after mitral valve repair.
      Echocardiography revealed the presence of a bulging subaortic septum with flow
      acceleration in the left ventricular outflow tract (LVOT) and systolic anterior
      motion of the mitral valve with moderate MR, consistent with LVOT obstruction.
      Since medical therapy was not sufficiently effective, we performed percutaneous
      transluminal septal myocardial ablation (PTSMA). After the procedure, the MR
      resolved, with a reduced LVOT pressure gradient. The patient's symptoms improved.
      PTSMA was effective for the treatment of MR that emerged after mitral valve
      repair. 

PMID- 24334583
TI  - Rapid progression of neuromuscular disorder related cardiomyopathy in a young
      patient.
AB  - An 11-year and 3-month-old boy with a neuromuscular disorder was admitted for
      dyspnea. Echocardiography revealed severe left ventricular dysfunction with an
      ejection fraction (EF) of 17%. However, the EF had been 57% when the patient was
      10 years and 9 months old. The patient's clinical condition became refractory,
      and he died on the 155th day of hospitalization. Speckle-tracking analysis was
      retrospectively performed, which demonstrated that the global radial strain was
      within the normal range; however, the global longitudinal and circumferential
      strains were lower -than -normal 10 years and 9 months of age. Adult
      neuromuscular disorder-related secondary cardiomyopathy generally progresses
      slowly, although progression depends on the age of onset of cardiomyopathy. 

PMID- 24334584
TI  - Evaluation of insulin secretion and sensitivity in a patient with slowly
      progressive type 1 diabetes mellitus.
AB  - We herein report the case of a patient with slowly progressive type 1 diabetes
      and insulin independence lasting for >10 years despite the detection of
      continuously elevated glutamic acid decarboxylase autoantibody titers. We
      monitored the patient's clinical course and analyzed his endogenous insulin
      secretion and sensitivity using an intravenous glucose tolerance test (IVGTT) and
      oral glucose tolerance test (OGTT). His body mass index remained at approximately
      22, while his serum C-peptide immunoreactivity level gradually decreased. The
      level of insulin secretion was significantly higher on the OGTT than the IVGTT.
      The patient's insulin sensitivity was within the normal limits. These results
      suggest that maintaining a lifestyle sufficient to preserve insulin secretion
      and/or normal insulin sensitivity is important and that beta-cell responsiveness
      to incretins may, in part, contribute to insulin independence. 

PMID- 24334585
TI  - A favorable response to cisplatin, pemetrexed and bevacizumab in two cases of
      invasive mucinous adenocarcinoma formerly known as pneumonic-type mucinous
      bronchioloalveolar carcinoma.
AB  - The leading subtype of lung cancer, adenocarcinoma, received a new classification
      in 2011 when multifocal, pneumonic-type mucinous tumors, formerly called mucinous
      bronchioloalveolar carcinomas, were reclassified as "invasive mucinous
      adenocarcinomas." These tumors appear to be less sensitive to chemotherapy than
      other non-small cell lung cancers. We herein report two cases of invasive
      mucinous adenocarcinoma that showed a dramatic radiologic response to combination
      therapy with cisplatin, pemetrexed and bevacizumab. Recent data suggest that the
      use of paclitaxel-based chemotherapy is an acceptable therapeutic strategy in
      cases of invasive mucinous adenocarcinoma. The cases reported here and
      preclinical findings suggest the therapeutic efficacy of cisplatin, pemetrexed
      and bevacizumab in treating such tumors. 

PMID- 24334586
TI  - Papillary squamous cell carcinoma of the trachea associated with human
      papillomavirus-18 infection.
AB  - A 75-year-old man presented with the chief complaints of coughing and dyspnea.
      Chest computed tomography revealed narrowing of the trachea. A tumor measuring
      40*33*15 mm in size that caused -90% reduction in the cross-sectional area of the
      trachea 4 cm above the carina was cauterized with high-frequency electrocautery
      via a rigid bronchoscope. A pathological examination revealed papillary squamous
      cell carcinoma with immunohistochemical p16 overexpression. Multiplex polymerase
      chain reaction confirmed human papillomavirus type 18 DNA in the tumor. At the 12
      month follow-up visit following the administration of radiotherapy, the patient
      exhibited no local recurrence or distant metastasis. 

PMID- 24334587
TI  - Two cases of acute respiratory distress syndrome with high values of
      Chlamydophila pneumoniae-specific antibodies.
AB  - We herein report two cases of acute respiratory distress syndrome (ARDS) with
      high values of Chlamydophila pneumoniae-specific antibodies. In the first case (a
      65-year-old man), high levels of anti-C. pneumoniae antibodies (IgG and IgA) were
      detected on admission, and the anti-C. pneumoniae IgA level rose by Day 30. The
      patient was successfully treated with quinolone and steroids. In the second case
      (an 85-year-old man), abnormally high levels of anti-C. pneumoniae IgM were
      detected on admission. The patient did not recover, despite receiving treatment
      with several antibiotics and anti-inflammatory agents. Neither of the patients
      displayed other pathogen-specific antigens or antibodies. Chlamydophila pneumonia
      is usually mild, although it can cause severe interstitial pneumonia and ARDS in
      reinfected patients and the elderly. 

PMID- 24334588
TI  - A patient who survived primary seasonal influenza viral pneumonia: histologic
      findings obtained via bronchoscopy.
AB  - The histological findings and clinical course of primary seasonal influenza viral
      pneumonia have not been fully elucidated. We herein report the case of a 65-year
      old man with primary seasonal influenza viral pneumonia. The patient presented
      with fever, myalgia, general fatigue and dyspnea of seven days duration. Chest
      computed tomography showed bilateral ground-glass opacity and consolidation. A
      rapid influenza virus antigen test was positive for influenza A virus. We
      diagnosed him as having community-acquired influenza pneumonia and started
      therapy with antibiotics plus oseltamivir; however, his symptoms, respiratory
      condition and radiological findings deteriorated. Polymerase chain reaction
      following bronchoscopy showed the bronchoalveolar lavage fluid to be positive for
      the influenza A virus. A right lower lobe transbronchial lung biopsy revealed
      type II pneumocyte metaplasia, acute and chronic interstitial infiltrates and
      alveolar organization without hyaline membranes or fibrin thrombi in the vascular
      lumen. Treatment with prednisolone at a dose of 60 mg/day (1 mg/kg) resulted in
      an improvement. The patient was discharged on hospital day 15. Two weeks after
      admission, the serum antibody titer for influenza A (H3N2) had increased
      significantly. No other pathogens were found either serologically or in the
      respiratory samples, and we diagnosed the patient to therefore have primary
      influenza viral pneumonia. 

PMID- 24334589
TI  - Extramedullary hematopoietic pleural effusion accompanied by follicular lymphoma.
AB  - Extramedullary hematopoietic effusion (EHE) is recognized to be an unusual
      phenomenon accompanied by hematologic disorders. Only a few reports are available
      of EHE occurring in patients with lymphoma. We herein report the case of a 54
      year-old man with follicular lymphoma. Bone marrow aspirates and biopsied
      specimens showed diffuse invasion of small cleaved atypical lymphoid cells that
      were positive for CD10, 20, bcl2, immunoglobulin lambda and Bcl-2-IgH
      rearrangement. The pleural effusion aspirates and a biopsied specimen obtained
      via thoracoscopy revealed megakaryocytes and immature myeloid cells in addition
      to lymphoma cells. To the best of our knowledge, this is the first report of EHE
      accompanied by lymphoma according to the World Health Organization
      classification. 

PMID- 24334590
TI  - Successful treatment of histiocytic sarcoma and concurrent HIV infection using a
      combination of CHOP and antiretroviral therapy.
AB  - Histiocytic sarcoma (HS) is a rare malignancy of soft tissues with an unknown
      etiology. The CHOP (cyclophosphamide, vincristine sulfate, doxorubicin
      hydrochloride and prednisolone) regimen is often adopted as first-line
      chemotherapy; however, its therapeutic efficacy against HS is usually low. We
      herein first present the case of a patient with HS who was infected with human
      immunodeficiency virus-1 (HIV) in whom treatment with a combination of CHOP and
      antiretroviral therapy (ART) was successful. The patient has been in complete
      remission for 12 months following the discontinuation of chemotherapy under
      continuous ART. This case report may help to promote further investigation of
      both HS and HIV-related malignancy. 

PMID- 24334591
TI  - Ophthalmoplegia and flaccid paraplegia in a patient with anti-NMDA receptor
      encephalitis: a case report and literature review.
AB  - We herein report the case of a 26-year-old woman with anti-N-methyl-D-aspartate
      receptor (NMDAR) encephalitis presenting with ophthalmoplegia and flaccid
      paraplegia. She developed disorientation and hallucination after fever and
      vomiting. Hypothermia, hypoventilation, hypertension, paralytic ileus and
      hyponatremia were present. Neurological examination showed mild consciousness
      disturbance and bilateral ophthalmoplegia on admission, flaccid paraplegia with
      leg areflexia on Day 4. Anti-NMDAR antibodies were detected in the serum and
      cerebrospinal fluid samples. Motor nerve conduction velocity was decreased in the
      tibial and peroneal nerves. F-wave amplitudes were reduced in the tibial nerve.
      MRI disclosed lesions in the callosal splenium, hippocampus and cerebral
      subarachnoid regions. In addition to various encephalitic symptoms, physicians
      should pay more attention to peripheral nerve damage in patients with anti-NMDAR
      encephalitis. 

PMID- 24334592
TI  - A hemorrhagic pineal cyst with a bacterial meningitis-like manifestation and
      benign outcome.
AB  - Pineal cysts are a common incidental finding in imaging studies, and the majority
      of such cysts are asymptomatic. However, hemorrhaging pineal cysts, which are
      considered to be rare, are often associated with severe symptoms. We herein
      describe the case of a 58-year-old patient with the novel manifestation of a
      bleeding pineal cyst, who had a benign outcome without any surgical treatment.
      Although the clinical manifestations resembled those of bacterial meningitis,
      magnetic resonance images suggested chemical meningitis caused by an intracystic
      hemorrhage and rupture of the pineal cyst. 

PMID- 24334593
TI  - Progression of bilateral internal carotid artery dissection during antiplatelet
      therapy.
AB  - Bilateral internal carotid artery dissection (ICAD) is a rare but important cause
      of stroke in young adults. Anticoagulant and/or antiplatelet agents are usually
      recommended for stroke prevention;however, such treatments remain highly
      controversial, and there are inadequate data to compare the efficacy of
      anticoagulation and antiplatelet therapy. We herein report the case of 30-year
      old man presenting with progressive bilateral ICAD during antiplatelet treatment.
      This report suggests the possibility that intramural hematomas are enlarged by
      antiplatelet and anticoagulant agents and draws attention to the medications
      associated with ICAD. 

PMID- 24334594
TI  - A Japanese case of vertebral sarcoidosis.
AB  - We herein report the first Japanese case of vertebral sarcoidosis diagnosed using
      multiple imaging modalities and a biopsy. CT, MRI and (18)F-fluorodeoxyglucose
      positron emission tomography (18F-FDG PET) detected multiple vertebral lesions,
      and a vertebral biopsy guided by the PET findings confirmed the diagnosis of
      vertebral sarcoidosis. Although the disease was refractory to corticosteroids,
      treatment with methotrexate (MTX) achieved a good response. Our case suggests
      that MRI and 18F-FDG PET are useful for determining the site for a biopsy and
      that MTX is effective for treating vertebral sarcoidosis. 

PMID- 24334595
TI  - Spur cell anemia associated with alcoholic cirrhosis.

PMID- 24334596
TI  - Yellow nail syndrome.

PMID- 24334597
TI  - Pneumatosis intestinalis in a patient with myasthenia gravis.

PMID- 24334598
TI  - Radiographic features of rhupus arthropathy.

PMID- 24334599
TI  - Segmental zoster paresis of the right shoulder.

PMID- 24334600
TI  - Herpes zoster duplex bilateralis.

PMID- 24334601
TI  - Experimental verification of ion stopping power prediction from dual energy CT
      data in tissue surrogates.
AB  - We present an experimental verification of stopping-power-ratio (SPR) prediction
      from dual energy CT (DECT) with potential use for dose planning in proton and ion
      therapy. The approach is based on DECT images converted to electron density
      relative to water rhoe/rhoe, w and effective atomic number Zeff. To establish a
      parameterization of the I-value by Zeff, 71 tabulated tissue compositions were
      used. For the experimental assessment of the method we scanned 20 materials
      (tissue surrogates, polymers, aluminum, titanium) at 80/140Sn kVp and 100/140Sn
      kVp (Sn: additional tin filtration) and computed the rhoe/rhoe, w and Zeff with a
      purely image based algorithm. Thereby, we found that rhoe/rhoe, w (Zeff) could be
      determined with an accuracy of 0.4% (1.7%) for the tissue surrogates with known
      elemental compositions. SPRs were predicted from DECT images for all 20 materials
      using the presented approach and were compared to measured water-equivalent path
      lengths (closely related to SPR). For the tissue surrogates the presented DECT
      approach was found to predict the experimental values within 0.6%, for aluminum
      and titanium within an accuracy of 1.7% and 9.4% (from 16-bit reconstructed DECT
      images). 

PMID- 24334602
TI  - Trapeziectomy and ligament reconstruction tendon interposition for isolated
      scaphotrapeziotrapezoid osteoarthritis of the wrist.
AB  - Isolated osteoarthritis of the scaphotrapeziotrapezoid joint is rather rare
      compared with thumb trapeziometacarpal osteoarthritis. The aim of this
      retrospective study was to evaluate the outcome of 15 consecutive patients
      treated with trapeziectomy/ligament reconstruction tendon interposition for
      isolated scaphotrapeziotrapezoid osteoarthritis of the wrist. After a mean follow
      up of 54 months, 14 patients (15 wrists) were available for clinical and
      radiological examination. The median pain intensity was 0 on a 0-10 visual
      analogue scale, both at rest and with activity, mean grip strength averaged 24
      kg, pinch strength 5 kg. The disabilities of the arm, shoulder and hand (DASH)
      score was 16, and a modified Mayo Wrist Score 84. Correlation between the degree
      of scaphotrapezoid osteoarthritis and pain at rest, pain with activity, and DASH
      score was not significant. The findings from our study suggest that
      trapeziectomy/ligament reconstruction tendon interposition is an effective
      procedure for treating isolated scaphotrapeziotrapezoid osteoarthritis, and that
      additional partial trapezoid excision is not necessary. 

PMID- 24334603
TI  - Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia
      cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl
      downregulation.
AB  - PURPOSE: Chronic myelogenous leukemia (CML) is characterized by the constitutive
      activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation
      that causes resistance to imatinib, cytotoxic drugs, and the second-generation
      tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with
      CML leads to searching for novel approaches to the treatment of CML. Gambogic
      acid, a small molecule derived from Chinese herb gamboges, has been approved for
      phase II clinical trial for cancer therapy by the Chinese Food and Drug
      Administration (FDA). In this study, we investigated the effect of gambogic acid
      on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr
      Abl. EXPERIMENTAL DESIGN: CML cell lines (KBM5, KBM5-T315I, and K562), primary
      cells from patients with CML with clinical resistance to imatinib, and normal
      monocytes from healthy volunteers were treated with gambogic acid, imatinib, or
      their combination, followed by measuring the effects on cell growth, apoptosis,
      and signal pathways. The in vivo antitumor activity of gambogic acid and its
      combination with imatinib was also assessed with nude xenografts. RESULTS:
      Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells
      and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude
      mice. Our data suggest that GA-induced proteasome inhibition is required for
      caspase activation in both imatinib-resistant and -sensitive CML cells, and
      caspase activation is required for gambogic acid-induced Bcr-Abl downregulation
      and apoptotic cell death. CONCLUSIONS: These findings suggest an alternative
      strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with
      the medicinal compound gambogic acid, which may have great clinical significance
      in imatinib-resistant cancer therapy.

PMID- 24334605
TI  - Smoke-related DNA methylation changes in the etiology of human disease.
AB  - Exposure to environmental and lifestyle factors, such as cigarette smoking,
      affect the epigenome and might mediate risk for diseases and cancers. We have
      performed a genome-wide DNA methylation study to determine the effect of smoke
      and snuff (smokeless tobacco) on DNA methylation. A total of 95 sites were
      differentially methylated [false discovery rate (FDR) q-values < 0.05] in smokers
      and a subset of the differentially methylated loci were also differentially
      expressed in smokers. We found no sites, neither any biological functions nor
      molecular processes enriched for smoke-less tobacco-related differential DNA
      methylation. This suggests that methylation changes are not caused by the basic
      components of the tobacco but from its burnt products. Instead, we see a clear
      enrichment (FDR q-value < 0.05) for genes, including CPOX, CDKN1A and PTK2,
      involved in response to arsenic-containing substance, which agrees with smoke
      containing small amounts of arsenic. A large number of biological functions and
      molecular processes with links to disease conditions are also enriched (FDR q
      value < 0.05) for smoke-related DNA methylation changes. These include 'insulin
      receptor binding', and 'negative regulation of glucose import' which are
      associated with diabetes, 'positive regulation of interleukin-6-mediated
      signaling pathway', 'regulation of T-helper 2 cell differentiation', 'positive
      regulation of interleukin-13 production' which are associated with the immune
      system and 'sertoli cell fate commitment' which is important for male fertility.
      Since type 2 diabetes, repressed immune system and infertility have previously
      been associated with smoking, our results suggest that this might be mediated by
      DNA methylation changes. 

PMID- 24334604
TI  - Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap
      syndrome in humans and mice.
AB  - Collagen VI-related myopathies are disorders of connective tissue presenting with
      an overlap phenotype combining clinical involvement from the muscle and from the
      connective tissue. Not all patients displaying related overlap phenotypes between
      muscle and connective tissue have mutations in collagen VI. Here, we report a
      homozygous recessive loss of function mutation and a de novo dominant mutation in
      collagen XII (COL12A1) as underlying a novel overlap syndrome involving muscle
      and connective tissue. Two siblings homozygous for a loss of function mutation
      showed widespread joint hyperlaxity combined with weakness precluding independent
      ambulation, while the patient with the de novo missense mutation was more mildly
      affected, showing improvement including the acquisition of walking. A mouse model
      with inactivation of the Col12a1 gene showed decreased grip strength, a delay in
      fiber-type transition and a deficiency in passive force generation while the
      muscle seems more resistant to eccentric contraction induced force drop,
      indicating a role for a matrix-based passive force-transducing elastic element in
      the generation of the weakness. This new muscle connective tissue overlap
      syndrome expands on the emerging importance of the muscle extracellular matrix in
      the pathogenesis of muscle disease. 

PMID- 24334607
TI  - Live cell imaging and biophotonic methods reveal two types of mutant huntingtin
      inclusions.
AB  - Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder
      that can be characterized by the presence of protein inclusions containing mutant
      huntingtin within a subset of neurons in the brain. Since their discovery, the
      relevance of inclusions to disease pathology has been controversial. We show
      using super-resolution fluorescence imaging and Forster resonance energy transfer
      (FRET) in live cells, that mutant huntingtin fragments can form two
      morphologically and conformationally distinct inclusion types. Using fluorescence
      recovery after photobleaching (FRAP), we demonstrate that the two huntingtin
      inclusion types have unique dynamic properties. The ability to form one or the
      other type of inclusion can be influenced by the phosphorylation state of serine
      residues at amino acid positions 13 and 16 within the huntingtin protein. We can
      define two types of inclusions: fibrillar, which are tightly packed, do not
      exchange protein with the soluble phase, and result from phospho-modification at
      serines 13 and 16 of the N17 domain, and globular, which are loosely packed, can
      readily exchange with the soluble phase, and are not phosphorylated in N17. We
      hypothesize that the protective effect of N17 phosphorylation or phospho-mimicry
      seen in animal models, at the level of protein inclusions with elevated
      huntingtin levels, is to induce a conformation of the huntingtin amino-terminus
      that causes fragments to form tightly packed inclusions that do not exit the
      insoluble phase, and hence exert less toxicity. The identification of these sub
      types of huntingtin inclusions could allow for drug discovery to promote
      protective inclusions of mutant huntingtin protein in HD. 

PMID- 24334606
TI  - Fine mapping of the celiac disease-associated LPP locus reveals a potential
      functional variant.
AB  - Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen
      (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease
      with a worldwide frequency of ~1%. The most significant non-HLA signal mapped to
      the intronic region of 70 kb in the LPP gene. Our aim was to fine map and
      identify possible functional variants in the LPP locus. We performed a meta
      analysis in a cohort of 25 169 individuals from six different populations
      previously genotyped using Immunochip. Imputation using data from the Genome of
      the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed
      the strong association signal on the LPP locus (rs2030519, P = 1.79 * 10(-49)),
      without any novel associations. The conditional analysis on this top SNP
      indicated association to a single common haplotype. By performing haplotype
      analyses in each population separately, as well as in a combined group of the
      four populations that reach the significant threshold after correction (P <
      0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 *
      10(-44)). By intersecting regulatory data from the ENCODE project, we found a
      functional SNP, rs4686484 (P = 3.12 * 10(-49)), that maps to several B-cell
      enhancer elements and a highly conserved region. This SNP was also predicted to
      change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and
      Nkx2.9, suggesting its role in transcriptional regulation. We later found
      significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus
      our results suggest that rs4686484 is the functional variant in this locus, while
      LPP expression is decreased in CeD. 

PMID- 24334608
TI  - Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in cochlear
      hair cells and causes hearing loss in mice.
AB  - Usher syndrome type 2 (USH2) is the predominant form of USH, a leading genetic
      cause of combined deafness and blindness. PDZD7, a paralog of two USH causative
      genes, USH1C and USH2D (WHRN), was recently reported to be implicated in USH2 and
      non-syndromic deafness. It encodes a protein with multiple PDZ domains. To
      understand the biological function of PDZD7 and the pathogenic mechanism caused
      by PDZD7 mutations, we generated and thoroughly characterized a Pdzd7 knockout
      mouse model. The Pdzd7 knockout mice exhibit congenital profound deafness, as
      assessed by auditory brainstem response, distortion product otoacoustic emission
      and cochlear microphonics tests, and normal vestibular function, as assessed by
      their behaviors. Lack of PDZD7 leads to the disorganization of stereocilia
      bundles and a reduction in mechanotransduction currents and sensitivity in
      cochlear outer hair cells. At the molecular level, PDZD7 determines the
      localization of the USH2 protein complex, composed of USH2A, GPR98 and WHRN, to
      ankle links in developing cochlear hair cells, likely through its direct
      interactions with these three proteins. The localization of PDZD7 to the ankle
      links of cochlear hair bundles also relies on USH2 proteins. In photoreceptors of
      Pdzd7 knockout mice, the three USH2 proteins largely remain unchanged at the
      periciliary membrane complex. The electroretinogram responses of both rod and
      cone photoreceptors are normal in knockout mice at 1 month of age. Therefore,
      although the organization of the USH2 complex appears different in
      photoreceptors, it is clear that PDZD7 plays an essential role in organizing the
      USH2 complex at ankle links in developing cochlear hair cells. GenBank accession
      numbers: KF041446, KF041447, KF041448, KF041449, KF041450, KF041451. 

PMID- 24334609
TI  - CLYBL is a polymorphic human enzyme with malate synthase and beta-methylmalate
      synthase activity.
AB  - CLYBL is a human mitochondrial enzyme of unknown function that is found in
      multiple eukaryotic taxa and conserved to bacteria. The protein is expressed in
      the mitochondria of all mammalian organs, with highest expression in brown fat
      and kidney. Approximately 5% of all humans harbor a premature stop polymorphism
      in CLYBL that has been associated with reduced levels of circulating vitamin B12.
      Using comparative genomics, we now show that CLYBL is strongly co-expressed with
      and co-evolved specifically with other components of the mitochondrial B12
      pathway. We confirm that the premature stop polymorphism in CLYBL leads to a loss
      of protein expression. To elucidate the molecular function of CLYBL, we used
      comparative operon analysis, structural modeling and enzyme kinetics. We report
      that CLYBL encodes a malate/beta-methylmalate synthase, converting glyoxylate and
      acetyl-CoA to malate, or glyoxylate and propionyl-CoA to beta-methylmalate.
      Malate synthases are best known for their established role in the glyoxylate
      shunt of plants and lower organisms and are traditionally described as not
      occurring in humans. The broader role of a malate/beta-methylmalate synthase in
      human physiology and its mechanistic link to vitamin B12 metabolism remain
      unknown. 

PMID- 24334611
TI  - Enzymatic and histopathologic biomarkers in the flatfish Euryglossa orientalis
      from the northwestern Persian Gulf.
AB  - Most of the chemicals in the petrochemical sewages cause oxidative stress in
      marine organisms. Antioxidant enzymes (catalase (CAT) and superoxide dismutase
      (SOD)) as biomarkers of oxidative stress and liver histopathological alterations
      were investigated in the current study to evaluate the toxic effects of
      petrochemical pollutions in flatfish, Euryglossa orientalis The enzymatic and
      histopathological changes were assessed in the liver of E. orientalis from Khowr
      e Jafari (one of the creeks from Khowr-e Musa estuary) and Sajafi harbor as
      polluted and clean areas, respectively. A significant increase in the antioxidant
      enzyme activities was observed in response to aquatic pollutions of Khowr-e
      Jafari. Liver lesions were diagnosed and categorized using standard methods. The
      results of histopathological examinations showed more lesion scores in the fish
      from Khowr-e Jafari. Various histopathological changes including hepatocyte
      degeneration, inflammatory lesions, peliosis hepatis and pancreatic acinar cell
      adenoma, and increase in the number of pigmented macrophage aggregates were
      observed in the fish from polluted site. It is suggested that activities of CAT
      and SOD along with semi-quantitative histopathologic analysis of E. orientalis
      can be used for biomonitoring programs in Persian Gulf. 

PMID- 24334610
TI  - Compromised paraspeckle formation as a pathogenic factor in FUSopathies.
AB  - Paraspeckles are nuclear bodies formed by a set of specialized proteins assembled
      on the long non-coding RNA NEAT1; they have a role in nuclear retention of
      hyperedited transcripts and are associated with response to cellular stress.
      Fused in sarcoma (FUS) protein, linked to a number of neurodegenerative
      disorders, is an essential paraspeckle component. We have shown that its
      recruitment to these nuclear structures is mediated by the N-terminal region and
      requires prion-like activity. FUS interacts with p54nrb/NONO, a major constituent
      of paraspeckles, in an RNA-dependent manner and responds in the same way as other
      paraspeckle proteins to alterations in cellular homeostasis such as changes in
      transcription rates or levels of protein methylation. FUS also regulates NEAT1
      levels and paraspeckle formation in cultured cells, and FUS deficiency leads to
      loss of paraspeckles. Pathological gain-of-function FUS mutations might be
      expected to affect paraspeckle function in human diseases because mislocalized
      amyotrophic lateral sclerosis (ALS)-linked FUS variants sequester other
      paraspeckle proteins into aggregates formed in cultured cells and into neuronal
      inclusions in a transgenic mouse model of FUSopathy. Furthermore, we detected
      abundant p54nrb/NONO-positive inclusions in motor neurons of patients with
      familial forms of ALS caused by FUS mutations, but not in other ALS cases. Our
      results suggest that both loss and gain of FUS function can trigger disruption of
      paraspeckle assembly, which may impair protective responses in neurons and
      thereby contribute to the pathogenesis of FUSopathies. 

PMID- 24334612
TI  - Determining molecular predictors of adverse drug reactions with causality
      analysis based on structure learning.
AB  - OBJECTIVE: Adverse drug reaction (ADR) can have dire consequences. However, our
      current understanding of the causes of drug-induced toxicity is still limited.
      Hence it is of paramount importance to determine molecular factors of adverse
      drug responses so that safer therapies can be designed. METHODS: We propose a
      causality analysis model based on structure learning (CASTLE) for identifying
      factors that contribute significantly to ADRs from an integration of chemical and
      biological properties of drugs. This study aims to address two major limitations
      of the existing ADR prediction studies. First, ADR prediction is mostly performed
      by assessing the correlations between the input features and ADRs, and the
      identified associations may not indicate causal relations. Second, most
      predictive models lack biological interpretability. RESULTS: CASTLE was evaluated
      in terms of prediction accuracy on 12 organ-specific ADRs using 830 approved
      drugs. The prediction was carried out by first extracting causal features with
      structure learning and then applying them to a support vector machine (SVM) for
      classification. Through rigorous experimental analyses, we observed significant
      increases in both macro and micro F1 scores compared with the traditional SVM
      classifier, from 0.88 to 0.89 and 0.74 to 0.81, respectively. Most importantly,
      identified links between the biological factors and organ-specific drug
      toxicities were partially supported by evidence in Online Mendelian Inheritance
      in Man. CONCLUSIONS: The proposed CASTLE model not only performed better in
      prediction than the baseline SVM but also produced more interpretable results
      (ie, biological factors responsible for ADRs), which is critical to discovering
      molecular activators of ADRs.

PMID- 24334613
TI  - Age-associated stresses induce an anti-inflammatory senescent phenotype in
      endothelial cells.
AB  - Age is the greatest risk factor for cardiovascular disease. In addition,
      inflammation and age (senescence) have been linked at both the clinical and
      molecular levels. In general, senescent cells have been described as pro
      inflammatory based on their senescence associated secretory phenotype (SASP).
      However, we have previously shown that senescence induced by overexpression
      ofSENEX (or ARHGAP18), in endothelial cells results in an anti-inflammatory
      phenotype. We have investigated, at the individual cellular level, the senescent
      phenotype of endothelial cells following three of the chief signals associated
      with ageing; oxidative stress, disturbed flow and hypoxia. All three stimuli
      induce senescence and, based on neutrophil adhesion and expression of the
      adhesion molecules E-selectin and VCAM-1, a population of senescent cells is seen
      that is resistant to inflammatory stimuli and thus we define as anti
      inflammatory. The proportion of anti-inflammatory cells increases with time but
      remains stable at approximately 50% by eight days after induction of senescence,
      suggesting that these are stable phenotypes of endothelial cell senescence.
      Similar to other senescent cell types, p38MAPK blockade inhibits the development
      of the pro-inflammatory phenotype but unique to EC, there is a corresponding
      increase in the number of anti-inflammatory senescent cells. Thus stress-induced
      senescent endothelial cells display a mosaic of inflammatory phenotypes. The anti
      inflammatory population suggests that senescent endothelial cells may have an
      unique protective role, to inhibit uncontrolled proliferation and to limit the
      local inflammatory response. 

PMID- 24334614
TI  - Role of DNA damage in cardiovascular disease.
AB  - Patients with some progeroid syndromes, such as Werner syndrome, exhibit
      atherosclerotic cardiovascular disease (CVD) at a young age as a manifestation of
      premature aging. Recent studies have revealed that most progeroid syndromes are
      caused by genetic defects in specific molecules involved in the DNA damage
      response, a cornerstone of genome stability. Ionizing radiation is one of the
      most potent genotoxic stimuli and causes various kinds of DNA damage. Further,
      there is increasing evidence that therapeutic radiation treatments can cause
      cardiovascular complications. Here, we describe the DNA damage and subsequent
      response, review recent advances in the understanding of the molecular basis of
      progeroid syndromes (especially those syndromes that involve CVD), review the
      pathological and epidemiological analysis of radiation-induced CVD, and discuss
      the possible role of DNA damage and the DNA damage response in the pathogenesis
      of atherosclerotic CVD.

PMID- 24334616
TI  - Incomplete avulsion fractures of the scapular spine caused by violent muscle
      contraction.
AB  - Two percent of scapular fractures occur as a result of indirect trauma caused by
      traction of the muscles and ligaments attached to the scapula. We present two
      cases involving adults with incomplete avulsion fractures of the scapular spine
      caused by violent voluntary contraction of the deltoid muscle. These cases are
      the first reported avulsion fractures confined to the scapular spine medial to
      the spinoglenoid notch. Although the fractures were incomplete, one patient had a
      typical symptom of scapular fracture - pseudo-rupture of the rotator cuff
      characterized by clinical signs of a complete rupture of the musculotendinous
      cuff. Although this symptom is generally thought to be caused by massive
      hemorrhaging under the rotator-cuff muscle bellies, it may develop from modest
      bleeding through the formation of an intramuscular hematoma and a resultant
      elevation in intramuscular pressure. Confirming the presence of tenderness on the
      scapular spine and performing appropriate imaging investigation constitute a
      clinically effective method for preventing misdiagnosis. 

PMID- 24334615
TI  - Myocardial matrix-polyethylene glycol hybrid hydrogels for tissue engineering.
AB  - Similar to other protein-based hydrogels, extracellular matrix (ECM) based
      hydrogels, derived from decellularized tissues, have a narrow range of mechanical
      properties and are rapidly degraded. These hydrogels contain natural cellular
      adhesion sites, form nanofibrous networks similar to native ECM, and are
      biodegradable. In this study, we expand the properties of these types of
      materials by incorporating poly(ethylene glycol) (PEG) into the ECM network. We
      use decellularized myocardial matrix as an example of a tissue specific ECM
      derived hydrogel. Myocardial matrix-PEG hybrids were synthesized by two different
      methods, cross-linking the proteins with an amine-reactive PEG-star and photo
      induced radical polymerization of two different multi-armed PEG-acrylates. We
      show that both methods allow for conjugation of PEG to the myocardial matrix by
      gel electrophoresis and infrared spectroscopy. Scanning electron microscopy
      demonstrated that the hybrid materials still contain a nanofibrous network
      similar to unmodified myocardial matrix and that the fiber diameter is changed by
      the method of PEG incorporation and PEG molecular weight. PEG conjugation also
      decreased the rate of enzymatic degradation in vitro, and increased material
      stiffness. Hybrids synthesized with amine-reactive PEG had gelation rates of 30
      min, similar to the unmodified myocardial matrix, and incorporation of PEG did
      not prevent cell adhesion and migration through the hydrogels, thus offering the
      possibility to have an injectable ECM hydrogel that degrades more slowly in vivo.
      The photo-polymerized radical systems gelled in 4 min upon irradiation, allowing
      3D encapsulation and culture of cells, unlike the soft unmodified myocardial
      matrix. This work demonstrates that PEG incorporation into ECM-based hydrogels
      can expand material properties, thereby opening up new possibilities for in vitro
      and in vivo applications.

PMID- 24334617
TI  - Legius syndrome, an Update. Molecular pathology of mutations in SPRED1.
AB  - Multiple cafe-au-lait macules (CALMs) are the hallmark of Von Recklinghausen
      disease, or neurofibromatosis type 1 (NF1). In 2007 we reported that some
      individuals with multiple CALMs have a heterozygous mutation in the SPRED1 gene
      and have NF1-like syndrome, or Legius syndrome. Individuals with Legius syndrome
      have multiple CALMs with or without freckling, but they do not show the typical
      NF1-associated tumors such as neurofibromas or optic pathway gliomas. NF1
      associated bone abnormalities and Lisch nodules are also not reported in patients
      with Legius syndrome. Consequently, individuals with Legius syndrome require less
      intense medical surveillance than those with NF1. The SPRED1 gene was identified
      in 2001 and codes for a protein that downregulates the RAS-mitogen activated
      protein kinase (RAS-MAPK) pathway; as does neurofibromin, the protein encoded by
      the NF1 gene. It is estimated that about 1-4% of individuals with multiple CALMs
      have a heterozygous SPRED1 mutation. Mutational and clinical data on 209 patients
      with Legius syndrome are tabulated in an online database
      (http://www.lovd.nl/SPRED1). Mice with homozygous knockout of the Spred1 gene
      show learning deficits and decreased synaptic plasticity in hippocampal neurons
      similar to those seen in Nf1 heterozygous mice, underlining the importance of the
      RAS-MAPK pathway for learning and memory. Recently, specific binding between
      neurofibromin and SPRED1 was demonstrated. SPRED1 seems to play an important role
      in recruiting neurofibromin to the plasma membrane. 

PMID- 24334618
TI  - The adaptive FEM elastic model for medical image registration.
AB  - This paper proposes an adaptive mesh refinement strategy for the finite element
      method (FEM) based elastic registration model. The signature matrix for mesh
      refinement takes into account the regional intensity variance and the local
      deformation displacement. The regional intensity variance reflects detailed
      information for improving registration accuracy and the deformation displacement
      fine-tunes the mesh refinement for a more efficient algorithm. The gradient flows
      of two different similarity metrics, the sum of the squared difference and the
      spatially encoded mutual information for the mono-modal and multi-modal
      registrations, are used to derive external forces to drive the model to the
      equilibrium state. We compared our approach to three other models: (1) the
      conventional multi-resolution FEM registration algorithm; (2) the FEM elastic
      method that uses variation information for mesh refinement; and (3) the robust
      block matching based registration. Comparisons among different methods in a
      dataset with 20 CT image pairs upon artificial deformation demonstrate that our
      registration method achieved significant improvement in accuracies. Experimental
      results in another dataset of 40 real medical image pairs for both mono-modal and
      multi-modal registrations also show that our model outperforms the other three
      models in its accuracy. 

PMID- 24334619
TI  - Compassion conundrums.

PMID- 24334621
TI  - Observation of localized strains on vertically grown single-walled carbon
      nanotube forests via polarized Raman spectroscopy.
AB  - Vertically grown single-walled carbon nanotube (V-SWCNT) forests, synthesized by
      water-assisted plasma-enhanced chemical vapor deposition, were studied using
      polarized micro-Raman spectroscopy. Among three different sections (root, center
      and end) along the vertical growth direction, the degree of V-SWCNT alignment was
      highest in the center section. Raman frequency red-shifts up to 7 and 13 cm(-1),
      for RBM and G-band, respectively, were observed in the center section, with
      respect to the Raman frequencies measured in the root and the end sections. Raman
      frequency downshift and concurrent linewidth broadening of the G-band, revealing
      a localized strain, were also observed in the center section. The existence of a
      localized strain in the center section of the V-SWCNT was further confirmed by
      observing a strong polarization anisotropy of up to 8 cm(-1) in the G-band Raman
      frequency for different polarized Raman scattering configurations at the same
      probed spot. 

PMID- 24334623
TI  - A high pressure x-ray photoelectron spectroscopy study of CO oxidation over
      Rh(100).
AB  - We have studied the oxidation of CO over Rh(100) using high pressure x-ray
      photoelectron spectroscopy under CO and O2 pressures ranging from 0.01 to 1 mbar.
      The results show a very low or no conversion for the CO covered surface found at
      low temperatures, while the activity rises slightly when the temperature is high
      enough for some CO to desorb, exposing surface sites for dissociative O2
      adsorption. As the temperature is increased further, more CO desorbs and oxygen
      replaces CO as the dominating species at the surface. At the same time we find a
      sudden increase in the reactivity, such that all CO that reaches the surface is
      instantly transformed into CO2. We find that the O coverage in the active state
      is highly dependent on the total pressure and, although we do not detect any
      presence of a surface oxide as in previous surface x-ray diffraction studies, the
      highest O coverage indicates that the surface is close to being oxidized. 

PMID- 24334622
TI  - Metagenomic frameworks for monitoring antibiotic resistance in aquatic
      environments.
AB  - BACKGROUND: High-throughput genomic technologies offer new approaches for
      environmental health monitoring, including metagenomic surveillance of antibiotic
      resistance determinants (ARDs). Although natural environments serve as reservoirs
      for antibiotic resistance genes that can be transferred to pathogenic and human
      commensal bacteria, monitoring of these determinants has been infrequent and
      incomplete. Furthermore, surveillance efforts have not been integrated into
      public health decision making. OBJECTIVES: We used a metagenomic epidemiology
      based approach to develop an ARD index that quantifies antibiotic resistance
      potential, and we analyzed this index for common modal patterns across
      environmental samples. We also explored how metagenomic data such as this index
      could be conceptually framed within an early risk management context. METHODS: We
      analyzed 25 published data sets from shotgun pyrosequencing projects. The samples
      consisted of microbial community DNA collected from marine and freshwater
      environments across a gradient of human impact. We used principal component
      analysis to identify index patterns across samples. RESULTS: We observed
      significant differences in the overall index and index subcategory levels when
      comparing ecosystems more proximal versus distal to human impact. The selection
      of different sequence similarity thresholds strongly influenced the index
      measurements. Unique index subcategory modes distinguished the different
      metagenomes. CONCLUSIONS: Broad-scale screening of ARD potential using this index
      revealed utility for framing environmental health monitoring and surveillance.
      This approach holds promise as a screening tool for establishing baseline ARD
      levels that can be used to inform and prioritize decision making regarding
      management of ARD sources and human exposure routes. CITATION: Port JA, Cullen
      AC, Wallace JC, Smith MN, Faustman EM. 2014. Metagenomic frameworks for
      monitoring antibiotic resistance in aquatic environments. Environ Health Perspect
      122:222-228; http://dx.doi.org/10.1289/ehp.1307009

PMID- 24334624
TI  - Organic solar cells using CVD-grown graphene electrodes.
AB  - We report on the development of flexible organic solar cells (OSCs) incorporating
      graphene sheets synthesized by chemical vapor deposition (CVD) as transparent
      conducting electrodes on polyethylene terephthalate (PET) substrates. A key
      barrier that must be overcome for the successful fabrication of OSCs with
      graphene electrodes is the poor-film properties of water-based poly(3,4
      ethylenedioxythiphene):poly(styrenesulfonate) (PEDOT:PSS) when coated onto
      hydrophobic graphene surfaces. To form a uniform PEDOT:PSS film on a graphene
      surface, we added perfluorinated ionomers (PFI) to pristine PEDOT:PSS to create
      'GraHEL', which we then successfully spin coated onto the graphene surface. We
      systematically investigated the effect of number of layers in layer-by-layer
      stacked graphene anode of an OSC on the performance parameters including the open
      circuit voltage (Voc), short-circuit current (Jsc), and fill factor (FF). As the
      number of graphene layers increased, the FF tended to increase owing to lower
      sheet resistance, while Jsc tended to decrease owing to the lower light
      absorption. In light of this trade-off between sheet resistance and
      transmittance, we determined that three-layer graphene (3LG) represents the best
      configuration for obtaining the optimal power conversion efficiency (PCE) in OSC
      anodes, even at suboptimal sheet resistances. We finally developed efficient,
      flexible OSCs with a PCE of 4.33%, which is the highest efficiency attained so
      far by an OSC with CVD-grown graphene electrodes to the best of our knowledge.

PMID- 24334625
TI  - Trends in percentage of postgraduate dental trainees at dental clinics.
AB  - A facilities-group system designed to provide clinical training at dental clinics
      was developed after postgraduate clinical training became mandatory for dentists
      in Japan in 2006. As a result, there has been a steady increase in the number of
      dental clinics collaborating with dental school hospitals under this program. A
      larger number of dental clinics have also been designated as single-system
      facilities, program management facilities or collaborating facilities. However,
      it remains to be determined whether this increase in the number of dental clinics
      designated as clinical training facilities has led to an increase in the amount
      of training offered. Therefore, the purpose of this study was to investigate
      trends in the percentage of postgraduate dental trainees at dental clinics
      between fiscal years 2006 and 2010. The results showed no significant correlation
      among (1) the percentage of dental clinics designated as single-system
      collaborating facilities, (2) the percentage of training programs at dental
      clinics, and (3) the proportion of training program recruitment offers by dental
      clinics compared to the total number of recruits. These findings showed that
      increasing the number of collaborating dental clinics did not lead to an increase
      in the amount of clinical training at dental clinics. The findings also suggest
      that increasing the number of single-system or program management dental clinics
      is important in promoting clinical training at dental clinics. 

PMID- 24334626
TI  - EQCM analysis of titanium corrosion in peroxide- or fluoride-containing
      solutions.
AB  - Although offering superior resistance to corrosion, titanium is unable to
      withstand discoloration with exposure to peroxide or fluoride. The mechanism of
      this discoloration, however, remains to be clarified. The purpose of this study
      was to investigate the mechanism underlying discoloration of titanium with
      immersion in peroxide- or fluoride-containing solutions based on electrochemical
      quartz crystal microbalance (EQCM) analysis. A 9-MHz titanium-deposited quartz
      crystal was used as for the electrodes. Four test solutions were prepared for
      immersion of the electrodes: 154 mM (0.9%) NaCl; 150 mM H2O2+154 mM NaCl (pH=4 by
      addition of lactic acid); 150 mM H2O2+154 mM NaCl (pH=8 by addition of sodium
      hydroxide solution); and 48 mM (0.2%) NaF+154 mM NaCl (pH=5.0 by addition of
      lactic acid). A WinEchem electrochemistry software-controlled quartz crystal
      analyzer (QCA922) and the Potentiostat/Galvanostat (Princeton Applied Research)
      on Windows XP were used to measure concurrently the resonance frequency and
      potential of the electrodes. The EQCM data differed among solutions. In the
      acidulated fluoride-containing solution, the electrode showed lower open circuit
      potential and a gradual increase in electrode frequency, indicating a loss of
      mass by titanium dissolution. In the peroxide-containing solution, although open
      circuit potential showed no marked difference, electrode frequency showed a
      gentle decrease in acidic solution, indicating a gain in mass by oxidation; but
      an increase in alkaline solution, indicating a loss of mass by dissolution. These
      results confirmed that exposure to acidulated fluoride- or alkaline peroxide
      containing solutions causes dissolution-induced discoloration, while that to
      acidulated peroxide-containing solutions resulted in the formation of an oxide
      film together with discoloration.

PMID- 24334627
TI  - Does mandatory postgraduate clinical training worsen geographic distribution of
      dentists in Japan?
AB  - Postgraduate clinical training for dentists has been mandatory in Japan since
      2006. Hirata et al. reported that the geographic distribution of postgraduate
      dental trainees by prefecture in 2006 was worse than that of practicing dentists.
      This suggests that the postgraduate clinical training system could intensify the
      problem of distribution of dentists. In this study, therefore, we reviewed the
      geographic distribution of postgraduate dental trainees and practicing dentists
      between 2006 and 2010 in detail by city, ward, town and village by using the
      Lorenz curve and Gini coefficient. The results showed that while there was no
      significant worsening of geographic distribution of postgraduate dental trainees,
      the distribution of practicing dentists continued to deteriorate. A number of
      reasons may explain these findings: the clinical training system is based on a
      one-year employment contract, and dentists subsequently relocate as driven by the
      market; and geographic distribution among cities, towns and villages has worsened
      as a result of the merger of municipalities. The geographic distribution of
      practicing dentists is expected to deteriorate further if the number of dentists
      takes a downward turn in the future. Therefore, it is necessary to continuously
      review the distribution of postgraduate dental trainees. 

PMID- 24334628
TI  - Effect of framework design on fracture resistance in zirconia 4-unit all-ceramic
      fixed partial dentures.
AB  - The purpose of this study was to conduct static load-bearing tests on 4-unit Y
      TZP all-ceramic fixed partial denture (FPD) frameworks with different cross
      sectional areas and forms to evaluate the influence of connector design on
      fracture load. Each of the central, mesial and distal connectors was prepared
      with one of 2 different cross-sectional areas and one of 3 different forms (one
      circular and two oval forms) to give a total of 18 designs. Five frameworks were
      then prepared for each design, making a total of 90. Each framework was cemented
      to the test model with glass ionomer cement. Fracture load was measured with a
      universal testing machine at a cross-head speed of 1.0 mm/min. A three-way ANOVA
      revealed significant differences in fracture load depending on cross-sectional
      area, central connector cross-sectional form, or mesial/distal connector cross
      sectional form (p<0.01). No interaction was observed, however, between any two
      connector design elements. The results of a Tukey analysis revealed a significant
      difference between the two connector cross-sectional areas investigated, with an
      increase in connector cross-sectional area resulting in an increase in fracture
      load. Fracture load decreased as the height of the mesial or distal connector
      decreased. Fracture load was significantly higher in frameworks in which the
      height of the central connector was greater than that of the distal or mesial
      connector. In conclusion, these results suggest that sufficient height needs to
      be maintained in the mesial/distal connector to secure a high fracture load in
      zirconia 4-unit all-ceramic FPDs. Moreover, even when this is not possible, a
      high fracture load may still be obtained by making the height of the central
      connector as great as possible. Furthermore, extending the connector cross
      sectional area is effective in increasing fracture load. 

PMID- 24334629
TI  - Occlusal treatment with bite splint improves dyskinesia in Parkinson's disease
      patient: a case report.
AB  - The patient was a 46-year-old woman requesting oral hygiene control. She had been
      treated for Parkinson's disease at the neurology department of another university
      hospital for 9 years. When the drugs were effective (drug efficacy), she could
      get out of bed and change clothes without assistance, albeit slowly. When the
      drugs were ineffective (no drug efficacy), however, she found it difficult to get
      out of bed, change clothes, or maintain posture during defecation without
      assistance. Occlusion was B-1 on the Eichner index, and neither dislocation of
      the temporomandibular joint nor mandibular tremor was observed. At her first
      visit, a medical history was taken and periodontal therapy commenced. Informed
      consent for bite splint therapy was obtained after examination of movement
      disorder. A bite splint was made for her, and any change in the grade of motor
      disorder using the bite splint evaluated. In addition, her grip strength was
      measured when wearing and not wearing the bite splint during periods of drug
      efficacy and no drug efficacy. The patient could get out of bed, change clothes,
      and maintain posture during defecation without assistance when wearing the bite
      splint, even during no drug efficacy. Grip strength in her left hand during drug
      efficacy and in both hands during no drug efficacy was greater when wearing the
      bite splint than without the bite splint. When this patient with Parkinson's
      disease wore a bite splint, her athletic ability and grip strength increased. 

PMID- 24334630
TI  - Schwannoma derived from lingual nerve occurring in floor of mouth.
AB  - A schwannoma is a benign tumor composed of schwann cells which forms on the
      periphery of nerves. We report a case of a schwannoma derived from a lingual
      nerve occurring in the floor of the mouth. The patient was a 27-year-old woman
      who presented with the complaint of a swelling in the floor of the mouth. It is
      difficult to distinguish a swelling from a sublingual gland tumor, cyst, or
      malignant tumor by MRI alone. Therefore, a biopsy and cytological examination
      were performed one week prior to surgery to determine whether the growth
      represented a malignancy. The results revealed a class II growth which was
      suspected to be a schwannoma. Intraoperatively, it became clear that the tumor
      and lingual nerve were inseparable, making excision of the nerve unavoidable. On
      the other hand, there was a clear border between the tumor and the sublingual
      gland, so it was possible to preserve the sublingual gland. In the postoperative
      pathological diagnosis, a definitive diagnosis was difficult based solely on H-E
      staining. Therefore, immunohistochemical staining was performed, resulting in a
      diagnosis of schwannoma. Currently, the patient is still being followed up. The
      results of this case indicate that preoperative aspiration biopsy cytology is
      useful in deciding the operative method to be employed. 

PMID- 24334631
TI  - Effect of combination of trigger point injection and stellate ganglion block on
      non-odontogenic mandibular molar pain referred from masseter muscle: a case
      report.
AB  - We report a case of myofascial pain syndrome (MPS), manifested as nonodontogenic
      mandibular molar pain referred from the masseter muscle, relieved by a
      combination of trigger point injection (TPI) and stellate ganglion block (SGB).
      The patient was a 32-year-old woman who had experienced cold hypersensitivity in
      the right third mandibular molar 2 months prior to visiting our department.
      Subsequently, she had visited a family dentist and undergone pulpectomy under
      local anesthesia. She eventually visited our clinic because there was no marked
      change in her symptoms. On the first visit, no tooth abnormality was found and
      the patient was neither anxious nor depressive. Tender points were found in the
      right masseter and temporal muscles during muscle palpation. Referred pain
      radiating to the right mandibular molars was observed when pressure was applied
      to the central portion of the right masseter muscle. As a result, we diagnosed
      MPS based on evidence of nonodontogenic tooth pain caused by referred pain from
      the masseter muscle. We performed TPI with 2% lidocaine hydrochloride to the
      tender point in the masseter muscle. Although the visual analog scale (VAS) pain
      score dropped from 97 to 36, complete pain relief was not achieved. The TPI was
      effective for approximately 7 hrs, after which severe throbbing pain returned.
      The sustained nature of the tooth pain suggested that it was sympathetic nerve
      dependent. Subsequently, we performed SGB, resulting in a reduction in the VAS
      pain score from 90 to 32. Therefore, we performed another TPI and the VAS pain
      score dropped to 0. We continued SGB and TPI for the next 3 days and the symptoms
      disappeared. Thus, a combination of TPI and SGB controlled MPS manifested as
      masseter muscle-mediated nonodontogenic tooth pain. 

PMID- 24334632
TI  - Analysis of dental treatment performed by dental residents at General Dentistry
      Department of Tokyo Dental College Chiba Hospital over 6 years following
      introduction of mandatory dental clinical training system.
AB  - Six years have passed since the introduction of legislation mandating at least 1
      year of clinical training for those who have passed the national dentist
      examination. To determine whether clinical training has been appropriately
      implemented at the General Dentistry Department of Tokyo Dental College Chiba
      Hospital, a managed-type clinical training facility, the number of patients
      treated and types of dental and dental technical work performed by dental
      residents trained by the department were summarized and analyzed. The number of
      patients treated per dental resident increased from 11 in 2006 to 15 in 2011. By
      treatment type, periodontic treatment was the most frequently performed
      throughout the study period, followed by endodontic treatment. Conservation
      treatment, prosthodontic treatment with crowns/bridges, and prosthodontic
      treatment with dentures were performed at a similar moderate frequency, while
      oral surgical treatment was performed least frequently throughout the study
      period. The frequency of periodontic treatment increased slightly, whereas that
      of endodontic treatment decreased slightly or remained almost unchanged after
      introduction of the mandatory clinical training system. When the distribution of
      dental treatment performed at our department was compared with that of dental
      treatment performed by general dentists across Japan in 2011, our department
      showed a slightly lower frequency of periodontic treatment and higher frequency
      of endodontic treatment than the national total, whereas the frequency of other
      types of treatment was similar between the two populations. These results
      demonstrated that appropriate clinical training has been provided by our
      department to meet the purpose of offering dentists the opportunity to acquire
      the basic diagnostic and treatment abilities that would enable them to provide
      appropriate treatment for injuries and diseases frequently encountered in daily
      practice. The study also revealed some problems, such as a decreasing number of
      residents engaging in dental technical work each year. For additional improvement
      in the quality of dental clinical training, more analyses are needed to further
      identify and address potential problems in the system. 

PMID- 24334633
TI  - Recent trends among dental residents at Tokyo Dental College.
AB  - Trends among dental residents at Tokyo Dental College between 2006, at which time
      clinical residency became mandatory, and 2011 were analyzed and the following
      results obtained. Almost all the eligible students from our school participated
      in the orientation seminar on dental residency programs. Although the number
      varied slightly by year, approximately 70 to 150 students from other schools also
      participated in these orientation seminars. Almost all the students from our
      school and 60 to 80% of those from other schools participating in the orientation
      seminar each year applied to sit the dental residency entrance examination. The
      number of candidates was highest in 2006 (318) and lowest in 2010 (205) (average:
      248), and the applicant-to-seat ratio for residency was 1.59. The examination
      pass rate was 59.02%. Approximately 10% of the students from other schools were
      admitted as dental residents. 

PMID- 24334634
TI  - Small animal fluorescence and bioluminescence tomography: a review of approaches,
      algorithms and technology update.
AB  - Emerging fluorescence and bioluminescence tomography approaches have several
      common, yet several distinct features from established emission tomographies of
      PET and SPECT. Although both nuclear and optical imaging modalities involve
      counting of photons, nuclear imaging techniques collect the emitted high energy
      (100-511 keV) photons after radioactive decay of radionuclides while optical
      techniques count low-energy (1.5-4.1 eV) photons that are scattered and absorbed
      by tissues requiring models of light transport for quantitative image
      reconstruction. Fluorescence imaging has been recently translated into clinic
      demonstrating high sensitivity, modest tissue penetration depth, and fast,
      millisecond image acquisition times. As a consequence, the promise of
      quantitative optical tomography as a complement of small animal PET and SPECT
      remains high. In this review, we summarize the different instrumentation,
      methodological approaches and schema for inverse image reconstructions for
      optical tomography, including luminescence and fluorescence modalities, and
      comment on limitations and key technological advances needed for further
      discovery research and translation. 

PMID- 24334635
TI  - Functional metagenomic profiling of intestinal microbiome in extreme ageing.
AB  - Age-related alterations in human gut microbiota composition have been thoroughly
      described, but a detailed functional description of the intestinal bacterial
      coding capacity is still missing. In order to elucidate the contribution of the
      gut metagenome to the complex mosaic of human longevity, we applied shotgun
      sequencing to total fecal bacterial DNA in a selection of samples belonging to a
      well-characterized human ageing cohort. The age-related trajectory of the human
      gut microbiome was characterized by loss of genes for shortchain fatty acid
      production and an overall decrease in the saccharolytic potential, while
      proteolytic functions were more abundant than in the intestinal metagenome of
      younger adults. This altered functional profile was associated with a relevant
      enrichment in "pathobionts", i.e. opportunistic pro-inflammatory bacteria
      generally present in the adult gut ecosystem in low numbers. Finally, as a
      signature for long life we identified 116 microbial genes that significantly
      correlated with ageing. Collectively, our data emphasize the relationship between
      intestinal bacteria and human metabolism, by detailing the modifications in the
      gut microbiota as a consequence of and/or promoter of the physiological changes
      occurring in the human host upon ageing. 

PMID- 24334636
TI  - Prosthetic valve thrombosis caused by heparin-induced thrombocytopenia thrombosis
      during pregnancy.

PMID- 24334637
TI  - High normal urine albumin-to-creatinine ratio predicts development of
      hypertension in Korean men.
AB  - BACKGROUND: Microalbuminuria is known as a risk factor for hypertension. Recently
      it was suggested that urine albumin-to-creatinine ratio (UACR), even within the
      normal range, can be associated with hypertension, but the temporal relationship
      between normal range UACR and hypertension was not confirmed. Therefore the aim
      of this study was to verify an association between normal range UACR and the
      development of hypertension in Korean men. METHODS AND RESULTS: This prospective
      cohort study was performed on 1,284 initially non-hypertensive Korean men. The
      total follow-up period was 4,109.5 person-years and the mean follow-up period was
      3.2+/-1.51 years. Cox proportional hazards model was used to estimate the hazard
      ratios (HR) for the risk of hypertension development. After adjusting for
      multiple covariates, the HR (95% confidence interval [CI]) for incident
      hypertension, comparing the second to the fourth quartiles of UACR level to the
      first quartile, were 1.35 (95% CI: 0.93-1.97), 1.55 (95% CI: 1.07-2.25) and 1.89
      (95% CI: 1.31-2.71), respectively (P for trend=0.001). CONCLUSIONS: High UACR
      within the normal range was significantly associated with hypertension
      development. Furthermore, this association remained significant after adjusting
      for multiple baseline covariates. 

PMID- 24334638
TI  - Production of reactive oxygen species in the diabetic heart. Roles of
      mitochondria and NADPH oxidase.
AB  - Reactive oxygen species (ROS) are the main facilitators of cardiovascular
      complications in diabetes mellitus (DM), and the ROS level is increased in
      cultured cells exposed to high glucose concentrations or in diabetic animal
      models. Emerging evidence shows that mitochondria and nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase are dominant mechanisms of ROS production
      in the diabetic heart. Hyperpolarization of the mitochondrial inner membrane
      potentials and impaired mitochondrial function promote ROS production in the
      mitochondria of the diabetic heart. Uncoupling proteins are upregulated and may
      reduce the ROS level by depolarizing the mitochondrial inner membrane potential.
      NADPH oxidase is another major site of ROS production and its contribution to DM
      induced ROS increase has been elucidated not only in vascular smooth muscle cells
      and endothelial cells, but also in cardiomyocytes. Protein kinase C, angiotensin
      II, and advanced glycation endproducts (AGEs)/receptor for AGEs can activate
      NADPH oxidase. Increased intracellular calcium level mediated via the Na(+)-H(+)
      exchanger and subsequent activation of Ca(2+)/calmodulin-dependent protein kinase
      II may also activate NADPH oxidase. This review presents the current
      understanding of the mechanisms of ROS production, focusing especially on the
      roles of mitochondria and NADPH oxidase. 

PMID- 24334639
TI  - Report of the American Heart Association (AHA) Scientific Sessions 2013, Dallas.
AB  - The American Heart Association (AHA) Scientific Sessions were held in Dallas on
      November 16-20, 2013. The meeting is one of the most leading conferences of
      cardiology in the world, with over 18,000 professional attendees from more than
      105 countries. There were 315 invited sessions and 443 abstract sessions,
      comprising more than 5,000 presentations. The sessions were expanded to 26
      program tracks, which included and integrated basic, translational, clinical, and
      population science. In the series of late-breaking sessions, updates of results
      from 20 clinical trials were disclosed. Japanese scientists submitted the second
      most abstracts to the Scientific Sessions in 2013. We appreciate the significant
      contribution to the sessions by Japanese cardiologists as well as the Japanese
      Circulation Society.

PMID- 24334640
TI  - One year after mild injury: comparison of health status and quality of life
      between patients with whiplash versus other injuries.
AB  - OBJECTIVE: To compare health status, effect on family, occupational consequences,
      and quality of life (QOL) 1 year after an accident between patients with whiplash
      versus other mild injuries, and to explore the relationship between initial
      injury (whiplash vs other) and QOL. METHODS: This was a prospective cohort study.
      The study used data from the ESPARR cohort (a representative cohort of road
      accident victims) and included 173 individuals with "pure" whiplash and 207 with
      other mild injuries. QOL at 1-year followup was assessed on the World Health
      Organization Quality of Life questionnaire. Correlations between explanatory
      variables and QOL were explored by Poisson regression to provide adjusted
      relative risks, with ANOVA for the various QOL scores explored. RESULTS: One year
      post-accident, more patients who had whiplash than other casualties complained of
      nonrecovery of health status (56% vs 43%) and of the occupational effect of pain
      (31% vs 23%). QOL and posttraumatic stress disorder (PTSD) were similar in the 2
      groups. Impaired QOL did not correlate with whiplash when models were adjusted on
      sociodemographic variables and history of psychological distress. Whatever the
      initial lesion, PTSD was a determining factor for poorer QOL. CONCLUSION:
      Sociodemographic factors, preaccident psychological history prior to the
      accident, and PTSD were the main factors influencing QOL, rather than whether the
      injury was whiplash. PTSD may also be related to pain.

PMID- 24334641
TI  - A longterm prospective real-life experience with leflunomide in juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To describe a clinical practice with leflunomide (LEF) in juvenile
      idiopathic arthritis (JIA). METHODS: Patients with JIA seen between May 2008 and
      May 2012 and considered nonresponsive to methotrexate (MTX) were given LEF and
      prospectively followed. Primary outcome was a 28-joint Disease Activity Score
      (DAS28) of low disease activity (< 3.2) in less than 6 months. Childhood Health
      Assessment Questionnaire (CHAQ) scores and safety data were recorded. RESULTS:
      Forty-three patients (33 female) were included with 25 (58.1%) polyarticular, 10
      oligoarticular (7 extended; 3 persistent), 6 systemic, and 2 enthesitis-related.
      Ten (23.2%) were rheumatoid factor-positive and 7 (16.3%) had antinuclear
      antibodies. Prior drugs other than MTX: 11 (25.5%) chloroquine diphosphate + MTX
      and 2 (4.6%) sulfasalazine + MTX; mean prednisone dose was 6.4 +/- 9.3 mg. The
      MTX dose prior to LEF was 14.5 +/- 4.5 mg/m(2)/week. LEF dose and duration of
      therapy were 16.6 +/- 5.2 mg/d and 3.6 +/- 2.2 years, respectively. Nineteen
      patients (44.2%) interrupted LEF: 1 entered remission, 11 were nonresponsive, and
      7 were intolerant (16.2%). Baseline DAS28 (5.57 +/- 0.7) dropped to 3.7 +/- 1.2
      at final analysis (p < 0.001) and 16 patients (37.2%) had a low DAS28 [< 3.2; 12
      (27.9%) while taking LEF + MTX and 4 (9.3%) while taking monotherapy]. At last
      followup, the number of patients with DAS28 > 5.1 dropped from 34 (79%) to 9
      (20.9%) and CHAQ scores from 0.86 +/- 0.7 to 0.44 +/- 0.5 (p < 0.001).
      CONCLUSION: LEF isolated or combined with MTX is effective and safe to treat JIA
      in patients refractory to MTX.

PMID- 24334642
TI  - Health literacy predicts discrepancies between traditional written patient
      assessments and verbally administered assessments in rheumatoid arthritis.
AB  - OBJECTIVE: Patient assessments of disease activity (PtGA) and general health (GH)
      measured by visual analog scale (VAS) are widely used in rheumatoid arthritis
      (RA) clinical practice and research. These require comprehension of the
      question's wording and translation of disease activity onto a written VAS, which
      is problematic for patients with limited health literacy (HL) or difficulty
      completing forms. This study's objective was to validate verbally administered
      versions of patient assessments and identify factors that might explain
      discrepancies between verbal and written measures. METHODS: We enrolled patients
      with RA at the Denver Health rheumatology clinic (n = 300). Subjects were
      randomized to complete the traditional written PtGA and GH and one of the verbal
      assessments. Subjects provided a verbal numeric response after reading the
      question, having the question read to them in person, or hearing the question
      over the phone. Spearman and Lin correlations comparing written and verbal
      assessments were determined. Multivariate logistic regression was performed to
      explain any discrepancies. RESULTS: The instruments administered verbally in
      person showed good, but not excellent, correlation with traditional written VAS
      forms (Spearman coefficients 0.59 to 0.70; p < 0.001 for all correlations).
      Twenty-three percent of subjects were unable to complete 1 of the written VAS
      assessments without assistance. HL predicted missing written data and
      discrepancies between verbal and written assessments (p < 0.05 for all
      correlations). CONCLUSION: Providers should use verbal versions of PtGA and GH
      with caution while caring for patients unable to complete traditional written
      version. Limited HL is widely prevalent and a barrier to obtaining patient
      oriented data.

PMID- 24334643
TI  - Flares in rheumatoid arthritis: frequency and management. A report from the BRASS
      registry.
AB  - OBJECTIVE: To describe the frequency, duration, and management of flares as
      reported by patients with rheumatoid arthritis (RA). METHODS: Data were collected
      in a prospective observational study of patients with RA recruited from a single
      academic center and treated according to the rheumatologists' discretion. Every 6
      months, patients reported the number and duration of RA flares and described how
      these were managed in terms of adding or changing medication and use of
      nonpharmacologic strategies. RESULTS: Of patients who reported flares at least
      once during the study, 74% reported having flares 6 months prior to study entry
      and 59% reported flares prior to the first 6-month visit. At subsequent visits,
      54-57% reported having > 1 flare. Thirty percent of patients in remission
      reported flares. Flare duration lasted >= 2 weeks in 30%, 1-2 weeks in 13%, and <
      1 week in 57%. Forty percent reported medication changes at the time of their
      flare; 16% changed medication and used nonpharmacologic strategies and 26% of
      patients reported no changes in treatment as a result of flares. Longer duration
      of flare was associated with changes in disease-modifying therapy. CONCLUSION:
      Patients with RA experienced flares more often when noted to be in higher disease
      activity states than when in remission and reported changes in disease-modifying
      antirheumatic drugs or biologics more frequently when flares were of longer
      duration. There is a need to prospectively study symptom intensity and duration
      of flare in relation to disease activity and consider self-management strategies
      in the development of a measure of flare.

PMID- 24334644
TI  - A clinical, pathological, and genetic characterization of methotrexate-associated
      lymphoproliferative disorders.
AB  - OBJECTIVE: Methotrexate-associated lymphoproliferative disorders (MTX-LPD) often
      regress spontaneously during MTX withdrawal, but the prognostic factors remain
      unclear. The aim of our study was to clarify the clinical, histological, and
      genetic factors that predict outcomes in patients with MTX-LPD. METHODS: Patients
      with MTX-LPD diagnosed between 2000 and 2012 were analyzed retrospectively
      regarding their clinical course, site of biopsy, histological typing, Epstein
      Barr virus (EBV) in situ hybridization and immunostaining, and HLA type. RESULTS:
      Twenty-one patients, including 20 with rheumatoid arthritis (RA) and 1 with
      polymyositis, were analyzed. The mean dose of MTX was 6.1 mg/week and the mean
      duration of treatment was 71.1 months. Clinically, 5 patients were diagnosed with
      EBV-positive mucocutaneous ulcer (EBVMCU) and had polymorphic histological
      findings. The proportion of those patients successfully treated solely by
      withdrawal of MTX was significantly greater than that of those without EBVMCU
      (75% vs 7.7%, p = 0.015). The HLA-B15:11 haplotype was more frequent in patients
      with EBV+ RA with MTX-LPD than in healthy Japanese controls (p = 0.0079,
      Bonferroni's method). EBV latency classification and HLA typing were not
      associated with the prognosis of MTX-LPD in our cohort. CONCLUSION: Our data
      demonstrate that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD,
      had a better clinical outcome when MTX was withdrawn than did other patients with
      MTX-LPD.

PMID- 24334645
TI  - Evidence for genetic association of CARD9 and SNAPC4 with ankylosing spondylitis
      in a Chinese Han population.
AB  - OBJECTIVE: A genome-wide association study and 2 replication studies identified 2
      single-nucleotide polymorphisms (SNP) of caspase recruitment domain-containing
      protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4)
      at Chr 9q34.3 associated with ankylosing spondylitis (AS) in whites. We explored
      a possible association of SNP in CARD9 and SNAPC4 and AS in a Chinese Han
      population from Shandong. METHODS: The study included 1150 patients with AS and
      1120 healthy controls who underwent genotyping for 4 SNP of CARD9 and 2 of
      SNAPC4; we replicated the results in another 490 patients and 380 healthy
      controls of Ningxia Han Chinese during the same time. We used quantitative real
      time PCR (qRT-PCR) to measure CARD9 and SNAPC4 mRNA expression in peripheral
      leukocytes from 44 patients and 36 controls and allele-specific mRNA expression
      of CARD9 and SNAPC4 in leukocytes from 130 controls. RESULTS: We validated that
      an SNP in SNAPC4, rs11145835, was significantly associated with AS in our Chinese
      Han population (p = 0.001) and replicated the association in samples from the
      Chinese Ningxia Han population (p = 0.002). Carrying the G allele of rs11145835
      was associated with increased risk of AS (OR 1.34, 95% CI 1.12-1.59) and with
      decreased expression of CARD9 (p = 0.001) and SNAPC4 (p = 0.02) in leukocytes.
      SNAPC4 mRNA expression was lower in leukocytes from patients than from controls
      (p = 0.0002). CONCLUSION: Our study confirmed that an SNP rs11145835 in 9q34.3
      that harbors CARD9 and SNAPC4 is associated with AS in a Chinese Han population,
      and rs11145835 in SNAPC4 is a potential causal variant.

PMID- 24334646
TI  - Deregulated NLRP3 and NLRP1 inflammasomes and their correlations with disease
      activity in systemic lupus erythematosus.
AB  - OBJECTIVE: NOD-like receptor family, pyrin domain containing 3 and 1 (NLRP3 and
      NLRP1) inflammasomes are molecular platforms that sense the damage or danger
      signals of cells. We investigated whether NLRP3/NLRP1 inflammasomes are involved
      in the pathogenesis and progression of systemic lupus erythematosus (SLE).
      METHODS: Expressions of inflammasome components at the mRNA and protein levels in
      the peripheral blood mononuclear cells (PBMC) from patients with SLE and healthy
      controls were investigated by quantitative real-time transcription PCR and
      Western blot, respectively. Correlations between NLRP3/NLRP1 inflammasome
      components' expression and clinical disease progression were investigated.
      Expressions of NLRP3/NLRP1 inflammasomes before and after treatment in the
      patients with SLE were also analyzed and compared. RESULTS: Our data showed that
      expressions of NLRP3/NLRP1 inflammasomes were significantly downregulated in PBMC
      from patients with SLE compared with PBMC from healthy controls. Further,
      expressions of NLRP3/NLRP1 inflammasomes were negatively correlated with the SLE
      Disease Activity Index, and regular glucocorticoid treatment significantly
      corrected this deregulation of these inflammasomes. Further analysis showed that
      type I interferon (IFN) level was significantly negatively correlated with
      expression of NLRP3/NLRP1 inflammasomes, which indicated that enhanced IFN-I
      level in patients with SLE was responsible, at least to a great degree, for the
      deregulation of inflammasomes. CONCLUSION: These results indicated deregulation
      of NLRP3/NLRP1 inflammasomes in patients with SLE, and suggested an important
      role for inflammasomes in the pathogenesis and progression of SLE.

PMID- 24334647
TI  - Determining a magnetic resonance imaging inflammatory activity acceptable state
      without subsequent radiographic progression in rheumatoid arthritis: results from
      a followup MRI study of 254 patients in clinical remission or low disease
      activity.
AB  - OBJECTIVE: To assess the predictive value of magnetic resonance imaging (MRI)
      detected subclinical inflammation for subsequent radiographic progression in a
      longitudinal study of patients with rheumatoid arthritis (RA) in clinical
      remission or low disease activity (LDA), and to determine cutoffs for an MRI
      inflammatory activity acceptable state in RA in which radiographic progression
      rarely occurs. METHODS: Patients with RA in clinical remission [28-joint Disease
      Activity Score-C-reactive protein (DAS28-CRP) < 2.6, n = 185] or LDA state (2.6
      <= DAS28-CRP < 3.2, n = 69) with longitudinal MRI and radiographic data were
      included from 5 cohorts (4 international centers). MRI were assessed according to
      the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS).
      Statistical analyses included an underlying conditional logistic regression model
      stratified per cohort, with radiographic progression as dependent variable.
      RESULTS: A total of 254 patients were included in the multivariate analyses. At
      baseline, synovitis was observed in 95% and osteitis in 49% of patients.
      Radiographic progression was observed in 60 patients (24%). RAMRIS synovitis was
      the only independent predictive factor in multivariate analysis. ROC analysis
      identified a cutoff value for baseline RAMRIS synovitis score of 5 (maximum
      possible score 21). Rheumatoid factor (RF) status yielded a significant
      interaction with synovitis (p value = 0.044). RF-positive patients with a RAMRIS
      synovitis score of > 5 vs <= 5, had an OR of 4.4 (95% CI 1.72-11.4) for
      radiographic progression. CONCLUSION: High MRI synovitis score predicts
      radiographic progression in patients in clinical remission/LDA. A cutoff point
      for determining an MRI inflammatory activity acceptable state based on the RAMRIS
      synovitis score was established. Incorporating MRI in future remission criteria
      should be considered.

PMID- 24334648
TI  - The relationship between physical activity levels and pain in children with
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: Pain and reduced physical activity levels are common in children with
      juvenile idiopathic arthritis (JIA). Currently, there is no consensus about the
      role of physical activity in managing pain in JIA. The purpose of our study was
      to assess the relationship between physical activity level and pain in children
      ages 11 to 18 years with JIA. METHODS: A random sample of 50 patients with JIA
      were approached by mailed questionnaires. Physical activity was determined using
      the Physical Activity Questionnaire (PAQ). Pain measures included the Numerical
      Rating Scale (pain severity), SUPER-KIDZ body diagram (number of painful areas),
      and the Child Activities Limitations Inventory-21 (pain interference).
      Generalized linear models were used to assess the relationship between physical
      activity and pain, as well as the roles of sex and age. RESULTS: The response
      rate was 84%. Thirty-four respondents completed the questionnaire package. The
      median age was 15 years. The mean PAQ score was 2.16/5. Physical activity
      declines with increasing age in youth with JIA (r = 0.53, p = 0.0014). Lower
      physical activity is associated with greater pain interference (r = 0.39, p =
      0.0217) and more severe pain (r = 0.35, p = 0.0422). CONCLUSION: Children with
      JIA report significantly less activity than healthy children based on PAQ scores,
      with physical activity declining throughout adolescence. Physical activity is
      inversely related to pain interference and severity in children with JIA. Our
      findings suggest that physical activity interventions may play an important role
      in the management of pain in JIA.

PMID- 24334649
TI  - Plasma adipokine levels and their association with overall burden of painful
      joints among individuals with hip and knee osteoarthritis.
AB  - OBJECTIVE: To investigate the association between plasma adipokine levels and the
      burden of painful joints among individuals with hip and knee osteoarthritis (OA).
      METHODS: Adipokines (leptin, adiponectin, adipsin, resistin) were determined by
      ELISA (n = 78). Individuals reported painful joints on a homunculus. Associations
      were examined by sex-stratified Poisson analyses. RESULTS: Adjusted for age, body
      mass index, and hip/knee OA, higher leptin and adiponectin and lower adipsin
      levels were associated with greater painful joint burden (i.e., counts) among
      women (p < 0.01). Among men, higher resistin levels were associated with lower
      counts (p = 0.03). CONCLUSION: Findings support the likelihood of a systemic
      dependent sex-specific pain burden among individuals with OA.

PMID- 24334650
TI  - Inflammation and disease activity are associated with high circulating cardiac
      markers in rheumatoid arthritis independently of traditional cardiovascular risk
      factors.
AB  - OBJECTIVE: To measure concentrations of high-sensitivity cardiac troponin (HS
      cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with
      rheumatoid arthritis (RA) and to examine correlates. METHODS: The plasma
      concentrations of HS-cTnT and NT-proBNP were measured in consecutive patients
      with RA and compared to values obtained from age-matched and sex-matched healthy
      controls. RESULTS: We included 236 unrelated patients with RA (192 females, 57 +/
      13 yrs) and 213 controls (170 females, 55 +/- 15 yrs). Seventy-one patients with
      RA were free of cardiovascular (CV) risk factors. HS-cTnT and NT-proBNP
      concentrations were significantly higher in the total cohort of patients with RA
      (p = 0.03 and p < 0.0001, respectively) and in the subgroup free of CV risk
      factors (p = 0.02 and p < 0.0001, respectively) compared to controls. In
      addition, both the total cohort of patients with RA and the subgroup free of CV
      risk factors were more likely to have levels above the cutoff concentrations of
      HS-cTnT (p = 0.003 and p = 0.007, respectively) and NT-proBNP (p = 0.0001 and p <
      0.0001, respectively) than controls. Patients with RA and increased C-reactive
      protein (CRP) levels had higher HS-cTnT (p = 0.03) and NT-proBNP (p = 0.02)
      concentrations. HS-cTnT levels positively correlated with the 28-joint Disease
      Activity Score (DAS28-CRP; r = 0.2, p = 0.020). Multivariate logistic regression
      analysis indicated that increased HS-cTnT levels were independently associated
      with a DAS28-CRP > 5.1 (OR 11.8; 95% CI 1.6-35.5) and a body mass index > 30
      kg/m(2) (OR 2.7; 95% CI 1.3-5.5). CONCLUSION: HS-cTnT and NTproBNP are increased
      in patients with RA, independent of CV risk factors. The association between HS
      cTnT, NT-proBNP, and CRP, together with the correlation between HS-cTnT and
      disease activity, support the link between myocardial injury/dysfunction and
      inflammation.

PMID- 24334651
TI  - OMERACT endorsement of measures of outcome for studies of acute gout.
AB  - OBJECTIVE: To determine the extent to which participants at the Outcome Measures
      in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical
      trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT
      filter requirements of truth, discrimination, and feasibility; and where future
      research efforts need to be directed. METHODS: Results of a systematic literature
      review and analysis of individual-level data from recent clinical studies of
      acute gout were presented to OMERACT participants. The information was discussed
      in breakout groups, and opinion was defined by subsequent voting in a plenary
      session. Endorsement was defined as at least 70% of participants voting in
      agreement with the proposition (where the denominator excluded those participants
      who did not vote or who voted "don't know"). RESULTS: The following measures were
      endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale
      and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert
      scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4)
      5-point Likert scale for patient global assessment of response to treatment.
      Measures for the activity limitations domain were not endorsed. CONCLUSION:
      Measures of pain, joint swelling, joint tenderness, and patient global assessment
      in acute gout were endorsed at OMERACT 11. These measures should now be used in
      clinical trials of acute gout.

PMID- 24334653
TI  - Atomically resolved STM imaging with a diamond tip: simulation and experiment.
AB  - The spatial resolution of a scanning tunneling microscope (STM) can be enhanced
      using light element-terminated probes with spatially localized electron orbitals
      at the apex atom. Conductive diamond probes can provide carbon atomic orbitals
      suitable for STM imaging with sub-Angstrom lateral resolution and high apex
      stability crucial for the small tunneling gaps necessary for high-resolution
      experiments. Here we demonstrate that high spatial resolution can be achieved in
      STM experiments with single-crystal diamond tips, which are generally only
      considered for use as probes for atomic force microscopy. The results of STM
      experiments with a heavily boron-doped, diamond probe on a graphite surface;
      density functional theory calculations of the tip and surface electronic
      structure; and first-principles tunneling current calculations demonstrate that
      the highest spatial resolution can be achieved with diamond tips at tip-sample
      distances of 3-5 A when frontier p-orbitals of the tip provide their maximum
      contribution to the tunneling current. At the same time, atomic resolution is
      feasible even at extremely small gaps with very high noise in the tunneling
      current.

PMID- 24334652
TI  - Outcome measures in acute gout: a systematic literature review.
AB  - OBJECTIVE: Five core domains have been endorsed by Outcome Measures in
      Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness,
      patient global assessment, and activity limitation. We evaluated instruments for
      these domains according to the OMERACT filter: truth, feasibility, and
      discrimination. METHODS: A systematic search strategy for instruments used to
      measure the acute gout core domains was formulated. For each method, articles
      were assessed by 2 reviewers to summarize information according to the specific
      components of the OMERACT filter. RESULTS: Seventy-seven articles and abstracts
      met the inclusion criteria. Pain was most frequently reported (76 studies, 20
      instruments). The pain instruments used most often were 100 mm visual analog
      scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face
      and content validity, and within- and between-group discrimination. Four-point
      Likert scales assessing index joint swelling and tenderness have been used in
      numerous acute gout studies; these instruments are feasible, with high face and
      content validity, and show within- and between-group discrimination. Five-point
      Patient Global Assessment of Response to Treatment (PGART) scales are feasible
      and valid, and show within- and between-group discrimination. Measures of
      activity limitations were infrequently reported, and insufficient data were
      available to make definite assessments of the instruments for this domain.
      CONCLUSION: Many different instruments have been used to assess the acute gout
      core domains. Pain VAS and 5-point Likert scales, 4-point Likert scales of index
      joint swelling and tenderness and 5-point PGART instruments meet the criteria for
      the OMERACT filter.

PMID- 24334654
TI  - Atomic structure evolution during solidification of liquid niobium from ab initio
      molecular dynamics simulations.
AB  - Atomic structure transitions of liquid niobium during solidification, at
      different temperatures from 3200 to 1500 K, were studied by using ab initio
      molecular dynamics simulations. The local atomic structure variations with
      temperature are investigated by using the pair-correlation function, the
      structure factor, the bond-angle distribution function, the Honeycutt-Anderson
      index, Voronoi tessellation and the cluster alignment methods. Our results
      clearly show that, upon quenching, the icosahedral short-range order dominates in
      the stable liquid and supercooled liquid states before the system transforms to
      crystalline body-center cubic phase at a temperature of about 1830 K. 

PMID- 24334655
TI  - Fabrication of highly ordered Ta2O5 and Ta3N5 nanorod arrays by nanoimprinting
      and through-mask anodization.
AB  - Using highly ordered porous anodic alumina membrane fabricated with the aid of
      nanoimprinting as a mask, Ta2O5 nanorod array with uniform diameter, length, and
      distribution is grown in situ on a Ta substrate by through-mask anodization. The
      Ta2O5 nanorod array is further transformed into Ta3N5 nanorod array without
      damaging the nanorod structure by nitridation. Solar-driven photoelectrochemical
      water splitting with a maximum solar energy conversion efficiency of 0.36% is
      demonstrated with the Ta3N5 nanorod array after modifying the surface with cobalt
      phosphate as a co-catalyst. The Ta2O5 and Ta3N5 nanorod arrays have potential
      applications in catalysis, photonics, UV photodetection and solar energy
      conversion. 

PMID- 24334656
TI  - Armenia: health system review.
AB  - This analysis of the Armenian health system reviews the developments in
      organization and governance, health financing, healthcare provision, health
      reforms and health system performance since 2006. Armenia inherited a Semashko
      style health system on independence from the Soviet Union in 1991. Initial severe
      economic and sociopolitical difficulties during the 1990s affected the population
      health, though strong economic growth from 2000 benefited the populations health.
      Nevertheless, the Armenian health system remains unduly tilted towards inpatient
      care concentrated in the capital city despite overall reductions in hospital beds
      and concerted efforts to reform primary care provision. Changes in health system
      financing since independence have been more profound, as out-of-pocket (OOP)
      payments now account for over half of total health expenditure. This reduces
      access to essential services for the poorest households - particularly for
      inpatient care and pharmaceuticals - and many households face catastrophic health
      expenditure. Improving health system performance and financial equity are
      therefore the key challenges for health system reform. The scaling up of some
      successful recent programmes for maternal and child health may offer solutions,
      but require sustained financial resources that will be challenging in the context
      of financial austerity and the low base of public financing. 

PMID- 24334657
TI  - Corticospinal tract integrity and lesion volume play different roles in chronic
      hemiparesis and its improvement through motor practice.
AB  - BACKGROUND: Initial evidence suggests that the integrity of the ipsilesional
      corticospinal tract (CST) after stroke is strongly related to motor function in
      the chronic state but not the treatment gain induced by motor rehabilitation.
      OBJECTIVE: We examined the association of motor status and treatment benefit by
      testing patients with a wide range of severity of hemiparesis of the left and
      right upper extremity. METHOD: Diffusion tensor imaging was performed in 22
      patients beyond 12 months after onset of stroke with severe to moderate
      hemiparesis. Motor function was tested before and after 2 weeks of modified
      constraint-induced movement therapy. RESULTS: CST integrity, but not lesion
      volume, correlated with the motor ability measures of the Wolf Motor Function
      Test and the Motor Activity Log. No differences were found between left and right
      hemiparesis. Motor performance improved significantly with the treatment regime,
      and did so equally for patients with left and right arm paresis. However,
      treatment benefit was not associated with either CST integrity or lesion volume.
      CONCLUSION: CST integrity correlated best in this small trial with chronic long
      term status but not treatment-induced improvements. The CST may play a different
      role in the mechanisms mediating long-term outcome compared to those underlying
      practice-induced gains after a chronic plateau in motor function.

PMID- 24334658
TI  - Regio- and stereospecific hydroxylation of various steroids at the 16alpha
      position of the D ring by the Streptomyces griseus cytochrome P450 CYP154C3.
AB  - Cytochrome P450 monooxygenases (P450s), which constitute a superfamily of heme
      containing proteins, catalyze the direct oxidation of a variety of compounds in a
      regio- and stereospecific manner; therefore, they are promising catalysts for use
      in the oxyfunctionalization of chemicals. In the course of our comprehensive
      substrate screening for all 27 putative P450s encoded by the Streptomyces griseus
      genome, we found that Escherichia coli cells producing an S. griseus P450
      (CYP154C3), which was fused C terminally with the P450 reductase domain (RED) of
      a self-sufficient P450 from Rhodococcus sp., could transform various steroids
      (testosterone, progesterone, Delta(4)-androstene-3,17-dione, adrenosterone, 1,4
      androstadiene-3,17-dione, dehydroepiandrosterone, 4-pregnane-3,11,20-trione, and
      deoxycorticosterone) into their 16alpha-hydroxy derivatives as determined by
      nuclear magnetic resonance and high-resolution mass spectrometry analyses. The
      purified CYP154C3, which was not fused with RED, also catalyzed the regio- and
      stereospecific hydroxylation of these steroids at the same position with the aid
      of ferredoxin and ferredoxin reductase from spinach. The apparent equilibrium
      dissociation constant (Kd) values of the binding between CYP154C3 and these
      steroids were less than 8 MUM as determined by the heme spectral change,
      indicating that CYP154C3 strongly binds to these steroids. Furthermore, kinetic
      parameters of the CYP154C3-catalyzed hydroxylation of Delta(4)-androstene-3,17
      dione were determined (Km, 31.9 +/- 9.1 MUM; kcat, 181 +/- 4.5 s(-1)). We
      concluded that CYP154C3 is a steroid D-ring 16alpha-specific hydroxylase which
      has considerable potential for industrial applications. This is the first
      detailed enzymatic characterization of a P450 enzyme that has a steroid D-ring
      16alpha-specific hydroxylation activity. 

PMID- 24334659
TI  - The presence of conjugative plasmid pLS20 affects global transcription of Its
      Bacillus subtilis host and confers beneficial stress resistance to cells.
AB  - Conjugation activity of plasmid pLS20 from Bacillus subtilis subsp. natto is
      induced when cells are diluted into fresh medium and diminishes as cells enter
      into stationary-phase growth. Transcriptional profiling shows that during mid
      exponential growth, more than 5% of the host genes are affected in the presence
      of the plasmid, in contrast to the minor changes seen in freshly diluted and
      stationary-phase cells. Changes occurred in many metabolic pathways, although
      pLS20 does not confer any detectable burden on its host cell, as well as in
      membrane and cell wall-associated processes, in the large motility operon, and in
      several other cellular processes. In agreement with these changes, we found
      considerable alterations in motility and enzyme activity and increased resistance
      against several different forms of stress in cells containing the plasmid,
      revealing that the presence of pLS20 has a broad impact on the physiology of its
      host cell and increases its stress resistance in multiple aspects. Additionally,
      we found that the lack of chromosomal gene yueB, known to encode a phage receptor
      protein, which is upregulated in cells containing pLS20, strongly reduced
      conjugation efficiency, revealing that pLS20 not only increases fitness of its
      host but also employs host proteins for efficient transfer into a new cell. 

PMID- 24334660
TI  - Cross-institute evaluations of inhibitor-resistant PCR reagents for direct
      testing of aerosol and blood samples containing biological warfare agent DNA.
AB  - Rapid pathogen detection is crucial for the timely introduction of therapeutics.
      Two groups (one in the United Kingdom and one in the United States) independently
      evaluated inhibitor-resistant PCR reagents for the direct testing of substrates.
      In the United Kingdom, a multiplexed Bacillus anthracis (target) and Bacillus
      subtilis (internal-control) PCR was used to evaluate 4 reagents against 5 PCR
      inhibitors and down-selected the TaqMan Fast Virus 1-Step master mix (Life
      Technologies Inc.). In the United States, four real-time PCR assays (targeting B.
      anthracis, Brucella melitensis, Venezuelan equine encephalitis virus [VEEV], and
      Orthopoxvirus spp.) were used to evaluate 5 reagents (plus the Fast Virus master
      mix) against buffer, blood, and soil samples and down-selected the KAPA Blood
      Direct master mix (KAPA Biosystems Inc.) with added Platinum Taq (Life
      Technologies). The down-selected reagents underwent further testing. In the
      United Kingdom experiments, both reagents were tested against seven contrived
      aerosol collector samples containing B. anthracis Ames DNA and B. subtilis spores
      from a commercial formulation (BioBall). In PCR assays with reaction mixtures
      containing 40% crude sample, an airfield-collected sample induced inhibition of
      the B. subtilis PCR with the KAPA reagent and complete failure of both PCRs with
      the Fast Virus reagent. However, both reagents allowed successful PCR for all
      other samples-which inhibited PCRs with a non-inhibitor-resistant reagent. In the
      United States, a cross-assay limit-of-detection (LoD) study in blood was
      conducted. The KAPA Blood Direct reagent allowed the detection of agent DNA (by
      four PCRs) at higher concentrations of blood in the reaction mixture (2.5%) than
      the Fast Virus reagent (0.5%), although LoDs differed between assays and reagent
      combinations. Across both groups, the KAPA Blood Direct reagent was determined to
      be the optimal reagent for inhibition relief in PCR. 

PMID- 24334661
TI  - Assessing the mechanisms responsible for differences between nitrogen
      requirements of saccharomyces cerevisiae wine yeasts in alcoholic fermentation.
AB  - Nitrogen is an essential nutrient for Saccharomyces cerevisiae wine yeasts during
      alcoholic fermentation, and its abundance determines the fermentation rate and
      duration. The capacity to ferment under conditions of nitrogen deficiency differs
      between yeasts. A characterization of the nitrogen requirements of a set of 23
      strains revealed large differences in their fermentative performances under
      nitrogen deficiency, and these differences reflect the nitrogen requirements of
      the strains. We selected and compared two groups of strains, one with low
      nitrogen requirements (LNRs) and the other with high nitrogen requirements
      (HNRs). A comparison of various physiological traits indicated that the
      differences are not related to the ability to store nitrogen or the protein
      content. No differences in protein synthesis activity were detected between
      strains with different nitrogen requirements. Transcriptomic analysis revealed
      expression patterns specific to each of the two groups of strains, with an
      overexpression of stress genes in HNR strains and a stronger expression of
      biosynthetic genes in LNR strains. Our data suggest that differences in
      glycolytic flux may originate from variations in nitrogen sensing and signaling
      under conditions of starvation. 

PMID- 24334662
TI  - The third replicon of members of the Burkholderia cepacia Complex, plasmid pC3,
      plays a role in stress tolerance.
AB  - The metabolically versatile Burkholderia cepacia complex (Bcc) occupies a variety
      of niches, including the plant rhizosphere and the cystic fibrosis lung (where it
      is often fatal to the patient). Bcc members have multipartite genomes, of which
      the third replicon, pC3 (previously chromosome 3), has been shown to be a
      nonessential megaplasmid which confers virulence and both antifungal and
      proteolytic activity on several strains. In this study, pC3 curing was extended
      to cover strains of 16 of the 17 members of the Bcc, and the phenotypes conferred
      by pC3 were determined. B. cenocepacia strains H111, MCO-3, and HI2424 were
      previously cured of pC3; however, this had not proved possible in the epidemic
      strain K56-2. Here, we investigated the mechanism of this unexpected stability
      and found that efficient toxin-antitoxin systems are responsible for maintaining
      pC3 of strain K56-2. Identification of these systems allowed neutralization of
      the toxins and the subsequent deletion of K56-2pC3. The cured strain was found to
      exhibit reduced antifungal activity and was attenuated in both the zebrafish and
      the Caenorhabditis elegans model of infection. We used a PCR screening method to
      examine the prevalence of pC3 within 110 Bcc isolates and found that this
      replicon was absent in only four cases, suggesting evolutionary fixation. It is
      shown that plasmid pC3 increases the resistance of B. cenocepacia H111 to various
      stresses (oxidative, osmotic, high-temperature, and chlorhexidine-induced
      stresses), explaining the prevalence of this replicon within the Bcc. 

PMID- 24334664
TI  - Discovery of novel Rickettsiella spp. in ixodid ticks from Western Canada.
AB  - The genomic DNA from four species of ixodid ticks in western Canada was tested
      for the presence of Rickettsiella by PCR analyses targeting the 16S rRNA gene.
      Eighty-eight percent of the Ixodes angustus (n = 270), 43% of the I. sculptus (n
      = 61), and 4% of the I. kingi (n = 93) individuals examined were PCR positive for
      Rickettsiella, whereas there was no evidence for the presence of Rickettsiella in
      Dermacentor andersoni (n = 45). Three different single-strand conformation
      polymorphism profiles of the 16S rRNA gene were detected among amplicons derived
      from Rickettsiella-positive ticks, each corresponding to a different sequence
      type. Furthermore, each sequence type was associated with a different tick
      species. Phylogenetic analyses of sequence data of the 16S rRNA gene and three
      other genes (rpsA, gidA, and sucB) revealed that all three sequence types were
      placed in a clade that contained species and pathotypes of the genus
      Rickettsiella. The bacterium in I. kingi represented the sister taxon to the
      Rickettsiella in I. sculptus, and both formed a clade with Rickettsiella grylli
      from crickets (Gryllus bimaculatus) and "R. ixodidis" from I. woodi. In contrast,
      the Rickettsiella in I. angustus was not a member of this clade but was placed
      external to the clade comprising the pathotypes of R. popilliae. The results
      indicate the existence of at least two new species of Rickettsiella: one in I.
      angustus and another in I. kingi and I. sculptus. However, the Rickettsiella
      strains in I. kingi and I. sculptus may also represent different species because
      each had unique sequences for all four genes. 

PMID- 24334665
TI  - Lineage-specific distribution of insertion sequence excision enhancer in
      enterotoxigenic Escherichia coli isolated from swine.
AB  - Insertion sequences (ISs) are the simplest transposable elements and are widely
      distributed in bacteria; however, they also play important roles in genome
      evolution. We recently identified a protein called IS excision enhancer (IEE) in
      enterohemorrhagic Escherichia coli (EHEC) O157. IEE promotes the excision of IS
      elements belonging to the IS3 family, such as IS629, as well as several other
      families. IEE-mediated IS excision generates various genomic deletions that lead
      to the diversification of the bacterial genome. IEE has been found in a broad
      range of bacterial species; however, among sequenced E. coli strains, IEE is
      primarily found in EHEC isolates. In this study, we investigated non-EHEC
      pathogenic E. coli strains isolated from domestic animals and found that IEE is
      distributed in specific lineages of enterotoxigenic E. coli (ETEC) strains of
      serotypes O139 or O149 isolated from swine. The iee gene is located within
      integrative elements that are similar to SpLE1 of EHEC O157. All iee-positive
      ETEC lineages also contained multiple copies of IS629, a preferred substrate of
      IEE, and their genomic locations varied significantly between strains, as
      observed in O157. These data suggest that IEE may have been transferred among
      EHEC and ETEC in swine via SpLE1 or SpLE1-like integrative elements. In addition,
      IS629 is actively moving in the ETEC O139 and O149 genomes and, as in EHEC O157,
      is promoting the diversification of these genomes in combination with IEE. 

PMID- 24334663
TI  - Association of clustered regularly interspaced short palindromic repeat (CRISPR)
      elements with specific serotypes and virulence potential of shiga toxin-producing
      Escherichia coli.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains (n = 194) representing 43
      serotypes and E. coli K-12 were examined for clustered regularly interspaced
      short palindromic repeat (CRISPR) arrays to study genetic relatedness among STEC
      serotypes. A subset of the strains (n = 81) was further analyzed for subtype I-E
      cas and virulence genes to determine a possible association of CRISPR elements
      with potential virulence. Four types of CRISPR arrays were identified. CRISPR1
      and CRISPR2 were present in all strains tested; 1 strain also had both CRISPR3
      and CRISPR4, whereas 193 strains displayed a short, combined array, CRISPR3-4. A
      total of 3,353 spacers were identified, representing 528 distinct spacers. The
      average length of a spacer was 32 bp. Approximately one-half of the spacers (54%)
      were unique and found mostly in strains of less common serotypes. Overall, CRISPR
      spacer contents correlated well with STEC serotypes, and identical arrays were
      shared between strains with the same H type (O26:H11, O103:H11, and O111:H11).
      There was no association identified between the presence of subtype I-E cas and
      virulence genes, but the total number of spacers had a negative correlation with
      potential pathogenicity (P < 0.05). Fewer spacers were found in strains that had
      a greater probability of causing outbreaks and disease than in those with lower
      virulence potential (P < 0.05). The relationship between the CRISPR-cas system
      and potential virulence needs to be determined on a broader scale, and the
      biological link will need to be established. 

PMID- 24334666
TI  - Alcoholytic cleavage of polyhydroxyalkanoate chains by class IV synthases induced
      by endogenous and exogenous ethanol.
AB  - Polyhydroxyalkanoate (PHA)-producing Bacillus strains express class IV PHA
      synthase, which is composed of the subunits PhaR and PhaC. Recombinant
      Escherichia coli expressing PHA synthase from Bacillus cereus strain YB-4
      (PhaRCYB-4) showed an unusual reduction of the molecular weight of PHA produced
      during the stationary phase of growth. Nuclear magnetic resonance analysis of the
      low-molecular-weight PHA revealed that its carboxy end structure was capped by
      ethanol, suggesting that the molecular weight reduction was the result of
      alcoholytic cleavage of PHA chains by PhaRCYB-4 induced by endogenous ethanol.
      This scission reaction was also induced by exogenous ethanol in both in vivo and
      in vitro assays. In addition, PhaRCYB-4 was observed to have alcoholysis activity
      for PHA chains synthesized by other synthases. The PHA synthase from Bacillus
      megaterium (PhaRCBm) from another subgroup of class IV synthases was also assayed
      and was shown to have weak alcoholysis activity for PHA chains. These results
      suggest that class IV synthases may commonly share alcoholysis activity as an
      inherent feature. 

PMID- 24334667
TI  - Deregulation of feedback inhibition of phosphoenolpyruvate carboxylase for
      improved lysine production in Corynebacterium glutamicum.
AB  - Allosteric regulation of phosphoenolpyruvate carboxylase (PEPC) controls the
      metabolic flux distribution of anaplerotic pathways. In this study, the feedback
      inhibition of Corynebacterium glutamicum PEPC was rationally deregulated, and its
      effect on metabolic flux redistribution was evaluated. Based on rational protein
      design, six PEPC mutants were designed, and all of them showed significantly
      reduced sensitivity toward aspartate and malate inhibition. Introducing one of
      the point mutations (N917G) into the ppc gene, encoding PEPC of the lysine
      producing strain C. glutamicum LC298, resulted in ~37% improved lysine
      production. In vitro enzyme assays and (13)C-based metabolic flux analysis showed
      ca. 20 and 30% increases in the PEPC activity and corresponding flux,
      respectively, in the mutant strain. Higher demand for NADPH in the mutant strain
      increased the flux toward pentose phosphate pathway, which increased the supply
      of NADPH for enhanced lysine production. The present study highlights the
      importance of allosteric regulation on the flux control of central metabolism.
      The strategy described here can also be implemented to improve other oxaloacetate
      derived products. 

PMID- 24334668
TI  - Functional analysis of environmental DNA-derived microviridins provides new
      insights into the diversity of the tricyclic peptide family.
AB  - Microviridins represent a unique family of ribosomally synthesized cage-like
      depsipeptides from cyanobacteria with potent protease-inhibitory activities. The
      natural diversity of these peptides is largely unexplored. Here, we describe two
      methodologies that were developed to functionally characterize cryptic
      microviridin gene clusters from metagenomic DNA. Environmental samples were
      collected and enriched from cyanobacterial freshwater blooms of different
      geographical origins containing predominantly Microcystis sp. Microviridins were
      produced either directly from fosmid clones or after insertion of environmental
      DNA-derived gene cassettes into a minimal expression platform in Escherichia
      coli. Three novel microviridin variants were isolated and tested against
      different serine-type proteases. The comparison of the bioactivity profiles of
      the new congeners allows deduction of further structure-function relationships
      for microviridins. Moreover, this study provides new insights into microviridin
      processing and gene cluster organization. 

PMID- 24334669
TI  - Ubiquity of insect-derived nitrogen transfer to plants by endophytic insect
      pathogenic fungi: an additional branch of the soil nitrogen cycle.
AB  - The study of symbiotic nitrogen transfer in soil has largely focused on nitrogen
      fixing bacteria. Vascular plants can lose a substantial amount of their nitrogen
      through insect herbivory. Previously, we showed that plants were able to
      reacquire nitrogen from insects through a partnership with the endophytic, insect
      pathogenic fungus Metarhizium robertsii. That is, the endophytic capability and
      insect pathogenicity of M. robertsii are coupled so that the fungus acts as a
      conduit to provide insect-derived nitrogen to plant hosts. Here, we assess the
      ubiquity of this nitrogen transfer in five Metarhizium species representing those
      with broad (M. robertsii, M. brunneum, and M. guizhouense) and narrower insect
      host ranges (M. acridum and M. flavoviride), as well as the insect-pathogenic
      fungi Beauveria bassiana and Lecanicillium lecanii. Insects were injected with
      (15)N-labeled nitrogen, and we tracked the incorporation of (15)N into two
      dicots, haricot bean (Phaseolus vulgaris) and soybean (Glycine max), and two
      monocots, switchgrass (Panicum virgatum) and wheat (Triticum aestivum), in the
      presence of these fungi in soil microcosms. All Metarhizium species and B.
      bassiana but not L. lecanii showed the capacity to transfer nitrogen to plants,
      although to various degrees. Endophytic association by these fungi increased
      overall plant productivity. We also showed that in the field, where microbial
      competition is potentially high, M. robertsii was able to transfer insect-derived
      nitrogen to plants. Metarhizium spp. and B. bassiana have a worldwide
      distribution with high soil abundance and may play an important role in the
      ecological cycling of insect nitrogen back to plant communities. 

PMID- 24334670
TI  - The Legionella pneumophila collagen-like protein mediates sedimentation,
      autoaggregation, and pathogen-phagocyte interactions.
AB  - Although only partially understood, multicellular behavior is relatively common
      in bacterial pathogens. Bacterial aggregates can resist various host defenses and
      colonize their environment more efficiently than planktonic cells. For the
      waterborne pathogen Legionella pneumophila, little is known about the roles of
      autoaggregation or the parameters which allow cell-cell interactions to occur.
      Here, we determined the endogenous and exogenous factors sufficient to allow
      autoaggregation to take place in L. pneumophila. We show that isolates from
      Legionella species which do not produce the Legionella collagen-like protein
      (Lcl) are deficient in autoaggregation. Targeted deletion of the Lcl-encoding
      gene (lpg2644) and the addition of Lcl ligands impair the autoaggregation of L.
      pneumophila. In addition, Lcl-induced autoaggregation requires divalent cations.
      Escherichia coli producing surface-exposed Lcl is able to autoaggregate and shows
      increased biofilm production. We also demonstrate that L. pneumophila infection
      of Acanthamoeba castellanii and Hartmanella vermiformis is potentiated under
      conditions which promote Lcl dependent autoaggregation. Overall, this study shows
      that L. pneumophila is capable of autoaggregating in a process that is mediated
      by Lcl in a divalent-cation-dependent manner. It also reveals that Lcl
      potentiates the ability of L. pneumophila to come in contact, attach, and infect
      amoebae. 

PMID- 24334671
TI  - Analysis of the transcriptional regulator GlpR, promoter elements, and
      posttranscriptional processing involved in fructose-induced activation of the
      phosphoenolpyruvate-dependent sugar phosphotransferase system in Haloferax
      mediterranei.
AB  - Among all known archaeal strains, the phosphoenolpyruvate-dependent
      phosphotransferase system (PTS) for fructose utilization is used primarily by
      haloarchaea, which thrive in hypersaline environments, whereas the molecular
      details of the regulation of the archaeal PTS under fructose induction remain
      unclear. In this study, we present a comprehensive examination of the regulatory
      mechanism of the fructose PTS in the haloarchaeon Haloferax mediterranei. With
      gene knockout and complementation, microarray analysis, and chromatin
      immunoprecipitation-quantitative PCR (ChIP-qPCR), we revealed that GlpR is the
      indispensable activator, which specifically binds to the PTS promoter (PPTS)
      during fructose induction. Further promoter-scanning mutation indicated that
      three sites located upstream of the H. mediterranei PPTS, which are conserved in
      most haloarchaeal PPTSs, are involved in this induction. Interestingly, two PTS
      transcripts (named T8 and T17) with different lengths of 5' untranslated region
      (UTR) were observed, and promoter or 5' UTR swap experiments indicated that the
      shorter 5' UTR was most likely generated from the longer one. Notably, the
      translation efficiency of the transcript with this shorter 5' UTR was
      significantly higher and the ratio of T8 (with the shorter 5' UTR) to T17
      increased during fructose induction, implying that a posttranscriptional
      mechanism is also involved in PTS activation. With these insights into the
      molecular regulation of the haloarchaeal PTS, we have proposed a working model
      for haloarchaea in response to environmental fructose. 

PMID- 24334672
TI  - Survival and transmission of potato virus Y, pepino mosaic virus, and potato
      spindle tuber viroid in water.
AB  - Hydroponic systems and intensive irrigation are used widely in horticulture and
      thus have the potential for rapid spread of water-transmissible plant pathogens.
      Numerous plant viruses have been reported to occur in aqueous environments,
      although information on their survival and transmission is minimal, due mainly to
      the lack of effective detection methods and to the complexity of the required
      transmission experiments. We have assessed the role of water as a source of plant
      infection using three mechanically transmissible plant pathogens that constitute
      a serious threat to tomato and potato production: pepino mosaic virus (PepMV),
      potato virus Y (PVY), and potato spindle tuber viroid (PSTVd). PepMV remains
      infectious in water at 20 +/- 4 degrees C for up to 3 weeks, PVY (NTN strain) for
      up to 1 week, and PSTVd for up to 7 weeks. Experiments using a hydroponic system
      show that PepMV (Ch2 genotype) and PVY (NTN strain) can be released from plant
      roots into the nutrient solution and can infect healthy plants through their
      roots, ultimately spreading to the green parts, where they can be detected after
      a few months. In addition, tubers developed on plants grown in substrate watered
      with PSTVd-infested water were confirmed to be the source of viroid infection.
      Our data indicate that although well-known pathways of virus spread are more
      rapid than water-mediated infection, like insect or mechanical transmission
      through leaves, water is a route that provides a significant bridge for rapid
      virus/viroid spread. Consequently, water should be taken into account in future
      epidemiology and risk assessment studies. 

PMID- 24334673
TI  - Phylogeography of cylindrospermopsin and paralytic shellfish toxin-producing
      nostocales cyanobacteria from mediterranean europe (Spain).
AB  - Planktonic Nostocales cyanobacteria represent a challenge for microbiological
      research because of the wide range of cyanotoxins that they synthesize and their
      invasive behavior, which is presumably enhanced by global warming. To gain
      insight into the phylogeography of potentially toxic Nostocales from
      Mediterranean Europe, 31 strains of Anabaena (Anabaena crassa, A. lemmermannii,
      A. mendotae, and A. planctonica), Aphanizomenon (Aphanizomenon gracile, A.
      ovalisporum), and Cylindrospermopsis raciborskii were isolated from 14 freshwater
      bodies in Spain and polyphasically analyzed for their phylogeography, cyanotoxin
      production, and the presence of cyanotoxin biosynthesis genes. The potent
      cytotoxin cylindrospermopsin (CYN) was produced by all 6 Aphanizomenon
      ovalisporum strains at high levels (5.7 to 9.1 MUg CYN mg(-1) [dry weight]) with
      low variation between strains (1.5 to 3.9-fold) and a marked extracellular
      release (19 to 41% dissolved CYN) during exponential growth. Paralytic shellfish
      poisoning (PSP) neurotoxins (saxitoxin, neosaxitoxin, and decarbamoylsaxitoxin)
      were detected in 2 Aphanizomenon gracile strains, both containing the sxtA gene.
      This gene was also amplified in non-PSP toxin-producing Aphanizomenon gracile and
      Aphanizomenon ovalisporum. Phylogenetic analyses supported the species
      identification and confirmed the high similarity of Spanish Anabaena and
      Aphanizomenon strains with other European strains. In contrast,
      Cylindrospermopsis raciborskii from Spain grouped together with American strains
      and was clearly separate from the rest of the European strains, raising questions
      about the current assumptions of the phylogeography and spreading routes of C.
      raciborskii. The present study confirms that the nostocalean genus Aphanizomenon
      is a major source of CYN and PSP toxins in Europe and demonstrates the presence
      of the sxtA gene in CYN-producing Aphanizomenon ovalisporum. 

PMID- 24334675
TI  - Role of the study pathologist.
AB  - Toxicologic pathology relies on many disciplines of toxicology and basic sciences
      and often requires other fields and skills such as biostatistics, study design,
      guidelines, and knowledge of Good Laboratory Practices (GLP) regulations.
      Pathology is an integrative discipline where specific training and experience are
      required in order to integrate chemical or biological structures, molecular
      biology, physiology, and morphology for candidate selection and early development
      of a test article and to help in the design of appropriate preclinical/toxicology
      studies. Experience does matter and successful learning is determined by personal
      behavior; pathologists who not only read slides but research their topics and
      keep current with the literature are apt to be successful. 

PMID- 24334674
TI  - Proceedings of the 2013 National Toxicology Program Satellite Symposium.
AB  - The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled
      "Pathology Potpourri," was held in Portland, Oregon, in advance of the Society of
      Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to
      present current diagnostic pathology or nomenclature issues to the toxicologic
      pathology community. This article presents summaries of the speakers'
      presentations, including diagnostic or nomenclature issues that were presented,
      along with select images that were used for audience voting and discussion. Some
      lesions and topics covered during the symposium included a caudal tail vertebra
      duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a
      hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis
      carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of
      control rats; hepatoblastoma arising within an adenoma in a mouse; humoral
      hypercalcemia of benignancy in a transgenic mouse; acetaminophen-induced
      hepatotoxicity in rats; electron microscopy images of iatrogenic
      intraerythrocytic inclusions in transgenic mice; questionable hepatocellular
      degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in
      rats; malignant mixed Mullerian tumors/carcinosarcomas in rats; differential
      diagnoses of proliferative lesions of the intestine of rodents; and finally
      obstructive nephropathy caused by melamine poisoning in a rat. 

PMID- 24334676
TI  - Fathers' views on their financial situations, father-child activities, and
      preventing child injuries.
AB  - Unintentional injuries are a leading public health problem for children,
      particularly among those living at lower socioeconomic levels. Parents play an
      important preventive role, and the aim of this study was to examine fathers'
      views on the role of their family financial situation in preventing children's
      injuries. In-depth interviews were conducted with 15 fathers of children 2 to 7
      years living in western Canada. Questions solicited fathers' views about their
      financial situation and their child injury prevention efforts. Data analysis was
      underpinned by masculinity theory and guided by constant comparative grounded
      theory methods. Findings included that fathers living with fewer financial
      limitations emphasized use of safety equipment and aligned themselves with
      provider and protector masculine ideals. Fathers with moderate financial
      constraint described more child-centered safety efforts and efforts to manage
      finances. Those facing greatest constraint demonstrated aspects of marginalized
      masculinities, whereby they acknowledged their economic provider limitations
      while strongly aligning with the protector role. These findings hold relevance
      for development of interventions aimed at reducing child injury risk inequities.
      Taking into account how masculinities may shape their beliefs and practices can
      inform design of father-centered interventions for men living at different points
      on the socioeconomic spectrum. 

PMID- 24334677
TI  - Age at Sexual Debut and Subsequent Sexual Partnering in Adulthood Among American
      Men.
AB  - This study examined the association of sexual debut and sexual partnering among
      men in the United States aged 21 to 44 years who participated in the 2006-2010
      National Survey of Family Growth. Age at debut was categorized as <15 years, 15
      to 17 years, and >=18 years to permit comparison with previous research. Sexual
      partnering was defined as being concurrent, serial monogamist, or monogamist in
      prior year. Eleven percent reported concurrent partnerships and 6% serial
      monogamy. Sexual debut <15 and 15 to 17 years was associated with concurrency
      (adjusted odds ratio [aOR] < 15 = 2.22; 95% confidence interval [CI] = 1.37-3.61;
      aOR 15-17 = 1.69; 95% CI = 1.05-2.74). Irrespective of age at sexual debut,
      interventions to reduce risky lifetime number of partners may prevent risky
      sexual behavior in early adulthood and later in life. 

PMID- 24334678
TI  - Relationships between patient size, dose and image noise under automatic tube
      current modulation systems.
AB  - Automatic tube current modulation (ATCM) systems are now used for the majority of
      CT scans. The principles of ATCM operation are different in CT scanners from
      different manufacturers. Toshiba and GE scanners base the current modulation on a
      target noise setting, while Philips and Siemens scanners use reference image and
      reference mAs concepts respectively. Knowledge of the relationships between
      patient size, dose and image noise are important for CT patient dose
      optimisation. In this study, the CT patient doses were surveyed for 14 CT
      scanners from four different CT scanner manufacturers. The patient cross
      sectional area, the tube current modulation and the image noise from the CT
      images were analysed using in-house software. The Toshiba and GE scanner results
      showed that noise levels are relatively constant but tube currents are dependent
      on patient size. As a result of this there is a wide range in tube current values
      across different patient sizes, and doses for large patients are significantly
      higher in these scanners. In contrast, in the Philips and Siemens scanners, tube
      currents are less dependent on patient size, the range in tube current is
      narrower, and the doses for larger patients are not as high. Image noise is more
      dependent on the patient size. 

PMID- 24334680
TI  - The conductive properties of single DNA molecules studied by torsion tunneling
      atomic force microscopy.
AB  - The conductive properties of single natural lambda-DNA molecules are studied by
      torsion tunneling atomic force microscopy (TR-TUNA). The currents both parallel
      to and perpendicular to the DNA chains are investigated, but only weak or even no
      current signals are detected by TR-TUNA. To improve the conductance of DNA
      molecules, silver and copper metallized DNAs are fabricated and their
      conductivities are checked by TR-TUNA. It is found that for both Cu- and Ag-DNAs,
      the conductivity perpendicular to the DNA chain is enhanced significantly as the
      metal clusters are attached to the DNA chains. But parallel to the chain the
      electrical transport is still weak, most probably due to the 'beads-on-a-string'
      constructions of metallized DNAs. 

PMID- 24334679
TI  - Tumor suppressor genes promote rhabdomyosarcoma progression in p53 heterozygous,
      HER-2/neu transgenic mice.
AB  - Human sarcomas arise suddenly, thus preempting the study of preneoplastic and
      early neoplastic lesions. To explore the natural history of these tumors we
      studied male mice carrying a heterozygous deletion of p53 and an activated HER
      2/neu transgene (BALB-p53Neu mice), that develop urethral rhabdomyosarcomas with
      nearly full penetrance and early onset (4 months of age). Among genes prominently
      upregulated in preneoplastic tissue, and more highly expressed in tumors, we
      found the insulin-like growth factor 2 (Igf2) and tumor suppressors, p19Arf and
      p21Cip1. In urethral tissues of male mice p53 was less expressed than in female
      mice, whereas HER-2/neu was more expressed, a combination not found in other
      skeletal muscles of the same mice that could contribute to the anatomic and
      sexual specificity of BALB-p53Neu rhabdomyosarcoma. Upregulation of p19Arf and
      p21Cip1 was additively determined by HER-2/neu activation and by p53
      inactivation. Silencing of p19Arf or p21Cip1 in rhabdomyosarcoma cell lines can
      inhibit cell growth and motility, thus suggesting that these genes can contribute
      to growth autonomy and malignancy of tumor cells. In vivo injection of gene
      silenced cells highlighted selective variations in organ-specific metastatic
      ability, indicating that overexpression of p19Arf and p21Cip1 controlled both
      tumor cell-intrinsic properties and microenvironmental interactions. The onset of
      pelvic rhabdomyosarcoma in BALB-p53Neu male mice is triggered by the coincidental
      overexpression of HER-2/neu and hypoexpression of the residual p53 allele, that
      foster p53 loss, Igf2 autocriny and overexpression of p19Arf and p21Cip1, a
      phenotype that could provide novel potential targets for cancer prevention and
      therapy. 

PMID- 24334681
TI  - Nucleation dynamics of nanostructural TiO2 films with controllable phases on
      (001) LaAlO3.
AB  - Microstructure evolution and nucleation dynamics of TiO2 nanostructural thin
      films on (001) LaAlO3 substrates grown by the polymer-assisted deposition
      technique have been systematically studied with the increase of annealing
      temperature. Epitaxial anatase TiO2 phase with nanometer-scaled periodic surface
      strip patterns can be achieved when the sample is annealed at 900  degrees  C. It
      is also found that the morphology of the surface pattern is related to the
      ramping rate of the temperature during annealing. The formation of the surface
      strip pattern can be considered to be associated with the diffusion limit growth
      dynamics. The surface pattern structure was found to strongly affect the
      hydrophilic properties of the thin films.

PMID- 24334682
TI  - Are physical fitness levels declining in UK children and should we be worried?

PMID- 24334684
TI  - Enveloped virus-like particle expression of human cytomegalovirus glycoprotein B
      antigen induces antibodies with potent and broad neutralizing activity.
AB  - A prophylactic vaccine to prevent the congenital transmission of human
      cytomegalovirus (HCMV) in newborns and to reduce life-threatening disease in
      immunosuppressed recipients of HCMV-infected solid organ transplants is highly
      desirable. Neutralizing antibodies against HCMV confer significant protection
      against infection, and glycoprotein B (gB) is a major target of such neutralizing
      antibodies. However, one shortcoming of past HCMV vaccines may have been their
      failure to induce high-titer persistent neutralizing antibody responses that
      prevent the infection of epithelial cells. We used enveloped virus-like particles
      (eVLPs), in which particles were produced in cells after the expression of murine
      leukemia virus (MLV) viral matrix protein Gag, to express either full-length CMV
      gB (gB eVLPs) or the full extracellular domain of CMV gB fused with the
      transmembrane and cytoplasmic domains from vesicular stomatitis virus (VSV)-G
      protein (gB-G eVLPs). gB-G-expressing eVLPs induced potent neutralizing
      antibodies in mice with a much greater propensity toward epithelial cell
      neutralizing activity than that induced with soluble recombinant gB protein. An
      analysis of gB antibody binding titers and T-helper cell responses demonstrated
      that high neutralizing antibody titers were not simply due to enhanced
      immunogenicity of the gB-G eVLPs. The cells transiently transfected with gB-G but
      not gB plasmid formed syncytia, consistent with a prefusion gB conformation like
      those of infected cells and viral particles. Two of the five gB-G eVLP-induced
      monoclonal antibodies we examined in detail had neutralizing activities, one of
      which possessed particularly potent epithelial cell-neutralizing activity. These
      data differentiate gB-G eVLPs from gB antigens used in the past and support their
      use in a CMV vaccine candidate with improved neutralizing activity against
      epithelial cell infection. 

PMID- 24334685
TI  - Ocular immune responses in steers following intranasal vaccination with
      recombinant Moraxella bovis cytotoxin adjuvanted with polyacrylic acid.
AB  - Infectious bovine keratoconjunctivitis (IBK) caused by Moraxella bovis is the
      most common eye disease of cattle. The pathogenesis of M. bovis requires the
      expression of pili that enable the organism to attach to the ocular surface and
      an RTX (repeats in the structural toxin) toxin (cytotoxin or hemolysin), which is
      cytotoxic to corneal epithelial cells. In this pilot study, ocular mucosal immune
      responses of steers were measured following intranasal (i.n.) vaccination with a
      recombinant M. bovis cytotoxin adjuvanted with polyacrylic acid. Beef steers were
      vaccinated with either 500 MUg (n = 3) or 200 MUg (n = 3) of recombinant M. bovis
      cytotoxin plus adjuvant. Control group steers (n = 2) were vaccinated with
      adjuvant alone, and all steers were given a booster on day 21. Antigen-specific
      tear IgA and tear IgG, tear cytotoxin-neutralizing antibody responses, and serum
      cytotoxin-neutralizing antibody responses were determined in samples collected
      prevaccination and on days 14, 28, 42, and 55. Changes in tear antigen-specific
      IgA levels from day 0 to days 28, 42, and 55 were significantly different between
      groups; however, in post hoc comparisons between individual group pairs at the
      tested time points, the differences were not significant. Our results suggest
      that i.n. vaccination of cattle with recombinant M. bovis cytotoxin adjuvanted
      with polyacrylic acid effects changes in ocular antigen-specific IgA
      concentrations. The use of intranasally administered recombinant M. bovis
      cytotoxin adjuvanted with polyacrylic acid could provide an alternative to
      parenteral vaccination of cattle for immunoprophylaxis against IBK. 

PMID- 24334686
TI  - Development of a recombinant protein-based enzyme-linked immunosorbent assay for
      diagnosis of Mycoplasma bovis infection in cattle.
AB  - Mycoplasma bovis causes a range of diseases in cattle, including mastitis,
      arthritis, and pneumonia. However, accurate serological diagnosis of infection
      remains problematic. The studies described here aimed to identify an antigen that
      might be used to develop a more specific and sensitive diagnostic assay. A 226
      kDa immunogenic protein was consistently detected in Western blots by antibodies
      in sera from calves experimentally infected with M. bovis. This protein was shown
      to be a membrane protein with lipase activity and was named mycoplasma
      immunogenic lipase A (MilA). Different regions of MilA were expressed in
      Escherichia coli as glutathione S-transferase (GST) fusion proteins and
      recombinant products from the amino-terminal end shown to have strong
      immunoreactivity with M. bovis-specific bovine sera. The most immunoreactive
      fusion protein, GST-MilA-ab, was used to develop indirect IgM and IgG enzyme
      linked immunosorbent assays (ELISAs). The IgM ELISA detected M. bovis-specific
      IgM antibody 2 weeks after infection with 97.1% sensitivity and had a specificity
      of 63.3%, while the IgG ELISA detected M. bovis-specific IgG 3 weeks after
      infection with 92.86% sensitivity and had a specificity of 98.7%, demonstrating
      that the IgG ELISA has potential for use as a sensitive and specific assay for
      detecting infection in cattle. 

PMID- 24334688
TI  - A nonadjuvanted transcutaneous tetanus patch is effective in boosting anti
      tetanus toxoid immune responses.
AB  - Dry tetanus toxoid (TTx) patches were formulated without any adjuvant, with
      excipients to impart antigen stabilization and to enhance skin delivery. The
      booster effects of the TTx patches were assessed using a guinea pig model. The
      study revealed significant rises in TTx IgG titers induced by the TTx patches
      after a low-dose subcutaneous (s.c.) prime with TTx adsorbed to aluminum
      hydroxide. The TTx patch can therefore be considered an effective alternative to
      a subcutaneous booster. 

PMID- 24334689
TI  - Phase III clinical trials comparing the immunogenicity and safety of the vero
      cell-derived Japanese encephalitis vaccine Encevac with those of mouse brain
      derived vaccine by using the Beijing-1 strain.
AB  - The immunogenicity and safety of an inactivated cell culture Japanese
      encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse
      brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical
      multicenter trials conducted in children. The vaccines contain the same Japanese
      encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials
      (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children.
      Each subject was injected with 17 MUg per dose of either CC-JEV or MB-JEV, and
      the immunogenicity and safety of the vaccines were investigated. Trial 1 showed
      that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose.
      Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine
      that has had a good track record regarding its efficacy for a long time, trial 2
      was conducted in 484 healthy children. To improve the stability, CC-JEV was
      converted from a liquid type to a freeze-dried type of vaccine. Each subject was
      injected subcutaneously with either 4 MUg per dose of CC-JEV, 8 MUg per dose of
      CC-JEV, or 17 MUg per dose of MB-JEV twice, at an interval of 2 to 4 weeks,
      followed by an additional booster immunization 1 to 15 months after the primary
      immunization. Based on the results of trial 2, 4 MUg per dose of the freeze-dried
      CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV.
      Encevac was approved and launched in 2011 and has since been in use as a 2nd
      generation Japanese encephalitis vaccine in Japan. (These studies have been
      registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI
      080586 for trials 1 and 2, respectively).

PMID- 24334687
TI  - Large-scale prospective T cell function assays in shipped, unfrozen blood
      samples: experiences from the multicenter TRIGR trial.
AB  - Broad consensus assigns T lymphocytes fundamental roles in inflammatory,
      infectious, and autoimmune diseases. However, clinical investigations have lacked
      fully characterized and validated procedures, equivalent to those of widely
      practiced biochemical tests with established clinical roles, for measuring core T
      cell functions. The Trial to Reduce Insulin-dependent diabetes mellitus in the
      Genetically at Risk (TRIGR) type 1 diabetes prevention trial used consecutive
      measurements of T cell proliferative responses in prospectively collected fresh
      heparinized blood samples shipped by courier within North America. In this
      article, we report on the quality control implications of this simple and
      pragmatic shipping practice and the interpretation of positive- and negative
      control analytes in our assay. We used polyclonal and postvaccination responses
      in 4,919 samples to analyze the development of T cell immunocompetence. We have
      found that the vast majority of the samples were viable up to 3 days from the
      blood draw, yet meaningful responses were found in a proportion of those with
      longer travel times. Furthermore, the shipping time of uncooled samples
      significantly decreased both the viabilities of the samples and the unstimulated
      cell counts in the viable samples. Also, subject age was significantly associated
      with the number of unstimulated cells and T cell proliferation to positive
      activators. Finally, we observed a pattern of statistically significant increases
      in T cell responses to tetanus toxin around the timing of infant vaccinations.
      This assay platform and shipping protocol satisfy the criteria for robust and
      reproducible long-term measurements of human T cell function, comparable to those
      of established blood biochemical tests. We present a stable technology for
      prospective disease-relevant T cell analysis in immunological diseases,
      vaccination medicine, and measurement of herd immunity. 

PMID- 24334691
TI  - Progression of Tokyo Guidelines and Japanese Guidelines for management of acute
      cholangitis and cholecystitis.
AB  - The Japanese Guidelines for management of acute cholangitis and cholecystitis
      were published in 2005 as the first practical guidelines presenting diagnostic
      and severity assessment criteria for these diseases. After the Japanese version,
      the Tokyo Guidelines (TG07) were reported in 2007 as the first international
      practical guidelines. There were some differences between the two guidelines, and
      some weak points in TG07 were pointed out, such as low sensitivity for diagnosis
      and the presence of divergence between severity assessment and clinical judgment
      for acute cholangitis. Therefore, revisions were started to not only make them up
      to date but also concurrent with the same diagnostic and severity assessment
      criteria. The Revision Committee for the revision of TG07 (TGRC) performed
      validation studies of TG07 and new diagnostic and severity assessment criteria of
      acute cholangitis and cholecystitis. These were retrospective multi-institutional
      studies that collected cases of acute cholangitis, cholecystitis, and non
      inflammatory biliary disease. TGRC held 35 meetings as well as international
      email exchanges with co-authors abroad and held three International Meetings.
      Through these efforts, TG13 improved the diagnostic sensitivity for acute
      cholangitis and cholecystitis, and presented criteria with extremely low false
      positive rates. Furthermore, severity assessment criteria adapted for clinical
      use, flowcharts, and many new diagnostic and therapeutic modalities were
      presented. The world's first management bundles of acute cholangitis and
      cholecystitis were also presented. The revised Japanese version was published
      with the same content as TG13. An electronic application of TG13 that can help to
      diagnose and assess the severity of these diseases using the criteria of TG13 was
      made for free download. 

PMID- 24334692
TI  - The effects of thigh corset with side bars suspension in a subject with
      transtibial amputation: a biomechanical investigation.
AB  - This study aims to investigate some biomechanical effects of a thigh corset with
      side bars (TC-SB) on the gait of a transtibial amputee. During two test
      conditions of with/without TC-SB, the angles of prosthetic lower limb joints,
      stride time, stance time and maximum vertical ground reaction force were
      evaluated. Only the angle of hip joint at initial contact and its maximum flexion
      at swing phase had significant changes (P < 0.05). This may suggest the amputee
      has used a compensatory mechanism to overcome the additional weight of the TC-SB
      suspension. It seems that the participated amputee has no need for this auxiliary
      suspension. 

PMID- 24334693
TI  - Characteristics of a real time monitor using the interference enhanced reflection
      method for organic vapors.
AB  - Performance and sensor characteristics of a monitor for volatile organic
      compounds (VOC monitor) using the interference enhanced reflection (IER) method
      were investigated for 52 organic solvent vapors that are designated as class 1
      and class 2 organic solvents by the Ordinance of Organic Solvent Poisoning
      Prevention in Japan. Test vapors were prepared by injecting 1 to 3 MUl of liquid
      solvent into a 20 l Tedlar((r)) bag and perfectly vaporizing them. The vapor
      concentration was simultaneously measured with the monitor and a gas
      chromatograph (GC) equipped with flame ionization detector, and both values were
      compared. The monitor could detect all the solvent vapors that we used. Linear
      response was obtained between the concentration measured by the monitor and those
      by the GC. The monitor could detect 1/10 of the administrative control level for
      37 of 52 solvent vapors, including toluene and xylenes. For 15 vapors, on the
      other hand, the monitor could not be used for the working environment measurement
      because the sensor response was low or the regression lines did not pass through
      the origin.

PMID- 24334694
TI  - [A review of 13 cases of obturator hernia].
AB  - We reviewed clinical features of patients who we treated for obturator hernia.
      The subjects were 13 patients who underwent an operation for obturator hernia in
      our hospital between April 2002 and December 2012. The mean age was 78.5 years,
      and all patients were female. The mean body mass index was 16.8 kg/m(2). The
      Howship-Romberg sign was present in only 3 patients. All patients were correctly
      diagnosed by preoperative pelvic computed tomography. All patients underwent
      operation. Operative procedures included the laparoscopic approach in 8 patients,
      the open approach in 3 patients and the inguinal approach in 2 patients. The
      hernia hilus was repaired with a simple closure in 5 patients, and with a mesh in
      8 patients. The hernia contents were small intestine in all the patients. Three
      patients underwent partial resection of the small intestine because of necrosis
      of the intestine wall. Three patients had a recurrence of the obturator hernia.
      In our present series, the patients with obturator hernia were slender females at
      an advanced age. Plevic CT was useful for the diagnosis of obturator hernia. 

PMID- 24334695
TI  - [Health system reform in the United Kingdom].
AB  - How to control the increasing health expenditures is a common problem in the
      developed countries. The main causes of this increase are ageing of the society
      and medical innovation. The UK government has introduced a market oriented health
      reform in order to balance the increasing expenditures and the quality of care.
      For example, they have introduced the GP Fundholding, Private Financial
      Initiative (PFI) for construction of public hospital, and personal budget system
      (a patient owns a budget for buying health services in the deregulated market).
      However, there is little evidence indicating the effectiveness of these programs.
      On the other hand, it is important to strengthen the labor policy in order to
      maintain the social security system. For example, programs for increasing the
      employment rate and those for increasing productivity work sharing are such
      policies. From this viewpoint, the EU countries have introduced a series of
      active employment policies, i.e., job training for unemployed persons and work
      sharing. Furthermore, as other authors report in other articles of this volume,
      the government of the UK has introduced the Fit for Work (FFW) program that
      intends to medically support workers. 

PMID- 24334696
TI  - [General background and practical implementation of Fitness for Work Statement in
      the UK].
AB  - The Statement of Fitness for Work, so called Fit Note, was introduced in the UK
      in 2010. Physicians issue Fit Note to workers when requested. The Fit Note
      provides the physician's advice about the worker's fitness for work when he or
      she has health problems, writing their advice of either "may be fit for work" or
      "not fit for work" on the form. The Fit Note also records details of the
      functional effects of workers' condition. Then the Fit Note is used to consider
      and arrange support from employers in order for workers to return to work. This
      paper reports the general background and practical implementation of Fit Note
      based on a literature review and interviews from general practitioners,
      occupational physicians, and physiotherapists in the UK. 

PMID- 24334697
TI  - [Occupational physicians' system in the United kingdom and fit note to promote
      access to occupational health services].
AB  - The Statement of Fitness for Work (Fit Note) policy was started in the UK in 2010
      in order to promote return to work after sickness absence. Fit Note is issued by
      General Practitioners (GP). We conducted an interview survey of 2 occupational
      physicians working in the UK to ascertain the impact of the introduction of Fit
      Note on occupational health in the UK. They regard the low coverage of
      occupational health services in the UK, especially among small companies and self
      employed workers, as a serious issue. Fit Note was regarded as a tool to induce
      GPs to participate in occupational health services, and it is expected that they
      will be new partners in occupational health. The English occupational physicians
      evaluated the Fit Note system highly, and believe that the increasing
      participation of GPs in occupational health services will be a steady advancement
      in occupational health in the UK. 

PMID- 24334698
TI  - [Employment-related benefit system in the UK].
AB  - Statutory Sick Pay, Jobseeker's Allowance, and Employment and Support Allowance
      are employment-related benefits in the United Kingdom (UK). They correspond to
      the Injury and Disease Allowance and Unemployment Insurance in Japan. The
      Government of the UK is determined to reform the benefit system to make it fairer
      and to improve financial work incentives, using the slogan "Welfare to Work".
      Against this background, the government of the UK united some non-contributory
      benefits into a new "Universal Credit" scheme, which started in April 2013. The
      labor policy was also reformed to improve work incentives, for example by
      abolishing the Flexible New Deal program and uniting all the "Welfare to Work"
      policies into the "Work Programme". These reforms are useful for reconsidering
      the labor and employment-related policy and benefit system of Japan. 

PMID- 24334699
TI  - [Industrial injury insurance system in the UK].
AB  - The Industrial Injuries Disablement Benefit (IIDB) is a benefit for people who
      are disabled either as a result of an accident at work or because of a prescribed
      disease. IIDB does not cover the self-employed, military personnel, or certain
      kinds of trainees. "Prescribed diseases" are defined by the Department of Work
      and Pension in a list of diseases covered by IIDB. Delivery of medical services,
      such as the medical treatment benefit in Japan, is not included in this scheme
      because most medical services are provided for in the scheme of the National
      Health Service (NHS). Prevention Projects, such as the Follow-up Medical
      Examination Benefits in Japan, are also not included. Benefits for people who
      have Pneumoconiosis (including asbestosis) are provided in the IIDB scheme. 

PMID- 24334702
TI  - Belarus: health system review.
AB  - This analysis of the Belarusian health system reviews the developments in
      organization and governance, health financing, healthcare provision, health
      reforms and health system performance since 2008. Despite considerable change
      since independence, Belarus retains a commitment to the principle of universal
      access to health care, provided free at the point of use through predominantly
      state-owned facilities, organized hierarchically on a territorial basis.
      Incremental change, rather than radical reform, has also been the hallmark of
      health-care policy, although capitation funding has been introduced in some areas
      and there have been consistent efforts to strengthen the role of primary care.
      Issues of high costs in the hospital sector and of weaknesses in public health
      demonstrate the necessity of moving forward with the reform programme. The focus
      for future reform is on strengthening preventive services and improving the
      quality and efficiency of specialist services. The key challenges in achieving
      this involve reducing excess hospital capacity, strengthening health-care
      management, use of evidence-based treatment and diagnostic procedures, and the
      development of more efficient financing mechanisms. Involving all stakeholders in
      the development of further reform planning and achieving consensus among them
      will be key to its success. 

PMID- 24334703
TI  - Down-regulation of placental mTOR, insulin/IGF-I signaling, and nutrient
      transporters in response to maternal nutrient restriction in the baboon.
AB  - The mechanisms by which maternal nutrient restriction (MNR) causes reduced fetal
      growth are poorly understood. We hypothesized that MNR inhibits placental
      mechanistic target of rapamycin (mTOR) and insulin/IGF-I signaling, down
      regulates placental nutrient transporters, and decreases fetal amino acid levels.
      Pregnant baboons were fed control (ad libitum, n=11) or an MNR diet (70% of
      controls, n=11) from gestational day (GD) 30. Placenta and umbilical blood were
      collected at GD 165. Western blot was used to determine the phosphorylation of
      proteins in the mTOR, insulin/IGF-I, ERK1/2, and GSK-3 signaling pathways in
      placental homogenates and expression of glucose transporter 1 (GLUT-1), taurine
      transporter (TAUT), sodium-dependent neutral amino acid transporter (SNAT), and
      large neutral amino acid transporter (LAT) isoforms in syncytiotrophoblast
      microvillous membranes (MVMs). MNR reduced fetal weights by 13%, lowered fetal
      plasma concentrations of essential amino acids, and decreased the phosphorylation
      of placental S6K, S6 ribosomal protein, 4E-BP1, IRS-1, Akt, ERK-1/2, and GSK-3.
      MVM protein expression of GLUT-1, TAUT, SNAT-2 and LAT-1/2 was reduced in MNR.
      This is the first study in primates exploring placental responses to maternal
      undernutrition. Inhibition of placental mTOR and insulin/IGF-I signaling
      resulting in down-regulation of placental nutrient transporters may link maternal
      undernutrition to restricted fetal growth.

PMID- 24334704
TI  - The corepressor Atrophin specifies odorant receptor expression in Drosophila.
AB  - In both insects and vertebrates, each olfactory sensory neuron (OSN) expresses
      one odorant receptor (OR) from a large genomic repertoire. How a receptor is
      specified is a tantalizing question addressing fundamental aspects of cell
      differentiation. Here, we demonstrate that the corepressor Atrophin (Atro)
      segregates OR gene expression between OSN classes in Drosophila. We show that the
      knockdown of Atro result in either loss or gain of a broad set of ORs. Each OR
      phenotypic group correlated with one of two opposing Notch fates, Notch
      responding, Nba (N(on)), and nonresponding, Nab (N(off)) OSNs. Our data show that
      Atro segregates ORs expressed in the Nba OSN classes and helps establish the Nab
      fate during OSN development. Consistent with a role in recruiting histone
      deacetylates, immunohistochemistry revealed that Atro regulates global histone 3
      acetylation (H3ac) in OSNs and requires Hdac3 to segregate OR gene expression. We
      further found that Nba OSN classes exhibit variable but higher H3ac levels than
      the Nab OSNs. Together, these data suggest that Atro determines the level of
      H3ac, which ensures correct OR gene expression within the Nba OSNs. We propose a
      mechanism by which a single corepressor can specify a large number of neuron
      classes.

PMID- 24334706
TI  - Increased dietary iron and radiation in rats promote oxidative stress, induce
      localized and systemic immune system responses, and alter colon mucosal
      environment.
AB  - Astronauts are exposed to increased body iron stores and radiation, both of which
      can cause oxidative damage leading to negative health effects. The purpose of
      this study was to investigate combined effects of high dietary iron (650 mg/kg
      diet) and radiation exposure (0.375 Gy cesium-137 every other day for 16 d) on
      markers of oxidative stress, immune system function, and colon mucosal
      environment in male Sprague-Dawley rats (n=8/group). Control rats consumed
      adequate iron (45 mg/kg diet) and were not irradiated. Combined treatments
      increased liver glutathione peroxidase, serum catalase, and colon myeloperoxidase
      while decreasing total fecal short-chain fatty acid concentrations. The high-iron
      diet alone increased leukocyte count. Radiation decreased the T-cell CD4:CD8
      ratio. Plasma iron was negatively correlated with cytokine production in
      activated monocytes. Genes involved in colon microbial signaling, immune
      response, and injury repair were altered by radiation. Genes involved with injury
      repair and pathogen recognition changed with dietary iron. These data demonstrate
      that dietary iron and radiation, alone and combined, contribute to oxidative
      stress that is related to immune system alterations in circulation and the colon.
      The model presented may help us better understand the changes to these systems
      that have been identified among astronauts.

PMID- 24334705
TI  - Hairless is a histone H3K9 demethylase.
AB  - The hairless (HR) protein contains a Jumonji C (JmjC) domain that is conserved
      among a family of proteins with histone demethylase (HDM) activity. To test
      whether HR possesses HDM activity, we performed a series of in vitro
      demethylation assays, which demonstrated that HR can demethylate monomethylated
      or dimethylated histone H3 lysine 9 (H3K9me1 or me2). Moreover, ectopic
      expression of wild-type HR, but not JmjC-mutant HR, led to pronounced
      demethylation of H3K9 in cultured human HeLa cells. We also show that two
      missense mutations in HR, which we and others described in patients with atrichia
      with papular lesions, abolished the demethylase activity of HR, demonstrating the
      role of HR demethylase activity in human disease. By ChIP-Seq analysis, we
      identified multiple new HR target genes, many of which play important roles in
      epidermal development, neural function, and transcriptional regulation,
      consistent with the predicted biological functions of HR. Our findings
      demonstrate for the first time that HR is a H3K9 demethylase that regulates
      epidermal homeostasis via direct control of its target genes.

PMID- 24334707
TI  - Vascular endothelial growth factor-a in lactobacillus casei cell wall extract
      induced coronary arteritis of a murine model.
AB  - BACKGROUND:  Vascular endothelial growth factor (VEGF) is associated with
      Kawasaki disease (KD), the most commonly acquired heart disease in developed
      countries. This study investigated the involvement of VEGF-A expression and its
      related signaling pathway in Lactobacillus casei cell wall extract (LCWE)-induced
      murine coronary artery lesions (CALs), and analyzed this in regard to the
      inhibition of CALs by spleen tyrosine kinase (Syk). METHODS AND RESULTS:  Wild
      type BALB/C mice were intraperitoneally injected with LCWE (1mg/ml) to induce
      CALs. The aortic roots, ventricular myocardium, peripheral blood leukocytes
      (PBLs), spleen, liver, kidneys, and lungs were analyzed for VEGF-A expression.
      Phosphate buffered saline (PBS)-, lipopolysaccharide (LPS)-, and zymosan-treated
      mice served as controls, and an oral Syk inhibitor served as an arteritis
      ameliorated reagent. In aortic roots and PBLs, LCWE induced an early upregulation
      and a late downregulation of VEGF-A expression. No differential VEGF-A expression
      was observed in the other organs. Most importantly, Syk inhibition significantly
      attenuated the LCWE-induced expression of VEGF-A, dimethylarginine
      dimethylaminohydrolase (DDAH)-1, and endothelial nitric oxide synthase in aortic
      roots. However, LCWE-induced aortic DDAH-2 expression remained higher, despite
      Syk inhibition. CONCLUSIONS:  Local VEGF-A and its signaling pathway are
      associated with the development of LCWE-induced CALs. Therefore, the clinical
      correlation between VEGF and human KD and the role of the VEGF-A regulation and
      signaling pathway in murine CALs warrant further investigation. 

PMID- 24334708
TI  - Multisensory representation of the space near the hand: from perception to action
      and interindividual interactions.
AB  - When interacting with objects and other people, the brain needs to locate our
      limbs and the relevant visual information surrounding them. Studies on monkeys
      showed that information from different sensory modalities converge at the single
      cell level within a set of interconnected multisensory frontoparietal areas. It
      is largely accepted that this network allows for multisensory processing of the
      space surrounding the body (peripersonal space), whose function has been linked
      to the sensory guidance of appetitive and defensive movements, and localization
      of the limbs in space. In the current review, we consider multidisciplinary
      findings about the processing of the space near the hands in humans and offer a
      convergent view of its functions and underlying neural mechanisms. We will
      suggest that evolution has provided the brain with a clever tool for representing
      visual information around the hand, which takes the hand itself as a reference
      for the coding of surrounding visual space. We will contend that the hand
      centered representation of space, known as perihand space, is a multisensory
      motor interface that allows interaction with the objects and other persons around
      us. 

PMID- 24334710
TI  - A short-lived valvular mass.

PMID- 24334709
TI  - Temporal trends in anticholinergic medication prescription in older people:
      repeated cross-sectional analysis of population prescribing data.
AB  - BACKGROUND: in older people, medications with anticholinergic (antimuscarinic)
      effects are associated with adverse clinical outcomes, the risk increasing with
      increasing anticholinergic exposure. Many anticholinergics are recognised as
      potentially inappropriate and efforts to reduce prescription have been ongoing.
      We examined temporal trends of anticholinergic prescription and exposure in older
      people. METHODS: : anonymised data on all prescribed medication dispensed to
      people >=65 years in Tayside, Scotland were obtained for the years 1995 (n =
      67,608) and 2010 (n = 73,465). The Anticholinergic Risk Scale (ARS) was adapted
      (mARS) to include newer medications and medications identified in other scales as
      having moderate to strong anticholinergic activity. An individual's mARS score
      was the sum of scores for individual medications. Differences in prescription of
      anticholinergic medications and mARS scores between 1995 and 2010 were examined.
      RESULTS: : a significantly higher proportion of older people received any
      anticholinergic medication in 2010 compared with 1995 (23.7 versus 20.7%; P <
      0.001). High anticholinergic exposure (mARS scores >=3) was seen in 7.3% in 1995
      and 9.9% in 2010 (P < 0.001). Prescription of individual anticholinergic
      medication was small-only three medications were prescribed to >2% of people. The
      risk of high anticholinergic exposure increased in those with polypharmacy,
      social deprivation, those living in care homes and women. CONCLUSION: : despite
      increasing evidence of adverse outcomes, the proportion of older people
      prescribed anticholinergic medications and the proportion with a high
      anticholinergic exposure has increased between 1995 and 2010. Prescription of
      individual drug is small so cumulative anticholinergic scores may help future
      efforts to reduce anticholinergic prescription in older people.

PMID- 24334712
TI  - Giant left atrium in a young patient with previously undetected rheumatic valve
      disease.

PMID- 24334713
TI  - Multimodality imaging reveals regurgitant jet lesion in aneurysmal anterior
      mitral leaflet: a severe complication of endocarditis.

PMID- 24334714
TI  - Renal dysfunction and heart failure: things are seldom what they seem.

PMID- 24334715
TI  - A novel type of human spontaneous coronary atherosclerosis with triglyceride
      deposition.

PMID- 24334716
TI  - Post-implantation transcatheter aortic valve migration in a left ventricular
      assist device patient with severe aortic insufficiency.

PMID- 24334717
TI  - N-terminal pro-B-type natriuretic peptide predicts cardiovascular complications
      in pregnant women with congenital heart disease.
AB  - AIMS: In women with congenital heart disease (CHD), cardiovascular complications
      during pregnancy are common, but the risk assessment of these patients remains
      difficult. This study sought to determine the independent role of N-terminal pro
      B-type natriuretic peptide (NT-proBNP) levels in addition to other parameters in
      predicting adverse cardiovascular events during pregnancy in women with CHD.
      METHODS AND RESULTS: We conducted a national, prospective multicentre cohort
      study. Follow-up with clinical evaluation and echocardiography and NT-proBNP
      measurement was performed at 20-week gestation. Adverse cardiovascular events
      occurred in 10.3% of 213 pregnancies. N-terminal pro-B-type natriuretic peptide
      levels >128 pg/mL at 20-week gestation, the presence of a mechanical valve, and
      subpulmonary ventricular dysfunction before conception were independently
      associated with events [odds ratio (OR) 10.6 (P = 0.039), OR 12.0 (P = 0.016),
      and OR 4.2 (P = 0.041), respectively]. The negative predictive value of NT-proBNP
      levels <128 pg/mL was 96.9%. N-terminal pro-B-type natriuretic peptide levels
      >128 pg/mL at 20 weeks of gestation had an additional value in predicting the
      occurrence of adverse cardiovascular events on the top of the other identified
      predictors (area under the curve 0.90 vs. 0.78, P = 0.035). CONCLUSION: Increased
      NT-proBNP levels at 20 weeks of gestation are an independent risk predictor of
      cardiovascular events during pregnancy in women with CHD.

PMID- 24334718
TI  - Diagnosis of pheochromocytoma on physical examination.

PMID- 24334711
TI  - Passive smoking and smoking cessation among patients with coronary heart disease
      across Europe: results from the EUROASPIRE III survey.
AB  - AIMS: Passive smoking is the inhalation of environmental tobacco smoke (ETS) and
      is a risk factor for coronary heart disease (CHD). We aimed to describe the
      frequency of passive smoking among patients with CHD and to investigate the
      association between ETS exposure and smoking cessation. METHODS AND RESULTS: The
      EUROASPIRE III survey was conducted in 2006-07 among CHD patients up to 80 years
      of age from 22 European regions. Patients were interviewed and examined on
      average 15 months after hospital admission for CHD. Information was obtained on
      smoking prior to hospital admission, smoking at interview, and ETS exposure at
      home, at work, and at other locations. Breath carbon monoxide was measured to
      validate self-reported non-smoking. Among 8729 patients, 6060 (69.4%) were non
      smokers prior to hospital admission, of whom 10.3% reported ETS exposure at home,
      7.2% at work, and 13.8% at other locations. Overall, 24.2% of non-smokers were
      exposed to ETS at any place. Among the 2669 patients who were smoking prior to
      hospital admission, the likelihood of cessation at interview was lower in those
      with ETS exposure at home than in those without [25.3 vs. 58.1%; adjusted odds
      ratio (OR) 0.26, 95% confidence interval (CI) 0.20-0.33]. This finding applied
      also to ETS exposure at work (32.2 vs. 52.7%; adjusted OR 0.56, 95% CI 0.42-0.76)
      and at other locations (38.0 vs. 52.8%; adjusted OR 0.63, 95% CI 0.48-0.84).
      CONCLUSION: A noteworthy proportion of non-smokers with CHD are exposed to ETS.
      Passive smoking may jeopardize smoking cessation among CHD patients.

PMID- 24334719
TI  - Fixed low-dose ultrasound-assisted catheter-directed thrombolysis for
      intermediate and high-risk pulmonary embolism.
AB  - AIMS: No standardized local thrombolysis regimen exists for the treatment of
      pulmonary embolism (PE). We retrospectively investigated efficacy and safety of
      fixed low-dose ultrasound-assisted catheter-directed thrombolysis (USAT) for
      intermediate- and high-risk PE. METHODS AND RESULTS: Fifty-two patients (65 +/-
      14 years) of whom 14 had high-risk PE (troponin positive in all) and 38
      intermediate-risk PE (troponin positive in 91%) were treated with intravenous
      unfractionated heparin and USAT using 10 mg of recombinant tissue plasminogen
      activator per device over the course of 15 h. Bilateral USAT was performed in 83%
      of patients. During 3-month follow-up, two [3.8%; 95% confidence interval (CI)
      0.5-13%] patients died (one from cardiogenic shock and one from recurrent PE).
      Major non-fatal bleeding occurred in two (3.8%; 95% CI, 0.5-13%) patients: one
      intrathoracic bleeding after cardiopulmonary resuscitation requiring transfusion,
      one intrapulmonary bleeding requiring lobectomy. Mean pulmonary artery pressure
      decreased from 37 +/- 9 mmHg at baseline to 25 +/- 8 mmHg at 15 h (P < 0.001) and
      cardiac index increased from 2.0 +/- 0.7 to 2.7 +/- 0.9 L/min/m(2) (P < 0.001).
      Echocardiographic right-to-left ventricular end-diastolic dimension ratio
      decreased from 1.42 +/- 0.21 at baseline to 1.06 +/- 0.23 at 24 h (n = 21; P <
      0.001). The greatest haemodynamic benefit from USAT was found in patients with
      high-risk PE and in those with symptom duration < 14 days. CONCLUSION: A
      standardized catheter intervention approach using fixed low-dose USAT for the
      treatment of intermediate- and high-risk PE was associated with rapid improvement
      in haemodynamic parameters and low rates of bleeding complications and mortality.

PMID- 24334720
TI  - Surgical banding of the inferior vena cava for the facilitation of transcatheter
      valve implantation in a patient with severe secondary tricuspid regurgitation.

PMID- 24334721
TI  - Surgical myectomy improves pulmonary hypertension in obstructive hypertrophic
      cardiomyopathy.
AB  - AIMS: Characterization of pulmonary hypertension (PH) and the effects of myectomy
      in hypertrophic cardiomyopathy (HCM) remain poorly defined. The aim of the study
      was to investigate the effect of myectomy on PH in HCM. METHODS AND RESULTS: This
      is a retrospective analysis of 306 consecutive symptomatic HCM patients (70% NYHA
      class III-IV) with evaluation of echocardiographic right ventricular systolic
      pressure (RVSP) both preceding (median 3 days) and following (median 4 days)
      myectomy. Compared with patients without PH (RVSP <35 mmHg, n = 145, 47%),
      patients with moderate or severe PH (RVSP >=50 mmHg, n = 51, 17%) were older,
      predominantly female, had a greater prevalence of atrial fibrillation, higher
      natriuretic peptide levels, higher left ventricular outflow tract gradient,
      higher E velocity, and larger left atria. Reduction of RVSP post-myectomy was
      evident in patients with moderate or severe PH [59 (IQR 54-71) to 50 (IQR 39-62)
      mmHg, P < 0.0001] and in all patients with PH [RVSP >= 35 mmHg, n = 161, 43 (IQR
      39-54) to 41 (IQR 35-52) mmHg, P < 0.0001]. In a subgroup of patients with long
      term data, PH continued to decline during follow-up. Clinical variables
      associated with improvement in PH in these patients were higher left atrial
      volume index (R = 0.43, P = 0.0069) and moderate or severe mitral regurgitation
      (R = 0.33, P = 0.038). CONCLUSION: Surgical myectomy is associated with
      improvement in PH, most pronounced in moderate or severe PH. These data provide
      insight into pulmonary haemodynamics following obstruction relief and can help to
      guide therapeutic expectations.

PMID- 24334722
TI  - Decrease of ERK/MAPK overactivation in prefrontal cortex reverses early memory
      deficit in a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) can be considered as a disease of memory in its initial
      clinical stages. Amyloid-beta (Abeta) peptide accumulation is central to the
      disease initiation leading later to intracellular neurofibrillary tangles (NFTs)
      of cytoskeletal tau protein formation. It is under discussion whether different
      Abeta levels of aggregation, concentration, brain area, and/or time of exposure
      might be critical to the disease progression, as well as which intracellular
      pathways it activates. The aim of the present work was to study memory-related
      early molecular and behavioral alterations in a mouse model of AD, in which a
      subtle deregulation of the physiologic function of Abeta can be inferred. For
      this purpose we used triple-transgenic (3xTg) mice, which develop Abeta and tau
      pathology resembling the disease progression in humans. Memory impairment in
      novel object recognition task was evident by 5 months of age in 3xTg mice.
      Hippocampus and prefrontal cortex extra-nuclear protein extracts developed
      differential patterns of Abeta aggregation. ERK1/MAPK showed higher levels of
      cytosolic activity at 3 months and higher levels of nuclear activity at 6 months
      in the prefrontal cortex. No significant differences were found in JNK and NF
      kappaB activity and in calcineurin protein levels. Finally, intra-PFC
      administration of a MEK inhibitor in 6-month-old 3xTg mice was able to reverse
      memory impairment, suggesting that ERK pathway alterations might at least
      partially explain memory deficits observed in this model, likely as a consequence
      of memory trace disruption. 

PMID- 24334723
TI  - Plasma amyloid-beta levels are significantly associated with a transition toward
      Alzheimer's disease as measured by cognitive decline and change in neocortical
      amyloid burden.
AB  - BACKGROUND: We evaluated the utility of longitudinal measures of plasma amyloid
      beta (Abeta) as a means to identify pre-symptomatic cognitive decline in
      Alzheimer's disease (AD) when coupled to neuroimaging and neuropsychological
      parameters. METHODS: Participants from the Australian Imaging, Biomarkers and
      Lifestyle (AIBL) study were grouped based upon cognitive change and changes in
      measurable levels of neocortical amyloid over 36 months. Participants were
      classified as those who transitioned for cognitive decline and change in
      neocortical amyloid, those healthy controls that did not transition, and stable
      AD participants over 36 months. RESULTS: Comparisons of plasma Abeta levels
      between the transition and non-transitional groups showed Abeta1-42 and the
      Abeta1-42/Abeta1-40 ratio were significantly decreased at baseline (p = 0.008 and
      p = 0.002, respectively) and at 18 months (p = 0.003 and p = 0.004,
      respectively). Both measures of neocortical amyloid and two previously published
      composite scores validated the creation of the novel transitional grouping (p <
      0.0001). In addition Abetan-42 performed well as a longitudinal prognostic
      indicator of transition toward cognitive decline, with a significant decrease in
      the transition group at the 18 month time point (p = 0.01). CONCLUSION: We
      demonstrated that baseline plasma Abeta1-42 and the Abeta1-42/Abeta1-40 ratio
      were putative biomarkers indicative of cognitive decline and validated this
      result using 18 month data. We created a novel transitional grouping and
      validated this measure using published measures of neocortical amyloid and
      composite memory scores. These findings suggest that longitudinal plasma Abeta
      could contribute to a pre-symptomatic biomarker panel for AD.

PMID- 24334725
TI  - Chemical vapor detection using nonlinear electrical properties of carbon nanotube
      bundles.
AB  - We demonstrate the electrical transport behavior of carbon nanotubes (CNTs) upon
      exposure to organic analytes (namely ethanol, benzene, acetone and toluene). The
      resulting nonlinear current-voltage characteristics revealed a power law
      dependence of the differential conductivity on the applied bias voltage.
      Moreover, suppression of differential conductivity at zero bias is found to be
      dependent on different selective analytes. The power law exponent values have
      been monitored before, during and after exposure to the chemicals, which revealed
      a reversible change in the number of electron conducting channels. Therefore, the
      reduction in the number of conductive paths can be attributed to the interaction
      of the chemical analyte on the CNT surfaces, which causes a decrease in the
      differential conductivity of the CNT sample. These results demonstrate chemical
      selectivity of CNTs due to varying electronic interaction with different chemical
      analytes. 

PMID- 24334724
TI  - Neuron-specific alterations in signal transduction pathways associated with
      Alzheimer's disease.
AB  - The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid
      deposits, intracellular neurofibrillary tangles (NFTs), and neuronal death.
      Hyperphosphorylation of tau is a key factor in the generation of NFTs. Mitogen
      activated protein kinase 1 (MAPK1) and protein kinase C beta (PRKCB) are thought
      to play a role in hyperphosphorylation, and PRCKB is thought to be involved in
      hypoxic stress and vascular dysfunction, and to trigger MAPK phosphorylation
      pathways. We performed single-cell analyses of neurons with different
      vulnerabilities to AD-related changes. Using quantitative PCR (qPCR), we measured
      the levels of MAPK1 and PRKCB transcript in CA1 (high vulnerability), CA2
      pyramidal cells from the hippocampus, granule cells from the cerebellum (low
      vulnerability), and neurons from the brain stem (nucleus tractus spinalis nervi
      trigemini, characterized by early neurophysiological deficits) at progressive
      Braak stages compared to age-matched controls. The highly vulnerable CA1
      pyramidal neurons were characterized by age- and disease-unrelated increases in
      PRCKB levels and by age- and disease-related increases in MAPK1 levels. In
      contrast, low PRKCB levels were found in CA2 pyramidal neurons, and MAPK1 levels
      were elevated in controls and intermediate AD stages. Both PRKCB and MAPK1 were
      increased in the late AD stages. MAPK1 and PRKCB levels were low in the brainstem
      and cerebellum. We propose that alterations in the expression of these two genes
      occur early in the pathogenesis of AD in a region-specific manner. In addition,
      multiple signal transduction pathways need to be affected to result in AD instead
      of physiological aging. 

PMID- 24334726
TI  - Increasing fruit and vegetable consumption and offerings to Somali children: the
      FAV-S pilot study.
AB  - OBJECTIVE: To determine the feasibility, acceptability, and impact of a parent
      centered intervention to increase fruit and vegetable servings and consumption
      among Somali children living in the United States. DESIGN: Pilot intervention
      that included Somali community health workers who organized groups of 3 or 4
      women to participate in 2 initial educational sessions, including topics of
      health and nutrition, serving size, and label reading. A third session taught
      interactive cooking to increase skills in preparing fruits and vegetables and
      increasing the numbers of vegetables included in traditional Somali dishes. The
      final session was a trip to the grocery store to identify fruits and vegetables,
      determine ripeness, and explore frozen and canned fruits and vegetables for
      halal, low-sodium, and low-sugar products. Surveys were completed pre- and post
      intervention. SETTING: Study participants were recruited from a large housing
      complex in Minneapolis, Minnesota, with a high population of Somali immigrants.
      PARTICIPANTS: Somali women (N = 25) with children aged 3 to 10 years. RESULTS:
      The intervention was feasible and well accepted. In comparing pre- and post
      intervention surveys, mothers reported providing their children significantly
      more frequent servings of fruits and vegetables at dinner, lunch, snack, and
      breakfast (vegetable only). There was a statistically significant increase in
      parent-reported intake of fruits and vegetables for themselves and their
      children. CONCLUSION: The FAV-S study was feasible and acceptable, and it
      demonstrated potential for increasing fruit and vegetable servings and
      consumption among Somali children. A larger-scale randomized trial is needed to
      assess the impact of this intervention.

PMID- 24334728
TI  - III-V nanowire arrays: growth and light interaction.
AB  - Semiconductor nanowire arrays are reproducible and rational platforms for the
      realization of high performing designs of light emitting diodes and photovoltaic
      devices. In this paper we present an overview of the growth challenges of III-V
      nanowire arrays obtained by molecular beam epitaxy and the design of III-V
      nanowire arrays on silicon for solar cells. While InAs tends to grow in a
      relatively straightforward manner on patterned (111)Si substrates, GaAs nanowires
      remain more challenging; success depends on the cleaning steps, annealing
      procedure, pattern design and mask thickness. Nanowire arrays might also be used
      for next generation solar cells. We discuss the photonic effects derived from the
      vertical configuration of nanowires standing on a substrate and how these are
      beneficial for photovoltaics. Finally, due to the special interaction of light
      with standing nanowires we also show that the Raman scattering properties of
      standing nanowires are modified. This result is important for fundamental studies
      on the structural and functional properties of nanowires. 

PMID- 24334727
TI  - MYCN is a novel oncogenic target in pediatric T-cell acute lymphoblastic
      leukemia.
AB  - MYCN is an oncogene frequently overexpressed in pediatric solid tumors whereas
      few evidences suggest his involvement in the pathogenesis of haematologic
      malignancies. Here we show that MYCN is overexpressed in a relevant proportion
      (40 to 50%) of adult and pediatric T-cell acute lymphoblastic leukemias (T-ALL).
      Focusing on pediatric T-ALL, MYCN-expressing samples were found almost
      exclusively in the TAL1-positive subgroup. Moreover, TAL1 knockdown in T-ALL cell
      lines resulted in a reduction of MYCN expression, and TAL1 directly binds to MYCN
      promoter region, suggesting that TAL1 pathway activation could sustain the up
      regulation of MYCN. The role of MYCN in T-ALL was investigated by peptide nucleic
      acid (PNA-MYCN)-mediated transcriptional silencing of MYCN and by siRNAs. MYCN
      knockdown in T-ALL cell lines resulted in a reduction of cell viability, up to
      50%, while no effect was elicited with a mismatch PNA. The inhibitory effect of
      PNA-MYCN on cell viability was due to a significant increase in apoptosis. PNA
      MYCN treatment in pediatric T-ALL samples reduced cell viability of leukemic
      cells from patients with high MYCN expression, while no effect was obtained in
      MYCN-negative blast cells. These results showed that MYCN is frequently
      overexpressed in pediatric T-ALL and suggested his role as a candidate for
      molecularly-directed therapies. 

PMID- 24334729
TI  - Results of a 2011 national questionnaire for investigation of mean glandular dose
      from mammography in Japan.
AB  - Diagnostic reference levels (DRLs) for mammography have yet to be created in
      Japan. A national questionnaire investigation into radiographic conditions in
      Japan was carried out for the purpose of creating DRLs. Items investigated
      included the following: tube voltage; tube current; current-time product; source
      image distance; craniocaudal view; automatic exposure control (AEC) settings;
      name of mammography unit; image receptor system (computed radiography (CR), flat
      panel detector (FPD), or film/screen (F/S)); and supported or unsupported monitor
      diagnosis (including monitor resolution). Estimation of the mean glandular dose
      (MGD) for mammography was performed and compared with previous investigations.
      The MGD was 1.58(0.48) mGy, which did not significantly differ from a 2007
      investigation. In relation to image receptors, although no difference in average
      MGD values was observed between CR and FPD systems, F/S systems had a
      significantly decreased value compared to both CR and FPDs. Concerning digital
      systems (FPDs), the MGD value of the direct conversion system was significantly
      higher than the indirect conversion system. No significant difference in MGD
      value was evident concerning type of monitor diagnosis for either the CR or the
      FPD digital systems; however, hard copies were used more often in CR. No
      significant difference in the MGD value was found in relation to monitor
      resolution. This report suggests ways to lower the doses patients undergoing
      mammography receive in Japan, and serves as reference data for 4.2 cm compressed
      breast tissue of 50% composition DRLs. Furthermore, our findings suggest that
      further optimisation of FPD settings can promote a reduction in the MGD value. 

PMID- 24334730
TI  - Estonia: health system review.
AB  - This analysis of the Estonian health system reviews recent developments in
      organization and governance, health financing, health-care provision, health
      reforms and health system performance. Without doubt, the main issue has been the
      2008 financial crisis. Although Estonia has managed the downturn quite
      successfully and overall satisfaction with the system remains high, it is hard to
      predict the longer-term effects of the austerity package. The latter included
      some cuts in benefits and prices, increased cost sharing for certain services,
      extended waiting times, and a reduction in specialized care. In terms of health
      outcomes, important progress was made in life expectancy, which is nearing the
      European Union (EU) average, and infant mortality. Improvements are necessary in
      smoking and alcohol consumption, which are linked to the majority of avoidable
      diseases. Although the health behaviour of the population is improving, large
      disparities between groups exist and obesity rates, particularly among young
      people, are increasing. In health care, the burden of out-of-pocket payments is
      still distributed towards vulnerable groups. Furthermore, the number of
      hospitals, hospital beds and average length of stay has decreased to the EU
      average level, yet bed occupancy rates are still below EU averages and efficiency
      advances could be made. Going forwards, a number of pre-crisis challenges remain.
      These include ensuring sustainability of health care financing, guaranteeing a
      sufficient level of human resources, prioritizing patient-centred health care,
      integrating health and social care services, implementing intersectoral action to
      promote healthy behaviour, safeguarding access to health care for lower
      socioeconomic groups, and, lastly, improving evaluation and monitoring tools
      across the health system. 

PMID- 24334731
TI  - Species richness and the temporal stability of biomass production: a new analysis
      of recent biodiversity experiments.
AB  - The relationship between biological diversity and ecological stability has
      fascinated ecologists for decades. Determining the generality of this
      relationship, and discovering the mechanisms that underlie it, are vitally
      important for ecosystem management. Here, we investigate how species richness
      affects the temporal stability of biomass production by reanalyzing 27 recent
      biodiversity experiments conducted with primary producers. We find that, in
      grasslands, increasing species richness stabilizes whole-community biomass but
      destabilizes the dynamics of constituent populations. Community biomass is
      stabilized because species richness impacts mean biomass more strongly than its
      variance. In algal communities, species richness has a minimal effect on
      community stability because richness affects the mean and variance of biomass
      nearly equally. Using a new measure of synchrony among species, we find that for
      both grasslands and algae, temporal correlations in species biomass are lower
      when species are grown together in polyculture than when grown alone in
      monoculture. These results suggest that interspecific interactions tend to
      stabilize community biomass in diverse communities. Contrary to prevailing
      theory, we found no evidence that species' responses to environmental variation
      in monoculture predicted the strength of diversity's stabilizing effect.
      Together, these results deepen our understanding of when and why increasing
      species richness stabilizes community biomass.

PMID- 24334732
TI  - Complex interaction of dendritic connectivity and hierarchical patch size on
      biodiversity in river-like landscapes.
AB  - Habitat fragmentation and land use changes are causing major biodiversity losses.
      Connectivity of the landscape or environmental conditions alone can shape
      biodiversity patterns. In nature, however, local habitat characteristics are
      often intrinsically linked to a specific connectivity. Such a link is evident in
      riverine ecosystems, where hierarchical dendritic structures command related
      scaling on habitat capacity. We experimentally disentangled the effect of local
      habitat capacity (i.e., the patch size) and dendritic connectivity on
      biodiversity in aquatic microcosm metacommunities by suitably arranging patch
      sizes within river-like networks. Overall, more connected communities that occupy
      a central position in the network exhibited higher species richness, irrespective
      of patch size arrangement. High regional evenness in community composition was
      found only in landscapes preserving geomorphological scaling properties of patch
      sizes. In these landscapes, some of the rarer species sustained regionally more
      abundant populations better tracking their own niche requirements compared to
      landscapes with homogeneous patch size or landscapes with spatially uncorrelated
      patch size. Our analysis suggests that altering the natural link between
      dendritic connectivity and patch size strongly affects community composition and
      population persistence at multiple scales. The experimental results are
      demonstrating a principle that can be tested in theoretical metacommunity models
      and eventually be projected to real riverine ecosystems.

PMID- 24334733
TI  - Mutualistic mimicry and filtering by altitude shape the structure of Andean
      butterfly communities.
AB  - Both the abiotic environment and abiotic interactions among species contribute to
      shaping species assemblages. While the roles of habitat filtering and competitive
      interactions are clearly established, less is known about how positive
      interactions, whereby species benefit from the presence of one another, affect
      community structure. Here we assess the importance of positive interactions by
      studying Andean communities of butterflies that interact mutualistically via
      Mullerian mimicry. We show that communities at similar altitudes have a similar
      phylogenetic composition, confirming that filtering by altitude is an important
      process. We also provide evidence that species that interact mutualistically
      (i.e., species that share the same mimicry wing pattern) coexist at large scales
      more often than expected by chance. Furthermore, we detect an association between
      mimicry structure and altitude that is stronger than expected even when phylogeny
      is corrected for, indicating adaptive convergence for wing pattern and/or
      altitudinal range driven by mutualistic interactions. Positive interactions
      extend far beyond Mullerian mimicry, with many examples in plants and animals,
      and their role in the evolution and assembly of communities may be more pervasive
      than is currently appreciated. Our findings have strong implications for the
      evolution and resilience of community structure in a changing world.

PMID- 24334734
TI  - Phenological and geographical shifts have interactive effects on migratory bird
      populations.
AB  - For many taxa, ranges are shifting toward the poles and the timing of seasonal
      reproduction is advancing in response to climate change. For migratory birds,
      changes such as these could produce particularly strong impacts because of their
      potential to affect migratory timing and distance. Due to the relatively complex
      life histories of migratory species, however, it is difficult to intuit exactly
      what these impacts will be. Here, we develop a general population model for a
      long-distance migrant, introducing a framework for understanding the potential
      implications of changes in both phenology and migratory distance for bird
      abundances. We find that population sizes may increase with either shorter or
      longer migratory distances, depending on the nature of any concurrent
      phenological changes. This interaction between timing and distance suggests a
      need to consider multiple potential responses to climate change simultaneously in
      order to understand the overall impact of climate change on migratory
      populations. Our results reveal a degree of variability in the qualitative nature
      of this phenology-distance interaction, suggesting a possible explanation for
      observed variation in how migratory birds have already responded to climate
      change.

PMID- 24334735
TI  - Extrapair paternity rates vary with latitude and elevation in emberizid sparrows.
AB  - Mating systems can vary among species and populations and thus influence
      evolutionary trajectories, ecological traits, and population demography. The
      siring of offspring by an extrapair male, or extrapair paternity (EPP), is a
      widespread and varied phenomenon in all vertebrate classes. However, we do not
      understand all of the factors associated with variation in EPP rates. The
      breeding synchrony hypothesis suggests that EPP rates should increase with
      latitude and elevation, whereas the paternal care hypothesis predicts that EPP
      rates should decrease with elevation. To address these hypotheses, we
      investigated how population EPP rates vary over elevation and latitude in
      emberizid sparrows. In comparative analyses including the effects of phylogeny,
      the relationship between EPP rates and elevation depended on latitude. EPP rates
      were greater in higher-latitude populations. But within higher-latitude
      populations, EPP rates decreased with increasing elevation. These findings
      provide support for both the breeding synchrony and paternal care hypotheses,
      suggesting that in lower-latitude, higher-elevation populations, the need for
      male parental care does not outweigh the benefits of seeking extrapair
      fertilizations in populations with relatively synchronous breeding. In contrast,
      at higher-latitude, higher-elevation sites, the need for male parental care is
      greater and might drive lower rates of extrapair mating despite highly
      synchronous breeding.

PMID- 24334736
TI  - Intralocus sexual conflict over wing length in a wild migratory bird.
AB  - Intralocus sexual conflict (ISC) occurs when males and females have different
      adaptive peaks but are constrained from evolving sexual dimorphism because of
      shared genes. Implications of this conflict on evolutionary dynamics in wild
      populations have not been investigated in detail. In comprehensive analyses of
      selection, heritability, and genetic correlations, we found evidence for an ISC
      over wing length, a key trait for flight performance and migration, in a long
      term study of wild great reed warblers (Acrocephalus arundinaceus). We found
      moderate sexual dimorphism, high heritability, moderate sexually antagonistic
      selection, and strong positive cross-sex genetic correlation in wing length,
      together supporting the presence of ISC. A negative genetic correlation between
      male wing length and female fitness indicated that females inheriting alleles for
      longer wings from their male relatives also inherited lower fitness. Moreover,
      cross-sex genetic correlations imposed constraint on the predicted
      microevolutionary trajectory of wing length (based on selection gradients),
      especially in females where the predicted response was reversed. The degree of
      sexual dimorphism in wing length did not change over time, suggesting no sign of
      conflict resolution. Our study provides novel insight into how an ISC over a
      fitness trait can affect microevolution in a wild population under natural
      selection.

PMID- 24334737
TI  - Testing the aerobic model for the evolution of endothermy: implications of using
      present correlations to infer past evolution.
AB  - The evolution of endothermy is one of the most puzzling events in vertebrate
      evolution, for which several hypotheses have been proposed. The most accepted
      model is the aerobic model, which assumes the existence of a genetic correlation
      between resting metabolic rate (RMR) and maximum aerobic capacity (whose standard
      measure is maximum metabolic rate, MMR). This model posits that directional
      selection acted on maximum aerobic capacity and resting metabolic rate increased
      as a correlated response, in turn increasing body temperature. To test this
      hypothesis we implemented a simple two-trait quantitative genetic model in which
      RMR and MMR are initially independent of each other and subject to stabilizing
      selection to two separate optima. We show mutations that arise that affect both
      traits can lead to the evolution of a genetic correlation between the traits
      without any significant shifting of the two trait means. Thus, the presence of a
      genetic correlation between RMR and MMR in living animals provides no support in
      and of itself for the past elevation of metabolic rate via selection on aerobic
      capacity. This result calls into question the testability of the hypothesis that
      RMR increased as a correlated response to directional selection on MMR, in turn
      increasing body temperature, using quantitative genetics. Given the difficulty in
      studying ancient physiological processes, we suggest that approaches such as this
      model are a valuable alternative for analyzing possible mechanisms of endothermy
      evolution.

PMID- 24334738
TI  - Caste load and the evolution of reproductive skew.
AB  - Reproductive skew theory seeks to explain how reproduction is divided among group
      members in animal societies. Existing theory is framed almost entirely in terms
      of selection, though nonadaptive processes must also play some role in the
      evolution of reproductive skew. Here I propose that a genetic correlation between
      helper fecundity and breeder fecundity may frequently constrain the evolution of
      reproductive skew. This constraint is part of a wider phenomenon that I term
      "caste load," which is defined as the decline in mean fitness caused by caste
      specific selection pressures, that is, differential selection on breeding and
      nonbreeding individuals. I elaborate the caste load hypothesis using quantitative
      and population genetic arguments and individual-based simulations. Although
      selection can sometimes erode genetic correlations and resolve caste load, this
      may be constrained when mutations have similar pleiotropic effects on breeder and
      helper traits. I document evidence for caste load, identify putative genomic
      adaptations to it, and suggest future research directions. The models highlight
      the value of considering adaptation within the boundaries imposed by genetic
      architecture and incidentally reaffirm that monogamy promotes the evolutionary
      transition to eusociality.

PMID- 24334739
TI  - Driven apart: the evolution of ploidy differences between the sexes under
      antagonistic selection.
AB  - Sexual reproduction in eukaryotes implies a biphasic life cycle with alternating
      haploid and diploid phases. The nature of the biphasic life cycle varies markedly
      across taxa, and often either the diploid or the haploid phase is predominant.
      Why some taxa spend a major part of their life cycle as diploids and others as
      haploids remains a conundrum. Furthermore, ploidy levels may not only vary across
      life cycle phases but may also differ between males and females. The existence of
      two life cycle phases and two sexes bears a high potential for antagonistic
      selection, which in turn may influence the evolution of ploidy levels. We
      explored the evolution of ploidy levels when selection depends on both ploidy and
      sex. Our analyses show that antagonistic selection may drive the ploidy levels
      between males and females apart. In a subsequent step, we explicitly explored the
      evolution of arrhenotoky (i.e., haploid males and diploid females) in the context
      of antagonistic selection. Our model shows that selection on arrhenotoky depends
      on male fitness but evolves regardless of the fitness consequences to females.
      Overall we provide a plausible explanation for the evolution of sex differences
      in ploidy levels, a principle that can be extended to any system with asymmetric
      inheritance.

PMID- 24334740
TI  - The evolution of age-dependent plasticity.
AB  - When organisms encounter environments that are heterogeneous in time, phenotypic
      plasticity is often favored by selection. The degree of such plasticity can vary
      during an organism's lifetime, but the factors promoting differential plastic
      responses at different ages or life stages remain poorly understood. Here we
      develop and analyze an evolutionary model to investigate how environmental
      information is optimally collected and translated into phenotypic adjustments at
      different ages. We demonstrate that plasticity must often be expected to vary
      with age in a nonmonotonic fashion. Early in life, it is generally optimal to
      delay phenotypic adjustments until sufficient information has been collected
      about the state of the environment to warrant a costly phenotypic adjustment.
      Toward the end of life, phenotypic adjustments are disfavored as well because
      their beneficial effects can no longer be fully reaped before death. Our analysis
      clarifies how patterns of age-dependent plasticity are shaped by the interplay of
      environmental uncertainty, the accuracy of perceived information, and the costs
      of phenotypic adjustments with life-history determinants such as the relative
      strengths of fecundity and viability selection experienced by the organism over
      its lifetime. We conclude by comparing our results with expectations for
      alternative mechanisms, including developmental constraints, that promote age
      dependent plasticity.

PMID- 24334741
TI  - Pollinator deception in the orchid mantis.
AB  - Mimicry has evolved in contexts such as camouflage, predator deterrence, luring
      of prey, and pollinator attraction. Mimicry of flowers has until now been
      demonstrated only in angiosperms, yet it has been hypothesized that the Malaysian
      orchid mantis Hymenopus coronatus mimics a flower to attract pollinators as prey.
      Despite the popularity of this charismatic insect, this long-discussed hypothesis
      has never been experimentally investigated. We found that, as predicted for
      mimicry, the color of H. coronatus is indistinguishable from the color of
      sympatric flowers for hymenopteran pollinators. Field experiments show that
      isolated mantises attract wild pollinators at a rate even higher than flowers and
      capture these pollinators as prey items. After more than a century of conjecture,
      we provide the first experimental evidence of pollinator deception in the orchid
      mantis and the first description of a unique predatory strategy that has not been
      documented in any other animal species.

PMID- 24334742
TI  - Ants and ant scent reduce bumblebee pollination of artificial flowers.
AB  - Ants on flowers can disrupt pollination by consuming rewards or harassing
      pollinators, but it is difficult to disentangle the effects of these exploitative
      and interference forms of competition on pollinator behavior. Using highly
      rewarding and quickly replenishing artificial flowers that simulate male or
      female function, we allowed bumblebees (Bombus impatiens) to forage (1) on
      flowers with or without ants (Myrmica rubra) and (2) on flowers with or without
      ant scent cues. Bumblebees transferred significantly more pollen analogue both to
      and from ant-free flowers, demonstrating that interference competition with ants
      is sufficient to modify pollinator foraging behavior. Bees also removed
      significantly less pollen analogue from ant-scented flowers than from controls,
      making this the first study to show that bees can use ant scent to avoid
      harassment at flowers. Ant effects on pollinator behavior, possibly in addition
      to their effects on pollen viability, may contribute to the evolution of floral
      traits minimizing ant visitation.

PMID- 24334743
TI  - Sex-chromosome turnovers: the hot-potato model.
AB  - Sex-determining systems often undergo high rates of turnover but for reasons that
      remain largely obscure. Two recent evolutionary models assign key roles,
      respectively, to sex-antagonistic (SA) mutations occurring on autosomes and to
      deleterious mutations accumulating on sex chromosomes. These two models capture
      essential but distinct key features of sex-chromosome evolution; accordingly,
      they make different predictions and present distinct limitations. Here we show
      that a combination of features from the two models has the potential to generate
      endless cycles of sex-chromosome transitions: SA alleles accruing on a chromosome
      after it has been co-opted for sex induce an arrest of recombination; the ensuing
      accumulation of deleterious mutations will soon make a new transition
      ineluctable. The dynamics generated by these interactions share several important
      features with empirical data, namely, (i) that patterns of heterogamety tend to
      be conserved during transitions and (ii) that autosomes are not recruited
      randomly, with some chromosome pairs more likely than others to be co-opted for
      sex.

PMID- 24334744
TI  - The cold-water connection: Bergmann's rule in North American freshwater fishes.
AB  - Understanding general rules governing macroecological body size variations is one
      of the oldest pursuits in ecology. However, this science has been dominated by
      studies of terrestrial vertebrates, spurring debate over the validity of such
      rules in other taxonomic groups. Here, relationships between maximum body size
      and latitude, temperature, and elevation were evaluated for 29 North American
      freshwater fish species. Bergmann's rule (i.e., that body size correlates
      positively with latitude and negatively with temperature) was observed in 38% of
      species, converse Bergmann's rule (that body size correlates negatively with
      latitude and positively with temperature) was observed in 34% of species, and 28%
      of species showed no macroecological body size relationships. Most notably, every
      species that expressed Bergmann's rule was a cool- or cold-water species while
      every species that expressed converse Bergmann's rule was a warm-water species,
      highlighting how these patterns are likely connected to species thermal niches.
      This study contradicts previous research suggesting Bergmann's rule does not
      apply to freshwater fishes, and is congruent with an emerging paradigm of
      variable macroecological body size patterns in poikilotherms.

PMID- 24334745
TI  - Keystone and intraguild predation, intraspecific density dependence, and a guild
      of coexisting consumers.
AB  - Previous models of diamond-shaped and intraguild predation community modules have
      represented the essence of the trade-off necessary for a top predator to prevent
      competitive exclusion among a set of resource-limited consumers. However, at most
      two consumers can coexist in these models. In this article, I show how
      intraspecific density dependence in the consumers can permit many more than two
      consumers to coexist in these community modules. Moreover, responses of the
      community to removal of the top predator depend on the patterns of the strengths
      of species interactions relative to the strengths of intraspecific density
      dependence. If the consumers experience similar strengths of intraspecific
      density dependence, removing the top predator will in most cases have little
      effect on consumer species richness. A substantial reduction in consumer species
      richness with predator removal (i.e., the keystone predation effect) will
      typically occur only when the consumer that can support a population at the
      lowest resource abundance also (1) experiences substantially weaker intraspecific
      density dependence than other consumers and (2) experiences significantly higher
      levels of mortality from the predator. These results identify how intraspecific
      density dependence fosters the coexistence of multiple consumers in two important
      community modules and shapes the responses of these community modules to
      perturbations such as predator removal.

PMID- 24334746
TI  - Evolutionary rescue in structured populations.
AB  - Environmental change, if severe, can drive a population extinct unless the
      population succeeds in adapting to the new conditions. How likely is a population
      to win the race between population decline and adaptive evolution? Assuming that
      environmental degradation progresses across a habitat, we analyze the impact of
      several ecological factors on the probability of evolutionary rescue.
      Specifically, we study the influence of population structure and density
      dependent competition as well as the speed and severity of environmental change.
      We also determine the relative contribution of standing genetic variation and new
      mutations to evolutionary rescue. To describe population structure, we use a
      generalized island model, where islands are affected by environmental
      deterioration one after the other. Our analysis is based on the mathematical
      theory of time-inhomogeneous branching processes and complemented by computer
      simulations. We find that in the interplay of various, partially antagonistic
      effects, the probability of evolutionary rescue can show nontrivial and
      unexpected dependence on ecological characteristics. In particular, we generally
      observe a nonmonotonic dependence on the migration rate between islands.
      Counterintuitively, under some circumstances, evolutionary rescue can occur more
      readily in the face of harsher environmental shifts, because of the reduced
      competition experienced by mutant individuals. Similarly, rescue sometimes occurs
      more readily when the entire habitat degrades rapidly, rather than progressively
      over time, particularly when migration is high and competition strong.

PMID- 24334748
TI  - Natural selection, coevolution, and the web of life.

PMID- 24334750
TI  - New horizons in care home medicine.
AB  - Care home medicine has been an under-researched area, but over the last decade
      there has been a substantial growth in publications. Most of these have focused
      on the 'geriatric giants' of falls, incontinence and mental health issues
      (especially dementia, behavioural disturbance and depression) as well as other
      key topics such as medication use and issues related to death and dying. Other
      areas of recent interest are around access to health services for care home
      residents, how such services may most effectively be developed and how the
      quality of life for residents can be enhanced. While many of the reported studies
      are small and not always well designed, evidence in several areas is emerging
      which begins to guide service developments. A common theme is that multi
      disciplinary interventions are the most effective models of delivery. The role of
      care home staff as members of these teams is key to their effectiveness. Recent
      consensus guidelines around falls prevention in care homes synthesise the
      evidence and recommend multi-disciplinary interventions, and clarify the role of
      vitamin D and of exercise in certain populations in the care home. The benefits
      of pharmacist led medication reviews are beginning to emerge; although studies
      reviewed to date have not yet led to the 'holy grail' of hospital admission
      avoidance they point to benefits in reduction of drug burden. Effectiveness may
      be enhanced when working with GPs and care home nurses. Welcome evidence is
      emerging that in the UK the rate of prescription of anti-psychotics has fallen.
      This is clear evidence that changes in practice around care homes can be
      effected. The poor access to non-pharmacological therapies for care home
      residents with behavioural disturbance remains a significant gap in service. End
      of-life care planning and delivery is an important part of care in care homes,
      and there is evidence that integrated pathways can improve care; however, the use
      of palliative care medications was limited unless specialist care staff were
      involved. Integrated models of care that focus on resident-centred goals and
      which value the role of care home staff as members of the team working to deliver
      these goals are most likely to result in improvements in the quality of care
      experienced by care home residents. 

PMID- 24334751
TI  - Where will genetic toxicology testing be in 30 years' time? Summary report of the
      25th Industrial Genotoxicity Group Meeting, Royal Society of Medicine, London,
      November 9, 2011.
AB  - A number of influences including legislation, industry and academia have
      encouraged advances in computational toxicology and high-throughput testing to
      probe more broadly putative toxicity pathways. The aim of the 25th United Kingdom
      Mutagen Society (UKEMS) Industrial Genotoxicity Group Annual Meeting 2011 was to
      explore current and upcoming research tools that may provide new cancer risk
      estimation approaches and discuss the genotoxicity testing paradigm of the
      future. The meeting considered whether computer modelling, molecular biology
      systems and/or adverse outcome pathway approaches can provide more accurate
      toxicity predictions and whether high-content study data, pluripotent stem cells
      or new scientific disciplines, such as epigenetics and adductomics, could be
      integrated into the risk assessment process. With close collaboration between
      industry, academia and regulators next generation predictive models and high
      content tools have the potential to transform genetic toxicology testing in the
      21st century. 

PMID- 24334752
TI  - Distribution of bone mineral content is associated with body weight and exercise
      capacity in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Although low bone mineral density is highly prevalent in patients
      with chronic obstructive pulmonary disease (COPD), the distribution of the
      reduced bone mass has not been fully elucidated. OBJECTIVES: To determine
      regional bone mass loss in patients with COPD and investigate whether the change
      in distribution may be associated with body weight loss and functional capacity.
      METHODS: Body mass index (BMI) was assessed, and height squared indices were
      derived for the bone mineral content index (BMCI) of the arms, legs and trunk by
      dual-energy X-ray absorptiometry in 45 male patients with COPD and 12 age- and
      sex-matched control subjects. Pulmonary function tests were performed, and
      maximal oxygen uptake (VO2max) was measured. RESULTS: The BMCI was lower in the
      total bone, legs and trunk of patients with COPD than in control subjects,
      although the BMCI in the arms was similar between the groups. BMI correlated
      significantly with the BMCI in all 3 segments. Bone mineral content (BMC) in the
      trunk, expressed as a percentage of total BMC (BMC trunk/total BMC), correlated
      significantly with BMI. The BMCI in the trunk was closely related with VO2max but
      not with airflow limitation. CONCLUSIONS: There was a regional difference in BMC
      reduction, but a predominant reduction of bone mass in the trunk was not
      associated with the severity of airflow limitation but rather with body weight
      loss and exercise intolerance. These data suggest that body weight loss and
      exercise intolerance are important risk factors for vertebral fracture in
      patients with COPD.

PMID- 24334756
TI  - Living an everyday life through a child's cancer trajectory: families' lived
      experiences 7 years after diagnosis.
AB  - The aim of this study was to illuminate the lived experiences of families where a
      child had survived 7 years from a diagnosis of childhood cancer. This article
      describes one part of an inductive and longitudinal research project that
      included 17 families. Four families whose child was diagnosed with cancer 7 years
      previously were interviewed using a hermeneutical phenomenological approach. The
      families lived experience was described in one essential theme, "Living an
      everyday life through the child's cancer trajectory," further illuminated in 3
      related themes: "Leaving the disease behind yet feeling its presence," "Being the
      same yet always different," and "Feeling stronger yet vulnerable." The results
      suggest that family members feel vulnerable even if a long period of time has
      passed since completion of treatment. To varied degrees they still may need
      support. When moving forward in life, the family members are helped if they can
      reconcile their memories and experiences derived from the childhood cancer
      trajectory. 

PMID- 24334758
TI  - All-solution-processed nonvolatile flexible nano-floating gate memory devices.
AB  - Organic semiconductors have great potential for future electronic applications
      owing to their inherent flexibility, low cost, light weight and ability to easily
      cover large areas. However, all of these advantageous material properties can
      only be harnessed if simple, cheap and low-temperature fabrication processes,
      which exclude the need for vacuum deposition and are compatible with flexible
      plastic substrates, are employed. There are a few solution-based techniques such
      as spin-coating and inkjet printing that meet the above criteria. In this paper,
      we describe a novel all-solution-processed nonvolatile memory device fabricated
      on a flexible plastic substrate. The source, drain and gate electrodes were
      printed using an inkjet printer with a conducting organic solution, while the
      semiconducting layer was spin-coated with an n-type polymer. The charge-trapping
      layer was composed of spin-coated reduced graphene oxide (rGO), which was
      prepared in the form of a solution using Hummer's method. The fabricated device
      was characterized in order to confirm the memory characteristics. Device
      parameters such as threshold voltage shift, retention/endurance characteristics,
      mechanical robustness and reliability upon bending were also analyzed. 

PMID- 24334757
TI  - Cross-sectional study: CagA-positive Helicobacter pylori infection, acute
      coronary artery disease and systemic levels of B-type natriuretic peptide.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) determination is routinely used to
      evaluate the severity of congestive heart failure, a possible consequence of
      coronary artery disease (CAD). CAD originates from vascular atherosclerotic
      processes and is stimulated by inflammatory events, which may also be triggered
      by chronic bacterial infections. AIM: To explore the effect of Helicobacter
      pylori infection upon systemic BNP, tumour necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) levels and linear homology between cardiac peptides and H
      pylori. METHODS: A group of 103 consecutive patients with a diagnosis of non-ST
      elevation acute CAD (ACAD) and no other concomitant pathology was examined. BNP
      was measured by a commercial solid-phase sandwich immunoradiometric assay. H
      pylori infection, CagA serological status and circulating levels of IL-6 and TNF
      alpha, were determined by ELISA assays. Amino acid sequence homology between
      human cardiac and H pylori peptides was investigated by Basic Local Alignment
      Search Tool (BLAST) analysis. RESULTS: Circulating levels of BNP and IL-6, in
      pg/mL (interquartile difference), among infected patients with anti-CagA serum
      antibodies, respectively 781 (1899) and 37.7 (137.6), were significantly
      increased in respect to those measured in uninfected patients, respectively 325
      (655) and 7.7 (23.5), (p<0.01 and p=0.025), and, with regard to BNP alone, also
      in patients infected by CagA negative H pylori strains, 305 (593), (p<0.01). TNF
      alpha levels were raised in CagA positive in respect to uninfected patients.
      Tropomyosin and Ca2+ transporting ATPases showed strong similarities to H pylori
      proteins, suggesting the existence of molecular mimicry phenomena. CONCLUSIONS:
      Chronic infection by H pylori expressing CagA correlates with high circulating
      levels of BNP and IL-6 in patients with ACAD.

PMID- 24334759
TI  - Genetic subclonal complexity and miR125a-5p down-regulation identify a subset of
      patients with inferior outcome in low-risk CLL patients.
AB  - The majority of patients with chronic lymphocytic leukemia (CLL) and favorable
      prognostic features live for long periods without treatment. However, unexpected
      disease progression is observed in some cases. In a cohort of untreated CD38- CLL
      patients with normal FISH or isolated 13q- we found that, by fluorescence in situ
      hybridization (FISH), 16/28 cases presented, within immunomagnetic sorted CD38+
      cells, genetic lesions undetectable in the CD38- fraction. These patients showed
      a shorter time to first treatment (TTFT, p=0.0162) in comparison to cases without
      FISH lesions in CD38+ cells. Patients with FISH abnormalities in CD38+ cells
      showed a distinctive microRNA profile, characterized by the down-regulation of
      miR-125a-5p both in the CD38- and CD38+ populations. In an independent cohort of
      71 consecutive untreated CD38- CLL with normal FISH or isolated 13q-, a lower
      miR125a-5p expression was associated with a shorter TTFT both in univariate and
      multivariate analysis (p=0.003 and 0.016, respectively) and with a higher
      prevalence of mutations (7/12 vs 0/8, p=0.015) as assessed by next-generation
      sequencing. In conclusion, our data showed previously unrecognized subclonal
      heterogeneity within the CD38+ fraction of CD38- CLL patients with low-risk FISH
      findings and suggested an association between down-regulated miR-125a-5p
      expression, genetic complexity and worse outcome. 

PMID- 24334760
TI  - Colonization of the human gut by E. coli and colorectal cancer risk.
AB  - PURPOSE: The intestinal microbiota is potentially involved in the development of
      colorectal carcinoma via various mechanisms. Escherichia coli are commensal
      bacteria of the human gut microbiota, but some pathogenic strains have acquired
      the ability to induce chronic inflammation and/or produce toxins, such as
      cyclomodulin, which could participate in the carcinogenesis process. Here, we
      analyzed the E. coli population associated with mucosa of patients with colon
      cancer in relation to clinicopathologic characteristics. We assessed carcinogenic
      properties of a colon cancer-associated E. coli strain in multiple intestinal
      neoplasia (Min) mice. EXPERIMENTAL DESIGN: Mucosa-associated or internalized E.
      coli were quantified and characterized from tumors and mucosa of patients with
      colon cancer and the healthy mucosa of diverticulosis controls. Min mice were
      inoculated with a colon cancer-associated E. coli strain (11G5). The number of
      colonic polyps was evaluated at 7 weeks after infection. RESULTS: An increased
      level of mucosa-associated and internalized E. coli was observed in the tumors
      compared with normal tissue. A relationship between poor prognostic factors for
      colon cancer (tumor-node-metastasis stage) and colonization of mucosa by E. coli
      was observed. Pathogenic cyclomodulin-positive E. coli strains were more
      prevalent on mucosa of patients with stages III/IV than those with stage I colon
      cancer. Proliferative index and E. coli colonization level of the mucosa distant
      from the tumor significantly correlated. Min mice infected with the E. coli
      strain 11G5 displayed a marked increase in the number of visible colonic polyps
      compared with controls. CONCLUSION: These findings support that pathogenic E.
      coli could be a cofactor in pathogenesis of colorectal cancer.

PMID- 24334761
TI  - Mesothelin overexpression is a marker of tumor aggressiveness and is associated
      with reduced recurrence-free and overall survival in early-stage lung
      adenocarcinoma.
AB  - PURPOSE: In an effort to identify molecular markers of tumor aggressiveness and
      therapeutic targets in lung adenocarcinoma (ADC), we investigated the expression
      of mesothelin (MSLN) in lung ADC, as well as its biologic and clinical relevance.
      EXPERIMENTAL DESIGN: In a training and validation set of patients with early
      stage (I-III) lung ADC (n = 1,209), a tissue microarray consisting of tumors and
      normal lung tissue was used to examine the association between MSLN expression
      and recurrence-free survival (RFS) and overall survival (OS). The influence of
      MSLN overexpression on lung ADC was investigated in vitro and in vivo by use of
      clinically relevant orthotopic and metastatic xenogeneic and syngeneic mouse
      models. RESULTS: MSLN was expressed in 69% of lung ADC tumors, with one in five
      patients strongly expressing MSLN and no expression in normal lung tissue.
      Increased MSLN expression was associated with reduced OS [HR = 1.78; 95%
      confidence interval (CI), 1.26-2.50; P < 0.01] and RFS (HR = 1.67; 95% CI, 1.21
      2.27; P < 0.01) in multivariate analyses, even after adjustment for currently
      known markers of tumor aggressiveness in lung ADC: male sex, smoking history,
      increasing stage, morphologic pattern, visceral pleural invasion, lymphatic or
      vascular invasion, and mutation status. In vitro, lung ADC cells overexpressing
      MSLN demonstrated increased cell proliferation, migration, and invasion; in vivo,
      mice with MSLN(+) tumors demonstrated decreased survival (P = 0.001).
      CONCLUSIONS: MSLN expression in patients with early-stage lung ADC is associated
      with increased risk of recurrence and reduced OS, indicating that MSLN expression
      is a molecular marker of tumor aggressiveness and a potential target for therapy.

PMID- 24334763
TI  - DNA methyltransferase inhibition reverses epigenetically embedded phenotypes in
      lung cancer preferentially affecting polycomb target genes.
AB  - PURPOSE: Cancer cell phenotypes are partially determined by epigenetic
      specifications, such as DNA methylation. Metastasis development is a late event
      in cancerogenesis and might be associated with epigenetic alterations.
      EXPERIMENTAL DESIGN: An in vivo selection approach was used to generate highly
      aggressive non-small cell lung cancer (NSCLC) cell lines (A549 and HTB56)
      followed by genome-wide DNA methylation analysis. Furthermore, the therapeutic
      effects of the epigenetic agent azacytidine on DNA methylation patterns and the
      in vivo phenotypes were explored. RESULTS: Widespread changes of DNA methylation
      were observed during development of highly aggressive cell lines. Up to 2.5% of
      the CpG-rich region was differentially methylated as identified by reduced
      representation bisulfite sequencing compared with the less aggressive parental
      cell lines. DNA methyltransferase inhibition by azacytidine reversed the
      prometastatic phenotype; this was highly associated with the preferential loss of
      DNA methylation at sites that were hypermethylated during the in vivo selection.
      Of note, polycomb (PRC2) binding sites were particularly affected by DNA
      methylation changes after azacytidine exposure that persisted over time.
      CONCLUSIONS: We could show that metastatic capability of NSCLC is closely
      associated with DNA methylome alterations. Because inhibition of DNA
      methyltransferase reversed metastasis-prone phenotype, epigenetic modulation
      seems to be a potential therapeutic approach to prevent metastasis formation.

PMID- 24334762
TI  - T lymphocytes redirected against the chondroitin sulfate proteoglycan-4 control
      the growth of multiple solid tumors both in vitro and in vivo.
AB  - PURPOSE: Because of its high expression on various types of tumors and its
      restricted distribution in normal tissues, chondroitin sulfate proteoglycan-4
      (CSPG4) represents an attractive target for the antibody-based therapy of several
      solid tumors. We tested whether T cells transduced with a CSPG4-specific chimeric
      antigen receptor (CAR) inhibited the growth of CSPG4-expressing tumor cells both
      in vitro and in vivo. EXPERIMENTAL DESIGN: We first independently validated by
      immunohistochemistry (IHC) the expression of CSPG4 in an extensive panel of tumor
      arrays and normal tissues as well as queried public gene expression profiling
      datasets of human tumors. We constructed a second-generation CSPG4-specific CAR
      also encoding the CD28 costimulatory endodomain (CAR.CSPG4). We then evaluated
      human T lymphocytes expressing this CAR for their ex vivo and in vivo antitumor
      activity against a broad panel of solid tumors. RESULTS: IHC showed that CSPG4 is
      highly expressed in melanoma, breast cancer, head and neck squamous cell
      carcinoma (HNSCC), and mesothelioma. In addition, in silico analysis of
      microarray expression data identified other important potential tumors expressing
      this target, including glioblastoma, clear cell renal carcinoma, and sarcomas. T
      lymphocytes genetically modified with a CSPG4-CAR controlled tumor growth in
      vitro and in vivo in NSG mice engrafted with human melanoma, HNSCC, and breast
      carcinoma cell lines. CONCLUSIONS: CAR.CSPG4-redirected T cells should provide an
      effective treatment modality for a variety of solid tumors.

PMID- 24334764
TI  - Cohen syndrome is associated with major glycosylation defects.
AB  - Cohen syndrome (CS) is a rare autosomal recessive disorder with multisytemic
      clinical features due to mutations in the VPS13B gene, which has recently been
      described encoding a mandatory membrane protein involved in Golgi integrity. As
      the Golgi complex is the place where glycosylation of newly synthesized proteins
      occurs, we hypothesized that VPS13B deficiency, responsible of Golgi apparatus
      disturbance, could lead to glycosylation defects and/or mysfunction of this
      organelle, and thus be a cause of the main clinical manifestations of CS. The
      glycosylation status of CS serum proteins showed a very unusual pattern of
      glycosylation characterized by a significant accumulation of agalactosylated
      fucosylated structures as well as asialylated fucosylated structures
      demonstrating a major defect of glycan maturation in CS. However, CS transferrin
      and alpha1-AT profiles, two liver-derived proteins, were normal. We also showed
      that intercellular cell adhesion molecule 1 and LAMP-2, two highly glycosylated
      cellular proteins, presented an altered migration profile on SDS-PAGE in
      peripheral blood mononuclear cells from CS patients. RNA interference against
      VPS13B confirmed these glycosylation defects. Experiments with Brefeldin A
      demonstrated that intracellular retrograde cell trafficking was normal in CS
      fibroblasts. Furthermore, early endosomes were almost absent in these cells and
      lysosomes were abnormally enlarged, suggesting a crucial role of VPS13B in
      endosomal-lysosomal trafficking. Our work provides evidence that CS is associated
      to a tissue-specific major defect of glycosylation and endosomal-lysosomal
      trafficking defect, suggesting that this could be a new key element to decipher
      the mechanisms of CS physiopathology. 

PMID- 24334766
TI  - Dysregulation of T cell receptor N-glycosylation: a molecular mechanism involved
      in ulcerative colitis.
AB  - The incidence of inflammatory bowel disease is increasing worldwide and the
      underlying molecular mechanisms are far from being fully elucidated. Herein, we
      evaluated the role of N-glycosylation dysregulation in T cells as a key mechanism
      in the ulcerative colitis (UC) pathogenesis. The evaluation of the branched N
      glycosylation levels and profile of intestinal T cell receptor (TCR) were
      assessed in colonic biopsies from UC patients and healthy controls. Expression
      alterations of the glycosyltransferase gene MGAT5 were also evaluated. We
      demonstrated that UC patients exhibit a dysregulation of TCR branched N
      glycosylation on lamina propria T lymphocytes. Patients with severe UC showed the
      most pronounced defect on N-glycan branching in T cells. Moreover, UC patients
      showed a significant reduction of MGAT5 gene transcription in T lymphocytes. In
      this study, we disclose for the first time that a deficiency in branched N
      glycosylation on TCR due to a reduced MGAT5 gene expression is a new molecular
      mechanism underlying UC pathogenesis, being a potential novel biomarker with
      promising clinical and therapeutic applications. 

PMID- 24334765
TI  - The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and
      modulates endolysosomal function.
AB  - TMEM127 is an endosome-associated tumor suppressor gene in pheochromocytomas,
      neuroendocrine tumors that can co-occur with renal cell carcinomas (RCCs).
      TMEM127 loss leads to increased mTOR signaling. However, the spectrum of tumors
      with TMEM127 mutation and how TMEM127 and mTOR interact in tumorigenesis remains
      unknown. Here, we report that germline TMEM127 mutations occur in RCCs and that
      some mutant proteins, unlike wild-type (WT) TMEM127, fail to cooperate with
      activated early endosomal GTPase, Rab5, to inhibit mTOR signaling. Tmem127-null
      mouse embryonic fibroblasts (MEFs) are deficient in generating early-to-late
      hybrid endosomes upon constitutive Rab5 activation, a defect rescued by WT, but
      not mutant, TMEM127. This endosomal dysfunction results in diminished mTOR
      colocalization with Rab5-positive vesicles. Conversely, active, lysosomal-bound
      mTOR is increased in Tmem127-null MEFs, which also display enhanced lysosomal
      biogenesis. Our data map the tumor-suppressive properties of TMEM127 to
      modulation of mTOR function in the endolysosome, a feature that may contribute to
      both pheochromocytoma and RCC pathogenesis. 

PMID- 24334767
TI  - Germline mutations in FH confer predisposition to malignant pheochromocytomas and
      paragangliomas.
AB  - Malignant pheochromocytoma (PCC) and paraganglioma (PGL) are mostly caused by
      germline mutations of SDHB, encoding a subunit of succinate dehydrogenase. Using
      whole-exome sequencing, we recently identified a mutation in the FH gene encoding
      fumarate hydratase, in a PCC with an 'SDH-like' molecular phenotype. Here, we
      investigated the role of FH in PCC/PGL predisposition, by screening for germline
      FH mutations in a large international cohort of patients. We screened 598
      patients with PCC/PGL without mutations in known PCC/PGL susceptibility genes. We
      searched for FH germline mutations and large deletions, by direct sequencing and
      multiplex ligation-dependent probe amplification methods. Global alterations in
      DNA methylation and protein succination were assessed by immunohistochemical
      staining for 5-hydroxymethylcytosine (5-hmC) and S-(2-succinyl) cysteine (2SC),
      respectively. We identified five pathogenic germline FH mutations (four missense
      and one splice mutation) in five patients. Somatic inactivation of the second
      allele, resulting in a loss of fumarate hydratase activity, was demonstrated in
      tumors with FH mutations. Low tumor levels of 5-hmC, resembling those in SDHB
      deficient tumors, and positive 2SC staining were detected in tumors with FH
      mutations. Clinically, metastatic phenotype (P = 0.007) and multiple tumors (P =
      0.02) were significantly more frequent in patients with FH mutations than those
      without such mutations. This study reveals a new role for FH in susceptibility to
      malignant and/or multiple PCC/PGL. Remarkably, FH-deficient PCC/PGLs display the
      same pattern of epigenetic deregulation as SDHB-mutated malignant PCC/PGL.
      Therefore, we propose that mutation screening for FH should be included in
      PCC/PGL genetic testing, at least for tumors with malignant behavior. 

PMID- 24334768
TI  - Defining the action spectrum of potential PGC-1alpha activators on a
      mitochondrial and cellular level in vivo.
AB  - Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC
      1alpha activation in cellular and murine model of disorders linked to
      mitochondrial dysfunction. While in some cases, this effect seems to be clearly
      associated with boosting of mitochondrial function, additional alterations as
      well as tissue- and cell-type-specific effects might play an important role. We
      initiated a comprehensive analysis of the effects of potential PGC-1alpha
      activating drugs and pharmaceutically targeted the PPAR (bezafibrate,
      rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa
      cells, neuronal cells and PGC-1alpha-deficient MEFs to get insight into cell type
      specificity and PGC-1alpha dependence of their working action. We used
      bezafibrate as a model drug to assess the effect on a tissue-specific level in a
      murine model. Not all analyzed drugs activate the PGC pathway or alter
      mitochondrial protein levels. However, they all affect supramolecular assembly of
      OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and
      cell-type-specific influence on several cellular stress pathways as well as on
      post-translational modifications could be demonstrated, which might be relevant
      to fully understand the action of the analyzed drugs in the disease state.
      Importantly, the effect on the activation of mitochondrial biogenesis and stress
      response program upon drug treatment is PGC-1alpha dependent in MEFs
      demonstrating not only the pleiotropic effects of this molecule but points also
      to the working mechanism of the analyzed drugs. The definition of the action
      spectrum of the different drugs forms the basis for a defect-specific
      compensation strategy and a future personalized therapeutic approach. 

PMID- 24334769
TI  - Mutations in the collagen XII gene define a new form of extracellular matrix
      related myopathy.
AB  - Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease
      characterized by contractures and proximal weakness, which can be caused by
      mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However,
      there may be additional causal genes to identify as in ~50% of BM cases no
      mutations in the COL6 genes are identified. In a cohort of -24 patients with a BM
      like phenotype, we first sequenced 12 candidate genes based on their function,
      including genes for known binding partners of collagen VI, and those enzymes
      involved in its correct post-translational modification, assembly and secretion.
      Proceeding to whole-exome sequencing (WES), we identified mutations in the
      COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with
      interrupted triple helices) in five individuals from two families. Both families
      showed dominant inheritance with a clinical phenotype resembling classical BM.
      Family 1 had a single-base substitution that led to the replacement of one
      glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating
      pattern, and Family 2 had a missense mutation, which created a mutant protein
      with an unpaired cysteine residue. Abnormality at the protein level was confirmed
      in both families by the intracellular retention of collagen XII in patient dermal
      fibroblasts. The mutation in Family 2 leads to the up-regulation of genes
      associated with the unfolded protein response (UPR) pathway and swollen,
      dysmorphic rough-ER. We conclude that the spectrum of causative genes in
      extracellular matrix (ECM)-related myopathies be extended to include COL12A1. 

PMID- 24334771
TI  - [Education effect of the simple suspension method training for fifth-year medical
      students].
AB  - The clinical training curriculum for fifth-year students of a school of medicine
      (Department of Medicine) includes training in clinical pharmacy, which is
      conducted by the Department of Pharmacy. Following training involving the simple
      suspension method, a survey was conducted to examine its effects to improve
      medical students' knowledge on the proper use of drugs. Forty-eight 5th-year
      students of Ehime University School of Medicine, Department of Medicine,
      underwent training that employed the simple suspension method, and examinations
      were conducted prior to and following it to assess its effects. Following the
      training, the questionnaire results were analyzed using Quantification Theory
      Class II to examine whether knowledge acquired from it had motivated the students
      to use the simple suspension method. A correspondence structural analysis was
      also conducted to identify improvements in the training. The correct answer rate
      increased from 55.2+/-2.4% before to 83.8+/-1.7% after training, which supports
      its learning effects. The presence or absence of changes in disposition and the
      efficacy of the method for patients with dysphagia strongly motivated the medical
      students to use the method. As a future improvement, it is necessary to describe
      differences between the crushing and simple suspension methods during training.
      The results of a survey on training involving medical students conducted based on
      the simple suspension method suggested its learning effects and knowledge that
      motivated them to use the method.

PMID- 24334770
TI  - Zn2+ dyshomeostasis caused by loss of ATP13A2/PARK9 leads to lysosomal
      dysfunction and alpha-synuclein accumulation.
AB  - Mutations in ATP13A2 (PARK9) cause Kufor-Rakeb syndrome (KRS) characterized by
      juvenile-onset parkinsonism, pyramidal signs and dementia. PARK9 belongs to type
      5 P-type ATPase with its putative function as a cation transporter. Loss of PARK9
      leads to lysosomal dysfunction and subsequent alpha-synuclein (alpha-Syn)
      accumulation. However, the mechanistic link between PARK9 and lysosomal
      dysfunction remains unclear. Here, we found that patient fibroblasts expressing
      mutant PARK9 or primary neurons with silenced PARK9 exhibited increased
      sensitivity to extracellular zinc (Zn(2+)). This effect was rescued with the
      Zn(2+) chelators clioquinol or TPEN. PARK9-deficient cells showed decreased
      lysosomal sequestration of Zn(2+) and increased expression of zinc transporters.
      Importantly, increased concentrations of Zn(2+) (Zn(2+) stress) resulted in
      lysosomal dysfunction that was partially restored by expression of wild-type
      PARK9. Zn(2+) stress also caused increased expression of alpha-Syn and
      consequently decreased activity of the lysosomal enzyme glucocerebrosidase.
      Together, these data suggest that PARK9 loss of function leads to dyshomeostasis
      of intracellular Zn(2+) that in turn contributes to lysosomal dysfunction and
      accumulation of alpha-Syn. It will be of interest to examine whether therapeutic
      lowering of zinc may prove beneficial for patients with KRS. 

PMID- 24334772
TI  - Austria: health system review.
AB  - This analysis of the Austrian health system reviews recent developments in
      organization and governance, health financing, health-care provision, health
      reforms and health-system performance. The Austrian health system provides
      universal coverage for a wide range of benefits and high-quality care. Free
      choice of providers and unrestricted access to all care levels (general
      practitioners, specialist physicians and hospitals) are characteristic features
      of the system. Unsurprisingly, population satisfaction is well above EU average.
      Income-related inequality in health has increased since 2005, although it is
      still relatively low compared to other countries. The health-care system has been
      shaped by both the federal structure of the state and a tradition of delegating
      responsibilities to self-governing stakeholders. On the one hand, this enables
      decentralized planning and governance, adjusted to local norms and preferences.
      On the other hand, it also leads to fragmentation of responsibilities and
      frequently results in inadequate coordination. For this reason, efforts have been
      made for several years to achieve more joint planning, governance and financing
      of the health-care system at the federal and regional level. As in any health
      system, a number of challenges remain. The costs of the health-care system are
      well above the EU15 average, both in absolute terms and as a percentage of GDP.
      There are important structural imbalances in healthcare provision, with an
      oversized hospital sector and insufficient resources available for ambulatory
      care and preventive medicine. This is coupled with stark regional differences in
      utilization, both in curative services (hospital beds and specialist physicians)
      and preventative services such as preventive health check-ups, outpatient
      rehabilitation, psychosocial and psychotherapeutic care and nursing. There are
      clear social inequalities in the use of medical services, such as preventive
      health check-ups, immunization or dentistry. One of the key weaknesses of the
      health-care system is in the prevention of illness. Spending on preventive
      medicine, at 2% of total health spending, is significantly lower than the EU15
      and OECD average (both 3%), and also shows a below-average rate of growth. It
      remains to be seen whether the focus on health promotion and prevention of the
      'framework health goals' approved in 2012 will be translated into concrete
      measures, whether clear responsibilities for implementation can be assigned, and
      whether sufficient funding will be made available. This would be likely to
      improve the health of the Austrian population and would help to reduce costs
      associated with preventable diseases. 

PMID- 24334774
TI  - Humans as donors and producers of biological material: some ethical
      considerations on a thin red line.

PMID- 24334773
TI  - Effective dose in SMAW and FCAW welding processes using rutile consumables.
AB  - The shielded metal arc welding (SMAW) and flux cored arc welding (FCAW) processes
      use covered electrodes and flux cored wire as consumables. Among these
      consumables, ones containing rutile are the most widely used, and since they have
      a considerable natural radioactive content, they can be considered as NORM
      (naturally occurring radioactive material). To calculate the effective dose on
      workers during their use in a conservative situation, samples of slag and
      aerosols and particles emitted or deposited during welding were taken and
      measured by gamma, alpha and beta spectrometry. An analytical method was also
      developed for estimating the activity concentration of radionuclides in the
      inhaled air. (222)Rn activity concentration was also assessed. With all these
      data, internal and external doses were calculated. The results show that external
      doses are negligible in comparison with internal ones, which do not exceed 1 mSv
      yr(-1), either in this conservative situation or in any other more favourable
      one. Radionuclides after Rn in the radioactive natural series are emitted at the
      same activity concentration to the atmosphere, this being around 17 times higher
      than that corresponding to radionuclides before Rn. Taking into account these
      conclusions and the analytical method developed, it can be concluded that one way
      to assess the activity concentration of natural radionuclides in inhaled air and
      hence effective doses could be the early gamma-ray spectrometry of aerosols and
      particles sampled during the welding process.

PMID- 24334775
TI  - Detention and incompatibility of HIV patients in Italy. .
AB  - In Italy, Law 231/99 and subsequent amendments standardize the conditions
      allowing or not a HIV positive inmate to remain in jail. Currently such clinical
      conditions are not automatically associated with the decline of preventive
      detention and the Court evaluates the incompatibility with detention on the basis
      of two additional and independent criteria. We have been observing the tendency
      by jailed HIV-positive patients to manipulate the disease state believing that
      the rules of incompatibility with the prison system are always applied. The
      management of HIV positive patients in jail involves significant sanitary and
      relational efforts, particularly for those suffering AIDS and/or with severe
      immunodeficiency. 

PMID- 24334776
TI  - Post-operative hospitalization in retinal detachment correlation to recurrences.
AB  - PURPOSE: To evaluate relationships between the incidence of re-detachment and
      postoperative days of hospitalization in patients with diagnosis of retinal
      detachment (RD) who underwent surgery either through ab-externo approach (scleral
      buckling and encircling) or ab-interno approach (vitrectomy and oil-gas
      tamponade). METHODS: This retrospective study included 268 patients (268 eyes)
      with diagnosis of primary RD: 127 males (47%) and 141 (53%) females, mean age of
      64.1 +/- 17.3 years. 46 patients (17%) underwent a surgical ab-externo approach
      (group A), while 222 patients (83%) underwent an ab-interno surgical approach.
      Each RD was graded according to the "Retinal detachment grading system of Royal
      College of Ophthalmologists" and treated within 5 days after diagnosis. The
      redetachment (RT) related to a surgical failure was considered within 30 days
      after first operation. RESULTS: In the group 1 without night hospitalization (day
      surgery) global RT rate was 3.5% (4.17% for ab-interno technique and 0% for ab
      externo techniques). In the group 2 with one day of hospitalization global RT
      rate was 1.33% (1.49% for ab-interno technique and 0% for ab-externo techniques).
      In the group 3 with 2 days of hospitalization global RT rate was 3.80% (4.62% for
      ab-interno techniques and 0% for ab-externo techniques). In the group 4 with 3 or
      more days of hospitalization global RT rate was 12.28% (14.29% for ab-interno
      techniques for 6.67% ab-externo techniques). The incidence of RT in group 1, day
      surgery, is comparable to the other groups and it is less compared to group 4 (3
      or more days of hospitalization). CONCLUSIONS: The incidence of retinal
      redetachment (RRD) is not increased in day surgery mode. These data support
      outpatient management of RD patients to reduce medical cost and problems related
      to the hospitalization. Further studies are needed for patients' security.

PMID- 24334777
TI  - Dietary habits and growth: an urban/rural comparison in the Andean region of
      Apurimac, Peru.
AB  - INTRODUCTION: The efficacy of interventions against children malnutrition
      crucially depends on a myriad of factors other than the simple food intake, that
      must be carefully studied in order to plan a balanced policy. The relation
      between dietary patterns and growth is at the very heart of the problem,
      especially in consideration of the fact that dietary pattern involves dimension
      other than pure caloric intake in its definition. In this work we investigated
      the relations between dietary pattern and growth comparing children from a rural
      and a urban area in Andean Peru, in terms of food habits and anthropometric
      variables to develop a model usable in context interventions against
      malnutrition. MATERIAL AND METHODS: A sample of 159 children (80 from urban, 79
      from rural area), aged from 4 to 120 months (72.7 +/- 37.5 SD) was collected. The
      data were investigated by a multidimensional (principal component analysis
      followed by inferential approach) analysis to correlate the different hidden
      dimensions of both anthropometric and dietary observables. The correlation
      between these dimensions (in the form of principal components) were computed and
      contrasted with the effects of age and urban/rural environments. RESULTS: Caloric
      intake and growth were not linearly correlated in our data set. Moreover urban
      and rural environment were demonstrated to show very different patterns of both
      dietary and anthropometric variables pointing to the marked effect of dietary
      habits and demographic composition of the analyzed populations. The relation
      between malnutrition and overweight was at the same time demonstrated to follow a
      strict area-dependent distribution. DISCUSSION AND CONCLUSION: We gave a proof-of
      concept of the non-linear character of the relation between malnutrition (in
      terms of caloric intake) and growth, pointing to the need to calibrate
      interventions on food pattern and not only quantity to contrast malnutrition
      effects on growth. The education toward a balanced diet must go hand-in-hand with
      the intervention on caloric intake in order to prevent effects on health.

PMID- 24334778
TI  - Ethics in public health surveillance.
AB  - Public health programmes pose some very important ethical problems. One of the
      most pressing is the possible conflict between individual interests (and rights)
      and collective interests, which becomes particularly important in the public
      health surveillance setting. The present article first looks at the definitions
      of "public health surveillance" in a historical context and then identifies the
      key ethical problems that are raised. These reveal the differences - and
      sometimes deviations - between the bioethical issues typically encountered in a
      clinical setting and those that prevail in a public health context. Human rights
      are suggested as a possible common ground between the two. The article then draws
      on the specialised literature to indicate tools and checklists to help evaluate
      the ethical acceptability of public health surveillance programmes. It concludes
      with a description of the key criteria underlying these tools and checklists. 

PMID- 24334779
TI  - Cohort study of residents of a district with soil and groundwater industrial
      waste contamination.
AB  - INTRODUCTION: A neighbourhood of the city of Ferrara (Italy) was built over an
      area polluted with chlorinated organic compounds. A residential cohort study was
      performed to assess the health profile of the population living in the polluted
      area. METHODS: The residential history of 3475 subjects who had lived in the East
      quadrant neighbourhood in the period 1994-2010 was constructed. Mortality for the
      period 1994- 2010 and cancer incidence for the years 1994-2007 were studied.
      Standardised mortality ratios (SMR) for 2632 subjects and standardised incidence
      ratios (SIR) for 2578 subjects who had lived for at least 5 years in the area
      under study were calculated. Indicators were calculated for males and females
      combined, using the population of Ferrara as reference population. RESULTS: The
      health profile of the population of the East quadrant neighbourhood, defined
      using mortality indicators for major groups of causes, is essentially similar to
      that of the city of Ferrara. Increased mortality rates for lung cancer (SMR 131,
      90% CI 94-178) and incidence rates for some cancer sites, including liver (SIR
      135, 90% CI 67-243) were observed, albeit on the basis of few cases and with wide
      confidence intervals. DISCUSSION: The likelihood of observing significant
      increases in risk is reduced by the sizes of the cohorts and the short follow-up
      period, but some findings nonetheless suggest that, as a precautionary measure,
      the cohort study should be continued in parallel with measures for the
      reclamation of the site and that this study should take the form of
      epidemiological surveillance.

PMID- 24334780
TI  - Can reinforcement-based interventions to reduce drug use successfully be adapted
      to routine opioid maintenance treatment?
AB  - INTRODUCTION: Comorbid substance related disorders are a major health problem for
      patients in opioid maintenance treatment (OMT). It was investigated whether a
      reinforcement scheme adapted to the regulatory and financial restrictions of
      routine treatment reduces concomitant drug use. METHODS: OMT patients from 7
      clinics who were using cocaine, benzodiazepines, heroin or amphetamines were
      randomly allocated to either treatment as usual (n = 64) or treatment with an
      additional escalating reinforcement scheme (n = 72) in which a patient's number
      of weekly take-home dosages was increased after 1, 4, 8 and 12 consecutive weeks
      with drug-free urine specimens. Trial duration was 26 weeks. RESULTS: Completion
      rates were 64% for controls and 62.5% in the experimental group. Mean number of
      drug-free weeks was 11.3 (SD 8.5) for the control group and 9.8 (8.9) for the
      experimental group (p = 0.30). CONCLUSION: The intervention was not effective
      compared to routine treatment. Additional features might be necessary to achieve
      an effect, e.g. a higher frequency of urine sampling or use of other reinforcers.
      It has to be further investigated how interventions which have been proven
      effective in experimental studies can successfully be adapted to routine care
      conditions.

PMID- 24334781
TI  - The relationship between personality traits and anxiety/depression levels in
      different drug abusers' groups.
AB  - Aim. Since psychosocial characteristics of drug abuse involve mainly specific
      personality and emotional changes, it is very important to investigate
      characteristics of addictive personality in relationship with emotional state of
      the individual. Considering that, the objective of this study was to analyse the
      relationship between personality structure and emotional state of two different
      groups: heroin addicts and recreate drug abusers. Methods. The total of 288 (219
      males and 69 females; 191 heroin addicts and 97 recreate drug users) clients of
      Centre for the prevention and treatment of drug abuse in Rijeka completed
      Eysenck's Personality Questionnaire (EPQ R/A), Beck's Anxiety Inventory (BAI) and
      Beck's Depression Inventory (BDI). Their average age was 22. Results. In the
      group of heroin addicts, higher levels of anxiety and depression were
      significantly correlated with higher levels of psychoticism, neuroticism,
      criminality and addiction. In the group of recreate drug users, higher
      extraversion and social conformity were determined. Furthermore, in the first
      group was found even higher depression. However when the anxiety level was
      compared between these two groups, there was no significant difference.
      Conclusion. Overall, the findings implied that the used measurement instruments
      could serve as the useful diagnostic tools that could ensure advantageous
      treatment directions. 

PMID- 24334782
TI  - Characteristics of neonatal GBS disease during a multicentre study (2007-2010)
      and in the year 2012.
AB  - INTRODUCTION: The characteristics of Group B Streptococcal (GBS) early onset
      (EOD) and late onset (LOD) neonatal infections in Italy were analyzed. Two
      periods were considered, a first 3-years period (2007-2010), when notification of
      GBS infections was enforced under the auspices of the Italian Ministry of Health,
      and a second 1 year period (2012) when reporting on neonatal GBS disease
      continued on voluntary basis. METHODS: A standardized form was used to collect
      data on cases of neonatal GBS disease. They included both maternal and neonatal
      data. RESULTS AND DISCUSSION: The two surveys underlined that preterm deliveries,
      precipitous labor and negatively GBS screened mothers are common causes of EOD
      occurrence, possibly explained by inadequate, or lack of, intrapartum antibiotic
      prophylaxis. Nevertheless, measures for reducing prevention failures and EOD
      incidence by an higher adherence to prevention strategies, as the Centre for
      Disease Control recommendations, are still possible and should be encouraged.

PMID- 24334783
TI  - Epidemiology of home injuries: a large observational study among adult mothers in
      Italy.
AB  - AIMS: The aims of the study were to describe the epidemiology of home injuries
      (HI) among Italian students' mothers and to identify the possible predictors of
      having HI. METHODS: An anonymous questionnaire was used in several Italian
      schools. In order to identify predictors of having HI, a multivariate analysis
      was performed. RESULTS: In our sample (3,610 women), the prevalence of HI was
      18%; 6.2% of the interviewed had a severe HI. The multivariate analyses showed
      that increasing age, to spend more than 13 hours a day at home and to be
      housewife are risk factors for having HI. CONCLUSIONS: This study reports a high
      prevalence of HI, highlighting an urgent need for undertaking interventions to
      develop an adequate culture of safety and prevention.

PMID- 24334784
TI  - NGF and BDNF long-term variations in the thyroid, testis and adrenal glands of a
      mouse model of fetal alcohol spectrum disorders.
AB  - OBJECTIVES: Fetal Alcohol Spectrum Disorders (FASD) due to prenatal ethanol
      consumption may induce long-lasting changes to the newborns affecting also the
      endocrine system and the nerve growth factor (NGF) and brain derived neurotrophic
      factor (BDNF) signaling. Thus the aim of this study was to investigate in the
      thyroid, testis and adrenal glands of a FASD mouse model the long-lasting effects
      of ethanol exposure during pregnancy and lactation on NGF and BDNF and their main
      receptors, TrkA and TrkB, including their phosphorylated patterns. METHODS: We
      used aged male CD-1 mice early exposed to ethanol solution or red wine at same
      ethanol concentration (11% vol). RESULTS: We found elevations in NGF and BDNF in
      the thyroid of aged mice exposed to ethanol solution only but not in the red wine
      group. In the testis NGF resulted to be increased only in the ethanol solution
      group. In the adrenal glands data showed an elevation in NGF in both the ethanol
      solution group and red wine. No changes in TrkA, TrkB, phospho-TrkA and phospho
      TrkB were revealed in all tissues examined. CONCLUSIONS: Early administration of
      ethanol may induce long-lasting changes in the mouse thyroid, testis and adrenal
      glands at NGF and BDNF levels.

PMID- 24334785
TI  - Lessons learnt from a birthday party: a Bacillus cereus outbreak, Bari, Italy,
      January 2012.
AB  - INTRODUCTION: Bacillus cereus, a ubiquitous bacterium, can be isolated in various
      starchy food items, causing both emetic and diarrhoeal disease. The real burden
      of B. cereus outbreaks is actually poorly known in Italy. We report a B. cereus
      foodborne outbreak that occurred in a pub in Bari (Italy) on January 22nd 2012
      during a birthday party, promptly reported by the pub owner. MATERIALS AND
      METHODS: Between January 22nd and 24th 2012, we performed a retrospective cohort
      study among the guests of the party to identify risk factors associated with
      illness. Leftovers of different meals were available for microbiological
      analysis. Faecal specimens were collected from cases. RESULTS: A total of 12
      cases among the 13 customers (attack rate: 92%) were reported. All cases had
      consumed basmati rice and sweet and sour vegetables (aetiological fraction:
      100%). B. cereus was isolated from both basmati rice served during the party and
      faecal specimens. DISCUSSION: The close collaboration between the pub owner and
      the public health officers and the possibility to test food leftovers and stool
      samples contributed to prevent further cases.

PMID- 24334786
TI  - Referral patterns in elderly emergency department visits.
AB  - OBJECTIVE: To assess elderly individuals' demand for emergency department (ED)
      care, in terms of the characteristics, processes, outcomes, costs by referral
      pattern. DATA SOURCE: All ED visits involving patients aged 65 and older,
      extracted from the 2010 dataset of an Local Health Agency, in North-Eastern Italy
      (no. = 18 648). STUDY DESIGN: Retrospective cohort study. PRINCIPAL FINDINGS:
      Patients were referred by primary care professionals (PCPs) in 43.1% of cases,
      1.4% came from nursing homes (NH), and 55.5% were self-referred (SR). The SR
      group had a higher adjusted odds ratio (aOR) for non-urgent conditions (1.98 CI
      1.85-2.12), but a lower aOR for conditions amenable to ambulatory care (0.53 CI
      0.48-0.59), and a lower consumption of resources. The SR group tend to occur more
      frequently out of hours, and to coincide with a shorter stay at the ED, lower
      observation unit activation rates, lower hospitalization rates and a lower
      consumption of services than other two groups. The average costs for all
      procedures were lower for the SR patients (mean = 106.04 ? +/- SD 84.90 ?) than
      for those referred by PCPs (mean = 138.14 ? +/- SD 101.17 ?) or NH (mean = 143.48
      ? +/- SD 95.28 ?). CONCLUSION: Elderly patients coming in ED have different
      characteristics, outcomes and recourses consume by referral pattern.

PMID- 24334787
TI  - Bupropion perceived as a stimulant by two patients with a previous history of
      cocaine misuse.
AB  - BACKGROUND AND OBJECTIVE: Despite animal studies having shown a generalisation of
      the bupropion cue to cocaine, this drug has been used in cocaine abuse with mixed
      results. We here aimed at describing two cases which contradict current
      knowledge. CASE REPORTS: We describe two cases of former cocaine abusers who
      reported a cocaine-like sensation upon taking bupropion. Bupropion improved
      patients' depression without any increase in cocaine craving. One of the patients
      increased without doctor consultation his dose on an as needed basis.
      CONCLUSIONS: The issue of bupropion cue generalisation to cocaine needs further
      elucidation. People with past cocaine addiction need to be informed on the
      potential of bupropion to elicit cocaine-like cues and be invited to adhere to
      medical prescription, because bupropion has been associated with fatalities in
      some cases.

PMID- 24334788
TI  - Promotion of mental health in children of parents with a mental disorder.
AB  - Mental disorders are associated with many difficulties in the activities of daily
      living, work, relationships and family, and they determine high social and
      economic costs that represent an important public health problem. The literature
      has shown that children of parents with mental disorders grow up in environments
      that are potentially harmful to their mental health and are at risk of neglect
      and maltreatment. Interventions to prevent mental disorders and psychological
      symptoms of children of parents with mental disorders are effective but
      supporting these families is a complex task which requires both cooperation
      between departments and an interdisciplinary knowledge. A greater knowledge of
      the responses provided to assist families with dependent children and a mentally
      ill parent, could stimulate reflections on critical issues and government actions
      aimed at promoting and protecting the mental health of children.

PMID- 24334789
TI  - Between altruism and commercialisation: some ethical aspects of blood donation.
AB  - Numerous documents (declarations, codes, recommendations, guidelines) issued by
      eminent institutions recommend that the donation of blood should be voluntary and
      unremunerated. This does not preclude the possibility: 1) that donors receive
      some form of reimbursement; 2) that subsequent procedures, which inevitably incur
      costs, may involve considerable financial activity; 3) that legislation in some
      nations may allow trade in certain types of human biological material; 4) that
      voluntarily donated human blood be used to derive products that are subsequently
      marketed. The present article highlights some of the contradictions generated by
      these considerations and affirms that they do not undermine the primary duty to
      uphold the voluntary nature of donation. 

PMID- 24334790
TI  - Quantifying sources of bias in National Healthcare Safety Network laboratory
      identified Clostridium difficile infection rates.
AB  - OBJECTIVE: To assess the effect of multiple sources of bias on state- and
      hospital-specific National Healthcare Safety Network (NHSN) laboratory-identified
      Clostridium difficile infection (CDI) rates. DESIGN: Sensitivity analysis.
      SETTING: A total of 124 New York hospitals in 2010. METHODS: New York NHSN CDI
      events from audited hospitals were matched to New York hospital discharge billing
      records to obtain additional information on patient age, length of stay, and
      previous hospital discharges. "Corrected" hospital-onset (HO) CDI rates were
      calculated after (1) correcting inaccurate case reporting found during audits,
      (2) incorporating knowledge of laboratory results from outside hospitals, (3)
      excluding days when patients were not at risk from the denominator of the rates,
      and (4) adjusting for patient age. Data sets were simulated with each of these
      sources of bias reintroduced individually and combined. The simulated rates were
      compared with the corrected rates. Performance (ie, better, worse, or average
      compared with the state average) was categorized, and misclassification compared
      with the corrected data set was measured. RESULTS: Counting days patients were
      not at risk in the denominator reduced the state HO rate by 45% and resulted in
      8% misclassification. Age adjustment and reporting errors also shifted rates (7%
      and 6% misclassification, respectively). CONCLUSIONS: Changing the NHSN protocol
      to require reporting of age-stratified patient-days and adjusting for patient
      days at risk would improve comparability of rates across hospitals. Further
      research is needed to validate the risk-adjustment model before these data should
      be used as hospital performance measures.

PMID- 24334791
TI  - The need for advancements in the field of risk adjustment for healthcare
      associated infections.

PMID- 24334792
TI  - Contamination of healthcare workers' hands with Clostridium difficile spores
      after caring for patients with C. difficile infection.
AB  - OBJECTIVE: We determined the percentage of healthcare workers' (HCWs') hands
      contaminated with Clostridium difficile spores after caring for patients with C.
      difficile infection (CDI) and risk factors associated with contamination. DESIGN:
      Prospective study. SETTING: A French university hospital. METHODS: We compared
      the hand contamination rate among HCWs caring for patients with CDI (exposed
      group; n = 66) with that among an unexposed group (n = 44). Spores of C.
      difficile were recovered from the hands of HCWs after rubbing their fingers and
      palms in alcohol shortly after patient care. Associations between hand
      contamination and HCW category, type (patient or environment), and risk level
      (high or low risk) of HCW contacts and their respective duration as well as use
      of gloves were analyzed by bivariate and multivariate analysis. RESULTS: C.
      difficile spores were detected on 24% of HCWs' hands in the exposed group and on
      0% in the unexposed group (P < .001). In the exposed group, logistic regression,
      which adjusted for high-risk contact (ie, exposure to fecal soiling), contact
      with the environment, and contact with or without use of gloves, revealed that
      high-risk contact (adjusted odds ratio [aOR] per 1 contact increment, 2.78; 95%
      confidence interval [CI], 1.42-5.45; P = .003) and at least 1 contact without use
      of gloves (aOR, 6.26; 95% CI, 1.27-30.78; P = .02) were independently associated
      with HCW hand contamination by C. difficile spores. CONCLUSIONS: Nearly one
      quarter of HCWs have hands contaminated with C. difficile spores after routine
      care of patients with CDI. Hand contamination is positively associated with
      exposure to fecal soiling and lack of glove use.

PMID- 24334793
TI  - Healthcare workers' hands and Clostridium difficile spores: making progress?

PMID- 24334794
TI  - A mathematical model to evaluate the routine use of fecal microbiota
      transplantation to prevent incident and recurrent Clostridium difficile
      infection.
AB  - OBJECTIVE: Fecal microbiota transplantation (FMT) has been suggested as a new
      treatment to manage Clostridium difficile infection (CDI). With use of a
      mathematical model of C. difficile within an intensive care unit (ICU), we
      examined the potential impact of routine FMT. DESIGN, SETTING, AND PATIENTS: A
      mathematical model of C. difficile transmission, supplemented with prospective
      cohort, surveillance, and billing data from hospitals in the southeastern United
      States. METHODS: Cohort, surveillance, and billing data as well as data from the
      literature were used to construct a compartmental model of CDI within an ICU.
      Patients were defined as being in 1 of 6 potential health states: uncolonized and
      at low risk; uncolonized and at high risk; colonized and at low risk; colonized
      and at high risk; having CDI; or treated with FMT. RESULTS: The use of FMT to
      treat patients after CDI was associated with a statistically significant
      reduction in recurrence but not with a reduction in incident cases. Treatment
      after administration of high-risk medications, such as antibiotics, did not
      result in a decrease in recurrence but did result in a statistically significant
      difference in incident cases across treatment groups, although whether this
      difference was clinically relevant was questionable. CONCLUSIONS: Our study is a
      novel mathematical model that examines the effect of FMT on the prevention of
      recurrent and incident CDI. The routine use of FMT represents a promising
      approach to reduce complex recurrent cases, but a reduction in CDI incidence will
      require the use of other methods to prevent transmission.

PMID- 24334795
TI  - Fecal microbiota therapy: ready for prime time?

PMID- 24334796
TI  - Mortality among patients with methicillin-resistant Staphylococcus aureus USA300
      versus non-USA300 invasive infections: a meta-analysis.
AB  - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) has been found to be epidemiologically and microbiologically distinct from
      healthcare-associated MRSA. Most CA-MRSA infections are not invasive; however,
      fatal outcomes have been reported among healthy people with CA-MRSA invasive
      infections. Epidemiological studies have attributed a major burden of CA-MRSA
      infections in the United States to the predominant clone USA300. We investigated
      the association between USA300 invasive infections and mortality by conducting a
      systematic review and meta-analysis of studies that reported mortality rates
      associated with USA300 strains. METHODS: We searched PubMed, bibliographies of
      other publications, and gray literature between January 2001 and December 2013.
      Observational studies of patients with an invasive MRSA infection were included.
      The exposure of interest was presence of USA300 invasive infection. Studies were
      included only if they provided MRSA PFGE types and if corresponding mortality
      data were the measured outcome. We pooled crude odds ratios (cORs) using a random
      effects model. Woolf test of homogeneity and Q and I(2) statistics were assessed.
      RESULTS: Of 574 articles identified by the search strategy, 8 met the inclusion
      criteria. Risk of mortality was significantly lower among patients with USA300
      MRSA infections (pooled cOR, 0.63 [95% confidence interval (CI)], 0.49-0.81).
      There was a moderate degree of heterogeneity among study results (P = .29; I(2) =
      18%). Results were observed to be heterogeneous due to study design, quality of
      studies, and definition of mortality. CONCLUSIONS: MRSA invasive infection with
      USA300 does not appear to be associated with higher mortality compared with
      infections due to non-USA300 strains. Nevertheless, larger well-designed studies
      are warranted to further evaluate this association.

PMID- 24334797
TI  - Prevalence, prediction, and clonality of methicillin-resistant Staphylococcus
      aureus carriage at admission to medical units in Hong Kong, China.
AB  - OBJECTIVE: To determine the prevalence, risk factors, and molecular epidemiology
      of methicillin-resistant Staphylococcus aureus (MRSA) colonization at the time of
      admission to acute medical units and to develop a cost-effective screening
      strategy. METHODS: Nasal and groin screening cultures were performed for patients
      at admission to 15 acute medical units in all 7 catchment regions in Hong Kong.
      All MRSA isolates were subjected to spa typing. RESULTS: The overall carriage
      rate of MRSA was 14.3% (95% confidence interval [CI], 13.5-15.1). MRSA history
      within the past 12 months (adjusted odds ratio [OR], 4.60 [95% CI, 3.28-6.44]),
      old age home residence (adjusted OR, 3.32 [95% CI, 2.78-3.98]), and bed-bound
      state (adjusted OR, 2.19 [95% CI, 1.75-2.74]) were risk factors selected as MRSA
      screening criteria that provided reasonable sensitivity (67.4%) and specificity
      (81.8%), with an affordable burden (25.2%). spa typing showed that 89.5%
      (848/948) of the isolates were clustered into the 4 spa clonal complexes (CCs):
      spa CC1081, spa CC032, spa CC002, and spa CC4677. Patients colonized with MRSA
      spa types t1081 (OR, 1.77 [95% CI, 1.49-2.09]) and t4677 (OR, 3.09 [95% CI, 1.54
      6.02]) were more likely to be old age home residents. CONCLUSIONS: MRSA carriage
      at admission to acute medical units was prevalent in Hong Kong. Our results
      suggest that targeted screening is a pragmatic approach to increase the detection
      of the MRSA reservoir. Molecular typing suggests that old age homes are
      epicenters in amplifying the MRSA burden in acute hospitals. Enhancement of
      infection control measures in old age homes is important for the control of MRSA
      in hospitals.

PMID- 24334798
TI  - A multicenter case-case control study for risk factors and outcomes of
      extensively drug-resistant Acinetobacter baumannii bacteremia.
AB  - OBJECTIVE: Extensively drug resistant (XDR) Acinetobacter baumannii infections
      are increasing. Knowledge of risk factors can help to prevent these infections.
      METHODS: We designed a 1?1?1 case-case-control study to identify risk factors for
      XDR A. baumannii bacteremia in Singapore and Thailand. Case group 1 was defined
      as having infection due to XDR A. baumannii, and case group 2 was defined as
      having infection due to non-XDR A. baumannii. The control group comprised
      patients with blood cultures obtained to determine possible infection. RESULTS:
      There were 93 patients in each group. Pitt bacteremia score (adjusted odds ratio
      [aOR], 2.570 [95% confidence interval (CI), 1.528-4.322]), central venous
      catheters (CVCs; aOR, 12.644 [95% CI, 2.143-74.620]), use of carbapenems (aOR,
      54.391 [95% CI, 3.869-764.674]), and piperacillin-tazobactam (aOR, 55.035 [95%
      CI, 4.803-630.613]) were independently associated with XDR A. baumannii
      bacteremia. In case group 2, Pitt bacteremia score (aOR, 1.667 [95% CI, 1.265
      2.196]) and third-generation cephalosporins (aOR, 2.965 [95% CI, 1.224-7.182])
      were independently associated with non-XDR A. baumannii bacteremia. Concurrent
      infections (aOR, 3.527 [95% CI, 1.479-8.411]), cancer (aOR, 3.172 [95% CI, 1.135
      8.865]), and respiratory source (aOR, 2.690 [95% CI, 1.160-6.239]) were
      associated with an increased risk of 30-day mortality. Survivors received more
      active empirical therapy (16.7% vs 9.6%; P = .157), had fewer cases of XDR
      bacteremia (45.8% vs 52.6%; P = .452), and received higher median definitive
      polymyxin B doses (840,000 units vs 700,000 units; P = .339) CONCLUSIONS: Use of
      CVC and broad spectrum antibiotics were unique risk factors of XDR A. baumannii
      bacteremia. Effective antimicrobial stewardship together with use of a CVC bundle
      may reduce the incidence of these infections. Risk factors of acquisition and
      mortality may help identify patients for early initiation of polymyxin B therapy.

PMID- 24334800
TI  - Risk factors for peripheral intravenous catheter failure: a multivariate analysis
      of data from a randomized controlled trial.
AB  - OBJECTIVE: To assess the relative importance of independent risk factors for
      peripheral intravenous catheter (PIVC) failure. METHODS: Secondary data analysis
      from a randomized controlled trial of PIVC dwell time. The Prentice, Williams,
      and Peterson statistical model was used to identify and compare risk factors for
      phlebitis, occlusion, and accidental removal. SETTING: Three acute care hospitals
      in Queensland, Australia. PARTICIPANTS: The trial included 3,283 adult medical
      and surgical patients (5,907 catheters) with a PIVC with greater than 4 days of
      expected use. RESULTS: Modifiable risk factors for occlusion included hand,
      antecubital fossa, or upper arm insertion compared with forearm (hazard ratio
      [HR], 1.47 [95% confidence interval (CI), 1.28-1.68], 1.27 [95% CI, 1.08-1.49],
      and 1.25 [95% CI, 1.04-1.50], respectively); and for phlebitis, larger diameter
      PIVC (HR, 1.48 [95% CI, 1.08-2.03]). PIVCs inserted by the operating and
      radiology suite staff had lower occlusion risk than ward insertions (HR, 0.80
      [95% CI, 0.67-0.94]). Modifiable risks for accidental removal included hand or
      antecubital fossa insertion compared with forearm (HR, 2.45 [95% CI, 1.93-3.10]
      and 1.65 [95% CI, 1.23-2.22], respectively), clinical staff insertion compared
      with intravenous service (HR, 1.69 [95% CI, 1.30-2.20]); and smaller PIVC
      diameter (HR, 1.29 [95% CI, 1.02-1.61]). Female sex was a nonmodifiable factor
      associated with an increased risk of both phlebitis (HR, 1.64 [95% CI, 1.28
      2.09]) and occlusion (HR, 1.44 [95% CI, 1.30-1.61]). CONCLUSIONS: PIVC survival
      is improved by preferential forearm insertion, selection of appropriate PIVC
      diameter, and insertion by intravenous teams and other specialists. TRIAL
      REGISTRATION: The original randomized controlled trial on which this secondary
      analysis is based is registered with the Australian New Zealand Clinical Trials
      Registry (http://www.anzctr.org.au; ACTRN12608000445370).

PMID- 24334799
TI  - Eliminating central line-associated bloodstream infections: a national patient
      safety imperative.
AB  - BACKGROUND: Several studies demonstrating that central line-associated
      bloodstream infections (CLABSIs) are preventable prompted a national initiative
      to reduce the incidence of these infections. METHODS: We conducted a
      collaborative cohort study to evaluate the impact of the national "On the CUSP:
      Stop BSI" program on CLABSI rates among participating adult intensive care units
      (ICUs). The program goal was to achieve a unit-level mean CLABSI rate of less
      than 1 case per 1,000 catheter-days using standardized definitions from the
      National Healthcare Safety Network. Multilevel Poisson regression modeling
      compared infection rates before, during, and up to 18 months after the
      intervention was implemented. RESULTS: A total of 1,071 ICUs from 44 states, the
      District of Columbia, and Puerto Rico, reporting 27,153 ICU-months and 4,454,324
      catheter-days of data, were included in the analysis. The overall mean CLABSI
      rate significantly decreased from 1.96 cases per 1,000 catheter-days at baseline
      to 1.15 at 16-18 months after implementation. CLABSI rates decreased during all
      observation periods compared with baseline, with adjusted incidence rate ratios
      steadily decreasing to 0.57 (95% confidence intervals, 0.50-0.65) at 16-18 months
      after implementation. CONCLUSION: Coincident with the implementation of the
      national "On the CUSP: Stop BSI" program was a significant and sustained decrease
      in CLABSIs among a large and diverse cohort of ICUs, demonstrating an overall 43%
      decrease and suggesting the majority of ICUs in the United States can achieve
      additional reductions in CLABSI rates.

PMID- 24334801
TI  - Effect of preoperative antibiotic prophylaxis on surgical site infections
      complicating cardiac surgery.
AB  - OBJECTIVE: To evaluate the effect of an optimized policy for antibiotic
      prophylaxis on surgical site infection (SSI) rates in cardiac surgery. DESIGN:
      Prospective cohort study. SETTING: Tertiary medical center in Israel. METHODS:
      SSIs were recorded during a 10-year study period and ascertained through routine
      surveillance using the National Healthcare Safety Network (NHSN) methodology.
      Multivariable analyses were conducted to determine which significant covariates,
      including the administration of preoperative prophylaxis, affected these
      outcomes. RESULTS: A total of 2,637 of 3,170 evaluated patients were included,
      and the overall SSI rate was 8.4%. A greater than 50% reduction in SSI rates was
      observed in the last 4 years of the study. Overall and site-specific infection
      rates were similar for patients receiving cefazolin or vancomycin. SSIs developed
      in 206 (8.1%) of the 2,536 patients who received preoperative prophylaxis (within
      2 hours of the first incision) compared with 14 (13.9%) of 101 patients who
      received antibiotic prophylaxis at a different time (P = .04; odds ratio [OR],
      1.8; 95% confidence interval [CI], 1.0-3.3). After accounting for covariates,
      preoperative hospital stay (5 days or more), an NHSN risk category (2 or 3), age
      (60 years or more), surgeon's role, and the period of measurement were
      significantly associated with SSIs. Emergency surgery, age, surgeon's role, and
      nonpreoperative prophylaxis were found to be independent predictors of
      superficial SSI. CONCLUSIONS: We observed a progressive and significant decrease
      in SSI rates after the implementation of an infection control program that
      included an optimized policy of preoperative prophylaxis in cardiac surgery.

PMID- 24334802
TI  - Breast tissue expander-related infections: perioperative antimicrobial regimens.
AB  - OBJECTIVE: The rate of postmastectomy tissue expander (TE) infection remains
      excessively high, ranging between 2% and 24%. We hypothesized that current
      perioperative antimicrobial regimens utilized for breast TE reconstruction may be
      outdated as a result of recent changes in microflora and susceptibility patterns.
      DESIGN AND METHODS: We reviewed the records of all patients who had a TE
      reconstructive procedure and developed a definite breast TE infection between
      2003 and 2010 at MD Anderson Cancer Center. Antimicrobials were stratified into 3
      groups: systemic perioperative, local irrigation, and oral immediate
      postoperative antimicrobials. These were considered discordant if they did not
      target the isolated organisms, while a breakthrough infection was defined as an
      infection that occurred despite concordant antimicrobial coverage. RESULTS:
      Overall, 75 patients with a definite TE infection were identified. The most
      common organisms identified were methicillin-resistant Staphylococcus epidermidis
      (29%), methicillin-resistant Staphylococcus aureus (15%), and gram-negative rods
      (26%). The use of systemic perioperative antimicrobials was deemed discordant in
      51% of the cases. Although 79% of the patients received broad-spectrum
      perioperative local antimicrobial irrigation, 63% developed a breakthrough
      infection. Even though 61% received oral postoperative prophylactic
      antimicrobials, 63% of the times they were deemed discordant. CONCLUSIONS:
      Contrary to the proven effectiveness of a single dose of perioperative
      antibiotics, the common use of local antimicrobial irrigation and prolonged
      postoperative oral antibiotics appears to be an inadequate component of our
      preventive armamentarium. Also, because methicillin-resistant staphylococcal and
      pseudomonal infections occurred approximately 60% of the time, at institutions
      that have observed an increase of these organisms, it may be prudent that
      perioperative antimicrobials target these microorganisms.

PMID- 24334803
TI  - Active surveillance for carbapenem-resistant Enterobacteriaceae using stool
      specimens submitted for testing for Clostridium difficile.
AB  - Active surveillance to identify asymptomatic carriers of carbapenem-resistant
      Enterobacteriaceae (CRE) is a recommended strategy for CRE control in healthcare
      facilities. Active surveillance using stool specimens tested for Clostridium
      difficile is a relatively low-cost strategy to detect CRE carriers. Further
      evaluation of this and other risk factor-based active surveillance strategies is
      warranted. 

PMID- 24334804
TI  - Tropical healthcare epidemiology: weather determinants of the etiology of
      bloodstream infections in a Brazilian hospital.
AB  - We studied the influence of weather on the etiology of healthcare-associated
      bloodstream infections in a hospital in Brazil during the years 2005-2010.
      Monthly average temperatures were positively associated with higher incidence of
      gram-negative bacilli as a whole, Acinetobacter baumannii, and Enterobacter
      species. The same groups presented seasonal behavior in stochastic models. 

PMID- 24334805
TI  - Outbreak of bloodstream infections associated with multiuse dialyzers containing
      O-rings.
AB  - This report details an outbreak investigation conducted by the Los Angeles County
      Department of Public Health of 3 cases of bacterial infection among patients
      receiving hemodialysis who were treated at the same dialysis center in 2011.
      Improper disinfection of reusable dialyzers was hypothesized as the source of
      transmission. 

PMID- 24334806
TI  - Compatibility of hydrogen peroxide vapor room decontamination with physiological
      monitors.

PMID- 24334807
TI  - Reply to Daniell.

PMID- 24334808
TI  - Increased Clostridium difficile recurrences following combined proton pump
      inhibitor-metronidazole therapy.

PMID- 24334809
TI  - Identification of Clostridium difficile ribotype 027 for the first time in
      Mainland China.

PMID- 24334810
TI  - Increase in chlorhexidine minimal inhibitory concentration of Acinetobacter
      baumannii clinical isolates after implementation of advanced source control.

PMID- 24334811
TI  - What is the source of bloodstream infection due to vancomycin-resistant
      enterococci in persons with mucosal barrier injury?

PMID- 24334812
TI  - Measuring quality metrics to identify and monitor antimicrobial stewardship
      program quality improvement efforts.

PMID- 24334813
TI  - Needlestick injuries among healthcare workers of a tertiary care hospital in
      South India.

PMID- 24334814
TI  - Distribution of glucagon-like peptide (GLP)-2-immunoreactive cells in the chicken
      small intestine: antigen retrieval immunohistochemistry.
AB  - An antigen retrieval method for immunohistochemical staining of glucagon-like
      peptide (GLP)-2-immunoreactive cells was investigated in the chicken small
      intestine. GLP-2-immunoreactive cells were observed as open-typed endocrine cells
      in the villous epithelium and crypts on both antigen retrieval agent-treated and
      untreated preparations. No obvious differences were detected in morphological
      features of GLP-2-immunoreactive cells between treated and untreated
      preparations. The frequencies of occurrence of GLP-2-immunoreactive cells,
      however, were significantly different in treated and untreated preparations: in
      the proximal and distal regions of jejunum and ileum obtained from untreated
      preparations, the frequencies of occurrence were 0.5 +/- 0.2, 0.7 +/- 0.1, 0.9 +/
      0.2 and 1.5 +/- 0.3, respectively (cell numbers per mucosal area: cells/mm(2),
      mean +/- SD), whereas those from treated sections were 14.7 +/- 2.3, 19.8 +/-
      2.3, 23.5 +/- 4.7 and 34.6 +/- 4.9 cells/mm(2), respectively. These data indicate
      that this antigen retrieval method is able to make immunoreactive GLP-2 available
      for detection and that GLP-2 may act as one of the common hormones secreted by L
      cells in the chicken small intestine. 

PMID- 24334815
TI  - Development of duplex PCR assay for detection and differentiation of typical and
      atypical Melissococcus plutonius strains.
AB  - Melissococcus plutonius is the causative agent of an important honeybee disease,
      European foulbrood (EFB). In addition to M. plutonius strains with typical
      characteristics (typical M. plutonius), we recently reported the presence of
      atypical M. plutonius, which are phenotypically and genetically distinguished
      from typical M. plutonius. Because typical and atypical M. plutonius may have
      different pathogenic mechanisms, differentiation of these two types is very
      important for diagnosis and more effective control of EFB. In this study,
      therefore, a duplex PCR assay was developed to detect and differentiate typical
      and atypical M. plutonius rapidly and easily. On the basis of the results of
      comparative genomic analyses, we selected Na(+)/H(+) antiporter gene and Fur
      family transcriptional regulator gene as targets for detection of typical and
      atypical strains, respectively, by PCR. Under optimized conditions, the duplex
      PCR system using the designed primers successfully detected and differentiated
      all typical and atypical M. plutonius strain/isolates tested, while no product
      was generated from any other bacterial strains/isolates used in this study,
      including those isolated from healthy honeybee larval guts. Detection limits of
      the PCR were 50 copies of chromosome/reaction for both types, and it could detect
      typical and atypical M. plutonius directly from diseased honeybee larvae.
      Moreover, the duplex PCR diagnosed mixed infections with both M. plutonius types
      more precisely than standard culture methods. These results indicate that the
      duplex PCR assay developed in this study is extremely useful for precise
      diagnosis and epidemiological study of EFB. 

PMID- 24334816
TI  - Clinical utility of computed tomographic lung volumes in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Published data concerning the utility of computed tomography (CT)
      based lung volumes are limited to correlation with lung function. OBJECTIVES: The
      aim of this study was to evaluate the clinical utility of the CT expiratory-to
      inspiratory lung volume ratio (CT Vratio) by assessing the relationship with
      clinically relevant outcomes. METHODS: A total of 75 stable chronic obstructive
      pulmonary disease (COPD) patients having pulmonary function testing and
      volumetric CT at full inspiration and expiration were retrospectively evaluated.
      Inspiratory and expiratory CT lung volumes were measured using in-house software.
      Correlation of the CT Vratio with patient-centered outcomes, including the
      modified Medical Research Council (MMRC) dyspnea score, the 6-min walk distance
      (6MWD), the St. George's Respiratory Questionnaire (SGRQ) score, and
      multidimensional COPD severity indices, such as the BMI, airflow obstruction,
      dyspnea, and exercise capacity index (BODE) and age, dyspnea, and airflow
      obstruction (ADO), were analyzed. RESULTS: The CT Vratio correlated significantly
      with BMI (r = -0.528, p < 0.001). The CT Vratio was also significantly associated
      with MMRC dyspnea (r = 0.387, p = 0.001), 6MWD (r = -0.459, p < 0.001), and SGRQ
      (r = 0.369, p = 0.001) scores. Finally, the CT Vratio had significant
      correlations with the BODE and ADO multidimensional COPD severity indices (r =
      0.605, p < 0.001; r = 0.411, p < 0.001). CONCLUSION: The CT Vratio had
      significant correlations with patient-centered outcomes and multidimensional COPD
      severity indices.

PMID- 24334817
TI  - High definition OCT image of sharp calcium spicule.

PMID- 24334818
TI  - Prognostic factors in supratentorial ependymomas.

PMID- 24334819
TI  - A rare case of peritoneal disseminated angiosarcoma 20 years after ovarian cancer
      diagnosis.
AB  - Angiosarcoma is a rare form of sarcoma which may be either a primary tumor or it
      may result from previous irradiation because of another tumor. In this paper, we
      present a case of a female patient diagnosed as having peritoneal disseminated
      angiosarcoma 20 years after ovarian cancer treatment (surgery, chemotherapy and
      radiotherapy). The case was very atypical because of an extremely rare peritoneal
      location and disseminated nature of the changes. Based on the initial
      histological picture, poorly differentiated cancer metastasis was diagnosed,
      suggesting a recurrence of the ovarian cancer that had been diagnosed earlier.
      The time elapsed from the ovarian cancer diagnosis, history of the previous
      irradiation and concentration of tumor markers were the only additional clinical
      data provided to the pathologists, which ultimately contributed to a correct
      diagnosis. The case we present herein shows and emphasizes the importance of
      proper communication between a clinician and a pathologist, which is a
      prerequisite for a correct diagnosis and, consequently, for proper treatment of
      patients. It also confirms the high specificity of the HE4 (human epididymis
      protein 4) marker in the monitoring of ovarian cancer, which was within normal
      limits in spite of peritoneal tumor dissemination.

PMID- 24334820
TI  - A unique case of late complication of rectum mesh erosion after laparoscopic
      sacrocolpopexy.
AB  - Sacrocolpopexy, a surgical technique with a low morbidity rate, is a valid
      procedure for repairing vaginal vault prolapse. To our knowledge, only 1 case of
      rectum erosion after open sacrocolpopexy has been reported in the literature, and
      there is no record of any such incident after laparoscopic sacrocolpopexy. We
      report the first case of mesh erosion involving the rectum instead of the vagina
      assessed 8 years after laparoscopic sacrocolpopexy.

PMID- 24334821
TI  - Three-dimensional personalized dosimetry for 188Re liver selective internal
      radiation therapy based on quantitative post-treatment SPECT studies.
AB  - We demonstrate that accurate patient-specific distributions of microspheres
      labeled with 188Re and resulting absorbed doses can be obtained from single
      photon emission computed tomography (SPECT) studies performed after 188Re
      selective internal radiation therapy when accurate correction methods are
      employed in image reconstruction. Our quantitative image reconstruction algorithm
      includes corrections for attenuation, resolution degradations and scatter as well
      as a window-based compensation for contamination. The procedure has been
      validated using four phantom experiments containing an 18 ml cylindrical source
      (82-93 MBq of 188Re activity) simulating a liver tumor. In addition, we applied
      our approach to post-therapy SPECT studies of ten patients with progressive
      primary or metastatic liver carcinomas. Our quantitative algorithm accurately
      (within 9%) recovered 188Re activity from four phantom experiments. In addition,
      for two patients that received three scans, deviations remained consistent
      between the measured and the reconstructed activities that were determined from
      studies with differing severity of the dead-time effect. The analysis of absorbed
      doses for patient studies allowed us to hypothesize that D90 (the minimum dose
      received by 90% of the tumor volume) may be a reliable metric relating therapy
      outcomes to the calculated doses. Among several considered metrics, only D90
      showed statistically significant correlation with the overall survival.

PMID- 24334822
TI  - What 'misguided campaign' against single embryo transfer?

PMID- 24334824
TI  - Performance of direct estradiol immunoassays with human male serum samples.
AB  - BACKGROUND: Steroid immunoassays originally required solvent extraction,
      chromatography, and structurally authentic tracers to avoid interference from
      steroid cross-reactivity and matrix effects. The demand for steroid assays has
      driven assay simplification, bypassing this triplet of validity criteria to allow
      use of unextracted serum, which has introduced bias and nonspecificity at low
      steroid concentrations. We aimed to evaluate the performance of commercial direct
      estradiol (E2) immunoassays relative to the reference method of LC-MS and
      compared serum E2 measurements from each assay with biomarkers of estrogen
      action. METHODS: We measured serum E2 in duplicate using 5 commercial direct
      immunoassays and LC-MS in a nested cohort of 101 healthy, asymptomatic men >40
      years old from the Healthy Man Study. For each immunoassay, we evaluated the
      detectability and distribution of serum E2 measurements, CV, and bias (relative
      to LC-MS) by Passing-Bablok regression and deviance plots. RESULTS: Three assays
      detected E2 in all samples, whereas E2 was detected in only 53% and 72% of
      samples by 2 other assays. All 5 assays had positive biases, ranging from 6% to
      74%, throughout their ranges. CVs were lower with 4 immunoassays than with LC-MS.
      LC-MS, but none of the direct immunoassays, correlated with serum testosterone
      and sex steroid-binding globulin. CONCLUSIONS: The positive bias of direct E2
      immunoassays throughout their working range reflects the nonspecific effects of
      steroid cross-reactivity and/or matrix interference arising from the violation of
      the triplet validity criteria for steroid immunoassay.

PMID- 24334823
TI  - The cGMP signaling pathway as a therapeutic target in heart failure with
      preserved ejection fraction.

PMID- 24334825
TI  - Everolimus-eluting stent for the treatment of bare metal in-stent restenosis:
      clinical and angiographic outcomes at nine-month follow-up of XERES (Xience
      Evaluation in bare metal stent REStenosis) trial.
AB  - AIMS: Restenosis is a frequent complication of coronary stent implantation,
      especially bare metal stent (BMS) implantation. The everolimus-eluting stent
      (EES) has previously been shown to be efficacious in the treatment of de novo
      lesions. We performed this study to evaluate clinical, angiographic and IVUS
      results after EES implantation for the treatment of BMS ISR. XERES was a
      prospective, multicentre, nationwide study, enrolling 97 consecutive patients
      with in-stent restenosis (ISR) after BMS implantation across 20 centres in
      France. Suitable lesions had a reference vessel diameter between 2.5 mm and 4 mm,
      a length <=22 mm and a diameter stenosis between 50 and 100%. The primary
      endpoint was angiographic in-stent late loss (LL) as determined by quantitative
      coronary angiography (QCA) at nine-month follow-up. QCA was required to be
      performed in each included patient and IVUS was performed in a subgroup of 27
      patients. At nine-month follow-up, the in-stent late loss was 0.35+/-0.63 mm. The
      rate of in-stent binary restenosis was 12.22%, including two complete occlusions.
      The average volume of neointimal hyperplasia was 15.6+/-9.9 mm3. The in-stent
      percent volume obstruction was 8.5+/-5.2%. The in-segment percent area and
      diameter obstruction were 32+/-17% and 27+/-11%, respectively. Two initial
      malappositions were persistent and two other patients had late acquired stent
      malapposition. The cumulative incidence of major adverse cardiac events (MACE)
      was 10.1%. EES for the treatment of bare metal in-stent restenosis seemed safe
      and efficacious.

PMID- 24334826
TI  - Maternal lipid change in relation to length of gestation: a prospective cohort
      study with preconception enrollment of women.
AB  - BACKGROUND/AIMS: We sought to investigate the association between preconception
      serum lipids and their daily rate of change in relation to length of gestation.
      METHODS: In a cohort of 70 women, 61 (87%) became pregnant, resulting in 48 (69%)
      live births. Serum lipid measurements (in milligrams per deciliter) included
      total cholesterol, free cholesterol, triglycerides and phospholipids at
      preconception, upon human chorionic gonadotropin-confirmed pregnancy and
      following pregnancy loss (<14 weeks) or post partum. Pregnancy outcome (loss,
      preterm and term delivery) and gestational length were modeled relative to daily
      rate of change in lipids using multinomial regression and Cox proportional
      hazards models, respectively, adjusting for body mass index and smoking. RESULTS:
      A rate of triglyceride change below the median was associated with an increased
      risk for pregnancy loss compared with term birth (adjusted odds ratio: 9.02; 95%
      CI: 1.62-50.30). A rate of triglyceride change of <=0.01 mg/dl per day versus
      above the median was associated with a trend for increased risk of pregnancy loss
      or preterm (<37 weeks) birth (adjusted hazard ratio: 1.77; 95% CI: 0.94-3.33).
      CONCLUSION: A low rate of triglyceride change during early pregnancy may be a
      signal of risk of pregnancy loss or preterm birth. Lipids offer promise for
      identifying pregnancies at risk for adverse outcomes.

PMID- 24334827
TI  - Frequency of neurotic symptoms shortly after the death of a pet.
AB  - Some individuals manifest psychosomatic symptoms after the death of their pets. A
      survey was conducted at four public and commercial animal cremation service
      centers in Japan. In each center, a questionnaire was distributed to 100
      individuals (400 in total). The questionnaire consisted of the 28-item version of
      the General Health Questionnaire (GHQ28), the social readjustment rating scale
      (SRRS) and a series of questions regarding demographic information and the
      circumstances of their pet's death. In total, 82 returned questionnaires were
      available for analysis. GHQ28 proved the existence of neurotic symptoms in 46
      responses (56.1%; 95% confidence interval: 44.7%-67.0%). Analysis of the
      responses using the GHQ28 subscales with a Likert scoring system demonstrated
      more somatic dysfunction in females (GHQ-A: P=0.04). Furthermore, significant
      correlations were identified among the following factors: owner's age (GHQ-A:
      rho=-0.60, P=0.01; GHQ-B: rho=-0.29, P=0.01; GHQ-C: rho=-0.32, P<0.01; GHQ-D:
      rho=-0.42, P<0.01), SRRS score (GHQ-A: rho=0.32, P<0.01; GHQ-B: rho=0.25, P=0.02;
      GHQ-D: rho=0.30, P=0.01) and animal's age (GHQ-D: rho=-0.26, P=0.02). The death
      of indoor pets caused deeper depression (GHQ-D: P=0.01) than that of outdoor or
      visiting pets. The results revealed neurotic symptoms in almost half of the pet
      owners shortly after their pet's death. 

PMID- 24334828
TI  - Vertebral formula in red-crowned crane (Grus japonensis) and hooded crane (Grus
      monacha).
AB  - Red-crowned cranes (Grus japonensis) are distributed separately in the east
      Eurasian Continent (continental population) and in Hokkaido, Japan (island
      population). The island population is sedentary in eastern Hokkaido and has
      increased from a very small number of cranes to over 1,300, thus giving rise to
      the problem of poor genetic diversity. While, Hooded cranes (Grus monacha), which
      migrate from the east Eurasian Continent and winter mainly in Izumi, Kagoshima
      Prefecture, Japan, are about eight-time larger than the island population of Red
      crowned cranes. We collected whole bodies of these two species, found dead or
      moribund in eastern Hokkaido and in Izumi, and observed skeletons with focus on
      vertebral formula. Numbers of cervical vertebrae (Cs), thoracic vertebrae (Ts),
      vertebrae composing the synsacrum (Sa) and free coccygeal vertebrae (free Cos) in
      22 Red-crowned cranes were 17 or 18, 9-11, 13 or 14 and 7 or 8, respectively.
      Total number of vertebrae was 47, 48 or 49, and the vertebral formula was divided
      into three types including 9 sub-types. Numbers of Cs, Ts, vertebrae composing
      the Sa and free Cos in 25 Hooded cranes were 17 or 18, 9 or 10, 12-14 and 6-8,
      respectively. Total number of vertebrae was 46, 47, 48 or 49, and the vertebral
      formula was divided into four types including 14 sub-types. Our findings clearly
      showed various numerical vertebral patterns in both crane species; however, these
      variations in the vertebral formula may be unrelated to the genetic diversity. 

PMID- 24334829
TI  - The silicon concentration in cat urine and its relationship with other elements.
AB  - To understand the effects of silicon (Si) in the urine with respect to the
      formation of urinary stones, the distribution of Si in urine was observed. Urine
      samples from cats with urolithiasis (n=10) and healthy cats (n=15) were used. The
      concentration of Si in the cats with urolithiasis was significantly higher
      (P<0.001). A significant correlation (P<0.05) was observed between the
      concentration of Si and those of other elements, such as calcium, magnesium,
      phosphorus, potassium and iron, only in the urine of the healthy cats. The
      distribution of elements in the urine differed between the cats with urolithiasis
      and the healthy cats. The Si concentration and its relationship with other
      elements were suggested to be useful biomarkers for urolithiasis in cats. 

PMID- 24334830
TI  - Reply: To PMID 23948802.

PMID- 24334832
TI  - Microbial reduction in wastewater treatment using Fe(3+) and Al(3+) coagulants
      and PAA disinfectant.
AB  - Wastewater is an important source of pathogenic enteric microorganisms in surface
      water and a major contaminating agent of drinking water. Although primary and
      secondary wastewater treatments reduce the numbers of microorganisms in
      wastewater, significant numbers of microbes can still be present in the effluent.
      The aim of this study was to test the feasibility of tertiary treatment for
      municipal wastewater treatment plants (WWTPs) using PIX (FeCl3) or PAX (AlCl3)
      coagulants and peracetic acid (PAA) the disinfectant to reduce microbial load in
      effluent. Our study showed that both PIX and PAX efficiently reduced microbial
      numbers. PAA disinfection greatly reduced the numbers of culturable indicator
      microorganisms (Escherichia coli, intestinal enterococci, F-specific RNA
      coliphages and somatic DNA coliphages). In addition, pathogenic microorganisms,
      thermotolerant Campylobacter, Salmonella and norovirus GI, were successfully
      reduced using the tertiary treatments. In contrast, clostridia, Legionella,
      rotavirus, norovirus GII and adenovirus showed better resistance against PAA
      compared to the other microorganisms. However, interpretation of polymerase chain
      reaction (PCR) analysis results will need further studies to clarify the
      infectivity of the pathogenic microbes. In conclusion, PIX and PAX flocculants
      followed by PAA disinfectant can be used as a tertiary treatment for municipal
      WWTP effluents to reduce the numbers of indicator and pathogenic microorganisms. 

PMID- 24334833
TI  - Cationic, anionic and neutral dyes: effects of photosensitizing properties and
      experimental conditions on the photodynamic inactivation of pathogenic bacteria.
AB  - The aim of this study was to evaluate the photobactericidal effect of four
      photosensitizers (PSs) with different structural and physico-photochemical
      properties, namely mesotetracationic porphyrin (T4MPyP), dianionic rose Bengal
      (RB), monocationic methylene blue (MB) and neutral red (NR). Their photokilling
      activity was tested in vitro on pathogenic bacteria such as Pseudomonas
      aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) suspended in
      nutrient broth (NB) and in phosphate buffered saline (PBS) through following
      their influence on the PSs antimicrobial efficacy. Photodynamic inactivation
      (PDI) experiments were performed using visible light (L) and different PSs
      concentrations (20-70 MUM). The ability of these PSs to mediate bacterial
      photodynamic inactivation was investigated as a function of type of PS and its
      concentrations, spectral and physico-chemical properties, bacterial strain,
      irradiation time and suspending medium. Indeed, they showed antibacterial effects
      against S. aureus and P. aeruginosa with significant difference in potency.
      Staphylococcus aureus suspended in NB showed 0.92 log units reduction in viable
      count in the presence of T4MPyP at 20 MUM. Changing the suspending medium from NB
      to PBS, S. aureus was successfully photoinactivated by T4MPyP (20 MUM) when
      suspended in PBS at least time exposure (10 and 30 min), followed by MB and RB. 

PMID- 24334831
TI  - Cholesterol: the good, the bad, and the ugly - therapeutic targets for the
      treatment of dyslipidemia.
AB  - Maintaining cholesterol and triglyceride (TG) levels within healthy limits is
      critical for decreasing the risk of heart disease. Dyslipidemia refers to the
      abnormal levels of lipids in the blood, including low high-density lipoprotein
      cholesterol (HDL-C), also known as good cholesterol, high low-density lipoprotein
      cholesterol (LDL-C), also known as bad cholesterol, and/or high TG levels that
      contribute to the development and progression of atherosclerosis. In this article
      we reviewed some of the current therapeutic targets for the treatment of
      dyslipidemia, with a primary focus on endothelial lipase and lecithin cholesterol
      acyl transferase for raising HDL-C, and the proprotein convertase subtilisin-like
      kexin type 9 (PCSK9), microsomal triglyceride transfer protein, and the messenger
      RNA of apolipoprotein B for lowering LDL-C. In addition, we reviewed the role of
      apolipoprotein AI (apoAI) in raising HDL-C, where we discuss three apoAI-based
      drugs under development. These are its mutated dimer (apoAI-Milano), a complex
      with phospholipids, and a mimetic peptide. Atherosclerosis, mainly because of
      dyslipidemia, is a leading cause of cardiovascular disease. Regarding the title
      of this article, the 'good' refers to HDL-C, the 'bad' refers to LDL-C, and the
      'ugly' refers to atherosclerosis.

PMID- 24334834
TI  - Resistance of Escherichia coli and Enterococcus spp. to selected antimicrobial
      agents present in municipal wastewater.
AB  - In this study, the susceptibility to erythromycin (E) and to
      trimethoprim/sulfamethoxazole (SXT) among isolates of Enterococcus spp. and
      Escherichia coli was tested, respectively. Both fecal indicators were detected
      and isolated from raw (RW) and treated wastewater (TW) as well as from samples of
      activated sludge (AS) collected in a local wastewater treatment plant (WWTP).
      Biodiversity of bacterial community in AS was also monitored using polymerase
      chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Additionally,
      distribution of sul1-3 genes conferring sulfonamide resistance was tested among
      SXT-resistant E. coli. Simultaneously, basic physicochemical parameters and
      concentrations of eight antimicrobial compounds (belonging to folate pathway
      inhibitors and macrolides class) were analyzed in RW and TW samples. Six of the
      selected antimicrobial agents, namely: erythromycin, clarithromycin,
      trimethoprim, roxithromycin, sulfamethoxazole, and N-acetyl-sulfamethoxazole were
      detected in the wastewater samples. Bacterial biodiversity of AS samples were
      comparable with no relevant differences. Among tested Enterococcus spp., E
      resistant isolates constituted 41%. SXT resistance was less prevalent in E. coli
      with 11% of isolates. The genes conferring resistance to sulfonamides (sul1-3)
      were detected in SXT-resistant E. coli of wastewater origin with similar
      frequencies as in other environmental compartments, including clinical ones. 

PMID- 24334835
TI  - Quantitative characterization of the inhibitory effects of salt, humic acid, and
      heavy metals on the recovery of waterborne norovirus by electropositive filters.
AB  - The virus adsorption-elution technique (VIRADEL) using electropositively charged
      filters is used frequently for recovering enteric viruses from water. The filter
      absorbed virus is typically eluted, concentrated, and subsequently detected by
      culture or molecular methods. Human norovirus (HuNoV), one of the most important
      waterborne pathogens, cannot be cultivated by conventional culture methods and is
      typically detected using a reverse transcriptase-polymerase chain reaction (RT
      PCR) assay. However, it is plausible that various inhibitors could be
      concentrated simultaneously during the VIRADEL process and affect RT-PCR assays.
      In this study, we evaluated the effect of typical inhibitors, including humic
      acid, heavy metals, and salt, on the recovery of norovirus by two different
      electropositive filters: 1MDS and Nanoceram. Known amounts of HuNoV and murine
      norovirus were inoculated in 1 L of surface water containing various
      concentrations of humic acid, heavy metals (cadmium and lead), or NaCl. Our
      results indicate that the presence of heavy metals or salt significantly reduced
      the recovery of virus from the electropositive filters. Thus, care should be
      taken when analyzing waterborne norovirus using electropositive filters in
      environments with high concentrations of heavy metal inhibitors or salts. 

PMID- 24334836
TI  - Uptake of household disinfection kits as an additional measure in response to a
      cholera outbreak in urban areas of Haiti.
AB  - Medecins Sans Frontieres-Operational Centre Amsterdam piloted the distribution of
      household disinfection kits (HDKs) and health promotion sessions for cholera
      prevention in households of patients admitted to their cholera treatment centres
      in Carrefour, Port au Prince, Haiti, between December 2010 and February 2011. We
      conducted a follow-up survey with 208 recipient households to determine the
      uptake and use of the kits and understanding of the health promotion messages. In
      61% of surveyed households, a caregiver had been the recipient of the HDK and
      57.7% of households had received the HDKs after the discharge of the patient.
      Among surveyed households, 97.6% stated they had used the contents of the HDK
      after receiving it, with 75% of these reporting using five or more items, with
      the two most popular items being chlorine and soap. A significant (p < 0.05)
      increase in self-reported use items in the HDK was observed in households that
      received kits after 24 January 2011 when the education messages were
      strengthened. To our knowledge, this is the first time it has been demonstrated
      that during a large-scale cholera outbreak, the distribution of simple kits, with
      readily available cleaning products and materials, combined with health promotion
      is easy, feasible, and valued by the target population. 

PMID- 24334837
TI  - Fate of Salmonella Typhimurium in laboratory-scale drinking water biofilms.
AB  - Investigations were carried out to evaluate and quantify colonization of
      laboratory-scale drinking water biofilms by a chromosomally green fluorescent
      protein (gfp)-tagged strain of Salmonella Typhimurium. Gfp encodes the green
      fluorescent protein and thus allows in situ detection of undisturbed cells and is
      ideally suited for monitoring Salmonella in biofilms. The fate and persistence of
      non-typhoidal Salmonella in simulated drinking water biofilms was investigated.
      The ability of Salmonella to form biofilms in monoculture and the fate and
      persistence of Salmonella in a mixed aquatic biofilm was examined. In monoculture
      S. Typhimurium formed loosely structured biofilms. Salmonella colonized
      established multi-species drinking water biofilms within 24 hours, forming micro
      colonies within the biofilm. S. Typhimurium was also released at high levels from
      the drinking water-associated biofilm into the water passing through the system.
      This indicated that Salmonella could enter into, survive and grow within, and be
      released from a drinking water biofilm. The ability of Salmonella to survive and
      persist in a drinking water biofilm, and be released at high levels into the flow
      for recolonization elsewhere, indicates the potential for a persistent health
      risk to consumers once a network becomes contaminated with this bacterium. 

PMID- 24334838
TI  - Effects of a 20 year rain event: a quantitative microbial risk assessment of a
      case of contaminated bathing water in Copenhagen, Denmark.
AB  - Quantitative microbial risk assessments (QMRAs) often lack data on water quality
      leading to great uncertainty in the QMRA because of the many assumptions. The
      quantity of waste water contamination was estimated and included in a QMRA on an
      extreme rain event leading to combined sewer overflow (CSO) to bathing water
      where an ironman competition later took place. Two dynamic models, (1) a drainage
      model and (2) a 3D hydrodynamic model, estimated the dilution of waste water from
      source to recipient. The drainage model estimated that 2.6% of waste water was
      left in the system before CSO and the hydrodynamic model estimated that 4.8% of
      the recipient bathing water came from the CSO, so on average there was 0.13% of
      waste water in the bathing water during the ironman competition. The total
      estimated incidence rate from a conservative estimate of the pathogenic load of
      five reference pathogens was 42%, comparable to 55% in an epidemiological study
      of the case. The combination of applying dynamic models and exposure data led to
      an improved QMRA that included an estimate of the dilution factor. This approach
      has not been described previously. 

PMID- 24334839
TI  - Improving water quality communications at beaches: input from stakeholders.
AB  - OBJECTIVES: Water quality communication practices vary widely and stakeholder
      input has not played a role in defining acceptable levels of risk. Although the
      2012 Recreational Water Quality Criteria (RWQC) emphasize the importance of
      promptly notifying the public about hazardous conditions, little is known about
      the public's understanding of notifications, or about levels of risk deemed
      acceptable. We sought to address these gaps. METHODS: A mixed methods approach
      was used. Focus groups (FGs) provided qualitative data regarding the
      understanding of surface water quality, awareness, and use, of currently
      available water quality information, and acceptability of risk. Intercept
      interviews (INTs) at recreation sites provided quantitative data. RESULTS: INTs
      of 374 people and 15 FG sessions were conducted. Participants had limited
      awareness about water quality information posted at beaches, even during swim
      bans and advisories. Participants indicated that communication content should be
      current, from a trusted source, and describe health consequences. Communicating
      via mobile electronics should be useful for segments of the population. Risk
      acceptability is lower with greater outcome severity, or if children are
      impacted. CONCLUSIONS: Current water quality communications approaches must be
      enhanced to make notification programs more effective. Further work should build
      on this initial effort to evaluate risk acceptability among US beachgoers.

PMID- 24334840
TI  - Detection and characterization of human pathogenic viruses circulating in
      community wastewater using multi target microarrays and polymerase chain
      reaction.
AB  - Sewage pollution remains the most significant source of human waterborne
      pathogens. This study describes the detection and characterization of human
      enteric viruses in community wastewaters using cell culture coupled with multiple
      target microarrays (with a total of 780 unique probes targeting 27 different
      groups of both DNA and RNA viruses) and polymerase chain reaction (PCR) assays.
      Over a 13-month sampling period, RNA viruses (astroviruses and enteroviruses)
      were more frequently detected compared to DNA viruses (adenoviruses, particularly
      type 41 and BK polyomavirus). Overall, many more viruses were shed during the
      winter months (December-February) compared to the summer months. Exploration of
      the multiple types of enteric viruses particularly in winter months identified
      much more significant prevalence of key viral pathogens associated with sewage
      pollution of the water environment than previously realized and seasonal
      disinfection used in some parts of the world may lead to a seeding of ambient
      waters. Molecular characterization of pathogenic viruses in community wastewater
      will improve the understanding of the potential risk of waterborne disease
      transmission of viral pathogens. 

PMID- 24334841
TI  - Estimating effects of improved drinking water and sanitation on cholera.
AB  - Demand for adequate provision of drinking-water and sanitation facilities to
      promote public health and economic growth is increasing in the rapidly urbanizing
      countries of the developing world. With a panel of data on Asia and Africa from
      1990 to 2008, associations are estimated between the occurrence of cholera
      outbreaks, the case rates in given outbreaks, the mortality rates associated with
      cholera and two disease control mechanisms, drinking-water and sanitation
      services. A statistically significant and negative effect is found between
      drinking-water services and both cholera case rates as well as cholera-related
      mortality rates. A relatively weak statistical relationship is found between the
      occurrence of cholera outbreaks and sanitation services. 

PMID- 24334842
TI  - Detection of vanA and vanB genes in vancomycin-resistant enterococci (VRE) from
      groundwater using multiplex PCR analysis.
AB  - A total of 22 groundwater samples were randomly collected from three rural
      communities in the Mafikeng area. Bile esculin agar was used for selective
      isolation of enterococci. Standard preliminary tests (Gram staining, oxidase
      test, catalase test) and confirmatory tests (ProlexTM Streptococcal Grouping
      Rapid Latex Agglutination test kit) were used to determine the identities of
      presumptive enterococci. The antibiotic sensitivity test was performed on all
      positively identified enterococci; percentage resistance and multiple antibiotic
      resistance (MAR) phenotypes were generated. Multiplex polymerase chain reaction
      (PCR) was performed to detect vanA and vanB genes vancomycin-resistant
      enterococci (VRE). A total of 179 enterococci were positively identified and the
      proportion of isolates from Dibate (62.5%) was higher compared to those from
      Majemantsho and Motlhabeng (22.3 and 15.0, respectively). A large proportion
      (81.5 to 100%) of the isolates from Dibate, Motlhabeng and Majemantsho were
      resistant to ampicillin, vancomycin and penicillin G. Two main MAR phenotypes, PG
      VA-Ap-A-OX and PG-VA-Ap-OX, were identified. Multiplex PCR analysis of 50 VRE
      indicated that 17 (34%) were positive for vanA and vanB genes. This highlights
      the need to determine the cause of vancomycin resistance in enterococci in the
      sampled sites and suggests that sequence analysis be used to confirm the
      identities of these amplicons. 

PMID- 24334843
TI  - Comparison of extracts and toxicities of organic compounds in drinking water
      concentrated by single and composite XAD resins.
AB  - We compared extracts and toxicities of organic compounds (OCs) in drinking water
      concentrated by composite XAD-2/8 resin (mixed with an equal volume of XAD-2 and
      XAD-8 resins) with those extracted by single XAD-2 (non-polar) and XAD-8 (polar)
      resins. Drinking water was processed from raw water of the Han River and the
      Yangtze River in Wuhan section, China. The extraction efficiency of all resins
      was controlled at 30%. The types of extracted OCs were detected by gas
      chromatography-mass spectrometry, and the cytotoxicity and genotoxicity were
      assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
      and comet assays, respectively, in human hepatoma HepG2 cells. Our results showed
      that XAD-2/8 extracted a larger variety of OCs, compared with XAD-8 and XAD-2.
      The cytotoxicity and genotoxicity of extracted OCs were in the order of XAD-8>
      XAD-2/8> XAD-2 at almost all tested concentrations after 24 h treatment (P <
      0.05). Our findings suggest that single XAD resin selectively extracts either
      polar or non-polar OCs, which would lead to over- or under-estimation of the
      toxicity of drinking water. Nevertheless, composite resin extracts both polar and
      non-polar OCs, and could be utilized as a useful extraction technique to evaluate
      the level and toxicity of OCs in drinking water. 

PMID- 24334844
TI  - Relationship of aquatic environmental factors with the abundance of Vibrio
      cholerae, Vibrio parahaemolyticus, Vibrio mimicus and Vibrio vulnificus in the
      coastal area of Guaymas, Sonora, Mexico.
AB  - Members of the genus Vibrio are common in aquatic environments. Among them are V.
      cholerae, V. vulnificus, V. parahaemolyticus and V. mimicus. Several studies have
      shown that environmental factors, such as temperature, salinity, and dissolved
      oxygen, are involved in their epidemiology. Therefore, the main objective of this
      study is to determine if there is a correlation between the presence/amount of V.
      cholerae, V, vulnificus, V. parahaemolyticus and V. mimicus and the environmental
      conditions of the seawater off the coast of Guaymas, Mexico. Quantification of
      all four pathogenic bacteria was performed using the most probable number method,
      and suspected colonies were identified by polymerase chain reaction (PCR).
      Correlations were found using principal component analysis. V. parahaemolyticus
      was the most abundant and widely distributed bacteria, followed by V. vulnificus,
      V. mimicus and V. cholerae. Positive correlations between V. parahaemolyticus, V.
      vulnificus and V. mimicus with temperature, salinity, electric conductivity, and
      total dissolved solids were found. The abundance of V. cholerae was mainly
      affected by the sampling site and not by physicochemical parameters. 

PMID- 24334845
TI  - Surveillance of Legionella species in hospital water systems: the significance of
      detection method for environmental surveillance data.
AB  - Monitoring of hospital water systems to prevent and control nosocomial
      legionellosis is important from a public health perspective. This study was
      conducted to survey the prevalence of Legionella contamination of hospital
      waters. A total of 44 water samples from the hot-water system of 11 hospitals
      were tested for Legionella by a culture method and a nested polymerase chain
      reaction (PCR) assay with Legionella-specific primers to identify the more
      sensitive method. Some physicochemical parameters and heterotrophic plate counts
      of water samples for possible association with Legionella contamination were also
      determined. The contamination rate of hospitals in our study varied between 64%
      (eight of 11)-100% based on culture method and nested PCR, respectively. Of the
      44 water samples examined, 23% were positive for Legionella spp. by the culture
      method, while the nested PCR assay using the primers LEG448-JRP revealed 66% of
      the water samples being positive. Given the importance of monitoring hospital
      water systems for the presence of Legionella spp., the present PCR assay proved
      highly applicable for practical and sensitive surveillance of Legionella in such
      water systems. In addition, rapid monitoring of Legionella contamination could
      eliminate the potential exposure of high-risk patients through effective control
      measures. 

PMID- 24334846
TI  - Seasonal and sex-related variations in serum steroid hormone levels in wild and
      farmed brown trout Salmo trutta L. in the north-west of Spain.
AB  - Serum steroid profiles were investigated in order to evaluate the potential use
      of circulating sex steroid levels as a tool for sex identification in brown
      trout. Changes in the serum concentrations of testosterone (T), progesterone (P),
      17-beta-estradiol (E2), and cortisol (F) in wild and farmed mature female and
      male brown trout, Salmo trutta L., were measured in each season (January, May,
      July, and October) in six rivers and four hatcheries located in the north-west of
      Spain. Serum cortisol levels in farmed brown trout were significantly higher and
      showed a seasonal pattern opposite to that found in wild trout. Because levels of
      the hormones under study can be affected by disruptive factors such as exposure
      to phytoestrogens (which alters the hypothalamic-pituitary-gonadal axis) and
      infection with Saprolegnia parasitica (which alters the hypothalamic-pituitary
      adrenal axis), both factors are taken into account. 

PMID- 24334847
TI  - Field comparison of solar water disinfection (SODIS) efficacy between glass and
      polyethylene terephalate (PET) plastic bottles under sub-Saharan weather
      conditions.
AB  - Concerns about photodegradation products leaching from plastic bottle material
      into water during solar water disinfection (SODIS) are a major psychological
      barrier to increased uptake of SODIS. In this study, a comparison of SODIS
      efficacy using glass and plastic polyethylene terephalate (PET) bottles was
      carried out under strong real sunlight and overcast weather conditions at
      Makerere University in central Uganda. Both clear and turbid natural water
      samples from shallow wells and open dug wells, respectively, were used. Efficacy
      was determined from the inactivation of a wild strain of Escherichia coli in
      solar-exposed contaminated water in both glass and PET bottles. The studies
      reveal no significant difference in SODIS inactivation between glass and PET
      bottles (95% CI, p > 0.05), for all water samples under the different weather
      conditions except for clear water under overcast conditions where there was a
      small but significant difference (95% CI, p = 0.047) with less viable bacterial
      counts in PET bottles at two intermediate time points but not at the end of the
      exposure. The results demonstrate that SODIS efficacy in glass under tropical
      field conditions is comparable to PET plastic. SODIS users in these regions can
      choose either of reactors depending on availability and preference of the user. 

PMID- 24334848
TI  - Monochloramine and chlorine dioxide for controlling Legionella pneumophila
      contamination: biocide levels and disinfection by-product formation in hospital
      water networks.
AB  - Legionella colonization in hospital hot water distribution networks was evaluated
      following 36 months of continuous treatment with monochloramine and compared with
      chlorine dioxide. Nitrite, nitrate, chlorite, chlorate, bromide, trihalomethanes
      and haloacetic acids as well as the biocide concentration at sampled points were
      measured. Only 8/84 samples treated with monochloramine were found contaminated
      and after the first 8 months of treatment no Legionella was isolated. Chlorine
      dioxide was associated with a strong reduction in Legionella contamination
      compared to pre-treatment, but differences according to the device were observed.
      Monochloramine between 2 and 3 mg l(-1) and chlorine dioxide between 0.50 and
      0.70 mg l(-1) were needed to control Legionella colonization. Comparing no- and
      post-flush samples, a higher frequency of no-flush positive samples was noted
      using chlorine dioxide, suggesting an increased risk for patients when they open
      the tap. No increase in chlorite levels and no water nitrification occurred by
      using monochloramine. Chlorite at levels exceeding the limit requested for
      drinking water was measured when chlorine dioxide was applied. In conclusion, we
      highlight that continuous injection of monochloramine should be considered as an
      effective alternative to chlorine dioxide in controlling legionellae
      contamination inside hospital water distribution systems. 

PMID- 24334849
TI  - Is drinking water from 'improved sources' really safe? A case study in the Logone
      valley (Chad-Cameroon).
AB  - Within a cooperation project coordinated by the Association for Rural Cooperation
      in Africa and Latin America (ACRA) Foundation, water supplies were sampled across
      the villages of the Logone valley (Chad-Cameroon) mostly from boreholes, open
      wells, rivers and lakes as well as from some piped water. Microbiological
      analyses and sanitary inspections were carried out at each source. The
      microbiological quality was determined by analysis of indicators of faecal
      contamination, Escherichia coli, Enterococci and Salmonellae, using the membrane
      filtration method. Sanitary inspections were done using WHO query forms. The
      assessment confirmed that there are several parameters of health concern in the
      studied area; bacteria of faecal origins are the most significant. Furthermore,
      this study demonstrated that Joint Monitoring Programme (JMP) classification and
      E. coli measurement are not sufficient to state water safety. In fact, in the
      studied area, JMP defined 'improved sources' may provide unsafe water depending
      on their structure and sources without E. coli may have Enterococci and
      Salmonellae. Sanitary inspections also revealed high health risks for some
      boreholes. In other cases, sources with low sanitary risk and no E. coli were
      contaminated by Enterococci and Salmonellae. Better management and protection of
      the sources, hygiene improvement and domestic water treatment before consumption
      are possible solutions to reduce health risks in the Logone valley. 

PMID- 24334850
TI  - Typing of Legionella strains isolated from environmental samples in Crete,
      Greece, during the period 2004-2011.
AB  - In Greece, standard tests are performed in watering and cooling systems of
      hotels. A total of 1,494 water samples were collected during 2004-2011 from 124
      hotels from four regions in Crete (Greece). Samples were tested for the presence
      of Legionella spp.; 103 isolates were identified and typed by polymerase chain
      reaction (PCR)-sequencing and sequence-based typing (SBT) (in case of L.
      pneumophila sg 1). Of those, 48 belonged to various serogroups of L. pneumophila
      (sg 1, 2, 3, 5, 6, 8, 12, 13, and 15), 32 were characterized as L. anisa, 17 as
      L. taurinensis and there was a single occurrence of L. quinlivanii, L.
      maceachernii, and L. oakridgensis. In the case of L. pneumophila SG1, one
      prevalent sequence type was revealed (ST37). The variability of Legionella spp.
      observed questions the existence of a single ST of the L. pneumophila sg1 species
      and leads towards the need for a genetic level investigation of all Legionnaires'
      disease cases. 

PMID- 24334851
TI  - Detection of enteric viruses in Hungarian surface waters: first steps towards
      environmental surveillance.
AB  - Waterborne viruses infect the human population through the consumption of
      contaminated drinking water and by direct contact with polluted surface water
      during recreational activity. Although water related viral outbreaks are a major
      public health concern, virus detection is not a part of the water quality
      monitoring scheme, mainly due to the absence of routine analysis methods. In the
      present study, we implemented various approaches for water concentration and
      virus detection, and tested on Hungarian surface water samples. Eighty samples
      were collected from 16 sites in Hungary. Samples were concentrated by glass wool
      and membrane filtration. Human adenoviruses were detected by conventional and
      quantitative real-time polymerase chain reaction (PCR) methods in 56% (45/80) of
      the samples; viral titers ranged from 8.60 * 10(1) to 3.91 * 10(4) genome copies
      per liter. Noroviruses and enteroviruses were detected in 30% (24/80) and 13%
      (10/80) of samples, respectively, by reverse transcription-PCR assays. Results
      indicate a high prevalence of viral human pathogens in surface waters, suggesting
      the necessity of a detailed survey focusing on the quality of natural bathing
      waters and drinking water sources. 

PMID- 24334852
TI  - Annexin 7 in the regulation of gastric acid secretion.
AB  - BACKGROUND/AIMS: Glucocorticoids enhance gastric acid secretion and inhibit
      gastric cyclooxygenase, thus downregulating formation of PGE2, an inhibitor of
      gastric acid secretion. In erythrocytes, PGE2 formation is inhibited by annexin
      7. The present study thus explored whether annexin 7 participates in the
      regulation of gastric acid secretion. METHODS: Annexin 7 protein expression was
      determined by Western blotting, cytosolic pH (pHi) of parietal cells utilizing
      BCECF-fluorescence, and gastric acid secretion by determination of Na(+)
      independent pHi recovery from an ammonium pulse (?pHi/min). Experiments were
      performed in isolated glands from gene targeted mice lacking annexin 7 (anx7(-/
      )) and in respective wild type animals (anx7(+/+)). RESULTS: Prior to treatment
      pHi and ?pHi/min were similar in isolated gastric glands from anx7(-/-) and from
      anx7(+/+) mice. Aspirin (100 uM added to the glands 1 hr prior to the experiment)
      significantly increased ?pHi/min to similar values in both genotypes. The
      administration of dexamethasone (10 ug/g BW subcutaneously for 4 consecutive days
      prior to the experiments) significantly increased ?pH/min in anx7(+/+) mice but
      not in anx7(-/-) mice. Following dexamethasone treatment, the luminal pH was
      significantly lower and the acid content significantly higher in anx7(+/+) mice
      than in anx7(-/-) mice. An increase of extracellular K(+) concentration to 35 mM
      (replacing Na(+)/NMDG(+)) significantly increased ?pHi/min in both genotypes. In
      neither genotype dexamethasone increased ?pH/min further in the presence of 35 mM
      K(+) or presence of aspirin. CONCLUSIONS: Annexin 7 is required for the
      stimulation of gastric acid secretion by glucocorticoids.

PMID- 24334853
TI  - Functional coronary stenosis severity assessed from the mean pressure gradient
      velocity relationship obtained by contrast medium-induced submaximal hyperaemia.
AB  - AIMS: First, to establish the diagnostic performance of the pressure gradient at
      a standardised mean velocity (dPv) as derived from the cycle-averaged stenosis
      pressure gradient-velocity (dP-v) relationship obtained by administration of
      adenosine and, second, to determine whether dPv can be assessed from contrast
      medium-induced submaximal hyperaemia. METHODS AND RESULTS: Distal coronary
      pressure and velocity were simultaneously recorded in 64 patients during the
      response to intracoronary injection of adenosine. dPv was assessed at velocities
      between 20 and 50 cm/s. The pressure gradient at a mean flow velocity of 30 cm/s
      (dPv30) yielded an excellent diagnostic performance against FFR <=0.8 (area under
      the curve 0.96; sensitivity 84%; specificity 96%; accuracy 89%). In a subgroup of
      21 patients, measurements were repeated throughout contrast medium-induced
      reactive hyperaemia. Peak velocity and pressure gradient were lower compared to
      adenosine, but the course of the corresponding dP-v relationships coincided very
      well over the common velocity range, with no difference in dPv30. CONCLUSIONS:
      dPv30 reliably detects functionally significant coronary lesions. It derives from
      stenosis haemodynamics and can be obtained with submaximal hyperaemia, such as
      following injection of contrast medium, thereby obviating the maximal
      vasodilation by adenosine required for FFR or other established hyperaemic
      parameters of functional stenosis severity.

PMID- 24334854
TI  - Cost analysis of an intravenous to subcutaneous epoetin alpha conversion.
AB  - BACKGROUND/AIMS: A cost analysis of a conversion from intravenous (IV) to
      subcutaneous (SC) epoetin alpha in patients receiving chronic in-center
      hemodialysis (HD). METHODS: This retrospective analysis compared epoetin alpha
      drug costs during a 6-month period of IV usage (July to December 2010, period 1)
      to a 6-month period of SC usage (July to December 2011, period 2) in four large
      in-center HD units. Data were collected from quarterly counts of HD patients
      receiving epoetin alpha and monthly inventory billing records. RESULTS: 622 HD
      patients who received IV epoetin alpha (period 1) were compared to 609 HD
      patients who received SC epoetin alpha (period 2). A 12.6% decrease in dose was
      observed. The average weekly cost of epoetin alpha was USD 173.02 per patient
      during the IV period versus USD 151.20 per patient during the SC period. This
      equated to a yearly cost savings of USD 1,135 per patient with SC epoetin alpha.
      CONCLUSION: The switch from IV to SC epoetin alpha was successfully implemented
      in all four centers and realized significant cost savings.

PMID- 24334855
TI  - Visual detection of canine parvovirus based on loop-mediated isothermal
      amplification combined with enzyme-linked immunosorbent assay and with lateral
      flow dipstick.
AB  - Loop-mediated isothermal amplification (LAMP) combined with enzyme-linked
      immunosorbent assay (LAMP-ELISA) and with lateral flow dipstick (LAMP-LFD) are
      rapid, sensitive and specific methods for the visual detection of clinical
      pathogens. In this study, LAMP-ELISA and LAMP-LFD were developed for the visual
      detection of canine parvovirus (CPV). For LAMP, a set of four primers (biotin
      labeled forward inner primers) was designed to specifically amplify a region of
      the VP2 gene of CPV. The optimum time and temperature for LAMP were 60 min and 65
      degrees C, respectively. The specific capture oligonucleotide probes, biotin
      labeled CPV probe for LAMP-ELISA and fluorescein isothiocyanate-labeled CPV probe
      for LAMP-LFD were also designed for hybridization with LAMP amplicons on
      streptavidin-coated wells and LFD strips, respectively. For the comparison of
      detection sensitivity, conventional PCR and LAMP for CPV detection were also
      performed. The CPV detection limits by PCR, PCR-ELISA, LAMP, LAMP-ELISA and LAMP
      LFD were 10(2), 10(2), 10(-1), 10(-1) and 10(-1) TCID50/ml, respectively. In
      tests using artificially contaminated dog fecal samples, the samples with CPV
      inoculation levels of >=1 TCID50/ml gave positive results by both LAMP-ELISA and
      LAMP-LFD. Our data indicated that both LAMP-ELISA and LAMP-LFD are promising as
      rapid, sensitive and specific methods for an efficient diagnosis of CPV
      infection. 

PMID- 24334856
TI  - From palmistry to anthropometry: can 2nd to 4th digit length (2D:4D) predict the
      risk of prostate cancer?
AB  - OBJECTIVE: The 2nd to 4th digit length (2D:4D) is inversely related to androgen
      exposure during the fetal period, which may represent a risk factor for several
      steroid-related diseases. We aimed to evaluate the relationship between 2D:4D
      ratio and the risk of developing prostate cancer (PCa). SUBJECTS AND METHODS: We
      assessed the 2D:4D ratio of 474 men >40 years old, stratified into three groups:
      group 1 (n = 222) patients with PCa, group 2 (n = 82) subjects with high risk of
      PCa, and group 3 (n = 170) men with low risk of PCa. Subjects were submitted to a
      digital picture of the ventral surface of the right hand and 2nd and 4th fingers
      measurements were determined by the distance from the proximal crease to the tip
      using computer-assisted analysis. RESULTS: The mean serum prostate-specific
      antigen level was 7.5 ng/ml in the high-risk group and 0.92 ng/ml in the low-risk
      group (p < 0.05). The mean 2D:4D ratios were 0.96 +/- 0.04, 0.97 +/- 0.04 and
      0.96 +/- 0.04 for the PCa, high-risk and low-risk groups, respectively, and no
      difference was found among the three groups (p = 0.12). CONCLUSION: Anthropometry
      of the hand using the 2D:4D ratio is not a predictor of PCa.

PMID- 24334858
TI  - Antley-Bixler syndrome: surgical management of ambiguous genitalia - a case
      report.
AB  - OBJECTIVE: To report a case of type 2 Antley-Bixler syndrome (ABS). SUBJECT AND
      METHODS: A 3-year-old boy who had been raised male, with facial dimorphism and
      malformations of both elbows and forearms, was referred to our unit for ambiguous
      genitalia. Genetic testing confirmed the diagnosis of ABS. A surgical
      intervention was performed to correct the ambiguous genitalia through a combined
      perineal and transabdominal approach. RESULTS: The postoperative course was
      uneventful and the patient was released from the hospital 10 days after the
      surgery. CONCLUSION: Repair of the ambiguous genitalia in this patient was
      possible, but definitive inferences on the benefit of this intervention cannot be
      made without long-term follow-up.

PMID- 24334857
TI  - Clinical efficacy of autologous plasma therapy for atopic dermatitis.
AB  - BACKGROUND: The clinical efficacy of autologous blood therapy (ABT) in patients
      with atopic dermatitis (AD) was demonstrated by a randomized double-blind placebo
      controlled study. To characterize the blood component mediating the therapeutic
      efficacy of ABT for AD, we evaluated the clinical efficacy of autologous plasma
      therapy (APT) and autologous high-molecular-weight plasma protein fraction
      therapy (AHPT) in patients with AD in this study. METHODS: A total of 22 patients
      with recalcitrant AD were treated with 8 weekly intramuscular injections of
      either autologous plasma (n = 11) or autologous high-molecular-weight plasma
      protein fraction (n = 11) for 7 weeks. RESULTS: The clinical severity score of AD
      (SCORAD value) of 11 patients who completed AHPT significantly decreased from
      79.7 +/- 17.0 (mean +/- SD) at baseline to 65.8 +/- 16.4 at 6 weeks and 60.1 +/-
      16.0 at 7 weeks (Wilcoxon signed-rank test, p < 0.05). There were no significant
      differences among the SCORAD values measured at baseline (74.2 +/- 19.6), at 6
      weeks (66.3 +/- 23.6) and at 7 weeks (67.5 +/- 20.8) in 10 patients who completed
      APT (p > 0.05). CONCLUSION: This result suggests that the blood component
      mediating the therapeutic efficacy of ABT in patients with AD might be present in
      the high-molecular-weight plasma protein fraction.

PMID- 24334859
TI  - Endobronchial valves in the management of recurrent haemoptysis.
AB  - Minimally invasive treatment modalities for life-threatening haemoptysis in
      patients unresponsive to medical interventions and/or in patients deemed
      functionally inoperable are limited. We describe the implantation of
      endobronchial valves in a patient with recurrent haemoptysis, which presents both
      a novel indication for the use of these devices and a novel intervention for
      haemoptysis. Our patient is a 30-year-old male who developed bilateral upper lobe
      aspergillomata following previous pulmonary tuberculosis. The patient had a
      history of multiple hospitalisations for life-threating haemoptysis despite
      repeated bronchial artery embolisations. He was deemed to be inoperable given the
      bilateral nature of his disease and very poor pulmonary reserves. We proceeded to
      identify the segments involved with the aid of computed tomography reconstruction
      and implanted 3 endobronchial valves. Our patient remained haemoptysis free for 6
      months and experienced no stent-related complications. Moreover, he was
      subsequently employed as a manual labourer and showed significant improvements in
      his functional capacity. Endobronchial valves may therefore represent a viable
      medium-term treatment option as a blockade device in patients unresponsive to
      medical interventions and/or in patients deemed functionally inoperable.
      Prospective studies are indicated to better delineate the role of endobronchial
      valves in this setting.

PMID- 24334860
TI  - An exploratory examination of student to professor disclosures of crime
      victimization.
AB  - Prior qualitative research has demonstrated that female college students may
      utilize their professors as support providers when they experience sexual assault
      and intimate partner violence victimization. To further explore this phenomenon,
      the present study used a random sampling design on two college campuses to
      examine the following questions: (a) Are student disclosures of crime
      victimization a common occurrence for college professors? (b) What is the nature
      of college professors' most recent disclosure of crime victimization? and (c) Do
      professor characteristics predict receiving a student disclosure of
      victimization? Implications of these findings as well as directions for future
      research will be discussed. 

PMID- 24334861
TI  - Perceptions of similarity and responsibility attributions to an acquaintance
      sexual assault victim.
AB  - Individuals view similar rape victims as less responsible for the rape than
      victims perceived as dissimilar. However, it is unclear if individuals hold
      victims they perceive as similar less responsible for the assault, or if
      individuals view themselves as more similar to victims they do not view as
      responsible for the assault. The current study, therefore, examined the temporal
      relationship between these constructs. A total of 167 college women listened to a
      date narrative that ended in sexual assault, consensual sex, or no sexual
      activity (these last two served as controls). Results supported that participants
      viewed themselves as less similar to the woman in the narrative when the date
      ended in sexual assault. Only similarity ratings made following learning that the
      woman was sexually assaulted predicted responsibility attributions suggesting
      that viewing a victim as responsible for the assault results in decreased
      perceptions of similarity toward her. Implications and suggestions for future
      research are discussed. 

PMID- 24334862
TI  - Effects of cryopreservation on the cell viability, proliferative capacity and
      neuronal differentiation potential of canine bone marrow stromal cells.
AB  - We investigated the cell viability, proliferative capacity and neuronal
      differentiation potential of canine bone marrow stromal cells (BMSCs) after
      cryopreservation. BMSCs were cryopreserved using cryoprotectant solutions with
      10% DMSO and 10% FBS (DF group) or without DMSO and FBS (DF-free group); fresh
      BMSCs were used as a control. The cell viability and proliferative capacity of
      BMSCs were similar in the DF-free and control groups, while those in the DF group
      were lower. In all groups, BMSCs differentiated into neuron-like cells that
      stained positive against neuron markers, and the mRNA expression levels of neuron
      markers increased after neuronal induction. In conclusion, cryopreservation with
      DF-free cryoprotectant solution did not diminish the cell viability,
      proliferative capacity or neuronal differentiation potential of canine BMSCs. 

PMID- 24334863
TI  - In vitro susceptibility of Malassezia pachydermatis isolates from canine skin
      with atopic dermatitis to ketoconazole and itraconazole in East Asia.
AB  - Topical or oral azole antifungals are commonly used in canine atopic dermatitis
      (AD), as the lipophilic yeast Malassezia pachydermatis exacerbates canine AD. To
      examine whether canine AD lesions harbor azole-resistant M. pachydermatis
      isolates in East Asia, we investigated the in vitro susceptibility of M.
      pachydermatis isolates to ketoconazole (KTZ) and itraconazole (ITZ) obtained from
      AD lesions of canines in Japan, Korea and Taiwan. The minimum inhibitory
      concentrations (MICs) of KTZ and ITZ were measured by the E-test using Sabouraud
      dextrose agar with 0.5% Tween 40. The MICs of KTZ and ITZ for isolates from
      canines with AD were significantly higher than the MICs for isolates from healthy
      canines. Our findings suggested that the clinical isolates from canine AD skin
      lesions were less susceptible to azoles than those from normal canine skin in
      East Asia. 

PMID- 24334864
TI  - Gas chromatography-mass spectrometry-based metabolic profiling of cerebrospinal
      fluid from epileptic dogs.
AB  - Epilepsy is a common neurological disorder with seizures, but diagnostic
      approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a
      body fluid used for diagnosis in veterinary medicine. In this study, we explored
      canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry
      (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles
      for subjects with idiopathic epilepsy differed significantly from those of
      healthy controls and subjects with symptomatic epilepsy. Among 60 identified
      metabolites, the levels of 20 differed significantly among the three groups.
      Glutamic acid was significantly increased in idiopathic epilepsy, and some
      metabolites including ascorbic acid were changed in both forms of epilepsy. These
      findings show that metabolic profiles of CSF differ between idiopathic and
      symptomatic epilepsy and that metabolites including glutamic acid and ascorbic
      acid in CSF may be useful for diagnosis of canine epilepsy. 

PMID- 24334865
TI  - Retrospective analysis of a novel regimen for the prevention of venous
      thromboembolism in nephrotic syndrome.
AB  - BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) occurs in 7%-40% of
      nephrotic patients. The risk of VTE depends on the severity and underlying cause
      of nephrotic syndrome. This study investigated the use of low-dose prophylactic
      anticoagulation to prevent VTE in patients with nephrotic syndrome caused by
      primary glomerulonephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Since
      2006, all patients presenting with nephrotic syndrome to Imperial College Kidney
      and Transplant Centre have been considered for treatment with a novel
      anticoagulation prophylaxis regimen. All cases of nephrotic syndrome secondary to
      primary membranous nephropathy, minimal-change disease, and FSGS over a 5-year
      period were retrospectively reviewed. Patients with serum albumin<2.0 g/dl
      received prophylactic-dose low-molecular-weight heparin or low-dose warfarin;
      patients with albumin levels of 2.0-3.0 g/dl received aspirin, 75 mg once daily.
      All thrombotic events and bleeding complications were recorded. RESULTS: A total
      of 143 patients received the prophylactic anticoagulation regimen. Median follow
      up was 154 weeks (range, 30-298 weeks). The cohort had features associated with a
      high risk of developing VTE; 40% of the cohort had an underlying diagnosis of
      membranous nephropathy, and the initial median serum albumin was 1.5 g/dl (range,
      0.5-2.9 g/dl). No VTE occurred in patients established on prophylaxis for at
      least 1 week. VTE was diagnosed in 2 of 143 patients (1.39%) within the first
      week after presentation and starting prophylaxis. In both cases, it is unclear
      whether the thrombus had developed before or after the start of prophylaxis. One
      of 143 (0.69%) patients receiving prophylaxis was admitted urgently with
      gastrointestinal hemorrhage. Two of 143 patients (1.40%) had elective blood
      transfusions and procedures to manage occult gastrointestinal bleeding. No other
      bleeding events occurred in patients receiving prophylaxis. CONCLUSIONS: This
      regimen of prophylactic antiplatelet or anticoagulant therapy appears effective
      in preventing VTE in nephrotic syndrome, with relatively few hemorrhagic
      complications.

PMID- 24334866
TI  - The role of Kuwait in the development of early thrombus removal in patients with
      acute iliofemoral vein thrombosis: in memory of Dr. Nael Al-Naqeeb.
AB  - Many physicians in Kuwait have contributed to the development of the management
      of acute iliofemoral deep venous thrombosis utilizing open surgical thrombectomy
      for early thrombus removal. This concept is now accepted around the world, with
      new endovascular procedures replacing open surgery. Its development is described
      and the latest guidelines for early thrombus removal are presented.

PMID- 24334868
TI  - Effects of freeze-dried strawberry supplementation on metabolic biomarkers of
      atherosclerosis in subjects with type 2 diabetes: a randomized double-blind
      controlled trial.
AB  - BACKGROUND: To our knowledge there has been no study investigating the impact of
      freeze-dried strawberry (FDS) supplementation on metabolic biomarkers of
      atherosclerosis in subjects with type 2 diabetes (T2D). OBJECTIVE: This study was
      carried out to determine the effects of FDS supplementation on glycemic control,
      biomarkers of oxidative stress, inflammation and serum total antioxidant status
      in subjects with T2D compared to matched control subjects. METHODS: Thirty-six
      subjects with T2D (23 females; mean body mass index 27.90 +/- 3.7; mean age 51.57
      +/- 10 years) were randomly divided into two groups. The treatment group consumed
      2 cups of FDS beverage (50 g of FDS is equivalent to 500 g of fresh strawberries)
      or macronutrient matched placebo powder with strawberry flavor daily for 6 weeks
      in a randomized double-blind controlled trial. Anthropometric measurements,
      dietary intakes, hemoglobin (Hb)A1c, antioxidant status, C-reactive protein and
      malondialdehyde (MDA) levels were assessed at baseline and 6 weeks post
      intervention. RESULTS: FDS supplementation significantly decreased C-reactive
      protein levels as a biomarker of inflammation (2.5 vs. 2.04 mg/l, p < 0.05) and
      lipid peroxidation in the form of MDA (3.36 vs. 2.7 nmol/ml, p < 0.05) at 6 weeks
      compared to the baseline. Moreover, supplementation led to a decreasing trend in
      HbA1c (-5.7%, p < 0.05) and significant increase in total antioxidant status in
      the FDS group (1.44 vs. 1.26 mmol/l, p < 0.01) compared to the placebo group. No
      significant changes were observed in serum glucose concentrations and
      anthropometric indices. CONCLUSIONS: FDS improved glycemic control and
      antioxidant status, and reduced lipid peroxidation and inflammatory response in
      patients with T2D. Supplementation with freeze-dried berry products, as natural
      sources of antioxidants with low glycemic index, could be considered as an
      adjunctive therapy in ameliorating metabolic complications of T2D.

PMID- 24334867
TI  - Impact of TNF haplotypes in the physical course of acne vulgaris.
AB  - BACKGROUND: The role of single-nucleotide polymorphisms (SNPs) of the TNF gene in
      acne vulgaris remains controversial. METHODS: Genomic DNA was isolated from 185
      patients with acne vulgaris and 165 healthy controls. SNPs at positions -376, 
      308 and -238 of the promoter region of TNF were defined. RESULTS: The frequency
      of the GAG haplotype was greater among patients (16.8%) than among controls with
      borderline significance (9.7%, p = 0.059). Male carriers of haplotypes other than
      GGG presented acne vulgaris at a later age than carriers of the GGG haplotype. No
      effect of the GAG haplotype on the frequency of acne conglobata was found among
      women with polycystic ovary syndrome. CONCLUSIONS: Carriage of the GAG haplotype
      of TNF is linked with borderline susceptibility to acne vulgaris. The GGG
      haplotype is related with earlier disease onset in male patients.

PMID- 24334869
TI  - Serum hepcidin is associated with presence of plaque in postmenopausal women of a
      general population.
AB  - OBJECTIVE: Iron and the iron regulatory hormone hepcidin, major determinant of
      body iron distribution, are hypothesized to play a role in cardiovascular
      disease. Here, we assess the associations of hepcidin as well as ferritin, iron,
      total iron-binding capacity, and transferrin saturation (ie, iron parameters)
      with noninvasive measurements of atherosclerosis in men and women of a population
      based cohort. APPROACH AND RESULTS: We included 766 participants of the Nijmegen
      Biomedical Study aged 46 to 67 years for whom serum measurements of hepcidin,
      iron parameters, and noninvasive measurements of atherosclerosis were available.
      Noninvasive measurements of atherosclerosis were presence of plaque, ankle
      brachial index, and intima-media thickness. We performed multivariable logistic
      and linear regression analyses using quartiles of hepcidin and iron parameters.
      Analyses were stratified by sex and adjusted for several demographic, clinical,
      and biochemical determinants, including traditional risk factors of
      cardiovascular disease based on the Framingham risk score. Hepcidin and the
      hepcidin/ferritin ratio, reflecting hepcidin expression relative to iron stores,
      were significantly associated with the presence of plaque in women (adjusted odds
      ratios for quartile 4 versus quartile 1 [95% confidence intervals] of 3.07 [1.36
      6.90] and 2.31 [1.03-5.18], respectively). The hepcidin/ferritin ratio was
      significantly and negatively associated with ankle-brachial index at rest in men
      and women (adjusted beta for quartile 4 versus quartile 1 [95% confidence
      intervals] of -0.03 [-0.07 to 0.00] and -0.04 [-0.06 to -0.01], respectively).
      CONCLUSIONS: Our results suggest that the body iron distribution as determined by
      hepcidin affects the development of atherosclerosis in women.

PMID- 24334870
TI  - A regulator of secretory vesicle size, Kelch-like protein 12, facilitates the
      secretion of apolipoprotein B100 and very-low-density lipoproteins--brief report.
AB  - OBJECTIVE: One of the major risk factors for atherosclerosis is the plasma level
      of low-density lipoprotein (LDL), which is a product of very-low-density
      lipoprotein (VLDL). Hepatic apolipoprotein B100 (apoB100) is the essential
      component that provides structural stability to VLDL particles. Newly translated
      apoB100 is partially lipidated in the endoplasmic reticulum (ER), forming nascent
      apoB100-VLDL particles. These particles are further modified to form fully mature
      VLDLs in the Golgi apparatus. Therefore, the transport of nascent VLDL from the
      ER to the Golgi represents a critical step during VLDL maturation and secretion
      and in regulating serum LDL cholesterol levels. Our previous studies showed that
      apoB100 exits the ER in coat complex II vesicles (COPII), but the cohort of
      related factors that control trafficking is poorly defined. APPROACH AND RESULTS:
      Expression levels of Kelch-like protein 12 (KLHL12), an adaptor protein known to
      assist COPII-dependent transport of procollagen, were manipulated by using a
      KLHL12-specific small interfering RNA and a KLHL12 expression plasmid in the rat
      hepatoma cell line, McArdle RH7777. KLHL12 knockdown decreased the secreted and
      intracellular pools of apoB100, an effect that was attenuated in the presence of
      an autophagy inhibitor. KLHL12 knockdown also significantly reduced secretion of
      the most lipidated apoB100-VLDL species and led to the accumulation of apoB100 in
      the ER. Consistent with these data, KLHL12 overexpression increased apoB100
      recovery and apoB100-VLDL secretion. Images obtained from confocal microscopy
      revealed colocalization of apoB100 and KLHL12, further supporting a direct link
      between KLHL12 function and VLDL trafficking from the ER. CONCLUSIONS: KLHL12
      plays a critical role in facilitating the ER exit and secretion of apoB100-VLDL
      particles, suggesting that KLHL12 modulation would influence plasma lipid levels.

PMID- 24334871
TI  - P21-dependent protective effects of a carbon monoxide-releasing molecule-3 in
      pulmonary hypertension.
AB  - OBJECTIVE: Carbon monoxide-releasing molecules (CORMs) represent a
      pharmacological alternative to CO gas inhalation. Here, we questioned whether
      CORM-3, a well-characterized water-soluble CORM, could prevent and reverse
      pulmonary hypertension (PH) in chronically hypoxic mice and in smooth muscle
      promoter 22 serotonin transporter mice overexpressing the serotonin transporter
      in smooth muscle cells (SMCs). APPROACH AND RESULTS: Treatment with CORM-3 (50
      mg/kg per day once daily) for 3 weeks prevented PH, right ventricular
      hypertrophy, and distal pulmonary artery muscularization in mice exposed to
      chronic hypoxia and partially reversed PH in smooth muscle promoter 22 serotonin
      transporter mice by reducing Ki67 dividing pulmonary artery SMCs (PA-SMCs). In
      these models, CORM-3 markedly increased lung p21 mRNA and protein levels and p21
      stained PA-SMCs. These effects contrasted with the transient pulmonary
      vasodilatation and rise in lung cGMP levels induced by a single injection of CORM
      3 in mice exposed to acute hypoxia. Studies in cultured rat PA-SMCs revealed that
      the inhibitory effects of CORM-3 on cell growth were independent of cGMP
      formation but associated with increased p21 mRNA and protein levels. Protection
      against PH by CORM-3 required increased lung expression of p21, as indicated by
      the inability of CORM-3 to prevent chronic hypoxia-induced PH in p21-deficient
      mice and to alter the growth of PA-SMCs derived from p21-deficient mice. CORM-3
      induced p21 overexpression was linked to p53 activation as assessed by the
      inability of CORM-3 to prevent PH and induce p21 expression in p53-deficient mice
      and in PA-SMCs derived from p53-deficient mice. CONCLUSIONS: CORM-3 inhibits
      pulmonary vascular remodeling via p21, which may represent a useful approach for
      treating PH.

PMID- 24334872
TI  - Evaluation of links between high-density lipoprotein genetics, functionality, and
      aortic valve stenosis risk in humans.
AB  - OBJECTIVE: Studies have shown that high-density lipoprotein (HDL)-raising
      compounds induce regression of aortic valve stenosis (AVS) in animal models.
      However, whether patients with AVS have an impaired HDL metabolism is unknown.
      APPROACH AND RESULTS: A total of 1435 single nucleotide polymorphisms in genes
      associated with HDL cholesterol levels (in or around GALNT2, LPL, ABCA1, APOA5,
      SCARB1, LIPC, CETP, LCAT, LIPG, APOC4, and PLTP) were genotyped in 382 patients
      with echocardiography-confirmed AVS (aortic jet velocity >=2.5 m/s) and 401
      controls. After control for multiple testing, none of the genetic variants showed
      a positive association with case/control status (adjusted P>=0.05 for all single
      nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol
      levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity,
      pre-beta-HDL, HDL size, and 4 parameters of cholesterol efflux capacity were
      measured in apolipoprotein B-depleted serum samples from 86 patients with and 86
      patients without AVS. Cholesterol efflux capacity was measured using J774
      macrophages with and without stimulation of ATP-binding cassette A-1 expression
      by cAMP, and HepG2 hepatocytes for scavenger receptor class B type 1-mediated
      efflux. None of these parameters were different between cases and controls.
      However, compared with patients without coronary artery disease, sera from
      patients with coronary artery disease had lower HDL cholesterol levels, scavenger
      receptor class B type 1-mediated efflux, and HDL size (P<=0.003), independently
      of the presence or absence of AVS. CONCLUSIONS: Results of the present study
      suggest that, based on HDL genetics and HDL functionality, HDL metabolism does
      not seem to predict the risk of AVS. Because of our limited sample size,
      additional studies are needed to confirm these findings.

PMID- 24334873
TI  - Apolipoprotein A-I protection against atherosclerosis is dependent on genetic
      background.
AB  - OBJECTIVE: Inbred mouse strains have different susceptibilities to experimental
      atherosclerosis. The C57BL/6 strain is among the most sensitive and has,
      therefore, been the most widely used in atherosclerosis studies, whereas many
      strains are resistant. The FVB/N strain is highly resistant to atherosclerosis on
      the apolipoprotein E (apoE)- and low-density lipoprotein (LDL) receptor-deficient
      backgrounds. High-density lipoprotein and its major apoprotein, apoA-I, have been
      shown to be protective against atherogenesis on the C57BL/6 background. We here
      examine the influence of genetic background on the atheroprotective nature of
      apoA-I. APPROACH AND RESULTS: ApoE-deficient/apoA-I-deficient mice were generated
      in the C57BL/6 and FVB/N strains from apoE-deficient mice. After 6 to 10 weeks on
      a Western-type diet, plasma lipids and atherosclerotic lesion size were assessed.
      Macrophage recruitment, cholesterol regulation, and blood monocyte levels were
      examined as potential mechanisms driving lesion size differences. FVB/N knockout
      mice had higher plasma very-LDL/LDL cholesterol than their C57BL/6 counterparts.
      ApoA-I deficiency decreased very-LDL/LDL cholesterol in C57BL/6 mice but not in
      FVB/N mice. FVB/N single and double knockout mice had less lesion than C57BL/6 6
      to 10 weeks on diet. ApoA-I deficiency augmented lesion development only in
      C57BL/6 mice. Macrophage recruitment to thioglycollate-treated peritoneum and
      diet-induced blood monocyte levels reflected the pattern of lesion development
      among the 4 genotypes. ApoA-I deficiency increased macrophage cholesterol content
      only in C57BL/6. FVB/N plasma was a better acceptor for macrophage cholesterol
      efflux than C57BL/6. CONCLUSIONS: ApoA-I is atheroprotective only in certain
      genetic contexts. In the C57BL/6 context, but not FVB/N, apoA-I decreases
      inflammatory macrophage recruitment and monocytosis, contributors to lesion
      formation.

PMID- 24334874
TI  - Prospective urodynamic model for prediction of urinary incontinence after robot
      assisted radical prostatectomy.
AB  - OBJECTIVES: To assess the preoperative urodynamic predictors of urinary
      incontinence (UI) 1 year after robot-assisted radical prostatectomy (RARP) and to
      design a nomogram capable of predicting its occurrence. MATERIALS AND METHODS:
      Our prospective study included 58 previously continent patients who underwent
      RARP, in most cases, bilateral nerve-sparing and bladder neck preservation. A
      urodynamic examination including a urethral pressure profile was performed
      preoperatively. Multivariate analysis was used to assess the predictors for the
      need to use 1 or more pads/day and a nomogram was constructed. RESULTS: There was
      a 20.6% incidence of UI at 1 year after RARP. Bladder compliance, maximum
      urethral closure pressure and the development of bladder outlet obstruction,
      correlated well with the incidence of UI on the multivariate analysis (p = 0.043,
      0.001, and 0.05, respectively). CONCLUSION: Bladder compliance <27.8 ml/cm H2O,
      maximum urethral closure pressure <50.3 cm H2O and the bladder outlet obstruction
      are independent urodynamic factors correlating with UI after RARP. The new
      nomogram can objectively predict a patient likelihood of requiring 1 or more
      pads/day 1 year after RARP with a good accuracy.

PMID- 24334875
TI  - Aberrant reduction of MiR-141 increased CD47/CUL3 in Hirschsprung's disease.
AB  - BACKGROUND: MiR-141 has been confirmed to be associated with various human
      diseases. However, whether miR-141 is involved in the pathogenesis of
      Hirschsprung's disease (HSCR) remains unknown. Here, we design the experiment to
      reveal the relationship between miR-141 and HSCR. METHODS: Quantitative real-time
      PCR and Western blot were used to detect the expression levels of miR-141 and its
      potential genes in 70 tissues of HSCR compared with 60 controls. Bisulfite
      sequencing PCR (BSP) assay was applied to explain the possible mechanism of the
      aberrant expression level of miR-141. We employed a dual-luciferase reporter
      assay to validate the regulation relation between miR-141 and CD47/CUL3. Cell
      migration, proliferation, apoptosis, and cell cycle progression were examined by
      transwell assay, MTT assay, and flow cytometry, respectively. RESULTS: MiR-141
      was down-regulated whereas CD47 and CUL3 expression was increased in colon
      tissues from patients with HSCR compared with control group, The increased level
      of CD47 and CUL3 induced by miR-141 reduced proliferation and migration of 293T
      and SH-SY5Y cells. Furthermore, this suppression was reversed by reducing of CD47
      and CUL3. Hypermethylation of a CpG Island in the promoter region of miR-141 gene
      was confirmed in HSCR tissues. CONCLUSION: Aberrant reduction of miR-141 may play
      an important role in the pathogenesis of HSCR with the inhibiting affection on
      cell migration and proliferation abilities. The present study demonstrates for
      the first time the role of miR-141 and its target genes in the occurrence of
      HSCR, and provides us a new direction for the study of the pathogenesis of
      Hirschsprung's disease.

PMID- 24334876
TI  - Usefulness of contrast injection during balloon aortic valvuloplasty before
      transcatheter aortic valve replacement: a pilot study.
AB  - AIMS: To describe a technique of simultaneous aortography and balloon aortic
      valvuloplasty (BAV) before transcatheter aortic valve replacement (TAVR), and to
      show how this technique affected TAVR prosthesis selection and procedural
      outcomes. METHODS AND RESULTS: One hundred and eleven patients underwent
      simultaneous contrast injection during valvuloplasty pre-TAVR to confirm the
      indication for prosthesis size provided by non-invasive imaging studies. A
      successful injection was achieved in 95 patients (85.5%). No events occurred
      during simultaneous BAV and contrast injection. In 12 (10.8%) patients the
      prosthesis size implanted was different from the recommendations provided by the
      non-invasive imaging examinations. In nine of these cases (75.0%) it was decided
      to implant a larger prosthesis than that originally suggested, in the remaining
      three cases (25.0%) a smaller valve was implanted. Device success in this
      particular subset of patients was 100%. Overall device success was 92.8%. Post
      procedural moderate paravalvular regurgitation was reported in 5.4% of patients.
      CONCLUSIONS: In patients with severe aortic valve stenosis, a technique of
      simultaneous aortography and balloon valvuloplasty as an adjunct to non-invasive
      imaging modalities for transcatheter prosthesis selection is feasible, and leads
      to a change in TAVR strategy in a modest number of patients. Larger studies are
      necessary to confirm these findings, and to assess whether this method is capable
      of enhancing the safety of the TAVR procedure.

PMID- 24334877
TI  - Detection of herpes viruses by multiplex and real-time polymerase chain reaction
      in bronchoalveolar lavage fluid of patients with acute lung injury or acute
      respiratory distress syndrome.
AB  - BACKGROUND: Human herpes viruses (HHVs) are important pathogens in acute lung
      injury (ALI) and acute respiratory distress syndrome (ARDS). Rapid and efficient
      diagnostic tools are needed to detect HHVs in the lung in ALI/ARDS patients.
      OBJECTIVES: This study aimed to evaluate the usefulness of multiplex and real
      time polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid
      (BALF) for detecting HHV reactivation in ALI/ARDS patients. METHODS: Between
      August 2008 and July 2012, eighty-seven BALF samples were obtained from ALI/ARDS
      patients with unknown etiology and analyzed for HHVs. The types of HHVs in the
      BALF samples were determined using qualitative multiplex PCR followed by
      quantitative real-time PCR. RESULTS: Multiplex PCR identified herpes simplex
      virus type 1 (HSV-1) (n = 11), Epstein-Barr virus (EBV) (n = 16), cytomegalovirus
      (CMV) (n = 21), HHV type 6 (HHV-6) (n = 2), and HHV-7 (n = 1) genomic DNA in 35
      (40%) of the BALF samples, including 14 (16%) samples containing 2 or 3 HHV
      types. CMV and EBV reactivation was rare in immunocompetent patients, whereas
      reactivation of HSV-1 was predominantly observed in intubated patients regardless
      of their immune status. Overall, HHVs were almost exclusively found in patients
      with immunosuppression or endotracheal intubation. Real-time PCR detected 0.95
      1.59 * 10(6) copies of viral DNA/MUg human genome DNA, and HSV-1 (n = 4), CMV (n
      = 9), and HHV-6 (n = 1) were identified as potentially pathogenic agents.
      CONCLUSIONS: The implementation of multiplex and real-time PCR of BALF was
      feasible in ALI/ARDS patients, which allowed efficient detection and
      quantification of HHV DNA.

PMID- 24334878
TI  - Steroid oestrogens in the environment: an Australian perspective.
AB  - Endocrine disrupting compounds (EDCs) have been in the scientific spotlight since
      the 1980s. However, there has been much less research reported in Australia than
      in other developed countries and little information is known about how these
      compounds interact with native Australian species compared to European and North
      American fauna. This is of concern because Australia has distinct wildlife and
      environments that face increasing intensity and frequency of extreme, climatic
      events compared to northern hemisphere countries. Since oestrogenic compounds
      cannot be prevented from entering wastewater their management and removal must
      occur at wastewater treatment plants. Biological treatment is the most effective
      tool in this regard; however the financial and environmental costs must be
      balanced with the environmental benefit to effectively plan treatment options.
      Since standard risk assessment models and procedures developed internationally
      are unlikely to translate well to Australian ecosystems, new, novel and localised
      research on both the monitoring and assessment of EDCs in Australian wastewater
      and receiving aquatic environments is recommended. This includes the development
      of relevant bioassays and application of treatment technologies that reflect the
      local community and climate. 

PMID- 24334879
TI  - Kinetics of aerobic oxidation of volatile sulfur compounds in wastewater and
      biofilm from sewers.
AB  - Laboratory experiments were conducted to investigate the kinetics of aerobic
      chemical and biological oxidation of selected odorous volatile sulfur compounds
      (VSCs) by wastewater and biofilm from sewers. The VSCs included methyl mercaptan
      (MeSH), ethyl mercaptan (EtSH), dimethyl sulfide (DMS) and total inorganic
      sulfide, which have all been reported as the main constituents of foul sewer gas.
      Samples of wastewater and biofilm for the experiments were obtained from two
      locations that differed significantly with respect to the occurrence of VSCs. One
      location represented an odor hot-spot downstream of a force main and the other
      was a gravity sewer transporting young aerobic wastewater. The kinetics of VSC
      oxidation for both wastewater and suspended biofilm samples followed a first
      order rate equation. The average values of the reaction rate constants
      demonstrated the following order of reactivity: total inorganic sulfide > EtSH >=
      MeSH >> DMS. Except for total inorganic sulfide oxidation in wastewater, kinetic
      parameters for each VSC were of similar magnitude for the two locations. In the
      wastewater from the odor hot-spot, sulfide inorganic oxidation rates were
      approximately 12 times faster than in the aerobic wastewater. 

PMID- 24334880
TI  - Temperature, plant species and residence time effects on nitrogen removal in
      model treatment wetlands.
AB  - Total nitrogen (TN) removal in treatment wetlands (TWs) is challenging due to
      nitrogen cycle complexity and the variation of influent nitrogen species. Plant
      species, season, temperature and hydraulic loading most likely influence root
      zone oxygenation and appurtenant nitrogen removal, especially for ammonium-rich
      wastewater. Nitrogen data were collected from two experiments utilizing batch
      loaded (3-, 6-, 9- and 20-day residence times), sub-surface TWs monitored for at
      least one year during which temperature was varied between 4 and 24  degrees C.
      Synthetic wastewater containing 17 mg/l N as NH4 and 27 mg/l amino-N, 450 mg/l
      chemical oxygen demand (COD), and 13 mg/l SO4-S was applied to four replicates of
      Carex utriculata, Schoenoplectus acutus and Typha latifolia and unplanted
      controls. Plant presence and species had a greater effect on TN removal than
      temperature or residence time. Planted columns achieved approximately twice the
      nitrogen removal of unplanted controls (40-95% versus 20-50% removal) regardless
      of season and temperature. TWs planted with Carex outperformed both Typha and
      Schoenoplectus and demonstrated less temperature dependency. TN removal with
      Carex was excellent at all temperatures and residence times; Schoenoplectus and
      Typha TN removal improved at longer residence times. Reductions in TN were not
      accompanied by increases in NO3, which was consistently below 1 mg/l N. 

PMID- 24334881
TI  - Use of seawater for the boron-doped diamond electrochemical treatment of diluted
      vinasse wastewater.
AB  - Vinasse wastewater of high organic content (COD = 131,000 mg/L) and low
      biodegradability (BOD5/COD = 0.11) cannot be easily managed and usually require
      several consecutive treatment steps. The objective of this work was to dilute
      vinasse wastewater with seawater and then subject them to electrochemical
      oxidation over boron-doped diamond (BDD) electrodes. The use of seawater is a
      rational and novel approach for plants close to the seashore since it may achieve
      the desirable levels of effluent concentration and conductivity without consuming
      other water resources and extra electrolytes. Experiments were conducted at
      initial COD values of 830-8,400 mg/L, NaCl concentrations of 34-200 mM and
      current densities of 70-200 mA/cm(2) for up to 5 hours. The effect of current
      density and NaCl concentration was marginal on the electrochemical treatment,
      while the single most important parameter was the initial COD concentration. The
      order of reaction for COD reduction appears to be 'first' at low effluent
      concentrations and it decreases to 'zero' at higher concentrations, denoting the
      importance of the ratio of organics to reactive radicals concentration. Based on
      COD and total organic carbon data, it is postulated that degradation occurs
      predominantly through total oxidation (i.e. mineralization) to carbon dioxide and
      water, which is characteristic of BDD anodes. 

PMID- 24334882
TI  - In situ growth of monodispersed Fe3O4 nanoparticles on graphene for the removal
      of heavy metals and aromatic compounds.
AB  - We report on the efficient removal of heavy metal ions and aromatic compounds
      from simulated wastewater with a nanocomposite. The nanocomposite was obtained
      via thermal decomposition of the precursor Fe(acac)3 onto the surface of
      graphene, modified by diethylenetriamine pentaacetic anhydride through dopamine.
      It was found that the maximum adsorption capacity of the nanocomposite toward
      Cu(2+) and naphthalene was 207.9 and 72.2 mg g(-1) respectively, displaying a
      high efficiency for the removal of heavy metal ions as well as aromatic compounds
      at pH 7.0 and 293 K. The Langmuir for naphthalene and the Freundlich for the
      Cu(2+) adsorption isotherms were applicable for describing the removal processes.
      Furthermore, the nanocomposite was carefully examined by transmission electron
      microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Raman
      spectra, and UV-vis spectroscopy. This work provides a very efficient, fast and
      convenient approach to exploring a promising nanocomposite for water treatment. 

PMID- 24334883
TI  - An almost-parameter-free harmony search algorithm for groundwater pollution
      source identification.
AB  - The spatiotemporal characterization of unknown sources of groundwater pollution
      is frequently encountered in environmental problems. This study adopts a
      simulation-optimization approach that combines a contaminant transport simulation
      model with a heuristic harmony search algorithm to identify unknown pollution
      sources. In the proposed methodology, an almost-parameter-free harmony search
      algorithm is developed. The performance of this methodology is evaluated on an
      illustrative groundwater pollution source identification problem, and the
      identified results indicate that the proposed almost-parameter-free harmony
      search algorithm-based optimization model can give satisfactory estimations, even
      when the irregular geometry, erroneous monitoring data, and prior information
      shortage of potential locations are considered. 

PMID- 24334884
TI  - Fe3O4 nanoparticles as an efficient heterogeneous Fenton catalyst for phenol
      removal at relatively wide pH values.
AB  - In order to promote the practical application of the heterogeneous Fenton process
      in wastewater treatment, Fe3O4 nanoparticles were prepared and used to degrade
      organic pollutants efficiently over a wide pH range, using phenol as a model.
      During fabrication, the effects of Fe(2+)/Fe(3+) ratio and thermal treatment
      temperature were investigated and optimized. Using a transmission electron
      microscope and X-ray diffraction, the nanoparticles were found in the form of
      Fe3O4 with an average size of 15 nm. The effects of Fe3O4 nanoparticle
      concentration H2O2 concentration, and pH on the removal efficiency and chemical
      oxygen demand (COD) abatement efficiency of phenol were investigated. Under
      optimized conditions, the nano-Fe3O4 heterogeneous Fenton system could achieve
      phenol and COD removal efficiencies of 100 and 70% respectively. This
      nanocatalyst was observed to have a high efficiency at a wider pH range (2-9),
      and a possible mechanisms for this effect was proposed. 

PMID- 24334885
TI  - Combination of microalgae cultivation with membrane processes for the treatment
      of municipal wastewater.
AB  - The treatment of wastewater by microalgae cultivation has attracted more and more
      attention. However, the way to harvest microalgae cells from the wastewater and
      the treatment of the large quantity of residual solution have become critical
      issues. In this work, a new approach for the treatment of municipal wastewater is
      presented. The combination of flocculation for removing mainly microalgae and
      thereafter membrane filtration for chemical oxygen demand (COD) and conductivity
      reduction of the residual solution after flocculation is discussed. The COD
      concentration of the wastewater decreased from 260 to 84 mg/L after flocculation
      by chitosan. Five ultrafiltration (UF) membranes and two nanofiltration (NF)
      membranes were used for filtration to find a suitable membrane for COD and
      conductivity reduction. Among the five UF membranes, GR82PE showed the best
      performance, whose permeate flux and COD retention at 4 bar were 189.66
      L/(m(2).h) and 43.03%, respectively. NF membranes showed higher COD and
      conductivity retentions than UF membranes. The COD retention of Desal5-DK reached
      98.3% at 20 bar. Lastly, the flux recovery after the filtration test of each
      membrane is also discussed. 

PMID- 24334886
TI  - Modeling low impact development potential with hydrological response units.
AB  - Evaluations of benefits of implementing low impact development (LID) stormwater
      management techniques can extend up to a watershed scale. This presents a
      challenge for representing them in watershed models, since they are typically
      orders of magnitude smaller in size. This paper presents an approach that is
      focused on trying to evaluate the benefits of implementing LIDs on a lot level.
      The methodology uses the concept of urban hydrological response Unit and results
      in developing and applying performance curves that are a function of lot
      properties to estimate the potential benefit of large-scale LID implementation.
      Lot properties are determined using a municipal geographic information system
      database and processed to determine groups of lots with similar properties. A
      representative lot from each group is modeled over a typical rainfall year using
      USEPA Stormwater Management Model to develop performance functions that relate
      the lot properties and the change in annual runoff volume and corresponding
      phosphorus loading with different LIDs implemented. The results of applying
      performance functions on all urban areas provide the potential locations, benefit
      and cost of implementation of all LID techniques, guiding future decisions for
      LID implementation by watershed area municipalities. 

PMID- 24334887
TI  - The effect of direct addition of iron(III) on anaerobic digestion efficiency and
      odor causing compounds.
AB  - The role of iron addition to sewage sludge prior to anaerobic digestion was
      evaluated to determine the effect of iron on digestion performance and generation
      of odor-causing compounds. Hydrogen sulfide (H2S) and volatile organic sulfur
      compounds (VOSCs) were the odorous gases evaluated in this study. Samples were
      obtained from seven municipal wastewater treatment plants (WWTPs), and batch
      anaerobic digestion tests were conducted using primary and secondary sludges at
      30 day solids retention time (SRT) under mesophilic conditions. Volatile solid
      removal (VSR) was highly predictable with background iron concentrations measured
      in the combined sludge. They were likely to increase as influent iron content
      increased. 1.25% w/w ferric chloride (FeCl3) was added to the anaerobic digester
      feed in order to simulate iron addition for sulfide control in full-scale WWTPs.
      The results showed that it had a positive impact on digestion performance with
      higher VSR and odor control with reduced H2S and TVOSCs in the headspace gas of
      dewatered biosolids considered in the tests. Ferric chloride is considered a
      beneficial additive as a strategy for an odor mitigation, not to mention more
      efficient digestion under anaerobic conditions. 

PMID- 24334888
TI  - Hydraulics characteristics of tipping sediment flushing gate.
AB  - This paper highlights a preliminary study on the potential of a tipping flush
      gate to be used in an open storm drain to remove sediment. The investigation was
      carried out by using a plasboard model of the tipping flush gate installed in a
      rectangular flume. A steady flow experiment was carried out to determine the
      discharge coefficients and also the outflow relationship of the tipping flush
      gate. The velocity produced by the gate at various distances downstream of the
      gate during flushing operation was measured using a flowmeter and the velocity at
      all the points was higher than the recommended self-cleansing design available in
      the literature. A preliminary experiment on the efficiency of flushing was
      conducted using uniform sediment with d50 sizes of 0.81, 1.53 and 4.78 mm.
      Results generally showed that the number of flushes required to totally remove
      the sediment from the initial position by a distance of 1 m increased by an
      average of 1.50 times as the sediment deposit bed thickness doubled. An equation
      relating the number of flushes required to totally remove the sediment bed for 1
      m with the sediment bed deposit thickness was also developed for the current
      study. 

PMID- 24334889
TI  - Analyzing the spatial and temporal characteristics of membrane fouling.
AB  - Fouling characteristics of crossflow flat-sheet membranes for two Nanofiltration
      (NF), one Ultrafiltration (UF), and one Microfiltration (MF) membranes were
      analyzed using 12.5 parts per million (mg/L) FeCl3 solution and 350 mg/L copper
      nanofluid. FeCl3 solution represents dissolved contaminant whereas copper
      nanofluid simulates particulate contaminant. The spatial and temporal fouling
      evolutions were captured using digital photography and analyzed using ImageJ
      software. FeCl3 fouling studies for one NF membrane showed uniform fouling
      whereas for the other NF membrane, isolated fouling was apparent and the fouling
      initiated at the outlet then gradually extended towards the inlet. Copper
      nanoparticle fouling studies analyzed through gravimetric and image processing
      revealed spatial and temporal fouling developments. Both non-equilibrium and
      equilibrium fouling stages/regions were evaluated through fouling density
      analysis. 

PMID- 24334890
TI  - Distribution of polycyclic aromatic hydrocarbons in coke plant wastewater.
AB  - The subject of examinations presented in this paper is the distribution of
      polycyclic aromatic hydrocarbons (PAHs) between solid and liquid phases in
      samples of raw wastewater and wastewater after treatment. The content of 16 PAHs
      according to the US EPA was determined in the samples of coke plant wastewater
      from the Zdzieszowice Coke Plant, Poland. The samples contained raw wastewater,
      wastewater after physico-chemical treatment as well as after biological
      treatment. The SigmaPHA16 content varied between 255.050 MUg L(-1) and 311.907
      MUg L(-1) in raw wastewater and between 0.940 and 4.465 MUg L(-1) in wastewater
      after full treatment. Investigation of the distribution of PAHs showed that 71
      84% of these compounds is adsorbed on the surface of suspended solids and 16-29%
      is dissolved in water. Distribution of individual PAHs and SigmaPHA16 between
      solid phase and liquid phase was described with the use of statistically
      significant, linear equations. The calculated values of the partitioning
      coefficient Kp changed from 0.99 to 7.90 for naphthalene in samples containing
      mineral-organic suspension and acenaphthylene in samples with biological
      activated sludge, respectively. 

PMID- 24334891
TI  - Reverse osmosis concentrate treatment by chemical oxidation and moving bed
      biofilm processes.
AB  - In the present work, four oxidation techniques were investigated (O3, O3/UV,
      H2O2/O3, O3/H2O2/UV) to pre-treat reverse osmosis (RO) concentrate before
      treatment in a moving-bed biofilm reactor (MBBR) system. Without previous
      oxidation, the MBBR was able to remove a small fraction of the chemical oxygen
      demand (COD) (5-20%) and dissolved organic carbon (DOC) (2-15%). When the
      concentrate was previously submitted to oxidation, DOC removal efficiencies in
      the MBBR increased to 40-55%. All the tested oxidation techniques improved
      concentrate biodegradability. The concentrate treated by the combined process
      (oxidation and MBBR) presented residual DOC and COD in the ranges of 6-12 and 25
      41 mg L(-1), respectively. Nitrification of the RO concentrate, pre-treated by
      oxidation, was observed in the MBBR. Ammonium removal was comprised between 54
      and 79%. The results indicate that the MBBR was effective for the treatment of
      the RO concentrate, previously submitted to oxidation, generating water with an
      improved quality. 

PMID- 24334892
TI  - Quantitative estimation of groundwater recharge ratio along the riparian of the
      Yellow River.
AB  - Quantitative estimation of groundwater recharge is crucial for limited water
      resources management. A combination of isotopic and chemical indicators has been
      used to evaluate the relationship between surface water, groundwater, and
      rainfall around the riparian of the Yellow River in the North China Plain (NCP).
      The ion molar ratio of sodium to chloride in surface- and groundwater is 0.6 and
      0.9, respectively, indicating cation exchange of Ca(2+) and/or Mg(2+) for Na(+)
      in groundwater. The deltaD and delta(18)O values in rainfall varied from -64.4 to
      -33.40/00 and from -8.39 to -4.490/00. The groundwater samples have deltaD values
      in the range of -68.7 to -58.00/00 and delta(18)O from -9.29 to -6.850/00. The
      delta(18)O and deltaD in surface water varied from -8.51 to -7.230/00 and from 
      64.42 to -53.730/00. The average values of both deltaD and delta(18)O from
      surface water are 3.920/00 and 0.570/00, respectively, higher compared to
      groundwater. Isotopic composition indicated that the groundwater in the riparian
      area of the Yellow River was influenced by heavy rainfall events and seepage of
      surface water. The mass balance was applied for the first time to estimate the
      amount of recharge, which is probably 6% and 94% of the rainfall and surface
      water, respectively. 

PMID- 24334893
TI  - Influence of process parameters on phosphorus recovery by struvite formation from
      urine.
AB  - Batch experiments were conducted to examine the influence of various process
      parameters on phosphorus (P) recovery by struvite formation from urine. The
      results showed that the Mg/P molar ratio is one of the most important parameters
      affecting P recovery. The Mg/P molar ratio of 1.3 was found the most reasonable
      for struvite formation, and the P removal efficiency reached more than 96.6%. An
      increase in pH of urine solutions from 8.7 to 10.0 did not significantly affect P
      removal, but the quality of crystal formed at pH 10.0 was poor based on scanning
      electron microscopy analysis. A longer mixing time positively affected struvite
      formation, and compared to without mixing, the P removal efficiency increased
      from 72.7 to 97.3% after 5 min of mixing. The addition of seed material had no
      influence on the P removal efficiency, but contributed to the formation of
      struvite clusters. 

PMID- 24334894
TI  - Degradation of Orange II in aqueous solution by a novel electro/Fe3O4 process.
AB  - The removal of Orange II in aqueous solution by Fe3O4 enhanced anode oxidation
      (EC/Fe3O4 process) was performed in an electrochemical reactor. The process
      involved the use of a dimensionally stable anode and a stainless steel cathode.
      Fe3O4 was performed as particle electrodes to increase mass transfer coefficient
      and reduce energy consumption. Various parameters were investigated to optimize
      the process, including initial pH, Fe3O4 dosage and current density. The results
      indicated that the decolorization of Orange II followed pseudo first-order
      kinetics. The decolorization was favorable in acidic media than in neutral or
      alkaline solution, while it increased with the Fe3O4 dosage and current density.
      The total organic carbon (TOC) removal efficiency was 33.2% after 120 min
      reaction. The X-ray photoelectron spectroscopy was applied to investigate the
      surface properties of Fe3O4 before and after reaction. 

PMID- 24334895
TI  - Analysing urban resilience through alternative stormwater management options:
      application of the conceptual Spatial Decision Support System model at the
      neighbourhood scale.
AB  - Recent changes in cities and their environments, caused by rapid urbanisation and
      climate change, have increased both flood probability and the severity of
      flooding. Consequently, there is a need for all cities to adapt to climate and
      socio-economic changes by developing new strategies for flood risk management.
      Following a risk paradigm shift from traditional to more integrated approaches,
      and considering the uncertainties of future urban development, one of the main
      emerging tasks for city managers becomes the development of resilient cities.
      However, the meaning of the resilience concept and its operability is still not
      clear. The goal of this research is to study how urban engineering and design
      disciplines can improve resilience to floods in urban neighbourhoods. This paper
      presents the conceptual Spatial Decision Support System (DS3) model which we
      consider a relevant tool to analyse and then implement resilience into
      neighbourhood design. Using this model, we analyse and discuss alternative
      stormwater management options at the neighbourhood scale in two specific areas:
      Rotterdam and New Orleans. The results obtained demonstrate that the DS3 model
      confirmed in its framework analysis that stormwater management systems can
      positively contribute to the improved flood resilience of a neighbourhood. 

PMID- 24334896
TI  - Large-scale hydropower system optimization using dynamic programming and object
      oriented programming: the case of the Northeast China Power Grid.
AB  - This paper examines long-term optimal operation using dynamic programming for a
      large hydropower system of 10 reservoirs in Northeast China. Besides considering
      flow and hydraulic head, the optimization explicitly includes time-varying
      electricity market prices to maximize benefit. Two techniques are used to reduce
      the 'curse of dimensionality' of dynamic programming with many reservoirs.
      Discrete differential dynamic programming (DDDP) reduces the search space and
      computer memory needed. Object-oriented programming (OOP) and the ability to
      dynamically allocate and release memory with the C++ language greatly reduces the
      cumulative effect of computer memory for solving multi-dimensional dynamic
      programming models. The case study shows that the model can reduce the 'curse of
      dimensionality' and achieve satisfactory results. 

PMID- 24334897
TI  - Quantification of Helicobacter pylori in the viable but nonculturable state by
      quantitative PCR in water disinfected with ozone.
AB  - Helicobacter pylori is a Gram-negative spiral-shaped bacterium that colonizes the
      gastric mucosa and is associated with gastric diseases. It may present a
      morphological adaptation when it is out of its natural environment, such as in
      water. The morphological adaptation is a coccoid form, which is a viable but non
      culturable state (VNC) in which the DNA remains active and therefore infective.
      Due to the impossibility of culture by traditional methods in the VNC state, we
      developed a methodology that includes a molecular technique, quantitative
      polymerase chain reaction (qPCR), which is capable of measuring the bacteria in
      both forms (helical and coccoidal) and therefore is able to measure a
      disinfection process and to estimate the resistance of the bacteria to ozone. The
      methodology developed measures the efficiency of the ozone disinfection when
      bacteria are in a VNC state only. Bacterial culture at 9 * 10(8)CFU/mL diluted in
      40 mL reaction volumes were exposed to a wide range of CT values (0.11-15 mg
      min/L). The results show a 3.92-log reduction when treated with 15 mg min/L. Our
      results demonstrate the feasibility of using qPCR for the quantification and
      detection of H. pylori, in coccoid form, in water systems treated with an ozone
      disinfection process. 

PMID- 24334898
TI  - Adsorptive removal of trace oxytetracycline from water by acid-modified zeolite:
      influencing factors.
AB  - Because of the wide use of antibiotics in the livestock industry, trace
      tetracycline antibiotics are frequently detected in swine wastewater and water
      bodies near pig farms. Based on natural zeolite, modified zeolite was synthesized
      by treatment with nitric acid. As one kind of typical tetracyclines,
      oxytetracycline (OTC) was chosen as the target adsorbate. Removal of trace OTC by
      modified zeolite and the effects of several main water matrices on OTC adsorption
      were studied in detail. OTC removal efficiency by acid-modified zeolite was about
      90%, compared to less than 20% by natural zeolite. In general, in acidic
      conditions the removal efficiency of OTC by modified zeolite was about 90%, which
      was much higher than 20-35% in alkaline conditions. An increase in ionic strength
      from 0.01 to 1.0 M led to a decrease in adsorption efficiency from 90 to 27%. The
      presence of 10.0 mg L(-1) dissolved humic acid accelerated sorption of OTC on
      modified zeolite, while 100.0 mg L(-1) humic acid resulted in the opposite
      effect. An increase in temperature contributed to enhancing the adsorption
      efficiency. 

PMID- 24334899
TI  - The photoconversion of gamma-hexachlorocyclohexane under UV irradiation in water,
      snow and ice.
AB  - The photochemistry of organic pollutants has received increasing attention in ice
      and snow. In this work, the photoconversion of gamma-hexachlorocyclohexane (gamma
      HCH) under UV irradiation was investigated in water, snow and ice. The
      photoconversion rate, products and mechanisms were inspected, and the effect of
      inorganic ions (NO2(-), NO3(-), HCO3(-) and Fe(2+)) was discussed. The results
      showed that gamma-HCH could be photoconverted in water, snow and ice, with the
      photoconversion rate being fastest in snow, and slowest in ice. All
      photoconversion could be described by the first-order kinetics model. In water,
      snow and ice, the common photoproducts of gamma-HCH were alpha
      hexachlorocyclohexane (alpha-HCH) and pentachlorocyclohexene. alpha-HCH was
      generated by a change in the bonding of a chlorine atom in gamma-HCH;
      pentachlorocyclohexene was generated by the removal of a molecule of chlorine
      hydride from a molecule of gamma-HCH. Different concentrations of NO2(-), NO3(-)
      and HCO3(-) all inhibited the photoconversion of gamma-HCH, and the inhibition
      effect decreased with increasing concentrations of NO2(-) and NO3(-), but
      increased with the increasing concentrations of HCO3(-). Different concentrations
      of Fe(2+) promoted the photoconversion of gamma-HCH in water and ice, but had
      little effect in snow. 

PMID- 24334900
TI  - Blue and grey water footprint of textile industry in China.
AB  - Water footprint (WF) is a newly developed idea that indicates impacts of
      freshwater appropriation and wastewater discharge. The textile industry is one of
      the oldest, longest and most complicated industrial chains in the world's
      manufacturing industries. However, the textile industry is also water intensive.
      In this paper, we applied a bottom-up approach to estimate the direct blue water
      footprint (WFdir,blue) and direct grey water footprint (WFdir,grey) of China's
      textile industry at sector level based on WF methodology. The results showed that
      WFdir,blue of China's textile industry had an increasing trend from 2001 to 2010.
      The annual WFdir,blue surpassed 0.92 Gm(3)/yr (giga cubic meter a year) since
      2004 and rose to peak value of 1.09 Gm(3)/yr in 2007. The original and residuary
      WFdir,grey (both were calculated based on the concentration of chemical oxygen
      demand (CODCr)) of China's textile industry had a similar variation trend with
      that of WFdir,blue. Among the three sub-sectors of China's textile industry, the
      manufacture of textiles sector's annual WFdir,blue and WFdir,grey were much
      larger than those of the manufacture of textile wearing apparel, footware and
      caps sector and the manufacture of chemical fibers sector. The intensities of
      WFdir,blue and WF(res)dir,grey of China's textile industry were year by year
      decreasing through the efforts of issuing restriction policies on freshwater use
      and wastewater generation and discharge, and popularization of water saving and
      wastewater treatment technologies.

PMID- 24334901
TI  - Suitability of ozone pre-treatment for amoxicillin wastewater.
AB  - This study deals with the ozonation of amoxicillin in real pharmaceutical
      wastewater and its efficacy as a pre-treatment, prior to biological degradation
      by a mixed culture of bacteria in a sequencing batch reactor (SBR). An ozone
      utilization of 0.27 g/g-COD (chemical oxygen demand) lowered the pH of the
      wastewater to 6.6, reduced the specific ultraviolet absorption by 43% and
      increased the biochemical oxygen demand (BOD) concentration by 37%. The BOD:COD
      ratio became equal to 0.89, making the ozonated wastewater seemingly suitable for
      biological treatment; however, when the ozonated effluent was fed to the SBR, the
      reactor performance degraded, an effect which was attributed to ozonation by
      products. In conclusion, ozonation might not be a suitable pre-treatment for
      pharmaceutical wastewater containing amoxicillin, and biotreatment with properly
      acclimated biomass may be a better option for treatment of such pharmaceutical
      wastewater. 

PMID- 24334902
TI  - Copper(II) removal from aqueous solutions by adsorption on non-treated and
      chemically modified cactus fibres.
AB  - The adsorption efficiency of a biomass by-product (cactus fibres) regarding the
      removal of copper(II) from aqueous solutions has been investigated before and
      after its chemical treatment. The chemical treatment of the biomass by-product
      included phosphorylation and MnO2-coating. The separation/removal efficiency has
      been studied as a function of pH, Cu(II) concentration, ionic strength,
      temperature and contact time. Evaluation of the experimental data shows that the
      MnO2-coated product presents the highest adsorption capacity, followed by the non
      treated and phosphorylated material. Regarding the effect of ionic
      strength/salinity on the adsorption, in contrast to the removal efficiency of the
      phosphorylated product, which is significantly affected, the MnO2-coated and non
      treated material don't show any effect, indicating the formation of inner-sphere
      surface complexes. The adsorption reaction is in all cases endothermic and
      relatively fast, particularly the adsorption on the MnO2-coated product. The
      results of the present study indicate that for the removal of bivalent metal-ions
      from contaminated waters the MnO2-coated material is expected to be the most
      effective adsorbent and an alternative to MnO2 resins for the treatment of
      environmentally relevant waters. 

PMID- 24334903
TI  - Lipid profile characterization of wastewaters from different origins.
AB  - Lipids in wastewaters are potential raw material for renewable diesel, but may
      complicate biological treatment of wastewaters. The lipid composition of palm oil
      mill effluent (POME), chemithermomechanical pulp mill (CTMP) wastewater and
      municipal wastewater (MWW) was studied with a combination of thin-layer
      chromatography and nuclear magnetic resonance. Gravimetrically determined content
      of extracted lipids from the solids of POME and CTMP wastewater were 8.4 +/- 1.2
      g/L (19.6 +/- 0.8% of dry weight) and 0.17-0.23 g/L (12.4-18.5%), respectively,
      while MWW contained 0.021 +/- 0.002 g/L (9.3 +/- 1.4%) of lipids. All lipid
      extracts contained mono-, di- and triacylglycerols (TAGs) and free fatty acids
      (FFAs). In POME, lipids were mostly TAGs (11.5 +/- 0.2 MUmol/10 mg of lipid
      extract). In CTMP and MWW lipid composition was more diverse than in POME
      containing also sterol derivatives and fatty acid methyl esters and the main
      lipids were FFAs. 

PMID- 24334904
TI  - Decolorization of Crystal Violet by ultrasound/heterogeneous Fenton process.
AB  - Activated-carbon-supported iron oxides were prepared and used as a catalyst in an
      integrated ultrasound/heterogeneous Fenton process for the decolorization of
      Crystal Violet. A synergistic effect was observed when ultrasound was combined
      with the heterogeneous Fenton process. The decolorization efficiency increased
      with the increasing power density and catalyst dosage, but decreased with the
      increase of initial pH value. There exists an optimal hydrogen peroxide
      concentration for decolorization. Catalyst stability was evaluated by measuring
      iron leaching in solution. The decolorization efficiency was 88% under the
      optimal conditions. Toxicity test with Daphnia magna showed that the acute
      toxicity of dye solution decreased significantly after the treatment by the
      heterogeneous sono-Fenton process. 

PMID- 24334905
TI  - Macrophage migration inhibitory factor deficiency augments doxorubicin-induced
      cardiomyopathy.
AB  - BACKGROUND: Recent evidence has depicted a role of macrophage migration
      inhibitory factor (MIF) in cardiac homeostasis under pathological conditions.
      This study was designed to evaluate the role of MIF in doxorubicin-induced
      cardiomyopathy and the underlying mechanism involved with a focus on autophagy.
      METHODS AND RESULTS: Wild-type (WT) and MIF knockout (MIF(-/-)) mice were given
      saline or doxorubicin (20 mg/kg cumulative, i.p.). A cohort of WT and MIF(-/-)
      mice was given rapamycin (6 mg/kg, i.p.) with or without bafilomycin A1 (BafA1, 3
      MUmol/kg per day, i.p.) for 1 week prior to doxorubicin challenge. To consolidate
      a role for MIF in the maintenance of cardiac homeostasis following doxorubicin
      challenge, recombinant mouse MIF (rmMIF) was given to MIF(-/-) mice challenged
      with or without doxorubicin. Echocardiographic, cardiomyocyte function, and
      intracellular Ca(2+) handling were evaluated. Autophagy and apoptosis were
      examined. Mitochondrial morphology and function were examined using transmission
      electron microscopy, JC-1 staining, MitoSOX Red fluorescence, and mitochondrial
      respiration complex assay. DHE staining was used to evaluate reactive oxygen
      species (ROS) generation. MIF knockout exacerbated doxorubicin-induced mortality
      and cardiomyopathy (compromised fractional shortening, cardiomyocyte and
      mitochondrial function, apoptosis, and ROS generation). These detrimental effects
      of doxorubicin were accompanied by defective autophagolysosome formation, the
      effect of which was exacerbated by MIF knockout. Rapamycin pretreatment rescued
      doxorubicin-induced cardiomyopathy in WT and MIF(-/-) mice. Blocking
      autophagolysosome formation using BafA1 negated the cardioprotective effect of
      rapamycin and rmMIF. CONCLUSIONS: Our data suggest that MIF serves as an
      indispensable cardioprotective factor against doxorubicin-induced cardiomyopathy
      with an underlying mechanism through facilitating autophagolysosome formation.

PMID- 24334907
TI  - Macular lymphocytic arteritis: three cases questioning its classification as
      primary lymphocytic vasculitis.
AB  - BACKGROUND: Macular arteritis, macular lymphocytic arteritis (MLA) or lymphocytic
      thrombophilic arteritis all correspond to an identical new clinicopathological
      entity. Its individualization as a primary cutaneous lymphocytic arteritis is
      still controversial for certain authors as it could represent a latent form of
      cutaneous polyarteritis nodosa. MATERIALS AND METHODS: We report here 3
      additional cases of MLA, present a review of the literature and discuss the
      disease's nosology. RESULTS: MLA is characterized clinically by a benign skin
      eruption consisting in bilateral asymptomatic erythematous/hyperpigmented macules
      mainly located on the lower legs and histologically by a medium-sized cutaneous
      lymphocytic prominent arteritis present in early cutaneous lesions. CONCLUSION:
      These findings support that MLA may be considered as a chronic and indolent
      primary lymphocytic cutaneous arteritis. Nevertheless, in some cases the
      objective obliteration of cutaneous vessels underlines the need for continuous
      monitoring in MLA patients.

PMID- 24334906
TI  - Rad GTPase deletion increases L-type calcium channel current leading to increased
      cardiac contraction.
AB  - BACKGROUND: The small GTPase Rad is a negative regulator of voltage-dependent L
      type calcium channel current (ICaL); however, the effects of Rad ablation on
      cardiomyocyte function are unknown. The objective of this study is to test the
      hypothesis that Rad-depletion causes positive inotropic effects without inducing
      cardiac hypertrophy. METHODS AND RESULTS: Ventricular myocytes from adult Rad(-/
      ) mice were isolated and evaluated by patch-clamp recordings for I(Ca,L) and
      action potentials, Ca(2+) transients, and sarcomere shortening. Maximum I(CaL) is
      elevated in Rad(-/-) (maximal conductance 0.35 +/- 0.04 picoSiemens/picoFarad
      (pS/pF) wild-type; 0.61 +/- 0.14 pS/pF Rad(-/-)), decay kinetics are faster, and
      I(Ca,L) activates at lower voltages (activation midpoint -7.2 +/- 0.6 wild-type; 
      11.7 +/- 0.9 Rad(-/-)) mimicking effects of beta-adrenergic receptor stimulation.
      Diastolic and twitch calcium are elevated in Rad(-/-) (F340/380: 1.03 diastolic
      and 0.35 twitch for wild-type; 1.47 diastolic and 0.736 twitch for Rad(-/-)) and
      sarcomere shortening is enhanced (4.31% wild-type; 14.13% Rad(-/-)) at lower
      pacing frequencies. Consequentially, frequency-dependence of Ca(2+) transients is
      less in Rad(-/-), and the frequency dependence of relaxation is also blunted. In
      isolated working hearts, similar results were obtained; chiefly, +dP/dt was
      elevated at baseline and developed pressure was relatively nonresponsive to acute
      beta-adrenergic receptor stimulation. In single cells, at subphysiological
      frequencies, nonstimulated calmodulin-dependent protein kinase-sensitive calcium
      release is observed. Remarkably, Rad(-/-) hearts did not show hypertrophic growth
      despite elevated levels of diastolic calcium. CONCLUSIONS: This study
      demonstrates that the depletion of Rad GTPase is equivalent to sympathomimetic
      beta-adrenergic receptor, without stimulating cardiac hypertrophy. Thus,
      targeting Rad GTPase is a novel potential therapeutic target for Ca(2+)
      homeostasis-driven positive inotropic support of the heart.

PMID- 24334908
TI  - Urinary phytoestrogen levels and frailty in older American women of the National
      Health and Nutrition Examination Survey (NHANES) 1999-2002: a cross-sectional
      study.
AB  - BACKGROUND/AIMS: A deficit of various hormones during the process of aging and/or
      a heightened inflammatory state may be causally linked to the development of
      frailty. Phytoestrogens as weak estrogens, antioxidants, and anti-inflammatory
      agents may counteract this process. METHODS: In a cross-sectional study including
      two cycles of the National Health and Nutrition Examination Survey (NHANES, i.e.
      1999-2002), logistic regression was used to analyze the association between
      urinary concentrations of isoflavones and lignans and frailty in 600 females aged
      50 years or older (median age 66.5 years). Participants were classified as
      'frail' (meeting 3 or more of the 5 frailty criteria), 'prefrail' (meeting 1 or 2
      of the criteria), or 'robust' (meeting none of the criteria). Four percent were
      frail. RESULTS: For all of the phytoestrogens considered, the unadjusted OR were
      lower than 1 but generally not statistically significant aside from the
      association with O-desmethylangolensin (O-DMA) (OR = 0.76; 95% CI 0.61-0.92).
      Multivariate analysis did not attenuate this finding (OR = 0.74; 95% CI 0.61
      0.90). CONCLUSIONS: This first analysis of the relationship between
      phytoestrogens and frailty revealed an inverse association between urinary O-DMA
      levels and frailty in women. However, the number of frail women was low. Although
      this finding may be confounded or biased, it seems worthwhile to intensify
      research on the potential preventive effects of O-DMA.

PMID- 24334909
TI  - Persistent fever in a young woman.

PMID- 24334911
TI  - The effect of illicit financial flows on time to reach the fourth Millennium
      Development Goal in Sub-Saharan Africa: a quantitative analysis.
AB  - OBJECTIVES: This paper sets out to estimate the cost of illicit financial flows
      (IFF) in terms of the amount of time it could take to reach the fourth Millennium
      Development Goal (MDG) in 34 African countries. DESIGN: We have calculated the
      percentage increase in gross domestic product (GDP) if IFFs were curtailed using
      IFF/GDP ratios. We applied the income (GDP) elasticity of child mortality to the
      increase in GDP to estimate the reduction in time to reach the fourth MDG in 34
      African countries. PARTICIPANTS: children aged under five years. SETTINGS: 34
      countries in SSA. MAIN OUTCOME MEASURES: Reduction in time to reach the first
      indicator of the fourth MDG, under-five mortality rate in the absence of IFF.
      RESULTS: We found that in the 34 SSA countries, six countries will achieve their
      fourth MDG target at the current rates of decline. In the absence of IFF, 16
      countries would reach their fourth MDG target by 2015 and there would be large
      reductions for all other countries. CONCLUSIONS: This drain on development is
      facilitated by financial secrecy in other jurisdictions. Rich and poor countries
      alike must stem the haemorrhage of IFF by taking decisive steps towards improving
      financial transparency.

PMID- 24334910
TI  - Management of colorectal cancer and diabetes.
AB  - Colorectal cancer is associated with diabetes mellitus and both of these common
      conditions are often managed together by a surgeon. The surgical focus is usually
      upon cancer treatment rather than diabetes management. The relationship between
      colorectal cancer and diabetes is a complex one and can raise problems in both
      diagnosis and the management of patients with both conditions. This literature
      review explores the relationship between diabetes, diabetic treatment and
      colorectal cancer and addresses the issues that arise in diagnosing and treating
      this patient group. By highlighting these difficulties, this review aims to
      improve understanding and to provide clearer insight into both surgical and non
      surgical management. 

PMID- 24334912
TI  - Formative Care: Defining the purpose and clinical practice of care for the frail.

PMID- 24334913
TI  - Endovascular stent graft repair of suture-line pseudoaneurysm following ascending
      aorta replacement.
AB  - Ascending aorta pseudoaneurysm (AAPA) is an uncommon complication following
      replacement of the ascending aorta with a prosthetic graft, carry a high risk of
      rupture, and warrant urgent intervention. The open surgical procedure "gold
      standard" of care is not always favorable, as the reoperations are technically
      more difficult or patient's general condition doesn't allow proceeding. Case
      discussed is an 80-year-old male patient who presented with worsening cough and
      hemoptysis. He underwent ascending aorta replacement 10 years ago. Computed
      tomography (CT) scan revealed a contrast-filled mediastinal mass communicating
      with the ascending aorta and extended into the right lung. Due to the patient's
      advanced age, friability and clinical condition, combined with the position of
      the AAPA behind the sternum, surgery was deemed to be high risk. However,
      favorable anatomical conditions provided a safe landing zone for an endovascular
      stent. The patient underwent closed procedure. Postprocedure CT showed complete
      obliteration of the AAPA. 

PMID- 24334914
TI  - McCleery syndrome: etiology and outcome.
AB  - OBJECTIVES: Patients presenting with swelling of the upper extremity without
      thrombosis have McCleery syndrome or intermittent compression of the subclavian
      vein. The purpose of this study was to determine outcomes in these patients who
      underwent first rib resection and scalenectomy (FRRS). METHODS: Using a
      prospectively maintained database from 2003 to 2011, patients were
      retrospectively reviewed for presentation, diagnosis, treatment, and clinical
      outcomes. RESULTS: Of the patients presenting with venous thoracic outlet
      syndrome, 19 (11%; 13 F/6 M; mean age 26 [10-44]) presented with intermittent arm
      swelling, of which 3 were identified as having chronic thrombus. A total of 20
      FRRS operations were performed. CONCLUSIONS: First rib resection and scalenectomy
      is effective in relieving symptoms in patients with McCleery syndrome. These
      patients do not generally need a postoperative venogram unless they experience
      continuing symptoms. In patients with chronic thrombus, routine postoperative
      venography at 2 weeks is indicated. Patients can present with intermittent
      compression if an acute episode of deep vein thrombosis is not aggressively
      treated.

PMID- 24334915
TI  - Susceptibility-weighted imaging in the diagnosis of isolated cortical vein
      thrombosis.

PMID- 24334916
TI  - The role of the macrophage in the development of aortic dissection.

PMID- 24334918
TI  - Surface area of early visual cortex predicts individual speed of traveling waves
      during binocular rivalry.
AB  - Binocular rivalry ensues when different images are presented to the 2 eyes with
      conscious perception alternating between the possible interpretations. For large
      rivalry displays, perceptual transitions are initiated at one location and spread
      to other parts of the visual field, a phenomenon termed "traveling wave."
      Previous studies investigated the underlying neural mechanisms of the traveling
      wave and surmised that primary visual cortex might play an important role. We
      used magnetic resonance imaging and behavioral measures in humans to explore how
      interindividual differences in observers' subjective experience of the wave are
      related to anatomical characteristics of cortical regions. We measured wave speed
      in participants and confirmed the long-term stability of the individual values.
      Retinotopic mapping was employed to delineate borders of visual areas V1-V3 in
      order to determine surface area and cortical thickness in those regions. Only the
      surface areas of V1 and V2, but not V3 showed a correlation with wave speed. For
      individuals with larger V1/V2 area, the traveling wave needed longer to spread
      across the same distance in visual space. Our results highlight the role of early
      visual areas in mediating binocular rivalry and suggest possible mechanisms for
      the correlation between surface area and the traveling waves.

PMID- 24334917
TI  - Development of sensory gamma oscillations and cross-frequency coupling from
      childhood to early adulthood.
AB  - Given the importance of gamma oscillations in normal and disturbed cognition,
      there has been growing interest in their developmental trajectory. In the current
      study, age-related changes in sensory cortical gamma were studied using the
      auditory steady-state response (ASSR), indexing cortical activity entrained to a
      periodic auditory stimulus. A large sample (n = 188) aged 8-22 years had
      electroencephalography recording of ASSR during 20-, 30-, and 40-Hz click trains,
      analyzed for evoked amplitude, phase-locking factor (PLF) and cross-frequency
      coupling (CFC) with lower frequency oscillations. Both 40-Hz evoked power and PLF
      increased monotonically from 8 through 16 years, and subsequently decreased
      toward ages 20-22 years. CFC followed a similar pattern, with strongest age
      related modulation of 40-Hz amplitude by the phase of delta oscillations. In
      contrast, the evoked power, PLF and CFC for the 20- and 30-Hz stimulation were
      distinct from the 40-Hz condition, with flat or decreasing profiles from
      childhood to early adulthood. The inverted U-shaped developmental trajectory of
      gamma oscillations may be consistent with interacting maturational processes-such
      as increasing fast GABA inhibition that enhances gamma activity and synaptic
      pruning that decreases gamma activity-that may continue from childhood through to
      adulthood.

PMID- 24334919
TI  - Associations of pretreatment serum total testosterone measurements with pathology
      detected Gleason score cancer.
AB  - BACKGROUND AND OBJECTIVE: Prostate cancer is an endocrine-dependent tumor which
      is still under-investigated for physiopathology factors related to its natural
      history. The association of pretreatment total testosterone (TT) serum levels
      with prostate cancer is still a controversial topic. The objective of this study
      was to investigate potential associations and functional relationships of
      preoperative TT serum level and pathology-detected Gleason score (pGS). MATERIALS
      AND METHODS: Pretreatment and pathological variables of 220 patients operated
      with radical prostatectomy were retrospectively reviewed. Age, prostate-specific
      antigen (PSA), percentage of positive biopsy cores (P+), biopsy Gleason score
      (bGS), pGS, TT and free testosterone were the continuous variables, while
      clinical stage (cT: cT1c, cT2/3), biopsy Gleason pattern (bGP: <=3+3, 3+4, >3+4),
      pathology Gleason pattern (pGP: <=3+3, 3+4, >3+4), pathology stage (pT: pT2,
      pT3a, pT3b), pathology nodal staging (pN: pN0, pN1, pNx) and surgical margin
      invasion by cancer (R-, R+) were the categorical variables. Statistical methods
      were computed for assessing associations of TT and pGS; moreover, simple and
      multiple linear regression analysis (SLRA and MLRA) were used for assessing
      functional relationships of TT and pGS. RESULTS: High-grade tumors (pGS >=8.0)
      were associated with bGS >6.0 (p < 0.0001), pGP >=3+4 (p < 0.0001), P+ >0.31% (p
      = 0.006), cT2/3 (p = 0.01), TT >15.5 nmol/l (p = 0.0004) and, to a lesser extent,
      PSA >6.27 MUg/l (p = 0.06). The odds ratio (OR) ranked as follows: 2.01 (PSA
      >6.27 MUg/l), 2.88 (cT2/3), 3.23 (P+ >0.31%), 5.53 (TT >15.5 nmol/l) and 12.09
      (pGP >=3+4 and pGS >=8.0). On SLRA, pGS variation was significantly predicted by
      bGS (p < 0.0001), P+ (p < 0.0001), PSA (p = 0.0005) and TT (p = 0.02); on MLRA,
      pGS variation was still significantly predicted by bGS (p < 0.0001), P+ (p =
      0.04), PSA (p = 0.03) and TT (p = 0.002). When bGS, P+, PSA and TT were
      dichotomized to their median value, only bGS (p < 0.0001) and TT (p = 0.001)
      showed independence in predicting pGS variation. The best model for predicting
      pGS variations was by dichotomizing TT above its median (>15.5 nmol/l) because
      the predictive coefficient increased to 0.32, which means that patients with TT
      >15.5 have a significantly higher estimated risk for high-grade pGS than patients
      with TT <=15.5 nmol/l (OR = 1.31). CONCLUSION: In a patient population undergoing
      radical prostatectomy, increased pretreatment serum measurements of TT are
      associated with and functionally related to high-grade pGS; moreover, baseline TT
      together with bGS and PSA are important factors for predicting pGS and assessing
      high-grade tumors. Baseline TT serum levels might have prognostic potential for
      assessing treatment response for continuous as well as intermittent androgen
      deprivation therapy.

PMID- 24334920
TI  - Allergic disorders at a venerable age: a mini-review.
AB  - This review focuses on 3 allergic disorders of persons coming up against
      venerable age: asthma, allergic rhinitis, and atopic dermatitis. The prevalence
      of allergic diseases in the elderly ranges from 5 to 10% and appears to be
      rising. A gradual decline in immune function, termed immunosenescence, and age
      related changes in tissue structure influence the development of these disorders.
      Common complications are comorbidities, polypharmacy, and adverse effects of
      drugs. The elderly have difficulty mounting protective immune responses against
      newly encountered antigens. The integrity of epithelial barriers is compromised,
      leading to a chronic, subclinical inflammatory state and an enhanced Th2
      (allergic) immune response. Undiagnosed asthma is frequent in elderly persons
      (about 8%) and still more commonplace in those with respiratory symptoms. Poorly
      controlled asthma in the elderly undermines their functional status and leads to
      a loss of autonomy and social isolation that may delay seeking medical services.
      Aggravation of allergic rhinitis coincides with exacerbation of asthma, whereas
      treatment of nasal inflammation improves control of the asthma. Atopic dermatitis
      is a chronically relapsing inflammatory skin disease often associated with
      respiratory allergy.

PMID- 24334921
TI  - Evaluation of weight loss and adipocytokine levels after two hypocaloric diets
      with different macronutrient distribution in obese subjects with the rs6923761
      gene variant of glucagon-like peptide 1 receptor.
AB  - BACKGROUND: The role of glucagon-like peptide-1 receptor (GLP-1R) variants on
      body weight response after dietary intervention has not been evaluated so far.
      OBJECTIVE: Our aim was to evaluate weight loss and adipocytokine levels after two
      hypocaloric diets with different macronutrient distribution in obese subjects
      with rs6923761. DESIGN: A sample of 280 obese subjects was randomized to two
      hypocaloric diets. RESULTS: 124 patients (44.3%) had the genotype GG (wild-type)
      and 156 (55.7%) had another genotype (mutant), i.e. GA (n = 132, 47.1%) or AA (n
      = 24, 8.6%). With the type I diet (low in carbohydrates) in the wild-type and
      mutant groups, BMI, weight, fat mass, waist circumference, insulin levels,
      insulin resistance and triglycerides decreased. Anthropometric parameters were
      higher in non-A-allele carriers than A-allele carriers. With the type II diet
      (low in fats) in all genotypes, BMI, weight, fat mass, waist circumference,
      insulin levels, total cholesterol and LDL cholesterol decreased. CONCLUSION: Our
      data showed better anthropometric parameters in obese subjects with the mutant
      allele (A) of the rs6923761 GLP-1R polymorphism. A lack of association of this
      polymorphism with weight loss or biochemical parameters after two different
      hypocaloric diets was observed.

PMID- 24334922
TI  - Loss of cellular cohesion in cytology composes a special subgroup of breast
      tumors - analysis of 37 cases.
AB  - OBJECTIVE: We analyzed smears by fine needle aspiration (FNA) from 37 cases that
      displayed numerous dissociated cells and correlated the results with histological
      findings. STUDY DESIGN: Between 1996 and 2005, 1,583 patients underwent breast
      FNA and resection. Loss of cellular cohesion was observed in 37 of these cases.
      RESULTS: From the cytological findings, we classified cases into 3 groups
      according to cell size and shape. Type A: numerous isolated spindle cells with a
      necrotic background. Four cases were classified into this group (3 cases of
      intraductal papilloma and 1 case of adenomyoepithelioma). Type B: lymphocytes and
      large isolated cells such as medullary carcinoma. Five cases were classified into
      this group [1 case of classic medullary carcinoma, 1 case of ductal carcinoma in
      situ (DCIS) and 3 cases of invasive carcinoma of no special type (NST)]. Type C:
      numerous uniform small round cells. Twenty-eight cases were classified into this
      group (2 cases of lobular carcinoma, 1 case of DCIS, 22 cases of invasive
      carcinoma NST, and 3 cases of solid papillary carcinoma). CONCLUSION: Numerous
      isolated cells are sometimes seen in both benign and malignant cytology.

PMID- 24334923
TI  - [Using reprogramming techniques of human somatic cells to understand genetic risk
      variations associated with psychiatric disorders].

PMID- 24334924
TI  - [Strategy of target validation from a novel risk factor of schizophrenia /
      bipolar disorder].

PMID- 24334925
TI  - [Cuprizone short-term exposure: glial activation and psychosis-like behavior].

PMID- 24334926
TI  - [Pharmacological characterization of metabotropic glutamate-receptor 1 antagonist
      for the treatment of schizophrenia].

PMID- 24334927
TI  - [Superoxide-generating enzymes NADPH oxidases, potential targets of drug therapy:
      various mechanisms for regulation of their expression].

PMID- 24334928
TI  - [Role of glutamate transporters in the pathophysiology of major mental
      illnesses].

PMID- 24334929
TI  - [Finding solutions for drug discovery in academia].

PMID- 24334930
TI  - [Quality characteristics and non-clinical/clinical profile of Filgrastim BS
      injection syringe "Mochida"/"F"].

PMID- 24334931
TI  - [Hypothalamic orexin system regulates energy and glucose metabolism].

PMID- 24334932
TI  - [Verification of mutational analysis of NCX by eukaryotic CaCA crystal
      structure].

PMID- 24334933
TI  - [Direct regulation of ion channel by PIP2].

PMID- 24334934
TI  - Killing two birds with one stone: screening of coronary artery disease and
      cardiac autonomic dysfunction in psoriasis.

PMID- 24334935
TI  - Etiological diversity of diarrhoeal disease in Bangladesh.
AB  - BACKGROUND: This study compared the diversity of common diarrhoeal pathogens and
      antimicrobial susceptibility in four hospitals in Bangladesh. METHODOLOGY: A
      total of 13,959 diarrhoea patients, comprising rural Mirzapur (2,820), rural
      Matlab (2,865), urban Dhaka (5,287) and urban Mirpur (2,987) were included under
      the diarrhoeal disease surveillance system of icddr,b during 2010-2011; stool
      specimens were tested for Shigella spp., Vibrio cholerae, enterotoxigenic
      Escherichia coli and rotavirus. RESULTS: Rotavirus was highest in Mirzapur (28%)
      followed by Dhaka (24%), Matlab (19%) and Mirpur (18%). Overall, Shigella was
      significantly more prevalent in rural sites (Mirzapur 13% and Matlab 7%), than in
      urban sites (Dhaka 3% and Mirpur 3%). Vibrio cholerae was more common in the
      urban sites of Dhaka (14%) and Mirpur (12%). 72% of Shigella isolates were
      susceptible to ciprofloxacin in Mirzapur, and 88% to mecillinam. In Dhaka, the
      figures for Shigella were 65% and 50%, in Matlab 65% and 85%, and in Mirpur 59%
      and 92% respectively. Susceptibility of Shigella to azithromycin and ceftriaxone
      in Dhaka was 74% and 95%, and in Mirpur 88% and 92% respectively.  Vibrio
      cholerae showed the highest resistance to trimethoprim-sulfamethoxazole (100% in
      Mirpur) and lowest resistance to ciprofloxacin (0% in Dhaka, Matlab and Mirpur)
      and azithromycin (30% in Dhaka to 7% in Mirzapur). Multidrug resistance (>=3
      antibiotics) for Shigella were: Mirzapur (50%); Dhaka (36%); Matlab (23%) and
      Mirpur (37%); and for V. cholerae it was 26%, 37%, 49% and 23% respectively.
      CONCLUSION: The isolation rates and antimicrobial susceptibility of Shigella spp.
      and V. cholerae along with rotavirus differed significantly in certain
      geographical sites.

PMID- 24334936
TI  - A cluster of cholera among patients in a Vietnamese district hospital in 2010.
AB  - On July 20, 2010, three cases of cholera were reported from a district hospital
      in Ca Mau province, Vietnam. We investigated the likely source and mode of
      transmission of the outbreak. All hospitals in the province were requested to
      notify cases of acute watery diarrhoea. Epidemiological, clinical, and laboratory
      data were collected. Between July 12 and 22, seven cases with positive culture
      for Vibrio cholera were identified. Six cases were epidemiologically linked to
      the index case. Basic infection control practices were not in place at the
      hospital. Clinicians and public health staff should consider the possibility of
      nosocomial cholera transmission even in non-endemic areas. 

PMID- 24334937
TI  - Long term effect of infection control practices and associated factors during a
      major Clostridium difficile outbreak in Costa Rica.
AB  - INTRODUCTION: The C. difficile BI/NAP 1 hyper virulent strain has been
      responsible for the nosocomial outbreaks in several countries. The present study
      describes the infection control strategies utilized to achieve outbreak control
      as well as the factors associated with a C. difficile BI/NAP 1 hyper virulent
      strain outbreak in Costa Rica. METHODOLOGY: A descriptive analysis of the C.
      difficile outbreak was completed for the period of January 2007 to December 2010
      in one affected hospital. An unmatched case-control study was subsequently
      performed to evaluate the association of exposure factors with C. difficile
      infection. RESULTS: The pattern of the outbreak was characterized by a sharp
      increase in the incidence rate during the initial weeks of the outbreak, which
      was followed by a reduction in the incidence curve as several infection control
      measures were implemented. The C. difficile BI/NAP1 infection was associated with
      the prescription of antibiotics, in particular levofloxacin (OR: 9.3; 95%CI: 2.1
      40.2), meropenem (OR: 4.9, 95%CI: 1.0-22.9), cefotaxime (OR: 4.3, 95%CI: 2.4
      7.7), as well as a medical history of diabetes mellitus (OR: 2.9, 95%CI: 1.5
      5.8). CONCLUSIONS: The infection control strategies implemented proved to be
      effective in achieving outbreak control and in maintaining the baseline C.
      difficile incidence rate following it. The reported C. difficile outbreak was
      associated with the prescription of broad-spectrum antibiotics and a medical
      history of diabetes.

PMID- 24334938
TI  - The characterization of ESBL genes in Escherichia coli and Klebsiella pneumoniae
      causing nosocomial infections in Vietnam.
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) are enzymes capable of
      hydrolyzing oxyimino-beta-lactams and inducing resistance to third generation
      cephalosporins. The genes encoding ESBLs are widespread and generally located on
      highly transmissible resistance plasmids. We aimed to investigate the complement
      of ESBL genes in E. coli and Klebsiella pneumoniae causing nosocomial infections
      in hospitals in Ho Chi Minh City, Vietnam. METHODOLOGY: Thirty-two non-duplicate
      isolates of E. coli and Klebsiella pneumoniae causing nosocomial infections,
      isolated between March and June 2010, were subjected to antimicrobial
      susceptibility testing. All isolates were PCR-amplified to detect the blaSHV,
      blaTEM and blaCTX-M ESBL genes and subjected to plasmid analysis. RESULTS: We
      found that co-resistance to multiple antimicrobials was highly prevalent, and we
      report the predominance of the blaCTX-M-15 and blaCTX-M-27 genes, located on
      highly transmissible plasmids ranging from 50 to 170 kb in size. CONCLUSIONS: Our
      study represents a snap shot of ESBL-producing enteric bacteria causing
      nosocomial infections in this setting. We suggest that antimicrobial resistance
      in nosocomial E. coli and Klebsiella pneumoniae is rampant in Vietnam and ESBL
      organisms are widespread. In view of these data and the dramatic levels of
      antimicrobial resistance reported in Vietnam we advocate an urgent review of
      antimicrobial use in the Vietnamese healthcare system.

PMID- 24334939
TI  - Molecular evaluation of drug resistance in clinical isolates of Salmonella
      enterica serovar Typhi from Pakistan.
AB  - INTRODUCTION: This study aimed to determine the drug susceptibility patterns and
      genetic elements related to drug resistance in isolates of Salmonella enterica
      serovar Typhi (S. Typhi) from the Faisalabad region of Pakistan. METHODOLOGY: The
      drug resistance status of 80 isolates were evaluated by determining antimicrobial
      susceptibility, MICs, drug resistance genes involved, and the presence of
      integrons. Nalidixic acid resistance and reduced susceptibility to ciprofloxacin
      were also investigated by mutation screening of the gyrA, gyrB, parC, and parE
      genes. RESULTS: Forty-seven (58.7%) isolates were multidrug resistant (MDR).
      Among the different resistance (R) types, the most commonly observed (13/80) was
      AmChStrTeSxtSmzTmp, which is the most frequent type observed in India and
      Pakistan. The most common drug resistant genes were blaTEM-1, cat, strA-strB,
      tetB, sul1, sul2, and dfrA7. Among the detected genes, only dfrA7 was found to be
      associated in the form of a single gene cassette within the class 1 integrons.
      CONCLUSIONS: MIC determination of currently used drugs revealed fourth-generation
      gatifloxacin as an effective drug against multidrug-resistant S. Typhi, but its
      clinical use is controversial. The Ser83->Phe substitution in gyrA was the
      predominant alteration in nalidixic acid-resistant isolates, exhibiting reduced
      susceptibility and increased MICs against ciprofloxacin. No mutations in gyrB,
      parC, or parE were detected in any isolate.

PMID- 24334940
TI  - Usefulness of real-time PCR assay targeting lipL32 gene for diagnosis of human
      leptospirosis in Uruguay.
AB  - INTRODUCTION: Assays based on DNA amplification can provide information that
      contributes to the initial management of patients with leptospirosis. However,
      these have not been adopted in Uruguay. Our aim was to evaluate the performance
      of the lipL32 real-time PCR (qPCR) for diagnosis of leptospirosis. METHODOLOGY:
      We analyzed by microscopic agglutination test (MAT) and lipL32 qPCR serum samples
      from 183 patients with suspected leptospirosis. To establish the analytical
      sensitivity of the qPCR, experimentally spiked samples with known amounts of
      Leptospira interrogans were analyzed. RESULTS: The analytical sensitivity of the
      qPCR was 102 leptospires/mL. In 98 patients MAT results were negative meanwhile
      85 showed positive reactions, revealing acute infections. Twenty six acute-phase
      sera of these 85 patients showed a positive signal by qPCR (diagnostic
      sensitivity 30%). In these patients the average time between onset of symptoms
      and collection of the first sample was 8 days. In patients with negative results
      for qPCR and positive MAT results (n=59) the average interval between onset of
      symptoms and collection of the first sample was 13 days. The qPCR did not yield
      false positive results. CONCLUSIONS: The qPCR had a lower diagnostic sensitivity
      than MAT and a higher cost. However, it allowed to make an early diagnosis in 26
      patients. In patients with confirmed acute infections and negative results by
      qPCR, more than 8 days had elapsed between the onset of the illness and
      extraction of the first serum sample. Our data support that the qPCR from sera
      have clinical utility within the first week of illness.

PMID- 24334941
TI  - Seroprevalence of parvovirus B19 IgG and IgM antibodies among pregnant women in
      Oyo State, Nigeria.
AB  - INTRODUCTION: Human parvovirus B19 causes a wide range of complications in
      pregnant women including abortion, severe fetal anemia, non-immune hydrops
      fetalis, and even intrauterine fetal death. However, there is a dearth of
      information on the prevalence of the virus among pregnant women in southwestern
      Nigeria. METHODOLOGY: Blood samples were collected from 231 pregnant women and
      screened for antibodies to human parvovirus B19 IgM and IgG using an enzyme
      immunosorbent assay kits. RESULTS: Of the 231 women, 31 were in their first
      trimester, 146 were in their second trimester, and 54 were in their third
      trimester. Forty-five (20%) were positive for parvovirus B19 IgG antibodies, 10
      (4%) were positive for parvovirus B19 IgM antibodies, and 176 (76%) had no
      detectable parvovirus B19 antibodies. Twenty-eight (19%) of the 146 pregnant
      women in their second trimester were positive for parvovirus B19 IgG antibody
      while three (2%) of the 146 were positive for parvovirus B19 IgM antibody.
      CONCLUSIONS: It is evident that there is a high prevalence of human parvovirus
      B19 among pregnant women in south-western Nigeria. This suggests that there is an
      active transmission of the virus in the community; it is therefore necessary to
      conduct more studies on the virus in pregnant women in Nigeria to ascertain its
      effect on the fetus.

PMID- 24334942
TI  - Prevalence of hepatitis B e antigen among human immunodeficiency virus and
      hepatitis B virus co-infected patients in Jos, Nigeria.
AB  - INTRODUCTION: Human immunodeficiency virus (HIV) negatively impacts the natural
      history of hepatitis B virus (HBV) infection, including replication. We
      determined the prevalence of HBeAg in HIV/HBV co-infected patients compared to
      HBV mono-infected controls and further investigated the relationship between
      HBeAg seropositivity and the degree of HIV-induced immunosuppression in co
      infected patients. METHODOLOGY: The study design was cross-sectional. One hundred
      HBsAg-positive HIV-infected adults and 100 age and sex matched HBsAg-positive HIV
      negative controls were consecutively recruited between May and November 2010.
      Relevant demographic and HBV-related information was obtained. HBeAg was assayed
      by semi-quantitative third generation ELISA. The HIV/HBV co-infected patients
      also had CD4+ cell and HIV viral load quantification measured using flow
      cytometry and polymerase chain reaction techniques respectively. RESULTS: In each
      group, the mean age was 34 +/- 8 years and the majority (61%) was female. The
      prevalence of HBeAg was significantly higher among co-infected patients (n = 28;
      28%) than in the controls (n = 15; 15%; p = 0.03). HBeAg seropositivity was
      independently associated with age < 40 years (AOR = 2.83, 95% = CI 1.29-6.17) and
      HIV seropositivity (AOR = 2.44, 95% C.I = 1.17-5.07). The prevalence of HBeAg was
      significantly higher in co-infected patients with CD4 cell count < 200 cell/uL
      (41.3%) compared to those with 200-499 cell/uL (18.6%) and >=500 cell/uL (9.1%),
      p = 0.006. CONCLUSION: HIV/HBV co-infected patients have a significantly higher
      prevalence of HBeAg than HBV mono-infected individuals. HBV-infected patients
      should be routinely assessed for HBeAg, especially if they are co-infected with
      HIV.

PMID- 24334943
TI  - Hepatitis B seroprevalence in children and women and the impact of the hepatitis
      B vaccination program in the Black Sea Region of Turkey.
AB  - INTRODUCTION: This study aimed to determine the seroprevalence of hepatitis B
      virus (HBV) infection in children and females in the middle Black Sea Region of
      Turkey and to assess the impact of the universal infant hepatitis B vaccination
      program started in 1998. METHODOLOGY: The laboratory records of 12,057 patients
      who attended the Samsun Maternity and Children's Hospital between January 2007
      and November 2009 were evaluated retrospectively. In this period, hepatitis B
      surface antigen (HBsAg), the antibody to hepatitis B surface antigen (anti-HBs),
      was studied from serum samples using the enzyme linked immunosorbent assay
      method. RESULTS: In the total population, HBsAg seropositivity was found to be
      3.8% (456/12010); anti-HBs was 32.6% (3526/10800). HBsAg was 3.5%, in the 0-14
      year age group, 8.2% in the 15-18 group, 3.3% in the 19-49 group, and 8.0% in the
      over 49 group. The seropositivity of HBsAg decreased by half in patients between
      zero and 14 years of age (4.2%) who were included in the universal vaccination
      program when compared with those in the 15-18 year group (8.2%) who were not
      included in the program. There was a significant difference in HBsAg
      seropositivity between boys (5.8%) and girls (3.9%) (p <0.05). CONCLUSIONS:
      According to the hepatitis B seroprevalence records of our region, HBsAg was 3.5%
      in the 0-14 year age group, 8.2% in the 15-18 year group. It may therefore be
      suggested that, since 1998, the vaccination program in our region has been
      successful.

PMID- 24334944
TI  - Sexual behaviors and awareness of sexually transmitted infections among Chinese
      university students.
AB  - INTRODUCTION: This study investigated the current state of attitudes, behaviors,
      and knowledge concerning sex and sexually transmitted infections (STIs) among
      Chinese university students. METHODOLOGY: A cross-sectional anonymous university
      intranet-based survey was given to students attending the Shantou University,
      Guangdong, China using a 28-item questionnaire. RESULTS: Of 3425 website
      visitors, 1030 university students completed the survey, of which 80% were
      between 20 and 25 years of age, 76% considered pre-marital sex acceptable, 21%
      had had sexual intercourse, and 45% of sexually active students had engaged in
      oral sex, anal intercourse, or sex with strangers. Students had limited knowledge
      and awareness about common STIs, symptoms, and complications. Three percent of
      the sexually active students reported having had STIs and another 8% were not
      sure whether they had or not. Most students had misconceptions about transmission
      and prevention of STIs. The internet was the main information resource for 76% of
      students. CONCLUSIONS: Despite having more open attitudes and behaviors towards
      sex, students' STI knowledge and awareness of STI risks was considerably limited,
      raising concerns about a likely rise in STI incidence. Prior knowledge of STIs
      had no significant influence. Targeted educational measures such as online
      education and counseling via Chinese websites and social media, and the provision
      of safer sex and STI-related information by health experts to university students
      are suggested.

PMID- 24334945
TI  - Efficacy of artemisinin combination therapy for the treatment of uncomplicated
      falciparum malaria in Nigerian children.
AB  - INTRODUCTION: The development and spread of Plasmodium falciparum resistance to
      most commonly used antimalarials remain a major challenge in the control of
      malaria. Constant monitoring of drug efficacy is an important tool in
      establishing rational antimalarial drug policies. METHODOLOGY: A randomized
      comparative study was conducted at the Wesley Guild Hospital, Ilesa, Nigeria
      between February 2010 and September 2011 comparing the efficacy and safety of
      artemether-lumefantrine (Coartem) and fixed dose of artesunate plus amodiaquine
      (Larimal) in the treatment of uncomplicated P. falciparum malaria in children
      betweem 6 and 144 months of age. P. falciparum malaria parasitemia was assessed
      by microscopy and rapid diagnostic test. Drugs were administered according to age
      for three days under supervision. The primary efficacy endpoint was a day 28 PCR
      corrected parasitological cure. RESULTS: A total of 182 patients were enrolled in
      the two treatment groups, Coartem (n = 101) and Larimal (n = 81), and tested
      after 28 days. In the intention-to-treat population, Coartem (n = 101) and
      Larimal (n = 81) had a PCR-corrected cure rate of 98% and 100% respectively,
      while in the per-protocol population, Coartem (n = 89) and Larimal (n = 71) both
      had a PCR-corrected cure rate of 100% at day 28. Although parasite and fever
      clearance time was faster in the Larimal group, no significant difference was
      observed between the two drugs. No serious adverse effects  were reported.
      CONCLUSION: Five years after being introduced in Nigeria, both Coartem and
      Larimal have been shown to be safe and highly effective in the treatment of
      uncomplicated P. falciparum malaria in children.

PMID- 24334946
TI  - Anaemia and severe malarial anaemia burden in febrile Gabonese children: a nine
      year health facility based survey.
AB  - INTRODUCTION: Anaemia remains a major cause of poor health in children and
      pregnant women living in sub-Saharan Africa. Malaria is one of the main causes of
      anaemia in endemic countries. At the time of decreasing Plasmodium falciparum
      infection prevalence among children, it was essential to analyze the evolution of
      anaemia and severe malarial anaemia (SMA), the most frequent clinical
      manifestation of severe malaria, in Gabon. METHODOLOGY: Yearly recorded
      haemoglobin levels of febrile children aged below11 years, who benefitted from
      microscopic malaria diagnosis, were retrospectively analyzed to determine the
      evolution of anaemia and SMA prevalence throughout a nine-year period between
      2000 and 2008. RESULTS: Anaemia prevalence remained high both in P. falciparum
      infected children (between 87.6% and 90.7%) and in uninfected children (between
      73.5% and 82.6%). Although the risk of developing severe anaemia ranged between
      1.9 [0.9-3.8] in 2000 and 3.0 [1.3-6.5] in 2007, SMA prevalence did not
      significantly change during the study period, varying from 6.0% to 8.0%. From
      2001, the frequency of SMA was comparable between children younger than five
      years of age and children older than five years of age. CONCLUSIONS: The
      decreasing malaria prevalence previously observed in Gabon between 2000 and 2008
      was not associated with a significant reduction of anaemia and SMA burden among
      children. Furthermore, other factors such as nutritional deficiencies, which may
      not be negligible, must be investigated in this vulnerable population.

PMID- 24334947
TI  - Point prevalence survey of antimicrobial utilization in oncology patients.
AB  - INTRODUCTION: Point prevalence surveys have been used internationally to
      characterize the use of antimicrobial agents. The primary objective of this study
      was to determine prevalence of antimicrobial use in the oncology population in
      Qatar. METHODOLOGY: Data was collected from the National Center for Cancer Care
      and Research hospital over 3 separate days during a two week period. Adults
      admitted on the day of audit were included. RESULTS: Prevalence of antimicrobial
      use during the audit was 43% (25/58). The most commonly prescribed class of
      antimicrobial agents was penicillin/Beta-lactamase inhibitor combinations 39.4%
      (13/33). CONCLUSIONS: Findings demonstrate frequent antimicrobial consumption of
      broad spectrum antimicrobial agents which highlights the importance of expanding
      antimicrobial stewardship programs in this population.

PMID- 24334948
TI  - Poor compliance with the antibiotic policy in the intensive care unit (ICU) of a
      tertiary care hospital in India.
AB  - INTRODUCTION: Most developing countries are adopting antibiotic policies to
      contain the acute problem of drug resistance; however, several obstacles prevent
      their fulfillment. This study was undertaken to prospectively determine the
      compliance with the antibiotic policy in the intensive care unit (ICU) of a
      tertiary care hospital and possible reasons for non-compliance. METHODOLOGY:
      Compliance with the newly introduced antibiotic policy was studied for a period
      of six months. A total of 170 cases from the ICU were included. Relevant
      information regarding patient characteristics, treatment details, infection
      control, and antibiotic prescribing practices in the ICU with reference to the
      antibiotic policy was collected. Reasons for non-compliance were studied.
      RESULTS: The rate of compliance with the antibiotic policy was 21.18%. Heavy use
      of antibiotics prior to the time of admission in the ICU was the major cause of
      non-compliance. Microbiological investigation had been sent in only 51.17% of the
      cases and change in treatment protocol based on culture report was done in 53.3%.
      The rate of use of third-generation cephalosporins was 76.78%. CONCLUSIONS: We
      found non-compliance with the antibiotic policy in the ICU mainly due to improper
      and inappropriate antibiotic usage in other indoor units of the hospital. In our
      case, a policy covering the entire hospital is required to meet the goals of
      antibiotic usage restriction. An effective surveillance, review, and evaluation
      process should be an integral part of the policy, even in developing countries,
      to measure the effects of such policies.

PMID- 24334949
TI  - Serological evidence of West Nile Virus infection among humans in the southern
      Provinces of Morocco.
AB  - INTRODUCTION: The objective of this study was to determine the prevalence of West
      Nile Virus infection in the southern provinces of Morocco. METHODOLOGY: A total
      of 250 sera, collected during 2012 in the province of Dakhla, were analyzed by
      microneutralisation assay. RESULTS: WNV-neutralizing antibodies were detected in
      13 samples (5.2%). The participants with WNV-specific antibodies were
      significantly younger than the rest of the population (p = 0.009). The positivity
      rate was higher among women (6.3%) than men (3.6%) (p = 0.26). CONCLUSIONS: This
      is the first serological evidence of WNV infection among humans in the southern
      provinces of Morocco.

PMID- 24334950
TI  - Cytomegalovirus reactivation following hematopoietic stem cell transplantation.
AB  - INTRODUCTION: There is a high prevalence of cytomegalovirus (CMV) seropositivity
      in developing countries. An apparent risk of CMV reactivation increases following
      hematopoeitic stem cell transplantation. With effective surveillance and timely
      treatment using anti-viral therapy, morbidity and mortality associated with CMV
      reactivation can be reduced. OBJECTIVES: To evaluate the incidence and morbidity
      associated with CMV reactivation following hematopoeitic stem cell
      transplantation. METHODOLOGY: We retrospectively analysed 136 hematopoeitic stem
      cell transplant recipients at our centre for CMV reactivation and their
      complications. Quantification of CMV-DNA was done by PCR. CMV disease was
      confirmed histologically via CMV inclusion bodies or immunostaining of biopsy of
      the affected organ, mainly the gastrointestinal tract. RESULTS: A total of 13 out
      of 136 patients (9.56%) had CMV reactivation. 6 out of 13 patients had CMV
      disease, 3 of which died (23.1% of patients with CMV reactivation). CMV
      reactivation occurred at a median duration of 52.5 days post transplantation
      (range 35-178 days). The gastrointestinal tract was the organ most commonly
      affected by CMV. The median follow-up was 14 months (range 6 - 64 months).
      CONCLUSION: Through a higher rate of sero-prevalance in developing countries, the
      incidence of CMV infection following hematopoeitic stem cell transplantation is
      comparable to that reported in Western literature. Oral valganciclovir was an
      effective pre-emptive therapy for CMV disease.

PMID- 24334951
TI  - A case of brucellosis displaying Parkinsonian-like tremor.
AB  - We report a rare case of brucellosis with Parkinsonian-like tremor and simple
      partial motor seizure. This patient worked as a sheep butcher and the sheep were
      imported from brucellosis-endemic areas. He presented with classical
      manifestations of brucellosis; infection was confirmed using the Rose Bengal
      Plate and Standard Tube Agglutination tests. The patient also suffered from
      headache, partial seizures, changes of personality and static tremor of both
      upper limbs. After anti-infection therapy, but without the use of anti-Parkinson
      drugs, the patient fully recovered and remained free of Parkinsonian-like tremor.
      Brucellosis can present with atypical symptoms, clinicians should widen their
      diagnostic view of brucella infection. 

PMID- 24334952
TI  - Thrombocytosis and small bowel perforation: unusual presentation of
      abdominopelvic actinomycosis.
AB  - Intrauterine devices (IUD) are frequently used as a family planning procedure in
      developing countries because they are easy to administer and governmental
      policies support their use in many countries. It is recommended that IUDs be
      removed or replaced after 10 years, but longer use is common, especially in
      developing countries. In some cases, rare infections such as pelvic inflammatory
      diseases, pelvic tuberculosis, or abdominopelvic actinomycosis related to IUD can
      develop. Pelvic actinomycosis is a rare disease and is often diagnosed
      incidentally during surgery. In recent years, there has been an increase in
      actinomycotic infections mostly due to long-term usage of IUD and forgotten
      intravaginal pessaries. It usually develops as an ascending infection. It is
      usually associated with non-specific symptoms such as lower abdominal pain,
      menstrual disturbances, fever, and vaginal discharge. The disease is sometimes
      asymptomatic. The rate of accurate preoperative diagnosis for pelvic
      actinomycosis is less than 10%, and symptoms and imaging studies sometimes mimic
      pelvic malignancy. This report details a case with abdominopelvic actinomycosis
      associated with an IUD presenting with highly elevated thromboctye count and
      small bowel perforation with abscess formation. 

PMID- 24334953
TI  - ESBL-producing E. coli and K. pneumoniae in Al-Ahsa, Saudi Arabia: antibiotic
      susceptibility and prevalence of blaSHV and blaTEM.

PMID- 24334954
TI  - Molecular identification of Cryptosporidium spp. from animal sources in China.

PMID- 24334955
TI  - Compromised telomere maintenance in hypomethylated Arabidopsis thaliana plants.
AB  - Telomeres, nucleoprotein structures at the ends of linear eukaryotic chromosomes,
      are important for the maintenance of genomic stability. Telomeres were considered
      as typical heterochromatic regions, but in light of recent results, this view
      should be reconsidered. Asymmetrically located cytosines in plant telomeric DNA
      repeats may be substrates for a DNA methyltransferase enzyme and indeed, it was
      shown that these repeats are methylated. Here, we analyse the methylation of
      telomeric cytosines and the length of telomeres in Arabidopsis thaliana
      methylation mutants (met 1-3 and ddm 1-8), and in their wild-type siblings that
      were germinated in the presence of hypomethylation drugs. Our results show that
      cytosine methylation in telomeric repeats depends on the activity of MET1 and
      DDM1 enzymes. Significantly shortened telomeres occur in later generations of
      methylation mutants as well as in plants germinated in the presence of
      hypomethylation drugs, and this phenotype is stably transmitted to the next plant
      generation. A possible role of compromised in vivo telomerase action in the
      observed telomere shortening is hypothesized based on telomere analysis of
      hypomethylated telomerase knockout plants. Results are discussed in connection
      with previous data in this field obtained using different model systems. 

PMID- 24334956
TI  - Overexpression of FGF9 in colon cancer cells is mediated by hypoxia-induced
      translational activation.
AB  - Human fibroblast growth factor 9 (FGF9) is a potent mitogen involved in many
      physiological processes. Although FGF9 messenger RNA (mRNA) is ubiquitously
      expressed in embryos, FGF9 protein expression is generally low and restricted to
      a few adult organs. Aberrant expression of FGF9 usually results in human
      malignancies including cancers, but the mechanism remains largely unknown. Here,
      we report that FGF9 protein, but not mRNA, was increased in hypoxia. Two sequence
      elements, the upstream open reading frame (uORF) and the internal ribosome entry
      site (IRES), were identified in the 5' UTR of FGF9 mRNA. Functional assays
      indicated that FGF9 protein synthesis was normally controlled by uORF-mediated
      translational repression, which kept the protein at a low level, but was
      upregulated in response to hypoxia through a switch to IRES-dependent
      translational control. Our data demonstrate that FGF9 IRES functions as a
      cellular switch to turn FGF9 protein synthesis 'on' during hypoxia, a likely
      mechanism underlying FGF9 overexpression in cancer cells. Finally, we provide
      evidence to show that hypoxia-induced translational activation promotes FGF9
      protein expression in colon cancer cells. Altogether, this dynamic working model
      may provide a new direction in anti-tumor therapies and cancer intervention. 

PMID- 24334957
TI  - The Transformer database: biotransformation of xenobiotics.
AB  - As the number of prescribed drugs is constantly rising, drug-drug interactions
      are an important issue. The simultaneous administration of several drugs can
      cause severe adverse effects based on interactions with the same metabolizing
      enzyme(s). The Transformer database
      (http://bioinformatics.charite.de/transformer) contains integrated information on
      the three phases of biotransformation (modification, conjugation and excretion)
      of 3000 drugs and >350 relevant food ingredients (e.g. grapefruit juice) and
      herbs, which are catalyzed by 400 proteins. A total of 100,000 interactions were
      found through text mining and manual validation. The 3D structures of 200
      relevant proteins are included. The database enables users to search for drugs
      with a visual display of known interactions with phase I (Cytochrome P450) and
      phase II enzymes, transporters, food and herbs. For each interaction, PubMed
      references are given. To detect mutual impairments of drugs, the drug-cocktail
      tool displays interactions between selected drugs. By choosing the indication for
      a drug, the tool offers suggestions for alternative medications to avoid
      metabolic conflicts. Drug interactions can also be visualized in an interactive
      network view. Additionally, prodrugs, including their mechanisms of activation,
      and further information on enzymes of biotransformation, including 3D models, can
      be viewed.

PMID- 24334958
TI  - Mucosa-associated lymphoid tissue (MALT) lymphoma presenting as subglottic
      stenosis: single-agent treatment using rituximab.

PMID- 24334959
TI  - Physician knowledge of and attitudes toward the Patient Protection and Affordable
      Care Act.
AB  - OBJECTIVE: To assess otolaryngology physician knowledge of and attitudes toward
      the Patient Protection and Affordable Care Act (PPACA) and compare the
      association of bias toward the PPACA with knowledge of the provisions of the
      PPACA. STUDY DESIGN: Cross-sectional survey. SETTING: Nationwide assessment.
      SUBJECTS: Members of the American Academy of Otolaryngology-Head and Neck
      Surgery. METHODS: Otolaryngology physicians answered 10 true/false questions
      about major provisions of the PPACA. They also indicated their level of agreement
      with 9 statements about health care and the PPACA. Basic demographic information
      was collected. RESULTS: Email solicitation was sent to 9972 otolaryngologists and
      647 responses were obtained (6.5% response rate). Overall correct response rate
      was 74%. Fewer than 60% of physicians correctly answered questions on whether
      small businesses receive tax credits for providing health insurance, the effect
      of the PPACA on Medicare benefits, and whether a government-run health insurance
      plan was created. Academic center practice setting, bias toward the PPACA, and
      Democratic Party affiliation were associated with significantly more correct
      responses. CONCLUSION: Overall physician knowledge of the PPACA is assessed as
      fair, although better than the general public in 2010. There are several areas
      where knowledge of physicians regarding the PPACA is poor, and this knowledge
      deficit is more pronounced within certain subgroups. These knowledge issues
      should be addressed by individual physicians and medical societies.

PMID- 24334960
TI  - Microbiological sampling of the forgotten components of a flexible fiberoptic
      laryngoscope: what lessons can we learn?
AB  - The effectiveness of a Cidex-based decontamination protocol was analyzed for its
      effectiveness in cleaning various components of a flexible fiberoptic
      laryngoscope (FFL), including the handle, eyepiece, and detachable light cable. A
      random microbiological sampling and aerobic bacterial culture analysis of 6 FFL
      eyepieces, 6 FFL driver handles, and 5 light cables prior to patient use was
      performed. Of 17 samples collected, 7 (41%) were contaminated with bacterial
      organisms. Organisms recovered represented both environmental organisms from skin
      and oral flora origin. This study demonstrates that potential contaminants may be
      present on FFL eyepieces and light cables, which are commonly overlooked in the
      cleaning protocols of a standard otolaryngology clinic. 

PMID- 24334961
TI  - Congenital perilymph fistula causing recurrent meningitis: lessons learnt from a
      single-institution case series.
AB  - OBJECTIVE: To study the steps involved in definitive evaluation and successful
      management of patients with congenital perilymph fistula presenting with
      recurrent meningitis. STUDY DESIGN: Case series with chart review. SETTING:
      Tertiary care center. SUBJECTS AND METHODS: The case records of 11 patients (12
      ears) treated for congenital perilymph fistula presenting with recurrent
      meningitis were reviewed to ascertain their clinical, radiological, and
      intraoperative features and outcome following surgery. RESULTS: Most patients
      presented after at least 3 episodes of meningitis (range, 2-10 episodes).
      Ipsilateral hearing loss was present in 9 of 12 ears, with normal hearing in 3
      patients. High-resolution computed tomography and/or magnetic resonance imaging
      scanning of the temporal bone contributed to the diagnosis in 75% of cases but
      was normal in 3 cases (25%). Oval window and round window defects were the most
      common (66.7% and 63.6%, respectively). Four ears (33.3%) had more than 1 defect.
      The unusual presentations included 2 patients who presented in adulthood, a
      patient with a defect in the medial wall of the attic, and 3 patients with normal
      radiological findings. Follow-up ranged from 1 to 11 years (median, 2 years).
      There were 2 failures following simple fistula closure with cessation of symptoms
      after vestibular obliteration. No patient was readmitted with recurrent
      meningitis after definitive surgery. CONCLUSION: Up to 25% of patients with
      recurrent meningitis secondary to congenital perilymph fistula may have normal
      audiological and radiological assessment necessitating exploratory tympanotomy.
      Vestibular obliteration, rather than simple fistula closure, prevents recurrence.

PMID- 24334962
TI  - Reflections on social activism in otolaryngology.
AB  - What is "social activism" to you? For older otolaryngologists, the term is likely
      to signify the tumult of the 1960s. For incoming generations, this connotation is
      outdated. Rather, it more broadly reflects concerted efforts to improve the
      public good. Some ally with existing institutions to work toward incremental
      progress. Some start new organizations, using technological tools to build
      networks, marshal resources, and leapfrog hurdles. Countering these efforts are
      the ever-changing challenges of practicing otolaryngology today: electronic
      health records, shifting incentives, and changes in the practice model.
      Employment by large conglomerates is more common, decreasing our visibility as
      community leaders. Burnout is a recognized "hazard," and budding
      otolaryngologists are particularly susceptible. Adding one more thing, like
      social activism, to a full plate seems counterintuitive. But it shouldn't be. You
      don't need a "bigger" plate to get involved in social causes. Start simple. Find
      a partner. Scale up. You'll find it rewarding. 

PMID- 24334963
TI  - Correlation between nasal anatomy and objective obstructive sleep apnea severity.
AB  - OBJECTIVES: To determine if a correlation exists between nasal anatomical
      obstruction and obstructive sleep apnea severity as measured by overnight
      polysomnogram (PSG). STUDY DESIGN: Cross-sectional study. SETTING: Tertiary
      medical center. SUBJECTS AND METHODS: Subjects were recruited immediately prior
      to an overnight, in-lab PSG. All subjects who agreed to participate underwent a
      standardized nasal examination performed by the senior author and then completed
      the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire, the Snore Outcomes
      Survey (SOS), and the Epworth Sleepiness Scale (ESS) prior to their sleep study.
      In addition, tonsil size, Mallampati score, Friedman tongue position, neck
      circumference, uvula length, and occlusion were assessed and documented. Nasal
      anatomy assessments were then compared with PSG, NOSE, SOS, and ESS results.
      Bonferroni correction was used to account for multiple comparisons. RESULTS: One
      hundred subjects were included in the study. Fifty-nine subjects (59%) were found
      to have obstructive sleep apnea syndrome (OSAS) (mean apnea-hypopnea index, 13.1;
      range, 0-64). Severity of OSAS was associated with age (Spearman's rho = 0.386, P
      = .0001). No single nasal anatomy measurement or combined nasal anatomy index was
      found to correlate with objective sleep-disordered breathing severity measured by
      PSG. The sample size should have provided 90% power to detect a significant
      correlation if one existed. After accounting for multiple comparisons, turbinate
      hypertrophy was found to correlate with the NOSE score (0.3577, P = .0305
      corrected), and external and internal nasal valve collapse correlated with each
      other (0.4986, P < .0001 corrected). CONCLUSIONS: Objectively assessed abnormal
      nasal anatomy was not found to be significantly correlated with PSG-measured OSAS
      severity. Specific objective measurements of obstructive nasal anatomy were
      correlated to subjective measures of nasal obstruction.

PMID- 24334964
TI  - Smoking status and severity of ischemic stroke. A population-based study.
AB  - We aimed to investigate the impact of smoking status on clinical severity in
      patients with ischemic stroke event (IS). Patients were prospectively identified
      among residents of the city of Dijon, France (ca. 151,000 inhabitants), using a
      population-based registry, between 2006 and 2011. Demographic and clinical data
      were recorded. The initial clinical severity was quantified by the means of the
      National Institutes of Health Stroke Scale (NIHSS). Multivariable ordinal
      logistic regression was used to assess the effect of smoking status on severity.
      Among the 1,056 recorded patients with IS, data about smoking status were
      available for 973 (92.1%), of whom 658 (67.3%) were non-smokers, 187 (19.2%) were
      current smokers, and 128 (13.2%) were former smokers. Compared with non-smoking,
      former smoking was associated with less severe IS (OR 0.55; 95% CI 0.38-0.82, p =
      0.003), whereas this association was not found for current smokers (OR 0.97; 95%
      CI 0.69-1.36, p = 0.856). Further work is needed to understand the underlying
      mechanisms of this finding.

PMID- 24334966
TI  - New genetic abnormalities in non-21alpha-hydroxylase-deficiency congenital
      adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia comprises a group of autosomal recessive disorders
      of sexual differentiation and development that occur due to deficiencies in
      steroidogenic enzymes within the adrenal gland. Using clinical, biochemical, and
      sequencing data, we describe non-21alpha-hydroxylase deficiencies in 6
      individuals from 4 families originating from endogamic regions in Mexico. Three
      individuals had 11beta- hydroxylase deficiencies caused by 2 hitherto unreported
      mutations (P442L substitution and an 11-bp insertion in exon 5 of CYP11B1), while
      3 individuals had 17alpha-hydroxylase/17,20-lyase deficiencies. Sequence-tagged
      site analysis of 8 individuals from 1 endogamic region suggested that the
      mutations likely occurred as a result of a founder effect. Although non-21alpha
      hydroxylase enzymatic defects are rare in most populations, characterization of
      new mutations is important in order to understand the demographic, clinical,
      biochemical, and molecular variations that exist, and for both active and
      preventative management in individuals and their communities.

PMID- 24334965
TI  - Clinical implications of referral bias in the diagnostic performance of exercise
      testing for coronary artery disease.
AB  - BACKGROUND: Exercise testing with echocardiography or myocardial perfusion
      imaging is widely used to risk-stratify patients with suspected coronary artery
      disease. However, reports of diagnostic performance rarely adjust for referral
      bias, and this practice may adversely influence patient care. Therefore, we
      evaluated the potential impact of referral bias on diagnostic effectiveness and
      clinical decision-making. METHODS AND RESULTS: Searching PubMed and EMBASE (1990
      2012), 2 investigators independently evaluated eligibility and abstracted data on
      study characteristics and referral patterns. Diagnostic performance reported in 4
      previously published meta-analyses of exercise echocardiography and myocardial
      perfusion imaging was adjusted using pooled referral rates and Bayesian methods.
      Twenty-one studies reported referral patterns in 49 006 patients (mean age 60.7
      years, 39.6% women, and 0.8% prior history of myocardial infarction).
      Catheterization referral rates after normal and abnormal exercise tests were 4.0%
      (95% CI, 2.9% to 5.0%) and 42.5% (36.2% to 48.9%), respectively, with odds ratio
      for referral after an abnormal test of 14.6 (10.7 to 19.9). After adjustment for
      referral, exercise echocardiography sensitivity fell from 84% (80% to 89%) to 34%
      (27% to 41%), and specificity rose from 77% (69% to 86%) to 99% (99% to 100%).
      Similarly, exercise myocardial perfusion imaging sensitivity fell from 85% (81%
      to 88%) to 38% (31% to 44%), and specificity rose from 69% (61% to 78%) to 99%
      (99% to 100%). Summary receiver operating curve analysis demonstrated only modest
      changes in overall discriminatory power but adjusting for referral increased
      positive-predictive value and reduced negative-predictive value. CONCLUSIONS:
      Exercise echocardiography and myocardial perfusion imaging are considerably less
      sensitive and more specific for coronary artery disease after adjustment for
      referral. Given these findings, future work should assess the comparative ability
      of these and other tests to rule-in versus rule-out coronary artery disease.

PMID- 24334967
TI  - Comparison of normal- and high-tension glaucoma: nerve fiber layer and optic
      nerve head damage.
AB  - PURPOSE: The aim of this study was to investigate differences in the nerve fiber
      layer and glaucoma-induced structural optic nerve head (ONH) damage in patients
      with normal- (NTG) and high-tension (HTG) glaucoma. METHODS: In this
      retrospective pair-matched comparative study, 22 NTG and 22 HTG eyes were matched
      according to the same glaucomatous damage based on rim volume, rim area and disk
      size, as measured by Heidelberg retinal tomography (HRT III). Visual fields (VF)
      were assessed by Humphrey perimetry, and nerve fiber layer thickness was
      determined both by scanning laser polarimetry (GDxVCC) and spectral-domain
      optical coherence tomography (SD-OCT). Comparisons of all measured parameters
      were made between NTG and HTG groups. RESULTS: Based on HRT results, both NTG and
      HTG eyes displayed comparable structural damage to the ONH (NTG/HTG, mean: disk
      area, 2.30/2.31 mm(2), p = 0.942; rim area, 1.02/0.86 mm(2), p = 0.082; rim
      volume, 0.19/0.17 mm(3), p = 0.398). NTG eyes had significantly less VF damage
      than HTG eyes (NTG/HTG, mean deviation: -4.23/-12.12 dB, p = 0.002; pattern
      standard deviation: 5.39/8.23 dB, p = 0.022). The inferior nerve fiber layer of
      NTG patients was significantly thicker than that of HTG patients (NTG/HTG, mean:
      GDx inferior: 53.5/46.3 um, p = 0.046). SD-OCT revealed a significantly thicker
      nerve fiber in NTG compared with HTG patients in all quadrants (NTG/HTG, total
      mean: 72.72/58.45 um, p = 0.002). CONCLUSION: At comparable glaucomatous stages,
      nerve fiber loss was more advanced in HTG patients compared with NTG patients.

PMID- 24334968
TI  - First case of 18F-FACBC PET/CT-guided salvage retroperitoneal lymph node
      dissection for disease relapse after radical prostatectomy for prostate cancer
      and negative 11C-choline PET/CT: new imaging techniques may expand pioneering
      approaches.
AB  - We present the first case of salvage retroperitoneal lymph node dissection based
      on the results of (18)F-FACBC PET/CT performed for a prostate-specific antigen
      relapse after radical prostatectomy. The patients underwent (11)C-choline PET/CT,
      which turned out negative, while (18)F-FACBC PET/CT visualized two lymph node
      metastases confirmed at pathological examination. Preliminary clinical reports
      showed an improvement in the detection rate of 20-40% for (18)F-FACBC in
      comparison with (11)C-choline, rendering the (18)F-FACBC the potential
      radiotracer of the future. Salvage surgery for prostate cancer is a fascinating
      but controversial approach. New diagnostic tools may improve its potential by
      increasing the assessment and the selection of the patients.

PMID- 24334969
TI  - Erythrocyte n-3 polyunsaturated fatty acids and the risk of type 2 diabetes in
      Koreans: a case-control study.
AB  - BACKGROUND: There is inconsistent epidemiologic evidence for an association
      between tissue levels of n-3 polyunsaturated fatty acids (PUFAs) and the risk of
      type 2 diabetes. The purpose of the present study was to investigate whether
      erythrocyte levels of n-3 PUFAs are negatively associated with the risk of type 2
      diabetes and correlated with levels of glucose and HbA1c in Koreans. METHODS: A
      total of 130 patients with type 2 diabetes and 260 age- and sex-matched controls
      participated in this study. RESULTS: The risk of type 2 diabetes was negatively
      associated with erythrocyte levels of 22:5n3 and 22:6n3, which were negatively
      correlated with HbA1c levels after adjusting for age, sex and body mass index.
      Additionally, the risk of type 2 diabetes was negatively associated with
      erythrocyte levels of 18:0 and 20:4n6, but positively associated with erythrocyte
      levels of 16:0, 18:1n9, 18:3n3, 18:2n6, 18:3n6, n-6/n-3 PUFA ratio, 18:1t and
      18:2n6t, and Delta-6 desaturase (18:3n6/18:2n6) and Delta-9 desaturase
      (18:1n9/18:0) activities. CONCLUSIONS: The risk of type 2 diabetes was negatively
      associated with erythrocyte levels of n-3 PUFA, which were negatively correlated
      with HbA1c levels in Koreans, suggesting that n-3 PUFAs might reduce the risk of
      type 2 diabetes in Asians.

PMID- 24334970
TI  - The multitasking role of macrophages in Stanford type A acute aortic dissection.
AB  - OBJECTIVES: The aim of the study was to determine whether the release by
      macrophages of matrix metalloproteinase (MMP)-12 and vascular endothelial growth
      factor (VEGF) - leading to inflammation, matrix degradation and neoangiogenesis -
      represents an effective pathway that underlies aortic wall remodeling in Stanford
      type A acute aortic dissection (AAD). METHODS: Twenty-one consecutive patients
      with no genetic predisposition, with Stanford type A AAD were selected. In each
      patient, the levels of serum VEGF, MMP-12, serum interleukin (IL)-6, IL-8 and
      monocyte chemoattractant protein (MCP)-1 were evaluated using enzyme-linked
      immunosorbent assay. Ascending aortic specimens were collected for
      immunohistochemical identification of any presence of inflammatory infiltrate,
      VEGF and CD31 expression. RESULTS: A significant increase in serum VEGF (p =
      0.044), MMP-12 (p = 0.007), IL-6 (p = 0.0001), IL-8 (p = 0.0001) and MCP-1 (p =
      0.0001) levels was observed in the AAD group compared to the control group.
      Furthermore, all AAD samples were positive for VEGF in the tunica media and
      showed vessel growth and immune-inflammatory infiltrate. A large number of cases
      (62.79%) showed inflammation at the edge of the dissection and approximately half
      (51.42%) showed neovessels growing at the edge of the dissection. CONCLUSIONS:
      The results suggest that VEGF-mediated angiogenesis and matrix degradation play a
      role in AAD. Finally, we believe that MMP-12 should be considered a marker of
      AAD.

PMID- 24334971
TI  - Is there an appropriate cutoff age for sampling the endometrium in premenopausal
      bleeding?
AB  - AIM: To determine a cutoff age for endometrial evaluation in premenopausal
      abnormal uterine bleeding (AUB). METHODS: Histopathology reports of endometrial
      sampling performed due to AUB in women aged 50 years or less were reviewed
      retrospectively. Histopathological findings were categorized into three groups as
      follows: group 1: hyperplasia without atypia + hyperplasia with atypia +
      malignancy, group 2: hyperplasia with atypia + malignancy, and group 3:
      malignancy. RESULTS: Data from 2,516 patients were analyzed for this study.
      Overall, 13.5% of patients had endometrial hyperplasia without atypia, 1% of
      patients had hyperplasia with atypia and 0.6% of patients had malignant disease.
      Logistic regression revealed a significant difference in the odds ratios of group
      1 in the age ranges of 40-45 and 45-50 years compared with <40 years (p = 0.001
      and p = 0.01, respectively). There were no significant differences between the
      age groups for the odds ratio of group 2 and group 3. CONCLUSION: There is no
      cutoff age for sampling the endometrium in order to detect hyperplasia with
      atypia and cancer in premenopausal women with AUB. Therefore, the management of
      AUB should be tailored to each patient regardless of age, incorporating all risk
      factors for malignant disease.

PMID- 24334972
TI  - Metastatic plasmacytoid urothelial carcinoma: a case report and review of the
      literature.
AB  - Plasmacytoid urothelial carcinoma is a rare form of invasive urothelial carcinoma
      first described in 1991 by Sahin et al. [Acta Cytol 1991;35:277-280]. Since this
      original publication, over 70 cases of plasmacytoid urothelial carcinoma have
      been described. A small number of cytologic descriptions have been published,
      including cases involving cerebrospinal fluid cytology, bladder washings and
      urine cytology. To our knowledge, we describe the first fine needle aspiration of
      metastatic plasmacytoid urothelial carcinoma in a 75-year-old man who presented
      with a pathologic fracture of the L4 vertebral body. One of the diagnostic
      pitfalls in the cytologic evaluation of this rare malignancy is the positive
      staining with CD138. While CD138 is a marker for plasma cell differentiation, it
      is also positive in plasmacytoid urothelial carcinoma. In addition to recognizing
      the cytomorphologic details, a full immunohistochemical panel is helpful in
      properly characterizing this entity. A brief discussion of long-term prognosis
      and treatment benefit is provided.

PMID- 24334973
TI  - Treatment of aneurysmal subarachnoid haemorrhage in Germany: a nationwide
      analysis of the years 2005-2009.
AB  - BACKGROUND: The aim of this study was to provide population-based nationwide
      rates of the different treatment modalities of aneurysmal subarachnoid
      haemorrhage (aSAH). METHODS: German Diagnosis-Related Group data of the years
      2005-2009 were used to calculate hospitalisation rates for intracranial aneurysm
      with aSAH. This study includes over 83 million hospitalisations. RESULTS: We
      identified 15,768 hospitalisations with a diagnosis of aSAH. Throughout the
      observation period, the age-standardised rate for both sexes increased by 69%
      (95% confidence interval, CI 54-84) for coiling and 13% (95% CI 4-23) for
      clipping. The estimated annual percent change in the overall hospitalisation rate
      was 7.4% (95% CI 5.2-9.6). Age-standardised hospitalisation rates varied
      considerably by region. The estimated hospitalisation rate ratio of overall
      hospitalisation rates (East/West) was 0.86 (95% CI 0.80-0.91) for males and 0.81
      (95% CI 0.77-0.85) for females. After adjustment for age and co-morbidity, the
      hazard ratio (HR) for in-hospital mortality was higher for coiling than clipping
      (HR = 1.12, 95% CI 1.01-1.23). Patients who received coiling or clipping had
      ventricular shunt placement in 5.0 (n = 819) and 6.1% (n = 998), respectively.
      The estimated length of stay was 3.3 days (95% CI 2.56-4.05) shorter for coiling
      than clipping. CONCLUSIONS: We provide for the first time nationwide,
      representative hospitalisation rates for the treatment of aSAH. Our results
      indicate a change in the practice pattern for Germany during the observation
      period. We observed a gradual increase in overall hospitalisation rates for aSAH.

PMID- 24334974
TI  - Atazanavir-induced urine crystals demonstrated by infrared spectroscopic
      analysis.
AB  - Atazanavir sulfate, an azapeptide inhibitor of HIV protease, has been associated
      with urolithiasis. A 60-year-old man with atazanavir-induced urinary sediment
      crystals verified by infrared spectroscopic analysis is described. He had been
      receiving highly active antiretroviral therapy (HAART) for HIV infection and also
      had a history of urinary lithiasis and been undergoing urinalysis once every
      month. Needle-shaped crystals were seen in his urine sediment and infrared
      spectroscopic analysis revealed that these were atazanavir crystals. Because the
      presence of the crystals in urine do not always reveal an abnormality in the
      urinary test strip analysis, the urinary sediment needed to be observed
      microscopically in order to prevent future urolithiasis and renal failure in this
      HIV patient receiving atazanavir.

PMID- 24334977
TI  - On-line sample preconcentration by large-volume sample stacking with an
      electroosmotic flow pump (LVSEP) in microscale electrophoresis.
AB  - This review highlights on-line sample preconcentration by large-volume sample
      stacking with an electroosmotic flow pump (LVSEP) in microscale electrophoresis.
      LVSEP requires only a hydrodynamic sample injection into the whole
      capillary/microchannel and a constant voltage application, i.e., without polarity
      switching, providing an efficient sensitivity enhancement with a relatively easy
      experimental procedure without loss of the separation efficiencies. Recent
      developments and applications of LVSEP are briefly reviewed from the first LVSEP
      study in 1999 with categorization on the basis of separation modes, including
      zone electrophoresis, cyclodextrin- and affinity-based separation modes and non
      aqueous capillary electrophoresis. 

PMID- 24334976
TI  - Recent developments in liquid chromatography and capillary electrophoresis for
      the analysis of glycoprotein glycans.
AB  - Oligosaccharides attached to proteins are very challenging analytical targets
      because of their wide variety and complexity. Reliable analytical methods for the
      quantitative profiling of glycoprotein glycans is essential for investigating
      their functions in biological systems, and for use in the production of
      recombinant glycoproteinaceous pharmaceuticals. The most reliable and
      straightforward method to view glycan compositions is fluorescent labeling,
      followed by liquid chromatography or capillary electrophoresis. This article
      briefly summarizes the methods used for releasing glycans from glycoproteins and
      the purification with various solid phases, labeling, and separation by liquid
      chromatography and capillary electrophoresis of the released glycans. 

PMID- 24334975
TI  - Maternal leptin predicts adiposity of the neonate.
AB  - BACKGROUND: Increased adiposity at birth may identify infants at high risk of
      developing obesity. Maternal obesity and hyperglycemia in pregnancy are
      associated with increased neonatal adiposity; however, features of maternal
      obesity that contribute to increased neonatal adiposity need further study. AIMS:
      To measure adiposity in neonates of obese and normal-weight women without
      gestational diabetes to test the hypothesis that obese women have neonates with
      increased adiposity compared to neonates of normal-weight women. METHODS: Sixty
      one pregnant women, with a normal or obese BMI, and their neonates participated
      in this cross-sectional study at an academic medical center. Neonatal adiposity,
      expressed as percent body fat (fat mass/body mass), was measured by air
      displacement plethysmography and cord blood was assayed for biomarkers. RESULTS:
      Adiposity in neonates of obese and normal-weight mothers did not differ.
      Stratifying mothers by leptin level showed that neonates born to mothers with
      higher leptin had significantly higher adiposity (13.2 vs. 11.1%, p = 0.035). In
      the entire cohort, adiposity positively correlated with cord blood leptin (r =
      0.48, p < 0.001) and adiponectin (r = 0.27, p = 0.04) levels. CONCLUSION: Obesity
      in normoglycemic pregnant women was not associated with increased neonatal
      adiposity. High maternal leptin levels identified neonates with increased
      adiposity.

PMID- 24334978
TI  - Development of the atmospheric plasma soft-ablation method (APSA) for elemental
      analysis of materials on heat-sensitive substrates.
AB  - To achieve a highly sensitive and prompt elemental analysis of materials on heat
      sensitive substrates, like living tissues, the atmospheric plasma soft-ablation
      method (APSA) was developed. The damage-free plasma, which has room temperature
      and no risk of electrical shock, was used as a sampling medium for materials, and
      the sampled materials were introduced to inductively coupled plasma mass
      spectrometer (ICP-MS). By using APSA, a mass signal of molybdenum, using a thin
      molybdenum-grease layer, was successfully obtained without damaging the subjacent
      glass substrate. The use of a hydrogen admixture to generate the plasma was
      examined in order to achieve more effective sampling by utilizing chemical
      reactions between radicals in the plasma and the sample material. As a result,
      the sensitivity of all measured elements contained in tablet supplements
      increased by up to 20 times upon the addition of 1% hydrogen, even though the
      plasma-gas temperature did not change significantly. 

PMID- 24334979
TI  - Development of injection gas heating system for introducing large droplets to
      inductively coupled plasma.
AB  - We developed an injection gas heating system for introducing large droplets,
      because we want to effectively to measure elements in a single cell. This system
      was applied to ICP-atomic emission spectrometry (ICP-AES), to evaluate it
      performance. To evaluate the effect of the emission intensity, the emission
      intensity of Ca(II) increased to a maximum of tenfold at 147 degrees C and the
      peak was shifted upstream of the plasma. To investigate in detail the effect of
      an injection gas heating system, we studied different conditions of the injection
      gas temperature and droplet volume. When the injection gas temperature was 89
      degrees C, smaller droplets were easily ionized. At 147 degrees C, the emission
      intensity ratio and the absolute amount of the sample including the droplet
      exhibited close agreement. These results show the advantages of the injection gas
      heating system for large droplet introduction, and the sufficient reduction in
      the solvent load. The solvent load could be reduced by heating to 147 degrees C
      using the system. 

PMID- 24334980
TI  - Determination of diphenylarsinic acid, phenylarsonic acid and inorganic arsenic
      in drinking water by graphite-furnace atomic-absorption spectrometry after
      simultaneous separation and preconcentration with solid-phase extraction disks.
AB  - A simple method of graphite-furnace atomic-absorption spectrometry (GFAAS) after
      solid-phase extraction (SPE) was developed for the determination of
      diphenylarsinic acid (DPAA), phenylarsonic acid (PAA), and inorganic arsenic
      (iAs) in drinking water. This method involves the simultaneous collection of
      DPAA, PAA, and iAs using three stacked SPE disks, i.e., an Empore SDB-XD disk
      (the upper layer), an activated carbon disk (the middle layer), and a Cation-SR
      disk loaded with Zr and Ca (ZrCa-CED; the lower layer). A 200-mL aqueous sample
      was adjusted to pH 3 with nitric acid and passed through the SPE disks at a flow
      rate of 15 mL min(-1), to concentrate DPAA on the SDB-XD disk, PAA on the
      activated carbon disk, and iAs on the ZrCa-CED. The As compounds were eluted from
      the disks with 10 mL of ethanol containing 0.5 mol L(-1) ammonia solution for
      DPAA, 20 mL of 1 mol L(-1) ammonia solution for PAA, and 20 mL of 6 mol L(-1)
      hydrochloric acid for iAs. The eluates of DPAA, PAA, and iAs were diluted to 20,
      25, and 25 mL, respectively, with deionized water, and then analyzed by GFAAS.
      The detection limits of As (three-times the standard deviation (n = 3) of the
      blank values) were 0.13 and 0.16 MUg L(-1) at enrichment factors of 10 and 8,
      respectively, using a 200-mL water sample. Spike tests with 2 MUg (10 MUg L(-1))
      of DPAA, PAA, and iAs in 200 mL of tap water and bottled drinking water showed
      good recoveries (96.1-103.8%).

PMID- 24334981
TI  - Characteristics of the calibration curves of copper for the rapid sorting of
      steel scrap by means of laser-induced breakdown spectroscopy under ambient air
      atmospheres.
AB  - For the rapid and precise sorting of steel scrap with relatively high contents of
      copper, laser-induced breakdown spectroscopy (LIBS) is a promising method. It has
      several advantages such that it can work under ambient air atmospheres, and
      specimens can be tested without any pretreatment, such as acid digestion,
      polishing of the surface of the specimens, etc. For the application of LIBS for
      actual steel scrap, we obtained emission spectra by an LIBS system, which was
      mainly comprised of an Nd:YAG laser, an Echelle-type spectrometer, and an ICCD
      detector. The standard reference materials (SRMs) of JISF FXS 350-352, which are
      Fe-Cu binary alloy and have certified concentrations of copper, were employed for
      making calibration lines. Considering spectral interferences from the emission
      lines of the iron matrix in the alloys, Cu I lines having wavelengths of 324.754
      and 327.396 nm could be chosen. In five replicate measurements of each SRM,
      shorter delay times after laser irradiation and longer gate widths for detecting
      the transient emission signal are suggested to be the optimal experiment
      parameters. In the determination process, utilizing the calibration line from Cu
      I 327.396 nm was better because of less spectral interference. By using 200
      pulsed laser shots for the measurement sequence, a limit of detection of 0.004 Cu
      at% could be obtained. 

PMID- 24334982
TI  - Ratiometric fluorescence recognition for pyrophosphate on the basis of
      terpyridine derivative.
AB  - Diphosphate (pyrophosphate, PPi) is vital for organisms, and therefore its
      detection is of special importance. In this paper, one cadmium complex of
      terpyridine (tpy) derivative, 4'-(aminomethylphenyl)-2,2':6',2"-terpyridine
      (aptpy), has been reported for the ratiometric fluorescence recognition of PPi.
      When added with cadmium, the emission of aptpy at 358 nm was greatly enhanced and
      red shifted to 397 nm due to the complexation-induced ICT process, which then
      blue shifted to 349 nm upon the further addition of PPi. Based on the different
      response of dual fluorescence emissions at 349 and 397 nm, a ratiometric
      fluorescence method could be successfully established for the fluorescence
      recognition of PPi. With that, PPi could be successfully discriminated from other
      structurally similar anions, including nucleotide triphosphates.

PMID- 24334983
TI  - A highly selective fluorescent probe for quantitative detection of hydrogen
      sulfide.
AB  - We designed and synthesized a highly selective and sensitive fluorescent probe
      for hydrogen sulfide (H2S) based on the one step nucleophilic addition reaction
      between H2S and electron-poor C=C double bond. Our proposed probe displayed high
      selectivity for H2S over other analytes including cysteine (Cys) and glutathione
      (GSH), which might be because the steric hindrance of H2S is less than other
      thiols. Additionally, a linear relationship between fluorescence intensity and
      the concentrations of Na2S (0-450 MUM) was obtained in an aqueous buffer solution
      (pH 7.4, 20 mM PBS). Particularly, we found that the adoption of the acetyl
      benzimidazole derivative as a recognition receptor to distinguish H2S from other
      thiols and analytes provides a promising methodology for the design of
      fluorescent probes for the determination of H2S.

PMID- 24334984
TI  - Simultaneous quantitation of alpha-ketoglutaric acid and 5-hydroxymethylfurfural
      in plasma by HPLC with UV and fluorescence detection.
AB  - Alpha-ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) are currently being
      investigated in clinical trials as an approach in targeted cancer therapy. Hence,
      a method for the simultaneous determination of KG and HMF in plasma has been
      developed. Due to the strongly discriminative chemical properties of KG and HMF,
      SPE purification is performed using an ion-exchange cartridge to separate KG, and
      a hydrophobic polymeric cartridge to separate HMF. The cartridges are connected
      together for several steps, thus resulting in a quicker approach for the
      purification of plasma samples. The derivatization step is based on the reaction
      of the carbonyl groups of KG and HMF with dansylhydrazine (DNSH) catalyzed by
      trifluoroacetic acid. The formed derivatives could be separated by reversed-phase
      LC on a C8-column, and analyzed by UV and fluorescence detection in a single run
      using a gradient program. The obtained results show good reproducibility,
      specificity, and detection limits down to the low picomole range. 

PMID- 24334985
TI  - Simultaneous determination of azoles antifungal drugs in chicken tissues by ultra
      performance liquid chromatography tandem mass spectrometry.
AB  - An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      method was established for the simultaneous determination of residues of
      enilconazole, parconazole, thiabendazole and its metabolite, 5
      hydroxythiabendazole, in chicken tissues including liver, muscle and egg.
      Homogenized samples were extracted by acetonitrile, concentrated and purified by
      an Oasis MCX solid-phase extraction cartridge. Analysis of the target drugs was
      performed by liquid chromatography with an UPLCTM BEH C18 column, coupled with a
      tandem mass spectrometry (UPLC-MS/MS) operating in the positive multiple-reaction
      mode (MRM). Good linearity was obtained at concentrations of 0.10-100 MUg kg(-1).
      The average recoveries of the analytes in chicken liver, muscle and egg at six
      fortification levels were in the range 93.6-119.5% with acceptable coefficients
      of variation (<14.8%). The detection capability (CCbeta) of the analytes upon the
      method ranged from 0.05 to 138.1 MUg kg(-1). This method was successfully applied
      in screening and confirming of target drugs in tens of real samples.

PMID- 24334986
TI  - A new method for determining the absorbed dose in a radiation field by using a
      thiamine hydrochloride aqueous solution.
AB  - This research investigated the ionizing radiation effect on thiamine
      hydrochloride (TH) and its usability as an irradiation dosimeter. The fundamental
      principle is to determine the concentration variations of TH solutions with high
      performance liquid chromatography (HPLC) after exposing to gamma-rays. The
      decreasing peak area of TH in the HPLC chromatogram forms a linear relationship
      with the rising radiation dose. We investigated the characteristics and suitable
      application range of the TH as a new radiation dosimeter. The influence factors
      and mechanism of the reaction induced by radiation were also discussed. According
      to the correlation between the concentration and the radiation dose, 0.3 g/L of a
      TH solution is suitable for the 0.1-10 kGy dose range, and 2 g/L is appropriate
      for 0.1-20 kGy. The easy availability and the simple, but stable, chemical
      structure of thiamine makes it a potential candidate for radiation dose research.
      Also, the preparation proceeding for sampling is easy, and the result can be
      automatic monitored by liquid chromatography.

PMID- 24334987
TI  - Guanine-decorated graphene nanostructures for sensitive monitoring of neuron
      specific enolase based on an enzyme-free electrocatalytic reaction.
AB  - A new and enzyme-free electrochemical immunoassay protocol was developed for the
      sensitive electronic monitoring of neuron-specific enolase (NSE) on a monoclonal
      mouse anti-human NSE antibody (mAb)-modified glassy carbon electrode, using
      guanine-decorated graphene nanostructures (GGN) as nanotags. To construct such an
      enzyme-free immunoassay format, guanine and polyclonal rabbit anti-human NSE
      antibody (pAb) were co-immobilized on the graphene nanostructures through the
      carbodiimide coupling. Based on a sandwich-type immunoassay mode, the assay was
      carried out in 0.1 M pH 7.4 PBS containing 5 MUM Ru(bpy)3(2+) through the
      catalytic oxidation of Ru(bpy)3(2+) toward the guanine on the GGN. The presence
      of graphene nanostructures increased the immobilized amount of guanine, thus
      amplifying a detectable electronic signal. The covalent conjugation of guanine
      and pAb on the GGN resulted in a good repeatability and intermediate
      reproducibility down to 9.5%. Under optimal conditions, the dynamic concentration
      range of the developed immunoassay spanned from 0.005 to 80 ng mL(-1) NSE with a
      detection limit of 1.0 pg mL(-1) at the 3S(blank) level. In addition, the
      methodology was evaluated by assaying the spiking serum samples, and the relative
      standard deviation (RSD) between the electrochemical immunoassay and a
      commercialized enzyme-linked immunosorbent assay (ELISA) were 2.8-7.0%.

PMID- 24334988
TI  - Development of electrochemical microbiochip for the biological diagnosis of
      Neisseria gonorrhoeae.
AB  - A sexually transmitted disease is an illness that has a high probability of
      transmission between humans or animals who have sexual contact. Our research is
      based on the development of a microbiochip for Neisseria gonorrhoeae (N.G.). In
      our study, we have employed fusion technology between microarray technology and a
      microfluidic system for quantitative analysis of N.G. A great deal of attention
      has been focused on electrochemical detection by using a DNA probe, which is a
      specific DNA sequence and binds to a target biomolecule, because of high
      affinity, ease of usage, and fast measurement. The microbiochip consisted of two
      electrode systems and microchannel based PDMS. Our detection principles use
      electrochemical detection. Consequently, our microbiochip detected 5 ng/mL of
      N.G. and the correlation rate was over 0.95. We can produce a microbiochip, which
      could bind to a DNA probe and detect sample of interest. We expect that our
      electrobiochemical chip will be used for the development of a portable device. 

PMID- 24334989
TI  - Determination of the carbon, hydrogen and nitrogen contents of alanine and their
      uncertainties using the certified reference material L-alanine (NMIJ CRM 6011-a).
AB  - The carbon, hydrogen, and nitrogen (CHN) contents of alanine and their
      uncertainties were estimated using a CHN analyzer and the certified reference
      material (CRM) L-alanine. The CHN contents and their uncertainties, as measured
      using the single-point calibration method, were 40.36 +/- 0.20% for C, 7.86 +/-
      0.13% for H, and 15.66 +/- 0.09% for N; the results obtained using the bracket
      calibration method were also comparable. The method described in this study is
      reasonable, convenient, and meets the general requirement of having uncertainties
      <= 0.4%. 

PMID- 24334990
TI  - Evaluation of UV-fs-LA-MC-ICP-MS for precise in situ copper isotopic
      microanalysis of cubanite.
AB  - We evaluated the capabilities of an in situ method for measuring copper isotopes
      of cubanite using UV-fs-LA-MC-ICP-MS. A comparison of the UV-fs laser results
      with those obtained from the NIR-fs laser system shows that there is obviously an
      improvement in the precision (<0.100/00, 2SE) when using the UV-fs laser. In both
      wavelength modes, matrix-matched standards are required for reliable in situ
      copper isotope analysis of cubanite. This method was applied to determinations
      for copper isotopes of minute cubanite grains in a skarn ore. Copper isotopic
      ratios of cubanite grains near a weathered surface of the sample are lower than
      those of intact cubanite grains within the sample, suggesting that selective
      leaching of heavier copper isotope in primary minerals occurred during
      weathering. 

PMID- 24334991
TI  - Determination of carbonyl compounds generated from the E-cigarette using coupled
      silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine,
      followed by high-performance liquid chromatography.
AB  - Carbonyl compounds in E-cigarette smoke mist were measured using coupled silica
      cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine, followed
      by high-performance liquid chromatography. A total of 363 E-cigarettes (13
      brands) were examined. Four of the 13 E-cigarette brands did not generate any
      carbonyl compounds, while the other nine E-cigarette brands generated various
      carbonyl compounds. However, the carbonyl concentrations of the E-cigarette
      products did not show typical distributions, and the mean values were largely
      different from the median values. It was elucidated that E-cigarettes
      incidentally generate high concentrations of carbonyl compounds. 

PMID- 24334992
TI  - In situ quantification of ammonium sulfate in single aerosol droplets by means of
      laser trapping and Raman spectroscopy.
AB  - Noncontact levitation in air of single micrometer-sized water droplets containing
      ammonium sulfate was successful by a laser trapping technique. The trapping laser
      beam was also used simultaneously as an excitation light source for the Raman
      spectroscopy of trapped droplets. Raman scattering of the symmetric stretching
      vibration of the SO4(2-) anion and the OH stretching vibrations of H2O were
      observed at 980 and 3420 cm(-1), respectively. The intensity ratio of these two
      Raman peaks was linearly proportional to the ammonium sulfate concentration in
      water. Therefore, the in situ quantification of ammonium sulfate in single
      aerosol droplets was achieved by means of laser trapping and Raman spectroscopy.
      To the best of our knowledge, this study is the first experimental observation of
      the independence of ammonium sulfate concentrations of aerosol water droplets to
      those of the mother solutions under constant relative humidity conditions. 

PMID- 24334996
TI  - Hepatic injury correlates with apoptosis, regeneration, and nitric oxide synthase
      expression in canine chronic liver disease.
AB  - Assessment of the clinical severity, pathogenesis, and prognosis of canine
      chronic liver disease poses significant challenges to clinicians and
      pathologists, relating in part to a lack of standardized terminology and
      assessment methods and also to a lack of understanding of the pathogenesis of
      chronic liver disease in the dog. This study graded the severity of
      necroinflammatory activity in chronic liver disease in dogs using a modification
      of Ishak's grading scheme for human chronic liver disease and examined the
      association of grade score with hepatocellular apoptosis, regeneration, nitric
      oxide synthase isoform expression, copper and iron accumulation, and indicators
      of oxidative stress. Formalin-fixed, paraffin-embedded hematoxylin and eosin (HE)
      stained liver biopsies from 45 dogs with chronic liver disease and 55 healthy
      control dogs were graded for various morphologic components of liver injury and
      response. The cumulative score for grade of necroinflammatory activity was
      strongly and significantly correlated with immunoreactive labels for
      hepatocellular proliferation (Ki-67); apoptosis (cleaved caspase-3); inducible
      nitric oxide synthase (iNOS) in lobular, portal, and septal stromal cells;
      endothelial nitric oxide synthase (eNOS) in hepatocytes and lobular, portal, and
      septal stromal cells; and total stainable hepatic iron. A weaker significant
      correlation was found between grade and accumulation of hepatocellular copper. No
      significant correlation was found between grade and immunoreactivity for
      malondialdehyde-protein adducts. These results document a method for grading of
      the severity of necroinflammatory disease in canine liver biopsies and show an
      association with increased iNOS and eNOS expression. 

PMID- 24334997
TI  - PAX2 and PAX8: useful markers for metastatic effusions.
AB  - OBJECTIVE: It was the aim of this study to determine the utility of PAX2 and PAX8
      in cytology effusions with metastatic tumor. STUDY DESIGN: PAX2 and PAX8
      immunohistochemical staining was performed on cell blocks of 89 pleural,
      pericardial and peritoneal effusions with benign diagnoses (18 cases), or
      secondary to renal cell carcinoma (RCC; 9 cases), mullerian carcinoma (21 cases)
      or non-mullerian carcinoma (41 cases). RESULTS: PAX2 stained 0% (0/18) of
      controls, 100% (8/8) of RCCs, 35% (7/20) of mullerian carcinomas, and 2% (1/41)
      of non-mullerian carcinomas. PAX8 stained 6% (1/18) of control cases, 100% (9/9)
      of RCC cases, 100% (20/20) of mullerian carcinomas, and 5% (2/41) of non
      mullerian carcinomas. PAX2 was 35% sensitive and 95% specific for mullerian
      carcinoma and 100% sensitive and 95% specific for RCC. PAX8 was 100% sensitive
      and 95% specific for mullerian carcinoma and 100% sensitive and 95% specific for
      RCC. CONCLUSIONS: PAX8 is more sensitive than PAX2 for metastatic effusions from
      mullerian carcinomas (100 vs. 35%), while also having a higher intensity of
      staining than PAX2. However, PAX2 and PAX8 are both highly sensitive and specific
      for RCCs. PAX2 and PAX8 are valuable diagnostic markers for metastatic mullerian
      carcinomas and RCCs in effusion cytology. PAX8 is superior for carcinomas of
      mullerian origin.

PMID- 24334995
TI  - Mycobacterium microti tuberculosis in its maintenance host, the field vole
      (Microtus agrestis): characterization of the disease and possible routes of
      transmission.
AB  - The field vole (Microtus agrestis) is a known maintenance host of Mycobacterium
      microti. Previous studies have shown that infected animals develop tuberculosis.
      However, the disease is also known in cats and is sporadically reported from
      humans and other mammalian species. We examined trapped field voles from an
      endemic area, using a range of diagnostic approaches. These confirmed that a
      combination of gross and histological examination with culture is most
      appropriate to identify the true prevalence of the disease, which was shown to be
      more than 13% at times when older animals that have previously been shown to be
      more likely to develop the disease dominate the population. The thorough
      pathological examination of diseased animals showed that voles generally develop
      systemic disease with most frequent involvement of spleen and liver, followed by
      skin, lymph nodes, and lungs. The morphology of the lesions was consistent with
      active disease, and their distribution suggested skin wounds or oral and/or
      aerogenic infection as the main portal of entry. The demonstration of
      mycobacteria in open skin lesions, airways, and salivary glands indicated
      bacterial shedding from the skin and with sputum and saliva. This suggests not
      only the environment but also direct contact and devouring as likely sources of
      infection. 

PMID- 24334998
TI  - Monotherapy with intravenous vinflunine in patients with advanced or metastatic
      urothelial cancer after failure of a platinum-containing regimen: a retrospective
      analysis of German routine data.
AB  - OBJECTIVE: The objective of this retrospective study was to investigate the
      efficacy and safety of vinflunine monotherapy and the utility of second-line
      prognostic factors in patients with advanced or metastatic urothelial cancer
      relapsing/progressing during or after a prior platinum-containing regimen under
      daily routine clinical conditions in Germany. METHODS: The selection was based on
      the marketing authorization indication and recommendations as well as on the
      evaluation of second-line prognostic factors issued from prior pivotal trials.
      RESULTS: Eight centers across Germany provided a total of 21 patient records.
      Demographic and clinical characteristics were similar to the data previously
      reported in pivotal trials. Complete and partial response to vinflunine treatment
      was observed in 1 (4.8%) and 3 (14.3%) patients, respectively, resulting in an
      overall response rate of 19.1%. The disease control rate reached 47.7%. The
      median progression-free survival amounted to 4.4 months (95% CI 2.6-6.6), with a
      median overall survival of 6.2 months (95% CI 3.9-10.7). The observed toxicity
      profile was manageable and consistent with prior clinical trials: leukopenia
      (33.3%), neutropenia (9.5%), anemia (9.5%) and hyperglycemia (4.8%). The reported
      satisfaction rate with the treatment was 90.5 and 61.9% among patients and
      physicians, respectively. CONCLUSIONS: This retrospective study confirms that the
      clinical outcomes obtained from routine medical practice in Germany with
      vinflunine in the treatment of advanced/metastatic urothelial cancer are in line
      with the data observed in prior clinical trials.

PMID- 24334999
TI  - Combination of corpus callosotomy and vagus nerve stimulation in the treatment of
      refractory epilepsy.
AB  - BACKGROUND: Palliative techniques such as partial corpus callosotomy (CC) and
      vagus nerve stimulation (VNS) may be effective for adequate control of seizures
      in pharmacoresistant patients who are not candidates for resective surgery.
      OBJECTIVE: The objective of this study was to analyze the efficacy of the
      combination of these two techniques in patients where the first surgery had not
      achieved adequate control. MATERIALS AND METHODS: This is a retrospective review
      of 6 patients with refractory epilepsy in which both types of surgery were
      performed, CC and VNS. We analyzed variables such as age, sex, age at onset of
      epilepsy, seizure types, electroencephalogram and magnetic resonance imaging
      results, and number of pre- and postoperative seizures. RESULTS: Three patients
      first underwent VNS and then CC, and 3 patients were treated in reverse order.
      All patients had some improvement after the first surgery, but they continued to
      experience persistent falls, so a second palliative technique was used. The mean
      improvement after both surgeries was 89% (90% in patients first receiving CC and
      87% in patients who first underwent VNS). CONCLUSIONS: In adequately studied
      patients who are not optimal candidates for resective surgery, palliative surgery
      is a choice. The combination of VNS and CC shows good results in our series,
      although the right order to perform both procedures has not been defined. These
      results should be confirmed in a larger group of patients.

PMID- 24335000
TI  - Association between adiponectin receptor 1 gene polymorphism and insulin
      resistance in Chinese patients with polycystic ovary syndrome.
AB  - BACKGROUND/AIMS: Adiponectin receptor 1 (ADIPOR1) is an identified receptor for
      adiponectin, an adipocytokine with anti-inflammatory and insulin-sensitizing
      properties. The ADIPOR1 gene is a potential candidate gene in polycystic ovary
      syndrome (PCOS). The aim of this study is to assess the association between
      single-nucleotide polymorphism (SNP) rs1539355 in the ADIPOR1 gene and PCOS in
      Chinese women. METHODS: 302 patients with PCOS and 312 healthy controls were
      included in this study. The ADIPOR1 genotype distribution was detected using the
      polymerase chain reaction melting temperature shift method. RESULTS: The
      genotypic distributions of SNP rs1539355 did not differ in patients with PCOS
      compared to controls. However, the frequency of the G allele in the PCOS group
      was significantly higher than that in the control group (p = 0.037). Patients
      with the AG or GG genotype had a higher homeostasis model assessment for insulin
      resistance (HOMA-IR) (p < 0.05) compared to patients with the AA genotype. The
      fasting insulin levels in subjects with the GG genotype were significantly higher
      than those in patients with the AA genotype (p < 0.05). CONCLUSION: SNP rs1539355
      in the ADIPOR1 gene is associated with insulin resistance in Chinese PCOS
      patients.

PMID- 24335001
TI  - Editorial.

PMID- 24335004
TI  - Treating percutaneous coronary intervention-related myocardial injury with
      metformin.

PMID- 24335005
TI  - Physical assessment and anthropometric measures for use in clinical research
      conducted in critically ill patient populations: an analytic observational study.
AB  - BACKGROUND: Accurate assessment of nutrition status is essential in identifying
      subpopulations of critically ill patients who are malnourished and at higher
      mortality risk. The aim of this analytic observational study was to assess the
      performance of physical assessment and anthropometric measures commonly used in
      clinical research. METHODS: A prospective study was undertaken in 31 intensive
      care units (ICUs) with a focus on patients with short-term contraindications to
      enteral nutrition. Within 24 hours of admission to the ICU, the following
      measures were collected: the Subjective Global Assessment components measuring
      subcutaneous fat loss and muscle wasting, height, weight, mid-upper-arm
      circumference, and triceps skinfold thickness (TSF). Mid-arm muscle circumference
      and body mass index (BMI) were calculated. BMI was assessed as a continuous
      variable and categorized according to the World Health Organization (WHO)
      categories. The primary outcome was hospital discharge mortality. RESULTS: In
      total, 1363 patients were enrolled. BMI, analyzed according to WHO categories (P
      = .09), and TSF (P = .32) failed to demonstrate statistically significant
      predictive ability. TSF failed to demonstrate statistically significant clinical
      utility (area under the receiver operating characteristic curve, 0.52; 95%
      confidence interval, 0.48-0.56). All other individual measures demonstrated
      statistically significant predictive ability and statistically significant
      clinical utility. CONCLUSIONS: On the basis of the results of our ICU cohort, we
      recommend caution when using BMI categorized according to WHO definitions. We
      cannot recommend collection of TSF. More research is required to understand
      reliability, performance, and use before our results are able to be generalized
      to other ICU populations.

PMID- 24335006
TI  - Hospital-based study in the context of subarachnoid haemorrhage practice and
      literature: factors to consider.

PMID- 24335007
TI  - Prednisolone markedly reduced serum IgG4 levels along with the improvement of
      pituitary mass and anterior pituitary function in a patient with IgG4-related
      infundibulo-hypophysitis.
AB  - In 2011 a 76 year-old man with a medical history of diabetes, hypertension and
      autoimmune pancreatitis was admitted to our hospital because of anorexia, general
      malaise and repeated hypoglycemia. When he was 72 years old, he suffered from
      pancreatitis, and pancreas head tumor was operated. IgG4-related pancreatitis was
      diagnosed histopathologically. On admission anterior pituitary function test
      revealed impaired response of ACTH and cortisol to CRH, and no response of GH,
      TSH and gonadotropin to GHRH, TRH and LHRH, respectively. Baseline PRL level was
      elevated. Serum IgG and IgG4 levels were markedly elevated. Pituitary MRI showed
      significant enlargement of pituitary gland and stalk. Chest CT suggested IgG4
      related lung disease. IgG4-related infundibulo-hypophysitis was diagnosed based
      on the above mentioned past history and results of present examinations. Twenty
      mg of hydrocortisone, followed by 20 mg of prednisolone (PSL) and 25 MUg of
      levothyroxine markedly reduced serum IgG4 levels and ameliorated the symptom, the
      size of pituitary and stalk, and anterior pituitary function (TSH, GH and
      gonadotropin), although diabetes insipidus became apparent due to glucocorticoid
      administration. This is a typical case of IgG4-related hypophysitis in which PSL
      causes marked improvement of pituitary mass and pituitary function along with the
      reduction of serum IgG4 levels. 

PMID- 24335008
TI  - Strategy of operative treatment of hyperparathyroidism using US scan and (99m)Tc
      MIBI SPECT/CT.
AB  - We evaluated the efficacy of technetium-sestamibi ((99m) Tc-MIBI) SPECT/CT for
      planning parathyroidectomy in cases with primary hyperparathyroidism (pHPT),
      comparing with planar scintigraphy and ultrasound (US), in an aim to establish
      the proper surgical strategy according to the preoperative imaging studies. A
      retrospective review of consecutive 75 pHPT patients who had been operated on was
      conducted. The results of preoperative imaging modalities and the operative
      finding were analyzed. Seven cases were found to have multiple hyperplastic
      glands, and no responsible gland was found in three cases. Four cases underwent
      only US scan for preoperative imaging. Remaining 61 cases were found to have
      single adenoma, and were included in the evaluation of localization imaging. US
      scan, (99m) Tc-MIBI planar scan and (99m) Tc-MIBI SPECT/CT showed accurate
      localization in 77.0% (47/61), 75.4% (46/61) and 88.5% (46/52) of the evaluable
      cases, respectively. US and (99m) Tc-MIBI planar scan demonstrated consistent
      result in 42 cases (68.9%), and those cases showed accurate localization in 90.5%
      (38/42). When both US and (99m) Tc-MIBI SPECT/CT was consistent, all 37 lesions
      had been correctly indicated. No clinico-pathological features were suggested to
      influence in demonstrating the localization, other than only (99m) Tc-MIBI
      SPECT/CT exhibited 100% sensitivity in ectopic glands. Combination of US and
      (99m) Tc-MIBI SPECT/CT certainly contributes to the planning of minimally
      invasive operation in cases with pHPT by indicating correct localization of
      single adenoma. 

PMID- 24335009
TI  - Disruption of transforming growth factor-beta signaling in thyroid follicular
      epithelial cells or intrathyroidal fibroblasts does not promote thyroid
      carcinogenesis.
AB  - Transforming growth factor beta (TGF-beta) members, pleiotropic cytokines, play a
      critical role for carcinogenesis generally as a tumor suppressor in the early
      cancer development, but as a tumor promoter in the late stage of cancer
      progression. The present study was designed to clarify the role for TGF-beta
      signaling in early thyroid carcinogenesis using the conditional
      Tgfbr2(floxE2/floxE2) knock-in mice, having 2 loxP sites at introns 1 and 2 of
      Tgfb2r gene. When these mice were crossed with thyroid peroxidase (TPO)-Cre or
      fibroblast-specific protein-1 (FSP1)-Cre, the resultant mice, Tgfbr2(tpoKO) and
      Tgfbr2(fspKO), lost TGF-beta II receptor expression (thereby TGF-beta signaling)
      specifically in the thyroid follicular epithelial cells or fibroblasts,
      respectively. The thyroid morphology was monitored up to 52 weeks in these mice,
      showing no tumor development, except one Tgfbr2(tpoKO) mouse developing
      follicular adenoma like-lesion. Our data suggest that TGF-beta signaling in
      mesenchymal or follicular epithelial cells of the thyroid does not appear to
      function as a tumor suppressive barrier at the early stage of thyroid
      carcinogenesis. 

PMID- 24335010
TI  - Superior mesenteric artery syndrome and intra-abdominal compartment syndrome in
      systemic lupus erythematosus.
AB  - Gastrointestinal manifestations of systemic lupus erythematosus (SLE) are common,
      occurring in about 50% of cases. They are usually mild, in the form of mouth
      ulcers, nausea, heartburn and mild abdominal pain, but they can be severe in
      cases of gastrointestinal vasculitis. In this report we describe an unusual
      combination of SLE complications, namely superior mesenteric artery syndrome
      (SMAS) and reversible acute obstructive renal failure. This was attributed to
      raised intra-abdominal pressure and hence intra-abdominal compartment syndrome
      (IACS) following weight loss secondary to an acute presentation of SLE with
      gastrointestinal vasculitis. 

PMID- 24335011
TI  - Orbital myositis associated with discoid lupus erythematosus.

PMID- 24335012
TI  - The needs of persons with lupus and health care providers: a qualitative study
      aimed toward the development of the Lupus Interactive NavigatorTM.
AB  - OBJECTIVE: Systemic lupus erythematosus is an inflammatory autoimmune disease
      associated with high morbidity and unacceptable mortality. A major challenge for
      persons with lupus is coping with their illness and complex care. Our objective
      was to identify the informational and resource needs of persons with lupus,
      rheumatologists, and allied health professionals treating lupus. Our findings
      will be applied toward the development of an innovative web-based technology, the
      Lupus Interactive Navigator (LINTM), to facilitate and support engagement and
      self-management for persons with lupus. METHODS: Eight focus groups were
      conducted: four groups of persons with lupus (n=29), three groups of
      rheumatologists (n=20), and one group of allied health professionals (n=8). The
      groups were held in British Columbia, Ontario, and Quebec. All sessions were
      audio-recorded and transcribed verbatim. Qualitative analysis was performed using
      grounded theory. The transcripts were reviewed independently and coded by the
      moderator and co-moderator using 1) qualitative data analysis software developed
      by Provalis Research, Montreal, Canada, and 2) manual coding. RESULTS: Four main
      themes emerged: 1) specific information and resource needs; 2) barriers to
      engagement in health care; 3) facilitators of engagement in health care; and 4)
      tools identified as helpful for the self-management of lupus. CONCLUSION: These
      findings will help guide the scope of LINTM with relevant information topics and
      specific tools that will be most helpful to the diverse needs of persons with
      lupus and their health care providers.

PMID- 24335013
TI  - FAF and SufA: proteins of Finegoldia magna that modulate the antibacterial
      activity of histones.
AB  - Many bacterial pathogens have developed methods to overcome the defences of the
      host innate immune system. One such defence is the release of antimicrobial
      peptides (AMPs). Histones have been found to function as AMPs, in addition to
      their main biological function of packaging and organising DNA into nucleosomes.
      In this study, the Gram-positive anaerobic coccus Finegoldia magna was found to
      bind histones by Western blot and immunoprecipitation analysis. F. magna, which
      is normally a commensal of the skin and mucous membranes, is also known to act as
      an opportunistic pathogen and has been isolated from various clinical infection
      sites. It was found to bind to histones extracted from human skin epidermis
      through its surface and extracellular adhesion protein FAF. Through FAF binding,
      F. magna was protected from histone bactericidal activity. Furthermore, the
      histones were found to be degraded by SufA, a subtilisin-like extracellular
      serine protease of F. magna. Hence, the results of the present study will give
      more insight into how F. magna persists both as a commensal organism at the
      basement membrane of the skin and as an opportunistic pathogen during infection.

PMID- 24335014
TI  - Conical polyurethane implants: an uplifting augmentation.
AB  - BACKGROUND: Polyurethane-coated conical implants were introduced by Silimed (US
      distributor: Sientra, Santa Barbara, California) in 2008 and offer an alternative
      to round or anatomically shaped implants. By their design and volume
      distribution, they naturally create central volume and give a reasonable fullness
      to the upper pole while lifting some ptotic breasts, thus avoiding the need for
      classical mastopexy. OBJECTIVES: The authors discuss the advantages of conical
      implants as an alternative to conventional silicone implants for women with
      breast ptosis. METHODS: In the 2-year period between December 2010 and December
      2012, a consecutive series of 302 women underwent implant-based breast surgery
      procedures (236 primary augmentations, 59 revisions, and 7 mastopexy
      augmentations) with conical polyurethane devices. Implant volumes ranged from 225
      to 560 cc, with low- to medium-profile devices predominating. No extra-high
      profile implants were used. Only 1 patient had a drain inserted on completion of
      a revision augmentation. RESULTS: There were no infections (0%) and no wound
      dehiscence (0%). Four cases required reoperation (1.3%). Patient satisfaction
      scores were universally high (average, 9.94/10). There have been no capsular
      contractures to date, but follow-up is short. CONCLUSION: The modern conical,
      polyurethane implant has many advantages over the conventional round or
      anatomically shaped implants and offers patients an ideal compromise between
      volume, natural upper pole fullness, and a lift without mastopexy scars.

PMID- 24335015
TI  - Commentary on: Nipple areola reconstructing reduction mammaplasty.

PMID- 24335016
TI  - Nonexcisional tissue tightening: creating skin surface area reduction during
      abdominal liposuction by adding radiofrequency heating.
AB  - BACKGROUND: Recent publications show that heat-mediated tissue tightening is a
      promising treatment for the lax abdomen and may provide better long-term outcomes
      than traditional suction-assisted liposuction (SAL). OBJECTIVES: The author
      evaluates the degree and duration of skin surface area contraction, as well as
      the influence of anatomic location of the treatment region on the degree of
      tissue tightening, in a study comparing SAL alone vs SAL plus radiofrequency
      assisted liposuction (RFAL). METHODS: In this prospective, randomized, split
      abdominal study, 12 consecutive patients were treated with SAL alone on 1 side
      and with SAL plus RFAL on the other side. Each patient had 4 (3 * 3-cm) squares-2
      per treatment type-tattooed in the lower abdominal region (2 on the right and 2
      on the left). The surface area of these squares was measured with the Vectra
      computerized measurement system (Canfield, Inc, Fairfield, New Jersey) at
      pretreatment, at 6 weeks posttreatment, and at 1 year posttreatment. All
      measurements were subjected to statistical analysis using predictive analytic
      software and were evaluated for statistical significance. RESULTS: In regions
      treated with SAL alone, there was a 10.4% mean skin surface area contraction at 6
      weeks and 8.3% at 1 year posttreatment. The mean skin surface area reduction was
      25.8% in regions treated with radiofrequency plus SAL at 6 weeks and at 1 year.
      The anatomic location of each square (medial vs lateral) did not statistically
      correlate with more or less tissue tightening. CONCLUSIONS: Radiofrequency
      assisted tissue tightening, when applied in conjunction with SAL, is effective in
      achieving greater skin surface area reduction.

PMID- 24335017
TI  - Impact of MiR-21 on the expression of FasL in the presence of TGF-beta1.
AB  - BACKGROUND: Micro-ribonucleic acids (miR) are small, noncoding RNA molecules 19
      to 25 nucleotides in length that typically function as negative regulators of
      expression for many target genes involved in cell proliferation, differentiation,
      and apoptosis. However, the effects of miR-21 on keloid fibroblasts are currently
      unknown. OBJECTIVES: The authors investigate whether miR-21, a specific miR
      implicated in multiple aspects of keloid fibroblasts, affects the expression of
      Fas ligand (FasL) in the presence of transforming growth factor (TGF)-beta1.
      METHODS: The relationship between TGF-beta1 and miR-21 expression was
      investigated by TaqMan quantitative real-time polymerase chain reaction (Life
      Technologies, Grand Island, New York). FasL protein was determined by Western
      blotting, and regulation of cell proliferation/migration/apoptosis ability by TGF
      beta1 inhibitor or plasmid was evaluated respectively by EdU incorporation,
      Transwell assay, and flow cytometry analysis. RESULTS: Fibroblasts from keloid
      tissue were confirmed to express high levels of TGF-beta1 and miR-21 compared
      with normal skin fibroblasts. Expression of TGF-beta1 and miR-21 was positively
      correlated in fibroblasts. In addition, cells transfected with TGF-beta1
      inhibitor or miR-21 inhibitor showed significant increases in FasL protein levels
      and number of apoptotic cells compared with control cells, whereas cell growth
      and migration significantly decreased. The opposite results could also be
      confirmed when TGF-beta1 was upregulated in normal skin fibroblasts. CONCLUSIONS:
      TGF-beta1 could effectively influence cell proliferation, apoptosis, and
      migration via its control of miR-21. These findings also identify a novel
      mechanism of interaction between TGF-beta1 and miR-21 in the regulation of FasL
      protein, which is involved in keloid formation.

PMID- 24335018
TI  - Why read journals, anyway?

PMID- 24335019
TI  - Going in the wrong direction with monsplasty.

PMID- 24335020
TI  - Response to "Going in the wrong direction with monsplasty".

PMID- 24335021
TI  - Response to "Going in the wrong direction with monsplasty".

PMID- 24335022
TI  - Aesthetic or functional indications for liposuction.

PMID- 24335024
TI  - Separating the contributions of olivocochlear and middle ear muscle reflexes in
      modulation of distortion product otoacoustic emission levels.
AB  - OBJECTIVES: Mediated by the medial olivocochlear system (MOCS), distortion
      product otoacoustic emission (DPOAE) levels are reduced by presentation of
      contralateral acoustic stimuli. Such acoustic signals can also evoke a middle ear
      muscle reflex (MEMR) that also attenuates recorded DPOAE levels. Our aim is to
      clearly differentiate these two inhibitory mechanisms and to analyze each
      separately, perhaps allowing the development of novel tests of hearing function.
      METHODS: DPOAE were recorded in real time from chinchillas with normal auditory
      brainstem response thresholds and middle ear function. Amplitude reduction and
      its onset latency caused by contralateral presentation of intermittent narrow
      band noise (NBN) were measured. Stapedius and tensor tympani muscle tendons were
      divided without disturbing the ossicular chain, and DPOAE testing was repeated.
      RESULTS: Peak reduction of (2f1 - f2) DPOAE levels occurred when the center
      frequency of contralateral NBN approximated the primary tone f2, indicating an f2
      frequency-specific response. For a 4.5-kHz centered NBN, DPOAE (f2 = 4.4 kHz)
      inhibition was 0.1 dB (p < 0.001). This response remained present after tendon
      division, consistent with an MOCS origin. Low-frequency NBN (center frequency:
      0.5 kHz) reduced otoacoustic emission levels (0.1 dB, p < 0.001) across a wide
      range of DPOAE frequencies. This low-frequency response was abolished by division
      of the middle ear muscle tendons, clearly indicating MEMR involvement.
      CONCLUSIONS: Following middle ear muscle tendon division, DPOAE inhibition by
      contralateral stimuli approximating the primary tone f2 persists, whereas
      responses evoked by lower contralateral frequencies are abolished. This
      distinguishes the different roles of the MOCS (f2 frequency specific) and MEMR
      (low frequency only) in contralateral modulation of DPOAE. This analysis helps
      clarify the pathways involved in an objective test that might have clinical
      benefit in the testing of neonates.

PMID- 24335025
TI  - Images in vascular medicine. Celiac trunk aneurysm in a patient with Adamantiades
      Behcet disease.

PMID- 24335026
TI  - Protective effect of metformin on myocardial injury in metabolic syndrome
      patients following percutaneous coronary intervention.
AB  - OBJECTIVES: The present study tested the hypothesis that pretreatment with
      metformin decreases postprocedural myocardial injury and improves clinical
      outcomes in metabolic syndrome patients following percutaneous coronary
      intervention (PCI). METHODS: We enrolled 152 metabolic syndrome patients with no
      prior history of metformin treatment. Patients scheduled for elective coronary
      intervention were randomized to the metformin or control group 7 days before the
      procedure. Creatine kinase-MB (CK-MB) and troponin I levels were measured at
      baseline and 8 and 24 h after the procedure, and clinical outcomes were monitored
      for 1 year. RESULTS: Post-PCI myocardial injury as indicated by CK-MB elevation
      (14.5 vs. 32.9%, p = 0.008) and troponin I elevation (14.5 vs. 34.2%, p = 0.005)
      was significantly lower in the metformin group than in the control group.
      Postprocedural peak values of CK-MB (2.70 +/- 4.30 vs. 6.29 +/- 8.03 ng/ml, p <
      0.001) and troponin I (0.02 +/- 0.05 vs. 0.07 +/- 0.10 ng/ml, p = 0.001) were
      also significantly lower in the metformin group than in the control group. At 1
      year, the composite endpoint of death from any cause, post-PCI myocardial
      infarction (MI), MI after PCI hospitalization or ischemia-driven target lesion
      revascularization occurred in 7.9% of metformin-treated patients and 28.9% of
      controls (hazard ratio 0.25, 95% CI 0.10-0.62, log rank p = 0.001). CONCLUSIONS:
      A 7-day metformin pretreatment regimen (250 mg 3 times a day) significantly
      reduces postprocedural myocardial injury and improves 1-year clinical outcomes in
      metabolic syndrome patients undergoing PCI.

PMID- 24335027
TI  - The mouse that lost its appetite for human.
AB  - In this issue of Blood, Lavender et al take an important step forward in the
      development of humanized mouse models and particularly for the analysis of human
      immunity.

PMID- 24335029
TI  - Platelet von Willebrand factor: sweet resistance.
AB  - In this issue of Blood, McGrath et al show that the terminal glycan structures of
      platelet von Willebrand factor (VWF) are markedly different compared with such
      structures present on plasma VWF.1 Unexpectedly, these differences endow platelet
      VWF with a specific resistance against proteolysis by the VWF-cleaving protease
      ADAMTS13, thereby potentially increasing the hemostatic potential of platelet VWF
      during the formation of platelet-rich thrombi.

PMID- 24335028
TI  - Spotlight on FLI1, RUNX1, and platelet dysfunction.
AB  - In this issue of Blood, Stockley et al describe mutations in FLI1 and RUNX1,
      identified by next-generation sequencing (NGS) studies, in 6 of 13 patients with
      excessive bleeding and impaired platelet dense granule secretion, and highlight
      transcription factor (TF) mutations as an important mechanism for inherited
      platelet dysfunction.

PMID- 24335030
TI  - Donating used CARs.
AB  - In this issue of Blood, Kochenderfer et al show that engineered CD19-chimeric
      antigen receptor (CAR) and donor-derived allogeneic T cells can safely treat CD19
      positive B-cell malignancies, which have relapsed after allogeneic stem cell
      transplantation.

PMID- 24335031
TI  - Shockingly: the loss of Lyn leads to leakiness.
AB  - In this issue of Blood, Han et al demonstrate that endotoxin-induced mortality in
      a murine model of acute lung injury (ALI) was associated with increased vascular
      permeability attributable to loss of the Src family kinase (SFK) Lyn.

PMID- 24335032
TI  - The neural correlates of reading fluency deficits in children.
AB  - Multiple studies have shown that individuals with a reading disability (RD)
      demonstrate deficits in posterior left-hemispheric brain regions during reading
      related tasks. These studies mainly focused on reading sub-skills, and it remains
      debated whether such dysfunction is apparent during more ecologically valid
      reading skills, such as reading fluency. In this fMRI study, reading fluency was
      systematically varied to characterize neural correlates of reading fluency in 30
      children with (RD) and without (typical developing children, TYP) a RD. Sentences
      were presented at constrained, comfortable, and accelerated speeds, which were
      determined based on individual reading speed. Behaviorally, RD children displayed
      decreased performance in several reading-related tasks. Using fMRI, we
      demonstrated that both TYP and RD children display increased activation in
      several components of the reading network during fluent reading. When required to
      read at an accelerated speed, RD children exhibited less activation in the
      fusiform gyrus (FG) compared with the TYP children. A region of interest analysis
      substantiated differences in the FG and demonstrated a relationship to behavioral
      reading performance. These results suggest that the FG plays a key role in fluent
      reading and that it can be modulated by speed. These results and their
      implications for remediation strategies should be considered in educational
      practice.

PMID- 24335034
TI  - Heterozygous IGFALS gene variants in idiopathic short stature and normal
      children: impact on height and the IGF system.
AB  - BACKGROUND: In acid-labile subunit (ALS)-deficient families, heterozygous
      carriers of IGFALS gene mutations are frequently shorter than their wild-type
      relatives, suggesting that IGFALS haploinsufficiency could result in short
      stature. We have characterized IGFALS gene variants in idiopathic short stature
      (ISS) and in normal children, determining their impact on height and the IGF
      system. PATIENTS AND METHODS: In 188 normal and 79 ISS children levels of IGF-1,
      IGFBP-3, ALS, ternary complex formation (TCF) and IGFALS gene sequence were
      determined. RESULTS: In sum, 9 nonsynonymous or frameshift IGFALS variants
      (E35Gfs*17, G83S, L97F, R277H, P287L, A330D, R493H, A546V and R548W) were found
      in 10 ISS children and 6 variants (G170S, V239M, N276S, R277H, G506R and R548W)
      were found in 7 normal children. If ISS children were classified according to the
      ability for TCF enhanced by the addition of rhIGFBP-3 (TCF+), carriers of
      pathogenic IGFALS gene variants were shorter and presented lower levels of IGF-1,
      IGFBP-3 and ALS in comparison to carriers of benign variants. In ISS families,
      subjects carrying pathogenic variants were shorter and presented lower IGF-1,
      IGFBP-3 and ALS levels than noncarriers. CONCLUSIONS: These findings suggest that
      heterozygous IGFALS gene variants could be responsible for short stature in a
      subset of ISS children with diminished levels of IGF-1, IGFBP-3 and ALS.

PMID- 24335033
TI  - Development of human brain structural networks through infancy and childhood.
AB  - During human brain development through infancy and childhood, microstructural and
      macrostructural changes take place to reshape the brain's structural networks and
      better adapt them to sophisticated functional and cognitive requirements.
      However, structural topological configuration of the human brain during this
      specific development period is not well understood. In this study, diffusion
      magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25
      preadolescents were acquired to characterize network dynamics at these 3 landmark
      cross-sectional ages during early childhood. dMRI tractography was used to
      construct human brain structural networks, and the underlying topological
      properties were quantified by graph-theory approaches. Modular organization and
      small-world attributes are evident at birth with several important topological
      metrics increasing monotonically during development. Most significant increases
      of regional nodes occur in the posterior cingulate cortex, which plays a pivotal
      role in the functional default mode network. Positive correlations exist between
      nodal efficiencies and fractional anisotropy of the white matter traced from
      these nodes, while correlation slopes vary among the brain regions. These results
      reveal substantial topological reorganization of human brain structural networks
      through infancy and childhood, which is likely to be the outcome of both
      heterogeneous strengthening of the major white matter tracts and pruning of other
      axonal fibers. 

PMID- 24335035
TI  - Serodiagnosis of Mycobacterium avium complex pulmonary disease in rheumatoid
      arthritis.
AB  - BACKGROUND: Mycobacterium avium complex (MAC) pulmonary disease (PD) is often
      difficult and complicated to diagnose or to discriminate from follicular
      bronchitis, bronchiectasis, or other conditions associated with rheumatoid
      arthritis (RA) lung in the clinical setting. OBJECTIVE: We investigated whether a
      serologic test for anti-glycopeptidolipid (GPL) antibody was useful for
      distinguishing MAC-PD from RA lung in diagnosis. METHODS: Serum IgA antibody to
      MAC-specific GPL core antigen was measured by an enzyme immunoassay. Antibody
      levels were measured in sera from 14 RA patients with MAC-PD (RA + MAC), 20 RA
      patients with bronchial or bronchiolar lesions without MAC-PD (RA w/o MAC), 20 RA
      patients without pulmonary lesions (RA only), and 25 healthy volunteers (HV).
      RESULTS: The levels of serum anti-GPL antibodies were higher in the RA + MAC
      group than in the RA w/o MAC, RA-only, and HV groups (2.87 +/- 2.83 vs. 0.50 +/-
      0.45, 0.31 +/- 0.24, and 0.38 +/- 0.10 U/ml, respectively; p < 0.001). With the
      cutoff point in receiver-operating characteristic analysis set at 0.7 U/ml, the
      serologic test differentiated RA + MAC from RA w/o MAC with a sensitivity of 100%
      and specificity of 90%. CONCLUSIONS: This serologic test for anti-GPL antibody is
      useful for diagnosing MAC-PD in RA.

PMID- 24335036
TI  - Metabolic syndrome.

PMID- 24335037
TI  - Other types of primary hyperlipoproteinemia(hyperlipidemia). Executive summary of
      the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and
      prevention of atherosclerotic cardiovascular diseases in Japan--2012 version.

PMID- 24335038
TI  - Coronary artery disease. Executive summary of the Japan Atherosclerosis Society
      (JAS) guidelines for the diagnosis and prevention of atherosclerotic
      cardiovascular diseases in Japan--2012 version.

PMID- 24335039
TI  - Treatment B) drug therapy: executive summary of the Japan Atherosclerosis
      Society(JAS) guidelines for the diagnosis and prevention of atherosclerotic
      cardiovascular diseases in Japan--2012 version.

PMID- 24335040
TI  - Diabetes mellitus. Executive summary of the Japan Atherosclerosis Society (JAS)
      guidelines for the diagnosis and prevention of atherosclerotic cardiovascular
      diseases in Japan--2012 version.

PMID- 24335041
TI  - Chronic kidney disease.

PMID- 24335042
TI  - Cerebrovascular diseases.

PMID- 24335043
TI  - The elderly.

PMID- 24335044
TI  - Women. Executive Summary of the Japan Atherosclerosis Society (JAS) Guidelines
      for the Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases in
      Japan--2012 Version.

PMID- 24335045
TI  - Diagnosis of atherosclerosis. Executive Summary of the Japan Atherosclerosis
      Society (JAS) Guidelines for the Diagnosis and Prevention of Atherosclerotic
      Cardiovascular Diseases in Japan--2012 Version.

PMID- 24335046
TI  - Familial hypercholesterolemia.

PMID- 24335047
TI  - Kidney function, cholesterol absorption and remnant lipoprotein accumulation in
      patients with diabetes mellitus.
AB  - AIM: Remnant lipoproteins are atherogenic and increased in patients with type 2
      diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus
      far, information is limited regarding the synthesis and absorption of cholesterol
      in CKD patients and a possible link to the remnant levels. We examined possible
      alterations in serum markers of cholesterol synthesis and absorption and their
      potential associations with remnant lipoproteins in patients with CKD. METHODS:
      The subjects included 146 consecutive patients with T2DM in various stages of
      CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C),
      lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol
      absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated
      glomerular filtration rate (eGFR) were used to describe the degree of CKD.
      RESULTS: The median (interquartile range) levels of RemL-C, lathosterol and
      campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) MUg/mL and 2.3 (1.7-3.0)
      MUg/mL, respectively. The RemL-C level was positively correlated with the U-ACR
      and inversely correlated with the eGFR. The RemL-C level was positively
      correlated with both the lathosterol and campesterol levels. The lathosterol
      level was not significantly correlated with the U-ACR, although it was positively
      correlated with the eGFR. In contrast, the campesterol level was positively
      correlated with the ACR and inversely with the eGFR. In the multiple regression
      analysis, both lathosterol and campesterol were positively associated with the
      RemL-C level, independent of the U-ACR, eGFR and other variables. CONCLUSIONS:
      The serum campesterol concentrations are higher in patients with a greater degree
      of albuminuria and a lower renal funtion. In this study, the markers of
      cholesterol absorption and synthesis were independent determinants of the RemL-C
      level. Increased intestinal cholesterol absorption may be an additional mechanism
      for remnant accumulation in T2DM patients with CKD.

PMID- 24335049
TI  - Sex determination in insects: variations on a common theme.
AB  - Recent studies in a representative selection of holometabolous insects suggest
      that, despite diversity at the instructive level, the signal-relaying part of the
      sex-determining pathway is remarkably well conserved. In principle, it is
      composed of the transformer gene (tra), which acts as a common binary switch that
      transduces the selected sexual fate, female when ON, male when OFF, to the
      downstream effector doublesex(dsx) that controls overt sexual differentiation. An
      interesting recurrent feature is that tra is switched ON in the early zygote by
      maternally provisioned tra activity. Different male-determining signals evolved,
      which prevent maternal activation of zygotic tra to allow for male development.
      In some species, where lack of maternal activation leaves tra in the OFF state,
      novel female-determining signals were deployed to activate zygotic tra. It
      appears that both the instructive end of the pathway upstream of tra as well as
      the executive end downstream of dsx are primary targets of evolutionary
      divergence, while the transduction part seems less prone to changes. We propose
      that this is a feature shared with many other signaling cascades that regulate
      developmental fates.

PMID- 24335048
TI  - Physical activity and cognition in the northern Manhattan study.
AB  - BACKGROUND: To test the hypothesis that leisure time physical activity (PA) is
      associated with cognitive status. METHODS: We assessed cognition using the Mini
      Mental Status Examination (MMSE) at enrollment and using the modified Telephone
      Interview for Cognitive Status (TICS-m) administered annually since 2001 in the
      Northern Manhattan Study. Baseline measures of leisure time PA were collected via
      in-person questionnaires. Total PA was categorized into 3 groups based on the
      metabolic equivalent (MET) score, a composite of total reported intensity and
      time. We used linear regression models to examine the association of PA with
      MMSE, and generalized estimating equations for change in TICS-m over time.
      RESULTS: There were 3,298 stroke-free participants with MMSE data (mean MMSE 26.0
      +/- 3.8) and 2,279 with TICS-m scores available. Compared to no PA, those with
      the upper quartile of MET scores had greater baseline MMSE scores (adjusted beta
      = 0.4, p = 0.01) but no association with change in TICS-m over time. There were
      interactions (p < 0.05) between PA and both insurance and education; compared to
      no PA, those in the upper quartile of MET scores had a greater MMSE score only
      among those with Medicaid/no insurance (adjusted beta = 0.83, p = 0.0005) and
      those who did not complete high school (adjusted beta = 0.68, p = 0.001).
      CONCLUSIONS: Increased levels of PA were associated with better baseline MMSE,
      particularly among those with socioeconomic disadvantages, but not with cognitive
      decline.

PMID- 24335050
TI  - Brain. Editorial.

PMID- 24335051
TI  - Rewiring the ischaemic brain with human-induced pluripotent stem cell-derived
      cortical neurons.

PMID- 24335054
TI  - How do pregnancy-related weight changes and breastfeeding relate to maternal
      weight and BMI-adjusted waist circumference 7 y after delivery? Results from a
      path analysis.
AB  - BACKGROUND: Reproduction has been related to long-term maternal weight gain, and
      changes in fat mass, with gestational weight gain, have been identified as an
      important contributor. However, the influence of weight changes during the whole
      reproductive cycle and the modifying effect of breastfeeding are unknown.
      OBJECTIVE: The objective was to examine how prepregnancy weight, gestational
      weight gain, postpartum weight changes, and breastfeeding influence maternal
      weight and body mass index-adjusted waist circumference (WCBMI) 7 y after
      delivery. DESIGN: This was a prospective cohort study of 23,701 women
      participating in the Danish National Birth Cohort with singleton births and no
      births during follow-up. Path analysis was used to assess the total, direct, and
      indirect effects; the latter was mediated through weight changes on the pathways.
      RESULTS: Postpartum weight retention at 6 mo and weight gain from 6 to 18 mo
      postpartum were highly positively associated with both outcomes. A 1-kg increase
      in weight retention at 6 mo postpartum corresponded to an average increase of 0.5
      kg at 7 y. Gestational weight gain was not associated with WCBMI but was
      positively associated with weight at 7 y; 87% of this effect was mediated through
      later weight changes. For both outcomes, a small inverse association was observed
      for breastfeeding duration. This was strongest for WCBMI, for which 97% of the
      effect was direct, ie, not mediated through postpartum weight. CONCLUSIONS: These
      findings show that postpartum weight retention at 6 mo and weight gain from 6 to
      18 mo postpartum contribute equally to adverse maternal anthropometric measures 7
      y after delivery. Breastfeeding duration may have a beneficial effect.

PMID- 24335055
TI  - Vitamin D supplementation increases calcium absorption without a threshold
      effect.
AB  - BACKGROUND: The maximal calcium absorption in response to vitamin D has been
      proposed as a biomarker for vitamin D sufficiency. OBJECTIVE: The objective was
      to determine whether there is a threshold beyond which increasing doses of
      vitamin D, or concentrations of serum 25-hydroxyvitamin D [25(OH)D], no longer
      increase calcium absorption. DESIGN: This was a placebo-controlled, dose
      response, randomized, double-blind study of the effect of vitamin D on calcium
      absorption in healthy postmenopausal women. Seventy-six healthy postmenopausal
      women were randomly assigned to placebo or 800 IU (20 MUg), 2000 IU (50 MUg), or
      4000 IU (100 MUg) vitamin D3 for 8 wk. The technique of dual isotopes of stable
      calcium was used with a calcium carrier to measure calcium absorption at baseline
      and after 8 wk. RESULTS: Seventy-one women with a mean +/- SD age of 58.8 +/- 4.9
      y completed the study. The mean calcium intake was 1142 +/- 509 mg/d and serum
      25(OH)D was 63 +/- 14 nmol/L at baseline. A statistically significant linear
      trend of an increase in calcium absorption adjusted for age and body mass index
      with increasing vitamin D3 dose or serum 25(OH)D concentration was observed. A
      6.7% absolute increase in calcium absorption was found in the highest vitamin D3
      group (100 MUg). No evidence of nonlinearity was observed in the dose-response
      curve. CONCLUSIONS: No evidence of a threshold of calcium absorption was found
      with a serum 25(OH)D range from 40 to 130 nmol/L. Calcium absorption in this
      range is not a useful biomarker to determine nutritional recommendations for
      vitamin D.

PMID- 24335056
TI  - Variants in glucose- and circadian rhythm-related genes affect the response of
      energy expenditure to weight-loss diets: the POUNDS LOST Trial.
AB  - BACKGROUND: Circadian rhythm has been shown to be related to glucose metabolism
      and risk of diabetes, probably through effects on energy balance. Recent genome
      wide association studies identified variants in circadian rhythm-related genes
      (CRY2 and MTNR1B) associated with glucose homeostasis. OBJECTIVE: We tested
      whether CRY2 and MTNR1B genotypes affected changes in measures of energy
      expenditure in response to a weight-loss diet intervention in a 2-y randomized
      clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies)
      LOST Trial. DESIGN: The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963
      (n = 722) were genotyped in overweight or obese adults who were randomly assigned
      to 1 of 4 weight-loss diets that differed in their proportions of macronutrients.
      Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured.
      RESULTS: By 2 y of diet intervention, the A allele of CRY2 rs11605924 was
      significantly associated with a greater reduction in RQ (P = 0.03) and a greater
      increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was
      significantly associated with a greater increase in RQ (P = 0.01) but was not
      related to changes in RMR and RMR/kg. In addition, we found significant gene-diet
      fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction <
      0.001) in relation to 2-y changes in RQ. CONCLUSIONS: Our data indicate that
      variants in the circadian-related genes CRY2 and MTNR1B may affect long-term
      changes in energy expenditure, and dietary fat intake may modify the genetic
      effects. This trial was registered at www.clinicaltrials.gov as NCT00072995.

PMID- 24335057
TI  - Fish intake during pregnancy, fetal growth, and gestational length in 19 European
      birth cohort studies.
AB  - BACKGROUND: Fish is a rich source of essential nutrients for fetal development,
      but in contrast, it is also a well-known route of exposure to environmental
      pollutants. OBJECTIVE: We assessed whether fish intake during pregnancy is
      associated with fetal growth and the length of gestation in a panel of European
      birth cohort studies. DESIGN: The study sample of 151,880 mother-child pairs was
      derived from 19 population-based European birth cohort studies. Individual data
      from cohorts were pooled and harmonized. Adjusted cohort-specific effect
      estimates were combined by using a random- and fixed-effects meta-analysis.
      RESULTS: Women who ate fish >1 time/wk during pregnancy had lower risk of preterm
      birth than did women who rarely ate fish (<= 1 time/wk); the adjusted RR of fish
      intake >1 but <3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake >= 3
      times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher
      intake of fish during pregnancy gave birth to neonates with a higher birth weight
      by 8.9 g (95% CI: 3.3, 14.6 g) for >1 but <3 times/wk and 15.2 g (95% CI: 8.9,
      21.5 g) for >= 3 times/wk independent of gestational age. The association was
      greater in smokers and in overweight or obese women. Findings were consistent
      across cohorts. CONCLUSION: This large, international study indicates that
      moderate fish intake during pregnancy is associated with lower risk of preterm
      birth and a small but significant increase in birth weight.

PMID- 24335058
TI  - Potential effect of salt reduction in processed foods on health.
AB  - BACKGROUND: Excessive salt intake has been associated with hypertension and
      increased cardiovascular disease morbidity and mortality. Reducing salt intake is
      considered an important public health strategy in the Netherlands. OBJECTIVE: The
      objective was to evaluate the health benefits of salt-reduction strategies
      related to processed foods for the Dutch population. DESIGN: Three salt-reduction
      scenarios were developed: 1) substitution of high-salt foods with low-salt foods,
      2) a reduction in the sodium content of processed foods, and 3) adherence to the
      recommended maximum salt intake of 6 g/d. Health outcomes were obtained in 2
      steps: after salt intake was modeled into blood pressure levels, the Chronic
      Disease Model was used to translate modeled blood pressures into incidences of
      cardiovascular diseases, disability-adjusted life years (DALYs), and life
      expectancies. Health outcomes of the scenarios were compared with health outcomes
      obtained with current salt intake. RESULTS: In total, 4.8% of acute myocardial
      infarction cases, 1.7% of congestive heart failure cases, and 5.8% of stroke
      cases might be prevented if salt intake meets the recommended maximum intake. The
      burden of disease might be reduced by 56,400 DALYs, and life expectancy might
      increase by 0.15 y for a 40-y-old individual. Substitution of foods with
      comparable low-salt alternatives would lead to slightly higher salt intake
      reductions and thus to more health gain. The estimates for sodium reduction in
      processed foods would be slightly lower. CONCLUSION: Substantial health benefits
      might be achieved when added salt is removed from processed foods and when
      consumers choose more low-salt food alternatives.

PMID- 24335059
TI  - Characteristics and prognosis of hearing loss associated with Vogt-Koyanagi
      Harada disease.
AB  - OBJECTIVE: To clarify the characteristics and prognosis of hearing loss
      associated with Vogt-Koyanagi-Harada (VKH) disease. METHODS: We retrospectively
      examined 85 patients diagnosed with VKH disease between January 1996 and December
      2012. The control group included age- and gender-matched individuals without
      definitive ear disease. The patients with VKH disease were treated with high-dose
      systemic corticosteroids, which were tapered off gradually over a period of 6
      months or more by the treating ophthalmologists according to the severity of the
      ocular inflammation. The features of hearing loss were analyzed based on pure
      tone audiometric data obtained at the initial presentation according to
      diagnostic criteria based on the ISO 7029 standard. The efficacy of
      corticosteroid therapy was evaluated by audiometry at the initial presentation
      and during therapy for 3-6 months. RESULTS: In patients with VKH disease, the
      rate of hearing loss detected by audiometry was significantly higher than that of
      either subjective hearing loss (p < 0.001) or tinnitus (p < 0.001). Bilateral
      symmetrical hearing loss was the most common type of auditory disturbance
      associated with VKH disease. The degree of hearing loss was generally low, with
      no patients showing profound hearing loss. Hearing thresholds were significantly
      elevated at high frequencies compared with those at low-to-mid frequencies (p <
      0.001). Hearing thresholds at all frequencies after high-dose corticosteroid
      therapy were significantly better than those at initial presentation (p < 0.001),
      and the rate of patients who returned to within normal-range pure tone thresholds
      at all frequencies was 74.8%. CONCLUSIONS: As auditory manifestations cannot be
      detected through history taking alone, audiometry should be performed to evaluate
      hearing loss associated with VKH disease. Early administration of high-dose
      systemic corticosteroids is effective for treating the auditory manifestations,
      which generally show a relatively good short-term prognosis.

PMID- 24335060
TI  - Preface: The aging eye: normal changes, age-related diseases, and sight-saving
      approaches.
AB  - This volume presents articles based on a workshop held June 14 to 16, 2013 in
      Rancho Palos Verde, CA sponsored by the Ocular Research Symposia Foundation
      (ORSF). The mission of the ORSF is to focus attention on unmet needs and current
      research opportunities in eye research with the objective of accelerating
      translation of research findings to effective clinical care. In this workshop,
      the subject of the "The Aging Eye" was addressed, including the prevalence of eye
      diseases in aging and the economic burden imposed by these diseases. New research
      work was highlighted on the genetics, biology, biochemistry, neurochemistry, and
      the impact of nutrition and the environment on function in the older eye. By
      identifying "low-hanging fruit" (i.e., the best opportunities for successful
      transition of laboratory research for the prevention of and new treatments and
      cures for ocular diseases), we seek to spur funding at both the basic research
      and clinical levels, resulting in sight-saving and sight-restoration measures in
      the near future.

PMID- 24335061
TI  - Projected prevalences of age-related eye diseases.
AB  - PURPOSE: To examine projections of age-related eye diseases in the United States
      for health care planning. METHODS: Review of published scientific articles,
      census data, and unpublished research findings. RESULTS: The numbers of cases of
      all age-related eye diseases are expected to rise in the coming years. These
      projections are primarily based upon population projections, but give little
      consideration to changes in health behaviors, racial/ethnic differences,
      environmental exposures, and changes in health care practices that may influence
      estimates of costs of actual health care burden. CONCLUSIONS: Ongoing monitoring
      of trends in eye disease distribution is needed rather than projections based on
      old data that may be inadequate for generating reliable prediction models. There
      is a perpetual need to train new researchers with expertise in epidemiology, as
      the exigency for current prevalence estimates is crucial to maximize optimal
      visual health in the population.

PMID- 24335062
TI  - Vision problems are a leading source of modifiable health expenditures.
AB  - According to recent studies, visual problems represent one of the top
      contributors to economic health burden in the United States. This burden is
      divided nearly equally between direct expenditures for the care and treatment of
      visual problems, and the indirect costs of outcomes caused by low vision,
      including productivity losses, the cost of care, and incremental nursing home
      placements. A large amount of academic research is devoted to visual science, the
      biology of the visual system, and the medical treatment of visual disorders.
      Compared to the burden, a disproportionate share of this research is devoted to
      the study of retinal disorders and glaucoma. This is understandable, as research
      into the retina and optic nerve has the potential to unlock fundamental insights
      into the nature of sight and visual cognition. However, population visual health
      and the functionality that depends upon it also may benefit greatly from
      additional research into areas of prevention, rehabilitation, and adaptation. In
      addition, comparative research into the benefits of resource allocation across
      prevention, treatment, and rehabilitative resources could lead to improvements in
      population health.

PMID- 24335063
TI  - Anatomic alterations in aging and age-related diseases of the eye.
AB  - PURPOSE: We described anatomic age-related changes in the human eye to determine
      potential areas of investigation that may lead to identifying eyes at risk for
      age-related disease. METHODS: A descriptive review of anatomic changes in the eye
      related to aging was performed in the context of current areas of investigation.
      The review was performed specifically for differing anatomic ocular structures,
      including cornea, trabecular meshwork, lens, uveal tract, Bruch's membrane,
      retina, RPE, vitreous, sclera, and optic nerve. RESULTS: Age-related changes
      occur in all ocular tissues. The cornea flattens and there is an attrition of
      endothelial cells. The shape of the trabecular meshwork changes and there is a
      loss of trabecular endothelium. The lens grows and becomes cataractous. The
      ciliary body becomes collagenized, there are choroidal vascular changes, and
      Bruch's membrane thickens. Retinal vessels become hyalinized and there is a loss
      of rods before cones in the macula. RPE morphometric changes occur with aging.
      The vitreous becomes liquefied and there is a loss of vitreous
      compartmentalization. The sclera becomes rigid and may become calcified. The
      optic nerve exhibits structural changes with age. CONCLUSIONS: There are numerous
      anatomic age-related changes in the human eye. Current areas of investigation
      related to these changes include adaptive optics scanning laser ophthalmoscopy
      imaging of the RPE mosaic in the context of aging, and drug delivery devices that
      overcome age-related alterations to retinal and macular perfusion.

PMID- 24335064
TI  - Genetic and environmental underpinnings to age-related ocular diseases.
AB  - Age-related macular degeneration (AMD), cataract, glaucoma and diabetic
      retinopathy are common causes of visual loss. Both environmental and genetic
      factors contribute to the development of these diseases. The modifiable factors
      related to some of these age-related and visually threatening diseases are
      smoking, obesity, and dietary factors, and a cardiovascular risk profile. Many
      common and a few rare genetic factors are associated with AMD. The role of
      genetic variants for the other diseases are less clear. Interactions between
      environmental, therapeutic, and genetic factors are being explored. Knowledge of
      genetic risk and environmental factors, especially for AMD, has grown markedly
      over the past 2.5 decades and has led to some sight-saving approaches in
      preventive management.

PMID- 24335065
TI  - Common cell biologic and biochemical changes in aging and age-related diseases of
      the eye: toward new therapeutic approaches to age-related ocular diseases.

PMID- 24335066
TI  - Age-related changes in the visual pathways: blame it on the axon.
AB  - The aging visual system is marked by a decline in some, but not all, key
      functions. Some of this decline is attributed to changes in the optics of the
      eye, but other aspects must have a neural basis. Across mammals, with aging there
      is remarkable persistence of central structures to which retinal ganglion cell
      (RGC) axons project with little or no loss of neurons. Similarly, RGC bodies in
      the retina are subject to variable age-related loss, with most mammals showing
      none over time. In contrast, the RGC axon itself is highly vulnerable. Across
      species, the rate of axon loss in the optic nerve is related inversely to the
      total number of axons at maturity and lifespan. The result of this scaling is
      approximately a 40% total decline in axon number. Evidence suggests that the
      consistent vulnerability of RGC axons to aging arises from their high metabolic
      demand combined with diminishing resources. Thus, therapeutic interventions that
      conserve bioenergetics may have potential to abate age-related decline in visual
      function.

PMID- 24335067
TI  - Nutrition effects on ocular diseases in the aging eye.
AB  - PURPOSE: We reviewed the data from the clinical trials of nutritional supplements
      for the treatment of age-related cataract and age-related macular degeneration
      (AMD) to determine future directions of research and treatment. METHODS: Data
      from the controlled clinical trials are presented and reviewed for potential
      opportunities for further research into the treatment of cataracts and AMD.
      RESULTS: Two trials using daily multivitamins/minerals demonstrated a reduction
      in the progression of nuclear cataract, but increased the risk of posterior
      subcapsular cataract. For AMD, the Age-Related Eye Disease Study (AREDS)
      formulation (vitamins C, E, beta-carotene, zinc, and copper) reduced the risk of
      progression to advanced AMD by 25% at 5 years. Because beta-carotene is
      associated with increased lung cancer in former smokers, lutein/zeaxanthin could
      replace beta-carotene and provide an incremental increase in the beneficial
      effects beyond the effects of the AREDS formulation. In addition, a randomized
      clinical trial of B vitamins demonstrated a beneficial effect for AMD with the
      vitamin B complex. CONCLUSIONS: Future evaluation may include additional
      assessments of nutrients for the treatment of progression of cataract and AMD. A
      modest reduction would have significant impact as the numbers of persons affected
      with these two leading causes of blindness are projected to double in the next
      decade. An important step would be to develop surrogate outcomes to increase
      efficiency in clinical trials. More detailed phenotyping, especially of AMD, is
      required as it appears to be not one disease, but a group of diseases. Genotype
      phenotype analyses may help to target pathways that are important in AMD.

PMID- 24335068
TI  - Age-related changes and diseases of the ocular surface and cornea.
AB  - Aging of the ocular surface and corneal tissues, major components of the visual
      system, causes major eye disease and results in substantial cost in medical and
      social terms. These diseases include the highly prevalent dry eye disease that
      affects the ocular surface and its glands, leading to tear film alterations,
      discomfort, and decreased vision. Studies show that 14.4% of the population in
      the United States older than 50 years have dry eye disease and demonstrate that
      it is particularly prevalent among women. Annual medical costs per patient with
      dry eye in the United States are estimated at $783 per year, with an overall
      medical cost adjusted to prevalence of $3.84 billion per year. Societal costs,
      which include loss of productivity, are estimated per patient at $11,302 per
      year, with overall costs adjusted to prevalence of $55.4 billion per year.
      Because there are few effective treatments for the disease, more research on its
      etiology and mechanisms is warranted and needed. Increased public education about
      risk factors for the disease is also required. Another major age-related eye
      disease of the cornea that leads to vision impairment and potentially blindness
      if left untreated is Fuchs' endothelial corneal dystrophy. This disease leads to
      loss of the endothelial cells on the internal side of the cornea that are
      responsible for keeping the cornea in the proper hydration state to ensure its
      transparency to light. The mechanism of cell loss is unknown, and the only
      treatment available to date is surgical transplantation of the cornea or inner
      part of the cornea. These medically costly procedures require donor corneas, eye
      banking, and medical follow-up, with accrued costs. Fuchs' endothelial corneal
      dystrophy is a major cause of corneal transplantation in the United States;
      therefore, research support is needed to determine the mechanism of this age
      related disease, to develop medical, nonsurgical methods for treatment.

PMID- 24335069
TI  - The prevalence of age-related eye diseases and visual impairment in aging:
      current estimates.
AB  - PURPOSE: To examine prevalence of five age-related eye conditions (age-related
      cataract, AMD, open-angle glaucoma, diabetic retinopathy [DR], and visual
      impairment) in the United States. METHODS: Review of published scientific
      articles and unpublished research findings. RESULTS: Cataract, AMD, open-angle
      glaucoma, DR, and visual impairment prevalences are high in four different
      studies of these conditions, especially in people over 75 years of age. There are
      disparities among racial/ethnic groups with higher age-specific prevalence of DR,
      open-angle glaucoma, and visual impairment in Hispanics and blacks compared with
      whites, higher prevalence of age-related cataract in whites compared with blacks,
      and higher prevalence of late AMD in whites compared with Hispanics and blacks.
      The estimates are based on old data and do not reflect recent changes in the
      distribution of age and race/ethnicity in the United States population. There are
      no epidemiologic estimates of prevalence for many visually-impairing conditions.
      CONCLUSIONS: Ongoing prevalence surveys designed to provide reliable estimates of
      visual impairment, AMD, age-related cataract, open-angle glaucoma, and DR are
      needed. It is important to collect objective data on these and other conditions
      that affect vision and quality of life in order to plan for health care needs and
      identify areas for further research.

PMID- 24335070
TI  - Aging and age-related diseases of the ocular lens and vitreous body.
AB  - Reduced quality of life and financial burden due to visual impairment and
      blindness begin to increase dramatically when individuals reach the age of 40.
      The major causes of age-related vision loss can be traced to changes to the
      structure and function of the lens, one of the tissues responsible for focusing
      light on the retina. Age-related nuclear cataracts, which are caused by
      aggregation and condensation of proteins, diminish vision because they impede the
      transmission and focusing of light on the retina. In addition to the slow
      developing age-related form, cataracts often develop rapidly as a complication of
      ocular surgery, such as following vitrectomy or as a consequence of vitreous gel
      degeneration. Posterior capsular opacification, which can develop following
      cataract removal, is caused by proliferation and inappropriate accumulation of
      lens epithelial cells on the surfaces of intraocular lenses and the posterior
      lens capsule. Presbyopia is a loss of accommodative amplitude and reduced ability
      to shift focus from far to near objects. Onset of presbyopia is associated with
      an increase in lens hardness and reduced ability of the lens to change shape in
      response to ciliary muscle contraction. Avenues of promising research that seek
      to delay or prevent these causes of low vision are discussed in light of our
      current understanding of disease pathogenesis and some challenges that must be
      met to achieve success.

PMID- 24335071
TI  - Glaucoma: a disease of early cellular senescence.

PMID- 24335074
TI  - Age-related psychophysical changes and low vision.
AB  - When considering the burden of visual impairment on aging individuals and society
      at large, it is important to bear in mind that vision changes are a natural
      aspect of aging. In this article, we consider vision changes that are part of
      normal aging, the prevalence of abnormal vision changes caused by disorders of
      the visual system, and the anticipated incidence and impact of visual impairment
      as the US population ages. We then discuss the services available to reduce the
      impact of vision loss, and the extent to which those services can and should be
      improved, not only to be better prepared for the anticipated increase in low
      vision over the coming decades, but also to increase the awareness of
      interactions between visual impairment and comorbidities that are common among
      the elderly. Finally, we consider how to promote improved quality, availability,
      and acceptance of low vision care to lessen the impact of visual impairment on
      individuals, and its burden on society.

PMID- 24335073
TI  - Effects of diabetes on the eye.
AB  - Hyperglycemia has toxic effects on almost all cells in the body. Ophthalmic
      complications of hyperglycemia are most profound in cornea and retina. Seventy
      percent of diabetics suffer from corneal complications, collectively called
      diabetic keratopathy, which includes include recurrent erosions, delayed wound
      healing, ulcers, and edema. Confocal microscopy has permitted in vivo imaging of
      corneal nerves, which are also affected in diabetic subjects. Gene therapies
      upregulating MNNG HOS transforming gene (cMet) and/or downregulating MMP10 and
      cathepsin S are potential future therapies for diabetic keratopathy. Diabetic
      retinopathy (DR) is the most common cause of blindness in people over the age of
      50. There is accumulating evidence that DR is an inflammatory disease. The
      initial events in animal models of DR are increased vascular permeability and
      leukostasis. This binding of leukocytes to the endothelium results from an
      increase in intracellular adhesion molecule-1 (ICAM-1) on the retinal capillary
      endothelium (EC) and expression of CD11/CD18 on the surface of the activated
      leukocyte. We have observed polymorphonuclear leukocytes (PMNs) at sites of EC
      vascular dysfunction in diabetic retinas as well as choroid. Anti-inflammatory
      drugs like etanercept, aspirin, or meloxicam reduce leukostasis and EC death.
      Future therapies may include repopulation of the acellular capillaries after EC
      and pericyte death with vascular progenitors made from the patient's own blood
      cells.

PMID- 24335075
TI  - Well-leg compartment syndrome after fracture fixation in hemilithotomy position:
      case report of a preventable condition.
AB  - OBJECTIVE: To report a case of subtrochanteric femur fracture that led to
      intraoperative compartment syndrome in the well leg. CLINICAL PRESENTATION AND
      INTERVENTION: A 28-year-old obese male who presented with a comminuted
      subtrochanteric fracture underwent a prolonged open reduction and internal
      fixation using dynamic condylar screw. In the postoperative period, after the
      effect of epidural analgesia had worn off, the patient complained of severe pain
      and swelling of the well leg. A diagnosis of well-leg compartment syndrome was
      made and urgent two-incision fasciotomy was performed. CONCLUSION: Obesity and
      prolonged surgery could have caused the acute compartment syndrome of the well
      leg in this patient.

PMID- 24335076
TI  - Community-Based Case Management, Hospital Utilization, and Patient-Focused
      Outcomes in Medicare Beneficiaries.
AB  - There is limited research about the impact of community-based case management
      (CBCM) services and its outcomes with longitudinal analysis. The purpose of this
      study was to evaluate the effectiveness of a CBCM intervention on patient
      outcomes in Medicare beneficiaries with chronic illness in a CBCM service in the
      rural Midwest. A descriptive, repeated-measures design was used, and a secondary
      analysis of a data set containing longitudinal CBCM data, originally collected
      from 2002 to 2007, was conducted. Two years of case management (CM)
      interventions, three health-service utilization outcomes, and three patient
      focused outcomes were examined. The study findings showed that a CBCM had
      significant effect on reducing patients' number of hospitalizations and
      increasing patients' symptom control and quality of life. The impact of CM on
      length of stay and emergency department visits was indeterminate. Findings
      suggest that CBCM can be used as an effective intervention program for Medicare
      beneficiaries. 

PMID- 24335072
TI  - Dry age-related macular degeneration: mechanisms, therapeutic targets, and
      imaging.
AB  - Age-related macular degeneration is the leading cause of irreversible visual
      dysfunction in individuals over 65 in Western Society. Patients with AMD are
      classified as having early stage disease (early AMD), in which visual function is
      affected, or late AMD (generally characterized as either "wet" neovascular AMD,
      "dry" atrophic AMD or both), in which central vision is severely compromised or
      lost. Until recently, there have been no therapies available to treat the
      disorder(s). Now, the most common wet form of late-stage AMD, choroidal
      neovascularization, generally responds to treatment with anti-vascular
      endothelial growth factor therapies. Nevertheless, there are no current therapies
      to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation
      with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant
      vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk
      of progression to advanced AMD, although the impact was in neovascular rather
      than atrophic AMD. Recent findings, however, have demonstrated several features
      of early AMD that are likely to be druggable targets for treatment. Studies have
      established that much of the genetic risk for AMD is associated with complement
      genes. Consequently, several complement-based therapeutic treatment approaches
      are being pursued. Potential treatment strategies against AMD deposit formation
      and protein and/or lipid deposition will be discussed, including anti-amyloid
      therapies. In addition, the role of autophagy in AMD and prevention of oxidative
      stress through modulation of the antioxidant system will be explored. Finally,
      the success of these new therapies in clinical trials and beyond relies on early
      detection, disease typing, and predicting disease progression, areas that are
      currently being rapidly transformed by improving imaging modalities and
      functional assays.

PMID- 24335077
TI  - Cardiac morphology and performance in severe obesity: size really does matter.

PMID- 24335078
TI  - Much work still to be done to prevent central line-associated bloodstream
      infections.

PMID- 24335079
TI  - Early results of endoscopic treatment of vesicoureteral reflux with polyacrylate
      polyalcohol copolymer.
AB  - OBJECTIVE: To evaluate the early results of endoscopic treatment of
      vesicoureteral reflux (VUR) in children using polyacrylate polyalcohol copolymer
      (PPC). PATIENTS AND METHODS: We retrospectively reviewed 45 patients treated with
      subureteric injection of PPC in our clinic. The results of voiding
      cystouretrography performed on the 3rd postoperative month and the results of 1
      year follow-up were evaluated. RESULTS: A total of 45 patients (57 ureters)
      underwent injection of PPC. The mean age of the patients was 6.5 years. There
      were 6 (10.5%) grade 1, 7 (12.2%) grade 2, 26 (45.6%) grade 3, 16 (28%) grade 4,
      and 2 (3.5%) grade 5 VUR. There were 11 overactive bladders, 2 duplex collecting
      systems, and 4 posterior urethral valves among the patients. Voiding
      cystouretrography postoperatively at the 3rd month showed that VUR had
      disappeared in 82.5% (47/57) of the ureters, downgraded to grade 2 and 3 in 7%
      (4/57), persisted in 5.2% (3/57) and upgraded in 5.2% (3/57). The success rate at
      the end of the first year was 98.1%. The procedure was free of complications such
      as fever, dysuria, lumbar pain or obstruction in all patients. No patient showed
      VUR recurrence at the end of the first year. CONCLUSIONS: The short-term results
      of our patients suggested that PPC can be safely and successfully used in the
      endoscopic treatment of VUR in children. However, further prospective, controlled
      trials showing the long-term results of the patients are needed.

PMID- 24335080
TI  - Bioinformatic analysis of the protein/DNA interface.
AB  - To investigate the principles driving recognition between proteins and DNA, we
      analyzed more than thousand crystal structures of protein/DNA complexes. We
      classified protein and DNA conformations by structural alphabets, protein blocks
      [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for
      predicting backbone structures in terms of protein blocks. Prots. Struct. Funct.
      Genet., 41:271-287)] and dinucleotide conformers [Svozil, Kalina, Omelka and
      Schneider (2008) (DNA conformations and their sequence preferences. Nucleic Acids
      Res., 36:3690-3706)], respectively. Assembling the mutually interacting protein
      blocks and dinucleotide conformers into 'interaction matrices' revealed their
      correlations and conformer preferences at the interface relative to their
      occurrence outside the interface. The analyzed data demonstrated important
      differences between complexes of various types of proteins such as transcription
      factors and nucleases, distinct interaction patterns for the DNA minor groove
      relative to the major groove and phosphate and importance of water-mediated
      contacts. Water molecules mediate proportionally the largest number of contacts
      in the minor groove and form the largest proportion of contacts in complexes of
      transcription factors. The generally known induction of A-DNA forms by
      complexation was more accurately attributed to A-like and intermediate A/B
      conformers rare in naked DNA molecules. 

PMID- 24335081
TI  - Evidence for G-quadruplex in the promoter of vegfr-2 and its targeting to inhibit
      tumor angiogenesis.
AB  - Tumor angiogenesis is mainly mediated by vascular endothelial growth factor
      (VEGF), a pro-angiogenic factor produced by cancer cells and active on the
      endothelium through the VEGF receptor 2 (VEGFR-2). Here we identify a G-rich
      sequence within the proximal promoter region of vegfr-2, able to form an
      antiparallel G-quadruplex (G4) structure. This G4 structure can be efficiently
      stabilized by small molecules with the consequent inhibition of vegfr-2
      expression. Functionally, the G4-mediated reduction of VEGFR-2 protein causes a
      switching off of signaling components that, converging on actin cytoskeleton,
      regulate the cellular events leading to endothelial cell proliferation, migration
      and differentiation. As a result of endothelial cell function impairment,
      angiogenic process is strongly inhibited by G4 ligands both in vitro and in vivo.
      Interestingly, the G4-mediated antiangiogenic effect seems to recapitulate that
      observed by using a specific interference RNA against vegfr-2, and it is strongly
      antagonized by overexpressing the vegfr-2 gene. In conclusion, we describe the
      evidence for the existence of G4 in the promoter of vegfr-2, whose expression and
      function can be markedly inhibited by G4 ligands, thereby revealing a new, and so
      far undescribed, way to block VEGFR-2 as target for anticancer therapy. 

PMID- 24335082
TI  - Small RNAs reveal two target sites of the RNA-maturation factor Mbb1 in the
      chloroplast of Chlamydomonas.
AB  - Many chloroplast transcripts are protected against exonucleolytic degradation by
      RNA-binding proteins. Such interactions can lead to the accumulation of short
      RNAs (sRNAs) that represent footprints of the protein partner. By mining existing
      data sets of Chlamydomonas reinhardtii small RNAs, we identify chloroplast sRNAs.
      Two of these correspond to the 5'-ends of the mature psbB and psbH messenger RNAs
      (mRNAs), which are both stabilized by the nucleus-encoded protein Mbb1, a member
      of the tetratricopeptide repeat family. Accordingly, we find that the two sRNAs
      are absent from the mbb1 mutant. Using chloroplast transformation and site
      directed mutagenesis to survey the psbB 5' UTR, we identify a cis-acting element
      that is essential for mRNA accumulation. This sequence is also found in the 5'
      UTR of psbH, where it plays a role in RNA processing. The two sRNAs are centered
      on these cis-acting elements. Furthermore, RNA binding assays in vitro show that
      Mbb1 associates with the two elements specifically. Taken together, our data
      identify a conserved cis-acting element at the extremity of the psbH and psbB 5'
      UTRs that plays a role in the processing and stability of the respective mRNAs
      through interactions with the tetratricopeptide repeat protein Mbb1 and leads to
      the accumulation of protected sRNAs. 

PMID- 24335083
TI  - Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the
      m3U methylations of 25S rRNA in Saccharomyces cerevisiae.
AB  - RNA contains various chemical modifications that expand its otherwise limited
      repertoire to mediate complex processes like translation and gene regulation. 25S
      rRNA of the large subunit of ribosome contains eight base methylations. Except
      for the methylation of uridine residues, methyltransferases for all other known
      base methylations have been recently identified. Here we report the
      identification of BMT5 (YIL096C) and BMT6 (YLR063W), two previously
      uncharacterized genes, to be responsible for m3U2634 and m3U2843 methylation of
      the 25S rRNA, respectively. These genes were identified by RP-HPLC screening of
      all deletion mutants of putative RNA methyltransferases and were confirmed by
      gene complementation and phenotypic characterization. Both proteins belong to
      Rossmann-fold-like methyltransferases and the point mutations in the S-adenosyl-L
      methionine binding pocket abolish the methylation reaction. Bmt5 localizes in the
      nucleolus, whereas Bmt6 is localized predominantly in the cytoplasm. Furthermore,
      we showed that 25S rRNA of yeast does not contain any m5U residues as previously
      predicted. With Bmt5 and Bmt6, all base methyltransferases of the 25S rRNA have
      been identified. This will facilitate the analyses of the significance of these
      modifications in ribosome function and cellular physiology.

PMID- 24335084
TI  - Structure and sequence elements of the CR4/5 domain of medaka telomerase RNA
      important for telomerase function.
AB  - Telomerase is a unique reverse transcriptase that maintains the 3' ends of
      eukaryotic chromosomes by adding tandem telomeric repeats. The RNA subunit (TR)
      of vertebrate telomerase provides a template for reverse transcription, contained
      within the conserved template/pseudoknot domain, and a conserved regions 4 and 5
      (CR4/5) domain, all essential for catalytic activity. We report the nuclear
      magnetic resonance (NMR) solution structure of the full-length CR4/5 domain from
      the teleost fish medaka (Oryzias latipes). Three helices emanate from a
      structured internal loop, forming a Y-shaped structure, where helix P6 stacks on
      P5 and helix P6.1 points away from P6. The relative orientations of the three
      helices are Mg2+ dependent and dynamic. Although the three-way junction is
      structured and has unexpected base pairs, telomerase activity assays with
      nucleotide substitutions and deletions in CR4/5 indicate that none of these are
      essential for activity. The results suggest that the junction is likely to change
      conformation in complex with telomerase reverse transcriptase and that it
      provides a flexible scaffold that allows P6 and P6.1 to correctly fold and
      interact with telomerase reverse transcriptase.

PMID- 24335087
TI  - Factors associated with delayed diagnosis of breast cancer in northeast Thailand.
AB  - BACKGROUND: We identified factors associated with delayed first consultation for
      breast symptoms (patient delay), delayed diagnosis after first consultation
      (doctor delay), and advanced pathologic stage at presentation among 180 women
      with breast cancer in Thailand. METHODS: In this cross-sectional study 180
      patients with invasive breast cancer were interviewed about potential risk
      factors and markers of delayed presentation. Patient delay was defined as time
      from onset of symptoms to first consultation with a health care provider, and
      doctor delay was defined as time from first consultation with a health care
      provider to diagnosis of breast cancer. Linear regression and logistic regression
      were used for the data analyses. RESULTS: Among the 180 patients, 17% delayed
      seeking consultation for longer than 3 months, and 42% reported a doctor delay of
      longer than 3 months. In multivariate linear analysis, a significant increase in
      patient delay was associated with higher family income and smoking; factors
      associated with increased doctor delay were previous breast symptoms, self
      treatment, and travel time to the hospital. In multiple logistic regression,
      doctor delay was related to age at first birth (P = 0.003), previous breast
      symptoms (P = 0.01), and number of consultations with a surgeon before diagnosis
      (P = 0.007). Regarding stage of breast cancer, there were significant
      associations with age at diagnosis (P for trend = 0.04), education (P for trend =
      0.01), family income (P for trend = 0.02), time to referral (P = 0.01), and
      number of consultations with a surgeon before diagnosis (P < 0.01). CONCLUSIONS:
      Hospital referral from a health care provider was a major contributor to delayed
      diagnosis. Breast cancer awareness campaigns in Thailand should target
      individuals in low- and high-income groups, as well as practitioners.

PMID- 24335086
TI  - Effect of maternal smoking cessation before and during early pregnancy on fetal
      and childhood growth.
AB  - BACKGROUND: Maternal smoking during pregnancy is a major cause of intrauterine
      growth restriction and childhood obesity, but only a few studies have examined
      the association of smoking cessation before and during pregnancy with fetal and
      childhood growth. We examined this association in a prospective cohort study in
      Japan. METHODS: Our study included children born between 1991 and 2006 and their
      mothers. Using a questionnaire, maternal smoking status was recorded at
      pregnancy. The anthropometric data of the children were collected during a
      medical check-up at age 3 years. Multiple linear and logistic regression models
      were used for data analysis stratified by sex. RESULTS: In total, 2663 mothers
      reported their smoking status during early pregnancy, and data were collected
      from 2230 (83.7%) children at age 3 years. Maternal smoking during pregnancy was
      associated with a significant reduction in birth weight (approximately 120-150
      g). Body mass index at age 3 years was significantly higher among boys born to
      smoking mothers than among boys born to nonsmoking mothers. Maternal smoking
      during pregnancy was associated with overweight at age 3 years among boys
      (adjusted odds ratio, 2.4; 95% CI, 1.03-5.4). However, among women who stopped
      smoking in early pregnancy, there was no increase in the risks of a small for
      gestational age birth or childhood overweight at age 3 years. CONCLUSIONS:
      Children born to mothers who stopped smoking before or during early pregnancy had
      appropriate fetal and childhood growth.

PMID- 24335085
TI  - Structure of the mammalian ribosomal pre-termination complex associated with
      eRF1.eRF3.GDPNP.
AB  - Eukaryotic translation termination results from the complex functional interplay
      between two release factors, eRF1 and eRF3, in which GTP hydrolysis by eRF3
      couples codon recognition with peptidyl-tRNA hydrolysis by eRF1. Here, we present
      a cryo-electron microscopy structure of pre-termination complexes associated with
      eRF1*eRF3*GDPNP at 9.7 -A resolution, which corresponds to the initial pre-GTP
      hydrolysis stage of factor attachment and stop codon recognition. It reveals the
      ribosomal positions of eRFs and provides insights into the mechanisms of stop
      codon recognition and triggering of eRF3's GTPase activity. 

PMID- 24335088
TI  - Kmasker--a tool for in silico prediction of single-copy FISH probes for the large
      genome species Hordeum vulgare.
AB  - Specific localization of large genomic fragments by fluorescence in situ
      hybridization (FISH) is challenging in large- genome plant species due to the
      high content of repetitive sequences. We report the automated work flow (Kmasker)
      for in silico extraction of unique genomic sequences of large genomic fragments
      suitable for FISH in barley. This method can be widely used for the integration
      of genetic and cytogenetic maps in plants and other species with large and
      complex genomes if the probe sequence (e.g. BACs, sequence contigs) and a low
      coverage (8-fold) of unassembled sequences of the species of interest are
      available. Kmasker has been made publicly available as a web tool at
      http://webblast.ipk-gatersleben.de/kmasker.

PMID- 24335089
TI  - Penile Mondor's syndrome after endovenous treatment of the great saphenous vein
      with 1470 nm diode laser.
AB  - We report a penile Mondor's disease after endovenous laser ablation with a 1470
      nm diode laser of the great saphenous vein with additional foam sclerotherapy of
      distal tributaries. We administered body-weight adjusted full dose of low
      molecular weight heparin (enoxaparin) in a therapeutic dosage for 10 days. In
      addition, anti-inflammatory therapy with diclofenac-sodium 75 mg twice a day for
      the following five days was initiated. One month later, the patient reported no
      further discomfort or pain and the thrombophlebitis of the superficial dorsal
      penile vein had sonographically disappeared completely.

PMID- 24335090
TI  - Treatment of severe chronic venous insufficiency with ultrasound-guided foam
      sclerotherapy: a two-year series in a single center in Brazil.
AB  - OBJECTIVES: To portray the initial experience at a public health center of the
      Federal District of Brazil in the treatment of chronic venous insufficiency with
      ultrasound-guided foam sclerotherapy in patients in advanced stages of the
      disease. METHOD: Eighty-seven reports of patients in C5 and C6 stages, according
      to CEAP classification, were evaluated for clinical improvements, ulcer-healing
      rates, and complications of ultrasound-guided foam sclerotherapy. McNemar test
      was used for statistical analysis with the level of significance set at 5% (P
      value, 0.05). RESULTS: The results showed high rates of ulcer healing (85%) and
      significant improvement of symptoms after treatment, such as pain, heaviness,
      fatigue, burning, paresthesia, and itching (P < 0.0001). CONCLUSIONS: An
      outpatient, low-cost and high-resolution technique, without the need for
      hospitalization and use of the operating room showed to be a safe and effective
      alternative for the treatment of varicose disease associated with severe chronic
      venous insufficiency.

PMID- 24335091
TI  - Floating left innominate vein neoplastic thrombus: a rare case of mediastinal
      extension of follicular thyroid carcinoma.
AB  - OBJECTIVE: We report a case of advanced follicular thyroid cancer with innominate
      vein involvement. To our knowledge, this seems to be the first case treated in
      emergency surgery, reported in literature. METHOD: A 59-year-old woman with a
      five-year history of a large and mainly right-sided cervical mass presented with
      dyspnea, unilateral arm swelling, facial flushing, and venous congestion. An
      emergency computed tomography scan revealed a thyroid mass extending into the
      upper mediastinum with displacement and compression of the right jugular vein and
      carotid artery and apparent adherence to the superior vena cava and left
      innominate vein. RESULTS: An emergency total thyroidectomy was performed by means
      of a sternotomy. The lower portion of the retrosternal goiter projected directly
      into the left innominate vein, with tumor floating in its lumen. Removal of the
      neoplastic thrombus was performed, through an incision in the vein, en bloc with
      the thyroid mass. Both goiter and thrombus were completely replaced by follicular
      carcinoma. CONCLUSIONS: Accurate preoperative assessment through contrast
      enhanced computed tomography is strongly suggested in the presence of enlarged
      thyroid gland extending into the mediastinum whenever angioinvasion is suspected.
      This could prevent blinded maneuvers such as digital externalization of the
      thoracic component of the gland, which can be fatal in cases of cervico
      mediastinal goiter extending into great cervical or mediastinal veins.

PMID- 24335092
TI  - CCDC62 variant rs12817488 is associated with the risk of Parkinson's disease in a
      Han Chinese population.
AB  - It has been recently proposed by a genome-wide association study (GWAS) meta
      analysis that the CCDC62 variant rs12817488 is a new risk locus associated with
      Parkinson's disease (PD). In this study, we aimed to investigate the association
      between rs12817488 and PD in a Chinese cohort. A total of 341 PD patients and 423
      matched controls were recruited in Eastern China. Our results showed that the A
      allele of rs12817488 was significantly associated with an aggravated risk of PD
      (p = 0.006) and represented a major allele in contrast to a minor one in
      Caucasians. Genotype distributions also differed between PD patients and controls
      (p = 0.011 for AA/AG/GG). Further analysis showed that the association of
      rs12817488 with PD only existed in females. We also investigated the protein
      level of CCDC62 in peripheral blood mononuclear cells from 41 AA or GG carriers
      and found an apparently higher expression in PD patients carrying the AA
      genotype. A potential interaction was found between two estrogen-related loci,
      i.e. rs12817488/CCDC62 and rs2697962/PRDM2, particularly in the female stratum.
      In conclusion, our study demonstrated for the first time a significant
      association between the rs12817488 polymorphism and PD predisposition in a
      Chinese population with gender variations and provides new insight regarding the
      variant's protein expression and estrogen-related genetic interaction.

PMID- 24335093
TI  - Correlation discrepancies between high-grade squamous intraepithelial lesions and
      high-grade cervical intraepithelial neoplasia: a cytological/histological
      correlation study from a single-institution experience.
AB  - OBJECTIVE: Previous studies have demonstrated diagnostic discrepancies for the
      detection of high-grade cervical intraepithelial neoplasia (CIN 2/3) from
      previously confirmed cytological high-grade squamous intraepithelial lesions
      (HSILs). The goal of this study is to investigate the possible factors which may
      be responsible for this diagnostic discrepancy. STUDY DESIGN: The study included
      all the cytological specimens diagnosed with a HSIL by the Papanicolaou (Pap)
      test at Temple University Hospital (2000-2010) as well as timely follow-up
      cervical biopsies. The biopsy tissue types and diagnoses were subsequently
      categorized and analyzed. RESULTS: Of the total 842 Pap tests with HSIL
      diagnosis, 96 cases (11.4%) showed non-CIN 2/3 in follow-up cervical biopsies.
      Among those cases, the most common biopsy diagnoses were cervicitis (27.9%) and
      CIN 1 (25%). Endocervical curettage (ECC) samples showed a high percentage of
      inadequacy for diagnosis (43.7%). Thirty-seven cases had subsequent follow-up
      biopsy, and CIN 2/3 was found in 15 cases. However, none of the CIN 2/3 cases was
      detected by ECC sampling. CONCLUSIONS: Our study indicated that the discrepant
      correlation between HSIL and CIN 2/3 was most likely due to tissue sampling
      issues during colposcopic examination. The diagnostic value of ECC remains poor
      for the detection and grading of cervical intraepithelial dysplasia.

PMID- 24335094
TI  - Induction of the connexin 32 gene by epigallocatechin-3-gallate potentiates
      vinblastine-induced cytotoxicity in human renal carcinoma cells.
AB  - BACKGROUND/AIM: Enforced expression of the connexin (Cx) 32 gene, a member of the
      gap junction gene family and a tumor suppressor gene in human renal cell
      carcinoma (RCC), enhanced vinblastine (VBL)-induced cytotoxicity in RCC cells due
      to suppression of multidrug resistance 1 (MDR1) expression. Furthermore, in RCC
      the Cx32 gene is silenced by hypermethylation of CpG islands in a promoter region
      of the Cx gene. In this study, we investigated if the green tea polyphenol
      epigallocatechin-3-gallate (EGCG) could enhance susceptibility of RCC cells (Caki
      1, a human metastatic RCC cell) to VBL. METHODS: The effects of EGCG on Caki-1
      cells were estimated by WST-1 (cell viability), real-time RT-PCR (mRNA level) and
      immunoblotting (protein level). We estimated the methylation status in the
      promoter region of the Cx32 gene in RCC cells by methylation-specific PCR. Each
      protein function was inhibited by small interfering RNA (siRNA) and specific
      inhibitors. RESULTS: The EGCG treatment elicited significant upregulation of Cx32
      in Caki-1 cells, and the induction of the Cx led to the suppression of MDR1 mRNA
      expression through inactivation of Src and subsequent activation of c-Jun NH2
      terminal kinase (JNK). Chemical sensitivity to VBL in Caki-1 cells was increased
      by EGCG pretreatment, and this effect was abrogated by siRNA-mediated knockdown
      of Cx32. CONCLUSION: This study suggests that the restoration of Cx32 by EGCG
      pretreatment improves chemical tolerance on VBL in Caki-1 cells via the
      inactivation of Src and the activation of JNK.

PMID- 24335095
TI  - A tortoiseshell male cat: chromosome analysis and histologic examination of the
      testis.
AB  - Tortoiseshell coat color is normally restricted to female cats due to X-linkage
      of the gene that encodes the orange coat color. Tortoiseshell male cats do,
      however, occur at a low frequency among tortoiseshell cats because of chromosome
      aberrations similar to the Klinefelter syndrome in man: the extra X chromosome of
      a 39,XXY karyotype introduces the possibility of an orange and a non-orange
      allele which produce the mixture of orange and non-orange coat spotting known as
      tortoiseshell. We analyzed the chromosome complement of a fibroblast culture and
      did histological examinations of testicular tissue from a tortoiseshell male cat
      referred to us. Chromosome analysis using RBA-banding consistently revealed a
      39,XXY karyotype. Histological examinations of testis biopsies from this cat
      showed degeneration of the tubules, hyperplasia of the interstitial tissue, and
      complete loss of germ cells. Immunostaining using anti-vimentin and anti-VASA
      (DDX4) showed that only Sertoli cells and no germ cells were observed in the
      testicular tubules. As no sign of spermatogenesis was detected, we conclude that
      this is a classic case of a sterile, male tortoiseshell cat with a 39,XXY
      chromosome complement.

PMID- 24335096
TI  - Beckwith-Wiedemann syndrome: growth pattern and tumor risk according to molecular
      mechanism, and guidelines for tumor surveillance.
AB  - BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome
      associated with an increased risk of pediatric tumors. The underlying molecular
      abnormalities may be genetic (CDKN1C mutations or 11p15 paternal uniparental
      isodisomy, pUPD) or epigenetic (imprinting center region 1, ICR1, gain of
      methylation, ICR1 GOM, or ICR2 loss of methylation, ICR2 LOM). AIM: We aimed to
      describe a cohort of 407 BWS patients with molecular defects of the 11p15 domain
      followed prospectively after molecular diagnosis. RESULTS: Birth weight and
      length were significantly higher in patients with ICR1 GOM than in the other
      groups. ICR2 LOM and CDKN1C mutations were associated with a higher prevalence of
      exomphalos. Mean adult height (regardless of molecular subtype, n = 35) was 1.8
      +/- 1.2 SDS, with 18 patients having a final height above +2 SDS. The prevalence
      of tumors was 8.6% in the whole population; 28.6 and 17.3% of the patients with
      ICR1 GOM (all Wilms tumors) and 11p15 pUPD, respectively, developed a tumor
      during infancy. Conversely, the prevalence of tumors in patients with ICR2 LOM
      and CDKN1C mutations were 3.1 and 8.8%, respectively, with no Wilms tumors.
      CONCLUSION: Based on these results for a large cohort, we formulated guidelines
      for the follow-up of these patients according to the molecular subtype of BWS.

PMID- 24335097
TI  - Cardiac structure and function and insulin resistance in morbidly obese patients:
      does superobesity play an additional role?
AB  - OBJECTIVE: To evaluate the impact of superobesity, defined as body mass index
      (BMI) >=50, on cardiac structure and function. METHODS: Using echocardiography,
      we studied 198 asymptomatic patients (mean age 48 +/- 13 years, 29.3% were men)
      with a BMI >=40. Insulin resistance was measured using the Homeostasis Model
      Assessment of insulin resistance (HOMA-IR). Patients were divided into 2 groups:
      morbidly obese (BMI >=40 and <50; n = 160) and superobese (BMI >=50; n = 38).
      RESULTS: There were no significant differences in age, gender, hypertension and
      diabetes between groups. Superobese patients had higher LV mass (66.0 +/- 14.7
      vs. 59.9 +/- 11.9 g/m(2.7), p = 0.007), left ventricular (LV) end-diastolic (33.8
      +/- 7.7 vs. 31.5 +/- 7.1 ml/m(2.7), p = 0.041) and end-systolic (12.2 +/- 3.6 vs.
      10.9 +/- 2.8 ml/m(2.7), p = 0.016) volumes, left atrial volume (13.8 +/- 4.5 vs.
      12.2 +/- 3.9 ml/m(2.7), p = 0.029), peak velocity of transmitral flow in early
      diastole/early diastolic peak myocardial velocity ratio (9.1 +/- 2.6 vs. 8.2 +/-
      2.2, p = 0.03) and HOMA-IR (9.7 +/- 7.3 vs. 7.3 +/- 6.5, p = 0.047). LV ejection
      fraction was similar. CONCLUSIONS: Superobesity is associated with insulin
      resistance and a worse impact on cardiac remodeling and LV diastolic function
      than morbid obesity. Prospective studies are needed to evaluate whether such
      further classification of morbid obesity could stratify the cardiovascular risk
      in these patients more accurately.

PMID- 24335098
TI  - Safety profile comparison between extemporaneous and a licensed preparation of
      caffeine citrate in preterm infants with apnea of prematurity.
AB  - BACKGROUND: Given the lack of a licensed product (LP), extemporaneous caffeine
      citrate (ECC) has been used by many hospital pharmacies. OBJECTIVES: Since July
      2011, an LP has been available in Germany. We prospectively compared the safety
      profile of ECC and LP in preterm infants with apnea of prematurity. METHODS:
      Between April 2010 and April 2013, selected side effects occurring with ECC or LP
      were documented in 6 German NICUs for infants <=34 weeks' gestation using a
      longitudinal study design. The software developed for daily prescriptions in NICU
      residents requires entries if any of the following symptoms occurred during the
      last 24 h: tachycardia (resting heart rate >200/min), clinical or
      encephalographic seizures, gastric residuals, vomiting, or necrotizing
      enterocolitis (NEC). ECC and LP were administered at identical doses (20
      mg/kg/day loading, 5-10 mg/kg/day maintenance) and in similar formulations either
      orally or intravenously. RESULTS: 562 infants with 14,590 treatment days on ECC
      and 538 infants with 12,813 treatment days on LP were evaluated. The mean
      gestational age was similar (29.20 weeks for ECC vs. 29.14 weeks for LP). No
      relevant differences were seen concerning tachycardia, gastric residuals, or
      vomiting, but ECC was associated with a higher risk of NEC (risk ratio: 2.68, 95%
      CI: 1.01-7.23, p = 0.047) and, albeit not significantly so, seizures (risk ratio:
      1.91, 95% CI: 0.53-6.96, p = 0.35). CONCLUSION: This survey demonstrates a
      similar safety profile for both forms of caffeine citrate. The lower NEC and
      seizure rate seen with the LP is intriguing, but requires confirmation in a
      controlled study design.

PMID- 24335099
TI  - Trastuzumab beyond progression in advanced breast cancer: national guidance
      versus oncologist's decision.

PMID- 24335100
TI  - Exhaled breath temperature in asthmatics and controls after eucapnic voluntary
      hyperventilation and a methacholine challenge test.
AB  - BACKGROUND: It has been suggested that exhaled breath temperature (EBT) is
      increased in asthmatic subjects. OBJECTIVES: Our aim was to investigate EBT in
      asthmatics compared to healthy controls before and after eucapnic voluntary
      hyperventilation (EVH) and a methacholine challenge test (MCT). METHODS: A total
      of 26 asthmatics and 29 healthy controls were included. Forced expiratory volume
      in 1 s (FEV1), EBT and oral, axillary and auricular temperatures were measured
      before and after EVH and MCT. RESULTS: FEV1 % predicted (%p) was significantly
      lower in asthmatic subjects compared to healthy controls at all time points. EBT
      was significantly increased in all subjects 15-30 min after EVH and 5-45 min
      after MCT. Oral temperature displayed a similar pattern of increase, in contrast
      to axillary and auricular temperature, and correlated with EBT before and after
      both of the challenge tests. EBT after 5 min correlated with the largest drop in
      FEV1%p after EVH in asthmatic subjects. No significant differences or changes in
      EBT were found when comparing asthmatics to healthy controls before or after any
      of the tests. CONCLUSIONS: EBT is increased after both EVH and MCT, possibly
      reflecting a vascular response. This is related to both the fall in FEV1 and to
      oral temperature, suggesting an effect on the whole respiratory tract including
      the oral cavity. No differences in EBT are seen between asthmatics and healthy
      controls, indicating that the increase in EBT is mainly physiological rather than
      pathophysiological.

PMID- 24335101
TI  - Transcranial brain photoplethysmography to study the venules of cerebral cortex
      in patients with multiple sclerosis.
AB  - OBJECTIVE: To evaluate the utility of a transcranial brain photoplethysmography
      parameter as a potential marker for patients with multiple sclerosis. METHODS: We
      investigated 38 patients affected by multiple sclerosis, according to the revised
      McDonald criteria (12 males and 26 females, mean age 41.1 +/- 8.5 years, Expanded
      Disability Status Scale mean value 2.6 +/- 2.1) and compared them with 20 age-
      and sex-matched healthy controls. By means of transcranial brain
      photoplethysmography, a safe and non-invasive technology, we measured the
      increase in cerebral blood volume during compression for 10 s of the internal
      jugular veins of both sides in sitting position. RESULTS: The cerebral blood
      volume increase was significantly smaller in the multiple sclerosis patients
      (left frontal cortex: -58%, p < 0.0001; right frontal cortex: -59%, p < 0.0001)
      compared with the controls. CONCLUSIONS: Our study reveals that a minor increase
      in cerebral blood volume on the frontal cortex of both sides in sitting position
      is associated with a diagnosis of multiple sclerosis and might be a new marker.

PMID- 24335102
TI  - Evolutionary transitions between sex-determining mechanisms: a review of theory.
AB  - The extraordinary diversity of sex-determining mechanisms found in nature is
      thought to have arisen by the addition, modification or replacement of regulators
      at the upstream end of the sex-determining pathway. The spread of a novel
      regulator of sex determination can manifest itself by an evolutionary transition
      between environmental and genetic sex determination, for example, or between male
      and female heterogamety. Both kinds of transition have occurred frequently in the
      course of evolution. In this paper, various evolutionary forces acting on sex
      determining mutations that can bias transitions in one direction or the other are
      reviewed. Furthermore, the adaptive significance of the main modes of sex
      determination are discussed, and the common principle underlying ultimate
      explanations for environmental sex determination, genetic sex determination and
      maternal control over sex determination in the offspring are highlighted. Most of
      the current theory concentrates on the population-genetic aspects of sex
      determination transitions, using models that do not reflect the developmental
      mechanisms involved in sex determination. However, the increasing availability of
      molecular data creates opportunities for the future development of mechanistic
      models that will further clarify how selection and developmental architecture
      interact to direct the evolution of sex determination genes.

PMID- 24335103
TI  - Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in
      refractory mycosis fungoides and Sezary syndrome.
AB  - A phase 2 multicenter trial was performed to evaluate single-agent lenalidomide
      in advanced, refractory mycosis fungoides/Sezary syndrome. Thirty-two patients
      were enrolled with a median of 6 prior treatment regimens, including a median of
      4 systemic therapies. Patients achieved an overall response rate of 28% (9
      patients), and all were partial responses. Median overall survival was 43 months,
      median progression-free survival was 8 months, and median duration of response
      was 10 months. No grade 4 toxicities occurred. Grade 3 adverse events included
      fatigue (22%), infection (9%), and leukopenia (3%). Patients were frequently
      unable to tolerate the 25-mg starting dose of lenalidomide used in other
      hematologic malignancies due to fatigue, pain, and transient flare reaction (TFR)
      as a contributory factor. TFR appeared to correlate with clinical response, but
      the small sample size limited definitive conclusions, and the underlying
      mechanisms of this reaction are not known. Data from correlative studies on
      peripheral blood samples suggest that the effects of lenalidomide could be
      associated with decreased circulating CD25(+) T cells and CD4(+) T-cell numbers.
      Skin lesions showed a trend for increased CD8, CD25, and FoxP3 expression with
      decreased CD4:CD8 ratio. In conclusion, lenalidomide monotherapy demonstrated
      activity in refractory cutaneous T-cell lymphomas, along with acceptable
      toxicity. This trial was registered at www.clinicaltrials.gov as #NCT00466921. 

PMID- 24335104
TI  - Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single
      agent bortezomib therapy.
AB  - Various translocations and mutations have been identified in myeloma, and certain
      aberrations, such as t(4;14) and del17, are linked with disease prognosis. To
      investigate mutational prevalence in myeloma and associations between mutations
      and patient outcomes, we tested a panel of 41 known oncogenes and tumor
      suppressor genes in tumor samples from 133 relapsed myeloma patients
      participating in phase 2 or 3 clinical trials of bortezomib. DNA mutations were
      identified in 14 genes. BRAF as well as RAS genes were mutated in a large
      proportion of cases (45.9%) and these mutations were mutually exclusive. New
      recurrent mutations were also identified, including in the PDGFRA and JAK3 genes.
      NRAS mutations were associated with a significantly lower response rate to single
      agent bortezomib (7% vs 53% in patients with mutant vs wild-type NRAS, P =
      .00116, Bonferroni-corrected P = .016), as well as shorter time to progression in
      bortezomib-treated patients (P = .0058, Bonferroni-corrected P = .012). However,
      NRAS mutation did not impact outcome in patients treated with high-dose
      dexamethasone. KRAS mutation did not reduce sensitivity to bortezomib or
      dexamethasone. These findings identify a significant clinical impact of NRAS
      mutation in myeloma and demonstrate a clear example of functional differences
      between the KRAS and NRAS oncogenes. 

PMID- 24335105
TI  - Constitutive activation of STAT5A and STAT5B regulates IgM secretion in
      Waldenstrom's macroglobulinemia.
AB  - Activation of the Janus kinase family/signal transducer and activator of
      transcription (JAK/STAT) signaling pathway has been associated with the
      pathogenesis and progression of both solid and hematologic malignancies. We have
      detected constitutive activation of STAT5 in malignant B cells derived from
      patients with Waldenstrom's macroglobulinemia (WM). Although short hairpin RNA
      mediated knockdown of the STAT5A and STAT5B isoforms did not affect cellular
      proliferation, loss of STAT5 significantly decreased immunoglobulin M (IgM)
      secretion. A similar dose-dependent inhibition of IgM secretion was observed when
      WM cell lines were treated with a small molecule inhibitor of STAT5. These data
      suggest that STAT5 is involved in regulating IgM production in WM and that
      inhibition of STAT5 may represent a novel therapeutic strategy for lowering IgM
      levels in WM patients. 

PMID- 24335106
TI  - Early molecular response predicts outcomes in patients with chronic myeloid
      leukemia in chronic phase treated with frontline nilotinib or imatinib.
AB  - We explored the impact of early molecular response (EMR; BCR-ABL <=10% on the
      international scale [BCR-ABL(IS)] at 3 or 6 months) on outcomes in patients with
      newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib
      or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and
      Safety in Clinical Trials-Newly Diagnosed Patients. Patients (n = 846) received
      nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg
      once daily. At 3 months, more patients had EMR failure (ie, BCR-ABL(IS) >10%) on
      imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients
      in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all
      arms, EMR failure was associated with lower rates of molecular response, an
      increased risk of progression, and lower overall survival compared with EMR
      achievement. We also analyzed patient and treatment characteristics associated
      with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm.
      High Sokal risk score was associated with a high rate of EMR failure on imatinib,
      but not on nilotinib. In contrast, reduced dose intensity and dose interruptions
      were strongly associated with EMR failure in nilotinib-treated, but not imatinib
      treated, patients. This study is registered at www.clinicaltrials.gov as
      #NCT00471497. 

PMID- 24335107
TI  - Performance of repetitive alternating elbow movements in Parkinson's disease.
AB  - BACKGROUND: Bradydiadochokinesia is one main clinical symptom in idiopathic
      Parkinson's disease (IPD). The pathogenesis of bradydiadochokinesia is not
      completely clear. METHODS: Fifteen patients with IPD and 15 age-matched healthy
      volunteers had to perform rhythmic alternating flexion and extension movements in
      the elbow joint. The rhythm was provided auditorily by a click tone stimulator.
      Six maneuvers (spatial extents of 48 and 83 degrees  at frequencies of 0.45, 0.75
      and 1.25 Hz) had to be absolved. The potentiometer converted the horizontal
      forearm movements into a variable voltage. RESULTS: The duration of single
      movements varied more significantly in patients than in controls (p < 0.05; Mann
      Whitney U test). Patients executed all conditions more slowly than controls, but
      this difference was only significant at the most difficult condition (83 degrees 
      at 1.25 Hz; p < 0.01). The movement amplitudes or their variability were not
      significantly different at any condition. No parameter correlated significantly
      with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) or
      with the duration of disease. CONCLUSION: An insufficient temporal coordination
      contributes to bradydiadochokinesia in IPD. This deficit occurs independently of
      other parkinsonian cardinal motor symptoms.

PMID- 24335108
TI  - 45,X/46,X,r(Y)/46,X,dic r(Y) karyotype in an azoospermic male: a case report.
AB  - Y chromosome abnormalities are frequently associated with male infertility. Men
      with ring Y chromosomes can present with sexual infantilism, ambiguous genitalia,
      hypospadias, or azoospermia. AZF microdeletions can result in spermatogenic
      defects in such patients. Here, we report an unusual karyotype of
      45,X/46,X,r(Y)/46,X,dic r(Y) in an azoospermic man. However, the reason for this
      patient's azoospermia is not an AZF microdeletion but might be the abnormal
      structure of the r(Y) chromosome, the 45,X cell line, mosaicism of the 3 cell
      lines, or another unknown cause. In such cases, if the couple wishes to
      reproduce, cytogenetic, molecular and fluorescent in situ hybridization
      evaluations should be performed, and preimplantation genetic diagnosis should be
      used together with assisted reproductive technology.

PMID- 24335109
TI  - Antineoplastic effect of WIN 55,212-2, a cannabinoid agonist, in a murine
      xenograft model of gastric cancer.
AB  - BACKGROUND: We have previously reported the antineoplastic effects of a
      cannabinoid agonist in gastric cancer cells. Our aim was to evaluate this in a
      murine xenograft model. METHODS: Animal models were created after injecting AGS
      gastric cancer cells subcutaneously into the flank of male BALB/c-nude mice. A
      cannabinoid agonist, WIN 55,212-2 (7 mg/kg body weight) or vehicle was injected
      around the tumor subcutaneously every 24 h for 14 days. Tumors were explanted for
      analysis. RESULTS: Tumor volume decreased by 30% in the WIN 55,212-2-treated
      group compared to the group treated with vehicle (p < 0.05). Apoptotic cells were
      found more commonly in the WIN 55,212-2 treatment group than in the control on
      immunohistochemistry. Compared to the control, WIN 55,212-2 treatment
      significantly increased caspase-3 cleavage and decreased MMP-2, MMP-7 and MMP-9
      protein levels significantly (all p < 0.05). VEGF-A protein level was not
      different between the 2 groups. CONCLUSION: WIN 55,212-2 has antineoplastic
      effect on the gastric cancers in in vivo model.

PMID- 24335110
TI  - Association between serum vitamin D status and functional mobility in memory
      clinic patients aged 65 years and older.
AB  - BACKGROUND: Recent studies have shown that vitamin D status may be relevant for
      physical and cognitive performance in the older population. This association may
      be of particular interest to older people at risk for cognitive impairment and
      functional decline. OBJECTIVE: The aim of this study was to determine the
      association between serum 25-hydroxyvitamin D [25(OH)D] status and functional
      mobility in seniors assessed in a memory clinic. METHODS: We conducted a cross
      sectional study of outpatients (n = 404) in a memory clinic. Functional mobility
      was assessed with three endpoints: normal and fast walking speed and the Timed Up
      and Go (TUG) test. Adjusted multivariate analyses in all patients and two pre
      planned subgroup analyses in vulnerable seniors (previous fall and MMSE score of
      >=26 or no previous fall and MMSE score of <26) versus less vulnerable seniors
      (no previous fall and MMSE score of >=26) were performed to assess the
      association of 25(OH)D and functional mobility. RESULTS: Overall, mean 25(OH)D
      serum levels were 63.2 +/- 33.9 nmol/l, and 41.3% were vitamin D deficient (<50
      nmol/l). Seniors in the lowest 25(OH)D quartile (<39 nmol/l) had significantly
      worse functional mobility compared to the highest 25(OH)D quartile (>81 nmol/l);
      adjusted for all covariates, seniors in the highest quartile performed 9.4%
      better in normal (p = 0.02) and 9.2% better in fast (p = 0.004) walking speed,
      and 4.4% better in the TUG test (p = 0.24). The association between 25(OH)D
      status and functional mobility was most pronounced in less vulnerable seniors (p
      for trend significant for all three mobility tests). Seniors with a higher
      25(OH)D status also had better cognitive function (MMSE score; p = 0.006).
      CONCLUSIONS: Lower serum 25(OH)D status is associated with poorer functional
      mobility and cognitive function, therefore supporting 25(OH)D assessment in this
      population at risk for both functional and cognitive decline.

PMID- 24335113
TI  - Is rosiglitazone as safe as BARI 2D and the reanalysis of RECORD imply?

PMID- 24335114
TI  - 'I'm really glad this is developmental': autism and social comparisons - an
      interpretative phenomenological analysis.
AB  - The present qualitative study comprised interviews with nine young people with
      autism (aged 16-21 years) about their perceptions of autism. Using interpretative
      phenomenological analysis, three underlying themes were illuminated, and all
      these formed the superordinate theme Making Comparisons: (a) Changes over time:
      'I'm really glad this is developmental'; (b) Degrees of autism: 'They've got it
      really bad'; and (c) Degrees of ability: 'I'm not really disabled-disabled'. Such
      comparisons were not explicitly sought at the outset of the study, and instead
      emerged from their conceptualisations of the autism concept. When comparing how
      they perceived themselves now, and how they perceived themselves in the past, the
      young people viewed themselves more positively in the present. In addition, when
      making comparisons with other people with autism, they tended to locate
      themselves as being in a better position than others were. The perspective of
      being in a more fortunate position because of heightened abilities also emerged
      from the comparisons made with people who did not have autism. Furthermore,
      similar comparisons were made when autism was compared to disability, with autism
      being evaluated as being more favourable than what was termed 'proper'
      disability. The results of this study are discussed in relation to the existent
      social comparison literature. 

PMID- 24335115
TI  - The role of emotion perception in adaptive functioning of people with autism
      spectrum disorders.
AB  - Cognitive functioning has historically been used to predict adaptive outcomes of
      people with autism spectrum disorders; however, research shows that it is not a
      complete predictor. The current study explored whether emotion perception was a
      predictor of adaptive outcomes, and more specifically, hypothesized that emotion
      perception (Diagnostic Analysis of Nonverbal Accuracy-2 error scores) would
      mediate adaptive functioning of people with autism spectrum disorder (Vineland
      Adaptive Behavior Scales, Second Edition). People with autism spectrum disorders
      demonstrated significantly lower adaptive functioning and emotion perception
      skills compared to typically developing individuals. Emotion perception acted as
      a significant mediator for socialization, but not communication or daily living
      skills, highlighting that in people with autism spectrum disorders, lower
      socialization abilities is the result, in part, of emotion perception deficits.
      It was unexpected that emotion perception was not a mediator for communication
      skills. This may be related to sample restrictions, or the narrow focus on
      emotion perception. Future research should involve a larger, more inclusive
      autism spectrum disorder sample, broaden approaches to exploring relationships
      between social perception and adaptive outcomes, and relate findings to brain
      mechanisms underlying emotion perception. 

PMID- 24335116
TI  - Reduced delay of gratification and effortful control among young children with
      autism spectrum disorders.
AB  - We explored internal control of behavior using direct observation and parent
      report. Previous research has found that both the delay of gratification task and
      parent-reported effortful control predict later social ability and more positive
      outcomes in typically developing children. Children with autism spectrum disorder
      have previously been reported to have reduced effortful control, whereas delay of
      gratification ability has not been tested in a group with autism spectrum
      disorder. The current study compared 21 children with autism spectrum disorder
      and 21 typically developing children between 6 and 7 years of age-all of whom had
      cognitive ability at or above the average range. Children with autism spectrum
      disorder were less able to delay gratification, and their parents reported
      significantly reduced effortful control; however, scores on these measures were
      unrelated within the group with autism spectrum disorder. Among the children with
      autism spectrum disorder, lower effortful control was associated with more severe
      clinician-observed social symptoms. 

PMID- 24335117
TI  - Epidemiology, meta-analysis, and macro-economics.

PMID- 24335118
TI  - Crystal-clear water transport.

PMID- 24335119
TI  - Catheter-related peritonitis.

PMID- 24335120
TI  - The possible impact of the US prospective payment system ("bundle") on the growth
      of peritoneal dialysis.

PMID- 24335121
TI  - Dialysis modality after renal transplant failure.

PMID- 24335122
TI  - A qualitative systematic review of the literature supporting a causal
      relationship between exit-site infection and subsequent peritonitis in patients
      with end-stage renal disease treated with peritoneal dialysis.
AB  - OBJECTIVE: The objective of our research was to summarize and review evidence
      supporting a causal relationship between exit-site infection and peritonitis in
      peritoneal dialysis (PD) patients. DATA SOURCES: We undertook a qualitative
      review of studies retrieved from MEDLINE, EMBASE, and PubMed, and supplemented
      that process with a hand search of references and abstracts in the literature.
      STUDY SELECTION: Our quality criteria were based on the Paediatric Risk of
      Mortality guidelines, definitions, and recommendations from the International
      Society for Peritoneal Dialysis (ISPD), and the Bradford Hill criteria for
      causality. All identified abstracts were reviewed for content. Of 776 abstracts,
      59 were selected for full-text evaluation, and 22 of those met the ISPD criteria
      for good-quality research in PD-related infections. Of the 22 eligible studies, 9
      met the study's quality criteria and were included in the summative analysis. No
      articles reported sufficient data for a quantitative analysis. DATA EXTRACTION:
      Information on study design, study population characteristics, definitions,
      peritonitis rates, exit-site care protocol, exit-site treatment protocol, follow
      up period, potential bias, and outcomes was extracted. Criteria for including
      data in the final study were determined using ISPD guidelines. DATA SYNTHESIS: Of
      the 9 included studies, 8 suggested that a history of exit-site infection
      increased the risk for subsequent peritonitis. Of those studies, 3 met 5
      causality criteria, 4 met 4 causality criteria, and 1 met 3 causality criteria.
      CONCLUSIONS: The literature provides weak evidence to support a causal
      relationship between exit-site infection and subsequent peritonitis. Few criteria
      for causation were met. We were unable to attribute causation and could assume an
      association only. The exclusion of studies focusing on PD-related tunnel
      infections may be viewed as both a strength and a limitation of the present work.

PMID- 24335123
TI  - Infrastructure requirements for an urgent-start peritoneal dialysis program.
AB  - Patients with advanced chronic kidney disease nearing dialysis but without pre
      established access almost uniformly initiate dialysis with a temporary central
      venous catheter. These catheters are associated with high rates of infection and
      flow disturbances, requiring removal and subsequent replacement. Many of these
      patients might be candidates for peritoneal dialysis (PD), but because of the
      absence of prior catheter placement, the default initial modality is
      hemodialysis. Recent reports, however, have demonstrated the feasibility of
      initiating PD urgently despite the late referral for access placement. Urgent
      start PD clinical pathways require a unique infrastructure and treatment
      approach. This article reviews the salient features required to establish an
      urgent-start PD program. 

PMID- 24335124
TI  - Metabolic implications of peritoneal dialysis in patients with acute kidney
      injury.
AB  - BACKGROUND: Peritoneal dialysis (PD) is a treatment for selected acute kidney
      injury patients (AKI), but little is known about its metabolic implications. The
      aim of the present study was to evaluate the metabolic implications of glucose
      absorption, sodium removal, protein loss into the dialysate, and catabolism in
      AKI patients undergoing high-volume PD and to identify risk factors associated
      with those metabolic effects. METHODS: A prospective cohort study over 18
      consecutive months evaluated 208 sessions of high-volume PD performed in 31 AKI
      patients. One session of high-volume PD lasted 24 hours. Repeated-measures
      analysis was performed, and correlations were calculated using the Spearman test
      for continuous variables and generalized linear models for categorical variables.
      RESULTS: Glucose absorption remained at approximately 35.3% +/- 10.5% per
      session. Protein loss measured 4.2 +/- 6.1 g daily, with higher values initially,
      which declined significantly after 2 sessions. Nitrogen balance (NB) was
      initially negative, but stabilized at approximately zero after 3 sessions.
      Glucose uptake was positively correlated with the Acute Tubular Necrosis
      Individual Severity Score [ATNISS (r = 0.21, p = 0.0036)], C-reactive protein (r
      = 0.26, p = 0.0167), protein loss (r = 0.36, p < 0.0001), and sodium removal (r =
      0.24, p = 0.002). Protein loss was positively correlated with sodium removal (r =
      0.22, p = 0.0085) and gastrointestinal disease (p = 0.0004). Sodium removal was
      positively correlated with serum sodium (r = 0.21, p = 0.0064), ATNISS (r = 0.15,
      p = 0.0411), urea nitrogen appearance [UNA (r = 0.24, p = 0.0019)], and fluid
      overload as an indication for dialysis (p < 0.0001). Urea nitrogen appearance was
      positively correlated with the indication for dialysis (electrolyte disturbances:
      p = 0.0287) and negatively correlated with nephrotoxic AKI (p < 0.0001). Nitrogen
      balance was negatively correlated with UNA (r = -0.389, p < 0.0001) and ischemic
      AKI (p = 0.0047). CONCLUSIONS: High-volume PD did not increase hypercatabolism in
      AKI patients, and protein loss and glucose uptake remained constant during
      treatment. Those parameters were influenced by the clinical condition of the
      patients, including the cause of AKI, inflammation, and comorbidities-factors
      that should be known before the prescription of dialysis and nutrition, thus
      avoiding metabolic complications such as hyperglycemia, hypernatremia, and
      worsening catabolism.

PMID- 24335125
TI  - Automated peritoneal dialysis prescriptions for enhancing sodium and fluid
      removal: a predictive analysis of optimized, patient-specific dwell times for the
      day period.
AB  - BACKGROUND: Remaining edema-free is a challenge for many automated peritoneal
      dialysis (APD) patients, especially those with fast ("high") transport
      characteristics. Although increased use of peritoneal dialysis (PD) solutions
      with high glucose concentrations may improve volume control, frequent use of such
      solutions is undesirable. METHODS: We used the 3-pore kinetic model to evaluate 4
      alternative therapy prescriptions for the APD day exchange in anuric patients
      with high, high-average, and low-average transport characteristics. Four
      prescriptions were modeled: Therapy 1: Optimal, individualized dwell times with a
      dry period. Therapy 2: Use of a midday exchange. Therapy 3: Use of an icodextrin
      containing dialysate during a 14-hour dwell. Therapy 4: Use of optimal,
      individualized dwell times, followed by an icodextrin dwell to complete the
      daytime period. The alternative therapies were compared with a reference standard
      therapy using glucose solution during a 14-hour dwell. The nighttime prescription
      was identical in all cases (10 L over 10 hours), and all glucose solutions
      contained 2.27% glucose. Net ultrafiltration (UF), sodium removal (NaR), total
      carbohydrate (CHO) absorption, and weekly urea Kt/V for a 24-hour period were
      computed and compared. RESULTS: The UF and NaR were substantially higher with
      therapy 1 than with standard therapy (1034 mL vs 621 mL and 96 mmol vs 51 mmol
      respectively), without significant changes in CHO absorption or urea Kt/V.
      However, therapy 1 resulted in reduced beta2-microglobulin clearance (0.74 mL/min
      vs 0.89 mL/min with standard therapy). Compared with therapy 1, therapy 2
      improved UF and NaR (1062 mL vs 1034 mL and 99 mmol vs 96 mmol); however, that
      improvement is likely not clinically significant. Therapy 2 also resulted in a
      higher Kt/V (2.07 vs 1.72), but at the expense of higher glucose absorption
      (difference: 42 g). The UF and NaR were highest with a long icodextrin-containing
      daytime dwell either preceded by a short optimized dwell (1426 mL and 155 mmol)
      or without such a dwell (1327 mL and 148 mmol). CONCLUSIONS: The 3-pore model
      predictions revealed that patient-specific optimal dwell times and regimens with
      a longer day dwell might provide improved UF and NaR options in APD patients with
      a variety of peritoneal membrane transport characteristics. In patients without
      access to icodextrin, therapy 1 might enhance UF and NaR and provide a short-term
      option to increase fluid removal. Although that approach may offer clinicians a
      therapeutic option for the overhydrated patient who requires increased UF in the
      short term, APD prescriptions including icodextrin provide a means to augment
      sodium and fluid removal. Data from clinical trials are needed to confirm the
      predictions from this study.

PMID- 24335126
TI  - Longitudinal changes in health-related quality of life scores in Brazilian
      incident peritoneal dialysis patients (BRAZPD): socio-economic status not a
      barrier.
AB  - BACKGROUND AND OBJECTIVES: A large proportion of the patients on peritoneal
      dialysis (PD) in Brazil have low levels of education and family income. The
      present study assessed whether education level and family income are associated
      with baseline and longitudinal changes in health-related quality of life (HRQOL)
      scores during the first year of PD therapy. METHODS: We evaluated 1624 incident
      patients from the Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD) at
      baseline, and 486 of them after 12 months. The SF-36 was used to determine HRQOL
      and the Karnofsky index (KI), physical performance. RESULTS: At baseline,
      patients received high KI scores compared with scores on the SF-36. The means of
      the mental and physical components at baseline and after 12 months were 39.9 +/-
      10.5 compared with 38.7 +/- 11.7 and 41.8 +/- 9.6 compared with 40.7 +/- 9.8
      respectively, which were not statistically different. A multivariate regression
      analysis showed that age, sex, diabetes, and cardiovascular disease were
      predictors of the mental component (respectively, beta = 0.12, p < 0.001; beta =
      0.11, p < 0.001; beta = -0.08, beta = 0.007; and beta = -0.07, p = 0.007) and
      that age, sex, diabetes, cardiovascular disease, hemoglobin, glucose, and
      creatinine were predictors of the physical component (respectively, beta = -0.28,
      p < 0.001; beta = 0.06, p = 0.009; beta = -0.09, p = 0.002; beta = -0.09, p =
      0.001; beta = 0.07, p = 0.004; beta = -0.05, p = 0.040; and beta = 0.05, p =
      0.040). Education level and family income were not significantly associated with
      HRQOL (mental and physical components) in the multivariate regression.
      CONCLUSIONS: The results indicate that, as predictors, family income and
      education level have no impact on HRQOL, supporting the idea that socio-economic
      status should not be a barrier to the selection of PD as a treatment modality in
      Brazil.

PMID- 24335127
TI  - Thyrotropin and free thyroxine concentrations do not affect cardiovascular
      disease and mortality in euthyroid peritoneal dialysis patients.

PMID- 24335128
TI  - A novel technique for repositioning, under local anesthetic, malfunctioning and
      migrated peritoneal dialysis catheters.

PMID- 24335129
TI  - Black-stained peritoneal dialysis tubing: a national survey.

PMID- 24335130
TI  - Intraperitoneal compared with intravenous meropenem for peritoneal dialysis
      related peritonitis.

PMID- 24335131
TI  - Bariatric surgery in a patient on peritoneal dialysis.

PMID- 24335132
TI  - Peritoneal dialysis peritonitis caused by Bacteroides thetaiotaomicron.

PMID- 24335133
TI  - Normal peritoneum after nine years of peritoneal dialysis with biocompatible
      dialysate: a case report.

PMID- 24335134
TI  - Are patients prepared to use telemedicine in home peritoneal dialysis programs?

PMID- 24335135
TI  - Cancer antigen 125 as a biomarker in peritoneal dialysis: mesothelial cell health
      or death?

PMID- 24335136
TI  - Re: Cancer antigen 125 as a biomarker in peritoneal dialysis: mesothelial cell
      health or death?

PMID- 24335139
TI  - Fine needle aspiration of oncocytic variants of pancreatic neuroendocrine tumor:
      a report of three misdiagnosed cases.
AB  - OBJECTIVES: An oncocytic variant of pancreatic neuroendocrine tumors (PanNET) is
      exceedingly rare. Here we report cytomorphological features of the oncocytic
      variant of PanNET and discuss how to avoid diagnostic pitfalls. STUDY DESIGN: A
      computerized search of our laboratory information system was performed over an 18
      year period to identify all cytology and surgical pathology cases where a
      diagnosis of PanNET was made or considered in the differential diagnosis. Three
      cases of the oncocytic variant of PanNET were identified. RESULTS: Endoscopic
      ultrasound-guided fine needle aspiration (FNA) smears showed cohesive clusters of
      large atypical cells with abundant eosinophilic granular cytoplasm,
      anisonucleosis, nuclear enlargement and overlapping, prominent nucleoli, and a
      relatively smooth nuclear membrane. Nuclei were round to oval with finely
      granular chromatin. Additional features included rare isolated cells and
      glandular formation. Some of these morphological features, such as
      anisonucleosis, nuclear enlargement, and overlapping, prominent nucleoli, are
      also commonly seen in the pancreatic adenocarcinoma. All these cases were
      misclassified by FNA as adenocarcinoma (2 cases) or suspicious for carcinoma (1
      case) and were histologically confirmed to be oncocytic variants of PanNET.
      CONCLUSIONS: Useful salient features of the oncocytic variant of PanNET include
      abundant eosinophilic granular cytoplasm, finely granular chromatin, and
      relatively smooth nuclear membrane. The awareness of this variant will help to
      avoid misdiagnosis.

PMID- 24335140
TI  - Obesity-related adipokines predict patient-reported shoulder pain.
AB  - BACKGROUND/AIMS: Increasingly, an inflammatory modulating effect of adipokines
      within synovial joints is being recognized. To date, there has been no work
      examining a potential association between the presence of adipokines in the
      shoulder and patient-reported outcomes. This study undertakes an investigation
      assessing these potential links. METHODS: 50 osteoarthritis patients scheduled
      for shoulder surgery completed a pre-surgery questionnaire capturing demographic
      information including validated, patient-reported function (Disabilities of the
      Arm, Shoulder, and Hand questionnaire) and pain (Short Form McGill Pain
      Questionnaire) measures. Synovial fluid (SF) samples were analyzed for leptin,
      adiponectin, and resistin levels using Milliplex MAP assays. Linear regression
      modeling was used to assess the association between adipokine levels and patient
      reported outcomes, adjusted for age, sex, BMI, and disease severity. RESULTS: 54%
      of the cohort was female (n = 27). The mean age (SD) of the sample was 62.9 (9.9)
      years and the mean BMI (SD) was 28.1 (5.4) kg/m(2). From regression analyses,
      greater SF leptin and adiponectin levels, but not regarding resistin, were found
      to be associated with greater pain (p < 0.05). Adipokine levels were not
      associated with functional outcome scores. CONCLUSIONS: The identified
      association between shoulder-derived SF leptin and adiponectin and shoulder pain
      is likely explained by the pro-inflammatory characteristics of the adipokines and
      represents potentially important therapeutic targets.

PMID- 24335141
TI  - Type I and II pneumocyte differentiation in the developing fetal chicken lung:
      conservation of pivotal proteins from birds to human in the struggle for life at
      birth.
AB  - BACKGROUND: Antenatal corticosteroids and surfactant replacement therapy have
      dramatically reduced mortality caused by lung disease in premature babies.
      Knowledge about mechanisms regulating epithelial differentiation of the
      respiratory membrane is limited, as are effects of pharmacological interventions.
      The chicken fetus is a valuable model for exploring pharmacological actions on
      developing organs. However, more precise information about the timing of
      developmental events in the chicken lung is needed for human correlation.
      OBJECTIVES: Characterization of morphological development and protein expression
      in the respiratory membrane of the developing chicken lung to create a platform
      for pharmacological testing in a human context. METHODS: Fetal chicken lungs,
      embryonic days (E) 7-20, were characterized by morphology and protein expression
      of epithelial differentiation markers. This was compared with publications on the
      same processes during human lung development. RESULTS: The respiratory membranes
      of developing chicken and human lungs show basic similarities. In chicken,
      surfactant protein B is expressed in cuboidal type II epithelial cells from E17.
      Aquaporin 5 is expressed in the epithelium from E7 and selectively in type I
      pneumocytes from E17. The type I pneumocyte and endothelial marker, caveolin 1,
      is expressed in the endothelium from E7 to E20. CONCLUSION: Despite phylogenetic
      distance, central aspects of cellular development in the chicken and human lung
      are similar. The fetal chicken model has important additional advantages to
      mammalian models, including fetal independence and short incubation, and is thus
      well suited for in vivo studies of lung maturation relevant to human development.

PMID- 24335143
TI  - Dental caries and microbiota in children with black stain and non-discoloured
      dental plaque.
AB  - AIM: We aimed to assess caries experience and microbiota in systemically healthy
      children with black stain (BS) and non-discoloured plaque. METHODS: Forty-six
      children with BS and 47 counterparts with non-discoloured plaque aged 7.9 +/- 1.3
      years were clinically examined. Dental caries was scored using WHO criteria.
      Samples of BS and non-discoloured dental plaque were collected from tooth
      surfaces. The DNA of the samples was extracted and real-time PCR was performed to
      determine the total number of bacteria and the species Streptococcus mutans, S.
      sobrinus, Lactobacillus sp., Actinomyces naeslundii, Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and
      Fusobacterium nucleatum. RESULTS: Children with BS had lower DMFT (p = 0.013),
      lower DT values (p = 0.005) and a tendency to lower caries prevalence (p = 0.061)
      than children with non-discoloured plaque. Plaque samples of the BS group
      contained higher numbers of A. naeslundii (p = 0.005) and lower numbers of F.
      nucleatum (p = 0.001) and Lactobacillus sp. (p = 0.001) compared to the non
      discoloured plaque samples of the control group. Comparing the children with BS
      and non-discoloured plaque, higher counts for A. naeslundii (p = 0.013) were
      observed in caries-free children with BS while in caries-affected children with
      BS, lower counts of F. nucleatum (p = 0.007) were found. Counts of Lactobacillus
      sp. were higher in non-discoloured plaque samples than in BS of caries-free and
      caries-affected children. CONCLUSION: Results suggest that the different
      microbial composition of BS might be associated with the lower caries experience
      in affected subjects. The role of black-pigmented bacteria associated with
      periodontitis needs further studies.

PMID- 24335142
TI  - Tumor microenvironment-associated modifications of alternative splicing.
AB  - Pre-mRNA alternative splicing is modified in cancer, but the origin and
      specificity of these changes remain unclear. Here, we probed ovarian tumors to
      identify cancer-associated splicing isoforms and define the mechanism by which
      splicing is modified in cancer cells. Using high-throughput quantitative PCR, we
      monitored the expression of splice variants in laser-dissected tissues from
      ovarian tumors. Surprisingly, changes in alternative splicing were not limited to
      the tumor tissues but were also found in the tumor microenvironment. Changes in
      the tumor-associated splicing events were found to be regulated by splicing
      factors that are differentially expressed in cancer tissues. Overall, ~20% of the
      alternative splicing events affected by the down-regulation of the splicing
      factors QKI and RBFOX2 were altered in the microenvironment of ovarian tumors.
      Together, our results indicate that the tumor microenvironment undergoes specific
      changes in alternative splicing orchestrated by a limited number of splicing
      factors. 

PMID- 24335144
TI  - Human NELL1 protein augments constructive tissue remodeling with biologic
      scaffolds.
AB  - Biologic scaffolds composed of extracellular matrix (ECM) derived from
      decellularized tissues effectively reprogram key stages of the mammalian response
      to injury, altering the wound microenvironment from one that promotes scar tissue
      formation to one that stimulates constructive and functional tissue remodeling.
      In contrast, engineered scaffolds, composed of purified ECM components such as
      collagen, lack the complex ultrastructure and composition of intact ECM and may
      promote wound healing but lack factors that facilitate constructive and
      functional tissue remodeling. The objective of the present study was to test the
      hypothesis that addition of NELL1, a signaling protein that controls cell growth
      and differentiation, enhances the constructive tissue remodeling of a purified
      collagen scaffold. An abdominal wall defect model in the rat of 1.5-cm(2) partial
      thickness was used to compare the constructive remodeling of a bovine type I
      collagen scaffold to a biologic scaffold derived from small intestinal submucosa
      (SIS)-ECM with and without augmentation with 17 MUg NELL1 protein. Samples were
      evaluated histologically at 14 days and 4 months. The contractile response of the
      defect site was also evaluated at 4 months. Addition of NELL1 protein improved
      the constructive remodeling of collagen scaffolds but not SIS-ECM scaffolds.
      Results showed an increase in the contractile force of the remodeled skeletal
      muscle and a fast:slow muscle composition similar to native tissue in the
      collagen-treated group. The already robust remodeling response to SIS-ECM was not
      enhanced by NELL1 at the dose tested. These findings suggest that NELL1 protein
      does contribute to the enhanced constructive remodeling of skeletal muscle.

PMID- 24335145
TI  - Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the beta
      Catenin/TCF/LEF-1 pathway in gastric cancer cells.
AB  - Glycogen synthase kinase 3 beta (GSK3beta) is a critical protein kinase that
      phosphorylates numerous proteins in cells and thereby impacts multiple pathways
      including the beta-Catenin/TCF/LEF-1 pathway. MicroRNAs (miRs) are a class of
      noncoding small RNAs of ~22 nucleotides in length. Both GSK3beta and miR play
      myriad roles in cell functions including stem cell development, apoptosis,
      embryogenesis and tumorigenesis. Here we show that GSK3beta inhibits the
      expression of miR-96, miR-182 and miR-183 through the beta-Catenin/TCF/LEF-1
      pathway. Knockout of GSK3beta in mouse embryonic fibroblast cells increases
      expression of miR-96, miR-182 and miR-183, coinciding with increases in the
      protein level and nuclear translocation of beta-Catenin. In addition,
      overexpression of beta-Catenin enhances the expression of miR-96, miR-182 and miR
      183 in human gastric cancer AGS cells. GSK3beta protein levels are decreased in
      human gastric cancer tissue compared with surrounding normal gastric tissue,
      coinciding with increases of beta-Catenin protein, miR-96, miR-182, miR-183 and
      primary miR-183-96-182 cluster (pri-miR-183). Furthermore, suppression of miR-183
      96-182 cluster with miRCURY LNA miR inhibitors decreases the proliferation and
      migration of AGS cells. Knockdown of GSK3beta with siRNA increases the
      proliferation of AGS cells. Mechanistically, we show that beta-Catenin/TCF/LEF-1
      binds to the promoter of miR-183-96-182 cluster gene and thereby activates the
      transcription of the cluster. In summary, our findings identify a novel role for
      GSK3beta in the regulation of miR-183-96-182 biogenesis through beta
      Catenin/TCF/LEF-1 pathway in gastric cancer cells. 

PMID- 24335148
TI  - Susac syndrome treated with subcutaneous immunoglobulin.
AB  - BACKGROUND: Susac syndrome is a rare disease characterized by the triad of
      encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss
      mainly affecting young women. The finding of antibodies against the endothelium
      in the sera of these patients has supported the hypothesis of an autoimmune
      endotheliopathy of the brain, inner ear and retina. Because of the rarity of the
      disease, treatment is based on the knowledge of case reports and small case
      series. Medical therapy consists of glucocorticoids, immunosuppressants, acetyl
      salicylic acid, and immunomodulatory agents such as intravenous immunoglobulin.
      METHODS: We present the case histories of 2 young women with Susac syndrome
      presenting with several episodes of encephalopathy, branch retinal artery
      occlusions, and hearing loss that were treated with different immunosuppressive
      drugs, glucocorticoids and intravenous immunoglobulin. In the course of the
      disease, the treatment was successfully switched to subcutaneous immunoglobulin
      without any further relapse in both patients. CONCLUSION: We conclude that the
      application of subcutaneous immunoglobulin is easy to learn, helps to reduce in
      hospital costs and enables a more flexible everyday life. The treatment with
      subcutaneous immunoglobulin helps to reduce immunosuppressants and appears to
      prevent relapses.

PMID- 24335147
TI  - TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase
      I and PARP mechanisms with potential applications for cancer therapy.
AB  - Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of
      endogenous DNA breakage, contributing to hereditary ataxia and underlying the
      cytotoxicity of a wide range of anti-cancer agents. Despite their frequency, the
      overlapping mechanisms that repair these forms of DNA breakage are largely
      unknown. Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1)
      sensitizes human cells to alkylation damage and the additional depletion of
      apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that
      observed for TDP1 or APE1 depletion alone. Quantification of DNA breaks and
      clonogenic survival assays confirm a role for TDP1 in response to base damage,
      independently of APE1. The hypersensitivity to alkylation damage is partly
      restored by depletion of Top1, illustrating that alkylating agents can trigger
      cytotoxic Top1-breaks. Although inhibition of PARP activity does not sensitize
      TDP1-deficient cells to Top1 poisons, it confers increased sensitivity to
      alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in
      response to genotoxic challenge. Finally, we demonstrate that cancer cells in
      which TDP1 is inherently deficient are hypersensitive to alkylation damage and
      that TDP1 depletion sensitizes glioblastoma-resistant cancer cells to the
      alkylating agent temozolomide. 

PMID- 24335149
TI  - Genetic analysis of GHR should contain sequencing of all coding exons and
      specific intron sequences, and screening for exon deletions.
AB  - BACKGROUND: The work-up of patients with clinical and/or biochemical features of
      growth hormone insensitivity (GHI) usually contains genetic analysis of the
      growth hormone receptor (GHR) gene, and if negative, of STAT5B, IGFALS and IGF1.
      In a previous report we described 2 siblings presenting with short stature, low
      IGF-1 levels, elevated GH secretion and no increase of IGF-1 after 1 week of GH
      administration. Repeated analysis of the GHR showed no abnormalities; however,
      further testing revealed a heterozygous STAT5B defect in both siblings. SUBJECTS
      AND METHODS: Two boys of Surinam-Hindustan origin showed growth failure up to the
      age of 6-7 years, followed by partial catch-up growth associated with increasing
      body mass index. Reanalysis of GHR including published intronic sequences was
      performed on the patients' DNA collected 7 years earlier. RESULTS: The
      heterozygous STAT5B variant proved to be functionally benign. A homozygous
      intronic mutation of the GHR, c.618+792A>G (IVS6+792A>G), was subsequently found,
      resulting in the activation of pseudoexon 6psi, and explaining the GHI phenotype
      of the patients. CONCLUSION: An intronic GHR mutation should be considered in all
      patients with signs of GHI and no coding exon mutations, even if the phenotype is
      mild and even if other genetic variants have been found.

PMID- 24335146
TI  - Systematic discovery and characterization of regulatory motifs in ENCODE TF
      binding experiments.
AB  - Recent advances in technology have led to a dramatic increase in the number of
      available transcription factor ChIP-seq and ChIP-chip data sets. Understanding
      the motif content of these data sets is an important step in understanding the
      underlying mechanisms of regulation. Here we provide a systematic motif analysis
      for 427 human ChIP-seq data sets using motifs curated from the literature and
      also discovered de novo using five established motif discovery tools. We use a
      systematic pipeline for calculating motif enrichment in each data set, providing
      a principled way for choosing between motif variants found in the literature and
      for flagging potentially problematic data sets. Our analysis confirms the known
      specificity of 41 of the 56 analyzed factor groups and reveals motifs of
      potential cofactors. We also use cell type-specific binding to find factors
      active in specific conditions. The resource we provide is accessible both for
      browsing a small number of factors and for performing large-scale systematic
      analyses. We provide motif matrices, instances and enrichments in each of the
      ENCODE data sets. The motifs discovered here have been used in parallel studies
      to validate the specificity of antibodies, understand cooperativity between data
      sets and measure the variation of motif binding across individuals and species. 

PMID- 24335150
TI  - Disturbed vesicular trafficking of membrane proteins in prion disease.
AB  - The pathogenic mechanism of prion diseases remains unknown. We recently reported
      that prion infection disturbs post-Golgi trafficking of certain types of membrane
      proteins to the cell surface, resulting in reduced surface expression of membrane
      proteins and abrogating the signal from the proteins. The surface expression of
      the membrane proteins was reduced in the brains of mice inoculated with prions,
      well before abnormal symptoms became evident. Prions or pathogenic prion proteins
      were mainly detected in endosomal compartments, being particularly abundant in
      recycling endosomes. Some newly synthesized membrane proteins are delivered to
      the surface from the Golgi apparatus through recycling endosomes, and some
      endocytosed membrane proteins are delivered back to the surface through recycling
      endosomes. These results suggest that prions might cause neuronal dysfunctions
      and cell loss by disturbing post-Golgi trafficking of membrane proteins via
      accumulation in recycling endosomes. Interestingly, it was recently shown that
      delivery of a calcium channel protein to the cell surface was impaired and its
      function was abrogated in a mouse model of hereditary prion disease. Taken
      together, these results suggest that impaired delivery of membrane proteins to
      the cell surface is a common pathogenic event in acquired and hereditary prion
      diseases. 

PMID- 24335151
TI  - Lipopolysaccharide-binding protein as marker of fetal inflammatory response
      syndrome after preterm premature rupture of membranes.
AB  - BACKGROUND: Intra-amniotic inflammation with preterm premature rupture of
      membranes (PPROM) is a risk factor for fetal inflammatory response syndrome
      (FIRS) and adverse neonatal outcome. OBJECTIVES: To evaluate the diagnostic
      accuracy of lipopolysaccharide-binding protein (LBP) for detecting FIRS in
      preterm neonates born after PPROM. METHODS: This was a prospective study in the
      level III neonatal intensive care unit (42 neonates; 23 + 6 to 31 + 6 weeks'
      gestation) of mothers with PPROM. Umbilical cord blood concentrations of LBP, C
      reactive protein (CRP), interleukin (IL)-6 and white blood cell count with
      differential were measured at delivery and 24 h after birth. Neonates were
      classified into FIRS (n = 22) and no FIRS (n = 20) groups according to clinical
      criteria and IL-6 level (>=17.5 pg/ml). Histological examination of the placenta
      and umbilical cord was performed. Neurological examination at 12 months'
      corrected age was performed. RESULTS: Umbilical cord blood concentration of LBP
      was significantly higher in the FIRS group than in the no FIRS group at delivery
      (median 21.6 mg/l vs. median 2.3 mg/l; p < 0.0001) and 24 h after birth (median
      17.2 mg/l vs. median 20.0 mg/l; p < 0.001). The area under the ROC curve for FIRS
      at delivery was 0.98 (95% CI 0.88-1.0) for LBP, 0.92 (95% CI 0.80-0.99) for CRP
      and 0.82 (95% CI 0.64-0.94) for immature to total neutrophil ratio. Similar
      results were obtained if FIRS was defined by funisitis. Umbilical cord blood
      concentration of LBP at delivery was significantly higher in neonates with
      abnormal neurological exam at 12 months than in those with normal exam (median
      19.5 mg/l vs. median 3.75 mg/l; p < 0.015). CONCLUSIONS: In preterm neonates born
      to asymptomatic women with PPROM, LBP in cord blood at delivery is an excellent
      diagnostic biomarker of FIRS/funisitis with prognostic potential.

PMID- 24335153
TI  - The effect of insoles on foot pain and daily activities.
AB  - BACKGROUND: Foot pain decreases individuals' ability to perform daily activities.
      Insoles are often prescribed to reduce the pain which, in turn, may promote
      return to normal activities. OBJECTIVES: To evaluate the effects of insoles on
      foot pain and daily activities, and to investigate the relationship between
      individuals' satisfaction with insoles and actual use of them. STUDY DESIGN: A 4
      week pre-post intervention follow-up. METHODS: Brief Pain Inventory,
      International Physical Activity Questionnaire and Lower Extremities Functional
      Status were used as outcome measures. Client Satisfaction with Device was used in
      the follow-up. RESULTS: A total of 67 participants answered the questionnaires
      (81% women). Overall, a reduction in Pain Severity (p = 0.002) and Pain
      Interference (p = 0.008) was shown. Secondary analyses revealed a significant
      effect only in women. No changes in daily activities (Walking, p = 0.867; Total
      Physical Activity, p = 0.842; Lower Extremities Functional Status, p = 0.939)
      could be seen. There was no relation between Client Satisfaction with Device
      measures and duration of insole use. A difference in sex was shown; women scored
      higher than men on Pain Severity. CONCLUSION: Insoles reduce pain and pain
      interference with daily activities for women with foot pain. Satisfaction with
      the insoles is not a predictor of actual insole use. The effect of insoles on
      activity performance needs further study. CLINICAL RELEVANCE: This study provides
      evidence for prescribing insoles to people with foot pain. Nonetheless, insoles
      are not enough to increase their physical activity level in the short term.
      Satisfaction with insoles and duration of use are not correlated and cannot be
      inferred from each other.

PMID- 24335152
TI  - Acceptable but limited efficacy of capecitabine-based doublets in the first-line
      treatment of metastatic triple-negative breast cancer: a pilot study.
AB  - BACKGROUND: This open-label, nonrandomized phase II clinical trial investigated
      the efficacy of capecitabine-based doublets in the first-line treatment of
      metastatic triple-negative breast cancer (mTNBC). METHODS: Eligible mTNBC women
      with measurable diseases were recruited to receive either TX regimen (docetaxel
      75 mg/m(2) i.v. on day 1 plus capecitabine 1,000 mg/m(2) b.i.d. on days 1-14
      every 3 weeks) or NX regimen (vinorelbine 25 mg/m(2) i.v. on days 1 and 8 plus
      capecitabine 1,000 mg/m(2) b.i.d. on days 1-14 every 3 weeks) for up to 6 cycles
      until disease progression or unacceptable toxicity. The primary end point was
      objective response rate (ORR) and secondary end points included progression-free
      survival (PFS), overall survival (OS) and clinical benefit rate (CBR). RESULTS:
      Forty-five mTNBC patients, 27 in TX and 18 in NX were recruited. The total ORR
      was 20.0% and CBR was 40%. After a median follow-up of 28 months, PFS was 5.2
      months (95% CI, 4.1-6.3 months) and OS was 18.2 months (95% CI, 8.7-27.7 months).
      The response rate was numerically but not statistically lower in the TX group
      than in the NX group (27.8 vs. 14.8%, p = 0.449). No difference was found in
      either PFS (4.9 vs. 5.2 months, p = 0.483) or OS (21.5 vs. 18.3 months, p =
      0.964) between the two regimens. CONCLUSIONS: Although the OS seems to be
      reasonable, the efficacy of capecitabine-containing TX or NX regimen was limited
      in terms of response and PFS in mTNBC patients, suggesting capecitabine-based
      doublet may be acceptable but has limited potency in this subtype.

PMID- 24335155
TI  - Assessment of fetal sex chromosome aneuploidy using directed cell-free DNA
      analysis.
AB  - OBJECTIVE: To examine the performance of chromosome-selective sequencing of cell
      free (cf) DNA in maternal blood for assessment of fetal sex chromosome
      aneuploidies. METHODS: This was a case-control study of 177 stored maternal
      plasma samples, obtained before fetal karyotyping at 11-13 weeks of gestation,
      from 59 singleton pregnancies with fetal sex chromosome aneuploidies (45,X, n =
      49; 47,XXX, n = 6; 47,XXY, n = 1; 47,XYY, n = 3) and 118 with euploid fetuses
      (46,XY, n = 59; 46,XX, n = 59). Digital analysis of selected regions (DANSRTM) on
      chromosomes 21, 18, 13, X and Y was performed and the fetal-fraction optimized
      risk of trisomy evaluation (FORTETM) algorithm was used to estimate the risk for
      non-disomic genotypes. Performance was calculated at a risk cut-off of 1:100.
      RESULTS: Analysis of cfDNA provided risk scores for 172 (97.2%) samples; 4
      samples (45,X, n = 2; 46,XY, n = 1; 46,XX, n = 1) had an insufficient fetal cfDNA
      fraction for reliable testing and 1 case (47,XXX) failed laboratory quality
      control metrics. The classification was correct in 43 (91.5%) of 47 cases of
      45,X, all 5 of 47,XXX, 1 of 47,XXY and 3 of 47,XYY. There were no false-positive
      results for monosomy X. DISCUSSION: Analysis of cfDNA by chromosome-selective
      sequencing can correctly classify fetal sex chromosome aneuploidy with reasonably
      high sensitivity.

PMID- 24335154
TI  - Priorities in lower limb prosthetic service delivery based on an international
      survey of prosthetists in low- and high-income countries.
AB  - BACKGROUND: Prosthetic services, including the provision of an appropriate
      prosthesis, are a crucial part of the rehabilitation process for individuals with
      lower limb amputations. However, globally there exist unique challenges in the
      delivery of prosthetic services that are limiting rehabilitation outcomes and
      consequently the well-being and socio-economic status of individuals with lower
      limb amputations. OBJECTIVES: The objective of this work was to explore the
      issues related to the provision of appropriate prosthetic technologies and to
      compare these across different economies of the world. STUDY DESIGN: Cross
      sectional survey. METHODS: An online survey was developed and distributed to
      prosthetic practitioners providing services in countries around the world. An
      open-coding thematic content analysis procedure was applied to extract key themes
      from the data. RESULTS: The response codes defined three overall themes of lower
      limb prosthetic delivery, and several key differences between higher and lower
      income countries emerged. Namely, a higher emphasis on part/material
      availability, practitioner training and durability in lower income countries was
      found. High costs were an issue raised by practitioners in all countries.
      CONCLUSION: Practitioners around the world share many of the same concerns;
      however, some lower income countries face important and pressing issues that
      limit their ability to provide adequate prosthetic services. CLINICAL RELEVANCE:
      This work highlights the most crucial service and technology-related needs, as
      perceived by trained prosthetic practitioners, of populations requiring lower
      limb prosthetic treatment around the world. Additionally, the results may be used
      to prioritize prosthetic-related health-care initiatives led by other
      researchers, governments and organizations working to improve services
      internationally.

PMID- 24335156
TI  - Timely diagnosis of malalignment of the distal extremities is crucial in morbidly
      obese juveniles.
AB  - BACKGROUND/AIMS: To determine i) whether obesity in childhood can be related to
      malalignment of the distal extremities, ii) the proportion of genu valgum
      malalignment and abduction setting, and iii) the respective deviation dominance
      in children who are morbidly obese. METHODS: 31 morbidly obese Caucasian children
      (16 males) recruited for the STYJOBS Study (ClinicalTrials.gov Identifier
      NCT00482924) with a mean age of 13.9 +/- 0.5 years, a mean height of 162.3 +/-
      2.7 cm, a mean weight of 90.62 +/- 5.0 kg, and a mean BMI of 33.8 +/- 1.2 kg/m(2)
      were clinically examined using the Mikulicz line in order to assess load
      distribution on the knee joint. 21 participants received a whole-leg X-ray
      because of a clinically estimated malalignment. RESULTS: 8/31 participants
      examined were diagnosed with genu valgum, 1/31 with genu varum, and 22/31 did not
      have any malalignment of the femur or tibia. The majority of genu valgum
      presentation was due to femoral deviation. Of those without malalignment, 4/22
      participants had an abduction setting, while 2/22 showed an adduction of the leg.
      CONCLUSION: Genu valgum as a predominant malalignment of the distal extremities
      is frequent in youth with morbid obesity. Timely guided correction of angular
      deformity of the knee seems pivotal in order to avoid osteotomy or osteoarthritis
      later in life.

PMID- 24335157
TI  - Reproducibility and diagnostic outcomes of two visual-tactile criteria used by
      dentists to assess caries lesion activity: a cross-over study.
AB  - The aim of this study was to evaluate the reproducibility and differences in
      diagnostic outcomes by practicing dental clinicians previously inexperienced in
      using the Nyvad criteria and the ICDAS II criteria with the Lesion Activity
      Assessment system (ICDAS II + LAA). Four volunteer dentists were randomly
      allocated to one of two groups. Both groups of dentists examined the same
      voluntary sample (n = 140) of caries active young adults using Nyvad and ICDAS II
      + LAA criteria in different sequences. The first group used the Nyvad criteria
      during period 1, followed by ICDAS II + LAA during period 2; the second group did
      the examinations in the opposite sequence. Before the period 1 and 2
      examinations, dentists from both groups were trained with the Nyvad or ICDAS II +
      LAA criteria, depending on the group to which they were assigned. Intra-examiner
      agreement for lesion severity was high for both diagnostic instruments (weighted
      kappa 0.62-0.80). For lesion activity the intra-examiner unweighted kappa values
      ranged from 0.31 to 0.61 for ICDAS II + LAA and from 0.36 to 0.51 for Nyvad. The
      mean number of active non-cavitated caries lesions was significantly higher for
      ICDAS II + LAA (6.14 +/- 5.4) than for Nyvad (3.90 +/- 3.9) (p < 0.001). Active
      cavitated/dentinal caries lesions were significantly higher for ICDAS II + LAA
      (4.14 +/- 4.1) than for Nyvad (2.13 +/- 3.1) (p < 0.001). Both the Nyvad and
      ICDAS II + LAA diagnostic criteria showed high reproducibility for lesion
      severity assessment. The mean number of active caries lesions among high caries
      risk subjects was significantly higher using the ICDAS II + LAA criteria, which
      may subsequently lead to more caries treatment. TRIAL REGISTRATION:
      ISRCTN65592532.

PMID- 24335158
TI  - Expenses for meetings and fees for service: details of 'disclosure' required of
      pharmaceutical companies.

PMID- 24335159
TI  - Prognostic role of maternal neutrophil gelatinase-associated lipocalin in women
      with severe early-onset preeclampsia.
AB  - INTRODUCTION: The association between maternal plasma levels of neutrophil
      gelatinase-associated lipocalin (NGAL) and maternal complications in women
      admitted with severe early-onset preeclampsia was evaluated. MATERIAL AND
      METHODS: Plasma levels of NGAL were measured at admission in patients with severe
      early-onset (presenting before 34 weeks) preeclampsia. The maternal outcome of
      women with elevated plasma levels was compared with those with normal levels.
      Maternal complications included eclampsia, HELLP syndrome, acute renal failure,
      subcapsular hepatic hematoma, pulmonary edema and disseminated intravascular
      disease. RESULTS: Sixty-seven patients were included. The median NGAL plasma
      levels in the group of women who subsequently had a complication were
      significantly higher than in those uncomplicated cases (114.8 vs. 84.2 ng/ml;
      Mann-Whitney U test p = 0.03). Maternal complications were more common in the
      elevated (>100 ng/ml) NGAL group (58.3 vs. 25.6%; chi(2) test p = 0.008), with an
      OR of 4.1 (95% CI 1.4-11.8). After adjustment by gestational age at onset, the
      association between elevated NGAL plasma levels and maternal complications
      remained significant (OR 4.2; 95% CI 1.4-12.4). DISCUSSION: Women with severe
      early-onset preeclampsia are at higher risk of maternal complications if plasma
      levels of NGAL are elevated.

PMID- 24335160
TI  - Taking advantage of physiological proteolytic processing of the prion protein for
      a therapeutic perspective in prion and Alzheimer diseases.
AB  - Prion and Alzheimer diseases are fatal neurodegenerative diseases caused by
      misfolding and aggregation of the cellular prion protein (PrP(C)) and the beta
      amyloid peptide, respectively. Soluble oligomeric species rather than large
      aggregates are now believed to be neurotoxic. PrP(C) undergoes three proteolytic
      cleavages as part of its natural life cycle, alpha-cleavage, beta-cleavage, and
      ectodomain shedding. Recent evidences demonstrate that the resulting secreted
      PrP(C) molecules might represent natural inhibitors against soluble toxic
      species. In this mini-review, we summarize recent observations suggesting the
      potential benefit of using PrP(C)-derived molecules as therapeutic agents in
      prion and Alzheimer diseases.

PMID- 24335161
TI  - School Oral Health Program in Kuwait.
AB  - The School Oral Health Program (SOHP), Kuwait, is a joint venture between the
      Ministry of Health, Kuwait, and Forsyth Institute, Cambridge, Mass., USA. This
      program provides oral health education, prevention and treatment to almost
      280,000 public school children in Kuwait. Services are delivered through a system
      of center- and school-based clinics and preventive mobile teams. One of the
      recent developments is the effective use of portable dental units for the
      delivery of preventive care to children in schools without the need for children
      to go to dental clinics. Preventive procedures performed under this program are
      the biannual application of fluoride varnish and the placement of pit and fissure
      sealants on newly erupted permanent molars and premolars. During recent years,
      the SOHP has improved its coverage of children, with prevention up to 80%. This
      has resulted in a considerable reduction in treatment needs, which is evident
      from the reduced number of composite restorations performed under this program
      during the last 6 years. This indicates that the disease level is on a decline,
      which can be confirmed from the results of the ongoing National Oral Health
      Survey on Kuwaiti school children.

PMID- 24335162
TI  - Immunological memory in innate immunity.

PMID- 24335163
TI  - Reexamining the added value of intermittent photic stimulation and
      hyperventilation in routine EEG practice.
AB  - OBJECTIVE: Investigate the added value of hyperventilation (HV) and intermittent
      photic stimulation (IPS) to the routine electroencephalogram (EEG). METHOD: This
      is a retrospective review of 1,172 successive EEGs. The records with evidence of
      epileptogenic activity were identified and further analyzed to identify if the
      activation techniques could trigger the expression of epileptic activity not seen
      otherwise in the nonactivated tracing. RESULTS: Activation procedures provided
      additional information in 9.5% of the abnormal EEG files. They helped establish
      the diagnosis of an epileptic disorder or further characterize the epileptic
      syndrome. This occurred exclusively in the younger age group (age <36 years), and
      predominantly in women. CONCLUSION: IPS and HV are easy to perform and remain
      important adjuncts to routine EEG. They may trigger the expression of
      epileptogenic activity in an otherwise uneventful EEG. Whereas their diagnostic
      value was obvious in the younger age group, we found no evidence to support their
      usefulness in the middle-age and elderly groups.

PMID- 24335164
TI  - Effect of gallium on growth of Streptococcus mutans NCTC 10449 and dental
      tissues.
AB  - Gallium-doped phosphate-based glasses (Ga-PBG) were assessed for their impact on
      Streptococcus mutans and dental mineralisation, firstly by disc diffusion assays
      followed by biofilms grown on nitrocellulose filter membrane (NFM) and constant
      depth film fermentor (CDFF). Short-time exposure (10 min) effects of Ga-PBG on S.
      mutans biofilm were compared with that of 0.2% chlorhexidine. The effects of Ga
      PBG on bovine enamel (which was investigated under pH-cycling condition) and
      dentine were analysed using transverse microradiography (TMR), profilometry and
      inductively coupled plasma optical-emission spectrometry (ICP-OES). The disc
      diffusion assays showed inhibition zones of 24.5 +/- 0.5 mm for Ga-PBG compared
      with controls (C-PBG). Ga-PBG showed statistically significant growth inhibition
      of S. mutans biofilms on NFM (p = 0.001) and CDFF (p < 0.046) compared with
      hydroxyapatite (HA) and C-PBG. The CDFF assay revealed a maximum of 2.11 log
      colony-forming unit (CFU) reduction at 48 h, but short-time exposure effects were
      comparable with that of 0.2% chlorhexidine only on older biofilms (maximum of
      0.59 vs. 0.69 log CFU reduction at 120 h). TMR analyses of the enamel revealed
      non-significant mineral loss (p = 0.37) only in the case of Ga-PBG samples
      compared with controls including sodium fluoride. ICP-OES analyses indicated
      transient gallium adsorption into dentine by calcium displacement. The results
      confirmed that gallium inhibited S. mutans growth and appears to have the
      potential to protect the enamel surface under conditions representative of the
      oral environment. Further work is needed to establish whether it has an
      application in daily oral hygiene procedures to prevent or reduce caries.

PMID- 24335165
TI  - Noninvasive fetal RhD status determination in early pregnancy.
AB  - INTRODUCTION: The aim of this study was to examine if noninvasive fetal RhD
      genotyping from maternal blood cell-free fetal DNA performed in the first
      trimester of pregnancy is accurate enough to propose its routine application to
      replace usual immunoprophylaxis. MATERIAL AND METHODS: We carried out a
      prospective study analyzing fetal RhD genotype in 149 nonimmunized RhD-negative
      women with single pregnancies between 8 and 13 weeks of gestation. Fetal RhD
      genotype was detected by quantitative PCR targeting exons 5 and 7. The results
      were compared with postnatal cord blood phenotype, and discrepancy rates were
      calculated. RESULTS: The concordance of fetal RhD genotypes in maternal plasma
      and newborn D phenotypes at delivery was 98.2%, including 1 false-positive and 1
      false-negative result. The specificity and sensitivity of the assay were 97.5%
      (95% CI 87.1-99.9) and 98.6% (95% CI 92.7-99.9), respectively, and 6.5% of the
      results were inconclusive. The application of this test in early pregnancy would
      avoid unnecessary antenatal prophylaxis in about 27% (40/143) of nonsensitized
      RhD-negative women. DISCUSSION: Determination of the fetal RhD status from cell
      free fetal DNA in maternal plasma in the first trimester of pregnancy is feasible
      and highly accurate, thus allowing consideration of replacing general routine
      immunoprophylaxis in the cases of mothers with Rh-negative fetuses.

PMID- 24335166
TI  - Hypoxia-inducible factor-1alpha dependent pathways mediate the renoprotective
      role of acetazolamide against renal ischemia-reperfusion injury.
AB  - BACKGROUND/AIMS: Acute kidney injury (AKI) is a major complication of kidney
      transplantation, resulting in early graft dysfunction. Since diuretic
      acetazolamide (AZA) has been shown to improve contrast induced AKI, we
      hypothesized that AZA also protected against ischemia-reperfusion (I/R) caused
      AKI. METHODS: An in vivo mouse renal I/R injury model and an in vitro H2O2
      stimulated HK-2 cell injury model were utilized to examine the renoprotective
      effect of AZA. Renal injury and blood flow were measured. Nitric oxide synthase
      (eNOS)/Nitric oxide (NO), cell apoptosis and hypoxia-inducible factor-1alpha (HIF
      1alpha) changes were analyzed. RESULTS: AZA reduced kidney injury scores and
      improved renal function by decreasing serum creatinine and BUN levels after I/R.
      Impaired renal blood flow was restored by increasing eNOS activities and NO
      production, as indicated by Laser Doppler imaging. TUNEL staining presented that
      AZA reduced apoptotic cells due to attenuated caspase activation and increased
      Bcl-2/Bax ratio. Furthermore, HIF-1alpha induction by AZA was demonstrated. AZA
      also enhanced in vitro NO production, reduced cell apoptosis and increased HIF
      1alpha expression. Knockdown of HIF-1alpha by RNAi confirmed that AZA exerted its
      protective role depending on HIF-1alpha. AZA's effects were significantly reduced
      by Akt inhibitor LY294002. CONCLUSIONS: The present study demonstrated that AZA
      exerted a renoprotective role against I/R induced AKI through activating HIF
      1alpha and downstream pathways.

PMID- 24335167
TI  - Dietary curcumin ameliorates aging-related cerebrovascular dysfunction through
      the AMPK/uncoupling protein 2 pathway.
AB  - BACKGROUND/AIMS: Age-related cerebrovascular dysfunction contributes to stroke,
      cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases.
      One pathogenic mechanism underlying this effect is increased oxidative stress. Up
      regulation of mitochondrial uncoupling protein 2 (UCP2) plays a crucial role in
      regulating reactive oxygen species (ROS) production. Dietary patterns are widely
      recognized as contributors to cardiovascular and cerebrovascular disease. In this
      study, we tested the hypothesis that dietary curcumin, which has an antioxidant
      effect, can improve aging-related cerebrovascular dysfunction via UCP2 up
      regulation. METHODS: The 24-month-old male rodents used in this study, including
      male Sprague Dawley (SD) rats and UCP2 knockout (UCP2-/-) and matched wild type
      mice, were given dietary curcumin (0.2%). The young control rodents were 6-month
      old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The
      AMPK/UCP2 pathway and p-eNOS in cerebrovascular and endothelial cells were
      observed by immunoblotting. RESULTS: Dietary curcumin administration for one
      month remarkably restored the impaired cerebrovascular endothelium-dependent
      vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and
      cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up
      regulated UCP2 and reduced ROS production. These effects of curcumin were
      abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin
      significantly reduced ROS production and improved cerebrovascular endothelium
      dependent relaxation in aging wild type mice but not in aging UCP2-/- mice.
      CONCLUSIONS: Curcumin improves aging-related cerebrovascular dysfunction via the
      AMPK/UCP2 pathway.

PMID- 24335168
TI  - Metformin inhibits esophagus cancer proliferation through upregulation of USP7.
AB  - BACKGROUND: Recent population studies suggest that the use of metformin is
      associated with reduced incidence and improved prognosis of certain cancers.
      METHODS: In the current study, we assessed the effect of metformin on esophagus
      cancer cells using two cell lines (Eca-109 and TE-1 cells). RESULTS: We found
      that metformin inhibited growth and decreased expression of cell-cycle regulators
      in these cells. Treatment with metformin was also associated with activation of
      AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells. However,
      inhibition of AMPK signaling has little impact on the anti-proliferative roles of
      metformin. In addition, we found USP7, a positive regulator of tumor suppressor
      p53, as a new molecular target of metformin. Esophagus cancer cells can be
      protected against metformin-induced growth inhibition by small interfering RNA
      against USP7. CONCLUSION: These results provide evidence for a mechanism that may
      contribute to the antineoplastic effects of metformin suggested by recent
      population studies and justify further work to explore potential roles for it in
      esophagus cancer prevention and treatment.

PMID- 24335170
TI  - Visfatin reduces gap junction mediated cell-to-cell communication in proximal
      tubule-derived epithelial cells.
AB  - BACKGROUND/AIMS: In the current study we examined if the adipocytokine, visfatin,
      alters connexin-mediated intercellular communication in proximal tubule-derived
      epithelial cells. METHODS: The effects of visfatin (10-200ng/mL) on cell
      viability and cytotoxicity in HK2-cells were assessed by MTT, crystal violet and
      lactate dehydrogenase assays. Western blot analysis was used to confirm
      expression of Cx26, Cx40 and Cx43. The effect of visfatin (10-200ng/mL) on TGF
      beta1 secretion was confirmed by ELISA, and the effects of both TGF-beta1 (2
      10ng/mL) and visfatin (10-200ng/mL) on connexin expression were assessed by
      western blot. Functional intercellular communication was determined using
      transfer of Lucifer Yellow and paired-whole cell patch clamp electrophysiology.
      RESULTS: In low glucose (5mM), visfatin (10-200ng/mL) did not affect membrane
      integrity, cytotoxicity or cell viability at 48hrs, but did evoke a concentration
      dependent reduction in Cx26 and Cx43 expression. The expression of Cx40 was
      unaffected. At 48hrs, visfatin (10-200ng/mL) increased the secretion of TGF-beta1
      and the visfatin-evoked changes in connexin expression were mimicked by exogenous
      application of the pro-fibrotic cytokine (2-10ng/ml). Visfatin reduced dye
      transfer between coupled cells and decreased functional conductance, with levels
      falling by 63% as compared to control. Although input resistance was increased
      following visfatin treatment by 166%, the change was not significant as compared
      to control. The effects of visfatin on Cx-expression and cell-coupling were
      blocked in the presence of a TGF-beta1 specific neutralizing antibody.
      CONCLUSIONS: The adipocytokine visfatin selectively evoked a non-toxic reduction
      in connexin expression in HK2-cells. The loss in gap-junction associated proteins
      was mirrored by a loss in functional conductance between coupled cells. Visfatin
      increased TGF-beta secretion and the pattern of change for connexins expression
      was mimicked by exogenous application of TGF-beta1. The effect of visfatin on Cx
      expression and dye transfer were negated in the presence of a TGF-beta1
      neutralising antibody. These data suggest that visfatin reduces connexin-mediated
      intercellular communication in proximal tubule-derived epithelial cells via a TGF
      beta dependent pathway.

PMID- 24335169
TI  - Destabilization of heterologous proteins mediated by the GSK3beta phosphorylation
      domain of the beta-catenin protein.
AB  - BACKGROUND AND AIMS: Wnt/beta-catenin signaling plays important roles in
      development and cellular processes. The hallmark of canonical Wnt signaling
      activation is the stabilization of beta-catenin protein in cytoplasm and/or
      nucleus. The stability of beta-catenin is the key to its biological functions and
      is controlled by the phosphorylation of its amino-terminal degradation domain.
      Aberrant activation of beta-catenin signaling has been implicated in the
      development of human cancers. It has been recently suggested that GSK3betamay
      play an essential role in regulating global protein turnover. Here, we
      investigate if the GSK3beta phosphorylation site-containing degradation domain of
      beta-catenin is sufficient to destabilize heterologous proteins. METHODS AND
      RESULTS: We engineer chimeric proteins by fusing beta-catenin degradation domain
      at the N- and/or C-termini of the enhanced green fluorescent protein (eGFP). In
      both transient and stable expression experiments, the chimeric GFP proteins
      exhibit a significantly decreased stability, which can be effectively antagonized
      by lithium and Wnt1. An activating mutation in the destruction domain
      significantly stabilizes the fusion protein. Furthermore, GSK3 inhibitor SB
      216763 effectively increases the GFP signal of the fusion protein. Conversely,
      the inhibition of Wnt signaling with tankyrase inhibitor XAV939 results in a
      decrease in GFP signal of the fusion proteins, while these small molecules have
      no significant effects on the mutant destruction domain-GFP fusion protein.
      CONCLUSION: Our findings strongly suggest that the beta-catenin degradation
      domain may be sufficient to destabilize heterologous proteins in Wnt signaling
      dependent manner. It is conceivable that the chimeric GFP proteins may be used as
      a functional reporter to measure the dynamic status of beta-catenin signaling,
      and to identify potential anticancer drugs that target beta-catenin signaling.

PMID- 24335171
TI  - Berberine induces apoptosis in p53-null leukemia cells by down-regulating XIAP at
      the post-transcriptional level.
AB  - BACKGROUND: Berberine exerts anticancer activities both in vitro and in vivo
      through different mechanisms. However, the underlying molecular mechanisms of
      berberine induced p53-independent apoptosis remain unclear. METHODS: The p53-null
      leukemia cell line EU-4 cells were exposed to berberine. Then the cell viability
      and apoptosis were determined. Western blot and PCR were employed to detect the
      expression of apoptosis related protein, XIAP and MDM2. Small interfering RNA
      (siRNA) was applied to knock down endogenous expression of MDM2 and XIAP.
      RESULTS: Berberine induced p53-independent, XIAP-mediated apoptotic cell death in
      p53-null leukemia cells. Treatment with berberine resulted in suppression of XIAP
      protein in a dose- and time- dependent manner. Berberine induced down-regulation
      of XIAP protein involving inhibition of MDM2 expression and a proteasome
      dependent pathway. Moreover, inhibition of XIAP by berberine or siRNA increased
      the sensitivity of leukemia cells to doxorubicin-induced apoptosis. CONCLUSION:
      Our findings characterize the molecular mechanisms of berberine-induced caspase
      activation and subsequent apoptosis, and berberine may be a novel candidate
      inducer of apoptosis in leukemia cells, which normally lack p53 expression.

PMID- 24335172
TI  - The function role of miR-181a in chemosensitivity to adriamycin by targeting Bcl
      2 in low-invasive breast cancer cells.
AB  - OBJECTIVES: miR-181a is involved in immunity, metabolism, tumor suppression or
      carcinogenesis reported by many other studies. However, its role in the
      development of chemosensitivity to adriamycin in low-invasive breast cancer cells
      remains unclear. The aim of this study is to define the function role of miR-181a
      in promoting the efficacy of adriamycin-based neoadjuvant chemotherapy. METHODS:
      Cell survival analysis was detected by Cell Counting Kit-8 assay. Apoptotic cells
      were quantitatively detected using FITC Annexin V apoptosis Detection Kit I. Bcl
      2 protein expression was measured by western blot. Luciferase reporter vector
      with the putative BCL-2 3' untranslated region (3'UTR) was constructed to explore
      whether BCL-2 was a direct target gene of miR-181a. Real-time PCR was performed
      to test the expression of miR-181a and Bcl-2 in the selected breast cancer tissue
      samples. RESULTS: The down-regulation of miR-181a decreased adriamycin-induced
      apoptosis in MCF-7 cells. Transfected with miR-181a mimic in cells resulted in
      the decreased expression of Bcl-2. The alteration of miR-181a expression did not
      significantly affect the chemosensitivity to adriamycin in MCF-7 and MCF-7/ADR
      cells with genetic knockout of Bcl-2. miR-181a may suppress Bcl-2 expression by
      forming imperfect base pairing with the 3'UTR of Bcl-2 gene such that a negative
      relationship between miR-181a and Bcl-2 in MCF-7 and MCF-7/ADR cells is observed.
      CONCLUSIONS: At least in part, the detection of miR-181a may direct the clinical
      medication in patients with neoadjuvant chemotherapy because of miR-181a enhanced
      adriamycin-induced apoptosis via targeting Bcl-2.

PMID- 24335173
TI  - Hyperphosphorylation of tau protein in hippocampus of central insulin-resistant
      rats is associated with cognitive impairment.
AB  - BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative
      diseases. Peripheral insulin resistance increases the risk for memory impairment
      and the development of AD. OBJECTIVE: This study aims to assess changes in
      cognitive functions and the level of hyperphosphorylated tau proteins in central
      insulin-resistant rats. METHODS: An in vivo central insulin-resistant (CIR)
      animal model was generated through intracerebroventricular injection of
      streptozotocin (STZ) into insulin-resistant (IR) rats that were induced by
      feeding a high-glucose/-protein/-fat diet. The Morris water maze test was used to
      assess changes in cognitive functions, pathological changes in the cornu ammonis
      1 (CA1) region of the hippocampus were detected by immunohistochemistry, and the
      phosphorylation levels of tau proteins at specific sites were determined by
      Western blot analysis. RESULTS: The escape latency time in the Morris water maze
      test was significantly prolonged; the number of phosphorylated tau proteins in
      the CA1 region of the hippocampus was significantly increased; and the
      phosphorylation levels of tau proteins at Ser199, Thr205, Thr212, Thr217 and
      Ser396 were significantly elevated in the CIR group compared with the IR and
      control groups. CONCLUSION: This study provides direct evidence that CIR plays an
      important role in AD pathogenesis by facilitating tau hyperphosphorylation.

PMID- 24335174
TI  - Short-term hyperosmolality pretreatment on cells can reduce the radiosensitivity
      via RVI and Akt1 activation.
AB  - BACKGROUND/AIMS: The ionizing radiation (IR) has been applied in clinical
      treatment for many years and the radiosensitivity is crucial to the treatment.
      Radiosensitivity of cells is subjected to many environmental factors, such as
      hypoxia and temperature. Hyperosmolality as a common environmental factor has
      been demonstrated to be associated with survival and apoptosis of cells in many
      studies. Thus we investigated the influence of hyperosmolality on cells
      radiosensitivity. METHODS: We examined the viability and surviving fraction of L
      O2 cells of irradiated L-O2 cells, and detected the effect on AHH-1 cells by flow
      cytometry, in order to investigate the effect of short-term hyperosmolality
      pretreatment on cells radiosensitivity. Comet assay was used to assess the DNA
      strand breaks. Then the detection of Akt1 by western blot and the process of
      regulatory volume increase by CYSY-TT were involved in the mechanism. RESULT: We
      demonstrated that a short-term hyperosmolality pretreatment on cells could reduce
      their radiosensitivity. Further research indicated that the short-term hypertonic
      condition could induce regulatory volume increase (RVI), which activated Akt1 and
      degenerated the IkappaB-alpha. This process was associated with reduced cells
      radiosensitivity. Finally, we used the flufenamic acid (FFA), a blocker to cation
      channels (HICCs) to inhabit RVI and consequently inhabit the protective effect of
      hyperosmolality on irradiated cells. CONCLUSION: a short-term hyperosmolality
      pretreatment could reduce the cells radiosensitivity by RVI and following
      activation of Akt1.

PMID- 24335175
TI  - Compared analysis of LncRNA expression profiling in pdk1 gene knockout mice at
      two time points.
AB  - BACKGROUND/AIMS: Previous studies have indicated that long non-coding RNAs
      (lncRNA) are related to the occurrence and development of many human diseases,
      such as cancer and the HELLP and the brachydactyly syndromes. However, studies of
      LncRNA in heart failure have not yet been reported. Here, we investigated cardiac
      lncRNA expression profiles in the myocardial-specific knockout pdk1 gene (KO)
      mouse model of heart failure. METHODS: Cardiac samples were obtained from PDK1 KO
      and WT mice on postnatal (P) day 8 (P8) and day 40 (P40), and lncRNA expression
      profiles were analyzed by sequencing and screening using the Arraystar mouse
      lncRNA microarray. Quantitative real-time PCR analysis of these lncRNAs confirmed
      the identity of some genes. RESULTS: Comparisons of the KO and control groups
      showed fold changes of >1.5 in the expression levels of 2,024 lncRNAs at P8,
      while fold changes of >2 in the expression levels of 4,095 lncRNAs were detected
      at P40. Nineteen lncRNAs were validated by RT-PCR. Bioinformatic and pathway
      analyses indicated that mkk7, a sense overlap lncRNA, may be involved in the
      pathological processes of heart failure through the MAPK signaling pathway.
      CONCLUSION: These data reveal differentially expressed lncRNA in mice with a
      myocardial-specific deletion of the pdk1 gene, which may provide new insights
      into the mechanism of heart failure in PDK1 knockout mice.

PMID- 24335176
TI  - Effect of non-esterified fatty acids on fatty acid metabolism-related genes in
      calf hepatocytes cultured in vitro.
AB  - BACKGROUND: NEFA plays numerous roles in the metabolism of glucose, lipids, and
      proteins. A number of experimental studies have shown that NEFA may have an
      important role in fatty acid metabolism in the liver, especially in dairy cows
      that experience negative energy balance (NEB) during early lactation. METHODS: In
      this study, using fluorescent quantitative RT-PCR, ELISA, and primary hepatocytes
      cultured in vitro, we examined the effect of NEFA (0, 0.2, 0.4, 0.8, 1.6, and 3.2
      mmol/L) on fatty acid metabolism by monitoring the mRNA and protein expression of
      the following key enzymes: long chain acyl-CoA synthetase (ACSL), carnitine
      palmitoyltransferase IA (CPT IA), long chain acyl-CoA dehydrogenase (ACADL), and
      acetyl-CoA carboxylase (ACC). RESULTS: The mRNA and protein expression levels of
      ACSL and ACADL markedly increased as the concentration of NEFA in the media was
      increased. The mRNA and protein expression levels of CPT IA were enhanced
      significantly when the NEFA concentrations increased from 0 to 1.6 mmol/L and
      decreased significantly when the NEFA concentrations increased from 1.6 to 3.2
      mmol/L. The mRNA and protein expression of ACC decreased gradually with
      increasing concentrations of NEFA. CONCLUSION: These findings indicate that
      increased NEFA significantly promote the activation and beta-oxidation of fatty
      acids, but very high NEFA concentrations may inhibit the translocation of fatty
      acids into mitochondria of hepatocytes. This may explain the development of
      ketosis or liver lipidosis in dairy cows. CPT IA might be the key control enzyme
      of the fatty acid oxidation process in hepatocytes.

PMID- 24335177
TI  - The phenotypic fate of bone marrow-derived stem cells in acute kidney injury.
AB  - BACKGROUND: Despite increasing attention on the role of bone marrow derived stem
      cells in repair or rejuvenation of tissues and organs, cellular mechanisms of
      such cell-based therapy remain poorly understood. METHODS: We reconstituted
      hematopoiesis in recipient C57BL/6J mice by transplanting syngeneic GFP(+) bone
      marrow (BM) cells. Subsequently, the recipients received subcutaneous injection
      of granulocyte-colony stimulating factor (G-CSF) and were subjected to acute
      renal ischemic injury. Flow cytometry and immunostaining were performed at
      various time points to assess engraftment and phenotype of BM derived stem cells.
      RESULTS: Administration of G-CSF increased the release of BM derived stem cells
      into circulation and enhanced the ensuing recruitment of BM derived stem cells
      into injured kidney. During the second month post injury, migrated BM derived
      stem cells lost hematopoietic phenotype (CD45) but maintained the expression of
      other markers (Sca-1, CD133 and CD44), suggesting their potential of
      transdifferentiation into renal stem cells. Moreover, G-CSF treatment enhanced
      the phenotypic conversion. CONCLUSION: Our work depicted a time-course dependent
      transition of phenotypic characteristics of BM derived stem cells, demonstrated
      the existence of BM derived stem cells in damaged kidney and revealed the effects
      of G-CSF on cell transdifferentiation.

PMID- 24335178
TI  - Potential molecular mechanisms for improved prognosis and outcome with
      neoadjuvant chemotherapy prior to laparoscopical radical hysterectomy for
      patients with cervical cancer.
AB  - BACKGROUND: The p53:miR-34a:E2F positive feed-forward loop and the p53:miR
      605:Mdm2 positive feed-back loop have been identified to be crucial
      oncogenesis/tumor suppressor-regulating signaling pathways. In this study, we
      sought to examine the hypothesis that neoadjuvant chemotherapy (NAC) is a better
      approach with improved prognosis and outcomes after laparoscopical radical
      hysterectomy (LRH) on patients with cervical cancer and to elucidate the
      potential roles of the p53:miR-34a:E2F1 and the p53:miR-605:Mdm2 signaling
      pathways in this therapy. METHODS: Twenty-one patients with stage IIB cervical
      cancer were recruited to this study and they were randomly divided into two
      groups: LRH (n=10) and NAC+LRH (n=11) groups. The NAC+LRH group consisted of 4
      cycles of cisplatin, paclitaxel and carboplatin. Complication rates and NAC
      outcomes (tumor size changes, 2-year disease-free survival rate, and 2-year
      overall survival rate) were compared between the two groups. Expression of p53,
      Mdm2, E2F1, miR-34a, and miR-605 at mRNA and protein levels from the tumor
      tissues was analyzed. RESULTS: We observed that the diameter of tumors following
      chemotherapy was substantially smaller in the NAC+LRH patients than in LRH
      patients. No recurrence or metastasis after surgery was observed in the NAC+LRH
      patients, whereas 2 out of 10 LRH patients had recurrences and 1 had metastasis.
      The 2-year disease-free and overall survival rates were apparently higher in the
      NAC+LRH group than in the LRH group. Furthermore, molecular biology analyses
      revealed that the protein and mRNA levels of p53 were both markedly increased in
      patients who received NAC than those who did not, and oppositely, the levels of
      E2F1 and Mdm2 were significantly lower in the NAC+LRH patients than in the LRH
      patients. The levels of miR-34a and miR-605 were considerably higher with NAC
      relative to without NAC. Among the three anti-cancer drugs included in NAC,
      cisplatin was found to be the main component that caused increases in p53 protein
      levels, miR-34a and miR-605 miRNA levels, and decreases in Mdm2 and E2F1 protein
      levels. Furthermore, ERK1/2 inhibitor U0126 or TAB1 siRNA mitigated these changes
      induced by cisplatin. CONCLUSION: These findings not only indicate NAC as a
      rational approach for better treatment of cervical cancer with improved
      therapeutic outcomes, due partly to the ability of cisplatin to promote the
      p53:miR-34a:E2F1 positive feed-forward loop and the p53:miR-605:Mdm2 positive
      feedback loop.

PMID- 24335179
TI  - Berberine suppresses TPA-induced fibronectin expression through the inhibition of
      VEGF secretion in breast cancer cells.
AB  - BACKGROUND/AIMS: Berberine (BBR) is an isoquinoline alkaloid and is beneficial
      for the anticancer effect on a variety of human tumor cells. However, BBR's anti
      angiogenesis property and its clinical potential as an inhibitor of tumor
      angiogenesis in breast cancer cells have not been fully elucidated. Here, we
      investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well
      as VEGF-induced FN in breast cancer cells. METHODS: The secretion of VEGF protein
      was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by
      Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK,
      and CA-Akt were examined by adenovirus system. RESULTS: Our results showed that
      TPA, a tumor promoter, significantly increased the level of VEGF and FN
      expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA
      induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In
      contrast, the level of FN expression also significantly increased by
      constitutively active (CA)-AKT overexpression. We also found that TPA-induced
      VEGF and FN expression was decreased by BBR treatment. Finally, our results
      showed that VEGF augmented the expression of FN whereas VEGF-induced FN
      expression was decreased by BBR treatment. CONCLUSION: Taken together, we suggest
      that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through
      the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we
      suggest that BBR may be used as a candidate drug for the inhibition of
      angiogenesis of human breast cancer.

PMID- 24335180
TI  - Clinical study of therapeutic ocular surface medium for persistent epithelial
      defect.
AB  - PURPOSE: To investigate therapeutic ocular surface medium (TOSM), a potential
      physiological tear replacement therapy, for persistent epithelial defect (PED).
      METHODS: 11 eyes of 10 patients with PED for >= 2 weeks without improvement
      despite conventional treatment were enrolled in a prospective pilot study of TOSM
      over 1 month. RESULTS: Healing of the PED occurred in 3 out of the 11 eyes at 1,
      2 and 4 weeks, respectively. At week 4, 2 eyes were almost healed (PED area <=
      0.5 mm(2)). In 4 of the remaining 6 eyes, the PED area was reduced. Failure
      occurred in 1 case with end-stage ocular cicatricial pemphigoid and severe dry
      eye, and 1 patient withdrew due to a mild allergic reaction. There were no
      serious or irreversible side effects with TOSM. CONCLUSIONS: TOSM is a potential
      novel physiological therapy for PED that, unlike autologous serum, has the
      potential to be easily manufactured and widely available.

PMID- 24335181
TI  - Cell volume regulation and apoptotic volume decrease in rat distal colon
      superficial enterocytes.
AB  - BACKGROUND: The colon epithelium is physiologically exposed to osmotic stress,
      and the activation of cell volume regulation mechanisms is essential in
      colonocyte physiology. Moreover, colon is characterized by a high apoptotic rate
      of mature cells balancing the high division rate of stem cells. AIM: The aim of
      the present work was to investigate the main cell volume regulation mechanisms in
      rat colon surface colonocytes and their role in apoptosis. METHODS: Cell volume
      changes were measured by light microscopy and video imaging on colon explants;
      apoptosis sign appearance was monitored by confocal microscopy on annexin
      V/propidium iodide labeled explants. RESULTS: Superficial colonocytes showed a
      dynamic regulation of their cell volume during anisosmotic conditions with a
      Regulatory Volume Increase (RVI) response following hypertonic shrinkage and
      Regulatory Volume Decrease (RVD) response following hypotonic swelling. RVI was
      completely inhibited by bumetanide, while RVD was completely abolished by high
      K(+) or iberiotoxin treatment and by extracellular Ca(2+) removal. DIDS
      incubation was also able to affect the RVD response. When colon explants were
      exposed to H2O2 as apoptotic inducer, colonocytes underwent an isotonic volume
      decrease ascribable to Apoptotic Volume Decrease (AVD) within about four hours of
      exposure. AVD was shown to precede annexin V positivity. It was also inhibited by
      high K(+) or iberiotoxin treatment. Interestingly, treatment with iberiotoxin
      significantly inhibited apoptosis progression. CONCLUSIONS: In rat superficial
      colonocytes K(+) efflux through high conductance Ca(2+)-activated K(+) channels
      (BK channels) was demonstrated to be the main mechanism of RVD and to plays also
      a crucial role in the AVD process and in the progression of apoptosis.

PMID- 24335182
TI  - Heart rate recovery index in patients with psoriasis.

PMID- 24335184
TI  - How 'basal' are the basal ganglia?

PMID- 24335183
TI  - Overexpression of the pp32r1 (ANP32C) oncogene or its functional mutant
      pp32r1Y140H confers enhanced resistance to FTY720 (Finguimod).
AB  - pp32r1 (ANP32C) is oncogenic and has been shown to be overexpressed in tumors of
      the breast, prostate, and pancreas. In this work we show that pp32 family
      proteins are able to bind to the sphingosine analog FTY720 (Finguimod). Molecular
      docking studies highlight that a conserved residue F136 is likely to be a key
      determinant of the FTY720 binding site on the pp32 leucine-rich repeat domain.
      Transduction of the renal carcinoma cell line ACHN or cervical cancer cell line
      HeLa with lentivirus expressing the oncogenic family member pp32r1 or a
      pp32r1Y140H functional mutant illustrated an enhanced resistance to FTY720
      induced apoptosis. These findings highlight that certain cancers overexpressing
      pp32r1 or pp32r1 mutants are likely to demonstrate enhanced resistance to FTY720
      treatment. 

PMID- 24335185
TI  - Clinical features in association with neurodegenerative diseases and
      malignancies.
AB  - OBJECTIVE: To examine whether there are clinical features in Japanese patients
      with both neurodegenerative diseases and cancers. METHODS: We analyzed the
      clinical characteristics of consecutive Japanese patients with neurodegenerative
      diseases during the past 5 years, including amyotrophic lateral sclerosis (ALS),
      Parkinson's disease (PD), dementia with Lewy bodies, progressive supranuclear
      palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA).
      RESULTS: Out of 292 patients, 39 patients had cancers, including a past history,
      as follows: ALS, n = 16; PD, n = 8; PSP, n = 7; CBD, n = 1, and MSA, n = 7. About
      10% of patients with neurodegenerative diseases developed cancer after onset of
      the disease; about 30% of patients with ALS, PD, or PSP occurring with cancers
      died of cancer. Gastric cancer was most common before the onset of ALS (62.5%)
      but did not develop after the onset of ALS. Conversely, PD patients frequently
      developed gastric cancers after the onset of neurological signs (60.0%) in spite
      of no cancer before the onset of PD. The proportion of breast cancer in MSA
      (45.5%) was significantly higher than in other neurodegenerative diseases.
      CONCLUSION: ALS, PD, or MSA patients with cancer showed clinical characteristics
      unique to each neurodegenerative disease in Japan compared to other countries.

PMID- 24335186
TI  - Thelytoky and sex determination in the hymenoptera: mutual constraints.
AB  - The Hymenoptera show a high propensity for transitions from arrhenotokous
      reproduction (diploid females develop from fertilized eggs, haploid males from
      unfertilized eggs) to thelytokous reproduction (diploid females develop from
      unfertilized eggs). However, the evolution of thelytoky is frequently constrained
      by the sex determination system. Under the ancestral system, complementary sex
      determination (CSD), the constraint results from the production of diploid males
      by thelytokous females. The magnitude of this constraint depends on the
      cytological mechanism of thelytoky, determining the rate at which thelytokous
      lines lose heterozygosity and on whether a single locus or multiple loci are
      involved in CSD. In this review, it is discussed how diploid male production in
      the case of CSD or other constraints in the case of alternative sex determination
      systems may impede transitions to thelytoky, but it is also shown that under
      particular (and presumably rare) circumstances the production of diploid males
      will promote rather than hamper the evolution of thelytoky. Furthermore,
      constraints between the evolution of thelytoky and sex determination may be
      mutual, because once thelytoky has evolved, it can impact on sex determination.
      Finally, researchers are encouraged to exploit the frequent occurrence of
      thelytoky as an opportunity to learn more about the mechanisms of sex
      determination in the Hymenoptera.

PMID- 24335187
TI  - Variola virus E3L Zalpha domain, but not its Z-DNA binding activity, is required
      for PKR inhibition.
AB  - Responding to viral infection, the interferon-induced, double-stranded RNA
      (dsRNA)-activated protein kinase PKR phosphorylates translation initiation factor
      eIF2alpha to inhibit cellular and viral protein synthesis. To overcome this host
      defense mechanism, many poxviruses express the protein E3L, containing an N
      terminal Z-DNA binding (Zalpha) domain and a C-terminal dsRNA-binding domain
      (dsRBD). While E3L is thought to inhibit PKR activation by sequestering dsRNA
      activators and by directly binding the kinase, the role of the Zalpha domain in
      PKR inhibition remains unclear. Here, we show that the E3L Zalpha domain is
      required to suppress the growth-inhibitory properties associated with expression
      of human PKR in yeast, to inhibit PKR kinase activity in vitro, and to reverse
      the inhibitory effects of PKR on reporter gene expression in mammalian cells
      treated with dsRNA. Whereas previous studies revealed that the Z-DNA binding
      activity of E3L is critical for viral pathogenesis, we identified point mutations
      in E3L that functionally uncouple Z-DNA binding and PKR inhibition. Thus, our
      studies reveal a molecular distinction between the nucleic acid binding and PKR
      inhibitory functions of the E3L Zalpha domain, and they support the notion that
      E3L contributes to viral pathogenesis by targeting PKR and other components of
      the cellular anti-viral defense pathway. 

PMID- 24335189
TI  - Beyond linear methods of data analysis: time series analysis and its applications
      in renal research.
AB  - Analysis of temporal trends in medicine is needed to understand normal physiology
      and to study the evolution of disease processes. It is also useful for monitoring
      response to drugs and interventions, and for accountability and tracking of
      health care resources. In this review, we discuss what makes time series analysis
      unique for the purposes of renal research and its limitations. We also introduce
      nonlinear time series analysis methods and provide examples where these have
      advantages over linear methods. We review areas where these computational methods
      have found applications in nephrology ranging from basic physiology to health
      services research. Some examples include noninvasive assessment of autonomic
      function in patients with chronic kidney disease, dialysis-dependent renal
      failure and renal transplantation. Time series models and analysis methods have
      been utilized in the characterization of mechanisms of renal autoregulation and
      to identify the interaction between different rhythms of nephron pressure flow
      regulation. They have also been used in the study of trends in health care
      delivery. Time series are everywhere in nephrology and analyzing them can lead to
      valuable knowledge discovery. The study of time trends of vital signs, laboratory
      parameters and the health status of patients is inherent to our everyday clinical
      practice, yet formal models and methods for time series analysis are not fully
      utilized. With this review, we hope to familiarize the reader with these
      techniques in order to assist in their proper use where appropriate.

PMID- 24335188
TI  - Enhanced eIF1 binding to the 40S ribosome impedes conformational rearrangements
      of the preinitiation complex and elevates initiation accuracy.
AB  - In the current model of translation initiation by the scanning mechanism, eIF1
      promotes an open conformation of the 40S subunit competent for rapidly loading
      the eIF2.GTP.Met-tRNAi ternary complex (TC) in a metastable conformation (POUT)
      capable of sampling triplets entering the P site while blocking accommodation of
      Met-tRNAi in the PIN state and preventing completion of GTP hydrolysis (Pi
      release) by the TC. All of these functions should be reversed by eIF1
      dissociation from the preinitiation complex (PIC) on AUG recognition. We tested
      this model by selecting eIF1 Ssu(-) mutations that suppress the elevated UUG
      initiation and reduced rate of TC loading in vivo conferred by an eIF1 (Sui(-))
      substitution that eliminates a direct contact of eIF1 with the 40S subunit.
      Importantly, several Ssu(-) substitutions increase eIF1 affinity for 40S subunits
      in vitro, and the strongest-binding variant (D61G), predicted to eliminate ionic
      repulsion with 18S rRNA, both reduces the rate of eIF1 dissociation and
      destabilizes the PIN state of TC binding in reconstituted PICs harboring Sui(-)
      variants of eIF5 or eIF2. These findings establish that eIF1 dissociation from
      the 40S subunit is required for the PIN mode of TC binding and AUG recognition
      and that increasing eIF1 affinity for the 40S subunit increases initiation
      accuracy in vivo. Our results further demonstrate that the GTPase-activating
      protein eIF5 and beta-subunit of eIF2 promote accuracy by controlling eIF1
      dissociation and the stability of TC binding to the PIC, beyond their roles in
      regulating GTP hydrolysis by eIF2. 

PMID- 24335190
TI  - Effects of pulmonary artery perfusion with urinary trypsin inhibitor as a lung
      protective strategy under hypothermic low-flow cardiopulmonary bypass in an
      infant piglet model.
AB  - OBJECTIVE: This study aimed to evaluate the effects of pulmonary artery perfusion
      with a urinary trypsin inhibitor (UTI) as a lung protective strategy in order to
      provide an experimental basis for immature lung clinical protective strategies on
      deep hypothermia with low-flow (DHLF) cardiopulmonary bypass (CPB)-induced
      pulmonary injury in an infant piglet model. METHODS: The piglets (n=15), aged
      18.7+/-0.3 days, weight 4.48+/-0.21kg, were randomly divided into 3 groups, with
      5 piglets in each group: the control group, the pulmonary artery perfusion
      without UTI group (Group P) and the pulmonary artery perfusion with UTI group
      (Group U). The levels of the cytokines tumour necrosis factor-alpha,
      myeloperoxidase, malondialdehyde and interleukin-10 (TNF-alpha, MPO, MDA and IL
      10) in pulmonary venous serum and lung tissue and the activity of NF-kappa B in
      lung tissue were measured by enzyme-linked immunosorbent assay (ELISA) and
      electrophoresis mobility shift assay (EMSA), respectively. RESULTS: After DHLF
      CPB, all of the piglets demonstrated a state of lung injury as a deterioration of
      lung function indices, lung injury scores, pulmonary ultrastructure changes,
      expression of TNF-alpha, MPO, MDA and IL-10 and the activities of nuclear factor
      kappa B (NF-kappaB), while pulmonary artery perfusion with UTI significantly
      ameliorated lung function and histopathological changes, with greatly decreased
      serum levels of TNF-alpha and MPO compared to the other two groups. Also, we
      found an increase in the level of IL-10 in Group U lungs compared with that in
      Group P lungs, which correlated with a strong inhibition in the activity of NF
      kappaB. CONCLUSION: Pulmonary artery perfusion with UTI ameliorated the DHLF
      induced immature pulmonary injury in the lungs via a reduction of pro
      inflammatory cytokine expression and up-regulated levels of IL-10 by inhibiting
      the activity of NF-kappaB.

PMID- 24335191
TI  - High-dose topical bevacizumab for corneal neovascularization.
AB  - BACKGROUND/AIMS: Bevacizumab (Avastin), an anti-vascular endothelial growth
      factor drug, has been successfully used in the recent years to treat ocular
      pathologies, mostly by intravitreal administration. The aim of the current study
      was to assess the off-label topical use of high-dose bevacizumab for the
      treatment of corneal neovascularization. METHODS: Seventeen eyes of 17 patients
      with corneal neovascularization secondary to various pathologies were included.
      The patients were treated with topical bevacizumab (25 mg/ml) 4 times daily for 2
      weeks. The following parameters were evaluated at baseline and on days 3, 7 and
      14: visual acuity, slit-lamp examination, intraocular pressure, heart rate and
      blood pressure. Color photos were obtained at baseline and on day 14. RESULTS:
      Eleven eyes (65%) demonstrated regression of corneal neovascularization and/or
      clearing of corneal opacification. Adverse ocular events were mild and transient,
      and included eyelid swelling/chalazion and superficial punctate keratitis.
      CONCLUSION: Treatment with high-dose topical bevacizumab (25 mg/ml) was effective
      for corneal neovascularization in nearly two thirds of the eyes treated. Adverse
      ocular side effects were mild and transient.

PMID- 24335192
TI  - EZH2 participates in malignant biological behavior of epithelial ovarian cancer
      through regulating the expression of BRCA1.
AB  - Aberrant overexpression of the enhancer of zeste homolog 2 (EZH2), a histone
      methyltransferase inhibiting targets expression via epigenetic mechanisms, is
      associated with an invasive phenotype and drug resistance in ovarian cancer.
      Breast cancer 1 (BRCA1) gene is a well-recognized tumor suppressor, whose
      downregulation plays a key role in the development of ovarian cancer. In the
      present study, we found depletion of EZH2 increased BRCA1 protein expression and
      promoted its nuclear translocation, but decreased BRCA1 mRNA expression.
      Treatment with the Akt-1 activator insulin-like growth factor-1 (IGF-1) prevented
      EZH2-induced BRCA1 nuclear/cytoplasmic shuttling. Loss of BRCA1 partially rescued
      the effects of EZH2 downregulation on proliferation, G 2/M transition, and
      migration in ovarian cancer cells. However, in a cisplatin-resistant sub-line of
      A2780 (A2780/DDP), both EZH2 and BRCA1 were overexpressed compared with parental
      A2780 cells and depletion of EZH2 reduced BRCA1 expression at both mRNA and
      protein levels. Downregulation of EZH2 or BRCA1 sensitized A2780/DDP cells to
      cisplatin, whereas simultaneous inhibition of them only resulted in modest
      resensitization instead of showing any synergistic effect because EZH2 expression
      was reactivated when BRCA1 expression was very low. Accordingly, our results
      suggest the expression of BRCA1 is modulated by EZH2 in epithelial ovarian cancer
      and BRCA1 is required for the effects of EZH2 downregulation on biological
      behaviors of tumor cells. 

PMID- 24335194
TI  - Purinergic signaling and blood vessels in health and disease.
AB  - Purinergic signaling plays important roles in control of vascular tone and
      remodeling. There is dual control of vascular tone by ATP released as a
      cotransmitter with noradrenaline from perivascular sympathetic nerves to cause
      vasoconstriction via P2X1 receptors, whereas ATP released from endothelial cells
      in response to changes in blood flow (producing shear stress) or hypoxia acts on
      P2X and P2Y receptors on endothelial cells to produce nitric oxide and
      endothelium-derived hyperpolarizing factor, which dilates vessels. ATP is also
      released from sensory-motor nerves during antidromic reflex activity to produce
      relaxation of some blood vessels. In this review, we stress the differences in
      neural and endothelial factors in purinergic control of different blood vessels.
      The long-term (trophic) actions of purine and pyrimidine nucleosides and
      nucleotides in promoting migration and proliferation of both vascular smooth
      muscle and endothelial cells via P1 and P2Y receptors during angiogenesis and
      vessel remodeling during restenosis after angioplasty are described. The
      pathophysiology of blood vessels and therapeutic potential of purinergic agents
      in diseases, including hypertension, atherosclerosis, ischemia, thrombosis and
      stroke, diabetes, and migraine, is discussed. 

PMID- 24335195
TI  - HIF1alpha genetic variants and protein expressions determine the response to
      platinum based chemotherapy and clinical outcome in patients with advanced NSCLC.
AB  - AIM: To investigate whether the hypoxia-inducible factor-1alpha (HIF-1alpha)
      genetic variants and protein expression affect the chemotherapy response and the
      clinical outcome of patients with advanced non-small cell lung cancer (NSCLC).
      METHODS: A total of 741 patients with histologically confirmed advanced NSCLC
      were recruited. Two polymorphisms of HIF-1alpha gene, namely, the C1772T (P582S)
      and G1790A (A588T) polymorphisms were determined. The HIF-1alpha protein
      expression was determined in 162 different biopsy samples by
      immunohistochemistry. RESULTS: All patients received platinum-based chemotherapy,
      311 were chemotherapy responders and 430 were non-responders. The 1772 CC
      genotype carriers had a higher chance to be chemotherapy responders compared with
      those carrying the TT genotype. Patients with high HIF-1alpha expressions had a
      significantly higher chance to be non-responder to chemotherapy than those with
      low HIF-1alpha expressions. The patients with 1772CC had markedly longer overall
      survival (OS) and progression free survival (PFS) than those carrying the 1772CT
      and 1772TT genotype. The HIF-1alpha expression level was significantly related to
      the OS, but not PFS. CONCLUSION: The results of our study suggest that HIF1alpha
      genetic variants and protein expression may be used as marker to screen NSCLC
      patients who are more likely to be responder to platinum based chemotherapy.

PMID- 24335193
TI  - Neuroinflammation and comorbidity of pain and depression.
AB  - Comorbid depression and chronic pain are highly prevalent in individuals
      suffering from physical illness. Here, we critically examine the possibility that
      inflammation is the common mediator of this comorbidity, and we explore the
      implications of this hypothesis. Inflammation signals the brain to induce
      sickness responses that include increased pain and negative affect. This is a
      typical and adaptive response to acute inflammation. However, chronic
      inflammation induces a transition from these typical sickness behaviors into
      depression and chronic pain. Several mechanisms can account for the high
      comorbidity of pain and depression that stem from the precipitating inflammation
      in physically ill patients. These mechanisms include direct effects of cytokines
      on the neuronal environment or indirect effects via downregulation of G protein
      coupled receptor kinase 2, activation of the tryptophan-degrading enzyme
      indoleamine 2,3-dioxygenase that generates neurotropic kynurenine metabolites,
      increased brain extracellular glutamate, and the switch of GABAergic
      neurotransmission from inhibition to excitation. Despite the existence of many
      neuroimmune candidate mechanisms for the co-occurrence of depression and chronic
      pain, little work has been devoted so far to critically assess their mediating
      role in these comorbid symptoms. Understanding neuroimmune mechanisms that
      underlie depression and pain comorbidity may yield effective pharmaceutical
      targets that can treat both conditions simultaneously beyond traditional
      antidepressants and analgesics. 

PMID- 24335196
TI  - Heart rate recovery is impaired in patients with psoriasis.

PMID- 24335197
TI  - Tumor volume as a prognostic factor in resectable malignant melanoma.
AB  - BACKGROUND: Vertical tumor thickness according to Breslow and histological
      ulceration are still the most powerful predictors for the clinical outcome of
      resectable cutaneous malignant melanoma (MM) without lymph node infiltration. It
      has been proposed that tumor volume in MM may also be of prognostic relevance.
      METHODS: We retrospectively analyzed the prognostic impact of tumor volume and
      other established risk factors in 122 MM patients with a median follow-up period
      of 39.7 months. RESULTS: We found the logarithmic tumor volume to be a better
      prognostic factor compared to Breslow tumor thickness in multivariate analysis.
      MM with a tumor volume below a threshold of 140 mm(3) had a significantly higher
      relapse-free survival after 5 years of 98% compared to 47% in larger MMs (p <
      0.0001). CONCLUSION: In some melanomas with a low tumor thickness, a higher tumor
      volume appeared to be linked to a higher risk of disease recurrence. Inclusion of
      tumor volume into the risk assessment of resectable MM may be of benefit in the
      future.

PMID- 24335198
TI  - Brief screening for mild cognitive impairment in subcortical ischemic vascular
      disease: a comparison study of the Montreal Cognitive Assessment with the Mini
      Mental State Examination.
AB  - BACKGROUND AND PURPOSE: To assess the validity of the Montreal Cognitive
      Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in the detection
      of vascular mild cognitive impairment (VaMCI) in patients with subcortical
      ischemic vascular disease (SIVD). METHODS: Among 102 SIVD patients, both cutoff
      scores of the MMSE and MoCA for differentiating VaMCI from no cognitive
      impairment (NCI) or differentiating VaMCI from vascular dementia (VaD) were
      determined by the receiver operator characteristic (ROC) analysis. Optimal
      sensitivity with specificity of cutoff scores was obtained after the raw scores
      were adjusted for education. RESULTS: After adjusting for education, the MoCA
      cutoff score for differentiating VaMCI from NCI was at 24/25 and that for
      differentiating VaMCI from VaD was at 18/19. After applying the adjusted MoCA
      scores from 19 to 24 to identify VaMCI in all SIVD patients, sensitivity was at
      76.7% and specificity was at 81.4% (kappa = 0.579). The adjusted cutoff score of
      the MMSE for differentiating VaMCI from NCI was at 28/29 and that for
      differentiating VaMCI from VaD was at 25/26. The sensitivity and specificity of
      the adjusted MMSE was at 58.1 and 71.2%, respectively, when using the score from
      26 to 28 to identify VaMCI in SIVD patients (kappa = 0.294). CONCLUSIONS: The
      MoCA detected subcortical VaMCI better than the MMSE.

PMID- 24335199
TI  - Effect of in utero exposure to antiepileptic drugs on cognitive function in
      children.
AB  - Epilepsy, being one of the most common neurological disorders, has raised
      concerns in developed and developing countries. Due to its heterogeneous
      pathophysiology and different cellular, molecular and genetic mechanisms, it is
      becoming a threat worldwide. Despite wide availability of antiepileptic drugs
      (AEDs), epilepsy still remains a major cause of morbidity and mortality among the
      pediatric and geriatric populations. Commonly available AED therapies include
      sodium and calcium channel blockers, GABA agonists, and potassium channel
      activists. Along with beneficial effects, AEDs have been known to cause
      teratogenic responses, learning disabilities, malfunctions of different organs,
      and drug-induced syndrome. Nowadays, AED-related cognitive impairment is emerging
      as a serious condition, affecting children born to epileptic women.

PMID- 24335200
TI  - TMPRSS4 correlates with colorectal cancer pathological stage and regulates cell
      proliferation and self-renewal ability.
AB  - Transmembrane protease/serine 4 (TMPRSS4) is a member of the type II
      transmembrane serine protease (TTSP) family and it was found highly expressed in
      several cancers. This study aims to evaluate the expression of TMPRSS4 in
      colorectal cancer (CRC) and investigate its role in proliferation and self
      renewal of colon cancer cells. qRT-PCR and immunohistochemistry were used to
      detect the mRNA and protein expression level of TMRPSS4 in CRC samples
      respectively. Loss of function assay was conducted with RNAi technique. Cell
      proliferation was done with WST-8 assay; cell apoptosis and cell cycle analysis
      were performed with flow cytometry; invasion and migration were done with
      transwell assay. Plate and soft agarose clonogenic assays were used to detect
      clone-formation ability. CD44 and CD133 expressions were analyzed by flow
      cytometry and western blot. We found that TMPRSS4 was highly expressed in CRC
      tissues both at mRNA and protein level and correlated with pathological stage.
      Knockdown of TMPRSS4 in highly expressed colon cancer cell line HCT116 resulted
      in inhibition of cell proliferation, induction of cell apoptosis and suppression
      of invasion and migration; moreover, knockdown of TMPRSS4 suppressed the in vitro
      clone-formation ability of HCT116 and reduced the expressions of CD44 and CD133.
      The findings in this research showed that TMPRSS4 was associated with CRC stage
      and regulated the proliferation and self-renewal ability of colon cancer cells;
      TMRPSS4 was involved in the development and progression of CRC. 

PMID- 24335201
TI  - The role of complement in age-related macular degeneration: heparan sulphate, a
      ZIP code for complement factor H?
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in
      developed nations and has been associated with complement dysregulation in the
      central retina. The Y402H polymorphism in the complement regulatory protein
      factor H (CFH) can confer a >5-fold increased risk of developing AMD and is
      present in approximately 30% of people of European descent. CFH, in conjunction
      with other factors, regulates complement activation in host tissues, and the
      Y402H polymorphism has been found to alter the protein's specificity for heparan
      sulphate (HS) - a complex polysaccharide found ubiquitously in mammals. HS, which
      is present on the cell surface and also in the extracellular matrix, exhibits
      huge structural diversity due to variations in the level/pattern of sulphation,
      where particular structures may act as 'ZIP codes' for different tissue/cellular
      locations. Recent work has demonstrated that CFH contains two HS-binding domains
      that each recognize specific HS ZIP codes, allowing differential recognition of
      Bruch's membrane (in the eye) or the glomerular basement membrane (in the
      kidney). Importantly, the Y402H polymorphism impairs the binding of CFH to the HS
      in Bruch's membrane, which could result in increased complement activation and
      chronic local inflammation (in 402H individuals) and thereby contribute to AMD
      pathology.

PMID- 24335202
TI  - Protective effects of bone marrow-derived endothelial progenitor cells and
      Houttuynia cordata in lipopolysaccharide-induced acute lung injury in rats.
AB  - BACKGROUND/AIMS: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS)
      is a serious health problem, and an effective treatment is needed for use in the
      clinical setting. METHODS: In this study, we first constructed ALI models in
      Adult Sprague-Dawley rats. We then used an herbal medicine, Houttuynia cordata
      (HC), to enhance the effect of endothelial progenitor cells (EPCs) on ALI.
      RESULTS: (1) HC improved the therapeutic effects of EPCs on lipopolysachharide
      induced ALI in the rat model; (2) HC down-regulated the anti-inflammatory
      response by suppressing inflammatory cytokines; (3) the combination of EPC and HC
      reduced expression of iNOS and ET-1 and subsequently prevented lung injury.
      CONCLUSION: Combined EPC and HC therapy was more effective than either therapy
      alone. EPC and HC could be used in the clinical treatment of ALI.

PMID- 24335203
TI  - Pityriasis rosea in a hepatitis B-positive patient treated with pegylated
      interferon alpha2a: report of a case and review of the literature.
AB  - Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease caused by
      the endogenous reactivation of human herpesvirus (HHV)-6 and/or HHV-7 infection
      in conditions of altered immunity. In addition, many drugs have been incriminated
      as possible triggers of PR-like eruptions, characterized by clinical,
      morphological and histopathological features that differ from typical PR. Here,
      we report a case of PR in a patient with chronic hepatitis B, receiving pegylated
      interferon alpha2a (PEG-IFN-alpha2a). PR, arising after the second administration
      of the PEG-IFN-alpha2a, might be considered a clinical expression of the
      patient's altered immune condition as reported in the immune reconstitution
      inflammatory syndrome affecting patients with human immunodeficiency virus
      infection after high-dose antiretroviral therapy.

PMID- 24335204
TI  - Analysis of the intestinal microbiome of a recovered Clostridium difficile
      patient after fecal transplantation.
AB  - BACKGROUND: Clostridium difficile infections upon antibiotic disruption of the
      gut microbiota are potentially lethal. Fecal microbiota transplantation (FMT) is
      a promising treatment option for recurrent C. difficile-associated disease
      (CDAD). Here, we present a patient with recurrent CDAD that received FMT, leading
      to full recovery for what has now been 3 years. We performed metagenomic
      sequencing on stool samples to assess if there are indications for recolonization
      with C. difficile and changes in the gut microbiota after FMT. METHODS: DNA from
      the stool of the donor and recipient was subjected to illumina sequencing.
      Obtained read sets were assembled to contiguous sequences and open reading frames
      were predicted. Deduced proteins were taxonomically assigned. RESULTS: We
      detected complex and apparently healthy microbiomes in the donor's and
      recipient's intestines after FMT, but no indications for C. difficile
      colonization. CONCLUSIONS: Metagenomic analysis proved suitable to analyze the
      intestinal microbiome after FMT. Discussion of our evaluation procedure and data
      management may be helpful for future studies. We demonstrated restoration of a
      healthy and diverse gut microbiome with chimeric composition from donor and
      recipient, and long-lasting clearance of C. difficile. The procedure is simple,
      cheap, caused no side effects, and was stable over 3 years.

PMID- 24335205
TI  - Iron toxicity in hematopoietic stem cell transplantation: Strike while the iron
      is labile.

PMID- 24335206
TI  - Increase in heterogeneity of biceps brachii activation during isometric
      submaximal fatiguing contractions: a multichannel surface EMG study.
AB  - The effects of fatigue emerge from the beginning of sustained submaximal
      contractions, as shown by an increase in the amplitude of the surface
      electromyogram (EMG). The increase in EMG amplitude is attributed to an
      augmentation of the excitatory drive to the motor neuron pool that, more
      importantly than increasing discharge rates, recruits additional motor units for
      the contraction. The aim of this study was to determine whether the
      spatiotemporal distribution of biceps brachii (BB) activity becomes more or less
      heterogeneous during a fatiguing isometric contraction sustained at a submaximal
      target force. Multiple electrodes were attached over the entire BB muscle, and
      principal component analysis (PCA) was used to extract the representative
      information from multiple monopolar EMG channels. The development of
      heterogeneity during the fatiguing contraction was quantified by applying a
      cluster algorithm on the PCA-processed EMG amplitudes. As shown previously, the
      overall EMG amplitude increased during the sustained contraction, whereas there
      was no change in coactivation of triceps brachii. However, EMG amplitude did not
      increase in all channels and even decreased in some. The change in spatial
      distribution of muscle activity varied across subjects. As found in other
      studies, the spatial distribution of EMG activity changed during the sustained
      contraction, but the grouping and size of the clusters did not change. This study
      showed for the first time that muscle activation became more heterogeneous during
      a sustained contraction, presumably due to a decrease in the strength of common
      inputs with the recruitment of additional motor units. 

PMID- 24335207
TI  - Gradual mechanics-dependent adaptation of medial gastrocnemius activity during
      human walking.
AB  - While performing a simple bouncing task, humans modify their preferred movement
      period and pattern of plantarflexor activity in response to changes in system
      mechanics. Over time, the preferred movement pattern gradually adapts toward the
      resonant frequency. The purpose of the present experiments was to determine
      whether humans undergo a similar process of gradually adapting their stride
      period and plantarflexor activity after a change in mechanical demand while
      walking. Participants walked on a treadmill while we measured stride period and
      plantarflexor activity (medial gastrocnemius and soleus). Plantarflexor activity
      during stance was divided into a storage phase (30-65% stance) and a return phase
      (65-100% stance) based on when the Achilles tendon has previously been shown to
      store and return mechanical energy. Participants walked either on constant
      inclines (0%, 1%, 5%, 9%) or on a variable incline (0-1%) for which they were
      unaware of the incline changes. For variable-incline trials, participants walked
      under both single-task and dual-task conditions in order to vary the cognitive
      load. Both stride period and plantarflexor activity increased at steeper
      inclines. During single-task walking, small changes in incline were followed by
      gradual adaptation of storage-phase medial gastrocnemius activity. However, this
      adaptation was not present during dual-task walking, indicating some level of
      cognitive involvement. The observed adaptation may be the result of using
      afferent feedback in order to optimize the contractile conditions of the
      plantarflexors during the stance phase. Such adaptation could serve to improve
      metabolic economy but may be limited in clinical populations with disrupted
      proprioception. 

PMID- 24335208
TI  - Neuronal interaural level difference response shifts are level-dependent in the
      rat auditory cortex.
AB  - How does the brain accomplish sound localization with invariance to total sound
      level? Sensitivity to interaural level differences (ILDs) is first computed at
      the lateral superior olive (LSO) and is observed at multiple levels of the
      auditory pathway, including the central nucleus of inferior colliculus (ICC) and
      auditory cortex. In LSO, this ILD sensitivity is level-dependent, such that ILD
      response functions shift toward the ipsilateral (excitatory) ear with increasing
      sound level. Thus early in the processing pathway changes in firing rate could
      indicate changes in sound location, sound level, or both. In ICC, while ILD
      responses can shift toward either ear in individual neurons, there is no net ILD
      response shift at the population level. In behavioral studies of human sound
      localization acuity, ILD sensitivity is invariant to increasing sound levels.
      Level-invariant sound localization would suggest transformation in level
      sensitivity between LSO and perception of sound sources. Whether this
      transformation is completed at the level of the ICC or continued at higher levels
      remains unclear. It also remains unknown whether perceptual sound localization is
      level-invariant in rats, as it is in humans. We asked whether ILD sensitivity is
      level-invariant in rat auditory cortex. We performed single-unit and whole cell
      recordings in rat auditory cortex under ketamine anesthesia and measured
      responses to white noise bursts presented through sealed earphones at a range of
      ILDs. Surprisingly, we found that with increasing sound levels ILD responses
      shifted toward the ipsilateral ear (which is typically inhibitory), regardless of
      whether cells preferred ipsilateral, contralateral, or binaural stimuli. Voltage
      clamp recordings suggest that synaptic inhibition does not contribute
      substantially to this transformation in level sensitivity. We conclude that the
      level invariance of ILD sensitivity seen in behavioral studies is not present in
      rat auditory cortex. 

PMID- 24335209
TI  - A new method for piercing the tentorium cerebelli for implanting fragile
      electrodes into the brain stem in the rhesus monkey (Macaca mulatta).
AB  - Recent developments in neuron recording techniques include the invention of some
      fragile electrodes. The fragility of these electrodes impedes their successful
      use in deep brain recordings because it is difficult to penetrate the electrodes
      through the dura mater, especially the tentorium cerebelli (TC) enclosing the
      cerebellum and brain stem. This paper reports a new method to pierce the TC for
      inserting fragile electrodes into the inferior colliculus of rhesus monkeys.
      Briefly, a unique tool kit, consisting of needles with sharp tips, a guide tube
      and an "impactor," was used in a multistep protocol to pierce the TC. The
      impactor provided a brief force that quickly thrusts the needles through the
      meninges without causing significant damage to the brain tissue under the TC.
      Using this novel approach, tetrodes were successfully implanted into the inferior
      colliculus of a rhesus monkey and neuronal discharge signals were recorded. This
      method, which is simple, convenient and economical, allows neurophysiologists to
      study the electrophysiological characteristics of deep brain structures under the
      TC with advanced, albeit fragile, electrodes. 

PMID- 24335210
TI  - Fluorescent imaging reports an extracellular alkalinization induced by
      glutamatergic activation of isolated retinal horizontal cells.
AB  - Extracellular acidification induced by retinal horizontal cells has been
      hypothesized to underlie lateral feedback inhibition onto vertebrate
      photoreceptors. To test this hypothesis, the H(+)-sensitive fluorophore 5
      hexadecanoylaminofluorescein (HAF) was used to measure changes in H(+) from
      horizontal cells isolated from the retina of the catfish. HAF staining conditions
      were modified to minimize intracellular accumulation of HAF and maximize membrane
      associated staining, and ratiometric fluorescent imaging of cells displaying
      primarily membrane-associated HAF fluorescence was conducted. Challenge of such
      HAF-labeled cells with glutamate or the ionotropic glutamate receptor agonist
      kainate produced an increase in the fluorescence ratio, consistent with an
      alkalinization response of +0.12 pH units and +0.23 pH units, respectively. This
      alkalinization was blocked by the AMPA receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), the L-type calcium channel blocker nifedipine,
      and lanthanum. The alkalinization reported by HAF was consistent with
      extracellular alkalinizations detected in previous studies using self-referencing
      H(+)-selective microelectrodes. The spatial distribution of the kainate-induced
      changes in extracellular H(+) was also examined. An overall global alkalinization
      around the cell was observed, with no obvious signs of discrete centers of
      acidification. Taken together, these data argue against the hypothesis that
      glutamatergic-induced efflux of protons from horizontal cells mediates lateral
      feedback inhibition in the outer retina. 

PMID- 24335211
TI  - Synaptic modulation and inward current produced by oxytocin in substantia
      gelatinosa neurons of adult rat spinal cord slices.
AB  - Cellular mechanisms for antinociception produced by oxytocin in the spinal dorsal
      horn have not yet been investigated thoroughly. We examined how oxytocin affects
      synaptic transmission in substantia gelatinosa neurons, which play a pivotal role
      in regulating nociceptive transmission, by applying the whole-cell patch-clamp
      technique to the substantia gelatinosa neurons of adult rat spinal cord slices.
      Bath-applied oxytocin did not affect glutamatergic spontaneous, monosynaptically
      evoked primary-afferent Adelta-fiber and C-fiber excitatory transmissions. On the
      other hand, oxytocin produced an inward current at -70 mV and enhanced GABAergic
      and glycinergic spontaneous inhibitory transmissions. These activities were
      repeated with a slow recovery from desensitization, concentration-dependent and
      mimicked by oxytocin-receptor agonist. The oxytocin current was inhibited by
      oxytocin-receptor antagonist, intracellular GDPbetaS, U-73122, 2
      aminoethoxydiphenyl borate, but not dantrolene, chelerythrine, dibutyryl cyclic
      AMP, CNQX, Ca(2+)-free and tetrodotoxin, while the spontaneous inhibitory
      transmission enhancements were depressed by tetrodotoxin. Current-voltage
      relation for the oxytocin current reversed at negative potentials more than the
      equilibrium potential for K(+), or around 0 mV. The oxytocin current was
      depressed in high-K(+), low-Na(+) or Ba(2+)-containing solution. Vasopressin V1A
      receptor antagonist inhibited the oxytocin current, but there was no correlation
      in amplitude between a vasopressin-receptor agonist [Arg(8)]vasopressin and
      oxytocin responses. It is concluded that oxytocin produces a membrane
      depolarization mediated by oxytocin but not vasopressin-V1A receptors, which
      increases neuronal activity, resulting in the enhancement of inhibitory
      transmission, a possible mechanism for antinociception. This depolarization is
      due to a change in membrane permeabilities to K(+) and/or Na(+), which is
      possibly mediated by phospholipase C and inositol 1,4,5-triphosphate-induced
      Ca(2+)-release. 

PMID- 24335213
TI  - Neuromodulation of evoked muscle potentials induced by epidural spinal-cord
      stimulation in paralyzed individuals.
AB  - Epidural stimulation (ES) of the lumbosacral spinal cord has been used to
      facilitate standing and voluntary movement after clinically motor-complete spinal
      cord injury. It seems of importance to examine how the epidurally evoked
      potentials are modulated in the spinal circuitry and projected to various motor
      pools. We hypothesized that chronically implanted electrode arrays over the
      lumbosacral spinal cord can be used to assess functionally spinal circuitry
      linked to specific motor pools. The purpose of this study was to investigate the
      functional and topographic organization of compound evoked potentials induced by
      the stimulation. Three individuals with complete motor paralysis of the lower
      limbs participated in the study. The evoked potentials to epidural spinal
      stimulation were investigated after surgery in a supine position and in one
      participant, during both supine and standing, with body weight load of 60%. The
      stimulation was delivered with intensity from 0.5 to 10 V at a frequency of 2 Hz.
      Recruitment curves of evoked potentials in knee and ankle muscles were collected
      at three localized and two wide-field stimulation configurations. Epidural
      electrical stimulation of rostral and caudal areas of lumbar spinal cord resulted
      in a selective topographical recruitment of proximal and distal leg muscles, as
      revealed by both magnitude and thresholds of the evoked potentials. ES activated
      both afferent and efferent pathways. The components of neural pathways that can
      mediate motor-evoked potentials were highly dependent on the stimulation
      parameters and sensory conditions, suggesting a weight-bearing-induced
      reorganization of the spinal circuitries. 

PMID- 24335212
TI  - BDNF-endocannabinoid interactions at neocortical inhibitory synapses require
      phospholipase C signaling.
AB  - Endogenous cannabinoids (endocannabinoids) and neurotrophins, particularly brain
      derived neurotrophic factor (BDNF), are potent synaptic modulators that are
      expressed throughout the forebrain and play critical roles in many behavioral
      processes. Although the effects of BDNF at excitatory synapses have been well
      characterized, the mechanisms of action of BDNF at inhibitory synapses are not
      well understood. Previously we have found that BDNF suppresses presynaptic GABA
      release in layer 2/3 of the neocortex via postsynaptic tropomyosin-related kinase
      receptor B (trkB) receptor-induced release of endocannabinoids. To examine the
      intracellular signaling pathways that underlie this effect, we used
      pharmacological approaches and whole cell patch-clamp techniques in layer 2/3
      pyramidal neurons of somatosensory cortex in brain slices from juvenile Swiss CD1
      mice. Our results indicated that phospholipase Cgamma (PLCgamma) is involved in
      the CB1 receptor-mediated synaptic effect of BDNF, because the BDNF effect was
      blocked in the presence of the broad-spectrum PLC inhibitors U-73122 and
      edelfosine, whereas the inactive analog U-73343 did not alter the suppressive
      effect of BDNF at inhibitory synapses. Endocannabinoid release can also be
      triggered by metabotropic glutamate receptor (mGluR)-mediated activation of
      PLCbeta, and BDNF has been shown to enhance spontaneous glutamate release. An
      mGluR antagonist, E4CPG, however, did not block the BDNF effect. In addition, the
      effect of BDNF was independent of other signaling pathways downstream of trkB
      receptor activation, namely, mitogen-activated protein kinase and
      phosphoinositide 3-kinase pathways, as well as protein kinase C signaling. 

PMID- 24335214
TI  - Coexpression of auxiliary Kvbeta2 subunits with Kv1.1 channels is required for
      developmental acquisition of unique firing properties of zebrafish Mauthner
      cells.
AB  - Each neuron possesses a unique firing property, which is largely attributed to
      heterogeneity in the composition of voltage-gated ion channel complexes.
      Zebrafish Mauthner (M) cells, which are bilaterally paired giant reticulospinal
      neurons (RSNs) in the hindbrain and induce rapid escape behavior, generate only a
      single spike at the onset of depolarization. This single spiking is in contrast
      with the repetitive firing of the M cell's morphologically homologous RSNs,
      MiD2cm and MiD3cm, which are also involved in escapes. However, how the unique
      firing property of M cells is established and the underlying molecular mechanisms
      remain unclear. In the present study, we first demonstrated that the single
      spiking property of M cells was acquired at 4 days postfertilization (dpf),
      accompanied by an increase in dendrotoxin I (DTX)-sensitive low-threshold K(+)
      currents, prior to which the M cell repetitively fires as its homologs. Second,
      in situ hybridization showed that among DTX-sensitive Kv1 channel alpha-subunits,
      zKv1.1a was unexpectedly expressed even in the homologs and the bursting M cells
      at 2 dpf. In contrast, zKvbeta2b, an auxiliary beta-subunit of Kv1 channels, was
      expressed only in the single-spiking M cells. Third, zKv1.1a expressed in Xenopus
      oocytes functioned as a low-threshold K(+) channel, and its currents were
      enhanced by coexpression of zKvbeta2b subunits. Finally, knockdown of zKvbeta2b
      expression in zebrafish larvae resulted in repetitive firing of M cells at 4 dpf.
      Taken together, these results suggest that associative expression of Kvbeta2
      subunits with Kv1.1 channels is crucial for developmental acquisition of the
      unique firing properties of the M cells among homologous neurons.

PMID- 24335217
TI  - Low-frequency stimulation evokes serotonin release in the nucleus accumbens and
      induces long-term depression via production of endocannabinoid.
AB  - The nucleus accumbens (NAc), a major component of the mesolimbic system, is
      involved in the mediation of reinforcing and addictive properties of many
      dependence-producing drugs. Glutamatergic synapses within the NAc can express
      plasticity, including a form of endocannabinoid (eCB)-long-term depression (LTD).
      Recent evidences demonstrate cross talk between eCB signaling pathways and those
      of other receptor systems, including serotonin (5-HT); the extensive
      colocalization of CB1 and 5-HT receptors within the NAc suggests the potential
      for interplay between them. In the present study, we found that 20-min low
      frequency (4 Hz) stimulation (LFS-4Hz) of glutamatergic afferences in rat brain
      slices induces a novel form of eCB-LTD in the NAc core, which requires 5-HT2 and
      CB1 receptor activation and L-type voltage-gated Ca(2+) channel opening.
      Moreover, we found that exogenous 5-HT application (5 MUM, 20 min) induces an
      analogous LTD (5-HT-LTD) at the same synapses, requiring the activation of the
      same receptors and the opening of the same Ca(2+) channels; LFS-4Hz-LTD and 5-HT
      LTD were mutually occlusive. Present results suggest that LFS-4Hz induces the
      release of 5-HT, which acts at 5-HT2 postsynaptic receptors, increasing Ca(2+)
      influx through L-type voltage-gated channels and 2-arachidonoylglycerol
      production and release; the eCB travels retrogradely and binds to presynaptic CB1
      receptors, causing a long-lasting decrease of glutamate release, resulting in
      LTD. These observations might be helpful to understand the neurophysiological
      mechanisms underlying drug addiction, major depression, and other psychiatric
      disorders characterized by dysfunction of 5-HT neurotransmission in the NAc. 

PMID- 24335216
TI  - Primary auditory cortical responses to electrical stimulation of the thalamus.
AB  - Cochlear implant electrical stimulation of the auditory system to rehabilitate
      deafness has been remarkably successful. Its deployment requires both an intact
      auditory nerve and a suitably patent cochlear lumen. When disease renders
      prerequisite conditions impassable, such as in neurofibromatosis type II and
      cochlear obliterans, alternative treatment targets are considered. Electrical
      stimulation of the cochlear nucleus and midbrain in humans has delivered
      encouraging clinical outcomes, buttressing the promise of central auditory
      prostheses to mitigate deafness in those who are not candidates for cochlear
      implantation. In this study we explored another possible implant target: the
      auditory thalamus. In anesthetized cats, we first presented pure tones to
      determine frequency preferences of thalamic and cortical sites. We then
      electrically stimulated tonotopically organized thalamic sites while recording
      from primary auditory cortical sites using a multichannel recording probe.
      Cathode-leading biphasic thalamic stimulation thresholds that evoked cortical
      responses were much lower than published accounts of cochlear and midbrain
      stimulation. Cortical activation dynamic ranges were similar to those reported
      for cochlear stimulation, but they were narrower than those found through
      midbrain stimulation. Our results imply that thalamic stimulation can activate
      auditory cortex at low electrical current levels and suggest an auditory thalamic
      implant may be a viable central auditory prosthesis. 

PMID- 24335218
TI  - Probing the mechanisms underlying the mitigation of cognitive aging with anodal
      transcranial direct current stimulation.
AB  - Meinzer et al. (J Neurosci 33: 12470-12478, 2013) have recently reported that
      anodal transcranial direct current stimulation (atDCS) mitigates age-related
      cognitive changes. Simultaneous measurement of BOLD signal during atDCS also
      showed "youth-like" processing in an elderly population. Although the effects are
      very promising, the underlying mechanisms of atDCS are still not clear. In this
      article, we provide a critical review of the results, emphasizing the article's
      significance and providing additional insight that will help elucidate the
      results and atDCS mechanisms. 

PMID- 24335215
TI  - Low-frequency stimulation induces long-term depression and slow onset long-term
      potentiation at perforant path-dentate gyrus synapses in vivo.
AB  - The expression of homosynaptic long-term depression (LTD) is thought to mediate a
      crucial role in sustaining memory function. Our in vivo investigations of LTD
      expression at lateral (LPP) and medial perforant path (MPP) synapses in the
      dentate gyrus (DG) corroborate prior demonstrations that PP-DG LTD is difficult
      to induce in intact animals. In freely moving animals, LTD expression occurred
      inconsistently among LPP-DG and MPP-DG responses. Interestingly, following acute
      electrode implantation in anesthetized rats, low-frequency stimulation (LFS; 900
      pulses, 1 Hz) promotes slow-onset LTP at both MPP-DG and LPP-DG synapses that
      utilize distinct induction mechanisms. Systemic administration of the N-methyl-d
      aspartate (NMDA) receptor antagonist (+/-)-cyclopiperidine-6-piperiperenzine
      (CPP; 10 mg/kg) 90 min before LFS selectively blocked MPP-DG but not LPP-DG slow
      onset LTP, suggesting MPP-DG synapses express a NMDA receptor-dependent slow
      onset LTP whereas LPP-DG slow onset LTP induction is NMDA receptor independent.
      In experiments where paired-pulse LFS (900 paired pulses, 200-ms paired-pulse
      interval) was used to induce LTD, paired-pulse LFS of the LPP resulted in rapid
      onset LTP of DG responses, whereas paired-pulse LFS of the MPP induced slow onset
      LTP of DG responses. Although LTD observations were very rare following acute
      electrode implantation in anesthetized rats, LPP-DG LTD was demonstrated in some
      anesthetized rats with previously implanted electrodes. Together, our data
      indicate in vivo PP-DG LTD expression is an inconsistent phenomenon that is
      primarily observed in recovered animals, suggesting perturbation of the dentate
      through surgery-related tissue trauma influences both LTD incidence and LTP
      induction at PP-DG synapses in vivo.

PMID- 24335219
TI  - Reorganization of hippocampal functional connectivity with transition to chronic
      back pain.
AB  - The hippocampus has been shown to undergo significant changes in rodent models of
      neuropathic pain; however, the role of the hippocampus in human chronic pain and
      its contribution to pain chronification have remained unexplored. Here we examine
      hippocampal processing during a simple visual attention task. We used functional
      MRI to identify intrinsic and extrinsic hippocampal functional connectivity
      (synchronous neural activity), comparing subacute back pain (SBP, back pain 1-4
      mo) and chronic back pain (CBP, back pain >10 yr) patients to control (CON)
      subjects. Both groups showed more extensive hippocampal connectivity than CON
      subjects. We then examined the evolution of hippocampal connectivity
      longitudinally in SBP patients who recovered (SBPr, back pain decreased >20% in 1
      yr) and those with persistent pain (SBPp). We found that SBPp and SBPr subjects
      have distinct changes in hippocampal-cortical connectivity over 1 yr;
      specifically, SBPp subjects showed large decreases in hippocampal connectivity
      with medial prefrontal cortex (HG-mPFC). Furthermore, in SBP patients the
      strength of HG-mPFC reflected variations in back pain over the year. These
      relationships were replicated when examined in a different task performed by SBP
      patients (rating fluctuations of back pain), indicating that functional
      connectivity of the hippocampus changes robustly in subacute pain and the nature
      of these changes depends on whether or not patients recover from SBP. The
      observed reorganization of processing within the hippocampus and between the
      hippocampus and the cortex seems to contribute to the transition from subacute to
      chronic pain and may also underlie learning and emotional abnormalities
      associated with chronic pain. 

PMID- 24335221
TI  - People are better at maximizing expected gain in a manual aiming task with
      rapidly changing probabilities than with rapidly changing payoffs.
AB  - Previous research has shown that humans can select movements that achieve their
      goals, while avoiding negative outcomes, by selecting an "optimal movement
      endpoint." This optimal endpoint is modeled based on the participants' endpoint
      variability and the payoffs associated with the target and penalty regions within
      the environment. Although the values associated with our goals vary on a moment
      to-moment basis in our daily interactions, the adaptation of endpoint selection
      to changing payoffs in laboratory-based tasks has been examined by varying
      contexts between blocks of trials. The present study was designed to determine
      whether participants adjust endpoints and aim to optimal endpoints and whether
      performance differs when probability or payoff parameters change from trial to
      trial. Participants aimed to a target circle that was partially overlapped by a
      penalty circle. They received 100 points for hitting the target and lost points
      for hitting the penalty area. The magnitude of the penalty value or the distance
      between the centers of the circles (related to the probability of target and
      penalty contact) was changed randomly from trial to trial in separate blocks.
      Results revealed that participants shifted their endpoint and generally aimed
      optimally when the distance between the circles was varied but did not optimally
      shift their endpoints when the penalty value was varied. The results suggest that
      participants rapidly adapted endpoints when the probabilities associated with the
      task change, because the spatial parameters are an intrinsic property of the
      visual stimuli that are tightly linked with the motor system, whereas consistent
      feedback may be necessary to adjust to value parameters effectively.

PMID- 24335220
TI  - A novel optic flow pattern speeds split-belt locomotor adaptation.
AB  - Visual input provides vital information for helping us modify our walking
      pattern. For example, artificial optic flow can drive changes in step length
      during locomotion and may also be useful for augmenting locomotor training for
      individuals with gait asymmetries. Here we asked whether optic flow could modify
      the acquisition of a symmetric walking pattern during split-belt treadmill
      adaptation. Participants walked on a split-belt treadmill while watching a
      virtual scene that produced artificial optic flow. For the Stance Congruent
      group, the scene moved at the slow belt speed at foot strike on the slow belt and
      then moved at the fast belt speed at foot strike on the fast belt. This
      approximates what participants would see if they moved over ground with the same
      walking pattern. For the Stance Incongruent group, the scene moved fast during
      slow stance and vice versa. In this case, flow speed does not match what the foot
      is experiencing, but predicts the belt speed for the next foot strike. Results
      showed that the Stance Incongruent group learned more quickly than the Stance
      Congruent group even though each group learned the same amount during adaptation.
      The increase in learning rate was primarily driven by changes in spatial control
      of each limb, rather than temporal control. Interestingly, when this alternating
      optic flow pattern was presented alone, no adaptation occurred. Our results
      demonstrate that an unnatural pattern of optic flow, one that predicts the belt
      speed on the next foot strike, can be used to enhance learning rate during split
      belt locomotor adaptation. 

PMID- 24335222
TI  - Discharge is a critical time to influence 10-year use of secondary prevention
      therapies for stroke.
AB  - BACKGROUND AND PURPOSE: When optimally managed, patients with stroke are less
      likely to have further vascular events. We aimed to identify factors associated
      with optimal use of secondary prevention therapies in long-term survivors of
      stroke. METHODS: We carefully documented discharge medications at baseline and
      self-reported use of medications at annual follow-up in the Northeast Melbourne
      Stroke Incidence Study (NEMESIS). We defined optimal medication use when patients
      reported taking (1) antihypertensive agents and (2) statin and antithrombotic
      agents (ischemic stroke only). Logistic regression was used to assess factors
      associated with optimal medication use between 2 and 10 years after stroke.
      RESULTS: We recruited 1241 patients with stroke. Optimal prescription at
      discharge from hospital was the most important factor associated with optimal
      medication use at each time point: odds ratio (OR), 32.2 (95% confidence interval
      [CI], 13.6-76.1) at 2 years; OR, 7.86 (95% CI, 4.48-13.8) at 5 years (425 of 505
      survivors); OR, 6.04 (95% CI, 3.18-11.5) at 7 years (326 of 390 survivors); and
      OR, 2.62 (95% CI, 1.19-5.77) at 10 years (256 of 293 survivors). Associations
      were similar in men and women. The association between optimal prescription at
      discharge and optimal medication use at each time point was greater in those who
      were not disadvantaged, particularly women. CONCLUSIONS: Prescription of
      medications at hospital discharge was the strongest predictor of ongoing
      medication use in survivors of stroke, even at 10 years after stroke. Ensuring
      that patients with stroke are discharged on optimal medications is likely to
      improve their long-term management, but further strategies might be required
      among those who are disadvantaged.

PMID- 24335223
TI  - ABCD3 and ABCD3-I scores are superior to ABCD2 score in the prediction of short-
      and long-term risks of stroke after transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Several risk scores have been developed to predict the
      stroke risk after transient ischemic attack (TIA). However, the validation of
      these scores in different cohorts is still limited. The objective of this study
      was to elucidate whether these scores were able to predict short-term and long
      term risks of stroke in patients with TIA. METHODS: From the Fukuoka Stroke
      Registry, 693 patients with TIA were followed up for 3 years. Multivariable
      adjusted Cox proportional hazards model was used to assess the hazard ratio of
      risk factors for stroke. The discriminatory ability of each risk score for
      incident stroke was estimated by using C-statistics and continuous net
      reclassification improvement. RESULTS: The multivariable-adjusted Cox
      proportional hazards model revealed that dual TIA and carotid stenosis were both
      significant predictors for stroke after TIA, whereas abnormal diffusion-weighted
      image was not. ABCD3 (C-statistics 0.61) and ABCD3-I (C-statistics 0.66) scores
      improved the short-term predictive ability for stroke (at 7 days) compared with
      the ABCD2 score (C-statistics 0.54). Addition of intracranial arterial stenosis
      (at 3 years, continuous net reclassification improvement 30.5%; P<0.01) and
      exclusion of abnormal diffusion-weighted imaging (at 3 years, continuous net
      reclassification improvement 24.0%; P<0.05) further improved the predictive
      ability for stroke risk until 3 years after TIA. CONCLUSIONS: The present study
      demonstrates that ABCD3 and ABCD3-I scores are superior to the ABCD2 score for
      the prediction of subsequent stroke in patients with TIA. Addition of
      neuroimaging in the ABCD3 score may enable prediction of long-term stroke risk
      after TIA.

PMID- 24335225
TI  - Organizational update: World Health Organization.

PMID- 24335224
TI  - Robotic measurement of arm movements after stroke establishes biomarkers of motor
      recovery.
AB  - BACKGROUND AND PURPOSE: Because robotic devices record the kinematics and
      kinetics of human movements with high resolution, we hypothesized that robotic
      measures collected longitudinally in patients after stroke would bear a
      significant relationship to standard clinical outcome measures and, therefore,
      might provide superior biomarkers. METHODS: In patients with moderate-to-severe
      acute ischemic stroke, we used clinical scales and robotic devices to measure arm
      movement 7, 14, 21, 30, and 90 days after the event at 2 clinical sites. The
      robots are interactive devices that measure speed, position, and force so that
      calculated kinematic and kinetic parameters could be compared with clinical
      assessments. RESULTS: Among 208 patients, robotic measures predicted well the
      clinical measures (cross-validated R(2) of modified Rankin scale=0.60; National
      Institutes of Health Stroke Scale=0.63; Fugl-Meyer=0.73; Motor Power=0.75). When
      suitably scaled and combined by an artificial neural network, the robotic
      measures demonstrated greater sensitivity in measuring the recovery of patients
      from day 7 to day 90 (increased standardized effect=1.47). CONCLUSIONS: These
      results demonstrate that robotic measures of motor performance will more than
      adequately capture outcome, and the altered effect size will reduce the required
      sample size. Reducing sample size will likely improve study efficiency.

PMID- 24335227
TI  - Alberta Stroke Program early computed tomography score to select patients for
      endovascular treatment: Interventional Management of Stroke (IMS)-III Trial.
AB  - BACKGROUND AND PURPOSE: The Interventional Management of Stroke (IMS)-III trial
      randomized patients with acute ischemic stroke to intravenous tissue-type
      plasminogen activator (tPA) plus endovascular therapy versus intravenous tPA
      therapy alone within 3 hours from symptom onset. A predefined secondary
      hypothesis was that subjects with significant early ischemic change on the
      baseline scan would not respond to endovascular therapy. METHODS: The primary
      outcome was 90-day modified Rankin Scale score 0 to 2. The baseline and follow-up
      computed tomographic (CT) scan images were reviewed centrally and blinded to any
      clinical information. We assessed whether the baseline Alberta Stroke Program
      Early CT Score (ASPECTS) predicted outcome and interacted with study treatment.
      We analyzed subgroups defined by time from onset to intravenous tPA initiation
      and baseline occlusion status at a prespecified alpha=0.01. RESULTS: Baseline
      demographic and clinical characteristics of 656 randomized patients were similar
      between subjects with a baseline ASPECTS 8 to 10 (58% of the study sample) versus
      0 to 7. Subjects with ASPECTS 8 to 10 were almost twice as likely (relative risk,
      1.8; 99% confidence interval, 1.4-2.4) to achieve a favorable outcome. There was
      insufficient evidence of a treatment-by-ASPECTS interaction. In those treated
      with onset to intravenous tPA <120 minutes, in CT angiography-proven internal
      carotid artery or middle cerebral artery occlusion, and in both, results were
      similar. The probability of achieving recanalization (arterial occlusion lesion,
      2-3) of the primary arterial occlusive lesion (relative risk, 1.3; 99% confidence
      interval, 1.0-1.8) or achieving thrombolysis in cerebral ischemia score 2b/3
      reperfusion (relative risk 2.0; 99% confidence interval, 1.2-3.2) was higher
      among subjects with higher ASPECTS. CONCLUSIONS: ASPECTS is a strong predictor of
      outcome and a predictor of reperfusion. ASPECTS did not identify a subpopulation
      of subjects that particularly benefitted from endovascular therapy immediately
      after routine intravenous tPA. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

PMID- 24335228
TI  - Fluorescent molecular peroxidation products: a prognostic biomarker of early
      neurologic deterioration after thrombolysis.
AB  - BACKGROUND AND PURPOSE: Fluorescent molecular peroxidation products (FMPPs) are
      considered potential markers of molecular oxidative damage and may provoke
      increased permeability and disruption of the blood-brain barrier. This study
      aimed to determine the value of FMPPs as a biomarker to predict neurological
      worsening related to early hemorrhagic transformation. METHODS: Baseline FMPP
      levels were measured in 186 consecutive acute ischemic stroke patients before
      tissue plasminogen activator treatment was administered. A serial FMPP profile
      (baseline before tissue plasminogen activator treatment, and 1, 2, 12, and 24
      hours from treatment) was determined in a subset of 100 patients. Computed
      tomographic scans were performed at admission and repeated at 24 to 48 hours or
      after neurological worsening occurred. Symptomatic intracranial hemorrhage was
      defined as blood at any site in the brain associated with neurological
      deterioration. RESULTS: Patients who worsened had higher median FMPP levels
      compared with those who did not (59.68 [48.63-85.73] versus 44.87 [36.37-58.90]
      Uf/mL; P=0.035) at baseline. After logistic regression multivariate analysis,
      FMPP >48.2 Uf/mL together with age, hypertension, and systolic blood pressure
      remained baseline predictors of worsening at 48 hours. Moreover, baseline FMPP
      determination helped to distinguish between patients who worsened and those who
      did not (Integrated Discrimination Improvement index, 5.7%; P=0.0004). Finally,
      within patients who had worsened at 48 hours, those with symptomatic intracranial
      hemorrhage had higher FMPP levels (P=0.038). CONCLUSIONS: FMPPs might be a
      valuable biomarker of poor early neurological outcome and be related to the
      appearance of symptomatic intracranial hemorrhage in tissue plasminogen activator
      treated patients, one of the most feared neurological complications after
      thrombolytic treatment of acute ischemic stroke.

PMID- 24335229
TI  - Concomitant infection of the tricuspid valve and right ventricle free wall after
      chest tube insertion in a young patient without predisposing diseases.
AB  - Infective endocarditis (IE) is one of the most dreaded complications of
      healthcare-associated bloodstream infection. It is an important and potentially
      lethal complication of medical care and there is incidence evidence of it in this
      population. We describe a case of concomitant infection of the tricuspid valve
      and right ventricle free wall after chest tube insertion for spontaneous
      pneumothorax in a young patient without predisposing diseases. 

PMID- 24335230
TI  - Synchronized integrin engagement and chemokine activation is crucial in
      neutrophil extracellular trap-mediated sterile inflammation.
AB  - There is emerging evidence that neutrophil extracellular traps (NETs) play
      important roles in inflammatory processes. Here we report that neutrophils have
      to be simultaneously activated by integrin-mediated outside-in- and G-protein
      coupled receptor (GPCR) signaling to induce NET formation in acute lung injury
      (ALI), which is associated with a high mortality rate in critically ill patients.
      NETs consist of decondensed chromatin decorated with granular and cytosolic
      proteins and they can trap extracellular pathogens. The prerequisite for NET
      formation is the activation of neutrophils and the release of their DNA. In a
      neutrophil- and platelet-dependent mouse model of ventilator-induced lung injury
      (VILI), NETs were found in the lung microvasculature, and circulating NET
      components increased in the plasma. In this model, blocking integrin-mediated
      outside-in or either GPCR-signaling or heteromerization of platelet chemokines
      decreased NET formation and lung injury. Targeting NET components by DNAse1
      application or neutrophil elastase-deficient mice protected mice from ALI,
      whereas DNase1(-/-)/Trap1(m/m) mice had an aggravated ALI, suggesting that NETs
      directly influence the severity of ALI. These data suggest that NETs form in the
      lungs during VILI, contribute to the disease process, and thus may be a promising
      new direction for the treatment of ALI. 

PMID- 24335231
TI  - Inhibitors of apoptosis proteins (IAPs) are required for effective T-cell
      expansion/survival during antiviral immunity in mice.
AB  - Inhibitors of apoptosis proteins (IAPs) were originally described as regulating
      apoptosis by direct binding to caspases. More recently, IAPs have been identified
      as important modulators of canonical and noncanonical nuclear factor kappaB
      signaling via their ubiquitin-E3 ligase activity. IAPs are therefore, not only
      gatekeepers of cell death, but are probably also involved in the regulation of
      inflammation, as well as innate and adaptive immunity. In this study, we analyzed
      the role of IAPs in T-cell immunity during lymphocytic choriomeningitis virus
      (LCMV) infection by pharmacological targeting with an IAP antagonist/second
      mitochondria-derived activator of caspase-mimetic. Expansion of virus-specific
      CD8 T cells was drastically reduced in LCMV-infected mice exposed to IAP
      antagonists. Accordingly, virus control was substantially impaired, indicated by
      high virus titres in the spleen and the spread of LCMV to peripheral organs. The
      profound negative effect of IAP antagonists on T-cell immunity was partially
      linked to tumor necrosis factor-mediated cell death of activated T cells and
      required inhibition of X-linked inhibitor of apoptosis, as well as cellular IAP
      1. Thus, IAPs play an important role in T-cell expansion and survival in the
      context of a highly inflammatory environment such as a virus infection,
      indicating that IAP antagonists may interfere with immune responses. 

PMID- 24335232
TI  - Exosomes from red blood cell units bind to monocytes and induce proinflammatory
      cytokines, boosting T-cell responses in vitro.
AB  - Extracellular vesicles (EVs) are small, double membrane vesicles derived from
      leukocytes, platelets, and cells of other tissues under physiological or
      pathological conditions. Generation of EVs in stored blood is thought to be
      associated with adverse effects and potentially immunosuppression in blood
      transfusion recipients. We measured the quantity and cells of origin for EVs
      isolated from stored red blood cell (RBC) units and tested whether they had any
      effects on T-cell-mediated immune responses. Mixing peripheral blood mononuclear
      cells (PBMCs) with EVs resulted in secretion of proinflammatory cytokines and
      chemokines and increased survival of unstimulated PBMCs. EVs augmented mitogen
      induced CD4(+) and CD8(+) T-cell proliferation in an antigen-presenting cell
      (APC)-dependent manner. We demonstrated that EVs interacted primarily with
      monocytes and induced proinflammatory cytokine secretion. We also showed that the
      exosome fraction of EVs and not larger microvesicles was responsible for
      induction of TNF-alpha production by monocytes. Furthermore, blockade of CD40 or
      CD40L accessory molecules largely neutralized the EV augmentation of T-cell
      responses, implying a role for cell-cell interaction between T cells and EV
      activated monocytes. Contrary to our hypothesis, the data demonstrate that EVs
      isolated from RBC units increase the potency of APCs and boost mitogen-driven T
      cell proliferative responses. 

PMID- 24335233
TI  - Platelet transfusions for critically ill patients with thrombocytopenia.

PMID- 24335235
TI  - Multiple nonsteroidal anti-inflammatory drug-induced cutaneous disease: what
      differentiates patients with and without underlying chronic spontaneous
      urticaria?
AB  - BACKGROUND: Multiple nonsteroidal anti-inflammatory drug (NSAID) cutaneous
      reactors may be otherwise normal or have underlying chronic spontaneous urticaria
      (CSU). This study compared these two phenotypes of NSAID-hypersensitive subjects.
      METHODS: A total of 97 multiple NSAID reactors underwent oral challenges with
      paracetamol, etoricoxib and tramadol. Atopic status was investigated in all
      patients, and autoreactivity was ascertained in some cases as well. Otherwise
      normal multiple NSAID reactors were reevaluated after 1-5 years in order to
      detect their proneness to CSU. RESULTS: At the first visit, 41 patients had CSU
      and 56 had multiple NSAID intolerance without any underlying cutaneous disease.
      Altogether, 22, 10 and 6% of patients did not tolerate paracetamol, etoricoxib
      and tramadol, respectively, on oral challenge. Intolerance to these alternative
      drugs showed a strong association (p < 0.01 with all combinations). The two
      subgroups of patients did not show any difference in terms of mean age, gender
      distribution, prevalence of atopic diseases, prevalence of single offending
      NSAIDs and prevalence of intolerance to paracetamol, etoricoxib or tramadol on
      oral challenge. In all, 20% of multiple NSAID reactors without CSU at
      presentation developed CSU between 6 months and 5 years after the initial
      clinical evaluation. CONCLUSIONS: Multiple NSAID cutaneous reactors with or
      without CSU seem identical from a clinical point of view, and some of the latter
      group show a propensity to acquire the former phenotype over time. A subset of
      patients apparently identical to the general population of multiple NSAID
      reactors also react to drugs exerting little or no cyclooxygenase-1 enzyme
      inhibition and might represent a distinct phenotype of NSAID-hypersensitive
      patients possibly characterized by a different underlying pathogenesis.

PMID- 24335234
TI  - SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in
      response to DNA damage.
AB  - SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase and a nuclease that
      restricts HIV-1 in noncycling cells. Germ-line mutations in SAMHD1 have been
      described in patients with Aicardi-Goutieres syndrome (AGS), a congenital
      autoimmune disease. In a previous longitudinal whole genome sequencing study of
      chronic lymphocytic leukemia (CLL), we revealed a SAMHD1 mutation as a potential
      founding event. Here, we describe an AGS patient carrying a pathogenic germ-line
      SAMHD1 mutation who developed CLL at 24 years of age. Using clinical trial
      samples, we show that acquired SAMHD1 mutations are associated with high variant
      allele frequency and reduced SAMHD1 expression and occur in 11% of
      relapsed/refractory CLL patients. We provide evidence that SAMHD1 regulates cell
      proliferation and survival and engages in specific protein interactions in
      response to DNA damage. We propose that SAMHD1 may have a function in DNA repair
      and that the presence of SAMHD1 mutations in CLL promotes leukemia development. 

PMID- 24335236
TI  - Introductory commentary: a precis on the well-being of young Americans.

PMID- 24335237
TI  - Strategies to improve adolescent health: lessons learned.

PMID- 24335238
TI  - Digital video technology and production 101: lights, camera, action.
AB  - Videos are powerful tools for enhancing the reach and effectiveness of health
      promotion programs. They can be used for program promotion and recruitment, for
      training program implementation staff/volunteers, and as elements of an
      intervention. Although certain brief videos may be produced without technical
      assistance, others often require collaboration and contracting with professional
      videographers. To get practitioners started and to facilitate interactions with
      professional videographers, this Tool includes a guide to the jargon of video
      production and suggestions for how to integrate videos into health education and
      promotion work. For each type of video, production principles and issues to
      consider when working with a professional videographer are provided. The Tool
      also includes links to examples in each category of video applications to health
      promotion. 

PMID- 24335240
TI  - Thorax: the prostate years.

PMID- 24335241
TI  - Response To Preiksaitis and Limaye.

PMID- 24335244
TI  - Saphenous vein graft disease and neutrophil-to-lymphocyte ratio.

PMID- 24335245
TI  - Association of neutrophil-lymphocyte ratio with the presence and severity of
      rheumatic mitral valve stenosis.
AB  - The aim of the study is to investigate the association between the severity of
      rheumatic mitral valvular disease (RMVD) and the neutrophil-lymphocyte ratio
      (NLR). A total of 227 patients were enrolled in the study and divided into 3
      groups. Patients in group 1 had rheumatic mitral stenosis (RMS), those in group 2
      had RMVD without stenosis, and those in group 3 served as the control group.
      Group 1 was further divided into 2 groups, severe mitral stenosis (MS) and mild
      to moderate MS. The NLR was significantly higher in patients with severe MS when
      compared to those with mild to moderate MS (P = .002) while lymphocyte count was
      lower (P = .034). Using a cutoff level of 2.56, the NLR predicted severe RMS with
      a sensitivity of 75% and specificity of 74%. In conclusion, as an inexpensive,
      simple, and accessible marker of inflammation, the NLR may be useful in
      predicting the presence and severity of MS in patients with RMVD.

PMID- 24335246
TI  - Risk Factors and Treatment Strategies in Patients With Retinal Vascular
      Occlusions.
AB  - Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) cause significant
      visual impairment. The role of thrombophilia and cardiovascular testing is
      uncertain, and optimal treatment strategies have not been determined. We reviewed
      medical records of 39 patients with RVO and RAO (23 women and 16 men).
      Thrombophilia and cardiovascular evaluations were performed and outcomes were
      reviewed. In all, 24 (61.5%) patients had at least 1 thrombophilia. Elevated
      factor VIII levels were found in RVO (n = 5) but not in RAO. There are no other
      significant differences in thrombophilias in RVO compared to those in RAO. Most
      patients had hypertension(41.2% RAO and 55% RVO) and hyperlipidemia (35.5% RAO
      and 81.8% RVO). In all, 4 women were using oral contraceptives, 2 were pregnant
      or postpartum. Follow-up data was available for 28 patients (13 RAO, 15 RVO).
      Nineteen were treated with aspirin, four with warfarin, and one with low
      molecular weight heparin. Eight patients reported improvement in vision at time
      of follow-up (5 RAO, 3 RVO). Multiple risk factors are associated with RVO and
      RAO, and a complete assessment should include thrombophilia and cardiovascular
      studies.

PMID- 24335247
TI  - Prevalence of the Factor V E666D Mutation and Its Correlation With Activated
      Protein C Resistance in the Chinese Population.
AB  - BACKGROUND: Factor V (FV) Leiden mutation-related activated protein C resistance
      (APCR) is one of the common inherited risk factors for venous thromboembolism
      (VTE) in caucasian population. Although APCR could be identified in some of the
      Chinese healthy people and patients with VTE, it was not related to FV Leiden
      mutation. In 2008, we have identified a novel FV mutation (FV E666D) in exon 13
      in a hereditary APCR family. And we presumed that the novel mutation might be a
      genetic defect of APCR in the Chinese population. The aim of our study was to
      evaluate the prevalence of FV E666D mutation and its correlation with APCR in the
      Chinese population in a larger series. METHODS: From June 2009 to January 2011,
      163 consecutive patients who underwent thrombophilia tests in our hospital were
      recruited. The clinical data were retrospectively reviewed. Thrombophilia tests
      included APCR, anticoagulant proteins, and antiphospholipid antibodies. Factor V
      E666D mutation was detected. RESULT: Of the 163 patients, 6 (3.7%) were
      identified as APCR positive, 2.9% for patients without thrombosis and 5.1% for
      patients with thrombosis or thrombosis history. Factor V E666D mutation was not
      detectable in all the 163 patients including 6 APCR-positive patients.
      CONCLUSIONS: The prevalence of APCR either in the nonthrombotic patients or in
      the patients with thrombosis was lower than that reported in other Chinese
      studies. Our study couldn't provide illustration whether FV E666D mutation is
      correlated with APCR in the Chinese population.

PMID- 24335248
TI  - Lower incidence of M2/ANXA5 carriage in recurrent pregnancy loss patients with
      elevated lipoprotein(a) levels.
AB  - This study compared the incidence of M2/ANXA5 haplotype carriage, a documented
      repeated miscarriage risk factor, in patient groups with normal and elevated
      lipoprotein(a) (Lp(a)) levels. A total of 138 women with >=2 consecutive,
      idiopathic recurrent miscarriages, categorized in patients with elevated (>=30
      mg/dL, n = 44) and normal Lp(a) level (<30 mg/dL, n = 94) were recruited at the
      recurrent pregnancy loss (RPL) clinic of Munich Grobetahadern University
      Hospital. A total of 500 fertile women served as controls. All patients were
      genotyped for ANXA5 promoter haplotypes, genetic frequencies were compared, and
      odds ratios (ORs) and relative risks of M2 carriers were calculated. Women with
      M2 haplotype had an almost 2 times higher relative risk of RPL (OR 2.6, 95%
      confidence interval 1.5-4.6, P = .001) than fertile controls. Furthermore, risk
      rises to 2.47 in patients having normal Lp(a) levels (OR 3.2, 95% confidence
      interval 1.7-5.9, P = .001), whereas women with high Lp(a) levels exhibit notably
      lower apparent RPL risk of 1.39 (OR 1.4, 95% confidence interval 0.5-4.1, P =
      .659). 

PMID- 24335249
TI  - Pharmacokinetics of recombinant human antithrombin in delivery and surgery
      patients with hereditary antithrombin deficiency.
AB  - Population pharmacokinetic (PK) analyses were conducted to refine dosing
      recommendations for recombinant human anti-thrombin therapy in surgery and
      delivery patients with hereditary antithrombin deficiency (HD). Single-dose PK
      data from patients with HD and nonlinear mixed-effects modeling were used to
      devise a dosing regimen to target antithrombin (AT) activity levels between 80%
      and 120% of normal. External validation with data from a phase 3 trial confirmed
      the correctness of a covariate-free model for surgery patients, but dosing
      adjustment was necessary for delivery patients. After different covariates were
      tested, the model was updated to incorporate the influential covariate, delivery.
      Simulations were used to develop a therapeutic drug-monitoring scenario that
      results in steady state AT activity levels within the target range as quickly as
      practically feasible. Data from a second clinical trial provided additional
      external validation and confirmed the accuracy of the dosing model for both
      groups of patients. 

PMID- 24335250
TI  - The role of scientific publication in times of change.

PMID- 24335251
TI  - Putting the 'i' in iHealth.

PMID- 24335252
TI  - PRDM14 promotes active DNA demethylation through the ten-eleven translocation
      (TET)-mediated base excision repair pathway in embryonic stem cells.
AB  - Ten-eleven translocation (TET) proteins oxidize 5-methylcytosine (5mC) to 5
      hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine
      (5caC). 5fC and 5caC can be excised and repaired by the base excision repair
      (BER) pathway, implicating 5mC oxidation in active DNA demethylation. Genome-wide
      DNA methylation is erased in the transition from metastable states to the ground
      state of embryonic stem cells (ESCs) and in migrating primordial germ cells
      (PGCs), although some resistant regions become demethylated only in gonadal PGCs.
      Understanding the mechanisms underlying global hypomethylation in naive ESCs and
      developing PGCs will be useful for realizing cellular pluripotency and
      totipotency. In this study, we found that PRDM14, the PR domain-containing
      transcriptional regulator, accelerates the TET-BER cycle, resulting in the
      promotion of active DNA demethylation in ESCs. Induction of Prdm14 expression
      transiently elevated 5hmC, followed by the reduction of 5mC at pluripotency
      associated genes, germline-specific genes and imprinted loci, but not across the
      entire genome, which resembles the second wave of DNA demethylation observed in
      gonadal PGCs. PRDM14 physically interacts with TET1 and TET2 and enhances the
      recruitment of TET1 and TET2 at target loci. Knockdown of TET1 and TET2 impaired
      transcriptional regulation and DNA demethylation by PRDM14. The repression of the
      BER pathway by administration of pharmacological inhibitors of APE1 and PARP1 and
      the knockdown of thymine DNA glycosylase (TDG) also impaired DNA demethylation by
      PRDM14. Furthermore, DNA demethylation induced by PRDM14 takes place normally in
      the presence of aphidicolin, which is an inhibitor of G1/S progression. Together,
      our analysis provides mechanistic insight into DNA demethylation in naive
      pluripotent stem cells and developing PGCs. 

PMID- 24335253
TI  - Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate
      independently of isthmic organizing activity.
AB  - During embryonic development, the rostral neuroectoderm is regionalized into
      broad areas that are subsequently subdivided into progenitor compartments with
      specialized identity and fate. These events are controlled by signals emitted by
      organizing centers and interpreted by target progenitors, which activate
      superimposing waves of intrinsic factors restricting their identity and fate. The
      transcription factor Otx2 plays a crucial role in mesencephalic development by
      positioning the midbrain-hindbrain boundary (MHB) and its organizing activity.
      Here, we investigated whether Otx2 is cell-autonomously required to control
      identity and fate of dorsal mesencephalic progenitors. With this aim, we have
      inactivated Otx2 in the Pax7(+) dorsal mesencephalic domain, previously named m1,
      without affecting MHB integrity. We found that the Pax7(+) m1 domain can be
      further subdivided into a dorsal Zic1(+) m1a and a ventral Zic1(-) m1b sub
      domain. Loss of Otx2 in the m1a (Pax7(+) Zic1(+)) sub-domain impairs the identity
      and fate of progenitors, which undergo a full switch into a coordinated
      cerebellum differentiation program. By contrast, in the m1b sub-domain (Pax7(+)
      Zic1(-)) Otx2 is prevalently required for post-mitotic transition of
      mesencephalic GABAergic precursors. Moreover, genetic cell fate, BrdU cell
      labeling and Otx2 conditional inactivation experiments indicate that in Otx2
      mutants all ectopic cerebellar cell types, including external granule cell layer
      (EGL) precursors, originate from the m1a progenitor sub-domain and that
      reprogramming of mesencephalic precursors into EGL or cerebellar GABAergic
      progenitors depends on temporal sensitivity to Otx2 ablation. Together, these
      findings indicate that Otx2 intrinsically controls different aspects of dorsal
      mesencephalic neurogenesis. In this context, Otx2 is cell-autonomously required
      in the m1a sub-domain to suppress cerebellar fate and promote mesencephalic
      differentiation independently of the MHB organizing activity. 

PMID- 24335254
TI  - Translocating myonuclei have distinct leading and lagging edges that require
      kinesin and dynein.
AB  - Nuclei are precisely positioned within all cells, and mispositioned nuclei are a
      hallmark of many muscle diseases. Myonuclear positioning is dependent on Kinesin
      and Dynein, but interactions between these motor proteins and their mechanisms of
      action are unclear. We find that in developing Drosophila muscles, Dynein and
      Kinesin work together to move nuclei in a single direction by two separate
      mechanisms that are spatially segregated. First, the two motors work together in
      a sequential pathway that acts from the cell cortex at the muscle poles. This
      mechanism requires Kinesin-dependent localization of Dynein to cell cortex near
      the muscle pole. From this location Dynein can pull microtubule minus-ends and
      the attached myonuclei toward the muscle pole. Second, the motors exert forces
      directly on individual nuclei independently of the cortical pathway. However, the
      activities of the two motors on the nucleus are polarized relative to the
      direction of myonuclear translocation: Kinesin acts at the leading edge of the
      nucleus, whereas Dynein acts at the lagging edge of the nucleus. Consistent with
      the activities of Kinesin and Dynein being polarized on the nucleus, nuclei
      rarely change direction, and those that do, reorient to maintain the same leading
      edge. Conversely, nuclei in both Kinesin and Dynein mutant embryos change
      direction more often and do not maintain the same leading edge when changing
      directions. These data implicate Kinesin and Dynein in two distinct and
      independently regulated mechanisms of moving myonuclei, which together maximize
      the ability of myonuclei to achieve their proper localizations within the
      constraints imposed by embryonic development. 

PMID- 24335255
TI  - Src64B phosphorylates Dumbfounded and regulates slit diaphragm dynamics:
      Drosophila as a model to study nephropathies.
AB  - Drosophila nephrocytes are functionally homologous to vertebrate kidney
      podocytes. Both share the presence of slit diaphragms that function as molecular
      filters during the process of blood and haemolymph ultrafiltration. The protein
      components of the slit diaphragm are likewise conserved between flies and humans,
      but the mechanisms that regulate slit diaphragm dynamics in response to injury or
      nutritional changes are still poorly characterised. Here, we show that
      Dumbfounded/Neph1, a key diaphragm constituent, is a target of the Src kinase
      Src64B. Loss of Src64B activity leads to a reduction in the number of diaphragms,
      and this effect is in part mediated by loss of Dumbfounded/Neph1 tyrosine
      phosphorylation. The phosphorylation of Duf by Src64B, in turn, regulates Duf
      association with the actin regulator Dock. We also find that diaphragm damage
      induced by administration of the drug puromycin aminonucleoside (PAN model)
      directly associates with Src64B hyperactivation, suggesting that diaphragm
      stability is controlled by Src-dependent phosphorylation of diaphragm components.
      Our findings indicate that the balance between diaphragm damage and repair is
      controlled by Src-dependent phosphorylation of diaphragm components, and point to
      Src family kinases as novel targets for the development of pharmacological
      therapies for the treatment of kidney diseases that affect the function of the
      glomerular filtration barrier. 

PMID- 24335257
TI  - Raeppli: a whole-tissue labeling tool for live imaging of Drosophila development.
AB  - Observation of how cells divide, grow, migrate and form different parts of a
      developing organism is crucial for understanding developmental programs. Here, we
      describe a multicolor imaging tool named Raeppli (after the colorful confetti
      used at the carnival in Basel). Raeppli allows whole-tissue labeling such that
      the descendants of the majority of cells in a single organ are labeled and can be
      followed simultaneously relative to one another. We tested the use of Raeppli in
      the Drosophila melanogaster wing imaginal disc. Induction of Raeppli during
      larval stages irreversibly labels >90% of the cells with one of four spectrally
      separable, bright fluorescent proteins with low bias of selection. To understand
      the global growth characteristics of imaginal discs better, we induced Raeppli at
      various stages of development, imaged multiple fixed discs at the end of their
      larval development and estimated the size of their pouch primordium at those
      developmental stages. We also imaged the same wing disc through the larval
      cuticle at different stages of its development; the clones marked by Raeppli
      provide landmarks that can be correlated between multiple time points. Finally,
      we used Raeppli for continuous live imaging of prepupal eversion of the wing
      disc. 

PMID- 24335256
TI  - Numb family proteins are essential for cardiac morphogenesis and progenitor
      differentiation.
AB  - Numb family proteins (NFPs), including Numb and numb-like (Numbl), are cell fate
      determinants for multiple progenitor cell types. Their functions in cardiac
      progenitor differentiation and cardiac morphogenesis are unknown. To avoid early
      embryonic lethality and study NFP function in later cardiac development, Numb and
      Numbl were deleted specifically in heart to generate myocardial double-knockout
      (MDKO) mice. MDKOs were embryonic lethal and displayed a variety of defects in
      cardiac progenitor differentiation, cardiomyocyte proliferation, outflow tract
      (OFT) and atrioventricular septation, and OFT alignment. By ablating NFPs in
      different cardiac populations followed by lineage tracing, we determined that
      NFPs in the second heart field (SHF) are required for OFT and atrioventricular
      septation and OFT alignment. MDKOs displayed an SHF progenitor cell
      differentiation defect, as revealed by a variety of methods including mRNA deep
      sequencing. Numb regulated cardiac progenitor cell differentiation in an
      endocytosis-dependent manner. Studies including the use of a transgenic Notch
      reporter line showed that Notch signaling was upregulated in the MDKO.
      Suppression of Notch1 signaling in MDKOs rescued defects in p57 expression,
      proliferation and trabecular thickness. Further studies showed that Numb inhibits
      Notch1 signaling by promoting the degradation of the Notch1 intracellular domain
      in cardiomyocytes. This study reveals that NFPs regulate trabecular thickness by
      inhibiting Notch1 signaling, control cardiac morphogenesis in a Notch1
      independent manner, and regulate cardiac progenitor cell differentiation in an
      endocytosis-dependent manner. The function of NFPs in cardiac progenitor
      differentiation and cardiac morphogenesis suggests that NFPs might be potential
      therapeutic candidates for cardiac regeneration and congenital heart diseases. 

PMID- 24335258
TI  - Influence of mesenchymal stem cells on the response of endothelial cells to
      laminar flow and shear stress.
AB  - The interactions between endothelial cells (ECs) and smooth muscle cells (SMCs)
      in a complex hemodynamic environment play an important role in the control of
      blood vessel function. Since autologous SMCs are not readily available for the
      tissue engineering of a blood vessel substitute, a substitute for SMCs, such as
      human adult bone marrow-derived mesenchymal stem cells (MSCs), is needed. The
      objective of this study was to use a three-dimensional coculture model of the
      blood vessel wall, comprised of ECs and MSCs, to determine how the presence of
      MSCs affects EC function. Two vascular coculture models with an EC monolayer were
      created using type I collagen. All models were exposed to steady laminar flow
      with a shear stress of 15 dyn/cm(2) for up to 48 h. ECs in both the MSC and SMC
      coculture models expressed up-regulated EC-specific markers compared to the EC
      only control model. The most dramatic difference observed between the two
      coculture models was in the experiments assessing monocyte adhesion. Here, fewer
      monocytes bound after laminar shear compared to static conditions; however, the
      number of bound monocytes was much lower for the EC-MSC coculture model than the
      EC-SMC coculture model for both static and shear conditions. These results
      suggest the feasibility of developing a tissue-engineered blood vessel substitute
      using MSCs as a substitute for SMCs.

PMID- 24335261
TI  - The brain of the horse: weight and cephalization quotients.
AB  - The horse is a common domestic animal whose anatomy has been studied since the
      XVI century. However, a modern neuroanatomy of this species does not exist and
      most of the data utilized in textbooks and reviews derive from single specimens
      or relatively old literature. Here, we report information on the brain of Equus
      caballus obtained by sampling 131 horses, including brain weight (as a whole and
      subdivided into its constituents), encephalization quotient (EQ), and cerebellar
      quotient (CQ), and comparisons with what is known about other relevant species.
      The mean weight of the fresh brains in our experimental series was 598.63 g (SEM
      +/- 7.65), with a mean body weight of 514.12 kg (SEM +/- 15.42). The EQ was 0.78
      and the CQ was 0.841. The data we obtained indicate that the horse possesses a
      large, convoluted brain, with a weight similar to that of other hoofed species of
      like mass. However, the shape of the brain, the noteworthy folding of the
      neocortex, and the peculiar longitudinal distribution of the gyri suggest an
      evolutionary specificity at least partially separate from that of the
      Cetartiodactyla (even-toed mammals and cetaceans) with whom Perissodactyla (odd
      toed mammals) are often grouped.

PMID- 24335260
TI  - JNK signaling is needed to tolerate chromosomal instability.
AB  - Chromosomal instability (CIN), as a common feature of tumors, represents a
      potential therapeutic target if ways can be found to specifically cause apoptosis
      in unstably dividing cells. We have previously shown that if signaling through
      the JNK pathway is reduced, apoptosis is triggered in models of chromosomal
      instability induced by loss of the spindle checkpoint. Here we identify
      components upstream and downstream of JNK that are able to mediate this effect,
      and test the involvement of p53 and DNA damage in causing apoptosis when JNK
      signaling is reduced in CIN cells. We show that cell cycle progression timing has
      a strong effect on the apoptosis seen when JNK signaling is reduced in
      genetically unstable cells: a shortened G 2 phase enhances the apoptosis, while
      lengthening G 2 rescues the JNK-deficient CIN cell death phenotype. Our findings
      suggest that chromosomal instability represents a significant stress to dividing
      cells, and that without JNK signaling, cells undergo apoptosis because they lack
      a timely and effective response to DNA damage. 

PMID- 24335262
TI  - Pathological analysis of the aortic valve after long-term left ventricular assist
      device support.
AB  - OBJECTIVES: Aortic insufficiency (AI) often develops during left ventricular
      assist device (LVAD) support and is related to a poor prognosis. As LVAD
      implantation and the support duration increase, the risk of acquired aortic valve
      lesions may increase. We investigated the pathological changes in the aortic
      valve and its function after long-term LVAD support. METHODS: Thirty-five hearts
      removed at heart transplantation were investigated. Thirty-one patients were
      supported by extracorporeal pulsatile devices, and 4 were supported by
      implantable devices. We compared the histological changes in the aortic valve
      with the echocardiogram results. RESULTS: The mean duration of LVAD support was
      961 days. Before device implantation, all patients had a normal aortic valve
      opening, and only 5 had trivial AI. After LVAD support, trivial AI was observed
      in 18 patients, mild AI in 4 and mild-to-moderate AI in 2. Pathological
      examination revealed that the aortic valve had become thinner in all patients,
      ranging from 120 to 1400 um. The aortic wall had also become thinner in most
      patients, ranging from 830 to 2220 um. Left ventricular wall thickness was
      ranging from 4 to 13 mm, and aortic annular diameter was ranging from 17 to 27
      mm. Partial aortic valve fusion was seen in 17 (48.6%) recipients, and curling
      with leaflet shortening was detected in 22 (62.9%) patients. Dense collagen
      accumulation in the spongiosa layer was also present. All aortic valves of the
      patients with mild and mild-to-moderate AI showed a scarce or no opening before
      explantation. Conversely, the AI grade of patients whose aortic valve frequently
      opened remained none or trivial. There was no close correlation between these
      pathological findings and the development of AI independently. CONCLUSIONS:
      Degenerative aortic valve changes were recognized after long-term LVAD support.
      There was also an increasing prevalence of mild and mild-to-moderate AI, which
      may have been associated with continuous aortic valve closure. An optimal
      strategy to prevent AI development should be determined, and careful periodic
      echocardiographic follow-up is essential.

PMID- 24335263
TI  - Severe calcification of a Shelhigh stentless valved conduit.

PMID- 24335264
TI  - A papillary-ventricular complex repair technique for functional mitral
      regurgitation.
AB  - The objective of this study was to describe a simple and reproducible papillary
      ventricular complex technique for repairing functional mitral regurgitation. To
      avoid a recurrence of mitral regurgitation subsequent to left ventricular
      remodelling, we performed papillary muscle plication and papillary muscle and
      head approximation in combination with relocation of the papillary muscle heads
      to correct any anterior and or posterior mitral leaflet discrepancy and to
      preserve the papillary-ventricular complex. Preliminary results in 7 patients
      showed an encouraging functional improvement following surgery. Future long-term
      controlled studies in a greater number of patients are required to further assess
      this novel technique. 

PMID- 24335265
TI  - Adopting a standardized anterior approach significantly increases video-assisted
      thoracoscopic surgery lobectomy rates.
AB  - OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) lobectomy is associated
      with improved short-term outcomes compared with thoracotomy. Definition of the
      hilar structures is crucial to safe VATS lobectomy. Several VATS approaches have
      been described. We report the effect of three surgeons in our institution
      undertaking standardized anterior approach (SAA) training on the proportion of
      isolated lobectomies subsequently completed by VATS. Predictors of successful
      VATS lobectomy were analysed. METHODS: Three consultant surgeons undertook SAA
      training at two different time points. Two were performing VATS lobectomy prior
      to SAA training. Training involved a 2-day visit to an established SAA unit.
      Lobectomies performed by these surgeons between April 2011 and December 2012 (20
      months), before and after training, were recorded prospectively. Bilobectomies,
      sleeve resections, pneumonectomies and chest wall resections were excluded. VATS
      lobectomy proportions before and after training were compared. Independent
      predictors of completion by VATS rather than thoracotomy were identified by
      multivariable logistic regression. RESULTS: One hundred and sixty-three isolated
      lobectomies were performed, 97 of these by VATS (59.5%). The mean age was 68.8
      (+/- 10.5) years. Pathology was lung cancer in 137 (84.0%), other primary
      malignancy in 10 (6.1%), pulmonary metastases in 8 (4.9%) and benign in 8 (4.9%).
      The VATS lobectomy rate rose from 22.2% before SAA training to 77.3% after, P <
      0.001. The effect was significant for both existing and adopting VATS lobectomy
      surgeons, P = 0.002 to <0.001. The median hospital stay was 4 days after VATS and
      5 after thoracotomy, P < 0.001. There were 5 in-hospital deaths after thoracotomy
      and none after VATS lobectomy, unadjusted P = 0.01. In the final logistic
      regression model, SAA training was the strongest predictor of successful VATS
      lobectomy (odds ratio 15.16; 95% confidence interval 6.39, 35.96). CONCLUSIONS:
      Formal training and adoption of the SAA approach were associated with a more than
      3-fold increase in our VATS lobectomy rate. The effect was immediate and
      sustained. This may reflect easier identification of the major structures from
      the anterior view. In addition, standardization of surgical techniques and
      perioperative protocols may facilitate efficient team working. VATS lobectomy was
      associated with a shorter median hospital stay. Units seeking to increase their
      VATS lobectomy rate should consider group adoption of the SAA approach.

PMID- 24335266
TI  - Transapical transcatheter aortic valve implantation without prior balloon aortic
      valvuloplasty: feasible and safe.
AB  - OBJECTIVES: Currently, preimplant balloon aortic valvuloplasty (BAV) is
      considered a prerequisite for successful subsequent transapical transcatheter
      aortic valve implantation (TA-TAVI) using balloon-expandable devices. However,
      cerebral embolization has been shown to originate at least in part from BAV
      procedures. Omitting BAV may therefore reduce neurological events after TAVI and
      facilitate the procedure while yielding non-inferior haemodynamic and clinical
      outcomes. METHODS: From May 2011 through December 2012, a total of 50 consecutive
      patients were treated by TA-TAVI without preimplant BAV (TA-TAVI(-BAV), study
      group) using the Edwards Sapien XT device (54% male, age 78 +/- 8 years, logistic
      European System for Cardiac Operative Risk Evaluation I 21 +/- 14%). Data were
      prospectively entered into a dedicated database, retrospectively analysed and
      compared with a consecutive series of conventional TA-TAVI using the same device
      (control group, n = 50). Reporting of data followed Valve Academic Research
      Consortium definitions. RESULTS: Overall device success rate was 94% (47/50) and
      86% (43/50) in study and control groups, respectively (P = 0.32). Procedure time
      was similar in the study group compared with the control group (88 +/- 31 vs 91
      +/- 25 min, P = 0.60), while significantly less contrast was used (138 +/- 68 vs
      183 +/- 78 ml, P < 0.001). Post-procedural peak and mean transvalvular gradients
      were 16 +/- 7 and 8 +/- 3 mmHg, respectively, in the study group with similar
      values in the control group (19 +/- 9 and 9 +/- 5 mmHg, P = 0.08 and P = 0.09,
      respectively). Residual paravalvular leakage (PVL) grade 2 was present in 2 and
      8% in study and control groups, respectively (P = 0.36), with no PVL >grade 2 in
      any patient. Rates of 30-day mortality and periprocedural stroke were 4 and 10%
      (P = 0.44) and 2 and 6% (P = 0.62), respectively. CONCLUSIONS: TA-TAVI(-BAV) is
      feasible and safe and has become ur default technique for patients allocated to
      TA-TAVI with balloon-expandable devices. This approach resulted in less contrast
      agent used and facilitated the procedure without compromising valve performance.
      Possible beneficial effects of this approach on the incidence of cerebrovascular
      events, other periprocedural complications or haemodynamic valve performance need
      to be verified in larger patient numbers before general recommendations can be
      made.

PMID- 24335267
TI  - Clinical trial of video-assisted thoracoscopic segmentectomy using infrared
      thoracoscopy with indocyanine green.
AB  - OBJECTIVES: The maintenance of a good surgical view is mandatory in video
      assisted thoracoscopic surgery (VATS). For routine segmentectomy, it is necessary
      to re-inflate the lung in order to identify the intersegmental line. However,
      such re-inflation can occasionally obstruct the surgical view. Infrared
      thoracoscopy (IRT) with indocyanine green (ICG) can reveal the intersegmental
      line based on blood flow differences, without the need for lung re-inflation. The
      purpose of this study was to confirm the usefulness of IRT with ICG for VATS.
      METHODS: Between October 2008 and September 2011, 44 consecutive patients
      underwent segmentectomy at our institution. In 13 patients, VATS segmentectomy
      using IRT with ICG was employed. Informed consent was obtained from all patients.
      Computed tomography was performed to identify the dominant pulmonary artery
      supplying the target segment. The operations were performed using two ports and
      one mini-thoracotomy (3-6 cm). The dominant arteries were interrupted, and the
      intersegmental line was identified using IRT with ICG. RESULTS: Identification of
      the intersegmental line was possible in 11 (84.6%) of the 13 patients. The
      average age was 70 years, and 6 of the patients were male. The mean operation
      time was 191 min, and the mean bleeding volume was 64 ml. The operation time and
      bleeding volume were similar to the values in the other 31 patients who underwent
      thoracotomy (167 min/115 ml, P = 0.212/0.361, respectively). No complications
      attributable to IRT with ICG were observed. CONCLUSIONS: VATS segmentectomy using
      IRT with ICG allows the maintenance of a clear surgical view and identification
      of the intersegmental line in a high proportion of cases. Therefore, we consider
      this method to be useful for minimally invasive thoracic surgery.

PMID- 24335268
TI  - Assessment of labile plasma iron in patients who undergo hematopoietic stem cell
      transplantation.
AB  - Body iron disorders have been reported after myeloablative conditioning in
      patients undergoing hematopoietic stem cell transplantation (HSCT). There is a
      concern that labile plasma iron (LPI), the redox-active form of iron, can be
      involved in the occurrence of toxicity and other complications commonly observed
      in the early post-HSCT period. In order to better understand the LPI kinetics and
      its determinants and implications, we undertook sequential LPI determinations
      before and after conditioning until engraftment in 25 auto-HSCT patients.
      Increased LPI was present in only 5 patients before starting conditioning.
      Shortly after conditioning, LPI levels were increased in 23 patients, with peak
      at day 0, returning to normal range upon engraftment in 21 patients. Overall, LPI
      levels correlated weakly with serum ferritin and more strongly with transferrin
      saturation; however, both parameters were apparently not applicable as surrogate
      markers for increased LPI. Although this was a small cohort, logistic regression
      suggested that baseline LPI levels could predict occurrence of grade III or IV
      toxicity. In conclusion, LPI kinetics is influenced by aplasia following
      conditioning and engraftment. Measuring LPI before starting conditioning can
      offer an opportunity to predict toxicity and, perhaps, the need for chelation
      therapy.

PMID- 24335269
TI  - Latitudinal gradients in intraspecific ecological diversity.
AB  - The increase in the number of species with decreasing latitude is a striking
      pattern of global biodiversity. An important feature of studies of this pattern
      up to now has been the focus on species as the fundamental unit of interest,
      neglecting potential within-species ecological diversity. Here, we took a new
      perspective on this topic by measuring the degree to which individuals within
      populations differ in niche attributes across a latitudinal gradient (range:
      54.01 degrees  S to 69.12 degrees  N). We show that 156 populations of 76 species
      across a wide range of vertebrate and invertebrate animal taxa contain more
      ecologically diverse assemblages of individuals towards lower latitudes. Our
      results add a new level of complexity to our understanding of global patterns of
      biodiversity and suggest the possibility that niche variation is partly
      responsible for the latitudinal gradients of species diversity. 

PMID- 24335270
TI  - Relationship between evenness and body size in species rich assemblages.
AB  - Evenness is a key measure of community structure. Here, we examine the
      relationship between evenness and size-abundance distributions for both
      individuals and species using data gathered from Amazonian fish assemblages. We
      show that evenness increases as the fraction of numerically abundant species in
      larger body-size classes rises. As any processes that enable larger bodied
      species to increase their numerical dominance will influence evenness, these
      results help explain why evenness is an important correlate of ecosystem
      function. 

PMID- 24335271
TI  - Chameleons communicate with complex colour changes during contests: different
      body regions convey different information.
AB  - Many animals display static coloration (e.g. of feathers or fur) that can serve
      as a reliable sexual or social signal, but the communication function of rapidly
      changing colours (as in chameleons and cephalopods) is poorly understood. We used
      recently developed photographic and mathematical modelling tools to examine how
      rapid colour changes of veiled chameleons Chamaeleo calyptratus predict
      aggressive behaviour during male-male competitions. Males that achieved brighter
      stripe coloration were more likely to approach their opponent, and those that
      attained brighter head coloration were more likely to win fights; speed of head
      colour change was also an important predictor of contest outcome. This
      correlative study represents the first quantification of rapid colour change
      using organism-specific visual models and provides evidence that the rate of
      colour change, in addition to maximum display coloration, can be an important
      component of communication. Interestingly, the body and head locations of the
      relevant colour signals map onto the behavioural displays given during specific
      contest stages, with lateral displays from a distance followed by directed, head
      on approaches prior to combat, suggesting that different colour change signals
      may evolve to communicate different information (motivation and fighting ability,
      respectively). 

PMID- 24335272
TI  - Preference patterns for skewed gambles in rhesus monkeys.
AB  - While standard models of risky choice account for the first and second
      statistical moments of reward outcome distributions (mean and variance,
      respectively), they often ignore the third moment, skewness. Determining a
      decision-maker's attitude about skewness is useful because it can help constrain
      process models of the mental steps involved in risky choice. We measured three
      rhesus monkeys' preferences for gambles whose outcome distributions had almost
      identical means and variances but differed in skewness. We tested five
      distributions of skewness: strong negative, weak negative, normal, weak positive
      and strong positive. Monkeys preferred positively skewed gambles to negatively
      skewed ones and preferred strongly skewed and normal (i.e. unskewed) gambles to
      weakly skewed ones. This pattern of preferences cannot be explained solely by
      monotonic deformations of the utility curve or any other popular single account,
      but can be accounted for by multiple interacting factors. 

PMID- 24335273
TI  - Performance of the Rockall scoring system in predicting the need for intervention
      and outcomes in patients with nonvariceal upper gastrointestinal bleeding in a
      Brazilian setting: a prospective study.
AB  - BACKGROUND/AIMS: This prospective study investigated the performance of pre
      endoscopy and the complete Rockall scores in predicting the occurrence of adverse
      outcomes and the need for endoscopic or surgical intervention in patients with
      nonvariceal upper gastrointestinal bleeding. METHODS: All 656 consecutive
      patients who underwent endoscopy due to nonvariceal upper gastrointestinal
      bleeding between 2007 and 2011 were included. Receiver operating characteristic
      (ROC) curves were plotted for the outcomes of therapeutic intervention,
      rebleeding and death. The discriminative accuracy of the risk scores was assessed
      by the area under the ROC curve. RESULTS: Endoscopic treatment was performed in
      55.2% of the patients. Rebleeding and mortality rates were 7.6 and 3.8%,
      respectively. The pre-endoscopy Rockall scores showed unsatisfactory accuracy in
      predicting the need for intervention, rebleeding or death, as shown by the
      respective area under the ROC curve values of 0.52, 0.52 and 0.65. The accuracy
      of the complete Rockall score in predicting rebleeding was poor (area under ROC:
      0.52), but it was higher for mortality (area under ROC: 0.69). CONCLUSIONS: The
      pre-endoscopy Rockall score was not useful for predicting the need for
      therapeutic intervention or adverse outcomes. The complete Rockall score showed
      an acceptable performance in predicting mortality, but was unable to predict
      rebleeding.

PMID- 24335274
TI  - The influence of chitin on the immune response to the house dust mite allergen
      Blo T 12.
AB  - BACKGROUND: Information about the biological properties of Blomia tropicalis
      allergens is scarce. It is predicted that Blo t 12, an allergen with two
      described isoforms, contains a chitin-binding domain, similar to that found in
      peritrophins. Th2 adjuvant properties have been described for chitin. Therefore,
      it is feasible that binding to this carbohydrate influences its allergenicity. We
      aimed to evaluate the chitin-binding activity of Blo t 12 isoallergens and its
      effect on airway inflammation and antibody responses in a murine model of
      allergen sensitization. METHODS: Chitin-binding assays were conducted with the
      recombinant isoallergens Blo t 12.0101 and Blo t 12.0102. BALB/c mice were
      sensitized via i.p. with any of the two isoforms (alone, with chitin or alum) and
      then challenged intranasally. Methacholine-induced bronchial hyperreactivity was
      tested by whole-body plethysmography and lung sections were stained with
      hematoxylin and eosin and periodic-acid Schiff. Total IgE and allergen-specific
      IgE, IgG1 and IgG2 levels were measured by ELISA. RESULTS: The two isoforms bound
      chitin, but Blo t 12.0101 showed a stronger binding capacity. Both isoforms
      induced total and allergen-specific IgE, airway hyperreactivity, bronchial
      inflammation and mucus secretion without any adjuvant; however, when administered
      with chitin, Blo t 12.0101 induced higher total IgE levels. The IgG1/IgG2a ratio
      was significantly higher in mice immunized with Blo t 12.0101 than those
      immunized with Blo t 12.0102. As peritrophins, Blo t 12 was detected in mite
      feces. CONCLUSIONS: Blo t 12 isoforms are chitin-binding proteins that induce
      airway inflammation and bronchial hyperreactivity. However, for Blo t 12.0101,
      chitin reinforces its effects on total IgE production.

PMID- 24335275
TI  - ART1 silencing enhances apoptosis of mouse CT26 cells via the PI3K/Akt/NF-kappaB
      pathway.
AB  - BACKGROUND/AIMS: Colorectal carcinoma is one of the most common cancers world
      wide, with high morbidity and mortality rates. Arginine ADP-ribosyltransferase
      1(ART1) is an important ecto-ADP-ribose transferase and has been proven to be
      intimately involved in a number of biological processes. However, the influence
      of ART1 on survival and apoptosis of colorectal carcinoma cells and the potential
      mechanism of action of ART1 remain uncharacterized. METHODS: ART1 was silenced
      via lentiviral vector-mediated short hairpin RNA (shRNA) in CT26 colon carcinoma
      cells, and cisplatin (CDDP) was applied to induce apoptosis. Survival and
      apoptosis rate of CT26 cells was assessed by CCK8 assay, flow cytometry and
      Hoechst 33342 staining. Expression and activity of signaling proteins were
      detected by Western blot. RESULTS: ART1 knockdown enhanced the inhibition of cell
      survival and increased the apoptosis induced by CDDP. Furthermore, the reduced
      survival rate correlated with reduced levels of phos-Akt(Thr308) and phos
      IkappaBalpha and reduced NF-kappaB p65 nuclear translocation. A decline in Bcl-2
      and Bcl-xl expression and an increase in Bax expression may explain the enhanced
      apoptosis. CONCLUSION: This study provides a molecular mechanism for the function
      of ART1 in colorectal carcinoma and defines a potential therapeutic target for
      the enhanced treatment of this prominent world-wide disease.

PMID- 24335276
TI  - Functions of personal experience and of expression of regret.
AB  - Although learning and preparing for future behavior are well-established
      functions of regret, social functions have been largely ignored. We suggest a new
      model of the functions of regret, the Privately Experienced Versus Expressed
      Regret model, in which private experience and public expression differentially
      serve these functions. The current research examined this model using both
      naturalistic and experimental approaches. In Study 1, we coded tweets about
      regret posted on social media to examine whether this content emphasized social
      relationships versus learning and preparation. Study 2 experimentally examined
      the hypothesized social closeness function for expression of regrets. Study 3
      further examined how privately experienced and publicly expressed regrets differ
      on the social closeness and learning and preparatory functions. Studies 4 and 5
      confirmed the specific social closeness function rather than global social
      benefits. This research suggests that the social expression of regret differs
      from private experience in both form and function. 

PMID- 24335277
TI  - Pediatric neurosurgery patients need more than a neurological surgeon: a clinical
      experience.
AB  - The Division of Pediatric Neurosurgery of the University of Florida College of
      Medicine Jacksonville initiated and developed a multidisciplinary comprehensive
      team for the management of patients with a neurosurgical condition other than
      spina bifida. This report relates the rationale and stages of development of a
      multidisciplinary team to facilitate the health care and special needs of these
      children.

PMID- 24335278
TI  - Tip of the iceberg: reporting and gender-based violence in developing countries.
AB  - Gender-based violence (GBV) is widespread globally and has myriad adverse health
      effects but is vastly underreported. Few studies address the extent of reporting
      bias in existing estimates. We provide bounds for underestimation of reporting of
      GBV to formal and informal sources conditional on having experienced GBV and
      characterize differences between women who report and those who do not. We
      analyzed Demographic and Health Survey data from 284,281 women in 24 countries
      collected between 2004 and 2011. We performed descriptive analysis and
      multivariate logistic regressions examining characteristics associated with
      reporting to formal sources. Forty percent of women experiencing GBV previously
      disclosed to someone; however, only 7% reported to a formal source (regional
      variation, 2% in India and East Asia to 14% in Latin America and the Caribbean).
      Formerly married and never married status, urban residence, and increasing age
      were characteristics associated with increased likelihood of formal reporting.
      Our results imply that estimates of GBV prevalence based on health systems data
      or on police reports may underestimate the total prevalence of GBV, ranging from
      11- to 128-fold, depending on the region and type of reporting. In addition,
      women who report GBV differ from those who do not, with implications for program
      targeting and design of interventions. 

PMID- 24335279
TI  - Functional domains of the 50S subunit mature late in the assembly process.
AB  - Despite the identification of many factors that facilitate ribosome assembly, the
      molecular mechanisms by which they drive ribosome biogenesis are poorly
      understood. Here, we analyze the late stages of assembly of the 50S subunit using
      Bacillus subtilis cells depleted of RbgA, a highly conserved GTPase. We found
      that RbgA-depleted cells accumulate late assembly intermediates bearing sub
      stoichiometric quantities of ribosomal proteins L16, L27, L28, L33a, L35 and L36.
      Using a novel pulse labeling/quantitative mass spectrometry technique, we show
      that this particle is physiologically relevant and is capable of maturing into a
      complete 50S particle. Cryo-electron microscopy and chemical probing revealed
      that the central protuberance, the GTPase associating region and tRNA-binding
      sites in this intermediate are unstructured. These findings demonstrate that key
      functional sites of the 50S subunit remain unstructured until late stages of
      maturation, preventing the incomplete subunit from prematurely engaging in
      translation. Finally, structural and biochemical analysis of a ribosome particle
      depleted of L16 indicate that L16 binding is necessary for the stimulation of
      RbgA GTPase activity and, in turn, release of this co-factor, and for conversion
      of the intermediate to a complete 50S subunit. 

PMID- 24335280
TI  - Molecular evolution of protein-RNA mimicry as a mechanism for translational
      control.
AB  - Elongation factor P (EF-P) is a conserved ribosome-binding protein that
      structurally mimics tRNA to enable the synthesis of peptides containing motifs
      that otherwise would induce translational stalling, including polyproline. In
      many bacteria, EF-P function requires post-translational modification with (R)
      beta-lysine by the lysyl-tRNA synthetase paralog PoxA. To investigate how
      recognition of EF-P by PoxA evolved from tRNA recognition by aminoacyl-tRNA
      synthetases, we compared the roles of EF-P/PoxA polar contacts with analogous
      interactions in a closely related tRNA/synthetase complex. PoxA was found to
      recognize EF-P solely via identity elements in the acceptor loop, the domain of
      the protein that interacts with the ribosome peptidyl transferase center and
      mimics the 3'-acceptor stem of tRNA. Although the EF-P acceptor loop residues
      required for PoxA recognition are highly conserved, their conservation was found
      to be independent of the phylogenetic distribution of PoxA. This suggests EF-P
      first evolved tRNA mimicry to optimize interactions with the ribosome, with PoxA
      catalyzed aminoacylation evolving later as a secondary mechanism to further
      improve ribosome binding and translation control. 

PMID- 24335281
TI  - Genetic analysis of the Replication Protein A large subunit family in Arabidopsis
      reveals unique and overlapping roles in DNA repair, meiosis and DNA replication.
AB  - Replication Protein A (RPA) is a heterotrimeric protein complex that binds single
      stranded DNA. In plants, multiple genes encode the three RPA subunits (RPA1, RPA2
      and RPA3), including five RPA1-like genes in Arabidopsis. Phylogenetic analysis
      suggests two distinct groups composed of RPA1A, RPA1C, RPA1E (ACE group) and
      RPA1B, RPA1D (BD group). ACE-group members are transcriptionally induced by
      ionizing radiation, while BD-group members show higher basal transcription and
      are not induced by ionizing radiation. Analysis of rpa1 T-DNA insertion mutants
      demonstrates that although each mutant line is likely null, all mutant lines are
      viable and display normal vegetative growth. The rpa1c and rpa1e single mutants
      however display hypersensitivity to ionizing radiation, and combination of rpa1c
      and rpa1e results in additive hypersensitivity to a variety of DNA damaging
      agents. Combination of the partially sterile rpa1a with rpa1c results in complete
      sterility, incomplete synapsis and meiotic chromosome fragmentation, suggesting
      an early role for RPA1C in promoting homologous recombination. Combination of
      either rpa1c and/or rpa1e with atr revealed additive hypersensitivity phenotypes
      consistent with each functioning in unique repair pathways. In contrast, rpa1b
      rpa1d double mutant plants display slow growth and developmental defects under
      non-damaging conditions. We show these defects in the rpa1b rpa1d mutant are
      likely the result of defective DNA replication leading to reduction in cell
      division. 

PMID- 24335282
TI  - Analysis of the SWI/SNF chromatin-remodeling complex during early heart
      development and BAF250a repression cardiac gene transcription during P19 cell
      differentiation.
AB  - The regulatory networks of differentiation programs and the molecular mechanisms
      of lineage-specific gene regulation in mammalian embryos remain only partially
      defined. We document differential expression and temporal switching of BRG1
      associated factor (BAF) subunits, core pluripotency factors and cardiac-specific
      genes during post-implantation development and subsequent early organogenesis.
      Using affinity purification of BRG1 ATPase coupled to mass spectrometry, we
      characterized the cardiac-enriched remodeling complexes present in E8.5 mouse
      embryos. The relative abundance and combinatorial assembly of the BAF subunits
      provides functional specificity to Switch/Sucrose NonFermentable (SWI/SNF)
      complexes resulting in a unique gene expression profile in the developing heart.
      Remarkably, the specific depletion of the BAF250a subunit demonstrated
      differential effects on cardiac-specific gene expression and resulted in
      arrhythmic contracting cardiomyocytes in vitro. Indeed, the BAF250a physically
      interacts and functionally cooperates with Nucleosome Remodeling and Histone
      Deacetylase (NURD) complex subunits to repressively regulate chromatin structure
      of the cardiac genes by switching open and poised chromatin marks associated with
      active and repressed gene expression. Finally, BAF250a expression modulates BRG1
      occupancy at the loci of cardiac genes regulatory regions in P19 cell
      differentiation. These findings reveal specialized and novel cardiac-enriched
      SWI/SNF chromatin-remodeling complexes, which are required for heart formation
      and critical for cardiac gene expression regulation at the early stages of heart
      development. 

PMID- 24335283
TI  - The influence of viral RNA secondary structure on interactions with innate host
      cell defences.
AB  - RNA viruses infecting vertebrates differ fundamentally in their ability to
      establish persistent infections with markedly different patterns of transmission,
      disease mechanisms and evolutionary relationships with their hosts. Although
      interactions with host innate and adaptive responses are complex and persistence
      mechanisms likely multi-factorial, we previously observed associations between
      bioinformatically predicted RNA secondary formation in genomes of positive
      stranded RNA viruses with their in vivo fitness and persistence. To analyse this
      interactions functionally, we transfected fibroblasts with non-replicating, non
      translated RNA transcripts from RNA viral genomes with differing degrees of
      genome-scale ordered RNA structure (GORS). Single-stranded RNA transcripts
      induced interferon-beta mediated though RIG-I and PKR activation, the latter
      associated with rapid induction of antiviral stress granules. A striking inverse
      correlation was observed between induction of both cellular responses with
      transcript RNA structure formation that was independent of both nucleotide
      composition and sequence length. The consistent inability of cells to recognize
      RNA transcripts possessing GORS extended to downstream differences from
      unstructured transcripts in expression of TNF-alpha, other interferon-stimulated
      genes and induction of apoptosis. This functional association provides novel
      insights into interactions between virus and host early after infection and
      provides evidence for a novel mechanism for evading intrinsic and innate immune
      responses. 

PMID- 24335284
TI  - Transcriptional regulation by BglJ-RcsB, a pleiotropic heteromeric activator in
      Escherichia coli.
AB  - The bacterial Rcs phosphorelay signals perturbations of the bacterial cell
      envelope to its response regulator RcsB, which regulates transcription of
      multiple loci related to motility, biofilm formation and various stress
      responses. RcsB is unique, as its set of target loci is modulated by interaction
      with auxiliary regulators including BglJ. The BglJ-RcsB heteromer is known to
      activate the HNS repressed leuO and bgl loci independent of RcsB phosphorylation.
      Here, we show that BglJ-RcsB activates the promoters of 10 additional loci (chiA,
      molR, sfsB, yecT, yqhG, ygiZ, yidL, ykiA, ynbA and ynjI). Furthermore, we mapped
      the BglJ-RcsB binding site at seven loci and propose a consensus sequence motif.
      The data suggest that activation by BglJ-RcsB is DNA phasing dependent at some
      loci, a feature reminiscent of canonical transcriptional activators, while at
      other loci BglJ-RcsB activation may be indirect by inhibition of HNS-mediated
      repression. In addition, we show that BglJ-RcsB activates transcription of bgl
      synergistically with CRP where it shifts the transcription start by 20 bp from a
      position typical for class I CRP-dependent promoters to a position typical for
      class II CRP-dependent promoters. Thus, BglJ-RcsB is a pleiotropic
      transcriptional activator that coordinates regulation with global regulators
      including CRP, LeuO and HNS. 

PMID- 24335286
TI  - Evasion of antiviral immunity through sequestering of TBK1/IKKepsilon/IRF3 into
      viral inclusion bodies.
AB  - Cells are equipped with pattern recognition receptors (PRRs) such as the Toll
      like and RIG-I-like receptors that mount innate defenses against viruses.
      However, viruses have evolved multiple strategies to evade or thwart host
      antiviral responses. Viral inclusion bodies (IBs), which are accumulated
      aggregates of viral proteins, are commonly formed during the replication of some
      viruses in infected cells, but their role in viral immune evasion has rarely been
      explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging
      febrile illness caused by a novel phlebovirus in the Bunyaviridae. The SFTS viral
      nonstructural protein NSs can suppress host beta interferon (IFN-beta) responses.
      NSs can form IBs in infected and transfected cells. Through interaction with tank
      binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex,
      including IKKepsilon and IRF3, into IBs, although NSs did not interact with
      IKKepsilon or IRF3 directly. When cells were infected with influenza A virus,
      IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated
      into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but
      p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-beta induction
      and enhanced viral replication. Sequestration of the IKK complex and active IRF3
      into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for
      viral evasion of innate immunity. 

PMID- 24335285
TI  - Human 4E-T represses translation of bound mRNAs and enhances microRNA-mediated
      silencing.
AB  - A key player in translation initiation is eIF4E, the mRNA 5' cap-binding protein.
      4E-Transporter (4E-T) is a recently characterized eIF4E-binding protein, which
      regulates specific mRNAs in several developmental model systems. Here, we first
      investigated the role of its enrichment in P-bodies and eIF4E-binding in
      translational regulation in mammalian cells. Identification of the conserved C
      terminal sequences that target 4E-T to P-bodies was enabled by comparison of
      vertebrate proteins with homologues in Drosophila (Cup and CG32016) and
      Caenorhabditis elegans by sequence and cellular distribution. In tether function
      assays, 4E-T represses bound mRNA translation, in a manner independent of these
      localization sequences, or of endogenous P-bodies. Quantitative polymerase chain
      reaction and northern blot analysis verified that bound mRNA remained intact and
      polyadenylated. Ectopic 4E-T reduces translation globally in a manner dependent
      on eIF4E binding its consensus Y30X4L site. In contrast, tethered 4E-T continued
      to repress translation when eIF4E-binding was prevented by mutagenesis of YX4L,
      and modestly enhanced the decay of bound mRNA, compared with wild-type 4E-T,
      mediated by increased binding of CNOT1/7 deadenylase subunits. As depleting 4E-T
      from HeLa cells increased steady-state translation, in part due to relief of
      microRNA-mediated silencing, this work demonstrates the conserved yet
      unconventional mechanism of 4E-T silencing of particular subsets of mRNAs.

PMID- 24335287
TI  - Lysis delay and burst shrinkage of coliphage T7 by deletion of terminator Tphi
      reversed by deletion of early genes.
AB  - Bacteriophage T7 terminator Tphi is a class I intrinsic terminator coding for an
      RNA hairpin structure immediately followed by oligo(U), which has been
      extensively studied in terms of its transcription termination mechanism, but
      little is known about its physiological or regulatory functions. In this study,
      using a T7 mutant phage, where a 31-bp segment of Tphi was deleted from the
      genome, we discovered that deletion of Tphi from T7 reduces the phage burst size
      but delays lysis timing, both of which are disadvantageous for the phage. The
      burst downsizing could directly result from Tphi deletion-caused upregulation of
      gene 17.5, coding for holin, among other Tphi downstream genes, because infection
      of gp17.5-overproducing Escherichia coli by wild-type T7 phage showed similar
      burst downsizing. However, the lysis delay was not associated with cellular
      levels of holin or lysozyme or with rates of phage adsorption. Instead, when
      allowed to evolve spontaneously in five independent adaptation experiments, the
      Tphi-lacking mutant phage, after 27 or 29 passages, recovered both burst size and
      lysis time reproducibly by deleting early genes 0.5, 0.6, and 0.7 of class I,
      among other mutations. Deletion of genes 0.5 to 0.7 from the Tphi-lacking mutant
      phage decreased expression of several Tphi downstream genes to levels similar to
      that of the wild-type phage. Accordingly, phage T7 lysis timing is associated
      with cellular levels of Tphi downstream gene products. This suggests the
      involvement of unknown factor(s) besides the known lysis proteins, lysozyme and
      holin, and that Tphi plays a role of optimizing burst size and lysis time during
      T7 infection. IMPORTANCE Bacteriophages are bacterium-infecting viruses. After
      producing numerous progenies inside bacteria, phages lyse bacteria using their
      lysis protein(s) to get out and start a new infection cycle. Normally, lysis is
      tightly controlled to ensure phage progenies are maximally produced and released
      at an optimal time. Here, we have discovered that phage T7, besides employing its
      known lysis proteins, additionally uses its transcription terminator Tphi to
      guarantee the optimal lysis of the E. coli host. Tphi, positioned in the middle
      of the T7 genome, must be inactivated at least partially to allow for
      transcription-driven translocation of T7 DNA into hosts and expression of Tphi
      downstream but promoter-lacking genes. What role is played by Tphi before
      inactivation? Without Tphi, not only was lysis time delayed but also the number
      of progenies was reduced in this study. Furthermore, T7 can overcome Tphi
      deletion by further deleting some genes, highlighting that a phage has multiple
      strategies for optimizing lysis. 

PMID- 24335288
TI  - Innate immune response induced by baculovirus attenuates transgene expression in
      mammalian cells.
AB  - The baculovirus Autographa californica nucleopolyhedrovirus (AcNPV) has been
      widely used to achieve a high level of foreign gene expression in insect cells,
      as well as for efficient gene transduction into mammalian cells without any
      replication. In addition to permitting efficient gene delivery, baculovirus has
      been shown to induce host innate immune responses in various mammalian cells and
      in mice. In this study, we examined the effects of the innate immune responses on
      gene expression by recombinant baculoviruses in cultured cells. The reporter gene
      expression in IRF3-deficient mouse embryonic fibroblasts (MEFs) infected with the
      recombinant baculovirus was shown to be enhanced in accordance with the
      suppression of beta interferon (IFN-beta) production. Furthermore, efficient gene
      transduction by the recombinant baculovirus was achieved in MEFs deficient for
      stimulator of interferon genes (STING), TANK binding kinase 1 (TBK1), IFN
      regulatory factor 3 (IRF3), or IFN-beta promoter stimulator 1 (IPS-1), but not in
      those deficient for IRF7, MyD88, or Z-DNA binding protein 1 (ZBP1)/DAI.
      Enhancement of gene expression by the recombinant baculovirus was also observed
      in human hepatoma cell lines replicating hepatitis C virus (HCV), in which innate
      immunity was impaired by the cleavage of IPS-1 by the viral protease. In
      addition, infection with the recombinant baculovirus expressing the BH3-only
      protein, BIMS, a potent inducer of apoptosis, resulted in a selective cell death
      in the HCV replicon cells. These results indicate that innate immune responses
      induced by infection with baculovirus attenuate transgene expression, and this
      characteristic might be useful for a selective gene transduction into cells with
      impaired innate immunity arising from infection with various viruses. 

PMID- 24335290
TI  - Novel hybrid parvovirus-like virus, NIH-CQV/PHV, contaminants in silica column
      based nucleic acid extraction kits.

PMID- 24335289
TI  - Differential responses of disease-resistant and disease-susceptible primate
      macrophages and myeloid dendritic cells to simian hemorrhagic fever virus
      infection.
AB  - Simian hemorrhagic fever virus (SHFV) causes a fatal hemorrhagic fever in
      macaques but an asymptomatic, persistent infection in baboons. To investigate
      factors contributing to this differential infection outcome, the targets of SHFV
      infection, macrophages (MPhis) and myeloid dendritic cells (mDCs), were
      differentiated from macaque and baboon peripheral blood monocytes and used to
      compare viral replication and cell responses. SHFV replicated in >90% of macaque
      MPhis but in only ~10% of baboon MPhis. Although SHFV infected ~50% of macaque
      and baboon mDCs, virus replication was efficient in macaque but not in baboon
      mDCs. Both types of macaque cultures produced higher virus yields than baboon
      cultures. A more efficient type I interferon response and the production of
      proinflammatory cytokines, including interleukin-1beta (IL-1beta), IL-6, IL
      12/23(p40), tumor necrosis factor alpha (TNF-alpha), and macrophage inflammatory
      protein 1alpha (MIP-1alpha), in response to SHFV infection were observed in
      macaque but not baboon cultures, suggesting less efficient counteraction of these
      responses by viral proteins in macaque cells. Baboon cultures produced higher
      levels of IL-10 than macaque cultures both prior to and after SHFV infection. In
      baboon but not macaque cell cultures, SHFV infection upregulated IL-10R1, a
      subunit of the IL-10 receptor (IL-10R), and also SOCS3, a negative regulator of
      proinflammatory cytokine production. Incubation of macaque cultures with human IL
      10 before and/or after SHFV infection decreased production of IL-6, IL-1beta, and
      MIP-1alpha but not TNF-alpha, suggesting a role for IL-10 in suppressing SHFV
      induced proinflammatory cytokine production in macaques. 

PMID- 24335291
TI  - Infection of myofibers contributes to increased pathogenicity during infection
      with an epidemic strain of chikungunya virus.
AB  - Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that is
      known to cause severe arthritis and myositis in affected patients. The ongoing
      epidemic began in eastern Africa in 2004 and then spread to islands of the Indian
      Ocean, India, and Southeast Asia, ultimately afflicting millions. During this
      outbreak, more severe disease manifestations, including fatalities, have been
      documented. The reasons for this change in pathogenesis are multifactorial but
      likely include mutations that have arisen in the viral genome which could alter
      disease pathogenesis. To test this hypothesis, we used a murine model of CHIKV to
      compare the disease pathogeneses of two recombinant strains of CHIKV, the first
      derived from the La Reunion outbreak in 2006 (LR2006 OPY1) and the second
      isolated from Senegal in 1983 (37997). While the two strains exhibited similar
      growth in mammalian cells in vitro, we observed more severe clinical disease and
      pathology in mice infected with the LR2006 OPY1 strain of CHIKV, which included
      prolonged viremia and elevated viral titers and persistence in the muscle,
      resulting in devastating myonecrosis. Both CHIKV strains infected connective
      tissue fibroblasts of the muscle, but only the LR2006 OPY1 strain replicated
      within myofibers in vivo, despite similar growth of the two strains in these cell
      types in vitro. However, when the 37997 strain was administered directly into
      muscle, myofiber infection was comparable to that in LR2006 OPY1-infected mice.
      These results indicate that differences in the ability of the strain of CHIKV to
      establish infection in myofibers may contribute to the increased disease
      severity. IMPORTANCE: CHIKV is an emerging pathogen that causes significant
      morbidity. Little is known about the pathogenesis of the disease, and this study
      suggests that the ability of a recent epidemic strain to infect myofibers results
      in increased disease severity. Better understanding of how CHIKV causes disease
      contributes to the ultimate goal of creating therapeutics to alleviate the impact
      of this debilitating virus.

PMID- 24335292
TI  - Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate.
AB  - The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant
      between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40%
      in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing
      immunity against Lassa virus challenge in guinea pigs and marmosets and virus
      specific cell-mediated immunity in both simian immunodeficiency virus (SIV)
      infected and uninfected rhesus macaques. Here, we show that ML29 is stable after
      12 passages in vitro without losing its plaque morphology or its attenuated
      phenotype in suckling mice. Additionally, we used deep sequencing to characterize
      the viral population comprising the original stock of ML29, the stock of ML29
      after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated
      animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20%
      of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these
      77 mutations, 5 appeared to be host specific, for example, appearing in mice but
      not in primates. None of these mutations were reversions of ML29 to the sequences
      of the parental Lassa and Mopeia viruses. The host-specific mutations indicate
      viral adaptations to virus-host interactions, and such interactions make
      reasonable targets for antiviral approaches. Variants capable of chronic
      infection did not emerge from any of the primate infections, even in immune
      deficient animals, indicating that the ML29 reassortant is reasonably stable in
      vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine
      candidate have been advanced, showing high levels of protection in nonhuman
      primates and acceptable stability both in vitro and in vivo. 

PMID- 24335293
TI  - In vivo SELEX of single-stranded domains in the HIV-1 leader RNA.
AB  - The 5' untranslated leader region of the human immunodeficiency virus type 1 (HIV
      1) RNA genome is a strongly conserved sequence that encodes several regulatory
      motifs important for viral replication. Most of these motifs are exposed as
      hairpin structures, including the dimerization initiation signal (DIS), the major
      splice donor site (SD), and the packaging signal (Psi), which are connected by
      short single-stranded regions. Mutational analysis revealed many functions of
      these hairpins, but only a few studies have focused on the single-stranded purine
      rich sequences. Using the in vivo SELEX (systematic evolution of ligands by
      exponential enrichment) approach, we probed the sequence space in these regions
      that is compatible with efficient HIV-1 replication and analyzed the impact on
      the RNA secondary structure of the leader RNA. Our results show a strong sequence
      requirement for the DIS hairpin flanking regions. We postulate that these
      sequences are important for the binding of specific protein factors that support
      leader RNA-mediated functions. The sequence between the SD and Psi hairpins seems
      to have a less prominent role, despite the strong conservation of the stretch of
      5 A residues in natural isolates. We hypothesize that this may reflect the subtle
      evolutionary pressure on HIV-1 to acquire an A-rich RNA genome. In silico
      analyses indicate that sequences are avoided in all 3 single-stranded domains
      that affect the local or overall leader RNA folding. IMPORTANCE Many regulatory
      RNA sequences are clustered in the untranslated leader domain of the HIV-1 RNA
      genome. Several RNA hairpin structures in this domain have been proposed to
      fulfill specific roles, e.g., mediating RNA dimer formation to facilitate HIV-1
      recombination. We now focus on the importance of a few well-conserved single
      stranded sequences that connect these hairpins. We created libraries of HIV-1
      variants in which these segments were randomized and selected the best
      replicating variants. For two segments we document the selection of the (nearly)
      wild-type sequence, thus demonstrating the importance of these primary nucleotide
      sequences and the power of the in vivo SELEX approach. However, for the third
      segment a large variety of sequences is compatible with efficient HIV-1
      replication. Interestingly, the A-rich sequence of this segment is highly
      conserved among HIV-1 isolates, which likely reflects the evolutionary tendency
      of HIV-1 to adopt A-rich sequences. 

PMID- 24335294
TI  - Hantavirus Gn and Gc glycoproteins self-assemble into virus-like particles.
AB  - How hantaviruses assemble and exit infected cells remains largely unknown. Here,
      we show that the expression of Andes (ANDV) and Puumala (PUUV) hantavirus Gn and
      Gc envelope glycoproteins lead to their self-assembly into virus-like particles
      (VLPs) which were released to cell supernatants. The viral nucleoprotein was not
      required for particle formation. Further, a Gc endodomain deletion mutant did not
      abrogate VLP formation. The VLPs were pleomorphic, exposed protrusions and
      reacted with patient sera. 

PMID- 24335295
TI  - The Kaposi's sarcoma-associated herpesvirus (KSHV)-induced 5-lipoxygenase
      leukotriene B4 cascade plays key roles in KSHV latency, monocyte recruitment, and
      lipogenesis.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with
      Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). KS lesions are
      characterized by endothelial cells with multiple copies of the latent KSHV
      episomal genome, lytic replication in a low percentage of infiltrating monocytes,
      and inflammatory cytokines plus growth factors. We demonstrated that KSHV
      utilizes inflammatory cyclooxygenase 2/prostaglandin E2 to establish and maintain
      latency (Sharma-Walia, N., A. G. Paul, V. Bottero, S. Sadagopan, M. V. Veettil,
      N. Kerur, and B. Chandran, PLoS Pathog 6:e1000777, 2010
      [doi:10.1371/journal.ppat.1000777]). Here, we evaluated the role of 5
      lipoxygenase (5LO) and its chemotactic metabolite leukotriene B4 (LTB4) in KSHV
      biology. Abundant staining of 5LO was detected in human KS tissue sections. We
      observed elevated levels of 5LO and high levels of secretion of LTB4 during
      primary KSHV infection of endothelial cells and in PEL B cells (BCBL-1 and BC-3
      cells). Blocking the 5LO/LTB4 cascade inhibited viral latent ORF73,
      immunomodulatory K5, viral macrophage inflammatory protein 1 (MIP-1), and viral
      MIP-2 gene expression, without much effect on lytic switch ORF50, immediate early
      lytic K8, and viral interferon-regulatory factor 2 gene expression. 5LO
      inhibition significantly downregulated latent viral Cyclin and latency-associated
      nuclear antigen 2 levels in PEL cells. 5LO/LTB4 inhibition downregulated TH2
      related cytokine secretion, elevated TH1-related cytokine secretion, and reduced
      human monocyte recruitment, adhesion, and transendothelial migration. 5LO/LTB4
      inhibition reduced fatty acid synthase (FASN) promoter activity and its
      expression. Since FASN, a key enzyme required in lipogenesis, is important in
      KSHV latency, these findings collectively suggest that 5LO/LTB4 play important
      roles in KSHV biology and that effective inhibition of the 5LO/LTB4 pathway could
      potentially be used in treatment to control KS/PEL. 

PMID- 24335296
TI  - Deletion of the human cytomegalovirus US17 gene increases the ratio of genomes
      per infectious unit and alters regulation of immune and endoplasmic reticulum
      stress response genes at early and late times after infection.
AB  - Human cytomegalovirus (HCMV) employs numerous strategies to combat, subvert, or
      co-opt host immunity. One evolutionary strategy for this involves capture of a
      host gene and then its successive duplication and divergence, forming a family of
      genes, many of which have immunomodulatory activities. The HCMV US12 family
      consists of 10 tandemly arranged sequence-related genes in the unique short (US)
      region of the HCMV genome (US12 to US21). Each gene encodes a protein possessing
      seven predicted transmembrane domains, patches of sequence similarity with
      cellular G-protein-coupled receptors, and the Bax inhibitor 1 family of
      antiapoptotic proteins. We show that one member, US17, plays an important role
      during virion maturation. Microarray analysis of cells infected with a
      recombinant HCMV isolate with a US17 deletion (the DeltaUS17 mutant virus)
      revealed blunted host innate and interferon responses at early times after
      infection (12 h postinfection [hpi]), a pattern opposite that previously seen in
      the absence of the immunomodulatory tegument protein pp65 (pUL83). Although the
      DeltaUS17 mutant virus produced numbers of infectious particles in fibroblasts
      equal to the numbers produced by the parental virus, it produced >3-fold more
      genome-containing noninfectious viral particles and delivered increased amounts
      of pp65 to newly infected cells. These results suggest that US17 has evolved to
      control virion composition, to elicit an appropriately balanced host immune
      response. At later time points (96 hpi), DeltaUS17 mutant-infected cells
      displayed aberrant expression of several host endoplasmic reticulum stress
      response genes and chaperones, some of which are important for the final stages
      of virion assembly and egress. Our results suggest that US17 modulates host
      pathways to enable production of virions that elicit an appropriately balanced
      host immune response. 

PMID- 24335297
TI  - Interferon-stimulated poly(ADP-Ribose) polymerases are potent inhibitors of
      cellular translation and virus replication.
AB  - The innate immune response is the first line of defense against most viral
      infections. Its activation promotes cell signaling, which reduces virus
      replication in infected cells and leads to induction of the antiviral state in
      yet-uninfected cells. This inhibition of virus replication is a result of the
      activation of a very broad spectrum of specific cellular genes, with each of
      their products usually making a small but detectable contribution to the overall
      antiviral state. The lack of a strong, dominant function for each gene product
      and the ability of many viruses to interfere with the development of the
      antiviral response strongly complicate identification of the antiviral activity
      of the activated individual cellular genes. However, we have previously developed
      and applied a new experimental system which allows us to define a critical
      function of some members of the poly(ADP-ribose) polymerase (PARP) family in
      clearance of Venezuelan equine encephalitis virus mutants from infected cells. In
      this new study, we demonstrate that PARP7, PARP10, and the long isoform of PARP12
      (PARP12L) function as important and very potent regulators of cellular
      translation and virus replication. The translation inhibition and antiviral
      effect of PARP12L appear to be mediated by more than one protein function and are
      a result of its direct binding to polysomes, complex formation with cellular RNAs
      (which is determined by both putative RNA-binding and PARP domains), and
      catalytic activity. IMPORTANCE The results of this study demonstrate that
      interferon-stimulated gene products PARP7, PARP10, and PARP12L are potent
      inhibitors of the replication of Venezuelan equine encephalitis virus and other
      alphaviruses. The inhibitory functions are determined by more than a single
      mechanism, and one of them is based on the ability of these proteins to regulate
      cellular translation. Interference with the cellular translational machinery
      depends on the integrity of both the amino-terminal domain, containing a number
      of putative RNA-binding motifs, and the catalytic function of the carboxy
      terminal PARP domain. The PARP-induced changes in translation efficiency appear
      to have a more potent effect on the synthesis of virus-specific proteins than on
      that of cellular proteins, thus making PARP-specific translational downregulation
      an important contributor to the overall development of the antiviral response. 

PMID- 24335298
TI  - Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4
      (vIRF4) targets expression of cellular IRF4 and the Myc gene to facilitate lytic
      replication.
AB  - Besides an essential transcriptional factor for B cell development and function,
      cellular interferon regulatory factor 4 (c-IRF4) directly regulates expression of
      the c-Myc gene, which is not only associated with various B cell lymphomas but
      also required for herpesvirus latency and pathogenesis. Kaposi's sarcoma
      associated herpesvirus (KSHV), the etiological agent of Kaposi's sarcoma and
      primary effusion lymphoma, has developed a unique mechanism to deregulate host
      antiviral innate immunity and growth control by incorporating four viral homologs
      (vIRF1 to -4) of cellular IRFs into its genome. Previous studies have shown that
      several KSHV latent proteins, including vIRF3, vFLIP, and LANA, target the
      expression, function, and stability of c-Myc to establish and maintain viral
      latency. Here we report that the KSHV vIRF4 lytic protein robustly suppresses
      expression of c-IRF4 and c-Myc, reshaping host gene expression profiles to
      facilitate viral lytic replication. Genomewide gene expression analysis revealed
      that KSHV vIRF4 grossly affects host gene expression by upregulating and
      downregulating 118 genes and 166 genes, respectively, by at least 2-fold.
      Remarkably, vIRF4 suppressed c-Myc expression by 11-fold, which was directed
      primarily by the deregulation of c-IRF4 expression. Real-time quantitative PCR
      (RT-qPCR), single-molecule in situ hybridization, and chromatin
      immunoprecipitation assays showed that vIRF4 not only reduces c-IRF4 expression
      but also competes with c-IRF4 for binding to the specific promoter region of the
      c-Myc gene, resulting in drastic suppression of c-Myc expression. Consequently,
      the loss of vIRF4 function in the suppression of c-IRF4 and c-Myc expression
      ultimately led to a reduction of KSHV lytic replication capacity. These results
      indicate that the KSHV vIRF4 lytic protein comprehensively targets the expression
      and function of c-IRF4 to downregulate c-Myc expression, generating a favorable
      environment for viral lytic replication. Finally, this study further reinforces
      the important role of the c-Myc gene in KSHV lytic replication and latency. 

PMID- 24335299
TI  - Ablation of nectin4 binding compromises CD46 usage by a hybrid vesicular
      stomatitis virus/measles virus.
AB  - Measles virus (MV) immunosuppression is due to infection of SLAM-positive immune
      cells, whereas respiratory shedding and virus transmission are due to infection
      of nectin4-positive airway epithelial cells. The vaccine lineage MV strain
      Edmonston (MV-Edm) acquired an additional tropism for CD46 which is the basis of
      its oncolytic specificity. VSVFH is a vesicular stomatitis virus (VSV) encoding
      the MV-Edm F and H entry proteins in place of G. The virus spreads faster than MV
      Edm and is highly fusogenic and a potent oncolytic. To determine whether ablating
      nectin4 tropism from VSVFH might prevent shedding, increasing its safety profile
      as an oncolytic, or might have any effect on CD46 binding, we generated VSVFH
      viruses with H mutations that disrupt attachment to SLAM and/or nectin4.
      Disruption of nectin4 binding reduced release of VSVFH from the basolateral side
      of differentiated airway epithelia composed of Calu-3 cells. However, because
      nectin4 and CD46 have substantially overlapping receptor binding surfaces on H,
      disruption of nectin4 binding compromised CD46 binding and greatly diminished the
      oncolytic potency of these viruses on human cancer cells. Thus, our results
      support continued preclinical development of VSVFH without ablation of nectin4
      binding. 

PMID- 24335300
TI  - Unification of the globally distributed spindle-shaped viruses of the Archaea.
AB  - Viruses with spindle-shaped virions are abundant in diverse environments. Over
      the years, such viruses have been isolated from a wide range of archaeal hosts.
      Evolutionary relationships between them remained enigmatic, however. Here, using
      structural proteins as markers, we define familial ties among these "dark horses"
      of the virosphere and segregate all spindle-shaped viruses into two distinct
      evolutionary lineages, corresponding to Bicaudaviridae and Fuselloviridae. Our
      results illuminate the utility of structure-based virus classification and bring
      additional order to the virosphere. 

PMID- 24335301
TI  - Encephalomyocarditis virus leader is phosphorylated by CK2 and syk as a
      requirement for subsequent phosphorylation of cellular nucleoporins.
AB  - Encephalomyocarditis virus and Theilovirus are species in the Cardiovirus genus
      of the Picornaviridae family. For all cardioviruses, the viral polyprotein is
      initiated with a short Leader (L) protein unique to this genus. The nuclear
      magnetic resonance (NMR) structure of LE from encephalomyocarditis virus (EMCV)
      has been determined. The protein has an NH2-proximal CHCC zinc finger, a central
      linker, and a contiguous, highly acidic motif. The theiloviruses encode the same
      domains, with one or two additional, COOH-proximal domains, characteristic of the
      human Saffold viruses (SafV) and Theiler's murine encephalomyelitis viruses
      (TMEV), respectively. The expression of a cardiovirus L, in recombinant form, or
      during infection/transfection, triggers an extensive, cell-dependent, antihost
      phosphorylation cascade, targeting nucleoporins (Nups) that form the hydrophobic
      core of nuclear pore complexes (NPC). The consequent inhibition of active
      nucleocytoplasmic trafficking is potent and prevents the host from mounting an
      effective antiviral response. For this inhibition, the L proteins themselves must
      be phosphorylated. In cells (extracts or recombinant form), LE was shown to be
      phosphorylated at Thr47 and Tyr41. The first reaction (Thr47), catalyzed by
      casein kinase 2 (CK2), is an obligatory precedent to the second event (Tyr41),
      catalyzed by spleen tyrosine kinase (Syk). Site mutations in LE, or kinase
      specific inhibitors, prevented LE phosphorylation and subsequent Nup
      phosphorylation. Parallel experiments with LS (SafV-2) and LT (TMEV BeAn)
      proteins confirmed the general cardiovirus requirement for L phosphorylation, but
      CK2 was not the culpable kinase. It is likely that LS and LT are both activated
      by alternative kinases in different cell types, probably reactive within the
      Theilo-specific domains. IMPORTANCE An understanding of the diverse methods used
      by viruses to interfere with cellular processes is important because they can
      teach us how to control virus infections. This report shows how viruses in the
      same genus use different cellular enzymes to phosphorylate their proteins. If
      these processes are interfered with, the viruses are severely disabled. 

PMID- 24335302
TI  - Use of IRF-3 and/or IRF-7 knockout mice to study viral pathogenesis: lessons from
      a murine retrovirus-induced AIDS model.
AB  - Interferon regulatory factor (IRF) regulation of the type I interferon response
      has not been extensively explored in murine retroviral infections. IRF-3(-/-) and
      select IRF-3/7(-/-) mice were resistant to LP-BM5-induced pathogenesis. However,
      further analyses strongly suggested that resistance could be attributed to strain
      129-specific contamination of the known retrovirus resistance gene Fv1.
      Therefore, caution should be taken when interpreting phenotypes observed in these
      knockout mice, as strain 129-derived genetic polymorphisms may explain observed
      differences. 

PMID- 24335303
TI  - Utility of humanized BLT mice for analysis of dengue virus infection and
      antiviral drug testing.
AB  - Dengue virus (DENV) is the cause of a potentially life-threatening disease that
      affects millions of people worldwide. The lack of a small animal model that
      mimics the symptoms of DENV infection in humans has slowed the understanding of
      viral pathogenesis and the development of therapies and vaccines. Here, we
      investigated the use of humanized "bone marrow liver thymus" (BLT) mice as a
      model for immunological studies and assayed their applicability for preclinical
      testing of antiviral compounds. Human immune system (HIS) BLT-NOD/SCID mice were
      inoculated intravenously with a low-passage, clinical isolate of DENV-2, and this
      resulted in sustained viremia and infection of leukocytes in lymphoid and
      nonlymphoid organs. In addition, DENV infection increased serum cytokine levels
      and elicited DENV-2-neutralizing human IgM antibodies. Following restimulation
      with DENV-infected dendritic cells, in vivo-primed T cells became activated and
      acquired effector function. An adenosine nucleoside inhibitor of DENV decreased
      the circulating viral RNA when administered simultaneously or 2 days
      postinfection, simulating a potential treatment protocol for DENV infection in
      humans. In summary, we demonstrate that BLT mice are susceptible to infection
      with clinical DENV isolates, mount virus-specific adaptive immune responses, and
      respond to antiviral drug treatment. Although additional refinements to the model
      are required, BLT mice are a suitable platform to study aspects of DENV infection
      and pathogenesis and for preclinical testing of drug and vaccine candidates.
      IMPORTANCE Infection with dengue virus remains a major medical problem. Progress
      in our understanding of the disease and development of therapeutics has been
      hampered by the scarcity of small animal models. Here, we show that humanized
      mice, i.e., animals engrafted with components of a human immune system, that were
      infected with a patient-derived dengue virus strain developed clinical symptoms
      of the disease and mounted virus-specific immune responses. We further show that
      this mouse model can be used to test preclinically the efficacy of antiviral
      drugs. 

PMID- 24335304
TI  - Enhanced fusion and virion incorporation for HIV-1 subtype C envelope
      glycoproteins with compact V1/V2 domains.
AB  - In infected people, the HIV-1 envelope glycoprotein (Env) constantly evolves to
      escape the immune response while retaining the essential elements needed to
      mediate viral entry into target cells. The extensive genetic variation of Env is
      particularly striking in the V1/V2 hypervariable domains. In this study, we
      investigated the trade-off, in terms of fusion efficiency, for encoding V1/V2
      domains of different lengths. We found that natural variations in V1/V2 length
      exert a profound impact on HIV-1 entry. Variants encoding compact V1/V2 domains
      mediated fusion with higher efficiencies than related Envs encoding longer V1/V2
      domains. By exchanging the V1/V2 domains between Envs of the same infected person
      or between two persons linked by a transmission event, we further demonstrated
      that V1/V2 domains critically influence both Env incorporation into viral
      particles and fusion to primary CD4 T cells and monocyte-derived dendritic cells.
      Shortening the V1/V2 domains consistently increased Env incorporation and fusion,
      whereas lengthening the V1/V2 domains decreased Env incorporation and fusion.
      Given that in a new host transmitted founder viruses are distinguished by compact
      Envs with fewer glycosylation sites, our study points to fusion and possibly Env
      incorporation into virions as limiting steps for transmission of HIV-1 to a new
      host and suggests that the length and/or the N-glycosylation profile of the V1/V2
      domain influences these early steps in the HIV life cycle. 

PMID- 24335305
TI  - Role of the nuclease activities encoded by herpes simplex virus 1 UL12 in viral
      replication and neurovirulence.
AB  - Enzyme-dead mutations in the herpes simplex virus 1 UL12 gene that abolished its
      endo- and exonuclease activities only slightly reduced viral replication in cell
      cultures. However, the UL12 null mutation significantly reduced viral
      replication, suggesting that a UL12 function(s) unrelated to its nuclease
      activities played a major role in viral replication. In contrast, the enzyme-dead
      mutations significantly reduced viral neurovirulence in mice, suggesting that
      UL12 nuclease activities were critical for viral pathogenesis in vivo. 

PMID- 24335306
TI  - PB2-588I enhances 2009 H1N1 pandemic influenza virus virulence by increasing
      viral replication and exacerbating PB2 inhibition of beta interferon expression.
AB  - The 2009 pandemic H1N1 influenza virus (pdm/09) is typically mildly virulent in
      mice. In a previous study, we identified four novel swine isolates of pdm/09
      viruses that exhibited high lethality in mice. Comparing the consensus sequences
      of the PB2 subunit of human isolates of pdm/09 viruses with those of the four
      swine isolate viruses revealed one consensus mutation: T588I. In this study, we
      determined that 588T is an amino acid mutation conserved in pdm/09 viruses that
      was exceedingly rare in previous human influenza isolates. To investigate whether
      the PB2 with the T5581 mutation (PB2-T558I) has an effect on the increased
      pathogenicity, we rescued a variant containing PB2-588I (Mex_PB2-588I) in the
      pdm/09 virus, A/Mexico/4486/2009(H1N1), referred to as Mex_WT (where WT is wild
      type), and characterized the variant in vitro and in vivo. The results indicated
      that the mutation significantly enhanced polymerase activity in mammalian cells,
      and the variant exhibited increased growth properties and induced significant
      weight loss in a mouse model compared to the wild type. We determined that the
      mutation exacerbated PB2 inhibition of mitochondrial antiviral signaling protein
      (MAVS)-mediated beta interferon (IFN-beta) expression, and PB2-588I was observed
      to bind to MAVS more efficiently than PB2-588T. The variant induced lower levels
      of host IFN-beta expression than the WT strain during infection. These findings
      indicate that the pdm/09 influenza virus has increased pathogenicity upon the
      acquisition of the PB2-T588I mutation and highlight the need for the continued
      surveillance of the genetic variation of molecular markers in influenza viruses
      because of their potential effects on pathogenicity and threats to human health. 

PMID- 24335307
TI  - Aerosolized rift valley fever virus causes fatal encephalitis in african green
      monkeys and common marmosets.
AB  - Rift Valley fever (RVF) is a veterinary and human disease in Africa and the
      Middle East. The causative agent, RVF virus (RVFV), can be naturally transmitted
      by mosquito, direct contact, or aerosol. We sought to develop a nonhuman primate
      (NHP) model of severe RVF in humans to better understand the pathogenesis of RVF
      and to use for evaluation of medical countermeasures. NHP from four different
      species were exposed to aerosols containing RVFV. Both cynomolgus and rhesus
      macaques developed mild fevers after inhalation of RVFV, but no other clinical
      signs were noted and no macaque succumbed to RVFV infection. In contrast, both
      marmosets and African green monkeys (AGM) proved susceptible to aerosolized RVF
      virus. Fever onset was earlier with the marmosets and had a biphasic pattern
      similar to what has been reported in humans. Beginning around day 8 to day 10
      postexposure, clinical signs consistent with encephalitis were noted in both AGM
      and marmosets; animals of both species succumbed between days 9 and 11
      postexposure. Marmosets were susceptible to lower doses of RVFV than AGM.
      Histological examination confirmed viral meningoencephalitis in both species.
      Hematological analyses indicated a drop in platelet counts in both AGM and
      marmosets suggestive of thrombosis, as well as leukocytosis that consisted mostly
      of granulocytes. Both AGM and marmosets would serve as useful models of aerosol
      infection with RVFV. 

PMID- 24335308
TI  - A novel DDB2-ATM feedback loop regulates human cytomegalovirus replication.
AB  - Human cytomegalovirus (HCMV) genome replication requires host DNA damage
      responses (DDRs) and raises the possibility that DNA repair pathways may
      influence viral replication. We report here that a nucleotide excision repair
      (NER)-associated-factor is required for efficient HCMV DNA replication. Mutations
      in genes encoding NER factors are associated with xeroderma pigmentosum (XP). One
      of the XP complementation groups, XPE, involves mutation in ddb2, which encodes
      DNA damage binding protein 2 (DDB2). Infectious progeny virus production was
      reduced by >2 logs in XPE fibroblasts compared to levels in normal fibroblasts.
      The levels of immediate early (IE) (IE2), early (E) (pp65), and early/late (E/L)
      (gB55) proteins were decreased in XPE cells. These replication defects were
      rescued by infection with a retrovirus expressing DDB2 cDNA. Similar patterns of
      reduced viral gene expression and progeny virus production were also observed in
      normal fibroblasts that were depleted for DDB2 by RNA interference (RNAi). Mature
      replication compartments (RCs) were nearly absent in XPE cells, and there were
      1.5- to 2.0-log reductions in viral DNA loads in infected XPE cells relative to
      those in normal fibroblasts. The expression of viral genes (UL122, UL44, UL54,
      UL55, and UL84) affected by DDB2 status was also sensitive to a viral DNA
      replication inhibitor, phosphonoacetic acid (PAA), suggesting that DDB2 affects
      gene expression upstream of or events associated with the initiation of DNA
      replication. Finally, a novel, infection-associated feedback loop between DDB2
      and ataxia telangiectasia mutated (ATM) was observed in infected cells. Together,
      these results demonstrate that DDB2 and a DDB2-ATM feedback loop influence HCMV
      replication. 

PMID- 24335309
TI  - Unraveling the entry mechanism of baculoviruses and its evolutionary
      implications.
AB  - The entry of baculovirus budded virus into host cells is mediated by two distinct
      types of envelope fusion proteins (EFPs), GP64 and F protein. Phylogenetic
      analysis suggested that F proteins were ancestral baculovirus EFPs, whereas GP64
      was acquired by progenitor group I alphabaculovirus more recently and may have
      stimulated the formation of the group I lineage. This study was designed to
      experimentally recapitulate a possible major step in the evolution of
      baculoviruses. We demonstrated that the infectivity of an F-null group II
      alphabaculovirus (Helicoverpa armigera nucleopolyhedrovirus [HearNPV]) can be
      functionally rescued by coinsertion of GP64 along with the nonfusogenic F(def)
      (furin site mutated HaF) from HearNPV. Interestingly, HearNPV enters cells by
      endocytosis and, less efficiently, by direct membrane fusion at low pH. However,
      this recombinant HearNPV coexpressing F(def) and GP64 mimicked group I virus not
      only in its EFP composition but also in its abilities to enter host cells via low
      pH-triggered direct fusion pathway. Neutralization assays indicated that the
      nonfusogenic F proteins contribute mainly to binding to susceptible cells, while
      GP64 contributes to fusion. Coinsertion of GP64 with an F-like protein (Ac23)
      from group I virus led to efficient rescue of an F-null group II virus. In
      summary, these recombinant viruses and their entry modes are considered to
      resemble an evolutionary event of the acquisition of GP64 by an ancestral group I
      virus and subsequent adaptive inactivation of the original F protein. The study
      described here provides the first experimental evidence to support the hypothesis
      of the evolution of baculovirus EFPs. 

PMID- 24335310
TI  - Primary macrophages rely on histone deacetylase 1 and 2 expression to induce type
      I interferon in response to gammaherpesvirus infection.
AB  - Type I interferon is induced shortly following viral infection and represents a
      first line of host defense against a majority of viral pathogens. Not
      surprisingly, both replication and latency of gammaherpesviruses, ubiquitous
      cancer-associated pathogens, are attenuated by type I interferon, although the
      mechanism of attenuation remains poorly characterized. Gammaherpesviruses also
      target histone deacetylases (HDACs), a family of pleiotropic enzymes that modify
      gene expression and several cell signaling pathways. Specifically, we have
      previously shown that a conserved gammaherpesvirus protein kinase interacts with
      HDAC1 and -2 to promote gammaherpesvirus replication in primary macrophages. In
      the current study, we have used genetic approaches to show that expression of
      HDAC1 and -2 is critical for induction of a type I interferon response following
      gammaherpesvirus infection of primary macrophages. Specifically, expression of
      HDAC1 and -2 was required for phosphorylation of interferon regulatory factor 3
      (IRF3) and accumulation of IRF3 at the beta interferon promoter in
      gammaherpesvirus-infected primary macrophages. To our knowledge, this is the
      first demonstration of a specific role for HDAC1 and -2 in the induction of type
      I interferon responses in primary immune cells following virus infection.
      Furthermore, because HDAC1 and -2 are overexpressed in several types of cancer,
      our findings illuminate potential side effects of HDAC1- and -2-specific
      inhibitors that are currently under development as cancer therapy agents.
      IMPORTANCE Gammaherpesviruses establish chronic infection in a majority of the
      adult population and are associated with several malignancies. Infected cells
      counteract gammaherpesvirus infection via innate immune signaling mediated
      primarily through type I interferon. The induction of type I interferon
      expression proceeds through several stages using molecular mechanisms that are
      still incompletely characterized. In this study, we show that expression of HDAC1
      and -2 by macrophages is required to mount a type I interferon response to
      incoming gammaherpesvirus. The involvement of HDAC1 and -2 in the type I
      interferon response highlights the pleiotropic roles of these enzymes in cellular
      signaling. Interestingly, HDAC1 and -2 are deregulated in cancer and are
      attractive targets of new cancer therapies. Due to the ubiquitous and chronic
      nature of gammaherpesvirus infection, the role of HDAC1 and -2 in the induction
      of type I interferon responses should be considered during the clinical
      development of HDAC1- and -2-specific inhibitors. 

PMID- 24335312
TI  - Specific nucleoprotein residues affect influenza virus morphology.
AB  - Influenza virus strains are often pleiomorphic, a characteristic that is largely
      attributed to specific residues in matrix protein 1 (M1). Although the mechanism
      by which M1 controls virion morphology has not yet been defined, it is suggested
      that the M1 interaction with other viral proteins plays an important role. In
      this study, we rescued recombinant virus WSN-AichiM1 containing the spherical
      A/WSN/33 (WSN) backbone and the M1 protein from A/Aichi/2/68 (Aichi). Aichi M1
      differs from WSN M1 by 7 amino acids but includes those identified to be
      responsible for filamentous virion formation. Interestingly, Aichi virus produced
      spherical virions, while WSN-AichiM1 exhibited a long filamentous morphology, as
      detected by immunofluorescence and electron microscopy. Additional incorporation
      of Aichi nucleoprotein (NP) but not the hemagglutinin (HA), neuraminidase (NA),
      or M2 gene to WSN-AichiM1 abrogated filamentous virion formation, suggesting that
      specific M1-NP interactions affect virion morphology. Further characterization of
      viruses containing WSN/Aichi chimeric NPs identified residues 214, 217, and 253
      of Aichi NP as necessary and sufficient for the formation of spherical virions.
      NP residues 214 and 217 localize at the minor groove between the two opposite
      polarity NP helical strands of viral ribonucleocapsids, and residue 253 also
      localizes near the surface of the groove. These findings indicate that NP plays a
      critical role in influenza virus morphology, possibly through its interaction
      with the M1 layer during virus budding. 

PMID- 24335311
TI  - STAT1 interaction with E3-14.7K in monocytes affects the efficacy of oncolytic
      adenovirus.
AB  - Oncolytic viruses based on adenovirus type 5 (Ad5) have been developed as a new
      class of therapeutic agents for cancers that are resistant to conventional
      therapies. Clinical experience shows that these agents are safe, but virotherapy
      alone has not achieved long-term cure in cancer patients. The vast majority of
      oncolytic adenoviruses used in clinical trials to date have deletion of the E3B
      genes. It has been demonstrated that the antitumor potency of the E3B-deleted
      mutant (dl309) is inferior to adenovirus with E3B genes intact. Tumors treated
      with dl309 show markedly greater macrophage infiltration than E3B-intact
      adenovirus. However, the functional mechanisms for this were not previously
      known. Here, we demonstrate that deletion of E3B genes increases production of
      chemokines by monocytes after adenovirus infection and increases monocyte
      migration. The E3B 14,700-Da protein (E3B-14.7K) inhibits STAT1 function by
      preventing its phosphorylation and nuclear translocation. The STAT1 inhibitor,
      fludarabine, rescues the effect of E3B-14.7K deletion by downregulating target
      chemokine expression in human and murine monocytes and results in an enhanced
      antitumor efficacy with dl309 in vivo. These findings have important implications
      for clinical use of E3B-deleted oncolytic adenovirus and other E3B-deleted
      adenovirus vector-based therapy. 

PMID- 24335313
TI  - Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting
      transcription factor AP-1.
AB  - Chronic hepatitis B virus (HBV) infection is a major risk factor for liver
      cirrhosis and hepatocellular carcinoma. Nevertheless, the molecular mechanism of
      HBV replication remains elusive. SIRT1 is a class III histone deacetylase that is
      a structure component of the HBV cccDNA minichromosome. In this study, we found
      by using microarray-based gene expression profiling analysis that SIRT1 was
      upregulated in HBV-expressing cells. Gene silencing of SIRT1 significantly
      inhibited HBV DNA replicative intermediates, 3.5-kb mRNA, and core protein
      levels. In contrast, the overexpression of SIRT1 augmented HBV replication.
      Furthermore, SIRT1 enhanced the activity of HBV core promoter by targeting
      transcription factor AP-1. The c-Jun subunit of AP-1 was bound to the HBV core
      promoter region, as demonstrated by using a chromatin immunoprecipitation assay.
      Mutation of AP-1 binding site or knockdown of AP-1 abolished the effect of SIRT1
      on HBV replication. Finally, SIRT1 inhibitor sirtinol also suppressed the HBV DNA
      replicative intermediate, as well as 3.5-kb mRNA. Our study identified a novel
      host factor, SIRT1, which may facilitate HBV replication in hepatocytes. These
      data suggest a rationale for the use of SIRT1 inhibitor in the treatment of HBV
      infection. 

PMID- 24335314
TI  - Cluster M mycobacteriophages Bongo, PegLeg, and Rey with unusually large
      repertoires of tRNA isotypes.
AB  - Genomic analysis of a large set of phages infecting the common host Mycobacterium
      smegmatis mc(2)155 shows that they span considerable genetic diversity. There are
      more than 20 distinct types that lack nucleotide similarity with each other, and
      there is considerable diversity within most of the groups. Three newly isolated
      temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group
      (cluster M), with the closely related phages Bongo and PegLeg forming subcluster
      M1 and the more distantly related Rey forming subcluster M2. The cluster M
      mycobacteriophages have siphoviral morphologies with unusually long tails, are
      homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit
      a variety of features not previously described in other mycobacteriophages,
      including noncanonical genome architectures and several unusual sets of conserved
      repeated sequences suggesting novel regulatory systems for both transcription and
      translation. In addition to containing transfer-messenger RNA and RtcB-like RNA
      ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or
      nearly complete sets of isotypes. We predict that these tRNAs are used in late
      lytic growth, likely compensating for the degradation or inadequacy of host
      tRNAs. They may represent a complete set of tRNAs necessary for late lytic
      growth, especially when taken together with the apparent lack of codons in the
      same late genes that correspond to tRNAs that the genomes of the phages do not
      obviously encode. IMPORTANCE: The bacteriophage population is vast, dynamic, and
      old and plays a central role in bacterial pathogenicity. We know surprisingly
      little about the genetic diversity of the phage population, although metagenomic
      and phage genome sequencing indicates that it is great. Probing the depth of
      genetic diversity of phages of a common host, Mycobacterium smegmatis, provides a
      higher resolution of the phage population and how it has evolved. Three new
      phages constituting a new cluster M further expand the diversity of the
      mycobacteriophages and introduce novel features. As such, they provide insights
      into phage genome architecture, virion structure, and gene regulation at the
      transcriptional and translational levels.

PMID- 24335315
TI  - Characterization of human astrovirus cell entry.
AB  - Human astroviruses (HAstV) are a frequent cause of gastroenteritis in young
      children and immunocompromised patients. To understand the early steps of HAstV
      infection in the highly permissive Caco-2 cell line, the binding and entry
      processes of the virus were characterized. The half-time of virus binding to the
      cell surface was about 10 min, while virus decapsidation took around 130 min.
      Drugs affecting clathrin-mediated endocytosis, endosome acidification, and actin
      filament polymerization, as well as those that reduce the presence of cholesterol
      in the cell membrane, decreased the infectivity of the virus. The infection was
      also reduced by silencing the expression of the clathrin heavy chain (CHC) by RNA
      interference or by overexpression of dominant-negative mutants of dynamin 2 and
      Eps15. Furthermore, the entry of HAstV apparently depends on the maturation of
      endosomes, since the infection was reduced by silencing the expression of Rab7, a
      small GTPase involved in the early- to late-endosome maturation. Altogether, our
      results suggest that HAstV enters Caco-2 cells using a clathrin-dependent pathway
      and reaches late endosomes to enter cells. Here, we have characterized the
      mechanism used by human astroviruses, important agents of gastroenteritis in
      children, to gain entry into their host cells. Using a combination of biochemical
      and genetic tools, we found that these viruses enter Caco-2 cells using a
      clathrin-dependent endocytic pathway, where they most likely need to travel to
      late endosomes to reach the cytoplasm and begin their replication cycle. 

PMID- 24335316
TI  - Structural basis for HIV-1 neutralization by 2F5-like antibodies m66 and m66.6.
AB  - Antibodies m66.6 and 2F5 are the only effective human HIV-1-neutralizing
      antibodies reported thus far to recognize the N-terminal region of the membrane
      proximal external region (MPER) of the gp41 subunit of the HIV-1 envelope
      glycoprotein. Although 2F5 has been extensively characterized, much less is known
      about antibody m66.6 or antibody m66, a closely related light-chain variant.
      Here, we report the crystal structure of m66 in complex with its gp41 epitope,
      along with unbound structures of m66 and m66.6. We used mutational and binding
      analyses to decipher antibody elements critical for their recognition of gp41 and
      determined the molecular basis that underlies their neutralization of HIV-1. When
      bound by m66, the N-terminal region of the gp41 MPER adopts a conformation
      comprising a helix, followed by an extended loop. Comparison of gp41-bound m66 to
      unbound m66.6 identified three light-chain residues of m66.6 that were confirmed
      through mutagenesis to underlie the greater breadth of m66.6-mediated virus
      neutralization. Recognition of gp41 by m66 also revealed similarities to antibody
      2F5 both in the conformation of crucial epitope residues as well as in the angle
      of antibody approach. Aromatic residues at the tip of the m66.6 heavy-chain third
      complementarity-determining region, as in the case of 2F5, were determined to be
      critical for virus neutralization in a manner that correlated with antibody
      recognition of the MPER in a lipid context. Antibodies m66, m66.6, and 2F5 thus
      utilize similar mechanistic elements to recognize a common gp41-MPER epitope and
      to neutralize HIV-1. 

PMID- 24335317
TI  - Highly divergent integration profile of adeno-associated virus serotype 5
      revealed by high-throughput sequencing.
AB  - Adeno-associated virus serotype 5 (AAV-5) is a human parvovirus that infects a
      high percentage of the population. It is the most divergent AAV, the DNA sequence
      cleaved by the viral endonuclease is distinct from all other described serotypes
      and, uniquely, AAV-5 does not cross-complement the replication of other
      serotypes. In contrast to the well-characterized integration of AAV-2, no
      published studies have investigated the genomic integration of AAV-5. In this
      study, we analyzed more than 660,000 AAV-5 integration junctions using high
      throughput integrant capture sequencing of infected human cells. The integration
      activity of AAV-5 was 99.7% distinct from AAV-2 and favored intronic sequences.
      Genome-wide integration was highly correlated with viral replication protein
      binding and endonuclease sites, and a 39-bp consensus integration motif was
      revealed that included these features. Algorithmic scanning identified 126 AAV-5
      hot spots, the largest of which encompassed 3.3% of all integration events. The
      unique aspects of AAV-5 integration may provide novel tools for biotechnology and
      gene therapy. IMPORTANCE: Viral integration into the host genome is an important
      aspect of virus host cell biology. Genomic integration studies of the small
      single-stranded AAVs have largely focused on site preferential integration of AAV
      2, which depends on the viral replication protein (Rep). We have now established
      the first genome wide integration profile of the highly divergent AAV-5 serotype.
      Using integrant capture sequencing, more than 600,000 AAV-5 integration junctions
      in human cells were analyzed. AAV-5 integration hot spots were 99.7% distinct
      from AAV-2. Integration favored intronic sequences, occurred on all chromosomes,
      and integration hot spot distribution was correlated with human genomic GAGC
      repeats and transcriptional activity. These features support expansion of AAV-5
      based vectors for gene transfer considerations.

PMID- 24335318
TI  - State Hospitals as "the most integrated setting according to their needs".

PMID- 24335319
TI  - Abolition of the insanity defense violates due process.
AB  - This article, which is based on and expands on an amicus brief the authors
      submitted to the United States Supreme Court, first provides the moral argument
      in favor of the insanity defense. It considers and rejects the most important
      moral counterargument and suggests that jurisdictions have considerable leeway in
      deciding what test best meets their legal and moral policies. The article then
      discusses why the two primary alternatives to the insanity defense, the negation
      of mens rea and considering mental disorder at sentencing, are insufficient to
      achieve the goal of responding justly to severely mentally disordered offenders.
      The last section considers and rejects standard practical arguments in favor of
      abolishing the insanity defense. 

PMID- 24335320
TI  - Commentary: the insanity defense and youths in juvenile court.
AB  - Juveniles, like adults, should be afforded the right to raise an insanity
      defense. In this commentary on the article by Morse and Bonnie on the abolition
      of the insanity defense, we explain why so few juveniles across the United States
      are granted access to the insanity defense and the reasons that they should have
      that option. We also consider whether the Delling case was the best suited
      vehicle to argue for extending constitutional protection to the insanity defense
      nationwide. 

PMID- 24335321
TI  - Challenges for Canada in meeting the needs of persons with serious mental illness
      in prison.
AB  - The number of prison inmates is predicted to rise in Canada, as is concern about
      those among them with mental illness. This article is a selective literature
      review of the epidemiology of serious mental illness (SMI) in prisons and how
      people with SMI respond to imprisonment. We review the required service
      components with a particular focus on care models for people with SMI in the
      Canadian correctional system. An estimated 15 to 20 percent of prison inmates
      have SMI, and this proportion may be increasing. The rate of incarceration of
      aboriginal people is rising. Although treatment in prison is effective, it is
      often unavailable or refused. Many of those with SMI are lost to follow-up within
      months of re-entering the community. There is much policy and service development
      aimed at improving services in Canada. However, the multijurisdictional
      organization of health care and the heterogeneity of the SMI population
      complicate these developments. 

PMID- 24335322
TI  - Commentary: bridging the gaps for former inmates with serious mental illness.
AB  - Serious mental illness is a prominent and vexing problem within the correctional
      systems of North America. Simpson and colleagues draw attention to the
      epidemiology, special characteristics, and management problems relevant to
      Canadian inmates with serious mental illness. Of great interest to those in the
      forensic psychiatric field is the matter of continuation of care for mentally ill
      prisoners, in that untreated or undertreated psychiatric problems are strongly
      associated with poor social functioning and criminal recidivism. In this
      commentary, we expand on the discussion in Simpson et al. of the effectiveness of
      assertive community treatment teams for those former inmates at greatest risk for
      future involvement with the criminal justice system. We also propose outpatient
      civil commitment as one strategy to facilitate the successful return of select
      inmate patients to the community. 

PMID- 24335323
TI  - Commentary: mentally disordered offenders in prison--old problems that still
      require solutions.
AB  - We commend Simpson et al. for addressing an important topic: the care and
      treatment of prisoners with serious mental illness. We welcome the authors'
      conclusions, but we identify some problems that can often frustrate attempts to
      improve services to this group. 

PMID- 24335324
TI  - Characteristics of female homicide offenders found not guilty by reason of
      insanity.
AB  - Until recently, there has been little information regarding female offenders who
      commit homicides that are motivated by psychosis. We investigated gender
      differences in the characteristics of psychosis and crime variables in
      psychotically motivated homicide. In the study, conducted at a large U.S.
      forensic facility, we reviewed the records of women (n = 47) found not guilty by
      reason of insanity (NGRI) who were hospitalized between January 1991 and August
      2005 for a homicide offense. A random sample of 47 men who were committed during
      the same period for the same offenses was selected for comparison. Religious
      delusions were found more often in women who killed infants (0-1 year of age) and
      children between the ages of 2 and 18. Women were more likely to have a diagnosis
      of an affective problem and borderline personality disorder. The results indicate
      gender-specific areas to focus on during clinical and forensic assessments of the
      risk of violence in women with psychosis. 

PMID- 24335325
TI  - Commentary: women, violence, and insanity.
AB  - There is less research about homicidal women than about their male counterparts.
      Women are often considered the gentler sex, and their risk of perpetrating
      violent acts is underestimated. In attempts to understand violence by women with
      mental illness, female homicide offenders found not guilty by reason of insanity
      (NGRI) are an important subpopulation. Understanding common factors in this
      subpopulation (such as psychosis with religious delusions) may help in preventing
      severe violence perpetrated by women with mental illness. However, as with other
      crimes, those with mental illness who commit homicide may often have rational,
      nonpsychotic motives (such as anger, jealousy, self-defense, money, or criminal
      intent) and would not be captured in a study of those found NGRI. Further,
      caution must be used when studying an NGRI population, as there are potential
      gender biases in findings of insanity. 

PMID- 24335326
TI  - Commentary: delusions and homicide in women--stories, old and new.
AB  - It is not possible to predict homicide in an actuarial or statistical sense with
      any appreciable degree of accuracy. In an important and interesting study,
      Ferranti and colleagues highlight the centrality of religious delusions in women
      who kill children, consistent with the long-standing recognition that delusions
      are especially important in the context of violence by the mentally ill. They
      also note, among other findings, high rates of borderline personality disorder
      among female homicide offenders found not guilty by reason of insanity (60%)
      compared with their male counterparts (9%). As a result, the combination of
      religious delusions, unstable affect, access to children, and features of
      borderline personality disorder can usefully guide clinical decision-makers
      toward higher levels of treatment and follow-up, especially in women with
      aggressive tendencies. Despite the importance of this kind of risk stratification
      and treatment, however, homicide remains impossible to predict at an individual
      level. 

PMID- 24335327
TI  - Scylla and Charybdis: dual roles and undetected risks in campus mental health
      assessments.
AB  - Recent high-profile events involving the mental health of students and the
      subsequent impact on the campus community have focused attention on the need for
      quality mental health care and informed risk assessment on college campuses. When
      on-campus clinicians are asked to provide direct clinical care to students and to
      perform objective evaluations of at-risk students at the request of university
      administrators, there is a potential for multiple role conflict. Campus
      clinicians may find themselves involved in maintaining a difficult balance
      between student and university interests. We describe some of the problems that
      arise in balancing decisions between the two, with a specific emphasis on threats
      to confidentiality and informed consent, dual role conflicts, and the limits of
      clinical expertise. 

PMID- 24335328
TI  - Love, spirituality, and regret: thematic analysis of last statements from death
      row, Texas (2006-2011).
AB  - Individuals awaiting execution have high rates of mental illness and
      psychological problems. We examined themes and psychological factors in last
      statements before execution in Texas between December 2006 and July 2011 (n = 79)
      and compared them to our previous research on last statements between April 2002
      and November 2006 (n = 100). We used the Thematic Guide for Suicide Prediction to
      examine the state of mind of the prisoners facing imminent death. The most common
      themes in last statements were love (82%), spirituality (52%), and regret (39%).
      The most common psychological factors were indirect expressions (43%),
      identification-egression (i.e., identification with a lost or rejecting person or
      with any lost ideal) (40%), rejection-aggression (38%), and unbearable
      psychological pain (37%). These features were constant over time. Evidence of
      deteriorating mental health, unbearable psychological pain, and increased suicide
      risk suggests an ethics-related medical duty for psychiatrists to object to the
      death sentence. 

PMID- 24335329
TI  - Transgendered and incarcerated: a review of the literature, current policies and
      laws, and ethics.
AB  - Being transgendered, described as feeling that one is of the opposite gender, can
      be a difficult experience in today's culture. Those who are transgendered and
      incarcerated experience much more stress. There is a significant population of
      transgendered individuals in today's prison system, with estimates suggesting
      that the number is higher proportionally than in the general population. The
      question of how to treat these individuals while maintaining the safety and
      security of the institutions remains unanswered. In this article, we review the
      epidemiology of transgendered individuals in the general population and
      correctional facilities, describe current guidelines for the standard of care,
      and discuss how various correctional systems in this country apply them. We will
      also review case law with respect to the management and treatment of
      transgendered incarcerated individuals. Finally, we discuss the challenges
      involved in serving this population, such as provision of safe housing and
      medically necessary treatment. This review is provided to help in educating the
      forensic expert on current questions and potential future directions in the
      management of this population. 

PMID- 24335330
TI  - The Oregon Psychiatric Security Review Board: 1978-2012.
AB  - This commentary describes the functioning of the Oregon Psychiatric Security
      Review Board (PSRB) from 1978 through 2011, when the Oregon Legislature altered
      the authority of the PSRB in regard to certain hospitalized insanity acquittees.
      Following the Hinckley verdict, the American Psychiatric Association recognized
      the PSRB as a possible future model for the management and treatment of insanity
      acquittees. The commentary provides an overview of the board from administrative
      and empirical viewpoints over this 34-year period and discusses the changes made
      in PSRB statutes in 2012 and the implication of these changes for the future
      management of insanity acquittees in Oregon. 

PMID- 24335331
TI  - How can forensic systems improve justice for victims of offenders found not
      criminally responsible?
AB  - Controversy has arisen surrounding findings of not criminally responsible (NCR)
      or not guilty by reason of insanity (NGRI) in recent years. In some countries,
      the debate has been driven by the concerns of victims, who are seeking greater
      information on discharge, accountability on the part of the offender, and
      involvement in the disposition of NCR or NGRI perpetrators. Their demands raise
      questions about proportionality between the seriousness of the index offense and
      the disposition imposed, the place of retribution in the NCR regimen, and the
      ethics-related challenges that emerge from this tension. We conducted a
      literature review focused on the relationship of victims to NCR and NGRI
      processes. The literature is limited. However, theoretical reasoning suggests
      that interventions based on restorative justice principles reduce persistently
      negative feelings and increase a sense of justice for victims of criminally
      responsible defendants. Opportunities and problems with extending such processes
      into the area of mentally abnormal offenders are discussed. 

PMID- 24335332
TI  - Secondary complex chromosome rearrangement identified by chromosome analysis and
      FISH subsequent to detection of an unbalanced derivative chromosome 12 by SNP
      array analysis.
AB  - Microarray analysis is used to detect small copy number changes (deletions and
      duplications) that may be associated with genetic syndromes and phenotypic
      abnormalities. However, there are limitations to what microarrays are able to
      detect. We present a patient referred for microarray in whom chromosome analysis
      identified a more complex structural rearrangement than was indicated by the
      microarray. Our studies included Affymetrix Cytoscan HD array, chromosome
      analysis and fluorescence in situ hybridization (FISH) using a subtelomere probe
      targeting chromosome 3. Array analysis revealed a 6.45-Mb terminal duplication of
      3q28q29 and a 1.02-Mb terminal deletion of 12p13.33. This suggested an unbalanced
      translocation derivative. In order to investigate visibility of the
      rearrangement, chromosome analysis was performed, revealing an additional
      balanced complex chromosome rearrangement involving chromosomes 3 and 11,
      including a translocation with breakpoints at 3p13 and 11p11.2, as well as a
      paracentric inversion of segment 3p25p13 translocated onto chromosome 11.
      Subtelomere FISH confirmed that the duplicated chromosome 3q material observed in
      the array analysis was localized to distal 12p. This case clearly illustrates the
      combined utilization of classic cytogenetics, FISH and array technologies to
      better characterize chromosomal abnormalities.

PMID- 24335335
TI  - Hodgkin lymphoma and hypothermia: case report and review of the literature.
AB  - We report the development of hypothermia in a patient with Hodgkin lymphoma which
      resolved with chemotherapy administration. A review of the literature revealed 16
      previous reports of hypothermia in patients with Hodgkin lymphoma. Overall
      prognosis seems to be unfavorable. To the best of our knowledge this is the first
      report of hypothermia in a patient with Hodgkin lymphoma transforming from
      chronic lymphocytic leukemia (Richter's syndrome). A possible pathophysiology
      could be paraneoplastic autonomic neuropathy. Physicians should be aware that
      Hodgkin lymphoma can present with hypothermia and should carefully monitor newly
      diagnosed patients with advanced disease for this complication. Likewise,
      patients with Hodgkin lymphoma who develop hypothermia should be screened for
      signs of autonomic neuropathy.

PMID- 24335333
TI  - ARABIDOPSIS THALIANA HOMEOBOX25 uncovers a role for Gibberellins in seed
      longevity.
AB  - Seed longevity is crucial for agriculture and plant genetic diversity, but it is
      limited by cellular damage during storage. Seeds are protected against aging by
      cellular defenses and by structures such as the seed coat. We have screened an
      activation-tagging mutant collection of Arabidopsis (Arabidopsis thaliana) and
      selected four dominant mutants with improved seed longevity (isl1-1D to isl4-1D)
      under both natural and accelerated aging conditions. In the isl1-1D mutant,
      characterized in this work, overexpression of the transcription factor
      ARABIDOPSIS THALIANA HOMEOBOX25 (ATHB25; At5g65410) increases the expression of
      GIBBERELLIC ACID3-OXIDASE2, encoding a gibberellin (GA) biosynthetic enzyme, and
      the levels of GA1 and GA4 are higher (3.2- and 1.4-fold, respectively) in the
      mutant than in the wild type. The morphological and seed longevity phenotypes of
      the athb25-1D mutant were recapitulated in transgenic plants with moderate (4- to
      6-fold) overexpression of ATHB25. Simultaneous knockdown of ATHB25, ATHB22, and
      ATHB31 expression decreases seed longevity, as does loss of ATHB25 and ATHB22
      function in a double mutant line. Seeds from wild-type plants treated with GA and
      from a quintuple DELLA mutant (with constitutive GA signaling) are more tolerant
      to aging, providing additional evidence for a role of GA in seed longevity. A
      correlation was observed in several genotypes between seed longevity and mucilage
      formation at the seed surface, suggesting that GA may act by reinforcing the seed
      coat. This mechanism was supported by the observation of a maternal effect in
      reciprocal crosses between the wild type and the athb25-1D mutant. 

PMID- 24335334
TI  - Both PHYTOCHROME RAPIDLY REGULATED1 (PAR1) and PAR2 promote seedling
      photomorphogenesis in multiple light signaling pathways.
AB  - Arabidopsis (Arabidopsis thaliana) seedlings undergo photomorphogenesis in the
      light and etiolation in the dark. Light-activated photoreceptors transduce the
      light signals through a series of photomorphogenesis promoting or repressing
      factors to modulate many developmental processes in plants, such as
      photomorphogenesis and shade avoidance. CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) is
      a conserved RING finger E3 ubiquitin ligase, which mediates degradation of
      several photomorphogenesis promoting factors, including ELONGATED HYPOCOTYL5
      (HY5) and LONG HYPOCOTYL IN FAR-RED1 (HFR1), through a 26S proteasome-dependent
      pathway. PHYTOCHROME RAPIDLY REGULATED1 (PAR1) was first detected as an early
      repressed gene in both phytochrome A (phyA)-mediated far-red and phyB-mediated
      red signaling pathways, and subsequent studies showed that both PAR1 and PAR2 are
      negative factors of shade avoidance in Arabidopsis. However, the role of PAR1 and
      PAR2 in seedling deetiolation, and their relationships with other
      photomorphogenesis promoting and repressing factors are largely unknown. Here, we
      confirmed that both PAR1 and PAR2 redundantly enhance seedling deetiolation in
      multiple photoreceptor signaling pathways. Their transcript abundances are
      repressed by phyA, phyB, and cryptochrome1 under far-red, red, and blue light
      conditions, respectively. Both PAR1 and PAR2 act downstream of COP1, and COP1
      mediates the degradation of PAR1 and PAR2 through the 26S proteasome pathway.
      Both PAR1 and PAR2 act in a separate pathway from HY5 and HFR1 under different
      light conditions, except for sharing in the same pathway with HFR1 under far-red
      light. Together, our results substantiate that PAR1 and PAR2 are positive factors
      functioning in multiple photoreceptor signaling pathways during seedling
      deetiolation. 

PMID- 24335336
TI  - Penetration studies of an extremely lipophilic active model substance from an oil
      in-water emulsion: influence of the lipophilicity of the formulation in human
      skin - part 2.
AB  - The effect of the lipophilicity of a carrier on human skin penetration of an
      extremely lipophilic active model substance was evaluated by using Franz type
      diffusion cells. Oil-in-water model emulsions containing different amounts of the
      oily phase were prepared, and Myritol(r) PC (M-PC) was selected as lipophilic
      marker component of the oily phase. The penetrated amounts of the lipophilic
      model substance salicyloyl phytosphingosine (SP) were determined by high
      performance liquid chromatography with ultraviolet detection, while M-PC was
      detected using gas chromatography coupled with mass spectrometry. It has been
      ascertained that the amount of the lipid phase within the emulsion influenced the
      penetration profile of the active ingredient SP. The emulsion containing the
      lowest proportion of the lipid phase provides the best conditions for SP
      penetration. Surprisingly, the penetration behavior of M-PC was influenced by the
      oily phase in the same way. Regarding the M-PC and the SP penetration profiles
      from each emulsion, a solvent drag mechanism can be assumed whereby M-PC acts as
      penetration enhancer. In conclusion, the penetration rate of the active
      ingredient SP and the marker component M-PC are in reverse proportion to the oil
      content of the formulations. The lipophilicity of SP and M-PC, their solubility
      and their thermodynamic activity within the vehicle could have an effect on their
      penetration behavior. Additionally, M-PC has the property to enhance the
      penetration rates of extremely lipophilic substances even at low concentrations.

PMID- 24335337
TI  - Zoledronic acid induces a significant decrease of circulating endothelial cells
      and circulating endothelial precursor cells in the early prostate cancer
      neoadjuvant setting.
AB  - PURPOSE: Published data demonstrated that zoledronic acid (ZOL) exhibits
      antiangiogenetic effects. A promising tool for monitoring antiangiogenic
      therapies is the measurement of circulating endothelial cells (CECs) and
      circulating endothelial precursor cells (CEPs) in the peripheral blood of
      patients. Our aim was to investigate the effects of ZOL on levels of CECs and
      CEPs in localized prostate cancer. METHODS: Ten consecutive patients with a
      histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and
      received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56
      days (T56). Blood samples were collected at the following times: T0 (before the
      first infusion of ZOL), T3 (72 h after the first dose), T28, T56 (both just
      before the ZOL infusion) and T84 (28 days after the last infusion of ZOL) and
      CEC/CEP levels were directly quantified by flow cytometry at all these time
      points. RESULTS: Our analyses highlighted a significant reduction of mean
      percentage of CECs and CEPs after initiation of ZOL treatment [p = 0.014 (at day
      3) and p = 0.012 (at day 84), respectively]. CONCLUSION: These preliminary
      results demonstrate that ZOL could exert an antiangiogenic effect in early
      prostate cancer through CEP and CEC modulation.

PMID- 24335338
TI  - Cigarette trafficking in five northeastern US cities.
AB  - BACKGROUND: Cigarette taxation is effective in reducing tobacco use in the USA.
      However, these benefits are reduced when taxes are unpaid. Cigarette trafficking
      (ie, the illegal importation of cigarettes into a high-tax jurisdiction from a
      lower-tax jurisdiction) is well documented in high-tax places like New York City
      (NYC), but the extent of trafficking in other northeastern cities is relatively
      unknown. OBJECTIVE: To estimate the extent of cigarette trafficking in Boston,
      NYC, Philadelphia, Providence and Washington, DC, and project the benefits of
      reducing cigarette trafficking for recouping lost taxes and reducing smoking in
      these cities. METHODS: Littered cigarette packs were collected from a random
      sample of Census tracts in five US cities. Data collection yielded 1439 total
      littered packs. The share of cigarette packs bearing proper local, known non
      local, foreign or unknown, or no tax stamp was calculated for each city. These
      data were used to estimate tax revenue recovery if cigarette trafficking could be
      eliminated. We also estimated the extent to which eliminating cigarette
      trafficking would reduce cigarette consumption. RESULTS: Overall, 58.7% of packs
      did not have a proper local tax stamp, and 30.5-42.1% were attributed to
      trafficking. We estimate that eliminating cigarette trafficking would result in
      declines in youth smoking prevalence ranging from negligible in low-tax cities
      like Philadelphia to up to 9.3% in higher-tax NYC. We estimate that these five
      cities could recoup $680-729 million annually in cigarette tax revenue if
      cigarette trafficking was eliminated. CONCLUSIONS: Reducing cigarette trafficking
      would increase the effectiveness of tobacco taxes in reducing smoking and
      generate additional tax revenue, particularly in higher-taxed cities. Federal
      action to reduce cigarette trafficking, such as a track-and-trace system, is
      needed.

PMID- 24335339
TI  - Towards a greater understanding of the illicit tobacco trade in Europe: a review
      of the PMI funded 'Project Star' report.
AB  - BACKGROUND: Following a legal agreement with the European Union (EU), Philip
      Morris International (PMI) commissions a yearly report ('Project Star', PS) on
      the European illicit cigarette trade from KPMG, the global accountancy firm.
      METHODS: Review of PS 2010 report. Comparison with data from independent sources
      including a 2010 pan-European survey (N=18,056). FINDINGS: Within PS, data
      covering all 27 EU countries are entered into a model. While the model itself
      seems appropriate, concerns are identified with the methodologies underlying the
      data inputs and thus their quality: there is little transparency over
      methodologies; interview data underestimate legal non-domestic product partly by
      failing to account for legal cross-border sales; illicit cigarette estimates rely
      on tobacco industry empty pack surveys which may overestimate illicit; and there
      is an over-reliance on data supplied by PMI with inadequate external validation.
      Thus, PMI sales data are validated using PMI smoking prevalence estimates, yet
      PMI is unable to provide sales (shipment) data for the Greek islands and its
      prevalence estimates differ grossly from independent data. Consequently,
      comparisons with independent data suggest PS will tend to overestimate illicit
      cigarette levels particularly where cross-border shopping is frequent (Austria,
      Finland, France) and in Western compared with Eastern European countries. The
      model also provides data on the nature of the illicit cigarette market
      independent of seizure data suggesting that almost a quarter of the illicit
      cigarette market in 2010 comprised PMI's own brands compared with just 5%
      counterfeited PMI brands; a finding hidden in PMI's public representation of the
      data. CONCLUSIONS: PS overestimates illicit cigarette levels in some European
      countries and suggests PMI's supply chain control is inadequate. Its publication
      serves the interests of PMI over those of the EU and its member states. PS
      requires greater transparency, external scrutiny and use of independent data.

PMID- 24335340
TI  - Evidences that estrogen receptor alpha interferes with adiponectin effects on
      breast cancer cell growth.
AB  - Adiponectin, the most abundant protein secreted by adipose tissue, exhibits
      insulin-sensitizing, anti-inflammatory, antiatherogenic, and antiproliferative
      properties. In addition, it appears to play an important role also in the
      development and progression of several obesity-related malignancies, including
      breast cancer.   Here, we demonstrated that adiponectin induces a dichotomic
      effect on breast cancer growth. Indeed, it stimulates growth in ERalpha+ MCF-7
      cells while inhibiting proliferation of ERalpha- MDA-MB-231 cells. Notably, only
      in MCF-7 cells adiponectin exposure exerts a rapid activation of MAPK
      phosphorylation, which is markedly reduced when knockdown of the ERalpha gene
      occurred. In addition, adiponectin induces rapid IGF-IR phosphorylation in MCF-7
      cells, and the use of ERalpha siRNA prevents this effect. Moreover, MAPK
      activation induced by adiponectin was reversed by IGF-IR siRNA.
      Coimmunoprecipitation studies show the existence of a multiprotein complex
      involving AdipoR1, APPL1, ERalpha, IGF-IR, and c-Src that is responsible for MAPK
      signaling activation in ERalpha+ positive breast cancer cells. It is well known
      that in addition to the rapid effects through non-genomic mechanisms, ERalpha
      also mediates nuclear genomic actions. In this concern, we demonstrated that
      adiponectin is able to transactivate ERalpha in MCF-7 cells. We showed the
      classical features of ERalpha transactivation: nuclear localization,
      downregulation of mRNA and protein levels, and upregulation of estrogen-dependent
      genes. Thus, our study clarifies the molecular mechanism through which
      adiponectin modulates breast cancer cell growth, providing evidences on the cell
      type dependency of adiponectin action in relationship to ERalpha status. 

PMID- 24335341
TI  - Clinical application of liver stiffness measurement using transient elastography:
      a surgical perspective.
AB  - Liver biopsy (LB) remains the gold standard for assessing the severity of liver
      fibrosis; however, LB is often limited by its invasiveness, sampling error, and
      intra-/inter-observer variability in histological interpretation. Furthermore,
      repeated LB examinations within a short time interval are ineligible in real
      clinical practice. Thus, due to the pressing need for non-invasive surrogates,
      over the past decade, significant progress has been made in non-invasively
      assessing liver fibrosis. Of the methods now available, transient elastography
      (TE) appears to be an excellent tool for assessing liver fibrosis and also has
      some prognostic value in surgical settings. Recent studies have proposed the
      extended role of TE in the surgical field, based on the concept that TE values
      show significant correlations with portal hypertension and hepatocellular
      carcinoma development. TE appears promising in predicting postoperative short
      term outcomes such as hepatic insufficiency or complications and long-term
      outcomes such as recurrence or liver-related death. Furthermore, TE may be useful
      in predicting the severity of liver fibrosis progression due to recurrence of
      hepatitis C virus infection or other underlying liver diseases after
      transplantation. TE cannot completely replace other tests accompanied with
      hepatic surgical treatments, including LB, endoscopic examination, hepatic venous
      pressure gradient evaluation, or the indocyanine green retention test. However,
      TE represents an important non-invasive tool that enables more efficient and
      tailored management strategies for patients who were treated with liver resection
      or transplantation. This review discusses extended TE applications in the
      surgical setting, such as hepatic resection or transplantation.

PMID- 24335342
TI  - Long non-coding RNAs and chromatin modifiers: their place in the epigenetic code.
AB  - The emergence of long non-coding RNAs (lncRNAs) has shaken up our conception of
      gene expression regulation, as lncRNAs take prominent positions as components of
      cellular networks. Several cellular processes involve lncRNAs, and a significant
      number of them have been shown to function in cooperation with chromatin
      modifying enzymes to promote epigenetic activation or silencing of gene
      expression. Different model mechanisms have been proposed to explain how lncRNAs
      achieve regulation of gene expression by interacting with the epigenetic
      machinery. Here we describe these models in light of the current knowledge of
      lncRNAs, such as Xist and HOTAIR, and discuss recent literature on the role of
      the three-dimensional structure of the genome in the mechanism of action of
      lncRNAs and chromatin modifiers. 

PMID- 24335343
TI  - Presentation of untreated systemic mastocytosis as recurrent, pulseless
      electrical-activity cardiac arrests resistant to cardiac pacemaker.
AB  - Recurrent, pulseless-electrical-activity (PEA) cardiac arrests were the novel
      presentation of untreated systemic mastocytosis in an 85-year-old woman who
      lacked cutaneous findings of mastocytosis. Despite prior implantation of a dual
      chamber cardiac pacemaker 3 weeks previously for similar spells, she experienced
      a PEA arrest accompanied by flushing, increased urinary N-methylhistamine
      excretion and serum tryptase values on the day of presentation to our clinic.
      Bone marrow biopsy findings conducted to rule out breast cancer metastases showed
      30% mast cell infiltration, aberrant expression of CD25 and a positive c-kit
      Asp816Val mutation. Treatment with a combination of H1 and H2 receptor blockers
      reduced flushing and eliminated hypotension. Maintenance medication included
      aspirin, cetirizine, ranitidine, montelukast, oral cromolyn sodium and an
      epinephrine autoinjector (as needed). At 6-month follow-up, the patient remained
      free of PEA arrests, flushing, or any clinical signs of mastocytosis or mast cell
      degranulation. PEA cardiac arrests may therefore be a presenting sign of
      untreated systemic mastocytosis.

PMID- 24335344
TI  - Evaluation of tubulin polymerization and chronic inhibition of proteasome as
      citotoxicity mechanisms in bortezomib-induced peripheral neuropathy.
AB  - Bortezomib (BTZ) is the first proteasome inhibitor entered in clinical practice.
      Peripheral neuropathy is likely to be a class side effect of these drugs,
      although its severity is largely variable, and it deserves to be further
      investigated, since the mechanisms of BTZ-induced peripheral neurotoxicity (BiPN)
      are still unknown.   In our study, we investigated in vivo and in vitro possible
      pathogenic events relevant to BiPN using a well-established rat model, with
      particular reference to the extent of proteasome inhibition and the effects on
      alpha-tubulin polymerization in sciatic nerves and dorsal root ganglia specimens
      obtained from animals treated with chronic regimens at a dose of 0.2 mg/kg
      intravenously. The same assessments were also performed after a single injection.
      Moreover, these studies were replicated in vitro using embryonic DRG neurons
      exposed to 100 nM BTZ and adult DRG neurons exposed to 10-50 nM BTZ for 24 h and
      48 h. A significant increase in the polymerized fraction of alpha-tubulin and
      prolonged proteasome inhibition were observed after the chronic BTZ treatment in
      vivo. Recovery to physiological levels was observed after a 4-week follow-up post
      treatment period. Proteasome inhibition and increased alpha-tubulin
      polymerization were also observed following BTZ treatment of both embryonic and
      adult DRG neurons in vitro. Our in vivo results suggest that proteasome
      inhibition and alteration of tubulin dynamics contribute to BiPN. The in vitro
      systems here described reliably replicate the in vivo results, and might
      therefore be used for further mechanistic studies on the effects of proteasome
      inhibitors on neurons. 

PMID- 24335345
TI  - Geldanamycin-induced phosphatidylserine translocation in the erythrocyte
      membrane.
AB  - BACKGROUND/AIMS: Geldanamycin, a benzoquinone ansamycin antibiotic, and its
      analogues induce apoptosis of tumor cells and are thus considered for the
      treatment of cancer. Similar to apoptosis of nucleated cells, erythrocytes may
      enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage
      and by cell membrane scrambling with phosphatidylserine-exposure at the
      erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca(2+)
      concentration ([Ca(2+)]i) and formation of ceramide. The present study explored,
      whether geldanamycin modifies [Ca(2+)]i, ceramide formation, cell volume and
      phosphatidylserine abundance at the erythrocyte surface. METHODS: Erythrocyte
      volume was estimated from forward scatter, phosphatidylserine-abundance from
      annexin V binding, hemolysis from hemoglobin release, ceramide formation from
      binding of fluorescent antibodies and [Ca(2+)]i from Fluo3-fluorescence. RESULTS:
      A 48 hours exposure to geldanamycin significantly decreased forward scatter (>= 5
      uM), significantly increased annexin-V-binding (>= 25 uM), but did not
      significantly modify Fluo3-fluorescence (up to 50 uM). The annexin-V-binding
      following geldanamycin treatment was not significantly modified by removal of
      extracellular Ca(2+) but was paralleled by significantly increased ceramide
      formation (50 uM). CONCLUSIONS: Geldanamycin stinulated eryptosis, an effect at
      least partially due to ceramide formation.

PMID- 24335346
TI  - Validation of the Revised International Prognostic Scoring System for patients
      with myelodysplastic syndromes.
AB  - The objective of this study is to externally validate the recently published
      Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic
      syndrome (MDS) and compare it with the International Prognostic Scoring System
      (IPSS). We conducted a retrospective study of 173 adult MDS patients who had not
      received disease-altering treatment. Using the Cox hazard method, we found the
      IPSS-R to be a significant predictor of survival (p < 0.001, hazard ratio, HR =
      1.82, 95% confidence interval, CI 1.57-2.12) and time to acute myeloid leukemia
      (AML; p < 0.001, HR = 2.05, 95% CI 1.55-2.70). The IPSS-R has greater prognostic
      power for survival and time to AML compared with the IPSS, given higher Somers' D
      values (0.41 vs. 0.39 and 0.55 vs. 0.53, respectively). Using the log-rank test,
      we found a significant difference when comparing IPSS-R groups (p < 0.02), with
      the exception of the high-risk versus very high-risk group comparison. The IPSS-R
      reclassified low-risk and intermediate-1 IPSS groups into four groups (log-rank,
      p < 0.001) and intermediate-2 and high-risk IPSS groups into three groups (log
      rank, p < 0.04, excluding high-risk vs. very high-risk comparison). We conclude
      that the IPSS-R has significant prognostic utility for MDS patients.

PMID- 24335347
TI  - Parenting stress and child physical health among a low-income sample: The
      moderating role of child anxiety.
AB  - This study examined child anxiety as a potential moderator of the relationship
      between parenting stress and child physical health. Low-income youth (N = 109, M
      = 9.51 years old) and their parents completed measures of anxiety, health-related
      quality of life, and parenting stress in an outpatient clinic. As an objective
      measure of physical health, medical service utilization was extracted from
      medical records. Parenting stress was associated significantly with worse health
      related quality of life and higher service utilization. Child anxiety moderated
      the relationship between stress and health. Health psychologists should target
      both family stress and child anxiety in promoting better health outcomes among
      low-income families. 

PMID- 24335348
TI  - Brief report: Emotional distress and recent stressful life events in long QT
      syndrome mutation carriers.
AB  - To study emotional distress in symptomatic and asymptomatic long QT syndrome
      mutation carriers who had experienced a recent stressful life event. The
      participants were 209 symptomatic and 279 asymptomatic long QT syndrome mutation
      carriers. Emotional distress was assessed with the Cope questionnaire and
      stressful life events with the Social Readjustment Rating Scale. Symptomatic long
      QT syndrome mutation carriers with burdening recent stressful life events
      reported a higher emotional distress (beta = 0.35, p < 0.001), while the
      asymptomatic did not show such difference (beta = 0.13, p = 0.393). Symptomatic
      long QT syndrome mutation carriers who have experienced stressful life events
      recently report an increased emotional distress. 

PMID- 24335349
TI  - Practical problems encountered during the cultivation of an open-source
      reconstructed human epidermis model on a polycarbonate membrane and protein
      quantification.
AB  - During recent years, the importance of in vitro technology in skin research has
      increased significantly. A variety of skin culture models have been developed and
      commercialized. In this respect, the availability of reconstructed human
      epidermis (RHE) equivalents represents a significant improvement compared to the
      use of monolayer cultures. However, when an in-house RHE model is being
      developed, researchers might encounter some difficulties during cultivation. The
      scope of this paper is to report our experiences and practical problems with the
      development of a three-dimensional RHE model cultured on a polycarbonate
      membrane. Some important issues including cell density, the use of lysing
      enzymes, culture media, cell storage and viability, cell confluency and protein
      extraction are reported and optional solutions are given.

PMID- 24335350
TI  - Long-term relations among prosocial-media use, empathy, and prosocial behavior.
AB  - Despite recent growth of research on the effects of prosocial media, processes
      underlying these effects are not well understood. Two studies explored
      theoretically relevant mediators and moderators of the effects of prosocial media
      on helping. Study 1 examined associations among prosocial- and violent-media use,
      empathy, and helping in samples from seven countries. Prosocial-media use was
      positively associated with helping. This effect was mediated by empathy and was
      similar across cultures. Study 2 explored longitudinal relations among prosocial
      video-game use, violent-video-game use, empathy, and helping in a large sample of
      Singaporean children and adolescents measured three times across 2 years. Path
      analyses showed significant longitudinal effects of prosocial- and violent-video
      game use on prosocial behavior through empathy. Latent-growth-curve modeling for
      the 2-year period revealed that change in video-game use significantly affected
      change in helping, and that this relationship was mediated by change in empathy. 

PMID- 24335352
TI  - pACICU2 is a conjugative plasmid of Acinetobacter carrying the aminoglycoside
      resistance transposon TnaphA6.

PMID- 24335351
TI  - EGFR signaling and autophagy dependence for growth, survival, and therapy
      resistance.
AB  - The epidermal growth factor receptor (EGFR) is amplified or mutated in various
      human epithelial tumors. Its expression and activation leads to cell
      proliferation, differentiation, and survival. Consistently, EGFR amplification or
      expression of EGFR variant 3 (EGFRvIII) is associated with resistance to
      conventional cancer therapy through activation of pro-survival signaling and DNA
      repair mechanisms. EGFR targeting has successfully been exploited as strategy to
      increase treatment efficacy. Nevertheless, these targeting strategies have only
      been proven effective in a limited percentage of human tumors. Recent knowledge
      indicates that EGFR deregulated tumors display differences in autophagy and
      dependence on autophagy for growth and survival and the use of autophagy to
      increase resistance to EGFR-targeting drugs. In this review the dependency on
      autophagy and its role in mediating resistance to EGFR-targeting agents will be
      discussed. Considering the current knowledge, autophagy inhibition could provide
      a novel strategy to enhance therapy efficacy in treatment of EGFR deregulated
      tumors.

PMID- 24335354
TI  - Continuation or reintroduction of an antineoplastic strategy after documented
      disease progression.

PMID- 24335355
TI  - Why do aortas cleave or dilate? Clues from an electronic scanning microscopy
      study in human ascending aortas.
AB  - In ascending aorta aneurysms (AscAA) the whole vessel wall dilates, while in
      aortic dissections (AD) the wall cleaves into two sheets. Both may present fine
      elastic fragmentation and a decrease in collagen. We analyzed whether alterations
      in the three-dimensional structure of these fibers could be involved in the
      pathogenesis of AscAA/AD. Specimens obtained at surgery for these diseases (n = 4
      for each) and on coronary artery bypass surgery (controls, n = 4) were submitted
      to treatments which either preserve collagen or the elastic structure. These
      samples were examined by scanning electron microscopy. In all groups most of the
      collagen fibers were packed, forming laminar structures very similar to the
      elastic lamellae. In AscAA/AD, the fibers showed signs of degradation and/or
      fragmentation. Elastic tissue was distributed in large sheets with fenestrations,
      with smaller branches between them. In 1 of the dissection cases and 2 of the
      aneurysm cases elastic sheet fragmentation, which under light microscopy seems to
      be located at random, had a pattern of clefts which were irregular but
      approximately transversal to the main axis of the wall. The recognition of this
      pattern and the degradation/fragmentation of collagen and elastic fibrils
      facilitates understanding of why the wall is weak and affected by aneurysms and
      dissections.

PMID- 24335353
TI  - Proteome and phosphoproteome characterization reveals new response and defense
      mechanisms of Brachypodium distachyon leaves under salt stress.
AB  - Salinity is a major abiotic stress affecting plant growth and development.
      Understanding the molecular mechanisms of salt response and defense in plants
      will help in efforts to improve the salt tolerance of crops. Brachypodium
      distachyon is a new model plant for wheat, barley, and several potential biofuel
      grasses. In the current study, proteome and phosphoproteome changes induced by
      salt stress were the focus. The Bd21 leaves were initially treated with salt in
      concentrations ranging from 80 to 320 mm and then underwent a recovery process
      prior to proteome analysis. A total of 80 differentially expressed protein spots
      corresponding to 60 unique proteins were identified. The sample treated with a
      median salt level of 240 mm and the control were selected for phosphopeptide
      purification using TiO2 microcolumns and LC-MS/MS for phosphoproteome analysis to
      identify the phosphorylation sites and phosphoproteins. A total of 1509
      phosphoproteins and 2839 phosphorylation sites were identified. Among them, 468
      phosphoproteins containing 496 phosphorylation sites demonstrated significant
      changes at the phosphorylation level. Nine phosphorylation motifs were extracted
      from the 496 phosphorylation sites. Of the 60 unique differentially expressed
      proteins, 14 were also identified as phosphoproteins. Many proteins and
      phosphoproteins, as well as potential signal pathways associated with salt
      response and defense, were found, including three 14-3-3s (GF14A, GF14B, and 14-3
      3A) for signal transduction and several ABA signal-associated proteins such as
      ABF2, TRAB1, and SAPK8. Finally, a schematic salt response and defense mechanism
      in B. distachyon was proposed. 

PMID- 24335356
TI  - Lipid-cell cycle nexus: SREBP regulates microRNAs targeting Fbxw7.

PMID- 24335357
TI  - [Cancer statistics in the world].
AB  - With regard to cancer incidence worldwide, stomach and liver cancers are
      representative in Asia and bladder cancer is representative in the United States
      and Europe. In Australia and Sweden, melanoma of the skin is amongst the top 5
      cancers in terms of incidence. Colorectal cancer and breast cancer rank highly in
      all countries studied. However, the incidence of colorectal cancer in Japan has
      been decreasing recently and has not been increasing in other countries, except
      for China. The incidence of breast cancer in the United States and Europe is
      twice as high as it is in Asian countries, and these rates have been increasing
      in all countries. With regard to cancer mortality worldwide, stomach and liver
      cancers are associated with high mortality rates in Asia, as is the case with
      incidence rates. In the United States and Europe, the mortality rate associated
      with ovarian cancer is relatively high. Lung and colorectal cancers rank highly
      in terms of mortality worldwide, and pancreatic cancer is also included in the
      top 5 cancers in all countries, except for China and Brazil. 

PMID- 24335358
TI  - [Oral management for cancer patients].
AB  - Chemotherapy and radiotherapy administered to cancer patients can be harmful
      because of their effect on normal cells as well as cancer cells, and cause many
      adverse events. The oral cavity is one of the sites most vulnerable to the direct
      and indirect effects of cancer therapy. Severe adverse events of the oral cavity
      can not only reduce a patient's QOL, but also disrupt cancer treatment. We
      discuss the concept of oral management by maintenance of the oral environment. 

PMID- 24335360
TI  - [Supporting lymphedema patients by working together among different job
      categories].
AB  - Therapeutic methods and preventive education related to lymphedema are beginning
      to attract attention as a result of revisions to the associated medical treatment
      fees. Currently, fees for guidance on the prevention of lymphedema and the
      payment of medical expenses for compression garments after the onset of
      lymphedema are covered by insurance. However, complex treatments are not covered,
      and the response to the onset of lymphedema differs according to the treatment
      facility. Patients who develop lymphedema have to contend with it for long
      periods of time. In addition, the difference in the response noted between
      facilities delays the start of treatment and hampers continued treatment.
      Multidisciplinary collaboration is essential for patients to continue treatment
      without difficulty and face lymphedema with confidence. This study describes
      multidisciplinary collaboration methods to assist lymphedema patients as well as
      challenges for the future treatment of this disease. 

PMID- 24335361
TI  - [Stoma care in patients with malignant disease].
AB  - The aim of stoma care and rehabilitation is improving the quality of life of the
      patient with a stoma. There are more than 1,700 stoma specialist nurses in Japan,
      eg, enterostomal therapists(ET)and wound, ostomy, and continence nurses(WOCN),
      who are involved in the care of patients with stomas. In this manuscript, we
      describe our role in the care of patients with temporary/permanent stomas created
      for emergency disease and/or palliative care, and the adverse effects of various
      current chemotherapies. 

PMID- 24335362
TI  - [Support of cancer patients by counseling].
AB  - Special counselors of consultation support centers at cancer hospitals have the
      difficult task of providing support to patients and families that receive the
      difficult diagnosis of cancer. Patients and their family first receive a notice
      and an explanation of the conditions of the disease, along with details of the
      standard future treatment policy in that country. Such information may not be
      conveyed by medical experts in a manner in which the patient can understand it,
      and very few patients are able to select a treatment plan on their own. With the
      support of a special counselor, the patient can determine the best way to manage
      the illness, and the counselor supports the decision-making process regarding the
      best treatment option. Moreover, support is offered to help the patient accept
      the diagnosis and maintain a balance of daily activities, which facilitate
      treatment continuation. With the intervention of a special counselor, problems
      that arise can be addressed directly and the counselor can summarize the
      patient's intentions and can act immediately to find solutions. Medical social
      workers understand that the patient is an individual who is concerned and who
      must be convinced and understand the situation in order to judge the situation
      and act accordingly. This approach gives courage to the patient, increases the
      will to live, and helps the patient regain a sense of self. A medical social
      worker's role is to help find answers and to suggest ideas for problem solving,
      to allow for patients to care for themselves and others. 

PMID- 24335363
TI  - [Subset analysis of preoperative lymphocyte ratio in stage II or III colorectal
      cancer patients treated with oral tegafur-uracil and protein-bound polysaccharide
      K].
AB  - PURPOSE: We have reported, in a randomized, controlled study, that tegafur
      uracil(UFT)and protein-bound polysaccharide K(PSK)combination therapy
      significantly improves the 5-year disease-free survival rate and reduces the risk
      of recurrence compared to UFT alone for Stage II or III colorectal cancer. In
      this study, we examined the efficacy of PSK by stratifying patients according to
      the preoperative lymphocyte ratio(Lym). METHODS: In a randomized, controlled
      study, 205 patients were eligible(137 in the UFT/PSK group and 68 in the UFT
      group). Of these, 193 patients with available preoperative Lym data were
      analysed(131 in the UFT/PSK group and 62 in the UFT group). RESULTS: Among
      patients with a preoperative Lym of <35%, the relapse-free survival(RFS)rate was
      76.5% in the UFT/PSK group and 55.8% in the UFT group(p=0.008). However, in
      patients with a preoperative Lym of >=35%, the RFS rate did not differ between
      the 2 groups. Similarly, overall survival was significantly higher in the UFT/PSK
      group than in the UFT group in patients with a preoperative Lym of <35%, whereas
      no intergroup difference was found among patients with a preoperative Lym of
      >=35%. CONCLUSION: This study suggests that a low preoperative Lym is a good
      predictor for response to PSK in patients with Stage II or III colorectal cancer.

PMID- 24335364
TI  - [Outcomes of cetuximab combination chemotherapy in clinical practice for patients
      with metastatic colorectal cancer].
AB  - We aimed to evaluate the reproducibility of cetuximab combination chemotherapy as
      a standard treatment for patients with metastatic colorectal cancer in our
      hospital using actual clinical data. This study included 14, 9, and 4 patients
      who received third-line, second-line, and first-line treatment, respectively. The
      overall response rate(RR), progression-free survival( PFS), and overall
      survival(OS)were calculated according to treatment line and were compared with
      the results of largescale clinical studies. In patients undergoing third-line
      treatment, the RR was 14.3%, while the median PFS and OS were 2.9 and 9.6 months,
      respectively. These results were almost identical to those of the NCIC CTG CO. 17
      study. In patients undergoing second-line treatment, the RR was 22.2% and the
      median PFS and OS were 5.8 and 7.1 months, respectively. These results were not
      inferior to those of the BOND study. In patients undergoing first-line treatment,
      partial response was observed in 75% of patients and stable disease was observed
      in 25% of patients. One patient subsequently underwent surgery. The RR(75%)was
      equal to that observed in the CRYSTAL study and the OPUS study. Standard
      treatment using cetuximab combination chemotherapy was found to be reproducible
      as third-line and second-line treatments in our clinical practice. Few patients
      received first-line treatment; hence, a larger number of patients will have to be
      evaluated in the future. Nevertheless, the administration of cetuximab
      combination chemotherapy may be appropriate as a medical treatment strategy for
      patients with metastatic colorectal cancer. 

PMID- 24335365
TI  - [Assessment of the clinical efficacy and safety of fulvestrant in heavily
      pretreated patients with hormone-receptor positive metastatic breast cancer-a
      single-institution experience].
AB  - Fulvestrant, a pure estrogen receptor antagonist with no known agonist effects,
      was approved in September 2011 for the treatment of hormone-receptor positive
      metastatic breast cancer(MBC)in postmenopausal women in Japan. Here, we present a
      retrospective review of data from 73 heavily pretreated patients who received a
      high-dose regimen of fulvestrant in our hospital. Patients received a median of 3
      endocrine therapies(range: 1-7)prior to the fulvestrant regimen. Partial response
      was observed in 4 patients, and 10 patients experienced stable disease for more
      than 6 months(objective response rate: 5.5%; clinical benefit rate: 19.2%). The
      median time to progression was 2.8 months. Fulvestrant was well tolerated;
      however, Grade 3 neuropathy at the injection site was observed in 2 patients. Of
      12 patients, 3 responded to endocrine therapy following fulvestrant treatment.
      Our clinical experience indicates that fulvestrant can be administered to
      patients pretreated with several lines of endocrine therapy, although its
      efficacy as first- or second-line endocrine therapy has been demonstrated in
      clinical trial settings. 

PMID- 24335366
TI  - [Safety and efficacy of pegylated liposomal Doxorubicin and Carboplatin on
      platinum-sensitive recurrent epithelial ovarian cancer].
AB  - OBJECTIVE: We evaluated the safety and efficacy of pegylated liposomal
      doxorubicin(PLD)and carboplatin(CBDCA)(CD) for platinum-sensitive recurrent
      epithelial ovarian cancer. METHODS: From December 2010 to June 2011, 9 eligible
      patients with histologically confirmed, recurrent epithelial ovarian cancer,
      which was deemed platinum-sensitive, were enrolled onto the study.
      PLD(30mg/m2)and CBDCA(area under the curve[AUC]5)were administered intravenously
      on day 1 of the cycle. The chemotherapy regimen was repeated every 4 weeks, until
      disease progression or completion of 6 cycles. RESULTS: A total of 49 treatment
      cycles of CD were administered to 9 patients. The median platinum-free interval
      was 18.3 months. Patients with Grade 3/4 hematological toxicities were observed
      to have leucopenia(11.1%), neutropenia(44.4%), anemia (22.2%), and
      thrombocytopenia (22.2%). No Grade 3/4 non-hematological toxicities were
      observed, and no treatment related death occurred. Seven patients(77.7%)responded
      to CD(4 complete responses and 3 partial responses). The median progression-free
      survival and overall survival times were 15.1 and 23.7 months. CONCLUSION: CD
      treatment seems to be a safe and effective chemotherapy regimen for platinum
      sensitive recurrent epithelial ovarian cancer.

PMID- 24335367
TI  - [Short-term safety evaluation of trastuzumab administrated intravenously over 30
      minutes with 100 mL saline solution with a focus on infusion reaction].
AB  - In 2011, trastuzumab was approved via public knowledge-based application for
      administration over 30 minutes from the second round if the first infusion is
      well tolerated. However, cardiovascular strain and the trastuzumab-specific side
      effect of infusion reaction induced by an increase in the infusion rate on
      administering trastuzumab with 250 mL saline over 30 minutes need to be
      considered. To address these concerns, we evaluated trastuzumab administration
      with a reduced volume of 100 mL saline over 30 minutes. This method was well
      tolerated without an increase in the frequency of infusion reaction on
      retrospective comparison of the 2 administration methods. Thus, administration of
      trastuzumab with 100 mL of saline over 30 minutes considerably reduces infusion
      time, benefiting both patients and healthcare providers. 

PMID- 24335368
TI  - [An assessment tool for chemotherapy-induced nausea and vomiting and intervention
      outcomes].
AB  - Chemotherapy-induced nausea and vomiting(CINV)is the most unpleasant side effect
      for patients receiving cancer chemotherapy. Moderately emetic anticancer drugs
      show a wide range of emetic frequencies, and the use or nonuse of antiemetics is
      optionally described without specifics. In the present study, we clarified the
      state of CINV presentation caused by moderately emetic anticancer drugs using the
      MASCC Antiemesis Tool, a nausea-and-vomiting evaluation tool developed by the
      Multinational Association of Supportive Care in Cancer(MASCC)for patients with
      colorectal cancer. Of the 32 subjects, 5 (15.6%)had vomiting and
      22(68.8%)experienced nausea. The timing of their occurrence and their nausea
      scores were accurately and easily clarified. This study's findings suggested that
      the current regimens need to be reviewed, particularly because all patients
      exhibited late nausea; therefore, we modified our antiemetic regimens through the
      Cancer Chemotherapy Regimen Review Board of this hospital. After the modification
      was introduced, significant improvement was seen in the control of both acute and
      late nausea/vomiting. 

PMID- 24335369
TI  - [Postoperative adjuvant chemotherapy for gastric cancer after the adjuvant
      chemotherapy trial of S-1 for gastric cancer in Hiroshima prefecture: results
      from a questionnaire survey and future challenges].
AB  - A questionnaire survey on postoperative adjuvant chemotherapy for gastric cancer
      was conducted for 76 hospitals affiliated with the Hiroshima Oncology Group of
      Gastric Cancer in Hiroshima prefecture in January 2011. Responses were obtained
      from 29 hospitals, including 12 core cancer treatment hospitals, and the
      following results were obtained. The percentage of patients completing 1 year of
      oral S-1 was >70%, affecting approximately 75% of the entire hospital cohort.
      Dose reduction was conducted in approximately 30% of patients because of age,
      poor PS, and renal insufficiency. The standard S-1 regimen (4 weeks of S-1
      treatment followed by 2 weeks of rest)was adopted in almost half of the patients,
      whereas the rest of the patients received another treatment schedule such as 2
      weeks of treatment followed by 1 week of rest. Dose reduction and withdrawal of S
      1 due to adverse events were conducted more frequently in hospitals with low
      completion rates of 1-year S- 1 treatment than those with a high completion rate.
      S-1 was most commonly discontinued because of subjective adverse events and
      patient request, although the discontinuation rate according to objective adverse
      events such as bone marrow depression was not very high. The fact that some
      hospitals had high completion rates suggested the importance of supplementary
      tools for patient IC. 

PMID- 24335370
TI  - [A case of postoperative thymic carcinoma recurrence that was effectively treated
      with combination chemotherapy of nedaplatin and docetaxel].
AB  - We report a case of postoperative recurrence of thymic carcinoma that was
      effectively treated with combination chemotherapy of nedaplatin(NDP)and
      docetaxel(DOC). We performed thymectomy for thymoma in a 55-year-old man. The
      pathological diagnosis was squamous cell thymic carcinoma(pT3N0M0, Stage III).
      The patient was observed without postoperative radiotherapy being administered.
      Six months after the operation, the patient was admitted to our department with
      carcinomatous pericarditis. Whole-body examination revealed multiple lung and
      liver metastases and a left femoral metastasis. After pericardiocentesis,
      radiation therapy was administered for the left femoral metastasis. Combination
      chemotherapy (NDP[60mg/m2]/DOC[70mg/m2])was administered for the multiple lung
      and liver metastases. After 4 cycles of chemotherapy, the multiple lung
      metastases were completely resolved and the liver metastases were clearly
      reduced. Partial response and acceptable toxicity were identified. Thymic
      carcinoma is a rare epithelial neoplasm for which the optimal chemotherapy
      regimen has not yet been established. Combination chemotherapy with NDP/DOC was
      effective in the case of our patient with postoperative thymic squamous cell
      carcinoma recurrence, and it can be considered as a promising regimen for
      patients from the standpoint of clinical efficacy. 

PMID- 24335371
TI  - [An elderly patient with advanced breast cancer who responded to treatment with
      letrozole-a case report].
AB  - An 85-year-old woman was diagnosed as having cancer of the left breast at another
      hospital in August 2008. As she was judged to be an unsuitable candidate for
      surgery and had dementia; therefore, she was followed-up without treatment. When
      the patient visited our hospital in March 2010, a hemorrhagic mass lesion, 5 cm
      in diameter, was observed in the left breast. We investigated the possibility of
      metastases and found that the tumor had infiltrated the chest wall, with
      metastases to the axillary and intrathoracic lymph nodes. Therefore, advanced
      breast cancer with left-sided pleural effusion and metastases to the pleura and
      bone was diagnosed. A needle biopsy revealed that the tumor was a ductal
      carcinoma, which was estrogen receptor(ER)positive, progesterone
      receptor(PgR)positive, and human epidermal growth factor receptor 2(HER2) (1+).
      Despite the presence of distant metastases, the patient's systemic condition was
      reasonably good. Therefore, she was judged to be suitable for some form of
      treatment, and treatment with letrozole was initiated. Six months after the start
      of treatment, the primary lesion decreased in size and pleural effusion
      disappeared. Three years later, the existing lesions have not increased in size
      and no new lesion has appeared. Endocrine therapy may be effective for the
      treatment of advanced hormone-sensitive cancers in elderly patients. 

PMID- 24335372
TI  - [A case of estrogen receptor-positive metastatic breast cancer in a
      postmenopausal woman treated with ethinyl estradiol].
AB  - The patient was 77-year-old woman whose breast cancer had metastasized to the
      bone and soft tissue 5 years after surgery. Although she had been sequentially
      treated with endocrine therapies following chemotherapies, new metastatic lesions
      in the pleura and skin appeared 8 years after recurrence. The biopsied skin
      tissue showed high positivity for estrogen receptor(ER), was negative for human
      epidermal growth factor receptor 2(HER2), and had a low Ki-67 labeling index.
      Following the treatment with exemestane(EXE)for 3 months, ethinyl
      estradiol(EE2)was administered at 3mg/day. After 4 months of treatment, the lymph
      nodes shrunk to 35% of their size and pleural effusion disappeared. The efficacy
      of EE2 was observed for 10 months. Subsequently, fulvestrant was administered
      because the skin lesions showed progressive disease. Adverse events such as
      nausea and general fatigue were observed at the beginning of EE2 therapy.
      Pigmentation of the nipple and areola and cystic swelling of the cervical canal
      were observed after a few months. This therapy can be considered to be effective
      in patients with ER-positive metastatic breast cancer who have been heavily
      treated with endocrine therapies and chemotherapies.

PMID- 24335373
TI  - [A case of imatinib-resistant gastrointestinal stromal tumor treated with low
      dose sunitinib].
AB  - The patient was an 82-year-old man who had undergone resection of a
      gastrointestinal stromal tumor(GIST)of the small intestine in January 2000, when
      he was 69 years old. As peritoneal recurrences were diagnosed in June 2002, we
      performed peritoneal tumorectomy twice, and the perirectal tumor was controlled
      with imatinib for over 7 years. Resistance to imatinib was diagnosed in March
      2011, and treatment was switched to sunitinib. Administration of sunitinib was
      started at 50mg/day for 28 days followed by treatment withdrawal for 14 days;
      however, the dose needed to be reduced twice and then discontinued owing to the
      occurrence of side effects and pemphigoid. During discontinuation of sunitinib,
      the tumor increased in size and cancer pain appeared; therefore, sunitinib was re
      administered at a very low-dose of 12.5mg every alternate day. Low dose sunitinib
      was effective; the perirectal tumor was reduced and cancer pain disappeared.

PMID- 24335374
TI  - [A case report of recurrent small bowel adenocarcinoma successfully treated with
      monoclonal antibody against EGFR and S-1].
AB  - A man in 30s was admitted to our hospital with a complaint of abdominal and back
      pain. Abdominal CT scan showed a large mass and double balloon endoscopy detected
      a tumor of the jejunum. The pathological diagnosis of biopsy samples was poorly
      differentiated adenocarcinoma. After radical resection, adjuvant chemotherapy
      with mFOLFOX6 was administered, however, a recurrent lesion developed. Although
      the lesion was successfully removed again, it did not react to the combination
      therapy with irinotecan and cisplatin. Because the tumor showed a high percentage
      of epidermal growth factor receptor (EGFR) expression and also had a wild-type
      KRAS status, a therapeutic strategy targeting EGFR was selected. The patient
      started on panitumumab associated with S-1 and obtained a complete response on CT
      6 weeks later. Small bowel adenocarcinoma is an aggressive malignancy with a poor
      prognosis and little information about its definitive chemotherapy. Analysis of
      molecular characterization, an increase in reported experience, and prospective
      trials are needed to improve a prognosis. 

PMID- 24335375
TI  - [A case of metastatic colorectal cancer with hyperammonemic encephalopathy
      induced by 5-FU in a patient continuously treated with XELOX therapy].
AB  - We report a rare case of a patient with metastatic colorectal cancer who
      experienced hyperammonemic encephalopathy induced by 5 -fluorouracil(5-FU)and was
      continuously treated with capecitabine plus oxaliplatin(XELOX)therapy. A 60 years
      man with anorexia and weight loss was diagnosed with Stage IV rectal cancer, and
      chemotherapy with XELOX was initiated. When the second course of XELOX therapy
      was administered, the patient found it difficult to take oral capecitabine.
      Subsequently, modified FOLFOX6 was administered. Complications such as nausea and
      vomiting were observed on day 2, with confusion and cognitive disturbances on day
      3 . Laboratory examination revealed hyperammonemia, and therefore, branched-chain
      amino acid solutions were administered as treatment. The patient's symptoms
      disappeared entirely on day 4. He is currently receiving XELOX therapy.

PMID- 24335376
TI  - [A case of local recurrence of rectal carcinoma 10 years after initial surgery].
AB  - Here, we report an extremely rare case of local recurrence of rectal cancer 10
      years after initial tumor resection. A 53-year-old man underwent abdominoperineal
      resection for advanced rectal cancer at a local hospital. The tumor was graded as
      pStage II (pA, pN0, pH0, pP0, pM0, curA)as per the Japanese Classification of
      Colorectal Carcinoma, seventh edition, and diagnosed as a moderately
      differentiated adenocarcinoma on histopathological examination. Subsequently, the
      patient received adjuvant chemotherapy for 5 years. Although the patient lived
      without any recurrences after adjuvant chemotherapy, unfortunately, blood
      examination showed a high carcinoembryonic antigen(CEA)level 10 years after the
      initial surgical treatment. Computed tomography(CT)and positron emission
      tomography(PET)/CT revealed a perineal tumor, 40mm in size, without other distant
      metastases. On diagnosis of local recurrence of rectal cancer, the patient
      underwent surgical tumor resection at Okayama University Hospital. The tumor was
      determined to be a well- to moderately differentiated adenocarcinoma by
      histopathological examination, suggesting local recurrence of the primary rectal
      adenocarcinoma. Moreover, the radial margin was free of cancer. The patient is
      now doing well without any re-recurrence 30 months after the second surgical
      treatment, without any adjuvant chemotherapy. 

PMID- 24335377
TI  - [Primary diffuse large B-cell lymphoma of the uterine cervix successfully treated
      with rituximabplus cyclophosphamide, doxorubicin, vincristine, and prednisone
      chemotherapy-a case report].
AB  - Primary malignant lymphoma of the uterine cervix is a rare disease, and the
      therapeutic strategy has not been clearly established. A 45-year old woman
      presented with vaginal bleeding and hypermenorrhea in January 2012. Physical
      examination revealed a mass in the pelvic cavity approximately the size of a
      neonate's head. Pelvic magnetic resonance imaging(MRI) showed a solid mass 11 cm
      in size in the uterine cervix with homogeneous low intensity on T1-weighted
      images, iso-high intensity on T2-weighted images, and heterogeneous iso-high
      intensity on gadolinium-diethylenetriaminepentaacetate(Gd- DTPA)-enhanced images.
      Multiple lymphadenopathy were also detected in the pelvis. The Papanicolaou smear
      indicated class 5 cervical cytology, and a subsequent histological examination by
      a punch biopsy of the cervix showed diffuse infiltration of medium- to large
      sized mononuclear cells that stained positive for CD20 and CD79a and negative for
      CD3, CD5, and EBER. Bone marrow biopsy revealed no abnormality. Positron emission
      tomography-computed tomography(PET-CT)showed strong
      fluorodeoxyglucose(FDG)accumulation in the uterine cervix mass, and in the pelvic
      and right inguinal lymphadenopathy. The patient was diagnosed with diffuse large
      B-cell lymphoma of the uterine cervix, Ann Arbor stage II AE. She was
      successfully treated with 8 courses of rituximab plus cyclophosphamide,
      doxorubicin, vincristine, and prednisone(R-CHOP) chemotherapy, and maintains a
      complete remission. 

PMID- 24335378
TI  - [A case in which chromosome 5q deletion syndrome resistant to lenalidomide
      therapy transformed to refractory anemia with excess blasts].
AB  - An 80-year-old man was admitted to our hospital because of pancytopenia. Bone
      marrow examination revealed an increase in the number of dysplastic cells
      indicating trilineage dysplasia. A 5q13q31 deletion was the only genetic
      abnormality found, and consequently, 5q deletion syndrome was diagnosed. Although
      lenalidomide therapy was initiated, it had to be discontinued because of Stevens
      Johnson syndrome, which occurred during the second course of treatment. There was
      no discernible hematological improvement, and bone marrow aspiration showed
      transformation to refractory anemia with excess blasts-2(RAEB-2)after
      lenalidomide therapy. However, by changing the therapy to azacitidine,
      cytogenetic remission was achieved. 

PMID- 24335379
TI  - Increased metabolic stress in Zucker diabetic fatty rat kidney and pancreas.
AB  - BACKGROUND/AIMS: Obesity and diabetes (hereafter termed diabesity) are among the
      most challenging global health problems. Since the main pathophysiological
      complications in diabesity are hyperglycemia, hyperlipidemia, insulin resistance,
      cardiomyopathy, nephropathy, and urinary infections, the kidney and pancreas are
      the potential target organs affected in the above conditions. However, the
      precise molecular mechanisms of disease progression and complications are still
      unclear. The Zucker homozygous (FA/FA) diabetic fatty (ZDF) rat is a genetic
      model for obesity and type 2 diabetes. Our previous studies, using cardiac
      muscles have demonstrated metabolic and oxidative stress in ZDF rats. In the
      present study, our aim was to investigate oxidative stress associated metabolic
      complications in ZDF rat kidney and pancreas. METHODS: Here we have measured
      oxidative stress, glutathione (GSH)-dependent metabolism and mitochondrial
      respiratory functions in the kidney and pancreas of ZDF and Zucker lean (ZL,
      +/FA) control rats. RESULTS: Our results showed an increase in reactive oxygen
      species, NO production, lipid and protein peroxidation in ZDF rat kidney and
      pancreas accompanied by alterations in GSH-dependent metabolism and mitochondrial
      function. Western blot analysis has also confirmed increased expression of
      oxidative stress marker proteins in ZDF rats. CONCLUSION: We have demonstrated
      that ZDF rats develop metabolic complications associated with oxidative stress
      and mitochondrial dysfunction. Thus, these results might have implications in
      understanding the etiology and pathology of diabesity.

PMID- 24335381
TI  - Does community-wide chronic kidney disease management improve patient outcomes?
AB  - BACKGROUND: The number of patients starting renal replacement therapy (RRT) is
      increasing in England, as it is worldwide. Improvements in the management of
      chronic kidney disease (CKD) across communities to alter this trend are a public
      health priority. We have prospectively studied changes in the incidence and
      modality of treatment for end-stage renal disease following the introduction of a
      CKD management programme in the West Midlands region of England. METHODS:
      Nephrology service to approximately 700 000 adult population of mixed ethnicity
      in urban and suburban areas, many with social deprivation. The programme was
      introduced in stages between 2003 and 2006 and comprised primary care education
      and financial incentives, personal clinical reports written directly to patients
      following every consultation, routine laboratory estimated glomerular filtration
      rate (eGFR) reporting, eGFR graph surveillance to identify and monitor patients
      at risk, multidisciplinary pre-RRT care and conservative care. Prevalent
      patients: 10 552 with CKD and 8509 without CKD with diabetes. OUTCOMES: access to
      nephrology care, trends in RRT incidence and starting modality, place of death
      without RRT. Incident count was adjusted for changes in the local adult
      population recorded in national censuses. RESULTS: Ninety-one per cent of
      patients aged >=75 years with incident CKD stage 5 were known to a nephrologist.
      The population-adjusted incident RRT rate peaked in 2005 and then declined; the
      proportion starting with transplant, peritoneal dialysis or haemodialysis by
      arterio-venous fistula increased to 63% by 2012 (P = 0.001 versus 2005). Fifty
      two per cent of patients receiving planned conservative care without dialysis
      died out of hospital. CONCLUSIONS: Following the introduction of a community-wide
      systematic CKD management programme, the population-adjusted incidence of RRT
      reduced, modality of initiation of RRT improved and a majority of patients
      receiving planned conservative care without dialysis died out of hospital.

PMID- 24335380
TI  - Prevalence and correlates of fatigue in chronic kidney disease and end-stage
      renal disease: are sleep disorders a key to understanding fatigue?
AB  - BACKGROUND: Fatigue is an important symptom to patients with advanced chronic
      kidney disease (CKD). The aim of this study is to examine the prevalence and
      severity of fatigue among non-dialysis-dependent CKD and end-stage renal disease
      (ESRD) patients, to examine the association of fatigue with subjective and
      objective sleep quality, and to identify other modifiable factors associated with
      fatigue. METHODS: A cross-sectional survey of 87 non-dialysis-dependent CKD (eGFR
      <=45 ml/min/1.73 m(2)) and 86 ESRD patients was done using the Functional
      Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) and 36-Item Short-Form
      (SF-36) vitality scale. Higher FACIT-F score denoted less fatigue. Objective
      sleep was assessed using in-home polysomnography. Predictors of fatigue were
      determined using a linear regression model. RESULTS: The mean FACIT-F score among
      all participants was 34.5 +/- 11.0. Mean scores were similar among CKD and ESRD
      groups (34.25 +/- 11.28 vs. 34.73 +/- 10.86; p = 0.73). On univariate analyses,
      patients with higher levels of fatigue were more likely to have cardiovascular
      disease, benzodiazepine use, depressive symptoms, and slightly lower hemoglobin
      and serum albumin levels. There was no significant association between severity
      of sleep apnea and level of fatigue (Apnea Hypopnea Index 20.1 +/- 27.6 vs. 20.3
      +/- 22.0; p = 0.69). Presence of cardiovascular disease, low serum albumin,
      depressive symptoms, poor subjective sleep quality, excessive daytime sleepiness
      and restless legs syndrome were independently associated with greater fatigue in
      multivariable regression models. The FACIT-F score correlated closely with the SF
      36 vitality score (r = 0.81, p < 0.0001). CONCLUSIONS: Patients with advanced CKD
      and ESRD experience profound fatigue. Depressive symptoms, restless legs
      syndrome, excessive daytime sleepiness, and low albumin levels may provide
      targets for interventions to improve fatigue in patients with advanced CKD.

PMID- 24335382
TI  - Ischaemia-reperfusion injury: a major protagonist in kidney transplantation.
AB  - Ischaemia-reperfusion injury (IRI) is a frequent event in kidney transplantation,
      particularly when the kidney comes from a deceased donor. The brain death is
      usually associated with generalized ischaemia due to a hyperactivity of the
      sympathetic system. In spite of this, most donors have profound hypotension and
      require administration of vasoconstrictor agents. Warm ischaemia after kidney
      vessels clamping and the cold ischaemia after refrigeration also reduce oxygen
      and nutrients supply to tissues. The reperfusion further aggravates the state of
      oxidation and inflammation created by ischaemia. IRI first attacks endothelial
      cells and tubular epithelial cells. The lesions may be so severe that they lead
      to acute kidney injury (AKI) and delayed graft function (DGF), which can impair
      the graft survival. The unfavourable impact of DGF is worse when DGF is
      associated with acute rejection. Another consequence of IRI is the activation of
      the innate immunity. Danger signals released by dying cells alarm Toll-like
      receptors that, through adapter molecules and a chain of kinases, transmit the
      signal to transcription factors which encode the genes regulating inflammatory
      cells and mediators. In the inflammatory environment, dendritic cells (DCs)
      intercept the antigen, migrate to lymph nodes and present the antigen to
      immunocompetent cells, so activating the adaptive immunity and favouring
      rejection. Attempts to prevent IRI include optimal management of donor and
      recipient. Calcium-channel blockers, l-arginine and N-acetylcysteine could obtain
      a small reduction in the incidence of post-transplant DGF. Fenoldopam, Atrial
      Natriuretic Peptide, Brain Natriuretic Peptide and Dopamine proved to be helpful
      in reducing the risk of AKI in experimental models, but there is no controlled
      evidence that these agents may be of benefit in preventing DGF in kidney
      transplant recipients. Other antioxidants have been successfully used in
      experimental models of AKI but only a few studies of poor quality have been made
      in clinical transplantation with a few of these agents and we still lack of
      unambiguous demonstration that pre-treatment with these antioxidants can
      attenuate the impact of IRI in kidney transplantation. Interference with the
      signals leading to activation of innate immunity, inactivation of complement or
      manipulation of DCs is a promising therapeutic option for the near future. 

PMID- 24335383
TI  - Re: "Mendelian randomization and estimation of treatment efficacy for chronic
      diseases".

PMID- 24335384
TI  - Racial differences in gout incidence in a population-based cohort:
      Atherosclerosis Risk in Communities Study.
AB  - We examined racial differences in gout incidence among black and white
      participants in a longitudinal, population-based cohort and tested whether racial
      differences were explained by higher levels of serum urate. The Atherosclerosis
      Risk in Communities Study is a prospective, US population-based cohort study of
      middle-aged adults enrolled between 1987 and 1989 with ongoing annual follow-up
      through 2012. We estimated the adjusted hazard ratios and 95% confidence
      intervals of incident gout by race among 11,963 men and women using adjusted Cox
      proportional hazards models. The cohort was 23.6% black. The incidence rate of
      gout was 8.4 per 10,000 person-years (15.5/10,000 person-years for black men,
      12.0/10,000 person-years for black women, 9.4/10,000 person-years for white men,
      and 5.0/10,000 person-years for white women; P < 0.001). Black participants had
      an increased risk of incident gout (for women, adjusted hazard ratio (HR) = 1.69,
      95% confidence interval (CI): 1.29, 2.22; for men, adjusted HR = 1.92, 95% CI:
      1.44, 2.56). Upon further adjustment for uric acid levels, there was modest
      attenuation of the association of race with incident gout (for women, adjusted HR
      = 1.62, 95% CI: 1.24, 2.22; for men, adjusted HR = 1.49, 95% CI: 1.11, 2.00)
      compared with white participants. In this US population-based cohort, black women
      and black men were at increased risk of developing gout during middle and older
      ages compared with whites, which appears, particularly in men, to be partly
      related to higher urate levels in middle-aged blacks. 

PMID- 24335385
TI  - Nocturnal home hemodialysis associates with improvement of electrocardiographic
      features linked to sudden cardiac death.
AB  - Sudden cardiac death (SCD) remains the leading cause of death in hemodialysis
      patients. We performed a retrospective electrocardiograph (ECG) and chart review
      to determine whether hemodialysis modality, frequency, or duration could predict
      change in ECG parameters associated with SCD. Frequent nocturnal hemodialysis was
      associated with an improvement in Tpeak to Tend within 365 days (83.8-71.8 ms, p
      = 0.005) and past 365 days of dialysis initiation (85.9-77.1 ms, p = 0.005) and
      improvement in QRS amplitude variation within 365 days (0.0583-0.0297, p = 0.025)
      and past 365 days of dialysis initiation (0.0546-0.0332, p = 0.029). Compared
      with intermittent conventional hemodialysis, more frequent nocturnal (15/25 vs.
      3/14, p = 0.04) and intermittent nocturnal hemodialysis (INHD) (6/8 vs. 3/14, p =
      0.03) patients decreased Tpeak to Tend. More short-hours daily than INHD patients
      increased T-wave amplitude variation (16/25 vs. 1/8, p = 0.02). These
      improvements occurred before changes in Cornell or Sokolow-Lyon
      electrocardiographic left ventricular mass. Thus, it appears that hemodialysis
      modalities of longer duration are associated with improvements in
      electrocardiographic parameters associated with SCD. Prospective trials are
      required to determine whether dialysis prescription reduces SCD, cardiovascular
      morbidity, and mortality in hemodialysis patients. 

PMID- 24335386
TI  - Left ventricular assist device pump thrombosis: is there a role for glycoprotein
      IIb/IIIa inhibitors?
AB  - Left ventricular assist devices (LVADs) fill a critical need by providing
      circulatory support to patients with end-stage heart failure who are either
      ineligible for heart transplant or too ill to stably wait for an eventual donor
      organ. Furthermore, they are critical to the arsenal of the heart failure
      cardiologist, given the supply/demand mismatch for donor organs. Unfortunately,
      these devices present their own complications. Despite antiplatelet agents and
      systemic anticoagulation, a number of patients present with pump thrombosis, a
      life-threatening event requiring either pump exchange or treatment with systemic
      thrombolytics. In an effort to avoid these morbid therapies, glycogen IIb/IIIa
      inhibitors, which have both antiplatelet and thrombolytic properties, have been
      proposed to treat pump thrombosis. We report here the largest case series using
      these agents and document a previously unreported high failure rate with this
      therapy. 

PMID- 24335387
TI  - Hemodynamics and flow characteristics of a new dialysis port.
AB  - Renal replacement therapy by hemodialysis requires a permanent vascular access.
      Implantable ports offer a potential alternative to standard vascular access
      strategies although their development is limited both in number and extent. We
      explored the fluid dynamics within two new percutaneous bone-anchored dialysis
      port prototypes, both by in vitro experiments and computer simulation. The new
      port is to be fixed to bone and allows the connection of a dialysis machine to a
      central venous catheter via a built-in valve. We found that the pressure drop
      induced by the two ports was between 20 and 50 mmHg at 500 ml/min, which is
      comparable with commercial catheter connectors (15-80 mmHg). We observed the
      formation of vortices in both geometries, and a shear rate in the physiological
      range (<10,000s-1), which is lower than maximal shear rates reported in
      commercial catheters (up to 13,000s-1). A difference in surface shear rate of 15%
      between the two ports was obtained. 

PMID- 24335388
TI  - Retreatment after secondary resistance or mixed response: a pilot study.
AB  - OBJECTIVE: Oncologists usually avoid retreatment with drugs to which patients
      have shown secondary resistance or a mixed response. Here, we report our findings
      in a pilot study in patients rechallenged with agents previously producing
      prolonged stable disease (SD), partial or complete remission (PR/CR) or a mixed
      response, followed by progression. RESULTS: Eleven individuals with advanced
      cancers (median number of prior systemic therapies in the metastatic setting = 4,
      range 2-7) were included (8 men; median age 57 years; median Eastern Cooperative
      Oncology Group performance status of 1). The median duration between initial
      treatment and retreatment was 92 weeks. Eight of 11 patients (73%) on a
      retreatment regimen showed SD >=24 weeks/PR/CR. Of these 8 individuals, 2 were
      retreated with the same agent(s), 1 with a different agent possessing the same
      mechanism of action (e.g., in case of an epidermal growth factor receptor
      inhibitor, using gefitinib first, then erlotinib), and 5 with the same agent(s)
      in combination with other agents. CONCLUSION: Our pilot data suggest that
      patients who develop acquired resistance after durable SD/CR/PR or who have an
      initial mixed response may attain SD >=6 months/PR/CR with a retreatment
      approach.

PMID- 24335389
TI  - Incomplete and transitory decrease of glycolysis: a new paradigm for anti
      angiogenic therapy?
AB  - During vessel sprouting, a migratory endothelial tip cell guides the sprout,
      while proliferating stalk cells elongate the branch. Tip and stalk cell
      phenotypes are not genetically predetermined fates, but are dynamically
      interchangeable to ensure that the fittest endothelial cell (EC) leads the vessel
      sprout. ECs increase glycolysis when forming new blood vessels. Genetic
      deficiency of the glycolytic activator PFKFB3 in ECs reduces vascular sprouting
      by impairing migration of tip cells and proliferation of stalk cells. PFKFB3
      driven glycolysis promotes the tip cell phenotype during vessel sprouting, since
      PFKFB3 overexpression overrules the pro-stalk activity of Notch signaling.
      Furthermore, PFKFB3-deficient ECs cannot compete with wild-type neighbors to form
      new blood vessels in chimeric mosaic mice. In addition, pharmacological PFKFB3
      blockade reduces pathological angiogenesis with modest systemic effects, likely
      because it decreases glycolysis only partially and transiently. 

PMID- 24335392
TI  - Expression of the orphan cytosolic sulfotransferase SULT1C3 in human intestine:
      characterization of the transcript variant and implications for function.
AB  - The cystolic sulfotransferse 1C3 (SULT1C3) gene was identified by computational
      analysis of the human genome and suggested to contain duplications of its last
      two exons (7a/b and 8a/b). Although the SULT1C3 isoform containing the more
      downstream exons 7b and 8b (SULT1C3d) has been expressed in Escherichia coli,
      crystallized, and characterized for activity, there is currently no evidence that
      SULT1C3 is expressed in any human tissue. Using reverse-transcription polymerase
      chain reaction, we detected SULT1C3 mRNA in the colorectal adenocarcinoma cell
      line (LS180), colon, and small intestine, but the amplified fragment contained
      the more upstream exons 7a and 8a. 3'-Rapid amplification of cDNA ends (RACE)
      confirmed that the SULT1C3 transcript expressed in LS180 cells contained exons
      7a/8a, whereas 5'-RACE identified a noncoding exon 1. Full-length SULT1C3
      transcript containing exons 7a/8a was amplified from LS180 and intestinal RNA,
      and in vitro transcription-translation of the cloned cDNA indicated that
      translation primarily began at the first of three in-frame ATG codons. Since
      SULT1C3 containing exons 7a/8a (SULT1C3a) would differ by 30 amino acids from
      SULT1C3d containing exons 7b/8b, we considered the functional implications of
      expressing one or the other isoform by generating structural models based on the
      reported crystal structure for SULT1C3d. Comparison of the structures indicated
      that five of the residues forming the substrate-binding pocket differed between
      the two isoforms, resulting in a change in both electron density and charge
      distribution along the inner wall of the substrate-binding pocket. These data
      indicate that SULT1C3 is expressed in human intestine but suggest that the
      expressed isoform is likely to differ functionally from the isoform that has been
      previously characterized. 

PMID- 24335391
TI  - Characterization of T-5 N-oxide formation as the first highly selective measure
      of CYP3A5 activity.
AB  - Almost half of prescription medications are metabolized by cytochrome P450 3A4
      and 3A5. CYP3A4 and 3A5 have significant substrate overlap, and there is
      currently no way to selectively monitor the activity of these two enzymes, which
      has led to the erroneous habit of attributing the cumulative activity to CYP3A4.
      While CYP3A4 expression is ubiquitous, CYP3A5 expression is polymorphic, with
      large individual differences in CYP3A5 expression level. The CYP3A5 genotype has
      been shown to alter the pharmacokinetics of drugs in clinical trials. We report
      the first tool compound capable of determining CYP3A5 activity in biologic
      samples containing both enzymes. Oxidation of T-5 by CYP3A5 yields an N-oxide
      metabolite that is over 100-fold selective over CYP3A4. Formation of T-5 N-oxide
      highly correlates with the CYP3A5 genotype and CYP3A5 expression levels in human
      liver microsomes and human hepatocytes. 

PMID- 24335390
TI  - Herb-drug interactions: challenges and opportunities for improved predictions.
AB  - Supported by a usage history that predates written records and the perception
      that "natural" ensures safety, herbal products have increasingly been
      incorporated into Western health care. Consumers often self-administer these
      products concomitantly with conventional medications without informing their
      health care provider(s). Such herb-drug combinations can produce untoward effects
      when the herbal product perturbs the activity of drug metabolizing enzymes and/or
      transporters. Despite increasing recognition of these types of herb-drug
      interactions, a standard system for interaction prediction and evaluation is
      nonexistent. Consequently, the mechanisms underlying herb-drug interactions
      remain an understudied area of pharmacotherapy. Evaluation of herbal product
      interaction liability is challenging due to variability in herbal product
      composition, uncertainty of the causative constituents, and often scant knowledge
      of causative constituent pharmacokinetics. These limitations are confounded
      further by the varying perspectives concerning herbal product regulation.
      Systematic evaluation of herbal product drug interaction liability, as is routine
      for new drugs under development, necessitates identifying individual constituents
      from herbal products and characterizing the interaction potential of such
      constituents. Integration of this information into in silico models that estimate
      the pharmacokinetics of individual constituents should facilitate prospective
      identification of herb-drug interactions. These concepts are highlighted with the
      exemplar herbal products milk thistle and resveratrol. Implementation of this
      methodology should help provide definitive information to both consumers and
      clinicians about the risk of adding herbal products to conventional
      pharmacotherapeutic regimens. 

PMID- 24335394
TI  - 2013 BJA/PGA Special Issue: a selection of nine educational reviews.

PMID- 24335393
TI  - Regulation of human cytosolic sulfotransferases 1C2 and 1C3 by nuclear signaling
      pathways in LS180 colorectal adenocarcinoma cells.
AB  - Cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of a myriad
      of endogenous and xenobiotic substrates. Among the 13 human SULTs, little is
      known regarding regulation of the SULT1C subfamily. We evaluated the effects of a
      panel of transcription factor activators on levels of SULT1C mRNA (1C2 and 1C3)
      and protein (1C2) in LS180 colorectal adenocarcinoma cells. Treatment with 3-[3
      [N-(2-chloro-3-trifluoromethylbenzyl)-(2,2
      diphenylethyl)amino]propyloxy]phenylacetic acid hydrochloride [GW3965, liver X
      receptor (LXR) activator], 3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4
      yl)oxymethyl-5-isopropylisoxazole [GW4064, farnesoid X receptor (FXR)], or
      rifampicin [pregnane X receptor (PXR)] moderately (<=2-fold) increased both
      SULT1C2 and SULT1C3 mRNA levels. 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3,
      vitamin D receptor (VDR)] selectively upregulated SULT1C2, whereas ciprofibrate
      [peroxisome proliferator-activated receptor alpha (PPARalpha)], rosiglitazone
      (PPARgamma), and 2,3,7,8-tetrachlorodibenzo-p-dioxin [aryl hydrocarbon receptor
      (AhR)] selectively increased SULT1C3 mRNA levels. SULT1C2 protein content was
      strongly increased by 1,25(OH)2D3 treatment and moderately increased by GW3965,
      GW4064, and rifampicin. To evaluate SULT1C2 transcriptional regulation, treatment
      effects were determined on reporter activity from transfected constructs
      containing ~10 kb of the SULT1C2 gene. Treatment with GW3965, GW4064, or
      1,25(OH)2D3 increased reporter activity ~2-, 5-, and 5.5-fold, respectively, from
      a construct containing mostly intron 1 of the SULT1C2 gene. Expression of AhR,
      LXRalpha, LXRbeta, PPARalpha, PPARgamma, PXR, and VDR was confirmed in LS180
      cells using quantitative reverse-transcription polymerase chain reaction;
      however, FXR expression was negligible, suggesting that GW4064 increased SULT1C
      expression through an FXR-independent mechanism. Collectively, our findings are
      the first to characterize the regulation of human SULT1C2 and SULT1C3 expression
      by several transcription factor activators. Further, we determined that
      responsive regions for LXR and VDR are likely contained within intron 1 of the
      SULT1C2 gene. 

PMID- 24335395
TI  - Applications of regional anaesthesia in paediatrics.
AB  - Advances in the field of paediatric regional anaesthesia have specific
      applications to both acute and chronic pain management. This review summarizes
      data regarding the safety of paediatric regional anaesthetic techniques. Current
      guidelines are provided for performing paediatric regional techniques, with a
      focus on applications for postoperative pain management. Brief descriptions of
      relevant anatomy followed by indications for commonly performed blocks are
      highlighted along with the potential of adverse side-effects. 

PMID- 24335396
TI  - Glycaemic control in the perioperative period.
AB  - The prevalence of type 2 diabetes mellitus and the potential for perioperative
      dysglycaemia (hyperglycaemia, hypoglycaemia, stress-induced hyperglycaemia, or
      glucose variability) continue to increase dramatically. The majority of
      investigations on perioperative glycaemic control focused on critically ill
      patients and concentrated on goals of therapy, level of intensity of insulin
      infusion, feeding regimes, concerns over hypoglycaemia, and promulgation of
      recent guidelines calling for less strict glucose control. Areas of perioperative
      glycaemic control that deserve further investigation include preoperative
      identification of patients with undiagnosed type 2 diabetes and other forms of
      dysglycaemia, determination of appropriate intraoperative glucose goals, and
      establishment of the impact and natural history of perioperative abnormalities in
      glucose homeostasis. In the heterogeneous adult perioperative population, it is
      unlikely that one standard of perioperative glycaemic control is appropriate for
      all patients. This review presents recent evidence and expert guidance to aid
      preoperative assessment, intraoperative management, and postoperative care of the
      dysglycaemic adult patient. 

PMID- 24335397
TI  - Perioperative management of antiplatelet therapy.
AB  - Worldwide, cardiovascular events represent the major cause of morbidity and
      mortality. A key role in the pathogenesis of these events is played by platelets.
      Interventional procedures, with placement of coronary and vascular stents, often
      represent the preferred therapeutic strategy. Antiplatelet medications are
      considered first-line therapy in preventing cardiovascular thrombotic events. A
      wide array of antiplatelet agents is available, each with different
      pharmacological properties. When patients on antiplatelet agents present for
      surgery, the perioperative team must design an optimal strategy to manage
      antiplatelet medications. Each patient is stratified according to risk of
      developing a cardiovascular thrombotic event and inherent risk of surgical
      bleeding. After risk stratification analysis, various therapeutic pathways
      include continuing or discontinuing all antiplatelet agents or maintaining one
      antiplatelet agent and discontinuing the other. This review focuses on the
      pharmacological and pharmacokinetic properties of both older and novel
      antiplatelet drugs, and reviews current literature and guidelines addressing
      options for perioperative antiplatelet management. 

PMID- 24335398
TI  - Perioperative factor concentrate therapy.
AB  - Transfusion of allogeneic plasma has been a life-saving measure for decades in
      patients with severe trauma or suffering from major surgical blood loss. The
      safety of allogeneic blood components has improved in terms of pathogen
      transmission, but haemostatic efficacy of plasma is hindered by the large volume
      and time required for thawing and infusion. Several plasma-derived and
      recombinant factor concentrates are clinically available and indicated for
      targeted replacement of missing coagulation elements in hereditary disorders of
      thrombosis and haemostasis. When used appropriately, factor concentrate therapy
      can rapidly restore deficient factor(s) without causing volume overload. The
      haemostatic defect in perioperative patients is often multifactorial, and
      therefore careful clinical judgement and timely coagulation testing must be
      exercised before the administration of factor concentrates. In this review, the
      rationale for including factor concentrates in perioperative haemostatic
      management will be discussed in conjunction with the limitations of plasma
      transfusion. 

PMID- 24335399
TI  - Monitoring and managing hepatic disease in anaesthesia.
AB  - Patients with liver disease have multisystem organ dysfunction that leads to
      physiological perturbations ranging from hyperbilirubinaemia of no clinical
      consequence to severe coagulopathy and metabolic disarray. Patient-specific risk
      factors, clinical scoring systems, and surgical procedures stratify perioperative
      risk for these patients. The anaesthetic management of patients with hepatic
      dysfunction involves consideration of impaired drug metabolism, hyperdynamic
      circulation, perioperative hypoxaemia, bleeding, thrombosis, and hepatic
      encephalopathy. 

PMID- 24335400
TI  - Aged erythrocytes: a fine wine or sour grapes?
AB  - Blood transfusion saves many lives but carries significant risk of injury.
      Currently, red blood cell (RBC) concentrates can be stored up to 42 days.
      Concerns have recently been raised about the safety and efficacy of transfusing
      stored RBCs. Refrigerated storage results in a 'storage lesion' that is reflected
      by metabolic derangements, RBC shape modification, rheological changes, oxidative
      injury to lipids and proteins, alterations in oxygen affinity and delivery,
      increased adhesion of RBCs to endothelial cells, and accumulation of bioactive
      substances in storage media. In animal models, transfusion of aged, but not
      fresh, RBCs induces organ injury, inflammation, coagulopathy, and impaired oxygen
      delivery. A number of clinical studies, mostly observational or retrospective and
      from a single centre, have reported an association between transfusion of older
      RBCs and increased clinically significant outcomes, such as increased morbidity
      and mortality in certain patient populations, including trauma, critical care,
      and cardiac surgery. Others, however, have failed to indicate an influence of RBC
      age on outcome. The quality of evidence is currently too poor to make
      recommendations to change current transfusion practice; however, the transfusion
      community looks forward to the results of randomized trials currently addressing
      the long-standing question regarding the effects of RBC storage on clinically
      significant outcomes. 

PMID- 24335401
TI  - Update on massive transfusion.
AB  - Massive haemorrhage requires massive transfusion (MT) to maintain adequate
      circulation and haemostasis. For optimal management of massively bleeding
      patients, regardless of aetiology (trauma, obstetrical, surgical), effective
      preparation and communication between transfusion and other laboratory services
      and clinical teams are essential. A well-defined MT protocol is a valuable tool
      to delineate how blood products are ordered, prepared, and delivered; determine
      laboratory algorithms to use as transfusion guidelines; and outline duties and
      facilitate communication between involved personnel. In MT patients, it is
      crucial to practice damage control resuscitation and to administer blood products
      early in the resuscitation. Trauma patients are often admitted with early trauma
      induced coagulopathy (ETIC), which is associated with mortality; the aetiology of
      ETIC is likely multifactorial. Current data support that trauma patients treated
      with higher ratios of plasma and platelet to red blood cell transfusions have
      improved outcomes, but further clinical investigation is needed. Additionally,
      tranexamic acid has been shown to decrease the mortality in trauma patients
      requiring MT. Greater use of cryoprecipitate or fibrinogen concentrate might be
      beneficial in MT patients from obstetrical causes. The risks and benefits for
      other therapies (prothrombin complex concentrate, recombinant activated factor
      VII, or whole blood) are not clearly defined in MT patients. Throughout the
      resuscitation, the patient should be closely monitored and both metabolic and
      coagulation abnormalities corrected. Further studies are needed to clarify the
      optimal ratios of blood products, treatment based on underlying clinical
      disorder, use of alternative therapies, and integration of laboratory testing
      results in the management of massively bleeding patients. 

PMID- 24335402
TI  - Obstructive sleep apnoea in children: perioperative considerations.
AB  - Obstructive sleep apnoea (OSA) has become a major public health concern as its
      incidence and severity have increased in tandem with the obesity epidemic. In
      children, OSA is now recognized as a common disorder and can be associated with
      significant morbidity. OSA belongs to a spectrum of diagnoses known as sleep
      related breathing disorders in which the airway is completely (apnoea) or
      partially (hypopnoea) occluded during sleep despite continued respiratory
      efforts. This airway obstruction can cause abnormal gas exchange leading to
      hypoxaemia, hypercapnia, sleep fragmentation, and their attendant physiological
      and behavioural consequences. The degrees of hypercapnia, hypoxaemia, and upper
      airway airflow reduction are the primary factors determining the severity of OSA.
      In young children, adenotonsillar hypertrophy is the most common anatomical
      abnormality associated with OSA, and adenotonsillectomy is, therefore, the most
      common surgical intervention. Perioperative complications associated with
      adenotonsillectomy are more common in children with severe OSA. A thorough
      understanding of the pathophysiology of OSA, careful and complete preoperative
      assessment, meticulous intraoperative and postoperative management, and early
      recognition of potential perioperative complications are essential to
      optimization of outcomes. The safe anaesthetic management of a child with OSA
      requires an anaesthetic technique tailored to the underlying aetiology and
      severity of OSA and the surgical procedure. This review focuses on the
      epidemiology, pathogenesis, and diagnosis of OSA, and the state-of-the-art and
      future directions in the perioperative management of children with OSA. 

PMID- 24335403
TI  - New oral anticoagulants and regional anaesthesia.
AB  - The new oral anticoagulants are approved for a variety of clinical syndromes,
      including the prevention of stroke in atrial fibrillation, acute coronary
      syndromes, treatment of venous thromboembolism (VTE), and prevention of venous
      thrombosis after total joint surgery or hip fracture. Published guidelines have
      differing recommendations on the safe interval between discontinuation of the
      anticoagulant and performance of neuraxial procedures and between the
      interventional procedure and redosing of the drug. While two to three half-life
      intervals might be acceptable in patients who are at high risk for VTE or stroke,
      an interval of four to six half-lives between discontinuation of the drug and
      neuraxial injections is probably safer in most patients at low risk of
      thrombosis. In those with renal disease, the interval should be based on
      creatinine clearance. After a neuraxial procedure or removal of an epidural
      catheter, anticoagulants can be resumed within 24-48 h in most patients, but they
      can be taken sooner in patients who are at higher risk for VTE or stroke, that
      is, 24 h minus the time to peak effect of the drug. The new antiplatelet drugs
      prasugrel and ticagrelor should be stopped 7 or 5 days, respectively, before a
      neuraxial injection and can be restarted 24 h later. In selected situations,
      laboratory monitoring of the anticoagulant effect is appropriate, and reversal
      agents are suggested when there is a need to rapidly restore haemostatic
      function. 

PMID- 24335410
TI  - "There will be blood" from fibroblasts.

PMID- 24335411
TI  - Early overfeed-induced obesity leads to brown adipose tissue hypoactivity in
      rats.
AB  - BACKGROUND/AIMS: Brown adipose tissue activation has been considered a potential
      anti-obesity mechanism because it is able to expend energy through thermogenesis.
      In contrast, white adipose tissue stores energy, contributing to obesity. We
      investigated whether the early programming of obesity by overfeeding during
      lactation changes structure of interscapular brown adipose tissue in adulthood
      and its effects on thermogenesis. METHODS: Birth of litters was considered day 0.
      On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters.
      On day 21, the litters were weaned. A temperature transponder was implanted
      underneath interscapular brown adipose tissue pads of 81-day-old animals; local
      temperature was measured during light and dark periods between days 87 and 90.
      The animals were euthanized, and tissue and blood samples were collected for
      further analysis. The vagus and retroperitoneal sympathetic nerve activity was
      recorded. RESULTS: Small litter rats presented significant lower interscapular
      brown adipose tissue temperature during the light (NL 37.6 degrees C vs. SL 37.2
      degrees C) and dark (NL 38 degrees C vs. SL 37.6 degrees C) periods compared to
      controls. Morphology of small litter brown adipose tissue showed fewer lipid
      droplets in the tissue center and more and larger in the periphery. The activity
      of vagus nerve was 19,9% greater in the small litter than in control (p<0.01),
      and no difference was observed in the sympathetic nerve activity. In adulthood,
      the small litter rats were 11,7% heavier than the controls and presented higher
      glycemia 13,1%, insulinemia 70% and corticosteronemia 92,6%. CONCLUSION: Early
      overfeeding programming of obesity changes the interscapular brown adipose tissue
      structure in adulthood, leading to local thermogenesis hypoactivity, which may
      contribute to obesity in adults.

PMID- 24335412
TI  - Enhanced recovery after surgery: a survey among anaesthesiologists from 27
      countries.

PMID- 24335413
TI  - Effect of head rotation during surgery in the prone position on regional cerebral
      oxygen saturation: A prospective controlled study.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) has been used to study regional
      cerebral blood oxygen saturation (rScO2) in patients in the prone position.
      OBJECTIVES: We aimed to test the hypothesis that head rotation more than 45
      degrees  would affect the rScO2. DESIGN: A prospective, controlled, single cohort
      study. SETTING: University Hospital specialising in spinal surgery. PATIENTS:
      Fifty-two patients undergoing spinal surgery in prone position were enrolled and
      48 completed the study. INTERVENTIONS: NIRS sensors were attached to each side of
      the forehead. Measurements were conducted during steady-state anaesthesia with
      the head in the neutral position, rotated left, rotated right and returned to the
      neutral position. Each series consisted of three measurements: resting on the
      head support, during head lift (to relieve pressure on the tissue at the sensors)
      and returned to rest on the head support. MAIN OUTCOME MEASURES: The differences
      in rScO2 between the neutral and the turned head positions. RESULTS: For both
      left and right sensors, the median differences in rScO2 between neutral and left
      or right positions were between 0 and -1 with the head up (P = 0.14 to 0.84). The
      median differences with the head down were between 3.8 and -0.8, with a
      significant difference for the left sensor when turned left (P < 0.01) and for
      the right sensor (P = 0.006) when turned right. Ten patients showed reductions of
      more than 10 in rScO2 in the rotated (and lifted) positions. When the head was
      lifted from the head support, the rScO2 was -0.5 to 3.75 units higher, but there
      was high variability between patients. CONCLUSION: We recommend the neutral head
      position for prone patients.TRIAL REGISTRATION clinicaltrials.gov Identifier:
      NCT01760369.

PMID- 24335414
TI  - The relationship between red blood cell distribution width and myocardial
      ischemia in dobutamine stress echocardiography.
AB  - OBJECTIVES: Although elevated red blood cell distribution width (RDW) is
      associated with adverse outcomes in patients with cardiovascular disease, its
      role in demonstrating the presence and extent of myocardial ischemia for coronary
      artery disease is not known. The purpose of this study is to investigate the
      relationship between RDW and myocardial ischemia by using dobutamine stress
      echocardiography (DSE). METHODS: A total of 917 patients were included in this
      prospective study. A complete blood analysis was performed for RDW before DSE.
      According to DSE results, patients were divided into two groups: DSE negative and
      DSE positive. According to the number of ischemic segments in DSE, patients were
      divided into three groups: no-ischemic segment, 1-3 ischemic segments, and >=4
      ischemic segments. In addition, coronary angiography results of DSE-positive
      groups were assessed in respect of RDW. RESULTS: The RDW of the DSE-positive
      group (n=277) was higher than for the DSE-negative group (n=640) (13.5+/-1.5 vs.
      12.7+/-1.3%, P<0.001, respectively). Elevated RDW values were also related to
      higher number of ischemic segments (no-ischemic segment group: 12.7+/-1.3, 1-3
      ischemic segments group: 13.2+/-1.5, and >=4 ischemic segments group: 14.2+/-1.3,
      P<0.001). A receiver operating curve analysis showed a cut-off value of RDW
      greater than 13.5% for predicting myocardial ischemia (sensitivity: 57.0%,
      specificity: 77.8%, positive predictive value: 52.7%, negative predictive value:
      80.7%). In addition, positive predictive value of DSE was increased from 82.4 to
      94.2% for detecting coronary artery disease by coronary angiography, when RDW
      (>13.5%) was used. CONCLUSION: RDW is related to the presence and extent of
      myocardial ischemia in DSE. A high RDW increases the diagnostic accuracy of DSE.

PMID- 24335415
TI  - Cellular photo digital breathalyzer for monitoring alcohol use: a pilot study.
AB  - BACKGROUND: Monitoring alcohol use is important in numerous situations. Direct
      ethanol metabolites, such as ethyl glucuronide (EtG), have been shown to be
      useful tools in detecting alcohol use and documenting abstinence. For very
      frequent or continuous control of abstinence, they lack practicability.
      Therefore, devices measuring ethanol itself might be of interest. This pilot
      study aims at elucidating the usability and accuracy of the cellular photo
      digital breathalyzer (CPDB) compared to self-reports in a naturalistic setting.
      METHOD: 12 social drinkers were included. Subjects used a CPDB 4 times daily,
      kept diaries of alcohol use and submitted urine for EtG testing over a period of
      5 weeks. RESULTS: In total, the 12 subjects reported 84 drinking episodes. 1,609
      breath tests were performed and 55 urine EtG tests were collected. Of 84 drinking
      episodes, CPDB detected 98.8%. The compliance rate for breath testing was 96%. Of
      the 55 EtG tests submitted, 1 (1.8%) was positive. CONCLUSIONS: The data suggest
      that the CPDB device holds promise in detecting high, moderate, and low alcohol
      intake. It seems to have advantages compared to biomarkers and other monitoring
      devices. The preference for CPDB by the participants might explain the high
      compliance. Further studies including comparison with biomarkers and transdermal
      devices are needed.

PMID- 24335416
TI  - Amyloid-beta increases metallo- and cysteine protease activities in human
      macrophages.
AB  - BACKGROUND/AIMS: Amyloid-beta (Abeta) plays a crucial role in the onset and
      progression of atherosclerosis. Macrophages are a source of matrix
      metalloproteinases (MMPs), cysteine proteases and transforming growth factor
      (TGF)-beta1 in the vascular wall. The aims of this study were to analyze the
      capacity of Abeta peptide (1-40) (Abeta40), Abeta peptide (1-42) (Abeta42) and
      fibrillar Abeta42 (fAbeta42) to modulate the expression and activity of MMP-9,
      MMP-2 and tissue inhibitor of MMP-1 (TIMP-1) in human monocyte-derived
      macrophages (HMDM). Additionally, we analyzed whether Abeta internalization
      alters the secretion of cathepsin S (CatS) and TGF-beta1 by macrophages. METHODS:
      HMDM were exposed to native and fibrillar Abeta. MMPs and TIMP-1 expression was
      analyzed by real-time PCR, and MMP abundance by zymography. Protein levels of
      precursor and active forms of CatS were analyzed by Western blot and TGF-beta1
      levels by ELISA. RESULTS: Abeta40, Abeta42 and especially fAbeta42 strongly
      induced MMP-9/MMP-2 levels. Moreover, we showed enhanced active CatS and reduced
      TGF-beta1 protein levels in the secretome of Abeta42 and fAbeta42-exposed
      macrophages. CONCLUSIONS: Abeta can regulate the proinflammatory state of human
      macrophages by inducing metallo- and cysteine protease levels and by reducing TGF
      beta1 secretion. These effects may be crucial in atherosclerosis progression.

PMID- 24335417
TI  - [Chemokines and allergy].

PMID- 24335418
TI  - [Role of IL-25 and IL-33 in allergic diseases].

PMID- 24335419
TI  - [Guideline for the management of latex allergy and safe rubber use in health care
      facility -one point advice-].

PMID- 24335420
TI  - [Autoinflammatory diseases reach adolescence].

PMID- 24335421
TI  - [Differential diagnosis and treatment of chronic cough].

PMID- 24335422
TI  - [Patient education of allergic diseases in childhood -focused on the management
      of childhood asthma in home life-].

PMID- 24335423
TI  - [Identification of 70 kDa shrimp protein as a possible new allergen for shrimp
      allergy].
AB  - BACKGROUND: A large-scale study of causative allergen components of shrimp
      allergies has never been conducted in Japan. SUBJECTS: A total of 31 patients
      with shrimp allergy who were referred to the Kakogawa Prefectural Medical Center
      from January 2004 to August 2011 were enrolled in the study. Shrimp allergy was
      diagnosed according to the clinical symptoms, and positive prick testing using
      black tiger shrimp. METHODS: Serum-specific IgE to two preparations of shrimp
      allergens (shrimp: shrimp extracts used before June 2012; and new shrimp: shrimp
      extracts used after July 2012 for ImmunoCAP(r)) and tropomyosin was determined
      with ImmunoCAP(r) (CAP-FEIA, Phadia) . Western blot analysis was performed using
      soluble and insoluble fractions from black tiger shrimp to define the causative
      shrimp allergens. RESULTS: In 31 cases of shrimp allergy, detection rate (more
      than class 1) of allergen-specific IgE to conventional shrimp was 58.1%, to new
      shrimp was 66.7%, and to tropomyosin was 29.0%. Positive rate (more than class 2)
      of allergen-specific IgE to conventional shrimp was 54.8%, to new shrimp was
      55.0%, and to tropomyosin was 19.4%. In the 5 cases of FDEIA, detection rate of
      allergen-specific IgE to conventional shrimp was 20%, to new shrimp was 40%, and
      to tropomyosin was 0%. In the 19 cases of immediate-type allergy, detection rate
      of allergen-specific IgE to conventional shrimp was 68.4%, to new shrimp was
      66.7%, and to tropomyosin was 36.8%. In the 7 cases of OAS, detection rate of
      allergen-specific IgE to shrimp was 57.1%, to new shrimp was 85.7%, and to
      tropomyosin was 28.5%. Western blot analysis of the 31 cases showed that several
      cases showed a band with a molecular weight of 35-38 kDa, which corresponds to
      tropomyosin. However, a 70-kDa band was detected in 30 of 31 cases. CONCLUSION:
      The 70-kDa protein may be a new major allergen component of shrimp allergy.

PMID- 24335424
TI  - [Establishment of "Anaphylaxis Scoring Aichi (ASCA)," a new symptom scoring
      system to be used in an oral food challenge (OFC)].
AB  - BACKGROUND: An original symptom score sheet named "Anaphylaxis Scoring Aichi
      (ASCA)" was created to quantitatively determine the severity of allergic symptoms
      provoked in an oral food challenge. METHODS: ASCA lists and sorts subjective and
      objective symptoms into five organs (respiratory, skin-mucosal, gastrointestinal,
      psycho-neurological and cardiovascular). The organ scores were given (0 to 60
      points) in accordance with the severity of each symptom. The total score was
      defined as the sum of the highest 5 organ scores (maximum 240 points) observed
      throughout the course of an OFC. This study evaluated the ASCA score in 253 cases
      of a positive food challenge (age 1-16 years, mean 5.3+/-3.2 years) conducted
      from April to August 2011 in our institute. The results were compared to the
      modified anaphylaxis grading presented in the Japanese Pediatric Guideline for
      Oral Food Challenge Test in Food Allergy 2009. At the same time, we evaluated the
      indications of symptomatic treatment using ASCA score. RESULTS: The total score
      closely correlated with the anaphylaxis grading, but there was a wide range of
      overlap between grade 2 and grade 3. All cases with a total score>=60 points were
      equivalent to grade 4 or 5, and that were consisted of three or more organ
      symptoms. These severe cases contained respiratory or skin/mucosal symptoms, and
      despite the early induction of initial therapy, the symptoms became worse.
      CONCLUSION: ASCA is therefore considered to be a useful tool for use in an oral
      food challenge test.

PMID- 24335425
TI  - [Two cases of refractory asthma presenting chest pain, which were successfully
      treated with noninvasive positive pressure ventilation].
AB  - We report here two cases of refractory asthma presenting chest pain, which were
      successfully treated by using intermittent noninvasive positive pressure
      ventilation (NPPV). Both patients were women, and were diagnosed to have
      bronchial asthma with the reversibility of airway contraction after
      administration of a bronchodilator. Although both patients were treated with
      several medicines for "treatment step 4" based on the guideline in Japan, their
      asthma could not be controlled well and their symptoms including the chest pain
      eroded their quality of life. We tried to use NPPV for 30 minutes in our clinic,
      and their symptoms improved. Therefore, we innovated for them intermittent NPPV
      as a home treatment. After 3 to 5 months, their asthma, including the symptom of
      chest pain, improved. In addition, pulmonary function tests revealed stable vital
      capacity and forced expiratory volume in 1 second in all cases after the NPPV
      therapy, while V50 and V25 were improved. These results suggest that NPPV may be
      a useful treatment option for patients with refractory asthma, especially those
      presenting chest pain. 

PMID- 24335426
TI  - Quantifying and comparing phylogenetic evolutionary rates for shape and other
      high-dimensional phenotypic data.
AB  - Many questions in evolutionary biology require the quantification and comparison
      of rates of phenotypic evolution. Recently, phylogenetic comparative methods have
      been developed for comparing evolutionary rates on a phylogeny for single,
      univariate traits (sigma(2)), and evolutionary rate matrices (R) for sets of
      traits treated simultaneously. However, high-dimensional traits like shape remain
      under-examined with this framework, because methods suited for such data have not
      been fully developed. In this article, I describe a method to quantify
      phylogenetic evolutionary rates for high-dimensional multivariate data (sigma2
      mult), found from the equivalency between statistical methods based on covariance
      matrices and those based on distance matrices (R-mode and Q-mode methods). I then
      use simulations to evaluate the statistical performance of hypothesis-testing
      procedures that compare sigma2 mult for two or more groups of species on a
      phylogeny. Under both isotropic and non-isotropic conditions, and for differing
      numbers of trait dimensions, the proposed method displays appropriate Type I
      error and high statistical power for detecting known differences in sigma2 mult
      among groups. In contrast, the Type I error rate of likelihood tests based on the
      evolutionary rate matrix (R) increases as the number of trait dimensions (p)
      increases, and becomes unacceptably large when only a few trait dimensions are
      considered. Further, likelihood tests based on R cannot be computed when the
      number of trait dimensions equals or exceeds the number of taxa in the phylogeny
      (i.e., when p >= N). These results demonstrate that tests based on sigma2 mult
      provide a useful means of comparing evolutionary rates for high-dimensional data
      that are otherwise not analytically accessible to methods based on the
      evolutionary rate matrix. This advance thus expands the phylogenetic comparative
      toolkit for high-dimensional phenotypic traits like shape. Finally, I illustrate
      the utility of the new approach by evaluating rates of head shape evolution in a
      lineage of Plethodon salamanders.

PMID- 24335427
TI  - Species radiation by niche shifts in New Zealand's rockcresses (Pachycladon,
      Brassicaceae).
AB  - Adaptive radiations such as the Darwin finches in the Galapagos or the cichlid
      fishes from the Eastern African Great Lakes have been a constant source of
      inspiration for biologists and a stimulus for evolutionary thinking. A central
      concept behind adaptive radiation is that of evolution by niche shifts, or
      ecological speciation. Evidence for adaptive radiations generally requires a
      strong correlation between phenotypic traits and the environment. But adaptive
      traits are often cryptic, hence making this phenotype-environment approach
      difficult to implement. Here we propose a procedure for detecting adaptive
      radiation that focuses on species' ecological niche comparisons. It evaluates
      whether past ecological disparity in a group fits better a neutral Brownian
      motion model of ecological divergence or a niche shift model. We have evaluated
      this approach on New Zealand rockcresses (Pachycladon) that recently radiated in
      the New Zealand Alps. We show that the pattern of ecological divergence rejects
      the neutral model and is consistent with that of a niche shift model. Our
      approach to detect adaptive radiation has the advantage over alternative
      approaches that it focuses on ecological niches, a key concept behind adaptive
      radiation. It also provides a way to evaluate the importance of ecological
      speciation in adaptive radiations and will have general application in
      evolutionary studies. In the case of Pachycladon, the high estimated
      diversification rate, the distinctive ecological niches of species, and the
      evidence for ecological speciation suggest a remarkable example of adaptive
      radiation. 

PMID- 24335428
TI  - Missing data estimation in morphometrics: how much is too much?
AB  - Fossil-based estimates of diversity and evolutionary dynamics mainly rely on the
      study of morphological variation. Unfortunately, organism remains are often
      altered by post-mortem taphonomic processes such as weathering or distortion.
      Such a loss of information often prevents quantitative multivariate description
      and statistically-controlled comparisons of extinct species based on morphometric
      data. A common way to deal with missing data involves imputation methods that
      directly fill the missing cases with model estimates. Over the last years,
      several empirically-determined thresholds for the maximum acceptable proportion
      of missing values have been proposed in the literature, whereas other studies
      showed that this limit actually depends on various properties of the study data
      set and of the selected imputation method, and is by no way generalizable. We
      evaluate the relative performances of seven multiple imputation (MI) techniques
      through a simulation-based analysis under three distinct patterns of missing data
      distribution. Overall, Fully Conditional Specification and Expectation
      Maximization algorithms provide the best compromises between imputation accuracy
      and coverage probability. MI techniques appear remarkably robust to the violation
      of basic assumptions such as the occurrence of taxonomically or anatomically
      biased patterns of missing data distribution, making differences in simulation
      results between the three patterns of missing data distribution much smaller than
      differences between the individual MI techniques. Based on these results, rather
      than proposing a new (set of) threshold value(s), we develop an approach
      combining the use of MIs with procrustean superimposition of principal component
      analysis results, in order to directly visualize the effect of individual missing
      data imputation on an ordinated space. We provide an R function for users to
      implement the proposed procedure. 

PMID- 24335429
TI  - Coalescent species delimitation in milksnakes (genus Lampropeltis) and impacts on
      phylogenetic comparative analyses.
AB  - Both gene-tree discordance and unrecognized diversity are sources of error for
      accurate estimation of species trees, and can affect downstream diversification
      analyses by obscuring the correct number of nodes, their density, and the lengths
      of the branches subtending them. Although the theoretical impact of gene-tree
      discordance on evolutionary analyses has been examined previously, the effect of
      unsampled and cryptic diversity has not. Here, we examine how delimitation of
      previously unrecognized diversity in the milksnake (Lampropeltis triangulum) and
      use of a species-tree approach affects both estimation of the Lampropeltis
      phylogeny and comparative analyses with respect to the timing of diversification.
      Coalescent species delimitation indicates that L. triangulum is not monophyletic
      and that there are multiple species of milksnake, which increases the known
      species diversity in the genus Lampropeltis by 40%. Both genealogical and
      temporal discordance occurs between gene trees and the species tree, with
      evidence that mitochondrial DNA (mtDNA) introgression is a main factor. This
      discordance is further manifested in the preferred models of diversification,
      where the concatenated gene tree strongly supports an early burst of speciation
      during the Miocene, in contrast to species-tree estimates where diversification
      follows a birth-death model and speciation occurs mostly in the Pliocene and
      Pleistocene. This study highlights the crucial interaction among coalescent-based
      phylogeography and species delimitation, systematics, and species diversification
      analyses. 

PMID- 24335430
TI  - Partial sequence homogenization in the 5S multigene families may generate
      sequence chimeras and spurious results in phylogenetic reconstructions.
AB  - Multigene families have provided opportunities for evolutionary biologists to
      assess molecular evolution processes and phylogenetic reconstructions at deep and
      shallow systematic levels. However, the use of these markers is not free of
      technical and analytical challenges. Many evolutionary studies that used the
      nuclear 5S rDNA gene family rarely used contiguous 5S coding sequences due to the
      routine use of head-to-tail polymerase chain reaction primers that are anchored
      to the coding region. Moreover, the 5S coding sequences have been concatenated
      with independent, adjacent gene units in many studies, creating simulated
      chimeric genes as the raw data for evolutionary analysis. This practice is based
      on the tacitly assumed, but rarely tested, hypothesis that strict intra-locus
      concerted evolution processes are operating in 5S rDNA genes, without any
      empirical evidence as to whether it holds for the recovered data. The potential
      pitfalls of analysing the patterns of molecular evolution and reconstructing
      phylogenies based on these chimeric genes have not been assessed to date. Here,
      we compared the sequence integrity and phylogenetic behavior of entire versus
      concatenated 5S coding regions from a real data set obtained from closely related
      plant species (Medicago, Fabaceae). Our results suggest that within arrays
      sequence homogenization is partially operating in the 5S coding region, which is
      traditionally assumed to be highly conserved. Consequently, concatenating 5S
      genes increases haplotype diversity, generating novel chimeric genotypes that
      most likely do not exist within the genome. In addition, the patterns of gene
      evolution are distorted, leading to incorrect haplotype relationships in some
      evolutionary reconstructions. 

PMID- 24335431
TI  - TAS-106: preclinical, clinical and beyond.
AB  - 5-Fluorouracil, other fluorinated pyrimidines and their derivatives are
      frequently used in chemotherapy to treat different types of cancer. These agents
      are classified as metabolic antagonists that target the DNA synthesis phase of
      the cell cycle. Therefore, these agents are more effective in rapidly growing
      tumors than in more indolent cancers. In order to develop new drugs that
      interfere with both DNA and RNA synthesis, the metabolism of pyrimidines was
      investigated, and new compounds were developed by the molecular design method,
      which analyzes the biochemical properties of the compounds. The nucleoside 3'-C
      ethynylcytidine (TAS-106) was designed to inhibit RNA synthesis by blocking RNA
      polymerases I, II, and III, which occur throughout the cell cycle except for the
      M phase. This review article discusses the antitumor activity of TAS-106 as a
      single agent or in combination therapy with the focus on preclinical and clinical
      findings.

PMID- 24335432
TI  - RNA polymerase is a powerful torsional motor.

PMID- 24335433
TI  - Biologically inspired intelligent decision making: a commentary on the use of
      artificial neural networks in bioinformatics.
AB  - Artificial neural networks (ANNs) are a class of powerful machine learning models
      for classification and function approximation which have analogs in nature. An
      ANN learns to map stimuli to responses through repeated evaluation of exemplars
      of the mapping. This learning approach results in networks which are recognized
      for their noise tolerance and ability to generalize meaningful responses for
      novel stimuli. It is these properties of ANNs which make them appealing for
      applications to bioinformatics problems where interpretation of data may not
      always be obvious, and where the domain knowledge required for deductive
      techniques is incomplete or can cause a combinatorial explosion of rules. In this
      paper, we provide an introduction to artificial neural network theory and review
      some interesting recent applications to bioinformatics problems. 

PMID- 24335435
TI  - Basal cell origins of smoking-induced airway epithelial disorders.

PMID- 24335434
TI  - Epidemiology of severe sepsis.
AB  - Severe sepsis is a leading cause of death in the United States and the most
      common cause of death among critically ill patients in non-coronary intensive
      care units (ICU). Respiratory tract infections, particularly pneumonia, are the
      most common site of infection, and associated with the highest mortality. The
      type of organism causing severe sepsis is an important determinant of outcome,
      and gram-positive organisms as a cause of sepsis have increased in frequency over
      time and are now more common than gram-negative infections. Recent studies
      suggest that acute infections worsen pre-existing chronic diseases or result in
      new chronic diseases, leading to poor long-term outcomes in acute illness
      survivors. People of older age, male gender, black race, and preexisting chronic
      health conditions are particularly prone to develop severe sepsis; hence
      prevention strategies should be targeted at these vulnerable populations in
      future studies. 

PMID- 24335436
TI  - ER stress response mechanisms in the pathogenic yeast Candida glabrata and their
      roles in virulence.
AB  - The maintenance of endoplasmic reticulum (ER) homeostasis is critical for
      numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation
      of misfolded proteins in the ER (ER stress) by activating the unfolded protein
      response (UPR), an intracellular signaling pathway that adjusts the folding
      capacity of the ER. Recent studies of several pathogenic fungi have revealed that
      the UPR is important for antifungal resistance and virulence; therefore, the
      pathway has attracted much attention as a potential therapeutic target. While the
      UPR is highly conserved among eukaryotes, our group recently discovered that the
      pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses
      alternative mechanisms to cope with ER stress. This review summarizes how C.
      glabrata responds to ER stress and discusses the impacts of ER quality control
      systems on antifungal resistance and virulence. 

PMID- 24335437
TI  - beta3-adrenoceptor mediates metabolic protein remodeling in a rabbit model of
      tachypacing-induced atrial fibrillation.
AB  - BACKGROUND: The beta 3-adrenoceptor (beta3-AR) is closely associated with energy
      metabolism. This study aimed to explore the role of beta3-AR in energy remodeling
      in a rabbit model of pacing-induced atrial fibrillation (AF). METHODS: Rabbits
      with a sham-operation or pacing-induced AF were used for this study, and the
      latter group was further divided into three subgroups: 1) the pacing group, 2)
      the beta3-AR agonist (BRL37344)-treated group, and 3) the beta3-AR antagonist
      (SR59230A)-treated group. Atrial electrogram morphology and surface ECG were used
      to monitor the induction of AF and atrial effective refractory period (AERP). RT
      PCR and western blot (WB) were used to show alterations in beta3-AR and metabolic
      related protein. RESULTS: RT-PCR and WB results showed that beta3-AR was
      significantly upregulated in the pacing group, and that it corresponded with high
      AF inducibility and significantly decreased AERP200 and ATP production in this
      group. Inhibition of beta3-AR decreased the AF induction rate, reversed AERP200
      reduction, and restored ATP levels in the AF rabbits. Further activation of beta3
      AR using agonist BRL37344 exacerbated AF-induced metabolic disruption. Periodic
      acid Schiff (PAS) and Oil Red O staining showed beta3-AR-dependent glycogen and
      lipid droplet accumulation in cardiac myocytes with AF. Glucose transporter-4
      (GLUT-4) and CD36, key transporters of glucose and fatty acids, were
      downregulated in the pacing group. Expression of carnitine-palmitoyltransferase I
      (CPT-1), a key regulator in fatty acid metabolism, was also significantly
      downregulated in the pacing group. Reduced glucose transportation and fatty acid
      oxidation could be restored by inhibition of beta3-AR. Furthermore, key
      regulators of metabolism, peroxisome proliferator-activated receptor-alpha
      (PPARalpha) and PPAR co-activator (PGC-1alpha) can be regulated by
      pharmacological intervention of the beta3-AR. CONCLUSIONS: beta3-AR is involved
      in metabolic protein remodeling in AF. PPARalpha/PGC-1alpha signaling pathway
      might be the relevant down-stream molecular machinery in response to AF-induced
      activation of beta3-AR. beta3-AR might be a novel target in AF treatment.

PMID- 24335438
TI  - Developmental stage-specific transformation of neural progenitors.

PMID- 24335439
TI  - Activation of a medical emergency team using an electronic medical recording
      based screening system*.
AB  - OBJECTIVES: To evaluate the efficacy of a medical emergency team activated using
      24-hour monitoring by electronic medical record-based screening criteria followed
      by immediate intervention by a skilled team. DESIGN: Retrospective cohort study.
      SETTING: Academic tertiary care hospital with approximately 2,700 beds. PATIENTS:
      A total of 3,030 events activated by a medical emergency team from March 1, 2008,
      to February 28, 2010. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We
      collected data for all medical emergency team activations: patient
      characteristics, trigger type for medical emergency team (electronic medical
      record-based screening vs calling criteria), interventions during each event,
      outcomes of the medical emergency team intervention, and 28-day mortality after
      medical emergency team activation. We analyzed data for 2009, when the medical
      emergency team functioned 24 hours a day, 7 days a week (period 2), compared with
      that for 2008, when the medical emergency team functioned 12 hours a day, 7 days
      a week (period 1). The commonest cause of medical emergency team activation was
      respiratory distress (43.6%), and the medical emergency team performed early goal
      directed therapy (21.3%), respiratory care (19.9%), and difficult airway
      management (12.3%). For patients on general wards, 51.3% (period 1) and 38.4%
      (period 2) of medical emergency team activations were triggered by the electronic
      medical record-based screening system (electronic medical record-triggered
      group). In 23.4%, activation occurred because of an abnormality in laboratory
      screening criteria. The commonest activation criterion from electronic medical
      record-based screening was respiratory rate (39.4%). Over half the patients were
      treated in the general ward, and one third of the patients were transferred to
      the ICU. The electronic medical record-triggered group had lower ICU admission
      with an odds ratio of 0.35 (95% CI, 0.22-0.55). In surgical patients, the
      electronic medical record-triggered group showed the lower 28-day mortality
      (10.5%) compared with the call-triggered group (26.7%) or the double-triggered
      group (33.3%) (odds ratio 0.365 with 95% CI, 0.154-0.867, p = 0.022).
      CONCLUSIONS: We successful managed the medical emergency team with electronic
      medical record-based screening criteria and a skilled intervention team. The
      electronic medical record-triggered group had lower ICU admission than the call
      triggered group or the double-triggered group. In surgical patients, the
      electronic medical record-triggered group showed better outcome than other
      groups.

PMID- 24335441
TI  - An international career development survey of critical care practitioners*.
AB  - OBJECTIVES: To understand the career development needs of an international
      multidisciplinary group of critical care practitioners in the 21st century.
      DESIGN: A web-accessible survey deployed by the In-Training Section of the
      Society of Critical Care Medicine. SETTING: University health sciences center.
      SUBJECTS: Physicians (doctor of medicine and doctor of osteopathic medicine),
      advance practice providers (nurse practitioner, physician assistant, nurses,
      pharmacists, and student members of the Society of Critical Care Medicine.
      INTERVENTIONS: The survey covered domains of demographics, opinions about career
      development, and opinions about the Society of Critical Care Medicine In-Training
      Section. MEASUREMENTS AND MAIN RESULTS: One thousand forty-nine of approximately
      16,000 Society of Critical Care Medicine members responded to the survey (7%
      response rate). Continuing education (280, 26.7%), leadership skills (197,
      18.8%), and scientific development (192, 18.3%) are among the most important
      issues for the respondents. Many critical care practitioners would like to assist
      Society of Critical Care Medicine's efforts in career development (948, 90.4%)
      and many would consider some aspect of committee involvement (796, 75.9%). The
      Society of Critical Care Medicine In-Training Section, whose primary mission is
      career development across the spectrum of providers and expertise levels, needs
      improved advertisement (981, 93.7%). There is strong support for upcoming Annual
      Congresses dedicated to career development (834, 79.5%). Of the three main
      methods of information dissemination for Society of Critical Care Medicine career
      development initiatives from the In-Training Section, respondents rank e-mail
      highest (762, 72.6%), followed by webpages (228, 21.7%) and I-rooms (59, 5.6%).
      Over half of the Society of Critical Care Medicine membership surveyed lack a
      career development mentor in critical care. CONCLUSIONS: This is the largest
      assessment of the international critical care community regarding the career
      development needs of 21st century critical care practitioner although the limited
      response rate makes this work prone to sampling bias. Career development issues
      are broad and in need of further development by the Society of Critical Care
      Medicine In-Training Section. Although these initiatives need improved marketing,
      the Society of Critical Care Medicine membership is willing to help support them
      and work to further shape them in the future.

PMID- 24335440
TI  - FTY720 (s)-phosphonate preserves sphingosine 1-phosphate receptor 1 expression
      and exhibits superior barrier protection to FTY720 in acute lung injury.
AB  - OBJECTIVE: Effective therapies are needed to reverse the increased vascular
      permeability that characterizes acute inflammatory diseases such as acute lung
      injury. FTY720 is a pharmaceutical analog of the potent barrier-enhancing
      phospholipid, sphingosine 1-phosphate. Because both FTY720 and sphingosine 1
      phosphate have properties that may limit their usefulness in patients with acute
      lung injury, alternative compounds are needed for therapeutic use. The objective
      of this study is to characterize the effects of FTY720 (S)-phosphonate, a novel
      analog of FTY720-phosphate, on variables of pulmonary vascular permeability in
      vitro and alveolar-capillary permeability in vivo. SETTING: University-affiliated
      research institute. SUBJECTS: Cultured human pulmonary endothelial cells; C57BL/6
      mice. INTERVENTIONS: Endothelial cells were stimulated with sphingosine 1
      phosphate receptor 1 agonists to determine effects on sphingosine 1-phosphate
      receptor 1 expression. Acute lung injury was induced in C57BL/6 mice with
      bleomycin to assess effects of sphingosine 1-phosphate receptor 1 agonists.
      MEASUREMENTS AND MAIN RESULTS: FTY720 (S)-phosphonate potently increases human
      pulmonary endothelial cell barrier function in vitro as measured by
      transendothelial electrical resistance. Reduction of sphingosine 1-phosphate
      receptor 1 with small interference RNA significantly attenuates this
      transendothelial electrical resistance elevation. FTY720 (S)-phosphonate
      maintains endothelial sphingosine 1-phosphate receptor 1 protein expression in
      contrast to greater than 50% reduction after incubation with sphingosine 1
      phosphate, FTY720, or other sphingosine 1-phosphate receptor 1 agonists. FTY720
      (S)-phosphonate does not induce beta-arrestin recruitment, sphingosine 1
      phosphate receptor 1 ubiquitination, and proteosomal degradation that occur after
      other agonists. Intraperitoneal administration of FTY720 (S)-phosphonate every
      other day for 1 week in normal or bleomycin-injured mice maintains significantly
      higher lung sphingosine 1-phosphate receptor 1 expression compared with FTY720.
      FTY720 fails to protect against bleomycin-induced acute lung injury in mice,
      while FTY720 (S)-phosphonate significantly decreases lung leak and inflammation.
      CONCLUSION: FTY720 (S)-phosphonate is a promising barrier-promoting agent that
      effectively maintains sphingosine 1-phosphate receptor 1 levels and improves
      outcomes in the bleomycin model of acute lung injury.

PMID- 24335442
TI  - Increased ICU resource needs for an academic emergency general surgery service*.
AB  - OBJECTIVE: ICU needs of nontrauma emergency general surgery patients are poorly
      described. This study was designed to compare ICU utilization of emergency
      general surgery patients admitted to an acute care emergency surgery service with
      other general surgery patients. Our hypothesis is that tertiary care emergency
      general surgery patients utilize more ICU resources than other general surgical
      patients. DESIGN: Retrospective database review. SETTING: Academic, tertiary
      care, nontrauma surgical ICU. PATIENTS: All patients admitted to the surgical ICU
      over age 18 between March 2004 and June 2012. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Six thousand ninety-eight patients were evaluated: 1,053 acute
      care emergency surgery, 1,964 general surgery, 1,491 transplant surgery, 995
      facial surgery/otolaryngology, and 595 neurosurgery. Acute care emergency surgery
      patients had statistically significantly longer ICU lengths of stay than other
      groups: acute care emergency surgery (13.5 +/- 17.4 d) versus general surgery
      (8.7 +/- 12.9), transplant (7.8 +/- 11.6), oral-maxillofacial surgery (5.5 +/-
      4.2), and neurosurgery (4.47 +/- 9.8) (all p< 0.01). Ventilator usage, defined by
      percentage of total ICU days patients required mechanical ventilation, was
      significantly higher for acute care emergency surgery patients: acute care
      emergency surgery 73.4% versus general surgery 64.9%, transplant 63.3%, oral
      maxillofacial surgery 58.4%, and neurosurgery 53.1% (all p < 0.01). Continuous
      renal replacement therapy usage, defined as percent of patients requiring this
      service, was significantly higher in acute care emergency surgery patients: acute
      care emergency surgery 10.8% versus general surgery 4.3%, transplant 6.6%, oral
      maxillofacial surgery 0%, and neurosurgery 0.5% (all p < 0.01). Acute care
      emergency surgery patients were more likely interhospital transfers for tertiary
      care services than general surgery or transplant (24.5% vs 15.5% and 8.3%
      respectively, p < 0.001 for each) and more likely required emergent surgery
      (13.7% vs 6.7% and 3.5%, all p < 0.001). Chronic comorbidities were similar
      between acute care emergency surgery and general surgery, whereas transplant had
      fewer. CONCLUSIONS: Emergency general surgery patients have increased ICU needs
      in terms of length of stay, ventilator usage, and continuous renal replacement
      therapy usage compared with other services, perhaps due to the higher percentage
      of transfers and emergent surgery required. These patients represent a distinct
      population. Understanding their resource needs will allow for better deployment
      of hospital resources.

PMID- 24335443
TI  - Liberal versus restricted fluid resuscitation strategies in trauma patients: a
      systematic review and meta-analysis of randomized controlled trials and
      observational studies*.
AB  - OBJECTIVE: Hemorrhage is responsible for most deaths that occur during the first
      few hours after trauma. Animal models of trauma have shown that restricting fluid
      administration can reduce the risk of death; however, studies in patients are
      difficult to conduct due to logistical and ethical problems. To maximize the
      value of the existing evidence, we performed a meta-analysis to compare liberal
      versus restricted fluid resuscitation strategies in trauma patients. DATA
      SOURCES: Medline and Embase were systemically searched from inception to February
      2013. STUDY SELECTION: We selected randomized controlled trials and observational
      studies that compared different fluid administration strategies in trauma
      patients. There were no restrictions for language, population, or publication
      year. DATA EXTRACTION: Four randomized controlled trials and seven observational
      studies were identified from 1,106 references. One of the randomized controlled
      trials suffered from a high protocol violation rate and was excluded from the
      final analysis. DATA SYNTHESIS: The quantitative synthesis indicated that liberal
      fluid resuscitation strategies might be associated with higher mortality than
      restricted fluid strategies, both in randomized controlled trials (risk ratio,
      1.25; 95% CI, 1.01-1.55; three trials; I(2), 0) and observational studies (odds
      ratio, 1.14; 95% CI, 1.01-1.28; seven studies; I(2), 21.4%). When only adjusted
      odds ratios were pooled for observational studies, odds for mortality with
      liberal fluid resuscitation strategies increased (odds ratio, 1.19; 95% CI, 1.02
      1.38; six studies; I(2), 26.3%). CONCLUSIONS: Current evidence indicates that
      initial liberal fluid resuscitation strategies may be associated with higher
      mortality in injured patients. However, available studies are subject to a high
      risk of selection bias and clinical heterogeneity. This result should be
      interpreted with great caution.

PMID- 24335444
TI  - Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte
      solution on acute kidney injury in a rat model of sepsis*.
AB  - OBJECTIVE: To compare the acute effects of 0.9% saline versus a balanced
      electrolyte solution on acute kidney injury in a rat model of sepsis. DESIGN:
      Controlled laboratory experiment. SETTING: University laboratory. SUBJECTS: Sixty
      adult, male Sprague-Dawley rats. INTERVENTIONS: We induced sepsis by cecal
      ligation and puncture and randomized animals to receive fluid resuscitation with
      either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal
      ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr).
      Blood and urine specimens were obtained from baseline, 18 hours after cecal
      ligation and puncture, immediately after 4 hours fluid resuscitation, and 24
      hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin
      6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We
      also analyzed urine for cystatin C and neutrophil gelatinase-associated
      lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for
      creatinine to assess severity of acute kidney injury. We observed all animals for
      survival up to 1 day after resuscitation. Surviving animals were killed for
      kidney histology. Finally, we carried out an identical study in 12 healthy
      animals. MEASUREMENTS AND MAIN RESULTS: Compared with Plasma-Lyte, 0.9% saline
      resuscitation resulted in significantly greater blood chloride concentrations (p
      < 0.05) and significantly decreased pH and base excess. Acute kidney injury
      severity measured by RIFLE criteria was increased with 0.9% saline compared with
      Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with
      kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival
      favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy
      animals, we found no differences between fluids and no evidence of acute kidney
      injury. CONCLUSION: Volume resuscitation with Plasma-Lyte resulted in less
      acidosis and less kidney injury and improved short-term survival when compared
      with 0.9% saline in this experimental animal model of sepsis.

PMID- 24335445
TI  - Evaluating the efficacy and safety of two doses of the polyclonal anti-tumor
      necrosis factor-alpha fragment antibody AZD9773 in adult patients with severe
      sepsis and/or septic shock: randomized, double-blind, placebo-controlled phase
      IIb study*.
AB  - OBJECTIVE: This trial compared the efficacy/safety of two IV doses of AZD9773, a
      polyclonal antibody to tumor necrosis factor-alpha, in adult patients with severe
      sepsis/septic shock. DESIGN: Multicenter, randomized, double-blind, placebo
      controlled phase IIb trial. SETTING: ICUs in seven countries (Australia, Belgium,
      Canada, Czech Republic, Finland, France, and Spain). PATIENTS: Patients 18 years
      old or older with severe sepsis and/or septic shock. Patients were required to
      have 1) objective clinical evidence of infection; 2) at least two of four
      systemic inflammatory response syndrome criteria; and 3) cardiovascular and/or
      respiratory sepsis-related failure. INTERVENTIONS: Patients were randomized 1:1:1
      to a single loading infusion of AZD9773 250 U/kg followed by 50 U/kg every 12
      hours (low dose, n = 100), a single loading infusion of AZD9773 500 U/kg followed
      by 100 U/kg every 12 hours (high dose, n = 100), or placebo (n = 100) for 5 days.
      Follow-up assessments were performed up to day 90. MEASUREMENTS AND MAIN RESULTS:
      Mean number of ventilator-free days (primary endpoint) did not differ between low
      dose (19.7 d) or high-dose AZD9773 (17.3 d) and placebo (18.3 d) (one-sided p =
      0.18 and 0.74, respectively). Mortality rates were comparable across treatment
      groups; relative risk of death versus placebo at day 29 was 0.80 for low-dose
      AZD9773 (one-sided p = 0.25) and 1.64 for high-dose AZD9773 (p = 0.97). Most
      patients experienced at least one treatment-emergent adverse event (87.8% in
      AZD9773-treated patients, 92.9% in placebo patients) although most were
      mild/moderate in nature. No differences in the incidence of adverse events or
      laboratory or vital sign abnormalities were observed between groups. CONCLUSIONS:
      AZD9773 rapidly and efficiently decreased plasma tumor necrosis factor-alpha
      concentration in patients with severe sepsis/septic shock, but this effect did
      not translate into clinical benefit.

PMID- 24335446
TI  - Family presence during brain death evaluation: a randomized controlled trial*.
AB  - OBJECTIVE: To evaluate if a family presence educational intervention during brain
      death evaluation improves understanding of brain death without affecting
      psychological distress. DESIGN: Randomized controlled trial. SETTING: Four ICUs
      at an academic tertiary care center. SUBJECTS: Immediate family members of
      patients suspected to have suffered brain death. INTERVENTIONS: Subjects were
      group randomized to presence or absence at bedside throughout the brain death
      evaluation with a trained chaperone. All randomized subjects were administered a
      validated "understanding brain death" survey before and after the intervention.
      Subjects were assessed for psychological well-being between 30 and 90 days after
      the intervention. MEASUREMENTS AND MAIN RESULTS: Follow-up assessment of
      psychological well-being was performed using the Impact of Event Scale and
      General Health Questionnaire. Brain death understanding, Impact of Event Scale,
      and General Health Questionnaire scores were analyzed using Wilcoxon
      nonparametric tests. Analyses were adjusted for within family correlation. Fifty
      eight family members of 17 patients undergoing brain death evaluation were
      enrolled: 38 family members were present for 11 brain death evaluations and 20
      family members were absent for six brain death evaluations. Baseline
      understanding scores were similar between groups (median 3.0 [presence group] vs
      2.5 [control], p = 0.482). Scores increased by a median of 2 (interquartile
      range, 1-2) if present versus 0 (interquartile range, 0-0) if absent (p < 0.001).
      Sixty-six percent of those in the intervention group achieved perfect
      postintervention "understanding" scores, compared with 20% of subjects who were
      not present (p = 0.02). Median Impact of Event Scale and General Health
      Questionnaire scores were similar between groups at follow-up (Impact of Event
      Scale: present = 20.5, absent = 23.5, p = 0.211; General Health Questionnaire:
      present = 13.5, absent = 13.0, p = 0.250). CONCLUSIONS: Family presence during
      brain death evaluation improves understanding of brain death with no apparent
      adverse impact on psychological well-being. Family presence during brain death
      evaluation is feasible and safe.

PMID- 24335447
TI  - A multibiomarker-based outcome risk stratification model for adult septic shock*.
AB  - OBJECTIVES: Clinical trials in septic shock continue to fail due, in part, to
      inequitable and sometimes unknown distribution of baseline mortality risk between
      study arms. Investigators advocate that interventional trials in septic shock
      require effective outcome risk stratification. We derived and tested a
      multibiomarker-based approach to estimate mortality risk in adults with septic
      shock. DESIGN: Previous genome-wide expression studies identified 12 plasma
      proteins as candidates for biomarker-based risk stratification. The current
      analysis used banked plasma samples and clinical data from existing studies.
      Biomarkers were assayed in plasma samples obtained from 341 subjects with septic
      shock within 24 hours of admission to the ICU. Classification and regression tree
      analysis was used to generate a decision tree predicting 28-day mortality based
      on a combination of both biomarkers and clinical variables. The derived tree was
      first tested in an independent cohort of 331 subjects, then calibrated using all
      subjects (n = 672), and subsequently validated in another independent cohort (n =
      209). SETTING: Multiple ICUs in Canada, Finland, and the United States. SUBJECTS:
      Eight hundred eighty-one adults with septic shock or severe sepsis. INTERVENTION:
      None. MEASUREMENTS AND MAIN RESULTS: The derived decision tree included five
      candidate biomarkers, admission lactate concentration, age, and chronic disease
      burden. In the derivation cohort, sensitivity for mortality was 94% (95% CI, 87
      97), specificity was 56% (50-63), positive predictive value was 50% (43-57), and
      negative predictive value was 95% (89-98). Performance was comparable in the test
      cohort. The calibrated decision tree had the following test characteristics in
      the validation cohort: sensitivity 85% (76-92), specificity 60% (51-69), positive
      predictive value 61% (52-70), and negative predictive value 85% (75-91).
      CONCLUSIONS: We have derived, tested, calibrated, and validated a risk
      stratification tool and found that it reliably estimates the probability of
      mortality in adults with septic shock.

PMID- 24335449
TI  - Acute liver failure associated with traditional Chinese medicine: report of 30
      cases from seven tertiary hospitals in China*.
AB  - OBJECTIVES: Up to now, limited cases with acute liver failure caused by
      traditional Chinese medicine have been reported, and thus this topic has been
      scarcely discussed. This study aims to report such cases from China. DESIGN: A
      retrospective study. SETTING: Clinical investigation among seven tertiary
      hospitals in different areas of China. PATIENTS: From January 2007 to December
      2012, patients with acute liver failure induced by traditional Chinese medicinal
      herbs were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total
      of 30 patients were finally identified, including six men and 24 women. The
      average age was 39.7 years. The median period from initial symptoms to the
      development of hepatic encephalopathy was 13 days. Nine patients (30%) had
      accepted herbal therapies due to their skin disorders before the onset of acute
      liver failure. Eighteen patients (60%) eventually died, 10 of whom died of heavy
      bleeding. No patients received liver transplantation. CONCLUSIONS: The model of
      safety monitoring for traditional Chinese materia medica should be established.
      For those critically ill patients with herb-induced acute liver failure,
      coagulopathy is a vital problem in critical care. Additionally, the rate of liver
      transplantation for acute liver failure in China needs to be improved.

PMID- 24335448
TI  - Postresuscitation administration of doxycycline preserves cardiac contractile
      function in hypoxia-reoxygenation injury of newborn piglets*.
AB  - OBJECTIVE: Cardiac injury is common in asphyxiated neonates and is associated
      with matrix metalloproteinase-2 activation. Although studies have demonstrated
      the cardioprotective effects of matrix metalloproteinase inhibition, this has not
      been tested in clinically translatable models of hypoxia-reoxygenation injury. We
      aimed to elucidate the effect of doxycycline, a matrix metalloproteinase
      inhibitor, on cardiac injury and functional recovery in a swine model of neonatal
      hypoxia-reoxygenation. DESIGN: Thirty-three newborn piglets were acutely
      instrumented for continuous monitoring of cardiac output and systemic arterial
      pressure. After stabilization, normocapnic alveolar hypoxia (10-15% oxygen) was
      instituted for 2 hours followed by 4 hours of normoxic reoxygenation. Piglets
      were blindly, block randomized to receive IV boluses of normal saline (control)
      and doxycycline at 5 minutes of reoxygenation (n = 7/group). Sham-operated
      piglets (n = 5) received no hypoxia-reoxygenation. Markers of myocardial injury
      (plasma and myocardial tissue troponin I; myocardial lactate) and oxidative
      stress (lipid hydroperoxides) were measured by enzyme-linked immunosorbent assay
      and Western blot. Myocardial matrix metalloproteinase-2 activity was quantified
      by gelatin zymography and immunoprecipitation. SETTING: University animal
      laboratory. SUBJECTS: Piglets (1-4 d old, weighing 1.4-2.5 kg). INTERVENTIONS: IV
      doxycycline (3, 10, or 30 mg/kg) given during resuscitation. MEASUREMENTS AND
      MAIN RESULTS: Hypoxic piglets had cardiogenic shock (cardiac output 58% +/- 1% of
      baseline), hypotension (systemic arterial pressure 31 +/- 1 mm Hg), and acidosis
      (pH 7.02 +/- 0.02). Doxycycline improved cardiac and stroke volume index with no
      chronotropic effect in doxycycline-treated piglets compared with controls.
      Systemic arterial pressure was higher and the pulmonary artery pressure/systemic
      arterial pressure ratio was lower in doxycycline groups, with reduced levels of
      markers of myocardial injury and oxidative stress in doxycycline-treated piglets
      compared with controls. Negative correlations were found between markers of
      myocardial injury (plasma troponin I, myocardial lactate) and functional recovery
      and between myocardial tissue and plasma troponin I. Doxycycline-treated piglets
      had lower myocardial matrix metalloproteinase-2 activity compared with controls.
      CONCLUSIONS: Postresuscitation administration of doxycycline attenuates cardiac
      injury and improves functional recovery in newborn piglets with hypoxia
      reoxygenation.

PMID- 24335450
TI  - Compliance factors associated with contact lens-related dry eye.
AB  - OBJECTIVE: To determine if compliance factors are associated with contact lens
      related dry eye (CLDE). METHODS: The data were derived from subject responses to
      a compliance survey administered in a cross-sectional study including 100
      healthy, daily (nonovernight), experienced soft contact lens wearers (50 normal
      and 50 with CLDE). Classification into normal or CLDE groups was based on Contact
      Lens Dry Eye Questionnaire scores, tear breakup time, and 2 hours difference
      between total and comfortable daily lens wear hours. The compliance survey
      queried aspects of lens care, rub and rinse practices, lens and lens case
      replacement frequency, solution replacement, and sleeping with lenses.
      Statistical analysis of the data was performed using unpaired T tests, chi, and
      Fisher exact tests as applicable. RESULTS: The average age of all subjects was
      24.8+/-4.4 years, and 60% were women. Overall compliance rates were low for
      several variables including recommended replacement of contact lenses (53%), rub
      and rinse practices (69% and 45%, respectively), care solution topping-off (80%),
      and washing hands before handling lenses (48%). However, almost no compliance
      factors were associated with CLDE status, with the exception of perceived ease or
      difficulty with lens care, which was rated as more difficult by the CLDE group
      (P=0.004). CONCLUSIONS: Overall compliance rates with contact lens care practices
      are very low, highlighting the need for more effective methods of patient
      education regarding contact lens care and compliance. However, almost no
      compliance factors were found to be associated with CLDE. Factors other than
      compliance likely play a bigger role in CLDE.

PMID- 24335451
TI  - Comparison of tear film surface quality measured in vivo on water gradient
      silicone hydrogel and hydrogel contact lenses.
AB  - OBJECTIVE: Recently, a new water gradient silicone hydrogel material has been
      introduced for a daily disposable lens. The aim of this study was to assess, in
      vivo, the prelens tear film surface quality (TFSQ) of this new lens in comparison
      with that of another daily disposable lens from the same manufacturer. METHODS:
      Eleven subjects wore two pairs of hydrogel nelfilcon A and silicone hydrogel
      delefilcon A lenses in two nonconsecutive days. The noninvasive lateral shearing
      interferometry was used to analyze the prelens tear film and distinguish between
      different contact lens materials. Measurements were taken in natural blinking
      conditions after 6 hours of wear. Additionally, the subjective comfort was
      evaluated. RESULTS: The presence of both lenses resulted in a TFSQ reduction as
      compared with the bare eye condition. Statistically significant (Wilcoxon rank
      sum test, P<0.012) smaller change in TFSQ was introduced by the water gradient
      material than the high water content material. A statistically significant
      correlation between the TFSQ results of the two lenses was found (Pearson
      correlation coefficient R=0.8, P<0.003), indicating high linearity of the
      measurement methodology with respect to the tested lens material. The correlation
      of subjective comfort in lenses was lower and found to be insignificant (R=0.6,
      P>0.05). CONCLUSIONS: Although the prelens TFSQ is not always directly
      proportional to the lens water content, the results of the in vivo study showed
      that the new water gradient silicone hydrogel material impact less TFSQ as
      compared with its predecessor.

PMID- 24335452
TI  - Changes in ultraviolet transmittance of hydrogel and silicone-hydrogel contact
      lenses induced by wear.
AB  - OBJECTIVES: To evaluate the ultraviolet (UV) transmittance spectra of different
      contact lenses and assess the effect of wear on UV transmittance values and
      ocular protection factor (PF). METHODS: Transmittance in the UV range (200-400
      nm) of 216 contact lenses was measured before and after wear, using a
      spectrophotometer. The contact lenses used were ACUVUE TruEye, ACUVUE MOIST,
      ACUVUE OASYS, ACUVUE 2, ACUVUE DEFINE, DAILIES AquaComfort Plus, AIR OPTIX for
      astigmatism, FreshLook ONE-DAY lens, and Neo Cosmo. RESULTS: This study indicates
      that the following contact lenses transmitted less than the American National
      Standards Institute (ANSI) of 5% or less of UVB: ACUVUE DEFINE, ACUVUE MOIST,
      ACUVUE 2, ACUVUE TruEye, and ACUVUE OASYS. All lenses also met the ANSI standard
      of less than 30% transmittance of UVA except for AquaComfort Plus, AIR OPTIX for
      astigmatism, and Neo Cosmo. FreshLook meets the UVA transmission standard but
      fell short of the UVB transmission standard by 3%. FreshLook and ACUVUE MOIST had
      the highest calculated PF (3.9) of the hydrogel group and were unaffected after
      wear. Of the silicone-hydrogels (SiHs), the PF for AIR OPTIX for astigmatism was
      the highest (10.6) before wear and increased after wear to a PF of 13.3. The
      results also show that, for the UVC region, significant differences exist in
      transmittance values before and after wear of all SiH lenses and all hydrogel
      lenses, except for Neo Cosmo. FreshLook and Neo Cosmo were the only lenses that
      showed no statistically significant differences in the UVA transmittance after
      wear. CONCLUSIONS: Ultraviolet-blocking contact lenses were effective in blocking
      ultraviolet radiation to safe levels recommended by ANSI, whereas non-UV blockers
      such as AquaComfort Plus and AIR OPTIX for astigmatism also showed UV-attenuation
      capabilities greater than the values previously reported. The Neo Cosmo contact
      lens transmitted greater than 86% UVB and 89% UVA, making it unsuitable for UV
      protection seekers. Transmission is modified after contact lens wear in almost
      all lenses but more so in the SiH lenses, probably because of the formation of
      biofilms on the lens surface.

PMID- 24335453
TI  - Fully automated biometry of in situ intraocular lenses using long scan depth
      spectral-domain optical coherence tomography.
AB  - PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) was used to
      automatically measure accommodative biometric changes in the anterior segment of
      eyes implanted with an intraocular lens (IOL). The repeatability and reliability
      of the automated measurements were also evaluated. METHODS: Long scan depth SD
      OCT was used to image the anterior segment of eyes implanted with IOLs. A fully
      automated algorithm was used to detect the boundaries of the cornea and IOL and
      yielded the measurements. The results included anterior segment dimensions in IOL
      eyes and the deflection of the IOLs. Automated measurements were validated in
      vitro and compared with the manual results in vivo on 15 cross-sectional images
      from patients with IOLs. Five eyes with five different types of IOLs,
      respectively, were enrolled to test the repeatability of the automated
      measurements during accommodation. RESULTS: Intraocular lens central thickness
      and anterior and posterior curvature radii measured by long scan depth SD-OCT in
      vitro and in a model eye matched well with those determined by a micrometer
      caliper and interferometer. In vivo, there was good correlation of the biometric
      data determined by automated and manual segmentations (P<0.05, r-value range:
      0.635-0.997). There were no significant differences for any variable between the
      two measurements at each accommodative state (P>0.05). Anterior chamber depth and
      pupil diameter showed significant changes between the nonaccommodative and 2.5-D
      accommodative states (P<0.05), whereas the shape of the IOLs did not change
      significantly (P>0.05). CONCLUSIONS: The long scan depth SD-OCT with the
      automated algorithm was verified to have a great potential in studying
      accommodative biometric changes of the anterior segment in eyes with IOLs and IOL
      deflections.

PMID- 24335454
TI  - Efficacy of intralesional bevacizumab administration in primary pterygium: a
      quantitative analysis.
AB  - OBJECTIVE: To analyze the regression of the pterygium tissue quantitatively after
      intralesional bevacizumab administration in patients with primary pterygium.
      METHODS: Thirty-three eyes of 33 patients with primary pterygium who underwent
      intralesional bevacizumab (1.25 mg per 0.05 mL) administration were included in
      this prospective study. The ocular irritation, best-corrected visual acuity
      (BCVA), slit-lamp and funduscopic examinations, corneal astigmatism, the
      horizontal length, and the thickness of the pterygium were assessed before and
      after 2 months of treatment. To evaluate the corneal astigmatism and the
      thickness of the pterygium, the Pentacam comprehensive eye scanner (Pentacam CES;
      Oculus GmbH) was used. RESULTS: After 2 months of bevacizumab administration, the
      average BCVA was improved (P=0.003). The average ocular irritation score,
      horizontal length, and the thickness of the pterygium were statistically
      significantly decreased (P<0.001, P<0.001, P<0.001, respectively). CONCLUSION:
      After 2 months of intralesional bevacizumab administration, the average amount of
      decrease in the horizontal length and thickness of the pterygium was 0.6 mm and
      37 MUm, respectively. Intralesional bevacizumab administration is useful in the
      management of primary pterygium without having any local or systemic adverse
      effects; however, repeated administrations are needed to provide clinically more
      significant results.

PMID- 24335455
TI  - [Recurrent tuberculosis: relapse or reinfection?].
AB  - Recurrent tuberculosis (TB) is an issue that makes worldwide eradication of the
      disease difficult, especially in countries with a high incidence of TB. Recurrent
      TB may be due to relapse of the original episode or to an exogenous reinfection
      caused by a different strain of Mycobacterium tuberculosis. We performed a meta
      analysis of selected studies on recurrent TB from 2000 to 2013, adopting
      molecular genotyping to discriminate between exogenous reinfection and relapses,
      in order to specifically evaluate the role of HIV infection in the origin of
      recurrence. Comparison among the studies was limited by the population
      heterogeneity of the different studies in terms of epidemiology, health status,
      and diagnostic and therapeutic approach. However, exogenous reinfections are more
      common in high-burden countries, where HIV infection plays a major role in
      increasing the risk of a new infection. In contrast, this finding was not
      confirmed in low-burden countries. Vice versa, globally recognized factors for TB
      relapse were low compliance to anti-tuberculous treatment, multidrug resistance
      and persistence of cavitations in the lung parenchyma. The role of other factors
      like social conditions (immigration, homelessness, working conditions), co
      morbidities (silicosis), and characteristics of anti-TB treatment is still
      controversial. 

PMID- 24335456
TI  - Annual report on norovirus in children with acute gastroenteritis in 2009 and
      their genotypes in Turkey.
AB  - In order to determine the incidence, seasonal distribution and clinical
      characteristics of norovirus in children and analyse the genogroups of norovirus,
      immunochromatography was used to detect the virus in stool samples. Randomly
      selected subsets of samples were analysed for genogroups with a multiplex
      polymerase chain reaction method. Seasonal distribution of norovirus, symptoms,
      physical and laboratory findings of patients and treatment models were evaluated
      retrospectively in 2009. In all, norovirus was examined in 520 stool samples. The
      infection rate was 9.6% (50/520) among patients of acute gastroenteritis in 2009.
      The virus was mostly detected in the first 24 months of life (50%).
      Gastroenteritis with norovirus was most frequently found in February, May, July
      and September. The main symptoms were diarrhoea (100%) and vomiting (95.5%). In
      some patients affected by norovirus infection higher urine density, ketonuria and
      high CRP levels were observed. Antiemetic drugs and intravenous fluid-electrolyte
      therapy were given to 37 (84%) and 26 (59%) of patients, respectively.
      Hospitalisation was required in 11 patients (25%). All the randomly selected 28
      samples (100%) had norovirus genogroup II. In conclusion, norovirus (genogroup
      II) mostly affected children in the first two years of life and was more
      frequently observed in February, May, July and September of 2009. Diarrhoea and
      vomiting were the most frequent symptoms. Antiemetic drugs, intravenous fluid
      electrolyte therapy and hospitalisation were usually required in these patients. 

PMID- 24335457
TI  - Early discharge of infectious disease patients: an opportunity or extra cost for
      the Italian Healthcare System?
AB  - In order to assess the economic benefits of an early discharge (ED) programme for
      patients with complicated skin and soft tissue infections (cSSTIs) in terms of
      hospital and regional authority costs, an economic analysis was conducted
      comparing two possible alternatives: standard hospital management vs. an ED
      strategy followed by a period of outpatient management. Utilization of resources
      and costs were derived from the literature and expert panel evaluation. Patients
      were classified into four groups: low-intensity non-walking (LINW), low-intensity
      walking (LIW), high-intensity non-walking (HINW) and high-intensity walking
      (HIW). The overall costs (inpatient/outpatient) of hospitalization with ED for
      cSSTIs range from Euros 2,079 for LIW to Euros 2,193 for HINW, with the most
      expensive regimen (HINW) being 50% lower than the costs for 12.6 days of
      hospitalization alone (Euros 4,619). The weighted average Diagnosis Related Group
      (DRG) reimbursement for cSSTIs (Euros 2,042) does not cover the costs of such
      hospitalization. In conclusion, when a patient's conditions allow for early
      discharge there is an economic advantage for the hospital with an outpatient
      management plan, especially for patients requiring low-intensity care. However,
      this could be disadvantageous in terms of regional costs if outpatient management
      has to be paid in addition to payment by the DRG. 

PMID- 24335458
TI  - Tuberculosis deaths in a tertiary hospital in Goiania, Brazil: a descriptive
      study.
AB  - Tuberculosis (TB) remains a serious global public health problem, being the main
      cause of death in patients with AIDS, and the third cause of death by infectious
      diseases throughout the world. This is somewhat surprising because TB is a
      disease that, if treated properly, displays high rates of healing. It is
      therefore important to characterise these patients to identify target populations
      for specific measures seeking to reduce TB deaths. We performed a retrospective
      descriptive study to analyse the cases of TB deaths in a State public hospital, a
      point of reference for treatment of infectious diseases, located in the Central
      West region of Brazil, in the period from January 1st, 2008 to December 31st,
      2009. There were 283 diagnosed and reported cases of TB between 2008 and 2009,
      and 39 recorded deaths occurred, resulting in a lethality index of 14%. The mean
      age of TB patients was 42 years, and the median age 37 years. Pulmonary TB was
      the most common form of TB (51.3% of the patients). Of the 39 TB patients who
      died, 56.4% (n = 22) were co-infected with HIV. The main immediate causes of
      death were acute respiratory failure (n = 12) and sepsis (n = 8). Anaemia and
      hypoalbuminaemia were prevalent in this group, and 27 patients required
      mechanical ventilation. This study found that hospitalized patients who died had
      the following characteristics: bilateral pulmonary disease, low levels of
      haemoglobin and haematocrit, albumin, and those co-infected with HIV that were
      admitted to the ICU required MV. Prospective studies aiming to analyse the risk
      factors for death from TB are needed to better understand this process. 

PMID- 24335459
TI  - In vitro and in vivo effects of sub-MICs of pexiganan and imipenem on Pseudomonas
      aeruginosa adhesion and biofilm development.
AB  - An in vitro and in vivo study was performed to quantify adhesion and biofilm
      formation ability of Pseudomonas aeruginosa slime producer under the effect of
      sub-minimal inhibitory concentrations (MICs) of pexiganan and imipenem. To
      evaluate adherence, squares of ureteral stents were placed in six-well tissue
      culture plates containing 6 ml of a cell suspension grown in the presence of sub
      MICs of study antibiotics. To evaluate biofilm formation sterilized squares were
      placed in six-well tissue culture plates containing 6 ml of triptic soy broth
      (TSB) supplemented with 0.25% of glucose and the respective amount of antibiotic.
      For in vivo study a biofilm infection rat model was performed. The study included
      an uninfected control group to evaluate the sterility of surgical procedure, a
      group infected with a slime-producer P. aeruginosa strain not previously treated
      with antibiotics and two groups infected with the strain previously treated with
      imipenem or pexiganan. Adherence and biofilm in vitro formation was strongly
      affected by pre-treatment with pexiganan and imipenem, with the latter being the
      more effective antibiotic. The in vivo results showed a reduction in bacterial
      load on the ureteral stent tissue of the pre-treated strain. Differently, urine
      cultures showed no differences in bacterial growth for the pre-treated strain
      showing that it retained its ability to cause infection. This study suggests that
      sub-MIC imipenem and pexiganan could be a good strategy to target the adhesion
      process during the infection cycle. 

PMID- 24335460
TI  - Absence of occult HCV infection in patients experiencing an immunodepression
      condition.
AB  - The aim of our study was to evaluate the presence of occult HCV infection in two
      settings of patients experiencing immunosuppression: patients with Human
      Immunodeficiency Virus (HIV) infection and those with onco-haematological
      disease. Sixty consecutive HIV-positive/anti-HCV-negative/HCV RNA-negative
      patients (HIV group) and 32 consecutive anti-HCV/HCV RNA negative patients with
      an onco-haematological disease first undergoing chemotherapy (Onco-haematological
      group) were enrolled. HCV-RNA was sought by real time RT-PCR in plasma and
      Peripheral Blood Mononuclear Cell (PBMC) samples obtained at enrolment and during
      follow-up, in the patients in the HIV group every three months and in those in
      the onco-haematological group at months 1 and 3 during chemotherapy and then
      every three months after treatment discontinuation. No plasma or PBMC sample
      collected at enrolment and during the follow-up in the HIV and onco
      haematological groups was HCV RNA positive. The results of this study rule out
      the existence of occult HCV infection in patients with strong immunosuppression
      due to different conditions, HIV infection and onco-haematological diseases. 

PMID- 24335461
TI  - [A particular case of tubercular pneumonia].
AB  - A 50 year old woman was seen for fever and persistent cough, with elevated
      phlogosis markers and a cavitary lesion at the right upper pulmonary lobe at
      thoracic CT. Even in the absence of any culture-positive finding, but given the
      strong suspicion of tubercular disease, the patient was treated with standard
      antitubercular quadruple therapy for two months (isoniazid, pyrazinamide,
      rifampin and ethambutol) and later with two-drug therapy (isoniazid and
      rifampin). One month after the beginning of this second regimen we observed
      clinical relapse and a rise in phlogosis markers. We supposed partial resistance
      to therapy and, without any antibiogram, we decided to introduce therapy with
      oral levofloxacin (stopped for polyneuropathy) and then oral linezolid. At the
      end of therapy we observed complete clinical and radiological healing. In our
      opinion this clinical case shows clearly the diagnostic and therapeutic issues of
      the tubercular disease: the need to start therapy even in the absence of positive
      cultures, the presence of resistance to conventional therapy and the possibility
      of alternative therapeutic regimes with oral antibiotics. 

PMID- 24335462
TI  - Vacuum-assisted therapy accelerates wound healing in necrotizing soft tissue
      infections: our experience in two intravenous drug abuse patients.
AB  - Negative pressure wound therapy using vacuum-assisted closure (VAC) devices is
      currently a well established technique for managing complicated wounds. Such
      wounds occur after aggressive surgical debridement for necrotizing soft tissue
      infections (NSTI). In this report we present our experience in two intravenous
      drug abusers managed with VAC for NSTIs. The patients were 25 and 34 years old,
      HCV positive and presented with oedema of the upper femoral compartments and
      concomitant severe sepsis. Ultrasonography and computed tomography revealed
      severe cellulitis, fluid collection and necrosis of the affected fasciae and
      muscles. After emergent and subsequent aggressive surgical debridement during the
      first 48h, the VAC device was applied. Both patients had an uncomplicated
      postoperative course and a fast recovery from their multiorgan dysfunction.
      Suture closure of the wounds was achieved at the 25th and 38th postoperative days
      respectively and patients were discharged without any motor deficit. Negative
      pressure wound therapy is a modern therapeutic modality for treating complicated
      infected wounds. Moreover, it accelerates wound healing and primary closure,
      facilitating patient ambulation and recovery. A dedicated medical and nursing
      team is an important prerequisite for a successful outcome. 

PMID- 24335463
TI  - Is Chryseobacterium indologenes a shunt-lover bacterium? A case report and review
      of the literature.
AB  - Chryseobacterium indologenes is a non-fermentative Gram-negative bacillus
      formerly belonging to the Flavobacterium genus. It is widely found in water and
      soil, also on wet surfaces of the hospital environment. It rarely causes
      infections and is usually associated with altered immune status or indwelling
      devices. We present a case of ventriculoperitoneal shunt infection caused by C.
      indologenes in a premature pediatric patient. A six-month-old male infant with
      congenital hydrocephalus and ventriculoperitoneal shunt was admitted with
      complaints of irritability, high fever and projectile vomiting. He was diagnosed
      as suffering from meningitis based on the clinical symptoms and laboratory
      findings of cerebrospinal fluid. The ventriculoperitoneal shunt was externalized
      and cerebrospinal fluid samples were sent for bacterial cultures. The isolated
      bacterium was identified as C. indologenes by conventional methods and the BD
      PhoenixTM 100 (Becton Dickinson, MD, USA) fully automated microbiology system.
      Antimicrobial susceptibility testing was performed by the microdilution method
      and Kirby-Bauer's disk diffusion method according to the Clinical and Laboratory
      Standards Institute guidelines. The isolate was found susceptible to
      ciprofloxacin, levofloxacin, cefoperazone and trimethoprim-sulfamethoxazole,
      while it was resistant to amikacin, aztreonam, cefepime, ceftazidime, gentamicin,
      imipenem and ticarcillin-clavulanic acid. The treatment was started with
      trimethoprim-sulfamethoxazole and cefoperazone-sulbactam The ventriculoperitoneal
      shunt was then removed. The patient was fully healed after two weeks and
      discharged. Central nervous system infection is a rare form of C. indologenes
      infections. The case presented herein may make a useful contribution to the
      existing literature.

PMID- 24335464
TI  - Hallmarks in history of syphilis therapeutics.
AB  - At the end of the 15th century syphilis appeared in Europe as a devastating
      epidemic. For nearly four centuries mercury was regarded as a remedy of first
      rate importance along with guaiac and potassium iodide. In the early 20th
      century, two new substances were added to syphilis therapeutics, namely
      arsenobenzol and bismuth. The absence of treponemal serum tests and the erroneous
      attribution of the positive Wassermann reaction exclusively to Treponema pallidum
      infection resulted in prolonged and non-proven effective treatments. In 1943 John
      Mahoney introduced penicillin, revolutionizing the treatment of syphilis. 

PMID- 24335465
TI  - [The re-introduction of malaria in the Pontine Marshes and the Cassino district
      during the end of World War II. Biological warfare or global war tactics?].
AB  - After the fall of the Fascist regime on September 8, 1943, Italy was split into
      two parts: (i) the Southern regions where the King Victor Emanuel III and the
      military general staff escaped was under the control of English-American allied
      armies, and (ii) the northern regions comprising Lazio, Tuscany, Umbria, and
      Marche still under the control of the Germans. The German Wehrmacht, after
      suffering several defeats on Southern lines, established a new strengthened line
      of defence called the Gustav line, located south of Rome and crossing in the
      western portion the recently-drained Pontine Marshes. In his book published in
      2006, Frank Snowden hypothesised that occupying German armies in 1943 had
      initiated a programme of re-flooding the Pontine plain as a biological warfare
      strategy to re-introduce malaria infection in the territories south of Rome, Such
      a plan was intended (i) to slow down the advance of English-American forces, and
      (ii) to punish Italians who abandoned their former allies. Other authors,
      including Annibale Folchi, Erhard Geissler, and Jeanne Guillemin, have disputed
      this hypothesis based on an analysis of recently-uncovered archive documents.
      What is not disputed is that the flooding of the Pontine and Roman plains in 1943
      contributed to a severe malaria epidemic in 1944, which was associated with
      exceptionally high morbidity and mortality rates in the afflicted populations.
      Herein, we critically evaluate the evidence and arguments of whether the
      Wehrmacht specifically aimed to spread malaria as a novel biological warfare
      strategy in Italy during the Second World War. In our opinion, evidence for
      specific orders to deliberately spread malaria by the German army is lacking,
      although the strategy itself may have been considered by Nazis during the waning
      years of the war. 

PMID- 24335466
TI  - The role of bile salt export pump gene repression in drug-induced cholestatic
      liver toxicity.
AB  - The bile salt export pump (BSEP, ABCB11) is predominantly responsible for the
      efflux of bile salts, and disruption of BSEP function is often associated with
      altered hepatic homeostasis of bile acids and cholestatic liver injury.
      Accumulating evidence suggests that many drugs can cause cholestasis through
      interaction with hepatic transporters. To date, a relatively strong association
      between drug-induced cholestasis and attenuated BSEP activity has been proposed.
      However, whether repression of BSEP transcription would contribute to drug
      induced cholestasis is largely unknown. In this study, we selected 30 drugs
      previously reported as BSEP inhibitors to evaluate their effects on BSEP
      expression, farnesoid X receptor (FXR) activation, and correlations to clinically
      reported liver toxicity. Our results indicate that of the 30 BSEP inhibitors,
      five exhibited potent repression of BSEP expression (>=60% repression), ten were
      moderate repressors (20-60% repression), whereas others had negligible effects
      (<=20% repression). Of importance, two drugs (troglitazone and benzbromarone),
      previously withdrawn from the market because of liver injury, are among the
      potent repressors. Further investigation of the five potent repressors revealed
      that transcriptional repression of BSEP by lopinavir and troglitazone may occur
      through their interaction with FXR, whereas others are via FXR-independent yet
      unidentified pathways. Our data suggest that in addition to functional
      inhibition, repression of BSEP expression may play an important role in drug
      induced cholestatic liver toxicity. Thus, a combination of the two would reveal a
      more accurate prediction of drug-induced cholestasis than does either repression
      or inhibition alone. 

PMID- 24335467
TI  - Rapid diagnosis of sepsis.
AB  - Fast and appropriate therapy is the cornerstone in the therapy of sepsis.
      However, the discrimination of sepsis from non-infectious causes of inflammation
      may be difficult. Biomarkers have been suggested to aid physicians in this
      decision. There is currently no biochemical technique available which alone
      allows a rapid and reliable discrimination between sepsis and non-infectious
      inflammation. Procalcitonin (PCT) is currently the most investigated biomarker
      for this purpose. C-reactive protein and interleukin 6 perform inferior to PCT in
      most studies and their value in diagnosing sepsis is not defined. All biomarkers
      including PCT are also released after various non-infectious inflammatory
      impacts. This shortcoming needs to be taken into account when biomarkers are used
      to aid the physician in the diagnosis of sepsis. Polymerase chain reaction (PCR)
      based pathogen detection may improve time to adequate therapy but cannot rule out
      the presence of infection when negative. 

PMID- 24335469
TI  - Post-cardiotomy type A aortic dissection.

PMID- 24335468
TI  - Characterization of a fluorescent probe for imaging nitric oxide.
AB  - BACKGROUND: Nitric oxide (NO), a potent vasodilator and anti-atherogenic
      molecule, is synthesized in various cell types, including vascular endothelial
      cells (ECs). The biological importance of NO enforces the need to develop and
      characterize specific and sensitive probes. To date, several fluorophores,
      chromophores and colorimetric techniques have been developed to detect NO or its
      metabolites (NO(2) and NO(3)) in biological fluids, viable cells or cell lysates.
      METHODS: Recently, a novel probe (NO(550)) has been developed and reported to
      detect NO in solutions and in primary astrocytes and neuronal cells with a
      fluorescence signal arising from a nonfluorescent background. RESULTS: Here, we
      report further characterization of this probe by optimizing conditions for the
      detection and imaging of NO products in primary vascular ECs, fibroblasts, and
      embryonic stem cell- and induced pluripotent stem cell-derived ECs in the absence
      and presence of pharmacological agents that modulate NO levels. In addition, we
      studied the stability of this probe in cells over time and evaluated its
      compartmentalization in reference to organelle-labeling dyes. Finally, we
      synthesized an inherently fluorescent diazo ring compound (AZO(550)) that is
      expected to form when the nonfluorescent NO(550) reacts with cellular NO, and
      compared its cellular distribution with that of NO(550). CONCLUSION: NO(550) is a
      promising agent for imaging NO at baseline and in response to pharmacological
      agents that modulate its levels.

PMID- 24335470
TI  - Thoracic and thoracoabdominal aortic repair under regional spinal cord
      hypothermia.
AB  - OBJECTIVES: Spinal cord deficits are devastating complications after surgery for
      thoracic and thoracoabdominal aortic aneurysms. We developed a regional spinal
      cord cooling system using an epidural catheter containing cold saline within an
      isolated counter-current lumen to prevent such complications and reviewed the
      clinical results. METHODS: We enrolled 37 patients with thoracic (n = 13) and
      thoracoabdominal (n = 24) aortic aneurysms that were repaired using the regional
      spinal cord cooling system under mild hypothermia with a partial femoro-femoral
      bypass. RESULTS: Although 2 patients died before hospital discharge (hospital
      mortality, 5.4%), none developed neurological deficits such as paraplegia or
      paraparesis. CONCLUSIONS: The outcomes of surgery for thoracic and
      thoracoabdominal aortic aneurysms under regional spinal cord hypothermia using a
      custom-designed epidural catheter were excellent. Although our patient cohort was
      small, the results indicate that our technique might help to improve the outcomes
      of thoracic and thoracoabdominal aortic repair.

PMID- 24335471
TI  - Distribution of adrenergic and cholinergic nerve fibres within intrinsic nerves
      at the level of the human heart hilum.
AB  - OBJECTIVES: The disbalance between adrenergic (sympathetic) and cholinergic
      (parasympathetic) cardiac inputs facilitates cardiac arrhythmias, including the
      lethal ones. In spite of the fact that the morphological pattern of the
      epicardiac ganglionated subplexuses (ENsubP) has been previously described in
      detail, the distribution of functionally distinct axons in human intrinsic nerves
      was not investigated thus far. Therefore, the aim of the present study was to
      quantitatively evaluate the distribution of tyrosine hydroxylase (TH)- and
      choline acetyltransferase (ChAT)-positive axons within intrinsic nerves at the
      level of the human heart hilum (HH), since they are of pivotal importance for
      determining proper treatment options for different arrhythmias. METHODS: Tissue
      samples containing the intrinsic nerves from seven epicardiac subplexuses were
      obtained from nine human hearts without cardiac pathology and processed for
      immunofluorescent detection of TH and ChAT. The nerve area was measured and the
      numbers of axons were counted using microphotographs of nerve profiles. The
      densities of fibres were extrapolated and compared between subplexuses. RESULTS:
      ChAT-immunoreactive (IR) fibres were evidently predominant (>56%) in nerves of
      dorsal (DRA) and ventral right atrial (VRA) ENsubP. Within both left (LC) and
      right coronary ENsubP, the most abundant (70.9 and 83.0%, respectively) were TH
      IR axons. Despite subplexal dependence, ChAT-IR fibres prevailed in comparatively
      thinner nerves, whereas TH-IR fibres in thicker ones. Morphometry showed that at
      the level of HH: (i) LC subplexal nerves were found to be the thickest (25 737 +/
      4131 MUm(2)) ones, whereas the thinnest (2604 +/- 213 MUm(2)) nerves
      concentrated in DRA ENsubP; (ii) the density of ChAT-IR axons was highest (6.8 +/
      0.6/100 MUm(2)) in the ventral left atrial nerves and lowest (3.2 +/- 0.1/100
      MUm(2)) in left dorsal ENsubP and (iii) the density of TH-IR fibres was highest
      (15.9 +/- 2.1/100 MUm(2)) in LC subplexal nerves and lowest (4.4 +/- 0.3/100
      MUm(2)) in VRA nerves. CONCLUSIONS: (i) The principal intrinsic adrenergic neural
      pathways in the human heart proceed via both coronary ENsubP that supply cardiac
      ventricles and (ii) the majority of cholinergic nerve fibres access the human
      heart through DRA and VRA ENsubP and extend towards the right atrium, including
      the region of the sinuatrial node.

PMID- 24335472
TI  - Intraoperative graft verification in coronary surgery: increased diagnostic
      accuracy adding high-resolution epicardial ultrasonography to transit-time flow
      measurement.
AB  - OBJECTIVES: Transit-time flow measurement (TTFM) allows intraoperative functional
      assessment of grafts in coronary artery bypass grafting (CABG). The major
      limitation of this technique is a low positive predictive value (PPV) that could
      lead to unnecessary graft revisions. A combined approach with high-resolution
      epicardial ultrasonography (HR-ECUS) and TTFM was evaluated for the first time in
      terms of diagnostic accuracy. The aim of this study is to evaluate the added
      value of intraoperative HR-ECUS for an improved graft patency verification.
      METHODS: From November 2009 to September 2012, 333 patients underwent isolated
      CABG. A total number of 717 grafts were performed; all grafts were
      intraoperatively verified by means of both TTFM and HR-ECUS. RESULTS: Among 678
      grafts considered functioning at TTFM, 3 (0.4%) were failing at HR-ECUS and
      promptly redone (2 bilateral internal mammary artery-Y-grafts and 1 left internal
      mammary artery to left anterior descending (LIMA-LAD)). These were confirmed as
      true positive at graft revision due to technical error. HR-ECUS confirmed the
      good functioning of the remaining 675 grafts already demonstrated by TTFM; among
      them, 8 showed high troponin I release (clinical false negative), whereas the
      remaining 667 had no high TnI release (clinical true negative). In 2 of 39 grafts
      malfunctioning at TTFM, HR-ECUS confirmed the graft failure; surgical inspection
      of the anastomosis during redo procedure (in both cases LIMA-to-LAD graft) showed
      a technical error leading to define those 2 grafts as 'true positive' on the
      basis of either direct vision and improved post-redo TTFM parameters. Finally, in
      35 cases, HR-ECUS did not confirm TTFM diagnosis demonstrating a full patency of
      the anastomosis; these grafts had an uneventful clinical course (true negative).
      The main result of this study is the increase of PPV from 10% with TTFM to almost
      100% of TTFM + HR-ECUS, avoiding many unnecessary graft revisions. CONCLUSIONS:
      HR-ECUS should be considered complimentary to TTFM. Simultaneous use of the two
      methods during CABG provides morphological and functional information improving
      considerably diagnostic accuracy of intraoperative graft verification procedure
      close to 100%.

PMID- 24335473
TI  - Dodging two bullets with one dsRNA-binding protein.

PMID- 24335474
TI  - The identification of novel potential injury mechanisms and candidate biomarkers
      in renal allograft rejection by quantitative proteomics.
AB  - Early transplant dysfunction and failure because of immunological and
      nonimmunological factors still presents a significant clinical problem for
      transplant recipients. A critical unmet need is the noninvasive detection and
      prediction of immune injury such that acute injury can be reversed by proactive
      immunosuppression titration. In this study, we used iTRAQ -based proteomic
      discovery and targeted ELISA validation to discover and validate candidate urine
      protein biomarkers from 262 renal allograft recipients with biopsy-confirmed
      allograft injury. Urine samples were randomly split into a training set of 108
      patients and an independent validation set of 154 patients, which comprised the
      clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable
      graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis
      (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control
      (HC) (n = 10). A total of 389 proteins were measured that displayed differential
      abundances across urine specimens of the injury types (p < 0.05) with a
      significant finding that SUMO2 (small ubiquitin-related modifier 2) was
      identified as a "hub" protein for graft injury irrespective of causation. Sixty
      nine urine proteins had differences in abundance (p < 0.01) in AR compared with
      stable graft, of which 12 proteins were up-regulated in AR with a mean fold
      increase of 2.8. Nine urine proteins were highly specific for AR because of their
      significant differences (p < 0.01; fold increase >1.5) from all other transplant
      categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA,
      KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p
      = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were
      validated by ELISA in AR using an independent sample set. The fibrinogen proteins
      further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a
      finding that supports the utility of monitoring these urinary proteins for the
      specific and sensitive noninvasive diagnosis of acute renal allograft rejection. 

PMID- 24335476
TI  - No place to hide: two pilot studies assessing the effectiveness of adding a
      health warning to the cigarette stick.
AB  - OBJECTIVE: To examine whether health warnings printed onto the cigarette stick
      would increase intentions to quit. METHODS: Two experiments with smokers were
      conducted. The first study was conducted in Scotland on 88 adult (aged 18 or
      over) smokers recruited around two university campuses. The second study was
      conducted on 120 adult (aged 16 or over) smokers recruited around inner city
      cafes in Greece. Study 1 tested smokers' ratings of the attractiveness of
      cigarettes printed with either 'minutes of life lost' (minute condition) or
      'toxic constituents' (toxic condition) against a control cigarette as well as the
      change in participants' pre-exposure and postexposure quitting intentions. Study
      2 only assessed the effect of the minute condition on smokers' change in quitting
      intentions. Analysis of variance and paired-samples t tests were undertaken.
      Participants in Study 1 were shown a picture of the stimuli, with participants in
      Study 2 given the actual cigarette to hold. RESULTS: The analyses revealed
      increases in quitting intentions postexposure for the minute condition (mean
      paired difference=0.68, p<0.001) and the toxic condition (mean paired
      difference=0.23, p<0.05) in Study 1. Similar findings were found for the minute
      condition (mean paired difference=0.38, p<0.001) in Study 2. CONCLUSIONS: These
      results suggest that printing a public health warning on the cigarette stick may
      result in higher intentions to quit smoking. However, many other messages (eg,
      benefits of quitting, harmful effects of secondhand smoke) which can be printed
      on the cigarette stick have not been tested in the current studies.

PMID- 24335475
TI  - Matching cross-linked peptide spectra: only as good as the worse identification.
AB  - Chemical cross-linking mass spectrometry identifies interacting surfaces within a
      protein assembly through labeling with bifunctional reagents and identifying the
      covalently modified peptides. These yield distance constraints that provide a
      powerful means to model the three-dimensional structure of the assembly.
      Bioinformatic analysis of cross-linked data resulting from large protein
      assemblies is challenging because each cross-linked product contains two
      covalently linked peptides, each of which must be correctly identified from a
      complex matrix of potential confounders. Protein Prospector addresses these
      issues through a complementary mass modification strategy in which each peptide
      is searched and identified separately. We demonstrate this strategy with an
      analysis of RNA polymerase II. False discovery rates (FDRs) are assessed via
      comparison of cross-linking data to crystal structure, as well as by using a
      decoy database strategy. Parameters that are most useful for positive
      identification of cross-linked spectra are explored. We find that fragmentation
      spectra generally contain more product ions from one of the two peptides
      constituting the cross-link. Hence, metrics reflecting the quality of the
      spectral match to the less confident peptide provide the most discriminatory
      power between correct and incorrect matches. A support vector machine model was
      built to further improve classification of cross-linked peptide hits.
      Furthermore, the frequency with which peptides cross-linked via common acylating
      reagents fragment to produce diagnostic, cross-linker-specific ions is assessed.
      The threshold for successful identification of the cross-linked peptide product
      depends upon the complexity of the sample under investigation. Protein
      Prospector, by focusing the reliability assessment on the least confident
      peptide, is better able to control the FDR for results as larger complexes and
      databases are analyzed. In addition, when FDR thresholds are calculated
      separately for intraprotein and interprotein results, a further improvement in
      the number of unique cross-links confidently identified is achieved. These
      improvements are demonstrated on two previously published cross-linking datasets.

PMID- 24335477
TI  - I 'like' MPOWER: using Facebook, online ads and new media to mobilise tobacco
      control communities in low-income and middle-income countries.
AB  - New media campaigns hold great potential to grow public awareness about the
      dangers of tobacco use and advance tobacco control policies, including in low
      income and middle-income countries (LMICs), which have shared in a decade of
      explosive growth in mobile and internet penetration. With the majority of deaths
      from the tobacco epidemic occurring in LMICs, new media must be harnessed both as
      an advocacy tool to promote social mobilisation around tobacco issues and to
      build public support for MPOWER policies. This paper examines three consecutive
      new media advocacy campaigns that used communication channels such as mobile SMS,
      Facebook and online advertising to promote tobacco control policies. It includes
      some of the lessons learned, such as the pitfalls of relying on viral growth as a
      strategy for obtaining reach and campaign growth; the challenge of translating
      strategies from traditional media to new media; and the importance of
      incorporating marketing strategies such as paid advertising, community organising
      or public relations. It also identifies some of the many knowledge gaps and
      proposes future research directions. 

PMID- 24335478
TI  - Evaluation of a community-based smoking cessation programme for people with
      severe mental illness.
AB  - OBJECTIVE: To evaluate the effectiveness of a smoking cessation programme for
      smokers living with mental illness, provided within community mental health
      services, and determine factors which impact on the rates of cessation. METHODS:
      One hundred and twenty-nine smoking cessation group programmes were provided
      within community mental health services in South Australia between 2006 and 2011.
      Participants' smoking cessation rates were analysed in terms of demographic
      factors, smoking history, diagnosis and group participation. Participants
      completed written questionnaires at registration, at the end of each programme
      and at 12 months. They were also asked to complete the Fagerstrom rating scale
      and use the Micro+Smokerlyzer to measure breath carbon monoxide levels. RESULTS:
      Eight hundred and forty-four smokers living with mental illness registered for
      the programme. Many continued to be involved in addressing their tobacco use over
      more than one programme. At the end of their last programme, 581 completed an
      evaluation and 129 (22.2%) were not smoking. If it is assumed that all who did
      not complete an evaluation had continued smoking, then the cessation rate was
      15.3%. Cessation rates were higher for those who attended more sessions, had
      decided at registration that they wanted to quit or had a lower level of nicotine
      dependence. Cessation rates were not significantly affected by gender, diagnosis
      or the number of years of smoking. CONCLUSIONS: People with mental illness are
      concerned about their tobacco use and will seek help if this is available.
      Smoking cessation programmes which are tailored for this group of smokers can be
      effective and should be provided by mental health and tobacco control services.

PMID- 24335479
TI  - Trends in menthol and non-menthol cigarette consumption in the U.S.A.: 2000-2011.

PMID- 24335480
TI  - DNA methylation profiling can classify HIV-associated lymphomas.
AB  - BACKGROUND: HIV-positive patients have a 60-fold to 200-fold increased incidence
      of non-Hodgkin lymphomas, including Burkitt lymphoma, diffuse large B-cell
      lymphoma, and primary central nervous system lymphoma. HIV-associated lymphomas
      frequently have features such as extranodal involvement, decreased responses to
      standard chemotherapy, and high relapse rates, which indicate a poor prognosis.
      General pathological features do not clearly differentiate HIV-associated
      lymphomas from non-HIV lymphomas. METHODS: To investigate the features of HIV
      associated lymphomas, we performed genome-wide DNA methylation profiling of HIV
      and non-HIV lymphomas using Illumina GoldenGate Methylation Cancer Panel I and
      Illumina Infinium HumanMethylation450 BeadChip microarrays. DNA methylation
      profiles in HIV-associated and non-HIV lymphomas were characterized using
      unsupervised hierarchical clustering analyses. RESULTS: The analyses of promoter
      regions revealed unique DNA methylation profiles in HIV-associated lymphomas,
      suggesting profile differences compared with non-HIV lymphomas, which implies
      specific gene regulation in HIV-associated lymphoma involving DNA methylation.
      Based on HumanMethylation450 BeadChip data, 2541 target sites were selected as
      differing significantly in comparisons between HIV-associated and non-HIV
      associated lymphomas using Wilcoxon's rank-sum test (P <0.05) and Deltabeta
      values more than 0.30. Recurrent cases of HIV-associated lymphoma had different
      profiles compared with nonrecurrent HIV lymphomas. CONCLUSION: DNA methylation
      profiling indicated that 2541 target sites differed significantly in HIV
      associated lymphoma, which may partly explain the poor prognosis. Our data
      indicate that the methylation profiles of target genes have potential in
      elucidating HIV-associated lymphomagenesis and can serve as new prognostic
      markers.

PMID- 24335481
TI  - Anal microbiota profiles in HIV-positive and HIV-negative MSM.
AB  - OBJECTIVE: Because differences in anal microbial populations (microbiota) could
      affect acquisition of HIV or other conditions, especially among MSM, we profiled
      the microbiota of the anal canal, assessed its stability, and investigated
      associations with diversity and composition. DESIGN: Microbiota profiles in anal
      swabs collected from 76 MSM (52 in 1989, swab-1; 66 1-5 years later, swab-2) were
      compared by HIV status (25 HIV-positive), T-cell subsets, and questionnaire data.
      METHODS: Bacterial 16S rRNA genes were amplified, sequenced (Illumina MiSeq), and
      clustered into species-level operational taxonomic units (QIIME and Greengenes).
      Regression models and Wilcoxon tests were used for associations with alpha
      diversity (unique operational taxonomic units, Shannon's index). Composition was
      compared by Adonis (QIIME). RESULTS: Most anal bacteria were Firmicutes (mean
      60.6%, range 21.1-91.1%) or Bacteroidetes (29.4%, 4.1-70.8%). Alpha diversity did
      not change between the two swabs (N = 42 pairs). In swab-2, HIV-positives had
      lower alpha diversity (P <= 0.04) and altered composition, with fewer Firmicutes
      and more Fusobacteria taxa (P <= 0.03), not completely attributable to very low
      CD4(+) cell count (median 232 cells/MUl), prior AIDS clinical diagnosis (N = 17),
      or trimethoprim-sulfamethoxazole use (N = 6). Similar but weaker differences were
      observed in swab-1 (HIV-positive median 580 CD4(+) cells/MUl; no trimethoprim
      sulfamethoxazole). Associations with T-cell subsets, smoking, and sexual
      practices were null or inconsistent. CONCLUSIONS: The anal microbiota of MSM was
      relatively stable over 1-5 years. However, with uncontrolled, advanced HIV
      infection, the microbiota had altered composition and reduced diversity partially
      attributable to antibiotics. Investigations of microbial community associations
      with other immune perturbations and clinical abnormalities are needed.

PMID- 24335482
TI  - Failure to achieve a CD4+ cell count response on combination antiretroviral
      therapy despite consistent viral load suppression.
AB  - OBJECTIVE: To assess CD4 cell count recovery in people severely immunosuppressed
      at start of antiretroviral therapy (ART) who achieve and maintain viral load
      suppression. METHODS: Eligible participants from the UK Collaborative HIV Cohort
      Study started ART with at least three drugs after 1 January 2000. Participants
      were required to have pre-ART CD4 cell count below 100 cells/MUl, at least 2
      years of follow-up on ART, have achieved viral load suppression (<= 50 copies/ml)
      by 9 months after starting ART and to have maintained this throughout follow-up.
      Participants were further required to be regularly engaged with care. We
      calculated the proportion of people who failed to achieve a CD4 cell count of
      more than 100, 150, 200, 350 and 500 cells/MUl by the time of the last follow-up,
      or 5 years from start of ART, whichever occurred first (censoring date). RESULTS:
      Of the 400 participants [median (interquartile range) pre-ART CD4 cell count of
      38 (14-65) cells/MUl], 2 (0.5%), 8 (2%), 28 (7%), 131 (33%) and 259 (65%) failed
      to achieve a CD4 cell count of more than 100, 150, 200, 350 and 500 cells/MUl, by
      the censoring date, respectively. Kaplan-Meier estimates of the proportion of
      people reaching each CD4 cell count threshold after 1 year on ART were 88, 70,
      50, 14 and 3%, respectively, and after 3 years on ART, 98, 95, 90, 59 and 25%,
      respectively. Median (interquartile range) follow-up on ART was 3.9 (2.7-4.8)
      years. CONCLUSION: Given a person with pre-ART CD4 cell count below 100 cells/MUl
      survives and maintains consistent viral load suppression on ART, there is over a
      90% chance of reaching a CD4 cell count above 200 cells/MUl by 3 years.

PMID- 24335483
TI  - Increased glucose metabolic activity is associated with CD4+ T-cell activation
      and depletion during chronic HIV infection.
AB  - OBJECTIVES: Glucose metabolism plays a fundamental role in supporting the growth,
      proliferation and effector functions of T cells. We investigated the impact of
      HIV infection on key processes that regulate glucose uptake and metabolism in
      primary CD4 and CD8 T cells. DESIGN AND METHODS: Thirty-eight HIV-infected
      treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term
      nonprogressors and 25 HIV control individuals were studied. Basal markers of
      glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake,
      intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The
      cellular markers of immune activation, CD38 and HLA-DR, were measured by flow
      cytometry. RESULTS: The surface expression of the Glut1 is up-regulated in CD4 T
      cells in HIV-infected patients compared with uninfected controls. The percentage
      of circulating CD4Glut1 T cells was significantly increased in HIV-infected
      patients and was not restored to normal levels following combination
      antiretroviral therapy. Basal markers of glycolysis were significantly higher in
      CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 T cells
      correlated positively with the expression of the cellular activation marker, HLA
      DR, on total CD4 T cells, but inversely with the absolute CD4 T-cell count
      irrespective of HIV treatment status. CONCLUSION: Our data suggest that Glut1 is
      a potentially novel and functional marker of CD4 T-cell activation during HIV
      infection. In addition, Glut1 expression on CD4 T cells may be exploited as a
      prognostic marker for CD4 T-cell loss during HIV disease progression.

PMID- 24335484
TI  - The risk factors of severe acute kidney injury induced by cisplatin.
AB  - OBJECTIVES: We reported that the KDIGO (Kidney Disease: Improving Global
      Outcomes) criteria could stratify the risk of mortality in acute kidney injury
      (AKI) caused by cisplatin. The purpose of this study was to investigate risk
      factors of severe cisplatin-induced AKI (CIA). METHODS: From January 2006 to
      December 2012, we identified Japanese cancer patients who were treated with
      cisplatin as a first-line chemotherapy at Nagoya University Hospital. Serum
      creatinine levels were used to define CIA. RESULTS: We evaluated 1,721 patients
      treated with cisplatin. In multivariable analysis, cisplatin dosages/m(2) [odds
      ratio (OR) 1.019] or diagnosis of cancer stage 4 (OR 1.797) were risk factors of
      moderate CIA. History of diabetes mellitus (OR 3.454), history of cardiovascular
      disease (OR 3.612) or diagnosis of cancer stage 4 (OR 2.610) were risk factors of
      severe CIA. CONCLUSIONS: Diabetes mellitus, cardiovascular disease and advanced
      cancer increased the risk of severe CIA. As severe CIA shortens the survival
      period, we should consider whether the use of cisplatin benefits these patients.

PMID- 24335486
TI  - Markers associated with persisting low-level viraemia under antiretroviral
      therapy in HIV-1 infection.
AB  - OBJECTIVES: To identify host and viral characteristics associated with long-term
      persisting low-level viraemia (PLLV) under antiretroviral therapy (ART). PATIENTS
      AND METHODS: Seventy-one ART-treated patients with long-term PLLV (20-250
      copies/mL) and 102 control patients with systematically undetectable viral load
      (VL) were selected retrospectively from ART-treated patients followed at the
      Ghent HIV reference centre. Host and viral characteristics were compared using
      univariate and multivariate analyses. RESULTS: Higher plasma VL at therapy
      initiation (OR 3.52; 95% CI 1.86-6.65; P < 0.001), therapy re-initiation after an
      interruption (OR 3.94; 95% CI 1.70-9.16; P = 0.001), male gender (OR 4.28; 95% CI
      1.40-13.00; P = 0.011), a protease inhibitor-based regimen (OR 2.90; 95% CI 1.20
      6.97; P = 0.017) and predicted CCR5 co-receptor tropism (OR 2.53; 95% CI 1.05
      6.11; P = 0.039) were independently associated with PLLV. CONCLUSIONS: VL at ART
      initiation, therapy history, gender, ART regimen and co-receptor tropism were
      independently associated with PLLV. Gender, therapy history, co-receptor tropism
      and VL at ART initiation could be valuable predictive markers to identify
      patients at risk for PLLV.

PMID- 24335485
TI  - Rapid kill of malaria parasites by artemisinin and semi-synthetic endoperoxides
      involves ROS-dependent depolarization of the membrane potential.
AB  - OBJECTIVES: Artemisinin and artemisinin semi-synthetic derivatives (collectively
      known as endoperoxides) are first-line antimalarials for the treatment of
      uncomplicated and severe malaria. Endoperoxides display very fast killing rates
      and are generally recalcitrant to parasite resistance development. These key
      pharmacodynamic features are a result of a complex mechanism of action, the
      details of which lack consensus. Here, we report on the primary physiological
      events leading to parasite death. METHODS: Parasite mitochondrial (DeltaPsim) and
      plasma membrane (DeltaPsip) electrochemical potentials were measured using real
      time single-cell imaging following exposure to pharmacologically relevant
      concentrations of endoperoxides (artemisinin, dihydroartemisinin, artesunate and
      the synthetic tetraoxane RKA182). In addition, mitochondrial electron transport
      chain components NADH:quinone oxidoreductase (alternative complex I), bc1
      (complex III) and cytochrome oxidase (complex IV) were investigated to determine
      their functional sensitivity to the various endoperoxides. RESULTS: Parasite
      exposure to endoperoxides resulted in rapid depolarization of parasite DeltaPsim
      and DeltaPsip. The rate of depolarization was decreased in the presence of a
      reactive oxygen species (ROS) scavenger and Fe(3+) chelators. Depolarization of
      DeltaPsim by endoperoxides is not believed to be through the inhibition of
      mitochondrial electron transport chain components, owing to the lack of
      significant inhibition when assayed directly. CONCLUSIONS: The depolarization of
      DeltaPsim and DeltaPsip is shown to be mediated via the generation of ROS that
      are initiated by iron bioactivation of endoperoxides and/or catalysed by iron
      dependent oxidative stress. These data are discussed in the context of current
      hypotheses concerning the mode of action of endoperoxides.

PMID- 24335488
TI  - Sensitization of erythrocytes to suicidal erythrocyte death following water
      deprivation.
AB  - BACKGROUND/AIMS: Klotho deficiency results in excessive formation of 1,25(OH)2D3,
      accelerated ageing and early death. Moreover, klotho deficiency enhances
      eryptosis, the suicidal erythrocyte death characterized by phosphatidylserine
      exposure at the erythrocyte surface. Triggers of eryptosis include increase of
      cytosolic Ca(2+)-activity ([Ca(2+)]i), glucose depletion, hyperosmotic shock and
      oxidative stress. Klotho expression is decreased and 1,25(OH)2D3-formation
      enhanced by dehydration. The present study thus explored whether dehydration
      influences eryptosis. METHODS: Blood was drawn from hydrated or 36h dehydrated
      mice. Plasma osmolarity was determined by vapour pressure method, plasma
      1,25(OH)2D3 and aldosterone concentrations using ELISA, and plasma Ca(2+)
      concentration utilizing photometry. Erythrocytes were exposed to Ca(2+)-ionophore
      ionomycin (1 uM, 30 min), energy depletion (12 h glucose removal), hyperosmotic
      shock (500 mM sucrose added, 2 h) and oxidative stress (100 uM tert-butyl
      hydroperoxide, 30 min) and phosphatidylserine exposure at the erythrocyte surface
      estimated from annexin V binding. RESULTS: Dehydration increased plasma
      osmolarity and plasma 1,25(OH)2D3 and aldosterone concentrations. Dehydration did
      not significantly modify phosphatidylserine-exposure of freshly drawn
      erythrocytes but significantly enhanced the increase of phosphatidylserine
      exposure under control conditions and following treatment with ionomycin, glucose
      deprivation, hyperosmolarity or tert-butyl-hydroperoxide. CONCLUSIONS:
      Dehydration sensitizes the erythrocytes to spontaneous eryptosis and to the
      triggering of eryptosis by excessive Ca(2+)-entry, energy depletion, hyperosmotic
      shock and oxidative stress.

PMID- 24335487
TI  - Severe sepsis and septic shock: management and performance improvement.
AB  - Morbidity and mortality from sepsis remains unacceptably high. Large variability
      in clinical practice, plus the increasing awareness that certain processes of
      care associated with improved critical care outcomes, has led to the development
      of clinical practice guidelines in a variety of areas related to infection and
      sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and
      Septic Shock were first published in 2004, revised in 2008, and recently revised
      again and published in 2013. The first part of this manuscript is a summary of
      the 2013 guidelines with some editorial comment. The second part of the
      manuscript characterizes hospital based sepsis performance improvement programs
      and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key
      component of such a program. 

PMID- 24335489
TI  - Mitochondrial metabolism in TCA cycle mutant cancer cells.

PMID- 24335490
TI  - Online social support received by patients with cancer.
AB  - Patient education in the public healthcare system does not necessarily meet the
      needs of patients with cancer. Because of this, they may turn to the Internet, or
      they are guided to electronic sources of social support. The purposes of this
      study were to describe what kind of social support patients with cancer receive
      from the Internet and its meaning for them. The data were collected using an
      online survey that consisted of open-ended questions based on a theory of online
      social support. The data were analyzed using an inductive content analysis.
      Online social support consisted of three categories: disease-related information
      from reliable sources, supportive interaction enhancing positive emotions, and
      practical tips for daily life with cancer. Three major categories related to the
      meaning of online social support were identified: peers helping make life easier,
      empowerment, and inadequate support. The findings can be utilized in tailoring
      educational interventions for patients with cancer. In the future, the long
      lasting effects of online social support need to be examined. 

PMID- 24335491
TI  - Effects of high-fidelity patient simulation on nursing students' resuscitation
      specific self-efficacy.
AB  - The purpose of this study was to assess the difference in measures of pretest and
      posttest self-efficacy following simulation-based training and to compare
      differences in self-efficacy between nursing students exposed to medium- or high
      fidelity patient simulations. This study used a nonequivalent control group
      pretest-posttest design. A convenience sample of 163 second-year nursing students
      was assigned to either the high-fidelity patient simulation group (n = 28) or
      medium-fidelity simulation group (n = 135). Resuscitation-specific self-efficacy
      was measured at pretest and posttest. The overall mean self-efficacy score was
      higher at posttest compared with pretest in both the high-fidelity group (t =
      9.327, P < .001) and medium-fidelity group (t = 6.568, P < .001). Nursing
      students exposed to high-fidelity patient simulation reported significantly
      higher scores on a debriefing and recording subscale (t = 5.578, P < .001),
      responding and rescuing subscale (t = 5.811, P < .001), reporting subscale (t =
      3.441, P = .001), and overall scale score (t = 4.737, P < .001) compared with the
      medium-fidelity simulation group. Simulation-based training has a positive impact
      on improving self-efficacy. Additional high-fidelity simulation is more effective
      than medium-fidelity simulation only in improving nursing students' self
      efficacy. There is a need to boost the self-efficacy of the students through
      mastery experiences in their learning curriculum. 

PMID- 24335492
TI  - Light for nurses' work in the 21st century: a review of lighting, human vision
      limitations, and medication administration.
AB  - A literature review was conducted to determine the state of the science related
      to medication errors and light. The limited literature is discussed in
      relationship to human vision and light needs. Little systematic action has been
      taken to increase nurses' awareness of the connection between lighting and
      potential medication errors. Implications for nursing practice and research about
      light conditions are provided. Interventions from other industries may aid
      nursing in making decisions about light conditions. 

PMID- 24335493
TI  - On the biogeography of Centipeda: a species-tree diffusion approach.
AB  - Reconstructing the biogeographic history of groups present in continuous arid
      landscapes is challenging due to the difficulties in defining discrete areas for
      analyses, and even more so when species largely overlap both in terms of
      geography and habitat preference. In this study, we use a novel approach to
      estimate ancestral areas for the small plant genus Centipeda. We apply continuous
      diffusion of geography by a relaxed random walk where each species is sampled
      from its extant distribution on an empirical distribution of time-calibrated
      species-trees. Using a distribution of previously published substitution rates of
      the internal transcribed spacer (ITS) for Asteraceae, we show how the evolution
      of Centipeda correlates with the temporal increase of aridity in the arid zone
      since the Pliocene. Geographic estimates of ancestral species show a consistent
      pattern of speciation of early lineages in the Lake Eyre region, with a division
      in more northerly and southerly groups since ~840 ka. Summarizing the geographic
      slices of species-trees at the time of the latest speciation event (~20 ka),
      indicates no presence of the genus in Australia west of the combined desert belt
      of the Nullabor Plain, the Great Victoria Desert, the Gibson Desert, and the
      Great Sandy Desert, or beyond the main continental shelf of Australia. The result
      indicates all western occurrences of the genus to be a result of recent dispersal
      rather than ancient vicariance. This study contributes to our understanding of
      the spatiotemporal processes shaping the flora of the arid zone, and offers a
      significant improvement in inference of ancestral areas for any organismal group
      distributed where it remains difficult to describe geography in terms of discrete
      areas. 

PMID- 24335494
TI  - The PCL index is correlated with the control of rotational kinematics that is
      achieved after anatomic anterior cruciate ligament reconstruction.
AB  - BACKGROUND: The posterior cruciate ligament (PCL) index quantifies the curvature
      of the PCL seen on magnetic resonance imaging (MRI) that is caused by a change in
      tibiofemoral alignment in the anterior cruciate ligament (ACL)-deficient knee. It
      has been proposed that the PCL index may be useful in assessing the success of
      ACL reconstruction (ACLR). Hypothesis/ PURPOSE: The purpose of this study was to
      test if the PCL index is predictive of in vivo rotational kinematics and joint
      laxity measures in knees of patients after single-bundle ACLR. The hypothesis was
      that the PCL index is predictive of rotational knee kinematics and objective
      laxity scores. STUDY DESIGN: Controlled laboratory study. METHODS: At a mean of
      18.1 months postoperatively, the PCL index was defined on MRI in 16 patients
      prospectively followed up after anatomic single-bundle ACLR and in 16 matched
      controls. The patients were evaluated with 3-dimensional motion analysis during
      (1) descending and pivoting as well as (2) landing and pivoting tasks. The side
      to-side difference in tibial rotation range of motion between the reconstructed
      knee and the contralateral intact knee was calculated. The side-to-side
      difference in anterior tibial translation was measured with a KT-1000
      arthrometer. Linear regression models were used with the PCL index as a predictor
      of the side-to-side difference in tibial rotation for each task and the side-to
      side difference in anterior tibial translation. RESULTS: The PCL index of the
      reconstructed knees was significantly lower compared with that of the control
      knees (P < .001). The index was predictive of the side-to-side difference in
      tibial rotation during both tasks (R (2) = 0.472 and 0.477, P = .003), with a
      lower index being indicative of increased rotational laxity. It was not
      predictive of anterior tibial translation (at 134 N: R (2) = 0.13, P = .17; at
      maximum force: R (2) = 0.009, P = .726). CONCLUSION: The PCL index after anatomic
      single-bundle ACLR using a bone-patellar tendon-bone graft is predictive of
      rotational kinematics during in vivo dynamic pivoting activities. The results
      show that the PCL index is correlated with the postoperative ability to control
      rotational kinematics of the knee joint. CLINICAL RELEVANCE: This study provides
      evidence regarding the interplay between restoration of the native ACL's anatomy
      and the PCL's appearance and suggests that the effective restoration of
      tibiofemoral alignment after ACLR that is reflected in the PCL index translates
      into better functional outcomes as measured by tibial rotation during pivoting
      activities.

PMID- 24335495
TI  - The diagnostic and prognostic value of ultrasonography in soccer players with
      acute hamstring injuries.
AB  - BACKGROUND: An injury to the hamstring muscle complex is the most common injury
      in soccer. Ultrasound of acute hamstring injuries is often used as a clinical
      tool for diagnosing hamstring injuries and guiding players in when they can
      return to play. PURPOSE: To (1) investigate the characteristic sonographic
      findings of acute hamstring injuries in soccer players, (2) compare the mean
      injury severity (time to return to play) in injured players with and without
      sonographically verified abnormalities, and (3) correlate the length of the
      injured area and absence from soccer play (time to return to play) to investigate
      if ultrasonography can be used as a prognostic indicator of time to return to
      play. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Players from 50
      teams participating in 1 of the top 5 Danish soccer divisions were followed in
      the period from January to December 2008. Of 67 players with acute hamstring
      injuries, 51 underwent ultrasonographic examination of the injured thigh and were
      included in this study. RESULTS: Ultrasonographic examinations were performed 1
      to 10 days after injury (mean, 5.2 +/- 3.0 days), and sonographic findings were
      present in 31 of 51 cases (61%). Two thirds of the injuries were to the biceps
      femoris muscle and one third to the semitendinosus muscle. No total ruptures were
      documented. The 51 acute hamstring injuries resulted in absence from soccer of a
      mean 25.4 +/- 15.7 days per injury, with no significant difference between
      players with and without sonographically verified abnormalities (P = .41). No
      correlation existed between the length of the injured area and injury severity (r
      = 0.19, P = .29). CONCLUSION: The biceps femoris is the most commonly injured
      hamstring muscle detected by ultrasound, and more than half of the injuries are
      intramuscular. Because neither the presence of sonographic findings nor the size
      of the findings was correlated with time to return to play in injured soccer
      players, the prognosis of hamstring injuries should not be guided by these
      findings alone.

PMID- 24335496
TI  - Molecular evidence for the localization of Plasmodium falciparum immature
      gametocytes in bone marrow.
AB  - Plasmodium falciparum immature gametocytes are not observed in peripheral blood.
      However, gametocyte stages in organs such as bone marrow have never been assessed
      by molecular techniques, which are more sensitive than optical microscopy. We
      quantified P falciparum sexual stages in bone marrow (n = 174) and peripheral
      blood (n = 70) of Mozambican anemic children by quantitative polymerase chain
      reaction targeting transcripts specific for early (PF14_0748; PHISTa),
      intermediate (PF13_0247; Pfs48/45), and mature (PF10_0303; Pfs25) gametocytes.
      Among children positive for the P falciparum housekeeping gene (PF08_0085;
      ubiquitin-conjugating enzyme gene) in bone marrow (n = 136) and peripheral blood
      (n = 25), prevalence of immature gametocytes was higher in bone marrow than
      peripheral blood (early: 95% vs 20%, P < .001; intermediate: 80% vs 16%; P <
      .001), as were transcript levels (P < .001 for both stages). In contrast, mature
      gametocytes were more prevalent (100% vs 51%, P < .001) and abundant (P < .001)
      in peripheral blood than in the bone marrow. Severe anemia (3.57, 95% confidence
      interval 1.49-8.53) and dyserythropoiesis (6.21, 95% confidence interval 2.24
      17.25) were independently associated with a higher prevalence of mature
      gametocytes in bone marrow. Our results highlight the high prevalence and
      abundance of early sexual stages in bone marrow, as well as the relationship
      between hematological disturbances and gametocyte development in this tissue. 

PMID- 24335497
TI  - High-level transgene expression in induced pluripotent stem cell-derived
      megakaryocytes: correction of Glanzmann thrombasthenia.
AB  - Megakaryocyte-specific transgene expression in patient-derived induced
      pluripotent stem cells (iPSCs) offers a new approach to study and potentially
      treat disorders affecting megakaryocytes and platelets. By using a Gp1ba
      promoter, we developed a strategy for achieving a high level of protein
      expression in human megakaryocytes. The feasibility of this approach was
      demonstrated in iPSCs derived from two patients with Glanzmann thrombasthenia
      (GT), an inherited platelet disorder caused by mutations in integrin
      alphaIIbbeta3. Hemizygous insertion of Gp1ba promoter-driven human alphaIIb
      complementary DNA into the AAVS1 locus of iPSCs led to high alphaIIb messenger
      RNA and protein expression and correction of surface alphaIIbbeta3 in
      megakaryocytes. Agonist stimulation of these cells displayed recovery of integrin
      alphaIIbbeta3 activation. Our findings demonstrate a novel approach to studying
      human megakaryocyte biology as well as functional correction of the GT defect,
      offering a potential therapeutic strategy for patients with diseases that affect
      platelet function. 

PMID- 24335498
TI  - Mutations in the cohesin complex in acute myeloid leukemia: clinical and
      prognostic implications.
AB  - Mutations in the cohesin complex are novel, genetic lesions in acute myeloid
      leukemia (AML) that are not well characterized. In this study, we analyzed the
      frequency, clinical, and prognostic implications of mutations in STAG1, STAG2,
      SMC1A, SMC3, and RAD21, all members of the cohesin complex, in a cohort of 389
      uniformly treated AML patients by next generation sequencing. We identified a
      total of 23 patients (5.9%) with somatic mutations in 1 of the cohesin genes. All
      gene mutations were mutually exclusive, and STAG1 (1.8%), STAG2 (1.3%), and SMC3
      (1.3%) were most frequently mutated. Patients with any cohesin complex mutation
      had lower BAALC expression levels. We found a strong association between
      mutations affecting the cohesin complex and NPM1. Mutated allele frequencies were
      similar between NPM1 and cohesin gene mutations. Overall survival (OS), relapse
      free survival (RFS), and complete remission rates (CR) were not influenced by the
      presence of cohesin mutations (OS: hazard ratio [HR] 0.98; 95% confidence
      interval [CI], 0.56-1.72 [P = .94]; RFS: HR 0.7; 95% CI, 0.36-1.38 [P = .3]; CR:
      mutated 83% vs wild-type 76% [P = .45]). The cohesin complex presents a novel
      pathway affected by recurrent mutations in AML. This study is registered at
      www.clinicaltrials.gov as #NCT00209833. 

PMID- 24335499
TI  - Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I
      BET762.
AB  - The bromodomain and extraterminal (BET) protein BRD2-4 inhibitors hold
      therapeutic promise in preclinical models of hematologic malignancies. However,
      translation of these data to molecules suitable for clinical development has yet
      to be accomplished. Herein we expand the mechanistic understanding of BET
      inhibitors in multiple myeloma by using the chemical probe molecule I-BET151. I
      BET151 induces apoptosis and exerts strong antiproliferative effect in vitro and
      in vivo. This is associated with contrasting effects on oncogenic MYC and HEXIM1,
      an inhibitor of the transcriptional activator P-TEFb. I-BET151 causes
      transcriptional repression of MYC and MYC-dependent programs by abrogating
      recruitment to the chromatin of the P-TEFb component CDK9 in a BRD2-4-dependent
      manner. In contrast, transcriptional upregulation of HEXIM1 is BRD2-4
      independent. Finally, preclinical studies show that I-BET762 has a favorable
      pharmacologic profile as an oral agent and that it inhibits myeloma cell
      proliferation, resulting in survival advantage in a systemic myeloma xenograft
      model. These data provide a strong rationale for extending the clinical testing
      of the novel antimyeloma agent I-BET762 and reveal insights into biologic
      pathways required for myeloma cell proliferation. 

PMID- 24335500
TI  - Clot contraction: compression of erythrocytes into tightly packed polyhedra and
      redistribution of platelets and fibrin.
AB  - Contraction of blood clots is necessary for hemostasis and wound healing and to
      restore flow past obstructive thrombi, but little is known about the structure of
      contracted clots or the role of erythrocytes in contraction. We found that
      contracted blood clots develop a remarkable structure, with a meshwork of fibrin
      and platelet aggregates on the exterior of the clot and a close-packed,
      tessellated array of compressed polyhedral erythrocytes within. The same results
      were obtained after initiation of clotting with various activators and also with
      clots from reconstituted human blood and mouse blood. Such close-packed arrays of
      polyhedral erythrocytes, or polyhedrocytes, were also observed in human arterial
      thrombi taken from patients. The mechanical nature of this shape change was
      confirmed by polyhedrocyte formation from the forces of centrifugation of blood
      without clotting. Platelets (with their cytoskeletal motility proteins) and
      fibrin(ogen) (as the substrate bridging platelets for contraction) are required
      to generate the forces necessary to segregate platelets/fibrin from erythrocytes
      and to compress erythrocytes into a tightly packed array. These results
      demonstrate how contracted clots form an impermeable barrier important for
      hemostasis and wound healing and help explain how fibrinolysis is greatly
      retarded as clots contract. 

PMID- 24335502
TI  - Earlier onset and poor prognosis of lung cancer in imprisoned patients.
AB  - INTRODUCTION: Prison inmates are known to be more exposed to various lung cancer
      risk factors, and some studies have shown that lung cancer is the most common
      cancer in prisoners. However, no study has particularly focused on lung cancer
      features in this population. METHOD: Charts of patients with lung cancer
      hospitalized in one of the French secured hospital units between 1997 and 2012
      were reviewed. Data from this cohort were then compared to those of two large
      observational studies conducted in 2000 and 2010 (KBP studies). RESULTS: Thirty
      two cases were included. All were men. The mean age was 52.2 +/- 11.5 years,
      which was significantly lower than in the KBP-2000 (64.4 years) and KBP-2010
      (65.5 years; both p < 0.0001) studies. The percentage of current smokers was much
      higher in prisoners (87.1 vs. 52.2 and 49.2%, respectively; both p < 0.001).
      Ninety percent of prisoners presented with at least one comorbidity. Lung cancer
      clinical presentation did not differ between prisoners and the reference
      populations. The median overall survival was 5.8 months (range 0-15.1) for all
      stages and 4.7 months (range 2.8-6.6) for stage IIIB/IV. CONCLUSION: Although our
      study suffers from limitations, prisoners seem to develop lung cancer at a
      younger age and their prognosis is poor.

PMID- 24335501
TI  - Polyphosphate suppresses complement via the terminal pathway.
AB  - Polyphosphate, synthesized by all cells, is a linear polymer of inorganic
      phosphate. When released into the circulation, it exerts prothrombotic and
      proinflammatory activities by modulating steps in the coagulation cascade. We
      examined the role of polyphosphate in regulating the evolutionarily related
      proteolytic cascade complement. In erythrocyte lysis assays, polyphosphate
      comprising more than 1000 phosphate units suppressed total hemolytic activity
      with a concentration to reduce maximal lysis to 50% that was 10-fold lower than
      with monophosphate. In the ion- and enzyme-independent terminal pathway
      complement assay, polyphosphate suppressed complement in a concentration- and
      size-dependent manner. Phosphatase-treated polyphosphate lost its ability to
      suppress complement, confirming that polymer integrity is required. Sequential
      addition of polyphosphate to the terminal pathway assay showed that polyphosphate
      interferes with complement only when added before formation of the C5b-7 complex.
      Physicochemical analyses using native gels, gel filtration, and differential
      scanning fluorimetry revealed that polyphosphate binds to and destabilizes C5b,6,
      thereby reducing the capacity of the membrane attack complex to bind to and lyse
      the target cell. In summary, we have added another function to polyphosphate in
      blood, demonstrating that it dampens the innate immune response by suppressing
      complement. These findings further establish the complex relationship between
      coagulation and innate immunity. 

PMID- 24335503
TI  - Applicability of chronic kidney disease epidemiology collaboration equations in a
      Chinese population.
AB  - BACKGROUND: Accurate estimated glomerular filtration rates (eGFR) is an important
      step in the diagnosis of chronic kidney disease (CKD). The Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) equation, based on creatinine alone
      (eGFRcr), was developed to improve on the Modification of Diet in Renal Disease
      equation, in particular by addressing the systematic underestimation of high GFR.
      Whether the CKD-EPI equation, based on cystatin C alone (eGFRcys), or the
      combined creatinine-cystatin C CKD-EPI equation (eGFRcr-cys C), actually perform
      better than the CKD-EPI equation based on creatinine (eGFRcr) remains unknown,
      especially in Asians including Chinese populations, where eGFR equations may
      overestimate true GFR. METHODS: A standard dual plasma sampling method (DPSM) of
      estimating (99m)Tc-diethylene triamine penta-acetic acid clearance was used to
      determine the reference or measured GFR (mGFR). Linear regression analysis, Bland
      Altman analysis, bias, absolute bias and accuracy (P30) were used to compare the
      performance of the combined creatinine-cystatin C equation (eGFRcr-cys) and
      equations based on each marker alone (eGFRcr and eGFRcys) in Chinese subjects,
      including both patients with CKD and healthy individuals. RESULTS: We enrolled
      617 Chinese participants (49.11% female, 47.11 +/- 17.25 years old), with a mean
      mGFR of 73.80 +/- 37.55 mL/min/1.73 m(2). The predictive abilities (r), the
      accuracy (P15, P30, P50), bias and absolute bias of the eGFRcr-cys equation were
      superior to eGFRcr equation and the eGFRcys equation in overall samples. Bland
      Altman analysis also demonstrated a consistent result. When compared in
      subgroups, the accuracy (P30) of all three equations exceeded 90% at mGFR >=90
      mL/min/1.73m(2); the eGFRcr-cys equation had the highest accuracy (P30: 95.56%).
      At mGFR 60-89 mL/min/1.73 m(2), the accuracies (P30) of the eGFRcr-cys and eGFRcr
      equations exceeded the acceptable level (>=70%), and there was no significant
      difference between them (P = 0.58). At mGFR <60 mL/min/1.73 m(2), the accuracy
      (P30) of all three equations was below 70%, but the eGFRcr-cys equation had the
      greatest precision. CONCLUSIONS: The performances of the eGFRcr-cys and eGFRcr
      equations were similar to superior to that of the eGFRcys equation at higher GFR
      levels in an Asian population, especially in normal and mild to moderate kidney
      disease. Further improvement is needed for these equations at GFR <60 mL/min per
      1.73 m(2).

PMID- 24335504
TI  - Vascular endothelium: a vulnerable transit zone for merciless sodium.
AB  - In humans, when plasma sodium concentration rises slightly beyond 140 mM,
      vascular endothelium sharply stiffens and nitric oxide release declines. In
      search of a vascular sodium sensor, the endothelial glycocalyx was identified as
      being a negatively charged biopolymer capable of selectively buffering sodium
      ions. Sodium excess damages the glycocalyx and renders vascular endothelium
      increasingly permeable for sodium. In the long term, sodium accumulates in the
      interstitium and gradually damages the organism. It was discovered that
      circulating red blood cells (RBC) 'report' surface properties of the vascular
      endothelium. To some extent, the RBC glycocalyx mirrors the endothelial
      glycocalyx. A poor (charge-deprived) endothelial glycocalyx causes a poor RBC
      glycocalyx and vice versa. This observation led to the assumption that the
      current state of an individual's vascular endothelium in terms of electrical
      surface charges and sodium-buffering capabilities could be read simply from a
      blood sample. Recently, a so-called salt blood test was introduced that
      quantifies the RBC sodium buffer capacity and thus characterizes the endothelial
      function. The arguments are outlined in this article spanning a bridge from
      cellular nano-mechanics to clinical application. 

PMID- 24335505
TI  - Cold-induced cysts of the photosynthetic dinoflagellate Lingulodinium polyedrum
      have an arrested circadian bioluminescence rhythm and lower levels of protein
      phosphorylation.
AB  - Dinoflagellates are microscopic, eukaryotic, and primarily marine plankton.
      Temporary cyst formation is a well-known physiological response of dinoflagellate
      cells to environmental stresses. However, the molecular underpinnings of cold
      induced cyst physiology have never been described. Cultures of the photosynthetic
      dinoflagellate Lingulodinium polyedrum readily form temporary cysts when placed
      at low (8 degrees C+/-1 degrees C) temperature and excyst to form normal motile
      cells following a return to normal temperature (18 degrees C+/-1 degrees C). The
      normal circadian bioluminescence rhythm and the expected changes in Luciferin
      Binding Protein abundance were arrested in L. polyedrum cysts. Furthermore, after
      excystment, the bioluminescence rhythm initiates at a time corresponding to
      zeitgeber 12, independent of the time when the cells encysted. Phosphoprotein
      staining after two-dimensional polyacrylamide gel electrophoresis, as well as
      column-based phosphoprotein enrichment followed by liquid chromatography tandem
      mass spectrometry, showed cyst proteins are hypophosphorylated when compared with
      those from motile cells, with the most marked decreases found for predicted
      Casein Kinase2 target sites. In contrast to the phosphoproteome, the cyst
      proteome is not markedly different from motile cells, as assessed by two
      dimensional polyacrylamide gel electrophoresis. In addition to changes in the
      phosphoproteome, RNA sequencing revealed that cysts show a significant decrease
      in the levels of 132 RNAs. Of the 42 RNAs that were identified by sequence
      analysis, 21 correspond to plastid-encoded gene products and 11 to nuclear
      encoded cell wall/plasma membrane components. Our data are consistent with a
      model in which the highly reduced metabolism in cysts is achieved primarily by
      alterations in the phosphoproteome. The stalling of the circadian rhythm suggests
      temporary cysts may provide an interesting model to address the circadian system
      of dinoflagellates.

PMID- 24335506
TI  - A conserved KIN17 curved DNA-binding domain protein assembles with SQUAMOSA
      PROMOTER-BINDING PROTEIN-LIKE7 to adapt Arabidopsis growth and development to
      limiting copper availability.
AB  - Proper copper (Cu) homeostasis is required by living organisms to maintain
      essential cellular functions. In the model plant Arabidopsis (Arabidopsis
      thaliana), the SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE7 (SPL7) transcription
      factor participates in reprogramming global gene expression during Cu
      insufficiency in order to improve the metal uptake and prioritize its
      distribution to Cu proteins of major importance. As a consequence, spl7 null
      mutants show morphological and physiological disorders during Cu-limited growth,
      resulting in lower fresh weight, reduced root elongation, and chlorosis. On the
      other hand, the Arabidopsis KIN17 homolog belongs to a well-conserved family of
      essential eukaryotic nuclear proteins known to be stress activated and involved
      in DNA and possibly RNA metabolism in mammals. In the study presented here, we
      uncovered that Arabidopsis KIN17 participates in promoting the Cu deficiency
      response by means of a direct interaction with SPL7. Moreover, the double mutant
      kin17-1 spl7-2 displays an enhanced Cu-dependent phenotype involving growth
      arrest, oxidative stress, floral bud abortion, and pollen inviability. Taken
      together, the data presented here provide evidence for SPL7 and KIN17 protein
      interaction as a point of convergence in response to both Cu deficiency and
      oxidative stress. 

PMID- 24335507
TI  - Specificity of the cyanobacterial orange carotenoid protein: influences of orange
      carotenoid protein and phycobilisome structures.
AB  - Cyanobacteria have developed a photoprotective mechanism that decreases the
      energy arriving at the reaction centers by increasing thermal energy dissipation
      at the level of the phycobilisome (PB), the extramembranous light-harvesting
      antenna. This mechanism is triggered by the photoactive Orange Carotenoid Protein
      (OCP), which acts both as the photosensor and the energy quencher. The OCP binds
      the core of the PB. The structure of this core differs in diverse cyanobacterial
      strains. Here, using two isolated OCPs and four classes of PBs, we demonstrated
      that differences exist between OCPs related to PB binding, photoactivity, and
      carotenoid binding. Synechocystis PCC 6803 (hereafter Synechocystis) OCP, but not
      Arthrospira platensis PCC 7345 (hereafter Arthrospira) OCP, can attach echinenone
      in addition to hydroxyechinenone. Arthrospira OCP binds more strongly than
      Synechocystis OCP to all types of PBs. Synechocystis OCP can strongly bind only
      its own PB in 0.8 m potassium phosphate. However, if the Synechocystis OCP binds
      to the PB at very high phosphate concentrations (approximately 1.4 m), it is able
      to quench the fluorescence of any type of PB, even those isolated from strains
      that lack the OCP-mediated photoprotective mechanism. Thus, the determining step
      for the induction of photoprotection is the binding of the OCP to PBs. Our
      results also indicated that the structure of PBs, at least in vitro,
      significantly influences OCP binding and the stabilization of OCP-PB complexes.
      Finally, the fact that the OCP induced large fluorescence quenching even in the
      two-cylinder core of Synechococcus elongatus PBs strongly suggested that OCP
      binds to one of the basal allophycocyanin cylinders. 

PMID- 24335508
TI  - Multiple rice microRNAs are involved in immunity against the blast fungus
      Magnaporthe oryzae.
AB  - MicroRNAs (miRNAs) are indispensable regulators for development and defense in
      eukaryotes. However, the miRNA species have not been explored for rice (Oryza
      sativa) immunity against the blast fungus Magnaporthe oryzae, the most
      devastating fungal pathogen in rice production worldwide. Here, by deep
      sequencing small RNA libraries from susceptible and resistant lines in normal
      conditions and upon M. oryzae infection, we identified a group of known rice
      miRNAs that were differentially expressed upon M. oryzae infection. They were
      further classified into three classes based on their expression patterns in the
      susceptible japonica line Lijiangxin Tuan Hegu and in the resistant line
      International Rice Blast Line Pyricularia-Kanto51-m-Tsuyuake that contains a
      single resistance gene locus, Pyricularia-Kanto 51-m (Pikm), within the
      Lijiangxin Tuan Hegu background. RNA-blot assay of nine of them confirmed
      sequencing results. Real-time reverse transcription-polymerase chain reaction
      assay showed that the expression of some target genes was negatively correlated
      with the expression of miRNAs. Moreover, transgenic rice plants overexpressing
      miR160a and miR398b displayed enhanced resistance to M. oryzae, as demonstrated
      by decreased fungal growth, increased hydrogen peroxide accumulation at the
      infection site, and up-regulated expression of defense-related genes. Taken
      together, our data indicate that miRNAs are involved in rice immunity against M.
      oryzae and that overexpression of miR160a or miR398b can enhance rice resistance
      to the disease. 

PMID- 24335509
TI  - Amyloplast-localized SUBSTANDARD STARCH GRAIN4 protein influences the size of
      starch grains in rice endosperm.
AB  - Starch is a biologically and commercially important polymer of glucose and is
      synthesized to form starch grains (SGs) inside amyloplasts. Cereal endosperm
      accumulates starch to levels that are more than 90% of the total weight, and most
      of the intracellular space is occupied by SGs. The size of SGs differs depending
      on the plant species and is one of the most important factors for industrial
      applications of starch. However, the molecular machinery that regulates the size
      of SGs is unknown. In this study, we report a novel rice (Oryza sativa) mutant
      called substandard starch grain4 (ssg4) that develops enlarged SGs in the
      endosperm. Enlargement of SGs in ssg4 was also observed in other starch
      accumulating tissues such as pollen grains, root caps, and young pericarps. The
      SSG4 gene was identified by map-based cloning. SSG4 encodes a protein that
      contains 2,135 amino acid residues and an amino-terminal amyloplast-targeted
      sequence. SSG4 contains a domain of unknown function490 that is conserved from
      bacteria to higher plants. Domain of unknown function490-containing proteins with
      lengths greater than 2,000 amino acid residues are predominant in photosynthetic
      organisms such as cyanobacteria and higher plants but are minor in
      proteobacteria. The results of this study suggest that SSG4 is a novel protein
      that influences the size of SGs. SSG4 will be a useful molecular tool for future
      starch breeding and biotechnology. 

PMID- 24335510
TI  - Expression and characterization of cynomolgus monkey cytochrome CYP3A4 in a novel
      human embryonic kidney cell-based mammalian system.
AB  - Cynomolgus monkeys are a commonly used species in preclinical drug discovery, and
      have high genetic similarity to humans, especially for the drug-metabolizing
      cytochrome P450s. However, species differences are frequently observed in the
      metabolism of drugs between cynomolgus monkeys and humans, and delineating these
      differences requires expressed CYPs. Toward this end, cynomolgus monkey CYP3A4
      (c3A4) was cloned and expressed in a novel human embryonic kidney 293-6E cell
      suspension system. Following the preparation of microsomes, the kinetic profiles
      of five known human CYP3A4 (h3A4) substrates (midazolam, testosterone,
      terfenadine, nifedipine, and triazolam) were determined. All five substrates were
      found to be good substrates of c3A4, although some differences were observed in
      the Km values. Overall, the data suggest a strong substrate similarity between
      c3A4 and h3A4. Additionally, c3A4 exhibited no activity against non-h3A4 probe
      substrates, except for a known human CYP2D6 substrate (bufuralol), which suggests
      potential metabolism of human cytochrome CYP2D6-substrates by c3A4. Ketoconazole
      and troleandomycin showed similar inhibitory potencies toward c3A4 and h3A4,
      whereas non-h3A4 inhibitors did not inhibit c3A4 activity. The availability of a
      c3A4 preparation, in conjunction with commercially available monkey liver
      microsomes, will support further characterization of the cynomolgus monkey as a
      model to assess CYP3A-dependent clearance and drug-drug interactions. 

PMID- 24335513
TI  - Strategies to Predict, Measure, and Improve Psychosocial Treatment Adherence.
AB  - Nonadherence to psychosocial and behavioral treatment is a significant public
      health problem that presents a barrier to recovery and effective treatment. An
      estimated 20% to 70% of individuals who initiate psychosocial mental health
      services discontinue treatment prior to clinicians' recommendations. Empirically
      supported, evidence-based, stand-alone or adjunctive psychosocial interventions
      treat an increasingly wide range of mental health conditions. A core assumption
      of most, if not all, interventions is that clients will fully and actively engage
      in the treatment protocol. Adherence to psychosocial treatment has received much
      less scientific attention, however, than adherence to medical treatment. Drawing
      extensively from existing research, this comprehensive review conceptualizes
      several types of psychosocial and behavioral treatment adherence, examines
      predictors of adherence to psychosocial treatment, summarizes measures of
      adherence, and describes existing interventions to enhance psychosocial treatment
      adherence.

PMID- 24335512
TI  - Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of
      RKIP and downregulation of bcl-2.
AB  - Treatment of recurrent and metastatic cervical cancer remains a challenge,
      especially in developing countries, which lack efficient screening programs. In
      recent years, artemisinin and its derivatives, such as dihydroartemisinin (DHA),
      which were traditionally used as anti-malarial agent, have been shown to inhibit
      tumor growth with low toxicity to normal cells. In this study, we investigated
      mechanisms underlying the anti-tumor effect of DHA in cervical cancer. We
      evaluated the role of DHA on the expression of bcl-2 and Raf kinase inhibitor
      protein (RKIP), which is a suppressor of metastasis. The MTT assay was used to
      compare the proliferation of untreated and DHA-treated Hela and Caski cervical
      cancer cells. Flow cytometry was used to determine the percentage of cells at
      each stage of the cell cycle in untreated and DHA-treated cells. We used RT-PCR
      and western blots to determine the expression of bcl-2 and RKIP mRNA and
      proteins. We evaluated the effect of DHA treatment in nude mice bearing Hela or
      Caski tumors. DHA-treated cells showed a time- and dose-dependent inhibition of
      proliferation and a significant increase in apoptosis. The expression of RKIP was
      significantly upregulated and the expression of bcl-2 was significantly
      downregulated in DHA-treated cells compared with control cells. DHA treatment
      caused (1) a significant inhibition of tumor growth and (2) a significant
      increase in the apoptotic index in nude mice bearing Hela or Caski tumors. Our
      data suggest that DHA inhibits cervical cancer growth via upregulation of RKIP
      and downregulation of bcl-2. 

PMID- 24335514
TI  - Neurobiology of mood-state shifts in bipolar disorder: a selective review and a
      hypothesis.
AB  - OBJECTIVE: Neuroimaging techniques have begun to elucidate the neurophysiology of
      bipolar disorder (BPD). Several features of BPD have hindered understanding of
      how mood-state changes are reflected in changes in brain physiology. Longitudinal
      studies have advantages in isolating state-related changes and in studying the
      instability, inherent in these disorders, that gives rise to pathological mood
      states. METHODS: To assess the state of the art in longitudinal neuroimaging
      studies in BPD, we conducted a literature review, searching MEDLINE for articles
      that included the key words bipolar disorder and magnetic resonance spectroscopy
      (MRS), magnetic resonance imaging (MRI), or emission tomography. The search was
      limited to studies with multiple subjects at two distinct and defined mood
      states. This search yielded eight MRS studies, four functional MRI studies, and
      three positron emission tomography studies. RESULTS: Although longitudinally
      designed studies allow for the isolation of biomarkers of mood state (including
      euthymia), the current literature is hampered by a lack of replication between
      studies. CONCLUSIONS: The current body of longitudinal BPD imaging studies is
      heterogeneous and incomplete, and does not lend itself to the construction of an
      explanatory model of mood-state transitions. Drawing on extant studies, we
      propose a hypothetical framework for future experiments combining multimodal
      imaging with a longitudinal study design.

PMID- 24335515
TI  - Report of ribosomal RNA methylase gene erm(B) in multidrug-resistant
      Campylobacter coli.
AB  - OBJECTIVES: Campylobacter is a major foodborne enteric pathogen and macrolides
      are the drug of choice for the clinical therapy of campylobacteriosis. Macrolide
      resistance among Campylobacter compromises clinical treatment, is associated with
      adverse health events and is a significant public health concern. Here, we report
      the first identification of a horizontally transferrable macrolide resistance
      mechanism in porcine Campylobacter coli ZC113 that is mediated by a ribosomal RNA
      methylase, Erm(B). METHODS: Horizontal transfer of a macrolide resistance
      determinant between C. coli and Campylobacter jejuni was performed by natural
      transformation. Whole-genome sequencing was initially used to identify the
      ribosomal methylase-encoding gene erm(B) in Campylobacter. Cloning of erm(B) into
      C. jejuni NCTC 11168 was performed to evaluate whether the erm(B) gene is
      responsible for high-level macrolide resistance in Campylobacter. RESULTS: The
      erm(B) gene was identified in ZC113, conferred high-level resistance to
      macrolides and was associated with a chromosomal multidrug-resistant genomic
      island (MDRGI). The MDRGI probably originated from Gram-positive bacteria and was
      horizontally transferred between C. coli and C. jejuni via natural
      transformation. Furthermore, the erm(B)-positive isolate ZC113 was resistant to
      all clinically important antibiotics used for treating campylobacteriosis and is
      essentially multidrug-resistant Campylobacter. CONCLUSIONS: To the best of our
      knowledge, this is the first report of a horizontally transferable macrolide
      resistance mechanism in thermophilic Campylobacter. Surveillance of erm(B) and
      its associated MDRGI in both C. coli and C. jejuni is urgently warranted.

PMID- 24335516
TI  - Clonality assessment of cutaneous B-cell lymphoid proliferations: a comparison of
      flow cytometry immunophenotyping, molecular studies, and immunohistochemistry/in
      situ hybridization and review of the literature.
AB  - Cutaneous lymphoid infiltrates are diagnostically challenging. Although ancillary
      techniques to assess clonality can help distinguish between reactive lymphoid
      hyperplasia and lymphoma, one of the most widely used techniques in
      hematopathology, flow cytometry immunophenotyping (FCI), has not been routinely
      applied to skin specimens. We performed FCI on 73 skin specimens from 67 patients
      clinically suspected of having a cutaneous B-cell lymphoma (CBCL) and compared
      the results with those obtained from immunoglobulin heavy chain (IGH) gene
      molecular studies (58 cases, primarily by polymerase chain reaction) and either
      immunohistochemistry (IHC) or in situ hybridization to evaluate for light chain
      restriction (22 and 2 cases, respectively). Sufficient quantity of CD45
      (leukocyte common antigen)-positive cells and staining quality were achieved in
      88% of cases by FCI, and clonality was detected in 68% of CBCLs versus molecular
      studies showing sufficient DNA quality in 74% and only 39% clonality detection,
      and interpretable/contributory IHC results in 84% of cases with 55% clonality
      detection. Clonality was documented more frequently in secondary rather than
      primary CBCLs by all 3 techniques. Therefore, FCI is feasible and appears to be
      more reliable than molecular studies or IHC/in situ hybridization for detecting
      clonality in CBCLs and can provide additional prognostically and therapeutically
      relevant information. The exception is cases with plasmacytic differentiation
      such as marginal zone lymphoma for which IHC might be a superior tool. We have
      also shown that a large subset of primary cutaneous follicle center lymphomas
      express CD10 and/or BCL2 by FCI. Recent advances in FCI beg the question of
      applicability to cutaneous T-cell and NK-cell lymphomas.

PMID- 24335517
TI  - Melanoma arising from a long-standing pigmented trichoblastoma: clinicopathologic
      study with complementary aCGH/mutational analysis.
AB  - Trichoblastoma is a benign cutaneous adnexal tumor, composed mostly of follicular
      germinative cells. Its pigmented variant is colonized by numerous dendritic
      melanocytes. So far, only one case in the literature describes a combination of
      trichoblastoma and melanoma. We report the case of a 62-year-old man who had a
      slow-growing mass of the left flank present since childhood. This 8-cm mass was
      surgically removed when it became ulcerated and associated with axillary lymph
      nodes. Histologically, this tumor was strictly dermal and composed of 2
      intermingled components. Large sheets of atypical, proliferating epithelioid
      cells predominated. Dispersed solid nests or cribriform epithelial islets encased
      in fibrous tissue were also seen. Some nests displayed a massive colonization by
      pigmented dendritic melanocytes. On immunohistochemical staining, the sheets of
      atypical cells expressed focally but strongly S100 protein, MelanA, HMB45, and
      MiTF. Epithelial structures diffusely expressed pancytokeratin AE1/AE3, KL1, and
      pleckstrin homology-like domain, family A, member 1. Based on these results, we
      diagnosed an intradermal melanoma, possibly developed from dendritic melanocytes
      colonizing a giant pigmented trichoblastoma. Direct sequencing of the melanoma
      revealed a rarely described NRAS mutation c.34G>T (G12C). Array comparative
      genomic hybridization displayed a complex profile somewhat divergent from
      standard melanoma profiles. The patient died of widespread metastatic disease 8
      months after initial diagnosis.

PMID- 24335518
TI  - Necrobiotic granulomatous tattoo reaction: report of an unusual case showing
      features of both necrobiosis lipoidica and granuloma annulare patterns.
AB  - The application of decorative tattoos to the skin is an ancient practice, which
      continues to be popular in the present day. Increasingly, a number of
      complications of tattoo application are recognized, including a diverse variety
      of cutaneous hypersensitivity reactions to tattoo pigments. Herein we describe an
      unusual case of a necrobiotic granulomatous tattoo reaction showing combined
      features of necrobiosis lipoidica and early granuloma annulare. The relevant
      literature is reviewed, and the practical significance of such unusual
      histological features as a part of the tattoo reaction is discussed.

PMID- 24335519
TI  - Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.
AB  - Eccrine nevus shows increase in number or size of eccrine glands, whereas hair
      follicle nevus is composed of densely packed normal vellus hairs, and eccrine
      pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous
      structures. No case with increased number of both eccrine glands and hair
      follicles only in the dermis has been previously reported. A 10-month-old girl
      presented with cutaneous hamartoma with overlying skin hyperpigmentation on her
      left hypochondrium since 3 months of age, in whom the lesion was completely
      excised. Histopathology demonstrated evidently increased number of both eccrine
      glands and hair follicles in the dermis with reactive hyperplasia of collagen
      fibers. No recurrence occurred after the tumor was completely excised. A term
      "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique
      lesion.

PMID- 24335520
TI  - Primary cutaneous carcinosarcomas: a morphological histogenetic concept
      revisited.
AB  - To present and define diagnostic criteria for primary cutaneous carcinosarcomas
      (CSs). Neoplasms of 6 patients with primary cutaneous CSs were retrospectively
      analyzed. A panel of histopathologic parameters and immunophenotypic expression
      of distinct markers of differentiation were investigated. All cases had medium-to
      poorly differentiated squamous cell carcinoma representing the epithelial
      component intermingled with a variable amount of malignant sarcomatous tissue
      proliferation. The authors identified 3 distinct morphological criteria for the
      diagnosis of primary cutaneous CSs with features of (1) a clearly defined dual
      neoplasm with explicit morphological characterization using histology and
      immunohistochemistry with distinct marker panels while, (2) metastases from
      distant sites and true collision neoplasms must be excluded, and (3) recognition
      of the neoplasm as a solid coherent proliferation with careful exclusion of
      sarcomatous stromal changes in the surrounding neoplasm stroma has to be assured.
      The low incidence of this entity and a plethora of different synonymous terms in
      the dermatopathologic literature often cause diagnostic problems and hamper the
      accurate comparative analysis of cases published previously. Herein, the authors
      propose defining criteria and a clearly defined morphological approach to
      contribute to more accurate dermatopathologic diagnoses and provide an
      unprecedented summary on this neoplastic entity.

PMID- 24335521
TI  - Eight new peptaibols from sponge-associated Trichoderma atroviride.
AB  - Eight new and four known peptaibols were isolated from a strain of the fungus,
      Trichoderma atroviride (NF16), which was cultured from an Axinellid sponge
      collected from the East Mediterranean coast of Israel. The structures of the pure
      compounds were determined using HRMS, MS/MS and one- and two-dimensional NMR
      measurements. The isolated compounds belong to the trichorzianines, a family of
      19-residue linear hydrophobic peptides containing a high proportion of alpha
      aminoisobutyric acid (Aib), an acetylated N-terminus and a C-terminal amino
      alcohol. These new peptaibols exhibited antimicrobial activity against
      environmental bacteria isolated from the Mediterranean coast of Israel. 

PMID- 24335522
TI  - New dimeric members of the phomoxanthone family: phomolactonexanthones A, B and
      deacetylphomoxanthone C isolated from the fungus Phomopsis sp.
AB  - Three new phomoxanthone compounds, phomolactonexanthones A (1), B (2) and
      deacetylphomoxanthone C (3), along with five known phomoxanthones, including
      dicerandrol A (4), dicerandrol B (5), dicerandrol (6), deacetylphomoxanthone B
      (7) and penexanthone A (8), were isolated in the metabolites of the fungus
      Phomopsis sp. HNY29-2B, which was isolated from the mangrove plants. The
      structures of compounds 1-3 were established on the basis of spectroscopic
      analysis. All compounds were evaluated against four human cancer cell lines
      including human breast MDA-MB-435, human colon HCT-116, human lung Calu-3 and
      human liver Huh7 by MTT assay. The compounds 4, 5, 7 and 8 showed cytotoxic
      activities against tested cancer cell lines (IC50 < 10 MUM).

PMID- 24335523
TI  - The effect of 17alpha-ethynylestradiol on steroidogenesis and gonadal cytokine
      gene expression is related to the reproductive stage in marine hermaphrodite
      fish.
AB  - Pollutants have been reported to disrupt the endocrine system of marine animals,
      which may be exposed through contaminated seawater or through the food chain.
      Although 17alpha-ethynylestradiol (EE2), a drug used in hormone therapies, is
      widely present in the aquatic environment, current knowledge on the sensitivity
      of marine fish to estrogenic pollutants is limited. We report the effect of the
      dietary intake of 5 ug EE2/g food on different processes of testicular
      physiology, ranging from steroidogenesis to pathogen recognition, at both pre
      spermatogenesis (pre-SG) and spermatogenesis (SG) reproductive stages, of
      gilthead seabream (Sparus aurata L.), a marine hermaphrodite teleost. A
      differential effect between pre-SG and SG specimens was detected in the sex
      steroid serum levels and in the expression profile of some steroidogenic-relevant
      molecules, vitellogenin, double sex- and mab3-related transcription factor 1 and
      some hormone receptors. Interestingly, EE2 modified the expression pattern of
      some immune molecules involved in testicular physiology. These differences
      probably reflect a developmental adjustment of the sensitivity to EE2 in the
      gilthead seabream gonad.

PMID- 24335524
TI  - The effect of eating sea cucumber jelly on Candida load in the oral cavity of
      elderly individuals in a nursing home.
AB  - We conducted a double-blind randomized controlled study of elderly individuals in
      a nursing home to investigate the effect of the consumption of jelly containing
      sea cucumber on their oral Candida load. The jelly contained a hydrolysate of the
      sea cucumber Stichopus japonicus, which contained triterpene glycosides called
      holotoxins. The holotoxins worked as a fungicide, and their minimum inhibitory
      concentrations for Candida albicans were 7 ug/mL. Eight individuals in the
      nursing home took the sea cucumber jelly for a week and their oral Candida were
      counted before and after the intervention. Nine individuals took a control jelly
      without S. japonicus. The sea cucumber jelly showed inhibitory effects on the
      oral Candida. Thus, daily consumption of the S. japonicus jelly has the potential
      to reduce the oral Candida load in the elderly in nursing homes. 

PMID- 24335525
TI  - Biosynthesis of polyunsaturated fatty acids in the oleaginous marine diatom
      Fistulifera sp. strain JPCC DA0580.
AB  - Studies of polyunsaturated fatty acid (PUFA) biosynthesis in microalgae are of
      great importance for many reasons, including the production of biofuel and
      variable omega 3-long chain PUFAs. The elucidation of the PUFA biosynthesis
      pathway is necessary for bioengineering to increase or decrease PUFA content in
      certain microalgae. In this study, we identified the PUFA synthesis pathway in
      the oleaginous marine diatom, Fistulifera sp. strain JPCC DA0580, a promising
      candidate for biodiesel production. The data revealed not only the presence of
      the desaturases and elongases involved in eicosapentaenoic acid (EPA) synthesis,
      but also the unexpected localization of omega3-desaturase expression in the
      chloroplast. This suggests that this microalga might perform the final step of
      EPA synthesis in the chloroplast and not in the endoplasmic reticulum (ER) like
      other diatoms. The detailed fatty acid profile suggests that the EPA was
      synthesized only through the omega6-pathway in this strain, which was also
      different from other diatoms. Finally, the transcriptome analysis demonstrated an
      overall down-regulation of desaturases and elongases over incubation time. These
      genetic features might explain the decrease of PUFA percentage over incubation
      time in this strain. The important insights into metabolite synthesis acquired
      here will be useful for future metabolic engineering to control PUFA content in
      this diatom. 

PMID- 24335526
TI  - Diamond squid (Thysanoteuthis rhombus)-derived chondroitin sulfate stimulates
      bone healing within a rat calvarial defect.
AB  - Chondroitin sulfate (CS) has been suggested to be involved in bone formation and
      mineralization processes. A previous study showed that squid-derived CS (sqCS)
      has osteoblastogenesis ability in cooperation with bone morphogenetic protein
      (BMP)-4 in vitro. However, in vivo, osteogenic potential has not been verified.
      In this study, we created a critical-sized bone defect in the rat calvaria and
      implanted sqCS-loaded gelatin hydrogel sponges (Gel) into the defect with or
      without BMP-4 (CS/BMP/Gel and CS/Gel, respectively). At 15 weeks, bone repair
      rate of CS/Gel-treated defects and CS/BMP/Gel-treated defects were 47.2% and
      51.1%, respectively, whereas empty defects and defects with untreated sponges
      showed significantly less bone ingrowth. The intensity of von Kossa staining of
      the regenerated bone was less than that of the original one. Mineral apposition
      rates at 9 to 10 weeks were not significantly different between all treatment
      groups. Although bone repair was not completed, sqCS stimulated bone regeneration
      without BMP-4 and without external mesenchymal cells or preosteoblasts.
      Therefore, sqCS is a promising substance for promotion of osteogenesis. 

PMID- 24335527
TI  - High-resolution magnetic resonance microscopy and diffusion tensor imaging to
      assess brain structural abnormalities in the murine mucopolysaccharidosis VII
      model.
AB  - High-resolution microscopic magnetic resonance imaging (MUMRI) and diffusion
      tensor imaging (DTI) were performed to characterize brain structural
      abnormalities in a mouse model of mucopolysaccharidosis type VII (MPS VII).
      Microscopic magnetic resonance imaging demonstrated a decrease in the volume of
      anterior commissure and corpus callosum and a slight increase in the volume of
      the hippocampus in MPS VII versus wild-type mice. Diffusion tensor imaging
      indices were analyzed in gray and white matter. In vivo and ex vivo DTI
      demonstrated significantly reduced fractional anisotropy in the anterior
      commissure, corpus callosum, external capsule, and hippocampus in MPS VII versus
      control brains. Significantly increased mean diffusivity was also found in the
      anterior commissure and corpus callosum from ex vivo DTI. Significantly reduced
      linear anisotropy was observed from the hippocampus from in vivo DTI, whereas
      significantly decreased planar anisotropy and spherical anisotropy were observed
      in the external capsule from only ex vivo DTI. There were corresponding
      morphologic differences in the brains of MPS VII mice by hematoxylin and eosin
      staining. Luxol fast blue staining demonstrated less intense staining of the
      corpus callosum and external capsule; myelin abnormalities in the corpus callosum
      were also demonstrated quantitatively in toluidine blue-stained sections and
      confirmed by electron microscopy. These results demonstrate the potential for
      MUMRI and DTI for quantitative assessment of brain pathology in murine models of
      brain diseases. 

PMID- 24335528
TI  - Sox10 nuclear immunostaining lacks diagnostic utility for CNS granular cell
      tumors.

PMID- 24335529
TI  - Enhanced human immunodeficiency virus Type 1 expression and neuropathogenesis in
      knockout mice lacking Type I interferon responses.
AB  - The roles of Type I interferon (IFN) in human immunodeficiency virus Type 1 (HIV
      1) neuropathogenesis are poorly understood; both protective and deleterious
      effects of IFN signaling have been described. We used genetically modified mice
      deficient in the Type I IFN receptor (IFNRKO) to analyze the progress of HIV-1
      brain infection and neuropathogenesis in the absence of IFN signaling. IFNRKO and
      wild-type (WT) mice on the 129xSv/Ev or C57BL/6 strain backgrounds were infected
      systemically with EcoHIV, a chimeric HIV-1 that productively infects mice. IFNRKO
      mice showed higher HIV-1 expression in spleen and peritoneal macrophages and
      greater virus infiltration into the brain compared to WT mice. Neuropathogenesis
      was studied by histopathological, immunohistochemical, immunofluorescence, and
      polymerase chain reaction analyses of brain tissues after the virus was
      inoculated into the brain by stereotaxic intracerebral injection. Both IFNRKO and
      WT mice showed readily detectable HIV-1 and brain lesions, including microglial
      activation, astrocytosis, and increased expression of genes coding for
      inflammatory cytokines and chemokines typical of human HIV-1 brain disease.
      Parameters of HIV-1 neuropathogenesis, including HIV-1 expression in
      microglia/macrophages, were significantly greater in IFNRKO than in WT mice. Our
      results show unequivocally that Type I IFN signaling and responses limit HIV-1
      infection and pathogenesis in the brains of mice. 

PMID- 24335530
TI  - Modulation of hippocampal neuroplasticity by Fas/CD95 regulatory protein 2
      (Faim2) in the course of bacterial meningitis.
AB  - Fas-apoptotic inhibitory molecule 2 (Faim2) is a neuron-specific membrane protein
      and a member of the evolutionary conserved lifeguard apoptosis regulatory gene
      family. Its neuroprotective effect in acute neurological diseases has been
      demonstrated in an in vivo model of focal cerebral ischemia. Here we show that
      Faim2 is physiologically expressed in the human brain with a changing pattern in
      cases of infectious meningoencephalitis.In Faim2-deficient mice, there was
      increased caspase-associated hippocampal apoptotic cell death and an increased
      extracellular signal-regulated kinase pattern during acute bacterial meningitis
      induced by subarachnoid infection with Streptococcus pneumoniae type 3 strain.
      However, after rescuing the animals by antibiotic treatment, Faim2 deficiency led
      to increased hippocampal neurogenesis at 7 weeks after infection. This was
      associated with improved performance of Faim2-deficient mice compared to wild
      type littermates in the Morris water maze, a paradigm for hippocampal spatial
      learning and memory. Thus, Faim2 deficiency aggravated degenerative processes in
      the acute phase but induced regenerative processes in the repair phase of a mouse
      model of pneumococcal meningitis. Hence, time-dependent modulation of
      neuroplasticity by Faim2 may offer a new therapeutic approach for reducing
      hippocampal neuronal cell death and improving cognitive deficits after bacterial
      meningitis. 

PMID- 24335531
TI  - Argyrophilic grains are reliable disease-specific features of corticobasal
      degeneration.
AB  - Argyrophilic grains are discrete punctate structures that bind to silver stains;
      they can be observed within the neuropil of the limbic system, particularly in
      the elderly. It has been reported that argyrophilic grains are more frequent in
      patients with corticobasal degeneration (CBD) compared with the elderly
      population in general. To determine the frequency and significance of
      argyrophilic grains in CBD, we examined the temporal lobes from 35 patients with
      autopsy-proven CBD (mean age, 69.1 years) and 28 patients with argyrophilic grain
      disease (mean age, 95.7 years). Grain distributions and densities were evaluated
      semiquantitatively using Gallyas-Braak stains and immunohistochemistry with AT8
      and RD4 antibodies. Argyrophilic grains were observed in all CBD cases (100%)
      despite a lower average age at death in this population. We also observed the
      following features that were specific to argyrophilic grains in CBD: 1) grains
      were likely to be widespread throughout the temporal lobe, 2) grains were
      consistently found with abundant argyrophilic threads, and 3) the ultrastructure
      of grains contained paired helical filaments with a periodicity of 120 to 130 nm.
      In conclusion, we confirm that argyrophilic grains in CBD are specifically
      related to the 4-repeat tau pathology of CBD and are not simply a result of
      aging. 

PMID- 24335532
TI  - Glial and neuronal tau pathology in tauopathies: characterization of disease
      specific phenotypes and tau pathology progression.
AB  - Tauopathies are degenerative diseases characterized by the accumulation of
      phosphorylated tau in neurons and glial cells. With some exceptions, tau deposits
      in neurons are mainly manifested as pretangles and tangles unrelated to the
      tauopathy. It is thought that abnormal tau deposition in neurons occurs following
      specific steps, but little is known about the progression of tau pathology in
      glial cells in tauopathies. We compared tau pathology in different astrocyte
      phenotypes and oligodendroglial inclusions with that in neurons in a large series
      of tauopathies, including progressive supranuclear palsy, corticobasal
      degeneration, argyrophilic grain disease, Pick disease, frontotemporal lobar
      degenerations (FTLD) associated with mutations in the tau gene, globular glial
      tauopathy (GGT), and tauopathy in the elderly. Our findings indicate that disease
      specific astroglial phenotypes depend on i) the primary amino acid sequence of
      tau (mutated tau, 3Rtau, and 4Rtau); ii) phospho-specific sites of tau
      phosphorylation, tau conformation, tau truncation, and ubiquitination in that
      order (which parallel tau modifications related to pretangle and tangle stages in
      neurons); and iii) modifications of the astroglial cytoskeleton. In contrast to
      astrocytes, coiled bodies in oligodendrocytes have similar characteristics
      whatever the tauopathy, except glial globular inclusions in GGT, and coiled
      bodies and globular oligodendroglial inclusions in FTLD-tau/K317M. These
      observations indicate that tau pathology in glial cells largely parallels, but is
      not identical to, that in neurons in many tauopathies. 

PMID- 24335533
TI  - Progressive neurodegeneration after experimental brain trauma: association with
      chronic microglial activation.
AB  - Recent clinical studies indicate that traumatic brain injury (TBI) produces
      chronic and progressive neurodegenerative changes leading to late neurologic
      dysfunction, but little is known about the mechanisms underlying such changes.
      Microglial-mediated neuroinflammationis an important secondary injury mechanism
      after TBI. In human studies, microglial activation has been found to persist for
      many years after the initial brain trauma, particularly after moderate to severe
      TBI. In the present study, adult C57Bl/6 mice were subjected to single moderate
      level controlled cortical impact and were followed up by longitudinal T2-weighted
      magnetic resonance imaging in combination with stereologic histologic assessment
      of lesion volume expansion, neuronal loss, and microglial activation for up to 1
      year after TBI. Persistent microglial activation was observed in the injured
      cortex through 1 year after injury and was associated with progressive lesion
      expansion, hippocampal neurodegeneration, and loss of myelin. Notably, highly
      activated microglia that expressed major histocompatibility complex class II
      (CR3/43), CD68, and NADPH oxidase (NOX2) were detected at the margins of the
      expanding lesion at 1 year after injury; biochemical markers of neuroinflammation
      and oxidative stress were significantly elevated at this time point. These data
      support emerging clinical TBI findings and provide a mechanistic link between TBI
      induced chronic microglial activation and progressive neurodegeneration.

PMID- 24335534
TI  - Molecular dissection of the VHL gene in solitary capillary hemangioblastoma of
      the central nervous system.
AB  - Capillary hemangioblastomas (HGBs) of the CNS occur either sporadically or as
      part of the von Hippel-Lindau (VHL) syndrome. Molecular characterizations of the
      VHL gene in sporadic HGBs at the somatic level have been limited to date. We
      investigated the VHL gene in 57 patients most of whom (55 [96%] of 57) had a
      solitary CNS HGB at the time of surgery. Tissues from 23 HGBs of these patients
      (2 VHL related and 21 unrelated) were also investigated at genetic and epigenetic
      levels. Two of the 51 patients with apparently sporadic HGBs and no additional
      evidence of VHL (~4%) were found to have a germline VHL gene mutation; both of
      these patients subsequently developed evidence of VHL syndrome. Somatic VHL gene
      mutations were found in 11 (52%) of the 21 non-VHL-related cases. A germline
      mutation was identified in 5 (84%) of 6 VHL-associated HGBs; double gene
      inactivation was observed in tumor tissue from VHL syndrome patients. Seven
      different previously unreported VHL gene alterations (6 somatic and 1 germline)
      were identified; double hits were identified in 7 (12%) of 57 cases. Our findings
      confirm the usefulness of VHL gene analysis at the germline level in patients who
      present with apparently solitary HGB. Moreover, the genetic and epigenetic VHL
      gene investigations performed support a key role for functional alterations of
      the VHL gene in sporadic neuraxial HGB. 

PMID- 24335535
TI  - Neuropathologic heterogeneity does not impair florbetapir-positron emission
      tomography postmortem correlates.
AB  - Neuropathologic heterogeneity is often present among Alzheimer disease (AD)
      patients. We sought to determine whether amyloid imaging measures of AD are
      affected by concurrent pathologies. Thirty-eight clinically and pathologically
      defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV
      45) positron emission tomography (PET) imaging during life and postmortem
      histological beta-amyloid quantification and neuropathologic examination were
      assessed. AD patients were divided on the basis of concurrent pathologies,
      including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n =
      27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5),
      and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more
      than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid
      imaging signal (SUVr) and immunohistochemical beta-amyloid load were analyzed in
      6 cortical regions of interest. All AD subgroups had strong and significant
      correlations between SUVr and histological beta-amyloid measures (p MU 0.001).
      All AD subgroups had significantly greater amyloid measures versus nondemented
      patients, and mean amyloid measures did not significantly differ between AD
      subgroups. When comparing AD cases with and without each pathology, AD cases with
      LBs had significantly lower SUVr measures versus AD cases without LBs (p =
      0.002); there were no other paired comparison differences. These findings
      indicate that florbetapir-PET imaging is not confounded by neuropathological
      heterogeneity within AD. 

PMID- 24335536
TI  - A Q-methodology study of parental understandings of infant immunisation:
      Implications for health-care advice.
AB  - This study used Q-methodology to explore systematically parental judgements about
      infant immunisation. A total of 45 parents completed a 31-statement Q-sort. Data
      were collected after vaccination in general practitioner practices or a private
      day nursery. Q factor analysis revealed four distinct viewpoints: a duty to
      immunise based on medical benefits, child-orientated protection based on parental
      belief, concern and distress and surprise at non-compliance. Additionally, there
      was a common view among parents that they did not regret immunising their
      children. Implications of these results are discussed in terms of health-care
      policy and future research. 

PMID- 24335537
TI  - Illness perceptions in patients with somatoform disorders: examining the role of
      comorbidity.
AB  - We examined the role of comorbidity in models that use the illness perceptions of
      patients with somatoform disorders to explain their outcomes. A total of 138
      primary care patients with somatoform disorders completed the Patient Health
      Questionnaire and Brief Illness Perception Questionnaire and rated their general
      health status. Medical comorbidity was rated by the general practitioner.
      Patients' illness perceptions were consistently related to their outcomes
      independent of medical and psychological comorbidity in our models. At the same
      time, inclusion of comorbidity enhanced our models, revealing differences in the
      relevance of the specific comorbidity depending on the outcome measure.

PMID- 24335538
TI  - The clinical impact of the sum of the maximum standardized uptake value on the
      pretreatment with F-FDG-PET/CT in small-cell lung cancer.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical significance of
      the sum of the maximum standardized uptake value (sumSUVmax) on pretreatment
      positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in newly
      diagnosed small-cell lung cancer (SCLC). METHODS: We retrospectively analyzed 145
      SCLC patients from March 2005 to June 2013 who underwent pretreatment (18)F-FDG
      PET/CT. The sumSUVmax was assessed in all malignant lesions up to a maximum of 5
      lesions and a maximum of 2 lesions per organ according to RECIST 1.1. RESULTS: A
      significant difference was found between the low and high sumSUVmax groups (low
      vs. high sumSUVmax, 91.5 vs. 77.3%; p = 0.018) in the response rate (RR)
      following frontline platinum-based chemotherapy. The group with low sumSUVmax
      showed significantly better overall survival (OS; p < 0.001) as well as better
      progression-free survival (PFS; p < 0.001) compared with the group with high
      sumSUVmax. Moreover, multivariate analysis revealed that a high sumSUVmax alone
      was an independent poor prognostic factor for OS (hazard ratio 2.676; 95%
      confidence interval, 1.674-4.277; p < 0.001). CONCLUSIONS: This study showed that
      the sumSUVmax adopted from RECIST 1.1 on pretreatment (18)F-FDG PET/CT was
      significantly correlated with response to treatment, OS, and PFS in patients with
      SCLC.

PMID- 24335539
TI  - Spinal cord injury after blunt cervical spine trauma: correlation of soft-tissue
      damage and extension of lesion.
AB  - BACKGROUND AND PURPOSE: In patients with spinal cord injury after blunt trauma,
      several studies have observed a correlation between neurologic impairment and
      radiologic findings. Few studies have been performed to correlate spinal cord
      injury with ligamentous injury. The purpose of this study was to retrospectively
      evaluate whether ligamentous injury or disk disruption after spinal cord injury
      correlates with lesion length. MATERIALS AND METHODS: We retrospectively reviewed
      108 patients diagnosed with traumatic spinal cord injury after cervical trauma
      between 1990-2011. Plain films, CT, and MR imaging were performed on patients and
      then reviewed for this study. MR imaging was performed within 96 hours after
      cervical trauma for all patients. Data regarding ligamentous injury, disk injury,
      and the extent of the spinal cord injury were collected from an adequate number
      of MR images. We evaluated anterior longitudinal ligaments, posterior
      longitudinal ligaments, and the ligamentum flavum. Length of lesion, disk
      disruption, and ligamentous injury association, as well as the extent of the
      spinal cord injury were statistically assessed by means of univariate analysis,
      with the use of nonparametric tests and multivariate analysis along with linear
      regression. RESULTS: There were significant differences in lesion length on T2
      weighted images for anterior longitudinal ligaments, posterior longitudinal
      ligaments, and ligamentum flavum in the univariate analysis; however, when this
      was adjusted by age, level of injury, sex, and disruption of the soft tissue
      evaluated (disk, anterior longitudinal ligaments, posterior longitudinal
      ligaments, and ligamentum flavum) in a multivariable analysis, only ligamentum
      flavum showed a statistically significant association with lesion length.
      Furthermore, the number of ligaments affected had a positive correlation with the
      extension of the lesion. CONCLUSIONS: In cervical spine trauma, a specific
      pattern of ligamentous injury correlates with the length of the spinal cord
      lesion in MR imaging studies. Ligamentous injury detected by MR imaging is not a
      dynamic finding; thus it proved to be useful in predicting neurologic outcome in
      patients for whom the MR imaging examination was delayed.

PMID- 24335540
TI  - Cerebral veins-why functional MR imaging is worth the trouble.

PMID- 24335541
TI  - DWI reversal is associated with small infarct volume in patients with TIA and
      minor stroke.
AB  - BACKGROUND AND PURPOSE: More than half of patients with TIA/minor stroke have
      ischemic lesions on early DWI, which represent irreversibly damaged tissue. The
      presence and volume of DWI lesions predict early deterioration in this
      population. We aimed to study the rate and implications of DWI reversal in
      patients with TIA/minor stroke. MATERIALS AND METHODS: Patients with TIA/minor
      stroke were prospectively enrolled and imaged within 24 hours of onset. Patients
      were followed for 3 months with repeat MR imaging either at day 30 or 90.
      Baseline DWI/PWI and follow-up FLAIR final infarct volumes were measured.
      RESULTS: Of 418 patients included, 55.5% had DWI and 37% had PWI (time-to-peak of
      the impulse response >=2 seconds' delay) lesions at baseline. The median time
      from symptom onset to baseline and follow-up imaging was 13.4 (interquartile
      range, 12.7) and 78.73 hours (interquartile range, 60.2), respectively. DWI
      reversal occurred in 5.7% of patients. The median DWI lesion volume was
      significantly smaller in those with reversal (0.26 mL, interquartile range = 0.58
      mL) compared with those without (1.29 mL, interquartile range = 3.6 mL, P =
      .002); 72.7% of DWI reversal occurred in cortically based lesions. Concurrent
      tissue hypoperfusion (time-to-peak of the impulse response >=2 seconds) was seen
      in 36.4% of those with DWI reversal versus 62.4% without (P = .08). DWI reversal
      occurred in 3.3% of patients with penumbral patterns (time-to-peak of the impulse
      response >=6 seconds - DWI) > 0 and in 6.8% of those without penumbral patterns
      (P = .3). The severity of hypoperfusion, defined as greater prolongation of time
      to-peak of the impulse response (>=2, >=4, >=6, >=8 seconds), did not affect the
      likelihood of DWI reversal (linear trend, P = .147). No patient with DWI reversal
      had an mRS score of >=2 at 90 days versus 18.2% of those without reversal (P =
      .02). CONCLUSIONS: DWI reversal is uncommon in patients with TIA/minor stroke and
      is more likely to occur in those with smaller baseline lesions. DWI reversal
      should not have a significant effect on the accuracy of penumbra definition.

PMID- 24335542
TI  - Acute basilar artery occlusion: outcome of mechanical thrombectomy with Solitaire
      stent within 8 hours of stroke onset.
AB  - BACKGROUND AND PURPOSE: Mechanical thrombectomy with a stent retriever applied
      shortly after symptom onset could increase good functional outcomes and improve
      survival in patients with acute basilar artery occlusion, but this has not yet
      been studied. This study evaluated the efficacy and safety of mechanical
      thrombectomy with a Solitaire stent within 8 hours of stroke onset in patients
      with acute basilar artery occlusion. MATERIALS AND METHODS: We analyzed 25
      consecutive patients with acute basilar artery occlusion who were treated with
      mechanical thrombectomy by use of the Solitaire stent within 8 hours of stroke
      symptom onset. Successful recanalization was defined as TICI grade 2b or 3. Good
      outcome was defined as mRS score of 0-2 at 3 months. Clinical and radiologic data
      in patients with good outcomes were compared with those with poor outcomes.
      RESULTS: Successful recanalization was achieved in 96% (24/25) of patients, and
      48% (12/25) of patients had good outcomes. Eighty-eight percent (22/25) of
      patients survived to 3 months. The median NIHSS score on admission was
      significantly lower in patients with good outcomes than in those with poor
      outcomes (9.5 versus 14, P = .005). Procedure-related complications occurred in 2
      patients (8%). No symptomatic intracerebral hemorrhages occurred. CONCLUSIONS:
      The current study suggests that mechanical thrombectomy by use of a Solitaire
      stent within 8 hours of stroke onset increases good outcomes and improves
      survival in patients with acute basilar artery occlusion.

PMID- 24335543
TI  - Role of EPI-FLAIR in patients with acute stroke: a comparative analysis with
      FLAIR.
AB  - BACKGROUND AND PURPOSE: Further improvement in acquisition speed is needed, if MR
      imaging is to compete with CT for evaluation of patients with acute ischemic
      stroke. The purpose of this study was to evaluate the feasibility of implementing
      an echo-planar fluid-attenuated inversion recovery (EPI-FLAIR) sequence into an
      acute MR stroke protocol with potential reduction in scan time and to compare the
      results with conventional FLAIR images. MATERIALS AND METHODS: Fifty-two patients
      (28 men and 24 women; age range, 32-96 years) with acute ischemic stroke were
      prospectively evaluated with an acute stroke MR protocol, which included both
      conventional FLAIR and EPI-FLAIR imaging with integration of parallel
      acquisition. The image acquisition time was 52 seconds for EPI-FLAIR and 3
      minutes for conventional FLAIR. FLAIR and EPI-FLAIR studies were assessed by 2
      observers independently for image quality and conspicuity of hyperintensity in
      correlation with DWI and were rated as concordant or discordant. Coregistered
      FLAIR and EPI-FLAIR images were evaluated for signal intensity ratio of the DWI
      positive lesion to contralateral normal white matter. RESULTS: An estimated 96%
      of all FLAIR and EPI-FLAIR studies were rated of diagnostic image quality by both
      observers, with interobserver agreements of kappa = 0.82 and kappa = 0.63 for
      FLAIR and EPI-FLAIR, respectively. In 36 (95%) of 38 patients with acute
      infarction, FLAIR and EPI-FLAIR were rated concordant regarding DWI lesion. The
      mean +/- standard deviation of the signal intensity ratio values on EPI-FLAIR and
      FLAIR for DWI-positive lesions were 1.28 +/- 0.16 and 1.25 +/- 0.17, respectively
      (P = .47), and demonstrated significant correlation (r = 0.899, z value = 8.677,
      P < .0001). CONCLUSIONS: In patients with acute stroke, EPI-FLAIR is feasible
      with comparable qualitative and quantitative results to conventional FLAIR and
      results in reduced acquisition time.

PMID- 24335544
TI  - Temporary solitaire stent-assisted coiling: a technique for the treatment of
      acutely ruptured wide-neck intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Wide-neck intracranial aneurysms in patients with acute
      SAH are often challenging lesions to treat by neurosurgical and endovascular
      approaches. The aim of this study was to investigate the feasibility, safety, and
      efficacy of the use of temporary Solitaire AB stent-assisted technique with
      coiling for the treatment of acutely ruptured wide-neck aneurysms without
      perioperative antiplatelet therapy. MATERIALS AND METHODS: A retrospective review
      of our endovascular data base identified all patients treated in the acute phase
      with a temporary stent-assisted technique by use of a fully resheathable
      Solitaire AB stent and coiling. One-year clinical and angiographic outcomes were
      evaluated. RESULTS: Eight patients (5 women and 3 men; mean age, 57.5 years) with
      8 ruptured wide-neck aneurysms were treated. There were 3 complications without
      clinical impact. Postoperative complete occlusion was achieved in 5 aneurysms,
      and 3 had a neck remnant. Three patients had an mRS score of 0, and 1 an mRS
      score of 3. Among the 4 patients admitted with a World Federation of Neurological
      Societies grade of V, 1 died, 1 improved to an mRS score of 1, and the other 2
      achieved mRS scores of 4 and 5. Five had a stable occlusion, and 2 of the 3
      incompletely occluded aneurysms underwent recanalization. CONCLUSIONS: In this
      small series, temporary placement of the Solitaire AB stent during coiling was a
      feasible and effective treatment for acutely ruptured wide-neck aneurysms. This
      technique, avoiding the need for perioperative antiplatelet therapy, could be a
      valuable option for the treatment of such lesions when the balloon remodeling
      technique is either not an option or unsuccessful.

PMID- 24335545
TI  - Attitudes about medical malpractice: an American Society of Neuroradiology
      survey.
AB  - SUMMARY: The concern over medicolegal liability is pervasive among physicians. We
      sought, through an email survey to the members of the ASNR, to assess the
      experience with and attitudes about the medicolegal environment among
      neuroradiologists. Of 4357 physicians surveyed, 904 answered at least 1 of the
      questions in the survey; 449 of 904 (49.7%) had been sued: 180 (44.9%) had been
      sued once, 114 (28.4%) twice, 60 (15.0%) 3 times, and 47 (11.7%) more than 3
      times. The payouts for suits were most commonly in the $50,000 to $150,000 range,
      except for interventional neuroradiologists, in whom the most common value was
      $600,000 to $1,200,000. Only 9 of 481 (1.9%) of suits returned a plaintiff
      verdict. Despite reported outcomes that favored physicians with respect to cases
      being dropped (270/481 = 56.1%), settled without a payment (11/481 = 2.3%), or a
      defense verdict (46/481 = 9.6), most respondents (81.1%, 647/798) believed that
      the medicolegal system was weighted toward plaintiffs. More than half of the
      neuroradiologists (55.2%, 435/787) reported being mildly to moderately concerned,
      and 19.1% (150/787) were very or extremely concerned about being sued.

PMID- 24335546
TI  - Quantitative cerebral perfusion imaging in children and young adults with
      Moyamoya disease: comparison of arterial spin-labeling-MRI and H(2)[(15)O]-PET.
AB  - BACKGROUND AND PURPOSE: Cerebral perfusion assessment is important in the
      preoperative evaluation and postoperative follow-up of patients with Moyamoya
      disease. The objective of this study was to evaluate the correlation of
      quantitative CBF measurements performed with arterial spin-labeling-MR imaging
      and H2[(15)O]-PET in children and young adults with Moyamoya disease. MATERIALS
      AND METHODS: Thirteen children and young adults (8 female patients; age, 9.7 +/-
      7.1 years; range, 1-23 years) with Moyamoya disease underwent cerebral perfusion
      imaging with H2[(15)O]-PET (Discovery STE PET/CT, 3D Fourier rebinning filtered
      back-projection, 128 * 128 * 47 matrix, 2.34 * 2.34 * 3.27 mm(3) voxel spacing)
      and arterial spin-labeling (3T scanner, 3D pulsed continuous arterial spin
      labeling sequence, 32 axial sections, TR = 5.5 seconds, TE = 25 ms, FOV = 24 cm,
      128 * 128 matrix, 1.875 * 1.875 * 5 mm(3) voxel spacing) within less than 2 weeks
      of each other. Perfusion of left and right anterior cerebral artery, MCA, and
      posterior cerebral artery territories was qualitatively assessed for arterial
      spin-labeling-MR imaging and H2[(15)O]-PET by 2 independent readers by use of a 3
      point-Likert scale. Quantitative correlation of relative CBF with cerebellar
      normalization between arterial spin-labeling-MR imaging and H2[(15)O]-PET was
      evaluated in a volume-based approach for each vascular territory after 3D image
      coregistration. RESULTS: Interreader agreement was good (kappa = 0.67-0.69), and
      strong and significant correlations were found between arterial spin-labeling-MR
      imaging and H2[(15)O]-PET for both qualitative perfusion scoring (rho = 0.77; P <
      .001) and quantitative perfusion assessment of relative CBF with cerebellar
      normalization (r = 0.67, P < .001). CONCLUSIONS: In children and young adults
      with Moyamoya disease, quantitative evaluation of CBF is possible with the use of
      arterial spin-labeling-MR imaging without ionizing radiation or contrast
      injection with a good correlation to H2[(15)O]-PET after cerebellar
      normalization.

PMID- 24335547
TI  - Left hemisphere diffusivity of the arcuate fasciculus: influences of autism
      spectrum disorder and language impairment.
AB  - BACKGROUND AND PURPOSE: There has been much discussion whether brain
      abnormalities associated with specific language impairment and autism with
      language impairment are shared or are disorder specific. Although white matter
      tract abnormalities are observed in both specific language impairment and autism
      spectrum disorders, the similarities and differences in the white matter
      abnormalities in these 2 disorders have not been fully determined. MATERIALS AND
      METHODS: Diffusion tensor imaging diffusion parameters of the arcuate fasciculus
      were measured in 14 children with specific language impairment as well as in 16
      children with autism spectrum disorder with language impairment, 18 with autism
      spectrum disorder without language impairment, and 25 age-matched typically
      developing control participants. RESULTS: Language impairment and autism spectrum
      disorder both had (elevating) main effects on mean diffusivity of the left
      arcuate fasciculus, initially suggesting a shared white matter substrate
      abnormality. Analysis of axial and radial diffusivity components, however,
      indicated that autism spectrum disorder and language impairment differentially
      affect white matter microstructural properties, with a main effect of autism
      spectrum disorder on axial diffusivity and a main effect of language impairment
      on radial diffusivity. CONCLUSIONS: Although white matter abnormalities appear
      similar in language impairment and autism spectrum disorder when examining broad
      white matter measures, a more detailed analysis indicates different mechanisms
      for the white matter microstructural anomalies associated with language
      impairment and autism spectrum disorder.

PMID- 24335548
TI  - Subcortical deep gray matter pathology in patients with multiple sclerosis is
      associated with white matter lesion burden and atrophy but not with cortical
      atrophy: a diffusion tensor MRI study.
AB  - BACKGROUND AND PURPOSE: The association between subcortical deep gray matter,
      white matter, and cortical pathology is not well understood in MS. The aim of
      this study was to use DTI to investigate the subcortical deep gray matter
      alterations and their relationship with lesion burden, white matter, and cortical
      atrophy in patients with MS and healthy control patients. MATERIALS AND METHODS:
      A total of 210 patients with relapsing-remitting MS, 75 patients with progressive
      MS, and 110 healthy control patients were included in the study. DTI metrics in
      whole brain, normal-appearing white matter, normal-appearing gray matter, and
      subcortical deep gray matter structures were compared. The association between
      DTI metrics of the subcortical deep gray matter structures with lesion burden,
      normalized white matter volume, and normalized cortical volume was investigated.
      RESULTS: DTI measures were significantly different in whole brain, normal
      appearing white matter, and normal-appearing gray matter among the groups (P <
      .01). Significant differences in DTI diffusivity of total subcortical deep gray
      matter, caudate, thalamus, and hippocampus (P < .001) were found. DTI diffusivity
      of total subcortical deep gray matter was significantly associated with
      normalized white matter volume (P < .001) and normalized cortical volume (P =
      .033) in healthy control patients. In both relapsing and progressive MS groups,
      the DTI subcortical deep gray matter measures were associated with the lesion
      burden and with normalized white matter volume (P < .001), but not with
      normalized cortical volume. CONCLUSIONS: These findings suggest that subcortical
      deep gray matter abnormalities are associated with white matter lesion burden and
      atrophy, whereas cortical atrophy is not associated with microstructural
      alterations of subcortical deep gray matter structures in patients with MS.

PMID- 24335549
TI  - I. Adult cardiopulmonary resuscitation: 'who' rather than 'how'.

PMID- 24335550
TI  - Determination of cardiac output by ultrasound dilution technique in infants and
      children: a validation study against direct Fick principle.
AB  - BACKGROUND: In critically ill children, monitoring of cardiac output (CO) is
      essential to guide haemodynamic management and facilitate cardiovascular therapy.
      The ultrasound dilution technique (UDT), a novel minimally invasive indicator
      method, was recently introduced to determine CO. We validated UDT against the
      'gold standard' reference technique, the direct Fick principle, in infants and
      children. METHODS: Twenty-six children (median age: 6 yr 2 months; median weight:
      19.2 kg) underwent diagnostic heart catheterization. In each child, CO was
      determined by the Fick principle using direct measurement of oxygen consumption
      and invasive oximetry. Consecutively, haemodynamically stable conditions
      provided; three independent measurements of CO were conducted with UDT. CO values
      were compared using bias and limits of agreement calculated using the Bland
      Altman approach and linear regression analysis for the complete study group and
      for a subgroup with body weight <20 kg (n=14). RESULTS: The mean (standard
      deviation) CO values were 3.76 (1.73) litre min(-1) (range 1.38-6.97) for the
      direct Fick principle and 3.49 (1.72) litre min(-1) (range 1.31-7.00) for UDT. An
      excellent correlation (r=0.96) was found between both methods (P<0.0001). The
      Bland-Altman analysis demonstrated good clinical agreement with a mean bias of
      0.26 litre min(-1), limits of agreement of -0.66 and 1.19 litre min(-1), and
      percentage error of 25.9%. Comparable results were obtained for patients <20 kg
      (mean bias=0.19 litre min(-1), percentage error=25.5%). CONCLUSIONS: CO
      measurements by UDT agree favourably with Fick-derived CO data and both
      techniques were found to be equivalent and interchangeable. UDT represents a
      valid and applicable method for repetitive CO determinations in infants and
      children.

PMID- 24335551
TI  - Limits of agreement between measures obtained from standard laboratory and the
      point-of-care device Hemochron Signature Elite(R) during acute haemorrhage.
AB  - BACKGROUND: Rapid diagnosis of coagulopathy in the bleeding patient using point
      of-care (POC) devices would be ideal. The Hemochron Signature Elite((r))
      (HC((r))) is a POC device that determines international normalized ratio (INR)
      and activated partial thromboplastin time (aPTT). The aim of the study was to
      evaluate the agreement for INR and aPTT between the HC((r)) and standard
      laboratory values in acute haemorrhage. METHODS: This was a single-centre
      observational prospective study including patients with acute haemorrhage.
      Laboratory INR and aPTT were compared with simultaneous measurements performed
      with the HC((r)). The diagnostic performance of HC((r)) was determined; bias and
      limits of agreement were calculated according to the method of Bland and Altman.
      RESULTS: Seventy-two pairs of measurements from 39 patients were analysed. The
      bias between the INR-HC((r)) and aPTT-HC((r)) measurements and the central
      laboratory were 0.02 and -1.13, respectively. The Spearman's correlation
      coefficients for the INR-HC((r))/INR-lab and the aPTT-HC((r))/aPTT-lab were 0.68
      and -0.29, respectively. Twenty-seven per cent of INR-HC((r)) values and 89% of
      the aPTT-HC((r)) values exceeded the predefined limits of agreement. The INR
      HC((r)) measurement identified patients with a central laboratory INR >1.5 with a
      sensitivity, specificity, and positive and negative predictive values of 83%,
      70%, 76%, and 77%, respectively. CONCLUSIONS: The results showed a lack of
      agreement between the INR-HC((r)) and the aPTT-HC((r)) measurements and the
      standard laboratory in the context of acute haemorrhage. The INR-HC((r)) showed
      moderate performance as a decision-making tool to detect coagulopathy in the
      context of acute haemorrhage.

PMID- 24335552
TI  - Ketamine should be upgraded from class C to class B drug, committee says.

PMID- 24335553
TI  - Long-term silencing of autoimmune diabetes and improved life expectancy by a
      soluble pHLA-DR4 chimera in a newly-humanized NOD/DR4/B7 mouse.
AB  - Several human MHC class II (HLA) molecules are strongly associated with high
      incidence of autoimmune diseases including type 1 diabetes (T1D). The HLA
      humanized mice may thus represent valuable tools to test HLA-based vaccines and
      therapeutics for human autoimmune diseases. Herein, we have tested the
      therapeutic potential of a soluble HLA-DR4-GAD65 271-280 (hu DEF-GAD65) chimera
      of human use in a newly-generated NOD/DR4/B7 double transgenic (dTg) mouse that
      develops spontaneously an accelerated T1D regardless the gender. The NOD/DR4/B7
      dTg mice generated by a two-step crossing protocol express the HLA-DR*0401
      molecules on 20% of antigen presenting cells, the human B7 molecules in pancreas,
      and HLA-DR4/GAD65-specific T-cells in the blood. Some 75% of pre-diabetic
      NOD/DR4/B7 dTg mice treated with hu DEF-GAD65 chimera remained euglycemic and
      showed a stabilized pancreatic insulitis 6 months after treatment. The 25% non
      responders developing hyperglycemia survived 3-4 months longer than their
      untreated littermates. T1D prevention by this reagent occurred by a Th2/TR-1
      polarization in the pancreas. This study strongly suggests that the use of
      soluble pHLA reagents to suppress/stabilize the T1D progression and to extend the
      life expectancy in the absence of side effects is an efficient and safe
      therapeutic approach. 

PMID- 24335554
TI  - Blockade of SDF-1 after irradiation inhibits tumor recurrences of autochthonous
      brain tumors in rats.
AB  - BACKGROUND: Tumor irradiation blocks local angiogenesis, forcing any recurrent
      tumor to form new vessels from circulating cells. We have previously demonstrated
      that the post-irradiation recurrence of human glioblastomas in the brains of nude
      mice can be delayed or prevented by inhibiting circulating blood vessel-forming
      cells by blocking the interaction of CXCR4 with its ligand stromal cell-derived
      factor (SDF)-1 (CXCL12). In the present study we test this strategy by directly
      neutralizing SDF-1 in a clinically relevant model using autochthonous brain
      tumors in immune competent hosts. METHODS: We used NOX-A12, an l-enantiomeric RNA
      oligonucleotide that binds and inhibits SDF-1 with high affinity. We tested the
      effect of this inhibitor on the response to irradiation of brain tumors in rat
      induced by n-ethyl-N-nitrosourea. RESULTS: Rats treated in utero with N-ethyl-N
      nitrosourea began to die of brain tumors from approximately 120 days of age. We
      delivered a single dose of whole brain irradiation (20 Gy) on day 115 of age,
      began treatment with NOX-A12 immediately following irradiation, and continued
      with either 5 or 20 mg/kg for 4 or 8 weeks, doses and times equivalent to well
      tolerated human exposures. We found a marked prolongation of rat life span that
      was dependent on both drug dose and duration of treatment. In addition we treated
      tumors only when they were visible by MRI and demonstrated complete regression of
      the tumors that was not achieved by irradiation alone or with the addition of
      temozolomide. CONCLUSIONS: Inhibition of SDF-1 following tumor irradiation is a
      powerful way of improving tumor response of glioblastoma multiforme.

PMID- 24335556
TI  - A tribute to a brilliant mind: Jerry Vloka, MD, PhD.

PMID- 24335555
TI  - Microbial and metabolic interactions between the gastrointestinal tract and
      Clostridium difficile infection.
AB  - Antibiotics disturb the gastrointestinal tract microbiota and in turn reduce
      colonization resistance against Clostridium difficile. The mechanism for this
      loss of colonization resistance is still unknown but likely reflects structural
      (microbial) and functional (metabolic) changes to the gastrointestinal tract.
      Members of the gut microbial community shape intestinal metabolism that provides
      nutrients and ultimately supports host immunity. This review will discuss how
      antibiotics alter the structure of the gut microbiota and how this impacts
      bacterial metabolism in the gut. It will also explore the chemical requirements
      for C. difficile germination, growth, toxin production and sporulation. Many of
      the metabolites that influence C. difficile physiology are products of gut
      microbial metabolism including bile acids, carbohydrates and amino acids. To
      restore colonization resistance against C. difficile after antibiotics a targeted
      approach restoring both the structure and function of the gastrointestinal tract
      is needed. 

PMID- 24335557
TI  - Vision-based flight control in the hawkmoth Hyles lineata.
AB  - Vision is a key sensory modality for flying insects, playing an important role in
      guidance, navigation and control. Here, we use a virtual-reality flight simulator
      to measure the optomotor responses of the hawkmoth Hyles lineata, and use a
      published linear-time invariant model of the flight dynamics to interpret the
      function of the measured responses in flight stabilization and control. We
      recorded the forces and moments produced during oscillation of the visual field
      in roll, pitch and yaw, varying the temporal frequency, amplitude or spatial
      frequency of the stimulus. The moths' responses were strongly dependent upon
      contrast frequency, as expected if the optomotor system uses correlation-type
      motion detectors to sense self-motion. The flight dynamics model predicts that
      roll angle feedback is needed to stabilize the lateral dynamics, and that a
      combination of pitch angle and pitch rate feedback is most effective in
      stabilizing the longitudinal dynamics. The moths' responses to roll and pitch
      stimuli coincided qualitatively with these functional predictions. The moths
      produced coupled roll and yaw moments in response to yaw stimuli, which could
      help to reduce the energetic cost of correcting heading. Our results emphasize
      the close relationship between physics and physiology in the stabilization of
      insect flight. 

PMID- 24335558
TI  - Calcium waves initiating from the anomalous subdiffusive calcium sparks.
AB  - The objective of the study is to investigate the propagation of Ca(2+) waves in
      full-width cardiac myocytes and carry out sensitivity analysis to study the
      effects of various physiological parameters on global Ca(2+) waves. Based on the
      anomalous subdiffusion of Ca(2+) sparks, a mathematical model was proposed to
      characterize the Ca(2+) waves. The computed results were in agreement with the
      experimental measurements using confocal microscopy. This model includes
      variables of current through the Ca(2+) release unit (CRU; ICRU), duration of
      current flow through CRU (Topen), Ca(2+) sensitivity parameter (K), the
      longitudinal and transverse spatial separation of CRUs (lx and ly, where x
      denotes longitudinal direction (x-axis) and y denotes transverse direction (y
      axis)) and Ca(2+) diffusion coefficients (Dx, Dy). The spatio-temporal mechanism
      of the anomalous Ca(2+) sparks led to results that were different from those
      based on Fick's law. The major findings were reported as: ICRU affected the
      dynamic properties of Ca(2+) waves more significantly than Topen; the effect of K
      on the properties of Ca(2+) waves was negligible; ly affected the amplitude
      significantly, but lx affected the longitudinal velocity significantly; in turn,
      the limitation and significance of the study are discussed.

PMID- 24335559
TI  - Global warming alters sound transmission: differential impact on the prey
      detection ability of echolocating bats.
AB  - Climate change impacts the biogeography and phenology of plants and animals, yet
      the underlying mechanisms are little known. Here, we present a functional link
      between rising temperature and the prey detection ability of echolocating bats.
      The maximum distance for echo-based prey detection is physically determined by
      sound attenuation. Attenuation is more pronounced for high-frequency sound, such
      as echolocation, and is a nonlinear function of both call frequency and ambient
      temperature. Hence, the prey detection ability, and thus possibly the foraging
      efficiency, of echolocating bats and susceptible to rising temperatures through
      climate change. Using present-day climate data and projected temperature rises,
      we modelled this effect for the entire range of bat call frequencies and climate
      zones around the globe. We show that depending on call frequency, the prey
      detection volume of bats will either decrease or increase: species calling above
      a crossover frequency will lose and species emitting lower frequencies will gain
      prey detection volume, with crossover frequency and magnitude depending on the
      local climatic conditions. Within local species assemblages, this may cause a
      change in community composition. Global warming can thus directly affect the prey
      detection ability of individual bats and indirectly their interspecific
      interactions with competitors and prey. 

PMID- 24335560
TI  - Regulatory principles and experimental approaches to the circadian control of
      starch turnover.
AB  - In many plants, starch is synthesized during the day and degraded during the
      night to avoid carbohydrate starvation in darkness. The circadian clock
      participates in a dynamic adjustment of starch turnover to changing environmental
      condition through unknown mechanisms. We used mathematical modelling to explore
      the possible scenarios for the control of starch turnover by the molecular
      components of the plant circadian clock. Several classes of plausible models were
      capable of describing the starch dynamics observed in a range of clock mutant
      plants and light conditions, including discriminating circadian protocols. Three
      example models of these classes are studied in detail, differing in several
      important ways. First, the clock components directly responsible for regulating
      starch degradation are different in each model. Second, the intermediate species
      in the pathway may play either an activating or inhibiting role on starch
      degradation. Third, the system may include a light-dependent interaction between
      the clock and downstream processes. Finally, the clock may be involved in the
      regulation of starch synthesis. We discuss the differences among the models'
      predictions for diel starch profiles and the properties of the circadian
      regulators. These suggest additional experiments to elucidate the pathway
      structure, avoid confounding results and identify the molecular components
      involved. 

PMID- 24335561
TI  - Three-dimensional vortex wake structure of flapping wings in hovering flight.
AB  - Flapping wings continuously create and send vortices into their wake, while
      imparting downward momentum into the surrounding fluid. However, experimental
      studies concerning the details of the three-dimensional vorticity distribution
      and evolution in the far wake are limited. In this study, the three-dimensional
      vortex wake structure in both the near and far field of a dynamically scaled
      flapping wing was investigated experimentally, using volumetric three-component
      velocimetry. A single wing, with shape and kinematics similar to those of a
      fruitfly, was examined. The overall result of the wing action is to create an
      integrated vortex structure consisting of a tip vortex (TV), trailing-edge shear
      layer (TESL) and leading-edge vortex. The TESL rolls up into a root vortex (RV)
      as it is shed from the wing, and together with the TV, contracts radially and
      stretches tangentially in the downstream wake. The downwash is distributed in an
      arc-shaped region enclosed by the stretched tangential vorticity of the TVs and
      the RVs. A closed vortex ring structure is not observed in the current study
      owing to the lack of well-established starting and stopping vortex structures
      that smoothly connect the TV and RV. An evaluation of the vorticity transport
      equation shows that both the TV and the RV undergo vortex stretching while
      convecting downwards: a three-dimensional phenomenon in rotating flows. It also
      confirms that convection and secondary tilting and stretching effects dominate
      the evolution of vorticity. 

PMID- 24335562
TI  - An automatic service for the personalization of ventricular cardiac meshes.
AB  - Computational cardiac physiology has great potential to improve the management of
      cardiovascular diseases. One of the main bottlenecks in this field is the
      customization of the computational model to the anatomical and physiological
      status of the patient. We present a fully automatic service for the geometrical
      personalization of cardiac ventricular meshes with high-order interpolation from
      segmented images. The method is versatile (able to work with different species
      and disease conditions) and robust (fully automatic results fulfilling accuracy
      and quality requirements in 87% of 255 cases). Results also illustrate the
      capability to minimize the impact of segmentation errors, to overcome the sparse
      resolution of dynamic studies and to remove the sometimes unnecessary anatomical
      detail of papillary and trabecular structures. The smooth meshes produced can be
      used to simulate cardiac function, and in particular mechanics, or can be used as
      diagnostic descriptors of anatomical shape by cardiologists. This fully automatic
      service is deployed in a cloud infrastructure, and has been made available and
      accessible to the scientific community. 

PMID- 24335563
TI  - Collective thermoregulation in bee clusters.
AB  - Swarming is an essential part of honeybee behaviour, wherein thousands of bees
      cling onto each other to form a dense cluster that may be exposed to the
      environment for several days. This cluster has the ability to maintain its core
      temperature actively without a central controller. We suggest that the swarm
      cluster is akin to an active porous structure whose functional requirement is to
      adjust to outside conditions by varying its porosity to control its core
      temperature. Using a continuum model that takes the form of a set of advection
      diffusion equations for heat transfer in a mobile porous medium, we show that the
      equalization of an effective 'behavioural pressure', which propagates information
      about the ambient temperature through variations in density, leads to effective
      thermoregulation. Our model extends and generalizes previous models by focusing
      the question of mechanism on the form and role of the behavioural pressure, and
      allows us to explain the vertical asymmetry of the cluster (as a consequence of
      buoyancy-driven flows), the ability of the cluster to overpack at low ambient
      temperatures without breaking up at high ambient temperatures, and the relative
      insensitivity to large variations in the ambient temperature. Our theory also
      makes testable hypotheses for the response of the cluster to external temperature
      inhomogeneities and suggests strategies for biomimetic thermoregulation. 

PMID- 24335564
TI  - Potential for biomarkers of chronic kidney disease-mineral bone disorder to
      improve patient care.
AB  - Chronic kidney disease (CKD) is a growing public health problem. Cardiovascular
      disease is common in CKD, but standard risk assessment tools perform poorly in
      this population. Equally, despite CKD being associated with an increased risk for
      death and dialysis, standard biochemical measurements have limited prognostic
      value. Novel serum biomarkers may aid risk assessment; however, studies have
      shown varying clinical utility in relation to progression of CKD, incident
      cardiovascular disease and death. This inconsistency may relate to limitations in
      our understanding of the biological actions and interactions of these biomarkers.
      This review discusses a range of biomarkers in relation to these clinical
      endpoints in CKD-mineral bone disorder. We consider where biomarkers may enhance
      risk stratification and improve clinical management, but also highlight where
      they fall short of achieving this objective.

PMID- 24335565
TI  - Implication of lymph node metastasis detected on 18F-FDG PET/CT for surgical
      planning in patients with peripheral intrahepatic cholangiocarcinoma.
AB  - OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is the second most common
      primary hepatic malignancy after hepatocellular carcinoma. ICC can be divided
      into 2 types according to their location: peripheral and hilar types. Intense F
      FDG uptake on PET was reported in peripheral ICC. However, the usefulness of
      PET/CT in detecting tumors and predicting prognosis in peripheral ICC has not
      been fully evaluated. In this study, we evaluated the clinical role of F-FDG
      PET/CT to predict the recurrence after the curative resection in patients with
      surgically indicated peripheral ICC. METHODS: Eighteen patients with ICC
      underwent preoperative CT and F-FDG PET/CT scans. SUVmax of tumor, tumor to
      normal liver SUV ratio (TNR), lymph node status evaluated by F-FDG PET/CT, tumor
      and lymph node size measured by CT, vascular invasion confirmed by pathology, and
      satellite nodules found on CT were compared between 1-year recurrence group and
      recurrence-free group by chi-square test. RESULTS: Of total 23 measurable lymph
      nodes, 4 nodes were positive and other 19 nodes were negative or equivocal on CT.
      Among those 23 nodes, 9 nodes were positive and other 14 nodes were negative on F
      FDG PET/CT. The sensitivity and specificity of CT were 20.0% and 86.4%, and those
      of F-FDG PET/CT were 80.0% and 92.3%. In the comparison between 1-year recurrent
      and nonrecurrent groups, lymph node metastasis detected on F-FDG PET/CT had
      statistically positive correlation with the 1-year recurrence after surgical
      resection (P = 0.02). Other factors showed no statistically significant
      difference between the groups. CONCLUSION: We found that lymph node metastasis
      detected on F-FDG PET/CT correlated positively with 1-year recurrence after
      surgical resection in patients with peripheral ICC.

PMID- 24335566
TI  - A pilot study on EGFR-targeted molecular imaging of PET/CT With 11C-PD153035 in
      human gliomas.
AB  - 11C-PD153035, a potent and specific ATP-competitive tyrosine kinase inhibitor
      (TKI) of the EGF receptor, has been developed for PET imaging of epidermal growth
      factor receptor (EGFR) in lung cancer. The objective of the present study was to
      investigate the relationship of the accumulation of 11C-PD153035 and the EGFR
      expression level in human gliomas and to explore whether 11C-PD153035 can be used
      in the molecular imaging of glioma with EGFR overexpression. Eleven patients with
      histopathologically proven gliomas underwent 11C-PD153035 PET/CT examination
      before surgery. Combining MRI with the 11C-PD153035 PET/CT image, 2 specimens
      from different C-PD153035 uptake regions of each tumor and adjacent normal brain
      tissue were selected as the biopsy targets through the stereotactic technique.
      The radioactivity concentrations were analyzed as the mathematical maximum
      standardized uptake value (SUVmax) in region of interest (ROI). The EGFR
      expression in the biopsied tissues was analyzed by immunohistochemical staining
      (IHC) and western blotting. The SUVmax/WM (11C-PD153035 uptake in the white
      matter of the contralateral normal hemisphere) ratio was used to indicate the
      EGFR expression level in the ROI in PET/CT, and it was correlated with the EGFR
      expression detected by IHC and western blot analysis. The results demonstrated
      that 6 of the 8 patients with glioblastoma (GBM) were obviously visualized by 11C
      PD153035 PET/CT, whereas 2 patients with GBM, 1 with anaplastic astrocytoma, and
      2 with oligodendroglioma did not show significant 11C-PD153035 uptake. There were
      positive correlations between the SUVmax/WM and the results of IHC (r = 0.955, P
      < 0.01) and western blotting(r = 0.889, P < 0.010). Our preliminary findings
      suggest that 11C-PD153035 PET/CT is a promising method for the EGFR-targeted
      molecular imaging of human GBM, which may be translated into the clinic to select
      the appropriate population of patients for EGFR-targeted therapy and to assess
      the early targeted therapeutic response of malignant gliomas.

PMID- 24335567
TI  - Correlations between 18F-FDG PET/CT parameters and pathological findings in
      patients with rectal cancer.
AB  - PURPOSE: This study examined the correlations between F-FDG PET/CT results and
      tumor specimen pathology in patients with rectal cancer. METHODS: Sixty-seven
      patients with rectal cancer who had received preoperative PET/CT were included in
      this study. Autosegmentation methods were used to determine the maximum PET/CT
      based tumor length (TL), tumor width (TW), and metabolic tumor volume for each
      patient. The TL and TW values were compared with the maximum pathological length
      and width of the tumor specimen. To forecast the pathological T and N stages, a
      receiver operating characteristic curve was created for each parameter to
      evaluate its predictive ability. Logistic regression analysis was used to
      identify the predictors of pathology. RESULTS: The values of 30% of maximum
      uptake for TL and 40% of maximum uptake for TW provided the best match with the
      maximum pathological tumor length and width (Pearson r = 0.72, P < 0.001; r =
      0.44, P < 0.001, respectively). Metabolic tumor volume with a fixed threshold of
      2.5 emerged as an independent factor for predicting the pathological T3 or T4
      stage (P = 0.001; odds ratio, 1.81; 95% confidence interval, 1.26-2.60).
      CONCLUSIONS: Preoperative PET/CT can be used as a supplemental tool in predicting
      pathological findings for patients with rectal cancer requiring operation.

PMID- 24335568
TI  - The impact of hepatitis C infection on ischemic heart disease via ischemic
      electrocardiogram.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a serious disease worldwide and
      it leads to several serious hepatic sequels. Some studies find possible
      correlation between HCV and ischemic heart disease in retrospective observations.
      Based on lacked community-based evidence, the study aims to assess correlation
      between ischemic heart disease and chronic HCV infection via electrocardiogram
      (ECG) because its abnormalities is strongly associating with cardiovascular
      disease mortality. METHODS: The population was from one community health
      examination in December 2010 in a southern village of Taiwan. A total of 9856
      participants were evaluated and finally 5015 eligible residents with age older
      than 40 years were included. The baseline characteristics and laboratory data in
      nonischemic ECG and ischemic ECG groups were compared, and multivariate-adjusted
      analysis was used to evaluate the risks to ischemic ECG. RESULTS: The higher
      prevalence of hypertension, metabolic syndrome and even HCV infection (25.3%
      versus 11.6%; P < 0.001) in ischemic ECG group than those in nonischemic ECG
      group. In the multivariate adjusted analysis, HCV infection would lead to a 1.759
      fold risk to ischemic ECG when compared with non-HCV subjects. CONCLUSIONS: HCV
      was strongly associated with ischemic ECG findings in this community study, and
      it could be a nonconventional risk factor for coronary artery disease.

PMID- 24335569
TI  - Inverse correlation between circulating endothelial progenitor cells with
      CD34+CD133+ and the severity of coronary atherosclerosis assessed by Syntax
      score.
AB  - BACKGROUND: The number of endothelial progenitor cells (EPCs) descends when
      atherosclerosis developed. The objective was to compare the number of
      CD34(+)CD133(+) cells with the severity of atherosclerosis assessed by Syntax
      score. METHODS: The study included 80 patients with stable angina undergoing
      coronary angiography. Patients were classified into single-vessel group, multiple
      vessel group and normal group according to angiography. The percentage of
      CD34(+)CD133(+) cells in the mononuclear cells isolated from peripheral blood of
      different groups by flow cytometric analysis was compared. The quantity of
      CD34(+)CD133(+) EPCs was log transformed to improve normality (lgEPC). Syntax
      score was used in this study to assess the extent of coronary artery disease.
      RESULTS: The level of lgEPC was lower in the single-vessel group than that in the
      normal group (-3.42 +/- 0.44 versus -3.17 +/- 0.39, P < 0.05), and the level of
      lgEPC was lower in the multiple-vessel group than that in the single vessel group
      (-3.63 +/- 0.31 versus -3.42 +/- 0.44, P < 0.05). An inverse correlation between
      lgEPC and Syntax score analyzed by linear regression. CONCLUSIONS: EPC level
      probably serves as a predictor of the development and severity of atherosclerosis
      on a cellular level. EPC, a relatively more important risk factor, perhaps
      protects against coronary artery disease.

PMID- 24335571
TI  - Extending the glucosyl ceramide cassette approach: application in the total
      synthesis of ganglioside GalNAc-GM1b.
AB  - The development of a novel cyclic glucosyl ceramide cassette acceptor for
      efficient glycolipid syntheses was investigated. p-Methoxybenzyl (PMB) groups
      were selected as protecting groups at C2 and C3 of the glucose residue with the
      aim of improving the functionality of the cassette acceptor. The choice of the
      PMB group resulted in a loss of beta-selectivity, which was corrected by using an
      appropriate tether to control the spatial arrangement and the nitrile solvent
      effect. To investigate the effect of linker structure on the beta-selectivity of
      intramolecular glycosylation, several linkers for tethering the glucose and
      ceramide moiety were designed and prepared, namely, succinyl, glutaryl,
      dimethylmalonyl, and phthaloyl esters. The succinyl ester linker was the best for
      accessing the cassette form. The newly designed glucosyl ceramide cassette
      acceptor was then applied in the total synthesis of ganglioside GalNAc-GM1b. 

PMID- 24335572
TI  - Efficient PPA-SiO2-catalyzed synthesis of beta-enaminones under solvent-free
      conditions.
AB  - An efficient method has been developed for the synthesis of beta-enaminones under
      solvent-free reaction conditions using PPA-SiO2 as catalyst. The reaction yields
      were good to excellent (up to 90%). This methodology affords high selectivity and
      good tolerance of a variety of different functional groups present on both
      aromatic and aliphatic amines. In addition, the methodology is environmentally
      benign and cost-effective due to absence of solvent and easy work-up. 

PMID- 24335573
TI  - Facile synthesis of the naturally cytotoxic triterpenoid saponin Patrinia
      glycoside B-II and its conformer.
AB  - The first chemical synthesis of the natural triterpenoid saponin Patrinia
      glycoside B-II, namely oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1->2)-[beta-D
      gluco-pyranosyl-(1->3)]-alpha-L-arabinopyranoside, has been accomplished in a
      linear 11-step sequence 11 with 9.4% overall yield. The abnormal 1C4 conformation
      of the arabinose residue was found to occur via conformational fluctuation during
      preparation of the intermediates. Molecular mechanism and quantum chemistry
      calculations showed that Patrinia-glycoside B-II and its conformer 1 cannot
      interconvert under normal conditions. Preliminary structure-activity
      relationships studies indicated that the 4C1 chair conformation of the arabinose
      residue in the unique alpha-L-rhamnopyranosyl-(1->2)-alpha-L-arabinopyranosyl
      disaccharide moiety is one of the chief positive factors responsible for its
      cytotoxic activity against tumors. 

PMID- 24335570
TI  - Immunotherapeutic approaches to treat multiple myeloma.
AB  - Cellular immunotherapy can be an effective adjuvant treatment for multiple
      myeloma (MM), as demonstrated by induction of durable remissions after allogeneic
      stem cell transplantation. However, anti-myeloma immunity is often hampered by
      suppressive mechanisms in the tumor micro-environment resulting in relapse or
      disease progression. To overcome this immunosuppression, new cellular
      immunotherapies have been developed, based on the important effector cells in
      anti-myeloma immunity, namely T cells and natural killer cells. These effectors
      can be modulated to improve their functionality, activated by dendritic cell
      vaccines, or combined with immune stimulating antibodies or immunomodulatory
      drugs to enhance their efficacy. In this review, we discuss promising pre
      clinical and clinical data in the field of cellular immunotherapy in MM. In
      addition, we address the potential of combining these strategies with other
      therapies to maximize clinical effects without increasing toxicity. The reviewed
      therapies might pave the way to effective personalized treatments for MM
      patients. 

PMID- 24335574
TI  - Repetitive two-step method for o,o,p- and o,p-oligophenylene synthesis through Pd
      catalyzed cross-coupling of hydroxyterphenylboronic acid.
AB  - A repetitive two-step method involving the Pd-catalyzed Suzuki-Miyaura coupling
      of hydroxyterphenylboronic acid and the subsequent nonaflation of the hydroxy
      group has been developed for the synthesis of oligophenylenes. This method
      readily afforded o,o,p- and o,p-oligophenylenes with defined chain lengths. X-ray
      crystallography was employed to obtain the structure of the o,p-oligophenylene 9
      mer. 

PMID- 24335575
TI  - Chemical and biological properties of quinochalcone C-glycosides from the florets
      of Carthamus tinctorius.
AB  - Quinochalcone C-glycosides are regarded as characteristic components that have
      only been isolated from the florets of Carthamus tinctorius. Recently,
      quinochalcone C-glycosides were found to have multiple pharmacological
      activities, which has attracted the attention of many researchers to explore
      these compounds. This review aims to summarize quinochalcone C-glycosides'
      physicochemical properties, chromatographic behavior, spectroscopic
      characteristics, as well as their biological activities, which will be helpful
      for further study and development of quinochalcone C-glycosides. 

PMID- 24335576
TI  - Synthesis and structure-activity relationships of novel ecdysteroid dioxolanes as
      MDR modulators in cancer.
AB  - Ecdysteroids, molting hormones of insects, can exert several mild, non-hormonal
      bioactivities in mammals, including humans. In a previous study, we have found a
      significant effect of certain derivatives on the ABCB1 transporter mediated multi
      drug resistance of a transfected murine leukemia cell line. In this paper, we
      present a structure-activity relationship study focused on the apolar dioxolane
      derivatives of 20-hydroxyecdysone. Semi-synthesis and bioactivity of a total of
      32 ecdysteroids, including 20 new compounds, is presented, supplemented with
      their complete 1H- and 13C-NMR signal assignment. 

PMID- 24335577
TI  - Antimalarial activity of 4-metoxychalcones: docking studies as
      falcipain/plasmepsin inhibitors, ADMET and lipophilic efficiency analysis to
      identify a putative oral lead candidate.
AB  - Herein, we report the antimalarial activity of nine 4-methoxychalcone derivatives
      1a-i and an initial analysis of their ADMET properties. All compounds showed
      potent activity against the P. falciparum chloroquine-resistant clone W2, with
      IC50 values ranging from 1.96 uM to 10.99 uM, with moderate or low cytotoxicity
      against the HeLa cell line. The compound 1a (IC50 = 2.06 uM) had the best
      selectivity index (9.0). All the sulfonamide 4-metychalcone derivatives
      synthesized had cLogP values between 2 and 5 (mean value 3.79) and molecular
      weights (MWs) below 500. The substitution of the pyrrolidine group in 1i by a
      morpholine group in 1a reduced the cLogP value from 3.05 in compound 1i to 2.34
      in compound 1a. Indeed, compound 1a had the highest LipE value. The binding free
      energy of compound 1a showed it to be the most optimal chalcone derivative for
      plasmepsin-2 (-7.3 Kcal/mol). The physicochemical properties and LipE analysis of
      the dataset allowed us to establish that compound 1a is the highest quality
      compound of the series and a potential oral lead candidate. 

PMID- 24335578
TI  - Structure activity relationships of N-linked and diglycosylated glucosamine-based
      antitumor glycerolipids.
AB  - 1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-beta-D-glucopyranosyl)-sn
      glycerol (1) was previously reported to show potent in vitro antitumor activity
      on a range of cancer cell lines derived from breast, pancreas and prostate
      cancer. This compound was not toxic to mice and was inactive against breast tumor
      xenografts in mice. This inactivity was attributed to hydrolysis of the
      glycosidic linkage by glycosidases. Here three N-linked (glycosylamide) analogs 2
      4, one triazole-linked analog 5 of 1 as well as two diglycosylated analogs 6 and
      7 with different stereochemistry at the C2-position of the glycerol moiety were
      synthesized and their antitumor activity against breast (JIMT-1, BT-474, MDA-MB
      231), pancreas (MiaPaCa2) and prostrate (DU145, PC3) cancer cell lines was
      determined. The diglycosylated analogs 1-O-hexadecyl-2(R)-, 3-O-di-(2'-amino-2'
      deoxy-beta-D-glucopyranosyl)-sn-glycerol (7) and the 1:1 diastereomeric mixture
      of 1-O-hexadecyl-2(R/S), 3-O-di-(2'-amino-2'-deoxy-beta-D-glucopyranosyl)-sn
      glycerol (6) showed the most potent cytotoxic activity at CC50 values of 17.5 uM
      against PC3 cell lines. The replacement of the O-glycosidic linkage by a
      glycosylamide or a glycosyltriazole linkage showed little or no activity at
      highest concentration tested (30 uM), whereas the replacement of the glycerol
      moiety by triazole resulted in CC50 values in the range of 20 to 30 uM. In
      conclusion, the replacement of the O-glycosidic linkage by an N-glycosidic
      linkage or triazole-linkage resulted in about a two to three fold loss in
      activity, whereas the replacement of the methoxy group on the glycerol backbone
      by a second glucosamine moiety did not improve the activity. The stereochemistry
      at the C2-position of the glycero backbone has minimal effect on the anticancer
      activities of these diglycosylated analogs. 

PMID- 24335579
TI  - Visualization of developmental dysplasia of the hip in infants by using three
      dimensional magnetic resonance imaging.
AB  - Developmental dysplasia of the hip (DDH) includes various abnormalities such as
      instability, subluxation, and dislocation. In selecting the appropriate treatment
      method, it is important to distinguish these abnormalities from each other. We
      developed a novel approach for diagnosing DDH using three-dimensional MRI, which
      are used to visualize the spatial relation between the dislocated femoral head
      and the acetabulum and to clarify the changes during hip joint movement. The
      three-dimensional MRI are useful for confirming the diagnosis of DDH and for
      evaluating the reducibility of the affected hip. 

PMID- 24335580
TI  - Pharmacokinetics of a new fentanyl tape with a novel delivery system of
      transdermal matrix patches in patients with cancer pain.
AB  - OBJECTIVES: A novel delivery system for transdermal matrix patches of fentanyl
      has been developed. The new fentanyl tape consists of a backing layer, a drug
      containing layer and a release liner that is originally made of rubber adhesive.
      This open-label prospective study investigated the pharmacokinetics and safety of
      the fentanyl tape in patients with cancer pain. METHODS: The tape was applied to
      the patient's chest for 72 h, and serum samples were collected from 0 to 72 h.
      Fentanyl concentrations were determined using liquid chromatography with mass
      spectrometry. Pharmacokinetic parameters were calculated, and adverse events were
      evaluated according to the Common Terminology Criteria for Adverse Events
      (version 3.0). RESULTS: Since 1 patient treated with 2.1 mg fentanyl was found to
      represent unique pharmacokinetic parameters by Shapiro-Wilk test, only 15 of the
      16 study patients were investigated. Maximum serum concentrations (Cmax) and area
      under the curve (AUC)0-72 at 2.1 and 4.2 mg were 0.26 and 0.35 ng/ml, and 11.58
      and 15.95 ng.h/ml, respectively. The Cmax and AUC0-72 tended to increase with
      dosage from 2.1 to 4.2 mg. There were no grade 3 toxicities, and only grade 1 ALT
      and AST elevations were observed. CONCLUSION: The novel delivery system of
      fentanyl may be a very promising approach to manage cancer pain clinically.

PMID- 24335581
TI  - Standardized deceased donor kidney donation rates in the UK reveal marked
      regional variation and highlight the potential for increasing kidney donation: a
      prospective cohort study?.
AB  - BACKGROUND: The UK has implemented a national strategy for organ donation that
      includes a centrally coordinated network of specialist nurses in organ donation
      embedded in all intensive care units and a national organ retrieval service for
      deceased organ donors. We aimed to determine whether despite the national
      approach to donation there is significant regional variation in deceased donor
      kidney donation rates. METHODS: The UK prospective audit of deaths in critical
      care was analysed for a cohort of patients who died in critical care between
      April 2010 and December 2011. Multivariate logistic regression was used to
      identify the factors associated with kidney donation. The logistic regression
      model was then used to produce risk-adjusted funnel plots describing the regional
      variation in donation rates. RESULTS: Of the 27 482 patients who died in a
      critical care setting, 1528 (5.5%) became kidney donors. Factors found to
      influence donation rates significantly were: type of critical care [e.g.
      neurointensive vs general intensive care: OR 1.53, 95% confidence interval (CI)
      1.34-1.75, P<0.0001], patient ethnicity (e.g. 'Asian' vs 'white': OR 0.17, 95% CI
      0.11-0.26, P<0.0001), age (e.g. age >69 vs age 18-39 yr: OR 0.2, 0.15-0.25,
      P<0.0001), and cause of death [e.g. 'other' (excluding 'stroke' and 'trauma') vs
      'trauma': OR 0.04, 95% CI 0.03-0.05, P<0.0001]. Despite correction for these
      variables, kidney donation rates for the 20 UK kidney donor regions showed marked
      variation. The overall standardized donation rate ranged from 3.2 to 7.5%. Four
      regions had donation rates of >2 standard deviations (sd) from the mean (two
      below and two above). Regional variation was most marked for donation after
      circulatory death (DCD) kidney donors with 9 of the 20 regions demonstrating
      donation rates of >2 sd from the mean (5 below and 4 above). CONCLUSIONS: The
      marked regional variation in kidney donation rates observed in this cohort after
      adjustment for factors strongly associated with donation rates suggests that
      there is considerable scope for further increasing kidney donation rates in the
      UK, particularly DCD.

PMID- 24335583
TI  - The Francis Inquiry: from diagnosis to treatment.

PMID- 24335582
TI  - Cognitive performance before and during hemodialysis: a randomized cross-over
      trial.
AB  - BACKGROUND AND AIMS: Hemodialysis (HD) patients are educated and counseled during
      the HD procedure. There are few studies assessing whether cognitive performance
      varies with dialysis. METHODS: Using a randomized cross-over design, 40 patients
      were assigned to one of two sequences: testing 1 h before dialysis followed 1
      month later by testing during the first hour of dialysis (n = 21) versus testing
      during the first hour of dialysis followed 1 month later by 1 h before dialysis
      (n = 19). Cognitive tests were administered at each testing period. Mixed
      regression models evaluated for a dialysis effect (difference between test
      performance before vs. during dialysis) while adjusting for potential learning
      (difference between first and second tests). RESULTS: In models accounting for
      period of testing, there was no difference in test performance between 1 h before
      versus during the first hour of HD for all administered cognitive tests (p >
      0.05). A learning effect was detected between first and second test
      administration in two tests, specifically, the Word List Learning and the Digit
      Symbol Substitution Test. CONCLUSIONS: We found no difference in cognitive
      performance depending on the time of testing, suggesting that cognitive tests
      performed during the first hour of dialysis are a valid assessment of cognitive
      performance.

PMID- 24335584
TI  - Ethics teaching on 'Beginning of Life' issues in UK medical schools.
AB  - Medical ethics forms an essential component of an undergraduate medical
      programme. In the UK the Institute of Medical Ethics has released a consensus
      statement detailing its recommendations for a minimum curriculum for ethics. One
      important issue it highlights for inclusion is 'Beginning of Life', which
      includes a wide range of themes. This paper presents an evaluation of the current
      teaching and assessment of these important issues in UK medical schools,
      complemented by a specific analysis of students' reaction to the teaching they
      received at the University of Edinburgh as part of their Obstetrics and
      Gynaecology rotation. Schools which responded to the survey reported a wide range
      of teaching and assessment methods. While there was a good overall coverage of
      topics, only one of them was covered by every institution and the
      religious/cultural elements of those topics were often neglected. The medical
      schools viewed better clinical integration of ethics teaching as the best route
      to improvement, but the students reported a desire for more ethics teaching in
      the form of specific tutorials, lectures or discussions. It is likely that a
      combination of these approaches will lead to significant improvements in the
      delivery of ethics teaching in this area and in others. 

PMID- 24335585
TI  - The ethics of a smoking licence.

PMID- 24335586
TI  - Osteonecrosis of the hip in Korean patients with systemic lupus erythematosus:
      risk factors and clinical outcome.
AB  - OBJECTIVE: The objective of this paper is to identify the risk factors for
      development of symptomatic osteonecrosis (ON) and predictors of total hip
      replacement (THR) among systemic lupus erythematosus (SLE) patients in Korea.
      METHODS: The medical records of 1051 patients with SLE were reviewed, and 73
      patients with symptomatic ON were identified. Among them, 64 patients were
      eligible for the analysis. Sixty-four age- and sex-matched SLE patients without
      apparent ON were included as disease controls. The risk factors for development
      of symptomatic ON were identified by logistic regression analyses. The predictors
      of THR were determined by Cox proportional hazards regression analyses. RESULTS:
      Among 64 patients with ON, 59 had ON of the hip and 36 underwent THR. Independent
      risk factors for development of symptomatic ON included Cushingoid body habitus
      (OR 21.792 (95% confidence interval (CI) 2.594-183.083)), use of cyclophosphamide
      (OR 2.779 (95% CI 1.106-6.981)) and azathioprine (OR 2.662 (95% CI 1.143-6.200)).
      In the Cox proportional hazards model, only advanced radiological stage of ON
      (Association for Research on Osseous Circulation (ARCO) stage) was a
      statistically significant predictor of THR. In subgroup analysis with stage I-III
      ON, multivariate Cox regression analysis showed neuropsychiatric SLE (NPSLE) (HR
      6.295 (95% CI 2.178-18.192)) and cumulative prednisolone dose in the first six
      months after ON diagnosis > 0.9 g (HR 3.238 (95% CI 1.095-9.58)) to be
      independent predictors. CONCLUSIONS: Advanced ARCO stage at the onset of ON is an
      independent risk factor for THR in SLE patients with ON. In ARCO stage I-III ON,
      patients with NPSLE and those receiving > 0.9 g prednisolone during the first six
      months after the ON diagnosis are likely to require THR.

PMID- 24335587
TI  - Assessing decision quality in patient-centred care requires a preference
      sensitive measure.
AB  - A theory-based instrument for measuring the quality of decisions made using any
      form of decision technology, including both decision-aided and unaided clinical
      consultations is required to enable person- and patient-centred care and to
      respond positively to individual heterogeneity in the value aspects of decision
      making. Current instruments using the term 'decision quality' have adopted a
      decision- and thus condition-specific approach. We argue that patient-centred
      care requires decision quality to be regarded as both preference-sensitive across
      multiple relevant criteria and generic across all conditions and decisions.
      MyDecisionQuality is grounded in prescriptive multi criteria decision analysis
      and employs a simple expected value algorithm to calculate a score for the
      quality of a decision that combines, in the clinical case, the patient's
      individual preferences for eight quality criteria (expressed as importance
      weights) and their ratings of the decision just taken on each of these criteria
      (expressed as performance rates). It thus provides an index of decision quality
      that encompasses both these aspects. It also provides patients with help in
      prioritizing quality criteria for future decision making by calculating, for each
      criterion, the Incremental Value of Perfect Rating, that is, the increase in
      their decision quality score that would result if their performance rating on the
      criterion had been 100%, weightings unchanged. MyDecisionQuality, which is a web
      based generic and preference-sensitive instrument, can constitute a key patient
      reported measure of the quality of the decision-making process. It can provide
      the basis for future decision improvement, especially when the clinician (or
      other stakeholders) completes the equivalent instrument and the extent and nature
      of concordance and discordance can be established. Apart from its role in
      decision preparation and evaluation, it can also provide real time and relevant
      documentation for the patient's record. 

PMID- 24335588
TI  - Risk factors of subsequent operations after primary anterior cruciate ligament
      reconstruction.
AB  - BACKGROUND: The incidence of nonrevision reoperations after anterior cruciate
      ligament reconstruction (ACLR) is less commonly studied and quantified. PURPOSE:
      To describe the incidence of short-term reoperations after primary ACLR for the 4
      most common procedures and to evaluate the risk factors associated with these
      reoperations. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients
      who underwent ACLRs and were enrolled in an ACLR registry between February 2005
      and September 2011 were evaluated. First reoperations after primary ACLR
      performed for the 4 most common procedures (meniscal procedures, cartilage
      procedures, hardware removal procedures, and arthrofibrosis procedures) were the
      primary end points of the study. Patient, surgical, surgeon, and hospital risk
      factors associated with reoperations were evaluated, and Cox regression models
      were employed. Hazard ratios (HRs) and 95% confidence intervals (CIs) are
      reported. RESULTS: A total of 14,522 ACLRs were identified. The patients had a
      mean age of 29.4 +/- 11.5 years and were mostly male (63.3%) and white (48.3%).
      The mean follow-up was 1.9 +/- 1.5 years (range, 0-6.7 years), and the median
      time to reoperation was 301 days (interquartile range, 172-515 days). The
      reoperation rate per 100 person-years of follow-up was 1.1 for meniscal
      reoperations, 0.3 for cartilage reoperations, 0.4 for hardware removal
      reoperations, and 0.4 for arthrofibrosis reoperations. Meniscal repair at the
      index ACLR was a significant risk factor for subsequent meniscal procedures (HR,
      4.19; 95% CI, 3.10-5.67). Sports medicine fellowship training of the surgeon (HR,
      2.17; 95% CI, 1.01-4.62) and older patient age (<=17 vs >=26 years) (HR, 0.32;
      95% CI, 0.12-0.81) were significant risk factors for cartilage reoperations. Use
      of allografts (HR, 1.90; 95% CI, 1.10-3.30) and female sex (HR, 1.75; 95% CI,
      1.16-2.64) were risk factors for hardware removal reoperations. Female sex (HR,
      2.48; 95% CI, 1.66-3.71) and prior surgery (HR, 3.02; 95% CI, 1.39-6.53) were
      risk factors for subsequent surgery for arthrofibrosis. CONCLUSION: Overall short
      term reoperation rates after ACLR are relatively low. Risk factors for subsequent
      surgery vary depending on the type of surgery evaluated. Some of the risk factors
      observed for reoperations include previous meniscal repair, female sex,
      allografts, prior surgery, older patient age, and being operated on by a sports
      medicine fellowship-trained surgeon.

PMID- 24335590
TI  - Mathematical validation of a biological model for unlinking replication catenanes
      by recombination.

PMID- 24335589
TI  - A common solution to group 2 influenza virus neutralization.
AB  - The discovery and characterization of broadly neutralizing antibodies (bnAbs)
      against influenza viruses have raised hopes for the development of monoclonal
      antibody (mAb)-based immunotherapy and the design of universal influenza
      vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza
      A viruses has been previously characterized that binds to a highly conserved
      epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity
      against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043,
      which was derived from a different germ-line gene encoding a highly divergent
      amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10
      viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7
      viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex
      revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an
      alternative angle of approach and a distinct set of interactions. The
      identification of another antibody against the group 2 stem epitope suggests that
      this conserved site of vulnerability has great potential for design of
      therapeutics and vaccines. 

PMID- 24335591
TI  - Land use effects on ecosystem service provisioning in tropical watersheds, still
      an important unsolved problem.

PMID- 24335592
TI  - Techniques and applications of perioperative therapeutic plasma exchange.
AB  - PURPOSE OF REVIEW: Therapeutic plasma exchange (TPE) is a useful adjunct in the
      management of antibody-mediated disorders. The indications for TPE now include
      the perioperative setting. This review updates the anesthesiologist on the
      relevant clinical indications and precautions of plasma exchange. RECENT
      FINDINGS: Although still considered experimental, TPE for heparin-induced
      thrombocytopenia for urgent cardiac surgery is the most promising recent advance.
      SUMMARY: Plasmapheresis, or TPE, removes monoclonal antibodies, immune complexes
      and paraproteins. The utility of TPE in the perioperative period has recently
      become more apparent. Antibody-mediated disorders are associated with
      postoperative morbidity and mortality and are treated with TPE. Indications for
      TPE for cardiac surgery include heparin-induced thrombocytopenia, thrombotic
      thrombocytopenia purpura and antiphospholipid syndrome. Other indications for
      perioperative TPE are typically related to immunomodulation during solid-organ
      transplant. Immunomodulation, primarily with immunosuppressive medications and
      TPE, of a previously allosensitized recipient pretransplant increases the
      likelihood of a successful match. TPE is also useful in the management of
      intentional and inadvertent ABO incompatible recipients and is essential in the
      treatment of hyperacute rejection. TPE will likely be more utilized in the future
      and understanding the essentials of the procedure will facilitate the
      perioperative management of antibody-mediated disorders.

PMID- 24335593
TI  - Perceptions of employment-based discrimination among newly arrived foreign
      educated nurses.
AB  - OBJECTIVE: To determine whether foreign-educated nurses (FENs) perceived they
      were treated equitably in the U.S. workplace during the last period of high
      international recruitment from 2003 to 2007. BACKGROUND: With experts predicting
      that isolated nursing shortages could return as soon as 2015, it is important to
      examine the lessons learned during the last period of high international
      recruitment in order to anticipate and address problems that may be endemic to
      such periods. In this baseline study, we asked FENs who were recruited to work in
      the United States between 2003 and 2007 about their hourly wages; clinical and
      cultural orientation to the United States; wages, benefits, and shift or unit
      assignments; and job satisfaction. METHODS: In 2008, we administered a survey to
      FENs who were issued VisaScreen certificates by the Commission on Graduates of
      Foreign Nursing Schools International between 2003 and 2007. We measured four
      outcomes of interest (hourly wages, job satisfaction, adequacy of orientation,
      and perceived discrimination) and conducted descriptive and regression analyses
      to determine if country of education and recruitment model were correlated with
      the outcomes. RESULTS: We found that 51% of respondents reported receiving
      insufficient orientation and 40% reported at least one discriminatory practice
      with regard to wages, benefits, or shift or unit assignments. FENs educated in
      low-income countries and those recruited by staffing agencies were significantly
      more likely than other FENs to report that they receive inequitable treatment
      compared with their U.S. counterparts. CONCLUSIONS: These findings raise both
      practical and ethical concerns that should interest those striving to create
      positive health care workplace environments and to ensure staff retention. Health
      care leaders should take steps to ensure that FENs are, and perceive that they
      are, treated equitably.

PMID- 24335594
TI  - Self-management of urinary and fecal incontinence.
AB  - OVERVIEW: Widely used by patients to control symptoms of chronic conditions such
      as diabetes, asthma, and arthritis, self-management can also help patients with
      urinary or fecal incontinence. The authors discuss the principles of self
      management, the behaviors and skills self-managing patients need to acquire, and
      the nurse's role in reinforcing their use. They then describe strategies that can
      be incorporated within the framework of self-management to control urinary,
      fecal, or dual incontinence.

PMID- 24335595
TI  - Adding preoperative radiotherapy plus cetuximab to perioperative chemotherapy for
      resectable esophageal adenocarcinoma: a single-center prospective phase II trial.
AB  - BACKGROUND: Local and systemic recurrence are important sources of treatment
      failure following surgical resection of esophageal adenocarcinoma. We
      hypothesized that adding preoperative cetuximab and radiotherapy (cetux-RT) to
      perioperative chemotherapy would increase treatment efficacy with acceptable
      toxicity. METHODS: In this prospective phase II trial, patients were treated with
      three cycles of epirubicin, cisplatin, and capecitabine (ECX), followed by cetux
      RT. After surgery with curative intent, patients received three more cycles of
      ECX. Primary endpoints were efficacy, determined by histopathological complete
      response (pCR) rate, and safety, which was assessed with resectability rate.
      RESULTS: Of the 12 patients enrolled in this trial, six received at least one
      dose of cetux-RT. In five patients, cetux-RT was not started because of adverse
      events (AEs) related to preoperative chemotherapy; one patient had progressive
      disease. Addition of cetux-RT was well tolerated and did not interfere with the
      resectability rate (100%). However, the pCR rate was 0, and 50% of patients
      experienced serious adverse events (SAEs) postoperatively. CONCLUSION: With 12
      patients enrolled, the lack of initial signs of efficacy and a high incidence of
      postoperative SAEs prompted us to end this study prematurely. Perioperative ECX
      was associated with considerable toxicity, and further treatment intensification
      is problematic.

PMID- 24335599
TI  - Are the "memory wars" over? A scientist-practitioner gap in beliefs about
      repressed memory.
AB  - The "memory wars" of the 1990s refers to the controversy between some clinicians
      and memory scientists about the reliability of repressed memories. To investigate
      whether such disagreement persists, we compared various groups' beliefs about
      memory and compared their current beliefs with beliefs expressed in past studies.
      In Study 1, we found high rates of belief in repressed memory among
      undergraduates. We also found that greater critical-thinking ability was
      associated with more skepticism about repressed memories. In Study 2, we found
      less belief in repressed memory among mainstream clinicians today compared with
      the 1990s. Groups that contained research-oriented psychologists and memory
      experts expressed more skepticism about the validity of repressed memories
      relative to other groups. Thus, a substantial gap between the memory beliefs of
      clinical-psychology researchers and those of practitioners persists today. These
      results hold implications for the potential resolution of the science-practice
      gap and for the dissemination of memory research in the training of mental-health
      professionals. 

PMID- 24335600
TI  - Fertile and selectively flirty: women's behavior toward men changes across the
      ovulatory cycle.
AB  - Past research shows that men respond to women differently depending on where
      women are in their ovulatory cycle. But what leads men to treat ovulating women
      differently? We propose that the ovulatory cycle alters women's flirting
      behavior. We tested this hypothesis in an experiment in which women interacted
      with different types of men at different points in their cycle. Results revealed
      that women in the ovulatory phase reported more interest in men who had purported
      markers of genetic fitness as short-term mates, but not as long-term mates.
      Furthermore, behavioral ratings of the interactions indicated that women
      displayed more flirting behaviors when they were at high than at low fertility.
      Importantly, fertile women flirted more only when interacting with men who had
      genetic-fitness markers, not with other men. In summary, fertility not only
      alters women's behavior but does so in a context-dependent way that follows
      adaptive logic. 

PMID- 24335601
TI  - Heart rate variability predicts control over memory retrieval.
AB  - Stopping retrieval of unwanted memories has been characterized as a process that
      requires inhibition. However, little research has examined the relationship
      between control over memory retrieval and individual differences in inhibitory
      control. Higher levels of resting heart rate variability (HRV) are associated
      with greater inhibitory control, as indicated by better performance on a number
      of cognitive, affective, and motor tasks. Therefore, we tested the hypothesis
      that higher levels of resting HRV predict enhanced memory inhibition as indexed
      by performance on the think/no-think task. Efforts to suppress no-think word
      pairs resulted in impaired recall for those items, as in past studies. Moreover,
      higher levels of resting HRV were associated with more successful suppression, as
      indicated by lower recall of the to-be-avoided stimuli relative to baseline
      stimuli. These findings are among the first to suggest that physiological markers
      of inhibitory control can be used to index a person's capacity to control
      unwanted memories. 

PMID- 24335602
TI  - Stereotyping to infer group membership creates plausible deniability for
      prejudice-based aggression.
AB  - In the present study, participants administered painful electric shocks to an
      unseen male opponent who was either explicitly labeled as gay or stereotypically
      implied to be gay. Identifying the opponent with a gay-stereotypic attribute
      produced a situation in which the target's group status was privately inferred
      but plausibly deniable to others. To test the plausible deniability hypothesis,
      we examined aggression levels as a function of internal (personal) and external
      (social) motivation to respond without prejudice. Whether plausible deniability
      was present or absent, participants high in internal motivation aggressed at low
      levels, and participants low in both internal and external motivation aggressed
      at high levels. The behavior of participants low in internal and high in external
      motivation, however, depended on experimental condition. They aggressed at low
      levels when observers could plausibly attribute their behavior to prejudice and
      aggressed at high levels when the situation granted plausible deniability. This
      work has implications for both obstacles to and potential avenues for prejudice
      reduction efforts. 

PMID- 24335603
TI  - Residents of poor nations have a greater sense of meaning in life than residents
      of wealthy nations.
AB  - Using Gallup World Poll data, we examined the role of societal wealth for meaning
      in life across 132 nations. Although life satisfaction was substantially higher
      in wealthy nations than in poor nations, meaning in life was higher in poor
      nations than in wealthy nations. In part, meaning in life was higher in poor
      nations because people in those nations were more religious. The mediating role
      of religiosity remained significant after we controlled for potential third
      variables, such as education, fertility rate, and individualism. As Frankl (1963)
      stated in Man's Search for Meaning, it appears that meaning can be attained even
      under objectively dire living conditions, and religiosity plays an important role
      in this search. 

PMID- 24335604
TI  - Reward-based transfer from bottom-up to top-down search tasks.
AB  - Recent evidence has suggested that reward modulates bottom-up and top-down
      attentional selection and that this effect persists within the same task even
      when reward is no longer offered. It remains unclear whether reward effects
      transfer across tasks, especially those engaging different modes of attention. We
      directly investigated whether reward-based contingency learned in a bottom-up
      search task was transferred to a subsequent top-down search task, and probed the
      nature of the transfer mechanism. Results showed that a reward-related benefit
      established in a pop-out-search task was transferred to a conjunction-search
      task, increasing participants' efficiency at searching for targets previously
      associated with a higher level of reward. Reward history influenced search
      efficiency by enhancing both target salience and distractor filtering, depending
      on whether the target and distractors shared a critical feature. These results
      provide evidence for reward-based transfer between different modes of attention
      and strongly suggest that an integrated priority map based on reward information
      guides both top-down and bottom-up attention. 

PMID- 24335605
TI  - Deferred feedback sharply dissociates implicit and explicit category learning.
AB  - The controversy over multiple category-learning systems is reminiscent of the
      controversy over multiple memory systems. Researchers continue to seek paradigms
      to sharply dissociate explicit category-learning processes (featuring category
      rules that can be verbalized) from implicit category-learning processes
      (featuring learned stimulus-response associations that lie outside declarative
      cognition). We contribute a new dissociative paradigm, adapting the technique of
      deferred-rearranged reinforcement from comparative psychology. Participants
      learned matched category tasks that had either a one-dimensional, rule-based
      solution or a multidimensional, information-integration solution. They received
      feedback either immediately or after each block of trials, with the feedback
      organized such that positive outcomes were grouped and negative outcomes were
      grouped (deferred-rearranged reinforcement). Deferred reinforcement qualitatively
      eliminated implicit, information-integration category learning. It left intact
      explicit, rule-based category learning. Moreover, implicit-category learners
      facing deferred-rearranged reinforcement turned by default and information
      processing necessity to rule-based strategies that poorly suited their nominal
      category task. The results represent one of the strongest explicit-implicit
      dissociations yet seen in the categorization literature. 

PMID- 24335606
TI  - Suppression of type III effector secretion by polymers.
AB  - Bacteria secrete effector proteins required for successful infection and
      expression of toxicity into host cells. The type III secretion apparatus is
      involved in these processes. Previously, we showed that the viscous polymer
      polyethylene glycol (PEG) 8000 suppressed effector secretion by Pseudomonas
      aeruginosa. We thus considered that other viscous polymers might also suppress
      secretion. We initially showed that PEG200 (formed from the same monomer
      (ethylene glycol) as PEG8000, but which forms solutions of lower viscosity than
      the latter compound) did not decrease effector secretion. By contrast, alginate,
      a high-viscous polymer formed from mannuronic and guluronic acid, unlike PEG8000,
      effectively inhibited secretion. The effectiveness of PEG8000 and alginate in
      this regard was closely associated with polymer viscosity, but the nature of
      viscosity dependence differed between the two polymers. Moreover, not only the
      natural polymer alginate, but also mucin, which protects against infection,
      suppressed secretion. We thus confirmed that polymer viscosity contributes to the
      suppression of effector secretion, but other factors (e.g. electrostatic
      interaction) may also be involved. Moreover, the results suggest that regulation
      of bacterial secretion by polymers may occur naturally via the action of
      components of biofilm or mucin layer. 

PMID- 24335608
TI  - The risk of toxicities from trastuzumab, alone or in combination, in an elderly
      breast cancer population.
AB  - BACKGROUND: Breast cancer in the elderly is associated with high recurrence and
      death rates, due mostly to undertreatment. Human epidermal growth factor receptor
      type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based
      chemotherapy is often withheld from elderly patients because of its
      cardiotoxicity. PATIENTS AND METHODS: Medical records of consecutive HER2
      positive breast cancer patients aged >=70 years old treated between 2005 and 2010
      in the participating centers were retrospectively reviewed. All patients
      underwent multidimensional geriatric assessment (MGA). RESULTS: Among 59 patients
      identified, 51 patients were evaluable (median age 76 years). The rate of any
      adverse event was 20% (10/51). The most relevant cardiac adverse event consisted
      of symptomatic congestive heart failure (CHF; n = 1, 2%) followed by asymptomatic
      decreases of left ventricular ejection fraction (LVEF; n = 6, 12%). Other
      toxicities included moderate hypersensitivity reactions during trastuzumab
      infusions (n = 3, 6%). Hypertension, obesity, prior anthracyclines exposure and
      concurrent chemotherapy were associated with a higher incidence of toxic events.
      Previous radiotherapy, concurrent endocrine therapy and different trastuzumab
      based regimens did not seem to influence toxicity. CONCLUSIONS: Our data suggest
      that trastuzumab has a good safety profile in nonfrail women aged 70 years and
      older. These favorable findings may be related to a limited number of
      anthracycline pretreatments, patient selection and a close cardiologic
      monitoring.

PMID- 24335607
TI  - Assessment of viral community functional potential from viral metagenomes may be
      hampered by contamination with cellular sequences.
AB  - Although the importance of viruses in natural ecosystems is widely acknowledged,
      the functional potential of viral communities is yet to be determined. Viral
      genomes are traditionally believed to carry only those genes that are directly
      pertinent to the viral life cycle, though this view was challenged by the
      discovery of metabolism genes in several phage genomes. Metagenomic approaches
      extended these analyses to a community scale, and several studies concluded that
      microbial and viral communities encompass similar functional potentials. However,
      these conclusions could originate from the presence of cellular DNA within viral
      metagenomes. We developed a computational method to estimate the proportion and
      origin of cellular sequences in a set of 67 published viromes. A quarter of the
      datasets were found to contain a substantial amount of sequences originating from
      cellular genomes. When considering only viromes with no cellular DNA detected,
      the functional potential of viral and microbial communities was found to be
      fundamentally different-a conclusion more consistent with the actual picture
      drawn from known viruses. Yet a significant number of cellular metabolism genes
      was still retrieved in these viromes, suggesting that the presence of auxiliary
      genes involved in various metabolic pathways within viral genomes is a general
      trend in the virosphere. 

PMID- 24335609
TI  - HIV transmission risk behaviors among people living with HIV/AIDS: the need to
      integrate HIV prevention interventions and public health strategies into HIV
      care.
AB  - CONTEXT: People living with human immunodeficiency virus (HIV)/AIDS (PLWHA) who
      continue high-risk behaviors may represent an important source for transmitting
      HIV infections. OBJECTIVE: To identify factors associated with high-risk
      behaviors among PLWHA and to plan better HIV prevention intervention strategies
      in HIV care. DESIGN: A cross-sectional survey to assess HIV transmission risk
      behaviors including sexual practices, disclosure of HIV infection status to
      sexual partner(s), and injection drug use. SETTING: Five HIV outpatient clinics
      serving diverse PLWHA in south central Pennsylvania. PARTICIPANTS: A total of 519
      HIV-infected patients. MAIN OUTCOME MEASURES: Two high-risk behaviors that may
      increase HIV transmission risk: (1) any unsafe sexual behavior and (2)
      nondisclosure of HIV infection status to sexual partner(s). An unsafe sexual
      behavior was defined as inconsistent condom use, sex under the influence of
      alcohol or drugs, or exchange of sex for money. A subgroup analysis was performed
      to examine factors related to unprotected anal intercourse among sexually active
      men who have sex with men. RESULTS: About two-thirds of 519 HIV patients (65.7%)
      were sexually active, and nearly 50% of sexually active patients reported at
      least 1 unsafe sexual behavior. Nondisclosure of HIV infection status was
      reported by about 15% of the patients. Partners' characteristics including HIV
      infection status and the perceived partner behavior (ie, partner may have sex
      with other people) were significantly associated with unsafe sexual behaviors and
      with nondisclosure of HIV infection status. Non-Hispanic black males were more
      likely to withhold their HIV infection status from their sexual partner(s)
      (adjusted odds ratio = 4.51) than their white counterparts. In addition, the
      perceived partner sexual behavior was significantly related to unprotected anal
      intercourse among men who have sex with men (adjusted odds ratio = 2.00).
      CONCLUSIONS: High-risk sexual behaviors are commonly reported by PLWHA, and these
      behaviors may be influenced by their partners' characteristics. HIV prevention
      interventions and public health strategies need to be incorporated into HIV care.

PMID- 24335610
TI  - HIV testing in US tuberculosis care settings: a survey of current practice and
      perceived barriers.
AB  - CONTEXT: Extent of and challenges to implementation of the Centers for Disease
      Control and Prevention (CDC) 2006 recommendation for routine HIV testing have not
      been reviewed specifically within tuberculosis (TB) care settings. OBJECTIVE: To
      determine current adherence to the CDC's HIV testing recommendations in TB care
      settings and identify barriers. DESIGN: An online survey was designed and
      distributed via Survey Monkey. SETTING: The 2011 National TB Conference
      attendees, National TB Nurse Controllers, and the CDC's TB-educate mailing list
      were invited to participate via e-mail. PARTICIPANTS: A total of 153 respondents
      from US states: 30 physicians, 91 nurses, 19 public health practitioners, and 13
      other. MAIN OUTCOME MEASURES: Perceived importance of HIV testing, current HIV
      testing practices, perceived barriers to HIV testing, and understanding of state
      HIV testing laws. RESULTS: One hundred forty-one of 153 (92.2%) reported that
      patients with TB disease were "always" or "almost always" HIV tested; 65 of 153
      (42.5%) reported the same for patients with latent TB infection (LTBI). Among
      those not routinely testing LTBI patients, "patient refusal of test" (53/88;
      60.2%), "cost" (41/88; 46.6%), and "prevalence too low to justify" (33/88; 37.5%)
      were the most commonly identified barriers to opt-out testing. Forty-seven of 59
      providers (79.7%) who reported that their state required written consent for HIV
      testing had incorrect knowledge regarding HIV testing legislation. CONCLUSIONS:
      Rates of HIV testing are high for patients with TB disease, but fewer than half
      of providers' care settings routinely test LTBI patients. Knowledge of HIV status
      is required to appropriately interpret TST results and make decisions regarding
      treatment in TB infection, since HIV coinfection increases risk of progression to
      active TB. Lack of HIV testing in LTBI patients represents a missed opportunity
      to prevent TB disease and its resultant morbidity and mortality. In addition,
      incorrect knowledge regarding testing legislation was a common problem among our
      TB providers. Further work is necessary to improve HIV testing rates in patients
      who have not yet progressed to active TB disease.

PMID- 24335611
TI  - Simultaneous electrophysiological recording and calcium imaging of
      suprachiasmatic nucleus neurons.
AB  - Simultaneous electrophysiological and fluorescent imaging recording methods were
      used to study the role of changes of membrane potential or current in regulating
      the intracellular calcium concentration. Changing environmental conditions, such
      as the light-dark cycle, can modify neuronal and neural network activity and the
      expression of a family of circadian clock genes within the suprachiasmatic
      nucleus (SCN), the location of the master circadian clock in the mammalian brain.
      Excitatory synaptic transmission leads to an increase in the postsynaptic Ca(2+)
      concentration that is believed to activate the signaling pathways that shifts the
      rhythmic expression of circadian clock genes. Hypothalamic slices containing the
      SCN were patch clamped using microelectrodes filled with an internal solution
      containing the calcium indicator bis-fura-2. After a seal was formed between the
      microelectrode and the SCN neuronal membrane, the membrane was ruptured using
      gentle suction and the calcium probe diffused into the neuron filling both the
      soma and dendrites. Quantitative ratiometric measurements of the intracellular
      calcium concentration were recorded simultaneously with membrane potential or
      current. Using these methods it is possible to study the role of changes of the
      intracellular calcium concentration produced by synaptic activity and action
      potential firing of individual neurons. In this presentation we demonstrate the
      methods to simultaneously record electrophysiological activity along with
      intracellular calcium from individual SCN neurons maintained in brain slices. 

PMID- 24335612
TI  - In vitro and in vivo antiangiogenic activity of caged polyprenylated xanthones
      isolated from Garcinia hanburyi Hook. f.
AB  - Eleven known caged polyprenylated xanthones 1-11 were isolated from the resin of
      Garcinia hanburyi Hook. f., and their structures were identified by their MS, NMR
      and UV spectra. These xanthones showed significant cytotoxicities against four
      human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) and strong inhibition
      against the proliferation of the HUVEC cell line in vitro by the MTT method.
      Furthermore, in an in vivo zebrafish model, xanthones 3 (morellic acid), 7
      (gambogenin) and 9 (isogambogenic acid) showed comparable antiangiogenic
      activities with less toxicities than xanthone 1 (gambogic acid), as evaluated by
      death and heart rates of treated zebrafish. Xanthone 7 exhibited antiangiogenic
      activity with no toxicity at concentrations ranging from 8 uM to 16 uM.
      Meanwhile, xanthones 1, 3, 7 and 9 strongly inhibited the migration of HUVEC at a
      low concentration of 0.5 uM in HUVEC cell migration assay in vitro. Taken
      together, these findings strongly suggest that xanthone 7 might be a novel
      angiogenesis inhibitor. 

PMID- 24335613
TI  - A novel cardiac bio-marker: ST2: a review.
AB  - Cardiovascular diseases (CVD) are the major cause of death worldwide. The
      identification of markers able to detect the early stages of such diseases and/or
      their progression is fundamental in order to adopt the best actions in order to
      reduce the worsening of clinical condition. Brain natriuretic peptide (BNP) and
      NT-proBNP are the best known markers of heart failure (HF), while troponins
      ameliorated the diagnosis of acute and chronic coronary artery diseases.
      Nevertheless, many limitations reduce their accuracy. Physicians have tried to
      develop further detectable molecules in order to improve the detection of the
      early moments of CVD and prevent their development. Soluble ST2 (suppression of
      tumorigenicity 2) is a blood protein confirmed to act as a decoy receptor for
      interleukin-33. It seems to be markedly induced in mechanically overloaded
      cardiac myocytes. Thus, HF onset or worsening of a previous chronic HF status,
      myocardial infarct able to induce scars that make the myocardium unable to
      stretch well, etc, are all conditions that could be detected by measuring blood
      levels of soluble ST2. The aim of this review is to explore the possible role of
      ST2 derived-protein as an early marker of cardiovascular diseases, above all in
      heart failure and ischemic heart diseases. 

PMID- 24335614
TI  - Discrimination of multi-origin chinese herbal medicines using gas chromatography
      mass spectrometry-based fatty acid profiling.
AB  - Multi-origin Chinese herbal medicines, with herbs originating from more than one
      species of plants, is a common phenomenon but an important issue in Traditional
      Chinese Medicines (TCMs). In the present study, a gas chromatography-mass
      spectrometry (GC-MS)-based fatty acid profiling approach to rapidly discriminate
      multi-origin Chinese medicines in terms of species and medicinal parts was
      proposed and validated using tuberous roots (Curcumae Radix) and rhizomes
      (Curcumae Rhizoma and Curcumae Longae Rhizoma) derived from four Curcuma species
      (e.g., C. wenyujin, C. kwangsiensis, C. phaeocaulis and C. longa) as models. Both
      type and content of fatty acids varied among different species of either tuberous
      roots or rhizomes, indicating each species has its own fatty acid pattern.
      Orthogonal partial least squares discriminant analysis (OPLS-DA) and hierarchical
      clustering analysis (HCA) based on dataset of global fatty acid profiling showed
      that either tuberous roots or rhizomes samples could be clearly classified into
      four clusters according to their species. Furthermore, those tested samples could
      also be discriminated in terms of their medicinal parts (e.g., tuberous root and
      rhizome). Our findings suggest that the proposed GC-MS-based fatty acid profiling
      followed by multivariate statistical analysis provides a reliable platform to
      discriminate multi-origin Chinese herbal medicines according to species and
      medicinal parts, which will be helpful for ensuring their quality, safety and
      efficacy. 

PMID- 24335615
TI  - Identification and physicochemical characteristics of temozolomide process
      related impurities.
AB  - In this article the crystal structures of the starting material TZ-5 and the key
      intermediate TZ-6 of temozolomide (TZ-7), an anticancer therapeutic agent, are
      presented, together with their spectroscopic and thermal characteristics. Both
      compounds crystallize in the triclinic P-1 space group. X-ray crystallography
      studies proved that the compound TZ-6 exists as a monohydrate. A complete
      structural assignment was obtained for the signals in the 1H-, 13C- and 15N
      nuclear magnetic resonance spectra and the structures were confirmed by Fourier
      Transform infrared and Raman spectroscopy. The article describes the importance
      of the high purity of TZ-6 during the small-scale plant production of TZ-7 in a
      desired polymorphic form III with the purity higher than 99.50%, according to an
      HPLC method. 

PMID- 24335616
TI  - Fluorescent probes for nucleic Acid visualization in fixed and live cells.
AB  - This review analyses the literature concerning non-fluorescent and fluorescent
      probes for nucleic acid imaging in fixed and living cells from the point of view
      of their suitability for imaging intracellular native RNA and DNA. Attention is
      mainly paid to fluorescent probes for fluorescence microscopy imaging.
      Requirements for the target-binding part and the fluorophore making up the probe
      are formulated. In the case of native double-stranded DNA, structure-specific and
      sequence-specific probes are discussed. Among the latest, three classes of dsDNA
      targeting molecules are described: (i) sequence-specific peptides and proteins;
      (ii) triplex-forming oligonucleotides and (iii) polyamide oligo(N-methylpyrrole/N
      methylimidazole) minor groove binders. Polyamides seem to be the most promising
      targeting agents for fluorescent probe design, however, some technical problems
      remain to be solved, such as the relatively low sequence specificity and the high
      background fluorescence inside the cells. Several examples of fluorescent probe
      applications for DNA imaging in fixed and living cells are cited. In the case of
      intracellular RNA, only modified oligonucleotides can provide such sequence
      specific imaging. Several approaches for designing fluorescent probes are
      considered: linear fluorescent probes based on modified oligonucleotide analogs,
      molecular beacons, binary fluorescent probes and template-directed reactions with
      fluorescence probe formation, FRET donor-acceptor pairs, pyrene excimers,
      aptamers and others. The suitability of all these methods for living cell
      applications is discussed. 

PMID- 24335617
TI  - Bortezomib congeners induce apoptosis of hepatocellular carcinoma via CIP2A
      inhibition.
AB  - CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell
      proliferation and survival. The proteasome inhibitor bortezomib has been shown to
      reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group
      of bortezomib to generate a series of novel compounds and conducted a structure
      activity relationship (SAR) study. The results showed that compound 1 was able to
      repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but
      with less potency in inhibition of proteasome activity. This finding provides a
      new direction for the design of CIP2A inhibitors. 

PMID- 24335618
TI  - A triple staining method for accurate cell cycle analysis using multiparameter
      flow cytometry.
AB  - Cell cycle analysis is important for cancer research. We present herein a novel
      method for accurate cell cycle analysis. This method analyzes the cell cycle by
      multiparameter flow cytometry based on simultaneously labeling the cell nuclear
      DNA, RNA, and phosphorylated mitotic nuclei protein, using Hoechst 33342, pyronin
      Y, and MPM-2-Cy5, respectively, and our results demonstrated that this method
      could effectively divide the cell cycle into G0, G1, S, G2, and M phases. We
      further tested this method using the clinical anticancer agents crizotinib and
      taxol, and the results clearly illustrated that crizotinib and taxol arrested
      Jurkat cells in G0 and M phase, respectively. These results indicate that this
      method could be a very useful tool for cytokinetic and pharmacological research. 

PMID- 24335619
TI  - Highly enantioselective addition of phenylethynylzinc to aldehydes catalyzed by
      chiral cyclopropane-based amino alcohols.
AB  - The enantioselective addition of phenylethynylzinc to aldehydes catalyzed by a
      series of cyclopropane-based amino alcohol ligands 7 was investigated. The
      reactions afforded chiral propargylic alcohols in high yields (up to 96%) and
      with excellent enantioselectivities (up to 98% ee) under mild conditions.
      Furthermore, studies on the structural relationship show that the matching of the
      chiral center configuration is crucial to obtain the high enantioselectivity. 

PMID- 24335620
TI  - G-quadruplex guanosine gels and single walled carbon nanotubes.
AB  - Solubilization of single walled carbon nanotubes (SWNTs) in aqueous gel phases
      formed by reversible, G-quadruplex self-assembly of guanosine monophosphate (GMP)
      alone or with guanosine (Guo) is described. Unlike other media and methods for
      aqueous solubilization of SWNTs, the guanosine gels ("G-gels") are found to
      readily disperse high (>mg/mL) concentrations of individual rather than bundled
      SWNTs. SWNT dispersions in GMP alone precipitate in several hours and re-form
      upon shaking; however, dispersions in the binary GMP/Guo gels are indefinitely
      stable. Increasing GMP or KCl concentration in the binary gels increased the
      relative abundance of large diameter and semi-conducting SWNTs. Different gel
      compositions also displayed different selectivities toward SWNTs of different
      chiralities. These results indicate a strong connection between the self
      assembled G-gels and the dimensions and structures of the SWNTs that they
      solubilize. 

PMID- 24335622
TI  - Hysterectomy in obese patients: special considerations.
AB  - A literature search was performed to find evidence-based practices that aid in
      the preoperative evaluation, intraoperative techniques, and postoperative
      management of the obese patient requiring hysterectomy. Complications are more
      frequent than in normal weight patients and are more difficult to manage. Few
      studies provide direct evidence with which to help guide surgical decision-making
      and postoperative management. However, there is sufficient evidence to support
      that when feasible, the vaginal route is preferable in obese patients. Techniques
      validated for normal weight patients like antibiotic and thromboembolism
      prophylaxis seem effective in obese patients, and are likely even more important.

PMID- 24335621
TI  - 'Essential tremor' or 'the essential tremors': is this one disease or a family of
      diseases?
AB  - There is accumulating evidence that the entity referred to as 'essential tremor'
      (ET) is not a single disease. It may be a family of diseases better referred to
      as 'the ETs'. This review will summarize the following evidence: (1) the presence
      of etiological heterogeneity; (2) the heterogeneity of findings in postmortem
      studies, thus suggesting several diseases; (3) the recent discussion that age of
      onset may be an important marker of disease heterogeneity; (4) the clinical
      expansion of the concept of ET in recent years to include a broader range of
      tremor phenomenology, other motor features (gait ataxia), other involuntary
      movements (dystonia), and nonmotor features (cognitive problems, psychiatric
      problems), some of which could be primary; (5) the heterogeneity of
      pharmacological response profiles and clinical progression, and (6) the
      association of ET with Parkinson's disease, Alzheimer's disease, and possibly
      progressive supranuclear palsy, with the possibility that some ET patients are
      more predisposed to develop one of these. (c) 2013 S. Karger AG, Basel. 

PMID- 24335623
TI  - TFAP2A regulates nasopharyngeal carcinoma growth and survival by targeting HIF
      1alpha signaling pathway.
AB  - TFAP2A is a transcription factor that orchestrates a variety of cell processes,
      including cell growth and tissue differentiation. However, the regulation of
      TFAP2A in human nasopharyngeal carcinoma tumorigenesis and its precise mechanism
      of action remain largely unknown. In this study, we investigated the biologic
      role and clinical significance of TFAP2A in nasopharyngeal carcinoma growth and
      progression and identified the underlying molecular mechanisms. We found that
      TFAP2A was highly expressed in various nasopharyngeal carcinoma cell lines and
      tumor tissue specimens and was significantly correlated with hypoxia-inducible
      factor-1alpha (HIF-1alpha) expression. A positive correlation of TFAP2A
      overexpression with advanced tumor stage, local invasion, clinical progression,
      and poor prognosis of patients with nasopharyngeal carcinomas were also observed.
      Moreover, we found that knockdown of TFAP2A expression by siRNA significantly
      inhibited tumor cell growth in nasopharyngeal carcinoma cell lines and in a
      subcutaneous xenograft mouse model by targeting the HIF-1alpha-mediated
      VEGF/pigment epithelium-derived factor (PEDF) signaling pathway. Treatment of
      nasopharyngeal carcinoma cells with TFAP2A siRNA dramatically inhibited the
      expression and the release of VEGF protein but did not change the level of PEDF
      protein, resulting in a significant reduction of the ratio of VEGF/PEDF.
      Pretreatment with a HIF-1alpha siRNA did not significantly change the TFAP2A
      siRNA-mediated inhibition in cell viability. Our results indicate that TFAP2A
      regulates nasopharyngeal carcinoma growth and survival through the modulation of
      the HIF-1alpha-mediated VEGF/PEDF signaling pathway, and suggest that TFAP2A
      could be a potential prognostic biomarker and therapeutic target for
      nasopharyngeal carcinoma treatment.

PMID- 24335628
TI  - Very late complications of cervical arthroplasty: results of 2 controlled
      randomized prospective studies from a single investigator site.
AB  - STUDY DESIGN: Prospective, single-site, randomized, Food and Drug Administration
      approved investigational device exemption clinical trials of 2 cervical
      arthroplasty (CA) devices. OBJECTIVE: To evaluate complications with CA occurring
      more than 4 years after the surgical procedure in Food and Drug Administration
      clinical trials of the Bryan and Prestige LP arthroplasty devices. SUMMARY OF
      BACKGROUND DATA: Reports of several randomized clinical studies have shown CA to
      be a safe and effective alternative to anterior cervical fusion in the treatment
      of degenerative cervical disc disorders. A majority include follow-up intervals
      of 4 years or less. METHODS: Between 2002 and 2006, 94 patients were enrolled in
      Food and Drug Administration studies of the Bryan and Prestige LP cervical disc
      devices. Charts, imaging studies, and hospital records were reviewed for those
      who underwent arthroplasty and returned more than 4 years after their surgical
      procedure with neck-related pain or dysfunction. RESULTS: Excluding adjacent
      segment disease that occurred with a similar rate for patients who underwent
      fusion and arthroplasty, 5 patients, all treated with arthroplasty, returned for
      evaluation of neck and arm symptoms between 48 and 72 months after surgery. Four
      patients had peridevice vertebral body bone loss. One patient had posterior
      device migration and presented with myelopathy. Three required revision surgery
      and 2 were observed. Four patients maintained follow-up and reported
      stabilization or improvement in symptoms. CONCLUSION: Despite their similarities,
      CA and fusion are not equivalent procedures in this study in regard to very late
      complications. Similar to large joint arthroplasty, delayed device-related
      complications may occur with CA. These complications commenced well beyond the
      time frame for complications associated with more traditional cervical spine
      procedures. Both patients and surgeons should be aware of the potential for very
      late device-related complications occurring with CA and the need for revision
      surgery. LEVEL OF EVIDENCE: 1.

PMID- 24335629
TI  - Clinical outcomes with selectively constrained SECURE-C cervical disc
      arthroplasty: two-year results from a prospective, randomized, controlled,
      multicenter investigational device exemption study.
AB  - STUDY DESIGN: Prospective, multicenter, randomized, and controlled
      Investigational Device Exemption clinical trial. OBJECTIVE: To compare the
      clinical safety and effectiveness of the selectively constrained SECURE-C (Globus
      Medical, Audubon, PA) Cervical Artificial Disc to anterior cervical discectomy
      and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Cervical total disc replacement
      has been developed as an alternative to ACDF by allowing segmental motion.
      Current cervical total disc replacement designs incorporate constrained and
      unconstrained metal-on-metal or metal-on-polymer articulating designs with
      various means of fixation. METHODS: A total of 380 patients from 18
      investigational sites were prospectively enrolled in the study. Patients were
      randomized, treated surgically, and evaluated postoperatively at 6 weeks, 3
      months, 6 months, 12 months, and 24 months. Clinical outcomes include overall
      success, visual analogue scale pain (right arm, left arm, and neck), neck
      disability index, neurological status, Short Form 36 (SF-36) Health Status Survey
      questionnaires, range of motion, and adverse events. Bayesian statistical methods
      were used to analyze the outcomes. RESULTS: Overall success results demonstrated
      statistical superiority of the randomized SECURE-C group compared with the
      randomized ACDF group at 24 months, with a posterior probability of 100% using
      the protocol-specified criteria and 98.1% using Food and Drug Administration
      defined criteria. At 24 months postoperatively, SECURE-C demonstrated clinically
      significant improvement in pain and function in terms of neck disability index,
      visual analogue scale, and 36-Item Short Form Health Survey. At 24 months, the
      percentage of patients experiencing secondary surgical interventions at the index
      level was statistically lower for the SECURE-C group (2.5%) than the ACDF group
      (9.7%). At 24 months, 84.6% of as-treated SECURE-C patients were range-of-motion
      successes. Satisfaction was high among SECURE-C patients. CONCLUSION: The
      selectively constrained SECURE-C Cervical Artificial Disc is as safe and
      effective as the standard of care, an anterior cervical discectomy and fusion.
      SECURE-C is statistically superior in terms of overall success, index-level
      subsequent surgical procedures, and patient satisfaction, making it an attractive
      surgical option for patients with symptomatic cervical disc disease. LEVEL OF
      EVIDENCE: 1.

PMID- 24335630
TI  - Effect of type II odontoid fracture nonunion on outcome among elderly patients
      treated without surgery: based on the AOSpine North America geriatric odontoid
      fracture study.
AB  - STUDY DESIGN: Subgroup analysis of a prospective multicenter study. OBJECTIVE:
      Outcome analysis of nonoperatively treated elderly patients with type II odontoid
      fractures, including assessment of consequence of a fracture nonunion. SUMMARY OF
      BACKGROUND DATA: Odontoid fractures are among the most common fractures in the
      elderly, and controversy exists regarding treatment. METHODS: Subgroup analysis
      of a prospective multicenter study of elderly patients (>=65 yr) with type II
      odontoid fracture. Neck Disability Index and Short-Form 36 (SF-36) version 2 were
      collected at baseline and 6 and 12 months. Fifty-eight (36.5%) of the 159
      patients were treated nonoperatively. RESULTS: Of the 58 patients initially
      treated nonoperatively, 8 died within 90 days and were excluded. Of the remaining
      50 patients, 11 (22.0%) developed nonunion, with 7 (63.6%) requiring surgery.
      Four of the 39 (10.3%) patients classified as having "successful union" required
      surgery due to late fracture displacement. Thus, 15 (30.0%) patients developed
      primary or secondary nonunion and 11 (22.0%) required surgery. The overall 12
      month mortality was 14.0% (nonunion = 2, union = 5; P= 0.6407). For union and
      nonunion groups, Neck Disability Index and SF-36 version 2 declined significantly
      at 12 months compared with preinjury values (P< 0.05), except for SF-36 version 2
      Physical Functioning (P= 0.1370). There were no significant differences in
      outcome parameters based on union status at 12 months (P> 0.05); however, it is
      important to emphasize that the 12-month outcomes for the nonunion patients
      reflect the status of the patient after delayed surgical treatment in the
      majority of these cases. CONCLUSION: Nonoperative treatment for type II odontoid
      fracture in the elderly has high rates of nonunion and mortality. Patients with
      nonunion did not report worse outcomes compared with those who achieved union at
      12 months; however, the majority of patients with nonunion required delayed
      surgical treatment. These findings may prove useful for patients who are not
      surgical candidates or elect for nonoperative treatment. LEVEL OF EVIDENCE: 2.

PMID- 24335631
TI  - Rate of adjacent segment disease in cervical disc arthroplasty versus single
      level fusion: meta-analysis of prospective studies.
AB  - STUDY DESIGN: Meta-analysis of randomized controlled trials. OBJECTIVE: To
      compare the reported incidence of adjacent segment disease (ASD) requiring
      surgical intervention between anterior cervical decompression and fusion (ACDF)
      and total disc arthroplasty (TDA). SUMMARY OF BACKGROUND DATA: The concern for
      ASD has led to the development of motion-preserving technologies such as TDA. To
      date, however, no known study has sought to compare the incidence of ASD between
      ACDF and TDA in major prospective studies. METHODS: A systematic review of IDE
      and non-IDE trials was performed using PubMed and Cochrane libraries. These
      databases were thoroughly searched for prospective randomized studies comparing
      ACDF and TDR. Six studies met the inclusion criteria for a meta-analysis and were
      used to report an overall rate of ASD for both ACDF and TDA. RESULTS: Pooling
      data from 6 prospective studies, the overall sample size at baseline was 1586
      (ACDF = 777, TDA = 809) and at the final follow-up was 1110 giving an overall
      follow-up of 70%. Patients after an ACDF had a lower rate of follow-up overall
      than those after TDR (ACDF: 67.3% vs. TDR: 72.6%, P= 0.01). Thirty-six patients
      required adjacent-level surgery after an ACDF at 2 to 5 years of follow-up (6.9%)
      compared with 30 patients after a TDA (5.1%). The corresponding reoperation rate
      for ASD was 2.4 +/- 1.7% per year for ACDF versus 1.1 +/- 1.5% per year for TDR.
      These differences were not statistically significant (P= 0.44). Using a Kaplan
      Meier analysis and historical data, we expect 48 patients in the ACDF group and
      55 patients in the TDR group to have symptomatic disease at an adjacent level.
      CONCLUSION: From a meta-analysis of prospective studies, there is no difference
      in the rate of ASD for ACDF versus TDA. We also report an overall lower rate of
      follow-up for patients with ACDF than for those with TDR. Future prospective
      studies should continue to focus on excellent patient follow-up and accurate
      assessment of patient symptoms that are attributable to an adjacent level as this
      has been an under-reported finding in prospective studies. LEVEL OF EVIDENCE: 1.

PMID- 24335632
TI  - Foot drop caused by single-level disc protrusion between T10 and L1.
AB  - STUDY DESIGN: Retrospective investigation of surgical treatment of 25 patients
      with foot drop from single-level disc protrusion in the region of T10 to L1.
      OBJECTIVE: To describe cases of foot drop from single-level disc protrusion in
      the region of T10 to L1 and surgical outcomes. SUMMARY OF BACKGROUND DATA: Three
      cases of foot drop from T12-L1 disc protrusion are reported in the literature.
      Little is known, however, about foot drop resulting from single-level disc
      protrusion between T10 and L1 or its surgical outcomes. METHODS: Between January
      1995 and October 2010, a total of 25 patients (mean age: 44 yr; range, 21-68 yr)
      presented to our department with single-level disc protrusion between T10 and L1
      (6 at T10-T11, 7 at T11-T12, and 12 at T12-L1) with associated foot drop and
      without cervical or lumbar spinal stenosis or other neurological disease. The
      average follow-up period was 46.5 months. We treated all cases surgically with
      circumferential decompression with fixation. We assessed neurological status,
      tibialis anterior muscle strength, magnitude of local kyphosis, and cross
      sectional area at the level of compression of the dural sac preoperatively and at
      the final follow-up. RESULTS: Preoperatively, all 25 patients exhibited both foot
      drop resulting from a lower motor neuron lesion and pathological reflexes
      resulting from an upper motor neuron lesion. Postoperatively, the mean calculated
      muscle strength recovery rate was 95%. Mean Japanese Orthopaedic Association
      score increased from 5.92 +/- 1.22 points preoperatively to 9.56 +/- 0.92 points
      at the final follow-up. Magnetic resonance imaging indicated that the cross
      sectional area increased from 36.3 +/- 7.3 mm2 preoperatively to 133.1 +/- 6.1
      mm2 postoperatively. CONCLUSION: Foot drop can be caused by single-level disc
      protrusion between T10 and L1 and is usually associated with an upper motor
      neuron lesion. Pathological reflexes resulting from disc protrusion occurring
      between T10 and L1 differ depending on the level of the protrusion.
      Circumferential decompression with fixation may be an effective treatment option
      for this syndrome. LEVEL OF EVIDENCE: 4.

PMID- 24335633
TI  - Re: Nieuwenhuijse MJ, Bollen L, van Erkel AR, et al. Optimal intravertebral
      cement volume in percutaneous vertebroplasty for painful osteoporotic vertebral
      compression fractures. Spine 2012;37:1747-55.

PMID- 24335634
TI  - In response.

PMID- 24335635
TI  - Hyperbaric oxygen alleviates experimental (spinal cord) injury by downregulating
      HMGB1/NF-kappaB expression.
AB  - STUDY DESIGN: We presented an insight into the effect of hyperbaric oxygen (HBO)
      on spinal cord injury (SCI), aiming to uncover the dynamics of high-mobility
      group protein B1 (HMGB1) and nuclear factor kappaB (NF-kappaB) after HBO
      intervention in rats with acute SCI. OBJECTIVE: Prognosis of SCI is directly
      linked with the control of secondary injury, in which the inflammatory response
      plays a leading role. HBO therapy can reduce this secondary damage to the spinal
      cord. We used an animal model to characterize the therapeutic effect of HBO on
      SCI. SUMMARY OF BACKGROUND DATA: A growing number of studies have confirmed that
      HBO has gradually become an indispensable element after SCI in reducing
      neurological disorders, and improving the physical function and quality of life
      of patients. The role of HBO in the process of HMGB1/NF-kappaB-related secondary
      inflammatory responses in SCI has yet to be characterized. METHODS: Rats were
      randomly categorized into sham, sham + HBO, SCI, and SCI + HBO groups. The
      expression levels of HMGB1 and NF-kappaB were measured at days 1, 3, 7, and 14
      after SCI. RESULTS: After SCI, significant increases in mRNA and protein
      expression were observed for both HMGB1 and NF-kappaB (P< 0.01) compared with
      sham group. HMGB1 mRNA and protein expression levels were decreased after HBO
      intervention. The decreases were significant at days 7 and 14 (P< 0.05) post-HBO.
      In the SCI + HBO group, the significant decreases in NF-kappaB mRNA and protein
      expression levels were also observed at days 3, 7, and 14 (P< 0.05). After HBO
      intervention, a significant increase was seen in the Basso, Beattie, and
      Bresnahan score at days 7 and 14 (P< 0.05). CONCLUSION: HBO intervention may
      reduce the secondary damage of SCI caused by inflammatory responses via
      downregulating the expression of HMGB1/NF-kappaB, and promoting the repair of
      neurological function. LEVEL OF EVIDENCE: N/A.

PMID- 24335636
TI  - Effect of anterior mobilization and shortening in the correction of rigid
      idiopathic thoracic scoliosis.
AB  - STUDY DESIGN: Retrospective study of patients with anterior release and posterior
      correction instrumentation in a 2-stage procedure for rigid thoracic scoliosis.
      OBJECTIVE: To examine the effect of the anterior release and shortening alone as
      well as its role in the overall correction. SUMMARY OF BACKGROUND DATA: With
      segmental transpedicular instrumentation the need for an additional anterior
      mobilization became rare. However, its effect on sagittal profile was not
      sufficiently acknowledged. METHODS: Twenty-two patients with rigid thoracic
      scoliosis (Lenke 1A, n = 3; 2A, n = 6; 2B, n = 2; 2C, n = 1; 4B, n = 1; 4C, n = 9
      patients) were operated in a 2-stage procedure with anterior release followed by
      posterior correction. The anterior release included convex resection of the rib
      heads and shortening of the anterior column by resection of the discs and the
      convex anterolateral endplates in a mean of 8 (4-11) segments.After 14 days (6
      27), the posterior instrumentation and correction was done. RESULTS: The
      preoperative thoracic scoliosis measured a mean of 80 degrees , upper thoracic 42
      degrees , and lumbar 49 degrees . The thoracic curve corrected in bending 20
      degrees  (25%), upper thoracic 10 degrees  (24%), and lumbar 26 degrees  (53%).
      The mean thoracic kyphosis (T5-T12) was 11 degrees , lumbar lordosis was -41
      degrees .After the anterior release and shortening, thoracic scoliosis improved
      to 50 degrees , thoracic kyphosis increased to 32 degrees .After the posterior
      surgery the following values were noted: thoracic scoliosis 10 degrees , upper
      thoracic 9 degrees , lumbar 8 degrees , thoracic kyphosis 25 degrees , and lumbar
      lordosis -41 degrees . The results were maintained at follow-up. CONCLUSION:
      Anterior shortening results in a spontaneous correction of the thoracic scoliosis
      and hypokyphosis. In this series, the Cobb angle reduced 38% from a mean of 80
      degrees  to a mean of 50 degrees . Thoracic kyphosis increased from 11 degrees 
      to 32 degrees . This correction was achieved without any corrective force or
      instrumentation. The second-stage posterior correction is facilitated and nearly
      complete correction is achieved with a residual curve on average of 10 degrees 
      with a physiological sagittal profile. LEVEL OF EVIDENCE: 4.

PMID- 24335637
TI  - Radiographical predictors for postoperative sagittal imbalance in patients with
      thoracolumbar kyphosis secondary to ankylosing spondylitis after lumbar pedicle
      subtraction osteotomy.
AB  - STUDY DESIGN: A retrospective radiographical study. OBJECTIVE: To identify the
      radiographical predictors for sagittal imbalance in patients with thoracolumbar
      kyphosis secondary to ankylosing spondylitis (AS) after 1-level lumbar pedicle
      subtraction osteotomy (PSO). SUMMARY OF BACKGROUND DATA: Few studies had
      correlated the preoperative sagittal parameters with postoperative sagittal
      alignments to determine the radiographical predictors for postoperative sagittal
      imbalance in patients with AS after 1-level lumbar PSO. METHODS: Thirty-six
      patients with thoracolumbar kyphosis secondary to AS who underwent 1-level lumbar
      PSO were recruited with a minimal follow-up of 24 months (mean = 27.4 mo; range,
      24-53 mo). Correlation analysis and subsequent stepwise multiple regression
      analysis were used to evaluate the correlations between preoperative parameters,
      including global kyphosis, local kyphosis, thoracic kyphosis, thoracolumbar Cobb
      angle, lumbar lordosis, pelvic incidence (PI), pelvic tilt, sacral slope, and
      sagittal vertical axis (SVA), as well as SVA at the last follow-up. All these
      patients were further divided into 2 groups according to the PI value (group A:
      PI >50 degrees ; group B: PI <=50 degrees ). The correction outcomes were
      compared between these 2 groups. RESULTS: The preoperative SVA was not
      significantly different between group A and group B (157.6 mm vs. 124.5 mm; P>
      0.05), and both groups had similar magnitudes of kyphosis corrections at the last
      follow-up (global kyphosis: 42.9 degrees  vs. 46.1 degrees ; local kyphosis: 42.7
      degrees  vs. 40.5 degrees ; lumbar lordosis: 35.7 degrees  vs. 43.0 degrees ).
      However, group A patients had significantly larger SVA at the last follow-up
      (73.2 mm vs. 28.7 mm; P< 0.05) and a higher incidence of postoperative sagittal
      imbalance (77.8% vs. 25.9%; P< 0.05) than those in group B. The stepwise multiple
      regression analysis demonstrated that both preoperative SVA and PI were
      significant independent predictors of postoperative sagittal alignments, which
      explained 52.0% and 9.7% of the variability of SVA at the last follow-up,
      respectively. CONCLUSION: Patients with AS with either larger preoperative SVA or
      larger PI are more likely to experience failed sagittal realignments after 1
      level lumbar PSO. For these patients, additional osteotomies may be recommended
      for satisfactory correction outcomes. LEVEL OF EVIDENCE: 4.

PMID- 24335638
TI  - Sciatica and claudication caused by ganglion cyst.
AB  - STUDY DESIGN: Case report. OBJECTIVE: We report a rare case that a ganglion cyst
      compressed the sciatic nerve and caused sciatica and claudication in a 51-year
      old male. SUMMARY OF BACKGROUND DATA: Sciatica and claudication commonly occurs
      in spinal stenosis. To our knowledge, only 4 cases have been reported on sciatica
      resulting from posterior ganglion cyst of hip. METHODS: A 51-year-old male had a
      2-month history of radiating pain on his right leg. He could only walk 20 to 30 m
      before stopping and standing to rest for 1 to 3 minutes. Interestingly, he was
      able to walk longer distances (about 200 m) when walking slowly in small steps,
      without any rest. He had been treated as a case of lumbar disc herniation, but
      conservative treatment was ineffective. On buttock examination, a round, hard,
      and fixative mass was palpated at the exit of the sciatic nerve. MR imaging of
      hip revealed a multilocular cystic mass located on the posterior aspect of the
      superior gemellus and obturator internus, compressing the sciatic nerve. RESULTS:
      On operation, we found that the cyst extended to the superior gemellus and the
      obturator internus, positioned right at the outlet of the sciatic nerve. At 18
      months of follow-up, the patient continued to be symptom free. He returned to
      comprehensive physical activity with no limitations. CONCLUSION: For an
      extraspinal source, a direct compression on the sciatic nerve also resulted in
      sciatica and claudication. A meticulous physical examination is very important
      for the differential diagnosis of extraspinal sciatica from spinal sciatica.

PMID- 24335639
TI  - Cervical spinal cord injury after thoracic spinal instrumentation: a case series.
AB  - STUDY DESIGN: Retrospective case report of 2 cases. OBJECTIVE: To describe 2
      cases of cervical spinal cord injury/vascular insult after posterior
      instrumentation of thoracic/thoracolumbar scoliosis. SUMMARY OF BACKGROUND DATA:
      Spinal cord injury is an uncommon but well-documented complication associated
      with spinal deformity surgery. The midthoracic spinal cord is most vulnerable to
      these presumed vascular insults. Injuries above the level of instrumentation are
      rare. METHODS: In this report, we review the clinical histories of 2 adolescent
      females undergoing posterior spinal fusion with subsequent cervical spinal cord
      injuries. RESULTS: In both cases, intraoperative cervical alignment appeared
      neutral and all hardware appeared appropriately positioned. Spinal cord
      monitoring demonstrated changes in 1 patient but not in the other. With time,
      both patients improved clinically. CONCLUSION: Cervical spinal cord injuries may
      occur after distal deformity correction.

PMID- 24335640
TI  - Delayed distant spinal metastasis in thymomas.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To demonstrate 2 cases of delayed distant
      spinal metastasis from a thymoma with comprehensive immunohisto-chemical
      analysis. SUMMARY OF BACKGROUND DATA: Thymoma is a rare slow-growing cancer
      arising in the mediastinum. Thymomas usually grow invasively into surrounding
      structures. Distal spinal metastasis is uncommon. To date, only 4 cases with
      histological verification have been described. METHODS: Patient 1: A 42-year-old
      female complained about back pain for 4 years. She underwent gross-total
      resection of a type B2 thymoma 8 years earlier without adjuvant therapy.
      Neurological examination revealed no deficits. Magnetic resonance imaging
      demonstrated an intraspinal extradural tumor at the level of L4-S1 with
      infiltration of vertebral body L5. A nearly total resection was performed via a
      partial L4 and L5 hemilaminectomy.Patient 2: A 62-year-old female was referred
      with segmental thoracic pain. She underwent a total of 6 surgical procedures for
      resection of a thymic carcinoma during a period of 13 years with a subsequently
      local radiation therapy and various chemotherapy cycles. Magnetic resonance
      imaging revealed an intraspinal extradural tumor at the level of T9-T10 with
      infiltration of vertebral body T9-T10. A gross-total tumor resection was
      performed via a costotransversectomy and facetectomy T9-T10. RESULTS: Patient 1:
      The tumor cells were strongly positive for AE1/3- and CK5/14-specific antibodies.
      Most of the immature T-cells expressed CD3. CD1a, CD5, and TdT expression was
      observed in a smaller portion. The findings were consistent with the diagnosis of
      a spinal metastasis of the known type B2 thymoma.Patient 2: The tumor cells were
      CK5/14 and CK19/20 positive. Only the infiltrating lymphocytes were labeled with
      CD3-specific antibodies. Histopathological findings revealed a metastasis of a
      previously resected well-differentiated thymus carcinoma. CONCLUSION: We
      recommend surgical resection because metastasis of thymoma may infiltrate nerve
      roots and compress the spinal cord. A multidisciplinary approach is required to
      manage long-term sequelae.

PMID- 24335642
TI  - Cytokeratin 17: an adjunctive marker of invasion in squamous neoplastic lesions
      of the anus.
AB  - Diagnosing anal squamous cell carcinoma (SCC), which is often preceded by anal
      intraepithelial neoplasia (AIN), may be challenging in small biopsies.
      Cytokeratin 17 (CK17) is a basal/myoepithelial cell keratin induced in activated
      keratinocytes and associated with disease progression in SCC of the uterine
      cervix, esophagus, and oral cavity. We investigated the utility of CK17 in
      diagnosing invasion in anal squamous neoplastic lesions. Immunohistochemical
      staining for CK17 was evaluated in 11 AINs, 12 invasive SCCs, 8 invasive SCCs
      with basaloid features (BSCC), and 2 invasive pure basaloid carcinomas. The
      pattern of staining was scored as surface/central, peripheral/rim, diffuse, or
      absent. All cases of invasive SCC and BSCC stained positive for CK17. Eleven of
      12 (92%) SCCs showed diffuse staining, and 1 of 12 (8%) showed peripheral
      staining. Six of 8 (75%) BSCCs showed diffuse staining, and 2 of 8 (25%) showed
      peripheral staining. Both pure basaloid carcinomas were negative for CK17. One of
      11 (9%) AINs was diffusely positive for CK17; all other AINs had surface or
      absent CK17. Of the 6 patients with concurrent AIN and invasive carcinoma,
      superficial expression of CK17 was present in 1 AIN, whereas all invasive
      components showed diffuse staining. The sensitivity and specificity of CK17 for
      identifying invasion in SCC and BSCC was 100% and 91%, respectively. Peripheral
      or diffuse staining for CK17 is a useful marker of invasion in anal squamous
      neoplastic lesions. A potential pitfall in the utility of CK17 is that the pure
      basaloid variant of anal carcinoma is negative for CK17. 

PMID- 24335643
TI  - Basal cell carcinosarcoma with PTCH1 mutations in both epithelial and sarcomatoid
      primary tumor components and in the sarcomatoid metastasis.
AB  - Basal cell carcinosarcoma is a rare biphenotypic malignant skin tumor, in which
      one tumor component has light microscopic features of basal cell carcinoma,
      whereas the other has features of sarcoma. Clinical experience with this tumor is
      limited, and associated molecular genetic alterations are unknown. Herein, we
      report a unique case of metastatic basal cell carcinosarcoma, in which we
      analyzed the 2 components of the primary tumor as well as the metastasis by next
      generation sequencing. The patient was a 72-year-old man who presented with a 7
      year history of a large tumor of the left forearm. The tumor showed mixed
      features of basal cell carcinoma and undifferentiated sarcoma. The patient
      underwent a wide local excision and sentinel lymph node biopsy, which revealed
      microscopic subcapsular deposits of metastatic sarcomatoid tumor. One year later,
      intra-abdominal metastatic tumor was detected and resected. It had sarcomatoid
      features by light microscopy and failed to stain for epithelial markers by
      immunohistochemistry. DNA was extracted separately from the epithelial and
      sarcomatoid component of the primary tumor, intra-abdominal metastasis, and
      normal tissue. All exons of 230 cancer-associated genes were sequenced to an
      average read depth of >500-fold. This revealed multiple identical mutations in
      epithelial and sarcomatoid tumor compartments. Both compartments harbored 2
      identical mutations, a truncating and a missense mutation, in the patched gene
      (PTCH1). This finding is not only of interest for a shared heritage of different
      subpopulations in a biphenotypic tumor, but also relevant clinically. It provides
      a rationale for the clinical use of hedgehog pathway inhibitors for treatment of
      patients affected by this tumor. Unfortunately, the patient reported herein died
      of metastatic disease before targeted therapy could be initiated. 

PMID- 24335644
TI  - Possible neuroendocrine phenotype of poorly differentiated cell clusters in
      colorectal carcinoma, as a prognostic parameter.

PMID- 24335645
TI  - Practical utility and objectivity: does evaluation of peritoneal elastic laminal
      invasion in colorectal cancer overcome these contrary problems?

PMID- 24335646
TI  - Re: Practical utility and objectivity: does evaluation of peritoneal elastic
      laminal invasion in colorectal cancer overcome these contrary problems?

PMID- 24335647
TI  - Enrichment and purging of human embryonic stem cells by detection of cell surface
      antigens using the monoclonal antibodies TG30 and GCTM-2.
AB  - Human embryonic stem cells (hESC) can self-renew indefinitely in vitro, and with
      the appropriate cues can be induced to differentiate into potentially all somatic
      cell lineages. Differentiated hESC derivatives can potentially be used in
      transplantation therapies to treat a variety of cell-degenerative diseases.
      However, hESC differentiation protocols usually yield a mixture of differentiated
      target and off-target cell types as well as residual undifferentiated cells. For
      the translation of differentiated hESC-derivatives from the laboratory to the
      clinic, it is important to be able to discriminate between undifferentiated
      (pluripotent) and differentiated cells, and generate methods to separate these
      populations. Safe application of hESC-derived somatic cell types can only be
      accomplished with pluripotent stem cell-free populations, as residual hESCs could
      induce tumors known as teratomas following transplantation. Towards this end,
      here we describe a methodology to detect pluripotency associated cell surface
      antigens with the monoclonal antibodies TG30 (CD9) and GCTM-2 via fluorescence
      activated cell sorting (FACS) for the identification of pluripotent TG30(Hi)-GCTM
      2(Hi) hESCs using positive selection. Using negative selection with our TG30/GCTM
      2 FACS methodology, we were able to detect and purge undifferentiated hESCs in
      populations undergoing very early-stage differentiation (TG30(Neg)-GCTM-2(Neg)).
      In a further study, pluripotent stem cell-free samples of differentiated
      TG30(Neg)-GCTM-2(Neg) cells selected using our TG30/GCTM-2 FACS protocol did not
      form teratomas once transplanted into immune-compromised mice, supporting the
      robustness of our protocol. On the other hand, TG30/GCTM-2 FACS-mediated
      consecutive passaging of enriched pluripotent TG30(Hi)-GCTM-2(Hi) hESCs did not
      affect their ability to self-renew in vitro or their intrinsic pluripotency.
      Therefore, the characteristics of our TG30/GCTM-2 FACS methodology provide a
      sensitive assay to obtain highly enriched populations of hPSC as inputs for
      differentiation assays and to rid potentially tumorigenic (or residual) hESC from
      derivative cell populations. 

PMID- 24335648
TI  - Opportunities and challenges for an integrated, federal HIV services information
      system: implications for enhancing HIV programs.

PMID- 24335649
TI  - Calcium-dependent regulation of Rab activation and vesicle fusion by an
      intracellular P2X ion channel.
AB  - Rab GTPases play key roles in the delivery, docking and fusion of intracellular
      vesicles. However, the mechanism by which spatial and temporal regulation of Rab
      GTPase activity is controlled is poorly understood. Here we describe a mechanism
      by which localized calcium release through a vesicular ion channel controls Rab
      GTPase activity. We show that activation of P2XA, an intracellular ion channel
      localized to the Dictyostelium discoideum contractile vacuole system, results in
      calcium efflux required for downregulation of Rab11a activity and efficient
      vacuole fusion. Vacuole fusion and Rab11a downregulation require the activity of
      CnrF, an EF-hand-containing Rab GAP found in a complex with Rab11a and P2XA. CnrF
      Rab GAP activity for Rab11a is enhanced by the presence of calcium and the EF
      hand domain. These findings suggest that P2XA activation results in vacuolar
      calcium release, which triggers activation of CnrF Rab GAP activity and
      subsequent downregulation of Rab11a to allow vacuole fusion. 

PMID- 24335650
TI  - Stem cell quiescence acts as a tumour suppressor in squamous tumours.
AB  - In some organs, adult stem cells are uniquely poised to serve as cancer cells of
      origin. It is unclear, however, whether tumorigenesis is influenced by the
      activation state of the adult stem cell. Hair follicle stem cells (HFSCs) act as
      cancer cells of origin for cutaneous squamous cell carcinoma and undergo defined
      cycles of quiescence and activation. The data presented here show that HFSCs are
      unable to initiate tumours during the quiescent phase of the hair cycle,
      indicating that the mechanisms that keep HFSCs dormant are dominant over the gain
      of oncogenes (such as Ras) or the loss of tumour suppressors (such as p53).
      Furthermore, Pten activity is necessary for quiescence-based tumour suppression,
      as its deletion alleviates tumour suppression without affecting proliferation.
      These data demonstrate that stem cell quiescence is a form of tumour suppression
      in HFSCs, and that Pten plays a role in maintaining quiescence in the presence of
      tumorigenic stimuli. 

PMID- 24335651
TI  - Directing human embryonic stem cell differentiation towards a renal lineage
      generates a self-organizing kidney.
AB  - With the prevalence of end-stage renal disease rising 8% per annum globally,
      there is an urgent need for renal regenerative strategies. The kidney is a
      mesodermal organ that differentiates from the intermediate mesoderm (IM) through
      the formation of a ureteric bud (UB) and the interaction between this bud and the
      adjacent IM-derived metanephric mesenchyme (MM). The nephrons arise from a
      nephron progenitor population derived from the MM (ref. ). The IM itself is
      derived from the posterior primitive streak. Although the developmental origin of
      the kidney is well understood, nephron formation in the human kidney is completed
      before birth. Hence, there is no postnatal stem cell able to replace lost
      nephrons. In this study, we have successfully directed the differentiation of
      human embryonic stem cells (hESCs) through posterior primitive streak and IM
      under fully chemically defined monolayer culture conditions using growth factors
      used during normal embryogenesis. This differentiation protocol results in the
      synchronous induction of UB and MM that forms a self-organizing structure,
      including nephron formation, in vitro. Such hESC-derived components show broad
      renal potential ex vivo, illustrating the potential for pluripotent-stem-cell
      based renal regeneration. 

PMID- 24335654
TI  - Pharmacological therapies for acute respiratory distress syndrome.
AB  - PURPOSE OF REVIEW: Despite recent advances in the management of patients with
      acute respiratory distress syndrome (ARDS) by using protective ventilator
      strategies, the mortality rate of ARDS remains high. The complexity of the
      pathogenesis and the heterogeneity of coexisting diseases in patients with ARDS
      require critical care physicians and researchers to search for multiple
      therapeutic approaches in order to further improve patient outcome. This review
      article therefore focuses on the recent studies in the field of pharmacological
      intervention in ARDS. RECENT FINDINGS: A number of approaches for pharmacological
      intervention have been evaluated in patients with ARDS, but most of them failed
      to reduce mortality or improve outcomes despite some promising observations seen
      in preclinical studies. Prior methods such as nitric oxide inhalation,
      neuromuscular blocking agents and corticosteroids may still have a place in the
      treatment, while novel therapeutic approaches including the use of angiotensin
      converting enzyme inhibitors, statins and stem cells are currently under
      investigation. SUMMARY: Overall, there is no proven pharmacological therapy in
      ARDS, but some pharmacological interventions were associated with beneficial
      effects in certain subgroups of patients depending on the cause, underlying
      diseases, the concurrent supportive therapies and timing. Further clinical trials
      are warranted to assess multiple outcome measurement of the promising
      pharmacological interventions in selected patients with ARDS.

PMID- 24335655
TI  - Lung recruitment in acute respiratory distress syndrome: what is the best
      strategy?
AB  - PURPOSE OF REVIEW: Supporting patients with acute respiratory distress syndrome
      (ARDS) using a low tidal volume strategy is a standard practice in the ICU.
      Recruitment maneuvers can be used to augment other methods, like positive end
      expiratory pressure and positioning, to improve aerated lung volume. Clinical
      practice varies widely, and optimal method and patient selection for recruitment
      maneuvers have not been determined. RECENT FINDINGS: Recent developments include
      experimental and clinical evidence that a stepwise extended recruitment maneuver
      may match the improvement in aerated lung volume seen with sustained inflation
      traditionally used, with less adverse effects. Positioning and other chest wall
      modifications may be useful adjuncts to recruitment maneuvers. In addition,
      evidence from clinical studies in the operating room suggests that recruitment
      maneuvers, as a component of an open lung strategy, may be helpful for
      mechanically ventilated patients with normal lungs. SUMMARY: As a component of
      ventilation strategy for patients with ARDS, the use of recruitment maneuvers,
      especially a stepwise maneuver, in addition to adequate positive end-expiratory
      pressure and appropriate positioning, is suggested by currently available data.
      Until their effect on clinical outcomes is further defined, the use of
      recruitment maneuvers in ARDS and other settings will continue to be guided by
      individual clinician experience and patient factors.

PMID- 24335656
TI  - Spontaneous breathing in mild and moderate versus severe acute respiratory
      distress syndrome.
AB  - PURPOSE OF REVIEW: This review summarizes the most recent clinical and
      experimental data on the impact of spontaneous breathing in acute respiratory
      distress syndrome (ARDS). RECENT FINDINGS: Spontaneous breathing during assisted
      as well as nonassisted modes of mechanical ventilation improves lung function and
      reduces lung damage in mild and moderate ARDS. New modes of assisted mechanical
      ventilation with improved patient ventilator interaction and enhanced variability
      of the respiratory pattern offer additional benefit on lung function and damage.
      However, data supporting an outcome benefit of spontaneous breathing in ARDS,
      even in its mild and moderate forms, are missing. In contrast, controlled
      mechanical ventilation with muscle paralysis in the first 48 h of severe ARDS has
      been shown to improve survival, as compared with placebo. Currently, it is
      unclear whether ventilator settings, rather than the severity of lung injury,
      determine the potential of spontaneous breathing for benefit or harm. SUMMARY:
      Clinical and experimental studies show that controlled mechanical ventilation
      with muscle paralysis in the early phase of severe ARDS reduces lung injury and
      even mortality. At present, spontaneous breathing should be avoided in the early
      phase of severe ARDS, but considered in mild-to-moderate ARDS.

PMID- 24335657
TI  - To prevent or cure acute respiratory distress syndrome: that is the question!

PMID- 24335658
TI  - Against autonomy: justifying coercive paternalism.

PMID- 24335659
TI  - Prostitution and sexual ethics: a reply to Westin.

PMID- 24335661
TI  - Cervical conization and sentinel lymph node mapping in the treatment of stage I
      cervical cancer: is less enough?
AB  - OBJECTIVES: This study aimed to determine the feasibility of cervical conization
      and sentinel lymph node (SLN) mapping as a fertility-sparing strategy to treat
      stage I cervical cancer and to estimate the tumor margin status needed to achieve
      no residual carcinoma in the cervix. METHODS: We identified all patients who
      desired fertility preservation and underwent SLN mapping with cervical conization
      for stage I cervical cancer from September 2005 to August 2012. Relevant
      demographic, clinical, and pathologic information was collected. RESULTS: Ten
      patients were identified. Median age was 28 years (range, 18-36 years). None of
      the patients had a grossly visible tumor. The initial diagnosis of invasive
      carcinoma was made either on a loop electrosurgical excision procedure or cone
      biopsy. All patients underwent preoperative radiologic evaluation (magnetic
      resonance imaging and positron emission tomography-computed tomography). None of
      the patients had evidence of gross tumor or suspicion of lymph node metastasis on
      imaging. Stage distribution included 7 (70%) patients with stage IA1 cervical
      cancer with lymphovascular invasion and 3 (30%) patients with microscopic IB1.
      Histologic diagnosis included 8 (80%) patients with squamous cell carcinoma, 1
      (10%) patient with adenocarcinoma, and 1 (10%) patient with clear cell carcinoma.
      Nine patients underwent repeat cervical conization with SLN mapping, and 1
      patient underwent postconization cervical biopsies and SLN mapping. None of the
      patients had residual tumor identified on the final specimen. The median distance
      from the invasive carcinoma to the endocervical margin was 2.25 mm, and the
      distance from the invasive carcinoma to the ectocervical margin was 1.9 mm. All
      collected lymph nodes were negative for metastasis. After a median follow-up of
      17 months (range, 1-83 months), none of the patients' conditions were diagnosed
      with recurrent disease and 3 (30%) patients achieved pregnancy. CONCLUSIONS:
      Cervical conization and SLN mapping seems to be an acceptable treatment strategy
      for selected patients with small-volume stage I cervical cancer. Tumor clearance
      of 2 mm and above seems to correlate well with no residual on repeat conization.
      A larger sample size and longer follow-up is needed to establish the long-term
      outcomes of this procedure.

PMID- 24335662
TI  - Expression of estrogen receptor-alpha as a prognostic factor in patients with
      uterine serous carcinoma.
AB  - OBJECTIVES: Although the expression of estrogen receptor (ER) is usually found in
      uterine endometrioid adenocarcinomas, it has recently been reported to be found
      in some uterine serous carcinomas (USCs). This report describes the
      clinicopathologic features of USC with an expression of ER-alpha, with special
      reference to the prognostic significance of ER-alpha. METHODS: The
      immunohistochemical expression of ER-alpha was examined in 33 USCs. Greater than
      10% staining was defined as an overexpression of ER-alpha. Cox univariate and
      multivariate analyses for USCs were performed. RESULTS: A total of 7 USCs (21.2%)
      exhibited an expression of ER-alpha. All tumors were pure-type USCs and strongly
      demonstrated an overexpression of p53. The cancer-specific 5-year survival rates
      of patients with USC without an expression of ER-alpha and USC with an expression
      of ER-alpha were 54.5% and 0.0%, respectively (P = 0.04). The univariate analyses
      showed an expression of ER-alpha to be a significant prognostic indicator in
      patients with USC (P < 0.05). However, multivariate analyses for USCs showed that
      the surgical stage was an independent prognostic factor, whereas the significance
      of ER immunoreactivity disappeared. CONCLUSIONS: Uterine serous carcinoma with an
      expression of ER-alpha was associated with advanced-staged tumors and a
      significantly worse prognosis than that without an expression of ER-alpha. When
      an endometrial biopsy specimen reveals USC with an expression of ER-alpha and an
      overexpression of p53, the presence of an extrauterine lesion is suggested.

PMID- 24335663
TI  - Failure under stress: the effect of the exotic herbivore Adelges tsugae on
      biomechanics of Tsuga canadensis.
AB  - BACKGROUND AND AIMS: Exotic herbivores that lack a coevolutionary history with
      their host plants can benefit from poorly adapted host defences, potentially
      leading to rapid population growth of the herbivore and severe damage to its
      plant hosts. The hemlock woolly adelgid (Adelges tsugae) is an exotic hemipteran
      that feeds on the long-lived conifer eastern hemlock (Tsuga canadensis), causing
      rapid mortality of infested trees. While the mechanism of this mortality is
      unknown, evidence indicates that A. tsugae feeding causes a hypersensitive
      response and alters wood anatomy. This study investigated the effect of A. tsugae
      feeding on biomechanical properties at different spatial scales: needles, twigs
      and branches. METHODS: Uninfested and A. tsugae-infested samples were collected
      from a common garden experiment as well as from naturally infested urban and
      rural field sites. Tension and flexure mechanical tests were used to quantify
      biomechanical properties of the different tissues. In tissues that showed a
      significant effect of herbivory, the potential contributions of lignin and tissue
      density on the results were quantified. KEY RESULTS: Adelges tsugae infestation
      decreased the abscission strength, but not flexibility, of needles. A. tsugae
      feeding also decreased mechanical strength and flexibility in currently attacked
      twigs, but this effect disappeared in older, previously attacked branches. Lignin
      and twig tissue density contributed to differences in mechanical strength but
      were not affected by insect treatment. CONCLUSIONS: Decreased strength and
      flexibility in twigs, along with decreased needle strength, suggest that infested
      trees experience resource stress. Altered growth patterns and cell wall chemistry
      probably contribute to these mechanical effects. Consistent site effects
      emphasize the role of environmental variation in mechanical traits. The
      mechanical changes measured here may increase susceptibility to abiotic physical
      stressors in hemlocks colonized by A. tsugae. Thus, the interaction between
      herbivore and physical stresses is probably accelerating the decline of eastern
      hemlock, as HWA continues to expand its range.

PMID- 24335664
TI  - Pregnancy luteoma: a study of 20 cases on the occasion of the 50th anniversary of
      its description by Dr. William H. Sternberg, with an emphasis on the common
      presence of follicle-like spaces and their diagnostic implications.
AB  - Twenty cases of the distinctive tumor-like lesion of the ovary, pregnancy
      luteoma, are described, with emphasis on pathologic features. The masses occurred
      in patients from 15 to 44 years of age and were typically incidental findings at
      or near term. Four patients experienced androgenic manifestations. The luteoma
      was documented to be bilateral in only 4 cases, but the opposite ovary was
      usually not evaluated pathologically. They ranged up to 15 cm. Sectioning
      typically showed multiple nodules or a single discrete mass with a multinodular
      sectioned surface and a soft bulging appearance. Most lesions were brown, but a
      few were black or yellow at least focally. Foci of hemorrhage were common. The
      most common microscopic appearance was a diffuse growth, but it was punctuated in
      about three quarters of the cases by follicle-like spaces often containing
      colloid-like secretion. These spaces are much more characteristic of the
      pregnancy luteoma than of the lesion most often in the differential diagnosis, a
      steroid cell tumor, and accordingly may be of diagnostic aid. However, they may
      cause confusion, as follicle-like spaces are a nonspecific feature of a number of
      neoplasms involving the ovary and potentially in the differential diagnosis.
      Awareness of the clinical background and frequency of finding follicle-like
      spaces in pregnancy luteoma are important diagnostically, and standard
      immunohistochemical stains will aid should they be warranted. 

PMID- 24335665
TI  - Intrapatient homogeneity of BRAFV600E expression in melanoma.
AB  - Concern regarding the presence of intertumoral heterogeneity of BRAF mutation
      status in patients with metastatic melanoma has led to uncertainty surrounding
      which specimens should preferentially undergo BRAF testing. We sought to examine
      the extent of intrapatient heterogeneity of BRAF(V600E) protein expression in
      patients with multiple tumors. Sixty-four patients with 171 tumors at various
      stages of disease progression had tumor BRAF(V600E) protein expression
      immunohistochemically (IHC) assessed using the BRAF(V600E) mutant-specific
      antibody VE1. Melanoma sections were examined for staining intensity (score 0 to
      3), the presence of intratumoral heterogeneity, and concordance with molecular
      BRAF genotype. Intrapatient, intertumoral heterogeneity of BRAF(V600E) expression
      was also assessed by comparing VE1 staining on different tumors within the same
      patient. All specimens from 64 patients displayed complete intertumoral
      homogeneity of BRAF(V600E) expression status, and all tumors had concordant
      molecular and IHC BRAF status. Only 1 patient demonstrated >1 level of staining
      intensity heterogeneity between specimens. Intratumoral heterogeneity of staining
      intensity was not observed in any specimen. IHC-measured BRAF(V600E) protein
      expression displays complete intertumoral homogeneity, minimal intertumoral
      intensity heterogeneity, and no intratumoral heterogeneity in metastatic melanoma
      patients in various stages of disease progression. Our results suggest that,
      provided there is adequate quantity of viable tumor cells and minimal admixture
      of nontumor cells, testing any melanoma sample from a patient with metastatic
      disease will accurately determine BRAF status for treatment planning.

PMID- 24335666
TI  - Rubus idaeus L Inhibits Invasion Potential of Human A549 Lung Cancer Cells by
      Suppression Epithelial-to-Mesenchymal Transition and Akt Pathway In Vitro and
      Reduces Tumor Growth In Vivo.
AB  - The metastasis of lung cancer is the most prevalent cause of patient death.
      Various treatment strategies have targeted the prevention of the occurrence of
      metastasis. The epithelial-mesenchymal transition (EMT) in lung cancer cells is
      considered a prerequisite to acquire the invasive/migratory phenotype and to
      subsequently achieve metastasis. However, the effects ofRubus idaeuson cancer
      invasion and the EMT of the human lung carcinoma remain unclear. In this article,
      we test the hypothesis thatR idaeusethyl acetate (RIAE) possesses an
      antimetastatic effect and reverses the EMT potential of human lung A549 cells. We
      extract the raspberryR idaeuswith methanol (RIME), chloroform (RICE), ethyl
      acetate (RIAE),n-butanol (RIBE), and water (RIWE). The RIAE treatment obviously
      inhibits the invasive (P< .001), motility (P< .001), spreading, and migratory
      potential (P< .001) of highly metastatic human lung cancer A549 cells. The
      zymography and promoter luciferase analysis reveals that RIAE decreases the
      proteinase and transcription activities of MMP-2 and u-PA. Molecular analyses
      show that RIAE increases the E-cadherin level that is mainly localized at the
      cellular membrane. This result was also verified through confocal analyses. RIAE
      also induces the upregulation of an epithelial marker, such as alpha-catenin, and
      decreases mesenchymal markers, such as snail-1 and N-cadherin, that promote cell
      invasion and metastasis. RIAE inhibits MMP-2 and u-PA by attenuating the NF
      kappaB and p-Akt expression. The inhibition of RIAE on the growth of A549 cells
      in vivo was also verified using a cancer cell xenograft nude mice model. Our
      results show the anti-invasive/antitumor effects of RIAE and associated
      mechanisms, which suggest that RIAE should be further tested in clinically
      relevant models to exploit its potential benefits against metastatic lung cancer
      cells. 

PMID- 24335667
TI  - Tied up in science: unknotting an old anaesthetic problem.

PMID- 24335670
TI  - A unified model of patient safety (or "Who froze my cheese?").

PMID- 24335668
TI  - Duration of symptoms of respiratory tract infections in children: systematic
      review.
AB  - OBJECTIVE: To determine the expected duration of symptoms of common respiratory
      tract infections in children in primary and emergency care. DESIGN: Systematic
      review of existing literature to determine durations of symptoms of earache, sore
      throat, cough (including acute cough, bronchiolitis, and croup), and common cold
      in children. DATA SOURCES: PubMed, DARE, and CINAHL (all to July 2012).
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials or
      observational studies of children with acute respiratory tract infections in
      primary care or emergency settings in high income countries who received either a
      control treatment or a placebo or over-the-counter treatment. Study quality was
      assessed with the Cochrane risk of bias framework for randomised controlled
      trials, and the critical appraisal skills programme framework for observational
      studies. MAIN OUTCOME MEASURES: Individual study data and, when possible, pooled
      daily mean proportions and 95% confidence intervals for symptom duration. Symptom
      duration (in days) at which each symptom had resolved in 50% and 90% of children.
      RESULTS: Of 22,182 identified references, 23 trials and 25 observational studies
      met inclusion criteria. Study populations varied in age and duration of symptoms
      before study onset. In 90% of children, earache was resolved by seven to eight
      days, sore throat between two and seven days, croup by two days, bronchiolitis by
      21 days, acute cough by 25 days, common cold by 15 days, and non-specific
      respiratory tract infections symptoms by 16 days. CONCLUSIONS: The durations of
      earache and common colds are considerably longer than current guidance given to
      parents in the United Kingdom and the United States; for other symptoms such as
      sore throat, acute cough, bronchiolitis, and croup the current guidance is
      consistent with our findings. Updating current guidelines with new evidence will
      help support parents and clinicians in evidence based decision making for
      children with respiratory tract infections.

PMID- 24335669
TI  - Red flags to screen for malignancy and fracture in patients with low back pain:
      systematic review.
AB  - OBJECTIVE: To review the evidence on diagnostic accuracy of red flag signs and
      symptoms to screen for fracture or malignancy in patients presenting with low
      back pain to primary, secondary, or tertiary care. DESIGN: Systematic review.
      DATA SOURCES: Medline, OldMedline, Embase, and CINAHL from earliest available up
      to 1 October 2013. INCLUSION CRITERIA: Primary diagnostic studies comparing red
      flags for fracture or malignancy to an acceptable reference standard, published
      in any language. REVIEW METHODS: Assessment of study quality and extraction of
      data was conducted by three independent assessors. Diagnostic accuracy statistics
      and post-test probabilities were generated for each red flag. RESULTS: We
      included 14 studies (eight from primary care, two from secondary care, four from
      tertiary care) evaluating 53 red flags; only five studies evaluated combinations
      of red flags. Pooling of data was not possible because of index test
      heterogeneity. Many red flags in current guidelines provide virtually no change
      in probability of fracture or malignancy or have untested diagnostic accuracy.
      The red flags with the highest post-test probability for detection of fracture
      were older age (9%, 95% confidence interval 3% to 25%), prolonged use of
      corticosteroid drugs (33%, 10% to 67%), severe trauma (11%, 8% to 16%), and
      presence of a contusion or abrasion (62%, 49% to 74%). Probability of spinal
      fracture was higher when multiple red flags were present (90%, 34% to 99%). The
      red flag with the highest post-test probability for detection of spinal
      malignancy was history of malignancy (33%, 22% to 46%). CONCLUSIONS: While
      several red flags are endorsed in guidelines to screen for fracture or
      malignancy, only a small subset of these have evidence that they are indeed
      informative. These findings suggest a need for revision of many current
      guidelines.

PMID- 24335671
TI  - Welcome to the most exclusive club in the NHS.

PMID- 24335672
TI  - Parveen Kumar: Pet hate is arrogance.

PMID- 24335674
TI  - Globotriaosylceramide induces endothelial dysfunction in fabry disease.

PMID- 24335675
TI  - Peroxisome proliferator activated receptor-delta: the middle child vies for
      attention.

PMID- 24335678
TI  - Colon cancer screening continues as pivotal to cancer prevention.

PMID- 24335677
TI  - Rapid generation of amyloid from native proteins in vitro.
AB  - Proteins carry out crucial tasks in organisms by exerting functions elicited from
      their specific three dimensional folds. Although the native structures of
      polypeptides fulfill many purposes, it is now recognized that most proteins can
      adopt an alternative assembly of beta-sheet rich amyloid. Insoluble amyloid
      fibrils are initially associated with multiple human ailments, but they are
      increasingly shown as functional players participating in various important
      cellular processes. In addition, amyloid deposited in patient tissues contains
      nonproteinaceous components, such as nucleic acids and glycosaminoglycans (GAGs).
      These cofactors can facilitate the formation of amyloid, resulting in the
      generation of different types of insoluble precipitates. By taking advantage of
      our understanding how proteins misfold via an intermediate stage of soluble
      amyloid precursor, we have devised a method to convert native proteins to amyloid
      fibrils in vitro. This approach allows one to prepare amyloid in large
      quantities, examine the properties of amyloid generated from specific proteins,
      and evaluate the structural changes accompanying the conversion. 

PMID- 24335680
TI  - A case of unusual mast cell response with interstitial cystitis-like symptoms to
      neoadjuvant chemotherapy for muscle-invasive transitional cell carcinoma of the
      bladder.
AB  - Randomized trials support the use of neoadjuvant chemotherapy in muscle-invasive
      bladder cancer based on a noted survival advantage, which appeared to be strongly
      related to downstaging of the cancer to pT0 (complete pathologic response). This
      report presents a case of an unusual mast cell response along with bladder wall
      thickening after neoadjuvant chemotherapy. However, the final cystectomy specimen
      did not reveal any residual tumor (pT0). The authors hypothesize that neoadjuvant
      chemotherapy could have caused the diffuse mast cell response, and that this
      profound inflammatory response can be used as a biomarker of complete response to
      chemotherapy.

PMID- 24335681
TI  - Vemurafenib treatment of BRAF V600E-mutated malignant peripheral nerve sheath
      tumor.
AB  - No effective systemic treatment exists for malignant peripheral nerve sheath
      tumors (MPNSTs). These tumors have been reported to show increased activity in
      the mitogen-activated protein kinase pathway from the loss of neurofibromatosis-1
      regulation and occasionally from BRAF V600E mutation. A patient with sporadic
      metastatic MPNST and the BRAF V600E mutation was treated with standard doses of
      sorafenib and later vemurafenib and followed for response. The patient showed a
      rapid but modest and transient response to sorafenib and a very dramatic response
      to vemurafenib. This case represents the first report of successful systemic
      treatment of MPNST with an inhibitor of the BRAF V600E mutation. It will be
      important to define the general utility of this approach and related therapies in
      this disease.

PMID- 24335683
TI  - Measuring quality in oncology: challenges and opportunities.
AB  - Variations in the quality of cancer care are well documented. A key element of
      quality monitoring is standardized measures of care. Quality measures may include
      both process measures and outcome measures. Process measurement is only one
      aspect of assessing the quality of cancer care; measuring outcomes and providing
      the appropriate structure for care are also important. A variety of stakeholders,
      including professional oncology organizations and public and private payors, have
      developed programs and quality measures to address variations in the delivery of
      cancer care. To fulfill the current need to explore and discuss how quality is
      measured in oncology care, NCCN convened the NCCN Oncology Policy Summit:
      Measuring Quality in Oncology - Challenges and Opportunities. The summit was a
      forum to discuss current efforts to use quality measures, the value of quality
      measures, and patient and caretaker perspectives on quality.

PMID- 24335682
TI  - Prostate cancer, version 1.2014.
AB  - The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations
      on the clinical management of patients with prostate cancer. This report
      highlights notable recent updates. Radium-223 dichloride is a first-in-class
      radiopharmaceutical that recently received approval for the treatment of patients
      with symptomatic bone metastases and no known visceral disease. It received a
      category 1 recommendation as both a first-line and second-line option. The NCCN
      Prostate Cancer Panel also revised recommendations on the choice of intermittent
      or continuous androgen deprivation therapy based on recent phase III clinical
      data comparing the 2 strategies in the nonmetastatic and metastatic settings.

PMID- 24335684
TI  - Determining chemotherapy tolerance in older patients with cancer.
AB  - Older adults with cancer constitute a heterogeneous group of patients who pose
      unique challenges for oncology care. One major concern is how to identify
      patients who are at a higher risk for chemotherapy intolerance, because a
      standard oncology workup may not always be able to distinguish an older
      individual's level of risk for treatment-related complications. Geriatric
      oncologists incorporate tools used in the field of geriatrics, and have developed
      the Comprehensive Geriatric Assessment to enhance the standard oncology workup.
      This assessment pinpoints problems with daily activities, comorbidities,
      medications, nutritional status, cognitive function, psychological state, and
      social support systems, all of which are risk factors for treatment vulnerability
      in older adults with cancer. Additional tools that also serve to predict
      chemotherapy toxicity in older patients with cancer are now available to identify
      patients at higher risk for morbidity and mortality. Together, these instruments
      complement the standard oncology workup by providing a global assessment, thereby
      guiding therapeutic interventions that may improve a patient's quality of life
      and clinical outcomes.

PMID- 24335685
TI  - Oncofertility resources at NCI-designated comprehensive cancer centers.
AB  - NCI-designated comprehensive cancer centers (CCCs) set the standard for providing
      exemplary patient care. Quality cancer care includes discussions about fertility
      and referrals to fertility specialists for patients at risk for sterility. This
      study sought to determine what fertility preservation (FP) resources are
      available in CCCs and how well those are integrated into patient care. Leaders at
      each CCC received a letter requesting a short telephone interview with
      individuals who could provide information about the institution's FP resources. A
      semi-structured interview guide was used and responses were audio-recorded. Data
      were analyzed using content and thematic analysis. Interviews were conducted with
      30 of the 39 CCCs that see adult patients (77%). The remaining institutions
      included 4 nonresponders, 3 that referred the interviewers to childhood cancer
      survivorship clinics, 1 that refused, and 1 that could not identify any FP
      resources. Participants were primarily affiliated with reproductive endocrinology
      (n=15) or hematology/oncology divisions (n=10). Institutional policies regarding
      consistent provision of FP information were rare (n=4), although most sites
      (n=20) either had some services on-site or had referral programs (n=8). However,
      only 13 had some experimental services, such as ovarian tissue cryopreservation.
      Respondents reported barriers to provision of FP, including oncologists'
      identification of patients at risk, low referral rates, and perceptions of
      patient prognosis. Only 8 (27%) sites had staff with time dedicated to FP. CCCs
      vary widely in implementing FP-recommended practice to their patients. CCCs are
      positioned to provide exemplary oncofertility care, but most need to better
      integrate FP information and referral into practice.

PMID- 24335686
TI  - Postconsolidation maintenance and monitoring in patients with acute promyelocytic
      leukemia.
AB  - Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia
      (AML). Its exclusivity is reflected by both the clinical course and the
      management of patients. This article discusses 2 aspects of the unique management
      of patients with APL: the role of maintenance therapy and polymerase chain
      reaction (PCR) monitoring. Despite common practice, the efficacy of maintenance
      therapy in APL is still debated, and the introduction of arsenic trioxide into
      frontline protocols makes this debate even more challenging. This article also
      attempts to clarify details regarding the type and duration of maintenance
      treatment. The presence of residual leukemic cells, seen using PCR analysis of
      the PML/RARalpha fusion gene product, in patients who have experienced a complete
      response has been shown to have a high correlation with subsequent relapse. This
      fact led to the broad use of PCR monitoring techniques in patients with APL.
      Practicing clinicians face several questions with regard to monitoring, such as
      what is the best technique for monitoring patients with APL, who can benefit the
      most from these tests, what are the best time points, and for how long is
      monitoring recommended. These questions are addressed in this article.

PMID- 24335687
TI  - Sleep disruption in breast cancer patients and survivors.
AB  - Sleep disruption is prevalent in patients and survivors of breast cancer. Most
      patients undergoing chemotherapy will experience transient sleep disruption, and
      nearly 60% will have chronic sleep problems. Numerous factors contribute to sleep
      disruption in women diagnosed with breast cancer. Sleep disruption is a
      consequence of several biological alterations, including circadian disruption and
      immune and metabolic deregulations. These systems also play significant roles in
      the control and progression of breast cancer. Sleep disruption is associated with
      many side effects and psychiatric and medical comorbidities. This article
      discusses the relationship between stress and posttraumatic stress disorder,
      depression and fatigue, and how sleep disturbance might be the cause or
      consequence of these disorders. Current evidence for management of sleep
      disturbance in breast cancer and high chronic use of hypnotic medication in this
      population is also discussed. Finally, the differences in management of sleep
      disturbance during acute cancer care and during the survivorship phase are
      discussed. More research is needed on accurate and timely assessment of sleep
      disturbance associated with breast cancer, and additional tailored approaches for
      the management of sleep problems in breast cancer should be developed.

PMID- 24335688
TI  - Colorectal cancer screening.
AB  - Mortality from colorectal cancer can be reduced by early diagnosis and by cancer
      prevention through polypectomy. These NCCN Guidelines for Colorectal Cancer
      Screening describe various colorectal screening modalities and recommended
      screening schedules for patients at average or increased risk of developing
      colorectal cancer. In addition, the guidelines provide recommendations for the
      management of patients with high-risk colorectal cancer syndromes, including
      Lynch syndrome. Screening approaches for Lynch syndrome are also described.

PMID- 24335689
TI  - When and how to perform genetic testing for inherited colorectal cancer
      syndromes.
AB  - The 2013 NCCN Clinical Practice Guidelines in Oncology for Colorectal Cancer
      Screening address the evaluation and management of patients at risk of inherited
      susceptibility to colorectal cancer. These patients include the 2 broad
      categories of patients with familial adenomatous polyposis and its variants, and
      those with hereditary nonpolyposis colorectal cancer, or Lynch syndrome. This
      article provides a somewhat personal, yet hopefully evidence-based, approach to
      the questions of when to test individuals for inherited susceptibility, and how
      to do so. "When" can be taken to mean "under what circumstance" and "at what
      age"; this article attempts to speak to each sense of the term.

PMID- 24335690
TI  - Sessile serrated polyps: an important route to colorectal cancer.
AB  - The serrated neoplastic pathway accounts for approximately 30% of colorectal
      cancers. Characterized by mutations in the oncogene BRAF, DNA promoter
      hypermethylation, and microsatellite instability, cancers arising in this pathway
      develop via serrated polyp intermediates. Serrated polyps represent a
      heterogeneous group of lesions with distinct genetic, molecular, and clinical
      features. Sessile serrated polyps (also called sessile serrated adenomas) have
      emerged as the key intermediates in this pathway. These lesions have malignant
      potential and are often difficult to detect endoscopically, thus contributing to
      the development of interval cancers. Recent advances in the understanding of
      sessile serrated polyps have led to new histologic classifications, increased
      endoscopic recognition, and changes in clinical management recommendations. This
      article focuses on sessile serrated polyps as a unique and important route to
      colorectal cancer.

PMID- 24335691
TI  - Caring for the whole patient.

PMID- 24335695
TI  - Benefit from prolonged dose-intensive chemotherapy for infants with malignant
      brain tumors is restricted to patients with ependymoma: a report of the Pediatric
      Oncology Group randomized controlled trial 9233/34.
AB  - BACKGROUND: The randomized controlled Pediatric Oncology Group study 9233 tested
      the hypothesis that dose-intensive (DI) chemotherapy would improve event-free
      survival (EFS) for children <3 years of age with newly diagnosed malignant brain
      tumors. METHODS: Of 328 enrolled eligible patients, diagnoses were
      medulloblastoma (n = 112), ependymoma (n = 82), supratentorial primitive
      neuroectodermal tumor (sPNET, n = 38) and other malignant brain tumors (n = 96),
      and were randomized to 72 weeks of standard dose chemotherapy (Regimen A, n =
      162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was
      recommended for patients with evidence of disease at completion of chemotherapy
      or who relapsed within 6 months of chemotherapy completion. RESULTS:
      Distributions of EFS for Regimens A and B were not significantly different (P =
      0.32) with 2- and 10-year rates of 22.8% +/- 3.3% and 15.4% +/- 3.7%, and 27.1%
      +/- 3.4% and 20.8% +/- 3.8%, respectively. Thus, the study hypothesis was
      rejected. While distributions of EFS and OS were not significantly different
      between Regimens A and B for patients with medulloblastoma and sPNET, DI
      chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2
      year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution,
      for patients with centrally confirmed ependymoma. The degree of surgical
      resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40%
      and 20% of patients with medulloblastoma, ependymoma treated with DI
      chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11
      toxic deaths on study, 10 occurred on the DI chemotherapy arm. CONCLUSIONS:
      Prolonged dose-intensive chemotherapy given to infants with malignant brain
      tumors resulted in increased EFS only for patients with ependymoma.

PMID- 24335696
TI  - NCoR controls glioblastoma tumor cell characteristics.
AB  - BACKGROUND: We have previously shown that the transcriptional coregulator NCoR
      represses astrocytic differentiation of neural stem cells, suggesting that NCoR
      could be a plausible target for differentiation therapy of glioblastoma. METHODS:
      To study a putative role for NCoR in regulating glioblastoma cell
      characteristics, we used RNA-mediated knockdown followed by analysis of gene
      expression, proliferation and cell growth, autophagy, invasiveness in vitro, and
      tumor formation in vitro and in vivo. We further performed chromatin
      immunoprecipitation of NCoR followed by genome-wide sequencing in the human
      glioblastoma cell line U87 in order to reveal NCoR-occupied loci. RESULTS: RNA
      knockdown of NCoR resulted in a moderate increase in differentiation accompanied
      by a significant decrease in proliferation in adherent U87 human glioblastoma
      cells. chromatin immunoprecipitation sequencing approach revealed alternative
      mechanisms underlying the decrease in proliferation, as NCoR was enriched at
      promoters of genes associated with autophagy such as ULK3. Indeed, signs of an
      autophagy response in adherent glioblastoma cells included an increased
      expression of autophagy genes, such as Beclin1, and increased lipidation and
      nuclear puncta of LC3. Intriguingly, in parallel to the effects in the adherent
      cells, NCoR knockdown resulted in a significant increase in anchorage-independent
      growth, and this glioblastoma cell population showed dramatic increases in
      invasive properties in vitro and tumor formation capacity in vitro and in vivo
      along with an increased proliferation rate. CONCLUSION: Our results unveil
      unexpected aspects of NCoR regulation of tumor characteristics in glioblastoma
      cells and highlight the need for caution when transposing developmental concepts
      directly to cancer therapy.

PMID- 24335697
TI  - Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas.
AB  - BACKGROUND: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of
      gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have
      been shown to be closely associated with oligodendroglial phenotype and better
      prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted
      LGGs. METHODS: We characterized a retrospective series of 126 LGGs using genomic
      arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay,
      and p53 expression analysis. RESULTS: Our study confirms that 1p/19q codeletion,
      mutually exclusive with p53 overexpression, was associated with: (i) better
      prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and
      (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients
      at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5
      main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain,
      and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p
      loss is associated with astrocytoma phenotype and has an independent negative
      prognostic value, and (ii) 19q loss diminished the favorable prognostic value of
      IDH mutation. Our findings were validated in an independent cohort of 98 LGGs.
      CONCLUSION: Novel genomic entities and biomarkers have been identified in non
      1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted
      LGGs, facilitating future individualization of treatment. Further prospective
      studies are warranted to support our findings.

PMID- 24335698
TI  - Brain tumor cell line authentication, an efficient alternative to capillary
      electrophoresis by using a microfluidics-based system.
AB  - BACKGROUND: The current method for cell line authentication is genotyping based
      on short tandem repeat (STR)-PCR involving coamplification of a panel of STR loci
      by multiplex PCR and downstream fragment length analysis (FLA), usually performed
      by capillary electrophoresis. FLA by capillary electrophoresis is time-consuming
      and can be expensive, as the facilities are generally not accessible for many
      research laboratories. METHODS: In the present study, a microfluidic
      electrophoresis system, the Agilent 2100 Bioanalyzer, was used to analyze the STR
      PCR fragments from 10 human genomic loci of a number of human cell lines,
      including 6 gliomas, 1 astrocyte, 1 primary lung cancer, 1 lung brain metastatic
      cancer, and 1 rhabdomyosarcoma; and this was compared with the standard method,
      that is, capillary electrophoresis, using the Applied Biosystems 3130xl Genetic
      Analyzer. RESULTS: The microfluidic electrophoresis method produced highly
      reproducible results with good sensitivity in sizing of multiple PCR fragments,
      and each cell line demonstrated a unique DNA profile. Furthermore, DNA
      fingerprinting of samples from 5 different passage numbers of the same cell line
      showed excellent reproducibility when FLA was performed with the Bioanalyzer,
      indicating that no cross-contamination had occurred during the culture period.
      CONCLUSION: This novel application provides a straightforward and cost-effective
      alternative to STR-based cell line authentication. In addition, this application
      would be of great value for cell bank repositories to maintain and distribute
      precious cell lines.

PMID- 24335701
TI  - The long-term outcomes of radiosurgery for intracranial hemangioblastomas.
AB  - BACKGROUND: Optimal timing in the treatment of intracranial hemangioblastoma (HB)
      remains controversial, particularly for patients of von Hippel-Lindau disease
      (VHL) with multiple small lesions. We evaluated efficacy of stereotactic
      radiosurgery (SRS) for intracranial HB based on the longer follow-up data with a
      larger number of patients and lesions. METHODS: Twenty-one patients (11 men, 10
      women) initially underwent SRS for 57 intracranial HBs. Seven patients had
      sporadic lesions and 14 had VHL-related lesions. During the follow-up, 40 lesions
      were additionally treated in VHL patients in 10 SRS treatments. Thus, a total of
      97 lesions were included in this study. Median tumor volume was 0.13 cm(3)
      (range, 0.004-9.5 cm(3)), and median margin dose was 18 Gy (range, 14-20 Gy).
      RESULTS: Median duration of follow-up was 96 months (range, 3-235 mo) after
      initial SRS treatment. Ten tumors in 7 patients showed progression after SRS.
      Actuarial tumor control rates after SRS at 5 and 10 years were 94% and 80%,
      respectively. Factors associated with longer control were solid lesion (P = .03),
      smaller volume (P = .01), and lesions associated with VHL (P = .0005) in
      univariate analysis. Five- and 10-year tumor control rates were 67% and 44% for
      sporadic patients and 97% and 83% for VHL patients. CONCLUSION: SRS could be
      offered as an effective treatment for small, solid, and VHL-associated HBs. If
      the tumors show apparent enlargement in size or can possibly become symptomatic
      along with a slight increase in size, SRS should be recommended before they
      present with the clinical symptoms.

PMID- 24335700
TI  - Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a
      phase II, single-arm trial.
AB  - BACKGROUND: Outcomes for patients with recurrent glioblastoma multiforme (GBM)
      are poor and may be improved by immunotherapy. We investigated the safety and
      efficacy of an autologous heat-shock protein peptide complex-96 (HSPPC-96)
      vaccine for patients with recurrent GBM. METHODS: In this open-label, single-arm,
      phase II study, adult patients with surgically resectable recurrent GBM were
      given vaccine after gross total resection. The primary endpoint was overall
      survival at 6 months. Secondary endpoints included overall survival, progression
      free survival, safety, and immune profiling. Outcome analyses were performed in
      the intention-to-treat and efficacy populations. RESULTS: Between October 3, 2007
      and October 24, 2011, 41 patients underwent gross total resection of recurrent
      GBM and received a median of 6 doses of HSPPC-96 vaccine. Following treatment,
      90.2% of patients were alive at 6 months (95% confidence interval [CI]: 75.9
      96.8) and 29.3% were alive at 12 months (95% CI: 16.6-45.7). Median overall
      survival was 42.6 weeks (95% CI: 34.7-50.5). Twenty-seven (66%) patients were
      lymphopenic prior to therapy, and patients with lymphocyte counts below the
      cohort median demonstrated decreased overall survival (hazard ratio: 4.0; 95% CI:
      1.4-11.8; P = .012). There were no treatment-related deaths. There were 37
      serious (grades 3-5) adverse events reported, with 17 attributable to surgical
      resection and a single grade 3 constitutional event related to the vaccine.
      CONCLUSION: The HSPPC-96 vaccine is safe and warrants further study of efficacy
      for the treatment of recurrent GBM. Significant pretreatment lymphopenia may
      impact the outcomes of immunotherapy and deserves additional investigation.

PMID- 24335699
TI  - Progression-free survival as a surrogate endpoint for overall survival in
      glioblastoma: a literature-based meta-analysis from 91 trials.
AB  - BACKGROUND: The aim of this study was to determine correlations between
      progression-free survival (PFS) and the objective response rate (ORR) with
      overall survival (OS) in glioblastoma and to evaluate their potential use as
      surrogates for OS. METHOD: Published glioblastoma trials reporting OS and ORR
      and/or PFS with sufficient detail were included in correlative analyses using
      weighted linear regression. RESULTS: Of 274 published unique glioblastoma trials,
      91 were included. PFS and OS hazard ratios were strongly correlated; R(2) = 0.92
      (95% confidence interval [CI], 0.71-0.99). Linear regression determined that a
      10% PFS risk reduction would yield an 8.1% +/- 0.8% OS risk reduction. R(2)
      between median PFS and median OS was 0.70 (95% CI, 0.59-0.79), with a higher
      value in trials using Response Assessment in Neuro-Oncology (RANO; R(2) = 0.96, n
      = 8) versus Macdonald criteria (R(2) = 0.70; n = 83). No significant differences
      were demonstrated between temozolomide- and bevacizumab-containing regimens (P =
      .10) or between trials using RANO and Macdonald criteria (P = .49). The
      regression line slope between median PFS and OS was significantly higher in newly
      diagnosed versus recurrent disease (0.58 vs 0.35, P = .04). R(2) for 6-month PFS
      with 1-year OS and median OS were 0.60 (95% CI, 0.37-0.77) and 0.64 (95% CI, 0.42
      0.77), respectively. Objective response rate and OS were poorly correlated (R(2)
      = 0.22). CONCLUSION: In glioblastoma, PFS and OS are strongly correlated,
      indicating that PFS may be an appropriate surrogate for OS. Compared with OS, PFS
      offers earlier assessment and higher statistical power at the time of analysis.

PMID- 24335702
TI  - Reaction-based fluorescent sensor for investigating mobile Zn2+ in mitochondria
      of healthy versus cancerous prostate cells.
AB  - Chelatable, mobile forms of divalent zinc, Zn(II), play essential signaling roles
      in mammalian biology. A complex network of zinc import and transport proteins has
      evolved to control zinc concentration and distribution on a subcellular level.
      Understanding the action of mobile zinc requires tools that can detect changes in
      Zn(II) concentrations at discrete cellular locales. We present here a zinc
      responsive, reaction-based, targetable probe based on the diacetyled form of
      Zinpyr-1. The compound, (6-amidoethyl)triphenylphosphonium Zinpyr-1 diacetate (DA
      ZP1-TPP), is essentially nonfluorescent in the metal-free state; however,
      exposure to Zn(II) triggers metal-mediated hydrolysis of the acetyl groups to
      afford a large, rapid, and zinc-induced fluorescence response. DA-ZP1-TPP is
      insensitive to intracellular esterases over a 2-h period and is impervious to
      proton-induced turn-on. A TPP unit is appended for targeting mitochondria, as
      demonstrated by live cell fluorescence imaging studies. The practical utility of
      DA-ZP1-TPP is demonstrated by experiments revealing that, in contrast to healthy
      epithelial prostate cells, tumorigenic cells are unable to accumulate mobile zinc
      within their mitochondria. 

PMID- 24335703
TI  - Profile of Peter Novick.

PMID- 24335704
TI  - Human herpesvirus 6 (HHV-6) alters E2F1/Rb pathways and utilizes the E2F1
      transcription factor to express viral genes.
AB  - E2F transcription factors play pivotal roles in controlling the expression of
      genes involved in cell-cycle progression. Different viruses affect
      E2F1/retinoblastoma (Rb) interactions by diverse mechanisms releasing E2F1 from
      its suppressor Rb, enabling viral replication. We show that in T cells infected
      with human herpesvirus 6A (HHV-6A), the E2F1 protein and its cofactor DP1
      increased, whereas the Rb protein underwent massive degradation without
      hyperphosphorylation at three sites known to control E2F/Rb association. Although
      E2F1 and DP1 increased without Rb suppression, the E2F1 target genes-including
      cyclin A, cyclin E, and dihydrofolate reductase-were not up-regulated. To test
      whether the E2F1/DP1 complexes were used for viral transcription, we scanned the
      viral genome for genes containing the E2F binding site in their promoters. In the
      present work, we concentrated on the U27 and U79 genes known to act in viral DNA
      synthesis. We constructed amplicon-6 vectors containing a GFP reporter gene
      driven by WT viral promoter or by promoter mutated in the E2F binding site. We
      found that the expression of the fusion U27 promoter was dependent on the
      presence of the E2F binding site. Test of the WT U79 promoter yielded >10-fold
      higher expression of the GFP reporter gene than the mutant U79 promoter with
      abrogated E2F binding site. Moreover, by using siRNA to E2F1, we found that E2F1
      was essential for the activity of the U79 promoter. These findings revealed a
      unique pathway in HHV-6 replication: The virus causes Rb degradation and uses the
      increased E2F1 and DP1 factors to transcribe viral genes. 

PMID- 24335705
TI  - Morphological optimization for access to dual oxidants in biofilms.
AB  - A major theme driving research in biology is the relationship between form and
      function. In particular, a longstanding goal has been to understand how the
      evolution of multicellularity conferred fitness advantages. Here we show that
      biofilms of the bacterium Pseudomonas aeruginosa produce structures that maximize
      cellular reproduction. Specifically, we develop a mathematical model of resource
      availability and metabolic response within colony features. This analysis
      accurately predicts the measured distribution of two types of electron acceptors:
      oxygen, which is available from the atmosphere, and phenazines, redox-active
      antibiotics produced by the bacterium. Using this model, we demonstrate that the
      geometry of colony structures is optimal with respect to growth efficiency.
      Because our model is based on resource dynamics, we also can anticipate shifts in
      feature geometry based on changes to the availability of electron acceptors,
      including variations in the external availability of oxygen and genetic
      manipulation that renders the cells incapable of phenazine production. 

PMID- 24335706
TI  - Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice.
AB  - Immunoregulatory T cells have been identified as key modulators of peripheral
      tolerance and participate in preventing autoimmune diseases. CD4(-)CD8(-) (double
      negative, DN) T cells compose one of these immunoregulatory T-cell subsets, where
      the injection of DN T cells confers protection from autoimmune diabetes
      progression. Interestingly, genetic loci defining the function and number of
      CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) coincide with at least some
      autoimmune disease susceptibility loci. Herein, we investigate the impact of
      major insulin-dependent diabetes (Idd) loci in defining the number of DN T cells.
      We demonstrate that although Idd3, Idd5 and Idd9 loci do not regulate DN T-cell
      number, NOD mice congenic for diabetes resistance alleles at the Idd13 locus show
      a partial restoration in DN T-cell number. Moreover, competitive and non
      competitive bone marrow chimera experiments reveal that DN T-cell number is
      defined by a bone marrow-intrinsic, but DN T-cell-extrinsic, factor. This
      suggests that non-autonomous candidate genes define DN T-cell number in secondary
      lymphoid organs. Together, our results show that the regulation of DN T-cell
      number in NOD mice is at least partially conferred by alleles at the Idd13 locus.

PMID- 24335708
TI  - The molecular genetics of chronic neutrophilic leukaemia: defining a new era in
      diagnosis and therapy.
AB  - PURPOSE OF REVIEW: In the current WHO classification of myeloid disorders,
      chronic neutrophilic leukaemia (CNL) is recognized as a myeloproliferative
      neoplasm characterized by sustained neutrophilic leukocytosis, hepatosplenomegaly
      and bone marrow granulocytic hyperplasia without evidence of dysplasia, BCR-ABL1
      or rearrangements of PDGFRA, PDGFRB or FGFR1. This diagnosis is contingent upon
      exclusion of underlying causes of reactive neutrophilia particularly if evidence
      of myeloid clonality is lacking. The lack of a specific molecular marker has left
      the diagnosis to be largely one of exclusion. Recently, the molecular landscape
      shifted with the discovery of specific oncogenic mutations in the colony
      stimulating factor 3 receptor gene (CSF3R) in CNL patients. We review the
      implications for diagnosis, pathogenesis and potential for new therapeutic
      options. RECENT FINDINGS: In 2013, oncogenic mutations in CSF3R were identified
      in a majority of patients with CNL and demonstrated that their downstream
      signalling was sensitive to known kinase inhibitors. This discovery was then
      validated with the demonstration of 100% CSF3R mutational frequency
      (predominately CSF3RT618I) in strictly WHO-defined CNL. Simultaneously, novel
      somatic mutations in SETBP1 were found to be enriched in CNL with possible
      prognostic significance. SUMMARY: CNL appears to be driven by specific somatic
      activating CSF3R mutations. These bestow susceptibility to known kinase
      inhibitors, opening the door to novel specific therapeutic options for CNL. The
      diagnosis of CNL will no longer be one only of exclusion, and revision of the
      current WHO diagnostic criteria is expected to include the molecular criterion of
      CSF3R mutation positivity.

PMID- 24335707
TI  - Hepatic metallothionein expression in chronic hepatitis C virus infection is
      IFNL3 genotype-dependent.
AB  - The IFNL3 genotype predicts the clearance of hepatitis C virus (HCV),
      spontaneously and with interferon (IFN)-based therapy. The responder genotype is
      associated with lower expression of interferon stimulated genes (ISGs) in liver
      biopsies from chronic hepatitis C patients. However, ISGs represent many
      interacting molecular pathways, and we hypothesised that the IFNL3 genotype may
      produce a characteristic pattern of ISG expression explaining the effect of
      genotype on viral clearance. For the first time, we identified an association
      between a cluster of ISGs, the metallothioneins (MTs) and IFNL3 genotype.
      Importantly, MTs were significantly upregulated (in contrast to most other ISGs)
      in HCV-infected liver biopsies of rs8099917 responders. An association between
      lower fibrosis scores and higher MT levels was demonstrated underlying clinical
      relevance of this association. As expected, overall ISGs were significantly
      downregulated in biopsies from subjects with the IFNL3 rs8099917 responder
      genotype (P=2.38 * 10(-7)). Peripheral blood analysis revealed paradoxical and
      not previously described findings with upregulation of ISGs seen in the responder
      genotype (P=1.00 * 10(-4)). The higher MT expression in responders may contribute
      to their improved viral clearance and MT-inducing agents may be useful adjuncts
      to therapy for HCV. Upregulation of immune cell ISGs in responders may also
      contribute to the IFNL3 genotype effect. 

PMID- 24335709
TI  - Beyond hypomethylating agents failure in patients with myelodysplastic syndromes.
AB  - PURPOSE OF REVIEW: Although hypomethylating agents (HMAs) significantly improve
      outcomes in myelodysplastic syndromes (MDS), only half the patients achieve
      objective responses, and most responders lose response within 1-2 years.
      Azacitidine prolongs survival by a median of only 9.5 months. Failure of HMA
      therapy is associated with a very dismal prognosis. Therefore, novel therapeutic
      approaches are clearly needed. RECENT FINDINGS: The sequential use of the
      alternative HMA after failure of first line HMA is associated with modest
      efficacy. The improved understanding of the biologic underpinnings of the disease
      have opened the door to study investigational agents that target disrupted
      molecular pathways critical to the pathogenesis of MDS. Combination treatment
      strategies using an azacitidine backbone are demonstrating promising early
      results. Expanding the applicability of allogeneic stem cell transplantation
      (alloSCT), the only curative modality, by reducing toxicity and relapse rates is
      another area of active research. SUMMARY: Sequential switching to the alternative
      HMA, clinical trials of novel targeted therapies, azacitidine-based combination
      therapeutic strategies, and improvements in the alloSCT platform are the main
      directions in improving outcomes of MDS post HMA failure.

PMID- 24335711
TI  - Red cell distribution width may be related to the degree of coronary collateral
      circulation.

PMID- 24335712
TI  - Matching HIV, tuberculosis, viral hepatitis, and sexually transmitted diseases
      surveillance data, 2000-2010: identification of infectious disease syndemics in
      New York City.
AB  - CONTEXT: In 2012, the New York City Department of Health and Mental Hygiene
      matched HIV, tuberculosis, viral hepatitis, and sexually transmitted disease
      surveillance data to identify the burden of infection with multiple diseases.
      METHODS: HIV, tuberculosis, hepatitis B, hepatitis C, chlamydia, gonorrhea, and
      syphilis surveillance data from 2000 to 2010 were matched using a deterministic
      method. Data on deaths from the Department of Health and Mental Hygiene's Office
      of Vital Statistics were also matched. RESULTS: The final data set contained
      840,248 people; 13% had 2 or more diseases. People with a report of syphilis had
      the highest proportion of matches with other diseases (64%), followed by
      gonorrhea (52%), HIV (31%), tuberculosis (23%), hepatitis C (20%), chlamydia
      (16%), and hepatitis B (11%). CONCLUSIONS: The findings indicate several possible
      infectious disease syndemics in New York City and highlight the need to integrate
      surveillance data from different infectious disease programs. Conducting the
      match brought surveillance programs together to work collaboratively and has
      resulted in ongoing partnerships on programmatic activities that address multiple
      diseases.

PMID- 24335710
TI  - Zinc, iron and vitamins A, C and e are associated with obesity, inflammation,
      lipid profile and insulin resistance in Mexican school-aged children.
AB  - The objective of this cross-sectional study was to evaluate the relationship
      between micronutrient status and obesity, lipids, insulin resistance and chronic
      inflammation in children. Weight, height, waist circumference and body
      composition (dual-energy X-ray absorptiometry (DEXA)) were determined in 197
      school-aged children. Lipids, glucose, insulin, C-reactive protein (CRP), zinc,
      iron and vitamins A, C and E were analyzed in blood. Vitamin C and vitamin
      E:lipids were negatively associated with Body Mass Index (BMI), waist-to-height
      ratio (WHR) and body and abdominal fat (p < 0.05). Vitamin A was positively
      associated with BMI, BMI-for-age, WHR and abdominal fat (p < 0.05). Iron and
      vitamin E:lipids were negatively associated with insulin (p < 0.05). Vitamins A,
      C and E and iron were negatively associated with CRP (p < 0.05). Interaction
      analysis showed that children who were overweight and obese who also had low
      concentrations of vitamin A had higher CRP and lower triglycerides (p < 0.1),
      children with low vitamin E had significantly lower glucose and triglycerides (p
      < 0.1) and higher low-density lipoprotein (LDL) concentrations (p < 0.05), and
      children with low zinc concentrations had higher insulin resistance compared with
      children with adequate weight (p < 0.05). In conclusion, low vitamin C
      concentration and vitamin E:lipids were associated with obesity. Furthermore, low
      concentrations of zinc, vitamins A and E in children who were overweight and
      obese were associated with lipids, inflammation and insulin resistance. 

PMID- 24335713
TI  - The New Product Watch: Successes and Challenges of Crowdsourcing as a Method of
      Surveillance.
AB  - New smokeless tobacco (eg, snus and dissolvable tobacco products) and nontobacco
      nicotine products (eg, e-cigarettes) have emerged in recent years amid widespread
      speculation about locations of test marketing, toxic constituents, and consumer
      targeting. The New Product Watch was a pilot online monitoring system aimed at
      filling these information gaps by using a form of crowdsourcing: recruiting
      volunteers to visit local retailers and report their findings. With very little
      funding, the New Product Watch gathered county-specific data on new product
      availability in 19 states as well as trend data on product marketing and demand,
      and completed 2 rounds of product purchases and subsequent toxic constituent
      analyses. Data were collected over a 2-year period, between 2009 and 2011.
      Despite the successes, we found that this small-scale, volunteer effort was not a
      sustainable method for ensuring continuous, systematic surveillance of new
      product availability, marketing, and toxicity. 

PMID- 24335715
TI  - Phosphorus magnetic resonance spectroscopic imaging at 7 T in patients with
      prostate cancer.
AB  - OBJECTIVES: The aim of this study was to identify characteristics of phosphorus
      (P) spectra of the human prostate and to investigate changes of individual
      phospholipid metabolites in prostate cancer through in vivo P magnetic resonance
      spectroscopic imaging (MRSI) at 7 T. MATERIALS AND METHODS: In this institutional
      review board-approved study, 15 patients with biopsy-proven prostate cancer
      underwent T2-weighted magnetic resonance imaging and 3-dimensional P MRSI at 7 T.
      Voxels were selected at the tumor location, in normal-appearing peripheral zone
      tissue, normal-appearing transition zone tissue, and in the base of the prostate
      close to the seminal vesicles. Phosphorus metabolite ratios were determined and
      compared between tissue types. RESULTS: Signals of phosphoethanolamine (PE) and
      phosphocholine (PC) were present and well resolved in most P spectra in the
      prostate. Glycerophosphocholine signals were observable in 43% of the voxels in
      malignant tissue, but in only 10% of the voxels in normal-appearing tissue away
      from the seminal vesicles. In many spectra, independent of tissue type, 2 peaks
      resonated in the chemical shift range of inorganic phosphate, possibly
      representing 2 separate pH compartments. The PC/PE ratio in the seminal vesicles
      was highly elevated compared with the prostate in 5 patients. A considerable
      overlap of P metabolite ratios was found between prostate cancer and normal
      appearing prostate tissue, preventing direct discrimination of these tissues. The
      only 2 patients with high Gleason scores tumors (>=4+5) presented with high PC
      and glycerophosphocholine levels in their cancer lesions. CONCLUSIONS: Phosphorus
      MRSI at 7 T shows distinct features of phospholipid metabolites in the prostate
      gland and its surrounding structures. In this exploratory study, no differences
      in P metabolite ratios were observed between prostate cancer and normal-appearing
      prostate tissue possibly because of the partial volume effects of small tumor
      foci in large MRSI voxels.

PMID- 24335714
TI  - National survey of training needs reported by public health professionals in
      chronic disease programs in state, territorial, and local governments.
AB  - CONTEXT: In 2009, the National Association of Chronic Disease Directors published
      desirable competencies for professionals in public health chronic disease
      programs. Assessing the training needs of these professionals is an important
      step toward providing appropriate training programs in chronic disease prevention
      and control competencies. OBJECTIVES: Conduct a survey of the chronic disease
      workforce in state and local health departments to identify professional training
      needs. DESIGN: We conducted a cross-sectional survey of state, territorial, and
      local public health professionals who work in chronic disease programs to
      identify their self-reported training needs, using the membership lists of 3
      professional organizations that included practitioners in chronic disease public
      health programs. SETTING: The survey was national, used a convenience sample, and
      was conducted in 2011. PARTICIPANTS: The survey was developed using an algorithm
      to select anonymous participants from the membership lists of the National
      Association of Chronic Disease Directors, the Directors for Health Promotion and
      Education, and the National Association of County & City Health Officials.
      OUTCOME MEASURES: The survey included questions about professional background,
      chronic disease activities, confidence about skills, and needs for training.
      RESULTS: The survey had 567 responses (38% response ratio). The majority of the
      respondents were female, non-Hispanic white, and 40 years or older. Respondents
      were not confident of their skills in health economics (38%) and technology and
      data management (23%). The most requested training topics were assessing the
      effects of policies, laws, and regulations (70%) and health economics (66%).
      CONCLUSIONS: This survey included local, territorial, and state public health
      professionals who work in chronic disease programs. These reported training needs
      in quantitative measurement methods and policy-related topics suggest key
      subjects for future training and education curricula.

PMID- 24335716
TI  - Taxanes as radiosensitizers.
AB  - In parallel with the discovery of the taxanes, our understanding of the molecular
      underpinnings that comprise the classic biologic principles of fractionated
      radiotherapy has rapidly evolved over the past half century. Early studies have
      implicated DNA as the primary target for radiation-induced lethality. More
      recently, however, the molecular biology involved in radiosensitization of tumor
      cells has been unveiled. Specifically, factors associated with DNA damage and
      cell killing, collectively known as the 'four Rs' of radiobiology, including
      (r)eassortment of tumor cells into the radiosensitive phases of the cell cycle
      (G2/M), (r)eoxygenation of hypoxic areas within a tumor, (r)epair of sublethal
      DNA damage, and (r)epopulation of surviving tumor cells, have been elucidated,
      and upon manipulation of each factor or a combination of factors a significant
      impact on radiation-associated tumor control probabilities was found. Not only
      does spatial cooperation have a theoretical benefit in patients with undetectable
      micrometastatic disease at presentation, but the manipulation of either of the
      'four Rs' using taxanes provokes further local radiation-associated tumor cell
      killing with an associated improvement in clinical responses. Numerous studies
      have shown that taxanes radiosensitize tumor cells directly and/or indirectly by
      perturbing the tumor microenvironment in a time-dependent and dose-dependent
      manner. Herein, the impact of taxanes on radiobiological tenets as a mode of
      radiosensitizing tumor cells and their clinical implications are reviewed. 

PMID- 24335717
TI  - Measuring sensitivity to viewpoint change with and without stereoscopic cues.
AB  - The speed and accuracy of object recognition is compromised by a change in
      viewpoint; demonstrating that human observers are sensitive to this
      transformation. Here we discuss a novel method for simulating the appearance of
      an object that has undergone a rotation-in-depth, and include an exposition of
      the differences between perspective and orthographic projections. Next we
      describe a method by which human sensitivity to rotation-in-depth can be
      measured. Finally we discuss an apparatus for creating a vivid percept of a 3
      dimensional rotation-in-depth; the Wheatstone Eight Mirror Stereoscope. By doing
      so, we reveal a means by which to evaluate the role of stereoscopic cues in the
      discrimination of viewpoint rotated shapes and objects. 

PMID- 24335719
TI  - Families are warned they can't decide treatment for incapacitated relatives.

PMID- 24335718
TI  - Targeting of hepatic angiotensinogen using chemically modified siRNAs results in
      significant and sustained blood pressure lowering in a rat model of hypertension.
AB  - Angiotensinogen (AGT) is the precursor of active vasoconstrictive octapeptide
      angiotensin II (Ang II) in the renin-angiotensin-aldosterone system. Blocking the
      AGT-converting enzymes in the pathway and the Ang II receptor through
      pharmacological agents has been proven to be effective in lowering blood pressure
      (BP) in hypertensive patients. In this study, we developed chemically modified
      small interfering RNAs (siRNA) to target hepatic AGT mRNA in rats. Lipid
      nanoparticle encapsulated siRNAs were efficiently delivered to rat liver and
      resulted in significant reduction in hepatic Agt mRNA levels and plasma AGT
      concentration without impairing liver function. Single intravenous injection of
      Agt siRNA led to significant and sustained BP lowering in spontaneous
      hypertensive rats and in Sprague-Dawley rats, and the effect was maintained by
      weekly siRNA dosing. Data presented here provide proof-of-feasibility for the use
      of siRNA technology for inhibition of peripheral AGT levels via hepatic mRNA
      silencing with beneficial effects on BP in preclinical rat models. Similar
      approach could be used for validation of novel hypertension hepatic and
      extrahepatic targets.

PMID- 24335720
TI  - Current thinking on genital herpes.
AB  - PURPOSE OF REVIEW: Genital herpes has a high global prevalence and burden of
      disease. This manuscript highlights recent advances in our understanding of
      genital herpes simplex virus (HSV) infections. RECENT FINDINGS: Studies
      demonstrate a changing epidemiological landscape with an increasing proportion of
      genital herpes cases associated with HSV type 1. There is also growing evidence
      that the majority of infected individuals exhibit frequent, brief shedding
      episodes that are most often asymptomatic, which likely contribute to high HSV
      transmission rates. Given this finding as well as readily available serological
      assays, some have proposed that routine HSV screening be performed; however, this
      remains controversial and is not currently recommended. Host immune responses,
      particularly local CD4 and CD8 T cell activity, are crucial for HSV control and
      clearance following initial infection, during latency and after reactivation.
      Prior HSV immunity may also afford partial protection against HSV reinfection and
      disease. Although HSV vaccine trials have been disappointing to date and existing
      antiviral medications are limited, novel prophylactic and therapeutic modalities
      are currently in development. SUMMARY: Although much remains unknown about
      genital herpes, improved knowledge of HSV epidemiology, pathogenesis and host
      immunity may help guide new strategies for disease prevention and control.

PMID- 24335721
TI  - The Correlation Between Restoration of Lumbar Lordosis and Surgical Outcome in
      the Treatment of Low-grade Lumbar Degenerative Spondylolisthesis With Spinal
      Fusion.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To investigate the
      relationship between the restoration of the lumbar lordosis (LL) and the surgical
      outcome of patients undergoing spinal fusion for low-grade lumbar degenerative
      spondylolisthesis. SUMMARY OF BACKGROUND DATA: Correlation between low back pain
      and the loss of LL in the treatment of low-grade lumbar degenerative
      spondylolisthesis has seldom been reported. METHODS: Between May 2005 and July
      2011, 59 patients with low back pain and neurogenic claudication due to low-grade
      lumbar degenerative spondylolisthesis underwent spinal decompression and fusion
      by a senior surgeon. Ten patients were lost to follow-up. The mean age of the
      remaining 49 patients (10 men and 39 women) was 64.0 years (range, 47-88 y).
      Patients were categorized on the basis of the spino-pelvic posture: type 1
      [pelvic incidence (PI)<45 degrees] (n=12), type 2 (45 degrees<=PI<=60 degrees)
      (n=24), and type 3 (PI>60 degrees) (n=13). The LL restoration ratio was
      calculated by the actual LL divided by the predicted LL. The clinical results
      were evaluated using a visual analogue scale and the Oswestry Disability Index.
      Postoperative 36-inch spinal films were used to assess the sagittal balance.
      RESULTS: The mean follow-up period was 43.2 months (range, 28-62 mo). Forty-eight
      patients showed significant improvement with respect to visual analogue scale and
      Oswestry Disability Index regardless of whether the LL was restored higher or
      lower. Postoperative 36-inch spinal films showed the C7 plumb line to be within
      an average of 4.4 cm (range, 0.6-5.6 cm) from the posterior-superior corner of
      the S1 vertebrae. CONCLUSIONS: Patients with smaller PI tended to be restored
      higher, and those patients with a larger PI were more likely to be restored
      lower. For patients with normal sagittal balance, the surgical outcomes in the
      treatment of low-grade lumbar degenerative spondylolisthesis with spinal fusion
      are not correlated with restoration of the LL.

PMID- 24335722
TI  - Detection of Pseudarthrosis in Adult Spinal Deformity: The Use of Health-related
      Quality-of-life Outcomes to Predict Pseudarthrosis.
AB  - STUDY DESIGN: Single-center, retrospective study of consecutive surgeries.
      OBJECTIVE: This study aimed to evaluate the reliability of previously published
      anterior fusion grading systems and assess the ability of health-related quality
      of-life (HRQOL) outcomes to predict pseudarthrosis (PSAR). SUMMARY OF BACKGROUND
      DATA: Despite existing radiographic indicators, PSAR may still go unidentified on
      biplanar radiographs, and little data is available on the reliability of such
      grading systems in adult spinal deformity patients. As such, there is a need for
      a practical, noninvasive tool to help identify PSAR. METHODS: This study included
      consecutive primary surgical patients with idiopathic or degenerative scoliosis
      undergoing anterior and posterior correction with instrumentation to the sacrum
      or pelvis and minimum 2-year follow-up. Patients were grouped into fused (no
      radiographic or clinical signs of PSAR) and PSAR (known PSAR diagnosed by
      surgical exploration or thin-cut computed tomography scan at least 1 year after
      surgery) cohorts. Two-year radiographs were graded by an independent blinded
      orthopedic deformity surgeon and a neuroradiologist. HRQOL scores [22-item
      Scoliosis Research Society questionnaire (SRS-22) and the Oswestry Disability
      Index (ODI)] at 1-year follow-up were analyzed as potential predictors of future
      PSAR. RESULTS: Thirty-four patients with average follow-up of 2.2 years (2-2.5 y)
      were evaluated. Eight (23.5%) patients had known PSAR consisting of 40 (24.8%)
      anterior levels. Analysis by independent reviewers incorrectly identified 2
      levels as unfused and failed to identify any PSAR levels. The PSAR group had
      lower average SRS scores in all domains and lower average ODI scores at 1-year
      postoperatively relative to fused patients. The PSAR group also showed no
      significant improvement in SRS or ODI scores relative to baseline. In comparison,
      the fused group showed significant improvement in all domains. CONCLUSIONS:
      Standard radiographs are insufficient for identifying PSAR in adult spinal
      deformity patients. Failure to achieve significant improvement in SRS and ODI
      should lead the surgeon to suspect PSAR and consider additional investigation.

PMID- 24335723
TI  - Hemostatic techniques following multilevel posterior lumbar spine surgery: a
      randomized control trial.
AB  - STUDY DESIGN: This was a prospective, randomized controlled clinical study.
      OBJECTIVE: To determine the efficacy of absorbable gelatin sponge in reducing
      blood loss, as well as shortening the length of hospital stay in patients
      undergoing multilevel posterior lumbar spinal surgery. BACKGROUND: Absorbable
      gelatin sponge is reported to decrease postoperative drain output and the length
      of hospital stay after multilevel posterior cervical spine surgery. However,
      there is a dearth of literature on prospective study of the efficacy of
      absorbable gelatin sponge in reducing postoperative blood loss, as well as
      shortening the length of hospital stay in patients undergoing multilevel
      posterior lumbar spinal surgery. MATERIALS AND METHODS: A total of 82 consecutive
      patients who underwent multilevel posterior lumbar fusion or posterior lumbar
      interbody fusion between June 2011 and June 2012 were prospectively randomized
      into one of the 2 groups according to whether absorbable gelatin sponge for
      postoperative blood management was used or not. Demographic distribution, total
      drain output, blood transfusion rate, the length of stay, the number of
      readmissions, and postoperative complications were analyzed. RESULTS: Total drain
      output averaged 173 mL in the study group and 392 mL in the control group
      (P=0.000). Perioperative allogeneic blood transfusion rate were lower in the
      Gelfoam group (34.1% vs. 58.5%, P=0.046); moreover, length of stay in patients
      with the use of absorbable gelatin sponge (12.58 d) was significantly shorter
      (P=0.009) than the patients in the control group (14.46 d). No patient developed
      adverse reactions attributable to the absorbable gelatin sponge. CONCLUSIONS:
      Application of absorbable gelatin sponge at the end of multilevel posterior
      lumbar fusion can significantly decrease postoperative drain output and length of
      hospital stay.

PMID- 24335724
TI  - Do Anterior Cervical Osteophytes Prevent Dynamization of Cervical Dynamic Plates?
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate radiographic changes
      of patients with osteophytes at the anterior border of the caudal vertebral body
      who were treated with anterior cervical discectomy and fusion using dynamic
      rotational plates. SUMMARY OF BACKGROUND DATA: Dynamic cervical plates are widely
      used in surgeries of the anterior cervical spine. One concern in using dynamic
      plates is that the subjacent anterior osteophytes might act as a bony block and
      prevent dynamization of the plate. To our knowledge, there are no studies that
      have investigated the validity of this concern. MATERIALS AND METHODS: Twenty
      eight patients were selected for the study out of patients who had undergone 1
      level anterior cervical discectomy and fusion using a dynamic rotational plate.
      They were divided into 2 groups on the basis of the presence of osteophytes
      located at the anterior border of the subjacent vertebrae. Thirteen patients had
      osteophytes and 15 control patients did not. The mean follow-up period was 10.8+/
      8.4 months (range, 6-36 mo). Lateral radiographs were taken preoperatively,
      immediately postoperatively, and at the final follow-ups to assess changes in the
      following radiographic parameters: Cobb angle of the adjacent segments and fused
      segment, horizontal distance between C2 and C7 plumb lines, height of the bone
      graft, vertebral heights of the operated segment, and migration distance of the
      plate. RESULTS: No statistical significance was found in the Cobb angles of the
      adjacent segments and fused segment, distance between the C2-C7 plumb lines,
      height of the graft, height of vertebral bodies of the operated segment, and
      migration distance of the plate through the preoperative, postoperative, and
      final follow-ups between the 2 groups. CONCLUSION: Osteophytes did not appear to
      affect the dynamization of plates in any of the measured radiographic parameters.

PMID- 24335725
TI  - Immediate reduction under general anesthesia and single-staged anteroposterior
      spinal reconstruction for fracture-dislocation of lower cervical spine.
AB  - Fracture-dislocation of the lower cervical spine is a severe traumatic lesion,
      most frequently resulting in tetraplegia. Treatment is usually painful and time
      consuming. This retrospective study evaluated the clinical curative effect of
      immediate reduction under general anesthesia and single-staged anteroposterior
      spinal reconstruction for fracture-dislocation of the lower cervical spine.
      Twelve cases of traumatic lower cervical spinal fracture-dislocation were
      retrospectively analyzed from January 2006 to December 2011. The injury level was
      C4/C5 in 4, C5/C6 in 5, and C6/C7 in 3 patients. The spinal cord function grades
      according to the American Spinal Injury Association impairment scale (2000
      edition amended) before operation were as follows: grade A in 2 cases, grade B in
      2 cases, grade C in 5 cases, grade D in 2 cases, and grade E in 1 case. On
      admission, all patients underwent immediate reduction under general anesthesia
      and single-staged anteroposterior spinal reconstruction by circumferential
      fixation/fusion. The spinal cord function grades according to American Spinal
      Injury Association after operation were as follows: grade A in 1 case, grade B in
      1 case, grade C in 3 cases, grade D in 3 cases, and grade E in 4 cases. All 12
      patients showed evidence of stability at the instrumented level on the final
      follow-up examination (mean follow-up, 3.7 y). Immediate reduction under general
      anesthesia followed by a single-stage combined anteroposterior spinal
      reconstruction is a safe and reliable way of treating patients with lower
      cervical spine fracture-dislocations. 

PMID- 24335727
TI  - Fall risk assessment and early-warning for toddler behaviors at home.
AB  - Accidental falls are the major cause of serious injuries in toddlers, with most
      of these falls happening at home. Instead of providing immediate fall detection
      based on short-term observations, this paper proposes an early-warning childcare
      system to monitor fall-prone behaviors of toddlers at home. Using 3D human
      skeleton tracking and floor plane detection based on depth images captured by a
      Kinect system, eight fall-prone behavioral modules of toddlers are developed and
      organized according to four essential criteria: posture, motion, balance, and
      altitude. The final fall risk assessment is generated by a multi-modal fusion
      using either a weighted mean thresholding or a support vector machine (SVM)
      classification. Optimizations are performed to determine local parameter in each
      module and global parameters of the multi-modal fusion. Experimental results show
      that the proposed system can assess fall risks and trigger alarms with an
      accuracy rate of 92% at a speed of 20 frames per second. 

PMID- 24335726
TI  - A genome-wide regulatory network identifies key transcription factors for memory
      CD8+ T-cell development.
AB  - Memory CD8+ T-cell development is defined by the expression of a specific set of
      memory signature genes. Despite recent progress, many components of the
      transcriptional control of memory CD8+ T-cell development are still unknown. To
      identify transcription factors and their interactions in memory CD8+ T-cell
      development, we construct a genome-wide regulatory network and apply it to
      identify key transcription factors that regulate memory signature genes. Most of
      the known transcription factors having a role in memory CD8+ T-cell development
      are rediscovered and about a dozen new ones are also identified. Sox4, Bhlhe40,
      Bach2 and Runx2 are experimentally verified, and Bach2 is further shown to
      promote both development and recall proliferation of memory CD8+ T cells through
      Prdm1 and Id3. Gene perturbation study identifies the interactions between the
      transcription factors, with Sox4 positioned as a hub. The identified
      transcription factors and insights into their interactions should facilitate
      further dissection of molecular mechanisms underlying memory CD8+ T-cell
      development.

PMID- 24335730
TI  - We need to pay attention to substance use among homeless youth.

PMID- 24335732
TI  - An examination of stress, coping, and adaptation in nurses in a recovery and
      monitoring program.
AB  - Addiction rates in nurses are higher than in the general population. The
      relationship between stress, coping, and adaptation in nurses (N = 82) enrolled
      in a recovery and monitoring program in the state of New Jersey was examined.
      Social support, a variable tested as a mediator of this relationship, was also
      examined. Participants completed the Perceived Stress Scale, Multidimensional
      Scale of Perceived Social Support, and Psychological General Well-Being Index.
      Negative relationships were found between stress and social support and stress
      and well-being, and a positive relationship was found between social support and
      well-being (all ps < .05). The direct relationship between stress and well-being
      was decreased in the presence of social support. The findings of this research
      suggest that, to assist nurses, an increased awareness of stress and its
      injurious effects on overall well-being must be identified so proactive measures
      can be implemented to prevent potential untoward consequences. Ultimately,
      methods to strengthen social support and social networks will enhance the
      probability of sustained recovery, relapse prevention, and safe reentry into
      nursing practice. Implications for behavioral health providers and health care
      practitioners are discussed. 

PMID- 24335731
TI  - Acute alcohol consumption and motivation to reduce drinking among injured
      patients in a Swedish emergency department.
AB  - Injuries constitute a major public health problem. Millions of people are injured
      each year, and acute drinking is a well-known risk factor for injuries. Research
      suggests that acknowledgment of alcohol as a factor in an injury enhances
      willingness to change drinking behavior, possibly because the patient becomes
      aware of the negative consequences of their drinking. This study aims to
      investigate the prevalence of acute alcohol consumption (drinking before the
      event) among injury patients and to examine the importance of factors potentially
      associated with motivation to reduce alcohol consumption among these patients.
      All patients aged 18-69 years were requested to answer alcohol-related questions
      on a touchscreen computer. Fifteen percent of injured patients were categorized
      as acute drinkers, and of these, 64% reported that their injury was connected to
      alcohol. There were significant differences for all sociodemographic and drinking
      characteristics between acute drinkers and nonacute drinkers. Acute drinkers were
      categorized as risky drinkers to a much higher extent than nonacute drinkers.
      Acute drinkers had a considerably higher average weekly alcohol consumption and
      engaged far more frequently in heavy episodic drinking than nonacute drinkers.
      Acute drinkers were motivated to reduce their alcohol intake to a greater extent
      than nonacute drinkers; 51% were in the action, preparation, and contemplation
      stages, compared with 19% of the nonacute drinkers. Acute drinkers had
      considerably more detrimental alcohol consumption than nonacute drinkers, and the
      acute drinkers were more motivated to reduce their drinking than the nonacute
      drinkers. 

PMID- 24335733
TI  - Anabolic-androgenic steroids and adolescents: recent developments.
AB  - Despite their classification as a Schedule III Controlled Substance, anabolic
      androgenic steroids continue to be used by adolescents who seek increased
      muscularity as well as enhanced athletic performance. Although the potential side
      effects of steroids are relatively well known, problems with counterfeit
      substances and steroid-spiked dietary supplements have received less attention.
      Drawing on scholarly literature and reports from government units such as the
      Drug Enforcement Administration and the Food and Drug Administration, this
      article addresses those issues and makes recommendations for communicating with
      adolescents about the use of steroids. 

PMID- 24335735
TI  - Smoking prevalence, attitudes, and confidence about tobacco roles among
      Australian nursing students.
AB  - This study identified major challenges to be addressed before student nurses can
      achieve their full potential in providing effective and comprehensive smoking
      cessation interventions. Smoking behaviors were assessed among undergraduate
      nursing students. In addition, students' attitudes, confidence levels, and
      support for extra training in tobacco control were examined. A nonprobability
      sample of 381 students at an Australian university was surveyed. The consent rate
      was 81%. Prevalence of current smoking was 21%. In the regression analysis, age
      group was the only statistically significant predictor of smoking status. Over
      one third (36%) did not endorse the nonsmoking exemplar role of their future
      profession. Most (60%) did not support the concept of routine smoking cessation
      intervention. Students who were smokers had significantly higher tobacco control
      confidence levels than nonsmokers. Smoking-related variables did not differ
      between students in different years of the course. Improved tobacco control
      training is needed at undergraduate level. 

PMID- 24335736
TI  - Are the dental health needs of adults with illegal drug dependence being met by
      current service provision in the United Kingdom?: a literature review.
AB  - This literature review outlines the current issues and debates relating to the
      dental health of adults with drug dependence. The dental health of adults with
      illegal drug dependence (IDD) continues to be under debate throughout dental
      practice, and the most appropriate model of care suitable to meet the high
      complex needs of this client group remains uncertain. The study aims to review
      and critically analyze available research relating to the oral health effects of
      illegal drug misuse and the dental health needs and status of adults with drug
      dependence. Second, it aims to identify and critically evaluate current models of
      dental service/care delivery, including relevant best practice guidance and
      potential barriers to dental access for adults with IDD. The available literature
      pertaining to dental health and adults with drug dependence are systematically
      reviewed and critically analyzed and evaluated in order to execute a rigorous
      investigation. The oral effects along with general medical complications
      associated with IDD are increasingly being recognized. There are substantive
      negative effects of IDD on oral health, particularly for those with opioid
      dependence; therefore, these clients have high complex dental needs and low use
      of dental services. Adults with drug dependence comprise a group with special
      dental needs and therefore need greater access to dental care than most people
      due to their high level of need. A high awareness of the implications for oral
      health care for adults with drug dependence is essential. Dental professionals
      have a key role in supporting the rehabilitation of these patients from
      potentially severe or fatal addictions. There is a distinct lack of national
      policy and guidance relating specifically to adults with drug dependence, and
      therefore, problems persist. Key findings and recommendations are presented to
      enhance the development of dental services for adults with IDD. 

PMID- 24335737
TI  - Screening, brief intervention, and referral to treatment and the role of nursing.
AB  - The first article is a good starting place for building an SBIRT program. It
      provides a good overview of the evidence and explains SBIRT as defined by SAMHSA.
      It should only serve as a starting point since it leaves questions unanswered. It
      does not clearly explain how to actually do each part of SBIRT. Other resources,
      such as National Institute on Alcohol Abuse and Alcoholism's guide to clinicians
      or the American College of Surgeon's guide, are recommended reading prior to
      implementing SBIRT. The major issue appears to be the lack of clear evidence that
      referral to treatment actually results in positive long-term outcomes for those
      with a substance use disorder. In addition, the development of an SBIRT program
      in an institution should utilize an interdisciplinary approach with a nurse lead
      program as a promising alternative to a hierarchical program that requires
      physician oversight.

PMID- 24335739
TI  - Colorado's peer health assistance program for nurses: past and present.

PMID- 24335740
TI  - SBIRT-the new sixth vital sign? A policy perspective.

PMID- 24335741
TI  - American Society for Pain Management nursing position statement: pain management
      in patients with substance use disorders.
AB  - The American Society for Pain Management Nursing (ASPMN) has updated its position
      statement on managing pain in patients with substance use disorders. This
      position statement is endorsed by the International Nurses Society on Addictions
      (IntNSA) and includes clinical practice recommendations based on current
      evidence. It is the position of ASPMN and IntNSA that every patient with pain,
      including those with substance use disorders, has the right to be treated with
      dignity, respect, and high-quality pain assessment and management. Failure to
      identify and treat the concurrent conditions of pain and substance use disorders
      will compromise the ability to treat either condition effectively. Barriers to
      caring for these patients include stigmatization, misconceptions, and limited
      access to providers skilled in these two categories of disorders. Topics
      addressed in this position statement include the scope of substance use and
      related disorders, conceptual models of addiction, ethical considerations,
      addiction risk stratification, and clinical recommendations.

PMID- 24335742
TI  - Replacing clinic-based tests with home-use tests may increase HIV prevalence
      among Seattle men who have sex with men: evidence from a mathematical model.
AB  - BACKGROUND: Home-use tests have potential to increase HIV testing but may
      increase the rate of false-negative tests and decrease linkage to HIV care. We
      sought to estimate the impact of replacing clinic-based testing with home-use
      tests on HIV prevalence among men who have sex with men (MSM) in Seattle,
      Washington. METHODS: We adapted a deterministic, continuous-time model of HIV
      transmission dynamics parameterized using a 2003 random digit dial study of
      Seattle MSM. Test performance was based on the OraQuick In-Home HIV Test (OraSure
      Technologies, Inc, Bethlehem, PA) for home-use tests and, on an average, of
      antigen-antibody combination assays and nucleic acid amplification tests for
      clinic-based testing. RESULTS: Based on observed levels of clinic-based testing,
      our baseline model predicted an equilibrium HIV prevalence of 18.6%. If all men
      replaced clinic-based testing with home-use tests, prevalence increased to 27.5%
      if home-use testing did not impact testing frequency and to 22.4% if home-use
      testing increased testing frequency 3-fold. Regardless of how much home-use
      testing increased testing frequency, any replacement of clinic-based testing with
      home-use testing increased prevalence. These increases in HIV prevalence were
      mostly caused by the relatively long window period of the currently approved
      test. If the window period of a home-use test were 2 months instead of 3 months,
      prevalence would decrease if all MSM replaced clinic-based testing with home-use
      tests and tested more than 2.6 times more frequently. CONCLUSIONS: Our model
      suggests that if home-use HIV tests replace supplement clinic-based testing, HIV
      prevalence may increase among Seattle MSM, even if home-use tests result in
      increased testing.

PMID- 24335743
TI  - Human papillomavirus vaccine administration among Medicaid providers who
      consistently recommended vaccination.
AB  - We examined factors potentially related to providers' self-reported human
      papillomavirus vaccine administration to female Medicaid enrollees among
      providers who consistently recommended vaccination. Some pronounced variability
      was observed in characteristics among providers who consistently administered
      vaccination, including provider age, race, and Vaccines for Children enrollment;
      patient/parent vaccine refusal; patient race/ethnicity; and patient volume. 

PMID- 24335744
TI  - Suspected heterosexual transmission of bacterial vaginosis without seminal fluid
      exposure.
AB  - This report describes a case of suspected heterosexual transmission of bacterial
      vaginosis to a woman from a male partner who had undergone a radical
      prostatectomy. The most likely method of transmission in this case was through
      contact with infected desquamated epithelial cells from the male partner's distal
      urethra or coronal sulcus. 

PMID- 24335745
TI  - Use of first-line treatment for Neisseria gonorrhoeae after treatment guideline
      changes.
AB  - After 2 notices with treatment recommendation changes for Neisseria gonorrhoeae,
      the Philadelphia Department of Public Health documented medical therapy for 92%
      (3279/3551) of cases; 3001 (92%) received a recommended therapy. Nonrecommended
      therapies were documented in 8% of cases. Providers diagnosing 2 or less N.
      gonorrhoeae cases were more likely to use nonrecommended therapy. 

PMID- 24335746
TI  - Trends in receipt of sexually transmitted disease services among women 15 to 44
      years old in the United States, 2002 to 2006-2010.
AB  - BACKGROUND: To describe recent trends in the receipt of sexually transmitted
      disease (STD) services among women (age, 15-44 years) from 2002 to 2006-2010
      using the National Survey of Family Growth. METHODS: We analyzed trends in
      demographics, health insurance, and visit-related variables of women reporting
      receipt of STD services (counseling, testing, or treatment) in the past 12
      months. We also analyzed trends in the source of STD services and the payment
      method used. RESULTS: Receipt of STD services reported by women in the past 12
      months increased from 2002 (12.6%) to 2006-2010 (16.0%; P < 0.001). Receipt of
      services did not increase among adolescents (P = 0.592). Among women receiving
      STD services from a private doctor/HMO, the percentage with private insurance
      decreased over time (74.6%-66.8%), whereas the percentage with Medicaid increased
      (12.8%-19.7%; P = 0.020). For women receiving STD services at a public clinic or
      nonprimary care facility, there were no statistically significant differences by
      demographics, except that fewer adolescents but more young adults reported using
      a public clinic over time (P = 0.038). Among women who reported using Medicaid as
      payment, receipt of STD services at a public clinic significantly decreased
      (36.8%-25.4%; P = 0.019). For women who paid for STD services with private
      insurance, the only significant difference was an increase in having a copay over
      time (61.3%-70.1%; P = 0.012). CONCLUSIONS: Despite a significant increase in
      receipt of STD services over time, many women at risk for STDs did not receive
      services including adolescents. In addition, we identified important shifts in
      payment methods during this time frame.

PMID- 24335747
TI  - Novel whole-tissue quantitative assay of nitric oxide levels in Drosophila
      neuroinflammatory response.
AB  - Neuroinflammation is a complex innate immune response vital to the healthy
      function of the central nervous system (CNS). Under normal conditions, an
      intricate network of inducers, detectors, and activators rapidly responds to
      neuron damage, infection or other immune infractions. This inflammation of immune
      cells is intimately associated with the pathology of neurodegenerative disorders,
      such as Parkinson's disease (PD), Alzheimer's disease and ALS. Under compromised
      disease states, chronic inflammation, intended to minimize neuron damage, may
      lead to an over-excitation of the immune cells, ultimately resulting in the
      exacerbation of disease progression. For example, loss of dopaminergic neurons in
      the midbrain, a hallmark of PD, is accelerated by the excessive activation of the
      inflammatory response. Though the cause of PD is largely unknown, exposure to
      environmental toxins has been implicated in the onset of sporadic cases. The
      herbicide paraquat, for example, has been shown to induce Parkinsonian-like
      pathology in several animal models, including Drosophila melanogaster. Here, we
      have used the conserved innate immune response in Drosophila to develop an assay
      capable of detecting varying levels of nitric oxide, a cell-signaling molecule
      critical to the activation of the inflammatory response cascade and targeted
      neuron death. Using paraquat-induced neuronal damage, we assess the impact of
      these immune insults on neuroinflammatory stimulation through the use of a novel,
      quantitative assay. Whole brains are fully extracted from flies either exposed to
      neurotoxins or of genotypes that elevate susceptibility to neurodegeneration then
      incubated in cell-culture media. Then, using the principles of the Griess reagent
      reaction, we are able to detect minor changes in the secretion of nitric oxide
      into cell-culture media, essentially creating a primary live-tissue model in a
      simple procedure. The utility of this model is amplified by the robust genetic
      and molecular complexity of Drosophila melanogaster, and this assay can be
      modified to be applicable to other Drosophila tissues or even other small, whole
      organism inflammation models. 

PMID- 24335749
TI  - Tranexamic acid impairs gamma-aminobutyric acid receptor type A-mediated synaptic
      transmission in the murine amygdala: a potential mechanism for drug-induced
      seizures?
AB  - BACKGROUND: Tranexamic acid (TXA) is commonly used to reduce blood loss in
      cardiac surgery and in trauma patients. High-dose application of TXA is
      associated with an increased risk of postoperative seizures. The neuronal
      mechanisms underlying this proconvulsant action of TXA are not fully understood.
      In this study, the authors investigated the effects of TXA on neuronal
      excitability and synaptic transmission in the basolateral amygdala. METHODS:
      Patch clamp recordings and voltage-sensitive dye imaging were performed in acute
      murine brain slices. Currents through N-methyl-D-aspartate, alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid, and gamma-aminobutyric acid receptor type A
      (GABAA) receptors were recorded. GABAA receptor-mediated currents were evoked
      upon electrical stimulation or upon photolysis of caged GABA. TXA was applied at
      different concentrations. RESULTS: Voltage-sensitive dye imaging demonstrates
      that TXA (1 mM) reversibly enhances propagation of neuronal excitation (mean +/-
      SEM, 129 +/- 6% of control; n = 5). TXA at concentrations of 0.1, 0.3, 1, 5, or
      10 mM led to a dose-dependent reduction of GABAA receptor-mediated currents in
      patch clamp recordings. There was no difference in the half-maximal inhibitory
      concentration for electrically (0.76 mM) and photolytically (0.84 mM) evoked
      currents (n = 5 to 9 for each concentration), and TXA did not affect the paired
      pulse ratio of GABAA receptor-mediated currents. TXA did not impact glutamatergic
      synaptic transmission. CONCLUSIONS: This study clearly demonstrates that TXA
      enhances neuronal excitation by antagonizing inhibitory GABAergic
      neurotransmission. The results provide evidence that this effect is mediated via
      postsynaptic mechanisms. Because GABAA receptor antagonists are known to promote
      epileptiform activity, this effect might explain the proconvulsant action of TXA.

PMID- 24335748
TI  - Psychometric validation of the Confidence in Performing Sexual Intercourse
      Questionnaire and Difficulty in Performing Sexual Intercourse Questionnaire.
AB  - The objective of this study was to perform psychometric testing of two new
      patient-reported outcome instruments (PROs), the Confidence in Performing Sexual
      Intercourse Questionnaire (CPSIQ) and the Difficulty in Performing Sexual
      Intercourse Questionnaire (DPSIQ). The new PROs were administered at non-drug,
      run-in, baseline and end point in men with erectile dysfunction (ED)
      participating in a randomized clinical trial of ED treatment (Study 1, n=291) and
      two times within 2 weeks to men with ED participating in a web-based survey
      (Study 2, n=71). Psychometric tests included factor analysis, internal
      consistency and test-retest reliability, construct validity and responsiveness.
      Analysis of data from Study 1 participants (74% <=65 years, 83% Caucasian and 75%
      with moderate ED) suggested one-factor solutions for both PROs with Cronbach's
      alpha >0.88. CPSIQ and DPSIQ total scores discriminated between ED severity
      groups showed worsening after a 4-week non-drug, run-in period, and showed
      improvement after 12 weeks of ED treatment (all, P<0.05). Intraclass correlation
      coefficients calculated for the CPSIQ and DPSIQ, using data from Study 2
      participants (82% <=65 years, 90% Caucasian and 66% with mild ED), were 0.56 and
      0.83, respectively. The CPSIQ and DPSIQ show potential for augmenting existing
      treatment outcome measures used in the evaluation of ED treatment. 

PMID- 24335750
TI  - Handheld Doppler to improve pulse checks during resuscitation of putative
      pulseless electrical activity arrest.

PMID- 24335751
TI  - An angular fluidic channel for prism-free surface-plasmon-assisted fluorescence
      capturing.
AB  - Surface plasmon excitation provides stronger enhancement of the fluorescence
      intensity and better sensitivity than other sensing approaches but requires
      optimal positioning of a prism to ensure optimum output of the incident light.
      Here we describe a simple, highly sensitive optical sensing system combining
      surface plasmon excitation and fluorescence to address this limitation. V-shaped
      fluidic channels are employed to mimic the functions of a prism, sensing plate,
      and flow channel in a single setup. Superior performance is demonstrated for
      different biomolecular recognition reactions on a self-assembled monolayer, and
      the sensitivity reaches 100 fM for biotin-streptavidin interactions. Using an
      antibody as a probe, we demonstrate the detection of intact influenza viruses at
      0.2 HA units ml-1 levels. The convenient sensing system developed here has the
      advantages of being prism-free and requiring less sample (1-2 MUl), making this
      platform suitable for use in situations requiring low sample volumes.

PMID- 24335752
TI  - Downregulation of reversion-inducing cysteine-rich protein with Kazal motifs in
      malignant melanoma: inverse correlation with membrane-type 1-matrix
      metalloproteinase and tissue inhibitor of metalloproteinase 2.
AB  - The invasive phenotype of many tumors is associated with an imbalance between the
      matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of
      metalloproteinases (TIMPs), and the membrane-anchored reversion-inducing cysteine
      rich protein with Kazal motifs (RECK). RECK inhibits MMP-2, MMP-9, and MT1-MMP,
      and has been linked to patient survival and better prognosis in several types of
      tumors. However, despite the wide implication of these MMPs in melanoma
      establishment and progression, the role of RECK in this type of tumor is still
      unknown. Here, we analyzed the expression of RECK, TIMP1, TIMP2, TIMP3, MT1MMP,
      MMP2, and MMP9 in two publicly available melanoma microarray datasets and in a
      panel of human melanoma cell lines. We found that RECK is downregulated in
      malignant melanoma, accompanied by upregulation of MT1MMP and TIMP2. In both
      datasets, we observed that the group of samples displaying higher RECK levels
      show lower median expression levels of MT1MMP and TIMP2 and higher levels of
      TIMP3. When tested in a sample-wise manner, these correlations were statistically
      significant. Inverse correlations between RECK, MT1MMP, and TIMP2 were verified
      in a panel of human melanoma cell lines and in a further reduced model that
      includes a pair of matched primary tumor-derived and metastasis-derived cell
      lines. Taken together, our data indicate a consistent correlation between RECK,
      MT1MMP, and TIMP2 across different models of clinical samples and cell lines and
      suggest evidence of the potential use of this subset of genes as a gene signature
      for diagnosing melanoma. 

PMID- 24335753
TI  - An extract of Rhodobacter sphaeroides reduces cisplatin-induced nephrotoxicity in
      mice.
AB  - Cisplatin is used as a treatment for various types of solid tumors. Renal injury
      severely limits the use of cisplatin. Renal cell apoptosis, oxidative stress, and
      inflammation contribute to cisplatin-induced nephrotoxicity. Previously, we found
      that an extract of Rhodobacter sphaeroides (LycogenTM) inhibited proinflammatory
      cytokines and the production of nitric oxide in activated macrophages in a
      dextran sodium sulfate (DSS)-induced colitis model. Here, we evaluated the effect
      of LycogenTM, a potent anti-inflammatory agent, in mice with cisplatin-induced
      renal injury. We found that attenuated renal injury correlated with decreased
      apoptosis due to a reduction in caspase-3 expression in renal cells. Oral
      administration of LycogenTM significantly reduced the expression of tumor
      necrosis factor-alpha and interleukin-1beta in mice with renal injury. LycogenTM
      reduces renal dysfunction in mice with cisplatin-induced renal injury. The
      protective effects of the treatment included blockage of the cisplatin-induced
      elevation in serum urea nitrogen and creatinine. Meanwhile, LycogenTM attenuated
      body weight loss and significantly prolonged the survival of mice with renal
      injury. We propose that LycogenTM exerts anti-inflammatory activities that
      represent a promising strategy for the treatment of cisplatin-induced renal
      injury. 

PMID- 24335755
TI  - 'Gay bowel syndrome': relic or real (and returning) phenomenon?
AB  - PURPOSE OF REVIEW: This article aims to review the term 'gay bowel syndrome',
      including the recent research looking at increased rates of bowel infections in
      men who have sex with men (MSM), particularly in light of the recent Shigella
      outbreaks in MSM in London and New York, and considers whether 'gay bowel
      syndrome' is a syndrome that really exists and is worthy of further research and
      specific treatment, or whether the term continues to be obsolete and not useful.
      RECENT FINDINGS: Little or no recent research exists around the concept of a
      specific syndrome affecting the bowels of MSM. Rather, there seems to be a
      clustering of diseases in certain high-risk groups, especially those in urban
      areas with multiple sexual partners, recreational drug use, and possible
      concomitant HIV infection. SUMMARY: All healthcare practitioners (including non
      sexual health/HIV specialists) need to consider careful and thorough history
      taking (including sexual history) to identify those at risk.

PMID- 24335754
TI  - Biotoxin detection using cell-based sensors.
AB  - Cell-based biosensors (CBBs) utilize the principles of cell-based assays (CBAs)
      by employing living cells for detection of different analytes from environment,
      food, clinical, or other sources. For toxin detection, CBBs are emerging as
      unique alternatives to other analytical methods. The main advantage of using CBBs
      for probing biotoxins and toxic agents is that CBBs respond to the toxic
      exposures in the manner related to actual physiologic responses of the vulnerable
      subjects. The results obtained from CBBs are based on the toxin-cell
      interactions, and therefore, reveal functional information (such as mode of
      action, toxic potency, bioavailability, target tissue or organ, etc.) about the
      toxin. CBBs incorporate both prokaryotic (bacteria) and eukaryotic (yeast,
      invertebrate and vertebrate) cells. To create CBB devices, living cells are
      directly integrated onto the biosensor platform. The sensors report the cellular
      responses upon exposures to toxins and the resulting cellular signals are
      transduced by secondary transducers generating optical or electrical signals
      outputs followed by appropriate read-outs. Examples of the layout and operation
      of cellular biosensors for detection of selected biotoxins are summarized. 

PMID- 24335756
TI  - Transcriptome dynamics and diversity in the early zebrafish embryo.
AB  - Recent years advances in high-throughput sequencing have improved our
      understanding of how transcripts regulate early vertebrate development. Here, we
      review the transcriptome dynamics and diversity during early stages of zebrafish
      embryogenesis. Transcriptome dynamics is characterized by different patterns of
      mRNA degradation, activation of dormant transcripts and onset of transcription.
      Several studies have shown a striking diversity of both coding and non-coding
      transcripts. However, in the aftermath of this immense increase in data,
      functional studies of both protein-coding and non-coding transcripts are lagging
      behind. We anticipate that the forthcoming years will see studies relying on
      different high-throughput sequencing technologies and genomic tools developed for
      zebrafish embryos to further pin down yet un-annotated transcript-function
      relationships. 

PMID- 24335757
TI  - Epigenomics and the concept of degeneracy in biological systems.
AB  - Researchers in the field of epigenomics are developing more nuanced
      understandings of biological complexity, and exploring the multiple pathways that
      lead to phenotypic expression. The concept of degeneracy-referring to the
      multiple pathways that a system recruits to achieve functional plasticity-is an
      important conceptual accompaniment to the growing body of knowledge in
      epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy
      refers to the plasticity of traits whose function overlaps in some environments,
      but diverges in others. While a redundant system is composed of repeated
      identical elements performing the same function, a degenerate system is composed
      of different elements performing similar or overlapping functions. Here, we
      describe the degenerate structure of gene regulatory systems from the basic
      genetic code to flexible epigenomic modifications, and discuss how these
      structural features have contributed to organism complexity, robustness,
      plasticity and evolvability. 

PMID- 24335758
TI  - Quantitative analysis and characterization of atherosclerotic lesions in the
      murine aortic sinus.
AB  - Atherosclerosis is a disease of the large arteries and a major underlying cause
      of myocardial infarction and stroke. Several different mouse models have been
      developed to facilitate the study of the molecular and cellular pathophysiology
      of this disease. In this manuscript we describe specific techniques for the
      quantification and characterization of atherosclerotic lesions in the murine
      aortic sinus and ascending aorta. The advantage of this procedure is that it
      provides an accurate measurement of the cross-sectional area and total volume of
      the lesion, which can be used to compare atherosclerotic progression across
      different treatment groups. This is possible through the use of the valve
      leaflets as an anatomical landmark, together with careful adjustment of the
      sectioning angle. We also describe basic staining methods that can be used to
      begin to characterize atherosclerotic progression. These can be further modified
      to investigate antigens of specific interest to the researcher. The described
      techniques are generally applicable to a wide variety of existing and newly
      created dietary and genetically-induced models of atherogenesis. 

PMID- 24335759
TI  - Actual developments in European regulatory and health technology assessment of
      new cancer drugs: what does this mean for oncology in Europe?

PMID- 24335761
TI  - Co-operativity in a nanocrystalline solid-state transition.
AB  - Co-operativity is a remarkable phenomenon mostly seen in biology, where initial
      reaction events significantly alter the propensity of subsequent reaction events,
      giving rise to a nonlinear tightly regulated synergistic response. Here we have
      found unique evidence of atomic level co-operativity in an inorganic material. A
      thousand-atom nanocrystal (NC) of the inorganic solid cadmium selenide exhibits
      strong positive co-operativity in its reaction with copper ions. A NC doped with
      a few copper impurities becomes highly prone to be doped even further, driving an
      abrupt transition of the entire NC to the copper selenide phase, as manifested by
      a strongly sigmoidal response in optical spectroscopy and electron diffraction
      measurements. The examples presented here suggest that cooperative phenomena may
      have an important role in the solid state, especially in the nucleation of new
      chemical phases, crystal growth, and other materials' transformations. 

PMID- 24335760
TI  - A practical limited sampling strategy to predict free prednisolone exposure and
      glycemia in kidney transplant recipients.
AB  - BACKGROUND: Despite significant interindividual variability in prednisolone
      pharmacokinetics and potentially serious consequences with inadequate or
      excessive exposure, monitoring of prednisolone levels is not employed to guide
      therapy. As ultrahigh-performance liquid chromatography-tandem mass spectrometry
      methods can now measure the active free fraction of prednisolone, this study
      aimed to evaluate the performance of 15 published limited sampling strategies
      (LSSs) for predicting free prednisolone exposure in adult kidney transplant
      recipients and to examine the relationship between free/total prednisolone
      exposure and plasma glucose. METHODS: The study was performed in 11 subjects
      without diabetes 3-4 weeks postkidney transplantation. Area under the
      concentration time curve profiles of total and free prednisolone from 0 to 12
      hours postdose (AUC0-12) were determined and compared with predicted AUC0-12
      values calculated from published LSSs. Venous glucose was measured concurrently
      with the 13 sampling time points. RESULTS: The mean (+/-SD) age of subjects was
      52 +/- 12 years, 5 were men and the median (interquartile range) daily
      prednisolone dose was 20.0 mg (20.0-22.5). Interindividual variation in dose
      adjusted free and total prednisolone exposure was 1.9- and 3.2-fold,
      respectively. All 15 free prednisolone LSSs exhibited good correlation (r >=
      0.83), with bias and imprecision less than 15%. An LSS incorporating 1.25- and 3
      hour samples had the highest predictive power (r = 0.97, bias 1.2%, imprecision
      5.6%). Free prednisolone AUC0-12 correlated with peak glucose levels (r = 0.65, P
      = 0.037), as did predicted AUC0-12 from 14/15 LSSs. CONCLUSIONS: Biologically
      active free prednisolone exposure can be accurately predicted postkidney
      transplantation by LSSs incorporating 2-point concentration sampling. Peak plasma
      glucose concentration correlated well with prednisolone exposure.

PMID- 24335762
TI  - Ageing diminishes the modulation of human brain responses to visual food cues by
      meal ingestion.
AB  - BACKGROUND/OBJECTIVES: Rates of obesity are greatest in middle age. Obesity is
      associated with altered activity of brain networks sensing food-related stimuli
      and internal signals of energy balance, which modulate eating behaviour. The
      impact of healthy mid-life ageing on these processes has not been characterised.
      We therefore aimed to investigate changes in brain responses to food cues, and
      the modulatory effect of meal ingestion on such evoked neural activity, from
      young adulthood to middle age. SUBJECTS/METHODS: Twenty-four healthy, right
      handed subjects, aged 19.5-52.6 years, were studied on separate days after an
      overnight fast, randomly receiving 50 ml water or 554 kcal mixed meal before
      functional brain magnetic resonance imaging while viewing visual food cues.
      RESULTS: Across the group, meal ingestion reduced food cue-evoked activity of
      amygdala, putamen, insula and thalamus, and increased activity in precuneus and
      bilateral parietal cortex. Corrected for body mass index, ageing was associated
      with decreasing food cue-evoked activation of right dorsolateral prefrontal
      cortex (DLPFC) and precuneus, and increasing activation of left ventrolateral
      prefrontal cortex (VLPFC), bilateral temporal lobe and posterior cingulate in the
      fasted state. Ageing was also positively associated with the difference in food
      cue-evoked activation between fed and fasted states in the right DLPFC, bilateral
      amygdala and striatum, and negatively associated with that of the left
      orbitofrontal cortex and VLPFC, superior frontal gyrus, left middle and temporal
      gyri, posterior cingulate and precuneus. There was an overall tendency towards
      decreasing modulatory effects of prior meal ingestion on food cue-evoked regional
      brain activity with increasing age. CONCLUSIONS: Healthy ageing to middle age is
      associated with diminishing sensitivity to meal ingestion of visual food cue
      evoked activity in brain regions that represent the salience of food and direct
      food-associated behaviour. Reduced satiety sensing may have a role in the greater
      risk of obesity in middle age.

PMID- 24335763
TI  - Comparing decision making in average and overweight children and adolescents.
AB  - OBJECTIVE: The current study investigates the aspects of self-regulation skills
      in overweight and normal-weight children, which may be related to their
      overeating problems. It is hypothesised that overweight children may show poor
      decision-making behaviour, and this may be because of two processes:
      hypersensitivity to reward or future insensitivity. SUBJECTS: Average weight
      children (n=66) and overweight children (n=64) between 11 and 16 years were
      tested with the developmentally appropriate analogue of the Iowa gambling task.
      RESULTS: The results reveal that overweight children show decision-making failure
      ensued from future insensitivity. CONCLUSION: These findings provide support for
      the reward deficiency hypothesis or the anhedonic route to obesity in children.

PMID- 24335765
TI  - Spirituality and alcoholics anonymous.

PMID- 24335764
TI  - Kefir improves fatty liver syndrome by inhibiting the lipogenesis pathway in
      leptin-deficient ob/ob knockout mice.
AB  - OBJECTIVE: Fatty liver disease is commonly associated with obesity, insulin
      resistance and diabetes. Severe fatty liver is sometimes accompanied by
      steatohepatitis and may lead to the development of hepatocellular carcinoma. At
      present, there is no effective treatment for non-alcoholic fatty liver disease
      (NAFLD); thus, recent investigations have focused on developing effective
      therapeutics to treat this condition. This study aimed to evaluate the effects of
      kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to
      model fatty liver disease. RESULTS: In this study, we used leptin receptor
      deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice
      were orally administered the dairy product kefir (140 mg kg(-1) of body weight
      (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver
      syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum
      glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase
      (GPT) activities (P<0.05) and by decreasing the triglyceride (TG) and total
      cholesterol (TC) contents of the liver (P<0.05). Oral kefir administration also
      significantly reduced the macrovesicular fat quantity in liver tissue. In
      addition, kefir markedly decreased the expression of the genes sterol regulatory
      element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA
      carboxylase (ACC) (P<0.05) but not the expression of peroxisome proliferator
      activated receptor alpha (PPARalpha) or hepatic carnitine palmitoyltransferase
      1alpha (CPT1alpha) in the livers of ob/ob mice. CONCLUSION: On the basis of these
      results, we conclude that kefir improves NAFLD on BW, energy expenditure and
      basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may
      have the potential for clinical application to the prevention or treatment of
      NAFLD.

PMID- 24335766
TI  - Spirituality in addictions research: addressing prevention, treatment, and
      recovery.

PMID- 24335768
TI  - Relationship of spirituality or religion to recovery from substance abuse: a
      systematic review.
AB  - Spirituality and religion are frequently acknowledged as significant contributors
      to individuals' recovery from substance use disorders. This review focuses on the
      role that spirituality or religion plays in substance abuse treatment outcomes.
      Our search of three databases-PubMed, CINAHL, and Psych Info-turned up 29
      eligible studies for review. We group our findings according to whether the
      study's focus was on alcohol only or alcohol and other drug use. The most common
      treatment outcome was abstinence followed by treatment retention, alcohol or drug
      use severity, and discharge status. For most studies, we found evidence
      suggesting at least some support for a beneficial relationship between
      spirituality or religion and recovery from substance use disorders. Our review
      addresses the strengths and limitations of these studies.

PMID- 24335767
TI  - Spiritual awakening predicts improved drinking outcomes in a Polish treatment
      sample.
AB  - PURPOSE: This study examined concurrent and longitudinal associations between two
      dimensions of affiliation in Alcoholics Anonymous (AA)-attendance and spiritual
      awakening-and drinking outcomes among adult patients who were in treatment for
      alcohol dependence in Warsaw, Poland. In a study conducted at four addiction
      treatment centers, male and female patients (n = 118) with a DSM-IV diagnosis of
      alcohol dependence were assessed at baseline (Time 1 or T1), 1 month (T2), and 6
      12 months postbaseline (T3) for AA meeting attendance, various aspects of AA
      affiliation, and alcohol use. Alcoholics Anonymous meeting attendance and alcohol
      consumption were measured using the Timeline Followback interview. Self-report of
      having had a spiritual awakening was measured using a modified version of the
      Alcoholics Anonymous Involvement Scale. RESULTS: There were no cross-sectional or
      longitudinal associations between AA meeting attendance and improved drinking
      outcomes. In contrast, self-report of a spiritual awakening between T2 and T3 was
      significantly associated with abstinence (OR = 2.4, p < .05) and the absence of
      any heavy drinking (OR = 3.0, p < .05) at T3, even when demographic and clinical
      characteristics were statistically controlled. CONCLUSIONS: Self-reports of
      spiritual awakening predicted improved drinking outcomes in a Polish treatment
      sample.

PMID- 24335770
TI  - A historical review of perceptions of key aspects of spirituality and religion
      within alcoholics anonymous.
AB  - This historical research aimed to develop an accurate perception of the role of
      spirituality and religion within the history of Alcoholics Anonymous. Primary and
      secondary sources were reviewed. The study identified that Bill W. and Dr. Bob
      established the format for the support group based on the ideas of William James,
      which formed the base for the Oxford Groups. Alcoholics Anonymous was clearly
      viewed as a spiritual group and not a religion. The review also showed that the
      two founders had each experienced one of the two types of spiritual awakenings
      that James had addressed. These findings will help nurses clarify their own
      perceptions of this organization so they may accurately educate individuals who
      they are encouraging to participate in this program while recovering from an
      addiction.

PMID- 24335771
TI  - Came to believe: spirituality as a mechanism of change in alcoholics anonymous: a
      review of the literature from 1992 to 2012.
AB  - Over the last 20 years, there has been an increase in substance abuse research
      focusing on the efficacy of 12-step programs like Alcoholics Anonymous. Results
      indicate that AA reduces relapse risk and works as well as cognitive behavioral
      therapy and motivational interviewing in reducing the quantity and frequency of
      alcohol use. More recent studies have focused on identifying the mechanisms of
      behavior change at work in AA, especially the use of spiritual practices in the
      maintenance of sobriety. These findings are compared with the role of
      spirituality described in AA literature to expand the understanding of these
      processes in recovery from substance use disorders.

PMID- 24335772
TI  - Religiosity/spirituality and substance use in adolescence as related to positive
      development: a literature review.
AB  - Positive youth development interventions are strategies to address adolescent
      health risk behaviors and are recommended in Healthy People 2020. Although the
      incorporation of spirituality into these programs has been recommended, much of
      the empirical literature actually addresses religiosity rather than spirituality.
      The purpose of our review of 36 studies published between 2007 and 2013 was to
      (1) examine the relationship of religiosity and/or spirituality to substance use
      and abuse in adolescence, (2) discuss the measurement and meaning of the concept
      of spirituality in contrast to religiosity in adolescence, and (3) discuss the
      implications of these empirical studies for the concept of positive youth
      development. Findings from this literature review supported earlier findings of
      an inverse relationship between religiosity and substance use, a lack of or
      inconsistent definition of spirituality and religiosity as well as limited
      measures to address these constructs. Recommendations from this review include
      dedicated work by interdisciplinary teams to address consistency in definitions
      and creation of consistent tools that include consideration of the stages of
      development included in the adolescent years. From a research and clinical
      perspective, an interprofessional approach to clarify the concepts of
      spirituality and spiritual development would not only benefit research but could
      inform the substance abuse prevention field. This work is essential to insure
      that evidence-based strategies, which include religiosity and spirituality, are
      developed with the goal of protecting youth and supporting positive development
      of adolescents.

PMID- 24335775
TI  - An interview with Fran Ludwig, MS, RN, nurse educator.

PMID- 24335777
TI  - EYEE: exciting year for eyes and ears.

PMID- 24335779
TI  - West nile virus in the United States - a historical perspective.
AB  - Prior to 1999, West Nile virus (WNV) was a bit player in the screenplay of global
      vector-borne viral diseases. First discovered in the West Nile District of Uganda
      in 1937, this Culex sp.-transmitted virus was known for causing small human
      febrile outbreaks in Africa and the Middle East. Prior to 1995, the last major
      human WNV outbreak was in the 1950s in Israel. The epidemiology and ecology of
      WNV began to change in the mid-1990s when an epidemic of human encephalitis
      occurred in Romania. The introduction of WNV into Eastern Europe was readily
      explained by bird migration between Africa and Europe. The movement of WNV from
      Africa to Europe could not, however, predict its surprising jump across the
      Atlantic Ocean to New York City and the surrounding areas of the United States
      (U.S.). This movement of WNV from the Eastern to Western Hemisphere in 1999, and
      its subsequent dissemination throughout two continents in less than ten years is
      widely recognized as one of the most significant events in arbovirology during
      the last two centuries. This paper documents the early events of the introduction
      into and the spread of WNV in the Western Hemisphere. 

PMID- 24335780
TI  - Vascular endothelial growth factor levels in dobrava/belgrade virus infections.
AB  - The levels of vascular endothelial growth factor-A (VEGF) were estimated in 102
      serum samples from 63 hospitalized Greek patients with hemorrhagic fever with
      renal syndrome (HFRS) caused by Dobrava/Belgrade virus. Significantly higher VEGF
      levels were seen in the severe when compared with non-severe cases (mean values
      851.96 pg/mL and 326.75 pg/mL, respectively; p = 0.003), while a significant
      difference was observed among groups based on the day after the onset of illness.
      In both severe and non-severe cases, VEGF peaked in the second week of illness;
      however, elevation of VEGF in the severe cases started later and remained high
      until convalescence, suggesting that the role of VEGF was associated with repair
      of vascular damage rather than with increased permeability. 

PMID- 24335778
TI  - Phylogeographic diversity of pathogenic and non-pathogenic hantaviruses in
      slovenia.
AB  - Slovenia is a very diverse country from a natural geography point of view, with
      many different habitats within a relatively small area, in addition to major
      geological and climatic differences. It is therefore not surprising that several
      small mammal species have been confirmed to harbour hantaviruses: A. flavicollis
      (Dobrava virus), A. agrarius (Dobrava virus-Kurkino), M. glareolus (Puumala
      virus), S. areanus (Seewis virus),M. agrestis, M. arvalis and M. subterraneus
      (Tula virus). Three of the viruses, namely the Dobrava, Dobrava-Kurkino and
      Puumala viruses, cause disease in humans, with significant differences in the
      severity of symptoms. Due to changes in haemorrhagic fever with renal syndrome
      cases (HFRS) epidemiology, a detailed study on phylogenetic diversity and
      molecular epidemiology of pathogenic and non-pathogenic hantaviruses circulating
      in ecologically diverse endemic regions was performed. The study presents one of
      the largest collections of hantavirus L, M and S sequences obtained from hosts
      and patients within a single country. Several genetic lineages were determined
      for each hantavirus species, with higher diversity among non-pathogenic compared
      to pathogenic viruses. For pathogenic hantaviruses, a significant geographic
      clustering of human- and rodent-derived sequences was confirmed. Several
      geographic and ecological factors were recognized as influencing and limiting the
      formation of endemic areas. 

PMID- 24335781
TI  - Use of an eight-arm radial water maze to assess working and reference memory
      following neonatal brain injury.
AB  - Working and reference memory are commonly assessed using the land based radial
      arm maze. However, this paradigm requires pretraining, food deprivation, and may
      introduce scent cue confounds. The eight-arm radial water maze is designed to
      evaluate reference and working memory performance simultaneously by requiring
      subjects to use extra-maze cues to locate escape platforms and remedies the
      limitations observed in land based radial arm maze designs. Specifically,
      subjects are required to avoid the arms previously used for escape during each
      testing day (working memory) as well as avoid the fixed arms, which never contain
      escape platforms (reference memory). Re-entries into arms that have already been
      used for escape during a testing session (and thus the escape platform has been
      removed) and re-entries into reference memory arms are indicative of working
      memory deficits. Alternatively, first entries into reference memory arms are
      indicative of reference memory deficits. We used this maze to compare performance
      of rats with neonatal brain injury and sham controls following induction of
      hypoxia-ischemia and show significant deficits in both working and reference
      memory after eleven days of testing. This protocol could be easily modified to
      examine many other models of learning impairment. 

PMID- 24335782
TI  - Active vasodilation by sympathetic outflow to limb skin in a patient with
      progressive aphasia.
AB  - Despite considerable interest, a pure vasodilator response by skin sympathetic
      nerve activity (SSNA) bursts in human limbs has not been observed in previous
      studies. In a patient with progressive nonfluent aphasia, SSNA, sympathetic skin
      response, and skin blood flow were simultaneously recorded at rest and during
      electrical stimulation. There was a very low frequency of SSNA bursts at rest,
      and when electrical stimulation was delivered, reflex bursts of SSNA were always
      observed followed by a sympathetic skin response and an increase in skin blood
      flow. The reflex latency of SSNA was slightly prolonged and the mean amplitude of
      reflex SSNA bursts was lower after electrical stimulation, compared with the
      responses in healthy controls. We report for the first time that the active
      vasodilator component of cutaneous sympathetic activity in limbs was recorded
      without any vasoconstrictor component in a patient with progressive aphasia. 

PMID- 24335783
TI  - A systematic review of age, sex, ethnicity, and race as predictors of violent
      recidivism.
AB  - Recidivism of released prisoners, especially violent recidivism, is an important
      policy issue. Equally important is an understanding of how demographic risk
      factors may act as moderators of recidivism. Knowledge of such relationships is
      important in developing a deeper theoretical understanding of the risk of
      recidivism as well as identifying points of intervention that may need to be re
      oriented to reduce recidivism. The present study conducts a meta-analytic review
      of the violent recidivism literature focusing on the role of several demographic
      risk factors. Findings show that age, sex, and race (Whites) were significantly
      related to violent recidivism. Implications and directions for future research
      are identified. 

PMID- 24335784
TI  - Intervening to prevent repeat offending among moderate- to high-risk domestic
      violence offenders: a second-responder program for men.
AB  - Clear directions about best strategies to reduce recidivism among domestic
      violence offenders have remained elusive. The current study offers an initial
      evaluation of an RNR (Risk, Needs, and Responsivity)-focused second-responder
      program for men accused of assaulting their intimate partners and who were judged
      as being at moderate to high risk for re-offending. A quasi-experimental design
      was used to compare police outcomes for 40 men attending a second-responder
      intervention program to 40 men with equivalent levels of risk for re-offense who
      did not attend intervention (comparison group). Results showed that there were
      significant, substantial, and lasting differences across groups in all outcome
      domains. In terms of recidivism, rates of subsequent domestic-violence-related
      changes were more than double for men in the comparison group as compared with
      the intervention group in both 1-year (65.9% vs. 29.3%) and 2-year (41.5% vs.
      12.2%) follow-up. Changes in the rates of arrest were consistent with reductions
      in men's general involvement with police, with men in the intervention group
      receiving fewer charges for violent offenses, administrative offenses, and
      property offenses over the 2 years following intervention than men in the
      comparison group. Not surprisingly, these differences result in a much lower
      estimated amount of police time with intervention men than for comparison men.
      Results are discussed with reference to the possible impact of sharing
      information with men about their assessed risk for re-offending within a
      therapeutic justice context. 

PMID- 24335785
TI  - Ton That Tung's livers.
AB  - Born in the early 20th century, the Vietnamese surgeon Ton That Tung received his
      medical education in French colonial Indochina at the fledgling l'Ecole de
      Medecine de Hanoi, the first indigenous medical school in Southeast Asia. The
      benefactor of a postgraduate position at the medical school, Ton That Tung
      subsequently obtained his surgical training at the Phu Doan Hospital in Hanoi and
      concurrently developed a passion for the study of liver anatomy, pathology, and
      surgery. His contributions to an understanding of liver anatomy based on
      meticulous dissection of autopsy specimens antedated and rivaled later work by
      the famous Western anatomists Couinaud, Healey, Schroy, and others. Ton That
      Tung's contributions, however, were overshadowed by the intense national
      struggles of the Vietnamese to establish independent rule and self-governance
      from the French and by eventual alignment with eastern bloc Communist countries,
      thus isolating much of his work behind the "Iron Curtain" until well after the
      end of the Cold War. Nevertheless, Ton That Tung remains a pioneer in liver
      anatomy and liver surgery. His commitment to surgical science and, more
      importantly, to the Vietnamese people stands as a tribute to the tireless pursuit
      of his ideals. 

PMID- 24335786
TI  - Influence of cyclic loading on the fracture toughness and load bearing capacities
      of all-ceramic crowns.
AB  - The purpose of this study was to investigate how cyclic loading influenced the
      fracture toughness of hot-press lithium disilicate and zirconia core materials
      and whether there was an increase in the propensity for crown failure. Two types
      of all-ceramic crowns including the IPS e.max Press system (n=24) and the Lava
      zirconia system (n=24), were selected. Sectioned specimens were subjected to
      cyclic loading with the maximum magnitude of 200 N (R=0.1) until two million
      cycles. The material properties including Young's modulus (E) and hardness (H)
      and the fracture toughness (KIC) of the core materials were evaluated using
      indentation methods (n=12 each). The load-bearing capacities of the specimens
      were examined by means of monotonic load to fracture (n=12 each). It was found
      that the material properties, including E, H and KIC, of the two types of dental
      ceramics, were reduced. Statistical analysis indicated that there were no
      significant influences of fatigue loading on material properties E and H for both
      types of dental ceramics or KIC for zirconia, while for the IPS e.max Press core,
      KIC, which was parallel to the direction of the lithium disilicate crystals, was
      significantly reduced (P=0.001). A conclusion was drawn that zirconia possesses
      high mechanical reliability and sustainable capacity to resist fatigue loading,
      while fatigue loading remarkably degraded the anisotropic mechanical behaviour of
      hot-press lithium disilicate ceramics. 

PMID- 24335787
TI  - Compliance and tolerability of subcutaneous hepatitis B immunoglobulin self
      administration in liver transplant patients: a prospective, observational,
      multicenter study.
AB  - BACKGROUND: Subcutaneous self-administration of hepatitis B immunoglobulin (HBIg)
      prophylaxis is preferred by patients, but compliance with the assigned regimen in
      routine practice is undocumented. MATERIAL AND METHODS: A prospective,
      observational, 18-week, open-label, single-arm, multicenter study assessed
      compliance and tolerability in maintenance liver transplant patients self
      administering subcutaneous HBIg at home according to local practice. RESULTS:
      Sixty-one patients were analyzed (median follow-up 18 weeks, range 14.0-27.9
      weeks), with 961/1006 injections (95.5%) administered at home during the study.
      Other than in 4 patients, HBIg was prescribed for weekly administration (500
      IU/L, n=39; 1000 IU/L, n=18) at study entry. Eighteen patients (29.5%) were
      assigned a dose lower than recommended in the Summary of Product Characteristics.
      The primary variable of compliance failure, defined as >= 1 hepatitis B surface
      antibody (anti-HBs) serum trough level <100 IU/L, occurred in 4 patients (6.6%;
      95% CI 1.8%, 15.9%), 3 of whom were receiving a dose below that recommended for
      their body weight. Anti-HBs levels exceeded 100 IU/L in all patients at the final
      visit. Mean (SD) anti-HBs level at the first and final study visits was 248 (97)
      IU/L and 255 (104) IU/L, respectively. Patient compliance was graded good or very
      good by physicians in 91.8% of cases. No patients tested positive for HBsAg or
      HBV-DNA. Four patients experienced >= 1 adverse drug reactions, none of which was
      serious. No patient discontinued HBIg due to adverse events. CONCLUSIONS:
      Subcutaneous HBIg home-based self-administration under routine, real-life
      conditions is well-tolerated and associated with high compliance and maintaining
      protective anti-HBs serum concentration.

PMID- 24335788
TI  - A QTL model to map the common genetic basis for correlative phenotypic
      plasticity.
AB  - As an important mechanism for adaptation to heterogeneous environment, plastic
      responses of correlated traits to environmental alteration may also be
      genetically correlated, but less is known about the underlying genetic basis. We
      describe a statistical model for mapping specific quantitative trait loci (QTLs)
      that control the interrelationship of phenotypic plasticity between different
      traits. The model is constructed by a bivariate mixture setting, implemented with
      the EM algorithm to estimate the genetic effects of QTLs on correlative plastic
      response. We provide a series of procedure that test (1) how a QTL controls the
      phenotypic plasticity of a single trait; and (2) how the QTL determines the
      correlation of environment-induced changes of different traits. The model is
      readily extended to test how epistatic interactions among QTLs play a part in the
      correlations of different plastic traits. The model was validated through
      computer simulation and used to analyse multi-environment data of genetic mapping
      in winter wheat, showing its utilization in practice. 

PMID- 24335789
TI  - A year of progress.

PMID- 24335790
TI  - Can district nurses and care home staff improve bowel care for older people using
      a clinical benchmarking tool?
AB  - A quasi-experimental study tested a clinical benchmarking tool (Essence of Care)
      to improve bowel-related care for older people living in six care homes. In the
      intervention care homes, district nurses and care home staff used the clinical
      benchmarking tool to discuss and plan how to improve bowel care for residents. In
      the control care homes, staff were provided with detailed information about the
      residents and continence services contact details. The intervention was
      acceptable to care home and district nursing staff, and possible to incorporate
      into existing working patterns. The study did not demonstrate a significant
      reduction in bowel-related problems, although there was evidence in one care home
      of reduction in episodes of avoidable faecal incontinence. At an individual level
      of care, there were observable benefits, and examples of person-centred care were
      prompted through participating in the intervention and improved staff awareness.
      Clinical benchmarking tools can be used to structure discussion between district
      nurses and care home staff to review and plan care for residents. However, it
      takes time to achieve change and embedding this kind of approach requires either
      robust pre-existing working relationships or the involvement of a facilitator. 

PMID- 24335791
TI  - The importance of fixation and securing devices in supporting indwelling
      catheters.
AB  - Health-care professionals follow recognised national guidelines to assess
      clinical reasons for the insertion of urinary catheters. However, the use of
      fixation and securing devices is an area that is often neglected. Health-care
      professionals sometimes employ a 'do-it-yourself' approach, using adhesive tape
      or Velcro strapping devices, neither of which are appropriate. If urinary
      catheters are not secured appropriately, they can lead to severe trauma of a
      patient's urethra, potential damage to bladder neck, infection and inflammation,
      pain and irritation, possible bypassing, accidental dislodging of a catheter and
      a cleaving (condition whereby the catheter splits the penile or labial tissues).
      This article identifies reasons for using securing/fixation devices and explains
      the advantages and disadvantages of the different types of device in relation to
      individual patients. 

PMID- 24335792
TI  - Changing a urethral or suprapubic catheter: the patient's perspective.
AB  - Understanding the patient's perspective in any area of health care is now
      recognised as being crucial to good practice, but little is known about patients'
      views on living with an indwelling urinary catheter. In this study, 36 people
      living with either a urethral or suprapubic catheter across the UK were
      interviewed. After thematic analysis, the authors interpreted what they learned.
      Many issues were raised, including the need to know who was responsible for
      changing the catheter, the importance of continuity of care, 24-hour access to
      services, and good hygiene. Patients valued nurses with training and experience,
      with plenty of time, who took care and who listened to what mattered to the
      patient. The patient's perspective is important at all levels, not only when
      designing and planning an integrated continence service, but also in delivering
      services in the community.

PMID- 24335793
TI  - Early-onset dementia: the impact on family care-givers.
AB  - People with early-onset dementia (EOD) and their family carers remain an
      overlooked population within the policy and practice priorities of community
      health care. No standard provision of care or support currently exists for those
      with EOD and the family carer. Yet family members provide the majority of the
      full-time care required for this progressive, irreversible illness. The aim of
      this research was to explore the impact of care-giving on family members caring
      for a relative with EOD. The care-giving experiences identified in this study
      emphasise the need for improvement in the provision of community and specialised
      services for people with EOD and family carers. The key themes of this
      qualitative study were diagnostic problems, impact of care-giving, relationship
      change and lack of resources. These findings provide key directives for improving
      community practice, services and support for people with EOD and their family
      carers. 

PMID- 24335794
TI  - Mobility restriction and comorbidity in vision-impaired individuals living in the
      community.
AB  - A review of data presented in a national study of perceptions and experiences of
      mobility with an age-stratified sample of 564 Irish adults with vision impairment
      found that mobility was a significant issue. Comorbidity is a factor with 97
      (29.5%) of the under-65 age group and 135 (59%) of the older age group reporting
      additional health challenges. Adapting to vision loss and ageing has
      psychological, functional, social and health implications and help-seeking is a
      complex process. This may explain the limited use of mobility aids and guide dogs
      in the total sample (5%), with a notable absence of use in the older age group. A
      broad view of the Person-Environment-Occupation Model was proposed for primary
      and community care services, in collaboration with specialist vision impairment
      agencies to enhance mobility, maintain functional capacity, influence positive
      and healthy adaptation to vision impairment, social inclusion and quality of life
      in a population expected to increase by more than 170% over the next 25 years. 

PMID- 24335795
TI  - Lawfully withdrawing life-sustaining treatment.
AB  - The UK Supreme Court recently delivered its first judgement based on the
      application of the 2005 Mental Capacity Act. The plurality judgement given by
      Lady Hale clarified the law on medical futility and the circumstances under which
      a district nurse is lawfully able to withdraw life-sustaining treatment. It is
      essential that district nurses know when care and treatment becomes futile to
      ensure they are acting lawfully if a decision is taken to withdraw that care and
      treatment. This article considers the impact of the Supreme Court ruling on
      district nurse practice. 

PMID- 24335796
TI  - Putting a principle of palliative care into the community.

PMID- 24335797
TI  - Achieving an integrated care system.

PMID- 24335798
TI  - A very stable complex of a modified marine cyclopeptide with chloroform.
AB  - Noncovalent interactions play a pivotal role in molecular recognition. These
      interactions can be subdivided into hydrogen bonds, cation-pi interactions, ion
      pair interactions and London dispersion forces. The latter are considered to be
      weak molecular interactions and increase with the size of the interacting
      moieties. Here we show that even the small chloroform molecule forms a very
      stable complex with a modified marine cyclopeptide. By means of high-level
      quantum chemical calculations, the size of the dispersive interactions is
      calculated; the dispersion energy (approximately -40 kcal mol-1) is approximately
      as high as if the four outer atoms of the guest form four strong hydrogen bonds
      with the host. This strong binding of chloroform to a modified marine
      cyclopeptide allows the speculation that the azole-containing cyclopeptides
      haloform interaction may play some biological role in marine organisms such as
      algae.

PMID- 24335799
TI  - The cognitive neurology of the vestibular system.
AB  - PURPOSE OF REVIEW: The aim is to reappraise the current state about what we know
      of vestibular cognition. The review focuses on cognition and perception, and
      hence the stress on human studies. In addition, the cerebral cortex is the main
      but not exclusive brain region of interest. There is a brief mention of
      vestibular ocular function if only to demonstrate the differential processing
      between reflex and perception. The effect of vestibular activation on some
      aspects of cognition, for example neglect, is not reviewed, as there have been no
      recent landmark findings in this area. RECENT FINDINGS: The vestibular cerebellum
      is pivotal in the differential gating of vestibular perceptual and ocular signals
      to the cerebral cortex. The neuroanatomical correlates mediating vestibular
      sensations of self-motion ('am I moving?') and spatial orientation ('where am I
      now?') are distinct. Vestibular-motion perception is supported by a widespread
      white matter network. Vestibular activation specifically reduces visual motion
      cortical excitability, whereas other visual cortical regions show an increase in
      excitability. SUMMARY: As the vestibular ocular reflex (VOR) and self-motion
      perception can be uncoupled both behaviourally and in neural correlate, deficits
      underlying vestibular patients' symptoms may not be revealed by simple VOR
      assessment. Given the pivotal cerebellar role in gating vestibular signals to
      perceptual regions, modulating mechanisms of cerebellar plasticity, for example
      by combining training with medication or brain stimulation, may prove fruitful in
      treating the symptoms of chronic dizzy patients.

PMID- 24335800
TI  - The influence of anxiety on ocular motor control and gaze.
AB  - PURPOSE OF REVIEW: The influence of anxiety on ocular motor control and gaze has
      received less research attention than its effects on postural control and
      locomotion. This review summarizes research on trait anxiety, state anxiety,
      anxiety disorders, ocular motor reflexes, and gaze. It applies these findings to
      clinical problems of visually induced unsteadiness and dizziness (VUD, also known
      as visual vertigo), fear of falling (FoF), and chronic subjective dizziness
      (CSD). RECENT FINDINGS: Humans are inherently more sensitive to vertical heights
      than horizontal distances. Vertical height intolerance is reported by one-quarter
      to one-third of the general population. Humans also possess a gaze bias toward
      potentially threatening stimuli in the visual field, more prominent in
      individuals with higher versus lower trait anxiety and increased by state
      anxiety. This bias may drive hypervigilance-avoidance gaze patterns in patients
      with social anxiety disorder and specific phobias. Trait and state anxiety also
      appear to adversely affect gaze control, reducing gaze stability on visual
      targets. This may be one mechanism underlying persistent VUD and visual symptoms
      of CSD. Anxiety-related gaze diversion may increase gait instability in patients
      with FoF. SUMMARY: Anxiety affects ocular motor reflexes and gaze control in ways
      that may contribute to clinically significant visual and visual-vestibular
      syndromes.

PMID- 24335801
TI  - Role of alternative polyadenylation in epigenetic silencing and antisilencing.

PMID- 24335802
TI  - The antigen 43 structure reveals a molecular Velcro-like mechanism of
      autotransporter-mediated bacterial clumping.
AB  - Aggregation and biofilm formation are critical mechanisms for bacterial
      resistance to host immune factors and antibiotics. Autotransporter (AT) proteins,
      which represent the largest group of outer-membrane and secreted proteins in Gram
      negative bacteria, contribute significantly to these phenotypes. Despite their
      abundance and role in bacterial pathogenesis, most AT proteins have not been
      structurally characterized, and there is a paucity of detailed information with
      regard to their mode of action. Here we report the structure-function
      relationships of Antigen 43 (Ag43a), a prototypic self-associating AT protein
      from uropathogenic Escherichia coli. The functional domain of Ag43a displays a
      twisted L-shaped beta-helical structure firmly stabilized by a 3D hydrogen-bonded
      scaffold. Notably, the distinctive Ag43a L shape facilitates self-association and
      cell aggregation. Combining all our data, we define a molecular "Velcro-like"
      mechanism of AT-mediated bacterial clumping, which can be tailored to fit
      different bacterial lifestyles such as the formation of biofilms. 

PMID- 24335804
TI  - High curvature of the internal carotid artery is associated with the presence of
      intracranial aneurysms.
AB  - OBJECTIVE: Aneurysm formation in locations not involving vascular bifurcations
      has not been thoroughly analyzed. This study evaluated the relationship between
      the degree of vessel curvature and the presence of intracranial sidewall
      aneurysms of the internal carotid artery (ICA). METHODS: Catheter-based 3D
      rotational angiographic volumes and demographic data were available for 130 ICAs.
      Mean and peak curvatures were evaluated for the intracranial ICA (50 mm caudal
      from ICA bifurcation) and for its distal segment (from ICA bifurcation to carotid
      siphon). Four ICA groups, statistically matched for age, were identified: non
      aneurysmal women (n=33) and men (n=25), aneurysmal women (n=58) and men (n=14).
      Univariate and multivariate analyses were employed to evaluate statistical
      performance. RESULTS: Aneurysmal ICAs had significantly higher mean curvatures
      than non-aneurysmal ICAs in both the intracranial (p<0.001) and the distal ICA
      (p<0.001) for both genders. Peak curvature was significantly higher in aneurysmal
      versus non-aneurysmal men (p=0.008) but not in aneurysmal versus non-aneurysmal
      women (p=0.12). Mean curvature in non-aneurysmal ICAs was lower in men than in
      women but higher in aneurysmal ICAs in men than in women. In multivariate
      analysis, curvature was highly correlated with aneurysm presence but was
      independent of age, hypertension, hypercholesterolemia and smoking status.
      CONCLUSIONS: The presence of a sidewall aneurysm on the ICA is associated with
      high curvature in both genders. High curvature of the intracranial ICA, as well
      as of the distal segment, may indicate a higher risk for aneurysm formation. Non
      aneurysmal ICAs are less curved in men than in women, which may explain the
      gender predisposition to aneurysm formation.

PMID- 24335803
TI  - Cohesin and CTCF differentially affect chromatin architecture and gene expression
      in human cells.
AB  - Recent studies of genome-wide chromatin interactions have revealed that the human
      genome is partitioned into many self-associating topological domains. The
      boundary sequences between domains are enriched for binding sites of CTCC-binding
      factor (CTCF) and the cohesin complex, implicating these two factors in the
      establishment or maintenance of topological domains. To determine the role of
      cohesin and CTCF in higher-order chromatin architecture in human cells, we
      depleted the cohesin complex or CTCF and examined the consequences of loss of
      these factors on higher-order chromatin organization, as well as the
      transcriptome. We observed a general loss of local chromatin interactions upon
      disruption of cohesin, but the topological domains remain intact. However, we
      found that depletion of CTCF not only reduced intradomain interactions but also
      increased interdomain interactions. Furthermore, distinct groups of genes become
      misregulated upon depletion of cohesin and CTCF. Taken together, these
      observations suggest that CTCF and cohesin contribute differentially to chromatin
      organization and gene regulation. 

PMID- 24335805
TI  - Correlation of thrombus formation on 7 T MRI with histology in a rat carotid
      artery side wall aneurysm model.
AB  - BACKGROUND/PURPOSE: Various aneurysm animal models have been utilized to study
      the histological reaction post coil embolization. Our aim was to evaluate the
      imaging findings at day 14 of a rat external carotid artery side wall aneurysm
      treated with coil embolization using a gradient echo sequence on 7 T MRI and to
      correlate this with the histological findings. MATERIALS AND METHODS: Male
      Sprague Drawley rats were utilized to create a sidewall external carotid artery
      blind pouch aneurysm. A 5 mm segment of hydrocoil or bare platinum coil was
      inserted into the created aneurysm. Five sham operated rats were used as
      controls. The arterial construct was harvested on day 14. The block of tissue was
      evaluated with histopathology and immunohistochemistry. Prior to sacrifice, the
      animal underwent 7 T MRI. Statistical analysis was then performed to assess the
      correlation of signal abnormality with intra-aneurysmal thrombus formation on
      histology. RESULTS: 10 rats were used for the experiment. Five rats had
      implantation of hydrocoils and five of bare platinum coils. There was a
      statistically significant linear correlation between the intra-aneurysmal
      thrombus on histology and gradient echo 7 T MRI sequences. There was no
      correlation demonstrated in the hydrocoil implanted group. No thrombus or
      abnormal signal was seen in the sham group. CONCLUSIONS: In our experiment,
      thrombus formation in aneurysms treated with bare platinum coils is well
      correlated with the presence of abnormal signal on 7 T MRI at 14 days. No
      correlation was appreciated in the hydrocoil implanted group due to the presence
      of intra-aneurysmal reactive tissue instead of thrombus.

PMID- 24335806
TI  - Flow diverter assisted coil embolization of a very small ruptured ophthalmic
      artery aneurysm.
AB  - Small ruptured aneurysms present a unique problem to endovascular therapy. We
      report a case in which a patient presented with subarachnoid hemorrhage and a
      very small ruptured ophthalmic artery aneurysm, for which endovascular therapy
      was preferred secondary to severe cardiac comorbidities. Due to the aneurysm
      size, a small 1.5 mm coil was needed, but presented a significant risk of
      migration. Conventional stent assisted coiling was considered suboptimal as the
      small coil could have easily migrated through the strut. We present a novel
      technique of flow diverter assisted coil embolization in which a coil was placed
      within the aneurysm and a pipeline embolization device was then partially
      deployed, jailing the microcatheter and coil mass. Once in place, the coil was
      detached, securing the aneurysm, and preventing coil migration. Through the use
      of a flow diverter, some degree of aneurysm protection would still be expected in
      the event of coil migration toward the ophthalmic artery origin. 

PMID- 24335807
TI  - Identifying protein-protein interaction in Drosophila adult heads by Tandem
      Affinity Purification (TAP).
AB  - Genetic screens conducted using Drosophila melanogaster (fruit fly) have made
      numerous milestone discoveries in the advance of biological sciences. However,
      the use of biochemical screens aimed at extending the knowledge gained from
      genetic analysis was explored only recently. Here we describe a method to purify
      the protein complex that associates with any protein of interest from adult fly
      heads. This method takes advantage of the Drosophila GAL4/UAS system to express a
      bait protein fused with a Tandem Affinity Purification (TAP) tag in fly neurons
      in vivo, and then implements two rounds of purification using a TAP procedure
      similar to the one originally established in yeast(1) to purify the interacting
      protein complex. At the end of this procedure, a mixture of multiple protein
      complexes is obtained whose molecular identities can be determined by mass
      spectrometry. Validation of the candidate proteins will benefit from the resource
      and ease of performing loss-of-function studies in flies. Similar approaches can
      be applied to other fly tissues. We believe that the combination of genetic
      manipulations and this proteomic approach in the fly model system holds
      tremendous potential for tackling fundamental problems in the field of
      neurobiology and beyond. 

PMID- 24335808
TI  - Rosiglitazone: a case of regulatory hubris.

PMID- 24335809
TI  - A fifth of lung cancers detected by low dose CT screening are likely to be
      indolent, study says.

PMID- 24335810
TI  - More doctors are raising concerns with GMC about colleagues, MPs hear.

PMID- 24335811
TI  - Surgeon is suspended because of concerns over eight "avoidable" deaths.

PMID- 24335812
TI  - Tracking and sustaining improvement initiatives: leveraging quality dashboards to
      lead change in a neurosurgical department.
AB  - Increasingly, hospitals and physicians are becoming acquainted with business
      intelligence strategies and tools to improve quality of care. In 2007, the
      University of California Los Angeles (UCLA) Department of Neurosurgery created a
      quality dashboard to help manage process measures and outcomes and ultimately to
      enhance clinical performance and patient care. At that time, the dashboard was in
      a platform that required data to be entered manually. It was then reviewed
      monthly to allow the department to make informed decisions. In 2009, the
      department leadership worked with the UCLA Medical Center to align mutual quality
      improvement priorities. The content of the dashboard was redesigned to include 3
      areas of priorities: quality and safety, patient satisfaction, and efficiency and
      use. Throughout time, the neurosurgery quality dashboard has been recognized for
      its clarity and its success in helping management direct improvement strategies
      and monitor impact. We describe the creation and design of the neurosurgery
      quality dashboard at UCLA, summarize the evolution of its assembly process, and
      illustrate how it can be used as a powerful tool of improvement and change. The
      potential challenges and future directions of this business intelligence tool are
      also discussed.

PMID- 24335813
TI  - Practical clinical use of dynamic susceptibility contrast magnetic resonance
      imaging for the surgical treatment of moyamoya disease.
AB  - BACKGROUND: Precise evaluation of hemodynamic stress is important for the
      treatment of moyamoya disease (MMD). OBJECTIVE: To explore whether dynamic
      susceptibility contrast magnetic resonance imaging could predict the effects and
      risk of indirect bypass surgery on MMD. METHODS: Clinical data of patients with
      MMD who were evaluated preoperatively and postoperatively with dynamic
      susceptibility contrast magnetic resonance imaging and digital subtraction
      angiography were evaluated retrospectively. Indirect bypass surgery was performed
      on 115 hemispheres of 69 patients (mean age, 15 years; range, 3-54 years). We
      examined the correlations of ischemic events and revascularization with the mean
      transit time (MTT) delay to cerebellum. RESULTS: The hemispheres that caused the
      ischemic events (responsible hemisphere) had a significantly longer preoperative
      MTT delay than the nonresponsible hemispheres (2.66 +/- 1.34 vs 1.57 +/- 1.09
      seconds). The postoperative MTT delay fell significantly in the patients whose
      symptoms disappeared (preoperative, 2.61 +/- 1.35 seconds; postoperative, 1.35 +/
      0.96 seconds). Perioperative infarction occurred in 4 hemispheres (3.5%), and
      the MTT delay was significantly longer in those hemispheres than in the others
      (3.97 +/- 1.20 vs 2.38 +/- 1.34 seconds). The MTT delay was significantly longer
      in patients with higher angiographic stages. Indirect bypass surgery ameliorated
      the MTT delay to the same degree in adults and children. Digital subtraction
      angiography revealed that the induced revascularization was far superior in areas
      with longer MTT delays. CONCLUSION: Dynamic susceptibility contrast magnetic
      resonance imaging proved to be a useful clinical imaging method for patients with
      MMD. It may be helpful for selecting candidates for MMD intervention and for
      predicting the effects and risks of surgery. ABBREVIATIONS: DSC-MRI, dynamic
      susceptibility contrast magnetic resonance imagingMMD, moyamoya diseaseMTT, mean
      transit timeROI, region of interest.

PMID- 24335814
TI  - Intravenous tissue-type plasminogen activator therapy is an independent risk
      factor for symptomatic intracerebral hemorrhage after carotid endarterectomy.
AB  - BACKGROUND: Carotid endarterectomy (CEA) for symptomatic carotid artery stenosis
      and intravenous tissue-type plasminogen activator (IV-tPA) for acute ischemic
      stroke are proven therapies; however, the safety of CEA in stroke patients who
      recently received IV-tPA has not been established. OBJECTIVE: To evaluate the
      safety of CEA in stroke patients who recently received IV-tPA. METHODS: A
      retrospective review of patients who underwent CEA for symptomatic carotid artery
      stenosis was performed. The primary end point was postoperative symptomatic
      intracerebral hemorrhage (sICH). A univariate analysis of potential risk factors
      for sICH, including IV-tPA therapy, timing of CEA, degree of stenosis, and stroke
      severity, was performed. Factors with a value of P < .1 on univariate analysis
      were tested further. RESULTS: Among 142 patients, 3 suffered sICH after CEA: 2 of
      11 patients treated with IV-tPA (18.2%) and 1 of 131 patients not treated with IV
      tPA (0.8%). Both IV-tPA patients suffering sICH underwent CEA within 3 days of
      tPA administration. On univariate analysis, IV-tPA (P = .02), female sex (P =
      .09), shorter time between ischemic event and CEA (P = .06), and lower mean
      arterial pressure during the first 48 hours of admission (P = .08) were
      identified as risk factors for sICH. On multivariate analysis, IV-tPA was the
      only significant risk factor (P = .002 by stepwise logistic regression; P = .03
      by nominal logistic regression). CONCLUSION: This study indicates that IV-tPA is
      an independent risk factor for sICH after CEA. This suggests that CEA should be
      pursued cautiously in patients who recently received IV-tPA. Early surgery may be
      associated with an increased risk for sICH. ABBREVIATIONS: CEA, carotid
      endarterectomyIV-tPA, intravenous recombinant tissue-type plasminogen
      activatorMAP, mean arterial pressureNASCET, North American Symptomatic Carotid
      Endarterectomy TrialNIHSS, National Institutes of Health Stroke ScaleNINDS,
      National Institute of Neurological Disorders and StrokesICH, symptomatic
      intracerebral hemorrhageTIA, transient ischemic attack.

PMID- 24335815
TI  - Percutaneous stereotactic radiofrequency lesioning for trigeminal neuralgia:
      determination of minimum clinically important difference in pain improvement for
      patient-reported outcomes.
AB  - BACKGROUND: The Visual Analog Scale (VAS) and the Barrow Neurological Institute
      Pain Scale (BNI-PS) are 2 patient-reported outcome (PRO) tools frequently used to
      rate pain from trigeminal neuralgia (TN). Outcomes studies often use these
      patient-reported outcomes to assess treatment effectiveness, but it is unknown
      exactly what degree of change in the numerical scores constitutes the minimum
      clinically important difference (MCID). MCID remains uninvestigated for
      percutaneous stereotactic radiofrequency lesioning (RFL), a common surgical
      procedure for TN. OBJECTIVE: To determine MCID values for the VAS and BNI-PS in
      patients undergoing RFL. METHODS: Forty-three consecutive patients with TN who
      underwent RFL by a single surgeon were prospectively assessed with the VAS and
      BNI-PS preoperatively and 3 years postoperatively. Three anchors were used to
      assign each patient's outcome: satisfaction, willingness to have the surgery
      again, and Health Transition Index. We then used 3 well-established, anchor-based
      methods to calculate MCID: average change, minimum detectable change, and change
      difference. RESULTS: Patients experienced substantial improvement in both VAS
      (9.81 vs 3.35; P < .001) and BNI-PS (4.95 vs 2.44; P < .001) after RFL. The 3
      MCID calculation methods generated a range of MCID values for each of the PROs
      (VAS, 4.13-8.20; BNI-PS, 1.03-3.30). The area under the receiver-operating
      characteristic curve was greater for BNI-PS compared with VAS for all 3 anchors,
      indicating that BNI-PS is probably better suited for calculating MCID.
      CONCLUSION: RFL-specific MCID is variable on the basis of the calculation
      technique. With the use of the minimum detectable change calculation method with
      the Health Transition Index anchor, the minimum clinically important difference
      is 4.49 for VAS and 1.16 for BNI-PS after RFL for TN. ABBREVIATIONS: AUC, area
      under the receiver-operating characteristic curveBNI-PS, Barrow Neurological
      Institute Pain ScaleHTI, Health Transition IndexMCID, minimum clinically
      important differenceMDC, minimum detectable changePRO, patient-reported
      outcomeRFL, percutaneous stereotactic radiofrequency lesioningTN, trigeminal
      neuralgiaVAS, Visual Analog Scale.

PMID- 24335816
TI  - Long-term radiographic results of stent-assisted embolization of cerebral
      aneurysms.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage is a disabling disease.
      Endovascular coiling provides minimally invasive, effective, and safe treatment
      of both ruptured and unruptured intracranial aneurysms. Intracranial stents have
      improved the endovascular treatment of complex aneurysms, but the long-term
      durability of this treatment modality needs clarification. OBJECTIVE: To
      elucidate the long-term success of intracranial stent use in the treatment of
      aneurysms. METHODS: Four hundred ten patients were treated with stent-assisted
      endovascular management of 464 aneurysms. Treatment of 363 small aneurysms, 88
      large aneurysms, and 13 giant aneurysms was analyzed with respect to both long
      term anatomic results with digital subtraction angiography and magnetic resonance
      angiography over the follow-up period. RESULTS: The 6-month angiographic results
      of 387 aneurysm treatments revealed complete aneurysm occlusion in 282 (72.9%),
      residual aneurysm neck in 50 (12.9%), and residual aneurysm filling in 55
      (14.2%). Long-term radiographic follow-up, performed in 262 patients (mean, 3.63
      years), showed significant recurrence of only 3 aneurysms after 6-month follow-up
      imaging. Forty-eight aneurysms (11.9%) were considered radiographic failures
      during the follow-up period. CONCLUSION: The aneurysm recurrence rate after stent
      assisted embolization in this series was similar to published data using only
      coil embolization for the period between treatment and the initial follow-up
      imaging. For aneurysms that do not initially recur, the presented data suggest
      improved durability in the subsequent long-term follow-up period. ABBREVIATIONS:
      DSA, digital subtraction angiographyMRA, magnetic resonance angiography.

PMID- 24335817
TI  - Optic pathway gliomas in adults.
AB  - BACKGROUND: Optic pathway gliomas (OPGs) are considered relatively benign
      pediatric tumors. Adult patients with OPG can be divided into 2 groups: adult
      patients with tumors diagnosed in childhood and adult patients diagnosed during
      adulthood. OBJECTIVE: To characterize the clinical course of adult patients with
      OPG. METHODS: We retrospectively collected clinical and imaging data of all adult
      OPG patients monitored in our medical center between 1990 and 2012. RESULTS:
      Twenty-two adult patients were included. Age at diagnosis varied widely (6 months
      66 years), as did age at last follow-up (18-74 years). Ten patients were
      diagnosed at adulthood and 12 in childhood. Of the patients diagnosed at
      childhood, 6 had radiological progression during childhood, and 3 of those
      patients suffered visual impairment. From this group, 1 patient had further
      progression during adulthood accompanied by additional visual decline, and 2
      patients had additional visual decline during adulthood despite no signs of
      progression. Of the 6 patients whose tumors were stable during childhood, all 6
      remained stable during adulthood. Of 10 patients diagnosed at adulthood, 6
      patients suffered visual deterioration; in 5 of them, a concomitant progression
      was noted. Two patients were diagnosed with high-grade gliomas. CONCLUSION: OPGs
      may be active during childhood or adulthood. Those patients who experienced
      anatomic activity during childhood are prone to continue experiencing active
      disease during adulthood. A significant percentage of patients diagnosed with low
      grade OPG at adulthood may suffer progression, visual decline, or both.
      ABBREVIATIONS: NF1, neurofibromatosis 1OPG, optic pathway gliomas.

PMID- 24335818
TI  - Robotic autopositioning of the operating microscope.
AB  - BACKGROUND: Use of the operating microscope has become pervasive since its
      introduction to the neurosurgical world. Neuronavigation fused with the operating
      microscope has allowed accurate correlation of the focal point of the microscope
      and its location on the downloaded imaging study. However, the robotic ability of
      the Pentero microscope has not been utilized to orient the angle of the
      microscope or to change its focal length to hone in on a predefined target.
      OBJECTIVE: To report a novel technology that allows automatic positioning of the
      operating microscope onto a set target and utilization of a planned trajectory,
      either determined with the StealthStation S7 by using preoperative imaging or
      intraoperatively with the microscope. METHODS: By utilizing the current motorized
      capabilities of the Zeiss OPMI Pentero microscope, a robotic autopositioning
      feature was developed in collaboration with Surgical Technologies, Medtronic,
      Inc. (StealthStation S7). The system is currently being tested at the Barrow
      Neurological Institute. RESULTS: Three options were developed for automatically
      positioning the microscope: AutoLock Current Point, Align Parallel to Plan, and
      Point to Plan Target. These options allow the microscope to pivot around the
      lesion, hover in a set plane parallel to the determined trajectory, or rotate and
      point to a set target point, respectively. CONCLUSION: Integration of automatic
      microscope positioning into the operative workflow has potential to increase
      operative efficacy and safety. This technology is best suited for precise
      trajectories and entry points into deep-seated lesions.

PMID- 24335819
TI  - Stereotactic radiosurgery for neurofibromatosis 2-associated vestibular
      schwannomas: toward dose optimization for tumor control and functional outcomes.
AB  - BACKGROUND: Management of neurofibromatosis type 2 (NF2)-associated vestibular
      schwannomas (VSs) remains controversial. Stereotactic radiosurgery (SRS) with
      conventional dosing is less effective for NF2-related VS compared with sporadic
      lesions. OBJECTIVE: To evaluate optimal SRS dose parameters for NF2-related VS
      and to report long-term outcomes. METHODS: A prospective database was reviewed
      and outcome measures, including radiographic progression, American Academy of
      Otolaryngology-Head and Neck Surgery hearing class, and facial nerve function,
      were analyzed. Progression-free survival was estimated with Kaplan-Meier methods.
      Associations between tumor progression and radiosurgical treatment parameters,
      tumor volume, and patient age were explored with the use of Cox proportional
      hazards regression. RESULTS: Between 1990 and 2010, 26 patients with 32 NF2
      related VSs underwent SRS. Median marginal dose and tumor volume were 14 Gy and
      2.7 cm, respectively. Twenty-seven tumors (84%) showed no growth (median follow
      up, 7.6 years). Kaplan-Meier estimates for 5- and 10-year progression-free
      survival were 85% and 80%, respectively. Cox proportional hazards demonstrated a
      significant inverse association between higher marginal doses and tumor
      progression (hazard ratio, 0.49; 95% confidence interval, 0.17-0.92; P = .02).
      Audiometric data were available in 30 ears, with 12 having class A/B hearing
      before SRS. Only 3 maintained serviceable hearing at the last follow-up. Four
      underwent cochlear implantation. Initially, 3 achieved open-set speech
      recognition, although only 1 experienced long-term benefit. Facial nerve function
      remained stable in 50% of cases. CONCLUSION: Higher marginal doses than commonly
      prescribed for sporadic VS were associated with improved tumor control in
      patients with NF2. Hearing outcomes were poor even when contemporary reduced
      marginal doses were used. However, SRS allows an anatomically preserved cochlear
      nerve and may permit hearing rehabilitation with cochlear implantation. Further
      consideration should be given to optimum dosing to achieve long-term control
      while maximizing functional outcomes. ABBREVIATIONS: HB, House-BrackmannNF2,
      neurofibromatosis type 2SRS, stereotactic radiosurgeryVS, vestibular schwannoma.

PMID- 24335820
TI  - FLOW 800 allows visualization of hemodynamic changes after extracranial-to
      intracranial bypass surgery but not assessment of quantitative perfusion or flow.
AB  - BACKGROUND: FLOW 800 delivers a color-coded map for snapshot visualization of the
      temporal distribution dynamics after indocyanine green angiography with post hoc
      calculation of FLOW 800-specific hemodynamic parameters. However, the value of
      these parameters regarding quantitative flow assessment remains unclear.
      OBJECTIVE: To determine the value of FLOW 800-specific hemodynamic parameters in
      neurosurgical patients that permit assessment of hemodynamic changes within the
      microcirculation and macrocirculation. METHODS: FLOW 800 was performed in 25
      patients undergoing superficial temporal artery to middle cerebral artery bypass
      grafting and in 5 patients undergoing high- or intermediate-flow bypass grafting.
      The time to half-maximum fluorescence (t1/2max) and the cerebral blood flow index
      were calculated in the recipient vessel (macrocirculation) and the cortical
      territory (microcirculation) surrounding the anastomosis. For further evaluation,
      FLOW 800-specific hemodynamic parameters were compared with cortical laser
      speckle imaging and quantitative Doppler flow within the graft. RESULTS: FLOW 800
      provided color-coded information on the temporospatial distribution dynamics of
      the dye with excellent assessment of bypass patency. In the recipient vessel and
      in the cortical territory surrounding the anastomosis, FLOW 800 detected
      hemodynamic changes after superficial temporal artery to middle cerebral artery
      bypass grafting in terms of a significant decrease in t1/2max and increase in
      cerebral blood flow index. Interestingly, comparison of t1/2max with
      semiquantitative laser speckle imaging-specific cortical perfusion within the
      microcirculation demonstrated poor agreement, and neither t1/2max nor the
      cerebral blood flow index within the graft correlated with quantitative graft
      flow assessed by Doppler. CONCLUSION: FLOW 800 may detect procedure-related
      hemodynamic changes within the microcirculation and macrocirculation but should
      not be used as a stand-alone tool for quantitative flow assessment.

PMID- 24335821
TI  - 5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of
      visible fluorescence qualities as corroborated by spectrometry and histology and
      postoperative imaging.
AB  - BACKGROUND: 5-Aminolevulinic acid is used for fluorescence-guided resections.
      During resection, different macroscopic fluorescence qualities ("strong," "weak")
      can be distinguished that help guide resections. OBJECTIVE: This prospective
      study was designed to assess the reliability of visible fluorescence qualities by
      spectrometry, pathology, and imaging. METHODS: Thirty-three patients with
      malignant gliomas received 5-aminolevulinic acid (20 mg/kg). After debulking
      surgery, standardized biopsies were obtained from tissues with "weak" and
      "strong" fluorescence and from nonfluorescing near and distant brain for blinded
      assessment of cell density and tissue type (necrosis, solid or infiltrating
      tumor, normal tissue). The positive predictive value was calculated. Unresected
      fluorescing tissue was navigated for blinded correlation to postoperative
      magnetic resonance imaging (MRI). Receiver operating characteristic curves were
      generated for assessing the classification efficiency of spectrometry. RESULTS:
      "Strong" fluorescence corresponded to greater spectrometric fluorescence, solidly
      proliferating tumor, and high cell densities, whereas "weak" fluorescence
      corresponded to lower spectrometric fluorescence, infiltrating tumor, and medium
      cell densities. The positive predictive value was 100% in strongly fluorescing
      tissue and 95% in weakly fluorescing tissue. Spectrometric fluorescence was
      detected in marginal tissue without macroscopic fluorescence. Depending on the
      threshold, spectrometry displayed greater sensitivity but lower specificity
      (accuracy 88.4%). Residual MRI enhancement in the tumor bed was detected in 15 of
      23 (65%) patients with residual fluorescence, but in none of the patients without
      residual fluorescence. CONCLUSION: Macroscopic fluorescence qualities predict
      solid and infiltrating tumor, providing useful information during resection.
      Fluorescence appears superior to contrast enhancement on MRI for indicating
      residual tumor. Spectrometry, on the other hand, is more sensitive but less
      specific, depending on threshold definition. ABBREVIATIONS: 5-ALA, 5
      aminolevulinic acidCI, confidence intervalgamma-GT, gamma-glutamyl
      transpeptidaseGBM, glioblastoma multiformeNPV, negative predictive valuePPIX,
      protoporphyrin IXPPV, positive predictive valueSD, standard deviationWHO, World
      Health Organization.

PMID- 24335823
TI  - The era of flow diverters in aneurysm treatment.

PMID- 24335822
TI  - Arterial blood pressure management during carotid endarterectomy and early
      cognitive dysfunction.
AB  - BACKGROUND: A common practice during cross-clamp of carotid endarterectomy (CEA)
      is to manage mean arterial pressure (MAP) above baseline to optimize the
      collateral cerebral blood flow and reduce the risk of ischemic stroke. OBJECTIVE:
      To determine whether MAP management >=20% above baseline during cross-clamp is
      associated with lower risk of early cognitive dysfunction, a subtler form of
      neurological injury than stroke. METHODS: One hundred eighty-three patients
      undergoing CEA were enrolled in this ad hoc study. All patients had radial
      arterial catheters placed before the induction of general anesthesia. MAP was
      managed at the discretion of the anesthesiologist. All patients were evaluated
      with a battery of neuropsychometric tests preoperatively and 24 hours
      postoperatively. RESULTS: Overall, 28.4% of CEA patients exhibited early
      cognitive dysfunction (eCD). Significantly fewer patients with MAP >=20% above
      baseline during cross-clamp exhibited eCD than those managed <20% above (11.6% vs
      38.6%, P < .001). In a multivariate logistic regression model, MAP >=20% above
      baseline during the cross-clamp period was associated with significantly lower
      risk of eCD (odds ratio [OR], 0.18 [0.07-0.40], P < .001), whereas diabetes
      mellitus (OR, 2.73 [1.14-6.61], P = .03) and each additional year of education
      (OR, 1.19 [1.06-1.34], P = .003) were associated with significantly higher risk
      of eCD. CONCLUSION: The observations of this study suggest that MAP management
      >=20% above baseline during cross-clamp of the carotid artery may be associated
      with lower risk of eCD after CEA. More prospective work is necessary to determine
      whether MAP >=20% above baseline during cross-clamp can improve the safety of
      this commonly performed procedure.

PMID- 24335824
TI  - In reply: the era of flow diverters in aneurysm treatment.

PMID- 24335825
TI  - Microbial community dynamics and effect of environmental microbial reservoirs on
      red-backed salamanders (Plethodon cinereus).
AB  - Beneficial cutaneous bacteria on amphibians can protect against the lethal
      disease chytridiomycosis, which has devastated many amphibian species and is
      caused by the fungus Batrachochytrium dendrobatidis. We describe the diversity of
      bacteria on red-backed salamanders (Plethodon cinereus) in the wild and the
      stability of these communities through time in captivity using culture
      independent Illumina 16S rRNA gene sequencing. After field sampling, salamanders
      were housed with soil from the field or sterile media. The captive conditions led
      to different trajectories of bacterial communities. Eight OTUs present on >90% of
      salamanders in the field, through time, and in both treatments were defined as
      the core community, suggesting that some bacteria are closely associated with the
      host and are independent of an environmental reservoir. One of these taxa, a
      Pseudomonas sp., was previously cultured from amphibians and found to be
      antifungal. As all host-associated bacteria were found in the soil reservoir,
      environmental microbes strongly influence host-microbial diversity and likely
      regulate the core community. Using PICRUSt, an exploratory bioinformatics tool to
      predict gene functions, we found that core skin bacteria provided similar gene
      functions to the entire community. We suggest that future experiments focus on
      testing whether core bacteria on salamander skin contribute to the observed
      resistance to chytridiomycosis in this species even under hygenic captive
      conditions. For disease-susceptible hosts, providing an environmental reservoir
      with defensive bacteria in captive-rearing programs may improve outcomes by
      increasing bacterial diversity on threatened amphibians or increasing the
      likelihood that defensive bacteria are available for colonization.

PMID- 24335826
TI  - Intranuclear verrucomicrobial symbionts and evidence of lateral gene transfer to
      the host protist in the termite gut.
AB  - In 1944, Harold Kirby described microorganisms living within nuclei of the
      protists Trichonympha in guts of termites; however, their taxonomic assignment
      remains to be accomplished. Here, we identified intranuclear symbionts of
      Trichonympha agilis in the gut of the termite Reticulitermes speratus. We
      isolated single nuclei of T. agilis, performed whole-genome amplification, and
      obtained bacterial 16S rRNA genes by PCR. Unexpectedly, however, all of the
      analyzed clones were from pseudogenes of 16S rRNA with large deletions and
      numerous sequence variations even within a single-nucleus sample. Authentic 16S
      rRNA gene sequences were finally recovered by digesting the nuclear DNA; these
      pseudogenes were present on the host Trichonympha genome. The authentic sequences
      represented two distinct bacterial species belonging to the phylum
      Verrucomicrobia, and the pseudogenes have originated from each of the two
      species. Fluorescence in situ hybridization confirmed that both species are
      specifically localized, and occasionally co-localized, within nuclei of T.
      agilis. Transmission electron microscopy revealed that they are distorted cocci
      with characteristic electron-dense and lucent regions, which resemble the
      intranuclear symbionts illustrated by Kirby. For these symbionts, we propose a
      novel genus and species, 'Candidatus Nucleococcus trichonymphae' and 'Candidatus
      Nucleococcus kirbyi'. These formed a termite-specific cluster with database
      sequences, other members of which were also detected within nuclei of various gut
      protists, including both parabasalids and oxymonads. We suggest that this group
      is widely distributed as intranuclear symbionts of diverse protists in termite
      guts and that they might have affected the evolution of the host genome through
      lateral gene transfer. 

PMID- 24335827
TI  - Methanotrophic archaea possessing diverging methane-oxidizing and electron
      transporting pathways.
AB  - Anaerobic oxidation of methane (AOM) is a crucial process limiting the flux of
      methane from marine environments to the atmosphere. The process is thought to be
      mediated by three groups of uncultivated methane-oxidizing archaea (ANME-1, 2 and
      3). Although the responsible microbes have been intensively studied for more than
      a decade, central mechanistic details remain unresolved. On the basis of an
      integrated analysis of both environmental metatranscriptome and single-aggregate
      genome of a highly active AOM enrichment dominated by ANME-2a, we provide
      evidence for a complete and functioning AOM pathway in ANME-2a. All genes
      required for performing the seven steps of methanogenesis from CO2 were found
      present and actively expressed. Meanwhile, genes for energy conservation and
      electron transportation including those encoding F420H2 dehydrogenase (Fpo), the
      cytoplasmic and membrane-associated Coenzyme B-Coenzyme M heterodisulfide (CoB-S
      SCoM) reductase (HdrABC, HdrDE), cytochrome C and the Rhodobacter nitrogen
      fixation (Rnf) complex were identified and expressed, whereas genes encoding for
      hydrogenases were absent. Thus, ANME-2a is likely performing AOM through a
      complete reversal of methanogenesis from CO2 reduction without involvement of
      canonical hydrogenase. ANME-2a is demonstrated to possess versatile electron
      transfer pathways that would provide the organism with more flexibility in
      substrate utilization and capacity for rapid adjustment to fluctuating
      environments. This work lays the foundation for understanding the environmental
      niche differentiation, physiology and evolution of different ANME subgroups. 

PMID- 24335828
TI  - Distinct microbial communities associated with buried soils in the Siberian
      tundra.
AB  - Cryoturbation, the burial of topsoil material into deeper soil horizons by
      repeated freeze-thaw events, is an important storage mechanism for soil organic
      matter (SOM) in permafrost-affected soils. Besides abiotic conditions, microbial
      community structure and the accessibility of SOM to the decomposer community are
      hypothesized to control SOM decomposition and thus have a crucial role in SOM
      accumulation in buried soils. We surveyed the microbial community structure in
      cryoturbated soils from nine soil profiles in the northeastern Siberian tundra
      using high-throughput sequencing and quantification of bacterial, archaeal and
      fungal marker genes. We found that bacterial abundances in buried topsoils were
      as high as in unburied topsoils. In contrast, fungal abundances decreased with
      depth and were significantly lower in buried than in unburied topsoils resulting
      in remarkably low fungal to bacterial ratios in buried topsoils. Fungal community
      profiling revealed an associated decrease in presumably ectomycorrhizal (ECM)
      fungi. The abiotic conditions (low to subzero temperatures, anoxia) and the
      reduced abundance of fungi likely provide a niche for bacterial, facultative
      anaerobic decomposers of SOM such as members of the Actinobacteria, which were
      found in significantly higher relative abundances in buried than in unburied
      topsoils. Our study expands the knowledge on the microbial community structure in
      soils of Northern latitude permafrost regions, and attributes the delayed
      decomposition of SOM in buried soils to specific microbial taxa, and particularly
      to a decrease in abundance and activity of ECM fungi, and to the extent to which
      bacterial decomposers are able to act as their functional substitutes.

PMID- 24335831
TI  - Cervical cancer prevention: where are we?

PMID- 24335829
TI  - Seasonal fluctuations in ionic concentrations drive microbial succession in a
      hypersaline lake community.
AB  - Microbial community succession was examined over a two-year period using
      spatially and temporally coordinated water chemistry measurements, metagenomic
      sequencing, phylogenetic binning and de novo metagenomic assembly in the extreme
      hypersaline habitat of Lake Tyrrell, Victoria, Australia. Relative abundances of
      Haloquadratum-related sequences were positively correlated with co-varying
      concentrations of potassium, magnesium and sulfate, but not sodium, chloride or
      calcium ions, while relative abundances of Halorubrum, Haloarcula, Halonotius,
      Halobaculum and Salinibacter-related sequences correlated negatively with
      Haloquadratum and these same ionic factors. Nanohaloarchaea and Halorhabdus
      related sequence abundances were inversely correlated with each other, but not
      other taxonomic groups. These data, along with predicted gene functions from
      nearly-complete assembled population metagenomes, suggest different ecological
      phenotypes for Nanohaloarchaea and Halorhabdus-related strains versus other
      community members. Nucleotide percent G+C compositions were consistently lower in
      community metagenomic reads from summer versus winter samples. The same seasonal
      G+C trends were observed within taxonomically binned read subsets from each of
      seven different genus-level archaeal groups. Relative seasonal abundances were
      also linked to percent G+C for assembled population genomes. Together, these data
      suggest that extreme ionic conditions may exert selective pressure on archaeal
      populations at the level of genomic nucleotide composition, thus contributing to
      seasonal successional processes. Despite the unavailability of cultured
      representatives for most of the organisms identified in this study, effective
      coordination of physical and biological measurements has enabled discovery and
      quantification of unexpected taxon-specific, environmentally mediated factors
      influencing microbial community structure. 

PMID- 24335830
TI  - A bacterial pathogen uses dimethylsulfoniopropionate as a cue to target heat
      stressed corals.
AB  - Diseases are an emerging threat to ocean ecosystems. Coral reefs, in particular,
      are experiencing a worldwide decline because of disease and bleaching, which have
      been exacerbated by rising seawater temperatures. Yet, the ecological mechanisms
      behind most coral diseases remain unidentified. Here, we demonstrate that a coral
      pathogen, Vibrio coralliilyticus, uses chemotaxis and chemokinesis to target the
      mucus of its coral host, Pocillopora damicornis. A primary driver of this
      response is the host metabolite dimethylsulfoniopropionate (DMSP), a key element
      in the global sulfur cycle and a potent foraging cue throughout the marine food
      web. Coral mucus is rich in DMSP, and we found that DMSP alone elicits
      chemotactic responses of comparable intensity to whole mucus. Furthermore, in
      heat-stressed coral fragments, DMSP concentrations increased fivefold and the
      pathogen's chemotactic response was correspondingly enhanced. Intriguingly,
      despite being a rich source of carbon and sulfur, DMSP is not metabolized by the
      pathogen, suggesting that it is used purely as an infochemical for host location.
      These results reveal a new role for DMSP in coral disease, demonstrate the
      importance of chemical signaling and swimming behavior in the recruitment of
      pathogens to corals and highlight the impact of increased seawater temperatures
      on disease pathways. 

PMID- 24335832
TI  - Dual-channel spontaneous emission of quantum dots in magnetic metamaterials.
AB  - Metamaterials, artificial electromagnetic media realized by subwavelength nano
      structuring, have become a paradigm for engineering electromagnetic space,
      allowing for independent control of both electric and magnetic responses of the
      material. Whereas most metamaterials studied so far are limited to passive
      structures, the need for active metamaterials is rapidly growing. However, the
      fundamental question on how the energy of emitters is distributed between both
      (electric and magnetic) interaction channels of the metamaterial still remains
      open. Here we study simultaneous spontaneous emission of quantum dots into both
      of these channels and define the control parameters for tailoring the quantum-dot
      coupling to metamaterials. By superimposing two orthogonal modes of equal
      strength at the wavelength of quantum-dot photoluminescence, we demonstrate a
      sharp difference in their interaction with the magnetic and electric metamaterial
      modes. Our observations reveal the importance of mode engineering for spontaneous
      emission control in metamaterials, paving a way towards loss-compensated
      metamaterials and metamaterial nanolasers. 

PMID- 24335833
TI  - Plasmacytoid DCs, exposed to TSLP in synergy with TLR ligands, acquire
      significant potential towards Th2 polarization.
AB  - BACKGROUND: Thymic stromal lymphopoietin (TSLP) has been reported to activate
      myeloid dendritic cells (mDCs) to induce Th2 T lymphocyte responses. Its effect
      on plasmacytoid dendritic cells (pDCs) with TLR ligands has not yet been studied.
      We investigated the effects of TSLP and TLR ligands on mDCs and pDCs subsets.
      MATERIAL AND METHODS: Myeloid dendritic cells (mDC) and plasmacytoid dendritic
      cells (pDC) were stimulated by TLR ligands (mDC with TLR1/2 LTA, TLR2 PGN, TLR3
      poly I: C, TLR4 LPS, TLR5 Flagellin) (pDC with TLR9 CpG2006, CpG 2216, TLR7
      loxoribine) in the presence or absence of TSLP. Supernatants from mDCs and pDCs
      were analyzed for cytokine production. mDCs and pDCs were collected and cultured
      with allogeneic naive T cells and after 7 days of co-culture. DC-primed CD4+ T
      cells were washed and restimulated with PMA and ionomycin. Cytokine production in
      supernatants from restimulated cells - IL-4, IL-5, IL-10, IL-13, TNF-a was
      analyzed by Luminex. RESULTS: TSLP alone induced the expression of maturation
      markers on mDCs and increased their ability to polarize lymphocytes into the Th2
      phenotype. We demonstrated that pDCs also have the capacity to become even more
      potent inducers of Th2 immune responses, but only after combined treatment with
      TSLP and TLR ligands, particularly with TLR9 ligand CpG 2006. CONCLUSIONS: TSLP
      plays a major role in Th2 polarization of immune response mediated by myeloid
      DCs. Here, we demonstrate that plasmacytoid DCs, exposed to TSLP together with
      TLR ligands, acquire significant potential towards Th2 polarization.

PMID- 24335835
TI  - Annual Legislative Update marks the time to get informed, get involved.

PMID- 24335834
TI  - Symptom perceptions and self-care behaviors in patients who self-manage heart
      failure.
AB  - BACKGROUND: Patients with heart failure (HF) are at heightened risk for acute
      exacerbation requiring hospitalization. Although timely reporting of symptoms can
      expedite outpatient treatment and avoid the need for hospitalization, few
      patients recognize and respond to symptoms until acutely ill. OBJECTIVE: The
      purpose of this study was to explore patients' perceptions of symptoms and self
      care behaviors for symptom relief, leading up to a HF hospitalization. METHODS:
      To examine prehospitalization symptom scenarios, semistructured interviews were
      conducted with 60 patients hospitalized for acute decompensated HF. RESULTS:
      Thirty-seven patients (61.7%) said that they had a sense that "something just
      wasn't quite right" before their symptoms began but were unable to specify
      further. Signs and symptoms most often recognized by the patients were related to
      dyspnea (85%), fatigue (53.3%), and edema (41.7%). Few patients interpreted their
      symptoms as being related to worsening HF and most often attributed symptoms to
      changes in diet (18.3%) and medications (13.3%). Twenty-six patients (43.3%) used
      self-care strategies to relieve symptoms before hospital admission. More than 40%
      of the patients had symptoms at least 2 weeks before hospitalization.
      CONCLUSIONS: Despite the wide dissemination of HF evidence-based guidelines,
      important components of symptom self-management remain suboptimal. Because most
      of HF self-management occurs in the postdischarge environment, research is needed
      that identifies how patients interpret symptoms of HF in the specific contexts in
      which patients self-manage their HF. These findings suggest the need for
      interventions that will help patients expeditiously recognize, accurately
      interpret, and use appropriate and safe self-care strategies for symptoms.

PMID- 24335836
TI  - Bornyl caffeate induces apoptosis in human breast cancer MCF-7 cells via the ROS-
      and JNK-mediated pathways.
AB  - AIM: The purpose of the present study was to investigate the anticancer activity
      of bornyl caffeate in the human breast cancer cell line MCF-7. METHODS: The cell
      viability was determined using the MTT assay, and apoptosis was initially defined
      by monitoring the morphology of the cell nuclei and staining an early apoptotic
      biomarker with Annexin V-FITC. The mitochondrial membrane potential was
      visualized by JC-1 under fluorescence microscopy, whereas intracellular reactive
      oxygen species (ROS) were assessed by flow cytometry. The expression of apoptosis
      associated proteins was determined by Western blotting analysis. RESULTS: Bornyl
      caffeate induced apoptosis in MCF-7 cells in a dose- and time-dependent manner.
      Consistently, bornyl caffeate increased Bax and decreased Bcl-xl, resulting in
      the disruption of MMP and subsequent activation of caspase-3. Moreover, bornyl
      caffeate triggered the formation of ROS and the activation of the mitogen
      activated protein (MAP) kinases p38 and c-Jun N-terminal kinase (JNK).
      Antioxidants attenuated the activation of MAP kinase p38 but barely affected the
      activation of JNK. Importantly, the cytotoxicity of bornyl caffeate was partially
      attenuated by scavenging ROS and inhibited by MAP kinases and caspases.
      CONCLUSION: The present study demonstrated that bornyl caffeate induced apoptosis
      in the cancer cell line MCF-7 via activating the ROS- and JNK-mediated pathways.
      Thus, bornyl caffeate may be a potential anticancer lead compound.

PMID- 24335837
TI  - Protective effects of the novel adenosine derivative WS0701 in a mouse model of
      posttraumatic stress disorder.
AB  - AIM: To investigate the effects of the novel N6-substituted adenosine derivative
      {(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-[(4-hydroxy-3-methoxybenzyl)amino]-9H-purin-9
      yl]tetrahydrofuran-2-yl} methyl decanoate (WS0701) on stress-induced excessive
      fear, anxiety, and cognitive deficits in a mouse model of posttraumatic stress
      disorder (PTSD). METHODS: Male mice underwent a conditioned foot shock and single
      prolonged stress procedure to induce PTSD. Contextual/cued fear, elevated plus
      maze, open field and novel object recognition tests were conduced to assess PTSD
      like behaviors. From d 1, the mice were orally administered WS0701 (7.5, 15, or
      30 mg.kg(-1).d(-1)) or paroxetine (10 mg.kg(-1).d(-1)) for two weeks. Apoptosis
      of hippocampal neurons was detected using flow cytometry and TUNEL staining, and
      expression of Bcl-2 and Bax in the hippocampus was measured with Western boltting
      and qPCR assays. RESULTS: WS0701 administration significantly alleviated fear,
      anxious behaviors and memory deficits in the mouse model of PTSD. Furthermore,
      WS0701 administration significantly reduced the stress-induced apoptosis of
      hippocampal neurons, and increased the Bcl-2/Bax ratio in the hippocampus. The
      positive control drug paroxetine exerted similar effects on PTSD-like behaviors
      and hippocampal neuron apoptosis in the mouse model of PTSD, which were
      comparable to those caused by the high dose of WS0701. CONCLUSION: WS0701
      effectively mitigates stress-induced PTSD-like behaviors in mice, partly via
      inhibition of neuronal apoptosis in the hippocampus.

PMID- 24335838
TI  - Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in
      vitro via the NF-kappaB pathway.
AB  - AIM: To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor
      agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition
      of macrophage migration and the mechanisms underlying the effects of exendin-4.
      METHODS: Primary peritoneal macrophages were extracted from the peritoneal cavity
      of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages
      was examined using a cell migration assay. Macrophage migration-related factors
      including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor
      necrosis factor (TNF)-alpha, interleukin-1 (IL-1)beta, matrix metalloproteinase-2
      (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration
      inhibitory factor (MIF) were measured using semi-quantitative RT-PCR. Expression
      of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used
      to evaluate the activity of MMP-9. Activation of the NF-kappaB pathway was
      determined by confocal laser scanning microscopy. RESULTS: Treatment of the
      macrophages with ox-LDL (50 MUg/mL) markedly suppressed the macrophage migration.
      Furthermore, ox-LDL treatment substantially increased the expression of the
      macrophage migration-related factors, the activity of MMP-9 and the translocation
      of the NF-kappaB p65 subunit. These effects of ox-LDL were significantly
      ameliorated by pretreatment with the specific NF-kappaB inhibitor ammonium
      pyrrolidine dithiocarbamate (100 MUmol/L). These effects of ox-LDL were also
      significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L).
      CONCLUSION: Exendin-4 ameliorates the inhibition of ox-LDL on macrophage
      migration in vitro, via suppressing ox-LDL-induced expression of ICAM-1 and MIF,
      which is probably mediated by the NF-kappaB pathway.

PMID- 24335839
TI  - Ginsenoside Rg1 enhances the resistance of hematopoietic stem/progenitor cells to
      radiation-induced aging in mice.
AB  - AIM: To investigate the effects of ginsenoside Rg1 on the radiation-induced aging
      of hematopoietic stem/progenitor cells (HSC/HPCs) in mice and the underlying
      mechanisms. METHODS: Male C57BL/6 mice were treated with ginsenoside Rg1 (20
      mg.kg(-1).d(-1), ip) or normal saline (NS) for 7 d, followed by exposure to 6.5
      Gy X-ray total body irradiation. A sham-irradiated group was treated with NS but
      without irradiation. Sca-1(+) HSC/HPCs were isolated and purified from their bone
      marrow using MACS. DNA damage was detected on d 1. The changes of anti-oxidative
      activities, senescence-related markers senescence-associated beta-galactosidase
      (SA-beta-gal) and mixed colony-forming unit (CFU-mix), P16(INK4a) and
      P21(Cip1/Waf1) expression on d 7, and cell cycle were examined on d 1, d 3, and d
      7. RESULTS: The irradiation caused dramatic reduction in the number of Sca-1(+)
      HSC/HPCs on d 1 and the number barely recovered until d 7 compared to the sham
      irradiated group. The irradiation significantly decreased SOD activity, increased
      MDA contents and caused DNA damage in Sca-1(+) HSC/HPCs. Moreover, the
      irradiation significantly increased SA-beta-gal staining, reduced CFU-mix
      forming, increased the expression of P16(INK4a) and P21(Cip1/Waf1) in the core
      positions of the cellular senescence signaling pathways and caused G1 phase
      arrest of Sca-1(+) HSC/HPCs. Administration of ginsenoside Rg1 caused small, but
      significant recovery in the number of Sca-1(+) HSC/HPCs on d 3 and d 7.
      Furthermore, ginsenoside Rg1 significantly attenuated all the irradiation-induced
      changes in Sca-1(+) HSC/HPCs, including oxidative stress reaction, DNA damage,
      senescence-related markers and cellular senescence signaling pathways and cell
      cycle, etc. CONCLUSION: Administration of ginsenoside Rg1 enhances the resistance
      of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the
      oxidative stress reaction, reducing DNA damage, and regulating the cell cycle.

PMID- 24335840
TI  - Bioavailability, tissue distribution, and excretion characteristics of the novel
      carbonic anhydrase inhibitor tolsultazolamide in rats.
AB  - AIM: Tolsultazolamide, a novel carbonic anhydrase inhibitor, is designed for the
      prophylaxis and treatment of acute mountain sickness. The aim of this study was
      to investigate the pharmacokinetics, tissue distribution, and excretion
      characteristics of tolsultazolamide and the sex difference in pharmacokinetics in
      rats. METHODS: For pharmacokinetic study, rats were intravenously injected
      tolsultazolamide at 1 and 2 mg/kg or orally administered tolsultazolamide at 20,
      40, or 80 mg/kg) in a pharmacokinetic study. The concentrations of
      tolsultazolamide in plasma were determined with high-performance liquid
      chromatography, with a liquid-liquid extraction. For tissue distribution study,
      tolsultazolamide (80 mg/kg) was orally administered to overnight fasted rats (six
      per group and three per sex). Samples were collected from the brain, heart, lung,
      liver, spleen, muscle, kidney, stomach, fat, intestines, pancreas and sexual
      gland. For excretion study, tolsultazolamide (40 mg/kg) was orally administered
      to 6 rats (three per sex). The urine, feces, and bile samples were collected at
      24, 48, and 72 h. RESULTS: After its intravenous administration, tolsultazolamide
      was rapidly eliminated from the plasma, with T1/2 of about 60-90 min. The AUC0-t
      and the initial concentration (C0) values were proportional to the intravenous
      doses. After its oral administration, tolsultazolamide showed dose-independent
      pharmacokinetic characteristics, with Tmax and T1/2 of approximately 2 h and 5-7
      h, respectively, and good oral absolute bioavailability of about 60%.
      Tolsultazolamide was distributed widely in various tissues. The highest
      tolsultazolamide levels were detected in the stomach, intestine, spleen, lung,
      and kidney. Total excretion of unchanged tolsultazolamide in the urine, feces,
      and bile was less than 2%. The Cmax and AUC of tolsultazolamide were
      significantly higher in female rats than those in male rats. Clearance and volume
      of distribution were greater in male rats than those in female rats. The oral
      absolute bioavailability was also significantly different between female rats
      (about 83%) and male rats (about 37%). CONCLUSION: Tolsultazolamide was well
      absorbed and widely distributed in the rat, and very little of the unchanged form
      was excreted. Sex had a significant effect on the pharmacokinetics of
      tolsultazolamide.

PMID- 24335841
TI  - Exercise ameliorates the detrimental effect of chloroquine on skeletal muscles in
      mice via restoring autophagy flux.
AB  - AIM: To study the roles of autophagy in muscle establishment during long-term
      exercise in mice. METHODS: Female ICR mice were submitted to exercise training
      with a wheel running regimen: 6 m/min, 15 min/time, 3 times/d (on 8:00, 14:00,
      and 20:00), 5 d/week for 2 months. The mice were treated with the autophagy
      activator trehalose (1% aqueous solution as a daily drinking water) or the
      autophagy inhibitor chloroquine (10 mg/kg, ip, 5 times a week) before the
      training. Western blotting analysis, TUNEL staining, H&E staining and
      transmission electron microscope were used to evaluate the activity of autophagy
      and the structure of the muscle fibers. RESULTS: The exercise training
      significantly stimulated the formation of autophagosomes, increased the LC3-II,
      cathepsin L and Bcl-2 levels, lowered the P62 level and increased the antioxidant
      capacity in the muscles. Meanwhile, the exercise training significantly improved
      the morphology of mitochondria, reduced the release of cytochrome c from
      mitochondria to cytoplasm, and slightly decreased the apoptosis rate in the
      muscles. Administration of trehalose increased the level of autophagy and
      protected the muscle fibers from apoptosis. Administration of chloroquine blocked
      autophagy flux and exerted detrimental effects on the muscles, which were
      ameliorated by the exercise training. CONCLUSION: Long-term regular exercise
      activates autophagy process associated with muscle establishment, and ameliorates
      the detrimental effects of chloroquine on skeletal muscles via restoring
      autophagy flux.

PMID- 24335842
TI  - Structure-based ensemble-QSAR model: a novel approach to the study of the EGFR
      tyrosine kinase and its inhibitors.
AB  - AIM: To develop a novel 3D-QSAR approach for study of the epidermal growth factor
      receptor tyrosine kinase (EGFR TK) and its inhibitors. METHODS: One hundred
      thirty nine EGFR TK inhibitors were classified into 3 clusters. Ensemble docking
      of these inhibitors with 19 EGFR TK crystal structures was performed. Three
      protein structures that showed the best recognition of each cluster were selected
      based on the docking results. Then, a novel QSAR (ensemble-QSAR) building method
      was developed based on the ligand conformations determined by the corresponding
      protein structures. RESULTS: Compared with the 3D-QSAR model, in which the ligand
      conformations were determined by a single protein structure, ensemble-QSAR
      exhibited higher R2 (0.87) and Q2 (0.78) values and thus appeared to be a more
      reliable and better predictive model. Ensemble-QSAR was also able to more
      accurately describe the interactions between the target and the ligands.
      CONCLUSION: The novel ensemble-QSAR model built in this study outperforms the
      traditional 3D-QSAR model in rationality, and provides a good example of
      selecting suitable protein structures for docking prediction and for building
      structure-based QSAR using available protein structures.

PMID- 24335843
TI  - (-)Doxazosin is a necessary component for the hypotensive effect of (+/
      )doxazosin during long-term administration in conscious rats.
AB  - AIM: Doxazosin is a racemic mixture of (-)doxazosin and (+)doxazosin that is
      currently used as an add-on therapy for hypertension. In this study we
      investigated the contribution of each enantiomer to the hypotensive action of
      long-term administration of (+/-)doxazosin in conscious rats. METHODS: Blood
      pressure of conscious SD rats was measured using a volume pressure recording
      system. The rats were orally administered (-)doxazosin, (+)doxazosin, or (+/
      )doxazosin (8 mg.kg(-1).d(-1)) for 12 weeks. Plasma concentrations of the agents
      were analyzed with HPLC. The effect of the agents on alpha1-adrenoceptor was
      examined in isolated rat caudal artery preparations. RESULTS: Treatment of
      conscious rats with a single dose of (+/-)doxazosin (8 mg/kg) did not affected
      DBP and MBP, but significantly decreased SBP by 11.9% 4 h after the
      administration. Long-term treatment of conscious rats with (+/-)doxazosin
      significantly decreased SBP, DBP and MBP with a maximal decrease of SBP by 29.3%
      8 h after the last administration. The rank order of the hypotensive actions
      caused by long-term treatment in conscious rats was (+/
      )doxazosin>(+)doxazosin>>(-)doxazosin. However, the pKB values for inhibiting NA
      induced contraction of isolated rat caudal artery were (+)doxazosin (8.995)>(+/
      )doxazosin (8.694)>(-)doxazosin (8.032). The plasma concentrations of (
      )doxazosin, (+)doxazosin, and (+/-)doxazosin were 18.26+/-3.55, 177.11+/-20.66,
      and 113.18+/-13.21 ng/mL, respectively, 8 h after the last administration of
      these agents. CONCLUSION: Long-term treatment with (+/-)doxazosin produces potent
      hypotensive action in conscious rats that seems to result from synergic
      interaction of the two enantiomers.

PMID- 24335845
TI  - All-back-contact ultra-thin silicon nanocone solar cells with 13.7% power
      conversion efficiency.
AB  - Thinner Si solar cells with higher efficiency can make a Si photovoltaic system a
      cost-effective energy solution, and nanostructuring has been suggested as a
      promising method to make thin Si an effective absorber. However, thin Si solar
      cells with nanostructures are not efficient because of severe Auger recombination
      and increased surface area, normally yielding <50% EQE with short-wavelength
      light. Here we demonstrate >80% EQEs at wavelengths from 400 to 800 nm in a sub
      10-MUm-thick Si solar cell, resulting in 13.7% power conversion efficiency. This
      significant improvement was achieved with an all-back-contact design preventing
      Auger recombination and with a nanocone structure having less surface area than
      any other nanostructures for solar cells. The device design principles presented
      here balance the photonic and electronic effects together and are an important
      step to realizing highly efficient, thin Si and other types of thin solar cells. 

PMID- 24335844
TI  - Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute
      pain in mice.
AB  - AIM: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to
      alleviate inflammatory and neuropathic pain in rats. In the present study, we
      investigated the effects of AZA on thermal- and chemical-stimulated acute pain in
      mice and the possible mechanisms underlying the effects. METHODS: Five acute pain
      models based on thermal and chemical stimuli were established to investigate the
      effects of AZA on different types of nociception in mice. The antinociceptive
      effects of methazolamide (another CA inhibitor) and diazepam (a positive
      allosteric modulator of GABAA receptor) were also examined. The drugs were
      administered either intraperitoneally (ip) or intrathecally. RESULTS: AZA (50-200
      mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models,
      ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50-200 mg/kg, ip)
      dose-dependently reduced paw licking time in both capsaicin and formalin tests in
      mice. A similar result was observed in a mouse acetic acid-induced writhing test.
      However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia
      in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50
      200 mg/kg, ip) and diazepam (0.25-1.0 mg/kg, ip) did not produce significant
      analgesia in either thermal- or chemical-stimulated acute pain. CONCLUSION: AZA
      produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain
      in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due
      to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity
      but rather a peripheral ion channel-related mechanism.

PMID- 24335846
TI  - Procedural justice in prison: the importance of staff characteristics.
AB  - A humane and fair treatment of prisoners is of intrinsic value in itself, and is
      generally acclaimed to reduce prisoners' psychological distress and misconduct in
      prison, and their criminal behavior after release from prison. To create a more
      just prison climate, scholars have emphasized the importance of correctional
      staff. However, there is a lack of empirical research on the relationship between
      correctional officers' characteristics and prisoners' perceptions of a just
      treatment in prison. Our study fills this gap in knowledge. Data were used from
      (a) the Prison Project, a large-scale study in which prisoners held in all Dutch
      remand centers were surveyed (n = 1,610) and (b) the Dutch Correctional Staff
      Survey 2011 (n = 690). Multilevel analyses showed that prisoners perceived their
      treatment in prison as more procedurally just in units where there are more
      female officers, where officers held more positive attitudes toward
      rehabilitation, and where there is a higher officer-to-inmate ratio. 

PMID- 24335847
TI  - Disentangling criminal profiling: accuracy, homology, and the myth of trait-based
      profiling.
AB  - The scholarly literature over the past decade has chronicled a growing problem in
      the forensic technique colloquially called criminal profiling. The basis of this
      conundrum appears to originate from a concept referred to as "offender homology,"
      which presumes an inherent uniformity among offenders that is believed to
      underpin the analytic process incumbent to criminal profiling. Studies thus far
      conducted have apparently struggled to find evidence of offender homology, and
      based upon these findings arguments have been promulgated that various approaches
      to criminal profiling imputably labeled as "trait-based" are therefore not
      viable. Indirectly contradicting these arguments, however, have been studies
      testing profiler accuracy that have found evidence of individuals who appear to
      use trait-based methods but can nonetheless proficiently predict the
      characteristics of unknown offenders. Against this backdrop, the present article
      examines a number of tenets and disjunctions that appear to have arisen from
      research into offender homology and imputed to the practices of so-called trait
      based profiling. The notion of whether trait-based profiling is, in fact,
      representative of profiling methods is examined and an integrative hypothesis
      proposed that attempts to resolve the quandary between offender homology and
      profiler accuracy. 

PMID- 24335848
TI  - A comparative study of candesartan versus propranolol for migraine prophylaxis: A
      randomised, triple-blind, placebo-controlled, double cross-over study.
AB  - OBJECTIVE: The objective of this article is to see whether the effect of
      candesartan for migraine prevention, shown in one previous study, could be
      confirmed in a new study, and if so, whether the effect was comparable to that of
      propranolol (non-inferiority analysis), and whether adverse events were
      different. METHODS: In a randomised, triple-blind, double cross-over study, 72
      adult patients with episodic or chronic migraine went through three 12-week
      treatment periods on either candesartan 16 mg, propranolol slow-release 160 mg,
      or placebo. The main outcome measures were days with migraine headache per four
      weeks (primary outcome), days with headache, hours with headache, proportion of
      responders (>50% reduction of migraine days from baseline), and adverse events.
      RESULTS: In the modified intention-to treat-analysis, candesartan and propranolol
      were both superior to placebo: 2.95 (95% confidence interval: 2.35-3.55%) and
      2.91 (2.36-3.45%), versus 3.53 (2.98-4.08%) for migraine days per month (p = 0.02
      for both comparisons, Wilcoxon's paired signed rank test, blinded statistical
      analysis). Candesartan was non-inferior to propranolol (and vice versa). The
      proportion of responders was significantly higher on candesartan (43%) and
      propranolol (40%) than on placebo (23%) (p = 0.025 and <0.050, respectively).
      There were more adverse events on candesartan (n = 133%) and propranolol (n =
      143%) than on placebo (n = 90%), and the adverse event profiles of the active
      substances differed somewhat. CONCLUSION: It is confirmed that candesartan 16 mg
      is effective for migraine prevention, with an effect size similar to propranolol
      160 mg, and with somewhat different adverse events. TRIAL REGISTRATION: EUDRACT
      (2008-002312-7), ClinicalTrials.gov (NCT00884663).

PMID- 24335849
TI  - Adding NSAIDs to triptans: could less be more?

PMID- 24335850
TI  - Monthly variation of United States pediatric headache emergency department
      visits.
AB  - OBJECTIVE: The objective of this article is to determine the monthly variation of
      emergency department (ED) visits for pediatric headache. We hypothesized youth
      have increased headache-related ED visits in the months associated with school
      attendance. METHODS: Using a United States representative sample of ED visits in
      the National Hospital Ambulatory Medical Care Survey from 1997 to 2009, we
      estimated number of visits associated with ICD-9 codes related to headache,
      migraine, status migrainosus, or tension-type headache in 5- to 18-year-olds. Age
      stratified multivariate models are presented for month of visit (July as
      reference). RESULTS: There was a national estimate of 250,000 ED visits annually
      related to headache (2.1% of total visits) in 5- to 18-year-olds. In 5- to 11
      year-olds, the adjusted rate of headache-related visits was lower in April (OR
      0.42, 95% CI 0.20, 0.88). In 12- to 18-year-olds, there were higher rates in
      January (OR 1.92, 95% CI 1.16, 3.14) and September (OR 1.64, 95% CI 1.06, 2.55).
      CONCLUSIONS: In adolescents we found higher ED utilization in January and
      September, the same months associated with school return from vacation for a
      majority of children nationally. No significant reduction in the summer suggests
      that school itself is not the issue, but rather changes in daily lifestyle and
      transitions.

PMID- 24335851
TI  - Imprecise diagnosis of migraine with aura in the Women's Health Study. Does it
      matter?

PMID- 24335853
TI  - Acute stroke, Bayes' theorem and the art and science of emergency decision
      making.

PMID- 24335852
TI  - Increased susceptibility to cortical spreading depression in an animal model of
      medication-overuse headache.
AB  - OBJECTIVE: The objective of this article is to evaluate electrically evoked
      thresholds for cortical spreading depression (CSD) and stress-induced activation
      of trigeminal afferents in a rat model of medication-overuse headache (MOH).
      METHODS: Sumatriptan or saline was delivered subcutaneously by osmotic minipump
      for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were
      anesthetized and recording/stimulating electrodes implanted. The animals were
      pretreated with vehicle or topiramate followed by graded electrical stimulation
      within the visual cortex. CSD events were identified by decreased EEG amplitude
      and DC potential shift. Additional unanesthetized sumatriptan or saline
      pretreated rats were exposed to bright light environmental stress and periorbital
      and hindpaw withdrawal thresholds were measured. Following CSD stimulation or
      environmental stress, immunohistochemical staining for Fos in the trigeminal
      nucleus caudalis (TNC) was performed. RESULTS: Sumatriptan pre-exposure
      significantly decreased electrical stimulation threshold to generate a CSD event.
      Topiramate normalized the decreased CSD threshold as well as stress-induced
      behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline
      treated animals. Moreover, CSD and environmental stress increased Fos expression
      in the TNC of sumatriptan-treated rats, and these effects were blocked by
      topiramate. Environmental stress did not elicit cutaneous allodynia or elevate
      TNC Fos expression in saline-treated rats. CONCLUSIONS: A previous period of
      sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD
      and environmental stress-induced activation of the TNC that was prevented by
      topiramate. Lowered CSD threshold, and enhanced consequences of CSD events
      (increased activation of TNC), may represent an underlying biological mechanism
      of MOH related to triptans.

PMID- 24335854
TI  - The current and future role of the medical oncologist in the professional care
      for cancer patients: a position paper by the European Society for Medical
      Oncology (ESMO).
AB  - The number of cancer patients in Europe is rising and significant advances in
      basic and applied cancer research are making the provision of optimal care more
      challenging. The concept of cancer as a systemic, highly heterogeneous and
      complex disease has increased the awareness that quality cancer care should be
      provided by a multidisciplinary team (MDT) of highly qualified healthcare
      professionals. Cancer patients also have the right to benefit from medical
      progress by receiving optimal treatment from adequately trained and highly
      skilled medical professionals. Built on the highest standards of professional
      training and continuing medical education, medical oncology is recognised as an
      independent medical specialty in many European countries. Medical oncology is a
      core member of the MDT and offers cancer patients a comprehensive and systemic
      approach to treatment and care, while ensuring evidence-based, safe and cost
      effective use of cancer drugs and preserving the quality of life of cancer
      patients through the entire 'cancer journey'. Medical oncologists are also
      engaged in clinical and translational research to promote innovation and new
      therapies and they contribute to cancer diagnosis, prevention and research,
      making a difference for patients in a dynamic, stimulating professional
      environment. Medical oncologists play an important role in shaping the future of
      healthcare through innovation and are also actively involved at the political
      level to ensure a maximum contribution of the profession to Society and to tackle
      future challenges. This position paper summarises the multifarious and vital
      contributions of medical oncology and medical oncologists to today's and
      tomorrow's professional cancer care. 

PMID- 24335856
TI  - Coercive paternalism and back-door perfectionism.
AB  - In this response piece, I argue that the 'coercive paternalism' that Sarah Conly
      endorses in her book Against Autonomy veers towards a back-door perfectionism.
      Although Conly points out that coercive paternalism does not mandate the
      imposition of alien values upon us in the same way that perfectionism does, I
      argue that coercive paternalism might yet impose an alien weighting of our own
      values; this, I suggest, means that coercive paternalism remains perfectionist in
      spirit, if not in letter. I go on to concede to Conly that coercive paternalism
      might be warranted in preventing actions that threaten health and that are only
      carried out on the basis of cognitive error. However, I conclude by claiming that
      we must take great care about what we presume that people are consuming only on
      the basis of cognitive error. More specifically, I suggest that it is crucial
      that we avoid defining our terms in such a manner that it becomes impossible for
      agents to choose some action that poses a risk to their health without them being
      accused of making a cognitive error in weighing their values in that way. 

PMID- 24335855
TI  - Impact of psychological distress on cardiovagal reactivation after a speech task.
AB  - Cardiovascular disease (CVD) is more prevalent in individuals with Type-D
      personality(distressed) who tend to avoid confrontation in social situations
      (social inhibition) and have a greater tendency to experience negative emotions
      (negative affectivity). Although psychological distress is associated with
      increased risk of adverse cardiovascular outcomes and impaired heart rate (HR)
      modulation, studies examining cardiac autonomic modulation in distressed
      individuals through heart rate variability (HRV) and baroreflex functioning
      during, and more importantly, after stress are scarce. Accordingly, we
      investigated blood pressure (BP), baroreflex sensitivity (BRS) and HRV responses
      before, during and after an interpersonal speech task (ST) in individuals with
      high distress scores (HD) and low distress scores (LD).

PMID- 24335857
TI  - Paternalism, French fries and the weak-willed Witness.

PMID- 24335858
TI  - Human dignity in bioethics and law.

PMID- 24335859
TI  - Summary of unfit for the future.

PMID- 24335860
TI  - Death, posthumous harm, and bioethics.

PMID- 24335861
TI  - Something to celebrate: living with HIV in later life.

PMID- 24335862
TI  - The continuity of care: should the six Cs be seven?

PMID- 24335863
TI  - Optimising wound care in a child with an infected gastrostomy exit site.
AB  - The percutaneous endoscopic gastrostomy (PEG) tube has become a widely used
      feeding tube for long-term delivery of fluids, liquid feed and medicines. PEG
      tube insertion can be considered a minimally invasive technique, associated with
      rapid recovery and early discharge from hospital but is not without risk
      (Vervloessem et al 2009; Naiditch et al 2010). A lack of nationally agreed,
      evidence-based clinical practice guidelines makes PEG exit site care a matter of
      local clinical practice and clinical judgement. In paediatric practice, children
      experience care shared across several healthcare settings, meeting clinical teams
      with varying levels of knowledge and experience of PEG care. This can lead to
      conflicting advice, which can have a negative effect on patient safety and
      experience. The case history in this article demonstrates how PEG tube insertion
      is never a minor procedure for a child and family (Vervloessem et al 2009;
      Khattak et al 1998). It highlights areas of potential conflict in clinical
      management of PEG exit sites, and it shows how application of wound care
      principles, along with a range of modern products can have a positive outcome. 

PMID- 24335864
TI  - Managing high-output stomas: module 3 of 3.
AB  - Enterocutaneous fistulae (ECF) and high-output stomas are challenging to manage,
      owing to the large volume of loss that may result in severe dehydration,
      electrolyte imbalances, malnutrition and sepsis. It is imperative that this group
      of patients receive adequate nutrition, as malnutrition and sepsis are the
      leading cause of death. Treatment is complex and based on various situations,
      treatment can be medical/conservative management or surgical. Depending on the
      site of the fistula and the length of residual intestine contributing as the
      cause of a high output stoma with the nutritional status of the patient,
      clinicians have to decide whether parenteral nutrition (PN) or enteral nutrition
      (EN) should be established. As previously discussed in module 1 and 2 (Gabe,
      2013; Gabe and Slater, 2013) the theme of nutritional management and
      appliance/accessory selection to manage patients with ECF and high output stomas
      was outlined. The aim of providing an understanding of the nutritional needs and
      the practicalities of maintaining appliance adherence, and in turn, a reduction
      in the breakdown of the peri-stomal skin was described. Module 3 aims to provide
      understanding for the reader that may encounter patients undergoing surgery for
      the management of their ECF or high-output stoma. Lastly it was felt necessary to
      discuss the subject of intestinal transplantation. This complex surgical option
      is not available to all patients with intestinal failure and only undertaken at a
      couple of recognised centres. The process of referring patients that are deemed
      suitable for intestinal transplantation will be addressed and what the surgery
      entails with long-term outcomes and the quality of life for the patient. 

PMID- 24335865
TI  - Parental management of eczema.

PMID- 24335866
TI  - Acute decompensated heart failure: diagnosis and management.
AB  - Chronic heart failure is common in the UK, with a prevalence estimated at 3% of
      people aged between 65 and 74 years. This prevalence increases with age and
      affects approximately 15% of the older population (British Heart Foundation,
      2011). A significant number of such people are diagnosed after presenting to
      their local emergency department with severe breathlessness. Advances in patient
      management have improved outcomes, but the prognosis remains poor. A recent
      epidemiological study of patients with heart failure in north west London
      reported that around 14% of patients die within 6 months of diagnosis (Mehta et
      al, 2009). The UK national audit data of 2011-2012 reported that approximately
      11% of patients admitted to hospital with acute heart failure die during their in
      hospital stay. For those discharged, there is a greater-than-25% risk of death
      within 12 months. This risk of in-hospital and 12-month mortality varies widely,
      but appears to largely relate to the inpatient management and organisation of
      follow-up (National Institute for Cardiovascular Outcomes Research, 2012).

PMID- 24335867
TI  - African and Afro-Caribbean men's experiences of prostate cancer.
AB  - It is well documented that prostate cancer presents a significant health problem
      for middle-aged and elderly men in the UK, with further evidence suggesting that
      the disease is more prevalent in men of African and Afro-Caribbean (AAC)
      ethnicity. There is also evidence that these men are diagnosed much later and
      that the disease is more aggressive than in Caucasian men. AIM: To explore AAC
      men's experiences of prostate cancer and their understanding of its associated
      risks. The purpose was to gain an insight from these men's perspectives and
      ascertain whether a more focused health promotion strategy, and specific UK-based
      research, was needed in this area. METHOD: A purposive sample of seven AAC men
      was recruited from a hospital trust's patient list after gaining approval from a
      research ethics committee. In-depth face-to-face interviews were carried out and
      the transcripts analysed thematically. FINDINGS: The four main themes that
      emerged were: disease-prompted awareness, checking up as a necessary evil,
      defining and constructing factors influencing prostate cancer screening uptake,
      and appraising perceived myths about prostate cancer through personal beliefs.
      CONCLUSIONS: Among this group of AAC men, socioeconomic status, such as education
      and professional background, were factors that influenced their level of
      awareness of prostate cancer and prompted their decisions to seek help. However,
      it is evident from these men's perspectives that a more specific health education
      strategy that promotes early detection and management, targeting AAC men, would
      help in demystifying prostate cancer and encourage them to seek help earlier.
      Further research studies and health education in prominent social outlets are
      recommended in increasing AAC men's awareness of prostate cancer and its
      associated risks.

PMID- 24335868
TI  - Raising public awareness of hepatitis B and C through a testing road show.
AB  - Over the past decade, as the profile of hepatitis B and C has been raised, a
      range of nurse-led services has been developed among substance misuse services,
      prisons and homeless services to reach those at the highest risk of infection. In
      the UK, it is estimated that up to two-thirds of people with hepatitis C are
      unaware of their infection (Cornberg et al, 2011). These patients represent those
      at the highest risk of developing cirrhosis and liver cancer, and many are
      unlikely to be in contact with services that offer routine testing. To help
      address this, the Welsh Hepatitis Nurse Forum (WHNF) carried out two road shows
      aimed at raising awareness of hepatitis B and C among the general public and
      offering testing. This paper describes the process, results and evaluation of the
      road shows that took place in 2011 and 2012. The road show is a unique way in
      which nurses can reach those who may not have regular contact with health
      services, and has proved useful for generally raising awareness. Further work is
      needed to evaluate the cost-effectiveness of the road shows. 

PMID- 24335869
TI  - Lost in transition: child to adult cancer services for young people.
AB  - Cancer nursing care across the UK has dramatically improved for children and
      young people with cancer over the past 20 years (Department of Health, 2007).
      Around 70% of young people diagnosed with cancer survive into adulthood, albeit
      with long-term health complications (Scottish Government, 2012). This raises the
      contemporary concern of how best to transition these patients to an adult-focused
      care regime (National Cancer Survivorship Initiative, 2012). With support from a
      Florence Nightingale Foundation Travel Scholarship in 2012, this study compared
      the various transition models currently in use across the UK, Finland and the USA
      with a clear focus on individual patient choice, staff education and preparation
      to care for this group of patients and their families. The findings revealed wide
      discrepancy in current nursing practices across the globe. This article presents
      a series of findings and recommendations to improve further the overall cancer
      experience for young people living with and beyond a cancer diagnosis.

PMID- 24335870
TI  - Family-centred care: theory to practice.

PMID- 24335871
TI  - Clinical supervision: from staff nurse to nurse consultant. Part a: prioritising
      and making time.

PMID- 24335872
TI  - Courage and medical innovation: the nurses of World War One.

PMID- 24335873
TI  - Protecting health through public health law.
AB  - The report into the outbreak of measles in the Swansea area in 2013 has
      recommended that public health law be used as a routine response to minimising
      the spread of infectious diseases. In this article, the author considers what
      powers are available to health and local authorities to minimise the spread of an
      infectious disease outbreak. 

PMID- 24335874
TI  - Preventing ill health in childhood.

PMID- 24335875
TI  - Trends in emergency admission for fractured neck of femur.

PMID- 24335876
TI  - Using patient stories in the NHS.

PMID- 24335877
TI  - Kit preparation and biokinetics in women of 99mTc-EDDA/HYNIC-E-[c(RGDfK)]2 for
      breast cancer imaging.
AB  - BACKGROUND: In breast cancer, alpha(nu)beta(3) and/or alpha(nu)beta(5) integrins
      are overexpressed in both endothelial and tumour cells. Radiolabelled peptides
      based on the Arg-Gly-Asp (RGD) sequence are radiopharmaceuticals with high
      affinity and selectivity for these integrins. The RGD-dimer peptide (E
      [c(RGDfK)]2) radiolabelled with (99m)Tc has been reported as a
      radiopharmaceutical with a 10-fold higher affinity for the alpha(nu)beta(3)
      integrin compared with the RGD-monomer. Ethylenediamine-N,N'-diacetic acid (EDDA)
      is a hydrophilic molecule that may favour renal excretion when used as coligand
      in the (99m)Tc labelling of hydrazinonicotinamide (HYNIC) peptides and can easily
      be formulated in a lyophilized kit. AIM: The aim of this study was to establish a
      biokinetic model for (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 prepared from lyophilized
      kits and evaluate its dosimetry as a tumour-imaging agent in seven healthy women
      and three breast cancer patients. MATERIALS AND METHODS: (99m)Tc labelling was
      performed by adding sodium pertechnetate solution and 0.2 mol/l phosphate buffer
      (pH 7.0) to a lyophilized formulation containing E-[c(RGDfK)]2, EDDA, tricine,
      mannitol and stannous chloride. The radiochemical purity was evaluated using
      reverse-phase high-performance liquid chromatography and instant thin-layer
      chromatography on silica gel analyses. Stability studies in human serum were
      carried out using size-exclusion high-performance liquid chromatography. In-vitro
      cell uptake was tested using breast cancer cells (MCF7, T47D and MDA-MB-231) with
      blocked and nonblocked receptors. Biodistribution and tumour uptake were
      determined in MCF7 tumour-bearing nude mice with blocked and nonblocked
      receptors, and images were obtained using a micro-SPECT/PET/CT. Whole-body images
      from seven healthy women were acquired at 0.5, 1, 3, 6 and 24 h after (99m)Tc
      EDDA/HYNIC-E-[c(RGDfK)]2 administration with radiochemical purities greater than
      94%. Regions of interest were drawn around the source organs at each time frame.
      Each region of interest was converted to activity using the conjugate view
      counting method. The image sequence was used to extrapolate the (99m)Tc
      EDDA/HYNIC-E-[c(RGDfK)]2 time-activity curves of each organ to adjust the
      biokinetic model and calculate the total number of disintegrations (N) that
      occurred in the source regions. N data were the input for the OLINDA/EXM code to
      calculate internal radiation dose estimates. In three breast cancer patients with
      histologically confirmed cancer, static images were obtained at 1 h in the supine
      position with hands placed behind the head. RESULTS: (99m)Tc-EDDA/HYNIC-E
      [c(RGDfK)]2 obtained from lyophilized kits demonstrated high stability in human
      serum and specific cell receptor binding. The biodistribution data from mice
      showed rapid blood clearance, with both renal and hepatobiliary excretion, and
      specific binding towards alpha(nu)beta(3) integrins in the MCF7 tumours. In
      women, the blood activity showed a half-life value of 1.60 min for the fast
      component (T1/2alpha = ln2/26.01) and half-life values of 1.0 h for the first
      slow component (T1/2beta = ln2/0.69) and 4.03 h for the second slow component
      (T1/2gamma = ln2/0.16). Images from patients showed an average tumour/heart
      (blood) ratio of 3.61 +/- 0.62 at 1 h. The average equivalent doses calculated
      for a study using 740 MBq were 4.9, 6.2, 20.7, 34.5 and 57.0 mSv for the liver,
      intestines, spleen, kidneys and thyroid, respectively, and the effective dose was
      6.1 mSv. CONCLUSION: All absorbed doses were comparable to those known from most
      of the (99m)Tc studies. (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 obtained from kit
      formulations showed high tumour uptake in patients with malignant lesions, making
      it a promising imaging radiopharmaceutical for targeting site-specific breast
      cancer. The results obtained in this study warrant further clinical studies to
      determine the specificity and sensitivity of (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2.

PMID- 24335878
TI  - Radioguided parathyroidectomy in patients with secondary hyperparathyroidism due
      to chronic renal failure.
AB  - OBJECTIVE: The aim of the study was to determine the effectiveness of radioguided
      parathyroidectomy in patients with secondary hyperparathyroidism (sHPT) due to
      chronic renal failure (CRF). METHODS: Between August 2003 and October 2011, CRF
      patients undergoing parathyroidectomy for sHPT received conventional
      parathyroidectomy with preoperative ultrasound localization or radioguided
      surgery. For radioguided surgery, 370 MBq of (99m)Tc-sestamibi was injected
      intravenously 1.5-2 h before surgery, and a gamma probe was used intraoperatively
      to identify the parathyroid glands by radioactivity count. RESULTS: Twenty-five
      patients underwent conventional parathyroidectomy and 25 underwent radioguided
      parathyroidectomy. The median patient age was 55 years (range, 37-75 years). In
      the conventional surgery group, the parathyroid glands were removed in 18
      patients, and seven patients experienced recurrence as determined by intact
      parathyroid hormone (iPTH) levels. One patient in the radioguided surgery group
      experienced recurrence due to ectopic parathyroid tissue in the mediastinum. The
      operative time of radioguided surgery was shorter than that of conventional
      surgery [median (interquartile range), 100.0 (84.0-118.0) vs. 114.0 (103.0-134.0)
      min, respectively; P=0.015]. On postoperative day 1, iPTH and serum calcium
      levels were significantly lower in the radioguided surgery group than in the
      conventional surgery group [median (interquartile range), iPTH: 3 (3-20) vs. 53
      (11-230) ng/l; P=0.006, calcium: 1.72 (1.63-1.85) vs. 2.06 (1.92-2.12) mmol/l;
      P<0.001]. Radioactivity counts of parathyroid glands were significantly higher
      than in thyroid tissue, lymph nodes, and fat (all, P<0.001). CONCLUSION:
      Radioguided localization of the parathyroid glands improves the success rate of
      surgery in patients with CRF undergoing parathyroidectomy for sHPT.

PMID- 24335879
TI  - Calibrated image-derived input functions for the determination of the metabolic
      uptake rate of glucose with [18F]-FDG PET.
AB  - PURPOSE: We investigated the use of a simple calibration method to remove bias in
      previously proposed approaches to image-derived input functions (IDIFs) when used
      to calculate the metabolic uptake rate of glucose (K(m)) from dynamic [(18)F]-FDG
      PET scans of the thigh. Our objective was to obtain nonbiased, low-variance K(m)
      values without blood sampling. MATERIALS AND METHODS: We evaluated eight
      previously proposed IDIF methods. K(m) values derived from these IDIFs were
      compared with Km values calculated from the arterial blood samples (gold
      standard). We used linear regression to extract calibration parameters to remove
      bias. Following calibration, cross-validation and bootstrapping were used to
      estimate the mean square error and variance. RESULTS: Three of the previously
      proposed methods failed mainly because of zero-crossings of the IDIF. The
      remaining five methods were improved by calibration, yielding unbiased Km values.
      The method with the lowest SD yielded an SD of 0.0017/min--that is, below 10% of
      the muscle K(m) value in this study. CONCLUSION: Previously proposed IDIF methods
      can be improved by using a simple calibration procedure. The calibration
      procedure may be used in other studies, thus obviating the need for arterial
      blood sampling, once the calibration parameters have been established in a
      subgroup of participants. The method has potential for use in other parts of the
      body as it is robust with regard to partial volume effects.

PMID- 24335880
TI  - The evaluation of the influence of selected patellofemoral joint geometry
      indicators observed in magnetic resonance imaging on the incidence of anterior
      knee pain in patients after anterior cruciate ligament reconstruction using
      hamstrings.
AB  - BACKGROUND: Anterior knee pain (AKP) is a frequent serious clinical problem after
      anterior cruciate ligament (ACL) reconstruction, regardless of the graft material
      used. The author conducted prospective studies of the correlation between AKP and
      disturbed geometry of patello-femoral joint observed in magnetic resonance
      imaging (MRI), in patients with injured ACL reconstructed with the use of
      hamstrings. MATERIAL AND METHODS: The study included 60 patients (34 males and 26
      females), at the mean age of 31, who underwent ACL reconstruction with flexors.
      Only patients without clinical AKP symptoms or AKP factors after reconstruction
      were included in the study. Before surgery, in all patients MRI was performed in
      order to evaluate the patellar height, excessive patellar pressure (EPP) and
      patellar lateralization (PL). In the postoperative course, AKP and its
      correlation with the ratios mentioned above were observed. RESULTS: In the group
      of patients included in the study, pathological patellar height was not observed,
      EPP was diagnosed in 15%, PL in 13.3% and EPP and PL jointly in 11.9% of the
      patients. AKP was observed in 8 out of 9 patients with abnormal lateral pressure,
      7 patients with EPP and 7 patients with concomitant excessive lateral pressure
      and PL. The first symptoms of AKP appeared between the seventh and twelfth week
      after surgery and increased after 12 weeks. CONCLUSIONS: The occurrence of
      excessive lateral pressure syndrom (EPP) and PL confirmed in MRI was very
      strongly correlated (89% and 100%, respectively) with the occurrence of AKP after
      ACL reconstruction. The evaluation of the patellofemoral joint geometry, taking
      into account the EPP and PL ratios in pre-operative magnetic resonance image
      (MRI) in patients with injured anterior cruciate ligament, may allow us to
      establish the AKP risk group and administer suitable preventive treatment
      (prophylaxis).

PMID- 24335882
TI  - Metabolic syndrome and arterial stiffness: the past, the present and the future.

PMID- 24335884
TI  - Valvular manifestations of human immunodeficiency virus infection--results from
      the prospective, multicenter HIV-HEART study.
AB  - BACKGROUND AND AIMS: HIV infection is associated with an elevated rate of cardiac
      diseases. The aim of the current study was to assess the prevalence of valvular
      disorders in a large population of HIV-infected patients. METHODS: We enrolled
      803 adults (age 44 +/- 10 years, 16.6% women) in this prospective, multicenter
      cohort study. All patients underwent a comprehensive two-dimensional
      transthoracic echocardiography examination including Doppler evaluation of
      valvular function. Statistical analyses were performed in respect of severity of
      HIV infection. RESULTS: Overall, the rate of patients with pathologic function of
      cardiac valves was 77.6% (N = 623). Most of these patients had signs of valvular
      regurgitation (N = 620; 77.2%), whereas stenoses were rare (N = 23; 2.9%).
      Clinically relevant valvular disorders (excluding mild stages) were seen in only
      4.7% (N = 38; regurgitation: N = 36, 4.5%; stenosis: N = 3, 0.4%). Clinical
      stages of HIV infection, defined by the Centers for Disease Control and
      Prevention (CDC) classification, were associated with higher rates of valvular
      diseases (CDC-stage B/C versus A: 6.2 versus 2.3%, P = 0.015). However, there was
      no association between current CD4 cell count or virus load and the prevalence of
      valvular disorders (both P > 0.2). None of the patients had signs of active
      endocarditis in the present study. CONCLUSION: Valvular heart diseases are common
      in HIV-infected patients. Fortunately, most of these disorders are mild today. We
      found an association between the onset of valvular heart disease and clinical
      stages of HIV infection.

PMID- 24335883
TI  - The impact of training on diagnostic accuracy with computed tomography coronary
      angiography.
AB  - AIM: The aim of this study is to assess the image quality and diagnostic accuracy
      of computed tomography (CT) coronary angiography (CTCA) in different hospital
      settings with the same trained team. MATERIALS AND METHODS: Four hundred patients
      were consecutively enrolled for CTCA in a large academic hospital (Group 1;
      Sensation 64 Cardiac, Siemens - Iomeprol 400, Bracco; 200 patients) and in a
      small local hospital (Group 2; VCT, GE Healthcare - Iodixanol 320, GE Healthcare;
      200 patients). All patients were enrolled for suspected coronary artery disease
      (CAD) and patients with stents or who had previously undergone coronary bypass
      were excluded. Scan protocols (retrospectively ECG-gated; no dose reduction
      modulation applied) were performed in accordance with standards reported in the
      international literature with the best solution available on site. Image quality
      was assessed in each coronary segment with a 4-point Likert scale: 0, not
      assessable; 1, low; 2, average; 3, good. Diagnostic accuracy was calculated
      against conventional coronary angiography with a threshold of at least 50% for
      significant stenosis. RESULTS: There was no significant difference between
      demographics, BMI, prevalence of obstructive CAD, calcium score and heart rate
      between the two populations. The average image quality was 2.83 +/- 0.37 for
      Group 1 and 2.86 +/- 0.31 for Group 2 (P > 0.05). Per-segment sensitivity,
      specificity, positive and negative predictive values were 92.6% (87-95), 97.9%
      (97-98), 75.9% (69-81) and 99.5% (99-99), respectively, for Group 1, and 90.4%
      (85-93), 98.6% (98-99), 84.2% (78-88) and 99.2% (98-99), respectively, for Group
      2 (P > 0.05). CONCLUSION: There is no significant difference in image quality and
      diagnostic accuracy of CTCA when the investigation is performed by the same
      properly trained team. CTCA is a robust imaging modality for the detection of
      coronary artery stenosis.

PMID- 24335885
TI  - Routine evaluation of abdominal aorta diameter at the end of transthoracic
      echocardiography in hypertensive patients. Why not?

PMID- 24335886
TI  - Task force on: 'Early markers of atherosclerosis: influence of age and sex'.
AB  - Atherosclerosis and its complications are the most important causes of death all
      over the world, especially in Western countries. Diet habits, modern stress life,
      smoking, sedentary way of life and an involvement of genetic pattern of
      individuals lead to a sure degeneration of quality of life increasing the risk of
      atherosclerosis development. For this reason, the main purpose of actual medicine
      is to identify all the markers that could allow the physicians to evaluate the
      first moments of the development of this dangerous pathological process. The aim
      is to reduce the speed of its evolution, trying to delay indefinitely the risk
      coming from the morphological alterations of the vessels. 'Endothelium function'
      could allow physicians to detect the first moment of the natural history of
      atherosclerosis process. Its impairment is the first step in the degeneration of
      vascular structures. Many methods [flow-mediated vasodilatation (FMD); antero
      posterior abdominal aorta diameter (APAO); intima-media thickness of the common
      carotid artery (CCA-IMT); arterial stiffness; and so on] try to evaluate its
      function, but many limitations come from general population characteristics. A
      standardization of the methods should take into account individuals'
      peculiarities. Two elements, not modifiable, should be taken into account for
      vascular evaluation: age and sex. The aim of this review is to outline the
      linkage among age, sex and instrumental evaluation of patients considered for a
      noninvasive assessment of their cardiovascular risk profile.

PMID- 24335887
TI  - Updates on the treatment of human epidermal growth factor receptor type 2
      positive breast cancer.
AB  - PURPOSE OF REVIEW: To review the most recent developments in the treatment of
      human epidermal growth factor receptor type 2 (HER2)-positive breast cancer with
      novel HER2-targeting agents and combinations that have significantly improved
      clinical outcomes. RECENT FINDINGS: Since the approval of trastuzumab 15 years
      ago, the natural history of HER2-positive breast cancer has been altered with
      improvements in survival for both early and advanced disease with the addition of
      this agent to standard chemotherapy. The HER2 receptor pathway drives breast
      cancer growth and aggressiveness, and HER2-targeted agents can improve survival
      in early and advanced disease. In the advanced setting, two new drugs have been
      approved since 2012, pertuzumab and ado-trastuzumab emtansine (T-DM1), both of
      which improve survival without any reciprocal increase in toxicity. However,
      resistance almost always ensues, pointing to the need to understand the driving
      mechanisms and to biomarkers that will help individualize therapy and point to
      newer signal transduction and other modulators. SUMMARY: HER2-positive breast
      cancer represents a distinct subtype with more aggressive clinical
      characteristics. HER2-targeted therapies, usually in combination with
      chemotherapy, are the standard of care, improving the cure rate in early-stage
      breast cancer and lengthening survival in the advanced setting.

PMID- 24335888
TI  - Ginzburg-Landau-type theory of spin superconductivity.
AB  - Spin superconductivity is a recently proposed analogue of conventional charge
      superconductivity, in which spin currents flow without dissipation but charge
      currents do not. Here we derive a universal framework for describing the
      properties of a spin superconductor along similar lines to the Ginzburg-Landau
      equations that describe conventional superconductors, and show that the second of
      these Ginzburg-Landau-type equations is equivalent to a generalized London
      equation. Just as the GL equations enabled researchers to explore the behaviour
      of charge superconductors, our Ginzburg-Landau-type equations enable us to make a
      number of non-trivial predictions about the potential behaviour of putative spin
      superconductor. They enable us to calculate the super spin current in a spin
      superconductor under a uniform electric field or that induced by a thin
      conducting wire. Moreover, they allow us to predict the emergence of new
      phenomena, including the spin-current Josephson effect in which a time
      independent magnetic field induces a time-dependent spin current. 

PMID- 24335889
TI  - Alkylating agents induce histone H3K18 hyperacetylation and potentiate HDAC
      inhibitor-mediated global histone acetylation and cytotoxicity in mantle cell
      lymphoma.

PMID- 24335890
TI  - Mightier than the sword...

PMID- 24335891
TI  - Negative pressure wound therapy: improving the patient experience part 3 of 3.
AB  - Negative pressure wound therapy (NPWT) is considered to be an effective wound
      treatment, yet research has highlighted a clear need for its improvement,
      particularly in reducing pain. This is important not only for patient well-being
      and treatment satisfaction but also for the healing process. In parts 1 and 2,
      wound care clinicians were invited to share their views on patients' experiences
      of NPWT. Part 3, presented here, explores the views of patients who have had
      NPWT, through use of a questionnaire survey and interview (n = 50). Findings show
      that the majority of patients felt that NPWT had a positive impact on their wound
      (94%) and that their overall experience was positive (88%). However, respondents
      identified a number of challenges associated with NPWT, such as reduced mobility,
      noise issues, and sleep disturbance. Respondents also identified a number of
      areas for improvement with NPWT, including greater training for nurses, practical
      alterations to the equipment, and methods of minimising pain and skin damage
      during NPWT. Taken together with the findings from part one and two, this study
      highlights several key considerations for future research and clinical practice
      with NPWT. 

PMID- 24335892
TI  - An experience with paediatric burn wounds treated with a plant-derived wound
      therapeutic.
AB  - OBJECTIVE: To observe the efficacy of a plant-derived wound dressing (1 Primary
      Wound Dressing(r)), a mixture of hypericum and neem oil, in different types of
      paediatric burns. METHOD: A retrospective review was conducted over the complete
      healing course of 9 paediatric patients with a mean age of 8.17+/-3.35 (1-11
      years), presenting mixed, partial or full-thickness burns. The treatment applied
      by the wound care specialist consisted of daily cleansing of the wound with a
      saline solution and application of 1 Primary Wound Dressing on the whole wound
      surface. There was no application of a secondary dressing. The time to heal,
      wound size, ease of handling, pain and complications were recorded. Procedural
      and background pain were observed in six of the patients older than 5 years (mean
      age 9.6+/-2.39, range 8-11 years). Due to the small number of patients examined
      during the period studied, it was not possible to perform statistical analyses.
      RESULTS: The mean wound size was 50.76+/-48.32cm2 (4.63-132.0cm2). A rapid
      induction of granulation tissue and re-epithelialisation was observed. Time to
      complete healing was 16.6+/-4.69 days (10-22 days). No complications related to
      wound infection was observed. The 6 patients older than five years reported a
      strong relief of pain, from an initial value of 7-8 out of 10 to 0 out of 10
      within the first week of treatment. This remained at the 0 out of 10 level during
      the second and third weeks of treatment. CONCLUSION: This retrospective, non
      controlled examination suggests that 1 Primary Wound Dressing could be an
      effective therapy for the treatment of burn wounds, with benefits including pain
      reduction and simplicity of use. Further evaluations with a larger population are
      required to document the effectiveness of this plant-derived wound dressing in a
      controlled fashion. DECLARATION OF INTEREST: There were no external sources of
      funding for this study. F. Carnevali is a researcher and co-inventor of 1 Primary
      Wound Dressing(r).

PMID- 24335893
TI  - Development of an algorithm as an implementation model for a wound management
      formulary across a UK health economy.
AB  - This article outlines a strategic process for the evaluation of wound management
      products and the development of an algorithm as an implementation model for wound
      management. Wound management is an increasingly complex process given the variety
      of interactive dressings and other devices available. This article discusses the
      procurement process, access to wound management dressings and the use of wound
      management formularies within the UK. We conclude that the current commissioners
      of tissue viability within healthcare organisations need to adopt a proactive
      approach to ensure appropriate formulary evaluation and product selection, in
      order to achieve the most beneficial clinical and financial outcomes. 

PMID- 24335894
TI  - Superior gluteal artery perforator flap: a reliable method for sacral pressure
      ulcer reconstruction.
AB  - OBJECTIVE: To study the feasibility and reliability of the superior gluteal
      artery perforator (SGAP) flap for the reconstruction of sacral pressure ulcers.
      METHOD: A prospective study was conducted between 2009 and 2012 where a total of
      15 patients with sacral pressure ulcers underwent reconstructive surgery with an
      islanded pedicled SGAP flap. Success of the flap reconstruction and primary
      healing were defined as a healed wound within 30 days of the procedure.
      Reconstructive failure was defined as those cases that resulted in a non-healed
      wound, thereafter. RESULTS: Of the 15 patients in the evaluation, 12 were male
      and 3 were female. Eleven patients were paraplegic, 3 were ambulatory and one was
      quadriplegic. All reconstructed flaps survived completely with no mortality or
      major donor site complications. Three patients had a minor infection and wound
      dehiscence that healed spontaneously. All wounds healed within 30 days of surgery
      following local wound care and culture-sensitive antibiotics. No recurrence of
      the pressure ulcer occurred during follow-up. The non-paraplegic patients did not
      develop gait disturbances following the surgery. CONCLUSION: These observations
      suggest that the islanded pedicled SGAP fasciocutaneous flap is a relatively easy
      flap to raise, with good reliability and minimal complications, and is therefore
      highly recommended for the reconstruction of the sacral pressure ulcer.
      DECLARATION OF INTEREST: There were no external sources of funding for this
      study. The authors have no conflicts of interest to declare.

PMID- 24335895
TI  - Use of acellular dermal regeneration template combined with NPWT to treat
      complicated extremity wounds in children.
AB  - OBJECTIVE: The treatment of open wounds with exposed bone, tendon, or nerve is a
      challenging reconstructive problem, especially in children. The purpose of this
      study is to evaluate the safety and effectiveness of using acellular dermal
      templates combined with negative pressure wound dressings in the treatment of
      complicated paediatric soft tissue extremity wounds. METHOD: A retrospective
      review of eight patients treated with acellular dermal templates for closure of
      complicated extremity wounds was performed. After debridement, all patients were
      treated with a template and a negative pressure wound treatment (NPWT) system.
      RESULTS: The average age was 8.8 years with 4 females and 4 males. Four wounds
      were at the foot/ankle, with tendon exposed in all 4, nerve in 2, and bone in 3.
      There were 3 lower leg wounds, all with exposed bone. One patient had arm/hand
      wounds with exposed tendon. The size of the wounds and dermal graft averaged
      86cm2 and 57cm2. The average time to wound closure was 65 days. The majority of
      the treatment was received as an outpatient, including NPWT. For inpatient and
      outpatient care, the average number of sponge system changes was 2.6 compared to
      4.6, and time between changes was 3.5 compared to 6.8 days. Each patient had only
      one procedure each for application of the dermal substitute and later one skin
      grafting procedure. Complications were minimal, and all patients healed their
      wounds without the need of flaps. One patient required wound revision.
      CONCLUSION: Our study demonstrates that a dermal template combined with NPWT can
      safely and effectively be used to treat complicated wounds in children. Closure
      was obtained without flaps, the majority of the treatment time was spent in the
      outpatient setting, and the complication rate was low. DECLARATION OF INTEREST:
      There were no external sources of funding for this study. The authors have no
      conflicts of interest to declare.

PMID- 24335896
TI  - Predictors of neighborhood risk for late-stage melanoma: addressing disparities
      through spatial analysis and area-based measures.
AB  - Minority populations have disproportionately more advanced stage melanoma and
      worse survival. To clarify the impact of race and ethnicity on late-stage
      melanoma diagnosis, we performed spatial analysis of geocoded melanoma cases
      diagnosed in Florida, 1999-2008, to identify geographic clusters of higher-than
      expected incidence of late-stage melanoma and developed predictive models for
      melanoma cases in high-risk neighborhoods accounting for area-based poverty,
      race/ethnicity, patient insurance status, age, and gender. In the adjusted model,
      Hispanic ethnicity and census tract-level poverty are the strongest predictors
      for clustering of late-stage melanoma. Hispanic whites were 43% more likely to
      live in neighborhoods with excessive late-stage melanoma (P<0.001) compared with
      non-Hispanic whites (NHW). For every 1% increase in population living in poverty,
      there is a 2% increase in late-stage melanoma clustering (P<0.001). Census tract
      level poverty predicted late-stage melanoma similarly among NHW and Hispanic
      whites. The impact of insurance coverage varied among populations; the most
      consistent trend was that Medicaid coverage is associated with higher odds for
      late-stage melanoma. The finding that Hispanics are most likely to reside in high
      risk neighborhoods, independent of poverty and insurance status, underscores the
      importance of addressing, and overcoming community-level barriers to melanoma
      care. 

PMID- 24335897
TI  - p16INK4A influences the aging phenotype in the living skin equivalent.

PMID- 24335898
TI  - Melanocytes are selectively vulnerable to UVA-mediated bystander oxidative
      signaling.
AB  - Long-wave UVA is the major component of terrestrial UV radiation and is also the
      predominant constituent of indoor sunlamps, both of which have been shown to
      increase cutaneous melanoma risk. Using a two-chamber model, we show that UVA
      exposed target cells induce intercellular oxidative signaling to non-irradiated
      bystander cells. This UVA-mediated bystander stress is observed between all three
      cutaneous cell types (i.e., keratinocytes, melanocytes, and fibroblasts).
      Significantly, melanocytes appear to be more resistant to direct UVA effects
      compared with keratinocytes and fibroblasts, although melanocytes are also more
      susceptible to bystander oxidative signaling. The extensive intercellular flux of
      oxidative species has not been previously appreciated and could possibly
      contribute to the observed cancer risk associated with prolonged UVA exposure. 

PMID- 24335899
TI  - Fibronectin at select sites binds multiple growth factors and enhances their
      activity: expansion of the collaborative ECM-GF paradigm.
AB  - Intensive research has demonstrated that extracellular matrix (ECM) molecules and
      growth factors (GF) collaborate at many different levels. The ability of ECM to
      modulate GF signals has important implications in tissue formation and
      homeostasis as well as novel therapies for acute and chronic wounds. Recently, a
      number of GF-binding sites was identified in fibronectin (FN) and was shown to
      provide another layer of regulation on GF signaling. Here, we review these new
      findings on FN interaction with GF in the context of general ways ECM molecules
      regulate GF signaling. 

PMID- 24335900
TI  - Modeling MC1R rare variants: a structural evaluation of variants detected in a
      Mediterranean case-control study.

PMID- 24335901
TI  - Reduced MiR-675 in exosome in H19 RNA-related melanogenesis via MITF as a direct
      target.
AB  - H19 non-coding RNA downregulation stimulates melanogenesis in melasma patients.
      However, its mechanism is unclear. In this study, the potential role of a H19
      microRNA, miR-675, in melanogenesis was examined. Real-time PCR using cultured
      normal human skin keratinocytes, melanocytes, and fibroblasts with or without H19
      knockdown showed accompanying changes between expression levels of H19 and those
      of miR-675 in keratinocytes. MiR-675 was also detected in concentrated culture
      supernatants and showed expression levels parallel with those of cell lysates. In
      addition to RNase resistance, FACS analysis showed anti-CD63-positive exosomes in
      culture supernatants, suggesting miR-675 could be released extracellularly and
      delivered to neighboring cells without degradation. In western blot analysis, the
      miR-675 mimic reduced the expression of microphthalmia-associated transcription
      factor (MITF) and phosphorylation of cAMP-responsive element-binding protein,
      extracellular signal-regulated kinase and apoptosis signal-regulating kinase,
      whereas these expressions were increased by the miR-675 inhibitor. Although H19
      was not a miR-675 target, luciferase reporter assay showed a direct binding of
      miR-675 to 3'-untranslated region of MITF. In addition, localized in vivo miR-675
      overexpression in mouse using a cationic polymer transfection reagent showed
      reduced mRNA expression levels of MITF, tyrosinase, tyrosine-related protein-1
      (Trp-1), and Trp-2. Collectively, the results suggest that miR-675 derived from
      keratinocytes could be involved in H19-stimulated melanogenesis using MITF as a
      target of miR-675. 

PMID- 24335902
TI  - IL-17 T cells' defective differentiation in vitro despite normal range ex vivo in
      chronic mucocutaneous candidiasis due to STAT1 mutation.

PMID- 24335903
TI  - Liver function breath tests for differentiation of steatohepatitis from simple
      fatty liver in patients with nonalcoholic Fatty liver disease.
AB  - GOALS: We investigated the utility of liver function breath tests [C-Aminopyrine
      Breath Test (C-ABT), C-Galactose Breath Test (C-GBT)], for the diagnosis of
      nonalcoholic steatohepatitis (NASH) among nonalcoholic fatty liver disease
      (NAFLD) patients. BACKGROUND: Liver biopsy is currently the gold standard for the
      differentiation between simple fatty liver (NAFL) and NASH in NAFLD patients.
      MATERIALS AND METHODS: Thirty-six patients with histologically proven NAFLD
      (NAFL:16, NASH:20) underwent C-ABT and C-GBT. The results were expressed as the
      percentage of administered C dose recovered per hour (%dose/h) and as cumulative
      percentage of administered C dose recovered over time (%cumulative dose).
      Histologic lesions were scored according to Brunt and Kleiner's classifications.
      RESULTS: C-ABT results correlated inversely with activity grade (r=-0.650,
      P=0.001), NAFLD activity score (r=-0.473, P=0.026), and fibrosis stage (r=-0.719,
      P=0.001). Compared with NAFL, NASH patients had significantly lower %dose/h and
      %cumulative dose at 60, 90, and 120 minutes (always P<0.04) by C-ABT. C-ABT
      %dose/h and %cumulative dose at 120 minutes could predict the presence of NASH
      (area under the receiver operating characteristic curve: 0.762 and 0.741,
      respectively). In contrast, there was no significant association between C-GBT
      results and any patient characteristic. CONCLUSIONS: In the NAFLD patients,
      decreased and delayed liver microsomal function, as assessed by C-ABT, is
      associated with more severe necroinflammation and fibrosis, whereas C-ABT results
      at 120 minutes may be helpful for the diagnosis of NASH.

PMID- 24335904
TI  - In response.

PMID- 24335905
TI  - 12 years innovation and inclusion.

PMID- 24335906
TI  - Wnt5a uses CD146 as a receptor to regulate cell motility and convergent
      extension.
AB  - Dysregulation of Wnt signalling leads to developmental defects and diseases. Non
      canonical Wnt signalling via planar cell polarity proteins regulates cell
      migration and convergent extension; however, the underlying mechanisms are poorly
      understood. Here we report that Wnt5a uses CD146 as a receptor to regulate cell
      migration and zebrafish embryonic convergent extension. CD146 binds to Wnt5a with
      the high affinity required for Wnt5a-induced activation of Dishevelled (Dvl) and
      c-jun amino-terminal kinase (JNK). The interaction between CD146 and Dvl2 is
      enhanced on Wnt5a treatment. Mutation of the Dvl2-binding region impairs its
      ability to activate JNK, promote cell migration and facilitate the formation of
      cell protrusions. Knockdown of Dvls impairs CD146-induced cell migration.
      Interestingly, CD146 inhibits canonical Wnt signalling by promoting beta-catenin
      degradation. Our results suggest a model in which CD146 acts as a functional
      Wnt5a receptor in regulating cell migration and convergent extension, turning off
      the canonical Wnt signalling branch. 

PMID- 24335907
TI  - A current model of neural circuitry active in forming mental images.
AB  - My aim here is to formulate a compact, intuitively understandable model of neural
      circuits active in imagination that would be consistent with the current state of
      knowledge, but that would be simple enough to be able to use for teaching. I
      argue that such a model should be based on the recent idea of "concept neurons"
      and circuits of 2 separate loops necessary for recalling mental images and
      consolidation of memory traces of long-term memory. This paper discusses the role
      of the hippocampus and temporal lobe, emphasizing the essential importance of
      recurrent pathways and oscillations occurring in the upper layers of hierarchical
      neural structures, as well as oscillations in thalamo-cortical loops. The
      elaborated model helps explain specific processes such as imagining future
      situations, novel objects, and anticipated action, as well as imagination
      concerning oneself, which is indispensable for the sense of identity and self
      awareness. I attempt to present this compact, simple model of neural circuitry
      active in imagination by using some intuitive, demonstrative figures. 

PMID- 24335908
TI  - Duplicate publications and salami reports: corruption of the scientific record.

PMID- 24335909
TI  - Adaptation of a communication interaction behavior instrument for use in
      mechanically ventilated, nonvocal older adults.
AB  - BACKGROUND: Valid and reliable instruments are needed to measure communication
      interaction behaviors between nurses and mechanically ventilated intensive care
      unit patients who are without oral speech. OBJECTIVES: The aim of this study was
      to refine and evaluate preliminary validity and reliability of a Communication
      Interaction Behavior Instrument (CIBI) adapted for use with mechanically
      ventilated, nonvocal patients in the intensive care unit. METHODS: Raters
      observed nurse-patient communication interactions using a checklist of nurse and
      patient behaviors, categorized as positive and negative behaviors. Three-minute
      video-recorded observations of five mechanically ventilated adults (<60 years
      old) in the intensive care unit and their nurses were used to establish
      preliminary interrater reliability and confirm appropriateness of definitions
      (four observations per dyad, n = 20). On the basis of expert input and
      reliability results, the behaviors and item definitions on the CIBI were revised.
      The revised tool was then tested in a larger sample of 38 mechanically ventilated
      intensive care patients (> 60 years old) and their nurses (four observations per
      dyad, n = 152) to determine interrater reliability. RESULTS: For preliminary
      testing, percent agreement for individual items ranged from 60% to 100% for nurse
      behaviors and 20% to 100% for patient behaviors across the five pilot cases. On
      the basis of these results, 11 definitions were modified and four items were
      dropped. Using the revised 29-item instrument, percent agreement improved for
      nurse behaviors (73%-100%) and patient behaviors (68%-100%). Kappa coefficients
      ranged from 0.13 to 1.00, with lower coefficients for patient behaviors.
      CONCLUSION: Preliminary results suggest that the revised CIBI has good face
      validity and shows good interrater reliability for many of the behaviors, but
      further refinement is needed. The use of dual raters with adjudication of
      discrepancies is the recommended method of administration for the revised CIBI.

PMID- 24335910
TI  - "Great expectations" of adoptive parents: theory extension through structural
      equation modeling.
AB  - BACKGROUND: Most of the 2 million adoptive parents in the United States make the
      transition to parenting successfully. Adoptive parents who do not make the
      transition easily may put their children at risk for negative outcomes.
      OBJECTIVES: The aim of this study was to further refine Foli's midrange theory of
      postadoption depression, which postulates that fulfillment of expectations is a
      principal contributor to parental emotional health status, aggravation, and
      bonding. METHODS: The linked dataset (National Survey of Children's Health and
      National Survey of Adoptive Parents) was used for structural equation modeling.
      The sample consisted of 1,426 parents with adopted children who had been placed
      in the home more than 2 years before survey completion. RESULTS: Special services
      and child's behaviors were direct determinants of parental expectations, and
      parental expectations were direct determinants of parental aggravation and
      parentalbonding. As anticipated, parental expectations served as a mediator
      between child-related variables and parental outcomes. A path was also found
      between child's behaviors and special services and parental emotional health
      status. Child's past trauma was also associated with parental bonding.
      DISCUSSION: Parental expectations showed direct relationships with the latent
      variables of parental aggravation and bonding. Future research should examine
      factors associated with early transition when children have been in the adoptive
      home less than 2 years and include specific expectations held by parents.

PMID- 24335911
TI  - Quality of reporting randomized controlled trials in cancer nursing research.
AB  - BACKGROUND: Results of randomized controlled trials (RCTs) provide high-level
      evidence for evidence-based practice (EBP). The quality of RCTs has a substantial
      influence on providing reliable knowledge for EBP. Little is known about the
      quality of RCT reporting in cancer nursing. OBJECTIVE: The aim of this study was
      to assess the quality of reporting in published cancer nursing RCTs from 1984 to
      2010. METHODS: A total of 227 RCTs in cancer nursing published in English
      language journals and indexed in PubMed or Cumulative Index to Nursing and Allied
      Health Literature were reviewed using the Jadad scale, key methodologic index
      (KMI), and the Consolidated Standards of Reporting Trials (CONSORT) checklist to
      assess the quality of reporting methodological aspects of research and the
      overall quality of reporting RCTs. RESULTS: Adherence to reporting metrics was
      relatively low, based on the Jadad score (M = 1.94 out of 5, SD = 1.01), KMI
      scores (M = 0.84 out of 3, SD = .87), and adherence to CONSORT checklist items (M
      =16.92 out of 37, SD = 4.03). Only 11 of 37 items in the CONSORT checklist were
      reported in 80% or more of the studies reviewed. The quality of reporting showed
      some improvement over time. DISCUSSION: Adherence to reporting metrics for cancer
      nursing RCTs was suboptimal, and further efforts are needed to improve both
      methodology reporting and overall reporting. Journals are encouraged to adopt the
      CONSORT checklist to influence the quality of RCT reports.

PMID- 24335913
TI  - The association of pain with protein inflammatory biomarkers: a review of the
      literature.
AB  - BACKGROUND: Pain is a key diagnostic criterion in many medical conditions. In the
      absence of self-reported pain, measurement of a proxy for pain, such as an
      inflammatory biomarker, could aid in diagnosis and disease management.
      OBJECTIVES: The aim was to determine if there is an association between
      inflammatory biomarkers and self-reported pain in individuals with medical
      conditions associated with the symptom of pain and to clarify whether
      inflammatory biomarkers might aid in the diagnostic process. METHODS: An
      integrative literature review was conducted. PubMed, CINAHL, and Cochrane
      databases were searched for articles published between January 2000 and September
      2012. Inclusion criteria were original research testing a relationship between
      inflammatory biomarkers and pain, pain measurement, laboratory measure of
      inflammatory biomarkers, and a prospective single-group experimental design or
      comparative nonrandomized or randomized design. Excluded were studies describing
      an association between inflammatory biomarkers and treatment, risk, and
      generation; pathophysiology; or genetic polymorphisms/transcripts. Ten studies
      meeting inclusion criteria were reviewed. RESULTS: In most of the studies,
      baseline elevations in both proinflammatory and anti-inflammatory cytokines were
      reported in painful conditions compared with healthy controls. In half of the
      studies, higher levels of proinflammatory markers (C-reactive protein, tumor
      necrosis factor-alpha, interleukin-2 [IL-2], IL-6, IL-8, IL-10, and CD40 ligand)
      were associated with greater pain. Proinflammatory cytokines decreased after
      treatment for pain in only two studies. DISCUSSION: The association between
      inflammatory markers varied in the direction and magnitude of expression, which
      may be explained by differences in designs and assays, disease condition and
      duration, variations in symptom severity, and timing of measurement. Elevation in
      anti-inflammatory cytokines in the presence of pain represents a homeostatic
      immune response. Further study is required to determine the value of cytokines as
      biomarkers of pain.

PMID- 24335912
TI  - An integrative review of factors associated with telomere length and implications
      for biobehavioral research.
AB  - BACKGROUND: Although telomere shortening occurs as a natural part of aging, there
      is now a robust body of research that suggests that there is a relationship
      between psychosocial, environmental, and behavioral factors and changes in
      telomere length. These factors need to be considered when integrating telomere
      measurement in biobehavioral research studies. OBJECTIVES: This article provides
      a brief summary of the known facts about telomere biology and an integrative
      review of current human research studies that assessed relationships between
      psychosocial, environmental, or behavioral factors and telomere length. METHODS:
      An integrative review was conducted to examine human research studies that
      focused on psychosocial, environmental, and behavioral factors affecting telomere
      length and telomerase activity using the electronic databases PubMed/Medline and
      CINAHL from 2003 to the present. In addition to the known individual factors that
      are associated with telomere length, the results of the integrative review
      suggest that perceived stress, childhood adversities, major depressive disorder,
      educational attainment, physical activity, and sleep duration should also be
      measured. DISCUSSION: Multiple factors have been shown to affect telomere length.
      To advance understanding of the role of telomere length in health and disease
      risk, it will be important to further elucidate the mechanisms that contribute to
      telomere shortening.

PMID- 24335914
TI  - Costs associated with recruitment and interviewing of study participants in a
      diverse population of community-dwelling older adults.
AB  - BACKGROUND: America's racial and ethnic composition is changing so rapidly that
      minority groups are expected to constitute almost half of the U.S. population by
      2060. Special efforts are needed to effectively recruit and retain members of
      racial and ethnic minority groups in health-related research studies, but the
      information available on time and costs associated with their recruitment is
      limited. OBJECTIVES: The aim of this study was to describe and compare the time
      and monetary costs associated with recruiting and interviewing a diverse sample
      of older adults living in south Florida. METHODS: Men and women aged 60 years and
      older from four ethnic groups-African American, Afro-Caribbean, Hispanic
      American, and European American-were recruited to participate in a longitudinal
      study of healthy aging. Costs for study activities (including recruitment,
      scheduling sessions, interviewing, file scoring, log updating, blood specimen
      analysis and storage, data analysis, and monetary compensation to participants)
      were determined after 100 weeks of data collection. RESULTS: Altogether, 483
      participants completed the study in the first 100 weeks. The total cost for each
      participant ranged from $265 to $576. Each successful enrollment required an
      average of 1.83 hours for recruitment and scheduling of the interviews. The time
      to interview African American and Afro-Caribbeans was greater than the time
      needed to interview Hispanic American and European American participants.
      DISCUSSION: To develop more accurate budgets for recruitment of minority
      individuals into research studies and to use the limited resources in an
      effective way, careful planning and ongoing monitoring of costs are essential.

PMID- 24335915
TI  - Errors in preparation and administration of insulin in two urban Vietnamese
      hospitals: an observational study.
AB  - BACKGROUND: Medication errors involving insulin are common, particularly during
      the administration stage, and may cause severe harm. Little is known about the
      prevalence of insulin administration errors in hospitals, especially in resource
      restricted settings, where the burden of diabetes is growing alarmingly.
      OBJECTIVES: The aim of this study was to determine the prevalence, type, and
      potential clinical outcome of errors in preparation and administration of insulin
      in resource-restricted setting hospitals. METHODS: This study was conducted on
      six wards in two urban public hospitals in Vietnam using a direct observation
      method. Details of insulin preparation and administration were collected by
      pharmacy students 12 hours per day for 7 consecutive days on each ward. Potential
      clinical outcome was judged by a panel of four experts using a validated scale.
      RESULTS: The error rate was 28.8% (95% confidence interval [23.1%, 35.2%], n = 66
      out of 229 insulin doses)-all with potentially moderate/severe outcome. Higher
      error rates were observed for infusion doses than for subcutaneous ones (80.0%
      vs. 22.5%, p < .01). Incorrect time, incorrect preparation/administration
      technique, and omissions were mostly encountered. DISCUSSION: Interventions
      suitable for resource-restricted settings need to be developed and tested to
      improve insulin preparation and administration, probably starting with education
      and providing information, especially infusion doses.

PMID- 24335916
TI  - What is the evidence for the use of mucosal flaps in Draf III procedures?
AB  - PURPOSE OF REVIEW: Recent literature has described the use of mucosal grafts or
      transplants to reduce the rate of frontal ostium restenosis after the endoscopic
      modified Lothrop procedure. This article presents a review of the literature on
      the rates of revision and restenosis related to Draf III procedures, factors
      implicated in the causation of restenosis and the evidence to support the role of
      mucosal grafts in reducing restenosis rates. RECENT FINDINGS: Compared to
      historic data and to the meta-analysis data by Anderson and Sindwani, results
      from three case series examining the use of mucosal flaps after endoscopic
      modified Lothrop procedure look extremely promising compared to a baseline
      average stenosis rate of 19% and revision rate of 14% quoted in the literature.
      SUMMARY: Although the concept appears sound in principle and the limited series
      published show potential reduction in revision rates, there is inadequate
      evidence to state conclusively that this technique will improve the results of
      Draf III procedures in all surgical hands.

PMID- 24335917
TI  - Assistance in dying for older people without a serious medical condition who have
      a wish to die: a national cross-sectional survey.
AB  - BACKGROUND: The Dutch euthanasia law regulates physician assistance in dying for
      patients who are suffering unbearably from a medical condition. We studied the
      attitudes of the Dutch population to assistance in dying for older persons who
      have a wish to die without the presence of a serious medical condition. METHODS:
      A cross-sectional survey was conducted among a random sample of the Dutch public
      (response rate 78%, n=1960), using statements and vignettes about attitudes to
      assistance in dying for older persons who are tired of living. RESULTS: A
      minority of 26% agreed with a vignette in which a physician warrants the request
      for physician-assisted suicide of an older person who is tired of living without
      having a serious medical condition. Furthermore, 21% agreed with the statement
      'In my opinion euthanasia should be allowed for persons who are tired of living
      without having a serious disease'. People supporting euthanasia for older persons
      who are tired of living were more likely than opponents to be highly educated (OR
      1.6; 95% CI 1.1 to 2.3), to be non-religious (OR 1.7; 95% CI 1.3 to 2.3), to have
      little trust in physicians (OR 1.6; 95% CI 1.2 to 2.2), and to prefer to make
      their own healthcare decisions (OR 1.7; 95% CI 1.3 to 2.3). CONCLUSIONS: Although
      it is lower than the level of support for assistance in dying for patients whose
      suffering is rooted in a serious medical condition, our finding that a
      substantial minority of the general public supports physician assistance in dying
      for older people who are tired of living implies that this topic may need to be
      taken seriously in the debate about end-of-life decision-making.

PMID- 24335918
TI  - A general approach to crystalline and monomodal pore size mesoporous materials.
AB  - Mesoporous oxides attract a great deal of interest in many fields, including
      energy, catalysis and separation, because of their tunable structural properties
      such as surface area, pore volume and size, and nanocrystalline walls. Here we
      report thermally stable, crystalline, thermally controlled monomodal pore size
      mesoporous materials. Generation of such materials involves the use of inverse
      micelles, elimination of solvent effects, minimizing the effect of water content
      and controlling the condensation of inorganic frameworks by NO(x) decomposition.
      Nanosize particles are formed in inverse micelles and are randomly packed to a
      mesoporous structure. The mesopores are created by interconnected intraparticle
      voids and can be tuned from 1.2 to 25 nm by controlling the nanoparticle size.
      Such phenomena allow the preparation of multiple phases of the same metal oxide
      and syntheses of materials having compositions throughout much of the periodic
      table, with different structures and thermal stabilities as high as 800  degrees
      C.

PMID- 24335919
TI  - The emerging problem of biological treatment in migrant and travelling
      populations: it is time to extend guidelines for the screening of infectious
      diseases.
AB  - The use of biological agents in the treatment of rheumatic diseases has been
      widely associated with an increased risk of reactivation of several latent
      infections. National and international guidelines recommend screening for
      infectious diseases before starting these drugs. In Western countries screening
      is limited to latent tuberculosis infection, HIV and viral hepatitis. However,
      the increasing globalisation and the remarkable number of migrating and
      travelling people worldwide make this approach no longer adequate. The Italian
      and Spanish Societies of Rheumatology and Tropical Medicine wish to issue a
      warning about the need to improve awareness of doctors about the risk of
      reactivation of infectious tropical diseases in migrant or travelling patients
      who undergo biological therapy. Thus, the Italian and Spanish Societies are now
      planning to issue specific recommendations, based on a multidisciplinary
      contribution and a systematic review of the literature, for screening and follow
      up of active and latent chronic infections in candidate patients for biological
      agents, taking into account the patient's area of origin and risk of infectious
      diseases. 

PMID- 24335920
TI  - Epiregulin gene expression as a biomarker of benefit from cetuximab in the
      treatment of advanced colorectal cancer.
AB  - BACKGROUND: Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K
      ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor
      receptor ligand epiregulin (EREG) gene expression may further predict cetuximab
      benefit. METHODS: Tumour samples from a phase III clinical trial of cetuximab
      plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA
      gene expression. Predictive effects of high vs low EREG on OS and progression
      free survival (PFS) were examined for treatment-biomarker interaction. RESULTS:
      Both EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC)
      tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')
      positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR)
      0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for
      cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12)
      and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment
      interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR
      0.49; P=0.001) in the co-biomarker-positive group. CONCLUSION: In pre-treated K
      ras wild-type status colorectal cancer, patients with high EREG gene expression
      appear to benefit more from cetuximab therapy compared with low expression.
      Epiregulin as a selective biomarker requires further evaluation.

PMID- 24335921
TI  - Cigarette smoking, alcohol intake, and risk of glioma in the NIH-AARP Diet and
      Health Study.
AB  - BACKGROUND: Although cigarette smoking and alcohol drinking increase the risk of
      several cancers and certain components of cigarette smoke and alcohol can
      penetrate the blood-brain barrier, it remains unclear whether these exposures
      influence the risk of glioma. METHODS: We examined the associations between
      cigarette smoking, alcohol intake, and risk of glioma in the National Institutes
      of Health-AARP Diet and Health Study, a prospective study of 477,095 US men and
      women ages 50-71 years at baseline. Hazard ratios (HRs) and 95% confidence
      intervals (CIs) were calculated using models with age as the time metric and
      adjusted for sex, race/ethnicity, education, and marital status. RESULTS: During
      a median 10.5 person-years of follow-up, 492 men and 212 women were diagnosed
      with first primary glioma. Among men, current, heavier smoking was associated
      with a reduced risk of glioma compared with never smoking, but this was based on
      only nine cases. No associations were observed between smoking behaviours and
      glioma risk in women. Greater alcohol consumption was associated with a decreased
      risk of glioma, particularly among men (>2 drinks per day vs <1 drink per week:
      HR=0.67, 95% CI=0.51-0.90). CONCLUSION: Smoking and alcohol drinking do not
      appear to increase the risk of glioma.

PMID- 24335922
TI  - Key differences identified between actinic keratosis and cutaneous squamous cell
      carcinoma by transcriptome profiling.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common
      malignancies in fair-skinned populations worldwide and its incidence is
      increasing. Despite previous observations of multiple genetic abnormalities in
      cSCC, the oncogenic process remains elusive. The purpose of this study was to
      elucidate key molecular events associated with progression from premalignant
      actinic keratoses (AKs) to invasive cSCC by transcriptome profiling. METHODS: We
      combined laser capture microdissection with the Affymetrix HGU133 Plus 2.0
      microarrays to profile 30 cSCC and 10 AKs. RESULTS: We identified a core set of
      196 genes that are differentially expressed between AK and cSCC, and are enriched
      for processes including epidermal differentiation, cell migration, cell-cycle
      regulation and metabolism. Gene set enrichment analysis highlighted a key role
      for the mitogen activated protein kinase (MAPK) pathway in cSCC compared with AK.
      Furthermore, the histological subtype of the tumour was shown to influence the
      expression profile. CONCLUSION: These data indicate that the MAPK pathway may be
      pivotal to the transition from AK to cSCC, thus representing a potential target
      for cSCC prevention. In addition, transcriptome differences identified between
      cSCC subtypes have important implications for future development of targeted
      therapies for this malignancy.

PMID- 24335923
TI  - Interventions to improve exercise behaviour in sedentary people living with and
      beyond cancer: a systematic review.
AB  - BACKGROUND: To systematically review the effects of interventions to improve
      exercise behaviour in sedentary people living with and beyond cancer. METHODS:
      Only randomised controlled trials (RCTs) that compared an exercise intervention
      to a usual care comparison in sedentary people with a homogeneous primary cancer
      diagnosis, over the age of 18 years were eligible. The following electronic
      databases were searched: Cochrane Central Register of Controlled Trials MEDLINE;
      EMBASE; AMED; CINAHL; PsycINFO; SportDiscus; PEDro from inception to August 2012.
      RESULTS: Fourteen trials were included in this review, involving a total of 648
      participants. Just six trials incorporated prescriptions that would meet current
      recommendations for aerobic exercise. However, none of the trials included in
      this review reported intervention adherence of 75% or more for a set prescription
      that would meet current aerobic exercise guidelines. Despite uncertainty around
      adherence in many of the included trials, the interventions caused improvements
      in aerobic exercise tolerance at 8-12 weeks (SMD=0.73, 95% CI=0.51-0.95) in
      intervention participants compared with controls. At 6 months, aerobic exercise
      tolerance is also improved (SMD=0.70, 95% CI=0.45-0.94), although four of the
      five trials had a high risk of bias; hence, caution is warranted in its
      interpretation. CONCLUSION: Expecting the majority of sedentary survivors to
      achieve the current exercise guidelines is likely to be unrealistic. As with all
      well-designed exercise programmes, prescriptions should be designed around
      individual capabilities and frequency, duration and intensity or sets,
      repetitions, intensity of resistance training should be generated on this basis.

PMID- 24335924
TI  - Prognostic model for survival of local recurrent nasopharyngeal carcinoma with
      intensity-modulated radiotherapy.
AB  - BACKGROUND: Intensity-modulated radiotherapy (IMRT) is the main salvage treatment
      for advanced locally recurrent nasopharyngeal carcinoma (NPC); however, survival
      outcomes vary. We aimed to construct a prognostic-score model to identify
      patients who could benefit from salvage IMRT. METHODS: This retrospective study
      involved 251 patients with locally recurrent NPC. The following parameters were
      analysed following IMRT: patient performance status, age, gender, late
      complications, T-stage of recurrence, synchronous nodal recurrence, primary gross
      tumour volume (GTV-nx), disease-free interval, re-irradiation dose and
      chemotherapy. The model was based on the hazard ratio coefficients of six
      significantly negative prognostic factors for survival. RESULTS: Significantly
      negative prognostic factors included Karnofsky Performance Status <=70, age >50
      years, late complications, recurrent T(3-4) stage, synchronous nodal recurrence
      and GTV-nx >30 cm(3). Three subgroups were defined according to model scores: low
      risk (0-4), intermediate risk (5-8) and high risk (9-15). The 5-year overall
      survival rates were 64.3%, 32.2% and 7.7%, respectively. The main cause of death
      was radiation-induced complications. CONCLUSION: The prognostic-score model
      demonstrated that re-irradiation with IMRT is suitable for low-risk and
      intermediate-risk patients but may be unsuitable for high-risk patients. Further
      research into the protection of critical adjacent organs to reduce late
      complications in these patients is warranted.

PMID- 24335925
TI  - Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast
      cancer cells through paracrine TGF-beta signalling.
AB  - BACKGROUND: Cancer-associated fibroblasts (CAFs) activated by tumour cells are
      the predominant type of stromal cells in breast cancer tissue. The reciprocal
      effect of CAFs on breast cancer cells and the underlying molecular mechanisms are
      not fully characterised. METHODS: Stromal fibroblasts were isolated from invasive
      breast cancer tissues and the conditioned medium of cultured CAFs (CAF-CM) was
      collected to culture the breast cancer cell lines MCF-7, T47D and MDA-MB-231.
      Neutralising antibody and small-molecule inhibitor were used to block the
      transforming growth factor-beta (TGF-beta) signalling derived from CAF-CM, which
      effect on breast cancer cells. RESULTS: The stromal fibroblasts isolated from
      breast cancer tissues showed CAF characteristics with high expression levels of
      alpha-smooth muscle actin and SDF1/CXCL12. The CAF-CM transformed breast cancer
      cell lines into more aggressive phenotypes, including enhanced cell-extracellular
      matrix adhesion, migration and invasion, and promoted epithelial-mesenchymal
      transition (EMT). Cancer-associated fibroblasts secreted more TGF-beta1 than TGF
      beta2 and TGF-beta3, and activated the TGF-beta/Smad signalling pathway in breast
      cancer cells. The EMT phenotype of breast cancer cells induced by CAF-CM was
      reversed by blocking TGF-beta1 signalling. CONCLUSION: Cancer-associated
      fibroblasts promoted aggressive phenotypes of breast cancer cells through EMT
      induced by paracrine TGF-beta1. This might be a common mechanism for acquiring
      metastatic potential in breast cancer cells with different biological
      characteristics.

PMID- 24335926
TI  - Monitoring response to cytostatic cisplatin in a HER2(+) ovary cancer model by
      MRI and in vitro and in vivo MR spectroscopy.
AB  - BACKGROUND: Limited knowledge is available on alterations induced by cytostatic
      drugs on magnetic resonance spectroscopy (MRS) and imaging (MRI) parameters of
      human cancers, in absence of apoptosis or cytotoxicity. We here investigated the
      effects of a cytostatic cisplatin (CDDP) treatment on (1)H MRS and MRI of HER2
      overexpressing epithelial ovarian cancer (EOC) cells and in vivo xenografts.
      METHODS: High-resolution MRS analyses were performed on in vivo passaged SKOV3.ip
      cells and cell/tissue extracts (16.4 or 9.4 T). In vivo MRI/MRS quantitative
      analyses (4.7 T) were conducted on xenografts obtained by subcutaneous
      implantation of SKOV3.ip cells in SCID mice. The apparent diffusion coefficient
      (ADC) and metabolite levels were measured. RESULTS: CDDP-induced cytostatic
      effects were associated with a metabolic shift of cancer cells towards
      accumulation of MRS-detected neutral lipids, whereas the total choline profile
      failed to be perturbed in both cultured cells and xenografts. In vivo MRI
      examinations showed delayed tumour growth in the CDDP-treated group, associated
      with early reduction of the ADC mean value. CONCLUSION: This study provides an
      integrated set of information on cancer metabolism and physiology for monitoring
      the response of an EOC model to a cytostatic chemotherapy, as a basis for
      improving the interpretation of non-invasive MR examinations of EOC patients.

PMID- 24335927
TI  - A quantitative approach to measure women's sexual function using
      electromyography: a preliminary study of the Kegel exercise.
AB  - BACKGROUND: Currently, the reference standard used to clinically assess sexual
      function among women is a qualitative questionnaire. Hence, a generalised and
      quantitative measurement tool needs to be available as an alternative. This study
      investigated whether an electromyography (EMG) measurement technique could be
      used to help quantify women's sexual function. MATERIAL AND METHODS: A
      preliminary intervention study was conducted on 12 female subjects, who were
      randomised into a control (n=6) and an intervention (n=6) group. Intervention
      involved a set regimen of pelvic floor muscle exercises (Kegel) and the control
      group did not have any treatment. All subjects were asked to answer a validated,
      self-rated Pelvic Organ Prolapse/Urinary Incontinence Sexual Function
      Questionnaire (PISQ). EMG measurements of the pelvic floor muscles (PFM) and the
      abdominal muscles were taken from all women at recruitment and 8 weeks after
      study commencement. RESULTS: After 8 weeks, most of the subjects in the control
      group did not display any noted positive difference in either PISQ score (4/6) or
      in their muscle strength (4/6). However, a noted progressive difference were
      observed in subjects who were placed in the Kegel group; PISQ score (5/6) and
      muscles strength (4/6). CONCLUSIONS: The noted difference in the Kegel group
      subjects was that if progress is observed in the sexual function, improvement is
      also observed in the strength of at least 2 types of muscles (either abdominal or
      PFM muscles). Thus, EMG measurement is a potential technique to quantify the
      changes in female sexual function. Further work will be conducted to validate
      this assumption.

PMID- 24335929
TI  - Metabolomic and network analysis of pharmacotherapies for sensorineural hearing
      loss.
AB  - HYPOTHESIS: Different pharmacotherapies for sensorineural hearing loss (SNHL) are
      interconnected in metabolic networks with molecular hubs. BACKGROUND:
      Sensorineural hearing loss is the most common sensory deficit worldwide. Dozens
      of drugs have shown efficacy against SNHL in animal studies and a few in human
      studies. Analyzing metabolic networks that interconnect these drugs will point to
      and prioritize development of new pharmacotherapies for human SNHL. METHODS:
      Drugs that have shown efficacy in treating mammalian SNHL were identified through
      PubMed literature searches. The drugs were analyzed using the metabolomic
      analysis and the "grow-tool function" in ingenuity pathway analysis (IPA). The
      top 3 most interconnected molecules and drugs (i.e., the hubs) within the
      generated networks were considered important targets for the treatment of SNHL.
      RESULTS: A total of 70 drugs were investigated with IPA. The metabolomic analysis
      revealed 2 statistically significant networks (Networks 1 and 2). A network
      analysis using the "grow-tool function" generated one statistically significant
      network (Network 3). Hubs of these networks were as follows: P38 mitogen
      activated protein kinases (P38 MAPK), p42/p44 MAP kinase (ERK1/2) and glutathione
      for Network 1; protein kinase B (Akt), nuclear factor kappa B (NFkB) and ERK for
      Network 2; and dexamethasone, tretinoin, and cyclosporin A for Network 3.
      CONCLUSION: Metabolomic and network analysis of the existing pharmacotherapies
      for SNHL has pointed to and prioritized a number of potential novel targets for
      treatment of SNHL.

PMID- 24335928
TI  - Efficient keratinocyte differentiation strictly depends on JNK-induced soluble
      factors in fibroblasts.
AB  - Previous studies demonstrated that fibroblast-derived and JUN-dependent soluble
      factors have a crucial role on keratinocyte proliferation and differentiation
      during cutaneous wound healing. Furthermore, mice with a deficiency in Jun N
      terminal kinases (JNKs) , JNK1 or JNK2, showed impaired skin development and
      delayed wound closure. To decipher the role of dermal JNK in keratinocyte
      behavior during these processes, we used a heterologous coculture model combining
      primary human keratinocytes and murine fibroblasts. Although cocultured JNK1/JNK2
      deficient fibroblasts did not affect keratinocyte proliferation, temporal
      monitoring of the transcriptome of differentiating keratinocytes revealed that
      efficient keratinocyte differentiation not only requires the support by
      fibroblast-derived soluble factors, but is also critically dependent on JNK1 and
      JNK2 signaling in these cells. Moreover, we showed that the repertoire of
      fibroblast transcripts encoding secreted proteins is severely disarranged upon
      loss of JNK under the coculture conditions applied. Finally, our data demonstrate
      that efficient keratinocyte terminal differentiation requires constant presence
      of JNK-dependent and fibroblast-derived soluble factors. Taken together, our
      results imply that mesenchymal JNK has a pivotal role in the paracrine cross talk
      between dermal fibroblasts and epidermal keratinocytes during wound healing. 

PMID- 24335930
TI  - Auditory cortical maturation in children with sequential bilateral cochlear
      implants.
AB  - OBJECTIVE: To assess the effect of sequential bilateral cochlear implantation on
      auditory, cortical maturation after various periods of unilateral cochlear
      implant use. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic
      referral center. PATIENTS: Thirty prelingually deaf children, who received their
      first implant at a mean age of 1.8 years and their second implant at a mean age
      of 5.3 years. INTERVENTION: Sequential bilateral cochlear implantation. MAIN
      OUTCOMES MEASURE: The electrically evoked auditory cortical response (EACR) was
      evoked by the 2 implants separately after 12 and 24 months of bilateral cochlear
      implant use. P1 and N2 latencies and RMS amplitudes were compared between both
      implant sides and were compared with those of a group of 27 age-matched children
      with normal hearing. RESULTS: EACR latencies diminished over time for both
      implant sides. RMS amplitudes and P1 latencies elicited by the second implant
      were still significantly different from that of the first implant after 24 month.
      After 24 months, the difference in N2 latencies between both implant sides was no
      longer significant, although still apparent. Interimplant delay had an adverse
      effect on RMS amplitudes and waveform morphology. EACR latencies were age
      appropriate, although RMS amplitudes evoked by the second implant were smaller
      than those of the children with normal hearing. CONCLUSION: Auditory cortical
      maturation is possible after extended unilateral cochlear implant use, although
      responses evoked by the second implant still lack behind that of the experienced
      first implant. It is not clear if the auditory cortical response will become
      similar on both implant sides over time, especially for the children with longer
      interimplant delays.

PMID- 24335931
TI  - Ipsilateral cochlear implantation after cochlear nerve preserving vestibular
      schwannoma surgery in patients with neurofibromatosis type 2.
AB  - OBJECTIVE: To investigate the outcomes from ipsilateral simultaneous or
      sequential cochlear implantation in patients with neurofibromatosis type 2 (NF2)
      after vestibular schwannoma removal with cochlear nerve preservation. STUDY
      DESIGN: Retrospective case series. SETTING: Single tertiary referral NF2 center.
      PATIENTS: Six patients with NF2. INTERVENTION: Removal of vestibular schwannoma
      (VS) with preservation of the cochlear nerve and cochlear implantation. Four
      patients had their surgery via a translabyrinthine approach. Two patients had a
      retrosigmoid approach. A cochlear implant was inserted at the same time as tumor
      removal in 4 cases and sequentially in 2 cases. MAIN OUTCOME MEASURES: Surgical
      and audiometric outcomes using Bamford-Kowal-Bench (BKB) and City of New York
      University (CUNY) sentence scores. RESULTS: The average age at implantation was
      24 years (range, 15-36 yr). Follow-up ranged from 5 to 93 months, with an average
      of 38 months. All patients had useful hearing in the contralateral ear before
      surgery. One patient gained no benefit from cochlear implantation and proceeded
      to have an auditory brainstem implant. Of those that had functional cochlear
      nerves, the average BKB score in quiet was 64%, BKB score in noise was 42%, and
      CUNY score with lipreading was 97%. Results varied within the group, but all
      patients gained significant benefit and continue to use their CI at least
      intermittantly. CONCLUSION: The present series demonstrates that in selected
      cases, cochlear implantation can be successful after a translabyrinthine approach
      for VS removal and for restoring hearing after failed retrosigmoid hearing
      preservation surgery. All patients found the cochlear implant offered useful
      hearing even in the presence of contralateral hearing.

PMID- 24335932
TI  - Insertion depth angles of cochlear implant arrays with varying length: a temporal
      bone study.
AB  - HYPOTHESIS: The aim of the study is to investigate the insertion depth angles for
      different types of electrode arrays and its variability depending on the
      individual cochlear size. BACKGROUND: Preoperative estimation of the insertion
      depth angles for different electrode arrays can help surgeons choose the optimal
      electrode length, especially for low-frequency residual hearing preservation.
      METHODS: Four different electrode arrays varying in lengths (20, 24, 28, and 31
      mm) were inserted in 10 temporal bones to quantify the insertion depth angle of
      each inserted electrode. High-resolution 3D radiographs provided by Flat Panel
      Computed Volume Tomography (FPCT) were used to determine electrode array
      insertion depth angle and diameter of the cochlea's basal turn. RESULTS: The high
      resolution FPCT images from all electrode arrays inserted into the temporal bones
      allowed reliable measurements of insertion depth angles. In particular,
      statistically significant different insertion depth angles between the various
      array types were identified. The insertion of the 20-, 24-, 28-, and 31-mm arrays
      yielded a mean insertion depth angle of 341 degrees (SD, 22 degrees), 477 degrees
      (SD, 36 degrees), 587 degrees (SD, 42 degrees), and 673 degrees (SD, 38 degrees),
      respectively. Furthermore, a statistically significant negative correlation
      between insertion depth angle and diameter of the cochlea's basal turn was found
      for the 20- and 31-mm arrays. CONCLUSION: The results suggest an individually
      adapted length of electrode arrays, which should be taken into account for an
      improved decision paradigm for patients scheduled for cochlear implantation. This
      is of particular importance for patients with low-frequency residual hearing.

PMID- 24335933
TI  - Longitudinal follow-up after pediatric myringoplasty: long-term outcome is
      defined at 12 months.
AB  - OBJECTIVES: To determine the true success rate of pediatric myringoplasty.
      MATERIALS AND METHODS: This retrospective study analyzed 67 pediatric
      myringoplasties performed at Hyogo College of Medicine between 2000 and 2009. We
      divided the pediatric population into a younger group (<10 yr old, n = 41) and an
      older group (>=10 yr old, n = 26). We also compared the pediatric group (n = 67)
      with a group of adult patients (n = 63) who underwent myringoplasty between 2008
      and 2009. RESULTS: In the pediatric group, graft success was achieved in 81% of
      the cases. The pathologic success rate, which was based on the presence of an
      intact membrane without adhesion, retraction, or effusion, was 73%. Furthermore,
      an intact membrane with successful hearing was achieved in 67% of the cases at 12
      month follow-up. The graft success rate of the adult group was 90%, and there was
      no significant difference with the pediatric group. However, when success was
      defined as pathologic success or pathologic success with hearing improvement,
      there were significant differences in success rates between pediatric and adults
      groups (p < 0.05). The success rate of pathologic success with hearing
      improvement was significantly lower in children with abnormal contralateral ears
      or poor contralateral air cell development than in children with healthy
      contralateral ears (p < 0.01) or good contralateral air cell development (p <
      0.05). CONCLUSION: These findings suggest that the success of pediatric
      myringoplasty should be defined as an intact tympanic membrane without evidence
      of adhesions, retraction, or effusion, together with hearing improvement at the
      12-month follow-up.

PMID- 24335934
TI  - Treatment outcomes in patients treated with CyberKnife radiosurgery for
      vestibular schwannoma.
AB  - OBJECTIVE: To evaluate tumor control, hearing, tinnitus, and balance outcomes of
      patients treated with CyberKnife (CK) radiosurgery for vestibular schwannoma
      (VS). STUDY DESIGN: Retrospective series review. SETTING: Tertiary referral
      center. PATIENTS: All patients treated with CK radiosurgery for vestibular
      schwannoma by a multidisciplinary radiosurgical team from August 2005 to November
      2011. The median age was 59 years, and mean follow-up was 40 months. Seventy
      three patients were treated (63 primary radiosurgery and 10 postsurgical).
      INTERVENTIONS: CK radiosurgery, serial MRI imaging, comprehensive audiometry,
      Tinnitus Handicap Inventory (THI) scores, and Activities-Specific Balance
      Confidence Scale (ABC). MAIN OUTCOME MEASURES: Tumor control defined as 2 mm
      linear growth or lower or less than 20% increase in tumor volume (TV), measured
      in cubic centimeter, after a minimum of 12 months of monitoring, audiogram
      profiles, THI, and ABC surveys. RESULTS: Of those treated with CK as primary
      modality, 83% had 0- to 2-mm growth (tumor control or stable) and 17% grew
      greater than 2 mm. Of the tumors that were stable, 29% shrank 2 mm or greater.
      Volumetric analysis found that 74% of tumors had less than 20% TV growth, whereas
      26% exhibited 20% or greater increase in TV. Of those deemed stable, 65% shrank
      20% or greater TV; 95% of patients did not need additional surgical intervention,
      3 required salvage surgery and 1 underwent additional radiosurgery. The majority
      of patients started with Class D hearing, but of those with Class A or B hearing
      before treatment, 53.5% maintained serviceable hearing at 3 years of follow-up.
      The pretreatment and posttreatment median THI Grades were both 1. The
      pretreatment and posttreatment ABC scores were unchanged at 81%. CONCLUSION: The
      LINAC-based CK (18 Gy over 3 fractions at 80% isodose line) provides tumor
      control rates comparable to other forms of radiosurgery. Analysis for tumor
      growth was positive for 17% using maximum linear diameters and 26% with a
      volumetric workstation. This discrepancy is consistent with previous reports
      where volumetric models were found to be more sensitive in establishing growth.
      Serviceable hearing was comparable to previous SRS and SRT reports with an
      overall hearing preservation of 53.5%. This number was 77% in those with pre
      Class A hearing. SRS did not affect pretreatment tinnitus or vestibular function.

PMID- 24335935
TI  - Vestibular schwannoma microsurgery for recurrent tumors after radiation therapy
      or previous surgical resection.
AB  - OBJECTIVE: The purpose of this study is to compare the outcomes in patients who
      underwent microsurgical resection for recurrent vestibular schwannoma after
      microsurgical resection and previous radiation therapy. STUDY DESIGN:
      Retrospective study. SETTING: University hospital. PATIENTS: Fifteen patients,
      who underwent microsurgical resection for recurrent vestibular schwannoma after
      previous surgery (group A), and 5 patients, who underwent microsurgical resection
      after previous radiation therapy (group B) were included. INTERVENTION: Surgical
      resection after radiation therapy or previous surgical resection. MAIN OUTCOME
      MEASURES: Intraoperative findings and postoperative facial nerve function were
      investigated in groups A and B. RESULTS: Mean tumor volumes were 18.4 +/- 2.44
      cm3 in group A and 19.0 +/- 1.53 cm3 in group B. Total resection was achieved in
      10 patients (67%) of group A and in 3 patients (60.0%) of group B. The tumor was
      more difficult to resect because of severe adhesions to the facial nerve.
      Anatomic facial nerve preservation could be achieved in 19 patients. Mean follow
      up time was 80 months for group A and 28 months for group B. At last follow-up, 7
      patients (53.8%) of group A had a good facial nerve function. In 3 patients
      (75.0%) of group B, the preoperative facial nerve function was preserved
      postoperatively. Preexistent facial paresis, large tumor with extrameatal growth
      and brainstem compression correlated with poor postoperative facial nerve
      function. CONCLUSION: Surgical outcome of recurrent vestibular schwannoma is more
      unsatisfactory than after primary surgery. It remains to be clarified whether
      previous surgery may implicate a higher risk for postoperative facial nerve
      function than previous radiation therapy upon surgery for tumor recurrence.

PMID- 24335936
TI  - Comments on 'Anti-IgE therapy for eosinophilic disorders'.

PMID- 24335937
TI  - Unbiased stereologic estimation of the spatial distribution of Paget's disease in
      the human temporal bone.
AB  - BACKGROUND: It has been suggested that Paget's disease of bone and otosclerosis
      may share a myxoviral etiology. However, the association between virus infection
      and pathologic bone remodeling is still controversial. The aim of this study was
      to estimate the spatial distribution of pagetic bone remodeling around the inner
      ear space and to compare it with that of otosclerosis in a contemporary context
      of temporal bone dynamics. MATERIALS AND METHODS: From the temporal bone
      collection of Massachusetts Eye and Ear Infirmary, 15 of 29 temporal bones with
      Paget's disease were selected to obtain an independent sample. All volume
      distributions were obtained along the normal axis of capsular bone remodeling
      activity by the use of vector-based stereology. RESULTS: Pagetic bone remodeling
      was distributed centrifugally around the inner ear space at the individual and
      the general level. This pattern is similar to the normal distribution of
      perilabyrinthine bone remodeling but entirely different from the spatial location
      of otosclerosis, which are focal and centripetally distributed around the inner
      ear space. CONCLUSION: In Paget's disease, the antiresorptive barrier around the
      inner ear space becomes gradually overruled as pagetic bone resorption invades
      the otic capsule from the outside. However, in otosclerosis, this barrier has
      somehow failed locally inside the otic capsule. Although virus infections
      potentially may trigger osteoclastic activity additional pathogenetic factors are
      needed to explain the organ-specific nature and spatial properties of
      otosclerosis.

PMID- 24335938
TI  - Natural history of vestibular schwannoma growth and hearing decline in newly
      diagnosed neurofibromatosis type 2 patients.
AB  - OBJECTIVE: To determine the rate of growth in vestibular schwannomas and the rate
      of hearing decline in neurofibromatosis type 2 (NF2) patients not undergoing
      active treatment STUDY DESIGN: Prospective study. SETTING: Data were collected at
      10 NF2 centers, including hospital-based, academic, and tertiary care centers.
      PATIENTS: 120 NF2 patients with 200 vestibular schwannomas. OUTCOME MEASURES:
      Hearing decline, defined as a decrease in word recognition score outside the 95%
      critical difference compared with baseline, and radiographic progression, defined
      as a 20% or greater increase in tumor volume compared with baseline. RESULTS:
      During a total of 313.4 patient-years of follow-up, the rate of hearing decline
      was 5% at 1 year, 13% at 2 years, and 16% at 3 years; the rate of tumor
      progression was 31% at 1 year, 64% at 2 years, and 79% at 3 years. For this
      cohort, the median time to tumor progression (14 mo) was significantly shorter
      than the median time to hearing decline (62.0 mo). CONCLUSION: These data provide
      potentially useful information for the design of clinical trials for NF2
      vestibular schwannoma.

PMID- 24335939
TI  - A case of generalized varicelliform eruption after herpes zoster oticus.
AB  - OBJECTIVE: To report the case of a healthy man with a previously unreported
      combination of generalized varicelliform eruption and herpes zoster oticus.
      PATIENT: A 44-year-old immunocompetent man who developed generalized
      varicelliform eruption after peripheral facial palsy with herpes zoster oticus
      without any underlying immunocompromised state. MAIN OUTCOME MEASURE: The skin
      lesion was improved during his hospitalization period. Facial palsy was
      completely cured after 2 months of treatment. CONCLUSION: Herpes zoster oticus
      occurs rarely and accounts for approximately 1% of all cases of herpes zoster and
      generalized varicelliform eruption occurs in 2% to 10% of unselected patients
      with herpes zoster. Most of these patients have an underlying condition that is
      associated with an immunocompromised state such as lymphoproliferative disease.
      Varicelliform eruptions are extremely rare among healthy patients without any
      underlying disease.

PMID- 24335940
TI  - Evaluation of auditory cortical development in the early stages of post cochlear
      implantation using mismatch negativity measurement.
AB  - OBJECTIVE: The aim of this study was to investigate auditory cortical development
      using mismatch negativity (MMN) in prelingual severe-to-profound hearing-impaired
      children from the stage of cochlear implant (CI) power-up to 6 months after power
      up. METHOD: Eighteen children were recruited and examined at the stage of CI
      initial power-up (M0), as well as several follow-up periods, that is, 1 month
      (M1), 3 months (M3), and 6 months (M6) after CI power-up. The MMN responses were
      measured using a 128-Channel Dense Array EEG System. The group average and
      individual MMN analysis were used to investigate the longitudinal changes of the
      MMN characteristics. The relationship between MMN characteristics and scores of
      categories of auditory performance (CAP) was also investigated. RESULTS: Although
      the MMN incidence was much lower at the periods of M0 and M1, significantly
      higher MMN incidence was found in M3 and M6. The MMN latencies decreased
      significantly from M3 to M6, but no significant difference in the amplitudes was
      found between these periods. There was a negative correlation between the
      increment of CAP scores and decrement of MMN latency from M3 to M6. CONCLUSION:
      MMN incidence increment and latency decrement are likely to be the objective and
      noninvasive indicators for evaluating auditory central development at an early
      stage in children after cochlear implantation. Moreover, the latency decrement
      from M3 to M6 correlated significantly with the increment of the CAP scores,
      indicating a fast maturation period, which might be a key period for auditory
      rehabilitation.

PMID- 24335955
TI  - Comparison of the cerebrospinal fluid (CSF) toluidine red unheated serum test and
      the CSF rapid plasma reagin test with the CSF venereal disease research
      laboratory test for diagnosis of neurosyphilis among HIV-negative syphilis
      patients in China.
AB  - In this study, we aimed to investigate the performance of nontreponemal antibody
      tests in cerebrospinal fluid (CSF) specimens from syphilis patients. From
      September 2009 to September 2012, CSF specimens were collected at the Shanghai
      Skin Disease Hospital in Shanghai, China, from 1,132 syphilis patients without
      HIV infection, including 154 with symptomatic and 56 with asymptomatic
      neurosyphilis. All of the CSF specimens underwent testing with a rapid plasma
      reagin (RPR) test, an RPR-V (commercial RPR antigen diluted 1:2 in 10% saline)
      test, the toluidine red unheated serum test (TRUST), and the Venereal Disease
      Research Laboratory (VDRL) test. Specificities, sensitivities, positive
      predictive values (PPVs), negative predictive values (NPVs), and kappa values
      were calculated to determine the performances of the tests. We compared results
      of the CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST among patients with
      symptomatic and asymptomatic neurosyphilis who had reactive CSF-Treponema
      pallidum particle agglutination (TPPA) test results. Overall, the CSF-VDRL test
      was reactive in 261 patients (23.1%). There were no cases in which the CSF-VDRL
      was nonreactive and CSF-RPR, CSF-RPR-V, or CSF-TRUST was reactive. Agreement
      between the results of CSF-TRUST and CSF-RPR was almost perfect (kappa=0.861),
      with substantial agreement between the results of CSF-RPR and CSF-RPR-V
      (kappa=0.740). The sensitivities of CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST
      were 81.4%, 76.2%, 79.5%, and 76.2%, respectively. Compared to CSF-VDRL, CSF-RPR,
      CSF-RPR-V, and CSF-TRUST had comparable PPVs and NPVs. However, the specificity
      of CSF-VDRL (90.3%) was significantly lower than those of the other tests (92.7
      to 93.4%). Therefore, CSF-RPR, CSF-RPR-V, and CSF-TRUST can be considered
      alternative tests for neurosyphilis diagnosis in HIV-negative populations,
      particularly when the CSF-VDRL is not available.

PMID- 24335956
TI  - Pork meat as a potential source of Salmonella enterica subsp. arizonae infection
      in humans.
AB  - Salmonella enterica subsp. arizonae was isolated from 13 of 123 slaughtered pigs
      in central Greece. The samples cultured were feces, ileum tissue, mesenteric
      lymph nodes, and gallbladder swabs. A total of 74 isolates from 492 samples were
      identified as Salmonella spp. by use of standard laboratory culture media and two
      commercial micromethods and by use of a polyvalent slide agglutination test for
      the detection of O and H antigens. Among them were 19 (25.68%) suspected to be S.
      enterica subsp. arizonae according to analysis with standard laboratory culture
      media. Of those, 14 were identified as S. enterica subsp. arizonae by the API 20E
      (bioMerieux, France) and the Microgen GnA+B-ID (Microgen Bioproducts, Ltd.,
      United Kingdom) identification systems. All the isolates were tested for
      resistance to 23 antimicrobials. Strains identified as S. enterica subsp.
      arizonae were resistant to 17 (70.8%) antibiotics. The highest proportions of
      resistance were observed for sulfamethoxazole-trimethoprim (71.4%), tetracycline
      (71.4%), ampicillin (64.3%), and amoxicillin (57.1%). Two isolates were resistant
      to aztreonam (7.1%) and tigecycline (7.1%), used only for the treatment of
      humans. Thus, pork meat may play a role in the transmission of antibiotic
      resistant S. enterica subsp. arizonae to human consumers. This is the first
      report of S. enterica subsp. arizonae isolation from pigs. 

PMID- 24335957
TI  - A phenylalanine rotameric switch for signal-state control in bacterial
      chemoreceptors.
AB  - Bacterial chemoreceptors are widely used as a model system for elucidating the
      molecular mechanisms of transmembrane signalling and have provided a detailed
      understanding of how ligand binding by the receptor modulates the activity of its
      associated kinase CheA. However, the mechanisms by which conformational signals
      move between signalling elements within a receptor dimer and how they control
      kinase activity remain unknown. Here, using long molecular dynamics simulations,
      we show that the kinase-activating cytoplasmic tip of the chemoreceptor
      fluctuates between two stable conformations in a signal-dependent manner. A
      highly conserved residue, Phe396, appears to serve as the conformational switch,
      because flipping of the stacked aromatic rings of an interacting F396-F396' pair
      in the receptor homodimer takes place concomitantly with the signal-related
      conformational changes. We suggest that interacting aromatic residues, which are
      common stabilizers of protein tertiary structure, might serve as rotameric
      molecular switches in other biological processes as well. 

PMID- 24335958
TI  - Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and
      translation.
AB  - The epithelial-mesenchymal transition (EMT) enhances cellular invasiveness and
      confers tumor cells with cancer stem cell-like characteristics, through
      transcriptional and translational mechanisms. The mechanisms maintaining
      transcriptional and translational repression of EMT and cellular invasion are
      poorly understood. Herein, the cell fate determination factor Dachshund (DACH1),
      suppressed EMT via repression of cytoplasmic translational induction of Snail by
      inactivating the Y box-binding protein (YB-1). In the nucleus, DACH1 antagonized
      YB-1-mediated oncogenic transcriptional modules governing cell invasion. DACH1
      blocked YB-1-induced mammary tumor growth and EMT in mice. In basal-like breast
      cancer, the reduced expression of DACH1 and increased YB-1 correlated with poor
      metastasis-free survival. The loss of DACH1 suppression of both cytoplasmic
      translational and nuclear transcriptional events governing EMT and tumor invasion
      may contribute to poor prognosis in basal-like forms of breast cancer, a
      relatively aggressive disease subtype.

PMID- 24335959
TI  - miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell
      carcinoma invasion and metastasis.
AB  - MicroRNAs offer tools to identify and treat invasive cancers. Using highly
      invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in
      vitro and in vivo selection protocols from poorly invasive parental cell
      populations, we used microarray expression analysis to identify a relative and
      specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p
      correlated with poor overall survival of patients with OSCCs. miR-491-5p
      overexpression in invasive OSCC cells suppressed their migratory behavior in
      vitro and lung metastatic behavior in vivo. We defined the G-protein-coupled
      receptor kinase-interacting protein 1 (GIT1)-as a direct target gene for miR-491
      5p control. GIT1 overexpression was sufficient to rescue miR-491-5p-mediated
      inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing
      phenocopied the ability of miR-491-5p to inhibit migration/invasion and
      metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p
      overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent
      decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK,
      EGF/EGFR-mediated extracellular signal-regulated kinase (ERK1/2) activation, and
      MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were
      elevated relative to paired normal tissues and were correlated with lymph node
      metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in
      OSCCs, where they informed tumor grade. Together, our findings identify a
      functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers
      for prognosis in this cancer.

PMID- 24335960
TI  - Histone chaperone CHAF1A inhibits differentiation and promotes aggressive
      neuroblastoma.
AB  - Neuroblastoma arises from the embryonal neural crest secondary to a block in
      differentiation. Long-term patient survival correlates inversely with the extent
      of differentiation, and treatment with retinoic acid or other prodifferentiation
      agents improves survival modestly. In this study, we show the histone chaperone
      and epigenetic regulator CHAF1A functions in maintaining the highly
      dedifferentiated state of this aggressive malignancy. CHAF1A is a subunit of the
      chromatin modifier chromatin assembly factor 1 and it regulates H3K9
      trimethylation of key target genes regulating proliferation, survival, and
      differentiation. Elevated CHAF1A expression strongly correlated with poor
      prognosis. Conversely, CHAF1A loss-of-function was sufficient to drive neuronal
      differentiation in vitro and in vivo. Transcriptome analysis of cells lacking
      CHAF1A revealed repression of oncogenic signaling pathways and a normalization of
      glycolytic metabolism. Our findings demonstrate that CHAF1A restricts neural
      crest differentiation and contributes to the pathogenesis of high-risk
      neuroblastoma.

PMID- 24335961
TI  - The CXCL7/CXCR1/2 axis is a key driver in the growth of clear cell renal cell
      carcinoma.
AB  - Mutations in the von Hippel-Lindau gene upregulate expression of the central
      angiogenic factor VEGF, which drives abnormal angiogenesis in clear cell renal
      cell carcinomas (ccRCC). However, the overexpression of VEGF in these tumors was
      not found to correlate with overall survival. Here, we show that the
      proangiogenic, proinflammatory cytokine CXCL7 is an independent prognostic factor
      for overall survival in this setting. CXCL7 antibodies strongly reduced the
      growth of ccRCC tumors in nude mice. Conversely, conditional overexpression of
      CXCL7 accelerated ccRCC development. CXCL7 promoted cell proliferation in vivo
      and in vitro, in which expression of CXCL7 was induced by the central
      proinflammatory cytokine interleukin (IL)-1beta. ccRCC cells normally secrete low
      amounts of CXCL7; it was more highly expressed in tumors due to high levels of IL
      1beta there. We found that a pharmacological inhibitor of the CXCL7 receptors
      CXCR1 and CXCR2 (SB225002) was sufficient to inhibit endothelial cell
      proliferation and ccRCC growth. Because CXCR1 and CXCR2 are present on both
      endothelial and ccRCC cells, their inhibition affected both the tumor vasculature
      and the proliferation of tumor cells. Our results highlight the CXCL7/CXCR1/CXCR2
      axis as a pertinent target for the treatment of ccRCC.

PMID- 24335962
TI  - Targeting Akt3 signaling in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is currently the only major breast tumor
      subtype without effective targeted therapy and, as a consequence, in general has
      a poor outcome. To identify new therapeutic targets in TNBC, we performed a short
      hairpin RNA (shRNA) screen for protein kinases commonly amplified and
      overexpressed in breast cancer. Using this approach, we identified AKT3 as a gene
      preferentially required for the growth of TNBCs. Downregulation of Akt3
      significantly inhibits the growth of TNBC lines in three-dimensional (3D)
      spheroid cultures and in mouse xenograft models, whereas loss of Akt1 or Akt2
      have more modest effects. Akt3 silencing markedly upregulates the p27 cell-cycle
      inhibitor and this is critical for the ability of Akt3 to inhibit spheroid
      growth. In contrast with Akt1, Akt3 silencing results in only a minor enhancement
      of migration and does not promote invasion. Depletion of Akt3 in TNBC sensitizes
      cells to the pan-Akt inhibitor GSK690693. These results imply that Akt3 has a
      specific function in TNBCs; thus, its therapeutic targeting may provide a new
      treatment option for this tumor subtype.

PMID- 24335963
TI  - Safety of second-generation rotavirus vaccines, intussusception.
AB  - PURPOSE OF REVIEW: This article discusses new data available on the safety of the
      second-generation rotavirus vaccines both in the United States and
      internationally. RECENT FINDINGS: Second-generation rotavirus vaccines are both
      highly effective against rotavirus disease. Recent data from passive and active
      surveillance systems in the United States indicate that RV1 and RV5 vaccines may
      possibly cause a small increase in the risk of intussusception; an estimated 1-3
      US infants out of 100 000 might develop intussusception within 7 days of getting
      their first dose of rotavirus vaccine. Parents and health providers should be
      aware of the small risk of intussusception, the signs and symptoms of
      intussusception, and the need for prompt care. SUMMARY: Taking into consideration
      available data on the benefits and risks, Centers for Disease Control and
      Prevention (CDC) continues to recommend that all US infants receive rotavirus
      vaccine based on the age and precaution/contraindication criteria. The benefits
      of RV5 and RV1 outweigh the small excess risk of intussusception. Safety
      monitoring will continue, both in the United States and internationally, to
      further quantitate the intussusception risk following each vaccine.

PMID- 24335965
TI  - Moments when utilities are functional.

PMID- 24335964
TI  - Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in
      Vivo and ex Vivo.
AB  - Despite progress in detecting circulating tumor cells (CTCs), existing assays
      still have low sensitivity (1-10 CTC/mL) due to the small volume of blood samples
      (5-10 mL). Consequently, they can miss up to 103-104 CTCs, resulting in the
      development of barely treatable metastasis. Here we analyze a new concept of in
      vivo CTC detection with enhanced sensitivity (up to 102-103 times) by the
      examination of the entire blood volume in vivo (5 L in adults). We focus on in
      vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or
      targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances,
      magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time
      spectral identification, nonlinear signal amplification, and the integration with
      PAFC in vitro. We demonstrate PAFC's capability to detect rare leukemia, squamous
      carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in
      preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well
      as the release of CTCs from primary tumors triggered by palpation, biopsy or
      surgery, increasing the risk of metastasis. CTC lifetime as a balance between
      intravasation and extravasation rates was in the range of 0.5-4 h depending on a
      CTC metastatic potential. We introduced theranostics of CTCs as an integration of
      nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC
      counting. In vivo data were verified with in vitro PAFC demonstrating a higher
      sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional
      assays. Further developments include detection of circulating cancer-associated
      microparticles, and super-rsesolution PAFC beyond the diffraction and spectral
      limits. 

PMID- 24335966
TI  - Safety assessment of ammonium hectorites as used in cosmetics.
AB  - The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 4
      ammonium hectorite compounds used in cosmetics: disteardimonium hectorite,
      dihydrogenated tallow benzylmonium hectorite, stearalkonium hectorite, and
      quaternium-18 hectorite. These ingredients function in cosmetics mainly as
      nonsurfactant suspending agents. The Panel reviewed available animal and human
      data and concluded that these ammonium hectorite compounds were safe as cosmetic
      ingredients in the practices of use and concentration as given in this safety
      assessment. 

PMID- 24335967
TI  - Safety assessment of alpha-amino acids as used in cosmetics.
AB  - The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of alpha
      amino acids, which function primarily as hair- and skin-conditioning agents in
      cosmetic products. The safety of alpha-amino acids as direct food additives has
      been well established based on extensive research through acute and chronic
      dietary exposures. The Panel focused its review on dermal irritation and
      sensitization data relevant to the use of these ingredients in topical cosmetics.
      The Panel concluded that alpha-amino acids were safe as cosmetic ingredients in
      the practices of use and concentration of this safety assessment. 

PMID- 24335968
TI  - Amended safety assessment of formaldehyde and methylene glycol as used in
      cosmetics.
AB  - Formaldehyde and methylene glycol may be used safely in cosmetics if established
      limits are not exceeded and are safe for use in nail hardeners in the present
      practices of use and concentration, which include instructions to avoid skin
      contact. In hair-smoothing products, however, in the present practices of use and
      concentration, formaldehyde and methylene glycol are unsafe. Methylene glycol is
      continuously converted to formaldehyde, and vice versa, even at equilibrium,
      which can be easily shifted by heating, drying, and other conditions to increase
      the amount of formaldehyde. This rapid, reversible formaldehyde/methylene glycol
      equilibrium is distinguished from the slow, irreversible release of formaldehyde
      resulting from the so-called formaldehyde releaser preservatives, which are not
      addressed in this safety assessment (formaldehyde releasers may continue to be
      safely used in cosmetics at the levels established in their individual Cosmetic
      Ingredient Review safety assessments). 

PMID- 24335969
TI  - Long-term effects of spironolactone in peritoneal dialysis patients.
AB  - ESRD treated with dialysis is associated with increased left ventricular
      hypertrophy, which, in turn, is related to high mortality. Mineralocorticoid
      receptor antagonists improve survival in patients with chronic heart failure;
      however, the effects in patients undergoing dialysis remain uncertain. We
      conducted a multicenter, open-label, prospective, randomized trial with 158
      patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1
      receptor antagonist and undergoing peritoneal dialysis with and without (control
      group) spironolactone for 2 years. As a primary endpoint, rate of change in left
      ventricular mass index assessed by echocardiography improved significantly at 6
      (P=0.03), 18 (P=0.004), and 24 (P=0.01) months in patients taking spironolactone
      compared with the control group. Rate of change in left ventricular ejection
      fraction improved significantly at 24 weeks with spironolactone compared with
      nontreatment (P=0.02). The benefits of spironolactone were clear in patients with
      reduced residual renal function. As secondary endpoints, renal Kt/V and dialysate
      to-plasma creatinine ratio did not differ significantly between groups during the
      observation period. No serious adverse effects, such as hyperkalemia, occurred.
      In this trial, spironolactone prevented cardiac hypertrophy and decreases in left
      ventricular ejection fraction in patients undergoing peritoneal dialysis, without
      significant adverse effects. Further studies, including those to determine
      relative effectiveness in women and men and to evaluate additional secondary
      endpoints, should confirm these data in a larger cohort.

PMID- 24335970
TI  - Claudin-14 underlies Ca++-sensing receptor-mediated Ca++ metabolism via NFAT
      microRNA-based mechanisms.
AB  - Pathologic dysregulation of extracellular calcium metabolism is difficult to
      correct. The extracellular Ca(++)-sensing receptor (CaSR), a G protein-coupled
      receptor that regulates renal Ca(++) handling through changes in paracellular
      channel permeability in the thick ascending limb, has emerged as an effective
      pharmacological candidate for managing calcium metabolism. However, manipulation
      of CaSR at the systemic level causes promiscuous effects in the parathyroid
      glands, kidneys, and other tissues, and the mechanisms by which CaSR regulates
      paracellular transport in the kidney remain unknown. Here, we describe a CaSR
      NFATc1-microRNA-claudin-14 signaling pathway in the kidney that underlies
      paracellular Ca(++) reabsorption through the tight junction. With CaSR-specific
      pharmacological reagents, we show that the in vivo gene expression of claudin-14
      is regulated through a transcriptional mechanism mediated by NFATc1-microRNA and
      associated chromatin remodeling. Transgenic knockout and overexpression
      approaches showed that claudin-14 is required for CaSR-regulated renal Ca(++)
      metabolism. Together, our results define an important signaling cascade that,
      when dysregulated, may mediate Ca(++) imbalance through changes in tight junction
      permeability. 

PMID- 24335971
TI  - Physical activity and change in estimated GFR among persons with CKD.
AB  - Physical activity may counteract metabolic disturbances that promote the
      progression of CKD. To address this concept, we performed a longitudinal cohort
      study of 256 participants in the Seattle Kidney Study, a clinic-based study of
      CKD. Participants with an estimated GFR (eGFR) of 15-59 ml/min per 1.73 m(2) at
      baseline were eligible for the study. Physical activity was quantified using the
      Four-Week Physical Activity History Questionnaire. We used generalized estimating
      equations to test associations of physical activity with change in eGFR
      determined by longitudinal measurements of serum cystatin C. Mean baseline eGFR
      was 42 ml/min per 1.73 m(2). During a median 3.7 years of follow-up, the mean
      change in eGFRcystatin C was -7.6% per year (interquartile range, -16.8%, 4.9%
      per year). Participants who reported >150 minutes of physical activity per week
      had the lowest rate of eGFRcystatin C loss (mean -6.2% per year compared with 
      9.6% per year among inactive participants). In adjusted analyses, each 60-minute
      increment in weekly physical activity duration associated with a 0.5% slower
      decline per year in eGFR (95% confidence interval, 0.02 to 0.98; P=0.04). Results
      were similar in sensitivity analyses restricted to participants without
      cardiovascular disease or diabetes, or to participants with moderate/high
      physical function. After adjustment for eGFR at the time of questionnaire
      completion, physical activity did not associate with the incidence of ESRD (n=34
      events). In summary, higher physical activity levels associated with slower rates
      of eGFR loss in persons with established CKD. 

PMID- 24335974
TI  - New insights regarding the interrelationship of obesity, diet, physical activity,
      and kidney stones.

PMID- 24335973
TI  - Hydrogen sulfide attenuates sFlt1-induced hypertension and renal damage by
      upregulating vascular endothelial growth factor.
AB  - Soluble fms-like tyrosine kinase 1 (sFlt1), a circulating antiangiogenic protein,
      is elevated in kidney diseases and contributes to the development of
      preeclampsia. Hydrogen sulfide is a vasorelaxant and proangiogenic gas with
      therapeutic potential in several diseases. Therefore, we evaluated the potential
      therapeutic effect and mechanisms of action of hydrogen sulfide in an animal
      model of sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis
      created by adenovirus-mediated overexpression of sFlt1 in Sprague-Dawley rats. We
      injected sFlt1-overexpressing animals intraperitoneally with the hydrogen sulfide
      donor sodium hydrosulfide (NaHS) (50 umol/kg, twice daily) or vehicle (n=7 per
      group). Treatment with NaHS for 8 days significantly reduced sFlt1-induced
      hypertension, proteinuria, and glomerular endotheliosis. Measurement of plasma
      protein concentrations with ELISA revealed a reduction of free plasma sFlt1 and
      an increase of free plasma vascular endothelial growth factor (VEGF) after
      treatment with NaHS. Renal VEGF-A mRNA expression increased significantly with
      NaHS treatment. In vitro, NaHS was proangiogenic in an endothelial tube assay and
      attenuated the antiangiogenic effects of sFlt1. Stimulation of podocytes with
      NaHS resulted in both short-term VEGF release (120 minutes) and upregulation of
      VEGF-A mRNA levels (24 hours). Furthermore, pretreatment of mesenteric vessels
      with a VEGF receptor 2-neutralizing antibody significantly attenuated NaHS
      induced vasodilation. These results suggest that hydrogen sulfide ameliorates
      sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis in rats by
      increasing VEGF expression. Further studies are warranted to evaluate the role of
      hydrogen sulfide as a novel therapeutic agent for vascular disorders such as
      preeclampsia. 

PMID- 24335972
TI  - Strategies targeting cAMP signaling in the treatment of polycystic kidney
      disease.
AB  - Polycystic kidney disease (PKD) is a leading cause of ESRD worldwide. In PKD,
      excessive cell proliferation and fluid secretion, pathogenic interactions of
      mutated epithelial cells with an abnormal extracellular matrix and alternatively
      activated interstitial macrophages, and the disruption of mechanisms controlling
      tubular diameter contribute to cyst formation. Studies with animal models suggest
      that several diverse pathophysiologic mechanisms, including dysregulation of
      intracellular calcium levels and cAMP signaling, mediate these cystogenic
      mechanisms. This article reviews the evidence implicating calcium and cAMP as
      central players in a network of signaling pathways underlying the pathogenesis of
      PKD and considers the therapeutic relevance of treatment strategies targeting
      cAMP signaling. 

PMID- 24335975
TI  - Extensive podocyte loss triggers a rapid parietal epithelial cell response.
AB  - Damage to podocytes is a central pathomechanism of proteinuric kidney disease.
      However, it is not fully understood how podocyte injury evolves to progressive
      glomerulopathies such as FSGS or collapsing glomerulopathy. In particular, the
      role of parietal epithelial cells remains controversial. Here, we show that
      adriamycin induces DNA damage and podocyte lysis in mice without evidence of
      autophagy, endoplasmic reticulum stress, or necroptosis. After extensive podocyte
      loss, activated parietal cells mediated tuft re-epithelialization by two distinct
      mechanisms. In the majority of glomeruli, vacuolized parietal epithelial cells
      attached to denuded glomerular basement membrane and, occasionally, disengaged
      from the parietal basement membrane. Less frequently, parietal epithelial cells
      covered the denuded visceral basement membrane via formation of proliferative
      pseudocrescents. Notably, "visceralized" parietal epithelial cells did not
      express vascular endothelial growth factor but upregulated hypoxia-inducible
      factor 1 expression. The presence of visceralized parietal epithelial cells in
      sclerosing and collapsing lesions in a kidney biopsy from a patient with diabetes
      underscores the human relevance of our findings. In conclusion, repopulation of
      the glomerular tuft by parietal cells may represent a compensatory response to
      extensive podocyte loss. Our results suggest, however, that visceralized parietal
      epithelial cells cannot induce revascularization of the hyalinized tuft,
      resulting in hypoxic cell death and irreversible destruction of the glomerulus. 

PMID- 24335976
TI  - Activity, energy intake, obesity, and the risk of incident kidney stones in
      postmenopausal women: a report from the Women's Health Initiative.
AB  - Obesity is a strong risk factor for nephrolithiasis, but the role of physical
      activity and caloric intake remains poorly understood. We evaluated this
      relationship in 84,225 women with no history of stones as part of the Women's
      Health Initiative Observational Study, a longitudinal, prospective cohort of
      postmenopausal women enrolled from 1993 to 1998 with 8 years' median follow-up.
      The independent association of physical activity (metabolic equivalents
      [METs]/wk), calibrated dietary energy intake, and body mass index (BMI) with
      incident kidney stone development was evaluated after adjustment for
      nephrolithiasis risk factors. Activity intensity was evaluated in stratified
      analyses. Compared with the risk in inactive women, the risk of incident stones
      decreased by 16% in women with the lowest physical activity level (adjusted
      hazard ratio [aHR], 0.84; 95% confidence interval [95% CI], 0.74 to 0.97). As
      activity increased, the risk of incident stones continued to decline until
      plateauing at a decrease of approximately 31% for activity levels >=10 METs/wk
      (aHR, 0.69; 95% CI, 0.60 to 0.79). Intensity of activity was not associated with
      stone formation. As dietary energy intake increased, the risk of incident stones
      increased by up to 42% (aHR, 1.42; 95% CI, 1.02 to 1.98). However, intake <1800
      kcal/d did not protect against stone formation. Higher BMI category was
      associated with increased risk of incident stones. In summary, physical activity
      may reduce the risk of incident kidney stones in postmenopausal women independent
      of caloric intake and BMI, primarily because of the amount of activity rather
      than exercise intensity. Higher caloric intake further increases the risk of
      incident stones. 

PMID- 24335978
TI  - A human chemosensory modality to detect peptides in the nose?

PMID- 24335977
TI  - Unrecognized coral species diversity masks differences in functional ecology.
AB  - Porites corals are foundation species on Pacific reefs but a confused taxonomy
      hinders understanding of their ecosystem function and responses to climate
      change. Here, we show that what has been considered a single species in the
      eastern tropical Pacific, Porites lobata, includes a morphologically similar yet
      ecologically distinct species, Porites evermanni. While P. lobata reproduces
      mainly sexually, P. evermanni dominates in areas where triggerfish prey on
      bioeroding mussels living within the coral skeleton, thereby generating asexual
      coral fragments. These fragments proliferate in marginal habitat not colonized by
      P. lobata. The two Porites species also show a differential bleaching response
      despite hosting the same dominant symbiont subclade. Thus, hidden diversity
      within these reef-builders has until now obscured differences in trophic
      interactions, reproductive dynamics and bleaching susceptibility, indicative of
      differential responses when confronted with future climate change. 

PMID- 24335979
TI  - Evolution on the move: specialization on widespread resources associated with
      rapid range expansion in response to climate change.
AB  - Generalist species and phenotypes are expected to perform best under rapid
      environmental change. In contrast to this view that generalists will inherit the
      Earth, we find that increased use of a single host plant is associated with the
      recent climate-driven range expansion of the UK brown argus butterfly. Field
      assays of female host plant preference across the UK reveal a diversity of
      adaptations to host plants in long-established parts of the range, whereas
      butterflies in recently colonized areas are more specialized, consistently
      preferring to lay eggs on one host plant species that is geographically
      widespread throughout the region of expansion, despite being locally rare. By
      common-garden rearing of females' offspring, we also show an increase in
      dispersal propensity associated with the colonization of new sites. Range
      expansion is therefore associated with an increase in the spatial scale of
      adaptation as dispersive specialists selectively spread into new regions. Major
      restructuring of patterns of local adaptation is likely to occur across many taxa
      with climate change, as lineages suited to regional colonization rather than
      local success emerge and expand. 

PMID- 24335980
TI  - Evolutionary inevitability of sexual antagonism.
AB  - Sexual antagonism, whereby mutations are favourable in one sex and disfavourable
      in the other, is common in natural populations, yet the root causes of sexual
      antagonism are rarely considered in evolutionary theories of adaptation. Here, we
      explore the evolutionary consequences of sex-differential selection and genotype
      by-sex interactions for adaptation in species with separate sexes. We show that
      sexual antagonism emerges naturally from sex differences in the direction of
      selection on phenotypes expressed by both sexes or from sex-by-genotype
      interactions affecting the expression of such phenotypes. Moreover, modest sex
      differences in selection or genotype-by-sex effects profoundly influence the long
      term evolutionary trajectories of populations with separate sexes, as these
      conditions trigger the evolution of strong sexual antagonism as a by-product of
      adaptively driven evolutionary change. The theory demonstrates that sexual
      antagonism is an inescapable by-product of adaptation in species with separate
      sexes, whether or not selection favours evolutionary divergence between males and
      females. 

PMID- 24335981
TI  - Faunal record identifies Bering isthmus conditions as constraint to end
      Pleistocene migration to the New World.
AB  - Human colonization of the New World is generally believed to have entailed
      migrations from Siberia across the Bering isthmus. However, the limited
      archaeological record of these migrations means that details of the timing, cause
      and rate remain cryptic. Here, we have used a combination of ancient DNA, 14C
      dating, hydrogen and oxygen isotopes, and collagen sequencing to explore the
      colonization history of one of the few other large mammals to have successfully
      migrated into the Americas at this time: the North American elk (Cervus elaphus
      canadensis), also known as wapiti. We identify a long-term occupation of
      northeast Siberia, far beyond the species's current Old World distribution.
      Migration into North America occurred at the end of the last glaciation, while
      the northeast Siberian source population became extinct only within the last 500
      years. This finding is congruent with a similar proposed delay in human
      colonization, inferred from modern human mitochondrial DNA, and suggestions that
      the Bering isthmus was not traversable during parts of the Late Pleistocene. Our
      data imply a fundamental constraint in crossing Beringia, placing limits on the
      age and mode of human settlement in the Americas, and further establish the
      utility of ancient DNA in palaeontological investigations of species histories. 

PMID- 24335983
TI  - Decay of interspecific avian flock networks along a disturbance gradient in
      Amazonia.
AB  - Our understanding of how anthropogenic habitat change shapes species interactions
      is in its infancy. This is in large part because analytical approaches such as
      network theory have only recently been applied to characterize complex community
      dynamics. Network models are a powerful tool for quantifying how ecological
      interactions are affected by habitat modification because they provide metrics
      that quantify community structure and function. Here, we examine how large-scale
      habitat alteration has affected ecological interactions among mixed-species
      flocking birds in Amazonian rainforest. These flocks provide a model system for
      investigating how habitat heterogeneity influences non-trophic interactions and
      the subsequent social structure of forest-dependent mixed-species bird flocks. We
      analyse 21 flock interaction networks throughout a mosaic of primary forest,
      fragments of varying sizes and secondary forest (SF) at the Biological Dynamics
      of Forest Fragments Project in central Amazonian Brazil. Habitat type had a
      strong effect on network structure at the levels of both species and flock.
      Frequency of associations among species, as summarized by weighted degree,
      declined with increasing levels of forest fragmentation and SF. At the flock
      level, clustering coefficients and overall attendance positively correlated with
      mean vegetation height, indicating a strong effect of habitat structure on flock
      cohesion and stability. Prior research has shown that trophic interactions are
      often resilient to large-scale changes in habitat structure because species are
      ecologically redundant. By contrast, our results suggest that behavioural
      interactions and the structure of non-trophic networks are highly sensitive to
      environmental change. Thus, a more nuanced, system-by-system approach may be
      needed when thinking about the resiliency of ecological networks. 

PMID- 24335982
TI  - Rigorous approaches to species delimitation have significant implications for
      African crocodilian systematics and conservation.
AB  - Accurate species delimitation is a central assumption of biology that, in groups
      such as the Crocodylia, is often hindered by highly conserved morphology and
      frequent introgression. In Africa, crocodilian systematics has been hampered by
      complex regional biogeography and confounded taxonomic history. We used rigorous
      molecular and morphological species delimitation methods to test the hypothesis
      that the slender-snouted crocodile (Mecistops cataphractus) is composed of
      multiple species corresponding to the Congolian and Guinean biogeographic zones.
      Speciation probability was assessed by using 11 mitochondrial and nuclear genes,
      and cranial morphology for over 100 specimens, representing the full geographical
      extent of the species distribution. Molecular Bayesian and phylogenetic species
      delimitation showed unanimous support for two Mecistops species isolated to the
      Upper Guinean and Congo (including Lower Guinean) biomes that were supported by
      13 cranial characters capable of unambiguously diagnosing each species. Fossil
      calibrated phylogenetic reconstruction estimated that the species split +/- 6.5
      7.5 Ma, which is congruent with intraspecies divergence within the sympatric
      crocodile genus Osteolaemus and the formation of the Cameroon Volcanic Line. Our
      results underscore the necessity of comprehensive phylogeographic analyses within
      currently recognized taxa to detect cryptic species within the Crocodylia. We
      recommend that the community of crocodilian researchers reconsider the
      conceptualization of crocodilian species especially in the light of the
      conservation ramifications for this economically and ecologically important
      group. 

PMID- 24335984
TI  - Characterizing behavioural 'characters': an evolutionary framework.
AB  - Biologists often study phenotypic evolution assuming that phenotypes consist of a
      set of quasi-independent units that have been shaped by selection to accomplish a
      particular function. In the evolutionary literature, such quasi-independent
      functional units are called 'evolutionary characters', and a framework based on
      evolutionary principles has been developed to characterize them. This framework
      mainly focuses on 'fixed' characters, i.e. those that vary exclusively between
      individuals. In this paper, we introduce multi-level variation and thereby expand
      the framework to labile characters, focusing on behaviour as a worked example. We
      first propose a concept of 'behavioural characters' based on the original
      evolutionary character concept. We then detail how integration of variation
      between individuals (cf. 'personality') and within individuals (cf. 'individual
      plasticity') into the framework gives rise to a whole suite of novel testable
      predictions about the evolutionary character concept. We further propose a
      corresponding statistical methodology to test whether observed behaviours should
      be considered expressions of a hypothesized evolutionary character. We illustrate
      the application of our framework by characterizing the behavioural character
      'aggressiveness' in wild great tits, Parus major. 

PMID- 24335985
TI  - High strength-of-ties and low mobility enable the evolution of third-party
      punishment.
AB  - As punishment can be essential to cooperation and norm maintenance but costly to
      the punisher, many evolutionary game-theoretic studies have explored how direct
      punishment can evolve in populations. Compared to direct punishment, in which an
      agent acts to punish another for an interaction in which both parties were
      involved, the evolution of third-party punishment (3PP) is even more puzzling,
      because the punishing agent itself was not involved in the original interaction.
      Despite significant empirical studies of 3PP, little is known about the
      conditions under which it can evolve. We find that punishment reputation is not,
      by itself, sufficient for the evolution of 3PP. Drawing on research streams in
      sociology and psychology, we implement a structured population model and show
      that high strength-of-ties and low mobility are critical for the evolution of
      responsible 3PP. Only in such settings of high social-structural constraint are
      punishers able to induce self-interested agents toward cooperation, making
      responsible 3PP ultimately beneficial to individuals as well as the collective.
      Our results illuminate the conditions under which 3PP is evolutionarily adaptive
      in populations. Responsible 3PP can evolve and induce cooperation in cases where
      other mechanisms alone fail to do so. 

PMID- 24335986
TI  - The importance of invertebrates when considering the impacts of anthropogenic
      noise.
AB  - Anthropogenic noise is now recognized as a major global pollutant. Rapidly
      burgeoning research has identified impacts on individual behaviour and physiology
      through to community disruption. To date, however, there has been an almost
      exclusive focus on vertebrates. Not only does their central role in food webs and
      in fulfilling ecosystem services make imperative our understanding of how
      invertebrates are impacted by all aspects of environmental change, but also many
      of their inherent characteristics provide opportunities to overcome common issues
      with the current anthropogenic noise literature. Here, we begin by explaining why
      invertebrates are likely to be affected by anthropogenic noise, briefly reviewing
      their capacity for hearing and providing evidence that they are capable of
      evolutionary adaptation and behavioural plasticity in response to natural noise
      sources. We then discuss the importance of quantifying accurately and fully both
      auditory ability and noise content, emphasizing considerations of direct
      relevance to how invertebrates detect sounds. We showcase how studying
      invertebrates can help with the behavioural bias in the literature, the
      difficulties in drawing strong, ecologically valid conclusions and the need for
      studies on fitness impacts. Finally, we suggest avenues of future research using
      invertebrates that would advance our understanding of the impact of anthropogenic
      noise. 

PMID- 24335987
TI  - Express yourself: bold individuals induce enhanced morphological defences.
AB  - Organisms display an impressive array of defence strategies in nature. Inducible
      defences (changes in morphology and/or behaviour within a prey's lifetime) allow
      prey to decrease vulnerability to predators and avoid unnecessary costs of
      expression. Many studies report considerable interindividual variation in the
      degree to which inducible defences are expressed, yet what underlies this
      variation is poorly understood. Here, we show that individuals differing in a key
      personality trait also differ in the magnitude of morphological defence
      expression. Crucian carp showing risky behaviours (bold individuals) expressed a
      significantly greater morphological defence response when exposed to a natural
      enemy when compared with shy individuals. Furthermore, we show that fish of
      different personality types differ in their behavioural plasticity, with shy fish
      exhibiting greater absolute plasticity than bold fish. Our data suggest that
      individuals with bold personalities may be able to compensate for their risk
      prone behavioural type by expressing enhanced morphological defences. 

PMID- 24335988
TI  - Reply to A human chemo-sensory modality to detect peptides in the nose? by A.
      Natsch.

PMID- 24335990
TI  - Adaptive radiation of chemosymbiotic deep-sea mussels.

PMID- 24335989
TI  - Successful hunting increases testosterone and cortisol in a subsistence
      population.
AB  - Controversy over the adaptive significance of male hunting in subsistence
      societies hinges on the relative importance of familial provisioning and mate
      quality signalling. This paper examines the proximate and ultimate motivations of
      hunting behaviour from a neuroendocrine perspective, using salivary testosterone
      and cortisol data collected before, during and after hunting focal follows from
      31 Tsimane hunters aged 18-82 years. Despite circadian declines in hormone
      levels, testosterone and cortisol of Tsimane hunters increased at the time of a
      kill, and remained high as successful hunters returned home. Previous studies of
      hormonal changes during competitions find that high-stakes and success in the
      presence of relevant audiences result in increased neuroendocrine arousal. If men
      hunt primarily to provision their families, then an additional audience would not
      be expected to impact testosterone or cortisol, nor would the size of the animal
      killed. However, if signalling male quality by 'showing off' was a larger
      relative driver of men's hunting behaviour, one would expect greater hormonal
      response in cases where men returned with large sharable kills, especially in the
      presence of community members. Consistent with provisioning models of male
      hunting motivation, neither kill size nor encountering an audience of villagers
      while returning from hunting was associated with hormonal changes for successful
      hunters. 

PMID- 24335991
TI  - Assessment of hemoglobin threshold for packed RBC transfusion in a medical
      surgical PICU.
AB  - OBJECTIVE: Results of a large multicenter randomized clinical trial published in
      2007 demonstrated no benefit in using a liberal versus conservative RBC
      transfusion threshold in stable critically ill children. Using the conservative
      threshold decreased the number of RBC transfusions without increasing adverse
      outcomes. We aimed to determine if wide dissemination of this evidence altered
      the hemoglobin threshold used for RBC transfusions in our pediatric medical
      surgical ICU. DESIGN: Before-after retrospective cohort study using multiple
      administrative databases and chart review. SETTING: PICU serving medical and
      surgical patients. PATIENTS: All potentially stable children receiving a RBC
      transfusion in the PICU in 2006 (prepublication) and in 2009-2010
      (postpublication). Children were considered unstable and excluded if they were
      severely hypoxic, receiving renal replacement therapy, hemodynamically unstable,
      or bleeding. INTERVENTIONS: Physician education on evidence supporting hemoglobin
      transfusion thresholds in teaching conferences, staff meetings, and via e-mail.
      MEASUREMENTS AND MAIN RESULTS: In 2006, 14.6% of patients (n = 285/1,940)
      received a RBC transfusion. In 2009-2010, 12.1% of patients (n = 551/4,542)
      received a RBC transfusion. We evaluated patients transfused when they were
      potentially clinically stable, including 145 children in 2006 (191 transfusion
      days) and 266 children in 2009-2010 (369 transfusion days). We found no
      significant differences in age, sex, race, diagnoses, postoperative status,
      illness severity scores, mortality, or length of stay between these two groups.
      The median hemoglobin transfusion threshold decreased significantly from 8.0 g/dL
      (interquartile range 7.3, 8.6 g/dL) in 2006 to 7.5 g/dL (interquartile range 6.9,
      8.1 g/dL) in 2009-2010 (p = 0.001). The percentage of transfusion days using a
      hemoglobin threshold more than 7 g/dL decreased from 81% (n = 154) in 2006 to 71%
      (n = 261) in 2009-2010. CONCLUSION: Although transfusion thresholds in
      potentially stable critically ill children in our PICU significantly decreased
      after dissemination of best available evidence, 71% of patients were transfused
      at a hemoglobin threshold more than 7 g/dL.

PMID- 24335992
TI  - Anti-factor Xa assay is a superior correlate of heparin dose than activated
      partial thromboplastin time or activated clotting time in pediatric
      extracorporeal membrane oxygenation*.
AB  - OBJECTIVE: To assess the utility of activated clotting time, activated partial
      thromboplastin time, and anti-Factor Xa assay for the monitoring and dosing of
      heparin in pediatric patients requiring support with extracorporeal membrane
      oxygenation. DESIGN: Retrospective chart review. SETTING: PICU in a single,
      tertiary care, academic children's hospital. PATIENTS: Seventeen patients (age 1
      d to 13.9 yr, median 0.83 yr) managed on pulmonary and cardiac extracorporeal
      membrane oxygenation between March 2010 and August 2012 by a single surgeon.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twice daily measurements of
      anti-Factor Xa assay, activated clotting time, and activated partial
      thromboplastin time were determined from the same blood specimen. Data were
      analyzed using SAS system v9.2. Fourteen patients (82.4%) were successfully
      weaned from extracorporeal membrane oxygenation and 12 (70.6%) were discharged
      from the hospital. Pearson correlations were used to compare heparin dose and
      activated clotting time, activated partial thromboplastin time, and anti-Factor
      Xa assay. Analysis showed negative Pearson correlations in 11 of 17 patients
      between the activated clotting time and heparin, as compared with seven of 17 for
      activated partial thromboplastin time and only one for heparin and anti-Factor Xa
      assay. Only four patients had moderate to strong positive correlations between
      activated clotting time and heparin as compared with a moderate to strong
      positive correlation in 10 patients for anti-Factor Xa assay and heparin.
      CONCLUSIONS: The anti-Factor Xa assay correlated better with heparin dosing than
      activated clotting time or activated partial thromboplastin time. Activated
      clotting time has a poor correlation to heparin doses commonly associated with
      extracorporeal membrane oxygenation. In pediatric extracorporeal membrane
      oxygenation, anti-Factor Xa assay may be a more valuable monitor of heparin
      administration.

PMID- 24335993
TI  - Parental experiences and recommendations in donation after circulatory
      determination of death*.
AB  - OBJECTIVE: To describe parents' experience of organ donation decision making in
      the case of donation after circulatory determination of death. DESIGN:
      Qualitative exploratory analysis. SETTING: Participants were recruited from the
      ICU of a single children's hospital located in the western United States.
      PARTICIPANTS: Thirteen parents, 11 families who consented to donate their child's
      organs. INTERVENTIONS: Interviews (average 82 min). MEASUREMENTS AND MAIN
      RESULTS: Transcribed interviews were analyzed using the constant comparative
      method to identify themes that reflected similarities in parents' experiences.
      The themes we found included 1) factors contributing to parental decision making,
      2) under the circumstances of the child dying, and 3) donation decision and its
      impact on parental grief. Factors that influenced the decision making all related
      to the child dying, including protecting the child's body and helping the child
      to die peacefully. Finally, parents made recommendations about the organ donation
      process, including empathy, attend to end-of-life concerns, and the provision of
      relevant information for donation decisions. CONCLUSIONS: Parents' decision
      making was related directly to end-of-life experience and grief process.
      Providers need to orient to parents' end-of-life concerns to support parents'
      decision-making process and improve donation after circulatory determination of
      death procedures.

PMID- 24335994
TI  - IV enoxaparin in pediatric and cardiac ICU patients.
AB  - OBJECTIVES: To report our experience with the use of IV enoxaparin in neonatal
      and pediatric patients in the ICU. DESIGN: We performed a case control from
      January 1, 2009, to June 30, 2012, comparing patients that received IV enoxaparin
      to controls that received subcutaneous enoxaparin. Cases were matched to controls
      in a 1:2 manner. IV enoxaparin doses were infused over 30 minutes and anti-Factor
      Xa levels were drawn 4 hours after the start of the IV infusion or 4 hours after
      a subcutaneous dose. SETTING: The pediatric and cardiac ICUs of a
      tertiary/quaternary, free-standing, academic children's hospital. PATIENTS: Forty
      five neonatal and pediatric patients receiving prophylactic or therapeutic
      enoxaparin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifteen cases and
      30 controls were included. Of 15 patients, 13 received IV enoxaparin for
      treatment and two received IV enoxaparin for prophylaxis as compared with 25 of
      30 controls receiving subcutaneous enoxaparin for treatment and five receiving
      subcutaneous enoxaparin for prophylaxis. The ages for the cases ranged from 21
      days to 16 years with a median weight of 5 kg, and the ages for controls ranged
      from 10 days to 23 years with a median weight of 31 kg. The median duration of IV
      therapy was 11 days (range, 1-120 d) and the median duration for subcutaneous
      therapy was 15 days (range, 3-85 d). The mean initial IV dose was 1.14 +/- 0.38
      mg/kg/dose q12h, and the mean initial subcutaneous dose was 0.85 +/- 0.2
      mg/kg/dose subcutaneous q12h (p = 0.003). The mean therapeutic IV dose was 1.31
      +/- 0.52 mg/kg/dose q12h, and the mean therapeutic subcutaneous dose was 0.9 +/-
      0.3 mg/kg/dose q12h (p = 0.016). There were no adverse events reported related to
      bleeding, thrombosis, or hypersensitivity in any of the cases or controls
      evaluated. CONCLUSION: The pharmacodynamics of a 30-minute IV enoxaparin infusion
      was found to produce therapeutic 4 hour anti-Factor Xa levels similar to
      subcutaneous doses. Although this was a small study, there were no adverse
      events, suggesting the safety profile of IV enoxaparin may be similar to
      subcutaneous dosing with the added benefit of less pain associated with IV
      dosing. These findings suggest that IV enoxaparin may be a viable option for
      anticoagulating critically ill children and its use warrants further study.

PMID- 24335995
TI  - Pediatric code events: does in-house intensivist coverage improve outcomes?*.
AB  - OBJECTIVES: A change in our children's hospital coverage model to providing full
      time in-house supervision by intensivists allowed us to evaluate the impact of
      this change on patient safety outcomes. Our aim was to determine whether in-house
      attending coverage influenced the prevalence and outcomes of pediatric code
      events. DESIGN: We conducted a retrospective review of all code events between
      October 2005 and October 2007 (before in-house intensivist supervision) and
      compared the prevalence, interventions, and outcomes of these codes with those
      occurring between April 2008 and April 2010 (after in-house intensivist
      supervision). A code event was defined as any activation of the code system.
      SETTING: One hundred eighty-seven bed children's hospital. SUBJECTS: All children
      with code events. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were
      99 codes during these two periods: 39 codes occurring prior to in-house
      intensivist coverage (of which eight on the ward and 31 in the ICU) and 60
      occurring following in-house attending coverage (30 on the ward and 30 in the
      ICU). Survival was significantly improved following the implementation of in
      house coverage (odds ratio, 4.3; 95% CI, 1.7-10.8; p = 0.003). There was no
      significant change in the overall rate of codes during these two periods (0.82
      codes/1,000 patient-days before implementation vs 1.17 codes/1,000 patient-days
      after implementation). However, there were significantly more codes on the ward
      following in-house intensivist coverage (0.2 codes/1,000 patient-days before
      implementation vs 0.71 codes/1,000 patient-days after implementation; p = 0.013).
      An intensivist was significantly more likely to be present during these events
      (odds ratio, 28; 95% CI, 3-273; p = 0.001); however, the acuity of the children
      with codes on the ward was significantly lower during the in-house coverage
      period (p = 0.001). There were no changes in the rate or outcomes of codes
      occurring in the ICU with this change in coverage. CONCLUSIONS: In the period
      following implementation of in-house intensivist supervision, children with code
      events were more likely to survive to hospital discharge. Having an intensivist
      in-house 24 hr/d, 7 d/wk may be associated with improved outcomes in hospitalized
      children.

PMID- 24335996
TI  - The smooth muscle-selective RhoGAP GRAF3 is a critical regulator of vascular tone
      and hypertension.
AB  - Although hypertension is a worldwide health issue, an incomplete understanding of
      its aetiology has hindered our ability to treat this complex disease. Here we
      identify arhgap42 (also known as GRAF3) as a Rho-specific GAP expressed
      specifically in smooth muscle cells (SMCs) in mice and humans. We show that GRAF3
      deficient mice exhibit significant hypertension and increased pressor responses
      to angiotensin II and endothelin-1; these effects are prevented by treatment with
      the Rho-kinase inhibitor, Y27632. RhoA activity and myosin light chain
      phosphorylation are elevated in GRAF3-depleted SMCs in vitro and in vivo, and
      isolated vessel segments from GRAF3-deficient mice show increased contractility.
      Taken together, our data indicate that GRAF3-mediated inhibition of RhoA activity
      in vascular SMCs is necessary for maintaining normal blood pressure homoeostasis.
      Moreover, these findings provide a potential mechanism for a hypertensive locus
      recently identified within arhgap42 and provide a foundation for the future
      development of innovative hypertension therapies. 

PMID- 24335997
TI  - Impact of intercurrent respiratory infections on lung health in infants born <29
      weeks with bronchopulmonary dysplasia.
AB  - OBJECTIVE: Assess the impact of intercurrent respiratory infections in infants
      <29 weeks gestational age (GA). STUDY DESIGN: A retrospective cohort study of 111
      infants born <29 weeks GA, controlling for bronchopulmonary dysplasia (BPD)
      severity and assessing pulmonary health over the first year of life through
      oxygen, diuretic and inhaled steroid use. RESULT: Regression analysis showed
      viral infections increased oxygen use (odds ratio (OR) of 15.5 (confidence
      interval (CI)=3.4, 71.3)). The trend test showed increasing numbers of viral
      infections were associated with increased oxygen (OR (95% CI)=6.4 (2.3 to 17.4),
      P=0.0003), diuretic (OR (95% CI)=2.4 (1.1to 5.2), P=0.02) and inhaled steroid use
      (OR (95% CI)=2.2 (1.003 to 5.2), P=0.049), whereas bacterial infections were not.
      CONCLUSION: Viral infections caused more long-term pulmonary morbidity/mortality
      than bacterial infections on premature lung health, even when controlling for
      BPD.

PMID- 24335998
TI  - Splenectomy prior to allogeneic hematopoietic SCT increases the risk of post
      transplant lymphoproliferative disease.

PMID- 24335999
TI  - Total leukoderma and leukotrichia in a child after hematopoietic SCT: report of a
      case and review of the literature.

PMID- 24336000
TI  - Quantum coherence induces pulse shape modification in a semiconductor optical
      amplifier at room temperature.
AB  - Coherence in light-matter interaction is a necessary ingredient if light is used
      to control the quantum state of a material system. Coherent effects are firmly
      associated with isolated systems kept at low temperature. The exceedingly fast
      dephasing in condensed matter environments, in particular at elevated
      temperatures, may well erase all coherent information in the material at
      timescales shorter than a laser excitation pulse. Here we show for an ensemble of
      semiconductor quantum dots that even in the presence of ultrafast dephasing, for
      suitably designed condensed matter systems quantum-coherent effects are robust
      enough to be observable at room temperature. Our conclusions are based on an
      analysis of the reshaping an ultrafast laser pulse undergoes on propagation
      through a semiconductor quantum dot amplifier. We show that this pulse
      modification contains the signature of coherent light-matter interaction and can
      be controlled by adjusting the population of the quantum dots via electrical
      injection. 

PMID- 24336001
TI  - Morphology and size of stem cells from mouse and whale: observational study.
AB  - OBJECTIVE: To compare the morphology and size of stem cells from two mammals of
      noticeably different body size. DESIGN: Observational study. SETTING: The
      Netherlands. PARTICIPANTS: A humpback whale (Megaptera novaeangliae) and a
      laboratory mouse (Mus musculus). MAIN OUTCOME MEASURES: Morphology and size of
      mesenchymal stem cells from adipose tissue. RESULTS: Morphologically, mesenchymal
      stem cells of the mouse and whale are indistinguishable. The average diameter of
      50 mesenchymal stem cells from the mouse was 28 (SD 0.86) um and 50 from the
      whale was 29 (SD 0.71) um. The difference in cell size between the species was
      not statistically significant. Although the difference in bodyweight between the
      species is close to two million-fold, the mesenchymal stem cells of each were of
      similar size. CONCLUSIONS: The mesenchymal stem cells of whales and mice are
      alike, in both morphology and size.

PMID- 24336002
TI  - Tremor.

PMID- 24336003
TI  - How big is the US healthcare lobby?

PMID- 24336004
TI  - Red flags for back pain.

PMID- 24336005
TI  - A third of general practices in England's first wave of inspections failed on
      essential standards.

PMID- 24336006
TI  - Local government is given help to prioritise public health schemes.

PMID- 24336007
TI  - Nonalcoholic fatty liver disease is associated with low HDL cholesterol and
      coronary angioplasty in patients with type 2 diabetes.
AB  - BACKGROUND: There is evidence that nonalcoholic fatty liver disease (NAFLD) is
      associated with increased cardiovascular risk. In this study we examined factors
      associated with the presence of NAFLD and the prevalence of macroangiopathy in
      patients with type 2 diabetes. MATERIAL AND METHODS: Subjects were 101
      consecutive patients with type 2 diabetes: 72 with NAFLD and 29 free of NAFLD.
      NAFLD was diagnosed by ultrasonography. Serum lipids were measured enzymatically
      and glycated hemoglobin HbA1c was measured by HPLC. RESULTS: The mean age of
      patients was 53.1 +/- 10.4 in the NAFLD group and 44.9 +/- 10.9 years in patients
      without NAFLD (p<0.001). The mean duration of diabetes was 10 +/- 6.3 years in
      patients with NAFLD and 15.1 +/- 7.8 years in those without NAFLD (p<0.001). Mean
      values of glycated hemoglobin A1c were similar in both groups. Patients with
      NAFLD were characterized by a significantly higher prevalence of coronary
      angioplasty (20.8% vs. 0%, p=0.008). Overweight and obesity were observed in a
      higher percentage of patients with NAFLD (p<0.001). Patients with NAFLD were
      characterized by significantly higher values of alanine transaminase (p=0.033),
      and lower serum concentrations of HDL-cholesterol (p<0.001) and creatinine
      (p=0.034). Logistic regression analysis (p<0.001) revealed that NAFLD was
      positively associated with waist circumference above normal (women >80 cm, men
      >94 cm) (p=0.0083) and alanine transaminase activity (p=0.0164), and negatively
      with creatinine concentration (p=0.0226). In a second logistic regression model
      (p<0.001), waist circumference (p<0.007) and total cholesterol (p<0.008) were
      positive predictors, while HDL-C (p<0.003) was a negative predictor of NAFLD.
      CONCLUSIONS: The results of the study suggest that NAFLD is associated with
      visceral obesity and low HDL-cholesterol in patients with type 2 diabetes.

PMID- 24336008
TI  - Finger pulse oximetry detects an intense congestion: A case report.

PMID- 24336009
TI  - Concordance between inflammation at physical examination and on MRI in patients
      with early arthritis.
AB  - BACKGROUND: MRI is increasingly used to measure inflammation in rheumatoid
      arthritis (RA) research, but the correlation to clinical assessment is
      unexplored. This study determined the association and concordance between
      inflammation of small joints measured with MRI and physical examination. METHODS:
      179 patients with early arthritis underwent a 68 tender joint count and 66
      swollen joint count and 1.5T MRI of MCP (2-5), wrist and MTP (1-5) joints at the
      most painful side. Two readers scored synovitis and bone marrow oedema (BME)
      according to the OMERACT RA MRI scoring method and assessed tenosynovitis. The
      MRI data were first analysed continuously and then dichotomised to analyse the
      concordance with inflammation at joint examination. RESULTS: 1790 joints of 179
      patients were studied. Synovitis and tenosynovitis on MRI were independently
      associated with clinical swelling, in contrast to BME. In 86% of the swollen MCP
      joints and in 92% of the swollen wrist joints any inflammation on MRI was
      present. In 27% of the non-swollen MCP joints and in 66% of the non-swollen wrist
      joints any MRI inflammation was present. Vice versa, of all MCP, wrist and MTP
      joints with inflammation on MRI 64%, 61% and 77%, respectively, were not swollen.
      BME, also in case of severe lesions, occurred frequently in clinically non
      swollen joints. Similar results were observed for joint tenderness. CONCLUSIONS:
      Inflammation on MRI is not only present in clinically swollen but also in non
      swollen joints. In particular BME occurred in clinically non-inflamed joints. The
      relevance of subclinical inflammation for the disease course is a subject for
      further studies.

PMID- 24336010
TI  - High incidence of disease recurrence after discontinuation of disease-modifying
      antirheumatic drug treatment in patients with psoriatic arthritis in remission.
AB  - OBJECTIVE: To investigate the possibility of drug-free remission in patients with
      psoriatic arthritis (PsA) in continuous remission. METHODS: Prospective
      observational study in disease-modifying antirheumatic drug (DMARD)-treated PsA
      patients in continuous disease remission (no musculoskeletal symptoms, no or
      minimal skin/nail disease) for at least 6 months. Demographic, disease-specific
      and ultrasound parameters were assessed at baseline. DMARDs (traditional or
      biologic) were discontinued at the initial visit, and patients were followed for
      a maximum of 6 months for recurrence of disease. RESULTS: 26 patients
      (methotrexate monotherapy: N=14; tumour necrosis factor inhibitors: N=12) with a
      mean age of 55.2 years, absence of musculoskeletal symptoms and minimal skin
      disease (mean Psoriasis Area Severity Index (PASI): 0.21) were enrolled.
      Incidence of recurrence of disease was high (N=20, 76.9%) and occurred rapidly
      (74.50+/-51.72 days) after treatment discontinuation. Male PsA patients were
      significantly more likely to lose remission. Long disease duration, more severe
      skin involvement and the presence of synovial hypertrophy by ultrasonographic
      examination at baseline decreased the likelihood for drug-free remission.
      Reinitiation of DMARDs promptly restored remission in all PsA patients with
      recurrence of disease. CONCLUSIONS: This study shows that the chance to reach
      drug-free remission in PsA patients is low. Discontinuation of DMARD therapy
      cannot be recommended in patients with PsA.

PMID- 24336011
TI  - The cardioprotective effects of novel Na+/H+ exchanger inhibitor TY-51924 on
      ischemia/reperfusion injury.
AB  - The inhibitory effects of sodium 3-guanidinocarbonyl-2-methyl-6,7,8,9-tetrahydro
      5H-cyclohepta[b]pyridine-9-ylmethyl sulfate monoethanolate (TY-51924) are
      selective for Na(+)/H(+) exchanger (NHE)-1 in PS120 cells expressing human NHE
      isoforms assayed by NH(4)Cl prepulse technique. The median inhibitory
      concentrations (micromolar) of TY-51924 were 0.095 +/- 0.008 (NHE-1), 0.621 +/-
      0.093 (NHE-2), and >100 (NHE-3). In anesthetized dogs subjected to 90 minutes
      ischemia/300 minutes reperfusion, intravenous bolus TY-51924 at 5 and 10 mg/kg
      administered 5 minutes before reperfusion reduced infarct size. The infarct size
      reduction ratios of TY-51924 at 5 and 10 mg/kg versus vehicle were 32.8% and
      52.4%, respectively. But TY-51924 at 10 mg/kg administered 10 minutes after
      reperfusion did not reduce infarct size. In 2-step intravenous infusion initiated
      15 minutes before reperfusion, TY-51924 at low dose (3.8 mg/kg per 5 minutes,
      then 6.2 mg/kg per 20 minutes) and at high dose (7.6 mg/kg per 5 minutes, then
      12.4 mg/kg per 20 minutes) reduced infarct size. The infarct size reduction
      ratios of TY-51924 at 10 and 20 mg/kg versus vehicle were 39.2% and 51.7%,
      respectively; plasma drug concentrations at reperfusion were 16.8 and 38.8
      MUg/mL, respectively. This indicates that maintaining a plasma drug concentration
      of >20 MUg/mL at reperfusion enables TY-51924 to reduce infarct size by
      inhibiting the NHE, which is activated during the early period of reperfusion.

PMID- 24336012
TI  - Effects of clopidogrel therapy on oxidative stress, inflammation, vascular
      function, and progenitor cells in stable coronary artery disease.
AB  - BACKGROUND: Traditional cardiovascular risk factors lead to endothelial injury
      and activation of leukocytes and platelets that initiate and propagate
      atherosclerosis. We proposed that clopidogrel therapy in patients with stable
      coronary artery disease imparts a pleiotropic effect that extends beyond
      antiplatelet aggregation to other atheroprotective processes. METHODS: Forty-one
      subjects were randomized in a double-blind, placebo-controlled, crossover study
      to receive either clopidogrel 75 mg daily or placebo for 6 weeks and then
      transitioned immediately to the other treatment for an additional 6 weeks. We
      assessed (1) endothelial function as flow-mediated dilation of the brachial
      artery, (2) arterial stiffness and central augmentation index using applanation
      tonometry, (3) vascular function as fingertip reactive hyperemia index, (4)
      inflammation by measuring plasma CD40 ligand and serum high-sensitivity c
      reactive protein levels, (5) oxidative stress by measuring plasma aminothiols,
      and (6) circulating progenitor cells, at baseline and at the end of each 6-week
      treatment period. RESULTS: Clopidogrel therapy resulted in a significant
      reduction in soluble CD40 ligand (P = 0.03), a prothrombotic and proinflammatory
      molecule derived mainly from activated platelets. However, clopidogrel therapy
      had no effect on endothelial function, arterial stiffness, inflammatory and
      oxidative stress markers, or progenitor cells. CONCLUSIONS: Our findings suggest
      a solitary antiplatelet effect of clopidogrel therapy in patients with stable
      coronary artery disease, with no effect on other subclinical markers of
      cardiovascular disease risk.

PMID- 24336013
TI  - Revascularization versus medical treatments in stable coronary artery disease:
      predicting the future of novel drug therapies for stable angina.
AB  - Over the past 2 decades, drug therapy of patients with stable angina pectoris has
      improved, with a marked impact on the hard clinical outcomes of mortality and
      myocardial infarction. In contrast, recent trials have not demonstrated
      beneficial effects of revascularization on mortality. However, in the large
      trials that compared medical treatment with percutaneous coronary intervention
      (PCI) or surgery, high-risk patients, such as those with severe 3-vessel disease
      with or without left ventricular dysfunction, were excluded. In the COURAGE and
      FAME 2 trials, the only difference between the PCI and medical therapy groups was
      a higher rate of revascularization in the latter. Similar findings were made in
      studies comparing medical treatment with coronary surgery. New pharmacological
      approaches are being developed to further delay the progression of
      atherosclerosis. These include new lipid-lowering drugs acting in concert with
      statins (cholesteryl ester transfer protein inhibitors, proprotein convertase
      subtilisin/kexin type 9 inhibitors), aldosterone antagonists, colchicine,
      methotrexate, and interleukin-1 inhibitors. In conclusion, from the available
      data, PCI and coronary surgery have not been shown to improve hard end points and
      routine use of invasive revascularization should be avoided in patients with
      chronic stable angina. Evidence-based secondary prevention remains the most
      important approach.

PMID- 24336015
TI  - Enhanced vascular PI3K/Akt-NOX signaling underlies the peripheral NMDAR-mediated
      pressor response in conscious rats.
AB  - The molecular mechanisms for peripheral N-methyl-D-aspartate receptor (NMDAR)
      mediated vascular oxidative stress and pressor response are not known. We
      conducted integrative (in vivo) and ex vivo biochemical studies to test the
      hypothesis that reactive oxygen species (ROS)-dependent calcium influx, triggered
      by the activation of vascular kinases, underlies the NMDAR-mediated pressor
      response. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K)/Akt
      (wortmannin, 15 MUg/kg), protein kinase C (chelerythrine: 5 mg/kg, intravenous),
      Ca2+ influx (nifedipine, 0.35 or 0.75 mg/kg), or NADPH oxidase (NOX: apocynin, 5
      mg/kg) attenuated the peripheral NMDAR-mediated pressor response in conscious
      male Sprague-Dawley rats. NMDAR activation enhanced the phosphorylation of Akt,
      ERK1, JNK and p38 (Western blot), and NOX activity in vascular tissues collected
      during the pressor response caused by NMDA infusion (180 MUg.kg-1.min-1, 30
      minutes). Furthermore, ex vivo studies showed that wortmannin, chelerythrine, or
      apocynin abrogated the NMDAR-mediated vascular nitric oxide (NO) and ROS
      generation and NOX activation in the vasculature. These findings implicate
      vascular PI3K/Akt-protein kinase C signaling in the peripheral NMDAR-mediated
      increases in vascular NO and NOX activation (ROS), which ultimately lead to
      calcium influx and pressor response in conscious rats.

PMID- 24336014
TI  - Heart failure and loss of metabolic control.
AB  - Heart failure is a leading cause of morbidity and mortality worldwide, currently
      affecting 5 million Americans. A syndrome defined on clinical terms, heart
      failure is the end result of events occurring in multiple heart diseases,
      including hypertension, myocardial infarction, genetic mutations and diabetes,
      and metabolic dysregulation, is a hallmark feature. Mounting evidence from
      clinical and preclinical studies suggests strongly that fatty acid uptake and
      oxidation are adversely affected, especially in end-stage heart failure.
      Moreover, metabolic flexibility, the heart's ability to move freely among diverse
      energy substrates, is impaired in heart failure. Indeed, impairment of the
      heart's ability to adapt to its metabolic milieu and associated metabolic
      derangement are important contributing factors in the heart failure pathogenesis.
      Elucidation of molecular mechanisms governing metabolic control in heart failure
      will provide critical insights into disease initiation and progression, raising
      the prospect of advances with clinical relevance.

PMID- 24336016
TI  - Benefits from new ADP antagonists as compared with clopidogrel in patients with
      stable angina or acute coronary syndrome undergoing invasive management: a meta
      analysis of randomized trials.
AB  - AIMS: New P2Y12 receptor inhibitors have provided new and more potent
      antiplatelet strategies, although raising several concerns on possible increase
      of bleedings. The aim of current meta-analysis was to evaluate the efficacy and
      safety of new adenosine diphosphate (ADP) receptor antagonists as compared with
      clopidogrel in elective or ACS patients managed invasively. METHODS AND RESULTS:
      Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions
      abstracts were scanned for randomized trials comparing new ADP antagonists with
      clopidogrel in patients with acute coronary syndromes or stable angina. Primary
      endpoint was mortality. Secondary endpoints were: (1) nonfatal myocardial
      infarction (MI), (2) recurrent ischemia symptoms or ischemia-driven
      revascularization (RI/IDR), (3) stent thrombosis (ST), and (4) safety endpoints,
      defined as for TIMI major bleeding criteria. A total of 8 randomized clinical
      trials were finally included, for a total population of 67,851 patients. Mean
      follow-up was 7.6 months, ranging from 48 hours to 30 months. New ADP antagonists
      significantly reduced mortality {3.1% vs. 3.6%, odds ratio [OR] [95% confidence
      interval (CI)], 0.86 [0.79-0.94], P = 0.0008, P(het) = 0.18}, with greater impact
      of oral drugs. Similar benefits were found for MI [6.1% vs. 7%; OR (95% CI)
      (random-effect model) = 0.88 (0.79-0.98), P = 0.01, P(het) = 0.02], RI [2.7% vs.
      3.1%; OR (95% CI) = 0.85 (0.77-0.93), P = 0.0005, P(het) = 0.09], or ST [1.1% vs.
      1.7%; OR (95% CI) = 0.60 (0.51-0.71), P < 0.00001, P(het) = 0.13]. By meta
      regression analysis, no relationship was observed between benefits in mortality,
      new MI, RI, and ST with new ADP antagonists and patients' risk profile [beta (95%
      CI) = -0.01 [-0.30 to 0.27], P = 0.94; beta (95% CI) = -0.05 [-1.49 to 1.43], P =
      0.96); beta (95% CI) = 0.19 (-0.18 to 0.57), P = 0.31, and beta (95% CI) = -0.08
      (-0.86 to 0.70), P = 0.84, respectively]. CONCLUSIONS: Present meta-analysis
      shows that the new ADP antagonists prasugrel, ticagrelor, and cangrelor are
      associated to significant reduction of mortality, reinfarction, RI, and ST
      respect to clopidogrel alone, without significant increase in bleeding
      complications.

PMID- 24336017
TI  - A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial
      injury after ischemia-reperfusion in the mouse.
AB  - BACKGROUND: The formation of the NLRP3 inflammasome in the heart during acute
      myocardial infarction amplifies the inflammatory response and mediates further
      damage. Glyburide has NLRP3 inhibitory activity in vitro but requires very high
      doses in vivo, associated with hypoglycemia. The aim of this study was to measure
      the effects on the NLRP3 inflammasome of 16673-34-0, an intermediate substrate
      free of the cyclohexylurea moiety, involved in insulin release. METHODS AND
      RESULTS: We synthesized 16673-34-0 (5-chloro-2-methoxy-N-[2-(4
      sulfamoylphenyl)ethyl]benzamide) that displayed no effect on glucose metabolism.
      HL-1 cardiomyocytes were treated with lipopolysaccharide and ATP to induce the
      formation of the NLRP3 inflammasome, measured as increased caspase-1 activity and
      cell death, and 16673-34-0 prevented such effects. 16673-34-0 was well tolerated
      with no effects on the glucose levels in vivo. Treatment with 16673-34-0 in a
      model of acute myocardial infarction because of ischemia and reperfusion
      significantly inhibited the activity of inflammasome (caspase-1) in the heart by
      90% (P < 0.01) and reduced infarct size, measured at pathology (by >40%, P <
      0.01) and with troponin I levels (by >70%, P < 0.01). CONCLUSIONS: The small
      molecule 16673-34-0, an intermediate substrate in the glyburide synthesis free of
      the cyclohexylurea moiety, inhibits the formation of the NLRP3 inflammasome in
      cardiomyocytes and limits the infarct size after myocardial ischemia-reperfusion
      in the mouse, without affecting glucose metabolism.

PMID- 24336018
TI  - Sodium ferulate protects against daunorubicin-induced cardiotoxicity by
      inhibition of mitochondrial apoptosis in juvenile rats.
AB  - Daunorubicin (DNR) is a widely used chemotherapeutic agent; however, its clinical
      use is limited because of its cardiotoxicity. This study was aimed to investigate
      the protective effect of sodium ferulate (SF), an effective component from
      traditional Chinese herbs, against DNR-induced cardiotoxicity in juvenile rats.
      DNR was administered intraperitoneally to rats at the dosage of 2.5 mg.kg(-1).wk(
      1) for 5 consecutive weeks (cumulative dose of 12.5 mg/kg) or in combination with
      intraperitoneal injection of SF at 50 mg.kg(-1).d(-1) over a period of 30 days.
      The animals were killed 6 days after the last injection of DNR. SF significantly
      ameliorated the DNR-induced cardiac dysfunction, structural damage of the
      myocardium, and release of lactate dehydrogenase and creatine kinase. Treatment
      with SF also reversed DNR-induced oxidative stress as evidenced by a decrease in
      malondialdehyde levels with a concomitant increase in myocardical superoxide
      dismutase activities. Furthermore, SF afforded significant cardioprotection
      against DNR-induced apoptosis in vivo and effectively suppressed the complex
      mitochondrion-dependent apoptotic signaling triggered by DNR. This study
      indicates that SF may improve cardiac function by inhibition of oxidative stress
      and apoptosis, thus providing a beneficial effect on the prevention of DNR
      induced cardiotoxicity.

PMID- 24336019
TI  - Volcanic ash and daily mortality in Sweden after the Icelandic volcano eruption
      of May 2011.
AB  - In the aftermath of the Icelandic volcano Grimsvotn's eruption on 21 May 2011,
      volcanic ash reached Northern Europe. Elevated levels of ambient particles (PM)
      were registered in mid Sweden. The aim of the present study was to investigate if
      the Grimsvotn eruption had an effect on mortality in Sweden. Based on PM
      measurements at 16 sites across Sweden, data were classified into an ash exposed
      data set (Ash area) and an unexposed data set (No ash area). Data on daily all
      cause mortality were obtained from Statistics Sweden for the time period 1 April
      through 31 July 2011. Mortality ratios were calculated as the ratio between the
      daily number of deaths in the Ash area and the No ash area. The exposure period
      was defined as the week following the days with elevated particle concentrations,
      namely 24 May through 31 May. The control period was defined as 1 April through
      23 May and 1 June through 31 July. There was no absolute increase in mortality
      during the exposure period. However, during the exposure period the mean
      mortality ratio was 2.42 compared with 2.17 during the control period, implying a
      relatively higher number of deaths in the Ash area than in the No ash area. The
      differences in ratios were mostly due to a single day, 31 May, and were not
      statistically significant when tested with a Mann-Whitney non-parametric test (p
      > 0.3). The statistical power was low with only 8 days in the exposure period (24
      May through 31 May). Assuming that the observed relative differences were not due
      to chance, the results would imply an increase of 128 deaths during the exposure
      period 24-31 May. If 31 May was excluded, the number of extra deaths was reduced
      to 20. The results of the present study are contradicting and inconclusive, but
      may indicate that all-cause mortality was increased by the ash-fall from the
      Grimsvotn eruption. Meta-analysis or pooled analysis of data from neighboring
      countries might make it possible to reach sufficient statistical power to study
      effects of the Grimsvotn ash on morbidity and mortality. Such studies would be of
      particular importance for European societies preparing for future large scale
      volcanic eruptions in Iceland. 

PMID- 24336020
TI  - Using formative research to design a behavior change strategy to increase the use
      of improved cookstoves in peri-urban Kampala, Uganda.
AB  - Household air pollution from cooking with biomass fuels negatively impacts
      maternal and child health and the environment, and contributes to the global
      burden of disease. In Uganda, nearly 20,000 young children die of household air
      pollution-related pneumonia every year. Qualitative research was used to identify
      behavioral determinants related to the acquisition and use of improved cookstoves
      in peri-urban Uganda. Results were used to design a behavior change strategy for
      the introduction of a locally-fabricated top-lit updraft gasifier (TLUD) stove in
      Wakiso district. A theoretical framework--opportunity, ability, and motivation-
      was used to guide the research and behavior change strategy development.
      Participants consistently cited financial considerations as the most influential
      factor related to improved cookstove acquisition and use. In contrast,
      participants did not prioritize the potential health benefits of improved
      cookstoves. The theoretical framework, research methodology, and behavior change
      strategy design process can be useful for program planners and researchers
      interested in identifying behavioral determinants and designing and evaluating
      improved cookstove interventions.

PMID- 24336021
TI  - Challenges to achieving sustainable sanitation in informal settlements of Kigali,
      Rwanda.
AB  - Like most cities in developing countries, Kigali is experiencing rapid
      urbanisation leading to an increase in the urban population and rapid growth in
      the size and number of informal settlements. More than 60% of the city's
      population resides in these settlements, where they experience inadequate and
      poor quality urban services including sanitation. This article discusses the
      issues and constraints related to the provision of sustainable sanitation in the
      informal settlements in Kigali. Two informal settlements (Gatsata and Kimisagara)
      were selected for the study, which used a mixed method approach for data
      collection. The research found that residents experienced multiple problems
      because of poor sanitation and that the main barrier to improved sanitation was
      cost. Findings from this study can be used by the city authorities in the
      planning of effective sanitation intervention strategies for communities in
      informal settlements. 

PMID- 24336023
TI  - HLA alleles and hypersensitivity to carbamazepine: an updated systematic review
      with meta-analysis.
AB  - OBJECTIVE: A considerable heterogeneity exists in the literature on the role of
      different HLA alleles in carbamazepine (CBZ)-induced cutaneous adverse drug
      reactions (cADRs) of varying severity among diverse ethnic groups. The aim of the
      present study was to understand and summarize this heterogeneity and evaluate the
      contribution of common HLA alleles to susceptibility to cADRs in patients treated
      with CBZ through a meta-analysis. MATERIALS AND METHODS: A literature search of
      Embase, Medline, Web of Knowledge, and Cochrane database of systematic reviews
      was performed up to 28 September 2013. RESULTS: A total of 20 reports were
      identified as eligible studies, which included 720 CBZ-intolerant [Stevens
      Johnson syndrome and toxic epidermal necrolysis (bullous lesions): n=277;
      hypersensitivity syndrome/maculopapular exanthema (nonbullous lesions): n=359;
      others: n=84], 1512 CBZ-tolerant, and 1113 normal controls. We observed HLA
      A*3101 and HLA-B*1502 as risk markers and HLA-B*4001 as a protective marker for
      susceptibility to cADRs when comparing intolerant with tolerant patients.
      Stratification by clinical outcome showed HLA-B*1502 and HLA-B*1511 as risk and
      HLA-A*2402 as protective markers for bullous lesions in the Asians [HLA-B*1502:
      odds ratio (OR)=80.70; 95% confidence interval (CI)=45.62-142.77; P=1.8*10(-51);
      I(2)=33%, HLA-B*1511: OR=17.43; 95% CI=3.12-97.40; P=1.1*10(-3); I(2)=0%, HLA
      A*2402: OR=0.27; 95% CI=0.11-0.64; P=2.7*10(-3); I(2)=0%]. Furthermore, HLA
      A*3101 was observed to be a universal risk marker, irrespective of cADR type [OR
      (bullous lesions)=5.65; 95% CI =2.70-11.78; P=4.03*10(-6); I(2)=49%, OR
      (nonbullous lesions)=8.58; 95% CI=5.55-13.28; P=4.46*10(-22); I(2)=0%].
      Sensitivity analysis showed HLA-B*4001 as a protective marker in Chinese
      population for showing bullous lesions (OR=0.14; 95% CI=0.06-0.32; P=3.2*10(-6);
      I(2)=0%). CONCLUSION: In summary, our meta-analysis showed the presence of HLA
      alleles contributing toward risk of as well as protection against various CBZ
      induced cADRs.

PMID- 24336022
TI  - UTX coordinates steroid hormone-mediated autophagy and cell death.
AB  - Correct spatial and temporal induction of numerous cell type-specific genes
      during development requires regulated removal of the repressive histone H3 lysine
      27 trimethylation (H3K27me3) modification. Here we show that the H3K27me3
      demethylase dUTX is required for hormone-mediated transcriptional regulation of
      apoptosis and autophagy genes during ecdysone-regulated programmed cell death of
      Drosophila salivary glands. We demonstrate that dUTX binds to the nuclear hormone
      receptor complex Ecdysone Receptor/Ultraspiracle, and is recruited to the
      promoters of key apoptosis and autophagy genes. Salivary gland cell death is
      delayed in dUTX mutants, with reduced caspase activity and autophagy that
      coincides with decreased apoptosis and autophagy gene transcripts. We further
      show that salivary gland degradation requires dUTX catalytic activity. Our
      findings provide evidence for an unanticipated role for UTX demethylase activity
      in regulating hormone-dependent cell death and demonstrate how a single
      transcriptional regulator can modulate a specific complex functional outcome
      during animal development. 

PMID- 24336024
TI  - Characteristic changes in microbial community composition and expression of
      innate immune genes in acute appendicitis.
AB  - Appendicitis represents a common and severe gastrointestinal illness in younger
      individuals worldwide. The disease is characterized by an excessive inflammatory
      response and it is believed that bacterial overgrowth due to blockage of the
      appendix lumen might be involved. Despite the high incidence, only limited data
      on the pathophysiological changes exist; in particular, the innate immune
      responses involved are largely unknown. Real-time PCR analysis of tissue samples
      from inflamed and normal appendices demonstrated differentially regulated
      expression patterns of epithelial-derived antimicrobial peptides (AMP). The alpha
      defensins human neutrophil peptides 1-3, HD5 and HD6, as well as the two beta
      defensins, human beta-defensins (hBD)-2 and hBD-3, were up-regulated, whereas hBD
      1 was down-regulated in acute appendicitis. Expression of upstream regulators of
      AMP expression, NOD-2 and TLRs 1, 2, 4, 5, 7, 8 and 10 was significantly
      increased as detected by real-time PCR. Finally, we confirmed the involvement of
      the pro-inflammatory cytokines IL-1beta and IL-8, and detected characteristic
      changes in microbial community composition in appendicitis tissue specimens by
      16S rDNA based detection techniques. In this study, we demonstrate a differential
      regulation of the innate immune system along with an altered bacterial diversity
      in acute appendicitis.

PMID- 24336026
TI  - Maternal exposure to bisphenol-A and fetal growth restriction: a case-referent
      study.
AB  - We conducted a case-referent study of the effect of exposure to bisphenol-A on
      fetal growth in utero in full-term, live-born singletons in Alberta, Canada.
      Newborns <10 percentile of expected weight for gestational age and sex were
      individually matched on sex, maternal smoking and maternal age to referents with
      weight appropriate to gestational age. Exposure of the fetus to bisphenol-A was
      estimated from maternal serum collected at 15-16 weeks of gestation. We pooled
      sera across subjects for exposure assessment, stratified on case-referent status
      and sex. Individual 1:1 matching was maintained in assembling 69 case and 69
      referent pools created from 550 case-referent pairs. Matched pools had an equal
      number of aliquots from individual women. We used an analytical strategy
      conditioning on matched set and total pool-level values of covariates to estimate
      individual-level effects. Pools of cases and referents had identical geometric
      mean bisphenol-A concentrations (0.5 ng/mL) and similar geometric standard
      deviations (2.3-2.5). Mean difference in concentration between matched pools was
      0 ng/mL, standard deviation: 1 ng/mL. Stratification by sex and control for
      confounding did not suggest bisphenol-A increased fetal growth restriction. Our
      analysis does not provide evidence to support the hypothesis that bisphenol-A
      contributes to fetal growth restriction in full-term singletons. 

PMID- 24336028
TI  - Chronic kidney disease and the aging population.

PMID- 24336027
TI  - Factors increasing vulnerability to health effects before, during and after
      floods.
AB  - Identifying the risk factors for morbidity and mortality effects pre-, during and
      post-flood may aid the appropriate targeting of flood-related adverse health
      prevention strategies. We conducted a systematic PubMed search to identify
      studies examining risk factors for health effects of precipitation-related
      floods, among Organisation for Economic Co-Operation and Development (OECD)
      member countries. Research identifying flood-related morbidity and mortality risk
      factors is limited and primarily examines demographic characteristics such as age
      and gender. During floods, females, elderly and children appear to be at greater
      risk of psychological and physical health effects, while males between 10 to 29
      years may be at greater risk of mortality. Post-flood, those over 65 years and
      males are at increased risk of physical health effects, while females appear at
      greater risk of psychological health effects. Other risk factors include previous
      flood experiences, greater flood depth or flood trauma, existing illnesses,
      medication interruption, and low education or socio-economic status. Tailoring
      messages to high-risk groups may increase their effectiveness. Target populations
      differ for morbidity and mortality effects, and differ pre-, during, and post
      flood. Additional research is required to identify the risk factors associated
      with pre- and post-flood mortality and post-flood morbidity, preferably using
      prospective cohort studies. 

PMID- 24336029
TI  - Kidney and eye diseases: common risk factors, etiological mechanisms, and
      pathways.
AB  - Chronic kidney disease is an emerging health problem worldwide. The eye shares
      striking structural, developmental, and genetic pathways with the kidney,
      suggesting that kidney disease and ocular disease may be closely linked. A
      growing number of studies have found associations of chronic kidney disease with
      age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract.
      In addition, retinal microvascular parameters have been shown to be predictive of
      chronic kidney disease. Chronic kidney disease shares common vascular risk
      factors including diabetes, hypertension, smoking, and obesity, and pathogenetic
      mechanisms including inflammation, oxidative stress, endothelial dysfunction, and
      microvascular dysfunction, with ocular diseases supporting the 'Common Soil
      Hypothesis.' In this review, we present major epidemiological evidence for these
      associations and explore underlying pathogenic mechanisms and common risk factors
      for kidney and ocular disease. Understanding the link between kidney and ocular
      disease can lead to the development of new treatment and screening strategies for
      both diseases. 

PMID- 24336030
TI  - Fructokinase activity mediates dehydration-induced renal injury.
AB  - The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy)
      has been linked with recurrent dehydration. Here we tested whether recurrent
      dehydration may cause renal injury by activation of the polyol pathway, resulting
      in the generation of endogenous fructose in the kidney that might subsequently
      induce renal injury via metabolism by fructokinase. Wild-type and fructokinase
      deficient mice were subjected to recurrent heat-induced dehydration. One group of
      each genotype was provided water throughout the day and the other group was
      hydrated at night, after the dehydration. Both groups received the same total
      hydration in 24 h. Wild-type mice that received delayed hydration developed renal
      injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular
      injury, and renal inflammation and fibrosis. This was associated with activation
      of the polyol pathway, with increased renal cortical sorbitol and fructose
      levels. Fructokinase-knockout mice with delayed hydration were protected from
      renal injury. Thus, recurrent dehydration can induce renal injury via a
      fructokinase-dependent mechanism, likely from the generation of endogenous
      fructose via the polyol pathway. Access to sufficient water during the
      dehydration period can protect mice from developing renal injury. These studies
      provide a potential mechanism for Mesoamerican nephropathy. 

PMID- 24336025
TI  - Proposed toxic and hypoxic impairment of a brainstem locus in autism.
AB  - Electrophysiological findings implicate site-specific impairment of the nucleus
      tractus solitarius (NTS) in autism. This invites hypothetical consideration of a
      large role for this small brainstem structure as the basis for seemingly
      disjointed behavioral and somatic features of autism. The NTS is the brain's
      point of entry for visceral afference, its relay for vagal reflexes, and its
      integration center for autonomic control of circulatory, immunological,
      gastrointestinal, and laryngeal function. The NTS facilitates normal
      cerebrovascular perfusion, and is the seminal point for an ascending
      noradrenergic system that modulates many complex behaviors. Microvascular
      configuration predisposes the NTS to focal hypoxia. A subregion--the "pNTS"-
      permits exposure to all blood-borne neurotoxins, including those that do not
      readily transit the blood-brain barrier. Impairment of acetylcholinesterase
      (mercury and cadmium cations, nitrates/nitrites, organophosphates, monosodium
      glutamate), competition for hemoglobin (carbon monoxide, nitrates/nitrites), and
      higher blood viscosity (net systemic oxidative stress) are suggested to
      potentiate microcirculatory insufficiency of the NTS, and thus autism.

PMID- 24336031
TI  - Personalized prophylactic anticoagulation decision analysis in patients with
      membranous nephropathy.
AB  - Primary membranous nephropathy is associated with increased risk of venous
      thromboembolic events, which are inversely correlated with serum albumin levels.
      To evaluate the potential benefit of prophylactic anticoagulation (venous
      thromboembolic events prevented) relative to the risk (major bleeds), we
      constructed a Markov decision model. The venous thromboembolic event risk
      according to serum albumin was obtained from an inception cohort of 898 patients
      with primary membranous nephropathy. Risk estimates of hemorrhage were obtained
      from a systematic literature review. Benefit-to-risk ratios were predicted
      according to bleeding risk and serum albumin. This ratio increased with worsening
      hypoalbuminemia from 4.5:1 for an albumin under 3 g/dl to 13.1:1 for an albumin
      under 2 g/dl in patients at low bleeding risk. Patients at intermediate bleeding
      risk with an albumin under 2 g/dl have a moderately favorable benefit-to-risk
      ratio (under 5:1). Patients at high bleeding risk are unlikely to benefit from
      prophylactic anticoagulation regardless of albuminemia. Probabilistic sensitivity
      analysis, to account for uncertainty in risk estimates, confirmed these trends.
      From these data, we constructed a tool to estimate the likelihood of benefit
      based on an individual's bleeding risk profile, serum albumin level, and
      acceptable benefit-to-risk ratio (www.gntools.com). This tool provides an
      approach to the decision of prophylactic anticoagulation personalized to the
      individual's needs and adaptable to dynamic changes in health status and risk
      profile. 

PMID- 24336032
TI  - Time-dependent variability in tacrolimus trough blood levels is a risk factor for
      late kidney transplant failure.
AB  - Wide variations in tacrolimus levels have been identified as a risk factor for
      inferior kidney allograft survival but past studies have not properly accounted
      for the dynamic nature of drug exposure over time. Here we evaluated whether time
      varying exposure to tacrolimus increases the risk of long-term adverse outcomes
      in a retrospective cohort study in adult kidney transplant recipients on
      tacrolimus-based immunosuppression. Time-dependent Cox proportional hazards
      models were used to examine the association between the standard deviation of
      tacrolimus levels (TacSD) starting at 1-year post-transplant and the composite
      end point of late allograft rejection, transplant glomerulopathy, or total graft
      loss (including death). Among 356 patients, there was a significant 27% increase
      in the adjusted hazard of the composite end point for every 1-unit increase in
      TacSD (hazard ratio 1.27 (95% confidence interval 1.03, 1.56)). There was also a
      graded increase in the relative hazard for the composite end point by TacSD
      threshold (hazard ratios 1.33, 1.50, 1.84, and 2.56 for TacSD 1.5, 2, 2.5, and 3,
      respectively). The results were similar for total graft loss and the composite
      end point excluding death. Thus, increased time-dependent TacSD may be an
      independent risk factor for adverse kidney transplant outcomes. TacSD may serve
      as a monitoring tool to identify high-risk patients. Whether interventions to
      decrease TacSD will improve outcomes requires further study. 

PMID- 24336033
TI  - Dialysis frequency versus dialysis time, that is the question.
AB  - We reviewed a number of prospective randomized and multiple retrospective cohort
      studies of different dialysis prescriptions: longer dialysis time, at a frequency
      of at least three times a week, or a frequency of daily hemodialysis with a
      shorter dialysis time. Interestingly, the retrospective analyses have generally
      found significant survival benefits in the intensive dialysis groups, whereas
      more modest effects were observed in the prospective randomized controlled
      trials. The reason for this discrepancy may be related to the retrospective
      nature of the studies and possible selection bias; for example, the patients who
      were prescribed more frequent dialysis may have had more difficulties with volume
      control or high blood pressure. In contrast, the randomized controlled trials of
      increased dialysis frequency, which have shown indirect and modest benefits in
      complex coprimary end points, have small sample sizes and are plagued with
      difficulties in recruitment and compliance with the randomly allocated more
      frequent dialysis. This review, which attempts to balance the potential benefits
      of more frequent dialysis with the burden on the patient's lifestyle, an
      increased risk of access malfunction, as well as societal costs of such intensive
      dialysis prescriptions, concludes in favor of the conventional three times per
      week dialysis (at a minimum) but at longer dialysis times than is currently
      prescribed based on the Kt/Vurea metric alone. 

PMID- 24336034
TI  - The cyclin-dependent kinase inhibitor p21 is essential for the beneficial effects
      of renal ischemic preconditioning on renal ischemia/reperfusion injury in mice.
AB  - The cyclin-dependent kinase inhibitor p21 plays important roles in chronic renal
      disorders; however, its roles in response to acute renal stress are unclear. Here
      we evaluated p21 in acute kidney injury and ischemic preconditioning using wild
      type and p21 knockout mice that underwent renal ischemia followed by reperfusion.
      The decline in renal function and histological changes were worse in the knockout
      than in wild-type mice. Ischemia/reperfusion increased p21 expression in the
      kidney of wild-type mice compared with sham surgery, suggesting p21 may confer
      tolerance to ischemia/reperfusion injury. We next tested whether p21 is
      associated with the protective effect of ischemic preconditioning, an established
      method to reduce ischemia/reperfusion injury. Ischemic preconditioning attenuated
      ischemia/reperfusion injury in wild-type but not p21-knockout mice. This
      preconditioning decreased the number of proliferating tubular cells before but
      increased them at 24 h after ischemia/reperfusion in the kidneys of wild-type
      mice. In p21-knockout mice, ischemic preconditioning did not change the number of
      proliferating cells before but decreased them after ischemia/reperfusion.
      Ischemic preconditioning increased renal p21 expression and the number of cells
      in the G1 phase of the cell cycle before ischemia/reperfusion compared with sham
      surgery. Thus, renal p21 is essential for the beneficial effects of renal
      ischemic preconditioning. Transient cell cycle arrest induced by ischemic
      preconditioning by a p21-dependent pathway seems to be important for subsequent
      tubular cell proliferation after ischemia/reperfusion. 

PMID- 24336035
TI  - Can puncture increase the risk of intra-articular adhesion in the
      temporomandibular joint?
AB  - PURPOSE: This study aims to compare the incidence and severity of intra-articular
      adhesion under arthroscopy between patients with and without a history of joint
      puncture. PATIENTS AND METHODS: Eighty-nine patients with internal derangements
      of TMJ who underwent arthroscopic disc repositioning and suturing surgery from
      February 2008 to September 2008 were included in this study. Patients were
      divided into 2 groups based on whether the patient had undergone joint puncture
      before surgery or not. The diagnosis of intra-articular adhesion was made
      according to the manifestation under arthroscopy. Incidence and severity of intra
      articular adhesion between these 2 groups was compared. RESULTS: The incidence of
      intra-articular adhesion in the patients with a history of puncture was 69.23%,
      which was higher than that in the patients without a history of puncture
      (24.36%). The difference was statistically significant (P < 0.05). The incidence
      of severe adhesions in patients with a history of joint puncture was also higher
      than that in patients without a history of puncture (26.09% vs. 2.56%, P < 0.01).
      CONCLUSIONS: Puncture may increase the risk of intra-articular adhesion in
      patients with internal derangement.

PMID- 24336036
TI  - A digital interactive human brain atlas based on Chinese visible human datasets
      for anatomy teaching.
AB  - As we know, the human brain is one of the most complicated organs in the human
      body, which is the key and difficult point in neuroanatomy and sectional anatomy
      teaching. With the rapid development and extensive application of imaging
      technology in clinical diagnosis, doctors are facing higher and higher
      requirement on their anatomy knowledge. Thus, to cultivate medical students to
      meet the needs of medical development today and to improve their ability to read
      and understand radiographic images have become urgent challenges for the medical
      teachers. In this context, we developed a digital interactive human brain atlas
      based on the Chinese visible human datasets for anatomy teaching (available for
      free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas
      simultaneously provides views in all 3 primary planes of section. The main
      structures of the human brain have been anatomically labeled in all 3 views. It
      is potentially useful for anatomy browsing, user self-testing, and automatic
      student assessment. In a word, it is interactive, 3D, user friendly, and free of
      charge, which can provide a new, intuitive means for anatomy teaching. 

PMID- 24336037
TI  - Ischemic optic neuropathy after carotid body tumor resection.
AB  - Incidence estimates for postoperative vision loss after nonocular surgery range
      from 0.013% for all surgeries up to 0.2% following spine surgery. The most common
      neuro-ophthalmologic causes of postoperative vision loss are the ischemic optic
      neuropathies (IONs), either anterior or posterior.This complication of case
      reports suggests that a combination of prolonged surgery in the prone position,
      decreased ocular perfusion pressure, blood loss and anemia/hemodilution, and
      infusion of large quantities of intravenous fluids are some of the potential
      factors involved in the etiology of postoperative ION. The specific pathogenesis
      and risk factors underlying these neuro-ophthalmic complications remain unknown,
      and physicians should be alert to the potential for loss of vision in the
      postoperative period. We report the only cases of ION after carotid body tumor
      resection in the literature and review current theories regarding the etiology
      and diagnosis of vision loss. 

PMID- 24336038
TI  - Current techniques and protocols in the surgical management of scaphocephaly in
      young infants.
AB  - BACKGROUND: Many techniques and protocols are currently used in the treatment of
      scaphocephaly worldwide, including total calvarial remodeling and minimally
      invasive strip craniectomies. This study reviews current techniques and protocols
      used in young infants (aged <= 6 months) as well as the outcomes in terms of
      reoperation rates. METHODS: A short questionnaire was designed including
      questions about the preferred surgical techniques, transfusion protocols, and
      reoperation rates. Surgeons from the International Society of Craniofacial
      Surgery and the International Society for Pediatric Neurosurgery were requested
      to respond to this questionnaire online or by e-mail. Responses during a 2-week
      period were collated and analyzed using Fisher exact test. RESULTS: A total of 91
      surgeons responded from the craniofacial centers around the world, of which 93.4%
      completed the questionnaire. Most respondents were from North America and Europe
      (35% and 20%, respectively). The operative volume was less than 15 cases per year
      in 56%, and the bicoronal skin incision was most commonly used (81%).
      Postoperative drainage was not performed by 55% but was statistically more common
      with use of the bicoronal incision (P = 0.029). Of the respondents, 66% used
      calvarial remodeling, and 34% strip craniectomy. Blood was most commonly
      transfused at a hemoglobin level under 8 g/dL (31%), with a mean transfusion rate
      of 66%. Of the respondents, 44% transfused in more than 90% of the cases, whereas
      only 18% transfused in 20% or less of the cases. The mean reoperation rate for
      secondary fusion was 1.7%, and 41% of the respondents claimed a 0% reoperation
      rate. A statistically higher frequency of reoperation was reported by centers
      with a case load of more than 15 cases per year (P = 0.035), and no statistical
      correlation was found with the type of surgical technique. CONCLUSIONS: Our
      survey of neurosurgeons and craniofacial plastic surgeons worldwide shows that
      for young infants treated for scaphocephaly, the bicoronal incision is most
      commonly used and a greater number of surgeons do not use drains. A great
      variability in the transfusion protocols used in the care of these patients as
      well as a low reoperation rate were also found. The latter however may suggest a
      lack of strict monitoring in most centers. Overall, this study presents a
      snapshot of the current surgical treatment of this subset of patients and should
      serve as a basis for quality improvement and outcome monitoring in their surgical
      management.

PMID- 24336039
TI  - Complete reduction with traction of the infraorbital neurovascular bundle in a
      delayed patient with white-eyed blow-out fracture.
AB  - In case of delayed surgery, if an orbital floor fracture involves the
      infraorbital canal, adhesions may form between the infraorbital neurovascular
      bundle and herniated muscle, and manipulations to reduce the fracture may lead to
      unexpected bleeding due to injury of the infraorbital artery. The author reports
      a case of a white-eyed blow-out fracture patient, who visited our clinic one-and
      a-half months after the injury. Exploration of the fracture confirmed intensive
      fibrosis of the infraorbital neurovascular bundle and the entrapped inferior
      rectus muscle at the fracture site. The author was able to reduce the muscle
      completely with the release of the fibrotic tissue around the nerve bundle by
      using a vessel loop to safely retract the neurovascular bundle upwards, and
      obtained good results. 

PMID- 24336040
TI  - Posttraumatic cavernous hemangioma of the skull.
AB  - A 59-year-old man presented with a slowly enlarging mass in the lateral orbital
      rim of the left eye for 1 year. He also reported a history of crania defect in
      the left front bone (6 years earlier) which was confirmed on the former computed
      tomographic (CT) scan. On examination, the solid mass lesion located in the left
      frontal extends to the lateral orbital rim of the left eye. CT scan showed a mass
      with poorly defined margins, which invaded the neighboring tissue and nearly
      damaged the bone, and located on the exact site of the preceding crania defect.
      Complete resection was performed, and the clinical diagnosis of cavernous
      hemangioma was confirmed on histopathologic examination. Skull cavernous
      hemangiomas are rare tumors for which the origin is not yet clear. We report a
      case in which the intraosseous hemangiomas developed at the same site of the
      preceding crania defect.

PMID- 24336041
TI  - Rehabilitation of the maxillary arch after bone graft using immediate loading
      with implant-supported fixed restoration.
AB  - Moderate and controlled loading environments support or enhance osteogenesis,
      and, consequently, a high degree of bone-to-implant contact can be acquired. This
      is because when osteoprogenitor cells are exposed to limited physical
      deformation, their differentiation into osteoblasts is enhanced. Then, some range
      of microstrain is considered advantageous for bone ingrowth and osseointegration.
      The primary stability has been considered one of the main clinical means of
      controlling micromotion between the implant and the forming interfacial tissue,
      which helps to establish the proper mechanical environment for osteogenesis.
      Based on the biological aspects of immediate loading (IL), the objective of this
      study is to present a clinical case of maxillary arch rehabilitation using
      immediate loading with implant-supported fixed restoration after bone graft. Ten
      dental implants were placed in the maxilla 6 months after the autogenous bone
      graft, removed from the mandible (bilateral oblique line and chin), followed by
      the installation of an immediate-load fixed cross-arch implant-supported
      restoration because primary stability was reached for 8 implants. In addition,
      instructions about masticatory function and how it is related to interfacial
      micromotion were addressed and emphasized to the patient. The reasons for the IL
      were further avoidance of an interim healing phase, a potential reduction in the
      number of clinical interventions for the patient, and aesthetic reasons. After
      monitoring the rehabilitation for 8 years, the authors can conclude that
      maxillary IL can be performed followed by a well-established treatment planning
      based on computed tomography, providing immediate esthetics and function to the
      patient even when autogenous bone graft was previously performed in the maxilla. 

PMID- 24336042
TI  - Simultaneous chin onlay bone graft using elongated coronoid in the treatment of
      temporomandibular joint ankylosis.
AB  - Temporomandibular joint (TMJ) ankylosis is a disabling condition that causes
      problems in mastication, digestion, speech, appearance, and hygiene. Treatment
      goals are to restore the joint function, to improve facial appearance, and to
      reestablish harmony among them. To achieve these goals, various strategies have
      been reported as 1-stage or multistage protocols. We describe a novel method to
      augment the chin structure with elongated coronoid process of the mandible, which
      is a sequence of TMJ ankylosis. By this 1-stage treatment that includes gap
      arthroplasty with interpositional temporalis fascia graft and chin augmentation
      with autogenous bone graft (elongated coronoid), functional disability and facial
      deformity of the patient with TMJ ankylosis were improved simultaneously. 

PMID- 24336043
TI  - Reconstruction of extensive through-and-through cheek defects with free
      anterolateral thigh flap.
AB  - OBJECTIVE: The purpose of this study was to assess the clinical features and
      therapeutic efficacy of extensive through-and-through cheek defects
      reconstruction with free anterolateral thigh flap. METHODS: A total of 11
      patients underwent simultaneous tumor radical resection and through-and-through
      cheek defects reconstruction with free anterolateral thigh flap. RESULTS: In
      these 11 patients, 7 patients had undergone the reconstruction of through-and
      through cheek defects with the folded anterolateral thigh flap (2 skin islands
      and an intervening de-epithelialized zone); 4 patients had undergone the
      reconstruction of through-and-through cheek defects with the 2 separate skin
      paddles anterolateral thigh flap in 1 single pedicle. All of these 11 flaps were
      free fasciocutaneous anterolateral thigh flaps. The subcutaneous fat thickness of
      the anterolateral thigh flap is less than 1.5 cm. CONCLUSIONS: The free
      anterolateral thigh flap was one of the versatile soft tissue flaps in the
      extensive through-and-through cheek defects reconstruction.

PMID- 24336044
TI  - Mean platelet volume levels in children with adenoid hypertrophy.
AB  - Adenoid hypertrophy (AH) is a common disorder in children, resulting in chronic
      nasal congestion. This chronic congestion should be evaluated carefully because
      it can lead to chronic upper airway obstruction. Many authors have suggested that
      increased nasal resistance to respiration may cause disturbances in the pulmonary
      ventilation and carry the risk of cardiopulmonary diseases. Mean platelet volume
      (MPV) is a marker of platelet function and is positively associated with
      indicators of platelet activity. Mean platelet volume is an indicator of larger
      and more reactive platelets and has been shown to be increased in patients with
      vascular disease, including peripheral, pulmonary, and coronary artery disease.
      Recently, MPV levels have also been shown to be increased in patients with severe
      obstructive sleep apnea, and marked nasal septal deviation. Moreover, increased
      MPV has also been shown to have a prognostic role in cardiovascular disease. We
      investigated whether MPV is higher in patients with AH and whether higher MPV
      levels can be reduced by adenoidectomy. To the best of our knowledge, this is the
      first study to investigate MPV in patients with AH. Our results suggest that MPV,
      a determinant of platelet activation, is elevated in patients with AH and
      adenoidectomy is an effective therapeutic measure in such patients. Increased
      platelet activation may be related to an increase of cardiopulmonary risk in
      patients with AH. 

PMID- 24336046
TI  - Rehabilitation approaches to dysphagia that was developed for a patient who
      attempted to commit suicide by hanging: a case report.
AB  - We report our experience with a case of attempted suicidal hanging presenting
      with dysphagia, in which rehabilitation approaches resulted in improvement. A 36
      year-old man was discovered collapsed at home. From the finding of a broken cord
      nearby, attempted suicide by hanging was suspected. He was transported to
      hospital after 40 minutes, and regained consciousness after emergency treatment.
      There were no noteworthy findings on brain magnetic resonance imaging, cervical
      spine computed tomography, or vocal cord examination. There were no noteworthy
      psychiatric disorders or cognitive abnormalities. On hospital day 10, he showed
      signs of dysphagia. Videofluoroscopic examination of swallowing revealed piriform
      sinuses residue and aspiration after ingestion of jelly in any posture.
      Rehabilitation approaches were started based on the diagnosis of dysphagia due to
      impaired transit through the piriform sinuses. The patient achieved independent
      oral intake by 40 days after the injury. In this case, dysphagia was considered
      attributable to compression of the vagus nerves running along the lateral aspects
      of the neck by the cord used in the hanging. If compression is brief, full
      functional recovery can be expected. Implementation of rehabilitation approaches
      is also important in this situation. 

PMID- 24336047
TI  - Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling
      regulates abnormal epithelial cell proliferation.
AB  - Calcium deficiency causes abnormal colonic growth and increases colon cancer risk
      with poorly understood mechanisms. Here we elucidate a novel signaling mechanism
      underlying the Ca(2+) deficiency-induced epithelial proliferation using a unique
      animal model. The zebrafish larval yolk sac skin contains a group of Ca(2+)
      transporting epithelial cells known as ionocytes. Their number and density
      increases dramatically when acclimated to low [Ca(2+)] environments. BrdU pulse
      labeling experiments suggest that low [Ca(2+)] stimulates pre-existing ionocytes
      to re-enter the cell cycle. Low [Ca(2+)] treatment results in a robust and
      sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively.
      These ionocytes specifically express Igfbp5a, a high-affinity and specific
      binding protein for insulin-like growth factors (IGFs) and the Ca(2+)-selective
      channel Trpv5/6. Inhibition or knockdown of Igfbp5a, IGF1 receptor, PI3K, and Akt
      attenuates low [Ca(2+)]-induced ionocyte proliferation. The role of Trpv5/6 was
      investigated using a genetic mutant, targeted knockdown, and pharmacological
      inhibition. Loss-of-Trpv5/6 function or expression results in elevated pAkt
      levels and increased ionocyte proliferation under normal [Ca(2+)]. These
      increases are eliminated in the presence of an IGF1R inhibitor, suggesting that
      Trpv5/6 represses IGF1R-PI3K-Akt signaling under normal [Ca(2+)]. Intriguingly,
      blockade of Trpv5/6 activity inhibits the low [Ca(2+)]-induced activation of Akt.
      Mechanistic analyses reveal that the low [Ca(2+)]-induced IGF signaling is
      mediated through Trpv5/6-associated membrane depolarization. Low extracellular
      [Ca(2+)] results in a similar amplification of IGF-induced PI3K-PDK1-Akt
      signaling in human colon cancer cells in a TRPV6-dependent manner. These results
      uncover a novel and evolutionarily conserved signaling mechanism that contributes
      to the abnormal epithelial proliferation associated with Ca(2+) deficiency. 

PMID- 24336049
TI  - Retraction: INrf2 (Keap1) targets Bcl-2 degradation and controls cellular
      apoptosis.

PMID- 24336048
TI  - Microglia convert aggregated amyloid-beta into neurotoxic forms through the
      shedding of microvesicles.
AB  - Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta)
      deposition, which activates microglia, induces neuroinflammation and drives
      neurodegeneration. Recent evidence indicates that soluble pre-fibrillar Abeta
      species, rather than insoluble fibrils, are the most toxic forms of Abeta.
      Preventing soluble Abeta formation represents, therefore, a major goal in AD. We
      investigated whether microvesicles (MVs) released extracellularly by reactive
      microglia may contribute to AD degeneration. We found that production of myeloid
      MVs, likely of microglial origin, is strikingly high in AD patients and in
      subjects with mild cognitive impairment and that AD MVs are toxic for cultured
      neurons. The mechanism responsible for MV neurotoxicity was defined in vitro
      using MVs produced by primary microglia. We demonstrated that neurotoxicity of
      MVs results from (i) the capability of MV lipids to promote formation of soluble
      Abeta species from extracellular insoluble aggregates and (ii) from the presence
      of neurotoxic Abeta forms trafficked to MVs after Abeta internalization into
      microglia. MV neurotoxicity was neutralized by the Abeta-interacting protein PrP
      and anti-Abeta antibodies, which prevented binding to neurons of neurotoxic
      soluble Abeta species. This study identifies microglia-derived MVs as a novel
      mechanism by which microglia participate in AD degeneration, and suggest new
      therapeutic strategies for the treatment of the disease. 

PMID- 24336050
TI  - Suppression of PPARgamma through MKRN1-mediated ubiquitination and degradation
      prevents adipocyte differentiation.
AB  - The central regulator of adipogenesis, PPARgamma, is a nuclear receptor that is
      linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3
      ligase of PPARgamma that induces its ubiquitination, followed by proteasome
      dependent degradation. Furthermore, we identified two lysine sites at 184 and 185
      that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of
      MKRN1 reduced PPARgamma protein levels and suppressed adipocyte differentiation
      in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte
      differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased
      capacity for adipocyte differentiation compared with wild-type MEFs, with a
      concomitant increase of PPARgamma and adipogenic markers. Together, these data
      indicate that MKRN1 is an elusive PPARgamma E3 ligase that targets PPARgamma for
      proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1
      as a novel target for diseases involving PPARgamma. 

PMID- 24336052
TI  - Why do we need a systematic review of pneumococcal conjugate vaccine dosing
      schedules?

PMID- 24336051
TI  - A failure in energy metabolism and antioxidant uptake precede symptoms of
      Huntington's disease in mice.
AB  - Huntington's disease has been associated with a failure in energy metabolism and
      oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in
      the brain where it acts as a messenger, modulating neuronal metabolism. Using an
      electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic
      acid flux from astrocytes to neurons, which is responsible for alterations in
      neuronal metabolic substrate preferences. Here using striatal neurons derived
      from knock-in mice expressing mutant huntingtin (STHdhQ cells), we study ascorbic
      acid transport. When extracellular ascorbic acid concentration increases, as
      occurs during synaptic activity, ascorbic acid transporter 2 (SVCT2) translocates
      to the plasma membrane, ensuring optimal ascorbic acid uptake for neurons. In
      contrast, SVCT2 from cells that mimic HD symptoms (dubbed HD cells) fails to
      reach the plasma membrane under the same conditions. We reason that an early
      impairment of ascorbic acid uptake in HD neurons could lead to early metabolic
      failure promoting neuronal death. 

PMID- 24336053
TI  - Systematic review of the effect of pneumococcal conjugate vaccine dosing
      schedules on vaccine-type invasive pneumococcal disease among young children.
AB  - BACKGROUND: Pneumococcal conjugate vaccines (PCV) are being implemented globally
      using a variety of different schedules. The optimal schedule to maximize
      protection of vaccinated children against vaccine-type invasive pneumococcal
      disease (VT-IPD) is not known. METHODS: To assess the relative benefit of various
      PCV dosing schedules, we conducted a systematic review of studies published in
      English from 1994 to 2010 (supplemented post hoc with studies from 2011) on PCV
      effectiveness against VT-IPD among children targeted to receive vaccine. Data on
      2-dose and 3-dose primary series, both with and without a booster ("2+0," "2+1,"
      "3+0" and "3+1"), were included. For observational studies using surveillance
      data or case counts, we calculated percentage reduction in VT-IPD before and
      after PCV introduction. RESULTS: Of 4 randomized controlled trials and 31
      observational studies reporting VT-IPD among young children, none evaluated a 2+0
      complete series, 7 (19%) evaluated 2+1, 4 (11%) 3+0 and 27 (75%) 3+1. Most (86%)
      studies were from North America or Europe. Only 1 study (observational) directly
      compared 2 schedules (3+0 vs. 3+1); results supported the use of a booster dose.
      In clinical trials, vaccine efficacy ranged from 65% to 71% with 3+0 and 83% to
      94% with 3+1. Surveillance data and case counts demonstrate reductions in VT-IPD
      of up to 100% with 2+1 (6 studies) or 3+1 (17 studies) schedules and up to 90%
      with 3+0 (2 studies). Reductions were observed as early as 1 year after PCV
      introduction. CONCLUSIONS: These data support the use of 2+1, 3+0 and 3+1
      schedules, although most data of PCV impact on VT-IPD among young children are
      from high-income countries using 3+1. Differences between schedules for impact on
      VT-IPD are difficult to discern based on available data.

PMID- 24336054
TI  - Systematic review of the effect of pneumococcal conjugate vaccine dosing
      schedules on immunogenicity.
AB  - BACKGROUND: Despite the breadth of studies demonstrating benefits of pneumococcal
      conjugate vaccine (PCV), uncertainty remains regarding the optimal PCV dosing
      schedule in infants. METHODS: We conducted a systematic literature review of PCV
      immunogenicity published from 1994 to 2010 (supplemented post hoc with studies
      from 2011). Studies included for analysis evaluated >=2 doses of 7-valent or
      higher product (excluding Aventis-Pasteur PCV11) administered to nonhigh-risk
      infants <=6 months of age. Impact of PCV schedule on geometric mean antibody
      concentration (GMC) and proportion of subjects over 0.35 mcg/mL were assessed at
      various time points; the GMC 1 month postdose 3 (for various dosing regimens) for
      serotypes 1, 5, 6B, 14, 19F and 23F was assessed in detail using random effects
      linear regression, adjusted for product, acellular diphtheria-tetanus
      pertussis/whole-cell diphtheria- tetanus-pertussis coadministration, laboratory
      method, age at first dose and geographic region. RESULTS: From 61 studies, we
      evaluated 13 two-dose (2+0) and 65 three-dose primary schedules (3+0) without a
      booster dose, 11 "2+1" (2 primary plus booster) and 42 "3+1" schedules. The GMC
      after the primary series was higher following 3-dose schedules compared with 2
      dose schedules for all serotypes except for serotype 1. Pre- and postbooster GMCs
      were generally similar regardless of whether 2 or 3 primary doses were given.
      GMCs were significantly higher for all serotypes when dose 3 was administered in
      the second year (2+1) compared with <=6 months of age (3+0). CONCLUSIONS: While
      giving the third dose in the second year of life produces a higher antibody
      response than when given as part of the primary series in the first 6 months, the
      lower GMC between the 2-dose primary series and booster may result in less
      disease protection for infants in that interval than those who completed the 3
      dose primary series. Theoretical advantages of higher antibodies induced by
      giving the third dose in the second year of life, such as increased protection
      against serotype 1 disease, longer duration of protection or more rapid induction
      of herd effects, need to be evaluated in practice.

PMID- 24336055
TI  - The differential impact of coadministered vaccines, geographic region, vaccine
      product and other covariates on pneumococcal conjugate vaccine immunogenicity.
AB  - BACKGROUND: Antipneumococcal capsular polysaccharide antibody concentrations are
      used as predictors of vaccine efficacy against vaccine serotype (ST) pneumococcal
      disease among infants. While pneumococcal conjugate vaccines (PCV) are
      recommended globally, factors associated with optimal PCV immune response are not
      well described. We aimed to systematically assess local setting factors, beyond
      dosing schedule, which may affect PCV antibody levels. METHODS: We conducted a
      literature review of PCV immunogenicity, abstracting data from published reports,
      unpublished sources, and conference abstracts from 1994 to 2010 (and ad hoc 2011
      reports). Studies included in this analysis evaluated >= 2 primary doses of PCV
      before 6 months of age in non-high-risk populations, used 7-valent or higher PCV
      products (excluding Aventis-Pasteur and Merck products) and provided information
      on geometric mean concentration (GMC) for STs 1, 5, 6B, 14, 19F or 23F. Using
      random effects meta-regression, we assessed the impact of geographic region,
      coadministered vaccines and PCV product on postprimary GMC, adjusting for dosing
      schedule and ELISA laboratory method. RESULTS: Of 12,980 citations reviewed, we
      identified 103 vaccine study arms for this analysis. Children in studies from
      Asia, Africa and Latin America had significantly higher GMC responses compared
      with those in studies from Europe and North America. Coadministration with
      acellular pertussis DTP compared with whole-cell DTP had no effect on PCV
      immunogenicity except for ST14, where GMCs were higher when coadministered with
      acellular pertussis DTP. Vaccine product, number of PCV doses, dosing interval,
      age at first dose and ELISA laboratory method also affected the GMC. CONCLUSIONS:
      PCV immunogenicity is associated with geographic region and vaccine product;
      however, the associations and magnitude varied by ST. Consideration of these
      factors is essential when comparing PCV immunogenicity results between groups and
      should be included in the evidence base when selecting optimal PCV vaccine
      schedules in specific settings.

PMID- 24336056
TI  - Systematic review of the effect of pneumococcal conjugate vaccine dosing
      schedules on prevention of pneumonia.
AB  - BACKGROUND: Pneumonia is the leading cause of morbidity and mortality among
      children <5 years of age globally. Pneumococcal conjugate vaccines (PCVs) are
      known to provide protection against vaccine serotype pneumococcal pneumonia;
      uncertainty exists regarding the optimum PCV dosing schedule. METHODS: We
      conducted a systematic review of studies published from 1994 to 2010
      (supplemented post hoc with studies from 2011) documenting the effect of PCV
      dosing schedules on clinical and radiologically confirmed pneumonia, pneumococcal
      pneumonia and empyema among children of ages targeted to receive vaccine. Data on
      2- and 3-dose schedules were included. Percent change of pneumonia incidence
      rates from baseline to most recent year post-PCV introduction was calculated.
      RESULTS: We identified 42 primary citations that evaluated PCV schedules and
      pneumonia. Thirty-seven (88%) were from North America, Europe or Australia; 37
      (88%) evaluated PCV7 and 1 (2%) PCV10. Two studies (both observational) compared
      multiple schedules within the study. We found evidence of reduced clinical and
      radiologically confirmed pneumonia incidence for all schedules, including 2+1 (1
      nonrandomized trial, 5 observational studies), 3+0 (5 randomized trials, 2
      observational studies) and 3+1 (5 clinical trials, 24 observational studies)
      schedules. The magnitude of disease impact did not differ among schedules.
      Evidence for impact on pneumococcal pneumonia and empyema varied. CONCLUSIONS:
      All schedules (2+1, 3+0 and 3+1) reduced clinical and radiologically confirmed
      pneumonia. Quantifying differences in pneumonia disease impact between schedules
      was difficult due to heterogeneity among studies in design, case definition and
      population. These findings support World Health Organization recommendations for
      3-dose schedules administered as either 3+0 or 2+1 regimens. Pneumonia impact
      data are still needed on expanded serotype PCV products, developing country
      settings and the role for a booster dose.

PMID- 24336057
TI  - Systematic review of the effect of pneumococcal conjugate vaccine dosing
      schedules on vaccine-type nasopharyngeal carriage.
AB  - BACKGROUND: Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage
      of vaccine type (VT) pneumococci, an important driver of vaccine programs'
      overall benefits. The dosing schedule that best reduces carriage is unclear.
      METHODS: We performed a systematic review of English language publications from
      1994 to 2010 (supplemented post hoc with studies from 2011) reporting PCV effects
      on VT carriage to assess variability in effect by dosing schedule. RESULTS: We
      identified 32 relevant studies (36 citations) from 12,980 citations reviewed.
      Twenty-one (66%) evaluated PCV7; none used PCV10 or PCV13. Five studies evaluated
      2 primary doses and 13 three primary doses. After the first year of life, 14
      evaluated 3-dose primary series with PCV booster (3+1), seven 3 doses plus 23
      valent polysaccharide booster "3+1PPV23," five "3+0," four "2+1," three
      "2+1PPV23" and two "2+0." Four studies directly compared schedules. From these, 3
      primary doses reduced VT carriage more than 2 doses at 1-7 months following the
      series (1 study significant; 2 borderline). In a study, the 2+1 schedule reduced
      VT carriage more than 2+0 at 18, but not at 24 months of age. One study of a 23
      valent pneumococcal polysaccharide vaccine booster showed no effect. All 16
      clinical trials with unvaccinated controls and 11 observational studies with
      before-after designs showed reduction in VT carriage. CONCLUSIONS: The available
      literature demonstrates VT-carriage reduction for 2+0, 2+1, 3+0 and 3+1 PCV
      schedules, but not for 23-valent pneumococcal polysaccharide vaccine booster.
      Comparisons between schedules show that 3 primary doses and a 2+1 schedule may
      reduce carriage more than 2 primary doses and a 2+0 schedule, respectively.

PMID- 24336058
TI  - Systematic review of the indirect effect of pneumococcal conjugate vaccine dosing
      schedules on pneumococcal disease and colonization.
AB  - BACKGROUND: To aid decision making for pneumococcal conjugate vaccine (PCV) use
      in infant national immunization programs, we summarized the indirect effects of
      PCV on clinical outcomes among nontargeted age groups. METHODS: We systematically
      reviewed the English literature on infant PCV dosing schedules published from
      1994 to 2010 (with ad hoc addition of 2011 articles) for outcomes on children >5
      years of age and adults including vaccine-type nasopharyngeal carriage (VT-NP),
      vaccine-type invasive pneumococcal disease (VT-IPD) and syndromic pneumonia.
      RESULTS: Of 12,980 citations reviewed, we identified 21 VT-IPD, 6 VT-NP and 9
      pneumonia studies. Of these 36, 21 (58%) included 3 primary doses plus PCV or
      pneumococcal polysaccharide vaccine (PPV23) booster schedule (3+1 or 3+PPV23), 5
      (14%) 3+0, 9 (25%) 2+1 and 1 (3%) 2+0. Most (95%) were PCV7 studies. Among
      observational VT-IPD studies, all schedules (2+1, 3+0 and 3+1) demonstrated
      reductions in incidence among young adult groups. Among syndromic pneumonia
      observational studies (2+1, 3+0 and 3+1), only 3+1 schedules showed significant
      indirect impact. Of 2 VT-NP controlled trials (3+0 and 3+1) and 3 VT-NP
      observational studies (2+1, 3+1 and 3+PPV23), 3+1 and 3+PPV23 schedules showed
      significant indirect effect. The 1 study to directly compare between schedules
      was a VT-NP study (2+0 vs. 2+1), which found no indirect effect on older siblings
      and parents of vaccinated children with either schedule. CONCLUSIONS: Indirect
      benefit of a 3+1 infant PCV dosing schedule has been demonstrated for VT-IPD, VT
      NP and syndromic pneumonia; 2+1 and 3+0 schedules have demonstrated indirect
      effect only for VT-IPD. The choice of optimal infant PCV schedule is limited by
      data paucity on indirect effects, especially a lack of head-to-head studies and
      studies of PCV10 and PCV13.

PMID- 24336059
TI  - Dosing schedules for pneumococcal conjugate vaccine: considerations for policy
      makers.
AB  - Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and
      13 serotypes became available in 2010, the number of national policy makers
      considering these vaccines has steadily increased. An important consideration for
      a national immunization program is the timing and number of doses-the schedule
      that will best prevent disease in the population. Data on disease epidemiology
      and the efficacy or effectiveness of PCV schedules are typically considered when
      choosing a schedule. Practical concerns, such as the existing vaccine schedule,
      and vaccine program performance are also important. In low-income countries,
      pneumococcal disease and deaths typically peak well before the end of the first
      year of life, making a schedule that provides PCV doses early in life (eg, a 6-,
      10- and 14-week schedule) potentially the best option. In other settings, a
      schedule including a booster dose may address disease that peaks in the second
      year of life or may be seen to enhance a schedule already in place. A large and
      growing body of evidence from immunogenicity studies, as well as clinical trials
      and observational studies of carriage, pneumonia and invasive disease, has been
      systematically reviewed; these data indicate that schedules of 3 or 4 doses all
      work well, and that the differences between these regimens are subtle, especially
      in a mature program in which coverage is high and indirect (herd) effects help
      enhance protection provided directly by a vaccine schedule. The recent World
      Health Organization policy statement on PCVs endorsed a schedule of 3 primary
      doses without a booster or, as a new alternative, 2 primary doses with a booster
      dose. While 1 schedule may be preferred in a particular setting based on local
      epidemiology or practical considerations, achieving high coverage with 3 doses is
      likely more important than the specific timing of doses. 

PMID- 24336060
TI  - Methods for a systematic review of pneumococcal conjugate vaccine dosing
      schedules.
AB  - BACKGROUND: Streptococcus pneumoniae causes a considerable amount of morbidity
      and mortality in children <5. However, pneumococcal conjugate vaccines (PCVs) can
      prevent much of this burden. Until recently, PCVs were mostly available only in
      developed countries using a variety of dosing schedules. As more lower income
      countries make decisions to introduce PCV into their national immunization
      programs, an optimal schedule with which to administer PCV has become a key
      policy question. METHODS: We performed a systematic review of English literature
      published from 1994 to 2010 on the effects of PCV dosing schedules on
      immunogenicity, nasopharyngeal carriage, invasive pneumococcal disease and
      pneumonia. Data were independently double abstracted and cleaned for analysis.
      Descriptive analyses were performed. RESULTS: We identified 12,980 citations from
      the literature search (12,976) and secondary means (44). Double review of titles
      and abstracts yielded 769 articles that underwent full data abstraction. Of
      these, 350 were further analyzed and are presented in separate reports in this
      supplement. CONCLUSIONS: This article presents the methods utilized in our
      systematic review. Because of the heterogenity of the study methods of the
      reports identified by this review, we did not conduct formal meta-analyses.
      However, these methods allow us to present a full landscape of the literature on
      PCV dosing schedules.

PMID- 24336061
TI  - Xylitol affects the intestinal microbiota and metabolism of daidzein in adult
      male mice.
AB  - This study examined the effects of xylitol on mouse intestinal microbiota and
      urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a
      food additive. The intestinal microbiota seems to play an important role in
      isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We
      hypothesized that dietary xylitol changes intestinal microbiota and, therefore,
      the metabolism of isoflavonoids in mice. Male mice were randomly divided into two
      groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed
      a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total
      cholesterol concentrations were significantly lower in the XD group than in the
      CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD
      group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight)
      were significantly greater in the XD group than in the CD group (p < 0.01). The
      cecal microbiota differed between the two dietary groups. The occupation ratios
      of Bacteroides were significantly greater in the CD than in the XD group (p <
      0.05). This study suggests that xylitol has the potential to affect the
      metabolism of daidzein by altering the metabolic activity of the intestinal
      microbiota and/or gut environment. Given that equol affects bone health, dietary
      xylitol plus isoflavonoids may exert a favorable effect on bone health.

PMID- 24336062
TI  - Antioxidant enzymatic activities and gene expression associated with heat
      tolerance in the stems and roots of two cucurbit species ("Cucurbita maxima" and
      "Cucurbita moschata") and their interspecific inbred line "Maxchata".
AB  - The elucidation of heat tolerance mechanisms is required to combat the challenges
      of global warming. This study aimed to determine the antioxidant enzyme responses
      to heat stress, at the enzymatic activity and gene expression levels, and to
      investigate the antioxidative alterations associated with heat tolerance in the
      stems and roots of squashes using three genotypes differing in heat tolerance.
      Plants of heat-tolerant "C. moschata", thermolabile "C. maxima" and moderately
      heat-tolerant interspecific inbred line "Maxchata" genotypes were exposed to
      moderate (37  degrees C) and severe (42  degrees C) heat shocks. "C. moschata"
      exhibited comparatively little oxidative damage, with the lowest hydrogen
      peroxide (H2O2), superoxide (O2(-)) and malondialdehyde (MDA) contents in the
      roots compared to stems, followed by "Maxchata". The enzyme activities of
      superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and
      peroxidase (POD) were found to be increased with heat stress in tolerant
      genotypes. The significant inductions of FeSOD, MnSOD, APX2, CAT1 and CAT3
      isoforms in tolerant genotypes suggested their participation in heat tolerance.
      The differential isoform patterns of SOD, APX and CAT between stems and roots
      also indicated their tissue specificity. Furthermore, despite the sequence
      similarity of the studied antioxidant genes among "C. maxima" and "Maxchata",
      most of these genes were highly induced under heat stress in "Maxchata", which
      contributed to its heat tolerance. This phenomenon also indicated the involvement
      of other unknown genetic and/or epigenetic factors in controlling the expression
      of these antioxidant genes in squashes, which demands further exploration.

PMID- 24336063
TI  - Hypoxia-induced collagen synthesis of human lung fibroblasts by activating the
      angiotensin system.
AB  - The exact molecular mechanism that mediates hypoxia-induced pulmonary fibrosis
      needs to be further clarified. The aim of this study was to explore the effect
      and underlying mechanism of angiotensin II (Ang II) on collagen synthesis in
      hypoxic human lung fibroblast (HLF) cells. The HLF-1 cell line was used for in
      vitro studies. Angiotensinogen (AGT), angiotensin converting enzyme (ACE),
      angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R)
      expression levels in human lung fibroblasts were analysed using real-time
      polymerase chain reaction (RT-PCR) after hypoxic treatment. Additionally, the
      collagen type I (Col-I), AT1R and nuclear factor kappaappaB (NF-kappaB) protein
      expression levels were detected using Western blot analysis, and NF-kappaB
      nuclear translocation was measured using immunofluorescence localization
      analysis. Ang II levels in HLF-1 cells were measured with an enzyme-linked
      immunosorbent assay (ELISA). We found that hypoxia increased Col-I mRNA and
      protein expression in HLF-1 cells, and this effect could be inhibited by an AT1R
      or AT2R inhibitor. The levels of NF-kappaB, RAS components and Ang II production
      in HLF-1 cells were significantly increased after the hypoxia exposure. Hypoxia
      or Ang II increased NF-kappaB-p50 protein expression in HLF-1 cells, and the
      special effect could be inhibited by telmisartan (TST), an AT1R inhibitor, and
      partially inhibited by PD123319, an AT2R inhibitor. Importantly, hypoxia-induced
      NF-kappaB nuclear translocation could be nearly completely inhibited by an AT1R
      or AT2R inhibitor. Furthermore pyrrolidine dithiocarbamate (PDTC), a NF-kappaB
      blocker, abolished the expression of hypoxia-induced AT1R and Col-I in HLF-1
      cells. Our results indicate that Ang II-mediated NF-kappaB signalling via ATR is
      involved in hypoxia-induced collagen synthesis in human lung fibroblasts.

PMID- 24336064
TI  - Biodegradation of di-n-butyl phthalate by a newly isolated halotolerant
      Sphingobium sp.
AB  - A Gram-negative strain (TJ) capable of growing aerobically on mixed phthalate
      esters (PAEs) as the sole carbon and energy source was isolated from the Haihe
      estuary, Tianjin, China. It was identified as belonging to the Sphingobium genus
      on the basis of morphological and physiological characteristics and 16S rRNA and
      gyrb gene sequencing. The batch tests for biodegradation of di-n-butyl phthalate
      (DBP) by the Sphingobium sp. TJ showed that the optimum conditions were 30 
      degrees C, pH 7.0, and the absence of NaCl. Stain TJ could tolerate up to 4% NaCl
      in minimal salt medium supplemented with DBP, although the DBP degradation rates
      slowed as NaCl concentration increased. In addition, substrate tests showed that
      strain TJ could utilize shorter side-chained PAEs, such as dimethyl phthalate and
      diethyl phthalate, but could not metabolize long-chained PAEs, such as di-n-octyl
      phthalate, diisooctyl phthalate, and di-(2-ethyl-hexyl) phthalate. To our
      knowledge, this is the first report on the biodegradation characteristics of DBP
      by a member of the Sphingobium genus.

PMID- 24336065
TI  - The effects of H2S on the activities of CYP2B6, CYP2D6, CYP3A4, CYP2C19 and
      CYP2C9 in vivo in rat.
AB  - Hydrogen sulfide (H2S) is a colorless, flammable, extremely hazardous gas with a
      "rotten egg" smell. The human body produces small amounts of H2S and uses it as a
      signaling molecule. The cocktail method was used to evaluate the influence of H2S
      on the activities of CYP450 in rats, which were reflected by the changes of
      pharmacokinetic parameters of five specific probe drugs: bupropion, metroprolol,
      midazolam, omeprazole and tolbutamide, respectively. The rats were randomly
      divided into two groups, control group and H2S group. The H2S group rats were
      given 5 mg/kg NaHS by oral administration once a day for seven days. The mixture
      of five probes was given to rats through oral administration and the blood
      samples were obtained at a series of time-points through the caudal vein. The
      concentrations of probe drugs in rat plasma were measured by LC-MS. In comparing
      the H2S group with the control group, there was a statistically pharmacokinetics
      difference for midazolam and tolbutamide; the area under the plasma concentration
      time curve (AUC) was decreased for midazolam (p < 0.05) and increased for
      tolbutamide (p < 0.05); while there was no statistical pharmacokinetics
      difference for bupropion, metroprolol and omeprazole. H2S could not influence the
      activities of CYP2B6, CYP2D6 and CYP2C19 in rats, while H2S could induce the
      activity of CYP3A4 and inhibit the activity of CYP2C9 in rats.

PMID- 24336066
TI  - Synthesis and larvicidal activity against Culex pipiens pallens of new triazole
      derivatives of phrymarolin from Phryma leptostachya L.
AB  - Twelve new triazole derivatives of Phrymarolin were prepared from Phrymarolin I
      and the structures of all the derivatives were fully characterized by (1)H-NMR,
      (13)C-NMR and MS spectral data analyses. Larvicidal activities against 4rd instar
      larvae of Culex pipiens pallens of these Phrymarolin analogues were assayed.
      Although the triazole derivatives of Phrymarolin showed certain larvicidal
      activity, they showed lower activity than Phrymarolin I. The typical non-natural
      groups triazole substituents reduced the larvicidal activity of Phrymarolin
      derivatives.

PMID- 24336067
TI  - Nutlin-3a efficacy in sarcoma predicted by transcriptomic and epigenetic
      profiling.
AB  - Nutlin-3a is a small-molecule antagonist of p53/MDM2 that is being explored as a
      treatment for sarcoma. In this study, we examined the molecular mechanisms
      underlying the sensitivity of sarcomas to Nutlin-3a. In an ex vivo tissue explant
      system, we found that TP53 pathway alterations (TP53 status, MDM2/MDM4 genomic
      amplification/mRNA overexpression, MDM2 SNP309, and TP53 SNP72) did not confer
      apoptotic or cytostatic responses in sarcoma tissue biopsies (n = 24).
      Unexpectedly, MDM2 status did not predict Nutlin-3a sensitivity. RNA sequencing
      revealed that the global transcriptomic profiles of these sarcomas provided a
      more robust prediction of apoptotic responses to Nutlin-3a. Expression profiling
      revealed a subset of TP53 target genes that were transactivated specifically in
      sarcomas that were highly sensitive to Nutlin-3a. Of these target genes, the
      GADD45A promoter region was shown to be hypermethylated in 82% of wild-type TP53
      sarcomas that did not respond to Nutlin-3a, thereby providing mechanistic insight
      into the innate ability of sarcomas to resist apoptotic death following Nutlin-3a
      treatment. Collectively, our findings argue that the existing benchmark biomarker
      for MDM2 antagonist efficacy (MDM2 amplification) should not be used to predict
      outcome but rather global gene expression profiles and epigenetic status of
      sarcomas dictate their sensitivity to p53/MDM2 antagonists.

PMID- 24336068
TI  - A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells.
AB  - Immune escape is a fundamental trait of cancer in which mechanistic knowledge is
      incomplete. Here, we describe a novel mechanism by which hypoxia contributes to
      tumoral immune escape from cytotoxic T lymphocytes (CTL). Exposure of human or
      murine cancer cells to hypoxia for 24 hours led to upregulation of the immune
      inhibitory molecule programmed cell death ligand-1 (PD-L1; also known as B7-H1),
      in a manner dependent on the transcription factor hypoxia-inducible factor-1alpha
      (HIF-1alpha). In vivo studies also demonstrated cellular colocalization of HIF
      1alpha and PD-L1 in tumors. Hypoxia-induced expression of PD-L1 in cancer cells
      increased their resistance to CTL-mediated lysis. Using glyceryl trinitrate
      (GTN), an agonist of nitric oxide (NO) signaling known to block HIF-1alpha
      accumulation in hypoxic cells, we prevented hypoxia-induced PD-L1 expression and
      diminished resistance to CTL-mediated lysis. Moreover, transdermal administration
      of GTN attenuated tumor growth in mice. We found that higher expression of PD-L1
      induced in tumor cells by exposure to hypoxia led to increased apoptosis of
      cocultured CTLs and Jurkat leukemia T cells. This increase in apoptosis was
      prevented by blocking the interaction of PD-L1 with PD-1, the PD-L1 receptor on T
      cells, or by addition of GTN. Our findings point to a role for hypoxia/HIF-1 in
      driving immune escape from CTL, and they suggest a novel cancer immunotherapy to
      block PD-L1 expression in hypoxic-tumor cells by administering NO mimetics.

PMID- 24336069
TI  - Differentially expressed genes in autosomal dominant osteopetrosis type II
      osteoclasts reveal known and novel pathways for osteoclast biology.
AB  - Autosomal dominant osteopetrosis type II (ADO II) is a rare, heritable bone
      disorder characterized by a high bone mass and insufficient osteoclast activity.
      Mutations in the CLCN7 gene have been reported to cause ADO II. To gain novel
      insights into the pathways dysregulated in ADOII osteoclasts, we identified
      changes in gene expression in osteoclasts from patients with a heterozygous
      mutation of CLCN7. To do this, we carried out a transcriptomic study comparing
      gene expression in the osteoclasts of patients with ADO II and healthy donors.
      Our data show that, according to our selection criteria, 182 genes were
      differentially expressed in osteoclasts from patients and controls. From the 18
      displaying the highest change in microarray, we confirmed differential expression
      for seven by qPCR. Although two of them have previously been found to be
      expressed in osteoclasts (ITGB5 and SERPINE2), the other five (CES1 (carboxyl
      esterase 1), UCHL1 (ubiquitin carboxy-terminal esterase L1, also known as
      ubiquitin thiolesterase), WARS (tryptophanyl-tRNA synthetase), GBP4 (guanylate
      binding protein 4), and PRF1) are not yet known to have a role in this cell type.
      At the protein level, we confirmed elevated expression of ITGB5 and reduced
      expression of WARS, PRF1, and SERPINE2. Transfection of ClC-7 harboring the G215R
      mutation into osteoclasts resulted in an increased ITGB5 and reduced PRF1
      expression of borderline significance. Finally, we observed that the ADO II
      patients presented a normal or increased serum level of bone formation markers,
      demonstrating a coupling between dysfunctional osteoclasts and osteoblasts.
      Sphingosine kinase 1 mRNA was expressed at the same level in ADO II and control
      osteoclasts. In conclusion, these data suggest that in addition to an
      acidification dysfunction caused by the CLCN7 mutation, a change in ITGB5, PRF1,
      WARS, and SERPINE2 expression could be part of the osteoclastic phenotype of ADO
      II. 

PMID- 24336071
TI  - Analysis of circulating microRNAs in adrenocortical tumors.
AB  - Differential diagnosis of adrenocortical adenoma (ACA) and carcinoma is of
      pivotal clinical relevance, as the prognosis and clinical management of benign
      and malignant adrenocortical tumors (ACTs) is entirely different. Circulating
      microRNAs (miRNAs) are promising biomarker candidates of malignancy in several
      tumors; however, there are still numerous technical problems associated with
      their analysis. The objective of our study was to investigate circulating miRNAs
      in ACTs and to evaluate their potential applicability as biomarkers of
      malignancy. We have also addressed technical questions including the choice of
      profiling and reference gene used. A total of 25 preoperative plasma samples
      obtained from patients with ACAs and carcinomas were studied by microarray and
      quantitative real-time PCR. None of the three miRNAs (hsa-miR-192, hsa-mir-197
      and hsa-miR-1281) found as differentially expressed in plasma samples in our
      microarray screening could be validated by quantitative real-time PCR. In
      contrast, of the selected eight miRNAs reported in the literature as
      differentially expressed in ACT tissues, five (hsa-miR-100, hsa-miR-181b, hsa-miR
      184, hsa-miR-210 and hsa-miR-483-5p) showed a statistically significant
      overexpression in adrenocortical cancer vs adenoma when normalized on hsa-miR-16
      as a reference gene. Receiver operator characteristic analysis of data revealed
      that the combination of dCThsa-miR-210 - dCThsa-miR-181b and dCThsa-miR
      100/dCThsa-miR-181b showed the highest diagnostic accuracy (area under curve 0.87
      and 0.85, respectively). In conclusion, we have found significant differences in
      expression of circulating miRNAs between ACAs and carcinomas, but their
      diagnostic accuracy is not yet high enough for clinical application. Further
      studies on larger cohorts of patients are needed to assess the diagnostic and
      prognostic potential application of circulating miRNA markers. 

PMID- 24336072
TI  - Truncated Cables1 causes agenesis of the corpus callosum in mice.
AB  - Agenesis of the corpus callosum (ACC) is a congenital abnormality of the brain
      structure. More than 60 genes are known to be involved in corpus callosum
      development. However, the molecular mechanisms underlying ACC are not fully
      understood. Previously, we produced a novel transgenic mouse strain, TAS,
      carrying genes of the tetracycline-inducible expression system that are not
      involved in brain development, and inherited ACC was observed in the brains of
      all homozygous TAS mice. Although ACC was probably induced by transgene insertion
      mutation, the causative gene and the molecular mechanism of its pathogenesis
      remain unclear. Here, we first performed interphase three-color fluorescence in
      situ hybridization (FISH) analysis to determine the genomic insertion site.
      Transgenes were inserted into chromosome 18 ~12.0 Mb from the centromere. Gene
      expression analysis and genomic PCR walking showed that the genomic region
      containing exon 4 of Cables1 was deleted by transgene insertion and the other
      exons of Cables1 were intact. The mutant allele was designated as Cables1(TAS).
      Interestingly, Cables1(TAS) mRNA consisted of exons 1-3 of Cables1 and part of
      the transgene that encoded a novel truncated Cables1 protein. Homozygous TAS mice
      exhibited mRNA expression of Cables1(TAS) in the fetal cerebrum, but not that of
      wild-type Cables1. To investigate whether a dominant negative effect of
      Cables1(TAS) or complete loss of function of Cables1 gives rise to ACC, we
      produced Cables1-null mutant mice. ACC was not observed in Cables1-null mutant
      mice, suggesting that a dominant negative effect of Cables1(TAS) impairs callosal
      formation. Moreover, ACC frequency in Cables1(+/TAS) mice was significantly lower
      than that in Cables1(-/TAS) mice, indicating that wild-type Cables1 interfered
      with the dominant negative effect of Cables1(TAS). This study indicated that
      truncated Cables1 causes ACC and wild-type Cables1 contributes to callosal
      formation. 

PMID- 24336070
TI  - Aging and HIV/AIDS: pathogenetic role of therapeutic side effects.
AB  - The intersection of aging and HIV/AIDS is a looming 'epidemic within an
      epidemic.' This paper reviews how HIV/AIDS and its therapy cause premature aging
      or contribute mechanistically to HIV-associated non-AIDS illnesses (HANA).
      Survival with HIV/AIDS has markedly improved by therapy combinations containing
      nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse
      transcriptase inhibitors, and protease inhibitors (PIs) called HAART (highly
      active antiretroviral therapy). Because NRTIs and PIs together prevent or
      attenuate HIV-1 replication, and prolong life, the population of aging patients
      with HIV/AIDS increases accordingly. However, illnesses frequently associated
      with aging in the absence of HIV/AIDS appear to occur prematurely in HIV/AIDS
      patients. Theories that help to explain biological aging include oxidative stress
      (where mitochondrial oxidative injury exceeds antioxidant defense), chromosome
      telomere shortening with associated cellular senescence, and accumulation of
      lamin A precursors (a nuclear envelop protein). Each of these has the potential
      to be enhanced or caused by HIV/AIDS, antiretroviral therapy, or both.
      Antiretroviral therapy has been shown to enhance events seen in biological aging.
      Specifically, antiretroviral NRTIs cause mitochondrial dysfunction, oxidative
      stress, and mitochondrial DNA defects that resemble features of both HANA and
      aging. More recent clinical evidence points to telomere shortening caused by NRTI
      triphosphate-induced inhibition of telomerase, suggesting telomerase reverse
      transcriptase (TERT) inhibition as being a pathogenetic contributor to premature
      aging in HIV/AIDS. PIs may also have a role in premature aging in HIV/AIDS as
      they cause prelamin A accumulation. Overall, toxic side effects of HAART may both
      resemble and promote events of aging and are worthy of mechanistic studies. 

PMID- 24336073
TI  - miR-16 and miR-26a target checkpoint kinases Wee1 and Chk1 in response to p53
      activation by genotoxic stress.
AB  - The tumour suppressor p53 is a crucial regulator of cell cycle arrest and
      apoptosis by acting as a transcription factor to regulate a variety of genes. At
      least in part, this control is exerted by p53 via regulating expression of
      numerous microRNAs. We identified two abundantly expressed microRNAs, miR-16 and
      miR-26a, whose expression is regulated by p53 during the checkpoint arrest
      induced by the genotoxic drug, doxorubicin. Importantly, among the targets of
      these miRs are two critical checkpoint kinases, Chk1 and Wee1. The p53-dependent
      augmentation of miR-16 and miR-26a expression levels led to the cell cycle arrest
      of tumour cells in G1/S and increased apoptosis. Strikingly, the bioinformatics
      analysis of survival times for patients with breast and prostate cancers has
      revealed that co-expression of mir-16 and miR-26a correlated with a better
      survival outcome. Collectively, our data provide a novel mechanism whereby p53
      represses Chk1 and Wee1 expression, at least partially, via upregulation of miR
      16 and miR-26a and thus sensitizes tumour cells to genotoxic therapies. 

PMID- 24336074
TI  - ADAM17 is a survival factor for microglial cells in vitro and in vivo after
      spinal cord injury in mice.
AB  - A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important
      substrates including tumor necrosis factor-alpha (TNF-alpha) and its receptors,
      the p75 neurotrophin receptor (p75NTR), and members of the epidermal growth
      factor family. The rationale of this study was to inhibit ADAM17-induced shedding
      of soluble TNF-alpha in order to reduce detrimental inflammation after spinal
      cord injury (SCI). However, using the specific ADAM17 blocker BMS-561392 in
      neuronal and glial cell cultures, we show that proper functioning of ADAM17 is
      vital for oligodendrocyte and microglia survival in a p44 MAPK-dependent manner.
      In contrast, genetic ablation of ADAM17 specifically increases microglial death.
      Surprisingly, although blocking ADAM17 in vivo does not substantially change the
      ratio between membrane-bound and soluble TNF-alpha, it increases expression of
      the pro-apoptotic marker Bax and microglial apoptosis while impairing functional
      recovery after SCI. These data suggest that ADAM17 is a key survival factor for
      microglial cells after SCI. 

PMID- 24336075
TI  - Dual role of the caspase enzymes in satellite cells from aged and young subjects.
AB  - Satellite cell (SC) proliferation and differentiation have critical roles in
      skeletal muscle recovery after injury and adaptation in response to hypertrophic
      stimuli. Normal ageing hinders SC proliferation and differentiation, and is
      associated with increased expression of a number of pro-apoptotic factors in
      skeletal muscle. In light of previous studies that have demonstrated age-related
      altered expression of genes involved in SC antioxidant and repair activity, this
      investigation was aimed at evaluating the incidence of apoptotic features in
      human SCs. Primary cells were obtained from vastus lateralis of nine young
      (27.3+/-2.0 years old) and nine old (71.1+/-1.8 years old) subjects, and cultured
      in complete medium for analyses at 4, 24, 48, and 72 h. Apoptosis was assessed
      using AnnexinV/propidium iodide staining, the terminal deoxynucleotidyl
      transferase dUTP nick-end labelling technique, RT-PCR, DNA microarrays, flow
      cytometry, and immunofluorescence analysis. There was an increased rate of
      apoptotic cells in aged subjects at all of the experimental time points, with no
      direct correlation between AnnexinV-positive cells and caspase-8 activity. On the
      other hand, CASP2, CASP6, CASP7, and CASP9 and a number of cell death genes were
      upregulated in the aged SCs. Altogether, our data show age-related enhanced
      susceptibility of human SCs to apoptosis, which might be responsible for their
      reduced response to muscle damage. 

PMID- 24336076
TI  - The Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin increases cisplatin
      antitumor activity by inducing p53-mediated apoptosis in head and neck cancer.
AB  - The tumor suppressor p53 is often inactivated in head and neck cancer (HNC)
      through TP53 mutations or overexpression of mouse double minute 2 or mouse double
      minute X. Restoration of p53 function by counteracting these p53 repressors is a
      promising strategy for cancer treatment. The present study assessed the ability
      of a heat shock protein 90 (Hsp90) inhibitor, 17-(Allylamino)-17
      demethoxygeldanamycin (17AAG), to induce apoptosis in HNC by restoring p53
      function. The effect of 17AAG, alone or in combination with Nutlin-3a or
      cisplatin, was assessed in HNC cells using growth and apoptosis, immunoblotting,
      quantitative reverse transcription-polymerase chain reaction, and preclinical
      tumor xenograft models. 17AAG activated and stabilized p53 in HNC cells bearing
      wild-type TP53 by disrupting the p53-MDMX interaction. 17AAG upregulated p21 and
      proapoptotic gene expression, and promoted apoptosis in a concentration-dependent
      manner. Growth inhibition by 17AAG was highest in tumor cells with MDMX
      overexpression. The apoptotic response was blocked by inhibition of p53
      expression, demonstrating that the effect of 17AAG depended on p53 and MDMX.
      17AAG synergized in vitro with Nutlin-3a and in vitro and in vivo with cisplatin
      to induce p53-mediated apoptosis. 17AAG effectively induced p53-mediated
      apoptosis in HNC cells through MDMX inhibition and increased the antitumor
      activity of cisplatin synergistically, suggesting a promising strategy for
      treating HNC. 

PMID- 24336077
TI  - Mycobacterial HBHA induces endoplasmic reticulum stress-mediated apoptosis
      through the generation of reactive oxygen species and cytosolic Ca2+ in murine
      macrophage RAW 264.7 cells.
AB  - Mycobacterial heparin-binding haemagglutinin antigen (HBHA) is a virulence factor
      that induces apoptosis of macrophages. Endoplasmic reticulum (ER) stress-mediated
      apoptosis is an important regulatory response that can be utilised to study the
      pathogenesis of tuberculosis. In the present study, HBHA stimulation induced ER
      stress sensor molecules in a caspase-dependent manner. Pre-treatment of RAW 264.7
      cells with an IkappaB kinase 2 inhibitor reduced not only C/EBP homology protein
      expression but also IL-6 and monocyte chemotactic protein-1 (MCP-1) production.
      BAPTA-AM reduced both ER stress responses and caspase activation and strongly
      suppressed HBHA-induced IL-6 and MCP-1 production in RAW 264.7 cells. Enhanced
      reactive oxygen species (ROS) production and elevated cytosolic [Ca(2+)]i levels
      were essential for HBHA-induced ER stress responses. Collectively, our data
      suggest that HBHA induces cytosolic [Ca(2+)]i, which influences the generation of
      ROS associated with the production of proinflammatory cytokines. These concerted
      and complex cellular responses induce ER stress-associated apoptosis during HBHA
      stimulation in macrophages. These results indicate that the ER stress pathway has
      an important role in the HBHA-induced apoptosis during mycobacterial infection. 

PMID- 24336078
TI  - Placenta-derived mesenchymal stem cells improve memory dysfunction in an Abeta1
      42-infused mouse model of Alzheimer's disease.
AB  - Mesenchymal stem cells (MSCs) promote functional recoveries in pathological
      experimental models of central nervous system (CNS) and are currently being
      tested in clinical trials for neurological disorders, but preventive mechanisms
      of placenta-derived MSCs (PD-MSCs) for Alzheimer's disease are poorly understood.
      Herein, we investigated the inhibitory effect of PD-MSCs on neuronal cell death
      and memory impairment in Abeta1-42-infused mice. After intracerebroventrical
      (ICV) infusion of Abeta1-42 for 14 days, the cognitive function was assessed by
      the Morris water maze test and passive avoidance test. Our results showed that
      the transplantation of PD-MSCs into Abeta1-42-infused mice significantly improved
      cognitive impairment, and behavioral changes attenuated the expression of APP,
      BACE1, and Abeta, as well as the activity of beta-secretase and gamma-secretase.
      In addition, the activation of glia cells and the expression of inducible nitric
      oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by the
      transplantation of PD-MSCs. Furthermore, we also found that PD-MSCs downregulated
      the release of inflammatory cytokines as well as prevented neuronal cell death
      and promoted neuronal cell differentiation from neuronal progenitor cells in
      Abeta1-42-infused mice. These data indicate that PD-MSC mediates neuroprotection
      by regulating neuronal death, neurogenesis, glia cell activation in hippocampus,
      and altering cytokine expression, suggesting a close link between the therapeutic
      effects of MSCs and the damaged CNS in Alzheimer's disease. 

PMID- 24336080
TI  - Involvement of miR-9/MCPIP1 axis in PDGF-BB-mediated neurogenesis in neuronal
      progenitor cells.
AB  - Highly conserved microRNA-9 (miR-9) has a critical role in various cellular
      processes including neurogenesis. However, its regulation by neurotropins that
      are known to mediate neurogenesis remains poorly defined. In this study, we
      identify platelet-derived growth factor-BB (PDGF-BB)-mediated upregulation of miR
      9, which in turn downregulates its target gene monocyte chemotactic protein
      induced protein 1 (MCPIP1), as a key player in modulating proliferation, neuronal
      differentiation as well as migration of neuronal progenitor cells (NPCs). Results
      indicate that miR-9-mediated NPC proliferation and neuronal differentiation
      involves signaling via the nuclear factor-kappa B (NF-kappaB) and cAMP response
      element-binding protein (CREB) pathways, and that NPC migration involves CREB but
      not the NF-kappaB signaling. These findings thus suggest that miR-9-mediated
      downregulation of MCPIP1 acts as a molecular switch regulation of neurogenesis. 

PMID- 24336079
TI  - Dysregulated microRNAs in amyotrophic lateral sclerosis microglia modulate genes
      linked to neuroinflammation.
AB  - MicroRNAs (miRNAs) regulate gene expression at post-transcriptional level and are
      key modulators of immune system, whose dysfunction contributes to the progression
      of neuroinflammatory diseaseas such as amyotrophic lateral sclerosis (ALS), the
      most widespread motor neuron disorder. ALS is a non-cell-autonomous disease
      targeting motor neurons and neighboring glia, with microgliosis directly
      contributing to neurodegeneration. As limited information exists on miRNAs
      dysregulations in ALS, we examined this topic in primary microglia from
      superoxide dismutase 1-G93A mouse model. We compared miRNAs transcriptional
      profiling of non-transgenic and ALS microglia in resting conditions and after
      inflammatory activation by P2X7 receptor agonist. We identified upregulation of
      selected immune-enriched miRNAs, recognizing miR-22, miR-155, miR-125b and miR
      146b among the most highly modulated. We proved that miR-365 and miR-125b
      interfere, respectively, with the interleukin-6 and STAT3 pathway determining
      increased tumor necrosis factor alpha (TNFalpha) transcription. As TNFalpha
      directly upregulated miR-125b, and inhibitors of miR-365/miR-125b reduced
      TNFalpha transcription, we recognized the induction of miR-365 and miR-125b as a
      vicious gateway culminating in abnormal TNFalpha release. These results
      strengthen the impact of miRNAs in modulating inflammatory genes linked to ALS
      and identify specific miRNAs as pathogenetic mechanisms in the disease. 

PMID- 24336081
TI  - TNF/TNF-R1 pathway is involved in doxorubicin-induced acute sterile inflammation.

PMID- 24336082
TI  - Lipopolysaccharide sensitized male and female juvenile brains to ionizing
      radiation.
AB  - Radiotherapy is an effective tool in the treatment of pediatric malignancies but
      it is associated with adverse side effects, both short- and long-term. One common
      long-term side effect after cranial radiotherapy is cognitive impairment and this
      is, at least partly, thought to be caused by reduced hippocampal neurogenesis.
      Neuroinflammation and a perturbed microenvironment are thought to be important in
      the dysregulation of neurogenesis seen after irradiation (IR). We investigated
      the effects of a pre-existing, lipopolysaccharide (LPS)-induced systemic
      inflammation at the time of IR in both males and females. A single dose of 8 Gy
      to the brain of postnatal day 14 mice caused an upregulation of
      cytokines/chemokines (IL-1beta, MIP-1beta, IL-12, GM-CSF, MIP-1alpha, IL-17, CCL2
      and KC) 6 h after IR, more so in females. Caspase-3 activity, reflecting
      apoptosis and possibly microglia activation, was elevated 6 h after IR. Females
      treated with LPS before IR showed a higher caspase-3 activity compared with
      males. During the chronic phase (3 months post IR), we found that LPS-induced
      inflammation at the time of IR aggravated the IR-induced injury in both male and
      female mice, as judged by reduced bromodeoxyuridine incorporation and
      neurogenesis (doublecortin-positive cells) in the hippocampus. At this late time
      point, the microglia density was increased by IR, more so in females, indicating
      long-term effects on the microenvironment. IR increased anxiety-related behavior
      in vehicle-, but not LPS-, treated animals. However, exploratory behavior was
      affected by IR in both vehicle- and LPS-treated mice. In conclusion, we found
      that LPS administration before IR of the young mouse brain aggravated the injury,
      as judged by reduced hippocampal neurogenesis. This supports the clinical
      practice to postpone radiotherapy if the patient shows signs of infection.
      Systemic inflammation is not always obvious, though, for example because of
      concurrent corticosteroid treatment, so careful monitoring of inflammation is
      warranted. 

PMID- 24336083
TI  - PATZ1 interacts with p53 and regulates expression of p53-target genes enhancing
      apoptosis or cell survival based on the cellular context.
AB  - PATZ1 is a transcriptional factor functioning either as an activator or a
      repressor of gene transcription depending upon the cellular context. It appears
      to have a dual oncogenic/anti-oncogenic activity. Indeed, it is overexpressed in
      colon carcinomas, and its silencing inhibits colon cancer cell proliferation or
      increases sensitivity to apoptotic stimuli of glioma cells, suggesting an
      oncogenic role. Conversely, the development of B-cell lymphomas, sarcomas,
      hepatocellular carcinomas and lung adenomas in Patz1-knockout (ko) mice supports
      its tumour suppressor function. PATZ1 role in mouse lymphomagenesis is mainly
      because of the involvement of PATZ1 in BCL6-negative autoregulation. However,
      this does not exclude that PATZ1 may be involved in tumorigenesis by other
      mechanisms. Here, we report that PATZ1 interacts with the tumour suppressor p53
      and binds p53-dependent gene promoters, including those of BAX, CDKN1A and MDM2.
      Knockdown of PATZ1 in HEK293 cells reduces promoter activity of these genes and
      inhibits their expression, suggesting a role of PATZ in enhancing p53
      transcriptional activity. Consistently, Patz1-ko mouse embryonic fibroblasts
      (MEFs) show decreased expression of Bax, Cdkn1a and Mdm2 compared with wild-type
      (wt) MEFs. Moreover, Patz1-ko MEFs show a decreased percentage of apoptotic
      cells, either spontaneous or induced by treatment with 5-fluorouracil (5FU),
      compared with wt controls, suggesting a pro-apoptotic role for PATZ1 in these
      cells. However, PATZ1 binds p53-target genes also independently from p53,
      exerting, in the absence of p53, an opposite function on their expression.
      Indeed, knockdown of PATZ1 in p53-null osteosarcoma cells upregulates BAX
      expression and decreases survival of 5FU-treated cells, then suggesting an anti
      apoptotic role of PATZ1 in p53-null cancer cells. Therefore, these data support a
      PATZ1 tumour-suppressive function based on its ability to enhance p53-dependent
      transcription and apoptosis. Conversely, its opposite and anti-apoptotic role in
      p53-null cancer cells provides the perspective of PATZ1 silencing as a possible
      adjuvant in the treatment of p53-null cancer. 

PMID- 24336085
TI  - Induction of necrotic cell death by oxidative stress in retinal pigment
      epithelial cells.
AB  - Age-related macular degeneration (AMD) is a degenerative disease of the retina
      and the leading cause of blindness in the elderly. Retinal pigment epithelial
      (RPE) cell death and the resultant photoreceptor apoptosis are characteristic of
      late-stage dry AMD, especially geographic atrophy (GA). Although oxidative stress
      and inflammation have been associated with GA, the nature and underlying
      mechanism for RPE cell death remains controversial, which hinders the development
      of targeted therapy for dry AMD. The purpose of this study is to systematically
      dissect the mechanism of RPE cell death induced by oxidative stress. Our results
      show that characteristic features of apoptosis, including DNA fragmentation,
      caspase 3 activation, chromatin condensation and apoptotic body formation, were
      not observed during RPE cell death induced by either hydrogen peroxide or tert
      Butyl hydroperoxide. Instead, this kind of cell death can be prevented by RIP
      kinase inhibitors necrostatins but not caspase inhibitor z-VAD, suggesting
      necrotic feature of RPE cell death. Moreover, ATP depletion, receptor interacting
      protein kinase 3 (RIPK3) aggregation, nuclear and plasma membrane leakage and
      breakdown, which are the cardinal features of necrosis, were observed in RPE
      cells upon oxidative stress. Silencing of RIPK3, a key protein in necrosis,
      largely prevented oxidative stress-induced RPE death. The necrotic nature of RPE
      death is consistent with the release of nuclear protein high mobility group
      protein B1 into the cytoplasm and cell medium, which induces the expression of
      inflammatory gene TNFalpha in healthy RPE and THP-1 cells. Interestingly,
      features of pyroptosis or autophagy were not observed in oxidative stress-treated
      RPE cells. Our results unequivocally show that necrosis, but not apoptosis, is a
      major type of cell death in RPE cells in response to oxidative stress. This
      suggests that preventing oxidative stress-induced necrotic RPE death may be a
      viable approach for late-stage dry AMD. 

PMID- 24336084
TI  - TOR-centric view on insulin resistance and diabetic complications: perspective
      for endocrinologists and gerontologists.
AB  - This article is addressed to endocrinologists treating patients with diabetic
      complications as well as to basic scientists studying an elusive link between
      diseases and aging. It answers some challenging questions. What is the link
      between insulin resistance (IR), cellular aging and diseases? Why complications
      such as retinopathy may paradoxically precede the onset of type II diabetes. Why
      intensive insulin therapy may initially worsen retinopathy. How nutrient- and
      insulin-sensing mammalian target of rapamycin (mTOR) pathway can drive insulin
      resistance and diabetic complications. And how rapamycin, at rational doses and
      schedules, may prevent IR, retinopathy, nephropathy and beta-cell failure,
      without causing side effects. 

PMID- 24336086
TI  - Strange attractors: DAMPs and autophagy link tumor cell death and immunity.
AB  - Resistance to 'apoptotic' cell death is one of the major hallmarks of cancer,
      contributing to tumor development and therapeutic resistance. Damage-associated
      molecular patterns (DAMPs) are molecules released or exposed by dead, dying,
      injured, or stressed non-apoptotic cells, with multiple roles in inflammation and
      immunity. Release of DAMPs not only contributes to tumor growth and progression
      but also mediates skewing of antitumor immunity during so-called immunogenic
      tumor cell death (ICD). Autophagy is a lysosome-mediated homeostatic degradation
      process in which cells digest their own effete organelles and macromolecules to
      meet bioenergetic needs and enable protein synthesis. For tumor cells, autophagy
      is a double-edged sword. Autophagy, in balance with apoptosis, can function as a
      tumor suppressor; autophagy deficiency, associated with alterations in apoptosis,
      initiates tumorigenesis in many settings. In contrast, autophagy-related stress
      tolerance generally promotes cell survival, which enables tumor growth and
      promotes therapeutic resistance. Most anticancer therapies promote DAMP release
      and enhance autophagy. Autophagy not only regulates DAMP release and degradation,
      but also is triggered and regulated by DAMPs. This interplay between autophagy
      and DAMPs, serving as 'strange attractors' in the dynamic system that emerges in
      cancer, regulates the effectiveness of antitumor treatment. This interplay also
      shapes the immune response to dying cells upon ICD, culling the least fit tumor
      cells and promoting survival of others. Thus, DAMPs and autophagy are suitable
      emergent targets for cancer therapy, considering their more nuanced role in tumor
      progression. 

PMID- 24336088
TI  - Impact of social-psychiatric services and psychiatric clinics on involuntary
      admissions.
AB  - BACKGROUND: Germany provides a wide range of highly developed mental health care
      to its citizens. The aim of this study was to identify factors influencing the
      voluntariness of admissions to psychiatric hospitals. Especially the impact of
      demographic factors of the region, characteristics of the psychiatric hospitals
      and characteristics of the psychosocial services was analyzed. METHOD: A
      retrospective analysis of hospital admission registers from 13 German adult
      psychiatric hospitals in 2009 was conducted. Public data on the regional
      psychiatric accommodation and demographic situation were added. Hospitals were
      dichotomously divided according to their index of involuntary admissions. Group
      comparisons were performed between the clinics with low and high involuntary
      admission indices. Analysis was conducted with clinical, psychiatric provision
      and demographic data related to inpatients in the Landschaftsverbands Westfalen
      Lippe (LWL)-PsychiatryNetwork. RESULTS: Especially the range of services provided
      by the social-psychiatric services in the region such as number of supervised
      patients and home visits had an influence on the proportion of involuntary
      admissions to a psychiatric hospital. Some demographic characteristics of the
      region such as discretionary income showed further influence. Contrary to our
      expectations, the characteristics of the individual hospital seem to have no
      influence on the admission rate. CONCLUSION: Social-psychiatric services show a
      preventive impact on involuntary acute psychiatry interventions. Sociodemographic
      factors and patient variables play a role with regard to the number of
      involuntary hospitalizations, whereas characteristics of hospitals seemed to play
      no role.

PMID- 24336087
TI  - Functional RIG-I-like receptors control the survival of mesenchymal stem cells.
AB  - Because of their potent regenerative and immunomodulatory properties, mesenchymal
      stem cells (MSCs) have promising therapeutic benefits in clinical treatment of
      inflammatory and infectious diseases. Recent studies suggest that many biological
      activities of MSCs are largely determined by pattern recognition receptors
      (PRRs), such as Toll-like receptors (TLRs). However, the role of PRRs in
      regulating the survival of MSCs remains unknown. In the present study, we
      examined the viability of MSCs after stimulation of distinct PRRs. Activation of
      TLRs by direct addition with their respective ligands showed no significant
      effect on the survival of MSCs, whereas transfection with double-stranded RNA
      (dsRNA) resulted in marked cell death in MSCs. Transfection of dsRNA upregulated
      cytosolic retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including
      RIG-I and melanoma differentiation-associated antigen 5 (MDA5). Moreover,
      transfection of dsRNA activated downstream transcription factors interferon
      regulatory factor 3 (IRF3) and nuclear factor kappaB (NF-kappaB), as well as
      induced the expression of interferon-beta (IFN-beta) and pro-inflammatory
      cytokine interleukin 6 (IL-6) via RLR signaling. Furthermore, we found that
      transfection of dsRNA triggered both extrinsic and intrinsic apoptotic responses
      via RLRs. However, ectopic expression of RIG-I or MDA5 was not sufficient to
      induce apoptosis of MSCs without dsRNA transfection. Our study also revealed that
      IkappaB kinase alpha/beta (IKKalpha/beta) was required for RLR-mediated apoptosis
      in MSCs, while TANK-binding kinase 1 (TBK1)/IKKE served a pro-survival role.
      Moreover, neither overexpression of B-cell lymphoma 2 (Bcl2) nor neutralizing
      autocrined IFN-beta reduced RLR-mediated apoptosis. In addition, autophagy was
      induced upon activation of RLRs, however, blocking autophagy did not rescue MSCs
      from the dsRNA-induced cell death. To the best of our knowledge, this is the
      first study to explore the role of RLRs in controlling the survival of MSCs,
      which may provide a clue to understand the pathogenesis of viral infection in
      MSCs. 

PMID- 24336089
TI  - Later school start time is associated with improved sleep and daytime functioning
      in adolescents.
AB  - OBJECTIVE: Chronic insufficient sleep is a growing concern among adolescents and
      is associated with a host of adverse health consequences. Early school start
      times may be an environmental contributor to this problem. The purpose of this
      study was to examine the impact of a delay in school start time on sleep
      patterns, sleepiness, mood, and health-related outcomes. METHOD: Boarding
      students (n = 197, mean age = 15.6 yr) attending an independent high school
      completed the School Sleep Habits Survey before and after the school start time
      was experimentally delayed from 8:00 a.m. to 8:25 a.m. RESULTS: The delay in
      school start time was associated with a significant (29 min) increase in sleep
      duration on school nights. The percentage of students receiving 8 or more hours
      of sleep on a school night increased to more than double, from 18% to 44%.
      Students in 9th and 10th grade and those with lower baseline sleep amounts were
      more likely to report improvements in sleep duration after the schedule change.
      Daytime sleepiness, depressed mood, and caffeine use were all significantly
      reduced after the delay in school start time. Sleep duration reverted to baseline
      levels when the original (earlier) school start time was reinstituted.
      CONCLUSIONS: A modest (25 min) delay in school start time was associated with
      significant improvements in sleep duration, daytime sleepiness, mood, and
      caffeine use. These findings have important implications for public policy and
      add to research suggesting the health benefits of modifying school schedules to
      more closely align with adolescents' circadian rhythms and sleep needs.

PMID- 24336090
TI  - The effects of a stress management intervention in elementary school children.
AB  - OBJECTIVE: This preliminary study tests the effectiveness of an elementary school
      based stress management technique on anxiety symptoms and heart rate variability
      (HRV) in children. METHODS: In this controlled prospective longitudinal study,
      children in third-grade classroom participated in a teacher-led daily 10-minute
      stress management intervention for 4 months. The control class teacher read from
      a children's book for 10 minutes daily. A standardized anxiety scale and HRV
      (using computer biofeedback program) were measured before the 4-month
      intervention, immediately after, and 1 year later. RESULTS: The intervention
      class showed significant improvement from baseline to the immediate
      postintervention period in total anxiety (N = 14, F = 12.95, p = .002), with 1
      year follow-up scores maintaining improvement (N = 13, F = 5.88, p = .025). The
      intervention class had small improvement in HRV using the biofeedback program in
      the immediate postintervention period, with significant improvement at 1-year
      follow-up (N = 13, F = 10.61, p = .005). The control class showed no
      improvements. Qualitatively, children reported that the intervention was helpful
      during stressful times at school and at home, even after the study period.
      CONCLUSION: An elementary school-based short daily stress management intervention
      can decrease symptoms of anxiety, and improve HRV, a measure of relaxation.
      Ultimately, these children found this skill continued to help them cope better
      with everyday stressors.

PMID- 24336092
TI  - Ionization of Rydberg atoms by standing-wave light fields.
AB  - When electromagnetic radiation induces atomic transitions, the size of the atom
      is usually much smaller than the wavelength of the radiation, allowing the
      spatial variation of the radiation field's phase to be neglected in the
      description of transition rates. Somewhat unexpectedly, this approximation, known
      as the electric dipole approximation, is still valid for the ionization of
      micrometre-sized atoms in highly excited Rydberg states by laser light with a
      wavelength of about the same size. Here we employ a standing-wave laser field as
      a spatially resolving probe within the volume of a Rydberg atom to show that the
      photoionization process only occurs near the nucleus, within a volume that is
      small with respect to both the atom and the laser wavelength. This evidence
      resolves the apparent inconsistency of the electric dipole approximation's
      validity for photoionization of Rydberg atoms, and it verifies the theory of
      light-matter interaction in a limiting case. 

PMID- 24336091
TI  - Primary care providers' initial treatment decisions and antidepressant
      prescribing for adolescent depression.
AB  - OBJECTIVE: Adolescent depression is a serious and undertreated public health
      problem. Nonetheless, pediatric primary care providers (PCPs) may have low rates
      of antidepressant prescribing due to structural and training barriers. This study
      examined the impact of symptom severity and provider characteristics on initial
      depression treatment decisions in a setting with fewer structural barriers, an
      integrated behavioral health network. METHODS: A cross-sectional survey was
      administered to 58 PCPs within a large pediatric practice network. PCP reports of
      initial treatment decisions were compared in response to 2 vignettes describing
      depressed adolescents with either moderate or severe symptoms. PCP depression
      knowledge, attitudes toward addressing psychosocial concerns, demographics, and
      practice characteristics were measured. RESULTS: Few PCPs (25% for moderate, 32%
      for severe) recommended an antidepressant. Compared with treatment
      recommendations for moderate depression, severe depression was associated with a
      greater likelihood of child psychiatry referral (odds ratio [OR], 5.50; 95%
      confidence interval [CI], 2.47-12.2] p < .001). Depression severity did not
      affect the likelihood of antidepressant recommendation (OR, 1.58 [95% CI, 0.80
      3.11] p = .19). Antidepressants were more likely to be recommended by PCPs with
      greater depression knowledge (OR, 1.72 [95% CI, 1.14-2.59] p = .009) and access
      to an on-site mental health provider (OR, 5.13 [95% CI, 1.24-21.2] p = .02) and
      less likely to be recommended by PCPs who reported higher provider burden when
      addressing psychosocial concerns (OR, 0.85 [95% CI, 0.75-0.98] p = .02).
      CONCLUSION: PCPs infrequently recommended antidepressants for adolescents,
      regardless of depression severity. Continued PCP support through experiential
      training, accounting for provider burden when addressing psychosocial concerns,
      and co-management with mental health providers may increase PCPs' antidepressant
      prescribing.

PMID- 24336093
TI  - A Systematic Review And Individual Patient Data Meta-Analysis On Intraabdominal
      Hypertension In Critically Ill Patients: The Wake-Up Project World Initiative on
      Abdominal Hypertension Epidemiology, a Unifying Project (WAKE-Up!).
AB  - Background: Intraabdominal hypertension (IAH), defined as a pathologically
      increase in intraabdominal pressure, is commonly found in critically ill
      patients. While IAH has been associated with several abdominal as well as extra
      abdominal conditions, few studies have examined the occurrence of IAH in relation
      to mortality. Objective: To evaluate the prognostic role of IAH and its risk
      factors at admission in critically ill patients across a wide range of settings
      and countries. Data sources: An individual patient meta-analysis of all available
      data and a systematic review of published (in full or as abstract) medical
      databases and studies between 1996 and June 2012 were performed. The search was
      limited to "clinical trials" and "randomized controlled trials", "adults", using
      the terms "intraabdominal pressure", "intraabdominal hypertension" combined with
      any of the terms "outcome" and "mortality". All together data on 2707 patients,
      representing 21 centers from 11 countries was obtained. Data on 1038 patients
      were not analysed because of the following exclusion criteria: no IAP value on
      admission (n=712), absence of information on ICU outcome (n=195), age <18 or > 95
      years (n=131). Results: Data from 1669 individual patients (19 centers from 9
      countries) were analyzed in the meta-analysis. Presence of IAH was defined as a
      sustained increase in IAP equal to or above 12 mmHg. At admission the mean
      overall IAP was 9.9+/-5.0 mmHg, with 463 patients (27.7%) presenting IAH with a
      mean IAP of 16.3+/-3.4 mmHg. The only independent predictors for IAH were SOFA
      score and fluid balance on the day of admission. Five hundred thirteen patients
      (30.8%) died in intensive care. The independent predictors for intensive care
      mortality were IAH, SAPS II score, SOFA score and admission category.
      Conclusions: This systematic review and individual patient data meta-analysis
      shows that IAH is frequently present in critically ill patients and it is an
      independent predictor for mortality.

PMID- 24336094
TI  - Multiparametric atomic force microscopy imaging of single bacteriophages
      extruding from living bacteria.
AB  - Force-distance (FD) curve-based atomic force microscopy is a valuable tool to
      simultaneously image the structure and map the biophysical properties of
      biological samples at the nanoscale. Traditionally, FD-based atomic force
      microscopy has been severely limited by its poor temporal and lateral
      resolutions. Here we report the use of advanced FD-based technology combined with
      biochemically sensitive tips to image filamentous bacteriophages extruding from
      living bacteria at unprecedented speed and resolution. Directly correlated
      multiparametric images of the structure, adhesion and elasticity of infected
      bacteria demonstrate that the sites of assembly and extrusion localize at the
      bacterial septum in the form of soft nanodomains surrounded by stiff cell wall
      material. The quantitative nano-bio-imaging method presented here offers a wealth
      of opportunities for mapping the physical properties and molecular interactions
      of complex biosystems, from viruses to tissues. 

PMID- 24336096
TI  - Surgical site infection rates and risk factors in orthopedic pediatric patients
      in Madrid, Spain.
AB  - BACKGROUND: The objective of the study is to study surgical site infection (SSI)
      rates and risk factors in a pediatric population. METHODS: We conducted a
      prospective cohort study to estimate the SSI rate at a national pediatric
      referral center, covering all patients managed at the Orthopedic Surgery
      Department of the Nino Jesus Children's University Teaching Hospital from January
      2010 through December 2012. Risk factors and antibiotic prophylaxis were
      monitored. A comparison between Spanish and US data was performed, with a
      breakdown by National Nosocomial Infection Surveillance risk indices. We also
      conducted a comparative study of SSI rates from 2010 to 2012 to assess the impact
      of the epidemiologic surveillance system. RESULTS: The study population of 1079
      patients had a SSI rate of 2.8%. SSI rates were calculated for spinal fusion and
      other musculoskeletal procedures according to the National Nosocomial Infection
      Surveillance risk index. In the case of other musculoskeletal procedures, our SSI
      rates were 0.8 times lower than the overall Spanish rate, but higher than US
      rates for all risk categories. For spinal fusion procedures, our SSI rates were
      1.2 times higher than the Spanish rates and 3.5 times higher than National
      Nosocomial Infection Surveillance rates. This latter finding should be
      interpreted with caution because it was based on a small sample. The multivariate
      analysis indicated that the only predictive factors of SSI were American Society
      of Anesthesiologists score and age. CONCLUSIONS: The surveillance program showed
      that for clean procedures, SSI incidence decreased from 4% in 2010 to 3.2% in
      2011 and to 2.4% in 2012.

PMID- 24336095
TI  - Aspergillus sensitization or carriage in cystic fibrosis patients.
AB  - BACKGROUND: Aspergillus fumigatus (Af) sensitization and persistent carriage are
      deleterious to lung function, but no consensus has been reached defining these
      medical entities. This work aimed to identify possible predictive factors for
      patients who become sensitized to Af, compared with a control group of non
      sensitized Af carriers. METHODS: Between 1995 and 2007, 117 pediatric patients
      were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1
      were recorded. The presence of Af in sputum, the levels of Af-precipitin, total
      IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were
      divided into 2 groups: (1) "sensitization": level of Af-IgE > 0.35 IU/mL with t
      IgE level < 500 IU/mL and (2) "persistent or transient carriage": Af-IgE level <=
      0.35 IU/mL with either an Af transient or persistent positive culture. A survival
      analysis was performed with the appearance of Af-IgE in serum as an outcome
      variable. RESULTS: Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70%
      of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase
      activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and
      1.9, respectively) were predictive factors for sensitization. We propose a
      timeline of the biological events and a tree diagram for risk calculation.
      CONCLUSIONS: Two profiles of cystic fibrosis patients can be envisaged: (1)
      patients with nonsevere mutation but low FEV1 baselines are becoming colonized
      with Af or (2) patients with high FEV1 baselines who present with severe mutation
      are more susceptible to the Af sensitization and then to the presentation of an
      allergic bronchopulmonary aspergillosis event.

PMID- 24336097
TI  - Mastalgia.

PMID- 24336098
TI  - NICE urged to recommend anastrozole for breast cancer prevention.

PMID- 24336100
TI  - Innate immunity: A surprise regulator of plasmacytoid DCs.

PMID- 24336099
TI  - Concepts of tissue injury and cell death in inflammation: a historical
      perspective.
AB  - Emerging evidence indicates that the molecular mechanisms of cell death have
      regulatory roles in inflammation and that the molecular changes that are
      associated with different forms of cell death affect the course of inflammation
      in different ways. In this Timeline article, we discuss how our understanding of
      the mechanisms and functional roles of tissue injury and cell death in
      inflammation has evolved on the basis of almost two centuries of study. We
      describe how such ideas have led to our current models of cell death and
      inflammation, and we highlight the remaining gaps in our knowledge of the
      subject.

PMID- 24336103
TI  - Immunometabolism: regulatory B cells weigh in.

PMID- 24336101
TI  - Human memory T cells: generation, compartmentalization and homeostasis.
AB  - Memory T cells constitute the most abundant lymphocyte population in the body for
      the majority of a person's lifetime; however, our understanding of memory T cell
      generation, function and maintenance mainly derives from mouse studies, which
      cannot recapitulate the exposure to multiple pathogens that occurs over many
      decades in humans. In this Review, we discuss studies focused on human memory T
      cells that reveal key properties of these cells, including subset heterogeneity
      and diverse tissue residence in multiple mucosal and lymphoid tissue sites. We
      also review how the function and the adaptability of human memory T cells depend
      on spatial and temporal compartmentalization. 

PMID- 24336104
TI  - Innate immunity: Making mice more human the TLR8 way.

PMID- 24336102
TI  - NOD proteins: regulators of inflammation in health and disease.
AB  - Entry of bacteria into host cells is an important virulence mechanism. Through
      peptidoglycan recognition, the nucleotide-binding oligomerization domain (NOD)
      proteins NOD1 and NOD2 enable detection of intracellular bacteria and promote
      their clearance through initiation of a pro-inflammatory transcriptional
      programme and other host defence pathways, including autophagy. Recent findings
      have expanded the scope of the cellular compartments monitored by NOD1 and NOD2
      and have elucidated the signalling pathways that are triggered downstream of NOD
      activation. In vivo, NOD1 and NOD2 have complex roles, both during bacterial
      infection and at homeostasis. The association of alleles that encode
      constitutively active or constitutively inactive forms of NOD2 with different
      diseases highlights this complexity and indicates that a balanced level of NOD
      signalling is crucial for the maintenance of immune homeostasis. 

PMID- 24336105
TI  - Macrophages: Early antifungal defence in kidneys.

PMID- 24336106
TI  - Tumour immunology: Anticancer drugs need bugs.

PMID- 24336107
TI  - Dampened regulates the activating potency of Bicoid and the embryonic patterning
      outcome in Drosophila.
AB  - The Drosophila morphogen gradient of Bicoid (Bcd) initiates anterior-posterior
      (AP) patterning; however, it is poorly understood how its ability to activate a
      target gene may have an impact on this process. Here we report an F-box protein,
      Dampened (Dmpd) as a nuclear cofactor of Bcd that can enhance its activating
      potency. We establish a quantitative platform to specifically investigate two
      parameters of a Bcd target gene response, expression amplitude and boundary
      position. We show that embryos lacking Dmpd have a reduced amplitude of Bcd
      activated hunchback (hb) expression at a critical time of development. This is
      because of a reduced Bcd-dependent transcribing probability. This defect is
      faithfully propagated further downstream of the AP-patterning network to alter
      the spatial characteristics of even-skipped (eve) stripes. Thus, unlike another
      Bcd-interacting F-box protein Fate-shifted (Fsd), which controls AP patterning
      through regulating the Bcd gradient profile, Dmpd achieves its patterning role
      through regulating the activating potency of Bcd. 

PMID- 24336109
TI  - Optimized production of biodiesel from waste cooking oil by lipase immobilized on
      magnetic nanoparticles.
AB  - Biodiesel, a non-toxic and biodegradable fuel, has recently become a major source
      of renewable alternative fuels. Utilization of lipase as a biocatalyst to produce
      biodiesel has advantages over common alkaline catalysts such as mild reaction
      conditions, easy product separation, and use of waste cooking oil as raw
      material. In this study, Pseudomonas cepacia lipase immobilized onto magnetic
      nanoparticles (MNP) was used for biodiesel production from waste cooking oil. The
      optimal dosage of lipase-bound MNP was 40% (w/w of oil) and there was little
      difference between stepwise addition of methanol at 12 h- and 24 h-intervals.
      Reaction temperature, substrate molar ratio (methanol/oil), and water content
      (w/w of oil) were optimized using response surface methodology (RSM). The optimal
      reaction conditions were 44.2  degrees C, substrate molar ratio of 5.2, and water
      content of 12.5%. The predicted and experimental molar conversions of fatty acid
      methyl esters (FAME) were 80% and 79%, respectively.

PMID- 24336108
TI  - Pericyte loss influences Alzheimer-like neurodegeneration in mice.
AB  - Pericytes are cells in the blood-brain barrier that degenerate in Alzheimer's
      disease (AD), a neurological disorder associated with neurovascular dysfunction,
      abnormal elevation of amyloid beta-peptide (Abeta), tau pathology and neuronal
      loss. Whether pericyte degeneration can influence AD-like neurodegeneration and
      contribute to disease pathogenesis remains, however, unknown. Here we show that
      in mice overexpressing Abeta-precursor protein, pericyte loss elevates brain
      Abeta40 and Abeta42 levels and accelerates amyloid angiopathy and cerebral beta
      amyloidosis by diminishing clearance of soluble Abeta40 and Abeta42 from brain
      interstitial fluid prior to Abeta deposition. We further show that pericyte
      deficiency leads to the development of tau pathology and an early neuronal loss
      that is normally absent in Abeta-precursor protein transgenic mice, resulting in
      cognitive decline. Our data suggest that pericytes control multiple steps of AD
      like neurodegeneration pathogenic cascade in Abeta-precursor protein
      overexpressing mice. Therefore, pericytes may represent a novel therapeutic
      target to modify disease progression in AD. 

PMID- 24336110
TI  - Radiation-sensitising effects of antennapedia proteins (ANTP)-SmacN7 on tumour
      cells.
AB  - The objective of this study was to investigate the underlying mechanisms behind
      the radiation-sensitising effects of the antennapedia proteins (ANTP)-smacN7
      fusion protein on tumour cells. ANTP-SmacN7 fusion proteins were synthesised, and
      the ability of this fusion protein to penetrate cells was observed. Effects of
      radiation on the expression of X-linked inhibitor of apoptosis protein (XIAP)
      were detected by western blotting. The radiation-sensitising effects of ANTP
      SmacN7 fusion proteins were observed by a clonogenic assay. The effects of drugs
      and radiation on tumour cell apoptosis were determined using Annexin V/FITC
      double staining. Changes in caspase-8, caspase-9 and caspase-3 were detected by
      western blot before and after ANTP-SmacN7 inhibition of XIAP. The ANTP-SmacN7
      fusion protein could enter and accumulate in cells; in vitro XIAP expression of
      radiation-induced tumour cells was negatively correlated with tumour
      radiosensitivity. The ANTP-SmacN7 fusion protein promoted tumour cell apoptosis
      through the activation of caspase3. ANTP-SmacN7 fusion protein may reduce tumour
      cell radioresistance by inducing caspase3 activation.

PMID- 24336111
TI  - MMP-7 and fcDNA serum levels in early NSCLC and idiopathic interstitial
      pneumonia: preliminary study.
AB  - A non-invasive test to facilitate the diagnosis of non-small cell lung cancer
      (NSCLC) and idiopathic pulmonary fibrosis (IPF) is still not available and
      represents an important goal. Forty-eight patients with stage I NSCLC, 45 with
      IPF, 30 with other idiopathic interstitial pneumonias (IIPs) including idiopathic
      non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity
      pneumonitis (HP), 35 with diffuse non-malignant disease and 30 healthy donors
      were enrolled onto the study. Free circulating (fc)DNA and MMP-7 levels were
      evaluated by Real Time PCR and ELISA, respectively. Median fcDNA levels were
      similar in NSCLC (127 ng/mL, range 23.6-345 ng/mL) and IPF (106 ng/mL, range 22
      224 ng/mL) patients, and significantly lower in IIPs patients, in individuals
      with other diseases and in healthy donors (p < 0.05). Conversely, median MMP-7
      values were significantly higher in IPF patients (9.10 ng/mL, range 3.88-19.72
      ng/mL) than in those with NSCLC (6.31 ng/mL, range 3.38-16.36 ng/mL; p < 0.0001),
      NSIP (6.50 ng/mL, range 1.50-22.47 ng/mL; p = 0.007), other diseases (5.41 ng/mL,
      range 1.78-15.91, p < 0.0001) or healthy donors (4.35 ng/mL, range 2.45-7.23; p <
      0.0001). Serum MMP-7 levels seem to be capable of distinguishing IPF patients
      from those with any other lung disease. fcDNA levels were similar in NSCLC and
      IPF patients, confirming its potential role as a biomarker, albeit non-specific,
      for the differential diagnosis of NSCLC.

PMID- 24336112
TI  - Phylogenetic relationships between four Salix L. species based on DArT markers.
AB  - The objectives of this study were to evaluate the usefulness of DArT markers in
      genotypic identification of willow species and describe genetic relationships
      between four willow species: Salix viminalis, S. purpurea, S. alba and S.
      triandra. The experimental plant material comprised 53 willow genotypes of these
      four species, which are popularly grown in Poland. DArT markers seem to identify
      Salix species with a high degree of accuracy. As a result, the examined species
      were divided into four distinct groups which corresponded to the four analyzed
      species. In our study, we observed that S. triandra was very different
      genetically from the other species, including S. alba which is generally
      classified into the same subgenus of Salix. The above corroborates the findings
      of other authors who relied on molecular methods to reveal that the
      classification of S. triandra to the subgenus Salix was erroneous. The Principal
      Coordinate Analysis (PCoA) and the neighbor-joining dendrogram also confirmed the
      clear division of the studied willow genotypes into four clusters corresponding
      to individual species. This confirmed the usefulness of DArT markers in taxonomic
      analyses and identification of willow species.

PMID- 24336113
TI  - Transcriptional activity of the FUT1 gene promoter region in pigs.
AB  - This study aims to provide a theoretical basis on the regulatory mechanism of the
      alpha-l,2-fucosyltransferase (FUT1) gene in pigs by analyzing the transcriptional
      activity of its promoter region. On the basis of the previously obtained promoter
      sequence, primers upstream and downstream of the gene were designed using the
      restriction endonucleases KpnI and HindIII respectively, and the recombinant
      plasmids of the pGL3-promoter were constructed by inserting promoter sequences
      with partially missing regions. The resultant mutants were observed by transient
      transfection assay into HEK293 cells, and the transcriptional activity of the
      promoter region was determined by luciferase activity. The 5'-flanking region of
      the FUT1 gene (-1150 to +50 bp) exhibited promoter activity. The -1150-bp to -849
      bp region showed negative regulation of the gene. The recombinant plasmid pGL3
      898 showed the strongest luciferase activity, and the activity showed a
      decreasing trend when the deleted region was increased. Recombinant plasmids were
      successfully constructed, verified, and the positive and negative regulation
      areas and core promoter region were detected, providing a deeper insight into the
      transcriptional regulatory mechanism of the FUT1 gene.

PMID- 24336114
TI  - S-phase kinase-associated protein 2 knockdown blocks colorectal cancer growth via
      regulation of both p27 and p16 expression.
AB  - The objective of this study was to determine the role and mechanism of S-phase
      kinase-associated protein 2 (Skp2) in colorectal cancer cell proliferation and
      survival both in vitro and in vivo. Adenoviral vector expressing Skp2 short
      hairpin RNA was transduced into SW480 cells. The effects of Skp2 on cell cycle
      and survival were assessed by Flow Cytometry. Cell proliferation was analyzed by
      MTT assay. The expression of cell cycle regulators p16 and p27 were measured by
      western blot. In vivo, human colorectal cancer was produced by xenograft of
      cancer cells in nude mouse. Tumor growth inhibitory rate was calculated to
      generate growth curve. Tumor growth was monitored by examining proliferating cell
      nuclear antigen expression, whereas tumor cell apoptosis was detected by TdT
      mediated dUTP nick-end labeling (TUNEL) staining. Knockdown of Skp2 blocked SW480
      tumor cell growth and induced cell apoptosis. Skp2 appeared to be very important
      for the progression of cell cycle at G1/S phase. In vivo, blockade of Skp2
      expression inhibited tumor growth and induced tumor apoptosis. Mechanistically,
      Skp2 regulated the expression of both p27 and p16 both in vitro and in vivo. The
      conclusion that we derive from this study is that Skp2 regulates colorectal
      cancer cell growth by inhibiting the expression of cell cycle regulator p27 and
      p16. 

PMID- 24336115
TI  - Clinical observation of 32P metabolic mode at the level of sub-target nuclides.
AB  - AIM: The aim of this paper was to observe the metabolic mode of 32P at the level
      of sub-target nuclides. METHODS: Twenty-one cancer patients were locally injected
      with 32P-labelled glass microspheres and then observed to determine the
      equalization of 32P radionuclide metabolism in the tumor target. We imaged 3 sub
      target regions of interest (ROI) 1/3 the size in both the anterior and posterior
      directions by bremsstrahlung single-photon emission computed tomography (SPECT) X
      ray imaging. The radiation dose parameters of the beta rays including the initial
      dose rate, the effective half-life, and the effective half-life of the cumulative
      radiation dose were then calculated. RESULTS: The radionuclide metabolism of the
      21 complete tumor targets complied with the mono-compartmental model of index
      metabolism, but the level of tumor control did not correlate with radiation dose
      parameters. In contrast, the radionuclide metabolism of the 63 sub-targets did
      not comply with the mono-compartmental model. Instead, 32 sub-targets were better
      represented by bi-compartmental or tri-compartmental metabolic models. None of
      the remaining 31 sub-targets complied with index metabolism. CONCLUSION: The
      complexity of the radiation dose at the sub-target level partially explains poor
      local tumor control. Future studies will be required to improve the expression of
      internal exposure to radiation dose parameters.

PMID- 24336116
TI  - Radiation protection study related to the future post-accelerator of the HIE
      ISOLDE project.
AB  - The HIE-ISOLDE project aims at expanding the physics programme of the ISOLDE
      facility at CERN. In particular, the addition of a superconducting linac will
      allow the post-acceleration of radioactive ion beams up to 10 MeV/u. However,
      because of field emission in the superconducting cavities and the possibility of
      neutron production for ion interactions above the Coulomb barrier, new
      radiological hazards need to be mitigated. Measurements of dose rate levels close
      to cavity prototypes were used to determine the intensity of the source of X ray
      due to field emission for a single cavity. The results were extrapolated to the
      operation of the 32 cavities that will be installed, and a detailed FLUKA
      calculation was performed to determine the required shielding to minimise the
      exposure of personnel present in the ISOLDE experimental hall during operation.
      FLUKA was also used to determine the maximum ambient dose equivalent rate levels
      in the accessible part of the hall due to ion beam losses for the envelope
      energies and intensities. 

PMID- 24336117
TI  - The system of radiation protection for neutrons: does it fit the purpose?
AB  - The present system of radiation protection for neutrons is reviewed with
      particular reference to the development of the protection quantities and their
      relationships with the operational quantities. Some of the shortcomings of the
      system are outlined, and the difficulties of measuring the operational
      quantities. Suggestions are made for future developments. 

PMID- 24336118
TI  - Comprehensive geriatric assessment and adjustment of cancer treatment.

PMID- 24336119
TI  - In reply.

PMID- 24336123
TI  - Addressing cancer disparities in Europe: a multifaceted problem that requires
      interdisciplinary solutions.

PMID- 24336124
TI  - The Prevalence of ADHD in a Population-Based Sample.
AB  - OBJECTIVE: Few studies of ADHD prevalence have used population-based samples,
      multiple informants, and Diagnostic and Statistical Manual of Mental Disorders
      (4th ed.; DSM-IV) criteria. Moreover, children who are asymptomatic while
      receiving ADHD medication often have been misclassified. Therefore, we conducted
      a population-based study to estimate the prevalence of ADHD in elementary school
      children using DSM-IV criteria. METHOD: We screened 7,587 children for ADHD.
      Teachers of 81% of the children completed a DSM-IV checklist. We then interviewed
      parents using a structured interview (DISC). Of these, 72% participated. Parent
      and teacher ratings were combined to determine ADHD status. We also estimated the
      proportion of cases attributable to other conditions. RESULTS: Overall, 15.5% of
      our sample met DSM- (4th ed.; text rev., DSM-IV-TR) criteria for ADHD (95% CI
      [14.6%, 16.4%]); 42% of cases reported no previous diagnosis. With additional
      information, other conditions explained 9% of cases. CONCLUSION: The prevalence
      of ADHD in this population-based sample was considerably higher than 3% to 7%. To
      compare study results, the DSM criteria need standardization.

PMID- 24336125
TI  - Chiral plasmonic DNA nanostructures with switchable circular dichroism.
AB  - Circular dichroism spectra of naturally occurring molecules and also of synthetic
      chiral arrangements of plasmonic particles often exhibit characteristic bisignate
      shapes. Such spectra consist of peaks next to dips (or vice versa) and result
      from the superposition of signals originating from many individual chiral objects
      oriented randomly in solution. Here we show that by first aligning and then
      toggling the orientation of DNA-origami-scaffolded nanoparticle helices attached
      to a substrate, we are able to reversibly switch the optical response between two
      distinct circular dichroism spectra corresponding to either perpendicular or
      parallel helix orientation with respect to the light beam. The observed
      directional circular dichroism of our switchable plasmonic material is in good
      agreement with predictions based on dipole approximation theory. Such dynamic
      metamaterials introduce functionality into soft matter-based optical devices and
      may enable novel data storage schemes or signal modulators. 

PMID- 24336126
TI  - GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome
      transient leukemia.
AB  - Transient leukemia (TL) is evident in 5-10% of all neonates with Down syndrome
      (DS) and associated with N-terminal truncating GATA1 mutations (GATA1s). Here we
      report that TL-cell clones generate abundant eosinophils in a substantial
      fraction of patients. Sorted eosinophils from patients with TL and eosinophilia
      carried the same GATA1s mutations as sorted TL blasts, consistent with their
      clonal origin. TL blasts exhibited a genetic program characteristic of
      eosinophils and differentiated along the eosinophil lineage in vitro. Similarly,
      ectopic expression of Gata1s, but not Gata1, in wild-type CD34(+)-hematopoietic
      stem and progenitor cells induced hyperproliferation of eosinophil promyelocytes
      in vitro. Although GATA1s retained the function of GATA1 to induce eosinophil
      genes by occupying their promoter regions, GATA1s was impaired in its ability to
      repress oncogenic MYC and the pro-proliferative E2F transcription network.
      Chromatin Immunoprecipitation Sequencing (ChIP-seq) indicated reduced GATA1s
      occupancy at the MYC promoter. Knockdown of MYC, or the obligate E2F-cooperation
      partner DP1, rescued the GATA1s-induced hyperproliferative phenotype. In
      agreement, terminal eosinophil maturation was blocked in Gata1(Deltae2) knockin
      mice, exclusively expressing Gata1s, leading to accumulation of eosinophil
      precursors in blood and bone marrow. These data suggest a direct relationship
      between the N-terminal truncating mutations of GATA1 and clonal eosinophilia in
      DS patients. 

PMID- 24336128
TI  - Determination of in vivo RNA structure in low-abundance transcripts.
AB  - RNA structure plays important roles in diverse biological processes. However, the
      structures of all but the few most abundant RNAs are presently unknown in vivo.
      Here we introduce DMS/SHAPE-LMPCR to query the in vivo structures of low
      abundance transcripts. DMS/SHAPE-LMPCR achieves attomole sensitivity, a 100,000
      fold improvement over conventional methods. We probe the structure of low
      abundance U12 small nuclear RNA (snRNA) in Arabidopsis thaliana and provide in
      vivo evidence supporting our derived phylogenetic structure. Interestingly, in
      contrast to mammalian U12 snRNAs, the loop of the SLIIb in U12 snRNA is variable
      among plant species, and DMS/SHAPE-LMPCR determines it to be unstructured. We
      reveal the effects of proteins on 25S rRNA, 5.8S rRNA and U12 snRNA structure,
      illustrating the critical importance of mapping RNA structure in vivo. Our
      universally applicable method opens the door to identifying and exploring the
      specific structure-function relationships of the multitude of low-abundance RNAs
      that prevail in living cells. 

PMID- 24336127
TI  - In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of
      adaptive immunity.
AB  - It remains unclear how the immune system affects leukemia development. To clarify
      the significance of the presence of immune systems in leukemia development, we
      transferred MLL/ENL leukemia cells into immune-competent or immune-deficient mice
      without any preconditioning including irradiation. The wild-type mice did not
      develop leukemia, whereas all the Rag2(-/-)gammac(-/-) mice lacking both adaptive
      immune cells and natural killer (NK) cells developed leukemia, indicating that
      leukemia cells were immunologically rejected. Interestingly, leukemia cells were
      also rejected in 60% of the Rag2(-/-) mice that lacked adaptive immune cells but
      possessed NK cells, suggesting that NK cells play a substantial role in the
      rejection of leukemia. Moreover, engraftment of leukemia cells was enhanced by NK
      cell depletion in Rag2(-/-) recipients and inhibited by transfer of NK cells into
      Rag2(-/-)gammac(-/-) recipients. Upregulation of NKG2D (NK group 2, member D)
      ligands in MLL/ENL leukemia cells caused elimination of leukemia cells by NK
      cells. Finally, we found that leukemia cells resistant to elimination by NK cells
      had been selected during leukemia development in Rag2(-/-) recipients. These
      results demonstrate that NK cells can eradicate MLL/ENL leukemia cells in vivo in
      the absence of adaptive immunity, thus suggesting that NK cells can play a potent
      role in immunosurveillance against leukemia. 

PMID- 24336129
TI  - Cytotoxic, cytostatic and HIV-1 PR inhibitory activities of the soft coral
      Litophyton arboreum.
AB  - Bioassay-guided fractionation using different chromatographic and spectroscopic
      techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to
      the isolation of nine compounds; sarcophytol M (1), alismol (2), 24
      methylcholesta-5,24(28)-diene-3beta-ol (3), 10-O-methyl alismoxide (4),
      alismoxide (5), (S)-chimyl alcohol (6), 7beta-acetoxy-24-methylcholesta-5-24(28)
      diene-3,19-diol (7), erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8), and
      24-methylcholesta-5,24 (28)-diene-3beta,7beta,19-triol (9). Some of the isolated
      compounds demonstrated potent cytotoxic- and/or cytostatic activity against HeLa
      and U937 cancer cell lines and inhibitory activity against HIV-1 protease (PR).
      Compound 7 was strongly cytotoxic against HeLa cells (CC50 4.3 +/- 0.75 uM), with
      selectivity index of SI 8.1, which was confirmed by real time cell electronic
      sensing (RT-CES). Compounds 2, 7, and 8 showed strong inhibitory activity against
      HIV-1 PR at IC50s of 7.20 +/- 0.7, 4.85 +/- 0.18, and 4.80 +/- 0.92 uM
      respectively. In silico docking of most compounds presented comparable scores to
      that of acetyl pepstatin, a known HIV-1 PR inhibitor. Interestingly, compound 8
      showed potent HIV-1 PR inhibitory activity in the absence of cytotoxicity against
      the cell lines used. In addition, compounds 2 and 5 demonstrated cytostatic
      action in HeLa cells, revealing potential use in virostatic cocktails. Taken
      together, data presented here suggest Litophyton arboreum to contain promising
      compounds for further investigation against the diseases mentioned.

PMID- 24336130
TI  - Three sudden cardiac deaths associated with Lyme carditis - United States,
      November 2012-July 2013.
AB  - Lyme disease is a multisystem illness caused by Borrelia burgdorferi, a
      spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000
      confirmed and probable cases of Lyme disease were reported in the United States
      in 2012, primarily from high-incidence states in the Northeast (Connecticut,
      Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York,
      Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and
      Wisconsin). Common manifestations include cutaneous, neurologic, and
      rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in
      recognized Lyme disease cases and usually resolves promptly with appropriate
      antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life
      threatening cardiac conduction abnormalities. During November 2012-July 2013, one
      woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme
      disease states experienced sudden cardiac death and, on postmortem examination,
      were found to have evidence of Lyme carditis. The three deaths were investigated
      by the Connecticut Department of Public Health, Massachusetts Department of
      Public Health, New Hampshire Department of Public Health, New York State
      Department of Health, and CDC. Donated corneas from two decedents had been
      transplanted to three recipients before the diagnosis of Lyme disease was
      established, but no evidence of disease transmission was found. Although death
      from Lyme carditis is rare, it should be considered in cases of sudden cardiac
      death in patients from high-incidence Lyme disease regions. Reducing exposure to
      ticks is the best method for preventing Lyme disease and other tickborne
      infections. 

PMID- 24336131
TI  - Estimated influenza illnesses and hospitalizations averted by influenza
      vaccination - United States, 2012-13 influenza season.
AB  - Influenza is associated with substantial morbidity and mortality each year in the
      United States. From 1976 to 2007, annual deaths from influenza ranged from
      approximately 3,300 to 49,000. Vaccination against influenza has been recommended
      to prevent illness and related complications, and since 2010, the Advisory
      Committee on Immunization Practices has recommended that all persons aged >=6
      months be vaccinated against influenza each year. In 2013, CDC published a model
      to quantify the annual number of influenza-associated illnesses and
      hospitalizations averted by influenza vaccination during the 2006-11 influenza
      seasons. Using that model with 2012-13 influenza season vaccination coverage
      rates, influenza vaccine effectiveness, and influenza hospitalization rates, CDC
      estimated that vaccination resulted in 79,000 (17%) fewer hospitalizations during
      the 2012-13 influenza season than otherwise might have occurred. Based on
      estimates of the percentage of influenza illnesses that involve hospitalization
      or medical attention, vaccination also prevented approximately 6.6 million
      influenza illnesses and 3.2 million medically attended illnesses. Influenza
      vaccination during the 2012-13 season produced a substantial reduction in
      influenza-associated illness. However, fewer than half of persons aged >=6 months
      were vaccinated. Higher vaccination rates would have resulted in prevention of a
      substantial number of additional cases and hospitalizations. 

PMID- 24336132
TI  - Seasonal influenza vaccination coverage among women who delivered a live-born
      infant - 21 states and New York City, 2009-10 and 2010-11 influenza seasons.
AB  - Because influenza can be especially severe during pregnancy, the American College
      of Obstetricians and Gynecologists and the Advisory Committee on Immunization
      Practices recommend influenza vaccination for pregnant women. Pregnant women
      experience increased morbidity from influenza infection, and they were at
      increased risk for severe disease and mortality from 2009 influenza A(H1N1) pdm09
      (pH1N1) pandemic virus infection. During the 2009-10 influenza season, CDC's
      Pregnancy Risk Assessment Monitoring System (PRAMS) began collecting data on
      pregnant women's vaccination coverage, and 22 areas continued to collect it
      during the 2010-11 season. To estimate state-specific seasonal influenza
      vaccination coverage among pregnant women for the 2010-11 influenza season, the
      most recent data available, CDC analyzed data from women who delivered a live
      born infant during September 2010-May 2011(N = 18,522). This report describes the
      results of that analysis, which indicated that, for the 2010-11 season, overall
      combined 53.6% were vaccinated (44.2% during pregnancy, 8.8% postpartum, and <1%
      with unknown time during pregnancy). Among those vaccinated during pregnancy,
      most were vaccinated during the second or third trimester. Wide state-to-state
      variation in vaccination coverage was observed, with a range of 32.6% to 75.9%
      and a median of 54.8%. Compared with the 2009-10 season, coverage was either the
      same or higher in all areas. Strategies that contributed to increased vaccination
      coverage need to be promoted. 

PMID- 24336133
TI  - Progress in immunization information systems - United States, 2012.
AB  - Immunization information systems (IIS) are confidential, computerized, population
      based systems that collect and consolidate vaccination data from vaccination
      providers that can be used in designing and sustaining effective immunization
      strategies. To monitor progress toward achieving IIS program goals, CDC annually
      surveys immunization program grantees using the IIS Annual Report (IISAR).
      Results from the 2012 IISAR, completed by 54 of 56 grantees, indicate that 86%
      (19.5 million) of U.S. children aged <6 years, and 25% (57.8 million) of U.S.
      adults participated in IIS. Eight of 12 minimum functional standards for IIS
      published by the National Vaccine Advisory Committee (NVAC) have been met by
      >=90% of grantees. During 2011-2012, progress was also made in meeting three
      additional functional standards, including the presence of core data element
      fields, timeliness of vaccine records, and Health Level 7 (HL7) messaging, and
      will be monitored in new functional standards for IIS published in 2013. Several
      new and ongoing initiatives, including interoperability between IIS and
      electronic health records (i.e., ensuring systems can work together and exchange
      information), the use of IIS to support vaccine ordering and inventory
      management, the use of two-dimensional barcodes to record vaccination
      information, and collaboration with pharmacies, federal agencies, and other adult
      vaccination providers, will support further progress in meeting functional
      standards and enhance reporting of adult vaccinations to IIS. 

PMID- 24336134
TI  - Progress toward poliomyelitis eradication - Nigeria, January 2012-September 2013.
AB  - Transmission of wild poliovirus (WPV) has never been interrupted in Afghanistan,
      Pakistan, and Nigeria, and since 2003, Nigeria has been a reservoir for WPV
      reintroduction to 25 polio-free countries. In 2012, the Nigerian government
      activated an emergency operations center and implemented a national emergency
      action plan to eradicate polio. The 2013 revision of this plan prioritized 1)
      improving quality of supplemental immunization activities (SIAs), 2) implementing
      strategies to reach underserved populations, 3) adopting special approaches in
      security-compromised areas, 4) improving outbreak response, 5) enhancing routine
      immunization and activities implemented between SIAs, and 6) strengthening
      surveillance. This report summarizes polio eradication activities in Nigeria
      during January 2012-September 2013 and updates previous reports. During January
      September 2013, 49 polio cases were reported from 26 local government areas
      (LGAs) in nine states in Nigeria, compared with 101 cases reported from 70 LGAs
      in 13 states during the same period in 2012. For all of 2012, a total of 122
      cases were reported. No WPV type 3 (WPV3) cases have been reported since November
      2012. For the first time ever, in 2013, no polio cases of any type have been
      detected in the northwest of Nigeria; however, transmission continues in Kano and
      states in the northeast. Despite considerable progress, 24 LGAs in 2012 and seven
      LGAs in 2013 reported two or more cases; WPV continues to circulate in eight LGAs
      that had cases in 2012. Efforts to interrupt transmission remain impeded by
      insecurity, anti-polio-vaccine sentiment, and chronically poor SIA implementation
      in selected areas. Improvement of SIA quality and effective outbreak response
      will be needed to interrupt WPV transmission in 2014. 

PMID- 24336135
TI  - Extent and effects of recurrent shortages of purified-protein derivative
      tuberculin skin test antigen solutions - United States, 2013.
AB  - Two purified-protein derivative (PPD) tuberculin skin test (TST) antigen
      solutions are approved by the U.S. Food and Drug Administration (FDA): Tubersol
      (Sanofi Pasteur Limited) and Aplisol (JHP Pharmaceuticals, LLC). Tubersol was out
      of production in late 2012 through April 2013. Shortages of Aplisol have resulted
      from increased demand as practitioners have sought a substitute for Tubersol.
      Tubersol production resumed in May 2013, and supplies had been nearly restored by
      early June. However, in mid-July, state tuberculosis (TB) control officials
      notified CDC of difficulty obtaining Tubersol and Aplisol. Sanofi Pasteur
      notified FDA of a temporary delay in the availability of tuberculin in the 10
      dose and 50-dose presentations. In mid-October, the 10-dose presentation was
      being returned to market, on allocation, which means that historical purchasing
      practices determine the amount that customers are allotted. In late October, the
      50-dose presentation was being returned to market, also on allocation, one vial
      per historical customer per month. Supplies are forecast to approach normal
      during January 2014, after distributors have restored their supply chains. A
      compensatory surge in testing after deferment of testing during the periods of
      shortage might cause further temporary instability of supplies. In mid-August
      2013, officials in 29 of 52 U.S. jurisdictions noted a shortage of at least one
      PPD TST antigen solution in health departments to the extent that it interrupted
      activities. This report includes a summary of the extent and effects of the
      shortages and a reiteration of advice on how to adapt to them. 

PMID- 24336136
TI  - Notes from the field: severe illness associated with reported use of synthetic
      marijuana - Colorado, August-September 2013.
AB  - On August 30, 2013, the Colorado Department of Public Health and Environment
      (CDPHE) was notified by several hospitals of an increase in the number of
      patients visiting their emergency departments (EDs) with altered mental status
      after using synthetic marijuana. Synthetic marijuana is dried plant material
      sprayed with various synthetic cannabinoids and smoked as an alternative to
      smoking marijuana. In response to the increase in ED visits associated with the
      use of synthetic marijuana, CDPHE asked all Colorado EDs to report through
      EMResource (a web-based reporting system) any patients examined on or after
      August 21 with altered mental status after use of a synthetic marijuana product.
      Serum and urine specimens from patients also were requested. On September 8,
      CDPHE, with the assistance of CDC, began an epidemiologic investigation to
      characterize the outbreak, determine the active substance and source of the
      synthetic marijuana product, and prevent further morbidity and mortality.
      Investigators reviewed ED visit reports submitted through EMResource and medical
      charts. A probable case was defined as any illness resulting in a visit to a
      Colorado ED during August 21-September 18, 2013, by a patient with suspected
      synthetic marijuana use in the 24 hours preceding illness onset. Of 263 patient
      visits reported to CDPHE through EMResource (214) and other means, such as e-mail
      and fax (49), a total of 221 (84%) represented probable cases (Figure). 

PMID- 24336137
TI  - Improving the assessment of heart toxicity for all new drugs through
      translational regulatory science.
AB  - Fourteen drugs have been removed from the market worldwide because they cause
      torsade de pointes. Most drugs that cause torsade can be identified by assessing
      whether they block the human ether a gogo related gene (hERG) potassium channel
      and prolong the QT interval on the electrocardiogram. In response, regulatory
      agencies require new drugs to undergo "thorough QT" studies. However, some drugs
      block hERG potassium channels and prolong QT with minimal torsade risk because
      they also block calcium and/or sodium channels. Through analysis of clinical and
      preclinical data from 34 studies submitted to the US Food and Drug Administration
      and by computer simulations, we demonstrate that by dividing the QT interval into
      its components of depolarization (QRS), early repolarization (J-Tpeak), and late
      repolarization (Tpeak-Tend), along with atrioventricular conduction delay (PR),
      it may be possible to determine which hERG potassium channel blockers also have
      calcium and/or sodium channel blocking activity. This translational regulatory
      science approach may enable innovative drugs that otherwise would have been
      labeled unsafe to come to market. 

PMID- 24336138
TI  - Disparities in deep brain stimulation surgery among insured elders with Parkinson
      disease.
AB  - OBJECTIVE: To identify sociodemographic, clinical, and physician/practice factors
      associated with deep brain stimulation (DBS). DBS is a proven surgical therapy
      for Parkinson disease (PD), but is recommended only for patients with excellent
      health, results in significant out-of-pocket costs, and requires substantial
      physician involvement. METHODS: Retrospective cohort study of more than 657,000
      Medicare beneficiaries with PD. Multivariable logistic regression models examined
      the association between demographic, clinical, socioeconomic status (SES), and
      physician/practice factors, and DBS therapy. RESULTS: There were significant
      disparities in the use of DBS therapy among Medicare beneficiaries with PD. The
      greatest disparities were associated with race: black (adjusted odds ratio [AOR]
      0.20, 95% confidence interval [CI] 0.16-0.25) and Asian (AOR 0.55, 95% CI 0.44
      0.70) beneficiaries were considerably less likely to receive DBS than white
      beneficiaries. Women (AOR 0.79, 95% CI 0.75-0.83) also had lower odds of
      receiving DBS compared with men. Eighteen percent of procedures were performed on
      patients with PD who had cognitive impairment/dementia, a reported
      contraindication to DBS. Beneficiaries treated in minority-serving PD practices
      were less likely to receive DBS, regardless of individual race (AOR 0.76, 95% CI
      0.66-0.87). Even after adjustment for demographic and clinical covariates, high
      neighborhood SES was associated with 1.4-fold higher odds of receiving DBS (AOR
      1.42, 95% CI 1.33-1.53). CONCLUSIONS: Among elderly Medicare beneficiaries with
      PD, race, sex, and neighborhood SES are strong independent predictors of DBS
      receipt. Racial disparities are amplified when adjusting for physician/clinic
      characteristics. Future investigations of the demographic differences in clinical
      need/usefulness of DBS, ease of DBS attainment, and actual/opportunity DBS costs
      are needed to inform policies to reduce DBS disparities and improve PD quality of
      care.

PMID- 24336139
TI  - Is there a link between gynecologic surgeries and Alzheimer disease?

PMID- 24336140
TI  - Neuropsychiatric changes precede classic motor symptoms in ALS and do not affect
      survival.
AB  - OBJECTIVES: To investigate patient susceptibility to neuropsychiatric symptoms in
      the context of progression of more classic motor symptoms in amyotrophic lateral
      sclerosis (ALS) and to examine the impact of neuropsychiatric symptoms on
      survival. METHODS: The study cohort consisted of 219 patients with ALS (limb
      onset = 159; bulbar onset = 60), with neuropsychiatric symptoms measured using
      the Motor Neuron Disease Behavioural Scale and more classic ALS symptoms assessed
      by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. For
      detection of symptom susceptibility (neuropsychiatric vs classic motor), a Rasch
      analysis was applied (n = 219). Cox proportional hazard regression models were
      used for the survival analysis (n = 115 patients), which incorporated
      neuropsychiatric and classic motor symptoms. RESULTS: Rasch analysis demonstrated
      that neuropsychiatric symptoms appeared earlier than classic motor features of
      ALS. However, differences in neuropsychiatric scores did not affect survival:
      patients with abnormalities in neuropsychiatric domains did not exhibit a
      different rate of survival than those without (chi(2), 3.447, p = 0.328, -2 log
      likelihood 377.341). CONCLUSIONS: Neuropsychiatric symptoms appear before classic
      motor features in ALS, which corroborates the notion that ALS and frontotemporal
      dementia lie on a disease continuum. The early detection of neuropsychiatric
      symptoms will be critical to inform clinical decisions and alleviate carer
      burden. Importantly, subtle neuropsychiatric symptoms alone do not affect
      survival in ALS, which in turn confirms their pervasive nature in ALS.

PMID- 24336141
TI  - Age at surgical menopause influences cognitive decline and Alzheimer pathology in
      older women.
AB  - OBJECTIVE: To determine the association between age at surgical menopause and
      both cognitive decline and Alzheimer disease (AD) pathology in 2 longitudinal
      cohorts. METHODS: Female subjects from 2 longitudinal studies of cognitive
      decline (Religious Orders Study and Rush Memory and Aging Project) were included
      (total n = 1,884). The primary analysis examined the association between age at
      surgical menopause and decline in a global cognition score. Secondary analyses
      examined additional outcomes: 1) decline in 5 cognitive subdomains and 2) a
      global measure of the burden of AD pathology. In exploratory analyses, we
      examined the effect of hormone replacement therapy (HRT). We adjusted all models
      for age, education, smoking, and cohort and stratified by surgical vs natural
      menopause. RESULTS: For the 32% of subjects with surgical menopause, earlier age
      at menopause was associated with faster decline in global cognition (p = 0.0007),
      specifically episodic memory (p = 0.0003) and semantic memory (p = 0.002).
      Earlier age at menopause was also associated with increased AD neuropathology (p
      = 0.038), in particular neuritic plaques (p = 0.013). HRT use for at least 10
      years, when administered within a 5-year perimenopausal window, was associated
      with decreased decline in global cognition. No associations were seen in women
      who had natural menopause. CONCLUSIONS: Early age at surgical menopause was
      associated with cognitive decline and AD neuropathology. Ongoing studies should
      clarify the potential effect of HRT on this relationship.

PMID- 24336142
TI  - Ficolin-3-mediated lectin complement pathway activation in patients with
      subarachnoid hemorrhage.
AB  - OBJECTIVES: To assess the involvement of ficolin-3, the main initiator of the
      lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and
      outcome. METHODS: In this preliminary exploratory study, plasma concentration of
      ficolin-3 and of ficolin-3-mediated functional LCP activity was measured, along
      with that of other LCP initiators (mannose-binding lectin, ficolin-2, and ficolin
      1), C3 activation products, and soluble C5b-9 terminal complex, in a prospective
      cohort of 39 patients with SAH and 20 healthy controls. The following parameters
      were recorded: SAH severity, assessed using the World Federation of Neurosurgical
      Societies grading scale; vasospasm, defined as neuro-worsening with angiographic
      confirmation of vessel narrowing; cerebral ischemia, defined as hypodense lesion
      on CT scan performed before discharge; and 6-month outcome, assessed using the
      Glasgow Outcome Scale. RESULTS: In patients, no changes were detected for ficolin
      3 compared with controls. Notably, however, ficolin-3-mediated functional LCP
      activity was reduced. Low levels of plasma ficolin-3 and ficolin-3-mediated
      functional LCP activity were related to SAH severity, vasospasm, and cerebral
      ischemia. Moreover, ficolin-3 functional LCP activity was decreased in patients
      with unfavorable outcome. CONCLUSION: Our data provide evidence that LCP is
      activated after SAH and that the actual plasma concentrations of ficolin-3
      reflect the severity of brain injury as evaluated by clinical and structural
      parameters. These results support the idea that ficolin-3-mediated functional LCP
      activity may be targeted to control injury progression in SAH.

PMID- 24336143
TI  - Effect of head impacts on diffusivity measures in a cohort of collegiate contact
      sport athletes.
AB  - OBJECTIVE: To determine whether exposure to repetitive head impacts over a single
      season affects white matter diffusion measures in collegiate contact sport
      athletes. METHODS: A prospective cohort study at a Division I NCAA athletic
      program of 80 nonconcussed varsity football and ice hockey players who wore
      instrumented helmets that recorded the acceleration-time history of the head
      following impact, and 79 non-contact sport athletes. Assessment occurred
      preseason and shortly after the season with diffusion tensor imaging and
      neurocognitive measures. RESULTS: There was a significant (p = 0.011) athlete
      group difference for mean diffusivity (MD) in the corpus callosum. Postseason
      fractional anisotropy (FA) differed (p = 0.001) in the amygdala (0.238 vs 0.233).
      Measures of head impact exposure correlated with white matter diffusivity
      measures in several brain regions, including the corpus callosum, amygdala,
      cerebellar white matter, hippocampus, and thalamus. The magnitude of change in
      corpus callosum MD postseason was associated with poorer performance on a measure
      of verbal learning and memory. CONCLUSION: This study suggests a relationship
      between head impact exposure, white matter diffusion measures, and cognition over
      the course of a single season, even in the absence of diagnosed concussion, in a
      cohort of college athletes. Further work is needed to assess whether such effects
      are short term or persistent.

PMID- 24336144
TI  - Assessing treatment response to interferon-beta: is there a role for MRI?
AB  - OBJECTIVE: Interferon-beta (IFN-beta) has been shown to reduce relapse rates in
      multiple sclerosis; however, the clinical response appears to vary among
      individuals. Can early MRI be used to identify those patients who have a poor
      response to treatment? METHODS: A systematic review of studies examining
      differential treatment response and clinical endpoints in groups defined as
      responders or nonresponders to IFN-beta was performed. Meta-analytic techniques
      were used to combine study results where appropriate. RESULTS: Patients with MRI
      evidence of poor response to IFN-beta treatment as defined by either >=2 new
      hyperintense T2 lesions or new gadolinium-enhancing lesions had significantly
      increased risk of both future relapses and progression as defined by the Expanded
      Disability Status Scale. There appeared to be an increased risk of poor outcomes
      16 years after treatment initiation in those with an initial poor response to
      treatment. Previous evidence has shown this not to be the case in placebo arms of
      clinical trials. CONCLUSIONS: For those patients starting IFN-beta, early MRI,
      within 6 to 24 months after starting treatment, has the potential to provide
      important information when counseling patients about the likelihood of future
      treatment failure. This can inform treatment decisions before clinical relapses
      or disease progression.

PMID- 24336145
TI  - Spherical, cylindrical and tetrahedral symmetries; hydrogenic states at high
      magnetic field in Si:P.
AB  - Phosphorous donors in silicon have an electronic structure that mimics the
      hydrogen atom, albeit on a larger length, smaller energy and smaller magnetic
      field scale. While the hydrogen atom is spherically symmetric, an applied
      magnetic field imposes cylindrical symmetry, and the solid-state analogue
      involves, in addition, the symmetry of the Si crystal. For one magnetic field
      direction, all six conduction-band valleys of Si:P become equivalent. New
      experimental data to high laboratory fields (30 T), supported by new
      calculations, demonstrate that this high symmetry field orientation allows the
      most direct comparison with free hydrogen. 

PMID- 24336146
TI  - forqs: forward-in-time simulation of recombination, quantitative traits and
      selection.
AB  - SUMMARY: forqs is a forward-in-time simulation of recombination, quantitative
      traits and selection. It was designed to investigate haplotype patterns resulting
      from scenarios where substantial evolutionary change has taken place in a small
      number of generations due to recombination and/or selection on polygenic
      quantitative traits. AVAILABILITY AND IMPLEMENTATION: forqs is implemented as a
      command-line C++ program. Source code and binary executables for Linux, OSX and
      Windows are freely available under a permissive BSD license:
      https://bitbucket.org/dkessner/forqs.

PMID- 24336147
TI  - Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime (BAT
      L) clinical interview and the VA TBI screen.
AB  - OBJECTIVE: Mild traumatic brain injury is the signature injury of Operation
      Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn
      (OND), yet its identification and diagnosis is controversial and fraught with
      challenges. SETTING: In 2007, the Department of Veterans Affairs (VA) implemented
      a policy requiring traumatic brain injury (TBI) screening on all individuals
      returning from deployment in the OEF/OIF/OND theaters of operation that lead to
      the rapid and widespread use of the VA TBI screen. The Boston Assessment of TBI
      Lifetime (BAT-L) is the first validated, postcombat semistructured clinical
      interview to characterize head injuries and diagnose TBIs throughout the life
      span, including prior to, during, and post-military service. PARTICIPANTS:
      Community-dwelling convenience sample of 179 OEF/OIF/OND veterans. MAIN MEASURES:
      BAT-L, VA TBI screen. RESULTS: Based on BAT-L diagnosis of military TBI, the VA
      TBI screen demonstrated similar sensitivity (0.85) and specificity (0.82) when
      administered by research staff. When BAT-L diagnosis was compared with historical
      clinician-administered VA TBI screen in a subset of participants, sensitivity was
      reduced. CONCLUSIONS: The specificity of the research-administered VA TBI screen
      was more than adequate. The sensitivity of the VA TBI screen, although relatively
      high, suggests that it does not oversample or "catch all" possible military TBIs.
      Traumatic brain injuries identified by the BAT-L, but not identified by the VA
      TBI screen, were predominantly noncombat military injuries. There is potential
      concern regarding the validity and reliability of the clinician administered VA
      TBI screen, as we found poor correspondence between it and the BAT-L, as well as
      low interrater reliability between the clinician-administered and research
      administered screen.

PMID- 24336148
TI  - Coated-platelet levels are persistently elevated in patients with mild traumatic
      brain injury.
AB  - OBJECTIVE: Coated-platelets are procoagulant platelets that are elevated in
      patients with large-vessel ischemic stroke and are associated with stroke
      recurrence. Because of recent reports showing an increased risk for stroke
      following traumatic brain injury (TBI), we undertook a pilot study to investigate
      coated-platelet synthesis in veterans with TBI. DESIGN: Cross-sectional study.
      PARTICIPANTS: Forty patients with a diagnosis of mild TBI (mTBI) and 40 controls
      without a history of TBI and matched for age, gender, and ethnicity/race were
      enrolled in the study. MAIN MEASURE: Coated-platelet levels were determined in
      patients with mTBI and controls. The time period since most recent injury ranged
      from 6 months to 9 years. RESULTS: Coated-platelet levels were significantly
      higher for mTBI patients than for controls (mean +/- SD = 52.0% +/- 14.0% vs
      35.4% +/- 13.0%; P < .0001). No relationship between these levels and the length
      of time since the last injury was found (P = .5). CONCLUSIONS: Coated-platelet
      levels are markedly and persistently elevated in individuals with mTBI. These
      data suggest a link to previous findings of increased stroke risk and chronic
      inflammation among individuals who sustained a TBI.

PMID- 24336149
TI  - Bacterial physiology: remodelling the FtsZ network.

PMID- 24336150
TI  - CaMKII phosphorylation of neuroligin-1 regulates excitatory synapses.
AB  - Neuroligins are postsynaptic cell adhesion molecules that are important for
      synaptic function through their trans-synaptic interaction with neurexins
      (NRXNs). The localization and synaptic effects of neuroligin-1 (NL-1, also called
      NLGN1) are specific to excitatory synapses with the capacity to enhance
      excitatory synapses dependent on synaptic activity or Ca(2+)/calmodulin kinase II
      (CaMKII). Here we report that CaMKII robustly phosphorylates the intracellular
      domain of NL-1. We show that T739 is the dominant CaMKII site on NL-1 and is
      phosphorylated in response to synaptic activity in cultured rodent neurons and
      sensory experience in vivo. Furthermore, a phosphodeficient mutant (NL-1 T739A)
      reduces the basal and activity-driven surface expression of NL-1, leading to a
      reduction in neuroligin-mediated excitatory synaptic potentiation. To the best of
      our knowledge, our results are the first to demonstrate a direct functional
      interaction between CaMKII and NL-1, two primary components of excitatory
      synapses. 

PMID- 24336151
TI  - Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.
AB  - The formation and recall of episodic memory requires precise information
      processing by the entorhinal-hippocampal network. For several decades, the
      trisynaptic circuit entorhinal cortex layer II (ECII)->dentate gyrus->CA3->CA1
      and the monosynaptic circuit ECIII->CA1 have been considered the primary
      substrates of the network responsible for learning and memory. Circuits linked to
      another hippocampal region, CA2, have only recently come to light. Using highly
      cell type-specific transgenic mouse lines, optogenetics and patch-clamp
      recordings, we found that dentate gyrus cells, long believed to not project to
      CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant
      longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic
      circuit, but, unlike CA3, projected preferentially to the deep, rather than to
      the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge,
      ECIII did not project to CA2. Our results allow a deeper understanding of the
      biology of learning and memory. 

PMID- 24336152
TI  - Optical investigation of the natural electron doping in thin MoS2 films deposited
      on dielectric substrates.
AB  - Two-dimensional (2D) compounds provide unique building blocks for novel layered
      devices and hybrid photonic structures. However, large surface-to-volume ratio in
      thin films enhances the significance of surface interactions and charging effects
      requiring new understanding. Here we use micro-photoluminescence (PL) and
      ultrasonic force microscopy to explore the influence of the dielectric
      environment on optical properties of a few monolayer MoS2 films. PL spectra for
      MoS2 films deposited on SiO2 substrates are found to vary widely. This film-to
      film variation is suppressed by additional capping of MoS2 with SiO2 and
      Si(x)N(y), improving mechanical coupling of MoS2 with surrounding dielectrics. We
      show that the observed PL non-uniformities are related to strong variation in the
      local electron charging of MoS2 films. In completely encapsulated films, negative
      charging is enhanced leading to uniform optical properties. Observed great
      sensitivity of optical characteristics of 2D films to surface interactions has
      important implications for optoelectronics applications of layered materials.

PMID- 24336153
TI  - One-pot microbial method to synthesize dual-doped graphene and its use as high
      performance electrocatalyst.
AB  - A novel strategy to synthesize nitrogen (N) and sulfur (S)-doped graphene (G) is
      developed through sulfate-reducing bacteria treating graphene oxide (GO). The N,
      S-doped G demonstrates significantly improved electrocatalytic properties and
      electrochemical sensing performances in comparison with single-doped graphene due
      to the synergistic effects of dual dopants on the properties of graphene. 

PMID- 24336154
TI  - Lack of presence of the human cytomegalovirus in human glioblastoma.
AB  - Recent reports have indicated human cytomegalovirus (HCMV) to be associated with
      human glioblastoma carcinogenesis. In established examples of viral
      carcinogenesis, viral DNA and one or more of its products have been detected in
      most tumor cells of biopsies in the majority of cases. To test whether HCMV is
      associated with human glioblastoma based on this criterion, we measured the
      number of viral DNA molecules per cell in both frozen and paraffin-embedded tumor
      biopsies from 58 patients using real-time quantitative PCR (QPCR).
      Immunohistochemical and fluorescence in situ hybridization (FISH) to detect HCMV
      proteins and genome was performed in 10 cases using formalin-fixed paraffin
      embedded glioblastoma tissues. Southern blotting using DNA extracted from four
      glioblastoma cell lines together with immunoblotting using the four cell lines
      and five glioblastoma tissue samples were also performed. We further confirmed
      the immunoblot bands using liquid chromatography-tandem mass spectrometry assay.
      As a result, HCMV DNA was not detected in the tumor cells from any of the
      glioblastoma cases by QPCR detecting two different HCMV genes, in clear contrast
      to samples from patients with HCMV infection. Southern blotting and
      immunoblotting of cell lines and FISH using paraffin sections were all negative.
      However, immunoblotting and immunohistochemistry using tissue samples were partly
      positive, but HCMV proteins were not detected by proteomic analysis, suggesting
      false positivity of the analyses. As our QPCR analysis could detect 10 copies of
      HCMV DNA mixed with DNA extracted from 10(4) HCMV-negative cells, we conclude
      that HCMV is not persistent, at least in the tumor cells, of developed human
      glioblastoma.

PMID- 24336155
TI  - Utilization of cell-transferred cytologic smears in detection of EGFR and KRAS
      mutation on adenocarcinoma of lung.
AB  - Cell-transfer technique has been proven useful for performing immunocytochemistry
      on fine-needle aspiration smears. However, its utility for EGFR and KRAS
      molecular testing has not been validated. Molecular testing was performed using
      the cell-transfer technique on both Papanicolaou-stained ethanol-fixed and Hema 3
      stained air-dried smears from 32 fine-needle aspiration samples that had
      diagnoses of adenocarcinoma of the lung, and then was compared to the results of
      the corresponding formalin-fixed paraffin-embedded tissues. The molecular testing
      was successfully performed on 32 of 32 ethanol-fixed and 31 of 32 air-dried
      samples. The molecular results on ethanol-fixed and air-dried smears showed 100%
      agreement. There is 100% (32/32) agreement for the EGFR and 97% (31/32) agreement
      for the KRAS between the cell-transfer technique and formalin-fixed paraffin
      embedded tissues. One discrepant case was due to low percentage of tumor cells on
      the smears. Cell-transfer technique is a reliable alternative method for EGFR and
      KRAS testing if the cell blocks lack adequate cellularity. 

PMID- 24336156
TI  - Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell
      lymphoma patients treated with rituximab-CHOP.
AB  - In order to address the debatable prognostic role of MYC rearrangements in
      diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide,
      hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements
      by fluorescence in situ hybridization in 563 cases using break-apart probes and
      IGH/MYC dual-fusion probes. Concurrent BCL2 and BCL6 aberrations were also
      assessed. Data were correlated with clinicopathological variables and prognostic
      parameters. MYC rearrangements were observed in 39/432 evaluable cases (9%),
      including 4 rearrangements detectable only with the dual-fusion probes, 15
      detectable only with the break-apart probes and 20 detectable with both dual
      fusion probes and break-apart probes. MYC rearrangements correlated with germinal
      center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor
      mass size (P=0.0003). Patients with MYC rearrangements were more likely to be
      treatment resistant (P<0.0001). All types of MYC rearrangements were associated
      with poorer disease-specific survival, that is, 20/39 dead, median disease
      specific survival 42 months, compared with 98/393 dead among the non-rearranged
      cases, median disease-specific survival not reached (P=0.0002). Cases with MYC
      rearrangements that overexpressed MYC protein were at risk with respect to
      disease-specific survival independent of the International Prognostic Index
      (P=0.046 and P<0.001, respectively). Presence of concurrent BCL2 aberrations but
      not of BCL6 aberrations was prognostically additive. Radiotherapy seemed to
      diminish the prognostic effects of MYC rearrangements in diffuse large B-cell
      lymphoma patients since only 2/10 irradiated patients with MYC rearrangements
      died of/with disease, compared with 16/28 non-irradiated patients with MYC
      rearrangements. We conclude that MYC rearrangements add prognostic information
      for individual risk estimation and such cases might represent a distinct,
      biologically determined disease subgroup.

PMID- 24336157
TI  - Retinoblastoma pathway deregulatory mechanisms determine clinical outcome in high
      grade serous ovarian carcinoma.
AB  - Alterations in the retinoblastoma pathway are frequent in ovarian/tubal high
      grade serous cancers, but the mechanism of deregulation and the impact on patient
      outcome are poorly understood. A cohort of 334 high-grade serous carcinomas was
      studied by immunohistochemical analysis of RB1, p16, cyclin D1, cyclin E1, and
      Ki67. Additional detailed analyses including RB1 allelic deletion (n=42),
      mutation (n=75), methylation (n=31), and SNP array analyses (n=75) were performed
      on cases with clinical parameters, including age, debulking status, treatment,
      and clinical outcome. p16/RB1 expression results yielded three distinct
      clinically relevant subgroups upon multivariable analysis controlling for stage,
      debulking status, and treatment types: p16 homogeneous/RB1+ with the shortest
      progression-free survival (median 15 months (95% CI: 13-18); P=0.016) compared
      with the p16 heterogeneous/RB1+ subgroup (median 22 months (95% CI: 16-32)) and
      the p16 homogeneous/RB1- subgroup (median 20 months (95% CI: 15-24)). Patients in
      the p16 homo/RB1- subgroup showed a significant increase in overall survival (>60
      months; P=0.013), which suggests an increase in sensitivity to cytotoxic agents.
      Analyses of Rb pathway mechanistic differences among these groups revealed
      frequent RB1 genomic alterations such as RB1 allelic loss and/or large spanning
      deletions (83%) in the p16 homo/RB1- subgroups, also indicating that RB1
      deletions are frequent in high-grade serous carcinoma. CCNE1 gene
      gains/amplifications were frequent in the p16 homogeneous/RB1+ subgroup (68%) and
      cyclin D1 protein overexpression was predominantly characteristic of the p16
      heterogeneous/RB1+ subgroup. These subcategories occur early in tumor progression
      and are seen with similar frequency in the cancer precursor lesion, serous tubal
      intra-epithelial carcinoma. Overall, this study uniquely identifies multiple non
      synonymous mechanisms of retinoblastoma pathway deregulation that correlate with
      significantly different clinical outcomes. Furthermore, deregulations identified
      in precursor lesions suggest a key role of this pathway in serous tumor
      development. Recognition of these categories may identify patients with increased
      sensitivity to chemotherapy and new opportunities for novel therapeutics.

PMID- 24336158
TI  - Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations
      and ZNF217 amplification in ovarian clear cell carcinoma.
AB  - AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non
      fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene,
      phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc-finger
      protein 217 (ZNF217) gene have been identified as frequent molecular genetic
      changes in ovarian clear cell carcinoma. The relationships between these events
      have not been studied and integrated in the same cohort. This study was aimed at
      determining the correlation between these molecular events and other
      clinicopathological factors, including the prognostic impacts of these
      clinicopathological factors. A total of 68 ovarian clear cell carcinoma cases
      were collected and subjected to immunohistochemistry testing for ARID1A, SMARCA2,
      SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for
      phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)
      gene and fluorescence in situ hybridization for ZNF217 amplification. The
      correlations between ARID1A expression, PI3K-Akt pathway, ZNF217 amplification
      and other clinicopathological factors were analyzed. Loss of ARID1A expression
      was present in 35 cases (52%) and loss of SMARCA2 expression occurred in 1 case.
      SMARCA4 and SMARCB1 expressions were preserved in all cases. PIK3CA mutations
      were present in 23 cases (34%) and loss of PTEN expression occurred in 8 cases
      (12%). Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN
      expression) were found in 42 cases (62%). ZNF217 amplification was detected in 21
      cases (31%). Loss of ARID1A expression was significantly related to younger
      patient age (P=0.048), PI3K-Akt pathway activation (P=0.046) and ZNF217
      amplification (P=0.028). All of the clinicopathological factors were not
      prognostic factors for ovarian clear cell carcinoma after multivariate analysis,
      except International Federation of Gynecology and Obstetrics staging (P=0.001).
      Our results showed that loss of ARID1A expression usually coexisted with PI3K-Akt
      pathway activation and/or ZNF217 amplification. Synergic effects of loss of
      ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be
      related to the development of ovarian clear cell carcinoma.

PMID- 24336159
TI  - Signatures of the electronic nature of pairing in high-T(c) superconductors
      obtained by non-equilibrium boson spectroscopy.
AB  - Understanding the pairing mechanism that gives rise to high-temperature
      superconductivity is one of the longest-standing problems of condensed-matter
      physics. Almost three decades after its discovery, even the question of whether
      or not phonons are involved remains a point of contention to some. Here we
      describe a technique for determining the spectra of bosons generated during the
      formation of Cooper pairs on recombination of hot electrons as they tunnel
      between the layers of a cuprate superconductor. The results obtained indicate
      that the bosons that mediate pairing decay over micrometre-scale distances and
      picosecond timescales, implying that they propagate at a speed of around 106 m s
      1. This value is more than two orders of magnitude greater than the phonon
      propagation speed but close to Fermi velocity for electrons, suggesting that the
      pairing mechanism is mediated by unconventional repulsive electron-electron,
      rather than attractive electron-phonon, interactions.

PMID- 24336162
TI  - The impact of the TIM gene family on tumor immunity and immunosuppression.
AB  - Tumor immunoevasion is an advanced phase of cancer immunosurveillance in which
      tumor cells acquire the ability to circumvent host immune systems and exploit
      protumorigenic inflammation. T-cell immunoglobulin mucin (TIM) gene family
      members have emerged as critical checkpoint proteins that regulate multiple
      immune response phases and maintain immune homeostasis. Accumulating evidence
      demonstrates that tumor cells exploit TIM gene family members to evade
      immunosurveillance, whereas TIM gene family members facilitate the prevention of
      inflammation-related tumor progression. Thus, a comprehensive analysis to clarify
      the relative contributions of TIM gene family members in tumor progression may
      elucidate immunosurveillance systems in cancer patients. 

PMID- 24336164
TI  - The immunogenicity of cells derived from induced pluripotent stem cells.
AB  - With their ability to undergo unlimited self-renewal in culture and to
      differentiate into all cell types in the body, human embryonic stem cells (hESCs)
      hold great potential for the treatment of currently incurable diseases. Two hESC
      based cell therapies for spinal cord injury and macular degeneration have been
      advanced into human clinical trials. Despite this rapid progress, one key
      challenge of hESC-based cell therapy is the allogeneic immune rejection of hESC
      derived cells by recipients. This problem could be mitigated by a recent
      breakthrough in the technology of induced pluripotent stem cells (iPSCs) by
      nuclear reprogramming of patient-specific somatic cells with defined factors,
      which could become a renewable source of autologous cells for cell therapy.
      However, recent studies revealing the abnormal epigenetics, genomic stability and
      immunogenicity of iPSCs have raised safety concerns over iPSC-based therapy.
      Recent findings related to the immunogenicity of iPSC derivatives will be
      summarized in this review. 

PMID- 24336163
TI  - Induced pluripotent stem cell (iPSCs) and their application in immunotherapy.
AB  - The ever-improving technology to generate induced pluripotent stem cells (iPSCs)
      has increased their potential use as novel candidates for disease modeling, drug
      screening, regenerative medicine and cell therapy. Indeed, iPSCs offer extensive
      capacity for self-renewal without the ethical concerns faced by embryonic stem
      cells (ESCs). With respect to potential applications in the immune system, many
      studies provide evidence to support that there are exclusive advantages to using
      iPSCs over other systems. Both hematopoietic stem cells and several types of
      mature immune cells have successfully been reprogrammed to iPSCs and vice versa,
      paving a path toward our ability to effectively model patient-specific diseases
      and provide potentially alternative cell sources for transfusion medicine.
      Despite these potential advances, some limitations regarding the use of iPSCs in
      the clinic still remain, including the immunogenicity of iPSCs and their
      derivatives, which is currently under debate in the field. In this review, we
      mainly focus on discussing the recent progress being made in the latest
      differentiation methods and clinical implications of iPSCs with respect to the
      immune system. Additionally, current issues regarding the clinical application of
      iPSCs are addressed, especially the controversy surrounding immunogenicity, along
      with various other perspectives. 

PMID- 24336165
TI  - Microfluidic picoliter bioreactor for microbial single-cell analysis:
      fabrication, system setup, and operation.
AB  - In this protocol the fabrication, experimental setup and basic operation of the
      recently introduced microfluidic picoliter bioreactor (PLBR) is described in
      detail. The PLBR can be utilized for the analysis of single bacteria and
      microcolonies to investigate biotechnological and microbiological related
      questions concerning, e.g. cell growth, morphology, stress response, and
      metabolite or protein production on single-cell level. The device features
      continuous media flow enabling constant environmental conditions for perturbation
      studies, but in addition allows fast medium changes as well as oscillating
      conditions to mimic any desired environmental situation. To fabricate the single
      use devices, a silicon wafer containing sub micrometer sized SU-8 structures
      served as the replication mold for rapid polydimethylsiloxane casting. Chips were
      cut, assembled, connected, and set up onto a high resolution and fully automated
      microscope suited for time-lapse imaging, a powerful tool for spatio-temporal
      cell analysis. Here, the biotechnological platform organism Corynebacterium
      glutamicum was seeded into the PLBR and cell growth and intracellular
      fluorescence were followed over several hours unraveling time dependent
      population heterogeneity on single-cell level, not possible with conventional
      analysis methods such as flow cytometry. Besides insights into device
      fabrication, furthermore, the preparation of the preculture, loading, trapping of
      bacteria, and the PLBR cultivation of single cells and colonies is demonstrated.
      These devices will add a new dimension in microbiological research to analyze
      time dependent phenomena of single bacteria under tight environmental control.
      Due to the simple and relatively short fabrication process the technology can be
      easily adapted at any microfluidics lab and simply tailored towards specific
      needs. 

PMID- 24336166
TI  - Electrochemical monitoring systems of demembranated flagellate algal motility for
      ATP sensing.
AB  - The ATP-induced behavior of the unicellular flagellate alga Chlamydomonas
      reinhardtii was recorded as changes in the redox currents for a coexisting redox
      marker. The ATP concentration was estimated using the presented compact
      electrochemical system, which is based on monitoring of the motility of the
      flagellates. 

PMID- 24336167
TI  - Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to
      primary alterations in mitochondrial calcium signaling.
AB  - Mitochondrial Ca(2+) uptake has key roles in cell life and death. Physiological
      Ca(2+) signaling regulates aerobic metabolism, whereas pathological Ca(2+)
      overload triggers cell death. Mitochondrial Ca(2+) uptake is mediated by the
      Ca(2+) uniporter complex in the inner mitochondrial membrane, which comprises
      MCU, a Ca(2+)-selective ion channel, and its regulator, MICU1. Here we report
      mutations of MICU1 in individuals with a disease phenotype characterized by
      proximal myopathy, learning difficulties and a progressive extrapyramidal
      movement disorder. In fibroblasts from subjects with MICU1 mutations, agonist
      induced mitochondrial Ca(2+) uptake at low cytosolic Ca(2+) concentrations was
      increased, and cytosolic Ca(2+) signals were reduced. Although resting
      mitochondrial membrane potential was unchanged in MICU1-deficient cells, the
      mitochondrial network was severely fragmented. Whereas the pathophysiology of
      muscular dystrophy and the core myopathies involves abnormal mitochondrial Ca(2+)
      handling, the phenotype associated with MICU1 deficiency is caused by a primary
      defect in mitochondrial Ca(2+) signaling, demonstrating the crucial role of
      mitochondrial Ca(2+) uptake in humans. 

PMID- 24336168
TI  - Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in
      amyotrophic lateral sclerosis disease models.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal, late-onset neurodegenerative
      disease primarily affecting motor neurons. A unifying feature of many proteins
      associated with ALS, including TDP-43 and ataxin-2, is that they localize to
      stress granules. Unexpectedly, we found that genes that modulate stress granules
      are strong modifiers of TDP-43 toxicity in Saccharomyces cerevisiae and
      Drosophila melanogaster. eIF2alpha phosphorylation is upregulated by TDP-43
      toxicity in flies, and TDP-43 interacts with a central stress granule component,
      polyA-binding protein (PABP). In human ALS spinal cord neurons, PABP accumulates
      abnormally, suggesting that prolonged stress granule dysfunction may contribute
      to pathogenesis. We investigated the efficacy of a small molecule inhibitor of
      eIF2alpha phosphorylation in ALS models. Treatment with this inhibitor mitigated
      TDP-43 toxicity in flies and mammalian neurons. These findings indicate that the
      dysfunction induced by prolonged stress granule formation might contribute
      directly to ALS and that compounds that mitigate this process may represent a
      novel therapeutic approach. 

PMID- 24336169
TI  - Ionic leakage underlies a gain-of-function effect of dominant disease mutations
      affecting diverse P-type ATPases.
AB  - Type II P-type ATPases (PAIIs) constitute a family of conserved proteins that
      actively generate ionic gradients across membranes. Mutations in genes encoding
      PAIIs can cause heritable dominant diseases, with suggested etiology of
      haploinsufficiency. Using a Drosophila melanogaster genetic screen, we identified
      a dominant mutation altering the PAII member sarcoendoplasmic reticulum Ca(2+)
      ATPase (SERCA). This mutation conferred temperature-sensitive uncoordination in a
      gain-of-function manner. We established that this gain-of-function phenotype is
      linked to dominant disease-causing mutations affecting various human PAIIs. We
      further found that heterologous expression of mutant PAIIs elicited ion leakage
      that was exacerbated at elevated temperatures. Therefore, these dominant
      mutations result in ionic leakage and render PAIIs susceptible to deleterious
      effects from elevated temperatures. Accordingly, it was recently reported that
      missense mutations affecting the Na(+)/K(+) ATPase can elicit ionic leakage. We
      propose that ionic leakage is a pervasive gain-of-function mechanism that can
      underlie a variety of dominant PAII-related diseases. 

PMID- 24336171
TI  - Hierarchical SnO2 nanospheres: bio-inspired mineralization, vulcanization,
      oxidation techniques, and the application for NO sensors.
AB  - Controllable synthesis and surface engineering of nanomaterials are of strategic
      importance for tailoring their properties. Here, we demonstrate that the
      synthesis and surface adjustment of highly stable hierarchical of SnO2
      nanospheres can be realized by biomineralization, vulcanization and oxidation
      techniques. Furthermore, we reveal that the highly stable hierarchical SnO2
      nanospheres ensure a remarkable sensitivity towards NO gas with fast response and
      recovery due to their high crystallinity and special structure. Such technique
      acquiring highly stable hierarchical SnO2 nanospheres offers promising potential
      for future practical applications in monitoring the emission from waste
      incinerators and combustion process of fossil fuels. 

PMID- 24336170
TI  - Meta-analysis of gene-level tests for rare variant association.
AB  - The majority of reported complex disease associations for common genetic variants
      have been identified through meta-analysis, a powerful approach that enables the
      use of large sample sizes while protecting against common artifacts due to
      population structure and repeated small-sample analyses sharing individual-level
      data. As the focus of genetic association studies shifts to rare variants, genes
      and other functional units are becoming the focus of analysis. Here we propose
      and evaluate new approaches for performing meta-analysis of rare variant
      association tests, including burden tests, weighted burden tests, variable
      threshold tests and tests that allow variants with opposite effects to be grouped
      together. We show that our approach retains useful features from single-variant
      meta-analysis approaches and demonstrate its use in a study of blood lipid levels
      in ~18,500 individuals genotyped with exome arrays. 

PMID- 24336172
TI  - The impact of unprotected T cells in RNAi-based gene therapy for HIV-AIDS.
AB  - RNA interference (RNAi) is highly effective in inhibiting human immunodeficiency
      virus type 1 (HIV-1) replication by the expression of antiviral short hairpin RNA
      (shRNA) in stably transduced T-cell lines. For the development of a durable gene
      therapy that prevents viral escape, we proposed to combine multiple shRNAs
      against highly conserved regions of the HIV-1 RNA genome. The future in vivo
      application of such a gene therapy protocol will reach only a fraction of the T
      cells, such that HIV-1 replication will continue in the unmodified T cells,
      thereby possibly frustrating the therapy by generation of HIV-1 variants that
      escape from the inhibition imposed by the protected cells. We studied virus
      inhibition and evolution in pure cultures of shRNA-expressing cells versus mixed
      cell cultures of protected and unprotected T cells. The addition of the
      unprotected T cells indeed seems to accelerate HIV-1 evolution and escape from a
      single shRNA inhibitor. However, expression of three antiviral shRNAs from a
      single lentiviral vector prevents virus escape even in the presence of
      unprotected cells. These results support the idea to validate the therapeutic
      potential of this anti-HIV approach in appropriate in vivo models. 

PMID- 24336177
TI  - Microbiome: anelloviridae go viral.

PMID- 24336173
TI  - Sustained correction of motoneuron histopathology following intramuscular
      delivery of AAV in pompe mice.
AB  - Pompe disease is an autosomal recessive disorder caused by mutations in the acid
      alpha glucosidase (GAA) gene. Lingual dysfunction is prominent but does not
      respond to conventional enzyme replacement therapy (ERT). Using Pompe (Gaa(-/-))
      mice, we tested the hypothesis that intralingual delivery of viral vectors
      encoding GAA results in GAA expression and glycogen clearance in both tongue
      myofibers and hypoglossal (XII) motoneurons. An intralingual injection of an
      adeno-associated virus (AAV) vector encoding GAA (serotypes 1 or 9; 1 * 10(11)
      vector genomes, CMV promoter) was performed in 2-month-old Gaa(-/-) mice, and
      tissues were harvested 4 months later. Both serotypes robustly transduced tongue
      myofibers with histological confirmation of GAA expression (immunochemistry) and
      glycogen clearance (Period acid-Schiff stain). Both vectors also led to medullary
      transgene expression. GAA-positive motoneurons did not show the histopathologic
      features which are typical in Pompe disease and animal models. Intralingual
      injection with the AAV9 vector resulted in approximately threefold more GAA
      positive XII motoneurons (P < 0.02 versus AAV1); the AAV9 group also gained more
      body weight over the course of the study (P < 0.05 versus AAV1 and sham). We
      conclude that intralingual injection of AAV1 or AAV9 drives persistent GAA
      expression in tongue myofibers and motoneurons, but AAV9 may more effectively
      target motoneurons. 

PMID- 24336178
TI  - Microbiome: TLR5 puts the brakes on.

PMID- 24336180
TI  - Environmental microbiology: disentangling syntrophy.

PMID- 24336181
TI  - Your gut microbiota are what you eat.

PMID- 24336182
TI  - Exploring bacterial cell biology with single-molecule tracking and super
      resolution imaging.
AB  - The ability to detect single molecules in live bacterial cells enables us to
      probe biological events one molecule at a time and thereby gain knowledge of the
      activities of intracellular molecules that remain obscure in conventional
      ensemble-averaged measurements. Single-molecule fluorescence tracking and super
      resolution imaging are thus providing a new window into bacterial cells and
      facilitating the elucidation of cellular processes at an unprecedented level of
      sensitivity, specificity and spatial resolution. In this Review, we consider what
      these technologies have taught us about the bacterial cytoskeleton, nucleoid
      organization and the dynamic processes of transcription and translation, and we
      also highlight the methodological improvements that are needed to address a
      number of experimental challenges in the field. 

PMID- 24336183
TI  - Ribosome-targeting antibiotics and mechanisms of bacterial resistance.
AB  - The ribosome is one of the main antibiotic targets in the bacterial cell. Crystal
      structures of naturally produced antibiotics and their semi-synthetic derivatives
      bound to ribosomal particles have provided unparalleled insight into their
      mechanisms of action, and they are also facilitating the design of more effective
      antibiotics for targeting multidrug-resistant bacteria. In this Review, I discuss
      the recent structural insights into the mechanism of action of ribosome-targeting
      antibiotics and the molecular mechanisms of bacterial resistance, in addition to
      the approaches that are being pursued for the production of improved drugs that
      inhibit bacterial protein synthesis. 

PMID- 24336187
TI  - Hierarchical Li4Ti5O12/TiO2 composite tubes with regular structural imperfection
      for lithium ion storage.
AB  - Hierarchical Li4Ti5O12/TiO2 tubes composed of ultrathin nanoflakes have been
      successfully fabricated via the calcination of the hydrothermal product of a
      porous amorphous TiO2 precursor and lithium hydroxide monohydrate. The
      hierarchical tubes are characterized by powder X-ray diffraction, nitrogen
      adsorption/desorption, scanning electron microscopy and transmission electron
      microscopy techniques. These nanoflakes exhibit a quite complex submicroscopic
      structure with regular structural imperfection, including a huge number of grain
      boundaries and dislocations. The lithium ion storage property of these tubes is
      evaluated by galvanostatic discharge/charge experiment. The product shows initial
      discharge capacities of 420, 225, and 160 mAh g(-1) at 0.01, 0.1, and 1.0 A g(
      1), respectively. After 100 cycles, the discharge capacity is 139 mAh g(-1) at
      1.0 A g(-1) with a capacity retention of 87%, demonstrating good high-rate
      performance and good cycleability. The high electrochemical performance is
      attributed to unique structure and morphology of the tubes. The regular
      structural imperfection existed in the nanoflakes also benefit to lithium ion
      storage property of these tubes. The hierarchical Li4Ti5O12/TiO2 tubes are a
      promising anode material for lithium-ion batteries with high power and energy
      densities. 

PMID- 24336185
TI  - Bacterial programmed cell death: making sense of a paradox.
AB  - Although the concept of programmed cell death (PCD) in bacteria has been met with
      scepticism, a growing body of evidence suggests that it can no longer be ignored.
      Several recent studies indicate that the phenotypic manifestations of apoptosis,
      which are processes that are associated with ordered cellular disassembly in
      eukaryotes, are conserved in bacteria. In this Opinion article, I propose a model
      for the coordinated control of potential bacterial PCD effectors and argue that
      the processes involved are functionally analogous to eukaryotic PCD systems.

PMID- 24336184
TI  - Adhesion, invasion and evasion: the many functions of the surface proteins of
      Staphylococcus aureus.
AB  - Staphylococcus aureus is an important opportunistic pathogen and persistently
      colonizes about 20% of the human population. Its surface is 'decorated' with
      proteins that are covalently anchored to the cell wall peptidoglycan. Structural
      and functional analysis has identified four distinct classes of surface proteins,
      of which microbial surface component recognizing adhesive matrix molecules
      (MSCRAMMs) are the largest class. These surface proteins have numerous functions,
      including adhesion to and invasion of host cells and tissues, evasion of immune
      responses and biofilm formation. Thus, cell wall-anchored proteins are essential
      virulence factors for the survival of S. aureus in the commensal state and during
      invasive infections, and targeting them with vaccines could combat S. aureus
      infections. 

PMID- 24336188
TI  - Increases in terrestrially derived carbon stimulate organic carbon processing and
      CO2 emissions in boreal aquatic ecosystems.
AB  - The concentrations of terrestrially derived dissolved organic carbon have been
      increasing throughout northern aquatic ecosystems in recent decades, but whether
      these shifts have an impact on aquatic carbon emissions at the continental scale
      depends on the potential for this terrestrial carbon to be converted into carbon
      dioxide. Here, via the analysis of hundreds of boreal lakes, rivers and wetlands
      in Canada, we show that, contrary to conventional assumptions, the proportion of
      biologically degradable dissolved organic carbon remains constant and the
      photochemical degradability increases with terrestrial influence. Thus,
      degradation potential increases with increasing amounts of terrestrial carbon.
      Our results provide empirical evidence of a strong causal link between dissolved
      organic carbon concentrations and aquatic fluxes of carbon dioxide, mediated by
      the degradation of land-derived organic carbon in aquatic ecosystems. Future
      shifts in the patterns of terrestrial dissolved organic carbon in inland waters
      thus have the potential to significantly increase aquatic carbon emissions across
      northern landscapes. 

PMID- 24336189
TI  - Using an automated 3D-tracking system to record individual and shoals of adult
      zebrafish.
AB  - Like many aquatic animals, zebrafish (Danio rerio) moves in a 3D space. It is
      thus preferable to use a 3D recording system to study its behavior. The presented
      automatic video tracking system accomplishes this by using a mirror system and a
      calibration procedure that corrects for the considerable error introduced by the
      transition of light from water to air. With this system it is possible to record
      both single and groups of adult zebrafish. Before use, the system has to be
      calibrated. The system consists of three modules: Recording, Path Reconstruction,
      and Data Processing. The step-by-step protocols for calibration and using the
      three modules are presented. Depending on the experimental setup, the system can
      be used for testing neophobia, white aversion, social cohesion, motor
      impairments, novel object exploration etc. It is especially promising as a first
      step tool to study the effects of drugs or mutations on basic behavioral
      patterns. The system provides information about vertical and horizontal
      distribution of the zebrafish, about the xyz-components of kinematic parameters
      (such as locomotion, velocity, acceleration, and turning angle) and it provides
      the data necessary to calculate parameters for social cohesions when testing
      shoals. 

PMID- 24336190
TI  - Reference dosimetry for light-ion beams based on graphite calorimetry.
AB  - Developments in hadron therapy require efforts to improve the accuracy of the
      dose delivered to a target volume. Here, the determination of the absorbed dose
      under reference conditions was analysed. Based on the International Atomic Energy
      Agency TRS-398 code of practice, for hadron beams, the combined standard
      uncertainty on absorbed dose to water under reference conditions, derived from
      ionisation chambers, is too large. This uncertainty is dominated by the beam
      quality correction factors, [Formula: see text], mainly due to the mean energy to
      produce one ion pair in air, wair. A method to reduce this uncertainty is to
      carry out primary dosimetry, using calorimetry. A [Formula: see text]-value can
      be derived from a direct comparison between calorimetry and ionometry. Here, this
      comparison is performed using a graphite calorimeter in an 80-MeV A(-1) carbon
      ion beam. Assuming recommended TRS-398 values of water-to-graphite stopping power
      ratio and the perturbation factor for an ionisation chamber, preliminary results
      indicate a wair-value of 35.5 +/- 0.9 J C(-1). 

PMID- 24336191
TI  - The restrictions to the use of codeine and dilemmas about safe alternatives.

PMID- 24336193
TI  - The relative mRNA expression of p53 isoforms in breast cancer is associated with
      clinical features and outcome.
AB  - Mutation of p53 is a common feature of cancer. Breast cancer is the most common
      malignancy that develops in women; however, somatic mutation of p53 is rare,
      suggesting that p53 becomes inactivated by other mechanisms. p53 is expressed as
      smaller isoforms, some of which inhibit wild-type p53. There are no studies that
      have examined the relative expression of all isoforms in this disease. We have
      analysed the relative messenger RNA expression of the p53 isoforms, Delta40,
      Delta133, beta and gamma in a panel of 6 breast cancer cell lines, 148 breast
      cancers specimens and 31 matched normal adjacent tissues by semi-quantitative
      real-time reverse transcription-PCR and analysed their relationship to clinical
      features and outcome. We have identified several important clinical associations,
      particularly with Delta40p53, which was expressed at levels that were ~50-fold
      higher than the least expressed isoform p53gamma. Delta40p53 was significantly
      upregulated in tumour tissue when compared with the normal breast and was
      significantly associated with an aggressive breast cancer subtype-triple
      negative. Additionally, p53beta expression was significantly negatively
      associated with tumour size and positively associated with disease-free survival,
      where high levels of p53beta were protective, particularly in patients with a
      mutation in p53, suggesting p53beta may counteract the damage inflicted by mutant
      p53. In conclusion, the relative expression of p53 isoforms is related to
      clinical features of breast cancer and outcome. These results have implications
      for the stratification of breast cancer based on p53 function and may provide an
      alternate explanation for deregulated p53 signalling in breast cancer.

PMID- 24336192
TI  - Age at cancer onset in germline TP53 mutation carriers: association with
      polymorphisms in predicted G-quadruplex structures.
AB  - Germline TP53 mutations predispose to multiple cancers defining Li-Fraumeni/Li
      Fraumeni-like syndrome (LFS/LFL), a disease with large individual disparities in
      cancer profiles and age of onset. G-quadruplexes (G4s) are secondary structural
      motifs occurring in guanine tracks, with regulatory effects on DNA and RNA. We
      analyzed 85 polymorphisms within or near five predicted G4s in TP53 in search of
      modifiers of penetrance of LFS/LFL in Brazilian cancer families with (n = 35) or
      without (n = 110) TP53 mutations. Statistical analyses stratified on family
      structure showed that cancer tended to occur ~15 years later in mutation carriers
      who also carried the variant alleles of two polymorphisms within predicted G4
      forming regions, rs17878362 (TP53 PIN3, 16 bp duplication in intron 3; P = 0.082)
      and rs17880560 (6 bp duplication in 3' flanking region; P = 0.067). Haplotype
      analysis showed that this inverse association was driven by the polymorphic
      status of the remaining wild-type (WT) haplotype in mutation carriers: in
      carriers with a WT haplotype containing at least one variant allele of rs17878362
      or rs17880560, cancer occurred ~15 years later than in carriers with other WT
      haplotypes (P = 0.019). No effect on age of cancer onset was observed in subjects
      without a TP53 mutation. The G4 in intron 3 has been shown to regulate
      alternative p53 messenger RNA splicing, whereas the biological roles of predicted
      G4s in the 3' flanking region remain to be elucidated. In conclusion, this study
      demonstrates that G4 polymorphisms in haplotypes of the WT TP53 allele have an
      impact on LFS/LFL penetrance in germline TP53 mutation carriers. 

PMID- 24336194
TI  - Differential effects of 2- and 3-series E-prostaglandins on in vitro expansion of
      Lgr5+ colonic stem cells.
AB  - Arachidonic acid (20:4(Delta5,8,11,14), AA)-derived prostaglandin E2 (PGE2)
      promotes colon cancer development. In contrast, chemoprotective n-3
      polyunsaturated fatty acids supplant AA, thereby decreasing PGE2 biosynthesis in
      colonocytes, with eicosapentaenoic acid (20:5(Delta5,8,11,14,17), EPA) in
      particular being metabolized to a novel 3-series E-prostaglandin (PGE3), a
      putative anti-tumorigenic-cyclooxygenase metabolite. Because transformation of
      adult stem cells is an extremely important route toward initiating intestinal
      cancer, we utilized the leucine-rich-repeat-containing G-protein-coupled receptor
      5 (Lgr5)-enhanced green fluorescent protein-internal ribosome entry site (IRES)
      creER(T2) knock-in mouse model to isolate and culture colonic organoids, in order
      to document ex vivo responses to exogenous PGE2 and PGE3. Colonic crypts were
      isolated from transgenic mice and cultured in a Matrigel-based three-dimensional
      platform. Organoids were treated with exogenous PGE2, PGE3 or dimethyl sulfoxide
      (vehicle control) for 5 days and the number of viable organoids was recorded
      daily. Subsequently, samples were processed for immunohistochemistry, flow
      cytometry and real-time PCR analyses. PGE2 promoted optimal organoid growth and
      induced significantly higher levels of cell proliferation (P < 0.05) compared
      with PGE3 and control. In contrast, the Lgr5-green fluorescent protein-positive
      stem cell number was uniquely elevated by >2-fold in PGE2-treated cultures
      compared with PGE3 and control. This coincided with the upregulation of stem-cell
      related Sox9, Axin2 and Cd44 messenger RNAs. Our results demonstrate that
      relative to AA-derived PGE2, a known promoter of colon tumorigenesis, EPA-derived
      PGE3 has diminished ability to support colonic stem cell expansion in mouse
      colonic organoids.

PMID- 24336198
TI  - Structural basis of lentiviral subversion of a cellular protein degradation
      pathway.
AB  - Lentiviruses contain accessory genes that have evolved to counteract the effects
      of host cellular defence proteins that inhibit productive infection. One such
      restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1
      infection of myeloid-lineage cells as well as resting CD4(+) T cells by reducing
      the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at
      which the viral reverse transcriptase cannot function. In other lentiviruses,
      including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1
      restriction is overcome by the action of viral accessory protein x (Vpx) or the
      related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal
      degradation. The molecular mechanism by which these viral proteins are able to
      usurp the host cell's ubiquitination machinery to destroy the cell's protection
      against these viruses has not been defined. Here we present the crystal structure
      of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and
      the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical
      bundle stabilized by a zinc finger motif, and wraps tightly around the disc
      shaped DCAF1 molecule to present a new molecular surface. This adapted surface is
      then able to recruit SAMHD1 via its C terminus, making it a competent substrate
      for the E3 ligase to mark for proteasomal degradation. The structure reported
      here provides a molecular description of how a lentiviral accessory protein is
      able to subvert the cell's normal protein degradation pathway to inactivate the
      cellular viral defence system. 

PMID- 24336199
TI  - Amazon River carbon dioxide outgassing fuelled by wetlands.
AB  - River systems connect the terrestrial biosphere, the atmosphere and the ocean in
      the global carbon cycle. A recent estimate suggests that up to 3 petagrams of
      carbon per year could be emitted as carbon dioxide (CO2) from global inland
      waters, offsetting the carbon uptake by terrestrial ecosystems. It is generally
      assumed that inland waters emit carbon that has been previously fixed upstream by
      land plant photosynthesis, then transferred to soils, and subsequently
      transported downstream in run-off. But at the scale of entire drainage basins,
      the lateral carbon fluxes carried by small rivers upstream do not account for all
      of the CO2 emitted from inundated areas downstream. Three-quarters of the world's
      flooded land consists of temporary wetlands, but the contribution of these
      productive ecosystems to the inland water carbon budget has been largely
      overlooked. Here we show that wetlands pump large amounts of atmospheric CO2 into
      river waters in the floodplains of the central Amazon. Flooded forests and
      floating vegetation export large amounts of carbon to river waters and the
      dissolved CO2 can be transported dozens to hundreds of kilometres downstream
      before being emitted. We estimate that Amazonian wetlands export half of their
      gross primary production to river waters as dissolved CO2 and organic carbon,
      compared with only a few per cent of gross primary production exported in upland
      (not flooded) ecosystems. Moreover, we suggest that wetland carbon export is
      potentially large enough to account for at least the 0.21 petagrams of carbon
      emitted per year as CO2 from the central Amazon River and its floodplains. Global
      carbon budgets should explicitly address temporary or vegetated flooded areas,
      because these ecosystems combine high aerial primary production with large, fast
      carbon export, potentially supporting a substantial fraction of CO2 evasion from
      inland waters. 

PMID- 24336200
TI  - DWARF 53 acts as a repressor of strigolactone signalling in rice.
AB  - Strigolactones (SLs) are a group of newly identified plant hormones that control
      plant shoot branching. SL signalling requires the hormone-dependent interaction
      of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box
      component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we
      report the characterization of a dominant SL-insensitive rice (Oryza sativa)
      mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the
      SCF(D3) ubiquitination complex and functions as a repressor of SL signalling.
      Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the
      proteasome in a manner that requires D14 and the SCF(D3) ubiquitin ligase,
      whereas the dominant form of D53 is resistant to SL-mediated degradation.
      Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS
      RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL
      dependent degradation of the D53 repressor mediated by the D14-D3 complex. 

PMID- 24336201
TI  - Cytokinin signalling inhibitory fields provide robustness to phyllotaxis.
AB  - How biological systems generate reproducible patterns with high precision is a
      central question in science. The shoot apical meristem (SAM), a specialized
      tissue producing plant aerial organs, is a developmental system of choice to
      address this question. Organs are periodically initiated at the SAM at specific
      spatial positions and this spatiotemporal pattern defines phyllotaxis.
      Accumulation of the plant hormone auxin triggers organ initiation, whereas auxin
      depletion around organs generates inhibitory fields that are thought to be
      sufficient to maintain these patterns and their dynamics. Here we show that
      another type of hormone-based inhibitory fields, generated directly downstream of
      auxin by intercellular movement of the cytokinin signalling inhibitor ARABIDOPSIS
      HISTIDINE PHOSPHOTRANSFER PROTEIN 6 (AHP6), is involved in regulating
      phyllotactic patterns. We demonstrate that AHP6-based fields establish patterns
      of cytokinin signalling in the meristem that contribute to the robustness of
      phyllotaxis by imposing a temporal sequence on organ initiation. Our findings
      indicate that not one but two distinct hormone-based fields may be required for
      achieving temporal precision during formation of reiterative structures at the
      SAM, thus indicating an original mechanism for providing robustness to a dynamic
      developmental system. 

PMID- 24336203
TI  - Retraction: GlcNAcylation of a histone methyltransferase in retinoic-acid-induced
      granulopoiesis.

PMID- 24336202
TI  - C/EBPalpha poises B cells for rapid reprogramming into induced pluripotent stem
      cells.
AB  - CCAAT/enhancer binding protein-alpha (C/EBPalpha) induces transdifferentiation of
      B cells into macrophages at high efficiencies and enhances reprogramming into
      induced pluripotent stem (iPS) cells when co-expressed with the transcription
      factors Oct4 (Pou5f1), Sox2, Klf4 and Myc (hereafter called OSKM). However, how
      C/EBPalpha accomplishes these effects is unclear. Here we find that in mouse
      primary B cells transient C/EBPalpha expression followed by OSKM activation
      induces a 100-fold increase in iPS cell reprogramming efficiency, involving 95%
      of the population. During this conversion, pluripotency and epithelial
      mesenchymal transition genes become markedly upregulated, and 60% of the cells
      express Oct4 within 2 days. C/EBPalpha acts as a 'path-breaker' as it transiently
      makes the chromatin of pluripotency genes more accessible to DNase I. C/EBPalpha
      also induces the expression of the dioxygenase Tet2 and promotes its
      translocation to the nucleus where it binds to regulatory regions of pluripotency
      genes that become demethylated after OSKM induction. In line with these findings,
      overexpression of Tet2 enhances OSKM-induced B-cell reprogramming. Because the
      enzyme is also required for efficient C/EBPalpha-induced immune cell conversion,
      our data indicate that Tet2 provides a mechanistic link between iPS cell
      reprogramming and B-cell transdifferentiation. The rapid iPS reprogramming
      approach described here should help to fully elucidate the process and has
      potential clinical applications. 

PMID- 24336204
TI  - Plant biology: Witchcraft and destruction.

PMID- 24336205
TI  - Icosahedral bacteriophage PhiX174 forms a tail for DNA transport during
      infection.
AB  - Prokaryotic viruses have evolved various mechanisms to transport their genomes
      across bacterial cell walls. Many bacteriophages use a tail to perform this
      function, whereas tail-less phages rely on host organelles. However, the tail
      less, icosahedral, single-stranded DNA PhiX174-like coliphages do not fall into
      these well-defined infection processes. For these phages, DNA delivery requires a
      DNA pilot protein. Here we show that the PhiX174 pilot protein H oligomerizes to
      form a tube whose function is most probably to deliver the DNA genome across the
      host's periplasmic space to the cytoplasm. The 2.4 A resolution crystal structure
      of the in vitro assembled H protein's central domain consists of a 170 A-long
      alpha-helical barrel. The tube is constructed of ten alpha-helices with their
      amino termini arrayed in a right-handed super-helical coiled-coil and their
      carboxy termini arrayed in a left-handed super-helical coiled-coil. Genetic and
      biochemical studies demonstrate that the tube is essential for infectivity but
      does not affect in vivo virus assembly. Cryo-electron tomograms show that tubes
      span the periplasmic space and are present while the genome is being delivered
      into the host cell's cytoplasm. Both ends of the H protein contain transmembrane
      domains, which anchor the assembled tubes into the inner and outer cell
      membranes. The central channel of the H-protein tube is lined with amide and
      guanidinium side chains. This may be a general property of viral DNA conduits and
      is likely to be critical for efficient genome translocation into the host. 

PMID- 24336207
TI  - Nanoparticle solutions as adhesives for gels and biological tissues.
AB  - Adhesives are made of polymers because, unlike other materials, polymers ensure
      good contact between surfaces by covering asperities, and retard the fracture of
      adhesive joints by dissipating energy under stress. But using polymers to 'glue'
      together polymer gels is difficult, requiring chemical reactions, heating, pH
      changes, ultraviolet irradiation or an electric field. Here we show that strong,
      rapid adhesion between two hydrogels can be achieved at room temperature by
      spreading a droplet of a nanoparticle solution on one gel's surface and then
      bringing the other gel into contact with it. The method relies on the
      nanoparticles' ability to adsorb onto polymer gels and to act as connectors
      between polymer chains, and on the ability of polymer chains to reorganize and
      dissipate energy under stress when adsorbed onto nanoparticles. We demonstrate
      this approach by pressing together pieces of hydrogels, for approximately 30
      seconds, that have the same or different chemical properties or rigidities, using
      various solutions of silica nanoparticles, to achieve a strong bond. Furthermore,
      we show that carbon nanotubes and cellulose nanocrystals that do not bond
      hydrogels together become adhesive when their surface chemistry is modified. To
      illustrate the promise of the method for biological tissues, we also glued
      together two cut pieces of calf's liver using a solution of silica nanoparticles.
      As a rapid, simple and efficient way to assemble gels or tissues, this method is
      desirable for many emerging technological and medical applications such as
      microfluidics, actuation, tissue engineering and surgery. 

PMID- 24336209
TI  - Unidirectional pulmonary airflow patterns in the savannah monitor lizard.
AB  - The unidirectional airflow patterns in the lungs of birds have long been
      considered a unique and specialized trait associated with the oxygen demands of
      flying, their endothermic metabolism and unusual pulmonary architecture. However,
      the discovery of similar flow patterns in the lungs of crocodilians indicates
      that this character is probably ancestral for all archosaurs--the group that
      includes extant birds and crocodilians as well as their extinct relatives, such
      as pterosaurs and dinosaurs. Unidirectional flow in birds results from
      aerodynamic valves, rather than from sphincters or other physical mechanisms, and
      similar aerodynamic valves seem to be present in crocodilians. The anatomical and
      developmental similarities in the primary and secondary bronchi of birds and
      crocodilians suggest that these structures and airflow patterns may be
      homologous. The origin of this pattern is at least as old as the split between
      crocodilians and birds, which occurred in the Triassic period. Alternatively,
      this pattern of flow may be even older; this hypothesis can be tested by
      investigating patterns of airflow in members of the outgroup to birds and
      crocodilians, the Lepidosauromorpha (tuatara, lizards and snakes). Here we
      demonstrate region-specific unidirectional airflow in the lungs of the savannah
      monitor lizard (Varanus exanthematicus). The presence of unidirectional flow in
      the lungs of V. exanthematicus thus gives rise to two possible evolutionary
      scenarios: either unidirectional airflow evolved independently in archosaurs and
      monitor lizards, or these flow patterns are homologous in archosaurs and V.
      exanthematicus, having evolved only once in ancestral diapsids (the clade
      encompassing snakes, lizards, crocodilians and birds). If unidirectional airflow
      is plesiomorphic for Diapsida, this respiratory character can be reconstructed
      for extinct diapsids, and evolved in a small ectothermic tetrapod during the
      Palaeozoic era at least a hundred million years before the origin of birds.

PMID- 24336210
TI  - A new metabolic cell-wall labelling method reveals peptidoglycan in Chlamydia
      trachomatis.
AB  - Peptidoglycan (PG), an essential structure in the cell walls of the vast majority
      of bacteria, is critical for division and maintaining cell shape and hydrostatic
      pressure. Bacteria comprising the Chlamydiales were thought to be one of the few
      exceptions. Chlamydia harbour genes for PG biosynthesis and exhibit
      susceptibility to 'anti-PG' antibiotics, yet attempts to detect PG in any
      chlamydial species have proven unsuccessful (the 'chlamydial anomaly'). We used a
      novel approach to metabolically label chlamydial PG using d-amino acid dipeptide
      probes and click chemistry. Replicating Chlamydia trachomatis were labelled with
      these probes throughout their biphasic developmental life cycle, and the results
      of differential probe incorporation experiments conducted in the presence of
      ampicillin are consistent with the presence of chlamydial PG-modifying enzymes.
      These findings culminate 50 years of speculation and debate concerning the
      chlamydial anomaly and are the strongest evidence so far that chlamydial species
      possess functional PG. 

PMID- 24336208
TI  - Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's
      disease.
AB  - Genome-wide association studies (GWAS) have identified several risk variants for
      late-onset Alzheimer's disease (LOAD). These common variants have replicable but
      small effects on LOAD risk and generally do not have obvious functional effects.
      Low-frequency coding variants, not detected by GWAS, are predicted to include
      functional variants with larger effects on risk. To identify low-frequency coding
      variants with large effects on LOAD risk, we carried out whole-exome sequencing
      (WES) in 14 large LOAD families and follow-up analyses of the candidate variants
      in several large LOAD case-control data sets. A rare variant in PLD3
      (phospholipase D3; Val232Met) segregated with disease status in two independent
      families and doubled risk for Alzheimer's disease in seven independent case
      control series with a total of more than 11,000 cases and controls of European
      descent. Gene-based burden analyses in 4,387 cases and controls of European
      descent and 302 African American cases and controls, with complete sequence data
      for PLD3, reveal that several variants in this gene increase risk for Alzheimer's
      disease in both populations. PLD3 is highly expressed in brain regions that are
      vulnerable to Alzheimer's disease pathology, including hippocampus and cortex,
      and is expressed at significantly lower levels in neurons from Alzheimer's
      disease brains compared to control brains. Overexpression of PLD3 leads to a
      significant decrease in intracellular amyloid-beta precursor protein (APP) and
      extracellular Abeta42 and Abeta40 (the 42- and 40-residue isoforms of the amyloid
      beta peptide), and knockdown of PLD3 leads to a significant increase in
      extracellular Abeta42 and Abeta40. Together, our genetic and functional data
      indicate that carriers of PLD3 coding variants have a twofold increased risk for
      LOAD and that PLD3 influences APP processing. This study provides an example of
      how densely affected families may help to identify rare variants with large
      effects on risk for disease or other complex traits. 

PMID- 24336212
TI  - Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma
      brucei.
AB  - The protozoan parasites Trypanosoma brucei spp. cause important human and
      livestock diseases in sub-Saharan Africa. In mammalian blood, two developmental
      forms of the parasite exist: proliferative 'slender' forms and arrested 'stumpy'
      forms that are responsible for transmission to tsetse flies. The slender to
      stumpy differentiation is a density-dependent response that resembles quorum
      sensing in microbial systems and is crucial for the parasite life cycle, ensuring
      both infection chronicity and disease transmission. This response is triggered by
      an elusive 'stumpy induction factor' (SIF) whose intracellular signalling pathway
      is also uncharacterized. Laboratory-adapted (monomorphic) trypanosome strains
      respond inefficiently to SIF but can generate forms with stumpy characteristics
      when exposed to cell-permeable cAMP and AMP analogues. Exploiting this, we have
      used a genome-wide RNA interference library screen to identify the signalling
      components driving stumpy formation. In separate screens, monomorphic parasites
      were exposed to 8-(4-chlorophenylthio)-cAMP (pCPT-cAMP) or 8-pCPT-2'-O-methyl-5'
      AMP to select cells that were unresponsive to these signals and hence remained
      proliferative. Genome-wide Ion Torrent based RNAi target sequencing identified
      cohorts of genes implicated in each step of the signalling pathway, from purine
      metabolism, through signal transducers (kinases, phosphatases) to gene expression
      regulators. Genes at each step were independently validated in cells naturally
      capable of stumpy formation, confirming their role in density sensing in vivo.
      The putative RNA-binding protein, RBP7, was required for normal quorum sensing
      and promoted cell-cycle arrest and transmission competence when overexpressed.
      This study reveals that quorum sensing signalling in trypanosomes shares
      similarities to fundamental quiescence pathways in eukaryotic cells, its
      components providing targets for quorum-sensing interference-based therapeutics. 

PMID- 24336213
TI  - Mycobacteria manipulate macrophage recruitment through coordinated use of
      membrane lipids.
AB  - The evolutionary survival of Mycobacterium tuberculosis, the cause of human
      tuberculosis, depends on its ability to invade the host, replicate, and transmit
      infection. At its initial peripheral infection site in the distal lung airways,
      M. tuberculosis infects macrophages, which transport it to deeper tissues. How
      mycobacteria survive in these broadly microbicidal cells is an important
      question. Here we show in mice and zebrafish that M. tuberculosis, and its close
      pathogenic relative Mycobacterium marinum, preferentially recruit and infect
      permissive macrophages while evading microbicidal ones. This immune evasion is
      accomplished by using cell-surface-associated phthiocerol dimycoceroserate (PDIM)
      lipids to mask underlying pathogen-associated molecular patterns (PAMPs). In the
      absence of PDIM, these PAMPs signal a Toll-like receptor (TLR)-dependent
      recruitment of macrophages that produce microbicidal reactive nitrogen species.
      Concordantly, the related phenolic glycolipids (PGLs) promote the recruitment of
      permissive macrophages through a host chemokine receptor 2 (CCR2)-mediated
      pathway. Thus, we have identified coordinated roles for PDIM, known to be
      essential for mycobacterial virulence, and PGL, which (along with CCR2) is known
      to be associated with human tuberculosis. Our findings also suggest an
      explanation for the longstanding observation that M. tuberculosis initiates
      infection in the relatively sterile environment of the lower respiratory tract,
      rather than in the upper respiratory tract, where resident microflora and inhaled
      environmental microbes may continually recruit microbicidal macrophages through
      TLR-dependent signalling. 

PMID- 24336214
TI  - Genome-wide probing of RNA structure reveals active unfolding of mRNA structures
      in vivo.
AB  - RNA has a dual role as an informational molecule and a direct effector of
      biological tasks. The latter function is enabled by RNA's ability to adopt
      complex secondary and tertiary folds and thus has motivated extensive
      computational and experimental efforts for determining RNA structures. Existing
      approaches for evaluating RNA structure have been largely limited to in vitro
      systems, yet the thermodynamic forces which drive RNA folding in vitro may not be
      sufficient to predict stable RNA structures in vivo. Indeed, the presence of RNA
      binding proteins and ATP-dependent helicases can influence which structures are
      present inside cells. Here we present an approach for globally monitoring RNA
      structure in native conditions in vivo with single-nucleotide precision. This
      method is based on in vivo modification with dimethyl sulphate (DMS), which
      reacts with unpaired adenine and cytosine residues, followed by deep sequencing
      to monitor modifications. Our data from yeast and mammalian cells are in
      excellent agreement with known messenger RNA structures and with the high
      resolution crystal structure of the Saccharomyces cerevisiae ribosome. Comparison
      between in vivo and in vitro data reveals that in rapidly dividing cells there
      are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable
      RNA structures are often denatured in cells, highlighting the importance of
      cellular processes in regulating RNA structure. Indeed, analysis of mRNA
      structure under ATP-depleted conditions in yeast shows that energy-dependent
      processes strongly contribute to the predominantly unfolded state of mRNAs inside
      cells. Our studies broadly enable the functional analysis of physiological RNA
      structures and reveal that, in contrast to the Anfinsen view of protein folding
      whereby the structure formed is the most thermodynamically favourable,
      thermodynamics have an incomplete role in determining mRNA structure in vivo. 

PMID- 24336215
TI  - D14-SCF(D3)-dependent degradation of D53 regulates strigolactone signalling.
AB  - Strigolactones (SLs), a newly discovered class of carotenoid-derived
      phytohormones, are essential for developmental processes that shape plant
      architecture and interactions with parasitic weeds and symbiotic arbuscular
      mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic
      pathway, the perception and signalling mechanisms of SL remain poorly understood.
      Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that
      SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant,
      which produces an exaggerated number of tillers compared to wild-type plants, is
      caused by a gain-of-function mutation and is insensitive to exogenous SL
      treatment. The D53 gene product shares predicted features with the class I Clp
      ATPase proteins and can form a complex with the alpha/beta hydrolase protein
      DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified
      signalling components potentially responsible for SL perception. We demonstrate
      that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the
      proteasome and abrogate its activity in promoting axillary bud outgrowth. Our
      combined genetic and biochemical data reveal that D53 acts as a repressor of the
      SL signalling pathway, whose hormone-induced degradation represents a key
      molecular link between SL perception and responses. 

PMID- 24336216
TI  - Increasing subtropical North Pacific Ocean nitrogen fixation since the Little Ice
      Age.
AB  - The North Pacific subtropical gyre (NPSG) plays a major part in the export of
      carbon and other nutrients to the deep ocean. Primary production in the NPSG has
      increased in recent decades despite a reduction in nutrient supply to surface
      waters. It is thought that this apparent paradox can be explained by a shift in
      plankton community structure from mostly eukaryotes to mostly nitrogen-fixing
      prokaryotes. It remains uncertain, however, whether the plankton community domain
      shift can be linked to cyclical climate variability or a long-term global warming
      trend. Here we analyse records of bulk and amino-acid-specific (15)N/(14)N
      isotopic ratios (delta(15)N) preserved in the skeletons of long-lived deep-sea
      proteinaceous corals collected from the Hawaiian archipelago; these isotopic
      records serve as a proxy for the source of nitrogen-supported export production
      through time. We find that the recent increase in nitrogen fixation is the
      continuation of a much larger, centennial-scale trend. After a millennium of
      relatively minor fluctuation, delta(15)N decreases between 1850 and the present.
      The total shift in delta(15)N of -2 per mil over this period is comparable to the
      total change in global mean sedimentary delta(15)N across the Pleistocene
      Holocene transition, but it is happening an order of magnitude faster. We use a
      steady-state model and find that the isotopic mass balance between nitrate and
      nitrogen fixation implies a 17 to 27 per cent increase in nitrogen fixation over
      this time period. A comparison with independent records suggests that the
      increase in nitrogen fixation might be linked to Northern Hemisphere climate
      change since the end of the Little Ice Age. 

PMID- 24336218
TI  - Face-to-face transfer of wafer-scale graphene films.
AB  - Graphene has attracted worldwide interest since its experimental discovery, but
      the preparation of large-area, continuous graphene film on SiO2/Si wafers, free
      from growth-related morphological defects or transfer-induced cracks and folds,
      remains a formidable challenge. Growth of graphene by chemical vapour deposition
      on Cu foils has emerged as a powerful technique owing to its compatibility with
      industrial-scale roll-to-roll technology. However, the polycrystalline nature and
      microscopic roughness of Cu foils means that such roll-to-roll transferred films
      are not devoid of cracks and folds. High-fidelity transfer or direct growth of
      high-quality graphene films on arbitrary substrates is needed to enable wide
      ranging applications in photonics or electronics, which include devices such as
      optoelectronic modulators, transistors, on-chip biosensors and tunnelling
      barriers. The direct growth of graphene film on an insulating substrate, such as
      a SiO2/Si wafer, would be useful for this purpose, but current research efforts
      remain grounded at the proof-of-concept stage, where only discontinuous,
      nanometre-sized islands can be obtained. Here we develop a face-to-face transfer
      method for wafer-scale graphene films that is so far the only known way to
      accomplish both the growth and transfer steps on one wafer. This spontaneous
      transfer method relies on nascent gas bubbles and capillary bridges between the
      graphene film and the underlying substrate during etching of the metal catalyst,
      which is analogous to the method used by tree frogs to remain attached to
      submerged leaves. In contrast to the previous wet or dry transfer results, the
      face-to-face transfer does not have to be done by hand and is compatible with any
      size and shape of substrate; this approach also enjoys the benefit of a much
      reduced density of transfer defects compared with the conventional transfer
      method. Most importantly, the direct growth and spontaneous attachment of
      graphene on the underlying substrate is amenable to batch processing in a
      semiconductor production line, and thus will speed up the technological
      application of graphene. 

PMID- 24336217
TI  - Diet rapidly and reproducibly alters the human gut microbiome.
AB  - Long-term dietary intake influences the structure and activity of the trillions
      of microorganisms residing in the human gut, but it remains unclear how rapidly
      and reproducibly the human gut microbiome responds to short-term macronutrient
      change. Here we show that the short-term consumption of diets composed entirely
      of animal or plant products alters microbial community structure and overwhelms
      inter-individual differences in microbial gene expression. The animal-based diet
      increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and
      Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant
      polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii).
      Microbial activity mirrored differences between herbivorous and carnivorous
      mammals, reflecting trade-offs between carbohydrate and protein fermentation.
      Foodborne microbes from both diets transiently colonized the gut, including
      bacteria, fungi and even viruses. Finally, increases in the abundance and
      activity of Bilophila wadsworthia on the animal-based diet support a link between
      dietary fat, bile acids and the outgrowth of microorganisms capable of triggering
      inflammatory bowel disease. In concert, these results demonstrate that the gut
      microbiome can rapidly respond to altered diet, potentially facilitating the
      diversity of human dietary lifestyles. 

PMID- 24336219
TI  - A comparative study of carbon-platinum hybrid nanostructure architecture for
      amperometric biosensing.
AB  - Carbon and noble metal nanomaterials exhibit unique properties that have been
      explored over the last few decades for developing electrochemical sensors and
      biosensors. Hybridization of nanometals to carbon nanomaterials such as graphene
      or carbon nanotubes produces a synergistic effect on the electrocatalytic
      activity when compared to either material alone. However, to date there are no
      comparative studies that directly investigate the effects of nanocarbon
      concentration and nanocomposite arrangement on electron transport. This
      comparative study investigated the efficacy of various platinum-carbon hybrid
      nanostructures for amperometric biosensing. Electroactive surface area,
      sensitivity towards hydrogen peroxide, response time, limit of detection, and
      surface roughness were measured for various hybrid nanomaterial arrangements.
      Both design factors (nanocarbon concentration and network arrangement) influenced
      the performance of the reduced graphene oxide-based platforms; whereas only
      nanomaterial arrangement affected the performance of the carbon nanotube
      composites. The highest sensitivity towards hydrogen peroxide for reduced
      graphene oxide nanocomposites (45 +/- 3.2 MUA mM(-1)) was measured for a graphene
      concentration of 2 mg mL(-1) in a "sandwich" structure; nanoplatinum layers
      enveloping the reduced graphene oxide. Likewise, the best carbon nanotube
      performance toward H2O2 (49 +/- 1.4 MUA mM(-1)) was measured for a sandwich-type
      structure with nanoplatinum. The enhanced electrocatalytic activity of this
      "sandwich" structure was due to a combined effect of electrical junctions formed
      amongst nanocarbon, and nanocomposite soldering to the electrode surface. The top
      down carbon-platinum hybrid nanocomposites in this paper represent a simple, low
      cost, approach for formation of high fidelity amperometric sensors with
      remarkable performance characteristics that are similar to bottom-up fabrication
      approaches. 

PMID- 24336220
TI  - Visualization of distinct substrate-recruitment pathways in the yeast exosome by
      EM.
AB  - The eukaryotic exosome is a multisubunit complex typically composed of a
      catalytically inactive core and the Rrp44 protein, which contains 3'-to-5' exo-
      and endo-RNase activities. RNA substrates have been shown to be recruited through
      the core to reach Rrp44's exo-RNase (EXO) site. Using single-particle EM and
      biochemical analysis, we provide visual evidence that two distinct substrate
      recruitment pathways exist. In the through-core route, channeling of the single
      stranded substrates from the core to Rrp44 induces a characteristic
      conformational change in Rrp44. In the alternative direct-access route, this
      conformational change does not take place, and the RNA substrate is visualized to
      avoid the core and enter Rrp44's EXO site directly. Our results provide
      mechanistic explanations for several RNA processing scenarios by the eukaryotic
      exosome and indicate substrate-specific modes of degradation by this complex. 

PMID- 24336221
TI  - Dynamics of yeast histone H2A and H2B phosphorylation in response to a double
      strand break.
AB  - In budding yeast, a single double-strand break (DSB) triggers extensive Tel1
      (ATM)- and Mec1 (ATR)-dependent phosphorylation of histone H2A around the DSB, to
      form gamma-H2AX. We describe Mec1- and Tel1-dependent phosphorylation of histone
      H2B at T129. gamma-H2B formation is impaired by gamma-H2AX and its binding
      partner Rad9. High-density microarray analyses show similar gamma-H2AX and gamma
      H2B distributions, but gamma-H2B is absent near telomeres. Both gamma-H2AX and
      gamma-H2B are strongly diminished over highly transcribed regions. When
      transcription of GAL7, GAL10 and GAL1 genes is turned off, gamma-H2AX is restored
      within 5 min, in a Mec1-dependent manner; after reinduction of these genes, gamma
      H2AX is rapidly lost. Moreover, when a DSB is induced near CEN2, gamma-H2AX
      spreads to all other pericentromeric regions, again depending on Mec1. Our data
      provide new insights in the function and establishment of phosphorylation events
      occurring on chromatin after DSB induction. 

PMID- 24336222
TI  - Establishment of methylation patterns in ES cells.
AB  - After erasure in the early animal embryo, a new bimodal DNA methylation pattern
      is regenerated at implantation. We have identified a demethylation pathway in
      mouse embryonic cells that uses hydroxymethylation (Tet1), deamination (Aid),
      glycosylation (Mbd4) and excision repair (Gadd45a) genes. Surprisingly, this
      demethylation system is not necessary for generating the overall bimodal
      methylation pattern but does appear to be involved in resetting methylation
      patterns during somatic-cell reprogramming. 

PMID- 24336223
TI  - Staufen1 senses overall transcript secondary structure to regulate translation.
AB  - Human Staufen1 (Stau1) is a double-stranded RNA (dsRNA)-binding protein
      implicated in multiple post-transcriptional gene-regulatory processes. Here we
      combined RNA immunoprecipitation in tandem (RIPiT) with RNase footprinting,
      formaldehyde cross-linking, sonication-mediated RNA fragmentation and deep
      sequencing to map Staufen1-binding sites transcriptome wide. We find that Stau1
      binds complex secondary structures containing multiple short helices, many of
      which are formed by inverted Alu elements in annotated 3' untranslated regions
      (UTRs) or in 'strongly distal' 3' UTRs. Stau1 also interacts with actively
      translating ribosomes and with mRNA coding sequences (CDSs) and 3' UTRs in
      proportion to their GC content and propensity to form internal secondary
      structure. On mRNAs with high CDS GC content, higher Stau1 levels lead to greater
      ribosome densities, thus suggesting a general role for Stau1 in modulating
      translation elongation through structured CDS regions. Our results also indicate
      that Stau1 regulates translation of transcription-regulatory proteins. 

PMID- 24336224
TI  - Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis.
AB  - DNA methylation occurs in CG and non-CG sequence contexts. Non-CG methylation is
      abundant in plants and is mediated by CHROMOMETHYLASE (CMT) and DOMAINS
      REARRANGED METHYLTRANSFERASE (DRM) proteins; however, its roles remain poorly
      understood. Here we characterize the roles of non-CG methylation in Arabidopsis
      thaliana. We show that a poorly characterized methyltransferase, CMT2, is a
      functional methyltransferase in vitro and in vivo. CMT2 preferentially binds
      histone H3 Lys9 (H3K9) dimethylation and methylates non-CG cytosines that are
      regulated by H3K9 methylation. We revealed the contributions and redundancies
      between each non-CG methyltransferase in DNA methylation patterning and in
      regulating transcription. We also demonstrate extensive dependencies of small-RNA
      accumulation and H3K9 methylation patterning on non-CG methylation, suggesting
      self-reinforcing mechanisms between these epigenetic factors. The results suggest
      that non-CG methylation patterns are critical in shaping the landscapes of
      histone modification and small noncoding RNA. 

PMID- 24336225
TI  - Three-dimensional strutted graphene grown by substrate-free sugar blowing for
      high-power-density supercapacitors.
AB  - Three-dimensional graphene architectures in the macroworld can in principle
      maintain all the extraordinary nanoscale properties of individual graphene
      flakes. However, current 3D graphene products suffer from poor electrical
      conductivity, low surface area and insufficient mechanical strength/elasticity;
      the interconnected self-supported reproducible 3D graphenes remain unavailable.
      Here we report a sugar-blowing approach based on a polymeric predecessor to
      synthesize a 3D graphene bubble network. The bubble network consists of mono- or
      few-layered graphitic membranes that are tightly glued, rigidly fixed and
      spatially scaffolded by micrometre-scale graphitic struts. Such a topological
      configuration provides intimate structural interconnectivities, freeway for
      electron/phonon transports, huge accessible surface area, as well as robust
      mechanical properties. The graphene network thus overcomes the drawbacks of
      presently available 3D graphene products and opens up a wide horizon for diverse
      practical usages, for example, high-power high-energy electrochemical capacitors,
      as highlighted in this work. 

PMID- 24336227
TI  - Pairwise Sequence Alignment for Very Long Sequences on GPUs.
AB  - We develop novel single-GPU parallelizations of the Smith-Waterman algorithm for
      pairwise sequence alignment. Our algorithms, which are suitable for the alignment
      of a single pair of very long sequences, can be used to determine the alignment
      score as well as the actual alignment. Experimental results demonstrate an order
      of magnitude reduction in run time relative to competing GPU algorithms.

PMID- 24336228
TI  - Phase transformation evolution in NiTi shape memory alloy under cyclic
      nanoindentation loadings at dissimilar rates.
AB  - Hysteresis energy decreased significantly as nanocrystalline NiTi shape memory
      alloy was under triangular cyclic nanoindentation loadings at high rate. Jagged
      curves evidenced discrete stress relaxations. With a large recovery state of
      maximum deformation in each cycle, this behavior concluded in several nucleation
      sites of phase transformation in stressed bulk. Additionally, the higher initial
      propagation velocity of interface and thermal activation volume, and higher
      levels of phase transition stress in subsequent cycles explained the monotonic
      decreasing trend of dissipated energy. In contrast, the dissipated energy showed
      an opposite increasing trend during triangular cyclic loadings at a low rate and
      60 sec holding time after each unloading stage. Due to the isothermal loading
      rate and the holding time, a major part of the released latent heat was
      transferred during the cyclic loading resulting in an unchanged phase transition
      stress. This fact with the reorientation phenomenon explained the monotonic
      increasing trend of hysteresis energy. 

PMID- 24336226
TI  - Molecular signatures of antibody responses derived from a systems biology study
      of five human vaccines.
AB  - Many vaccines induce protective immunity via antibodies. Systems biology
      approaches have been used to determine signatures that can be used to predict
      vaccine-induced immunity in humans, but whether there is a 'universal signature'
      that can be used to predict antibody responses to any vaccine is unknown. Here we
      did systems analyses of immune responses to the polysaccharide and conjugate
      vaccines against meningococcus in healthy adults, in the broader context of
      published studies of vaccines against yellow fever virus and influenza virus. To
      achieve this, we did a large-scale network integration of publicly available
      human blood transcriptomes and systems-scale databases in specific biological
      contexts and deduced a set of transcription modules in blood. Those modules
      revealed distinct transcriptional signatures of antibody responses to different
      classes of vaccines, which provided key insights into primary viral, protein
      recall and anti-polysaccharide responses. Our results elucidate the early
      transcriptional programs that orchestrate vaccine immunity in humans and
      demonstrate the power of integrative network modeling. 

PMID- 24336229
TI  - Hereditary diffuse leukoencephalopathy with axonal spheroids: more than just a
      rare disease.

PMID- 24336231
TI  - Locomotion of microspheres for super-resolution imaging.
AB  - Super-resolution virtual imaging by micron sized transparent beads (microspheres)
      was recently demonstrated by Wang et al. Practical applications in microscopy
      require control over the positioning of the microspheres. Here we present a
      method of positioning and controllable movement of a microsphere by using a fine
      glass micropipette. This allows sub-diffraction imaging at arbitrary points in
      three dimensions, as well as the ability to track moving objects. The results are
      relevant to a broad scope of applications, including sample inspection,
      microfabrication, and bio-imaging. 

PMID- 24336230
TI  - Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients
      with HDLS.
AB  - OBJECTIVE: To clarify the genetic, clinicopathologic, and neuroimaging
      characteristics of patients with hereditary diffuse leukoencephalopathy with
      spheroids (HDLS) with the colony stimulating factor 1 receptor (CSF-1R) mutation.
      METHODS: We performed molecular genetic analysis of CSF-1R in patients with HDLS.
      Detailed clinical and neuroimaging findings were retrospectively investigated.
      Five patients were examined neuropathologically. RESULTS: We found 6 different
      CSF-1R mutations in 7 index patients from unrelated Japanese families. The CSF-1R
      mutations included 3 novel mutations and 1 known missense mutation at
      evolutionarily conserved amino acids, and 1 novel splice-site mutation. We
      identified a novel frameshift mutation. Reverse transcription PCR analysis
      revealed that the frameshift mutation causes nonsense-mediated mRNA decay by
      generating a premature stop codon, suggesting that haploinsufficiency of CSF-1R
      is sufficient to cause HDLS. Western blot analysis revealed that the expression
      level of CSF-1R in the brain from the patients was lower than from control
      subjects. The characteristic MRI findings were the involvement of the white
      matter and thinning of the corpus callosum with signal alteration, and sequential
      analysis revealed that the white matter lesions and cerebral atrophy relentlessly
      progressed with disease duration. Spotty calcifications in the white matter were
      frequently observed by CT. Neuropathologic analysis revealed that microglia in
      the brains of the patients demonstrated distinct morphology and distribution.
      CONCLUSIONS: These findings suggest that patients with HDLS, irrespective of
      mutation type in CSF-1R, show characteristic clinical and neuroimaging features,
      and that perturbation of CSF-1R signaling by haploinsufficiency may play a role
      in microglial dysfunction leading to the pathogenesis of HDLS.

PMID- 24336232
TI  - Fifteen-year disability trends among older persons in the Beijing municipality of
      China.
AB  - OBJECTIVE: The aim of this study was to examine disability trends among men and
      women aged 70+ in Beijing, China; determine whether trends are impacted upon by
      changes in population composition; and investigate whether trends are experienced
      similarly across socio-demographic subgroups. METHOD: Fifteen-year panel data
      were used to model probability of reporting activities of daily living (ADLs)
      disability adjusting for age, sex, marital status, residence, and education.
      Predicted probabilities and average annual percent change in probabilities are
      reported. RESULTS: The results showed increasing disability trends experienced by
      men, and stable or decreasing trends by women. Trends would be less favorable had
      education of older population not increased over time. Trends are much worse when
      bathing is excluded as an ADLs item. This is because trends in bathing were
      favorable whereas trends in other activities were not. DISCUSSION: On balance,
      results are not overly encouraging for reductions in population-level disability
      given population aging and increasing life expectancy in China. But, future
      increasing education could mitigate some increases in disability rates.

PMID- 24336233
TI  - The relationship between older Americans act in-home services and low-care
      residents in nursing homes.
AB  - OBJECTIVE: The aim of the study was to investigate the relationship between
      supportive services provided under Title III-B of the Older Americans Act (OAA)
      and the prevalence of low-care residents in nursing homes (NHs). METHOD: State
      Program Reports (state-level expenditure and utilization data for each OAA
      service) and NH facility-level data were analyzed using a two-way fixed effects
      model. RESULTS: Results suggest that every additional 1% of the population age
      65+ that receives personal care services is associated with a 0.8% decrease in
      the proportion of low-care residents in NHs. DISCUSSION: Despite efforts to
      rebalance long-term care, there are still many NH residents who have the
      functional capacity to live in a less restrictive environment. This is among the
      first studies to suggest that states that have invested in their in-home
      supportive services, particularly personal care services provided through the
      OAA, have proportionally fewer of these people.

PMID- 24336234
TI  - Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine
      sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.
AB  - Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a
      variety of functions in the nervous, gastrointestinal and cardiovascular systems.
      Despite such importance, 5-HT signaling pathways are not entirely clear. We
      demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K(+)
      (Kv) channels determine the resting membrane potential of arterial smooth muscle
      cells and that the Kv channels are inhibited by 5-HT, which depolarizes the
      membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting
      Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents
      in rat mesenteric arteries using patch-clamp and isometric tension measurements.
      Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial
      rings, whereas inhibiting Ca(2+)-activated K(+), inward rectifier K(+) and ATP
      sensitive K(+) channels had little effect on arterial contraction, indicating a
      central role of Kv channels in the regulation of resting arterial tone. 5-HT
      induced arterial contraction decreased significantly in the presence of high KCl
      or the voltage-gated Ca(2+) channel (VGCC) inhibitor nifedipine, indicating that
      membrane depolarization and the consequent activation of VGCCs mediate the 5-HT
      induced vasoconstriction. The effects of 5-HT on Kv currents and arterial
      contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin
      and spiperone. Consistently, alpha-methyl 5-HT, a 5-HT2 receptor agonist,
      mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase
      inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine,
      prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our
      data suggest that 4-AP-sensitive Kv channels are the primary regulator of the
      resting tone in rat mesenteric arteries. 5-HT constricts the arteries by
      inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway. 

PMID- 24336236
TI  - Breastfeeding duration and cognitive, language and motor development at 18 months
      of age: Rhea mother-child cohort in Crete, Greece.
AB  - BACKGROUND: Breast feeding duration has been associated with improved cognitive
      development in children. However, few population-based prospective studies have
      evaluated dose-response relationships of breastfeeding duration with language and
      motor development at early ages, and results are discrepant. METHODS: The study
      uses data from the prospective mother-child cohort ('Rhea' study) in Crete,
      Greece. 540 mother-child pairs were included in the present analysis. Information
      about parental and child characteristics and breastfeeding practices was obtained
      by interview-administered questionnaires. Trained psychologists assessed
      cognitive, language and motor development by using the Bayley Scales of Infant
      Toddler Development (3rd edition) at the age of 18 months. RESULTS: Duration of
      breast feeding was linearly positively associated with all the Bayley scales,
      except of gross motor. The association persisted after adjustment for potential
      confounders with an increase of 0.28 points in the scale of cognitive development
      (beta=0.28; 95% CI 0.01 to 0.55), 0.29 points in the scale of receptive
      communication (beta=0.29; 95% CI 0.04 to 0.54), 0.30 points in the scale of
      expressive communication (beta=0.30; 95% CI 0.04 to 0.57) and 0.29 points in the
      scale of fine motor development (beta=0.29; 95% CI 0.02 to 0.56) per accumulated
      month of breast feeding. Children who were breast fed longer than 6 months had a
      4.44-point increase in the scale of fine motor development (beta=4.44; 95% CI
      0.06 to 8.82) compared with those never breast fed. CONCLUSIONS: Longer duration
      of breast feeding was associated with increased scores in cognitive, language and
      motor development at 18 months of age, independently from a wide range of
      parental and infant characteristics. Additional longitudinal studies and trials
      are needed to confirm these results.

PMID- 24336235
TI  - Heaviness, health and happiness: a cross-sectional study of 163066 UK Biobank
      participants.
AB  - BACKGROUND: Obesity is known to increase the risk of many diseases and reduce
      overall quality of life. This study examines the relationship with self-reported
      health (SRH) and happiness. METHODS: We conducted a cross-sectional study of the
      163 066 UK Biobank participants who completed the happiness rating. The
      association between adiposity and SRH and happiness was examined using logistic
      regression. SRH was defined as good (excellent, good), or poor (fair, poor). Self
      reported happiness was defined as happy (extremely, very, moderately) or unhappy
      (moderately, very, extremely). RESULTS: Poor health was reported by 44 457
      (27.3%) participants. The adjusted ORs for poor health were 3.86, 2.92, 2.60 and
      6.41 for the highest, compared with lowest, deciles of Body Mass Index, waist
      circumference, waist to hip ratio and body fat percent, respectively. The
      associations were stronger in men (p<0.001). Overall, 7511 (4.6%) participants
      felt unhappy, and only class III obese participants were more likely to feel
      unhappy (adjusted OR 1.33, 95% CI 1.15 to 1.53, p<0.001) but the associations
      differed by sex (p<0.001). Among women, there was a significant association
      between unhappiness and all levels of obesity. By contrast, only class III obese
      men had significantly increased risk and overweight and class I obese men were
      less likely to be unhappy. CONCLUSIONS: Obesity impacts adversely on happiness as
      well as health, but the association with unhappiness disappeared after adjustment
      for self-reported health, indicating this may be mediated by health. Compared
      with obese men, obese women are less likely to report poor health, but more
      likely to feel unhappy.

PMID- 24336237
TI  - Adverse effects of public health interventions: a conceptual framework.
AB  - Public health interventions may have a range of adverse effects. However, there
      is limited guidance as to how evaluations should address the possibility of
      adverse effects. This discussion paper briefly presents a framework for thinking
      about the potential harms of public health interventions, focusing on the
      following categories: direct harms; psychological harms; equity harms; group and
      social harms; and opportunity harms. We conclude that the possibility of adverse
      effects needs to be taken into account by those implementing and evaluating
      interventions, and requires a broad perspective on the potential impacts of
      public health strategies. 

PMID- 24336238
TI  - The influence of ethnicity on breastfeeding rates in Ireland: a cross-sectional
      study.
AB  - BACKGROUND: Historically, breastfeeding rates in Ireland have been low compared
      with international averages. It has been suggested that maternal ethnicity and
      citizenship may influence breastfeeding rates, with ethnic minorities thought
      more likely to breast feed. AIM: The aim of this study is to investigate the
      association among maternal citizenship, ethnicity, birthplace and breast feeding.
      It is hypothesised that Irish mothers (identified through Irish citizenship, self
      identified Irish ethnicity or Irish birthplace) are less likely to breast feed
      than non-Irish mothers. METHODS: The study population of Growing Up in Ireland:
      the National Longitudinal Study of Children was used for this study. Analysis was
      restricted to 11 092 biological mother and infant pairs with a complete
      breastfeeding history. Logistic regression analysis was used to estimate ORs and
      95% CIs for breast feeding relative to maternal citizenship and ethnicity,
      controlling for the confounding effects of other maternal variables. RESULTS:
      Results indicated that 55.9% (6202 of 11 092) of mothers had initiated breast
      feeding, with only 7.9% (874 of 11 092) of mothers currently breast feeding their
      infant (at 9 months of age). Irish citizens (4693 of 9368, 50.0%) were
      significantly less likely to have initiated breast feeding compared with non
      Irish citizens (1503 of 1695, 88.7%). Irish born mothers (4179 of 8627, 48.8%)
      were also significantly less likely to have initiated breast feeding than mothers
      born elsewhere (2023 of 2462, 82.2%). CONCLUSIONS: Maternal citizenship and
      ethnicity appear to be the strongest influencing factors on breastfeeding
      initiation and duration. However, this raises a possibility that the increase in
      breastfeeding rates seen recently may be the result of increased immigration into
      Ireland, rather than the success of policy and research efforts.

PMID- 24336239
TI  - Immediate mobilization after coronary angiography or percutaneous coronary
      intervention following hemostasis with the AngioSeal vascular closure device (the
      MOBS study).
AB  - BACKGROUND: In patients undergoing coronary angiography or percutaneous coronary
      intervention (PCI), the standard post procedure regime includes immobilization
      and bed rest despite the use of vascular closure devices. AIM: In the
      Mobilization after Coronary Angiography or Percutaneous Coronary Intervention
      (MOBS) study we compared bleeding complications after cardiac catheterization
      with femoral artery access after mobilization immediately off the angiographic
      table or standard care with1 hour (MOBS I after a diagnostic angiogram) or 2
      hours of bed rest before mobilization (MOBS II after PCI). METHODS: Bleeding
      complications were defined as major (requiring surgery of the femoral artery,
      transfusion or increased hospital stay) and minor (hematoma <5 * 5 cm(2), oozing
      from the puncture site or minor bleeding that could be compressed manually).
      RESULTS: In the MOBS I cohort (100 patients were mobilized immediately and 100
      patients followed standard care) no major bleeding complications were seen. In
      the immediate mobilization group 2.0% experienced minor bleeding compared to 4.0%
      in the standard care group (p=0.41). In the MOBS II cohort after PCI (158
      patients were mobilized immediately and 161 patients followed standard care),
      major bleeding complication rates did not differ significantly between the two
      groups: immediate mobilization group 26.6% vs. standard care group 28.0%, p=0.78.
      The majority of bleeding complications were due to oozing: immediate mobilization
      group 22.8% vs. standard care group 20.5%, p=0.62. CONCLUSIONS: Immediate
      mobilization after a coronary angiogram or PCI with the femoral access site
      closed by the closure device AngioSeal was not associated with increased bleeding
      risk compared to standard care with bed rest.

PMID- 24336240
TI  - Interaction modes and approaches to glycopeptide and glycoprotein enrichment.
AB  - Protein glycosylation has received increased attention for its critical role in
      cell biology and diseases. Developing new methodologies to discern phenotype
      dependent glycosylation will not only elucidate the mechanistic aspects of cell
      signaling cascades but also accelerate biomarker discovery for disease diagnosis
      or prognosis. In the analytical pipeline, enrichment at either the protein or
      peptide level is the most critical prerequisite for analyzing heterogeneous
      glycan composition, linkage, site occupancy and carrier proteins. Because the
      critical factor for choosing a suitable enrichment method is primarily a
      particular technique's selectivity and affinity towards target
      glycoproteins/glycopeptides, it is important to fully understand the working
      principles for the different approaches. For mechanistic insight into the
      enrichment protocol, we focused on the fundamental chemical and physical
      processes for the commonly used approaches based on: (a) glycan/peptide
      physicochemical properties (hydrophilic interactions, chelation/coordination
      chemistry) and (b) glycan-specific recognition (lectin-based affinity, covalent
      bond formation by hydrazide/boronic acid). Various interaction modes, such as
      hydrogen bonding, van der Waals interaction, multivalency, and metal- or water
      mediated stabilization, are discussed in detail. In addition, we will review the
      design of and modifications to such methods, hyphenated approaches, and
      glycoproteomic applications. Finally, we will outline challenges to existing
      strategies and offer novel proposals for glycoproteome enrichment. 

PMID- 24336241
TI  - Optical conductivity of nodal metals.
AB  - Fermi liquid theory is remarkably successful in describing the transport and
      optical properties of metals; at frequencies higher than the scattering rate, the
      optical conductivity adopts the well-known power law behavior sigma1(omega) ?
      omega(-2). We have observed an unusual non-Fermi liquid response sigma1(omega) ?
      omega(-1+/-0.2) in the ground states of several cuprate and iron-based materials
      which undergo electronic or magnetic phase transitions resulting in dramatically
      reduced or nodal Fermi surfaces. The identification of an inverse (or fractional)
      power-law behavior in the residual optical conductivity now permits the removal
      of this contribution, revealing the direct transitions across the gap and
      allowing the nature of the electron-boson coupling to be probed. The non-Fermi
      liquid behavior in these systems may be the result of a common Fermi surface
      topology of Dirac cone-like features in the electronic dispersion. 

PMID- 24336243
TI  - Extended follow-up of WHI finds 'complex' pattern of risk and benefit.

PMID- 24336244
TI  - The effect of hormones on the lower urinary tract.
AB  - The female genital and lower urinary tracts share a common embryological origin,
      arising from the urogenital sinus and both are sensitive to the effects of the
      female sex steroid hormones throughout life. Estrogen is known to have an
      important role in the function of the lower urinary tract and estrogen and
      progesterone receptors have been demonstrated in the vagina, urethra, bladder and
      pelvic floor musculature. In addition estrogen deficiency occurring following the
      menopause is known to cause atrophic change and may be associated with lower
      urinary tract symptoms such as frequency, urgency, nocturia, urgency incontinence
      and recurrent infection. These may also co-exist with symptoms of urogenital
      atrophy such as dyspareunia, itching, vaginal burning and dryness.
      Epidemiological studies have implicated estrogen deficiency in the aetiology of
      lower urinary tract symptoms with 70% of women relating the onset of urinary
      incontinence to their final menstrual period. Whilst for many years systemic and
      vaginal estrogen therapy was felt to be beneficial in the treatment of lower
      urinary and genital tract symptoms this evidence has recently been challenged by
      large epidemiological studies investigating the use of systemic hormone
      replacement therapy as primary and secondary prevention of cardiovascular disease
      and osteoporosis. The aim of this paper is to examine the effect of the sex
      hormones, estrogen and progesterone, on the lower urinary tract and to review the
      current evidence regarding the role of systemic and vaginal estrogens in the
      management of lower urinary tract symptoms and urogenital atrophy. 

PMID- 24336245
TI  - Stand by your man: the importance of the female in male sexual problems.

PMID- 24336246
TI  - Should HRT be duration limited?
AB  - Hormone Replacement Therapy (HRT) has received consistently bad press, despite re
      analysis of previous data new studies and supporting Consensus Statements from
      leading national and international societies. Many women have been convinced by
      women's journals and the media not to even consider HRT as an option and, General
      Practitioners, still limit duration to 5 years or, will, arbitrarily, discontinue
      prescriptions in the early 50s. This article seeks to make sense of our current
      position. Previous and new evidence on the safety of HRT is reviewed. New data on
      the long-term consequences of non-treatment of women with Premature Ovarian
      Insufficiency (POI) is presented and the dichotomy of the older female workforce
      is explored. From this, a logical plan of management emerges. 

PMID- 24336247
TI  - The clathrin adaptor Numb regulates intestinal cholesterol absorption through
      dynamic interaction with NPC1L1.
AB  - Hypercholesterolemia, typically due to excessive cholesterol uptake, is a major
      risk factor for cardiovascular disease, which is responsible for ~50% of all
      deaths in developed societies. Although it has been shown that intestinal
      cholesterol absorption is mediated by vesicular endocytosis of the Niemann-Pick
      C1-like 1 (NPC1L1) protein, the mechanism of sterol-stimulated NPC1L1
      internalization is still mysterious. Here, we identified an endocytic peptide
      signal, YVNXXF (where X stands for any amino acid), in the cytoplasmic C-terminal
      tail of NPC1L1. Cholesterol binding on the N-terminal domain of NPC1L1 released
      the YVNXXF-containing region of NPC1L1 from association with the plasma membrane
      and enabled Numb binding. We also found that Numb, a clathrin adaptor,
      specifically recognized this motif and recruited clathrin for internalization.
      Disrupting the NPC1L1-Numb interaction decreased cholesterol uptake. Ablation of
      Numb in mouse intestine significantly reduced dietary cholesterol absorption and
      plasma cholesterol level. Together, these data show that Numb is a pivotal
      protein for intestinal cholesterol absorption and may provide a therapeutic
      target for hypercholesterolemia. 

PMID- 24336248
TI  - Sterilization of granulomas is common in active and latent tuberculosis despite
      within-host variability in bacterial killing.
AB  - Over 30% of the world's population is infected with Mycobacterium tuberculosis
      (Mtb), yet only ~5-10% will develop clinical disease. Despite considerable
      effort, researchers understand little about what distinguishes individuals whose
      infection progresses to active tuberculosis (TB) from those whose infection
      remains latent for decades. The variable course of disease is recapitulated in
      cynomolgus macaques infected with Mtb. Active disease occurs in ~45% of infected
      macaques and is defined by clinical, microbiologic and immunologic signs, whereas
      the remaining infected animals are clinically asymptomatic. Here, we use
      individually marked Mtb isolates and quantitative measures of culturable and
      cumulative bacterial burden to show that most lung lesions are probably founded
      by a single bacterium and reach similar maximum burdens. Despite this
      observation, the fate of individual lesions varies substantially within the same
      host. Notably, in active disease, the host sterilizes some lesions even while
      others progress. Our data suggest that lesional heterogeneity arises, in part,
      through differential killing of bacteria after the onset of adaptive immunity.
      Thus, individual lesions follow diverse and overlapping trajectories, suggesting
      that critical responses occur at a lesional level to ultimately determine the
      clinical outcome of infection. Defining the local factors that dictate outcome
      will be useful in developing effective interventions to prevent active TB. 

PMID- 24336250
TI  - Preserve the European Research Council's legacy.

PMID- 24336262
TI  - Fungus threatens top banana.

PMID- 24336249
TI  - Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome
      facilitate obesity-associated airway hyperreactivity.
AB  - Obesity is associated with the development of asthma, which is often difficult to
      control. To understand the immunological pathways that lead to obesity-associated
      asthma, we fed mice a high-fat diet for 12 weeks, which resulted in obesity and
      the development of airway hyperreactivity (AHR), a cardinal feature of asthma.
      This AHR was independent of adaptive immunity, as it occurred in obese Rag1(-/-)
      mice, which lack B and T cells, and was dependent on interleukin-17A (IL-17A) and
      the NLRP3 inflammasome, as it did not develop in obese Il17a(-/-) or Nlrp3(-/-)
      mice. AHR was also associated with the expansion of CCR6(+) type 3 innate
      lymphoid cells (ILCs) producing IL-17A (ILC3 cells) in the lung, which could by
      themselves mediate AHR when adoptively transferred into Rag2(-/-); Il2rg(-/-)
      mice treated with recombinant IL-1beta. Macrophage-derived IL-1beta production
      was induced by HFD and expanded the number of lung ILC3 cells. Blockade of IL
      1beta with an IL-1 receptor antagonist abolished obesity-induced AHR and reduced
      the number of ILC3 cells. As we found ILC3-like cells in the bronchoalveolar
      lavage fluid of individuals with asthma, we suggest that obesity-associated
      asthma is facilitated by inflammation mediated by NLRP3, IL-1beta and ILC3 cells.

PMID- 24336263
TI  - Florida forecasts sinkhole burden.

PMID- 24336264
TI  - Diabetes drugs ride a bumpy road.

PMID- 24336265
TI  - Food fuelled with fungi.

PMID- 24336266
TI  - India faces uphill battle on biodiversity.

PMID- 24336268
TI  - Life possible in the early Universe.

PMID- 24336269
TI  - Radioisotopes: The medical testing crisis.

PMID- 24336270
TI  - Earth science: Under the volcano.

PMID- 24336274
TI  - Cross-border science: Universities aid EU research mobility.

PMID- 24336275
TI  - Training: African database for education schemes.

PMID- 24336276
TI  - Pathogens: Appeal for funds to fight banana blight.

PMID- 24336277
TI  - Marine infrastructure: NSF fleet vital for ocean science.

PMID- 24336278
TI  - Extrasolar planets: Inner edge of the habitable zone.

PMID- 24336279
TI  - Developmental biology: Mechanics in the embryo.

PMID- 24336280
TI  - Astrophysics: Tracking our neighbours' past.

PMID- 24336281
TI  - Neuroscience: The highs and lows of memory.

PMID- 24336282
TI  - Soft-matter physics: Ferromagnetic ferrofluids.

PMID- 24336284
TI  - Ferromagnetism in suspensions of magnetic platelets in liquid crystal.
AB  - More than four decades ago, Brochard and de Gennes proposed that colloidal
      suspensions of ferromagnetic particles in nematic (directionally ordered) liquid
      crystals could form macroscopic ferromagnetic phases at room temperature. The
      experimental realization of these predicted phases has hitherto proved elusive,
      with such systems showing enhanced paramagnetism but no spontaneous magnetization
      in the absence of an external magnetic field. Here we show that nanometre-sized
      ferromagnetic platelets suspended in a nematic liquid crystal can order
      ferromagnetically on quenching from the isotropic phase. Cooling in the absence
      of a magnetic field produces a polydomain sample exhibiting the two opposing
      states of magnetization, oriented parallel to the direction of nematic ordering.
      Cooling in the presence of a magnetic field yields a monodomain sample;
      magnetization can be switched by domain wall movement on reversal of the applied
      magnetic field. The ferromagnetic properties of this dipolar fluid are due to the
      interplay of the nematic elastic interaction (which depends critically on the
      shape of the particles) and the magnetic dipolar interaction. This ferromagnetic
      phase responds to very small magnetic fields and may find use in magneto-optic
      devices. 

PMID- 24336283
TI  - An archaeal origin of eukaryotes supports only two primary domains of life.
AB  - The discovery of the Archaea and the proposal of the three-domains 'universal'
      tree, based on ribosomal RNA and core genes mainly involved in protein
      translation, catalysed new ideas for cellular evolution and eukaryotic origins.
      However, accumulating evidence suggests that the three-domains tree may be
      incorrect: evolutionary trees made using newer methods place eukaryotic core
      genes within the Archaea, supporting hypotheses in which an archaeon participated
      in eukaryotic origins by founding the host lineage for the mitochondrial
      endosymbiont. These results provide support for only two primary domains of life-
      Archaea and Bacteria--because eukaryotes arose through partnership between them.

PMID- 24336285
TI  - Increased insolation threshold for runaway greenhouse processes on Earth-like
      planets.
AB  - The increase in solar luminosity over geological timescales should warm the
      Earth's climate, increasing water evaporation, which will in turn enhance the
      atmospheric greenhouse effect. Above a certain critical insolation, this
      destabilizing greenhouse feedback can 'run away' until the oceans have completely
      evaporated. Through increases in stratospheric humidity, warming may also cause
      evaporative loss of the oceans to space before the runaway greenhouse state
      occurs. The critical insolation thresholds for these processes, however, remain
      uncertain because they have so far been evaluated using one-dimensional models
      that cannot account for the dynamical and cloud feedback effects that are key
      stabilizing features of the Earth's climate. Here we use a three-dimensional
      global climate model to show that the insolation threshold for the runaway
      greenhouse state to occur is about 375 W m(-2), which is significantly higher
      than previously thought. Our model is specifically developed to quantify the
      climate response of Earth-like planets to increased insolation in hot and
      extremely moist atmospheres. In contrast with previous studies, we find that
      clouds have a destabilizing feedback effect on the long-term warming. However,
      subsident, unsaturated regions created by the Hadley circulation have a
      stabilizing effect that is strong enough to shift the runaway greenhouse limit to
      higher values of insolation than are inferred from one-dimensional models.
      Furthermore, because of wavelength-dependent radiative effects, the stratosphere
      remains sufficiently cold and dry to hamper the escape of atmospheric water, even
      at large fluxes. This has strong implications for the possibility of liquid water
      existing on Venus early in its history, and extends the size of the habitable
      zone around other stars. 

PMID- 24336286
TI  - Parvalbumin-expressing basket-cell network plasticity induced by experience
      regulates adult learning.
AB  - Learning and memory processes can be influenced by recent experience, but the
      mechanisms involved are poorly understood. Enhanced plasticity during critical
      periods of early life is linked to differentiating parvalbumin (PV)-interneuron
      networks, suggesting that recent experience may modulate learning by targeting
      the differentiation state of PV neurons in the adult. Here we show that
      environmental enrichment and Pavlovian contextual fear conditioning induce
      opposite, sustained and reversible hippocampal PV-network configurations in adult
      mice. Specifically, enrichment promotes the emergence of large fractions of low
      differentiation (low PV and GAD67 expression) basket cells with low excitatory-to
      inhibitory synaptic-density ratios, whereas fear conditioning leads to large
      fractions of high-differentiation (high PV and GAD67 expression) basket cells
      with high excitatory-to-inhibitory synaptic-density ratios. Pharmacogenetic
      inhibition or activation of PV neurons was sufficient to induce such opposite low
      PV-network or high-PV-network configurations, respectively. The low-PV-network
      configuration enhanced structural synaptic plasticity, and memory consolidation
      and retrieval, whereas these were reduced by the high-PV-network configuration.
      We then show that maze navigation learning induces a hippocampal low-PV-network
      configuration paralleled by enhanced memory and structural synaptic plasticity
      throughout training, followed by a shift to a high-PV-network configuration after
      learning completion. The shift to a low-PV-network configuration specifically
      involved increased vasoactive intestinal polypeptide (VIP)-positive GABAergic
      boutons and synaptic transmission onto PV neurons. Closely comparable low- and
      high-PV-network configurations involving VIP boutons were specifically induced in
      primary motor cortex upon rotarod motor learning. These results uncover a network
      plasticity mechanism induced after learning through VIP-PV microcircuit
      modulation, and involving large, sustained and reversible shifts in the
      configuration of PV basket-cell networks in the adult. This novel form of
      experience-related plasticity in the adult modulates memory consolidation,
      retrieval and learning, and might be harnessed for therapeutic strategies to
      promote cognitive enhancement and neuroprotection. 

PMID- 24336287
TI  - Distinct fibroblast lineages determine dermal architecture in skin development
      and repair.
AB  - Fibroblasts are the major mesenchymal cell type in connective tissue and deposit
      the collagen and elastic fibres of the extracellular matrix (ECM). Even within a
      single tissue, fibroblasts exhibit considerable functional diversity, but it is
      not known whether this reflects the existence of a differentiation hierarchy or
      is a response to different environmental factors. Here we show, using
      transplantation assays and lineage tracing in mice, that the fibroblasts of skin
      connective tissue arise from two distinct lineages. One forms the upper dermis,
      including the dermal papilla that regulates hair growth and the arrector pili
      muscle, which controls piloerection. The other forms the lower dermis, including
      the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the
      preadipocytes and adipocytes of the hypodermis. The upper lineage is required for
      hair follicle formation. In wounded adult skin, the initial wave of dermal repair
      is mediated by the lower lineage and upper dermal fibroblasts are recruited only
      during re-epithelialization. Epidermal beta-catenin activation stimulates the
      expansion of the upper dermal lineage, rendering wounds permissive for hair
      follicle formation. Our findings explain why wounding is linked to formation of
      ECM-rich scar tissue that lacks hair follicles. They also form a platform for
      discovering fibroblast lineages in other tissues and for examining fibroblast
      changes in ageing and disease. 

PMID- 24336288
TI  - Primary cilia are specialized calcium signalling organelles.
AB  - Primary cilia are solitary, non-motile extensions of the centriole found on
      nearly all nucleated eukaryotic cells between cell divisions. Only ~200-300 nm in
      diameter and a few micrometres long, they are separated from the cytoplasm by the
      ciliary neck and basal body. Often called sensory cilia, they are thought to
      receive chemical and mechanical stimuli and initiate specific cellular signal
      transduction pathways. When activated by a ligand, hedgehog pathway proteins,
      such as GLI2 and smoothened (SMO), translocate from the cell into the cilium.
      Mutations in primary ciliary proteins are associated with severe developmental
      defects. The ionic conditions, permeability of the primary cilia membrane, and
      effectiveness of the diffusion barriers between the cilia and cell body are
      unknown. Here we show that cilia are a unique calcium compartment regulated by a
      heteromeric TRP channel, PKD1L1-PKD2L1, in mice and humans. In contrast to the
      hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium
      that are conducted into the cytoplasm, we show that changes in ciliary calcium
      concentration occur without substantially altering global cytoplasmic calcium.
      PKD1L1-PKD2L1 acts as a ciliary calcium channel controlling ciliary calcium
      concentration and thereby modifying SMO-activated GLI2 translocation and GLI1
      expression. 

PMID- 24336291
TI  - Effect of insulin on excitatory synaptic transmission onto dopamine neurons of
      the ventral tegmental area in a mouse model of hyperinsulinemia.
AB  - Obesity has drastically increased over the last few decades. Obesity is
      associated with elevated insulin levels, which can gain access to the brain,
      including into dopamine neurons of the ventral tegmental area (VTA), a brain
      region critical for mediating reward-seeking behavior. Synaptic plasticity of VTA
      dopamine neurons is associated with altered motivation to obtain reinforcing
      substances such as food and drugs of abuse. Under physiological circumstances,
      insulin in the VTA can suppress excitatory synaptic transmission onto VTA
      dopamine neurons and reduce aspects of palatable feeding behavior. However, it is
      unknown how insulin modulates excitatory synaptic transmission in pathological
      circumstances such as hyperinsulinemia. Using patch-clamp electrophysiology, we
      demonstrate that, in a hyperinsulinemic mouse model, insulin has reduced capacity
      to cause a synaptic depression of VTA dopamine neurons, although both low
      frequency stimulation-induced long-term depression and cannabinoid-induced
      depression were normal. These results suggest that insulin action in the VTA
      during pathological hyperinsulinemia is disrupted and may lead to increased
      feeding behavior. 

PMID- 24336289
TI  - Direct recording and molecular identification of the calcium channel of primary
      cilia.
AB  - A primary cilium is a solitary, slender, non-motile protuberance of structured
      microtubules (9+0) enclosed by plasma membrane. Housing components of the cell
      division apparatus between cell divisions, primary cilia also serve as
      specialized compartments for calcium signalling and hedgehog signalling pathways.
      Specialized sensory cilia such as retinal photoreceptors and olfactory cilia use
      diverse ion channels. An ion current has been measured from primary cilia of
      kidney cells, but the responsible genes have not been identified. The polycystin
      proteins (PC and PKD), identified in linkage studies of polycystic kidney
      disease, are candidate channels divided into two structural classes: 11
      transmembrane proteins (PKD1, PKD1L1 and PKD1L2) remarkable for a large
      extracellular amino terminus of putative cell adhesion domains and a G-protein
      coupled receptor proteolytic site, and the 6-transmembrane channel proteins
      (PKD2, PKD2L1 and PKD2L2; TRPPs). Evidence indicates that the PKD1 proteins
      associate with the PKD2 proteins via coiled-coil domains. Here we use a
      transgenic mouse in which only cilia express a fluorophore and use it to record
      directly from primary cilia, and demonstrate that PKD1L1 and PKD2L1 form ion
      channels at high densities in several cell types. In conjunction with an
      accompanying manuscript, we show that the PKD1L1-PKD2L1 heteromeric channel
      establishes the cilia as a unique calcium compartment within cells that modulates
      established hedgehog pathways. 

PMID- 24336292
TI  - A hyperpolarized equilibrium for magnetic resonance.
AB  - Nuclear magnetic resonance spectroscopy and imaging (MRI) play an indispensable
      role in science and healthcare but use only a tiny fraction of their potential.
      No more than ~10 p.p.m. of all 1H nuclei are effectively detected in a 3-Tesla
      clinical MRI system. Thus, a vast array of new applications lays dormant,
      awaiting improved sensitivity. Here we demonstrate the continuous polarization of
      small molecules in solution to a level that cannot be achieved in a viable
      magnet. The magnetization does not decay and is effectively reinitialized within
      seconds after being measured. This effect depends on the long-lived, entangled
      spin-order of parahydrogen and an exchange reaction in a low magnetic field of 10
      3 Tesla. We demonstrate the potential of this method by fast MRI and envision the
      catalysis of new applications such as cancer screening or indeed low-field MRI
      for routine use and remote application.

PMID- 24336293
TI  - Traumatic endophthalmitis caused by Shewanella putrefaciens associated with an
      open globe fishhook injury.

PMID- 24336294
TI  - Objective evaluation of refractive data and astigmatism: quantification and
      analysis.
AB  - The aim of this study was to present methods to improve the analysis of
      refractive data. A comparison of methods is used to analyse refractive powers
      using individual powers and aggregate data. Equations are also developed for the
      representation of the average power of a lens or refractive data as a univariate
      measure, which includes spherical, coma, and/or other aberrations. The equations
      provide a precise representation of refractive power, which is useful for
      comparing individual and aggregate data. Average lens power in the principal
      meridian can be adequately computed as can the average lens power through
      orthogonal and oblique meridians, providing a good univariate representation of
      astigmatism and refractive power. Although these formulae are perhaps not as easy
      to use as, for example, the spherical equivalent, they are more precise and
      superior in principle involving fewer approximations and are not subject to
      systematic bias. These effects are of significance when dealing with high-powered
      lenses such as intraocular lenses or the cornea. They need to be taken into
      account particularly for calculations of intraocular lens power, toric
      intraocular lenses, and cornea refractive surgery, especially if outcomes are to
      be improved. Such issues are of particular importance when dealing with aggregate
      data and determining statistical significance of treatment effects. 

PMID- 24336295
TI  - Analysis of long-term outcomes for combined pars plana vitrectomy (PPV) and
      glaucoma tube shunt surgery in eyes with advanced glaucoma.
AB  - PURPOSE: To analyze 12- and 24-month visual acuity, intraocular pressure, and
      complications associated with combined pars plana vitrectomy (PPV) and glaucoma
      tube shunt placement in eyes with glaucoma. PATIENTS AND METHODS: A retrospective
      chart review was performed of patients with advanced glaucoma who underwent
      combined PPV and tube shunt surgery from 2006 to 2010. A minimum of 12 months of
      follow-up was required for their inclusion in the study. Visual acuity,
      intraocular pressure, complications, and number of glaucoma medications at 1 and
      2 years postoperatively were analyzed. RESULTS: Twenty-eight eyes met the
      inclusion and exclusion criteria. Baseline visual acuity was 20/200 or worse in
      14/28 eyes (50.0%) and 20/40 or better in 2/28 eyes (7.1%). Visual acuity
      remained 20/200 or worse in 50.0% (P=0.921) and 44.4% (P=0.973) of eyes after 1
      and 2 years postoperatively, respectively. At baseline, the mean intraocular
      pressure was 30.4 mm Hg. There was significant improvement in mean IOP at 1 year
      (14.7 mm Hg, P=0.001) and at 2 years (15.2 mm Hg, P=0.001) postoperatively.
      Baseline number of glaucoma medications averaged 3.0+/-1.09 (SD), and improved to
      1.8+/-1.28 (SD) at 1 year (P=0.0002) and to 1.4+/-1.33 at 2 years (P<0.0001)
      postoperatively. CONCLUSION: In this retrospective interventional case series,
      surgical management of advanced glaucoma with a combination of PPV and glaucoma
      tube shunt resulted in significantly reduced IOP and glaucoma medications at 1
      and 2 years postoperatively.

PMID- 24336296
TI  - Visual regulation of refractive development: insights from animal studies.
AB  - Investigations employing animal models have demonstrated that ocular growth and
      refractive development are regulated by visual feedback. In particular, lens
      compensation experiments in which treatment lenses are used to manipulate the
      eye's effective refractive state have shown that emmetropization is actively
      regulated by signals produced by optical defocus. These observations in animals
      are significant because they indicate that it should be possible to use optical
      treatment strategies to influence refractive development in children,
      specifically to slow the rate of myopia progression. This review highlights some
      of the optical performance properties of the vision-dependent mechanisms that
      regulate refractive error development, especially those that are likely to
      influence the efficacy of optical treatment strategies for myopia. In this
      respect, the results from animal studies have been very consistent across
      species; however, to facilitate extrapolation to clinical settings, results are
      presented primarily for nonhuman primates. In agreement with preliminary clinical
      trials, the experimental data show that imposed myopic defocus can slow ocular
      growth and that treatment strategies that influence visual signals over a large
      area of the retina are likely to be most effective. 

PMID- 24336298
TI  - Anterior vitreous displacement of the intravitreal dexamethasone implant
      (Ozurdex).

PMID- 24336297
TI  - Intravitreal bevacizumab (Avastin) versus triamcinolone (Volon A) for treatment
      of diabetic macular edema: one-year results.
AB  - PURPOSE: The objective was to compare retinal morphology and function following
      intravitreal injections of bevacizumab (Avastin) or triamcinolone (Volon A) in
      patients with early diabetic macular edema (DME). PATIENTS AND METHODS: The study
      was planned as a randomized, prospective, interventional clinical trial. A total
      of 30 diabetic patients with treatment-naive, clinically significant macular
      edema were included in this study and randomized to two equal groups. One group
      initially received three injections of 2.5 mg bevacizumab in monthly intervals.
      The second group received a single injection of 8 mg triamcinolone, followed by
      two sham interventions. Functional and anatomic results were evaluated monthly
      using ETDRS vision charts and spectral-domain optical coherence tomography.
      According to the study protocol, retreatment after 3 months was dependent on
      functional and anatomic outcome in a PRN regimen. RESULTS: Baseline best
      corrected visual acuity (BCVA) was 0.30 logMAR and central retinal subfield
      thickness (CSRT) was 505 MUm in the bevacizumab group and 0.32 logMAR and 490 MUm
      CSRT in the triamcinolone group. After 3 months, BCVA improved to 0.23 logMAR
      (bevacizumab) and 358 MUm CRST and 0.26 logMAR (triamcinolone) and 308 MUm CSRT.
      After 12 months, BCVA further recovered in the bevacizumab group (0.18 logMAR)
      but slightly decreased in the triamcinolone group (0.36 logMAR). CONCLUSION:
      Intravitreal bevacizumab and triamcinolone are both equally effective in reducing
      CSRT in early DME. After 6 months, rehabilitation of vision was comparable in
      both treatment arms, whereas at the final follow-up at month 12, BCVA was
      superior in the bevacizumab than in the triamcinolone sample. This may be related
      to cataract development following steroid treatment, as well as to substance
      specific mechanisms within the angiogenic versus the inflammatory cascade.

PMID- 24336299
TI  - Response to Dr Yeo.

PMID- 24336300
TI  - Reply: Intensive cataract training: a novel approach.

PMID- 24336301
TI  - Large and fast reversible Li-ion storages in Fe2O3-graphene sheet-on-sheet
      sandwich-like nanocomposites.
AB  - Fe2O3 nanosheets and nanoparticles are grown on graphene by simply varying
      reaction solvents in a facile solvothermal/hydrothermal preparation. Fe2O3
      nanosheets are uniformly dispersed among graphene nanosheets, forming a unique
      sheet-on-sheet nanostructure. Due to the structure affinity between two types of
      two dimensional nanostructures, graphene nanosheets are separated better by Fe2O3
      nanosheets compared to nanoparticles and their agglomeration is largely
      prevented. A large surface area of 173.9 m(2) g(-1) is observed for Fe2O3
      graphene sheet-on-sheet composite, which is more than two times as large as that
      of Fe2O3-graphene particle-on-sheet composite (81.5 m(2) g(-1)). The sheet-on
      sheet composite is found to be better suitable as an anode for Li-ion battery. A
      high reversible capacity of 662.4 mAh g(-1) can be observed after 100 cycles at
      1000 mA g(-1). The substantially improved cycling performance is ascribed to the
      unique structure affinity between Fe2O3 nanosheets and graphene nanosheets, thus
      offering complementary property improvement. 

PMID- 24336302
TI  - The symbolic and the material in tobacco control: both matter.

PMID- 24336304
TI  - The Brady Bunch? New evidence for nominative determinism in patients' health:
      retrospective, population based cohort study.
AB  - OBJECTIVE: To ascertain whether a name can influence a person's health, by
      assessing whether people with the surname "Brady" have an increased prevalence of
      bradycardia. DESIGN: Retrospective, population based cohort study. SETTING: One
      university teaching hospital in Dublin, Ireland. PARTICIPANTS: People with the
      surname "Brady" in Dublin, determined through use of an online telephone
      directory. MAIN OUTCOME MEASURE: Prevalence of participants who had pacemakers
      inserted for bradycardia between 1 January 2007 and 28 February 2013. RESULTS:
      579 (0.36%) of 161,967 people who were listed on the Dublin telephone listings
      had the surname "Brady." The proportion of pacemaker recipients was significantly
      higher among Bradys (n=8, 1.38%) than among non-Bradys (n=991, 0.61%; P=0.03).
      The unadjusted odds ratio (95% confidence interval) for pacemaker implantation
      among individuals with the surname Brady compared with individuals with other
      surnames was 2.27 (1.13 to 4.57). CONCLUSIONS: Patients named Brady are at
      increased risk of needing pacemaker implantation compared with the general
      population. This finding shows a potential role for nominative determinism in
      health.

PMID- 24336305
TI  - "Compulsive plague! pain without end!" How Richard Wagner played out his migraine
      in the opera Siegfried.

PMID- 24336306
TI  - From the Ottomans to the present day: 150 years of Scottish medical charity in
      the Holy Land.

PMID- 24336307
TI  - Were James Bond's drinks shaken because of alcohol induced tremor?
AB  - OBJECTIVE: To quantify James Bond's consumption of alcohol as detailed in the
      series of novels by Ian Fleming. DESIGN: Retrospective literature review.
      SETTING: The study authors' homes, in a comfy chair. PARTICIPANTS: Commander
      James Bond, 007; Mr Ian Lancaster Fleming. MAIN OUTCOME MEASURES: Weekly alcohol
      consumption by Commander Bond. METHODS: All 14 James Bond books were read by two
      of the authors. Contemporaneous notes were taken detailing every alcoholic drink
      taken. Predefined alcohol unit levels were used to calculate consumption. Days
      when Bond was unable to consume alcohol (such as through incarceration) were
      noted. RESULTS: After exclusion of days when Bond was unable to drink, his weekly
      alcohol consumption was 92 units a week, over four times the recommended amount.
      His maximum daily consumption was 49.8 units. He had only 12.5 alcohol free days
      out of 87.5 days on which he was able to drink. CONCLUSIONS: James Bond's level
      of alcohol intake puts him at high risk of multiple alcohol related diseases and
      an early death. The level of functioning as displayed in the books is
      inconsistent with the physical, mental, and indeed sexual functioning expected
      from someone drinking this much alcohol. We advise an immediate referral for
      further assessment and treatment, a reduction in alcohol consumption to safe
      levels, and suspect that the famous catchphrase "shaken, not stirred" could be
      because of alcohol induced tremor affecting his hands.

PMID- 24336309
TI  - Renewing US medical students' interest in primary care: bridging the role model
      gap.

PMID- 24336308
TI  - Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and
      Harmful): narrative synthesis.
AB  - OBJECTIVE: To review the beneficial and harmful effects of laughter. DESIGN:
      Narrative synthesis. DATA SOURCES AND REVIEW METHODS: We searched Medline (1946
      to June 2013) and Embase (1974 to June 2013) for reports of benefits or harms
      from laughter in humans, and counted the number of papers in each category.
      RESULTS: Benefits of laughter include reduced anger, anxiety, depression, and
      stress; reduced tension (psychological and cardiovascular); increased pain
      threshold; reduced risk of myocardial infarction (presumably requiring hearty
      laughter); improved lung function; increased energy expenditure; and reduced
      blood glucose concentration. However, laughter is no joke-dangers include
      syncope, cardiac and oesophageal rupture, and protrusion of abdominal hernias
      (from side splitting laughter or laughing fit to burst), asthma attacks,
      interlobular emphysema, cataplexy, headaches, jaw dislocation, and stress
      incontinence (from laughing like a drain). Infectious laughter can disseminate
      real infection, which is potentially preventable by laughing up your sleeve. As a
      side effect of our search for side effects, we also list pathological causes of
      laughter, among them epilepsy (gelastic seizures), cerebral tumours, Angelman's
      syndrome, strokes, multiple sclerosis, and amyotrophic lateral sclerosis or motor
      neuron disease. CONCLUSIONS: Laughter is not purely beneficial. The harms it can
      cause are immediate and dose related, the risks being highest for Homeric
      (uncontrollable) laughter. The benefit-harm balance is probably favourable. It
      remains to be seen whether sick jokes make you ill or jokes in bad taste cause
      dysgeusia, and whether our views on comedians stand up to further scrutiny.

PMID- 24336310
TI  - Republished: recent advances in autoimmune pancreatitis: type 1 and type 2.
AB  - Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterised
      clinically by frequent presentation with obstructive jaundice, histologically by
      a lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic
      response to steroids. When so defined, AIP can be sub-classified into two
      subtypes, 1 and 2. Recent international consensus diagnostic criteria for AIP
      have been developed for diagnosis of both forms of AIP. Type 1 AIP is the
      pancreatic manifestation of a multiorgan disease, recently named IgG4-related
      disease. Little is known about the pathogenesis of either form of AIP. Despite
      frequent association of type 1 AIP with elevated serum IgG4 levels and
      infiltration with IgG4-positive plasma cells, it is unlikely that IgG4 plays a
      pathogenic role in AIP. Type 1 AIP responds to steroids, but there needs to be
      consensus on treatment regimens for induction and therapeutic end points.
      Relapses are common, but can be reduced by long-term use of low-dose steroids.
      Recent reports suggest that immunomodulators (azathioprine, 6-mercaptopurine and
      mycophenolate mofetil), as well biological agents (the antibody to CD20,
      rituximab) may have a role in maintaining remission in relapsing type 1 AIP.
      Future studies should clarify the best management options for treatment of
      relapses and maintenance of remission. Type 2 AIP is a pancreas-specific disorder
      not associated with IgG4. It presents in younger individuals equally with
      obstructive jaundice and pancreatitis. The inflammatory process responds to
      steroid therapy; relapses are uncommon. The clinical spectrum and long-term
      outcomes of medically treated type 2 AIP are still being evaluated. 

PMID- 24336311
TI  - Republished: recent advances in the epidemiology, diagnosis and treatment of
      endomyocardial fibrosis in Africa.
AB  - Endomyocardial fibrosis (EMF) continues to be an important and disabling disease
      in many parts of Africa, although its prevalence has declined in some parts of
      the continent. Increased access to medical care in general and increased
      availability of echocardiography in some parts of the continent have led to
      recognition of the disease in areas in which the disease had not been previously
      reported, and this has given new insights into its natural history. However, the
      early manifestations of EMF continue to elude clinicians and researchers, and no
      progress has been made in defining its aetiology. Advances have, however, been
      made in establishing the epidemiology and improving clinical diagnosis and
      management, through modern medical therapy and improved surgical techniques.
      Research is still required to define clinical, biological and echocardiographic
      markers of early stages of EMF, so that advances in the knowledge of its
      pathogenesis and pathophysiology can be made. This will hopefully determine
      preventive measures and avoid the burden of this debilitating condition in this
      continent. 

PMID- 24336312
TI  - Meetings with teams.

PMID- 24336314
TI  - Hybrid Model Predictive Control for Optimizing Gestational Weight Gain Behavioral
      Interventions.
AB  - Excessive gestational weight gain (GWG) represents a major public health issue.
      In this paper, we pursue a control engineering approach to the problem by
      applying model predictive control (MPC) algorithms to act as decision policies in
      the intervention for assigning optimal intervention dosages. The intervention
      components consist of education, behavioral modification and active learning. The
      categorical nature of the intervention dosage assignment problem dictates the
      need for hybrid model predictive control (HMPC) schemes, ultimately leading to
      improved outcomes. The goal is to design a controller that generates an
      intervention dosage sequence which improves a participant's healthy eating
      behavior and physical activity to better control GWG. An improved formulation of
      self-regulation is also presented through the use of Internal Model Control
      (IMC), allowing greater flexibility in describing self-regulatory behavior.
      Simulation results illustrate the basic workings of the model and demonstrate the
      benefits of hybrid predictive control for optimized GWG adaptive interventions.

PMID- 24336313
TI  - Mandibular fracture patterns consistent with posterior maxillary fractures
      involving the posterior maxillary sinus, pterygoid plate or both: CT
      characteristics.
AB  - OBJECTIVES: The aim of this study was to determine the incidence of posterior
      maxillary fractures involving the posterior maxillary sinus wall, pterygoid plate
      or both, unrelated to major midface fractures in patients with mandibular
      fractures, and to characterize associated fractures. METHODS: A CT study was
      performed in patients with mandibular fractures to identify posterior maxillary
      fractures. Patients aged under 16 years, those with mandibular fractures
      involving only dentoalveolar components and those with concurrent major midfacial
      fractures were excluded. RESULTS: 13 (6.7%) of 194 patients with mandibular
      fractures also had posterior maxillary fractures (case group). The injury pattern
      correlated with the external force directed to the lateral side of the mandible
      (p < 0.001), alcohol consumption (p = 0.049), the presence of multifocal
      fractures (p = 0.002) and the fracture regions in the symphysis/parasymphysis (p
      = 0.001) and the angle/ramus (p = 0.001). No significant difference between the
      case and non-case groups was seen for age, sex or cause of trauma. Non-displaced
      fractures in the ipsilateral posterior mandible occurred with significant
      frequency (p = 0.001) when the posterior maxillary fractures involved only the
      sinus. CONCLUSIONS: Mandibular fractures accompanied by posterior maxillary
      fractures are not rare. The finding of a unilateral posterior maxillary fracture
      on CT may aid the efficient radiological examination of the mandible based on
      possible patterns of associated fractures, as follows: in the ipsilateral
      posterior region as a direct fracture when the impact is a medially directed
      force, and in the symphysis/parasymphysis or contralateral condylar neck as an
      indirect fracture.

PMID- 24336315
TI  - Plasma stable, pH-sensitive fusogenic polymer-modified liposomes: A promising
      carrier for mitoxantrone.
AB  - pH-sensitive liposomes are designed to undergo acid-triggered destabilization. In
      the present study, we prepared polymer-modified, plasma stable, pH-sensitive
      fusogenic mitoxantrone liposomes to increase efficacy and selectivity on cancer
      cell lines. Conventional liposomes were prepared using cholesterol and
      dipalmitoyl-sn-glycero-3-phosphatidylethanolamine.
      Dioleoylphosphatidylethanolamine and a cholesteryl derivative,
      poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co
      PDMAEMA), were used for the preparation of pH-sensitive fusogenic liposomes.
      Using polyethylene glycol (PEG)-poly(monomethylitaconate)-CholC6 (PEG-PMMI
      CholC6) copolymers instead of cholesterol introduced pH-sensitive and plasma
      stability properties simultaneously in prepared liposomes. All formulations were
      prepared by thin film hydration method and subsequently, pH-sensitivity and
      stability in human serum were evaluated. The ability of pH-sensitive fusogenic
      liposomes to enhance the mitoxantrone cytotoxicity and selectivity in cancerous
      cell lines was assessed in vitro compared to normal cell line using human breast
      cancer cell line (MCF-7), human prostate cancer cell line (PC-3), and human
      umbilical vein endothelial cells line. Results revealed that both PMMI-co-PDMAEMA
      and PEG-PMMI-CholC6-based formulations showed pH-sensitive property and were
      found to rapidly release mitoxantrone under mildly acidic conditions.
      Nevertheless, only the PEG-PMMI-CholC6-based liposomes preserved pH-sensitivity
      after incubation in plasma. Mitoxantrone loaded-pH-sensitive fusogenic liposomes
      exhibited a higher cytotoxicity than the control conventional liposomes on MCF-7
      and PC-3 cell lines. On the contrary, both pH-sensitive fusogenic liposomes
      showed lower cytotoxic effect on human umbilical vein endothelial cell line.
      Plasma stable, pH-sensitive fusogenic liposomes are promising carriers for
      enhancing the efficiency and selectivity, besides reduction of the side effects
      of anticancer agents.

PMID- 24336316
TI  - Fe-catalyzed growth of one-dimensional alpha-Si3N4 nanostructures and their
      cathodoluminescence properties.
AB  - Preparation of nanomaterials with various morphologies and exploiting their novel
      physical properties are of vital importance in nanoscientific field. Similarly to
      the III-N compound semiconductors, Si3N4 nanostructures also could be potentially
      used for making optoelectronic devices. In this paper, we report on an improved
      Fe-catalyzed chemical vapour deposition method for synthesizing ultra-long alpha
      Si3N4 nanobelts along with a few nanowires and nanobranches on a carbon felt
      substrate. The ultra-long alpha-Si3N4 nanobelts grew via a combined VLS-base and
      nanobranches via a combined double-stage VLS-base and VS-tip mechanism, as well
      as nanowires via VLS-tip mechanism. The three individual nanostructures showed
      variant optical properties as revealed by a cathodoluminescence spectroscopy. A
      single alpha-Si3N4 nanobelt or nanobranch gave a strong UV-blue emission band as
      well as a broad red emission, whereas a single alpha-Si3N4 nanowire exhibited
      only a broad UV-blue emission. The results reported would be useful in developing
      new photoelectric nanodevices with tailorable or tunable properties. 

PMID- 24336317
TI  - Genome-wide localization of small molecules.
AB  - A vast number of small-molecule ligands, including therapeutic drugs under
      development and in clinical use, elicit their effects by binding specific
      proteins associated with the genome. An ability to map the direct interactions of
      a chemical entity with chromatin genome-wide could provide important insights
      into chemical perturbation of cellular function. Here we describe a method that
      couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq)
      to identify the sites bound by small chemical molecules throughout the human
      genome. We show how Chem-seq can be combined with ChIP-seq to gain unique
      insights into the interaction of drugs with their target proteins throughout the
      genome of tumor cells. These methods will be broadly useful to enhance
      understanding of therapeutic action and to characterize the specificity of
      chemical entities that interact with DNA or genome-associated proteins. 

PMID- 24336318
TI  - Reduced local mutation density in regulatory DNA of cancer genomes is linked to
      DNA repair.
AB  - Carcinogenesis and neoplastic progression are mediated by the accumulation of
      somatic mutations. Here we report that the local density of somatic mutations in
      cancer genomes is highly reduced specifically in accessible regulatory DNA
      defined by DNase I hypersensitive sites. This reduction is independent of any
      known factors influencing somatic mutation density and is observed in diverse
      cancer types, suggesting a general mechanism. By analyzing individual cancer
      genomes, we show that the reduced local mutation density within regulatory DNA is
      linked to intact global genome repair machinery, with nearly complete abrogation
      of the hypomutation phenomenon in individual cancers that possess mutations in
      components of the nucleotide excision repair system. Together, our results
      connect chromatin structure, gene regulation and cancer-associated somatic
      mutation. 

PMID- 24336319
TI  - Enhancing thermoelectric properties of organic composites through hierarchical
      nanostructures.
AB  - Organic thermoelectric (TE) materials are very attractive due to easy processing,
      material abundance, and environmentally-benign characteristics, but their
      potential is significantly restricted by the inferior thermoelectric properties.
      In this work, noncovalently functionalized graphene with fullerene by pi-pi
      stacking in a liquid-liquid interface was integrated into poly(3,4
      ethylenedioxythiophene) poly(styrenesulfonate). Graphene helps to improve
      electrical conductivity while fullerene enhances the Seebeck coefficient and
      hinders thermal conductivity, resulting in the synergistic effect on enhancing
      thermoelectric properties. With the integration of nanohybrids, the electrical
      conductivity increased from ~10,000 to ~70,000 S/m, the thermal conductivity
      changed from 0.2 to 2 W.K(-1)m(-1) while the Seebeck coefficient was enhanced by
      around 4-fold. As a result, nanohybrids-based polymer composites demonstrated the
      figure of merit (ZT) as high as 6.7 * 10(-2), indicating an enhancement of more
      than one order of magnitude in comparison to single-phase filler-based polymer
      composites with ZT at the level of 10(-3).

PMID- 24336320
TI  - The synthesis and structure revision of NSC-134754.
AB  - The synthesis of emetine analogue NSC-134754, a potent inhibitor of the HIF
      pathway, has been accomplished and its structure reassigned. The stereochemistry
      of NSC-134754 has been assigned for the first time using X-ray crystallography
      and it has been demonstrated that only one diastereoisomer is active against HIF.

PMID- 24336321
TI  - Prostate Segmentation in CT Images via Spatial-Constrained Transductive Lasso.
AB  - Accurate prostate segmentation in CT images is a significant yet challenging task
      for image guided radiotherapy. In this paper, a novel semi-automated prostate
      segmentation method is presented. Specifically, to segment the prostate in the
      current treatment image, the physician first takes a few seconds to manually
      specify the first and last slices of the prostate in the image space. Then, the
      prostate is segmented automatically by the proposed two steps: (i) The first step
      of prostate-likelihood estimation to predict the prostate likelihood for each
      voxel in the current treatment image, aiming to generate the 3-D prostate
      likelihood map by the proposed Spatial-COnstrained Transductive LassO (SCOTO);
      (ii) The second step of multi-atlases based label fusion to generate the final
      segmentation result by using the prostate shape information obtained from the
      planning and previous treatment images. The experimental result shows that the
      proposed method outperforms several state-of-the-art methods on prostate
      segmentation in a real prostate CT dataset, consisting of 24 patients with 330
      images. Moreover, it is also clinically feasible since our method just requires
      the physician to spend a few seconds on manual specification of the first and
      last slices of the prostate.

PMID- 24336322
TI  - Group well-child care: an analysis of cost.
AB  - OBJECTIVE: To determine if group well-child visits (WCV) can be cost neutral
      compared with individual WCV by varying health care providers, group size, and
      physician salary. METHOD: We created 6 economic models to evaluate the costs of
      WCV: 3 for individual WCV delivered by (1) advanced practice registered nurse
      (APRN), (2) resident, and (3) attending and 3 for group WCV delivered by (4) APRN
      with a nurse and social worker; (5) resident with an attending, nurse, and child
      life specialist; and (6)attending with a nurse. For group WCV, we performed
      sensitivity analyses on group size and duration of provider participation.
      RESULTS: We achieved cost-neutrality at 4 families in the APRN group WCV model;
      at 3, 4, 5, and 6 families in the resident model with 30, 45, 60, and 90 minutes
      of attending supervision, respectively; and at 4 and 5 families in the low and
      high attending salary model, respectively. CONCLUSION: Group WCV can be delivered
      in a cost-neutral manner by optimizing group size and provider participation.

PMID- 24336323
TI  - TNFalpha promotes osteosarcoma progression by maintaining tumor cells in an
      undifferentiated state.
AB  - Chronic inflammation is frequently associated with tumorigenesis in elderly
      people. By contrast, young people without chronic inflammation often develop
      tumors considered independent of chronic inflammation but driven instead by
      mutations. Thus, whether inflammation has a significant role in tumor progression
      in tumors driven by mutations remains largely unknown. Here we show that TNFalpha
      is required for the tumorigenesis of osteosarcoma, the most common tumor in
      children and adolescents. We show that transplantation of AX osteosarcoma cells,
      which harbor mutations driving c-Myc overexpression and Ink4a-deficiency, in wild
      type mice promotes lethal tumorigenesis accompanied by ectopic bone formation and
      multiple metastases, phenotypes seen in osteosarcoma patients. Such tumorigenesis
      was completely abrogated in TNFalpha-deficient mice. AX cells have the capacity
      to undergo osteoblastic differentiation; however, that activity was significantly
      inhibited by TNFalpha treatment, suggesting that TNFalpha maintains AX cells in
      an undifferentiated state. TNFalpha inhibition of AX cell osteoblastic
      differentiation occurred through ERK activation, and a pharmacological TNFalpha
      inhibitor effectively inhibited both AX cell tumorigenesis and increased
      osteoblastic gene expression and increased survival of tumor-bearing mice. Lethal
      tumorigenesis of AX cells was also abrogated in IL-1alpha/IL-1beta doubly
      deficient mice. We found that both TNFalpha and IL-1 maintained AX cells in an
      undifferentiated state via ERK activation. Thus, inflammatory cytokines are
      required to promote tumorigenesis even in mutation-induced tumors, and
      TNFalpha/IL-1 and ERK may represent therapeutic targets for osteosarcoma. 

PMID- 24336324
TI  - Hallmarks of alternative splicing in cancer.
AB  - The immense majority of genes are alternatively spliced and there are many
      isoforms specifically associated with cancer progression and metastasis. The
      splicing pattern of specific isoforms of numerous genes is altered as cells move
      through the oncogenic process of gaining proliferative capacity, acquiring
      angiogenic, invasive, antiapoptotic and survival properties, becoming free from
      growth factor dependence and growth suppression, altering their metabolism to
      cope with hypoxia, enabling them to acquire mechanisms of immune escape, and as
      they move through the epithelial-mesenchymal and mesenchymal-epithelial
      transitions and metastasis. Each of the 'hallmarks of cancer' is associated with
      a switch in splicing, towards a more aggressive invasive cancer phenotype. The
      choice of isoforms is regulated by several factors (signaling molecules, kinases,
      splicing factors) currently being identified systematically by a number of high
      throughput, independent and unbiased methodologies. Splicing factors are de
      regulated in cancer, and in some cases are themselves oncogenes or pseudo
      oncogenes and can contribute to positive feedback loops driving cancer
      progression. Tumour progression may therefore be associated with a coordinated
      splicing control, meaning that there is the potential for a relatively small
      number of splice factors or their regulators to drive multiple oncogenic
      processes. The understanding of how splicing contributes to the various
      phenotypic traits acquired by tumours as they progress and metastasise, and in
      particular how alternative splicing is coordinated, can and is leading to the
      development of a new class of anticancer therapeutics-the alternative-splicing
      inhibitors. 

PMID- 24336325
TI  - LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via
      Hippo signaling cascade.
AB  - Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually
      associated with asbestos exposure and is highly refractory to current therapeutic
      modalities. MMs show frequent activation of a transcriptional coactivator Yes
      associated protein (YAP), which is attributed to the neurofibromatosis type 2
      (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and
      acquisition of a malignant phenotype. However, the whole mechanism of disordered
      YAP activation in MMs has not yet been well clarified. In the present study, we
      investigated various components of the NF2-Hippo pathway, and eventually found
      that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a
      binding partner of large tumor suppressor type 2 (LATS2), which is one of the
      last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was
      independent of the alteration status of other Hippo pathway components, MM cell
      lines with AJUBA inactivation showed a more dephosphorylated (activated) level of
      YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in
      primary MMs, which was associated with YAP constitutive activation. We found that
      AJUBA transduction into MM cells significantly suppressed promoter activities of
      YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably
      canceled by knockdown of LATS2. In connection with these results, transduction of
      AJUBA-expressing lentivirus significantly inhibited the proliferation and
      anchorage-independent growth of the MM cells that harbored ordinary LATS family
      expression. Taken together, our findings indicate that AJUBA negatively regulates
      YAP activity through the LATS family, and inactivation of AJUBA is a novel key
      mechanism in MM cell proliferation. 

PMID- 24336326
TI  - Stem cell origin of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are common hematologic disorders that are
      characterized by decreased blood counts due to ineffective hematopoiesis. MDS is
      considered a 'preleukemic' disorder linked to a significantly elevated risk of
      developing an overt acute leukemia. Cytopenias can be observed in all three
      myeloid lineages suggesting the involvement of multipotent, immature
      hematopoietic cells in the pathophysiology of this disease. Recent studies using
      murine models of MDS as well as primary patient-derived bone marrow samples have
      provided direct evidence that the most immature, self-renewing hematopoietic stem
      cells (HSC), as well as lineage-committed progenitor cells, are critically
      altered in patients with MDS. Besides significant changes in the number and
      distribution of stem as well as immature progenitor cells, genetic and epigenetic
      aberrations have been identified, which confer functional changes to these
      aberrant stem cells, impairing their ability to proliferate and differentiate.
      Most importantly, aberrant stem cells can persist and further expand after
      treatment, even upon transient achievement of clinical complete remission,
      pointing to a critical role of these cells in disease relapse. Ongoing
      preclinical and clinical studies are particularly focusing on the precise
      molecular and functional characterization of aberrant MDS stem cells in response
      to therapy, with the goal to develop stem cell-targeted strategies for therapy
      and disease monitoring that will allow for achievement of longer-lasting
      remissions in MDS. 

PMID- 24336327
TI  - SALL4 is a new target in endometrial cancer.
AB  - Aggressive cancers and embryonic stem (ES) cells share a common gene expression
      signature. Identifying the key factors/pathway(s) within this ES signature
      responsible for the aggressiveness of cancers can lead to a potential cure. In
      this study, we find that SALL4, a gene involved in the maintenance of ES cell
      self-renewal, is aberrantly expressed in 47.7% of primary human endometrial
      cancer samples. It is not expressed in normal or hyperplastic endometrial. More
      importantly, SALL4 expression is positively correlated with worse patient
      survival and aggressive features such as metastasis in endometrial carcinoma.
      Further functional studies have shown that loss of SALL4 inhibits endometrial
      cancer cell growth in vitro and tumorigenicity in vivo, as a result of inhibition
      of cell proliferation and increased apoptosis. In addition, downregulation of
      SALL4 significantly impedes the migration and invasion properties of endometrial
      cancer cells in vitro and their metastatic potential in vivo. Furthermore,
      manipulation of SALL4 expression can affect drug sensitivity of endometrial
      cancer cells to carboplatin. Moreover, we show that SALL4 specifically binds to
      the c-Myc promoter region in endometrial cancer cells. While downregulation of
      SALL4 leads to a decreased expression of c-Myc at both protein and mRNA levels,
      ectopic SALL4 overexpression causes increased c-Myc protein and mRNA expression,
      indicating that c-Myc is one of the SALL4 downstream targets in endometrial
      tumorigenesis. In summary, we are the first to demonstrate that SALL4 has
      functional role(s) in metastasis and drug resistance in aggressive endometrial
      cancer. As a consequence of its functional roles in cancer cell and absence in
      normal tissue, SALL4 is a potential novel therapeutic target for the high-risk
      endometrial cancer patient population. 

PMID- 24336330
TI  - TGF-beta receptor type-2 expression in cancer-associated fibroblasts regulates
      breast cancer cell growth and survival and is a prognostic marker in pre
      menopausal breast cancer.
AB  - Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine with the
      capability to act as tumour suppressor or tumour promoter depending on the
      cellular context. TGF-beta receptor type-2 (TGFBR2) is the ligand-binding
      receptor for all members of the TGF-beta family. Data from mouse model
      experiments demonstrated that loss of Tgfbr2 expression in mammary fibroblasts
      was linked to tumour initiation and metastasis. Using a randomised tamoxifen
      trial cohort including in total 564 invasive breast carcinomas, we examined
      TGFBR2 expression (n=252) and phosphorylation level of downstream target SMAD2
      (pSMAD2) (n=319) in cancer-associated fibroblasts (CAFs) and assessed links to
      clinicopathological markers, prognostic and treatment-predictive values. The
      study revealed that CAF-specific TGFBR2 expression correlated with improved
      recurrence-free survival. Multivariate analysis confirmed CAF-TGFBR2 to be an
      independent prognostic marker (multivariate Cox regression, hazard ratio: 0.534,
      95% (CI): 0.360-0.793, P=0.002). CAF-specific pSMAD2 levels, however, did not
      associate with survival outcome. Experimentally, TGF-beta signalling in
      fibroblasts was modulated using a TGF-beta ligand and inhibitor or through
      lentiviral short hairpin RNA-mediated TGFBR2-specific knockdown. To determine the
      role of fibroblastic TGF-beta pathway on breast cancer cells, we used cell
      contact-dependent cell growth and clonogenicity assays, which showed that
      knockdown of TGFBR2 in CAFs resulted in increased cell growth, proliferation and
      clonogenic survival. Further, in a mouse model transfected CAFs were co-injected
      with MCF7 and tumour weight and proportion was monitored. We found that mouse
      xenograft tumours comprising TGFBR2 knockdown fibroblasts were slightly bigger
      and displayed increased tumour cell capacity. Overall, our data demonstrate that
      fibroblast-related biomarkers possess clinically relevant information and that
      fibroblasts confer effects on breast cancer cell growth and survival. Regulation
      of tumour-stromal cross-talk through fibroblastic TGF-beta pathway may depend on
      fibroblast phenotype, emphasising the importance to characterise tumour
      microenvironment subtypes. 

PMID- 24336329
TI  - MIF4G domain containing protein regulates cell cycle and hepatic carcinogenesis
      by antagonizing CDK2-dependent p27 stability.
AB  - The CDK inhibitor p27(kip1) plays crucial roles in cell cycle regulation and
      cancer progression. Through yeast two-hybrid screening, we identified MIF4G
      domain containing protein (MIF4GD) as a novel binding partner for p27. The
      association of MIF4GD and p27 was verified using immunoprecipitation and
      glutathione S-transferase (GST) pull-down assays. Interaction with MIF4GD led to
      the stabilization of p27 both in the nucleus and in the cytoplasm in
      hepatocellular carcinoma (HCC) cells as a result of suppressed phosphorylation of
      p27 by CDK2 at threonine187. Serum stimulation decreased the levels of MIF4GD and
      p27 simultaneously. In addition, MIF4GD overexpression resulted in increased p27
      levels and reduced cell proliferation, while knockdown of MIF4GD promoted cell
      cycle progression with decreased p27 levels in cells. Furthermore, overexpression
      of MIF4GD reduced colony formation and inhibited xenograft tumor growth in nude
      mice. Finally, we found that both MIF4GD and p27 were expressed at low levels in
      HCC tissues compared to non-cancerous tissues, and that low expression levels of
      MIF4GD and p27 were associated with significantly worse prognosis in HCC
      patients. Our results suggest that MIF4GD is a potential regulator of p27
      dependent cell proliferation in HCC. These findings provide a rational framework
      for the development of potential HCC therapy by targeting the MIF4GD-p27
      interaction. 

PMID- 24336331
TI  - CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF
      kappaB signaling.
AB  - Many solid cancers including pancreatic ductal adenocarcinoma (PDAC) are
      characterized by an extensive stromal reaction that is accompanied by
      infiltrating tumor-associated macrophages (TAMs). The role of TAMs in malignant
      tumors is only partially understood. Previously, we identified the transcription
      factor CUX1 as an important mediator of tumor progression in PDAC. Interestingly,
      we found that CUX1 is highly expressed not only in tumor cells but also in TAMs.
      On the basis of these data, we aimed to elucidate the effects of CUX1 in TAMs in
      vitro and in vivo. We analyzed the effects of CUX1 on cytokine expression using
      overexpression and knockdown strategies. The cytokine regulation by CUX1 was
      further assessed by reporter assays, DNA pulldown experiments and chromatin
      immunoprecipitation. CUX1 expression in TAMs was analyzed in human pancreatic
      cancer tissues and in a genetic mouse model. Immunohistochemical analysis
      revealed strong expression levels of CUX1 in a distinct subset of TAMs in human
      PDAC tissues. Furthermore, its expression increased during tumor progression in a
      genetic mouse model of PDAC. Profiling experiments showed that CUX1 downregulates
      several NF-kappaB-regulated chemokines such as CXCL10, which have been associated
      with M1 polarization and inhibition of angiogenesis and tumor progression. We
      could demonstrate that CUX1 interacts with NF-kappaB p65, leading to reduced
      binding of NF-kappaB p65 to the chemokine promoters. In addition, CUX1 reduces
      acetylation of NF-kappaB p65 at K310 by recruiting HDAC1. Functionally, CUX1
      expression in TAMs antagonizes T-cell attraction and enhances angiogenesis in
      vitro. We identified CUX1 as an important modulator of the TAMs phenotype and
      function by modulating NF-kappaB-dependent cytokines. 

PMID- 24336328
TI  - Protein kinase C and cancer: what we know and what we do not.
AB  - Since their discovery in the late 1970s, protein kinase C (PKC) isozymes
      represent one of the most extensively studied signaling kinases. PKCs signal
      through multiple pathways and control the expression of genes relevant for cell
      cycle progression, tumorigenesis and metastatic dissemination. Despite the vast
      amount of information concerning the mechanisms that control PKC activation and
      function in cellular models, the relevance of individual PKC isozymes in the
      progression of human cancer is still a matter of controversy. Although the
      expression of PKC isozymes is altered in multiple cancer types, the causal
      relationship between such changes and the initiation and progression of the
      disease remains poorly defined. Animal models developed in the last years helped
      to better understand the involvement of individual PKCs in various cancer types
      and in the context of specific oncogenic alterations. Unraveling the enormous
      complexity in the mechanisms by which PKC isozymes have an impact on
      tumorigenesis and metastasis is key for reassessing their potential as
      pharmacological targets for cancer treatment. 

PMID- 24336332
TI  - Attenuated response of L-type calcium current to nitric oxide in atrial
      fibrillation.
AB  - AIM: Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in
      the regulation of cardiac function. Here, we studied the impact of NO signalling
      on calcium influx in human right atrial myocytes and its relation to atrial
      fibrillation (AF). METHODS AND RESULTS: Right atrial appendages (RAAs) were
      obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique
      was used to evaluate endogenous S-nitrosylation of the alpha1C subunit of L-type
      calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was
      similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP)
      on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard
      voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 uM) by 48%, n/N =
      117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble
      guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase
      (PDE)3 with cilostamide (1 uM) enhanced ICa,L to a similar extent as SNAP.
      However, when cAMP was elevated by PDE3 inhibition or beta-adrenoceptor
      stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF,
      the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory
      effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP
      elevation with SNAP was comparable between the SR and AF group. Moreover, the
      expression of PDE3 and soluble guanylate cyclase was not reduced in AF.
      CONCLUSION: NO exerts dual effects on ICa,L in SR with an increase of basal and
      inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated
      ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but
      regulation of PDE3 is lost.

PMID- 24336333
TI  - Response to: 'Comorbidities in a Mexican mestizo cohort with established
      rheumatoid arthritis' by Vega-Morales et al.

PMID- 24336334
TI  - Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid
      arthritis.
AB  - OBJECTIVE: The presence of anti-citrullinated protein antibodies (ACPA) and IgM
      rheumatoid factor (IgM-RF) years before the clinical diagnosis of rheumatoid
      arthritis (RA) suggests they are possibly involved in the pathogenic process
      underlying RA. In this study, we analysed whether anti-carbamylated protein (anti
      CarP) antibodies, a novel autoantibody system against carbamylated proteins, can
      also be detected in healthy individuals before they developed RA. METHODS:
      Multiple sera from asymptomatic blood donors prior to the onset of their RA
      symptoms and sera from age-matched and sex-matched controls were tested for the
      presence of antibodies directed against carbamylated-fetal calf serum (Ca-FCS),
      carbamylated-fibrinogen (Ca-Fib), cyclic citrullinated-peptide 2 and IgM-RF.
      RESULTS: Anti-Ca-FCS and anti-Ca-Fib antibodies were each present in 27% and 38%
      of the last serum samples of blood donors prior to the diagnosis of RA. Both anti
      Ca-FCS and anti-Ca-Fib antibodies could be detected many years before the onset
      of RA. Anti-CarP antibodies as well as ACPA are, on average, detected earlier
      than IgM-RF. CONCLUSIONS: In addition to ACPA and IgM-RF, also the newly
      identified anti-CarP antibodies appear many years before the diagnosis of RA.

PMID- 24336335
TI  - Genetic risk scores and number of autoantibodies in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs)
      are associated with rheumatoid arthritis (RA). Our objective was to examine the
      combined effect of these associated variants, calculated as a cumulative genetic
      risk score (GRS) on RA predisposition, as well as the number of autoantibodies
      (none, one or two present). METHOD: We calculated four GRSs in 4956 patients and
      4983 controls from four European countries. All four scores contained data on 22
      non-HLA-risk SNPs, and three scores also contained HLA-DRB1 genotypes but had
      different HLA typing resolution. Most patients had data on both rheumatoid factor
      (RF) and anti-citrullinated proteins antibodies (ACPA). The GRSs were
      standardised (std.GRS) to account for population heterogeneity. Discrimination
      between patients and controls was examined by receiveroperating characteristics
      curves, and the four std.GRSs were compared across subgroups according to
      autoantibody status. RESULTS: The std.GRS improved its discriminatory ability
      between patients and controls when HLA-DRB1 data of higher resolution were added
      to the combined score. Patients had higher mean std.GRS than controls (p=7.9*10(
      156)), and this score was significantly higher in patients with autoantibodies
      (shown for both RF and ACPA). Mean std.GRS was also higher in those with two
      versus one autoantibody (p=3.7*10(-23)) but was similar in patients without
      autoantibodies and controls (p=0.12). CONCLUSIONS: The GRS was associated with
      the number of autoantibodies and to both RF and ACPA positivity. ACPA play a more
      important role than RF with regards to the genetic risk profile, but
      stratification of patients according to both RF and ACPA may optimise future
      genetic studies.

PMID- 24336336
TI  - Ultrasound-guided synovial biopsy: a safe, well-tolerated and reliable technique
      for obtaining high-quality synovial tissue from both large and small joints in
      early arthritis patients.
AB  - OBJECTIVE: To determine the tolerability, safety and yield of synovial tissue in
      an early arthritis cohort using a minimally invasive, ultrasound (US)-guided,
      synovial biopsy technique in small, medium and large joints. METHODS: 93
      sequential biopsy procedures were assessed from a total of 57 patients (baseline
      and 36 repeat biopsies at 6 months) recruited as part of the 'Pathobiology of
      Early Arthritis Cohort' study. Patients completed a tolerability questionnaire
      prior to and following the synovial biopsy procedure. The synovial biopsy was
      performed under US guidance with US images of the joint recorded prior to each
      procedure. Synovial tissue was harvested for immunohistochemistry and RNA
      extraction. RESULTS: Five different joint sites were biopsied (knee, elbow,
      wrist, metacarpal phalangeal and proximal interphalangeal). No significant
      complications were reported following the procedure. No difference in pain,
      swelling and stiffness of the biopsied joint from before and after the procedure
      was demonstrated. A median of 14 biopsy samples was retrieved from each procedure
      with 93% of biopsy procedures yielding good quality tissue. RNA yield was good in
      all joints and in repeat biopsies. Multivariant analysis demonstrated a
      significantly greater yield of RNA and graded tissue in relation to a high
      prebiopsy, grey-scale synovitis score (0-3, semiquantitative). CONCLUSIONS: A
      minimally invasive approach to synovial tissue harvesting, using US guidance, is
      both safe and well-tolerated by patients. Tissue quality/RNA yield is preserved
      in subsequent biopsies following therapeutic intervention. A high US grey-scale
      synovitis score is a predictor of good quality/quantity of tissue and RNA.

PMID- 24336337
TI  - First-line analysis of the effects of treatment on progression of structural
      changes in knee osteoarthritis over 24 months: data from the osteoarthritis
      initiative progression cohort.
AB  - OBJECTIVE: To determine, using data from participants enrolled in the progression
      cohort of the OAI, the effects of conventional osteoarthritis (OA)
      pharmacological treatment and those of the combination of glucosamine and
      chondroitin sulfate (Glu/CS) on knee structural changes. METHODS: Six hundred
      patients with knee OA were stratified based on whether or not they received for
      24 consecutive months the OA conventional pharmacological treatment and/or
      Glu/CS. The main outcomes were knee structural changes, including the loss of
      joint space width (JSW) and of cartilage volume measured by quantitative MRI.
      RESULTS: Participants reported taking (+) (n=300) or not taking (-) (n=300) OA
      treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores
      (p<0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline.
      In the -analgesic/NSAIDs group, participants taking Glu/CS had significantly
      reduced loss of cartilage volume at 24 months in the medial central plateau
      (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in
      participants with a higher severity of the disease (JSW<=median). In the
      +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of
      cartilage volume in the global plateau at 12 months (p=0.05), and in the central
      plateau at 24 months (p=0.05). These effects occurred in participants with less
      disease severity (JSW>median). By contrast, no significant reduction in JSW was
      found between all groups. CONCLUSIONS: In +analgesic/NSAIDs groups and 
      analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of
      cartilage volume over 24 months in subregions when assessed with qMRI, arguing
      for a disease-modifying effect of Glu/CS which could not be identified by X-rays.

PMID- 24336338
TI  - Baseline levels of soluble interleukin-6 receptor predict clinical remission in
      patients with rheumatoid arthritis treated with tocilizumab: implications for
      molecular targeted therapy.

PMID- 24336339
TI  - Comorbidities in a Mexican mestizo cohort with established rheumatoid arthritis.

PMID- 24336340
TI  - Giant frictional dissipation peaks and charge-density-wave slips at the NbSe2
      surface.
AB  - Understanding nanoscale friction and dissipation is central to nanotechnology.
      The recent detection of the electronic-friction drop caused by the onset of
      superconductivity in Nb by means of an ultrasensitive non-contact pendulum atomic
      force microscope (AFM) raised hopes that a wider variety of mechanical
      dissipation mechanisms become accessible. Here, we report a multiplet of AFM
      dissipation peaks arising a few nanometres above the surface of NbSe2--a layered
      compound exhibiting an incommensurate charge-density wave (CDW). Each peak
      appears at a well-defined tip-surface interaction force of the order of a
      nanonewton, and persists up to 70 K, where the short-range order of CDWs is known
      to disappear. Comparison of the measurements with a theoretical model suggests
      that the peaks are associated with local, tip-induced 2pi phase slips of the CDW,
      and that dissipation maxima arise from hysteretic behaviour of the CDW phase as
      the tip oscillates at specific distances where sharp local slips occur.

PMID- 24336341
TI  - An ion diffusion method for visualising a solid-like water nanofilm.
AB  - A nano-thick solid-like water film on solid surfaces plays an important role in
      various fields, including biology, materials science, atmospheric chemistry,
      catalysis and astrophysics. Visualising the water nanofilm has been a challenge
      due to its dynamic nature and nanoscale thickness. Here we report an ion
      diffusion method to address this problem using a membrane formed with a BSA
      Na2CO3 (BSA, bovine serum albumin) mixture. After a solid-like water nanofilm
      deposits onto the membrane, Na(+) and CO3(2-) ions diffuse into the film to form
      a solid Na2CO3 phase in its place. Consequently, the morphology of the nanofilm
      can be visualised by the space filled by the Na2CO3. Using this method, we
      successfully observed polygon-like, ribbon-like and spot-like nanofilms at 193 K,
      253 K and room temperature, respectively. Our method may provide a tool for
      characterising confined water films ranging from a few nanometres to hundreds of
      nanometres in thickness. 

PMID- 24336342
TI  - Synthesis of polymeric ladders by topochemical polymerization.
AB  - Two polymeric ladders were synthesized by topochemical polymerization. The
      critical assemblies with multiple reactive centers were characterized by single
      crystal X-ray diffraction. Approximately 64% and 70% of the mass of the two
      polymeric ladders can be derived from biomass, respectively. 

PMID- 24336343
TI  - Engineering BmpA as a carrier for surface display of IgG-binding domain on
      Lactococcus lactis.
AB  - Basic membrane protein A (BmpA) is a potential carrier protein for surface
      display of the IgG-binding domain on Lactococcus lactis. We have shown that it
      can increase the adhesion of bacteria to the intestinal cell model by 1.3-fold
      and have improved BmpA-based surface display by engineering the BmpA molecule.
      The bulk of the BmpA molecule was shown to be important in surface display;
      however, limited shortening (variant Bmp1) resulted in a large increase in the
      surface display ability. The closeness of the N- and the C-terminals in the Bmp1
      model and the inefficiency of the spacer suggest that the distance of the
      passenger from the membrane is not of prime importance in surface display. 

PMID- 24336344
TI  - Unbiased estimation of chloroplast number in mesophyll cells: advantage of a
      genuine three-dimensional approach.
AB  - Chloroplast number per cell is a frequently examined quantitative anatomical
      parameter, often estimated by counting chloroplast profiles in two-dimensional
      (2D) sections of mesophyll cells. However, a mesophyll cell is a three
      dimensional (3D) structure and this has to be taken into account when quantifying
      its internal structure. We compared 2D and 3D approaches to chloroplast counting
      from different points of view: (i) in practical measurements of mesophyll cells
      of Norway spruce needles, (ii) in a 3D model of a mesophyll cell with
      chloroplasts, and (iii) using a theoretical analysis. We applied, for the first
      time, the stereological method of an optical disector based on counting
      chloroplasts in stacks of spruce needle optical cross-sections acquired by
      confocal laser-scanning microscopy. This estimate was compared with counting
      chloroplast profiles in 2D sections from the same stacks of sections. Comparing
      practical measurements of mesophyll cells, calculations performed in a 3D model
      of a cell with chloroplasts as well as a theoretical analysis showed that the 2D
      approach yielded biased results, while the underestimation could be up to 10
      fold. We proved that the frequently used method for counting chloroplasts in a
      mesophyll cell by counting their profiles in 2D sections did not give correct
      results. We concluded that the present disector method can be efficiently used
      for unbiased estimation of chloroplast number per mesophyll cell. This should be
      the method of choice, especially in coniferous needles and leaves with mesophyll
      cells with lignified cell walls where maceration methods are difficult or
      impossible to use. 

PMID- 24336345
TI  - Uncovering DCL1-dependent small RNA loci on plant genomes: a structure-based
      approach.
AB  - In plants, Dicer-like 1 (DCL1)-mediated two-step cleavages are essential for the
      processing of microRNA (miRNA) gene products. Interestingly, DCL1 has been
      indicated to be involved in the production of many small RNAs (sRNAs) that cannot
      be classified as canonical miRNAs. However, genomic and functional information on
      the non-miRNA, DCL1-dependent sRNAs is still limited. Here, we propose a
      secondary structure-based approach for identification of the precursors
      containing novel DCL1-dependent sRNA loci. To demonstrate the utility of the
      workflow: first, 5898 DCL1-dependent sRNAs of 20-24 nucleotides were identified
      from the sRNA high-throughput sequencing data sets prepared from rice DCL1 RNA
      interference transgenic lines. Those perfectly mapped to the rice pre-miRNAs
      (precursor microRNAs) were removed. The remaining 5795 sRNAs were then mapped
      onto the rice genome, obtaining 30 902 perfectly matched loci belonging to 2310
      sRNAs. A total of 4631 clusters of sRNA loci were defined for secondary structure
      prediction by using RNAfold. The prediction results generated by two algorithms,
      namely MFE (minimum free energy) and centroid, were manually compared to identify
      the conserved long-stem structures containing DCL1-dependent sRNA loci. For the
      purpose of a case study, a portion of the prediction results was screened
      manually. As a result, 60 clusters displayed great potential for forming featured
      long-stem structures for the generation of DCL1-dependent sRNAs. Together, the
      results indicate that the proposed workflow is applicable for the identification
      of novel DCL1-dependent sRNA loci on plant genomes. 

PMID- 24336346
TI  - Secondhand exposure to vapors from electronic cigarettes.
AB  - INTRODUCTION: Electronic cigarettes (e-cigarettes) are designed to generate
      inhalable nicotine aerosol (vapor). When an e-cigarette user takes a puff, the
      nicotine solution is heated and the vapor is taken into lungs. Although no
      sidestream vapor is generated between puffs, some of the mainstream vapor is
      exhaled by e-cigarette user. The aim of this study was to evaluate the secondhand
      exposure to nicotine and other tobacco-related toxicants from e-cigarettes.
      MATERIALS AND METHODS: We measured selected airborne markers of secondhand
      exposure: nicotine, aerosol particles (PM(2.5)), carbon monoxide, and volatile
      organic compounds (VOCs) in an exposure chamber. We generated e-cigarette vapor
      from 3 various brands of e-cigarette using a smoking machine and controlled
      exposure conditions. We also compared secondhand exposure with e-cigarette vapor
      and tobacco smoke generated by 5 dual users. RESULTS: The study showed that e
      cigarettes are a source of secondhand exposure to nicotine but not to combustion
      toxicants. The air concentrations of nicotine emitted by various brands of e
      cigarettes ranged from 0.82 to 6.23 ug/m(3). The average concentration of
      nicotine resulting from smoking tobacco cigarettes was 10 times higher than from
      e-cigarettes (31.60+/-6.91 vs. 3.32+/-2.49 ug/m(3), respectively; p = .0081).
      CONCLUSIONS: Using an e-cigarette in indoor environments may involuntarily expose
      nonusers to nicotine but not to toxic tobacco-specific combustion products. More
      research is needed to evaluate health consequences of secondhand exposure to
      nicotine, especially among vulnerable populations, including children, pregnant
      women, and people with cardiovascular conditions.

PMID- 24336347
TI  - Awareness of nicotine replacement therapy among South African smokers and their
      interest in using it for smoking cessation when provided for free.
AB  - INTRODUCTION: This study assessed knowledge of South African smokers about
      nicotine replacement therapy (NRT) and their interest in using it for smoking
      cessation if it is provided free. METHODS: The 2007 South African Social
      Attitudes Survey was analyzed for 689 smokers aged >= 16 years. Prevalence of
      receipt of tobacco cessation counseling from a health care professional as well
      as self-reported knowledge about NRT was calculated. Multivariable logistic
      regression was used to assess factors associated with interest in using NRT if
      provided for free. RESULTS: About 26.1% of current smokers reported ever
      receiving tobacco cessation counselling from a health care professional. Although
      67.7% of smokers were aware of NRT, only 3.9% had ever used NRT. However, 77.6%
      of those aware of NRT were interested in using it for smoking cessation if
      offered for free. After adjusting for potential confounders, smokers' interest in
      using NRT was inversely associated with interest in harm-reduction switching to
      snuff (adjusted odds ratio [AOR] = 0.34; 95% confidence interval [CI] = 0.14
      0.80) and also reduced with each unit increase in lifetime duration of smoking
      (AOR = 0.93; 95% CI = 0.88-0.99). Interest in NRT use was higher among
      polytobacco users compared with exclusive cigarette smokers (AOR = 10.21; 95% CI
      = 1.08-96.15) and generally increased with increasing age of smoker. CONCLUSIONS:
      About two-thirds of smokers knew about NRT, and the majority were interested in
      using NRT for smoking cessation if provided free. These findings underscore the
      need to increase awareness of smokers about NRT through mass-media campaigns as
      well as include tobacco dependence treatment as part of the national health
      insurance programs of low- and middle-income countries.

PMID- 24336348
TI  - Comparison of hepatic transcription profiles of locked ribonucleic acid antisense
      oligonucleotides: evidence of distinct pathways contributing to non-target
      mediated toxicity in mice.
AB  - Development of LNA gapmers, antisense oligonucleotides used for efficient
      inhibition of target RNA expression, is limited by non-target mediated
      hepatotoxicity issues. In the present study, we investigated hepatic
      transcription profiles of mice administered non-toxic and toxic LNA gapmers.
      After repeated administration, a toxic LNA gapmer (TS-2), but not a non-toxic LNA
      gapmer (NTS-1), caused hepatocyte necrosis and increased serum alanine
      aminotransferase levels. Microarray data revealed that, in addition to gene
      expression patterns consistent with hepatotoxicity, 17 genes in the clathrin
      mediated endocytosis (CME) pathway were altered in the TS-2 group. TS-2
      significantly down-regulated myosin 1E (Myo1E), which is involved in release of
      clathrin-coated pits from plasma membranes. To map the earliest transcription
      changes associated with LNA gapmer-induced hepatotoxicity, a second microarray
      analysis was performed using NTS-1, TS-2, and a severely toxic LNA gapmer (HTS-3)
      at 8, 16, and 72 h following a single administration in mice. The only
      histopathological change observed was minor hepatic hypertrophy in all LNA groups
      across time points. NTS-1, but not 2 toxic LNA gapmers, increased immune response
      genes at 8 and 16 h but not at 72 h. TS-2 significantly perturbed the CME pathway
      only at 72 h, while Myo1E levels were decreased at all time points. In contrast,
      HTS-3 modulated DNA damage pathway genes at 8 and 16 h and also modulated the CME
      pathway genes (but not Myo1E) at 16 h. Our results may suggest that different
      LNAs modulate distinct transcriptional genes and pathways contributing to non
      target mediated hepatotoxicity in mice.

PMID- 24336349
TI  - Behavioral and genetic correlates of the neural response to infant crying among
      human fathers.
AB  - Although evolution has shaped human infant crying and the corresponding response
      from caregivers, there is marked variation in paternal involvement and caretaking
      behavior, highlighting the importance of understanding the neurobiology
      supporting optimal paternal responses to cries. We explored the neural response
      to infant cries in fathers of children aged 1-2, and its relationship with
      hormone levels, variation in the androgen receptor (AR) gene, parental attitudes
      and parental behavior. Although number of AR CAG trinucleotide repeats was
      positively correlated with neural activity in brain regions important for empathy
      (anterior insula and inferior frontal gyrus), restrictive attitudes were
      inversely correlated with neural activity in these regions and with regions
      involved with emotion regulation (orbitofrontal cortex). Anterior insula activity
      had a non-linear relationship with paternal caregiving, such that fathers with
      intermediate activation were most involved. These results suggest that
      restrictive attitudes may be associated with decreased empathy and emotion
      regulation in response to a child in distress, and that moderate anterior insula
      activity reflects an optimal level of arousal that supports engaged fathering. 

PMID- 24336350
TI  - Magnetization transfer and adiabatic T1rho MRI reveal abnormalities in normal
      appearing white matter of subjects with multiple sclerosis.
AB  - BACKGROUND: Diffuse abnormalities are known to occur within the brain tissue of
      multiple sclerosis (MS) patients that is "normal appearing" on T1-weighted and T2
      weighted magnetic resonance images. OBJECTIVES: With the goal of exploring the
      sensitivity of novel MRI parameters to detect such abnormalities, we implemented
      an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1rho
      and T2rho rotating frame relaxation methods. METHODS: Nine relapsing-remitting MS
      patients and seven healthy controls were recruited. Relaxation parameters were
      measured in a single slice just above the lateral ventricles and approximately
      parallel to the AC-PC line. RESULTS: The MT ratio of regions encompassing the
      normal-appearing white matter (NAWM) was different in MS patients as compared
      with controls (p = 0.043); however, the T1 measured during off-resonance
      irradiation (T1sat) was substantially more sensitive than the MT ratio for
      detecting differences between groups (p = 0.0006). Adiabatic T1rho was
      significantly prolonged in the NAWM of MS patents as compared to controls (by 6%,
      p = 0.026), while no differences were found among groups for T2rho. No
      differences among groups were observed in the cortical gray matter for any
      relaxation parameter. CONCLUSIONS: The results suggest degenerative processes
      occurring in the NAWM of MS, likely not accompanied by significant abnormalities
      in iron content.

PMID- 24336352
TI  - Slowdown in production of treated bed nets damages fight against malaria.

PMID- 24336351
TI  - Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with
      multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is thought to be caused by T-cell mediated
      autoimmune dysfunction. Risk of developing MS is influenced by environmental and
      genetic factors. Modifiable differences in DNA methylation are recognized as
      epigenetic contributors to MS risk and may provide a valuable link between
      environmental exposure and inherited genetic systems. OBJECTIVES AND METHODS: To
      identify methylation changes associated with MS, we performed a genome-wide DNA
      methylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS
      and 28 healthy controls using Illumina 450K methylation arrays. RESULTS: A
      striking differential methylation signal was observed at chr. 6p21, with a peak
      signal at HLA-DRB1. After prioritisation, we identified a panel of 74 CpGs
      associated with MS in this cohort. Most notably we found evidence of a major
      effect CpG island in DRB1 in MS cases (pFDR < 3 * 10(-3)). In addition, we found
      55 non-HLA CpGs that exhibited differential methylation, many of which localise
      to genes previously linked to MS. CONCLUSIONS: Our findings provide the first
      evidence for association of DNA methylation at HLA-DRB1 in relation to MS risk.
      Further studies are now warranted to validate and understand how these findings
      are involved in MS pathology.

PMID- 24336353
TI  - US outlines plan to reduce use of antimicrobials in food production.

PMID- 24336355
TI  - Visible-light-driven water oxidation at a polychromium-oxo-electrodeposited TiO2
      electrode as a new type of earth-abundant photoanode.
AB  - A polychromium-oxo-deposited TiO2 electrode was fabricated as an earth-abundant
      photoanode for visible-light-driven water oxidation by a simple electrochemical
      technique. The photoelectrocatalytic water oxidation could occur based on a
      specific interfacial charge transfer (IFCT) from a Cr(III) to the TiO2 conduction
      band. 

PMID- 24336354
TI  - Rational optimization of conformational effects induced by hydrocarbon staples in
      peptides and their binding interfaces.
AB  - eIF4E is frequently over-expressed in different cancers and causes increased
      translation of oncogenic proteins via deregulated cap-dependent translation.
      Inhibitors of the eIF4E:eIF4G interactions represent an approach that would
      normalize cap-dependent translation. Stapled peptides represent an emerging class
      of therapeutics that can target protein: protein interactions. We present here
      molecular dynamics simulations for a set of rationally designed stapled peptides
      in solution and in complex with eIF4E, supported with biophysical and
      crystallographic data. Clustering of the simulated structures revealed the
      favoured conformational states of the stapled peptides in their bound or free
      forms in solution. Identifying these populations has allowed us to design
      peptides with improved affinities by introducing mutations into the peptide
      sequence to alter their conformational distributions. These studies emphasise the
      effects that engineered mutations have on the conformations of free and bound
      peptides, and illustrate that both states must be considered in efforts to attain
      high affinity binding. 

PMID- 24336356
TI  - A library screening approach identifies naturally occurring RNA sequences for a G
      quadruplex binding ligand.
AB  - An RNA G-quadruplex library was synthesised and screened against kanamycin A as
      the ligand. Naturally occurring G-quadruplex forming sequences that
      differentially bind to kanamycin A were identified and characterized. This
      provides a simple and effective strategy for identification of potential
      intracellular G-quadruplex targets for a ligand. 

PMID- 24336357
TI  - In-SEM Raman microspectroscopy coupled with EDX--a case study of uranium
      reference particles.
AB  - Information about the molecular composition of airborne uranium-bearing particles
      may be useful as an additional tool for nuclear safeguards. In order to combine
      the detection of micrometer-sized particles with the analysis of their molecular
      forms, we used a hybrid system enabling Raman microanalysis in high vacuum inside
      a SEM chamber (SEM-SCA system). The first step involved an automatic scan of a
      sample to detect and save coordinates of uranium particles, along with X-ray
      microanalysis. In the second phase, the detected particles were relocated in a
      white light image and subjected to Raman microanalysis. The consecutive
      measurements by the two beams showed exceptional fragility of uranium particles,
      leading to their ultimate damage and change of uranium oxidation state. We used
      uranium reference particles prepared by hydrolysis of uranium hexafluoride to
      test the reliability of the Raman measurements inside the high vacuum. The
      results achieved by the hybrid system were verified by using a standalone Raman
      microspectrometer. When deposited on exceptionally smooth substrates, uranyl
      fluoride particles smaller than 1000 nm could successfully be analyzed with the
      SEM-SCA system. 

PMID- 24336358
TI  - Drift time-specific collision energies enable deep-coverage data-independent
      acquisition proteomics.
AB  - We present a data-independent acquisition mass spectrometry method,
      ultradefinition (UD) MS(E). This approach utilizes ion mobility drift time
      specific collision-energy profiles to enhance precursor fragmentation efficiency
      over current MS(E) and high-definition (HD) MS(E) data-independent acquisition
      techniques. UDMS(E) provided high reproducibility and substantially improved
      proteome coverage of the HeLa cell proteome compared to previous implementations
      of MS(E), and it also outperformed a state-of-the-art data-dependent acquisition
      workflow. Additionally, we report a software tool, ISOQuant, for processing label
      free quantitative UDMS(E) data. 

PMID- 24336359
TI  - High-resolution mapping of transcription factor binding sites on native
      chromatin.
AB  - Sequence-specific DNA-binding proteins including transcription factors (TFs) are
      key determinants of gene regulation and chromatin architecture. TF profiling is
      commonly carried out by formaldehyde cross-linking and sonication followed by
      chromatin immunoprecipitation (X-ChIP). We describe a method to profile TF
      binding at high resolution without cross-linking. We begin with micrococcal
      nuclease-digested non-cross-linked chromatin and then perform affinity
      purification of TFs and paired-end sequencing. The resulting occupied regions of
      genomes from affinity-purified naturally isolated chromatin (ORGANIC) profiles of
      Saccharomyces cerevisiae Abf1 and Reb1 provide high-resolution maps that are
      accurate, as defined by the presence of known TF consensus motifs in identified
      binding sites, that are not biased toward accessible chromatin and that do not
      require input normalization. We profiled Drosophila melanogaster GAGA factor and
      Pipsqueak to test ORGANIC performance on larger genomes. Our results suggest that
      ORGANIC profiling is a widely applicable high-resolution method for sensitive and
      specific profiling of direct protein-DNA interactions. 

PMID- 24336360
TI  - Plutonium in soils from northeast China and its potential application for
      evaluation of soil erosion.
AB  - Surface and soil core samples from northeast China were analyzed for Pu isotopes.
      The measured (240)Pu/(239)Pu atomic ratios and (239 + 240)Pu/(137)Cs activity
      ratios revealed that the global fallout is the dominant source of Pu and (137)Cs
      at these sites. Migration behavior of Pu varying with land type and human
      activities resulted in different distribution of Pu in surface soils. A sub
      surface maximum followed by exponential decline of (239 + 240)Pu concentrations
      was observed in an undisturbed soil core, with a total (239 + 240)Pu inventory of
      86.9 Bq/m(2) and more than 85% accumulated in 0 ~ 20 cm layers. While only half
      inventory of Pu was obtained in another soil core and no sub-surface maximum
      value occurred. Erosion of topsoil in the site should be the most possible reason
      for the significantly lower Pu inventory, which is also supported by the reported
      (137)Cs profiles. These results demonstrated that Pu could be applied as an ideal
      substitute of (137)Cs for soil erosion study in the future. 

PMID- 24336361
TI  - Draft Genome Sequence of the Opportunistic Marine Pathogen Vibrio harveyi Strain
      E385.
AB  - Vibrio harveyi strain E385 was isolated from a diseased cage-cultured grouper in
      Daya Bay, China. Phylogenetic analysis based on the 16S rRNA gene sequence showed
      similarity with V. harveyi strain BAA-1116. We sequenced the pathogenic strain V.
      harveyi E385 and compared the genome with that of the nonpathogenic strain V.
      harveyi BAA-1116. 

PMID- 24336362
TI  - Complete Genome Sequence of Escherichia Phage Lw1, a New Member of the RB43 Group
      of Pseudo T-Even Bacteriophages.
AB  - RB43-related bacteriophages have a specific genome type that clearly
      distinguishes them from other T4-like viruses. Here, we present the complete
      genome sequence of a new virulent phage, Lw1, isolated as an Escherichia coli
      BL21(DE3) contaminant. Lw1 shares an RB43-like genome organization, but it does
      not contain putative AP2-domain endonuclease genes. 

PMID- 24336363
TI  - Complete Genome of Bacillus megaterium Siphophage Slash.
AB  - The complete annotated genome sequence of Bacillus megaterium bacteriophage Slash
      is described here. Several key features related to morphogenesis,
      replication/recombination, DNA metabolism, and lysis are described. Slash also
      encodes a homolog of SleB, a germination-specific cell wall amidase. 

PMID- 24336364
TI  - Draft Genome Sequence of "Candidatus Halobonum tyrrellensis" Strain G22, Isolated
      from the Hypersaline Waters of Lake Tyrrell, Australia.
AB  - We report the draft 3.675-Mbp genome sequence of "Candidatus Halobonum
      tyrrellensis" strain G22, a novel halophilic archaeon isolated from the surface
      hypersaline waters of Lake Tyrrell, Australia. The availability of the first
      genome from the "Candidatus Halobonum" genus provides a new genomic resource for
      the comparative genomic analysis of halophilic Archaea. 

PMID- 24336365
TI  - Complete Genome Sequence of Campylobacter fetus subsp. testudinum Strain 03-427T.
AB  - Campylobacter fetus subsp. testudinum has been isolated from reptiles and humans.
      This Campylobacter subspecies is genetically distinct from other C. fetus
      subspecies. Here, we present the first whole-genome sequence for this C. fetus
      subspecies. 

PMID- 24336366
TI  - Draft Genome Sequence of Enterococcus sp. Strain HSIEG1, Isolated from the Human
      Small Intestine.
AB  - Enterococcus sp. strain HSIEG1 was isolated from the human small intestine. Its
      draft genome predicts a broad carbohydrate fermentation capability, which matches
      well with the observed physiological characteristics of this strain. This
      metabolic flexibility is expected to be of importance for survival and growth in
      the small intestinal habitat. 

PMID- 24336367
TI  - Draft Genome Sequence of Salmonella enterica subsp. enterica Serotype Saintpaul
      Strain S-70, Isolated from an Aquatic Environment.
AB  - Salmonella is a pathogen of worldwide importance, causing disease in a vast range
      of hosts, including humans. We report the genome sequence of Salmonella enterica
      subsp. enterica serotype Saintpaul strain S-70, isolated from an aquatic
      environment. 

PMID- 24336368
TI  - Draft Genome Sequence of Salmonella enterica subsp. enterica Serotype Oranienburg
      Strain S-76, Isolated from an Aquatic Environment.
AB  - Salmonella is a widespread microorganism and a common causative agent of food
      borne illnesses. Salmonella enterica subsp. enterica serotype Oranienburg is
      highly prevalent in surface water from tropical ecosystems and is not commonly
      related to illnesses. Here, we report the first genome sequence of Salmonella
      Oranienburg strain S-76, isolated from an aquatic environment. 

PMID- 24336369
TI  - Genome Sequence of Salmonella bongori Strain N268-08.

PMID- 24336370
TI  - Complete Genome Sequence of Porcine Encephalomyocarditis Virus Strain BD2.
AB  - Encephalomyocarditis virus (EMCV) causes acute myocarditis in young pigs or
      reproductive failure in sows, and it is divided into two main groups. Here, we
      report the complete genome sequence of EMCV strain BD2, which belongs to group I.

PMID- 24336371
TI  - Draft Genome Sequences of Two Alginate-Overproducing Variants of Pseudomonas
      aeruginosa, PAO1-VE2 and PAO1-VE13.
AB  - The small envelope protein MucE and the sensor kinase KinB are a positive and
      negative alginate regulator, respectively. Here, we announce the draft genome
      sequences of the alginate-overproducing variants Pseudomonas aeruginosa PAO1-VE2
      (PAO1 with constitutive expression of mucE) and PAO1-VE13 (PAO1 with kinB
      inactivated). Both mutants were generated from a transposon mutagenesis screen. 

PMID- 24336372
TI  - Complete Genome Sequence of Streptococcus pneumoniae Strain A026, a Clinical
      Multidrug-Resistant Isolate Carrying Tn2010.
AB  - Streptococcus pneumoniae is a primary cause of bacterial infection in humans.
      Here, we present the complete genome sequence of S. pneumoniae strain A026, which
      is a multidrug-resistant strain isolated from cerebrospinal fluid. 

PMID- 24336373
TI  - High-Quality Draft Genome Sequence of Xanthomonas alfalfae subsp. alfalfae Strain
      CFBP 3836.
AB  - We report the high-quality draft genome sequence of Xanthomonas alfalfae subsp.
      alfalfae strain CFBP 3836, the causal agent of bacterial leaf and stem spot in
      lucerne (Medicago sativa). Comparative genomics will help to decipher the
      mechanisms provoking disease and triggering the defense responses of this
      pathogen of the model legume Medicago truncatula. 

PMID- 24336374
TI  - High-Quality Draft Genome Sequences of Xanthomonas axonopodis pv. glycines
      Strains CFBP 2526 and CFBP 7119.
AB  - We report here the high-quality draft genome sequences of two strains of
      Xanthomonas axonopodis pv. glycines, the causal agent of bacterial pustule on
      soybeans. Comparison of these genomes with those of phylogenetically closely
      related pathovars of Xanthomonas spp. will help to understand the mechanisms
      involved in host specificity and adaptation to host plants. 

PMID- 24336375
TI  - Draft Genome Sequence of Staphylococcus simulans UMC-CNS-990, Isolated from a
      Case of Chronic Bovine Mastitis.
AB  - Coagulase-negative staphylococci are frequently isolated from cases of
      subclinical bovine mastitis. Reported here is a draft genome sequence of
      Staphylococcus simulans UMC-CNS-990, an isolate recovered from a chronic
      intramammary infection of a Holstein cow. Unexpectedly, a cluster of genes
      encoding gas vesicle proteins was found within the 2,755-kb genome. 

PMID- 24336376
TI  - Genome Sequence of an Enterobacter helveticus Strain, 1159/04 (LMG 23733),
      Isolated from Fruit Powder.
AB  - We report the draft genome sequence of Enterobacter helveticus strain LMG 23733,
      isolated from fruit powder. The draft genome assembly for E. helveticus strain
      LMG 23733 has a size of 4,635,476 bp and a G+C content of 55.9%. 

PMID- 24336377
TI  - Draft Genome Sequence of Serratia sp. Strain ATCC 39006, a Model Bacterium for
      Analysis of the Biosynthesis and Regulation of Prodigiosin, a Carbapenem, and Gas
      Vesicles.
AB  - Serratia sp. strain ATCC 39006 is a Gram-negative bacterium and a member of the
      Enterobacteriaceae that produces various bioactive secondary metabolites,
      including the tripyrrole red pigment prodigiosin and the beta-lactam antibiotic 1
      carbapenen-2-em-3-carboxylic acid (a carbapenem). This strain is the only member
      of the Enterobacteriaceae known to naturally produce gas vesicles, as flotation
      organelles. Here we present the genome sequence of this strain, which has served
      as a model for analysis of the biosynthesis and regulation of antibiotic
      production. 

PMID- 24336378
TI  - Draft Genome Sequence of Fusobacterium nucleatum subsp. vincentii ChDC F8,
      Isolated from a Human Subgingival Plaque in the Republic of Korea.
AB  - Fusobacterium nucleatum is a Gram-negative, nonmotile, obligately anaerobic rod
      bacterium which might play an important role in the initiation and progression of
      periodontal diseases. F. nucleatum subsp. vincentii ChDC F8 (KCOM 1231) was
      isolated from a human gingivitis lesion. Here, we report the draft genome
      sequence of the strain. 

PMID- 24336379
TI  - Draft Genome Sequence of Fusobacterium nucleatum subsp. nucleatum ChDC F316,
      Isolated from a Human Peri-implantitis Lesion in the Republic of Korea.
AB  - Fusobacterium nucleatum is a Gram-negative anaerobe and is one of the causative
      agents of periodontal diseases, including peri-implantitis. Fusobacterium
      nucleatum subsp. nucleatum ChDC F316 (KCOM 1322) was isolated from a human peri
      implantitis lesion. Here, we report the draft genome sequence of this strain. 

PMID- 24336380
TI  - Draft Genome Sequence of Fusobacterium nucleatum subsp. animalis ChDC F324,
      Isolated from a Human Subgingival Plaque in the Republic of Korea.
AB  - Five subspecies of Fusobacterium nucleatum have been classified: animalis,
      nucleatum, polymorphum, vincentii, and fusiforme. F. nucleatum subsp. animalis
      ChDC F324 (KCOM 1325) was isolated from a human subgingival plaque in the
      Republic of Korea. Here, we report the draft genome sequence of the strain. 

PMID- 24336381
TI  - Genome Sequence of a Thermophilic Bacillus, Geobacillus thermodenitrificans
      DSM465.
AB  - Geobacillus thermodenitrificans NG80-2 encodes a LadA-mediated alkane degradation
      pathway, while G. thermodenitrificans DSM465 cannot utilize alkanes. Here, we
      report the draft genome sequence of G. thermodenitrificans DSM465, which may help
      reveal the genomic differences between these two strains in regards to the
      biodegradation of alkanes. 

PMID- 24336382
TI  - Full-genome sequence of hibiscus chlorotic ringspot virus from Israel.
AB  - Hibiscus rosa-sinensis is one of the most prevalent ornamental plants grown in
      private and public gardens. Hibiscus chlorotic ringspot virus (HCRSV) is a member
      of the Carmovirus genus, with a positive single-strand RNA that putatively
      encodes seven proteins. The complete genome of the first Israeli isolate of
      HCRSV, HCRSV-IL, comprises 3,908 nucleotides and shows 93% nucleotide sequence
      identity to the Singapore isolate and 87% identity to the Taiwanese isolate. 

PMID- 24336383
TI  - Genome Sequence of Cupriavidus metallidurans Strain H1130, Isolated from an
      Invasive Human Infection.
AB  - Cupriavidus metallidurans H1130 was repeatedly isolated from different blood
      culture sets taken from a patient suffering from significant nosocomial
      septicemia. Here, we announce the H1130 genome sequence for use in comparative
      analyses and for exploring the adaptation and pathogenic potential of this
      bacterium. 

PMID- 24336384
TI  - Complete Genome Sequence of the Campylobacter coli Clinical Isolate 15-537360.
AB  - Campylobacter coli strain 15-537360 was originally isolated in 2001 from a 42
      year-old patient with gastroenteritis. Here, we report its complete genome
      sequence, which comprises a 1.7-Mbp chromosome and a 29-kbp conjugative cryptic
      plasmid. This is the first complete genome sequence of a clinical isolate of C.
      coli. 

PMID- 24336385
TI  - Single versus multiple-family intervention in childhood overweight--Finnmark
      Activity School: a randomised trial.
AB  - OBJECTIVE: To compare a new comprehensive lifestyle programme performed in groups
      of families with overweight (included obese) children with a more conventional
      single-family programme. The study design and interim anthropometrical results
      after 12 months are presented. DESIGN: Altogether 97 overweight and obese
      children aged 6-12 years with body mass index (BMI) corresponding to cut-off
      point >= 27.5 in adults were included. Study participants were randomised to
      multiple-family intervention (MUFI) or single-family intervention (SIFI) in a
      parallel design. MUFI comprised a 3-day inpatient programme at the hospital with
      other families and a multidisciplinary team, follow-up visits in their hometown
      individually and in groups, organised physical activity twice weekly and a 4-day
      family camp after 6 months. SIFI comprised individual counselling by paediatric
      nurse, paediatric consultant and nutritionist at the hospital and follow-up by
      public health nurse in the community. Solution focused approach was applied in
      both interventions. Primary outcome measures were change in BMI kg/m(2) and BMI
      SD score (BMI SDS). RESULTS: BMI increased by 0.37 units in the MUFI compared to
      0.77 units in the SIFI (p=0.18). BMI SDS decreased by 0.16 units in the MUFI
      group compared to 0.07 units in the SIFI group (p=0.07). Secondary endpoint waist
      circumference decreased 0.94 cm in the multiple-family group and increased 0.95
      cm in the single-family group, p=0.04. CONCLUSIONS: Interim analysis after 12
      months showed no between-group difference in terms of BMI or BMI SDS. The MUFI
      group had a significant decrease in waist circumference compared to the SIFI
      group. THE TRIAL IS REGISTERED: at http://www.clinicaltrials.gov (NCT00872807).

PMID- 24336386
TI  - Vitamin D receptor gene polymorphisms and the risk of rickets among Asians: a
      meta-analysis.
AB  - AIMS: To evaluate the association between vitamin D receptor (VDR) gene
      polymorphisms and the risk of rickets among Asians. METHODS: Eligible studies
      were included in our meta-analysis by searching PubMed, Embase, Cochrane and
      China National Knowledge Infrastructure databases according to a predefined
      criteria. A random effects model was used to calculate the combined ORs and its
      corresponding 95% CI. RESULTS: 16 studies were recruited for the analysis of the
      association between VDR BsmI (rs1544410), TaqI (rs731236), FokI (rs2228570) and
      ApaI (rs7975232) gene polymorphisms and the risk of rickets among Asians, most of
      whom were from China. B allele/BB genotype was associated with the susceptibility
      of rickets (p=0.017 and 0.044, respectively), and bb genotype was associated with
      lower risk of rickets (p=0.033). F allele/FF genotype was associated with the
      susceptibility of rickets (p<10(-4)), and ff genotype was associated with lower
      risk of rickets (p<10(-4)). AA genotype was associated with the onset of rickets
      (p=0.044). No significant association was observed between TaqI polymorphism the
      risk of rickets. A allele/aa genotype was not associated with the risk of
      rickets. No evidence of publication bias was observed. CONCLUSIONS: B allele/BB
      genotype at the BsmI site, F allele/FF genotype at the FokI site and AA genotype
      at the ApaI site may be risk factors for the onset of rickets among Asians; bb
      genotype at the BsmI site and ff genotype at the FokI site may be protective
      factors against the risk of rickets among Asians.

PMID- 24336387
TI  - Both-sided native valve endocarditis in an intravenous drug misuser.
AB  - Infective endocarditis (IE) is more common in left heart chambers in the general
      population. Right-sided IE is increased especially in intravenous drug misusers.
      However, involvement of both right and left heart chambers is extremely rare in
      these patients. In this study, we present the case of a 26-year-old male
      intravenous drug misuser, hospitalised with Staphylococcal tricuspid valve IE
      complicated with pulmonary septic embolism. After 10 days, an echocardiogram
      revealed vegetation on the mitral valve in addition to unchanged tricuspid valve
      vegetation. IE can be a rapidly progressive disease despite the medical treatment
      in intravenous drug misusers. Generally, the right-sided IE is common in
      intravenous drug misusers; however, as in our case, it may involve left heart
      chambers as well. Therefore, in the right-sided IE cases, a serial
      echocardiographic examination of both heart chambers is strictly recommended. 

PMID- 24336388
TI  - A rare mimic of contained cardiac rupture: a diagnostic and therapeutic dilemma
      at a crucial time.

PMID- 24336390
TI  - Photoreleasable thiol chemistry for facile and efficient bioconjugation.
AB  - A facile methodology for light-triggered release of thiols under mild conditions
      is presented, which can be utilized for in situ bioconjugation with protein and
      quantum dot nanoparticles (QDs) efficiently. 

PMID- 24336389
TI  - Nitric oxide induces cotyledon senescence involving co-operation of the NES1/MAD1
      and EIN2-associated ORE1 signalling pathways in Arabidopsis.
AB  - After germination, cotyledons undertake the major role in supplying nutrients to
      the pre-photoautorophy angiosperm seedlings until they senesce. Like other
      senescence processes, cotyledon senescence is a programmed degenerative process.
      Nitric oxide can induce premature cotyledon senescence in Arabidopsis thaliana,
      yet the underlying mechanism remains elusive. A screen for genetic mutants
      identified the nes1 mutant, in which cotyledon senescence was accelerated by
      nitric oxide. Map-based cloning revealed that NES1 is allelic to a previously
      reported mitotic checkpoint family gene, MAD1. The nes1/mad1 mutants were
      restored to the wild type, in response to nitric oxide, by transforming them with
      pNES1::NES1. Ectopic expression of NES1 in the wild type delayed nitric oxide
      mediated cotyledon senescence, confirming the repressive role of NES1. Moreover,
      two positive regulators of leaf senescence, the ethylene signalling component
      EIN2 and the transcription factor ORE1/AtNAC2/ANAC092, were found to function
      during nitric oxide-induced senescence in cotyledons. The block of ORE1 function
      delayed senescence and ectopic expression induced the process, revealing the
      positive role of ORE1. EIN2 was required to induce ORE1. Furthermore, the genetic
      interaction analysis between NES1 and ORE1 showed that the ore1 loss-of-function
      mutants were epistatic to nes1, suggesting the dominant role of ORE1 and the
      antagonistic role of NES1 during nitric oxide-induced cotyledon senescence in
      Arabidopsis. 

PMID- 24336391
TI  - Tactile stimulation can suppress visual perception.
AB  - An input (e.g., airplane takeoff sound) to a sensory modality can suppress the
      percept of another input (e.g., talking voices of neighbors) of the same
      modality. This perceptual suppression effect is evidence that neural responses to
      different inputs closely interact with each other in the brain. While recent
      studies suggest that close interactions also occur across sensory modalities,
      crossmodal perceptual suppression effect has not yet been reported. Here, we
      demonstrate that tactile stimulation can suppress the percept of visual stimuli:
      Visual orientation discrimination performance was degraded when a tactile
      vibration was applied to the observer's index finger of hands. We also
      demonstrated that this tactile suppression effect on visual perception occurred
      primarily when the tactile and visual information were spatially and temporally
      consistent. The current findings would indicate that neural signals could closely
      and directly interact with each other, sufficient to induce the perceptual
      suppression effect, even across sensory modalities. 

PMID- 24336392
TI  - Planning for closure: the role of special administrators in reducing NHS hospital
      services in England.

PMID- 24336393
TI  - A smart hybrid system of Au nanoparticle immobilized PDMAEMA brushes for
      thermally adjustable catalysis.
AB  - A smart hybrid system was prepared by introducing the temperature responsive
      PDMAEMA brushes and Au NPs into silica NPs through self-initiated photografting
      and photopolymerization (SIPGP) and reduction of HAuCl4. The obtained
      SiO2@PDMAEMA-Au hybrid system was investigated to have a thermally adjustable
      catalytic activity for the reduction of 4-nitrophenol. 

PMID- 24336394
TI  - Resonance energy transfer-based fluorescent probes for Hg2+, Cu2+ and Fe2+/Fe3+
      ions.
AB  - Resonance energy transfer (RET) between donor-acceptor architecture is an
      important physical mechanism which is used enormously for the development of
      fluorescent probes. The unique advantage of RET is its ability to transfer energy
      non-radiatively between molecules over biologically relevant distances. The
      distance dependency of RET makes this approach suitable for bioanalysis such as
      distances between biomolecules and molecular level interactions, both in vitro
      and in vivo. In addition, RET is a proficient approach for the development of
      fluorescent probes with ratiometric measurements. In the recent years, resonance
      energy transfer has been extensively applied for the design of fluorescent
      sensors for different types of analytes such as metal ions, anions, reactive
      oxygen species and molecules of biological interest. In this review, our aim is
      to highlight the applications of resonance energy transfer mechanisms, i.e.
      Forster or fluorescence resonance energy transfer (FRET) and through-bond energy
      transfer (TBET) for the development of fluorescent probes, mainly for Hg(2+),
      Cu(2+) and Fe(2+)/Fe(3+) ions. 

PMID- 24336395
TI  - Counterion effects in the catalytic stereoselective synthesis of 2,3'
      pyrrolidinyl spirooxindoles.
AB  - A Lewis acid-catalyzed stereoselective [3+2] annulation of crotylsilanes with
      iminooxindoles is reported to access 2,3'-pyrrolidinyl spirooxindoles with four
      stereocenters. The addition of NaBArF significantly enhances reactivity, allowing
      either metal salts or acidic clay to be effective catalysts for the
      stereoselective reaction. 

PMID- 24336396
TI  - Racial/Ethnic differences among smokers: revisited and expanded to help seekers.
AB  - INTRODUCTION: Most research on racial/ethnic differences among smokers is
      outdated and does not focus on help seekers. The purpose of this study was to
      revisit racial/ethnic differences in variables related to cessation in a sample
      of smokers enrolled in a randomized trial. METHODS: Adult smokers (N = 417; n =
      126 White; n = 123 Hispanic; n = 168 Black) completed measures of demographics,
      smoking history, alcohol use, depressive symptoms, and readiness to quit.
      RESULTS: We found significant differences in these factors across groups. Blacks
      were more likely to be older, less educated, single, low income, smoke menthol
      cigarettes, and report greater nicotine dependence. Hispanics were younger,
      reported fewer years smoking and cigarettes per day, lower nicotine dependence,
      preferred mentholated cigarettes, and reported greater alcohol use intensity.
      After controlling for demographics and smoking history, Blacks reported greater
      depressive symptoms and lower readiness to quit compared with Whites and
      Hispanics. CONCLUSIONS: Help-seeking Blacks may exhibit more risk factors for
      difficulty quitting compared with other groups. Hispanics may have some
      protective factors, such as lower dependence, but require attention to alcohol
      use and menthol smoking. Identifying preintervention racial/ethnic differences in
      characteristics related to cessation is important for developing evidence-based
      and culturally specific interventions and for reducing tobacco-related health
      disparities.

PMID- 24336397
TI  - The human body as property? Possession, control and commodification.

PMID- 24336398
TI  - Why does it matter how we regulate the use of human body parts?
AB  - Human tissue and body parts have been used in one way or another for millennia.
      They have been preserved and displayed, both in museums and public shows. Real
      human hair is used for wigs, while some artists even use human tissue in their
      works. Blood, bone marrow, whole organs and a host of other structures and human
      substances are all transplanted into living persons to treat illness. New life
      can be created from gametes through in vitro fertilisation (IVF), while the
      creation of cell lines keeps tissue alive indefinitely. These uses create
      significant challenges for the legal system in the UK. The major challenge for
      the law is to balance the competing demands of those groups who have vested
      interests in human tissue-researchers, medical practitioners, patients, families,
      the community and the police, among many others. It must provide sufficient
      control to users of tissue, but also take account of the fact that our bodies
      hold psychological importance for us while we live and, after we die, for those
      we leave behind. To some degree the law has been successful, but we still lack a
      comprehensive, coherent approach to the regulation of human tissue. Partially as
      a reaction to this lack of a comprehensive approach, some commentators have
      turned to applying the concept of property to human tissue means to achieve
      regulatory outcomes they support. 

PMID- 24336400
TI  - Prolonged preoperative fasting in elective surgical patients: why should we
      reduce it?
AB  - Despite the abundance of evidence to the contrary, 6-8 hours of total
      preoperative fasting is still considered essential by many surgeons and
      anesthesiologists, based on the strength of old concepts. Patients frequently end
      up fasting for 12 hours or more because of delays and changes in operating room
      schedules. The metabolic response to long fasting leads to intensification of the
      organic response occurring after trauma, which is mainly manifested as increased
      insulin resistance, an acute-phase response, and loss of lean body mass. In fact,
      there has not been any evidence indicating that a shorter fast of 2-3 hours,
      which includes oral clear or carbohydrate (CHO)-rich (12.5% carbohydrates, 50
      kcal/100 mL) fluids, results in an increased risk of aspiration, regurgitation,
      or related morbidity compared with the standard policy of "nil by mouth after
      midnight." In addition, preoperative treatment with CHO-rich fluids may reduce
      postoperative discomfort and, for patients undergoing major abdominal surgery,
      may decrease the duration of postoperative hospitalization. New formulas for
      preoperative oral fluids containing amino acid or protein such as glutamine or
      whey protein are also potential candidates for early preoperative treatment and
      merit further study. 

PMID- 24336401
TI  - Neonatal and pediatric peripheral parenteral nutrition: what is a safe
      osmolarity?
AB  - BACKGROUND: To reach nutrition goals, peripheral parenteral nutrition (PPN) often
      exceeds an osmolarity (Osm) of 900 mOsm/L. Evidence suggesting PPNs with Osm >
      900 mOsm/L are safe in adults. However, some pediatric data suggest the PPN Osm
      limit should be 500-700 mOsm/L, yet A.S.P.E.N. recommends a limit of 900 mOsm/L.
      MATERIALS AND METHODS: This is a retrospective cohort study from January 1, 2005,
      to December 31, 2007, to determine if PPNs with an Osm > 900 mOsm/L result in an
      increased rate of line-related events in neonatal and pediatric patients.
      Patients from birth to 21 years were included and grouped based on the final Osm
      of the PPN. The exposed group included patients with Osm > 900 mOsm/L and the
      nonexposed (NE) group Osm <= 900 mOsm/L. RESULTS: Baseline demographic data were
      similar. The mean Osm for neonatal PPNs was 856 and 944 mOsm/L for pediatric
      PPNs. For neonatal PPNs, the incidence of line-related events was 50 per 100
      patient days and 52 per 100 patient days for PPNs <= 900 and > 900 mOsm/L (RR =
      1.02, 95% CI 0.88-1.18). For pediatric PPNs, the incidence of line-related events
      was 49.5 per 100 patient days and 42.6 per 100 patient days for PPNs <= 900 and >
      900 mOsm/L (RR = 0.94, 95% CI 0.77-1.15). CONCLUSION: The final Osm of PPN did
      not effect the rate of line-related events. Prospective studies assessing the
      development of line-related events, as a result of PPN Osm, are warranted to
      confirm the data presented in this analysis.

PMID- 24336402
TI  - Free-standing kinked nanowire transistor probes for targeted intracellular
      recording in three dimensions.
AB  - Recording intracellular (IC) bioelectrical signals is central to understanding
      the fundamental behaviour of cells and cell networks in, for example, neural and
      cardiac systems. The standard tool for IC recording, the patch-clamp micropipette
      is applied widely, yet remains limited in terms of reducing the tip size, the
      ability to reuse the pipette and ion exchange with the cytoplasm. Recent efforts
      have been directed towards developing new chip-based tools, including micro-to
      nanoscale metal pillars, transistor-based kinked nanowires and nanotube devices.
      These nanoscale tools are interesting with respect to chip-based multiplexing,
      but, so far, preclude targeted recording from specific cell regions and/or
      subcellular structures. Here we overcome this limitation in a general manner by
      fabricating free-standing probes in which a kinked silicon nanowire with an
      encoded field-effect transistor detector serves as the tip end. These probes can
      be manipulated in three dimensions within a standard microscope to target
      specific cells or cell regions, and record stable full-amplitude IC action
      potentials from different targeted cells without the need to clean or change the
      tip. Simultaneous measurements from the same cell made with free-standing
      nanowire and patch-clamp probes show that the same action potential amplitude and
      temporal properties are recorded without corrections to the raw nanowire signal.
      In addition, we demonstrate real-time monitoring of changes in the action
      potential as different ion-channel blockers are applied to cells, and multiplexed
      recording from cells by independent manipulation of two free-standing nanowire
      probes. 

PMID- 24336403
TI  - Spin-resolved Andreev levels and parity crossings in hybrid superconductor
      semiconductor nanostructures.
AB  - The physics and operating principles of hybrid superconductor-semiconductor
      devices rest ultimately on the magnetic properties of their elementary subgap
      excitations, usually called Andreev levels. Here we report a direct measurement
      of the Zeeman effect on the Andreev levels of a semiconductor quantum dot with
      large electron g-factor, strongly coupled to a conventional superconductor with a
      large critical magnetic field. This material combination allows spin degeneracy
      to be lifted without destroying superconductivity. We show that a spin-split
      Andreev level crossing the Fermi energy results in a quantum phase transition to
      a spin-polarized state, which implies a change in the fermionic parity of the
      system. This crossing manifests itself as a zero-bias conductance anomaly at
      finite magnetic field with properties that resemble those expected for Majorana
      modes in a topological superconductor. Although this resemblance is understood
      without evoking topological superconductivity, the observed parity transitions
      could be regarded as precursors of Majorana modes in the long-wire limit. 

PMID- 24336404
TI  - Efficient solar water-splitting using a nanocrystalline CoO photocatalyst.
AB  - The generation of hydrogen from water using sunlight could potentially form the
      basis of a clean and renewable source of energy. Various water-splitting methods
      have been investigated previously, but the use of photocatalysts to split water
      into stoichiometric amounts of H2 and O2 (overall water splitting) without the
      use of external bias or sacrificial reagents is of particular interest because of
      its simplicity and potential low cost of operation. However, despite progress in
      the past decade, semiconductor water-splitting photocatalysts (such as (Ga1
      xZnx)(N1-xOx)) do not exhibit good activity beyond 440 nm (refs 1,2,9) and water
      splitting devices that can harvest visible light typically have a low solar-to
      hydrogen efficiency of around 0.1%. Here we show that cobalt(II) oxide (CoO)
      nanoparticles can carry out overall water splitting with a solar-to-hydrogen
      efficiency of around 5%. The photocatalysts were synthesized from non-active CoO
      micropowders using two distinct methods (femtosecond laser ablation and
      mechanical ball milling), and the CoO nanoparticles that result can decompose
      pure water under visible-light irradiation without any co-catalysts or
      sacrificial reagents. Using electrochemical impedance spectroscopy, we show that
      the high photocatalytic activity of the nanoparticles arises from a significant
      shift in the position of the band edge of the material. 

PMID- 24336405
TI  - Propagation of magnetic vortices using nanocontacts as tunable attractors.
AB  - Magnetic vortices in thin films are in-plane spiral spin configurations with a
      core in which the magnetization twists out of the film plane. Vortices result
      from the competition between atomic-scale exchange forces and long-range dipolar
      interactions. They are often the ground state of magnetic dots, and have
      applications in medicine, microwave generation and information storage. The
      compact nature of the vortex core, which is 10-20 nm wide, makes it a suitable
      probe of magnetism at the nanoscale. However, thus far the positioning of a
      vortex has been possible only in confined structures, which prevents its
      transport over large distances. Here we show that vortices can be propagated in
      an unconstrained system that comprises electrical nanocontacts (NCs). The NCs are
      used as tunable vortex attractors in a manner that resembles the propelling of
      space craft with gravitational slingshots. By passing current from the NCs to a
      ferromagnetic film, circulating magnetic fields are generated, which nucleate the
      vortex and create a potential well for it. The current becomes spin polarized in
      the film, and thereby drives the vortex into gyration through spin-transfer
      torques. The vortex can be guided from one NC to another by tuning attractive
      strengths of the NCs. We anticipate that NC networks may be used as multiterminal
      sources of vortices and spin waves (as well as heat, spin and charge flows) to
      sense the fundamental interactions between physical objects and fluxes of the
      next-generation spintronic devices.

PMID- 24336407
TI  - A small molecule two-photon fluorescent probe for intracellular sodium ions.
AB  - We report a small-molecule two-photon fluorescent probe (ANa2) for Na(+) that
      shows a strong TPEF enhancement in response to Na(+) and can be easily loaded
      into live cells and can real time monitor the fluctuation of [Na]i in live cells
      and living tissue at more than 100 MUm depth. 

PMID- 24336406
TI  - Mitochondrial DNA depletion sensitizes cancer cells to PARP inhibitors by
      translational and post-translational repression of BRCA2.
AB  - Previous studies have shown that pharmacologic inhibition of poly (ADP-ribose)
      polymerase (PARP), a nuclear protein that is crucial in signaling single-strand
      DNA breaks, is synthetically lethal to cancer cells from patients with genetic
      deficiency in the DNA repair proteins BRCA1 and BRCA2. Herein, we demonstrate
      that depletion of the mitochondrial genome (mtDNA) in breast, prostate and
      thyroid transformed cells resulted in elevated steady-state cytosolic calcium
      concentration and activation of calcineurin/PI3-kinase/AKT signaling leading to
      upregulation of miR-1245 and the ubiquitin ligase Skp2, two potent negative
      regulators of the tumor suppressor protein BRCA2, thus resulting in BRCA2 protein
      depletion, severe reduction in homologous recombination (HR) and increased
      sensitivity to the PARP inhibitor rucaparib. Treatment of mtDNA-depleted cells
      with the PI3-kinase inhibitor LY294002, the calmodulin antagonist W-7, the
      calcineurin inhibitor FK506, the calcium chelator BAPTA-AM, or suppression of AKT
      activity by AKT small-interfering RNA (siRNA) enhanced BRCA2 protein levels as
      well as HR. Decreasing the intracellular calcium levels using BAPTA, or direct
      reconstitution of BRCA2 protein levels either by recombinant expression or by
      small molecule inhibition of both Skp2 and miR-1245 restored sensitivity to
      rucaparib to wild-type levels. Furthermore, by studying prostate tissue specimens
      from prostate carcinoma patients we found a direct correlation between the
      presence of mtDNA large deletions and loss of BRCA2 protein in vivo, suggesting
      that mtDNA status may serve as a marker to predict therapeutic efficacy to PARP
      inhibitors. In summary, our results uncover a novel mechanism by which mtDNA
      depletion restrains HR, and highlight the role of mtDNA in regulating sensitivity
      to PARP inhibitors in transformed cells. 

PMID- 24336408
TI  - Electrochemical stability of non-aqueous electrolytes for sodium-ion batteries
      and their compatibility with Na(0.7)CoO2.
AB  - The present study compares the physico-chemical properties of non-aqueous liquid
      electrolytes based on NaPF6, NaClO4 and NaCF3SO3 salts in the binary mixture of
      ethylene carbonate (EC) and dimethyl carbonate (DMC). The ionic conductivity of
      the electrolytes is determined as a function of salt concentration and
      temperature. It is found that the electrolytes containing NaClO4 and NaPF6
      exhibit ionic conductivities ranging from 5 mS cm(-1) to 7 mS cm(-1) at ambient
      temperature. The electrochemical stability window of the different electrolytes
      is studied by linear sweep voltammetry (LSV) and cyclic voltammetry (CV)
      measurements with respect to a variety of working electrodes (WE) such as glassy
      carbon (GC), graphite and a carbon gas diffusion layer (GDL). Electrolytes
      containing NaPF6 and NaClO4 are found to be electrochemically stable with respect
      to GC and GDL electrodes up to 4.5 V vs. Na/Na(+), with some side reactions
      starting from around 3.0 V for the latter salt. The results further show that
      aluminium is preferred over different steels as a cathode current collector.
      Copper is stable up to a potential of 3.5 V vs. Na/Na(+). In view of practical Na
      ion battery systems, the electrolytes are electrochemically tested with Na0.7CoO2
      as a positive electrode. It is inferred that the electrolyte NaPF6-EC : DMC is
      favorable for the formation of a stable surface film and the reversibility of the
      above cathode material. 

PMID- 24336409
TI  - Silicene oxides: formation, structures and electronic properties.
AB  - Understanding the oxidation of silicon has been critical to the success of all
      types of silicon materials, which are the cornerstones of modern silicon
      technologies. For the recent experimentally obtained two-dimensional silicene,
      oxidation should also be addressed to enable the development of silicene-based
      devices. Here we focus on silicene oxides (SOs) that result from the partial or
      full oxidation of silicene in the framework of density functional theory. It is
      found that the formation of SOs greatly depends on oxidation conditions, which
      concern the oxidizing agents of oxygen and hydroxyl. The honeycomb lattice of
      silicene may be preserved, distorted or destroyed after oxidation. The charge
      state of Si in partially oxidized silicene ranges from +1 to +3, while that in
      fully oxidized silicene is +4. Metals, semimetals, semiconductors and insulators
      can all be found among the SOs, which show a wide spectrum of electronic
      structures. Our work indicates that the oxidation of silicene should be
      exquisitely controlled to obtain specific SOs with desired electronic properties.

PMID- 24336410
TI  - Intensity of vortices: from soap bubbles to hurricanes.
AB  - By using a half soap bubble heated from below, we obtain large isolated single
      vortices whose properties as well as their intensity are measured under different
      conditions. By studying the effects of rotation of the bubble on the vortex
      properties, we found that rotation favors vortices near the pole. Rotation also
      inhibits long life time vortices. The velocity and vorticity profiles of the
      vortices obtained are well described by a Gaussian vortex. Besides, the intensity
      of these vortices can be followed over long time spans revealing periods of
      intensification accompanied by trochoidal motion of the vortex center, features
      which are reminiscent of the behavior of tropical cyclones. An analysis of this
      intensification period suggests a simple relation valid for both the vortices
      observed here and for tropical cyclones. 

PMID- 24336411
TI  - A combinatorial approach to graphlet counting.
AB  - MOTIVATION: Small-induced subgraphs called graphlets are emerging as a possible
      tool for exploration of global and local structure of networks and for analysis
      of roles of individual nodes. One of the obstacles to their wider use is the
      computational complexity of algorithms for their discovery and counting. RESULTS:
      We propose a new combinatorial method for counting graphlets and orbit signatures
      of network nodes. The algorithm builds a system of equations that connect counts
      of orbits from graphlets with up to five nodes, which allows to compute all orbit
      counts by enumerating just a single one. This reduces its practical time
      complexity in sparse graphs by an order of magnitude as compared with the
      existing pure enumeration-based algorithms. AVAILABILITY AND IMPLEMENTATION:
      Source code is available freely at http://www.biolab.si/supp/orca/orca.html.

PMID- 24336412
TI  - slaMEM: efficient retrieval of maximal exact matches using a sampled LCP array.
AB  - MOTIVATION: Maximal exact matches, or just MEMs, are a powerful tool in the
      context of multiple sequence alignment and approximate string matching. The most
      efficient algorithms to collect them are based on compressed indexes that rely on
      longest common prefix array-centered data structures. However, their space
      efficient representations make use of encoding techniques that are expensive from
      a computational point of view. With the deluge of data generated by high
      throughput sequencing, new approaches need to be developed to deal with larger
      genomic sequences. RESULTS: In this work, we have developed a new longest common
      prefix array-sampled representation, optimized to work with the backward search
      method inherently used by the FM-Index. Unlike previous implementations that
      sacrifice running time to have smaller space, ours lead to both a fast and a
      space-efficient approach. This implementation was used by the new software
      slaMEM, developed to efficiently retrieve MEMs. The results show that the new
      algorithm is competitive against existing state-of-the-art approaches.
      AVAILABILITY AND IMPLEMENTATION: The software is implemented in C and is
      operating system independent. The source code is freely available for download at
      http://github.com/fjdf/slaMEM/ under the GPLv3 license.

PMID- 24336413
TI  - HAMMER: automated operation of mass frontier to construct in silico mass spectral
      fragmentation libraries.
AB  - SUMMARY: Experimental MS(n) mass spectral libraries currently do not adequately
      cover chemical space. This limits the robust annotation of metabolites in
      metabolomics studies of complex biological samples. In silico fragmentation
      libraries would improve the identification of compounds from experimental
      multistage fragmentation data when experimental reference data are unavailable.
      Here, we present a freely available software package to automatically control
      Mass Frontier software to construct in silico mass spectral libraries and to
      perform spectral matching. Based on two case studies, we have demonstrated that
      high-throughput automation of Mass Frontier allows researchers to generate in
      silico mass spectral libraries in an automated and high-throughput fashion with
      little or no human intervention required. AVAILABILITY AND IMPLEMENTATION:
      Documentation, examples, results and source code are available at
      http://www.biosciences-labs.bham.ac.uk/viant/hammer/.

PMID- 24336414
TI  - BEAMS: backbone extraction and merge strategy for the global many-to-many
      alignment of multiple PPI networks.
AB  - MOTIVATION: Global many-to-many alignment of biological networks has been a
      central problem in comparative biological network studies. Given a set of
      biological interaction networks, the informal goal is to group together related
      nodes. For the case of protein-protein interaction networks, such groups are
      expected to form clusters of functionally orthologous proteins. Construction of
      such clusters for networks from different species may prove useful in determining
      evolutionary relationships, in predicting the functions of proteins with unknown
      functions and in verifying those with estimated functions. RESULTS: A central
      informal objective in constructing clusters of orthologous proteins is to
      guarantee that each cluster is composed of members with high homological
      similarity, usually determined via sequence similarities, and that the
      interactions of the proteins involved in the same cluster are conserved across
      the input networks. We provide a formal definition of the global many-to-many
      alignment of multiple protein-protein interaction networks that captures this
      informal objective. We show the computational intractability of the suggested
      definition. We provide a heuristic method based on backbone extraction and merge
      strategy (BEAMS) for the problem. We finally show, through experiments based on
      biological significance tests, that the proposed BEAMS algorithm performs better
      than the state-of-the-art approaches. Furthermore, the computational burden of
      the BEAMS algorithm in terms of execution speed and memory requirements is more
      reasonable than the competing algorithms. AVAILABILITY AND IMPLEMENTATION:
      Supplementary material including code implementations in LEDA C++, experimental
      data and the results are available at
      http://webprs.khas.edu.tr/~cesim/BEAMS.tar.gz.

PMID- 24336415
TI  - Time-place learning and memory persist in mice lacking functional Per1 and Per2
      clock genes.
AB  - With time-place learning, animals link a stimulus with the location and the time
      of day. This ability may optimize resource localization and predator avoidance in
      daily changing environments. Time-place learning is a suitable task to study the
      interaction of the circadian system and memory. Previously, we showed that time
      place learning in mice depends on the circadian system and Cry1 and/or Cry2 clock
      genes. We questioned whether time-place learning is Cry specific or also depends
      on other core molecular clock genes. Here, we show that Per1/Per2 double mutant
      mice, despite their arrhythmic phenotype, acquire time-place learning similar to
      wild-type mice. As well as an established role in circadian rhythms, Per genes
      have also been implicated in the formation and storage of memory. We found no
      deficiencies in short-term spatial working memory in Per mutant mice compared to
      wild-type mice. Moreover, both Per mutant and wild-type mice showed similar long
      term memory for contextual features of a paradigm (a mild foot shock), measured
      in trained mice after a 2-month nontesting interval. In contrast, time-place
      associations were lost in both wild-type and mutant mice after these 2 months,
      suggesting a lack of maintained long-term memory storage for this type of
      information. Taken together, Cry-dependent time-place learning does not require
      Per genes, and Per mutant mice showed no PER-specific short-term or long-term
      memory deficiencies. These results limit the functional role of Per clock genes
      in the circadian regulation of time-place learning and memory. 

PMID- 24336416
TI  - Strong (type 0) phase resetting of activity-rest rhythm in fruit flies,
      Drosophila melanogaster, at low temperature.
AB  - Amplitude modulation in limit cycle models of circadian clocks has been
      previously formulated to explain the phenomenon of temperature compensation.
      These models propose that invariance of clock period (tau) with changing
      temperature is a result of the system traversing small or large limit cycles such
      that despite a decrease or an increase in the linear velocity of the clock owing
      to slowing down or speeding up of the underlying biochemical reactions,
      respectively, the angular velocity and, thus, the clock period remain constant.
      In addition, these models predict that phase resetting behavior of circadian
      clocks described by limit cycles of different amplitudes at low or high
      temperatures will be drastically different. More specifically, this class of
      models predicts that at low temperatures, circadian clocks will respond to
      perturbations by eliciting larger phase shifts by virtue of their smaller
      amplitude and vice versa. Here, we present the results of our tests of this
      prediction: We examined the nature of photic phase response curves (PRCs) and
      phase transition curves (PTCs) for the circadian clocks of 4 wild-type fruit fly
      Drosophila melanogaster populations at 3 different ambient temperatures (18, 25,
      and 29  degrees C). Interestingly, we observed that at the low temperature of 18 
      degrees C, fly clocks respond to light perturbations more strongly, eliciting
      strong (type 0) PRCs and PTCs, while at moderate (25  degrees C) and high (29 
      degrees C) temperatures the same stimuli evoke weak (type 1) responses. This
      pattern of strong and weak phase resetting at low and high temperatures,
      respectively, renders support for the limit cycle amplitude modulation model for
      temperature compensation of circadian clocks. 

PMID- 24336417
TI  - The bird circadian clock: insights from a computational model.
AB  - The circadian timekeeping system appears more complex in birds than in mammals.
      In mammals, the main pacemaker is centralized in the suprachiasmatic nuclei,
      whereas in birds, the pacemaker involves the interplay between the pineal and
      hypothalamic oscillators. In order to investigate the consequence of this complex
      mechanism, we propose here a mathematical model for the bird circadian clock. The
      model is based on the internal resonance between the pineal and hypothalamic
      oscillators, each described by Goodwin-like equations. We show that, consistently
      with experimental observations, self-sustained oscillations can be generated by
      mutual inhibitory coupling of the 2 clocks, even if individual oscillators
      present damped oscillations. We study the effect of constant and periodic
      administrations of melatonin, which, in intact birds, acts as the coupling
      variable between the pineal and the hypothalamus, and compare the prediction of
      the model with the experiments performed in pinealectomized birds. We also assess
      the entrainment properties when the system is subject to light-dark cycles.
      Analyses of the entrainment range, resynchronization time after jet lag, and
      entrainment phase with respect to the photoperiod lead us to formulate hypotheses
      about the physiological advantage of the particular architecture of the avian
      circadian clock. Although minimal, our model opens promising perspectives in
      modeling and understanding the bird circadian clock. 

PMID- 24336418
TI  - Body temperature predicts the direction of internal desynchronization in humans
      isolated from time cues.
AB  - This publication presents a new analysis of experiments that were carried out in
      human subjects in isolation from time cues, under supervision of Jurgen Aschoff
      and Rutger Wever at the Max Planck Institute for Behavioural Physiology (Erling
      Andechs, Germany, 1964-1974). Mean rectal temperatures (tb) were compared between
      subjects who showed internal desynchronization (ID) and internal synchronization
      (IS) of the endogenous rhythms of sleep-wakefulness and of body temperature. The
      results showed that tb was reduced in long ID (circadian sleep-wake cycle length
      [tau(SW)] > 27 h) and increased in short ID (tau(SW) < 22 h) relative to IS. In
      subjects with both ID and IS sections in the complete record, these differences
      were also found when comparing only the IS sections: Low tb during IS predicts
      the later occurrence of long ID, and high tb predicts the incidence of short ID.
      While this association is associated with sex differences in tb, it also occurs
      within each sex. To the extent that the variation in tb reflects the variation in
      heat production (metabolic rate), the results are consistent with the proposition
      that the spontaneous frequency of the human sleep-wake oscillator is associated
      with the metabolic rate, as suggested on the basis of the proportionality of meal
      frequency and sleep-wake frequency. The finding thus has implications for our
      views on spontaneous sleep timing.

PMID- 24336419
TI  - Temporal dynamics of ocular indicators of sleepiness across sleep restriction.
AB  - The current study characterized the temporal dynamics of ocular indicators of
      sleepiness during extended sleep restriction. Ten male participants (mean age +/-
      SD = 23.3 +/- 1.6 years) underwent 40 h of continuous wakefulness under constant
      routine (CR) conditions; they completed the Karolinska Sleepiness Scale (KSS) and
      a 10-min auditory psychomotor vigilance task (aPVT) hourly. Waking
      electroencephalography (EEG) and ocular measures were recorded continuously
      throughout the CR. Infrared-reflectance oculography was used to collect the
      ocular measures positive and negative amplitude-velocity ratio, mean blink
      duration, the percentage of eye closure, and a composite score of sleepiness
      levels (Johns Drowsiness Scale). All ocular measures, except blink duration,
      displayed homeostatic and circadian properties. Only circadian effects were
      detected in blink duration. Significant, phase-locked cross-correlations (p <
      0.05) were detected between ocular measures and aPVT reaction time (RT), aPVT
      lapses, KSS, and EEG delta-theta (0.5-5.5 Hz), theta-alpha (5.0-9.0 Hz), and beta
      (13.0-20.0 Hz) activity. Receiver operating characteristic curve analysis
      demonstrated reasonable sensitivity and specificity of ocular measures in
      correctly classifying aPVT lapses above individual baseline thresholds (initial
      16 h of wakefulness). Under conditions of sleep restriction, ocular indicators of
      sleepiness paralleled performance impairment and self-rated sleepiness levels,
      and demonstrated their potential to detect sleepiness-related attentional lapses.
      These findings, if reproduced in a larger sample, will have implications for the
      use of ocular-based sleepiness-warning systems in operational settings. 

PMID- 24336420
TI  - Sex of college students moderates associations among bedtime, time in bed, and
      circadian phase angle.
AB  - Sex differences in circadian rhythms have been reported with some conflicting
      results. The timing of sleep and length of time in bed have not been considered,
      however, in previous such studies. The current study has 3 major aims: (1)
      replicate previous studies in a large sample of young adults for sex differences
      in sleep patterns and dim light melatonin onset (DLMO) phase; (2) in a subsample
      constrained by matching across sex for bedtime and time in bed, confirm sex
      differences in DLMO and phase angle of DLMO to bedtime; (3) explore sex
      differences in the influence of sleep timing and length of time in bed on phase
      angle. A total of 356 first-year Brown University students (207 women) aged 17.7
      to 21.4 years (mean = 18.8 years, SD = 0.4 years) were included in these
      analyses. Wake time was the only sleep variable that showed a sex difference.
      DLMO phase was earlier in women than men and phase angle wider in women than men.
      Shorter time in bed was associated with wider phase angle in women and men. In
      men, however, a 3-way interaction indicated that phase angles were influenced by
      both bedtime and time in bed; a complex interaction was not found for women.
      These analyses in a large sample of young adults on self-selected schedules
      confirm a sex difference in wake time, circadian phase, and the association
      between circadian phase and reported bedtime. A complex interaction with length
      of time in bed occurred for men but not women. We propose that these sex
      differences likely indicate fundamental differences in the biology of the sleep
      and circadian timing systems as well as in behavioral choices. 

PMID- 24336421
TI  - Fluorescent immunosensor based on CuS nanoparticles for sensitive detection of
      cancer biomarker.
AB  - A novel fluorescent immunosensor was developed based on the use of CuS
      nanoparticles (CuS NPs) as labels for the highly sensitive detection of human
      prostate cancer biomarker prostate specific antigen (PSA). In the presence of CuS
      NPs, the non-fluorescent substrate o-phenylenediamine could be oxidized into the
      stable fluorescent product 2,3-diamiophenazine at physiological pH. Throughout
      the reaction, no other oxidizing agents (e.g. hydrogen peroxide) were needed. The
      relatively mild oxidation conditions made the immunoassay robust, reliable and
      facile. The proposed immunoassay exhibited high sensitivity and specificity for
      the detection of PSA. A linear relationship between the fluorescent signals and
      the concentration of PSA was obtained in the range of 0.5 pg mL(-1) to 50 ng mL(
      1), with a detection limit of 0.1 pg mL(-1) (S/N = 3). The proposed fluorescent
      immunoassay can be used as a promising platform for the detection of a variety of
      other biomarkers. 

PMID- 24336423
TI  - Circumspectives: viewing a topic from multiple perspectives.

PMID- 24336422
TI  - Transcriptome profiling of the newborn mouse lung response to acute ozone
      exposure.
AB  - Ozone pollution is associated with adverse effects on respiratory health in
      adults and children but its effects on the neonatal lung remain unknown. This
      study was carried out to define the effect of acute ozone exposure on the
      neonatal lung and to profile the transcriptome response. Newborn mice were
      exposed to ozone or filtered air for 3h. Total RNA was isolated from lung tissues
      at 6 and 24h after exposure and was subjected to microarray gene expression
      analysis. Compared to filtered air-exposed littermates, ozone-exposed newborn
      mice developed a small but significant neutrophilic airway response associated
      with increased CXCL1 and CXCL5 expression in the lung. Transcriptome analysis
      indicated that 455 genes were down-regulated and 166 genes were up-regulated by
      at least 1.5-fold at 6h post-ozone exposure (t-test, p < .05). At 24h, 543 genes
      were down-regulated and 323 genes were up-regulated in the lungs of ozone
      exposed, compared to filtered air-exposed, newborn mice (t-test, p < .05). After
      controlling for false discovery rate, 50 genes were identified as significantly
      down-regulated and only a few (RORC, GRP, VREB3, and CYP2B6) were up-regulated at
      24h post-ozone exposure (q < .05). Gene ontology enrichment analysis revealed
      that cell cycle-associated functions including cell division/proliferation were
      the most impacted pathways, which were negatively regulated by ozone exposure, an
      adverse effect that was associated with reduced bromo-deoxyuridine incorporation.
      These results demonstrate that acute ozone exposure alters cell proliferation in
      the developing neonatal lung through a global suppression of cell cycle function.

PMID- 24336425
TI  - Use of formal advance care planning documents: a national survey of UK Paediatric
      Intensive Care Units.
AB  - OBJECTIVE: Advance Care Planning (ACP) is nationally a core element of adult and
      paediatric palliative care strategies. It is defined as a process of discussion
      between an individual, their care providers and those close to them, about future
      care. Formal procedures and processes can help with some of the most difficult
      elements of communication related to ACP. The majority of children who die do so
      in a Paediatric Intensive Care Unit (PICU). This survey aimed to identify and
      compare paediatric ACP documents that are in use within UK hospitals with a PICU.
      DESIGN: Email survey of lead clinicians from UK PICUs (n=28). RESULTS: 24 (86%)
      questionnaires were returned. 14 (58%) responded that formal ACP documents were
      currently in use within their hospital trust. Of the remainder, 2 (8%) detailed
      plans to launch local ACP documents in the near future, 1 (4%) had a 'Children
      and Young Persons Deterioration Management (CAYPDM) Document' and 3 (12%) listed
      rapid discharge and extubation pathways. 6 (25%) provided details of the document
      in use. They varied widely in terms of their presentation, content and intended
      use with some having been developed locally and others having been adopted across
      regions. CONCLUSIONS: There is variation around the UK in the existence of formal
      ACP documents for paediatric patients with palliative care needs, as well as
      variation in the type of document that is used. Consideration of a national
      policy should be informed by further review and evaluation of these documents, as
      well as current practice in ACP.

PMID- 24336424
TI  - Is ftsH the key to plastid longevity in sacoglossan slugs?
AB  - Plastids sequestered by sacoglossan sea slugs have long been a puzzle. Some
      sacoglossans feed on siphonaceous algae and can retain the plastids in the
      cytosol of their digestive gland cells. There, the stolen plastids (kleptoplasts)
      can remain photosynthetically active in some cases for months. Kleptoplast
      longevity itself challenges current paradigms concerning photosystem turnover,
      because kleptoplast photosystems remain active in the absence of nuclear algal
      genes. In higher plants, nuclear genes are essential for plastid maintenance, in
      particular, for the constant repair of the D1 protein of photosystem II. Lateral
      gene transfer was long suspected to underpin slug kleptoplast longevity, but
      recent transcriptomic and genomic analyses show that no algal nuclear genes are
      expressed from the slug nucleus. Kleptoplast genomes themselves, however, appear
      expressed in the sequestered state. Here we present sequence data for the
      chloroplast genome of Acetabularia acetabulum, the food source of the sacoglossan
      Elysia timida, which can maintain Acetabularia kleptoplasts in an active state
      for months. The data reveal what might be the key to sacoglossan kleptoplast
      longevity: plastids that remain photosynthetically active within slugs for
      periods of months share the property of encoding ftsH, a D1 quality control
      protease that is essential for photosystem II repair. In land plants, ftsH is
      always nuclear encoded, it was transferred to the nucleus from the plastid genome
      when Charophyta and Embryophyta split. A replenishable supply of ftsH could, in
      principle, rescue kleptoplasts from D1 photodamage, thereby influencing plastid
      longevity in sacoglossan slugs.

PMID- 24336426
TI  - Characterization of novel plasmid-mediated beta-lactamases (SHV-167 and ACT-16)
      associated with New Delhi metallo-beta-lactamase-1 harbouring isolates from
      neonates in India.
AB  - Neonatal sepsis due to carbapenem-resistant bacteria is difficult to treat due to
      limited therapeutic options. The detection of the new carbapenemase New Delhi
      metallo-beta-lactamase-1 (NDM-1) from neonates has further complicated the
      situation (Roy et al., 2011a). The potent metallo-beta-lactamase NDM-1
      efficiently hydrolyses all classes of beta-lactam antibiotics (penicillins,
      cephalosporins and carbapenems) and is also associated with multiple determinants
      that enable the bacteria to become resistant to other antibiotic classes
      (Nordmann et al., 2011). In the presence of NDM-1 other beta-lactamases may go
      unobserved because of the spectrum of activity of NDM-1 against all beta-lactam
      antibiotics. Thus, under the canopy of the NDM-1 these beta-lactamases also get
      the opportunity to spread. This communication reports association of two novel
      beta-lactamases, SHV-type beta-lactamase (SHV-167) and AmpC-type beta-lactamase
      (ACT-16), in two NDM-1-carrying Enterobacteriaceae isolated from the blood of two
      septicaemic neonates admitted to a neonatal intensive care unit. 

PMID- 24336427
TI  - Life satisfaction and frequency of doctor visits.
AB  - OBJECTIVE: Identifying positive psychological factors that reduce health care use
      may lead to innovative efforts that help build a more sustainable and high
      quality health care system. Prospective studies indicate that life satisfaction
      is associated with good health behaviors, enhanced health, and longer life, but
      little information about the association between life satisfaction and health
      care use is available. We tested whether higher life satisfaction was
      prospectively associated with fewer doctor visits. We also examined potential
      interactions between life satisfaction and health behaviors. METHODS:
      Participants were 6379 adults from the Health and Retirement Study, a prospective
      and nationally representative panel study of American adults older than 50 years.
      Participants were tracked for 4 years. We analyzed the data using a generalized
      linear model with a gamma distribution and log link. RESULTS: Higher life
      satisfaction was associated with fewer doctor visits. On a 6-point life
      satisfaction scale, each unit increase in life satisfaction was associated with
      an 11% decrease in doctor visits--after adjusting for sociodemographic factors
      (relative risk = 0.89, 95% confidence interval = 0.86-0.93). The most satisfied
      respondents (n = 1121; 17.58%) made 44% fewer doctor visits than did the least
      satisfied (n = 182; 2.85%). The association between higher life satisfaction and
      reduced doctor visits remained even after adjusting for baseline health and a
      wide range of sociodemographic, psychosocial, and health-related covariates
      (relative risk = 0.96, 95% confidence interval = 0.93-0.99). CONCLUSIONS: Higher
      life satisfaction is associated with fewer doctor visits, which may have
      important implications for reducing health care costs.

PMID- 24336428
TI  - Depression and oxidative stress: results from a meta-analysis of observational
      studies.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis that quantitatively
      tests and summarizes the hypothesis that depression results in elevated oxidative
      stress and lower antioxidant levels. METHODS: We performed a meta-analysis of
      studies that reported an association between depression and oxidative stress
      and/or antioxidant status markers. PubMed and EMBASE databases were searched for
      articles published from January 1980 through December 2012. A random-effects
      model, weighted by inverse variance, was performed to pool standard deviation
      (Cohen's d) effect size estimates across studies for oxidative stress and
      antioxidant status measures, separately. RESULTS: Twenty-three studies with 4980
      participants were included in the meta-analysis. Depression was most commonly
      measured using the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition criteria. A Cohen's d effect size of 0.55 (95% confidence interval = 0.47
      0.63) was found for the association between depression and oxidative stress,
      indicating a roughly 0.55 of 1-standard-deviation increase in oxidative stress
      among individuals with depression compared with those without depression. The
      results of the studies displayed significant heterogeneity (I(2) = 80.0%, p <
      .001). A statistically significant effect was also observed for the association
      between depression and antioxidant status markers (Cohen's d = -0.24, 95%
      confidence interval = -0.33 to -0.15). CONCLUSIONS: This meta-analysis observed
      an association between depression and oxidative stress and antioxidant status
      across many different studies. Differences in measures of depression and markers
      of oxidative stress and antioxidant status markers could account for the observed
      heterogeneity. These findings suggest that well-established associations between
      depression and poor heath outcomes may be mediated by high oxidative stress.

PMID- 24336429
TI  - Psychological trauma and functional somatic syndromes: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: This meta-analysis systematically examined the association of reported
      psychological trauma and posttraumatic stress disorder (PTSD) with functional
      somatic syndromes including fibromyalgia, chronic widespread pain, chronic
      fatigue syndrome, temporomandibular disorder, and irritable bowel syndrome. Our
      goals were to determine the overall effect size of the association and to examine
      moderators of the relationship. METHODS: Literature searches identified 71
      studies with a control or comparison group and examined the association of the
      syndromes with traumatic events including abuse of a psychological, emotional,
      sexual, or physical nature sustained during childhood or adulthood, combat
      exposure, or PTSD. A random-effects model was used to estimate the pooled odds
      ratio and 95% confidence interval. Planned subgroup analyses and meta-regression
      examined potential moderators. RESULTS: Individuals who reported exposure to
      trauma were 2.7 (95% confidence interval = 2.27-3.10) times more likely to have a
      functional somatic syndrome. This association was robust against both publication
      bias and the generally low quality of the literature. The magnitude of the
      association with PTSD was significantly larger than that with sexual or physical
      abuse. The association of reported trauma with chronic fatigue syndrome was
      larger than the association with either irritable bowel syndrome or fibromyalgia.
      Studies using nonvalidated questionnaires or self-report of trauma reported
      larger associations than did those using validated questionnaires. CONCLUSIONS:
      Findings are consistent with the hypothesis that traumatic events are associated
      with an increased prevalence of functional somatic syndromes. The analyses also
      highlight limitations of the existing literature and emphasize the importance of
      prospective studies, examining the potential similarities and differences of
      these conditions, and pursuing hypothesis-driven studies of the mechanisms
      underlying the link between trauma, PTSD, and functional somatic syndromes.

PMID- 24336430
TI  - Ventricular tachyarrhythmias and mortality in patients with an implantable
      cardioverter defibrillator: impact of depression in the MIDAS cohort.
AB  - OBJECTIVE: We examined whether depression is independently associated with
      implantable cardioverter defibrillator (ICD) therapy for ventricular
      tachyarrhythmias and mortality. METHODS: A cohort of 430 consecutive patients
      with a first-time ICD (79% men; mean [standard deviation] age = 57.8 [12.1]
      years) completed the Hospital Anxiety and Depression Scale 1 day before
      implantation. During follow-up, the ICD was interrogated at 3-month intervals.
      Cox proportional hazard regression analyses were used to examine the impact of
      depression on time to first appropriate ICD therapy and all-cause mortality
      during a median follow-up period of 3.8 years. RESULTS: Of all patients, 108
      (25.1%) were depressed. Depression was not associated with time to first
      appropriate ICD therapy (unadjusted hazard ratio [HR] = 1.07, 95% confidence
      interval [CI] = 0.73-1.56). However, depression was associated with an increased
      risk for all-cause mortality (unadjusted HR = 2.18, 95% CI = 1.36-3.49).
      Depression remained independently associated with all-cause mortality (HR = 1.94,
      95% CI = 1.06-3.54, p = .031), after adjusting for demographic and clinical
      characteristics. Patients who remained depressed during the first 3 months after
      implantation were at greatest risk for dying (HR = 2.88, 95% CI = 1.29-6.45, p =
      .010). CONCLUSIONS: The current study showed that depression at the time of
      implant is not associated with time to first appropriate ICD therapy but almost
      doubled the risk for all-cause mortality in patients with an ICD. Patients with
      persistent depression during the first 3 months after implantation face the
      greatest risk of dying. Current evidence indicates that multifactorial
      interventions are likely to be the most successful in terms of reducing distress.
      Whether this translates into enhanced survival has yet to be determined.

PMID- 24336431
TI  - Pathophysiology of childhood polycystic kidney diseases: new insights into
      disease-specific therapy.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive
      polycystic kidney disease (ARPKD) are significant causes of morbidity and
      mortality in children and young adults. ADPKD, with an incidence of 1:400 to
      1:1,000, affects more than 13 million individuals worldwide and is a major cause
      of end-stage renal disease in adults. However, symptomatic disease is
      increasingly recognized in children. ARPKD is a dual-organ hepatorenal disease
      with an incidence of 1:20,000 to 1:40,000 and a heterozygote carrier rate of 1 in
      70. Currently, no clinically significant disease-specific therapy exists for
      ADPKD or ARPKD. The genetic basis of both ADPKD and ARPKD have been identified,
      and delineation of the basic molecular and cellular pathophysiology has led to
      the discovery that abnormal ADPKD and ARPKD gene products interact to create
      "polycystin complexes" located at multiple sites within affected cells. The
      extracellular matrix and vessels produce a variety of soluble factors that affect
      the biology of adjacent cells in many dynamic ways. This review will focus on the
      molecular and cellular bases of the abnormal cystic phenotype and discuss the
      clinical translation of such basic data into new therapies that promise to alter
      the natural history of disease for children with genetic PKDs. 

PMID- 24336432
TI  - What brakes the preterm brain? An arresting story.
AB  - Children surviving premature birth have a high risk of cognitive and learning
      disabilities and attention deficit. In turn, adverse outcomes are associated with
      persistent reductions in cerebral growth on magnetic resonance imaging (MRI). It
      is striking that modern care has been associated with a dramatic reduction in the
      risk of cystic white matter damage, but modest improvements in terms of
      neurodevelopmental impairment. This review will explore the hypothesis that the
      disability is primarily associated with impaired neural connectivity rather than
      cell death alone. Very preterm infants exhibit reduced thalamocortical
      connectivity and cortical neuroplasticity compared with term-born controls. In
      preterm fetal sheep, moderate cerebral ischemia with no neuronal loss, but
      significant diffuse failure of maturation of cortical pyramidal neurons, was
      associated with impaired dendritic growth and synapse formation, consistent with
      altered connectivity. These changes were associated with delayed decline in
      cortical fractional anisotropy (FA) on MRI. Supporting these preclinical
      findings, preterm human survivors showed similar enduring impairment of
      microstructural development of the cerebral cortex defined by FA, consistent with
      delayed formation of neuronal processes. These findings offer the promise that
      better understanding of impairment of neural connectivity may allow us to promote
      normal development and growth of the cortex after preterm birth. 

PMID- 24336433
TI  - Astrocytes and microglia in acute cerebral injury underlying cerebral palsy
      associated with preterm birth.
AB  - Cerebral palsy is one of the most devastating consequences of brain injury around
      the time of birth, and nearly a third of cases are now associated with premature
      birth. Compared with term babies, preterm babies have an increased incidence of
      complications that may increase the risk of disability, such as intraventricular
      hemorrhage, periventricular leukomalacia, sepsis, and necrotizing enterocolitis.
      The response to injury is highly dependent on brain maturity, and although
      cellular vulnerability is well documented, there is now evidence that
      premyelinating axons are also particularly sensitive to ischemic injury. In this
      review, we will explore recent evidence highlighting a central role for glia in
      mediating increased risk of disability in premature infants, including excessive
      activation of microglia and opening of astrocytic gap junction hemichannels in
      spreading injury after brain ischemia, in part likely involving release of
      adenosine triphosphate (ATP) and overactivation of purinergic receptors,
      particularly in white matter. We propose the hypothesis that inflammation-induced
      opening of connexin hemichannels is a key regulating event that initiates a
      vicious circle of excessive ATP release, which in turn propagates activation of
      purinergic receptors on microglia and astrocytes. This suggests that developing
      effective neuroprotective strategies for preterm infants requires a detailed
      understanding of glial responses. 

PMID- 24336434
TI  - An improved G-quadruplex DNAzyme for dual-functional electrochemical biosensing
      of adenosines and hydrogen peroxide from cancer cells.
AB  - A dual-functional electrochemical biosensor for adenosines and hydrogen peroxide
      from cancer cells was developed based on a traditional switchable electrochemical
      sensing format and ATP improved G-quadruplex DNAzyme as a biolabel. 

PMID- 24336436
TI  - Could there be an alternative explanation for cardiomyopathy in an infant
      following fosphenytoin overdose?

PMID- 24336435
TI  - Mechanosensing of DNA bending in a single specific protein-DNA complex.
AB  - Many crucial biological processes are regulated by mechanical stimuli. Here, we
      report new findings that pico-Newton forces can drastically affect the stability
      of the site-specific DNA binding of a single transcription factor, the E. coli
      integration host factor (IHF), by stretching a short ~150 nm DNA containing a
      single IHF binding site. Dynamic binding and unbinding of single IHF were
      recorded and analyzed for the force-dependent stability of the IHF-DNA complex.
      Our results demonstrate that the IHF-DNA interaction is fine tuned by force in
      different salt concentration and temperature over physiological ranges,
      indicating that, besides other physiological factors, force may play equally
      important role in transcription regulation. These findings have broad
      implications with regard to general mechanosensitivity of site-specific DNA
      bending proteins. 

PMID- 24336437
TI  - Detergent pod ingestions in young children: a case series.

PMID- 24336438
TI  - Demonstrating and assessing metered-dose inhaler-spacer technique: pediatric care
      providers' self-reported practices and perceived barriers.
AB  - The National Asthma Education and Prevention Program recommends that providers
      demonstrate and assess metered-dose inhaler-spacer (MDI-S) technique at each
      medical visit. To examine practice behaviors and perceived barriers to
      demonstrating and assessing MDI-S technique, we surveyed pediatric providers (n =
      114) at an inner-city academic medical center. While 82% of providers
      demonstrated MDI-S technique, only 5% of providers demonstrate the technique at
      every visit. Although 67% of providers assessed MDI-S technique, only 13% assess
      the technique at every visit. None of the providers used MDI-S checklist for
      assessment. Attendings were more likely than residents to demonstrate with
      illustrations (24% vs 6%, P = .01) and when patient's asthma was not well
      controlled (68% vs 47%, P = .05). Provider-identified barriers included limited
      access to MDI-S device, lack of time, and inadequate knowledge. Suggestions to
      address barriers include in-service training, device access, and nurse/health
      educators to alleviate the time constraints. Clinic modifications and education
      are needed. 

PMID- 24336439
TI  - Systemic loxoscelism in a nonendemic area: a diagnostic challenge for the
      unsuspecting physician.

PMID- 24336440
TI  - The curious case of hypoxemia.

PMID- 24336441
TI  - Non-collinear interaction of photons with orbital angular momentum.
AB  - We study the nonlinear interaction between two non-collinear light beams that
      carry orbital angular momentum (OAM). More specifically, two incident beams
      interact at an angle in a medium with a second order nonlinearity and thus
      generate a third, non-collinear beam at the second harmonic frequency that
      experiences a reduced conversion efficiency in comparison to that expected based
      on conventional phase-matching theory. This reduction scales with the input beam
      OAM and, differently from previous spiral bandwidth calculations, is due to a
      geometric effect whereby the input OAM is projected along the non-collinear
      interaction direction. The effect is relevant even at small interaction angles
      and is further complicated at large angles by a non-conservation of the total OAM
      in the nonlinear interaction. Experiments are performed under different
      conditions and are in excellent agreement with the theory. Our results have
      implications beyond the specific case studied here of second-harmonic generation,
      in particular for parametric down-conversion of photons or in general for phase
      matched non-collinear interactions between beams with different OAM. 

PMID- 24336442
TI  - Best practices for determining resting energy expenditure in critically ill
      adults.
AB  - Indirect calorimetry (IC) is the gold standard for measuring resting energy
      expenditure (REE) in the critically ill patient. The use of predictive equations
      to develop nutrition regimens can be problematic in the critical care setting,
      because the effects that disease, injury, and stress have on REE are often varied
      and unpredictable. IC testing ensures that the specific conditions of the
      critically ill patient are taken into account, thereby preventing potential
      complications from over- and underfeeding. The clinical indications for and
      appropriate applications of IC testing are discussed. In addition, 3 case studies
      are presented that highlight the application of IC. The clinician can face
      numerous obstacles in implementing IC testing, including lack of equipment, staff
      shortages, and lack of knowledge regarding application and interpretation of the
      IC study. Recommendations for addressing these challenges are discussed. In
      addition, guidelines on ordering and interpreting the IC study are provided. Best
      practices for predictive equations in critically and acutely ill patients are
      also presented, since IC testing is not feasible in certain situations. Given the
      importance of predicting REE in the critically ill patient, it is paramount that
      more healthcare professionals incorporate IC testing into practice. A
      multidisciplinary approach is helpful in developing a well-established clinical
      practice. Nutrition support clinicians can promote optimal nutrition management
      by being well-informed and able to provide evidence-based recommendations for the
      use of IC. 

PMID- 24336443
TI  - Heavy metal in the intensive care unit: a review of current literature on trace
      element supplementation in critically ill patients.
AB  - Trace elements are essential for many physiologic processes. In recent years,
      supplementation has been studied for a variety of indications, including glycemic
      control, wound healing, antioxidant effect, and anemia. Critical illness,
      especially states such as burns, traumas, and septic shock, is associated with
      inflammatory and oxidative stress, immune dysfunction, and malnutrition. In these
      patients, enteral and parenteral nutrition or pharmaceutical supplementation is
      used to provide essential macronutrients, including trace elements. The purpose
      of this review is to describe trace element supplementation, including iron,
      copper, chromium, manganese, selenium, and zinc, and highlight their mechanism,
      pharmacology, outcome data, and adverse effects. 

PMID- 24336444
TI  - Plant nuclear photorelocation movement.
AB  - Organelle movement and positioning are essential for proper cellular function. A
      nucleus moves dynamically during cell division and differentiation and in
      response to environmental changes in animal, fungal, and plant cells. Nuclear
      movement is well-studied and the mechanisms have been mostly elucidated in animal
      and fungal cells, but not in plant cells. In prothallial cells of the fern
      Adiantum capillus-veneris and leaf cells of the flowering plant Arabidopsis
      thaliana, light induces nuclear movement and nuclei change their position
      according to wavelength, intensity, and direction of light. This nuclear
      photorelocation movement shows some common features with the photorelocation
      movement of chloroplasts, which is one of the best-characterized plant organelle
      movements. This review summarizes nuclear movement and positioning in plant
      cells, especially plant-specific nuclear photorelocation movement and discusses
      the relationship between nuclear photorelocation movement and chloroplast
      photorelocation movement. 

PMID- 24336445
TI  - Stress-induced early flowering is mediated by miR169 in Arabidopsis thaliana.
AB  - Plants interact with their environment and they often flower earlier under stress
      conditions, but how such stress-induced flowering is regulated remains poorly
      understood. Here evidence is presented that the miR169 family plays a key role in
      stress-induced flowering in plants. The microRNA (miRNA) miR169 family members
      are up-regulated in Arabidopsis, maize, and soybean under abiotic stresses.
      Overexpression of miR169d in Arabidopsis results in early flowering, and
      overexpression of the miR169d target gene, AtNF-YA2, especially a miR169d
      resistant version of AtNF-YA2, results in late flowering. The results suggest
      that the miR169 family regulates stress-induced flowering by repressing the AtNF
      YA transcription factor, which in turn reduces the expression of FLOWERING LOCUS
      C (FLC), allowing for the expression of FLC target genes such as FLOWERING LOCUS
      T (FT) and LEAFY (LFY) to promote flowering. It was shown that the expression of
      genes or miRNAs involved in the other flowering pathways, namely the photoperiod
      (CO), ambient temperature (SVP), ageing (miR156), and gibberelin (SOC1) pathways,
      was not affected in miR169d-overexpressing plants, suggesting that stress-induced
      early flowering is a novel signalling pathway mediated by miR169. 

PMID- 24336446
TI  - Variations on a theme: Polycomb group proteins in plants.
AB  - Polycomb group (PcG) proteins evolved early in evolution, probably in the common
      ancestor of animals and plants. In some unicellular organisms, such as
      Chlamydomonas and Tetrahymena, PcG proteins silence genes in heterochromatin,
      suggesting an ancestral function in genome defence. In angiosperms, the PcG
      system controls many developmental transitions. A PcG function in the
      vernalization response evolved especially in Brassicaceaea. Thus, the role of PcG
      proteins has changed during evolution to match novel needs. Recent studies
      identified many proteins associated with plant PcG protein complexes. Possible
      functions of these interactions are discussed here. We highlight recent findings
      about recruitment of PcG proteins in plants in comparison with animal system.
      Through the new data, a picture emerges in which PcG protein complexes do not
      function in sequential linear pathways but as dynamically interacting networks
      allowing stabilizing feedback loops. We discuss how the interplay between
      different PcG protein complexes can enable establishment, maintenance, and
      epigenetic inheritance of H3K27me3.

PMID- 24336447
TI  - The role of the nucleus accumbens shell in the mediation of the reinforcing
      properties of a safety signal in free-operant avoidance: dopamine-dependent
      inhibitory effects of d-amphetamine.
AB  - Safety signals (SSs) have been shown to reinforce instrumental avoidance behavior
      due to their ability to signal the absence of an aversive event; however, little
      is known of their neural mediation. This study investigated whether infusions of
      d-amphetamine in the nucleus accumbens (Nac), previously shown to potentiate
      responding for appetitive conditioned reinforcers (CRfs), also regulate avoidance
      responding for a SS. Rats were trained on a free-operant task in which lever
      press responses avoided shock and were reinforced with an auditory SS. Rats were
      then cannulated in the Nac core (NacC) or shell (NacS) and infused with d
      amphetamine and, in separate NacS groups, other drugs, before extinction sessions
      with the SS present or absent following responding. Selective effects of d
      amphetamine were found in the NacS, but not in the NacC, when the SS was present
      in the session. A significant increase in response rate during the presentation
      of the SS reflected a disruption of its fear-inhibiting properties. In parallel,
      a decrease in avoidance response rate reflected the reduced influence of the SS
      as a CRf. Inactivation of the NacS reduced avoidance responding only when the SS
      was present in the session, whereas the D1-D2 DA receptor antagonist alpha
      flupenthixol reduced responding both before and during the SS regardless of the
      presence of the SS. Atomoxetine (ATO), a selective noradrenaline reuptake
      inhibitor, had no effect on responding. These results indicate a role for the
      NacS in the mediation of the conditioned reinforcing properties of a SS. These
      effects appear to be modulated by dopaminergic mechanisms but seem distinct from
      those previously reported with food-related CRfs. 

PMID- 24336448
TI  - Media discourses of low carbon housing: The marginalisation of social and
      behavioural dimensions within the British broadsheet press.
AB  - Decarbonising housing is a key UK government policy to mitigate climate change.
      Using discourse analysis, we assess how low carbon housing is portrayed within
      British broadsheet media. Three distinct storylines were identified. Dominating
      the discourse, Zero carbon housing promotes new-build, low carbon houses as
      offering high technology solutions to the climate problem. Retrofitting homes
      emphasises the need to reduce emissions within existing housing, tackling both
      climate change and rising fuel prices. A more marginal discourse, Sustainable
      living, frames low carbon houses as related to individual identities and 'off
      grid' or greener lifestyles. Our analysis demonstrates that technical and
      economic paradigms dominate media discourse on low carbon housing, marginalising
      social and behavioural aspects. 

PMID- 24336452
TI  - Phoning the patient's general practitioner.

PMID- 24336453
TI  - A multicomponent decision tool for prioritising the updating of systematic
      reviews.

PMID- 24336451
TI  - Evolutionary history of the Clostridium difficile pathogenicity locus.
AB  - The symptoms of Clostridium difficile infection are caused by toxins expressed
      from its 19 kb pathogenicity locus (PaLoc). Stable integration of the PaLoc is
      suggested by its single chromosomal location and the clade specificity of its
      different genetic variants. However, the PaLoc is variably present, even among
      closely related strains, and thus resembles a mobile genetic element. Our aim was
      to explain these apparently conflicting observations by reconstructing the
      evolutionary history of the PaLoc. Phylogenetic analyses and annotation of the
      regions spanning the PaLoc were performed using C. difficile population
      representative genomes chosen from a collection of 1,693 toxigenic (PaLoc
      present) and nontoxigenic (PaLoc absent) isolates. Comparison of the core genome
      and PaLoc phylogenies demonstrated an eventful evolutionary history, with
      distinct PaLoc variants acquired clade specifically after divergence. In
      particular, our data suggest a relatively recent PaLoc acquisition in clade 4.
      Exchanges and losses of the PaLoc DNA have also occurred, via long homologous
      recombination events involving flanking chromosomal sequences. The most recent
      loss event occurred ~30 years ago within a clade 1 genotype. The genetic
      organization of the clade 3 PaLoc was unique in containing a stably integrated
      novel transposon (designated Tn6218), variants of which were found at multiple
      chromosomal locations. Tn6218 elements were Tn916-related but nonconjugative and
      occasionally contained genes conferring resistance to clinically relevant
      antibiotics. The evolutionary histories of two contrasting but clinically
      important genetic elements were thus characterized: the PaLoc, mobilized rarely
      via homologous recombination, and Tn6218, mobilized frequently through
      transposition. 

PMID- 24336454
TI  - The Science hoax: poor journalology reflects poor training in peer review.

PMID- 24336455
TI  - Individual hospital data on "never events" to be published every quarter.

PMID- 24336456
TI  - Intakes of anthocyanins and flavones are associated with biomarkers of insulin
      resistance and inflammation in women.
AB  - Although laboratory data suggest that several flavonoid subclasses are involved
      in glucose metabolism, limited clinical and epidemiologic data are available. The
      current study examined associations between habitual intake of flavonoid
      subclasses, insulin resistance, and related inflammatory biomarkers. In a cross
      sectional study of 1997 females aged 18-76 y, intakes of total flavonoids and
      their subclasses (flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids,
      flavonols, flavones) were calculated from food frequency questionnaires using an
      extended USDA database. Fasting serum glucose, insulin, high-sensitivity C
      reactive protein (hs-CRP; n = 1432), plasminogen activator inhibitor-1 (n = 843),
      and adiponectin (n = 1452) concentrations were measured. In multivariable
      analyses, higher anthocyanin and flavone intake were associated with
      significantly lower peripheral insulin resistance [homeostasis model assessment
      of insulin resistance; quintile 5 (Q5) to Q1 = -0.1, P-trend = 0.04 for
      anthocyanins and flavones] as a result of a decrease in insulin concentrations
      (Q5-Q1 = -0.7 MUU/mL, P-trend = 0.02 anthocyanins; Q5-Q1 = -0.5 MUU/mL, P-trend =
      0.02 flavones). Higher anthocyanin intake was also associated with lower hs-CRP
      concentrations (Q5-Q1 = -0.3 mg/L, P-trend = 0.04), whereas those in the highest
      quintile of flavone intake had improved adiponectin concentrations (Q5-Q1 = 0.7
      MUg/L, P-trend = 0.01). Anthocyanin-rich foods were also associated with lower
      insulin and inflammation levels. No significant associations were observed for
      total or other flavonoid subclasses. Higher intakes of both anthocyanins and
      flavones were associated with improvements in insulin resistance and hs-CRP.
      These associations were found with intakes readily achieved in the diet. The
      observed reduction in insulin concentrations was similar to that reported
      previously for other lifestyle factors. Dose-response trials are needed to
      ascertain optimal intakes for the potential reduction of type 2 diabetes risk. 

PMID- 24336457
TI  - Dietary wolfberry supplementation enhances the protective effect of flu vaccine
      against influenza challenge in aged mice.
AB  - Current vaccines for influenza do not fully protect the aged against influenza
      infection. Although wolfberry (goji berry) has been shown to improve immune
      response, including enhanced antibody production, after vaccination in the aged,
      it is not known if this effect would translate to better protection after
      influenza infection, nor is its underlying mechanism well understood. To address
      these issues, we conducted a study using a 2 * 2 design in which aged male mice
      (20-22 mo) were fed a control or a 5% wolfberry diet for 30 d, then immunized
      with an influenza vaccine or saline (control) on days 31 and 52 of the dietary
      intervention, and finally challenged with influenza A/Puerto Rico/8/34 virus.
      Mice fed wolfberry had higher influenza antibody titers and improved symptoms
      (less postinfection weight loss) compared with the mice treated by vaccine alone.
      Furthermore, an in vitro mechanistic study showed that wolfberry supplementation
      enhanced maturation and activity of antigen-presenting dendritic cells (DCs) in
      aged mice, as indicated by phenotypic change in expression of DC activation
      markers major histocompatibility complex class II, cluster of differentiation
      (CD) 40, CD80, and CD86, and functional change in DC production of cytokines
      interleukin-12 and tumor necrosis factor-alpha as well as DC endocytosis. Also,
      adoptive transfer of wolfberry-treated bone marrow DCs (loaded with ovalbumin(323
      339)-peptide) promoted antigen-specific T cell proliferation as well as
      interleukin-4 and interferon-gamma production in CD4(+) T cells. In summary, our
      data indicate that dietary wolfberry enhances the efficacy of influenza
      vaccination, resulting in better host protection to prevent subsequent influenza
      infection; this effect may be partly attributed to improved DC function.

PMID- 24336458
TI  - Breast milk retinol and plasma retinol-binding protein concentrations provide
      similar estimates of vitamin A deficiency prevalence and identify similar risk
      groups among women in Cameroon but breast milk retinol underestimates the
      prevalence of deficiency among young children.
AB  - Breast milk vitamin A (BMVA) has been proposed as an indicator of population
      vitamin A status but has rarely been applied in large-scale surveys or compared
      with conventional vitamin A biomarkers. We assessed the prevalence of, and risk
      factors for, low BMVA and its relation to vitamin A intake, plasma retinol
      binding protein (pRBP), and markers of inflammation in a national survey in
      Cameroon. We randomly selected 30 clusters in each of 3 strata (South, North, and
      Cities). Casual milk samples were collected from approximately 5 women per
      cluster (n = 440). pRBP, plasma C-reactive protein (pCRP), plasma alpha1-acid
      glycoprotein (pAGP), and 24-h vitamin A intake were assessed in 10 women aged 15
      49 y and 10 children aged 12-59 mo per cluster, including a subset of lactating
      women (n = 253). Low BMVA was infrequent: 7.2% (95% CI: 4.7, 9.8) of values were
      <1.05 MUmol/L, and 9.3% (95% CI: 5.8, 12.7) were <8 MUg/g fat, consistent with
      the low prevalence of pRBP <0.78 MUmol/L among women (< 5%) but lower than the
      prevalence of pRBP <0.83 MUmol/L among children (35%). Risk factors for both low
      BMVA and pRBP included living in the North and low maternal education. BMVA was
      positively associated with inflammation-adjusted pRBP among women in the lowest
      vitamin A intake tertile [<115 MUg retinol activity equivalents (RAEs)/d, P <
      0.01] but not in the highest tertile (>644 MUg RAEs/d, P > 0.4). Controlling for
      milk fat, BMVA was negatively associated with pCRP (P < 0.02) but not pAGP (P >
      0.5). BMVA and pRBP provide similar estimates of vitamin A deficiency prevalence
      and identify the same risk groups among women in Cameroon, but BMVA
      underestimates the prevalence of vitamin A deficiency among young children. 

PMID- 24336459
TI  - Highly stable wideband microwave extraction by synchronizing widely tunable
      optoelectronic oscillator with optical frequency comb.
AB  - Optical frequency combs (OFCs), based on mode-locked lasers (MLLs), have
      attracted considerable attention in many fields over recent years. Among the
      applications of OFCs, one of the most challenging works is the extraction of a
      highly stable microwave with low phase noise. Many synchronisation schemes have
      been exploited to synchronise an electronic oscillator with the pulse train from
      a MLL, helping to extract an ultra-stable microwave. Here, we demonstrate novel
      wideband microwave extraction from a stable OFC by synchronising a single widely
      tunable optoelectronic oscillator (OEO) with an OFC at different harmonic
      frequencies, using an optical phase detection technique. The tunable range of the
      proposed microwave extraction extends from 2 GHz to 4 GHz, and in a long-term
      synchronisation experiment over 12 hours, the proposed synchronisation scheme
      provided a rms timing drift of 18 fs and frequency instabilities at 1.2 * 10(
      15)/1 s and 2.2 * 10(-18)/10,000 s.

PMID- 24336460
TI  - Impact of non-constant concentration exposure on lethality of inhaled hydrogen
      cyanide.
AB  - The ten Berge model, also known as the toxic load model, is an empirical approach
      in hazard assessment modeling for estimating the relationship between the
      inhalation toxicity of a chemical and the exposure duration. The toxic load (TL)
      is normally expressed as a function of vapor concentration (C) and duration (t),
      with TL equaling C(n) * t being a typical form. Hypothetically, any combination
      of concentration and time that yields the same "toxic load" will give a constant
      biological response. These formulas have been developed and tested using
      controlled, constant concentration animal studies, but the validity of applying
      these assumptions to time-varying concentration profiles has not been tested.
      Experiments were designed to test the validity of the model under conditions of
      non-constant acute exposure. Male Sprague-Dawley rats inhaled constant or pulsed
      concentrations of hydrogen cyanide (HCN) generated in a nose-only exposure system
      for 5, 15, or 30 min. The observed lethality of HCN for the 11 different C versus
      t profiles was used to evaluate the ability of the model to adequately describe
      the lethality of HCN under the conditions of non-constant inhalation exposure.
      The model was found to be applicable under the tested conditions, with the
      exception of the median lethality of very brief, high concentration,
      discontinuous exposures.

PMID- 24336462
TI  - A fluorescence turn-on sensor for the detection of palladium ions that operates
      through in situ generation of palladium nanoparticles.
AB  - A simple and straightforward fluorescence method for the detection of palladium
      ions at low concentrations has been developed. The mode of operation of the
      sensor involves in situ generation of palladium nanoparticles (PdNPs), which
      promote a selective deiodination reaction of iodo-BODIPY that forms highly
      fluorescent H-BODIPY. 

PMID- 24336461
TI  - Lifetime risk for cardiovascular disease in a Chinese population: the Chinese
      Multi-Provincial Cohort Study.
AB  - BACKGROUND: Lifetime risk estimation is used to predict long-term cardiovascular
      disease (CVD) risk across the entire life span. However, most of the lifetime
      risk estimation came from the studies based on western population. This study
      aimed to assess the lifetime risk of CVD and the impact of risk factors on
      lifetime risk of CVD in Chinese population. DESIGN: Prospective population-based
      cohort study. METHODS: The study sample came from the Chinese Multi-Provincial
      Cohort Study (CMCS), 21,953 participants aged 35 to 84 years without CVD at the
      baseline were included. The modified Kaplan-Meier method was used to calculate
      the lifetime risk of CVD. RESULTS AND CONCLUSIONS: During follow-up years from
      1992 to 2010, 1,280 participants developed acute CVD events and 1,401 died. The
      lifetime CVD risk, up to age 80 for men and women at age 35, were 24.4% and 20.2%
      respectively. A very low lifetime risk was found in individuals with an optimal
      profile of risk factors which modified the effect of aging. By contrast, with two
      or more high risk factors the lifetime risk up to age 80 reached 51.1% for men
      and 38.6% for women at age 35. The integrated status of major CVD risk factors
      can determine lifetime cardiovascular health and CVD risk in Chinese. Early
      prevention with a goal of all risk factors at optimal levels should become the
      priority of CVD prevention in the future.

PMID- 24336463
TI  - Expression and promoter characterization of BbPacC, a pH response transcription
      factor gene of the entomopathogenic fungus Beauveria bassiana.
AB  - To survive, the entomopathogenic fungus Beauveria bassiana, which shows promise
      as a biocontrol agent for a variety of pests, including agricultural and forestry
      pests and vectors of human pathogens, must tailor gene expression to the
      particular pH of its environment. The pH response transcription factor gene
      BbPacC and its flanking sequence were cloned from this fungus. Quantitative
      reverse transcription (RT)-PCR revealed that it is highly induced by alkaline pH
      and salt stress, and the expression level achieved twice that of the housekeeping
      gene gamma-actin. A microfluorometric assay indicated that the 1479 bp promoter
      region could activate the expression of enhanced green fluorescent protein (EGFP)
      under the same conditions. Truncation analysis showed that the 1479, 1274, 1040,
      888 and 742 bp promoters have similar efficiencies in activating expression of
      beta-glucuronidase (GUS). The GUS activities of corresponding transformants
      reached approximately 50 % that of those containing the strong constitutive
      promoter PtrpC. A truncation upstream at the -572 bp position (referenced to the
      translation start codon ATG), however, resulted in a significant loss of GUS
      activity. Both the upstream absences of the -502 and -387 bp positions caused
      almost complete loss of GUS activity. These results suggest that PPacC is an
      efficient, alkaline, and salt-inducible promoter, the core cis-elements are
      mainly located within the -742 to -502 bp region, and promoters equal to or
      longer than 742 bp may be feasible for regulating gene expression in response to
      an ambient pH or salt stress. 

PMID- 24336464
TI  - Characterization of LgnR, an IclR family transcriptional regulator involved in
      the regulation of L-gluconate catabolic genes in Paracoccus sp. 43P.
AB  - Five genes encoding enzymes required for L-gluconate catabolism, together with
      genes encoding components of putative ABC transporters, are located in a cluster
      in the genome of Paracoccus sp. 43P. A gene encoding a transcriptional regulator
      in the IclR family, lgnR, is located in front of the cluster in the opposite
      direction. Reverse transcription PCR analysis indicated that the cluster was
      transcribed as an operon, termed the lgn operon. Two promoters, P(lgnA) and
      P(lgnR), are divergently located in the intergenic region, and transcription from
      these promoters was induced by addition of L-gluconate or D-idonate, a catabolite
      of L-gluconate. Deletion of lgnR resulted in constitutive expression of lgnA,
      lgnH and lgnR, indicating that lgnR encodes a repressor protein for the
      expression of the lgn operon and lgnR itself. Electrophoretic mobility shift
      assay and DNase I footprinting analyses revealed that recombinant LgnR binds to
      both P(lgnA) and P(lgnR), indicating that LgnR represses transcription from these
      promoters by competing with RNA polymerase for binding to these sequences. D
      Idonate was identified as a candidate effector molecule for dissociation of LgnR
      from these promoters. Phylogenetic analysis revealed that LgnR formed a cluster
      with putative proteins from other genome sequences, which is distinct from those
      proteins of known regulatory functions, in the IclR family of transcriptional
      regulators. Additionally, the phylogeny suggests an evolutionary linkage between
      the L-gluconate catabolic pathway and D-galactonate catabolic pathways
      distributed in Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and
      Actinobacteria.

PMID- 24336465
TI  - Correlation between brachial artery flow-mediated dilation and endothelial
      microparticle levels for identifying endothelial dysfunction in children with
      Kawasaki disease.
AB  - BACKGROUND: We investigated vascular endothelial dysfunction by sonographic
      features of flow-mediated dilation (FMD) and circulating endothelial
      microparticles (EMPs) in Kawasaki disease (KD). METHODS: Twenty-eight patients
      with KD were prospectively grouped according to stage of disease: acute,
      subacute, and convalescent. In addition, 28 healthy children and 28 febrile
      children were selected as controls. And cases in the convalescent phase were
      divided into two subgroups: coronary artery lesion (CAL) and no coronary lesion
      (NCAL). CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs were measured by flow
      cytometry; FMD was obtained by sonography. RESULTS: There were significant
      differences in FMD among the five groups. When compared with healthy controls,
      there were significantly greater numbers of CD144(+)/CD42b(-), CD62E(+), and
      CD105(+) EMPs and a higher proportion of CD62E(+) EMPs in KD patients. The
      proportions and numbers of CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs in KD
      patients were not statistically different than in febrile controls. There were no
      significant differences in FMD and EMPs between the CAL and NCAL subgroups. There
      were significantly negative correlations between the values of FMD and EMPs in
      the three phases of KD. CONCLUSION: The increased levels of EMPs have significant
      correlation with decreased values of FMD, both of which may reflect endothelial
      dysfunction in child KD.

PMID- 24336467
TI  - Crohn's disease presenting as bladder mass.

PMID- 24336466
TI  - Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse
      ES cells.
AB  - Mouse embryonic stem (ES) cell cultures exhibit heterogeneity and recently are
      discovered to sporadically enter the 2-cell (2C)-embryo state, critical for ES
      potency. Zscan4 could mark the sporadic 2C-state of ES cells. However, factors
      that regulate the Zscan4(+)/2C state remain to be elucidated. We show that Tbx3
      plays a novel role in regulation of Zscan4(+)/2C state. Tbx3 activates 2-cell
      genes including Zscan4 and Tcstv1/3, but not vise versa. Ectopic expression of
      Tbx3 results in telomere elongation, consistent with a role for Zscan4 in
      telomere lengthening. Mechanistically, Tbx3 decreases Dnmt3b and increases Tet2
      protein levels, and reduces binding of Dnmt3b to subtelomeres, resulting in
      reduced DNA methylation and derepression of genes at subtelomeres, e.g. Zscan4.
      These data suggest that Tbx3 can activate Zscan4(+)/2C state by negative
      regulation of DNA methylation at repeated sequences, linking to telomere
      maintenance and self-renewal of ES cells. 

PMID- 24336468
TI  - Epidemiology of paediatric firearm injuries in the USA, 2001-2010.
AB  - OBJECTIVES: Firearm injuries to children and adolescents remain an important
      cause of morbidity and mortality in the USA. The objectives of this study were to
      describe the prevalence of and epidemiologic risk factors associated with firearm
      injuries to children and adolescents evaluated in a nationally representative
      sample of US emergency departments and ambulatory care centres. STUDY DESIGN: We
      performed a retrospective cross-sectional analysis of data from the National
      Hospital Ambulatory Medical Care Survey from 2001 to 2010. Firearm injury-related
      visits in patients 0-19 years old were identified using the International
      Classification of Diseases, Ninth Revision, Clinical Modification firearm injury
      codes. The primary outcome was the prevalence of firearm-related injuries. We
      used multivariate logistic regression to analyse demographic risk factors
      associated with these injuries. RESULTS: From 2001 to 2010, there were a total of
      322 730 927 (95% CI 287 462 091 to 357 999 763) paediatric US outpatient visits;
      198 969 visits (0.06%, 95% CI 120 727 to 277 211) were for firearm injuries.
      Fatal firearm injuries accounted for 2% of these visits; 36% were intentionally
      inflicted. There were increased odds of firearm injuries to men (OR 10.2, 95% CI
      5.1 to 20.5), black children and adolescents (0-19 years) (OR 3.2, 95% CI 1.5 to
      6.7) and adolescents 12-19 years old (all races) (OR 16.6, 95% CI 6.3 to 44.3) on
      multivariable analysis. CONCLUSIONS: Firearm injuries continue to be a
      substantial problem for US children and adolescents, with non-fatal rates 24%
      higher than previously reported. Increased odds for firearm-related visits were
      found in men, black children and those 12-19 years old.

PMID- 24336469
TI  - Room-temperature Pd-catalyzed C-H chlorination by weak coordination: one-pot
      synthesis of 2-chlorophenols with excellent regioselectivity.
AB  - A room-temperature Pd(II)-catalyzed regioselective chlorination reaction has been
      developed for a facile one-pot synthesis of a broad range of 2-chlorophenols. The
      reaction demonstrates an excellent regioselectivity and reactivity for C-H
      chlorination. This reaction represents one of the rare examples of mild C-H
      functionalization at ambient temperature.

PMID- 24336470
TI  - Identification and quantification of aminophospholipid molecular species on the
      surface of apoptotic and activated cells.
AB  - This protocol measures externalization of aminophospholipids (APLs) to the
      outside of the plasma membrane using mass spectrometry (MS). APL externalization
      occurs in numerous events, and it is relevant for transplant medicine, immunity
      and cancer. In this protocol, externalized APLs are chemically modified by using
      a cell-impermeable reagent (sulfo-NHS-biotin), and then they are isolated via a
      liquid:liquid extraction and quantified by reverse-phase liquid chromatography
      tandem MS (LC-MS/MS) against in-house-generated standards. This protocol
      describes a complementary method to existing assays that are not quantitative
      (e.g., annexin V flow cytometry), and it is applicable to the study of membrane
      reorganization in all cell types during apoptosis (e.g., during development,
      cancer, psychiatric disorders and other conditions, aging, vesiculation and cell
      division). The protocol takes ~2-4 d, including the generation of standards. 

PMID- 24336471
TI  - Resin-assisted enrichment of thiols as a general strategy for proteomic profiling
      of cysteine-based reversible modifications.
AB  - Reversible modifications of cysteine thiols have a key role in redox signaling
      and regulation. A number of reversible redox modifications, including disulfide
      formation, S-nitrosylation (SNO) and S-glutathionylation (SSG), have been
      recognized for their significance in various physiological and pathological
      processes. Here we describe a procedure for the enrichment of peptides containing
      reversible cysteine modifications. Starting with tissue or cell lysate samples,
      all of the unmodified free thiols are blocked using N-ethylmaleimide (NEM). This
      is followed by the selective reduction of those cysteines bearing the reversible
      modification(s) of interest. The reduction is achieved by using different
      reducing reagents that react specifically with each type of cysteine modification
      (e.g., ascorbate for SNO). This protocol serves as a general approach for
      enrichment of thiol-containing proteins or peptides derived from reversibly
      modified proteins. The approach uses a commercially available thiol-affinity
      resin (thiopropyl Sepharose 6B) to directly capture free thiol-containing
      proteins through a disulfide exchange reaction, followed by on-resin protein
      digestion and multiplexed isobaric labeling to facilitate liquid chromatography
      tandem mass spectrometry (LC-MS/MS)-based quantitative site-specific analysis of
      cysteine-based reversible modifications. The overall approach requires a simpler
      workflow with increased specificity compared with the commonly used biotinylation
      based assays. The procedure for selective enrichment and analyses of SNO and the
      level of total reversible cysteine modifications (or total oxidation) is
      presented to demonstrate the utility of this general strategy. The entire
      protocol requires ~3 d for sample processing with an additional day for LC-MS/MS
      and data analysis. 

PMID- 24336472
TI  - Live-cell imaging of receptors around postsynaptic membranes.
AB  - This protocol describes how to image the trafficking of glutamate receptors
      around excitatory postsynaptic membrane formed on an adhesion protein-coated
      glass surface. The protocol was developed to clarify how receptors move during
      the induction of synaptic plasticity. Dissociated neurons are cultured on a
      coverslip coated with neurexin, which induces the formation of postsynaptic
      membrane-like structures on the glass surface. A glutamate receptor tagged with a
      fluorescent protein is then transfected into neurons, and it is observed with
      total internal reflection fluorescence microscopy. The whole process takes about
      3 weeks. Changes in the amount of cell-surface receptors caused by neuronal
      activities can be quantified, and individual exocytosis events of receptors can
      be clearly observed around the pseudo-postsynaptic membrane. This protocol has
      potential applications for studies of movements of membrane proteins around other
      specialized regions of the cell membrane, such as the inhibitory postsynaptic
      membrane, the presynaptic membrane or the immunological synapses. 

PMID- 24336473
TI  - Discovery of protein interactions using parallel analysis of translated ORFs
      (PLATO).
AB  - Parallel analysis of translated open reading frames (ORFs) (PLATO) can be used
      for the unbiased discovery of interactions between full-length proteins encoded
      by a library of 'prey' ORFs and surface-immobilized 'bait' antibodies,
      polypeptides or small-molecular-weight compounds. PLATO uses ribosome display
      (RD) to link ORF-derived mRNA molecules to the proteins they encode, and
      recovered mRNA from affinity enrichment is subjected to analysis using massively
      parallel DNA sequencing. Compared with alternative in vitro methods, PLATO
      provides several advantages including library size and cost. A unique advantage
      of PLATO is that an alternative reverse transcription-quantitative PCR (RT-qPCR)
      protocol can be used to test binding of specific, individual proteins. To
      illustrate a typical experimental workflow, we demonstrate PLATO for the
      identification of the immune target of serum antibodies from patients with
      inclusion body myositis (IBM). Beginning with an ORFeome library in an RD vector,
      the protocol can produce samples for deep sequencing or RT-qPCR within 4 d. 

PMID- 24336474
TI  - Copper-catalyzed asymmetric conjugate addition of alkylzirconium reagents to
      cyclic enones to form quaternary centers.
AB  - This protocol describes the catalytic asymmetric formation of all-carbon
      quaternary centers--a distinctive feature of many natural products and
      pharmaceuticals--via conjugate addition of alkylzirconium reagents to a tertiary
      enone. This methodology uses alkenes as starting materials and enables the
      incorporation of functional groups. The alkylzirconium reagent is generated in
      situ by mixing the alkene with the Schwartz reagent. The alkylzirconium is added
      to a solution containing a copper-ligand complex, and then the enone is added to
      the mixture. The addition of pent-4-en-1-ylbenzene to 3-methyl-2-cyclohexenone is
      detailed herein as a generic example. This procedure works at room temperature
      (~25  degrees C), and it is scalable to at least 1.5 g. The setup of the reaction
      takes 3-5 h and the reaction goes to completion within 4-20 h.

PMID- 24336475
TI  - Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation
      and ring-opening cascade.
AB  - An enantioselective epoxidation of tryptophols followed by an intramolecular
      epoxide opening reaction was realized by chiral vanadium catalysts derived from
      C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline
      derivatives with up to 89% yield and 90% ee were obtained under mild reaction
      conditions.

PMID- 24336476
TI  - Proposed guidelines for international clinical education in US-based physical
      therapist education programs: results of a focus group and Delphi Study.
AB  - BACKGROUND: Physical therapist students are increasingly engaging in
      international clinical education (ICE). The growth of international engagement
      has been accompanied by appeals to ensure that these experiences are conducted in
      an ethical manner. Although detailed guidelines have been developed to guide
      global health training in general, they do not specifically address all aspects
      relevant to ICE in physical therapist education. OBJECTIVE: The purpose of this
      study was to systematically develop recommendations for the implementation of ICE
      in physical therapist education to promote ethical practice. METHODS: An initial
      virtual focus group of 5 physical therapist faculty with expertise in ICE
      provided input to review and revise global health training guidelines previously
      developed by non-physical therapists. The revised guidelines were distributed to
      a pool of 19 physical therapist faculty with ICE experience for additional review
      and revision through 3 online Delphi survey rounds. RESULTS: The participants
      accepted 31 of the original guidelines with or without revisions, rejected 2
      guidelines, and developed 10 new guidelines or subguidelines. Most notably, they
      rejected a guideline related to students pursuing training outside of a
      structured program, stressing that ICE should never be done outside of a formal
      program. LIMITATIONS: The primary limitation is that the study included only
      faculty from sending institutions and thus lacked the voices of the host
      institutions, students, partner organizations, or funders. CONCLUSIONS: This
      study systematically produced guidelines for ICE in physical therapist education
      using a range of ICE experts from sending institutions. The recommendations may
      be used by educators and other decision makers to optimally design new ICE
      opportunities or to improve existing ones. Additional validation should be done
      to ensure relevance for all stakeholders.

PMID- 24336477
TI  - Comparison of mulligan sustained natural apophyseal glides and maitland
      mobilizations for treatment of cervicogenic dizziness: a randomized controlled
      trial.
AB  - BACKGROUND: There is short-term evidence for treatment of cervicogenic dizziness
      with Mulligan sustained natural apophyseal glides (SNAGs) but no evidence for
      treatment with Maitland mobilizations. OBJECTIVE: The purpose of this study was
      to compare the effectiveness of SNAGs and Maitland mobilizations for cervicogenic
      dizziness. DESIGN: A double-blind, parallel-arm randomized controlled trial was
      conducted. SETTING: The study was conducted at a university in Newcastle,
      Australia. PARTICIPANTS: Eighty-six people with cervicogenic dizziness were the
      study participants. INTERVENTIONS: Included participants were randomly allocated
      to receive 1 of 3 interventions: Mulligan SNAGs (including self-administered
      SNAGs), Maitland mobilizations plus range-of-motion exercises, or placebo.
      MEASUREMENTS: The primary outcome measure was intensity of dizziness. Other
      outcome measures were: frequency of dizziness, the Dizziness Handicap Inventory
      (DHI), intensity of pain, and global perceived effect (GPE). RESULTS: Both manual
      therapy groups had reduced dizziness intensity and frequency posttreatment and at
      12 weeks compared with baseline. There was no change in the placebo group. Both
      manual therapy groups had less dizziness intensity posttreatment (SNAGs: mean
      difference=-20.7, 95% confidence interval [95% CI]=-33.6, -7.7; mobilizations:
      mean difference=-15.2, 95% CI=-27.9, -2.4) and at 12 weeks (SNAGs: mean
      difference=-18.4, 95% CI=-31.3, -5.4; mobilizations: mean difference=-14.4, 95%
      CI=-27.4, -1.5) compared with the placebo group. Compared with the placebo group,
      both the SNAG and Maitland mobilization groups had less frequency of dizziness at
      12 weeks. There were no differences between the 2 manual therapy interventions
      for these dizziness measures. For DHI and pain, all 3 groups improved
      posttreatment and at 12 weeks. Both manual therapy groups reported a higher GPE
      compared with the placebo group. There were no treatment-related adverse effects
      lasting longer than 24 hours. LIMITATIONS: The therapist performing the
      interventions was not blind to group allocation. CONCLUSIONS: Both SNAGs and
      Maitland mobilizations provide comparable immediate and sustained (12 weeks)
      reductions in intensity and frequency of chronic cervicogenic dizziness.

PMID- 24336478
TI  - Broad approach is needed to reduce gun violence, US psychologists say.

PMID- 24336479
TI  - Xiphoid syndrome: an uncommon occupational disorder.
AB  - We report a case of a 45-year-old man, complaining of swelling and pain in his
      epigastric region for the last 3 years. According to his medical history, he had
      undergone various investigations and treatments for gastro-oesophageal reflux,
      without relief. He had had a history of chronic repeated microtraumas to his
      sternum during 9 years of working as a carpenter, as a result of placing wood
      against his anterior chest wall and pushing the former into a plank cutting
      machine. On examination, a tender swelling was palpable as an immobile, hard mass
      showing minimal protrusion under the skin on the xiphoid process. He was
      diagnosed as having xiphoid syndrome. We prescribed anti-inflammatory medication
      and advised him to avoid pressure on his anterior chest wall, especially on the
      sternum, while cutting wood. At follow-up, the symptoms were relieved. Xiphoid
      syndrome may be seen in people performing hard physical work who incur sustained
      pressure or friction on their anterior chest wall. The case emphasizes the
      importance of the occupational history as well as clinical and radiological
      investigation of unusual conditions as mentioned above. 

PMID- 24336480
TI  - Symptoms of craniomandibular dysfunction in professional orchestra musicians.
AB  - BACKGROUND: Up to 80% of professional musicians are affected by playing-related
      musculoskeletal disorders, but data regarding the frequency of craniomandibular
      dysfunction (CMD) in professional orchestra musicians is scarce. AIMS: To
      evaluate the frequency of CMD and its relation to musculoskeletal pain in various
      body regions. METHODS: A questionnaire-based survey approach assessing CMD
      symptoms and musculoskeletal pain in professional orchestra players was adopted.
      Relative prevalence rates and prevalence ratios for different instrument groups
      were estimated. RESULTS: A total of 408 musicians completed the questionnaire
      (response rate 57%). Playing-related pain in the teeth or jaw was reported by 19
      47% of musicians and TMJ pain by 15-34%, depending on the instrument group.
      Current pain in the face indicating a painful CMD was reported in 6-10% and
      related symptoms such as teeth grinding in 25-34%, jaw clenching in 33-42% and
      jaw locking in 11-18% of musicians. Females were 2.4 times (95% confidence
      intervals (CI) 1.49-3.84) more likely to report having had orofacial pain within
      the last month. Musicians reporting orofacial pain within the last month were 4.8
      times (95% CI: 2.83-8.02) more likely to report pain in the neck and 2.5-3.8
      times (P < 0.05) more likely to report pain in other body regions, including
      shoulders, right wrist, left fingers and the thoracic and lumbar spine.
      CONCLUSIONS: Symptoms suggesting CMD were common in this study of professional
      orchestra musicians and were associated with pain in the neck, shoulder and
      hands. There is a need to enhance awareness of CMD to optimize early medical
      diagnosis and treatment.

PMID- 24336481
TI  - Acceptance and decision making in amyotrophic lateral sclerosis from a life
      course perspective.
AB  - Researchers have explored perceptions of health care services among people with
      amyotrophic lateral sclerosis (ALS), but little is known about how and why people
      with ALS engage with services. We undertook a grounded theory study to identify
      key psychosocial processes that underpin how and why people with ALS engage with
      health care services. We conducted in-depth interviews with 34 participants
      sampled from the Irish ALS population-based register. We found that age and life
      stage shaped participants' decision making about care. Participants in later life
      were more accepting of ALS and of death than young and middle-aged participants.
      Family was the primary context to how participants engaged with services, and
      their decisions about care were shaped by parenthood at different life stages.
      Health care professionals need to be attuned to the impact of life-course
      trajectories and family relations on the decisions people with ALS make about
      their care. 

PMID- 24336482
TI  - The standing pool of genomic structural variation in a natural population of
      Mimulus guttatus.
AB  - Major unresolved questions in evolutionary genetics include determining the
      contributions of different mutational sources to the total pool of genetic
      variation in a species, and understanding how these different forms of genetic
      variation interact with natural selection. Recent work has shown that structural
      variants (SVs) (insertions, deletions, inversions, and transpositions) are a
      major source of genetic variation, often outnumbering single nucleotide variants
      in terms of total bases affected. Despite the near ubiquity of SVs, major
      questions about their interaction with natural selection remain. For example, how
      does the allele frequency spectrum of SVs differ when compared with single
      nucleotide variants? How often do SVs affect genes, and what are the
      consequences? To begin to address these questions, we have systematically
      identified and characterized a large set of submicroscopic insertion and deletion
      (indel) variants (between 1 and 200 kb in length) among ten inbred lines from a
      single natural population of the plant species Mimulus guttatus. After extensive
      computational filtering, we focused on a set of 4,142 high-confidence indels that
      showed an experimental validation rate of 73%. All but one of these indels were
      less than 200 kb. Although the largest were generally at lower frequencies in the
      population, a surprising number of large indels are at intermediate frequencies.
      Although indels overlapping with genes were much rarer than expected by chance,
      approximately 600 genes were affected by an indel. Nucleotide-binding site
      leucine-rich repeat (NBS-LRR) defense response genes were the most enriched among
      the gene families affected. Most indels associated with genes were rare and
      appeared to be under purifying selection, though we do find four high-frequency
      derived insertion alleles that show signatures of recent positive selection. 

PMID- 24336483
TI  - Structural basis of a nucleosome containing histone H2A.B/H2A.Bbd that
      transiently associates with reorganized chromatin.
AB  - Human histone H2A.B (formerly H2A.Bbd), a non-allelic H2A variant, exchanges
      rapidly as compared to canonical H2A, and preferentially associates with actively
      transcribed genes. We found that H2A.B transiently accumulated at DNA replication
      and repair foci in living cells. To explore the biochemical function of H2A.B, we
      performed nucleosome reconstitution analyses using various lengths of DNA. Two
      types of H2A.B nucleosomes, octasome and hexasome, were formed with 116, 124, or
      130 base pairs (bp) of DNA, and only the octasome was formed with 136 or 146 bp
      DNA. In contrast, only hexasome formation was observed by canonical H2A with 116
      or 124 bp DNA. A small-angle X-ray scattering analysis revealed that the H2A.B
      octasome is more extended, due to the flexible detachment of the DNA regions at
      the entry/exit sites from the histone surface. These results suggested that H2A.B
      rapidly and transiently forms nucleosomes with short DNA segments during
      chromatin reorganization. 

PMID- 24336484
TI  - Lava flow hazards at Mount Etna: constraints imposed by eruptive history and
      numerical simulations.
AB  - Improving lava flow hazard assessment is one of the most important and
      challenging fields of volcanology, and has an immediate and practical impact on
      society. Here, we present a methodology for the quantitative assessment of lava
      flow hazards based on a combination of field data, numerical simulations and
      probability analyses. With the extensive data available on historic eruptions of
      Mt. Etna, going back over 2000 years, it has been possible to construct two
      hazard maps, one for flank and the other for summit eruptions, allowing a
      quantitative analysis of the most likely future courses of lava flows. The
      effective use of hazard maps of Etna may help in minimizing the damage from
      volcanic eruptions through correct land use in densely urbanized area with a
      population of almost one million people. Although this study was conducted on Mt.
      Etna, the approach used is designed to be applicable to other volcanic areas. 

PMID- 24336485
TI  - Percutaneous endoscopic gastrostomy tube replacement unexpected serious events.
AB  - Percutaneous endoscopic gastrostomy tubes are replaced due to clogging, breaking,
      and dislodgement. There are potential complications associated with these
      procedures, including intraperitoneal placement of the tube and peritonitis,
      which can occur even in the presence of a well established stoma site. Herein we
      present a case series of 3 patients with mature gastrocutaneous tracks, who
      developed peritonitis following tube replacement. In the absence of a consensus
      or international guidelines regarding the management of patients requiring
      percoutaneous endoscopic gastrostomy tube replacement, emphasis should be given
      on prevention of severe adverse events and on early anticipation of their
      occurrence. Clinical experience indicates that recognition of high-risk
      procedures, selection of the appropriate replacement method and confirmation of
      correct tube placement can improve patients' safety and reduce the complications
      rate. 

PMID- 24336486
TI  - Nutrition supplements for athletes: potential application to malnutrition.

PMID- 24336487
TI  - Sulfate templated assembly of neutral receptors in aqueous DMSO - orthogonal
      versus biplane structures.
AB  - Simple, easily available diamidocarbazoles form robust 2 : 1 complexes with SO4(2
      ) even in the presence of a large excess of water. An appropriate choice of side
      arms directs the assembly towards the formation of either an orthogonal or a
      biplane structure, both in solution and in the solid state.

PMID- 24336488
TI  - Defects in bilayer silica and graphene: common trends in diverse hexagonal two
      dimensional systems.
AB  - By combining first-principles and classical force field calculations with
      aberration-corrected high-resolution transmission electron microscopy
      experiments, we study the morphology and energetics of point and extended defects
      in hexagonal bilayer silica and make comparison to graphene, another two
      dimensional (2D) system with hexagonal symmetry. We show that the motifs of
      isolated point defects in these 2D structures with otherwise very different
      properties are similar, and include Stone-Wales-type defects formed by structural
      unit rotations, flower defects and reconstructed double vacancies. The morphology
      and energetics of extended defects, such as grain boundaries have much in common
      as well. As both sp(2)-hybridised carbon and bilayer silica can also form
      amorphous structures, our results indicate that the morphology of imperfect 2D
      honeycomb lattices is largely governed by the underlying symmetry of the lattice.

PMID- 24336489
TI  - In vivo ratiometric Zn2+ imaging in zebrafish larvae using a new visible light
      excitable fluorescent sensor.
AB  - A visible light excitable ratiometric Zn(2+) sensor was developed by integrating
      a Zn(2+) chelator as the ICT donor of the fluorophore sulfamoylbenzoxadiazole,
      which displays the Zn(2+)-induced hypsochromic emission shift (40 nm) and favors
      the in vivo ratiometric Zn(2+) imaging in zebrafish larvae. 

PMID- 24336490
TI  - Tumour microenvironment: losing your SPARC.

PMID- 24336493
TI  - Vascularization and nutrient delivery at root-knot nematode feeding sites in host
      roots.
AB  - Plants are constantly challenged by pathogens and pests, which can have a
      profound impact on the yield and quality of produce in agricultural systems. The
      vascular system of higher plants is critical for growth and for their ability to
      counteract changing external conditions, serving as a distribution network for
      water, nutrients, and photosynthates from the source organs to regions where they
      are in demand. Unfortunately, these features also make it an attractive target
      for pathogens and pests that demand access to a reliable supply of host
      resources. The vascular tissue of plants therefore often plays a central role in
      pathogen and parasite interactions. One of the more striking rearrangements of
      the host vascular system occurs during root-knot nematode infestation of plant
      roots. These sedentary endoparasites induce permanent feeding sites that are
      comprised of 'giant cells' and are subject to extensive changes in
      vascularization, resulting in the giant cells being encaged within a network of
      de novo formed xylem and phloem cells. Despite being considered critical to the
      function of the feeding site, the mechanisms underlying this vascularization have
      received surprisingly little attention when compared with the amount of research
      on giant cell development and function. An overview of the current knowledge on
      vascularization of root-knot nematode feeding sites is provided here and recent
      advances in our understanding of the transport mechanisms involved in nutrient
      delivery to these parasite-induced sinks are described. 

PMID- 24336492
TI  - Opposite action of R2R3-MYBs from different subgroups on key genes of the
      shikimate and monolignol pathways in spruce.
AB  - Redundancy and competition between R2R3-MYB activators and repressors on common
      target genes has been proposed as a fine-tuning mechanism for the regulation of
      plant secondary metabolism. This hypothesis was tested in white spruce [Picea
      glauca (Moench) Voss] by investigating the effects of R2R3-MYBs from different
      subgroups on common targets from distinct metabolic pathways. Comparative
      analysis of transcript profiling data in spruces overexpressing R2R3-MYBs from
      loblolly pine (Pinus taeda L.), PtMYB1, PtMYB8, and PtMYB14, defined a set of
      common genes that display opposite regulation effects. The relationship between
      the closest MYB homologues and 33 putative target genes was explored by
      quantitative PCR expression profiling in wild-type P. glauca plants during the
      diurnal cycle. Significant Spearman's correlation estimates were consistent with
      the proposed opposite effect of different R2R3-MYBs on several putative target
      genes in a time-related and tissue-preferential manner. Expression of sequences
      coding for 4CL, DHS2, COMT1, SHM4, and a lipase thio/esterase positively
      correlated with that of PgMYB1 and PgMYB8, but negatively with that of PgMYB14
      and PgMYB15. Complementary electrophoretic mobility shift assay (EMSA) and
      transactivation assay provided experimental evidence that these different R2R3
      MYBs are able to bind similar AC cis-elements in the promoter region of Pg4CL and
      PgDHS2 genes but have opposite effects on their expression. Competitive binding
      EMSA experiments showed that PgMYB8 competes more strongly than PgMYB15 for the
      AC-I MYB binding site in the Pg4CL promoter. Together, the results bring a new
      perspective to the action of R2R3-MYB proteins in the regulation of distinct but
      interconnecting metabolism pathways. 

PMID- 24336494
TI  - Appraising medicines: improving but not perfect.

PMID- 24336491
TI  - The roles of K(+) channels in cancer.
AB  - Potassium channels are transmembrane proteins that selectively facilitate the
      flow of potassium ions down an electrochemical gradient. These molecules have
      been studied in great detail in the context of cell excitability, but their roles
      in less cell type-specific functions, such as cell proliferation, angiogenesis or
      cell migration, have only recently been assessed. Moreover, the importance of
      these channels for tumour biology has become evident. This, coupled with the fact
      that they are accessible proteins and that their pharmacology is well
      characterized, has increased the interest in investigating potassium channels as
      therapeutic targets in cancer patients. 

PMID- 24336496
TI  - Drug assessment: UK style.
AB  - Before medicines can be marketed in the UK, they are subject to a system of
      licensing and the granting of a marketing authorisation that describes the
      conditions and patient groups for which the medicinal product can be used within
      the terms of its licence.(1) The licensing process involves an assessment of data
      relating to the efficacy, safety and quality of the product. However, the
      marketing authorisation does not determine whether, or how, it will be used in
      clinical practice. In the UK, the National Institute for Health and Care
      Excellence (NICE), the Scottish Medicines Consortium (SMC) and the All Wales
      Medicines Strategy Group (AWMSG) publish recommendations on the use of medicines
      for health services in the United Kingdom. In this article we review their remit,
      work processes and the status of guidance published in England, Scotland, Wales
      and Northern Ireland. 

PMID- 24336497
TI  - Clinical commissioning groups serve too many masters, finds study.

PMID- 24336498
TI  - Targeted-capture massively-parallel sequencing enables robust detection of
      clinically informative mutations from formalin-fixed tumours.
AB  - Massively parallel sequencing offers the ability to interrogate a tumour biopsy
      for multiple mutational changes. For clinical samples, methodologies must enable
      maximal extraction of available sequence information from formalin-fixed and
      paraffin-embedded (FFPE) material. We assessed the use of targeted capture for
      mutation detection in FFPE DNA. The capture probes targeted the coding region of
      all known kinase genes and selected oncogenes and tumour suppressor genes. Seven
      melanoma cell lines and matching FFPE xenograft DNAs were sequenced. An
      informatics pipeline was developed to identify variants and contaminating mouse
      reads. Concordance of 100% was observed between unfixed and formalin-fixed for
      reported COSMIC variants including BRAF V600E. mutations in genes not
      conventionally screened including ERBB4, ATM, STK11 and CDKN2A were readily
      detected. All regions were adequately covered with independent reads regardless
      of GC content. This study indicates that hybridisation capture is a robust
      approach for massively parallel sequencing of FFPE samples. 

PMID- 24336499
TI  - Identification of novel modifiers of Abeta toxicity by transcriptomic analysis in
      the fruitfly.
AB  - The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here,
      we study the relationship between ageing and AD using a systems biology approach
      that employs a Drosophila (fruitfly) model of AD in which the flies overexpress
      the human Abeta42 peptide. We identified 712 genes that are differentially
      expressed between control and Abeta-expressing flies. We further divided these
      genes according to how they change over the animal's lifetime and discovered that
      the AD-related gene expression signature is age-independent. We have identified a
      number of differentially expressed pathways that are likely to play an important
      role in the disease, including oxidative stress and innate immunity. In
      particular, we uncovered two new modifiers of the Abeta phenotype, namely Sod3
      and PGRP-SC1b. 

PMID- 24336500
TI  - Solution-phase-peptide synthesis via the group-assisted purification (GAP)
      chemistry without using chromatography and recrystallization.
AB  - The solution phase synthesis of N-protected amino acids and peptides has been
      achieved through the Group-Assisted Purification (GAP) chemistry by avoiding
      disadvantages of other methods in regard to the difficult scale-up, expenses of
      solid and soluble polymers, etc. The GAP synthesis can reduce the use of
      solvents, silica gels, energy and manpower. In addition, the GAP auxiliary can be
      conveniently recovered for re-use and is environmentally friendly and benign, and
      substantially reduces waste production in academic labs and industry. 

PMID- 24336501
TI  - The ginger-shaped asteroid 4179 Toutatis: new observations from a successful
      flyby of Chang'e-2.
AB  - On 13 December 2012, Chang'e-2 conducted a successful flyby of the near-Earth
      asteroid 4179 Toutatis at a closest distance of 770 +/- 120 meters from the
      asteroid's surface. The highest-resolution image, with a resolution of better
      than 3 meters, reveals new discoveries on the asteroid, e.g., a giant basin at
      the big end, a sharply perpendicular silhouette near the neck region, and direct
      evidence of boulders and regolith, which suggests that Toutatis may bear a rubble
      pile structure. Toutatis' maximum physical length and width are (4.75 * 1.95 km)
      +/-10%, respectively, and the direction of the +z axis is estimated to be (250 +/
      5 degrees , 63 +/- 5 degrees ) with respect to the J2000 ecliptic coordinate
      system. The bifurcated configuration is indicative of a contact binary origin for
      Toutatis, which is composed of two lobes (head and body). Chang'e-2 observations
      have significantly improved our understanding of the characteristics, formation,
      and evolution of asteroids in general. 

PMID- 24336502
TI  - Viral diseases: Zeroing in on RSV vaccine design.

PMID- 24336503
TI  - Obesity and diabetes: Two-for-one strike at incretins.

PMID- 24336505
TI  - Neurodegenerative disease: Yeast cells reveal new target for Parkinson's disease.

PMID- 24336507
TI  - Edge-closed graphene nanoribbons fabricated by spontaneous collapse of few-walled
      carbon nanotubes.
AB  - A simple method of fabricating graphene nanoribbons (GNRs) with closed edges by
      utilizing the spontaneous collapsing mechanism of few-walled carbon nanotubes
      (CNTs) is demonstrated. The diameter of the tube that can be used to fabricate
      GNRs should be larger than a critical value, which is 16.27, 24.41 and 39.15 A
      for single-, double- and triple-walled CNTs, respectively. The geometry of
      fabricated multi-layered GNRs consists of two highly strained bulbs on the two
      edges and a flat region with an interlayer distance of 3.4 A. Defects at the
      initial tube wall affect the collapsing speed and GNR configuration. The
      encapsulated molecules slow the collapsing speed, and may even hinder the
      collapse of the tube. 

PMID- 24336506
TI  - Label-free luminescence switch-on detection of T4 polynucleotide kinase activity
      using a G-quadruplex-selective probe.
AB  - A label-free, oligonucleotide-based, switch-on luminescence detection method for
      T4 polynucleotide kinase activity has been developed using a novel G-quadruplex
      selective luminescent Ir(iii) complex probe. The application of the assay for
      screening potential T4 PNK inhibitors is also demonstrated. To our knowledge,
      this is the first metal-based assay for PNK activity. 

PMID- 24336508
TI  - Li ion dynamics in TiO2 anode materials with an ordered hierarchical pore
      structure--insights from ex situ NMR.
AB  - Ex situ Nuclear Magnetic Resonance (NMR) measurements were carried out to study
      lithium ion dynamics in lithium intercalated mesoporous anatase (LixTiO2) serving
      as an anode material for rechargeable lithium-ion batteries. As has been shown
      recently, hierarchically ordered TiO2 shows excellent cycling performance and
      ensures a high lithium storage capacity. (7)Li spin-lattice relaxation NMR and
      stimulated echo NMR serve as a powerful combination to shed light on the Li
      hopping processes from an atomic-scale point of view. To determine atomic Li jump
      rates and microscopic activation energies temperature-variable SLR NMR
      measurements, in both the laboratory and rotating frame of reference, as well as
      mixing-time dependent spin-alignment echo NMR measurements were carried out. The
      results point to moderate Li diffusivities; however, in a lithium-ion cell this
      is compensated for by taking advantage of nm-structured materials with greatly
      reduced diffusion lengths. Importantly, although a phase transition from
      tetragonal symmetry to orthorhombic symmetry takes place at increased states of
      charge, the diffusion parameters and activation energies probed (0.4 to 0.5 eV)
      do depend weaker on Li content x than expected. Thus, despite the increased value
      of x, the evolution of the orthorhombic phase seems to support Li diffusivity
      rather than to affect the transport properties in a negative way. This
      interesting feature might be highly beneficial for the excellent cycling behavior
      observed recently. 

PMID- 24336504
TI  - The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and
      cancer treatment.
AB  - The Hippo signalling pathway is an emerging growth control and tumour suppressor
      pathway that regulates cell proliferation and stem cell functions. Defects in
      Hippo signalling and hyperactivation of its downstream effectors Yes-associated
      protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ)
      contribute to the development of cancer, which suggests that pharmacological
      inhibition of YAP and TAZ activity may be an effective anticancer strategy.
      Conversely, YAP and TAZ can also have beneficial roles in stimulating tissue
      repair and regeneration following injury, so their activation may be
      therapeutically useful in these contexts. A complex network of intracellular and
      extracellular signalling pathways that modulate YAP and TAZ activities have
      recently been identified. Here, we review the regulation of the Hippo signalling
      pathway, its functions in normal homeostasis and disease, and recent progress in
      the identification of small-molecule pathway modulators. 

PMID- 24336509
TI  - Integrated enzyme reactor and high resolving chromatography in "sub-chip"
      dimensions for sensitive protein mass spectrometry.
AB  - Reliable, sensitive and automatable analytical methodology is of great value in
      e.g. cancer diagnostics. In this context, an on-line system for enzymatic
      cleavage of proteins, subsequent peptide separation by liquid chromatography (LC)
      with mass spectrometric detection has been developed using "sub-chip" columns (10
      20 MUm inner diameter, ID). The system could detect attomole amounts of isolated
      cancer biomarker progastrin-releasing peptide (ProGRP), in a more automatable
      fashion compared to previous methods. The workflow combines protein digestion
      using an 20 MUm ID immobilized trypsin reactor with a polymeric layer of 2
      hydroxyethyl methacrylate-vinyl azlactone (HEMA-VDM), desalting on a polystyrene
      divinylbenzene (PS-DVB) monolithic trap column, and subsequent separation of
      resulting peptides on a 10 MUm ID (PS-DVB) porous layer open tubular (PLOT)
      column. The high resolution of the PLOT columns was maintained in the on-line
      system, resulting in narrow chromatographic peaks of 3-5 seconds. The trypsin
      reactors provided repeatable performance and were compatible with long-term
      storage. 

PMID- 24336510
TI  - The simplicity of planar networks.
AB  - Shortest paths are not always simple. In planar networks, they can be very
      different from those with the smallest number of turns--the simplest paths. The
      statistical comparison of the lengths of the shortest and simplest paths provides
      a non trivial and non local information about the spatial organization of these
      graphs. We define the simplicity index as the average ratio of these lengths and
      the simplicity profile characterizes the simplicity at different scales. We
      measure these metrics on artificial (roads, highways, railways) and natural
      networks (leaves, slime mould, insect wings) and show that there are fundamental
      differences in the organization of urban and biological systems, related to their
      function, navigation or distribution: straight lines are organized hierarchically
      in biological cases, and have random lengths and locations in urban systems. In
      the case of time evolving networks, the simplicity is able to reveal important
      structural changes during their evolution.

PMID- 24336511
TI  - What do we really know about infants who attend Accident and Emergency
      departments?
AB  - AIMS: Accident and Emergency attendances continue to rise. Infants are
      disproportionately represented. This study examines the clinical reasons infants
      attend UK Accident and Emergency departments. METHODS: A retrospective review of
      6,667 infants aged less than one year attending Accident and Emergency at two
      district general hospitals in London from 1(st) April 2009 to 30(th) March 2010.
      All infants had been assigned to a diagnostic category by the medical coding
      department according to National Health Service (NHS) data guidelines, based on
      the clinical diagnoses stated in the medical records. The Accident and Emergency
      case notes of a random subsample of 10% of infants in each of the top five
      recorded diagnostic categories (n = 535) were reviewed in detail and audited
      against the standard national NHS data set. RESULTS: The top 5 clinical diagnoses
      were 'infectious diseases', 'gastrointestinal', 'respiratory', 'unclassifiable'
      and 'no abnormality detected' (NAD). A third of infants were originally given a
      diagnosis of unclassifiable (21.5%) or NAD (11.5%). After detailed case-note
      review, we were able to reduce this to 9.7% (95% confidence interval (CI): 9.0,
      10.4) and 8.8% (95% CI: 8.1, 9.5), respectively. CONCLUSION: This study
      demonstrates the importance of providing a clear clinical diagnosis and coding
      system for Accident and Emergency attendances and understanding that system
      fully. This would allow for better informed health service evaluation, planning
      and research as each of these relies on the interpretation of routine health-care
      data. Furthermore, the relatively high proportion (10%) of infants attending with
      no discernible underlying medical abnormality suggests the health needs of a
      significant proportion of infants attending Accident and Emergency departments
      may be better addressed by alternative service provision and/or improved
      education and support to parents.

PMID- 24336513
TI  - Enhanced cellular uptake of amphiphilic gold nanoparticles with ester
      functionality.
AB  - Gold nanoparticles (AuNPs) coated with ester-headed or ether-headed PEG ligands
      were synthesized. Ester-headed AuNPs, but not ether-headed, were transferred from
      the organic phase (CH2Cl2) to the alkali aqueous phase, indicating that the
      hydrolysis of the ester moiety triggered the phase transfer of the AuNPs. We
      found that AuNPs with ester-headed ligands (ester-AuNPs) were internalized into
      HeLa cells at a greater level than were ether-headed AuNPs. 

PMID- 24336512
TI  - Physical exercise habits correlate with gray matter volume of the hippocampus in
      healthy adult humans.
AB  - Physical activity facilitates neurogenesis of dentate cells in the rodent
      hippocampus, a brain region critical for memory formation and spatial
      representation. Recent findings in humans also suggest that aerobic exercise can
      lead to increased hippocampal volume and enhanced cognitive functioning in
      children and elderly adults. However, the association between physical activity
      and hippocampal volume during the period from early adulthood through middle age
      has not been effectively explored. Here, we correlated the number of minutes of
      self-reported exercise per week with gray matter volume of the hippocampus using
      voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of
      age. After controlling for age, gender, and total brain volume, total minutes of
      weekly exercise correlated significantly with volume of the right hippocampus.
      Findings highlight the relationship between regular physical exercise and brain
      structure during early to middle adulthood. 

PMID- 24336514
TI  - Enantioselective Black rearrangement catalyzed by chiral bicyclic imidazole.
AB  - A newly developed chiral imidazole nucleophilic catalyst, , was readily prepared
      and successfully applied to the enantioselective Black rearrangement with up to
      88% ee for a wide range of substrates possessing different substituted groups. A
      plausible mechanism for the high enantioselectivity was proposed. 

PMID- 24336516
TI  - En route to improved phenological models: can space-for-time substitution give
      guidance?

PMID- 24336515
TI  - Condensed tannin biosynthesis and polymerization synergistically condition carbon
      use, defense, sink strength and growth in Populus.
AB  - The partitioning of carbon for growth, storage and constitutive chemical defenses
      is widely framed in terms of a hypothetical sink-source differential that varies
      with nutrient supply. According to this framework, phenolics accrual is passive
      and occurs in source leaves when normal sink growth is not sustainable due to a
      nutrient limitation. In assessing this framework, we present gene and metabolite
      evidence that condensed tannin (CT) accrual is strongest in sink leaves and
      sequesters carbon in a way that impinges upon foliar sink strength and upon
      phenolic glycoside (PG) accrual in Populus. The work was based on two Populus
      fremontii * angustifolia backcross lines with contrasting rates of CT accrual and
      growth, and equally large foliar PG reserves. However, foliar PG accrual was
      developmentally delayed in the high-CT, slow-growth line (SG), and nitrogen
      limitation led to increased foliar PG accrual only in the low-CT, fast-growth
      line (FG). Metabolite profiling of developing leaves indicated comparatively
      carbon-limited amino acid metabolism, depletion of several Krebs cycle
      intermediates and reduced organ sink strength in SG. Gene profiling indicated
      that CT synthesis decreased as leaves expanded and PGs increased. A most striking
      finding was that the nitrogenous monoamine phenylethylamine accumulated only in
      leaves of SG plants. The potential negative impact of CT hyper-accumulation on
      foliar sink strength, as well as a mechanism for phenylethylamine involvement in
      CT polymerization in Populus are discussed. Starch accrual in source leaves and
      CT accrual in sink leaves of SG may both contribute to the maintenance of a slow
      growth phenotype suited to survival in nutrient-poor habitats. 

PMID- 24336517
TI  - Size-dependent changes in leaf and wood chemical traits in two Caribbean
      rainforest trees.
AB  - Tree functional traits and their link to patterns of growth and demography are
      central to informing trait-based analyses of forest communities, and mechanistic
      models of forest dynamics. However, few data are available on how functional
      traits in trees vary through ontogeny, particularly in tropical species; and less
      is known about how patterns of size-dependent changes in traits may differ across
      species of contrasting life-history strategies. Here we describe size-dependent
      variation in seven leaf functional traits and four wood chemical traits, in two
      Dominican rainforest tree species (Dacryodes excelsa Vahl. and Miconia mirabilis
      (Aubl.) L.O. Williams), ranging from small saplings to the largest canopy trees.
      With one exception, all traits showed pronounced variation with tree size
      (diameter at breast height, DBH). Leaf mass per area (LMA), thickness and tissue
      density increased monotonically with DBH in both species. Leaf area, leaf
      nitrogen (N) and carbon (C) : nitrogen (N) ratios also varied significantly with
      DBH; however, these patterns were unimodal, with peak trait values preceding the
      DBH at reproductive onset in both species. Size-dependent changes in leaf
      structural traits (LMA and leaf thickness) were generally similar in both
      species, while traits associated with leaf-level investment in C gain (leaf area,
      leaf C : N ratio) showed contrasting ontogenetic trends between species. Wood
      starch concentration varied with DBH in both species, also showing unimodal
      patterns with peaks preceding size at reproductive onset. Wood C concentration
      increased linearly with DBH in both species, though significantly only in M.
      mirabilis. Size-dependent patterns in wood chemical traits were similar between
      both species. Our data demonstrate pronounced variation in functional traits
      through tree ontogeny, probably due to a combination of environmental factors and
      shifts in resource allocation. Such ontogenetic variation is comparable in
      magnitude with interspecific variation, and so should be accounted for in trait
      based studies of forest dynamics, structure and function. 

PMID- 24336518
TI  - Crystal and local structure refinement in Ca2Al3O6F explored by X-ray diffraction
      and Raman spectroscopy.
AB  - We present a combined structural analysis on the powder of the Ca2Al3O6F phase
      using X-ray diffraction (XRD) and Raman spectroscopy techniques. The crystal
      structure of Ca2Al3O6F has been refined in the rhombohedral system, R3[combining
      macron] space group, a = 17.3237(7) A, c = 7.00017(4) A, V = 1819.38(2) A(3), Z =
      6. The Ca2Al3O6F phase consists of almost ideal AlO4 tetrahedrons linked through
      corners, Ca(2+) ions in voids, and F(-) ions disordered over 6 sites around the
      Ca2 ion. The two different Ca sites have also been verified by the
      photoluminescence spectrum and decay curves using Eu(2+) as the probe ion
      substituted onto the Ca(2+) sites. A lattice dynamics simulation based on the
      simplified version of the Born-Karman potential model has been produced.
      Calculated Raman phonon modes agree qualitatively well with the experimental
      data. The calculations show that the strong line at 538 cm(-1) (Ag) corresponds
      to the vibrational mode of a six-membered AlO4 tetrahedrons ring, and the line at
      572 cm(-1) (Ag) corresponds to the full symmetric vibration of fluorine atoms in
      the ab crystal plane. 

PMID- 24336519
TI  - Quantum state tomography via linear regression estimation.
AB  - A simple yet efficient state reconstruction algorithm of linear regression
      estimation (LRE) is presented for quantum state tomography. In this method,
      quantum state reconstruction is converted into a parameter estimation problem of
      a linear regression model and the least-squares method is employed to estimate
      the unknown parameters. An asymptotic mean squared error (MSE) upper bound for
      all possible states to be estimated is given analytically, which depends
      explicitly upon the involved measurement bases. This analytical MSE upper bound
      can guide one to choose optimal measurement sets. The computational complexity of
      LRE is O(d(4)) where d is the dimension of the quantum state. Numerical examples
      show that LRE is much faster than maximum-likelihood estimation for quantum state
      tomography. 

PMID- 24336520
TI  - Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum
      stress and metabolic defects.
AB  - Endoplasmic reticulum-localized DnaJ 4 (ERdj4) is an immunoglobulin-binding
      protein (BiP) cochaperone and component of the endoplasmic reticulum-associated
      degradation (ERAD) pathway that functions to remove unfolded/misfolded substrates
      from the ER lumen under conditions of ER stress. To elucidate the function of
      ERdj4 in vivo, we disrupted the ERdj4 locus using gene trap (GT) mutagenesis,
      leading to hypomorphic expression of ERdj4 in mice homozygous for the trapped
      allele (ERdj4(GT/GT)). Approximately half of ERdj4(GT/GT) mice died perinatally
      associated with fetal growth restriction, reduced hepatic glycogen stores, and
      hypoglycemia. Surviving adult mice exhibited evidence of constitutive ER stress
      in multiple cells/tissues, including fibroblasts, lung, kidney, salivary gland,
      and pancreas. Elevated ER stress in pancreatic beta cells of ERdj4(GT/GT) mice
      was associated with beta cell loss, hypoinsulinemia, and glucose intolerance.
      Collectively these results suggest an important role for ERdj4 in maintaining ER
      homeostasis during normal fetal growth and postnatal adaptation to metabolic
      stress. 

PMID- 24336523
TI  - Speciation dynamics of metals in dispersion of nanoparticles with discrete
      distribution of charged binding sites.
AB  - We report a comprehensive theory to evaluate the kinetics of complex formation
      between metal ions and charged spherical nanoparticles. The latter consist of an
      ion-impermeable core surrounded by a soft shell layer characterized by a discrete
      axisymmetric 2D distribution of charged sites that bind metal ions. The theory
      explicitly integrates the conductive diffusion of metal ions from bulk solution
      toward the respective locations of the reactive sites within the particle shell
      volume. The kinetic constant k for outer-sphere nanoparticle-metal association is
      obtained from the sum of the contributions stemming from all reactive sites, each
      evaluated from the corresponding incoming flux of metal ions derived from steady
      state Poisson-Nernst-Planck equations. Illustrations are provided to capture the
      basic intertwined impacts of particle size, overall particle charge, spatial
      heterogeneity in site distribution, type of particle (hard, core-shell or porous)
      and concentration of the background electrolyte on k. As a limit, k converges
      with predictions from previously reported analytical expressions derived for
      porous particles with low and high charge density, cases that correspond to
      coulombic and mean-field (smeared-out) electrostatic treatments, respectively.
      The conditions underlying the applicability of these latter approaches are
      rigorously identified in terms of (i) the extent of overlap between electric
      double layers around charged neighbouring sites, and (ii) the magnitude of the
      intraparticulate metal concentration gradient. For the first time, the proposed
      theory integrates the differentiated impact of the local potential around the
      charged binding sites amidst the overall particle field, together with that of
      the so-far discarded intraparticulate flux of metal ions. 

PMID- 24336521
TI  - Soft matrix is a natural stimulator for cellular invasiveness.
AB  - Directional mesenchymal cell invasion in vivo is understood to be a stimulated
      event and to be regulated by cytokines, chemokines, and types of extracellular
      matrix (ECM). Instead, by focusing on the cellular response to ECM stiffness, we
      found that soft ECM (low stiffness) itself is sufficient to prevent stable cell
      to-cell adherens junction formation, up-regulate matrix metalloproteinase (MMP)
      secretion, promote MMP activity, and induce invadosome-like protrusion (ILP)
      formation. Consistently, similar ILP formation was also detected in a three
      dimensional directional invasion assay in soft matrix. Primary human fibroblasts
      spontaneously form ILPs in a very narrow range of ECM stiffness (0.1-0.4 kPa),
      and such ILP formation is Src family kinase dependent. In contrast, spontaneous
      ILP formation in malignant cancer cells and fibrosarcoma cells occurs across a
      much wider range of ECM stiffness, and these tumor cell ILPs are also more
      prominent at lower stiffness. These findings suggest that ECM softness is a
      natural stimulator for cellular invasiveness. 

PMID- 24336522
TI  - Protein kinase D2 induces invasion of pancreatic cancer cells by regulating
      matrix metalloproteinases.
AB  - Pancreatic cancer cell invasion, metastasis, and angiogenesis are major
      challenges for the development of novel therapeutic strategies. Protein kinase D
      (PKD) isoforms are involved in controlling tumor cell motility, angiogenesis, and
      metastasis. In particular PKD2 expression is up-regulated in pancreatic cancer,
      whereas PKD1 expression is lowered. We report that both kinases control
      pancreatic cancer cell invasive properties in an isoform-specific manner. PKD2
      enhances invasion in three-dimensional extracellular matrix (3D-ECM) cultures by
      stimulating expression and secretion of matrix metalloproteinases 7 and 9
      (MMP7/9), by which MMP7 is likely to act upstream of MMP9. Knockdown of MMP7/9
      blocks PKD2-mediated invasion in 3D-ECM assays and in vivo using tumors growing
      on chorioallantois membranes. Furthermore, MMP9 enhances PKD2-mediated tumor
      angiogenesis by releasing extracellular matrix-bound vascular endothelial growth
      factor A, increasing its bioavailability and angiogenesis. Of interest, specific
      knockdown of PKD1 in PKD2-expressing pancreatic cancer cells further enhanced the
      invasive properties in 3D-ECM systems by generating a high-motility phenotype.
      Loss of PKD1 thus may be beneficial for tumor cells to enhance their matrix
      invading abilities. In conclusion, we define for the first time PKD1 and 2
      isoform-selective effects on pancreatic cancer cell invasion and angiogenesis, in
      vitro and in vivo, addressing PKD isoform specificity as a major factor for
      future therapeutic strategies. 

PMID- 24336524
TI  - Clinical biomarkers in metabolic syndrome.
AB  - A biomarker can be defined as a measurable variable that may be used as an
      indicator of a given biological state or condition. Biomarkers have been used in
      health and disease for diagnostic purposes, as tools to assess effectiveness of
      nutritional or drug intervention, or as risk markers to predict the development
      of certain diseases. In nutrition studies, selecting appropriate biomarkers is
      important to assess compliance, or incidence of a particular dietary component in
      the biochemistry of the organism, and in the diagnosis and prognosis of nutrition
      related diseases. Metabolic syndrome is a cluster of cardiovascular risk factors
      that occur simultaneously in the same individual, and it is associated with
      systemic alterations that may involve several organs and tissues. Given its close
      association with obesity and the increasing prevalence of obesity worldwide,
      identifying obese individuals at risk for metabolic syndrome is a major clinical
      priority. Biomarkers for metabolic syndrome are therefore potential important
      tools to maximize the effectiveness of treatment in subjects who would likely
      benefit the most. Choice of biomarkers may be challenging due to the complexity
      of the syndrome, and this article will mainly focus on nutrition biomarkers
      related to the diagnosis and prognosis of the metabolic syndrome. 

PMID- 24336525
TI  - Biomarkers of fish oil omega-3 polyunsaturated fatty acids intake in humans.
AB  - A biomarker is a measured characteristic that may be used as an indicator of some
      biological state or condition. In health and disease, biomarkers have been used
      not only for clinical diagnosis purposes but also as tools to assess
      effectiveness of a nutrition or drug intervention. When considering nutrition
      studies, evaluating the appropriate biomarker is a useful tool to assess
      compliance and incidence of a particular dietary component in the biochemistry of
      the organism. Fish oil is rich in omega-3 fatty acids that have well-known
      beneficial effects on human health mainly through its anti-inflammatory
      properties. It has been widely use to improve health and as a nutrition
      supplement in different pathological conditions such as cardiovascular,
      neurological, and critically ill related diseases. Eicosapentaenoic acid and
      docosahexaenoic acid levels present in different biological moieties (plasma,
      cellular membranes, adipose tissue, etc) are the best biomarkers of fish oil
      intake. Each biological source of fatty acids has its own advantages and
      disadvantages, thus which biomarker to choose and where to measure it requires a
      comprehension of the objectives of the investigation. In this article we will
      review key facts about fish oil intake biomarkers to evaluate how components of a
      specific diet could be monitored and identified in biological samples. Having an
      accurate assessment of nutrition patterns could provide effective targets for
      intervention aimed at modifying eating habits and lifestyle towards the
      improvement of health. 

PMID- 24336526
TI  - Uruguay legalises sale and production of marijuana.

PMID- 24336527
TI  - Should family physicians accept gifts from patients?

PMID- 24336529
TI  - Clinical vignettes to help you deprescribe medications in elderly patients:
      Introduction to the polypharmacy case series.

PMID- 24336530
TI  - Accepting gifts from patients.

PMID- 24336531
TI  - All I want for Christmas is amoxicillin.

PMID- 24336533
TI  - System of therapy.

PMID- 24336534
TI  - Chiropractors respond.

PMID- 24336535
TI  - Misleading title.

PMID- 24336537
TI  - Treatment options for localized prostate cancer.
AB  - OBJECTIVE: To describe treatment options for clinically localized prostate
      cancer: radical prostatectomy, prostate brachytherapy, external beam radiation,
      and active surveillance. QUALITY OF EVIDENCE: Prostate-specific antigen (PSA)
      outcomes presented are from non-randomized, cohort, and other comparisons trials
      (level II evidence). We describe PSA outcomes from Canadian centres when they are
      available. One small randomized controlled trial (level I evidence) in localized
      prostate cancer is available to compare radical prostatectomy with brachytherapy.
      MAIN MESSAGE: Treatment choice in prostate cancer is based on initial PSA level,
      clinical stage of disease, and Gleason score, together with baseline urinary
      function, comorbidities, and patient age. In this article, we describe patients'
      eligibility for and the common side effects of all treatment options. Prostate
      brachytherapy and active surveillance have evolved as new standard treatments of
      localized prostate cancer. We give a brief overview of the brachytherapy
      procedure, side effects, and PSA outcomes across Canada, as well as active
      surveillance guidelines. CONCLUSION: Prostate cancer treatment requires a
      multidisciplinary approach, with input from both urology and radiation oncology.
      Input from family physicians is often as important in helping guide patients
      through the treatment decision process.

PMID- 24336538
TI  - Canadian guidelines for chronic rhinosinusitis: Clinical summary.
AB  - OBJECTIVE: To provide a clinical summary of the Canadian clinical practice
      guidelines for chronic rhinosinusitis (CRS) that includes recommendations
      relevant for family physicians. QUALITY OF EVIDENCE: Guideline authors performed
      a systematic literature search and drafted recommendations. Recommendations
      received both strength of evidence and strength of recommendation ratings. Input
      from external content experts was sought, as was endorsement from Canadian
      medical societies (Association of Medical Microbiology and Infectious Disease
      Canada, Canadian Society of Allergy and Clinical Immunology, Canadian Society of
      Otolaryngology-Head and Neck Surgery, Canadian Association of Emergency
      Physicians, and Family Physicians Airways Group of Canada). MAIN MESSAGE:
      Diagnosis of CRS is based on type and duration of symptoms and an objective
      finding of inflammation of the nasal mucosa or paranasal sinuses. Chronic
      rhinosinusitis is categorized based on presence or absence of nasal polyps, and
      this distinction leads to differences in treatment. Chronic rhinosinusitis with
      nasal polyps is treated with intranasal corticosteroids. Antibiotics are
      recommended when symptoms indicate infection (pain or purulence). For CRS without
      nasal polyps, intranasal corticosteroids and second-line antibiotics (ie,
      amoxicillin- clavulanic acid combinations or fluoroquinolones with enhanced Gram
      positive activity) are recommended. Saline irrigation, oral steroids, and allergy
      testing might be appropriate. Failure of response should prompt consideration of
      alternative diagnoses and referral to an otolaryngologist. Patients undergoing
      endoscopic sinus surgery require postoperative treatment and follow-up.
      CONCLUSION: The Canadian guidelines provide diagnosis and treatment approaches
      based on the current understanding of the disease and available evidence.
      Additionally, the guidelines provide the expert opinion of a diverse group of
      practice and academic experts to help guide clinicians where evidence is sparse.

PMID- 24336539
TI  - From ABCs to GRADE: Canadian Task Force on Preventive Health Care's new rating
      system for clinical practice guidelines.

PMID- 24336540
TI  - Pruritus in pregnancy: treatment of dermatoses unique to pregnancy.
AB  - QUESTION: Some of my pregnant patients complain about pruritus. Are there
      conditions in pregnancy that present with pruritus that might put the mother or
      fetus at risk? ANSWER: Although most cases of pruritus can be attributed to itchy
      dry skin, there are conditions unique to pregnancy that involve pruritus as a
      leading symptom. These include pemphigoid gestationis, pruritic urticarial
      papules and plaques of pregnancy, intrahepatic cholestasis of pregnancy, and
      atopic eruption of pregnancy. These conditions are associated with severe
      pruritus and some might be associated with adverse fetal outcomes. Clinical
      history and physical examination are the most important diagnostic clues when
      evaluating pruritus in pregnancy.

PMID- 24336541
TI  - Laundry detergent capsules and pediatric poisoning.
AB  - QUESTION: A 4-year-old girl was brought into the emergency department vomiting
      after having had ingested a laundry detergent capsule (LDC) from under the sink
      at her house. What is the risk of LDC poisoning? What can be done to treat these
      children? ANSWER: Laundry detergent capsules are relatively new to supermarket
      shelves in North America, and there has been an emergence of case reports in the
      literature describing LDC poisoning, which is worse than poisoning from other
      laundry detergents. Very little is known about the mechanisms causing these
      severe reactions, which include airway compromise and esophageal perforation, but
      the attractive appearance of these capsules and easy access at home has
      governments and health officials concerned about an increase in poisoning. No
      residual problems have been associated with these cases to date; however, further
      research is needed to assess long-term effects.

PMID- 24336542
TI  - Ascites in patients with cirrhosis.

PMID- 24336543
TI  - Reducing fall risk while managing hypotension, pain, and poor sleep in an 83-year
      old woman.

PMID- 24336544
TI  - Is diabetes a coronary artery disease equivalent?

PMID- 24336545
TI  - Question: Can you identify this condition? Acute retinal necrosis.

PMID- 24336546
TI  - Do adventure sports have a role in health promotion? Need for objective evidence
      for a risk-benefit analysis.

PMID- 24336547
TI  - Canadian family doctors' roles and responsibilities toward outbound medical
      tourists: "Our true role is ... within the confines of our system".
AB  - OBJECTIVE: To explore how Canadian family doctors understand their roles and
      responsibilities toward patients who seek health care abroad. DESIGN: Six focus
      groups were held with family doctors across British Columbia to explore their
      experiences with and perspectives on outbound medical tourism. Focus groups were
      digitally recorded, transcribed, and subsequently thematically coded to discover
      common issues and themes across the entire data set. SETTING: Focus groups were
      held with family doctors in 6 cities in British Columbia that provided
      representation from all provincial health authorities and a range of urban
      contexts. PARTICIPANTS: A total of 22 currently practising family doctors
      participated across the 6 focus groups, with groups ranging in size from 2 to 6
      participants (average 4 participants). METHODS: Thematic analysis of the
      transcripts identified cross-cutting themes that emerged across the 6 focus
      groups. MAIN FINDINGS: Participants reported that medical tourism threatened
      patients' continuity of care. Informational continuity is disrupted before
      patients go abroad because patients regularly omit family doctors from
      preoperative planning and upon return home when patients lack complete or
      translated medical reports. Participants believed that their responsibilities to
      patients resumed once the patients had returned home from care abroad, but were
      worried about not being able to provide adequate follow-up care. Participants
      were also concerned about bearing legal liability toward patients should they be
      asked to clinically support treatments started abroad. CONCLUSION: Medical
      tourism poses challenges to Canadian family doctors when trying to reconcile
      their traditional roles and responsibilities with the novel demands of private
      out-of-country care pursued by their patients. Guidance from professional bodies
      regarding physicians' responsibilities to Canadian medical tourists is currently
      lacking. Developing these supports would help address challenges faced in
      clinical practice.

PMID- 24336548
TI  - Anatomy lessons.

PMID- 24336550
TI  - The CFPC announces its 2013-2014 president, Dr Kathy Lawrence.

PMID- 24336553
TI  - Acknowledging excellence and supporting members in meeting community needs.

PMID- 24336559
TI  - ColonCancerCheck primary care invitation pilot project: patient perceptions.
AB  - OBJECTIVE: To describe the perceptions of those who received invitations to the
      ColonCancerCheck Primary Care Invitation Pilot (the Pilot) about the mailed
      invitation, colorectal cancer (CRC) screening in general, and their specific
      screening experiences. DESIGN: Qualitative study with 6 focus group sessions,
      each 1.5 hours in length. SETTING: Hamilton, Ont; Ottawa, Ont; and Thunder Bay,
      Ont. PARTICIPANTS: Screening-eligible adults, aged 50 years and older, who
      received a Pilot invitation for CRC screening. METHODS: The focus groups were
      conducted by a trained moderator and were audiorecorded and transcribed verbatim.
      The transcripts were analyzed using grounded-theory techniques facilitated by the
      use of electronic software. MAIN FINDINGS: Key themes related to the invitation
      letter, the role of the family physician, direct mailing of the fecal occult
      blood testing (FOBT) kit, and alternate CRC screening promotion strategies were
      identified. Specifically, participants suggested the letter content should use
      stronger, more powerful language to capture the reader's attention. The
      importance of the family physician was endorsed, although participants favoured
      clarification of the physician and program roles in the actual mailed invitation.
      Participants expressed support for directly mailing FOBT kits to individuals,
      particularly those with successful previous test completion, and for
      communication of both negative and positive screening results. CONCLUSION: This
      study yielded a number of important findings including strategies to optimize
      letter content, support for directly mailed FOBT kits, and strategies to report
      results that might be highly relevant to other health programs where population
      based CRC screening is being considered.

PMID- 24336560
TI  - Feasibility of a call-in centre to deliver colorectal cancer screening in primary
      care.
AB  - OBJECTIVE: To evaluate the feasibility of a call-in centre to deliver colorectal
      cancer (CRC) screening in primary care through self-administered fecal occult
      blood testing (FOBT). DESIGN: Four-month intervention study (September 2010 to
      January 2011) with randomly selected follow-up interviews. SETTING: The family
      medicine clinics of 3 hospitals in Montreal, Que. PARTICIPANTS: Letters from
      doctors invited their patients to contact the call-in centre (N = 761). Eligible
      patients agreeing to FOBT were sent testing kits that could be returned by mail
      (N = 100). Randomly selected patients (N = 36) were interviewed to explore the
      reasons why they did not contact the call-in centre, or why they did or did not
      adhere to FOBT. MAIN OUTCOME MEASURES: Feasibility was assessed by the
      proportions of patients who contacted the call-in centre, who were eligible for
      FOBT, and who adhered to FOBT; and by the time between invitation mail-out and
      contact with the call-in centre, initial telephone contact and receipt of the
      signed consent form, and FOBT kit mail-out and receipt of the kit by the
      laboratory. Hierarchical logistic regression evaluated the effect of patient
      characteristics on feasibility indicators, adjusting for clustering by physician
      and centre. RESULTS: Of 761 patients (61.6% female, mean age 61.0 years), 250
      (32.9%) contacted the call-in centre, of whom 100 (40.0%) were eligible for and
      consented to FOBT; 62 (62.0%) of these patients adhered to FOBT. Median
      (interquartile range) time from invitation mail-out to call-in centre contact was
      21 (7 to 29) days, from initial telephone contact to receipt of the signed
      consent form was 24 (10 to 38) days, and from FOBT kit mail-out to receipt at the
      laboratory was 23 (18 to 32) days. With the exception of previous cancer
      diagnosis, patient characteristics were not associated with feasibility
      indicators. Of the 115 (46.0%) patients determined to be ineligible for FOBT
      screening, 111 (96.5%) were up to date with or already scheduled for screening.
      CONCLUSION: Feasibility of the call-in centre was demonstrated. Targeting
      screening-eligible individuals or coupling a call-in service with another
      evidence-based CRC screening improvement strategy might further improve uptake of
      fecal testing.

PMID- 24336561
TI  - Colorectal cancer screening practices in Saskatchewan: Survey of family
      physicians.
AB  - OBJECTIVE: To evaluate current colorectal cancer (CRC) screening practices in
      Saskatchewan and identify barriers to screening with the goal of improving
      current practice. DESIGN: Survey of family physicians. SETTING: Saskatchewan.
      PARTICIPANTS: A total of 773 family physicians were surveyed. MAIN OUTCOME
      MEASURES: Demographic characteristics, individual screening practices, and
      perceived barriers to screening. RESULTS: The response rate to the survey was
      44.5%. When asked what method they used for fecal occult blood testing, almost
      40% of respondents were either unsure or did not answer the question. Of those
      who did respond, 35.8% employed hemoccult testing following digital rectal
      examination, a practice not recommended for CRC screening. Screening guidelines
      for average-risk patients were generally well adhered to, with 79.9% of
      respondents recommending screening beginning at age 50. For screening patients at
      increased risk of CRC owing to family history, only 64.2% of respondents began
      screening 10 years before the age of the index patient at diagnosis. Physicians
      who were more likely to follow guidelines were female, in practice fewer than 10
      years, trained in Canada, and practising in urban areas. More than 90% of family
      physicians agreed that a standard provincewide screening program would be
      beneficial. CONCLUSION: We have identified considerable knowledge gaps with
      regard to CRC screening. There is confusion about which fecal occult blood tests
      are recommended for screening. Also, screening guidelines for patients with a
      family history of CRC are poorly understood. These findings suggest that better
      physician education about CRC screening is required. Introduction of a
      provincewide screening program should improve overall screening success.

PMID- 24336562
TI  - Bone mineral density testing after fragility fracture: Informative test results
      likely.
AB  - OBJECTIVE: To determine the proportion of patients with fragility fractures who
      can be expected to have low bone mineral density (BMD) at the time of fracture
      and to assist FPs in deciding whether to refer patients for BMD testing. DATA
      SOURCES: MEDLINE, EMBASE, and CINAHL were searched from the earliest available
      dates through September 2009. STUDY SELECTION: English-language articles
      reporting BMD test results of patients with fragility fractures who were managed
      in an orthopedic environment (eg, fracture clinic, emergency management by
      orthopedic surgeons, inpatients) were eligible for review. While the orthopedic
      environment has been identified as an ideal point for case finding, FPs are often
      responsible for investigation and treatment. Factors that potentially influenced
      BMD test results (eg, selection of fracture types, exclusion criteria) were
      identified. Studies with 2 or more selection factors of potential influence were
      flagged, and rates of low BMD were calculated including and excluding these
      studies. SYNTHESIS: The distribution of the proportion of persons with low BMD
      was summarized across studies using descriptive statistics. We calculated lower
      boundaries on this distribution, using standard statistical thresholds, to
      determine a lower threshold of the expected rate of low BMD. CONCLUSION: Family
      physicians evaluating patients with fragility fractures can expect that at least
      two-thirds of patients with fragility fractures who are older than 50 years of
      age will have low BMD (T score <= -1.0). With this a priori expectation, FPs
      might more readily conduct a fracture risk assessment and pursue warranted
      fracture risk reduction strategies following fragility fracture.

PMID- 24336563
TI  - David Pontin MD CCFP(EM).

PMID- 24336564
TI  - A geological perspective on potential future sea-level rise.
AB  - During ice-age cycles, continental ice volume kept pace with slow, multi
      millennial scale, changes in climate forcing. Today, rapid greenhouse gas (GHG)
      increases have outpaced ice-volume responses, likely committing us to > 9 m of
      long-term sea-level rise (SLR). We portray a context of naturally precedented SLR
      from geological evidence, for comparison with historical observations and future
      projections. This context supports SLR of up to 0.9 (1.8) m by 2100 and 2.7 (5.0)
      m by 2200, relative to 2000, at 68% (95%) probability. Historical SLR
      observations and glaciological assessments track the upper 68% limit. Hence,
      modern change is rapid by past interglacial standards but within the range of
      'normal' processes. The upper 95% limit offers a useful low probability/high risk
      value. Exceedance would require conditions without natural interglacial
      precedents, such as catastrophic ice-sheet collapse, or activation of major East
      Antarctic mass loss at sustained CO2 levels above 1000 ppmv. 

PMID- 24336565
TI  - En route to multicatalysis: kinetic resolution of trans-cycloalkane-1,2-diols via
      oxidative esterification.
AB  - We demonstrate the application of a multicatalyst to the oxidation of a broad
      variety of aldehydes and subsequent enantioselective esterification of the
      incipient acids with (+/-)-trans-cycloalkane-1,2-diols. This reaction operates
      well with a multicatalyst bearing two independent catalytic moieties that provide
      monoprotected 1,2-diols in one pot. 

PMID- 24336567
TI  - Transient water vapor at Europa's south pole.
AB  - In November and December 2012, the Hubble Space Telescope (HST) imaged Europa's
      ultraviolet emissions in the search for vapor plume activity. We report
      statistically significant coincident surpluses of hydrogen Lyman-alpha and oxygen
      OI 130.4-nanometer emissions above the southern hemisphere in December 2012.
      These emissions were persistently found in the same area over the 7 hours of the
      observation, suggesting atmospheric inhomogeneity; they are consistent with two
      200-km-high plumes of water vapor with line-of-sight column densities of about
      10(20) per square meter. Nondetection in November 2012 and in previous HST images
      from 1999 suggests varying plume activity that might depend on changing surface
      stresses based on Europa's orbital phases. The plume was present when Europa was
      near apocenter and was not detected close to its pericenter, in agreement with
      tidal modeling predictions. 

PMID- 24336568
TI  - Ultrafast long-range charge separation in organic semiconductor photovoltaic
      diodes.
AB  - Understanding the charge-separation mechanism in organic photovoltaic cells
      (OPVs) could facilitate optimization of their overall efficiency. Here we report
      the time dependence of the separation of photogenerated electron hole pairs
      across the donor-acceptor heterojunction in OPV model systems. By tracking the
      modulation of the optical absorption due to the electric field generated between
      the charges, we measure ~200 millielectron volts of electrostatic energy arising
      from electron-hole separation within 40 femtoseconds of excitation, corresponding
      to a charge separation distance of at least 4 nanometers. At this separation, the
      residual Coulomb attraction between charges is at or below thermal energies, so
      that electron and hole separate freely. This early time behavior is consistent
      with charge separation through access to delocalized pi-electron states in
      ordered regions of the fullerene acceptor material. 

PMID- 24336569
TI  - Genetic screens in human cells using the CRISPR-Cas9 system.
AB  - The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)
      Cas9 system for genome editing has greatly expanded the toolbox for mammalian
      genetics, enabling the rapid generation of isogenic cell lines and mice with
      modified alleles. Here, we describe a pooled, loss-of-function genetic screening
      approach suitable for both positive and negative selection that uses a genome
      scale lentiviral single-guide RNA (sgRNA) library. sgRNA expression cassettes
      were stably integrated into the genome, which enabled a complex mutant pool to be
      tracked by massively parallel sequencing. We used a library containing 73,000
      sgRNAs to generate knockout collections and performed screens in two human cell
      lines. A screen for resistance to the nucleotide analog 6-thioguanine identified
      all expected members of the DNA mismatch repair pathway, whereas another for the
      DNA topoisomerase II (TOP2A) poison etoposide identified TOP2A, as expected, and
      also cyclin-dependent kinase 6, CDK6. A negative selection screen for essential
      genes identified numerous gene sets corresponding to fundamental processes. Last,
      we show that sgRNA efficiency is associated with specific sequence motifs,
      enabling the prediction of more effective sgRNAs. Collectively, these results
      establish Cas9/sgRNA screens as a powerful tool for systematic genetic analysis
      in mammalian cells. 

PMID- 24336572
TI  - Self-accelerating CO sorption in a soft nanoporous crystal.
AB  - Carbon monoxide (CO) produced in many large-scale industrial oxidation processes
      is difficult to separate from nitrogen (N2), and afterward, CO is further
      oxidized to carbon dioxide. Here, we report a soft nanoporous crystalline
      material that selectively adsorbs CO with adaptable pores, and we present
      crystallographic evidence that CO molecules can coordinate with copper(II) ions.
      The unprecedented high selectivity was achieved by the synergetic effect of the
      local interaction between CO and accessible metal sites and a global
      transformation of the framework. This transformable crystalline material realized
      the separation of CO from mixtures with N2, a gas that is the most competitive to
      CO. The dynamic and efficient molecular trapping and releasing system is
      reminiscent of sophisticated biological systems such as heme proteins. 

PMID- 24336571
TI  - Genome-scale CRISPR-Cas9 knockout screening in human cells.
AB  - The simplicity of programming the CRISPR (clustered regularly interspaced short
      palindromic repeats)-associated nuclease Cas9 to modify specific genomic loci
      suggests a new way to interrogate gene function on a genome-wide scale. We show
      that lentiviral delivery of a genome-scale CRISPR-Cas9 knockout (GeCKO) library
      targeting 18,080 genes with 64,751 unique guide sequences enables both negative
      and positive selection screening in human cells. First, we used the GeCKO library
      to identify genes essential for cell viability in cancer and pluripotent stem
      cells. Next, in a melanoma model, we screened for genes whose loss is involved in
      resistance to vemurafenib, a therapeutic RAF inhibitor. Our highest-ranking
      candidates include previously validated genes NF1 and MED12, as well as novel
      hits NF2, CUL3, TADA2B, and TADA1. We observe a high level of consistency between
      independent guide RNAs targeting the same gene and a high rate of hit
      confirmation, demonstrating the promise of genome-scale screening with Cas9. 

PMID- 24336570
TI  - Mutational analysis reveals the origin and therapy-driven evolution of recurrent
      glioma.
AB  - Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent
      disease may fail, at least in part, because the genomic alterations driving the
      growth of recurrences are distinct from those in the initial tumor. To explore
      this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and
      recurrent tumors resected from the same patients. In 43% of cases, at least half
      of the mutations in the initial tumor were undetected at recurrence, including
      driver mutations in TP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent
      tumors are often seeded by cells derived from the initial tumor at a very early
      stage of their evolution. Notably, tumors from 6 of 10 patients treated with the
      chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary
      path to high-grade glioma. At recurrence, these tumors were hypermutated and
      harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian
      target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.

PMID- 24336573
TI  - Discovery of 505-million-year old chitin in the basal demosponge Vauxia
      gracilenta.
AB  - Sponges are probably the earliest branching animals, and their fossil record
      dates back to the Precambrian. Identifying their skeletal structure and
      composition is thus a crucial step in improving our understanding of the early
      evolution of metazoans. Here, we present the discovery of 505-million-year-old
      chitin, found in exceptionally well preserved Vauxia gracilenta sponges from the
      Middle Cambrian Burgess Shale. Our new findings indicate that, given the right
      fossilization conditions, chitin is stable for much longer than previously
      suspected. The preservation of chitin in these fossils opens new avenues for
      research into other ancient fossil groups. 

PMID- 24336574
TI  - Domain structure for an amorphous iridium-oxide water-oxidation catalyst
      characterized by X-ray pair distribution function analysis.
AB  - The domain structure of an amorphous, "blue layer" iridium-oxide water-oxidation
      catalyst film (BL) electrodeposited from the soluble precursor complex,
      [Cp*Ir(H2O)3]SO4, was characterized by X-ray pair distribution function (PDF)
      analysis. The results show that the experimental PDF can be fit remarkably well
      using a single Ir5O22 cluster extracted from the rutile lattice. The model
      includes distortions that indicate the presence of Ir(MU-O)3Ir or distorted Ir(MU
      O)2Ir substructures, and hence deviations from a rutile structure. The five Ir
      atom cluster is suggested to represent the population-averaged distribution of
      metal-oxo clusters in the film. BL is found to be distinguished from other
      amorphous film water-oxidation catalysts because of the remarkably small domain
      size and homogeneity. As such, the blue layer catalyst provides a model for
      investigating ligand-determined metal-oxide cluster assembly and catalyst
      mechanism. 

PMID- 24336576
TI  - Errors in after-hours phone consultations: a simulation study.
AB  - BACKGROUND: After-hours out-of-hospital phone consultations require physicians to
      make decisions based on information provided by a nurse over the phone. METHODS:
      We conducted a simulation study to evaluate physicians' actions following
      communication of key information. 22 nurses were asked to call physicians with
      six cases based on the six most common reasons for after-hours phone calls. We
      evaluated physicians' actions following the communication of key clinical
      information: A situation cue described a patient's problem (eg, confusion). A
      background cue described a specific clinical finding regarding the cause of the
      problem (eg, patient's sodium is low). For each cue we defined a list of
      indicators, based on the medical literature, to ascertain whether physicians
      acted upon the provided information (which was defined as addressing at least one
      of the indicators). RESULTS: A total of 108 phone consultations (containing 88
      situation and 93 background cues) were analysed. Situation cues were communicated
      in 90% (79/88) of the calls and background cues in 33% (31/93). Physician acted
      upon the provided information in 57% (45/79) and 48% (15/31) of the communicated
      situation and background cues, respectively. When the background cues were not
      communicated, physicians asked questions expected to elicit the cue in 12% of the
      cases. Responding to the situation cue was associated with longer conversations
      and active inquiry by the physician. CONCLUSIONS: After-hours phone calls are
      error prone. Both nurse communication and physician decision-making are
      problematic. Efforts to improve patient safety in this setting must address both
      communication and decision-making.

PMID- 24336577
TI  - Interactive questioning in critical care during handovers: a transcript analysis
      of communication behaviours by physicians, nurses and nurse practitioners.
AB  - OBJECTIVE: Although there is a growing recognition of the importance of active
      communication behaviours from the incoming clinician receiving a patient
      handover, there are currently no agreed-upon measures to objectively describe
      those behaviours. This study sought to identify differences in incoming clinician
      communication behaviours across levels of clinical training for physicians and
      nurses. METHODS: Handover observations were conducted during shift changes for
      attending physicians, resident physicians, registered nurses and nurse
      practitioners in three medical intensive care units from July 2011 to August
      2012. Measures were the number of interjections from the incoming clinician and
      the communication mode of those interjections. Each collaborative cross-check, a
      specific type of interactive question, was subsequently classified by level of
      assertiveness. RESULTS: 133 patient handovers were analysed. Statistical
      differences were found in both measures. Higher levels of training were
      associated with fewer interjections, and a higher proportion of interactive
      questioning to detect erroneous assessments and actions by the incoming provider.
      All groups were observed to use the least assertive level of a collaborative
      cross-check, which contributed to misunderstandings. Nurses used less assertive
      collaborative cross-checks than physicians. CONCLUSIONS: Differences across
      clinician type and levels of clinical training were found in both measures during
      patient handovers. The findings suggest that training could enable physicians and
      nurses to learn communication competencies during patient handovers which were
      used more frequently by more experienced practitioners, including interjecting
      less frequently and using interactive questioning strategies to clarify
      understanding, and assertively question the appropriateness of diagnoses,
      treatment plans and prognoses. Accompanying cultural change initiatives might be
      required to routinely employ these strategies in the clinical setting,
      particularly for nursing personnel.

PMID- 24336575
TI  - Promoting engagement by patients and families to reduce adverse events in acute
      care settings: a systematic review.
AB  - INTRODUCTION: Patient-centeredness is central to healthcare. Hospitals should
      address patients' unique needs to improve safety and quality. Patient engagement
      in healthcare, which may help prevent adverse events, can be approached as an
      independent patient safety practice (PSP) or as part of a multifactorial PSP.
      OBJECTIVES: This review examines how interventions encouraging this engagement
      have been implemented in controlled trials. METHODS: We searched Medline, CINAHL,
      Embase and Cochrane from 2000 to 2012 for English language studies in hospital
      settings with prospective controlled designs, addressing the effectiveness or
      implementation of patient/family engagement in PSPs. We separately reviewed
      interventions implemented as part of selected broader PSPs by way of example:
      hand hygiene, ventilator-associated pneumonia, rapid response systems and care
      transitions. RESULTS: Six articles met the inclusion criteria for effectiveness
      with a primary focus on patient engagement. We identified 12 studies implementing
      patient engagement as an aspect of selected broader PSPs. A number of studies
      relied on patients' possible function as a reporter of error to healthcare
      workers and patients as a source of reminders regarding safety behaviours, while
      others relied on direct activation of patients or families. Definitions of
      patient and family engagement were lacking, as well as evidence regarding the
      types of patients who might feel comfortable engaging with providers, and in what
      contexts. CONCLUSIONS: While patient engagement in safety is appealing, there is
      insufficient high-quality evidence informing real-world implementation. Further
      work should evaluate the effectiveness of interventions on patient and family
      engagement and clarify the added benefit of incorporating engagement in
      multifaceted approaches to improve patient safety endpoints. In addition,
      strategies to assess and overcome barriers to patients' willingness to actively
      engage in their care should be investigated.

PMID- 24336578
TI  - Nodular kidney involvement in a patient with idiopathic Sweet's syndrome.
AB  - A 40-year-old previously healthy woman presented with a history of painful
      maculopapular rash, fever and diffuse arthralgia. The skin biopsy was consistent
      with Sweet's syndrome. Further workup with abdominal CT revealed bilateral
      hypoenhancing renal lesions involving the cortex and medulla, as well as terminal
      ileal thickening. Her renal function was preserved. The urinalysis revealed
      microscopic haematuria and sterile pyuria. Upper and lower gastrointestinal
      endoscopies were unremarkable and terminal ileal biopsy was normal. The
      evaluation for secondary causes of Sweet's syndrome was negative. She responded
      to corticosteroid therapy. A repeat abdominal CT scan two months later showed
      complete resolution of renal and ileal lesions. One year after the initial
      presentation the patient is doing well with no recurrent symptoms. We concluded
      that the abnormal renal findings were most likely due to sterile abscesses in the
      course of idiopathic Sweet's syndrome. 

PMID- 24336579
TI  - Delayed diagnosis of familial adenomatous polyposis in an adolescent patient with
      a coexisting eating disorder.
AB  - Colorectal carcinoma in the population aged less than 20 years of age is rare but
      associated with poor prognosis, which is attributable to advanced disease at
      presentation and higher incidence of the unfavourable mucinous histology.
      Colorectal carcinoma commonly presents with non-specific gastrointestinal
      symptoms in conjunction with iron deficiency anaemia. Many of these symptoms can
      mimic eating disorders, which are common in adolescent women. We present the case
      of a 20-year-old woman with previously undiagnosed familial adenomatous polyposis
      and colorectal carcinoma who experienced a significant delay in diagnosis, given
      a coexisting eating disorder mimicking her symptoms. After confirmation of the
      diagnosis by colonoscopy and genetic testing, the patient underwent a successful
      proctocolectomy and experienced full recovery. This case is a reminder that
      underlying organic pathology should always be excluded prior to a diagnosis of an
      eating disorder. 

PMID- 24336580
TI  - Lancing of a boil leading to severe invasive methicillin-sensitive Staphylococcus
      aureus infection in an adolescent.
AB  - A 10-year-old boy presented to the emergency department with chief symptoms of
      fever and right leg pain for 3 days. Also of note, he reported that he had a boil
      on his neck 2 weeks prior to admission. This lesion was lanced by his mother with
      a hot needle. An X-ray, CT scan and MRI of the right knee showed no evidence of
      osteomyelitis. He was placed on intravenous vancomycin for empiric treatment.
      Blood culture grew methicillin-susceptible Staphylococcus aureus (MSSA),
      susceptible to vancomycin and clindamycin. He continued to spike fever with the
      development of erythema, and swelling of the distal thigh. Repeat MRI of the
      right knee showed osteomyelitis and subperiosteal abscess in the distal femur
      shaft with surrounding intramuscular abscesses and pyomyositis. He was taken to
      the operating room where 50 mL of fluid was drained from the periosteal abscess
      and a bone biopsy was obtained. Bone marrow culture also grew MSSA, susceptible
      to clindamycin. 

PMID- 24336581
TI  - Acute focal myositis causing significant radiological and histological
      abnormality settles spontaneously with expectant management.
AB  - We discuss two cases of reactive focal myositis that had different clinical
      presentations but responded well to conservative management. These cases
      demonstrate that reactive myositis can present acutely but resolves quickly with
      expectant treatment and has a favourable prognosis. 

PMID- 24336582
TI  - Painful subungual glomus tumour of the left thumb.

PMID- 24336583
TI  - An anchoring technique by looping with the tip of a super-stiff wire: may be a
      solution in patients with anomaly of the aortic arch and tortuous carotid artery
      disease?
AB  - Vascular anatomy is one of the most important factors for the successful carotid
      artery interventions, either angioplasty or stenting. We report a new technique
      for advancing a guiding catheter into the common carotid artery when there is an
      unfavourable aortic arch anatomy and tortuosity of the carotid artery. 

PMID- 24336584
TI  - Marfan syndrome.
AB  - Marfan syndrome is a rare autosomal dominant disorder of the connective tissue,
      with skeletal, ligamentous, orooculofacial, pulmonary, abdominal, neurological
      and the most fatal, cardiovascular manifestations. It has no cure but early
      diagnosis, regular monitoring and preventive lifestyle regimen ensure a good
      prognosis. However, the diagnosis can be difficult as it is essentially a
      clinical one, relying on family history, meticulous physical examination and
      investigation of involved organ systems. Patients of Marfan syndrome portray very
      typical physical and orofacial characteristics, suggesting obvious recognition,
      but due to variable phenotypic expression, cases often go unnoticed unless a full
      range of attributing features is apparent. Dental practitioners are very likely
      to encounter patients of Marfan syndrome at an early age as they frequently
      present for dental treatment. The present case report illustrates the preliminary
      screening of Marfan syndrome in a dental office followed by timely diagnosis and
      appropriate referrals. 

PMID- 24336585
TI  - Innocent left ventricular outflow tract membrane masquerading as vegetation.
AB  - Innocent left ventricular outflow tract (LVOT) membranes are a rare entity and
      found incidentally on echocardiography. The authors report a case of innocent
      LVOT membrane in a patient who was admitted with ischaemic stroke. Initial
      transthoracic echocardiography showed a possible valvular vegetation which was
      thought to be the cause of embolic stroke. Anticoagulation with coumadin and
      antibiotics were started. Subsequent Transesophageal echocardiography showed that
      it was more consistent with innocent LVOT membrane and not vegetation.
      Anticoagulation and antibiotics were discontinued, and on a follow-up over 5
      years later, the membrane was stable in size and location without any
      complications. 

PMID- 24336586
TI  - Using the Valeo dilatable stent in coarctation stenting for small children:
      expanding the inclusion criteria for coarctation stenting?
AB  - The application of coarctation stenting has grown in paediatric and adult
      practice in recent years. Stent and delivery sheath technology has improved;
      however, we remain technically limited when implanting small calibre stents
      through small sheaths in small children, which then have the potential to be
      dilated to adult size as time passes. We describe the first reported use of the
      Valeo Biliary Pre-mounted Re-dilatable Stent (Edwards Life Sciences, California,
      USA) in aortic coarctation with 1 year follow-up including cross-sectional
      imaging. This 14 kg 3-year-old girl presented following an intracerebral
      haemorrhage secondary to severe systemic hypertension. Despite implantation
      through a 7-French sheath, this stent can be postdilated up to 20 mm, and
      therefore provides an important new addition to the interventional armamentarium.

PMID- 24336587
TI  - Treacher Collins syndrome with microcornea and retinal detachment.

PMID- 24336588
TI  - Cirsoid aneurysm of scalp: demonstration on CT angiography (CTA).

PMID- 24336589
TI  - Humeral shaft hypertrophic non-union mimicking malignant lesion.

PMID- 24336591
TI  - Charge-modulated self-assembly and growth of conjugated polyelectrolyte
      polyoxometalate hybrid networks.
AB  - Self-assembly of an anionic polyoxometalate with cationic conjugated
      polyelectrolytes leads to hybrid supramolecular networks whose dimensionality is
      controlled by the chain length and steric charge distribution. 

PMID- 24336590
TI  - Infrared laser pulse triggers increased singlet oxygen production in tumour
      cells.
AB  - Photodynamic therapy (PDT) is a technique developed to treat the ever-increasing
      global incidence of cancer. This technique utilises singlet oxygen ((1)O2)
      generation via a laser excited photosensitiser (PS) to kill cancer cells.
      However, prolonged sensitivity to intensive light (6-8 weeks for lung cancer),
      relatively low tissue penetration by activating light (630 nm up to 4 mm), and
      the cost of PS administration can limit progressive PDT applications. The
      development of quantum-dot laser diodes emitting in the highest absorption region
      (1268 nm) of triplet oxygen ((3)O2) presents the possibility of inducing
      apoptosis in tumour cells through direct (3)O2 -> (1)O2 transition. Here we
      demonstrate that a single laser pulse triggers dose-dependent (1)O2 generation in
      both normal keratinocytes and tumour cells and show that tumour cells yield the
      highest (1)O2 far beyond the initial laser pulse exposure. Our modelling and
      experimental results support the development of direct infrared (IR) laser
      induced tumour treatment as a promising approach in tumour PDT. 

PMID- 24336592
TI  - The interaction of beryllium with benzene and graphene: a comparative
      investigation based on DFT, MP2, CCSD(T), CAS-SCF and CAS-PT2.
AB  - The interaction of beryllium with benzene, graphene and graphitic compounds
      involves multi-reference electronic states, Jahn-Teller distortion, charge
      transfer and van der Waals interactions. This is investigated herein using
      periodic and molecular models at different levels of theory: (i) the second-order
      Moller-Plesset (MP2) perturbation theory, (ii) the coupled cluster method with
      inclusion of single double and perturbative triple excitations (CCSD(T)), (iii)
      the complete active space self-consistent field (CAS-SCF) and (iv) the complete
      active space with perturbation theory truncated at the 2nd order (CAS-PT2).
      Molecular and periodic Density Functional Theory (DFT) methods are also used. The
      two major failures of DFT are addressed with regard to the beryllium benzene and
      graphene interaction: the degeneracy problem is the source of no specific problem
      while the delocalization error causes DFT with the Perdew Burke, Ernzerhof
      functional plus the Grimme correction (DFT/PBE-D2) to be over-binding by about
      0.4 eV at a short-range. The agreement between DFT/PBE-D2 and wave-function based
      methods is nevertheless good; DFT/PBE-D2 provides an accurate description of the
      electronic structure of the system. By the end of this work, we shall get a
      better insight into the mechanisms leading beryllium to physisorb on graphene and
      to chemisorb into the bilayer of graphite. 

PMID- 24336593
TI  - Wet-spinning of PEDOT:PSS/functionalized-SWNTs composite: a facile route toward
      production of strong and highly conducting multifunctional fibers.
AB  - With the aim of fabricating multifunctional fibers with enhanced mechanical
      properties, electrical conductivity and electrochemical performance, we develop
      wet-spinning of composite formulation based on functionalized PEG-SWNT and
      PEDOT:PSS. The method of addition and loading are directly correlated to the
      quality and the ease of spinnability of the formulation and to the mechanical and
      electrical properties of the resultant fibers. Both the fiber modulus (Y) and
      strength (sigma) scaled linearly with PEG-SWNT volume fraction (Vf). A remarkable
      reinforcement rate of dY/dVf = 417 GPa and dsigma/dVf = 4 GPa were obtained when
      PEG-SWNTs at Vf <= 0.02. Further increase of PEG-SWNTs loading (i.e. up to Vf
      0.12) resulted in further enhancements up to 22.8 GPa and 254 MPa in Modulus and
      ultimate stress, respectively. We also show the enhancement of electrochemical
      supercapacitor performance of composite fibers. These outstanding mechanical,
      electrical and electrochemical performances place these fibers among the best
      performing multifunctional composite fibers. 

PMID- 24336594
TI  - [The TERISA study].

PMID- 24336595
TI  - [The PRATO-ACS study].

PMID- 24336596
TI  - [Biomarkers in heart failure: an update].
AB  - Heart failure (HF) represents the final common pathway of cardiovascular
      diseases. Prognosis of HF remains dismal despite a better understanding of its
      pathophysiology and advances in diagnostics and therapeutics. HF is a complex
      syndrome, with an extensive influence on vital organ perfusion and function
      resulting from hemodynamic alterations and with marked arrhythmogenicity,
      following the development of structural abnormalities and adrenergic activation.
      Therefore, current clinical and instrumental approach to the HF syndrome should
      be complemented by novel decision-making strategies, with potential in early
      diagnosis as well as in prognostication and therapeutic definition. In this view,
      there is growing experimental and clinical interest in the use of biomarkers,
      namely B-type natriuretic peptides, whose role in diagnosis, risk stratification
      and patients' follow-up is well recognized. A new targeted approach is envisaged
      in the next future for the management of the heterogeneous clinical phenotype of
      HF, likely based on biomarker tracking specific pathophysiologic pathways of
      disease progression. 

PMID- 24336597
TI  - [Acute myocardial infarction with angiographically normal coronary arteries: what
      are we missing?].
AB  - Myocardial infarction with normal coronary arteries (MINCA) can be observed in a
      relevant subset of patients with MI. It can be considered a syndrome, since it
      includes several clinical entities with specific pathogenetic mechanisms. Its
      prevalence is extremely variable, accounting for 5-25% of all acute myocardial
      infarctions. MINCA may arise from epicardial, microvascular, or myocardial
      localizations. Clinical history, echocardiography, coronary angiography and left
      ventriculography represent the first diagnostic step; however, additional tests
      are often required to confirm the diagnosis. The prognosis is extremely variable,
      depending on the causes of MINCA. Therefore, the identification of the correct
      etiology of MINCA is crucial to stratify patients appropriately and, hence,
      select the best treatment approach. In this review article, the pathogenesis,
      diagnosis, prognosis and therapy of MINCA are discussed, highlighting that
      coronary angiography alone is not sufficient for the complete understanding of
      the pathogenic mechanisms. 

PMID- 24336598
TI  - [Echocardiographic diagnosis of acute aortic syndrome in the emergency
      department].
AB  - An 82-year-old woman was admitted to our emergency department in hemodynamically
      stable condition, 12h after the beginning of severe retrosternal chest pain of 1h
      duration, not influenced by changes in body position, nor aggravated by breathing
      and no more repeated. The ECG showed a typical pattern of acute pericarditis with
      diffuse concave upward ST-segment elevation >1 mm. Cardiac troponin levels, 12h
      after chest pain, were in the normal range, excluding the diagnosis of acute
      coronary syndrome. Chest X-ray displayed significant mediastinal enlargement.
      Transthoracic echocardiography documented mild anterior pericardial effusion (10
      mm) and severe aneurysmal dilatation of the ascending aorta (antero-posterior
      diameter of 7 cm, measured 5 cm above the aortic valve plane) with significant
      wall thickening and no evidence of intimal flap. In addition, both left and right
      ventricles showed normal morphology and systolic function; pulmonary artery
      systolic pressure was 28 mmHg. Transesophageal echocardiography confirmed the
      significant dilatation of the ascending aorta, with a typical pattern of aortic
      penetrating ulcer (observed 5 cm above the aortic valve plane) associated with an
      intramural hematoma of the anterior wall, extended from the level of the sino
      tubular junction to 9 cm above the aortic valve plane (acute aortic syndrome,
      Svensson type II). A diagnosis of acute aortic syndrome was made and, considering
      the risk for acute aortic dissection or aortic rupture, the patient was quickly
      transferred to the nearest Cardiac Surgery Center. Computed tomography confirmed
      the echocardiographic findings and the patient underwent replacement of the
      ascending aorta with a tubular prosthesis. The present case underlines the great
      utility of portable echocardiography in the emergency department, for the
      clinical evaluation of patients with different patterns of chest pain and,
      particularly, in the differential diagnosis of acute aortic syndromes. 

PMID- 24336599
TI  - [Right ventricular mural endocarditis: description of a case].
AB  - We report the case of a 45-year-old man addicted to intravenous drug abuse who
      was admitted to our hospital for dyspnea, fever and chest pain. Chest X-ray
      showed diffuse right lung opacity and pleural effusion. Transthoracic
      echocardiography and contrast-enhanced cardiac magnetic resonance imaging
      revealed a plurilobated, highly mobile mass in the right ventricle originating
      from the moderator band near the apical trabeculae. Cardiac structure and valves
      were normal. Blood cultures were positive for Staphylococcus hominis. The
      diagnosis of infective endocarditis with mural vegetation was made. Specific
      antibiotic therapy was started with success and after 3 weeks the mass
      disappeared. Infective endocarditis with mural vegetation in the absence of
      valvular lesions is uncommon. Differential diagnosis is always required, but
      clinical course should be our guide in decision making. 

PMID- 24336600
TI  - [Role of bioresorbable scaffold and optical coherence tomography in the treatment
      of recurrent in-stent restenosis: a case report].

PMID- 24336602
TI  - [Information and Communication Technology in medicine in Italy: problems and
      perspectives. A document by the "e-cardio" area of the Italian Association of
      Hospital Cardiologists (ANMCO)].
AB  - In Italy, health protection is an individual right protected by the article 32 of
      the Constitution, granted to everyone since 1978 by the foundation of the
      National Health Service. However, regionalization of the healthcare system has
      caused noticeable discrepancies among the different areas of the country. The use
      of the Information and Communication Technology (ICT) may be useful to solve
      them. The purpose of this document is to analyze the implementation of ICT in
      Italy, on the basis of the suggestions given by the Italian Association of
      Hospital Cardiologists (ANMCO). In 2010, the Italian government introduced the
      electronic health record (EHR), which includes a minimum core of essential
      documents that should be created and updated by general practitioners. The
      obvious limitations of this methodology become clear in the urgency-emergency
      clinical setting, where the availability of particular clinical data may
      influence both patient prognosis and cost reduction. Also the privacy rules,
      currently very restrictive, cause a drawback in reliability of the data reported
      in the EHR, thus arising the need for a balance shift from privacy to health
      rights at the level of both the individual and the community. A minimum core of
      mandatory clinical data to be included in the EHR should be defined. No formal
      indications for filling out the medical records are available and most few
      experiences concern "bureaucratic documents" on the diagnostic and therapeutic
      process. Conversely, we believe that medical records should become a diagnostic
      and therapeutic tool that makes health rights uniform across the country. Each
      medical record form should include the following features: a simple interface, a
      mandatory association of clinical findings and reports, data portability and
      accessibility, and adherence of the information to a minimal dataset.
      Additionally, medical records data should merge into a modified EHR available at
      any time and place through network access points with adequate connection speed.
      In this respect, inhomogeneous availability of broadband in Italy is at present a
      major challenging issue. Finally, current training programs in medicine do not
      allow for widespread application of ICT among young physicians. Some essential
      topics should be covered by university formative credits. It is crucial to
      address different needs: the patient needs, making data on "biological heritage"
      always available; the physician needs, providing them with professional tools
      able to improve their daily quality of work; the managers' and public decision
      makers' needs, helping to optimize costs of the healthcare system. 

PMID- 24336601
TI  - [ANMCO/SICI-GISE document on antiplatelet therapy in patients with acute coronary
      syndrome].
AB  - Antiplatelet therapy is the cornerstone of the pharmacologic management of
      patients with acute coronary syndrome (ACS). Over the last years, several studies
      have evaluated old and new oral or intravenous antiplatelet agents in ACS
      patients. In particular, research was focused on assessing superiority of two
      novel platelet ADP P2Y12 receptor antagonists (i.e., prasugrel and ticagrelor)
      over clopidogrel. Several large randomized controlled trials have been undertaken
      in this setting and a wide variety of prespecified and post-hoc analyses are
      available that evaluated the potential benefits of novel antiplatelet therapies
      in different subsets of patients with ACS. The aim of this document is to review
      recent data on the use of current antiplatelet agents for in-hospital treatment
      of ACS patients. For each drug or class of drugs, strong evidence and/or areas of
      uncertainty that warrant further research are highlighted by examining 10
      subgroups of patients with ACS. 

PMID- 24336604
TI  - Organic cage compounds--from shape-persistency to function.
AB  - Defined cavities are found in biological systems, such as in enzymes to
      accelerate specific reactions with specific molecular targets, or as transport
      containers for molecular cargoes. Chemists have been inspired by those phenomena
      found in nature and synthesized defined cage compounds for different purposes,
      such as for stabilizing reactive intermediates, running reactions within the
      cavities or studying recognition events. However, most cage compounds are based
      on the coordination of metal ions, and only a few are charge neutral. Purely
      organic cages are usually charge neutral and more stable due to existing covalent
      bonds. Covalent bonds can be made in two ways, applying irreversible reactions or
      reversible reactions. By introducing dynamic covalent chemistry (DCC), cages have
      become accessible in good yields from rather simple precursors. Here, we compare
      both methods and highlight those that give very good yields. Furthermore, the use
      of organic cage compounds in sorption, recognition, sensing, separation and
      stabilization of molecules will be discussed.

PMID- 24336605
TI  - Fe2O3 nanocrystals anchored onto graphene nanosheets as the anode material for
      low-cost sodium-ion batteries.
AB  - Fe2O3 nanocrystals were uniformly anchored onto graphene nanosheets (Fe2O3@GNS)
      by a nanocasting technique, and the resulting composites were applied as anodes
      of sodium-ion batteries. Fe2O3@GNS exhibits excellent cycling performance and
      rate capability. 

PMID- 24336606
TI  - Spatio-temporal dynamics of automatic processing of phonological information in
      visual words.
AB  - Sensory-specific cortices appear to be sensitive to information from another
      modality. Here we investigate whether the human brain automatically extracts the
      phonological information in visual words in early visual processing. We
      continuously presented native Chinese speakers peripherally with Chinese
      homophone characters in an oddball paradigm, while they performed a visual
      detection task presented in the centre of the visual field. We found the lexical
      tone phonology embedded in the characters is processed automatically by the brain
      of native speakers, as revealed by whole-head electrical recordings of the
      mismatch negativity (MMN). Source solution further revealed the MMN involved the
      neural activations from the visual cortex to the auditory cortex (130-460 ms).
      The spatial-temporal dynamics indicate a visual-auditory interaction in the
      early, automatic processing of phonological information in visual words. 

PMID- 24336607
TI  - Sofosbuvir with ribavirin is safe and effective in hepatitis C genotype 1 with
      unfavourable pretreatment characteristics.

PMID- 24336608
TI  - Statins do not improve cardiovascular outcomes for dialysis patients.

PMID- 24336609
TI  - Raised blood glucose as a predictor of dementia risk in adults with and without
      diabetes.

PMID- 24336611
TI  - The impacts of water stress on phloem transport in Douglas-fir trees.
AB  - Despite the critical role that phloem plays in a number of plant functional
      processes and the potential impact of water stress on phloem structural and
      phloem sap compositional characteristics, little research has been done to
      examine how water stress influences phloem transport. The objectives of this
      study were to develop a more accurate understanding of how water stress affects
      phloem transport in trees, both in terms of the short-term impacts of water
      stress on phloem sap composition and the longer-term impacts on sieve cell
      anatomical characteristics. Phloem sieve cell conductivity (kp) was evaluated
      along a gradient of tree height and xylem water potential in Douglas-fir
      (Pseudotsuga menziesii (Mirb.) Franco) trees in order to evaluate the influence
      of water stress on phloem transport capacity. The Hagen-Poiseuille equation was
      used with measurements of sieve cell anatomical characteristics, water content of
      phloem sap, non-structural carbohydrate content of phloem sap and shoot water
      potential (Psil) to evaluate impacts of water stress on kp. Based on regression
      analysis, for each 1 MPa decrease in mean midday Psil, sieve cell lumen radius
      decreased by 2.63 um MPa(-1). Although there was no significant trend in sucrose
      content with decreasing Psil, glucose and fructose content increased
      significantly with water stress and sieve cell relative water content decreased
      by 13.5% MPa(-1), leading to a significant increase in sugar molar concentration
      of 0.46 mol l(-1) MPa(-1) and a significant increase in viscosity of 0.27 mPa s
      MPa(-1). Modeled kp was significantly influenced both by trends in viscosity as
      well as by water stress-related trends in sieve cell anatomy. 

PMID- 24336612
TI  - Photoprotection of evergreen and drought-deciduous tree leaves to overcome the
      dry season in monsoonal tropical dry forests in Thailand.
AB  - In tropical dry forests, uppermost-canopy leaves of evergreen trees possess the
      ability to use water more conservatively compared with drought-deciduous trees,
      which may result from significant differences in the photoprotective mechanisms
      between functional types. We examined the seasonal variations in leaf gas
      exchange, chlorophyll fluorescence and the amounts of photosynthetic pigments
      within lamina of the uppermost-canopy leaves of three drought-deciduous trees
      (Vitex peduncularis Wall., Xylia xylocarpa (Roxb.) W. Theob., Shorea siamensis
      Miq.), a semi-deciduous tree (Irvingia malayana Miq.) and two evergreen trees
      (Hopea ferrea Lanessan and Syzygium cumini (L.) Skeels) in Thailand. Area-based
      maximum carbon assimilation rates (Amax) decreased during the dry season, except
      in S. siamensis. The electron transport rate (ETR) remained unchanged in
      deciduous trees, but decreased during the dry season in evergreen and semi
      deciduous trees. In the principal component analysis, the first axis (Axis 1)
      accounted for 44.3% of the total variation and distinguished deciduous from
      evergreen trees. Along Axis 1, evergreen trees were characterized by a high Stern
      Volmer non-photochemical quenching coefficient (NPQ), high xanthophyll cycle
      pigments/chlorophyll and a high de-epoxidation state of the xanthophyll cycle,
      whereas the deciduous trees were characterized by a high ETR, a high quantum
      yield of PSII (PhiPSII = (Fm(') -F)/Fm(')) and a high mass-based Amax under high
      light conditions. These findings indicate that drought-deciduous trees showing
      less conservative water use tend to dissipate a large proportion of electron flow
      through photosynthesis or alternative pathways. In contrast, the evergreens
      showed more conservative water use, reduced Amax and ETR and enhanced NPQ and
      xanthophyll cycle pigments/chlorophyll during the dry season, indicating that
      down-regulated photosynthesis with enhanced thermal dissipation of excess light
      energy played an important role in photoprotection. Trees with different water
      uses and leaf lifespans appear to employ different photoprotective mechanisms to
      overcome the unfavorable dry-season drought. Our data may suggest that future
      changes in precipitation will strongly impinge on forest structure and functions.

PMID- 24336613
TI  - Dehydrin accumulation and extreme low-temperature tolerance in Siberian spruce
      (Picea obovata).
AB  - To investigate the role of dehydrins (DHNs) in extreme low-temperature (LT)
      tolerance, we sampled needle tissue of Siberian spruce (Picea obovata Ledeb.)
      from trees growing in an arboretum in Trondheim, Norway from August 2006 to April
      2007 and tracked changes in LT tolerance via relative electrolyte leakage. We
      used western blotting to estimate relative amounts of proteins binding a DHN K
      segment antibody, measured relative amounts of nine transcripts for small (<25
      kDa) DHNs by quantitative reverse transcription-polymerase chain reaction (PCR)
      using primers developed for DHN transcripts in a closely related species, Picea
      abies (L.) Karsten, and isolated and sequenced PCR products for five P. obovata
      DHNs. Three protein bands of 53, 35 and 33 kDa were detected on western blots of
      SDS-PAGE-separated protein extracts. The 53-kDa DHN was already present late in
      the growing season, but accumulated during acclimation, and levels decreased
      rapidly during deacclimation. The 33- and 35-kDa proteins, identified as Picg5
      class DHNs by mass spectrometry, first appeared in detectable amounts late in the
      acclimation process and remained at detectable levels throughout the period of
      maximum LT tolerance. Levels of the 53-kDa DHN correlated with two LT tolerance
      parameters, while results for the 33- and 35-kDa proteins were equivocal due to
      limited sample size and variation in LT tolerance during the mid-winter period.
      Three additional bands of 30, 28 and 26 kDa were detected in extracts from
      needles collected in November 2010 using an immunity-purified antibody.
      Immunoblotting of two-dimensional gel electrophoresis gels loaded with proteins
      extracted from October and November samples corroborated the results obtained by
      SDS-PAGE western blots. One large spot in the 53 kDa range and two trains of
      spots in the same size range as the 33 and 35 kDa DHNs were detected using the K
      segment antibody. Eight of the nine DHN transcripts closely tracked LT tolerance
      parameters, whereas the ninth DHN transcripts followed a reverse pattern,
      decreasing during winter and increasing again during deacclimation. Multiple
      regression models using principal components of the transcripts to predict two
      different LT tolerance parameters suggest separate but overlapping functions for
      different DHNs in establishing and maintaining extreme LT tolerance. 

PMID- 24336614
TI  - p-Tolylimido rhenium(V) complexes - synthesis, X-ray studies, spectroscopic
      characterization, DFT calculations and catalytic activity.
AB  - Novel p-tolylimido rhenium(V) complexes trans-(Cl,Cl)-[Re(p-NC6H4CH3)Cl2(py-2
      COO)(PPh3)].MeCN (1a), trans-(Cl,Cl)-[Re(p-NC6H4CH3)Cl2(py-2-COO)(PPh3)] (1b),
      trans-(Br,Br)-[Re(p-NC6H4CH3)Br2(py-2-COO)(PPh3)] (2), cis-(Cl,Cl)-[Re(p
      NC6H4CH3)Cl2(py-2-COO)(PPh3)] (3), cis-(Br,Br)-[Re(p-NC6H4CH3)Br2(py-2
      COO)(PPh3)].H2O (4), trans-(Cl,Cl)-[Re(p-NC6H4CH3)Cl2(OMe)] (5) and trans-(Br,Br)
      [Re(p-NC6H4CH3)Br2(OMe)(PPh3)2].1/2H2O (6) were synthesized. The compounds were
      identified by elemental analysis, IR, NMR ((1)H, (13)C and (31)P), UV-Vis
      spectroscopy and X-ray crystallography. Calculations at the DFT level were
      undertaken in order to elucidate the structural, spectroscopic and bonding
      properties of the trans-(Cl,Cl) and cis-(Cl,Cl) isomers of [Re(p-NC6H4CH3)Cl2(py
      2-COO)(PPh3)]. In the first step, extended tests of the ability of different DFT
      methods (B3LYP, BP86, and PBE1PBE) were performed to find the best overall
      performer in describing the geometry of the imido Re(v) complexes; then, the
      electronic spectra of the trans and cis isomers of [Re(p-NC6H4CH3)Cl2(py-2
      COO)(PPh3)] were investigated at the TDDFT level employing the PBE1PBE
      functional. Additional information about bonding in the compounds [Re(p
      NC6H4CH3)Cl2(py-2-COO)(PPh3)] was obtained by NBO analysis. The catalytic
      activity of the complexes incorporating the picolinate ligand was studied and
      compared in the synthesis of N-substituted ethyl glycine esters from ethyl
      diazoacetate and amines.

PMID- 24336616
TI  - [Morpho-volumetric assessment of the right ventricle: a comparison between three
      dimensional echocardiography and cardiac magnetic resonance].
AB  - The morpho-volumetric assessment of the right ventricle (RV) is useful in the
      diagnosis and prognosis of many congenital and acquired cardiovascular diseases.
      The complexity of the right ventricular shape does not allow an adequate and
      satisfactory evaluation of the RV. Two-dimensional (2D) echocardiography is the
      most used tool for the assessment of RV function, as it is a noninvasive,
      reproducible and widespread technique, but the geometric assumptions required for
      measurement of RV volumes reduce its accuracy. At present, cardiac magnetic
      resonance is the gold standard for the evaluation of RV volumes because it does
      not need any assumption and is reproducible, though not always available. This
      imaging tool allows to follow-up patients and to monitor drug therapy. On the
      other hand, three-dimensional (3D) echocardiography overcomes several limitations
      of 2D echocardiography, in that it provides an estimation of RV volumes obtained
      through a real 3D data set, obtaining sections which cannot be technically
      achieved with 2D echocardiography. It is therefore useful to compare data on RV
      volumes and function obtained with 3D echocardiography versus cardiac magnetic
      resonance, mainly considering the lower costs and higher portability and
      availability of echocardiography. 

PMID- 24336617
TI  - [The Breast Unit in the European and national policy documents: similarities and
      differences].
AB  - Aim of this study is to assess differences and similarities in official European
      and Italian Ministry of Health policy documents referring to the subject "Breast
      Unit". The T-Lab software package for textual analysis was used to analyze the
      documents. This instrument permits the identification of the most frequent used
      words and the semantic network associated with "Breast Unit". Results show that
      the European document gives more emphasis to the concept of "integrated care",
      delivered by a multi-professional team that meets the clinical, psychological and
      informational needs of the patient. The Italian document gives more prominence to
      themes related to the clinical content of the interventions and managerial
      aspects through the use of clinical guidelines. 

PMID- 24336618
TI  - [Echo-Doppler evaluation of recent onset chronic venous insufficiency in elderly
      patients: does the heart have a role?].
AB  - The onset in elderly subjects of clinical signs of chronic venous insufficiency
      (CVI), without a previous history of venous disease of the lower limbs, raises
      questions about the etiology. In our study we evaluated the possible causes
      investigating the venous system of the lower limbs and right heart function in
      elderly subjects with signs of CVI. The alterations found were on the reduction
      of TAPSE, a significantly higher body mass index and a reduced ability to walk
      compared to the control group. The differences described could explain edema and
      skin changes of recent onset. If it is CVI functional type or of congestive heart
      failure in the preclinical stage will be clarified only by adequate follow-up. 

PMID- 24336619
TI  - [Incomplete atrioventricular block in a patient on pregabalin therapy].
AB  - The authors report on a case of incomplete atrio-ventricular block in a patient
      on pregabalin therapy. Pregabalin was not overdosed; renal function of the
      patient was normal. The effect reverted after pregabalin discontinuation. 

PMID- 24336620
TI  - [Idiopathic pulmonary fibrosis: from experimental approach to clinic].
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease
      characterized by interstitial lung fibrosis with involvement of alveoli and
      terminal bronchiole. Its pathogenesis is still unknown, the risk factors involved
      in this disease are still unclear and its prognosis highly unfavorable. The main
      clinical presentations, the major and minor diagnostic criteria, the principal
      hypothesis on the pathogenesis of IPF and the experimental approaches for
      induction of the disease mostly in the murine model will be discussed together
      with current available treatments and ongoing clinical studies on drug therapy. 

PMID- 24336621
TI  - [Recent advances in the diagnosis of vesicoureteral reflux in children].
AB  - Primary vesicoureteral reflux is a common congenital urinary tract abnormality in
      children. There is considerable controversy regarding its management.
      Preservation of kidney function is the main goal treatment, which necessitates
      identification of patients requiring early intervention. The aim of this review
      is to evidence the recent advances in the diagnosis of this congenital
      abnormality and to indicate the guidelines for its diagnostic management. 

PMID- 24336622
TI  - [Endoscopic ultrasound in the diagnosis of pancreatic cystic lesions].
AB  - Pancreatic cystic lesions are increasingly being detected in clinical practice.
      They are commonly asymptomatic and incidentally discovered. Distinction between
      neoplastic and benign lesions is crucial for determining treatment but definite
      diagnosis is often difficult. Endoscopic ultrasound (EUS), with additional EUS
      guided fine needle aspiration (EUS-FNA), has emerged as an ideal technique in the
      evaluation of these lesions. 

PMID- 24336623
TI  - [Role of diagnostic imaging in the diagnosis of acute appendicitis: a comparison
      between ultrasound and computed tomography].
AB  - Acute appendicitis is the most common cause of acute abdomen requiring emergency
      surgery. In particular, it affects patients older than 20 years and diagnosis is
      challenging in this patient subset. The radiologic methods (ultrasound and
      computed tomography) play a key role in the identification, characterization and
      staging of the disease as well as optimal timing of surgery. The aim of our study
      is to assess the usefulness of ultrasound imaging in the diagnosis of acute
      appendicitis and in a retrospective analysis of 54 ultrasound and computed
      tomography exams performed in the emergency department. 

PMID- 24336624
TI  - [The eponyms and the rediscovered family].

PMID- 24336628
TI  - Non-equivalent conformations of D-amino acid oxidase dimer from porcine kidney
      between the two subunits. Molecular dynamics simulation and photoinduced electron
      transfer.
AB  - The structural difference between two subunits of D-amino acid oxidase dimer from
      porcine kidney was studied by molecular dynamics simulation (MDS) and rate of
      photoinduced electron transfer (ET) from aromatic amino acids as tyrosines (Tyr)
      and tryptophanes (Trp) to the excited isoalloxazine (Iso*). The donor-acceptor
      distances (Rc) between isoalloxazine (Iso) and the donors were shortest in Tyr224
      (0.74 nm) in Sub A at 10  degrees C (Sub A10), in Tyr224 (0.79 nm) in Sub B at 10
      degrees C (Sub B10), in Tyr228 (0.85 nm) in Sub A at 30  degrees C (Sub A30),
      and in Tyr224 (0.72 nm) in Sub B at 30  degrees C (Sub B30). The Rcs were mostly
      shorter in the dimer than those in the monomer. Hydrogen bonding (H-bond) pairs
      between Iso and surrounding amino acids varied with the subunit and temperature.
      O2 of the Iso ring formed an H-bond exclusively with Thr317OG1 (side chain) in
      both Sub A10 and Sub A30, while it formed with Gly315N (peptide), Leu316N and
      Thr317N in Sub B10 and Sub B30. N3H of Iso formed an H-bond with Leu51O (peptide)
      in Sub A10 and Sub A30, but not in Sub B10 and Sub B30. Electron affinity of Iso*
      was appreciably lower in Sub A10 compared to Sub B10, while it was opposite at 30
      degrees C. ET rate to Iso* was fastest from Tyr224 in Sub A10, while it was
      fastest from Tyr314 in Sub B10. The ET rate was fastest from Tyr314 in Sub A30,
      while it was fastest from Tyr224 in Sub B30. The greater ET rates in the dimer as
      compared to those in the monomer were elucidated with shorter Rc in the dimer as
      compared to the monomer. The static dielectric constants inside the subunits and
      the static dielectric constant between Iso and Tyr224 or Tyr228 were not
      different appreciably. A few water molecules and sometimes an amino acid were
      located between Iso and Tyr224, which may be the reason why the dielectric
      constant of the entire subunits did not differ from that between Iso and Tyr224.

PMID- 24336629
TI  - Aggressive blood pressure lowering is dangerous: the J-curve: pro side of the
      arguement.

PMID- 24336626
TI  - Dual-targeting pro-apoptotic peptide for programmed cancer cell death via
      specific mitochondria damage.
AB  - Mitochondria are vital organelles to eukaryotic cells. Damage to mitochondria
      will cause irreversible cell death or apoptosis. In this report, we aim at
      programmed cancer cell death via specific mitochondrial damage. Herein, a
      functionalized pro-apoptotic peptide demonstrates a dual-targeting capability
      using folic acid (FA) (targeting agent I) and triphenylphosphonium (TPP) cation
      (targeting agent II). FA is a cancer-targeting agent, which can increase the
      cellular uptake of the pro-apoptotic peptide via receptor-mediated endocytosis.
      And the TPP cation is the mitochondrial targeting agent, which specifically
      delivers the pro-apoptotic peptide to its particular subcellular mitochondria
      after internalized by cancer cells. Then the pro-apoptotic peptide accumulates in
      mitochondria and causes its serious damage. This dual-targeting strategy has the
      potential to effectively transport the pro-apoptotic peptide to targeted cancer
      cell mitochondria, inducing mitochondrial dysfunction and triggering the
      mitochondria-dependent apoptosis to efficiently eliminate cancer cells. 

PMID- 24336630
TI  - Aggressive blood pressure lowering is dangerous: the J-curve: con side of the
      arguement.

PMID- 24336631
TI  - Shifts in coral-assemblage composition do not ensure persistence of reef
      functionality.
AB  - Coral communities are changing rapidly worldwide through loss of coral cover and
      shifts in species composition. Although many reef-building corals are likely to
      decline, some weedy opportunistic species might increase in abundance. Here we
      explore whether the reshuffling of species can maintain ecosystem integrity and
      functioning. Using four common Caribbean reef-building coral genera we modeled
      rates of reef construction and complexity. We show that shifting coral
      assemblages result in rapid losses in coral-community calcification and reef
      rugosity that are independent of changes in the total abundance of reef corals.
      These losses are considerably higher than those recently attributed to climate
      change. Dominance patterns of coral assemblages seem to be the most important
      driver of the functioning of coral reefs and thus, the future of these ecosystems
      might depend not only on reductions of local and global stressors, but also on
      the maintenance of keystone coral species. 

PMID- 24336633
TI  - The translational potential for target validation and therapy using intracellular
      antibodies in oncology.
AB  - Antibody-based molecules can be delivered into cells either by intracellular
      expression or through cellular uptake. We describe technologies for
      identification and expression of intracellular antibodies for target validation,
      intracellular immunization and tumor therapy, such as intracellular antibody
      capture technology, suicide or silencing technology, antigen-antibody interaction
      dependent apoptosis and their application for inhibition of oncogenic
      intracellular proteins and induction of apoptosis. These strategies have to be
      viewed in the context that inhibition of protein-protein interactions by small
      molecules is often limited due to their large interaction surface. We summarize
      antibodies with the ability to penetrate cells and strategies to induce uptake of
      antibodies after modification with protein transduction domains. Interference in
      oncogenic pathways is described for moieties based on antibody 3E10, which
      translocates into the nucleus after extracellular administration. Finally, we
      discuss examples of tumor immunotherapy and vaccination against intracellular
      antigens, and possible interactions mediating their mode of action. 

PMID- 24336634
TI  - Rho kinase proteins regulate global miRNA expression in endothelial cells.
AB  - BACKGROUND: Therapeutic targeting of Rho-Associated, Coiled-Coil Containing
      Protein Kinase (ROCK) signaling for tumor cells and tumor endothelium has shown
      efficacy in pre-clinical tumors models, and a better understanding of how
      proteins regulate tumor progression will strengthen our knowledge over disease
      etiology and treatment of patients with cancer. Recent reports have shown that
      ROCK activity is critical for the expression of a large number of mRNA
      transcripts across multiple cell types including endothelial cells. MATERIALS AND
      METHODS: To examine the effects of ROCK proteins on microRNA (miRNA) expression
      in tumor-forming endothelial cells, we utilized microarrays to evaluate
      expression levels of 1088 miRNAs in vascular tumor-forming endothelial cells
      knocked-down for ROCK1 or ROCK2 or treated with a pharmacological inhibitor of
      ROCK activity. RESULTS: Microarray analysis demonstrated that inhibiting ROCK
      activity altered global miRNA expression. We confirmed our findings using qPCR
      and identified cell-cycle progression, calcium transport, and
      neurogenesis/synaptogenesis as the most highly overrepresented predicted target
      gene networks for the identified miRNAs whose expression was altered by ROCK
      inhibition. CONCLUSION: ROCK signaling induces large-scale changes in global
      miRNA expression and may lead to a better understanding of how these proteins
      affect aberrant vascular states.

PMID- 24336637
TI  - Manipulating the concavity of rhodium nanocubes enclosed by high-index facets via
      site-selective etching.
AB  - Manipulating the degrees of concavity or Miller indices of high-index facets is
      significant for metal nanocrystals to further tailor their properties; however,
      generating a concave surface with negative curvature is still in the early
      development stage and tuning the degree of concavity remains a challenge. Herein,
      we have developed a simple and effective site-selective etching strategy to
      manipulate the concavity of rhodium (Rh) nanocrystals with high-index facets. 

PMID- 24336635
TI  - Brain-metastatic triple-negative breast cancer cells regain growth ability by
      altering gene expression patterns.
AB  - BACKGROUD/AIM: Triple-negative breast cancer (TNBC) frequently metastasizes to
      the brain (BrM). However, genes responsible for BrM of TNBC are yet to be
      identified. MATERIALS AND METHODS: Gene expression profiling of TNBC and BrM was
      conducted, and studies with cultured cells in vitro were performed to verify
      functions of genes identified in these analyses. RESULTS: According to gene
      expression analyses of TNBC and BrM, periplakin (PPL) and mitogen-activated
      protein kinase 13 (MAPK13) were chosen for further investigations. PPL and MAPK13
      were highly expressed in TNBC compared to BrM. While silencing of either PPL or
      MAPK13 in TNBC cells increased cell growth and reduced cell motility,
      overexpression of either PPL or MAPK13 in BrM cells, retarded growth rates and
      facilitated cell motility. CONCLUSION: Gene expression patterns in TNBC and BrM
      reflect cancer cell growth in regions of metastasis.

PMID- 24336638
TI  - Synthesis of heterocycles via transition-metal-catalyzed hydroarylation of
      alkynes.
AB  - Transition-metal (TM)-catalyzed hydroarylation reactions of alkynes have received
      much attention, because they enable the net insertion of alkyne C-C triple bonds
      into C-H bonds of aromatic precursors, resulting in regio- and stereo-selective
      formation of synthetically useful arylalkenes. Taking advantage of this feature,
      TM-catalyzed alkyne hydroarylations have been successfully used for the synthesis
      of heterocycles. TM-catalyzed alkyne hydroarylations can be classified into three
      major categories depending on the type of reaction and precursors involved: (1)
      palladium-catalyzed reductive Heck reactions of alkynes with aryl halides, (2) TM
      catalyzed conjugate arylation reactions of activated alkynes with arylboronic
      acids, and (3) TM-catalyzed aromatic C-H alkenylations with alkynes. This review
      surveys heterocycle synthesis via TM-catalyzed hydroarylation of alkynes
      according to the above classification, with an emphasis on the scope and
      limitations, as well as the underlying mechanisms. 

PMID- 24336639
TI  - Peritoneal dialysis-related peritonitis: twenty-seven years of experience in a
      Colombian medical center.
AB  - Peritonitis has been the most common complication of continues ambulatory
      peritoneal dialysis (CAPD) since it was first implemented, and it remains the
      leading cause of treatment failure and transfer to other renal replacement
      therapies. This study presents a Colombian series with a total of 2,469 episodes
      of peritonitis in 914 patients from a cohort of 1,497 patients on PD, who were
      followed for almost three decades at a single center. This is the largest Latin
      American series of patients with PD-related peritonitis. OBJECTIVE: To describe
      the CAPD-related peritonitis in a cohort of patients followed for 27 years at a
      single center, and compare the results with those observed elsewhere in the
      world. STUDY DESIGN: Prospective study of incident patients on CAPD from March
      1981 to December 2008. RESULTS: In our center, the rate of peritonitis has been
      steady between 0.8 and 0.9 since 1981 and no significant changes have been
      noticed in the 27 years of follow up. The rate remains similar to that described
      nowadays by other large dialysis centers in the world, which have reported
      significant improvements in recent decades. No significant differences were found
      in the isolates of gram-positive and gram-negative microorganisms or fungi with
      respect to those reported by other large series, or in the frequency of culture
      negative peritonitis. CONCLUSION: This study presents the largest Latin American
      series of patients with CAPD-related peritonitis with a total of 2,469 patients.
      In this study, the rate of CAPD-related peritonitis remained almost the same
      during the three decades of observation despite having used three different CAPD
      systems. Our hypothesis is that the socio-economic conditions of the patients
      admitted for peritoneal dialysis influences the rate of peritonitis.

PMID- 24336640
TI  - The first report of The Latin American Society of Nephrology and Hypertension
      (SLANH) Anemia Committee in chronic hemodialysis patients.
AB  - BACKGROUND: Anemia almost invariably occurs in patients with chronic kidney
      disease. Limited data are available regarding anemia management in Latin American
      (LA) hemodialysis (HD) patients. OBJECTIVE: To evaluate the results of the first
      anemia survey of the Anemia Committee of the SLANH. METHODS: This is a
      multinational, voluntary survey that collected anemia management data from adult
      HD patients from independent, non-chain owned HD units, between 09/2009 and
      03/2010. T-test, ANOVA, chi-square test and multivariate logistic regression were
      used for statistical analysis. RESULTS: The survey received responses from 134 HD
      units of 16 countries providing data from 9,025 patients. Mean values of Hb,
      ferritin, and transferrin saturation (TSAT) were 10.5 +/- 1.8 g/dL, 570 +/- 539
      ug/l, and 29.8 +/- 15%, respectively. Only 32.7% of patients were within the Hb
      target of 10.5-12.0 g/dL (46.3% were below and 21.1% above). Erythropoietin
      stimulating agents (ESAs) were administered to 84.3% patients and 68.3% received
      intravenous iron (IV). Iron deficiency (TSAT<=20%) was present in 27.5% patients
      and among those receiving erythropoietin, 47% did not achieve Hb target. The
      independent variables associated with the lowest Hb level (<10.5 g/dL) were:
      female gender, TSAT<25% and age<50 years. CONCLUSIONS: According to these
      results, nearly half of LA chronic HD patients did not achieve the recommended Hb
      target despite wide use of ESAs and IV iron.

PMID- 24336641
TI  - Fungal colonization of an Ordovician impact-induced hydrothermal system.
AB  - Impacts are common geologic features on the terrestrial planets throughout the
      solar system, and on at least Earth and Mars impacts have induced hydrothermal
      convection. Impact-generated hydrothermal systems have been suggested to possess
      the same life supporting capability as hydrothermal systems associated with
      volcanic activity. However, evidence of fossil microbial colonization in impact
      generated hydrothermal systems is scarce in the literature. Here we report of
      fossilized microorganisms in association with cavity-grown hydrothermal minerals
      from the 458 Ma Lockne impact structure, Sweden. Based on morphological
      characteristics the fossilized microorganisms are interpreted as fungi. We
      further infer the kerogenization of the microfossils, and thus the life span of
      the fungi, to be contemporaneous with the hydrothermal activity and migration of
      hydrocarbons in the system. Our results from the Lockne impact structure show
      that hydrothermal systems associated with impact structures can support
      colonization by microbial life. 

PMID- 24336642
TI  - ChAMP: 450k Chip Analysis Methylation Pipeline.
AB  - The Illumina Infinium HumanMethylation450 BeadChip is a new platform for high
      throughput DNA methylation analysis. Several methods for normalization and
      processing of these data have been published recently. Here we present an
      integrated analysis pipeline offering a choice of the most popular normalization
      methods while also introducing new methods for calling differentially methylated
      regions and detecting copy number aberrations. AVAILABILITY AND IMPLEMENTATION:
      ChAMP is implemented as a Bioconductor package in R. The package and the vignette
      can be downloaded at bioconductor.org

PMID- 24336643
TI  - BETASEQ: a powerful novel method to control type-I error inflation in partially
      sequenced data for rare variant association testing.
AB  - SUMMARY: Despite its great capability to detect rare variant associations, next
      generation sequencing is still prohibitively expensive when applied to large
      samples. In case-control studies, it is thus appealing to sequence only a subset
      of cases to discover variants and genotype the identified variants in controls
      and the remaining cases under the reasonable assumption that causal variants are
      usually enriched among cases. However, this approach leads to inflated type-I
      error if analyzed naively for rare variant association. Several methods have been
      proposed in recent literature to control type-I error at the cost of either
      excluding some sequenced cases or correcting the genotypes of discovered rare
      variants. All of these approaches thus suffer from certain extent of information
      loss and thus are underpowered. We propose a novel method (BETASEQ), which
      corrects inflation of type-I error by supplementing pseudo-variants while keeps
      the original sequence and genotype data intact. Extensive simulations and real
      data analysis demonstrate that, in most practical situations, BETASEQ leads to
      higher testing powers than existing approaches with guaranteed (controlled or
      conservative) type-I error. AVAILABILITY AND IMPLEMENTATION: BETASEQ and
      associated R files, including documentation, examples, are available at
      http://www.unc.edu/~yunmli/betaseq

PMID- 24336644
TI  - VIRAPOPS: a forward simulator dedicated to rapidly evolved viral populations.
AB  - SUMMARY: Daily, mutability and recombination of RNA viruses result in the
      production of million variants. All these rapid genomic changes directly
      influence the functional sites of the protein, its 3D structure or its drug
      resistances. Therefore, it is important to simulate these drastic switches to
      determine their effects on virus populations. Many computer programs are able to
      simulate specific variations in DNA genomes, but are generally non-adapted to RNA
      viruses. They simulate site-specific selection pressures, but rarely pressures on
      covariant or on higher order correlated sites and no at all on synthetic lethal
      groups. That is why we felt it important to create VIRAPOPS, a forward simulator
      that models specific RNA virus functions. It was designed for computational
      biologists, biologists and virologists. AVAILABILITY AND IMPLEMENTATION: Free
      binaries are available through a software repository at
      http://petitjeanmichel.free.fr/itoweb.petitjean.freeware.html.

PMID- 24336645
TI  - PhenoMan: phenotypic data exploration, selection, management and quality control
      for association studies of rare and common variants.
AB  - MOTIVATION: Next-generation sequencing and other high-throughput technology
      advances have promoted great interest in detecting associations between complex
      traits and genetic variants. Phenotype selection, quality control (QC) and
      control of confounders are crucial and can have a great impact on the ability to
      detect associations. Although there are programs to perform association analyses,
      e.g. PLINK and GenABEL, they cannot be used for comprehensive management and QC
      of phenotype data. To address this need PhenoMan was developed: to select
      individuals based on multiple phenotype criteria or population membership;
      control for missing covariate data; remove related individuals, duplicate samples
      and individuals with incorrect sex specification; recode primary traits and
      covariates; transform data; remove or winsorize outliers; select covariates for
      analysis; and create residuals. To ensure consistency and harmonization between
      analyses, a report is generated for every dataset. Summary statistics are also
      provided in graphical or text format. PhenoMan can be used for selection and
      manipulation of quantitative, disease and control data. SUMMARY: Phenoman is
      freeware that provides approaches for efficient exploration and management of
      phenotype data. Proper QC of phenotypes before proceeding to the association
      analysis is critical to ensure control of type I and II errors, reliable effect
      estimates and consistent results between studies. PhenoMan is highly beneficial
      for the preparation of qualitative and quantitative trait data for association
      studies using new datasets as well as those obtained from public repositories.
      AVAILABILITY AND IMPLEMENTATION: code.google.com/p/phenoman

PMID- 24336647
TI  - Genes related to differentiation are correlated with the gene regulatory network
      structure.
AB  - MOTIVATION: Many secondary messengers, receptors and transcription factors are
      related to cell differentiation. Their role in cell differentiation can be
      affected by their position in the gene regulatory network. Here, we test whether
      the properties of the gene regulatory network can highlight which genes and
      proteins are associated with cell differentiation. We use a previously developed
      purely theoretical algorithm built to detect nodes that can induce a state change
      in Boolean gene regulatory networks, and show that most genes predicted to
      participate in differentiation in the theoretical framework are also
      experimentally known to be associated with such differentiation. These results
      show that genes related to differentiation are associated with specific features
      of the genetic regulatory network. The proposed algorithm produces a better
      classification than simple network measures such as the nodes degree or
      centrality. Boolean networks were used in many previous theoretical models. Here,
      we show a direct application of such networks to the detection of genes and
      subnetworks related to differentiation. The subnetwork emerging from the genes
      and edges that are predicted to be associated with differentiation are the most
      active molecular pathways experimentally described to be involved in cell
      differentiation. AVAILABILITY AND IMPLEMENTATION:
      http://peptibase.cs.biu.ac.il/homepage/Boolean_network_conversion_code.zip.

PMID- 24336646
TI  - Sequence-based Gaussian network model for protein dynamics.
AB  - MOTIVATION: Gaussian network model (GNM) is widely adopted to analyze and
      understand protein dynamics, function and conformational changes. The existing
      GNM-based approaches require atomic coordinates of the corresponding protein and
      cannot be used when only the sequence is known. RESULTS: We report, first of its
      kind, GNM model that allows modeling using the sequence. Our linear regression
      based, parameter-free, sequence-derived GNM (L-pfSeqGNM) uses contact maps
      predicted from the sequence and models local, in the sequence, contact
      neighborhoods with the linear regression. Empirical benchmarking shows relatively
      high correlations between the native and the predicted with L-pfSeqGNM B-factors
      and between the cross-correlations of residue fluctuations derived from the
      structure- and the sequence-based GNM models. Our results demonstrate that L
      pfSeqGNM is an attractive platform to explore protein dynamics. In contrast to
      the highly used GNMs that require protein structures that number in thousands,
      our model can be used to study motions for the millions of the readily available
      sequences, which finds applications in modeling conformational changes, protein
      protein interactions and protein functions.

PMID- 24336648
TI  - Evaluation of adherence to a convulsion management protocol for children in
      Rwanda.
AB  - Inappropriate seizure management may result in high morbidity and mortality. We
      assessed the adherence of health professionals in southern Rwanda to a national
      protocol for pharmacological management of seizures in children. A questionnaire
      featuring a 5-year-old child with generalized prolonged seizures was
      administered. The questions focused on the choice of initial treatment and the
      sequence of management following failure of the initial treatment choice.
      Benzodiazepine was chosen as initial therapy by 93.7% of physicians and 90.9% of
      nurses. Only 49.2% of physicians and 41% of nurses would repeat the initial
      treatment in case of failure of the first dose and 47% of doctors would wait 30
      min to intervene. In case of refractory status epilepticus, 34% of physicians
      would give three doses of benzodiazepine, whereas 19% did not know what to do.
      These results suggest poor adherence to national protocol. 

PMID- 24336649
TI  - Effects of chronic exposure to cigarette smoke on canonical transient receptor
      potential expression in rat pulmonary arterial smooth muscle.
AB  - To clarify the possible mechanism of cigarette smoke (CS)-induced pulmonary
      hypertension and furthermore provide effective targets for prevention and
      treatment, the effects of chronic CS on rat pulmonary arterial smooth muscle in
      vivo and nicotine treatment on rat pulmonary arterial smooth muscle cells
      (PASMCs) in vitro were investigated. In this study, we demonstrated that chronic
      CS exposure led to rat weight loss, right ventricular hypertrophy, and pulmonary
      arterial remodeling. A fluorescence microscope was used to measure intracellular
      calcium concentration ([Ca(2+)]i) in rat distal PASMCs. Results showed that basal
      [Ca(2+)]i and store-operated calcium entry (SOCE) levels in PASMCs from 3- and 6
      mo CS-exposed rats were markedly higher than those in cells from the unexposed
      control animals (the increases in 6-mo CS group were more significant than that
      in 3-mo group), accompanied with increased canonical transient receptor potential
      1 (TRPC1) and TRPC6 expression at both mRNA and protein levels in isolated distal
      PA. Simultaneously, in vitro study showed that nicotine treatment (10 nM)
      significantly increased basal [Ca(2+)]i and SOCE and upregulated TRPC1 and TRPC6
      expression in cultured rat distal PASMCs. TRPC siRNA knockdown strategies
      revealed that the elevations of basal [Ca(2+)]i and SOCE induced by nicotine in
      PASMCs were TRPC1 and TRPC6 dependent. These results suggested that chronic CS
      induced changes in vascular tone and structure in PA and the development of
      pulmonary hypertension might be largely due to upregulation of TRPC1 and TRPC6
      expression in PASMCs, in which nicotine played an important role. 

PMID- 24336650
TI  - The hyperglycemic and hyperinsulinemic combo gives you diabetic kidney disease
      immediately. Focus on "Combined acute hyperglycemic and hyperinsulinemic clamp
      induced profibrotic and proinflammatory responses in the kidney".

PMID- 24336651
TI  - miR-23a is decreased during muscle atrophy by a mechanism that includes
      calcineurin signaling and exosome-mediated export.
AB  - Skeletal muscle atrophy is prevalent in chronic diseases, and microRNAs (miRs)
      may play a key role in the wasting process. miR-23a was previously shown to
      inhibit the expression of atrogin-1 and muscle RING-finger protein-1 (MuRF1) in
      muscle. It also was reported to be regulated by cytoplasmic nuclear factor of
      activated T cells 3 (NFATc3) in cardiomyocytes. The objective of this study was
      to determine if miR-23a is regulated during muscle atrophy and to evaluate the
      relationship between calcineurin (Cn)/NFAT signaling and miR-23a expression in
      skeletal muscle cells during atrophy. miR-23a was decreased in the gastrocnemius
      of rats with acute streptozotocin-induced diabetes, a condition known to increase
      atrogin-1 and MuRF1 expression and cause atrophy. Treatment of C2C12 myotubes
      with dexamethasone (Dex) for 48 h also reduced miR-23a as well as RCAN1.4 mRNA,
      which is transcriptionally regulated by NFAT. NFATc3 nuclear localization and the
      amount of miR-23a decreased rapidly within 1 h of Dex administration, suggesting
      a link between Cn signaling and miR-23a. The level of miR-23a was lower in
      primary myotubes from mice lacking the alpha- or beta-isoform of the CnA
      catalytic subunit than wild-type mice. Dex did not further suppress miR-23a in
      myotubes from Cn-deficient mice. Overexpression of CnAbeta in C2C12 myotubes
      prevented Dex-induced suppression of miR-23a. Finally, miR-23a was present in
      exosomes isolated from the media of C2C12 myotubes, and Dex increased its
      exosomal abundance. Dex did not alter the number of exosomes released into the
      media. We conclude that atrophy-inducing conditions downregulate miR-23a in
      muscle by mechanisms involving attenuated Cn/NFAT signaling and selective
      packaging into exosomes. 

PMID- 24336652
TI  - Conditions that promote primary human skeletal myoblast culture and muscle
      differentiation in vitro.
AB  - Conditions under which skeletal myoblasts are cultured in vitro are critical to
      growth and differentiation of these cells into mature skeletal myofibers. We
      examined several culture conditions that promoted human skeletal myoblast (HSkM)
      culture and examined the effect of microRNAs and mechanical stimulation on
      differentiation. Culture conditions for HSkM are different from those that enable
      rapid C2C12 myoblast differentiation. Culture on a growth factor-reduced Matrigel
      (GFR-MG)-coated surface in 2% equine serum-supplemented differentiation medium to
      promote HSkM differentiation under static conditions was compared with culture
      conditions used for C2C12 cell differentiation. Such conditions led to a >20-fold
      increase in myogenic miR-1, miR-133a, and miR-206 expression, a >2-fold increase
      in myogenic transcription factor Mef-2C expression, and an increase in sarcomeric
      alpha-actinin protein. Imposing +/-10% cyclic stretch at 0.5 Hz for 1 h followed
      by 5 h of rest over 2 wk produced a >20% increase in miR-1, miR-133a, and miR-206
      expression in 8% equine serum and a >35% decrease in 2% equine serum relative to
      static conditions. HSkM differentiation was accelerated in vitro by inhibition of
      proliferation-promoting miR-133a: immunofluorescence for sarcomeric alpha-actinin
      exhibited accelerated development of striations compared with the corresponding
      negative control, and Western blotting showed 30% more alpha-actinin at day 6
      postdifferentiation. This study showed that 100 MUg/ml GFR-MG coating and 2%
      equine serum-supplemented differentiation medium enhanced HSkM differentiation
      and myogenic miR expression and that addition of antisense miR-133a alone can
      accelerate primary human skeletal muscle differentiation in vitro. 

PMID- 24336653
TI  - Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in
      female mice.
AB  - Acid-sensing ion channels (ASIC) open in response to extracellular acidosis.
      ASIC1a, a particular subtype of these channels, has been described to have a
      postsynaptic distribution in the brain, being involved not only in ischemia and
      epilepsy, but also in fear and psychiatric pathologies. High-frequency
      stimulation of skeletal motor nerve terminals (MNTs) can induce presynaptic pH
      changes in combination with an acidification of the synaptic cleft, known to
      contribute to muscle fatigue. Here, we studied the role of ASIC1a channels on
      neuromuscular transmission. We combined a behavioral wire hanging test with
      electrophysiology, pharmacological, and immunofluorescence techniques to compare
      wild-type and ASIC1a lacking mice (ASIC1a (-/-) knockout). Our results showed
      that 1) ASIC1a (-/-) female mice were weaker than wild type, presenting shorter
      times during the wire hanging test; 2) spontaneous neurotransmitter release was
      reduced by ASIC1a activation, suggesting a presynaptic location of these channels
      at individual MNTs; 3) ASIC1a-mediated effects were emulated by extracellular
      local application of acid saline solutions (pH = 6.0; HEPES/MES-based solution);
      and 4) immunofluorescence techniques revealed the presence of ASIC1a antigens on
      MNTs. These results suggest that ASIC1a channels might be involved in controlling
      neuromuscular transmission, muscle contraction and fatigue in female mice. 

PMID- 24336655
TI  - "S'ils n'ont pas de pain, qu'ils mangent de la brioche." Focus on "anaerobic
      respiration sustains mitochondrial membrane potential in a prolyl hydroxylase
      pathway-activated cancer cell line in a hypoxic microenvironment".

PMID- 24336654
TI  - Intracellular Ca2+ oscillations generated via the Ca2+-sensing receptor are
      mediated by negative feedback by PKCalpha at Thr888.
AB  - To clarify the mechanism(s) underlying intracellular Ca(2+) concentration
      ([Ca(2+)]i) oscillations induced by an elevation in extracellular Ca(2+)
      concentration ([Ca(2+)]e) via the extracellular Ca(2+)-sensing receptor (CaR), we
      analyzed the pattern of [Ca(2+)]i response in multiple (2,303) individual HEK-293
      cells transfected with the human CaR. An increase in the [Ca(2+)]e from 1.5 to 3
      mM produced oscillatory fluctuations in [Ca(2+)]i in 70% of the cell population.
      To determine the role of PKC in the generation of [Ca(2+)]i oscillations, cells
      were exposed to increasing concentrations (0.5-5 MUM) of the preferential PKC
      inhibitor Ro-31-8220 before stimulation by extracellular Ca(2+). Ro-31-8220 at 3
      5 MUM completely eliminated the [Ca(2+)]e-evoked [Ca(2+)]i oscillations and
      transformed the pattern to a peak and sustained plateau response. Treatment with
      other broad PKC inhibitors, including GFI or Go6983, produced an identical
      response. Similarly, treatment with Ro-31-8220 or GFI eliminated [Ca(2+)]e-evoked
      [Ca(2+)]i oscillations in colon-derived SW-480 cells expressing the CaR.
      Treatment with inhibitors targeting classic PKCs, including Go6976 and Ro-32-0432
      as well as small interfering RNA-mediated knockdown of PKCalpha, strikingly
      reduced the proportion of cell displaying [Ca(2+)]e-evoked [Ca(2+)]i
      oscillations. Furthermore, none of the cells analyzed expressing a CaR mutant in
      which the major PKC phosphorylation site Thr(888) was converted to alanine
      (CaRT888A) showed [Ca(2+)]i oscillations after CaR activation. Our results show
      that [Ca(2+)]i oscillations induced by activation of the CaR in response to an
      increase in extracellular Ca(2+) or exposure to the calcimimetic R-568 result
      from negative feedback involving PKCalpha-mediated phosphorylation of the CaR at
      Thr(888). 

PMID- 24336658
TI  - 'A conversation without words'--reflections on music therapy and dementia.

PMID- 24336657
TI  - Interferon-gamma suppresses activin A/NF-E2 induction of erythroid gene
      expression through the NF-kappaB/c-Jun pathway.
AB  - Interferon (IFN)-gamma is a proinflammatory cytokine that is linked to
      erythropoiesis inhibition and may contribute to anemia. However, the mechanism of
      IFN-gamma-inhibited erythropoiesis is unknown. Activin A, a member of the
      transforming growth factor (TGF)-beta superfamily, induces the erythropoiesis of
      hematopoietic progenitor cells. In this study, a luciferase reporter assay showed
      that IFN-gamma suppressed activin A-induced zeta-globin promoter activation in
      K562 erythroblast cells in a dose-dependent manner. Activin A reversed the
      suppressive effect of IFN-gamma on the luciferase activity of zeta-globin
      promoter in a dose-dependent manner. IFN-gamma also suppressed the activation of
      activin A-induced alpha-globin promoter. IFN-gamma reduced the mRNA expression of
      alpha-globin, zeta-globin, NF-E2p45, and GATA-1 induced by activin A. The results
      also showed that IFN-gamma induced c-Jun expression when NF-kappaBp65 and c-Jun
      bound to two AP-1-binding sites on the c-Jun promoter. The luciferase activity of
      alpha-globin and zeta-globin promoters were enhanced by wild-type c-Jun and
      eliminated by dominant-negative (DN) c-Jun. The suppressive effects of IFN-gamma
      on the mRNA expression of alpha-globin and zeta-globin were absent in cells
      expressing DN c-Jun. The ability of NF-E2 to enhance activin A-induced zeta
      globin promoter activation decreased when c-Jun was present, and IFN-gamma
      treatment further enhanced the decreasing effect of c-Jun. Chromatin
      immunoprecipitation revealed that NF-E2p45 bound to the upstream regulatory
      element (HS-40) of the alpha-globin gene cluster in response to activin A,
      whereas c-Jun eliminated this binding. These results suggest that IFN-gamma
      modulates NF-kappaB/c-Jun to antagonize activin A-mediated NF-E2 transcriptional
      activity on globin gene expression. 

PMID- 24336656
TI  - Secreted Frizzled-related protein 2 as a target in antifibrotic therapeutic
      intervention.
AB  - Progressive fibrosis is a pathological hallmark of many chronic diseases
      responsible for organ failure. Although there is currently no therapy on the
      market that specifically targets fibrosis, the dynamic fibrogenic process is
      known to be regulated by multiple soluble mediators that may be therapeutically
      intervened. The failing hamster heart exhibits marked fibrosis and increased
      expression of secreted Frizzled-related protein 2 (sFRP2) amenable to reversal by
      mesenchymal stem cell (MSC) therapy. Given the previous demonstration that sFRP2
      null mice subjected to myocardial infarction exhibited reduced fibrosis and
      improved function, we tested whether antibody-based sFRP2 blockade might
      counteract the fibrogenic pathway and repair cardiac injury. Cardiomyopathic
      hamsters were injected intraperitoneally twice a week each with 20 MUg of sFRP2
      antibody. Echocardiography, histology, and biochemical analyses were performed
      after 1 mo. sFRP2 antibody increased left ventricular ejection fraction from 40
      +/- 1.2 to 49 +/- 6.5%, whereas saline and IgG control exhibited a further
      decline to 37 +/- 0.9 and 31 +/- 3.2%, respectively. Functional improvement is
      associated with a ~ 50% reduction in myocardial fibrosis, ~ 65% decrease in
      apoptosis, and ~ 75% increase in wall thickness. Consistent with attenuated
      fibrosis, both MSC therapy and sFRP2 antibody administration significantly
      increased the activity of myocardial matrix metalloproteinase-2. Gene expression
      analysis of the hamster heart and cultured fibroblasts identified Axin2 as a
      downstream target, the expression of which was activated by sFRP2 but inhibited
      by therapeutic intervention. sFRP2 blockade also increased myocardial levels of
      VEGF and hepatocyte growth factor (HGF) along with increased angiogenesis. These
      findings highlight the pathogenic effect of dysregulated sFRP2, which may be
      specifically targeted for antifibrotic therapy.

PMID- 24336659
TI  - The role of the bilingual/bicultural worker in dementia education, support and
      care.
AB  - Members of minority populations often have difficulty knowing about and accessing
      dementia services. One of the strategies used to promote access is the employment
      of bilingual/bicultural workers (sometimes referred to as multicultural, link or
      outreach workers). This study involved interviews with 24 bilingual/bicultural
      workers in south western Sydney, Australia to gain a better understanding of
      their role within the dementia field. Seven themes emerged: importance of working
      with family; process of building trust when moving between two cultures;
      importance of understanding the culture; self-care and culture; flexibility of
      their role; linking community members; and linking communities to mainstream
      services. Bilingual/bicultural workers play a significant and complex role in
      supporting individuals and families within their community who are affected by
      dementia. The significance of their role needs to be more clearly acknowledged in
      the development of policy, further research and service provision within the
      dementia field. 

PMID- 24336660
TI  - Dementia research--what do different public groups want? A survey by the Scottish
      Dementia Clinical Research Network.
AB  - Scotland's National Dementia Strategy calls for people with dementia and their
      carers to give voice to what they see as the priorities for dementia research. We
      sent questionnaires on dementia research priorities, locus and type of research,
      desired outcome measures and willingness to volunteer, to two groups of dementia
      research stakeholders: (1) people with dementia and their carers who may or may
      not be participating in research and (2) those who are directly participating in
      research. We also made the questionnaire available on a national dementia
      research website. Five hundred and fourteen responses were received. The top four
      topics rated by importance were identical across all three groups of respondents:
      early detection (38.1%), drug trials (14.2%), studies on people living at home
      (9.7%) and study of carers (6.0%). The data can help shape the dementia research
      agenda, but more information needs to be made available to the public about other
      potential research areas. 

PMID- 24336662
TI  - Trajectories of care: spouses coping with changes related to mild cognitive
      impairment.
AB  - Mild cognitive impairment (MCI) refers to non-normative changes in memory and
      cognition. While researchers are beginning to address the social consequences of
      MCI, no investigations have tracked how married couples respond to MCI over time
      as symptoms stabilize or become more severe. Guided by life course and symbolic
      interactionist tenets, we examined how 40 older couples in the United States
      adjusted to daily life after one partner was diagnosed with MCI and how their
      marital roles and relationship changed over a three- to four-year period. Data
      were collected from 2004 through 2010. All couples experienced an initial period
      of transition in coping with MCI where they made adjustments in their daily lives
      and interactions. Following this adjustment period, four trajectories of care
      emerged depending on the extent of the older adult's decline and the spouse's
      response. We conclude that changes associated with MCI affect role identity and
      have consequences for spousal relationships. 

PMID- 24336661
TI  - Dementia skills for all: a core competency framework for the workforce in the
      United Kingdom.
AB  - One of the biggest challenges facing health and social care in the United Kingdom
      is the projected increase in the number of older people who require dementia
      care. The National Dementia Strategy (Department of Health, 2009) emphasizes the
      critical need for a skilled workforce in all aspects of dementia care. In the
      West Midlands, the Strategic Health Authority commissioned a project to develop a
      set of generic core competencies that would guide a competency based curriculum
      to meet the demands for improved dementia training and education. A systematic
      literature search was conducted to identify relevant frameworks to assist with
      this work. The core competency framework produced and the methods used for the
      development of the framework are presented and discussed. 

PMID- 24336663
TI  - Creating relationships with persons with moderate to severe dementia.
AB  - The study describes how relationships are created with persons with moderate to
      severe dementia. The material comprises 24 video sequences of Relational Time
      (RT) sessions, 24 interviews with persons with dementia and eight interviews with
      professional caregivers. The study method was Constructivist Grounded Theory. The
      categories of 'Assigning time', 'Establishing security and trust' and
      'Communicating equality' were strategies for arriving at the core category,
      'Opening up', which was the process that led to creating relationships. Both
      parties had to contribute to create a relationship; the professional caregiver
      controlled the process, but the person with dementia permitted the caregiver's
      overtures and opened up, thus making the relationship possible. Interpersonal
      relationships are significant to enhancing the well-being of persons with
      dementia. Small measures like RT that do not require major resources can open
      paths to creating relationships. 

PMID- 24336664
TI  - Long-term effects of group therapy for patients with mild cognitive impairment
      and their significant others: a 6- to 8-month follow-up study.
AB  - The present study examines the long-term effects of a 10-session cognitive
      behavioural group therapy for patients with mild cognitive impairment (MCI) and
      their significant others 6 to 8 months after completion of the intervention.
      Forty-seven MCI patients and 47 significant others participated in the follow-up
      assessment. Results of the RAND-36, Illness Cognition Questionnaire, IQCODE, GDS
      15 and Sense of Competence Questionnaire at follow-up were compared with the post
      intervention assessment. Our findings showed that the increased level of
      acceptance in the MCI patients was maintained at follow-up, with an increased
      insight into their cognitive decline compared with post-intervention assessment
      (p < 0.001). In both the patients and the significant others, helplessness and
      wellbeing were worse at follow up (p < 0.05), but sense of competence increased
      in the significant others (p < 0.05). These results indicate a need for extension
      of the support after completion of the program, for example by providing regular
      booster sessions. 

PMID- 24336665
TI  - Education on physical restraint reduction in dementia care: a review of the
      literature.
AB  - Dementia is a priority area for all countries as populations age and dementia
      prevalence increases. The use of physical restraint is a possible clinical
      practice for persons with dementia across settings when behaviours indicate a
      perceived need. Indeed, this may be the first choice in practice, occurring in
      part because of lack of education, safety concerns, perceived costs and staffing
      issues. This article reviews the literature on the issues surrounding, and use
      of, physical restraint for people with dementia, highlighting the rationales for
      use and the benefits and barriers to physical restraint. Recommendations include
      the importance of education and policy to reduce or eliminate physical restraint
      of persons with dementia to overcome identified barriers at the individual,
      cultural and organizational levels. An educational programme from the literature
      review is proposed specific to the reduction or elimination of physical
      restraint. 

PMID- 24336666
TI  - Ethical and effective: approaches to residential care for people with dementia.
AB  - New knowledge underpins calls for change in approaches to the care of people with
      dementia. Person-centred care is considered essential, whereas purpose-built
      facilities and environmental design are reported to enhance safety and to have a
      positive effect on behaviour. Research findings have highlighted the
      inappropriate use of antipsychotic drugs and there is debate about their value in
      'managing' symptoms. This paper presents the combination of approaches used to
      enable residents of two secure dementia units to live life within their ability
      and without antipsychotic drugs. Essential to the success of the change process
      was staff education, knowledge of the person, a varied leisure activity programme
      and a supportive environment. Evidence of the positive difference these
      strategies made includes statistics that show a decline in falls and behavioural
      issues, and feedback from family members. In light of the evidence, this article
      posits that it is ethically wrong to give people with dementia antipsychotic
      medications because their behaviour is deemed to be unacceptable, when there are
      other viable options. 

PMID- 24336667
TI  - Living alone with dementia.
AB  - This paper details the findings of an exploratory study undertaken in 2009 into
      the older population who live alone with dementia, as part of a wider study into
      the phenomenon of living alone in older age with a cognitive impairment or early
      stage dementia. Interviews were undertaken with 19 older people who live alone
      with cognitive impairment or early stage dementia, and field notes were taken
      during interview visits. Throughout this paper, older people who live alone with
      a cognitive impairment or dementia who participated in the study will be referred
      to by pseudonym. Overall, the findings give insight into the lives of these
      people and how they remain connected to and supported by others. These findings
      will contribute to the knowledge of this group, which may be considered in future
      research and service delivery. 

PMID- 24336668
TI  - The ambiguous relationships between aging and Alzheimer's disease: a critical
      literature review.
AB  - One reason for the rise in the prevalence of Alzheimer's disease (AD) since the
      1980s is the new association between the disease and aging. This paper explores
      the current representations of AD, questioning their relationships to aging,
      thanks to a literature review of 49 articles published in French and in English
      between 1995 and June 2010. Aging appears to be a concurrent diagnosis for AD,
      both for the lay public and for health professionals, but this confusion, which
      can be interpreted as a lack of medicalization of memory loss on the conceptual
      level, does not necessarily constitute an obstacle to medical intervention. The
      transformation of senile dementia into AD can diminish, as well as reinforce,
      stigmatization of people with AD. Moreover, elderly people with AD are subjected
      to both the persisting stigmas of aging and of dementia as well as, for most of
      them, that of feminine cognitive incompetence. 

PMID- 24336670
TI  - Costimulatory molecule CD28 participates in the process of embryo implantation in
      mice.
AB  - Embryo implantation is a complex process requiring reciprocal interactions
      between implantation-competent blastocysts and receptive uteri. Accumulating
      literatures have indicated that T cells are involved in this process. The first
      signal mediated by T-cell receptor/CD3 complex and the second signal delivered by
      costimulatory molecules are essential for the differentiation of T cell into an
      effector cell. Expression and function of CD28, an important costimulatory
      molecule, during early pregnancy in mice is still unclear. In the present study,
      we investigated the expression pattern of CD28 in mouse uterus during early
      pregnancy and pseudopregnancy by real-time quantitative polymerase chain
      reaction, Western blotting, in situ hybridization, and immunohistochemistry
      (IHC). We found that injection of the uterine horn with CD28 antisense
      oligodeoxynucleotides leads to a decreased number of implantation sites. The
      expression pattern of CD3 protein examined by IHC is similar to that of CD28.
      These findings suggest that CD28 participates in the process of embryo
      implantation in mice, which might play its role through delivering the second
      costimulatory signal. 

PMID- 24336671
TI  - Expression of notch family proteins in placentas from patients with early-onset
      severe preeclampsia.
AB  - OBJECTIVES: This study is aimed to identify the expression of Notch family
      proteins in placentas from patients with early-onset severe preeclampsia. STUDY
      DESIGN: The expression of Notch family proteins in placentas was investigated by
      immunohistochemistry, Western blotting, and real-time reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: The profile of distribution of all
      Notch family proteins in placentas from patients with early-onset severe
      preeclampsia is similar to that in normal placentas. All Notch family proteins
      are expressed in placental trophoblasts. Moreover, Notch1 and Jagged1 (Jag1) are
      detected in placental endothelial cells. Real-time RT-PCR showed that messenger
      RNA levels of Notch2 and Delta-like4 (Dll4) in placentas from patients with early
      onset severe preeclampsia are lower than that of normal placentas. Western
      blotting showed a significant increase in Notch3 expression and a significant
      decrease in Notch2 expression in placentas from patients with early-onset severe
      preeclampsia relative to those in normal placentas. CONCLUSION: The results
      suggest that Notch2 and Notch3 may play some roles in the pathogenesis of
      preeclampsia.

PMID- 24336672
TI  - Roles of sphingosine-1-phosphate in reproduction.
AB  - Sphingosine-1-phosphate (S1P) plays crucial roles in the regulation of cell
      growth, proliferation, differentiation, cell survival, migration, and
      angiogenesis. In the reproductive system, S1P protects mammalian germ cells from
      irradiation or chemotherapy-induced cell death in vivo and in vitro. Moreover,
      S1P could improve the survival rate of thawed ovary and transplanted ovary.
      Furthermore, S1P could improve the developmental potential of oocyte and
      preimplantation embryo. In conclusion, S1P plays important roles in reproduction.

PMID- 24336673
TI  - Progesterone regulates secretin expression in mouse uterus during early
      pregnancy.
AB  - Secretin, a classical gastrointestinal and neuroendocrine peptide, plays an
      important role in maintaining the body fluid balance. However, the expression and
      regulation of secretin in the reproductive system are still unknown. In our
      study, secretin is specifically expressed in the decidua on days 5 to 8 of
      pregnancy. Secretin expression is not detected under delayed implantation but is
      stimulated after estrogen activation and under artificial decidualization.
      Progesterone induces secretin expression in ovariectomized mice and cultured
      stromal cells, which is abrogated by specific LY294002. Because secretin is
      mainly localized in the decidua and also strongly expressed during in vitro
      decidualization, secretin may play a role during mouse decidualization through
      regulating cyclic adenosine monophosphate level. 

PMID- 24336675
TI  - Impact of Highly Active Antiretroviral Therapy on the Natural History of Cervical
      Precancerous Lesions: A 17-Year Institutional Longitudinal Cohort Study.
AB  - We performed an observational cohort study in order to assess the correlation
      between precancerous cervical lesions (cervical intraepithelial neoplasia [CIN])
      and immunological state in human immunodeficiency virus (HIV)-positive women
      treated by highly active antiretroviral therapy (HAART). We analyzed 194 HIV
      infected women referred to the Parma-Universitary Hospital for early detection of
      human papilloma virus-induced CINs. We analyzed cytology, colposcopy, and CIN
      degree according to HAART: group A untreated and group B treated. We compared the
      CD4+ count and viral load at the time of CIN onset and the time interval between
      diagnosis of HIV and the onset of CIN. Group A and group B showed homogeneous
      results for general features, CD4+ count, viral load, and Papanicolaou test
      features. Differences were not found in terms of histology and CD4+ value, viral
      load count, pharmacological treatment, years since the diagnosis of HIV, age,
      smoking, sexual promiscuity, previous intravenous narcotics abuse, prostitution,
      sexually transmitted diseases, ethnicity, and age at diagnosis. Histology and the
      clinical stage of HIV showed significant concordances between the high degree of
      cervical dysplasia and advanced stage of HIV disease.

PMID- 24336674
TI  - Mmu-miR-193 is involved in embryo implantation in mouse uterus by regulating GRB7
      gene expression.
AB  - Embryo implantation is a complicated process involving a series of endometrial
      changes that depend on differential gene expression. MicroRNAs (miRNAs) are
      important for regulation of gene expression. Previous studies have shown that
      miRNAs may participate in the regulation of gene expression during embryo
      implantation. To explore the role of endometrial miRNAs in early murine
      pregnancy, we used microarrays to investigate whether miRNAs were differentially
      expressed in the mouse endometrium on pregnancy day 4 (D4) and day 6 (D6). The
      results demonstrated that 17 miRNAs were upregulated and 18 were downregulated
      (>2-fold) in D6 endometria compared to D4. We identified that mmu-miR-193
      exhibited the highest upregulation on D6, and the upregulation of mmu-miR-193
      before embryo implantation could reduce the embryo implantation rate. Further, we
      demonstrated that mmu-miR-193 influenced embryo implantation by regulating growth
      factor receptor-bound protein 7 expression. In summary, our study suggests that
      mmu-miR-193 plays an important role in embryo implantation. 

PMID- 24336676
TI  - Maternal and fetal outcomes in placenta accreta after institution of team-managed
      care.
AB  - INTRODUCTION: Placenta accreta significantly contributes to maternal morbidity
      and mortality. We evaluated whether planned delivery and experienced, team
      managed surgical intervention results in improved outcomes. We also examined
      whether risk factors differed for accreta, increta, and percreta and evaluated
      whether excess lower segment uterine vascularity correlates with disease
      severity. METHODS: We retrospectively analyzed patients before versus after
      institution of a management protocol. Of the 58 044 deliveries over 10 years,
      there were 67 women whose pregnancies were histopathologically confirmed as
      placenta accreta, increta, or percreta (1/866). Clinical outcome measures were
      estimated blood loss (EBL), packed red blood cells (pRBCs) transfused, maternal
      and fetal complications, intensive care unit admission, and length of stay.
      RESULTS: There were no maternal or infant deaths. In the managed cohort, EBL was
      reduced by 48% (P < .001), intraoperative pRBCs transfused by 40% (P < .01),
      total transfused pRBCs per case by 50% (P < .01), and surgical intensive care
      unit admissions by >50% (P < .01). Assessment of maternal risk factors by
      diagnosis revealed marked differences between accreta versus increta and
      percreta. Clinically assessed excess vascularity of the lower uterine segment
      correlated with disease severity. The incidence of neonatal complications was
      similar in both cohorts. CONCLUSIONS: Targeted delivery at 34 weeks and team
      managed diagnosis, treatment, and care of patients with placenta accreta were
      associated with improved maternal, but not neonatal outcomes.

PMID- 24336677
TI  - First-trimester levels of pregnancy-associated plasma protein A2 (PAPP-A2) in the
      maternal circulation are elevated in pregnancies that subsequently develop
      preeclampsia.
AB  - Recent studies have consistently found pregnancy-associated plasma protein A2
      (PAPP-A2) to be upregulated in preeclamptic placentae at term. We tested whether
      first-trimester circulating PAPP-A2 levels differed between complicated and
      uncomplicated pregnancies. We measured maternal PAPP-A2 levels at 10 to 14 weeks
      of gestational age in 17 pregnancies resulting in small-for-gestational-age (SGA)
      infants, 6 which developed preeclampsia (PE), 1 which developed PE and resulted
      in an SGA infant, and 37 gestational age-matched controls. The concentration of
      the PAPP-A2 isoform corresponding to the full-length protein was significantly
      higher in pregnancies that developed PE (35 ng/mL) compared with those that did
      not (23 ng/mL; P < .044). In contrast, we found no difference in PAPP-A2 levels
      between pregnancies that did or did not result in an SGA infant. The upregulation
      of PAPP-A2 that has previously been observed in PE at term appears to begin early
      in pregnancy, well before the symptoms develop. 

PMID- 24336678
TI  - Increased expression of kindlin 2 in luteinized granulosa cells correlates with
      androgen receptor level in patients with polycystic ovary syndrome having
      hyperandrogenemia.
AB  - Hyperandrogenemia is the leading defect in patients with polycystic ovary
      syndrome (PCOS) and considered to be involved in the ovulation dysfunction of
      PCOS. During the process of ovulation, granulosa cells (GCs) undergo epithelial
      mesenchymal transition (EMT), and integrin-interacting protein kindlin 2 is a
      well-known regulator in EMT. Therefore, our objective here was to compare the
      expression levels of kindlin 2 in luteinized GCs between patients with PCOS and
      control women and the relationship between kindlin 2 and PCOS pathogenesis. In
      this study, kindlin 2 expression was significantly increased in luteinized GCs
      from patients with PCOS, and kindlin 2 could be induced by testosterone both in
      vitro and in vivo. Meanwhile, kindlin 2 was positively correlated with androgen
      receptor (AR) in PCOS GCs. Taken together, kindlin 2 may play a role in
      luteinized GCs, especially in the case of excess androgen. Further studies are
      required to assess the specific role of kindlin 2 in follicular development and
      PCOS pathogenesis. 

PMID- 24336680
TI  - Now you like me, now you don't: impact of labels on odor perception.
AB  - Past research has shown that odor perception can be affected by how we label
      odors. The aim of this study was to expand on previous work by investigating the
      impact of labels on edibility, pleasantness, and intensity ratings as well as on
      reaction times when detecting labeled odors. We tested 50 subjects. Five odorants
      were administered, each with a positive and a negative label. Participants had to
      detect odors as fast as possible and then rate their edibility, pleasantness, and
      intensity. Because of a lack of fit, only 4 of the initial 5 odorants were
      analyzed. All odorants presented with positive labels were rated as being more
      edible than when they were presented with negative labels. Specifically, the
      effect was also seen for the 2 nonfood odorants suggesting an unbiased effect.
      All odorants presented with positive labels were rated as being more pleasant
      than when they were presented with negative labels. Labels also modulated
      intensity ratings and reaction times for some odors. In summary, odor labels
      affect pleasantness ratings and edibility perception. Although labels appear to
      also influence intensity ratings and reaction times, this seems to be a more
      complex relationship that could be modulated by additional factors such as odor
      valence, label fit, and possibly the edibility attributed to an odor or a label. 

PMID- 24336681
TI  - Microfluidic platforms: a mainstream technology for the preparation of crystals.
AB  - Microfluidics is a multidisciplinary field of science based on the manipulation
      of fluids in sub-millimeter dimensions where the fundamental fluid physics
      changes dramatically when compared to macroscale fluid physical phenomena.
      Therefore, the conditions that microfluidic technologies offer are completely
      different from those of bulk set-ups, and thus they are very interesting for the
      study of crystallisation because diffusion, mixing and mass and heat transport
      are all finely controlled, and are easily modulated. This tutorial review is
      intended to give a broad and up-to-date overview of the distinct microfluidic
      approaches that have been employed so far for crystallisation studies for the
      uninitiated in these techniques. Main emphasis will be given to microfluidic
      platforms operating under continuous flow regimes, droplet-based methods, valve
      based approaches, well-based methods, and digital microfluidics. This tutorial
      does not intend to give detailed methodology, but rather provides illustrative
      examples which capture the attention of the reader and allow them to appreciate
      the unique features that microfluidic technologies can offer towards the study of
      different crystallisation processes. Indeed, crystallisation studies of different
      types of crystalline matter including organic, inorganic and metal-organic
      materials are presented. 

PMID- 24336682
TI  - Engineering new layered solids from exfoliated inorganics: a periodically
      alternating hydrotalcite-montmorillonite layered hybrid.
AB  - Two-dimensional (2D) nanosheets obtained by exfoliating inorganic layered
      crystals have emerged as a new class of materials with unique attributes. One of
      the critical challenges is to develop robust and versatile methods for creating
      new nanostructures from these 2D-nanosheets. Here we report the delamination of
      layered materials that belonging to two different classes--the cationic clay,
      montmorillonite, and the anionic clay, hydrotalcite--by intercalation of
      appropriate ionic surfactants followed by dispersion in a non-polar solvent. The
      solids are delaminated to single layers of atomic thickness with the ionic
      surfactants remaining tethered to the inorganic and consequently the nanosheets
      are electrically neutral. We then show that when dispersions of the two solids
      are mixed the exfoliated sheets self-assemble as a new layered solid with
      periodically alternating hydrotalcite and montmorillonite layers. The procedure
      outlined here is easily extended to other layered solids for creating new
      superstructures from 2D-nanosheets by self-assembly.

PMID- 24336683
TI  - Calciprotein particle (CPP): a true culprit of phosphorus woes?

PMID- 24336685
TI  - Methane storage in tea clathrates.
AB  - Methane can be stored in tea clathrates, that is kinetics of methane clathrate
      formation can be significantly accelerated (90% saturation uptake in 20 min) by
      ingredients (polyphenols and saponins) in tea infusions with a volumetric
      capacity of up to 172 v/v. 

PMID- 24336686
TI  - Isomeric thiophene-fused benzocarborane molecules--different lithium doping
      effect on the nonlinear optical property.
AB  - Recently, two isomeric thiophene-fused benzocarborane derivatives Tb1 and Tb2
      with different locations of sulfur atoms, labeled as 1, 4 and 6, 9 of the
      thiophene were synthesized by Morisaki (Chem.-Eur. J., 2012, 18, 11251-11257) and
      Barrere (Macromolecules, 2009, 42, 2981-2987), respectively. In the present work,
      natural bond orbital (NBO) analysis shows that after doping one lithium atom into
      the isomeric structures Tb1 and Tb2, the electrons transfer to different regions
      in Tb1 and Tb2. For Tb1-Li, the transferred electrons mainly locate at S1, C2,
      C3, and S4, but for Tb2-Li, the transferred electrons mainly locate at C2, C3,
      C7, and C8. Significantly, the charge distribution is a crucial factor
      influencing the static first hyperpolarizabilities for Tb1-Li and Tb2-Li.
      Furthermore, the betatot value of Tb1-Li is 6222 au, which is about 160 times
      larger than that of Tb1 (39 au). However, the betatot value of Tb2-Li (498 au) is
      only about 5 times larger than that of the corresponding Tb2 (91 au). It is our
      expectation that this work could provide useful information for the development
      of nonlinear optical materials based on carboranes. 

PMID- 24336687
TI  - Role of poly(vinylpyrrolidone) (PVP) and other sterically protecting polymers in
      selective stabilization of {111} and {100} facets in pentagonally twinned silver
      nanoparticles.
AB  - The role of PVP in the selective formation of pentagonally twinned silver
      nanoparticle morphologies and the corresponding selective facet stabilization is
      elucidated. Both for decahedral and pentagonal rod nanoparticles, PVP does not
      promote specific facet selection but is instrumental in colloidal stabilization
      and facet preservation through steric protection. 

PMID- 24336688
TI  - Modeling complex and multi-component food systems in molecular dynamics
      simulations on the example of chocolate conching.
AB  - Additional benefits of foods are an increasing factor in the consumer's purchase.
      To produce foods with the properties the consumer demands, understanding the
      micro- and nanostructure is becoming more important in food research today. We
      present molecular dynamics (MD) simulations as a tool to study complex and multi
      component food systems on the example of chocolate conching. The process of
      conching is chosen because of the interesting challenges it provides: the
      components (fats, emulsifiers and carbohydrates) contain diverse functional
      groups, are naturally fluctuating in their chemical composition, and have a high
      number of internal degrees of freedom. Further, slow diffusion in the non-aqueous
      medium is expected. All of these challenges are typical to food systems in
      general. Simulation results show the suitability of present force fields to
      correctly model the liquid and crystal density of cocoa butter and sucrose,
      respectively. Amphiphilic properties of emulsifiers are observed by micelle
      formation in water. For non-aqueous media, pulling simulations reveal high energy
      barriers for motion in the viscous cocoa butter. The work for detachment of an
      emulsifier from the sucrose crystal is calculated and matched with detachment of
      the head and tail groups separately. Hydrogen bonding is shown to be the dominant
      interaction between the emulsifier and the crystal surface. Thus, MD simulations
      are suited to model the interaction between the emulsifier and sugar crystal
      interface in non-aqueous media, revealing detailed information about the
      structuring and interactions on a molecular level. With interaction parameters
      being available for a wide variety of chemical groups, MD simulations are a
      valuable tool to understand complex and multi-component food systems in general.
      MD simulations provide a substantial benefit to researchers to verify their
      hypothesis in dynamic simulations with an atomistic resolution. Rapid rise of
      computational resources successively increases the complexity and the size of the
      systems that can be studied. 

PMID- 24336689
TI  - Protein micro- and nano-capsules for biomedical applications.
AB  - Micro- and nano-scale systems have emerged as important tools for developing
      clinically useful drug delivery systems. In this tutorial review, we discuss the
      exploitation of biomacromolecules for this purpose, focusing on proteins,
      polypeptides, nucleic acids and polysaccharides and mixtures thereof as potential
      building blocks for novel drug delivery systems. We focus on the mechanisms of
      formation of micro- and nano-scale protein-based capsules and shells, as well as
      on the functionalization of such structures for use in targeted delivery of
      bioactive materials. We summarise existing methods for protein-based capsule
      synthesis and functionalization and highlight future challenges and opportunities
      for delivery strategies based on biomacromolecules. 

PMID- 24336690
TI  - Facile preparation of an n-type reduced graphene oxide field effect transistor at
      room temperature.
AB  - We introduce a facile method to prepare an n-type reduced graphene oxide field
      effect transistor at room temperature via a typical Benkeser reduction using
      lithium and ethylenediamine. 

PMID- 24336691
TI  - Pain management strategies for thoracotomy and thoracic pain syndromes.
AB  - Pain after thoracic surgery can be severe and, in the acute phase, contribute to
      perioperative morbidity and mortality. Unfortunately, patients also incur a
      significant risk of chronic pain. Although there are guidelines for postoperative
      pain management in these patients, there is no widespread surgical or anesthetic
      "best practice." Here, we review the recent literature on techniques specific to
      perioperative pain control for thoracic patients, including medical management,
      neuraxial blockade, and other regional techniques, and suggest an algorithm for
      developing a multimodal pain management strategy. 

PMID- 24336692
TI  - Sensory-specific satiation with a pinched nose and eyes closed: testing the
      sensory modality specificity of satiation.
AB  - Sensory-specific satiation refers to the decrease in pleasantness derived from a
      consumed food relative to other unconsumed foods. In the current study, it was
      investigated to what extent sensory-specific satiation is modality specific. To
      this end, 80 female participants ate a preferred snack until full while wearing
      (or not wearing) a blindfold and/or a nose clip. Impaired vision should impede
      satiation for the appearance of the consumed test snack. Obstructing olfaction
      should undermine satiation for the smell of the test snack. Indeed, when vision
      was obstructed, hedonic ratings of specifically snack appearance did not decrease
      as much. When olfaction was blocked, the hedonic ratings for the flavor of the
      test snack did not show as much of a reduction. It is concluded that, to a
      degree, sensory-specific satiation is indeed modality specific. 

PMID- 24336693
TI  - Structural responses of cells to intracellular magnetic force induced by
      superparamagnetic iron oxide nanoparticles.
AB  - In this paper, we study the effects of intracellular force on human umbilical
      vein endothelial cells. We generated intracellular force on endothelial cells
      under different magnetic fields using the cell uptake of superparamagnetic iron
      oxide nanoparticles. Cell responses to intracellular force were observed using
      fluorescent microscopy. Our results indicated that nanoparticles were taken up by
      the cell by endocytosis and were deposited in lysosomes. Nanoparticles and
      lysosomes inside the cell could be relocated by the application of a magnetic
      force. The intracellular magnetic force could also be used to accelerate cell
      migration by adjusting the magnetic fields and giving the cell free culture
      space. No cytotoxicity of nanoparticles was found in our experiments. By
      comparing intracellular relocalization with migration of the whole cell, we
      obtained a better understanding of the self-defence mechanisms of cells based on
      their mechanical properties. Based on the promising mechanical properties and low
      cytotoxicity of our magnetic nanoparticles, their potential applications in
      cytomechanics and cell patterning are discussed. 

PMID- 24336694
TI  - A social skills and parental training intervention for disruptive boys reduces
      substance use behaviours in adolescence.

PMID- 24336695
TI  - A dose reduction/discontinuation strategy improves long-term recovery in people
      with remitted first-episode psychosis compared to maintenance therapy.

PMID- 24336696
TI  - Mutations in rpoB and fusA cause resistance to rifampicin and fusidic acid in
      methicillin-resistant Staphylococcus aureus strains from a tertiary hospital in
      Malaysia.
AB  - BACKGROUND: The prevalence of resistance to rifampicin and fusidic acid among
      Malaysian strains of methicillin-resistant Staphylococcus aureus (MRSA) is
      increasing. This study aimed to determine the mechanisms of rifampicin and
      fusidic acid resistance and the genetic diversity of MRSA strains from a
      Malaysian tertiary hospital. METHODS: Minimum inhibitory concentrations (MIC) for
      21 MRSA strains were determined by agar dilution test and Etest. The resistance
      genes, staphylococcal chromosome cassette mec (SCCmec) types, multilocus-sequence
      typing (MLST) types and spa types, were determined by PCR and DNA sequencing.
      RESULTS: MIC for rifampicin and fusidic acid resistance ranged from <1 to 8 ug/ml
      and from <1 to 256 ug/ml, respectively. A double mutation (484Arg/His and
      517Glu/Gln) in rpoB causes high rifampicin resistance while a mutational change
      (461Leu/Lys) in fusA was observed in seven strains highly resistant to fusidic
      acid. Five of the seven were also resistant to rifampicin (MIC 8 ug/ml) and
      carried a mutated rpoB gene (484Arg/His). No other acquired fusidic acid
      resistance gene (fusB, fusC or fusD) was detected. Most (14/21) of the strains
      belonged to clone ST239-III-t037. Three belonged to ST22-IV-t1378 and the
      remaining four to ST239-III-t2029, ST239-III-t421, ST1178-IV-t1107 and ST241-III
      t363, respectively. CONCLUSIONS: The study showed that both rifampicin and
      fusidic acid resistance was associated with mutational change in rpoB and fusA,
      respectively. All rifampicin-resistant strains were from the same clone ST239-III
      t037 whereas strains resistant to fusidic acid were genetically more diverse.

PMID- 24336697
TI  - Prematurity, intrauterine growth retardation and low birth weight: risk factors
      in a malaria-endemic area in southern Benin.
AB  - BACKGROUND: The aim of this study was to describe the contribution of prematurity
      and small for gestational age (SGA) to low birth weight (LBW) as well as to
      identify risk factors associated with preterm birth and SGA and to explore their
      impact on birth weight. METHODS: A cross-sectional study was carried out in
      southern Benin between June 2007 and July 2008. At delivery, women's
      characteristics and newborn's anthropometric measurements were collected.
      Gestational age was estimated using the Ballard method; SGA was defined using the
      William's reference curve. Analyses were performed by multiple logistic and
      linear regressions. RESULTS: In total, 526 mother-infant pairs were enrolled. LBW
      (<2500 g), prematurity (<37 weeks) and SGA accounted for 9.1%, 10.3% and 25.3% of
      the sample, respectively. Infant's male gender was associated with a lower risk
      of prematurity (p=0.03). Low maternal anthropometric status (p<0.001),
      primiparity (p=0.017) and infant's male gender (p=0.015) were associated with an
      increased risk of SGA. Only low maternal anthropometric status and primiparity
      were associated with an increased risk of LBW, and their effect on LBW was
      mediated by SGA. CONCLUSIONS: SGA was the main mechanism mediating the effect of
      risk factors on LBW. Maternal undernutrition (either short stature or low
      anthropometric status) was the most important of them.

PMID- 24336698
TI  - Long-term outcomes of common atrioventricular valve plasty in patients with
      functional single ventricle.
AB  - OBJECTIVES: Common atrioventricular valve (CAVV) regurgitation is widely known as
      a risk factor for mortality and Fontan completion in patients with functional
      single ventricle. Hence, we reviewed our surgical experience with CAVV plasty in
      Fontan candidates. METHODS: Staged Fontan strategy and extracardiac total
      cavopulmonary connection as Fontan modification were our principal approaches in
      1995. Since then, 38 consecutive Fontan candidates (21 males, median weight at
      operation was 7.0 kg and median age was 17 months old) underwent CAVV plasty.
      Right atrial isomerism was associated with 24 patients. The initial CAVV plasty
      was performed before inter-stage bidirectional Glenn (BDG) in 3 patients, at BDG
      in 23, before Fontan in 4 and during Fontan in 8. Since 1995, the modified
      Alfieri technique with a tailed, expanded, polytetrafluoroethylene tube as a
      bridging strip was the procedure for repair and 27 patients underwent the
      procedure. The mean follow-up period was 7.1 years (range 0-17 years). RESULTS:
      Actuarial survival and freedom from CAVV replacement rates at 1, 5 and 10 years
      were 81, 70 and 67% and 89, 85 and 75%, respectively. Seven patients ultimately
      underwent CAVV replacement with one death. Twenty-three of the 38 patients
      completed Fontan operation (61%). Association with total anomalous pulmonary
      venous connection (P= 0.01) and CAVV plasty before BDG (P= 0.05) were risk
      factors for mortality. CONCLUSIONS: CAVV plasty for patients with functional
      single ventricle is still challenging; however, the aggressive and repeated
      surgical intervention may contribute to provide better life-prognosis. The
      ventricular volume unloading effect of BDG without additional pulmonary blood
      flow or Fontan operation did not contribute to maintain CAVV function. Therefore,
      there would not be any hesitation for CAVV replacement to control CAVVR in the
      setting of systemic ventricular failure. Although the statistically significant
      therapeutic superiority of the modified Alfieri technique was not shown so far,
      further follow-up may reveal the advantage of this easy and simple technique.

PMID- 24336700
TI  - Chest wall reconstruction with MatrixRib system: avoiding pitfalls.
AB  - Reconstructions of the chest wall using commercially available artificial
      metallic rib systems are gaining in popularity. The MatrixRib system involves use
      of plates and screws to bridge any defect and provide support for the chest wall
      following resection. So far, there has been no publication focusing on describing
      the use of this new technology in a step-by-step approach. We describe our
      technique and discuss potential pitfalls and difficulties of using the system. 

PMID- 24336699
TI  - Incidence, severity and perioperative risk factors for atrial fibrillation
      following pulmonary resection.
AB  - OBJECTIVES: Postoperative atrial fibrillation (PAF) occurs commonly following
      pulmonary resection. Our aims were to quantify the incidence and severity of PAF
      using the Thoracic Morbidity & Mortality classification system, and identify risk
      factors for PAF. METHODS: All consecutive patients undergoing pulmonary resection
      at a single centre (January 2008 - April 2010) were enrolled. PAF was defined as
      postoperative, electrocardiographically documented and requiring initiation of
      pharmacological therapy. Univariate and multivariate analyses of risk factors
      associated with the development of PAF were conducted. RESULTS: The incidence of
      PAF was 11.8% (n = 43) of 363 pulmonary resections (open: n = 173; 47.7%; video
      assisted: n = 177; 48.8%; converted: n = 13; 3.6%): sublobar (n = 93; 25.6%),
      lobectomy (n = 237; 65.3%), bilobectomy (n = 7; 1.9%) and pneumonectomy (n = 24;
      6.6%). Twenty-eight cases (65.1%) were uncomplicated/transient, and 15 cases
      (34.9%) were complicated/persistent PAF, defined as lasting for >7 days (40.0%),
      requiring cardioversion (13.3%), vasopressors (33.3%), in-hospital use of
      anticoagulants (46.7%) and/or anticoagulants on discharge (26.7%). Patients with
      PAF had increased mean lengths of hospital stay (10.5 days vs 6.9 days; P =
      0.04). Peak onset of PAF occurred 2.5 (standard deviation (SD) +/- 1.3) days
      after pulmonary resection, lasting for 1.8 +/- 2.8 (mean, +/-SD) days.
      Multivariate analysis identified (relative risk; 95% confidence interval): age
      >=70 years (2.3; 1.1-5.1), history of angioplasty/stents/angina (4.0; 1.4-11.3),
      thoracotomy (3.6; 1.4-9.3), conversion to open thoracotomy (16.5; 2.2-124.0) and
      extent of surgery/stage (7.1; 1.0-49.4) as predictors of PAF. CONCLUSIONS: While
      the majority of PAF is uncomplicated and transient, one-third of cases lead to
      persistence or major intervention. Age, coronary artery disease and extent of
      surgery/stage increase the risk of PAF following pulmonary resection. Identifying
      patients with elevated risk may lead to targeted prophylaxis to reduce the
      incidence of PAF.

PMID- 24336701
TI  - Risk of proximal aortic dissection in patients with bicuspid aortic valve: how to
      address this controversy?
AB  - The risk of acute aortic events in patients with bicuspid aortic valve (BAV)
      disease is a controversial issue. The real risk of aortic dissection in patients
      with BAV disease is unknown. An indirect assessment of this risk, however, could
      be gained with a more detailed understanding of the pathogenesis of BAV
      aortopathy. There are two major issues that should be clarified before one
      addresses the question of aortic dissection risk in BAV patients. The first
      issue, when analysing the data from previous BAV cohorts, is to determine what
      stage of BAV disease was present in the described patient population. In
      particular, was the risk of aortic dissection in BAV patients determined before
      or after aortic valve replacement (AVR) surgery? The second issue to consider is
      the functional state of the pathological valve within the observed population. In
      particular, did patients predominantly suffer from BAV stenosis or BAV
      insufficiency? Unfortunately, the vast majority of published reports do not
      separate between the different BAV phenotypes, thereby complicating
      interpretation of the results. Considering these two important clinical variables
      (i.e. the stage of BAV disease and the functional phenotype), we herein aim to
      explain the inconsistency of the published data with regard to the risk of aortic
      dissection in patients with BAV disease. 

PMID- 24336705
TI  - Do short-term changes in white matter structure indicate learning-induced myelin
      plasticity?

PMID- 24336706
TI  - Different calcium sources control somatic versus dendritic SK channel activation
      during action potentials.
AB  - Small-conductance calcium-activated potassium (SK) channels play an important
      role in regulating neuronal excitability. While SK channels at the soma have long
      been known to contribute to the medium afterhyperpolarization (mAHP), recent
      evidence indicates they also regulate NMDA receptor activation in dendritic
      spines. Here we investigate the activation of SK channels in spines and dendrites
      of rat cortical pyramidal neurons during action potentials (APs), and compare
      this to SK channel activation at the soma. Using confocal calcium imaging, we
      demonstrate that the inhibition of SK channels with apamin results in a location
      dependent increase in calcium influx into dendrites and spines during
      backpropagating APs (average increase, ~40%). This effect was occluded by block
      of R-type voltage-dependent calcium channels (VDCCs), but not by inhibition of N-
      or P/Q-type VDCCs, or block of calcium release from intracellular stores. During
      these experiments, we noticed that the calcium indicator (Oregon Green BAPTA-1)
      blocked the mAHP. Subsequent experiments using low concentrations of EGTA (1 mm)
      produced the same result, suggesting that somatic SK channels are not tightly
      colocalized with their calcium source. Consistent with this idea, all known
      subtypes of VDCCs except R-type were calcium sources for the apamin-sensitive
      mAHP at the soma. We conclude that SK channels in spines and dendrites of
      cortical pyramidal neurons regulate calcium influx during backpropagating APs in
      a distance-dependent manner, and are tightly coupled to R-type VDCCs. In
      contrast, SK channels activated by APs at the soma of these neurons are weakly
      coupled to a variety of VDCCs.

PMID- 24336707
TI  - Diagnostic value underlies asymmetric updating of impressions in the morality and
      ability domains.
AB  - While positive behavioral information is diagnostic when evaluating a person's
      abilities, negative information is diagnostic when evaluating morality. Although
      social psychology has considered these two domains as orthogonal and distinct
      from one another, we demonstrate that this asymmetry in diagnosticity can be
      explained by a single parsimonious principle--the perceived frequency of
      behaviors in these domains. Less frequent behaviors (e.g., high ability and low
      morality) are weighed more heavily in evaluations. We show that this statistical
      principle of frequency-derived diagnosticity is evident in human participants at
      both behavioral and neural levels of analysis. Specifically, activity in right
      ventrolateral prefrontal cortex increased preferentially when participants
      updated impressions based on diagnostic behaviors, and further, activity in this
      region covaried parametrically with the perceived frequency of behaviors.
      Activity in left ventrolateral PFC, left inferior frontal gyrus, and left
      superior temporal sulcus showed similar patterns of diagnosticity and
      sensitivity, though additional analyses confirmed that these regions responded
      primarily to updates based on immoral behaviors.

PMID- 24336708
TI  - Mouse primary visual cortex is used to detect both orientation and contrast
      changes.
AB  - In mammals, the lateral geniculate nucleus (LGN) and the superior colliculus (SC)
      are the major targets of visual inputs from the retina. The LGN projects mainly
      to primary visual cortex (V1) while the SC targets the thalamus and brainstem,
      providing two potential pathways for processing visual inputs. Indeed, cortical
      lesion experiments in rodents have yielded mixed results, leading to the
      hypothesis that performance of simple visual behaviors may involve computations
      performed entirely by this subcortical pathway through the SC. However, these
      previous experiments have been limited by both their assays of behavioral
      performance and their use of lesions to change cortical activity. To determine
      the contribution of V1 to these tasks, we trained mice to perform threshold
      detection tasks in which they reported changes in either the contrast or
      orientation of visual stimuli. We then reversibly inhibited V1 by optogenetically
      activating parvalbumin-expressing inhibitory neurons with channelrhodopsin-2. We
      found that suppressing activity in V1 substantially impaired performance in
      visual detection tasks. The behavioral deficit depended on the retinotopic
      position of the visual stimulus, confirming that the effect was due to the
      specific suppression of the visually driven V1 neurons. Behavioral effects were
      seen with only moderate changes in neuronal activity, as inactivation that raised
      neuronal contrast thresholds by a median of only 14% was associated with a
      doubling of behavioral contrast detection threshold. Thus, detection of changes
      in either orientation or contrast is dependent on, and highly sensitive to, the
      activity of neurons in V1. 

PMID- 24336710
TI  - Internal and external influences on the rate of sensory evidence accumulation in
      the human brain.
AB  - We frequently need to make timely decisions based on sensory evidence that is
      weak, ambiguous, or noisy resulting from conditions in the external environment
      (e.g., a cluttered visual scene) or within the brain itself (e.g., inattention,
      neural noise). Here we examine how externally and internally driven variations in
      the quality of sensory evidence affect the build-to-threshold dynamics of a
      supramodal "decision variable" signal and, hence, the timing and accuracy of
      decision reports in humans. Observers performed a continuous-monitoring version
      of the prototypical two-alternative dot-motion discrimination task, which is
      known to strongly benefit from sequential sampling and temporal accumulation of
      evidence. A centroparietal positive potential (CPP), which we previously
      established as a supramodal decision signal based on its invariance to motor or
      sensory parameters, exhibited two key identifying properties associated with the
      "decision variable" long described in sequential sampling models: (1) its buildup
      rate systematically scaled with sensory evidence strength across four levels of
      motion coherence, consistent with temporal integration; and (2) its amplitude
      reached a stereotyped level at the moment of perceptual report executions,
      consistent with a boundary-crossing stopping criterion. The buildup rate of the
      CPP also strongly predicted reaction time within coherence levels (i.e.,
      independent of physical evidence strength), and this endogenous variation was
      linked with attentional fluctuations indexed by the level of parieto-occipital
      alpha-band activity preceding target onset. In tandem with the CPP, build-to
      threshold dynamics were also observed in an effector-selective motor preparation
      signal; however, the buildup of this motor-specific process significantly lagged
      that of the supramodal process. 

PMID- 24336709
TI  - Mechanisms of transthyretin inhibition of beta-amyloid aggregation in vitro.
AB  - Tissue-specific overexpression of the human systemic amyloid precursor
      transthyretin (TTR) ameliorates Alzheimer's disease (AD) phenotypes in APP23
      mice. TTR-beta-amyloid (Abeta) complexes have been isolated from APP23 and some
      human AD brains. We now show that substoichiometric concentrations of TTR
      tetramers suppress Abeta aggregation in vitro via an interaction between the
      thyroxine binding pocket of the TTR tetramer and Abeta residues 18-21 (nuclear
      magnetic resonance and epitope mapping). The K(D) is micromolar, and the
      stoichiometry is <1 for the interaction (isothermal titration calorimetry).
      Similar experiments show that engineered monomeric TTR, the best inhibitor of
      Abeta fibril formation in vitro, did not bind Abeta monomers in liquid phase,
      suggesting that inhibition of fibrillogenesis is mediated by TTR tetramer binding
      to Abeta monomer and both tetramer and monomer binding of Abeta oligomers. The
      thousand-fold greater concentration of tetramer relative to monomer in vivo makes
      it the likely suppressor of Abeta aggregation and disease in the APP23 mice.

PMID- 24336711
TI  - Loss of functional A-type potassium channels in the dendrites of CA1 pyramidal
      neurons from a mouse model of fragile X syndrome.
AB  - Despite the critical importance of voltage-gated ion channels in neurons, very
      little is known about their functional properties in Fragile X syndrome: the most
      common form of inherited cognitive impairment. Using three complementary
      approaches, we investigated the physiological role of A-type K(+) currents
      (I(KA)) in hippocampal CA1 pyramidal neurons from fmr1-/y mice. Direct
      measurement of I(KA) using cell-attached patch-clamp recordings revealed that
      there was significantly less I(KA) in the dendrites of CA1 neurons from fmr1-/y
      mice. Interestingly, the midpoint of activation for A-type K(+) channels was
      hyperpolarized for fmr1-/y neurons compared with wild-type, which might partially
      compensate for the lower current density. Because of the rapid time course for
      recovery from steady-state inactivation, the dendritic A-type K(+) current in CA1
      neurons from both wild-type and fmr1-/y mice is likely mediated by K(V)4
      containing channels. The net effect of the differences in I(KA) was that back
      propagating action potentials had larger amplitudes producing greater calcium
      influx in the distal dendrites of fmr1-/y neurons. Furthermore, CA1 pyramidal
      neurons from fmr1-/y mice had a lower threshold for LTP induction. These data
      suggest that loss of I(KA) in hippocampal neurons may contribute to dendritic
      pathophysiology in Fragile X syndrome.

PMID- 24336713
TI  - The Coffin-Lowry syndrome-associated protein RSK2 regulates neurite outgrowth
      through phosphorylation of phospholipase D1 (PLD1) and synthesis of phosphatidic
      acid.
AB  - More than 80 human X-linked genes have been associated with mental retardation
      and deficits in learning and memory. However, most of the identified mutations
      induce limited morphological alterations in brain organization and the molecular
      bases underlying neuronal clinical features remain elusive. We show here that
      neurons cultured from mice lacking ribosomal S6 kinase 2 (Rsk2), a model for the
      Coffin-Lowry syndrome (CLS), exhibit a significant delay in growth in a similar
      way to that shown by neurons cultured from phospholipase D1 (Pld1) knock-out
      mice. We found that gene silencing of Pld1 or Rsk2 as well as acute
      pharmacological inhibition of PLD1 or RSK2 in PC12 cells strongly impaired
      neuronal growth factor (NGF)-induced neurite outgrowth. Expression of a
      phosphomimetic PLD1 mutant rescued the inhibition of neurite outgrowth in PC12
      cells silenced for RSK2, revealing that PLD1 is a major target for RSK2 in
      neurite formation. NGF-triggered RSK2-dependent phosphorylation of PLD1 led to
      its activation and the synthesis of phosphatidic acid at sites of neurite growth.
      Additionally, total internal reflection fluorescence microscopy experiments
      revealed that RSK2 and PLD1 positively control fusion of tetanus neurotoxin
      insensitive vesicle-associated membrane protein (TiVAMP)/VAMP-7 vesicles at sites
      of neurite outgrowth. We propose that the loss of function mutations in RSK2 that
      leads to CLS and neuronal deficits are related to defects in neuronal growth due
      to impaired RSK2-dependent PLD1 activity resulting in a reduced vesicle fusion
      rate and membrane supply. 

PMID- 24336712
TI  - Cortical pitch regions in humans respond primarily to resolved harmonics and are
      located in specific tonotopic regions of anterior auditory cortex.
AB  - Pitch is a defining perceptual property of many real-world sounds, including
      music and speech. Classically, theories of pitch perception have differentiated
      between temporal and spectral cues. These cues are rendered distinct by the
      frequency resolution of the ear, such that some frequencies produce "resolved"
      peaks of excitation in the cochlea, whereas others are "unresolved," providing a
      pitch cue only via their temporal fluctuations. Despite longstanding interest,
      the neural structures that process pitch, and their relationship to these cues,
      have remained controversial. Here, using fMRI in humans, we report the following:
      (1) consistent with previous reports, all subjects exhibited pitch-sensitive
      cortical regions that responded substantially more to harmonic tones than
      frequency-matched noise; (2) the response of these regions was mainly driven by
      spectrally resolved harmonics, although they also exhibited a weak but consistent
      response to unresolved harmonics relative to noise; (3) the response of pitch
      sensitive regions to a parametric manipulation of resolvability tracked
      psychophysical discrimination thresholds for the same stimuli; and (4) pitch
      sensitive regions were localized to specific tonotopic regions of anterior
      auditory cortex, extending from a low-frequency region of primary auditory cortex
      into a more anterior and less frequency-selective region of nonprimary auditory
      cortex. These results demonstrate that cortical pitch responses are located in a
      stereotyped region of anterior auditory cortex and are predominantly driven by
      resolved frequency components in a way that mirrors behavior. 

PMID- 24336714
TI  - Motor axon regeneration and muscle reinnervation in young adult and aged animals.
AB  - Injuries to peripheral nerves can cause paralysis and sensory disturbances, but
      such functional impairments are often short lived because of efficient
      regeneration of damaged axons. The time required for functional recovery,
      however, increases with advancing age (Verdu et al., 2000; Kawabuchi et al.,
      2011). Incomplete or delayed recovery after peripheral nerve damage is a major
      health concern in the aging population because it can severely restrict a
      person's mobility and independence. A variety of possible causes have been
      suggested to explain why nervous systems in aged individuals recover more slowly
      from nerve damage. Potential causes include age-related declines in the
      regenerative potential of peripheral axons and decreases in the supply or
      responsivity to trophic and/or tropic factors. However, there have been few
      direct analyses of age-related axon regeneration. Our aim here was to observe
      axons directly in young and old mice as they regenerate and ultimately reoccupy
      denervated neuromuscular synaptic sites to learn what changes in this process are
      age related. We find that damaged nerves in aged animals clear debris more slowly
      than nerves in young animals and that the greater number of obstructions
      regenerating axons encounter in the endoneurial tubes of old animals give rise to
      slower regeneration. Surprisingly, however, axons from aged animals regenerate
      quickly when not confronted by debris and reoccupy neuromuscular junction sites
      efficiently. These results imply that facilitating clearance of axon debris might
      be a good target for the treatment of nerve injury in the aged. 

PMID- 24336715
TI  - Extinction of remotely acquired fear depends on an inhibitory NR2B/PKA pathway in
      the retrosplenial cortex.
AB  - As memories age, their processing increasingly relies upon cortical rather than
      hippocampal circuits, but the adaptive significance and mechanisms of this shift
      are not fully understood. Here we investigated the behavioral features and
      cortical mechanisms underlying extinction of remotely versus recently acquired
      context fear in mice. Behaviorally, extinction and reinstatement were similar,
      but re-extinction of remote fear was significantly faster, suggesting time
      dependent engagement of mechanisms specific for processing remote memory. Using
      pharmacological manipulations of NMDA receptors and associated signaling pathways
      in the in the retrosplenial cortex, we demonstrated that extinction of remote
      fear uniquely required NR2B-mediated downregulation of the cAMP-dependent protein
      kinase (PKA)/cAMP response element-binding protein pathway. Interestingly,
      NR2B/PKA interactions weakened independently of the age of the memory, but the
      functional significance of this molecular change was evident only as memory
      retrieval became PKA-dependent over time. Thus, cortical PKA signaling may
      provide a molecular signature of when a memory has become "remote," and
      inhibition of this pathway may open the door for modulation of remote memories. 

PMID- 24336716
TI  - Motor skill learning induces changes in white matter microstructure and
      myelination.
AB  - Learning a novel motor skill is associated with well characterized structural and
      functional plasticity in the rodent motor cortex. Furthermore, neuroimaging
      studies of visuomotor learning in humans have suggested that structural
      plasticity can occur in white matter (WM), but the biological basis for such
      changes is unclear. We assessed the influence of motor skill learning on WM
      structure within sensorimotor cortex using both diffusion MRI fractional
      anisotropy (FA) and quantitative immunohistochemistry. Seventy-two adult (male)
      rats were randomly assigned to one of three conditions (skilled reaching,
      unskilled reaching, and caged control). After 11 d of training, postmortem
      diffusion MRI revealed significantly higher FA in the skilled reaching group
      compared with the control groups, specifically in the WM subjacent to the
      sensorimotor cortex contralateral to the trained limb. In addition, within the
      skilled reaching group, FA across widespread regions of WM in the contralateral
      hemisphere correlated significantly with learning rate. Immunohistological
      analysis conducted on a subset of 24 animals (eight per group) revealed
      significantly increased myelin staining in the WM underlying motor cortex in the
      hemisphere contralateral (but not ipsilateral) to the trained limb for the
      skilled learning group versus the control groups. Within the trained hemisphere
      (but not the untrained hemisphere), myelin staining density correlated
      significantly with learning rate. Our results suggest that learning a novel motor
      skill induces structural change in task-relevant WM pathways and that these
      changes may in part reflect learning-related increases in myelination. 

PMID- 24336717
TI  - A tweaking principle for executive control: neuronal circuit mechanism for rule
      based task switching and conflict resolution.
AB  - A hallmark of executive control is the brain's agility to shift between different
      tasks depending on the behavioral rule currently in play. In this work, we
      propose a "tweaking hypothesis" for task switching: a weak rule signal provides a
      small bias that is dramatically amplified by reverberating attractor dynamics in
      neural circuits for stimulus categorization and action selection, leading to an
      all-or-none reconfiguration of sensory-motor mapping. Based on this principle, we
      developed a biologically realistic model with multiple modules for task
      switching. We found that the model quantitatively accounts for complex task
      switching behavior: switch cost, congruency effect, and task-response
      interaction; as well as monkey's single-neuron activity associated with task
      switching. The model yields several testable predictions, in particular, that
      category-selective neurons play a key role in resolving sensory-motor conflict.
      This work represents a neural circuit model for task switching and sheds insights
      in the brain mechanism of a fundamental cognitive capability. 

PMID- 24336718
TI  - Dendritic arborization and spine dynamics are abnormal in the mouse model of
      MECP2 duplication syndrome.
AB  - MECP2 duplication syndrome is a childhood neurological disorder characterized by
      intellectual disability, autism, motor abnormalities, and epilepsy. The disorder
      is caused by duplications spanning the gene encoding methyl-CpG-binding protein-2
      (MeCP2), a protein involved in the modulation of chromatin and gene expression.
      MeCP2 is thought to play a role in maintaining the structural integrity of
      neuronal circuits. Loss of MeCP2 function causes Rett syndrome and results in
      abnormal dendritic spine morphology and decreased pyramidal dendritic arbor
      complexity and spine density. The consequences of MeCP2 overexpression on
      dendritic pathophysiology remain unclear. We used in vivo two-photon microscopy
      to characterize layer 5 pyramidal neuron spine turnover and dendritic
      arborization as a function of age in transgenic mice expressing the human MECP2
      gene at twice the normal levels of MeCP2 (Tg1; Collins et al., 2004). We found
      that spine density in terminal dendritic branches is initially higher in young
      Tg1 mice but falls below control levels after postnatal week 12, approximately
      correlating with the onset of behavioral symptoms. Spontaneous spine turnover
      rates remain high in older Tg1 animals compared with controls, reflecting the
      persistence of an immature state. Both spine gain and loss rates are higher, with
      a net bias in favor of spine elimination. Apical dendritic arbors in both simple-
      and complex-tufted layer 5 Tg1 pyramidal neurons have more branches of higher
      order, indicating that MeCP2 overexpression induces dendritic overgrowth. P70S6K
      was hyperphosphorylated in Tg1 somatosensory cortex, suggesting that elevated
      mTOR signaling may underlie the observed increase in spine turnover and dendritic
      growth. 

PMID- 24336719
TI  - Dysfunctional astrocytic and synaptic regulation of hypothalamic glutamatergic
      transmission in a mouse model of early-life adversity: relevance to neurosteroids
      and programming of the stress response.
AB  - Adverse early-life experiences, such as poor maternal care, program an abnormal
      stress response that may involve an altered balance between excitatory and
      inhibitory signals. Here, we explored how early-life stress (ELS) affects
      excitatory and inhibitory transmission in corticotrophin-releasing factor (CRF)
      expressing dorsal-medial (mpd) neurons of the neonatal mouse hypothalamus. We
      report that ELS associates with enhanced excitatory glutamatergic transmission
      that is manifested as an increased frequency of synaptic events and increased
      extrasynaptic conductance, with the latter associated with dysfunctional
      astrocytic regulation of glutamate levels. The neurosteroid 5alpha-pregnan-3alpha
      ol-20-one (5alpha3alpha-THPROG) is an endogenous, positive modulator of GABAA
      receptors (GABAARs) that is abundant during brain development and rises rapidly
      during acute stress, thereby enhancing inhibition to curtail stress-induced
      activation of the hypothalamic-pituitary-adrenocortical axis. In control mpd
      neurons, 5alpha3alpha-THPROG potently suppressed neuronal discharge, but this
      action was greatly compromised by prior ELS exposure. This neurosteroid
      insensitivity did not primarily result from perturbations of GABAergic
      inhibition, but rather arose functionally from the increased excitatory drive
      onto mpd neurons. Previous reports indicated that mice (dams) lacking the GABAAR
      delta subunit (delta(0/0)) exhibit altered maternal behavior. Intriguingly,
      delta(0/0) offspring showed some hallmarks of abnormal maternal care that were
      further exacerbated by ELS. Moreover, in common with ELS, mpd neurons of
      delta(0/0) pups exhibited increased synaptic and extrasynaptic glutamatergic
      transmission and consequently a blunted neurosteroid suppression of neuronal
      firing. This study reveals that increased synaptic and tonic glutamatergic
      transmission may be a common maladaptation to ELS, leading to enhanced excitation
      of CRF-releasing neurons, and identifies neurosteroids as putative early
      regulators of the stress neurocircuitry. 

PMID- 24336720
TI  - Multimodal integration of self-motion cues in the vestibular system: active
      versus passive translations.
AB  - The ability to keep track of where we are going as we navigate through our
      environment requires knowledge of our ongoing location and orientation. In
      response to passively applied motion, the otolith organs of the vestibular system
      encode changes in the velocity and direction of linear self-motion (i.e.,
      heading). When self-motion is voluntarily generated, proprioceptive and motor
      efference copy information is also available to contribute to the brain's
      internal representation of current heading direction and speed. However to date,
      how the brain integrates these extra-vestibular cues with otolith signals during
      active linear self-motion remains unknown. Here, to address this question, we
      compared the responses of macaque vestibular neurons during active and passive
      translations. Single-unit recordings were made from a subgroup of neurons at the
      first central stage of sensory processing in the vestibular pathways involved in
      postural control and the computation of self-motion perception. Neurons responded
      far less robustly to otolith stimulation during self-generated than passive head
      translations. Yet, the mechanism underlying the marked cancellation of otolith
      signals did not affect other characteristics of neuronal responses (i.e.,
      baseline firing rate, tuning ratio, orientation of maximal sensitivity vector).
      Transiently applied perturbations during active motion further established that
      an otolith cancellation signal was only gated in conditions where proprioceptive
      sensory feedback matched the motor-based expectation. Together our results have
      important implications for understanding the brain's ability to ensure accurate
      postural and motor control, as well as perceptual stability, during active self
      motion. 

PMID- 24336721
TI  - Target-specific effects of somatostatin-expressing interneurons on neocortical
      visual processing.
AB  - A diverse array of interneuron types regulates activity in the mammalian
      neocortex. Two of the most abundant are the fast-spiking, parvalbumin-positive
      (PV(+)) interneurons, which target the axosomatic region of pyramidal cells, and
      the somatostatin-positive (SOM(+)) interneurons, which target the dendrites.
      Recent work has focused on the influence of PV(+) and SOM(+) interneurons on
      pyramidal cells. However, the connections among PV(+) and SOM(+) interneurons are
      poorly understood and could play an important role in cortical circuitry, since
      their interactions may alter the net influence on pyramidal cell output. We used
      an optogenetic approach to investigate the effect of SOM(+) interneurons on
      pyramidal cells and PV(+) interneurons during visual stimulation in mouse primary
      visual cortex. We find that SOM(+) interneuron activation suppresses PV(+) cell
      spiking at least twice as potently as pyramidal cell spiking during visual
      stimulation. This differential effect of SOM(+) cell stimulation is detectable
      even when only two to three SOM(+) cells are activated. Importantly, the
      remaining responses to oriented gratings in PV(+) cells are more orientation
      tuned and temporally modulated, suggesting that SOM(+) activity unmasks this
      tuning by suppressing untuned input. Our results highlight the importance of
      SOM(+) inhibition of PV(+) interneurons during sensory processing. This prominent
      competitive inhibition between interneuron types leads to a reconfiguration of
      inhibition along the somatodendritic axis of pyramidal cells, and enhances the
      orientation selectivity of PV(+) cells. 

PMID- 24336722
TI  - Progranulin deficiency promotes post-ischemic blood-brain barrier disruption.
AB  - Loss-of-function mutations of progranulin (PGRN) have been linked to
      frontotemporal dementia, but little is known about the effects of PGRN deficiency
      on the brain in health and disease. PGRN has been implicated in neurovascular
      development, inflammation, and Wnt signaling, a pathway involved in the formation
      of the blood-brain barrier (BBB). Because BBB alterations and inflammation
      contribute to ischemic brain injury, we examined the role of PGRN in the brain
      damage produced by ischemia-reperfusion. PGRN(+/-) and PGRN(-/-) mice underwent
      middle cerebral artery occlusion (MCAO) with monitoring of cerebral blood flow.
      Infarct volume and motor deficits were assessed 72 h later. Post-ischemic
      inflammation was examined by expression of inflammatory genes and flow cytometry.
      BBB structure and permeability were examined by electron microscopy (EM) and
      Evans blue (EB) extravasation, respectively. MCAO resulted in ~60% larger
      infarcts in PGRN(+/-) and PGRN(-/-) mice, an effect independent of hemodynamic
      factors or post-ischemic inflammation. Rather, massive hemorrhages and post
      ischemic BBB disruption were observed, unrelated to degradation of tight junction
      (TJ) proteins or matrix metalloproteinases (MMPs). By EM, TJ were 30-52% shorter,
      fewer, and less interlocking, suggesting a weaker seal between endothelial cells.
      Intracerebral injection of platelet-derived growth factor-CC (PDGF-CC), which
      increases BBB permeability, resulted in a more severe BBB breakdown in PGRN(+/-)
      and PGRN(-/-) than wild-type mice. We describe a previously unrecognized
      involvement of PGRN in the expression of key ultrastructural features of the BBB.
      Such a novel vasoprotective role of PGRN may contribute to brain dysfunction and
      damage in conditions associated with reduced PGRN function.

PMID- 24336723
TI  - Defects in synapse structure and function precede motor neuron degeneration in
      Drosophila models of FUS-related ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease
      that leads invariably to fatal paralysis associated with motor neuron
      degeneration and muscular atrophy. One gene associated with ALS encodes the
      DNA/RNA-binding protein Fused in Sarcoma (FUS). There now exist two Drosophila
      models of ALS. In one, human FUS with ALS-causing mutations is expressed in fly
      motor neurons; in the other, the gene cabeza (caz), the fly homolog of FUS, is
      ablated. These FUS-ALS flies exhibit larval locomotor defects indicative of
      neuromuscular dysfunction and early death. The locus and site of initiation of
      this neuromuscular dysfunction remain unclear. We show here that in FUS-ALS
      flies, motor neuron cell bodies fire action potentials that propagate along the
      axon and voltage-dependent inward and outward currents in the cell bodies are
      indistinguishable in wild-type and FUS-ALS motor neurons. In marked contrast, the
      amplitude of synaptic currents evoked in the postsynaptic muscle cell is
      decreased by >80% in FUS-ALS larvae. Furthermore, the frequency but not unitary
      amplitude of spontaneous miniature synaptic currents is decreased dramatically in
      FUS-ALS flies, consistent with a change in quantal content but not quantal size.
      Although standard confocal microscopic analysis of the larval neuromuscular
      junction reveals no gross abnormalities, superresolution stimulated emission
      depletion (STED) microscopy demonstrates that the presynaptic active zone protein
      bruchpilot is aberrantly organized in FUS-ALS larvae. The results are consistent
      with the idea that defects in presynaptic terminal structure and function
      precede, and may contribute to, the later motor neuron degeneration that is
      characteristic of ALS. 

PMID- 24336724
TI  - Essential thalamic contribution to slow waves of natural sleep.
AB  - Slow waves represent one of the prominent EEG signatures of non-rapid eye
      movement (non-REM) sleep and are thought to play an important role in the
      cellular and network plasticity that occurs during this behavioral state. These
      slow waves of natural sleep are currently considered to be exclusively generated
      by intrinsic and synaptic mechanisms within neocortical territories, although a
      role for the thalamus in this key physiological rhythm has been suggested but
      never demonstrated. Combining neuronal ensemble recordings, microdialysis, and
      optogenetics, here we show that the block of the thalamic output to the neocortex
      markedly (up to 50%) decreases the frequency of slow waves recorded during non
      REM sleep in freely moving, naturally sleeping-waking rats. A smaller volume of
      thalamic inactivation than during sleep is required for observing similar effects
      on EEG slow waves recorded during anesthesia, a condition in which both bursts
      and single action potentials of thalamocortical neurons are almost exclusively
      dependent on T-type calcium channels. Thalamic inactivation more strongly reduces
      spindles than slow waves during both anesthesia and natural sleep. Moreover,
      selective excitation of thalamocortical neurons strongly entrains EEG slow waves
      in a narrow frequency band (0.75-1.5 Hz) only when thalamic T-type calcium
      channels are functionally active. These results demonstrate that the thalamus
      finely tunes the frequency of slow waves during non-REM sleep and anesthesia, and
      thus provide the first conclusive evidence that a dynamic interplay of the
      neocortical and thalamic oscillators of slow waves is required for the full
      expression of this key physiological EEG rhythm. 

PMID- 24336725
TI  - Chronometric electrical stimulation of right inferior frontal cortex increases
      motor braking.
AB  - The right inferior frontal cortex (rIFC) is important for stopping responses.
      Recent research shows that it is also activated when response emission is slowed
      down when stopping is anticipated. This suggests that rIFC also functions as a
      goal-driven brake. Here, we investigated the causal role of rIFC in goal-driven
      braking by using computer-controlled, event-related (chronometric), direct
      electrical stimulation (DES). We compared the effects of rIFC stimulation on
      trials in which responses were made in the presence versus absence of a stopping
      goal ("Maybe Stop" [MS] vs "No Stop" [NS]). We show that DES of rIFC slowed down
      responses (compared with control-site stimulation) and that rIFC stimulation
      induced more slowing when motor braking was required (MS) compared with when it
      was not (NS). Our results strongly support a causal role of a rIFC-based network
      in inhibitory motor control. Importantly, the results extend this causal role
      beyond externally driven stopping to goal-driven inhibitory control, which is a
      richer model of human self-control. These results also provide the first
      demonstration of double-blind chronometric DES of human prefrontal cortex, and
      suggest that--in the case of rIFC--this could lead to augmentation of motor
      braking.

PMID- 24336726
TI  - The indirect role of fibroblast growth factor-8 in defining neurogenic niches of
      the olfactory/GnRH systems.
AB  - Bone morphogenic protein-4 (BMP4) and fibroblast growth factor-8 (FGF8) are
      thought to have opposite roles in defining epithelial versus neurogenic fate in
      the developing olfactory/vomeronasal system. In particular, FGF8 has been
      implicated in specification of olfactory and gonadotropin releasing hormone-1
      (GnRH) neurons, as well as in controlling olfactory stem cell survival. Using
      different knock-in mouse lines and Cre-lox-mediated lineage tracing, Fgf8
      expression and cell lineage was analyzed in the developing nose in relation to
      the expression of Bmp4 and its antagonist Noggin (Nog). FGF8 is expressed by
      cells that acquire an epidermal, respiratory cell fate and not by stem cells that
      acquire neuronal olfactory or vomeronasal cell fate. Ectodermal and mesenchymal
      sources of BMP4 control the expression of BMP/TGFbeta antagonist Nog, whereas
      mesenchymal sources of Nog define the neurogenic borders of the olfactory pit.
      Fgf8 hypomorph mouse models, Fgf8(neo/neo) and Fgf8(neo/null), displayed severe
      craniofacial defects together with overlapping defects in the olfactory pit
      including (1) lack of neuronal formation ventrally, where GnRH neurons normally
      form, and (2) altered expression of Bmp4 and Nog, with Nog ectopically expressed
      in the nasal mesenchyme and no longer defining the GnRH and vomeronasal
      neurogenic border. Together our data show that (1) FGF8 is not sufficient to
      induce ectodermal progenitors of the olfactory pit to acquire neural fate and (2)
      altered neurogenesis and lack of GnRH neuron specification after chronically
      reduced Fgf8 expression reflected dysgenesis of the nasal region and loss of a
      specific neurogenic permissive milieu that was defined by mesenchymal signals. 

PMID- 24336727
TI  - Cholinergic blockade reduces theta-gamma phase amplitude coupling and speed
      modulation of theta frequency consistent with behavioral effects on encoding.
AB  - Large-scale neural activation dynamics in the hippocampal-entorhinal circuit
      local field potential, observable as theta and gamma rhythms and coupling between
      these rhythms, is predictive of encoding success. Behavioral studies show that
      systemic administration of muscarinic acetylcholine receptor antagonists
      selectively impairs encoding, suggesting that they may also disrupt the coupling
      between the theta and gamma bands. Here, we tested the hypothesis that muscarinic
      antagonists selectively disrupt coupling between theta and gamma. Specifically,
      we characterized the effects of systemically administered scopolamine on movement
      induced theta and gamma rhythms recorded in the superficial layers of the medial
      entorhinal cortex (MEC) of freely moving rats. We report the novel result that
      gamma power at the peak of theta was most reduced following muscarinic blockade,
      significantly shifting the phase of maximal gamma power to occur at later phases
      of theta. We also characterize the existence of multiple distinct gamma bands in
      the superficial layers of the MEC. Further, we observed that theta frequency was
      significantly less modulated by movement speed following muscarinic blockade.
      Finally, the slope relating speed to theta frequency, a correlate of familiarity
      with a testing enclosure, increased significantly less between the preinjection
      and recovery trials when scopolamine was administered during the intervening
      injection session than when saline was administered, suggesting that scopolamine
      reduced encoding of the testing enclosure. These data are consistent with
      computational models suggesting that encoding and retrieval occur during the peak
      and trough of theta, respectively, and support the theory that acetylcholine
      regulates the balance between encoding versus retrieval. 

PMID- 24336728
TI  - Stimulus timing-dependent plasticity in dorsal cochlear nucleus is altered in
      tinnitus.
AB  - Tinnitus and cochlear damage have been associated with changes in somatosensory
      auditory integration and plasticity in the dorsal cochlear nucleus (DCN).
      Recently, we demonstrated in vivo that DCN bimodal plasticity is stimulus timing
      dependent, with Hebbian and anti-Hebbian timing rules that reflect in vitro spike
      timing-dependent plasticity. In this in vivo study, we assessed the stimulus
      timing dependence of bimodal plasticity in a tinnitus model. Guinea pigs were
      exposed to a narrowband noise that produced a temporary elevation of auditory
      brainstem response thresholds. A total of 60% of the guinea pigs developed
      tinnitus as indicated by gap-induced prepulse inhibition of the acoustic startle.
      After noise exposure and tinnitus induction, stimulus timing-dependent plasticity
      was measured by comparing responses to sound before and after paired
      somatosensory and auditory stimulation presented with varying intervals and
      orders. In comparison with Sham and noise-exposed animals that did not develop
      tinnitus, timing rules in verified tinnitus animals were more likely to be anti
      Hebbian and broader for those bimodal intervals in which the neural activity
      showed enhancement. Furthermore, units from exposed animals with tinnitus were
      more weakly suppressed than either Sham animals or exposed animals without
      tinnitus. The broadened timing rules in the enhancement phase in animals with
      tinnitus, and in the suppressive phase in exposed animals without tinnitus was in
      contrast to narrow, Hebbian-like timing rules in Sham animals. These findings
      implicate alterations in DCN bimodal spike timing-dependent plasticity as
      underlying mechanisms in tinnitus, opening the way for a therapeutic target. 

PMID- 24336729
TI  - Stress switches cannabinoid type-1 (CB1) receptor-dependent plasticity from LTD
      to LTP in the bed nucleus of the stria terminalis.
AB  - The bed nucleus of the stria terminalis (BNST) exerts a coordinated modulation of
      the psychoneuroendocrine responses to stress. However, how acute stress impacts
      on BNST in vivo plasticity is a crucial question that still remains unanswered.
      Here, neurons from the anterior portion of the BNST (aBNST) were recorded in vivo
      during and after stimulation of their medial prefrontal cortical (mPFC)
      afferents. In C57BL/6N mice, a 1 h restraint stress induced a switch from long
      term depression (LTD) to long-term potentiation (LTP) in the aBNST after a 10 Hz
      mPFC stimulation. This switch was independent from glucocorticoid receptor
      stimulation. Because the endocannabinoid system regulates aBNST activity, we next
      examined the role of cannabinoid type-1 receptors (CB1-Rs) in these changes.
      Mutant mice lacking CB1-Rs (CB1(-/-) mice) displayed a marked deficit in the
      ability to develop plasticity under control and stress conditions, compared with
      their wild-type littermates (CB1(+/+) mice). This difference was not accounted
      for by genetic differences in stress sensitivity, as revealed by Fos
      immunohistochemistry analyses. Local blockade of CB1-Rs in the aBNST and the use
      of mutant mice bearing a selective deletion of CB1-Rs in cortical glutamatergic
      neurons indicated that stress-elicited LTP involved CB1-Rs located on aBNST
      excitatory terminals. These results show that acute stress reverts LTD into LTP
      in the aBNST and that the endocannabinoid system plays a key role therein. 

PMID- 24336730
TI  - Epigenetic regulation of sensory axon regeneration after spinal cord injury.
AB  - Axon regeneration is hindered by a decline of intrinsic axon growth capability in
      mature neurons. Reversing this decline is associated with the induction of a
      large repertoire of regeneration-associated genes (RAGs), but the underlying
      regulatory mechanisms of the transcriptional changes are largely unknown. Here,
      we establish a correlation between diminished axon growth potential and histone 4
      (H4) hypoacetylation. When neurons are triggered into a growth state, as in the
      conditioning lesion paradigm, H4 acetylation is restored, and RAG transcription
      is initiated. We have identified a set of target genes of Smad1, a
      proregenerative transcription factor, in conditioned DRG neurons. We also show
      that, during the epigenetic reprogramming process, histone-modifying enzymes work
      together with Smad1 to facilitate transcriptional regulation of RAGs.
      Importantly, targeted pharmacological modulation of the activity of histone
      modifying enzymes, such as histone deacetylases, leads to induction of multiple
      RAGs and promotion of sensory axon regeneration in a mouse model of spinal cord
      injury. Our findings suggest epigenetic modulation as a potential therapeutic
      strategy to enhance axon regeneration. 

PMID- 24336731
TI  - Gamma synchrony predicts neuron-neuron correlations and correlations with motor
      behavior in extrastriate visual area MT.
AB  - Correlated variability of neuronal responses is an important factor in estimating
      sensory parameters from a population response. Large correlations among neurons
      reduce the effective size of a neural population and increase the variation of
      the estimates. They also allow the activity of one neuron to be informative about
      impending perceptual decisions or motor actions on single trials. In extrastriate
      visual area MT of the rhesus macaque, for example, some but not all neurons show
      nonzero "choice probabilities" for perceptual decisions or non-zero "MT-pursuit"
      correlations between the trial-by-trial variations in neural activity and smooth
      pursuit eye movements. To understand the functional implications of zero versus
      nonzero correlations between neural responses and impending perceptions or
      actions, we took advantage of prior observations that specific frequencies of
      local field potentials reflect the correlated activity of neurons. We found that
      the strength of the spike-field coherence of a neuron in the gamma-band frequency
      range is related to the size of its MT-pursuit correlations for eye direction, as
      well as to the size of the neuron-neuron correlations. Spike-field coherence
      predicts MT-pursuit correlations better for direction than for speed, perhaps
      because the topographic organization of direction preference in MT is more
      amenable to creating meaningful local field potentials. We suggest that the
      relationship between spiking and local-field potentials is stronger for neurons
      that have larger correlations with their neighbors; larger neuron-neuron
      correlations create stronger MT-pursuit correlations. Neurons that lack strong
      correlations with their neighbors also have weaker correlations with pursuit
      behavior, but still could drive pursuit strongly. 

PMID- 24336732
TI  - Early onset of ataxia in moonwalker mice is accompanied by complete ablation of
      type II unipolar brush cells and Purkinje cell dysfunction.
AB  - Transient receptor potential "canonical" cation channels (TRPC) are involved in
      many cellular activities, including neuronal synaptic transmission. These
      channels couple lipid metabolism, calcium homeostasis, and electrophysiological
      properties as they are calcium permeable and activated through the phospholipase
      C pathway and by diacylglycerol. The TRPC3 subunit is abundantly expressed in
      Purkinje cells (PCs), where it mediates slow metabotropic glutamate receptor
      mediated synaptic responses. Recently, it has been shown that heterozygous
      moonwalker mice, which are a model of cerebellar ataxia, carry a dominant gain-of
      function mutation (T635A) in the TRPC3 gene. This mutation leads to PC loss and
      dysmorphism, which have been suggested to cause the ataxia. However, the ataxic
      phenotype is present from a very early stage (before weaning), whereas PC loss
      does not appear until several months of age. Here we show that another class of
      cerebellar neurons, the type II unipolar brush cells (UBCs), express functional
      TRPC3 channels; intriguingly, these cells are ablated in moonwalker mice by 1
      month of age. Additionally, we show that in moonwalker mice, intrinsic
      excitability of PCs is altered as early as 3 weeks after birth. We suggest that
      this altered excitability and the TRPC3-mediated loss of type II UBCs may both
      contribute to the ataxic phenotype of these mice and that different calcium
      handling in PCs and type II UBCs may account for the dramatic differences in
      sensitivity to the moonwalker mutation between these cell types. 

PMID- 24336734
TI  - DNA methylation and methyl-binding proteins control differential gene expression
      in distinct cortical areas of macaque monkey.
AB  - Distinct anatomical regions of the neocortex subserve different sensory
      modalities and neuronal integration functions, but mechanisms for these regional
      specializations remain elusive. Involvement of epigenetic mechanisms for such
      specialization through the spatiotemporal regulation of gene expression is an
      intriguing possibility. Here we examined whether epigenetic mechanisms might play
      a role in the selective gene expression in the association areas (AAs) and the
      primary visual cortex (V1) in macaque neocortex. By analyzing the two types of
      area-selective gene promoters that we previously identified, we found a striking
      difference of DNA methylation between these promoters, i.e., hypermethylation in
      AA-selective gene promoters and hypomethylation in V1-selective ones. Methylation
      levels of promoters of each area-selective gene showed no areal difference, but a
      specific methyl-binding protein (MBD4) was enriched in the AAs, in correspondence
      with expression patterns of AA-selective genes. MBD4 expression was mainly
      observed in neurons. MBD4 specifically bound to and activated the AA-selective
      genes both in vitro and in vivo. Our results demonstrate that methylation in the
      promoters and specific methyl-binding proteins play an important role in the area
      selective gene expression profiles in the primate neocortex. 

PMID- 24336733
TI  - Coarse-scale biases for spirals and orientation in human visual cortex.
AB  - Multivariate decoding analyses are widely applied to functional magnetic
      resonance imaging (fMRI) data, but there is controversy over their
      interpretation. Orientation decoding in primary visual cortex (V1) reflects
      coarse-scale biases, including an over-representation of radial orientations. But
      fMRI responses to clockwise and counter-clockwise spirals can also be decoded.
      Because these stimuli are matched for radial orientation, while differing in
      local orientation, it has been argued that fine-scale columnar selectivity for
      orientation contributes to orientation decoding. We measured fMRI responses in
      human V1 to both oriented gratings and spirals. Responses to oriented gratings
      exhibited a complex topography, including a radial bias that was most pronounced
      in the peripheral representation, and a near-vertical bias that was most
      pronounced near the foveal representation. Responses to clockwise and counter
      clockwise spirals also exhibited coarse-scale organization, at the scale of
      entire visual quadrants. The preference of each voxel for clockwise or counter
      clockwise spirals was predicted from the preferences of that voxel for
      orientation and spatial position (i.e., within the retinotopic map). Our results
      demonstrate a bias for local stimulus orientation that has a coarse spatial
      scale, is robust across stimulus classes (spirals and gratings), and suffices to
      explain decoding from fMRI responses in V1. 

PMID- 24336737
TI  - Retraction: Zeng et al., Epigenetic enhancement of BDNF signaling rescues
      synaptic plasticity in aging.

PMID- 24336736
TI  - Development of GABA circuitry of fast-spiking basket interneurons in the medial
      prefrontal cortex of erbb4-mutant mice.
AB  - erbb4 is a susceptibility gene for schizophrenia and ErbB4 signals have been
      hypothesized to function in a number of cortical developmental processes
      (Silberberg et al., 2006; Mei and Xiong, 2008). Several recent studies show that
      the expression of ErbB4 is mainly restricted to GABAergic interneurons (Yau et
      al., 2003; Woo et al., 2007), specifically, to parvalbumin-positive (PV) fast
      spiking (FS) interneurons (Vullhorst et al., 2009; Fazzari et al., 2010), a large
      majority of which are PV FS basket cells (Kawaguchi, 1995; Taniguchi et al.,
      2013). However, in the medial prefrontal cortex (mPFC), a brain region that is
      closely associated with neuropsychiatric disorders including schizophrenia,
      little is known about the roles of ErbB4 signals during the development of
      GABAergic circuitry particularly that associated with PV FS basket cells. Here,
      using molecular genetics, biochemistry, and electrophysiology, we deleted ErbB4
      receptors in GABAergic forebrain neurons during the embryonic period and
      demonstrated that in the mouse mPFC, ErbB4 signals were dispensable for the
      development of GABAergic synapses by PV FS basket cells. Interestingly, they were
      required for the final maturation rather than the initial formation of
      glutamatergic synapses on PV FS basket cells. Furthermore, activity-dependent
      GABAergic PV FS pyramidal neuron transmission was decreased, whereas activity of
      pyramidal neurons was increased in KO mice. Together, these data indicate that
      ErbB4 signals contribute to the development of GABAergic circuitry associated
      with FS basket cells in component- and stage-dependent manners in the mPFC in
      vivo, and may suggest a mechanism for neuropsychiatric disorders including
      schizophrenia. 

PMID- 24336738
TI  - Protecting the triplet excited state in sterically congested platinum porphyrin.
AB  - Platinum tetrakis(2,4,6-triethylphenyl)porphyrin (Pt-1) was synthesized and its
      structural (X-ray), electrochemical and photophysical properties were fully
      characterized. Comparative studies of Pt-1 and its unsubstituted analog PtTPP
      show the effect of sterically congesting ortho-substituents on the dynamics of
      the triplet excited states. Lowered quenching rates by 3-4 times were observed
      for Pt-1vs. PtTPP in the presence of oxygen and perylene, and in concentration
      (self)-quenching experiments. 

PMID- 24336735
TI  - Altered structural and functional synaptic plasticity with motor skill learning
      in a mouse model of fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common inherited intellectual disability.
      FXS results from a mutation that causes silencing of the FMR1 gene, which encodes
      the fragile X mental retardation protein. Patients with FXS exhibit a range of
      neurological deficits, including motor skill deficits. Here, we have investigated
      motor skill learning and its synaptic correlates in the fmr1 knock-out (KO)
      mouse. We find that fmr1 KO mice have impaired motor skill learning of a forelimb
      reaching task, compared with their wild-type (WT) littermate controls.
      Electrophysiological recordings from the forelimb region of the primary motor
      cortex demonstrated reduced, training-induced synaptic strengthening in the
      trained hemisphere. Moreover, long-term potentiation (LTP) is impaired in the
      fmr1 KO mouse, and motor skill training does not occlude LTP as it does in the WT
      mice. Whereas motor skill training induces an increase of synaptic AMPA-type
      glutamate receptor subunit 1 (GluA1), there is a delay in GluA1 increase in the
      trained hemisphere of the fmr1 KO mice. Using transcranial in vivo multiphoton
      microscopy, we find that fmr1 KO mice have similar spine density but increased
      dendritic spine turnover compared with WT mice. Finally, we report that motor
      skill training-induced formation of dendritic spines is impaired in fmr1 KO mice.
      We conclude that FMRP plays a role in motor skill learning and that reduced
      functional and structural synaptic plasticity might underlie the behavioral
      deficit in the fmr1 KO mouse. 

PMID- 24336740
TI  - Phenolic compounds: their journey after intake.
AB  - Plant foods are rich in phenolic compounds (PCs) that display multifaceted
      bioactions in health promotion and disease prevention. To exert their
      bioactivity, they must be delivered to and absorbed in the gastrointestinal (GI)
      tract, transported in circulation, and reach the target tissues. During the
      journey from ingestion to target tissues and final excretion, PCs are subjected
      to modifications by many factors during their absorption, deposition, metabolism
      and excretion (ADME) and consequently their bioefficacy may be modified.
      Consistent with all nutrients in foods, PCs must first be released from the food
      matrix through mechanical, chemical, and enzymatic forces to facilitate
      absorption along the GI tract, particularly in the upper small intestine section.
      Further, glycosylation of PCs directs the route of their absorption with glycones
      being transported through active transportation and aglycones through passive
      diffusion. After enteral absorption, the majority of PCs are extensively
      transformed by the detoxification system in enterocytes and liver for excretion
      in bile, feces, and urine. The journey of PCs from consumption to excretion
      appears to be comparable to many synthetic medications, but with some
      dissimilarities in their fate and bioactivity after phase I and II metabolism.
      The overall bioavailability of PCs is determined mainly by chemical
      characteristics, bioaccessibility, and ADME. In this review, factors accounting
      for variation in PCs bioavailability are discussed because this information is
      crucial for validation of the health benefits of PCs and their mechanism of
      action. 

PMID- 24336741
TI  - Synthesis of a nanocomposite composed of reduced graphene oxide and gold
      nanoparticles.
AB  - We report a seeded-growth process that results in the adhesion of size-controlled
      gold (Au) nanoparticles (NPs) to the surface of reduced graphene oxide (rGO),
      leading to the formation of rGO-Au nanocomposites. The synthesis approach
      involves the utilization of Au molecular precursors (i.e., the seeds) bonded to
      oxygen functionalities which intrinsically exist on GO. Upon reduction of the Au
      precursors, surface deposition of Au NPs is ensured. It is found that the size of
      Au NPs is controlled via the variation of precursor concentration in the growth
      solution. The redox chemistry between GO and Au precursors causes the reduction
      of GO to rGO and the generation of Au NPs on the surface of rGO. Microscopic and
      spectroscopic measurements have been performed to provide evidence for the
      suggested redox chemistry. 

PMID- 24336743
TI  - Stokes emission in GdF3:Nd3+ nanoparticles for bioimaging probes.
AB  - There is increasing interest in rare earth (RE) doped nanoparticles (NPs) due to
      their sharp absorption and photoluminescence (PL) in the near infrared (NIR)
      spectral region. These NIR based nanoparticles (NPs) could allow biological
      imaging at substantial depths with enhanced contrast and high spatial resolution
      due to the absence of auto fluorescence in biological samples under infrared
      excitation. Here, we present the highly efficient infrared photoluminescence in
      GdF3:Nd(3+) nanoparticles under 800 nm excitation within the hydrodynamic size
      limitations for bio-applications. The downconversion (Stokes emission) absolute
      quantum yields (QY) in powder, polymaleic anhydride-alt-1-octadicene (PMAO)
      coated powder and colloidal solutions have been investigated. QY measurements
      have revealed that downconversion (Stokes emission) QYs of approximately 5 +/- 2
      nm sized GdF3:1% Nd(3+) colloidal NPs are 2000 times higher than those of
      efficient upconversion (UC) particles NaYF4:20% Er/2% Yb of the same size.
      Furthermore, the utility of these NIR emitting nanoparticles for bioimaging
      probes has been demonstrated by confocal imaging and spectroscopic study.

PMID- 24336744
TI  - SGP-2, an acidic polysaccharide from Sarcandra glabra, inhibits proliferation and
      migration of human osteosarcoma cells.
AB  - An acidic polysaccharide (SGP-2), with a molecular weight of 1880 kDa, was
      purified from the defatted whole-plant of Sarcandra glabra (Thunb.) Nakai. SGP-2
      is mainly composed of glucose, galactose, mannose, arabinose and galacturonic
      acid in a molar ratio of 12.19 : 8.68 : 6.03 : 1.00 : 15.24. The primary
      structure analysis reveals that SGP-2 consists of 1,4-linked alpha-D-galacturonic
      acid, methyl-esterified 1,4-linked alpha-D-galacturonic acid, 1,5-linked alpha-L
      arabinose, 1,4-linked alpha-D-mannose, 1,6-linked beta-D-glucose and 1,3-linked
      beta-D-galactose with branch chains of 1,4,6-linked beta-D-glucose, 1,3,6-linked
      alpha-D-mannose and 1,4,6-linked alpha-D-galactose. The results of a cell
      viability assay and colony formation assay indicate that SGP-2 has a potent anti
      proliferation activity on human osteosarcoma MG-63 cells. SGP-2 increases the
      proportion of apoptotic cells and activates caspase-3. In addition, the anti
      proliferation effect induced by SGP-2 is blocked by the pan-caspase inhibitor.
      Moreover, SGP-2 inhibits the migratory capacity of MG-63 cells accompanied with
      the inhibition of receptor for advanced glycation end-products (RAGE) and nuclear
      factor-kappa B (NF-kappaB). Taken together, these results suggest that SGP-2 has
      anti-cancer potential in the treatment of human osteosarcoma.

PMID- 24336745
TI  - Low bone mineral density is related to high physiological levels of free
      thyroxine in peri-menopausal women.
AB  - OBJECTIVE: To determine whether thyroid hormone (free thyroxine (fT4)) rather
      than TSH is directly related to bone mineral density (BMD). DESIGN: Cross
      sectional population cohort study of peri-menopausal women. METHODS: Of a sample
      of 6846 peri-menopausal Dutch women who participated in an osteoporosis-screening
      programme, a cohort of 2584 was randomly selected for the assessment of thyroid
      function (TSH, fT4 and thyroid peroxidase antibodies (TPO-Abs)). TPO-Ab-positive
      women, with a previous history of thyroid dysfunction, overt thyroid disease,
      subclinical hypothyroidism, osteoporosis or bilateral oophorectomy and those
      receiving thyroid hormone or hormone replacement therapy were excluded. Of 1477
      eligible women, 1426 had TSH and fT4 within the reference range and 51 had low or
      undetectable serum TSH. BMD was measured at the lumbar spine and low BMD was
      defined as <0.937 g/cm(2). RESULTS: The mean BMD in the 51 women with low or
      undetectable serum TSH was 0.984 g/cm(2) compared with 1.001 g/cm(2) in the
      remaining 1426 (t=0.94, P=0.35); 33% of women with low or undetectable serum TSH
      had low BMD compared with 34% in 1426 euthyroid women. High fT4 but not low TSH
      in euthyroid women was related to low BMD by multiple logistic regression
      corrected for age, BMI and smoking (OR, 1.30; 95% CI, 1.02-1.69). CONCLUSIONS:
      Higher fT4 levels within the normal reference range but not low or undetectable
      serum TSH were independently related to decreased BMD at lumbar spine in peri
      menopausal women.

PMID- 24336746
TI  - Intergenic transcriptional interference is blocked by RNA polymerase III
      transcription factor TFIIIB in Saccharomyces cerevisiae.
AB  - The major function of eukaryotic RNA polymerase III is to transcribe transfer
      RNA, 5S ribosomal RNA, and other small non-protein-coding RNA molecules. Assembly
      of the RNA polymerase III complex on chromosomal DNA requires the sequential
      binding of transcription factor complexes TFIIIC and TFIIIB. Recent evidence has
      suggested that in addition to producing RNA transcripts, chromatin-assembled RNA
      polymerase III complexes may mediate additional nuclear functions that include
      chromatin boundary, nucleosome phasing, and general genome organization
      activities. This study provides evidence of another such "extratranscriptional"
      activity of assembled RNA polymerase III complexes, which is the ability to block
      progression of intergenic RNA polymerase II transcription. We demonstrate that
      the RNA polymerase III complex bound to the tRNA gene upstream of the
      Saccharomyces cerevisiae ATG31 gene protects the ATG31 promoter against
      readthrough transcriptional interference from the upstream noncoding intergenic
      SUT467 transcription unit. This protection is predominately mediated by binding
      of the TFIIIB complex. When TFIIIB binding to this tRNA gene is weakened, an
      extended SUT467-ATG31 readthrough transcript is produced, resulting in
      compromised ATG31 translation. Since the ATG31 gene product is required for
      autophagy, strains expressing the readthrough transcript exhibit defective
      autophagy induction and reduced fitness under autophagy-inducing nitrogen
      starvation conditions. Given the recent discovery of widespread pervasive
      transcription in all forms of life, protection of neighboring genes from
      intergenic transcriptional interference may be a key extratranscriptional
      function of assembled RNA polymerase III complexes and possibly other DNA binding
      proteins. 

PMID- 24336747
TI  - The novel zinc finger protein dASCIZ regulates mitosis in Drosophila via an
      essential role in dynein light-chain expression.
AB  - The essential zinc finger protein ASCIZ (also known as ATMIN, ZNF822) plays
      critical roles during lung organogenesis and B cell development in mice, where it
      regulates the expression of dynein light chain (DYNLL1/LC8), but its functions in
      other species including invertebrates are largely unknown. Here we report the
      identification of the Drosophila ortholog of ASCIZ (dASCIZ) and show that loss of
      dASCIZ function leads to pronounced mitotic delays with centrosome and spindle
      positioning defects during development, reminiscent of impaired dynein motor
      functions. Interestingly, similar mitotic and developmental defects were observed
      upon knockdown of the DYNLL/LC8-type dynein light chain Cutup (Ctp), and dASCIZ
      loss-of-function phenotypes could be suppressed by ectopic Ctp expression.
      Consistent with a genetic function of dASCIZ upstream of Ctp, we show that loss
      of dASCIZ led to reduced endogenous Ctp mRNA and protein levels and dramatically
      reduced Ctp-LacZ reporter gene activity in vivo, indicating that dASCIZ regulates
      development and mitosis as a Ctp transcription factor. We speculate that the more
      severe mitotic defects in the absence of ASCIZ in flies compared to mice may be
      due to redundancy with a second, ASCIZ-independent, Dynll2 gene in mammals in
      contrast to a single Ctp gene in Drosophila. Altogether, our data demonstrate
      that ASCIZ is an evolutionary highly conserved transcriptional regulator of
      dynein light-chain levels and a novel regulator of mitosis in flies. 

PMID- 24336748
TI  - Genome destabilizing mutator alleles drive specific mutational trajectories in
      Saccharomyces cerevisiae.
AB  - In addition to environmental factors and intrinsic variations in base
      substitution rates, specific genome-destabilizing mutations can shape the
      mutational trajectory of genomes. How specific alleles influence the nature and
      position of accumulated mutations in a genomic context is largely unknown.
      Understanding the impact of genome-destabilizing alleles is particularly relevant
      to cancer genomes where biased mutational signatures are identifiable. We first
      created a more complete picture of cellular pathways that impact mutation rate
      using a primary screen to identify essential Saccharomyces cerevisiae gene
      mutations that cause mutator phenotypes. Drawing primarily on new alleles
      identified in this resource, we measure the impact of diverse mutator alleles on
      mutation patterns directly by whole-genome sequencing of 68 mutation-accumulation
      strains derived from wild-type and 11 parental mutator genotypes. The accumulated
      mutations differ across mutator strains, displaying base-substitution biases,
      allele-specific mutation hotspots, and break-associated mutation clustering. For
      example, in mutants of POLalpha and the Cdc13-Stn1-Ten1 complex, we find a
      distinct subtelomeric bias for mutations that we show is independent of the
      target sequence. Together our data suggest that specific genome-instability
      mutations are sufficient to drive discrete mutational signatures, some of which
      share properties with mutation patterns seen in tumors. Thus, in a population of
      cells, genome-instability mutations could influence clonal evolution by
      establishing discrete mutational trajectories for genomes. 

PMID- 24336749
TI  - Gene duplication, lineage-specific expansion, and subfunctionalization in the
      MADF-BESS family patterns the Drosophila wing hinge.
AB  - Gene duplication, expansion, and subsequent diversification are features of the
      evolutionary process. Duplicated genes can be lost, modified, or altered to
      generate novel functions over evolutionary timescales. These features make gene
      duplication a powerful engine of evolutionary change. In this study, we explore
      these features in the MADF-BESS family of transcriptional regulators. In
      Drosophila melanogaster, the family contains 16 similar members, each containing
      an N-terminal, DNA-binding MADF domain and a C-terminal, protein-interacting,
      BESS domain. Phylogenetic analysis shows that members of the MADF-BESS family are
      expanded in the Drosophila lineage. Three members, which we name hinge1, hinge2,
      and hinge3 are required for wing development, with a critical role in the wing
      hinge. hinge1 is a negative regulator of Winglesss expression and interacts with
      core wing-hinge patterning genes such as teashirt, homothorax, and jing. Double
      knockdowns along with heterologous rescue experiments are used to demonstrate
      that members of the MADF-BESS family retain function in the wing hinge, in spite
      of expansion and diversification for over 40 million years. The wing hinge
      connects the blade to the thorax and has critical roles in fluttering during
      flight. MADF-BESS family genes appear to retain redundant functions to shape and
      form elements of the wing hinge in a robust and fail-safe manner. 

PMID- 24336750
TI  - Feedback regulation of SIN by Etd1 and Rho1 in fission yeast.
AB  - In fission yeast, the septation initiation network (SIN) is thought to promote
      cytokinesis by downstream activation of Rho1, a conserved GTPase that controls
      cell growth and division. Here we show that Etd1 and PP2A-Pab1, antagonistic
      regulators of SIN, are Rho1 regulators. Our genetic and biochemical studies
      indicate that a C-terminal region of Etd1 may activate Rho1 by directly binding
      it, whereas an N-terminal domain confers its ability to localize at the growing
      tips and the division site where Rho1 functions. In opposition to Etd1, our
      results indicate that PP2A-Pab1 inhibits Rho1. The SIN cascade is upstream
      regulated by the Spg1 GTPase. In the absence of Etd1, activity of Spg1 drops down
      prematurely, thereby inactivating SIN. Interestingly, we find that ectopic
      activation of Rho1 restores Spg1 activity in Etd1-depleted cells. By using a
      cytokinesis block strategy, we show that Rho1 is essential to feedback-activate
      Spg1 during actomyosin ring constriction. Therefore, activation of Spg1 by Rho1,
      which in turn is regulated by Etd1, uncovers a novel feedback loop mechanism that
      ensures SIN activity while cytokinesis is progressing. 

PMID- 24336751
TI  - An age-of-allele test of neutrality for transposable element insertions.
AB  - How natural selection acts to limit the proliferation of transposable elements
      (TEs) in genomes has been of interest to evolutionary biologists for many years.
      To describe TE dynamics in populations, previous studies have used models of
      transposition-selection equilibrium that assume a constant rate of transposition.
      However, since TE invasions are known to happen in bursts through time, this
      assumption may not be reasonable. Here we propose a test of neutrality for TE
      insertions that does not rely on the assumption of a constant transposition rate.
      We consider the case of TE insertions that have been ascertained from a single
      haploid reference genome sequence. By conditioning on the age of an individual TE
      insertion allele (inferred by the number of unique substitutions that have
      occurred within the particular TE sequence since insertion), we determine the
      probability distribution of the insertion allele frequency in a population sample
      under neutrality. Taking models of varying population size into account, we then
      evaluate predictions of our model against allele frequency data from 190
      retrotransposon insertions sampled from North American and African populations of
      Drosophila melanogaster. Using this nonequilibrium neutral model, we are able to
      explain ~ 80% of the variance in TE insertion allele frequencies based on age
      alone. Controlling for both nonequilibrium dynamics of transposition and host
      demography, we provide evidence for negative selection acting against most TEs as
      well as for positive selection acting on a small subset of TEs. Our work
      establishes a new framework for the analysis of the evolutionary forces governing
      large insertion mutations like TEs, gene duplications, or other copy number
      variants.

PMID- 24336752
TI  - Children of mothers with iodine deficiency during pregnancy are more likely to
      have lower verbal IQ and reading scores at 8-9 years of age.

PMID- 24336753
TI  - Parents of British Bangladeshi children undergoing cancer treatment report
      managing competing knowledge, vigilance, advocacy, balancing work and treatment
      burden impacts on their lives.

PMID- 24336754
TI  - A new air-stable zinc complex based on a 1,2-phenylene-diimino-2-cyanoacrylate
      ligand as an efficient catalyst of the epoxide-CO2 coupling.
AB  - A novel zinc complex based on a diethyl 1,2-phenylene-diimino-2-cyanoacrylate
      ligand is a very efficient catalyst in the conversion of epoxides with CO2 to
      organic carbonates, in the case of propylene carbonate also under mild reaction
      conditions. Using cyclohexene oxide leads to the formation of alternating
      aliphatic polycarbonates in good yields. 

PMID- 24336756
TI  - Rituximab as successful adjunct treatment in a patient with disseminated
      nontuberculous mycobacterial infection due to acquired anti-interferon-gamma
      autoantibody.
AB  - An acquired immune deficiency due to interferon gamma (IFN-gamma) autoantibodies
      was diagnosed in a 78-year-old Japanese man with treatment-refractory
      disseminated nontuberculous mycobacterial infection. In addition to standard
      antimycobacterial therapy, he was successfully treated with rituximab to
      eliminate B cells and thereby the autoantibody. Subsequently, he obtained a
      sustained remission from infection. 

PMID- 24336758
TI  - A novel macromolecular extract screened from satsuma with pro-inflammatory
      effect.
AB  - Excessive consumption of horticultural fruit is a double-edged sword with both
      positive and negative effects. In Eastern countries, a large number of people
      have suffered from shang huo as a result of excessive consumption of "heating"
      foods, such as lychee, longan, mandarin orange, mango and civet durian. The
      present study adopted a step by step strategy screened the compositions with pro
      inflammatory effect in satsuma fruits. The pro-inflammatory effects of all
      fractions were evaluated in RAW 264.7 cell lines by enzyme-linked immunosorbent
      assay (ELISA) and RT-PCR tests. The soluble water extract (SWE) from satsuma
      increased the production of prostaglandin E2 (PGE2) and promoted the expression
      level of cyclooxygenase-2 (COX-2) mRNA. SWE and high molecular weight molecules
      extracted from soluble water extract (HSWE) were respectively fractionated by
      dialysis bags and gel filtration chromatography. The macromolecular fraction
      named F1 was further obtained from HSWE, and could increase the production of
      inflammatory mediators. Finally F1 was resolved by SDS-PAGE and six proteins were
      identified by mass spectrometry. Compared with other detected proteins,
      polygalacturonase inhibitor (PGIP) and chitinase were the most likely candidate
      pro-inflammatory proteins according to molecular mass, and both of them were
      Citrus unshiu species. cDNA sequences of PGIP and chitinase were cloned and their
      functions were predicted as defensive proteins by SMART analysis. Excessive
      intake of these defensive proteins may result in adverse food reactions in human
      beings, such as shang huo and other immune responses. 

PMID- 24336757
TI  - Lipoprotein-associated phospholipase A2, a novel cardiovascular inflammatory
      marker, in HIV-infected patients.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging
      biomarker of cardiovascular disease. This study was conducted to describe the
      distribution of Lp-PLA2 in a cohort of human immunodeficiency virus (HIV)
      infected adults and to determine associations between Lp-PLA2, cardiometabolic
      risk factors, and subclinical atherosclerosis in this population. METHODS: Lp
      PLA2 was assessed in 341 (25% women, 52% white, 74% on highly active
      antiretroviral therapy [HAART]) participants of a cohort with detailed
      characterization of atherogenic risk factors, including surrogate markers of
      carotid and coronary atherosclerosis. RESULTS: Mean Lp-PLA2 mass was 313 +/- 105
      ng/mL and activity 173 +/- 49 nmol/minute/mL. Seventy-five percent of
      participants had abnormal Lp-PLA2. Those in the highest Framingham Risk Score
      tertile had significantly higher Lp-PLA2 activity. Participants with abnormal
      carotid intima-media thickness (cIMT) had higher Lp-PLA2 mass and activity. Those
      with coronary artery calcium (CAC) scores >100 had significantly higher Lp-PLA2
      mass than those with lower or nondetectable calcium. Those on HAART and protease
      inhibitor (PI)-based treatment had significantly higher Lp-PLA2 mass and activity
      than those who were treatment-naive or not on PIs. In multivariate regression,
      HAART and PI use were positively associated with Lp-PLA2 activity and mass after
      adjusting for age, race, sex, low-density and high-density lipoprotein
      cholesterol levels, triglyceride level, and smoking. Adding Lp-PLA2 activity
      tertiles to the model improved the predictive value for abnormal common cIMT, but
      not internal cIMT or CAC score. CONCLUSIONS: Lp-PLA2 is highly abnormal in HIV
      infected patients and is associated with several cardiovascular and HIV treatment
      specific risk factors. Lp-PLA2 may be used as an additional and more vascular
      specific biomarker for cardiovascular risk stratification in HIV-positive
      patients.

PMID- 24336759
TI  - An individually addressable suspended-drop electroporation system for high
      throughput cell transfection.
AB  - High-efficiency transfection of genes, proteins, or drug compounds into cells
      without causing permanent damage is a prerequisite for many cell biology
      experiments. Here, we report a printed circuit board (PCB)-based electroporation
      device for high-throughput delivery of exogenous molecules into cells in an
      individually addressable manner. This device incorporates an array of 96 through
      holes on the PCB with a pair of gold coated symmetric electrodes plated on the
      wall of each through-hole. A mixture of cell suspension and exogenous molecules
      is top-loaded, electroporated, and bottom-ejected with cell culture medium into
      the corresponding well of a 96-well plate placed under the PCB. One group of
      electrodes on the same side of the 96 through-holes were connected to eight top
      pads via connecting row wires plated on the top surface of the PCB and the other
      group of electrodes were connected in a column format to twelve bottom pads.
      Therefore, each pair of electrodes can be selectively energized, guaranteeing
      that appropriate electroporation parameters can be applied to different holes. We
      demonstrate the use of the present device to effectively introduce plasmid DNA
      and synthetic interfering RNA into cultured and primary cells with high cell
      viability and transfection efficiency. The high performance and low cost features
      make our device an ideal platform for cellular and molecular research and high
      throughput screening. 

PMID- 24336761
TI  - Serological evidence of infection of dogs with human influenza viruses in Japan.

PMID- 24336762
TI  - Internal and external parasitic infections in captive psittacine birds.

PMID- 24336763
TI  - First isolation of "Brachyspira hampsonii" from pigs in Europe.

PMID- 24336764
TI  - Continuous flow actuation between external reservoirs in small-scale devices
      driven by surface acoustic waves.
AB  - We have designed and characterized a surface acoustic wave (SAW) fluid actuation
      platform that significantly improves the transmission of sound energy from the
      SAW device into the fluid in order to obtain enhanced performance. This is in
      distinct contrast to previous SAW microfluidic devices where the SAW substrate is
      simply interfaced with a microchannel without due consideration given to the
      direction in which the sound energy is transmitted into the fluid, thus resulting
      in considerable reflective and dissipative losses due to reflection and
      absorption at the channel walls. For the first time, we therefore demonstrate the
      ability for continuous fluid transfer between independent reservoirs driven by
      the SAW in a miniature device and report the associated pressure-flow rate
      relationship, in which a maximum flow rate of 100 MUl min(-1) and pressure of 15
      Pa were obtained. The pumping efficiency is observed to increase with input power
      and, at peak performance, offers an order-of-magnitude improvement over that of
      existing SAW micropumps that have been reported to date. 

PMID- 24336766
TI  - Empowering people with Alzheimer's disease and their caregivers--there is still
      much work to be done.

PMID- 24336765
TI  - Principles of nucleation of H3K27 methylation during embryonic development.
AB  - During embryonic development, maintenance of cell identity and lineage commitment
      requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27
      trimethylation (H3K27me3). However, the developmental origins of this regulation
      are unknown. Here we show that H3K27me3 enrichment increases from blastula stages
      onward in embryos of the Western clawed frog (Xenopus tropicalis) within
      constrained domains strictly defined by sequence. Strikingly, although PRC2 also
      binds widely to active enhancers, H3K27me3 is only deposited at a small subset of
      these sites. Using a Support Vector Machine algorithm, these sequences can be
      predicted accurately on the basis of DNA sequence alone, with a sequence
      signature conserved between humans, frogs, and fish. These regions correspond to
      the subset of blastula-stage DNA methylation-free domains that are depleted for
      activating promoter motifs, and enriched for motifs of developmental factors.
      These results imply a genetic-default model in which a preexisting absence of DNA
      methylation is the major determinant of H3K27 methylation when not opposed by
      transcriptional activation. The sequence and motif signatures reveal the
      hierarchical and genetically inheritable features of epigenetic cross-talk that
      impose constraints on Polycomb regulation and guide H3K27 methylation during the
      exit of pluripotency. 

PMID- 24336767
TI  - Does a 'Singing Together Group' improve the quality of life of people with a
      dementia and their carers? A pilot evaluation study.
AB  - Ten people with dementia (PWD) and their family carers participated in a Singing
      Together Group for 10 weeks and measures of mood, quality of life, PWD's
      behavioural and psychological problems, activities of daily living and cognitive
      status were measured at pre, post and 10-week follow-up. Engagement levels were
      monitored during the sessions and care partners asked to rate each session.
      Additional qualitative information was obtained through interview pre-post and at
      follow-up and subjected to thematic analysis. The results showed that PWD were
      deteriorating slowly over the course of the study on all measures but that they
      and their carers' quality of life remained relatively stable. Engagement levels
      during the group were very high and attendance excellent. Qualitative data gave
      strong support to the group having promoted wellbeing of all participants and
      Nolan's 'Senses Framework' was used to explore this further. Future research
      directions are suggested.

PMID- 24336768
TI  - Experiences of spouses of people with dementia in long-term care.
AB  - The experiences of 10 spouses of people with dementia in long-term care were
      explored using semi-structured interviews. The data were analysed using
      interpretative phenomenological analysis (IPA) which resulted in four themes:
      'Identity: till death us do part'; 'Making sense of change'; 'Relationship with
      care provided: visiting as surveillance'; and 'Relationship with the future: hope
      versus despair'. The findings highlighted the presence of conflicting feelings
      for the spouses, with positive feelings being voiced against a context of
      despair. Their perceptions of the care provided and the spousal relationship also
      highlighted the value of their views in supporting this group of people,
      improving dementia care and, hence, the importance of their involvement in
      implementing a 'relationship-centred' care approach.

PMID- 24336769
TI  - Studying the self in people with dementia: how might we proceed?
AB  - The impact of dementia on the self has become the subject of much research over
      the last few years, mainly due to the implications for support and care for
      people with dementia. However, there are a number of limitations of this research
      that make it difficult to integrate the existing evidence and to draw any firm
      conclusions regarding the persistence of self. This highlights the need for a
      different approach to studying the self in people with dementia in order to
      obtain more robust evidence from future studies. This paper attempts to integrate
      current research using an existing systematic and comprehensive framework of the
      self, and outlines the advantages and limitations of using such a framework as
      the basis for future studies.

PMID- 24336770
TI  - A critique of the evidence base for non-pharmacological sleep interventions for
      persons with dementia.
AB  - Disordered sleep in persons with dementia is a contributing factor for a range of
      health problems. The evidence base for non-pharmacological interventions has not
      been evaluated and clearly presented in the literature. This paper provides a
      structured Critical Literature Review of the evidence for non-pharmacological
      interventions to reduce disordered sleep in persons with dementia. The systematic
      search retrieved 29 studies that were evaluated for methodological quality. The
      quality of evidence ranged from conclusive for light therapy and activity to
      inconclusive for most other interventions. There is a paucity of conclusive
      research for non-pharmacological sleep interventions for persons with dementia.
      Most of the evidence about effective interventions is anecdotal and untested.
      There is a need for rigorous scientific inquiry, coupled with tacit knowledge to
      build a strong evidence base on non-pharmacological interventions for disordered
      sleep for persons with dementia.

PMID- 24336771
TI  - Male caregiving in dementia: a review and commentary.
AB  - In this paper we present a review of the literature on men caring for a relative
      with dementia. While there is an abundance of literature on caregiving in
      general, there is a dearth of information on male caregiving and in particular on
      the role of sons as carers. Keywords used were dementia, Alzheimer's disease,
      caregiver, caregiver burden, caregiver support, sons, spouses, husbands, men,
      fathers, male, widowers, help seeking behaviour, parent child relations, gender
      identity and combinations of these. The inclusion criteria stipulated that papers
      had to be research based, written in English, published between the years 1999
      and 2010 and related to men caring for a person with dementia. The categories
      that emerged from the literature included men in a caregiving role, gender
      differences in caregiver burden, support services and sons as carers. Further
      research is needed to highlight the needs and experiences of men in a caregiving
      role.

PMID- 24336772
TI  - Exploring the gap between rhetoric and reality in dementia care in Australia:
      could practice documents help bridge the great divide?
AB  - Quality of care, and indeed, quality of life, for people living with dementia in
      long-term care is often underpinned by philosophies of care, such as person
      centred care and relationship-centred care. The translation of these philosophies
      into practice is influenced by a range of individual and organizational features,
      including the context in which such care occurs. Within modern care
      organizations, the context of care is evidenced through organizational documents.
      This study sought to identify the key documents guiding dementia care within one
      large Australian long-term care organization and to explore points of consistency
      and tension within the documented system of care. Results highlight a lack of
      consistency and clarity in the philosophy of dementia care and a disconnection
      between the key documents guiding practice. This disconnection creates tension
      for clinicians and carers, and may contribute to the gap between rhetoric and
      reality in dementia care. This study suggests that a congruent documented
      dementia system can help bridge the gap between espoused philosophies of care and
      everyday care practices.

PMID- 24336773
TI  - The management of behavioural and psychological symptoms of dementia in
      residential homes: does Tai Chi have any role for people with dementia?
AB  - Dementia is a common illness that is increasing in frequency and set to challenge
      the resources and expertise of health and social care services over the coming
      years. Increasingly, there has been interest in the management of behavioural and
      psychological symptoms of dementia (BPSD), as they are both common and associated
      with a range of negative outcomes. BPSD are associated with the admission of
      people with dementia to care homes. Limited resources and lack of knowledge in
      permanent care settings often lead to BPSD being managed with antipsychotic
      medications, which are associated with significant morbidity and mortality. There
      is evidence for the benefits of exercise within care home settings, although only
      a few studies include those with cognitive impairment. Tai Chi is a mind-body
      exercise combining relaxed physical movement and meditation, and has been
      suggested to have many health benefits. This article discusses the rationale and
      available options for treating BPSD and the current practice and reviews the
      literature regarding the benefits of exercise and, in particular, Tai Chi in the
      management of BPSD.

PMID- 24336774
TI  - Giant saphenous vein graft aneurysm presenting as stridor.

PMID- 24336775
TI  - The functional evaluation of waste yuzu (Citrus junos) seeds.
AB  - We have succeeded in extracting a large amount of expensive limonoids and the
      high total antioxidant capability yuzu seed oil from waste yuzu seed by simple
      methods. Yuzu seeds contain higher amounts of fat-soluble limonoid aglycone
      (330.6 mg g(-1) of dry seed), water-soluble limonoid glycoside (452.0 mg g(-1) of
      dry seed), and oil (40 mg g(-1) of green seed) than other citrus fruits. The
      antioxidant activities of yuzu seed aglycone, glycoside, and seed oil were
      evaluated in vitro. The potential antioxidant activity in oil solution,
      diphenylpicrylhydrazyl radical-scavenging activity, and hydrogen peroxide
      scavenging activity effects of the seed extracts were also investigated. The
      antioxidant activity of yuzu seed oil was two times that of grapefruit seed oil,
      which has high activity. Yuzu glycoside produced the same high antioxidant
      activity as Luo Han Guo glycoside. 

PMID- 24336777
TI  - Durable spatiotemporal surveillance of Caenorhabditis elegans response to
      environmental cues.
AB  - Animal response to changes in environmental cues is a complex dynamical process
      that occurs at diverse molecular and cellular levels. To gain a quantitative
      understanding of such processes, it is desirable to observe many individuals,
      subjected to repeatable and well defined environmental cues over long time
      periods. Here we present WormSpa, a microfluidic system where worms are
      individually confined in optimized chambers. We show that worms in WormSpa are
      neither stressed nor starved, and in particular exhibit pumping and egg-laying
      behaviors equivalent to those of freely behaving worms. We demonstrate the
      applicability of WormSpa for studying stress response and physiological
      processes. WormSpa is simple to make and easy to operate, and its design is
      modular, making it straightforward to incorporate available microfluidic
      technologies. We expect that WormSpa would open novel avenues of research,
      hitherto impossible or impractical. 

PMID- 24336778
TI  - Thermodynamic stability of La2Mo2-yWyO9, La2Mo2-yWyO8.96+0.02y and La7Mo7(2
      y)/2W7y/2O30 (y = 0, 0.5 and 1.0).
AB  - The role of W content on the limit oxygen partial pressure (pO2) for stability of
      fast oxygen-ion conductors La2Mo2-yWyO9 with y = 0, 0.5 and 1.0 has been studied
      by means of thermogravimetric analysis (TGA) under controlled atmospheres. At 718
      degrees C, below the pO2 stability limit of La2Mo2-yWyO9, the perovskite related
      compounds La7Mo7(2-y)/2W7y/2O30 were stabilized even for y = 1.0. At 608  degrees
      C, the first stage of reduction of beta-La2Mo2-yWyO9 leads to the formation of
      the crystallized oxygen deficient La2Mo2-yWyO8.6+0.02y phase. X-ray powder
      diffraction shows that the stabilization of the high temperature beta-form
      through tungsten substitution observed in fully oxidized La2Mo2-yWyO9 samples is
      preserved upon slight reduction. The n-type conductivity arising from the mixed
      valence state of molybdenum becomes less and less predominant as the W content
      increases. Further reduction causes amorphization. At both temperatures, W
      substitution does not enhance the thermodynamic stability of the La2Mo2-yWyO9 ion
      conductor under a reducing atmosphere but only slows down the kinetics of
      reduction. 

PMID- 24336779
TI  - The anti-inflammatory effect of a pomegranate husk extract on inflamed adipocytes
      and macrophages cultivated independently, but not on the inflammatory vicious
      cycle between adipocytes and macrophages.
AB  - Obese adipose tissues contain a higher proportion of inflamed macrophages than
      the normal adipose tissue. Adipocytes and macrophages are known to secrete pro
      inflammatory markers that establish the systemic inflammation leading to
      metabolic complications. CCL-2 secreted by hypertrophied adipocytes attracts and
      activates macrophages in the adipose tissue. These cells, in turn, secrete
      TNFalpha and other pro-inflammatory molecules. The pomegranate husk extract and
      its phenolic constituents, punicalagin and ellagic acid, have exhibited an anti
      inflammatory effect. In this study, we used an in vitro coculture system of 3T3
      L1 murine adipocytes and RAW 264.7 macrophages to investigate the potential anti
      inflammatory effects of these compounds on the vicious cycle between both cell
      types. The pomegranate husk extract presented an anti-inflammatory effect on the
      inflamed cells cultivated independently, as suggested by a decrease of (i) CCL-2
      secretion by both cell types, (ii) adipocyte IL-6 expression and secretion, and
      (iii) macrophage TNFalpha secretion. Nevertheless and surprisingly, no anti
      inflammatory effect was observed in coculture. Punicalagin, at the same
      concentration as that found in the pomegranate extract, had a more potent effect
      than the extract and in coculture; it reduced significantly the IL-6 secretion.
      Ellagic acid decreased TNFalpha and CCL-2 macrophage secretion, CCL-2 adipocyte
      secretion and, in coculture, it reduced IL-6 secretion and expression by
      adipocytes. These results indicate that the pomegranate husk extract has an anti
      inflammatory action on adipocytes and macrophages but seems to be not able to
      reduce the inflammatory vicious cycle between both cells. Ellagitannin and
      punicalagin showed a better effect on inflammation suggesting that PHE will be a
      good candidate for more investigations. 

PMID- 24336780
TI  - Amorphous alumina nanowire array efficiently delivers Ac-DEVD-CHO to inhibit
      apoptosis of dendritic cells.
AB  - To create an effective well-ordered delivery platform still remains a challenge.
      Herein we fabricate vertically aligned alumina nanowire arrays via atomic layer
      deposition templated by carbon nanotubes. Using these arrays, a caspase-3/7
      inhibitor was delivered into DC 2.4 cells and blocked apoptosis, as confirmed by
      fluorescence microscopy. 

PMID- 24336781
TI  - Fly model causes neurological rethink.
AB  - A Drosophila model for a neurological disorder called type 2B Charcot-Marie-Tooth
      disease reveals that it has its origins in a partial loss of function, rather
      than a gain of function, which points to the need for a new therapeutic approach.

PMID- 24336782
TI  - Is sternotomy superior to thoracotomy for modified Blalock-Taussig shunt?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: is sternotomy approach superior to a
      thoracotomy approach for a modified Blalock-Taussig shunt procedure? More than 58
      papers were found using the search as described below, of which 11 papers
      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. Three of seven
      papers compared the sternotomy and thoracotomy approaches. The operative approach
      was a significant predictor of shunt failure. The criterion used to define early
      shunt failure was either the complete occlusion during hospitalization or the
      need to return to the operating room for a second shunt. The studies that
      compared the thoracotomy and sternotomy approaches observed increased shunt
      failure rates in the thoracotomy group. The sternotomy approach was associated
      with advantages like less pulmonary artery distortion, ease of technical
      performance, cosmetic advantage of a single sternotomy incision, ease of ligation
      of patent ductus, less phrenic nerve injury, less collateral formation in chest
      wall adhesions and less thoracotomy induced scoliosis. However, other papers
      studied either the sternotomy approach only or the thoracotomy approach and drew
      conclusions regarding risk factors for operative morbidity and mortality. We
      conclude that the sternotomy approach is beneficial to neonates and infants
      undergoing modified Blalock-Taussig shunt when compared with the conventional
      thoracotomy approach. 

PMID- 24336783
TI  - Guideline adherence in antithrombotic treatment after concomitant ablation
      surgery in atrial fibrillation patients.
AB  - OBJECTIVES: We investigated real-life oral anticoagulation (OAC) treatment after
      surgical ablation and examined its adherence to current recommendations. We also
      explored factors related to OAC use preoperatively and at follow-up. METHODS: One
      hundred and fifteen patients with atrial fibrillation (AF) were evaluated during
      12-month follow-up after surgery. Patients were divided into two categories
      according to the congestive heart failure, hypertension, age >=75 years, diabetes
      and prior stroke [or transient ischaemic attack or thromboembolism] (CHADS2)
      score: 60 patients were assigned to the high-risk group (CHADS2 score >=2) and 55
      to the low-risk group (CHADS2 score <=1). OAC use was defined as guideline
      adherent, undertreatment or overtreatment. RESULTS: Baseline overall guideline
      adherence was 62%. OAC was underprescribed in high-risk patients and
      overprescribed in low-risk patients (both, P < 0.001). The only factor associated
      with OAC use after logistic regression analysis were age >75 years (P = 0.01) and
      preoperative AF > paroxysmal (P = 0.013). Overall guideline adherence at 12-month
      follow-up showed a trend towards a better adherence in the sinus rhythm (SR)
      subgroup (74% vs 55%, P = 0.02). OAC was underprescribed in high-risk patients
      and overprescribed in low-risk patients (both P < 0.001). After logistic
      regression analysis, preoperative OAC use (P = 0.007) and other indications for
      OAC (P = 0.01) were predictors of anticoagulation treatment. CONCLUSIONS: Real
      life OAC prescription in AF patients showed a moderate guideline adherence, with
      high-risk patients being undertreated and low-risk patients being overtreated.
      These findings stress the importance that antithrombotic treatment in patients
      undergoing AF surgery needs to be critically re-evaluated.

PMID- 24336784
TI  - Percutaneous extracorporeal life support for patients in therapy refractory
      cardiogenic shock: initial results of an interdisciplinary team.
AB  - OBJECTIVES: Therapy refractory cardiogenic shock is associated with dismal
      outcome. Percutaneous implantation of an extracorporeal life support (ECLS)
      system achieves immediate cardiopulmonary stabilization, sufficient end-organ
      perfusion and reduction of subsequent multiorgan failure (MOF). METHODS: Forty
      one patients undergoing percutaneous ECLS implantation for cardiogenic shock from
      February 2012 until August 2013 were retrospectively analysed. Mean age was 52 +/
      13 years, 6 (15%) were female. Mean pH values obtained before ECLS implantation
      were 7.15 +/- 0.24, mean lactate concentration was 11.7 +/- 6.4 mmol/l. Levels
      obtained 6 h after ECLS implantation were 7.30 +/- 0.14 and 8.7 +/- 5.0 mmol/l,
      respectively. In 23 patients (56%) cardiogenic shock resulted from an acute
      coronary syndrome in 13 (32%) from cardiomyopathy, in 5 (12%) from other causes.
      Twenty-seven (66%) had been resuscitated, in 14 (34%) implantation was performed
      under ongoing cardiopulmonary resuscitation (CPR). Of note, 97% of the acute
      coronary syndrome patients underwent percutaneous coronary intervention (PCI)
      either before ECLS implantation or under ECLS support. Extracorporeal life
      support implantation was performed on scene (Emergency Department, Cath Lab,
      Intensive Care Unit) by a senior cardiac surgeon and a trained perfusionist, in 8
      cases (20%) in the referring hospital. RESULTS: Thirty-day mortality was 51% [21
      patients, due to MOF (n = 14), cerebral complications (n = 6) and heart failure
      (n = 1)]. Logistic regression analysis identified 6-h pH values as an independent
      risk factor of 30-day mortality (P < 0.001, OR = 0.000, 95% CI 0.000-0.042).
      Neither CPR nor implantation under ongoing CPR resulted in significant
      differences. In 26 cases (63%), the ECLS system could be explanted, after mean
      support of 169 +/- 67 h. Seven of these patients received cardiac surgery
      [ventricular assist device implantation (n = 4), heart transplantation (n = 1),
      other procedures (n = 2)]. CONCLUSIONS: Due to the evolution of transportable
      ECLS systems and percutaneous techniques implantation on scene is feasible.
      Extracorporeal life support may serve as a bridge-to-decision and bridge-to
      treatment device. Neurological evaluation before ventricular assist device
      implantation and PCI under stable conditions are possible. Despite substantial
      mortality, ECLS implantation in selected patients by an experienced team offers
      additional support to conventional therapy as well as CPR and allows survival in
      patients that otherwise most likely would have died. This concept has to be
      implemented in cardiac survival networks in the future.

PMID- 24336785
TI  - The effect of butorphanol postconditioning on myocardial ischaemia reperfusion
      injury in rats.
AB  - OBJECTIVES: Butorphanol tartrate is a synthetic opioid partial agonist analgesic.
      Butorphanol targets the heart, mainly via kappa-opioid receptor (kappa-OR)
      activation. The purpose of this study was to determine the effect and mechanism
      underlying butorphanol postconditioning (B-Post) on myocardial ischaemia
      reperfusion injury in rats. METHODS: Seventy-five male Sprague-Dawley rats were
      randomly divided into five groups of 15 each: Group sham; Group I/R
      (ischaemia/reperfusion); Group B (butorphanol postconditioning); Group B/N
      (butorphanol postconditioning + antagonist of kappa-OR nor-binaltorphimine [Nor
      BNI]); Group B/G (butorphanol postconditioning + nonselective ATP-sensitive
      potassium (KATP) channel blocker glibenclamide [GLI]). The left coronary anterior
      descending artery (LAD) was occluded for 30 min, followed by a 120-min
      reperfusion. Blood samples were obtained at the end of reperfusion for
      determination of serum tumour necrosis factor (TNF)-alpha and interleukin (IL)-6
      concentrations. The hearts were then excised for determination of myocardial
      infarct size by triphenyltetrazolium chloride staining. The myocardial tissues
      were used for determination of the expression of myocardial superoxide dismutase
      (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO). RESULTS: Myocardial
      infarct size was significantly reduced in B (26.4 +/- 1.83%), B/N (34.5 +/-
      1.56%) and B/G (31.5 +/- 1.27%) Groups compared with Group I/R (46.8 +/- 1.41%)
      (all P < 0. 001). The serum TNF-alpha and IL-6 concentrations and the MDA and MPO
      activities in the ischaemic area in B, B/N and B/G Groups were significantly
      lower than those in the I/R Group (all P < 0.001). In addition, myocardial
      infarct size, TNF-alpha and IL-6 concentrations and the MDA and MPO activities in
      B/N and B/G Groups were higher than those in the B Group (all P < 0.001). In
      contrast, SOD activity was significantly increased in B, B/N and B/G Groups, and
      SOD activity in B/N and B/G Groups was less than in the B Group (all P < 0.001).
      CONCLUSIONS: These results suggest that postconditioning of butorphanol tartrate
      can provide a potent cardioprotective effect against myocardial ischaemic and
      reperfusion injury. Both the kappa-OR and the KATP channels were involved in this
      effect.

PMID- 24336787
TI  - Effects of eugenol-reduced clove extract on glycogen phosphorylase b and the
      development of diabetes in db/db mice.
AB  - We found that the 50% aqueous EtOH extract of clove (Syzygium aromaticum) had
      potent dose-dependent inhibitory activity toward glycogen phosphorylase b and
      glucagon-stimulated glucose production in primary rat hepatocytes. Among the
      components, eugeniin inhibited glycogen phosphorylase b and glucagon-stimulated
      glucose production in primary rat hepatocytes, with IC50 values of 0.14 and 4.7
      MUM, respectively. In sharp contrast, eugenol showed no significant inhibition
      toward glycogen phosphorylase b, even at a concentration of 400 MUM. Eugenol
      reduced clove extracts (erCE) were prepared and when fed to a db/db mouse they
      clearly suppressed the blood glucose and HbA1c levels. Furthermore, plasma
      triglyceride and non-esterified fatty acid levels in 5% and 10% erCE-fed db/db
      mice were significantly lowered, compared with control db/db mice without erCE
      supplementation. These results suggested that dietary supplementation with the
      erCE could beneficially modify glucose and lipid metabolism and contribute to the
      prevention of the progress of hyperglycemia and metabolic syndrome. 

PMID- 24336789
TI  - Treatment dependence in chronic inflammatory demyelinating
      polyradiculoneuropathy: is it related to disease phenotype or to the therapy
      used?

PMID- 24336790
TI  - Dominant spinal muscular atrophy due to BICD2: a novel mutation refines the
      phenotype.

PMID- 24336791
TI  - Pharmacokinetics of intravenous immunoglobulin in multifocal motor neuropathy.
AB  - BACKGROUND: Multifocal motor neuropathy (MMN) is often responsive to treatment
      with intravenous immunoglobulin (IVIg), but the optimal dose and intervals of
      IVIg maintenance treatment have not been established. Increase in IgG
      concentration (DeltaIgG) after IVIg infusion has recently been identified as
      determinant of outcome in Guillain-Barre syndrome. DeltaIgG may therefore
      represent a potentially useful biomarker to optimise IVIg dosing in patients with
      MMN. OBJECTIVE: The aims of this study were to determine variability of IVIg
      pharmacokinetics in patients with MMN in relation to treatment response, and to
      establish whether interindividual differences in IVIg pharmacokinetics were
      associated with genetic polymorphisms of the endothelial IgG receptor (FcRn)
      which determines IgG half-life. METHODS: Twenty-three patients with MMN receiving
      their first IVIg treatment at a cumulative dose of 2.0 g/kg in 5 days were
      included. A good treatment response was defined as an increase in muscle strength
      of at least one Medical Research Council point in minimally two muscle groups.
      IgG concentrations in serum were determined at baseline, at day 1 and day 5 of
      the IVIg course, and 3 weeks after treatment. FcRn copy number variation and
      differences in repeat length of the variable number of tandem repeats in the FcRn
      gene were determined by quantitative PCR and Sanger sequencing. RESULTS:
      Seventeen patients (74%) had a good response to treatment. Total IgG and DeltaIgG
      levels showed large variation between patients. Mean DeltaIgG was higher in IVIg
      responders than in non-responders, with the largest difference on day 1 (11.1 g/L
      vs 4.5 g/L, p=0.06), but our study lacked power to show statistically significant
      differences. Genetic variation in the FcRn gene was not associated with DeltaIgG
      levels or response to treatment. CONCLUSIONS: IVIg pharmacokinetics varies in
      patients with MMN and may be associated with clinical response.

PMID- 24336792
TI  - Postoperative Clostridium difficile infection with PCR ribotype 078 strain
      identified at necropsy in five Thoroughbred racehorses.
AB  - Clostridium difficile is an important cause of acute enterocolitis in horses. We
      describe five cases of C difficile infection occurring postoperatively in
      Thoroughbred racehorses. Following diarrhoea or colic accompanied by a marked
      increase in packed cell volume (to >=60 per cent) and leucopenia (<=4000
      cells/MUl) within two to four days after surgery in all five horses, four of them
      died or were euthanased because of colitis or severe diarrhoea. In these four
      horses, necrotising entero-typhlo-colitis was revealed by postmortem examination,
      and C difficile was recovered from the contents of the small and/or large
      intestine. The remaining horse was euthanased because of marked decline in
      general condition and the presence of a lung abscess, from which C difficile was
      isolated. The horse had had severe postoperative diarrhoea before the onset of
      respiratory disorder; laboratory tests for C difficile were not performed on the
      faeces. All C difficile isolates were toxin-A-positive, toxin-B-positive and
      actin-specific ADP-ribosyltransferase (CDT)-positive. The isolates were
      indistinguishable by pulsed field gel electrophoresis analysis, PCR ribotyping,
      and slpA sequence typing, and the slpA sequences and PCR ribotype patterns were
      identical to those of known PCR type 078. This case sequence might have been
      healthcare-associated infection, although there was about a four-month interval
      between each disease onset.

PMID- 24336793
TI  - Effect of period, water temperature and agitation on loss of water-soluble
      carbohydrates and protein from grass hay: implications for equine feeding
      management.
AB  - The effects of different water-soaking treatments on removal of water-soluble
      carbohydrates (WSC), WSC constituents and protein from four UK hays were
      determined. Hays were soaked in water for up to 16 hours at mean temperatures of
      8 degrees C, 16 degrees C, in hot tap water (initially 49 degrees C) or agitated
      and rinsed in clean water at 16 degrees C. Initial hay WSC contents ranged from
      154 to 216 g/kg dry matter. Losses of WSC from hays after 16 hours soaking at 8
      degrees C, 16 degrees C, 16 degrees C plus agitation and 49 degrees C averaged
      28, 46, 49 and 44 per cent, respectively. Corresponding percentage losses of
      fructan were 16, 37, 39 and 33. Percentage losses of sucrose averaged 55 (8
      degrees C), 86 (16 degrees C), 91 (16 degrees C+agitation) and 82 (initial
      temperature 49 degrees C), those of glucose were 60, 85, 75 and 75, and of
      fructose were 41, 52, 54 and 46. Hay crude protein contents were not
      significantly changed by any of the soaking treatments. Soaking at 8 degrees C
      generally resulted in reduced losses of WSC compared to when soaked at the higher
      temperatures. Thus, in cold weather using warmer water to soak hays may effect
      greater WSC loss, although very prolonged soaking at warm temperatures might
      encourage the proliferation of unwanted micro-organisms in the soak liquor. 

PMID- 24336794
TI  - Mycobacteriosis outbreak caused by Mycobacterium avium subsp. avium detected
      through meat inspection in five porcine fattening farms.

PMID- 24336795
TI  - Mini-Konno procedure using a 10 mm handmade valve for pulmonary atresia with
      intact ventricular septum and severe aortic stenosis.
AB  - We herein report the case of a neonate with pulmonary atresia with intact
      ventricular septum, right ventricular hypoplasia and severe aortic stenosis.
      Repetitive aortic valve surgeries in early infancy resulted in early relapse of
      the aortic stenosis due to the small aortic annulus, bicuspid configuration and
      duct-dependent pulmonary circulation. The infant underwent a successful mini
      Konno procedure using a 10 mm handmade valve and bidirectional Glenn shunt at 6
      months of age. 

PMID- 24336797
TI  - Efficient scavenging of beta-carotene radical cations by antiinflammatory
      salicylates.
AB  - The radical cation generated during photobleaching of beta-carotene is scavenged
      efficiently by the anion of methyl salicylate from wintergreen oil in a second
      order reaction approaching the diffusion limit with k2 = 3.2 * 10(9) L mol(-1) s(
      1) in 9 : 1 v/v chloroform-methanol at 23  degrees C, less efficiently by the
      anion of salicylic acid with 2.2 * 10(8) L mol(-1) s(-1), but still of possible
      importance for light-exposed tissue. Surprisingly, acetylsalicylate, the aspirin
      anion, reacts with an intermediate rate in a reaction assigned to the anion of
      the mixed acetic-salicylic acid anhydride formed through base induced
      rearrangements. The relative scavenging rate of the beta-carotene radical cation
      by the three salicylates is supported by DFT-calculations. 

PMID- 24336798
TI  - Complexation of Cm(III) and Eu(III) with CyMe4-BTPhen and CyMe4-BTBP studied by
      time resolved laser fluorescence spectroscopy.
AB  - The complexation of Cm(III) and Eu(III) with 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8
      tetrahydro-1,2,4-benzotriazin-3-yl)-1,10-phenanthroline (CyMe4-BTPhen) and 6,6'
      bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2'
      bipyridine (CyMe4-BTBP) in methanolic solution was investigated by TRLFS. For
      both ligands, the 1:2 complex with the particular metal ion is the only species
      observed in equilibrated samples. The species distribution for various ligand
      concentrations was determined and stability constants of the 1:2 complexes were
      derived (log beta2 = 13.8 +/- 0.2 (Cm(III)-CyMe4-BTPhen), log beta2 = 11.6 +/-
      0.4 (Eu(III)-CyMe4-BTPhen), log beta2 = 12.4 +/- 0.3 (Cm(III)-CyMe4-BTBP) and log
      beta2 = 11.3 +/- 0.3 (Eu(III)-CyMe4-BTBP)). Biphasic experiments in combination
      with TRLFS studies on the organic phase revealed the formation of ternary
      complexes with two CyMe4-BTPhen or -BTBP molecules and additional coordination of
      a nitrate anion as species formed during the extraction process.

PMID- 24336796
TI  - Rasgrp1 mutation increases naive T-cell CD44 expression and drives mTOR-dependent
      accumulation of Helios+ T cells and autoantibodies.
AB  - Missense variants are a major source of human genetic variation. Here we analyze
      a new mouse missense variant, Rasgrp1(Anaef), with an ENU-mutated EF hand in the
      Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1(Anaef) mice exhibit anti
      nuclear autoantibodies and gradually accumulate a CD44(hi) Helios(+) PD-1(+)
      CD4(+) T cell population that is dependent on B cells. Despite reduced Rasgrp1
      Ras-ERK activation in vitro, thymocyte selection in Rasgrp1(Anaef) is mostly
      normal in vivo, although CD44 is overexpressed on naive thymocytes and T cells in
      a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter
      of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a
      reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs
      in Rasgrp1(Anaef) naive CD4(+) T cells. CD44 expression, CD4(+) T cell subset
      ratios and serum autoantibodies all returned to normal in
      Rasgrp1(Anaef)Mtor(chino) double-mutant mice, demonstrating that increased mTOR
      activity is essential for the Rasgrp1(Anaef) T cell dysregulation. DOI:
      http://dx.doi.org/10.7554/eLife.01020.001. 

PMID- 24336799
TI  - Clinically relevant frailty index for mice.
AB  - Frailty is a clinical syndrome associated with the aging process and adverse
      outcomes. The purpose of this short report was to initiate the development of a
      Frailty Index in 27- to 28-month-old C57BL/6 mice that matched the clinical
      criteria used in humans (weakness, slow walking speed, low activity level, poor
      endurance). The selected criteria included grip strength, walking speed, physical
      activity, and endurance. The criteria in mice were evaluated by the inverted
      cling grip test, rotarod test, voluntary wheel running, and derived endurance
      scores. Each criterion had a designated cutoff point (1.5 SD below the cohort
      mean) to identify the mice with the lowest performance. If a mouse presented with
      three of the criteria scores below the cutoff points, it was identified as frail.
      Mild frailty was designated if two criteria were below the cutoff points. In this
      mouse cohort, one mouse was identified as frail and one was mildly frail. This
      prevalence of 9% frailty is consistent with the prevalence of frailty in humans
      at the same survival age. Collectively, our selected criterion, cutoff point, and
      Frailty Index provide a potential standardized definition for frailty in mice
      that is consistent with the operational definition of frailty in humans.

PMID- 24336801
TI  - Curved polymer nanodiscs by wetting nanopores of anodic aluminum oxide templates
      with polymer nanospheres.
AB  - Although nanostructures with diverse morphologies have been fabricated, it is
      still a great challenge to prepare anisotropic two-dimensional (2-D)
      nanostructures, especially non-planar disc-like nanostructures. In this work, we
      develop a simple method to prepare curved polymer nanodiscs with regular sizes by
      wetting polymer nanospheres in the nanopores of anodic aluminum oxide (AAO)
      templates. Polystyrene (PS) nanospheres are first fabricated by using a non
      solvent-assisted template wetting method. By annealing the PS nanospheres in the
      nanopores of AAO templates, curved PS nanodiscs can be produced. The length and
      morphology of the curved PS nanodiscs can be controlled by the wetting conditions
      such as the annealing temperatures and times. For some stacked nanospheres, the
      annealing process can result in the formation of helix-like nanostructures. To
      demonstrate the universality of this work, this approach is also applied to
      poly(methyl methacrylate) (PMMA), another common polymer, and similar results are
      obtained. 

PMID- 24336800
TI  - Lower extremity function trajectories in the African American Health Cohort.
AB  - BACKGROUND: We addressed two understudied issues in estimating lower extremity
      functional trajectories in older adults-incorporating the effect of mortality and
      evaluating heterogeneity among African Americans. METHODS: Data were taken from
      the 998 participants in the African American Health cohort. A highly reliable and
      valid 8-item lower extremity function scale was used at baseline and at the 1-, 2
      , 3-, 4-, 7-, and 9-year follow-up interviews. Semiparametric (ie, discrete)
      group-based mixture modeling identified the trajectories, and multinomial
      logistic regression identified risk factors for differential trajectory groups.
      RESULTS: When treating mortality as informative censoring, six discrete
      trajectories were observed with 45% of the participants belonging to three stable
      trajectories (good, fair, or poor function), and the remainder belonging to three
      declining trajectories (very high function with minimal improvement then minimal
      decline, very good function with a slow and modest decline, and very good
      function with a large and quick decline). CONCLUSION: Substantial heterogeneity
      in lower extremity function trajectories exists in the African American Health
      cohort, after appropriately treating mortality as informative censoring.

PMID- 24336802
TI  - Ion effects at electrode/solid polymer electrolyte membrane interfaces.
AB  - The differential capacity and the potential distribution at electrode/solid
      polymer electrolyte membrane/solution interfaces are calculated through an
      analytical approach. The model considers coions' and counterions' permeation
      through the membrane from the solvent phase and the ions' partitioning
      equilibrium at the SPEM/solution interface. The latter effects are included by
      incorporating the Donnan equilibrium, the steric hindrance, the solvation energy
      change when ions move from water to membrane pores and ion electrostatic
      interactions. It is shown that capacitance maxima in capacitance-potential curves
      may appear because of the acid-base dissociation process inside the membrane and
      the change in the ions' total interaction energy with the applied potential. For
      low dielectric constants inside membrane pores, epsilonp, sharp peaks can be
      obtained. These peaks broaden, decrease in magnitude and shift to positive
      potentials once epsilonp is increased. Finally, model predictions are discussed
      in light of recent experimental data obtained on Nafion(r) covered Pt(111)
      electrodes, providing a theoretical framework for the qualitative electroanalysis
      of these systems. 

PMID- 24336803
TI  - Li(0.8)Mg(2.1)B2O5F: the first borate fluoride with magnesium-oxygen-fluorine
      octahedral chains.
AB  - The first alkali metal and magnesium mixed borate fluoride, Li(0.8)Mg(2.1)B2O5F,
      was prepared by the high-temperature solution method. It crystallizes in the
      monoclinic space group P2(1)/n (no. 14) with lattice constants a = 3.0881(4) A, b
      = 13.6020(2) A, c = 9.6563(1) A, beta = 91.744(9) degrees , Z = 4. In the
      structure, a special magnesium-oxygen-fluorine octahedral chain is found in
      borates for the first time. The octahedral chains are linked into a three
      dimensional framework containing tunnels with (1)(infinity)[LiO4](7-) chains and
      isolated B2O5 groups filling in. The differences of octahedral chains in
      Li(0.8)Mg(2.1)B2O5F and magnesium inosilicate minerals are discussed. The TG-DSC
      curves, IR spectrum and UV-Vis-NIR diffuse reflectance spectrum were measured.

PMID- 24336804
TI  - DIVE: a data intensive visualization engine.
AB  - SUMMARY: Modern scientific investigation is generating increasingly larger
      datasets, yet analyzing these data with current tools is challenging. DIVE is a
      software framework intended to facilitate big data analysis and reduce the time
      to scientific insight. Here, we present features of the framework and demonstrate
      DIVE's application to the Dynameomics project, looking specifically at two
      proteins. AVAILABILITY AND IMPLEMENTATION: Binaries and documentation are
      available at http://www.dynameomics.org/DIVE/DIVESetup.exe.

PMID- 24336805
TI  - Causal analysis approaches in Ingenuity Pathway Analysis.
AB  - MOTIVATION: Prior biological knowledge greatly facilitates the meaningful
      interpretation of gene-expression data. Causal networks constructed from
      individual relationships curated from the literature are particularly suited for
      this task, since they create mechanistic hypotheses that explain the expression
      changes observed in datasets. RESULTS: We present and discuss a suite of
      algorithms and tools for inferring and scoring regulator networks upstream of
      gene-expression data based on a large-scale causal network derived from the
      Ingenuity Knowledge Base. We extend the method to predict downstream effects on
      biological functions and diseases and demonstrate the validity of our approach by
      applying it to example datasets. AVAILABILITY: The causal analytics tools
      'Upstream Regulator Analysis', 'Mechanistic Networks', 'Causal Network Analysis'
      and 'Downstream Effects Analysis' are implemented and available within Ingenuity
      Pathway Analysis (IPA, http://www.ingenuity.com). SUPPLEMENTARY INFORMATION:
      Supplementary material is available at Bioinformatics online.

PMID- 24336806
TI  - NetCoffee: a fast and accurate global alignment approach to identify functionally
      conserved proteins in multiple networks.
AB  - MOTIVATION: Owing to recent advancements in high-throughput technologies, protein
      protein interaction networks of more and more species become available in public
      databases. The question of how to identify functionally conserved proteins across
      species attracts a lot of attention in computational biology. Network alignments
      provide a systematic way to solve this problem. However, most existing alignment
      tools encounter limitations in tackling this problem. Therefore, the demand for
      faster and more efficient alignment tools is growing. RESULTS: We present a fast
      and accurate algorithm, NetCoffee, which allows to find a global alignment of
      multiple protein-protein interaction networks. NetCoffee searches for a global
      alignment by maximizing a target function using simulated annealing on a set of
      weighted bipartite graphs that are constructed using a triplet approach similar
      to T-Coffee. To assess its performance, NetCoffee was applied to four real
      datasets. Our results suggest that NetCoffee remedies several limitations of
      previous algorithms, outperforms all existing alignment tools in terms of speed
      and nevertheless identifies biologically meaningful alignments. AVAILABILITY: The
      source code and data are freely available for download under the GNU GPL v3
      license at https://code.google.com/p/netcoffee/.

PMID- 24336807
TI  - ORCA: a COBRA toolbox extension for model-driven discovery and analysis.
AB  - SUMMARY: Over past decades, constraint-based modelling has emerged as an
      important approach to obtain referential information about mechanisms behind
      biological phenotypes and identify physiological and perturbed metabolic states
      at genome-scale. However, application of this novel approach to systems biology
      in biotechnology is still hindered by the functionalities of the existing
      modelling software. To augment the usability of the constraint-based approach for
      various use scenarios, we present ORCA, a Matlab package, which extends the scope
      of established Constraint-Based Reconstruction and Analysis metabolic modelling
      and includes three unique functionalities: (i) a framework method integrating
      three analyses of multi-objective optimization, robustness analysis and
      fractional benefit analysis, (ii) metabolic pathways identification with futile
      loop elimination and (iii) a dynamic flux balance analysis framework
      incorporating kinetic constraints. AVAILABILITY AND IMPLEMENTATION: ORCA is
      freely available to academic users and is downloadable from
      https://sourceforge.net/projects/exorca/; a mini-tutorial is supplied in the
      package for training purposes as well as a software manual.

PMID- 24336808
TI  - ProbeSelect: selecting differentially expressed probes in transcriptional profile
      data.
AB  - SUMMARY: Transcriptional profiling still remains one of the most popular
      techniques for identifying relevant biomarkers in patient samples. However,
      heterogeneity in the population leads to poor statistical evidence for selection
      of most relevant biomarkers to pursue. In particular, human transcriptional
      differences can be subtle, making it difficult to tease out real differentially
      expressed biomarkers from the variability inherent in the population. To address
      this issue, we propose a simple statistical technique that identifies
      differentially expressed probes in heterogeneous populations as compared with
      controls. AVAILABILITY AND IMPLEMENTATION: The algorithm has been implemented in
      Java and available at www.sourceforge.net/projects/probeselect.

PMID- 24336809
TI  - NeuroPID: a predictor for identifying neuropeptide precursors from metazoan
      proteomes.
AB  - MOTIVATION: The evolution of multicellular organisms is associated with
      increasing variability of molecules governing behavioral and physiological
      states. This is often achieved by neuropeptides (NPs) that are produced in
      neurons from a longer protein, named neuropeptide precursor (NPP). The maturation
      of NPs occurs through a sequence of proteolytic cleavages. The difficulty in
      identifying NPPs is a consequence of their diversity and the lack of applicable
      sequence similarity among the short functionally related NPs. RESULTS: Herein, we
      describe Neuropeptide Precursor Identifier (NeuroPID), a machine learning scheme
      that predicts metazoan NPPs. NeuroPID was trained on hundreds of identified NPPs
      from the UniProtKB database. Some 600 features were extracted from the primary
      sequences and processed using support vector machines (SVM) and ensemble decision
      tree classifiers. These features combined biophysical, chemical and informational
      statistical properties of NPs and NPPs. Other features were guided by the
      defining characteristics of the dibasic cleavage sites motif. NeuroPID reached 89
      94% accuracy and 90-93% precision in cross-validation blind tests against known
      NPPs (with an emphasis on Chordata and Arthropoda). NeuroPID also identified NPP
      like proteins from extensively studied model organisms as well as from poorly
      annotated proteomes. We then focused on the most significant sets of features
      that contribute to the success of the classifiers. We propose that NPPs are
      attractive targets for investigating and modulating behavior, metabolism and
      homeostasis and that a rich repertoire of NPs remains to be identified.
      AVAILABILITY: NeuroPID source code is freely available at
      http://www.protonet.cs.huji.ac.il/neuropid

PMID- 24336810
TI  - Development and evaluation of a clinical staging system for amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Staging of disease severity is useful for prognosis, decision-making
      and resource planning. However, no commonly used, validated staging system exists
      for amyotrophic lateral sclerosis (ALS). Our purpose was to develop an ALS
      staging system (ALS Milano-Torino Staging) that captures the observed progressive
      loss of independence and function. METHODS: Clinical milestones in ALS
      progression were defined by loss of independence in four key domains on the ALS
      Functional Rating Scale (ALSFRS): swallowing, walking/self-care, communicating
      and breathing. Stages were defined as follows: stage 0, functional involvement
      but no loss of independence on any domain; stages 1-4, number of domains in which
      independence was lost; and stage 5, death. Staging criteria were applied to
      patients enrolled in a Quality of Care in ALS (QOC) study; endpoints included
      function (ALSFRS), quality of life (QOL; Short Form-36) and health service costs.
      Between-stage transition probabilities were assessed in the QOC study and in a
      second clinical study of lithium carbonate in ALS. RESULTS: 70/118 (59.3%)
      participants in the QOC study progressed to higher stages of disease at 12 months
      compared with their baseline stage. Functional (ALSFRS) and QOL measures were
      inversely related to disease stage. Health service costs were directly related to
      increasing disease stages from 0 to 4 (p<0.001). Probabilities for transitioning
      from a given stage at baseline in both studies were usually greatest for the next
      highest stage. CONCLUSIONS: The proposed ALS Milano-Torino Staging system
      correlates well with assessments of function, QOL and health service costs.
      Further studies are warranted to validate this system.

PMID- 24336812
TI  - Bandgap engineering of colloidal zinc oxysulfide via lattice substitution with
      sulfur.
AB  - Zinc oxysulfide nanocrystals with zinc blende phase are synthesized through a wet
      chemical method. An affirmation of the crystal structure, elemental homogeneity
      and phase transformation is obtained by X-ray diffraction and authenticated by
      electron micrographic studies. Theoretical observations have strongly supported
      the thermodynamic solubility limit for its (30%) formation. An anomalous bandgap
      bowing with modulation in bandgap from 3.74 eV (ZnO) to 3.93 eV (ZnS) was
      observed with a minimum bandgap of 2.7 eV. Tunable bandgap and a wide range of
      visible emission ascertain it as a potential material for optoelectronic and
      solar cell applications due to its large bandgap offsets. 

PMID- 24336811
TI  - Single cell gene expression analysis in injury-induced collective cell migration.
AB  - Collective cell behavior in response to mechanical injury is central to various
      regenerative and pathological processes. Using a double-stranded locked nucleic
      acid probe for monitoring real-time intracellular gene expression, we examined
      the spatiotemporal response of epithelial cells during injury-induced collective
      migration and compared to the blocker assay with minimal injury as control. We
      showed that cells ~150 MUm from the wound edge exhibit a gradient in response to
      mechanical injury, expressing different genes depending on the wounding process.
      While release of contact inhibition is sufficient to trigger the migratory
      behavior, cell injury additionally induces reactive oxygen species, Nrf2 protein,
      and stress response genes, including heat shock protein 70 and heme oxygenase-1,
      in a spatiotemporal manner. Furthermore, we show that Nrf2 has an inhibitory role
      in injury-induced epithelial-mesenchymal transition, suggesting a potential
      autoregulatory mechanism in injury-induced response. Taken together, our single
      cell gene expression analyses reveal modular cell responses to mechanical injury,
      manipulation of which may afford novel strategies for tissue repair and
      prevention of tumor invasion in the future. 

PMID- 24336813
TI  - Fe3O4@MOF core-shell magnetic microspheres as excellent catalysts for the Claisen
      Schmidt condensation reaction.
AB  - Separation and recycling of catalysts after catalytic reactions are critically
      required to reduce the cost of catalysts as well as to avoid the generation of
      waste in industrial applications. In this work, we present a facile fabrication
      and characterization of a novel type of MOF-based porous catalyst, namely,
      Fe3O4@MIL-100(Fe) core-shell magnetic microspheres. It has been shown that these
      catalysts not only exhibit high catalytic activities for the Claisen-Schmidt
      condensation reactions under environmentally friendly conditions, but remarkably,
      they can be easily separated and recycled without significant loss of catalytic
      efficiency after being used for many times. Therefore, compared to other reported
      catalysts used in the Claisen-Schmidt condensation reactions, these catalysts are
      green, cheap and more suitable for large scale industrial applications.

PMID- 24336817
TI  - Halogen bond-assisted electron transfer reactions of aliphatic bromosubstituted
      electrophiles.
AB  - Isolation of pre-reactive complexes and analysis of kinetics of redox reactions
      of tetrabromomethane and tribromonitromethane demonstrated that halogen bonding
      results in significant lowering of the activation barriers for electron transfer,
      and that the rate constants of such (inner-sphere) processes can be evaluated
      from spectral, structural, and thermodynamic characteristics of the halogen
      bonded associates. 

PMID- 24336816
TI  - Estimating bias from loss to follow-up in a prospective cohort study of bicycle
      crash injuries.
AB  - BACKGROUND: Loss to follow-up, if related to exposures, confounders and outcomes
      of interest, may bias association estimates. We estimated the magnitude and
      direction of such bias in a prospective cohort study of crash injury among
      cyclists. METHODS: The Taupo Bicycle Study involved 2590 adult cyclists recruited
      from New Zealand's largest cycling event in 2006 and followed over a median
      period of 4.6 years through linkage to four administrative databases. We
      resurveyed the participants in 2009 and excluded three participants who died
      prior to the resurvey. We compared baseline characteristics and crash outcomes of
      the baseline (2006) and follow-up (those who responded in 2009) cohorts by ratios
      of relative frequencies and estimated potential bias from loss to follow-up on
      seven exposure-outcome associations of interest by ratios of HRs. RESULTS: Of the
      2587 cyclists in the baseline cohort, 1526 (60%) responded to the follow-up
      survey. The responders were older, more educated and more socioeconomically
      advantaged. They were more experienced cyclists who often rode in a bunch, off
      road or in the dark, but were less likely to engage in other risky cycling
      behaviours. Additionally, they experienced bicycle crashes more frequently during
      follow-up. The selection bias ranged between -10% and +9% for selected
      associations. CONCLUSIONS: Loss to follow-up was differential by demographic,
      cycling and behavioural risk characteristics as well as crash outcomes, but did
      not substantially bias association estimates of primary research interest.

PMID- 24336818
TI  - The influence of Shc proteins on life span in mice.
AB  - The signaling molecule p66Shc is often described as a longevity protein. This
      conclusion is based on a single life span study that used a small number of mice.
      The purpose of the present studies was to measure life span in a sufficient
      number of mice to determine if longevity is altered in mice with decreased Shc
      levels (ShcKO). Studies were completed at UC Davis and the European Institute of
      Oncology (EIO). At UC Davis, male C57BL/6J WT and ShcKO mice were fed 5% or 40%
      calorie-restricted (CR) diets. In the 5% CR group, there was no difference in
      survival curves between genotypes. There was also no difference between genotypes
      in prevalence of neoplasms or other measures of end-of-life pathology. At 40%
      calorie restriction group, 70th percentile survival was increased in ShcKO, while
      there were no differences between genotypes in median or subsequent life span
      measures. At EIO, there was no increase in life span in ShcKO male or female mice
      on C57BL/6J, 129Sv, or hybrid C57BL/6J-129Sv backgrounds. These studies indicate
      that p66Shc is not a longevity protein. However, additional studies are needed to
      determine the extent to which Shc proteins may influence the onset and severity
      of specific age-related diseases.

PMID- 24336819
TI  - Assessing the "physical cliff": detailed quantification of age-related
      differences in daily patterns of physical activity.
AB  - BACKGROUND: In spite of evidence that physical activity has beneficial effects on
      health and age-related functional decline, there is a scarcity of detailed and
      accurate information on objectively measured daily activity and patterns of such
      activity in older adults. METHODS: Participants in the Baltimore Longitudinal
      Study of Aging (n = 611, 50% male, mean age 67, range 32-93) wore the Actiheart
      portable activity monitor for 7 days in the free-living environment. The
      association between activity and age was modeled using a continuous log-linear
      regression of activity counts on age with sex, body mass index, employment
      status, functional performance, and comorbid conditions as covariates. RESULTS:
      In the fully adjusted model, continuous analyses demonstrated that overall
      physical activity counts were 1.3% lower for each year increase in age. Although
      there were no differences among morning levels of activity, there was
      significantly lower afternoon and evening activity in older individuals (p <
      .01). After adjusting for age, poor functional performance, nonworking status,
      and higher body mass index were independently associated with less physical
      activity (p < .001). CONCLUSIONS: The use of accelerometers to characterize
      minute-by-minute intensity, cumulative physical activity counts, and daily
      activity patterns provides detailed data not gathered by traditional subjective
      methods, particularly at low levels of activity. The findings of a 1.3% decrease
      per year in activity from mid-to-late life, and the corresponding drop in
      afternoon and evening activity, provide new information that may be useful when
      targeting future interventions. Further, this methodology addresses essential
      gaps in understanding activity patterns and trends in more sedentary sectors of
      the population.

PMID- 24336820
TI  - Effectiveness of co-trimoxazole to prevent Plasmodium falciparum malaria in HIV
      positive pregnant women in sub-Saharan Africa: an open-label, randomized
      controlled trial.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) and malaria during pregnancy cause
      substantial perinatal mortality. As co-trimoxazole (CMX) protects children and
      HIV-positive adults against malaria, we compared the effectiveness of daily CMX
      with sulfadoxine-pyrimethamine intermittent preventive treatment (IPT-SP) on
      malaria risk in HIV-positive pregnant women in a Plasmodium falciparum-endemic
      African area. METHODS:  From January 2009 to April 2011, we included in a
      randomized noninferiority trial all HIV type 1-infected pregnant women (<=28
      weeks' gestation, CD4 count >=200 cells/uL, hemoglobin level >=7 g/L) in 19
      health centers in Togo. Women were randomly assigned to daily 800 mg/160 mg CMX,
      or IPT-SP. The primary outcome was the proportion of malaria-free pregnancies.
      Other outcomes included malaria incidence, parasitemia, placental malaria,
      anemia, and infants' birth weight. RESULTS: Of 264 women randomly assigned to the
      CMX or IPT-SP group, 126 of 132 and 124 of 132, respectively, were included in
      the analysis. There were 33 confirmed cases of clinical malaria among 31 women in
      the CMX group, and 19 among 19 women in the IPT-SP group. Ninety-five of 126
      (75.4%) women in the CMX group and 105 of 124 (84.7%) in the IPT-SP group
      remained malaria-free during their pregnancy (difference, 9.3%; 95% confidence
      interval [CI], -.53 to 19.1, not meeting the predefined noninferiority
      criterion). The incidence rate in intention-to-treat analysis was 108.8 malaria
      episodes per 100 person-years in CMX (95% CI, 105.4-112.2) and 90.1 in IPT-SP
      (95% CI, 86.8-93.4) (not significant). Prevalence of parasitemia was 16.7% in the
      CMX group vs 28% in the IPT-SP group (P = .02). Histology revealed 20.3%
      placental malaria in the CMX group vs. 24.6% in the IPT-SP group (not
      significant). Grade 3-4 anemia was more frequent in the CMX group (10% vs 4%; P =
      .008). No pregnant women died. Median birth weight was similar. CONCLUSIONS: 
      Daily CMX was not noninferior to IPT-SP for preventing maternal malaria but safe
      and at least similar regarding parasitemia or placental malaria and birth
      outcomes. Clinical Trials Registration  ISRCTN98835811.

PMID- 24336821
TI  - Next-generation sequencing for identifying pyrazinamide resistance in
      Mycobacterium tuberculosis.

PMID- 24336822
TI  - Preventing malaria in HIV-infected pregnant women.

PMID- 24336824
TI  - Editorial commentary: Reversing latency in HIV-infected patients.

PMID- 24336825
TI  - Why do some human viruses remain recalcitrant to cultivation?

PMID- 24336823
TI  - A systematic review of Borrelia burgdorferi morphologic variants does not support
      a role in chronic Lyme disease.
AB  - BACKGROUND:  Much of the controversy that surrounds Lyme disease pertains to
      whether it produces prolonged, treatment-refractory infection, usually referred
      to as chronic Lyme disease. Some have proposed that round morphologic variants of
      Borrelia burgdorferi, known variably as "cyst forms" and "L-forms," are
      responsible for the pathogenesis of chronic Lyme disease. We have undertaken a
      systematic review of the literature to determine if there is a documented role of
      these variants in Lyme disease pathogenesis or in syndromes compatible with
      chronic Lyme disease. METHODS:  Two systematic literature searches were performed
      to identify studies in which round morphologic variants of B. burgdorferi have
      been described in situ in human specimens. RESULTS:  Our primary literature
      search identified 6 studies that reported round morphologic variants of B.
      burgdorferi in specimens obtained from 32 total patients. No study described
      these forms in patients who had purely subjective symptom complexes (eg, fatigue
      or pain). No study investigated a causal relationship between morphologic
      variants and clinical disease or evaluated treatment of morphologic variants in
      vivo. Of 29 additional studies that described the morphology of B. burgdorferi
      from patients with Lyme disease, the organism was invariably described as having
      spirochetal morphology. CONCLUSIONS:  In the context of the broader medical
      literature, it is not currently possible to ascribe a pathogenic role to
      morphologic variants of B. burgdorferi in either typical manifestations of Lyme
      disease or in other chronic disease states that are often labeled chronic Lyme
      disease. There is no clinical literature to justify specific treatment of B.
      burgdorferi morphologic variants.

PMID- 24336826
TI  - In memoriam: John P. Quinn, MD.

PMID- 24336827
TI  - Utility of (1-3)-beta-D-glucan testing for diagnostics and monitoring response to
      treatment during the multistate outbreak of fungal meningitis and other
      infections.
AB  - BACKGROUND:  The 2012 outbreak of fungal meningitis associated with contaminated
      methylprednisolone produced by a compounding pharmacy has resulted in >750
      infections. An important question facing patients and clinicians is the duration
      of antifungal therapy. We evaluated (1-3)-beta-d-glucan (BDG) as a marker for
      monitoring response to treatment. METHODS:  We determined sensitivity and
      specificity of BDG testing using the Fungitell assay, by testing 41 cerebrospinal
      fluid (CSF) specimens from confirmed cases of fungal meningitis and 66 negative
      control CSF specimens. We also assessed whether BDG levels correlate with
      clinical status by using incident samples from 108 case patients with meningitis
      and 20 patients with serially collected CSF. RESULTS:  A cutoff value of 138
      pg/mL provided 100% sensitivity and 98% specificity for diagnosis of fungal
      meningitis in this outbreak. Patients with serially collected CSF were divided
      into 2 groups: those in whom BDG levels declined with treatment and those in whom
      BDG remained elevated. Whereas most patients with a decline in CSF BDG had
      clinical improvement, all 3 patients with continually elevated BDG had poor
      clinical outcomes (stroke, meningitis relapse, or development of new disease).
      CONCLUSIONS:  Our data suggest that measuring BDG in CSF is a highly sensitive
      test for diagnosis of fungal meningitis in this outbreak. Analysis of BDG levels
      in serially collected CSF demonstrated that BDG may correlate with clinical
      response. Routine measurement of BDG in CSF may provide useful adjunctive data
      for the clinical management of patients with outbreak-associated meningitis.

PMID- 24336828
TI  - A pilot study assessing the safety and latency-reversing activity of disulfiram
      in HIV-1-infected adults on antiretroviral therapy.
AB  - BACKGROUND: Transcriptionally silent human immunodeficiency virus type 1 (HIV-1)
      DNA persists in resting memory CD4(+) T cells despite antiretroviral therapy. In
      a primary cell model, the antialcoholism drug disulfiram has been shown to induce
      HIV-1 transcription in latently infected resting memory CD4(+) T cells at
      concentrations achieved in vivo. METHODS: We conducted a single-arm pilot study
      to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1
      infected individuals on stable suppressive antiretroviral therapy would result in
      reversal of HIV-1 latency with a concomitant transient increase in residual
      viremia or depletion of the latent reservoir in resting memory CD4(+) T cells.
      RESULTS: Disulfiram was safe and well tolerated. There was a high level of
      subject-to-subject variability in plasma disulfiram levels. The latent reservoir
      did not change significantly (1.16-fold change; 95% confidence interval [CI], .70
      to 1.92-fold; P = .56). During disulfiram administration, residual viremia did
      not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69
      fold; P = .13), although residual viremia was estimated to increase by 1.88-fold
      compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P
      = .04). In a post hoc analysis, a rapid and transient increase in viremia was
      noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1
      RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). CONCLUSIONS:
      Administration of disulfiram to patients on antiretroviral therapy does not
      reduce the size of the latent reservoir. A possible dose-related effect on
      residual viremia supports future studies assessing the impact of higher doses on
      HIV-1 production. Disulfiram affects relevant signaling pathways and can be
      safely administered, supporting future studies of this drug.

PMID- 24336830
TI  - Applying a new technology to an old question: whole-genome sequencing and
      Staphylococcus aureus acquisition in an intensive care unit.

PMID- 24336829
TI  - Whole-genome sequencing shows that patient-to-patient transmission rarely
      accounts for acquisition of Staphylococcus aureus in an intensive care unit.
AB  - BACKGROUND:  Strategies to prevent Staphylococcus aureus infection in hospitals
      focus on patient-to-patient transmission. We used whole-genome sequencing to
      investigate the role of colonized patients as the source of new S. aureus
      acquisitions, and the reliability of identifying patient-to-patient transmission
      using the conventional approach of spa typing and overlapping patient stay.
      METHODS: Over 14 months, all unselected patients admitted to an adult intensive
      care unit (ICU) were serially screened for S. aureus. All available isolates (n =
      275) were spa typed and underwent whole-genome sequencing to investigate their
      relatedness at high resolution. RESULTS: Staphylococcus aureus was carried by 185
      of 1109 patients sampled within 24 hours of ICU admission (16.7%); 59 (5.3%)
      patients carried methicillin-resistant S. aureus (MRSA). Forty-four S. aureus (22
      MRSA) acquisitions while on ICU were detected. Isolates were available for
      genetic analysis from 37 acquisitions. Whole-genome sequencing indicated that 7
      of these 37 (18.9%) were transmissions from other colonized patients.
      Conventional methods (spa typing combined with overlapping patient stay) falsely
      identified 3 patient-to-patient transmissions (all MRSA) and failed to detect 2
      acquisitions and 4 transmissions (2 MRSA). CONCLUSIONS: Only a minority of S.
      aureus acquisitions can be explained by patient-to-patient transmission. Whole
      genome sequencing provides the resolution to disprove transmission events
      indicated by conventional methods and also to reveal otherwise unsuspected
      transmission events. Whole-genome sequencing should replace conventional methods
      for detection of nosocomial S. aureus transmission.

PMID- 24336831
TI  - Synthesis and structural characterization of dioxomolybdenum and dioxotungsten
      hydroxamato complexes and their function in the protection of radiation induced
      DNA damage.
AB  - The synthesis and structural characterization of two novel dioxomolybdenum(VI)
      (1) and dioxotungsten(VI) (2) complexes with 2-phenylacetylhydroxamic acid (PAHH)
      [M(O)2(PAH)2] [M = Mo, W] have been accomplished. The dioxomolybdenum(VI) and
      dioxotungsten(VI) moiety is coordinated by the hydroxamate group (-CONHO(-)) of
      the 2-phenylacetylhydroxamate (PAH) ligand in a bi-dentate fashion. In both the
      complexes the PAHH ligand is coordinated through oxygen atoms forming a five
      membered chelate. The hydrogen atom of N-H of the hydroxamate group is engaged in
      intermolecular H-bonding with the carbonyl oxygen of another coordinated
      hydroxamate ligand, thereby forming an extended 1D chain. The ligand as well as
      both the complexes exhibit the ability to protect from radiation induced damage
      both in CTDNA as well as in pUC19 plasmid DNA. As the damage to DNA is caused by
      the radicals generated during radiolysis, its scavenging imparts protection from
      the damage to DNA. To understand the mechanism of protection, binding affinities
      of the ligand and the complex with DNA were determined using absorption and
      emission spectral studies and viscosity measurements, whereby the results
      indicate that both the complexes and the hydroxamate ligand interact with calf
      thymus DNA in the minor groove. The intrinsic binding constants, obtained from UV
      vis studies, are 7.2 * 10(3) M(-1), 5.2 * 10(4) M(-1) and 1.2 * 10(4) M(-1) for
      the ligand and complexes 1 and 2 respectively. The Stern-Volmer quenching
      constants obtained from a luminescence study for both the complexes are 5.6 *
      10(4) M(-1) and 1.6 * 10(4) M(-1) respectively. The dioxomolybdenum(VI) complex
      is found to be a more potent radioprotector compared to the dioxotungsten(VI)
      complex and the ligand. Radical scavenging chemical studies suggest that the
      complexes have a greater ability to scavenge both the hydroxyl as well as the
      superoxide radicals compared to the ligand. The free radical scavenging ability
      of the ligand and the complexes was further established by EPR spectroscopy using
      a stable free radical, the DPPH, as a probe. The experimental results of DNA
      binding are further supported by molecular docking studies.

PMID- 24336832
TI  - Targeting adequate thermal stability and fire safety in selecting ionic liquid
      based electrolytes for energy storage.
AB  - The energy storage market relating to lithium based systems regularly grows in
      size and expands in terms of a portfolio of energy and power demanding
      applications. Thus safety focused research must more than ever accompany related
      technological breakthroughs regarding performance of cells, resulting in
      intensive research on the chemistry and materials science to design more reliable
      batteries. Formulating electrolyte solutions with nonvolatile and hardly
      flammable ionic liquids instead of actual carbonate mixtures could be safer.
      However, few definitions of thermal stability of electrolytes based on ionic
      liquids have been reported in the case of abuse conditions (fire, shortcut,
      overcharge or overdischarge). This work investigates thermal stability up to
      combustion of 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide
      ([C1C4Im][NTf2]) and 1-butyl-1-methylpyrrolidinium
      bis(trifluoromethanesulfonyl)imide ([PYR14][NTf2]) ionic liquids, and their
      corresponding electrolytes containing lithium bis(trifluoromethanesulfonyl)imide
      LiNTf2. Their possible routes of degradation during thermal abuse testings were
      investigated by thermodynamic studies under several experimental conditions.
      Their behaviours under fire were also tested, including the analysis of emitted
      compounds. 

PMID- 24336833
TI  - Defect accommodation in nanostructured soft crystals.
AB  - A detailed analysis of the structure of lyotropic micellar FCC soft crystals was
      performed by scanning small-angle neutron scattering. Soft crystals have a large
      number of structural defects, leading to characteristic features in the
      scattering patterns such as secondary Bragg peaks, diffuse scattering lines, and
      paracrystalline distortions. We find that the presence of a large number of
      defects locally breaks the three-dimensional symmetry of the crystal, leading to
      weakly correlated assemblies of stacked {111} layers. Positional correlations of
      micelles in different layers are very short ranged, with correlation lengths
      corresponding to only a few layers. Within the layers, in-plane positional
      correlations are somewhat longer ranged, but still corresponding to only a few
      unit cells. Depending on the polydispersity, soft crystals accommodate defects to
      form mesocrystals of iso-oriented mosaic domains, or paracrystals. The soft layer
      structures already show characteristic features of two-dimensional systems,
      exhibiting short-range positional order and longer-ranged orientational order,
      with similarities to hexatic and recently observed soft quasicrystalline
      structures. The study shows that defects can be differently accommodated in soft
      crystals, thereby strongly affecting local and macroscopic positional and
      orientational order. 

PMID- 24336834
TI  - Electrical conductivity of insulating polymer nanoscale layers: environmental
      effects.
AB  - As electronic devices are scaled down to submicron sizes, it has become critical
      to obtain uniform and robust insulating nanoscale polymer films. For that reason,
      we address the electrical properties of grafted polymer layers made of
      poly(glycidyl methacrylate), polyacrylic acid, poly(2-vinylpyridine), and
      polystyrene with thicknesses of 10-20 nm. It was found that layers insulating
      under normal ambient conditions can display a significant increase in
      conductivity as the environment changes. Namely, we demonstrated that the in
      plane electrical conductivity of the polymer grafted layers can be changed by at
      least two orders of magnitude upon exposure to water or organic solvent vapors.
      Conductive properties of all polymer grafted films under study could also be
      significantly enhanced with an increase in temperature. The observed phenomenon
      makes possible the chemical design of polymer nanoscale layers with reduced or
      enhanced sensitivity to the anticipated change in environmental conditions.
      Finally, we demonstrated that the observed effects could be used in a micron
      sized conductometric transducing scheme for the detection of volatile organic
      solvents. 

PMID- 24336835
TI  - A biocompatible, highly efficient click reaction and its applications.
AB  - Herein, we review the development, optimization, applications and potential
      prospects of a novel click reaction based on the condensation reaction between 2
      cyanobenzothiazole (CBT) and D-cysteine (D-Cys) in fireflies. This click
      condensation reaction has obvious advantages in biocompatibility, efficiency and
      stability in aqueous environments. Optimization of this click reaction has been
      carried out so that it can be controlled by pH change, reduction, or enzymatic
      cleavage to synthesize large molecules and self-assembled nanostructures, or
      enhance probe signals. Consequently, this CBT-based click reaction has been and
      could be successfully applied to a wide range of biomedical applications such as
      molecular imaging (e.g., optical imaging, nuclear imaging and magnetic resonance
      imaging), biomolecular detection, drug delivery and other potentialities.

PMID- 24336836
TI  - Theoretical investigations toward the tandem reactions of N-aziridinyl imine
      compounds forming triquinanes via trimethylenemethane diyls: mechanisms and
      stereoselectivity.
AB  - In this paper, we have investigated the tandem reaction mechanism for the N
      aziridinyl imine compounds forming triquinanes via trimethylenemethane (TMM)
      diyls in detail. Based on the calculated results, the reaction is initiated by
      the cleavage of the N-aziridinyl in the substrate, followed by an intramolecular
      1,3-dipolar (3 + 2) cycloaddition preferentially leading to a linearly-fused
      tetrahydrocyclopentapyrazole intermediate. Next, the intermediate loses N2 to
      form the singlet TMM diyl M3S, which can then undergo another concerted (3 + 2)
      cycloaddition to generate the linearly-fused cis-trans or cis-syn triquinane
      products. In addition, M3S can also undergo intersystem crossing to the triplet
      TMM diyl M3T, and the six possible reaction pathways associated with M3T have
      also been identified. The calculated results reveal that the cis-trans fused
      pathway associated with M3S is energetically preferred with the highest free
      energy barrier of 25.0 kcal mol(-1). In comparison, the cyclization of M3T
      requires much higher activation free energies (DeltaG(?) = 34.4-57.8 kcal mol(
      1)). At the experimental temperature 110  degrees C, only the linearly-fused cis
      trans and cis-syn pathways associated with M3T (DeltaG(?) = 34.4 and 35.5 kcal
      mol(-1) respectively) are possible. The calculated results also indicate that for
      both M3S and M3T, the linearly-fused cis-trans triquinane should be the main
      product, which is consistent with the experimental observation. At last,
      conformational and NBO analyses on key transition states identified the cis-trans
      stereocontrol factors. Further calculations indicate that the methyl substituent
      on the allene group of the reactant substrate improves the stereoselectivity of
      the reaction but does not affect the rate-determining step.

PMID- 24336838
TI  - Visual detection of telomerase activity with a tunable dynamic range by using a
      gold nanoparticle probe-based hybridization protection strategy.
AB  - We developed a novel telomere complementary (TC) oligonucleotide modified AuNP
      probe (TC-AuNPs) for colorimetric analysis of telomerase activity. The mechanism
      of this method is that the telomerase reaction products (TRP), which can
      hybridize with the TC-AuNPs, are able to protect the AuNPs from the aggregation
      induced by salt. It is demonstrated that the colorimetric method enabled the
      analysis of the telomerase activity in 1000 HeLa cells with the naked eye, and
      down to 100 HeLa cells with the aid of UV-Vis spectroscopy. This strategy is not
      only convenient and sensitive, but also has a tunable dynamic range. The platform
      is also applicable for the initial screening of a telomerase inhibitor to
      discover new anticancer drugs. 

PMID- 24336837
TI  - The preventive effect of the Nordic hamstring exercise on hamstring injuries in
      amateur soccer players: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Hamstring injuries are the most common muscle injury in male amateur
      soccer players and have a high rate of recurrence, often despite extensive
      treatment and long rehabilitation periods. Eccentric strength and flexibility are
      recognised as important modifiable risk factors, which have led to the
      development of eccentric hamstring exercises, such as the Nordic hamstring
      exercise. As the effectiveness of the Nordic hamstring exercise in reducing
      hamstring injuries has never been investigated in amateur soccer players, the aim
      of this study is to investigate the effect of this exercise on the incidence and
      severity of hamstring injuries in male amateur soccer players. An additional aim
      is to determine whether flexibility is associated with hamstring injuries. STUDY
      DESIGN: Cluster-randomised controlled trial with soccer teams as the unit of
      cluster. METHODS: Dutch male amateur soccer players, aged 18-40 years, were
      allocated to an intervention or control group. Both study groups continued
      regular soccer training during 2013, but the intervention group additionally
      performed the Nordic hamstring exercise (25 sessions over 13 weeks). Primary
      outcomes are the incidence of initial and recurrent hamstring injury and injury
      severity. Secondary outcomes are hamstring-and-lower-back flexibility and
      compliance. Compliance to the intervention protocol was also monitored.
      DISCUSSION: Eccentric hamstring strength exercises are hypothesised to reduce the
      incidence of hamstring injury among male amateur soccer players by 70%. The
      prevention of such injuries will be beneficial to soccer players, clubs, football
      associations, health insurance companies and society. TRIAL REGISTRATION:
      NTR3664.

PMID- 24336840
TI  - Hydrothermal synthesis, electronic structure and tunable luminescence of single
      phase Ca5(PO4)3F:Tb3+,Eu3+ microrods.
AB  - Uniform and well-crystallized calcium fluorapatite [Ca5(PO4)3F, FAP] microrods
      have been successfully synthesized by a facile one-step hydrothermal synthesis
      method using sodium citrate as the crystal modifier. X-ray diffraction (XRD),
      field emission-scanning electron microscopy (FE-SEM), transmission electron
      microscopy (TEM), photoluminescence (PL), photoluminescent excitation spectra
      (PLE) and decay studies were employed to characterize the samples. The electronic
      structure and orbital population of FAP were also determined by means of density
      functional theory calculations. Under ultraviolet irradiation, the
      FAP:Tb(3+),Eu(3+) samples exhibit a blue-light emission of the host matrix, as
      well as the typical green emission band of the Tb(3+) ions, and a red-light
      emission of Eu(3+). The highly intense red emission bands of the Eu(3+) ions were
      attributed to the effective energy transfer from the Tb(3+) to Eu(3+) ions, which
      has been justified through the luminescence spectra and the fluorescence decay
      dynamics. The luminescence colors of FAP:Tb(3+),Eu(3+) microrods can be easily
      tuned by changing the concentration of Eu(3+) ions. The results reveal that the
      combination of the self-activated luminescence and rare earth-doping emission in
      FAP:Tb(3+),Eu(3+) microrods could result in tunable emission in a large color
      gamut, which can be used as a potential candidate for white-light-emitting diodes
      and other display devices. 

PMID- 24336841
TI  - Interdroplet bilayer arrays in millifluidic droplet traps from 3D-printed moulds.
AB  - In droplet microfluidics, aqueous droplets are typically separated by an oil
      phase to ensure containment of molecules in individual droplets of nano-to
      picoliter volume. An interesting variation of this method involves bringing two
      phospholipid-coated droplets into contact to form a lipid bilayer in-between the
      droplets. These interdroplet bilayers, created by manual pipetting of microliter
      droplets, have proved advantageous for the study of membrane transport phenomena,
      including ion channel electrophysiology. In this study, we adapted the droplet
      microfluidics methodology to achieve automated formation of interdroplet lipid
      bilayer arrays. We developed a 'millifluidic' chip for microliter droplet
      generation and droplet packing, which is cast from a 3D-printed mould. Droplets
      of 0.7-6.0 MUL volume were packed as homogeneous or heterogeneous linear arrays
      of 2-9 droplets that were stable for at least six hours. The interdroplet
      bilayers had an area of up to 0.56 mm(2), or an equivalent diameter of up to 850
      MUm, as determined from capacitance measurements. We observed osmotic water
      transfer over the bilayers as well as sequential bilayer lysis by the pore
      forming toxin melittin. These millifluidic interdroplet bilayer arrays combine
      the ease of electrical and optical access of manually pipetted microdroplets with
      the automation and reproducibility of microfluidic technologies. Moreover, the 3D
      printing based fabrication strategy enables the rapid implementation of
      alternative channel geometries, e.g. branched arrays, with a design-to-device
      time of just 24-48 hours. 

PMID- 24336839
TI  - Shedding light on protein folding landscapes by single-molecule fluorescence.
AB  - Single-molecule (SM) fluorescence methods have been increasingly instrumental in
      our current understanding of a number of key aspects of protein folding and
      aggregation landscapes over the past decade. With the advantage of a model free
      approach and the power of probing multiple subpopulations and stochastic dynamics
      directly in a heterogeneous structural ensemble, SM methods have emerged as a
      principle technique for studying complex systems such as intrinsically disordered
      proteins (IDPs), globular proteins in the unfolded basin and during folding, and
      early steps of protein aggregation in amyloidogenesis. This review highlights the
      application of these methods in investigating the free energy landscapes, folding
      properties and dynamics of individual protein molecules and their complexes, with
      an emphasis on inherently flexible systems such as IDPs. 

PMID- 24336842
TI  - Synthesis, characterization, DNA binding, cleavage activity and cytotoxicity of
      copper(II) complexes.
AB  - Three new mononuclear copper(II) complexes, [Cu(L2)](2+) (1), [Cu(acac)(L)](+)
      (2), and [Cu(acac-Cl)(L)](+) (3) (L = 2-(4-pyridine)oxazo[4,5-f]1,10
      phenanthroline (4-PDOP); acac = acetylacetone; acac-Cl = 3-chloroacetylacetone),
      have been synthesized and characterized by elemental analysis, high resolution
      mass spectrometry (Q-TOF), and IR spectroscopy. Two of the complexes were
      structurally characterized by single-crystal X-ray diffraction techniques. Their
      interactions with DNA were studied by UV-vis absorption and emission spectra,
      viscosity, thermal melting, DNA unwinding assay and CD spectroscopy. The
      nucleolytic cleavage activity of the compounds was carried out on double stranded
      pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the
      presence and absence of an oxidant (H2O2). Active oxygen intermediates such as
      hydroxyl radicals and hydrogen peroxide generated in the presence of L and
      complexes 1-3 may act as active species for the DNA scission. The cytotoxicity of
      the complexes against HepG2 cancer cells was also studied.

PMID- 24336843
TI  - Synthesis, characterization and reactivity of an imidazolin-2-iminato aluminium
      dihydride.
AB  - The reaction of bis(2,6-diisopropylphenyl)imidazolin-2-imine (LH, 1) with
      Me3N.AlH3 furnishes {MU-LAlH2}2 (2). The marked tendency of 2 to release its
      hydride substituents is ascribed to the strong electron-donor character of the
      imidazolin-2-iminato ligand. This is supported by its reactivity study and DFT
      calculations. In fact, compound 2 was further converted with Me3SiOTf, Me2S.BH3,
      Me2S.BBr3, and BX3 (with X = Cl, Br, and I) into {MU-LAl(H)OTf}2 (3), {MU
      LAl(BH4)2}2 (4), and {MU-LAlX2}2 (5, X = Br; 6, X = Cl; 7, X = I), respectively.
      For all new aluminium complexes the formulation as dimers was evidenced by high
      resolution mass spectrometry, as well as single-crystal X-ray diffraction
      analysis. A prominent structural motif of these compounds is the square-planar
      four-membered Al2N2 ring with two bridging bulky imidazolin-2-imino moieties.

PMID- 24336844
TI  - Housing wealth, psychological well-being, and cognitive functioning of older
      Americans.
AB  - OBJECTIVES: Economic security around retirement age may be an important
      determinant of psychological and cognitive well-being of older adults. This study
      examines the impact of the dramatic increase in housing prices from the mid-1990s
      to the mid-2000s on psychological and cognitive outcomes among Americans born
      between 1924 and 1960. METHOD: Our quasi-experimental empirical strategy exploits
      geographic differences in housing market price trends during the housing boom
      (from the mid-1990s until 2006). We use individual-level data from the Health and
      Retirement Study (HRS) and estimates of housing values from DataQuick, a
      California-based real estate consultancy firm, to estimate the association of
      housing price increases with psychological and cognitive outcomes at follow-up.
      RESULTS: Greater housing appreciation over the follow-up period was associated
      with a significantly lower risk of anxiety (for women) and an improved
      performance on some but not all cognitive tasks. Effects for depressive symptoms,
      positive and negative affect, and life satisfaction were all in the beneficial
      direction but not statistically significant. The effects of price run-ups were
      concentrated on homeowners, as opposed to renters, suggestive of wealth-driven
      effects. DISCUSSION: Housing market volatility may influence the psychological
      and cognitive health of older adults, highlighting potential health consequences
      of pro-home ownership policies, which may be especially important in light of
      recent dramatic housing price declines.

PMID- 24336845
TI  - Coexistence of minicircular and a highly rearranged mtDNA molecule suggests that
      recombination shapes mitochondrial genome organization.
AB  - Recombination has been proposed as a possible mechanism to explain mitochondrial
      (mt) gene rearrangements, although the issue of whether mtDNA recombination
      occurs in animals has been controversial. In this study, we sequenced the entire
      mt genome of the megaspilid wasp Conostigmus sp., which possessed a highly
      rearranged mt genome. The sequence of the A+T-rich region contained a number of
      different types of repeats, similar to those reported previously in the nematode
      Meloidogyne javanica, in which recombination was discovered. In Conostigmus, we
      detected the end products of recombination: a range of minicircles. However,
      using isolated (cloned) fragments of the A+T-rich region, we established that
      some of these minicircles were found to be polymerase chain reaction (PCR)
      artifacts. It appears that regions with repeats are prone to PCR template
      switching or PCR jumping. Nevertheless, there is strong evidence that one
      minicircle is real, as amplification primers that straddle the putative
      breakpoint junction produce a single strong amplicon from genomic DNA but not
      from the cloned A+T-rich region. The results provide support for the direct link
      between recombination and mt gene rearrangement. Furthermore, we developed a
      model of recombination which is important for our understanding of mtDNA
      evolution. 

PMID- 24336846
TI  - Sphenoid mucocele: a rare cause of ocular dysfunction.

PMID- 24336847
TI  - Quantity or quality? Implications for postgraduate medical training system in
      China.

PMID- 24336848
TI  - Anti-Ro 52 positive dermatomyositis presenting as rapidly progressive
      interstitial lung disease.

PMID- 24336849
TI  - Malignant spinal cord compression: NICE guidance, improvements and challenges.
AB  - BACKGROUND AND AIM: Malignant spinal cord compression (mSCC) is one of the most
      serious complications of cancer. Recent NICE guidance has aimed to improve
      patient pathways and outcomes for patients with mSCC. We have examined the
      current presentations, management and outcomes for patients with mSCC in West
      London following the implementation of the NICE guidance. MATERIALS AND METHODS:
      The electronic records and clinical notes were reviewed for all patients assessed
      for confirmed or potential mSCC at Charing Cross Hospital in 2012. Details on the
      number of referrals, the proportion with confirmed mSCC, the cancer diagnosis,
      treatment and outcome were analysed. RESULTS: 191 patients were reviewed with 127
      (66%) cases of confirmed mSCC. The commonest tumour types were prostate cancer
      (26 cases), lung cancer (26), breast cancer (21) and kidney cancer (15). 21% of
      the patients had no previous cancer diagnosis; mSCC was their presenting
      diagnostic event. Radiotherapy was the predominant management, 24% of the
      patients had first line surgical treatment. At presentation 62% of patients were
      either chair or bed bound. Treatment brought important mobility benefits to all
      patients groups with 20% of the initially chair or bed bound patients leaving the
      hospital with independent mobility. CONCLUSION: Enhanced patients pathways with
      ease of access, rapid assessment and prompt treatment can improve outcomes.
      Despite these pathways many patients still present with gross motor impairment
      and over 20% have no previous diagnosis of cancer. Ongoing work to maintain
      awareness for patients and primary care of the diagnosis and emergency pathways
      is essential to optimize outcomes.

PMID- 24336851
TI  - Embodiment and dementia.

PMID- 24336850
TI  - Cancer risk among gingivitis and periodontitis patients: a nationwide cohort
      study.
AB  - AIM: Periodontal disease encompasses gingivitis and periodontitis, which exerts
      systemic effects. We conducted a population-based study to evaluate the
      association between periodontal disease and the risk of cancer. METHODS: We used
      insurance claims data from 1997 to 2010, accessing a database of 1 million
      randomly selected insurants in Taiwan. All patients were older than 20 and newly
      diagnosed with periodontitis between 1 January 1997 and 31 December 2010. The
      comparison cohort comprised patients older than 20, who were newly diagnosed with
      gingivitis in the same period. Both cohorts were followed until a cancer
      diagnosis, lost to follow-up, death, termination of insurance, or the end of
      2010. RESULTS: The incidence rate of cancer was 1.14 times higher in the study
      cohort than in the comparison cohort [confidence interval (CI) = 1.11-1.17]. The
      adjusted hazard ratio (HR) was 1.05 (95% CI = 1.00-1.11). A multivariable
      analysis showed that the periodontitis patients exhibited an elevated risk of
      developing oral cancer (adjusted HR = 1.79, 95% CI = 1.42-2.25). CONCLUSION: The
      findings indicated that patients in the periodontitis cohort exhibited a higher
      risk of developing oral cancer than those in the gingivitis cohort.

PMID- 24336852
TI  - Embodiment and dementia: exploring critical narratives of selfhood, surveillance,
      and dementia care.
AB  - In the last decade there has been a notable increase in efforts to expand
      understandings of dementia by incorporating the body and theorizing its
      interrelationship with the larger social order. This emerging subfield of
      dementia studies puts the body and embodied practices at the center of
      explorations of how dementia is represented and/or experienced. This shift
      towards a greater recognition of the way that humans are embodied has expanded
      the horizon of dementia studies, providing the intellectual and narrative
      resources to examine experiences of dementia, and their interconnections with
      history, culture, power, and discourse. Our aim in this paper is to critically
      explore and review dimensions of this expanding research and literature,
      specifically in relation to three key narratives: (1) rethinking selfhood:
      exploring embodied dimensions; (2) surveillance, discipline, and the body in
      dementia and dementia care; and (3) embodied innovations in dementia care
      practice. We argue that this literature collectively destabilizes dementia as a
      taken-for-granted category and has generated critical texts on the
      interrelationship between the body and social and political processes in the
      production and expression of dementia. 

PMID- 24336853
TI  - Dementia, personhood and embodiment: what can we learn from the medieval history
      of memory?
AB  - Memory and dementia are historical ideas that preceded the development of modern
      neuroscientific, psychogeriatric and medical approaches to aging and cognitive
      impairment. This article explores the value of such historical ideas in order to
      understand the discourses and metaphors by which Western thought has
      individualized memory as the guarantor of rational personhood, while at the same,
      treating memory decline as a threat to healthy and successful aging. Discussion
      focuses on the relationship between memory and the body in the classical and
      medieval ars memoria (the art of memory) and in the early modern philosophies of
      personhood, particularly the work of John Locke. Conclusions consider the
      significance of Western culture's history of embodied memory as it moved from
      cosmic to individual to neurocognitive sites for our wider views about the
      treatment of dementia. 

PMID- 24336854
TI  - Dementia and the biopolitics of the biopic: from Iris to The iron lady.
AB  - This article considers the question of embodiment through a comparative analysis
      of two 'biopics', Iris (2001) and The Iron Lady (2011), which both feature
      eponymous characters that have, or had, dementia. Embodiment draws our attention
      to the representation of the body in the films themselves, and to the socially
      significant 'feelings' or affects that circulate within and are reproduced around
      them. Shame, disgust and aversion are socially devastating affects conventionally
      associated with stigmatised bodies including those of the cognitively impaired
      but attention to the 'feeling tone' (Ngai, 2005) in these films demonstrates that
      a more varied range of affects and embodied social knowledge is produced.
      Embodiment is thus a starting point to explore what is at stake in these films
      both in their authorisation of particular versions of public lives and for their
      significance for the cultural politics of representation in the context of
      explorations of personhood and dementia. 

PMID- 24336855
TI  - Dress, dementia and the embodiment of identity.
AB  - The article explores the significance of dress in the embodied experience of
      dementia, exploring questions of identity, memory and relationship. It suggests
      that clothing and dress are important in the analysis of the day-to-day
      experiences of people with dementia, giving access to dimensions of selfhood
      often ignored in over-cognitive accounts of being. As a result clothing and dress
      can be significant to the provision of person-centred dementia care. These
      arguments are explored through ideas of embodied identity, the materialisation of
      memories, and the maintenance, or otherwise, of appearance in care. The article
      forms part of the background to an ESRC-funded empirical study exploring the role
      of clothing and dress in the everyday lives of people with dementia, living at
      home or in care homes, and of their relatives. 

PMID- 24336856
TI  - Mixing methods to explore appearance in dementia care.
AB  - This paper considers approaches to investigating appearance and the work invested
      in maintaining it within dementia care. Our focus is upon methodological and
      methods-related issues associated with the challenge of generating knowledge of
      the embodied worlds of people with dementia. We begin with a brief overview of
      the literature on appearance and dementia, and consider what it teaches us about
      the nature of appearance and ways of understanding it. We describe and discuss
      the mixing of methods for an on-going investigation into hairdressing in dementia
      care: The Hair and Care project. Based upon the experience of research in care
      based hair salons, we argue for a creative use of methods in dementia studies as
      an avenue to better engaging with the embodied experiences of people with
      dementia and, as a result, understanding how people use their bodies and senses
      to create meaningful worlds. 

PMID- 24336857
TI  - 'Y' feel me?' How do we understand the person with dementia?
AB  - As dementia progresses problems of understanding emerge. Eventually spoken
      language can be lost. And yet, even into the severer stages of dementia, close
      carers can often understand the person in a variety of ways. Loss of language is
      not just a practical problem. It raises philosophical issues too. As Wittgenstein
      suggested, understanding entails grasping a form of life. Our understanding of
      agitated, pacing behaviour is similarly based on a unique history, on culture, on
      context. Hence, a philosophy gestures at the foundations of care. There is the
      potential to feel the person's meaning, even when it cannot be spoken. This is
      not simply by means of an alternative to language. The philosophy suggests that
      our engagement with the person is through and through. Understanding anyone is
      more like an aesthetic judgement than a cognitive act. 

PMID- 24336859
TI  - Embodiment: the implications for living well with dementia.

PMID- 24336858
TI  - Storytelling in dementia: embodiment as a resource.
AB  - In narrative research about persons with dementia, much research focuses on
      individual storytellers and their stories often stressing the discursive or
      textual aspects of stories. As persons with Alzheimer's disease generally have
      difficulties in telling stories according to often implicit narrative norms, they
      may appear to be less competent and agentive than what is actually the case. In
      the article, I argue for a change of focus from the textual aspects of narratives
      and the story as a product, to a focus on performative aspects and the embodied
      aspects of storytelling. A focus on the storytelling activity implies a change
      from the individual storyteller to the interaction with other participants in the
      storytelling situation. Drawing on two particular cases of storytelling, I stress
      the collaborative and embodied aspects of storytelling and argue that embodiment
      is less an individual expressive phenomenon than it is an interactive resource. 

PMID- 24336860
TI  - The chiral magnetic nanomotors.
AB  - Propulsion of chiral magnetic nanomotors powered by a rotating magnetic field is
      in the focus of the modern biomedical applications. This technology relies on
      strong interactions of dynamic and magnetic degrees of freedom of the system.
      Here we study in detail various experimentally observed regimes of the helical
      nanomotor orientation and propulsion depending on the actuation frequency, and
      establish the relation of these two properties to the remanent magnetization and
      geometry of the helical nanomotors. The theoretical predictions for the
      transition between the regimes and nanomotor orientation and propulsion speed are
      in excellent agreement with available experimental data. The proposed theory
      offers a few simple guidelines towards the optimal design of the magnetic
      nanomotors. 

PMID- 24336861
TI  - Cholesterol testing on a smartphone.
AB  - Home self-diagnostic tools for blood cholesterol monitoring have been around for
      over a decade but their widespread adoption has been limited by the relatively
      high cost of acquiring a quantitative test-strip reader, complicated procedure
      for operating the device, and inability to easily store and process results. To
      address this we have developed a smartphone accessory and software application
      that allows for the quantification of cholesterol levels in blood. Through a
      series of human trials we demonstrate that the system can accurately quantify
      total cholesterol levels in blood within 60 s by imaging standard test strips. In
      addition, we demonstrate how our accessory is optimized to improve measurement
      sensitivity and reproducibility across different individual smartphones. With the
      widespread adoption of smartphones and increasingly sophisticated image
      processing technology, accessories such as the one presented here will allow
      cholesterol monitoring to become more accurate and widespread, greatly improving
      preventive care for cardiovascular disease. 

PMID- 24336863
TI  - Range expansion of house sparrows (Passer domesticus) in Kenya: evidence of
      genetic admixture and human-mediated dispersal.
AB  - Introduced species offer an opportunity to study the ecological process of range
      expansions. Recently, 3 mechanisms have been identified that may resolve the
      genetic paradox (the seemingly unlikely success of introduced species given the
      expected reduction in genetic diversity through bottlenecks or founder effects):
      multiple introductions, high propagule pressure, and epigenetics. These
      mechanisms are probably also important in range expansions (either natural or
      anthropogenic), yet this possibility remains untested in vertebrates. We used
      microsatellite variation (7 loci) in house sparrows (Passer domesticus), an
      introduced species that has been spreading across Kenya for ~60 years, to
      determine if patterns of variation could explain how this human commensal
      overcame the genetic paradox and expresses such considerable phenotypic
      differentiation across this new range. We note that in some cases, polygenic
      traits and epistasis among genes, for example, may not have negative effects on
      populations. House sparrows arrived in Kenya by a single introduction event (to
      Mombasa, ~1950) and have lower genetic diversity than native European and
      introduced North American populations. We used Bayesian clustering of individuals
      (n = 233) to detect that at least 2 types of range expansion occurred in Kenya:
      one with genetic admixture and one with little to no admixture. We also found
      that genetic diversity increased toward a range edge, and the range expansion was
      consistent with long-distance dispersal. Based on these data, we expect that the
      Kenyan range expansion was anthropogenically influenced, as the expansions of
      other introduced human commensals may also be. 

PMID- 24336869
TI  - Can routinely collected ambulance data about assaults contribute to reduction in
      community violence?
AB  - BACKGROUND: The 'law of spatiotemporal concentrations of events' introduced major
      preventative shifts in policing communities. 'Hotspots' are at the forefront of
      these developments yet somewhat understudied in emergency medicine. Furthermore,
      little is known about interagency 'data-crossover', despite some developments
      through the Cardiff Model. Can police-ED interagency data-sharing be used to
      reduce community-violence using a hotspots methodology? METHODS: 12-month (2012)
      descriptive study and analysis of spatiotemporal clusters of police and emergency
      calls for service using hotspots methodology and assessing the degree of incident
      overlap. 3775 violent crime incidents and 775 assault incidents analysed using
      spatiotemporal clustering with k-means++ algorithm and Spearman's rho. RESULTS:
      Spatiotemporal location of calls for services to the police and the ambulance
      service are equally highly concentrated in a small number of geographical areas,
      primarily within intra-agency hotspots (33% and 53%, respectively) but across
      agencies' hotspots as well (25% and 15%, respectively). Datasets are
      statistically correlated with one another at the 0.57 and 0.34 levels, with 50%
      overlap when adjusted for the number of hotspots. At least one in every two
      police hotspots does not have an ambulance hotspot overlapping with it,
      suggesting half of assault spatiotemporal concentrations are unknown to the
      police. Data further suggest that more severely injured patients, as estimated by
      transfer to hospital, tend to be injured in the places with the highest number of
      police-recorded crimes. CONCLUSIONS: A hotspots approach to sharing data
      circumvents the problem of disclosing person-identifiable data between different
      agencies. Practically, at least half of ambulance hotspots are unknown to the
      police; if causal, it suggests that data sharing leads to both reduced community
      violence by way of prevention (such as through anticipatory patrols or problem
      oriented policing), particularly of more severe assaults, and improved efficiency
      of resource deployment.

PMID- 24336870
TI  - Thionoglycine as a multifunctional spectroscopic reporter of screw-sense
      preference in helical foldamers.
AB  - A single thionoglycine (glycine thioamide, -HNCH2C(=S)-) residue inserted into a
      peptide foldamer provides both a pair of germinal protons for use as a (1)H NMR
      stereochemical probe and a chromophore giving rise to a well defined Cotton
      effect in CD. Comparison of the response of these two features to a local
      helically chiral environment validates them as independent methods for
      quantifying the conformational screw-sense preference of a helical oligomer, in
      this case a peptide made of repeated Aib units. The sign of the Cotton effect
      provides a measure of the sign of the screw-sense preference, while both the
      chemical shift separation of the anisochronous signals of the glycine CH2 group
      and the magnitude of the Cotton effect give an estimate of the helicity excess of
      the oligomer. The thionoglycine unit is readily introduced synthetically by a
      thionation of a BocGlyAibOMe dipeptide.

PMID- 24336872
TI  - The microfluidic post-array device: high throughput production of single emulsion
      drops.
AB  - We present a microfluidic device that enables high throughput production of
      relatively monodisperse emulsion drops while controlling the average size. The
      device consists of a two-dimensional array of regularly-spaced posts. Large drops
      of a highly polydisperse crude emulsion are input into the device and are
      successively split by the posts, ultimately yielding a finer emulsion consisting
      of smaller, and much more monodisperse drops. The size distribution of the
      resultant emulsion depends only weakly on the viscosities of the input fluids and
      allows fluids of very high viscosities to be used. The average size and
      polydispersity of the drops depend strongly on the device geometry enabling both
      control and optimization. We use this device to produce drops of a highly viscous
      monomer solution and subsequently solidify them into polymeric microparticles.
      The production rate of these devices is similar to that achieved by membrane
      emulsification techniques, yet the control over the drop size is superior; thus
      these post-array microfluidic devices are potentially useful for industrial
      applications. 

PMID- 24336871
TI  - Tissue factor/factor VIIa induces cell survival and gene transcription by
      transactivation of the insulin-like growth factor 1 receptor.
AB  - The insulin-like growth factor 1 receptor (IGF-1R) is known to promote survival
      and has also been implicated in the pathogenesis of several disease states,
      including cardiovascular disorders and cancer. Recently, we showed that binding
      of coagulation factor VIIa (FVIIa) to its receptor tissue factor (TF) protects
      cancer cells from TNF-related apoptosis inducing ligand (TRAIL)-induced
      apoptosis. Here we present evidence that this biological function of TF/FVIIa is
      dependent on the IGF-1R. IGF-1R inhibitors AG1024 and PPP as well as siRNA
      mediated downregulation of IGF-1R, abolished the TF/FVIIa-mediated protection
      against TRAIL-induced apoptosis. Moreover, FVIIa rapidly induced a time- and
      concentration-dependent tyrosine phosphorylation of the IGF-1R in MDA-MB-231
      breast cancer cells and in primary human monocytes, an event that was accompanied
      by IGF-1R chromatin binding and gene transcription. We hereby present novel
      evidence of a cross-talk between the coagulation and IGF-1R signalling systems,
      and propose that the IGF-1R is a key player in mediating TF/FVIIa-induced cell
      survival. 

PMID- 24336873
TI  - High efficiency electrospun TiO2 nanofiber based hybrid organic-inorganic
      perovskite solar cell.
AB  - The good electrical and morphological characteristics of TiO2 nanofibers and the
      high extinction coefficient of CH3NH3PbI3 perovskite are combined to obtain a
      solar cell with a power conversion efficiency of 9.8%. The increase of the film
      thickness dramatically diminishes the performance due to the reduction in
      porosity of the TiO2 nanofiber framework. The optimum device (~413 nm film
      thickness) is compared to a planar device, where the latter produces higher V(oc)
      but lower J(sc), and consequently lower efficiency at all measured light
      intensities.

PMID- 24336874
TI  - Photofunctional host-guest hybrid materials and thin films of lanthanide
      complexes covalently linked to functionalized zeolite A.
AB  - Eight host-guest assemblies of zeolite A (ZA) and their thin films have been
      synthesized. The assembly of zeolite A was prepared by first embedding lanthanide
      complexes (Eu(TTA)n or Tb(TAA)n) into the cages of zeolite A and then grafting
      lanthanide complexes (Eu(L) or Tb(L), L = bipy or phen) onto the surface of
      functionalized zeolite A via 3-(methacryloyloxy)propyltrimethoxysilane (gamma
      MPS). The obtained organic-inorganic hybrid materials were investigated by means
      of XRD, FT-IR, SEM and luminescence spectroscopy. Firstly, the dependence of the
      crystal stability of zeolite A as the host of lanthanide complexes on the level
      of ion exchange was studied by XRD. The results indicated the degradation and
      partial collapse of zeolite A framework occurred upon doping with high amounts of
      lanthanide complexes into its channels. The integrity of zeolite A's framework
      was well maintained after fabrication through careful control of the ion-exchange
      extent. Secondly, the thin films of zeolite A assemblies obtained this way have
      the properties of homogeneous dense packing and a high degree of coverage of the
      crystals on the ITO glass, as shown in SEM images. Thirdly, the luminescence
      behavior of all the materials were investigated in detail. Among them, four white
      light-emitting materials from a three-component system that comprises a blue
      emitting zeolite A matrix, a red-emitting europium complex and a green-emitting
      terbium complex were obtained. 

PMID- 24336862
TI  - The Global Invertebrate Genomics Alliance (GIGA): developing community resources
      to study diverse invertebrate genomes.
AB  - Over 95% of all metazoan (animal) species comprise the "invertebrates," but very
      few genomes from these organisms have been sequenced. We have, therefore, formed
      a "Global Invertebrate Genomics Alliance" (GIGA). Our intent is to build a
      collaborative network of diverse scientists to tackle major challenges (e.g.,
      species selection, sample collection and storage, sequence assembly, annotation,
      analytical tools) associated with genome/transcriptome sequencing across a large
      taxonomic spectrum. We aim to promote standards that will facilitate comparative
      approaches to invertebrate genomics and collaborations across the international
      scientific community. Candidate study taxa include species from Porifera,
      Ctenophora, Cnidaria, Placozoa, Mollusca, Arthropoda, Echinodermata, Annelida,
      Bryozoa, and Platyhelminthes, among others. GIGA will target 7000
      noninsect/nonnematode species, with an emphasis on marine taxa because of the
      unrivaled phyletic diversity in the oceans. Priorities for selecting
      invertebrates for sequencing will include, but are not restricted to, their
      phylogenetic placement; relevance to organismal, ecological, and conservation
      research; and their importance to fisheries and human health. We highlight
      benefits of sequencing both whole genomes (DNA) and transcriptomes and also
      suggest policies for genomic-level data access and sharing based on transparency
      and inclusiveness. The GIGA Web site (http://giga.nova.edu) has been launched to
      facilitate this collaborative venture. 

PMID- 24336876
TI  - Editorial: science or fishing?

PMID- 24336875
TI  - Participatory arts for older adults: a review of benefits and challenges.
AB  - This article reviews the scientific literature on the enhancement of healthy
      aging in older adults through active participation in the arts. Methodologies and
      conclusions are described for studies of dance, expressive writing, music
      (singing and instrumental), theatre arts, and visual arts including documentation
      of mental/physical improvements in memory, creativity, problem solving, everyday
      competence, reaction time, balance/gait, and quality of life. In addition to
      these gains in measures of successful aging, the article also provides (in a
      Supplementary Appendix) some selected examples of arts engagement for remedial
      purposes. Finally, it offers suggestions for expanding inquiry into this
      underinvestigated corner of aging research. 

PMID- 24336877
TI  - Reconstruction of the ancestral plastid genome in Geraniaceae reveals a
      correlation between genome rearrangements, repeats, and nucleotide substitution
      rates.
AB  - Geraniaceae plastid genomes are highly rearranged, and each of the four genera
      already sequenced in the family has a distinct genome organization. This study
      reports plastid genome sequences of six additional species, Francoa sonchifolia,
      Melianthus villosus, and Viviania marifolia from Geraniales, and Pelargonium
      alternans, California macrophylla, and Hypseocharis bilobata from Geraniaceae.
      These genome sequences, combined with previously published species, provide
      sufficient taxon sampling to reconstruct the ancestral plastid genome
      organization of Geraniaceae and the rearrangements unique to each genus. The
      ancestral plastid genome of Geraniaceae has a 4 kb inversion and a reduced,
      Pelargonium-like small single copy region. Our ancestral genome reconstruction
      suggests that a few minor rearrangements occurred in the stem branch of
      Geraniaceae followed by independent rearrangements in each genus. The genomic
      comparison demonstrates that a series of inverted repeat boundary shifts and
      inversions played a major role in shaping genome organization in the family. The
      distribution of repeats is strongly associated with breakpoints in the rearranged
      genomes, and the proportion and the number of large repeats (>20 bp and >60 bp)
      are significantly correlated with the degree of genome rearrangements. Increases
      in the degree of plastid genome rearrangements are correlated with the
      acceleration in nonsynonymous substitution rates (dN) but not with synonymous
      substitution rates (dS). Possible mechanisms that might contribute to this
      correlation, including DNA repair system and selection, are discussed. 

PMID- 24336878
TI  - Reduced nuclear genomes maintain high gene transcription levels.
AB  - Reductive genome evolution is seen in organisms living in close association with
      each other, such as in endosymbiosis, symbiosis, and parasitism. The reduced
      genomes of endosymbionts and parasites often exhibit similar features such as
      high gene densities and A+T compositional bias. Little is known about how the
      regulation of gene expression has been affected in organisms with highly
      compacted genomes. We studied gene transcription patterns in "nucleomorph"
      genomes, which are relic nuclear genomes of algal endosymbionts found in
      cryptophytes and chlorarachniophytes. We examined nuclear and nucleomorph gene
      transcription patterns using RNA-Seq transcriptome and genome mapping analyses in
      representatives of both lineages. In all four examined genomes, the most highly
      transcribed nucleomorph gene category was found to be plastid-associated genes.
      Remarkably, only 0.49-3.37% of the nucleomorph genomes of these organisms did not
      have any mRNA counterpart in our RNA-Seq data sets, and nucleomorph genes show
      equal or higher levels of transcription than their counterparts in the nuclear
      genomes. We hypothesize that elevated levels of nucleomorph gene transcription
      may serve to counteract the degradation or modification of protein function due
      to the loss of interacting proteins in the nucleomorph and nucleomorph-associated
      subcellular compartments. 

PMID- 24336879
TI  - Enhancement of satellite cell differentiation and functional recovery in injured
      skeletal muscle by hyperbaric oxygen treatment.
AB  - Recently, the use of hyperbaric oxygen (HBO) treatments by elite athletes to
      accelerate recovery from muscle injuries has become increasingly popular.
      However, the mechanism of promoting muscle regeneration under HBO conditions has
      not yet been defined. In this study, we investigated whether HBO treatments
      promoted muscle regeneration and modulated muscle regulatory factor expression in
      a rat skeletal muscle injury model. Muscle injury was induced by injecting
      cardiotoxin (CTX) into the tibialis anterior (TA) muscles. As the HBO treatment,
      rats were placed in an animal chamber with 100% oxygen under 2.5 atmospheres
      absolute for 2 h/day, 5 days/wk for 2 wk. We then performed histological
      analyses, measured the maximum force-producing capacity of the regenerating
      muscle fibers, and performed quantitative RT-PCR analysis of muscle regulatory
      factor mRNAs. The cross-sectional areas and maximum force-producing capacity of
      the regenerating muscle fibers were increased by HBO treatment after injury. The
      mRNA expression of MyoD, myogenin, and IGF-1 increased significantly in the HBO
      group at 3 and 5 days after injury. The number of Pax7(+)/MyoD(+), Pax7(
      )/MyoD(+), and Pax7(+)/BrdU(+)-positive nuclei was increased by HBO treatment. In
      this study, we demonstrated that HBO treatment accelerated satellite cell
      proliferation and myofiber maturation in rat muscle that was injured by a CTX
      injection. These results suggest that HBO treatment accelerates healing and
      functional recovery after muscle injury.

PMID- 24336880
TI  - Pulmonary surfactant synthesis after unilateral lung injury in mice.
AB  - Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a
      murine model of unilateral aspiration to compare surfactant synthesis in the
      injured (I) and noninjured (NI) contralateral lung. Mice were instilled with
      hydrochloric acid in the right bronchus and, after 18 h, an intraperitoneal dose
      of deuterated water was administered as precursor of disaturated
      phosphatidylcholine (DSPC)-palmitate. Selected bronchoalveolar lavage fluid
      (BALF) was collected at scheduled time points and lungs were removed. We measured
      DSPC-palmitate synthesis in lung tissue and secretion in BALF by gas
      chromatography-isotope ratio mass spectrometry, together with total proteins and
      myeloperoxidase activity (MPO) by spectrophotometry. BALF total proteins and MPO
      were significantly increased in the I lungs compared with NI and naive control
      lungs. The DSPC pool size was significantly lower in the BALF of the I lungs
      compared with naive controls. DSPC synthesis was accelerated in the I and NI
      lungs. DSPC secretion of the I lungs was similar to their respective naive
      controls, and it was markedly lower compared with their respective NI
      contralateral lungs. DSPC synthesis and secretion were faster, especially in the
      NI lungs, compared with naive control lungs, as a possible compensatory mechanism
      due to a cross-talk between the lungs triggered by inflammation,
      hyperventilation, and/or undetermined type II cell reaction to the injury. 

PMID- 24336882
TI  - Effect of age on the hemodynamic and sympathetic responses at the onset of
      isometric handgrip exercise.
AB  - Cardiac and peripheral vasomotor factors contribute to the rapid pressor response
      at the onset of isometric handgrip exercise. We tested the hypothesis that age
      enhances the sympathetic and vasoconstrictor response at the onset of isometric
      handgrip exercise so that the pressor response is maintained, despite a
      diminished cardiac function. Twelve young and twelve older (24 +/- 3 and 63 +/- 8
      yr) individuals performed 20-s isometric handgrip exercise at 30, 40, or 50% of
      maximal voluntary contraction force. Muscle sympathetic nerve activity (MSNA) was
      measured using microneurography. Mean arterial pressure (MAP) and cardiac output
      (Q) were assessed continuously by finger plethysmography and total peripheral
      resistance was calculated. MAP increased with the onset of handgrip; this
      increase was associated with handgrip intensity and was similar in both groups.
      Heart rate and Q increased with increasing handgrip intensity in both groups, but
      increases were greater in young vs. older individuals (age * handgrip intensity
      interaction, P < 0.05). MSNA burst frequency increased (P < 0.01), while MSNA
      burst incidence tended to increase (P = 0.06) with increasing handgrip intensity
      in both groups. The change in MSNA between baseline and handgrip, for both
      frequency and incidence, increased with increasing handgrip intensity for both
      groups. There was no effect of handgrip intensity or age on total peripheral
      resistance. The smaller heart rate and Q response during the first 20 s of
      handgrip exercise in older individuals was not accompanied by a greater
      sympathetic activation or vasoconstrictor response. However, increases in MAP
      were similar between groups, indicating that the pressor response at the onset of
      handgrip exercise is preserved with aging. 

PMID- 24336881
TI  - HIF and pulmonary vascular responses to hypoxia.
AB  - In the lung, acute reductions in oxygen lead to hypoxic pulmonary
      vasoconstriction, whereas prolonged exposures to hypoxia result in sustained
      vasoconstriction, pulmonary vascular remodeling, and the development of pulmonary
      hypertension. Data from both human subjects and animal models implicate a role
      for hypoxia-inducible factors (HIFs), oxygen-sensitive transcription factors, in
      pulmonary vascular responses to both acute and chronic hypoxia. In this review,
      we discuss work from our laboratory and others supporting a role for HIF in
      modulating hypoxic pulmonary vasoconstriction and mediating hypoxia-induced
      pulmonary hypertension, identify some of the downstream targets of HIF, and
      assess the potential to pharmacologically target the HIF system. 

PMID- 24336883
TI  - Mitochondrial uncoupling reduces exercise capacity despite several skeletal
      muscle metabolic adaptations.
AB  - The effects of mitochondrial uncoupling on skeletal muscle mitochondrial
      adaptation and maximal exercise capacity are unknown. In this study, rats were
      divided into a control group (CTL, n = 8) and a group treated with 2,4
      dinitrophenol, a mitochondrial uncoupler, for 28 days (DNP, 30 mg.kg(-1).day(-1)
      in drinking water, n = 8). The DNP group had a significantly lower body mass (P <
      0.05) and a higher resting oxygen uptake (Vo2, P < 0.005). The incremental
      treadmill test showed that maximal running speed and running economy (P < 0.01)
      were impaired but that maximal Vo2 (Vo2max) was higher in the DNP-treated rats (P
      < 0.05). In skinned gastrocnemius fibers, basal respiration (V0) was higher (P <
      0.01) in the DNP-treated animals, whereas the acceptor control ratio (ACR,
      Vmax/V0) was significantly lower (P < 0.05), indicating a reduction in OXPHOS
      efficiency. In skeletal muscle, DNP activated the mitochondrial biogenesis
      pathway, as indicated by changes in the mRNA expression of PGC1-alpha and -beta,
      NRF-1 and -2, and TFAM, and increased the mRNA expression of cytochrome oxidase 1
      (P < 0.01). The expression of two mitochondrial proteins (prohibitin and Ndufs 3)
      was higher after DNP treatment. Mitochondrial fission 1 protein (Fis-1) was
      increased in the DNP group (P < 0.01), but mitofusin-1 and -2 were unchanged.
      Histochemical staining for NADH dehydrogenase and succinate dehydrogenase
      activity in the gastrocnemius muscle revealed an increase in the proportion of
      oxidative fibers after DNP treatment. Our study shows that mitochondrial
      uncoupling induces several skeletal muscle adaptations, highlighting the role of
      mitochondrial coupling as a critical factor for maximal exercise capacities.
      These results emphasize the importance of investigating the qualitative aspects
      of mitochondrial function in addition to the amount of mitochondria. 

PMID- 24336884
TI  - Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood
      flow during visual stimulation.
AB  - The carbonic anhydrase (CA) inhibitor acetazolamide (AZ) is used routinely to
      estimate cerebrovascular reserve capacity in patients, as it reliably increases
      cerebral blood flow (CBF). However, the mechanism by which AZ accomplishes this
      CBF increase is not entirely understood. We recently discovered that CA can
      produce nitric oxide (NO) from nitrite, and that AZ enhances this NO production
      in vitro. In fact, this interaction between AZ and CA accounted for a large part
      of AZ's vasodilatory action, which fits well with the known vasodilatory potency
      of NO. The present study aimed to assess whether AZ acts similarly in vivo in the
      human cerebrovascular system. Hence, we increased or minimized the dietary intake
      of nitrate in 20 healthy male participants, showed them a full-field flickering
      dartboard, and measured their CBF response to this visual stimulus with arterial
      spin labeling. Doing so, we found a significant positive interaction between the
      dietary intake of nitrate and the CBF modulation afforded by AZ during visual
      stimulation. In addition, but contrary to studies conducted in elderly
      participants, we report no effect of nitrate intake on resting CBF in healthy
      human participants. The present study provides in vivo support for an enhancing
      effect of AZ on the NO production from nitrite catalyzed by CA in the
      cerebrovascular system. Furthermore, our results, in combination with the results
      of other groups, indicate that nitrate may have significant importance to
      vascular function when the cerebrovascular system is challenged by age or
      disease. 

PMID- 24336885
TI  - Timing of return from altitude training for optimal sea level performance.
AB  - While a number of published studies exist to guide endurance athletes with the
      best practices regarding implementation of altitude training, a key unanswered
      question concerns the proper timing of return to sea level prior to major
      competitions. Evidence reviewed here suggests that, altogether, the
      deacclimatization responses of hematological, ventilatory, and biomechanical
      factors with return to sea level likely interact to determine the best timing for
      competitive performance. 

PMID- 24336887
TI  - Hospital report cards: necessary but not sufficient?

PMID- 24336888
TI  - Structure and dynamics of CO2 and N2 in a tetracyanoborate based ionic liquid.
AB  - To gain insight into the transport behavior of gas molecules such as CO2versus N2
      through ionic liquid membranes, we performed molecular dynamics simulations to
      investigate the structure and dynamics of CO2 and N2 gases in a tetracyanoborate
      based ionic liquid recently shown to exhibit high CO2/N2 permselectivity. We
      found that upon addition of CO2 or N2 the liquid structure does not change. CO2
      or N2 molecules occupy the voids between ions and their local environments are
      found to be similar. Gas diffusivity is about one order of magnitude greater than
      that of the cation or anion. Dissolved N2 diffuses slightly faster than CO2. We
      hence conclude that the high permeability selectivity of CO2versus N2 observed
      experimentally is mainly due to the disparity in gas solubility. In other words,
      the much higher solubility of CO2 in tetracyanoborate-based ionic liquids such as
      1-ethyl-3-methylimidazolium tetracyanoborate [emimB(CN)4] leads to their high CO2
      permeability. Based on the experimental solubility and the simulated diffusivity,
      we obtained a permeability of 2830 barrer for CO2 in emimB(CN)4 at 300 K, in good
      agreement with the experimental value of 2040 barrer. 

PMID- 24336886
TI  - Ventilatory long-term facilitation is evident after initial and repeated exposure
      to intermittent hypoxia in mice genetically depleted of brain serotonin.
AB  - Our study was designed to determine if central nervous system (CNS) serotonin is
      required for the induction of ventilatory long-term facilitation (LTF) in intact,
      spontaneously breathing mice. Nineteen tryptophan hydroxylase 2-deficient (Tph2(
      /-)) mice, devoid of serotonin in the CNS, and their wild-type counterparts
      (Tph2(+/+)) were exposed to intermittent hypoxia each day for 10 consecutive
      days. The ventilatory response to intermittent hypoxia was greater in the
      Tph2(+/+) compared with the Tph2(-/-) mice (1.10 +/- 0.10 vs. 0.77 +/- 0.01 ml
      min(-1).percent(-1) oxygen; P <= 0.04). Ventilatory LTF, caused by increases in
      breathing frequency, was evident in Tph2(+/+) and Tph2(-/-) mice following
      exposure to intermittent hypoxia each day; however, the magnitude of the response
      was greater in the Tph2(+/+) compared with the Tph2(-/-) mice (1.11 +/- 0.02 vs.
      1.05 +/- 0.01 normalized to baseline on each day; P <= 0.01). The magnitude of
      ventilatory LTF increased significantly from the initial to the finals days of
      the protocol in the Tph2(-/-) (1.06 +/- 0.02 vs. 1.11 +/- 0.03 normalized to
      baseline on the initial days; P <= 0.004) but not in the Tph2(+/+) mice. This
      enhanced response was mediated by increases in tidal volume. Body temperature and
      metabolic rate did not account for differences in the magnitude of ventilatory
      LTF observed between groups after acute and repeated daily exposure to
      intermittent hypoxia. We conclude that ventilatory LTF, after acute exposure to
      intermittent hypoxia, is mediated by increases in breathing frequency and occurs
      in the absence of serotonin, although the magnitude of the response is
      diminished. This weakened response is enhanced following repeated daily exposure
      to intermittent hypoxia, via increases in tidal volume, to a similar magnitude
      evident in Tph2(+/+) mice. Thus the magnitude of ventilatory LTF following
      repeated daily exposure to intermittent hypoxia is not dependent on the presence
      of CNS serotonin. 

PMID- 24336889
TI  - Thermodynamics of interfacial changes in a protein-protein complex.
AB  - Recent experiments with biomacromolecular complexes suggest that structural
      modifications at the interfaces are vital for stability of the complexes and the
      functions of the biomacromolecules. Although several qualitative aspects about
      such interfaces are known from structural data, quantification of the interfacial
      changes is lacking. In this work, we study the thermodynamic changes at the
      interface in the complex between an enzyme, Nuclease A (NucA), and a specific
      inhibitor protein, NuiA. We calculate the conformational free energy and
      conformational entropy costs from histograms of the dihedral angles generated
      from all-atom molecular dynamics simulations on the complex and the free
      proteins. We extract the conformational thermodynamic parameters for changes in
      the tertiary structure of NuiA. We show that the binding is dominated by the
      interfacial changes, where the basic residues of NucA and acidic residues of NuiA
      are highly ordered and stabilized via strong electrostatic interactions. Our
      results correlate well with known information from structural studies. The tight
      interfacial structure is reflected in the significant changes in the structure
      and dynamics of the water molecules at the enzyme-inhibitor interface. The
      interfacial water molecules contribute significantly to the entropy loss for the
      overall complexation. 

PMID- 24336890
TI  - Sorting of large-diameter semiconducting carbon nanotube and printed flexible
      driving circuit for organic light emitting diode (OLED).
AB  - A novel approach was developed to sort a large-diameter semiconducting single
      walled carbon nanotube (sc-SWCNT) based on copolyfluorene derivative with high
      yield. High purity sc-SWCNTs inks were obtained by wrapping arc-discharge SWCNTs
      with poly[2,7-(9,9-dioctylfluorene)-alt-4,7-bis(thiophen-2-yl)benzo-2,1,3
      thiadiazole] (PFO-DBT) aided by sonication and centrifugation in tetrahydrofuran
      (THF). The sorted sc-SWCNT inks and nanosilver inks were used to print top-gated
      thin-film transistors (TFTs) on flexible substrates with an aerosol jet printer.
      The printed TFTs demonstrated low operating voltage, small hysteresis, high on
      state current (up to 10(-3) A), high mobility and on-off ratio. An organic light
      emitting diode (OLED) driving circuit was constructed based on the printed TFTs,
      which exhibited high on-off ratio up to 10(4) and output current up to 3.5 * 10(
      4) A at V(scan) = -4.5 V and Vdd = 0.8 V. A single OLED was switched on with the
      driving circuit, showing the potential as backplanes for active matrix OLED
      applications.

PMID- 24336892
TI  - Novel near-IR absorbing phenyl-substituted phthalo- and naphthalocyanine
      complexes of lanthanide(III): synthesis and spectral and electrochemical
      properties.
AB  - A series of novel phenyl-substituted planar and sandwich-type complexes of Eu, Er
      and Lu with phthalo and naphthalocyanine ligands was obtained. A successful
      synthesis of dinaphthalocyanines from the ligand is described. A selective
      synthetic approach to the phenyl-substituted triphthalocyanine complexes from the
      ligand and acetylacetonate salts of lanthanides was developed. Correlations
      between the ionic radii of the central metal and absorption maxima were obtained
      for sandwich-type complexes. It was found that intervalence (IV) bands for
      dinaphthalocyanine complexes were red-shifted about 200 nm in comparison with
      corresponding diphthalocyanines, reaching 1797 nm for the Eu complex. The
      electrochemical behaviour of planar and sandwich-type Lu complexes was
      investigated. For the first time a spectroelectrochemical study of multistep
      reduction and oxidation processes for a triple-decker complex was carried out
      using the example of the triphthalocyanine of Lu. The structures of the compounds
      obtained were determined by (1)H NMR and high resolution MALDI TOF/TOF. The first
      single-crystal structure for an aryl-substituted double-decker complex was
      described using the example of the diphthalocyanine of Lu, showing the presence
      of intramolecular pi-pi interactions between phenyl groups. 

PMID- 24336891
TI  - Fractalkine promotes platelet activation and vascular dysfunction in congestive
      heart failure.
AB  - Endothelial dysfunction and enhanced platelet reactivity in congestive heart
      failure (CHF) contribute to poor prognosis. CHF patients display an impaired
      responsiveness to clopidogrel. Fractalkine activates platelets and elevated
      plasma levels of this chemokine are a feature of CHF. We here addressed the
      interrelation of fractalkine, platelet reactivity and clopidogrel efficacy in
      humans and rats with CHF. Fractalkine serum levels determined by ELISA were
      increased in CHF patients (CHF: 1548 +/- 650 pg/ml; CONTROL: 968 +/- 575 pg/ml,
      p<0.01) and following CHF induction in rats (CHF: 1509 +/- 753 pg/ml; Sham: 1181
      +/- 275 pg/ml, p<0.05). Expression of fractalkine and its receptor CX3CR1 was
      enhanced in aortas of CHF rats as determined by immunofluorescence microscopy and
      molecular analysis. Fractalkine significantly aggravated endothelial dysfunction
      and augmented P-selectin expression on platelets from CHF rats. Platelet surface
      expression of CX3CR1 was increased in CHF rats, who displayed an impaired
      response to clopidogrel (platelet reactivity to ADP: CHF 30 +/- 22%; Sham: 8 +/-
      5%, p<0.05). Similarly in humans with CHF, elevated fractalkine levels were
      accompanied by reduced clopidogrel responsiveness. Patients with high on
      clopidogrel treatment platelet P2Y12 reactivity displayed higher fractalkine
      levels (1525 +/- 487 pg/ml) than those with sufficient clopidogrel response (684
      +/- 315 pg/ml, p<0.01). In conclusion, in CHF fractalkine was increased on the
      endothelium and in blood serum, and platelet surface-expression of CX3CR1 was
      enhanced. Fractalkine diminished endothelial function beyond the impairment
      already observed in CHF and was associated with a reduced responsiveness to the
      platelet inhibitor clopidogrel. These findings may indicate a novel
      pathophysiological mechanism contributing to impaired clopidogrel responsiveness
      in CHF.

PMID- 24336893
TI  - Size-dependent magnetic order and giant magnetoresistance in organic titanium
      benzene multidecker cluster.
AB  - Using density functional theory and non-equilibrium Green's function method, we
      investigated the magnetic and transport properties of small organic titanium
      benzene sandwich clusters TinBzn+1 (n = 1-3). The results show that TiBz2 is
      nonmagnetic while Ti2Bz3 and Ti3Bz4 are ferromagnetic, and our prediction is in
      agreement with experimental observation. The double exchange mechanism plays a
      key role in the ferromagnetism of larger clusters. With Ni as the two electrodes,
      significant spin-filter efficiency (SFE) and giant magnetoresistance (GMR) were
      found in the TinBzn+1 molecular junction. These transport properties could be
      controlled by cluster size, bias voltage or gate voltage. Specially, a sign
      reversible GMR effect was observed in the Ti2Bz3 molecular junction. Finally, the
      microscopic mechanisms of SFE and GMR were suggested. 

PMID- 24336894
TI  - Epidural analgesia in laparoscopic colorectal surgery: a nationwide analysis of
      use and outcomes.
AB  - IMPORTANCE: The use of epidural analgesia in laparoscopic colorectal surgery has
      demonstrated superiority over conventional analgesia in controlling pain.
      Controversy exists, however, regarding its cost-effectiveness and its effect on
      postoperative outcomes. OBJECTIVES: To examine the use of epidural analgesia in
      laparoscopic colorectal surgery at the national level and to compare its outcomes
      with those of conventional analgesia. DESIGN, SETTING, AND PARTICIPANTS: This is
      a retrospective review of laparoscopic colorectal cases performed with or without
      epidural analgesia for cancer, diverticular disease, and benign polyps. Patient
      demographic characteristics, disease and procedure types, and hospital settings
      were listed for patients in the epidural and conventional analgesia groups. A 1
      to 4 case-matched analysis was performed, matching for patient demographic
      characteristics, hospital setting, indications, and procedure type. Data were
      obtained from the Nationwide Inpatient Sample between January 1, 2002, and
      December 31, 2010. MAIN OUTCOMES AND MEASURES: Total hospital charge, length of
      stay, mortality, pneumonia, respiratory failure, urinary tract infection, urinary
      retention, anastomotic leak, and postoperative ileus. RESULTS: A total of 191576
      laparoscopic colorectal cases were identified during the study period. Epidural
      analgesia was used in 4102 cases (2.14%). Epidurals were more likely to be used
      in large teaching hospitals, cancer cases, and rectal operations. On case-matched
      analysis, epidural analgesia was associated with a longer hospital stay by 0.60
      day (P=.003), higher hospital charges by $3732.71 (P=.02), and higher rate of
      urinary tract infection (odds ratio=1.81; P=.05). Epidural analgesia did not
      affect the incidence of respiratory failure, pneumonia, anastomotic leak, ileus,
      or urinary retention. CONCLUSIONS AND RELEVANCE: The perioperative use of
      epidural analgesia in laparoscopic colorectal surgery is limited in the United
      States. While epidural analgesia appears to be safe, it comes with higher
      hospital charges, longer hospital stay, and a higher incidence of urinary tract
      infections.

PMID- 24336896
TI  - Gene expression scaled by distance to the genome replication site.
AB  - A simple mode of gene expression scaled by the distance from the chromosomal
      location of the gene to the genome replication site oriC was determined. The
      common formula representing the effect of genomic position on expression capacity
      not only supports the multifork replication model but also provides a base
      correlation for theoretical simulation and synthetic constructs. 

PMID- 24336897
TI  - N-alkyl pyrrolidone ether podands as versatile alkali metal ion chelants.
AB  - This work explores the coordination chemistry of a bis(pyrrolidone) ether ligand.
      Pyrrolidones are commercially important functional groups because of the high
      polarity and hence high hydrophilicity and surface affinity. An array of alkali
      metal ion complexes of a podand bearing two pendant pyrrolidone functionalities,
      namely 1-{2-[2-(2-oxo-pyrrolid-1-yl)-ethoxy]-ethyl}-pyrrolid-2-one (1) are
      reported. Reaction of this ligand with sodium hexafluorophosphate gives two
      discrete species of formulae [Na(1)2]PF6 (3) and [Na3(H2O)2(MU-1)2](PF6)3 (4),
      and a coordination polymer {[Na3(MU3-1)3(MU2-1)](PF6)3}n (5). The same reaction
      in methanol gives a 1 : 1 complex, namely [Na2(MU-1)2(MeOH)2](PF6)2 (6). Use of
      tetraphenyl borate as a less coordinating counter ion gives
      [Na2(1)2(H2O)4](BPh4)2 (7) and [Na2(1)4](BPh4)2 (8). Two potassium complexes have
      also been isolated, a monomer [K(1)2]PF6 (9) and a cyclic tetramer [K4(MU4
      H2O)2(MU-1)4](PF6)4 (10). The structures illustrate the highly polar nature of
      the amide carbonyl moiety within bis(pyrrolidone) ethers with longer interactions
      to the ether oxygen atom. The zinc complex is also reported and {[ZnCl2(MU-1)]}n
      (11) exhibits bonding only to the carbonyl moieties. The ether oxygen atom is not
      necessary for Na(+) complexation as exemplified by the structure of the sodium
      complex of the analogue 1,3-bis(pyrrolid-2-on-1-yl)butane (2). Reaction of
      compound 1 with lithium salts results in isolation of the protonated ligand.

PMID- 24336895
TI  - Parental diabetes and birthweight in 236 030 individuals in the UK biobank study.
AB  - BACKGROUND: The UK Biobank study provides a unique opportunity to study the
      causes and consequences of disease. We aimed to use the UK Biobank data to study
      the well-established, but poorly understood, association between low birthweight
      and type 2 diabetes. METHODS: We used logistic regression to calculate the odds
      ratio for participants' risk of type 2 diabetes given a one standard deviation
      increase in birthweight. To test for an association between parental diabetes and
      birthweight, we performed linear regression of self-reported parental diabetes
      status against birthweight. We performed path and mediation analyses to test the
      hypothesis that birthweight partly mediates the association between parental
      diabetes and participant type 2 diabetes status. RESULTS: Of the UK Biobank
      participants, 277 261 reported their birthweight. Of 257 715 individuals of White
      ethnicity and singleton pregnancies, 6576 had type 2 diabetes, 19 478 reported
      maternal diabetes (but not paternal), 20 057 reported paternal diabetes (but not
      maternal) and 2754 participants reported both parents as having diabetes. Lower
      birthweight was associated with type 2 diabetes in the UK Biobank participants. A
      one kilogram increase in birthweight was associated with a lower risk of type 2
      diabetes (odds ratio: 0.74; 95% CI: 0.71, 0.76; P = 2 * 10(-57)). Paternal
      diabetes was associated with lower birthweight (45 g lower; 95% CI: 36, 54; P = 2
      * 10(-23)) relative to individuals with no parental diabetes. Maternal diabetes
      was associated with higher birthweight (59 g increase; 95% CI: 50, 68; P = 3 *
      10(-37)). Participants' lower birthweight was a mediator of the association
      between reported paternal diabetes and participants' type 2 diabetes status,
      explaining 1.1% of the association, and participants' higher birthweight was a
      mediator of the association between reported maternal diabetes and participants'
      type 2 diabetes status, explaining 1.2% of the association. CONCLUSIONS: Data
      from the UK Biobank provides the strongest evidence by far that paternal diabetes
      is associated with lower birthweight, whereas maternal diabetes is associated
      with increased birthweight. Our findings with paternal diabetes are consistent
      with a role for the same genetic factors influencing foetal growth and type 2
      diabetes.

PMID- 24336898
TI  - Thrombin-induced platelet-fibrin clot strength: relation to high on-clopidogrel
      platelet reactivity, genotype, and post-percutaneous coronary intervention
      outcomes.
AB  - The relationship between thrombin-induced platelet-fibrin clot strength
      (MATHROMBIN), genotype and high on-treatment platelet reactivity (HPR) is
      unknown. The aim of this study is to assess the influence of MATHROMBIN measured
      by thrombelastography on HPR and long-term major adverse cardiovascular events
      (MACE) in percutaneous coronary intervention (PCI)-treated patients during
      aspirin and clopidogrel therapy. MATHROMBIN, platelet aggregation, genotype, and
      two-year MACE were assessed in 197 PCI-treated patients. HPR was defined as 5 uM
      ADP-induced PR >= 46% measured by conventional aggregometry. Both high
      MATHROMBIN(>= 68 mm) and CYP2C19*2 allele carriage were independently associated
      with ADP-induced platelet aggregation (beta coefficient: 8.3% and 12.0%,
      respectively). The combination of CYP2C19*2 allele carriage and high MATHROMBIN
      increased the predictive value for the risk of HPR (odds ratio: 13.89; 95%
      confidence interval: 3.41 to 55.56; p < 0.001). MACE occurred in 25 patients
      (12.7%). HPR and high MATHROMBIN were both associated with MACE (hazard ratio:
      3.09 and 2.24, respectively), and patients with both HPR and high MATHROMBIN
      showed an increased risk for MACE (adjusted hazard ratio: 5.56; 95% confidence
      interval: 1.85 to 16.67; p = 0.002). In conclusion, this is the first study to
      demonstrate that high platelet-fibrin clot strength is an independent determinant
      of HPR in PCI-treated patients. Combining the measurements of platelet
      aggregation and platelet-fibrin clot strength may enhance post-PCI risk
      stratification and deserves further study. 

PMID- 24336899
TI  - Highly sensitive free radical detection by nitrone-functionalized gold
      nanoparticles.
AB  - The detection of free radicals and related species has attracted significant
      attention in recent years because of their critical roles in physiological and
      pathological processes. Among the methods for the detection of free radicals,
      electron spin resonance (ESR) coupled with the use of the spin trapping technique
      has been an effective approach for characterization and quantification of these
      species due to its high specificity. However, its application in biological
      systems, especially in in vivo systems, has been greatly limited partially due to
      the low reaction rate between the currently available spin traps with biological
      radicals. To overcome this drawback, we herein report the first example of
      nitrone functionalized gold nanoparticles (Au@EMPO) as highly efficient spin
      traps in which the thiolated EMPO (2-(ethoxycarbonyl)-2-methyl-3,4-dihydro-2H
      pyrrole 1-oxide) derivative was self-assembled on gold nanoparticles. Kinetic
      studies showed that Au@EMPO has a 137-fold higher reaction rate constant with OH
      than PBN (N-tert-butyl-alpha-phenylnitrone). Owing to the high rate of trapping
      OH by Au@EMPO as well as the high stability of the resulting spin adduct (t1/2 ~
      56 min), Au@EMPO affords 124-fold higher sensitivity for OH than EMPO. Thus, this
      new nanospin trap shows great potential in trapping the important radicals such
      as OH in various biological systems and provides a novel strategy to design spin
      traps with much improved properties.

PMID- 24336900
TI  - Synthesis and catalytic alcohol oxidation and ketone transfer hydrogenation
      activity of donor-functionalized mesoionic triazolylidene ruthenium(II)
      complexes.
AB  - We report on the synthesis of a variety of C,E-bidentate triazolylidene ruthenium
      complexes that comprise different donor substituents E (E = C: phenyl anion; E =
      O: carboxylate, alkoxide; E = N: pyridine at heterocyclic carbon or nitrogen).
      Introduction of these donor functionalities is greatly facilitated by the
      synthetic versatility of triazoles, and their facile preparation routes. Five
      different complexes featuring a C,E-coordinated ruthenium center with
      chloride/cymene spectator ligands and three analogous solvento complexes with
      MeCN spectator ligands were prepared and evaluated as catalyst precursors for
      direct base- and oxidant-free alcohol dehydrogenation, and for transfer
      hydrogenation using basic iPrOH as a source of dihydrogen. In both catalytic
      reactions, the neutral/mono-cationic complexes with chloride/cymene spectator
      ligands performed better than the solvento ruthenium complexes. The donor
      functionality had a further profound impact on catalytic activity. For alcohol
      dehydrogenation, the C,C-bidentate phenyl-triazolylidene ligand induced highest
      conversions, while carboxylate or pyridine donor sites gave only moderate
      activity or none at all. In contrast, transfer hydrogenation is most efficient
      when a pyridyl donor group is linked to the triazolylidene via the heterocyclic
      carbon atom, providing turnover frequencies as high as 1400 h(-1) for
      cyclohexanone transfer hydrogenation. The role of the donor group is discussed in
      mechanistic terms. 

PMID- 24336901
TI  - Nasal dyspnea and intermittent epistaxis.

PMID- 24336902
TI  - Understanding the volume-outcome effect in cardiovascular surgery: the role of
      failure to rescue.
AB  - IMPORTANCE: To effectively guide interventions aimed at reducing mortality in low
      volume hospitals, the underlying mechanisms of the volume-outcome relationship
      must be further explored. Reducing mortality after major postoperative
      complications may represent one point along the continuum of patient care that
      could significantly affect overall hospital mortality. OBJECTIVE: To determine
      whether increased mortality at low-volume hospitals performing cardiovascular
      surgery is a function of higher postoperative complication rates or of less
      successful rescue from complications. DESIGN, SETTING, AND PARTICIPANTS: We used
      patient-level data from 119434 Medicare fee-for-service beneficiaries aged 65 to
      99 years undergoing coronary artery bypass grafting, aortic valve repair, or
      abdominal aortic aneurysm repair between January 1, 2005, and December 31, 2006.
      For each operation, we first divided hospitals into quintiles of procedural
      volume. We then assessed hospital risk-adjusted rates of mortality, major
      complications, and failure to rescue (ie, case fatality among patients with
      complications) within each volume quintile. EXPOSURE: Hospital procedural volume.
      MAIN OUTCOMES AND MEASURES: Hospital rates of risk-adjusted mortality, major
      complications, and failure to rescue. RESULTS: For each operation, hospital
      volume was more strongly related to failure-to-rescue rates than to complication
      rates. For example, patients undergoing aortic valve replacement at very low
      volume hospitals (lowest quintile) were 12% more likely to have a major
      complication than those at very high-volume hospitals (highest quintile) but were
      57% more likely to die if a complication occurred. CONCLUSIONS AND RELEVANCE:
      High-volume and low-volume hospitals performing cardiovascular surgery have
      similar complication rates but disparate failure-to-rescue rates. While
      preventing complications is important, hospitals should also consider
      interventions aimed at quickly recognizing and managing complications once they
      occur.

PMID- 24336903
TI  - Theoretical studies on beta and delta isoform-specific binding mechanisms of
      phosphoinositide 3-kinase inhibitors.
AB  - Phosphoinositide 3-kinase (PI3K) is known to be closely related to tumorigenesis
      and cell proliferation, and controls a variety of cellular processes, including
      proliferation, growth, apoptosis, migration, metabolism, etc. The PI3K family
      comprises eight catalytic isoforms, which are subdivided into three classes.
      Recently, the discovery of inhibitors that block a single isoform of PI3K has
      continued to attract special attention because they may have higher selectivity
      for certain tumors and less toxicity for healthy cells. The PI3Kbeta and
      PI3Kdelta share fewer studies than alpha/gamma, and therefore, in this work, the
      combination of molecular dynamics simulations and free energy calculations was
      employed to explore the binding of three isoform-specific PI3K inhibitors (COM8,
      IC87114, and GDC-0941) to PI3Kbeta or PI3Kdelta. The isoform specificities of the
      studied inhibitors derived from the predicted binding free energies are in good
      agreement with the experimental data. In addition, the key residues critical for
      PI3Kbeta or PI3Kdelta selectivity were highlighted by decomposing the binding
      free energies into the contributions from individual residues. It was observed
      that although PI3Kbeta and PI3Kdelta share the conserved ATP-binding pockets,
      individual residues do behave differently, particularly the residues critical for
      PI3Kbeta or PI3Kdelta selectivity. It can be concluded that the inhibitor
      specificity between PI3Kbeta and PI3Kdelta is determined by the additive
      contributions from multiple residues, not just a single one. This study provides
      valuable information for understanding the isoform-specific binding mechanisms of
      PI3K inhibitors, and should be useful for the rational design of novel and
      selective PI3K inhibitors. 

PMID- 24336904
TI  - Effects of surface roughness of Ag thin films on surface-enhanced Raman
      spectroscopy of graphene: spatial nonlocality and physisorption strain.
AB  - Metallic nanostructures are widely used for surface-enhanced Raman spectroscopy
      (SERS). Nanoscale surface corrugation significantly affects the localized plasmon
      response and the subsequent Raman intensity of the molecules in close proximity
      to the nanostructures. Experimentally, the surface roughness of metal films can
      be controlled by adjusting the deposition conditions, and the resulting localized
      near-field properties can be probed by measuring the Raman spectrum of the
      conformally coated monolayer graphene. The well-known Raman characteristics of
      graphene and its atomic-level 2D nature make it an ideal test-bed for SERS
      measurements on corrugated metal films. In this work, we experimentally and
      theoretically study the effects of surface roughness of Ag thin films on the SERS
      of graphene. We find that the nonlocality effect of the metal dielectric response
      has to be taken into account for more accurate prediction of the SERS enhancement
      at large surface roughness. Our results also reveal that the effect of
      physisorption strain should be included to understand the Raman peak shift and
      spectral broadening. These observations are fundamentally important for
      understanding the SERS from metallic nanostructures with sub-nanoscale
      corrugation. 

PMID- 24336905
TI  - Oxacalix[4]arene-supported di-, tetra- and undecanuclear copper(II) clusters.
AB  - Oxacalix[4]arenes containing either one or two oxa-bridges afford di and
      undecanuclear Cu(II) clusters respectively upon reaction with cupric nitrate
      under facile conditions. Variation in reaction conditions results in formation of
      a tetranuclear Cu(II) cluster with mono-oxacalix[4]arene, representing a
      structural expansion of the dinuclear assembly. 

PMID- 24336906
TI  - Regioselective prenylation of bromocarbazoles by palladium(0)-catalysed cross
      coupling--synthesis of O-methylsiamenol, O-methylmicromeline and carquinostatin
      A.
AB  - We describe the regioselective prenylation of 3-bromocarbazole by palladium(0)
      catalysed cross coupling with a prenylstannane or a prenylboronate. The procedure
      is applied to the synthesis of precursors for biologically active carbazole
      alkaloids. 

PMID- 24336907
TI  - Effectiveness of nonpublic report cards for reducing trauma mortality.
AB  - IMPORTANCE: An Institute of Medicine report on patient safety that cited medical
      errors as the 8th leading cause of death fueled demand to use quality measurement
      as a catalyst for improving health care quality. OBJECTIVE: To determine whether
      providing hospitals with benchmarking information on their risk-adjusted trauma
      mortality outcomes will decrease mortality in trauma patients. DESIGN, SETTING,
      AND PARTICIPANTS: Hospitals were provided confidential reports of their trauma
      risk-adjusted mortality rates using data from the National Trauma Data Bank.
      Regression discontinuity modeling was used to examine the impact of nonpublic
      reporting on in-hospital mortality in a cohort of 326206 trauma patients admitted
      to 44 hospitals, controlling for injury severity, patient case mix, hospital
      effects, and preexisting time trends. MAIN OUTCOMES AND MEASURES: In-hospital
      mortality rates. RESULTS Performance benchmarking was not significantly
      associated with lower in-hospital mortality (adjusted odds ratio [AOR], 0.89; 95%
      CI, 0.68-1.16; P=.39). Similar results were obtained in secondary analyses after
      stratifying patients by mechanism of trauma: blunt trauma (AOR, 0.91; 95% CI,
      0.69-1.20; P=.51) and penetrating trauma (AOR, 0.75; 95% CI, 0.44-1.28; P=.29).
      We also did not find a significant association between nonpublic reporting and in
      hospital mortality in either low-risk (AOR, 0.84; 95% CI, 0.57-1.25; P=.40) or
      high-risk (AOR, 0.88; 95% CI, 0.67-1.17; P=.38) patients. CONCLUSIONS AND
      RELEVANCE Nonpublic reporting of hospital risk-adjusted mortality rates does not
      lead to improved trauma mortality outcomes. The findings of this study may prove
      useful to the American College of Surgeons as it moves ahead to further develop
      and expand its national trauma benchmarking program.

PMID- 24336908
TI  - Solvothermally exfoliated fluorographene for high-performance lithium primary
      batteries.
AB  - High-quality fluorographene (FG) was prepared by solvothermal exfoliation of
      fluorinated graphite (F-graphite) through intercalation of acetonitrile and
      chloroform with low boiling points. High-yield production of FG was demonstrated
      by wrinkled few-layered structures with disordered edges and poor regularity
      along the stacking direction. X-ray photo electron spectroscopy (XPS) spectra
      indicated that the intercalation of chloroform led to the partial transformation
      from covalent C-F bonds to semi-ionic C-F bonds. A lithium primary battery (Li
      battery) using a FG cathode exhibited a remarkable discharge rate performance
      because of good Li(+) diffusion and charge mobility through nanosheets. FG
      nanosheets exfoliated using chloroform showed a high specific capacity of 520 mA
      h g(-1) and a voltage platform of 2.18 V at a current density of 1 C, accompanied
      by a maximum power density of 4038 W kg(-1) at 3 C, which is almost four times
      higher than that of F-graphite. The results indicate that the solvothermal
      exfoliation using a low-boiling-point solvent is a facile, efficient and high
      yield approach to prepare high-purity FG nanosheets for high-performance Li
      batteries. 

PMID- 24336909
TI  - Invasive Salmonella infections in areas of high and low malaria transmission
      intensity in Tanzania.
AB  - BACKGROUND:  The epidemiology of Salmonella Typhi and invasive nontyphoidal
      Salmonella (NTS) differs, and prevalence of these pathogens among children in sub
      Saharan Africa may vary in relation to malaria transmission intensity. METHODS: 
      We compared the prevalence of bacteremia among febrile pediatric inpatients aged
      2 months to 13 years recruited at sites of high and low malaria endemicity in
      Tanzania. Enrollment at Teule Hospital, the high malaria transmission site, was
      from June 2006 through May 2007, and at Kilimanjaro Christian Medical Centre
      (KCMC), the low malaria transmission site, from September 2007 through August
      2008. Automated blood culture, malaria microscopy with Giemsa-stained blood
      films, and human immunodeficiency virus testing were performed. RESULTS:  At
      Teule, 3639 children were enrolled compared to 467 at KCMC. Smear-positive
      malaria was detected in 2195 of 3639 (60.3%) children at Teule and 11 of 460
      (2.4%) at KCMC (P < .001). Bacteremia was present in 336 of 3639 (9.2%) children
      at Teule and 20 of 463 (4.3%) at KCMC (P < .001). NTS was isolated in 162 of 3639
      (4.5%) children at Teule and 1 of 463 (0.2%) at KCMC (P < .001). Salmonella Typhi
      was isolated from 11 (0.3%) children at Teule and 6 (1.3%) at KCMC (P = .008).
      With NTS excluded, the prevalence of bacteremia at Teule was 5.0% and at KCMC
      4.1% (P = .391). CONCLUSIONS:  Where malaria transmission was intense, invasive
      NTS was common and Salmonella Typhi was uncommon, whereas the inverse was
      observed at a low malaria transmission site. The relationship between these
      pathogens, the environment, and the host is a compelling area for further
      research.

PMID- 24336910
TI  - Understanding BCG is the key to improving it.

PMID- 24336911
TI  - Protection by BCG vaccine against tuberculosis: a systematic review of randomized
      controlled trials.
AB  - BACKGROUND: Randomized trials assessing BCG vaccine protection against
      tuberculosis have widely varying results, for reasons that are not well
      understood. METHODS: We examined associations of trial setting and design with
      BCG efficacy against pulmonary and miliary or meningeal tuberculosis by
      conducting a systematic review, meta-analyses, and meta-regression. RESULTS: We
      identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or
      meningeal tuberculosis. Univariable meta-regression indicated efficacy against
      pulmonary tuberculosis varied according to 3 characteristics. Protection appeared
      greatest in children stringently tuberculin tested, to try to exclude prior
      infection with Mycobacterium tuberculosis or sensitization to environmental
      mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or
      infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not
      stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently
      or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55
      1.22, respectively). Protection was higher in trials further from the equator
      where environmental mycobacteria are less and with lower risk of diagnostic
      detection bias. These associations were attenuated in a multivariable model, but
      each had an independent effect. There was no evidence that efficacy was
      associated with BCG strain. Protection against meningeal and miliary tuberculosis
      was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently
      tuberculin tested (RR, 0.08; 95% CI, .03-.25). CONCLUSIONS: Absence of prior M.
      tuberculosis infection or sensitization with environmental mycobacteria is
      associated with higher efficacy of BCG against pulmonary tuberculosis and
      possibly against miliary and meningeal tuberculosis. Evaluations of new
      tuberculosis vaccines should account for the possibility that prior infection may
      mask or block their effects.

PMID- 24336912
TI  - Out of Africa: links between invasive nontyphoidal Salmonella disease, typhoid
      fever, and malaria.

PMID- 24336913
TI  - Editorial commentary: Management of hepatitis C Virus in HIV-infected patients in
      the era of direct-acting antivirals.

PMID- 24336915
TI  - Reduction of interleukin 8 and platelet-derived growth factor levels by topical
      ketorolac, 0.45%, in patients with diabetic retinopathy.
AB  - IMPORTANCE: Inhibition of inflammatory cytokines may have therapeutic effects in
      diabetic retinopathy (DR). OBJECTIVE: To compare aqueous and vitreous levels of
      17 inflammatory cytokines in patients treated preoperatively with topical
      ketorolac tromethamine, 0.45%, or placebo before pars plana vitrectomy for
      complications related to proliferative DR (PDR). DESIGN, SETTING, AND
      PARTICIPANTS: A prospective, randomized, placebo-controlled, patient-masked
      interventional study performed in a university academic hospital included 20 eyes
      from 20 patients undergoing pars plana vitrectomy for complications of PDR.
      INTERVENTIONS: Eyes were randomized to ketorolac tromethamine, 0.45% (Acuvail),
      or placebo 4 times daily for 3 days before pars plana vitrectomy. Undiluted
      aqueous and vitreous samples were taken at the time of surgery and immediately
      frozen at -80 degrees C. MAIN OUTCOMES AND MEASURES: Aqueous and vitreous levels
      of prostaglandin E2 and 16 other inflammatory cytokines implicated in the
      pathogenesis of DR. RESULTS: Prostaglandin E2, platelet-derived growth factor
      (PDGF) AA, eotaxin, vascular endothelial growth factor, interferon gamma
      inducible protein of 10 kDa, monocyte chemoattractant protein 1, growth-related
      oncogene, interleukin 6, interleukin 8 (IL-8), and tumor necrosis factor were
      detectable in the aqueous and vitreous of at least half of the eyes, and these
      cytokines were analyzed further. Aqueous levels were lower in the ketorolac group
      for all cytokines detected, but only the difference in IL-8 was statistically
      significant (52% reduction; P = .04). Levels of IL-8 (41% reduction; P = .002)
      and PDGF-AA (21% reduction; P = .009) were significantly lower in the vitreous of
      patients treated with ketorolac. CONCLUSIONS AND RELEVANCE: Topical ketorolac
      tromethamine, 0.45%, significantly lowered aqueous IL-8 levels and vitreous IL-8
      and PDGF-AA levels in this series of eyes, suggesting that it may cause
      meaningful inhibition of inflammatory cytokines implicated in the pathogenesis of
      DR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01609881.

PMID- 24336916
TI  - Direct functionalization of unactivated C-H bonds catalyzed by group 3-5 metal
      alkyl complexes.
AB  - This perspective summarizes direct C-H bond functionalization reactions catalyzed
      by group 3-5 metal alkyl complexes. Metal-carbon bonds of group 3-5 metals have
      potentially high reactivity toward both C-H bond activation reactions through the
      intrinsic sigma-bond metathesis pathway and insertion of unsaturated organic
      molecules. Upon the combination of these two elemental steps, direct C-H bond
      functionalization reactions of (hetero)aromatic compounds, methane, alkylamines,
      and terminal alkynes, proceed through C(sp)-H, C(sp(2))-H, and C(sp(3))-H bond
      activation reactions. Here we review as catalysts for these transformations not
      only simple metallocene complexes but also non-metallocene complexes supported by
      a variety of ligands, which are often superior in terms of catalyst design and
      catalytic activity. 

PMID- 24336917
TI  - Vacuum nano-hole array embedded organic light emitting diodes.
AB  - We demonstrated a nano-hole array (NHA) embedded structure that was fabricated
      for organic light emitting diodes (OLEDs) using a robust reverse transfer
      process. The NHA structure is proposed in this study as a strategy for maximizing
      the diffraction strength of two dimensional photonic crystals (PCs) by
      engineering vacuum nano-holes inside a dielectric slab. The electroluminescence
      (EL) intensity of the OLED was improved by more than twice. Such an optical
      enhancement was evaluated by using the angular dependence of photoluminescence
      (PL). The FDTD simulation was carried out to optimize the NHA structure for
      extraction of the emission induced from both vertical and horizontal dipoles. We
      explored the effect of the NHA structure on the extraction improvement converted
      from waveguide mode by measuring EL intensities of the devices with a hemisphere
      lens. In addition, the transfer process employed in this study yielded extremely
      low surface roughness, and thus outstanding electrical characteristics. 

PMID- 24336914
TI  - Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected
      men.
AB  - BACKGROUND: There is an international epidemic of hepatitis C virus (HCV)
      infection among human immunodeficiency virus (HIV)-infected men who have sex with
      men. Sustained virologic response (SVR) rates with pegylated interferon and
      ribavirin treatment are higher in these men during acute HCV than during chronic
      HCV, but treatment is still lengthy and SVR rates are suboptimal. METHODS: We
      performed a pilot study of combination therapy with telaprevir, pegylated
      interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men.
      Men who were treated prior to the availability of, or ineligible for, telaprevir
      were the comparator group. The primary endpoint was SVR12, defined as an HCV
      viral load <5 IU/mL at least 12 weeks after completing treatment. RESULTS: In the
      telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the
      comparator group. Among men with SVR, median time to undetectable viral load was
      week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53%
      had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in
      the telaprevir group received <=12 weeks of treatment and there were no relapses
      after treatment. The overall safety profile was similar to that known for
      telaprevir-based regimens. CONCLUSIONS: Incorporating telaprevir into treatment
      of acute genotype 1 HCV in HIV-infected men halved the treatment duration and
      increased the SVR rate. Larger studies should be done to confirm these findings.
      Clinicians should be alert to detect acute HCV infection of HIV-infected men to
      take advantage of this effective therapy and decrease further transmission in
      this epidemic.

PMID- 24336918
TI  - Factor XIIa inhibition by Infestin-4: in vitro mode of action and in vivo
      antithrombotic benefit.
AB  - Coagulation factor XII (FXII) plays a central role in initiating the intrinsic
      cascade of blood coagulation. Purified recombinant Human Albumin-tagged Infestin
      4 (rHA-Infestin-4) is a recently described FXIIa inhibitor that displayed strong
      anticoagulant activity without compromising haemostasis in several animal models.
      We pursued detailed in vitro characterisation of rHA-Infestin-4 and demonstrated
      that it is a competitive inhibitor of FXIIa with slow on and off rate constants
      for binding (kon=5x105 M-1s-1, koff=6x10-4 s-1), it can block FXIIa activation of
      its physiological substrates (plasma prekallikrein and FXI), and it can inhibit
      ellagic acid-triggered thrombin generation in plasma. Potency and selectivity
      profiling in enzyme assays suggest that rHA-Infestin-4 is indeed highly potent on
      FXIIa (IC50=0.3 +/- 0.06, 1.5 +/- 0.06, 1.2 +/- 0.09 nM, for human, rat, and
      rabbit FXIIa, respectively) with at least >100-fold selectivity against factors
      IIa, Xa, IXa, XIa, VIIa, and plasma kallikrein in all three species. rHA-Infestin
      4 dose-dependently and markedly reduced clot weight in the arteriovenous shunt
      thrombosis model in rats and rabbits, accompanied with minimal increase in
      cuticle bleeding times in either species. rHA-Infestin-4 treatment at 5 mg/kg in
      rabbit resulted in a 13% reduction in ex vivo FXa activity, demonstrating a
      modest off-target effect. In summary, our findings confirmed and extended
      previous reports that inhibition of FXIIa by rHA-Infestin-4 can produce strong
      antithrombotic efficacy while preserving haemostasis. Our comprehensive
      selectivity profiling, mode of action, and kinetic studies of rHA-Infestin-4
      reveal limitations of this molecule and offer new perspectives on any potential
      effort of discovering novel FXIIa inhibitors. 

PMID- 24336919
TI  - A single-chain TALEN architecture for genome engineering.
AB  - Transcription-activator like effector nucleases (TALENs) are tailor-made DNA
      endonucleases and serve as a powerful tool for genome engineering. Site-specific
      DNA cleavage can be made by the dimerization of FokI nuclease domains at custom
      targeted genomic loci, where a pair of TALENs must be positioned in close
      proximity with an appropriate orientation. However, the simultaneous delivery and
      coordinated expression of two bulky TALEN monomers (>100 kDa) in cells may be
      problematic to implement for certain applications. Here, we report the
      development of a single-chain TALEN (scTALEN) architecture, in which two FokI
      nuclease domains are fused on a single polypeptide. The scTALEN was created by
      connecting two FokI nuclease domains with a 95 amino acid polypeptide linker,
      which was isolated from a linker library by high-throughput screening. We
      demonstrated that scTALENs were catalytically active as monomers in yeast and
      human cells. The use of this novel scTALEN architecture should reduce protein
      payload, simplify design and decrease production cost. 

PMID- 24336920
TI  - A highly porous three-dimensional aluminum phosphonate with hexagonal channels:
      synthesis, structure and adsorption properties.
AB  - A 3D porous aluminum(III) trisphosphonate, constructed from 1D inorganic aluminum
      phosphate chains and tripodal organic linkers, contains large hexagonal channels
      (1.24 nm in diameter) and a highly accessible void (50.3%) which allow it to have
      a fast and relatively high uptake of H2, N2 and CO2.

PMID- 24336921
TI  - Impaired glucose tolerance in low-carbohydrate diet: maybe only a physiological
      state.

PMID- 24336922
TI  - Neanderthal introgression at chromosome 3p21.31 was under positive natural
      selection in East Asians.
AB  - Studies of the Neanderthal and Denisovan genomes demonstrate archaic hominin
      introgression in Eurasians. Here, we present evidence of Neanderthal
      introgression within the chromosome 3p21.31 region, occurring with a high
      frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in
      Europeans. We also detected a signal of strong positive selection in this region
      only in East Asians. Our data indicate that likely candidate targets of selection
      include rs12488302-T and its associated alleles--among which four are
      nonsynonymous, including rs35455589-G in HYAL2, a gene related to the cellular
      response to ultraviolet-B irradiation. Furthermore, suggestive evidence supports
      latitude-dependent selection, implicating a role of ultraviolet-B. Interestingly,
      the distribution of rs35455589-G suggests that this allele was lost during the
      exodus of ancestors of modern Eurasians from Africa and reintroduced to Eurasians
      from Neanderthals.

PMID- 24336923
TI  - Cytonuclear interactions and relaxed selection accelerate sequence evolution in
      organelle ribosomes.
AB  - Many mitochondrial and plastid protein complexes contain subunits that are
      encoded in different genomes. In animals, nuclear-encoded mitochondrial proteins
      often exhibit rapid sequence evolution, which has been hypothesized to result
      from selection for mutations that compensate for changes in interacting subunits
      encoded in mutation-prone animal mitochondrial DNA. To test this hypothesis, we
      analyzed nuclear genes encoding cytosolic and organelle ribosomal proteins in
      flowering plants. The model angiosperm genus Arabidopsis exhibits low organelle
      mutation rates, typical of most plants. Nevertheless, we found that (nuclear
      encoded) subunits of organelle ribosomes in Arabidopsis have higher amino acid
      sequence polymorphism and divergence than their counterparts in cytosolic
      ribosomes, suggesting that organelle ribosomes experience relaxed functional
      constraint. However, the observed difference between organelle and cytosolic
      ribosomes was smaller than in animals and could be partially attributed to rapid
      evolution in N-terminal organelle-targeting peptides that are not involved in
      ribosome function. To test the role of organelle mutation more directly, we used
      transcriptomic data from an angiosperm genus (Silene) with highly variable rates
      of organelle genome evolution. We found that Silene species with unusually fast
      evolving mitochondrial and plastid DNA exhibited increased amino acid sequence
      divergence in ribosomal proteins targeted to the organelles but not in those that
      function in cytosolic ribosomes. Overall, these findings support the hypothesis
      that rapid organelle genome evolution has selected for compensatory mutations in
      nuclear-encoded proteins. We conclude that coevolution between interacting
      subunits encoded in different genomic compartments within the eukaryotic cell is
      an important determinant of variation in rates of protein sequence evolution. 

PMID- 24336924
TI  - Meiosis gene inventory of four ciliates reveals the prevalence of a synaptonemal
      complex-independent crossover pathway.
AB  - To establish which meiosis genes are present in ciliates, and to look for clues
      as to which recombination pathways may be treaded by them, four genomes were
      inventoried for 11 meiosis-specific and 40 meiosis-related genes. We found that
      the set of meiosis genes shared by Tetrahymena thermophila, Paramecium
      tetraurelia, Ichthyophthirius multifiliis, and Oxytricha trifallax is consistent
      with the prevalence of a Mus81-dependent class II crossover pathway that is
      considered secondary in most model eukaryotes. There is little evidence for a
      canonical class I crossover pathway that requires the formation of a synaptonemal
      complex (SC). This gene inventory suggests that meiotic processes in ciliates
      largely depend on mitotic repair proteins for executing meiotic recombination. We
      propose that class I crossovers and SCs were reduced sometime during the
      evolution of ciliates. Consistent with this reduction, we provide microscopic
      evidence for the presence only of degenerate SCs in Stylonychia mytilus. In
      addition, lower nonsynonymous to synonymous mutation rates of some of the meiosis
      genes suggest that, in contrast to most other nuclear genes analyzed so far,
      meiosis genes in ciliates are largely evolving at a slower rate than those genes
      in fungi and animals. 

PMID- 24336925
TI  - Inheritance and mapping of Mj-2, a new source of root-knot nematode (Meloidogyne
      javanica) resistance in carrot.
AB  - Root-knot nematodes limit carrot production around the world by inducing taproot
      forking and galling deformities that render carrots unmarketable. In warmer
      climates, Meloidogyne javanica and Meloidogyne incognita are most prevalent. In
      F2 and F3 progeny from the cross between an Asian carrot resistant to M.
      javanica, PI 652188, and a susceptible carrot, resistance response was
      incompletely dominant with a relatively high heritability (H (2) = 0.78) and
      provided evidence for a single gene, designated Mj-2, contributing to resistance.
      Molecular markers linked to the previously described root-knot nematode
      resistance gene, Mj-1 on chromosome 8 derived from "Brasilia," demonstrated that
      Mj-2 does not map to that same locus but is on the same chromosome. 

PMID- 24336926
TI  - Resequencing data indicate a modest effect of domestication on diversity in
      barley: a cultigen with multiple origins.
AB  - The levels of diversity and extent of linkage disequilibrium in cultivated
      species are largely determined by diversity in their wild progenitors. We report
      a comparison of nucleotide sequence diversity in wild and cultivated barley
      (Hordeum vulgare ssp. spontaneum and ssp. vulgare) at 7 nuclear loci totaling
      9296bp, using sequence from Hordeum bulbosum to infer the ancestral state of
      mutations. The sample includes 36 accessions of cultivated barley, including 23
      landraces (cultivated forms not subject to modern breeding) and 13 cultivated
      lines and genetic stocks compared to either 25 or 45 accessions of wild barley
      for the same loci. Estimates of nucleotide sequence diversity indicate that
      landraces retain >80% of the diversity in wild barley. The primary population
      structure in wild barley, which divides the species into eastern and western
      populations, is reflected in significant differentiation at all loci in wild
      accessions and at 3 of 7 loci in landraces. "Oriental" landraces have slightly
      higher diversity than "Occidental" landraces. Genetic assignment suggests more
      admixture from Occidental landraces into Oriental landraces than the converse,
      which may explain this difference. Based on thetapi for silent sites, modern
      western cultivars have ~73% of the diversity found in landraces and ~71% of the
      diversity in wild barley. 

PMID- 24336927
TI  - Mapping genes to chicken microchromosome 16 and discovery of olfactory and
      scavenger receptor genes near the major histocompatibility complex.
AB  - Trisomy mapping is a powerful method for assigning genes to chicken
      microchromosome 16 (GGA 16). The single chicken nucleolar organizer region (NOR),
      the 2 major histocompatibility complex regions (MHC-Y and MHC-B), and CD1 genes
      were all previously assigned to GGA 16 using trisomy mapping. Here, we combined
      array comparative genomic hybridization with trisomy mapping to screen unassigned
      genomic scaffolds (consigned temporarily to chrUn_random) for sequences
      originating from GGA 16. A number of scaffolds mapped to GGA 16. Among these were
      scaffolds that contain genes for olfactory (OR) and cysteine-rich domain
      scavenger (SRCR) receptors, along with a number of genes that encode putative
      immunoglobulin-like receptors and other molecules. We used high-resolution
      cytogenomic analyses to confirm assignment of OR and SRCR genes to GGA 16 and to
      pinpoint members of these gene families to the q-arm in partially overlapping
      regions between the centromere and the NOR. Southern blots revealed sequence
      polymorphism within the OR/SRCR region and linkage with the MHC-Y region, thereby
      providing evidence for conserved linkage between OR genes and the MHC within
      birds. This work localizes OR genes to the vicinity of the chicken MHC and
      assigns additional genes, including immune defense genes, to GGA 16. 

PMID- 24336928
TI  - A call for tiger management using "reserves" of genetic diversity.
AB  - Tigers (Panthera tigris), like many large carnivores, are threatened by
      anthropogenic impacts, primarily habitat loss and poaching. Current conservation
      plans for tigers focus on population expansion, with the goal of doubling census
      size in the next 10 years. Previous studies have shown that because the
      demographic decline was recent, tiger populations still retain a large amount of
      genetic diversity. Although maintaining this diversity is extremely important to
      avoid deleterious effects of inbreeding, management plans have yet to consider
      predictive genetic models. We used coalescent simulations based on previously
      sequenced mitochondrial fragments (n = 125) from 5 of 6 extant subspecies to
      predict the population growth needed to maintain current genetic diversity over
      the next 150 years. We found that the level of gene flow between populations has
      a large effect on the local population growth necessary to maintain genetic
      diversity, without which tigers may face decreases in fitness. In the absence of
      gene flow, we demonstrate that maintaining genetic diversity is impossible based
      on known demographic parameters for the species. Thus, managing for the genetic
      diversity of the species should be prioritized over the riskier preservation of
      distinct subspecies. These predictive simulations provide unique management
      insights, hitherto not possible using existing analytical methods.

PMID- 24336929
TI  - Mapping of seed shattering loci provides insights into origin of weedy rice and
      rice domestication.
AB  - Seed shattering is an important trait that distinguishes crop cultivars from the
      wild and weedy species. The genetics of seed shattering was investigated in this
      study to provide insights into rice domestication and the evolution of weedy
      rice. Quantitative trait locus (QTL) analysis, conducted in 2 recombinant inbred
      populations involving 2 rice cultivars and a weedy rice accession of the southern
      United States, revealed 3-5 QTLs that controlled seed shattering with 38-45% of
      the total phenotypic variation. Two QTLs on chromosomes 4 and 10 were consistent
      in both populations. Both cultivar and weedy rice contributed alleles for
      increased seed shattering. Genetic backgrounds affected both QTL number and the
      magnitude of QTL effects. The major QTL qSH4 and a minor QTL qSH3 were validated
      in near-isogenic lines, with the former conferring a significantly higher degree
      of seed shattering than the latter. Although the major QTL qSH4 overlapped with
      the sh4, the presence of the nonshattering single nucleotide polymorphism allele
      in the weedy rice accession suggested involvement of a linked locus or an
      alternative molecular genetic mechanism. Overlapping of several QTLs with those
      from earlier studies indicated that weedy rice may have been derived from the
      wild species Oryza rufipogon. Natural hybridization of rice cultivars with the
      highly variable O. rufipogon present in different geographic regions might be
      responsible for the evolution of a wide range of phenotypic and genotypic
      variabilities seen in weedy rice populations worldwide. 

PMID- 24336931
TI  - Laser treatment of traumatic scars with an emphasis on ablative fractional laser
      resurfacing: consensus report.
AB  - IMPORTANCE: Despite expert wound care and assiduous management with traditional
      therapy, poor cosmetic outcomes, restricted motion, and symptoms such as pain and
      itch are a pervasive problem of disfiguring and debilitating scars. The advent of
      ablative fractional photothermolysis within the past decade and its application
      to the treatment of traumatic scars represents a breakthrough in the restoration
      of function and cosmetic appearance for injured patients, but the procedure is
      not widely used. OBJECTIVE: To provide a synthesis of our current clinical
      experience and available literature regarding the laser treatment of traumatic
      scars with an emphasis on fractional resurfacing. EVIDENCE REVIEW: Eight
      independent, self-selected academic and military dermatology and plastic surgery
      physicians with extensive experience in the use of lasers for scar treatment
      assembled for a 2-day ad hoc meeting on January 19 and 20, 2012. Consensus was
      based largely on expert opinion, but relevant literature was cited where it
      exists. FINDINGS: After consensus was appraised, we drafted the manuscript in
      sections during the course of several months. The draft was then circulated among
      all panel members for final review and comment. Our consensus is that laser
      treatment, particularly ablative fractional resurfacing, deserves a prominent
      role in future scar treatment paradigms, with the possible inclusion of early
      intervention for contracture avoidance and assistance with wound healing.
      CONCLUSIONS AND RELEVANCE: Laser scar therapy, particularly fractional ablative
      laser resurfacing, represents a promising and vastly underused tool in the
      multidisciplinary treatment of traumatic scars. Changes to existing scar
      treatment paradigms should include extensive integration of fractional
      resurfacing and other combination therapies guided by future research.

PMID- 24336932
TI  - Molecular dynamics approaches to the design and synthesis of PCB targeting
      molecularly imprinted polymers: interference to monomer-template interactions in
      imprinting of 1,2,3-trichlorobenzene.
AB  - The interactions between each component of the pre-polymerisation mixtures used
      in the synthesis of molecularly imprinted polymers (MIP) specific for 1,2,3,4,5
      pentachlorobenzene (1) and 1,2,3-trichlorobenzene (2) were examined in four
      molecular dynamics simulations. These simulations revealed that the relative
      frequency of functional monomer-template (FM-T) interactions was consistent with
      results obtained by the synthesis and evaluation of the actual MIPs. The higher
      frequency of 1 interaction with trimethylstyrene (TMS; 54.7%) than 1 interaction
      with pentafluorostyrene (PFS; 44.7%) correlated with a higher imprinting factor
      (IF) of 2.1 vs. 1.7 for each functional monomer respectively. The higher
      frequency of PFS interactions with 2 (29.6%) than TMS interactions with 2 (1.9%)
      also correlated well with the observed differences in IF (3.7) of 2 MIPs
      imprinted using PFS as the FM than the IF (2.8) of 2 MIPs imprinted using TMS as
      the FM. The TMS-1 interaction dominated the molecular simulation due to high
      interaction energies, but the weaker TMS-2 resulted in low interaction
      maintenance, and thus lower IF values. Examination of the other pre
      polymerisation mixture components revealed that the low levels of TMS-2
      interaction was, in part, due to interference caused by the cross linker (CL)
      ethyleneglycol dimethylacrylate (EGDMA) interactions with TMS. The main reason
      was, however, attributed to MeOH interactions with TMS in both a hydrogen bond
      and perpendicular configuration. This positioned a MeOH directly above the pi
      orbital of all TMS for an average of 63.8% of MD2 creating significant
      interference to pi-pi stacking interactions between 2 and TMS. These findings are
      consistent with the deviation from the 'normal' molecularly imprinted polymer
      synthesis ratio of 1 : 4 : 20 (T : FM : CL) of 20 : 1 : 29 and 15 : 6 : 29
      observed with 2 and TMS and PFS respectively. Our molecular dynamics simulations
      correctly predicted the high level of interference from other MIP synthesis
      components. The effect on PFS-1 interaction by MeOH was significantly lower and
      thus this system was not adversely affected. 

PMID- 24336933
TI  - Graft adhesion in descemet membrane endothelial keratoplasty dependent on size of
      removal of host's descemet membrane.
AB  - IMPORTANCE: It is essential to devise strategies that improve graft adhesion
      after Descemet membrane endothelial keratoplasty (DMEK) to reduce the rebubbling
      rate. OBJECTIVE: To evaluate the influence of the extent of descemetorhexis on
      graft adhesion properties after DMEK. DESIGN, SETTING, AND PARTICIPANTS: Single
      surgeon, retrospective, observational case series conducted in the Department of
      Ophthalmology, University of Erlangen-Nuremberg, Germany, that reviewed the
      medical records of 200 consecutive patients undergoing DMEK. Fifty-three eyes of
      51 patients undergoing DMEK for Fuchs endothelial dystrophy fulfilling the
      inclusion criteria were enrolled in this study. Based on intraoperative drawings,
      postoperative slitlamp examination, and photographs, eyes were divided into 2
      groups. The diameter of the descemetorhexis was approximately 10 mm in group A
      (30 eyes), resulting in a peripheral 1-mm zone of denuded stroma between the
      graft and the host's Descemet membrane, and approximately 6 mm in group B (23
      eyes), resulting in a peripheral 1-mm zone of overlapping between the graft and
      the host's Descemet membrane. MAIN OUTCOMES AND MEASURES: Graft detachment rate,
      extent of graft detachment (in clock hours of graft's circumference), and
      rebubbling rate. RESULTS: Four days after DMEK, the graft detachment rate was
      33.3% (10 of 30) in group A and 78.3% (18 of 23) in group B (P = .002). The mean
      (SD) extent of graft detachment was 0.6 (0.9) and 2.8 (2.5) clock hours in groups
      A and B, respectively (P < .001), 4 days after surgery. The rebubbling rate was
      6.7% (2 of 30) and 30.4% (7 of 23) for groups A and B, respectively (P = .03).
      CONCLUSIONS AND RELEVANCE: A larger descemetorhexis in DMEK is correlated with
      better graft adhesion and lower rebubbling rates. Therefore, patients with a
      larger descemetorhexis require less intensive follow-up.

PMID- 24336934
TI  - Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1
      induced by LPS in endothelial cells by inhibiting MAP kinase signaling.
AB  - The expression of adhesion molecules in endothelial cells elicited by
      lipopolysaccharide (LPS) is involved in the adhesive interaction between
      endothelial cells and monocytes in inflammation. In this study, in order to
      characterize the anti-inflammatory effects of chitosan oligosaccharides (COS) on
      LPS-induced inflammation and to elucidate the underlying mechanisms, the mRNA
      levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were measured
      in porcine iliac artery endothelial cells (PIECs). When these cells were treated
      with COS, the LPS-induced mRNA expression of E-selectin and ICAM-1 was reduced
      through the inhibition of the signal transduction cascade, p38 mitogen-activated
      protein kinase (MAPK)/extracellular regulated protein kinase 1/2 (ERK1/2) and
      nuclear factor-kappaB (NF-kappaB). Moreover, through the inhibition of p38 MAPK
      and ERK1/2, COS suppressed the LPS-induced NF-kappaB p65 translocation. We found
      that COS suppressed the phosphorylation of p38 MAPK and the translocation of NF
      kappaB p65 into the nucleus in a dose-dependent manner, and inhibited the
      adhesion of U973 cells to PIECs. Based on these results, it can be concluded that
      COS downregulate the expression of E-selectin and ICAM-1 by inhibiting the
      phosphorylation of MAPKs and the activation of NF-kappaB in LPS-treated PIECs.
      Our study demonstrates the valuable anti-inflammatory properties of COS.

PMID- 24336935
TI  - Surfactant behaviour of metallacarboranes. A study based on the electrolysis of
      water.
AB  - [3,3'-Co(1,2-C2B9H11)2](-), [1](-), and its chloroderivatives have been described
      as displaying surfactant/aggregation properties. We have studied their behaviour
      as electrolytes in the water electrolysis process. The electrolysis experiments
      support the surfactant behaviour of these compounds. These conclusions have been
      drawn on the grounds of the intensity/voltage (I/V) curves of water splitting
      into H2 and O2 of aqueous solutions in which the electrolytes have been tested at
      the same concentration. The I/V curves have permitted us to map and group the
      different electrolytes studied in this work. Three differentiated zones have been
      observed: one for true electrolytes, NO3(-) and ClO4(-); a second one for
      intermediate electrolytes, BF4(-) and p-toluenesulfonate (PTS); and a third
      having the surfactant dodecylbenzenesulfonate (DBS), [1](-) and its
      chloroderivatives. The incorporation into the study of the chloroderivatives of
      [1](-) has allowed us to correlate molecular structure features with aqueous
      performance. The studied chloroderivatives perform better as electrolytes in
      accordance with the descending order of available B-H groups. This comes from the
      higher capacity to generate B-H...H-C(c) dihydrogen bonds in the non- or less
      halogenated molecules, considered one of the main reasons for the generation of
      the aggregates. In order to generate B-H...H-C(c) dihydrogen bonds the H-C(c)
      from the carborane cluster is needed. [B12H12](2-) was chosen to prove the
      hypothesis as it has B-H units but lacks H-C(c) units. Consequently, it should
      not produce self-assembling motifs, as is the case. [B12H12](2-) has an aqueous
      behaviour similar to SO4(2-).

PMID- 24336936
TI  - Insights into the role of the beta-2 microglobulin D-strand in amyloid propensity
      revealed by mass spectrometry.
AB  - In vivo beta-2 microglobulin (beta2m) forms amyloid fibrils that are associated
      with the disease dialysis-related amyloidosis. Here, electrospray ionisation-ion
      mobility spectrometry-mass spectrometry has been used to compare the oligomers
      formed from wild-type beta2m with those formed from a variant of the protein
      containing a single point mutation in the D strand, H51A, during in vitro fibril
      assembly. Using the amyloid-binding fluorescent dye, Thioflavin T, to monitor
      fibrillation kinetics, H51A was shown to exhibit a two-fold increase in the lag
      time of fibril formation. Despite this, comparison of the oligomeric species
      observed during the lag-time of self-aggregation indicated that H51A had a higher
      population of oligomers, and formed oligomers of higher order, than wild-type
      beta2m. The cross-sectional areas of the oligomers arising from H51A and wild
      type protein were indistinguishable, although the H51A oligomers were shown to
      have a significantly higher kinetic stability on account of their reluctance to
      undergo sub-unit exchange when mixed with 15N-labelled protein. Together the data
      reveal a significant effect of His51, and thus that of the D-strand sequence, on
      amyloid formation. The results also highlight the power of mass spectrometry in
      probing complex biochemical mechanisms in real-time. 

PMID- 24336937
TI  - Two small (p)ppGpp synthases in Staphylococcus aureus mediate tolerance against
      cell envelope stress conditions.
AB  - The stringent response is a conserved global regulatory mechanism that is related
      to the synthesis of (p)ppGpp nucleotides. Gram-positive bacteria, such as
      Staphylococcus aureus, possess three (p)ppGpp synthases: the bifunctional RSH
      (RelA/SpoT homolog) protein, which consists of a (p)ppGpp synthase and a (p)ppGpp
      hydrolase domain, and two truncated (p)ppGpp synthases, designated RelP and RelQ.
      Here, we characterized these two small (p)ppGpp synthases. Biochemical analyses
      of purified proteins and in vivo studies revealed a stronger synthetic activity
      for RelP than for RelQ. However, both enzymes prefer GDP over GTP as the
      pyrophosphate recipient to synthesize ppGpp. Each of the enzymes was shown to be
      responsible for the essentiality of the (p)ppGpp hydrolase domain of the RSH
      protein. The staphylococcal RSH-hydrolase is an efficient enzyme that prevents
      the toxic accumulation of (p)ppGpp. Expression of (p)ppGpp synthases in a
      hydrolase-negative background leads not only to growth arrest but also to cell
      death. Transcriptional analyses showed that relP and relQ are strongly induced
      upon vancomycin and ampicillin treatments. Accordingly, mutants lacking relP and
      relQ showed a significantly reduced survival rate upon treatments with cell wall
      active antibiotics. Thus, RelP and RelQ are active (p)ppGpp synthases in S.
      aureus that are induced under cell envelope stress to mediate tolerance against
      these conditions. 

PMID- 24336938
TI  - the Eutt enzyme of Salmonella enterica is a unique ATP:Cob(I)alamin
      adenosyltransferase metalloprotein that requires ferrous ions for maximal
      activity.
AB  - ATP:co(I)rrinoid adenosyltransferase (ACAT) enzymes convert vitamin B12 to
      coenzyme B12. EutT is the least understood ACAT. We report the purification of
      EutT to homogeneity and show that, in vitro, free dihydroflavins drive the
      adenosylation of cob(II)alamin bound to EutT. Results of chromatography analyses
      indicate that EutT is dimeric in solution, and unlike other ACATs, EutT catalyzes
      the reaction with sigmoidal kinetics indicative of positive cooperativity for
      cob(II)alamin. Maximal EutT activity was obtained after metalation with ferrous
      ions. EutT/Fe(II) protein lost all activity upon exposure to air and H2O2,
      consistent with previously reported results indicating that EutT was an oxygen
      labile metalloprotein containing a redox-active metal. Results of in vivo and in
      vitro analyses of single-amino-acid variants affecting a HX11CCXXC(83) motif
      conserved in EutT proteins showed that residues His67, Cys80, and Cys83 were
      required for EutT function in vivo, while Cys79 was not. Unlike that of other
      variants, the activity of the EutT(C80A) variant was undetectable in vitro,
      suggesting that Cys80 was critical to EutT function. Results of circular
      dichroism studies indicate that the presence or absence of a metal ion does not
      affect protein folding. EutT can now be purified in the presence of oxygen and
      reactivated with ferrous ions for maximal activity. 

PMID- 24336939
TI  - Comparative phylogenomics and evolution of the Brucellae reveal a path to
      virulence.
AB  - Brucella species include important zoonotic pathogens that have a substantial
      impact on both agriculture and human health throughout the world. Brucellae are
      thought of as "stealth pathogens" that escape recognition by the host innate
      immune response, modulate the acquired immune response, and evade intracellular
      destruction. We analyzed the genome sequences of members of the family
      Brucellaceae to assess its evolutionary history from likely free-living soil
      based progenitors into highly successful intracellular pathogens. Phylogenetic
      analysis split the genus into two groups: recently identified and early-dividing
      "atypical" strains and a highly conserved "classical" core clade containing the
      major pathogenic species. Lateral gene transfer events brought unique genomic
      regions into Brucella that differentiated them from Ochrobactrum and allowed the
      stepwise acquisition of virulence factors that include a type IV secretion
      system, a perosamine-based O antigen, and systems for sequestering metal ions
      that are absent in progenitors. Subsequent radiation within the core Brucella
      resulted in lineages that appear to have evolved within their preferred mammalian
      hosts, restricting their virulence to become stealth pathogens capable of causing
      long-term chronic infections. 

PMID- 24336940
TI  - Type 1 fimbriae contribute to catheter-associated urinary tract infections caused
      by Escherichia coli.
AB  - Biofilm formation on catheters is thought to contribute to persistence of
      catheter-associated urinary tract infections (CAUTI), which represent the most
      frequent nosocomial infections. Knowledge of genetic factors for catheter
      colonization is limited, since their role has not been assessed using
      physicochemical conditions prevailing in a catheterized human bladder. The
      current study aimed to combine data from a dynamic catheterized bladder model in
      vitro with in vivo expression analysis for understanding molecular factors
      relevant for CAUTI caused by Escherichia coli. By application of the in vitro
      model that mirrors the physicochemical environment during human infection, we
      found that an E. coli K-12 mutant defective in type 1 fimbriae, but not isogenic
      mutants lacking flagella or antigen 43, was outcompeted by the wild-type strain
      during prolonged catheter colonization. The importance of type 1 fimbriae for
      catheter colonization was verified using a fimA mutant of uropathogenic E. coli
      strain CFT073 with human and artificial urine. Orientation of the invertible
      element (IE) controlling type 1 fimbrial expression in bacterial populations
      harvested from the colonized catheterized bladder in vitro suggested that the
      vast majority of catheter-colonizing cells (up to 88%) express type 1 fimbriae.
      Analysis of IE orientation in E. coli populations harvested from patient
      catheters revealed that a median level of ~73% of cells from nine samples have
      switched on type 1 fimbrial expression. This study supports the utility of the
      dynamic catheterized bladder model for analyzing catheter colonization factors
      and highlights a role for type 1 fimbriae during CAUTI. 

PMID- 24336941
TI  - Functional genetic analysis of the GarML gene cluster in Lactococcus garvieae
      DCC43 gives new insights into circular bacteriocin biosynthesis.
AB  - Garvicin ML (GarML) is a circular bacteriocin produced by Lactococcus garvieae
      DCC43. The recently published draft genome of this strain allowed determination
      of the genetic background for bacteriocin production. Bioinformatic analysis
      identified a gene cluster consisting of nine open reading frames likely involved
      in the production of and immunity to GarML. The garA gene encodes the bacteriocin
      precursor, garX a large transmembrane protein, garBCDE a putative immunity
      protein (garB) followed by an ATPase and two transmembrane proteins, and garFGH a
      putative ABC transporter complex. Functional genetic analysis revealed that
      deletion of garFGH had no effect on sensitivity to or production of GarML. In
      contrast, deletion of garBCDE or inactivation of garX resulted in high-level
      sensitivity to GarML and completely abolished production of active bacteriocin.
      Mass spectrometry of culture supernatants revealed that wild-type cultures
      contained the mature circular form as well as the linear forms of the
      bacteriocin, both with and without the three-amino-acid leader sequence, while
      bacteriocin-negative mutants contained only the linear forms. These results
      indicate that cleavage of the leader peptide precedes circularization and is
      likely performed by a functional entity separate from the GarML gene cluster. To
      our knowledge, this is the first conclusive evidence for these processes being
      separated in time. Loss of immunity and antimicrobial activity in addition to our
      inability to detect the circular bacteriocin in the DeltagarBCDE and garX::pCG47
      mutants demonstrate that both these units are indispensable for GarML
      biosynthesis as well as immunity. Furthermore, the results indicate that these
      genes are implicated in the circularization of the bacteriocin and that their
      functions are probably interlinked. 

PMID- 24336942
TI  - Targeting factor Xa and thrombin: impact on coagulation and beyond.
AB  - Great advances have been made in recent years in understanding the haemostatic
      system and the molecular and cellular basis of thrombus formation. Although
      directly targeting factor Xa or thrombin (factor IIa) for effective
      anticoagulation is now well established, evidence has emerged suggesting that
      factor Xa and thrombin are involved in other physiological and pathophysiological
      cellular processes, including inflammation. These non-haemostatic activities of
      factor Xa and thrombin are predominantly mediated via the activation of
      proteinase-activated receptors. Studies have indicated a potential role of
      coagulation proteins (including factor Xa and thrombin) in the progression of
      disease conditions such as atherothrombosis. Preclinical studies have provided
      evidence for the effects of direct factor Xa or direct thrombin inhibition beyond
      anticoagulation, including anti-inflammatory activities and atherosclerotic
      plaque stabilisation. In this article, the non-haemostatic activities of factor
      Xa and thrombin and the effects of direct inhibition of these coagulation factors
      on these activities are summarised. In addition, the potential roles of factor Xa
      and thrombin in atherosclerosis and atherothrombosis are explored and the
      cardiovascular profiles of rivaroxaban, apixaban and dabigatran etexilate
      observed in phase III clinical studies are discussed. 

PMID- 24336943
TI  - A multicenter clinicomycological study evaluating the spectrum of adult tinea
      capitis in Egypt.
AB  - INTRODUCTION: Tinea capitis (TC) is a common fungal infection in children but is
      less frequently encountered in adults. This study evaluates the clinical
      characteristics and mycological studies of adult TC among the Egyptian
      population. METHODS: A multicenter study included patients diagnosed with TC from
      2002 to 2012. RESULTS: The study included 58 patients with a predominance of
      females (84.5%). The average age was 43.2 years and the mean duration of lesions
      was 7.1 +/- 2.41 months. A history of close contact with animals was reported in
      17.2% and Hepatitis C virus infection was recorded in 34.4%. Clinically, scaly
      scalp (37.9%), alopecia (22.4%), and pyoderma-like lesions (13.8%) were the most
      common presentations. The parietal (27.6%) and temporal (25.8%) regions were the
      most affected areas. KOH mounting showed endothrix spores in 56.9%, ectothrix
      spores in 34.5%, and favic chaplets (hyphae) in 8.6%. Fungal culture showed
      Trichophyton violaceum in 56.9%, Microsporum audouinii in 19%, Microsporum canis
      in 15.5%, and Trichophyton schoenleini in 8.6%. CONCLUSIONS: Trichophyton
      violaceum is the most common cause of adult TC among Egyptians. Increased
      awareness of variable clinical forms of TC will help in identifying more cases,
      especially those with HCV infection and close contact with animals.

PMID- 24336944
TI  - Insulin-induced localized lipoatrophy.
AB  - Insulin lipoatrophy is a rare immunologic cutaneous complication in diabetes
      mellitus that presents with localized subcutaneous fat atrophy at the insulin
      injection site. We report the case of a 62-year-old woman with type 2 diabetes
      mellitus that developed localized lipoatrophy on the abdomen after 6 years of
      therapy with the insulin analogues detemir and aspart. 

PMID- 24336945
TI  - Figurate erythema in a patient with bullous pemphigoid and Toxocara infection.
AB  - Figurate erythema can appear in a wide spectrum of dermatological diseases.
      Rarely, it can present as an atypical manifestation of bullous pemphigoid. Among
      eosinophilic dermatoses, figurate erythema may appear in Wells syndrome, which
      has been occasionally reported in association with Toxocara infection. We present
      the case of an older female patient diagnosed with bullous pemphigoid, who
      presented with an unusual combination of blisters and figurate erythema outside
      the area of blister formation. In addition, high blood eosinophilia associated
      with lymph node and bone marrow eosinophilia was diagnosed and was causally
      related to Toxocara canis infection. The patient was treated with dapsone for
      bullous pemphigoid and with albendazole for toxocariosis, with complete
      regression of all skin lesions and blood eosinophilia. This paper discusses the
      possible etiopathogenesis of figurate erythema in our patient and summarizes
      previous clinical and histological findings in bullous pemphigoid and
      eosinophilic dermatoses presenting with figurate erythema lesions. 

PMID- 24336946
TI  - An alternative treatment for acroangiodermatitis: intermittent pneumatic
      compression therapy.

PMID- 24336947
TI  - Congenital temporal triangular alopecia: a typical Brauer nevus.

PMID- 24336948
TI  - Benefit of pacemaker therapy in patients with presumed neurally mediated syncope
      and documented asystole is greater when tilt test is negative: an analysis from
      the third International Study on Syncope of Uncertain Etiology (ISSUE-3).
AB  - BACKGROUND: In the Third International Study on Syncope of Uncertain Etiology
      (ISSUE-3), cardiac pacing was effective in reducing recurrence of syncope in
      patients with presumed neurally mediated syncope (NMS) and documented asystole
      but syncope still recurred in 25% of them at 2 years. We have investigated the
      role of tilt testing (TT) in predicting recurrences. METHODS AND RESULTS: In 136
      patients enrolled in the ISSUE-3, TT was positive in 76 and negative in 60. An
      asystolic response predicted a similar asystolic form during implantable loop
      recorder monitoring, with a positive predictive value of 86%. The corresponding
      values were 48% in patients with non-asystolic TT and 58% in patients with
      negative TT (P=0.001 versus asystolic TT). Fifty-two patients (26 TT+ and 26 TT-)
      with asystolic neurally mediated syncope received a pacemaker. Syncope recurred
      in 8 TT+ and in 1 TT- patients. At 21 months, the estimated product-limit syncope
      recurrence rates were 55% and 5%, respectively (P=0.004). The TT+ recurrence rate
      was similar to that seen in 45 untreated patients (control group), which was 64%
      (P=0.75). The recurrence rate was similar between 14 patients with asystolic and
      12 with non-asystolic responses during TT (P=0.53). CONCLUSIONS: Cardiac pacing
      was effective in neurally mediated syncope patients with documented asystolic
      episodes in whom TT was negative; conversely, there was insufficient evidence of
      efficacy from this data set in patients with a positive TT even when spontaneous
      asystole was documented. Present observations are unexpected and need to be
      confirmed by other studies. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01463358.

PMID- 24336949
TI  - Asparagine-linked glycosylation of bone morphogenetic protein-2 is required for
      secretion and osteoblast differentiation.
AB  - Bone morphogenetic protein-2 (BMP-2), a glycosylated protein, has been
      demonstrated to play a key role in osteoblast differentiation. However, the
      function of its glycosylation is incompletely understood. In this study, we
      examined the role that N-linked glycans (NLG) play in the secretion of BMP-2.
      Blocking the addition of NLGs or inhibiting initial glycan processing prevented
      the secretion of BMP-2. To identify the specific glycosylation sites, we
      abolished potential sites of N-linked glycosylation (Asn-Xaa-Ser/Thr) in BMP-2 by
      mutating the Asn residues to Gln individually or in combination, expressed the
      BMP-2 mutants in Chinese hamster ovary (CHO) and human embryonic kidney 293T
      (HEK293T) cells and determined their glycosylation state by using peptide:N
      glycosidase F and endoglycosidase H digestion. We found that human BMP-2 contains
      three NLG on N135, N200 and N338. Elimination of N-glycosylation by mutation of
      N135 (N135Q) abolished the BMP-2 secretion from CHO cells. Overexpression of the
      BMP-2 mutant N135Q elicited endoplasmic reticulum (ER) stress and retention
      within the ER in CHO cells, indicating that N-glycosylation is required for
      folding of human BMP-2. Furthermore, we demonstrated that glycosylation at N135
      was necessary for BMP-2-induced osteoblast differentiation in MC3T3-E1 cells.
      Taken together, these data provide further evidence of the critical role that
      individual NLG may play an important role in determining BMP-2 folding, secretion
      and function. 

PMID- 24336950
TI  - Metaphors, stigma and the 'Alzheimerization' of the euthanasia debate.
AB  - This paper reports the findings of an unobtrusive research inquiry investigating
      the possible use and misuse of Alzheimer's disease in public policy debate on the
      legalization of euthanasia. The component of the study being reported identified
      the problematic use of five key metaphors: the Alzheimer metaphor, which in turn
      was reinforced by three additional metaphors--the epidemic metaphor, the military
      metaphor, and the predatory thief metaphor; and the euthanasia metaphor. All
      metaphors were found to be morally loaded and used influentially to stigmatize
      Alzheimer's disease and mediate public opinion supporting the legalization of
      euthanasia as an end-of-life 'solution' for people with the disease. It is
      contended that, in the interests of promoting intellectual honesty and giving
      proper recognition to the extraordinary complexity of the issue, the problematic
      use and influence of metaphoric thinking in the public debate about Alzheimer's
      disease and euthanasia needs to be made transparent, questioned and challenged.

PMID- 24336951
TI  - The subjective experience of personhood in dementia care settings.
AB  - Within the social psychological understanding of dementia, individuals'
      personhood is central. A respect for personhood has been linked to successful
      person-centred care, yet research exploring subjective personhood in dementia is
      scarce. This study aimed to understand personhood by exploring the subjective
      experiences of those with dementia. Seven individuals with dementia were
      interviewed and interpretative phenomenological analysis was used to identify
      themes across accounts. Themes identified were: (1) working out the system and
      adapting in order to survive it--the 'peoplehood' of the system; (2) using past
      and future roles and experiences to manage the present--the transient nature of
      personhood; (3) being both an individual and a member of a group--the conflict of
      a dual role. The themes highlighted showed that individuals with dementia
      supported their personhood by drawing on their own, others' and the system's
      resources. The findings are discussed and links with existing literature and
      clinical implications are considered.

PMID- 24336952
TI  - Experiences of persons with early-onset dementia in everyday life: a qualitative
      study.
AB  - BACKGROUND: The small number of existing studies confirms that people with early
      onset dementia (EOD) need special assistance from the beginning and as the
      disease progresses. There is a need to develop services to respond to the
      specific needs of persons with EOD. AIM: To find out how people experience living
      with early-onset dementia, and to assess the implications for practice and the
      development of further services. METHOD: Grounded theory, a qualitative method,
      with interviews of 20 informants (aged 54-67 years; 12 of them men) during 2010
      2011. FINDINGS: One category, the process toward a dementia diagnosis, covered
      two subcategories; describing changes and being diagnosed. Another category
      fighting for dignity describes how the informants try to maintain their quality
      of life, covering two subcategories; intrapsychic challenges and social
      challenges. CONCLUSION: Health services should give persons with EOD the ability
      to maintain contact with society and their voices should not be overlooked.

PMID- 24336953
TI  - Contributions of an artistic educational program for older people with early
      dementia: an exploratory qualitative study.
AB  - OBJECTIVE: To describe a contemporary artistic educational program based on
      photographic cyanotype techniques and to present the results of the program
      carried out with older people with early dementia. We determined whether these
      people could participate in the program, their viewpoint about it, and what this
      program could contribute to their experience. METHOD: Twenty-one people diagnosed
      with mild or moderate dementia participated in a series of artistic education
      workshops. While conducting the workshops, participant observation was carried
      out, and the participants' engagement was assessed. Upon completing the series,
      five focus groups were held with the participants with dementia, and another
      focus group with their professional caretakers. RESULTS: We observed the
      participants' high level of commitment to the activity and their interest in
      learning new things. We also observed the participants' satisfaction during the
      creative process and with their results. The artistic activities not only
      reinforced the feelings of capacity of the participants with early dementia but
      also transmitted a positive image of them. CONCLUSIONS: Dementia was not an
      obstacle to participation in the program, which was an opportunity for
      creativity, learning, enjoyment, and communication for people with dementia. In
      the authors' opinion, facilitating access to art and artistic education to people
      with early dementia can contribute to enforcing their rights and to improving the
      care system.

PMID- 24336954
TI  - Doll therapy: a therapeutic means to meet past attachment needs and diminish
      behaviours of concern in a person living with dementia--a case study approach.
AB  - The aim of this research study was to examine the impact of the provision of a
      lifelike baby doll as a therapeutic tool on the behaviour of a person living with
      dementia. Specifically, this single case study assessed the potential benefits,
      if any, of the use of doll therapy in reducing behaviours of concern such as
      anxiety and agitation that may be associated with observed attachment needs of a
      person living with dementia. METHOD: A single case study of a female participant,
      with moderately advanced Alzheimer's disease, was the subject of this research.
      The case study used both qualitative and quantitative research design and
      methodology in data collection and analysis. RESULTS: Demonstrated that doll
      therapy was a positive intervention for the person living with dementia who was
      the participant in this research. The findings indicate a reduction in behaviours
      of concern related to the need for attachment and a considerable decline in
      levels of anxiety and agitation. There was extensive ongoing improvement in
      social interaction and communication. CONCLUSION: This research supports doll
      therapy as a therapeutic intervention that may be utilized within the ongoing
      care of some persons with dementia to meet needs for attachment and to reduce
      behaviours of concern. Despite some controversy on this topic, doll therapy
      should be considered as a therapeutic approach to further dementia care in light
      of this positive outcome.

PMID- 24336955
TI  - Inappropriate sexual behaviour and dementia: an exploration of staff experiences.
AB  - Research assessing the impact of inappropriate sexual behaviour (ISB) on staff
      working in dementia care is circumscribed, yet studies from comparable settings
      indicate that ISB appears uniquely challenging, particularly to personal and
      cultural values. This study explored staff experiences of ISB exhibited by older
      adults with a dementia. Fourteen staff working within an in-patient setting were
      interviewed. Participants' experiences of ISB appeared underpinned by complex
      social and psychological processes. Shock, embarrassment and incomprehension were
      prominent when ISB was initially encountered. Knowledge of dementia, familiarity
      with patients and social norms were important in contextualising ISB and staff
      often minimised its impact by construing a lack of capacity. Feelings about ISB
      appeared equivocal and findings suggest that the effect of ISB should be
      routinely considered in preparing staff who work within dementia care. 

PMID- 24336956
TI  - Perceived barriers to self-management for people with dementia in the early
      stages.
AB  - People with dementia in the early stages currently experience a care gap, which
      self-management may address. We explore perceived barriers to self-management.
      Using a systematic approach (logic mapping), 19 participants (people with
      dementia, carers, health care professionals and charity representatives)
      described self-management barriers facing people living with dementia. Thematic
      content analysis revealed six main themes: the lived experience of dementia,
      diagnosis, role of carer/family, impact of health care professionals,
      organisation of health services and societal views. People with dementia were
      seen as passive recipients of care, unable to self-manage owing to the impact of
      dementia on cognitive abilities. The need for interventions that are largely
      emotion focused, encourage activity maintenance and improve quality of life are
      described. Barriers to self-management exist at multiple levels, suggesting a
      whole-systems approach is required. 

PMID- 24336957
TI  - An evaluation of a therapeutic garden's influence on the quality of life of aged
      care residents with dementia.
AB  - To evaluate whether a therapeutic garden can improve the quality of life of aged
      care residents with dementia and their carers, objective instruments as well as
      interviews with residents, staff, and family members were employed. Residents'
      mean quality of life scores increased by just over 10%, mean depression scores
      decreased similarly and mean agitation scores decreased by almost half. Resident,
      staff and family member interviews elicited positive feedback including
      observations that it had improved the quality of life for residents and decreased
      staff and family stress levels. In sum, qualitative and quantitative pre and post
      findings indicate that an environmental change such as a therapeutic garden can
      improve the lives of aged care residents with dementia, and their formal and
      informal carers. 

PMID- 24336958
TI  - PP6C hotspot mutations in melanoma display sensitivity to Aurora kinase
      inhibition.
AB  - Recent whole genome melanoma sequencing studies have identified recurrent
      mutations in the gene encoding the catalytic subunit of serine/threonine
      phosphatase 6 (PPP6C/PP6C). However, the biochemical, functional, and clinical
      ramifications of these mutations are unknown. Sequencing PP6C from patients with
      melanoma (233 primary and 77 metastatic specimens) with extended prospective
      clinical outcome revealed a large number of hotspot mutations in patients with
      both primary and metastatic melanoma. Despite minimal association between stage
      and presence of PP6C mutations in patients with primary melanoma, a subpopulation
      of cells within each tumor did contain PP6C mutations, suggesting PP6C mutation
      is an early, but non-tumor-initiating event in melanoma. Among patients with
      primary melanoma with PP6C mutations, patients with stop mutations had
      significantly shorter recurrence-free survival compared with patients without
      stop mutations. In addition, PP6C mutations were independent of commonly observed
      BRAF and NRAS mutations. Biochemically, PP6C mutations could be classified as
      those that interact with PP6C regulatory subunits and those that do not.
      Mutations that did not bind to PP6C regulatory subunits were associated with
      increased phosphorylation of Aurora kinase, a PP6C substrate, and mitotic
      defects. However, both classes of PP6C mutations led to increased sensitivity to
      Aurora kinase inhibition. Together, these data support for the first time that
      PP6C mutations are molecularly, biochemically, and clinically heterogeneous.
      IMPLICATIONS: PP6C mutations have distinct functional and clinical consequences
      in melanoma, and confer sensitivity to Aurora A kinase inhibitors.

PMID- 24336959
TI  - Bismuth-based cyclic synthesis of 3,5-di-tert-butyl-4-hydroxybenzoic acid via the
      oxyarylcarboxy dianion, (O2CC6H2(t)Bu2O)2-.
AB  - 3,5-Di-tert-butyl-4-hydroxybenzoic acid can be made under mild conditions in a
      cyclic process from carbon dioxide and 3,5-di-tert-butyl-4-phenol using bismuth
      based C-H bond activation and CO2 insertion chemistry starting with the Bi(3+)
      complex, Ar'BiCl2, of the NCN pincer ligand, Ar' = 2,6-(Me2NCH2)2C6H3. Complexes
      of the recently discovered oxyaryl dianion, (C6H2(t)Bu2-3,5-O-4)(2-), and the
      oxyarylcarboxy dianion, [O2C(C6H2(t)Bu2-3,5-O-4)](2-), are intermediates in the
      process. Further studies of the oxyarylcarboxy dianion in Ar'Bi[O2C(C6H2(t)Bu2
      3,5-O-4)-kappa(2)O,O'], show that it undergoes decarboxylation upon reaction with
      I2 and it reacts with trimethylsilyl chloride to produce the trimethylsilyl ether
      of the trimethylsilyl ester of 3,5-di-tert-butyl-4-hydroxybenzoic acid and the
      Ar'BiCl2 starting material. 

PMID- 24336960
TI  - The long-term effects of splenectomy and subsequent interferon therapy in
      patients with HCV-related liver cirrhosis.
AB  - Partial splenic embolization (PSE) or splenectomy is widely performed to increase
      platelet counts for interferon (IFN) therapy. The aim of the present study was to
      evaluate the long-term effects of splenectomy and subsequent IFN therapy in
      patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). The present
      study included 19 patients with HCV-related LC who underwent splenectomy for
      thrombo-cytopenia caused by hypersplenism. IFN therapy was performed in all 19
      patients. The effects of splenectomy and subsequent IFN therapy on peripheral
      blood counts, liver function, carcinogenesis and survival rates were evaluated.
      Splenectomy was safely performed in all patients without major complications with
      the exception of portal thrombosis, which, however, it did not affect liver
      function when treated appropriately. Thrombocytopenia improved and IFN therapy
      could be performed in all the patients. A sustained virological response (SVR)
      was not observed in patients with genotype 1 although it was observed in 75% of
      patients with genotype 2. Due to severe side effects, five patients did not
      undergo scheduled IFN therapy. Over 5 years, the mean platelet number increased
      from 5.2 x 10(4) to 16.8 x 10(4)/mm3 (P<0.01) and liver function improved
      following splenectomy (albumin, Alb: 3.5-3.8 g/dl; total bilirubin, T-Bil: 1.0
      0.7 mg/dl; prothrombin time, PT: 74.1-97.7%; total cholesterol; T-cho: 140-168
      mg/dl; P<0.05). Hepatocellular carcinoma (HCC) occurred in only one patient
      during long-term observation and follow-up of the patients not presenting with
      HCC at entry. The results of the present study demonstrate that splenectomy
      followed by interferon therapy could be beneficial in patients with HCV-related
      LC.

PMID- 24336962
TI  - Ion-exchange synthesis of Ag/Ag2S/Ag3CuS2 ternary hollow microspheres with
      efficient visible-light photocatalytic activity.
AB  - Ternary Ag/Ag2S/Ag3CuS2 hollow microspheres were synthesized via an in situ ion
      exchange method using Cu7S4 hollow submicrospheres as the template. The as
      obtained Ag/Ag2S/Ag3CuS2 composite exhibited a well-defined uniform hollow
      microsphere morphology with an average diameter of about 1.3 MUm. The
      photocatalytic property of the as-prepared Ag/Ag2S/Ag3CuS2 hollow microsphere
      composite was investigated by the decomposition of methyl orange (MO) under
      visible light irradiation (lambda > 420 nm). It was shown that the photocatalytic
      activity of the Ag/Ag2S/Ag3CuS2 hollow microsphere was higher than those of
      Ag/Ag2S, Cu2O, Cu7S4 and P25 for the photodegradation of MO under visible light
      irradiation. Radical scavenger experiments demonstrated that superoxide radicals
      and holes were the main reactive species for MO degradation. 

PMID- 24336964
TI  - Teaching cosmetic dermatology without sacrificing the proper emphasis on medical
      dermatology.

PMID- 24336963
TI  - In silico profiling and structural insights of missense mutations in RET protein
      kinase domain by molecular dynamics and docking approach.
AB  - A major challenge remaining in drug design efforts towards protein kinase is due
      to the development of drug resistance initiated by the missense mutations in the
      kinase catalytic domain. Gain or loss of function mutations in the REarranged
      during Transfection (RET) tyrosine kinase gene have been associated with the
      development of a wide range of human associated cancers and Hirschsprung's
      disease. However, to what extent these mutations might affect bio-molecular
      functions remains unclear. In this article, the functionally significant
      mutations in RET were screened with the aid of various sequence and structure
      based in silico prediction methods. We mapped the deleterious mutants, modelled
      mutant proteins and deciphered the impact of mutations on drug binding mechanisms
      in the RET crystal structure of PDB ID: with the potential inhibitor vandetanib
      by docking analysis. Furthermore, molecular dynamics simulations were undertaken
      to understand the mechanistic action of cancer associated mutations in altering
      the protein kinase structure, dynamics, and stability. According to our results,
      the overall effect of V804M, M918T and S922Y were destabilizing and mostly alter
      the electrostatic component of the binding energy. Specifically, the mutation of
      gatekeeper residue valine 804 present in the ATP binding pocket affects the
      protein stability and confers resistance to the drug vandetanib, which was
      consistent with previously published experimental results. Overall, our findings
      may provide useful structural insights for in-depth understanding of the
      molecular mechanism underlying RET mutation and developing effective drugs. 

PMID- 24336965
TI  - Geographic determinants of gene flow in two sister species of tropical Andean
      frogs.
AB  - Complex interactions between topographic heterogeneity, climatic and
      environmental gradients, and thermal niche conservatism are commonly assumed to
      indicate the degree of biotic diversification in montane regions. Our aim was to
      investigate factors that disrupt gene flow between populations and to determine
      if there is evidence of downslope asymmetric migration in highland frogs with
      wide elevational ranges and thermal niches. We determined the role of putative
      impediments to gene flow (as measured by least-cost path (LCP) distances,
      topographic complexity, and elevational range) in promoting genetic divergence
      between populations of 2 tropical Andean frog sister species (Dendropsophus
      luddeckei, N = 114; Dendropsophus labialis, N = 74) using causal modeling and
      multiple matrix regression. Although the effect of geographic features was
      species specific, elevational range and LCP distances had the strongest effect on
      gene flow, with mean effect sizes (Mantel r and regression coefficients beta),
      between 5 and 10 times greater than topographic complexity. Even though causal
      modeling and multiple matrix regression produced congruent results, the latter
      provided more information on the contribution of each geographic variable. We
      found moderate support for downslope migration. We conclude that the climatic
      heterogeneity of the landscape, the elevational distance between populations, and
      the inability to colonize suboptimal habitats due to thermal niche conservatism
      influence the magnitude of gene flow. Asymmetric migration, however, seems to be
      influenced by life history traits. 

PMID- 24336967
TI  - Long-term clinical and anatomic outcome of birdshot chorioretinopathy.
AB  - IMPORTANCE: Birdshot chorioretinopathy is a chronic intraocular inflammatory
      disease with no uniform method to document long-term disease progression or
      response to treatment. OBJECTIVE: To examine the long-term visual, clinical, and
      anatomic outcomes of patients with birdshot chorioretinopathy. DESIGN, SETTING,
      AND PARTICIPANTS: A retrospective evaluation of 46 patients with birdshot
      chorioretinopathy treated at Moorfields Eye Hospital, London, England, was
      conducted. Medical records for a 19-year period (1993-2012) were reviewed.
      EXPOSURES: Patients received no treatment, short-term (<=1 year) treatment
      including local or systemic corticosteroids, or long-term (>1 year) treatment
      including systemic corticosteroids and second-line immunosuppressive agents. MAIN
      OUTCOMES AND MEASURES: Details regarding clinical and anatomic outcome, including
      best-corrected visual acuity, and visual field indices were evaluated. RESULTS:
      Ninety-two eyes of 46 patients were monitored for a mean (SE) of 57.2 (5.8)
      months (445 eye-years, 17% follow-up of >=10 years). Patients maintained a steady
      best-corrected visual acuity throughout the follow-up period. Some clinical
      indices correlated with transient worse best-corrected visual acuity, including
      presence of cataract (P = .05), foveal leakage on fluorescein angiography (P =
      .04), and increased central retinal thickness (P = .02). Serial visual field
      studies demonstrated that patients who received only short-term treatment had a
      worsening of their pattern standard deviation with time (Spearman correlation,
      0.57; P = .003); for those who received long-term treatment, the pattern standard
      deviation remained stable (Spearman correlation, -0.24; P = .26). CONCLUSIONS AND
      RELEVANCE: Our results suggest that central visual acuity can be maintained long
      term in patients with birdshot chorioretinopathy. Those who receive long-term
      immunosuppression appear to maintain better peripheral visual fields compared
      with patients who receive short-term treatment.

PMID- 24336966
TI  - The population history of endogenous retroviruses in mule deer (Odocoileus
      hemionus).
AB  - Mobile elements are powerful agents of genomic evolution and can be exceptionally
      informative markers for investigating species and population-level evolutionary
      history. While several studies have utilized retrotransposon-based insertional
      polymorphisms to resolve phylogenies, few population studies exist outside of
      humans. Endogenous retroviruses are LTR-retrotransposons derived from
      retroviruses that have become stably integrated in the host genome during past
      infections and transmitted vertically to subsequent generations. They offer
      valuable insight into host-virus co-evolution and a unique perspective on host
      evolutionary history because they integrate into the genome at a discrete point
      in time. We examined the evolutionary history of a cervid endogenous
      gammaretrovirus (CrERVgamma) in mule deer (Odocoileus hemionus). We sequenced 14
      CrERV proviruses (CrERV-in1 to -in14), and examined the prevalence and
      distribution of 13 proviruses in 262 deer among 15 populations from Montana,
      Wyoming, and Utah. CrERV absence in white-tailed deer (O. virginianus), identical
      5' and 3' long terminal repeat (LTR) sequences, insertional polymorphism, and
      CrERV divergence time estimates indicated that most endogenization events
      occurred within the last 200000 years. Population structure inferred from CrERVs
      (F ST = 0.008) and microsatellites (theta = 0.01) was low, but significant, with
      Utah, northwestern Montana, and a Helena herd being particularly differentiated.
      Clustering analyses indicated regional structuring, and non-contiguous clustering
      could often be explained by known translocations. Cluster ensemble results
      indicated spatial localization of viruses, specifically in deer from northeastern
      and western Montana. This study demonstrates the utility of endogenous
      retroviruses to elucidate and provide novel insight into both ERV evolutionary
      history and the history of contemporary host populations. 

PMID- 24336970
TI  - A structured physiotherapy treatment model can provide rapid relief to patients
      who qualify for lumbar disc surgery: a prospective cohort study.
AB  - OBJECTIVE: To evaluate a structured physiotherapy treatment model in patients who
      qualify for lumbar disc surgery. DESIGN: A prospective cohort study. PATIENTS:
      Forty-one patients with lumbar disc herniation, diagnosed by clinical assessments
      and magnetic resonance imaging. METHODS: Patients followed a structured
      physiotherapy treatment model, including Mechanical Diagnosis and Therapy (MDT),
      together with graded trunk stabilization training. Study outcome measures were
      the Oswestry Disability Index, a visual analogue scale for leg and back pain, the
      Tampa Scale for Kinesiophobia, the European Quality of Life in 5 Dimensions
      Questionnaires, the Zung Self-Rating Depression Scale, the Self-Efficacy Scale,
      work status, and patient satisfaction with treatment. Questionnaires were
      distributed before treatment and at 3-, 12- and 24-month follow-ups. RESULTS: The
      patients had already improved significantly (p < 0.001) 3 months after the
      structured physiotherapy treatment model in all assessments: disability, leg and
      back pain, kinesiophobia, health-related quality of life, depression and self
      efficacy. The improvement could still be seen at the 2-year follow-up.
      CONCLUSION: This study recommends adopting the structured physiotherapy treatment
      model before considering surgery for patients with symptoms such as pain and
      disability due to lumbar disc herniation.

PMID- 24336971
TI  - Inhibitory effects of mulberry fruit extract in combination with naringinase on
      the allergic response in IgE-activated RBL-2H3 cells.
AB  - In this study, we investigated the anti-allergic action of mulberry fruit extract
      (MFE) or MFE in combination with naringinase (MFEN) in IgE-activated RBL-2H3
      cells, and investigated the mechanisms responsible for the anti-allergic effects
      of MFEN. beta-hexosaminidase release assay was used to measure the amount of beta
      hexosaminidase released from the cells, and ELISA was used to measure the levels
      of tumor necrosis factor-alpha (TNF-alpha). We found that MFE significantly
      reduced the release of beta-hexosaminidase (IC(50), 10.59 mg/ml) and TNF-alpha
      (IC(50), 4.87 mg/ml). Moreover, MFEN enhanced the inhibitory effects on the
      release of beta-hexosaminidase (IC(50), 123.10 ug/ml) and TNF-alpha (IC(50),
      65.01 ug/ml). Furthermore, MFEN had no cytotoxicity at the concentration range
      used to exert the anti-allergic effects. In addition, we evaluated the effects of
      MFEN on the formation of pro-inflammatory lipid mediators, such as prostaglandin
      D(2) (PGD(2)), leukotriene C(4) (LTC(4)) and leukotriene B(4) (LTB(4)) using
      enzyme immunoassay (EIA) kits. MFEN markedly reduced the formation of PGD(2)
      (IC(50), 6.47 ug/ml) and LTC(4) (IC(50), 0.31 ug/ml), but not LTB(4) (IC(50),
      25.75 ug/ml). In mechanistic analyses, we measured the phosphorylation of Syk,
      Lyn and Fyn by immunoblot analysis. MFEN significantly inhibited the
      phosphorylation of Syk, but not that of Lyn or Fyn. MFEN also suppressed the
      phosphorylation of phospholipase C (PLC)gamma1/2, protein kinase C (PKC)delta,
      linker for activation of T cells (LAT), extracellular signal-regulated protein
      kinase (ERK)1/2, JNK, GRB2-associated binding protein 2 (Gab2), phosphoinositide
      3-kinase (PI3K), Akt, cytosolic phospholipase A2 and 5-lipoxygenase, as well as
      the expression of cyclooxygenase-2. In conclusion, these results suggest that
      MFEN exerts potent inhibitory effects on allergic response through the
      suppression of the activation of the FcepsilonRI signaling cascade. Our data
      demonstrating the anti-allergic effects of MFEN may provide further insight into
      the therapeutic application of MFEN or its use as a functional food.

PMID- 24336973
TI  - A dual coaxial nanocable sulfur composite for high-rate lithium-sulfur batteries.
AB  - Lithium-sulfur batteries have great potential for some high energy applications
      such as in electric vehicles and smart grids due to their high capacity, natural
      abundance, low cost and environmental friendliness. But they suffer from rapid
      capacity decay and poor rate capability. The problems are mainly related to the
      dissolution of the intermediate polysulfides in the electrolyte, and to the poor
      conductivity of sulfur and the discharge products. In this work, we propose a
      novel dual coaxial nanocable sulfur composite fabricated with multi-walled
      nanotubes (MWCNT), nitrogen-doped porous carbon (NPC) and polyethylene glycol
      (PEG), i.e. MWCNTs@S/NPC@PEG nanocable, as a cathode material for Li-S batteries.
      In such a coaxial structure, the middle N-doped carbon with hierarchical porous
      structure provides a nanosized capsule to contain and hold the sulfur particles;
      the inner MWCNTs and the outer PEG layer can further ensure the fast electronic
      transport and prevent the dissolution of the polysulfides into the electrolyte,
      respectively. The as-designed MWCNT@S/NPC@PEG composite shows good cycling
      stability and excellent rate capability. The capacity is retained at 527 mA h g(
      1) at 1 C after 100 cycles, and 791 mA h g(-1) at 0.5 C and 551 mA h g(-1) at 2 C
      after 50 cycles. Especially, the high-rate capability is outstanding with 400 mA
      h g(-1) at 5 C. 

PMID- 24336972
TI  - Notch1 is a potential therapeutic target for the treatment of human hepatitis B
      virus X protein-associated hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a highly lethal cancer with increasing
      worldwide incidence, and there are few therapeutics options available for
      patients with HCC. Thus, novel therapeutic targets for this disease are
      desperately needed. Chronic infection with hepatitis B virus (HBV) is the major
      risk factor for the development of HCC, while hepatitis B virus X protein (HBx)
      is essential for HBV-associated HCC. Based on our previous studies showing that
      HBx promoted hepatocarcinogenesis of the human non-tumor hepatic cell line L02
      and activated Notch1 signaling, Notch1 short hairpin RNA (shRNA) was utilized to
      inhibit Notch1 mRNA in the present study. We observed that Notch1 shRNA inhibited
      cell proliferation together with decreased activity of the Notch1 pathway in
      vitro, and also markedly suppressed tumor formation of L02/HBx cells in a BALB/c
      nude mouse model in vivo. Furthermore, the blockade of Notch1 was capable of
      arresting the cell cycle in the G0/G1 phase through the downregulation of
      CyclinD1, CDK4, E2F1 and the upregulation of p21 and Rb, while all of these
      factors were involved in the CyclinD1/CDK4 pathway. Inhibition of Notch1 by shRNA
      markedly promoted the apoptosis of L02/HBx cells via the caspase-9-caspase-3
      pathway. These data suggest that inhibition of Notch1 impairs the growth of human
      HBx-transformed L02 cells, and Notch1 may be a putative therapeutic target for
      human HBx-associated HCC.

PMID- 24336974
TI  - Expression, purification and characterization of a recombinant Tat47-57-Oct4
      fusion protein in Pichia pastoris.
AB  - The transcription factor, Oct-4, is involved in the self-renewal of
      undifferentiated embryonic stem cells, and is also significant in the
      reprogramming process and in the development of tumors. In the present study, the
      fusion protein, Tat47-57-Oct4, was secreted by the signal peptide of human serum
      albumin in Pichia pastoris under the control of alcohol oxidase promoter 1. The
      yield of recombinant Tat47-57-Oct4 fusion protein was ~210 mg/l. Following pilot
      scale fermentation, Tat47-57-Oct4 was purified by ammonium sulfate precipitation,
      Vivaflow 200 ultrafiltration and SP Sepharose fast flow chromatography in order
      to obtain 95.6% purity. Immunofluorescence analysis validated the ability of
      Tat47-57-Oct4 to cross the cell membrane. The results demonstrated that the
      experimental procedure developed in the present study could produce large
      quantities of active Tat47-57-Oct4 fusion protein from P. pastoris.

PMID- 24336975
TI  - The impact of cost-sharing schemes on drug compliance in Italy: evidence based on
      quantile regression.
AB  - OBJECTIVES: In this article we investigate the causal effect of cost-sharing
      schemes on compliance with statins in a quantile regression framework. METHODS:
      We use the health search CSD-LPD data, a longitudinal observational dataset
      containing computer-based patient records collected by Italian general
      practitioners. We exploit a series of natural experiments referring to several
      introductions of co-payment schemes in some of the Italian regions between 2000
      and 2009. We adopt an extended difference-in-differences approach to provide
      quantile estimates of the impact of co-payments on compliance. RESULTS: We find
      that (i) introduction of co-payments hurts residents of regions with worse
      quality and provision of health care; (ii) within these regions, co-payments were
      particularly harmful for high compliers; (iii) gender, clinical history and
      geographic residence are important determinants of compliance among poor
      compliers; (iv) compliance decreases with the potency and dosage of statins,
      particularly for poor compliers. CONCLUSIONS: In the presence of inefficient
      health-care provision, co-payments are harmful for drug compliance, and this is
      especially true for patients who are originally good compliers.

PMID- 24336978
TI  - Interaction between 8-hydroxyquinoline ruthenium(II) complexes and basic
      fibroblast growth factors (bFGF): inhibiting angiogenesis and tumor growth
      through ERK and AKT signaling pathways.
AB  - Angiogenesis is crucial for tumor growth. Thus, inhibiting angiogenesis
      represents a promising avenue for preventing tumor growth. This study
      investigated the anti-angiogenesis and anti-tumor effects of 8-hydroxyquinoline
      ruthenium(II) complexes [Ru(bpy)2(8-HQ)](+) (BQ) and [Ru(phen)2(8-HQ)](+) (PQ).
      The results showed that both compounds, especially PQ, suppressed the
      proliferation, migration, invasion, tube formation and microvessel growth of
      endothelial cells in vitro. PQ also inhibited tumor growth of human
      hepatocellular liver carcinoma cells (HepG2) in a mouse xenograft tumor model in
      vivo. To understand the mechanisms of how ruthenium(II) complexes disrupt bFGF
      induced angiogenesis and tumor growth, we have shown that (1) both compounds can
      interfere with the binding of bFGF to its cell surface receptors, thereby
      suppressing activation of bFGF-mediated signaling cascades; (2) PQ can induce
      tumor cell apoptosis. These effects might inhibit angiogenesis and tumor cell
      proliferation in tumor tissue. Taken together, our findings reveal that 8
      hydroxyquinoline ruthenium(II) complexes are specific inhibitors of bFGF-mediated
      angiogenesis, and may be a viable drug candidate in anti-angiogenesis and anti
      tumor therapies.

PMID- 24336977
TI  - "Green" functionalization of magnetic nanoparticles via tea polyphenol for
      magnetic resonance/fluorescent dual-imaging.
AB  - Tea polyphenol serves as an environmentally friendly ligand-exchange molecule to
      synthesize multifunctional metal-doped superparamagnetic iron oxide nanoparticles
      via a catechol-metal coordination interaction. The resultant particles not only
      exhibit excellent hydrophilicity and protein adsorption resistance, but also are
      applicable as magnetic resonance/fluorescent dual-imaging probes due to their
      high T2 relaxivity, autofluorescence and large cellular uptake.

PMID- 24336980
TI  - Transport properties of CuIn(1-x)Al(x)Se2/AZnO heterostructure for low cost thin
      film photovoltaics.
AB  - CuIn(1-x)Al(x)Se2 (CIASe) thin films were grown by a simple sol-gel route
      followed by annealing under vacuum. Parameters related to the spin-orbit
      (DeltaSO) and crystal field (DeltaCF) were determined using a quasi-cubic model.
      Highly oriented (002) aluminum doped (2%) ZnO, 100 nm thin films, were co
      sputtered for CuIn(1-x)Al(x)Se2/AZnO based solar cells. Barrier height and
      ideality factor varied from 0.63 eV to 0.51 eV and 1.3186 to 2.095 in the dark
      and under 1.38 A.M 1.5 solar illumination respectively. Current-voltage
      characteristics carried out at 300 K were confined to a triangle, exhibiting
      three limiting conduction mechanisms: Ohms law, trap-filled limit curve and SCLC,
      with 0.2 V being the cross-over voltage, for a quadratic transition from Ohm's to
      Child's law. Visible photodetection was demonstrated with a CIASe/AZO photodiode
      configuration. Photocurrent was enhanced by one order from 3 * 10(-3) A in the
      dark at 1 V to 3 * 10(-2) A upon 1.38 sun illumination. The optimized photodiode
      exhibits an external quantum efficiency of over 32% to 10% from 350 to 1100 nm at
      high intensity 17.99 mW cm(-2) solar illumination. High responsivity Rlambda ~
      920 A W(-1), sensitivity S ~ 9.0, specific detectivity D* ~ 3 * 10(14) Jones,
      make CIASe a potential absorber for enhancing the forthcoming technological
      applications of photodetection.

PMID- 24336981
TI  - Laser recall dermatitis.

PMID- 24336984
TI  - The Mobility Scale for Acute Stroke predicts discharge destination after acute
      hospitalization.
AB  - OBJECTIVE: To evaluate the predictive validity of the Mobility Scale for Acute
      Stroke (MSAS) in determining discharge destination (home or not home) after an
      acute stroke. DESIGN: Cohort study. SUBJECTS: Two-hundred and twenty-three
      patients with acute ischemic or intraparenchymal hemorrhagic, unilateral stroke
      METHODS: The MSAS was administered as part of the initial physical therapy
      examination. The Receiver Operating Characteristic determined the optimal MSAS
      cutoff score associated with discharge home. A multiple logistic regression
      equation with discharge destination as the criterion variable (home or not home)
      was conducted with age, length of stay and optimal MSAS cutoff score as
      covariates. RESULTS: Subjects were discharged home 35.9% (n = 80) and not home
      64.1% (n = 143) of the time. Mean age was 68.5 years (standard deviation 1.8).
      The ROC determined 26 to be the optimal cutoff score for the MSAS. Results of the
      multiple logistic regression equation indicated that controlling for age and
      length of stay, only the MSAS cutoff score of 26 reliably predicted discharge to
      home with an adjusted odds ratio of 57.79 with a 95% confidence interval of 20.09
      166.21. CONCLUSION: The MSAS may be useful for predicting discharge destination
      from the acute hospital after stroke.

PMID- 24336983
TI  - Adult height and prevalence of coronary artery calcium: the National Heart, Lung,
      and Blood Institute Family Heart Study.
AB  - BACKGROUND: Adult height has been hypothesized to be inversely associated with
      coronary heart disease; however, studies have produced conflicting results. We
      sought to examine the relationship between adult height and the prevalence of
      coronary artery calcium (CAC), a direct measure of subclinical atherosclerosis
      and surrogate marker of coronary heart disease. METHODS AND RESULTS: We evaluated
      the relationship between adult height and CAC in 2703 participants from the
      National Heart, Lung, and Blood Institute Family Heart Study who underwent
      cardiac computed tomography. We used generalized estimating equations to
      calculate the prevalence odds ratios for the presence of CAC (CAC>0) across sex
      specific quartiles of height. The mean age of the sample was 54.8 years, and
      60.2% of participants were female. There was an inverse association between adult
      height and CAC. After adjusting for age, race, field center, waist circumference,
      smoking, alcohol, physical activity, systolic blood pressure, antihypertensive
      medications, diabetes mellitus, diabetic medications, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, lipid-lowering medications,
      and income, individuals in the tallest quartile had 30% lower odds of having
      prevalent CAC. The odds ratios (95% confidence intervals) for the presence of CAC
      across consecutive sex-specific quartiles of height were 1.0 (reference), 1.15
      (0.86-1.53), 0.95 (0.73-1.22), and 0.70 (0.53-0.93), and P for trend<0.01. There
      was no evidence of effect modification for the relationship between adult height
      and CAC by age or socioeconomic status. CONCLUSIONS: The results of our study
      suggest an inverse, independent association between adult height and CAC.

PMID- 24336985
TI  - Characterization of the choroid-scleral junction and suprachoroidal layer in
      healthy individuals on enhanced-depth imaging optical coherence tomography.
AB  - IMPORTANCE: Accurate measurements of choroidal thickness (CT) using enhanced
      depth imaging optical coherence tomography (EDI-OCT) require a well-defined
      choroid-scleral junction (CSJ), which may appear in some eyes as a hyporeflective
      band corresponding to the suprachoroidal layer (SCL). OBJECTIVE: To identify
      factors associated with the presence and thickness of the SCL in healthy
      participants and determine how different CSJ boundary definitions impact CT
      measurements. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of EDI-OCT
      images obtained prospectively from 74 eyes of 74 controls (mean age, 68.6 years)
      from the Age-Related Eye Disease Study 2 Ancillary SDOCT Study. MAIN OUTCOMES AND
      MEASURES: The CSJ appearances were categorized as either having no visible SCL or
      a hyporeflective band corresponding to the SCL. Ocular parameters associated with
      the presence and thickness of the SCL were identified. Subfoveal CT was measured
      using 3 different posterior boundaries: (1) the posterior vessel border (vascular
      CT [VCT]), (2) inner border of the SCL (stromal CT [StCT]), and (3) inner border
      of the sclera (total CT [TCT]). Manual segmentation using custom software was
      used to compare VCT, StCT, and TCT across the macula. RESULTS The SCL was visible
      in 33 eyes (44.6%). Factors associated with SCL presence and thickness included
      hyperopic refractive error (R2 = 0.123; P = .045) and increased TCT (R2 = 0.215;
      P = .004), but not age, visual acuity, intraocular pressure, retinal foveal
      thickness, VCT, or StCT. In eyes where the SCL was not visible, mean [SD]
      subfoveal VCT was 222.3 [101.5] MUm and StCT and TCT were 240.0 [99.0] MUm, with
      a difference of 17.7 [16.0] MUm (P < .001). In eyes where the SCL was visible,
      mean [SD] subfoveal VCT, StCT, and TCT were 221.9 [83.1] MUm, 257.7 [97.3] MUm,
      and 294.1 [104.8] MUm, respectively, with the greatest difference of 72.2 [30.4]
      MUm between VCT and TCT (P < .001). All 3 CT measurements were significantly
      different along all points up to 3.0 mm nasal and temporal to the fovea.
      CONCLUSIONS AND RELEVANCE: A hyporeflective SCL is visible at the CSJ on EDI-OCT
      in nearly half of healthy individuals, and its presence correlates with
      hyperopia. Different posterior boundary definitions may result in significant
      differences in CT measurements and should be explicitly identified in future
      choroidal studies and segmentation algorithms.

PMID- 24336986
TI  - [Transitions].

PMID- 24336987
TI  - [Mental health in Quebec: new perspectives].

PMID- 24336988
TI  - [Mental healthcare system transformation: international tendencies and Quebec
      France perspectives].
AB  - This article is an overview of international tendencies on current mental
      healthcare transformation. It describes best practices based models and
      strategies aimed at improving efficiency of mental healthcare systems. To
      illustrate reforms in Quebec and France, the article reviews current literature
      and ongoing research on mental health care and service organization. During the
      last decade, primary care reinforcement, including best-practices and service
      integration, has been at the core of the mental healthcare system transformation.
      However, challenges regarding implementation appear to undermine the
      transformation's success. This article discusses mental healthcare services
      planning in order to improve their efficiency and allow the transfer of knowledge
      acquired through these reforms. 

PMID- 24336989
TI  - [The implementation of the Quebec Mental Health Action Plan: hands-on experience
      at the Maisonneuve-Rosemont hospital in Montreal].
AB  - The Mental Health Action Plan maps out the reorganization of mental health
      services in the province of Quebec. Accordingly, this paper presents the
      transformation process of the mental health program at the Maisonneuve-Rosemont
      hospital in Montreal. The authors discuss, on the one hand, the challenges that
      were met and, on the other hand, the model of care and organisational choices
      that were adopted. This article is divided in three parts. The first part
      describes the two main guiding principles underlying the Mental Health Action
      Plan. The second part examines the context surrounding the arrival of the Action
      Plan at the Maisonneuve-Rosemont Hospital. The third part describes the hospital
      transformation process that evolved in relation with: 1- the new centralized
      access points for mental health services; 2- the support for first line (or
      primary care) services; 3- the second line services for the specialized treatment
      of complex mental health problems. 

PMID- 24336990
TI  - [Primary mental health care teams for youths in the Monteregie region: a study of
      organizational models].
AB  - This qualitative study examines the organizational models of a primary mental
      health care team for youths in the Monteregie region. This region includes eleven
      teams working according to different modalities of functioning and within varied
      contexts. Data was collected in 2010 and 2011. The study describes current
      practices according to the perspective of members of these teams and modes of
      collaboration advocated by their different partners, a major issue when a team
      works within an integrated network of services. A taxonomy was elaborated in
      order to better appreciate the potential for improvement, and to highlight
      tangible avenues as much for management as for professionals of these teams. 

PMID- 24336991
TI  - [Specialized mental health services for the elderly: a pilot study of the
      evaluation process].
AB  - In Quebec, the Centre de sante et services sociaux (CSSS) Cavendish offers
      specialized services for the elderly with mental health problems (SSSM 60+) (Nour
      et al., 2011a). This article describes a targeted segment of the population
      reached (considering the exclusion criteria, only 50% of the elderly receiving
      services from the SSSM 60+ were followed). The article presents the model of
      individual changes relating to services, and explores the psychosocial mediators
      that influence the efficiency of services. This population experiences various
      psychosocial problems, the most important being mild to moderate symptoms of
      depression. Services and interventions by the SSSM 60+ team appear to increase
      significantly the therapeutic alliance and the feeling of empowerment in this
      clientele. Prioritizing these two concepts during service delivery appears to be
      an avenue to consider.

PMID- 24336992
TI  - [Efficacy of behavioural lifestyle interventions for weight management of
      psychiatric patients].
AB  - Significant weight gain is common in patients with psychiatric disorders taking
      antipsychotics, mood stabilisers and/or antidepressants. Psychiatric patients are
      at a higher risk of suffering from obesity and from the metabolic syndrome than
      the general population. One promising alternative to limiting weight gain
      involves modifying lifestyle behaviors. We reviewed the literature on behavioral
      weight management programs for this clientele. Of the 17 identified studies, 12
      reported a significant impact of the program on weight gain compared to usual
      care. The importance of offering weight management programs to psychiatric
      patients in outpatient settings is stressed. 

PMID- 24336993
TI  - [Profiles of agencies serving the homeless or those at risk of homelessness in
      the region of Montreal].
AB  - This article presents a study of organizations serving people who are homeless or
      at risk of becoming homeless (PHRH) in Montreal, as well as the determinants of
      their inter-organizational relationships. The study shows that greater inter
      organizational collaboration is needed, particularly within the network of health
      and social services (NHSS), to deal with the concomitant problems faced by PHRH.
      Among determinants that have an impact on the extent of inter-organizational
      relationships are the number of services offered, the appreciation of the
      relationships between organizations within the NHSS, and the ratio of Anglophones
      among the homeless and of individuals with gambling problems. 

PMID- 24336994
TI  - [Role of families of homeless persons with mental disorders : retrospective and
      prospective view of relationships].
AB  - This paper explores the experience of families supporting a homeless relative
      with mental illness. The authors investigate the types of support offered by
      families; they also examine the relational and personal dimensions which can
      support a redefining of the role and consequently a modulation of the level of
      support. Using a qualitative research, semi-structured interviews were realized
      with 14 family members. The results indicate that housing and the financial
      support are the types of support most frequently stopped while the emotional and
      the social support tend to be pursued. The control in the relation, the
      emotionalism and the perception of future appear as important element for the
      initiation of a role redefining process. 

PMID- 24336995
TI  - [Citizen accompaniment for community integration : a challenge for mental health
      ?].
AB  - APIC (Citizen Accompaniment Project for Community Integration) offers support for
      the social integration of people living with traumatic brain injury. The
      accompanying citizen meets the person three hours a week for a period of a year
      in order to offer assistance in the accomplishment of his/her projects and
      activities. This role confronts the accompanying citizen with many challenges
      that may put their mental health at risk. This article offers a reflection on
      this practice from the accompanying citizen's perspective. Five principles that
      can help better delimit and define citizen accompaniment are drawn from the
      results: 1) finding a "good distance" in the relationship to the accompanied
      person, 2) considering all of the actors in the process, 3) putting the
      accompanied person and their desires at the heart of the practice, 4) accepting
      not knowing everything, 5) being committed to the project and accepting it may
      transform you. 

PMID- 24336996
TI  - [Autism and social support in recently immigrated families : experience of
      parents from Maghreb].
AB  - This qualitative exploratory study examines the impact of an autism diagnosis on
      the social support networks of North African's parents recently immigrated to
      Quebec and having a child diagnosed with pervasive developmental disorder. Semi
      structured interviews were conducted with ten parents and participant observation
      took place during support meetings for the mothers. Our results highlight how the
      autism diagnosis transforms the parents' family and community networks, creating
      tensions and losses while also generating new links, sources of support. Group
      meetings between mothers of the same community experiencing the same problem are
      perceived particularly beneficial. The analysis of the relationship between
      professional service providers and families underlines how the development of a
      therapeutic alliance is threatened by major problems caused by administrative
      obstacles and intercultural communication difficulties. A greater awareness by
      health and social professionals of the interaction between the migratory context
      and the social network challenges associated with autism diagnostic for immigrant
      families would help ease these parents' loneliness and suffering. 

PMID- 24336997
TI  - [Mindfulness-Based Cognitive Therapy (MBCT) program with workers in an industrial
      setting: a pilot study].
AB  - The article describes the implementation of a pilot program in the tradition of
      secondary prevention interventions aimed at reducing the severity of stress
      symptom. Developed from the MBCT protocol, designed to prevent depressive
      relapse, its specificity lies in the adaptation of its teaching materials resting
      on the mindfulness meditation-cognition-psycho-education triptych. The
      transposition of the princeps model has been the subject of a controlled and
      randomized experimental trial performed on a non-clinical population working in
      an industrial environment to assess the effect of the aforesaid program on stress
      and associated symptoms. The outcomes suggest preliminary contributions as for
      the benefits generated on the psychic health of a group of workers. 

PMID- 24336998
TI  - [Co-therapy in intercultural clinical psychology].
AB  - Numerous clinicians practicing systemic psychotherapy have recognized the
      relevance of co-therapy, an intervention model involving at least two clinicians.
      Intercultural psychology and ethnopsychiatry have been inspired by the principles
      of co-therapy and have adapted it to the intercultural context. Our objective is
      to illustrate how co-therapy works in intercultural psychology, as it has been
      developed by the Specialized Psychological Services for Immigrants and for
      Refugees (SAPSIR). This intervention model facilitates the working through
      processes of mourning and of identity, important issues with migrant individuals.
      Finally, this practice cannot be reduced to the mere application of techniques
      including some cultural elements; it implies a special way of being in
      relationship with others, with oneself and with one's knowledge. 

PMID- 24336999
TI  - [Reflections on mentalization-based treatment and its adaptation for men
      presenting a narcissistic personality disorder and a not otherwise specified
      personality disorder].
AB  - Narcissistic personality disorder (NPD) and not otherwise specified personality
      disorder (borderline and narcissistic) are major mental health problems for men.
      These pathologies predispose patients to significant relational difficulties
      which are characterised by intense reactions to perceived threats to the self
      esteem and an impaired empathic ability. Understanding these disorders as affect
      dysregulation stimulated by shame, the author presents how patients in this
      context are prone to lose their capacity to mentalize. This article describes a
      specific individual and group mentalization-based treatment and its
      implementation for treating narcissistic men. Different reflections on the
      treatment, on empathy, as well as on the adaptation of this treatment for NPD
      patients are presented and illustrated with clinical vignettes. 

PMID- 24337000
TI  - [Factors associated with high exposure to psychotropic drugs in a Montreal
      catchment epidemiological area].
AB  - This article examine the associations between elevated exposure to psychotropic
      medications, presence of a diagnosis of mental illness, and sociodemographic
      characteristics in the adult population. A questionnaire was administered by
      interview to 2433 individuals aged 15 and over in the epidemiological catchment
      area of South-West Montreal. The determinants of psychotropic medication
      consumption were analyzed using bivariate analysis and multivariate logistic
      regression. A significant association was observed between the consumption of
      sleeping medications, anxiolytics, and antidepressants and being older, female,
      living alone, having a low level of education and income, being unemployed during
      the 12 months preceding the study, and presence of a mental disorder. An elevated
      exposure to different psychotropic medications (three or more) was reported in
      3.1% of the respondants. All things being equal, this increased with age, living
      alone, being unemployed over the course of the last year, and presence of a
      mental illness. The results suggest that it is necessary to consider social
      isolation and prevalence of mental illness in order to contextualize the elevated
      exposure to psychotropic medication. Polypharmacy may indeed pose important risks
      if it does not follow the logic of a coherent clinical intervention. 

PMID- 24337001
TI  - [" Co-occurrence of religious, superstitious, and delusional-like beliefs "].
AB  - Empirical data supporting a relationship between religious beliefs, superstitious
      beliefs and delusion-like beliefs remain sparse, even though these 3 types of
      beliefs have a common point: the fact that they rest on little or no proof. This
      suggests that these beliefs could be underlain by a common cognitive mechanism
      and thus, should be observed in the same individuals. To test this last
      hypothesis, we asked 95 participants without any psychiatric history to complete
      questionnaires of delusion-like, religious, and superstitious beliefs.
      Superstitious beliefs positively correlated with religious and delusion-like
      beliefs and thus tended to appear in the same individuals. However, delusion-like
      beliefs were only partially linked to religious beliefs. Therefore, their
      relation to religious beliefs remains ambiguous.

PMID- 24337003
TI  - [Witnessing: what is left].

PMID- 24337004
TI  - [Letter to the editor: an autistic person gets an honoris causa doctorate:
      illustration of the concept of the university-patient partnership].

PMID- 24337002
TI  - [A validation of the Social Provisions Scale: the SPS-10 items].
AB  - The Social Provisions Scale-10 item (SPS-10) is a shortened version of the Social
      Provisions Scale (Cutrona and Russell, 1987) validated in French (Echelle de
      provisions sociales) by Caron (1996). The Social Provisions Scale (SPS)
      originally consisted of six subscales to measure the availability of social
      support: emotional support or attachment, social integration, reassurance of
      worth, tangible help, orientation and opportunity for nurturance. Four items
      allowed measuring of each subscales, two formulated positively and two negatively
      for a total of 24 items. The SPS-10 retains five subscales, opportunity for
      nurturance was excluded and it only keeps the positively worded items, two items
      per dimension of support. The article presents its validation on a representative
      sample of 2433 people of the general population of the southwest region of
      Montreal. It has a strong concurrent validity with the original scale of 24 items
      (SPS) (r = 0.930). All its items are highly correlated with total scores and its
      internal consistency is excellent. The alpha for the global scale is 0.880 and
      the alphas for the five subscales ranged from 0.528 to 0.690. Its construct
      validity is also preserved. The SPS-10 has an independence of its dimensions with
      moderate correlations between the subscales ranging between 0.469 and 0.632 and
      its five subscales are more strongly related to the support global score (r
      minimum = 0.755 p <0.001 and r maximum = 0.835), indicating that they are also
      indicators of the availability of social provisions. An exploratory factor
      analysis allows finding almost the same factors structure than the French version
      of SPS. The SPS-10 explains 14.1% of the variance in psychological distress and
      retains 95% of the predictive power of the SPS-24 items and all its subscales are
      negatively correlated with psychological distress. It also explains 25.4% of the
      variance in quality of life and its predictive power is equivalent to the SPS-24
      items and all its subscales are positively correlated to QOL. The analyses
      suggest that the SPS-10 is a reliable and valid instrument for measuring the
      availability of social support with an administration time reduced by half. It is
      an excellent choice for epidemiological surveys.

PMID- 24337005
TI  - Chemoprotection by D-methionine against cisplatin-induced side-effects: insight
      from in vitro studies using human plasma.
AB  - Animal studies have shown that the nephrotoxicity and ototoxicity of the anti
      cancer drug cisplatin (CP) can be ameliorated by the co-administration with D
      methionine. The molecular mechanisms of this activity, however, are not well
      understood. Since CP is intravenously administered, the underlying chemistry may
      involve the interaction of CP-derived Pt-species with D-methionine in the
      bloodstream. Our previous studies have shown that the chemoprotective agents N
      acetyl-l-cysteine and sodium thiosulfate modulate the metabolism of CP in human
      plasma in vitro, albeit in a different manner. Using a metallomics approach, we
      show that the incubation of human plasma with D-methionine and CP (molar ratio of
      20 : 1) leads to the formation of a Pt-D-methionine complex independent of the
      order of addition. These results were corroborated by analogous experiments that
      were carried out using PBS-buffer instead of plasma. In addition, CP and D
      methionine were added simultaneously to PBS-buffer and samples were analyzed at
      certain time intervals by the same metallomics method and LC-ESI-MS over a ~21 h
      time period. Whereas the intermediate [Pt(NH3)Cl(D-methionine)](+) species was
      detected between 1-4 h, only the terminal [Pt(D-methionine)2](+) complex was
      present 21 h later. Combined, these studies demonstrate that in plasma and at the
      20 : 1 D-methionine : CP molar ratio, an early CP hydrolysis product reacts with
      D-methionine to form a 1 : 1 complex that is followed by the formation of a 2 : 1
      compound at a later time point. The formation of these Pt-D-methionine species
      may therefore play an important role in the processes by which D-methionine
      protects mammalian organisms against CP-induced toxicities.

PMID- 24337008
TI  - Development and entrainment of the colonic circadian clock during ontogenesis.
AB  - Colonic morphology and function change significantly during ontogenesis. In
      mammals, many colonic physiological functions are temporally controlled by the
      circadian clock in the colon, which is entrained by the central circadian clock
      in the suprachiasmatic nuclei (SCN). The aim of this present study was to
      ascertain when and how the circadian clock in the colon develops during the
      perinatal period and whether maternal cues and/or the developing pup SCN may
      influence the ontogenesis of the colonic clock. Daily profiles of clock genes
      Per1, Per2, Cry1, Cry2, Rev-erbalpha, Bmal1, and Clock expression in the colon
      underwent significant modifications since embryonic day 20 (E20) through
      postnatal days (P) 2, 10, 20, and 30 via changes in the mutual phasing among the
      individual clock gene expression rhythms, their relative phasing to the light
      dark regime, and their amplitudes. An adult-like state was achieved around P20.
      The foster study revealed that during the prenatal period, the maternal circadian
      phase may partially modulate development of the colonic clock. Postnatally, the
      absence and/or presence of rhythmic maternal care affected the phasing of the
      clock gene expression profiles in pups at P10 and P20. A reversal in the colonic
      clock phase between P10 and P20 occurred in the absence of rhythmic signals from
      the pup SCN. The data demonstrate ontogenetic maturation of the colonic clock and
      stress the importance of prenatal and postnatal maternal rhythmic signals for its
      development. These data may contribute to the understanding of colonic function
      related diseases in newborn children. 

PMID- 24337009
TI  - Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and
      activation of hepatic stellate cells.
AB  - Fluorofenidone (AKF-PD) is a novel pyridone agent. The purpose of this study is
      to investigate the inhibitory effects of AKF-PD on liver fibrosis in rats and the
      involved molecular mechanism related to hepatic stellate cells (HSCs). Rats
      treated with dimethylnitrosamine or CCl4 were randomly divided into normal,
      model, AKF-PD treatment, and pirfenidone (PFD) treatment groups. The isolated
      primary rat HSCs were treated with AKF-PD and PFD respectively. Cell
      proliferation and cell cycle distribution were analyzed by bromodeoxyuridine and
      flow cytometry, respectively. The expression of collagen I and alpha-smooth
      muscle actin (alpha-SMA) were determined by Western blot, immunohistochemical
      staining, and real-time RT-PCR. The expression of cyclin D1, cyclin E, and
      p27(kip1) and phosphorylation of MEK, ERK, Akt, and 70-kDa ribosomal S6 kinase
      (p70S6K) were detected by Western blot. AKF-PD significantly inhibited PDGF-BB
      induced HSC proliferation and activation by attenuating the expression of
      collagen I and alpha-SMA, causing G0/G1 phase cell cycle arrest, reducing
      expression of cyclin D1 and cyclin E, and promoting expression of p27(kip1). AKF
      PD also downregulated PDGF-BB-induced MEK, ERK, Akt, and p70S6K phosphorylation
      in HSCs. In rat liver fibrosis, AKF-PD alleviated hepatic fibrosis by decreasing
      necroinflammatory score and semiquantitative score, and reducing expression of
      collagen I and alpha-SMA. AKF-PD attenuated the progression of hepatic fibrosis
      by suppressing HSCs proliferation and activation via the ERK/MAPK and PI3K/Akt
      signaling pathways. AKF-PD may be used as a potential novel therapeutic agent
      against liver fibrosis. 

PMID- 24337011
TI  - Mina53, a novel molecular marker for the diagnosis and prognosis of gastric
      adenocarcinoma.
AB  - Mina53 is a direct novel target protein of Myc. The present study investigated
      the expression of mina53 and c-myc in gastric carcinoma and the relationship
      between Mina53 expression and clinicopathological features. The expression levels
      of mina53 and c-myc mRNA and protein in gastric cancers and the adjacent normal
      tissues from 12 patients were assessed by laser-capture microdissection (LCM)
      combined with quantitative polymerase chain reaction (qPCR) and western blotting,
      respectively. Immunohistochemical analysis was used to evaluate the expression of
      the Mina53 protein in normal gastric tissues (n=30), chronic atrophic gastritis
      without intestinal metaplasia (n=44), intestinal metaplasia (n=34), gastric
      dysplasia (n=36), intestinal-type gastric carcinoma (IGC) (n=30) and diffuse-type
      gastric carcinoma (DGC) (n=34). The correlation between expression of mina53 and
      patient survival time was also investigated. The expression levels of mina53 and
      c-myc mRNA in the gastric carcinomas were found to be higher when compared to
      these levels in the adjacent normal tissues. In addition, the expression levels
      of Mina53 and c-Myc protein in gastric carcinomas were higher when compared with
      levels in the adjacent normal epithelium. mina53 expression was significantly
      increased during gastric carcinogenesis and was correlated with different
      clinicopathological factors in IGC and DGC. The prognosis of patients with low
      expression of Mina53 was more favorable when compared to the prognosis of
      patients with high expression of Mina53. mina53 expression was gradually elevated
      during gastric carcinogenesis, and the overexpression of mina53 was correlated
      with different clinicopathological features between DGC and IGC cases.
      Furthermore, the prognosis of gastric carcinoma patients was significantly
      correlated with the expression of Mina53. 

PMID- 24337010
TI  - Functional consequences of EpCam mutation in mice and men.
AB  - Congenital tufting enteropathy (CTE) is a severe diarrheal disease of infancy
      characterized by villous changes and epithelial tufts. We previously identified
      mutations in epithelial cell adhesion molecule (EpCAM) as the cause of CTE. We
      developed an in vivo mouse model of CTE based on EpCAM mutations found in
      patients with the aim to further elucidate the in vivo role of EpCAM and allow
      for a direct comparison to human CTE. Using Cre-LoxP recombination technology, we
      generated a construct lacking exon 4 in Epcam. Epcam(Delta4/Delta4) mice and CTE
      patient intestinal tissue integrity was analyzed by histology using both light
      immunohistochemistry and electron microscopy. Epcam(Delta4/Delta4) mice
      demonstrate neonatal lethality and growth retardation with pathological features,
      including epithelial tufts, enterocyte crowding, altered desmosomes, and
      intercellular gaps, similar to human CTE patients. Mutant EpCAM protein is
      present at low levels and is mislocalized in the intestine of
      Epcam(Delta4/Delta4) mice and CTE patients. Deletion of exon 4 was found to
      decrease expression of both EpCAM and claudin-7 causing a loss of colocalization,
      functionally disrupting the EpCAM/claudin-7 complex, a finding for the first time
      confirmed in CTE patients. Furthermore, compared with unaffected mice, mutation
      of Epcam leads to enhanced permeability and intestinal cell migration, uncovering
      underlying disease mechanisms. 

PMID- 24337012
TI  - Survivin gene expression increases gastric cancer cell lymphatic metastasis by
      upregulating vascular endothelial growth factor-C expression levels.
AB  - The aim of this study was to investigate the correlation between the expression
      of survivin and vascular endothelial growth factor-C (VEGF-C) in gastric cancer
      and the pathway by which survivin may affect gastric cancer lymphatic metastasis.
      The study may provide novel targets for treating gastric cancer lymphatic
      metastasis and distal dissemination. Survivin and VEGF-C expression in gastric
      carcinoma and peri-carcinoma (2 cm away from the carcinoma) tissues, obtained
      from 195 patients who underwent curative gastrectomy surgery (130 cases presented
      with lymph node metastasis and 65 cases presented without metastasis), was
      examined immunohistochemically using a tissue microarray. Plasmids containing
      survivin and VEGF-C shRNA were constructed and transfected into SGC-7901 gastric
      cancer cells. The expression levels of the two genes were examined using western
      blot analysis and qPCR, and the results were statistically analyzed. The
      expression levels of survivin and VEGF-C were 51.3 and 55.4%, respectively, in
      gastric carcinoma. Survivin and VEGF-C were located mainly in the cytoplasm of
      the tumor cells. The expression levels of survivin and VEGF-C were significantly
      higher in patients with lymph node metastasis than in those without metastasis
      (P=0.008 and 0.001, respectively). Patients with high expression levels of
      survivin and VEGF-C showed significantly less favorable survival rates compared
      with patients with low expression levels of those two genes (P=0.003 and 0.039,
      respectively). Moreover, patients with co-expression of the two genes usually had
      a poorer prognosis (P=0.003). However, multivariate analysis demonstrated that
      neither of the two genes were an independent prognostic determinant. The levels
      of VEGF-C expression may be regulated by survivin expression. Conversely,
      inhibiting VEGF-C gene expression by shRNA did not reduce survivin expression at
      the mRNA or protein levels. Survivin and VEGF-C were expressed in gastric cancer
      cells and were significantly associated with lymphatic metastasis. Survivin may
      be a regulator of VEGF-C expression in gastric cancer cells, and is essential in
      invasion and lymphatic metastasis. Moreover, survivin may be able to serve as a
      chemotherapy target for gastric cancer.

PMID- 24337013
TI  - [Bone scintigraphy. German Guideline S1].
AB  - The purpose of this guideline is to provide comprehensive state-of-the-art
      information about indication and how to perform and analyze bone scintigraphy.
      Based upon pathophysiology and pharmacology current acquisition techniques
      including new methodologies are summarized followed by a detailed list of
      indications. In the main part all relevant practical aspects such as patient
      preparation, anamnestic information, appropriate choice and dosage of the
      radiopharmaceutical, and data acquisition including interventions are discussed.
      Data processing and analysis, interpretation, reporting and documentation are
      described in the next chapters. Quality control, typical pitfalls and a short
      outlook to future developments complete the guideline. 

PMID- 24337014
TI  - 18F, 11C and 68Ga in small animal PET imaging. Evaluation of partial volume
      correction methods.
AB  - AIM: The partial volume effect (PVE) significantly affects quantitative accuracy
      in PET. In this study we used a micro-hollow sphere phantom filled with 18F, 11C
      or 68Ga to evaluate different partial volume correction methods (PVC).
      Additionally, phantom data were applied on rat brain scans to evaluate PVC
      methods on in vivo datasets. METHODS: The four spheres (7.81, 6.17, 5.02, 3.90 mm
      inner diameter) and the background region were filled to give sphere-to
      background (sph/bg) activity ratios of 20 : 1, 10 : 1, 5 : 1 and 2 : 1. Two
      different acquisition and reconstruction protocols and three radionuclides were
      evaluated using a small animal PET scanner. From the obtained images the recovery
      coefficients (RC) and contrast recovery coefficients (CRC) for the different
      sph/bg ratios were calculated. Three methods for PVC were evaluated: a RC based,
      a CRC based and a volume of interest (VOI) based method. The most suitable PVC
      methods were applied to in vivo rat brain data. RESULTS: RCs were shown to be
      dependent on the radionuclide used, with the highest values for 18F, followed by
      11C and 68Ga. The calculated mean CRCs were generally lower than the
      corresponding mean RCs. Application of the different PVC methods to rat brain
      data led to a strong increase in time-activity curves for the smallest brain
      region (entorhinal cortex), whereas the lowest increase was obtained for the
      largest brain region (cerebellum). CONCLUSION: This study was able to show the
      importance and impact of PVE and the limitations of several PVC methods when
      performing quantitative measurements in small structures.

PMID- 24337015
TI  - [Preclinical research. Seal of approval translational medicine].

PMID- 24337016
TI  - 18F-FDG PET/CT uptake due to poly-L-lactic acid facial injections.

PMID- 24337017
TI  - Ultrasound guided percutaneous microwave ablation of hypofunctional thyroid
      nodules: evaluation by scintigraphic 99mTc-MIBI imaging.

PMID- 24337019
TI  - Low-cost and gram-scale synthesis of water-soluble Cu-In-S/ZnS core/shell quantum
      dots in an electric pressure cooker.
AB  - We report an electric pressure cooker for large-scale synthesis of water-soluble
      Cu-In-S/ZnS core/shell quantum dots. Low-cost thioglycolic acid and sodium
      citrate were used as the dual stabilizers. ~3 grams of quantum dots with a
      tunable emission from 545 to 610 nm and quantum yield up to 40% were obtained in
      a batch. 

PMID- 24337018
TI  - 4-Chloro-DL-phenylalanine protects against monocrotaline-induced pulmonary
      vascular remodeling and lung inflammation.
AB  - The present study was performed to investigate the effects of 4-chloro-DL
      phenylalanine (PCPA), a tryptophan hydroxylase (Tph) inhibitor (TphI), on
      pulmonary vascular remodeling and lung inflammation in monocrotaline (MCT)
      induced pulmonary arterial hypertension (PAH) in rats. Animal models of PAH were
      established using Sprague-Dawley (SD) rats by a single intraperitoneal injection
      of MCT (60 mg/kg). PCPA (50 or 100 mg/kg/day) was administered to the rats with
      PAH. On day 22, hemodynamic measurements and morphological observations of the
      lung tissues were performed. The levels of Tph-1 and serotonin transporter (SERT)
      in the lungs were analyzed by immunohistochemistry and western blot analysis. The
      expression of matrix metalloproteinase (MMP)-2 and MMP-9, tissue inhibitor of
      metalloproteinase (TIMP)-1 and TIMP-2 and inflammatory cytokines were assayed by
      western blot analysis. The activity of MMP-2 and MMP-9 was evaluated by gelatin
      zymography (GZ). MCT markedly promoted PAH, increased the right ventricular
      hypertrophy index, pulmonary vascular remodeling, lung inflammation and
      mortality, which was associated with the increased expression of Tph-1, SERT, MMP
      2/-9, TIMP-1/-2 and inflammatory cytokines. PCPA markedly attenuated MCT-induced
      pulmonary vascular remodeling and lung inflammation, inhibited the expression of
      Tph-1 and SERT and suppressed the expression of MMP-2/-9, TIMP-1/-2, interleukin
      1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and intercellular
      adhesion molecule-1 (ICAM-1). These findings suggest that the amelioration of MCT
      induced pulmonary vascular remodeling and lung inflammation by PCPA is associated
      with the downregulation of Tph-1, SERT, MMP/TIMP and inflammatory cytokine
      expression in rats.

PMID- 24337020
TI  - Phacomatosis pigmentokeratotica: a follow-up report with fatal outcome.

PMID- 24337023
TI  - On our own behalf.

PMID- 24337024
TI  - Alcohol-induced risk taking on the BART mediates alcohol priming.
AB  - RATIONALE: Hazardous drinking has been associated with risk taking and alcohol
      priming effects. However, the potential relationship between risk taking and
      priming has not been investigated. The Balloon Analogue Risk Task (BART) is a
      behavioural measure of risk taking which appears to be associated with drinking
      behaviour. However, alcohol's acute effects on BART performance are not clear,
      and the potentially mediating effect of alcohol-induced risk taking on priming
      has not been tested. OBJECTIVES: To assess the effects of a priming dose of
      alcohol on BART performance; to determine the predictive utility of the BART on
      drinking habits; and to identify whether alcohol-induced risk taking mediates
      alcohol priming (urge to drink). METHODS: A total of 142 participants provided
      data on drinking habits and trait-like impulsivity and sensation seeking. The
      BART was then completed after consuming alcohol (0.6 g/kg) or placebo (between
      subjects design). Baseline and post-drink measures of alcohol urge were also
      taken. RESULTS: Alcohol consumption increased urge to drink (priming) and risk
      taking on the BART. In the alcohol group only, risk taking on the BART predicted
      unique variance in weekly alcohol consumption and bingeing. Mediation analysis
      showed that risk taking following alcohol consumption mediated alcohol priming.
      CONCLUSIONS: This is the first study to show that alcohol acutely increases risk
      taking on the BART. Results suggest that social drinkers susceptible to alcohol
      induced risk taking may be more likely to drink excessively, perhaps due to
      increased urge to drink (priming).

PMID- 24337027
TI  - The popular and the "proper" performing arts.

PMID- 24337026
TI  - Drugs of abuse as memory modulators: a study of cocaine in rats.
AB  - RATIONALE: It has been proposed that drugs of abuse reinforce behavior partly, or
      wholly, because they facilitate learning by enhancing memory consolidation.
      Cocaine can clearly serve as a reinforcer, but its effect on learning has not
      been fully characterized. OBJECTIVES: To explore the effects of different
      regimens of pre- and post-training cocaine administration on win-stay and object
      learning. METHODS: Cocaine naive and cocaine pre-exposed (30 mg/kg/day, * 5 days
      followed by 7 days drug-free) male Sprague-Dawley rats received cocaine (0, 1,
      2.5, 7.5, or 20 mg/kg, i.p.) immediately following training on a win-stay task in
      a radial maze or following the sample phase of an object learning task. Win-stay
      performance was also assessed in tests of extinction and after a set shift.
      RESULTS: Post-training cocaine did not improve accuracy on the win-stay task and
      produced performance deficits at 20 mg/kg. These deficits were attenuated by
      prior cocaine exposure. There was indirect evidence of facilitated learning in
      extinction and set shift tests, but the effective dosage was different (2.5 and
      7.5 mg/kg, respectively). Post-training cocaine produced dose-dependent
      improvements in object learning. CONCLUSION: Post-training cocaine administration
      can facilitate learning, but this effect is highly dependent on the dose and the
      type of task employed.

PMID- 24337028
TI  - Practicing safe trad: why existing approaches to playing-related musculoskeletal
      disorders may not help the Irish traditional music community.
AB  - Playing-related musculoskeletal disorders (PRMDs) as they affect the Irish
      traditional music community is a topic which, to date, has received scant
      attention. This paper draws on data generated through a series of four focus
      group interview studies conducted at the Universities of Ulster and Limerick and
      involving 22 musicians. Specifically, this paper looks at the wider issue of
      identity within the Irish traditional music community and at how the complexities
      inherent in this have, perhaps, affected musicians in recognizing, relating to,
      and dealing with PRMDs. Whether or not the injuries affecting Irish traditional
      musicians are similar to or different from what other musicians experience, what
      this study shows is that the sense of self and discrete identity among the Irish
      traditional music community is so very strong that merely a "one size fits all"
      approach to addressing these issues is not likely to yield positive results.
      Health professionals therefore need to be sensitive to such factors when
      considering their management of PRMDs and to develop approaches along with the
      traditional music community that are cognisant of their identity as well as their
      needs. 

PMID- 24337025
TI  - Nicotine exposure during adolescence: cognitive performance and brain gene
      expression in adult heterozygous reeler mice.
AB  - RATIONALE: We have recently reported nicotine-induced stimulation of reelin and
      glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of
      heterozygous reeler mice (HRM), a putative animal model for the study of symptoms
      relevant to major behavioral disorders. OBJECTIVES: We aimed to evaluate long
      term behavioral effects and brain molecular changes as a result of adaptations to
      nicotine exposure in the developing HRM males. METHODS: Adolescent mice (pnd 37
      42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking
      schedule. As expected, no differences in total nicotine intake between WT (wild
      type) mice and HRM were found. RESULTS: Long-term behavioral effects and brain
      molecular changes, as a consequence of nicotine exposure during adolescence, were
      only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor
      cognitive performance were modulated to WT levels by subchronic exposure to
      nicotine during development. Furthermore, the expected reduction in the
      expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of
      HRM appeared persistently restored by nicotine. For brain-derived neurotrophic
      factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However,
      expression levels were increased by previous nicotine in brains from both
      genotypes. The mRNA encoding for nicotine receptor subunits (alpha7, beta2 and
      alpha4) did not differ between genotypes and as a result of previous nicotine
      exposure. CONCLUSION: These findings support the hypothesis of pre-existing
      vulnerability (based on haploinsufficiency of reelin) to brain and behavioral
      disorders and regulative short- and long-term effects associated with nicotine
      modulation.

PMID- 24337029
TI  - Median and ulnar neuropathies in U.S. Army Medical Command Band members.
AB  - PURPOSE: Musicians have been reported as having a high prevalence of upper
      extremity musculoskeletal disorders, including carpal tunnel syndrome. The
      purpose of this study was to determine the presence of median and ulnar
      neuropathies in U.S. Army Medical Command (MEDCOM) Band members at Fort Sam
      Houston, Texas. METHODS: Thirty-five MEDCOM Band members (30 males, 5 females)
      volunteered to participate. There were 33 right-handed musicians, and the mean
      length of time in the MEDCOM Band was 12.2 yrs (range, 1-30 yrs). Subjects
      completed a history form, were interviewed, and underwent a physical examination
      of the cervical spine and bilateral upper extremities. Nerve conduction studies
      of the bilateral median and ulnar nerves were performed. Electrophysiological
      variables served as the reference standard for median and ulnar neuropathy and
      included distal sensory latencies, distal motor latencies, amplitudes, conduction
      velocities, and comparison study latencies. RESULTS: Ten of the 35 subjects (29%)
      presented with abnormal electrophysiologic values suggestive of an upper
      extremity mononeuropathy. Nine of the subjects had abnormal median nerve
      electrophysiologic values at or distal to the wrist; 2 had bilateral abnormal
      values. One had an abnormal ulnar nerve electrophysiologic assessment at the
      elbow. Nine of these 10 subjects had clinical examination findings consistent
      with the electrophysiological findings. CONCLUSIONS: The prevalence of
      mononeuropathies in this sample of band members is similar to that found in
      previous research involving civilian musicians (20-36%) and far exceeds that
      reported in the general population. Prospective research investigating screening,
      examination items, and injury prevention measures in musicians appears to be
      warranted.

PMID- 24337030
TI  - Effect of midsole thickness of dance shoes on dynamic postural stability.
AB  - Landing from jumps is one of the main causes of injury within dance. A number of
      studies have reported a negative effect of shoe midsole thickness on lower limb
      kinematics during running due to the reduction in afferent sensory outputs from
      the foot's epithelium. The purpose of this study was to examine the influence of
      varying midsole thicknesses in dance shoes on dynamic postural stability during a
      single-leg landing. Twenty-eight female undergraduate dance participants
      volunteered for the study. They carried out three trials under four conditions:
      barefoot and in ballet flats (2 mm midsole thickness), jazz shoes (7 mm), and
      dance sneakers (30 mm). The task consisted of a single-leg forward jump over a
      hurdle at 50% of their maximal vertical jump height, landing on a force platform,
      and balancing for 3 seconds. The stability indices for vertical stability (VSI),
      anterior-posterior stability (APSI), medial-lateral stability (MLSI), and dynamic
      postural stability (DPSI) were calculated using Wikstrom's revised method.
      Significant differences were reported between the midsole thicknesses for both
      DPSI and VSI (p<0.01). No statistical differences were noted for the indices SPSI
      or MLSI. The present data agree with the running studies in that increased
      midsole thickness has a negative influence on landing stability. 

PMID- 24337031
TI  - Development of a performance anxiety scale for music students.
AB  - In the present research, the Performance Anxiety Scale for Music Students (PASMS)
      was developed in three successive studies. In Study 1, the factor structure of
      PASMS was explored and three components were found: fear of stage (FES),
      avoidance (AVD) and symptoms (SMP). The internal consistency of the subscales of
      PASMS, which consisted of 27 items, varied between 0.89 and 0.91. The internal
      consistency for the whole scale was found to be 0.95. The correlations among
      PASMS and other anxiety-related measures were significant and in the expected
      direction, indicating that the scale has convergent validity. The construct
      validity of the scale was assessed in Study 2 by confirmatory factor analysis.
      After several revisions, the final tested model achieved acceptable fits. In
      Study 3, the 14-day test-retest reliability of the final 24-item version of PASMS
      was tested and found to be extremely high (0.95). In all three studies, the whole
      scale and subscale scores of females were significantly higher than for males. 

PMID- 24337032
TI  - Anthropometry, somatotypes, and aerobic power in ballet, contemporary dance, and
      dancesport.
AB  - This study compared anthropometric variables, somatotypes, and aerobic capacity
      between three groups of dancers: classical ballet dancers (M 33, F 56),
      contemporary dancers (M 28, F 109), and dancesport dancers (M 30, F 30). The
      assumption was that different functional requirements should produce differences
      in the anthropometric and aerobic capacity variables among the three groups.
      Anthropometric data for body mass index (BMI) and somatotypes were measured. Body
      fat percentage was measured by dual-energy x-ray absorptiometry. Maximal oxygen
      consumption and aerobic power were measured during an incremental treadmill test
      until exhaustion. Dancesport athletes were taller compared with same gender
      contemporary dancers (p<0.05). Female ballet dancers had a lower body mass and
      BMI compared with their contemporary dance and dancesport equivalents (p<0.001).
      There was significant difference between dance styles in endomorphy (F2,221 =
      8.773, p<0.001) and mesomorphy (F2,221 = 21.458, p<0.001) scores. Dancesport
      dancers had significantly greater VO2max values (p<0.01). It was concluded that
      female contemporary dancers are generally more muscular than their ballet
      counterparts, while dancesport dancers are taller and heavier, less muscular,
      with slightly greater adioposity compared to the classical ballet dancers. Ballet
      dancers had the lowest body fat percentage, weight, and BMI values. Dancesport
      dancers had greater aerobic capacity than the ballet dancers. Based on this
      study, we conclude that dancers in these three styles differ in some aspects of
      anthropometric variables, somatotypes, and aerobic capacity, but we cannot say is
      it because of the training or selection or both. 

PMID- 24337033
TI  - Biomechanical research on bowed string musicians: a scoping study.
AB  - Performing arts biomechanics is concerned with quantifying the musculoskeletal
      demands of artistic tasks. The growing body of related research has prompted this
      scoping study, solely focused on quantitative research, to summarize the state of
      the science, identify knowledge gaps, and identify opportunities for future
      research. OBJECTIVES: To identify, summarize, and categorize quantitative
      research on the biomechanics of violin, viola, cello, and double bass players,
      using scoping study methodology. METHODS: Established scoping study methodology
      was used to identify and categorize existing research. We identified 74 articles
      for review. Of these, 34 met our scoping study criteria and were included in this
      study. RESULTS: Twenty-one of the 34 articles that met the scoping criteria were
      published since 2000. Investigations using electromyography (16 studies) and
      kinematics (15 studies) comprise the bulk of the research. Two studies employed
      force transducers for data collection. Violinists were the most frequently
      studied musicians (22 studies) and double bass players were the least (1 study).
      Fewer than half of the studies used solely professional musicians as their
      subjects (13 studies). CONCLUSIONS: This scoping study confirmed that
      quantitative biomechanical research into bowed string musicians has been
      performed with increasing frequency and that there are voids in the research,
      particularly in investigating mechanisms of injury and protective strategies.
      Currently, arts biomechanics research is largely descriptive in nature. There are
      few studies that investigate protective strategies, although it is expected that
      the field will progress to incorporate this type of research.

PMID- 24337034
TI  - Injury and the orchestral environment: part I. The role of work organisation and
      psychosocial factors in injury risk.
AB  - That orchestral musicians are exposed to a high risk of playing-related injury is
      well established, but despite this, little is known about how work organisation
      and psychosocial factors may contribute to this risk. Lack of research in this
      area is surprising considering the importance of these factors in managing
      occupational health risks in a wide range of other working populations. To
      address this, we conducted a qualitative study with the following aims: to
      investigate orchestral musicians' and managers' perceptions of those workplace
      environmental factors that contribute to injury, and to investigate the potential
      influence of work organisation and psychosocial factors on injury risk for
      orchestral musicians. Using a qualitative case-study methodology, in-depth, semi
      structured interviews were undertaken with 10 professional orchestral cellists (2
      casual and 8 full-time members) from a single Australian orchestra. After initial
      data analysis, further interviews were undertaken with a set of 5 orchestral
      management staff as a means of data triangulation. All data were analysed using a
      "themes-based" analysis of narrative approach. The findings indicate that
      musicians perceive that stress in the orchestral environment increases injury
      risk. The perceived stressors were divided into two broad categories:
      psychosocial injury risks, which included performance stress and interpersonal
      relationships, and combined psychosocial/physical injury risks such as work
      organisation and lack of control. This article evaluates the findings in terms of
      existing literature and makes recommendations for better management of
      environmental injury risk for orchestral musicians. 

PMID- 24337035
TI  - Can turnout measurements be used to predict physiotherapist-reported injury rates
      in dancers?
AB  - BACKGROUND: Research has suggested that dancers may be more at risk of injury
      when they excessively utilise non-hip components of turnout to compensate for
      deficits in hip external rotation when trying to achieve maximal total turnout.
      However, recently different measures of turnout have been cited in the literature
      as well as suggestions for derived variables to account for shortfalls in
      particular components of turnout. This study aimed to assess whether measurements
      of turnout can predict the number of injuries (0 or 1 injury, or 2+ injuries)
      over a 10-month period. METHODS: At the beginning of the academic year, 47
      female, full-time, contemporary dance students (mean age 19.9 +/- 2.51 yrs;
      height 1.65 +/- 0.05 cm; weight 56.23 +/- 6.51 kg) were screened as part of a
      biannual screening process. Measurements, summed of both legs, were obtained for
      passive hip external rotation (pER), total passive turnout (TPT), and total
      active turnout (TAT). From these, three further variables were derived:
      compensated turnout, muscular turnout, and active ER lag. At the end of 10
      months, the dancers' physiotherapist-reported and self-reported injuries were
      obtained. RESULTS: Binary regression analyses for the six turnout variables
      identified compensated and muscular values as having significant positive
      effects. For every 1% increase in compensated and muscular values, there was a
      corresponding 9% or 8.4% increase in the odds that the dancer would sustain 2 or
      more injuries compared to 0 or 1 injury. CONCLUSION: Screening compensated and
      muscular values may be useful to address shortfalls to prevent injuries in the
      future.

PMID- 24337036
TI  - BMI changes among marching artists: a longitudinal study.
AB  - In a series of longitudinal analyses, we examined body mass index (BMI) of drum
      and bugle corps performers at the beginning (Time 1) and end (Time 2) of a
      competitive season and again at a 1-year follow-up (Time 3). Utilizing an
      archival database, BMI data were recorded for 501 marching arts performers,
      representing four world-class drum and bugle corps. Significant reductions in BMI
      were found between Time 1 and Time 2 for performers in all sections (i.e., brass,
      percussion, and color guard). Archival data from 92 performers, representing
      three world-class drum and bugle units, revealed BMI significantly increased from
      Time 2 to Time 3. In an effort to identify possible personal influences on the
      changes in BMI found between Times 2 and 3, 50 performers from one drum and bugle
      corps provided archival data on a measures of performers' athletic identity
      (i.e., the strength and exclusivity of one's identification with the athlete
      role) along with BMI. Correlational analyses revealed that performers' athletic
      identity negatively related to BMI change from Time 1 and Time 3 and Times 2 and
      3 (i.e., stronger athletic identity, lower BMI change). Practical implications
      are discussed. 

PMID- 24337037
TI  - Epidemiology of health concerns among collegiate student musicians participating
      in marching band.
AB  - Participation in marching band requires intense physical and mental requirements,
      altered and potentially elevated biomechanical demands related to performing
      musical instruments while marching, routine exposures to elevated noise levels
      and at times hazardous weather conditions, and time commitments for practice and
      travel. Unfortunately, there are no known epidemiologic studies that
      systematically examine the perception of health-related consequences among
      college students participating in a collegiate marching band. There are no known
      studies that attempt to understand if the perceived consequences of marching band
      are different for students majoring in music compared to non-music major
      students. In response to this deficiency, this study collected and characterized
      occupational health patterns and concerns associated with participation in a
      collegiate marching band. Members of a large collegiate marching band (n=246/310,
      76%) responded to a 70-item epidemiologic survey. Results reveal patterns of
      health concerns and how they differ when compared across music majors vs non
      music majors and instrument groups. 

PMID- 24337038
TI  - Activity and loading influence the predicted bone remodeling around cemented hip
      replacements.
AB  - Periprosthetic bone remodeling is frequently observed after total hip
      replacement. Reduced bone density increases the implant and bone fracture risk,
      and a gross loss of bone density challenges fixation in subsequent revision
      surgery. Computational approaches allow bone remodeling to be predicted in
      agreement with the general clinical observations of proximal resorption and
      distal hypertrophy. However, these models do not reproduce other clinically
      observed bone density trends, including faster stabilizing mid-stem density
      losses, and loss-recovery trends around the distal stem. These may resemble
      trends in postoperative joint loading and activity, during recovery and
      rehabilitation, but the established remodeling prediction approach is often used
      with identical pre- and postoperative load and activity assumptions. Therefore,
      this study aimed to evaluate the influence of pre- to postoperative changes in
      activity and loading upon the predicted progression of remodeling. A strain
      adaptive finite element model of a femur implanted with a cemented Charnley stem
      was generated, to predict 60 months of periprosthetic remodeling. A control set
      of model input data assumed identical pre- and postoperative loading and
      activity, and was compared to the results obtained from another set of inputs
      with three varying activity and load profiles. These represented activity changes
      during rehabilitation for weak, intermediate and strong recoveries, and pre- to
      postoperative joint force changes due to hip center translation and the use of
      walking aids. Predicted temporal bone density change trends were analyzed, and
      absolute bone density changes and the time to homeostasis were inspected,
      alongside virtual X-rays. The predicted periprosthetic bone density changes
      obtained using modified loading inputs demonstrated closer agreement with
      clinical measurements than the control. The modified inputs also predicted the
      clinically observed temporal density change trends, but still under-estimated
      density loss during the first three postoperative months. This suggests that
      other mechanobiological factors have an influence, including the repair of
      surgical micro-fractures, thermal damage and vascular interruption. This study
      demonstrates the importance of accounting for pre- to postoperative changes in
      joint loading and patient activity when predicting periprosthetic bone
      remodeling. The study's main weakness is the use of an individual patient model;
      computational expense is a limitation of all previously reported iterative
      remodeling analysis studies. However, this model showed sufficient computational
      efficiency for application in probabilistic analysis, and is an easily
      implemented modification of a well-established technique.

PMID- 24337039
TI  - A gray pigmented band of the third fingernail with distal splitting.

PMID- 24337040
TI  - Knockdown of Bmi1 inhibits the stemness properties and tumorigenicity of human
      bladder cancer stem cell-like side population cells.
AB  - B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) is directly
      involved in cell growth, proliferation and self-renewal of cancer stem cells
      (CSCs). The aim of the present study was to assess the role of Bmi1 in the
      maintenance of stemness properties and tumorigenicity of human bladder CSC-like
      side population (SP) cells. SP cells were sorted by flow cytometry using Hoechst
      33342 staining. Bmi1 mRNA and protein expression in SP and non-SP (NSP) cells was
      analyzed by quantitative PCR, immunofluorescence and western blotting. The
      stemness properties of SP cells included cell proliferation, migration, self
      renewal, chemotherapy resistance and cell cycle progression were assessed. Tumor
      formation was also assessed in human bladder cancer xenografts after Bmi1
      silencing. The mRNA expression of Bmi1 was upregulated in SP cells when compared
      with that in the NSP cells. Knockdown of Bmi1 in SP cells resulted in inhibition
      of cell proliferation, migration and tumor sphere formation, enhanced sensitivity
      to cisplatin, and cell cycle arrest in the G0/G1 phase. Bmi1 knockdown inhibited
      cell cycle progression through derepression of the p16INK4a/p14ARF locus. Bmi1
      siRNA SP cells failed to produce tumors in recipient mice, while typical
      urothelial carcinoma formed from subcutaneously injected scramble-siRNA SP cells.
      Bmi1 is crucial for the maintenance of stemness properties and tumorigenicity of
      human bladder CSC-like cells. Bmi1 may be a potential therapeutic target for the
      eradication of CSCs in bladder cancer.

PMID- 24337042
TI  - Bioremediation via in situ microbial degradation of organic pollutants.
AB  - Contamination of soil and natural waters by organic pollutants is a global
      problem. The major organic pollutants of point sources are mineral oil, fuel
      components, and chlorinated hydrocarbons. Research from the last two decades
      discovered that most of these compounds are biodegradable under anoxic
      conditions. This has led to the rise of bioremediation strategies based on the in
      situ biodegradation of pollutants. Monitored natural attenuation is a concept by
      which a contaminated site is remediated by natural biodegradation; to evaluate
      such processes, a combination of chemical and microbiological methods are usually
      used. Compound specific stable isotope analysis emerged as a key method for
      detecting and quantifying in situ biodegradation. Natural attenuation processes
      can be initiated or accelerated by manipulating the environmental conditions to
      become favorable for indigenous pollutant degrading microbial communities or by
      adding externally breeded specific pollutant degrading microorganisms; these
      techniques are referred to as enhanced natural attenuation. Xenobiotic
      micropollutants, such as pesticides or pharmaceuticals, contaminate diffusively
      large areas in low concentrations; the biodegradation pattern of such
      contaminations are not yet understood. 

PMID- 24337043
TI  - Differences in content and organisational aspects of pulmonary rehabilitation
      programmes.
AB  - The aim was to study the overall content and organisational aspects of pulmonary
      rehabilitation programmes from a global perspective in order to get an initial
      appraisal on the degree of heterogeneity worldwide. A 12-question survey on
      content and organisational aspects was completed by representatives of pulmonary
      rehabilitation programmes that had previously participated in the European
      Respiratory Society (ERS) COPD Audit. Moreover, all ERS members affiliated with
      the ERS Rehabilitation and Chronic Care and/or Physiotherapists Scientific
      Groups, all members of the American Association of Cardiovascular and Pulmonary
      Rehabilitation, and all American Thoracic Society Pulmonary Rehabilitation
      Assembly members were asked to complete the survey via multiple e-mailings. The
      survey has been completed by representatives of 430 centres from 40 countries.
      The findings demonstrate large differences among pulmonary rehabilitation
      programmes across continents for all aspects that were surveyed, including the
      setting, the case mix of individuals with a chronic respiratory disease,
      composition of the pulmonary rehabilitation team, completion rates, methods of
      referral and types of reimbursement. The current findings stress the importance
      of future development of processes and performance metrics to monitor pulmonary
      rehabilitation programmes, to be able to start international benchmarking, and to
      provide recommendations for international standards based on evidence and best
      practice. 

PMID- 24337044
TI  - Maternal 25-hydroxyvitamin D levels in relation to offspring respiratory symptoms
      and infections.

PMID- 24337045
TI  - Trustworthy guidelines on severe asthma thanks to the ERS and ATS.

PMID- 24337046
TI  - International ERS/ATS guidelines on definition, evaluation and treatment of
      severe asthma.
AB  - Severe or therapy-resistant asthma is increasingly recognised as a major unmet
      need. A Task Force, supported by the European Respiratory Society and American
      Thoracic Society, reviewed the definition and provided recommendations and
      guidelines on the evaluation and treatment of severe asthma in children and
      adults. A literature review was performed, followed by discussion by an expert
      committee according to the GRADE (Grading of Recommendations, Assessment,
      Development and Evaluation) approach for development of specific clinical
      recommendations. When the diagnosis of asthma is confirmed and comorbidities
      addressed, severe asthma is defined as asthma that requires treatment with high
      dose inhaled corticosteroids plus a second controller and/or systemic
      corticosteroids to prevent it from becoming "uncontrolled" or that remains
      "uncontrolled" despite this therapy. Severe asthma is a heterogeneous condition
      consisting of phenotypes such as eosinophilic asthma. Specific recommendations on
      the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as
      well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics,
      antifungal agents and bronchial thermoplasty are provided. Coordinated research
      efforts for improved phenotyping will provide safe and effective biomarker-driven
      approaches to severe asthma therapy. 

PMID- 24337047
TI  - Selenium-enriched exopolysaccharides produced by Enterobacter cloacae Z0206
      alleviate adipose inflammation in diabetic KKAy mice through the AMPK/SirT1
      pathway.
AB  - Polysaccharides belong to a structurally diverse class of macromolecules, with
      the necessary flexibility for the precise regulatory mechanisms and high capacity
      for carrying biological information. On the basis of a previous study regarding
      the administration of selenium-enriched exopolysaccharides (Se-ECZ-EPS) produced
      by Enterobacter cloacae (E. cloacae) Z0206 which resulted in a reduction of blood
      glucose levels and showed significant anti-inflammatory and anti-diabetic
      effects, the present study was conducted to evaluate the effects and mechanism of
      EPS on the alleviation of fat inflammation in high-fat-diet (HFD) induced
      diabetic KKAy mice. The HFD induced-diabetic KKAy mice were gavaged once daily
      with EPS (0.2 mg/g body weight) or distilled water, while the C57BL/6J mice were
      gavaged with distilled water. Six weeks later visceral adipose tissue (VAT) was
      collected for quantified polymerase chain reaction (qPCR) and western blot (WB)
      analysis. The results showed that following supplementation with EPS, interleukin
      (IL) 6, IL1beta and tumor necrosis factor (TNF) alpha mRNA expression in VAT were
      significantly reduced, while Glut4, pAMPK and SirT1 protein expression were
      markedly increased when compared with KKAy mice gavaged with water. Furthermore,
      ATGL and HSL mRNA were also significantly decreased. Subsequently, 3T3-L1
      adipocytes were treated with insulin to induce insulin resistance to determine
      the mechanism by which EPS affects inflammation. Following the treatment of
      adipocytes with 100 nM insulin for 8 h, IL6 and TNFalpha mRNA expression were
      significantly increased, while the content of glucose uptake and Glut4 protein
      expression were significantly decreased. When treated with 100 nM insulin and 0.1
      mg/ml EPS, no significant change in IL6 and TNFalpha mRNA expression or glucose
      uptake were observed. However, when SirT1-siRNA or AMPKalpha1-siRNA was
      transfected into the 3T3-L1 adipocytes prior to treatment with insulin and EPS,
      there was a significant increase in IL6 and TNFalpha mRNA abundance. In
      conclusion, VAT inflammation and lipolysis in HFD-induced KKAy mice were
      significantly decreased following EPS usage. Moreover, EPS may alleviate VAT
      inflammation primarily through the AMPK/SirT1 pathway.

PMID- 24337048
TI  - Underestimated public health risks caused by overestimated VOC removal in
      wastewater treatment processes.
AB  - The uncontrolled release of volatile organic compounds (VOCs) from wastewater
      treatment plants (WWTPs) and the adverse health effects on the public have been
      of increasing concern. In this study, a lab-scale bioreactor was prepared to
      analyze the mass distribution of three aromatic (benzene, toluene, and xylenes)
      and four chlorinated VOCs (chloroform, carbon tetrachloride, trichloroethylene,
      and tetrachloroethylene) among the air, water and sludge phases in wastewater
      treatment processes. The VOC distribution through a full-scale WWTP in northern
      China was further investigated with respect to the effects of seasonal
      temperature variations and treatment technologies, followed by the cancer risk
      assessment using a steady-state Gaussian plume model (Industrial Source Complex)
      to simulate the atmospheric behaviors of the VOCs emitted from the WWTP. It was
      found that three aromatic hydrocarbons, notably benzene, were more readily
      released from the wastewater into the atmosphere, whereas the chlorinated
      compounds except chloroform were mainly present in the water phase through the
      treatment processes. The primary clarifier was the technology releasing high
      levels of VOCs into the atmosphere from the wastewater. The extents of
      volatilization or biodegradation, two important mechanisms to remove VOCs from
      wastewater, appeared to be determined by the physicochemical characteristics of
      the compounds, as the influence of treatment technologies (e.g., aeration) and
      seasonal temperature variations was rather limited. More importantly, the people
      living in the areas even more than 4 km away from the WWTP were still potentially
      exposed to cancer risks exceeding the regulatory threshold limit. The findings
      described the complex nature of VOC emissions from WWTPs and quantitatively
      indicated that the associated health impacts on the public near the WWTPs could
      be severely underestimated, whereas their treatment efficiencies by wastewater
      treatment technologies were overestimated. Instead of fully controlling the VOC
      release from WWTPs, the identification and abatement of important VOC species
      with regard to the atmospheric emission and health concerns is one possible
      alternative approach to effectively minimize the environmental and public health
      impacts by VOCs released from this particular source. 

PMID- 24337050
TI  - [Quality criteria for scientific collections within medical associations: the
      collections of the German Urological Association fullfill high requirements].
AB  - Quality criteria are necessary for the evaluation and rating of scientific
      collections of medical associations and are necessary for their development in
      order to argue within the scientific community or with other relevant actors. 

PMID- 24337049
TI  - Cooperative interaction of trp melastatin channel transient receptor potential
      (TRPM2) with its splice variant TRPM2 short variant is essential for endothelial
      cell apoptosis.
AB  - RATIONALE: Oxidants generated by activated endothelial cells are known to induce
      apoptosis, a pathogenic feature of vascular injury and inflammation from multiple
      pathogeneses. The melastatin-family transient receptor potential 2 (TRPM2)
      channel is an oxidant-sensitive Ca2+ permeable channel implicated in mediating
      apoptosis; however, the mechanisms of gating of the supranormal Ca2+ influx
      required for initiating of apoptosis are not understood. OBJECTIVE: Here, we
      addressed the role of TRPM2 and its interaction with the short splice variant
      TRPM2 short variant (TRPM2-S) in mediating the Ca2+ entry burst required for
      induction of endothelial cell apoptosis. METHODS AND RESULTS: We observed that
      TRPM2-S was basally associated with TRPM2 in the endothelial plasmalemma, and
      this interaction functioned to suppress TRPM2-dependent Ca2+ gating
      constitutively. Reactive oxygen species production in endothelial cells or
      directly applying reactive oxygen species induced protein kinase C-alpha
      activation and phosphorylation of TRPM2 at Ser 39. This in turn stimulated a
      large entry of Ca2+ and activated the apoptosis pathway. A similar TRPM2
      dependent endothelial apoptosis mechanism was seen in intact vessels. The protein
      kinase C-alpha-activated phosphoswitch opened the TRPM2 channel to allow large
      Ca2+ influx by releasing TRPM2-S inhibition of TRPM2, which in turn activated
      caspase-3 and cleaved the caspase substrate poly(ADP-ribose) polymerase.
      CONCLUSIONS: Here, we describe a fundamental mechanism by which activation of the
      trp superfamily TRPM2 channel induces apoptosis of endothelial cells. The
      signaling mechanism involves reactive oxygen species-induced protein kinase C
      alpha activation resulting in phosphorylation of TRPM2-S that allows enhanced
      TRPM2-mediated gating of Ca2+ and activation of the apoptosis program. Strategies
      aimed at preventing the uncoupling of TRPM2-S from TRPM2 and subsequent Ca2+
      gating during oxidative stress may mitigate endothelial apoptosis and its
      consequences in mediating vascular injury and inflammation.

PMID- 24337051
TI  - Preparation of solid silver nanoparticles for inkjet printed flexible electronics
      with high conductivity.
AB  - Silver nanoparticles (NPs) which could be kept in solid form and were easily
      stored without degeneration or oxidation at room temperature for a long period of
      time were synthesized by a simple and environmentally friendly wet chemistry
      method in an aqueous phase. Highly stable dispersions of aqueous silver NP inks,
      sintered at room temperature, for printing highly conductive tracks (~8.0 MUOmega
      cm) were prepared simply by dispersing the synthesized silver NP powder in water.
      These inks are stable, fairly homogeneous and suitable for a wide range of
      patterning techniques. The inks were successfully printed on paper and
      polyethylene terephthalate (PET) substrates using a common color printer. Upon
      annealing at 180  degrees C, the resistivity of the printed silver patterns
      decreased to 3.7 MUOmega cm, which is close to twice that of bulk silver. Various
      factors affecting the resistivity of the printed silver patterns, such as
      annealing temperature and the number of printing cycles, were investigated. The
      resulting high conductivity of the printed silver patterns reached over 20% of
      the bulk silver value under ambient conditions, which enabled the fabrication of
      flexible electronic devices, as demonstrated by the inkjet printing of conductive
      circuits of LED devices. 

PMID- 24337052
TI  - Cross-coupling/annulations of quinazolones with alkynes for access to fused
      polycyclic heteroarenes under mild conditions.
AB  - Ruthenium-catalyzed regioselective oxidative cross-coupling/annulations of
      quinazolones with alkynes were successfully developed for direct access to fused
      polycyclic heteroarenes. The transformation proceeded well with a broad substrate
      scope under mild conditions to achieve moderate to high yields. 

PMID- 24337053
TI  - [Prematurity: when can it be prevented?].

PMID- 24337054
TI  - [Central nervous system malformations and the presence of the MTHFR-C677T
      mutation in fetal blood].
AB  - PURPOSE: To evaluate the association between central nervous system (CNS)
      malformations and the C677T-MTHFR mutation in fetal blood. METHODS: A case
      control study was conducted to compare the MTHFR-C677T mutation detected in 78
      fetuses with CNS malformations and with 100 morphologically normal fetuses.
      Genomic DNA was extracted and purified from fetal blood using the Wizard(r)
      Genomic DNA Purification Kit (Promega Corp., Madison, WI, USA) according to
      manufacturer's protocol. The polymerase chain reaction (PCR) was used to assay
      the thermolabile MTHFR-C677T mutation. The gamma2 and the Fisher's exact tests
      were used for descriptive analysis and the Wilcoxon test was used for univariate
      analysis. Logistic regression analysis was performed to identify which variables
      were predictors of CNS malformation. RESULTS: Cases and controls were similar
      regarding maternal characteristics such as age and number of deliveries and
      abortions. The MTHFR-C677T mutation was detected in 20 cases (25.6%) and in 6
      controls in its heterozygous form (OR 10.3; 95%CI 3.3-32.2) and in 6 cases (7.7%)
      and in 1 control in its homozygous form (OR 12.3; 95%CI 1.3-111.1), and the
      differences were statistically significant. CONCLUSION: The presence of the MTHFR
      C677T mutation in fetal blood was consistent with a higher risk of CNS
      malformations, both in the heterozygous and homozygous forms.

PMID- 24337055
TI  - Does hyperglycemia in pregnancy change fetal kidney growth? A longitudinal
      prospective study.
AB  - PURPOSE: To measure fetal renal volume in normoglycemic and hyperglycemic
      pregnancies. METHODS: A longitudinal prospective study was conducted and included
      92 hyperglycemic and 339 normoglycemic pregnant women attended at the prenatal
      service of a hospital from Rio de Janeiro State. Ultrasound examinations were
      performed to estimate gestational age at baseline and the kidney volume was
      estimated using the prolate ellipsoid volume equation. RESULTS: Fetal kidney
      volume growth between normoglycemic and hyperglycemic pregnancies are
      significantly different. The fetal kidney volume growth in pregnancy is
      positively correlated with gestational age explained by these predictor
      equations, by group: normal renal volume = exp (6.186 + 0.09 * gestational week);
      hyperglycemic renal volume = exp (6.978 + 0.071 * gestational week) and an
      excessive growth pattern for hyperglycemic pregnancies may be established
      according to gestational age. CONCLUSION: This is important for early detection
      of abnormalities in pregnancy, particularly in diabetic mothers.

PMID- 24337056
TI  - [Quality of prenatal care in public and private services].
AB  - PURPOSE: To analyze prenatal care in public and private services. METHODS: A
      cross-sectional, retrospective and analytic study was conducted based on the
      audit of files of pregnant women who had given birth at a reference hospital for
      low risk cases in the area of Campos Gerais - Parana State, in the first semester
      of 2011. The Yates chi-squared test or exact Fisher test were used to determine
      the association between the lack of registration files for pregnant women
      regarding prenatal assistance in the public and private services, with the level
      of significance set at p <= 0.05. The quality of prenatal care was determined
      based on the percentile of non-registrations. RESULTS: A total of 500 prenatal
      files were analyzed. There was a significant attendance of six or more prenatal
      visits, with a larger proportion in the private service (91.9%). The laboratory
      and obstetric exams most frequently not registered in the public and in the
      private services were, respectively: hepatitis B (79.3 and 48.4%), hemoglobin and
      hematocrit values (35.6 and 21.8%), anti-HIV serology (29.3 and 12.9%), fetal
      movement (84.3 and 58.9%) and length (60.4 and 88.7%), edema verification (60.9
      and 54.8%), and fetal presentation (52.4 and 61.3%). The audit of the files of
      pregnant women allowed to determine the quality of the prenatal care provided and
      confirmed differences in assistance according to the place, showing excellent and
      good quality of private care, and regular public care for ultrasonography and
      blood type/Rh factor; regular quality of private care and poor quality of public
      care for urine tests and weight. For the other types of laboratory and obstetric
      exams and vaccines, the quality was poor or very poor in both types of services.
      CONCLUSION: The differences between the services showed that there is a need for
      actions aiming at the improvement of the prenatal care provided by public
      services.

PMID- 24337057
TI  - [Eosinophilia in peripheral blood of women with recurrent vaginal candidiasis].
AB  - PURPOSE: To quantify the number of defense cells and immunoglobulin E (IgE)
      levels in peripheral blood sampled from women with recurrent vulvovaginal
      candidiasis. METHODS: A cross-sectional study was conducted on 60 women, 40 with
      vulvovaginal candidiasis and 20 controls. The defense cells were identified using
      an impedance system combined with flow cytometry and total and specific IgE was
      measured by chemiluminescence. The Mann-Whitney test was used for nominal
      variables and the Spearman test was used to determine the correlation of IgE
      concentration and eosinophils in peripheral blood. RESULTS: The number of
      eosinophils in peripheral blood from patients with recurrent vulvovaginal
      candidiasis, 302.60 (+/- 253.07), was significantly higher compared to control,
      175.75 (+/- 109.24) (p=0.037). Serum levels of total and specific IgE were
      similar in the groups of women with and without recurrent vulvovaginal
      candidiasis (p=0.361). However, there was a moderate positive correlation between
      eosinophils and total serum IgE in the candidiasis group (r=0.25). CONCLUSION:
      Women with recurrent vulvovaginal candidiasis are more likely to have eosinophils
      in peripheral blood.

PMID- 24337058
TI  - [Interval for access to treatment for breast cancer in the Federal District,
      Brazil].
AB  - PURPOSE: To analyze the time between the first symptom and treatment in patients
      treated for breast cancer in public hospitals in the Federal District. METHODS:
      This was a cross-sectional analysis. We interviewed 250 women diagnosed with
      breast cancer treated in six hospitals of the State Department of Health of the
      Federal District from November 2009 to January 2011. The time intervals studied
      were the time between the detection of the symptoms and treatment subdivided into
      intervals until and after the first medical appointment. The variables were: age,
      menopausal status, color, educational level, average monthly household income,
      origin, reason for the initial consultation, staging, tumor size, laterality,
      metastasis to axillary lymph nodes, neoadjuvant chemotherapy, and type of
      surgery. The Mann-Whtney test was used to assess the association of these
      variables with the time intervals until treatment. RESULTS: The mean age was 52
      years, with a predominance of white women (57.6%), from the Federal District
      (62.4%), with a family income of up to 2 minimum wages (78%), and up to four
      years of schooling (52.4%). The staging of the disease ranged from II to IV in
      78.8% of the women. The time between the first symptom and treatment was 229 days
      (median). After detection of the first symptom, 52.9% of the women attended a
      consultation within 30 days and 88.8% took more than 90 days to start treatment.
      Women with elementary school education had a greater delay to the start of
      treatment (p=0.049). CONCLUSIONS: There was a significant delay to start
      treatment of women with breast cancer in public hospitals of the Federal
      District, suggesting that efforts should be made to reduce the time needed to
      schedule medical appointments and to diagnose and treat these patients.

PMID- 24337059
TI  - [Evaluation of image parameters of pelvic adnexal masses in tele-echography].
AB  - PURPOSE: To evaluate the sonographic parameters related to morphological
      characteristics of pelvic adnexal masses by obtaining two-dimensional images by
      an observer presence, forwarded electronically (via tele-ultrasound) in static
      and dynamic modes observers do not face (distance) for comparative analyzes inter
      intraobserver and to the validation of a second opinion. METHODS: From March to
      August 2010 were selected 50 patients with adnexal mass viewing of the pelvic
      ultrasound. They were subjected to ultrasound for abdominal and transvaginal
      routes. The images were captured in static and dynamic modes, electronically
      forwarded for evaluation of non-presence and two examiners evaluated according to
      morphological ultrasonographic parameters previously determined. RESULTS: The
      evaluators did not face in static and dynamic modes obtained almost perfect
      agreement for all morphological parameters with Kappa values between 0.6 and 0.8.
      There was no difference between the methods employed, except for the
      morphological parameter papillary projection in the static mode, in which the
      agreement was almost perfect (0.8) while in dynamic mode was substantial (0.6).
      CONCLUSIONS: The sonographic parameters of the features of adnexal masses pelvic
      sent by tele-ultrasound are capable of being validated for issuing a second
      opinion. There were no significant differences in the methodology used in the
      issue of tele-ultrasound images (static or dynamic) to characterize the
      composition of pelvic adnexal masses.

PMID- 24337060
TI  - [Confiability and reliability of an on-line version of the Female Sexual Function
      Index by test-retest].
AB  - PURPOSE: It was to test the validity and reliability of an online version of the
      Female Sexual Function Index (FSFI). METHODS: An online version of the FSFI was
      compared to the pen and paper traditional version. Physiotherapy students in
      three cities were randomly allocated to two groups - G-pp/ol (n=126) and G-ol/pp
      (n=147). G-pp/ol women replied to th FSFI using the traditional pen and paper
      method, while G-ol/pp women answered an online version of the same questionnaire.
      Data were collected ageing after 15 days, when G-pp/ol women answered the online
      version while G-ol/pp women answered on paper. All data were transferred to SPSS
      software. Demographic differences between the test two groups were determined by
      Student's t-test or Fisher exact (95%CI; p>0.05). Association and correlation
      between the responses of G-pp/ol and G-ol/pp were assessed for each sample by the
      t-test and Pearson's coefficient. An identical strategy was used for intragroup
      comparisons. RESULTS: A total of 273 women participated in the study and 28
      (10.2%) giving up the second collection. There were no demographic differences
      between groups. Fifteen of the 19 FSFI questions were associated and correlated
      between the two groups in both test and the retest. The intragroup analysis
      revealed that all FSFI questions and scores were associated and weakly correlated
      for the same group during both test and retest. CONCLUSION: The online version of
      the FSFI showed acceptable validity and reliability when compared to the paper
      version, and can justify the choice of this modality, especially in studies
      involving private questions.

PMID- 24337061
TI  - TWEAK/Fn14 signaling mediates gastric cancer cell resistance to 5-fluorouracil
      via NF-kappaB activation.
AB  - Chemoresistance is one of the most serious problems in the treatment of cancer.
      In the present study, we show that Fn14 promotes resistance to 5-fluorouracil (5
      FU) in gastric cancer (GC). We found that 5-FU treatment upregulated Fn14
      expression in various cancer cell lines, including GC cell lines, and that
      knockdown of Fn14 using shRNA accelerated 5-FU sensitivity. In contrast, Fn14
      overexpression or TWEAK treatment promoted resistance to 5-FU. Furthermore, we
      investigated the mechanisms underlying Fn14-mediated chemoresistance. We first
      revealed that 5-FU-mediated upregulation of Fn14 occurred as a result of NF
      kappaB activation, indicating that 5-FU-mediated NF-kappaB activation was the
      principal event underlying Fn14 upregulation and 5-FU resistance in GC. Taken
      together, our results suggest that Fn14 is a novel therapeutic target and that
      inhibition of Fn14 combined with 5-FU treatment may be an effective molecular
      therapeutic strategy to treat 5-FU-resistant gastric cancers. 

PMID- 24337062
TI  - Determining functional finger capabilities of healthy adults: comparing
      experimental data to a biomechanical model.
AB  - The human hand has a wide range of possible functional abilities that can change
      with age, disease, and injury, and can vary from individual to individual and
      subsequently can affect a person's quality of life. The objective of this work
      was to develop a theoretical model of the space that is reachable by the hand,
      weighted to represent three types of functionality, and to compare this model to
      an experimental data set obtained from a healthy hand population. A theoretical
      model, termed the Weighted Fingertip Space, was developed using 50th percentile
      published hand data and ranges of finger motion. The functional abilities
      calculated in the model were the abilities to position the fingertip pad, orient
      the fingertip pad, and apply directional forces through the fingertip pad at all
      the reachable points in space with respect to the palm. Following the development
      of this theoretical model, experimental data sets from nine individuals with
      healthy hands were obtained through motion capture techniques. The experimental
      data were then compared to the theoretical model. Comparisons between a 50th
      percentile theoretical model and a subject with a similar sized hand showed good
      agreement in weighting parameters and overall size and shape of the model spaces.
      The experimental data set from the entire sample, which ranged from the 2nd to
      95th percentile hand sizes, showed resultant models that, on average, reached
      smaller volumes of space, but yielded higher values of the functional measures
      within those volumes. Additionally, in comparison to the theoretical model, the
      variability of the experimental models showed that small changes in hand
      dimensions and ranges of motion of the finger joints had a large influence in the
      functional measures of the model. Combined, these results suggest that the
      modeling technique can calculate functional ability of the hand, but should be
      used on an individualized basis for evaluating changes in function (e.g.,
      rehabilitation). Further, scaling to hand size has the potential to yield
      "average" models for larger population samples. 

PMID- 24337063
TI  - The CCL5/CCR5 axis contributes to the perineural invasion of human salivary
      adenoid cystic carcinoma.
AB  - Salivary adenoid cystic carcinoma (SACC) has a unique tendency for perineural
      invasion (PNI), which results in tumor recurrence and poor prognosis. Recent
      studies have shown that the chemokine CCL5 and its receptor CCR5 play important
      roles in tumor invasion and metastasis. However, the role of the CCL5/CCR5 axis
      in the PNI of SACC has not been studied to date. In the present study, we
      evaluated the expression of CCL5 and CCR5 in SACC cases and nerve tissues, and
      performed a series of in vitro assays with the SACC cell line, SACC-83, to
      indicate the role of the CCL5/CCR5 axis in the PNI of SACC. We found that CCL5
      (35.9%; 23/64) and CCR5 (70.3%; 45/64) were positively expressed in SACC cases,
      and the expression of CCR5 was significantly associated with the PNI of SACC
      (P<0.05). We also found that SACC-83 cells expressed the functional receptor,
      CCR5, for the chemokine CCL5, as demonstrated by calcium mobilization and actin
      polymerization assays. Furthermore, we found that exogenous CCL5 significantly
      facilitated the migration, invasion and PNI activity of SACC-83 cells in vitro
      (P<0.05). Further study showed that the CCR5 inhibitor (maraviroc) effectively
      blocked the migration, invasion and PNI activity of SACC-83 cells with or without
      CCL5 stimulation (P<0.05). These results indicate that the CCL5/CCR5 axis plays a
      critical role in the PNI of SACC, and that antagonists against CCR5 may be an
      effective anti-PNI agent for SACC therapy.

PMID- 24337064
TI  - Changes in pro-inflammatory cytokines and body weight during 6-month risperidone
      treatment in drug naive, first-episode schizophrenia.
AB  - OBJECTIVE: The present study aimed to examine the changes in pro-inflammatory
      cytokines and body weight during 6-month risperidone treatment in drug naive,
      first-episode schizophrenia. METHODS: Sixty-two drug naive, first-episode
      schizophrenia (SZ group) and 60 healthy individuals (control group) were enrolled
      in the study. Serum interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha) levels, and body weight were measured at
      baseline for both groups, and repeated for the SZ group at five different time
      points during 6-month risperidone treatment. RESULTS: At baseline, serum IL
      1beta, IL-6, and TNF-alpha levels in the SZ group (53.28 +/- 12.62, 33.98 +/-
      14.13, 50.08 +/- 12.86 pg/mL, respectively) were significantly higher than those
      in the control group (23.49 +/- 15.27, 15.53 +/- 7.16, 32.12 +/- 15.23 pg/mL,
      respectively) (p's < 0.001). Within the SZ group, serum IL-1beta levels decreased
      significantly at 2 weeks (48.02 +/- 16.00 pg/mL, p < 0.01) and 1 month (44.70 +/-
      16.63 pg/mL, p < 0.001), but then gradually increased at 2 months (48.49 +/-
      18.87 pg/mL), 3 months (50.59 +/- 18.48 pg/mL) and 6 months (53.64 +/- 16.22
      pg/mL) to the levels comparable to baseline; serum IL-6 levels changed
      significantly over the course of treatment (p = 0.001), but reached the levels
      comparable to baseline at 6 months (37.13 +/- 13.23 pg/mL); serum levels of TNF
      alpha increased significantly at 3 months (55.02 +/- 16.69 pg/mL, p < 0.01) and 6
      months (58.69 +/- 13.57 pg/mL, p < 0.001); steady and significant weight gain was
      observed at each follow-up time point (p's < 0.001), from 56.71 +/- 9.25 kg at
      baseline to 62.72 +/- 9.53 kg at 6 months. CONCLUSIONS: Risperidone treatment is
      associated with changes in serum pro-inflammatory cytokines levels and weight.
      There is an initial anti-inflammatory effect that reduces with treatment,
      potentially due to its weight gain side effect.

PMID- 24337065
TI  - Inflammation: its role in schizophrenia and the potential anti-inflammatory
      effects of antipsychotics.

PMID- 24337066
TI  - Cosmetic dermatologic surgical training in US dermatology residency programs:
      identifying and overcoming barriers.
AB  - IMPORTANCE: The public and other medical specialties expect dermatologists who
      offer cosmetic dermatology services to provide competent care. There are numerous
      barriers to achieving cosmetic dermatology competency during residency. Many
      dermatology residents enter the workforce planning to provide cosmetic services.
      If a training gap exists, this may adversely affect patient safety. OBJECTIVES:
      To identify resources available for hands-on cosmetic dermatology training in US
      dermatology residency training programs and to assess program director (PD)
      attitudes toward cosmetic dermatology training during residency and strategies,
      including discounted pricing, used by training programs to overcome barriers
      related to resident-performed cosmetic dermatology procedures. DESIGN, SETTING,
      AND PARTICIPANTS: An online survey in academic dermatology practices among PDs of
      US dermatology residency programs. MAIN OUTCOMES AND MEASURES: Frequency of
      cosmetic dermatology devices and injectables used for dermatology resident hands
      on cosmetic dermatology training, categorizing PD attitudes toward cosmetic
      dermatology training during residency and describing residency-related discounted
      pricing models. RESULTS: Responses from PDs were received from 53 of 114 (46%) US
      dermatology residency programs. All but 3 programs (94%) offered hands-on
      cosmetic dermatology training using botulinum toxin, and 47 of 53 (89%) provided
      training with hyaluronic acid fillers. Pulsed dye lasers represented the most
      common laser use experienced by residents (41 of 52 [79%]), followed by Q
      switched Nd:YAG (30 of 52 [58%]). Discounted procedures were offered by 32 of 53
      (60%) programs, with botulinum toxin (30 of 32 [94%]) and fillers (27 of 32
      [84%]) most prevalent and with vascular lasers (17 of 32 [53%]) and hair removal
      lasers (12 of 32 [38%]) less common. Various discounting methods were used. Only
      20 of 53 (38%) PDs believed that cosmetic dermatology should be a necessary
      aspect of residency training; 14 of 52 (27%) PDs thought that residents should
      not be required to perform any cosmetic dermatology procedures. CONCLUSIONS AND
      RELEVANCE: Although almost every program provides hands-on cosmetic dermatology
      training, there are barriers to training, including patient preferences, costs of
      procedures and products, and PD attitudes toward cosmetic dermatology training.
      To promote patient safety, procedural competency is imperative.

PMID- 24337067
TI  - miRNA-302b suppresses human hepatocellular carcinoma by targeting AKT2.
AB  - miRNAs (miR) play a critical role in human cancers, including hepatocellular
      carcinoma. Although miR-302b has been suggested to function as a tumor repressor
      in other cancers, its role in hepatocellular carcinoma is unknown. This study
      investigated the expression and functional role of miR-302b in human
      hepatocellular carcinoma. The expression level of miR-302b is dramatically
      decreased in clinical hepatocellular carcinoma specimens, as compared with their
      respective nonneoplastic counterparts, and in hepatocellular carcinoma cell
      lines. Overexpression of miR-302b suppressed hepatocellular carcinoma cell
      proliferation and G1-S transition in vitro, whereas inhibition of miR-302b
      promoted hepatocellular carcinoma cell proliferation and G1-S transition. Using a
      luciferase reporter assay, AKT2 was determined to be a direct target of miR-302b.
      Subsequent investigation revealed that miR-302b expression was inversely
      correlated with AKT2 expression in hepatocellular carcinoma tissue samples.
      Importantly, silencing AKT2 recapitulated the cellular and molecular effects seen
      upon miR-302b overexpression, which included inhibiting hepatocellular carcinoma
      cell proliferation, suppressing G1 regulators (Cyclin A, Cyclin D1, CDK2) and
      increasing p27Kip1 phosphorylation at Ser10. Restoration of AKT2 counteracted the
      effects of miR-302b expression. Moreover, miR-302b was able to repress tumor
      growth of hepatocellular carcinoma cells in vivo. IMPLICATIONS: Taken together,
      miR-302b inhibits HCC cell proliferation and growth in vitro and in vivo by
      targeting AKT2.

PMID- 24337068
TI  - Actin-binding protein, Espin: a novel metastatic regulator for melanoma.
AB  - Espin is a multifunctional actin-bundling protein with multiple isoforms, and has
      special connections to hair cell stereocilia and microvillar specializations of
      sensory cells in the inner ear. However, there have been no reports showing the
      expression and function of Espin in cancers, including melanoma. Here, it is
      demonstrated that Espin expression is significantly increased in melanomas that
      spontaneously developed in RET-transgenic mice (RET-mice). Importantly, the
      invasion capacity of Espin-depleted Mel-ret melanoma cells derived from a tumor
      of the RET-mouse was dramatically less than that of control melanoma cells with
      reductions of lamellipodia, focal adhesion kinase (FAK), and GTP-Rac1 activities.
      Correspondingly, the ratio of metastatic foci in Espin-depleted Mel-ret melanoma
      cells was significantly less than that of control melanoma cells in an in vivo
      melanoma metastasis model. Moreover, Espin could be a novel biomarker of melanoma
      in humans, because our immunohistochemical analysis data reveal that percentages
      of Espin-positive cells in human primary and metastatic melanomas were
      significantly higher than that of cells in melanocytic nevi. Together, these
      results indicate that Espin is not only a metastatic regulator for melanoma but
      also a potential biomarker of disease progression. IMPLICATIONS: Actin-binding
      protein Espin is expressed in melanoma, affects metastasis, and is a potential
      target for melanoma therapy.

PMID- 24337069
TI  - Comparative microRNA profiling of prostate carcinomas with increasing tumor stage
      by deep sequencing.
AB  - MicroRNAs (miRNA) posttranscriptionally regulate gene expression and are
      important in tumorigenesis. Previous deep sequencing identified the miRNA profile
      of prostate carcinoma versus nonmalignant prostate tissue. Here, we generated
      miRNA expression profiles of prostate carcinoma by deep sequencing, with
      increasing tumor stage relative to corresponding nonmalignant and healthy
      prostate tissue, and detected clearly changed miRNA expression patterns. The
      miRNA profiles of the healthy and nonmalignant tissues were consistent with our
      previous findings, indicating a high fidelity of the method employed. In the
      tumors, quantitative real-time PCR (qRT-PCR) analysis of 40 paired samples of
      prostate carcinoma versus normal tissue revealed significant upregulation of miR
      20a, miR-148a, miR-200b, and miR-375 and downregulation of miR-143 and miR-145.
      Hereby, miR-375 increased from normal to organ-confined tumors (pT2 pN0),
      slightly decreased in tumors with extracapsular growth (pT3 pN0), but was then
      expressed again at higher levels in lymph node metastasizing (pN1) tumors. The
      sequencing data for miR-375 were confirmed by Northern blotting and qRT-PCR. The
      regulation for other selected miRNAs could, however, not be confirmed by qRT-PCR
      in individual tumor stages. MiR-200b, in addition to miR-200c and miR-375 reduced
      the expression of SEC23A. Interestingly, miR-375, found by sequencing in pT2
      upregulated by us and others in tumor versus normal tissue, and miR-15a, found by
      sequencing in pT2 and pT3 and in the metastasizing tumors, target the
      phosphatases PHLPP1 and PHLPP2, respectively. PHLPP1 and PHLPP2 dephosphorylate
      members of the AKT family of signal transducers, thereby inhibiting cell growth.
      Coexpression of miR-15a and miR-375 resulted in downregulation of PHLPP1/2 and
      strongly increased prostate carcinoma cell growth. IMPLICATIONS: These genomic
      data reveal relevant miRNAs in prostate cancer that may have biomarker and
      therapeutic potential.

PMID- 24337070
TI  - NEDD9 regulates 3D migratory activity independent of the Rac1 morphology switch
      in glioma and neuroblastoma.
AB  - Metastasizing tumor cells must transmigrate the dense extracellular matrix that
      surrounds most organs. The use of three-dimensional (3D) collagen gels has
      revealed that many cancer cells can switch between different modes of invasion
      that are characterized by distinct morphologies (e.g., rounded vs. elongated).
      The adhesion protein NEDD9 has the potential to regulate the switch between
      elongated and rounded morphologies; therefore, its role was interrogated in the
      invasion switch of glioblastoma and neuroblastoma tumors that similarly derive
      from populations of neural crest cells. Interestingly, siRNA-mediated depletion
      of NEDD9 failed to induce cell rounding in glioma or neuroblastoma cells,
      contrasting the effects that have been described in other tumor model systems.
      Given that Rac1 GTPase has been suggested to mediate the switch between elongated
      and rounded invasion, the functionality of the Rac1 morphology switch was
      evaluated in the glioma and neuroblastoma cells. Using both dominant-negative
      Rac1 and Rac1-specific siRNA, the presence of this morphologic switch was
      confirmed in the neuroblastoma, but not in the glioma cells. However, in the
      absence of a morphologic change following NEDD9 depletion, a significant decrease
      in the cellular migration rate was observed. Thus, the data reveal that NEDD9 can
      regulate 3D migration speed independent of the Rac1 morphology switch.
      IMPLICATIONS: NEDD9 targeting is therapeutically viable as it does not stimulate
      adaptive changes in glioma and neuroblastoma invasion.

PMID- 24337071
TI  - [Out-of-hospital emergency medicine in Germany, Austria and Switzerland :
      randomized prospective studies from 1990 to 2012].
AB  - BACKGROUND: Only randomized clinical trials can improve the outcome of life
      threatening injuries or diseases but observations from England and North America
      suggest that the number of such randomized clinical trials is decreasing. In this
      study contributions from German speaking countries with regards to randomized
      clinical trials in emergency medicine over the last 22 years were investigated.
      METHODS: The Medline database was searched from January 1990 to December 2012 for
      prospective randomized clinical trials in the prehospital setting using the
      criteria "cardiac arrest", "cardiopulmonary resuscitation", "multiple trauma",
      "hemorrhagic shock", "head trauma", "stroke" as well as myocardial infarction and
      emergency medical service. Only studies originating from Germany, Austria or
      Switzerland were included. RESULTS: A total of 474 studies were found and 25
      studies (5.3 %) fulfilled the inclusion criteria. In the last 22 years German
      speaking countries have published approximately one prospective, randomized,
      clinical trial per year on prehospital emergency medicine. The median number of
      patients included in the trials was 159 (minimum 16, maximum 1,219). Most (80 %)
      studies originated from Germany and most (64 %) studies were conducted by
      anesthesiology departments. Cardiac arrest was the most frequent subject of the
      investigated studies. Approximately 50 % of the studies had financial support
      from industrial companies. CONCLUSION: A significant increase or decrease in the
      number of prospective randomized clinical trials in the out-of-hospital setting
      could not be found in German speaking countries despite the fact that the
      absolute numbers of studies had increased. Only about one prospective, randomized
      clinical trial with an emergency medicine core tracer diagnosis originated from
      Germany, Austria and Switzerland per year.

PMID- 24337073
TI  - Electrochemical properties of CVD grown pristine graphene: monolayer- vs. quasi
      graphene.
AB  - We report the electrochemical properties of pristine monolayer, double layer and
      few-layer (termed quasi-) graphene grown via CVD and transferred using PMMA onto
      an insulating substrate (silicon dioxide wafers). Characterisation has been
      performed by Raman spectroscopy, optical spectroscopy, Atomic Force Microscopy
      and X-ray Photoelectron Spectroscopy, revealing 'true' pristine single-layer
      graphene (O/C of 0.05) at the former and pristine quasi-graphene at the latter
      (O/C of 0.07); the term "quasi-graphene" is coined due to the surface comprising
      on average 4-graphene-layers. The graphene electrodes are electrochemically
      characterised using both inner-sphere and outer-sphere redox probes with
      electrochemical performances of the graphene electrodes compared to other
      available graphitic electrodes, namely that of basal- and edge- plane pyrolytic
      graphite electrodes constructed from Highly Ordered Pyrolytic Graphite (HOPG),
      with information on heterogeneous rate constants (k(o)) obtained. The
      electrochemical rate constants are predominantly influenced by the electronic
      properties of the graphene surfaces. Monolayer graphene is found to exhibit slow
      heterogeneous electron transfer (HET) kinetics towards the redox probes studied,
      with HET rates ca. 2 and 8 times faster at quasi-graphene and HOPG respectively,
      relative to that of the monolayer graphene electrode. Critically contrasting the
      performance of monolayer graphene to quasi-graphene and HOPG electrodes reveals
      that increasing the number of graphene layers results in improved electrochemical
      properties, where in terms of the electrochemical reversibility of the probes
      studied: monolayer-graphene < quasi-graphene < HOPG, as governed by the
      respective HET electrochemical rate constants. Given that edge plane sites are
      the predominant origin of fast electron transfer kinetics at graphitic materials,
      the slow HET rates at pristine single-layer graphene electrodes are likely due to
      graphene's fundamental geometry, which comprises a small edge plane and large
      basal plane contribution. In the case of quasi-graphene and HOPG, they possess
      increasing global coverage of electrochemically reactive edge plane sites
      (respectively) and thus exhibit superior electrochemical performances over that
      of monolayer graphene. Last, the case of a double-layer graphene electrode is
      considered, which as a result of its fabrication possesses a large global
      coverage of edge plane like- sites/defects. In agreement with the former
      conclusions, the double-layered defect-graphene electrode is found to exhibit
      fast/favourable electrochemical properties, which is attributed to its large edge
      plane content (i.e. defect abundant graphene) and thus is further evidence that
      the electrochemical response is dependent on the density of edge plane sites at
      graphene based electrodes (influenced by the coverage of graphene-defects and the
      number of graphene layers). 

PMID- 24337072
TI  - [Epigenetics and pain].
AB  - Chronic pain affects approximately 20 % of adults worldwide and is often
      associated with a decrease in the quality of life and various comorbidities.
      Conventional analgesic therapies are frequently insufficient and sometimes lead
      to severe side effects. Therefore, great efforts are still being made to
      elucidate the signalling pathways in pain and to develop new, safe and effective
      therapies. Epigenetic mechanisms which interfere with the regulation of gene
      expression are involved in the pathogenesis of several diseases and are gaining
      increasing impetus in medical research. As they are also involved in pain
      processing, a modulation of these mechanisms might represent a novel option for
      the therapy of pain patients. 

PMID- 24337074
TI  - Evaluation of a novel personal nanoparticle sampler.
AB  - This work investigated the performance in terms of collection efficiency and
      aspiration efficiency of a personal sampler capable of collecting ultrafine
      particles (nanoparticles) in the occupational environment. This sampler consists
      of a cyclone for respirable particle classification, micro-orifice impactor
      stages with an acceleration nozzle to achieve nanoparticle classification and a
      backup filter to collect nanoparticles. Collection efficiencies of the cyclone
      and impactor stages were determined using monodisperse polystyrene latex and
      silver particles, respectively. Calibration of the cyclone and impactor stages
      showed 50% cut-off diameters of 3.95 MUm and 94.7 nm meeting the design
      requirements. Aspiration efficiencies of the sampler were tested in a wind tunnel
      with wind speeds of 0.5, 1.0, and 1.5 m s(-1). The test samplers were mounted on
      a full size mannequin with three orientations toward the wind direction (0
      degrees , 90 degrees , and 180 degrees ). Monodisperse oleic acid aerosols tagged
      with sodium fluorescein in the size range of 2 to 10 MUm were used in the test.
      For particles smaller than 2 MUm, the fluorescent polystyrene latex particles
      were generated by using nebulizers. For comparison of the aspiration efficiency,
      a NIOSH two-stage personal bioaerosol sampler was also tested. Results showed
      that the orientation-averaged aspiration efficiency for both samplers was close
      to the inhalable fraction curve. However, the direction of wind strongly affected
      the aspiration efficiency. The results also showed that the aspiration efficiency
      was not affected by the ratio of free-stream velocity to the velocity through the
      sampler orifice. Our evaluation showed that the current design of the personal
      sampler met the designed criteria for collecting nanoparticles <=100 nm in
      occupational environments. 

PMID- 24337075
TI  - Gankyrin is essential for hypoxia enhanced metastatic potential in breast cancer
      cells.
AB  - Hypoxia, a critical regulator of tumor growth and metastasis, induces the
      transcriptional activation of several pathways involved in proliferation,
      migration and invasion. Gankyrin was found to be overexpressed, and also promoted
      the metastasis in breast cancer cells, which is also involved in the regulation
      of hypoxia inducible factor-1 and hypoxia-inducible factor-1alpha. The present
      study showed that gankyrin mRNA and protein expression were increased under
      hypoxic conditions in the BT474 breast cancer cell line, accompanied with
      increased ability of cell migration and invasion. Lentivirus-mediated siRNA
      targeting gankyrin was transfected into BT474 cells. Wound-healing and transwell
      experiments showed that gankyrin deletion abrogated the increased migration and
      invasion of BT474 cells due to hypoxia. In addition, E-cadherin was found to be
      involved in the gankyrin induced invasion of breast cancer cells due to hypoxia.
      The present study indicated that gankyrin deletion abrogated the increased
      metastatic potential of breast cancer cells under hypoxic conditions partly
      through regulating E-cadherin, suggesting that an improved understanding of
      gankyrin may offer a potential therapeutic target for the treatment of human
      breast cancer metastasis.

PMID- 24337076
TI  - A love of dermatology.

PMID- 24337077
TI  - Examining the effects of initial smoking abstinence on response to smoking
      related stimuli and response inhibition in a human laboratory model.
AB  - RATIONALE: Research is needed on initial smoking abstinence and relapse risk.
      OBJECTIVE: This study aims to investigate the effects of different durations of
      initial abstinence on sensitivity to smoking-related stimuli and response
      inhibition in the context of a larger battery of outcome measures. METHODS:
      Smokers were randomly assigned to receive payment contingent on smoking
      abstinence across all 15 study days (15C) or just the final 2 days (2C). Smoking
      status and subject ratings were assessed daily. Participants completed fMRI
      sessions at baseline and day 14 during which they completed craving ratings after
      exposure to smoking-related and neutral stimuli and performed a response
      inhibition task. On day 15, participants completed a smoking preference session
      involving 20 exclusive choices between smoking and money. RESULTS: The payment
      contingencies were effective in producing greater smoking abstinence in the 15C
      vs. 2C conditions. Ratings of withdrawal decreased, while ratings of ease and
      confidence in abstaining increased in the 15C vs. 2C conditions across the 15-day
      study. 15C participants were less likely to choose the smoking option in the
      preference session. 15C participants reported greater reductions in craving
      compared to the 2C participants in the presence of smoking-related and neutral
      stimuli (i.e., decreases in generalized craving), but no differences were noted
      in cue reactivity per se or in response inhibition. CONCLUSIONS: Results
      systematically replicate prior observations that a period 2 weeks of initial
      abstinence decreases the relative reinforcing effects of smoking and improves
      other outcomes associated with relapse risk compared to the initial day or two of
      a cessation effort, and extends them by underscoring the importance of
      generalized rather than cue-induced craving in relation to relapse risk during
      the initial weeks of smoking cessation.

PMID- 24337080
TI  - AHVLA sets out a new structure for scanning surveillance.

PMID- 24337082
TI  - Plans to make BVD testing compulsory in Northern Ireland.

PMID- 24337078
TI  - Impact of escitalopram on vagally mediated cardiovascular function in healthy
      participants: implications for understanding differential age-related, treatment
      emergent effects.
AB  - RATIONALE: Black box warnings for young adults under the age of 25 years indicate
      that antidepressants may increase risk of suicide. While underlying mechanisms
      for age-related treatment effects remain unclear, vagally mediated cardiovascular
      function may play a key role. Decreased heart rate (HR) and an increase in its
      variability (HRV) improve one's capacity to adapt to environmental stress and
      attenuate risk for suicide. OBJECTIVES: Using a double blind, randomized, placebo
      controlled, crossover, experimental study, we examine whether a single dose of
      escitalopram (20 mg) attenuates cardiovascular responses to stress under
      experimental conditions and determine whether age moderates these effects.
      METHODS: Forty-four healthy females received a single dose of escitalopram (20
      mg) and placebo treatment separated by a 1-week interval (>5 half-lives). HR and
      high frequency HRV (HF HRV normalized units; 0.15-0.40 Hz) were measured during
      resting state and stress. RESULTS: While escitalopram attenuated the increase in
      HR and increased HF HRV, these moderate to large effects were only significant in
      participants over 25 years of age. No beneficial cardiovascular effects of
      escitalopram were observed in those under the age of 25. CONCLUSIONS:
      Maturational differences in the development of the prefrontal cortex--a critical
      region in the central network of autonomic control--may underpin these
      differential findings. This study provides a theoretical framework on which
      future research on treatment-emergent suicidality in clinical populations could
      be based.

PMID- 24337079
TI  - Evaluation of safety and tolerability, pharmacokinetics, and pharmacodynamics of
      BMS-820836 in healthy subjects: a placebo-controlled, ascending single-dose
      study.
AB  - RATIONALE: BMS-820836, a novel triple monoamine reuptake inhibitor, is an
      experimental monotherapy for sufferers of major depressive disorder who have had
      an inadequate response to an existing antidepressant treatment. OBJECTIVES: This
      study was conducted to evaluate the safety and tolerability, pharmacokinetics
      (PK), and serotonin transporter (SERT) and dopamine transporter (DAT) occupancy
      for single doses of BMS-820836 in healthy subjects. METHODS: Healthy subjects
      were assigned to seven BMS-820836 dose panels (0.025, 0.1, 0.5, 1, 2, 3, and 5
      mg; n = 8 each), in which subjects were randomly allocated 3:1 to a single BMS
      820836 dose or matched placebo. Serial blood samples were collected on Days 1, 2,
      3, 4, 7, and 14 to characterize the PK of BMS-820836. Following evaluation of the
      maximum tolerated dose, SERT occupancy was determined by applying [(11)C]DASB
      positron emission tomography (PET) after single-dose BMS-820836 (0.5 or 3 mg; n =
      3 each) and DAT occupancy by applying [(11)C]PE2I PET after single-dose BMS
      820836 (3 mg; n = 6). RESULTS: Single oral doses of BMS-820836 (0.025-3 mg) were
      generally safe and well tolerated. BMS-820836 had a median T max of 5.0-7.2 h and
      a mean apparent terminal T 1/2 of 34-57 h. Mean striatal SERT occupancies were 19
      +/- 9 % and 82 +/- 8 % after single doses of 0.5 and 3 mg BMS-820836,
      respectively. The mean striatal DAT occupancy was 19 +/- 9 % after a single 3 mg
      BMS-820836 dose. CONCLUSIONS: Single doses of BMS-820836 have meaningful SERT and
      DAT occupancy and demonstrate an acceptable safety and tolerability profile in
      healthy control subjects.

PMID- 24337085
TI  - Assuring the welfare of food animals.
AB  - There is a plethora of schemes for assuring the welfare of food animals but, with
      each having different standards and with incomplete coverage of all livestock
      sectors, consumers are confused about what they all mean. A debate at this year's
      BVA Congress highlighted the problem, and considered how it might be addressed at
      a farm and consumer level. Laura Honey reports. 

PMID- 24337086
TI  - Improving work-life balance: what can employers and employees do?
AB  - Effective time management can play a big part in reducing stress for busy vets,
      but too often miscommunication between practice employers and employees can make
      it harder to achieve a good work-life balance. Manuela Herrera reports on a
      session at the BVA Congress which considered what vets can do to facilitate
      better time management in practice. 

PMID- 24337087
TI  - Changing client behaviour.
AB  - Persuading someone to change their behaviour, whether for their own benefit or
      for that of their pet, is not an easy task. A session at this year's BVA Congress
      considered strategies to encourage people to 'change the norm'. Kathryn Clark
      reports. 

PMID- 24337088
TI  - One College - consulting on a new Royal Charter.
AB  - At its meeting in November, the RCVS Council agreed that the College should
      consult with the profession and the public on proposals for a new Royal Charter
      (see VR, November 23, 2013, vol 173, pp 493-496). Nick Stace, the RCVS's chief
      executive, explains why it believes a new charter is needed and what it aims to
      achieve. 

PMID- 24337089
TI  - New veterinary centre for Twycross Zoo.

PMID- 24337090
TI  - Suspected adverse events, 2012.
AB  - Increase in serious adverse events; Increase in reports involving products
      marketed under the Small Animal Exemption Scheme; Decrease in injection site
      reactions. These are some of the results from the surveillance work carried out
      by the pharmacovigilance unit at the Veterinary Medicines Directorate (VMD), as
      discussed by Giles Davis and colleagues.

PMID- 24337091
TI  - Digital dermatitis: tackling an emerging problem.

PMID- 24337092
TI  - Future of disease surveillance.

PMID- 24337093
TI  - Keeping exotic pets.

PMID- 24337094
TI  - Identifying risk factors for antimicrobial resistance.

PMID- 24337095
TI  - Origins of 'one medicine'.

PMID- 24337096
TI  - Reporting rabies risk.

PMID- 24337097
TI  - [Corrigendum] Temozolomide-induced modification of the CXC chemokine network in
      experimental gliomas.
AB  - After the publication of the article, the authors noted an error. The changes are
      as follows: In the initial and published version of Fig. 5, the data relied on
      triplicates in both the control (SCR) and treated (siCXCL2)conditions. In fact,
      the experiments were carried out in tetraplicates. However, the cells in one of
      the control (SCR) replicates died for unknown reasons. Thus, the data are here
      presented as the means +/- SEM calculated from triplicates in the SCR control
      condition and from tetraplicates in the siCXCL2 condition. Therefore, shown below
      is the corrected version of Fig. 5.

PMID- 24337098
TI  - Patch testing with formaldehyde 2.0% in parallel with 1.0% by the Swedish contact
      dermatitis research group.
AB  - In a multicentre study consecutively patch-tested dermatitis patients were tested
      simultaneously with 1.0% and 2.0% (w/v) formaldehyde in aqua applied with a
      micropipette (15 ul) to the filter paper disc in Finn Chambers (0.30 mg/cm(2) and
      0.60 mg/cm(2), respectively). A total of 2,122 dermatitis patients were patch
      tested. In all, 77 (3.6%) patients reacted positively to formaldehyde; 37 reacted
      only to 2.0%, 35 reacted to both concentrations and 5 patients reacted only to
      1.0%. Significantly more patients were thus diagnosed with contact allergy to
      formaldehyde with 2.0% compared to 1.0% (p < 0.001) without causing more irritant
      reactions. The detected number of isolated allergic reactions to the 2
      formaldehyde-releasers in the Swedish baseline series and not to formaldehyde
      itself raises the question whether quaternium-15 1.0% and diazolidinyl urea 2.0%
      should be present in the Swedish baseline series.

PMID- 24337099
TI  - Tuning of multifunctional Cu-doped ZnO films and nanowires for enhanced
      piezo/ferroelectric-like and gas/photoresponse properties.
AB  - The prospect of tuning and enhancing multiple properties of ZnO from optical,
      electrical, piezo to ferroelectricity/magnetism with Cu dopants will certainly
      spur the pursuit of facile doping methodology to immensely advance this field of
      research. Here, a one-step aqueous synthesis of Cu-doped ZnO nanostructured
      materials with effective controllability over the morphology (film to nanowire)
      and doping concentrations both on rigid and flexible substrates has been
      developed. High structural integrity Cu-doped ZnO films and nanowires were
      achieved without multiple/harsh post-processing which tends to degrade their
      functional properties. Comprehensive investigations of varying doping
      concentrations on the enhancement and tunability of room temperature
      piezo/ferroelectricity to gas/photosensing multifunctional properties were
      systematically reported for the first time. 

PMID- 24337100
TI  - Comparison among different high porosity stent configurations: hemodynamic
      effects of treatment in a large cerebral aneurysm.
AB  - Whether treated surgically or with endovascular techniques, large and giant
      cerebral aneurysms are particularly difficult to treat. Nevertheless, high
      porosity stents can be used to accomplish stent-assisted coiling and even
      standalone stent-based treatments that have been shown to improve the occlusion
      of such aneurysms. Further, stent assisted coiling can reduce the incidence of
      complications that sometimes result from embolic coiling (e.g., neck remnants and
      thromboembolism). However, in treating cerebral aneurysms at bifurcation termini,
      it remains unclear which configuration of high porosity stents will result in the
      most advantageous hemodynamic environment. The goal of this study was to compare
      how three different stent configurations affected fluid dynamics in a large
      patient-specific aneurysm model. Three common stent configurations were deployed
      into the model: a half-Y, a full-Y, and a crossbar configuration. Particle image
      velocimetry was used to examine post-treatment flow patterns and quantify root
      mean-squared velocity magnitude (VRMS) within the aneurysmal sac. While each
      configuration did reduce VRMS within the aneurysm, the full-Y configuration
      resulted in the greatest reduction across all flow conditions (an average of 56%
      with respect to the untreated case). The experimental results agreed well with
      clinical follow up after treatment with the full-Y configuration; there was
      evidence of thrombosis within the sac from the stents alone before coil
      embolization was performed. A computational simulation of the full-Y
      configuration aligned well with the experimental and in vivo findings, indicating
      potential for clinically useful prediction of post-treatment hemodynamics. This
      study found that applying different stent configurations resulted in considerably
      different fluid dynamics in an anatomically accurate aneurysm model and that the
      full-Y configuration performed best. The study indicates that knowledge of how
      stent configurations will affect post-treatment hemodynamics could be important
      in interventional planning and demonstrates the capability for such planning
      based on novel computational tools. 

PMID- 24337101
TI  - A reaction norm model for genomic selection using high-dimensional genomic and
      environmental data.
AB  - New methods that incorporate the main and interaction effects of high-dimensional
      markers and of high-dimensional environmental covariates gave increased
      prediction accuracy of grain yield in wheat across and within environments. In
      most agricultural crops the effects of genes on traits are modulated by
      environmental conditions, leading to genetic by environmental interaction (G *
      E). Modern genotyping technologies allow characterizing genomes in great detail
      and modern information systems can generate large volumes of environmental data.
      In principle, G * E can be accounted for using interactions between markers and
      environmental covariates (ECs). However, when genotypic and environmental
      information is high dimensional, modeling all possible interactions explicitly
      becomes infeasible. In this article we show how to model interactions between
      high-dimensional sets of markers and ECs using covariance functions. The model
      presented here consists of (random) reaction norm where the genetic and
      environmental gradients are described as linear functions of markers and of ECs,
      respectively. We assessed the proposed method using data from Arvalis, consisting
      of 139 wheat lines genotyped with 2,395 SNPs and evaluated for grain yield over 8
      years and various locations within northern France. A total of 68 ECs, defined
      based on five phases of the phenology of the crop, were used in the analysis.
      Interaction terms accounted for a sizable proportion (16 %) of the within
      environment yield variance, and the prediction accuracy of models including
      interaction terms was substantially higher (17-34 %) than that of models based on
      main effects only. Breeding for target environmental conditions has become a
      central priority of most breeding programs. Methods, like the one presented here,
      that can capitalize upon the wealth of genomic and environmental information
      available, will become increasingly important.

PMID- 24337102
TI  - Infusion of pharmaceutical-grade natural human C-reactive protein is not
      proinflammatory in healthy adult human volunteers.
AB  - RATIONALE: Baseline circulating concentrations of C-reactive protein (CRP) are
      significantly associated with cardiovascular disease risk in general populations.
      This modest association has been inappropriately conflated with causality, and it
      has been claimed that CRP is proatherogenic. Most of the known causative factors
      for atherosclerosis stimulate increased CRP production, but comprehensive genetic
      epidemiology studies provide no support for a pathogenic role of CRP. The
      reported proinflammatory effects of human CRP preparations on healthy cells in
      vitro and in healthy animals in vivo have all been produced by poorly
      characterized CRP preparations, demonstrably caused by impurities, or elicited by
      CRP made in recombinant Escherichia coli not by humans. None of the in vitro or
      animal findings have been reproduced with pure natural human CRP. Nevertheless,
      the strong proinflammatory effects of infusing recombinant bacterial CRP into
      humans have still been inappropriately ascribed to CRP. OBJECTIVE: To investigate
      the effects of infusion into healthy adult human volunteers of pure natural human
      CRP. METHODS AND RESULTS: Comprehensively characterized, pharmaceutical-grade,
      endotoxin-free, purified CRP, prepared to GMP standard from pooled normal human
      donor plasma was infused as an intravenous bolus in 7 healthy adult human
      volunteers at <=2 mg/kg to provide circulating CRP concentrations <=44 mg/L. No
      recipient showed any significant clinical, hematologic, coagulation, or
      biochemical changes, or any increase in proinflammatory cytokines or acute phase
      proteins. CONCLUSIONS: The human CRP molecule itself is not proinflammatory in
      healthy human adults.

PMID- 24337103
TI  - A universal ankle-foot prosthesis emulator for human locomotion experiments.
AB  - Robotic prostheses have the potential to significantly improve mobility for
      people with lower-limb amputation. Humans exhibit complex responses to mechanical
      interactions with these devices, however, and computational models are not yet
      able to predict such responses meaningfully. Experiments therefore play a
      critical role in development, but have been limited by the use of product-like
      prototypes, each requiring years of development and specialized for a narrow
      range of functions. Here we describe a robotic ankle-foot prosthesis system that
      enables rapid exploration of a wide range of dynamical behaviors in experiments
      with human subjects. This emulator comprises powerful off-board motor and control
      hardware, a flexible Bowden cable tether, and a lightweight instrumented
      prosthesis, resulting in a combination of low mass worn by the human (0.96 kg)
      and high mechatronic performance compared to prior platforms. Benchtop tests
      demonstrated closed-loop torque bandwidth of 17 Hz, peak torque of 175 Nm, and
      peak power of 1.0 kW. Tests with an anthropomorphic pendulum "leg" demonstrated
      low interference from the tether, less than 1 Nm about the hip. This combination
      of low worn mass, high bandwidth, high torque, and unrestricted movement makes
      the platform exceptionally versatile. To demonstrate suitability for human
      experiments, we performed preliminary tests in which a subject with unilateral
      transtibial amputation walked on a treadmill at 1.25 ms-1 while the prosthesis
      behaved in various ways. These tests revealed low torque tracking error (RMS
      error of 2.8 Nm) and the capacity to systematically vary work production or
      absorption across a broad range (from -5 to 21 J per step). These results support
      the use of robotic emulators during early stage assessment of proposed device
      functionalities and for scientific study of fundamental aspects of human-robot
      interaction. The design of simple, alternate end-effectors would enable studies
      at other joints or with additional degrees of freedom. 

PMID- 24337104
TI  - Metallomics--a new look for a New Year!

PMID- 24337106
TI  - Carbon monoxide releasing molecule-2 attenuated ischemia/reperfusion-induced
      apoptosis in cardiomyocytes via a mitochondrial pathway.
AB  - Carbon monoxide (CO) is an endogenous gaseous transmitter that exerts multi
      protection in ischemia/reperfusion (I/R) injury, but few experimental studies
      regarding CO on myocardial I/R-induced apoptosis, as well as its underlying
      mechanism have been conducted. The present study was designed to investigate
      whether CO released from CO-releasing molecule-2 (CORM-2) is capable of
      ameliorating myocardial I/R-induced apoptosis via a mitochondrial apoptotic
      pathway. Primary cultures of neonatal rat cardiomyocytes were randomly
      distributed into four groups: Control, I/R (cultured cardiomyocytes were
      subjected to 2 h simulated ischemia followed by 4 h reperfusion), CORM-2 and
      inactive CORM-2 (iCORM-2) groups (20 uM CORM-2 and 20 uM iCORM-2 were
      administered at the beginning of reperfusion following ischemia, respectively).
      Flow cytometric analysis showed that CORM-2 treatment significantly decreased
      apoptosis of cardiomyocytes triggered by simulated I/R. CORM-2 partially
      recovered mitochondrial respiration and ultrastructure alteration, and lowered
      caspase-3 expression and the release of cytochrome c. Furthermore, CORM-2 partly
      reduced BAK/BAX expression in mitochondria, as well as the BAX level in the
      cytoplasm. Cardioprotection is lost when CORM-2 is replaced by iCORM-2. CORM-2
      treatment, at the time of reperfusion, was concluded to attenuate myocardial I/R
      induced apoptosis. The protection mechanisms may be targeted to the mitochondria
      and involved in the inhibition of the BAK/BAX-mediated intrinsic pathway.

PMID- 24337105
TI  - Capsaicin induces apoptosis in PC12 cells through ER stress.
AB  - Capsaicin, the pungent agent in chili peppers, has been shown to act as a tumor
      suppressor in cancer. In our previous study, capsaicin was shown to induce
      apoptosis in the rat pheochromocytoma cell line (PC12 cells). Thus, the aim of
      the present study was to determine the potential mechanism by which capsaicin
      induces apoptosis. We treated PC12 cells with 50, 100 and 500 uM capsaicin and
      measured the reticular calcium content and expression of the reticular calcium
      transport systems. These results were correlated with endoplasmic reticulum (ER)
      stress markers CHOP, ATF4 and X-box binding protein 1 (XBP1), as well as with
      apoptosis induction. We observed that capsaicin decreased reticular calcium in a
      concentration-dependent manner. Simultaneously, expression levels of the
      sarco/endoplasmic reticulum pump and ryanodin receptor of type 2 were modified.
      These changes were accompanied by increased ER stress, as documented by increased
      stress markers. Thus, from these results we propose that in PC12 cells capsaicin
      induces apoptosis through increased ER stress.

PMID- 24337107
TI  - Competition for amino acids between Wolbachia and the mosquito host, Aedes
      aegypti.
AB  - The endosymbiont Wolbachia represents a promising method of dengue control, as it
      reduces the ability of the primary vector, the mosquito Aedes aegypti, to
      transmit viruses. When mosquitoes infected with the virulent Wolbachia strain
      wMelPop are fed non-human blood, there is a drastic reduction in mosquito
      fecundity and egg viability. Wolbachia has a reduced genome and is clearly
      dependent on its host for a wide range of nutritional needs. The fitness defects
      seen in wMelPop-infected A. aegypti could be explained by competition between the
      mosquito and the symbiont for essential blood meal nutrients, the profiles of
      which are suboptimal in non-human blood. Here, we examine cholesterol and amino
      acids as candidate molecules for competition, as they have critical roles in egg
      structural development and are known to vary between blood sources. We found that
      Wolbachia infection reduces total cholesterol levels in mosquitoes by 15-25%. We
      then showed that cholesterol supplementation of a rat blood meal did not improve
      fecundity or egg viability deficits. Conversely, amino acid supplementation of
      sucrose before and after a sheep blood meal led to statistically significant
      increases in fecundity of approximately 15-20 eggs per female and egg viability
      of 30-40%. This mosquito system provides the first empirical evidence of
      competition between Wolbachia and a host over amino acids and may suggest a
      general feature of Wolbachia-insect associations. These competitive processes
      could affect many aspects of host physiology and potentially mosquito fitness, a
      key concern for Wolbachia-based mosquito biocontrol.

PMID- 24337109
TI  - Parallelization of thermochemical nanolithography.
AB  - One of the most pressing technological challenges in the development of next
      generation nanoscale devices is the rapid, parallel, precise and robust
      fabrication of nanostructures. Here, we demonstrate the possibility to
      parallelize thermochemical nanolithography (TCNL) by employing five nano-tips for
      the fabrication of conjugated polymer nanostructures and graphene-based
      nanoribbons. 

PMID- 24337108
TI  - Previously undescribed plasmids recovered from activated sludge confer
      tetracycline resistance and phenotypic changes to Acinetobacter oleivorans DR1.
AB  - We used culture-dependent and culture-independent methods to extract previously
      undescribed plasmids harboring tetracycline (TC) resistance genes from activated
      sludge. The extracted plasmids were transformed into naturally competent
      Acinetobacter oleivorans DR1 to recover a non-Escherichia coli-based plasmid. The
      transformed cells showed 80-100-fold higher TC resistance than the wild-type
      strain. Restriction length polymorphism performed using 30 transformed cells
      showed four different types of plasmids. Illumina-based whole sequencing of the
      four plasmids identified three previously unreported plasmids and one previously
      reported plasmid. All plasmids carried TC resistance-related genes (tetL, tetH),
      tetracycline transcriptional regulators (tetR), and mobilization-related genes.
      As per expression analysis, TC resistance genes were functional in the presence
      of TC. The recovered plasmids showed mosaic gene acquisition through horizontal
      gene transfer. Membrane fluidity, hydrophobicity, biofilm formation, motility,
      growth rate, sensitivity to stresses, and quorum sensing signals of the
      transformed cells were different from those of the wild-type cells. Plasmid
      bearing cells seemed to have an energy burden for maintaining and expressing
      plasmid genes. Our data showed that acquisition of TC resistance through plasmid
      uptake is related to loss of biological fitness. Thus, cells acquiring antibiotic
      resistance plasmids can survive in the presence of antibiotics, but must pay
      ecological costs. 

PMID- 24337110
TI  - Inhibition of insulin-like growth factor-binding protein-3 signaling through
      sphingosine kinase-1 sensitizes triple-negative breast cancer cells to EGF
      receptor blockade.
AB  - The type I EGF receptor (EGFR or ErbB1) and insulin-like growth factor-binding
      protein-3 (IGFBP-3) are highly expressed in triple-negative breast cancer (TNBC),
      a particularly aggressive disease that cannot be treated with conventional
      therapies targeting the estrogen or progesterone receptors (ER and PR), or HER2.
      We have shown previously in normal breast epithelial cells that IGFBP-3
      potentiates growth-stimulatory signaling transduced by EGFR, and this is mediated
      by the sphingosine kinase-1 (SphK1)/sphingosine 1-phosphate (S1P) system. In this
      study, we investigated whether cotargeting the EGFR and SphK1/S1P pathways in
      TNBC cells results in greater growth inhibition compared with blocking either
      alone, and might therefore have novel therapeutic potential in TNBC. In four TNBC
      cell lines, exogenous IGFBP-3 enhanced ligand-stimulated EGFR activation,
      associated with increased SphK1 localization to the plasma membrane. The effect
      of exogenous IGFBP-3 on EGFR activation was blocked by pharmacologic inhibition
      or siRNA-mediated silencing of SphK1, and silencing of endogenous IGFBP-3 also
      suppressed EGF-stimulated EGFR activation. Real-time analysis of cell
      proliferation revealed a combined effect of EGFR inhibition by gefitinib and
      SphK1 inhibition using SKi-II. Growth of MDA-MB-468 xenograft tumors in mice was
      significantly inhibited by SKi-II and gefitinib when used in combination, but not
      as single agents. We conclude that IGFBP-3 promotes growth of TNBC cells by
      increasing EGFR signaling, that this is mediated by SphK1, and that combined
      inhibition of EGFR and SphK1 has potential as an anticancer therapy in TNBC in
      which EGFR and IGFBP-3 expression is high.

PMID- 24337111
TI  - Detailed identification of fatty acid isomers sheds light on the probable
      precursors of triacylglycerol accumulation in photoautotrophically grown
      Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii is a model alga for studying triacylglycerol (TAG)
      accumulation in the photosynthetic production of biofuel. Previous studies were
      conducted under photoheterotrophic growth conditions in medium supplemented with
      acetate and/or ammonium. We wanted to demonstrate TAG accumulation under truly
      photoautotrophic conditions without reduced elements. We first reidentified all
      lipid components and fatty acids by mass spectrometry, because the currently used
      identification knowledge relies on data obtained in the 1980s. Accordingly,
      various isomers of fatty acids, which are potentially useful in tracing the flow
      of fatty acids leading to the accumulation of TAG, were detected. In strain
      CC1010 grown under photoautotrophic conditions, TAG accumulated to about 57.5
      mol% of total lipids on a mole fatty acid basis after the transfer to nitrogen
      deficient conditions. The content of monogalactosyl diacylglycerol,
      sulfoquinovosyl diacylglycerol, and phosphatidylglycerol decreased drastically.
      The accumulated TAG contained 16:0 as the major acid and 16:4(4,7,10,13),
      18:2(9,12), and 18:3(9,12,15), which are typically found in chloroplast lipids.
      Additionally, 18:1(11) and 18:3(5,9,12), which are specific to extrachloroplast
      lipids, were also abundant in the accumulated TAG. Photosynthesis and respiration
      slowed markedly after the shift to nitrogen-deficient conditions. These results
      suggest that fatty acids for the production of TAG were supplied not only from
      chloroplast lipids but also from other membranes within the cells, although the
      possibility of de novo synthesis cannot be excluded. Under nitrogen-replete
      conditions, supplementation with a high concentration of CO2 promoted TAG
      production in the cells grown photoautotrophically, opening up the possibility to
      the continuous production of TAG using CO2 produced by industry. 

PMID- 24337112
TI  - Role of the Apt1 protein in polysaccharide secretion by Cryptococcus neoformans.
AB  - Flippases are key regulators of membrane asymmetry and secretory mechanisms.
      Vesicular polysaccharide secretion is essential for the pathogenic mechanisms of
      Cryptococcus neoformans. On the basis of the observations that flippases are
      required for polysaccharide secretion in plants and the putative Apt1 flippase is
      required for cryptococcal virulence, we analyzed the role of this enzyme in
      polysaccharide release by C. neoformans, using a previously characterized
      apt1Delta mutant. Mutant and wild-type (WT) cells shared important phenotypic
      characteristics, including capsule morphology and dimensions, glucuronoxylomannan
      (GXM) composition, molecular size, and serological properties. The apt1Delta
      mutant, however, produced extracellular vesicles (EVs) with a lower GXM content
      and different size distribution in comparison with those of WT cells. Our data
      also suggested a defective intracellular GXM synthesis in mutant cells, in
      addition to changes in the architecture of the Golgi apparatus. These findings
      were correlated with diminished GXM production during in vitro growth, macrophage
      infection, and lung colonization. This phenotype was associated with decreased
      survival of the mutant in the lungs of infected mice, reduced induction of
      interleukin-6 (IL-6) cytokine levels, and inefficacy in colonization of the
      brain. Taken together, our results indicate that the lack of APT1 caused defects
      in both GXM synthesis and vesicular export to the extracellular milieu by C.
      neoformans via processes that are apparently related to the pathogenic mechanisms
      used by this fungus during animal infection. 

PMID- 24337113
TI  - Myosin 1E localizes to actin polymerization sites in lamellipodia, affecting
      actin dynamics and adhesion formation.
AB  - Because the actin network in active lamellipodia is continuously assembling at
      the edge, moving inward and disassembling, there is a question as to how actin
      binding proteins and other components are transported to the leading edge and how
      nascent adhesions are stabilized. Active transport could play a significant role
      in these functions but the components involved are unknown. We show here that
      Myosin 1E (a long tailed Myosin 1 isoform) rapidly moves to the tips of active
      lamellipodia and to actin-rich early adhesions, unlike Myosin 1G, 1B or 1C (short
      tailed isoforms). Myosin 1E co-localizes with CARMIL, FHOD1, Arp3 and beta3
      integrin in those early adhesions. But these structures precede stable paxillin
      rich adhesions. Myosin 1E movement depends upon actin-binding domains and the
      presence of an SH3 oligomerization domain. Overexpression of a Myosin 1E deletion
      mutant without the extreme C-terminal interacting (SH3) domain (Myosin
      1EDeltaSH3) increases edge fluctuations and decreases stable adhesion lifetimes.
      In contrast, overexpression of Myosin 1E full tail domain (TH1+TH2+TH3/SH3)
      decreases edge fluctuation. In Myosin 1E knockdown cells, and more prominently in
      cells treated with Myosin 1 inhibitor, cell-matrix adhesions are also short-lived
      and fail to mature. We suggest that, by moving to actin polymerization sites and
      early adhesion sites in active lamellipodia, Myosin 1E might play important roles
      in transporting not only important polymerizing proteins but also proteins
      involved in adhesion stabilization. 

PMID- 24337114
TI  - Experimental evidence for UNC-6 (netrin) axon guidance by stochastic fluctuations
      of intracellular UNC-40 (DCC) outgrowth activity.
AB  - How the direction of axon guidance is determined is not understood. In
      Caenorhabditis elegans the UNC-40 (DCC) receptor mediates a response to the UNC-6
      (netrin) guidance cue that directs HSN axon development. UNC-40 becomes
      asymmetrically localized within the HSN neuron to the site of axon outgrowth.
      Here we provide experimental evidence that the direction of guidance can be
      explained by the stochastic fluctuations of UNC-40 asymmetric outgrowth activity.
      We find that the UNC-5 (UNC5) receptor and the cytoskeletal binding protein UNC
      53 (NAV2) regulate the induction of UNC-40 localization by UNC-6. If UNC-40
      localization is induced without UNC-6 by using an unc-53 mutation, the direction
      of UNC-40 localization undergoes random fluctuations. Random walk models describe
      the path made by a succession of randomly directed movement. This model was
      experimentally tested using mutations that affect Wnt/PCP signaling. These
      mutations inhibit UNC-40 localization in the anterior and posterior directions.
      As the axon forms in Wnt/PCP mutants, the direction of UNC-40 localization
      randomly fluctuates; it can localize in either the anterior, posterior, or
      ventral direction. Consistent with a biased random walk, over time the axon will
      develop ventrally in response to UNC-6, even though at a discrete time UNC-40
      localization and outgrowth can be observed anterior or posterior. Also, axon
      formation is slower in the mutants than in wild-type animals. This is also
      consistent with a random walk since this model predicts that the mean square
      displacement (msd) will increase only linearly with time, whereas the msd
      increases quadratically with time for straight-line motion. 

PMID- 24337115
TI  - Damage to the Drosophila follicle cell epithelium produces "false clones" with
      apparent polarity phenotypes.
AB  - The Drosophila follicular epithelium, which surrounds developing egg chambers, is
      a well-established model for studying epithelial polarity because it is
      continuously generated from adult stem cells, making it easy to generate
      homozygous mutant clones in a heterozygous background. Mutant clones are usually
      marked by the loss of Green Fluorescent Protein (GFP) expression, which
      distinguishes them from their green, wild-type neighbours. Here we report that
      damage to the epithelium during dissection can produce groups of GFP-negative
      cells that resemble mutant clones. Furthermore, several polarity factors, such as
      aPKC and Discs large, are not localised in these damage-induced false clones.
      This phenotype is identical to that reported for several mutants, including ampk
      and Dystroglycan mutant clones under conditions of energetic stress. Using more
      reliable systems to mark ampk and Dystroglycan null clones such as the MARCM
      system, we found that neither protein is required for epithelial polarity under
      low energy conditions. Thus, our previous report of a specific low energy
      polarity pathway is an artefact of the increased damage caused by dissecting the
      small ovaries of starved flies. However, ampk mutant cells are larger than normal
      under both starvation and well-fed conditions, indicating that AMPK restricts
      follicle cell growth even when dietary sugar is not limiting. We suspect that
      several other reports of mutants that disrupt follicle cell polarity may also be
      based on the phenotype of damage-induced false clones, and recommend the use of
      positively marked clones to avoid this potential artefact. 

PMID- 24337116
TI  - Isolation of AMP-activated protein kinase (AMPK) alleles required for neuronal
      maintenance in Drosophila melanogaster.
AB  - The maintenance of energetic homeostasis in the face of limited available
      nutrients is a complex problem faced by all organisms. One important mechanism to
      maintain energetic homeostasis involves the activation of the energy sensor AMP
      activated protein kinase (AMPK). AMPK is a cell-autonomous energy sensor that is
      highly sensitive to and regulated by the ATP to ADP and ATP to AMP ratios.
      However, the genetic analysis of AMPK signaling in vertebrates has been
      complicated by the existence of multiple redundant AMPK subunits. Here, we
      describe the identification of mutations in the single Drosophila melanogaster
      AMPK catalytic subunit (AMPKalpha) and their implications for neural maintenance
      and integrity. This article provides a citation replacement for previously
      published ampkalpha alleles, transgenes and neuronal phenotypes, which remain
      accurate; however, they were used in a previously published study that has
      subsequently been retracted (Mirouse et al., 2013). 

PMID- 24337117
TI  - Plasticity of lung development in the amphibian, Xenopus laevis.
AB  - Contrary to previous studies, we found that Xenopus laevis tadpoles raised in
      normoxic water without access to air can routinely complete metamorphosis with
      lungs that are either severely stunted and uninflated or absent altogether. This
      is the first demonstration that lung development in a tetrapod can be inhibited
      by environmental factors and that a tetrapod that relies significantly on lung
      respiration under unstressed conditions can be raised to forego this function
      without adverse effects. This study compared lung development in untreated, air
      deprived (AD) and air-restored (AR) tadpoles and frogs using whole mounts,
      histology, BrdU labeling of cell division and antibody staining of smooth muscle
      actin. We also examined the relationship of swimming and breathing behaviors to
      lung recovery in AR animals. Inhibition and recovery of lung development occurred
      at the stage of lung inflation. Lung recovery in AR tadpoles occurred at a
      predictable and rapid rate and correlated with changes in swimming and breathing
      behavior. It thus presents a new experimental model for investigating the role of
      mechanical forces in lung development. Lung recovery in AR frogs was
      unpredictable and did not correlate with behavioral changes. Its low frequency of
      occurrence could be attributed to developmental, physical and behavioral changes,
      the effects of which increase with size and age. Plasticity of lung inflation at
      tadpole stages and loss of plasticity at postmetamorphic stages offer new
      insights into the role of developmental plasticity in amphibian lung loss and
      life history evolution. 

PMID- 24337119
TI  - Par-complex aPKC and Par3 cross-talk with innate immunity NF-kappaB pathway in
      epithelial cells.

PMID- 24337118
TI  - Aberrant epidermal differentiation and disrupted DeltaNp63/Notch regulatory axis
      in Ets1 transgenic mice.
AB  - The transcription factor Ets1 is expressed at low levels in epidermal
      keratinocytes under physiological conditions, but is over-expressed in cutaneous
      squamous cell carcinoma (SCC). We previously showed that over-expression of Ets1
      in differentiated keratinocytes of the skin leads to significant pro-tumorigenic
      alterations. Here, we further extend these studies by testing the effects of over
      expressing Ets1 in the proliferative basal keratinocytes of the skin, which
      includes the putative epidermal stem cells. We show that induction of the Ets1
      transgene in the basal layer of skin during embryogenesis results in epidermal
      hyperplasia and impaired differentiation accompanied by attenuated expression of
      spinous and granular layer markers. A similar hyper-proliferative skin phenotype
      was observed when the transgene was induced in the basal layer of the skin of
      adult mice leading to hair loss and open sores. The Ets1-mediated phenotype is
      accompanied by a variety of changes in gene expression including alterations in
      Notch signaling, a crucial mediator of normal skin differentiation. Finally, we
      show that Ets1 disrupts Notch signaling in part via its ability to upregulate
      DeltaNp63, an established transcriptional repressor of several of the Notch
      receptors. Given the established tumor suppressive role for Notch signaling in
      skin tumorigenesis, the demonstrated ability of Ets1 to interfere with this
      signaling pathway may be important in mediating its pro-tumorigenic activities. 

PMID- 24337120
TI  - [Sexual and reproductive health: medical/scientific aspects].

PMID- 24337121
TI  - [Epidemiological developments of selected sexually transmitted infections in
      Germany].
AB  - The number of people living with HIV infection has been increasing since the mid
      1990s and is expected to rise further in the coming years. The HIV epidemic in
      Germany is still most affected by developments in the group of men who have sex
      with men (MSM). In this group, the number of newly diagnosed HIV infections has
      increased in recent years especially in large cities. Despite increased efforts
      to motivate HIV-infected people, who were not previously diagnosed, to be tested
      as early as possible and to seek medical treatment, the number of undiagnosed HIV
      infected persons has increased. There are more people infected with HIV than
      those who have been tested positive for HIV and subsequently receive
      antiretroviral treatment. However, early testing and treatment alone are not
      sufficient to effectively contain the infection. Increased efforts are required
      to more effectively prevent new HIV infections by combining all the available
      options. In Germany as in all other developed countries, a stronger increase in
      the number of syphilis infections among MSM is reported, which is primarily due
      to a higher willingness to risk unprotected contacts, whereby the risk of HIV
      infection is also increased. The public prevention messages available for HIV are
      only partially effective against syphilis. More frequent examinations and
      optimized therapy management are necessary in addition to the use of condoms to
      prevent the spread of syphilis, gonorrhea, and Chlamydia trachomatis. Sustainable
      containment of new HIV infections must, therefore, be accompanied by both
      containment of sexually transmitted infections (STI) and use of public prevention
      messages for HIV/STI. 

PMID- 24337122
TI  - [Deficits in STI diagnosis for men who have sex with men (MSM) in German-speaking
      cities: results of the European MSM Internet Survey (EMIS)].
AB  - BACKGROUND: Sexually transmitted infections (STIs) such as anal/genital warts,
      syphilis, and genital/rectal gonorrheal/chlamydial infections compromise the
      health of men who have sex with men (MSM), and increase the per-contact risk of
      HIV infection. Early detection of asymptomatic STIs requires regular screening
      including physical examinations and collection of clinical specimens that allow
      for the detection of infections at sites common to men's same-sex practices.
      METHODS: From June to August 2010, the European MSM Internet Survey (EMIS)
      recruited 174,209 MSM from 38 European countries to an anonymous online
      questionnaire in 25 languages. As sexual health care for MSM in most countries is
      organized locally, we chose cities for comparison. Multivariable regression
      models were used to compare accessibility of services and applied diagnostic
      procedures across 1 Dutch, 1 Swiss, 1 Austrian, 3 English, and 19 German cities
      (N = 29,962). RESULTS: The proportion of respondents tested for STIs in the last
      12 months in the absence of symptoms ranged from 13 % in Magdeburg to 48.0 % in
      Amsterdam. At a city level, low STI screening correlated with inaccessible
      services (R(2) = 0.72). At an individual level, anal/penile inspection and anal
      swabbing was most common in English cities and in Amsterdam. Compared to London,
      MSM in German-speaking cities had an adjusted odds ratio (AOR) of 0.06-0.20 for
      anal/penile inspection, and of 0.05-0.17 for anal swabbing (p < 0.001).
      CONCLUSIONS: Anal/genital warts and rectal infections are likely to be profoundly
      underdiagnosed among MSM in all German-speaking cities. This has implications for
      the sexual health of MSM, for HIV prevention, and for comparing European
      surveillance data. There is an urgent need to implement or improve sexual health
      care tailored to MSM at risk for STIs.

PMID- 24337123
TI  - [Male infertility: recent developments].
AB  - Although male reproductive functions are impaired in about half of the infertile
      couples seeking offspring, even today the examination and treatment of the male
      partner continues to be neglected. Despite the lack of evidence for a "sperm
      crisis", so highly touted in the press, the public remains worried, while the
      fact that male fertility declines beyond the age of 40 years and is accompanied
      by increasing genetic risks for the offspring goes largely unnoticed. In addition
      to a thorough physical examination supplemented by imaging techniques such as
      ultrasonography of the scrotal organs, semen analysis according to WHO
      guidelines, hormone determinations, and cyto- and molecular genetic analyses form
      part of the routine investigation of the infertile male. Few disorders have
      become subjects of rational treatment, such as hypogonadotropic hypogonadism with
      gonadotropins or GnRH, treatment of sexually transmitted diseases by antibiotics,
      and microsurgical reconstruction of blocked seminal ducts. Early treatment of
      maldescended testes in boys or changing lifestyle (e.g., discontinuation of
      smoking) are important preventive measures. In the age of evidence-based
      medicine, most empirical treatments have been demonstrated to be ineffective.
      Thus, pregnancy rates from patients with varicocele who underwent long-practiced
      surgical or radiologic interventional therapy were not different from those of
      patients receiving counseling. At present, in cases of non-obstructive
      azoospermia or severe oligoasthenoteratozoospermia, intracytoplasmic sperm
      injection (ICSI) using single sperm derived from semen or extracted from
      testicular biopsy tissue (TESE) represents the most successful treatment
      modality, although it remains symptomatic and not curative.

PMID- 24337124
TI  - [Infertility in women: latest developments].
AB  - BACKGROUND: The incidence of female infertility has not changed since the early
      1990s. Based on new data from basic research on infertility, novel options in the
      diagnostics and treatment of infertility have emerged, besides in vitro
      fertilization (IVF) and intracytoplasmic sperm injection (ICSI). AIM: This review
      summarizes the current knowledge on female infertility and on modern concepts in
      diagnostics and treatment. METHODS: A literature research on the causes of
      infertility and on treatment options was performed, including demographic
      factors, infectiology, anatomy, endocrinology and metabolism, endometriosis,
      lifestyle and environmental factors, and psychological factors. RESULTS:
      Chlamydial infection is still the major cause of tubal infertility. Improvement
      of the patient's fertility by correction of endocrine and metabolic disorders, in
      particular thyroid dysfunction and glucose metabolism, as well as fertility
      surgery are of main interest. CONCLUSIONS: Besides assisted reproductive
      techniques, concepts to optimize individual fertility have gained increasing
      importance.

PMID- 24337126
TI  - [Genetic aspects of fertility disorders].
AB  - Genetic disorders of fertility can occur at the level of gonadal differentiation
      or function, germ cell production or function, and the genital ducts. In gonadal
      dysgenesis, the differentiation of testes or ovaries is impaired. Gonadal
      dysgenesis can be caused by chromosome aberrations or monogenetic defects in XY
      or XX gonadal dysgenesis. For the biosynthesis of sexual hormones, a normal
      development of the gonads and an intact hypothalamic-pituitary-gonadal axis is
      necessary. Disorders of steroid hormone synthesis are associated with an
      increased or diminished production of sexual hormones. Clinical and genetic
      aspects of adrenogenital syndrome are discussed here. Mutations of the androgen
      receptor cause a spectrum of androgen insensitivity ranging from women with
      female external genitalia through patients with genital ambiguity to men with
      infertility. Disturbed spermatogenesis is heterogeneous and can be the result of
      chromosome aberrations such as Klinefelter syndrome or structural aberrations as
      translocations and microdeletions of the Y chromosome. Premature ovarian failure
      is characterized by amenorrhea and hypergonadotropic hypogonadism before 40 years
      of age. Beside nongenetic factors, premature ovarian failure can be caused by
      chromosome aberrations or monogenetic defects. Disorders of the genital ducts
      such as anomalies of the mullerian ducts in females and of the wolffian ducts in
      males can be associated with sterility or infertility. 

PMID- 24337125
TI  - [Natural fertility in couples and epidemiological aspects of subfertility].
AB  - BACKGROUND: In the last 40 years, fertility rates in Western societies have been
      declining as a result of lifestyle and generative behavior. AIM: This review
      summarizes current evidence-based knowledge on natural infertility and
      epidemiological aspects of subfertility. METHODS: A literature search on natural
      infertility and epidemiological aspects of subfertility was performed and the
      available data were structured and put in context. RESULTS: After six
      unsuccessful cycles, slight or potentially severe subfertility should be assumed.
      Female age, number of unsuccessful cycles, ovarian reserve, and the results of
      sperm analysis determine the reproductive potential of a subfertile couple. An
      early measurement of anti-mullerian hormone levels and a sperm analysis are
      recommended. CONCLUSIONS: Fertility awareness has gained increasing importance,
      not only in contraceptive use but also in optimizing individual fertility.

PMID- 24337127
TI  - [In vitro fertilization and intracytoplasmic sperm injection: current medical
      aspects].
AB  - Since the delivery of the first baby conceived via in vitro fertilization (IVF)
      in 1978, IVF has become a standard procedure in sterility treatment. In Germany,
      78,000 IVF/intracytoplasmic sperm injection (ICSI) cycles are performed annually
      with a delivery rate per embryo transfer of about 20 %. The cumulative delivery
      rate after three trials is more than 50 %. The main medical problems are the high
      rates of multiple pregnancies of more than 20 %, which carry an increased risk
      for mothers (preeclampsia) and children (preterm delivery, lung immaturity, brain
      problems). Also singleton babies after IVF are more often too small (small for
      gestational age, SGA) and delivered preterm. As a result, proper counselling is
      necessary. New laboratory methods have increased the success rate.
      Cryopreservation techniques such as vitrification are standard for freezing
      oocytes, pronuclear-stage oocytes and embryos if they are not needed during the
      current treatment cycle. Continuous observation of embryos by time-lapse imaging
      helps to identify the best embryos for transfer. The current legislation in the
      German embryo protection act (Embryonenschutzgesetz) is the main problem. It is
      unclear how many fertilized oocytes can be cultured to achieve a transfer of one
      to three embryos. The prohibition of oocyte donation and surrogacy are not
      comprehensible from a medical, psychological, and ethical point of view.
      Reimbursement of publicly insured patients is restricted in comparison with other
      European countries. Married couples receive half of the payment for three
      IVF/ICSI cycles; non-married couples receive no payment at all.

PMID- 24337128
TI  - [Prenatal diagnostics: current medical aspects].
AB  - During the last few years, there has been a rapid development in prenatal
      diagnosis. Due to the improvements in sonographic examinations and the
      introduction of first-trimester screening, the number of invasive prenatal
      diagnostic procedures has dropped by more than 50 %. Recently, noninvasive
      prenatal diagnostic tests with cell-free fetal DNA from maternal blood have also
      become available and will further enhance this development. As invasive prenatal
      procedures will become less frequent in the near future, the proportion of
      procedure-related abortions will further decrease.

PMID- 24337129
TI  - [Preimplantation diagnosis--PID: preimplantation genetic diagnosis (PGD) and
      preimplantation genetic screening (PGS)].
AB  - Preimplantation diagnosis (PID) comprises all the relevant diagnostic procedures
      for the investigation of genetic, structural, or numerical changes of the genetic
      information in spermatozoa and oocytes as well as in embryos after in vitro
      fertilization (IVF) or intracytoplasmic sperm injection (ICSI). PID of oocytes is
      well established in Germany for the above-mentioned indications. PID at the
      embryonic level, i.e., trophectoderm biopsy of blastocysts, is possible in
      centers with proven expertise in reproductive medicine and human genetics. A high
      risk for genetic disease in the child or a high likelihood for stillbirth or
      miscarriage is a prerequisite for PID. A specialized ethics committee is required
      to look into each case before making a decision. While PID is still under
      development in Germany, it has been a well-established technology worldwide for
      24 years. International experience in PID and the resulting implications are
      discussed in this article. 

PMID- 24337130
TI  - [Prenatal care in Germany].
AB  - Prenatal care in Germany is based on a nationwide standardized program of care
      for pregnant women. Besides support and health counseling, it comprises
      prevention or early detection of diseases or unfavorable circumstances with risks
      for mother and child. Prenatal care is regulated by law and structured by
      directives and standard procedures in maternity guidelines (Mutterschafts
      Richtlinien). This includes information and counseling of future mothers on
      offers of psychosocial and medical assistance in normal pregnancies as well as in
      unplanned or unwanted pregnancies. Further aspects are clinical examinations and
      risk determinations for genetic variations or direct genetic analysis. During
      pregnancy, medical history, clinical examination, and blood testing are part of
      the sophisticated program, which includes at least three standardized sonographic
      examinations at 10, 20, and 30 weeks of gestation. The maternity passport allows
      a pregnant woman to carry the most relevant information on her pregnancy and her
      personal risks with her. For 45 years now, women in Germany are used to carrying
      their Mutterpass. Societal changes have influenced the central goals of maternity
      care: In the beginning, the mortality of mother and child had to be reduced.
      Today, maternal morbidity and impaired development of the child are the center of
      interest, with expansion to familial satisfaction. The reduction in the mortality
      and morbidity of both the mother and the child during pregnancy, delivery, and
      postpartum can be attributed to prenatal care. Thus, investment in a program of
      nationwide structured prenatal care seems to be worthwhile-despite the lack of
      evidence concerning its effectiveness. 

PMID- 24337131
TI  - [Intersex and differences of sex development: background, diagnostics, and
      concepts of care].
AB  - Intersex is an inherited incongruence of chromosomal, gonadal, and genital sexual
      characteristics. A typical clinical situation of intersex is the ambiguous
      genitalia in the newborn. Diagnostics, counseling, and therapy should be offered
      by specialized multidisciplinary health-care teams. The focus is not only on
      medical issues but also on psychological, social, and ethical aspects. In the
      international literature, intersex is now termed "disorders of sex development"
      (DSD). Alternatively, some authors use "differences of sex development" to
      underline that patients do not necessarily feel they have a "disorder" but rather
      a "difference" of sex development compared with normal sex development. 

PMID- 24337133
TI  - The antioxidant activity of soursop decreases the expression of a member of the
      NADPH oxidase family.
AB  - Cellular oxidative stress produced by an increase in free radicals is one of the
      factors that promote the development of chronic degenerative diseases; therefore,
      consuming natural antioxidants helps minimize their negative effects. This study
      evaluated the cytotoxicity of the soursop extract (Annona muricata), its
      cytoprotective capacity against oxidative stress induced by hydrogen peroxide,
      the inhibitory potential of reactive oxygen species (ROS), the molecular
      mechanism of its antioxidant action, and its capacity to repair cellular damage
      in the fibroblast cell line. The soursop extract proved not to be cytotoxic in
      fibroblast cultures and showed cytoprotective capacity against hydrogen peroxide
      induced stress; in cell culture it reduced the generation of ROS significantly by
      inhibiting a sub-unit of the NADPH oxidase enzyme (p47phox). The soursop extract
      can prevent damage caused by cellular oxidants. 

PMID- 24337132
TI  - Health-related quality of life in epidermolysis bullosa: Validation of the Dutch
      QOLEB questionnaire and assessment in the Dutch population.
AB  - Defining the health-related quality of life (HRQoL) in patients suffering from
      the heritable blistering disease epidermolysis bullosa (EB) is important in
      assessing the efficacy of new treatments. The quality of life in EB questionnaire
      (QOLEB) is an English 17-item EB-specific HRQoL measurement tool. The aim of this
      study was to develop a validated and reliable QOLEB in Dutch and assess the HRQoL
      in Dutch EB patients. The QOLEB was translated to Dutch according to protocol.
      Fifty-five adult patients across 4 EB subtypes participated. The QOLEB had
      excellant correlation with the Skindex-29 (rhos = 0.86), good correlation with
      the SF-36 physical score (rhos = -0.75), and moderate correlation with the SF-36
      mental score (rhos = -0.43). The discriminative validity between the 4 different
      EB subtypes was significant (p = 0.002). The internal consistency was excellent
      (alpha = 0.905), and the test-retest reliability strong (rhos = 0.88). In
      conclusion, the Dutch QOLEB is a reliable and valid instrument for the assessment
      of the HRQoL in adult EB patients.

PMID- 24337134
TI  - Metabolic profiling of amino acids in cellular samples via zwitterionic sub-2 MUm
      particle size HILIC-MS/MS and a uniformly 13C labeled internal standard.
AB  - A novel analytical method using hydrophilic interaction liquid chromatography
      combined with electrospray tandem mass spectrometry for metabolic profiling of
      free, underivatized amino acids is presented. The separation uses a zwitterionic
      modified silica-based stationary phase with 1.8-MUm particle size functionalized
      with ammonium sulfonic acid groups. Quantification is based on external standard
      calibration using a Pichia pastoris cell extract grown on uniformly (13)C labeled
      glucose as an internal standard. The absolute limits of detection in the cellular
      matrix were in the subpicomolar range. Measurement accuracy was assessed by
      analyzing NIST Standard Reference Material 2389a, which provides certified values
      for 17 amino acids. The recovery of the amino acids ranged between 65 % (proline)
      and 120 % (lysine), with excellent repeatability precision below 2.5 % (n = 5).
      Only, cystine showed poor recovery (29 %) and repeatability precision (13 %).
      Generally, the long-term precision obtained by hydrophilic interaction liquid
      chromatography-tandem mass spectrometry was excellent, being on average less than
      9 % over 20 h of measurement time. Moreover, the novel separation method had
      average repeatability and reproducibility of the chromatographic peak width over
      time periods of 20 h and 6 months of 8 and 15 %, respectively, demonstrating its
      high robustness in routine analysis of cellular samples. Large concentration
      differences depending on the amino acid were found in the cell extracts,
      typically ranging from 0.002 nmol per milligram of cell dry weight (cystine) to
      56 nmol per milligram of cell dry weight (arginine and glutamic acid). 

PMID- 24337135
TI  - Hollow-fiber flow field-flow fractionation with multi-angle laser scattering
      detection for aggregation studies of therapeutic proteins.
AB  - The rapid development of protein-based pharmaceuticals highlights the need for
      robust analytical methods to ensure their quality and stability. Among proteins
      used in pharmaceutical applications, an important and ever increasing role is
      represented by monoclonal antibodies and large proteins, which are often modified
      to enhance their activity or stability when used as drugs. The bioactivity and
      the stability of those proteins are closely related to the maintenance of their
      complex structure, which however are influenced by many external factors that can
      cause degradation and/or aggregation. The presence of aggregates in these drugs
      could reduce their bioactivity and bioavailability, and induce immunogenicity.
      The choice of the proper analytical method for the analysis of aggregates is
      fundamental to understand their (size) dimensional range, their amount, and if
      they are present in the sample as generated by an aggregation or as an artifact
      due to the method itself. Size exclusion chromatography is one of the most
      important techniques for the quality control of pharmaceutical proteins; however,
      its application is limited to relatively low molar mass aggregates. Among the
      techniques for the size characterization of proteins, field-flow fractionation
      (FFF) represents a competitive choice because of its soft mechanism due to the
      absence of a stationary phase and application in a broader size range, from
      nanometer- to micrometer-sized analytes. In this paper, the microcolumn variant
      of FFF, the hollow-fiber flow FFF, was online coupled with multi-angle light
      scattering, and a method for the characterization of aggregates with high
      reproducibility and low limit of detection was demonstrated employing an avidin
      derivate as sample model. 

PMID- 24337136
TI  - Rapid colorimetric detection of Salmonella typhimuriumusing a selective
      filtration technique combined with antibody-magnetic nanoparticle nanocomposites.
AB  - Detection of pathogenic bacteria that pose a great risk to human health requires
      a rapid, convenient, reliable, and sensitive detection method. In this study, we
      developed a selective filtration method using monoclonal antibody (MAb)-magnetic
      nanoparticle (MNP) nanocomposites for the rapid and sensitive colorimetric
      detection of Salmonella typhimurium. The method contains two key steps: the
      immunomagnetic separation of the bacteria using MAb-MNP nanocomposites and the
      filtration of the nanocomposite-bound bacteria. Color signals from the
      nanocomposites remaining on the membrane were measured, which reflected the
      amount of bacteria in test samples. Immunomagnetic capture efficiencies of 8 to
      90 % for various concentrations of the pathogen (2 * 10(4)-2 * 10(1) cells) were
      obtained. After optimization of the method, 2 * 10(1) cells of S. typhimurium in
      pure culture solution was detectable as well as in artificially inoculated
      vegetables (100 cells/g). The method was confirmed to be highly specific to S.
      typhimurium without cross-reaction to other pathogenic bacteria and could be
      concluded within 45 min, yielding results in a shorter or similar time period as
      compared with recently reported antibody immobilized on magnetic-particle-based
      methods. This study also demonstrated direct application of MAb-MNP
      nanocomposites without a dissociation step of bacteria from magnetic beads in
      colorimetric assays in practice. 

PMID- 24337137
TI  - Development and validation of a LC-MS/MS method for D-cycloserine determination
      in human plasma for bioequivalence study.
AB  - A reliable and high throughput high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) method was developed and validated for determining
      levels of the antitubercular drug-D -cycloserine in human plasma. Plasma samples
      analyte with an internal standard (IS) (niacin) were prepared by solid-phase
      extraction using Waters Oasis MCX cartridges. The chromatographic separation was
      performed using the HILIC mode on a YMC-Pack SIL-06 column (150 * 4.6 mm; 3 MUm)
      under isocratic conditions. The run time of analysis was 5 min. The mobile phase
      consisted of methanol, propanol-2 and 0.075 % trifluoroacetic acid (66.5:28.5:5,
      v/v/v). Protonated ions formed by turbo ion spray in positive mode were used to
      detect the analyte and the IS. MS/MS detection was used to monitor the
      fragmentation of 103-75 m/z for cycloserine and 124 to 80 m/z for niacin (IS) on
      an API 4000 (AB Sciex) triple quadrupole mass spectrometer. A linear dynamic
      range of 0.3-30 MUg/mL was established for cycloserine using 0.2 mL human plasma
      and a 1 MUL injection volume. The mean relative recovery of cycloserine and
      niacin were 77.2 and 82.4 %, respectively. The procedure of sample preparation
      was consistent and reproducible (precision, 0.8-3.4 %; accuracy, 93.8-104.9 %).
      The method was validated in accordance with requirements of the European
      Medicines Agency and successfully applied to a bioequivalence study of 250 mg
      tablet formulations in 23 healthy human subjects. 

PMID- 24337138
TI  - Kinetics of chemically mediated neurodegeneration/neuroregeneration of mouse
      olfactory epithelium: monitoring by hyperlayer sedimentation field flow
      fractionation.
AB  - The increase in the incidence of neurodegenerative diseases linked to aging or
      injury needs to be addressed in research into neuroprotective or
      neuroregenerative therapies, and requires the development of specific biological
      models. To achieve this goal we propose (1) the use of the mouse olfactory
      epithelium as a biological support which specifically exhibits a regenerative or
      a self-renewing capacity and during the lifetime necessitates the presence of
      neural stem cells, and (2) the use of an intraperitoneal injection of 2,6
      dichlorobenzonitrile (diclobenil) as a chemical inducer of neurodegeneration in
      olfactory epithelium by selectively killing mature cells. We developed a
      biological model to follow the processes of neurodegeneration (chemically
      induced) and neuroregeneration (self-renewal of olfactory epithelium). The
      purpose of this study was to develop a method to monitor quickly
      neurodegeneration/neuroregeneration processes in order to further screen
      protective and regenerative therapies. For this purpose, we used the
      sedimentation field flow fractionation elution of olfactory epithelium. We
      obtained specific elution profiles and retention parameters allowing the
      monitoring of the induction and kinetics of biological processes. The use of
      insulin-like growth factor 1alpha as a neuroprotective agent in an innovative
      nebulization protocol showed sedimentation field flow fractionation to be a
      simple, fast and low-cost method to monitor such a biological event on the scale
      of an entire organism. 

PMID- 24337139
TI  - A solid-phase fluorescent biosensor for the determination of phenolic compounds
      and peroxides in samples with complex matrices.
AB  - A solid-phase fluorescent biosensor for the determination of phenolic compounds
      (simple substituted phenols and catecholamines) and peroxides has been developed.
      The biosensor has a simple construction and the analytical signal is measured
      directly in a biosensitive layer {peroxidase-chitosan} on the sensor surface.
      This approach allowed analyzing samples with complex matrices (including water
      insoluble samples and nontransparent solutions) without their preliminary
      pretreatment. Two novel fluorescent indicator reactions for the determination of
      the above-mentioned analytes in wide concentration ranges (from nmol l(-1) to mm
      l(-1)) which provided an analytical signal registration on a solid phase were
      proposed. The developed sensor was applied successfully for the analysis of
      urine, cosmetics, pharmaceuticals preparations, etc. 

PMID- 24337140
TI  - The preventable burden of productivity loss due to suboptimal asthma control: a
      population-based study.
AB  - BACKGROUND: Productivity loss is an overlooked aspect of the burden of chronic
      health conditions. While modern guidelines emphasize achieving clinical control
      in asthma management, few studies have reported on the relationship between
      asthma control and productivity loss. We calculated the productivity loss that
      can be avoided by achieving and maintaining clinical control in employed adults
      with asthma. METHODS: We prospectively recruited a population-based random sample
      of adults with asthma in British Columbia, Canada. We measured productivity loss
      due to absenteeism and presenteeism using validated instruments, and ascertained
      asthma control according to the GINA (Global Initiative for Asthma)
      classification. We estimated the average gain in productivity for each individual
      if the individual's asthma was controlled in the past week, by fitting two-part
      regression models associating asthma control and productivity loss, controlling
      for potential confounding variables. RESULTS: The final sample included 300
      employed adults (mean age, 47.9 years [SD 12.0]; 67.3% women). Of these, 49
      (16.3%) reported absenteeism, and 137 (45.7%) reported presenteeism. Productivity
      loss due to presenteeism, but not absenteeism, was associated with asthma
      control. A person with uncontrolled asthma would avoid $184.80 (Canadian dollars
      [CAD]) in productivity loss by achieving clinical control during a week,
      CAD$167.50 (90.6%) of which would be due to presenteeism. The corresponding value
      was CAD$34.20 for partially controlled asthma and was not statistically
      significant. CONCLUSIONS: Our results indicate that substantial gain in
      productivity can be obtained by achieving asthma control. Presenteeism is more
      responsive than absenteeism to asthma control, and, thus, is a more important
      source of preventable burden.

PMID- 24337141
TI  - The small GTPase RhoA regulates the expression and function of the sodium channel
      Nav1.5 in breast cancer cells.
AB  - Voltage-gated Na+ channels (VGSCs) are highly expressed in several types of
      carcinomas including breast, prostate and lung cancers as well as in mesothelioma
      and cervical cancers. Although the VGSCs activity is considered crucial for the
      potentiation of cancer cell migration and invasion, the mechanisms responsible
      for their functional expression and regulation in cancer cells remain unclear. In
      the present study, the role of the small GTPase RhoA in the regulation of
      expression and function of the Nav1.5 channel in the breast cancer cell lines MDA
      MB 231 and MCF-7 was investigated. RhoA silencing significantly reduced both
      Nav1.5 channel expression and sodium current indicating that RhoA exerts a
      stimulatory effect on the synthesis of an active form of Nav1.5 channel in cancer
      cells. The inhibition of Nav1.5 expression dramatically reduced both cell
      invasion and proliferation. In addition, a decrease of RhoA protein levels
      induced by Nav1.5 silencing was observed. Altogether, these findings revealed: i)
      the key role of the small GTPase RhoA in upregulation of Nav1.5 channel
      expression and tumor aggressiveness, and ii) the existence of a positive feedback
      of Nav1.5 channels on RhoA protein levels.

PMID- 24337143
TI  - Model of soft tissue artifact propagation to joint angles in human movement
      analysis.
AB  - This work describes the kinematic laws that govern the transmission of soft
      tissue artifact errors to kinematic variables in the analysis of human movements.
      Artifacts are described as relative translations and rotations of the marker
      cluster over the bone, and a set of explicit expressions is defined to account
      for the effect of that relative motion on different representations of rotations:
      the rotation around the screw axis, or rotation vector, and three Euler angle
      sequences (XY'Z, YX'Y", ZX'Y"). Although the error transmission is nonlinear in
      all cases, the effect of artifacts is greater on Euler sequences than on the
      rotation vector. Specifically, there are crosstalk effects in Euler sequences
      that amplify the errors near singular configurations. This fact is an additional
      source of variability in studies that describe artifacts by comparing the Euler
      angles obtained from skin markers, with the angles of an artifact-free gold
      standard. The transmission of errors to rotation vector coordinates is less
      variable or dependent on the type of motion. This model has been tested in an
      experiment with a deformable mechanical model with a spherical joint. 

PMID- 24337144
TI  - Thromboresistance comparison of the HeartMate II ventricular assist device with
      the device thrombogenicity emulation- optimized HeartAssist 5 VAD.
AB  - Approximately 7.5 * 106 patients in the US currently suffer from end-stage heart
      failure. The FDA has recently approved the designations of the Thoratec HeartMate
      II ventricular assist device (VAD) for both bridge-to-transplant and destination
      therapy (DT) due to its mechanical durability and improved hemodynamics. However,
      incidence of pump thrombosis and thromboembolic events remains high, and the life
      long complex pharmacological regimens are mandatory in its VAD recipients. We
      have previously successfully applied our device thrombogenicity emulation (DTE)
      methodology for optimizing device thromboresistance to the Micromed Debakey VAD,
      and demonstrated that optimizing device features implicated in exposing blood to
      elevated shear stresses and exposure times significantly reduces shear-induced
      platelet activation and significantly improves the device thromboresistance. In
      the present study, we compared the thrombogenicity of the FDA-approved HeartMate
      II VAD with the DTE-optimized Debakey VAD (now labeled HeartAssist 5). With
      quantitative probability density functions of the stress accumulation along large
      number of platelet trajectories within each device which were extracted from
      numerical flow simulations in each device, and through measurements of platelet
      activation rates in recirculation flow loops, we specifically show that: (a)
      Platelets flowing through the HeartAssist 5 are exposed to significantly lower
      stress accumulation that lead to platelet activation than the HeartMate II,
      especially at the impeller-shroud gap regions (b) Thrombus formation patterns
      observed in the HeartMate II are absent in the HeartAssist 5 (c) Platelet
      activation rates (PAR) measured in vitro with the VADs mounted in recirculation
      flow-loops show a 2.5-fold significantly higher PAR value for the HeartMate II.
      This head to head thrombogenic performance comparative study of the two VADs, one
      optimized with the DTE methodology and one FDA-approved, demonstrates the
      efficacy of the DTE methodology for drastically reducing the device thrombogenic
      potential, validating the need for a robust in silico/in vitro optimization
      methodology for improving cardiovascular devices thromboresistance.

PMID- 24337145
TI  - Mutational analysis of the BRCA2 gene in breast carcinoma patients of Kashmiri
      descent.
AB  - Breast cancer demonstrates geographical and ethnic variation in its incidence
      reflecting the effect of local environmental conditions and lifestyle. The
      genesis of the disease has further been complexed by the involvement of a number
      of genes with small effects and above all by population heterogeneity.
      Accordingly, variations in genes, including breast cancer 1, early onset
      (BRCA1)/breast cancer 2, early onset (BRCA2), that have been markedly associated
      with the breast cancer phenotype exhibit a scattered mutational pattern in
      different populations. The present study was aimed to analyze the sequence
      variations in BRCA2 gene in a case control manner in ethnically pure Kashmiri
      population using PCR. Sequencing of BRCA2 exons revealed the presence of five
      sequence variations, four of which present in exon 11 alone were somatic and one
      was germline located in the U-terminal region (UTR) of exon 2. Out of these, the
      two somatic mutations comprised of substitutions, one representing a missense
      mutation leading to an amino-acid substitution at codon 991 and the other was a
      silent mutation at codon 1131, whereas the other two mutations located in exon 11
      represented a loss of polymorphism. Codons for amino acid position 846 and 868
      were demonstrated to be heterozygous polymorphic variants in 66% of the normal
      breast tissue samples, whereas the heterozygous polymorphic variant codons at the
      two loci were replaced by a homozygous genotype in associated tumor tissue in 88%
      of cases. These two mutations were always linked. Germline variation observed in
      exon 2 was located in the UTR region at contig position 13870572 (rs1799943).
      Other screened exons of BRCA2 did not demonstrate any sequence variation. These
      variations may contribute to breast cancer susceptibility along with variations
      in other low penetrating genes in sporadic types of breast cancer in this cohort
      of the population.

PMID- 24337147
TI  - Does respiration influence breast volumetric change measurement with the three
      dimensional scanning technique?
AB  - BACKGROUND: Measurement of volumetric change after aesthetic and reconstructive
      breast surgery is of great significance to plastic surgeons. This study aimed to
      investigate the influence of respiration on measurement of breast volumetric
      change via a three-dimensional (3D) scanning technique. METHODS: In this study,
      ten augmentation mammaplasty patients received preoperative 3D scanning in
      different respiration states at three time points: the end of normal exhalation
      (ENE1), the end of normal inhalation (ENI), and the end of normal exhalation
      again (ENE2). Using Geomagic Studio 12 software, breast volumetric change error
      (BVCE) was measured between the ENE1 scan and the ENI scan (R1) and between the
      ENE1 scan and ENE2 scan (R2). Three-dimensional deviation, defined as the
      shortest distance from one scan to any point on the other scan, was measured in
      R1 and R2. A paired-sample t test was used to compare the means of BVCE and the
      3D deviation between R1 and R2. Pearson's correlation coefficient was calculated
      between 3D deviation and BVCE. For the analysis, SPSS program version 16 was
      used. Differences were considered statistically significant at P values lower
      than 0.05. RESULTS: The mean breast volume was 352.3 +/- 52.7 ml, and BVCE was
      significantly lower in R1 than in R2 (9.7 vs. 21.3 ml; P = 0.000). The 3D
      deviation was significantly higher in R2 than in R1 (1.600 vs. 0.887; P = 0.000).
      In the analysis, BVCE was not correlated significantly with 3D deviation in R1 (P
      = 0.157) but was significantly correlated with 3D deviation in R2 (correlation
      coefficient = 0.766; P = 0.000). CONCLUSIONS: Keeping patients in the same
      respiration state is crucial for accurate measurement of breast volumetric change
      via the 3D scanning technique. LEVEL OF EVIDENCE I: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 24337146
TI  - Role of house flies in the ecology of Enterococcus faecalis from wastewater
      treatment facilities.
AB  - Enterococci are important nosocomial pathogens, with Enterococcus faecalis most
      commonly responsible for human infections. In this study, we used several
      measures to test the hypothesis that house flies, Musca domestica (L.), acquire
      and disseminate antibiotic-resistant and potentially virulent E. faecalis from
      wastewater treatment facilities (WWTF) to the surrounding urban environment.
      House flies and sludge from four WWTF (1-4) as well as house flies from three
      urban sites close to WWTF-1 were collected and cultured for enterococci.
      Enterococci were identified, quantified, screened for antibiotic resistance and
      virulence traits, and assessed for clonality. Of the 11 antibiotics tested, E.
      faecalis was most commonly resistant to tetracycline, doxycycline, streptomycin,
      gentamicin, and erythromycin, and these traits were intra-species horizontally
      transferrable by in vitro conjugation. Profiles of E. faecalis (prevalence,
      antibiotic resistance, and virulence traits) from each of WWTF sludge and
      associated house flies were similar, indicating that flies successfully acquired
      these bacteria from this substrate. The greatest number of E. faecalis with
      antibiotic resistance and virulence factors (i.e., gelatinase, cytolysin,
      enterococcus surface protein, and aggregation substance) originated from WWTF-1
      that processed meat waste from a nearby commercial meat-processing plant,
      suggesting an agricultural rather than human clinical source of these isolates.
      E. faecalis from house flies collected from three sites 0.7-1.5 km away from WWTF
      1 were also similar in their antibiotic resistance profiles; however, antibiotic
      resistance was significantly less frequent. Clonal diversity assessment using
      pulsed-field gel electrophoresis revealed the same clones of E. faecalis from
      sludge and house flies from WWTF-1 but not from the three urban sites close to
      WWTF-1. This study demonstrates that house flies acquire antibiotic-resistant
      enterococci from WWTF and potentially disseminate them to the surrounding
      environment.

PMID- 24337148
TI  - Accuracy of computational soft tissue predictions in orthognathic surgery from
      three-dimensional photographs 6 months after completion of surgery: a preliminary
      study of 13 patients.
AB  - BACKGROUND: This study aimed at a preliminary evaluation of the accuracy of
      computed three-dimensional (3D) predictions in orthognathic surgery by comparing
      predicted and real postoperative results. METHODS: Pre- and postoperative 3D
      photographs and time-matching computed tomography (CT) and cone-beam CT scans of
      the face of 13 patients with dentofacial deformities were analyzed. Three
      dimensional photographs were fused with preoperative CT data using dedicated
      software (3dMDvultus, version 2.2.0.8). Postoperative CT data were superposed on
      the preoperative skull. With an activated rendering function, the osteotomies
      were simulated in the preoperative CT data and the bony segments moved to their
      real postoperative position, resulting in a textured soft tissue prediction. This
      computed skin surface was compared with the real postoperative result by dividing
      the face into a surgically treated lower half and an untreated upper half. A
      statistical quantitative analysis of the surfaces was performed. RESULTS: The
      mean differences between surfaces were +0.27 mm for the untreated upper half and 
      0.64 mm for the surgically treated lower half (p < 0.001). Averaged distributions
      of absolute errors showed more discrepancies between predicted and real
      postoperative results in the lower half of the face. Errors exceeding 3 mm were
      encountered in 4 % of the upper halves versus 29.8 % of the lower halves (p <
      0.001). CONCLUSIONS: The accuracy of a specific software platform for predicting
      3D soft tissue changes after surgery was insufficient. LEVEL OF EVIDENCE IV: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24337149
TI  - Co2/Erbium:YAG/Dye laser combination: an effective and successful treatment for
      angiofibromas in tuberous sclerosis.
AB  - BACKGROUND: Tuberous sclerosis, an autosomal dominant neurocutaneous syndrome
      seen in approximately 1 in 6,000 people worldwide, is characterized by the
      appearance of hamartomas in multiple organs. The classic clinical triad consists
      of angiofibromas, epilepsy, and developmental delay. Dermatologic disorder is one
      of the main characteristics. Angiofibromas, a common form of presentation, causes
      significant cosmetic and medical problems. The current treatment for skin lesions
      is laser therapy. The carbon dioxide (CO2) laser has been used satisfactorily in
      treating these lesions, but several studies have demonstrated a high percentage
      of recurrences. Erbium:yttrium-aluminum-garnet (YAG) laser treatment has been
      used to resurface skin abnormalities in patients with dermatologic conditions.
      The dye laser as an alternative uses the principles of selective photothermolysis
      and is very effective in treating the vascular component of tuberous sclerosis.
      The use of all these lasers to treat skin lesions in patients affected by
      tuberous sclerosis has never been described in the literature. METHODS: A
      retrospective study, conducted from 2007 to May 2013, investigated 13 patients
      who had tuberous sclerosis treated with an erbium:YAG/CO2/dye laser combination.
      RESULTS: All the patients showed great improvement of their skin lesions. The
      results were evident immediately after the first treatment. No patient
      experienced complications or recurrence. CONCLUSIONS: The combined use of the
      erbium:YAG/Dye/CO2 laser is a safe and effective treatment for skin lesions in
      patients affected by tuberous sclerosis. LEVEL OF EVIDENCE V: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24337150
TI  - [DRESS syndrome following sulfasalazine treatment].
AB  - A female patient developed systemic rash, lung edema, electrocardiogram (ECG)
      abnormalities and fulminant hepatitis with partial liver failure 4 weeks after
      the start of sulfasalazine treatment. Peripheral T-cell activation, a positive
      PCR test for human herpesvirus (HHV) 6 as well as eosinophilia in bronchial
      lavage and a differential blood count were also present. After initiation of
      systemic corticosteroid therapy and cessation of accompanying medication the
      clinical symptoms and abnormal laboratory test levels were gradually resolved. A
      DRESS syndrome (drug rash with eosinophilia and systemic symptoms) was confirmed
      in accordance with the diagnostic criteria. 

PMID- 24337152
TI  - [Colorectal liver metastasis: More chemotherapy, more surgery?].

PMID- 24337151
TI  - Surgical planning and manual image fusion based on 3D model facilitate
      laparoscopic partial nephrectomy for intrarenal tumors.
AB  - PURPOSE: Construction of three-dimensional (3D) model of renal tumor facilitated
      surgical planning and imaging guidance of manual image fusion in laparoscopic
      partial nephrectomy (LPN) for intrarenal tumors. MATERIALS AND METHODS: Fifteen
      patients with intrarenal tumors underwent LPN between January and December 2012.
      Computed tomography-based reconstruction of the 3D models of renal tumors was
      performed using Mimics 12.1 software. Surgical planning was performed through
      morphometry and multi-angle visual views of the tumor model. Two-step manual
      image fusion superimposed 3D model images onto 2D laparoscopic images. The image
      fusion was verified by intraoperative ultrasound. Imaging-guided laparoscopic
      hilar clamping and tumor excision was performed. Manual fusion time, patient
      demographics, surgical details, and postoperative treatment parameters were
      analyzed. RESULTS: The reconstructed 3D tumor models accurately represented the
      patient's physiological anatomical landmarks. The surgical planning markers were
      marked successfully. Manual image fusion was flexible and feasible with fusion
      time of 6 min (5-7 min). All surgeries were completed laparoscopically. The
      median tumor excision time was 5.4 min (3.5-10 min), whereas the median warm
      ischemia time was 25.5 min (16-32 min). Twelve patients (80 %) demonstrated renal
      cell carcinoma on final pathology, and all surgical margins were negative. No
      tumor recurrence was detected after a media follow-up of 1 year (3-15 months).
      CONCLUSIONS: The surgical planning and two-step manual image fusion based on 3D
      model of renal tumor facilitated visible-imaging-guided tumor resection with
      negative margin in LPN for intrarenal tumor. It is promising and moves us one
      step closer to imaging-guided surgery.

PMID- 24337153
TI  - [Neoadjuvant chemotherapy or primary surgery for colorectal liver metastases. Pro
      primary surgery].
AB  - Approximately 50 % of patients with colorectal cancer (CRC) develop liver
      metastases, with the liver being the only site of metastasis in the majority of
      patients. Liver resection is the standard treatment of CRC liver metastases as it
      achieves a 5-year survival of 36-51 %. The primary goal in the treatment of non
      resectable liver metastases is to achieve resectability by preoperative
      chemotherapy as even secondary liver resection after down-sizing is associated
      with improved overall survival. Furthermore, resectability can be increased by
      two-stage surgical procedures; however, the assessment of resectability varies
      widely even among experts in the field. In cases of suspected non-resectability
      patients should therefore be liberally admitted for a second opinion to centers
      of liver surgery. Perioperative chemotherapy in primarily resectable cases has
      only demonstrated an improvement in recurrence-free survival in subgroup
      analyses. Moreover, modern potent chemotherapy regimens increase the surgical
      morbidity depending on the duration of treatment: the lower the histological
      response of the metastases and the more treatment cycles are applied, the higher
      is the parenchymal damage with related surgical morbidity. Therefore,
      perioperative chemotherapy of resectable liver metastases should be viewed with
      caution and should not be considered the standard of care. 

PMID- 24337155
TI  - Circulating levels of perfluoroalkyl substances and prevalent diabetes in the
      elderly.
AB  - AIMS/HYPOTHESIS: Several environmental contaminants, such as polychlorinated
      biphenyls, dioxins, bisphenol A and phthalates, have been linked to diabetes. We
      therefore investigated whether other kinds of contaminants, perfluoroalkyl
      substances (PFAS), also called perfluorinated compounds (PFCs), are also
      associated with diabetes. METHODS: The Prospective Investigation of the
      Vasculature in Uppsala Seniors (PIVUS) study investigated 1,016 men and women
      aged 70 years. Seven PFAS were detected in almost all participant sera by ultra
      high performance liquid chromatograph/tandem mass spectrometry. Diabetes was
      defined as use of hypoglycaemic agents or fasting glucose >7.0 mmol/l. RESULTS:
      114 people had diabetes. In the linear analysis, no significant relationships
      were seen between the seven PFAS and prevalent diabetes. However, inclusion of
      the quadratic terms of the PFAS revealed a significant non-linear relationship
      between perfluorononanoic acid (PFNA) and diabetes, even after adjusting for
      multiple confounders (OR 1.96, 95% CI 1.19, 3.22, p = 0.008 for the linear term
      and OR 1.25, 95% CI 1.08, 1.44, p = 0.002 for the quadratic term).
      Perfluorooctanoic acid (PFOA) also showed such a relationship (p = 0.01). PFOA
      was related to the proinsulin/insulin ratio (a marker of insulin secretion), but
      none of the PFAS was related to the HOMA-IR (a marker of insulin resistance)
      following adjustment for multiple confounders. CONCLUSIONS/INTERPRETATION: PFNA
      was related to prevalent diabetes in a non-monotonic fashion in this cross
      sectional study, supporting the view that this perfluoroalkyl substance might
      influence glucose metabolism in humans at the level of exposure seen in the
      general elderly population.

PMID- 24337154
TI  - A sustained increase in plasma NEFA upregulates the Toll-like receptor network in
      human muscle.
AB  - AIMS/HYPOTHESIS: Insulin-sensitive tissues (muscle, liver) of individuals with
      obesity and type 2 diabetes mellitus are in a state of low-grade inflammation,
      characterised by increased Toll-like receptor (TLR) expression and TLR-driven
      signalling. However, the cause of this mild inflammatory state is unclear. We
      tested the hypothesis that a prolonged mild increase in plasma NEFA will increase
      TLR expression and TLR-driven signalling (nuclear factor kappaB [NFkappaB] and
      mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean
      healthy individuals. METHODS: Twelve lean, normal-glucose-tolerant participants
      were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid
      followed by a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis muscle
      biopsies were performed before and during the clamp. RESULTS: Lipid infusion
      impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral
      insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased
      expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and
      inhibitor of kappaB kinase-NFkappaB (CHUK [IKKA], c-REL [REL] and p65 [RELA,
      NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased
      extracellular signal-regulated kinase (ERK) phosphorylation (p < 0.05) and tended
      to reduce the content of inhibitor of kappa Balpha (p = 0.09). The muscle content
      of most diacylglycerol, ceramide and acylcarnitine species was unaffected. In
      summary, insulin resistance induced by prolonged low-dose lipid infusion occurs
      together with increased TLR-driven inflammatory signalling and impaired insulin
      stimulated IRS-1 tyrosine phosphorylation. CONCLUSIONS/INTERPRETATION: A
      sustained, mild elevation in plasma NEFA is sufficient to increase TLR expression
      and TLR-driven signalling (NFkappaB and MAPK) in lean individuals. The activation
      of this pathway by NEFA may be involved in the pathogenesis of insulin resistance
      in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT01740817.

PMID- 24337157
TI  - The revolving door of 'residual beta cell function': cause or effect in medical
      reports?

PMID- 24337156
TI  - Exendin-4 is effective against metabolic disorders induced by intrauterine and
      postnatal overnutrition in rodents.
AB  - AIMS/HYPOTHESIS: Maternal obesity leads to increased adiposity, hyperlipidaemia
      and glucose intolerance in offspring. The analogue of glucagon-like peptide-1,
      exendin-4 (Ex-4), has been shown to induce weight loss in both adolescence and
      adulthood. We hypothesised that, in rats, daily injection of Ex-4 would reduce
      body fat and improve metabolic disorders in offspring from obese dams, especially
      those consuming a high-fat diet (HFD). METHODS: Female Sprague Dawley rats were
      fed chow or an HFD for 5 weeks before mating, and throughout gestation and
      lactation. At postnatal day 20, male pups from HFD-fed mothers were weaned onto
      chow or HFD and those from chow-fed mothers were fed chow. Within each dietary
      group, half of the pups were injected with Ex-4 (15 MUg/kg/day i.p.) for 6 weeks,
      while the other half received saline. RESULTS: Maternal obesity alone or combined
      with postweaning HFD consumption led to increased adiposity, hyperinsulinaemia,
      hyperlipidaemia, inflammation and impaired regulation of hypothalamic appetite
      regulators by glucose in offspring, while glucose intolerance was only observed
      in HFD-fed rats from obese dams. Ex-4 injection significantly reduced adiposity,
      hyperlipidaemia and insulin resistance in HFD-fed rats from obese dams. It also
      restored glucose tolerance and the lipid-lowering effect of blood glucose.
      However, Ex-4 did not change hypothalamic appetite regulation or the response of
      appetite regulators to hyperglycaemia. Liver and adipose inflammatory cytokine
      expression was significantly reduced by Ex-4. CONCLUSIONS/INTERPRETATION: Ex-4
      reversed the detrimental impact of maternal obesity on lipid and glucose
      metabolism in offspring regardless of diet, supporting its potential application
      in reducing metabolic disorders in high-risk populations.

PMID- 24337158
TI  - Catheter-tissue contact force for pulmonary veins isolation: a pilot multicentre
      study on effect on procedure and fluoroscopy time.
AB  - AIMS: Catheter-tissue contact is critical for effective lesion creation in
      radiofrequency catheter ablation (RFCA). In a multicentre prospective study, we
      assessed the effect of direct contact force (CF) measurement on acute procedural
      parameters during RFCA of atrial fibrillation (AF). METHODS AND RESULTS: A new
      open-irrigated tip catheter with CF sensing (SmartTouchTM, Biosense Webster Inc.)
      was used. All the patients underwent the first ablation procedure for paroxysmal
      AF with antral pulmonary vein (PV) isolation, aiming at entry and exit conduction
      block in all PVs. Ninety-five patients were enroled in nine centres and
      successfully underwent ablation. Overall procedure time, fluoroscopy time, and
      ablation time were 138.0 +/- 67.0, 14.3 +/- 11.2, and 33.8 +/- 19.4 min,
      respectively. The mean CF value during ablation was 12.2 +/- 3.9 g. Force time
      integral (FTI) analysis showed that patients achieving a value below the median
      of 543.0gs required longer procedural (158.0 +/- 74.0 vs. 117.0 +/- 52.0 min, P =
      0.004) and fluoroscopy (17.5 +/- 13.0 vs. 11.0 +/- 7.7 min, P = 0.007) times as
      compared with those in whom FTI was above this value. Patients in whom the mean
      CF during ablation was >20 g required shorter procedural time (92.0 +/- 23.0 vs.
      160.0 +/- 67.0 min, P = 0.01) as compared with patients in whom this value was
      <10 g. Four groin haematomas were the only complications observed. CONCLUSION:
      Contact force during RFCA for PV isolation affects procedural parameters, in
      particular procedural and fluoroscopy times, without increasing complications.

PMID- 24337159
TI  - Versatile multi-functionalization of protein nanofibrils for biosensor
      applications.
AB  - Protein nanofibrils offer advantages over other nanostructures due to the ease in
      their self-assembly and the versatility of surface chemistry available. Yet, an
      efficient and general methodology for their post-assembly functionalization
      remains a significant challenge. We introduce a generic approach, based on
      biotinylation and thiolation, for the multi-functionalization of protein
      nanofibrils self-assembled from whey proteins. Biochemical characterization shows
      the effects of the functionalization onto the nanofibrils' surface, giving
      insights into the changes in surface chemistry of the nanostructures. We show how
      these methods can be used to decorate whey protein nanofibrils with several
      components such as fluorescent quantum dots, enzymes, and metal nanoparticles. A
      multi-functionalization approach is used, as a proof of principle, for the
      development of a glucose biosensor platform, where the protein nanofibrils act as
      nanoscaffolds for glucose oxidase. Biotinylation is used for enzyme attachment
      and thiolation for nanoscaffold anchoring onto a gold electrode surface.
      Characterization via cyclic voltammetry shows an increase in glucose-oxidase
      mediated current response due to thiol-metal interactions with the gold
      electrode. The presented approach for protein nanofibril multi-functionalization
      is novel and has the potential of being applied to other protein nanostructures
      with similar surface chemistry. 

PMID- 24337160
TI  - Epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3
      deazaneplanocin A inhibits the growth of cholangiocarcinoma cells.
AB  - Enhancer of zeste homolog 2 (EZH2) is involved in malignant transformation and
      the biological aggressiveness of several human malignancies. Growing evidence
      indicates that EZH2 may be an appropriate therapeutic target for malignancies,
      including cholangiocarcinoma. Recently, an S-adenosyl-L-homocysteine hydrolase
      inhibitor, 3-deazaneplanocin A (DZNep) was shown to deplete and inhibit EZH2. The
      aim of this study was to determine the effect of DZNep and the combination of
      gemcitabine and DZNep in cholangiocarcinoma cells. The effects of DZNep and its
      combination with gemcitabine were assessed in the cholangiocarcinoma cell lines
      RBE and TFK-1. DZNep depleted the cellular levels of EZH2 and inhibited the
      associated histone H3 lysine 27 trimethylation. DZNep treatment resulted in the
      inhibition of proliferation in the cholangiocarcinoma cell lines, and the
      combination of DZNep and gemcitabine showed synergistic inhibition of cell
      proliferation. DZNep induced apoptosis and G1 phase cell cycle arrest in
      cholangiocarcinoma cells, and the combination of DZNep and gemcitabine enhanced
      the induced apoptosis and G1 arrest when compared with gemcitabine alone.
      Inhibition of cell proliferation by DZNep was partially associated with
      upregulation of p16INK4a and p17KIP1. The present study shows that DZNep inhibits
      cell proliferation by inducing G1 arrest and apoptosis. These results indicate
      that an epigenetic therapy that pharmacologically targets EZH2 via DZNep may
      constitute a novel approach for the treatment of cholangiocarcinoma.

PMID- 24337161
TI  - Bowen's disease: A six-year retrospective study of treatment with emphasis on
      resection margins.
AB  - Bowen's disease is an in situ squamous cell carcinoma of the skin with various
      treatment modalities available. A major advantage of surgical excision is the
      opportunity to histologically examine the resection margins. There is no
      consensus about the most appropriate margin. This retrospective study evaluates
      the clearance rates achieved by excision with a 5 mm margin and estimates how
      that might change after fictitiously reducing the resection margin by 1 or 2 mm.
      Patients with histologically confirmed Bowen's disease were selected at the
      Maastricht University Medical Centre from 2002 until 2007. Surgical margins and
      complete excision rates were evaluated and histological slides were re-examined.
      To our knowledge this is the first study investigating the safety margin for
      Bowen's disease. As Bowen's disease is not an invasive disease, minimisation of
      healthy tissue excision is desirable. Our data show that a hypothetical reduction
      of the safety margin from 5 mm to 4 or 3 mm decreases the complete excision rate
      from 94.4% to 87% and 74.1%, respectively. 

PMID- 24337162
TI  - Phenotypic characteristics associated with reduced short physical performance
      battery score in COPD.
AB  - BACKGROUND: The Short Physical Performance Battery (SPPB) is commonly used in
      gerontology, but its determinants have not been previously evaluated in COPD. In
      particular, it is unknown whether pulmonary aspects of COPD would limit the value
      of SPPB as an assessment tool of lower limb function. METHODS: In 109 patients
      with COPD, we measured SPPB score, spirometry, 6-min walk distance, quadriceps
      strength, rectus femoris cross-sectional area, fat-free mass, physical activity,
      health status, and Medical Research Council dyspnea score. In a subset of 31
      patients with COPD, a vastus lateralis biopsy was performed, and the biopsy
      specimen was examined to evaluate the structural muscle characteristics
      associated with SPPB score. The phenotypic characteristics of patients stratified
      according to SPPB were determined. RESULTS: Quadriceps strength and 6-min walk
      distance were the only independent predictors of SPPB score in a multivariate
      regression model. Furthermore, while age, dyspnea, and health status were also
      univariate predictors of SPPB score, FEV 1 was not. Stratification by reduced
      SPPB score identified patients with locomotor muscle atrophy and increasing
      impairment in strength, exercise capacity, and daily physical activity. Patients
      with mild or major impairment defined as an SPPB score < 10 had a higher
      proportion of type 2 fibers (71% [14] vs 58% [15], P = .04). CONCLUSIONS: The
      SPPB is a valid and simple assessment tool that may detect a phenotype with
      functional impairment, loss of muscle mass, and structural muscle abnormality in
      stable patients with COPD.

PMID- 24337163
TI  - ToF-SIMS analysis of poly(L-lysine)-graft-poly(2-methyl-2-oxazoline) ultrathin
      adlayers.
AB  - Understanding of the interfacial chemistry of ultrathin polymeric adlayers is
      fundamentally important in the context of establishing quantitative design rules
      for the fabrication of nonfouling surfaces in various applications such as
      biomaterials and medical devices. In this study, seven poly(L-lysine)-graft
      poly(2-methyl-2-oxazoline) (PLL-PMOXA) copolymers with grafting density (number
      of PMOXA chains per lysine residue) 0.09, 0.14, 0.19, 0.33, 0.43, 0.56, and 0.77,
      respectively, were synthesized and characterized by means of nuclear magnetic
      resonance spectroscopy (NMR). The copolymers were then adsorbed on Nb2O5
      surfaces. Optical waveguide lightmode spectroscopy method was used to monitor the
      surface adsorption in situ of these copolymers and provide information on adlayer
      masses that were then converted into PLL and PMOXA surface densities. To
      investigate the relationship between copolymer bulk architecture (as shown by NMR
      data) and surface coverage as well as surface architecture, time-of-flight
      secondary ion mass spectrometry (ToF-SIMS) analysis was performed. Furthermore,
      ToF-SIMS method combined with principal component analysis (PCA) was used to
      verify the protein resistant properties of PLL-PMOXA adlayers, by thorough
      characterization before and after adlayer exposure to human serum. ToF-SIMS
      analysis revealed that the chemical composition as well as the architecture of
      the different PLL-PMOXA adlayers indeed reflects the copolymer bulk composition.
      ToF-SIMS results also indicated a heterogeneous surface coverage of PLL-PMOXA
      adlayers with high grafting densities higher than 0.33. In the case of protein
      resistant surface, PCA results showed clear differences between protein resistant
      and nonprotein-resistant surfaces. Therefore, ToF-SIMS results combined with PCA
      confirmed that the PLL-PMOXA adlayer with brush architecture resists protein
      adsorption. However, low increases of some amino acid signals in ToF-SIMS spectra
      were detected after the adlayer has been exposed to human serum. 

PMID- 24337164
TI  - Metabolic pathway elucidation towards time- and dose-dependent electrophoretic
      screening of stable oxidative phenolic compounds.
AB  - This study demonstrates an untested link between model phenolic compounds and the
      formation/electrophoretic separation of stable urinary metabolites. Sterically
      encumbered carbonyl groups were examined, and mass determination was used to
      confirm the presence and stability of two oxidative metabolites of
      pentachlorophenol: tetrachloro-1,2-benzoquinone and tetrachloro-1,4
      dihydroquinone. Subsequently, baseline resolved separation of pentachlorophenol
      and the two oxidative metabolites was demonstrated under the following
      conditions: 75 mM sodium tetraborate buffer (pH = 8.5) with 5 % methanol and 50
      mM SDS, +10.0 kV running voltage, injection time = 5.0 s, effective capillary
      length = 55 cm, and run temperature = 20  degrees C. Results not only provide key
      metabolic inferences for pentachlorophenol, they also exhibit improvements in the
      ability to separate and detect changes in urinary metabolites in response to
      phenolic-related exposure. 

PMID- 24337165
TI  - Natural product synthesis in the age of scalability.
AB  - The ability to procure useful quantities of a molecule by simple, scalable routes
      is emerging as an important goal in natural product synthesis. Approaches to
      molecules that yield substantial material enable collaborative investigations
      (such as SAR studies or eventual commercial production) and inherently spur
      innovation in chemistry. As such, when evaluating a natural product synthesis,
      scalability is becoming an increasingly important factor. In this Highlight, we
      discuss recent examples of natural product synthesis from our laboratory and
      others, where the preparation of gram-scale quantities of a target compound or a
      key intermediate allowed for a deeper understanding of biological activities or
      enabled further investigational collaborations. 

PMID- 24337166
TI  - An analytical approach to investigate the evolution of bone volume fraction in
      bone remodeling simulation at the tissue and cell level.
AB  - Simulation of bone remodeling at the bone cell level can predict changes in bone
      microarchitecture and density due to bone diseases and drug treatment. Their
      clinical application, however, is limited since bone microarchitecture can only
      be measured in the peripheral skeleton of patients and since the simulations are
      very time consuming. To overcome these issues, we have developed an analytical
      model to predict bone density adaptation at the organ level, in agreement with
      our earlier developed bone remodeling theory at the cellular level. Assuming a
      generalized geometrical model at the microlevel, the original theory was
      reformulated into an analytical equation that describes the evolution of bone
      density as a function of parameters that describe cell activity,
      mechanotransduction and mechanical loading. It was found that this analytical
      model can predict changes in bone density due to changes in these cell-level
      parameters that are in good agreement with those predicted by the earlier
      numerical model that implemented a detailed micro-finite element (FE) model to
      represent the bone architecture and loading, at only a fraction of the
      computational costs. The good agreement between analytical and numerical density
      evolutions indicates that the analytical model presented in this study can
      predict well bone functional adaptation and, eventually, provide an efficient
      tool for simulating patient-specific bone remodeling and for better prognosis of
      bone fracture risk. 

PMID- 24337167
TI  - Transperineal template prostate biopsies in men with raised PSA despite two
      previous sets of negative TRUS-guided prostate biopsies.
AB  - BACKGROUND: The possibility of prostate cancer as a cause for steadily rising PSA
      despite previously negative transrectal ultrasound (TRUS)-guided prostate
      biopsies is a major concern. An initial negative TRUS-guided prostate biopsy does
      not necessarily exclude the presence of clinically significant prostate cancer.
      We determined the role of transperineal template prostate biopsy (TPTPB) in
      prostate cancer detection in men with raised PSA despite two previous sets of
      negative TRUS biopsies. METHODS: Between January 2008 and August 2012, a total of
      122 men's records were reviewed after having 36-core TPTPB following two previous
      sets of negative TRUS biopsies despite raised PSA. A retrospective record of PSA
      levels, clinicopathological parameters and histological outcomes was made.
      RESULTS: Mean age was 63 years (range 49-77), and mean PSA was 18.0 (range 2.0
      119.0). A total of 71/122 (58 %) men were diagnosed with prostate cancer on
      TPTPB. Of these, 28 (39 %), 34 (48 %), 5 (7 %), and 4 (6 %) had Gleason score 6,
      7 (3 + 4), 7 (4 + 3), and 9 (4 + 5), respectively. The mean number of positive
      cores was 7 (range 1-22). Of these, only 15 (21 %) had <=2 cores positive and
      Gleason score of 6. Of the 51 (42 %) men with a negative histology on TPTPB, 11
      (22 %), 10 (19 %), and 30 (59 %) had atypical small acinar proliferation, high
      grade prostatic intraepithelial neoplasia, or benign pathology. CONCLUSION: TPTPB
      is associated with a high rate of clinically significant prostate cancer
      diagnosis (58 %) in men with raised PSA despite two previous sets of negative
      TRUS biopsies.

PMID- 24337168
TI  - Incorporating population-level variability in orthopedic biomechanical analysis:
      a review.
AB  - Effectively addressing population-level variability within orthopedic analyses
      requires robust data sets that span the target population and can be greatly
      facilitated by statistical methods for incorporating such data into functional
      biomechanical models. Data sets continue to be disseminated that include not just
      anatomical information but also key mechanical data including tissue or joint
      stiffness, gait patterns, and other inputs relevant to analysis of joint function
      across a range of anatomies and physiologies. Statistical modeling can be used to
      establish correlations between a variety of structural and functional biometrics
      rooted in these data and to quantify how these correlations change from health to
      disease and, finally, to joint reconstruction or other clinical intervention.
      Principal component analysis provides a basis for effectively and efficiently
      integrating variability in anatomy, tissue properties, joint kinetics, and
      kinematics into mechanistic models of joint function. With such models,
      bioengineers are able to study the effects of variability on biomechanical
      performance, not just on a patient-specific basis but in a way that may be
      predictive of a larger patient population. The goal of this paper is to
      demonstrate the broad use of statistical modeling within orthopedics and to
      discuss ways to continue to leverage these techniques to improve biomechanical
      understanding of orthopedic systems across populations. 

PMID- 24337169
TI  - Characterization of a new picornavirus isolated from the freshwater fish Lepomis
      macrochirus.
AB  - The freshwater fish Lepomis macrochirus (bluegill) is common to North American
      waters, and important both ecologically and as a sport fish. In 2001 an unknown
      virus was isolated from bluegills following a bluegill fish kill. This virus was
      identified as a picornavirus [termed bluegill picornavirus (BGPV)] and a
      diagnostic reverse transcriptase PCR was developed. A survey of bluegills in
      Wisconsin waters showed the presence of BGPV in 5 of 17 waters sampled,
      suggesting the virus is widespread in bluegill populations. Experimental
      infections of bluegills confirmed that BGPV can cause morbidity and mortality in
      bluegills. Molecular characterization of BGPV revealed several distinct genome
      characteristics, the most unusual of which is the presence of a short poly(C)
      tract in the 3' UTR. Additionally, the genome encodes a polyprotein lacking a
      leader peptide and a VP0 maturation cleavage site, and is predicted to encode two
      distinct 2A proteins. Sequence comparison showed that the virus is most closely
      related to a phylogenetic cluster of picornaviruses that includes the genera
      Aquamavirus, Avihepatovirus and Parechovirus. However, it is distinct enough, for
      example sharing only about 38% sequence identity to the parechoviruses in the 3D
      region, that it may represent a new genus in the family Picornaviridae.

PMID- 24337170
TI  - Checks and balances between human cytomegalovirus replication and indoleamine-2,3
      dioxygenase.
AB  - Despite a rigorous blockade of interferon-gamma (IFN-gamma) signalling in
      infected fibroblasts as a mechanism of immune evasion by human cytomegalovirus
      (HCMV), IFN-gamma induced indoleamine-2,3-dioxygenase (IDO) has been proposed to
      represent the major antiviral restriction factor limiting HCMV replication in
      epithelial cells. Here we show that HCMV efficiently blocks transcription of IFN
      gamma-induced IDO mRNA both in infected fibroblasts and epithelial cells even in
      the presence of a preexisting IFN-induced antiviral state. This interference
      results in severe suppression of IDO bioactivity in HCMV-infected cells and
      restoration of vigorous HCMV replication. Depletion of IDO expression nonetheless
      substantially alleviated the antiviral impact of IFN-gamma treatment in both cell
      types. These findings highlight the effectiveness of this IFN-gamma induced
      effector gene in restricting HCMV productivity, but also the impact of viral
      counter-measures. 

PMID- 24337171
TI  - Tissue engineering for plastic surgeons: a primer commentary.

PMID- 24337172
TI  - Modified tumescent superficial suction with curettage treatment for axillary
      bromidrosis: clinical experience of 280 cases.
AB  - BACKGROUND: Axillary bromidrosis adversely affects patients' social and personal
      life with excessive malodor. Although surgical resection of the apocrine glands
      is one effective and irreversible method for treating axillary bromidrosis, the
      postoperation complications cannot be ignored. This study aimed to evaluate the
      long-term outcome of the authors' modified tumescent superficial suction with a
      curettage procedure for axillary bromidrosis treatment. METHODS: From January
      2010 to December 2012, 450 patients with axillary bromidrosis visited the
      authors' plastic surgery outpatient department and received the modified treated
      using tumescent superficial suction with a curettage procedure. A total of 170
      patients were lost to follow-up evaluation and eliminated from this study.
      RESULTS: The follow-up period ranged from 5 to 35 months (mean 15.5 months).
      Among 280 patients, 261 (93.2 %) showed excellent to good results. Reoperation
      with the same procedure was performed for 15 patients, and all had excellent
      results afterward. The most common postoperative complication was transient
      ecchymosis (23.6 %). CONCLUSION: The modified suction and curettage procedure is
      an optimal therapeutic strategy for axillary bromidrosis treatment. LEVEL OF
      EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24337173
TI  - Capsular grafts and flaps in immediate prosthetic breast reconstruction.
AB  - BACKGROUND: Patients with previously augmented breasts and a diagnosis of breast
      cancer who are candidates for immediate prosthetic reconstruction can benefit
      from capsular tissues used for splinting the position of the pectoralis major
      muscle. METHODS: A retrospective clinical review of patients with previously
      augmented breasts who are undergoing mastectomy and immediate prosthetic
      reconstruction with capsular tissues was undertaken. The bottom of the
      periprosthetic capsule was tailored in a novel and versatile fashion as grafts or
      flaps and used as a sling between the pectoralis major and the inframammary fold.
      RESULTS: Of the 21 patients in this study, 19 had unilateral reconstruction,
      whereas 2 had bilateral reconstructions. Capsular tissues were harvested as free
      capsular grafts in 15 cases and raised as a capsular flap in the remaining 8
      cases. During the follow-up period, complications were detected in 7 patients (1
      seroma, 1 infection, 1 hematoma, 1 superficial epidermolysis, 2 cases of
      rippling, and 1 mild capsular contracture). CONCLUSIONS: For eligible patients,
      the use of capsular tissues offers a readily available and cost-effective
      alternative to acellular dermal matrices with a negligible complication rate.
      Patient selection is key to ensuring a safe oncologic approach and must be
      carefully carried out in close collaboration with the breast surgeon. LEVEL OF
      EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24337174
TI  - Crosstalk between mitochondrial ROS and depolarization in the potentiation of
      TRAIL-induced apoptosis in human tumor cells.
AB  - We previously showed that membrane-depolarizing agents such as K+ and ATP
      sensitive potassium (KATP) channel inhibitors potentiate tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human melanoma
      cells, but not in normal melanocytes. In this study, we investigated whether the
      tumor-selective effect of depolarization was observed among different tumor cell
      types and the mechanisms by which depolarization potentiates death pathways. We
      found that K+ and KATP channel inhibitors elicited similar apoptosis-potentiating
      effects in human tumor cells with different origins, including leukemia, melanoma
      and lung cancer cells. In contrast, minimal potentiation of apoptosis was
      observed in non-transformed lung cells. The potentiation was associated with
      increased mitochondrial and endoplasmic reticulum stress death pathways.
      Upregulation of surface TRAIL receptor-2 expression and modulation of the caspase
      3 activation pathway seemed to play roles in the enhancement of death signaling.
      Moreover, the results showed that depolarization and mitochondria-derived
      reactive oxygen species (mROS) mutually regulated one another. Depolarization
      potentiated TRAIL-induced mROS accumulation. Conversely, scavenging of mROS by
      the antioxidant MnTBaP reduced depolarization, whereas mROS accumulation caused
      by metabolic inhibitors potentiated the depolarization. These findings suggest a
      positive loop between depolarization and mROS accumulation. This may provide a
      rationale for the tumor-selective cytotoxicity and/or potentiation of TRAIL
      cytotoxicity of a wide variety of ROS-producing substances in different types of
      tumor cells. 

PMID- 24337175
TI  - Cough in asthma is due to eosinophilic airway inflammation: a pro/con debate.
AB  - Multiple prospective studies have demonstrated that asthma is among the most
      common etiologies of chronic cough, along with upper-airway cough syndrome
      (formerly known as postnasal drip syndrome) and gastroesophageal reflux disease.
      More recently, the entity of nonasthmatic eosinophilic bronchitis has been
      appreciated as a significant cause of chronic cough worldwide. Chronic cough
      associated with both of these conditions typically responds well to therapy with
      systemic or inhaled corticosteroids, thus leading to a general assumption that
      the suppression of eosinophilic airway inflammation explains the improvement in
      cough. However, some recent studies challenge a causal relationship between
      eosinophilic airway inflammation and cough in asthmatics. The 4th American Cough
      Conference, held in New York in June 2013, provided an ideal forum for discussion
      and debate of this issue between two internationally recognized experts in the
      field of asthma and chronic cough. 

PMID- 24337176
TI  - Association analysis of IL7R polymorphisms with inflammatory demyelinating
      diseases.
AB  - Multiple sclerosis (MS) and neuromyelitis optica (NMO), which are referred to as
      inflammatory demyelinating diseases (IDDs), are autoimmune diseases affecting the
      central nervous system. Interleukin-7 receptor (IL7R) encodes for a receptor
      protein that is important in the development of immune cells. Several studies
      have reported significant associations between IL7R polymorphisms and MS. The aim
      of the present study was to investigate a possible association between IL7R
      polymorphisms and IDDs such as MS and NMO. Thirteen single nucleotide
      polymorphisms (SNPs) were selected based on their linkage disequilibrium (LD),
      minor allele frequency (MAF) and location, and were genotyped in 178 IDD patients
      and 237 healthy controls. The association of SNPs with IDD risk was analyzed by
      logistic regression. A meta-analysis on the association between rs6897932 and the
      risk of MS was also performed. Statistical analyses revealed that a common SNP,
      rs6897932, was marginally associated with IDD in a recessive model (P=0.003,
      Pcor.=0.03), which had shown significant associations with MS in previous
      studies. The results replicated the significant association found between
      rs6897932 and IDD. In addition, the meta-analysis of rs6897932 clearly
      demonstrates a higher magnitude of risk in Asian populations than in Caucasian
      populations. Although there are certain limitations to our study, the results
      indicate that the genetic variation of IL7R may be associated with IDDs such as
      MS and NMO in the population studied.

PMID- 24337177
TI  - [Surgical interventions in patients with mast cell activation disease. Aspects
      relevant for surgery using the example of a cholecystectomy].
AB  - BACKGROUND: Systemic mast cell activation disease (MCAD) is characterized by an
      increased and unregulated release of mast cell mediators which can evoke a
      multifaceted clinical picture often resembling irritable bowel syndrome or
      fibromyalgia. Because of the considerable prevalence (~ 17 %) of MCAD surgeons
      are frequently unwittingly confronted with MCAD patients in whom unexpected
      intraoperative and postoperative complications may occur. Therefore, knowledge of
      the particular requirements is of relevance for surgical treatment of MCAD
      patients. OBJECTIVE: The present paper outlines a concept of surgical treatment
      of MCAD patients based on the literature which is illustrated by a case report on
      emergency laparoscopic cholecystectomy. CONCLUSIONS: Due to the high prevalence
      of MCAD in the general population it can be assumed that the frequency in the
      surgical patient population is similar. If a patient has MCAD, specific
      characteristics should be taken into account in the surgical procedure to avoid
      increased operative and complication risks resulting from MCAD.

PMID- 24337178
TI  - Novel strain of Spiroplasma found in flower bugs of the genus Orius (Hemiptera:
      Anthocoridae): transovarial transmission, coexistence with Wolbachia and varied
      population density.
AB  - Spiroplasma, a group of small, wall-less, helical, and motile bacteria belonging
      to the Mollicutes, contains species with diverse life histories. To date, all the
      Spiroplasma strains that are known to be transmitted vertically in arthropod
      lineages belong to either the Spiroplasma ixodetis group or the Spiroplasma
      poulsonii group. Here, we found that a unique strain of Spiroplasma vertically
      transmitted in predatory flower bugs of the genus Orius belongs to the
      Spiroplasma insolitum group, which is a group of bacteria phylogenetically
      closely related to S. insolitum derived from the tickseed sunflower, Bidens sp.
      (Asterales: Asteraceae). The infection frequencies in natural populations
      were16.0% in Orius sauteri (n = 75), 40.5% in Orius nagaii (n = 37), and 8.0% in
      Orius minutus (n = 87). Orius strigicollis was not infected with Spiroplasma (n =
      147). In the early stage of oogenesis (i.e., within the germarium), a large
      number of bacteria with the typical morphology of Spiroplasma existed, keeping a
      distance from Wolbachia bacteria. The Spiroplasma population seemed to increase
      during host development but Wolbachia population did not.

PMID- 24337179
TI  - Enzyme-assisted extraction of kappa/iota-hybrid carrageenan from Mastocarpus
      stellatus for obtaining bioactive ingredients and their application for edible
      active film development.
AB  - Two hydrolysates were obtained from dried Mastocarpus stellatus using alcalase.
      The phenolic content was partially removed from one of them. The phenolic
      partially-removed hydrolysate (H) was found to be a potent angiotensin-I
      converting enzyme (ACE) inhibitor. However, the phenolic-containing hydrolysate
      (Hp) showed a higher Folin-reactive substance content and antioxidant capacity
      (reducing power and radical scavenging capacity). Hp was therefore selected for
      the development of antioxidant Mastocarpus carrageenan-based films. F-Hp0
      (without the hydrolysate), F-Hp15 (with 15% hydrolysate) and F-Hp30 (with 30%
      hydrolysate) films were developed. kappa/iota-hybrid carrageenan was the main
      film constituent and hydrolysate addition resulted in an increased sulfated
      proportion, higher protein content and higher number of hydrogen bonds. Therefore
      interactions between carrageenan helices, plasticizers and peptides in the film
      forming solution were enhanced, especially in F-Hp15, and consequently the water
      vapour permeability (WVP) of the resulting film decreased. Nevertheless, F-Hp30
      considerably improved the transparency, UV/Vis light barrier, water resistance
      and elongation at break (EAB). The presence of Hp increased both puncture force
      (F) and puncture elongation (E), but not tensile strength (TS) or Young's modulus
      (Y). The addition of an increased concentration of hydrolysate to the films led
      to a considerable increase in the Folin-reactive substance content and the
      antioxidant activity, especially the radical scavenging capacity. 

PMID- 24337180
TI  - Subject-specific finite element modeling of the tibiofemoral joint based on CT,
      magnetic resonance imaging and dynamic stereo-radiography data in vivo.
AB  - In this paper, we present a new methodology for subject-specific finite element
      modeling of the tibiofemoral joint based on in vivo computed tomography (CT),
      magnetic resonance imaging (MRI), and dynamic stereo-radiography (DSX) data. We
      implemented and compared two techniques to incorporate in vivo skeletal
      kinematics as boundary conditions: one used MRI-measured tibiofemoral kinematics
      in a nonweight-bearing supine position and allowed five degrees of freedom
      (excluding flexion-extension) at the joint in response to an axially applied
      force; the other used DSX-measured tibiofemoral kinematics in a weight-bearing
      standing position and permitted only axial translation in response to the same
      force. Verification and comparison of the model predictions employed data from a
      meniscus transplantation study subject with a meniscectomized and an intact knee.
      The model-predicted cartilage-cartilage contact areas were examined against
      "benchmarks" from a novel in situ contact area analysis (ISCAA) in which the
      intersection volume between nondeformed femoral and tibial cartilage was
      characterized to determine the contact. The results showed that the DSX-based
      model predicted contact areas in close alignment with the benchmarks, and
      outperformed the MRI-based model: the contact centroid predicted by the former
      was on average 85% closer to the benchmark location. The DSX-based FE model
      predictions also indicated that the (lateral) meniscectomy increased the contact
      area in the lateral compartment and increased the maximum contact pressure and
      maximum compressive stress in both compartments. We discuss the importance of
      accurate, task-specific skeletal kinematics in subject-specific FE modeling,
      along with the effects of simplifying assumptions and limitations.

PMID- 24337181
TI  - Public-private relationships in biobanking: a still underestimated key component
      of open innovation.
AB  - Access to human bioresources is essential to the understanding of human diseases
      and to the discovery of new biomarkers aimed at improving the diagnosis,
      prognosis, and the predictive response of patients to treatments. The use of
      biospecimens is strictly controlled by ethical assessment, which complies with
      the laws of the country. These laws regulate the partnerships between the
      biobanks and industrial actors. However, private-public partnerships (PPP) can be
      limiting for several reasons, which can hamper the discovery of new biological
      tests and new active molecules targeted to human diseases. The bottlenecks and
      roadblocks in establishing these partnerships include: poor organization of the
      biobank in setting up PPP, evaluation of the cost of human samples, the absence
      of experience on the public side in setting up contracts with industry, and the
      fact that public and private partners may not share the same objectives. However,
      it is critical, in particular for academic biobanks, to establish strong PPP to
      accelerate translational research for the benefits of patients, and to allow the
      sustainability of the biobank. The purpose of this review is to discuss the main
      bottlenecks and roadblocks that can hamper the establishment of PPP based on
      solid and trusting relationships. 

PMID- 24337182
TI  - Fatty acid synthase overexpression in adult testicular germ cell tumors:
      potential role in the progression of non-seminomatous germ cell tumors.
AB  - Overexpression of fatty acid synthase (FASN), which is a key enzyme responsible
      for the endogenous synthesis of fatty acids, and its association with multistep
      progression have been demonstrated in various human malignant tumors. We aimed to
      clarify the potential role of FASN overexpression in the development and
      progression of adult testicular germ cell tumors (TGCTs). From the primary sites
      of a cohort of 113 TGCT cases, we obtained 221 histological components: 53
      intratubular germ cell neoplasias, unclassified (IGCNUs), 84 seminomas, 32
      embryonal carcinomas, seven choriocarcinomas, 21 yolk sac tumors, and 24
      teratomas. Samples were analyzed for overexpression of FASN by
      immunohistochemistry. Intensities of immunoreactivity and the fraction of
      positive cells were classified into each four categories (intensity, 0 to 3;
      fraction, 0-10 % = 1, 11-50 % = 2, 51-80 % = 3, and >80 % = 4). The overall score
      was determined by multiplication of both scores and overall scores greater than 6
      were considered FASN overexpression. On a component basis, FASN overexpression
      was detected in 8 % of seminomas but not in IGCNUs (0 %) and was detected
      frequently in non-seminomatous germ cell tumors (NSGCTs) (88 % of embryonal
      carcinomas, all choriocarcinomas, 81 % of yolk sac tumors, and 54 % of
      teratomas). There were no cases of a mixed tumor (i.e., a tumor with multiple
      histological components) that overexpressed FASN in seminoma components but not
      in co-existing NSGCT components, suggesting sequential progression. Our
      immunohistochemical data suggest that FASN overexpression occurs as a late event
      during the progression from IGCNUs/seminomas to NSGCTs. 

PMID- 24337184
TI  - Thin-film microextraction coupled to LC-ESI-MS/MS for determination of quaternary
      ammonium compounds in water samples.
AB  - The dual nature of the quaternary ammonium compounds, having permanently charged
      hydrophilic quaternary ammonium heads and long-chain hydrophobic tails, makes the
      sample preparation step and analysis of these compounds challenging. A high
      throughput method based on thin-film solid-phase microextraction (SPME) and
      liquid chromatography mass spectrometry was developed for simultaneous
      quantitative analysis of nine benzylic and aliphatic quaternary ammonium
      compounds. Chromatographic separation and detection of analytes were obtained in
      reverse-phase mode in 8 min using a triple quadrupole mass spectrometer.
      Hydrophilic lipophilic balance particle-coated blades were found to be the most
      suitable among the different coatings tested in terms of recoveries and carryover
      on the blades. For desorption solvents, 70/30, v/v (A/B) with 0.1 % formic acid
      (where A is 10 mM ammonium acetate in acetonitrile/water (95/5 , v/v) and B is
      0.1 %  (v/v) formic acid in isopropyl alcohol) was shown to be the most efficient
      solvent for the desorption of the analytes from the SPME sorbent. The SPME method
      was optimised in terms of extraction, pH, and preconditioning, as well as
      extraction and desorption times. Optimum conditions were 45 min of extraction
      time and 15 min of desorption time, all with agitation. The extraction was found
      to be optimum in a range of pH 6.0 to 8.0, which is consistent with the natural
      pH of water samples. Wide linear dynamic ranges with the developed method were
      obtained for each compound, enabling the application of the method for a wide
      range of concentrations. The developed method was validated according to the Food
      and Drug Administration criteria. The proposed method is the first SPME-based
      approach describing the applicability of the high-throughput thin-film SPME in a
      96-well system for analysis of such challenging compounds.

PMID- 24337183
TI  - Silencing of Barkor/ATG14 sensitizes osteosarcoma cells to cisplatin-induced
      apoptosis.
AB  - Although surgical excision following neoadjuvant chemotherapy has contributed to
      the long-term survival of osteosarcoma patients, patients that do not respond to
      commonly used drugs including cisplatin, have a poor prognosis. Autophagy is
      important in the inhibition of chemotherapeutic apoptosis. Therefore, we
      investigated whether knockdown of Beclin1-associated autophagy-related key
      regulator (Barkor/ATG14) promoted cisplatin-induced apoptosis in a drug-resistant
      osteosarcoma cell line in vitro. Saos-2 cells were transfected with Barkor siRNA.
      Sensitivity of the Barkor siRNA-transfected cell line to cisplatin was evaluated.
      Silencing of Barkor did not directly inhibit the growth rate of the transfected
      cells, but it significantly increased their sensitivity to cisplatin. The results
      of flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining revealed that
      Barkor siRNA-transfected Saos-2 cells treated with cisplatin exhibited much
      higher rates of apoptosis than the control and control siRNA-transfected cells.
      Additionally, the combination of silencing of Barkor with cisplatin treatment
      promoted the expression of caspase-12 and calpain. The increase of cisplatin
      cytotoxicity may therefore be involved in endoplasmic reticulum (ER) stress
      associated apoptosis. Bcl-2 was markedly downregulated in dose-dependent
      cisplatin-treated Barkor-transfected-Saos-2 cells. Findings of the present study
      suggest that the combination of silencing of Barkor and cisplatin enhanced the
      antitumor efficacy through the Barkor-related ER- and mitochondrial-mediated
      apoptotic pathway.

PMID- 24337185
TI  - Study on the PK profiles of magnoflorine and its potential interaction in Cortex
      phellodendri decoction by LC-MS/MS.
AB  - Magnoflorine, an aporphine alkaloid in Cortex phellodendri, is increasingly
      attracting research attention because of its antidiabetic effects. However, at
      present, little information on its pharmacokinetics (PK) in vivo is available. In
      this study, a sensitive, rapid, and selective method was developed to determine
      the magnoflorine content in rat plasma using liquid chromatography-tandem mass
      spectrometry. Following liquid-liquid extraction, the calibration curve showed
      good linearity within the concentration range of 2.93 to 1,500 ng ml(-1). The
      intra- and inter-day precisions were all below 7.8 %, and the accuracy ranged
      from 94.9 to 103.4 %. The method was successfully applied in investigating the PK
      of magnoflorine in rats. The compound had low bioavailability, a high absorption
      rate, and a high elimination rate. However, area under the curve, T 1/2, and MRT
      increased approximately twofold when the same dosage of the compound was
      administered in a C. phellodendri decoction (20.8 g kg(-1)). Moreover, T max was
      prolonged from 0.3 to 3.33 h. Furthermore, a comparison of coadministration of
      the mixture group, magnoflorine (40 mg kg(-1)) and berberine (696.4 mg kg(-1)),
      with the C. phellodendri decoction group, revealed that no statistical difference
      (P > 0.05) was found in the parameter AUC, and certain similar changes in the PK
      trend to the herbal medicine group were also observed. These results suggested
      that oral administration of the herbal medicine decreased the absorption and
      elimination rates of magnoflorine and increased its bioavailability. Berberine
      played a significant role in interacting with magnoflorine and in affecting the
      PK profiles of magnoflorine in the C. phellodendri decoction group. 

PMID- 24337186
TI  - An alternative easy method for antibody purification and analysis of protein
      protein interaction using GST fusion proteins immobilized onto glutathione
      agarose.
AB  - Immobilization of small proteins designed to perform protein-protein assays can
      be a difficult task. Often, the modification of reactive residues necessary for
      the interaction between the immobilized protein and the matrix compromises the
      interaction between the protein and its target. In these cases, glutathione-S
      transferase (GST) is a valuable tag providing a long arm that makes the bait
      protein accessible to the mobile flow phase of the chromatography. In the present
      report, we used a GST fusion version of the 8-kDa protein serine protease
      inhibitor Kazal-type 3 (SPINK3) as the bait to purify anti-SPINK3 antibodies from
      a rabbit crude serum. The protocol for immobilization of GST-SPINK3 to
      glutathione-agarose beads was modified from previously reported protocols by
      using an alternative bifunctional cross-linker (dithiobis(succinimidyl
      propionate)) in a very simple procedure and by using simple buffers under
      physiological conditions. We concluded that the immobilized protein remained
      bound to the column after elution with low pH, allowing the reuse of the column
      for alternative uses, such as screening for other protein-protein interactions
      using SPINK3 as the bait. 

PMID- 24337187
TI  - LC-MS/MS in the routine clinical laboratory: has its time come?
AB  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been increasingly
      used in routine clinical laboratories during the last two decades. The high
      specificity, sensitivity, and multi-analyte potential make it an ideal
      alternative to immunoassays or conventional high-performance liquid
      chromatography (HPLC). It also provides higher throughput than gas chromatography
      mass spectrometry (GC-MS). LC-MS/MS also offers higher flexibility than
      immunoassays because LC-MS/MS assays are typically developed in-house. In
      addition, abundant information can be obtained from a single LC-MS/MS run which
      can produce a large amount of quantitative or qualitative data. In this review,
      typical LC-MS/MS clinical applications are presented, personal experiences are
      shared, and strengths and weakness are discussed. It is foreseeable that LC-MS/MS
      will become a key instrument in routine clinical laboratories. 

PMID- 24337188
TI  - Proteomic study of a tolerant genotype of durum wheat under salt-stress
      conditions.
AB  - Salinity is one of the major abiotic stress conditions limiting crop growth and
      productivity. Duilio is a wheat genotype that shows tolerant behavior in both
      salt-stress and drought-stress conditions. Toward better understanding of the
      biochemical response to salinity in this genotype of durum wheat, a comparative
      label-free shotgun proteomic analysis based on normalized spectral abundance
      factors was conducted on wheat leaf samples subjected to increasing salt-stress
      levels (100 and 200 mmol L(-1) NaCl) with respect to untreated samples. We found
      significant changes in 71 proteins for the first stress level, in 83 proteins at
      the higher salinity level, and in 88 proteins when comparing salt-stress levels
      with each other. The major changes concerned the proteins involved in primary
      metabolism and production of energy, followed by those involved in protein
      metabolism and cellular defense mechanisms. Some indications of different
      specific physiological and defense mechanisms implicated in increasing tolerance
      were obtained. The enhanced salinity tolerance in Duilio appeared to be governed
      by a higher capacity for osmotic homeostasis, a more efficient defense, and an
      improvement of protection from mechanical stress by increased cell wall
      lignifications, allowing a better potential for growth recovery. 

PMID- 24337190
TI  - Role of computed tomography scan for the primary surveillance of mucosal gastric
      cancer after complete resection by endoscopic submucosal dissection.
AB  - BACKGROUND: Abdominal computed tomography (CT) scan is periodically performed in
      almost all patients with early gastric cancer after undergoing endoscopic
      submucosal dissection (ESD). However, little is known about the diagnostic yield
      of CT scans for tumors that recurred after curative resection by ESD. METHODS: A
      total of 1,175 mucosal gastric cancers treated by ESD between January 2007 and
      December 2012 were retrospectively reviewed. Of them, 894 initial-onset early
      gastric cancers with two or more endoscopies with biopsy and one or more CT scans
      were included for survival analysis. RESULTS: The median follow-up period was
      19.7 months (interquartile range, 11.3-35.4 months), during which time 81 lesions
      recurred. Of these, 35 recurred as an adenoma, whereas the others recurred as
      cancer. Of the 81 lesions that recurred, 79 were not diagnosed by abdominal CT
      scan but rather by endoscopy with biopsy. The remaining two lesions, which
      recurred as metachronous cancers, had suspicious CT scan findings, such as focal
      gastric wall thickening. The lesions also were confirmed by endoscopic biopsy,
      which was performed on the same day. None of the lesions was diagnosed by CT scan
      before pathologic confirmation by endoscopic biopsy. CONCLUSIONS: Computed
      tomography scan has a minor role for the surveillance of mucosal gastric cancer
      after complete resection by ESD. Endoscopy with biopsy should be the primary
      surveillance option after ESD.

PMID- 24337189
TI  - Laparoscopic adrenal metastasectomy: appropriate, safe, and feasible.
AB  - BACKGROUND: The role of adrenalectomy in management of isolated metastatic
      adrenal tumors is increasingly established. Laparoscopy is becoming the preferred
      approach for these resections. We evaluated surgical and oncological outcomes of
      patients who underwent laparoscopic versus open adrenal metastasectomy and
      assessed the effect of such surgery on postoperative adjuvant therapy and
      survival. METHODS: We reviewed our institutional experience with adult patients
      who underwent an adrenal metastasectomy from 1997 to 2013. We assessed
      preoperative tumor size, operating room (OR) time, status of resection margin,
      and length of stay (LOS), as well as oncological outcomes including the use of
      adjuvant chemotherapy and radiotherapy within 1 year of surgery and 5-year
      survival. The chi (2) test, Mann-Whitney U test, and Kaplan-Meier curve were used
      for statistical analysis. RESULTS: Thirty-eight patients were identified. Lung
      was the primary site of malignancy (52.6 % of cases). Of the metastasectomies,
      55.2 % (n = 21) were performed laparoscopically and 44.7 % (n = 17) were open. In
      the laparoscopic group, median tumor size was 2.6 cm versus 4.8 cm in the open
      group (p = 0.09). Median OR time and complication rates were similar between the
      2 groups. The laparoscopic group, however, trended toward a shorter LOS (3 days
      laparoscopic vs. 4 days for open; p = 0.07). At 1 year, 37 % of all patients had
      not required any adjuvant chemotherapy or adjuvant radiotherapy. CONCLUSIONS:
      This series confirms that adrenal metastasectomy leads to favorable oncological
      outcomes in select patient groups, with over one-third of patients not requiring
      adjuvant therapy for at least 1 year after their resection. Laparoscopic approach
      leads to excellent oncological resection margins without increasing OR time and
      with a possible reduction in LOS.

PMID- 24337191
TI  - Cost savings for elective laparoscopic resection compared with open resection for
      colorectal cancer in a region of high uptake.
AB  - BACKGROUND: Previous cost analyses of laparoscopic resection for colorectal
      cancer (CRC) reported slightly higher or similar costs to those of open
      resection. These analyses were based on randomised controlled trials when the
      laparoscopic approach was newly adopted. This study compared costs for
      laparoscopic versus open resection in a region of high uptake where adoption is
      mature. METHODS: Hospital cost data were obtained for elective resections for CRC
      that occurred between June 2009 and June 2011 in public hospitals in Queensland,
      Australia. The primary outcome was total cost and secondary outcomes were length
      of-stay, operating time, and ICU admission. Multivariate least-squares regression
      was used to adjust for potential confounders: age, sex, comorbidities, procedure,
      and hospital volume. RESULTS: The crude mean cost for laparoscopic resection was
      euro 20,036 compared with that for open resection of euro 22,780 (difference =
      euro 2,744). Patients who underwent laparoscopic resection (744/1,397; 53 %) were
      slightly younger and had fewer comorbidities (decreasing costs) but more had
      rectal surgery (increasing costs). The adjusted mean cost for laparoscopic
      resection was euro 20,396 compared with euro 22,442 for open resection
      (difference = euro 2,054). Compared with open resection, when adjusted for
      potential confounders, laparoscopic resection resulted in similar operating time
      (216 vs. 214 min), shorter length-of-stay (difference = -1.1 days, 95 % CI -1.9, 
      0.3), and shorter admission to ICU (difference = -7.3 h, 95 % CI -11.9, -2.7).
      CONCLUSIONS: This non-randomised study in a region of high uptake found a similar
      operating time and lower cost for laparoscopic resection for CRC compared with
      those of open resection due to a shorter length-of-stay and shorter time in ICU.
      Laparoscopic resection for CRC saves money when the procedure is widely adopted
      and surgeons are experienced in the technique.

PMID- 24337192
TI  - Efficacy of the double-pigtail stent as a conservative treatment for grade B
      pancreatic fistula after pancreatoduodenectomy with pancreatogastric anastomosis.
AB  - BACKGROUND: Despite improvements in surgical techniques and postoperative care,
      morbidity associated with pancreatoduodenectomy (PD) is still high. Grade B
      pancreatic fistula (PF) requires a specific combination of radiologically guided
      external drainage and medical support. This treatment is effective but requires
      prolonged hospitalization and maintenance of external drainage. The objective of
      this study was to evaluate the feasibility and efficacy of a double-pigtail stent
      (DPS) to treat grade B PF after PD with pancreatogastric anastomosis. METHODS:
      Between January 2008 and October 2011, all patients who presented grade B PF
      after PD (n = 6) were included in the study. The PF was diagnosed according to
      the criteria of the International Study Group on Pancreatic Fistula. Endoscopic
      treatment was standardized with a DPS. The primary efficacy end point was the
      feasibility and efficacy of DPS placement. Secondary end points included data on
      the PF, the DPS placement procedure, and long-term outcome. RESULTS: Endoscopic
      DPS placement was achieved in all patients with no complications. The median time
      to onset of PF after PD was 14 days. Closure of the external PF was obtained 7
      days after the introduction of the DPS. The median time to external drain removal
      was 7 days after DPS placement, and the median time to oral refeeding was 7 days
      after DPS placement for all patients. The median time to DPS removal was 60 days.
      The median length of hospital stay after DPS placement was 10 days. During a
      median follow-up period of 21 months, there was no recurrence of PF after removal
      of the DPS. CONCLUSION: Endoscopic treatment of grade B PF after PD appears to be
      effective and safe and is associated with shorter hospitalization.

PMID- 24337193
TI  - Surfactant protein B gene polymorphism is associated with severe influenza.
AB  - BACKGROUND: Surfactant proteins play a key role in alveolar stability. We
      examined whether single nucleotide polymorphisms (SNPs) related to the surfactant
      protein genes are associated with severe influenza. METHODS: In the first cohort,
      12 SNPs related to surfactant protein genes were compared between Chinese
      patients with severe and mild pandemic 2009 influenza A(H1N1) (A[H1N1]pdm09)
      infection who were matched for age, sex, and underlying risk conditions. The SNP
      rs1130866, which was significantly different between the two groups, was further
      genotyped in a second cohort of patients. Multivariate analysis was performed to
      control for confounding factors. The genotype frequencies were also compared with
      those of the general Han Chinese population. RESULTS: This study consisted of 380
      patients with A(H1N1)pdm09 infection. In the first cohort of 84 patients, the C
      allele of rs1130866, an SNP in the surfactant protein B gene (SFTPB), was
      significantly associated with severe disease (OR = 3.37, P = .0048), although the
      P value was .057 after Bonferroni correction. In the second cohort of 296
      patients, the C/C genotype was confirmed in the univariate analysis to be
      associated with severe disease. Multivariate analysis of the second cohort showed
      that genotype C/C was an independent risk factor for severe A(H1N1)pdm09
      infection (second cohort: OR = 2.087, P = .023). Compared to the general Han
      Chinese population, the C/C genotype was overrepresented in patients with severe
      A(H1N1)pdm09 infection (OR = 3.232, P = .00000056). CONCLUSIONS: SFTPB
      polymorphism is associated with severe influenza. The role of SFTPB in influenza
      warrants further studies.

PMID- 24337194
TI  - Adoption potential of conservation agriculture practices in sub-Saharan Africa:
      results from five case studies.
AB  - Despite the reported benefits of conservation agriculture (CA), its wider up
      scaling in Sub-Saharan Africa (SSA) has remained fairly limited. This paper shows
      how a newly developed qualitative expert assessment approach for CA adoption
      (QAToCA) was applied to determine its adoption potential in SSA. CA adoption
      potential is not a predictor of observed adoption rates. Instead, our aim was to
      systematically check relevant factors that may be influencing its adoption.
      QAToCA delivers an assessment of how suitable conditions "and thus the likelihood
      for CA adoption" are. Results show that the high CA adoption potentials exhibited
      by the Malawi and Zambia case relate mostly to positive institutional factors. On
      the other hand, the low adoption potential of the Zimbabwe case, in spite of
      observed higher estimates, is attributed mainly to unstable and less secured
      market conditions for CA. In the case of Southern Burkina Faso, the potential for
      CA adoption is determined to be high, and this assessment deviates from lower
      observed figures. This is attributed mainly to strong competition of CA and
      livestock for residues in this region. Lastly, the high adoption potential found
      in Northern Burkina Faso is explained mainly by the fact that farmers here have
      no alternative other than to adopt the locally adapted CA system-Zai farming.
      Results of this assessment should help promoters of CA in the given regions to
      reflect on their activities and to eventually adjust or redesign them based on a
      more explicit understanding of where problems and opportunities are found. 

PMID- 24337195
TI  - [Early stage connective tissue diseases].

PMID- 24337196
TI  - [Early lupus erythematosus].
AB  - Early diagnosis of systemic lupus erythematosus (SLE) is a challenge even for
      experienced rheumatologists due to the heterogeneous appearance of the disease.
      The initial phase of SLE often comprises unspecific general symptoms and only few
      characteristic clinical and laboratory abnormalities in the early course.
      Seriously affected patients meet the classification criteria in early stages but
      many other affected patients do not. A concentration only on young women as
      possible new cases means that more than 50 % of all persons affected will not be
      identified. Therapy is mainly guided by the type and severity of symptoms. Organ
      manifestations need to be examined at each presentation because there is a high
      possibility for modification in the course of the disease especially in the early
      stages. Early intervention should prevent increasing damage. Key elements of
      medical treatment are antimalarial agents. Furthermore, control of co-morbidities
      and optimization of lifestyle are crucial.

PMID- 24337197
TI  - [The road to early diagnosis of systemic sclerosis : the evolution of diagnostic
      and classification criteria in the past decades].
AB  - Increasing knowledge about the rare disease systemic sclerosis (SSc) and improved
      diagnostic methods in recent decades has led to the possibility of diagnosing
      systemic sclerosis in earlier disease stages. In this review, we describe the
      evolution of diagnostic and classification criteria for SSc, beginning with the
      preliminary ARA criteria for the classification of SSc in 1980, then presenting
      the criteria for limited and diffuse cutaneous SSc by LeRoy et al. in 1988 and
      2001, and finishing with a discussion of the recently published new ACR-EULAR
      classification criteria in 2013. In addition, we seize the ongoing discussion
      about the intermediate subtype of SSc and highlight whether the two special
      subtypes CREST syndrome as well as SSc sine scleroderma are similar or different
      from the limited cutaneous SSc subtype. Finally, we address the question when a
      patient should be referred to the rheumatologist and discuss potential red flags
      for early diagnosis of systemic sclerosis. 

PMID- 24337199
TI  - [Early symptoms of dermatomyositis and antisynthetase syndrome].
AB  - INTRODUCTION: The early diagnosis of rheumatic diseases is becoming increasingly
      important. This particularly includes inflammatory myopathies which are
      multisystemic disorders with visceral involvement that are associated with high
      morbidity and mortality. Early diagnosis before the development of irreversible
      organ involvement is, therefore, of great importance. METHODS: This report
      provides information on early signs and symptoms of dermatomyositis and
      antisynthetase syndrome. Furthermore, screening methods which allow early
      diagnosis including involvement of internal organs are discussed. In addition,
      clinical and serological subtypes and their impact on prognosis are described.

PMID- 24337198
TI  - [Therapeutic management in early disease stages of systemic sclerosis : early
      diagnosis - early symptoms - early problems].
AB  - Increasing knowledge about the rare disease systemic sclerosis and improved
      diagnostic methods in the course of recent decades has led to the possibility of
      diagnosing systemic sclerosis at earlier disease stages. However, earlier
      diagnosis has an impact on routine clinical care of affected patients, and
      rheumatologists need to know about early symptoms, their diagnosis, and clinical
      management. In this review, the therapeutic management of early disease stages is
      described. In particular, we focus on diagnostic tools which should be included
      in a "basic assessment" of systemic sclerosis and discuss the diagnosis and
      treatment options of early symptoms such as Raynaud phenomenon, puffy fingers and
      hand edema, digital ulcers, calcinosis cutis, and cardiopulmonary, renal, and
      gastrointestinal involvement. Finally, the options of early immunosuppressive
      treatment and autologous stem cell transplantation for patients with rapid
      progressive and severe disease are reviewed. 

PMID- 24337200
TI  - [Infection-induced reactive arthritis : etiopathogenesis, clinical spectrum,
      therapy].
AB  - Reactive arthritis is an inflammatory joint disease induced by a preceding,
      sometimes asymptomatic bacterial infection outside the joints. With an estimated
      prevalence of 40/100,000 inhabitants, the disease primarily affects adults
      between the ages of 20 and 40 years. The clinical presentation is typically
      characterized by monoarthritis to oligoarthritis of the lower extremities with
      possible accompanying enthesitis, bursitis, tenosynovitis, sacroiliitis,
      dactylitis and rare extra-articular manifestations. Because of the similar
      clinical symptoms and an association with HLA-B27, reactive arthritis is
      attributed to the spondyloarthropathies. Typical triggering pathogens are
      Chlamydia, Salmonella, Yersinia, Shigella and Campylobacter. In about 20% of the
      cases the usually self-limiting disease becomes chronic. The pathogenesis is not
      yet understood in detail but it is currently assumed that the intracellular
      persistence of the pathogen causes an immune reaction resulting in arthritis.
      Common international diagnostic criteria do not yet exist; therefore the
      diagnosis is made largely on the basis of clinical findings, medical history and
      the direct and/or indirect pathogen detection. Several therapeutic options are
      used to treat reactive arthritis. Ongoing extra-articular infections, with the
      exception of enteritis should be treated with antibiotics. Besides symptom
      orientated treatment of acute arthritis, in prolonged and chronic reactive
      arthritis an immunomodulatory therapy with steroids, sulfasalazine or
      methotrexate is used. The role of long-term antibiotic therapy for eradication of
      persistent intra-articular pathogens in chronic cases is the subject of current
      research.

PMID- 24337202
TI  - Retraction. Millimeter wave treatment induces apoptosis via activation of the
      mitochondrial-dependent pathway in human osteo-sarcoma cells.

PMID- 24337201
TI  - [Stromal cells as coordinators of adaptive immune response and immunological
      memory].
AB  - The Greek term stroma literally means in translation mattress, covering or bed.
      In the medical context this describes the connective tissue framework of an organ
      which is composed of the stromal cells and the extracellular matrix components
      which are produced by these cells. According to the original definition stromal
      cells have a non-hematopoietic origin and adherently grow in cell culture.
      Nowadays the term is used to cover a heterogeneous group of connective tissue
      cells of mesenchymal origin which includes fibroblasts, reticular stromal cells
      and endothelial cells as well as tissue-specific connective tissue cells, such as
      osteoblasts and adipocytes. Because the stromal cells in the various tissues are
      very different with respect to morphology and functional characteristics, the
      manifold aspects of the individual stromal cell populations are now just
      beginning to be understood. This article presents a summary of new knowledge on
      the various functions of stromal cells in the immune response. 

PMID- 24337204
TI  - [Medicinal therapy and course control of glaucoma. Options and limits of local
      therapy].

PMID- 24337203
TI  - Protease activity at invadopodial focal digestive areas is dependent on NHE1
      driven acidic pHe.
AB  - Degradation of the extracellular matrix (ECM) is a critical step of tumor cell
      invasion and requires protease-dependent proteolysis focalized at the invadopodia
      where the proteolysis of the ECM occurs. Most of the extracellular proteases
      belong to serine- or metallo-proteases and the invadopodia is where protease
      activity is regulated. While recent data looking at global protease activity in
      the growth medium reported that their activity and role in invasion is dependent
      on Na+/H+ exchanger 1 (NHE1)-driven extracellular acidification, there is no data
      on this aspect at the invadopodia, and an open question remains whether this acid
      extracellular pH (pHe) activation of proteases in tumor cells occurs
      preferentially at invadopodia. We previously reported that the NHE1 is expressed
      in breast cancer invadopodia and that the NHE1-dependent acidification of the
      peri-invadopodial space is critical for ECM proteolysis. In the present study,
      using, for the first time, in situ zymography analysis, we demonstrated a
      concordance between NHE1 activity, extracellular acidification and protease
      activity at invadopodia to finely regulate ECM digestion. We demonstrated that:
      (i) ECM proteolysis taking place at invadopodia is driven by acidification of the
      peri-invadopodia microenvironment; (ii) that the proteases have a functional pHe
      optimum that is acidic; (iii) more than one protease is functioning to digest the
      ECM at these invadopodial sites of ECM proteolysis; and (iv) lowering pHe or
      inhibiting the NHE1 increases protease secretion while blocking protease activity
      changes NHE1 expression at the invadopodia.

PMID- 24337205
TI  - [Medicinal glaucoma therapy. What can we learn from large randomized clinical
      trials?].
AB  - The prospective multicenter randomized controlled clinical trials (RCTs) Ocular
      Hypertension Glaucoma Treatment Study (OHTS), Early Manifest Glaucoma Trial
      (EMGT), Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial
      Glaucoma Treatment Study (CITGS) and Collaborative Normal Tension Glaucoma Study
      (CNGTS) are often named as landmarks for glaucoma management as the results of
      these studies provided the evidence for numerous therapeutic decisions in
      clinical practice. The studies confirmed the consensus that reduction of
      intraocular pressure reduces the risk of glaucoma progression covering the whole
      spectrum of glaucoma from ocular hypertension to advanced glaucoma. Furthermore,
      the identification of new risk factors allows a higher precision of assessment of
      the risk of progression. The RCTs achieved the main goal of high level of
      evidence, thus making progress in the understanding of glaucoma and its treatment
      and bridging consensus-based and evidence-based decisions. However, the
      implementation of the results into clinical practice needs adequate and accurate
      interpretation of the results. 

PMID- 24337206
TI  - [General substance classification and pharmacology of glaucoma].
AB  - The pharmaceutical therapy of glaucoma dates back to 1875 when Weber introduced
      pilocarpine into the medicinal treatment of glaucoma. Since then there has been a
      continuous development of topical antiglaucoma therapy whereby the main
      developments date back to the 1980s and 1990s. All forms of medicinal therapy aim
      at lowering the intraocular pressure and achieve this either by inhibiting
      aqueous humor secretion into the ciliary body or by enhancing physiological
      drainage routes along Schlemm's canal. This article gives an overview over the
      most important classes of antiglaucoma drugs, the indications and
      contraindications as well as pharmacological characteristics. The focus lies on
      the market of combination and generic drug preparations that is currently rapidly
      developing and therefore needs to be discussed in detail. 

PMID- 24337207
TI  - [Recommendations for assessment of twilight vision and glare sensitivity for safe
      driving].

PMID- 24337208
TI  - [Characteristic movement disorders in myasthenic eye muscle paralysis].

PMID- 24337209
TI  - [Acanthamoeba keratitis].
AB  - The typical clinical appearance of acanthamoeba keratitis includes
      pseudodendritic epitheliopathy, perineuritis, ring infiltrates or multifocal
      stromal infiltrates and in some cases limbitis with infiltration of the
      conjunctiva and/or sterile anterior uveitis. In 83-93 % of cases of acanthamoeba
      keratitis the patients were contact lens wearers. Acanthamoeba keratitis is
      diagnosed by polymerase chain reaction (PCR), confocal biomicroscopy, in vitro
      cultivation and histopathological examination. Information on reliability and
      efficacy of conservative and surgical therapy of acanthamoeba keratitis has only
      been published in case series but not yet verified through randomized controlled
      clinical studies. After early diagnosis acanthamoeba keratitis can often be
      successfully treated using triple topical therapy with polyhexamide, propamidine
      isethionate and neomycin. Topical therapy should be continued for up to 1 year.
      In therapy-resistant cases cryotherapy, amniotic membrane transplantation,
      crosslinking therapy and therapeutic keratoplasty can be performed. The prognosis
      of keratoplasty following acanthamoeba keratitis is more favorable if there were
      no signs of infection at least 3 months before surgery. 

PMID- 24337210
TI  - Reflections on a range of cardiovascular issues.

PMID- 24337211
TI  - Endothelial nitric oxide synthase levels and their response to exercise in
      patients with slow coronary flow.
AB  - BACKGROUND: Endothelial dysfunction plays a key role in the aetiopathogenesis of
      slow coronary flow (SCF) even if there is no obstructive epicardial lesion.
      Reduced plasma levels of endothelial nitric oxide synthase (eNOS) are an
      important indicator of endothelial dysfunction. We aimed to determine plasma
      levels of eNOS and their relationship with exercise in patients with SCF.
      METHODS: Twenty-two patients with SCF in at least one coronary artery and 17
      healthy individuals were included in this study. The TIMI frame count method was
      used to determine SCF. Plasma levels of eNOS before and after effort were
      determined in the patient and control groups. RESULTS: Basal eNOS levels in the
      patient group were lower than in the control group (p = 0.040), and plasma eNOS
      levels after exercise decreased more significantly in the patient group compared
      to the control group (p = 0.002). Median decreases of eNOS in response to
      exercise were higher in the SCF group than in the control group (p < 0.001), and
      the decrease observed in the control group was not statistically significant (p =
      0.35). There were significantly negative correlations between TIMI frame count
      and plasma levels of eNOS at baseline and after exercise (r = -0.51, p = 0.015, r
      = -0.58, p = 0.005, respectively). Moreover, there was also a positive
      correlation between the rate-pressure product and plasma levels of eNOS after
      exercise in patients with SCF (r = 0.494, p = 0.019). CONCLUSION: Our findings
      indicate an important pathophysiological relationship between the severity of SCF
      in which endothelial dysfunction plays a role in its pathogenesis and the level
      of circulating plasma levels of eNOS.

PMID- 24337212
TI  - Vitamin E and antioxidant activity; its role in slow coronary flow.
AB  - AIM: Oxidative stress, which is widely recognised as an important feature of many
      diseases, can be defined as an increased formation of reactive oxygen species or
      decreased antioxidant defense. In this study we measured plasma vitamin E levels
      and total antioxidant activity (AOA) in patients with slow coronary flow (SCF).
      METHODS: The plasma vitamin E levels and AOA were measured in 40 patients with
      angiographically diagnosed SCF. Forty subjects with normal coronary flow (NCF)
      served as the control group. SCF and NCF were analysed, and blood samples were
      taken for plasma vitamin E levels and AOA. Plasma vitamin E levels and AOA in
      patients with SCF were evaluated and compared to those of patients with NCF.
      RESULTS: There was no significant difference between the two groups in terms of
      plasma AOA, lipid profile and C-reactive protein (CRP) levels but there was a
      significant difference in vitamin E levels between the two groups (p = 0.001).
      CONCLUSION: Vitamin E levels were found to be lowered in patients with SCF
      compared to the NCF group. The association between smoking and vitamin E levels
      is worth further investigating in larger samples.

PMID- 24337213
TI  - ASSAf recognises top South African scientists.

PMID- 24337214
TI  - Comparison of one- and two-stage basilic vein transposition for arterio-venous
      fistula formation in haemodialysis patients: preliminary results.
AB  - OBJECTIVE: This study aimed to compare the results of one-and two-stage basilic
      vein transposition (BVT) in haemodialysis patients. METHODS: This was a non
      randomised, retrospective study between January 2007 and January 2012 on 96
      patients who were diagnosed with end-stage renal failure (ESRF) (54 males, 42
      females; mean age 43.6 +/- 14 years) and underwent one- or two-stage BVT in our
      clinic. All patients who were not eligible for a native radio-cephalic or brachio
      cephalic arterio-venous fistula (AVF) were scheduled for one- or two-stage BVT
      after arterial (brachial, radial and ulnar) and venous (basilic and cephalic)
      Doppler ultrasonography. Patients were retrospectively divided into two groups:
      group 1, basilic vein diameter > 3 mm and patients who underwent one-stage BVT;
      and group 2, basilic vein diameter < 3 mm and patients who underwent two-stage
      BVT. In group 1, the basilic vein with a single incision was anastomosed to the
      brachial artery, followed by superficialisation. In group 2, the basilic vein was
      anastomosed to the brachial artery and they underwent the superficialisation
      procedure one month postoperatively. Fistula maturation and postoperative
      complications were assessed. RESULTS: The mean diameter of the basilic vein was
      statistically significantly higher in group 1 (3.46 +/- 0.2 mm) than in group 2
      (2.79 +/- 0.1 mm) (p < 0.05). In terms of postoperative complications,
      thrombosis, haemorrhage and haematoma were significantly higher in group 1 (34,
      36 and 17%, respectively) than in group 2 (23, 14 and 6%, respectively) (p <
      0.05). The rate of fistula maturation was significantly lower in group 1 (66%),
      compared to group 2 (77%) (p < 0.05).Time to fistula maturation was significantly
      shorter in group 1 (mean 41 +/- 14 days), compared to group 2 (mean 64 +/- 28
      days) (p < 0.05). CONCLUSION: Two-stage BVT was superior to one-stage BVT due to
      its lower rate of postoperative complications and higher fistula maturation,
      despite its disadvantage of late fistula use. Although the diameter of the
      basilic vein was larger in patients who underwent one-stage BVT, we observed that
      one-stage BVT was disadvantageous in terms of postoperative complications and
      fistula maturation.

PMID- 24337216
TI  - Chloroform fraction of Scutellaria barbata D. Don promotes apoptosis and
      suppresses proliferation in human colon cancer cells.
AB  - Scutellaria barbata D. Don (SB) has long been used as a major component in
      numerous Chinese medical formulas to clinically treat various types of cancer.
      Previously, we reported that the extracts of SB were able to suppress colon
      cancer growth in vivo and in vitro, possibly by inducing cancer cell apoptosis
      and inhibiting cell proliferation and tumor angiogenesis. However, the anticancer
      mechanisms of its bioactive ingredients remain largely unclear. In the present
      study, using three human colon cancer cell lines SW620, HT-29 and HCT-8, the
      antitumor effect of different solvent fractions of SB were evaluated and the
      potential underlying molecular mechanisms were investigated. Using an 3-(4, 5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, it was revealed that
      the chloroform fraction of SB (ECSB) exhibited the most potent inhibitory effect
      on the growth of all three colon cancer cell lines and SW620 cells exhibited the
      most sensitive response to ECSB treatment (IC50=65 ug/ml). In addition, by
      performing fluorescence-activated cell sorting, transmission electron microscopy
      and colony formation assays, it was observed that ECSB significantly induced
      apoptosis and inhibited proliferation in SW620 cells in a dose-dependent manner.
      Furthermore, ECSB treatment resulted in the upregulation of the pro-apoptotic
      Bax/Bcl-2 ratio and a decrease in the expression of the pro-proliferative cyclin
      D1 and cyclin-dependent kinase 4. The results from the present study may provide
      a scientific foundation for the development of novel anticancer agents from the
      bioactive ingredients in the ECSB.

PMID- 24337215
TI  - The ADVANCE cardiovascular risk model and current strategies for cardiovascular
      disease risk evaluation in people with diabetes.
AB  - PURPOSE: To critically examine existing approaches to cardiovascular disease
      (CVD) risk evaluation in people with diabetes, and discuss the use of accurate
      and validated absolute CVD risk tools as an appropriate basis for CVD prevention
      in people with diabetes. METHODS: This was a narrative review using evidence from
      the ADVANCE study and all relevant publications identified via PubMed MEDLINE.
      RESULTS: There is sufficient evidence that diabetes does not confer a CVD risk
      equivalent to that in non-diabetic people with existing CVD in all circumstances.
      In people with diabetes, CVD risk follows a gradient. Reliably capturing this
      gradient depends on an adequate combination of several risk factors. Many global
      CVD risk tools applicable to people with diabetes have been developed. Those
      derived from older cohorts are less accurate in contemporary populations and many
      newer tools have not been tested. The ADVANCE risk engine, recently developed
      from the large multinational ADVANCE study, showed acceptable performance on the
      ADVANCE population and largely outperformed the popular Framingham risk equation
      when tested on the multinational DIAB-HYCAR cohort of people with type 2
      diabetes. CONCLUSION: The high-risk status conferred by diabetes does not
      preclude estimation of absolute CVD risk using tools such as the ADVANCE risk
      engine and its use as the basis for initiating and intensifying CVD preventative
      measures. Adopting such an accurate and validated tool will likely improve
      prescriptions and outcomes of diabetes care.

PMID- 24337217
TI  - Sex differences in the incidence of chronic myeloid leukemia.
AB  - The incidence of chronic myeloid leukemia (CML), which is caused by BCR/ABL
      chimeric oncogene formation in a pluripotent hematopoietic stem cell (HSC),
      increases with age and exposure to ionizing radiation. CML is a comparatively
      well-characterized neoplasm, important for its own sake and useful for insights
      into other neoplasms. Here, Surveillance, Epidemiology and End Results (SEER) CML
      data are analyzed after considering possible misclassification of chronic myelo
      monocytic leukemia as CML. For people older than 25 years, plots of male and
      female CML log incidences versus age at diagnosis are approximately parallel
      straight lines with males either above or to the left of females. This is
      consistent with males having a higher risk of developing CML or a shorter latency
      from initiation to diagnosis of CML. These distinct mechanisms cannot be
      distinguished using SEER data alone. Therefore, CML risks among male and female
      Japanese A-bomb survivors are also analyzed. The present analyses suggest that
      sex differences in CML incidence more likely result from differences in risk than
      in latency. The simplest but not the sole interpretation of this is that males
      have more target cells at risk to develop CML. Comprehensive mathematical models
      of CML could lead to a better understanding of the role of HSCs in CML and other
      preleukemias that can progress to acute leukemia.

PMID- 24337218
TI  - [Hybrid operation theatre from the point of view of cardiac surgery. The future
      for the heart team].
AB  - Nowadays, increasing numbers of procedures jointly conducted by cardiac surgeons
      and cardiologists are performed as minimally invasive surgical procedures or
      interventions. Transcatheter aortic valve implantation, endovascular aortic
      aneurysm repair and a large variety of hybrid procedures for congenital heart
      disease have become current standards. Some of these hybrid procedures were shown
      to improve the therapeutic safety and efficacy, effects particularly true for
      high-risk patients and complex interventions. Hybrid procedures require indirect
      imaging, commonly provided by an angiography system in the hybrid operation
      theatre. This article describes the technical prerequisites required for a hybrid
      operation theatre as well as indications and rationales for hybrid procedures
      conducted in this environment. It is likely that the indications for
      cardiovascular hybrid procedures will continue to be expanded and that the hybrid
      operation theatre may become a laboratory for developing innovative approaches in
      the cardiovascular field. Therefore, the hybrid operation theatre will not only
      be the working environment for hybrid surgeons and interventionalists but also
      help to evolve their future. 

PMID- 24337219
TI  - [Hybrid operation theatre in vascular surgery. Options and perspectives].
AB  - BACKGROUND: Demographic development leads to an increase in vascular
      interventions due to the increase in elderly and multimorbid patients. The aim of
      this study was to demonstrate the open interventional therapy options and their
      influence on staff and patients which have become possible due to the
      introduction of angio-hybrid operations including 3-D imaging Dyna-CT. MATERIAL
      AND METHODS: The modifications with respect to radiation protection for staff,
      improvements for patients and the possibilities of operative 3-D imaging Dyna-CT
      are described based on the current literature. RESULTS: The implementation of
      angio-hybrid operation theaters has resulted in new open interventional treatment
      options which can also be employed for high risk elderly patients with aortic and
      peripheral arterial pathologies. With hybrid operations the radiation exposure
      and contrast medium exposure can be reduced for patients and an improvement in
      the results can also be achieved. The implementation of 3-D imaging in the angio
      hybrid operation theater could also lead to further improvements, especially for
      complex aortic procedures. DISCUSSION: Using angio-hybrid operational procedures
      complex interventions can be carried out with more safety for patients and
      personnel. The implementation of 3-D imaging Dyna-CT offers additional
      interesting options for complex aortic procedures.

PMID- 24337221
TI  - [Anastomotic techniques for the gastrointestinal tract].
AB  - The correct suture technique for anastomoses of the gastrointestinal (GI) tract
      is a major task in the daily practice of surgery and a basic requirement for a
      successful operation. This article provides an overview of the surgical
      principles and techniques involved in the creation of intestinal anastomoses,
      including the differentiated use of various suturing aids in the GI tract. Hand
      sewn and stapled anastomotic techniques are illustrated and discussed. The
      ongoing discussion and question as to which technique is best for GI anastomoses
      remains unanswered as there is no obligatory standard, even though the
      requirements are well defined. An ideal anastomosis should fulfil the following
      criteria: it must be well vascularized, safe, tension-free and spillage from the
      operation field should be avoided. 

PMID- 24337220
TI  - [Intraoperative neuromonitoring in thyroid surgery. Recommendations of the
      Surgical Working Group for Endocrinology].

PMID- 24337222
TI  - Atmospheric methane removal by methane-oxidizing bacteria immobilized on porous
      building materials.
AB  - Biological treatment using methane-oxidizing bacteria (MOB) immobilized on six
      porous carrier materials have been used to mitigate methane emission. Experiments
      were performed with different MOB inoculated in building materials at high (~20 %
      (v/v)) and low (~100 ppmv) methane mixing ratios. Methylocystis parvus in
      autoclaved aerated concrete (AAC) exhibited the highest methane removal rate at
      high (28.5 +/- 3.8 MUg CH4 g-1 building material h-1) and low (1.7 +/- 0.4 MUg
      CH4 g-1 building material h-1) methane mixing ratio. Due to the higher volume of
      pores with diameter >5 MUm compared to other materials tested, AAC was able to
      adsorb more bacteria which might explain for the higher methane removal observed.
      The total methane and carbon dioxide-carbon in the headspace was decreased for
      65.2 +/- 10.9 % when M. parvus in Ytong was incubated for 100 h. This study
      showed that immobilized MOB on building materials could be used to remove methane
      from the air and also act as carbon sink.

PMID- 24337223
TI  - In silico prediction and in vitro identification of bluetongue virus 4 VP5
      protein B-cell epitopes.
AB  - VP5, the outer capsid protein of bluetongue virus (BTV), plays an important role
      in viral penetration and antibody-mediated viral neutralization. Therefore, VP5
      represents an important target for development of vaccines and diagnostic tests.
      In this study, we use bioinformatic tools to predict nine antigenic B cell
      epitopes in the VP5 protein of a BTV serotype 4 (BTV4) isolate from China.
      Further, we generate five BTV4 VP5-specific monoclonal antibodies (MAbs) and
      define their corresponding epitopes using a set of VP5-derived peptides expressed
      as maltose-binding protein (MBP) fusion proteins. The five identified epitopes
      map to amino acids 119-134, 257-272, 286-301, 322-337, and 481-496 of the VP5
      protein. Importantly, the epitopes identified using VP5-derived peptides do not
      correlate with our bioinformatic prediction of antibody epitopes. Identification
      and characterization of BTV4 VP5 protein epitopes may aid the development of
      diagnostic tools and provide information with which to study the structure of the
      BTV VP5 protein.

PMID- 24337224
TI  - Changes in physician antipsychotic prescribing preferences, 2002-2007.
AB  - OBJECTIVE: Physician antipsychotic prescribing behavior may be influenced by
      comparative effectiveness evidence, regulatory warnings, and formulary and other
      restrictions on these drugs. This study measured changes in the degree to which
      physicians are able to customize treatment choices and changes in physician
      preferences for specific agents after these events. METHODS: The study used 2002
      2007 prescribing data from the IMS Health Xponent database and data on physician
      characteristics from the American Medical Association for a longitudinal cohort
      of 7,399 physicians. Descriptive and multivariable regression analyses were
      conducted of the concentration of prescribing (physician-level Herfindahl index)
      and preferences for and likelihood of prescribing two first-generation
      antipsychotics and six second-generation antipsychotics. Analyses adjusted for
      prescribing volume, specialty, demographic characteristics, practice setting, and
      education. RESULTS: Antipsychotic prescribing was highly concentrated at the
      physician level, with a mean unadjusted Herfindahl index of .33 in 2002 and .29
      in 2007. Psychiatrists reduced the concentration of their prescribing more over
      time than did other physicians. High-volume psychiatrists had a Herfindahl index
      that was half that of low-volume physicians in other specialties (.18 versus
      .36), a difference that remained significant (p<.001) after adjustment for
      physician characteristics. The share of physicians preferring olanzapine dropped
      from 29.9% in 2002 to 10.3% in 2007 (p<.001) while the share favoring quetiapine
      increased from 9.4% to 44.5% (p<.001). Few physicians (<5%) preferred a first
      generation antipsychotic in 2002 or 2007. CONCLUSIONS: Preferences for specific
      antipsychotics changed dramatically during this period. Although physician
      prescribing remained heavily concentrated, the concentration decreased over time,
      particularly among psychiatrists.

PMID- 24337225
TI  - Remembrance of things future.

PMID- 24337228
TI  - Numerical simulation of vertebral artery stenosis treated with different stents.
AB  - We sought to investigate the effects of endovascular stents with different links
      for treating stenotic vertebral artery and to determine the relationship between
      the shape of the link and in-stent restenosis (ISR). We also attempted to provide
      scientific guidelines for stent design and selection for clinical procedures.
      Models of three types of stent with different links (L-stent, V-stent, and S
      stent) and an idealized stenotic vertebral artery were established. The
      deployment procedure for the stent in the stenotic vertebral artery was simulated
      for solid mechanics analysis. Next, the deformed models were extracted to
      construct the blood flow domain, and numerical simulations of the hemodynamics in
      these models were performed using the finite element method. The numerical
      results demonstrated that: (1) Compared with the L-stent and V-stent, the S-stent
      has a better flexibility and induces less stress in the stent strut. Furthermore,
      less stress is generated in the arterial wall. (2) Vascular straightening is
      scarcely influenced by the shape of the link, but it is closely related to the
      flexibility of the stent. (3) The S-stent has the smallest foreshortening among
      the three types of stents. (4) Compared with the V-stent and S-stent, the L-stent
      causes a smaller area with low wall shear stress, less blood stagnation area, and
      better blood flow close to the artery wall. From the viewpoint of the combination
      of solid mechanics and hemodynamics, the S-stent has better therapeutic effects
      because of its lower potential for inducing ISR and its better prospects in
      clinical applications compared with the L-stent and V-stent.

PMID- 24337227
TI  - H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated
      by the upregulation of COX-2/PGI2.
AB  - The hypoxia-induced proliferation of pulmonary artery smooth muscle cells
      (PASMCs) is the main cause of pulmonary arterial hypertension (PAH), in which
      oxidative stress, cyclooxygenase (COX)-2 and hydrogen sulfide (H(2)S) all play an
      important role. In the present study, we aimed to examine the effects of H(2)S on
      the hypoxia-induced proliferation of human PASMCs (HPASMCs) and to elucidate the
      underlying mechanisms. The HPASMCs were treated with cobalt chloride (CoCl(2)), a
      hypoxia-mimicking agent, to establish a cellular model of hypoxic PAH. Prior to
      treatment with CoCl(2), the cells were pre-conditioned with sodium hydrosulfide
      (NaHS), a donor of H(2)S. Cell proliferation, reactive oxygen species (ROS)
      production, COX-2 expression, prostacyclin (also known as prostaglandin I2 or
      PGI(2)) secretion and H(2)S levels were detected in the cells. The exposure of
      the HPASMCs to CoCl(2) markedly increased cell proliferation, accompanied by a
      decrease in COX-2 expression, PGI(2) secretion and H(2)S levels; however, the
      levels of ROS were not altered. Although the exogenous ROS donor, H(2)O(2),
      triggered similar degrees of proliferation to CoCl(2), the ROS scavenger, N
      acetyl-L-cysteine (NAC), markedly abolished the H(2)O(2)-induced cell
      proliferation, as opposed to the CoCl(2)-induced proliferation. The CoCl(2)
      induced proliferation of HPASMCs was suppressed by exogenously applied PGI(2).
      The addition of H(2)S (NaHS) attenuated the CoCl(2)-induced cell proliferation
      through the increase in the intercellular content of H(2)S. Importantly, the
      exposure of the cells to H(2)S suppressed the CoCl(2)-induced downregulation in
      COX-2 expression and PGI(2) secretion from the HPASMCs. In conclusion, the
      results from the current study suggest that H(2)S enhances hypoxia-induced cell
      proliferation through the upregulation of COX-2/PGI(2), as opposed to ROS.

PMID- 24337229
TI  - Tactile localization depends on stimulus intensity.
AB  - Few experimental data are available about the influence of stimulus intensity on
      localization of cutaneous stimuli. The localization behavior of an individual as
      function of the veridical stimulus sites can be represented in the form of a
      perceptual map. It is unknown how the intensity of cutaneous stimuli influences
      these perceptual maps. We investigated the effect of stimulus intensity on trial
      to-trial localization variability and on perceptual maps. We applied non-painful
      electrocutaneous stimuli of three different intensities through seven surface
      electrodes on the lower arm of healthy participants. They localized the stimuli
      on a tablet monitor mounted directly above their arm, on which a photograph of
      this arm was presented. The length of the arm over which the stimuli were
      localized was contracted when compared to the real electrode positions. This
      length increased toward veridical with increasing stimulus intensity. The trial
      to-trial variance of the localizations dropped significantly with increasing
      intensity. Furthermore, localization biases of individual stimulus positions were
      shown to decrease with increasing stimulus intensity. We conclude that tactile
      stimuli are localized closer to veridical with increasing intensity in two
      respects: the localizations become more consistent and more accurate. 

PMID- 24337230
TI  - Laugh yourself to sleep: memory consolidation for humorous information.
AB  - There is extensive evidence that emotional information is better remembered than
      neutral information across long delays, especially if the delay interval contains
      an opportunity for sleep. However, as prior studies have focused on memory for
      negative stimuli, it is unclear whether positive memories benefit from time and
      sleep as well. To investigate the consolidation of positive memories, the current
      study examined differences in memory for humorous and non-humorous cartoons.
      While prior evidence demonstrates that humorous information is preferentially
      remembered relative to non-humorous information over brief delays, it is unknown
      whether this benefit lasts across longer delay intervals or whether sleep is
      important for lasting humor memories to form. Thus, we tested memory for 27
      cartoons across 12-h delay periods containing either sleep or wakefulness.
      Results indicate that humor's enhancing effect on recall memory is robust across
      a 12-h delay and that a period of sleep facilitates this effect over wakefulness
      when cartoons are novel to participants and ranked based on subjective emotional
      ratings. Further, in accordance with previous studies that reveal diminished
      emotional reactivity to stimuli following sleep, in a supplemental experiment, we
      found that sleep reduced subjective ratings of humor, arousal, and positivity of
      humorous cartoons. These findings provide preliminary evidence that sleep's
      impact on negative emotional memory consolidation and emotional reactivity can be
      extended to positive stimuli as well. 

PMID- 24337231
TI  - Effects of sleep stage and sleep episode length on the alerting, orienting, and
      conflict components of attention.
AB  - Awakening from different sleep stages, percentage of different stages of sleep
      subsumed within a sleep episode, and sleep episode length, have all been
      hypothesized to affect cognitive performance upon awakening. To further examine
      the contribution of these factors, 14 healthy participants slept for 3 h (0300
      0600 hours) and 6 h (2400-0600 hours), with each sleep episode separated by 1
      week. Electroencephalographic measures were taken throughout each sleep episode,
      and participants completed the Attentional Network Test, which measures alerting,
      orienting, and executive functioning (conflict) components of attention, upon
      awakening. Overall, mean reaction time (RT) was slower in the 3- and 6-h post
      sleep conditions than in a baseline (pre-sleep) condition. Alerting, orienting,
      and conflict measures of attention did not significantly differ across the
      baseline and two post-sleep conditions. Awakening from REM sleep resulted in
      slower overall RT than awakening from lighter sleep (stages 1 and 2). In multiple
      regression analyses, overall RT was predicted by the duration of slow wave sleep
      (SWS), such that more time spent in SWS was associated with an overall slowing of
      RT. Conflict scores were predicted by the duration of REM; that is, more time
      spent in REM was associated with greater amounts of conflict (i.e., larger
      flanker effects). These data provide more information about the process of
      awakening and suggest that SWS and REM influence different aspects of attention
      upon awakening.

PMID- 24337232
TI  - Good vibrations? Vibrotactile self-stimulation reveals anticipation of body
      related action effects in motor control.
AB  - Previous research suggests that motor actions are intentionally generated by
      recollecting their sensory consequences. Whereas this has been shown to apply to
      visual or auditory consequences in the environment, surprisingly little is known
      about the contribution of immediate, body-related consequences, such as
      proprioceptive and tactile reafferences. Here, we report evidence for a
      contribution of vibrotactile reafferences to action selection by using a response
      effect compatibility paradigm. More precisely, anticipating actions to cause
      spatially incompatible vibrations delayed responding to a small but reliable
      degree. Whereas this observation suggests functional equivalence of body-related
      and environment-related reafferences to action control, the future application of
      the described experimental procedure might reveal functional peculiarities of
      specific types of sensory consequences in action control.

PMID- 24337233
TI  - Computed tomography morphometric analysis of C2 translaminar screw fixation of
      Wright's technique and a modified technique in the pediatric cervical spine.
AB  - PURPOSE: To establish reference data on the dimensions of C2 lamina to guide the
      use of translaminar screws with Wright's technique and a modified technique for
      pediatric patients in different age groups. METHODS: 113 pediatric patients were
      divided into six age groups, and their cervical vertebrae were studied on CT
      scans. Laminar height, width, length and screw angle were measured. Statistical
      analysis was performed using Student t tests, Pearson's correlation and linear
      regression analysis. RESULTS: Mean laminar height was 10.95 +/- 2.81 mm, and mean
      width was 6.01 +/- 0.90 mm. For Wright's technique, mean laminar length was 30.65
      +/- 3 mm, and the screw angle was 56.02 degrees  +/- 3.62 degrees . For the
      modified technique, mean laminar length was 22.07 +/- 2.38 mm, and the screw
      angle was 67.40 degrees  +/- 3.39 degrees . 95.6% (108/113) of the children could
      insert a screw into the lamina (laminar width >= 4.5 mm), 72.6% (82/113) could
      accept bilateral translaminar screws (laminar width >= 4.5 mm and laminar height
      >= 9 mm). CONCLUSION: Our investigation provides insight into the anatomy of C2
      lamina in six pediatric age groups. Compared to adults, the benefits of C2
      translaminar screws fixation are more obvious in the pediatric spine which has a
      large C2 lamina. Compared to Wright's technique, the modified technique should
      insert a screw with bigger insert angle and shorter screw length.

PMID- 24337234
TI  - A multimarker qPCR platform for the characterisation of endometrial cancer.
AB  - The molecular background of endometrial cancer (EC) has not been fully
      elucidated. In the present study, we developed a quantitative PCR (qPCR) platform
      to examine the gene dosages of the potential molecular markers MGB1, TOP2A, ERBB1
      4, MYC, CCND1, ESR1 and PI3K. The platform was applied in samples collected from
      157 EC patients (stage I-IV) to verify its clinical utility and to examine the
      diagnostic and prognostic significance of the analysed biomarkers. The gene
      dosage pattern of the ERBB family and its downstream effectors PI3K and MYC
      showed particularly strong correlations with clinicopathological data. The ERBB
      PI3K/Akt pathway was upregulated in 31 (20%) of 156 cases. Activation of the ERBB
      PI3K/Akt pathway was positively correlated with a higher stage (p=0.001), higher
      grade (p=0.001), histological type II disease (p=0.0003) and metastases (p=0.02).
      The implemented hierarchical clustering revealed that cluster 2 was characterised
      by high copy numbers of the studied genes. Cluster 2 was associated with shorter
      overall survival (p=0.05). The platform was found to be a fast and simple method
      for direct analysis of the genes involved in uterine carcinogenesis, making it
      feasible for EC biology characterisation.

PMID- 24337235
TI  - Effect of cold storage and freezing on the biomechanical properties of swine
      growth plate explants.
AB  - Ex vivo biomechanical testing of growth plate samples provides essential
      information about its structural and physiological characteristics. Experimental
      limitations include the preservation of the samples since working with fresh
      tissues involves significant time and transportation costs. Little information is
      available on the storage of growth plate explants. The aim of this study was to
      determine storage conditions that could preserve growth plate biomechanical
      properties. Porcine ulnar growth plate explants (n = 5 per condition) were stored
      at either 4  degrees C for periods of 1, 2, 3, and 6 days or frozen at -20 
      degrees C with slow or rapid sample thawing. Samples were tested using stress
      relaxation tests under unconfined compression to assess five biomechanical
      parameters. The maximum compressive stress (sigmamax) and the equilibrium stress
      (sigmaeq) were directly extracted from the experimental curves, while the fibril
      network reinforced biphasic model was used to obtain the matrix modulus (Em), the
      fibril modulus (Ef), and the permeability (k). No significant changes were
      observed in sigmaeq and Em in any of the tested storage conditions. Significant
      decreases and increases, respectively, were observed in sigmamax and k in the
      growth plate samples refrigerated for more than 48 h and in the frozen samples,
      when compared with the fresh samples. The fibril modulus Ef of all stored samples
      was significantly reduced compared to the fresh samples. These results indicate
      that the storage of growth plates in a humid chamber at 4  degrees C for a
      maximum of 48 h is the condition that minimizes the effects on the measured
      biomechanical parameters, with only Ef significantly reduced. Refrigerating
      growth plate explants for less than 48 h maintains their maximal stress,
      equilibrium stress, matrix modulus, and permeability. However, cold storage at 4 
      degrees C for more than 48 h and freezing storage at -20  degrees C significantly
      alter the biomechanical response of growth plate samples. Appropriate growth
      plate sample storage will be beneficial to save time and reduce transportation
      costs to pick up fresh samples.

PMID- 24337236
TI  - Regionalized differentiation of CRH, TRH, and GHRH peptidergic neurons in the
      mouse hypothalamus.
AB  - According to the updated prosomeric model, the hypothalamus is subdivided
      rostrocaudally into terminal and peduncular parts, and dorsoventrally into alar,
      basal, and floor longitudinal zones. In this context, we examined the ontogeny of
      peptidergic cell populations expressing Crh, Trh, and Ghrh mRNAs in the mouse
      hypothalamus, comparing their distribution relative to the major progenitor
      domains characterized by molecular markers such as Otp, Sim1, Dlx5, Arx, Gsh1,
      and Nkx2.1. All three neuronal types originate mainly in the peduncular
      paraventricular domain and less importantly at the terminal paraventricular
      domain; both are characteristic alar Otp/Sim1-positive areas. Trh and Ghrh cells
      appeared specifically at the ventral subdomain of the cited areas after E10.5.
      Additional Ghrh cells emerged separately at the tuberal arcuate area,
      characterized by Nkx2.1 expression. Crh-positive cells emerged instead in the
      central part of the peduncular paraventricular domain at E13.5 and remained
      there. In contrast, as development progresses (E13.5-E18.5) many alar Ghrh and
      Trh cells translocate into the alar subparaventricular area, and often also into
      underlying basal neighborhoods expressing Nkx2.1 and/or Dlx5, such as the tuberal
      and retrotuberal areas, becoming partly or totally depleted at the original birth
      sites. Our data correlate a topologic map of molecularly defined hypothalamic
      progenitor areas with three types of specific neurons, each with restricted
      spatial origins and differential migratory behavior during prenatal hypothalamic
      development. The study may be useful for detailed causal analysis of the
      respective differential specification mechanisms. The postulated migrations also
      contribute to our understanding of adult hypothalamic complexity. 

PMID- 24337237
TI  - Insular and caudate lesions release abnormal yawning in stroke patients.
AB  - Abnormal yawning is an underappreciated phenomenon in patients with ischemic
      stroke. We aimed at identifying frequently affected core regions in the
      supratentorial brain of stroke patients with abnormal yawning and contributing to
      the anatomical network concept of yawning control. Ten patients with acute
      anterior circulation stroke and >=3 yawns/15 min without obvious cause were
      analyzed. The NIH stroke scale (NIHSS), Glasgow Coma Scale (GCS), symptom onset,
      period with abnormal yawning, blood oxygen saturation, glucose, body temperature,
      blood pressure, heart rate, and modified Rankin scale (mRS) were assessed for all
      patients. MRI lesion maps were segmented on diffusion-weighted images, spatially
      normalized, and the extent of overlap between the different stroke patterns was
      determined. Correlations between the period with abnormal yawning and the
      apparent diffusion coefficient (ADC) in the overlapping regions, total stroke
      volume, NIHSS and mRS were performed. Periods in which patients presented with
      episodes of abnormal yawning lasted on average for 58 h. Average GCS, NIHSS, and
      mRS scores were 12.6, 11.6, and 3.5, respectively. Clinical parameters were
      within normal limits. Ischemic brain lesions overlapped in nine out of ten
      patients: in seven patients in the insula and in seven in the caudate nucleus.
      The decrease of the ADC within the lesions correlated with the period with
      abnormal yawing (r = -0.76, Bonferroni-corrected p = 0.02). The stroke lesion
      intensity of the common overlapping regions in the insula and the caudate nucleus
      correlates with the period with abnormal yawning. The insula might be the long
      sought-after brain region for serotonin-mediated yawning. 

PMID- 24337238
TI  - [Antibiotic prophylaxis in dermatologic and soft tissue surgery].
AB  - In Germany, over half a million operations are done in dermatologic surgery in a
      hospital setting every year, as well as a less well quantified number of
      procedures in private offices. In spite of this large number, specific guidelines
      concerning the use of perioperative antibiotics in dermatologic surgery are
      sparse. In contrast to procedures in general, visceral or gynecological surgery,
      general guidelines on perioperative antibiotics issued by the Paul-Ehrlich
      Institutes and the AWMF do not specifically consider dermatologic operations.
      Several surveys indicate that familiarity with current recommendations on
      perioperative antibiotics is suboptimal and resulted in a considerable overuse of
      perioperative antibiotics in dermatologic surgery. Given the increasing
      antimicrobial resistance among important pathogens and the inherent risks of
      antibiotic administration, the decision for the use of prophylactic antibiotics
      should be based on the individual risk profile of the patient and of the surgical
      procedure. In the following, we will critically discuss the evidence for
      perioperative antibiotics in dermatologic surgery. 

PMID- 24337239
TI  - [Cutaneous leishmaniasis. Diagnosis and therapy in northern Afghanistan].
AB  - BACKGROUND: The German S1 guidelines from 2009 contain a variety of
      recommendations for the treatment of cutaneous leishmaniasis. PATIENTS AND
      METHODS: We report the results of our diagnostic procedures and treatment of 32
      international patients in autumn 2010 in northern Afghanistan. RESULTS: Giemsa
      stain confirmed the clinical diagnosis within 24 hours. Eleven simple lesions and
      one larger ulcer responded well to cryotherapy and intralesional sodium
      stibogluconate. More complex lesions in 19 patients responded well to oral
      miltefosine. One patient refused outpatient therapy. CONCLUSIONS: Cryotherapy and
      intralesional antimony compounds showed good results in early lesions of
      cutaneous leishmaniasis in northern Afghanistan. Outpatient treatment of complex
      lesions with miltefosine was successful in all cases.

PMID- 24337240
TI  - Outcome of negative-pressure wound therapy for open abdomen treatment after
      nontraumatic lower gastrointestinal surgery: analysis of factors affecting
      delayed fascial closure in 101 patients.
AB  - BACKGROUND: Few studies have focused on the risk factors for failure to achieve
      fascial closure after use of negative-pressure wound therapy (NPWT) in an open
      abdomen (OA). We aimed at analyzing possible risk factors for failure of fascial
      closure and the risk of fistulas after nontrauma lower gastrointestinal (GI)
      tract surgery treated with OA. METHODS: This retrospective study included 101
      nontrauma patients treated with OA from 2007 to 2011. Multivariate analyses of
      risk factors were performed. RESULTS: Indications for OA were diffuse peritonitis
      (n = 47), need for second look (n = 26), failure to achieve fascial closure
      (e.g., bowel edema) at primary laparotomy (n = 24), and fascial necrosis (n = 4).
      Of the 101 patients, 61 (60 %) were alive at discharge, with one death possibly
      related to OA (fistula from an iatrogenic perforation). Delayed fascial closure
      was obtained in 40 (66 %) of the surviving patients, with 80 % when the
      indications for OA was need for second look and 72 % in cases of diffuse
      peritonitis. Compared with need for second look [hazard ratio (HR = 1), 95 % CI],
      proportional HR for failure of delayed fascial closure were peritonitis 1.96
      (1.10-3.49) and failure to achieve fascial closure at primary laparotomy 4.70
      (2.17-10.2). In the presence of a stoma the HR was 2.02 (1.13-3.63). CONCLUSIONS:
      OA using NPWT seems to be a safe procedure, with few procedure-related
      complications. Failure of fascial closure is related to the indication of OA and
      the presence of a stoma. Prospective multicenter studies are needed to establish
      which patients with lower GI surgery benefit from OA.

PMID- 24337241
TI  - Candidates for limited lateral neck dissection among patients with metastatic
      papillary thyroid carcinoma.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) is associated with an excellent
      prognosis but frequently spreads to regional lymph nodes. The extent of neck
      dissection, particularly routine level II or V lymphadenectomy, is still
      controversial as it may lead to spinal accessory nerve injury and associated
      postoperative morbidities. We assessed the diagnostic value of preoperative
      ultrasonography (US) plus computed tomography (CT) for detecting metastatic lymph
      nodes and for identifying predictors of level II or V metastasis in patients with
      PTC. METHODS: The results of US and CT were compared with histopathologic
      findings at various neck levels in 209 previously untreated PTC patients with
      lateral cervical nodal metastases who underwent total thyroidectomy with central
      and lateral neck dissection. Clinicopathologic predictors for level II or V
      metastases were identified. RESULTS: Pathologic metastases to level II and V were
      observed in 53.6 and 25.4 % of patients, respectively. Occult metastases were
      found in 34.5 and 16.8 %, respectively. The sensitivities of US plus CT for
      levels II and V were 64.6 and 50.9 %, respectively. Image-based, isolated lateral
      level IV involvement and macroscopic extranodal extension were independently
      associated with level II metastasis or either level II or V metastasis (p <
      0.01). Macroscopic extranodal extension was also independently associated with
      level V metastasis (p = 0.001). CONCLUSIONS: Patients with image-based, isolated
      lateral level IV involvement and no macroscopic extranodal extension are
      potential candidates for limited level III-IV dissection or prophylactic level II
      lymphadenectomy omission. Level V lymphadenectomy may be omitted in patients
      without macroscopic extranodal extension.

PMID- 24337242
TI  - Kounis syndrome leads to cardiogenic shock.
AB  - Kounis syndrome has been defined as an acute coronary syndrome that manifests as
      unstable vasospastic or nonvasospastic angina, and even as acute myocardial
      infarction. It is triggered by the release of inflammatory mediators following an
      allergic insult or patient ill health, drug intake or environmental exposure. We
      report on a patient who was admitted to our hospital and diagnosed with unstable
      angina or acute myocardial infarction - according to analytical parameters,
      electrocardiographic abnormalities, and/or coronary angiography - in the context
      of progesterone as inducing factor. The results of a laboratory study revealed
      electrocardiogram changes, and increased myocardial enzymes, IgE antibodies and
      eosinophils. The patient experienced recurring chest pain, acute myocardial
      infarction, and cardiogenic shock after taking progesterone capsules; her
      medication history of progesterone clearly correlated with the onset of chest
      pain, which suggested that the cause of the vasospasm may have been related to
      progesterone use. We did not include patients with a history of bronchial asthma
      or allergic constitution. Nevertheless, the case suggests there is a correlation
      between Kounis syndrome and progesterone as inducing factor. 

PMID- 24337243
TI  - Mini-sternotomy approach for aortic valve replacement in a patient with
      osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a heritable disorder of the connective tissue.
      Cardiovascular involvement is rare, related mainly to aortic valve regurgitation.
      Open-heart surgery in these patients is associated with increased morbidity and
      mortality rates as a result of tissue friability and bone brittleness as well as
      platelet dysfunction. We present a patient with OI who underwent successful
      aortic valve replacement with a mini-sternotomy approach. 

PMID- 24337244
TI  - Antiphospholipid syndrome in a young Nigerian girl presenting with gangrenous
      toes.
AB  - We report on a 21-year-old Nigerian girl with toe gangrene, which is one of the
      most unlikely forms of presentation of antiphospholipid syndrome among Africans.
      The essence of this case report is to raise awareness that, although
      antiphospholipid syndrome typically presents in Africans in association with a
      pregnancy-related event or a neuropathology, it should be considered as a
      differential diagnosis in all African patients with unexplained vasculitis. A
      high index of suspicion and early treatment will prevent toe amputations and
      reduce mortality rates. 

PMID- 24337245
TI  - A female with X-linked Alport syndrome and compound heterozygous COL4A5
      mutations.
AB  - BACKGROUND: Female subjects with X-linked Alport syndrome have a single COL4A5
      mutation, germ cell mosaicism in affected tissues and typically develop renal
      failure later or less often than male subjects. Women with two mutations are
      exceedingly rare, and usually have consanguineous parents or uniparental disomy.
      We describe here a 20-year-old woman who inherited two different COL4A5 variants,
      one from her father (c.2677G>C) and one from her mother (c.384 +1 G>A). CASE
      DIAGNOSIS/TREATMENT: The index case had normal renal function, proteinuria and no
      clinically detectable hearing loss, or ocular abnormalities. Her father and
      paternal uncle developed end-stage renal disease at 37 and 28 years respectively,
      together with hearing loss, but not lenticonus or central retinopathy. Her mother
      had mildly impaired renal function, proteinuria, hearing loss, but no ocular
      abnormalities. Her maternal grandfather and 22-year-old brother, both with this
      mutation, developed renal failure by 28 years with hearing loss, or had
      proteinuria and hearing loss respectively. CONCLUSION: The index case has
      clinical features consistent with germ cell mosaicism of two COL45A mutations
      associated with adult-onset renal failure, but no ocular abnormalities. Her risk
      of renal failure is high, but the rate of progression to end-stage disease
      depends on the underlying mutations, and disease modification with renin
      angiotensin blockade.

PMID- 24337248
TI  - [Secondary lens implantation: Part 1: A continuously current topic].

PMID- 24337247
TI  - Nephrin and Podocin functions are highly conserved between the zebrafish
      pronephros and mammalian metanephros.
AB  - The slit diaphragm (SD) is a highly specialized intercellular junction between
      podocyte foot processes and is crucial in the formation of the filtration barrier
      in the renal glomeruli. Zebrafish Nephrin and Podocin are important in the
      formation of the podocyte SD and mutations in NEPHRIN and PODOCIN genes cause
      human nephrotic syndrome. In the present study, the zebrafish Podocin protein was
      observed to be predominantly localized in the pronephric glomerular podocytes, as
      previously reported for Nephrin. To understand the function of Podocin and
      Nephrin in zebrafish, splice-blocking morpholino antisense oligonucleotides were
      used. Knockdown of Podocin or Nephrin by this method induced pronephric
      glomerular hypoplasia with pericardial edema. Human Nephrin and Podocin mRNA
      rescued this glomerular phenotype, however, the efficacy of the rescues was
      greatly reduced when mRNA-encoding human disease-causing NEPHRIN-R1109X and
      PODOCIN-R138Q were used. Furthermore, an association between zebrafish Nephrin
      and Podocin proteins was observed. Notably, Podocin-R150Q, corresponding to human
      PODOCIN-R138Q, markedly interacted with Nephrin compared with wild-type Podocin,
      suggesting that this strong binding capacity of mutated Podocin impairs the
      transport of Nephrin and Podocin out of the endoplasmic reticulum. The results
      suggest that the functions of Nephrin and Podocin are highly conserved between
      the zebrafish pronephros and mammalian metanephros. Accordingly, the zebrafish
      pronephros may provide a useful tool for analyzing disease-causing gene mutations
      in human kidney disorders. 

PMID- 24337249
TI  - Integrated microbial processes for biofuels and high value-added products: the
      way to improve the cost effectiveness of biofuel production.
AB  - The production of microbial biofuels is currently under investigation, as they
      are alternative sources to fossil fuels, which are diminishing and their use has
      a negative impact on the environment. However, so far, biofuels derived from
      microbes are not economically competitive. One way to overcome this bottleneck is
      the use of microorganisms to transform substrates into biofuels and high value
      added products, and simultaneously taking advantage of the various microbial
      biomass components to produce other products of interest, as an integrated
      process. In this way, it is possible to maximize the economic value of the whole
      process, with the desired reduction of the waste streams produced. It is expected
      that this integrated system makes the biofuel production economically sustainable
      and competitive in the near future. This review describes the investigation on
      integrated microbial processes (based on bacteria, yeast, and microalgal
      cultivations) that have been experimentally developed, highlighting the
      importance of this approach as a way to optimize microbial biofuel production
      process. 

PMID- 24337246
TI  - Epigenetic landscape for initiation of DNA replication.
AB  - The key genetic process of DNA replication is initiated at specific sites
      referred to as replication origins. In eukaryotes, origins of DNA replication are
      not specified by a defined nucleotide sequence. Recent studies have shown that
      the structural context and topology of DNA sequence, chromatin features, and its
      transcriptional activity play an important role in origin choice. During
      differentiation and development, significant changes in chromatin organization
      and transcription occur, influencing origin activity and choice. In the last few
      years, a number of different genome-wide studies have broadened the understanding
      of replication origin regulation. In this review, we discuss the epigenetic
      factors and mechanisms that modulate origin choice and firing. 

PMID- 24337250
TI  - Enhanced production of poly(lactate-co-3-hydroxybutyrate) from xylose in
      engineered Escherichia coli overexpressing a galactitol transporter.
AB  - Poly(lactate-co-3-hydroxybutyrate) (P(LA-co-3HB)) was previously produced from
      xylose in engineered Escherichia coli. The aim of this study was to increase the
      polymer productivity and LA fraction in P(LA-co-3HB) using two metabolic
      engineering approaches: (1) deletions of competing pathways to lactate production
      and (2) overexpression of a galactitol transporter (GatC), which contributes to
      the ATP-independent xylose uptake. Engineered E. coli mutants (DeltapflA,
      Deltapta, DeltaackA, DeltapoxB, Deltadld, and a dual mutant; DeltapflA +
      Deltadld) and their parent strain, BW25113, were grown on 20 g l(-1) xylose for
      P(LA-co-3HB) production. The single deletions of DeltapflA, Deltapta, and
      Deltadld increased the LA fraction (58-66 mol%) compared to BW25113 (56 mol%). In
      particular, the DeltapflA + Deltadld strain produced P(LA-co-3HB) containing 73
      mol% LA. Furthermore, GatC overexpression increased both polymer yields and LA
      fractions in DeltapflA, Deltapta, and Deltadld mutants, and BW25113. The
      DeltapflA + gatC strain achieved a productivity of 8.3 g l(-1), which was 72 % of
      the theoretical maximum yield. Thus, to eliminate limitation of the carbon
      source, higher concentration of xylose was fed. As a result, BW25113 harboring
      gatC grown on 40 g l(-1) xylose reached the highest P(LA-co-3HB) productivity of
      14.4 g l(-1). On the other hand, the DeltapflA + Deltadld strain grown on 30 g l(
      1) xylose synthesized 6.4 g l(-1) P(LA-co-3HB) while maintaining the highest LA
      fraction (73 mol%). The results indicated the usefulness of GatC for enhanced
      production of P(LA-co-3HB) from xylose, and the gene deletions to upregulate the
      LA fraction in P(LA-co-3HB). The polymers obtained had weight-averaged molecular
      weights in the range of 34,000-114,000.

PMID- 24337251
TI  - The attractive recombinant phytase from Bacillus licheniformis: biochemical and
      molecular characterization.
AB  - The phyL gene encoding phytase from the industrial strain Bacillus licheniformis
      ATCC 14580 (PhyL) was cloned, sequenced, and overexpressed in Escherichia coli.
      Biochemical characterization demonstrated that the recombinant enzyme has an
      apparent molecular weight of nearly 42 kDa. Interestingly, this enzyme was
      optimally active at 70-75  degrees C and pH 6.5-7.0. This enzyme is
      distinguishable by the fact that it preserved more than 40 % of its activity at
      wide range of temperatures from 4 to 85  degrees C. This new phytase displayed
      also a high specific activity of 316 U/mg. For its maximal activity and
      thermostability, this biocatalyst required only 0.6 mM of Ca(2+) ion and
      exhibited high catalytic efficiency of 8.3 s(-1) MUM(-1) towards phytic acid. 

PMID- 24337252
TI  - Production of recombinant Chikungunya virus envelope 2 protein in Escherichia
      coli.
AB  - Chikungunya, a mosquito-borne viral disease caused by Chikungunya virus (CHIKV),
      has drawn substantial attention after its reemergence causing massive outbreaks
      in tropical regions of Asia and Africa. The recombinant envelope 2 (rE2) protein
      of CHIKV is a potential diagnostic as well as vaccine candidate. Development of
      cost-effective cultivation media and appropriate culture conditions are generally
      favorable for large-scale production of recombinant proteins in Escherichia coli.
      The effects of medium composition and cultivation conditions on the production of
      recombinant Chikungunya virus E2 (rCHIKV E2) protein were investigated in shake
      flask culture as well as batch cultivation of Escherichia coli. Further, the fed
      batch process was also carried out for high cell density cultivation of E. coli
      expressing rE2 protein. Expression of rCHIKV E2 protein in E. coli was induced
      with 1 mM isopropyl-beta-thiogalactoside (IPTG) at ~23 g dry cell weight (DCW)
      per liter of culture and yielded an insoluble protein aggregating to form
      inclusion bodies. The final DCW after fed-batch cultivation was ~35 g/l. The
      inclusion bodies were isolated, solubilized in 8 M urea and purified through
      affinity chromatography to give a final product yield of ~190 mg/l. The
      reactivity of purified E2 protein was confirmed by Western blotting and enzyme
      linked immunosorbent assay. These results show that rE2 protein of CHIKV may be
      used as a diagnostic reagent or for further prophylactic studies. This approach
      of producing rE2 protein in E. coli with high yield may also offer a promising
      method for production of other viral recombinant proteins.

PMID- 24337253
TI  - Comparison of CO-dependent H2 production with strong promoters in Thermococcus
      onnurineus NA1.
AB  - To overproduce biotechnologically valuable products, the expression level of
      target genes has been modulated by using strong promoters. In a hyperthermophilic
      archaeon Thermococcus onnurineus NA1, two promoters, P(TN0413) and P(TN0157),
      which drive expression of the genes encoding the S-layer protein and glutamate
      dehydrogenase were inserted in front of a gene cluster encoding a carbon monoxide
      dehydrogenase, a hydrogenase and a Na+/H+ antiporter. Two promoters exhibited
      strong activity by increasing the transcription and translation levels of the
      gene cluster in the mutant strains by 2.5- to 49-folds and 1.4- to 3.3-folds,
      respectively, than the native promoter in the wild-type strain. While KS0413 with
      P(TN0413) promoter exhibited 2.7 to 4.7 times higher transcript level than KS0157
      with P(TN0157) promoter, the levels of proteins were a little different between
      them. The biomass concentrations and H2 production rates of two mutants were 2-
      to 3-fold higher than those of the wild-type strain in a bioreactor where CO was
      supplied at a flow rate of 120 ml min-1. Two mutants showed differential response
      to the higher CO flow rate, 240 ml min-1, in terms of growth pattern and product
      formation, indicating two promoters were regulated by culture conditions. The
      results demonstrate that not only promoter strength but also product-forming
      conditions should be considered in promoter engineering.

PMID- 24337254
TI  - Effect of carnitine, acetyl-, and propionylcarnitine supplementation on the body
      carnitine pool, skeletal muscle composition, and physical performance in mice.
AB  - PURPOSE: Pharmacokinetics and effects on skeletal muscle and physical performance
      of oral acetylcarnitine and propionylcarnitine are not well characterized. We
      therefore investigated the influence of oral acetylcarnitine, propionylcarnitine,
      and carnitine on body carnitine homeostasis, energy metabolism, and physical
      performance in mice and compared the findings to non-supplemented control
      animals. METHODS: Mice were supplemented orally with 2 mmol/kg/day carnitine,
      acetylcarnitine, or propionylcarnitine for 4 weeks and studied either at rest or
      after exhaustive exercise. RESULTS: In the supplemented groups, total plasma and
      urine carnitine concentrations were significantly higher than in the control
      group receiving no carnitine, whereas the skeletal muscle carnitine content
      remained unchanged. The supplemented acylcarnitines were hydrolyzed in intestine
      and liver and reached the systemic circulation as carnitine. Bioavailability of
      carnitine and acylcarnitines, determined as the urinary excretion of total
      carnitine, was in the range of 19 %. Skeletal muscle morphology, including fiber
      type composition, was not affected, and oxygen consumption by soleus or
      gastrocnemius fibers was not different between the groups. Supplementation with
      carnitine or acylcarnitines had no significant impact on the running capacity,
      but was associated with lower plasma lactate levels and a higher glycogen content
      in white skeletal muscle after exhaustive exercise. CONCLUSIONS: Oral
      supplementation of carnitine, acetylcarnitine, or propionylcarnitine in mice is
      associated with increased plasma and urine total carnitine concentrations, but
      does not affect the skeletal muscle carnitine content. Despite better
      preservation of skeletal muscle glycogen and lower plasma lactate levels,
      physical performance was not improved by carnitine or acylcarnitine
      supplementation.

PMID- 24337255
TI  - Posture and movement classification: the comparison of tri-axial accelerometer
      numbers and anatomical placement.
AB  - Patient compliance is important when assessing movement, particularly in a free
      living environment when patients are asked to don their own accelerometers.
      Reducing the number of accelerometers could increase patient compliance. The aims
      of this study were (1) to determine and compare the validity of different
      accelerometer combinations and placements for a previously developed posture and
      dynamic movement identification algorithm. Custom-built activity monitors, each
      containing one tri-axial accelerometer, were placed on the ankles, right thigh,
      and waist of 12 healthy adults. Subjects performed a protocol in the laboratory
      including static orientations of standing, sitting, and lying down, and dynamic
      movements of walking, jogging, transitions between postures, and fidgeting to
      simulate free-living activity. When only one accelerometer was used, the thigh
      was found to be the optimal placement to identify both movement and static
      postures, with a misclassification error of 10%, and demonstrated the greatest
      accuracy for walking/fidgeting and jogging classification with sensitivities and
      positive predictive value (PPVs) greater than 93%. When two accelerometers were
      used, the waist-thigh accelerometers identified movement and static postures with
      greater accuracy than the thigh-ankle accelerometers (with a misclassification
      error of 11% compared to 17%). However, the thigh-ankle accelerometers
      demonstrated the greatest accuracy for walking/ fidgeting and jogging
      classification with sensitivities and PPVs greater than 93%. Movement can be
      accurately classified in healthy adults using tri-axial accelerometers placed on
      one or two of the following sites: waist, thigh, or ankle. Posture and
      transitions require an accelerometer placed on the waist and an accelerometer
      placed on the thigh. 

PMID- 24337256
TI  - Specialized service use for psychiatric and neurodevelopmental disorders by age
      14 in Finland.
AB  - OBJECTIVE: Most studies on the diagnostic patterns of usage of specialized
      services for childhood psychiatric and neurodevelopmental disorders have been
      cross-sectional, and the aim of this study was to provide longitudinal data.
      METHODS: The Medical Birth Register and the Finnish Hospital Discharge Register
      were used to study the use of inpatient or public outpatient specialized services
      for psychiatric and neurodevelopmental disorders between birth and age 14 in 2010
      (cumulative incidence) and in year 2010 at age 14 (one-year prevalence) among
      Finnish children born in 1996 (N=58,538 singleton live births). RESULTS: The
      cumulative incidence of specialized service use for any psychiatric or
      neurodevelopmental disorders between birth and age 14 was 12.9%, and the one-year
      prevalence in 2010 at 14 years was 4.2%. The cumulative incidence by age 14 was
      5.5% for learning and coordination disorders, 2.2% for anxiety disorders, 2.0%
      for hyperkinetic disorders, 1.7% for conduct disorders, 1.4% for depression, 1.0%
      for autism spectrum disorders, and .7% for stress and adjustment disorders.
      Learning and coordination, hyperkinetic, and autism spectrum disorders were more
      prevalent among boys, were often diagnosed before school age, and had 9%-51%
      lifetime comorbidity with each other. Depressive, anxiety, and stress and
      adjustment disorders had similar distributions between the sexes, were often
      diagnosed in early adolescence, and showed 8%-31% lifetime comorbidity with each
      other. CONCLUSIONS: Every eighth Finnish child had visited specialized services
      for psychiatric or neurodevelopmental disorders sometime between birth and age
      14. Learning and coordination disorders were diagnosed more than twice as often
      as anxiety, hyperkinetic, and conduct disorders.

PMID- 24337257
TI  - A threat to a virtual hand elicits motor cortex activation.
AB  - We report an experiment where participants observed an attack on their virtual
      body as experienced in an immersive virtual reality (IVR) system. Participants
      sat by a table with their right hand resting upon it. In IVR, they saw a virtual
      table that was registered with the real one, and they had a virtual body that
      substituted their real body seen from a first person perspective. The virtual
      right hand was collocated with their real right hand. Event-related brain
      potentials were recorded in two conditions, one where the participant's virtual
      hand was attacked with a knife and a control condition where the knife only
      struck the virtual table. Significantly greater P450 potentials were obtained in
      the attack condition confirming our expectations that participants had a strong
      illusion of the virtual hand being their own, which was also strongly supported
      by questionnaire responses. Higher levels of subjective virtual hand ownership
      correlated with larger P450 amplitudes. Mu-rhythm event-related desynchronization
      in the motor cortex and readiness potential (C3-C4) negativity were clearly
      observed when the virtual hand was threatened-as would be expected, if the real
      hand was threatened and the participant tried to avoid harm. Our results support
      the idea that event-related potentials may provide a promising non-subjective
      measure of virtual embodiment. They also support previous experiments on pain
      observation and are placed into context of similar experiments and studies of
      body perception and body ownership within cognitive neuroscience.

PMID- 24337258
TI  - The role of quantitative changes in the epxression of insulin receptor substrate
      1 and nuclear ubiquitin in abnormal glycometabolism in the livers of KKay mice
      and the relative therapeutic mechanisms of Astragalus polysaccharide.
AB  - Ubiquitin and the ubiquitination pathway are important regulators of insulin
      signaling. The insulin receptor substrate-1 (IRS-1), an ubiquitin-interacting
      adaptor protein, serves as the key docking protein in insulin signaling. The
      effects of this dynamic interaction and the changes in ubiquitin expression on
      hepatic insulin signaling, as well as the relative therapeutic effects of
      Astragalus polysaccharide (APS) have not yet been elucidated. In this study, we
      aimed to investigate the abnormal changes which occur in the levels of IRS-1 and
      ubiquitin in the livers of mice (mice with insulin resistance and diabetes), and
      to elucidate the possible mechanisms responsible for these changes. A control
      group (CG), an insulin resistance group (IG) and a diabetes group (DG) were
      respectively composed of 12-week-old C57BL/6J mice fed a normal diet, C57BL/6J
      mice fed a high-fat diet and KKay mice fed a high-fat diet, and treatment groups
      were composed of corresponding groups treated with APS (CG + A, IG + A, DG + A).
      All the mice were age-matched and grouped at random. After eight weeks, the mouse
      models were successfully established and the related physiological or biochemical
      indexes were detected using corresponding methods. Ubiquitin expression in the
      liver was detected by immunohistochemisty, and western blot analysis was used to
      detect the expression of IRS-1 and ubiquitin. The results revealed that the
      expression of IRS-1 in the DG was significantly lower compared to that in the CG
      and IG; however, the nuclear expression of ubiquitin and the ubiquitination
      levels of IRS-1, including body weight and blood glucose and triglyceride levels
      in the DG were significantly higher compared to those in the CG or IG (P<0.05).
      There was a significant improvement in the ubiquitination levels in DG + A,
      including the blood glucose and triglyceride levels compared with the DG
      (P<0.05). From the stage of insulin resistance to the stage of diabetes, the
      reduced expression of IRS-1 and its enhanced ubiquitination levels combined with
      the overexpression of nuclear ubiquitin contributed to the abnormal
      glycometabolism and the disruption of insulin signaling. APS showed beneficial
      effects, such as lowering body weight, as well as blood glucose and triglyceride
      levels, and these effects correlated with the downregulation of the
      ubiquitination levels of IRS-1 and the nuclear expression of ubiquitin.

PMID- 24337259
TI  - Suppression of 2,4-dinitrochlorobenzene-induced atopic dermatitis by extract of
      Bacillus Calmette-Guerin.
AB  - Bacillus Calmette-Guerin extract (BCGE) has been proven to be clinically
      effective for anaphylactic disease, infectious diseases and cancer. In this
      study, we investigated the effect of the intramuscular application of BCGE on 2,4
      dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). We established an AD
      model in BALB/c mice by repeated local exposure of DNCB to the ear and dorsal
      skin. Following intramuscular application of BCGE, the ear thickness, mast cell
      infiltration, serum total immunoglobulin E (IgE) and histamine level were
      measured. In addition, levels of interleukin (IL)-4, IL-13, interferon (IFN)
      gamma and tumor necrosis factor (TNF)-alpha in the ears were assayed. BCGE
      reduced AD symptoms based on ear thickness, dermatitis score, histopathological
      analysis and serum IgE levels. In addition, BCGE inhibited mast cell infiltration
      into the ear and elevation of serum histamine, increased IFN-gamma level and
      suppressed IL-4, IL-13 and TNF-alpha levels in the ears. Furthermore, BCGE
      attenuated the NF-kappaBp65 expression in the nuclear extract of the ear tissue.
      Taken together, our results demonstrated that intramuscular application of BCGE
      exerts beneficial effects on the symptoms of AD suggesting that BCGE may be a
      candidate for the treatment of AD. 

PMID- 24337260
TI  - Orienting movements in area 9 identified by long-train ICMS.
AB  - The effect of intracortical microstimulation has been studied in several cortical
      areas from motor to sensory areas. The frontal pole has received particular
      attention, and several microstimulation studies have been conducted in the
      frontal eye field, supplementary eye field, and the premotor ear-eye field, but
      no microstimulation studies concerning area 9 are currently available in the
      literature. In the present study, to fill up this gap, electrical
      microstimulation was applied to area 9 in two macaque monkeys using long-train
      pulses of 500-700-800 and 1,000 ms, during two different experimental conditions:
      a spontaneous condition, while the animals were not actively fixating on a visual
      target, and during a visual fixation task. In these experiments, we identified
      backward ear movements, goal-directed eye movements, and the development of head
      forces. Kinematic parameters for ear and eye movements overlapped in the
      spontaneous condition, but they were different during the visual fixation task.
      In this condition, ear and eye kinematics have an opposite behavior: movement
      amplitude, duration, and maximal and mean velocities increase during a visual
      fixation task for the ear, while they decrease for the eye. Therefore, a top-down
      visual attention engagement could modify the kinematic parameters for these two
      effectors. Stimulation with the longest train durations, i.e., 800/1,000 ms,
      evokes not only the highest eye amplitude, but also a significant development of
      head forces. In this research article, we propose a new vision of the frontal
      oculomotor fields, speculating a role for area 9 in the control of goal-directed
      orienting behaviors and gaze shift control. 

PMID- 24337261
TI  - Reading the bones.

PMID- 24337266
TI  - Astronomy. Lick Observatory in trouble as austerity starts to bite.

PMID- 24337267
TI  - Planetary science. New results send Mars rover on a quest for ancient life.

PMID- 24337268
TI  - Pharmaceuticals. Advocates protest the cost of a hepatitis C cure.

PMID- 24337269
TI  - Ancient DNA. Fossilized teeth offer mouthful on ancient microbiome.

PMID- 24337270
TI  - Evolution. Cavefish study supports controversial evolutionary mechanism.

PMID- 24337271
TI  - Astronomy. Europe readies peerless star mapper.

PMID- 24337272
TI  - The thousand-year graveyard.

PMID- 24337273
TI  - Stefan Behnisch and the good client.

PMID- 24337274
TI  - Health information and the like.

PMID- 24337275
TI  - Health information and the like--response.

PMID- 24337276
TI  - Setting the course for a green Internet.

PMID- 24337277
TI  - Finding best practices for fossil fuel extraction.

PMID- 24337279
TI  - Ethics. The bioethics commission on incidental findings.

PMID- 24337280
TI  - Climate change. What role for short-lived climate pollutants in mitigation
      policy?

PMID- 24337282
TI  - Applied physics. Colloid science collides with liquid crystals.

PMID- 24337281
TI  - Evolution. The hidden codes that shape protein evolution.

PMID- 24337283
TI  - Genetics. My oldest sister is a sea walnut?

PMID- 24337284
TI  - Microbiology. An enzymatic route to H2 storage.